PMID- 24110221
TI  - A new device for the care of Congenital Central Hypoventilation Syndrome patients
      during sleep.
AB  - Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disease that
      causes an autonomous nervous system dysregulation. Patients are unable to have a
      correct ventilation, especially during sleep, facing risk of death. Therefore,
      most of them are mechanically ventilated during night and their blood oxygenation
      is monitored, while a supervisor keeps watch over them. If low oxygen levels are
      detected by the pulse-oximeter, an alarm fires; the supervisor deals with the
      situation and, if there is neither a technical problem nor a false alarm, wakes
      the subject, as CCHS patients usually recover from hypoxia when roused from
      sleep. During a single night multiple alarms may occur, causing fractioned sleep
      for the subject and a lasting state of anxiety for supervisors. 

PMID- 24110223
TI  - Measurement of radioactivity concentration in blood by using newly developed ToT
      LuAG-APD based small animal PET tomograph.
AB  - In order to obtain plasma time activity curve (PTAC), input function for almost
      all quantitative PET studies, patient blood is sampled manually from the artery
      or vein which has various drawbacks. Recently a novel compact Time over Threshold
      (ToT) based Pr:LuAG-APD animal PET tomograph is developed in our laboratory which
      has 10% energy resolution, 4.2 ns time resolution and 1.76 mm spatial resolution.
      The measured value of spatial resolution shows much promise for imaging the blood
      vascular, i.e; artery of diameter 2.3-2.4mm, and hence, to measure PTAC for
      quantitative PET studies. To find the measurement time required to obtain
      reasonable counts for image reconstruction, the most important parameter is the
      sensitivity of the system. Usually small animal PET systems are characterized by
      using a point source in air. We used Electron Gamma Shower 5 (EGS5) code to
      simulate a point source at different positions inside the sensitive volume of
      tomograph and the axial and radial variations in the sensitivity are studied in
      air and phantom equivalent water cylinder. An average sensitivity difference of
      34% in axial direction and 24.6% in radial direction is observed when point
      source is displaced inside water cylinder instead of air.

PMID- 24110224
TI  - Parametric imaging via kinetics-induced filter for dynamic positron emission
      tomography.
AB  - Due to the noisy measurement of the voxel-wise time activity curve (TAC),
      parametric imaging for dynamic positron emission tomography (PET) is a
      challenging task. To address this problem, some spatial filters, such as Gaussian
      filter, bilateral filter, wavelet-based filter, and so on, are often performed to
      reduce the noise of each frame. However, these filters usually just consider
      local properties of each frame without exploring the kinetic information. In this
      paper, aiming to improve the quantitative accuracy of parametric imaging, we
      present a kinetics-induced filter to lower the noise of dynamic PET images by
      incorporating the kinetic information. The present kinetics-induced filter is
      designed via the similarity between voxel-wise TACs under the framework of
      bilateral filter. Experimental results with a simulation study demonstrate that
      the present kinetics-induced filter can achieve noticeable gains than other
      existing methods for parametric images in terms of quantitative accuracy
      measures. 

PMID- 24110225
TI  - A high-resolution and one-cycle conversion time-to-digital converter architecture
      for PET image applications.
AB  - In this paper, a high-resolution and one-cycle conversion time-to-digital
      converter (TDC) architecture with cell-based design for positron emission
      tomography (PET) applications is presented. The proposed TDC employs a cascade
      stage structure to achieve high timing resolution and wide sampling range at the
      same time. Besides, based on the proposed two-level conversion structure, the
      proposed TDC not only can achieve single cycle latency and high speed of
      operation, but also have low circuit complexity as compared with conventional
      approaches. Simulation results show that operation frequency of the proposed TDC
      can be improved to 200 MHz with 50 ps resolution. In addition, the proposed TDC
      can be implemented with standard cells, making it easily portable to different
      processes and very suitable for biomedical chip applications.

PMID- 24110226
TI  - A study on the artifacts generated by dental materials in PET/CT image.
AB  - PET/CT system reduces the scanning time and provides an anatomical image because
      it realizes a CT-based attenuation corrected image without using an isotope, such
      as 68 Ge or 137Cs, in the attenuation correcting method due to the recent
      technological development. On the other hand, artifacts are generated in a CT
      image by dental materials, which affect the attenuation corrected PET image.
      Against this backdrop, this study performed a clinical experiment and a phantom
      experiment. The clinical experiment targeted 40 patients without oral disease,
      including 20 patients who had metal prosthesis in their tooth and 20 patients who
      had a dental implant in tooth. In the phantom experiment, a dental cast was used
      for a PET/CT scan after the metal prosthesis and the dental implant was inserted
      in the original dental phantom to make a dental cast. According to the study
      results, when the patients had metal prosthesis, standard uptake value (SUV)
      decreased by approximately 19.6% in the dark streak artifact region and increased
      by approximately 90.1% in the bright streak artifact region, compared with the
      artifact free region. In the phantom with metal prosthesis, the SUV decreased by
      approximately 18.1% in the dark streak artifact region and increased by 18.0% in
      the bright streak artifact region, compared to the artifact free region. When the
      patients with dental implant, the SUV decreased by approximately 19.1% in the
      dark streak artifact region and increased by 96.6% in the bright streak artifact
      region, compared with the artifact free region. In the phantom with dental
      implant, the SUV decreased by approximately 14.4% in the dark streak artifact
      region and increased by 7.0% in the bright streak artifact region, compared to
      the artifact free region. Therefore, by considering these results, we can improve
      the diagnostic accuracy in oral and maxillofacial cancer.

PMID- 24110227
TI  - Discussion on the alteration of 18F-FDG uptake by the breast according to the
      menstrual cycle in PET imaging.
AB  - 18F-FDG PET/CT is a useful modality for identifying high-glucose-consuming cells,
      such as cancer cells by the glucose metabolism of FDG. FDG is taken up by cancer
      and inflammatory cells but occasionally, there is some FDG uptake on normal
      tissues as a result of their individual physiological characteristics. In
      particular, in fertile females, unusual FDG uptake in the breast changes
      according to the stages in the menstrual cycle, which can adversely affect a
      diagnosis. Therefore, this study examined the change in breast FDG uptake in the
      menstrual cycle on 18F-FDG PET/CT. One hundred and sixty females (34 +/- 3.5
      years old), who had not undergone a gynecologic anamnesis and had a regular
      menstrual cycle over the previous 6 months, were examined from March 2011 to
      February 2012. The subjects were divided into the following 4 groups (each with
      40 patients): flow phase, proliferative phase, ovulatory phase and secretory
      phase using Pregnancy Calculator 0.14 and history taking. Discovery STE (GE
      Healthcare, USA) was used as the PET/CT. The SUVs on the accumulated region on
      the breast were analyzed, and 3 nuclear medicine specialists performed a blind
      test. The SUVs on the breast were the flow phase (1.64 +/- 0.25), proliferative
      phase (0.93 +/- 0.28), ovulatory phase (1.66 +/- 0.26) and secretory phase (1.77
      +/- 0.28). Higher uptake values were observed in the secretory, flow phase and
      ovulatory phase (p< 0.05). The accumulation of the breast was divided into the
      following 3 grades compared to the lung and liver by gross analysis: the breast
      uptake was equal to the lung (Grade I); between the lung and liver (Grade II);
      and equal to or greater than the liver (Grade III). These results showed a high
      uptake value in the secretory, flow phase and ovulatory phase (p <0.05). In
      fertile females, the FDG uptake of the breast showed changes according to the
      menstrual cycle, which can be used to improve the diagnosis of breast disease.
      Therefore, the false-negative findings of breast disease can be reduced by
      performing an examination at the appropriate period through history taking and
      considering the individual menstrual cycle. 

PMID- 24110228
TI  - Defining gross tumor volume using positron emission tomography/computed
      tomography phantom studies.
AB  - Tumor volume and standard uptake value (SUV) calculated from positron emission
      tomography/computed tomography (PET/CT) images differ from their real values.
      Besides errors introduced by scintillation materials, photomultiplier tubes, and
      image reconstruction algorithms, measurements are affected by patients'
      prostheses, body movements, and body shape. To address these problems, we
      calculated tumor volume and SUV using the standard phantom (PET Phantom-NEMA
      IEC/2001) and obtained calibration constants. We found that while tumor volume
      increases with increasing SUV and tumor diameter, it also increases with
      increasing SUV and decreasing tumor diameter. Conversely, tumor volume decreases
      with decreasing SUV and tumor diameter and with decreasing SUV and increasing
      diameter. These results suggest that a correction factor should be applied to SUV
      and tumor volume obtained from PET/CT images. 

PMID- 24110229
TI  - Classification of Alzheimer's disease from FDG-PET images using favourite class
      ensembles.
AB  - Classification of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI)
      from brain images using machine learning methods has become popular. Although the
      large majority of the existing techniques rely on a single classifier such as the
      Support Vector Machine (SVM), several ensemble methods such as Adaboost or Random
      Forests (RF) have also been explored. The ensemble methods combine the outputs of
      several classifiers and aim to increase performance by exploring the diversity of
      the base classifiers in terms of features or examples, which are usually randomly
      selected. In this paper we propose using a different kind of ensemble to address
      the three class problem of classifying AD, MCI and Control Normals (CN) from PET
      brain images. We propose the favourite class ensemble of classifiers where each
      base classifier in the ensemble uses a different feature subset which is
      optimized for a given class. Since different image features correspond to
      different sets of brain voxels, the proposed favourite class classifiers are able
      to take into account the fact that the spatial pattern of brain degeneration in
      AD changes in time as the disease progresses. We tested this approach on FDG-PET
      images from The Alzheimer's Disease Neuroimaging Initiative (ADNI) database using
      as base classifiers both Support Vector Machines (SVM) and Random Forests (RF).
      The ensembles systematically outperformed the corresponding single classifier
      with the best result (66.78%) being obtained by the SVM ensemble. 

PMID- 24110230
TI  - Cardiac PET imaging of 18F-FDG metabolism: study of healthy and infarcted hearts
      of rats.
AB  - This paper, considers the evolution of a method presented previously by authors
      to correct for cross contamination effect on the dynamic image sequences and
      shows how this development allows for a robust voxel by voxel implementation
      yielding parametric images for healthy and unhealthy subjects. Our approach is
      based on the decomposition of image pixel intensity into blood and tissue
      components using Bayesian statistics. The method uses an a priori knowledge of
      the probable distribution of blood and tissue in the images. Likelihood measures
      are computed by a General Gaussian Distribution (GGD) model. Bayes' rule is then
      applied to compute weights that account for the concentrations of the radiotracer
      in blood and tissue and their relative contributions in each image pixel. We
      tested the method on a set of dynamic cardiac (18)F-fluoro-deoxy-d-glucose PET of
      healthy rats and unhealthy rats. The results show the benefit of our correction
      on the generation of parametric images of myocardial metabolic rates for glucose
      (MMRG).

PMID- 24110231
TI  - Algorithm for selecting appropriate transfer support equipment and a robot based
      on user physical ability.
AB  - In this present paper, we propose an algorithm for selecting appropriate transfer
      support equipment and robot based on the physical ability of the user. In
      addition, we describe the relationship between physical human features and the
      burden during standing when using a standing support robot. Although a number of
      care support devices have been developed, assistive robots are not yet popular
      because users do not know which devices are appropriate for their needs or
      physical abilities. In this study, we focus on a transfer support device and
      propose an algorithm for selecting transfer support equipment and a robot that
      suits the user's physical ability. We investigated the relationship between
      standing support equipment including a robot and the physical burden during
      standing, which is a basic transfer motion. Experimentally, we analyzed and
      calculated the knee and ankle joint moments and discussed the relationship
      between standing support equipment and knee and ankle joint moments during
      standing; we also investigated and the relationship between physical human
      features and the knee joint moment during standing. Our results identified
      standing support equipment that was appropriate to the user's physical ability.
      We found that it was effective to provide an up/down seat to persons having low
      residual ability; a standing support robot is appropriate for people having less
      residual ability in the knees, and a railing is suitable for people having low
      residual ability in the ankles. 

PMID- 24110232
TI  - Development of an assistive patient mobile system for hospital environments.
AB  - This paper presents an assistive patient mobile system for hospital environments,
      which focuses on transferring the patient without nursing help. The system is a
      combination of an advanced hospital bed and an autonomous navigating robot. This
      intelligent bed can track the robot and routinely navigates and communicates with
      the bed. The work centralizes in building a structure, hardware design and robot
      detection and tracking algorithms by using laser range finder. The assistive
      patient mobile system has been tested and the real experiments are shown with a
      high performance of reliability and practicality. The accuracy of the method
      proposed in this paper is 91% for the targeted testing object with the error rate
      of classification by 6%. Additionally, a comparison between our method and a
      related one is also described including the comparison of results. 

PMID- 24110233
TI  - Robot-aided motion planning for knee joint rehabilitation with two robot
      manipulators.
AB  - In this paper, we propose a simultaneous design method of motion and external
      force trajectories for knee joint rehabilitation based on the biomechanical
      analysis of the lower limb. In this method we assume to use two robots
      manipulators which provide forces and moments at shank and thigh. We developed a
      7 degree of freedom musculoskeletal model of lower limb with 19 muscles. The
      valuation function of rehabilitation efficiency e has been maximized by Genetic
      Algorithm (GA) that refers to the musculoskeletal model and tunes motion
      trajectory of the robots and forces acting on the shank and thigh. 

PMID- 24110234
TI  - Estimation of wheelchair states during movement using WELL-SphERE for evaluation
      of power wheelchair safety.
AB  - To comprehensively evaluate the usability and safety of a power wheelchair (PWC),
      monitoring multimodal data related to the PWC in a real environment is crucial.
      In most studies exploring actual wheelchair conditions, modification of PWCs has
      been required. Especially modification of controlling circuits aiming for
      measurement of joystick operation may lead to controller malfunction and thus
      increase safety risk. It is essential, therefore, to ensure the safety of PWC
      users during experiments so that they can measure PWC-related data with their own
      wheelchairs. To achieve this aim, we developed a recording device that is easily
      installed on PWCs without any electronic modifications. The device, called a
      "WELL-SphERE," has sensing units that can be attached to PWCs a data management
      unit that can store and transfer measurement data. Here, we focused on joystick
      operation logged by the system. Seven participants were pre-tested to examine the
      characteristics of logged operations during runs through four test courses.
      Subsequently, all participants completed a questionnaire regarding the difficulty
      of the test courses. From these results, we classified the logged operations into
      four categories of "wheelchair states." Two participants--a novice driver and a
      mature driver--were also evaluated to verify the accuracy of the estimated
      wheelchair states. The accuracies of the estimates by the mature and novice
      driver were 98.8% and 89.0%, respectively. The wheelchair states for both
      participants showed characteristic patterns. Therefore, the wheelchair states
      estimated with the data logged using WELL-SphERE are valid indicators of the
      wheelchair conditions during movement.

PMID- 24110235
TI  - The use of an exoskeleton to investigate the self advantage phenomenon.
AB  - This paper presents an upper extremity exoskeleton with an original application
      in neuroscience. The novelty of this study is the investigation of the self
      advantage phenomenon under various experimental conditions. Usually this kind of
      experiments lies only on human visual ability to explicitly and/or implicitly
      recognize their own arm movements. Using an exoskeleton to replay recorded
      trajectories allows to give another perspective to the previous studies in
      including the proprioceptive ability of humans. Twelve healthy subjects were
      involved in this study. The results show that the self advantage phenomenon is
      even more present in the implicit tasks. 

PMID- 24110236
TI  - The rotational axis approach for resolving the kinematic redundancy of the human
      arm in reaching movements.
AB  - The human arm is kinematically redundant with respect to reaching tasks in a 3
      dimensional (3D) workspace. Research on reaching movements of the healthy human
      arm reveals the control strategy of the human motor system, which can be further
      applied to the upper limb exoskeletons used for stroke rehabilitation.
      Experiments performed on ten healthy subjects have shown that when reaching from
      one point to another, the human arm rotates around an axis going through the
      shoulder. The proposed redundancy resolution based on the direction of the axis
      can predict the arm posture with a higher accuracy comparing to a redundancy
      resolution that maximizes the motion efficiency. It is also shown that for
      reaching movements in the comfortable arm motion range, the directions of the
      axis are constrained by a linear model. 

PMID- 24110237
TI  - UltraPulse--simulating a human arterial pulse with focussed airborne ultrasound.
AB  - Medical simulators provide a risk-free environment for trainee doctors to
      practice and improve their skills. UltraPulse is a new tactile system designed to
      utilise focussed airborne ultrasound to mimic a pulsation effect such as that of
      a human arterial pulse. In this paper, we focus on the construction of the
      haptics component, which can later be integrated into a variety of medical
      procedure training simulators. 

PMID- 24110238
TI  - A pilot biomedical engineering course in rapid prototyping for mobile health.
AB  - Rapid prototyping of medically assistive mobile devices promises to fuel
      innovation and provides opportunity for hands-on engineering training in
      biomedical engineering curricula. This paper presents the design and outcomes of
      a course offered during a 16-week semester in Fall 2011 with 11 students
      enrolled. The syllabus covered a mobile health design process from end-to-end,
      including storyboarding, non-functional prototypes, integrated circuit
      programming, 3D modeling, 3D printing, cloud computing database programming, and
      developing patient engagement through animated videos describing the benefits of
      a new device. Most technologies presented in this class are open source and thus
      provide unlimited "hackability". They are also cost-effective and easily
      transferrable to other departments. 

PMID- 24110239
TI  - Evaluation of FCS self and peer-assessment approach based on Cooperative and
      Engineering Design learning.
AB  - The Cooperative Learning in Engineering Design curriculum can be enhanced with
      structured and timely self and peer assessment teaching methodologies which can
      easily be applied to any Biomedical Engineering curriculum. A study was designed
      and implemented to evaluate the effectiveness of this structured and timely self
      and peer assessment on student team-based projects. In comparing the 'peer-blind'
      and 'face-to-face' Fair Contribution Scoring (FCS) methods, both had advantages
      and disadvantages. The 'peer-blind' self and peer assessment method would cause
      high discrepancy between self and team ratings. But the 'face-to-face' method on
      the other hand did not have the discrepancy issue and had actually proved to be a
      more accurate and effective, indicating team cohesiveness and good cooperative
      learning. 

PMID- 24110240
TI  - Low noise and high CMRR front-end amplifier dedicated to portable EEG acquisition
      system.
AB  - This paper concerns the design and implementation of a fully integrated low noise
      and high CMRR rail-to-rail preamplifier dedicated to EEG acquisition channel. The
      preamplification technique is based on two complementary CMOS True Logarithmic
      Amplifier (TLA) stages connected in parallel. The TLA largely amplifies small
      amplitude of EEG signals, and moderately the large amplitude ones created during
      epileptic. A chopper stabilization technique is used to filter the 1/f noise and
      the DC offset voltage of the input CMOS transistors and to increase the common
      mode rejection ratio (CMRR). Due to the TLA structure, a high CMRR and high power
      supply rejection ratio are achieved and the signal-to-noise ratio (of the channel
      is better enhanced). To snugly fit the ADC input window to the EEG signal
      magnitude a new programming gain approach is implemented. Also, a chopper spike
      filter is used to cancel the spike voltages generated by the charge injections of
      modulator/demodulator switches. The proposed preamplifier is implemented in 0.18
      um CMOS technology. Post-layout simulation results exhibit 253 dB @50/60 Hz as
      CMRR, 500 nVrms @100 Hz as input-referred noise while consuming 55 uA from a 1.8
      V supply. 

PMID- 24110241
TI  - Historical development of heat stroke prevention device in the military.
AB  - Understanding of core body temperature, heat stress and heat stroke developed
      progressively over the centuries. Soldiers involved in military operations have a
      higher risk to develop heat stroke, and to not survive following the onset. This
      paper follows the evolving understanding of heat stroke and development of
      counter measures. At certain times in history, incomplete understanding of the
      causes of heat stroke led to the development of devices that did not lower the
      risk. As understanding improved, development of improved methods and devices
      became possible. In the present day, several designs for garments that can lower
      core body temperature or brain temperature have been developed, and would reduce
      the risk of heat stroke. These cooling devices include a vest and collar system.
      Further refinements of these designs to make them more practical would allow
      wider deployment. 

PMID- 24110242
TI  - Oxygen saturation in children with and without obstructive sleep apnea using the
      phone-oximeter.
AB  - Obstructive sleep apnea (OSA) in children can lead to daytime sleepiness, growth
      failure and developmental delay. Polysomnography (PSG), the gold standard to
      diagnose OSA is highly resource intensive and is confined to the sleep
      laboratory. In this study we propose to identify children with OSA using blood
      oxygen saturation (SpO2) obtained from the Phone Oximeter. This portable, in-home
      device is able to monitor patients over multiple nights, causes less sleep
      disturbance and facilitates a more natural sleep pattern. The proposed algorithm
      analyzes the SpO2 signal in the time and frequency domain using a 90-s sliding
      window. Three spectral parameters are calculated from the power spectral density
      (PSD) to evaluate the modulation in the SpO2 due to the oxyhemoblobin
      desaturations. The power P, slope S in the discriminant band (DB), and ratio R
      between P and total power are calculated for each window. Tendency and
      variability indices, number of SpO2 desaturations and time spent under 2% or 3%
      of baseline saturation level are computed for each time window. The statistical
      distribution of the temporal evolution of all parameters is analyzed to identify
      68 children, 30 with OSA and 38 without OSA (nonOSA). This characterization was
      evaluated by a feature selection based on a linear discriminant. The combination
      of temporal and spectral parameters provided the best leave one out
      crossvalidation results with an accuracy of 86.8%, a sensitivity of 80.0%, and a
      specificity of 92.1% using only 5 parameters. The median of R, mean of P and S
      and mean and standard deviation of the number of desaturations below 3% of
      baseline saturation level, were the most representative parameters. Hence, a
      better knowledge of SpO2 dynamics could help identifying children with OSA with
      the Phone Oximeter. 

PMID- 24110243
TI  - An unsupervised method for on-chip neural spike detection in multi-electrode
      recording systems.
AB  - Emerging multi-electrode-based brain-machine interfaces (BMIs) and large multi
      electrode arrays used in in vitro experiments, enable recording of single
      neuron's activity on multiple electrodes and allow for an in-depth investigation
      of neural preparations, even at a sub-cellular level. However, the use of these
      devices entails stringent area and power consumption constraints for the signal
      processing hardware units. In addition, the high autonomy of these units and an
      ability to automatically adapt to changes in the recorded neural preparations is
      required. Implementing spike detection in close proximity to recording electrodes
      offers the advantage of reducing the transmission data bandwidth. By eliminating
      the need of transmitting the full, redundant recordings of neural activity and by
      transmitting only the spike waveforms or spike times, significant power savings
      can be achieved in the majority of cases. Here, we present a low-complexity,
      unsupervised, adaptable, real-time spike-detection method targeting multi
      electrode recording devices and compare this method to other spike-detection
      methods with regard to complexity and performance. 

PMID- 24110244
TI  - Existence of millisecond-order stable states in time-varying phase
      synchronization measure in EEG signals.
AB  - In this paper, we have developed a new measure of understanding the temporal
      evolution of phase synchronization for EEG signals using cross-electrode
      information. From this measure it is found that there exists a small number of
      well-defined phase-synchronized states, each of which is stable for few
      milliseconds during the execution of a face perception task. We termed these
      quasi-stable states as synchrostates. We used k-means clustering algorithms to
      estimate the optimal number of synchrostates from 100 trials of EEG signals over
      128 channels. Our results show that these synchrostates exist consistently in all
      the different trials. It is also found that from the onset of the stimulus,
      switching between these synchrostates results in well-behaved temporal sequence
      with repeatability which may be indicative of the dynamics of the cognitive
      process underlying that task. Therefore these synchrostates and their temporal
      switching sequences may be used as a new measure of the stability of phase
      synchrony and information exchange between different regions of a human brain. 

PMID- 24110245
TI  - Analysis of intracranial pressure signals recorded during infusion studies using
      the spectral entropy.
AB  - Hydrocephalus includes a range of disorders characterized by clinical symptoms,
      abnormal brain imaging and altered cerebrospinal fluid (CSF) dynamics. Infusion
      tests can be used to study CSF circulation in patients with hydrocephalus. In
      them, intracranial pressure (ICP) is deliberately raised and CSF circulation
      disorders evaluated through measurements of the resulting ICP. In this study, we
      analyzed 77 ICP signals recorded during infusion tests using the spectral entropy
      (SE). Each signal was divided into four artifact-free epochs. The mean SE, <SE>,
      and the standard deviation of SE, SD[SE], were calculated for each epoch.
      Statistically significant differences were found between phases of the infusion
      test using <SE> and SD[SE] (p<1.7 . 10(-3), Bonferroni-corrected Wilcoxon tests).
      Furthermore, we found significantly lower <SE> and SD[SE] values in the plateau
      phase than in the basal phase. These findings suggest that the increase in ICP
      during infusion studies is associated with a significant decrease in irregularity
      and variability of the spectral content of ICP signals, measured in terms of SE.
      We conclude that the spectral analysis of ICP signals could be useful for
      understanding CSF dynamics in hydrocephalus.

PMID- 24110246
TI  - Prediction of nociceptive responses during sedation by time-frequency
      representation.
AB  - The level of sedation in patients undergoing medical procedures evolves
      continuously, such as the effect of the anesthetic and analgesic agents is
      counteracted by pain stimuli. The monitors of depth of anesthesia, based on the
      analysis of the electroencephalogram (EEG), have been progressively introduced
      into the daily practice to provide additional information about the state of the
      patient. However, the quantification of analgesia still remains an open problem.
      The purpose of this work is to analyze the capability of prediction of
      nociceptive responses based on the time-frequency representation (TFR) of EEG
      signal. Functions of spectral entropy, instantaneous power and instantaneous
      frequency were calculated in order to predict the presence or absence of the
      nociceptive responses to different stimuli during sedation in endoscopy
      procedure. Values of prediction probability of Pk above 0.75 and percentages of
      sensitivity and specificity above 70% and 65% respectively were achieved
      combining TFR functions with bispectral index (BIS) and with concentrations of
      propofol (CeProp) and remifentanil (CeRemi). 

PMID- 24110247
TI  - Characterization of noise contaminations in lung sound recordings.
AB  - Lung sound auscultation in non-ideal or busy clinical settings is challenged by
      contaminations of environmental noise. Digital pulmonary measurements are
      inevitably degraded, impeding the physician's work or any further processing of
      the acquired signals. The task is even harder when the patient population
      includes young children. Agitation and/or crying are captured into the
      recordings, additionally to any existing ambient noise. This study focuses on
      characterizing the different types of signal contaminations, expected to be
      encountered during lung sound measurements in non-ideal environments. Different
      noise types were considered, including background talk, radio playing, subject's
      crying, electronic interference sounds and stethoscope displacement artifacts.
      The individual characteristics were extracted, discussed and further compared to
      characteristics of clean segments. Additional exploration of discriminatory
      features led to a spectro-temporal signal representation followed by a standard
      SVM classifier. Although pulmonary and ambient sounds were both dominant in most
      sound clips, such a complex representation was deemed to be adequate, capturing
      most of the signal's distinguishing characteristics. 

PMID- 24110248
TI  - Automatic heart sounds detection and systolic murmur characterization using
      wavelet transform and AR modeling.
AB  - This paper describes a signal processing procedure that identifies the first and
      the second heart sounds (S1 and S2), extracts the systole from the diastole,
      detects and characterizes the systolic murmur found within. The identification of
      heart sounds was facilitated by discrete wavelet transform (DWT) approximation
      using the Coiflet wavelet and followed by using indicators that quantify signal
      activity and strength. The systole was isolated and divided into smaller short
      segments where the signal activity measure and absolute amplitude were computed.
      S1 and S2, and the onset and duration of a systolic murmur were marked. Using the
      indices derived from AR modeling, a systolic murmur can be characterized by its
      timing, duration, pitch, and shape either as crescendo, decrescendo, crescendo
      decrescendo, or plateau. The performance of the proposed procedure was evaluated
      and proved with clinically recorded systolic murmur episodes. 

PMID- 24110249
TI  - Effect of premature activation in analyzing QT dynamics instability using QT-RR
      model for ventricular fibrillation and healthy subjects.
AB  - Perturbations in the normal heart rate are generally represented by the presence
      of premature activation (PA) beats in the surface electrocardiogram (ECG). The
      presence of PA is one of the main reasons of instability in QT dynamics which
      could initiate arrhythmia. Analyzing Boundary-Input Boundary-Output (BIBO)
      stability of the short term linear autoregressive QT-RR model is a way of
      detecting instability in QT dynamics from the ECG. The aim of this paper is to
      investigate if PA is the only reason for instability in the ventricular
      repolarisation process, which is denoted by QT interval of surface ECG. Ten
      healthy subjects with normal sinus rhythm and seven patients with sustained
      ventricular tachycardia (VT) were analyzed in this study. 10 min long ECG data
      were collected from each subject of the healthy group and 10 min ECG before the
      start of VT were taken for each subject of the VT group. Autoregressive QT-RR
      model was derived for each non-overlapping 1 min long ECG segment of the 10 min
      long ECG data. Instability in QT dynamics was quantified by measuring the numbers
      of unstable segments in ECG data for each subject ( ). Results of this study
      revealed that like the VT group subjects, QT instability detected by QT-RR model
      is also found in healthy subjects whose ECG segments are mostly free from PA
      beats. This finding indicates that BIBO unstable QT characteristics might arise
      from other inherent factors of cardiovascular system in addition to PA. 

PMID- 24110250
TI  - Improved ECG pre-processing for beat-to-beat QT interval variability measurement.
AB  - The aim of this study was to enhance the ECG pre-processing modalities for beat
      to-beat QT interval variability measurement based on template matching. The R
      peak detection algorithm has been substituted and an efficient baseline removal
      algorithm has been implemented in existing computer software. To test performance
      we used simulated ECG data with fixed QT intervals featuring Gaussian noise,
      baseline wander and amplitude modulation and two alternative algorithms. We
      computed the standard deviation of beat-to-beat QT intervals as a marker of QT
      interval variability (QTV). Significantly a lower beat-to-beat QTV was found in
      the updated approach compared the original algorithm. In addition, the updated
      template matching computer software outperformed the previous version in
      discarding fewer beats. In conclusion, the updated ECG preprocessing algorithm is
      recommended for more accurate quantification of beat-to-beat QT interval
      variability. 

PMID- 24110251
TI  - Statistical modeling of the atrioventricular node during atrial fibrillation:
      data length and estimator performance.
AB  - The atrioventricular (AV) node plays a central role during atrial fibrillation
      (AF). We have recently proposed a statistical AV node model defined by parameters
      characterizing the arrival rate of atrial impulses, the probability of an impulse
      choosing either one of the dual AV nodal pathways, the refractory periods of the
      pathways, and the prolongation of refractory periods. All model parameters are
      estimated from the RR series using maximum likelihood (ML) estimation, except for
      the mean arrival rate of atrial impulses which is estimated by the AF frequency
      derived from the f-waves. The aim of this study is to present a unified approach
      to ML estimation which also involves the shorter refractory period, thus avoiding
      our previous Poincare plot analysis which becomes biased. In addition, the number
      of RR intervals required for accurate parameter estimation is presented. The
      results show that the shorter refractory period can be accurately estimated, and
      that the resulting estimates converge to the true values when about 500 RR
      intervals are available. 

PMID- 24110252
TI  - Are standard heart rate variability measures associated with the self-perception
      of stress of firefighters in action?
AB  - Stress is a major factor for the degradation of cardiac health in first responder
      professionals such as firefighters. Monitoring stress during real events might be
      the key for controlling this problem. In this paper we inspect how standard heart
      rate variability (HRV) measures are associated with the self-perception of stress
      of firefighters in action, supported by an advanced technological solution to
      acquire this data. Results obtained from more than 94 hours of annotated ECG
      recordings of firefighters in action are promising, showing positive association
      with various standard HRV measures. Given the richness of the gathered data, we
      have also measured the association of the HRV measures with the stage of a
      firefighting event (pre, during, post), obtaining some interesting results that
      hint that the psychological impact of the post-event may be one of the most
      concerning situations for a firefighter, motivating further studies on this in
      the future. 

PMID- 24110253
TI  - Higher order spectral analysis of heart rate variability in pregnancy and
      postpartum.
AB  - This paper presents the study of bispectrum analysis methods of heart rate
      variability in normotensive pregnant and postpartum women. The self and cross
      spectral components are estimated from bispectrum of ECG of pregnant and
      postpartum women. It is observed that, very low frequency (VLF) and low frequency
      (LF) component coupling increases while the high frequency (HF) coupling and
      cross coupling between VLF-LF, VLF-HF and LF-HF decreases throughout the
      pregnancy. The power at very high frequencies decreases as gestation age
      progresses. Significant differences are found in similar and cross coupling
      frequency components in all three trimesters and postpartum. The results indicate
      that one possible discriminating dynamics for the pregnant women in all three
      trimesters is the absence of nonlinear interactions between the sympathetic and
      parasympathetic nervous systems. 

PMID- 24110254
TI  - A nonlinear heartbeat dynamics model approach for personalized emotion
      recognition.
AB  - Emotion recognition based on autonomic nervous system signs is one of the
      ambitious goals of affective computing. It is well-accepted that standard signal
      processing techniques require relative long-time series of multivariate records
      to ensure reliability and robustness of recognition and classification
      algorithms. In this work, we present a novel methodology able to assess
      cardiovascular dynamics during short-time (i.e. < 10 seconds) affective stimuli,
      thus overcoming some of the limitations of current emotion recognition
      approaches. We developed a personalized, fully parametric probabilistic framework
      based on point-process theory where heartbeat events are modelled using a 2(nd)
      order nonlinear autoregressive integrative structure in order to achieve
      effective performances in short-time affective assessment. Experimental results
      show a comprehensive emotional characterization of 4 subjects undergoing a
      passive affective elicitation using a sequence of standardized images gathered
      from the international affective picture system. Each picture was identified by
      the IAPS arousal and valence scores as well as by a self-reported emotional label
      associating a subjective positive or negative emotion. Results show a clear
      classification of two defined levels of arousal, valence and self-emotional state
      using features coming from the instantaneous spectrum and bispectrum of the
      considered RR intervals, reaching up to 90% recognition accuracy. 

PMID- 24110255
TI  - Retinal ganglion cells electrophysiology: the effect of cell morphology on
      impulse waveform.
AB  - There are 16 morphologically defined classes of rats retinal ganglion cells
      (RGCs). Using computer simulation of a realistic anatomically correct A1 mouse
      RGC, we investigate the effect of the cell's morphology on its impulse waveform,
      using the first-, and second-order time derivatives as well as the phase plot
      features. Using whole cell patch clamp recordings, we recorded the impulse
      waveform for each of the rat RGCs types. While we found some clear differences in
      many features of the impulse waveforms for A2 and B2 cells compared to other cell
      classes, many cell types did not show clear differences. 

PMID- 24110256
TI  - Monitoring of peripheral vascular condition using a log-linearized arterial
      viscoelastic index during endoscopic thoracic sympathectomy.
AB  - This paper proposes a novel technique to support the monitoring of peripheral
      vascular conditions using biological signals such as electrocardiograms, arterial
      pressure values and pulse oximetry plethysmographic waveforms. In this approach,
      a second-order log-linearized model (referred to here as a log-linearized
      peripheral arterial viscoelastic model) is used to describe the non-linear
      viscoelastic relationship between blood pressure waveforms and photo
      plethysmographic waveforms. The proposed index enables estimation of peripheral
      arterial wall stiffness changes induced by sympathetic nerve activity. The
      validity of the method is discussed here based on the results of peripheral
      vascular condition monitoring conducted during endoscopic thoracic sympathectomy
      (ETS). The results of ETS monitoring showed significant changes in stiffness
      variations between the periods before and during the procedures observed (p <
      0.01) as well as during and after them (p < 0.01), so that it was confirmed that
      sympathetic nerve activity is drastically decreased in the area around the
      monitoring site after the thoracic sympathetic nerve trunk on the monitoring side
      is successfully blocked. In addition, no change was observed in the values of the
      proposed index during the ETS procedure on the side opposite that of the
      monitoring site. The experimental results obtained clearly show the proposed
      method can be used to assess changes in sympathetic nerve activity during ETS. 

PMID- 24110257
TI  - A log-linearized arterial viscoelastic model for evaluation of the carotid
      artery.
AB  - This paper proposes a method for qualitatively estimating the mechanical
      properties of arterial walls on a beat-to-beat basis through noninvasive
      measurement of continuous arterial pressure and arterial diameter using an
      ultrasonic device. First, in order to describe the nonlinear relationships
      linking arterial pressure waveforms and arterial diameter waveforms as well as
      the viscoelastic characteristics of arteries, we developed a second-order
      nonlinear model (called the log-linearized arterial viscoelastic model) to allow
      estimation of arterial wall viscoelasticity. Next, to verify the validity of the
      proposed method, the viscoelastic indices of the carotid artery were estimated.
      The results showed that the proposed model can be used to accurately approximate
      the mechanical properties of arterial walls. It was therefore deemed suitable for
      qualitative evaluation of arterial viscoelastic properties based on noninvasive
      measurement of arterial pressure and arterial diameter. 

PMID- 24110258
TI  - Wavelet packet analysis of disease-altered recurrence dynamics in the long-term
      spatiotemporal vectorcardiogram (VCG) signals.
AB  - Vectorcardiogram (VCG) signals contain a wealth of dynamic information pertinent
      to space-time cardiac electrical activities. However, few, if any, previous
      investigations have studied disease-altered nonlinear dynamics in the
      spatiotemporal VCG signals. Most previous nonlinear dynamic methods considered
      the time-delay reconstructed state space from a single ECG trace. This paper
      presents a novel multiscale recurrence approach to not only explore VCG
      recurrence dynamics but also resolve the issue of recurrence computation for the
      large-scale datasets. As opposed to the traditional single-scale recurrence
      analysis, we characterize and quantify the recurrence behaviours in multiple
      wavelet scales. In addition, wavelet dyadic subsampling enables the large-scale
      recurrence analysis, but it is used to be highly expensive for a long-term time
      series. The classification experiments show that multiscale recurrence analysis
      detects the myocardial infarctions from 3-lead VCG with an average sensitivity of
      96.8% and specificity of 92.8%, which show superior performance (i.e., 5.6%
      improvements) to the single-scale recurrence analysis. 

PMID- 24110259
TI  - A comparative analysis of alternative approaches for quantifying nonlinear
      dynamics in cardiovascular system.
AB  - Heart rate variability (HRV) analysis has emerged as an important research topic
      to evaluate autonomic cardiac function. However, traditional time and frequency
      domain analysis characterizes and quantify only linear and stationary phenomena.
      In the present investigation, we made a comparative analysis of three alternative
      approaches (i.e., wavelet multifractal analysis, Lyapunov exponents and
      multiscale entropy analysis) for quantifying nonlinear dynamics in heart rate
      time series. Note that these extracted nonlinear features provide information
      about nonlinear scaling behaviors and the complexity of cardiac systems. To
      evaluate the performance, we used 24-hour HRV recordings from 54 healthy subjects
      and 29 heart failure patients, available in PhysioNet. Three nonlinear methods
      are evaluated not only individually but also in combination using three
      classification algorithms, i.e., linear discriminate analysis, quadratic
      discriminate analysis and k-nearest neighbors. Experimental results show that
      three nonlinear methods capture nonlinear dynamics from different perspectives
      and the combined feature set achieves the best performance, i.e., sensitivity
      97.7% and specificity 91.5%. Collectively, nonlinear HRV features are shown to
      have the promise to identify the disorders in autonomic cardiovascular function. 

PMID- 24110260
TI  - Prostate cancer localization by novel magnetic resonance dispersion imaging.
AB  - Diagnosis and focal treatment of prostate cancer, the most prevalent form of
      cancer in men, is hampered by the limits of current clinical imaging.
      Angiogenesis imaging is a promising option for detection and localization of
      prostate cancer. It can be imaged by dynamic contrast-enhanced (DCE) MRI,
      assessing microvascular permeability as an indicator for angiogenesis. However,
      information on microvascular architecture changes associated with angiogenesis is
      not available. This paper presents a new model enabling the combined assessment
      of microvascular permeability and architecture. After the intravenous injection
      of a gadolinium-chelate bolus, time-concentration curves (TCCs) are measured by
      DCE-MRI at each voxel. According to the convective dispersion equation, the
      microvascular architecture is reflected in the dispersion coefficient. A solution
      of this equation is therefore proposed to represent the intravascular blood
      plasma compartment in the Tofts model. Fitting the resulting model to TCCs
      measured at each voxel leads to the simultaneous generation of a dispersion and a
      permeability map. Measurement of an arterial input function is no longer
      required. Preliminary validation was performed by spatial comparison with the
      histological results in seven patients referred for radical prostatectomy. Cancer
      localization by the obtained dispersion maps provided an area under the receiver
      operating characteristic curve equal to 0.91. None of the standard DCE-MRI
      parametric maps could outperform this result, motivating towards an extended
      validation of the method, also aimed at investigating other forms of cancer with
      pronounced angiogenic development. 

PMID- 24110261
TI  - Bone marrow perfusion of proximal femur varied with BMD--a longitudinal study by
      DCE-MRI.
AB  - This study investigated bone marrow perfusion at proximal femur varying with bone
      mineral density (BMD) and aging over 4 years. Dynamic contrast enhanced MRI data
      was extracted pixel-by-pixel and classified into 3 patterns to indicate the
      perfusion function. Eighty-seven elderly females were involved. A notable reduced
      perfusion as a whole was observed in osteoporotic subjects. Moreover, perfusion
      distribution varies as BMD decreases, especially at the area crossing the femoral
      neck to the shaft. Consistent for all subjects, the perfusion decreases
      significantly from the lesser trochanter to the greater trochanter. Further, the
      subjects with good bone marrow perfusion would keep stable BMD after 4 years,
      while for those with bad perfusion, their BMD consistently decreased over 4
      years. The results indicated that the bone marrow perfusion function interacts
      with bone modeling and could have a long term effect on BMD. A good perfusion
      function would help to keep the bone health. 

PMID- 24110262
TI  - Registration of abdominal tumor DCE-MRI data based on deconvolution of joint
      statistics.
AB  - The analysis of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)
      data of body tumors presents several challenges. The accumulation of contrast
      agent in tissues results in a temporally varying contrast in an image series. At
      the same time, the body regions are subject to potentially extensive motion
      mainly due to breathing, heart beat, and peristalsis. This complicates any
      further automated analysis of a DCE-MRI time series such as for tumor lesion
      segmentation and volumetry. To address this problem we propose a novel effective
      non-rigid registration method based on the restoration of the joint statistics of
      pairs of images in the time series. Every image in the time series is registered
      to a reference one from the contrast enhanced phase. The pairwise registration is
      performed with deconvolution of the joint statistics, forcing the results back to
      the spatial domain and regularizing them with Gaussian spatial smoothing. The
      registration method has been validated with both a simulated phantom as well as
      real datasets with improved results for both its accuracy and efficiency. 

PMID- 24110263
TI  - Free induction decay MR signal measurements toward ultra-low field MRI with an
      optically pumped atomic magnetometer.
AB  - Ultra-low field magnetic resonance imaging (ULF-MRI) has attracted attention
      because of its low running costs and minimum patient exposure. An optically
      pumped atomic magnetometer (OPAM) is a magnetic sensor with high sensitivity in
      the low frequency range, which does not require a cryogenic cooling system. In an
      effort to develop a ULF-MRI, we attempted to measure the free induction decay MR
      signals with an OPAM. We successfully detected the MR signals by combining an
      OPAM and a flux transformer, demonstrating the feasibility of the proposed
      system. 

PMID- 24110264
TI  - Accelerating k-t sparse using k-space aliasing for dynamic MRI imaging.
AB  - Dynamic imaging is challenging in MRI and acceleration techniques are usually
      needed to acquire dynamic scene. K-t sparse is an acceleration technique based on
      compressed sensing, it acquires fewer amounts of data in k-t space by pseudo
      random ordering of phase encodes and reconstructs dynamic scene by exploiting
      sparsity of k-t space in transform domain. Another recently introduced technique
      accelerates dynamic MRI scans by acquiring k-space data in aliased form. K-space
      aliasing technique uses multiple RF excitation pulses to deliberately acquire
      aliased k-space data. During reconstruction a simple Fourier transformation along
      time frames can unaliase the acquired aliased data. This paper presents a novel
      method to combine k-t sparse and k-space aliasing to achieve higher acceleration
      than each of the individual technique alone. In this particular combination, a
      very critical factor of compressed sensing, the ratio of the number of acquired
      phase encodes to the number of total phase encode (n/N) increases therefore
      compressed sensing component of reconstruction performs exceptionally well.
      Comparison of k-t sparse and the proposed technique for acceleration factors of
      4, 6 and 8 is demonstrated in simulation on cardiac data. 

PMID- 24110265
TI  - Under-sampling trajectory design for compressed sensing based DCE-MRI.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) needs high
      temporal and spatial resolution to accurately estimate quantitative parameters
      and characterize tumor vasculature. Compressed Sensing (CS) has the potential to
      accomplish this mutual importance. However, the randomness in CS under-sampling
      trajectory designed using the traditional variable density (VD) scheme may
      translate to uncertainty in kinetic parameter estimation when high reduction
      factors are used. Therefore, accurate parameter estimation using VD scheme
      usually needs multiple adjustments on parameters of Probability Density Function
      (PDF), and multiple reconstructions even with fixed PDF, which is inapplicable
      for DCE-MRI. In this paper, an under-sampling trajectory design which is robust
      to the change on PDF parameters and randomness with fixed PDF is studied. The
      strategy is to adaptively segment k-space into low-and high frequency domain, and
      only apply VD scheme in high-frequency domain. Simulation results demonstrate
      high accuracy and robustness comparing to VD design. 

PMID- 24110266
TI  - Comparison of causality analysis on simultaneously measured fMRI and NIRS signals
      during motor tasks.
AB  - Brain activity can be measured using different modalities. Since most of the
      modalities tend to complement each other, it seems promising to measure them
      simultaneously. In to be presented research, the data recorded from Functional
      Magnetic Resonance Imaging (fMRI) and Near Infrared Spectroscopy (NIRS),
      simultaneously, are subjected to causality analysis using time-resolved partial
      directed coherence (tPDC). Time-resolved partial directed coherence uses the
      principle of state space modelling to estimate Multivariate Autoregressive (MVAR)
      coefficients. This method is useful to visualize both frequency and time dynamics
      of causality between the time series. Afterwards, causality results from
      different modalities are compared by estimating the Spearman correlation. In to
      be presented study, we used directionality vectors to analyze correlation, rather
      than actual signal vectors. Results show that causality analysis of the fMRI
      correlates more closely to causality results of oxy-NIRS as compared to deoxy
      NIRS in case of a finger sequencing task. However, in case of simple finger
      tapping, no clear difference between oxy-fMRI and deoxy-fMRI correlation is
      identified. 

PMID- 24110267
TI  - Influences of blood flow changes in cerebrospinal fluid and skin layers on
      optical mapping.
AB  - In optical mapping for imaging brain activity, the effect of blood flow changes
      in superficial tissues such as the cerebrospinal fluid (CSF) and skin layers
      should be considered. However, it is difficult to know those changes in in vivo
      experiments. To investigate the influence of blood flow changes in CSF and skin
      layers on optical mapping, we perform numerical simulations of optical mapping by
      solving the photon diffusion equation for layered-models simulating human heads
      using the finite element method (FEM). The results show that mapping images of
      activated region in the gray matter layer are affected by the existence of blood
      vessels in CSF layer and by the blood flow changes in the skin layer. The
      increases in both the vessel size and vessel absorption coefficient reduce the
      sensitivity of the mapping images to the brain activity in the gray matter. On
      the other hand, the increase in the vessel volume fraction in the skin layer
      increases the sensitivity of the mapping images. 

PMID- 24110268
TI  - Simulating nailfold capillaroscopy sequences to evaluate algorithms for blood
      flow estimation.
AB  - The effects of systemic sclerosis (SSc)--a disease of the connective tissue
      causing blood flow problems that can require amputation of the fingers--can be
      observed indirectly by imaging the capillaries at the nailfold, though taking
      quantitative measures such as blood flow to diagnose the disease and monitor its
      progression is not easy. Optical flow algorithms may be applied, though without
      ground truth (i.e. known blood flow) it is hard to evaluate their accuracy. We
      propose an image model that generates realistic capillaroscopy videos with known
      flow, and use this model to quantify the effect of flow rate, cell density and
      contrast (among others) on estimated flow. This resource will help researchers to
      design systems that are robust under real-world conditions.

PMID- 24110269
TI  - Global optimization of optimal angiographic viewing angles for coronary arteries
      with multiple segments.
AB  - For angiographic images, different imaging angles may lead to different degrees
      of foreshortening and overlap, which hence considerably interferes with the
      angiogram based diagnosis of vascular diseases. In this study, a composite
      optimization method is proposed to determine the optimal viewing angle of
      angiograms, which can fully considerate stenosis and the interference caused due
      to multiple vascular segments. In order to obtain the optimal angle for segments
      at multiple branches' intersection, a hyper plane optimization method is proposed
      to separate the relative branches. The optimal angle for stenosis is designed by
      minimizing area of the projections of the vascular segments. The multiple
      segments and the stenosis optimization are integrated with the foreshortening and
      overlap, which can hence give a more objective viewing angle of the coronary
      arteries from angiographic images. Experimental results demonstrate that the
      proposed method is very effective and robust for optimizing the projection angle.

PMID- 24110270
TI  - Application of fluorescent PSF for 3D reconstruction of absorbing structure using
      slab transillumination images.
AB  - In transillumination imaging of an animal body using near-infrared light, the
      image is blurred due to the strong scattering in the tissue. We have devised the
      depth-dependent point spread function (PSF) to suppress the scattering effect in
      fluorescent imaging. In this study, we applied this principle and developed a
      technique to reconstruct the absorbing structure in turbid medium without using
      fluorescent material. In experiments, the feasibility and effectiveness of the
      proposed technique were verified. 

PMID- 24110271
TI  - Depth estimation and image improvement of fluorescent objects in scattering
      medium with unknown optical parameters.
AB  - The depth of fluorescent source is required to suppress the scattering effect in
      transcutaneous fluorescent imaging. We have developed a technique to estimate the
      depth using two light sources. However, with this technique, the reduced
      scattering coefficient (MUs') and the absorption coefficient (MUa) of the
      scattering medium have to be known a priori. To eliminate this requirement, we
      devised a technique that uses three excitation sources. The feasibility of the
      proposed technique was verified in both computer simulation and experiment. It
      was demonstrated that we could estimate the depth of the fluorescent source and
      improve the fluorescent image even with MUs' and MUa variation. 

PMID- 24110272
TI  - Theory of Dynamic Pulsatile Spectroscopy for photoplethysmographic signals
      analysis.
AB  - Photoplethysmography (PPG) is a technique that uses light to non-invasively
      obtain a volumetric measurement of an organ with each cardiac cycle. Pulse
      Oximetry (PO) is an empirical technique which allows the arterial blood oxygen
      saturation (SpO2) evaluation from the PPG signals. There have been many reports
      in the literature suggesting that other arterial blood chemical components can be
      evaluated from the PPG signals. Most attempts to perform such evaluation on
      empirical bases have failed, especially for components concentrations. This paper
      introduces a non-empirical rational theory called Dynamic Pulsatile Spectroscopy
      (DPS) which can be used to analytically investigate the phenomena of PPG. The DPS
      theory provides the mathematically rigid method of how PPG signals can be used
      for arterial blood analysis to evaluate its chemical component concentrations and
      molar fractions spectroscopically and transcutaneously. It also highlights what
      other signals might be required for such evaluation. DPS opens the possibility of
      extending PPG application for blood analysis beyond conventional PO. The DPS
      basic principles are introduced in this paper. 

PMID- 24110273
TI  - Pilot investigation of anterior fontanelle photoplethysmographic signals and
      their suitability in estimating arterial oxygen saturation.
AB  - There is a need for more reliable, non-invasive and alternative measurement sites
      for the monitoring of arterial blood oxygen saturation in critically ill newborns
      at times of peripheral compromise. A pilot investigation on 14 Intensive Care
      Unit (ICU) newborns was conducted utilizing custom-made reflectance
      photoplethysmographic (PPG) sensors placed at the fontanelle and foot. The
      results suggest that the fontanelle is sensitive to changes in saturation, where
      saturation values obtained from the custom sensor were compared against
      commercial pulse oximeter values and results from a blood gas analyzer, however
      careful placement of the sensor at the fontanelle is an issue that needs further
      investigation. 

PMID- 24110274
TI  - A new method for respiratory-volume monitoring based on long-period fibre
      gratings.
AB  - Respiratory-volume monitoring is an indispensable part of mechanical ventilation.
      Here we present a new method of the respiratory-volume measurement based on a
      single fibre-optical long-period sensor of bending and the correlation between
      torso curvature and lung volume. Unlike the commonly used air-flow based
      measurement methods the proposed sensor is drift-free and immune to air-leaks. In
      the paper, we explain the working principle of sensors, a two-step calibration
      test measurement procedure and present results that establish a linear
      correlation between the change in the local thorax curvature and the change of
      the lung volume. We also discuss the advantages and limitations of these sensors
      with respect to the current standards. 

PMID- 24110275
TI  - Pulse oximetry of body cavities and organs.
AB  - The focus of this paper will be in the development and in vivo applications of
      new custom made photoplethysmographic (PPG) and pulse oximetry optical and fiber
      optic sensors and instrumentation in an effort to investigate their suitability
      in the estimation of blood oxygen saturation and their contribution in the
      assessment of organ/tissue perfusion and viability. The paper describes the
      development of optical and fiber optic PPG and blood oxygen saturation (SpO2)
      sensors and covers examples of application areas including real-time PPG
      monitoring from body cavities (esophagus) and solid or hollow organs (bowel,
      liver, stomach, brain, etc). The clinical studies presented successfully
      demonstrated the feasibility in acquiring PPGs and estimating blood oxygen
      saturation values from a variety of organs and tissues. The technological
      developments and the measurements presented in this work pave the way in a new
      era of pulse oximetry where direct and continuous monitoring of blood oxygen
      saturation of internal organs and tissues could be made possible. 

PMID- 24110276
TI  - Towards on-chip integration of brain imaging photodetectors using standard CMOS
      process.
AB  - The main effects of on-chip integration on the performance and efficiency of
      silicon avalanche photodiode (SiAPD) and photodetector front-end is addressed in
      this paper based on the simulation and fabrication experiments. Two different
      silicon APDs are fabricated separately and also integrated with a transimpedance
      amplifier (TIA) front-end using standard CMOS technology. SiAPDs are designed in
      p+/n-well structure with guard rings realized in different shapes. The TIA front
      end has been designed using distributed-gain concept combined with resistive
      feedback and common-gate topology to reach low-noise and high gain-bandwidth
      product (GBW) characteristics. The integrated SiAPDs show higher signal-to-noise
      ratio (SNR), sensitivity and detection efficiency comparing to the separate
      SiAPDs. The integration does not show a significant effect on the gain and
      preserves the low power consumption. Using APDs with p-well guard-ring is
      preferred due to the higher observed efficiency after integration. 

PMID- 24110277
TI  - Camera-based system for contactless monitoring of respiration.
AB  - Reliable, remote measurement of respiration rate is still an unmet need in
      clinical and home settings. Although the predictive power of respiratory rate for
      a patient's health status is well-known, this vital sign is often measured
      inaccurately or not at all. In this paper we propose a camera-based monitoring
      system to reliably measure respiration rate without any body contact. A
      computationally efficient algorithm to extract raw breathing signals from the
      video stream has been developed and implemented. Additionally, a camera offers an
      easy access to motion information in the analyzed scenes, which significantly
      improves subsequent breath-to-breath classification. The performance of the
      sensor system was evaluated using data acquired with healthy volunteers, as well
      as with a mechanical phantom, under laboratory conditions covering a large range
      of challenging measurement situations. 

PMID- 24110278
TI  - A meshless Local Boundary Integral Equation (LBIE) method for cell proliferation
      predictions in bone healing.
AB  - Bone healing involves a series of complicated cellular and molecular mechanisms
      that result in bone formation. Several mechanobiological models have been
      developed to simulate these cellular mechanisms via diffusive processes. In most
      cases solution to diffusion equations is accomplished using the Finite Element
      Method (FEM) which however requires global remeshing in problems with moving or
      new born surfaces or material phases. This limitation is addressed in meshless
      methods in which no background cells are needed for the numerical solution of the
      integrals. In this study a new meshless Local Boundary Integral Equation (LBIE)
      method is employed for deriving predictions of cell proliferation during bone
      healing. First a benchmark problem is presented to assess the accuracy of the
      method. Then the LBIE method is utilized for the solution of cell diffusion
      problem in a two-dimensional (2D) model of fractured model. Our findings indicate
      that the proposed here LBIE method can successfully predict cell distributions
      during fracture healing. 

PMID- 24110280
TI  - GPU technology as a platform for accelerating local complexity analysis of
      protein sequences.
AB  - The use of GPGPU programming paradigm (running CUDA-enabled algorithms on GPU
      cards) in Bioinformatics showed promising results [1]. As such a similar approach
      can be used to speedup other algorithms such as CAST, a popular tool used for
      masking low-complexity regions (LCRs) in protein sequences [2] with increased
      sensitivity. We developed and implemented a CUDA-enabled version (GPU_CAST) of
      the multi-threaded version of CAST software first presented in [3] and optimized
      in [4]. The proposed software implementation uses the nVIDIA CUDA libraries and
      the GPGPU programming paradigm to take advantage of the inherent parallel
      characteristics of the CAST algorithm to execute the calculations on the GPU card
      of the host computer system. The GPU-based implementation presented in this work,
      is compared against the multi-threaded, multi-core optimized version of CAST [4]
      and yielded speedups of 5x-10x for large protein sequence datasets. 

PMID- 24110281
TI  - A comparison of multi-label techniques based on problem transformation for
      protein functional prediction.
AB  - A comparative analysis of four multi-label classification methods is performed in
      order to determine the best topology for the problem of protein function
      prediction, using support vector machines as base classifiers. Comparisons are
      done in terms of performance and computational cost of parallelized versions of
      the algorithms, for determining its applicability in high-throughput scenarios.
      Results show that the performance of the binary relevance strategy, together with
      a technique of class balance, remains above several recently proposed techniques
      for the problem at hand, while employing the smallest computational cost when
      parallelized. However, stacked classfiers and chain classifications can be
      conveniently used in pipelines, due to the low number of false positives
      reported.

PMID- 24110282
TI  - Fast and robust extraction of reliable protein signal profiles from mass
      spectrometry data by introducing the concept of Single Channel ICA with
      statistical offset correction.
AB  - In this paper, we introduce the concept of Single Channel Independent Component
      Analysis (SCICA) for fast extraction of protein profiles from the mass spectra
      data. Subsequently we propose one offset-correction scheme on the basis of the
      statistical data analysis of the SCICA-based estimated protein profiles to ensure
      robustness of the proposed algorithm. The proposed method is also validated
      rigorously against the simulated data. Such concept, to the best of our knowledge
      is proposed for the first time in this context of protein profiling and we
      envisage that the proposed concept will find potential applications in bio-marker
      discovery especially for cancers. 

PMID- 24110283
TI  - An optimized and low-cost FPGA-based DNA sequence alignment--a step towards
      personal genomics.
AB  - DNA sequence alignment is a cardinal process in computational biology but also is
      much expensive computationally when performing through traditional computational
      platforms like CPU. Of many off the shelf platforms explored for speeding up the
      computation process, FPGA stands as the best candidate due to its performance per
      dollar spent and performance per watt. These two advantages make FPGA as the most
      appropriate choice for realizing the aim of personal genomics. The previous
      implementation of DNA sequence alignment did not take into consideration the
      price of the device on which optimization was performed. This paper presents
      optimization over previous FPGA implementation that increases the overall speed
      up achieved as well as the price incurred by the platform that was optimized. The
      optimizations are (1) The array of processing elements is made to run on change
      in input value and not on clock, so eliminating the need for tight clock
      synchronization, (2) the implementation is unrestrained by the size of the
      sequences to be aligned, (3) the waiting time required for the sequences to load
      to FPGA is reduced to the minimum possible and (4) an efficient method is devised
      to store the output matrix that make possible to save the diagonal elements to be
      used in next pass, in parallel with the computation of output matrix. Implemented
      on Spartan3 FPGA, this implementation achieved 20 times performance improvement
      in terms of CUPS over GPP implementation. 

PMID- 24110284
TI  - Differential network biology reveals a positive correlation between a novel
      protein-protein interaction and cancer cells migration.
AB  - This paper introduces a differential network biology for discovering tumor
      migration. We applied statistical methods to prioritize PPI candidates and an in
      situ proximity ligation assay to verify 67 endogenous PPIs among 21 interlinked
      pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory
      cells) and Mahlavu (highly migratory cells). Differential network biology
      analysis was applied to determine the novel interaction, CRKL-FLT1, has a high
      centrality ranking, and the expression of this interaction is strongly correlated
      with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL
      and FLT1 in HCC cells leads to a decrease in cell migration. This study
      demonstrated that functional exploration of a disease network with differential
      network in interlinked pathways via PPIs can be used to discover tumor migration.

PMID- 24110285
TI  - Information decoding in microscopic biological processes.
AB  - The cellular and intracellular dynamics are intrinsically stochastic and dynamic.
      However, whole biological system such as a cell or our body can function very
      robustly and stably even though they are composed of these stochastic reactions.
      To account for this riddling relation between macroscopic robustness and
      microscopic stochasticity, I propose a mechanism that information relevant for
      stable and reliable operation of a biological system is embedded in apparently
      stochastic and noisy behavior of their components. To show validity of this
      possibility, I demonstrates that information can actually be decoded from
      apparently noisy signal when it is processed by an appropriate dynamics derived
      by Bayes' rule. Next, I investigate biological relevance of this possibility by
      showing that several intracellular networks can implement this decoding dynamics.
      Finally, by focusing its dynamical properties, I show the mechanism how the
      derived dynamics can separate information and noise. 

PMID- 24110286
TI  - The dynamics of cellular energetics during continuous yeast culture.
AB  - A plethora of data is accumulating from high throughput methods on metabolites,
      coenzymes, proteins, and nucleic acids and their interactions as well as the
      signalling and regulatory functions and pathways of the cellular network. The
      frozen moment viewed in a single discrete time sample requires frequent
      repetition and updating before any appreciation of the dynamics of component
      interaction becomes possible. Even then in a sample derived from a cell
      population, time-averaging of processes and events that occur in out-of-phase
      individuals blur the detailed complexity of single cell organization.
      Continuously-grown cultures of yeast can become spontaneously self-synchronized,
      thereby enabling resolution of far more detailed temporal structure. Continuous
      on-line monitoring by rapidly responding sensors (O2 electrode and membrane-inlet
      mass spectrometry for O2, CO2 and H2S; direct fluorimetry for NAD(P)H and
      flavins) gives dynamic information from time-scales of minutes to hours.
      Supplemented with capillary electophoresis and gas chromatography mass
      spectrometry and transcriptomics the predominantly oscillatory behaviour of
      network components becomes evident, with a 40 min cycle between a phase of
      increased respiration (oxidative phase) and decreased respiration (reductive
      phase). Highly pervasive, this ultradian clock provides a coordinating function
      that links mitochondrial energetics and redox balance to transcriptional
      regulation, mitochondrial structure and organelle remodelling, DNA duplication
      and cell division events. Ultimately, this leads to a global partitioning of
      anabolism and catabolism and the enzymes involved, mediated by a relatively
      simple ATP feedback loop on chromatin architecture. 

PMID- 24110287
TI  - Robustness of force and stress inference in an epithelial tissue.
AB  - During morphogenesis, the shape of a tissue emerges from collective cellular
      behaviors, which are in part regulated by mechanical and biochemical interactions
      between cells. Quantification of force and stress is therefore necessary to
      analyze the mechanisms controlling tissue morphogenesis. Recently, a mechanical
      measurement method based on force inference from cell shapes and connectivity has
      been developed. It is non-invasive, and can provide space-time maps of force and
      stress within an epithelial tissue, up to prefactors. We previously performed a
      comparative study of three force-inference methods, which differ in their
      approach of treating indefiniteness in an inverse problem between cell shapes and
      forces. In the present study, to further validate and compare the three force
      inference methods, we tested their robustness by measuring temporal fluctuation
      of estimated forces. Quantitative data of cell-level dynamics in a developing
      tissue suggests that variation of forces and stress will remain small within a
      short period of time (~minutes). Here, we showed that cell-junction tensions and
      global stress inferred by the Bayesian force inference method varied less with
      time than those inferred by the method that estimates only tension. In contrast,
      the amplitude of temporal fluctuations of estimated cell pressures differs less
      between different methods. Altogether, the present study strengthens the validity
      and robustness of the Bayesian force-inference method.

PMID- 24110288
TI  - In vivo oriented modeling with consideration of intracellular crowding.
AB  - In vivo reaction space is constrained by complex structures which are made of
      entwined cytoskeletons and organelles; this create the difference between in vivo
      and in vitro in respect of molecular mobility, and it may affect reaction
      processes. Our motivation is to reveal the background mechanisms of the
      properties of molecular behaviors in vivo by numerical approach. For this object,
      we reassembled a pseudo-intracellular environment in 3D lattice space, and
      executed Monte Carlo simulation. By changing the relative amount of non-reactive
      obstacles in the simulation space, we tested the effect of the level of
      crowdedness to the molecular mobility and reaction processes. Our results showed
      that molecules demonstrated anomalous diffusion correlating to the restriction
      level of the reaction space. Reaction processes also showed distinct
      characteristics, that is increase of reaction rate at the beginning of reactions,
      with the decrease of the reaction rate at later time frame of reactions. Our
      results suggested that the anomalous behaviors at singe molecule level in vivo
      could bring an essential difference to the reaction processes and the results. 

PMID- 24110289
TI  - The helical flow total artificial heart: implantation in goats.
AB  - To realize a total artificial heart (TAH) with high performance, high durability,
      good anatomical fitting, and good blood compatibility, the helical flow TAH
      (HFTAH) has been developed with two helical flow pumps having hydrodynamic
      levitation impeller. The HFTAH was implanted in goats to investigate its
      anatomical fitting, blood compatibility, mechanical stability, control stability,
      and so on. The size of the HFTAH was designed to be 80 mm in diameter and 84 mm
      wide. The maximum output was 19 L/min against 100 mmHg of pressure head. Eight
      adult female goats weighting from 45 to 56.3 kg (average 49.7 kg) were used.
      Under the extracorporeal circulation, natural heart was removed at the
      atrioventricular groove and the HFTAH was implanted. The HFTAH was driven with a
      pulsatile mode. The 1/R control was applied when the right atrial pressure
      recovered. The HFTAH could be implanted with good anatomical fitting in all
      goats. Two goats survived for more than a week. One goat is ongoing. Other goats
      did not survive for more than two days with various reasons. In the goats that
      survived for more than a week, the hydrodynamic bearing was worn and broken,
      which indicated that the bearing touched to the shaft. The cause was supposed to
      be the influence of the sucking effect. The potential of the HFTAH could be
      demonstrated with this study. The stability of the hydrodynamic bearing in a
      living body, especially the influence of the sucking effect, was considered to be
      very important and a further study should be necessary. 

PMID- 24110290
TI  - Pulsatile driving of the helical flow pump.
AB  - The helical flow pump (HFP) is newly developed blood pomp for total artificial
      heart (TAH). HFP can work with lower rotational speed than axial and centrifugal
      blood pump. It can be seen reasonable feature to generate pulsatile flow because
      high response performance can be realized. In this article, pulsatility of HFP
      was evaluated using mock circulation loop. Pulsatile flow was generated by
      modulating the rotational speed in various amplitude and heart rate. In the
      experiment, relationship between Pump flow, pump head, rotational speed
      amplitude, heart rate and power consumption is evaluated. As the result, complete
      pulsatile flow with mean flow rate of 5 L/min and mean pressure head of 100 mmHg
      can be obtained at +/- 500 rpm with mean rotational speed of 1378 to 1398 rpm in
      hart rate from 60 to 120. Flow profiles which are non-pulsatile, quasi-pulsatile
      or complete flow can be adjusted arbitrarily. Therefore, HFP has excellent
      pulsatility and control flexibility of flow profile.

PMID- 24110291
TI  - Development of a portable bridge-to-decision blood pump.
AB  - We are developing an axial-flow pump with a cylindrical-impeller without
      airfoils. In the mock experiments of HA02 model a pressure of 13.3 kPa was
      obtained at a rotational speed of 12500 rpm and flow of 5L/min. The obtained
      pressure with HA02 was almost double than an airfoil-type impeller. The 2D
      analysis of hydrodynamic bearings for the pump revealed that a section with 3 or
      more arcs is stable with respect to angular position, and a minimum bearing gap
      of 100 um can be attained at a design bearing gap of 150 um and at a groove depth
      of 100 um.

PMID- 24110292
TI  - Fluid dynamic design for low hemolysis in a hydrodynamically levitated
      centrifugal blood pump.
AB  - We have developed a hydrodynamically levitated centrifugal blood pump for
      extracorporeal circulatory support as a bridge to decision pump. The impeller is
      levitated using hydrodynamic bearings without any complicated control circuit or
      displacement sensor. However, the effect of the outer circumferential velocity
      and the bearing area on the hemolytic property has not been clarified, even if
      the bearing gap is same size. The purpose of this study is to experimentally
      evaluate the effect of the outer circumferential velocity and the bearing area in
      the bearing gaps on the hemolytic property in a hydrodynamically levitated
      centrifugal blood pump. We prepared three models for testing. These models have
      the same bearing gap size by adjusting the impeller levitation position. However,
      the outer circumferential velocity of the impeller and the bearing area in the
      minimum bearing gaps are different. The outer circumferential velocity of the
      impeller and the bearing area were assumed to be related to the maximum shear
      rate and the exposure time. For the evaluation, we conducted an impeller
      levitation performance test and an in vitro hemolysis test. As a result, the
      normalized index of hemolysis (NIH) was reduced from 0.084 g/100 L to 0.040 g/100
      L corresponding to a reduction in the outer circumferential velocity and a
      reduction in the bearing area, even if the minimum bearing gaps were same size.
      We confirmed that, even if the bearing gap was same size under the stably
      levitated condition, the outer circumferential velocity and the bearing area
      should be decreased in order to improve the hemolytic property.

PMID- 24110293
TI  - Effect of impeller flow path on pump performance and impeller stability of the
      monopivot circulatory pump.
AB  - The effect of a cutout on the pump pressure-flow characteristics and the impeller
      stability was quantified using computational fluid dynamics analysis in order to
      provide good hemocompatibility of the monopivot extracorporeal circulation pump.
      As a result, the following findings were clarified. The pump pressure is lower in
      the cutout model than in the no-cutout model. The impeller stability with respect
      to the buoyancy of the impeller is better in the cutout model than in the no
      cutout model. The impeller stability with respect to the impeller tilt is better
      in the cutout model than in the no-cutout model. Therefore, the cutout model, in
      which the geometry corresponds to the commercialized pump, was likely to be
      better than the no-cutout model because the stability that has the possibility to
      decrease the gap instantaneously to increase hemolysis despite the impeller
      rotational speed slightly. 

PMID- 24110294
TI  - Controlling methods of a newly developed extra aortic counter-pulsation device
      using shape memory alloy fibers.
AB  - Diastolic counter-pulsation has been used to provide circulatory augmentation for
      short term cardiac support. The success of intra-aortic balloon pump (IABP)
      therapy has generated interest in long term counter-pulsation strategies to treat
      heart failure patients. The authors have been developing a totally implantable
      extra aortic pulsation device for the circulatory support of heart failure
      patients, using 150 um Ni-Ti anisotropic shape memory alloy (SMA) fibers. These
      fibers contract by Joule heating with an electric current supply. The special
      features of our design are as follow: non blood contacting, extra aortic
      pulsation function synchronizing with the native heart, a wrapping mechanical
      structure for the aorta in order to achieve its assistance as the aortomyoplsty
      and the extra aortic balloon pump. The device consisted of rubber silicone wall
      plates, serially connected for radial contraction. We examined the contractile
      function of the device, as well as it controlling methods; the phase delay
      parameter and the pulse width modulation, in a systemic mock circulatory system,
      with a pneumatically driven silicone left ventricle model, arterial rubber
      tubing, a peripheral resistance unit, and a venous reservoir. The device was
      secured around the aortic tubing with a counter-pulsation mode of 1:4 against the
      heartbeat. Pressure and flow waveforms were measured at the aortic outflow, as
      well as its driving condition of the contraction phase width and the phase delay.
      The device achieved its variable phase control for co-pulsation or counter
      pulsation modes by changing the phase delay of the SMA fibers. Peak diastolic
      pressure significantly augmented, mean flow increased (p<0.05) according to the
      pulse width modulation. Therefore the newly developed extra aortic counter
      pulsation device using SMA fibers, through it controlling methods indicated its
      promising alternative extra aortic approach for non-blood contacting
      cardiovascular circulatory support.

PMID- 24110295
TI  - A new architecture for neural signal amplification in implantable brain machine
      interfaces.
AB  - This paper reports a new architecture for variable gain-bandwidth amplification
      of neural signals to be used in implantable multi-channel recording systems. The
      two most critical requirements in such a front-end circuit are low power
      consumption and chip area, especially as number of channels increases. The
      presented architecture employs a single super-performing amplifier, with tunable
      gain and bandwidth, combined with several low-key preamplifiers and multiplexors
      for multi-channel recordings. This is in contrast to using copies of high
      performing amplifier for each channel as is typically reported in earlier
      literature. The resulting circuits consume lower power and require smaller area
      as compared to existing designs. Designed in 0.5 umCMOS, the 8-channel prototype
      can simultaneously record Local Field Potentials and neural spikes, with an
      effective power consumption of 3.5 uW per channel and net core area of 0.407
      mm(2).

PMID- 24110296
TI  - Development of a very large array for retinal stimulation.
AB  - Retina degeneration is one of the leading causes of blindness nowadays and cannot
      be cured in most cases. It has been shown that electrical stimulation of retinal
      ganglion cells can generate visual perceptions and therefore implantable
      electrode arrays can be possible treatment for these patients. Most implants
      developed for that purpose use electrode arrays with a size of a few millimeters
      squared and therefore could restore only a very small field of vision and hardly
      improve orientation in an unknown environment. In this paper we present results
      of the development of an implantable electrode array covering about 100 mm(2) of
      retinal tissue. 

PMID- 24110297
TI  - A multi-electrode array coupled with fiberoptic for deep-brain optical
      neuromodulation and electrical recording.
AB  - In this paper we developed an integrated device comprised of a multi-electrode
      array coupled with optical fiber for deep-brain optical stimulation and
      electrical recording. We characterized the array device both electrically and
      optically, and conducted in vivo experiments on free moving rats for validation.
      This design of array device provides a viable tool for neuromodulation and neural
      signal acquisition in optogenetics and in other fields of neuroscience studies
      perspectively. 

PMID- 24110298
TI  - WIMAGINE((r)): 64-channel ECoG recording implant for human applications.
AB  - A wireless 64-channel ElectroCorticoGram (ECoG) recording implant named
      WIMAGINE((r)) has been designed for clinical applications. This active
      implantable medical device is able to record ECoG on 64 electrodes with
      selectable gain and sampling frequency, with less than 0.7 uVRMS input referred
      noise in the [0.5 Hz - 300 Hz] band. It is powered remotely through an inductive
      link at 13.56 MHz, communicates wirelessly on the MICS band at 402-405 MHz with a
      custom designed base station connected to a PC and complies with the regulations
      applicable to class III AIMD. The design of the housing and the antenna have been
      optimized to ease the surgery and to take into account all the requirements of a
      clinical trial in particular patient safety and comfort. The main features of
      this WIMAGINE((r)) implantable device and its architecture will be presented, as
      well as its performances and in vivo validations.

PMID- 24110299
TI  - Current steering for high resolution retinal implants.
AB  - To significantly increase the resolution achievable by a retinal prosthesis
      without requiring additional electrodes, a current steering technique could be
      utilized. In this study, a finite element model was constructed to analyze the
      local concentrations of charge carrying ions within a saline bath due to
      concurrent stimulation from two electrodes surrounded by a hexagonal arrangement
      of return electrodes. By altering the return pathways, tissue activation and
      identification of unique stimulation patterns is possible. Ag/Ag-Cl electrodes
      and a voltage controlled current source were developed to validate the finite
      element model, with the model accurately predicting saline bath measurements. The
      average error in the returned currents between the finite element model and
      experimental results was 2% relative to the stimulus current. 

PMID- 24110300
TI  - A 13uW 87dB dynamic range implantable DeltaSigma modulator for full-spectrum
      neural recording.
AB  - Experiment analysis on in-vivo data sequences suggests a wide system dynamic
      range (DR) is required to simultaneously record local field potentials (LFPs),
      extra-cellular spikes, and artifacts/interferences. In this paper, we present a
      13 uW 87 dB DR DeltaSigma modulator for full-spectrum neural recording. To
      achieve a wide DR and low power consumption, a fully-differential topology is
      used with multi-bit (MB) quantization scheme and switched-opamp (SO) technique.
      By adopting a novel fully-clocked scheme, a power-efficient current-mirror SO is
      developed with 50% power saving, which doubles the figure-of-merit (FOM) over its
      counterpart. A new static power-less multi-bit quantizer with 96% power and 69%
      area reduction is also introduced. Besides, instead of metal-insulator-metal
      (MIM) capacitor, three high-density MOS capacitor (MOSCAP) structures are
      employed to reduce circuit area. Measurement results show a peak signal-to-noise
      and distortion ratio (SNDR) of 85 dB with 10 kHz bandwidth at 1.0 V supply,
      corresponding to an FOM of 45 fJ/conv.-step. which is implemented in a 0.18 um
      CMOS. 

PMID- 24110301
TI  - Likelihood Gradient Ascent (LGA): a closed-loop decoder adaptation algorithm for
      brain-machine interfaces.
AB  - Closed-loop decoder adaptation (CLDA) is an emerging paradigm for improving or
      maintaining the online performance of brain-machine interfaces (BMIs). Here, we
      present Likelihood Gradient Ascent (LGA), a novel CLDA algorithm for a Kalman
      filter (KF) decoder that uses stochastic, gradient-based corrections to update KF
      parameters during closed-loop BMI operation. LGA's gradient-based paradigm
      presents a variety of potential advantages over other "batch" CLDA methods,
      including the ability to update decoder parameters on any time-scale, even on
      every decoder iteration. Using a closed-loop BMI simulator, we compare the LGA
      algorithm to the Adaptive Kalman Filter (AKF), a partially gradient-based CLDA
      algorithm that has been previously tested in non-human primate experiments. In
      contrast to the AKF's separate mean-squared error objective functions, LGA's
      update rules are derived directly from a single log likelihood objective, making
      it one step towards a potentially optimal continuously adaptive CLDA algorithm
      for BMIs. 

PMID- 24110302
TI  - Mechanical vibrotactile stimulation effect in motor imagery based brain-computer
      interface.
AB  - Sensory stimulation played a critical role in both motivating subject's
      anticipation in brain-computer interface but also enhancing the sensory-motor
      interaction and closing the sensory motor loop. In this paper, mechanical
      vibrotactile stimulation effect in motor imagery was evaluated on 10 healthy
      subjects, and preliminary results showed that 5 subjects would achieve a reliable
      control above 80% with sensory stimulation as comparable with motor imagery
      without any stimulation. Besides, 3 subjects reached a better control with
      approximately 70% as compared with a chance level of 50% in motor imagery without
      sensory stimulation. Further analysis showed subject who was poor in conventional
      motor imagery condition exhibited enhanced R(2) value distribution in motor
      imagery with sensory stimulation condition. Meanwhile there was sensorimotor
      rhythmic enhancement both at upper alpha band and upper beta band in some
      subjects. But these rhythmic changes resulted performance reduction as
      incongruence of training and testing sets effect from off-line analysis. This
      research provided some guidance in integration of the sensory stimulation channel
      with motor imagery based BCI system. 

PMID- 24110303
TI  - Hierarchical Codebook Visually Evoked Potentials for fast and flexible BCIs.
AB  - Brain-Computer Interfaces provide a direct communication channel from the brain
      to a technical device. One major problem in state-of-the-art BCIs is their low
      communication speed. BCIs based on Codebook Visually Evoked Potentials (cVEP)
      outperform all other non-invasive approaches in terms of information transfer
      rate. Used only in spelling tasks so far, more flexibility with respect to
      stimulus structure and properties is needed. We propose using hierarchical
      codebook vectors together with varying color schemes to increase the stimulus
      flexibility. An off-line study showed that our novel hcVEP approach is capable of
      discriminating groups of targets after only 250 ms of stimulus flickering and the
      final target within the group after 1s. The accuracies are 81% and 67%,
      respectively. Different color schemes (black/white and green/red) are equally
      effective.

PMID- 24110304
TI  - Optimizing low-frequency common spatial pattern features for multi-class
      classification of hand movement directions.
AB  - Recent studies have demonstrated that hand movement directions can be decoded
      from low-frequency electroencephalographic (EEG) signals. This paper proposes a
      novel framework that can optimally select dyadic filter bank common spatial
      pattern (CSP) features in low-frequency band (0-8 Hz) for multi-class
      classification of four orthogonal hand movement directions. The proposed
      framework encompasses EEG signal enhancement, dyadic filter bank CSP feature
      extraction, fuzzy mutual information (FMI)-based feature selection, and one
      versus-rest Fisher's linear discriminant analysis. Experimental results on data
      collected from seven human subjects show that (1) signal enhancement can boost
      accuracy by at least 4%; (2) low-frequency band (0-8 Hz) can adequately and
      effectively discriminate hand movement directions; and (3) dyadic filter bank CSP
      feature extraction and FMI-based feature selection are indispensable for
      analyzing hand movement directions, increasing accuracy by 6.06%, from 60.02% to
      66.08%. 

PMID- 24110305
TI  - Phase synchrony in subject-specific reactive band of EEG for classification of
      motor imagery tasks.
AB  - Recent works on brain functional analysis have highlighted the importance of
      distributed functional networks and synchronized activity between networks in
      mediating cognitive functions. The network perspective is fundamental to relate
      mechanisms of brain functions and the basis for classifying brain states. This
      work analyzes the network mechanisms related to motor imagery tasks based on
      synchronization measure (PLV (phase-locking value)) in EEG alpha-band for the BCI
      Competition IV Data Set. Based on network dissimilarities between motor imagery
      and rest tasks, important nodes and important channel pairs corresponding to
      tasks for all subjects are identified. The identified important channel pairs
      corresponding to tasks demonstrate significant PLV variation in line with the
      experiment protocol. With the selection of subject-specific reactive band, these
      channel pairs provide even more higher variation corresponding to tasks. This
      paper demonstrates the potential of these identified channel pairs in task
      classification for future BCI applications. 

PMID- 24110306
TI  - Semantic-based sound retrieval by ERP in rapid serial auditory presentation
      paradigm.
AB  - "Semantic gap" is the major bottleneck of semantic-based multimedia retrieval
      technique in the field of information retrieval. Studies have shown that robust
      semantic-based image retrieval can be achieved by single-trial visual evoked
      event related potential (ERP) detection. However, the question remains whether
      auditory evoked ERP can be utilized to achieve semantic-based sound retrieval. In
      this paper, we investigated this question in the rapid serial auditory
      presentation (RSAP) paradigm. Eight BCI-naive participants were instructed to
      perform target detection in RSAP sequences with the vocalizations of 8 familiar
      animals as sound stimuli, and we compared ERP components and single-trial ERP
      classification performance between two conditions, the target was a predefined
      specific one, and the targets were different but belonged to the same semantic
      category (i.e., semantic-based sound retrieval). Although the amplitudes of ERP
      components (e.g., N2 and P3) and classification performance decreased a little
      due to the difficulty of the semantic-based sound retrieval tasks, the best two
      participants still achieved the area under the receive operating characteristic
      curve (AUC) of single-trial ERP detection more than 0.77. It suggested that
      semantic-based sound retrieval by auditory evoked ERP was potentially feasible. 

PMID- 24110307
TI  - Bayesian inference in auditory scenes.
AB  - The cocktail party problem is a multi-faceted challenge which encompasses various
      aspects of auditory perception. Its processes underlie the brain's ability to
      detect, identify and classify sound objects; to robustly represent and maintain
      speech intelligibility amidst severe distortions; and to guide actions and
      behaviors in line with complex goals and shifting acoustic soundscapes. Here, we
      present a perspective that considers the powerful Bayesian inference as a
      unifying framework to integrate the role of sensory cues as well as stimulus
      driven priors and top-down schemas including attention. 

PMID- 24110308
TI  - Multipolar current focusing increases spectral resolution in cochlear implants.
AB  - Cochlear implants are highly successful neural prostheses that restore hearing in
      the deaf, often resulting in high levels of speech understanding in quiet
      listening conditions. In more challenging conditions, however, cochlear implant
      subjects often score much lower than their normal-hearing peers, possibly
      reflecting limits of the electrode-neural interface. In this study, we compare
      monopolar stimulation versus focused stimulation, using multipolar channels, to
      test if current focusing can increase spectral resolution. Psychophysical results
      show that current focusing significantly improves subjects' ability to
      discriminate spectral features and detect dynamic modulations in sound stimuli.
      These results suggest that focused stimulation can successfully increase the
      number of effective channels with a cochlear implant and may lead to improved
      hearing in noisy conditions. 

PMID- 24110309
TI  - The effects of attention and visual input on the representation of natural speech
      in EEG.
AB  - Traditionally, the use of electroencephalography (EEG) to study the neural
      processing of natural stimuli in humans has been hampered by the need to
      repeatedly present discrete stimuli. Progress has been made recently by the
      realization that cortical population activity tracks the amplitude envelope of
      speech stimuli. This has led to studies using linear regression methods which
      allow the presentation of continuous speech. One such method, known as stimulus
      reconstruction, has so far only been utilized in multi-electrode cortical surface
      recordings and magnetoencephalography (MEG). Here, in two studies, we show that
      such an approach is also possible with EEG, despite the poorer signal-to-noise
      ratio of the data. In the first study, we show that it is possible to decode
      attention in a naturalistic cocktail party scenario on a single trial (~60 s)
      basis. In the second, we show that the representation of the envelope of auditory
      speech in the cortex is more robust when accompanied by visual speech. The
      sensitivity of this inexpensive, widely-accessible technology for the online
      monitoring of natural stimuli has implications for the design of future studies
      of the cocktail party problem and for the implementation of EEG-based brain
      computer interfaces. 

PMID- 24110310
TI  - The role of augmentative visual training in auditory human-machine-interface
      performance.
AB  - The purpose of this study was to evaluate the effect of augmentative visual
      feedback training on performance using auditory feedback alone for human-machine
      interface (HMI) control. Sixteen healthy participants used bilateral facial
      surface electromyography to achieve two-dimensional control to reach vowel
      targets. Eight participants trained with combined visual and auditory feedback,
      while eight participants trained with real-time auditory feedback only. Each
      subject participated in four sessions over three days; three sessions with their
      designated feedback modality (auditory only or auditory with supplementary
      visual) and a fourth session on the third day using novel vowel targets to test
      generalization of auditory-motor learning. Analyses of variance performed on the
      percentage of total targets reached demonstrated a main effect of group and the
      interaction of group and session. Individuals provided with augmentative visual
      feedback during training outperformed individuals using auditory feedback alone
      in initial training sessions. However, training with augmentative visual feedback
      had no effect on individuals' training and generalization performance using
      auditory feedback alone after three days of training. 

PMID- 24110311
TI  - Towards a next-generation hearing aid through brain state classification and
      modeling.
AB  - Traditional brain-state classifications are primarily based on two well-known
      neural biomarkers: P300 and motor imagery / event-related frequency modulation.
      Currently, many brain-computer interface (BCI) systems have successfully helped
      patients with severe neuromuscular disabilities to regain independence. In order
      to translate this neural engineering success to hearing aid applications, we must
      be able to capture brain waves across the population reliably in cortical regions
      that have not previously been incorporated in these systems before, for example,
      dorsolateral prefrontal cortex (DLPFC) and right temporoparietal junction. Here,
      we present a brain-state classification framework that incorporates individual
      anatomical information and accounts for potential anatomical and functional
      differences across subjects by applying appropriate cortical weighting functions
      prior to the classification stage. Using an inverse imaging approach, use
      simulated EEG data to show that our method can outperform the traditional brain
      state classification approach that trains only on individual subject's data
      without considering data available at a population level. 

PMID- 24110312
TI  - Improving hearing aid fitting using the speech-evoked auditory brainstem
      response.
AB  - Measuring brain responses to speech may help improve the process of hearing aid
      fitting, especially in young children. Speech-evoked auditory brainstem responses
      (sABR) may be particularly useful because they provide a spectro-temporal
      representation of auditory neural activity in response to speech. However, use of
      the sABR in evaluating hearing aid performance has not been explored. This paper
      reviews recent work on measuring brain responses to speech, illustrates how sABR
      can provide insights into internal auditory processing, and proposes ways in
      which these responses may be used to improve hearing aid fitting. 

PMID- 24110313
TI  - Insect-machine hybrid system.
AB  - We demonstrated the remote control of insects in free flight via an implantable
      radio-equipped miniature neural stimulating system. This paper summarizes these
      results. The pronotum mounted system consisted of neural stimulators, muscular
      stimulators, a radio transceiver-equipped microcontroller and a microbattery.
      Flight initiation, cessation and elevation control were accomplished through
      neural stimulus of the brain which elicited, suppressed or modulated wing
      oscillation. Turns were triggered through the direct muscular stimulus of either
      of the basalar muscles. We characterized the response times, success rates, and
      free-flight trajectories elicited by our neural control systems in remotely
      controlled beetles. We believe this type of technology will open the door to in
      flight perturbation and recording of insect flight responses. 

PMID- 24110314
TI  - Hydrogel-based contractile electrodes for stimulation of cells and tissues.
AB  - We developed techniques for preparing a muscular cells-arrayed hydrogel sheet and
      a microelectrodes-printed hydrogel sheet. The combination of these two hydrogel
      sheets enables the metabolic assay for muscular tissue under a controlled
      contractile motion. 

PMID- 24110315
TI  - On-chip cellomics: Single-cell-based constructive cell-network assay for quasi-in
      vivo screening of cardiotoxicity.
AB  - We have developed methods and systems of analyzing epigenetic information in
      cells, as well as that of genetic information, to expand our understanding of how
      living systems are determined. A system of analyzing epigenetic information was
      developed starting from the twin complementary viewpoints of cell regulation as
      an 'algebraic' system (emphasis on temporal aspects) and as a 'geometric' system
      (emphasis on spatial aspects). As an example of the 'geometric' system, we have
      developed an quasi-in vivo hiPS cardiomyocyte network assay and confirmed that it
      can predict the risk of lethal arrythmia correctly in 22 compounds. The knowlege
      acquired from this study may lead to the use of cells that fully control
      practical applications like cell-based drug screening and the regeneration of
      organs. 

PMID- 24110316
TI  - Electroporation and electrofusion in field-tailored microstructures.
AB  - Bringing foreign substances into cells is a basic process in cell engineering. So
      called reversible breakdown of the cell membrane by electrical pulses opens up
      transient pores on the membrane through which molecules can diffuse into, or
      contacting cells can fuse. Using micro-fabricated structures with the dimension
      smaller than that of cells, the field pattern can be designed and tailored, that
      enables the handling of single cells, as well as the control over the location
      and the magnitude of the membrane voltage to achieve low invasive high-yield
      poration or fusion. This paper reviews some of our research, including gene
      transfection, electrofusion and cytoplasmic transplant. 

PMID- 24110317
TI  - Neuromuscular junction in a microfluidic device.
AB  - Malfunctions at the site of neuromuscular junction (NMJ) of post-injuries or
      diseases are major barriers to recovery of function. The ability to efficiently
      derive motor neurons (MN) from embryonic stem cells has indicated promise toward
      the development of new therapies in increasing functional outcomes post injury.
      Recent advances in micro-technologies have provided advanced culture platforms
      allowing compartmentalization of sub-cellular components of neurons. In this
      study, we combined these advances in science and technology to develop a
      compartmentalized in vitro NMJ model. The developed NMJ system is between mouse
      embryonic stem cell (mESC)-derived MNs and c2c12 myotubes cultured in a
      compartmentalized polydimethylsiloxane (PDMS) microfluidic device. While some
      functional in vitro NMJ systems have been reported, this system would further
      contribute to research in NMJ-related diseases by providing a system to study the
      site of action of NMJ aimed at improving promoting better functional recovery. 

PMID- 24110318
TI  - Postural stabilization by trunk tightening force generated by passive power
      assist device.
AB  - We are developing a passive power-assist supporter called Smart Suit Lite, which
      is a compact and lightweight power-assist device that utilizes the restoring
      force of elastic belts. Smart Suit Lite is designed not only to support muscles
      but also to stabilize the torso similarly to a corset. However, because a corset
      is always tight around the waist, negative effects caused by long-term use has
      been pointed out. In contrast, the tightening force generated by Smart Suit Lite
      increases only when the wearer adopts a posture corresponding to higher load on
      the low back. In this research, we performed two basic experiments to evaluate
      the static balance ability of wearers. As a result, the standard deviation of the
      lumbar angle decreased by 32.1% on average in wearers with low stability. 

PMID- 24110319
TI  - Development on smart suit for dairy work assistance.
AB  - Our purpose in this study is to achieve an independent life and a social
      involvement for the elderly using KEIROKA Technology(fatigue-reduction) which
      makes it possible to improve the quality of chores and occupations by removing
      excessive strain and tiredness. The authors have developed power assist suits
      named "smart suit". The authors have evaluated the effect that the purpose of
      dairy work assistance, to measure EMG of the worker, compared to the potential of
      the surface of the non-wearing and wearing "smart suit". 

PMID- 24110320
TI  - Improvement and quantitative performance estimation of the back support muscle
      suit.
AB  - We have been developing the wearable muscle suit for direct and physical motion
      supports. The use of the McKibben artificial muscle has opened the way to the
      introduction of "muscle suits" compact, lightweight, reliable, wearable "assist
      bots" enabling manual worker to lift and carry weights. Since back pain is the
      most serious problem for manual worker, improvement of the back support muscle
      suit under the feasibility study and quantitative estimation are shown in this
      paper. The structure of the upper body frame, the method to attach to the body,
      and the axes addition were explained as for the improvement. In the experiments,
      we investigated quantitative performance results and efficiency of the back
      support muscle suit in terms of vertical lifting of heavy weights by employing
      integral electromyography (IEMG). The results indicated that the values of IEMG
      were reduced by about 40% by using the muscle suit. 

PMID- 24110321
TI  - Powered orthosis and attachable power-assist device with Hydraulic Bilateral
      Servo System.
AB  - This paper discusses the developments and control strategies of exoskeleton-type
      robot systems for the application of an upper limb powered orthosis and an
      attachable power-assist device for care-givers. Hydraulic Bilateral Servo System,
      which consist of a computer controlled motor, parallel connected hydraulic
      actuators, position sensors, and pressure sensors, are installed in the system to
      derive the joint motion of the exoskeleton arm. The types of hydraulic component
      structure and the control strategy are discussed in relation to the design
      philosophy and target joints motions. 

PMID- 24110322
TI  - Novel compliant actuator for wearable robotics applications.
AB  - In the growing fields of wearable robotics, rehabilitation robotics, prosthetics,
      and walking robots, variable impedance and force actuators are being designed and
      implemented because of their ability to dynamically modulate the intrinsic
      viscoelastic properties such as stiffness and damping. This modulation is crucial
      to achieve an efficient and safe human-robot interaction that could lead to
      electronically generate useful emergent dynamical behaviors. In this work we
      propose a novel actuation system in which is implemented a control scheme based
      on equilibrium forces for an active joint capable to provide
      assistance/resistance as needed and also achieve minimal mechanical impedance
      when tracking the movement of the user limbs. The actuation system comprises a DC
      motor with a built in speed reducer, two force-sensing resistors (FSR), a
      mechanism which transmits to the FSRs the torque developed in the joint and a
      controller which regulate the amount of energy that is delivered to the DC motor.
      The proposed system showed more impedance reduction, by the effect of the
      controlled contact forces, compared with the ones in the reviewed literature. 

PMID- 24110323
TI  - Daily life event segmentation for lifestyle evaluation based on multi-sensor data
      recorded by a wearable device.
AB  - In order to evaluate people's lifestyle for health maintenance, this paper
      presents a segmentation method based on multi-sensor data recorded by a wearable
      computer called eButton. This device is capable of recording more than ten hours
      of data continuously each day in multimedia forms. Automatic processing of the
      recorded data is a significant task. We have developed a two-step summarization
      method to segment large datasets automatically. At the first step, motion sensor
      signals are utilized to obtain candidate boundaries between different daily
      activities in the data. Then, visual features are extracted from images to
      determine final activity boundaries. It was found that some simple signal
      measures such as the combination of a standard deviation measure of the gyroscope
      sensor data at the first step and an image HSV histogram feature at the second
      step produces satisfactory results in automatic daily life event segmentation.
      This finding was verified by our experimental results. 

PMID- 24110324
TI  - Accurate and continuous non-contact vital signs monitoring using phased array
      antennas in a clutter-free anechoic chamber.
AB  - Continuous and accurate monitoring of human vital signs is an important part of
      the healthcare industry, as it is the basic means by which the clinicians can
      determine the instantaneous status of their patients. Doppler-based noncontact
      vital signs (NCVS) sensor systems can monitor the heart and respiration rates
      without touching the patient, but it has been observed that that the accuracy of
      these NCVS sensors can be diminished by reflections from background clutters in
      the measurement environment, and that high directivity antennas can increase the
      sensing accuracy. Therefore, this work explores a NCVS sensor with continuous
      data taken inside an anechoic chamber where the background cluttering is
      negligible. In addition, a high directivity custom-made beam-steerable phased
      array antenna system is used to improve the performance and functionality of the
      2.4GHz NCVS sensor we have built. We believe this work is the 1st systematic
      study using Doppler-based phased array systems for NCVS sensing performed in a
      clutter-free anechoic chamber. 

PMID- 24110325
TI  - Comparing metabolic energy expenditure estimation using wearable multi-sensor
      network and single accelerometer.
AB  - This paper presents the implementation details, system architecture and
      performance of a wearable sensor network that was designed for human activity
      recognition and energy expenditure estimation. We also included ActiGraph GT3X+
      as a popular single sensor solution for detailed comparison with the proposed
      wearable sensor network. Linear regression and Artificial Neural Network are
      implemented and tested. Through a rigorous system study and experiment, it is
      shown that the wearable multi-sensor network outperforms the single sensor
      solution in terms of energy expenditure estimation. 

PMID- 24110326
TI  - The effect of emotion on keystroke: an experimental study using facial feedback
      hypothesis.
AB  - The automatic emotion recognition technology is an important part of building
      intelligent systems to prevent the computers acting inappropriately. A novel
      approach for recognizing emotional state by their keystroke typing patterns on a
      standard keyboard was developed in recent years. However, there was very limited
      investigation about the phenomenon itself in the previous literatures. Hence, in
      our study, we conduct a controlled experiment to collect subjects' keystroke data
      in the different emotional states induced by facial feedback. We examine the
      difference of the keystroke data between positive and negative emotional states.
      The results prove the significance in the differences in the typing patterns
      under positive and negative emotions for all subjects. Our study provides an
      evidence for the reasonability about developing the technique of emotion
      recognition by keystroke. 

PMID- 24110327
TI  - Ultra-low-cost clinical pulse oximetry.
AB  - An ultra-low-cost pulse oximeter is presented that interfaces a conventional
      clinical finger sensor with a mobile phone through the headset jack audio
      interface. All signal processing is performed using the audio subsystem of the
      phone. In a preliminary volunteer study in a hypoxia chamber, we compared the
      oxygen saturation obtained with the audio pulse oximeter against a commercially
      available (and FDA approved) reference pulse oximeter (Nonin Xpod). Good
      agreement was found between the outputs of the two devices. 

PMID- 24110328
TI  - Exercise amount calculation using a wearable half-cell potential sensor for
      mobile aerobic exercise management.
AB  - The obesity has grown to concerning proportions in recent years, and it causes
      heart disease, type 2 diabetes, breast cancer, and colon cancer. To get healthy
      weight, commercial wearable devices with a accelerometer have been released to
      help users to quantitatively manage calories. However, an accelerometer has
      disadvantages: large power consumption and expensive price. We suggested a new
      method to measure the exercise amount using a HCP sensor. We performed an
      experiment to compare accuracies of exercise amount estimation using a HCP sensor
      with using an accelerometer with five subjects, and the accuracy of the HCP
      sensor was comparable to it of the accelerometer. Since a HCP sensor has lower
      power consumption and cheaper price than an accelerometer, wearable sensor can be
      smaller and cheaper than current commercial devices. 

PMID- 24110329
TI  - Single-trial detection of visual evoked potentials by common spatial patterns and
      wavelet filtering for brain-computer interface.
AB  - Event-related potentials (ERPs) are widely used in brain-computer interface (BCI)
      systems as input signals conveying a subject's intention. A fast and reliable
      single-trial ERP detection method can be used to develop a BCI system with both
      high speed and high accuracy. However, most of single-trial ERP detection methods
      are developed for offline EEG analysis and thus have a high computational
      complexity and need manual operations. Therefore, they are not applicable to
      practical BCI systems, which require a low-complexity and automatic ERP detection
      method. This work presents a joint spatial-time-frequency filter that combines
      common spatial patterns (CSP) and wavelet filtering (WF) for improving the signal
      to-noise (SNR) of visual evoked potentials (VEP), which can lead to a single
      trial ERP-based BCI. 

PMID- 24110330
TI  - Uniform approximation of Gaussian wavelet for biomedical signal processing in
      analog domain.
AB  - Signal processing in analog domain is favorable when power consumption is a
      critical design constraint. Continuous Wavelet Transform (CWT), which is
      increasingly being used in characterizing biomedical signals, when implemented in
      analog domain consumes less power provided the mother wavelet is properly
      approximated. This paper presents an approximation of Gaussian wavelet by making
      use of the Uniform approximation. Simulations of the approximated wavelet and the
      actual wavelet in MATLAB are performed and the results discussed. Simulations
      show that (i) approximation obtained closely matches the mother wavelet chosen
      and (ii) a stable approximation which helps in physical realization using any
      circuit design methodology. 

PMID- 24110331
TI  - Wavelet packet analysis of EEG signals from dyslexic children with writing
      disability.
AB  - This paper describes Wavelet Packet Analysis of EEG signal of dyslexic children
      with writing disability. Two activities were carried out during EEG recordings;
      relax and and writing letters. EEG signals were collected using biosignal
      gMobilab system and analysed using Wavelet Packet Decomposition to extract alpha
      and beta brainwave rhythm. Statistical data such as log energy entropy and
      standard deviation were used to compare the characteristic of EEG signals from
      dyslexic and normal children. Result showed that the dyslexic children consumed
      higher energy at left parietal lobe during writing activity especially those who
      write incorrectly. The alpha band shows higher log energy entropy for dyslexic
      children compare to normal children at most channel during relax. 

PMID- 24110332
TI  - Estimation of temporal scales of variation in long-term scalp
      electroencephalograms from epilepsy patients.
AB  - Long-term neurophysiological recordings, such as scalp encephalograms (EEG), have
      been routinely used in studies that aim to characterize dynamic changes in brain
      activity associated with normal biological processes, such as sleep, but are also
      becoming increasingly common for clinical evaluation of patients with
      neurological disorders, such as epilepsy. Analysis of non-stationary recordings
      from multiple days poses new signal processing challenges, in regard to algorithm
      efficiency and computational cost, as well as adequate dimensionality data
      reduction. We compared four approaches for estimating the underlying temporal
      dynamics of long-term recordings from patients with medically refractory
      epilepsy: (i) model order selection using the minimum description length
      principle, (ii) approximate entropy, (iii) mutual information, and (iv) Detrended
      Fluctuation Analysis (DFA). Individual approaches were found to be sensitive only
      to specific scales of variation. Approximate entropy and mutual information were
      sensitive to local dynamics, whereas dynamic model order estimation captured only
      slowly varying dynamics. DFA was sensitive to multiple temporal scales. 

PMID- 24110333
TI  - Scattering transform for intrapartum fetal heart rate characterization and
      acidosis detection.
AB  - Early acidosis detection and asphyxia prediction in intrapartum fetal heart rate
      is of major concern. This contribution aims at assessing the potential of the
      Scattering Transform to characterize intrapartum fetal heart rate. Elaborating on
      discrete wavelet transform, the Scattering Transform performs a non linear and
      multiscale analysis, thus probing not only the covariance structure of data but
      also the full dependence structure. Applied to a real database constructed by a
      French public academic hospital, the Scattering Transform is shown to catch
      relevant features of intrapartum fetal heart rate time dynamics and to have a
      satisfactory ability to discriminate Normal subjects from Abnormal. 

PMID- 24110334
TI  - Probabilistic estimation of respiratory rate using Gaussian processes.
AB  - The presence of respiratory information within the electrocardiogram (ECG) signal
      is a well-documented phenomenon. We present a Gaussian process framework for the
      estimation of respiratory rate from the different sources of modulation in a
      single-lead ECG. We propose a periodic covariance function to model the frequency
      and amplitude-modulation time series derived from the ECG, where the
      hyperparameters of the process are used to derive the respiratory rate. The
      approach is evaluated using data taken from 40 healthy subjects each with 2 hours
      of monitoring, containing ECG and respiration waveforms. Results indicate that
      the accuracy of our proposed method is comparable with that of existing methods,
      but with the advantages of a principled probabilistic approach, including the
      direct quantification of the uncertainty in the estimation. 

PMID- 24110335
TI  - Robust spectral analysis of thoraco-abdominal motion and oxymetry in obstructive
      sleep apnea.
AB  - The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography (PSG), a
      multidimensional biosignal recording that is conducted in sleep laboratories.
      Standard PSG montage involves the use of nasal-oral airflow sensors to visualize
      cyclic episodes of upper airflow interruption, which are considered diagnostic of
      sleep apnea. Given the high-cost and discomfort associated with in-laboratory
      PSG, there is an emergent need for novel technology that simplifies OSA screening
      and diagnosis with less expensive methods. The main goal of this project was to
      identify novel OSA signatures based on the spectral analysis of thoraco-abdominal
      motion channels. Our main hypothesis was that proper spectral analysis can detect
      OSA cycles in adults using simultaneous recording of oxygen saturation (SaO2) and
      either, chest or abdominal motion. A sample study on 35 individuals was conducted
      with statistically significant results that suggest a strong relationship between
      airflow-independent signals and oxygen saturation. The impact of this new
      approach is that it may allow the design of more comfortable and reliable
      portable devices for screening, diagnosis and monitoring of OSA, functioning only
      with oximetry and airflow-independent (abdominal or chest) breathing sensors. 

PMID- 24110336
TI  - Driver-response relationships between frontal EEG and respiration during
      affective audiovisual stimuli.
AB  - The complementary nature and the coordinative tendencies of brain and body are
      essential to the way humans function. Although static features from brain and
      body signals have been shown to reflect emotions, the dynamic interrelation of
      the two systems during emotional processes is still in its infancy. This study
      aims at investigating the way brain signals captured by Electroencephalography
      (EEG) and bodily responses reflected in respiration interact when watching music
      clips. A non-linear measure is applied to frontal EEG and respiration to
      determine the driver/driven relationship between these two modalities. The
      results reveal a unidirectional dependence from respiration to EEG which adds
      evidence to the bodily-feedback theory. 

PMID- 24110337
TI  - Vectorcardiographic loop alignment for fetal movement detection using the
      expectation-maximization algorithm and support vector machines.
AB  - Reduced fetal movement is an important parameter to assess fetal distress.
      Currently, no suitable methods are available that can objectively assess fetal
      movement during pregnancy. Fetal vectorcardiographic (VCG) loop alignment could
      be such a method. In general, the goal of VCG loop alignment is to correct for
      motion-induced changes in the VCGs of (multiple) consecutive heartbeats. However,
      the parameters used for loop alignment also provide information to assess fetal
      movement. Unfortunately, current methods for VCG loop alignment are not robust
      against low-quality VCG signals. In this paper, a more robust method for VCG loop
      alignment is developed that includes a priori information on the loop alignment,
      yielding a maximum a posteriori loop alignment. Classification, based on movement
      parameters extracted from the alignment, is subsequently performed using support
      vector machines, resulting in correct classification of (absence of) fetal
      movement in about 75% of cases. After additional validation and optimization,
      this method can possibly be employed for continuous fetal movement monitoring. 

PMID- 24110338
TI  - Estimation of glance from EEG for cursor control.
AB  - The variations in the electrooculogram (EOG) caused by eye motion are roughly
      proportional to the instantaneous horizontal and vertical glance angle. This
      linear correlation is exploited in systems using EOG to control software, and
      hardware such as artificial limbs, or wheelchairs. In these approaches, the drift
      in the electronics is commonly compensated by applying a high-pass filter.
      Consequently, the remaining EOG signal contains only blinks and rapid eye
      movement. However, repeating these eye gestures voluntarily is exhausting. This
      paper presents an algorithm that estimates the instantaneous glance of a subject
      from EEG signals. The subject is seated in front of a computer screen to control
      an application by glance. Because the visual field of interest, in this setting,
      is the limited area of the monitor, we can compensate the error in the glance
      estimate by detecting outliers. Because no high-pass filter is applied to the
      data, the user controls the applications by eye glance, which is comfortable and
      can be performed over extended periods of time. The numerical evaluation of the
      experiments with 12 volunteers, and video recordings of EOG controlled
      applications demonstrate the accuracy of our algorithm. 

PMID- 24110339
TI  - Variations in respiratory sounds in relation to fluid accumulation in the upper
      airways.
AB  - Obstructive sleep apnea (OSA) is a common disorder due to recurrent collapse of
      the upper airway (UA) during sleep that increases the risk for several
      cardiovascular diseases. Recently, we showed that nocturnal fluid accumulation in
      the neck can narrow the UA and predispose to OSA. Our goal is to develop non
      invasive methods to study the pathogenesis of OSA and the factors that increase
      the risks of developing it. Respiratory sound analysis is a simple and non
      invasive way to study variations in the properties of the UA. In this study we
      examine whether such analysis can be used to estimate the amount of neck fluid
      volume and whether fluid accumulation in the neck alters the properties of these
      sounds. Our acoustic features include estimates of formants, pitch, energy,
      duration, zero crossing rate, average power, Mel frequency power, Mel cepstral
      coefficients, skewness, and kurtosis across segments of sleep. Our results show
      that while all acoustic features vary significantly among subjects, only the
      variations in respiratory sound energy, power, duration, pitch, and formants
      varied significantly over time. Decreases in energy and power over time accompany
      increases in neck fluid volume which may indicate narrowing of UA and
      consequently an increased risk of OSA. Finally, simple discriminant analysis was
      used to estimate broad classes of neck fluid volume from acoustic features with
      an accuracy of 75%. These results suggest that acoustic analysis of respiratory
      sounds might be used to assess the role of fluid accumulation in the neck on the
      pathogenesis of OSA. 

PMID- 24110340
TI  - Identification of recurring wavefront propagation patterns in atrial fibrillation
      using basis pursuit.
AB  - High density contact electrogram data of atrial fibrillation (AF) contain
      detailed information on recurring activation patterns and dominant signaling
      pathways. Current methods to analyze these patterns and pathways rely mainly on
      supervised atrial deflection annotation and wave reconstruction. In this study,
      we developed a new algorithm to automatically identify recurring patterns and
      dominant pathways without the need for annotation. A sparse multivariate
      autoregression model was estimated on short segments of synchronous unipolar
      electrograms to extract the dominant interactions between electrograms at
      different recording electrodes. Sparsity of the electrode interaction matrices at
      several time-lags was maximized by applying a distance-weighted basis pursuit
      algorithm. Dominant interactions were identified by computing the mean
      interaction matrix over a number of consecutive time segments. The algorithm was
      evaluated on high-density recordings with 234 electrodes and 2.4mm electrode
      spacing in the left and right atrial free wall of a goat model of AF. The method
      was able to identify relevant patterns of AF, including wave trains, repetitive
      breakthrough waves and rotating wave activity. 

PMID- 24110341
TI  - A new statistical approach for the extraction of adjacency matrix from effective
      connectivity networks.
AB  - Graph theory is a powerful mathematical tool recently introduced in neuroscience
      field for quantitatively describing the main properties of investigated
      connectivity networks. Despite the technical advancements provided in the last
      few years, further investigations are needed for overcoming actual limitations in
      the field. In fact, the absence of a common procedure currently applied for the
      extraction of the adjacency matrix from a connectivity pattern has been leading
      to low consistency and reliability of ghaph indexes among the investigated
      population. In this paper we proposed a new approach for adjacency matrix
      extraction based on a statistical threshold as valid alternative to empirical
      approaches, extensively used in Neuroscience field (i.e. fixing the edge
      density). In particular we performed a simulation study for investigating the
      effects of the two different extraction approaches on the topological properties
      of the investigated networks. In particular, the comparison was performed on two
      different datasets, one composed by uncorrelated random signals (null-model) and
      the other one by signals acquired on a mannequin head used as a phantom (EEG null
      model). The results highlighted the importance to use a statistical threshold for
      the adjacency matrix extraction in order to describe the real existing
      topological properties of the investigated networks. The use of an empirical
      threshold led to an erroneous definition of small-world properties for the
      considered connectivity patterns. 

PMID- 24110342
TI  - Advanced methods for time-varying effective connectivity estimation in memory
      processes.
AB  - Memory processes are based on large cortical networks characterized by non
      stationary properties and time scales which represent a limitation to the
      traditional connectivity estimation methods. The recent development of
      connectivity approaches able to consistently describe the temporal evolution of
      large dimension connectivity networks, in a fully multivariate way, represents a
      tool that can be used to extract novel information about the processes at the
      basis of memory functions. In this paper, we applied such advanced approach in
      combination with the use of state-of-the-art graph theory indexes, computed on
      the connectivity networks estimated from high density electroencephalographic
      (EEG) data recorded in a group of healthy adults during the Sternberg Task. The
      results show how this approach is able to return a characterization of the main
      phases of the investigated memory task which is also sensitive to the increased
      length of the numerical string to be memorized. 

PMID- 24110343
TI  - A tensorial approach to access cognitive workload related to mental arithmetic
      from EEG functional connectivity estimates.
AB  - The association of functional connectivity patterns with particular cognitive
      tasks has long been a topic of interest in neuroscience, e.g., studies of
      functional connectivity have demonstrated its potential use for decoding various
      brain states. However, the high-dimensionality of the pairwise functional
      connectivity limits its usefulness in some real-time applications. In the present
      study, the methodology of tensor subspace analysis (TSA) is used to reduce the
      initial high-dimensionality of the pairwise coupling in the original functional
      connectivity network to a space of condensed descriptive power, which would
      significantly decrease the computational cost and facilitate the differentiation
      of brain states. We assess the feasibility of the proposed method on EEG
      recordings when the subject was performing mental arithmetic task which differ
      only in the difficulty level (easy: 1-digit addition v.s. 3-digit additions). Two
      different cortical connective networks were detected, and by comparing the
      functional connectivity networks in different work states, it was found that the
      task-difficulty is best reflected in the connectivity structure of sub-graphs
      extending over parietooccipital sites. Incorporating this data-driven information
      within original TSA methodology, we succeeded in predicting the difficulty level
      from connectivity patterns in an efficient way that can be implemented so as to
      work in real-time. 

PMID- 24110344
TI  - Time-varying correlation coefficients estimation and its application to dynamic
      connectivity analysis of fMRI.
AB  - Exploration of the dynamics of functional brain connectivity based on the
      correlation coefficients of functional magnetic resonance imaging (fMRI) data is
      important for understanding the brain mechanisms. Because fMRI data are time
      varying in nature, the functional connectivity shows substantial fluctuations and
      dynamic characteristics. However, an effective method for estimating time-varying
      functional connectivity is lacking, which is mainly due to the difficulty in
      choosing an appropriate window to localize the time-varying correlation
      coefficients (TVCC). This paper introduces a novel method for adaptively
      estimating the TVCC of non-stationary signals and studies its application to
      infer dynamic functional connectivity of fMRI data in a visual task. The proposed
      method employs a sliding window having a certain bandwidth to estimate the TVCC
      locally and the window bandwidths are selected adaptively by a local plug-in rule
      to minimize the mean squared error. The results show that the functional
      connectivity changes in the visual task are transient, which suggests that simply
      assuming sustained connectivity changes during task period might not be
      sufficient to capture dynamic connectivity changes induced by tasks. 

PMID- 24110345
TI  - Functional dependence in the human brain: a graph theoretical analysis.
AB  - In this paper, we propose a graph-theoretical approach to reveal patterns of
      functional dependencies between different scalp regions. We start by computing
      pairwise measures of dependence from dense-array scalp electroencephalographic
      (EEG) recordings. The obtained dependence matrices are then averaged over trials
      and further statistically processed to provide more reliability. Graph structure
      information is subsequently extracted using several graph theoretical measures.
      Simple measures of node degree and clustering strength are shown to be useful to
      describe the global properties of the analyzed networks. More sophisticated
      measures, such as betweenness centrality and subgraph centrality tend to provide
      additional insight into the network structure, and therefore robustly
      discriminate two cognitive states. We further examine the connected components of
      the graph to identify the dependent functional regions. The approach supports
      dynamicity in that all suggested computations can be easily extended to different
      points in time, thus enabling to monitor dependence evolution and variability
      with time. 

PMID- 24110346
TI  - Magnetic resonance tracking of catheters and mechatronic devices operating in the
      vascular network with an embedded photovoltaic-based microelectronic circuit.
AB  - Tracking of a catheter through the arterial system is critical in several medical
      interventions. To avoid excessive dose of x-ray irradiation, Magnetic Resonance
      Imaging (MRI) has been proposed. In such a case, a simple ferromagnetic sphere
      placed at the tip of the catheter could be used. However, due to the artifact
      created by the ferromagnetic core, it becomes impossible to gather an image of
      the tissues surrounding such a marker. Hence, in this paper we propose replacing
      the ferromagnetic marker with a microchip containing a coil and a photovoltaic
      cell. By radiating light to the photovoltaic cell, the coil generates a magnetic
      field which is detected as an artifact in MR images. By turning off the light,
      the effect of the coil is eliminated allowing images of tissues next to the
      marker to be taken. In this paper, simulated results based on experimental data
      from the preliminary designs suggest that this approach could be viable not only
      for catheters but also, it could potentially be used in various tools as well as
      mechatronic devices being moved inside the body. 

PMID- 24110347
TI  - Anisotropic diffusion filtering for correlated multiple-coil MRI.
AB  - Recently, some methods have been proposed for filtering multi-coil MRI
      acquisitions with correlation between coils. Those methods are based on
      statistical models of noise to develop a Linear Minimum Mean Square Error (LMMSE)
      filter. The advantage of LMMSE-based filters stems from their simplicity and
      robustness. However, they exhibit some drawbacks: their performance strongly
      depends on the underlying statistical model and on the way the local moments are
      estimated. The first problem can be avoided when considering effective values
      provided by recent studies on the models of noise in multi-coil systems with
      correlation between coils. However, the local moments are estimated in square
      neighborhoods which can include different kinds of tissues. Thus, the local
      variance is biased towards upper values, which results in an inaccurate estimate
      in regions close to tissue boundaries. In this work we propose to overcome this
      problem by introducing an anisotropic diffusion step in the LMMSE estimate for
      correlated multi-coil systems which improves the estimation of the signal in
      regions where other LMMSE methods fail. Results demonstrate the better behavior
      in different noisy scenarios. 

PMID- 24110348
TI  - Localization of brachytherapy seeds in MRI by deconvolution.
AB  - MRI has the potential to be used as a preferred imaging method for brachytherapy
      during the seed insertion and post-surgery evaluation. However, the brachytherapy
      seeds usually appear dark in the MRI magnitude images. Previously, we have
      developed a method based on susceptibility mapping to generate positive contrast
      of the seeds, which allows improved seed localization. In this paper, we propose
      a new method to localize the seeds by deconvolution using a seed kernel (i.e. the
      calculated magnetic field surrounding a seed). The deconvolution is solved using
      a regularized L1 minimization. Results from simulated and experimental data sets
      show that the seeds can be identified and localized using the proposed method
      more precisely. 

PMID- 24110349
TI  - Towards a Hall effect magnetic tracking device for MRI.
AB  - This paper presents the first prototype of a magnetic tracking device for
      Magnetic Resonance Imaging. The unique relationship between the space coordinates
      of a MRI scanner bore and the magnetic field gradients used in MRI allows
      building a localization system based on an accurate measurement of these
      gradients. These gradients are measured thanks to a 3D Hall device with a
      footprint of only 50um(2), integrated with its specific conditioning circuit in a
      low cost, low voltage 0.35um CMOS process. The first experimental results show
      that a sub-millimeter localization is possible. It opens the way to the
      development of MRI compatible magnetic tracking systems integrable in a surgical
      tool. 

PMID- 24110350
TI  - Evaluation of an image-based tracking workflow with Kalman filtering for
      automatic image plane alignment in interventional MRI.
AB  - Recently, a workflow for magnetic resonance (MR) image plane alignment based on
      tracking in real-time MR images was introduced. The workflow is based on a
      tracking device composed of 2 resonant micro-coils and a passive marker, and
      allows for tracking of the passive marker in clinical real-time images and
      automatic (re-)initialization using the microcoils. As the Kalman filter has
      proven its benefit as an estimator and predictor, it is well suited for use in
      tracking applications. In this paper, a Kalman filter is integrated in the
      previously developed workflow in order to predict position and orientation of the
      tracking device. Measurement noise covariances of the Kalman filter are
      dynamically changed in order to take into account that, according to the image
      plane orientation, only a subset of the 3D pose components is available. The
      improved tracking performance of the Kalman extended workflow could be quantified
      in simulation results. Also, a first experiment in the MRI scanner was performed
      but without quantitative results yet. 

PMID- 24110351
TI  - Hyperpolarized (129)Xe spectra from C6 glioma cells implanted in rat brains.
AB  - Tumor cell density is dramatically different from normal tissue. Since the
      chemical shift of hyperpolarized (129)Xe reflects local cell structure, we
      hypothesized that the presence of tumor cells could potentially be determined
      from (129)Xe spectra. Spectra and washout decay rate from three rats implanted
      with C6 glioma cells were compared with eight control rats. No significant
      differences between normal and tumor spectra were observed. The decay time of the
      C6 rats (mean 13.5 +/- 1.9 s) was not significantly different from normal rats
      (mean 11.7 +/- 1.8 s). These results suggest that hyperpolarized Xe may not be a
      superior tracer for detection of tumor cells in the intact brain. 

PMID- 24110352
TI  - Reconstructing patient-specific cardiac models from contours via Delaunay
      triangulation and graph-cuts.
AB  - This study proposes a novel method to reconstruct the left cardiac structure from
      contours. Given the contours representing left ventricle (LV), left atrium (LA),
      and aorta (AO), re-orientation, contour matching, extrapolation, and
      interpolation are performed sequentially. The processed data are then
      reconstructed via a variational method. The weighted minimal surface model is
      revised to handle the multi-phase cases, which happens at the LV-LA-AO junction.
      A Delaunay-based tetrahedral mesh is generated to discretize the domain while the
      max-flow/min-cut algorithm is utilized as the minimization tool. The
      reconstructed model including LV, LA, and AO structure is extracted from the mesh
      and post-processed further. Numerical examples show the robustness and
      effectiveness of the proposed method. 

PMID- 24110353
TI  - Optimization of surgical planning of total hip arthroplasty based on
      computational anatomy.
AB  - This paper describes a method for automated optimization of total hip
      arthroplasty (THA) planning incorporating joint functionalities. The optimal
      planning is formulated as maximum a posterior (MAP) estimation, which ensures the
      best-balance of joint functionalities and bone-implant spatial relations based on
      their statistical models derived from the training datasets prepared by an
      experienced surgeon. According to the performance evaluation, four of the six
      functionalities of the automatically optimized plans were almost equivalent to
      those of surgeon's plans, and two of them were improved. We consider these
      results showed a potential usefulness of the proposed method. 

PMID- 24110355
TI  - Automated method for extraction of lung tumors using a machine learning
      classifier with knowledge of radiation oncologists on data sets of planning CT
      and FDG-PET/CT images.
AB  - We have developed an automated method for extraction of lung tumors using a
      machine learning classifier with knowledge of radiation oncologists on data sets
      of treatment planning computed tomography (CT) and 18F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET)/CT images. First, the PET images were
      registered with the treatment planning CT images through the diagnostic CT images
      of PET/CT. Second, six voxel-based features including voxel values and magnitudes
      of image gradient vectors were derived from each voxel in the planning CT and PET
      /CT image data sets. Finally, lung tumors were extracted by using a support
      vector machine (SVM), which learned 6 voxel-based features inside and outside
      each true tumor region determined by radiation oncologists. The results showed
      that the average DSCs for 3 and 6 features for three cases were 0.744 and 0.899,
      and thus the SVM may need 6 features to learn the distinguishable
      characteristics. The proposed method may be useful for assisting treatment
      planners in delineation of the tumor region. 

PMID- 24110354
TI  - Computerized segmentation of liver in hepatic CT and MRI by means of level-set
      geodesic active contouring.
AB  - Computerized liver volumetry has been studied, because the current "gold
      standard" manual volumetry is subjective and very time-consuming. Liver volumetry
      is done in either CT or MRI. A number of researchers have developed computerized
      liver segmentation in CT, but there are fewer studies on ones for MRI. Our
      purpose in this study was to develop a general framework for liver segmentation
      in both CT and MRI. Our scheme consisted of 1) an anisotropic diffusion filter to
      reduce noise while preserving liver structures, 2) a scale-specific gradient
      magnitude filter to enhance liver boundaries, 3) a fast-marching algorithm to
      roughly determine liver boundaries, and 4) a geodesic-active-contour model
      coupled with a level-set algorithm to refine the initial boundaries. Our CT
      database contained hepatic CT scans of 18 liver donors obtained under a liver
      transplant protocol. Our MRI database contains 23 patients with 1.5T MRI
      scanners. To establish "gold-standard" liver volumes, radiologists manually
      traced the contour of the liver on each CT or MR slice. We compared our computer
      volumetry with "gold-standard" manual volumetry. Computer volumetry in CT and MRI
      reached excellent agreement with manual volumetry (intra-class correlation
      coefficient = 0.94 and 0.98, respectively). Average user time for computer
      volumetry in CT and MRI was 0.57 +/- 0.06 and 1.0 +/- 0.13 min. per case,
      respectively, whereas those for manual volumetry were 39.4 +/- 5.5 and 24.0 +/-
      4.4 min. per case, respectively, with statistically significant difference (p <
      .05). Our computerized liver segmentation framework provides an efficient and
      accurate way of measuring liver volumes in both CT and MRI. 

PMID- 24110356
TI  - Development of a numerical simulator of human swallowing using a particle method
      (Part 2. Evaluation of the accuracy of a swallowing simulation using the 3D MPS
      method).
AB  - The aim of this study was to develop and evaluate the accuracy of a three
      dimensional (3D) numerical simulator of the swallowing action using the 3D moving
      particle simulation (MPS) method, which can simulate splashes and rapid changes
      in the free surfaces of food materials. The 3D numerical simulator of the
      swallowing action using the MPS method was developed based on accurate organ
      models, which contains forced transformation by elapsed time. The validity of the
      simulation results were evaluated qualitatively based on comparisons with
      videofluorography (VF) images. To evaluate the validity of the simulation results
      quantitatively, the normalized brightness around the vallecula was used as the
      evaluation parameter. The positions and configurations of the food bolus during
      each time step were compared in the simulated and VF images. The simulation
      results corresponded to the VF images during each time step in the visual
      evaluations, which suggested that the simulation was qualitatively correct. The
      normalized brightness of the simulated and VF images corresponded exactly at all
      time steps. This showed that the simulation results, which contained information
      on changes in the organs and the food bolus, were numerically correct. Based on
      these results, the accuracy of this simulator was high and it could be used to
      study the mechanism of disorders that cause dysphasia. This simulator also
      calculated the shear rate at a specific point and the timing with Newtonian and
      non-Newtonian fluids. We think that the information provided by this simulator
      could be useful for development of food products, medicines, and in
      rehabilitation facilities. 

PMID- 24110357
TI  - Navigation system with real-time finite element analysis for minimally invasive
      surgery.
AB  - This paper presents a navigation system for minimally invasive surgery,
      especially laparoscopic surgery in which operates in abdomen. Conventional
      navigation systems show virtual images by superimposing models of target tissues
      on real endoscopic images. Since soft tissues within the abdomen are deformed
      during the surgery, the navigation system needs to provide surgeons reliable
      information by deforming the models according to their biomechanical behavior.
      However, conventional navigation systems don't consider the tissue deformation
      during the surgery. We have been developing a new real-time FEM-based simulation
      for deforming a soft tissue model by using neural network[1]. The network is
      called the neuroFEM. The incorporation of the neuroFEM into the navigation leads
      to improve the accuracy of the navigation system. In this paper, we propose a new
      navigation system with a framework of the neuroFEM. 

PMID- 24110358
TI  - Reconstruction of missing cells by a Killing energy minimizing nonrigid image
      registration.
AB  - Fluorescent microscopy has been a popular and important tool for studying live
      cells. One challenge of analyzing cell images obtained from fluorescent
      microscopy is that cells in fluorescent images frequently disappear and reappear,
      making cell tracking difficult. In this paper, we present an image registration
      approach which can reconstruct both the cell appearance and location of the
      missing cells from the image frames where the cells become invisible. The idea is
      to perform an image registration on the images before and after a cell
      disappears. The missing image frames between these two images are given by the
      intermediate registration results. The formulation is based on the nonrigid
      particle registration model, which captures soft deformation of the cells. In
      addition, to obtain natural and more rigid cell movements such as translation and
      rotation, we propose a new registration technique which is Killing energy
      minimizing, motivated by the fact that a Killing vector field with zero Killing
      energy will generate an isometric deformation. We will present reconstruction
      results of C2C12 cells in fluorescent images to illustrate the effectiveness of
      our model by different numerical examples. 

PMID- 24110359
TI  - Automated analysis of zebrafish images for screening toxicants.
AB  - An important factor facilitating the application of zebrafish in biomedical
      research is high throughput screening of vertebrate animal models. For example,
      being able to model the growth of blood vessel in the vasculature system is
      interesting for understanding both the circulatory system in humans, and for
      facilitating large scale screening of the influence of various chemicals on
      vascular development. Compared to other models, the zebrafish embryo is an
      attractive alternative for environmental risk assessment of chemicals since it
      offers the possibility to perform high-throughput analyses in vivo. However the
      lack of an automated image analysis framework restricts high throughput
      screening. In this paper, we provide a method for quantitative measurements of
      zebrafish blood vessel morphology since it is difficult to assess changes in
      vessel structure by visual inspection. The method presented is generalized, i.e.
      it is not restricted to any specific chemically treated zebrafish, and can be
      used with wide variety of chemicals. 

PMID- 24110360
TI  - Analysis of the rotational center location method in Optical Projection
      Tomography.
AB  - In Optical Projection Tomography (OPT), if the rotational center deviates from
      the central line of the image and this offset is not corrected during the
      reconstruction, serious blurring will happen in the final 3-dimensional (3D)
      result. Therefore, the high-precision rotational center location method is very
      important for OPT. However, existing methods are inconvenient because they need
      active participation during the location process. Thus, the automated and fast
      rotational center location method is in great demand. In preliminary work, we
      proposed an automated rotational center location method which consisted of a high
      Specimen Signal Intensity (SSI) sinogram selection and a coarse-fine search. Our
      method had an accuracy of about 1/4 pixel. However, further robustness analysis
      of our method is lacking. In this paper, we have investigated its location errors
      on sinograms with various SSIs and analyzed whether it was effective to use high
      SSI sinograms for rotational center location. Moreover, we have also discussed
      the relationship between location errors and the starting rotational angles. The
      experimental results showed that our coarse-fine method was robust under
      different starting angles. Meanwhile, the high SSI sinogram selection scheme
      improved the location precision. 

PMID- 24110361
TI  - Unmixing of spectrally similar quantum dots using filter selection.
AB  - This paper explores the possibilities for quantitative analysis of multiplexed
      Quantum Dot Immunohistochemical (QDIHC) staining using a 10-slot fluorescence
      microscope filter wheel. QDs are an ideal fluorophore for staining biomarkers due
      to their unique properties, including greater photostability and relatively
      narrower emission bandwidths compared to organic dyes. We imaged a slide
      containing 5 pure QD spots and 6 QD mixtures with a customized scanning
      fluorescence microscope. The QD mixtures contained either two or three QDs in
      equal amounts. Ten filter cubes were used to gather emission signal and then fast
      non-negative least squares regression (FNNLS) performed the unmixing process by
      assigning components of the 10-channel raw data to one of the five QDs used. the
      average error in the unmixing process was measured to be 7.60% when all filters
      were used and 7.80% when only 6 filters were used. 

PMID- 24110362
TI  - Automated annotation removal in agar plates.
AB  - Agar plates are widely used in the biomedical field as a medium in which to
      artificially grow bacteria, algae or fungi. Agar plates (Petri dishes) are used
      routinely in microbiology laboratories in order to identify the type of micro
      organism responsible for infections. Such diagnoses are based on counting the
      number and type of bacterial colonies growing in the Petri dish. The count of
      bacterial colonies is a time consuming task prone to human error, so interest in
      automated counting systems has increased in the recent years. One of the
      difficulties of automatizing the counting process is the presence of markers and
      annotations made in the lower part of the agar plate. Efficient removal of such
      markers can increase the accuracy of the bacterial counting system. This article
      introduces a fast method for detection, segmentation and removal of annotations
      in agar plates that improves the results of existing bacterial colony counting
      algorithms. 

PMID- 24110363
TI  - Dynamic illumination based system to remove the glare and improve the quality of
      medical images.
AB  - Medical images taken from camera based devices (e.g. laparoscope, colposcope,
      retinoscope, etc) are greatly affected by numerous bright reflection spots
      (called glare or specular reflections). This may affect the visibility of the
      abnormal features (if present in the glare locations). We have developed a novel
      solution to overcome this problem by incorporating a multi-LED lighting solution.
      This will intelligently and rapidly switch on and off the LED's in a pattern that
      dynamically and geometrically shifts/shuffles these glare spots back and forth in
      the image such that every glare-affected area of a single image frame can be
      reconstructed from a few adjacent time-frame images. We have built the prototype
      that successfully demonstrates how the glare problem in the medical video/image
      can be satisfactorily solved, significantly enhancing the accuracy of this vital
      procedure in the diagnosis of diseases. We achieve 65-95% reduction in
      specularity on phantom model using the proposed approach. 

PMID- 24110364
TI  - Variable incidence angle subwavelegth grating SPR graphene biosensor.
AB  - This paper investigates the sensitivity enhancement of a variable incidence angle
      subwavelength grating based multilayer surface plasmon resonance biosensor
      (SPRB). In the proposed design, a periodic array of subwavelength grating is
      integrated on top of a layer of graphene sheet in the multilayer SPR biosensor.
      The performance of the biosensor is investigated through monitoring the
      biomolecular interactions of cDNA-ssDNA interactions on its surface. The
      sensitivity improvement is indicated by the shift of the resonance peak angle. 

PMID- 24110365
TI  - Electrode placement in bioimpedance spectroscopy: evaluation of alternative
      positioning of electrodes when measuring relative dehydration in athletes.
AB  - In order to maintain a homeostatic environment in human cells, the balance
      between absorption and separation of water must be retained. Imbalance will have
      consequences on both the cellular and organ levels. Studies performed on athletes
      have shown coherence between their hydration status and ability to perform. A
      dehydration of 2-7% of total body weight resulted in a marked decrease in
      performance. Measurement and monitoring of hydration status may be used to
      optimize athlete performance. Therefore, in this current study bioimpedance
      spectroscopy is used to determine the hydration status of athletes. Trials were
      made to investigate alternative ways of electrode placement when performing
      bioimpedance spectroscopy in order to measure relative dehydration. A total of 14
      test subjects underwent measurements before, during, and after a cycle test of
      3*25min. Electrodes where placed to measure body impedance in three different
      ways: wrist-ankle (recommended method), wrist-wrist, and transthoracic.
      Furthermore, the relative loss in weight of the subjects during the trial was
      registered. The study showed no relation between relative weight loss and the
      wrist-wrist and transthoracic placement method, using bioimpedance spectroscopy
      to measure relative dehydration. The inability of the method to detect such
      relative changes in hydration may be due to the bioimpedance spectroscopy
      technology being extremely sensitive to changes in skin temperature, movement
      artifacts, thoroughness in placing the electrodes, and the physiological impact
      on the human body when performing exercise. Therefore, further research into the
      area of bioimpedance spectroscopy is needed before this methodology can be
      applied in monitoring active athletes. Hence, a simple weight measurement still
      seems a more useful way of determining a relative change of hydration in an
      active setting. 

PMID- 24110366
TI  - Investigation of the photoelectrochemical effect in optoelectrodes and potential
      uses for implantable electrode characterization.
AB  - The combination of optical stimulation and electrical recording is commonly
      employed in neuroscience research. Researchers using optogenetics are familiar
      with the photo-induced "artifacts" that arise from illumination of an electrode
      array. We sought to characterize this photoelectrochemical (PEC) effect to
      understand the underlying mechanism seen on NeuroNexus optoelectrodes. In doing
      so, we discovered that the phenomenon is inversely proportional to electrode site
      area in the same manner as electrical impedance measurements. We have applied the
      PEC effect as a method of electrode evaluation and show that a PEC measurement
      system can be both faster and more effective than impedance at sensing defects in
      high-throughput biomedical device testing. 

PMID- 24110367
TI  - Advanced fluorescence lifetime imaging algorithms for CMOS single-photon sensor
      based multi-focal multi-photon microscopy.
AB  - We have developed a fast hardware friendly bi-exponential fluorescence lifetime
      algorithm suitable for 2D CMOS single-photon avalanche diode (SPAD) arrays. The
      performance of the proposed algorithm against other techniques is demonstrated on
      the data from a plant specimen (Convallaria) by using 0.13um CMOS SPAD arrays
      mounted on a multi-beam multi-photon microscopy system. 

PMID- 24110368
TI  - Fluorescence-based method for assessment of blood-brain barrier disruption.
AB  - We report on a fluorescence-based optical method for assessment of blood-brain
      barrier in humans. The technique is based on monitoring of fluorescence light
      excited in the dye circulating in the brain. Measurements were carried out in
      healthy volunteers and in patients with disruption of the blood-brain barrier
      with the use of time-resolved method during inflow and washout of indocyanine
      green after its intravenous injection. We show large differences in the
      fluorescence signals - in healthy subjects a fast washout of the dye can be
      observed whereas in patients the washout is significantly prolonged. We conclude
      that the monitoring of the fluorescence signals during injection of exogenous
      optical contrast agent can be used for the assessment of the condition of blood
      brain barrier at the bedside. The technique may be of benefit for diagnosis of
      the patients suffering from damage of the blood-brain barrier and in monitoring
      of therapies used in such patients. 

PMID- 24110369
TI  - Design of organic scintillators for non-standard radiation field dosimetry:
      experimental setup.
AB  - This paper describes an experimental setup designed for sensing the luminescent
      light coming from an organic plastic scintillator stimulated with ionizing
      radiation. This device is intended to be a part of a complete dosimeter system
      for characterization of small radiation fields which is the project of the
      doctoral thesis of the medical physicist at the Radiation Oncology facility of
      Hospital San Vicente Fundacion in conjunction with the Universidad de Antioquia
      of Medellin Colombia. Some preliminary results predict a good performance of the
      unit, but further studies must be conducted in order to have a completed
      evaluation of the system. This is the first step in the development of an
      accuracy tool for measurement of non-standard fields in the Radiotherapy or
      Radiosurgery processes. 

PMID- 24110370
TI  - Directional dual-tree complex wavelet packet transform.
AB  - Doppler ultrasound systems, which are widely used in cardiovascular disorders
      detection, have quadrature format outputs. Various types of algorithms were
      described in literature to process quadrature Doppler signals (QDS), such as
      phasing filter technique (PFT), fast Fourier transform method, frequency domain
      Hilbert transform method and complex continuous wavelet transform. However for
      the discrete wavelet transform (DWT) case, which becomes a common method for
      processing QDSs, there was not a direct method to recover flow direction from
      quadrature signals. Traditionally, to process QDSs with DWT, firstly directional
      signals have to be extracted and later two DWTs must be applied. Although there
      exists a complex DWT algorithm called dual tree complex discrete wavelet
      transform (DTCWT), it does not provide directional signal decoding during
      analysis because of the unwanted energy leaks into its negative frequency bands.
      Modified DTCWT, which is a combination of PFT and DTCWT, has the capability of
      extracting directional information while decomposing QDSs into different
      frequency bands, but it uses an additional Hilbert transform filter and it
      increases the computational complexity of whole transform. Discrete wavelet
      packet transform (DWPT), which is a generalization of the ordinary DWT allowing
      subband analysis without the constraint of dyadic decomposition, can perform an
      adaptive decomposition of the frequency axis. In this study, a novel complex
      DWPT, which maps directional information while processing QDSs, is proposed. The
      success of proposed method will be measured by using simulated quadrature
      signals. 

PMID- 24110371
TI  - Embolic Doppler ultrasound signal detection via fractional Fourier transform.
AB  - Computerized analysis of Doppler ultrasound signals can aid early detection of
      asymptomatic circulating emboli. For analysis, physicians use informative
      features extracted from Doppler ultrasound signals. Time -frequency analysis
      methods are useful tools to exploit the transient like signals such as Embolic
      signals. Detection of discriminative features would be the first step toward
      automated analysis of embolic Doppler ultrasound signals. The most problematic
      part of setting up emboli detection system is to differentiate embolic signals
      from confusing similar wave-like patterns such as Doppler speckle and artifacts
      caused by tissue movement, probe tapping, speaking etc. In this study, discrete
      version of fractional Fourier transform is presented as a solution in the
      detection of emboli in digitized Doppler ultrasound signals. An accurate set of
      parameters are extracted using short time Fourier transform and fractional
      Fourier transform and the results are compared to reveal detection quality.
      Experimental results prove the efficiency of fractional Fourier transform in
      which discriminative features becomes more evident. 

PMID- 24110372
TI  - Comparison of robustness against missing values of alternative decision tree and
      multiple logistic regression for predicting clinical data in primary breast
      cancer.
AB  - Nomogram based on multiple logistic regression (MLR) is a standard technique for
      predicting diagnostic and treatment outcomes in medical fields. However, the
      applicability of MLR to data mining of clinical information is limited. To
      overcome these issues, we have developed prediction models using ensembles of
      alternative decision trees (ADTree). Here, we compare the performance of MLR and
      ADTree models in terms of robustness against missing values. As a case study, we
      employ datasets including pathological complete response (pCR) of neoadjuvant
      therapy, one of the most important decision-making factors in the diagnosis and
      treatment of primary breast cancer. Ensembled ADTree models are more robust
      against missing values than MLR. Sufficient robustness is attained at low
      boosting and ensemble number, and is compromised as these numbers increase. 

PMID- 24110373
TI  - Reconfiguration-based implementation of SVM classifier on FPGA for Classifying
      Microarray data.
AB  - Classifying Microarray data, which are of high dimensional nature, requires high
      computational power. Support Vector Machines-based classifier (SVM) is among the
      most common and successful classifiers used in the analysis of Microarray data
      but also requires high computational power due to its complex mathematical
      architecture. Implementing SVM on hardware exploits the parallelism available
      within the algorithm kernels to accelerate the classification of Microarray data.
      In this work, a flexible, dynamically and partially reconfigurable implementation
      of the SVM classifier on Field Programmable Gate Array (FPGA) is presented. The
      SVM architecture achieved up to 85* speed-up over equivalent general purpose
      processor (GPP) showing the capability of FPGAs in enhancing the performance of
      SVM-based analysis of Microarray data as well as future bioinformatics
      applications. 

PMID- 24110374
TI  - Comparison of aggregators for multi-objective SNP selection.
AB  - SNPs (Single Nucleotide Polymorphisms) are genomic variants that associate with
      many genetic characteristics. These variants can also be utilized to track the on
      going mutation in population genetics. The goal of this study was to select the
      most relevant SNP subsets for discriminating ethnic groups. Each SNP was
      evaluated by its: i) Mutual information, ii) Relief-F score, iii) Loadings of the
      first principal component, iv) Loadings of the second principal component.
      Combining these four feature ranking criteria in different ways, three different
      aggregation methods (Pareto Optimal, Condorcet, MC4) were compared with respect
      to their SNP selection accuracies. Results showed that SNP subsets chosen with
      Pareto Optimal yielded better classification accuracy. 

PMID- 24110375
TI  - Signal-processing-based bioinformatics approach for the identification of
      influenza A virus subtypes in neuraminidase genes.
AB  - Neuraminidase (NA) genes of influenza A virus is a highly potential candidate for
      antiviral drug development that can only be realized through true identification
      of its sub-types. In this paper, in order to accurately detect the sub-types, a
      hybrid predictive model is therefore developed and tested over proteins obtained
      from the four subtypes of the influenza A virus, namely, H1N1, H2N2, H3N2 and
      H5N1 that caused major pandemics in the twentieth century. The predictive model
      is built by the following four main steps; (i) decoding the protein sequences
      into numerical signals by means of EIIP amino acid scale, (ii) analysing these
      signals (protein sequences) by using Discrete Fourier Transform (DFT) and
      extracting DFT-based features, (iii) selecting more influential sub-set of the
      features by using the F-score statistical feature selection method, and finally
      (iv) building a predictive model on the feature sub-set by using support vector
      machine classifier. The protein sequences were chosen as to be of high percentage
      identity that they demonstrate within individual influenza subtype classes and
      high variation that they display in the percentage identity. This makes the
      proteins very difficult to distinguish from each other even they belong to
      different subtypes. Given this set of the proteins, the predictive model yielded
      98.3% accuracy based on a 5-fold cross validation. This also results in a twenty
      feature sub-set that can also help reveal spectral characteristics of the
      subtypes. The proposed model is promising and can easily be generalized for other
      similar studies. 

PMID- 24110376
TI  - Effect of vibrotactile feedback on an EMG-based proportional cursor control
      system.
AB  - Surface electromyography (sEMG) has been introduced into the bio-mechatronics
      systems, however, most of them are lack of the sensory feedback. In this paper,
      the effect of vibrotactile feedback for a myoelectric cursor control system is
      investigated quantitatively. Simultaneous and proportional control signals are
      extracted from EMG using a muscle synergy model. Different types of feedback
      including vibrotactile feedback and visual feedback are added, assessed and
      compared with each other. The results show that vibrotactile feedback is capable
      of improving the performance of EMG-based human machine interface. 

PMID- 24110377
TI  - Neuromechanical sensor fusion yields highest accuracies in predicting ambulation
      mode transitions for trans-tibial amputees.
AB  - Advances in battery and actuator technology have enabled clinical use of powered
      lower limb prostheses such as the BiOM Powered Ankle. To allow ambulation over
      various types of terrains, such devices rely on built-in mechanical sensors or
      manual actuation by the amputee to transition into an operational mode that is
      suitable for a given terrain. It is unclear if mechanical sensors alone can
      accurately modulate operational modes while voluntary actuation prevents
      seamless, naturalistic gait. Ensuring that the prosthesis is ready to accommodate
      new terrain types at first step is critical for user safety. EMG signals from
      patient's residual leg muscles may provide additional information to accurately
      choose the proper mode of prosthesis operation. Using a pattern recognition
      classifier we compared the accuracy of predicting 8 different mode transitions
      based on (1) prosthesis mechanical sensor output (2) EMG recorded from residual
      limb and (3) fusion of EMG and mechanical sensor data. Our findings indicate that
      the neuromechanical sensor fusion significantly decreases errors in predicting 10
      mode transitions as compared to using either mechanical sensors or EMG alone
      (2.3+/-0.7% vs. 7.8+/-0.9% and 20.2+/-2.0% respectively). 

PMID- 24110378
TI  - Design and analysis of an antenna for wireless energy harvesting in a head
      mountable DBS device.
AB  - This paper presents design and simulation of a circular meander dipole antenna at
      the industrial, scientific, and medical band of 915 MHz for energy scavenging in
      a passive head-mountable deep brain stimulation device. The interaction of the
      proposed antenna with a rat body is modeled and discussed. In the antenna, the
      radiating layer is meandered, and a FR-4 substrate is used to limit the radius
      and height of the antenna to 14 mm and 1.60 mm, respectively. The resonance
      frequency of the designed antenna is 915 MHz and the bandwidth of 15 MHz at a
      return loss of -10 dB in free space. To model the interaction of the antenna with
      a rat body, two aspects including functional and biological are considered. The
      functional aspect includes input impedance, resonance frequency, gain pattern,
      radiation efficiency of the antenna, and the biological aspect involves electric
      field distribution, and SAR value. A complete rat model is used in the finite
      difference time domain based EM simulation software XFdtd. The simulated results
      demonstrate that the specific absorption rate distributions occur within the
      skull in the rat model, and their values are higher than the standard regulated
      values for the antenna receiving power of 1W. 

PMID- 24110379
TI  - Electric field characteristics of electroconvulsive therapy with individualized
      current amplitude: a preclinical study.
AB  - This study examines the characteristics of the electric field induced in the
      brain by electroconvulsive therapy (ECT) with individualized current amplitude.
      The electric field induced by bilateral (BL), bifrontal (BF), right unilateral
      (RUL), and frontomedial (FM) ECT electrode configurations was computed in
      anatomically realistic finite element models of four nonhuman primates (NHPs). We
      generated maps of the electric field strength relative to an empirical neural
      activation threshold, and determined the stimulation strength and focality at
      fixed current amplitude and at individualized current amplitudes corresponding to
      seizure threshold (ST) measured in the anesthetized NHPs. The results show less
      variation in brain volume stimulated above threshold with individualized current
      amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the
      stimulated brain volume at amplitude-titrated ST is substantially lower than that
      for ECT with conventional fixed current amplitudes. Thus individualizing the ECT
      stimulus current could compensate for individual anatomical variability and
      result in more focal and uniform electric field exposure across different
      subjects compared to the standard clinical practice of using high, fixed current
      for all patients. 

PMID- 24110380
TI  - An electroacoustic recording device for wireless sensing of neural signals.
AB  - Elimination of wires connecting neural recording electrodes to external
      electronics is highly desired, particularly in survival animal studies, due to
      neural damage and the device failures caused by these wires. In this study, an
      electroacoustic device for sensing and wireless transmission of neural signals to
      an external unit is proposed and results from a prototype are presented. In this
      method, the neural signals modulate the acoustic pulse amplitudes generated by a
      small piezoelectric element that is implanted at the recording site. The
      acoustics waves are detected wirelessly outside the nervous system by another
      piezoelectric transducer and the neural signals are extracted by amplitude
      demodulation. To test the prototype, a sinusoidal signal with 100uVpp amplitude
      was applied in phosphate buffered saline to simulated neural signals and the
      external transducer was placed 10mm away from the recording element. The results
      show that a sinusoidal signal of the given amplitude could be wirelessly sensed
      and reconstructed with a signal-to-noise ratio of 14dB. 

PMID- 24110381
TI  - ERP component analysis for rapid image searching in finer categories.
AB  - Event-related potentials (ERP)-based image triage (or search) in the context of
      Rapid Serial Visual Presentation (RSVP) exploits difference in the human brain
      response to target and distracted stimuli in the form of an image. So far, most
      paradigms focus on image triage (or search) among rough object categories. In
      this paper, we explored the possibility and effectiveness of target detection
      among finer categories like different animals. We analyzed on the difference of
      ERP components in two image search tasks, a simple-recognition task in which all
      images of a target are the same and a discriminative-recognition task in which
      all images are randomly different but belong to the same target category (the
      same kind of animal). We observed that the P3 amplitude reduced and the P3
      latency delayed on the discriminative-recognition condition due to the increased
      difficulty of identifying different images belonging to the same category. But
      the average area under ROC curve reached 0.82 which indicated that rapid target
      detection among finer categories by single-trial ERP were feasible with trivial
      contribution of N1 and stable contribution of N2 and P3. 

PMID- 24110382
TI  - Freeing the visual channel by exploiting vibrotactile BCI feedback.
AB  - Controlling a brain-actuated device requires the participant to look at and to
      split his attention between the interaction of the device with its environment
      and the status information of the Brain-Computer Interface (BCI). Such parallel
      visual tasks are partly contradictory, with the goal of achieving a good and
      natural device control. Is there a possibility to free the visual channel from
      one of these tasks? To address this, a stimulation system based on 6 coin-motors
      is developed, which provides a spatially continuous tactile illusion as BCI
      feedback, so that the visual channel can be devoted to the device. Several
      experiments are conducted in this work, to optimize the tactile illusion patterns
      and to investigate the influence on the electroencephalogram (EEG). Finally, 6
      healthy BCI participants compare visual with tactile feedback in online BCI
      recordings. The developed stimulator can be used without interfering with the
      EEG. All subjects are able to perceive this type of tactile feedback well, and no
      statistical degradation in the online BCI performance could be identified between
      visual and tactile feedback. 

PMID- 24110383
TI  - A hybrid BCI for enhanced control of a telepresence robot.
AB  - Motor-disabled end users have successfully driven a telepresence robot in a
      complex environment using a Brain-Computer Interface (BCI). However, to
      facilitate the interaction aspect that underpins the notion of telepresence,
      users must be able to voluntarily and reliably stop the robot at any moment, not
      just drive from point to point. In this work, we propose to exploit the user's
      residual muscular activity to provide a fast and reliable control channel, which
      can start/stop the telepresence robot at any moment. Our preliminary results show
      that not only does this hybrid approach increase the accuracy, but it also helps
      to reduce the workload and was the preferred control paradigm of all the
      participants. 

PMID- 24110384
TI  - A mental switch-based asynchronous brain-computer interface for 2D cursor
      control.
AB  - In the present study, we developed a mental switch-based asynchronous brain
      computer interface for 2D cursor control. Two mental switches were designed: one
      was to switch from non-intentional to intentional control state, and the other
      one for conducting the reverse process. 2D control and mental switches are all
      based on three-class motor imagery. With four subjects participating in the
      study, the experimental results demonstrated the efficiency of the proposed
      asynchronous 2D control strategy. 

PMID- 24110385
TI  - Effect of posterized naturalistic stimuli on SSVEP-based BCI.
AB  - Most visual stimuli used in steady-state visual evoked potential (SSVEP)-based
      brain-computer interface (BCI) are simple and elementary. Examples of such
      stimuli are checkerboard patterns and sinusoidal gratings. These stimuli exhibit
      distinct contrasts and edges that conform well to the simple cortical cells
      behavior first observed by Hubel and Weisel. Hence, they are effective in
      eliciting VEP. On the other hand, the use of naturalistic stimuli is known to
      advance our understanding of early visual system. However, naturalistic stimuli
      are spectrally and spatially complex. They may not elicit the optimal VEP and the
      results obtained may not easily correlate to the stimulus parameters. Hence, we
      proposed to posterize natural images to generate naturalistic stimuli suitable
      for SSVEP-BCI. The posterization process considers both the edge and contrast
      information of the input image. This study elucidates the effect of posterized
      naturalistic stimuli on SSVEP amplitudes and phases by exploring the relationship
      between the number of tones of posterized visual stimuli and their effect on the
      power spectra and phase synchrony of attended stimuli. Results show that
      posterized visual stimuli at four tone display a significant effect on the
      dominant frequency response. Our findings suggest the effectiveness of posterized
      naturalistic stimuli and should advance the use of naturalistic stimuli in SSVEP
      BCI. 

PMID- 24110386
TI  - An externally head-mounted wireless neural recording device for laboratory animal
      research and possible human clinical use.
AB  - In this paper we present a new type of head-mounted wireless neural recording
      device in a highly compact package, dedicated for untethered laboratory animal
      research and designed for future mobile human clinical use. The device, which
      takes its input from an array of intracortical microelectrode arrays (MEA) has
      ninety-seven broadband parallel neural recording channels and was integrated on
      to two custom designed printed circuit boards. These house several low power,
      custom integrated circuits, including a preamplifier ASIC, a controller ASIC,
      plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester
      encoder. Another ultralow power RF chip supports an OOK transmitter with the
      center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss
      dielectric board together with a 3V LDO, with output fed to a UWB chip antenna.
      The IC boards were interconnected and packaged in a polyether ether ketone (PEEK)
      enclosure which is compatible with both animal and human use (e.g. sterilizable).
      The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which
      operates the device for more than 2 days. The overall system includes a custom RF
      receiver electronics which are designed to directly interface with any number of
      commercial (or custom) neural signal processors for multi-channel broadband
      neural recording. Bench-top measurements and in vivo testing of the device in
      rhesus macaques are presented to demonstrate the performance of the wireless
      neural interface. 

PMID- 24110387
TI  - Constant RMS versus constant peak modulation for the perceptual equivalence of
      sinusoidal amplitude modulated signals.
AB  - Neuroprosthetics using intracortical microstimulation can potentially alleviate
      sensory deprivation due to injury or disease. However the information bandwidth
      of a single microstimulation channel remains largely unanswered. This paper
      presents three experiments that examine the importance of Peak Power/Charge and
      RMS Power/Charge for detection of acoustic and electrical Sinusoidal Amplitude
      Modulated stimuli by the auditory system. While the peripheral auditory system is
      sensitive to RMS power cues for the detection of acoustic stimuli, here we
      provide results that suggest that the auditory cortex is sensitive to peak charge
      cues for electrical stimuli. Varying the modulation frequency and depth do not
      change this effect for detection of modulated electrical stimuli. 

PMID- 24110388
TI  - Feasibility of 2nd generation STS retinal prosthesis in dogs.
AB  - We developed a 2(nd) generation suprachoroidal transretinal stimulation (STS)
      system with a 49 channel electrode array and implanted in 2 dogs. One month after
      surgery, all electrodes were functioning and the ocular fundus was normal in both
      dogs. The results indicate the 2(nd) generation STS retinal prosthesis is
      feasible and can be considered for clinical use. 

PMID- 24110389
TI  - A new concept for noninvasive tinnitus treatment utilizing multimodal pathways.
AB  - Current noninvasive treatments for tinnitus have shown mixed results. There have
      been encouraging developments in using invasive brain or vagal nerve stimulation
      to modulate neural populations driving the tinnitus percept. However, these
      invasive treatments can only be used in a small patient population with severe
      conditions. In this preliminary study, we present a new treatment option we call
      Multimodal Synchronization Therapy (MST), which attempts to achieve synchronized
      and localized brain activation without invasive neural stimulation. MST combines
      multiple sensory, motor, limbic, and cognitive inputs to elicit activation of
      multimodal neurons to potentially modulate specific neurons driving the tinnitus
      percept. We present preliminary data in a guinea pig model showing activation of
      somatosensory and auditory pathways to alter neural activity within the inferior
      colliculus, a multimodal integration region that has shown pathological changes
      in animals and patients with tinnitus. Electrical stimulation of different body
      locations induced excitatory responses in the inferior colliculus, eliciting
      responses in up to 41% of all recording sites for a given somatic site. Paired
      somatic and acoustic stimulation resulted in enhanced or suppressed acoustic
      driven neural activity in the inferior colliculus that varied depending on
      stimulation and recording location. Similar modulation effects were observed in
      the auditory cortex, which may relate to changes in auditory perception. Further
      studies need to incorporate multiple multimodal pathways and must also confirm
      that MST can suppress the abnormal neural patterns that directly drive the
      tinnitus percept. 

PMID- 24110390
TI  - Safe direct current stimulator 2: concept and design.
AB  - Essentially all neuroprostheses use alternating biphasic current pulses to
      stimulate neural tissue. While this method can effectively excite neurons, it is
      not very effective for inhibiting them. In contrast, direct current (DC) can
      excite, inhibit, and modulate sensitivity of neurons. However, DC stimulation is
      biologically unsafe because it violates safe charge injection criteria. We have
      previously described the concept of a safe direct current stimulator (SDCS) that
      overcomes this constraint. The SDCS drives DC ionic current into the tissue by
      switching fluid valves in phase with biphasic current pulses delivered to the
      metal electrodes within the device. The original prototype of this device, SDCS1,
      could both suppress and excite the vestibular nerve with DC stimulation delivered
      by the device. In the process of building the SDCS1 we identified several
      problems that must be addressed to further develop this technology. Consequently,
      we designed the SDCS2, which eliminates periodic interruptions in stimulation
      current flow observed in the original SDCS1 design and is small enough for head
      mounted use in chronic animal studies. 

PMID- 24110391
TI  - An artificial arm/hand system with a haptic sensory function using electric
      stimulation of peripheral sensory nerve fibers.
AB  - We are currently developing an artificial arm/hand system which is capable of
      sensing stimuli and then transferring these stimuli to users as somatic
      sensations. Presently, we are evoking the virtual somatic sensations by
      electrically stimulating a sensory nerve fiber which innervates a single
      mechanoreceptor unit at the target area; this is done using a tungsten
      microelectrode that was percutaneously inserted into the use's peripheral nerve
      (a microstimulation method). The artificial arm/hand system is composed of a
      robot hand equipped with a pressure sensor system on its fingers. The sensor
      system detects mechanical stimuli, which are transferred to the user by means of
      the microstimulation method so that the user experiences the stimuli as the
      corresponding somatic sensations. In trials, the system worked satisfactorily and
      there was a good correlation between the pressure applied to the pressure sensors
      on the robot fingers and the subjective intensities of the evoked pressure
      sensations. 

PMID- 24110392
TI  - Development of a chemical retinal prosthesis: stimulation of rat retina with
      glutamate.
AB  - Retinal degenerative diseases cause partial or total blindness and affect
      millions of people worldwide, yet currently have no treatment. Retinal prostheses
      using electrical stimulation are being developed but face significant problems
      moving forward. Here we propose using chemical stimulation, via the
      neurotransmitter glutamate, to modulate retinal ganglion cell (RGC) spike rates.
      Our results demonstrate that it is feasible to stimulate RGCs in an explanted
      retina using focal ejections of glutamate from either subretinal or epiretinal
      sides. Preliminary evidence suggests we are primarily activating RGCs as opposed
      to bipolar cells. This is an important first step in the development of a
      chemical retinal prosthesis based on microelectromechanical systems (MEMS)
      technology. 

PMID- 24110393
TI  - Manpower development for the biomedical industry space.
AB  - The Biomedical Sciences (BMS) Cluster is one of four key pillars of the Singapore
      economy. The Singapore Government has injected research funding for basic and
      translational research to attract companies to carry out their commercial R&D
      activities. To further intensify the R&D efforts, the National Research
      Foundation (NRF) was set up to coordinate the research activities of different
      agencies within the larger national framework and to fund strategic R&D
      initiatives. In recent years, funding agencies began to focus on support of
      translational and clinical research, particularly those with potential for
      commercialization. Translational research is beginning to have traction, in
      particular research funding for the development of innovation medical devices.
      Therefore, the Biomedical Sciences sector is projected to grow which means that
      there is a need to invest in human capital development to achieve sustainable
      growth. In support of this, education and training programs to strengthen the
      manpower capabilities for the Biomedical Sciences industry have been developed.
      In recent years, undergraduate and graduate degree courses in biomedical
      engineering/bioengineering have been developing at a rapid rate. The goal is to
      train students with skills to understand complex issues of biomedicine and to
      develop and implement of advanced technological applications to these problems.
      There are a variety of career opportunities open to graduates in biomedical
      engineering, however regardless of the type of career choices, students must not
      only focus on achieving good grades. They have to develop their marketability to
      employers through internships, overseas exchange programs, and involvement in
      leadership-type activities. Furthermore, curriculum has to be developed with
      biomedical innovation in mind and ensure relevance to the industry. The objective
      of this paper is to present the NUS Bioengineering undergraduate program in
      relation to manpower development for the biomedical industry in Singapore. 

PMID- 24110394
TI  - Promoting interdisciplinary project-based learning to build the skill sets for
      research and development of medical devices in academia.
AB  - The worldwide need for rapid expansion and diversification of medical devices and
      the corresponding requirements in industry pose arduous challenges for educators
      to train undergraduate biomedical engineering (BME) students. Preparing BME
      students for working in the research and development (R&D) in medical device
      industry is not easily accomplished by adopting traditional pedagogical methods.
      Even with the inclusion of the design and development elements in capstone
      projects, medical device industry may be still experience a gap in fulfilling
      their needs in R&D. This paper proposes a new model based on interdisciplinary
      project-based learning (IDPBL) to address the requirements of building the
      necessary skill sets in academia for carrying out R&D in medical device industry.
      The proposed model incorporates IDPBL modules distributed in a stepwise fashion
      through the four years of a typical BME program. The proposed model involves buy
      in and collaboration from faculty as well as students. The implementation of the
      proposed design in an undergraduate BME program is still in process. However, a
      variant of the proposed IDPBL method has been attempted at a limited scale at the
      postgraduate level and has shown some success. Extrapolating the previous
      results, the adoption of the IDPBL to BME training seems to suggest promising
      outcomes. Despite numerous implementation challenges, with continued efforts, the
      proposed IDPBL will be valuable n academia for skill sets building for medical
      device R&D. 

PMID- 24110395
TI  - Managing new directions for a 38 year old undergraduate BME program.
AB  - The Biomedical Engineering curricula in general must reflect the state of the art
      in the technology related to medicine and health care, as students who graduate
      from these programs are directly related to the well-being of the patients,
      either through new devices and technologies being invented or through the
      application of their technical knowledge in the service industry. At present,
      there are more than 25 BME undergraduate programs in Mexico. Most of them are
      oriented towards the instrumentation and clinical engineering branches of the
      field, while a few others have strong components in signal analysis. The program
      at Universidad Autonoma Metropolitana (UAM) is one of the oldest and has been
      used as a reference by most other programs. Since UAM is one of the top three
      research universities in the country, it is well poised to incorporate its
      research directions into a more modern curriculum. This paper deals with the
      efforts that have been carried out in order to minimize the excessive influence
      of the electrical engineering subjects in the BME undergraduate curriculum and
      the approaches to reach consensus-based decisions to explore new directions
      related to emerging disciplines in medical technology and health care. After
      analysis of the current state, a discussion on future directions is presented. 

PMID- 24110396
TI  - A hands-on course teaching bioinstrumentation through the design and construction
      of a benchtop cardiac pacemaker.
AB  - We have developed a bioinstrumentation course that emphasizes practical
      application of engineering and biological concepts by having students focus on
      the development of a single biomedical device: a cardiac pacemaker. In creating
      their benchtop pacemaker, students learn about and design sensing circuitry, data
      acquisition and processing code, control system algorithms, and stimulation
      electronics. They also gain an understanding of cardiac anatomy and
      electrophysiology. The separate elements of the pacemaker created throughout the
      semester will be repeatedly tested, re-designed, and integrated with one another,
      culminating in an emulated pacemaker whose efficacy will be tested on North
      American bullfrogs. It is hypothesized that the hands-on learning in this course,
      coupled with the practical application of concepts in the context of a single
      biomedical device, will enhance students' skills in bioinstrumentation design. 

PMID- 24110397
TI  - Education and training in regulatory science for medical device development.
AB  - Regulatory science can be defined as the science aimed at the optimal
      introduction into society of new products of science, such as discovered
      substances and new scientific tools and technologies as well as knowledge and
      information. In addition to engineering researches that create novel medical
      devices, scientific methods for evaluating efficacy, safety and quality of
      medical devices are necessary to enable rational and scientific evaluation of the
      device in device approval process. Engineers and medical doctors involving
      research and development of novel medical devices are required to have basic
      knowledge on medical device safety standard, medical device regulation, and
      relevant methodologies. In Japan, several graduate schools in Japan have started
      educational programs on regulatory sciences in collaboration of Pharmaceuticals
      and Medical Devices Agency (PMDA), Japan. In 2012, program for researches for
      development of evaluation guidelines for novel medical device products started
      where personnel exchanges between academic researches institutes and PMDA.
      Example of these programs will be introduced in the presentation and its impact
      on improvement of medical device research and development process will be
      discussed. 

PMID- 24110398
TI  - Model for assessing aesthetic devices based on interdisciplinary work among the
      government, academy and industry.
AB  - In Colombia, just the same as in the whole World, globalization of the market led
      to a large increase in importating of diverse devices. In case of devices for
      aesthetic use, importing a large number of different device types without
      adequate control of products, increases the risk of appearance of adverse events
      for their users. On the other hand, there are very few studies of adverse events
      caused by their use, or risk assessment studies. This paper presents the role of
      academy in defining the conditions for safety of aesthetic devices and evaluation
      of medical devices "Class 1", for use in aesthetics. With support of the
      Colombian government, the Pan American Health Organization PAHO, and the
      regulating entity INVIMA, we proposed a model of control and regulation of use of
      devices for aesthetics in order to achieve ease of classification and ensure
      adequate use of devices for aesthetics, and to minimize the risk for users of the
      technology. As a result of this model, a tool was developed to facilitate to the
      regulatory entity the classification and evaluation of devices for aesthetic use
      "Class 1", which will be implemented by the Colombian government with the support
      of biomedical engineers having the required knowledge and skills. 

PMID- 24110399
TI  - Robotic thumb grasp-based range of motion optimisation.
AB  - With the thumb serving an important role in the function of the human hand,
      improving robotic prosthetic thumb functionality will have a direct impact on the
      prosthesis itself. So far, no significant work exists that examines the ranges of
      motion a prosthetic thumb should exhibit; many myoelectric prostheses arbitrarily
      select them. We question this design practice as we expect a significant
      functional volume reduction for performing certain activities vs. the maximum
      obtainable workspace. To this end, we compare and contrast four anatomically
      accurate thumb models. We quantify their angular ranges of motion by generating
      point clouds of end-effector positions, and by computing their alpha-shape
      bounded volumes. Examining the function of the thumb for several grasps, we
      identify a 76% reduction of the required workspace volume vis-a-vis the maximum
      volume of a "'generic'" human thumb. 

PMID- 24110400
TI  - Biomechanical effects of screw fixation in second mandibular reconstruction
      plate.
AB  - The purpose of this study was to investigate biomechanical effects of second
      reconstruction plate with different combinations of fixed screws in patient with
      mandibular tumor resection by three-dimensional finite element analysis (FEA).
      The FEA models were consisted of defected mandible, reconstruction plate with
      different screw holes, and bone screws. The results indicated that application of
      the second reconstruction plate appeared to increase stability and decrease
      stress magnitude on the plates and screws accompanying with increasing screw
      number. For clinical cost consideration in usage of the second reconstruction
      plate, the conclusion showed that the second reconstruction plate could offer a
      better mechanical efficacy accompanying with increase of screw quantity, but
      single screw applied for the second plate fixation to defected mandible of tumor
      resection was enough to stabilize without increase of screw quantities. 

PMID- 24110401
TI  - Investigation of repeatability in hip fracture risk predicted by DXA-based finite
      element model.
AB  - DXA (dual energy X-ray absorptiometry) based finite element model is able to
      integrate all mechanical factors affecting hip fracture in osteoporosis patients
      and it is thus, in principle, more reliable than areal bone mineral density (BMD)
      for assessing fracture risk. However, short-term repeatability of DXA-based
      finite element model in predicting fracture risk has not yet been investigated
      and satisfactory repeatability is a prerequisite for the procedure to be applied
      in clinic. Therefore, in the reported research, the repeatability of a previously
      developed DXA-based patient-specific finite element procedure was investigated.
      It was found that inconsistence in positioning the patient during DXA scanning
      and manual segmentation of DXA image in constructing the finite element model are
      the two dominant factors affecting short-term repeatability of the finite element
      procedure. The study outcome indicated that to apply the finite element procedure
      in clinic, a set of more strict guidelines for positioning the patient in DXA
      scanning must be established and followed. 

PMID- 24110403
TI  - The effect of foot compliance encoded in the windlass mechanism on the energetics
      of human walking.
AB  - The human foot, which is the part of the body that interacts with the environment
      during locomotion, consists of rich biomechanical design. One of the unique
      designs of human feet is the windlass mechanism. In a previous simulation study,
      we found that the windlass mechanism seems to improve the energy efficiency of
      walking. To better understand the origin of this efficiency, we here conduct both
      simulation and experimental studies exploring the influence of foot compliance,
      which is one of the functionalities that the windlass mechanism embeds, on the
      energetics of walking. The studies show that walking with compliant feet incurs
      more energetic costs than walking with stiff feet. The preliminary results
      suggest that the energy saved by introducing the windlass mechanism does not
      originate from the compliance it embeds. We speculate that the energy savings of
      the windlass mechanism are related more to its contribution to reducing the
      effective foot length in swing than to providing compliance in stance. 

PMID- 24110404
TI  - Biomechanical evaluation of an orthodontic mini-implant with plastic removal cap:
      an in-vitro experimental testing.
AB  - This study evaluates the biomechanical interactions of a mini-implant using a
      plastic revolving cap (PRC) with translation/rotation features for optional
      orthodontic traction. An orthodontic mini-implant and the PRC consisting of a
      hexagon connection onto mini-implant with 60 degree switching unit and an
      extended arm to provide orthodontic wire tied at different positions. The PRC
      removal force was measured by pull-out testing. The PRC removal force remained
      larger than three times the finger pulling force (9.3N) after 5 repeated removal
      tests. The results for the PRC resistant testing showed that the PRC rotational
      resistant force (20.31+/-0.83N) is larger than the maximum traction force (about
      4.9N) for orthodontic treatment. The mini-implant used with PRC can provide
      translation and rotation features to change the angles and directions of
      orthodontic tractions for most effective anchorage preparation under safety
      consideration. 

PMID- 24110405
TI  - Saccadic Vector Optokinetic Perimetry (SVOP): a novel technique for automated
      static perimetry in children using eye tracking.
AB  - Perimetry is essential for identifying visual field defects due to disorders of
      the eye and brain. However, young children are often unable to reliably perform
      the preferred method of visual field assessment known as automated static
      perimetry (ASP). This paper introduces a novel method of ASP specifically
      developed for children called Saccadic Vector Optokinetic Perimetry (SVOP). SVOP
      uses eye tracking to detect the natural saccadic eye response of gaze orientation
      towards visual field stimuli if they are seen. In this paper, the direction and
      magnitude of a sample of subject gaze responses to visual field stimuli is used
      to construct a software decision algorithm for use in SVOP. SVOP was clinically
      evaluated in a group of 24 subjects, comprising children and adults, with and
      without visual field defects, by comparison with an equivalent test on the
      Humphrey Field Analyser (HFA). SVOP provides promising visual field test results
      when compared with the reference HFA test, and has proven extremely useful in
      detecting visual field defects in children unable to perform traditional ASP. 

PMID- 24110406
TI  - Intraocular electro-optic lens with ciliary muscle controlled accommodation.
AB  - In this paper a concept is proposed of an intraocular lens implant with electro
      optic accommodation of a variable-focus hybrid liquid-crystal-based lens. The
      dioptric strength of the lens is electronically controlled by a signal that is
      derived from the change of inductance of a sensing coil due to a marker implanted
      in the nearby contracting or decontracting ciliary muscle. Analytical, numerical
      and experimental results are reported on the dependency of the frequency of a
      Colpitts oscillator circuit on the location of a nearby conductive marker. A
      concept is also reported on the use as an electro-optic lens of a device based on
      a liquid crystal in planar alignment, which is held between a flat and a curved
      window coated with optically transparent and electrically conductive layers. 

PMID- 24110407
TI  - 3D gaze tracking system for NVidia 3D Vision(r).
AB  - Inappropriate parallax setting in stereoscopic content generally causes visual
      fatigue and visual discomfort. To optimize three dimensional (3D) effects in
      stereoscopic content by taking into account health issue, understanding how user
      gazes at 3D direction in virtual space is currently an important research topic.
      In this paper, we report the study of developing a novel 3D gaze tracking system
      for Nvidia 3D Vision((r)) to be used in desktop stereoscopic display. We suggest
      an optimized geometric method to accurately measure the position of virtual 3D
      object. Our experimental result shows that the proposed system achieved better
      accuracy compared to conventional geometric method by average errors 0.83 cm,
      0.87 cm, and 1.06 cm in X, Y, and Z dimensions, respectively. 

PMID- 24110408
TI  - Rollable and implantable intraocular pressure sensor for the continuous adaptive
      management of glaucoma.
AB  - We designed and tested a new rollable and implantable medical device to directly
      and continuously measure intraocular pressure. Since high intraocular pressure is
      a leading risk factor for glaucoma, such a system could solve the difficulties
      encountered in the management of this condition. In fact, glaucoma is one among
      those pathologies that could most benefit of an adaptive patient-specific
      medicine device. The presented prototype was realized with standard industrial
      microelectronic technologies (Flip-Chip on Kapton flexible PCB) and off-the-shelf
      IC components. Detailed system description and measurements, obtained during in
      vitro and laboratory characterizations, are reported. 

PMID- 24110409
TI  - An investigation of pupil-based cognitive load measurement with low cost infrared
      webcam under light reflex interference.
AB  - Using the task-evoked pupillary response (TEPR) to index cognitive load can
      contribute significantly to the assessment of memory function and cognitive
      skills in patients. However, the measurement of pupillary response is currently
      limited to a well-controlled lab environment due to light reflex and also relies
      heavily on expensive video-based eye trackers. Furthermore, commercial eye
      trackers are usually dedicated to gaze direction measurement, and their
      calibration procedure and computing resource are largely redundant for pupil
      based cognitive load measurement (PCLM). In this study, we investigate the
      validity of cognitive load measurement with (i) pupil light reflex in a less
      controlled luminance background; (ii) a low-cost infrared (IR) webcam for the
      TEPR in a controlled luminance background. ANOVA results show that with an
      appropriate baseline selection and subtraction, the light reflex is significantly
      reduced, suggesting the possibility of less constrained practical applications of
      PCLM. Compared with the TEPR from a commercial remote eye tracker, a low-cost IR
      webcam achieved a similar TEPR pattern and no significant difference was found
      between the two devices in terms of cognitive load measurement across five
      induced load levels. 

PMID- 24110410
TI  - A tactile vision substitution system for the study of active sensing.
AB  - This paper presents a tactile vision substitution system (TVSS) for the study of
      active sensing. Two algorithms, namely image processing and trajectory tracking,
      were developed to enhance the capability of conventional TVSS. Image processing
      techniques were applied to reduce the artifacts and extract important features
      from the active camera and effectively converted the information into tactile
      stimuli with much lower resolution. A fixed camera was used to record the
      movement of the active camera. A trajectory tracking algorithm was developed to
      analyze the active sensing strategy of the TVSS users to explore the environment.
      The image processing subsystem showed advantageous improvement in extracting
      object's features for superior recognition. The trajectory tracking subsystem, on
      the other hand, enabled accurately locating the portion of the scene pointed by
      the active camera and providing profound information for the study of active
      sensing strategy applied by TVSS users. 

PMID- 24110411
TI  - Prediction of 4-year risk for coronary artery calcification using ensemble-based
      classification.
AB  - The progression of coronary artery calcification (CAC) has been regarded as an
      important risk factor of coronary artery disease (CAD), which is the biggest
      cause of death. Because CAC occurrence increases the risk of CAD by a factor of
      ten, the one whose coronary artery is calcified should pay more attention to the
      health management. However, performing the computerized tomography (CT) scan to
      check if coronary artery is calcified as a regular examination might be
      inefficient due to its high cost. Therefore, it is required to identify high risk
      persons who need regular follow-up checks of CAC or low risk ones who can avoid
      unnecessary CT scans. Due to this reason, we develop a 4-year prediction model
      for a new occurrence of CAC based on data collected by the regular health
      examination. We build the prediction model using ensemble-based methods to handle
      imbalanced dataset. Experimental results show that the developed prediction
      models provided a reasonable accuracy (AUC 75%), which is about 5% higher than
      the model built by the other imbalanced classification method. 

PMID- 24110412
TI  - Improving the implementation of clinical decision support systems.
AB  - Clinical decision support (CDS) systems promise to improve the quality of
      clinical care by helping physicians to make better, more informed decisions
      efficiently. However, the design and testing of CDS systems for practical medical
      use is cumbersome. It has been recognized that this may easily lead to a
      problematic mismatch between the developers' idea of the system and requirements
      from clinical practice. In this paper, we will present an approach to reduce the
      complexity of constructing a CDS system. The approach is based on an ontological
      annotation of data resources, which improves standardization and the semantic
      processing of data. This, in turn, allows to use data mining tools to
      automatically create hypotheses for CDS models, which reduces the manual workload
      in the creation of a new model. The approach is implemented in the context of EU
      research project p-medicine. A proof of concept implementation on data from an
      existing Leukemia study is presented. 

PMID- 24110413
TI  - A temporal model for Clinical Data Analytics language.
AB  - The proposal of a special purpose language for Clinical Data Analytics (CliniDAL)
      is presented along with a general model for expressing temporal events in the
      language. The temporal dimension of clinical data needs to be addressed from at
      least five different points of view. Firstly, how to attach the knowledge of time
      based constraints to queries; secondly, how to mine temporal data in different
      CISs with various data models; thirdly, how to deal with both relative time and
      absolute time in the query language; fourthly, how to tackle internal time-event
      dependencies in queries, and finally, how to manage historical time events
      preserved in the patient's narrative. The temporal elements of the language are
      defined in Bachus Naur Form (BNF) along with a UML schema. Its use in a designed
      taxonomy of a five class hierarchy of data analytics tasks shows the solution to
      problems of time event dependencies in a highly complex cascade of queries needed
      to evaluate scientific experiments. The issues in using the model in a practical
      way are discussed as well. 

PMID- 24110414
TI  - Multivariate temporal symptomatic characterization of cardiac arrest.
AB  - We model the temporal symptomatic characteristics of 171 cardiac arrest patients
      in Intensive Care Units. The temporal and feature dependencies in the data are
      illustrated using a mixture of matrix normal distributions. We found that the
      cardiac arrest temporal signature is best summarized with six hours data prior to
      cardiac arrest events, and its statistical descriptions are significantly
      different from the measurements taken in the past two days. This matrix normal
      model can classify these patterns better than logistic regressions with lagged
      features. 

PMID- 24110415
TI  - Comparative study of probability distribution distances to define a metric for
      the stability of multi-source biomedical research data.
AB  - Research biobanks are often composed by data from multiple sources. In some
      cases, these different subsets of data may present dissimilarities among their
      probability density functions (PDF) due to spatial shifts. This, may lead to
      wrong hypothesis when treating the data as a whole. Also, the overall quality of
      the data is diminished. With the purpose of developing a generic and comparable
      metric to assess the stability of multi-source datasets, we have studied the
      applicability and behaviour of several PDF distances over shifts on different
      conditions (such as uni- and multivariate, different types of variable, and multi
      modality) which may appear in real biomedical data. From the studied distances,
      we found information-theoretic based and Earth Mover's Distance to be the most
      practical distances for most conditions. We discuss the properties and usefulness
      of each distance according to the possible requirements of a general stability
      metric. 

PMID- 24110416
TI  - Random Forest for automatic assessment of heart failure severity in a
      telemonitoring scenario.
AB  - In this study, we describe an automatic classifier of patients with Heart Failure
      designed for a telemonitoring scenario, improving the results obtained in our
      previous works. Our previous studies showed that the technique that better
      processes the heart failure typical telemonitoring-parameters is the
      Classification Tree. We therefore decided to analyze the data with its direct
      evolution that is the Random Forest algorithm. The results show an improvement
      both in accuracy and in limiting critical errors. 

PMID- 24110417
TI  - A full custom analog front-end for long-time ECG monitoring.
AB  - An analog front-end (AFE) used in portable electrocardiogram (ECG) monitoring
      devices is proposed. This AFE has included all necessary functions for the
      commercial applications. The core circuit consists of the instrumentation
      amplifier (IA), a 2(nd) order Butterworth low pass filter, and the second
      amplifying stage. The driven-right-leg circuit is integrated in the IA to
      effectively suppress the common mode interference. And the power management
      circuits provide a stable supply voltage, bias current and reference voltage for
      the other circuits. To guarantee the validity of the continuous monitoring data,
      the leadoff monitoring circuit is developed to monitor the connection of the
      leads. The chip is taped out with SMIC 0.18 um CMOS process, and the measured
      results show that the common mode rejection ratio (CMRR) and power supply
      rejection ratio (PSRR) achieve 75 dB and 90dB respectively, and the equivalent
      input referred noise is 12 uV.

PMID- 24110418
TI  - The non-contact heart rate measurement system for monitoring HRV.
AB  - A noncontact ECG monitoring and analysis system was developed using capacitive
      coupled device integrated to a home sofa. Electrodes were placed on the backrest
      of a sofa separated from the body with only the chair covering and the user's
      clothing. The study also incorporates measurements using different fabric
      materials, and a pure cotton material was chosen to cover the chair's backrest.
      The material was chosen to improve the signal to noise ratio. The system is
      initially implemented on a home sofa and is able to measure non-contact ECG
      through thin cotton clothing and perform heart rate analysis to calculate the
      heart rate variability (HRV) parameters. It was also tested under different
      conditions and results from reading and sleeping exhibited a stable ECG.
      Subsequently, results from our calculated HRV were found to be identical to those
      of a commercially available HRV analyzer. However, HRV parameters are easily
      affected by motion artifacts generated during drinking or eating with the latter
      producing a more severe disturbance. Lastly, parameters measured are saved on a
      cloud database, providing users with a long-term monitoring and recording for
      physiological information. 

PMID- 24110419
TI  - A 24 Vpp compliant biphasic stimulator for inductively powered animal behavior
      studies.
AB  - Stimulation of biological neurons using electrical charges has gained popularity
      in neuro-engineering studies. Wireless power delivery to electrical stimulators
      is an essential requirement for long term and maintenance-free implantable
      applications. Voltage compliance is often a limiting factor in these systems. We
      present an inductively powered biphasic stimulator that is capable of exhibiting
      24 Vpp load voltage compliance, while harvesting up to 13 V. The stimulator can
      deliver currents ranging from 10 uA to 6 mA. The inductive energy harvesting
      system operates at a low carrier frequency of 134.2 KHz for enhanced depth of
      penetration in biological medium. The near-field harvester works reliably for up
      to 50 mm inter-antenna distance. Noise performance and charge balancing accuracy
      have also been improved due to the absence of a boost switching circuit and
      floating current source based architecture. In-vivo motor and visual cortex
      stimulations have been performed using epi-dural screw electrodes on an awake
      behaving and anesthetized Wister rat. 

PMID- 24110420
TI  - A fully integrated 200 uW, 40 pJ/b wireless transmitter for implanted medical
      devices and neural prostheses.
AB  - In this paper we introduce a wireless transmitter suitable for implanted medical
      devices (IMDs) and neural prostheses. The transmitter achieves 500 kbps data rate
      while consuming a peak power of 200 uW from a 1.2 V supply in a 130 nm technology
      and has an active area of 35 um by 45 um. The transmitter works in the Medical
      Implant Communication Service (MICS) frequency band (401-406 MHz) and transmits
      the signal at a power of -20 dBm while achieves energy efficiency of 40 pJ/b. The
      transmitter achieves this performance through a modified pulse position
      modulation called saturated analog signal (SAS) which has been tailored to reduce
      not only the peak and average power consumption but also helps reduces the number
      of elements required for signal generation and dispenses the need for a crystal
      which in turn minimizes the overall footprint of the transmitter. The transmitter
      can also dynamically trade off duty cycling and energy consumption with data rate
      and range requirements for better operability on a constantly changing
      environment due to the inherent flexibility of the modulation scheme.

PMID- 24110421
TI  - Coupling invariant inductive link for wireless power delivery to a retinal
      prosthesis.
AB  - Inductive links are used in various applications to transfer power and data
      wirelessly. To achieve optimal performance in terms of voltage gain and maximum
      power transfer, these links are often operated at high coupling regime or under
      resonant frequency condition. However, these conditions may vary due to
      variations in the link itself or load. As a result, the link performance drops
      and the design of driving circuit become more complicated in order to compensate
      for the reduction in performance. In this work, we investigate an inductive link
      that has constant coupling. The tradeoff for invariant coupling is a reduction in
      coupling coefficient. In this study, we found that a reduction of 66 % exist
      between the traditional inductive link and our design. However, the advantage of
      coupling invariance outweighs the negative effect of large coil separation and
      varying conditions of a traditional one-pair coil link. The new link has the
      potential for powering a retinal implant. 

PMID- 24110422
TI  - Rate-equation approach to optimal density ratio of K-Rb hybrid cells for
      optically pumped atomic magnetometers.
AB  - The goal of this study is to determine optimal conditions of optically pumped
      atomic magnetometers using a hybrid cell of potassium and rubidium atoms. We
      theoretically investigated the properties of the magnetometers and considered the
      optimal density ratio of potassium and rubidium atoms. We found that the
      experimental results agreed well with the theoretical estimations and the density
      ratio of potassium and rubidium atoms should be around 200 to achieve the highest
      sensitivity. 

PMID- 24110423
TI  - Magnetic nanoparticle imaging by random and maximum length sequences of
      inhomogeneous activation fields.
AB  - Biomedical applications of magnetic nanoparticles require a precise knowledge of
      their biodistribution. From multi-channel magnetorelaxometry measurements, this
      distribution can be determined by means of inverse methods. It was recently shown
      that the combination of sequential inhomogeneous excitation fields in these
      measurements is favorable regarding the reconstruction accuracy when compared to
      homogeneous activation . In this paper, approaches for the determination of
      activation sequences for these measurements are investigated. Therefor,
      consecutive activation of single coils, random activation patterns and families
      of m-sequences are examined in computer simulations involving a sample
      measurement setup and compared with respect to the relative condition number of
      the system matrix. We obtain that the values of this condition number decrease
      with larger number of measurement samples for all approaches. Random sequences
      and m-sequences reveal similar results with a significant reduction of the
      required number of samples. We conclude that the application of pseudo-random
      sequences for sequential activation in the magnetorelaxometry imaging of magnetic
      nanoparticles considerably reduces the number of required sequences while
      preserving the relevant measurement information. 

PMID- 24110424
TI  - Magnetic rotations of uric acid crystals and uratic crystals by static magnetic
      fields of up to 500 mT.
AB  - In recent years, the disease concerning ureteral calculus is increasing possibly
      due to the changing lifestyles. For example, it is well known that the urinary
      calculi have a large impact to gout. As eating habitual diseases, gout and the
      hyper-uricemia are related to the formation of urinary calculus. In the previous
      studies, therapeutic agents were developed to enhance the uric acid excretion.
      From the viewpoint of side effects induction by the chemical agents, we are
      motivated to explore an alternative method to control the formation of ureteral
      crystals stimulator by physical stimulations. Therefore in the present study, we
      focused on the behaviors of uric acid crystals under magnetic fields of several
      hundreds of mT (Tesla). The uric acid crystals were re-crystallized from a
      suspension of uric acid powder, and the micro-crystals were prepared to be
      floating in the solution. We generated horizontal magnetic fields of maximum 500
      mT by an electromagnet which contained a CCD microscope. A permanent magnet with
      magnetic fields of 200~400 mT was also utilized. During the magnetic fields were
      applied to the uric acid crystals, we observed that the uric acid crystals were
      oriented by the magnetic fields down to 200 mT at the room temperature. It was
      speculated that the dimagnetic anisotropy in the uric acid crystals exhibited the
      rotational responses. The results indicate the possible remote control of the
      uric acid crystals in living body by the magnetic fields of 200 mT to 500 mT. 

PMID- 24110425
TI  - Design of a dual-mode electrochemical measurement and analysis system.
AB  - A dual-mode electrochemical measurement and analysis system is proposed. This
      system includes a dual-mode chip, which was designed and fabricated by using TSMC
      0.35 um 3.3 V/5 V 2P4M mixed-signal CMOS process. Two electrochemical measurement
      and analysis methods, chronopotentiometry and voltammetry, can be performed by
      using the proposed chip and system. The proposed chip and system are verified
      successfully by performing voltammetry and chronopotentiometry on solutions.

PMID- 24110426
TI  - A new radio propagation model at 2.4 GHz for wireless medical body sensors in
      outdoor environment.
AB  - This study investigates the effect of antenna height, receive antenna placement
      on human body, and distance between transmitter and receiver on the loss of
      wireless signal power in order to develop a wireless propagation model for
      wireless body sensors. Although many studies looked at the effect of distance,
      few studies were found that investigated methodically the effect of antenna
      height and antenna placement on the human body. Transmit antenna heights of 1, 2,
      and 3 meters, receive antenna heights of 1 and 1.65 meters, "on-body" and "off
      body" placements of receive antenna, and a total of 11 distances ranging from 1
      to 45 meters are tested in relation to received power in dBm. Multiple regression
      is used to analyze the data. Significance of a variable is tested by comparing
      its p-value with alpha, and model fit is assessed using adjusted R(2) and s of
      residuals. It is found that an increase in antenna height would increase power-
      but only for transmit antenna. The receive antenna height has a surprising,
      opposite effect in the on-body case and an insignificant effect in the off-body
      case. To formalize the propagation model, coefficient values from multiple
      regression are incorporated in an extension of the log-distance model to produce
      a new empirical model for on-body and off-body cases, and the new empirical model
      could conceivably be utilized to design more reliable wireless links for medical
      body sensors.

PMID- 24110427
TI  - Phase space reconstruction of an experimental model of cardiac field potential in
      normal and arrhythmic conditions.
AB  - Cardiac arrhythmias are one of the most important death causes in the world.
      Compared to the numerical models, the experimental ones provide a more realistic
      tool to study the mechanisms of cardiac arrhythmias. The in vitro culture of
      cardiac cells developed on the Multi-Electrodes Array (MEA) constitutes a
      suitable model in this context. The extracellular field potential (EFP) acquired
      from the MEA can be used to measure the electrophysiological parameters of action
      potential. In this article, the stability of this experimental model is
      investigated using the phase space reconstruction in normal and in arrhythmia
      conditions. The results show that the embedding dimension of signal EFP changed
      slightly in both cases (normal conditions and arrhythmia). The parameter time lag
      tau in the normal conditions is lower than in the arrhythmia. The shape of
      attractors remains similar but disturbed in case of arrhythmia compared to the
      normal conditions. 

PMID- 24110428
TI  - A sliding window approach to detrended fluctuation analysis of heart rate
      variability.
AB  - The analysis of heart rate variability (HRV) aids in the diagnosis of various
      diseases related to the malfunction of the autonomic nervous system. Traditional
      approaches for analysis of HRV require the signal to be reasonably stationary
      during the period of observation. This is not possible when analyzing long
      duration signals. Detrended fluctuation analysis (DFA) is robust to this issue,
      as it removes external interferences ("trends") and considers only intrinsic
      characteristics which are present throughout the signal. DFA is typically
      performed by segmenting the signal into shorter windows. This has two undesirable
      effects: (i) if the signal length is not a multiple of the window length, then at
      least one window will have fewer samples than the others; and (ii)
      discontinuities are observed on the detrended signal at the edges of each window.
      Both issues may be addressed using a sliding window. We propose and evaluate this
      idea, comparing its results with those obtained using the traditional approach.
      Experiments using different kinds of random and real HRV signals are presented.
      Statistically significant differences were observed with the proposed approach,
      especially with respect to alpha2 values. The proposed method also presented a
      great reduction in alpha1 error for white noise, which is a good model for
      congestive heart failure, with respect to alpha1 correlations. 

PMID- 24110429
TI  - Automated detection of cross-frequency coupling in the electrocorticogram for
      clinical inspection.
AB  - We developed a toolbox for detecting high-frequency oscillations and evaluating
      cross-frequency phase-amplitude coupling in electrocorticographic (ECoG) data
      with optimal parameters. Here we demonstrate use of the toolbox using simulated
      and realistic ECoG data. The results confirmed its potential usefulness for
      clinical research or practice. The tools have been released as a Phase-Amplitude
      Coupling Toolbox (PACT) plug-in for EEGLAB, an open software environment for
      electrophysiological data analysis (sccn.ucsd.edu/eeglab). 

PMID- 24110430
TI  - A study on validity of cortical alpha connectivity for schizophrenia.
AB  - Abnormalities in schizophrenia are thought to be associated with functional
      disconnections between different brain regions. Most previous studies on
      schizophrenia have considered high-band connectivity in preference to the Alpha
      band, as there has been some uncertainty correlating the latter to the condition.
      In this paper we attempt to clarify this correlation using an
      Electroencephalogram (EEG) analysis of the Alpha band from schizophrenic
      patients. Global, regional Omega and dimensional complexity and local Omega
      complexity differentials (LCD) of single channel are calculated using 16 channels
      of resting EEG data from 31 adult patients with schizophrenia and 31 age/sex
      matched control subjects. It was found that, compared to the controls, anterior
      alpha Omega and dimensional complexity are higher in schizophrenia patients
      (p<0.05) with the single channel LCD also increasing at FP1, FP2, F7 and F8
      electrodes. Furthermore, higher left hemisphere dimensional complexity and LCD at
      T3 point was also found. The results suggest there is lower connectivity in the
      pre-frontal and left temporal regions with respect to the alpha band in
      schizophrenia patients. 

PMID- 24110431
TI  - EEG source localization in full-term newborns with hypoxic-ischemia.
AB  - The aim of this study was to evaluate EEG source localization by standardized
      weighted low-resolution brain electromagnetic tomography (swLORETA) for
      monitoring of fullterm newborns with hypoxic-ischemic encephalopathy, using a
      standard anatomic head model. Three representative examples of neonatal hypoxic
      ischemia were included. The method was validated with MRI data. Hypoxic-ischemic
      areas, visible on MRI, correlated well with swLORETA current density
      distributions. In addition, neonatal seizure activity may be localized. The
      calculated current density distributions provide easy-to-interpret localized
      information about neonatal brain function, which may enable detailed longitudinal
      monitoring and potential assessment of treatment efficacy. 

PMID- 24110432
TI  - Influence of isotropic skull models on EEG source localization.
AB  - We investigated the influence of using simplified skull models on
      electroencephalogram (EEG) source localization. The simplified skull models were
      derived from CT and MR images, with isotropic conductivity modeled as either
      heterogeneous or homogeneous. A total of four simplified head models were
      compared against a reference model with a skull accurately segmented with CT
      images. Our results show that the use of a simplified geometry for the skull, can
      lead to errors of approximately 1 cm for sources located in the central and
      temporal regions of the brain. 

PMID- 24110433
TI  - Imaging and estimation of human abdominal fat by electrical impedance tomography
      using multiple voltage measurement patterns.
AB  - A measuring device for human abdominal fat from the conductivity image derived by
      electrical impedance tomography (EIT) is rarely found. This study was aimed to
      reconstruct precise conductivity images from multiple voltage measurements in
      different patterns of the combination of current and voltage electrodes. We
      examined two voltage measuring patterns using electrodes located at upper and
      lower levels around the abdomen of a subject. In the experiment, after 1024
      voltage data were taken from one specified voltage measurement pattern, another
      1024 data were also taken continuously using another pattern. The reconstruction
      of conductivity image was made using entire data. As a result, the tomography
      image was improved compared with the image obtained from single voltage
      measurement pattern. We then obtained the histogram of the conductivities and
      estimated the area of abdominal fat. The present method using multiple voltage
      measurement patterns would be effective, if the measuring time can be much
      reduced through future modification of the tomography device. 

PMID- 24110434
TI  - A realistic volume conductor model of the neonatal head: methods, challenges and
      applications.
AB  - Developing a realistic volume conductor head model is an important step towards a
      non-invasive investigation of neuro-electrical activity in the brain. For adults,
      different volume conductor head models have been designed and successfully used
      for electroencephalography (EEG) source analysis. However, creating appropriate
      neonatal volume conductor head model for EEG source analysis is a challenging
      task mainly due to insufficient knowledge of head tissue conductivities and
      complex anatomy of the developing newborn brain. In this work, we present a
      pipeline for modeling a realistic volume conductor model of the neonatal head,
      where we address the modeling challenges and propose our solutions. We also
      discuss the use of our realistic volume conductor head model for neonatal EEG
      source analysis. 

PMID- 24110435
TI  - Cortical source localization of mouse extracranial electroencephalogram using the
      FieldTrip toolbox.
AB  - Neuronal source estimation is a general tool for analyzing spatiotemporal
      dynamics in human EEG. Despite rapidly-evolving interest in human brain, there
      are few EEG based source estimation tools in rodent brain. Therefore, we
      implemented source estimation tool in a mouse model, using the FieldTrip open
      source software. High resolution EEGs with a known cortical source were recorded
      with a recently developed 40-channel polyimide-based microelectrode under optical
      stimulation on optogenetially engineered mice. To obtain realistic mouse head
      models, the volume conduction model was extracted from in vitro mouse brain MRIs.
      Segmented compartments (skin and outer/inner skull) were used to form triangular
      meshes and then applied to the boundary element method. The high-resolution EEGs
      recorded during various optogenetic stimulation of the mouse brain were inversely
      source reconstructed using minimum-norm estimate. Estimated source locations and
      strengths were reconstructed, and their error was calculated to evaluate
      FieldTrip-based source localization algorithm. In summary, source localization
      imaging of the mouse brain was successfully achieved, using freely-available open
      source software. This will be useful to investigate the functional dynamics of
      mouse brain in noninvasive measure. 

PMID- 24110436
TI  - A novel aortic valve segmentation from ultrasound image using continuous max-flow
      approach.
AB  - Geometric features of aortic valve can be applied in diagnostic, modeling and
      image-guided cardiac intervention, however methods to accurately and effectively
      delineate aortic valve from ultrasound (US) image are not well addressed. This
      paper proposes a novel aortic valve segmentation algorithm for intra-operative 2D
      short-axis US image using probability estimation and continuous max-flow (CMF)
      approach. The algorithm first calculates composite probability estimation (CPE)
      and single probability estimation (SPE) over 5 prior images based on both
      intensity and distance to the corresponding centroid, then the energy function
      for the current input image is constructed, followed by a Graphic Processing Unit
      (GPU) accelerated CMF approach to achieve aortic valve contours in approximately
      real time. Quantitative evaluations over 270 images acquired from 3 subjects
      indicated the results of the algorithm had good correlation with the manual
      segmentation results (ground truth) by an expert. The Average Symmetric Contour
      Distance (ASCD), Dice Metric (DM), and Reliability were employed to evaluate our
      algorithm, and the evaluation results of these three metrics were 1.79+/-0.46 (in
      pixels), 0.96+/-0.01 and 0.84 (d=0.95) respectively, where the computational time
      was 39.23+/-5.02 ms per frame. 

PMID- 24110437
TI  - A robust hair segmentation and removal approach for clinical images of skin
      lesions.
AB  - Artifacts such as hair are major obstacles to automatic segmentation of pigmented
      skin lesion images for computer-aided diagnosis systems. It is even more
      challenging to process clinical images taken by a regular digital camera, where
      the shadows of the skin texture may mimic hair-like curvilinear structures. In
      this study, we examined the popular DullRazor software with a dataset of 20
      clinical images. The software, specifically designed for dermoscopic images, was
      unable to remove fine hairs or hairs in the shade. Alternatively, we proposed
      using conventional matched filters to enhance curvilinear structures. The more
      complicate hair intersection patterns, which were known to generate low matched
      filtering responses, were recovered by using region growing algorithms from
      nearby detected hair segments with linear discriminant analysis (LDA) based on a
      color similarity criterion. The preliminary results indicated the proposed method
      was able to remove more fine hairs and hairs in the shade, and lower false hair
      detection rate by 58% (from 0.438 to 0.183) as compared to the DullRazor's
      approach. 

PMID- 24110438
TI  - Tubule detection in testis images using boundary weighting and circular shortest
      path.
AB  - In studies of germ cell transplantation, measureing tubule diameters and counting
      cells from different populations using antibodies as markers are very important.
      Manual measurement of tubule sizes and cell counts is a tedious and sanity
      grinding work. In this paper, we propose a new boundary weighting based tubule
      detection method. We first enhance the linear features of the input image and
      detect the approximate centers of tubules. Next, a boundary weighting transform
      is applied to the polar transformed image of each tubule region and a circular
      shortest path is used for the boundary detection. Then, ellipse fitting is
      carried out for tubule selection and measurement. The algorithm has been tested
      on a dataset consisting of 20 images, each having about 20 tubules. Experiments
      show that the detection results of our algorithm are very close to the results
      obtained manually. 

PMID- 24110439
TI  - Orientation based segmentation for phase-contrast microscopic image of confluent
      cell.
AB  - In this research, we propose a novel segmentation method for image of cultured
      cell at a confluent state, obtained by phase-contrast microscope, based on the
      orientation. First, we assign to each pixel in the image the direction of an
      eigenvector corresponding to a smaller eigenvalue of the 2 by 2 Hessian matrix
      with respect to brightness. Next, we define the orientation at a certain pixel as
      the histograms of the direction at pixels in the surrounding regions. Then, we
      evaluate deviation of histograms in the individual regions by entropy, and regard
      the series of entropy as a multi-dimensional vector, the dimension of which
      corresponds with the number of regions. We suppose that the vector is assigned to
      the pixel of interest. Finally, we segment the image based on the multi
      dimensional vector using K-means method. We investigate the efficacy of the
      proposed method using an actual human confluent fibroblast image acquired by
      phase-contrast microscopy. 

PMID- 24110440
TI  - Multi-stage intra-patient template matching for prostate detection in MR volumes.
AB  - Detecting objects, a significant task in computer vision, is accompanied with
      many challenges. When we focus on medical images, the challenges of detecting an
      organ or a tumour exhibit their own specific difficulties. Automatic finding of
      the prostate gland in magnetic resonance (MR) images, for instance, is a needed
      task in some clinical procedures. In this paper we propose a novel method for
      detection of the prostate gland in MR images. We use a multi-stage intra-patient
      approach to the template matching which is based on a trained dataset. We conduct
      experiments with the images of 100 patients and report preliminary results that
      seem to be promising. 

PMID- 24110441
TI  - On the fully automatic construction of a realistic head model for EEG source
      localization.
AB  - Accurate multi-tissue segmentation of magnetic resonance (MR) images is an
      essential first step in the construction of a realistic finite element head
      conductivity model (FEHCM) for electroencephalography (EEG) source localization.
      All of the segmentation approaches proposed to date for this purpose require
      manual intervention or correction and are thus laborious, time-consuming, and
      subjective. In this paper we propose and evaluate a fully automatic method based
      on a hierarchical segmentation approach (HSA) incorporating Bayesian-based
      adaptive mean-shift segmentation (BAMS). An evaluation of HSA-BAMS, as well as
      two reference methods, in terms of both segmentation accuracy and the source
      localization accuracy of the resulting FEHCM is also presented. The evaluation
      was performed using (i) synthetic 2D multi-modal MRI head data and synthetic EEG
      (generated for a prescribed source), and (ii) real 3D T1-weighted MRI head data
      and real EEG data (with expert determined source localization). Expert manual
      segmentation served as segmentation ground truth. The results show that HSA-BAMS
      outperforms the two reference methods and that it can be used as a surrogate for
      manual segmentation for the construction of a realistic FEHCM for EEG source
      localization. 

PMID- 24110442
TI  - Molecular biological characteristics based Hierarchical Mumford-Shah Vector-Model
      for the delineation of biological target volumes corresponding to head and neck
      tumors.
AB  - To more accurately and precisely delineate a biologic target volume (BTV) for the
      positron emission tomography (PET)-guided radiotherapy treatment planning, we
      proposed a novel Hierarchical Mumford-Shah Vector Model (HMSMv), where the image
      vector was composed of the molecular biological characteristics such as contrast,
      busyness and the standard uptake value (SUV) of tumors. The BTV was delineated
      via the propagation of the level set flow of the proposed HMSMv. The propagation
      took place inside a ring-volume of interest (VOI) which was defined by an
      adaptive volume-growing algorithm based on the PET SUV, contrast and busyness of
      a tumor. Four patient studies were assessed and visually inspected by two
      radiation oncologists (Suyu Zhu and Zaijie Huang). Compared the resulting BTV
      with the gross target volume (GTV) of one patient study, the sensitivity,
      specificity and similarity were 92.28%, 87.29%, 79.28% respectively. Moreover,
      all of four BTVs were between the corresponding GTV and planning target volume
      (PTV). Most of the BTVs were between the GTV and the clinical target volume
      (CTV). The results demonstrated that the proposed method can delineate the BTVs
      of nasopharyngeal carcinomas more accurately and precisely than the manual
      delineation and also the threshold segmentation method with SUV of 2.5 as the
      threshold. The GTV, CTV, and PTV were manually delineated by the two radiation
      oncologists based on PET, CT and MRI images for the intensity modulated
      radiotherapy (IMRT) planning of the four patients. 

PMID- 24110443
TI  - An automatic brain tumor segmentation tool.
AB  - This paper introduces an automatic brain tumor segmentation method (ABTS) for
      segmenting multiple components of brain tumor using four magnetic resonance image
      modalities. ABTS's four stages involve automatic histogram multi-thresholding and
      morphological operations including geodesic dilation. Our empirical results, on
      16 real tumors, show that ABTS works very effectively, achieving a Dice accuracy
      compared to expert segmentation of 81% in segmenting edema and 85% in segmenting
      gross tumor volume (GTV). 

PMID- 24110444
TI  - Automated IMT estimation and BMI correlation using a low-quality carotid
      ultrasound image database from India.
AB  - This paper presents AtheroEdgeLowRes (AELR), an extention of AtheroEdgeTM from
      AtheroPointTM, and a solution to carotid ultrasound IMT measurement in low
      resolution and overall low quality images. The images were collected using a low
      end ultrasound machine during a screening study in India. We aim to demonstrate
      the accuracy and reproducibility of the AELR system by benchmarking it against an
      expert Reader's manual tracing and to show the correlation between the
      automatically measured intima media thickness (IMT) and the subjects'
      cardiovascular risk factors (i.e. body mass index--BMI). We introduced an
      innovative penalty function (PF) to our dual-snake segmentation technique,
      necessary due to the low image resolution. We processed 512 images from 256
      patients, and correlated the AELR IMT values with the patients' age and BMI. AELR
      processed all 512 images, and the IMT measurement error was 0.011+/-0.099 mm with
      the PF correction and 0.173+/-0.127 mm without. AELR IMT values correlated with
      the Reader's values (r = 0.883) and also correlated with the subject's BMI and
      age. The AELR system showed accuracy and reproducibility levels that make it
      suitable to be used in large epidemiological and screening studies in emerging
      countries.

PMID- 24110445
TI  - Segmentation of hepatic tumor from abdominal CT data using an improved support
      vector machine framework.
AB  - An improved support vector machine (SVM) framework has been developed to segment
      hepatic tumor from CT data. By this method, the one-class SVM (OSVM) and two
      class SVM (TSVM) are connected seamlessly by a boosting tool, to tackle the tumor
      segmentation via both offline and online learning. An initial tumor region was
      first pre-segmented by an OSVM classifier. Then the boosting tool was employed to
      automatically generate the negative (non-tumor) samples, according to certain
      criteria. The pre-segmented initial tumor region and the non-tumor samples
      generated were used to train a TSVM) classifier. By the trained TSVM classifier,
      the final tumor lesion was segmented out. Tested on 16 sets of CT abdominal
      scans, quantitative results suggested that the developed method achieved
      significantly higher segmentation accuracy than the OSVM and TSVM classifiers. 

PMID- 24110446
TI  - 3-D segmentation of human sternum in lung MDCT images.
AB  - A fully automatic novel algorithm is presented for accurate 3-D segmentation of
      the human sternum in lung multi detector computed tomography (MDCT) images. The
      segmentation result is refined by employing active contours to remove calcified
      costal cartilage that is attached to the sternum. For each dataset, costal
      notches (sternocostal joints) are localized in 3-D by using a sternum mask and
      positions of the costal notches on it as reference. The proposed algorithm for
      sternum segmentation was tested on 16 complete lung MDCT datasets and comparison
      of the segmentation results to the reference delineation provided by a
      radiologist, shows high sensitivity (92.49%) and specificity (99.51%) and small
      mean distance (dmean=1.07 mm). Total average of the Euclidean distance error for
      costal notches positioning in 3-D is 4.2 mm. 

PMID- 24110447
TI  - An automated algorithm for blood vessel count and area measurement in 2-D
      choroidal scan images.
AB  - We present an automated algorithm for the detection of blood vessels in 2-D
      choroidal scan images followed by a measurement of the area of the vessels. The
      objective is to identify vessel parameters in the choroidal stroma that are
      affected by various abnormalities. The algorithm is divided into five stages. In
      the first stage, the image is denoised to remove sensor noise and facilitate
      further processing. In the second stage, the image is segmented in order to find
      the region of interest. In the third stage, three different contour detection
      methods are applied to address different challenges in vessel contour. In the
      fourth stage, the outputs of the three contour detection methods are combined to
      achieve refined vessel contour detection. In the fifth and final stage, the area
      of these contours are measured. The results have been evaluated by a practicing
      opthalmologist and performance of the algorithm relative to expert detection is
      reported. 

PMID- 24110448
TI  - Cerebrospinal fluid image segmentation using spatial fuzzy clustering method with
      improved evolutionary Expectation Maximization.
AB  - Visualization of cerebrospinal fluid (CSF), that flow in the brain and spinal
      cord, plays an important role to detect neurodegenerative diseases such as
      Alzheimer's disease. This is performed by measuring the substantial changes in
      the CSF flow dynamics, volume and/or pressure gradient. Magnetic resonance
      imaging (MRI) technique has become a prominent tool to quantitatively measure
      these changes and image segmentation method has been widely used to distinguish
      the CSF flows from the brain tissues. However, this is often hampered by the
      presence of partial volume effect in the images. In this paper, a new hybrid
      evolutionary spatial fuzzy clustering method is introduced to overcome the
      partial volume effect in the MRI images. The proposed method incorporates
      Expectation Maximization (EM) method, which is improved by the evolutionary
      operations of the Genetic Algorithm (GA) to differentiate the CSF from the brain
      tissues. The proposed improvement is incorporated into a spatial-based fuzzy
      clustering (SFCM) method to improve segmentation of the boundary curve of the CSF
      and the brain tissues. The proposed method was validated using MRI images of
      Alzheimer's disease patient. The results presented that the proposed method is
      capable to filter the CSF regions from the brain tissues more effectively
      compared to the standard EM, FCM, and SFCM methods. 

PMID- 24110449
TI  - Learning metrics for content-based medical image retrieval.
AB  - Application of content-based image retrieval (CBIR) to medical image analysis has
      recently become an active research field. While many previous studies have
      focused on the feature design, the metric design, another key CBIR component, has
      not been well investigated in this application context. This paper presents a
      medical CBIR that adapts its similarity metric from data by using information
      theoretic metric learning. Also we systematically compare our SIFT bag-of-words
      based system with various plug-in similarity measures available in literature.
      The proposed systems are evaluated with the ImageCLEF-2011 benchmarking dataset.
      Our experimental results demonstrate the advantage of the proposed metric
      learning approach and L1 distance-based measures.

PMID- 24110450
TI  - Volumetric surgical planning system for fibular transfer in mandibular
      reconstruction.
AB  - This presentation introduces a new software design for virtual preoperative
      planning for free fibular transfer in mandibular reconstructive surgery. Direct
      volume resection and manipulation of superimposed fibular segments allow
      interactive editing of the surgical plan without the need for a surface modeling
      process. We also introduce three shape indicators: volume ratio, contour error
      and maximum projection for evaluating the reconstruction plan from geometrical
      aspects. The indicators significantly quantify the difference between 2-segment
      and 3-segment cases, and suggest optimization of preoperative planning while
      satisfying appropriate placement margins for fibular segments. 

PMID- 24110451
TI  - Image fusion improvements applied at the generation of 3D thermal models.
AB  - The application of multimodal image registration to various medical applications
      has been investigated. Image fusion involving 3D thermal and MRI/CT images allows
      the extraction of both functional and anatomical information, which may become a
      powerful tool to aid in clinical diagnoses. This paper presents innovations at
      the image fusion methodology, which currently requires that both imaging
      modalities are represented and visualized at the same 3D viewing projection. The
      proposed solution is based and compared with two different viewing projections:
      orthogonal and perspective. The methodology requires that the thermographic
      images (or photographs) are visualized in the orthogonal view, in order to match
      with the 2D projected images (using range images) from MRI/CT. The results
      obtained have shown significant improvements in the 3D thermal models, when
      compared and evaluated with the perspective approach. This allowed the generation
      of more accurate 3D models, which match both the geometry and texture (functional
      temperature information). Since it is desirable to combine or unify more than one
      imaging modality, these 3D multimodal models may have a strong impact in many
      clinical applications.

PMID- 24110452
TI  - Compressibility variations of JPEG2000 compressed computed tomography.
AB  - Compression is increasingly used in medical applications to enable efficient and
      universally accessible electronic health records. However, lossy compression
      introduces artifacts that can alter diagnostic accuracy, interfere with image
      processing algorithms and cause liability issues in cases of diagnostic errors.
      Compression guidelines were introduced to mitigate these issues and foster the
      use of modern compression algorithms with diagnostic imaging. However, these
      guidelines are usually defined as maximum compression ratios for each imaging
      protocol and do not take compressibility variations due to image content into
      account. In this paper we have evaluated the compressibility of thousands of
      computed tomography slices of an anthropomorphic thoracic phantom acquired with
      different parameters. We have shown that exposure, slice thickness and
      reconstruction filters have a significant impact on compressibility suggesting
      that guidelines based solely on compression ratios may be inadequate. 

PMID- 24110453
TI  - Fast and robust 3D vertebra segmentation using statistical shape models.
AB  - We propose a top-down fully automatic 3D vertebra segmentation algorithm using
      global shape-related as well as local appearance-related prior information. The
      former is brought into the system by a global statistical shape model built from
      annotated training data, i.e., annotated CT volumes. The latter is handled by a
      machine learning-based component, i.e., a boundary detector, providing a strong
      discriminative model for vertebra surface appearance by making use of local
      context-encoding features. This boundary detector, which is essentially a
      probabilistic boosting-tree classifier, is also learnt from annotated training
      data. Contextual information is taken into account by representing vertebra
      surface candidate voxels with high-dimensional vectors of 3D steerable features
      derived from the observed volume intensities. Our system does not only consider
      the body of the individual vertebrae but also the spinal processes. Before
      segmentation, the image parts depicting individual vertebrae are spatially
      normalized with respect to their bounding box information in terms of
      translation, orientation, and scale leading to more accurate results. We evaluate
      segmentation accuracy on 7 CT volumes each depicting 22 vertebrae. The results
      indicate a symmetric point-to-mesh surface error of 1.37 +/- 0.37 mm, which
      matches the current state-of-the-art. 

PMID- 24110454
TI  - Combination of intra-operative freehand SPECT imaging with MR images for guidance
      and navigation.
AB  - Nowadays for clinical applications such as sentinel lymph node biopsy in breast
      or prostate cancer, only pre-operative image data is used for navigation, i.e.
      CT, SPECT/CT or PET/CT. Freehand SPECT and freehand PET provide intra-operative
      functional imaging techniques that can be complemented with pre- and intra
      operative MR imaging to allow for better planning, navigation and guidance. In
      this paper we propose a method to enable navigation based on pre- or intra
      operatively acquired MR images. A fully MR compatible phantom and a dedicated MR
      compatible optical tracking target with MR markers is built for this study.
      PET/MR, SPECT/CT and freehand SPECT scans of the phantom are performed.
      Registration is done using point based registration of the known marker and
      target geometries and a ground truth is obtained from a SPECT/CT and an MR image
      that are directly registered. The RMS errors was 0.31 mm for the ground truth and
      3.29 mm when using segmentation of the MR markers and their spatial relationship
      with the optical tracking spheres of the dedicated target. Thus, the freehand
      SPECT can be registered easily by this approach without the need of any
      additional CT scans and therefore without any additional radiation dose for the
      patient. This enables intra-operative fusion of the pre- or intra-operatively
      acquired MR data, which could provide valuable additional information for intra
      operative applications such as guidance based on accurate anatomy or verifying
      exact tumor location in combination with detailed morphological patient data.

PMID- 24110455
TI  - Composite imaging method for histological image analysis.
AB  - A composite imaging method has been developed that enables the user to directly
      capture a composite image by one-image capturing. It was experimentally verified
      that the composite images of bright-field, dark-field, and phase-contrast images
      can be captured with an arbitrary composition ratio. The difference in pixel
      values between the captured composite image and the computer composite image was
      small. This imaging method is realized only by placing below the condenser a
      masking plate, which can easily be made using Neutral Density filters. Therefore,
      little additional time and cost are needed. The composite imaging method was
      applied for extracting Helicobacter pylori in microscopic images of HE-stained
      gastric histological sections. H. pylori is difficult to extract because the
      colors in H. pylori are similar to those in other areas. It is experimentally
      shown that a composite image of phase-contrast and dark-field images captured
      using the proposed method improves the accuracy for extracting H. pylori.

PMID- 24110456
TI  - Removal of stimulus-induced artifacts in functional spinal cord imaging.
AB  - This paper develops a novel method to reduce the influence of stimulus-induced
      artifacts in functional spinal cord imaging. The developed method employes a two
      step procedure. The first step acquires artifact data, which contain artifacts
      but do not contain spinal cord evoked magnetic field (SCEF). The second step
      applies a method called common-mode subspace projection (CSP). The effectiveness
      of the developed method is validated using SCEF data measured from a healthy
      volunteer. 

PMID- 24110457
TI  - An improved method for IR image filtering from living beings.
AB  - A new method to enhancing the quality of the images acquired with infrared camera
      is presented. Usually, thermal image filtering process relies on heat conductive
      component that propagates through tissue. An improved method for nonlinear
      filtering is presented in this article. A new component of the heat, the
      convection is associated heat that propagates through the tissues of living
      beings. From the physical point of view, this component is the result of blood
      flow through the tissue. The proposed algorithm uses both parts of the heat
      components and iteratively minimizes the noise that is added to the signal.
      During the iterative filtering process, the noise is more quickly minimized than
      other methods can do. Thermal contour shape is an important indicator for
      oncologists to diagnose superficial cancers such as breast, thyroid and skin. The
      proposed method has been tested on more patients and an example of an IR image
      filtering taken from a patient suffering from papillary carcinoma is shown at
      different iterations. The algorithm convergence speed and the contour shape are
      compared with the results obtained by using anisotropic filtering. 

PMID- 24110458
TI  - Automatic removal of manually induced artefacts in ultrasound images of thyroid
      gland.
AB  - Manually induced artefacts, like caliper marks and anatomical labels, render an
      ultrasound (US) image incapable of being subjected to further processes of
      Computer Aided Diagnosis (CAD). In this paper, we propose a technique to remove
      these artefacts and restore the image as accurately as possible. The technique
      finds application as a pre-processing step when developing unsupervised
      segmentation algorithms for US images that deal with automatic estimation of the
      number of segments and clustering. The novelty of the algorithm lies in the image
      processing pipeline chosen to automatically identify the artefacts and is
      developed based on the histogram properties of the artefacts. The algorithm was
      able to successfully restore the images to a high quality when it was executed on
      a dataset of 18 US images of the thyroid gland on which the artefacts were
      induced manually by a doctor. Further experiments on an additional dataset of 10
      unmarked US images of the thyroid gland on which the artefacts were simulated
      using Matlab showed that the restored images were again of high quality with a
      PSNR > 38 dB and free of any manually induced artefacts.

PMID- 24110459
TI  - Comparison of a discrete wavelet transform method and a modified undecimated
      discrete wavelet transform method for denoising of mammograms.
AB  - The purpose of this study was to evaluate the performance of a conventional
      discrete wavelet transform (DWT) method and a modified undecimated discrete
      wavelet transform (M-UDWT) method applied to mammographic image denoising. Mutual
      information, mean square error, and signal to noise ratio were used as image
      quality measures of images processed by the two methods. We examined the
      performance of the two methods with visual perceptual evaluation. A two-tailed F
      test was used to measure statistical significance. The difference between the M
      UDWT processed images and the conventional DWT-method processed images was
      statistically significant (P<0.01). The authors confirmed the superiority and
      effectiveness of the M-UDWT method. The results of this study suggest the M-UDWT
      method may provide better image quality as compared to the conventional DWT. 

PMID- 24110460
TI  - Application of the real-time Retinex image enhancement for endoscopic images.
AB  - This paper presents a real-time image enhancement technique for gastric
      endoscopy, which is based on the variational approach of the Retinex theory. In
      order to efficiently reduce the computational cost required for image
      enhancement, processing layers and repeat counts of iterations are determined in
      accordance with software evaluation result, and as for processing architecture,
      the pipelining architecture can handle high resolution pictures in real-time. To
      show its potential, performance comparison between with and without the proposed
      image enhancement technique is shown using several video images obtained by
      endoscopy for different parts of digestive organ. 

PMID- 24110461
TI  - Projection Onto Convex Sets (POCS) method for photoacoustic tomography with a non
      negative constraint.
AB  - Photoacoustic imaging is a biomedical imaging modality capable of early cancer
      detection. In this paper, we proposed a novel iterative Projections Onto Convex
      Sets (POCS) method for improving photoacoustic reconstruction. This method aims
      to obtain a non negative pressure distribution satisfying the measured signals.
      This POCS method is performed in the Fourier Bessel space avoiding matrix
      inversions in the projections, speeding up projections and is capable of handling
      the large data sets present in photoacoustic imaging. The numerical experiments
      performed showed that improved reconstruction was obtained with a few iterations
      together with the recovery of some lost information. 

PMID- 24110462
TI  - A two-stage reconstruction of fluorescence molecular tomography based on sparse
      regularization.
AB  - Fluorescence molecular tomography (FMT) is a promising imaging modality that
      offers the possibilities to monitor cellular and molecular function in vivo.
      However, accurate and stable reconstruction of fluorescence-labeled targets
      remains a challenging problem. In this contribution, a two-stage reconstruction
      algorithm that combines sparse regularization with adaptive finite element method
      is proposed, and two different inversion algorithms are employed separately on
      the initial coarse mesh and the second refined one. Numerical experiment results
      with a digital mouse model demonstrate the stability and computational efficiency
      of the proposed method for FMT. 

PMID- 24110463
TI  - Fusion of lung MR/CT images through lung vessel registration.
AB  - Lung perfusion analysis with sequential contrasted MRI is an important clinical
      tool. This work is part of larger research in which the objective of fusing lung
      perfusion analysis and lung anatomical structures. In this work, it is proposed a
      multimodality MR/CT lung fusion algorithm based on lung vessel determination that
      analyzes lung perfusion. 3D contrasted MR and 3D CT images are first normalized
      (slice thickness, resolution and pixel intensity), then lung features are
      determined and elastically registered. The registration algorithm was checked by
      mapping in both directions, from MR to CT and vice-versa. A MR perfusion analysis
      result is fused with a 3D CT segmented lung vessel tree. 

PMID- 24110464
TI  - A basic study on variable-gain Kalman filter based on angle error calculated from
      acceleration signals for lower limb angle measurement with inertial sensors.
AB  - In this study, development of wearable motion measurement system using inertial
      sensors has been focused with the aim of rehabilitation support. For measurement
      of lower limb joint angles with inertial sensors, Kalman-filtering-based angle
      measurement method was developed. However, it was required to reduce variation of
      measurement errors that depended on movement speeds or subjects. In this report,
      variable-gain Kalman filter based on the difference between the estimated angle
      by the Kalman filter and the angle calculated from acceleration signals was
      tested. From angle measurement during treadmill walking with healthy subjects, it
      was shown that measurement accuracy of the foot inclination angle was
      significantly improved with the proposed method compared to the method of fixed
      parameter value. 

PMID- 24110465
TI  - A trial of making reference gait data for simple gait evaluation system with
      wireless inertial sensors.
AB  - Recently, the use of wearable inertial sensors have been widely studied in the
      field of human movement analysis. Our research group developed a wearable motion
      measurement system using the wireless inertial sensors for rehabilitation
      training and daily exercise. However, there are few reference data to evaluate
      motor function. In this paper, reference data of joint and inclination angles of
      lower limb and that of gait event timing for gait evaluation were made by
      measurement with 4 healthy subjects in their twenties. Average values of
      inclination and joint angles and gait event timings were similar to those seen in
      literature. These suggest that the averaged data obtained in this paper can be
      used as reference data. Then, gait data of a healthy subject in his thirties were
      compared with the reference data. Most of angles and all the gait event timings
      were considered to be standard of 20's. However, some angles of the healthy
      subject in his thirties were considered not to be the standard partly. These
      differences in evaluation were considered to depend on a level of similarity of
      movement to the reference data. It was expected to evaluate the level of
      similarity of movement from various parameters. 

PMID- 24110466
TI  - An approach to analyze the movements of the arms while walking using wearable
      wireless devices.
AB  - Rhythmic movement of the arms while walking is an important feature of human
      gait. In this paper, we present an approach to analyze the movements of the arms
      while walking by using three wearable wireless devices placed around the torso.
      One of the devices is transmitter placed at the back and the other two are
      symmetrically placed receivers that record the power variation due to movements
      of the arms while walking. We show that the power received by the receivers will
      have symmetrical variation if the arms' swing is symmetrical. An analytical model
      has been used to calculate the position of the receivers. Full wave simulations
      on a walking phantom are done to confirm the results. 

PMID- 24110467
TI  - Mobile Motion Capture--MiMiC.
AB  - The low cost, simple, robust, mobile, and easy to use Mobile Motion Capture
      (MiMiC) system is presented and the constraints which guided the design of MiMiC
      are discussed. The MiMiC Android application allows motion data to be captured
      from kinematic modules such as Shimmer 2r sensors over Bluetooth. MiMiC is cost
      effective and can be used for an entire day in a person's daily routine without
      being intrusive. MiMiC is a flexible motion capture system which can be used for
      many applications including fall detection, detection of fatigue in industry
      workers, and analysis of individuals' work patterns in various environments. 

PMID- 24110468
TI  - Piezoelectric and electromagnetic respiratory effort energy harvesters.
AB  - The movements of the torso due to normal breathing could be harvested as an
      alternative, and renewable power source for an ultra-low power electronic device.
      The same output signal could also be recorded as a physiological signal
      containing information about breathing, thus enabling self-powered wearable
      biosensors/harvesters. In this paper, the selection criteria for such a
      biosensor, optimization procedure, trade-offs, and challenges as a sensor and
      harvester are presented. The empirical data obtained from testing different
      modules on a mechanical torso and a human subject demonstrated that an
      electromagnetic generator could be used as an unobtrusive self-powered medical
      sensor by harvesting more power, offering reasonable amount of output voltage for
      rectification purposes, and detecting respiratory effort. 

PMID- 24110469
TI  - Touch interface for sensing fingertip force in mobile device using
      electromyogram.
AB  - The aim of this study is to develop a three-dimensional touch interface for
      mobile devices, specifically a touch interface for detecting fingertip force.
      This interface consists of a conventional touch interface and an electromyogram
      (EMG) amplifier. The fingertip force during manipulation of the touch interface
      is estimated from the EMG measurement. We develop a method for obtaining
      fingertip force information using an EMG, while the two-dimensional position of
      the finger is measured using the conventional touch interface found in mobile
      devices. Further, we evaluate the validity of our newly developed interface by
      comparing the fingertip force estimated using our proposed method with the
      fingertip force measured using a force sensor. Lastly, we develop an application
      using our interface. 

PMID- 24110470
TI  - The rectenna design on contact lens for wireless powering of the active
      intraocular pressure monitoring system.
AB  - This paper proposed a wireless power harvesting system with micro-electro
      mechanical-systems (MEMS) fabrication for noninvasive intraocular pressure (IOP)
      measurement on soft contact lens substructure. The power harvesting IC consists
      of a loop antenna, an impedance matching network and a rectifier. The proposed IC
      has been designed and fabricated by CMOS 0.18 um process that operates at the ISM
      band of 5.8 GHz. The antenna and the power harvesting IC would be bonded together
      by using flip chip bonding technologies without extra wire interference. The
      circuit utilized an impedance transformation circuit to boost the input RF signal
      that improves the circuit performance. The proposed design achieves an RF-to-DC
      conversion efficiency of 35% at 5.8 GHz.

PMID- 24110471
TI  - 1.2 V constant-gm rail-to-rail CMOS Op-Amp input stage with new overlapped
      transition regions technique for ECG amplifier.
AB  - The conventional technique of overlapped transition regions for producing a
      constant transconductance rail to rail Op-Amp input stage can only tolerate a
      limited amount of voltage shifting. This is limited by the minimum Vgs required
      for active mode operation of transistors. In this paper, we present a novel
      overlapped transition regions technique that overcomes the limitation of the
      conventional technique. This new overlapped transition regions technique has no
      voltage shifting limit. For both N-type and P-type conventional complementary
      differential input pairs, one source follower and one MOSFET are added to control
      the saturation point of current of input pairs. For 1.2 V single supply voltage,
      simulation results demonstrate +/-3.71% of overall transconductance variation.
      Cadence SPECTRE simulator and TSMC 0.25-um CMOS technology are used to layout and
      simulate this work.

PMID- 24110472
TI  - A Bayesian framework for identifying cell migration dynamics.
AB  - Cell migration is a vital process in living organisms. In particular we are
      interested in the way that white blood cells such as neutrophils migrate during
      episodes of inflammation which are important events in the working of the innate
      immune system. Migration of populations of many kinds can be modelled using drift
      diffusion models by drawing analogies between the individual agents and the
      molecules in a fluid. It is challenging to arrive at a data-driven estimate of
      the parameters of this kind of process, particularly so if the individual agents
      have time varying properties that are not uniform over the population. In this
      paper, we offer a novel framework to estimate migration dynamics in this context.
      It makes use of the Approximate Bayesian Computation approach for parameter
      estimation and model selection. The Framework is applied to zebrafish neutrophil
      dynamics but is applicable for general migration scenarios. 

PMID- 24110473
TI  - Identifying candidate disease genes using a trace norm constrained bipartite
      raking model.
AB  - Computational prediction of genes that play roles in human diseases remains an
      important but challenging task. In this work, we formulate candidate gene
      prediction as a bipartite ranking problem combining a task-wise ordered
      observation model with a latent multitask regression function using the matrix
      variate Gaussian process (MV-GP). We then use a trace-norm constrained
      variational inference approach to obtain the bipartite ranking model variables
      and the parameters of the underlying multitask regression model. We use this
      model to predict candidate genes from two gene-disease association data sets and
      show that our model outperforms current state-of-the-art methods. Finally, we
      demonstrate the practical utility of our method by successfully recovering well
      characterized gene-disease associations hidden in our training data. 

PMID- 24110474
TI  - A novel framework for exploratory analysis of highly variable morphology of
      migrating epithelial cells.
AB  - Migratory cells, for example human retinal epithelial (RPE) cells, exhibit highly
      variable morphology. This makes it difficult to use traditional methods, such as
      the landmark based Procrustes analysis or feature based analysis, to
      quantitatively represent their shapes. We propose a novel framework to generate a
      low-dimensional representation of highly variable cell shapes. The framework
      lends itself readily to efficient exploratory analysis of a given cell shape
      dataset in order to visualise morphological trends in the data and reveal the
      intrinsic structure of various morphology-based cell phenotypes in the data.
      Preliminary results show that the framework is effective in revealing consistent
      morphological phenotypes. 

PMID- 24110475
TI  - A software tool for the selection of tandem repeats for MLVA analysis.
AB  - DNA fingerprinting is a reliable tool for identifying, tracing and characterizing
      bacterial clonal population structure. A recent technique is given by the
      Multiple Loci VNTR Analysis (MLVA), where VNTR denotes Variable Number of Tandem
      Repeats, that meets the need for fast and reliable typing methods by combining
      the polymorphic nature of tandem repeats (TR) and the use of Polymerase Chain
      Reaction (PCR) methodology. The key point in the MLVA technique is the selection
      of a set of TRs which have a sufficient variability (polymorphism) across
      strains, in order to allow easy strain typing. In this work, we present a program
      which analyses a set of N genomes and outputs the list of shared TRs and
      associated information. The program compares the TRs for each possible genome
      pair, and finds the sets of TRs that are shared by at least M genomes. The
      subsequent determination of "virtual amplicons" enables the user to consider the
      actual polymorphism exhibited by the different strains with regards to each given
      TR, which is the critical parameter for the experimental strain typing.

PMID- 24110476
TI  - Muscle synergy control model-tuned EMG driven torque estimation system with a
      musculo-skeletal model.
AB  - Muscle activity is the final signal for motion control from the brain. Based on
      this biological characteristic, Electromyogram (EMG) signals have been applied to
      various systems that interface human with external environments such as external
      devices. In order to use EMG signals as input control signal for this kind of
      system, the current EMG driven torque estimation models generally employ the
      mathematical model that estimates the nonlinear transformation function between
      the input signal and the output torque. However, these models need to estimate
      too many parameters and this process cause its estimation versatility in various
      conditions to be poor. Moreover, as these models are designed to estimate the
      joint torque, the input EMG signals are tuned out of consideration for the
      physiological synergetic contributions of multiple muscles for motion control. To
      overcome these problems of the current models, we proposed a new tuning model
      based on the synergy control mechanism between multiple muscles in the cortico
      spinal tract. With this synergetic tuning model, the estimated contribution of
      multiple muscles for the motion control is applied to tune the EMG signals. Thus,
      this cortico-spinal control mechanism-based process improves the precision of
      torque estimation. This system is basically a forward dynamics model that
      transforms EMG signals into the joint torque. It should be emphasized that this
      forward dynamics model uses a musculo-skeletal model as a constraint. The musculo
      skeletal model is designed with precise musculo-skeletal data, such as origins
      and insertions of individual muscles or maximum muscle force. Compared with the
      mathematical model, the proposed model can be a versatile model for the torque
      estimation in the various conditions and estimates the torque with improved
      accuracy. In this paper, we also show some preliminary experimental results for
      the discussion about the proposed model. 

PMID- 24110477
TI  - Estimating a ranked list of human hereditary diseases for clinical phenotypes by
      using weighted bipartite network.
AB  - With the availability of the huge medical knowledge data on the Internet such as
      the human disease network, protein-protein interaction (PPI) network, and
      phenotypegene, gene-disease bipartite networks, it becomes practical to help
      doctors by suggesting plausible hereditary diseases for a set of clinical
      phenotypes. However, identifying candidate diseases that best explain a set of
      clinical phenotypes by considering various heterogeneous networks is still a
      challenging task. In this paper, we propose a new method for estimating a ranked
      list of plausible diseases by associating phenotypegene with gene-disease
      bipartite networks. Our approach is to count the frequency of all the paths from
      a phenotype to a disease through their associated causative genes, and link the
      phenotype to the disease with path frequency in a new phenotype-disease bipartite
      (PDB) network. After that, we generate the candidate weights for the edges of
      phenotypes with diseases in PDB network. We evaluate our proposed method in terms
      of Normalized Discounted Cumulative Gain (NDCG), and demonstrate that we
      outperform the previously known disease ranking method called Phenomizer. 

PMID- 24110478
TI  - Dynamic contrast enhanced optical imaging of cervix, in vivo: a paradigm for
      mapping neoplasia-related parameters.
AB  - We present a novel biophotonic method and imaging modality for estimating and
      mapping neoplasia-specific functional and structural parameters of the cervical
      precancerous epithelium. Estimations were based on experimental data obtained
      from dynamic contrast-enhanced optical imaging of cervix, in vivo. We have
      developed a pharmacokinetic, in silico, model of the optical tracer's uptake by
      the epithelium. We have identified that the kinetic parameters of the model
      correlate well with pathologic alterations in both metabolic and structural
      characteristics of the tissue, associated with the neoplasia progress. Global
      sensitivity analysis and global optimization methods were employed for
      identifying the key determinant set of biological parameters that dictate the
      model's output. Particularly, the shuffled complex evolution algorithm converged
      to a set of four parameters that can be estimated with an error of 7%, indicating
      a good accuracy and precision. These results are unique in the sense that for the
      first time functional and microstructural parameter maps can be estimated and
      displayed together, thus maximizing the diagnostic information. The quantity and
      the quality of this information are unattainable by other invasive and non
      invasive methods. 

PMID- 24110479
TI  - Hypnosis control based on the minimum concentration of anesthetic drug for
      maintaining appropriate hypnosis.
AB  - This paper proposes a novel hypnosis control method using Auditory Evoked
      Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an
      anesthetic drug, it is desirable to reduce the amount of an anesthetic drug
      during surgery. For this purpose many studies of hypnosis control systems have
      been done. Most of them use Bispectral Index (BIS), another hypnosis index, but
      it has problems of dependence on anesthetic drugs and nonsmooth change near some
      particular values. On the other hand, aepEX has an ability of clear distinction
      between patient consciousness and unconsciousness and independence of anesthetic
      drugs. The control method proposed in this paper consists of two elements:
      estimating the minimum effect-site concentration for maintaining appropriate
      hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model
      predictive control. The minimum effect-site concentration is estimated utilizing
      the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted
      so that effect-site concentration of propofol may be kept near and always above
      the minimum effect-site concentration. Simulation results of hypnosis control
      using the proposed method show that the minimum concentration can be estimated
      appropriately and that the proposed control method can maintain hypnosis
      adequately and reduce the total infusion amount of propofol. 

PMID- 24110480
TI  - Personalized tuning of a reinforcement learning control algorithm for glucose
      regulation.
AB  - Artificial pancreas is in the forefront of research towards the automatic insulin
      infusion for patients with type 1 diabetes. Due to the high inter- and intra
      variability of the diabetic population, the need for personalized approaches has
      been raised. This study presents an adaptive, patient-specific control strategy
      for glucose regulation based on reinforcement learning and more specifically on
      the Actor-Critic (AC) learning approach. The control algorithm provides daily
      updates of the basal rate and insulin-to-carbohydrate (IC) ratio in order to
      optimize glucose regulation. A method for the automatic and personalized
      initialization of the control algorithm is designed based on the estimation of
      the transfer entropy (TE) between insulin and glucose signals. The algorithm has
      been evaluated in silico in adults, adolescents and children for 10 days. Three
      scenarios of initialization to i) zero values, ii) random values and iii) TE
      based values have been comparatively assessed. The results have shown that when
      the TE-based initialization is used, the algorithm achieves faster learning with
      98%, 90% and 73% in the A+B zones of the Control Variability Grid Analysis for
      adults, adolescents and children respectively after five days compared to 95%,
      78%, 41% for random initialization and 93%, 88%, 41% for zero initial values.
      Furthermore, in the case of children, the daily Low Blood Glucose Index reduces
      much faster when the TE-based tuning is applied. The results imply that automatic
      and personalized tuning based on TE reduces the learning period and improves the
      overall performance of the AC algorithm. 

PMID- 24110481
TI  - Needle-free interstitial fluid acquisition using a Lorentz-force actuated jet
      injector.
AB  - The feasibility of a new method of quickly acquiring interstitial fluid (ISF)
      samples using a Lorentz-force actuated needle-free jet injector is demonstrated
      on ex vivo porcine tissue. The jet injector is used to first inject a small
      volume of physiological saline to breach the skin, and the back-drivability of
      the actuator is utilized to create a vacuum in the ampoule and collect ISF.
      Injection and extraction parameters are tested and optimized for minimal acquired
      sample dilution and extracted volume consistency. Using this method, we are able
      to collect a sample that contains up to 3.5% ISF in 3.1 s. 

PMID- 24110482
TI  - Toward a real-time tracking of a medical deformable needle from strain
      measurements.
AB  - Needles used in medical percutaneous procedures are brought to deform because of
      its interactions with inhomogeneous and anisotropic tissues. In this paper, the
      first step of the development of a new generation of tools for assistance in the
      realization of gestures taking into account these deformations are presented. We
      provide a new approach for determining, in "real time" and in 3D, the shape of an
      instrumented needle inserted into a complex tissue by using strain microgauges.
      The knowledge of the real time local deformation from these strain microgauges
      would improve the current navigation systems by considering not only the rigid
      needles but also the flexible ones. Our aim is to reconstruct in real time the
      instrumented needle shape in order to help tracking and steering during a medical
      intervention. 

PMID- 24110483
TI  - Experimental analysis of the performance of an air-powered needle-free liquid jet
      injector.
AB  - An experimental study was performed using a custom-built air-powered needle-free
      injector to investigate the various injector parameters governing the dynamics of
      jet injection. A parametric study using five different nozzle sizes at driver
      pressure ranging from 4 to 8 bar was carried out. The fluid stagnation pressure
      of the liquid jet was determined using a Honeywell force sensor. Performance
      plots as a function of various parameters were constructed. It was determined
      that as the driver pressure increased both the peak and average stagnation
      pressure increased almost linearly within the operating range considered. Varying
      the injection nozzle diameter, whilst keeping the driver pressure constant did
      not have any significant impact on the peak or average stagnation pressure. The
      chamber length was also varied and no significant influence was found on peak or
      average stagnation pressure. 

PMID- 24110484
TI  - Impact of haemodialysis on insulin sensitivity of acute renal failure (ARF)
      patients with sepsis in critical care.
AB  - Critically ill patients often develop renal failure in addition to their primary
      diagnosis. However, the effect and impact of haemodialysis (HD) on insulin
      sensitivity n critically ill patients remains unclear. Specifically, this study
      investigates insulin sensitivity of acute renal failure (ARF) patients with
      sepsis who underwent HD and glycaemic control. Model-based insulin sensitivity
      (SI) profiles were identified for 20 critically ill ARF patients on Specialized
      Relative Insulin Nutrition Titration (SPRINT) glycaemic control during intervals
      onto HD (OFF/ON), and after HD (ON/OFF). Patients exhibited a median -18% (IQR 
      36% to -5% p<0.05) reduction in measured SI after the OFF/ON dialysis transition,
      and a median 9% (IQR -5% to 37%, p<0.05) rise after the ON/OFF transition. Almost
      80% of patients exhibited decreased SI at the OFF/ON interval, and 60% exhibited
      increased SI at the ON/OFF transition. Results indicate that HD commencement has
      significant effect on insulin pharmacokinetics at a cohort and per-patient level.
      These results provide the data to design conclusive studies of HD effects on SI,
      and to inform glycaemic control protocol development and implementation for this
      specific group of critically ill patients with ARF-sepsis. 

PMID- 24110485
TI  - An ensemble rank learning approach for gene prioritization.
AB  - Several different computational approaches have been developed to solve the gene
      prioritization problem. We intend to use the ensemble boosting learning
      techniques to combine variant computational approaches for gene prioritization in
      order to improve the overall performance. In particular we add a heuristic
      weighting function to the Rankboost algorithm according to: 1) the absolute ranks
      generated by the adopted methods for a certain gene, and 2) the ranking
      relationship between all gene-pairs from each prioritization result. We select 13
      known prostate cancer genes in OMIM database as training set and protein coding
      gene data in HGNC database as test set. We adopt the leave-one-out strategy for
      the ensemble rank boosting learning. The experimental results show that our
      ensemble learning approach outperforms the four gene-prioritization methods in
      ToppGene suite in the ranking results of the 13 known genes in terms of mean
      average precision, ROC and AUC measures. 

PMID- 24110486
TI  - A hybrid model for the prediction of mRNA polyadenylation signals.
AB  - The mRNA polyadenylation is the cellular process that adds adenosine tails to
      mature mRNAs. Malfunction of polyadenylation has been implicated in several human
      diseases. In this paper, we proposed a novel feature extraction approach which
      employs the K-gram nucleotide acid pattern, the position weight matrix (PWM) and
      the increment of diversity (ID) to represent the original features. Then
      Principle Component Analysis (PCA) was applied to transform the original features
      into a new feature space where the low-dimensional features were used to train
      the real-coded genetic neural network model. In the experiments, our proposed
      algorithm (GA-BP) can achieve the accuracy about 82.98%, specificity 82.95% and
      sensitivity 83.01% in the specific dataset constructed by Kalkatawi. The results
      demonstrate that GA-BP is a promising algorithm for the prediction of mRNA
      polyadenylation signals. 

PMID- 24110487
TI  - A bio-inspired cooperative algorithm for distributed source localization with
      mobile nodes.
AB  - In this paper we propose an algorithm for distributed optimization in mobile
      nodes. Compared with many published works, an important consideration here is
      that the nodes do not know the cost function beforehand. Instead of decision
      making based on linear combination of the neighbor estimates, the proposed
      algorithm relies on information-rich nodes that are iteratively identified. To
      quickly find these nodes, the algorithm adopts a larger step size during the
      initial iterations. The proposed algorithm can be used in many different
      applications, such as distributed odor source localization and mobile robots.
      Comparative simulation results are presented to support the proposed algorithm. 

PMID- 24110488
TI  - Experimental comparison of classification methods for key kinase identification
      for neurite elongation.
AB  - Kinases in a developing neuron play important roles in elongating a neurite with
      their complex interactions. To elucidate the effect of each kinase on neurite
      elongation and regeneration from a small set of experiments, we applied machine
      learning methods to synthetic datasets based on a biologically feasible model.
      The result showed the ridged partial least squares (RPLS) algorithm performed
      better than other standard algorithms such as naive Bayes classifier, support
      vector machines and random forest classification. This suggests the effectiveness
      of dimension reduction done in RPLS. 

PMID- 24110489
TI  - Compartmental pharmacokinetic modeling of lopinavir in humans.
AB  - BACKGROUND: Lopinavir is a highly potent protease inhibitors commonly used in
      treatment of HIV infection. The drug has a very low bioavailability due to a
      rapid metabolism by cytochrome P450 3A (CYP3A) isoenzyme. We aimed to develop a
      biologically relevant pharmacokinetic model of lopinavir with a description of a
      CYP3A4-mediated first pass metabolism and enterohepatic circulation (EHC).
      METHODS: A theoretical model of lopinavir was developed using the classical
      pharmacokinetic modeling concept. The model consisted of one compartment with
      first-order absorption from gastrointestinal (GI) depot and first-order clearance
      into recycling depot which incorporated into the model structure using ACSLX.
      RESULTS: Lopinavir plasma concentration-time course was successfully simulated
      against a dataset from the literature. The model had an absorption rate constant
      (Ka) of 0.991 h(-1), a reabsorption rate constant (K(reabsorb)) of 0.171 h(-1),
      and a volume of distribution (V/F) of 54.7 L. The 12 hours area under the
      concentration-time curve (AUC0-12h) values from our model simulation compares to
      the experimental data were 0.8141 ug/ml.h and 0.7058 ug/ml.h, respectively.
      Maximum plasma concentration of the drug (Cmax) predicted from our model compare
      to the experimental data were 0.273 ug/ml and 0.442 ug/ml, respectively. While,
      minimum plasma concentration of the drug (C(trough)) predicted from our model
      compare to the experimental data were similar at 0.0015 ug/ml. CONCLUSIONS:
      Modified one compartment with first-order absorption from gastrointestinal (GI)
      depot and first-order clearance into recycling depot describes a pharmacokinetic
      of oral single dose of lopinavir 400 mg. The model can also simulate a
      concentration-time course with a difference dosing and variable which can be used
      for further describing the pharmacology of the drug interaction when combine with
      the other drugs.

PMID- 24110491
TI  - The significance of LPV modeling of a widely used T1DM model.
AB  - The paper investigates the specificity of Linear Parameter Varying (LPV) modeling
      and robust controller design on a widely used Type 1 Diabetes Mellitus model. LPV
      systems can be seen as an extension of linear time invariant systems, which
      allows us to extend some powerful control methodologies to the highly nonlinear
      and uncertain models of the human metabolism. Different LPV models are proposed
      with their own advantages and disadvantages. The possible choices are separately
      analyzed for both controller and observer design perspective. 

PMID- 24110492
TI  - Electrical characteristics of 2D and 3D microelectrodes for high-resolution
      retinal prostheses.
AB  - In order to provide high quality visual information to patients who have
      implanted retinal prosthetic devices, the number of microelectrode should be
      large. As the number of microelectrode is increased, the dimension of the
      microelectrode is decreased, which in turn results in the increased interface
      impedance of microelectrode and decreased dynamic range of injection current. In
      addition, the reduced maximum limit of injection current may not be sufficiently
      large to stimulate the ganglion cells in a retina. In order to improve the trade
      off envelope between number of microelectrode and current injection limit, a 3D
      microelectrode structure can be used as an alternative. From the advancement of
      microfabrication technology, the fabrication of highly-accurate 3D structures
      with small dimensions is possible. This paper presents a first comprehensive
      electrical characterization of 2D and 3D microelectrodes for high-resolution
      retinal prostheses. Microelectrodes which differ in shapes and diameters are
      analyzed. Their interface impedances and charge injection limits are
      quantitatively analyzed. This research can be used to define requirements for
      further retinal prosthetic device research. 

PMID- 24110493
TI  - Visual evoked potential characterization of rabbit animal model for retinal
      prosthesis research.
AB  - Visual evoked potentials (VEP) are used to confirm the function of prosthetic
      devices designed to stimulate retinas with damaged photoreceptors in vivo. In
      this work, we focus on methods and experimental consideration for recording
      visual evoked potential in rabbit models and assesses the use for retinal
      prosthesis research. We compare both invasive and noninvasive methods for
      recording VEPs, the response of the rabbit retina to various light wavelengths
      and intensities, focal vs. full field stimulation, and the effect of light
      bleaching on the retinal response. 

PMID- 24110494
TI  - Effect of saccades in tongue electrotactile stimulation for vision substitution
      applications.
AB  - The visual substitution paradigm aims to facilitate the life of blind people.
      Generally one uses electro-stimulating devices where electrodes are arranged into
      arrays to stimulate the skin or the tongue mucosa to send signals of visual type
      to the subjects. When an electro-stimulation signal is applied continuously (e.g.
      when static visual scenes are displayed for a long period of time), the receptors
      of the affected region can get saturated and the patient may lose the displayed
      information. We propose here some mechanisms that ameliorate the quality of
      perception of the electro-stimulation information. The electrical signal is
      encoded as 2D scenes projected onto the tongue via a Tongue Display Unit, i.e. an
      electro-tactile stimulator formed by a 12*12 matrix of electrodes. We propose to
      apply stochastic saccades on this signal. Our assumption is that this eye
      inspired mechanism should make the visual substitution more efficient (by
      improving the perception) because of the reduction of the tactile receptors
      saturation. The influence of saccades was evaluated by a series of experiments.
      Results revealed a benefit on the persistence of perception due to saccades. This
      work helps to prevent the saturation of receptors on the tongue. Therefore
      increasing the quality of vision by the way of the electro-stimulation. It allows
      new enhancement features to retinal prosthesis devices which suffer from the same
      phenomenon. 

PMID- 24110495
TI  - Can passive mobilization provide clinically-relevant brain stimulation? A pilot
      EEG and NIRS study on healthy subjects.
AB  - Lower limb rehabilitation is a fundamental part of post-acute care in
      neurological disease. Early commencement of active workout is often prevented by
      paresis, thus physical treatment may be delayed until patients regain some
      voluntary command of their muscles. Passive mobilization of the affected joints
      is mostly delivered in order to safeguard tissue properties and shun circulatory
      problems. The present paper investigates the potential role of early passive
      motion in stimulating cortical areas of the brain devoted to the control of the
      lower limb. An electro-mechanical mobilizer for the ankle joint (Toe-Up!) was
      implemented utilizing specially-designed shape-memory-alloy-based actuators. This
      device was constructed to be usable by bedridden subjects. Besides, the slowness
      and gentleness of the imparted motion, make it suitable for patients in a very
      early stage of their recovery. The mobilizer underwent technical checks to
      confirm reliability and passed the required safety tests for electric biomedical
      devices. Four healthy volunteers took part in the pre-clinical phase of the
      study. The protocol consisted in measuring of brain activity by EEG and NIRS in
      four different conditions: rest, active dorsiflexion of the ankle, passive
      mobilization of the ankle, and assisted motion of the same joint. The acquired
      data were processed to obtain maps of cortical activation, which were then
      compared. The measurements collected so far show that there is a similar pattern
      of activity between active and passive/assisted particularly in the contralateral
      premotor areas. This result, albeit based on very few observations, might suggest
      that passive motion provides somatosensory afferences that are processed in a
      similar manner as for voluntary control. Should this evidence be confirmed by
      further trials on healthy individuals and neurological patients, it could form a
      basis for a clinical use of early passive exercise in supporting central
      functional recovery. 

PMID- 24110496
TI  - Bedside assessment of residual functional activation in minimally conscious state
      using NIRS and general linear models.
AB  - Near Infrared Spectroscopy (NIRS) was employed for the detection of possible
      residual functional activations in two patients in minimally conscious state. An
      "ad hoc" protocol for somatosensory and motor stimulations was created and
      administered to the patients, synchronously to NIRS recordings. One healthy
      subject was also assessed with the same task for comparison. Results from the
      healthy subject globally agree with the literature. Moreover, we could obtain
      significant results from the patients data. Indeed, in one patient, the NIRS
      channels showing activation completely correspond to regions of residual cortex
      underneath. In the second patient, though, together with possible residual intact
      cortex insulae, some channels match large cystic formations, with fluid
      gathering. 

PMID- 24110497
TI  - Auditory mismatch negativity in cochlear implant users: a window to spectral
      discrimination.
AB  - A cochlear implant (CI) can partially restore hearing in patients with severe to
      profound sensorineural hearing loss. However, the large outcome variability in CI
      users prompts the need for more objective measures of speech perception
      performance. Electrophysiological metrics of CI performance may be an important
      tool for audiologists in the assessment of hearing rehabilitation. Utilizing
      electroencephalography (EEG), it may be possible to evaluate speech perception
      correlates such as spectral discrimination. The mismatch negativity (MMN) of 10
      CI subjects was recorded for stimuli containing different spectral densities. The
      neural spectral discrimination threshold, estimated by the MMN responses, showed
      a significant correlation with the behavioral spectral discrimination threshold
      measured in each subject. Results suggest that the MMN can be potentially used to
      obtain an objective estimate of spectral discrimination abilities in CI users. 

PMID- 24110498
TI  - A microprocessor-based multichannel subsensory stochastic resonance electrical
      stimulator.
AB  - Stochastic resonance electrical stimulation is a novel intervention which
      provides potential benefits for improving postural control ability in the
      elderly, those with diabetic neuropathy, and stroke patients. In this paper, a
      microprocessor-based subsensory white noise electrical stimulator for the
      applications of stochastic resonance stimulation is developed. The proposed
      stimulator provides four independent programmable stimulation channels with
      constant-current output, possesses linear voltage-to-current relationship, and
      has two types of stimulation modes, pulse amplitude and width modulation. 

PMID- 24110499
TI  - Embracing the irregular: a patient-specific image processing strategy for visual
      prostheses.
AB  - We propose a stimulation strategy for retinal prostheses that makes use of
      irregular shapes of elicited phosphenes. It is patient specific and thus relies
      on prior psychophysical measurements. Visual perceptions are stored in a
      phosphene map that relates stimulation parameters to the visual stimulus
      elicited. Based on this map, stimulation parameters are chosen in such a way that
      the edges of the target image are optimally represented through the shape of the
      phosphene. In a psychophysical pilot study, we compare this approach to one in
      which we choose phosphenes to match the brightness of the target image. We find
      that participants perform similarly well with both strategies overall. However,
      the results indicate that each strategy may have advantages for different
      stimulus sizes. Both of the proposed strategies are novel in using only
      previously recorded phosphenes rather than a model based on idealized assumptions
      about the relationship between stimulation parameters and phosphene properties. 

PMID- 24110500
TI  - Safety assessment of semichronic suprachoroidal electrical stimulation to rabbit
      retina.
AB  - Confirming safety of chronic electrical stimulation is of prime importance for
      the practical use of visual prostheses. Here we applied electrical stimulation to
      eyes of freely-moving rabbits eight hour per day for one month. Examinations
      including fundus photo, optical coherence tomography (OCT), electrically evoked
      potentials (EEPs) were performed before and after one-month stimulation to detect
      tissue damage. No adverse effect caused by electrical stimulation was observed in
      electrophysiological and histological evaluation. We also found that there was no
      sign of morphological and electrochemical degradation of stimulating electrodes. 

PMID- 24110501
TI  - Electrical stimulation device as possible treatment for nocturnal bruxism:
      preliminary results.
AB  - Nocturnal bruxism (NB) is a temporomandibular disorder characterized by an
      excessive clenching and involuntary parafunctional grinding of the teeth during
      sleep. It can cause dental damage and irreversible temporomandibular joint
      dysfunction. We designed a device that generates electrical stimulation on
      inhibitory sensory afferents when an EMG signal is measured. This stimulation was
      applied to the right mental nerve to produce a decrease in the contraction
      intensity of the mandibular elevation muscles. To measure the intensity of
      contraction, electromyographic (EMG) signal of the left temporalis anterior (LTa)
      muscle was used. The results showed that, on average, the percentage decrease in
      the bruxist group was 30.53% and for the control group was 28.91%. These results
      indicate that the device implemented generates an important decrease in the
      muscle contractile activity. Therefore, the device could be useful as a possible
      treatment to decrease nocturnal bruxism. 

PMID- 24110502
TI  - Development of a novel hearing-aid for the profoundly deaf using bone-conducted
      ultrasonic perception: evaluation of transposed modulation.
AB  - Bone-conducted ultrasound (BCU) is perceived even by the profoundly sensorineural
      deaf. A novel hearing aid using the perception of amplitude-modulated BCU (BCU
      hearing aid: BCUHA) has been developed. However, there is room for improvement
      particularly in terms of articulation and sound quality. BCU speech is
      accompanied by a strong high-pitched tone and contain some distortion. In this
      study, transposed modulation, that can be expected to reduce the high-pitched
      tone was newly employed as a modulation method in the BCUHA, and its resulting
      articulation, intelligibility and sound quality were evaluated. The results
      showed that transposed modulation showed nearly equal articulation and
      intelligibility scores to and better sound quality than the existing method, DSB
      TC modulation. These results provide useful information for further development
      of the BCUHA. 

PMID- 24110503
TI  - The precise adjustment of coil location for transcranial magnetic stimulation
      during dynamic motion.
AB  - Transcranial magnetic stimulation (TMS) to the cerebral cortex is a major in
      vitro technique that is used in the field of neurophysiology. The magnitude of
      the motor-evoked potentials (MEP) that are elicited by TMS to the primary motor
      cortex reflect the excitability of the corticospinal pathway. MEPs are very
      sensitive to the scalp location of the stimulus coil, especially when
      corticospinal excitability is recorded during walking or other dynamic motions.
      In this study, we created a coil navigational system that consisted of three
      dimensional motion analysis cameras, rigid bodies on the head and coil, and
      programming software. In order to evaluate the feasibility of the use of our
      system, pseudo TMS was applied during treadmill walking with or without the
      navigational system. As a result, we found that the variances due to coil
      location and/or distance from the target site were reduced with our system. This
      technique enabled us to realize high precision and accuracy in coil placement,
      even during dynamic motion. 

PMID- 24110504
TI  - Study on performance evaluation system for transcranial magnetic stimulation
      devices.
AB  - Transcranial magnetic stimulation devices have been widely used for clinic and
      research purposes and their performance such as stimulation strength, depth and
      focality are of great concern from various studies. However, there is no specific
      evaluation index nowadays. TMS devices could only be appraised qualitatively with
      accurate parameters, thus, a preliminary evaluation work for TMS devices is
      proposed in this paper. Practical indexes are proposed in order to give a clear
      image of the TMS device performance. This work may provide a design guideline for
      TMS device, performance evaluation and comparison as well. 

PMID- 24110505
TI  - Coil positioning system for repetitive transcranial magnetic stimulation
      treatment by ToF camera ego-motion.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method for
      treating various neurological and psychiatric disorders. With the growing demands
      of neuropathic pain patients and their increasing numbers, rTMS treatment tools
      are becoming more necessary. rTMS uses electromagnetic induction to induce weak
      electric currents by rapidly changing the magnetic field. Targeting the electric
      current to a specific part of the brain is one treatment for pain relief. This
      paper focuses on treatment for neuropathic pain caused by a lesion or disease of
      the central or peripheral nervous system, including stroke, trauma, or surgery.
      However, the current style of rTMS treatment is still developing and is so
      technically specialized that only a limited number of hospitals and only a
      handful of specialists can provide this therapy. The existing rTMS systems use an
      optical markerbased 3D sensing technique that positions the stimulation coil to
      target the small region of interest in the brain through coregistration with pre
      scanned MRI data. This system requires the patient to be immobilized on a bed.
      The optical markers for 3D sensing are placed on the patient's head to maintain
      accurate positioning. We propose a constraints-free, markerless rTMS system,
      which employs ego-motion, a computation technique to estimate relative 3D motion
      of a camera to what the camera sees. We use a ToF sensor as a camera, which is
      capable of capturing shape information from a single viewpoint instantly. The
      markerless target spot is based on the shape features of the patient's face. This
      paper shows the process of a prototype system and its potential for achieving an
      easy-to-handle system framework.

PMID- 24110506
TI  - Effects of low amplitude pulsed radiofrequency stimulation with different
      waveform in rats for neuropathic pain.
AB  - Pulsed-radiofrequency (PRF) electrical stimulation has been widely used for
      chronic pain treatment. It has been demonstrated with advantages of low
      temperature over traditional continuous radiofrequency (CRF) lesions with higher
      amplitude and mono polar electrode to treat pain in clinics (frequency 500 KHz,
      Pulse duration 20 msec, Amplitude 45 V, Treatment 2 min). We compare the effects
      of different pulse waveforms and PRF parameters (Pulse duration 25 ms, Treatment
      duration 5 min, low amplitude of 2.5/1.25 V) with a miniature bi-polar electrode
      on Dorsal root ganglion (DRG). The pain relief effect due to PRF is evaluated by
      using Von Frey method for the pain threshold index based on behavior response to
      mechanical stimulus of various strengths. Experimental results of Von Frey Score
      show that the sinusoidal group has higher responses than the square wave one.
      Both fast and secondary expressed proteins of c-fos and pp38 are measured from
      spinal cord tissue sectioning slides to characterize the pain associated
      inflammatory responses and their responses due to PRF stimulation. 

PMID- 24110507
TI  - Offline decoding of upper limb muscle synergies from EEG slow cortical
      potentials.
AB  - Muscle synergies are thought to be the building blocks used by the central
      nervous system to control the underdetermined problem of muscles activation.
      Decoding these synergies from EEG could provide useful tools for BCI-controlled
      orthotic devices. In this paper, we assess the possibility of decoding muscle
      synergies from EEG slow cortical potentials in two healthy subjects and two
      stroke patients performing a center-out reaching task. We were able to
      successfully decode the extracted muscle synergies in both healthy subject and
      one patient. 

PMID- 24110508
TI  - Modeling open-loop stability of a human arm driven by a functional electrical
      stimulation neuroprosthesis.
AB  - Functional electrical stimulation (FES) can be used to restore movement control
      following paralysis. For complex multijoint systems, it is becoming increasingly
      apparent that closed-loop controllers are needed. Designing a closed-loop control
      system is easiest when the open-loop system is stable. In this study we developed
      a computational model to assess the open-loop stability of FES-control systems.
      We used the model to examine the open-loop stability of the human arm throughout
      its reachable workspace. For each simulated position of the hand we examined the
      stability of the arm, assuming that a minimal pattern of muscle activation was
      used to support the arm against gravity. Only muscles available to an existing
      FES user were considered. We found that with this reduced muscle set, the
      stability of the arm was severely compromised. We also demonstrated that muscle
      co-contraction can be an effective method to improve the stability for many
      postures. 

PMID- 24110509
TI  - Using speech for mode selection in control of multifunctional myoelectric
      prostheses.
AB  - Electromyogram (EMG) recorded from residual muscles of limbs is considered as
      suitable control information for motorized prostheses. However, in case of high
      level amputations, the residual muscles are usually limited, which may not
      provide enough EMG for flexible control of myoelectric prostheses with multiple
      degrees of freedom of movements. Here, we proposed a control strategy, where the
      speech signals were used as additional information and combined with the EMG
      signals to realize more flexible control of multifunctional prostheses. By
      replacing the traditional "sequential mode-switching (joint-switching)", the
      speech signals were used to select a mode (joint) of the prosthetic arm, and then
      the EMG signals were applied to determine a motion class involved in the selected
      joint and to execute the motion. Preliminary results from three able-bodied
      subjects and one transhumeral amputee demonstrated the proposed strategy could
      achieve a high mode-selection rate and enhance the operation efficiency,
      suggesting the strategy may improve the control performance of commercial
      myoelectric prostheses. 

PMID- 24110510
TI  - Design and validation of a neuroprosthesis for the treatment of upper limb
      tremor.
AB  - Pathological tremor is the most prevalent movement disorder. In spite of the
      existence of various treatments for it, tremor poses a functional problem to a
      large proportion of patients. This paper presents the design and implementation
      of a novel neuroprosthesis for tremor management. The paper starts by reviewing a
      series of design criteria that were established after analyzing users needs and
      the expected functionality of the system. Then, it summarizes the design of the
      neuroprosthesis, which was built to meet the criteria defined previously.
      Experimental results with a representative group of 12 patients show that the
      neuroprosthesis provided significant (p < 0.001) and systematic tremor
      attenuation (in average 52.33 +/- 25.48 %), and encourage its functional
      evaluation as a potential new treatment for tremor in a large cohort of patients.

PMID- 24110511
TI  - An implantable wireless system for muscle afferent recording from the sciatic
      nerve during functional electrical stimulation.
AB  - An implantable wireless system was developed for recording muscle afferent
      activity and stimulating peripheral nerves with cuff electrodes. The proposed
      system was fabricated into the nerve cuff electrode, neural amplifier, neural
      stimulator, and wireless communication system with battery power. The nerve cuff
      electrode and neural amplifier were designed to improve the signal-to
      interference ratio and signal-to-noise ratio. The wireless communication system
      was designed based on the medical implant communication service regulations to be
      suitable for implantation. The main function of this system was to extract muscle
      afferent activity from peripheral nerve during functional electrical stimulation.
      The cuff electrodes were chronically implanted on the sciatic nerve for recording
      and on the tibial and peroneal nerves for stimulation. When the extension and
      flexion movements of ankle joint were elicited from alternative electrical
      stimuli, the corresponding neural signals and ankle angles were recorded
      simultaneously. The muscle afferent activity was then extracted from the recorded
      neural signal through a simple blanking process. The experimental results showed
      that the ankle movements could be detected from the extracted muscle afferent
      activity. 

PMID- 24110512
TI  - Spatially distributed sequential stimulation reduces muscle fatigue during
      neuromuscular electrical stimulation.
AB  - A critical limitation with neuromuscular electrical stimulation (NMES) approach
      is the rapid onset of muscle fatigue during repeated contractions, which results
      in the muscle force decay and slowing of muscle contractile properties. In our
      previous study, we demonstrated that spatially distributed sequential stimulation
      (SDSS) show a drastically greater fatigue-reducing ability compared to a
      conventional, single active electrode stimulation (SES) with an individual with
      spinal cord injury when applied for plantar flexors. The purpose of the present
      study is to explore the fatigue-reducing ability of SDSS for major lower limb
      muscle groups in the able-bodied population as well as individuals with spinal
      cord injury (SCI). SDSS was delivered through four active electrodes applied to
      the muscle of interest, sending a stimulation pulse to each electrode one after
      another with 90 degrees  phase shift between successive electrodes. For
      comparison, SES was delivered through one active electrode. For both modes of
      stimulation, the resultant frequency to the muscle as a whole was 40 Hz. Using
      corresponding protocols for the fatiguing stimulation, we demonstrated the
      fatigue-reducing ability of SDSS by higher fatigue indices as compared with
      single active electrode setup for major leg muscles in both subject groups. The
      present work verifies and extends reported findings on the effectiveness of using
      spatially distributed sequential stimulation in the leg muscles to reduce muscle
      fatigue. Application of this technique can improve the usefulness of NMES during
      functional movements in the clinical setup. 

PMID- 24110513
TI  - Temporal muscle activation assessment by ultrasound imaging during flexor
      withdrawal reflex and voluntary contraction.
AB  - Activating flexor reflexes by electrical stimulation has been used as a mechanism
      to initiate the swing phase or to enhance it for spinal cord injured patients.
      However, it is necessary to know their contraction dynamics in order to
      artificially induce them at the right moment of a walking cycle. This requires
      understanding the temporal activation pattern of both surface and deep muscles
      simultaneously. This study aimed at developing a system to measure and analyze
      the temporal activation of both surface and deep muscles during voluntary
      contraction and flexor reflexes (also called withdrawal reflexes) using
      ultrasound imaging. A set of experiments were done to verify the validity of the
      system, while exploring the temporal pattern of muscle activation during flexor
      reflexes. As a result, we were able to quantify the surface and deep muscle
      activity by measuring the muscle thickness, pennation angle and long-axis
      displacement, from the ultrasound images. 

PMID- 24110514
TI  - Long term stability of surface EMG pattern classification for prosthetic control.
AB  - Long-term functioning of a hand prosthesis is crucial for its acceptance by
      patients with upper limb deficit. In this study the reliability over days of the
      performance of pattern classification approaches based on surface
      electromyography (sEMG) signal for the control of upper limb prostheses was
      investigated. Recordings of sEMG from the forearm muscles were obtained across
      five consecutive days from five healthy subjects. It was demonstrated that the
      classification performance decreased monotonically on average by 4.1% per day. It
      was also found that the accumulated error was confined to three of the eight
      movement classes investigated. This contribution gives insight on the long term
      behavior of pattern classification, which is crucial for commercial viability. 

PMID- 24110515
TI  - Pudendal neuromodulation with a closed-loop control strategy to improve bladder
      functions in the animal study.
AB  - The aim of this study was to develop a new closed-loop control strategy for
      improving bladder emptying and verify its performance in animal experiments. Two
      channel outputs of electrical currents triggered by intravesical pressure (IVP)
      feedback signals were set to automatically regulate the rat's pudendal nerve for
      selective nerve stimulation and blocking. Under this experimental design, a
      series of in-vivo animal experiments were conducted on anesthetized rats. Our
      results showed that the IVP-feedback control strategy for dual-channel pudendal
      neuromodulation performed well in animal experiments and could be utilized to
      selectively stimulate and block the pudendal nerve to augment bladder contraction
      and restore external urethral sphincter (EUS) bursting activity to simultaneously
      improve bladder emptying. This study demonstrates the feasibility of the IVP
      based feedback-control strategy with animal experiments, and the results could
      provide a basis for developing a sophisticated neural prosthesis for restoring
      bladder function in clinical use or the relative neurophysiological study. 

PMID- 24110516
TI  - Real-time comparison of conventional direct control and pattern recognition
      myoelectric control in a two-dimensional Fitts' law style test.
AB  - Few studies have directly compared real-time control performance of pattern
      recognition to direct control for the next generation of myoelectric controlled
      upper limb prostheses. Many different implementations of pattern recognition
      control have been proposed, with minor differentiations in the feature sets and
      classifiers. An objective and generalizable evaluation tool quantifying the
      control performance, other than classification accuracy, is needed. This paper
      used the implementation of such a tool through the design of a target acquisition
      test, similar to a Fitts' law test, relating movement time of the target
      acquisition to the difficulty of the target, for a given control strategy.
      Performance metrics such as throughput (bits/sec), completion rate (%) and path
      efficiency (%) allow for a complete evaluation of the described strategies. We
      compared direct control and pattern recognition control with the proposed test
      and found that 1) the test was valid for control system evaluation by following
      Fitts' law with high coefficients of determination for both types of control and
      2) that pattern recognition significantly outperformed direct control in
      throughput with similar completion rates and path efficiencies. In this
      framework, the present pilot study supports pattern recognition as a promising
      strategy and forms a basis for the development of a general and objective tool
      for the performance evaluation of upper limb control strategies. 

PMID- 24110517
TI  - Compensation for injury potential by electrical stimulation after acute spinal
      cord injury in rat.
AB  - Injury potential, a direct current potential difference between normal section
      and the site of injury, is a significant index of spinal cord injury. However,
      its importance has been ignored in the studies of spinal cord electrophysiology
      and electrical stimulation (ES). In this paper, compensation for injury potential
      is used as a criterion to adjust the intensity of stimulation. Injury potential
      is modulated to slightly larger than 0 mV for 15, 30 and 45 minutes immediately
      after injury by placing the anodes at the site of injury and the cathodes at the
      rostral and caudal section. Injury potentials of all rats were recorded for
      statistical analysis. Results show that the injury potentials acquired after ES
      are higher than those measured from rats without stimulation and much lower than
      the initial amplitude. It is also observed that the stimulating voltage to keep
      injury potential be 0 remain the same. This phenomenon suggests that repair of
      membrane might occur during the period of stimulation. It is also suggested that
      a constant voltage stimulation can be applied to compensate for injury potential.

PMID- 24110518
TI  - Shared control strategies for human-machine interface in an intelligent
      wheelchair.
AB  - In this paper, we introduce a shared control mechanism for an intelligent
      wheelchair designed to support people with mobility impairments, who also have
      visual, upper limb, or cognitive impairment. The method is designed to allow
      users to be involved in the movement as much as possible, while still providing
      the assistance needed to achieve the goal safely. The data collected through URG
      04LX and user interface are analyzed to determine whether the desired action is
      safe to perform. The system then decides to provide assistance or to allow the
      user input to control the wheelchair. The experiment results indicate that the
      method performs effectively with high satisfaction. 

PMID- 24110519
TI  - The advancement of an obstacle avoidance Bayesian neural network for an
      intelligent wheelchair.
AB  - In this paper, an advanced obstacle avoidance system is developed for an
      intelligent wheelchair designed to support people with mobility impairments who
      also have visual, upper limb, or cognitive impairment. To avoid obstacles,
      immediate environment information is continuously updated with range data sampled
      by an on-board laser range finder URG-04LX. Then, the data is transformed to find
      the relevant information to the navigating process before being presented to a
      trained obstacle avoidance neural network which is optimized under the
      supervision of a Bayesian framework to find its structure and weight values. The
      experiment results showed that this method allows the wheelchair to avoid
      collisions while simultaneously navigating through an unknown environment in real
      time. More importantly, this new approach significantly enhances the performance
      of the system to pass narrow openings such as door passing. 

PMID- 24110520
TI  - Half-Against-Half structure in classification of benthic macroinvertebrate
      images.
AB  - Benthic macroinvertebrates play a key role when water quality assessments are
      made. Benthic macroinvertebrates are difficult to identify and their
      identification need special expertise. Furthermore, manual identification is slow
      and expensive process. This paper concerns benthic macroinverte-brate
      classification when Half-Against-Half (HAH) structure was applied to Support
      Vector Machine (SVM), Linear Discriminant Analysis (LDA), Quadratic Discriminant
      Analysis (QDA) and Minimum Mahalanobis Distance Classifier (MMDC) classifiers.
      Especially, LDA, QDA and MMDC classifiers were for first time applied with HAH
      structure to benthic macroinvertebrate classification. We performed thorough
      experiments altogether with ten methods. In the case of HAH-SVM we managed to
      improve classification results from the earlier research by using a different
      approach to class division problem. We obtained 96.1% classification accuracy
      with Radial Basis Function (RBF) kernel. Moreover, new variants of LDA, QDA and
      MMDC classification methods achieved 89.5% and 91.6% classification accuracies
      which can be considered as a good result in such a difficult classification task.

PMID- 24110521
TI  - Multiobjective evolutionary optimization for tumor segmentation of breast
      ultrasound images.
AB  - This paper proposes a robust multiobjective evolutionary algorithm (MOEA) to
      optimize parameters of tumor segmentation for ultrasound breast images. The
      proposed algorithm employs efficient schemes for reinforcing proximity to Pareto
      optimal and diversity of solutions. They are designed to solve multiobjective
      problems for segmentation accuracy and speed. First objective is evaluated by
      difference between the segmented outline and ground truth. Second objective is
      evaluated by elapsed time during segmentation process. The experimental results
      show the effectiveness of the proposed algorithm compared with conventional MOEA
      from the viewpoint of proximity to the Pareto-optimal front (improved by 16.4%
      and 12.4%). Moreover, segmentation results of proposed algorithm describe faster
      segmentation speed (1.97 second) and higher accuracy (8% Jaccard). 

PMID- 24110522
TI  - Exploiting gastrointestinal anatomy for organ classification in capsule endoscopy
      using locality preserving projections.
AB  - Capsule Endoscopy is a technique designed to wirelessly image the small intestine
      within the gastrointestinal (GI) tract. Its main drawback is the vast amount of
      images it generates per patient, necessitating long screening sessions by the
      clinician. Previous studies have proposed to partially facilitate this process by
      automatically segmenting the GI tract into its constituent organs, thus
      identifying the region of interest. In this work, we propose to exploit the
      anatomical structure of the GI tract when carrying out dimensionality reduction
      on visual feature vectors that describe the capsule images. To this end, we
      suggest a novel adaptation of a technique called Locality Preserving Projections,
      and results show that this achieves an improved performance in organ
      classification and segmentation, at no additional computational or memory cost. 

PMID- 24110523
TI  - Automation of ROI extraction in hyperspectral breast images.
AB  - The extraction of regions-of-interest (ROIs) in hyperspectral images of breast
      cancer specimens is currently carried out manually or by visual inspection. In
      order to address the labor-intensive and time-consuming process of the manual
      extraction of ROIs in hyperspectral images, an algorithm is developed in this
      paper to automate the extraction process. This is achieved by using a contrast
      module and a homogeneity module to duplicate the same manual or visual steps that
      an expert goes through in order to extract ROIs. The success of the automated
      process is determined by comparing the classification rates of the automated
      approach with the manual approach in terms of the ability to separate cancer
      cases from normal cases. 

PMID- 24110524
TI  - Liver tumor detection and segmentation using kernel-based Extreme Learning
      Machine.
AB  - This paper presents an approach to detection and segmentation of liver tumors in
      3D computed tomography (CT) images. The automatic detection of tumor can be
      formulized as novelty detection or two-class classification issue. The method can
      also be used for tumor segmentation, where each voxel is to be assigned with a
      correct label, either a tumor class or nontumor class. A voxel is represented
      with a rich feature vector that distinguishes itself from voxels in different
      classes. A fast learning algorithm Extreme Learning Machine (ELM) is trained as a
      voxel classifier. In automatic liver tumor detection, we propose and show that
      ELM can be trained as a one-class classifier with only healthy liver samples in
      training. It results in a method of tumor detection based on novelty detection.
      We compare it with two-class ELM. To extract the boundary of a tumor, we adopt
      the semi-automatic approach by randomly selecting samples in 3D space within a
      limited region of interest (ROI) for classifier training. Our approach is
      validated on a group of patients' CT data and the experiment shows good detection
      and encouraging segmentation results. 

PMID- 24110525
TI  - Robust classification of DNA damage patterns in single cell gel electrophoresis.
AB  - Single cell gel electrophoresis, also known as comet assay, has been widely used
      for assessing the effect of genotoxicity and detecting DNA damage of individual
      eukaryotic cells. There exist established imaging techniques for cometassay
      analysis, but these platforms have limitations such as required user
      interventions, low throughput, and weakness to noise caused by incomplete dyeing
      of fluorescent materials and other experimental errors. To resolve these, we
      propose a novel procedure for analyzing comet assay images, which considers
      various DNA damage patterns and classifies them in a robust manner. We tested our
      approach with twenty golden data sets containing over 300 comets and achieved
      satisfactory classification accuracy. 

PMID- 24110526
TI  - Automated Down syndrome detection using facial photographs.
AB  - Down syndrome, the most common single cause of human birth defects, produces
      alterations in physical growth and mental retardation; its early detection is
      crucial. Children with Down syndrome generally have distinctive facial
      characteristics, which brings an opportunity for the computer-aided diagnosis of
      Down syndrome using photographs of patients. In this study, we propose a novel
      strategy based on machine learning techniques to detect Down syndrome
      automatically. A modified constrained local model is used to locate facial
      landmarks. Then geometric features and texture features based on local binary
      patterns are extracted around each landmark. Finally, Down syndrome is detected
      using a variety of classifiers. The best performance achieved 94.6% accuracy,
      93.3% precision and 95.5% recall by using support vector machine with radial
      basis function kernel. The results indicate that our method could assist in Down
      syndrome screening effectively in a simple, non-invasive way. 

PMID- 24110527
TI  - On the combination of wavelet and curvelet for feature extraction to classify
      lung cancer on chest radiographs.
AB  - This paper investigates the combination of multiresolution methods for feature
      extraction for lung cancer. The focus is on the impact of combining wavelet and
      curvelet on the accuracy of the disease diagnosis. The paper investigates feature
      extraction with two different levels of wavelet, two different wavelet functions
      and the combination of wavelet and curvelet to obtain a high classification rate.
      The findings suggest the potential of combining different multiresolution methods
      in achieving high accuracy rates. 

PMID- 24110529
TI  - Application of fuzzy skeletonization ot quantitatively assess trabecular bone
      micro-architecture.
AB  - Adult bone diseases, especially osteoporosis, lead to increased risk of fracture
      associated with substantial morbidity, mortality, and financial costs.
      Clinically, osteoporosis is defined by low bone mineral density; however,
      increasing evidence suggests that the micro-architectural quality of trabecular
      bone (TB) is an important determinant of bone strength and fracture risk.
      Skeletonization plays an important role providing a compact representation of TB
      network that allows computation of several quantitative parameters relating to TB
      micro-architecture. Literature of three-dimensional skeletonization is quite
      matured for binary digital objects. However, the challenges of skeletonization
      for fuzzy objects are mostly unanswered. Here, an algorithm for fuzzy
      skeletonization is presented using fuzzy grassfire propagation and a branch-level
      noise pruning strategy and, finally, its application to TB micro-architectural
      assessment is investigated. Specifically, the fuzzy skeletonization algorithm is
      applied to compute TB plateness, plate/rod ratio, thickness, and spacing.
      Finally, the effectiveness of these measures to predict experimental bone
      strength is investigated on twelve cadaveric specimens and the results are
      encouraging with the R(2) value of linear correlation with bone strength being as
      high as 0.93, 0.88, 0.85 and 0.86, respectively. 

PMID- 24110530
TI  - Quantitative analysis of lymphocytes morphology and motion in intravital
      microscopic images.
AB  - Studying the morphology and interior movement of lymphocytes in intravital
      microscopic images is essential to understanding and treating various biological
      processes and pathological situations. A method combing features of shape,
      deformation, and intracellular motion for quantitatively characterizing the
      dynamic behavior of a single lymphocyte is proposed in this paper. The method is
      tested on a set of image sequences of lymphocytes obtained from the peripheral
      blood of mice undergoing skin transplantation using a phase contrast microscope.
      Experimental results coincide with the clinical observation and pathological
      analysis, demonstrating that the extracted cell morphology and motion features
      can provide new insights into the relationship between the dynamic behavior of
      lymphocytes and the occurrence of graft rejection. 

PMID- 24110531
TI  - Smartphones as image processing systems for prosthetic vision.
AB  - The feasibility of implants for prosthetic vision has been demonstrated by
      research and commercial organizations. In most devices, an essential forerunner
      to the internal stimulation circuit is an external electronics solution for
      capturing, processing and relaying image information as well as extracting useful
      features from the scene surrounding the patient. The capabilities and multitude
      of image processing algorithms that can be performed by the device in real-time
      plays a major part in the final quality of the prosthetic vision. It is therefore
      optimal to use powerful hardware yet to avoid bulky, straining solutions. Recent
      publications have reported of portable single-board computers fast enough for
      computationally intensive image processing. Following the rapid evolution of
      commercial, ultra-portable ARM (Advanced RISC machine) mobile devices, the
      authors investigated the feasibility of modern smartphones running complex face
      detection as external processing devices for vision implants. The role of
      dedicated graphics processors in speeding up computation was evaluated while
      performing a demanding noise reduction algorithm (image denoising). The time
      required for face detection was found to decrease by 95% from 2.5 year old to
      recent devices. In denoising, graphics acceleration played a major role, speeding
      up denoising by a factor of 18. These results demonstrate that the technology has
      matured sufficiently to be considered as a valid external electronics platform
      for visual prosthetic research. 

PMID- 24110532
TI  - A new quantitative approach for estimating bone cell connections from nano-CT
      images.
AB  - Recent works highlighted the crucial role of the osteocyte system in bone
      fragility. The number of canaliculi of osteocyte lacuna (Lc.NCa) is an important
      parameter that reflects the functionality of bone tissue, but rarely reported due
      to the limitations of current microscopy techniques, and only assessed from 2D
      histology sections. Previously, we showed the Synchrotron Radiation
      nanotomography (SR-nanoCT) is a promising technique to image the 3D lacunar
      canalicular network. Here we present, for the first time, an automatic method to
      quantify the connectivity of bone cells in 3D. After segmentation, our method
      first separates and labels each lacuna in the network. Then, by creating a
      bounding surface around lacuna, the Lc.NCa is calculated through estimating 3D
      topological parameters. The proposed method was successfully applied to a 3D SR
      nanoCT image of cortical femoral bone. Statistical results on 165 lacunae are
      reported, showing a mean of 51, which is consistent with the literature. 

PMID- 24110533
TI  - Automated detection of malaria in Giemsa-stained thin blood smears.
AB  - The current gold standard of malaria diagnosis is the manual, microscopy-based
      analysis of Giemsa-stained blood smears, which is a time-consuming process
      requiring skilled technicians. This paper presents an algorithm that identifies
      and counts red blood cells (RBCs) as well as stained parasites in order to
      perform a parasitaemia calculation. Morphological operations and histogram-based
      thresholding are used to extract the red blood cells. Boundary curvature
      calculations and Delaunay triangulation are used to split clumped red blood
      cells. The stained parasites are classified using a Bayesian classifier with
      their RGB pixel values as features. The results show 98.5% sensitivity and 97.2%
      specificity for detecting infected red blood cells. 

PMID- 24110534
TI  - Model-based segmentation of the middle phalanx in digital radiographic images of
      the hand.
AB  - We present techniques for segmenting the middle phalanx of the middle finger in
      digital radiographic images using deformable models and active shape models
      (ASMs). The result of segmentation may be used in the estimation of bone mineral
      density which in turn may be used in the diagnosis of osteoporosis. A technique
      for minimizing user dependence is described. The segmentation accuracy of the two
      methods is assessed by comparing contours produced by the algorithms to those
      produced by manual segmentation, using the Hausdorff distance measure. The ASM
      technique produces more accurate segmentation. 

PMID- 24110535
TI  - Quantitative measures of facial expression for patients with head and neck
      cancer.
AB  - In addition to changes in facial morphology, head and neck cancer treatment can
      impact the facial expression. Quantification of changes in facial expression,
      particularly of smiling, would enable a deeper understanding of the relationship
      between physical changes and psychosocial adjustment in patients being treated
      for facial cancer. This study proposes 48 quantitative facial expression
      measures, which consist of the length normalized distances and slopes between 27
      manually annotated fiducial points on standard 2D clinical photographs of
      patients with head and neck cancer. Using the proposed measures, the maximum
      intensity of smiling for patients with head and neck cancer prior to their
      treatments was compared to that of a sample from a healthy population. A total of
      7 facial expression measures captured statistically significant differences
      between patients with head and neck cancer and healthy individuals. These
      measures suggest that patients with head and neck cancer are less expressive than
      people without head and neck cancer. This study is the first attempt to quantify
      the facial expression of patients with head and neck cancer and to build a
      foundation for studying how surgical interventions may affect their facial
      expressions. Moreover, this study lays the groundwork for future investigation of
      the relationship between facial expression and psychosocial adjustment in cancer
      patients. 

PMID- 24110536
TI  - Vascular pattern localization via temporal signature.
AB  - Accurate vascular pattern localization has many applications in the diverse
      scientific and application domains. For example, vascular patterns not only have
      been widely used as a biometric-based human identification method that is
      inexpensive, secure and easy to use, but also have produced more accurate heart
      rate estimation using conventional RGB camera by defining regions of interest
      along the vascular patterns instead of the entire exposed skin area. In addition,
      extracting temporal activity along vascular patterns can further enable targeted
      monitoring of other physiological parameters, such as blood flow and blood pulse
      transition time. This paper presents a method for robust and accurate vascular
      pattern localization using conventional RGB imaging systems. Our approach
      overcomes current limitations of systems that use still RGB images for vascular
      pathway localization - which produce low contrast between areas of vascular
      patterns and skin tissues and are sensitive to skin color variations - by
      capturing the temporal differences between these two areas from RGB videos. 

PMID- 24110537
TI  - Integral scale histogram local binary patterns for classification of narrow-band
      gastroenterology images.
AB  - The introduction of various novel imaging technologies such as narrow-band
      imaging have posed novel image processing challenges to the design of computer
      assisted decision systems. In this paper, we propose an image descriptor referred
      to as integrated scale histogram local binary patterns. We propagate an
      aggregated histogram of local binary patterns of an image at various resolutions.
      This results in low dimensional feature vectors for the images while
      incorporating their multiresolution analysis. The descriptor was used to classify
      gastroenterology images into four distinct groups. Results produced by the
      proposed descriptor exhibit around 92% accuracy for classification of
      gastroenteroloy images outperforming other state-of-the-art methods, endorsing
      the effectiveness of the proposed descriptor.

PMID- 24110538
TI  - Effect of phase difference in multi-antenna microwave thermal ablation for breast
      cancer treatment.
AB  - It was realized that cancer in breast is one of the most health hazards
      threatening women around the world for many years. Thermal ablation by using
      microwave energy is another alternative surgical maneuver due to its minimally
      invasive therapeutic technique. In this research, we investigate an effect of
      phase difference between three adjacent opened-slot coaxial probes in a multiple
      antenna alignment of microwave thermal ablation system for breast cancer
      treatment. FEM by using COMSOL is an implementation tools to simulate for 0, 45,
      90, 135 and 180 degree of phase difference. 3D Simulation results show that
      temperature distribution pattern, destructive volume and SAR in breast tissue are
      affected from those phase-shift utilization in multi-antenna system
      significantly.

PMID- 24110539
TI  - Temperature distributions measurement of high intensity focused ultrasound using
      a thin-film thermocouple array and estimation of thermal error caused by viscous
      heating.
AB  - To improve the throughput of high intensity focused ultrasound (HIFU) treatment,
      we have considered a focus switching method at two points. For this method, it is
      necessary to evaluate the thermal distribution under exposure to ultrasound. The
      thermal distribution was measured using a prototype thin-film thermocouple array,
      which has the advantage of minimizing the influence of the thermocouple on the
      acoustic and temperature fields. Focus switching was employed to enlarge the area
      of temperature increase and evaluate the proposed evaluation parameters with
      respect to safety and uniformity. The results indicate that focus switching can
      effectively expand the thermal lesion while maintaining a steep thermal boundary.
      In addition, the influence caused by the thin-film thermocouple array was
      estimated experimentally. This thermocouple was demonstrated to be an effective
      tool for the measurement of temperature distributions induced by HIFU. 

PMID- 24110540
TI  - MRI-compatible ultrasound heating system with ring-shaped phased arrays for
      breast tumor thermal therapy.
AB  - Therapeutic ultrasound transducers can carry out precise and efficient power
      deposition for tumor thermal therapy under the guidance of magnetic resonance
      imaging. For a better heating, organ-specific ultrasound transducers with
      precision location control system should be developed for tumors located at
      various organs. It is feasible to perform a better heating for breast tumor
      thermal therapy with a ring-shaped ultrasound phased-array transducer. In this
      study, we developed ring-shaped phased-array ultrasound transducers with 1.0 and
      2.5 MHz and a precision location control system to drive the transducers to the
      desired location to sonicate the designated region. Both thermo-sensitive
      hydrogel phantom and ex vivo fresh pork were used to evaluate the heating
      performance of the transducers. The results showed that the ring-shaped phased
      array ultrasound transducers were very promising for breast tumor heating with
      the variation of heating patterns and without overheating the ribs. 

PMID- 24110541
TI  - Temperature feedback based heating strategy for ultrasound thermal surgery.
AB  - Phased array transducer has the ability to generate multiple-focus pattern by
      adjusting the driving signal of individual element of the array. For the
      treatment of large target volume, several multiple-focus pattern could be used by
      using temporal switching technique among these power patterns. Typically, to
      obtain a uniform thermal dose, properly adjust the power level within the target
      volume is important. In this study, we proposed a temperature feedback based
      heating strategy without the need of power level adjustment. Several parameters,
      such as the setting temperature, sonication time, power level and blood
      perfusion, may affect the final thermal dose. Simulation results show that
      setting temperature is the key parameter to determine the final thermal dose
      while the effects of blood perfusion could be neglected and the sonication time
      should be as short as possible. Small power level is not suggested because the
      resulting thermal dose would extended owing to the thermal conduction. 

PMID- 24110542
TI  - Design of fiber optic applicators for laser interstitial thermotherapy:
      theoretical evaluation of thermal outcomes.
AB  - Thermal effects of different applicators for energy deposition in tissue
      undergoing laser interstitial thermotherapy (LITT) are investigated. The aim is
      to predict temperature distribution (T), dimensions and shape of thermal lesion
      produced by the laser light absorption within the tissue, in order to achieve an
      optimal design of the applicator for LITT. A numerical model, based on Monte
      Carlo method, was implemented to predict the distribution of laser light within
      the tissue, and the Bio Heat Equation was used to simulate T. Four geometries of
      optical applicators with different emitting surfaces were considered: bare fiber,
      cylindrical, zebra and a hybrid geometry. Effects on liver tissue undergoing LITT
      were evaluated in terms of T and coagulation volumes. Simulations were performed
      with laser power of 3 W and 5 W and energy of 1650 J. Results show that bare
      fiber causes an irregular coagulation shape; zebra and hybrid applicators 3 cm
      long obtain an elliptical lesion, with lowest maximum T (Tmax) on their surface
      (about 350 K); cylindrical applicators with length of 1 cm or 1.5 cm produce
      spherical lesions, with Tmax up to 398 K. Results suggest that the selection of
      the applicator based on the geometry of the lesion could improve LITT outcome.
      Furthermore, an appropriate geometry can preserve applicator integrity avoiding
      excessive temperature increase on its surface. 

PMID- 24110543
TI  - Influence of FBG sensors length on temperature measures in laser-irradiated
      pancreas: theoretical and experimental evaluation.
AB  - Temperature distribution T(x,y,z,t) in tissue undergoing Laser-induced
      Interstitial Thermotherapy (LITT) plays a crucial role on treatment outcome.
      Theoretical and experimental assessment of temperature on ex vivo laser
      irradiated pancreas is presented. The aim of this work is to assess the influence
      of thermometers dimensions on temperature measures during LITT. T(x,y,z,t) inside
      tissue is monitored by optical sensors, i.e., Fiber Bragg Gratings (FBGs): three
      FBGs with lengths of 10 mm and nine FBGs of 1 mm, at different distances (2 mm, 5
      mm and 10 mm) and different quotes (0 mm, 2 mm and 4 mm) from the laser fiber tip
      are used. Theoretical punctual T(x,y,z,t) is averaged out on both 10 mm and 1 mm
      in order to compare numerical predictions with experimental data. Results
      demonstrate the influence of FBG length on T(x,y,z,t) measures. This phenomenon
      depends on the distance between sensor and applicator: it is particularly
      significant close to the applicator tip (2 mm) because of the high spatial
      T(x,y,z,t) gradient within the tissue. Both theoretical results and experimental
      ones show that just at a distance of 10 mm from the tip, differences between
      T(x,y,z,t) provided by FBGs of 10 mm and 1 mm are negligible. 

PMID- 24110544
TI  - Automatic control system of brain temperature by air-surface cooling for
      therapeutic hypothermia.
AB  - An automatic control system of brain temperature by air-surface cooling was
      developed for therapeutic hypothermia, which is increasingly recommended for
      hypoxic-ischemic encephalopathy after cardiac arrest and neonatal asphyxia in
      several guidelines pertinent to resuscitation. Currently, water-surface cooling
      is the most widespread cooling method in therapeutic hypothermia. However, it
      requires large electric power for precise control and also needs water-cooling
      blankets which have potential for compression of patients by its own weight and
      for water leakage in ICU. Air-surface cooling does not have such problems and is
      more suitable for clinical use than water-surface cooling, because air has lower
      specific heat and density as well as the impossibility of the contamination in
      ICU by its leakage. In the present system, brain temperature of patients is
      automatically controlled by suitable adjustment of the temperature of the air
      blowing into the cooling blankets. This adjustment is carried out by the
      regulation of mixing cool and warm air using proportional control valves. The
      computer in the developed control apparatus suitably calculates the air
      temperature and rotation angle of the valves every sampling time on the basis of
      the optimal-adaptive control algorithm. Thus, the proposed system actualizes
      automatic control of brain temperature by the inputting only the clinically
      desired temperature of brain. The control performance of the suggested system was
      verified by the examination using the mannequin in substitution for an adult
      patient. In the result, the control error of the head temperature of the
      mannequin was 0.12  degrees C on average in spite of the lack of the production
      capacity of warm air after the re-warming period. Thus, this system serves as a
      model for the clinically applied system.

PMID- 24110545
TI  - Optimizing bipolar radiofrequency ablation treatment by means of pulsed currents.
AB  - Given the high mortality rate, liver cancer is considered to be a difficult
      cancer to treat. Consequently, alternative strategies are being developed such as
      radiofrequency ablation (RFA). RFA applies radiofrequent currents leading to
      local heating of the tumoral tissue. Accurate numerical modeling contributes to a
      better knowledge of the physical phenomena and allows optimizations. In this
      work, the bipolar radiofrequency ablation technique is explored followed by an
      optimization by means of pulsed currents. Numerical results clearly show the
      larger ablation zones due to the pulsed currents. Hence, pulsed bipolar RFA
      increases the efficacy and has the potential to be incorporated in clinical
      practice. 

PMID- 24110546
TI  - Superficial heat reduction technique for a hybrid microwave-optical device.
AB  - Microwave applicator in the form of a circularly polarized microstrip patch
      antenna is proposed to provide localized deep heating in biological tissue, which
      causes blood vessels to dilate leading to changes in tissue oxygenation. These
      changes are monitored by an integrated optical system for studying
      thermoregulation in different parts of the human body. Using computer
      simulations, this paper compares circularly and linearly polarized antennas in
      terms of the efficiency of depositing electromagnetic (EM) energy and the heating
      patterns. The biological model composes of the skin, fat and muscle layers with
      appropriate dielectric and thermal properties. The results show that for the same
      specific absorption rate (SAR) in the muscle, the circularly polarized antenna
      results in a lower SAR in the skin-fat interface than the linearly polarized
      antenna. The thermal distribution is also presented based on the biological heat
      equation. The proposed circularly polarized antenna shows heat reduction in the
      superficial layers in comparison to the linearly polarized antenna. 

PMID- 24110547
TI  - Computation of temperature elevation in fetus due to radio-frequency exposure
      with a new thermal modeling.
AB  - The temperature elevation in the fetus is of concern for radio-frequency
      exposure. According to the IEC standard, the temperature elevation in the fetus
      should be lower than 0.5  degrees C for exposure in magnetic resonance equipment.
      However, no previous study succeeded to simulate the temperature difference
      between the fetus and mother in the thermoneutral condition. The present study
      proposes a new thermal modeling for the pregnant woman model. The thermal
      modeling is then applied to the temperature variation for plane wave exposure at
      80 MHz. From computational results, the core temperature in the fetus at the
      thermoneutral condition was 37.5  degrees C, which is 0.35  degrees C larger than
      that of the mother and coincident with measured data. When the pregnant woman
      model is irradiated by the plane wave with the whole-body averaged specific
      absorption rate of 2 W/kg for 1 hour, the temperature elevation in the fetus is
      0.50  degrees C, which is larger than that in the mother by 0.11  degrees C.

PMID- 24110548
TI  - Control of rapid hypothermia induction by total liquid ventilation: preliminary
      results.
AB  - Mild therapeutic hypothermia (MTH) consists in cooling the body temperature of a
      patient to between 32 and 34  degrees C. This technique helps to preserve tissues
      and neurological functions in multi-organ failure by preventing ischemic injury.
      Total liquid ventilation (TLV) ensures gas exchange in the lungs with a liquid,
      typically perfluorocarbon (PFC). A liquid ventilator is responsible for ensuring
      cyclic renewal of tidal volume of oxygenated and temperature-controlled PFC.
      Hence, TLV using the lung as a heat exchanger and PFC as a heat carrier allows
      ultra fast cooling of the whole body which can help improve outcome after
      ischemic injuries. The present study was aimed to evaluate the control
      performance and safety of automated ultrarapid MTH induction by TLV.
      Experimentation was conducted using the Inolivent-5.0 liquid ventilator equipped
      with a PFC treatment unit that allows PFC cooling and heating from the flow of
      energy carrier water inside a double wall installed on an oxygenator. A water
      circulating bath is used to manage water temperature. A feedback controller was
      developed to modulate inspired PFC temperature and control body temperature. Such
      a controller is important since, with MTH induction, heart temperature should not
      reach 28  degrees C because of a high risk of fibrillation. The in vivo
      experimental protocol was conducted on a male newborn lamb of 4.7 kg which, after
      anesthetization, was submitted to conventional gas ventilation and instrumented
      with temperature sensors at the femoral artery, oesophagus, right ear drum and
      rectum. After stabilization, TLV was initiated with fast automated MTH induction
      to 33.5  degrees C until stabilization of all temperatures. MTH could be reached
      safely in 3 minutes at the femoral artery, in 3.6 minutes at the esophagus, in
      7.7 minutes at the eardrum and in 15 minutes at the rectum. All temperatures were
      stable at 33.5 +/- 0.5  degrees C within 15 minutes. The present results reveal
      that ultra-fast MTH induction by TLV with Inolivent-5.0 is safe for the heart
      while maintaining esophageal and arterial temperature over 32.6  degrees C. 

PMID- 24110549
TI  - Mid-long term effect of non-ablative high radiofrequency therapy on the rabbit
      dermal extracellular matrix.
AB  - This study quantitatively investigated the postoperative effects of
      radiofrequency (RF) application on the normal dermal extracellular matrix (ECM)
      of in vivo rabbits. Postoperative effects were evaluated by histology and atomic
      force microscopy analysis of dermal tissues treated using three RF energy levels
      (10 ~ 30 W) and either a single- or multiple-pass procedure. Progressive changes
      in the morphology of rabbit dermal ECMs were investigated over a 30-day
      postoperartive period. All RF-treated groups, except for the low energy group (10
      W), displayed more prominent inflammatory responses compared to the control. This
      inflammatory reaction was more prominent a day after application. Dermal tissues
      30 days after RF application exhibited prominent myofibroblast activity
      associated with ECM contractile activity during wound healing in addition to
      chronic inflammation. A decrease in the morphology of dermal ECMs after RF
      application continued until seven days postoperatively. The ECM diameter
      increased to near baseline at 30 days postoperatively. Low energy and multi-pass
      applications resulted in greater collagen fibril contraction and recovery at the
      ultra-structural level at 30 days postoperatively than did a single high energy
      application.

PMID- 24110550
TI  - A practical comparison of Copper Bromide Laser for the treatment of vascular
      lesions.
AB  - The recent rapid growth in demand for aesthetic non-invasive laser treatments
      such as unwanted skin rejuvenation, removal of age-related vascular blemishes has
      led to a boom in the medical devices to treat these conditions. Among diverse
      laser for skin treatment, copper bromide laser is a very effective, safe, and
      well tolerated treatment for facial telangiectasia at various energy levels and
      the most important thing of the copper bromide laser device is that the stability
      of the energy. However there is no evidence about effective copper bromide
      laser's energy level for the treatment of vascular lesions. We compared energy
      stability and treatment performance between two energy levels in 2 W and 8 W
      which commonly use in laser treatment for the vascular lesions. 8 W copper
      bromide laser was more stable compared than 2 W copper bromide laser. Also, 8 W
      copper bromide laser was effectively superior to 2 W copper bromide laser in
      treatment of vascular legion. Consequently, 8 W copper bromide laser treatment
      for vascular lesion might be more suitable than 2 W copper bromide laser.

PMID- 24110551
TI  - New treatment strategy of cryosurgery and temperature control.
AB  - Cryosurgery, recommended as an effective method for tumor treatment, has been
      widely used in clinics. However, it might lead to a high probability of tumor
      recurrence due to incomplete tumor damage. The treatment protocol for cryosurgery
      is essential to achieve the desired therapeutic effects. In this study, a new
      temperature fluctuation treatment method was proposed, and the fuzzy control
      method based on piecewise adjustment was developed for temperature control during
      the treatment. Ex vivo rat liver experiments were conducted and histopathology
      analysis used to study the therapeutic effects of the new treatment method. 

PMID- 24110552
TI  - Detection of transient, regional cardiac repolarization alternans by time
      frequency analysis of synthetic electrograms.
AB  - Repolarization alternans (RA), originating at the cellular level, is thought to
      produce an arrhythmogenic substrate, and surface ECG T-wave alternans (TWA) is a
      marker of risk for sudden cardiac death. In this paper we study RA in the
      unipolar electrograms (EGM), which represent the electrical activity of the heart
      at the tissue level. We first describe a simple analytical model to study how RA,
      simulated as alternating variations of action potential duration, affects EGM
      TWA, and then we propose a novel methodology based on time-frequency analysis to
      detect EGM-TWA which occurs intermittently in few consecutive beats. In a
      simulation study, we used a 257-node whole heart model to reproduce several
      patterns of RA. RA involved specific subsets of adjacent nodes (11, 65 and 257),
      exhibited different amplitudes (0.25, 0.5 and 1 ms) and lasted for 40 consecutive
      beats of a 80-beat-long test sequence. Results show a relationship between the
      spatial distribution of RA and EGM-TWA: the smaller the region where RA occurs,
      the higher the extent of EGM-TWA. With the proposed methodology, we localized
      those portions of myocardium which exhibited EGM-TWA with an accuracy higher than
      90%. 

PMID- 24110553
TI  - Mapping activation in a sinoatrial node cardiac tissue preparation with a multi
      electrode array.
AB  - An isolated rabbit cardiac sinoatrial node (SAN) tissue preparation was used
      experimentally to map activation times and conduction velocities of extracellular
      cardiac action potential (AP) propagation. Extracellular recordings were carried
      out using a two-dimensional array of unipolar Ag-AgCl microelectrodes connected
      to a 128-channel data acquisition system. A 20(th) order, low-pass Butterworth
      filter, with a cut-off frequency of 50 Hz, was used in conjunction with a Matlab
      algorithm to map activation times and conduction velocities. Results show an
      initial slow-down of the activation wavefront emanating from the SAN, followed by
      acceleration in some regions, particularly near the Superior Vena Cava, as it
      travels towards the SAN periphery. 

PMID- 24110554
TI  - Wavelet-sparsity based regularization over time in the inverse problem of
      electrocardiography.
AB  - Noninvasive, detailed assessment of electrical cardiac activity at the level of
      the heart surface has the potential to revolutionize diagnostics and therapy of
      cardiac pathologies. Due to the requirement of noninvasiveness, body-surface
      potentials are measured and have to be projected back to the heart surface,
      yielding an ill-posed inverse problem. Ill-posedness ensures that there are non
      unique solutions to this problem, resulting in a problem of choice. In the
      current paper, it is proposed to restrict this choice by requiring that the time
      series of reconstructed heart-surface potentials is sparse in the wavelet domain.
      A local search technique is introduced that pursues a sparse solution, using an
      orthogonal wavelet transform. Epicardial potentials reconstructed from this
      method are compared to those from existing methods, and validated with actual
      intracardiac recordings. The new technique improves the reconstructions in terms
      of smoothness and recovers physiologically meaningful details. Additionally,
      reconstruction of activation timing seems to be improved when pursuing sparsity
      of the reconstructed signals in the wavelet domain. 

PMID- 24110555
TI  - A working heart-brainstem preparation of the rat for the study of reflex mediated
      autonomic influences on atrial arrhythmia development.
AB  - Vagal nerve activity has been shown to play a role in the formation and
      maintenance of atrial fibrillation (AF). Nerves on the atria are now increasingly
      being targeted using ablation-based therapies for the treatment of paroxysmal AF.
      In vivo, changes in vagal activity are part of an integrated autonomic profile
      that invariably involves accompanying modulations in sympathetic activity. To
      date, it has not been possible to replicate endogenous profiles of autonomic
      activity with the experimental set-ups used to study the effects of vagal
      stimulation on AF development. In this paper, we describe an experimental set-up
      using an in situ preparation that addresses these challenges for the first time.
      A high resolution surface electrode array has been used to make recordings of
      atrial electrograms during baroreflex activation from a preparation with intact
      innervation from brainstem to heart. This provides a novel framework for relating
      reflex-mediated autonomic activity to altered regional impulse propagation and
      electrical rhythm in the atria. 

PMID- 24110556
TI  - Methodology for automated detection of fragmentation in QRS complex of Standard
      12-lead ECG.
AB  - Fragmented QRS (f-QRS) has been found to have higher sensitivity and/or
      specificity values for several diseases including remote and acute myocardial
      infarction, cardiac sarcoidosis etc, compared to other conventional bio-markers
      viz. Q-wave, ST-elevation etc. Several of these diseases do not have a reliable
      bio-marker and hence, patients suffering from them have to undergo expensive and
      sometimes invasive tests for diagnosis viz. myocardial biopsy, cardiac
      catheterization etc. This paper proposes automation of fragmentation detection
      which will lead to a more reliable diagnosis and therapy reducing human error,
      time consumption and thereby alleviating the need of enormous training required
      for detection of fragmentation. In this paper, we propose a novel approach to
      detect the discontinuities present in QRS complex of standard 12-lead ECG, known
      as fragmented QRS, using Discrete Wavelet transform (DWT) targeting both hospital
      based and remote health monitoring environments. Fragmentation Detection
      Algorithm (FDA) was designed and modeled using PhysioNet's PTBDB and upon
      reiterative refinements it successfully detected all discontinuities in the QRS
      complex. The QRS complexes of 31 patients obtained randomly from PhysioNet's
      PTBDB were examined by two experienced cardiologists and the measurements
      obtained were compared with the results of our proposed FDA leading to 89.8%
      agreement among them. 

PMID- 24110557
TI  - Two dimensional wavelet energy analysis on a beat to beat basis: application to
      Atrial Fibrillation.
AB  - Atrial Fibrillation (AF) is a condition in which heart rhythm is not associated
      with normal sinoatrial (SA) node pacemaker but it derives from different areas on
      the atrium, often from the area of Pulmonary veins (PVs) A way to eliminate the
      influence of PVs in the inducement of AF is the PVs isolation surgery. In this
      study, an effort is made towards investigating the morphology and dynamics of P
      waves, when the potentially arrhythmogenic tissue in PVs is involved or isolated
      via ablation. For this reason, 20 patients who were subjected to PVs isolation
      were studied, via vectrorcardiography recordings obtained before and after the
      ablation. Wavelet energies for five frequency bands were analyzed, using a two
      dimensional representation. The proposed technique was applied for the analysis
      of wavelet energies in consecutive beats, and their correlation with the RR
      interval. Features for the evaluation of those plots were extracted, such as the
      axes of a fitted to the plot ellipse and the center of the mass. The statistical
      analysis demonstrated significant differences between the groups, which imply the
      modification of the atrial substrate concerning electrical conduction toward to a
      more stable condition. 

PMID- 24110558
TI  - Computing the electrical activity of the heart with a dynamic inverse monodomain
      operator.
AB  - The inverse problem in electrocardiography is to reconstruct the voltage in the
      surface of the heart, using a high density electrocardiogram. This problem is
      usually solved using regularization techniques, which tend to give the minimum
      energy response in a static scheme. In our work, we propose to calculate a
      dynamic inverse solution using the Monodomain as a model of electrical heart
      activity, thus constraining the family of solutions to one that satisfies the
      model. 

PMID- 24110559
TI  - Cardiovascular changes in parabolic flights assessed by ballistocardiography.
AB  - This paper presents a comparison of the cardiovascular changes observed in
      microgravity as compared to ground based measurements. The ballistocardiogram
      (BCG), the electrocardiogram (ECG) and the transthoracic impedance cardiogram
      (ICG) were recorded on five healthy subjects during the 57th-European Space
      Agency (ESA) parabolic flight campaign. BCG is analyzed though its most
      characteristic wave, the IJ wave complex that can be identified along the
      longitudinal component of BCG and which has been demonstrated to be linked to
      cardiac ejection. The timings between the contraction of the heart and the
      ejection of blood in the aorta are analyzed via the time delay between the R-wave
      of the ECG and the I and J-waves of BCG (RI and RJ intervals respectively). Our
      results show that the IJ complex presents a larger amplitude in weightlessness
      and suggest that stroke volume (SV) increases in microgravity. We assume that
      ballistocardiography is an efficient method to assess the ventricular
      performance. 

PMID- 24110560
TI  - Effects of L-type Ca2+ channel blocker nifedipine on dynamic arterial blood
      pressure control.
AB  - Dynamic characteristics of arterial pressure (AP) regulation are important
      components in our understanding of rapid AP restoration by the arterial
      baroreflex system. The present study examined the effects of an L-type Ca(2+)
      channel blocker nifedipine on baroreflex-mediated dynamic AP regulation. In
      anesthetized and vagotomized rats, carotid sinus pressure was externally
      perturbed using a Gaussian white noise signal, and the neural arc transfer
      function from pressure input to efferent sympathetic nerve activity (SNA) and the
      peripheral arc transfer function from SNA to AP were identified. The peripheral
      arc transfer function approximated a second-order low-pass filter with pure dead
      time. Intravenous administration of nifedipine significantly decreased the steady
      state gain and increased the damping ratio of the peripheral arc without
      affecting the dynamic characteristics of the neural arc. When the step response
      of AP was calculated based on the peripheral arc transfer function alone,
      nifedipine prolonged 80% rise time by 26%. When the closed-loop AP response was
      simulated based on both the neural arc and peripheral arc transfer functions and
      the dynamic gain of the baroreflex total loop was assumed to be 2.0, nifedipine
      prolonged 80% recovery time by 107%. In conclusion, L-type Ca(2+) channel
      blockade may compromise the baroreflex-mediated AP control not only in the
      magnitude but also in the speed of AP restoration. 

PMID- 24110561
TI  - Differential dynamic control of cardiac and splanchnic sympathetic nerve activity
      by the arterial baroreflex.
AB  - The arterial baroreflex is the primary negative feedback system involved in
      stabilizing arterial pressure from external disturbances. Determining the dynamic
      characteristics of the baroreflex is important for our understanding of the
      mechanisms involved in rapid restoration of arterial pressure. This study
      examined the differences in the dynamic baroreflex control of cardiac (CSNA) and
      splanchnic (SSNA) sympathetic nerve activity. The baroreceptor region of the
      right aortic depressor nerve was isolated from the systemic circulation to
      control baroreceptor region pressure (BRP) with a Gaussian white noise signal
      while simultaneously recording CSNA and SSNA in anesthetized Sprague-Dawley rats.
      SSNA was recorded from a postganglionic branch of the splanchnic sympathetic
      nerve and CSNA was recorded from a branch of the left stellate ganglion. Neural
      arc transfer functions from BRP to SSNA (HSSNA) and BRP to CSNA (HCSNA) displayed
      derivative characteristics. When dynamic gain below 0.03 Hz was normalized to
      unity, HSSNA had a higher gain at frequencies 0.1 and 1 Hz and increasing slope
      from 0.1 to 1 Hz relative to HCSNA. The peak decrease in the step response was
      higher for SSNA than CSNA. These data indicate differential dynamic baroreflex
      control of SSNA and CSNA. Rapid changes in baroreceptor pressure input would
      result in a larger response in SSNA compared with CSNA. 

PMID- 24110562
TI  - A novel approach to the design of an artificial bionic baroreflex.
AB  - This paper presents a computationally efficient method to design an artificial
      bionic baroreflex. This work is built upon a physiology-based mathematical model
      of autonomic-cardiac regulation describing the regulation of heart rate and blood
      pressure as well as a system identification technique to identify a subject
      specific mathematical model for each subject. The control strategy to regulate
      blood pressure is developed based upon the in-vivo baroreflex mechanism. A unique
      strength of the proposed method is its capability to determine the modulating
      baroreflex functions on the sympathetic and parasympathetic nerve activities.
      This method can be used in the treatment of individuals with baroreflex failure
      through overriding the corresponding nerves to properly regulate blood pressure.
      In fact, nerve overriding causes heart rate and arterial stiffness to adjust such
      that blood pressure reaches a proper range to provide enough oxygenated-blood to
      the critical organs. 

PMID- 24110563
TI  - Microfabricated device for co-culture of sympathetic neuron and iPS-derived
      cardiomyocytes.
AB  - Induced pluripotent stem (iPS) cell-derived cardiomyocytes (iPS-CMs) has been
      expected as a cell source for therapy of serious heart failure. However, it is
      unclear whether the function of iPS-CMs is modulated by the host sympathetic
      nervous system. Here we developed a device for co-culture of sympathetic neurons
      and iPS-CMs using microfabrication technique. The device consisted of a culture
      chamber and a microelectrode-array (MEA) substrate. The superior cervical
      ganglion (SCG) neurons were co-cultured with iPS-CMs in a microfabricated device,
      which had multiple compartments. Several days after seeding, synapses were formed
      between SCG neurons and iPS-CMs, as confirmed by immunostaining. Spontaneous
      electrical activities of the SCG neurons and the iPS-CMs were observed from the
      electrode of the MEA substrate. The beat rate of iPS-CMs increased after
      electrical stimulation of the co-cultured SCG neurons. Such changes in the beat
      rate were prevented in the presence of propranolol, a beta-adrenoreceptor
      antagonist. These results suggest that the microfabricated device will be
      utilized for studying the functional modulation of iPS-CMs by connected
      sympathetic neurons. 

PMID- 24110564
TI  - Investigating the beat by beat phase synchronization between maternal and fetal
      heart rates.
AB  - The development of the fetal cardiovascular system plays a crucial role in fetal
      health. The evolution of the relationship between fetal and maternal cardiac
      systems during fetal maturation is a characterizing feature for fetal cardiac
      development. This paper aims to evaluate this relationship by investigating the
      beat-to-beat synchronization between fetal and maternal heart rates and its
      variation at different stages of pregnancy. Synchronization epochs and phase
      locking patterns are analyzed at certain synchronization ratios (SRs) for three
      gestational age groups (16-26 weeks, 27-33 weeks, 34-40 weeks). Results show that
      the normalized synchronization epoch is significantly different for three age
      groups with the p-value of 6.72*10(-6) and 2.89*10(-4) at SR of 1:2 and 4:5
      respectively. The variance of phase locking also shows significant difference for
      three groups with the p-value less than 10(-7) at four SRs. Results also suggest
      that synchronization may be the force behind the increase in the maternal heart
      rate to maintain the fetal development and provide supplies for the fetus.
      Overall, the findings propose new clinical markers for evaluating the antenatal
      development.

PMID- 24110565
TI  - An extended model of blood pressure variability: incorporating the respiratory
      modulation of vascular resistance.
AB  - Short-term blood pressure variability is generally attributed to the baroreflex
      feedback control on heart rate and systemic vascular resistance (SVR), and the
      mechanical effect of respiration on stroke volume. Although it is known that
      respiration affects sympathetic outflow and deep breaths can lead to peripheral
      vasoconstriction, the respiratory modulation of SVR has been little studied. In
      the present study, we investigated the dynamics resulting from the respiratory
      modulation of SVR and its effect on blood pressure variability by employing
      structured and minimal modeling approaches. Using peripheral arterial tonometry
      as a noninvasive measure of SVR, we were able to estimate the respiratory
      vascular conductance coupling mechanism. We found that the dynamics of the sigh
      vasoconstriction reflex could be reproduced only when the respiratory modulation
      of SVR was incorporated into the closed-loop model. Lastly, we demonstrated that
      taking this respiratory modulation effect into account is essential for
      accurately estimating the dynamics of the SVR baroreflex. 

PMID- 24110566
TI  - Estimation of respiratory signal from thoracic impedance cardiography in low
      electrical current.
AB  - A new method to estimate respiratory signal from thoracic impedance is proposed.
      To realize battery powered, wearable respiratory monitoring devices, low current
      impedance measurement techniques are desired. However, under low current
      conditions, conventional methods to separate cardiac and respiratory signals do
      not work well as the cardiac signal is much larger than the respiratory signal.
      In the proposed method, respiratory signal is estimated by calculating an
      envelope curve from the detected T waves of cardiac component. The results of the
      experiments show that the accuracy of proposed method is greater than
      conventional method. 

PMID- 24110567
TI  - Further applications of Doppler radar for non-contact respiratory assessment.
AB  - This paper further investigates the use of Doppler radar for detecting and
      identifying certain human respiratory characteristics from observed frequency and
      phase modulations. Specifically, we show how breathing frequencies can be
      determined from the demodulated signal leading to identifying abnormalities of
      breathing patterns using signal derivatives, optimal filtering and standard
      statistical measures. Specifically, we report results on a robust method for
      distinguishing cessation of the normal breathing cycle. The proposed approach can
      have potential application in the management of sudden infant death
      syndrome(SIDS) and sleep apnea. 

PMID- 24110568
TI  - Development of a new measurement system to detect selectively volatile organic
      compounds derived from the human body.
AB  - A new concept expired gas measurement system used double cold-trap method was
      developed. The system could detect selectively volatile organic compound (VOC)
      derived from the human body. The gas chromatography (GC) profiles of healthy
      volunteer's expired gas collected by our system were analyzed. As a result, 60
      VOCs were detected from the healthy volunteer's expired gas. We examined 14 VOCs
      among them further, which could be converted to the concentration from the GC
      profiles. The concentration of almost VOCs decreased when the subjects inspired
      purified air compared with the atmosphere. On the other hand, isoprene was almost
      the same. It was strongly suggested that these VOCs were derived from the human
      body because the concentration of these VOCs in the atmosphere were nearly zero.
      Expired gas of two sleep apnea syndrome (SAS) patients were analyzed as
      preliminary study. As a result of the study, the concentration of some VOCs
      contained in the expired gas of the SAS patients showed higher value than a
      healthy controls. 

PMID- 24110569
TI  - Fundamental study of measurement of cardiorespiratory signals in a sitting
      position using piezoelectric sensors.
AB  - In this paper, we propose a measurement system to extract the heartbeat and
      respiration signals from piezoelectric sensors located in a chair seat. Eight
      healthy male subjects (22-26 years old) sat on a chair with piezoelectric
      sensors. The experiment consisted of five acquisitions (300 s recording with 30 s
      resting). In the 1st acquisition, the subject was instructed to maintain a relax
      state. During the next three acquisitions, the subject maintained respiration
      rates of 3, 4, and 5 s. The order was randomly given for each subject. Finally,
      the subject was instructed to stay in a resting state for 300 s. Band-pass
      filters were used to separate the heartbeat and respiration signals from the
      output signal of the piezoelectric sensors (heartbeat: 0.7-7 Hz, respiration: 0.1
      0.4 Hz). Then, the standard heartbeat interval was calculated using the
      autocorrelation function to generate a template. Heartbeat and respiration
      signals were extracted using a two-dimensional cross-correlation pattern matching
      method. For validation, the error ratio between the piezoelectric sensor data and
      the reference data was determined. The error ratios of the heartbeat interval and
      respiration interval were 2.89 +/- 4.41% and 5.57 +/- 4.42%, respectively.
      Therefore, it is suggested that heartbeat and respiration signals extracted from
      piezoelectric sensors in a sitting position can be used as an alternative method
      for extracting biological signals.

PMID- 24110570
TI  - Cardiac interference reduction in diaphragmatic MMG signals during a Maintained
      Inspiratory Pressure Test.
AB  - A recursive least square (RLS) adaptive filtering algorithm for reduction of
      cardiac interference in diaphragmatic mecanomyographic (MMGdi) signals is
      addressed in this paper. MMGdi signals were acquired with a capacitive
      accelerometer placed between 7th and 8th intercostal spaces, on the right
      anterior axillary line, during a maintained inspiratory pressure test. Subjects
      were asked to maintain a constant inspiratory pressure with a mouthpiece
      connected to a closed tube (without breathing). This maneuver was repeated at
      five different contraction efforts: apnea (no effort), 20 cmH2O, 40 cmH2O, 60
      cmH2O and maximum voluntary contraction. An adaptive noise canceller (ANC) using
      the RLS algorithm was applied on the MMGdi signals. To evaluate the behavior of
      the ANC, the MMGdi signals were analyzed in two segments: with and without
      cardiac interference (WCI and NCI, respectively). In both segments it was
      analyzed the power spectral density (PSD), and the ARV and RMS amplitude
      parameters for each contraction effort. With the proposed ANC algorithm the
      amplitude parameters of the WCI segments were reduced to a level similar to the
      one of the NCI segments. The obtained results showed that ANC using the RLS
      algorithm allows to significantly reduce the cardiac interference in MMGdi
      signals. 

PMID- 24110571
TI  - Characterization of the respiratory pattern variability of patients with
      different pressure support levels.
AB  - One of the most challenging problems in intensive care is still the process of
      discontinuing mechanical ventilation, called weaning process. Both an unnecessary
      delay in the discontinuation process and a weaning trial that is undertaken too
      early are undesirable. In this study, we analyzed respiratory pattern variability
      using the respiratory volume signal of patients submitted to two different levels
      of pressure support ventilation (PSV), prior to withdrawal of the mechanical
      ventilation. In order to characterize the respiratory pattern, we analyzed the
      following time series: inspiratory time, expiratory time, breath duration, tidal
      volume, fractional inspiratory time, mean inspiratory flow and rapid shallow
      breathing. Several autoregressive modeling techniques were considered:
      autoregressive models (AR), autoregressive moving average models (ARMA), and
      autoregressive models with exogenous input (ARX). The following classification
      methods were used: logistic regression (LR), linear discriminant analysis (LDA)
      and support vector machines (SVM). 20 patients on weaning trials from mechanical
      ventilation were analyzed. The patients, submitted to two different levels of
      PSV, were classified as low PSV and high PSV. The variability of the respiratory
      patterns of these patients were analyzed. The most relevant parameters were
      extracted using the classifiers methods. The best results were obtained with the
      interquartile range and the final prediction errors of AR, ARMA and ARX models.
      An accuracy of 95% (93% sensitivity and 90% specificity) was obtained when the
      interquartile range of the expiratory time and the breath duration time series
      were used a LDA model. All classifiers showed a good compromise between
      sensitivity and specificity. 

PMID- 24110572
TI  - Detection of respiration in central venous pressure using state machine.
AB  - Reliable information from patient monitors enhances treatment for critically ill
      patients. Redundant sources for information would aid identification of faulty
      sensors and leads, and improve presentation of physiological data. Respiratory
      information can be obtained from several sources, including airway pressure and
      central venous pressure (CVP). CVP signals have been analyzed using frequency
      information to isolate the respiration related part of the signal or to obtain
      statistics about respiration. This study uses a state machine algorithm to detect
      the timing of each cycle of respiration. A state machine has advantages of
      enforcing a predictable cycle of expiration and inspiration. The detection of
      respiratory cycles can be done in real-time, allowing identification of irregular
      periods between inspirations and prolonged periods with no inspiration, for which
      an alert may be issued. The algorithm was tested on data obtain from the
      PhysioNet database of recordings from intensive care patients. The airway
      pressure signal was used to determine the "true values" of the timing of each
      respiratory cycle for checking the accuracy of the algorithm analyzing the CVP
      signal. Parameters of the algorithm were found that would result in a true
      positive value of above 98% for detection of each cycle of respiration from
      analysis of the CVP signal, compared to analysis of the RESP signal. 

PMID- 24110573
TI  - Validation of a multi-scale model of the coronary circulation in adult sheep and
      newborn lambs.
AB  - We validated a multi-scale model of a left-dominant coronary circulation using
      high fidelity pressure and flow data acquired in adult sheep and newborn lambs.
      The model incorporated a one-dimensional representation of the major left conduit
      coronary arteries, allowing for the study of wave propagation effects. The
      coronary microvasculature was represented by regional instances of a lumped
      parameter model consisting of three transmural layers, each with two serial
      compartments accounting for compliance, resistance and intramyocardial pressure
      effects. Model inputs comprised measured aortic pressure/flow and ventricular
      pressure. Minimal data fitting was employed, with only measured mean coronary
      flow used to iteratively adjust total coronary resistance. The model was adapted
      to different heart sizes via allometric scaling. Excellent agreement was observed
      between model and experimental flow waveforms in the proximal circumflex artery,
      both in terms of the degree of systolic flow impediment and transient waveform
      features. The proposed multi-scale modelling approach is likely to be useful for
      studying phasic features of the coronary flow waveform, including coronary waves
      in different coronary anatomies and throughout development. 

PMID- 24110574
TI  - Role of endogenous hydrogen peroxide during angiotensin type 1 receptor blockers
      administration in pacing-induced metabolic coronary vasodilatation in dogs in
      vivo.
AB  - BACKGROUND: We have previously demonstrated that endothelium-derived hydrogen
      peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in canine
      coronary microcirculation in vivo. However, the role of H2O2/EDHF during
      angiotensin type 1 receptor blockers (ARB) administration in metabolic coronary
      dilatation in vivo remains to be examined. We examined whether H2O2 during ARB
      administration is involved in pacing-induced metabolic coronary vasodilatation in
      dogs in vivo and if so, whether such beneficial effects of ARB administration
      acutely improve coronary vasodilatation in diabetes mellitus (DM). METHODS:
      Canine subepicardial coronary small arteries (CSA,>= 100 MUm) and arterioles (CA,
      <100 MUm) in left anterior descending artery area were continuously observed by
      an intravital microscope under cyclooxygenase blockade(ibuprofen, 12.5 mg/kg,
      intravenous infusion, iv). Experiments were performed during paired right
      ventricular pacing under the following 4 conditions (n=5 each); (i) control, (ii)
      DM(alloxan 40 mg/ kg, iv, 1 week prior to study), (iii) DM+ARB(olmesartan, 10
      MUg/kg/min, 10 min, intracoronary infusion,ic)+L-NMMA (NOS inhibitor, 2 !mol/min,
      ic) and (iv)DM+ARB+catalase (H2O2 discomposer, 1000 U/ml, 5 min, ic). RESULTS:
      Cardiac tachypacing (60 to 120 bpm) caused coronary vasodilatation in both-sized
      arteries under control conditions. DM significantly decreased the vasodilatation
      compared with control in CSA and there was a residual vasodilatation for the loss
      of NO in CA, whereas DM+ARB+L-NMMA improved the vasodilatation compared with DM
      alone in CA and was significantly decreased by DM+ARB+catalase in CA.
      CONCLUSIONS: These results indicate that H2O2 during ARB administration is
      involved in pacing-induced metabolic coronary vasodilatation in DM in vivo and
      that there are substantial compensatory interactions between NO and H2O2.

PMID- 24110575
TI  - Area stenosis associated with non-invasive fractional flow reserve obtained from
      coronary CT images.
AB  - Fractional flow reserve (FFR) determined by invasive angiography is the gold
      standard to assess the severity of coronary artery disease (CAD). FFRCT can be
      obtained non-invasively by combining computed tomography (CT) images and
      Computational Fluid Dynamics (CFD) method. In this study, FFRCT was computed for
      6 models of patient-specific left coronary artery trees reconstructed from CT
      images. A total of 12 stenoses were observed. FFR values obtained for 7 of the 12
      stenoses during invasive angiography were used as the gold standard for
      comparison. On a per-stenosis basis, the sensitivity, specificity, positive
      predictive value and negative predictive value were 50%, 100%, 100% and 83.3%
      respectively for FFRCT. A weak correlation was found between percent lumen
      diameter stenosis and FFRCT (r=0.431; p>0.05). However, the correlation between
      percent lumen area stenosis and FFRCT was significant (r=0.853; p<0.05).
      Therefore, non-invasive FFRCT appears to be a promising index to assess the
      severity of CAD and lumen area has distinct advantages over diameter measurement
      in terms of anatomy assessment. 

PMID- 24110576
TI  - Effects of stenosis on the porcine left anterior descending arterial tree.
AB  - In this study, hemodynamics in the normal and diseased left anterior descending
      (LAD) arterial trees were compared to estimate the effects of stenosis on the
      flow rate distribution, detailed flow field and wall shear stress (WSS)
      distributions on both transient and steady flow conditions. The anatomical model
      was reconstructed from computed tomography (CT) images of a normal porcine heart.
      Stenosis was imposed at the trunk of LAD tree with different area stenosis ratios
      (25%, 50%, 75% and 90%) to study the effect of stenosis. It has been found that
      the steady-state simulation is competent to demonstrate the prominent flow
      features of transit flow. Only significant stenosis altered the flow rate
      considerably, and its effects diminished at the downstream bifurcations. Based on
      the WSS distribution, non-significant stenosis potentially led to the development
      of atherosclerosis near the ostium of the downstream side branch and significant
      stenosis might promote atherosclerosis in its wake. 

PMID- 24110577
TI  - Automatic measurement of lumen diameter of carotid artery in A-Mode ultrasound.
AB  - Accurate measurement of lumen diameter is essential for correct estimation of
      arterial compliance. We have been developing a new non-invasive arterial
      compliance measurement tool using a single element ultrasound transceiver. In
      this paper we propose a new method for measurement of lumen diameter from single
      line of Radio-Frequency Signal (RF) obtained from the common carotid artery
      (CCA). The method is free from fixed thresholds and uses shape fitting to get
      objective measurement. The accuracy of the algorithm was found to be better than
      5 % for software simulated and phantom arteries and better than 10 % in case of
      data obtained from CCA of human volunteers. 

PMID- 24110578
TI  - Multiobjective patient-specific estimation of a coronary circulation model for
      triple vessel disease.
AB  - Computational models can help understand the hemodynamics of the coronary
      circulation, which is of the upmost importance to help clinicians before, during
      and after a coronary artery bypass graft surgery. In this paper, we propose a
      multiobjective optimization method for parameter estimation of a computational
      model representing the coronary circulation on patients with a triple vessel
      disease. This estimation was not based on any assumption regarding the
      development of the collateral circulation, like in previous works. Indeed, the
      collateral development of a given patient is estimated through the model
      parameters. Parameter estimation was performed using clinical data from three
      patients, obtained before and during an off-pump coronary artery bypass graft
      surgery (CABG). Results showed a better performance when comparing the simulation
      with clinical data, since the total error estimation for three patients was
      reduced by 40 +/- 22%. Moreover, the proposed method provides new insight
      regarding the heterogeneous configuration of the alternative collateral vessels. 

PMID- 24110579
TI  - A model-based approach for the evaluation of vagal and sympathetic activities in
      a newborn lamb.
AB  - This paper proposes a baroreflex model and a recursive identification method to
      estimate the time-varying vagal and sympathetic contributions to heart rate
      variability during autonomic maneuvers. The baroreflex model includes
      baroreceptors, cardiovascular control center, parasympathetic and sympathetic
      pathways. The gains of the global afferent sympathetic and vagal pathways are
      identified recursively. The method has been validated on data from newborn lambs,
      which have been acquired during the application of an autonomic maneuver, without
      medication and under beta-blockers. Results show a close match between
      experimental and simulated signals under both conditions. The vagal and
      sympathetic contributions have been simulated and, as expected, it is possible to
      observe different baroreflex responses under beta-blockers compared to baseline
      conditions. 

PMID- 24110580
TI  - Computational assessment of the fractional flow reserve from intravascular
      ultrasound and coronary angiography data: a pilot study.
AB  - Cardiovascular disease is one of the primary causes of morbidity and mortality
      around the globe. Thus, the diagnosis of critical lesions in coronary arteries is
      of utmost importance in clinical practice. One useful and efficient method to
      assess the functional severity of one or multiple lesions in a coronary artery is
      the calculation of the fractional flow reserve (FFR). In the current work, we
      present a method which allows the calculation of the FFR value computationally,
      without the use of a pressure wire and the induction of hyperemia, using
      intravascular ultrasound (IVUS) and biplane angiography images for three
      dimensional (3D) coronary artery reconstruction and measurements of the
      volumetric flow rate derived from angiographic sequences. The simulated FFR
      values were compared to the invasively measured FFR values in 7 cases, presenting
      high correlation (r=0.85) and good agreement (mean difference=0.002). FFR
      assessment without employing a pressure wire and the induction of hyperemia is
      feasible using 3D reconstructed coronary artery models from angiographic and IVUS
      data coupled with computational fluid dynamics. 

PMID- 24110581
TI  - Prediction of coronary atherosclerosis progression using dynamic Bayesian
      networks.
AB  - In this paper we propose a methodology for predicting the progression of
      atherosclerosis in coronary arteries using dynamic Bayesian networks. The
      methodology takes into account patient data collected at the baseline study and
      the same data collected in the follow-up study. Our aim is to analyze all the
      different sources of information (Demographic, Clinical, Biochemical profile,
      Inflammatory markers, Treatment characteristics) in order to predict possible
      manifestations of the disease; subsequently, our purpose is twofold: i) to
      identify the key factors that dictate the progression of atherosclerosis and ii)
      based on these factors to build a model which is able to predict the progression
      of atherosclerosis for a specific patient, providing at the same time information
      about the underlying mechanism of the disease. 

PMID- 24110582
TI  - Automated Identification of fetal cardiac valve timings.
AB  - In this paper a new noninvasive method is proposed for automated estimation of
      opening and closure timings of fetal cardiac valves. These timings are obtained
      from Doppler Ultrasound (DUS) signal and fetal electrocardiogram (fECG) as a
      reference. Empirical Mode Decomposition (EMD) is first applied to the DUS signal
      to decompose it into different components called Intrinsic Mode Functions (IMFs).
      The envelope of the first IMF is then taken and its peaks are identified. The
      opening and closure of the valves are then automatically assigned to the IMF
      peaks by using Hidden Markov Model (HMM). It is shown that this new method can
      continuously evaluate fetal cardiac valves' (aortic and mitral) motion timings
      for 82.5~99.7% of cardiac cycles. The estimated timings are verified using the
      Pulsed Doppler images. These findings can be used as sensitive markers for
      evaluating the fetal cardiac performance.

PMID- 24110583
TI  - Sparse reconstruction of correlated multichannel activity.
AB  - Parametric methods for modeling sinusoidal signals with line spectra have been
      studied for decades. In general, these methods start by representing each
      sinusoidal component by means of two complex exponential functions, thereby
      doubling the number of unknown parameters. Recently, a Hankel-plus-Toeplitz
      matrix pencil method was proposed which directly models sinusoidal signals with
      discrete spectral content. Compared to its counterpart, which uses a Hankel
      matrix pencil, it halves the required number of time-domain samples and reduces
      the size of the involved linear systems. The aim of this paper is twofold.
      Firstly, to show that this Hankel-plus-Toeplitz matrix pencil also applies to
      continuous spectra. Secondly, to explore its use in the reconstruction of real
      life signals. Promising preliminary results in the reconstruction of correlated
      multichannel electroencephalographic (EEG) activity are presented. A principal
      component analysis preprocessing step is carried out to exploit the redundancy in
      the channel domain. Then the reduced signal representation is successfully
      reconstructed from fewer samples using the Hankel-plus-Toeplitz matrix pencil.
      The obtained results encourage the future development of this matrix pencil
      method along the lines of well-established spectral analysis methods. 

PMID- 24110584
TI  - Empirical mode decomposition improves detection of SSVEP.
AB  - Steady State Visual Evoked Potentials (SSVEPs) have been used to quantify
      attention-related neural activity to visual targets. This study investigates how
      empirical mode decomposition (EMD) can improve detection accuracy and rate of
      SSVEPs. First, the scalp-recorded electroencephalogram (EEG) signals are
      decomposed into intrinsic mode functions (IMFs) by EMD. Then, IMF components
      accounting for SSVEPs are selected for target frequency detection. Finally,
      target frequency is identified by two methods: Gabor transform and Canonical
      Correlation Analysis (CCA). This study quantitatively explores the impact of EMD
      on the target frequency detection. Empirical results show that the EMD improves
      their recognition accuracy when Gabor transform is used, even in a shorter
      Gaussian window, but has little effects on the performance of the CCA. Further,
      this study finds that harmonic responses of the target frequency can be used to
      enhance the SSVEP detection both for the Gabor transform and CCA. 

PMID- 24110585
TI  - Automatic Doppler signal analysis to assess utero-placental circulation for
      identifying high risk pregnancies.
AB  - High risk pregnancy conditions such as preeclampsia, pregnancy induced
      hypertension, intra-uterine growth restriction and gestational diabetes are
      associated with defective utero-placental circulation. These conditions, if
      undetected early during pregnancy, are associated with poor pregnancy outcomes
      including high morbidity/mortality for the fetus/mother. The current state of the
      art for monitoring such conditions is via (color) Doppler ultrasound with key
      clinical parameters being observed in uterine and umbilical arteries being the
      resistance index (RI), pulsatility index (PI) and AB index and early diastolic
      notching. High risk conditions in pregnancy manifest as abnormal flow profiles
      and indices in select fetal/maternal blood vessels. These parameters are gold
      standard as far as current clinical practice goes but they still suffer from low
      sensitivity in detecting and predicting the above mentioned high risk conditions
      at an earlier stage. In this paper, we propose a method based on Doppler signal
      analysis that automatically identifies the above conditions with higher
      sensitivity even when the current RI/PI indices are normal. 

PMID- 24110586
TI  - Heart sound segmentation of pediatric auscultations using wavelet analysis.
AB  - Auscultation is widely applied in clinical activity, nonetheless sound
      interpretation is dependent on clinician training and experience. Heart sound
      features such as spatial loudness, relative amplitude, murmurs, and localization
      of each component may be indicative of pathology. In this study we propose a
      segmentation algorithm to extract heart sound components (S1 and S2) based on
      it's time and frequency characteristics. This algorithm takes advantage of the
      knowledge of the heart cycle times (systolic and diastolic periods) and of the
      spectral characteristics of each component, through wavelet analysis. Data
      collected in a clinical environment, and annotated by a clinician was used to
      assess algorithm's performance. Heart sound components were correctly identified
      in 99.5% of the annotated events. S1 and S2 detection rates were 90.9% and 93.3%
      respectively. The median difference between annotated and detected events was of
      33.9 ms. 

PMID- 24110587
TI  - Electrocardiogram derived respiration from QRS slopes.
AB  - A method for estimation of respiratory rate from electrocardiogram (ECG) signals,
      based on variations in slopes of QRS complexes, is presented. 12 standard leads,
      3 leads from vectorcardiogram (VCG), and 2 additional non-standard leads derived
      from VCG loops were analysed. A total of 34 slope series were studied, 2 for each
      analysed lead: slopes between the peak of Q and R waves, and between the peak of
      R and S waves. Information of QRS slopes series was combined in order to increase
      the robustness of estimation. Evaluation is performed over a database containing
      ECG and respiratory signals simultaneously recorded in 17 subjects spontaneously
      breathing during a tilt table test. Respiratory rate estimation is performed with
      information of 4 different combinations of QRS slope series. The best results in
      respiratory rate estimation error terms are 0.72 +/- 4.34%(0.46 +/- 7.59 mHz).
      These results outperform those obtained with other known methods, motivating the
      use of QRS slopes to obtain reliable respiratory rate estimates.

PMID- 24110588
TI  - Multilevel model based glucose control for type-1 diabetes patients.
AB  - Diabetes is a disease that involves alterations at multiple biological levels,
      ranging from intracellular signalling to organ processes. Since glucose
      homeostasis is the consequence of complex interactions that involve a number of
      factors, the control of diabetes should be based on a multilevel analysis. In
      this paper, a novel approach to design of closed-loop glucose controllers based
      on multilevel models is presented. A control scheme is proposed based on
      combining a pharmacokinetic/pharmacodynamic model with an insulin signal
      transduction model for type 1 diabetes mellitus patients. Based on this, an
      insulin feedback control schemes is designed. Two main advantages of explicitly
      utilizing information at the intracellular level were obtained. First,
      significant reduction of hypoglycaemic risk by reducing the undershoot in glucose
      levels in response to added insulin. Second, robust performance for inter-patient
      changes, demonstrated through application of the multilevel control strategy to a
      well established in silico population of diabetic patients. 

PMID- 24110590
TI  - Combining pharmacological therapy and vaccination in Chronic Myeloid Leukemia via
      model predictive control.
AB  - This paper describes a simulation study which aims at optimizing the therapy for
      the control of Chronic Myeloid Leukemia according to the following objectives:
      the reduction of the administered drug and vaccine amounts, the establishment of
      a auto-immune response and the long-term control of disease without reducing the
      effective of therapy with respect to the full treatment. A therapy optimization
      method is developed defining and solving a Model Predictive Control algorithm,
      preceded by an accurate Initial Guess search based on Monte-Carlo like approach.
      Simulation results show that the suggested procedure achieves the proposed goals.

PMID- 24110589
TI  - A novel online recalibration strategy for continuous glucose measurement sensors
      employing LMI techniques.
AB  - This paper considers the problem of online calibration and recalibration of
      continuous glucose monitoring devices. A parametric relation between interstitial
      and blood glucose is investigated and a constructive algorithm to adaptively
      estimate the parameters within this relation is proposed. The algorithm
      explicitly considers measurement uncertainty of the device used to collect the
      calibration measurements and enables automatic detection of measurements which
      are not suitable to be used for calibration. The method was assessed on clinical
      data from 17 diabetic patients and the improvements with respect to the current
      state of the art is shown. 

PMID- 24110591
TI  - Tracking instantaneous pressure-to-flow dynamics of cerebral autoregulation
      induced by CO2 reactivity.
AB  - In this work, we proposed a novel method to investigate the underlying rapid
      pressure-to-flow dynamics induced by changes of arterial CO2. Autoregulation was
      modeled as a multivariate system. The instantaneous effect of CO2 to cerebral
      blood flow velocity (CBFV) was removed adaptively by the recursive least square
      (RLS) method from CBFV. The residue CBFV and arterial blood pressure (ABP) were
      then filtered by a Gaussian-modulated sinusoidal pulse filter, in order to
      optimize the time and frequency resolution when estimating the instantaneous
      phase difference between the signals using Hilbert transform (HT). The results
      indicate that the effect of CO2 on dynamic autoregulation is slower than on CBFV.

PMID- 24110592
TI  - Altered cardiovascular coupling in patients with sudden sensorineural hearing
      loss in comparison to healthy subjects.
AB  - The causes of idiopathic sudden sensorineural hearing loss (SSNHL) are still
      unclear while SSNHL seems to be a multicausal disease. To date limited
      information about autonomic regulation and, especially, cardiovascular coupling
      (CVC) are available for those patients. The objective of this study was to
      characterize short-term (30 min) CVC in 23 SSNHL patients in comparison to 23
      healthy age and gender matched normal hearing control subjects (CON). Further on,
      the results from CVC should be compared with those from standard heart rate
      variability (HRV) and blood pressure variability (BPV) analyses. The results
      showed that HRV is not affected by the disease whereas BPV analysis revealed
      significant differences between both groups (p<0.01) whereby SSNHL exhibit a
      decreased short-term BPV. Results from CVC analysis demonstrated that especially
      the applied nonlinear methods exhibit an increased short-term CVC in SSNHL
      patients (p<0.01) indicating more complex interactions of short-term HR and BP
      regulatory processes. In conclusion, this study was the first to show a changed
      and decreased short-term BPV and increased nonlinear CVC in SSNHL patients. Our
      findings might help to improve diagnostic strategies for hearing loss caused by
      vascular factors.

PMID- 24110593
TI  - Effect of respiratory-induced intensity variations on finger SpO2 measurements in
      volunteers.
AB  - Photoplethysmographic (PPG) signals were recorded from the fingers of 16 healthy
      volunteers with periods of timed and forced respiration. The aim of this pilot
      study was to compare estimations of arterial oxygen saturation (SpO2) recorded
      using a dedicated pulse oximetry system while subjects were breathing regularly
      with and without a mouthpiece containing a flow resistor. The experiments were
      designed to mimic the effects of mechanical ventilation in anesthetized patients.
      The effect of estimated airway pressures of +/- 15 cmH2O caused observable
      modulation in the recorded red and PPG signals. SpO2 values were calculated from
      the pre-recorded PPG signals. Mean SpO2 values were 95.4% with the flow resistor
      compared with 97.3% with no artificial resistance, with statistical significance
      demonstrated using a Student's t-test (P = 0.006).

PMID- 24110594
TI  - Blind Deconvolution of Hodgkin-Huxley neuronal model.
AB  - Neuron transforms information via a complex interaction between its previous
      states, its intrinsic properties, and the synaptic input it receives from other
      neurons. Inferring synaptic input of a neuron only from its membrane potential
      (output) that contains both sub-threshold and action potentials can effectively
      elucidate the information processing mechanism of a neuron. The term coined blind
      deconvolution of Hodgkin-Huxley (HH) neuronal model is defined, for the first
      time in this paper, to address the problem of reconstructing the hidden dynamics
      and synaptic input of a single neuron modeled by the HH model as well as
      estimating its intrinsic parameters only from single trace of noisy membrane
      potential. The blind deconvolution is accomplished via a recursive algorithm
      whose iterations contain running an extended Kalman filtering followed by the
      expectation maximization (EM) algorithm. The accuracy and robustness of the
      proposed algorithm have been demonstrated by our simulations. The capability of
      the proposed algorithm makes it particularly useful to understand the neural
      coding mechanism of a neuron. 

PMID- 24110595
TI  - An extended multivariate autoregressive framework for EEG-based information flow
      analysis of a brain network.
AB  - Recently effective connectivity studies have gained significant attention among
      the neuroscience community as Electroencephalography (EEG) data with a high time
      resolution can give us a wider understanding of the information flow within the
      brain. Among other tools used in effective connectivity analysis Granger
      Causality (GC) has found a prominent place. The GC analysis, based on strictly
      causal multivariate autoregressive (MVAR) models does not account for the
      instantaneous interactions among the sources. If instantaneous interactions are
      present, GC based on strictly causal MVAR will lead to erroneous conclusions on
      the underlying information flow. Thus, the work presented in this paper applies
      an extended MVAR (eMVAR) model that accounts for the zero lag interactions. We
      propose a constrained adaptive Kalman filter (CAKF) approach for the eMVAR model
      identification and demonstrate that this approach performs better than the short
      time windowing-based adaptive estimation when applied to information flow
      analysis. 

PMID- 24110596
TI  - Abnormality detection in noisy biosignals.
AB  - Although great strides have been achieved in computer-aided diagnosis (CAD)
      research, a major remaining problem is the ability to perform well under the
      presence of significant noise. In this work, we propose a mechanism to find
      instances of potential interest in time series for further analysis. Adaptive
      Kalman filters are employed in parallel among different feature axes. Lung sounds
      recorded in noisy conditions are used as an example application, with spectro
      temporal feature extraction to capture the complex variabilities in sound. We
      demonstrate that both disease indicators and distortion events can be detected,
      reducing long time series signals into a sparse set of relevant events. 

PMID- 24110597
TI  - Modification and fixed-point analysis of a Kalman filter for orientation
      estimation based on 9D inertial measurement unit data.
AB  - A common approach for high accuracy sensor fusion based on 9D inertial
      measurement unit data is Kalman filtering. State of the art floating-point filter
      algorithms differ in their computational complexity nevertheless, real-time
      operation on a low-power microcontroller at high sampling rates is not possible.
      This work presents algorithmic modifications to reduce the computational demands
      of a two-step minimum order Kalman filter. Furthermore, the required bit-width of
      a fixed-point filter version is explored. For evaluation real-world data captured
      using an Xsens MTx inertial sensor is used. Changes in computational latency and
      orientation estimation accuracy due to the proposed algorithmic modifications and
      fixed-point number representation are evaluated in detail on a variety of
      processing platforms enabling on-board processing on wearable sensor platforms. 

PMID- 24110598
TI  - Discriminative tandem features for HMM-based EEG classification.
AB  - We investigate the use of discriminative feature extractors in tandem
      configuration with generative EEG classification system. Existing studies on
      dynamic EEG classification typically use hidden Markov models (HMMs) which lack
      discriminative capability. In this paper, a linear and a non-linear classifier
      are discriminatively trained to produce complementary input features to the
      conventional HMM system. Two sets of tandem features are derived from linear
      discriminant analysis (LDA) projection output and multilayer perceptron (MLP)
      class-posterior probability, before appended to the standard autoregressive (AR)
      features. Evaluation on a two-class motor-imagery classification task shows that
      both the proposed tandem features yield consistent gains over the AR baseline,
      resulting in significant relative improvement of 6.2% and 11.2% for the LDA and
      MLP features respectively. We also explore portability of these features across
      different subjects. 

PMID- 24110599
TI  - HMM-based snorer group recognition for Sleep Apnea diagnosis.
AB  - This paper presents an Hidden Markov Models (HMM)-based snorer group recognition
      approach for Obstructive Sleep Apenea diagnosis. It models the spatio-temporal
      characteristics of different snorer groups belonging to different genders and AHI
      severity levels. The current experiment includes selecting snore data from
      subjects, identifying snorer groups based on gender and AHI values (AHI < 15 and
      AHI > 15), detecting snore episodes, MFCC computation, training and testing HMMs.
      A set of multi-level classification rules is employed for incremental diagnosis
      of OSA. The proposed method, with a relatively small data set, produces results
      nearly comparable to any existing methods with single feature class. It
      classifies snore episodes with 62.0% (male), 67.0% (female) and recognizes snorer
      group with 78.5% accuracy. The approach makes its diagnosis decision at 85.7%
      (sensitivity), 71.4% (specificity) for males and 85.7% (sensitivity and
      specificity) for females. 

PMID- 24110600
TI  - Fully automated scoring of chest radiographs in cystic fibrosis.
AB  - We present a prototype of a fully automated scoring system for chest radiographs
      (CXRs) in cystic fibrosis. The system was used to analyze real, clinical CXR
      data, to estimate the Shwachman-Kulczycki score for the image. Images were
      resampled and normalized to a standard size and intensity level, then segmented
      with a patch-based nearest-neighbor mapping algorithm. Texture features were
      calculated regionally and globally, using Tamura features, local binary patterns
      (LBP), gray-level co-occurrence matrix and Gabor filtering. Feature selection was
      guided by current understanding of the disease process, in particular the
      reorganization and thickening of airways. Combinations of these features were
      used as inputs for support vector machine (SVM) learning to classify each CXR,
      and evaluated using two-fold cross-validation for agreement with clinician
      scoring. The final computed score for each image was compared with the score
      assigned by a physician. Using this prototype system, we analyzed 139 CXRs from
      an Australian pediatric cystic fibrosis registry, for which texture
      directionality showed greatest discriminating power. Computed scores agreed with
      clinician scores in 75% of cases, and up to 90% of cases in discriminating severe
      disease from mild disease, similar to the level of human interobserver agreement
      for this dataset. 

PMID- 24110601
TI  - Emphysema classification based on embedded probabilistic PCA.
AB  - In this article we investigate the suitability of a manifold learning technique
      to classify different types of emphysema based on embedded Probabilistic PCA
      (PPCA). Our approach finds the most discriminant linear space for each emphysema
      pattern against the remaining patterns where lung CT image patches can be
      embedded. In this embedded space, we train a PPCA model for each pattern. The
      main novelty of our technique is that it is possible to compute the class
      membership posterior probability for each emphysema pattern rather than a hard
      assignment as it is typically done by other approaches. We tested our algorithm
      with six emphysema patterns using a data set of 1337 CT training patches. Using a
      10-fold cross validation experiment, an average recall rate of 69% is achieved
      when the posterior probability is greater than 75%. A quantitative comparison
      with a texture-based approach based on Local Binary Patterns and with an approach
      based on local intensity distributions shows that our method is competitive. The
      analysis of full lungs using our approach shows a good visual agreement with the
      underlying emphysema types and a smooth spatial relation. 

PMID- 24110602
TI  - Benefits of texture analysis of dual energy CT for Computer-Aided pulmonary
      embolism detection.
AB  - Pulmonary embolism is an avoidable cause of death if treated immediately but
      delays in diagnosis and treatment lead to an increased risk. Computer-assisted
      image analysis of both unenhanced and contrast-enhanced computed tomography (CT)
      have proven useful for diagnosis of pulmonary embolism. Dual energy CT provides
      additional information over the standard single energy scan by generating four
      dimensional (4D) data, in our case with 11 energy levels in 3D. In this paper a
      4D texture analysis method capable of detecting pulmonary embolism in dual energy
      CT is presented. The method uses wavelet-based visual words together with an
      automatic geodesic-based region of interest detection algorithm to characterize
      the texture properties of each lung lobe. Results show an increase in performance
      with respect to the single energy CT analysis, as well as an accuracy gain
      compared to preliminary work on a small dataset. 

PMID- 24110603
TI  - Automated measurement of skull circumference, cranial index, and braincase volume
      from pediatric computed tomography.
AB  - Normative values of pediatric skull circumference, cranial index, and braincase
      volume would inform multiple disciplines including neurosurgery, plastic surgery
      and anthropology. Semi-automated methods exist for obtaining these data but are
      time consuming and require expertise. We report on a new method for automated
      extraction of in vivo measures of pediatric crania based on x-ray computed
      tomography scans (CT). Data were obtained from a clinical image repository for
      pediatric populations in whom no pathology was noted. The automated process
      showed good agreement with semi-automated measures, although there was a small
      bias for both braincase volume and circumference. We developed an open source
      program to automatically extract measures of skull circumference, cranial index,
      and braincase volume that are likely to prove useful in multiple disciplines. 

PMID- 24110604
TI  - Measure oriented cost-sensitive SVM for 3D nodule detection.
AB  - The class imbalance issue occurs when training a computer-aided detection (CAD)
      system for nodules. This imbalance causes poor prediction performance for true
      nodules. Moreover, the misclassification costs are different between two classes
      and high sensitivity of true nodules is essential in the detection. In order to
      eliminate or reduce the false positives while keeping high sensitivity, we
      present an effective wrapper framework incorporating the evaluation measure of
      imbalanced data into the objective function of cost sensitive SVM. We improve the
      performance of classification by simultaneously optimizing the best pair of
      misclassification cost parameter, feature subset and intrinsic parameters. We
      evaluated the method on a 3D Lung nodule dataset, showing that the proposed
      method outperforms many other exiting common methods, as well as specific
      imbalanced data learning methods, which indicates the effectiveness of our method
      on the imbalanced and unequal misclassification cost data classification. 

PMID- 24110605
TI  - Adaptation of the contrast injection protocol to tube potential for
      cardiovascular computed tomography.
AB  - To investigate the adaptation of the contrast injection protocol for lower tube
      potential at cardiovascular computed tomography (CT) angiography, this study
      analyzed 83 patients (56 100kV vs. 27 120kV) imaged with a prospectively ECG
      triggered axial technique for evaluation of aortic disease on a 256-slice CT
      scanner from 4/10/12 to 5/23/12. A custom algorithm was used to select tube
      potential and tube current based on patient size. The same contrast injection
      protocol (contrast concentration 370 mgI/mL, flow rate = 3.5 mL/s, volume = 90
      mL) was applied to both cohorts. A Bae-Heiken-Brink pharmacokinetic model was
      utilized to simulate attenuation in the aorta for the applied contrast protocol
      in both cohorts and for 3 reduced volumes in the 100kV cohort (A: 72mL, -20%; B:
      60mL, -33%; C: 50mL, -44%). Quantitative analysis revealed that 100kV cohort had
      significantly higher contrast attenuation and signal-to-noise ratio than the
      120kV cohort but similar image noise. Simulation of protocol A and B in the 100kV
      cohort yielded significantly higher attenuation than that measured from the 120kV
      cohort (p<0.05); attenuation with protocol C showed no significant difference.
      Simulation results demonstrated that the amount of contrast material can be
      reduced by as much as 44% for 100 compared to 120 kV imaging but still yielded
      similar aortic attenuation. A prospective, randomized study should be conducted
      to validate the performance of the proposed contrast injection protocol at 100kV.

PMID- 24110606
TI  - An analysis-synthesis approach for neurosphere modelisation under phase-contrast
      microscopy.
AB  - The study of stem cells is one of the most important biomedical research.
      Understanding their development could allow multiple applications in regenerative
      medicine. For this purpose, automated solutions for the observation of stem cell
      development process are needed. This study introduces an on-line analysis method
      for the modelling of neurosphere evolution during the early time of their
      development under phase contrast microscopy. From the corresponding phase
      contrast time-lapse sequences, we extract information from the neurosphere using
      a combination of phase contrast physics deconvolution and curve detection for
      locate the cells inside the neurosphere. Then, based on prior biological
      knowledge, we generate possible and optimal 3-dimensional configuration using 2D
      to 3D registration methods and evolutionary optimisation algorithm. 

PMID- 24110607
TI  - Automatic prostate segmentation in cone-beam computed tomography images using
      rigid registration.
AB  - We propose to evaluate automatic three-dimensional gray-value rigid registration
      (RR) methods for prostate localization on cone-beam computed tomography (CBCT)
      scans. In total, 103 CBCT scans of 9 prostate patients have been analyzed. Each
      one was registered to the planning CT scan using different methods: (a) global
      RR, (b) pelvis bone structure RR, (c) bone RR refined by local soft-tissue RR
      using the CT clinical target volume (CTV) expanded with a 1, 3, 5, 8, 10, 12, 15
      or 20-mm margin. To evaluate results, a radiation oncologist was asked to
      manually delineate the CTV on the CBCT scans. The Dice coefficients between each
      automatic CBCT segmentation - derived from the transformation of the manual CT
      segmentation - and the manual CBCT segmentation were calculated. Global or bone
      CT/CBCT RR has been shown to yield insufficient results in average. Local RR with
      an 8-mm margin around the CTV after bone RR was found to be the best candidate
      for systematically significantly improving prostate localization. 

PMID- 24110608
TI  - Registration for frameless brain surgery based on stereo imaging.
AB  - This paper presents an implementation of stereo vision techniques to capture the
      geometric model of patient's face for registration in the frameless neurosurgery.
      A distance transform is applied on 2D CT/MRI multi-slices for on-site
      registration, further reducing requisite computation. In order to validate
      accuracy of the system, we designed a phantom to directly measure its target
      registration error (TRE). Experimental results show that the TRE is 2.72 +/-
      0.735 mm. 

PMID- 24110609
TI  - A new strategy to improve coregistration of SPECT and MR images in patients with
      high grade glioma.
AB  - This paper proposes a new strategy to optimize the coregistration of Technetium
      99m Sestamibi SPECT and MRI data in case of patients with high grade glioma. It
      consists in a personalized approach which selects, for each data set, the best
      registration method among several ones. To achieve this selection, a quantitative
      dedicated evaluation criterion based on the average intensities within specific
      anatomical structures corresponding to physiological areas of uptake of Sestamibi
      was defined. The strategy was applied to sixty-two data sets using nine
      registration methods based on mutual information and chamfer distance
      registration approaches, with different settings. It was implemented within the
      Anatomist/Brainvisa environment, using its basic registration functions. The
      visual evaluation by experts indicated that this strategy provides 60% good
      quality registrations, and 26% intermediate quality ones. Compared to the single
      use of the best global registration method, the number of registrations of good
      quality was multiplied by 1.4 when using the data specific strategy. 

PMID- 24110610
TI  - Anisotropic smoothing regularization (AnSR) in Thirion's Demons registration
      evaluates brain MRI tissue changes post-laser ablation.
AB  - MRI-guided laser-induced interstitial thermal therapy (LITT) is a form of laser
      ablation and a potential alternative to craniotomy in treating glioblastoma
      multiforme (GBM) and epilepsy patients, but its effectiveness has yet to be fully
      evaluated. One way of assessing short-term treatment of LITT is by evaluating
      changes in post-treatment MRI as a measure of response. Alignment of pre- and
      post-LITT MRI in GBM and epilepsy patients via nonrigid registration is necessary
      to detect subtle localized treatment changes on imaging, which can then be
      correlated with patient outcome. A popular deformable registration scheme in the
      context of brain imaging is Thirion's Demons algorithm, but its flexibility often
      introduces artifacts without physical significance, which has conventionally been
      corrected by Gaussian smoothing of the deformation field. In order to prevent
      such artifacts, we instead present the Anisotropic smoothing regularizer (AnSR)
      which utilizes edge-detection and denoising within the Demons framework to
      regularize the deformation field at each iteration of the registration more
      aggressively in regions of homogeneously oriented displacements while
      simultaneously regularizing less aggressively in areas containing heterogeneous
      local deformation and tissue interfaces. In contrast, the conventional Gaussian
      smoothing regularizer (GaSR) uniformly averages over the entire deformation
      field, without carefully accounting for transitions across tissue boundaries and
      local displacements in the deformation field. In this work we employ AnSR within
      the Demons algorithm and perform pairwise registration on 2D synthetic brain MRI
      with and without noise after inducing a deformation that models shrinkage of the
      target region expected from LITT. We also applied Demons with AnSR for
      registering clinical T1-weighted MRI for one epilepsy and one GBM patient pre-
      and post-LITT. Our results demonstrate that by maintaining select displacements
      in the deformation field, AnSR outperforms both GaSR and no regularizer (NoR) in
      terms of normalized sum of squared differences (NSSD) with values such as 0.743,
      0.807, and 1.000, respectively, for GBM. 

PMID- 24110611
TI  - Cardiac right ventricular segmentation via point correspondence.
AB  - This study presents an approach to the segmentation of the right ventricle (RV)
      from a sequence of cardiac magnetic resonance (MR) images. Automatic delineation
      of the RV is difficult because of its complex morphology, thin and ill-defined
      borders, and the photometric similarities between the connected cardiac regions
      such as papillary muscles and heart wall. Further, geometric/photometric models
      are hard to build from a finite training set because of the significant
      differences in size, shape, and intensity between subjects. In this study, we
      propose to use a non-rigid registration method developed recently to obtain the
      point correspondence in a sequence of cine MR images. Given the segmentation on
      the first frame, the proposed method segments both endocardial and epicardial
      borders of the RV using the obtained point correspondence, and relaxes the need
      of a training set. The proposed method is evaluated quantitatively on common data
      set by comparison with manual segmentation, which demonstrated competitive
      results in comparison with recent methods. 

PMID- 24110613
TI  - Integral invariants for image enhancement.
AB  - Medical images pose a major challenge for image analysis: often they have poor
      signal-to-noise, necessitating smoothing; yet such smoothing needs to preserve
      the boundaries of regions of interest and small features such as mammogram
      microcalcifications. We show how circular integral invariants (II) may be adapted
      for feature-preserving smoothing to facilitate segmentation. Though II is
      isotropic, we show that it leads to considerably less feature deterioration than
      Gaussian blurring and it improves segmentation of regions of interest as compared
      to anisotropic diffusion, particularly for hierarchical contour based
      segmentation methods. 

PMID- 24110612
TI  - Improving abdomen tumor low-dose CT images using dictionary learning based patch
      processing and unsharp filtering.
AB  - Reducing patient radiation dose, while maintaining a high-quality image, is a
      major challenge in Computed Tomography (CT). The purpose of this work is to
      improve abdomen tumor low-dose CT (LDCT) image quality by using a two-step
      strategy: a first patch-wise non linear processing is first applied to suppress
      the noise and artifacts, that is based on a sparsity prior in term of a learned
      dictionary, then an unsharp filtering aiming to enhance the contrast of tissues
      and compensate the contrast loss caused by the DL processing. Preliminary results
      show that the proposed method is effective in suppressing mottled noise as well
      as improving tumor detectability. 

PMID- 24110614
TI  - Isotropic anomalous filtering in Diffusion-Weighted Magnetic Resonance Imaging.
AB  - Noise is inherent to Diffusion-Weighted Magnetic Resonance Imaging (DWI) and
      noise reduction methods are necessary. Although process based on classical
      diffusion is one of the most used approaches for digital image, anomalous
      diffusion has the potential for image enhancement and it has not been tested for
      DWI noise reduction. This study evaluates Anomalous Diffusion (AD) filter as DWI
      enhancement method. The proposed method was applied to magnetic resonance
      diffusion weighted images (DW-MRI) with different noise levels. Results show
      better performance for anomalous diffusion when compared to classical diffusion
      approach. The proposed method has shown potential in DWI enhancement and can be
      an important process to improve quality in DWI for neuroimage-based diagnosis. 

PMID- 24110615
TI  - Pre-processing for muscle motion analysis: adaptive guided image filtering for
      speckle reduction of ultrasound images.
AB  - Skeletal muscle is an important tissue of human body, and its contractions
      control and regulate body motions. Muscle contraction results in morphological
      changes of the related muscles. Ultrasound imaging is an effective tool for
      studying muscle architectures and monitoring the morphological changes of
      muscles. The latter process can be realized with a motion estimation algorithm.
      However, ultrasound images are usually corrupted by speckle noises and
      performance of motion estimation methods can be significantly affected by the
      noises. To get a better performance in motion analysis, in this paper, as a pre
      processing step, an adaptive filter named adaptive guided image filtering (AGF)
      is suggested to reduce speckle noises. We first transformed the multiplicative
      noise model into an additive one by taking the logarithm of the original speckled
      data, then performed AGF to obtain the filtered image, and finally took the
      tackled image back into exponent. Experimental results showed that AGF had a
      better performance in terms of noise attenuation and edge preservation compared
      with other standard filters. In quantitative results, the filtered images also
      had the highest Peak-Signal-to-Noise Ratio (PSNR) using AGF. It's believed that
      AGF is a good choice for the pre-processing stage of muscle motion analysis. 

PMID- 24110616
TI  - Magnetic resonance image restoration via dictionary learning under spatially
      adaptive constraints.
AB  - This paper proposes a spatially adaptive constrained dictionary learning (SAC-DL)
      algorithm for Rician noise removal in magnitude magnetic resonance (MR) images.
      This algorithm explores both the strength of dictionary learning to preserve
      image structures and the robustness of local variance estimation to remove signal
      dependent Rician noise. The magnitude image is first separated into a number of
      partly overlapping image patches. The statistics of each patch are collected and
      analyzed to obtain a local noise variance. To better adapt to Rician noise, a
      correction factor is formulated with the local signal-to-noise ratio (SNR).
      Finally, the trained dictionary is used to denoise each image patch under
      spatially adaptive constraints. The proposed algorithm has been compared to the
      popular nonlocal means (NLM) filtering and unbiased NLM (UNLM) algorithm on
      simulated T1-weighted, T2-weighted and PD-weighted MR images. Our results suggest
      that the SAC-DL algorithm preserves more image structures while effectively
      removing the noise than NLM and it is also superior to UNLM at low noise levels. 

PMID- 24110617
TI  - Denoising 3D ultrasound volumes using sparse representation.
AB  - In this paper, a new 3D ultrasound (US) denoising technique that adopts the
      sparse representation has been proposed for an effective noise reduction in 3D US
      volumes. The purpose of the proposed method is to reduce image noise while
      preserving 3D objects edges, hence improving the human interpretation for
      clinical diagnosis and the 3D segmentation accuracy for further automatic
      malignancy detection. For denoising 3D US volumes, sparse representation was
      employed, which has showed an excellent performance in reducing Gaussian noise.
      It has been well known that US images contain severe multiplicative speckle
      noise, which has different characteristics compared to the additive Gaussian
      noise. In this paper, we propose a denoising framework for effectively reducing
      both Gaussian noise and speckle noise on 3D US volumes. The proposed method
      removes Gaussian noise using sparse representation. Then, a logarithmic transform
      is performed to transform the speckle noise into Gaussian noise for applying the
      sparse representation. To demonstrate the effectiveness of the proposed denoising
      method, comparative and quantitative experiments had been conducted on a
      synthesized 3D US phantom data. Experimental results showed that the proposed
      denoising could improve image quality in terms of denoising measurements. 

PMID- 24110618
TI  - Implantable acceleration plethysmography for blood pressure determination.
AB  - This paper presents an implantable accelerometer which detects plethysmograms
      directly at an artery. The sensor provides a new method for continuous blood
      pressure monitoring. In vivo measurements indicate that the accelerometer is well
      suited for determining the Pulse Transit Time (PTT) and the Reflected Wave
      Transit Time (RWTT). Both parameters show a high correlation with the systolic
      blood pressure. By varying the blood pressure, it was seen that RWTT more closely
      agrees with theory than PTT. Through several blood pressure sweeps the RWTT, as
      detected by the accelerometer, coincided very well with the systolic blood
      pressure, with a correlation coefficient of 0.96 and mean deviation of 4.3% for
      1800 pulses. 

PMID- 24110619
TI  - Development and testing of an artificial arterial and venous pulse oximeter.
AB  - The monitoring of patients healthcare is of a prime importance to ensure their
      efficient and effective treatment. Monitoring blood oxygen saturation is a field
      which has grown significantly in recent times and more specifically in tissues
      affected by diseases or conditions that may negatively affect the function of the
      tissue. This study involved the development and testing of a highly sensitive non
      invasive blood oxygen saturation monitoring device. A device that can be used to
      continuously monitor the condition of tissue affected by diseases which affect
      the blood flow through the tissue, and the oxygen usage in tissue. The device's
      system was designed to specifically monitor occluded tissue which has low oxygen
      saturations and low perfusion. Although with limitted validation the system was
      unable to accurately measure the venous oxygenation specifically, but it was able
      to measure the mixed oxygen saturation. With further research it would be
      possible to validate the system for measuring both the arterial and venous oxygen
      saturations.

PMID- 24110620
TI  - Free flap pulse oximetry utilizing reflectance photoplethysmography.
AB  - The successful salvage of a free flap is dependent on the continuous monitoring
      of perfusion. To date there is no widely accepted and readily available post
      operative monitoring technique to reliably assess the viability of free flaps by
      continuously monitoring free flap blood oxygen saturation. In an attempt to
      overcome the limitations of the current techniques a reflectance
      photoplethysmographic (PPG) processing system has been developed with the
      capability of real-time estimation of arterial oxygen saturation (SpO2) levels
      implemented in LabVIEW. This system was evaluated in clinical measurements on
      five patients undergoing breast reconstruction using Deep Inferior Epigastric
      Perforator (DIEP) flap. Good quality PPG signals were obtained from the flaps and
      fingers simultaneously. The estimated free flap SpO2 values were in broad
      agreement with the oxygen saturation readings from the commercial pulse oximeter.
      The results suggest that reflectance free flap photoplethysmography can be used
      as a continuous monitoring technique to non-invasively monitor the perfusion of
      free flaps. 

PMID- 24110621
TI  - A wideband scalar network analyzer for biomedical dehydration measurements.
AB  - This paper presents a wideband microwave approach towards biomedical dehydration
      monitoring. The introduced concept is verified via invasive measurements on
      several blood samples. A microwave measurement circuit, based of a two-port
      scalar vector network analyzer is presented. The circuit operates between 5GHz
      and 20GHz using a planar permittivity sensor. Measurements of all subcomponents
      are shown together with measurements of a Water-NaCl-Glycerol solution. 

PMID- 24110622
TI  - ARTSENS - an image-free system for noninvasive evaluation of arterial compliance.
AB  - Evaluation of arterial compliance is significant in cardiovascular diagnosis for
      early detection of coronary heart disease. We present ARTSENS, an image-free
      system for non-invasive evaluation of arterial compliance in-vivo. The system
      utilizes a single element ultrasound probe with intelligent measurement
      algorithms to ensure accurate evaluation of local arterial compliance without an
      image. The ability of the system to detect artery anatomy and measure compliance
      was verified by in-vivo measurements conducted on 106 subjects. The accuracy of
      compliance estimates were evaluated by comparison with a state of art imaging
      system. The measurements made using ARTSENS showed strong correlation with those
      made using the imaging system. The ability of ARTSENS to detect age-related
      trends in arterial compliance was also investigated. 

PMID- 24110623
TI  - Ambulatory respiratory rate detection using ECG and a triaxial accelerometer.
AB  - Continuous monitoring of respiratory rate in ambulatory conditions has widespread
      applications for screening of respiratory diseases and remote patient monitoring.
      Unfortunately, minimally obtrusive techniques often suffer from low accuracy. In
      this paper, we describe an algorithm with low computational complexity for
      combining multiple respiratory measurements to estimate breathing rate from an
      unobtrusive chest patch sensor. Respiratory rates derived from the respiratory
      sinus arrhythmia (RSA) and modulation of the QRS amplitude of electrocardiography
      (ECG) are combined with a respiratory rate derived from tri-axial accelerometer
      data. The three respiration rates are combined by a weighted average using
      weights based on quality metrics for each signal. The algorithm was evaluated on
      15 elderly subjects who performed spontaneous and metronome breathing as well as
      a variety of activities of daily living (ADLs). When compared to a reference
      device, the mean absolute error was 1.02 breaths per minute (BrPM) during
      metronome breathing, 1.67 BrPM during spontaneous breathing, and 2.03 BrPM during
      ADLs. 

PMID- 24110624
TI  - Support vector-based Takagi-Sugeno fuzzy system for the prediction of binding
      affinity of peptides.
AB  - High dimensional, complex and non-linear nature of the post-genome data often
      adversely affects the performance of predictive models. There are two methods
      that have been widely used to model such non-linear systems, namely Fuzzy System
      (FS) and Support Vector Machine (SVM). FS is good at modelling uncertainty and
      yielding a set of interpretable IF-THEN rules, but suffers from the curse of
      dimensionality whereas SVM is a method that has been shown to effectively deal
      with large number of dimensions leading to better generalization ability. In this
      paper, a hybrid system is therefore proposed to improve FS with the aid of SVM
      based regression method and successfully applied to the prediction of binding
      affinity of peptides, which is regarded as one of the most complex modelling
      problems in the post-genome era due to the diversity of peptides discovered. The
      proposed hybrid method yields comparatively better results than what has been
      presented in the recently published papers, therefore can also be considered for
      other bioinformatics applications. 

PMID- 24110625
TI  - Construction of protein distance matrix based on amino acid indices and Discrete
      Fourier Transform.
AB  - Protein distance matrix is widely used in various protein sequence analyses, and
      mainly obtained by using pairwise sequence alignment scores or protein sequence
      homology, which fail to take into consideration of individual physical
      characteristics of protein sequences and amino acids, or a combination of these
      features. In this paper, a new method is therefore proposed for constructing
      protein distance matrix based on natural amino acid indices in combination with
      Discrete Fourier Transform (DFT). For the proposed method, protein distance
      matrices can be generated using any given set of amino acid indices, each one of
      which represents a unique biological feature of protein sequences. In this study,
      the results are based on the combination of 25 widely accepted amino acid
      indices, which produced the best results, according to the biological
      relationships between proteins. As a case study 26 Cluster of Differentiation 4
      (CD4) protein sequences were used in order to construct a distance matrix based
      on the proposed method. The results show that the pairwise relationship between
      CD4 protein sequences remain the same in comparison with their pairwise percent
      identity. For another group of protein sequences the pairwise relationship
      between CD4 protein sequences dramatically changed with the proposed method in
      comparison to the pairwise percent identity. The proposed distance matrix has
      been shown to have a positive impact on these case studies and therefore is
      expected to be useful in several fields such as multiple protein sequence
      alignment and phylogenetic analysis, where an accurate distance matrix based on
      natural generalized protein properties plays an important role.

PMID- 24110626
TI  - Segmentation of MR images by using grow and learn network on FPGAs.
AB  - Image segmentation is one of the mostly used procedures in the medical image
      processing applications. Due to the high resolution characteristics of the
      medical images and a large amount of computational load in mathematical methods,
      medical image segmentation process has an excessive computational complexity.
      Recently, FPGA implementation has been applied in many areas due to its parallel
      processing capability. In this study, neighbor-pixel-intensity based method for
      feature extraction and Grow and Learn (GAL) network for segmentation process are
      proposed. The proposed method is comparatively examined on both PC and FPGA
      platforms. 

PMID- 24110627
TI  - A framework towards computational discovery of disease sub-types and associated
      (sub-)biomarkers.
AB  - Biomarker related patient data is generally assessed in order to determine
      relevant but generalized subset of the biomarkers. However, it fails to identify
      specific sub-groups of the patients or their corresponding (subset of) the
      biomarkers. This paper therefore proposes a novel framework that is capable of
      discovering disease sub-groups (types) and associated subset of biomarkers, which
      is expected to lead to enable the discovery of personalized bio-marker set. The
      framework is based on the utilization of a histogram obtained by using the
      Euclidean distances between the samples in a given data set. The t-test method is
      used for the selection of sub-set(s) of the biomarkers whereas the classification
      is performed by means of k-nearest neighbor, support vector machines and naive
      Bayes (NBayes) classifiers. For the assessment of the methods, leave-out-out
      cross validation is employed. As a case study, the method is applied in the
      analysis of male hypertension microarray data that consists of 159 patients and
      22184 gene expressions. The method has helped identify specific sub-groups of the
      patients and their corresponding bio-marker sub-sets. The results therefore
      suggest that the generalized bio-marker sub-sets are not representative of the
      disease and therefore more focus should be on the sub-groups of the patients and
      their biomarker subsets identified through the proposed approach. It is
      particularly observed that the threshold values over the histogram are crucial to
      discover both sub-sets of the samples and biomarkers, and therefore can be used
      to determine complexity level of the study. 

PMID- 24110628
TI  - Effect of large arteries on blood pressure variability.
AB  - Blood pressure (BP) variability is generally considered to be due to neurogenic
      influences on arterioles modulating peripheral resistance, as well as variations
      in stroke volume (SV). However, for a given change in peripheral resistance or
      SV, the degree of BP variability is modulated by the stiffness of large conduit
      arteries. Recent epidemiological evidence shows that cardiovascular risk is not
      only related to the average arterial pressure, but also to the degree of diurnal
      variability. In addition, short-term variability has been shown to be related to
      aortic stiffness measured as pulse wave velocity, a strong independent predictor
      of cardiovascular risk. This study addresses the relation between large artery
      stiffness and BP variability using a lumped parameter model of the systemic
      circulation described by total arterial compliance, total peripheral resistance
      (TPR) and aortic characteristic impedance. The variability in TPR is simulated
      using a random function with a Gaussian distribution and changes in arterial
      stiffness are simulated by variation in compliance, where compliance is either
      linear (pressure independent) or nonlinear (pressure dependent). Simulation
      results show that (i) BP variability is greater when due to changes in TPR
      compared to similar relative changes in SV, (ii) pressure dependency of arterial
      stiffness results in a curvilinear relation between systolic BP variability and
      mean arterial pressure (MAP), such that a critical mean pressure (MAPc) exists
      for minimal BP variability, (iii) increase in arterial stiffness (as occurs with
      aging) result in a higher MAPc for minimal BP variability, or increased BP
      variability at older age for similar values of MAP. These findings suggest that
      interventions aimed at reducing BP variability will need to consider large artery
      stiffness for optimal efficacy. 

PMID- 24110629
TI  - An initial step towards improving the accuracy of the oscillometric blood
      pressure measurement.
AB  - We conceived a set of physical model-based techniques to compute blood pressure
      (BP) from a standard oscillometric cuff pressure measurement. First, the cuff
      pressure measurement is represented with a physical model. Then, the model
      unknowns are determined from the measurement via a parametric, non-parametric or
      hybrid technique. Finally, the entire BP waveform is computed from the determined
      model. For an initial assessment, we compared the accuracy of these techniques
      with the conventional fixed-ratio technique for computing systolic and diastolic
      pressures using cuff pressure measurements simulated with an established
      oscillometric model over a wide parameter range. The new techniques afforded much
      greater accuracy than the conventional technique. Our future efforts will focus
      on experimental validation. 

PMID- 24110630
TI  - Risk analysis and detection of thrombosis by measurement of electrical
      resistivity of blood.
AB  - Monitoring of thrombogenic process is very important in ventricular assistance
      devices (VADs) used as temporary or permanent measures in patients with advanced
      heart failure. Currently, there is a lack of a system which can perform a real
      time monitoring of thrombogenic activity. Electrical signals vary according to
      the change in concentration of coagulation factors as well as the distribution of
      blood cells, and thus have potential to detect the thrombogenic process in an
      early stage. In the present work, we have made an assessment of an
      instrumentation system exploiting the electrical properties of blood. The
      experiments were conducted using bovine blood. Electrical resistance tomography
      with eight-electrode sensor was used to monitor the spatio-temporal change in
      electrical resistivity of blood in thrombogenic and non-thrombogenic condition.
      Under non-thrombogenic condition, the resistivity was uniform across the cross
      section and average resistivity monotonically decreased with time before
      remaining almost flat. In contrary, under thrombogenic condition, there was non
      uniform distribution across the cross-section, and average resistivity fluctuated
      with time. 

PMID- 24110631
TI  - Noninvasive blood-flow meter using a curved cannula with zero compensation for an
      axial flow blood pump.
AB  - In order to monitor the condition of a patient using a left ventricular assist
      system (LVAS), blood flow should be measured. However, the reliable determination
      of blood-flow rate has not been established. The purpose of the present study is
      to develop a noninvasive blood-flow meter using a curved cannula with zero
      compensation for an axial flow blood pump. The flow meter uses the centrifugal
      force generated by the flow rate in the curved cannula. Two strain gauges served
      as sensors. The first gauges were attached to the curved area to measure static
      pressure and centrifugal force, and the second gauges were attached to straight
      area to measure static pressure. The flow rate was determined by the differences
      in output from the two gauges. The zero compensation was constructed based on the
      consideration that the flow rate could be estimated during the initial driving
      condition and the ventricular suction condition without using the flow meter. A
      mock circulation loop was constructed in order to evaluate the measurement
      performance of the developed flow meter with zero compensation. As a result, the
      zero compensation worked effectively for the initial calibration and the zero
      drift of the measured flow rate. We confirmed that the developed flow meter using
      a curved cannula with zero compensation was able to accurately measure the flow
      rate continuously and noninvasively. 

PMID- 24110632
TI  - Computational simulation to understand vision changes during prolonged
      weightlessness.
AB  - A mathematical model of whole body and cerebral hemodynamics is a useful tool for
      investigating visual impairment and intracranial pressure (VIIP), a recently
      described condition associated with space flight. VIIP involves loss of visual
      acuity, anatomical changes to the eye, and, usually, elevated cerebrospinal fluid
      pressure. Loss of visual acuity is a significant threat to astronaut health and
      performance. It is therefore important to understand the pathogenesis of VIIP.
      Some of the experimental measurements that could lead to better understanding of
      the pathophysiology are impossible or infeasible on orbit. A computational
      implementation of a mathematical model of hypothetical pathophysiological
      processes is therefore valuable. Such a model is developed, and is used to
      investigate how changes in vascular compliance or pressure can influence
      intraocular or intracranial pressure. 

PMID- 24110633
TI  - Wearable PWV technologies to measure Blood Pressure: eliminating brachial cuffs.
AB  - The clinical demand for technologies to monitor Blood Pressure (BP) in ambulatory
      scenarios with minimal use of inflation cuffs is strong: new generation of BP
      monitors are expected to be not only accurate, but also non-occlusive. In this
      paper we review recent advances on the use of the so-called Pulse Wave Velocity
      (PWV) technologies to estimate BP in a beat-by-beat basis. After introducing the
      working principle and underlying methodological limitations, two implementation
      examples are provided. Pilot studies have demonstrated that novel PWV-based BP
      monitors depict accuracy scores falling within the limits of the British
      Hypertensive Society (BHS) Grade A standard. The reported techniques pave the way
      towards ambulatory-compliant, continuous and non-occlusive BP monitoring devices,
      where the use of inflation cuffs is drastically reduced. 

PMID- 24110634
TI  - CMOS capacitive biosensors for highly sensitive biosensing applications.
AB  - Magnetic microbeads are widely used in biotechnology and biomedical research for
      manipulation and detection of cells and biomolecules. Most lab-on-chip systems
      capable of performing manipulation and detection require external instruments to
      perform one of the functions, leading to increased size and cost. This work aims
      at developing an integrated platform to perform these two functions by
      implementing electromagnetic microcoils and capacitive biosensors on a CMOS
      (complementary metal oxide semiconductor) chip. Compared to most magnetic-type
      sensors, our detection method requires no externally applied magnetic fields and
      the associated fabrication is less complicated. In our experiment, microbeads
      coated with streptavidin were driven to the sensors located in the center of
      microcoils with functionalized anti-streptavidin antibody. Detection of a single
      microbead was successfully demonstrated using a capacitance-to-frequency readout.
      The average capacitance changes for the experimental and control groups were -5.3
      fF and -0.2 fF, respectively. 

PMID- 24110635
TI  - Detection of RNAP-DNA complexes using solid state nanopores.
AB  - Transcription is the first step in gene expression where DNA is copied into RNA.
      It is extensively studied at the bulk level especially the regulation mechanism,
      which in cancerous cells is impaired. We were interested in studying E. coli RNAP
      enzyme at the single-molecule level for its functional as well as molecular motor
      properties. With nanopore sensing, we were able to observe RNA polymerase-DNA
      complexes translocate through nanopores and able to distinguish between
      individual complexes and bare RNA polymerase. We were also able to observe
      orientation of RNA polymerase in the nanopore whether flow or electric field
      predominates. The complexity of the signals from the protein-DNA complexes
      experiment motivated us to develop level detection software. This software is
      based on a change detection method called the CUSUM algorithm. OpenNanpore
      software was designed to analyze in details current blockages in nanopore signals
      with very little prior knowledge on the signal. With this work one can separate
      events according to their number of levels and study those sub-populations
      separately. 

PMID- 24110636
TI  - Temporal resolution of nanopore sensor recordings.
AB  - Here we discuss the limits to temporal resolution in nanopore sensor recordings,
      which arise from considerations of both small-signal frequency response and
      accumulated noise power. Nanopore sensors have strong similarities to patch-clamp
      ion channel recordings, except that the magnitudes of many physical parameters
      are substantially different. We will present examples from our recent work
      developing high-speed nanopore sensing platforms, in which we physically
      integrated nanopores with custom low-noise complementary metal-oxide
      semiconductor (CMOS) circuitry. Close physical proximity of the sensor and
      amplifier electronics can reduce parasitic capacitances, improving both the
      signal-to-noise ratio and the effective temporal resolution of the recordings. 

PMID- 24110637
TI  - Physical stability of cholesterol derivatives combined with liposomes and their
      in vitro behavior.
AB  - The purpose of this study was to investigate the physical stability and drug
      release of two cholesterol derivatives (4-cholesterocarbonyl-4'-(N,N,N
      triethylamine butyloxyl bromide, CTBBA, and 4-cholesterocarbonyl-4'-(N,N'
      diethylamino-butyloxy, CDBA), when combined with doxorubicin (DOX)-loaded
      liposomes in vitro. CTBBA-liposome revealed a positive charge at a pH between 3
      and 10, as indicated by the zeta-potential. DOX-encapsulated CTBBA-liposomes
      possessed better physical stability both in PBS and in fetal bovine serum (FBS)
      added to PBS. 

PMID- 24110638
TI  - Engineered virus-like nanoparticle heparin antagonists.
AB  - Virus nanoparticles provide a self-assembling, reproducible multivalent platform
      that can be chemically and genetically manipulated for the presentation of a wide
      array of epitopes. Presented herein are engineered bacteriophage Qbeta
      nanoparticles that function as potent heparin antagonists. Three successful
      approaches have been used: 1) chemically appending poly-Arg peptides; 2) point
      mutations to Arg on the virus capsid; 3) incorporation of heparin-binding
      peptides displayed externally on the virus surface. Each approach generates
      particles with good heparin antagonist activity with none of the toxic side
      effects of protamine, the only drug currently FDA-approved for clinical use as a
      heparin antagonist. 

PMID- 24110639
TI  - Effects of low level light irradiation on the migration of mesenchymal stem cells
      derived from rat bone marrow.
AB  - Low level light irradiation (LLLI) was found to exert positive effects on various
      cells in vitro. The aim of this study was to investigate the effect of LLLI on
      the migration of rat bone marrow mesenchymal stem cells (rbMSCs). Light
      irradiation was applied at the energy density of 4 J/cm(2) using red (630 nm) and
      near infrared (NIR, 850 nm) light emitting diodes (LEDs). Wound healing assay
      showed both red and NIR light irradiation increased cell mobility. Red and NIR
      light enhanced transmembrane migration of rbMSCs up to 292.9% and 263.6%
      accordingly. This agreed with enzymatic activities of MMP-2 and MMP-9 enhanced by
      irradiation. F-actin accumulation and distribution correlated to increased
      migration in light-irradiated MSCs. Reactive oxygen species production as well as
      the expression of pFAK and pNF-kB were elevated after red and NIR LLLI. The study
      demonstrated that red and NIR LLLI increased rbMSCs migration and identified the
      phosphorylation of FAK and NF-kB as critical steps for the elevated cell
      migration upon LLLI. 

PMID- 24110640
TI  - Modeling of animal movement by AR process and effect of predictability of the
      behavior on perception of animacy and intentionality.
AB  - We perceive animacy even on a simple dot traveling across a screen based on its
      movements. Research studies have pointed out several features of movement that
      are assumed to induce the perception of animacy; however, validations and
      discussions about these features are still insufficient. Meanwhile, other studies
      indicate that the perception of the intentionality is a prerequisite for the
      perception of animacy but these perceptions have not been differentiated clearly
      in the literature. In this study, we conduct an experiment with human
      participants to clarify the differences between animacy and intentionality in
      terms of the predictability of behavior. First, we model the behavior of goldfish
      using an autoregressive process and create several types of movies of a white dot
      moving on a black background where we change the fluctuation levels of its
      velocity and its rotation. The movies are presented to human participants and
      they are asked to chase the white dot using a pen tablet so that the
      predictability of the behavior can be quantified. The participants are also asked
      to rate the animacy and the intentionality of the moving dot. Our results reveal
      a negative correlation between the perception of animacy and intentionality. 

PMID- 24110641
TI  - Changes in EMG latencies during balance therapy using enhanced virtual reality
      with haptic floor.
AB  - In the paper a research on enhanced experience of virtual reality supported
      balance training is presented. Haptic floor, mounted on the dynamic standing
      frame was used as a biofeedback at collisions in virtual environment.
      Electromyographic muscle activity of soleus, gastrocnemius, tibialis anterior,
      semimembranosus, rectus femoris, tensor fasciae latae and erector spinae at the
      time of onset and recovery of postural perturbation were monitored using surface
      electrodes. 12 neurologically intact young adults participated in the research
      study. The main goal was to identify the differences in postural response
      strategies at collisions in the virtual world w/o haptic feedback. We found more
      dynamic responses in all subjects when applying haptic floor, especially in the
      ankle complex, stabilizing the tibia at the onset of perturbation. Choosing
      different strategies using the haptic floor may significantly enhance the
      telerehabilitation experience and thus increase the effectivness of the tele
      balance training. Besides telerehabilitation, such system may be also effective
      for postural reponse assessment and thus simplified telediagnostics. However, the
      findings call for further study to support the proposed proof of concept. 

PMID- 24110642
TI  - Haptic training for a visuomotor fetch & pursue task.
AB  - Can haptic interaction improve the tracking performance in a fetch & pursue task,
      similar to clay pigeon shooting? In order to answer this question, we challenged
      the tracking movements of the subjects by a saddle-like moving force field, with
      the unstable manifold aligned along the moving target and the stable manifold
      orthogonal to it. The experimental results show a positive effect, suggesting
      that the internal model acquired by the subjects for compensating the target
      linked haptic disturbance can improve the prediction capability of the subjects
      based on pure visuo-motor feedback. 

PMID- 24110643
TI  - Haptic fMRI: combining functional neuroimaging with haptics for studying the
      brain's motor control representation.
AB  - A challenging problem in motor control neuroimaging studies is the inability to
      perform complex human motor tasks given the Magnetic Resonance Imaging (MRI)
      scanner's disruptive magnetic fields and confined workspace. In this paper, we
      propose a novel experimental platform that combines Functional MRI (fMRI)
      neuroimaging, haptic virtual simulation environments, and an fMRI-compatible
      haptic device for real-time haptic interaction across the scanner workspace
      (above torso ~ .65*.40*.20m(3)). We implement this Haptic fMRI platform with a
      novel haptic device, the Haptic fMRI Interface (HFI), and demonstrate its
      suitability for motor neuroimaging studies. HFI has three degrees-of-freedom
      (DOF), uses electromagnetic motors to enable high-fidelity haptic rendering
      (>350Hz), integrates radio frequency (RF) shields to prevent electromagnetic
      interference with fMRI (temporal SNR >100), and is kinematically designed to
      minimize currents induced by the MRI scanner's magnetic field during motor
      displacement (<2cm). HFI possesses uniform inertial and force transmission
      properties across the workspace, and has low friction (.05-.30N). HFI's RF noise
      levels, in addition, are within a 3 Tesla fMRI scanner's baseline noise variation
      (~.85+/-.1%). Finally, HFI is haptically transparent and does not interfere with
      human motor tasks (tested for .4m reaches). By allowing fMRI experiments
      involving complex three-dimensional manipulation with haptic interaction, Haptic
      fMRI enables-for the first time-non-invasive neuroscience experiments involving
      interactive motor tasks, object manipulation, tactile perception, and visuo-motor
      integration. 

PMID- 24110644
TI  - Haptic perception of multi-joint hypertonia during simulated patient-therapist
      physical tele-interaction.
AB  - A potential solution to provide individualized physical therapy in remote areas
      is tele-interaction via robotic devices. To maintain stability during tele
      interaction, transmission delay-compensation algorithms bound the impedance
      between the patient and the therapist. This can compromise the haptic perception
      of the patient being assessed, which can in turn lead to a bad diagnosis or
      intervention. We investigated how the perception of the severity of hypertonia (a
      common condition after neurological disorders) varied by modifying the connection
      impedance on a physical simulator. We found that assessing hypetonia using a low
      impedance connection may result in an overestimation of mild impairments. 

PMID- 24110645
TI  - Robot hand with soft tactile sensors and underactuated control.
AB  - We developed a robot hand with three fingers and controlled them using
      underactuated control to obtain a more flexible grip. With underactuated control,
      we can flexibly operate an artificial robot hand and reduce the number of
      actuators. The robot fingers had three joints to imitate human fingers. One
      finger was driven by one wire and one servo motor for bending and by three
      torsion springs for extension. We also developed a soft tactile sensor having
      three pneumatic sensors and mounted it on front of each robot fingers. We
      obtained the following information from our experimental examinations of the
      robot hand. It adaptively grasped an object by underactuated control. The soft
      tactile sensor deftly touched an object, and the data showed the contact position
      with. By analyzing the data from tactile sensors, we obtained the rough
      information of the object's shape. 

PMID- 24110646
TI  - Evaluation of the Microsoft Kinect for screening ACL injury.
AB  - A study was conducted to evaluate the use of the skeletal model generated by the
      Microsoft Kinect SDK in capturing four biomechanical measures during the Drop
      Vertical Jump test. These measures, which include: knee valgus motion from
      initial contact to peak flexion, frontal plane knee angle at initial contact,
      frontal plane knee angle at peak flexion, and knee-to-ankle separation ratio at
      peak flexion, have proven to be useful in screening for future knee anterior
      cruciate ligament (ACL) injuries among female athletes. A marker-based Vicon
      motion capture system was used for ground truth. Results indicate that the Kinect
      skeletal model likely has acceptable accuracy for use as part of a screening tool
      to identify elevated risk for ACL injury. 

PMID- 24110647
TI  - VCSEL based, wearable, continuously monitoring pulse oximeter.
AB  - We present the development of a novel pulse oximeter based on low power, low
      cost, Vertical Cavity Surface Emitting Laser (VCSEL) technology. This new design
      will help address a need to perform regular measurements of pulse oximetry for
      patients with chronic obstructive pulmonary disease. VCSELs with wavelengths
      suitable for pulse oximetry were developed and packaged in a PLCC package for a
      low cost solution that is easy to integrate into a pulse oximeter design. The
      VCSELs were integrated into a prototype pulse oximeter that is unobtrusive and
      suitable for long term wearable use. The prototype achieved good performance
      compared the Nonin Onyx II pulse oximeter at less than one fifth the weight in a
      design that can be worn behind the ear like a hearing aid. 

PMID- 24110648
TI  - Contact pressure monitoring device for sleep studies.
AB  - This project implements a non-invasive sleep monitoring system using a bed
      pressure sensor array. The system detects changes in the contact pressure between
      a subject and the bed and is able to automatically select the sensor with the
      best respiratory signal, determine the respiratory rate (RR), count number of
      sleep apneas and count body position changes through the night. The respiratory
      signal is validated with an airflow sensor using Pearson's correlation
      coefficient. To determine the performance of body position and apnea detection
      algorithms, the sensibility and positive predictivity is computed on preliminary
      data and known records from a Physionet database. Real data is obtained from 5
      subjects totaling 39 hours measured at home during a full night sleep, in a non
      invasive way. The data is used to calculate relevant parameters to estimate a
      sleep quality. Cumulative frequency of sleep interval duration is proposed as a
      novel metric for sleep assessment. 

PMID- 24110649
TI  - Quantitative classification of tumor cell morphological changes on selectively
      functionalized biochips.
AB  - Proteomics information of cancer has shown that abnormalities at the levels of
      growth factors, receptors, intracellular mediators and transcription factors play
      major role in the disease progression. We report a directly quantifiable approach
      to measure tumor cell behavior on functionalized chips. The chips were
      functionalized with aptamer molecules that were selective against epidermal
      growth factor receptor (EGFR), a commonly overexpressed cancer biomarker. The
      chip-bound aptamer selectively isolated tumor cells from cell mixture samples.
      The isolated cells were thus bound to the chip surface. However, some normal
      cells also got captured on the surface. The selectivity and sensitivity of tumor
      isolation changed when the surface of the chip was chemically treated to create
      nanoscale texture. The captured cancer cells showed distinctly different behavior
      on the surface of the chip than that for the normal cells. The behavior
      quantification can serve as a novel modality to detect cancer cells from simple
      samples like blood, saliva or urine. 

PMID- 24110650
TI  - Development of a point-of-care medical device to measure head impact in contact
      sports.
AB  - This paper presents a prototype of a wireless, point-of-care medical device to
      measure head impacts in contact or collision sports. The device is currently
      capable of measuring linear acceleration, time, and the duration of impact. The
      location of the impact can also be recorded by scaling the prototype design to
      multiple devices. An experimental apparatus was built to simulate head impacts
      and to verify the data from the device. Preliminary results show that the
      biomechanical measures from the device are sufficiently accurate. 

PMID- 24110651
TI  - Point-of-Care device for quantification of zinc in serum.
AB  - With 42,000 cases reported annually in the United States and an approximate 10%
      mortality rate, [1] pediatric septic shock is a major health problem that is
      often difficult to treat effectively. Several studies have shown that children
      experiencing pediatric septic shock often have critically low levels of serum
      zinc (Zn), suggesting supplementation of Zn to be an effective therapeutic
      strategy. However, to protect the safety and well-being of the patient, it is
      extremely important to monitor blood serum concentration of Zn during
      supplementation in order to ensure that levels remain at or near the
      physiological norm and thus minimize the risk of heavy metal toxicity from over
      supplementation. Current methods for quantifying Zn in serum typically require
      sending serum samples to external laboratory facilities resulting in turnaround
      times ranging from hours to a few days. Therefore, timely monitoring of Zn levels
      in serum is often not possible in the clinical setting which ultimately limits
      the ability to use Zn supplementation as a therapeutic intervention. This paper
      reports on the development of a Point-of-Care device for rapid electrochemical
      measurement of Zn in serum. The device is centered on a three electrode sensor
      which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The Cu based
      sensor is read using a reader that has been developed using commercially
      available embedded system parts in combination with custom analog circuitry that
      is able to produce quantification results in approximately 6 minutes. 

PMID- 24110652
TI  - Integration of drug dosing data with physiological data streams using a cloud
      computing paradigm.
AB  - Many drugs are used during the provision of intensive care for the preterm
      newborn infant. Recommendations for drug dosing in newborns depend upon data from
      population based pharmacokinetic research. There is a need to be able to modify
      drug dosing in response to the preterm infant's response to the standard dosing
      recommendations. The real-time integration of physiological data with drug dosing
      data would facilitate individualised drug dosing for these immature infants. This
      paper proposes the use of a novel computational framework that employs real-time,
      temporal data analysis for this task. Deployment of the framework within the
      cloud computing paradigm will enable widespread distribution of individualized
      drug dosing for newborn infants. 

PMID- 24110653
TI  - Applying secret sharing for HIS backup exchange.
AB  - To secure business continuity is indispensable for hospitals to fulfill its
      social responsibility under disasters. Although to back up the data of the
      hospital information system (HIS) at multiple remote sites is a key strategy of
      business continuity plan (BCP), the requirements to treat privacy sensitive data
      jack up the cost for the backup. The secret sharing is a method to split an
      original secret message up so that each individual piece is meaningless, but
      putting sufficient number of pieces together to reveal the original message. The
      secret sharing method eases us to exchange HIS backups between multiple
      hospitals. This paper evaluated the feasibility of the commercial secret sharing
      solution for HIS backup through several simulations. The result shows that the
      commercial solution is feasible to realize reasonable HIS backup exchange
      platform when template of contract between participating hospitals is ready. 

PMID- 24110654
TI  - Data processing and presentation for a personalised, image-driven medical
      graphical avatar.
AB  - With the continuing digital revolution in the healthcare industry, patients are
      being confronted with the difficult task of managing their digital medical data.
      Current personal health record (PHR) systems are able to store and consolidate
      this data, but they are limited in providing tools to facilitate patients'
      understanding and management of the data. One reason for this stems from the
      limited use of contextual information, especially in presenting spatial details
      such as in volumetric images and videos, as well as time-based temporal data.
      Further, lack of meaningful visualisation techniques exist to represent the data
      stored in PHRs. In this paper we propose a medical graphical avatar (MGA)
      constructed from whole-body patient images, and a navigable timeline of the
      patient's medical records. A data mapping framework is presented that extracts
      information from medical multimedia data such as images, video and text, to
      populate our PHR timeline, while also embedding spatial and textual annotations
      such as regions of interest (ROIs) that are automatically derived from image
      processing algorithms. We developed a prototype to process the various forms of
      PHR data and present the data in a graphical avatar. We analysed the usefulness
      of our system under various scenarios of patient data use and present preliminary
      results that indicate that our system performs well on standard consumer
      hardware. 

PMID- 24110655
TI  - Patient in control in clinical trials - European initiatives for improving
      patient empowerment in clinical trials through technical implementation of legal
      norms.
AB  - Patient empowerment is acclaimed as one of the major trends in the health care
      area bringing forward new conceptions how to involve patients in clinical
      research in a more (inter)active way. Patients and clinicians could benefit from
      more flexible consent-management and improved communication processes. This is
      where technology comes as an asset - the novel technological approaches promise
      to give more control to the patient, lessen the burdens on the researchers and
      all that in compliance with the legal and ethical requirements (e.g. data
      protection). The views of the European projects EURECA and p-medicine serve as
      examples for European approaches to patient empowerment. 

PMID- 24110656
TI  - Protection of electronic health records (EHRs) in cloud.
AB  - EHR technology has come into widespread use and has attracted attention in
      healthcare institutions as well as in research. Cloud services are used to build
      efficient EHR systems and obtain the greatest benefits of EHR implementation.
      Many issues relating to building an ideal EHR system in the cloud, especially the
      tradeoff between flexibility and security, have recently surfaced. The privacy of
      patient records in cloud platforms is still a point of contention. In this
      research, we are going to improve the management of access control by restricting
      participants' access through the use of distinct encrypted parameters for each
      participant in the cloud-based database. Also, we implement and improve an
      existing secure index search algorithm to enhance the efficiency of information
      control and flow through a cloud-based EHR system. At the final stage, we
      contribute to the design of reliable, flexible and secure access control,
      enabling quick access to EHR information. 

PMID- 24110658
TI  - Effect of temporal fine structure on speech intelligibility modeling.
AB  - Temporal fine structure (TFS) carries important information for the speech
      perception of hearing-impaired listeners and for the design of novel prosthetic
      hearing devices. This study assessed the performance of present intelligibility
      indices for predicting the intelligibility of speech containing different amount
      of TFS information. Speech intelligibility data was collected from vocoded and
      wideband Mandarin sentences containing little/partial and intact TFS information,
      respectively, and was then subjected to the correlation analysis with existing
      intelligibility indices. It was found that, though performing well in predicting
      the intelligibility of vocoded or wideband speech separately, present
      intelligibility indices were not highly correlated with the intelligibility
      scores when a general function was used to map all intelligibility measures to
      intelligibility scores. Analysis further showed that the intelligibility
      prediction power could be significantly improved when multiple condition
      dependent functions were used for mapping intelligibility measures to
      intelligibility scores. 

PMID- 24110659
TI  - Clustering of atrial fibrillation based on surface ECG measurements.
AB  - Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical
      research. In particular, the study of AF types or sub-classes is a very
      interesting research topic. In this paper we present a preliminary study to find
      sub-classes of AF from real 12-lead ECG recordings using k-means and hierarchical
      clustering algorithms. We applied blind source separation to an initial set of
      218 recordings from which we extracted a subset of 136 atrial activity signals
      displaying known properties of AF. As features for clustering we proposed the
      peak frequency mean value (PFM), peak frequency standard deviation (PFSD) and the
      spectral concentration (SC). We computed the silhouette coefficient to obtain an
      optimal number of clusters of k=5, and conducted preliminary feature selection to
      evaluate clustering quality. We observed that the separability increases if we
      discard SC as a feature. The proposed method is the first stage to a future AF
      classification method, which combined with specialist advice, should help in the
      clinical field. 

PMID- 24110661
TI  - Impact of bipolar electrodes contact on fractionation index measurement.
AB  - Signals such as Complex Fractionated Atrial Electrograms (CFAE) are tracked
      during ablation procedures to locate the arrhythmical substrate regions. Most of
      CFAE classification tools use fractionation indexes. However, recordings from
      intracardiac catheter depend on electrode contact quality. This paper
      investigates the impact of electrode contact area on fractionation indexes. It is
      assessed through three kinds of arrhythmical activations resulting from a
      numerical simulation of a small piece of the cardiac tissue. Bipolar electrograms
      are extracted corresponding to 25 different contact areas and fractionation
      indexes (Shannon entropy, non linear energy operator and maximum peak ratio) are
      computed. Results yield that the Shannon entropy offers a good potential
      discrimination between arrhythmic scenarios and is less sensitive to the
      electrode contact variation. 

PMID- 24110660
TI  - Single-trial laser-evoked potentials feature extraction for prediction of pain
      perception.
AB  - Pain is a highly subjective experience, and the availability of an objective
      assessment of pain perception would be of great importance for both basic and
      clinical applications. The objective of the present study is to develop a novel
      approach to extract pain-related features from single-trial laser-evoked
      potentials (LEPs) for classification of pain perception. The single-trial LEP
      feature extraction approach combines a spatial filtering using common spatial
      pattern (CSP) and a multiple linear regression (MLR). The CSP method is effective
      in separating laser-evoked EEG response from ongoing EEG activity, while MLR is
      capable of automatically estimating the amplitudes and latencies of N2 and P2
      from single-trial LEP waveforms. The extracted single-trial LEP features are used
      in a Naive Bayes classifier to classify different levels of pain perceived by the
      subjects. The experimental results show that the proposed single-trial LEP
      feature extraction approach can effectively extract pain-related LEP features for
      achieving high classification accuracy. 

PMID- 24110662
TI  - Improving activity recognition using temporal coherence.
AB  - Assessment of daily physical activity using data from wearable sensors has
      recently become a prominent research area in the biomedical engineering field and
      a substantial application for pattern recognition. In this paper, we present an
      accelerometer-based activity recognition scheme on the basis of a hierarchical
      structured classifier. A first step consists of distinguishing static activities
      from dynamic ones in order to extract relevant features for each activity type.
      Next, a separate classifier is applied to detect more specific activities of the
      same type. On top of our activity recognition system, we introduce a novel
      approach to take into account the temporal coherence of activities. Inter
      activity transition information is modeled by a directed graph Markov chain.
      Confidence measures in activity classes are then evaluated from conventional
      classifier's outputs and coupled with the graph to reinforce activity estimation.
      Accurate results and significant improvement of activity detection are obtained
      when applying our system for the recognition of 9 activities for 48 subjects. 

PMID- 24110663
TI  - Automatic classification of time-frequency plots applied to the center-of
      pressure rotational components.
AB  - Time-frequency plots are widely applied to the non-stationary analysis of
      signals. These plots may be difficult to interpret, particularly when large data
      sets have to be considered. The aim of this work is to propose an automatic
      procedure of feature selection and clustering to be applied to time-frequency
      plots. We focus on the application of this procedure to plots obtained from a non
      stationary analysis of the center-of-pressure signals acquired in upright bipedal
      stance. From a data set of 168 time-frequency plots we obtained 5 different
      clusters, each characterized by a few distinctive features. We were able to
      interpret the results of the clustering relating them to the physiological
      mechanisms underlying postural sway. 

PMID- 24110664
TI  - Comparison of surface and intramuscular EMG pattern recognition for simultaneous
      wrist/hand motion classification.
AB  - The simultaneous control of multiple degrees of freedom (DOFs) is important for
      the intuitive, life-like control of artificial limbs. The objective of this study
      was to determine whether the use of intramuscular electromyogram (EMG) improved
      pattern classification of simultaneous wrist/hand movements compared to surface
      EMG. Two pattern classification methods were used in this analysis, and were
      trained to predict 1-DOF and 2-DOF movements involving wrist rotation, wrist
      flexion/extension, and hand open/close. The classification methods used were (1)
      a single pattern classifier discriminating between 1-DOF and 2-DOF motion
      classes, and (2) a parallel set of three classifiers to predict the activity of
      each of the 3 DOFs. We demonstrate that in this combined wrist/hand
      classification task, the use of intramuscular EMG significantly decreases
      classification error compared to surface EMG for the parallel configuration
      (p<0.01), but not for the single classifier. We also show that the use of
      intramuscular EMG mitigates the increase in errors produced when the parallel
      classifier method is trained without 2-DOF motion class data. 

PMID- 24110665
TI  - Combined use of sEMG and accelerometer in hand motion classification considering
      forearm rotation.
AB  - Hand motion classification using surface electromyography (sEMG) has been widely
      studied for its applications in upper-limb prosthesis and human-machine interface
      etc. Pattern-recognition based control methods have many advantages, and the
      reported classification accuracy can meet the requirements of practical
      applications. However, the pattern instability of sEMG in actual use limited
      their real implementations, and limb position variations may be one of the
      potential factors. In this paper, we give a pilot study of the reverse effect of
      forearm rotations on hand motion classification, and the results show that the
      forearm rotations can substantially degrade the classifier's performance: the
      average intra-position error is only 2.4%, but the average interposition
      classification error is as high as 44.0%. To solve this problem, we use an extra
      accelerometer to estimate the forearm rotation angles, and the best combination
      of sEMG data and accelerometer outputs can reduce the average classification
      error to 3.3%.

PMID- 24110666
TI  - Ensemble regularized linear discriminant analysis classifier for P300-based brain
      computer interface.
AB  - This paper demonstrates a better classification performance of an ensemble
      classifier using a regularized linear discriminant analysis (LDA) for P300-based
      brain-computer interface (BCI). The ensemble classifier with an LDA is sensitive
      to the lack of training data because covariance matrices are estimated
      imprecisely. One of the solution against the lack of training data is to employ a
      regularized LDA. Thus we employed the regularized LDA for the ensemble classifier
      of the P300-based BCI. The principal component analysis (PCA) was used for the
      dimension reduction. As a result, an ensemble regularized LDA classifier showed
      significantly better classification performance than an ensemble un-regularized
      LDA classifier. Therefore the proposed ensemble regularized LDA classifier is
      robust against the lack of training data. 

PMID- 24110667
TI  - EEG classification of physiological conditions in 2D/3D environments using neural
      network.
AB  - Higher classification accuracy is more desirable for brain computer interface
      (BCI) applications. The accuracy can be achieved by appropriate selection of
      relevant features. In this paper a new scheme is proposed based on six different
      nonlinear features. These features include Sample entropy (SampEn), Composite
      permutation entropy index (CPEI), Approximate entropy (ApEn), Fractal dimension
      (FD), Hurst exponent (H) and Hjorth parameters (complexity and mobility). These
      features are decision variables for classification of physiological conditions:
      Eyes Open (EO), Eyes Closed (EC), Game Playing 2D (GP2D), Game playing 3D active
      (GP3DA) and Game playing 3D passive (GP3DP). Results show that the scheme can
      successfully classify the conditions with an accuracy of 88.9%. 

PMID- 24110668
TI  - Noise enhanced array signal detection in P300 speller paradigm using ICA-based
      subspace projections.
AB  - This paper explores how noise can improve prediction accuracy of the Event
      Related Potential (ERP) based on P300 signals. We propose an array of ICA-Based
      P300 processing systems with additive white Gaussian noise. The array system
      attains maximum accuracy when noise intensity is not zero and thus the system
      shows the stochastic resonance effect. The prediction accuracy increases as the
      number of stages of the array increases. Experimental results show that
      increasing the array size with the proper amount of noise can improve the
      accuracy of the original P300 signal detection using ICA-based subspace
      projection technique. 

PMID- 24110669
TI  - Automatic estimation of sleep level for nap based on conditional probability of
      sleep stages and an exponential smoothing method.
AB  - An automatic sleep level estimation method was developed for monitoring and
      regulation of day time nap sleep. The recorded nap data is separated into
      continuous 5-second segments. Features are extracted from EEGs, EOGs and EMG. A
      parameter of sleep level is defined which is estimated based on the conditional
      probability of sleep stages. An exponential smoothing method is applied for the
      estimated sleep level. There were totally 12 healthy subjects, with an averaged
      age of 22 yeas old, participated into the experimental work. Comparing with sleep
      stage determination, the presented sleep level estimation method showed better
      performance for nap sleep interpretation. Real time monitoring and regulation of
      nap is realizable based on the developed technique. 

PMID- 24110670
TI  - Accurate arrhythmia classification using auto-associative neural network.
AB  - Currently about one in eighteen of the American population suffer from cardiac
      Arrhythmias that lead to Coronary Heart Diseases and this rate is steadily
      increasing. An early monitoring and diagnosis of Arrhythmia based on
      Electrocardiogram signals can help in reducing mortality. This paper primarily
      focuses on the application of Auto Associative Neural Network as a new
      classification approach, which does not require feature extraction task. The
      weights of a trained Neural Network are stored as class representative models
      that results in high compression gain with respect to the size of training data.
      The evaluation of the proposed technique is tested on segmented ECG beats of four
      different classes of Arrhythmia excluding normal pattern. These beats have been
      extracted from the MIT/BIH Arrhythmia database and compared against the state-of
      the art template matching technique such as Dynamic Time Warping. The proposed
      technique yields an average accuracy of more than 97% and a relative compression
      gain of above 90%. 

PMID- 24110671
TI  - Asynchronous brain-computer interfacing based on intended movement direction.
AB  - A brain-computer interface (BCI) is a technique for controlling devices with the
      measured human brain activities. Especially, an asynchronous BCI is one of the
      most important topics since practical input interfaces are incomplete without
      self-paced inputs. In order to construct an asynchronous BCI, it is essential to
      recognize the standby state, where a user enters no commands. In this paper, we
      propose a novel method for detecting the standby state and develop an
      asynchronous BCI based on event-related potentials with the intended movement
      direction.We conducted online experiments with developed asynchronous BCI. As a
      result, all three subjects showed considerable recognition accuracies. 

PMID- 24110672
TI  - Effectiveness of different sensing modalities in predicting targets of reaching
      movements.
AB  - Human motion recognition is essential for many biomedical applications, but few
      studies compare the abilities of multiple sensing modalities. This paper thus
      evaluates the effectiveness of different modalities when predicting targets of
      human reaching movements. Electroencephalography, electrooculography, camera
      based eye tracking, electromyography, hand tracking and the user's preferences
      are used to make predictions at different points in time. Prediction accuracies
      are calculated based on data from 10 subjects in within-subject crossvalidation.
      Results show that electroencephalography can make predictions before limb motion
      onset, but its accuracy decreases as the number of potential targets increases.
      Electromyography and hand tracking give high accuracy, but only after motion
      onset. Eye tracking is robust and gives high accuracy at limb motion onset.
      Combining multiple modalities can increase accuracy, though not always. While
      many studies have evaluated individual sensing modalities, this study provides
      quantitative data on many modalities at different points of time in a single
      setting. The information could help biomedical engineers choose the most
      appropriate equipment for a particular application. 

PMID- 24110673
TI  - A novel biometric authentication approach using electrocardiogram signals.
AB  - In this work, we present a novel biometric authentication approach based on
      combination of AC/DCT features, MFCC features, and QRS beat information of the
      ECG signals. The proposed approach is tested on a subset of 30 subjects selected
      from the PTB database. This subset consists of 13 healthy and 17 non-healthy
      subjects who have two ECG records. The proposed biometric authentication approach
      achieves average frame recognition rate of %97.31 on the selected subset. Our
      experimental results imply that the frame recognition rate of the proposed
      authentication approach is better than that of ACDCT and MFCC based biometric
      authentication systems, individually. 

PMID- 24110674
TI  - Using EEG spatial correlation, cross frequency energy, and wavelet coefficients
      for the prediction of Freezing of Gait in Parkinson's Disease patients.
AB  - Parkinson's Disease (PD) patients with Freezing of Gait (FOG) often experience
      sudden and unpredictable failure in their ability to start or continue walking,
      making it potentially a dangerous symptom. Emerging knowledge about brain
      connectivity is leading to new insights into the pathophysiology of FOG and has
      suggested that electroencephalogram (EEG) may offer a novel technique for
      understanding and predicting FOG. In this study we have integrated spatial,
      spectral, and temporal features of the EEG signals utilizing wavelet coefficients
      as our input for the Multilayer Perceptron Neural Network and k-Nearest Neighbor
      classifier. This approach allowed us to predict transition from walking to
      freezing with 87 % sensitivity and 73 % accuracy. This preliminary data affirms
      the functional breakdown between areas in the brain during FOG and suggests that
      EEG offers potential as a therapeutic strategy in advanced PD. 

PMID- 24110675
TI  - An adaptation strategy of using LDA classifier for EMG pattern recognition.
AB  - The time-varying character of myoelectric signal usually causes a low
      classification accuracy in traditional supervised pattern recognition method. In
      this work, an unsupervised adaptation strategy of linear discriminant analysis
      (ALDA) based on probability weighting and cycle substitution was suggested in
      order to improve the performance of electromyography (EMG)-based motion
      classification in multifunctional myoelectric prostheses control in changing
      environment. The adaptation procedure was firstly introduced, and then the
      proposed ALDA classifier was trained and tested with surface EMG recordings
      related to multiple motion patterns. The accuracies of the ALDA classifier and
      traditional LDA classifier were compared when the EMG recordings were added with
      different degrees of noise. The experimental results showed that compared to the
      LDA method, the suggested ALDA method had a better performance in improving the
      classification accuracy of sEMG pattern recognition, in both stable situation and
      noise added situation. 

PMID- 24110676
TI  - Automated assessment of mobility in bedridden patients.
AB  - Immobility in older patients is a costly problem for both patients and healthcare
      workers. The Hierarchical Assessment of Balance and Mobility (HABAM) is a
      clinical tool able to assess immobile patients and predict morbidity, yet could
      become more reliable and informative through automation. This paper proposes an
      algorithm to automatically determine which of three enacted HABAM scores
      (associated with bedridden patients) had been performed by volunteers. A laptop
      was used to gather pressure data from three mats placed on a standard hospital
      bed frame while five volunteers performed three enactments each. A system of
      algorithms was created, consisting of three subsystems. The first subsystem used
      mattress data to calculate individual sensor sums and eliminate the weight of the
      mattress. The second subsystem established a baseline pressure reading for each
      volunteer and used percentage change to identify and distinguish between two
      enactments. The third subsystem used calculated weight distribution ratios to
      determine if the data represented the remaining enactment. The system was tested
      for accuracy by inputting the volunteer data and recording the assessment output
      (a score per data set). The system identified 13 of 15 sets of volunteer data as
      expected. Examination of these results indicated that the two sets of data were
      not misidentified; rather, the volunteers had made mistakes in performance. These
      results suggest that this system of algorithms is effective in distinguishing
      between the three HABAM score enactments examined here, and emphasizes the
      potential for pervasive computing to improve traditional healthcare. 

PMID- 24110677
TI  - Classification of iRBD and Parkinson's patients using a general data-driven sleep
      staging model built on EEG.
AB  - Sleep analysis is an important diagnostic tool for sleep disorders. However, the
      current manual sleep scoring is time-consuming as it is a crude discretization in
      time and stages. This study changes Esbroeck and Westover's [1] latent sleep
      staging model into a global model. The proposed data-driven method trained a
      topic mixture model on 10 control subjects and was applied on 10 other control
      subjects, 10 iRBD patients and 10 Parkinson's patients. In that way 30 topic
      mixture diagrams were obtained from which features reflecting distinct sleep
      architectures between control subjects and patients were extracted. Two features
      calculated on basis of two latent sleep states classified subjects as "control"
      or "patient" by a simple clustering algorithm. The mean sleep staging accuracy
      compared to classical AASM scoring was 72.4% for control subjects and a
      clustering of the derived features resulted in a sensitivity of 95% and a
      specificity of 80 %. This study demonstrates that frequency analysis of sleep EEG
      can be used for data-driven global sleep classification and that topic features
      separates iRBD and Parkinson's patients from control subjects. 

PMID- 24110678
TI  - Semi-supervised adaptation in ssvep-based brain-computer interface using tri
      training.
AB  - This paper presents a novel and computationally simple tri-training based semi
      supervised steady-state visual evoked potential (SSVEP)-based brain-computer
      interface (BCI). It is implemented with autocorrelation-based features and a
      Naive-Bayes classifier (NBC). The system uses nine characters presented on a 100
      Hz CRT-monitor, three scalp electrodes for signal acquisition, a gUSB-amp for
      preamplification and two PCs for data-processing and stimulus control
      respectively. Preliminary test results of the system on nine healthy subjects,
      with and without tri-training, indicates that the accuracy improves as a result
      of tri-training. 

PMID- 24110679
TI  - Automatic characterization of dynamics in Absence Epilepsy.
AB  - Dynamics of the spike-wave paroxysms in Childhood Absence Epilepsy (CAE) are
      automatically characterized using novel approaches. Features are extracted from
      scalograms formed by Continuous Wavelet Transform (CWT). Detection algorithms are
      designed to identify an estimate of the temporal development of frequencies in
      the paroxysms. A database of 106 paroxysms from 26 patients was analyzed. The
      database is large compared to other known studies in the field of dynamics in
      CAE. CWT is more efficient than the widely used Fourier transform due to CWTs
      ability to recognize smaller discontinuities and variations. The use of
      scalograms and the detection algorithms result in a potentially usable clinical
      tool for dividing CAE patients into subsets. Differences between the grouped
      paroxysms may turn out to be useful from a clinical perspective as a prognostic
      indicator or when adjusting drug treatment. 

PMID- 24110680
TI  - EEG-based recognition of video-induced emotions: selecting subject-independent
      feature set.
AB  - Emotions are fundamental for everyday life affecting our communication, learning,
      perception, and decision making. Including emotions into the human-computer
      interaction (HCI) could be seen as a significant step forward offering a great
      potential for developing advanced future technologies. While the electrical
      activity of the brain is affected by emotions, offers electroencephalogram (EEG)
      an interesting channel to improve the HCI. In this paper, the selection of
      subject-independent feature set for EEG-based emotion recognition is studied. We
      investigate the effect of different feature sets in classifying person's arousal
      and valence while watching videos with emotional content. The classification
      performance is optimized by applying a sequential forward floating search
      algorithm for feature selection. The best classification rate (65.1% for arousal
      and 63.0% for valence) is obtained with a feature set containing power spectral
      features from the frequency band of 1-32 Hz. The proposed approach substantially
      improves the classification rate reported in the literature. In future, further
      analysis of the video-induced EEG changes including the topographical differences
      in the spectral features is needed. 

PMID- 24110681
TI  - Classifying the speech response of the brain using Gaussian hidden markov model
      (HMM) with independent component analysis (ICA).
AB  - The purpose of this paper is to determine whether electroencephalograpy (EEG) can
      be used as a tool for hearing impairment tests such as hearing screening. For
      this study, we recorded EEG responses to two syllables, /a/ and /u/, in Korean
      from three subjects at Gwangju Institute of Science and Technology. The ultimate
      goal of this study is to classify speech sound data regardless of their size
      using EEG; however, as an initial stage of the study, we classified only two
      different speech syllables using Gaussian hidden markov model. The result of this
      study shows a possibility that EEG could be used for hearing screening and other
      diagnostic tools related to speech perception. 

PMID- 24110682
TI  - Exploratory study of EEG burst characteristics in preterm infants.
AB  - In this paper, we study machine learning techniques and features of
      electroencephalography activity bursts for predicting outcome in extremely
      preterm infants. It was previously shown that the distribution of interburst
      interval durations predicts clinical outcome, but in previous work the
      information within the bursts has been neglected. In this paper, we perform
      exploratory analysis of feature extraction of burst characteristics and use
      machine learning techniques to show that such features could be used for outcome
      prediction. The results are promising, but further verification in larger
      datasets is needed to obtain conclusive results. 

PMID- 24110683
TI  - Event-related evoked potentials in Alzheimer's disease by a tool-using gesture
      paradigm.
AB  - The Alzheimer's disease (AD) has a wide spectrum of symptoms, ranging from
      cognition dysfunction to behavior disturbances and functional impairment. The
      evoked cerebral potentials by specific paradigms are useful for disclosing
      neuropsychological activities. The evolution of AD is accompanied by progressive
      cognitive impairment which may result in a difficulty to recognize or comprehend
      gestures. In the present study, a visual tool-using gesture paradigm was employed
      to assess the cognitive functions of 16 probable AD patients, 17 subjects mild
      cognitive impairment (MCI), and 17 age-matched control subjects. Each subject was
      conducted by visual stimuli by a series of pictures, each displaying randomly a
      gesture with correctly or incorrectly using a tool. The P300 amplitude was
      further used as a parameter to build classifiers based on support vector machine.

PMID- 24110684
TI  - A self produced mother wavelet feature extraction method for motor imagery brain
      computer interface.
AB  - Motor imagery base brain-computer interface (BCI) is an appropriate solution for
      stroke patient to rehabilitate and communicate with external world. For such
      applications speculating whether the subjects are doing motor imagery is our
      primary mission. So the problem turns into how to precisely classify the two
      tasks, motor imagery and idle state, by using the subjects'
      electroencephalographic (EEG) signals. Feature extraction is a factor that
      significantly affects the classification result. Based on the concept of
      Continuous Wavelet Transform, we proposed a wavelet-liked feature extraction
      method for motor imagery discrimination. And to compensate the problem that the
      feature varies between subjects, we use the subjects' own EEG signals as the
      mother wavelet. After determining the feature vector, we choose Bayes linear
      discriminant analysis (LDA) as our classifier. The BCI competition III dataset
      IVa is used to evaluate the classification performance. Comparing with variance
      and fast Fourier transform (FFT) methods in feature extraction, 2.02% and 16.96%
      improvement in classification accuracy are obtained in this work respectively. 

PMID- 24110685
TI  - Single-trial EEG-based emotion recognition using kernel Eigen-emotion pattern and
      adaptive support vector machine.
AB  - Single-trial electroencephalography (EEG)-based emotion recognition enables us to
      perform fast and direct assessments of human emotional states. However, previous
      works suggest that a great improvement on the classification accuracy of valence
      and arousal levels is still needed. To address this, we propose a novel emotional
      EEG feature extraction method: kernel Eigen-emotion pattern (KEEP). An adaptive
      SVM is also proposed to deal with the problem of learning from imbalanced
      emotional EEG data sets. In this study, a set of pictures from IAPS are used for
      emotion induction. Results based on seven participants show that KEEP gives much
      better classification results than the widely-used EEG frequency band power
      features. Also, the adaptive SVM greatly improves classification performance of
      commonly-adopted SVM classifier. Combined use of KEEP and adaptive SVM can
      achieve high average valence and arousal classification rates of 73.42% and
      73.57%. The highest classification rates for valence and arousal are 80% and 79%,
      respectively. The results are very promising. 

PMID- 24110686
TI  - Mu rhythm suppression during the imagination of observed action.
AB  - Mu wave suppression is thought to accompany the activation of the mirror neuron
      system which occurs when a human observes or imitates the behavior of others. Our
      investigation indicates a possible difference in mirror neuron system activation
      between passive and more active observation as suggested by mu wave activation
      levels. Participants were asked to observe four different videos each 80 s in
      duration. Each video was repeated once after a 30 s interval. The first video was
      of visual white noise and participants were instructed to passively observe the
      video. This was identified as the Baseline condition and served as a mu
      activation level baseline. The second video was of simple bouncing balls and the
      observer was again asked to passively observe the video (Ball condition). The
      third video was of a moving hand (Observation condition). The forth video was of
      the same moving hand and participants also imagined executing the observed hand
      movement (Imagination condition). As hypothesized, the Imagination condition
      activated the greatest level of mu suppression, while the Ball condition
      activated the lowest level of mu wave suppression. The Observation condition
      produced a slightly larger level of mu wave suppression than the Ball condition.
      This progressive increase in mu wave suppression supports the hypothesis that the
      activation of the mirror neuron system increases as the level of active
      observation increases. 

PMID- 24110687
TI  - EEG seizure detection and epilepsy diagnosis using a novel variation of Empirical
      Mode Decomposition.
AB  - Epileptic seizure detection and epilepsy diagnosis based on feature extraction
      and classification using electroencephalography (EEG) signals is an important
      area of research. In this paper, we present a simple and effective approach based
      on signal decomposition, using a novel variation of the Empirical Mode
      Decomposition called Empirical Mode Decomposition-Modified Peak Selection (EMD
      MPS). EMD-MPS allows time-scale based de-trending of signals, allowing signals to
      be separated directly into a de-trended component, and a trend, according to a
      frequency separation criterion. Features are extracted from the decomposed
      components, and a simple classifier, namely the 1-NN classifier is used for three
      classification tasks. The technique is tested on a publicly available EEG
      database, and a classification accuracy of 99% for epilepsy diagnosis task, and
      100% and 98.2% for two seizure detection tasks is obtained. These results are
      better than, or comparable to previous results using the same EEG database, but
      have been obtained with a simpler and computationally fast signal analysis and
      classification method. 

PMID- 24110688
TI  - Non-negative matrix factorization and sparse representation for sleep signal
      classification.
AB  - Real-life signals such as biomedical signals are non-stationary and random in
      their pattern, and cannot be characterized by any specific waveform or spectral
      content. Processing of these natural signals involves consideration of certain
      significant attributes such as their non-stationary behavior over time, scaling
      behavior, translation invariance. Due to their random behavior, the existing
      discriminative methods often fail to provide a reasonable quantification
      performance, thereby resulting in poor classification rates. In order to address
      this issue, there exists a need for defining a suitable theoretical framework for
      biomedical signals. We have proposed, a robust Time-Frequency Nonnegative Matrix
      Factorization (TF-NMF) framework that uses sparse representation for
      quantification of sleep signals. This scheme incorporates a novel feature
      extraction algorithm. For signals that are nonstationary in nature, the degree of
      sparsity is lower compared to the stationary signals. This results into poor
      classification accuracy. However our proposed approach has proven that using NMF
      as input to the sparse representation for classification will improve the
      discrimination performance. Overall, maximum cross-validation performance of
      87:9% was obtained, using the leave-one-out (LOO) approach for sleep abnormality
      detection using EMG signals. Although the computational complexity of the
      proposed algorithm might be higher compared to the other similar methods, this TF
      NMF based method shows great potential for quantification and localization of
      time varying signals. 

PMID- 24110689
TI  - Dynamic physiological signal analysis based on Fisher kernels for emotion
      recognition.
AB  - Emotional behavior is an active area of study in the fields of neuroscience and
      affective computing. This field has the fundamental role of emotion recognition
      in the maintenance of physical and mental health. Valence/Arousal levels are two
      orthogonal, independent dimensions of any emotional stimulus and allows an
      analysis framework in affective research. In this paper we present our framework
      for emotional regression based on machine learning techniques. Autoregressive
      coefficients and hidden markov models on physiological signals, based on Fisher
      Kernels characterization are presented for mapping variable length sequences to
      new dimension feature vector space. Then, support vector regression is performed
      over the Fisher Scores for emotional recognition. Also quantitatively we
      evaluated the accuracy of the proposed model by acomplishing a hold-out cross
      validation over the dataset. The experimental results show that the proposed
      model can effectively perform the regression in comparison with static
      characterization methods. 

PMID- 24110690
TI  - Unsupervised learning applied in MER and ECG signals through Gaussians mixtures
      with the Expectation-Maximization algorithm and Variational Bayesian Inference.
AB  - Automatic identification of biosignals is one of the more studied fields in
      biomedical engineering. In this paper, we present an approach for the
      unsupervised recognition of biomedical signals: Microelectrode Recordings (MER)
      and Electrocardiography signals (ECG). The unsupervised learning is based in
      classic and bayesian estimation theory. We employ gaussian mixtures models with
      two estimation methods. The first is derived from the frequentist estimation
      theory, known as Expectation-Maximization (EM) algorithm. The second is obtained
      from bayesian probabilistic estimation and it is called variational inference. In
      this framework, both methods are used for parameters estimation of Gaussian
      mixtures. The mixtures models are used for unsupervised pattern classification,
      through the responsibility matrix. The algorithms are applied in two real
      databases acquired in Parkinson's disease surgeries and electrocardiograms. The
      results show an accuracy over 85% in MER and 90% in ECG for identification of two
      classes. These results are statistically equal or even better than parametric
      (Naive Bayes) and nonparametric classifiers (K-nearest neighbor). 

PMID- 24110691
TI  - Feature selection for multimodal emotion recognition in the arousal-valence
      space.
AB  - Emotion recognition is a challenging research problem with a significant
      scientific interest. Most of the emotion assessment studies have focused on the
      analysis of facial expressions. Recently, it has been shown that the simultaneous
      use of several biosignals taken from the patient may improve the classification
      accuracy. An open problem in this area is to identify which biosignals are more
      relevant for emotion recognition. In this paper, we perform Recursive Feature
      Elimination (RFE) to select a subset of features that allows emotion
      classification. Experiments are carried out over a multimodal database with
      arousal and valence annotations, and a diverse range of features extracted from
      physiological, neurophysiological, and video signals. Results show that several
      features can be eliminated while still preserving classification accuracy in
      setups of 2 and 3 classes. Using a small subset of the features, it is possible
      to reach 70% accuracy for arousal and 60% accuracy for valence in some
      experiments. Experimentally, it is shown that the Galvanic Skin Response (GSR) is
      relevant for arousal classification, while the electroencephalogram (EEG) is
      relevant for valence. 

PMID- 24110692
TI  - Analysis of adventitious lung sounds originating from pulmonary tuberculosis.
AB  - Tuberculosis is a common and potentially deadly infectious disease, usually
      affecting the respiratory system and causing the sound properties of symptomatic
      infected lungs to differ from non-infected lungs. Auscultation is often ruled out
      as a reliable diagnostic technique for TB due to the random distribution of the
      infection and the varying severity of damage to the lungs. However, advancements
      in signal processing techniques for respiratory sounds can improve the potential
      of auscultation far beyond the capabilities of the conventional mechanical
      stethoscope. Though computer-based signal analysis of respiratory sounds has
      produced a significant body of research, there have not been any recent
      investigations into the computer-aided analysis of lung sounds associated with
      pulmonary Tuberculosis (TB), despite the severity of the disease in many
      countries. In this paper, respiratory sounds were recorded from 14 locations
      around the posterior and anterior chest walls of healthy volunteers and patients
      infected with pulmonary TB. The most significant signal features in both the time
      and frequency domains associated with the presence of TB, were identified by
      using the statistical overlap factor (SOF). These features were then employed to
      train a neural network to automatically classify the auscultation recordings into
      their respective healthy or TB-origin categories. The neural network yielded a
      diagnostic accuracy of 73%, but it is believed that automated filtering of the
      noise in the clinics, more training samples and perhaps other signal processing
      methods can improve the results of future studies. This work demonstrates the
      potential of computer-aided auscultation as an aid for the diagnosis and
      treatment of TB. 

PMID- 24110693
TI  - Tremor modulations across periods with and without voluntary motion and limb load
      task demands using movement quantification.
AB  - Understanding the neurobiological mechanisms underlying different types of tremor
      and the altered functional connectivity of the involved areas is a timely goal in
      clinical neuroscience. If successful, this quest may open new perspectives on how
      to achieve tremor modulation, which is notably relevant, in Parkinson's disease
      (PD). Tremor can be characterized by simple parameters such as frequency and
      amplitude. It is therefore prone to be objectively targeted by neuromodulation
      and quantitatively investigated using multimodal techniques, such as,
      accelerometry, EMG and functional Magnetic Resonance Imaging (fMRI). Embarking on
      the latter challenge requires an a priori knowledge of how effective functional
      connectivity is altered in PD tremor. This works aims to ascertain which postural
      and voluntary movement tasks with distinct types of physical load are suitable
      for designing efficient fMRI protocols, by performing an accelerometry analysis
      to measure spontaneous and imposed tremor modulation on cohorts of PD patients,
      essential tremor patients and a group of voluntary healthy controls. 

PMID- 24110694
TI  - Exploring neural directed interactions with transfer entropy based on an adaptive
      kernel density estimator.
AB  - This paper aims at estimating causal relationships between signals to detect flow
      propagation in autoregressive and physiological models. The main challenge of the
      ongoing work is to discover whether neural activity in a given structure of the
      brain influences activity in another area during epileptic seizures. This
      question refers to the concept of effective connectivity in neuroscience, i.e. to
      the identification of information flows and oriented propagation graphs. Past
      efforts to determine effective connectivity rooted to Wiener causality definition
      adapted in a practical form by Granger with autoregressive models. A number of
      studies argue against such a linear approach when nonlinear dynamics are
      suspected in the relationship between signals. Consequently, nonlinear
      nonparametric approaches, such as transfer entropy (TE), have been introduced to
      overcome linear methods limitations and promoted in many studies dealing with
      electrophysiological signals. Until now, even though many TE estimators have been
      developed, further improvement can be expected. In this paper, we investigate a
      new strategy by introducing an adaptive kernel density estimator to improve TE
      estimation. 

PMID- 24110695
TI  - The effect of normalization of Partial Directed Coherence on the statistical
      assessment of connectivity patterns: a simulation study.
AB  - Partial Directed Coherence (PDC) is a spectral multivariate estimator for
      effective connectivity, relying on the concept of Granger causality. Even if its
      original definition derived directly from information theory, two modifies were
      introduced in order to provide better physiological interpretations of the
      estimated networks: i) normalization of the estimator according to rows, ii)
      squared transformation. In the present paper we investigated the effect of PDC
      normalization on the performances achieved by applying the statistical validation
      process on investigated connectivity patterns under different conditions of
      Signal to Noise ratio (SNR) and amount of data available for the analysis.
      Results of the statistical analysis revealed an effect of PDC normalization only
      on the percentages of type I and type II errors occurred by using Shuffling
      procedure for the assessment of connectivity patterns. No effects of the PDC
      formulation resulted on the performances achieved during the validation process
      executed instead by means of Asymptotic Statistic approach. Moreover, the
      percentages of both false positives and false negatives committed by Asymptotic
      Statistic are always lower than those achieved by Shuffling procedure for each
      type of normalization. 

PMID- 24110696
TI  - Aged-related changes in brain activity classification with respect to age by
      means of graph indexes.
AB  - Recent studies have investigated changes in the human brain network organization
      during the normal aging. A reduction of the connectivity between brain areas was
      demonstrated by combining neuroimaging technologies and graph theory. Clustering,
      characteristic path length and small-worldness are key topological measures and
      they are widely used in literature. In this paper we propose a new methodology
      that combine advanced techniques of effective connectivity estimation, graph
      theoretical approach and classification by SVM method. EEG signals recording
      during rest condition from 20 young subjects and 20 mid-aged adults were studied.
      Partial Directed Coherence was computed by means of General Linear Kalman Filter
      and graph indexes were extracted from estimated patterns. At last small-worldness
      was used as feature for the SVM classifier. Results show that topological
      differences of brain networks exist between young and mid-aged adults: small
      worldness is significantly different between the two populations and it can be
      used to classify the subjects with respect to age with an accuracy of 69%. 

PMID- 24110697
TI  - Hidden Markov chain modeling for epileptic networks identification.
AB  - The partial epileptic seizures are often considered to be caused by a wrong
      balance between inhibitory and excitatory interneuron connections within a focal
      brain area. These abnormal balances are likely to result in loss of functional
      connectivities between remote brain structures, while functional connectivities
      within the incriminated zone are enhanced. The identification of the epileptic
      networks underlying these hypersynchronies are expected to contribute to a better
      understanding of the brain mechanisms responsible for the development of the
      seizures. In this objective, threshold strategies are commonly applied, based on
      synchrony measurements computed from recordings of the electrophysiologic brain
      activity. However, such methods are reported to be prone to errors and false
      alarms. In this paper, we propose a hidden Markov chain modeling of the synchrony
      states with the aim to develop a reliable machine learning methods for epileptic
      network inference. The method is applied on a real Stereo-EEG recording,
      demonstrating consistent results with the clinical evaluations and with the
      current knowledge on temporal lobe epilepsy. 

PMID- 24110698
TI  - Analysis of evoked deep brain connectivity.
AB  - Establishing dependencies and connectivity among different structures in the
      human brain is an extremely complex issue. Methods that are often used for
      connectivity analysis are based on correlation mechanisms. Correlation methods
      can analyze changes in signal shape or instantaneous power level. Although recent
      studies imply that observation of results from both groups of methods together
      can disclose some of the basic functions and behavior of the human brain during
      mental activity and decision-making, there is no technique covering changes in
      the shape of signals along with changes in their power levels. We present a
      method using a time evaluation of the correlation along with a comparison of
      power levels in every available contact pair from intracranial electrodes placed
      in deep brain structures. Observing shape changes in signals after stimulation
      together with their power levels provides us with new information about signal
      character between different structures in the brain during task-related events -
      visual stimulation with motor response. The results for a subject with 95
      intracerebral contacts used in this paper demonstrate a clear methodology capable
      of spatially analyzing connectivity among deep brain structures.

PMID- 24110699
TI  - Analysis of epileptic EEG signals in children by symbolic dynamics.
AB  - Epilepsy is one of the most prevalent neurological disorders among children. The
      study of surface EEG signals in patients with epilepsy by techniques based on
      symbolic dynamics can provide new insights into the epileptogenic process and may
      have considerable utility in the diagnosis and treatment of epilepsy. The goal of
      this work was to find patterns from a methodology based on symbolic dynamics to
      characterize seizures on surface EEG in pediatric patients with intractable
      epilepsy. A total of 76 seizures were analyzed by their pre-ictal, ictal and post
      ictal phases. An analytic signal envelope algorithm was applied to each EEG
      segment and its performance was evaluated. Several variables were defined from
      the distribution of words constructed on the EEG transformed into symbols. The
      results showed strong evidences of detectable non-linear changes in the EEG
      dynamics from pre-ictal to ictal phase and from ictal to post-ictal phase, with
      an accuracy higher than 70%. 

PMID- 24110700
TI  - Nonlinear estimation of coupling and directionality between signals: application
      to uterine EMG propagation.
AB  - Understanding the direction and quantity of information flowing in a complex
      system is a fundamental task in signal processing. Several measures have been
      proposed to detect the quantity of synchronization and the directionality between
      time series and in physiological data. In this paper we use two methods that are
      widely used in synchronization and directionality analysis: Nonlinear correlation
      coefficient (h(2)) and the general synchronization (H). The performances of both
      methods were tested on four dimensional coupled synthetic nonlinear Rossler
      models. They were then applied to a single real labor contraction uterine EMG
      burst with the aim of using them to detect synchronization and to plot the map of
      direction of information flow between the whole signal channels. The results on
      synthetic signal show a slight superiority of H over h(2). The results obtained
      on a single contraction are encouraging for the future use of these tools for
      resolving the open question of the directionality of uterine contractions and may
      provide a way of finding their source loci. 

PMID- 24110701
TI  - Monitoring the fetal heart rate variations by means of time-variant multivariate
      analysis.
AB  - The analysis of the fetal heart rate (fHR) is important in detecting the fetal
      distress related with hypoxic episodes, noticed sometimes during the uterine
      activity, which can severely affect the fetus. Occasional synchrony between the
      fHR and the maternal heart rate (mHR) was reported and the mHR shows some
      variations during pregnancy and labor, especially when the contractions are very
      strong. The current study proposes a new strategy to investigate the relations
      between the fHR, the mHR and the uterine activity, by applying the time-variant
      Partial Directed Coherence (tvPDC). 

PMID- 24110702
TI  - An active method for tracking connectivity in temporally changing brain networks.
AB  - The inference of connectivity in brain networks has typically been performed
      using passive measurements of ongoing activity across recording sites. Passive
      measures of connectivity are harder to interpret, however, in terms of causality 
      how evoked activity in one region might induce activity in another. To obviate
      this issue, recent work has proposed the use of active stimulation in conjunction
      with network estimation. By actively stimulating the network, more accurate
      information can be gleaned regarding evoked connectivity. The assumption in these
      previous works, however, was that the underlying networks were static and do not
      change in time. Such an assumption may be limiting in situations of clinical
      relevance, where the introduction of a drug or of brain pathology, might change
      the underlying networks structure. Here, an extension of the evoked connectivity
      paradigm is introduced that enables tracking networks that change in time. 

PMID- 24110703
TI  - Intraoperative tracking of aortic valve plane.
AB  - The main objective of this work is to track the aortic valve plane in intra
      operative fluoroscopic images in order to optimize and secure Transcatheter
      Aortic Valve Implantation (TAVI) procedure. This paper is focused on the issue of
      aortic valve calcifications tracking in fluoroscopic images. We propose a new
      method based on the Tracking-Learning-Detection approach, applied to the aortic
      valve calcifications in order to determine the position of the aortic valve plane
      in intra-operative TAVI images. This main contribution concerns the improvement
      of object detection by updating the recursive tracker in which all features are
      tracked jointly. The approach has been evaluated on four patient databases,
      providing an absolute mean displacement error less than 10 pixels (~2mm). Its
      suitability for the TAVI procedure has been analyzed. 

PMID- 24110705
TI  - Analysis of 3D cardiac deformations with 3D SinMod.
AB  - In this paper, we propose a novel 3D sine wave modeling (3D SinMod) approach to
      automatic analysis of 3D cardiac deformations. An accelerated 3D complementary
      spatial modulation of magnetization (CSPAMM) tagging technique was used to
      modulate the myocardial tissue and to acquire 3D MR data sets of the whole-heart
      including three orthog- onal tags within three breath-holds. Each tag set is able
      to assess the motion along a direction perpendicular to the tag lines. With the
      application of CSPAMM, the effect of tag fading encountered in SPAMM tagging due
      to T1 relaxation is mitigated and tag deformations can be visualized for the
      entire cardiac cycle, including diastolic phases. In the proposed approach, the
      environment around each voxel in the 3D volume is modeled as a moving sine
      wavefront with local frequency and amplitude. The biggest advantage of the
      proposed technique is that the entire framework, from data acquisition to data
      analysis is in the 3D domain, which permits quantification of both the in-plane
      and through-plane motion components. The accuracy and the effectiveness of the
      proposed method has been validated using both simulated and in vivo tag data. 

PMID- 24110704
TI  - Robust estimation of MRI myocardial perfusion parameters.
AB  - Myocardial perfusion imaging by first-pass contrast-enhanced magnetic resonance
      allows to asses the viability of a tissue by the study of the contrast agent
      transit through the cardiac chambers and myocardium. Since visual inspection is
      difficult and may left aside critical temporal information, the need of automatic
      quantitative analysis arises. We propose two robust estimators of the parameters
      that quantify the perfusion according to a prior pharmacokinetic model. The
      estimators are based on the concentration of the contrast agent inside the tissue
      and the blood. 

PMID- 24110706
TI  - Noninvasive 3D pressure calculation from PC-MRI via non-iterative harmonics-based
      orthogonal projection: constant flow experiment.
AB  - Use of phase-contrast (PC) MRI in assessment of hemodynamics has significant
      clinical importance. In this paper we develop a novel approach to determination
      of hemodynamic pressures. 3D gradients of pressure obtained from Navier-Stokes
      equation are expanded into a series of orthogonal basis functions, and are
      subsequently projected onto an integrable subspace. Before the projection step
      however, a scheme is devised to eliminate the discontinuity at the vessel and
      image boundaries. In terms of the computation time, the proposed approach
      significantly improves on previous iterative methods for pressure calculations.
      The method has been validated using computational fluid dynamic simulations and
      in-vitro MRI studies of stenotic flows.

PMID- 24110707
TI  - Analysis of reliability metrics and quality enhancement measures in current
      density imaging.
AB  - Low frequency current density imaging (LFCDI) is a magnetic resonance imaging
      (MRI) technique which enables calculation of current pathways within the medium
      of study. The induced current produces a magnetic flux which presents itself in
      phase images obtained through MRI scanning. A class of LFCDI challenges arises
      from the subject rotation requirement, which calls for reliability analysis
      metrics and specific image registration techniques. In this study these
      challenges are formulated and in light of proposed discussions, the reliability
      analysis of calculation of current pathways in a designed phantom and a pig heart
      is presented. The current passed is measured with less than 5% error for phantom,
      using CDI method. It is shown that Gauss's law for magnetism can be treated as
      reliability metric in matching the images in two orientations. For the phantom
      and pig heart the usefulness of image registration for mitigation of rotation
      errors is demonstrated. The reliability metric provides a good representation of
      the degree of correspondence between images in two orientations for phantom and
      pig heart. In our CDI experiments this metric produced values of 95% and 26%, for
      phantom, and 88% and 75% for pig heart, for mismatch rotations of 0 and 20
      degrees respectively. 

PMID- 24110708
TI  - Performance evaluation of point matching algorithms for left ventricle motion
      analysis in MRI.
AB  - Finding correspondences between contour points in consecutive frames is crucial
      for the left ventricular motion analysis. In many medical applications, point
      correspondences can be determined by using distinctive anatomical features,
      called anatomical landmarks. However, in the case of cardiac images, these
      landmarks are scarce and insufficient for the registration. Several methods have
      been proposed using semi-landmarks, but this may lead to incorrect
      correspondences. This paper proposes and evaluates the performance of three point
      matching algorithm. Results show that the matching by resampling method leads to
      the best overall correspondences and compares favorably with the performance of a
      state of the art shape alignment algorithm [9]. 

PMID- 24110709
TI  - Evaluation of somatosensory cortical differences between flutter and vibration
      tactile stimuli.
AB  - In parallel with advances in haptic-based mobile computing systems, understanding
      of the neural processing of vibrotactile information becomes of great importance.
      In the human nervous system, two types of vibrotactile information, flutter and
      vibration, are delivered from mechanoreceptors to the somatosensory cortex
      through segregated neural afferents. To investigate how the somatosensory cortex
      differentiates flutter and vibration, we analyzed the cortical responses to
      vibrotactile stimuli with a wide range of frequencies. Specifically, we examined
      whether cortical activity changed most around 50 Hz, which is known as a boundary
      between flutter and vibration. We explored various measures to evaluate
      separability of cortical activity across frequency and found that the hypothesis
      margin method resulted in the greatest separability between flutter and
      vibration. This result suggests that flutter and vibration information may be
      processed by different neural processes in the somatosensory cortex. 

PMID- 24110710
TI  - On the least-square estimation of parameters for statistical diffusion weighted
      imaging model.
AB  - Statistical model for diffusion-weighted imaging (DWI) has been proposed for
      better tissue characterization by introducing a distribution function for
      apparent diffusion coefficients (ADC) to account for the restrictions and
      hindrances to water diffusion in biological tissues. This paper studies the
      precision and uncertainty in the estimation of parameters for statistical DWI
      model with Gaussian distribution, i.e. the position of distribution maxima (Dm)
      and the distribution width (sigma), by using non-linear least-square (NLLS)
      fitting. Numerical simulation shows that precise parameter estimation,
      particularly for sigma, imposes critical requirements on the extremely high
      signal-to-noise ratio (SNR) of DWI signal when NLLS fitting is used.
      Unfortunately, such extremely high SNR may be difficult to achieve for the normal
      setting of clinical DWI scan. For Dm and sigma parameter mapping of in vivo human
      brain, multiple local minima are found and result in large uncertainties in the
      estimation of distribution width sigma. The estimation error by using NLLS
      fitting originates primarily from the insensitivity of DWI signal intensity to
      distribution width sigma, as given in the function form of the Gaussian-type
      statistical DWI model. 

PMID- 24110711
TI  - Quantitative performance assessments for neuromagnetic imaging systems.
AB  - We have developed a Monte-Carlo simulation method to assess the performance of
      neuromagnetic imaging systems using two kinds of performance metrics: A-prime
      metric and spatial resolution. We compute these performance metrics for virtual
      sensor systems having 80, 160, 320, and 640 sensors, and discuss how the system
      performance is improved, depending on the number of sensors. We also compute
      these metrics for existing whole-head MEG systems, MEGvisionTM (Yokogawa Electric
      Corporation, Tokyo, Japan) that uses axial-gradiometer sensors, and TRIUXTM
      (Elekta Corporate, Stockholm, Sweden) that uses planar-gradiometer and
      magnetometer sensors. We discuss performance comparisons between these
      significantly different systems. 

PMID- 24110712
TI  - Residual coherence and residual envelope correlation in MEG/EEG source-space
      connectivity analysis.
AB  - Source-space coherence analysis has become a popular method to estimate
      functional connectivity based on MEG/EEG. One serious problem is that source
      space coherence analysis can be confounded by spurious coherence caused due to
      the leakage properties of the inverse algorithm employed. Such spurious coherence
      is typically manifested as an artifactual large peak around the seed voxel,
      called seed blur, in the resulting coherence images. This seed blur often
      obscures important details of brain interactions. A novel method of computing
      coherence, called the residual coherence, is first proposed to remove the
      spurious coherence caused by the leakage of an imaging algorithm. We then present
      a theoretical analysis that shows the equivalence between the proposed residual
      coherence and corrected imaginary coherence proposed by others. We next extend
      the idea of residual coherence, and propose residual envelope correlation, which
      is suitable for estimating connectivity from high-frequency brain activities.
      Results from computer simulations demonstrate the effectiveness of the residual
      coherence and the residual envelope correlation. 

PMID- 24110713
TI  - Neuromagnetic auditory steady state response to chords: effect of frequency
      ratio.
AB  - Perceptual degree of consonance or dissonance of a chord is known to be varied as
      a function of frequency ratio between tones composing the chord. It has been
      indicated that generation of a sense of dissonance is associated with the
      auditory steady-state response (ASSR) phase-locked to difference frequencies
      which are salient in the chords with complex frequency ratios. This study further
      investigated how the neuromagnetic ASSR would be modulated as a function of the
      frequency ratio when the acoustic properties of the difference frequency, to
      which the ASSR was synchronized, was identical in terms of its number, energy and
      frequency. Neuronal frequency characteristics intrinsic to the ASSR were
      compensated by utilizing responses to a SAM (Sinusoidally Amplitude Modulated)
      chirp tone sweeping through the corresponding frequency range. The results showed
      that ASSR was significantly smaller for the chords with simple frequency ratios
      than for those with complex frequency ratios. It indicates that the basic
      neuronal correlates underlying the sensation of consonance/dissonance might be
      associated with the attenuation rate applied to encode the input information
      through the afferent auditory pathway. Attentional gating of the thalamo-cortical
      function might also be one of the factors. 

PMID- 24110714
TI  - Steady-State Visually Evoked Fields (SSVEF) associated with affective emotions.
AB  - The aim of this study was to examine the SSVEFs associated with the processing of
      positive and negative impression images. We used the International Affective
      Picture System (IAPS) which is increasingly used in brain imaging studies to
      examine emotional processes. Their images also allow valence to be systematically
      investigated. All 200 images were categorized into three categories of "negative
      ", "positive " and "neutral " individually according to valence assessed by each
      subject after the MEG measurement. The peripheral square, i.e., frame, of the
      image was flickered black and white at 15 Hz while the image was kept stationary.
      Those images were randomly presented for 2.0 s on screen set at 120 cm in front
      of the subject. Ten healthy subjects participated. MEG recordings were made with
      a 122-channel whole-head MEG system in a magnetically shielded room. We made two
      dipoles estimation of the averaged MEG signals and obtained the amplitude of
      souse waveform in 15 Hz component (using a band-pass filter at 14-16 Hz) of SSVEF
      in occipital area. The amplitude of the SSVEF source in the occipital area was
      larger for the negative impression images than the positive impression images
      (p<0.05). This result suggests that the amplitude of SSVEF that originated from
      the surrounding field of visual object was modulated by the emotional object and
      that the SSVEF could be a measure of emotion of subjects.

PMID- 24110715
TI  - Spinal cord evoked magnetic field measurement using a magnetospinography system
      equipped with a cryocooler.
AB  - We have developed a magnetospinography (MSG) system that detects weak magnetic
      fields associated with spinal cord neural activity using an array of low
      temperature superconducting quantum interference device (SQUID)-based magnetic
      flux sensors. A functional image of the spinal cord can be obtained noninvasively
      by using this system, and it is effective for precise lesion localization in the
      diagnosis of spinal cord diseases. The running cost of the developed MSG system
      mainly depends on liquid helium (LHe) consumption, which is required to maintain
      the superconducting state of the SQUID sensors. To reduce the LHe consumption, we
      incorporate a pulse-tube-refrigerator-based cryocooler into the MSG system. Cold
      gaseous helium is circulated between the cryocooler and the MSG system for
      cooling the thermal radiation shield of the dewar vessel. Consequently, we
      achieved a 46% decrease in the LHe consumption rate. Conventional biomagnetic
      field detection such as magnetoencephalography is often hindered by severe low
      frequency band noise from the cryocooler. However, in the case of MSG
      measurements, such noise can be filtered out because the band of the signal is
      much higher than that of the cryocooler noise. We demonstrated that the signal-to
      noise ratio of the cervical spinal cord evoked magnetic field measurement
      performed with a working cryocooler is comparable to that of the measurement
      without a cryocooler. 

PMID- 24110716
TI  - Computer-aided diagnosis in endoscopy: a novel application toward automatic
      detection of abnormal lesions on magnifying narrow-band imaging endoscopy in the
      stomach.
AB  - Gastric cancer is the fourth common cancer and the second major cause of cancer
      death worldwide. Early detection of gastric cancer by endoscopy surveillance is
      actively investigated to improve patient survival, especially using the newly
      developed magnifying narrow-band imaging endoscopy in the stomach. However,
      meticulous examination of the aforementioned images is both time and experience
      demanding and interpretation could be variable among different doctors, which
      hindered its widespread application. In this study, we developed a new image
      analysis system by adopting local binary pattern and vector quantization to
      perform pattern comparison between known training abnormal images and testing
      images of magnifying narrow band endoscopy images in the stomach. Our preliminary
      results demonstrated promising potential for automatically labeled region of
      interest for endoscopy doctors to focus on abnormal lesions for subsequent
      targeted biopsy, with the rates of recall 0.46-1.00 and precision 0.39-0.87. 

PMID- 24110718
TI  - Fast identification & modelling of osteoarthritic holes in the human knee with
      contour interpolated radial basis functions.
AB  - In this article, we propose a new method for the fast 3D reconstruction of
      simulated osteoarthritic holes in a human patella. Initially, clean patella
      slices were extracted from MRI scans of the knee using Region-Based Segmentation
      (region-growing) and Bounding Box techniques. Osteoarthritic (OA) holes were then
      simulated in the patella slices. Our contour interpolation/RBF (CI/RBF) method
      was then used to detect the hole automatically and reconstruct 3D models of both
      the patella and OA hole separately. The method presented here proves fast,
      reliable and efficient for reconstructing a 3D model of the patella from MRI
      images with an extremely low error of 0.33%. 

PMID- 24110719
TI  - A novel endoscopic spectral imaging platform integrating k-means clustering for
      early and non-invasive diagnosis of endometrial pathology.
AB  - We report a multimodal endoscopic system capable of performing both color and
      fast multispectral imaging in the spectral range 400-1000 nm. The system is based
      on a computer controllable tunable light source, which can be coupled with all
      types of endoscopes. Performance evaluation showed about 60% flat transmittance
      in almost all the operating wavelengths, at about 13 nm bandwidth per tuning
      step. With this system adapted to a thin hysteroscope, we also report, for the
      first time, spectral analysis of the endometrium and unsupervised/objective
      clustering of the spectra. We have implemented a method combining the k-means
      algorithm with the silhouette criterion for estimating the number of the
      distinguishable spectral classes that may correspond to different medical
      conditions of the tissue. It was found that there are five-well defined clusters
      of spectra, while preliminary clinical data seem to correlate well with the
      tissue pathology.

PMID- 24110720
TI  - Ciliary motility activity measurement using a dense optical flow algorithm.
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. In this study, an automatic method has been established to determine the
      ciliary motility activity from cell cultures by means of optical flow
      computation, and has been applied to 136 control cultures and to 144 RSV-infected
      cultures. The control group presented an average of cell surface with cilia
      motility per field of 41 +/- 15 % (mean +/- standard deviation), while the
      infected group presented a 11 +/- 5 %, t-Student p<0.001. The cutoff value to
      classify a infected specimen was <17.89 % (sensitivity 0.94, specificity 0.93).
      This methodology has proved to be a robust technique to evaluate cilia motility
      in cell cultures.

PMID- 24110722
TI  - Development of a numerical simulator of human swallowing using a particle method
      (part 1. Preliminary evaluation of the possibility of numerical simulation using
      the MPS method).
AB  - The aim of the present study was to evaluate the possibility of numerical
      simulation of the swallowing process using a moving particle simulation (MPS)
      method, which defined the food bolus as a number of particles in a fluid, a
      solid, and an elastic body. In order to verify the accuracy of the simulation
      results, a simple water bolus falling model was solved using the three
      dimensional (3D) MPS method. We also examined the simplified swallowing
      simulation using a two-dimensional (2D) MPS method to confirm the interactions
      between the liquid, solid, elastic bolus, and organ structure. In a comparison of
      the 3D MPS simulation and experiments, the falling time of the water bolus and
      the configuration of the interface between the liquid and air corresponded
      exactly to the experimental measurements and the visualization images. The
      results showed that the accuracy of the 3D MPS simulation was qualitatively high
      for the simple falling model. Based on the results of the simplified swallowing
      simulation using the 2D MPS method, each bolus, defined as a liquid, solid, and
      elastic body, exhibited different behavior when the organs were transformed
      forcedly. This confirmed that the MPS method could be used for coupled
      simulations of the fluid, the solid, the elastic body, and the organ structures.
      The results suggested that the MPS method could be used to develop a numerical
      simulator of the swallowing process. 

PMID- 24110723
TI  - Toward reducing uncertainty in Fluorescence Recovery After Photobleaching.
AB  - We investigate the uncertainty associated with the Fluorescence Recovery After
      Photobleaching, FRAP, which is widely used in the determination of diffusion
      coefficient for bio molecules. The uncertainty of our FRAP technique stems from
      the measurement of the spot size and the half time. The uncertainties of the FRAP
      is evaluated by considering the uncertainty propagation through the measurements
      of both spot size and the half time. Finally, we suggest an approach to estimate
      the effective diffusion coefficient by considering slip conditions between the
      fluorescent beads and the fluid. The diffusion coefficients measured by the FRAP
      is close to those obtained from the Stokes-Einstein relation together with the
      slip correction factor rather than that obtained solely by the Stokes-Einstein
      equation. 

PMID- 24110724
TI  - Separation method of blood constituents using dielectrophoresis and flow-induced
      shear force.
AB  - Platelet Rich Plasma (PRP) contains many cytokines for treatment skin diseases.
      The final goal of this study is to develop the dielectrophoretic PRP purification
      system enriching the platelets in a label-free manner from whole blood solution.
      In this study, we characterized dielectrophoretic properties of red blood cell,
      white blood cell, and platelet for the fundamental study. Moreover, purification
      of PRP was performed to eliminate red and white blood cells using
      dielectrophoretic and flow-induced shear force. 

PMID- 24110725
TI  - High throughput cell sorting device using dielectrophoresis and fluid-induced
      shear force.
AB  - Cell sorting is important technology in many areas such as medical diagnosis in
      hospitals and cell engineering. Dielectrophoresis (DEP) is one of the promising
      approaches for cell separation because it does not require any fluorescent dye or
      antibody. In our previous study, we developed DEP cells sorting device, however
      the amount of throughput was not sufficient. In this study, we developed high
      throughput cell sorting device using dielectrophoretic and fluid-induced shear
      force. As the pilot study, mixed solution containing bovine chondrocytes and
      polystyrene beads were precisely separated using our novel DEP cell sorting
      device. 

PMID- 24110726
TI  - Detection of stress hormones by a microfluidic-integrated polycarbazole/fullerene
      photodetector.
AB  - A novel photodetector integrated microfluidic system for chemiluminescence (CL)
      detection is reported. The system incorporates a polycarbazole/fullerene
      photodiode whose optical characteristics (i.e. dark current, external quantum
      efficiency and photosensitivity) are described here. Using a CL immunoassay for
      detecting the stress hormone cortisol, the integrated photodetector achieved a
      detection sensitivity of 1.775 pA * nM(-1) and a detection limit of less than
      0.28 nM. The device would be a powerful low-cost alternative to silicon
      photodiode and photomultiplier tube for bioanalytical assays, with potentially
      wide-ranging applications within point-of-care diagnostics. 

PMID- 24110727
TI  - Microfluidic cell culture system with on-chip hypoxic conditioning.
AB  - We have demonstrated a portable microfluidic cell culture system with multi-gas
      (CO2 and O2) incubation which we can cultivate under hypoxia without bulky
      peripheral apparatus such as gas tanks, regulators, and flow controllers. The
      system contains a chip of 26 mm * 48 mm which is capable to diffuse CO2 and
      absorb O2 through a gas-permeable wall of nested media reservoir. The media was
      water-jacketed with aqueous solution containing 0.8 M sodium bicarbonate as CO2
      supply and 1 M sodium ascorbate as oxygen scavenger. The partial CO2 pressure
      (pCO2) in media reservoir stabilized at least 10.2% +/- 0.11% for at least 72
      hours. The partial O2 pressure (pO2) in the media reservoir decreased to 4.2%.
      Portable on-chip hypoxic culture of SV40-T2 cells for 72 h was also demonstrated.

PMID- 24110728
TI  - Measurement of subcutaneous biological substances using thin metal needle with
      micro flow channel.
AB  - Concentrations of biological substances are useful as indicators of physiological
      and pathological states. In order to monitor biological substances in daily life,
      we developed a minimally invasive needle type device with which biological
      substances are extracted through a microperfusion system inserted under the skin.
      The perfusion needle has a flow channel with perforated membrane through which
      biological substances from subepidermal tissue are extracted. The efficacy of the
      device was examined by measuring lactate concentration of exercising mice.
      Lactate was successfully collected from the back skin of the mice running on a
      treadmill using a fabricated microperfusion needle. Lactate concentration of
      perfused solution correlated with blood lactate concentration. 

PMID- 24110729
TI  - Light-induced microbubble poration of localized cells.
AB  - Molecular delivery into localized NIH/3T3 cells was achieved with microbubbles
      produced by laser pulses focused on an optically absorbent substrate. The laser
      induced bubble expansion and contraction resulted in cell poration. The
      microbubbles are localized at the laser focal point, so molecular delivery can be
      directed at specific localized cells. This was demonstrated with the delivery of
      3-kDa FITC-Dextran. Single-cell molecular delivery was achieved, even in the
      presence of nearby cells. The efficiency of the cell poration was up to 95%, with
      a corresponding cell viability of 98%. 

PMID- 24110731
TI  - A grasping forceps with a triaxial MEMS tactile sensor for quantification of
      stresses on organs.
AB  - This paper reports on a grasping forceps with a triaxial Micro Electro Mechanical
      Systems (MEMS) tactile sensor on a tip. The laparoscopic surgery is minimally
      invasive because the incisions are smaller than the open surgery. This results in
      fast recovery. However, it is a problem in the laparoscopic surgery to damage an
      organ by localized stress generated by grasping with a thin forceps. To avoid
      excessive stress applying to the organ, real time evaluation of the stress is
      important. However, there is no acceptable tool to measure the stress. We propose
      a grasping forceps with a triaxial MEMS tactile sensor on a tip for a measurement
      tool. We attached a triaxial MEMS tactile sensor which we have developed on a tip
      of a grasping forceps. The MEMS sensor can measure not only the pressure but also
      two directional shear stresses applied to the sensor surface. The sensor size is
      7 mm * 7 mm * 2 mm. It is enough small to attach the sensor to the tip of a
      forceps 12 mm in diameter. In this paper, the characteristics of the forceps with
      the MEMS sensor during grasping, pushing and pulling actions were evaluated. In
      these experiments, output of each sensor for pressure and shear stress was
      proportional to the applied stresses, respectively. Moreover, as an in vivo
      experiment, we measured the shear stress applied to a pig liver block when it is
      lifted after being grasped with the forceps. We obtained that the shear stress
      applied to the liver block increased with the increase of the weight of the liver
      block. 

PMID- 24110733
TI  - Expression of c-erbB-2 in breast cancer cell lines as experimental receptor of
      magnetic nanoparticles.
AB  - High mortality in breast cancer is associated to a late diagnosis and therapy of
      the disease. Our research group is working on the development of an innovative
      technology to promote selective ablation of breast cancer in early stages by the
      use of high frequency magnetic fields assisted by magnetic nanoparticles. The
      concept behind the technical proposal is to increase the electrical conductivity
      of tumoral tissue by the use of bioconjugated "magnetic nanoparticle-monoclonal
      antibody". Is expected that bioconjugated recognizes specific genes on the
      surface of cancer cells. The aim of this study was to evaluate the expression of
      the c-erbB-2 gene and c-erbB-2 antigen in breast cancer cells type BT-474, MCF-7
      and MDA-MB-231, as previous step to propose the c-erbB-2 protein as receptor of
      magnetic nanoparticles. The results suggest that the elected breast cancer cell
      lines show well-differentiated relative expression of the elected gen and
      antigen, and sems suitable for experimental evaluation of selective targeting by
      magnetic nanoparticles. 

PMID- 24110734
TI  - Interfacing neurons through the patch membrane pierced with single-walled carbon
      nanotubes.
AB  - The usability of single-walled carbon nanotubes (CNTs) as electrically conductive
      channels across the cell membrane was examined at the submicroscopic level. By
      using the patch-clamp technique, we found the surface-modified single-walled CNTs
      dispersed in the micropipette solution can provide an electrical access to the
      intracellular space across the patch of cell membrane in dissociated mammalian
      neurons, thereby enabling us to measure the membrane excitabilities in the
      'pierced-patch' whole-cell mode. 

PMID- 24110735
TI  - Multiple reaction analysis of cancer with different markers using silicon
      nanowire FET.
AB  - In this study, we have used newly developed Silicon nanowire (SiNW) arrays to
      evaluate their feasibility for the quantification of different markers of
      interests. We have quantified four different markers of PSA, EGF, IL-6, and VDBP.
      Each marker showed measurements in the range of 0.184~17.79 ng/mL (PSA), 10
      pg/mL~10 ng/mL (EGF), 10 pg/mL~50 ng/mL (IL-6), and 10 pg~5 ng/mL (VDBP),
      respectively. For the experiment, we collected 10 different serum samples, 5
      prostate cancer patients and 5 breast cancer patients, and measured and compared
      the resulting signal from the SiNW FET to serum sample from normal patients. As a
      result, we observed a meaningful pattern of markers associated with each type of
      cancer. In addition, we have measured the response signal of SiNWs conjugated
      with Epithelial cell adhesion molecules (EpCAM) markers against tumor cells as
      they interacted with those markers.

PMID- 24110736
TI  - Urine glucose analysis with functionalized graphene oxide as a material for
      amperometric sensor.
AB  - New functionalized graphene oxide (FGO) was systematically coated on the
      fabricated Au-PCB for the detection of glucose in urine. The electrical response
      of FGO-Au-PCB exhibited a wide linearity of 1.7~44.4 mM of glucose levels and a
      constant variables was less than 3% of the previously performed multiple
      measurements. The practical application has been demonstrated by measuring the
      electrical response against glucose in urine samples. In addition, our findings
      show similar improvement in urine glucose; within each current level, there were
      significant improvements in urine glucose. Comparison between the urine glucose
      and blood glucose showed no significant different level from the same subjects.

PMID- 24110737
TI  - Three-dimensional modeling of oxidized-LDL accumulation and HDL mass transport in
      a coronary artery: a proof-of-concept study for predicting the region of
      atherosclerotic plaque development.
AB  - Low density lipoprotein (LDL) has a significant role on the atherosclerotic
      plaque development, while the concentration of high density lipoproteins (HDL) is
      considered to play an atheroprotective role according to several biochemical
      mechanisms. In this work, it is the first time that both LDL and HDL
      concentrations are taken into account in order to predict the regions prone for
      plaque development. Our modeling approach is based on the use of a realistic
      three-dimensional reconstructed pig coronary artery in two time points.
      Biochemical data measured in the pig were also included in order to develop a
      more customized model. We modeled coronary blood flow by solving the Navier
      Stokes equations in the arterial lumen and plasma filtration in the arterial wall
      using Darcy's Law. HDL transport was modeled only in the arterial lumen using the
      convection-diffusion equation, while LDL transport was modeled both in the lumen
      and the arterial wall. An additional novelty of this work is that we model the
      oxidation of LDL taking into account the atheroprotective role of HDL. The
      results of our model were in good agreement with histological findings
      demonstrating that increased oxidized LDL is found near regions of advanced
      plaques, while non-oxidized LDL is found in regions of early plaque types. 

PMID- 24110738
TI  - Dynamic mechanical finite element model of biological cells for studying cellular
      pattern formation.
AB  - Understanding the geometric, topologic, and mechanical properties of cells and
      their interactions is critical for studying tissue pattern formation and organ
      development. Computational model and tools for simulating cell pattern formation
      have broad implications in studying embryogenesis, blood-vessel development,
      tissue regeneration, and tumor growth. Although a number of cell modeling methods
      exist, they do not simultaneously account for detailed cellular shapes as well as
      dynamic changes in cell geometry and topology. Here we describe a dynamic finite
      element cell model (dFEMC) for studying populations of cells and tissue
      development. By incorporating details of cell shape, cell growth and shrinkage,
      cell birth and death, cell division and fusion, our method can model
      realistically a variety problems of cell pattern formation. We give two examples
      of applying our method to the study of cell fusion and cell apoptosis. The dFEMC
      model developed here provides a general computational framework for studying
      dynamics pattern formation of tissue. 

PMID- 24110739
TI  - Estimation of shear-stress-induced endothelial nitric oxide production from flow
      mediated dilation.
AB  - Vascular endothelial function assessment yields important diagnostic and
      prognostic information on patients with (or at risk of) cardiovascular diseases.
      Flow-mediated dilation (FMD) is the most widely used noninvasive method for
      assessing the endothelial function. In this method, the magnitude of FMD is used
      as a surrogate marker for the endothelial function. However, because vasodilation
      is affected by several other factors as well, the details of how this marker
      represents the endothelial function are not fully understood. Previously, we
      developed a mathematical model for vasodilation with intra- and intercellular
      pathways. In this study, we estimated the shear-stress-induced endothelial nitric
      oxide production from FMD measurements using the model. The results suggested
      that the accuracy of the estimated endothelial function obeys the characteristics
      of the shear stress added to the vascular wall. Furthermore, we showed that the
      FMD response describes not only the endothelial function but also vascular wall
      characteristics. 

PMID- 24110740
TI  - Exposure of high resolution fetuses in advanced pregnant woman models at
      different stages of pregnancy to uniform magnetic fields at the frequency of 50
      Hz.
AB  - Extremely low frequency magnetic fields (ELF-MF) have been considered as a
      possible risk factor for childhood leukemia by several epidemiological studies.
      In this work the exposure assessment of fetuses at 3, 7 and 9 months of
      Gestational Age (GA) to differently polarized uniform magnetic fields at the
      frequency of 50 Hz by means of high resolution numerical models of pregnant women
      is carried out. This set of models is used to analyze the fetal tissue-specific
      induced electric fields and current densities as a function of both the incident
      magnetic field polarization and the GA. 

PMID- 24110741
TI  - A tumor-immune mathematical model of CD4+ T helper cell dependent tumor
      regression by oncogene inactivation.
AB  - Understanding the complex dynamics between the tumor cells and the host immune
      system will be key to improved therapeutic strategies against cancer. We propose
      an ODE-based mathematical model of both the tumor and immune system and how they
      respond to inactivation of the driving oncogene. Our model supports experimental
      results showing that cellular senescence of tumor cells is dependent on CD4+ T
      helper cells, leading to relapse of tumors in immunocompromised hosts. 

PMID- 24110742
TI  - An intelligent flow control system for long term fluid restriction in small
      animals.
AB  - Fluid retention is one of the most common symptoms in patients with chronic heart
      failure. Although fluid restriction may be a therapeutic strategy, the degree of
      fluid restriction necessary for the best therapeutic outcome remains unknown
      partly due to the lack of proper experimental method to restrict water
      consumption in small animals. The traditional methods that allow animals to
      access water only in a limited time window or within pre-determined daily volume
      can be stressful because the animals may become thirsty during the time of water
      deprivation. To provide a less stressful water restriction paradigm, we designed
      a feedback-control system of drinking flow to modulate the drinking behavior of
      small animals. This system consisted of an infrared droplet sensor for monitoring
      the drinking flow and a computer controlled electric valve to regulate the water
      availability. A light signal which synchronized with the command for opening the
      valve was set to establish a conditioned reflex. An animal test indicated that
      rats were adaptable to a precisely programmed water supply. This system may
      warrant investigation into the consequences of fluid restriction in chronic
      experimental animal study. 

PMID- 24110743
TI  - 2D data-driven stalk cell prediction model based on tip-stalk cell interaction in
      angiogenesis.
AB  - Angiogenesis is the growth process of blood vessels from existing vessels. During
      angiogenesis, endothelial cells (ECs), which line the vessel, specialize into tip
      and stalk cells. Tip cells respond to angiogenic signals, burrow into the
      extracellular matrix (ECM) and form conduits. Stalk cells follow the tip cells
      along the conduits, and form solid sprouts or lumen vessels. Interactions between
      stalk cells and tip cells are important for creating functional vessels. The goal
      of this work is to predict stalk cells migration trajectories from known tip cell
      trajectories. Four factors influence the position and velocity of cell migration
      in ECM: cell-cell interaction, drag force, chemotactic signal and cell-ECM
      interaction. As chemotactic signal and cell-ECM interactions have little effect
      on stalk cell movement, the proposed model includes the influence of cell-cell
      interactions and drag force only. The unknown parameters in the model are
      inferred by Maximum Likelihood Estimation (MLE) from experimental time-lapse cell
      migration data. Numerical results suggest that the proposed model can accurately
      predict stalk cell trajectories. The proposed model may be useful for the study
      of angiogenesis, a critical process for cancer tumor growth. 

PMID- 24110744
TI  - Functional simulation of the cochlea for implant optimization.
AB  - Cochlear implantation is a surgical technique which aims to restore hearing in
      people with deep hearing loss. However, outcomes of the surgery still exhibit a
      large variability between patients. Among the factors that contribute to
      variability the most important are morphological differences in anatomical
      structures between patients and incorrect implant placements. In order to address
      these issues, it would be desirable to have a functional model of the cochlea
      which incorporates inter-patients variability and simulate electrode placement.
      To this end, we present a finite element model which captures the interaction
      between the cochlear partition, modeled as an elastic solid with finite
      deformation, and the perilymph fluid, modeled as a compressible, viscous fluid.
      Numerical results show that the membrane responds to changes in the stimulation
      frequencies. 

PMID- 24110745
TI  - Implementation of a gelatin model to simulate biological activity in the inner
      ear for electrovestibulography (EVestG) validation.
AB  - In this work, a physical model that simulates electrical activity of the inner
      ear has been developed. The purpose is to evaluate extraction of vestibular field
      potentials (FPs) in the presence of various sources of noise by a proprietary
      software algorithm. The ear model is constructed of gelatin as an alternative to
      human tissue where independently driven electrical sources are placed in gelatin
      to mimic various biological signals (muscle, cerebral, and vestibular).
      Components of system noise (recording apparatus generated noise, electrodes, etc)
      will be naturally superimposed on the recording, hence enables various recording
      conditions to be simulated. Muscle activity present in the recordings and noise
      generated from the recording apparatus were found to be the most dominating
      sources that degrade performance of FP extraction. The model can be used to
      provide insights towards enhancing the FP detection algorithm under various
      signal-to-noise ratios. 

PMID- 24110746
TI  - Statistical analysis of tracheal breath sounds during wakefulness for screening
      obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a prevalent disorder. The accepted method of
      diagnosis in widespread clinical practice, polysomnography (PSG), is costly and
      very time consuming; therefore, quick screening methods, especially when there is
      a need for quick diagnosis, is of great interest. Diagnostic methods which
      exploit subtle differences in breath sounds recorded during wakefulness, such as
      our group's Awake-OSA technology, have shown their capability to diagnose OSA at
      the research stage. Simplifying the breath sound recording procedure employed in
      the Awake-OSA diagnostic method would increase its efficiency when used in a
      clinical setting. In this study, we adopted breath sound data collected during
      wakefulness in two positions (sitting upright and supine) and two breathing
      maneuvers (nose and mouth breathing) from our previous study, and ran hypothesis
      tests on a wide variety of sound features to select the most significant features
      correlated with OSA. The goal was to investigate which combinations of patient
      position and breathing maneuver contribute the least to the significant features
      amongst groups of people with differing OSA severity, thus permitting
      simplification of the recording protocol. The results show that all signals
      recorded by a combination of the two breathing maneuvers and two positions result
      in features significantly correlated with OSA severity; this makes it impossible
      to confidently recommend that a combination be omitted from the recording
      protocol. Nevertheless, the results show that the majority of significant
      features originated from recordings made in the supine position. Therefore, as a
      step toward simplification of the Awake-OSA diagnostic algorithm, we may use
      breath sound signals recorded only in the supine position and further investigate
      the accuracy of the algorithm in distinguishing amongst groups with differing OSA
      severity.

PMID- 24110747
TI  - Influence of cell morphology in a computational model of ON and OFF retinal
      ganglion cells.
AB  - We developed anatomically and biophysically detailed ionic models to understand
      how cell morphology contributes to the unique firing patterns of ON and OFF
      retinal ganglion cells (RGCs). With identical voltage-gated channel kinetics and
      distribution, cell morphology alone is sufficient to generate quantitatively
      distinct electrophysiological responses. Notably, recent experimental
      observations from ON and OFF RGCs can be closely reproduced by the variations in
      their cell morphologies alone. Our results suggest that RGC morphology in
      conjunction with biophysical properties and network connectivity are able to
      produce the diverse response repertoire of RGCs. 

PMID- 24110748
TI  - Influence of active dendrites on firing patterns in a retinal ganglion cell
      model.
AB  - Active regional conductances and inhomogeneous distribution of membrane ionic
      channels in dendrites influence the integration of synaptic inputs in cortical
      neurons. How these properties shape the response properties of retinal ganglion
      cells (RGC) in the mammalian retina has remained largely unexplored. In this
      study, we used a morphologically-realistic RGC computational model to study how
      active dendritic properties contribute to neural behaviors. Our simulations
      suggest that the dendritic distribution of voltage-gated ionic channels strongly
      influences RGC firing patterns, indicating their important contribution to
      neuronal function. 

PMID- 24110749
TI  - New trends in computational modeling: a Neuroid-based retina model.
AB  - It is thought that using detailed neuron-models could lead to a better
      understanding of how the nervous system works. However, neural networks preserve
      their collective computational properties, regardless of the level of description
      used for modeling the main building block. In this paper, we built a Neuroid
      based retina model. As a result of the implementation, the Neuroid was able to
      reproduce the essential features of the photoreceptor response to light.
      Likewise, the retina model responded to specific visual effects such as
      simultaneous contrast, Mach bands and Hermann grid. All of these suggest that the
      Neuroid comprises enough functional characteristics, such that we could focus not
      only on the most relevant computational aspects of nerve cells, but also in the
      collective capabilities of large-scale neural networks. 

PMID- 24110750
TI  - Influence of the anisotropic mechanical properties of the skull in low-intensity
      focused ultrasound towards neuromodulation of the brain.
AB  - Lately, neuromodulation of the brain is considered one of the promising
      applications of ultrasound technology in which low-intensity focused ultrasound
      (LIFU) is used noninvasively to excite or inhibit neuronal activity. In LIFU, one
      of critical barriers in the propagation of ultrasound wave is the skull, which is
      known to be highly anisotropic mechanically: this affects the ultrasound
      focusing, thereby neuromodulation effects. This study aims to investigate the
      influence of the anisotropic properties of the skull on the LIFU via finite
      element head models incorporating the anisotropic properties of the skull. We
      have examined the pressure and stress distributions within the head in LIFU. Our
      results show that though most of the pressure that reaches to the brain is due to
      the longitudinal wave propagation through the skull, the normal stress in the
      transverse direction of the wave propagation has the main role to control the
      pressure profile inside the brain more than the shear stress. The results also
      show that the anisotropic properties of skull contribute in broadening the focal
      zone in comparison to that of the isotropic skull. 

PMID- 24110751
TI  - Real-time rendering of drug injection and interactive simulation of vessel
      deformation using GPU.
AB  - Developing patient specific model for the simulation of chemotherapy drug
      injection is important in medical application. This paper proposed a two-phase
      fluidic method to simulate chemotherapy drug injection and an improved lumped
      element method to simulate deformation of vessel at real-time by using GPU for
      general computing. Firstly, a three-dimensional (3-D) model of hepatic vessels is
      reconstructed from clinical CT-images using multi-layer method. A 3-D thinning
      algorithm based on Valence Driven Spatial Median (VDSM) is applied to generate
      unit-width skeleton of the vessel tree. The two-phase flow simulation of drug
      injection is based on Hagen-Poiseuille model by introducing a friction factor
      using bubbly flow Reynolds number. The improved lumped element method achieves
      good simulation realism at high computational speed to simulate deformable
      object. Real-time rendering and interaction of vessel deformation, self
      collision, and surface tearing has been realized and demonstrated in a virtual
      experiment. 

PMID- 24110752
TI  - Theoretical analysis of body hair movement in ELF electric field exposure in
      different environmental conditions.
AB  - To elucidate the mechanism of the biological effect of ELF (extremely low
      frequency, 0-300 Hz) electric field and to settle appropriate safety standards,
      the body hair movement in AC electric field exposure was analyzed. We derived the
      equation of motion to describe the body hair movement cause by the electric
      force, and obtained an analytic solution for AC input. We applied this solution
      to practical conditions and clarified the body hair movement in AC electric field
      exposure. Using this solution, we analyzed the body hair movement in different
      humidity and verified the validity of the analysis in experiments. 

PMID- 24110753
TI  - Fundamental study on formulation design of skin care products by modeling of
      tactile sensation.
AB  - The objective of this study is to construct a method to quantify and formulate
      the human tactile sensation. We have tried to indicate the sensory scores of
      tactile sensation as a combination of the physical values of skin care products.
      Consequently, the extracted principle factors of the sensory properties could be
      related to the physical values by multiple regression analysis. For the next
      step, we investigated the physical mechanism of tactile sensation, and proposed a
      method to formulate the sensory properties. A method to formulate the sensory
      properties of skin care products was constructed based on the relation between
      sensory values, principal factors, physical values and composition. The method
      was verified by sensory evaluation. 

PMID- 24110754
TI  - Uncertainty modeling of input data for a biomechanical system of systems.
AB  - Biomechanical models simulating pathologies need assumptions and often have to
      deal with data from different sources. We proposed a biomechanical system of
      systems (BSoS) including two modeling (biomechanics and knowledge-based)
      approaches to understand the impact of musculoskeletal pathologies leading to
      propose better diagnosis and appropriate treatment prescription. Moreover,
      uncertainty of input data was modeled leading to quantify their impact on the
      simulation results. The architecture of our BSoS including different constituent
      systems was presented and discussed. Novel knowledge-based fusion p-boxes were
      developed for uncertainty modeling purpose. Case study was performed on the
      musculoskeletal simulation. Discussion was addressed. 

PMID- 24110755
TI  - Facial mimics simulation using MRI and finite element analysis.
AB  - Recent research studies aimed to simulate facial expressions or motions due to
      muscle contraction using biomechanical models ranging from basic to advanced
      muscle constitutive models. However, these models are based on generic geometries
      and there is a lack of experimental data for the numerical simulation as well as
      for the model validation in a clinical context. The objective of our present
      study was to perform facial mimics simulation using subject specific data derived
      from MRI technique. Zygomaticus major muscle is modelled as a transversely
      isotropic hyperelastic material. Then the resulting effect of its shortening and
      lengthening process on the facial mimics simulation was performed using Finite
      Element Analysis. Simulation results were presented and discussed. Such study
      will be of interest for defining objective criteria to evaluate the facial
      disfigurement patients and to perform the functional rehabilitation. 

PMID- 24110756
TI  - Muscle force estimation with surface EMG during dynamic muscle contractions: a
      wavelet and ANN based approach.
AB  - Human muscle force estimation is important in biomechanics studies, sports and
      assistive devices fields. Therefore, it is essential to develop an efficient
      algorithm to estimate force exerted by muscles. The purpose of this study is to
      predict force/torque exerted by muscles under dynamic muscle contractions based
      on continuous wavelet transform (CWT) and artificial neural networks (ANN)
      approaches. Mean frequency (MF) of the surface electromyography (EMG) signals
      power spectrum was calculated from CWT. ANN models were trained to derive the MF
      force relationships from the subset of EMG signals and the measured forces. Then
      we use the networks to predict the individual muscle forces for different muscle
      groups. Fourteen healthy subjects (10 males and 4 females) were voluntarily
      recruited in this study. EMG signals were collected from the biceps brachii,
      triceps, hamstring and quadriceps femoris muscles to evaluate the proposed
      method. Root mean square errors (RMSE) and correlation coefficients between the
      predicted forces and measured actual forces were calculated. 

PMID- 24110757
TI  - A linear model for simultaneously and proportionally estimating wrist kinematics
      from emg during mirrored bilateral movements.
AB  - This paper presents a linear model for simultaneous and proportional estimation
      of the two degree-of-freedoms (DOFs) wrist angle positions with surface
      electromyography (EMG). A 5th order state-space model was used to estimate wrist
      kinematics from 4-channel surface EMG signals of the contralateral forearm during
      mirrored bilateral movements without motion constraints. The EMG signal from each
      of the three limbed normal subjects was collected along with each angle position
      in two DOFs from both of the arms, with motion parameters tested including the
      radial/ulnar deviation and flexion/extension of the wrist. The estimation
      performance was in the range 0.787-0.885 (R(2) index) for the two DOFs in three
      limbed normal subjects. The results show that wrist kinematics can be estimated
      in 2 DOFs by state-space models with relative high accuracy compared with the
      results reported previously. The method proposed, as requiring only kinematics
      measured from the contralateral wrist, is potentially available for a unilateral
      amputee in simultaneous and proportional control of DOFs in powered upper limb
      prostheses. 

PMID- 24110758
TI  - Experimental study on a smart wheelchair system using a combination of
      stereoscopic and spherical vision.
AB  - This paper is concerned with the experimental study performance of a smart
      wheelchair system named TIM (Thought-controlled Intelligent Machine), which uses
      a unique camera configuration for vision. Included in this configuration are
      stereoscopic cameras for 3-Dimensional (3D) depth perception and mapping ahead of
      the wheelchair, and a spherical camera system for 360-degrees of monocular
      vision. The camera combination provides obstacle detection and mapping in unknown
      environments during real-time autonomous navigation of the wheelchair. With the
      integration of hands-free wheelchair control technology, designed as control
      methods for people with severe physical disability, the smart wheelchair system
      can assist the user with automated guidance during navigation. An experimental
      study on this system was conducted with a total of 10 participants, consisting of
      8 able-bodied subjects and 2 tetraplegic (C-6 to C-7) subjects. The hands-free
      control technologies utilized for this testing were a head-movement controller
      (HMC) and a brain-computer interface (BCI). The results showed the assistance of
      TIM's automated guidance system had a statistically significant reduction effect
      (p-value = 0.000533) on the completion times of the obstacle course presented in
      the experimental study, as compared to the test runs conducted without the
      assistance of TIM. 

PMID- 24110759
TI  - Improvement of tactile sensitivity by stochastic resonance effect--applications
      to surgical grasping forceps.
AB  - This paper reports experimental results on a surgical grasping forceps with a
      vibration actuator that enhances a tactile perception ability. A short-time
      exposure of tactile receptors to sub-sensory white-noise vibration is known to
      improve perception ability. This phenomenon, called stochastic resonance (SR) in
      the somatosensory system, is expected to enhance the sense of touch when the weak
      vibration is applied to a fingertip, and thereby improve associated motor skills.
      A lead zirconate titanate (PZT) actuator was attached on the grip of surgical
      grasping forceps. A passive sensory test has been conducted for healthy subjects
      to confirm the efficacy of the device. Statistical significance has been observed
      when appropriate noise is applied. To investigate the effect of the noise
      intensity, a summing network of FitzHugh-Nagumo model neurons was built. The
      simulation results showed that a network with relatively large units can improve
      the detection capability of the input signal. 

PMID- 24110760
TI  - Real-time estimation of tongue movement based on suprahyoid muscle activity.
AB  - In this study, we introduce a real-time method for tongue movement estimation
      based on the analysis of the surface electromyography (EMG) signals from the
      suprahyoid muscles, which usual function is to open the mouth and to control the
      position of the hyoid, the base of the tongue. Nine surface electrodes were
      affixed to the underside of the jaw and their signals were processed via multi
      channel EMG system. The features of the EMG signals were extracted by using a
      root mean square (RMS) method. The dimension of the variables was reduced
      additionally from 108 to 10 by applying the Principal Component Analysis (PCA).
      The feature quantities of the reduced dimension set were associated with the
      tongue movements by using an artificial neural network. Results showed that the
      proposed method allows precise estimation of the tongue movements. For the test
      data set, the identification rate was greater than 97 % and the response time was
      less than 0.7 s. The proposed method could be implemented to facilitate novel
      approaches for alternative communication and control of assistive technology for
      supporting the independent living of people with severe quadriplegia. 

PMID- 24110761
TI  - Influence of the model's degree of freedom on human body dynamics identification.
AB  - In fields of sports and rehabilitation, opportunities of using motion analysis of
      the human body have dramatically increased. To analyze the motion dynamics, a
      number of subject specific parameters and measurements are required. For example
      the contact forces measurement and the inertial parameters of each segment of the
      human body are necessary to compute the joint torques. In this study, in order to
      perform accurate dynamic analysis we propose to identify the inertial parameters
      of the human body and to evaluate the influence of the model's number of degrees
      of freedom (DoF) on the results. We use a method to estimate the inertial
      parameters without torque sensor, using generalized coordinates of the base link,
      joint angles and external forces information. We consider a 34DoF model, a 58DoF
      model, as well as the case when the human is manipulating a tool (here a tennis
      racket). We compare the obtained in results in terms of contact force estimation.

PMID- 24110762
TI  - Comparing "pick and place" task in spatial Augmented Reality versus non-immersive
      Virtual Reality for rehabilitation setting.
AB  - Introducing computer games to the rehabilitation market led to development of
      numerous Virtual Reality (VR) training applications. Although VR has provided
      tremendous benefit to the patients and caregivers, it has inherent limitations,
      some of which might be solved by replacing it with Augmented Reality (AR). The
      task of pick-and-place, which is part of many activities of daily living (ADL's),
      is one of the major affected functions stroke patients mainly expect to recover.
      We developed an exercise consisting of moving an object between various points,
      following a flash light that indicates the next target. The results show superior
      performance of subjects in spatial AR versus non-immersive VR setting. This could
      be due to the extraneous hand-eye coordination which exists in VR whereas it is
      eliminated in spatial AR. 

PMID- 24110763
TI  - Passive-type rehabilitation systems for upper limbs with MR fluid brake and its
      training software.
AB  - It is important to construct rehabilitation system for elderly people, people who
      have suffered strokes, and so on. In recent years, the need for rehabilitation
      support systems is increasing that using force display devices. When using force
      display systems, it is most important to ensure safety mechanically in order to
      prevent operators from hurting. Conventional force display systems are active
      type devices with actuators but these devices may become dangerous when going out
      of control. On the other hand, passive-type force display devices with only
      passive elements are thought to be an effective method for assuring inherent
      safety. In this paper, we evaluate force display ability about a 2-D passive-type
      force display device with fast-response MR (Magneto-Rheological) fluid brakes to
      apply this device to rehabilitation training. 

PMID- 24110764
TI  - Proprioception rehabilitation training system for stroke patients using virtual
      reality technology.
AB  - We investigated a virtual reality (VR) proprioceptive rehabilitation system that
      could manipulate the visual feedback of upper-limb during training and could do
      training by relying on proprioception feedback only. Virtual environments were
      designed in order to switch visual feedback on/off during upper-limb training.
      Two types of VR training tasks were designed for evaluating the effect of the
      proprioception focused training compared to the training with visual feedback. In
      order to evaluate the developed proprioception feedback virtual environment
      system, we recruited ten stroke patients (age: 54.7+/- 7.83years, on set: 3.29+/-
      3.83 years). All patients performed three times PFVE task in order to check the
      improvement of proprioception function just before training session, after one
      week training, and after all training. In a comparison between FMS score and
      PFVE, the FMS score had a significant relationship with the error distance(r = 
      .662, n=10, p = .037) and total movement distance(r = -.726, n=10, p = .018) in
      PFVE. Comparing the training effect between in virtual environment with visual
      feedback and with proprioception, the click count, error distance and total error
      distance was more reduced in PFVE than VFVE. (Click count: p = 0.005, error
      distance: p = 0.001, total error distance: p = 0.007). It suggested that the
      proprioception feedback rather than visual feedback could be effective means to
      enhancing motor control during rehabilitation training. The developed VR system
      for rehabilitation has been verified in that stroke patients improved motor
      control after VR proprioception feedback training. 

PMID- 24110765
TI  - Kinect-based rehabilitation system for patients with traumatic brain injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death and disability
      in the age group of 0 - 44 years. Though physical exercises have proven benefits
      in the rehabilitation process, the compliance rate of patients in the home
      environment is poor. In this paper we propose a system, MotionTalk, which
      captures and analyses motion data acquired using Microsoft Kinect. It is designed
      to give a real time quantitative assessment of the exercises performed by TBI
      patients at home with respect to the same exercises performed in the clinic by
      utilizing relatively inexpensive contactless sensing and dynamic programming
      techniques. In comparison to previous reminder systems, wearable systems, and
      motion capture systems, MotionTalk is less intrusive in nature and inexpensive to
      deploy at home because it is based on readily available hardware. This was
      developed and tested on able bodied volunteers and in the future we hope to test
      it on patients with TBI, after IRB approval. 

PMID- 24110766
TI  - Estimation of physical activity monitored during the day-to-day life by an
      autonomous wearable device (SVELTE project).
AB  - Physical activity (PA) and the energy expenditure it generates (PAEE) are
      increasingly shown to have impacts on everybody's health (e.g. development of
      chronic diseases) and to be key factors in maintaining the physical autonomy of
      elderlies. The SVELTE project objective was to develop an autonomous actimeter,
      easily wearable and with several days of autonomy, which could record a subject's
      physical activity during his/her daily life and estimate the associated energy
      expenditure. A few prototypes and dedicated algorithms were developed based on
      laboratory experiments. The identification of physical activity patterns
      algorithm shows good performances (79% of correct identification), based on a
      trial in semi-free-living conditions. The assessment of the PAEE computation
      algorithm is under validation based on a clinical trial. 

PMID- 24110767
TI  - Relationship between elevated plantar pressure of toes and forefoot and gait
      features in diabetic patients.
AB  - This cross-sectional observational study is to reveal what kind of gait feature
      is relevant to elevated segment and its plantar pressure for prevention of
      diabetic foot ulcers. In 57 diabetic patients, the relationship between elevated
      plantar pressure and gait features was analyzed. To conduct this investigation, a
      simultaneous measurement system of plantar pressure and gait features was
      constructed. Plantar pressure distribution was measured by F-scan with customized
      footwear, and gait features were mainly measured using wireless motion sensors
      attached to the sacrum and feet. Several gait features of small rolling during
      the mid-stance phase were relevant to the elevated plantar pressure. 

PMID- 24110768
TI  - Evaluating the benefit of introducing medical clerks as transcriptionists to
      assist physicians in outpatient clinics: a quantitative analysis of medical
      records by counting characters.
AB  - This study evaluates the effects of the medical clerks introduced to reduce
      physicians' workloads in outpatient clinics by assisting with their documentation
      processes (e.g., the production of electronic medical records (EMRs)). The volume
      of information written in narrative text in EMRs from 2007 (pre-introduction of
      medical clerks) to 2012 (post-introduction) was measured by counting Japanese
      characters. The total number of medical records for analysis was 1,577. The
      average number of characters in EMRs increased from before the introduction of
      medical clerks to afterwards regardless of the types of documents (subjective or
      objective data) or visits (first or second visits). We conclude that introducing
      medical clerks improves the quantity of outpatients' medical records and that
      such a character-counting method is useful for evaluating the benefit of the
      introduction of medical clerks to assist physicians. 

PMID- 24110769
TI  - A smart phone/tablet based mobile health care system for developing countries.
AB  - Increasing cost of health care in developing countries is placing heavy financial
      burden on its populations. With the advent of mobile and tablet technologies
      however, it is possible to reduce this burden to some extent through tele
      healthcare. In this paper, authors describe their effort to design portable
      diagnostic devices that can communicate to smart phones and tablets there by
      making tele-healthcare possible. A possible architecture of their model is
      presented and components thereof discussed. 

PMID- 24110770
TI  - Tele-auscultation support system with mixed reality navigation.
AB  - The aim of this research is to develop an information support system for tele
      auscultation. In auscultation, a doctor requires to understand condition of
      applying a stethoscope, in addition to auscultatory sounds. The proposed system
      includes intuitive navigation system of stethoscope operation, in addition to
      conventional audio streaming system of auscultatory sounds and conventional video
      conferencing system for telecommunication. Mixed reality technology is applied
      for intuitive navigation of the stethoscope. Information, such as position,
      contact condition and breath, is overlaid on a view of the patient's chest. The
      contact condition of the stethoscope is measured by e-textile contact sensors.
      The breath is measured by a band type breath sensor. In a simulated tele
      auscultation experiment, the stethoscope with the contact sensors and the breath
      sensor were evaluated. The results show that the presentation of the contact
      condition was not understandable enough for navigating the stethoscope handling.
      The time series of the breath phases was usable for the remote doctor to
      understand the breath condition of the patient. 

PMID- 24110771
TI  - Collecting and distributing wearable sensor data: an embedded personal area
      network to local area network gateway server.
AB  - The goal of the concept and of the device presented in this contribution is to be
      able to collect sensor data from wearable sensors directly, automatically and
      wirelessly and to make them available over a wired local area network. Several
      concepts in e-health and telemedicine make use of portable and wearable sensors
      to collect movement or activity data. Usually these data are either collected via
      a wireless personal area network or using a connection to the user's smartphone.
      However, users might not carry smartphones on them while inside a residential
      building such as a nursing home or a hospital, but also within their home. Also,
      in such areas the use of other wireless communication technologies might be
      limited. The presented system is an embedded server which can be deployed in
      several rooms in order to ensure live data collection in bigger buildings. Also,
      the collection of data batches recorded out of range, as soon as a connection is
      established, is also possible. Both, the system concept and the realization are
      presented. 

PMID- 24110772
TI  - Addressing the challenges of sleep/wake class imbalance in bed based non-contact
      actigraphic recordings of sleep.
AB  - Utilising strategically positioned bed-mounted accelerometers, the Passive Sleep
      Actigraphy platform aims to deliver a non-contact method for identifying periods
      of wakefulness during night-time sleep. One of the key problems in developing
      data driven approaches for automatic sleep monitoring is managing the inherent
      sleep/wake class imbalance. In the current study, actigraphy data from three
      participants over a period of 30 days was collected. Upon examination, it was
      found that only 10% contained wake data. Consequently, this resulted in
      classifier overfitting to the majority class (sleep), thereby impeding the
      ability of the Passive Sleep Actigraphy platform to correctly identify periods of
      wakefulness during sleep; a key measure in the identification of sleep problems.
      Utilising Spread Subsample and Synthetic Minority Oversampling Techniques, this
      paper demonstrates a potential solution to this issue, reporting improvements of
      up to 28% in wake detection when compared to baseline data while maintaining an
      overall classifier accuracy of 90%. 

PMID- 24110773
TI  - Implementation of an iPhone wireless accelerometer application for the
      quantification of reflex response.
AB  - The patellar tendon reflex represents an inherent aspect of the standard
      neurological evaluation. The features of the reflex response provide initial
      perspective regarding the status of the nervous system. An iPhone wireless
      accelerometer application integrated with a potential energy impact pendulum
      attached to a reflex hammer has been successfully developed, tested, and
      evaluated for quantifying the patellar tendon reflex. The iPhone functions as a
      wireless accelerometer platform. The wide coverage range of the iPhone enables
      the quantification of reflex response samples in rural and remote settings. The
      iPhone has the capacity to transmit the reflex response acceleration waveform by
      wireless transmission through email. Automated post-processing of the
      acceleration waveform provides feature extraction of the maximum acceleration of
      the reflex response ascertained after evoking the patellar tendon reflex. The
      iPhone wireless accelerometer application demonstrated the utility of the
      smartphone as a biomedical device, while providing accurate and consistent
      quantification of the reflex response. 

PMID- 24110774
TI  - Automatically captured sociability and sleep quality in healthy adults.
AB  - Sleep and social interactions have been shown to have a considerable public
      health impact. However, little is known about how these affect each other in
      healthy individuals. This research is first to propose the exploration of the
      bidirectional relationship between technologically sensed sleep quality and
      quantified face-to-face social interactions. We detail a pilot study designed to
      study the relationship of sociability and sleep quality, both measured and
      perceived, of healthy adults. We capture real-world social interactions and
      measure sleep in a naturalistic setting using wireless sensing technologies. We
      find that it may not be the device-defined sleep quality (ZQ score) but our
      perceived sleep quality which affects our following day's sociability. Further,
      we also find perceived sleep quality is more strongly correlated to normalized ZQ
      scores than the actual scores. These intriguing insights raise several questions
      on how an individual's social life could be affected by sleep and indicate the
      usefulness of mobile sensing technologies in understanding public health
      phenomena. 

PMID- 24110775
TI  - Human activities recognition with RGB-Depth camera using HMM.
AB  - Fall detection remains today an open issue for improving elderly people security.
      It is all the more pertinent today when more and more elderly people stay longer
      and longer at home. In this paper, we propose a method to detect fall using a
      system made up of RGB-Depth cameras. The major benefit of our approach is its low
      cost and the fact that the system is easy to distribute and install. In few
      words, the method is based on the detection in real time of the center of mass of
      any mobile object or person accurately determining its position in the 3D space
      and its velocity. We demonstrate in this paper that this information is adequate
      and robust enough for labeling the activity of a person among 8 possible
      situations. An evaluation has been conducted within a real smart environment with
      26 subjects which were performing any of the eight activities (sitting, walking,
      going up, squatting, lying on a couch, falling, bending and lying down). Seven
      out of these eight activities were correctly detected among which falling which
      was detected without false positives. 

PMID- 24110776
TI  - ESUMS: a mobile system for continuous home monitoring of rehabilitation patients.
AB  - The pressure on the healthcare services is building up for several reasons. The
      ageing population trend, the increase in life-style related disease prevalence,
      as well as the increased treatment capabilities with associated general
      expectation all add pressure. The use of ambient healthcare technologies can
      alleviate the situation by enabling time and cost-efficient monitoring and follow
      up of patients discharged from hospital care. We report on an ambulatory system
      developed for monitoring of physical rehabilitation patients. The system consists
      of a wearable multisensor monitoring device; a mobile phone with client
      application aggregating the data collected; a service-oriented-architecture based
      server solution; and a PC application facilitating patient follow-up by their
      health professional carers. The system has been tested and verified for accuracy
      in controlled environment trials on healthy volunteers, and also been usability
      tested by 5 congestive heart failure patients and their nurses. This
      investigation indicated that patients were able to use the system, and that
      nurses got an improved basis for patient follow-up. 

PMID- 24110777
TI  - Fixation distance estimation using vergence eye movement for automatic focusing
      glasses.
AB  - In this study, we propose a method for estimating fixation distance on the basis
      of measurements of vergence eye movements. The aim of this approach is to control
      the lens focus of automatic focusing glasses. To reduce user effort at the time
      of calibration, the calibration was performed at infinite distance gazing, and
      the parameters were determined from the premeasured pupillary distance at
      infinity and iris diameters. To clarify the effectiveness of the proposed method,
      we conducted evaluation experiments using prototype glasses. The results showed
      that even participants requiring myopic correction could perform accurate motion
      vergence movements. Fixation distance estimation showed that, with the eye
      calibrated at infinite distance gazing, shorter distances could be estimated with
      an average accuracy exceeding 90%. 

PMID- 24110778
TI  - Potential barriers in adoption of a medication compliance neckwear by elderly
      population.
AB  - This paper presents results of a study to understand potential barriers of
      geriatric population with chronic illnesses towards adoption of a wireless
      wearable medication compliance system in the form of a neckwear. The neck being a
      critical part of the body can serve as a good source to collect a range of health
      related information on an individual. The primary research question we
      investigate here is this: for individuals with chronic illnesses especially
      amongst the elderly population how willing are they to adopt a neckwear system if
      it can monitor and mitigate health complications? Elderly patients deal with
      constant prescription changes over time and this further degrades medication
      compliance and thereby complicates an already wavering health status. A semi
      structured interview was conducted to better understand medication adherence,
      regimen and issues encountered using reminder devices with the goal of informing
      the design of a new compliance monitoring system. Results show that preserving
      health is one of the primary concerns of people living with chronic illnesses
      therefore there is a promising potential for seamless adoption of a neckwear
      medication compliance system with additional capabilities to monitor general
      health status. 

PMID- 24110779
TI  - Accuracy of caring personnel in estimating water intake based on missing liquid
      in drinking vessels.
AB  - In this contribution a measurement regarding estimations of filling levels in
      drinking vessels is presented. Ensuring a sufficient hydration is an important
      task in nursing homes. Monitoring of fluid intake is normally achieved by visual
      examination of drinking vessels conducted by staff members. This contribution
      describes a measurement targeted at evaluating this method in order to analyze
      the requirements of technical aids. Data gained by conducting this measurement in
      a cooperating elderly people home is presented and analyzed. Key results are that
      residents drink on average 5 to 10 percent less than it is recorded and that
      estimations of especially partly filled vessels vary strongly. Both, the type of
      drinking vessel and the current filling level influence the accuracy and
      precision of the difference between estimation and actual missing liquid. 

PMID- 24110780
TI  - Measurement system of body shift during Head of Bed elevation based on robust
      tracking of mattress edges using LIDAR.
AB  - This paper proposes a contactless measurement system for body shift on the
      mattress during Head of Bed (HOB) elevation to investigate detail mechanism about
      how body shift causes discomforts and pressure ulcer. For contactless
      measurement, one LIDAR captures the distance from the mattress edges to the
      shoulder, which means the upper part of body movement distance. The other LIDAR
      measures the distance to the foot, which represents that the lower part of body
      sliding. Since contours of mattress and body surface change dynamically during
      HOB elevation, the robust measurement is difficult. To overcome various changes
      of contour, a particle filter is used for robust tracking of the mattress edges
      and the foot plantar. The experiment about tracking performance and distance
      measurement demonstrated feasibility of our system in practical settings. 

PMID- 24110781
TI  - Design of an unobtrusive system for fall detection in multiple occupancy
      residences.
AB  - A small trial was conducted to examine the feasibility of detecting falls using a
      combination of ambient passive infrared (PIR) and pressure mat (PM) sensors in a
      home with multiple occupants. The key tracking method made use of graph
      theoretical concepts to track each individual in the residence and to monitor
      them independently for falls. The proposed algorithm attempts to recognize falls
      where the subject experiences a hard fall on an indoor surface that leads to loss
      of consciousness or an inability to get up from the floor without assistance, due
      to severe injuries. The sensitivity, specificity and accuracy of the algorithm in
      detecting falls are 85.00%, 80.00% and 82.86%, respectively. 

PMID- 24110782
TI  - Voice response system of color and pattern on clothes for visually handicapped
      person.
AB  - For visually handicapped people, a mental support is important in their
      independent daily life and participation in a society. It is expected to develop
      a system which can recognize colors and patterns on clothes so that they can go
      out with less concerns. We have worked on a basic study into such a system, and
      developed a prototype system which can stably recognize colors and patterns and
      immediately provide these information in voice, when a user faces it to clothes.
      In the results of evaluation experiments it is shown that the prototype system is
      superior to the system in the basic study at the accuracy rate for the
      recognition of color and pattern. 

PMID- 24110783
TI  - Work step indication with grid-pattern projection for demented senior people.
AB  - This paper proposes a work step indication method for supporting daily work with
      a grid-pattern projection. To support an independent life of demented senior
      people, it is desirable that an instruction is easy to understand visually and
      not complicated. The proposed method in this paper uses a range image sensor and
      a camera in addition to a projector. A 3D geometry of a target scene is measured
      by the range image sensor, and the grid-pattern is projected onto the scene
      directly. Direct projection of the work step is easier to be associated with the
      target objects around the assisted person, and the grid-pattern is a solution to
      indicate the spatial instruction. A prototype has been implemented and has
      demonstrated that the proposed grid-pattern projection is easy to show the work
      step. 

PMID- 24110784
TI  - An assistive technology for hearing-impaired persons: analysis, requirements and
      architecture.
AB  - In this contribution, a concept of an assistive technology for hearing-impaired
      and deaf persons is presented. The concept applies pattern recognition algorithms
      and makes use of modern communication technology to analyze the acoustic
      environment around a user, identify critical acoustic signatures and give an
      alert to the user when an event of interest happened. A detailed analysis of the
      needs of deaf and hearing-impaired people has been performed. Requirements for an
      adequate assisting device have been derived from the results of the analysis, and
      have been turned into an architecture for its implementation that will be
      presented in this article. The presented concept is the basis for an assistive
      system which is now under development at the Institute of Microsystem Engineering
      at the University of Siegen. 

PMID- 24110785
TI  - A novel non-contact radar sensor for affective and interactive analysis.
AB  - Currently, many physiological signal sensing techniques have been applied for
      affective analysis in Human-Computer Interaction applications. Most known
      maturely developed sensing methods (EEG/ECG/EMG/Temperature/BP etc. al.) replied
      on contact way to obtain desired physiological information for further data
      analysis. However, those methods might cause some inconvenient and uncomfortable
      problems, and not easy to be used for affective analysis in interactive
      performing. To improve this issue, a novel technology based on low power radar
      technology (Nanosecond Pulse Near-field Sensing, NPNS) with 300 MHz radio
      frequency was proposed to detect humans' pulse signal by the non-contact way for
      heartbeat signal extraction. In this paper, a modified nonlinear HRV calculated
      algorithm was also developed and applied on analyzing affective status using
      extracted Peak-to-Peak Interval (PPI) information from detected pulse signal. The
      proposed new affective analysis method is designed to continuously collect the
      humans' physiological signal, and validated in a preliminary experiment with
      sound, light and motion interactive performance. As a result, the mean bias
      between PPI (from NPNS) and RRI (from ECG) shows less than 1ms, and the
      correlation is over than 0.88, respectively.

PMID- 24110786
TI  - Assessment of speech production with dentures by electromagnetic articulography.
AB  - This report investigates the use of electromagnetic articulography (EMA) to
      compare basic speech patterns between a patient with traditional dentures to
      those of a normally dentate person. The goal is to assess the efficacy of
      traditional dentures in order to generate clinical data and works towards the
      improvement of denture design. Kinematic and acoustic data were acquired for
      these two subjects using a variety of repetitive vowel-consonant-vowel tasks.
      Spatiotemporal parameters indicating dynamic properties of the tongue blade and
      jaw movements, and timing coordination of the movements between them and with the
      output acoustic signal, were measured and compared within and between the
      participants. The results show significant differences in both spatial and
      temporal patterns and variation between individual tasks within each subject's
      data, as well as a difference in the two subjects' performance of the same task
      (cross-subject) for select calculated kinematic and latency parameters. It is
      concluded that there is more variation in spatiotemporal parameters in speech
      patterns for patients with dentures than without; in particular, latencies of the
      tongue blade and jaw movements and acoustic landmarks of the consonants, show
      strategies of movements timing coordination, typical of the speaker with denture.

PMID- 24110787
TI  - A micro opto-mechanical displacement sensor based on micro-diffraction gratings:
      design and characterization.
AB  - A micro opto-mechanical displacement sensor is here presented. It is constituted
      by a sensing element based on two overlapped micro-diffraction gratings (MDGs).
      They present a platinum layer (45 nm of thick) on a glass substrate, a period of
      525 um constituted by a width of 150 um of platinum separated (71.4% duty cycle).
      The working principle is based on the modulation of light intensity induced by
      the relative displacement between the MDGs: when a laser light perpendicularly
      hits the MDGs, the intensity of the transmitted light is a periodic function of
      the relative displacement between the two MDGs. A fiber optic is used to
      transport the transmitted light to a photodetector in order to avoid concerns
      related to the alignment between the optical components. The sensor's output is
      the ratio between the light intensity measured by the photodetector during the
      displacement of the MDGs and largest light intensity values measured in the whole
      range of measurement, therefore, it is lower than 1. The proposed sensor allows
      to discriminate displacement lower than 10 um, using a cost effective micro
      fabrication process implemented by the technique of Lift-Off. It shows a good
      linear behaviour in two ranges covering about one half of the MDGs period. Within
      the linear ranges it shows high sensitivity (about 0.5%/um) and good accuracy
      (lower than 4% in the whole range of calibration); furthermore, the results show
      that a design with a duty cycle of 50% overcomes the marked decrease of
      sensitivity in a range of measurement corresponding to a grating period.

PMID- 24110788
TI  - Wearable ECG recorder with acceleration sensors for monitoring daily stress:
      office work simulation study.
AB  - A small and light-weight wearable electrocardiograph (ECG) equipment with a tri
      axis accelerometer (x, y and z-axis) was developed for prolonged monitoring of
      everyday stress. It consists of an amplifier, a microcomputer with an AD
      converter, a triaxial accelerometer, and a memory card. Four parameters can be
      sampled at 1 kHz for more than 24 h and a maximum of 27 h with a default battery
      and a memory card of one giga byte (1 GB). Off-line data processing includes
      motion information along three axes and autonomic nervous system (ANS) activity
      bispectral analysis and the tone-entropy method (T-E method) from HRV data. The
      availability of the system was tested through simulated office work and three-day
      monitoring by replacing the battery and the memory card every 24 h. Both short
      term and circadian rhythms of ANS activity were clearly observed. In addition,
      sympathetic nervous activities gradually increased from the second to the third
      day. The experimental data presented verifies the functionality of the proposed
      system. 

PMID- 24110789
TI  - A high reliability detection algorithm for wireless ECG systems based on
      compressed sensing theory.
AB  - Wireless Body Area Networks (WBANs) consist of small intelligent biomedical
      wireless sensors attached on or implanted in the body to collect vital biomedical
      data from the human body providing Continuous Health Monitoring Systems (CHMS).
      The WBANs promise to be a key element in wireless electrocardiogram (ECG) systems
      for next-generation. ECG signals are widely used in health care systems as a
      noninvasive technique for diagnosis of heart conditions. However, the use of
      conventional ECG system is restricted by patient's mobility, transmission
      capacity, and physical size. Aforementioned highlights the need and advantage of
      wireless ECG systems with low sampling-rate and low power consumption. With this
      in mind, Compressed Sensing (CS) procedure as a new sampling approach and the
      collaboration from Shannon Energy Transformation (SET) and Peak Finding Schemes
      (PFS) is used to provide a robust low-complexity detection algorithm in gateways
      and access points in the hospitals and medical centers with high probability and
      enough accuracy. Advanced wireless ECG systems based on our approach will be able
      to deliver healthcare not only to patients in hospitals and medical centers; but
      also at their homes and workplaces thus offering cost saving, and improving the
      quality of life. Our simulation results show an increment of 0.1 % for
      sensitivity as well as 1.5% for the prediction level and detection accuracy. 

PMID- 24110790
TI  - NOTES suction grasper for tubular viscera--characterization of gripping force
      when varying hole size, diameter, and number.
AB  - This paper details the design and characterization of a novel suction grasper for
      Natural Orifice Transesophageal Surgery (NOTES). Axial gripping force was
      optimized by changing hole size, number, and spacing. A 10 kg pig and a rabbit
      esophagus were used to simulate a neonatal esophagus. Maximum axial forces of up
      to 7.2 N were achieved. Hole pattern spacing had little to no impact on force
      while suction area was very significant. Additionally, there was a preference for
      a greater number of holes versus larger holes for relatively large hole sizes.
      Lastly, smaller holes resulted in smoother loss of gripping force when beyond
      maximum holding force was applied. 

PMID- 24110791
TI  - Oxygen permeability measurements of contact lenses: a proposal for accuracy
      improvement.
AB  - Contact lens are a widespread medical device. In view of the importance of a
      proper oxygenation of the cornea, new materials are continuously being tested,
      with a high permeability to oxygen. Taking into account the limitations of the
      methods for testing soft contact lenses, as presented in the relevant
      international standards, this paper focuses on the polarographic method and on
      the approach of measuring oxygen permeability of stacked contact lenses. The
      effect of the interspersed saline solution layers on the measurable permeability
      of the stack is considered, using Fick's law of diffusive flux, and a proposal
      for accuracy improvement in oxygen permeability measurements is presented. 

PMID- 24110792
TI  - A syringe injection rate detector employing a dual Hall-effect sensor
      configuration.
AB  - Injection of fluids in the body using needle syringes is a standard clinical
      practice. The rate of injection can have various pathological effects on the body
      such as the pain perceived or in case of anesthesia, the amount of akinesia
      attained. Hence, a training system with a modified syringe employing a simple
      measurement scheme where a trainee can observe and practice the rate of injection
      prior to administering on actual human subjects, can be of great value towards
      reduction of complications in real life situations. In this paper, we develop a
      system for measurement of syringe injection rate with two Hall-effect sensors.
      Ring magnets attached to the body of the syringe along with the dual Hall-effect
      sensor configuration help in determining the position of the piston with respect
      to the syringe body. The two Hall-sensors are arranged in a differential
      configuration such that a linear relationship is obtained between the volume of
      liquid in the syringe (in ml) and the Hall-effect sensor output voltages. A
      prototype developed validated the measurement scheme. The rate of injection was
      displayed in real-time with a LabVIEW based Virtual Instrument. The error was
      within acceptable limits illustrating its efficacy for practical training
      purposes. 

PMID- 24110794
TI  - Monitoring of bedridden patients: development of a fall detection tool.
AB  - Falls of patients are an important issue in hospitals nowadays; it causes severe
      injuries, increases hospitalization time and treatment costs. The detection of a
      fall, in time, provides faster rescue to the patient, preventing more serious
      injuries, as well as saving nursing time. The MovinSense(r) is an electronic
      device designed for monitoring patients to prevent pressure sores, and the main
      goal of this work was to develop a new tool for this device, with the purpose of
      detecting if the patient has fallen from the hospital bed, without changing any
      of the device's original features. Experiments for gathering data samples of
      inertial signals of falling from the bed were obtained using the device. For fall
      detection a sensitivity of 72% and specificity of 100% were reached. Another
      algorithm was developed to detect if the patient got out of his/her bed. 

PMID- 24110793
TI  - Helping the blind to find the floor of destination in multistory buildings using
      a barometer.
AB  - Propelled by rapid technological advances in smart phones and other mobile
      devices, indoor navigation for the blind and visually impaired individuals has
      become an active field of research. A reliable positioning and navigation system
      will reduce suffering of these individuals, help them live more independently,
      and promote their employment. Although much progress has been made, localization
      of the floor level in a multistory building is largely an unsolved problem
      despite its high significance in helping the blind to find their ways. In this
      paper, we present a novel approach using a miniature barometer in the form of a
      low-cost MEMS chip. The relationships among the atmospheric pressure, the
      absolute height, and the floor location are described along with a real-time
      calibration method and a hardware platform design. Our experiments in a building
      of twelve floors have shown high performance of our approach. 

PMID- 24110795
TI  - Potential to fall of bipeds using foot kinematics.
AB  - This research compares normal to unexpected slipping gaits of healthy adults to
      detect potential to fall. Using various x, y, and z position analyses, including
      a Root Mean Squared Error (RMSE), significant differences are shown between
      normal and unexpected slipping gaits. Our results show that after heel strike of
      the slipping foot, the recovery foot rapidly changes position to restore balance
      and lower falling potential. We found RMSE of the recovery foot is significantly
      greater than the slipping foot, and that potential to fall is easily quantifiable
      through comparing normal to unexpected gaits. This research provides a solid
      foundations for a generalized understanding of fall potential for various gaits. 

PMID- 24110796
TI  - A pressure distribution measurement system for supporting areas of wheelchair
      users.
AB  - Pressure ulcers are skin injuries caused by long term exposition to high
      pressures on support points that interrupt blood circulation reducing the
      transport of oxygen and nutrients to the cells. They mainly affect people with
      poor mobility that stay in seating position for long periods of time. In spite of
      the diversity of commercial prototypes of cushions, ulcers caused by pressure are
      still a problem for wheelchair users. This work describes the design of a
      measurement system of pressure distribution in sedentary position. The aim of the
      system is to record the pressure concentration in order to obtain specific
      information about the supporting areas, and with these data used as feedback,
      eventually to determine an efficient random stimulation sequence to provide, in
      the future, a system to prevent these referred injuries. The proposed system
      consists of a 12 air-cell division cushion. Each cell has a pressure sensor and
      an input for electro valves to inflate and deflate. The recording and control of
      the valves is carried out through a graphical interface designed in LabVIEW(r). A
      calibration procedure for the designed cushion was made by comparing the greatest
      load values pressure with a commercial platform, similar results were obtained. 

PMID- 24110797
TI  - Medical reliable network using concatenated channel codes through GSM network.
AB  - Although the 4(th) generation (4G) of global mobile communication network, i.e.
      Long Term Evolution (LTE) coexisting with the 3(rd) generation (3G) has
      successfully started; the 2(nd) generation (2G), i.e. Global System for Mobile
      communication (GSM) still playing an important role in many developing countries.
      Without any other reliable network infrastructure, GSM can be applied for tele
      monitoring applications, where high mobility and low cost are necessary. A core
      objective of this paper is to introduce the design of a more reliable and
      dependable Medical Network Channel Code system (MNCC) through GSM Network. MNCC
      design based on simple concatenated channel code, which is cascade of an inner
      code (GSM) and an extra outer code (Convolution Code) in order to protect medical
      data more robust against channel errors than other data using the existing GSM
      network. In this paper, the MNCC system will provide Bit Error Rate (BER)
      equivalent to the BER for medical tele monitoring of physiological signals, which
      is 10(-5) or less. The performance of the MNCC has been proven and investigated
      using computer simulations under different channels condition such as, Additive
      White Gaussian Noise (AWGN), Rayleigh noise and burst noise. Generally the MNCC
      system has been providing better performance as compared to GSM.

PMID- 24110798
TI  - Lifeguard for robotic surgery assistance "LIGRA": an interactive platform
      centralizing information and control in robotic surgery.
AB  - A crying need for standardized safety management in health-care in conventional
      and in robotic surgery in particular has been identified. The same will, which
      has led to safer air transportation, can be a great source of inspiration for
      health-care. This paper proposes an interactive platform for the operating room
      with robotic surgery in view of an efficient safety implementation. 

PMID- 24110799
TI  - The diagnostic-therapeutic process. Workflow analysis and risk management with IT
      tools.
AB  - The aim of this work is to study the impact of an Information Technology (IT)
      tool on clinical risk management and Adverse Drug Events prevention in patient
      care. In this study we propose the workflow analysis and the application of
      Failure Modes Effects and Criticality Analysis (FMECA) as potential tools to
      assess the effectiveness of a specific IT tool in mitigating clinical risk. The
      study is made up of two different parts: the first one shows the decomposition
      and representation of the workflow of hospital departments using standardized
      tools from Project Management. The next phase shows the application of FMECA to
      the workflow, in order to identify critical issues and evaluate the risk
      reduction obtained using a specific IT tool, compared to the use of current
      resources. 

PMID- 24110800
TI  - Testing of Electronic Healthcare Record images and reports viewer.
AB  - Electronic Health Record (EHR) is a distributed system that results from the
      cooperation of several heterogeneous and autonomous subsystems. It improves
      health care by enabling access to prior diagnostic information to assist in
      health decisions. We focus on the image and imaging report visualization
      component that needs to interoperate with several other systems to enable
      healthcare professionals visualize a patient's imaging record. We propose and
      describe an environment that has been built and used to facilitate the
      development of the viewer component. This environment has also been used to test
      and verify the interoperability of the viewer component with other EHR components
      in accordance with the Integrating the Healthcare Enterprise (IHE) technical
      framework. It has also been used to demonstrate functionalities, to educate end
      users, and to train maintenance and test engineers. Moreover, it has been used
      for acceptance testing as part of an EHR deployment project. We also discuss the
      challenges we faced in constructing the testing data and describe the software
      developed to automatically populate the test environment with valid data. 

PMID- 24110801
TI  - Concept and approach of human signal-molecular-profiling database: a pilot study
      on depression using Lab-on-chips.
AB  - Signal molecular profiling (SMP) in serum can reveal abundant medical information
      about the human body. The construction of a human signal-molecular-profiling
      database (HSMPD) will greatly prompt the research of medical science. However,
      some challenges hinder the construction of HSMPD. A promising strategy is
      proposed to provide a convenient way for the establishment of HSMPD. Firstly, a
      low-cost and high-throughput tool for measuring SMP should be developed and
      standardized. When the SMP-oriented tools were accepted by most hospitals
      worldwide, SMP information will be decoded by a cloud-based system and stored
      into the online database naturally. In the pilot study, an ultrasensitive Lab-on
      chips (LOC) device was developed as a specific tool for SMP. Clinical serum
      samples from 10 women within 4 weeks of giving birth, including 2 patients with
      postpartum depression were studied by the LOC devices, since accumulating
      evidence has indicated that hormones and cytokines in patients with mood
      disorders are abnormal. HSMPD may be applied to diagnose depression in the
      future. Here, five kinds of signal molecules were quantified on the devices,
      namely, tumor necrosis factor-alpha (TNF-alpha), thyroid-stimulating hormone
      (TSH), interleukin (IL)-2, IL-6 and IL-8. The preliminary results showed that the
      concentrations of IL-2 and IL-8 in the depression group may be higher than those
      in the control group, whereas the other kinds of signal molecules did not change
      significantly. Although the correlations are not enough to induct any diagnostic
      criterion, the SMP-oriented tool was verified. The results also indicated that
      the strategy to establish HSMPD is conceivable. 

PMID- 24110802
TI  - Ethical concerns caused by integrative patient empowerment solutions for
      personalized medicine.
AB  - Personalized medicine that promises targeted treatments with high therapeutic
      effectiveness requires an unmatched degree of participation of the patient. To
      enable this high degree of patient empowerment, the project p-medicine developed
      a Patient Empowerment Tool that is part of a clinical research infrastructure
      consisting of data management, data warehouse, biobank access, imaging,
      simulation and decision support tools. Patient autonomy is enhanced by giving
      patients access to their data and by providing means for informed choices and
      consent. Because the highly integrative nature of the Patient Empowerment Tool
      raised ethical concerns, an ethical requirements analysis was carried out,
      resulting in the assignment of five ethical clusters. The one concerned with the
      Patient Empowerment Tool was used to identify several concerns, like the access
      to unfavorable information or negative diagnosis, incomprehensible risk/benefit
      display, and other factors that may overstress certain patients. From the ethical
      point of view, the user interface should contain different profiles and control
      mechanisms to protect the patient and to provide an adaptable and intelligent
      display of information, sufficient guidance and help for users from vulnerable
      populations as well as for patients with life threatening diseases. 

PMID- 24110803
TI  - Mapping query terms to data and schema using content based similarity search in
      clinical information systems.
AB  - This paper reports on the issues in mapping the terms of a query to the field
      names of the schema of an Entity Relationship (ER) model or to the data part of
      the Entity Attribute Value (EAV) model using similarity based Top-K algorithm in
      clinical information system together with an extension of EAV mapping for
      medication names. In addition, the details of the mapping algorithm and the
      required pre-processing including NLP (Natural Language Processing) tasks to
      prepare resources for mapping are explained. The experimental results on an
      example clinical information system demonstrate more than 84 per cent of accuracy
      in mapping. The results will be integrated into our proposed Clinical Data
      Analytics Language (CliniDAL) to automate mapping process in CliniDAL. 

PMID- 24110804
TI  - Merging medical informatics and automated diagnostic methods.
AB  - In many instances disease diagnosis is more of an art than a science due to the
      complexity of disease, lack of detailed information on parameters that are
      indicative of the disease, and lack of sufficient data to apply these parameters
      to both diagnosis and treatment. Broad-based expansion of electronic health
      records (EHRs) will produce additional data for improved model development.
      However many obstacles remain. Patient record content is not broadly available
      because of privacy concerns and the lack of standardization of EHR formats. If
      available on a large scale, de-identified medical records can provide a basis for
      development of disease models by removing privacy concerns. Once comprehensive
      disease models have been developed that assist in identifying possible diseases
      and also include parameters that were utilized along with their relative
      importance, automated analytic methods can be used to indicate the likelihood of
      the presence of specific diseases. Although the physician will always remain as
      the final expert, these methods can provide an expanded information set and
      provide analysis that is too complex for standard methods. 

PMID- 24110805
TI  - New use cases for remote control and configuration of interoperable medical
      devices.
AB  - The newest branch of the ISO/IEEE 11073 (X73) standard for Personal Health
      Devices (X73PHD), allow the development of interoperable personal health
      ecosystems. At the moment of this writing, more than 11 specializations have been
      successfully published by the Personal Health Device (PHD) Working Group (PHD
      WG). Nevertheless, some recent specializations at draft stage show the need for a
      procedure to control configuration parameters. As a solution, some ad-hoc methods
      have been elaborated to deal with it, but, the aim of the PHD WG is to
      standardize a general procedure, valid for longer term. Then it is needed to
      identify use cases requiring remote configuration services. This work identifies
      and studies new use cases that employ remote configuration services. The
      resulting use cases, discussed within the PHD WG to get the maximum consensus,
      are within the scope of the Basic Electrocardiograph (X73-10406), the Sleep Apnea
      Breathing Therapy Equipment (X73-10424), and the Medication Monitor (X73-10472)
      specializations. In addition, a classification of the findings is proposed for
      each use case. These findings could be the basis for the new remote configuration
      extension. 

PMID- 24110806
TI  - Real time biomedical signal transmission of mixed ECG signal and patient
      information using visible light communication.
AB  - The utilization of radio-frequency (RF) communication technology in healthcare
      application, especially in the transmission of health-related data such as
      biomedical signal and patient information is often perturbed by electromagnetic
      interference (EMI). This will not only significantly reduce the accuracy and
      reliability of the data transmitted, but could also compromise the safety of the
      patients due to radio frequency (RF) radiation. In this paper, we propose a
      method which utilizes visible light communication technology as a platform for
      transmission and to provide real-time monitoring of heart rate and patient
      information. White LED beam is used as the illuminating source to simultaneously
      transmit biomedical signal as well as patient record. On-off Keying (OOK)
      modulation technique is used to modulate all the data onto the visible light
      beam. Both types of data will be transmitted using a single data packet. At the
      receiving end, a receiver circuit consisting of a high-speed PIN photodetector
      and a demodulation circuit is employed to demodulate the data from the visible
      light beam. The demodulated data is then serially transmitted to a personal
      computer where the biomedical signal, patient information and heart rate can be
      monitored in real-time. 

PMID- 24110807
TI  - Using an injection signal to reduce motion artifacts in capacitive ECG
      measurements.
AB  - Capacitive electrodes are a promising alternative to the conventional adhesive
      ECG electrodes. They provide more comfort to the patient when integrated in
      everyday objects (e.g. beds or seats) for long-term monitoring. However, the
      application of such electrodes is limited by their high sensitivity to motion
      artifacts. Artifacts caused by variation of the coupling capacitance are studied
      here. An injection signal is proposed to track these variations in real-time. An
      adaptive filter then estimates the motion artifact and cancels it from the
      recorded ECG. The amplitude of the motion artifact is reduced in average by 29 dB
      in simulation and by 20 dB in a lab environment. Our method has the advantages
      that it is able to reduce motion artifacts occurring in the frequency band of the
      ECG and that it does not require knowledge about the measurement system. 

PMID- 24110808
TI  - Human pose recovery for rehabilitation using ambulatory sensors.
AB  - In this paper, an approach for lower-leg pose recovery from ambulatory sensors is
      implemented and validated in a clinical setting. Inertial measurement units are
      attached to patients undergoing physiotherapy. The sensor data is combined with a
      kinematic model within an extended Kalman filter framework to perform joint angle
      estimation. Anthropometric joint limits and process noise adaptation are employed
      to improve the quality of the joint angle estimation. The proposed approach is
      tested on 7 patients following total hip or knee joint replacement surgery. The
      proposed approach achieves an average root-mean-square error of 0.12 radians at
      key poses. 

PMID- 24110809
TI  - A novel gradient adaptive step size LMS algorithm with dual adaptive filters.
AB  - Least mean square (LMS) adaptive filter has been used to extract life signals
      from serious ambient noises and interferences in biomedical applications.
      However, a LMS adaptive filter with a fixed step size always suffers from slow
      convergence rate or large signal distortion due to the diversity of the
      application environments. An ideal adaptive filtering system should be able to
      adapt different environments and obtain the useful signals with low distortion.
      Adaptive filter with gradient adaptive step size is therefore more desirable in
      order to meet the demands of adaptation and convergence rate, which adjusts the
      step-size parameter automatically by using gradient descent technique. In this
      paper, a novel gradient adaptive step size LMS adaptive filter is presented. The
      proposed algorithm utilizes two adaptive filters to estimate gradients
      accurately, thus achieves good adaptation and performance. Though it uses two LMS
      adaptive filters, it has a low computational complexity. An active noise
      cancellation (ANC) system with two applications for extracting heartbeat and lung
      sound signals from noises is used to simulate the performance of the proposed
      algorithm. 

PMID- 24110810
TI  - Non-parametric permutation thresholding for adaptive nonlinear beamformer
      analysis on MEG revealed oscillatory neuronal dynamics in human brain.
AB  - Adaptive nonlinear beamformer technique for analyzing magnetoencephalography
      (MEG) data has been proved to be powerful tool for both brain research and
      clinical applications. A general method of analyzing multiple subject data with a
      formal statistical treatment for the group data has been developed and applied
      for various types of MEG data. Our latest application of this method was frontal
      midline theta rhythm (Fmtheta), which indicates focused attention and appears
      widely distributed over medial prefrontal areas in EEG recordings. To localize
      cortical generators of the magnetic counterpart of Fmtheta precisely and identify
      cortical sources and underlying neural activity associated with mental
      calculation processing (i.e., arithmetic subtraction), we applied adaptive
      nonlinear beamformer and permutation analysis on MEG data. As a result, it was
      indicated that Fmtheta is generated in the dorsal anterior cingulate and adjacent
      medial prefrontal cortex. Gamma event-related synchronization is as an index of
      activation in right parietal regions subserving mental subtraction associated
      with basic numerical processing and number-based spatial attention. Gamma
      desynchronization appeared in the right lateral prefrontal cortex, likely
      representing a mechanism to interrupt neural activity that can interfere with the
      ongoing cognitive task. We suggest that the combination of adaptive nonlinear
      beamformer and permutation analysis on MEG data is quite powerful tool to reveal
      the oscillatory neuronal dynamics in human brain. 

PMID- 24110811
TI  - Cortico-muscular coherence on artifact corrected EEG-EMG data recorded with a MRI
      scanner.
AB  - Simultaneous recording of electroencephalogram (EEG) and electromyogram (EMG)
      with magnetic resonance imaging (MRI) provides great potential for studying human
      brain activity with high temporal and spatial resolution. But, due to the MRI,
      the recorded signals are contaminated with artifacts. The correction of these
      artifacts is important to use these signals for further spectral analysis. The
      coherence can reveal the cortical representation of peripheral muscle signal in
      particular motor tasks, e.g. finger movements. The artifact correction of these
      signals was done by two different algorithms the Brain vision analyzer (BVA) and
      the Matlab FMRIB plug-in for EEGLAB. The Welch periodogram method was used for
      estimating the cortico-muscular coherence. Our analysis revealed coherence with a
      frequency of 5Hz in the contralateral side of the brain. The entropy is estimated
      for the calculated coherence to get the distribution of coherence in the scalp.
      The significance of the paper is to identify the optimal algorithm to rectify the
      MR artifacts and as a first step to use both these signals EEG and EMG in
      conjunction with MRI for further studies. 

PMID- 24110812
TI  - DBS artifact suppression using a time-frequency domain filter.
AB  - Electroencephalogram (EEG) is a useful tool for brain research. However, during
      Deep-Brain Stimulation (DBS), there are large artifacts that obscure the
      physiological EEG signals. In this paper, we aim at suppressing the DBS artifacts
      by means of a time-frequency-domain filter. As a pre-processing step, Empirical
      Mode Decomposition (EMD) is applied to detrend the raw data. The detrended
      signals are then filtered iteratively until, by visual inspection, the quality is
      good enough for interpretation. The proposed algorithm is demonstrated by an
      application to a clinical DBS-EEG data set in resting state and in finger-tapping
      condition. Moreover, a comparison with a Low-Pass filter (LPF) is provided, by
      visual inspection and by a quantitative measure. 

PMID- 24110813
TI  - MEG-EEG fusion by Kalman filtering within a source analysis framework.
AB  - The fusion of data from multiple neuroimaging modalities may improve the temporal
      and spatial resolution of non-invasive brain imaging. In this paper, we present a
      novel method for the fusion of simultaneously recorded electroencephalograms
      (EEG) and magnetoencephalograms (MEG) within the framework of source analysis.
      This method represents an extension of a previously published spatio-temporal
      inverse solution method to the case of MEG or combined MEG-EEG signals. Moreover,
      we use a state-of-the-art realistic finite element (FE) head model especially
      calibrated for the MEG-EEG fusion problem. Using a real data set containing an
      epileptic spike, we validate the source analysis results of the spatio-temporal
      inverse solution using the results of the LORETA method and the findings from
      other structural and functional modalities. We show that the proposed fusion
      method, despite the low signal-to-noise ratio (SNR) of single spikes, points to
      the same brain area that was found by the other modalities. Furthermore, it
      correctly identifies the same source as the main generator for the MEG and EEG
      spikes. 

PMID- 24110814
TI  - Robust sleep apnea monitoring using heart rate variability and extended Kalman
      classification based on single lead ECG.
AB  - Sleep apnea diagnosis requires analysis of long term polysomnographic signal
      during one period of night sleep. Limited access to sleep laboratories, various
      required devices and dedicated assistants made the diagnosis of sleep apnea
      underestimated and not easily accessible to the general population. In this work,
      a classification method based on modified Kalman filter which uses heart rate
      variability (HRV) wavelet signal obtained from a single electrocardiogram (ECG)
      lead is proposed. A pre-filtering was performed on wavelet transform to improve
      the correlation of extracted features. Sample entropy was used to enhance the
      convergence rate and accuracy of classification. The performance of the proposed
      method was evaluated in terms of accuracy, sensitivity and specificity. The
      classifier overcomes these methods by 5.3% to 7.2% improvements in accuracy. 

PMID- 24110815
TI  - Linear dynamic models for classification of single-trial EEG.
AB  - This paper investigates the use of linear dynamic models (LDMs) to improve
      classification of single-trial EEG signals. Existing dynamic classification of
      EEG uses discrete-state hidden Markov models (HMMs) based on piecewise-stationary
      assumption, which is inadequate for modeling the highly non-stationary dynamics
      underlying EEG. The continuous hidden states of LDMs could better describe this
      continuously changing characteristic of EEG, and thus improve the classification
      performance. We consider two examples of LDM: a simple local level model (LLM)
      and a time-varying autoregressive (TVAR) state-space model. AR parameters and
      band power are used as features. Parameter estimation of the LDMs is performed by
      using expectation-maximization (EM) algorithm. We also investigate different
      covariance modeling of Gaussian noises in LDMs for EEG classification. The
      experimental results on two-class motor-imagery classification show that both
      types of LDMs outperform the HMM baseline, with the best relative accuracy
      improvement of 14.8% by LLM with full covariance for Gaussian noises. It may due
      to that LDMs offer more flexibility in fitting the underlying dynamics of EEG. 

PMID- 24110816
TI  - Labeling colorectal NBI zoom-videoendoscope image sequences with MRF and SVM.
AB  - In this paper, we propose a sequence labeling method by using SVM posterior
      probabilities with a Markov Random Field (MRF) model for colorectal Narrow Band
      Imaging (NBI) zoom-videoendoscope. Classifying each frame of a video sequence by
      SVM classifiers independently leads to an output sequence which is unstable and
      hard to understand by endoscopists. To make it more stable and readable, we use
      an MRF model to label the sequence of posterior probabilities. In addition, we
      introduce class asymmetry for the NBI images in order to keep and enhance frames
      where there is a possibility that cancers might have been detected. Experimental
      results with NBI video sequences demonstrate that the proposed MRF model with
      class asymmetry performs much better than a model without asymmetry. 

PMID- 24110817
TI  - Development of a tool system to support endoscope.
AB  - Natural Orifice Translumenal Endoscopic Surgery (NOTES) is a type of minimally
      invasive surgery. This surgery needs working space for operating the endoscope,
      but there is no space for it in body cavity. Therefore, we have been developing a
      surgical tool system which can be inserted from the mouth and ensure space in
      body cavity. We use magnets and a tool to ensure space, like in abdominal wall
      lifting method, without use of wire. In this paper, we designed and realized a
      system which used a tool consisting of link mechanism and magnets. The link
      mechanism consists of four-bar linkage and a compression spring. It can be driven
      only by pulling wires, changing the diameter of the tool. We designed this
      surgical tool prototype, analyzed the stress and did basic experiments. 

PMID- 24110818
TI  - Supervisory system for robot assisted laser phonomicrosurgery.
AB  - This paper presents the development of a system capable of generating safety
      alarms when unexpected or unforeseen situations are detected during larynx
      phonomicrosurgery. Such system establishes relations between the application of
      laser power and changes in laryngeal tissue characteristics and appearance. As
      core component, we propose a model able to map inputs generated by the surgeon
      when controlling the laser to an estimation of tissue temperature. Situations
      where this supervision is relevant have been identified. 

PMID- 24110819
TI  - Intraoperative bowel cleansing tool in active locomotion capsule endoscopy.
AB  - Capsule endoscopy (CE) can be considered an example of "disruptive technology"
      since it represents a bright alternative to traditional diagnostic methodologies.
      If compared with traditional endoscopy, bowel cleansing procedure in CE becomes
      of greater importance, due to the impossibility to intraoperatively operate on
      unclean gastrointestinal tract areas. Considering the promising results and
      benefits obtained in the field of CE for gastrointestinal diagnosis and
      intervention, the authors approached the bowel cleansing issue with the final aim
      to propose an innovative and easy-to-use intraoperative cleansing system to be
      applied to an active locomotion softly-tethered capsule device, already developed
      by the authors. The system, that has to be intended as an additional tool for
      intraoperatively cleansing procedure of the colonic tract, is composed by a
      flexible tube with a metallic deflector attached to the distal end; it can be
      headed to the target area through the capsule operating channel. Performances of
      the colonoscopic capsule and intraoperative cleansing capabilities were
      successfully confirmed both in an in-vitro and ex-vivo experimental session. The
      innovative intraoperative cleansing system demonstrated promising results in
      terms of water injection, colonic wall cleansing procedure and subsequent water
      suction, thus guaranteeing to reduce the risk of inadequate visualization of the
      mucosa in endoscopic procedures. 

PMID- 24110820
TI  - Parallel manipulator robot assisted femoral fracture reduction on traction table.
AB  - The principle of femoral shaft fracture reduction is to restore its pre-fractured
      limb length and mechanical axis. The current documented treatment method with
      traction table reduction does not conform to the quantitative alignment and
      reduction. There is also a great amount of X-Ray radiation exposure to both
      surgeon and patient during the procedure. For this reason, we introduced an
      innovated Parallel Manipulator Robot (PMR) application: A Femoral Shaft Fracture
      Reduction with Parallel Manipulator Robot on Traction Table. With this
      application, the quantitative control on fracture reduction and alignment can be
      achieved and the radiation exposure to both surgeons and patients can be greatly
      reduced. 

PMID- 24110822
TI  - Human abdomen recognition using camera and force sensor in medical robot system
      for automatic ultrasound scan.
AB  - Physicians use ultrasound scans to obtain real-time images of internal organs,
      because such scans are safe and inexpensive. However, people in remote areas face
      difficulties to be scanned due to aging society and physician's shortage. Hence,
      it is important to develop an autonomous robotic system to perform remote
      ultrasound scans. Previously, we developed a robotic system for automatic
      ultrasound scan focusing on human's liver. In order to make it a completely
      autonomous system, we present in this paper a way to autonomously localize the
      epigastric region as the starting position for the automatic ultrasound scan. An
      image processing algorithm marks the umbilicus and mammary papillae on a digital
      photograph of the patient's abdomen. Then, we made estimation for the location of
      the epigastric region using the distances between these landmarks. A supporting
      algorithm distinguishes rib position from epigastrium using the relationship
      between force and displacement. We implemented these algorithms with the
      automatic scanning system into an apparatus: a Mitsubishi Electric's MELFA RV-1
      six axis manipulator. Tests on 14 healthy male subjects showed the apparatus
      located the epigastric region with a success rate of 94%. The results suggest
      that image recognition was effective in localizing a human body part. 

PMID- 24110823
TI  - Development and fundamental evaluation of flexible viewpoint laparoscope using a
      oblique viewing laparoscope.
AB  - We have developed a new type of laparoscope with flexible view point. This system
      can move the view without moving laparoscope itself. To achieve the wide range of
      view moving, we used a commercial 30 degrees  oblique-viewing laparoscope and
      special lens. The system control the view by rotating the oblique-viewing
      laparoscope and a sleeve which is attached to the special lens by motors
      independently. From the evaluation experiments, we confirmed the laparoscope
      which has 70 degrees  view angle could move the view +/-60 degrees . In the image
      quality evaluation experiment, degradation of the image quality was small. The
      positioning accuracy was 2.4+/-1.7 mm repeatability was 0.48 mm which lead to
      precise view control. The system achieve the safe and smooth manipulation of the
      laparoscopic view.

PMID- 24110824
TI  - Boundary condition generating large strain on breast tumor for nonlinear
      elasticity estimation.
AB  - We describe a robotic palpation system that determines whether a breast tumor is
      benign or malignant by measuring its nonlinear elasticity. Two indenters compress
      the breast from different directions to generate sufficient strain on the inner
      tumor, which simply represents clinical dynamic testing. The nonlinear elasticity
      of the inner tumor is estimated by correcting the reaction force data of the
      surrounding soft tissue. Here, we present the basic concept of our study and
      simulation results considering geometric conditions of the indenters using a
      finite element breast model. Indenters with variable width are applied to the
      breast at several contact positions in a simulation for comparison. Our results
      indicate that when the spring stiffness between the contact position of one
      indenter and the center of the tumor equals the spring stiffness between the
      contact position of the other indenter and the center of the tumor, a larger
      contact area (i.e., larger spring stiffness) provides larger strain acting on the
      inner tumor. 

PMID- 24110825
TI  - On the use of discrete steps in robot-aided flexible needle insertion.
AB  - Needle steering devices present great potential for improving the safety and
      accuracy of medical interventions with percutaneous access. Despite significant
      advances in the field, needle steerability remains an issue to be solved by the
      scientific community. In this paper, we propose the use of discrete steps in
      flexible needle insertion, inspired by the manual procedure performed by
      physicians. Conceptually, the method relies in alternating between two motions:
      grasp-push and release-retreat. For experimental evaluation, a modified gripper
      is used along with a 6DOF robotic manipulator to control needle insertion
      velocity, rotation and grasping. Preliminary results indicate that the use of
      discrete steps minimizes some negative effects, such as slippage and needle
      buckling, observed on alternative methods, while preserving their functional
      advantages. 

PMID- 24110826
TI  - Underactuated comanipulation for ultrasound breast exams.
AB  - We investigate the possibility of providing adequate task assistance using under
      actuated robots for human-robot tool co-manipulation. This novel approach
      optimizes robot-user synergy without taking into account any a priori knowledge
      of parameters depending on the user. Six different actuation modes were compared
      for a localization and scanning task. The best performance gain was achieved for
      1 degree of under-actuation. 

PMID- 24110827
TI  - A compliant parallel mechanism for needle intervention.
AB  - This paper presents a compliant mechanism for fine motion of a medical robot for
      needle intervention procedure. The concept of this mechanism is created with the
      purpose of correcting a needle axis by translating a main robot for needle
      driving when an unexpected slip happens in needle insertion. In order to specify
      the concept, a planar compliant mechanism is designed so that the mechanism has
      maximized workspace for some given design condition. A simplified mathematical
      model for the designed mechanism is derived and then a pose controller is
      designed to track a desired trajectory in a plane, which is a similar situation
      that the compliant mechanism translates a needle driving robot to correct the
      direction of a needle. The simulation result shows good tracking performance. 

PMID- 24110828
TI  - Three-dimensional kinematic analysis of active cervical spine motion by using a
      multifaceted marker device.
AB  - Assessing cervical range of motion (CROM) is an important part of the clinical
      evaluation of patients with conditions such as whiplash syndrome. This study
      aimed to develop a convenient and accurate system involving multifaceted marker
      device (MMD)-based assessment of 3-dimensional (3D) dynamic coupled CROM and
      joint angular velocity. We used an infrared optical tracking system and our newly
      developed MMD that solved problems such as marker shielding and reflection angle
      associated with the optical tracking devices and enabled sequential and accurate
      analysis of the 3D dynamic movement of the polyaxial joint and other structurally
      complicated joints. The study included 30 asymptomatic young male volunteers
      (age, 22-27 years). The MMD consisted of 5 surfaces and 5 markers and was
      attached to the participant's forehead. We measured active CROM (axial rotation,
      flexion/extension, and lateral bending) and joint angular velocity by the MMD.
      The MMD was easy to use, safe for patients and operators, could be constructed
      economically, and generated accurate data such as dynamic coupled CROM and
      angular velocity. 

PMID- 24110829
TI  - Use of an ultra-miniaturized IMU-based motion capture system for objective
      evaluation and assessment of walking skills.
AB  - The increasing age of the world population is posing new challenges to our
      society, such as how to keep this aging population healthy and active despite of
      the age. In recent years, there has been a lot of interest for gait analysis for
      rehabilitation purposes as well as for performance assessment of this aging
      population. While current systems work well, they still have several limitations.
      Cost, need for specialized personnel, need to be used in a research center, and
      sporadic measurement prevent these systems from being widely used. The authors
      propose the use of extremely miniaturized, portable measurement systems, which
      can be worn by the users during their everyday life, and can monitor their gait
      over a long timespan. This paper presents the preliminary experiments with such a
      system. 

PMID- 24110830
TI  - Biomechanical evaluation of the phases during simulated endotracheal intubation
      (ETI): pilot study on the effect of different laryngoscopes.
AB  - Endotracheal Intubation (ETI) is a common airway procedure used to connect the
      larynx and the lungs through a windpipe in patients under emergency situations.
      The process is carried out by a laryngoscope inserted into the mouth, used to
      help doctors in visualizing the glottis and inserting the tube. Currently, very
      few studies on objective evaluation of the biomechanics of the doctors during the
      procedure have been done. Additionally, these studies have been concentrated only
      on the overall performance analysis, without any segmentation, with a consequent
      loss of important information. In this paper, the authors present a preliminary
      study on a methodology to objectively evaluate and segment the biomechanical
      performance of doctors during the ETI, using surface electromyography and
      inertial measurement units. In particular, the validation has been performed by
      comparing three kinds of laryngoscopes involving an expert doctor. Finally,
      results are presented and commented. 

PMID- 24110831
TI  - Measurement of three-dimensional posture and trajectory of lower body during
      standing long jumping utilizing body-mounted sensors.
AB  - The measurement method of three-dimensional posture and flying trajectory of
      lower body during jumping motion using body-mounted wireless inertial measurement
      units (WIMU) is introduced. The WIMU is composed of three-dimensional (3D)
      accelerometer and gyroscope of two kinds with different dynamic range and one 3D
      geomagnetic sensor to adapt to quick movement. Three WIMUs are mounted under the
      chest, right thigh and right shank. Thin film pressure sensors are connected to
      the shank WIMU and are installed under right heel and tiptoe to distinguish the
      state of the body motion between grounding and jumping. Initial and final
      postures of trunk, thigh and shank at standing-still are obtained using
      gravitational acceleration and geomagnetism. The posture of body is determined
      using the 3D direction of each segment updated by the numerical integration of
      angular velocity. Flying motion is detected from pressure sensors and 3D flying
      trajectory is derived by the double integration of trunk acceleration applying
      the 3D velocity of trunk at takeoff. Standing long jump experiments are performed
      and experimental results show that the joint angle and flying trajectory agree
      with the actual motion measured by the optical motion capture system. 

PMID- 24110832
TI  - Quantitative study of knee joint surface configurations using a morpho-functional
      approach.
AB  - Several models exist in the literature to describe knee kinematics. In this paper
      we propose a morpho-functional approach based on the determination of a simulated
      kinematics of flexion/extension from a unique CT scan acquisition. We will
      compare this kinematics to the real one obtained from experiments on one cadaver.
      In parallel, we have developed quantitative tools for the assessment of the
      motion. As the computation of these tools depends on the bone morphology, they
      can describe the state of the joint, which is not classical in the literature.
      Both tools follow the evolution of the distances between two bones during motion.
      They are called the Figure of Articular Coherence and the Index of Articular
      Coherence. In order to verify the relevance of these tools, we have tested them
      to compare different surgeries of Anterior Cruciate Ligament (ACL)
      reconstruction. 

PMID- 24110833
TI  - Computation method for available response time due to tripping at minimum foot
      clearance.
AB  - Falls prevention is important for older individuals to maintain healthy
      lifestyles and is an essential challenge in sustaining the socioeconomic
      structure of many advanced nations. Tripping has been recognized as the largest
      cause of falls and accordingly, understanding tripping-induced anterior balance
      loss is necessary in reducing the overall frequency of falls among older adults.
      Hazardous anterior balance loss due to tripping can be attributed to the mid
      swing phase event, minimum foot clearance (MFC). The mechanism of tripping
      induced anterior balance loss can be described as anterior movement of the center
      of mass (CoM) passing the frontal boundary of the supporting base between the
      swing and stance toes. The first aim of the current study was to establish a
      computational method for determining available response time (ART) to anterior
      balance loss due to tripping at MFC, in other words, the time taken for CoM to
      reach the anterior boundary and therefore, the time limit for balance recovery.
      Kinematic information of CoM and both toes in addition to simulated impact force
      due to tripping at MFC were used to estimate ART. The second aim was to apply
      correlation analysis to a range of gait parameters to identify the factors
      influencing ART. ART for balance loss in the forward direction due to tripping
      was on average. 0.11s for both the dominant and non-dominant limbs' simulated
      tripping at MFC. Correlation analysis revealed five factors at MFC that prolong
      ART including: 1) greater fore-aft distance from CoM to stance toe, 2) greater
      sideway distance from CoM to swing toe, 3) longer distance from CoM to the
      frontal boundary of the supporting base, 4) slower CoM forward velocity and 5)
      slower horizontal toe velocity. The established ART computation method can be
      utilized to examine the effects of ageing and various gait tasks on the
      likelihood of tripping-induced anterior balance loss and associated falls. 

PMID- 24110834
TI  - An experimental protocol for the definition of upper limb anatomical frames on
      children using magneto-inertial sensors.
AB  - Motion capture based on magneto-inertial sensors is a technology enabling data
      collection in unstructured environments, allowing "out of the lab" motion
      analysis. This technology is a good candidate for motion analysis of children
      thanks to the reduced weight and size as well as the use of wireless
      communication that has improved its wearability and reduced its obtrusivity. A
      key issue in the application of such technology for motion analysis is its
      calibration, i.e. a process that allows mapping orientation information from each
      sensor to a physiological reference frame. To date, even if there are several
      calibration procedures available for adults, no specific calibration procedures
      have been developed for children. This work addresses this specific issue
      presenting a calibration procedure for motion capture of thorax and upper limbs
      on healthy children. Reported results suggest comparable performance with similar
      studies on adults and emphasize some critical issues, opening the way to further
      improvements. 

PMID- 24110835
TI  - Gait phase detection in able-bodied subjects and dementia patients.
AB  - Accurate detection of gait phases allows identification of specific functional
      deficits at each phase of the gait cycle for motor function assessment. This
      paper proposes a robust gait phase detection method to identify the seven gait
      phases in overground walking for normal and pathologic gaits. Four inertial
      sensors are used to obtain knee angles, tibia angles and feet angular rate
      patterns in the sagittal plane. The key events segmenting the gait cycles are
      searched using an adaptive threshold in adaptive searching intervals to make sure
      it works well for different subjects with high variation in cadence and step
      length during walking. The subjects involved in this study are categorized into
      three groups: five healthy adult subjects, two healthy elderly subjects and two
      severe dementia patients. The experimental results have shown our method can
      reliably detect all gait phases for able-bodied subjects and dementia patients
      without subject-specific calibration. 

PMID- 24110836
TI  - The effect of bone displacement operations on facial soft tissues.
AB  - A novel biomechanical model for face soft tissue (skin, mucosa, and muscles) is
      introduced to investigate the effect of mandible and chin bone displacement on
      the overall appearance of the patient's face. Nonlinear FE analysis is applied to
      the model and the results obtained are used to help surgeons to decide the amount
      of displacement required. 

PMID- 24110837
TI  - Integration of an adaptive swing control into a neuromuscular human walking
      model.
AB  - Understanding the neuromuscular control underlying human locomotion has the
      potential to deliver practical controllers for humanoid and prosthetic robots.
      However, neurocontrollers developed in forward dynamic simulations are seldom
      applied as practical controllers due to their lack of robustness and
      adaptability. A key element for robust and adaptive locomotion is swing leg
      placement. Here we integrate a previously identified robust swing leg controller
      into a full neuromuscular human walking model and demonstrate that the integrated
      model has largely improved behaviors including walking on very rough terrain (+/
      10 cm) and stair climbing (15 cm stairs). These initial results highlight the
      potential of the identified robust swing control. We plan to generalize it to a
      range of human locomotion behaviors critical in rehabilitation robotics.

PMID- 24110838
TI  - Estimating the center of mass of a free-floating body in microgravity.
AB  - This paper addresses the issue of estimating the position of the center of mass
      (CoM) of a free-floating object of unknown mass distribution in microgravity
      using a stereoscopic imaging system. The method presented here is applied to an
      object of known mass distribution for validation purposes. In the context of a
      study of 3-dimensional ballistocardiography in microgravity, and the elaboration
      of a physical model of the cardiovascular adaptation to weightlessness, the
      hypothesis that the fluid shift towards the head of astronauts induces a
      significant shift of their CoM needs to be tested. The experiments were conducted
      during the 57th parabolic flight campaign of the European Space Agency (ESA). At
      the beginning of the microgravity phase, the object was given an initial
      translational and rotational velocity. A 3D point cloud corresponding to the
      object was then generated, to which a motion-based method inspired by rigid body
      physics was applied. Through simulations, the effects of the centroid-to-CoM
      distance and the number of frames of the sequence are investigated. In
      experimental conditions, considering the important residual accelerations of the
      airplane during the microgravity phases, CoM estimation errors (16 to 76 mm) were
      consistent with simulations. Overall, our results suggest that the method has a
      good potential for its later generalization to a free-floating human body in a
      weightless environment.

PMID- 24110839
TI  - Linear parameter varying identification of ankle joint intrinsic stiffness during
      imposed walking movements.
AB  - This paper describes a novel model structure and identification method for the
      time-varying, intrinsic stiffness of human ankle joint during imposed walking
      (IW) movements. The model structure is based on the superposition of a large
      signal, linear, time-invariant (LTI) model and a small signal linear-parameter
      varying (LPV) model. The methodology is based on a two-step algorithm; the LTI
      model is first estimated using data from an unperturbed IW trial. Then, the LPV
      model is identified using data from a perturbed IW trial with the output
      predictions of the LTI model removed from the measured torque. Experimental
      results demonstrate that the method accurately tracks the continuous-time
      variation of normal ankle intrinsic stiffness when the joint position changes
      during the IW movement. Intrinsic stiffness gain decreases from full
      plantarflexion to near the mid-point of plantarflexion and then increases
      substantially as the ankle is dosriflexed. 

PMID- 24110840
TI  - A novel algorithm for linear parameter varying identification of Hammerstein
      systems with time-varying nonlinearities.
AB  - This paper describes a novel method for the identification of Hammerstein systems
      with time-varying (TV) static nonlinearities and time invariant (TI) linear
      elements. This paper develops a linear parameter varying (LPV) state-space
      representation for such systems and presents a subspace identification technique
      that gives individual estimates of the Hammerstein components. The identification
      method is validated using simulated data of a TV model of ankle joint reflex
      stiffness where the threshold and gain of the model change as nonlinear functions
      of an exogenous signal. Pilot experiment of TV reflex EMG response identification
      in normal ankle joint during an imposed walking task demonstrate systematic
      changes in the reflex nonlinearity with the trajectory of joint position. 

PMID- 24110842
TI  - Viscoelastic interaction between intraocular microrobots and vitreous humor: a
      finite element approach.
AB  - Vitreous humor exhibits complex biomechanical properties and determination of
      these properties is essential for designing ophthalmic biomedical microdevices.
      In this paper, the viscoelastic properties of porcine vitreous humor were studied
      based on ex vivo creep experiments, in which a microrobot was magnetically
      actuated inside the vitreous. A three-dimensional (3D) finite element (FE) model
      was proposed to simulate the viscoelastic interaction between the microrobot and
      porcine vitreous humor. An optimization-based method was employed to estimate the
      viscoelastic parameters of the vitreous humor. The proposed model successfully
      validated the experimental measurements. The estimated parameters were compared
      with published data in literature. The model was then used to study the shape
      dependent interaction of the microrobot with the vitreous humor. The methods
      presented in this paper can be used for the optimization of ophthalmic
      microrobots and microsurgical tools. 

PMID- 24110841
TI  - Using CamiTK for rapid prototyping of interactive computer assisted medical
      intervention applications.
AB  - Computer Assisted Medical Intervention (CAMI hereafter) is a complex multi
      disciplinary field. CAMI research requires the collaboration of experts in
      several fields as diverse as medicine, computer science, mathematics,
      instrumentation, signal processing, mechanics, modeling, automatics, optics, etc.
      CamiTK is a modular framework that helps researchers and clinicians to
      collaborate together in order to prototype CAMI applications by regrouping the
      knowledge and expertise from each discipline. It is an open-source, cross
      platform generic and modular tool written in C++ which can handle medical images,
      surgical navigation, biomedicals simulations and robot control. This paper
      presents the Computer Assisted Medical Intervention ToolKit (CamiTK) and how it
      is used in various applications in our research team.

PMID- 24110843
TI  - Synchronous simulation for deformation of liver and gallbladder with stretch and
      compression compensation.
AB  - One challenge in surgical simulation is to design stable deformable models to
      simulate the dynamics of organs synchronously. In this paper, we develop a novel
      mass-spring model on the tetrahedral meshes for soft organs such as the liver and
      gallbladder, which can stably deform with large time steps. We model the contact
      forces between the organs as a kind of forces generated by the tensions of
      repulsive springs connecting in between the organs. The simulation system couples
      a pair of constraints on the length of springs with an implicit integration
      method. Based on the novel constraints, our simulator can efficiently preserve
      the volumes and geometric properties of the liver and gallbladder during the
      simulation. The numerical examples demonstrate that the proposed simulation
      system can provide realistic and stable deformable results. 

PMID- 24110844
TI  - Image plane positioning by pneumatic actuators for ultrasound guidance.
AB  - Image guided procedures such as percutaneous needle insertion or high intensity
      focused ultrasound, have become quite widespread. In images acquisition,
      ultrasound (US) is convenient to use in a conventional operating room, and
      inexpensive compared to CT and MRI. However, US requires to handle an US probe
      and do not have the base coordinate system. Therefore, intraoperative image
      position is unclear and cannot position to interested area. To address the
      issues, we have developed a robotic system based on US calibration and a probe
      scanning robot. In this study, to validate the implement system, positioning
      accuracy of an image plane was evaluated. Moreover, we developed an automated US
      guidance system with a conventional US probe. The system enables image plane
      positioning to visualize a therapeutic tool automatically. From the results,
      positioning accuracy of the image plane was 1.6 mm and 1.5 deg, maximally. In the
      phantom test, the error between the positions of the image plane and the mock
      needle was 2.5 mm and 0.9 deg. We have confirmed that the proposed system is
      greatly applicable for an intraoperative US guidance. 

PMID- 24110845
TI  - An algorithm for planning the number and the pose of the iceballs in
      cryoablation.
AB  - We present an algorithm that computes the number and the pose (position and
      orientation) of iceballs in a cryoablation procedure, in order to completely
      cover the target region, i.e. the tumor. Constraints to needle insertion, such as
      regions that have to be avoided, are taken into account and satisfied. We
      developed a tool for cryosurgery planning in MATLAB and perform several
      simulations to extract information on the algorithm behavior and to verify that
      it always brings to a complete coverage. 

PMID- 24110846
TI  - Sensing elasticity from the phase difference of the stepper motor.
AB  - We have developed a made-to-order surgical support manipulator with a function
      that senses the mechanical characteristics of internal organs, and which can be
      customized based on the maximum grasping force of the patient. The purpose of
      this study is to establish an elasticity-sensing model that uses the phase
      difference of the stepper motor based on material strength and to apply it to in
      vitro organs. In this study, we propose a measurement model and develop a
      prototype that is used in experiments on silicon rubber and in vitro organs in a
      dog. Young's modulus E and spring constant K are measured by the prototype and a
      material testing machine. The results of the prototype showed good agreement with
      those of the material testing machine, and that the proposed model will be a
      great help in the development of surgical support manipulators. 

PMID- 24110847
TI  - Decoding movement intent of patient with multiple sclerosis for the powered lower
      extremity exoskeleton.
AB  - This study aims to recognize movement intent of patients with multiple sclerosis
      (MS) by decoding neuromuscular control signals fused with mechanical measurements
      as a method of powered lower extremity exoskeleton control. Surface
      electromyographic (EMG) signals recorded from the lower extremity muscles, ground
      reaction forces measured from beneath both feet, and kinematics from both thigh
      segments of a single MS patient were used to identify three activities (level
      ground walking, sitting, and standing). Our study showed that during activity
      performance clear modulation of muscle activity in the lower extremities was
      observed for the MS patient, whose Kurtzke Expanded Disability Status Scale
      (EDSS) was 6. The designed intent recognition algorithm can accurately classify
      the subject's intended movements with 98.73% accuracy in static states and
      correctly predict the activity transitions about 100 to 130 ms before the actual
      transitions were made. These promising results indicate the potential of designed
      intent recognition interface for volitional control of powered lower extremity
      exoskeletons. 

PMID- 24110848
TI  - Two-channel surface electromyography for individual and combined finger
      movements.
AB  - This paper proposes the pattern recognition system for individual and combined
      finger movements by using two channel electromyography (EMG) signals. The
      proposed system employs Spectral Regression Discriminant Analysis (SRDA) for
      dimensionality reduction, Extreme Learning Machine (ELM) for classification and
      the majority vote for the classification smoothness. The advantage of the SRDA is
      its speed which is faster than original LDA so that it could deal with multiple
      features. In addition, the use of ELM which is fast and has similar
      classification performance to well-known SVM empowers the classification system.
      The experimental results show that the proposed system was able to recognize the
      individual and combined fingers movements with up to 98 % classification accuracy
      by using only just two EMG channels.

PMID- 24110849
TI  - Comparison of complexity of EMG signals between a normal subject and a patient
      after stroke--a case study.
AB  - An innovative method to quantitatively assess the motor function of upper
      extremities for post-stroke patients is proposed. A post-stroke patient and a
      normal subject were recruited to conduct a special performance of voluntary elbow
      flexion and extension by following a sinusoidal trajectory from 30 degrees  to 90
      degrees  at 6 different peak angular velocities in a horizontal plane. During the
      test, the elbow angle and subject's electromyographic (EMG) signal (biceps
      brachii and triceps brachii) were recorded simultaneously. Fuzzy approximate
      entropy (fApEn) was applied to analyze the EMG signals. The results showed
      observable differences in fApEn when the control and the patient (unaffected and
      affected arms) were compared, and an uptrend of fApEn was detected with the
      increase in the tracking velocities in both the normal individual and patient
      (unaffected and affected arm). The fApEn values, which are a measure of
      complexity of EMG, could be used for the quantitative evaluation of the
      deficiencies of motor control induced by stroke. 

PMID- 24110850
TI  - The role of proprioceptive feedback in Parkinsonian resting tremor.
AB  - In this paper we use a closed-loop force feedback system to investigate the
      effect of altering proprioceptive feedback on EEG and resting tremor in
      Parkinson's Disease. A velocity dependent counterforce simulating viscous
      friction was provided by haptic robots with simultaneous recording of kinematics,
      EMG and EEG while a patient was on and off dopaminergic medication' We were able
      to reduce the amplitude of the tremor. We also showed that force feedback shifts
      the center of EEG-EMG coherence posteriorly toward the somatosensory regions,
      which may have ramifications for noninvasive therapies. 

PMID- 24110851
TI  - Linear model of peripheral nerve after surgical manipulation: preliminary report
      in animal study and model shift.
AB  - Generally, the neurophysiologic intra-operative monitoring (NIOM) is acknowledged
      to correlate with reducing the risk of perioperative neurological deficits. This
      electrophysiological method is commonly used and neurosurgeons could aware where
      the nervous system is at risk of being permanently injured while doing the
      operation under NIOM. However, this monitoring is quite a qualitative evaluation.
      Neurosurgeons have to use their own experiences to consider and made the
      estimation. Traditionally, the peripheral nerve function can be preserved by
      continuous electromyography (EMG) and compound muscle action potential response
      (CMAP) monitoring. The spike and burst EMG occur when the nerve trunk is
      irritated or damaged. Decreased amplitude of CMAP response is also considered as
      nerve damage even it might cause from a severe irritation. By using this
      information, the peripheral nerve function is qualitatively evaluated by the
      surgeons. This present study proposed a new predictive nerve model for peripheral
      nerve function prediction. This input and output data were used for nerve
      modeling in each condition. The results showed that parameters of the linear
      nerve model had significantly differences and tendency changes in each nerve
      condition. Therefore, the proposed method for predicting the nerve function by
      the shifted linearly nerve model might be a promising approach for peripheral
      nerve function estimation in the human nerve model. 

PMID- 24110852
TI  - Wireless-based portable EEG-EOG monitoring for real time drowsiness detection.
AB  - Drowsiness is one of the major risk factors causing accidents that result in a
      large number of damage. Drivers and industrial workers probably have a large
      effect on several mishaps occurring from drowsiness. Therefore, advanced
      technology to reduce these accidental rates is a very challenging problem.
      Nowadays, there have been many drowsiness detectors using electroencephalogram
      (EEG), however, the cost is still high and the use of this is uncomfortable in
      long-term monitoring because most of them require wiring and conventional wet
      electrodes. The purpose of this paper is to develop a portable wireless device
      that can automatically detect the drowsiness in real time by using the EEG and
      electrooculogram (EOG). The silver (Ag) conducting fabric consolidated in a
      headband used as dry electrodes can acquire signal from the user's forehead. The
      signal was sent via the wireless communication of XBee(r) 802.15.4 to a
      standalone microcontroller to analyze drowsiness using the proposed algorithm.
      The alarm will ring when the drowsiness occurs. Besides, the automatic drowsiness
      detection and alarm device yields the real-time detection accuracy of
      approximately 81%. 

PMID- 24110853
TI  - Estimating mood variation from MPF of EMG during walking.
AB  - The information on the mood included in behavior is classified into nonverbal
      information, and is included in behavior without necessarily being based on the
      intention of an agent. Consequently, it is considered that we can estimate the
      mood from the measurement of the behavior. In this work, we estimate the mood
      from the surface electromyogram (EMG) information of the muscles of the upper
      limb during walking. Identification of emotion and mood using EMG information has
      been done with a variety of methods until now. In addition, it is known that
      human walking includes information that is specific to the individual and be
      affected by mood. Therefore, it is thought that the EMG analysis of walking is
      effective in the identification of human mood. In this work, we made a subject
      walk in the various mood states and answer psychological tests that measure the
      mood. We use two types of tasks (music listening and numerical calculation) for
      evoking different moods. Statistical features of EMG signals are calculated using
      Fast Fourier Transform (FFT) and Principal Component Analysis (PCA). These
      statistical features are related with psychological test scores, using regression
      analysis. In this paper, we have shown the statistical significance of the linear
      model to predict the variation of mood based on the information on the variation
      in MPF of EMG data of the muscles of the upper limb during walking with different
      moods. This shows the validity of such a mapping. However, since the
      interpretability of the model is still low, it cannot be said that the model is
      able to accurately represent the mood variation. Creating a model with high
      accuracy is a key issue in the future. 

PMID- 24110854
TI  - Emergence of motor synergy in vertical reaching task via tacit learning.
AB  - The dynamics of multijoint limbs often causes complex dynamic interaction torques
      which are the inertial effect of other joints motion. It is known that Cerebellum
      takes important role in a motor learning by developing the internal model. In
      this paper, we propose a novel computational control paradigm in vertical
      reaching task which involves the management of interaction torques and
      gravitational effect. The obtained results demonstrate that the proposed method
      is valid for acquiring motor synergy in the system with actuation redundancy and
      resulted in the energy efficient solutions. It is highlighted that the tacit
      learning in vertical reaching task can bring computational adaptability and
      optimality with model-free and cost-function-free approach differently from
      previous studies. 

PMID- 24110855
TI  - Effects of whole body vibration on spinal proprioception in normal individuals.
AB  - Low back pain (LBP) is a common health problem with high reoccurrence rate. While
      most LBP cases are classified as non-specific, patients in general often present
      impaired proprioception. Whole body vibration (WBV) has been proven to improve
      muscle function and proprioception in the lumbo-pelvic region. The aim of this
      study was to determine whether WBV would affect spinal proprioception. Eleven
      young normal individuals were recruited. Their body alignment, lumbar
      repositioning error and lumbo-pelvic coordination during dynamic motion were
      assessed before and after 5 minutes WBV (18 Hz, 6 mm amplitude). Assessments were
      conducted before, immediately after, 30 minutes after and 1 hour after WBV.
      Subjects were found to have improved lumbo-pelvic coordination and flexibility
      without any adverse effect on the neuromuscular system after WBV. However, WBV
      had no significant immediate effect on lumbar repositioning ability and body
      alignment. Future studies of the effects of different WBV protocols on LBP
      patients are recommended.

PMID- 24110856
TI  - A customizable stochastic state point process filter (SSPPF) for neural spiking
      activity.
AB  - Stochastic State Point Process Filter (SSPPF) is effective for adaptive signal
      processing. In particular, it has been successfully applied to neural signal
      coding/decoding in recent years. Recent work has proven its efficiency in non
      parametric coefficients tracking in modeling of mammal nervous system. However,
      existing SSPPF has only been realized in commercial software platforms which
      limit their computational capability. In this paper, the first hardware
      architecture of SSPPF has been designed and successfully implemented on field
      programmable gate array (FPGA), proving a more efficient means for coefficient
      tracking in a well-established generalized Laguerre-Volterra model for mammalian
      hippocampal spiking activity research. By exploring the intrinsic parallelism of
      the FPGA, the proposed architecture is able to process matrices or vectors with
      random size, and is efficiently scalable. Experimental result shows its superior
      performance comparing to the software implementation, while maintaining the
      numerical precision. This architecture can also be potentially utilized in the
      future hippocampal cognitive neural prosthesis design. 

PMID- 24110857
TI  - Dynamical system design for silicon neurons using phase reduction approach.
AB  - In the present paper, we apply a computer-aided phase reduction approach to
      dynamical system design for silicon neurons (SiNs). Firstly, we briefly review
      the dynamical system design for SiNs. Secondly, we summarize the phase response
      properties of circuit models of previous SiNs to clarify design criteria in our
      approach. From a viewpoint of the phase reduction theory, as a case study, we
      show how to tune circuit parameters of the resonate-and-fire neuron (RFN) circuit
      as a hybrid type SiN. Finally, we demonstrate delay-induced synchronization in a
      silicon spiking neural network that consists of the RFN circuits. 

PMID- 24110858
TI  - Electrical Morris-Lecar neuron.
AB  - In this study, an experimental electronic neuron based on Morris-Lecar model is
      presented, able to become an experimental unit tool to study collective
      association of robust coupled neurons. The circuit design is given according to
      the ionic currents of this model. The experimental results are compared to the
      theoretical prediction, leading to validate this circuit. 

PMID- 24110859
TI  - Analysis of muscle coupling during isokinetic endurance contractions by means of
      nonlinear prediction.
AB  - Isokinetic exercises have been extensively used in order to analyze muscle
      imbalances and changes associated with fatigue. It is known that such changes are
      difficult to assess from EMG signals during dynamic contractions, especially,
      using linear signal processing tools. The aim of this work was to use nonlinear
      prediction in order to analyze muscle couplings and interactions in this context
      and to assess the load-sharing of different muscles during fatigue. Results show
      promising for detecting interaction strategies between muscles and even for the
      interaction between muscles and the output torque during endurance tests. 

PMID- 24110860
TI  - Static ankle-foot orthosis improves static balance and gait functions in
      hemiplegic patients after stroke.
AB  - The purpose was to examine the effects of static anterior and posterior ankle
      foot orthoses (AAFOs & PAFOs) using with regular shoes on improving static and
      gait function in patients recovering from stroke. Static and dynamic balance
      control were measured under four conditions: barefeet, wearing regular shoes
      only, and wearing regular shoes with AAFOs or PAFOs. The results indicated that
      wearing regular shoes markedly increased the center of pressure (CoP) sway (p <
      0.05) in static standing conditions. Both AAFOs and PAFOs decreased CoP sway and
      increased bilateral limb loading symmetry compared to barefoot and wearing shoes
      alone (p < 0.05). PAFOs decreased CoP sway more than AAFOs (p > 0.05) and also
      boosted medial-lateral weight shifting more effectively (p < 0.05). Both types of
      AFOs increased walking efficiency but influenced the roll-over shape of the CoP
      adversely during level walking. The conclusions are that both AAFOs and PAFOs
      improved static and dynamic balance control when they were used with regular
      shoes and PAFOs appeared to be more efficient than AAFOs. Shoes worn daily with
      AFOs is a key consideration influencing balance control in stroke patients.
      However, AFOs with static design impeded the function of the three rocker systems
      of the foot during ambulation. 

PMID- 24110861
TI  - Detection of apnoea from respiratory time series data using clinically
      recognizable features and kNN classification.
AB  - Apnoea is a sleep related breathing disorder that is common in adults and can be
      described as a temporary closure in the upper airway during sleep. A system using
      time series analysis of one minute epochs of respiratory impedance signals to
      detect apnoea is described. An algorithm has been developed using MATLAB for
      extracting clinically recognizable features from the respiratory impedance
      signal. One minute samples are classified using kNN classification of the feature
      set. The output of the system has been shown to detect apnoeic episodes in eight
      eight-hour patient records collected from the PhysioNet database. The specificity
      of the classifier is 88.1% and the sensitivity is 95.7%. ROC analysis was
      performed and the area under the ROC curve is 0.9604. Future research will
      include testing the classifier in a much larger dataset and also a novel method
      for the presentation of classification results to physicians. 

PMID- 24110862
TI  - Respiration amplitude analysis for REM and NREM sleep classification.
AB  - In previous work, single-night polysomnography recordings (PSG) of respiratory
      effort and electrocardiogram (ECG) signals combined with actigraphy were used to
      classify sleep and wake states. In this study, we aim at classifying rapid-eye
      movement (REM) and non-REM (NREM) sleep states. Besides the existing features
      used for sleep and wake classification, we propose a set of new features based on
      respiration amplitude. This choice is motivated by the observation that the
      breathing pattern has a more regular amplitude during NREM sleep than during REM
      sleep. Experiments were conducted with a data set of 14 healthy subjects using a
      linear discriminant (LD) classifier. Leave-one-subject-out cross-validations show
      that adding the new features into the existing feature set results in an increase
      in Cohen's Kappa coefficient to a value of kappa = 0.59 (overall accuracy of
      87.6%) compared to that obtained without using these features (kappa of 0.54 and
      overall accuracy of 86.4%). In addition, we compared the results to those
      reported in some other studies with different features and signal modalities. 

PMID- 24110863
TI  - Assessment of spectral bands of interest in airflow signal to assist in sleep
      apnea-hypopnea syndrome diagnosis.
AB  - In this work, we analyze power spectral density (PSD) from single-channel airflow
      (AF) in the context of sleep apnea-hypopnea syndrome (SAHS) diagnosis. PSDs from
      SAHS-positive and SAHS-negative subjects were compared through Mann-Whitney test
      to find bands of interest. Thereby, we characterized three spectral bands (BW1
      BW3) by their relative power (P(R1)-P(R3)) and established relationships with
      apneas and hypopneas. Then, the single and joint diagnostic ability of P(R1)
      P(R3) was assessed by means of K-nearest neighbours (KNN), Fisher's linear
      discriminant (FLD), and logistic regression (LR) classifiers. The KNN and LR
      models, obtained from P(R1)-P(R3), showed the best diagnostic ability after a
      leave-one-out cross-validation procedure. 87.7%-84.2% accuracy and 0.799-0.853
      area under receiver operating characteristics curve (AROC) were achieved,
      respectively. Our results suggest that the bands of interest we defined are
      related to apneas and hypopneas and, therefore, can be useful in SAHS diagnosis.

PMID- 24110864
TI  - Metric learning for automatic sleep stage classification.
AB  - We introduce in this paper a metric learning approach for automatic sleep stage
      classification based on single-channel EEG data. We show that learning a global
      metric from training data instead of using the default Euclidean metric, the k
      nearest neighbor classification rule outperforms state-of-the-art methods on
      Sleep-EDF dataset with various classification settings. The overall accuracy for
      Awake/Sleep and 4-class classification setting are 98.32% and 94.49%
      respectively. Furthermore, the superior accuracy is achieved by performing
      classification on a low-dimensional feature space derived from time and frequency
      domains and without the need for artifact removal as a preprocessing step.

PMID- 24110865
TI  - Sleep apnea classification using least-squares support vector machines on single
      lead ECG.
AB  - In this paper a methodology to identify sleep apnea events is presented. It uses
      four easily computable features, three generally known ones and a newly proposed
      feature. Of the three well known parameters, two are computed from the RR
      interval time series and the other one from the approximate respiratory signal
      derived from the ECG using principal component analysis (PCA). The fourth feature
      is proposed in this paper and it is computed from the principal components of the
      QRS complexes. Together with a least squares support vector machines (LS-SVM)
      classifier using an RBF kernel, these four features achieve an accuracy on test
      data larger than 85% for a subject independent classification, and of more than
      90% for a patient specific approach. These values are comparable with other
      results in the literature, but have the advantage that their computation is
      straightforward and much simpler. This can be important when implemented in a
      home monitoring system, which typically has limited computational resources. 

PMID- 24110866
TI  - Decision tree for smart feature extraction from sleep HR in bipolar patients.
AB  - The aim of this work is the creation of a completely automatic method for the
      extraction of informative parameters from peripheral signals recorded through a
      sensorized T-shirt. The acquired data belong to patients affected from bipolar
      disorder, and consist of RR series, body movements and activity type. The
      extracted features, i.e. linear and non-linear HRV parameters in the time domain,
      HRV parameters in the frequency domain, and parameters indicative of the sleep
      quality, profile and fragmentation, are of interest for the automatic
      classification of the clinical mood state. The analysis of this dataset, which is
      to be performed online and automatically, must address the problems related to
      the clinical protocol, which also includes a segment of recording in which the
      patient is awake, and to the nature of the device, which can be sensitive to
      movements and misplacement. Thus, the decision tree implemented in this study
      performs the detection and isolation of the sleep period, the elimination of
      corrupted recording segments and the checking of the minimum requirements of the
      signals for every parameter to be calculated. 

PMID- 24110867
TI  - Compression based entropy estimation of heart rate variability on multiple time
      scales.
AB  - Heart rate fluctuates beat by beat in a complex manner. The aim of this study was
      to develop a framework for entropy assessment of heart rate fluctuations on
      multiple time scales. We employed the Lempel-Ziv algorithm for lossless data
      compression to investigate the compressibility of RR interval time series on
      different time scales, using a coarse-graining procedure. We estimated the
      entropy of RR interval time series of 20 young and 20 old subjects and also
      investigated the compressibility of randomly shuffled surrogate RR time series.
      The original RR time series displayed significantly smaller compression entropy
      values than randomized RR interval data. The RR interval time series of older
      subjects showed significantly different entropy characteristics over multiple
      time scales than those of younger subjects. In conclusion, data compression may
      be useful approach for multiscale entropy assessment of heart rate variability. 

PMID- 24110868
TI  - Different approaches of symbolic dynamics to quantify heart rate complexity.
AB  - The analysis of symbolic dynamics applied to physiological time series is able to
      retrieve information about dynamical properties of the underlying system that
      cannot be gained with standard methods like e.g. spectral analysis. Different
      approaches for the transformation of the original time series to the symbolic
      time series have been proposed. Yet the differences between the approaches are
      unknown. In this study three different transformation methods are investigated:
      (1) symbolization according to the deviation from the average time series, (2)
      symbolization according to several equidistant levels between the minimum and
      maximum of the time series, (3) binary symbolization of the first derivative of
      the time series. Each method was applied to the cardiac interbeat interval series
      RR(i) and its difference DeltaRR(I) of 17 healthy subjects obtained during head
      up tilt testing. The symbolic dynamics of each method is analyzed by means of the
      occurrence of short sequences ('words') of length 3. The occurrence of words is
      grouped according to words without variations of the symbols (0V%), words with
      one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%).
      Linear regression analysis showed that for method 1 0V%, 1V%, 2LV% and 2UV%
      changed with increasing tilt angle. For method 2 0V%, 2LV% and 2UV% changed with
      increasing tilt angle and method 3 showed changes for 0V% and 1V%. In conclusion,
      all methods are capable of reflecting changes of the cardiac autonomic nervous
      system during head-up tilt. All methods show that even the analysis of very short
      symbolic sequences is capable of tracking changes of the cardiac autonomic
      regulation during head-up tilt testing.

PMID- 24110869
TI  - Entropy-based complexity of the cardiovascular control in Parkinson disease:
      comparison between binning and k-nearest-neighbor approaches.
AB  - Entropy-based approaches are frequently used to quantify complexity of short-term
      cardiovascular control from spontaneous beat-to-beat variability of heart period
      (HP) and systolic arterial pressure (SAP). Among these tools the ones optimizing
      a critical parameter such as the pattern length are receiving more and more
      attention. This study compares two entropy-based techniques for the
      quantification of complexity making use of completely different strategies to
      optimize the pattern length. Comparison was carried out over HP and SAP
      variability series recorded from 12 Parkinson's disease (PD) patients without
      orthostatic hypotension or symptoms of orthostatic intolerance and 12 age-matched
      healthy control (HC) subjects. Regardless of the method, complexity of
      cardiovascular control increased in PD group, thus suggesting the early
      impairment of cardiovascular function. 

PMID- 24110870
TI  - Decomposing the transfer entropy to quantify lag-specific Granger causality in
      cardiovascular variability.
AB  - We present a modification of the well known transfer entropy (TE) which makes it
      able to detect, besides the direction and strength of the information transfer
      between coupled processes, its exact timing. The approach follows a decomposition
      strategy which identifies--according to a lag-specific formulation of the concept
      of Granger causality--the set of time delays carrying significant information,
      and then assigns to each of these delays an amount of information transfer such
      that the total contribution yields the overall TE. We propose also a procedure
      for the practical estimation from time series data of the relevant delays and lag
      specific TE in both bivariate and multivariate settings. The proposed approach is
      tested in simulations and in real cardiovascular time series, showing the
      feasibility of lag-specific TE estimation, the ability to reflect expected
      mechanisms of cardiovascular regulation, and the necessity of using the
      multivariate TE to properly assess time-lagged information transfer in the
      presence of multiple interacting systems.

PMID- 24110871
TI  - Assessing sample entropy of physiological signals by the norm component matrix
      algorithm: application on muscular signals during isometric contraction.
AB  - Sample Entropy (SampEn) is a popular method for assessing the unpredictability of
      biological signals. Its calculation requires to preliminarily set the tolerance
      threshold r and the embedding dimension m. Even if most studies select m=2 and
      r=0.2 times the signal standard deviation, this choice is somewhat arbitrary.
      Effects of different r and m values on SampEn have been rarely assessed, because
      of the high computational burden of this task. Recently, however, a fast
      algorithm for estimating correlation sums (Norm Component Matrix, NCM) has been
      proposed that allows calculating SampEn quickly over wide ranges of r and m. The
      aim of our work is to describe the structure of SampEn of physiological signals
      with different complex dynamics as a function of m and r and in relation to the
      correlation sum. In particular, we investigate whether the criterion of "maximum
      entropy" for selecting r previously proposed for Approximate Entropy, also
      applies to SampEn; and whether information from correlation sums provides
      indications for the choice of r and m. For this aim we applied the NCM algorithm
      on electromyographic and mechanomyographic signals during isometric muscle
      contraction, estimating SampEn over wide ranges of r (0.01 <= r <= 5) and m (from
      1 to 11). Results indicate that the "maximum entropy" criterion to select r in
      Approximate Entropy cannot be applied to SampEn. However, the analysis of
      correlation sums alternatively suggests to choose r that at any m maximizes the
      number of "escaping vectors", i.e., data points effectively contributing to the
      SampEn estimation.

PMID- 24110872
TI  - Entropy analysis of MEG background activity in attention-deficit/hyperactivity
      disorder.
AB  - The aim of this study was to analyze the magnetoencephalography (MEG) background
      activity in Attention-Deficit/Hyperactivity Disorder (ADHD) using fuzzy entropy
      (FuzzyEn), an entropy measure that quantifies signal irregularity. Five minutes
      of recording were acquired with a 148-channel whole-head magnetometer in 14 ADHD
      patients and 14 control children. Our results showed that MEG activity was more
      regular in ADHD patients than in controls. Additionally, there were statistically
      significant differences (p < 0.01, Student's t-test with Bonferroni's correction)
      in the five analyzed brain regions: anterior, central, posterior, left lateral,
      and right lateral. Using receiver operating characteristic (ROC) curves, the
      highest values of accuracy (82.14%) and area under the ROC curve (0.9005) were
      achieved in anterior area. Our results support the hypothesis that ADHD is
      characterized by a delay of cortical maturation in the prefrontal cortex. 

PMID- 24110873
TI  - Approximation-based common principal component for feature extraction in multi
      class brain-computer interfaces.
AB  - Common Spatial Pattern (CSP) is a state-of-the-art method for feature extraction
      in Brain-Computer Interface (BCI) systems. However it is designed for 2-class BCI
      classification problems. Current extensions of this method to multiple classes
      based on subspace union and covariance matrix similarity do not provide a high
      performance. This paper presents a new approach to solving multi-class BCI
      classification problems by forming a subspace resembled from original subspaces
      and the proposed method for this approach is called Approximation-based Common
      Principal Component (ACPC). We perform experiments on Dataset 2a used in BCI
      Competition IV to evaluate the proposed method. This dataset was designed for
      motor imagery classification with 4 classes. Preliminary experiments show that
      the proposed ACPC feature extraction method when combining with Support Vector
      Machines outperforms CSP-based feature extraction methods on the experimental
      dataset. 

PMID- 24110874
TI  - Identification of a parametric, discrete-time model of ankle stiffness.
AB  - Dynamic ankle joint stiffness defines the relationship between the position of
      the ankle and the torque acting about it and can be separated into intrinsic and
      reflex components. Under stationary conditions, intrinsic stiffness can described
      by a linear second order system while reflex stiffness is described by
      Hammerstein system whose input is delayed velocity. Given that reflex and
      intrinsic torque cannot be measured separately, there has been much interest in
      the development of system identification techniques to separate them
      analytically. To date, most methods have been nonparametric and as a result there
      is no direct link between the estimated parameters and those of the stiffness
      model. This paper presents a novel algorithm for identification of a discrete
      time model of ankle stiffness. Through simulations we show that the algorithm
      gives unbiased results even in the presence of large, non-white noise.
      Application of the method to experimental data demonstrates that it produces
      results consistent with previous findings. 

PMID- 24110875
TI  - Subspace method decomposition and identification of the parallel-cascade model of
      ankle joint stiffness: theory and simulation.
AB  - This paper describes a state-space representation of the parallel-cascade model
      of ankle joint stiffness whose parameters are directly related to the underlying
      dynamics of the system. It then proposes a two step subspace method to identify
      this model. In the first step, the intrinsic stiffness is estimated using proper
      orthogonal projections. In the second step, the reflexive pathway is estimated by
      iterating between estimating its nonlinear and linear components. The identified
      models can be easily converted to continuous-time for physiological
      interpretation. Monte-Carlo studies using simulated data which replicate closely
      the experimental conditions, were used to compare the performance of the new
      method with the previous parallel-cascade, and subspace methods. The new method
      is more robust to noise and is guaranteed to converge. 

PMID- 24110876
TI  - Multi-step prediction of physiological tremor for robotics applications.
AB  - The performance of surgical robotic devices in real-time mainly depends on phase
      delay in sensors and filtering process. A phase delay of 16-20 ms is unavoidable
      in these robotics procedures due to the presence of hardware low pass filter in
      sensors and pre-filtering required in later stages of cancellation. To overcome
      this phase delay, we employ multi-step prediction with band limited multiple
      Fourier linear combiner (BMFLC) and Autoregressive (AR) methods. Results show
      that the overall accuracy is improved by 60% for tremor estimation compared to
      single-step prediction methods in the presence of phase delay. Experimental
      results with the proposed methods for 1-DOF tremor estimation highlight the
      improvement.

PMID- 24110877
TI  - Detection and removal of ocular artifacts from EEG signals for an automated REM
      sleep analysis.
AB  - Rapid eye movements (REMs) are a prominent feature of REM sleep, and their
      distribution and time density over the night represent important physiological
      and clinical parameters. At the same time, REMs produce substantial distortions
      on the electroencephalographic (EEG) signals, which strongly affect the
      significance of normal REM sleep quantitative study. In this work a new procedure
      for a complete and automated analysis of REM sleep is proposed, which includes
      both a REMs detection algorithm and an ocular artifact removal system. The two
      steps, based respectively on Wavelet Transform and adaptive filtering, are fully
      integrated and their performance is evaluated using REM simulated signals. Thanks
      to the integration with the detection algorithm, the proposed artifact removal
      system shows an enhanced accuracy in the recovering of the true EEG signal,
      compared to a system based on the adaptive filtering only. Finally the artifact
      removal system is applied to physiological data and an estimation of the actual
      distortion induced by REMs on EEG signals is supplied. 

PMID- 24110878
TI  - Classification of EEG bursts in deep sevoflurane, desflurane and isoflurane
      anesthesia using AR-modeling and entropy measures.
AB  - A study relating signal patterns of burst onsets in burst suppression EEG to the
      anesthetic agent or anesthesia induction protocol is presented. A dataset of 82
      recordings of sevoflurane, isoflurane and desflurane anesthesia underlies the
      study. 3 second segments from the onset of altogether 3214 bursts are described
      using AR model parameters, spectral entropy and sample entropy as features. The
      features are clustered using the K-means algorithm. The results indicate that no
      clear cut distinction can be made between the burst patterns induced by the
      mentioned anesthetics although bursts of certain properties are more common in
      certain patient groups. Several directions for further investigations are
      proposed based on visual inspection of the recordings. 

PMID- 24110879
TI  - Experiment-based scatter correction for cone-beam computed tomography using the
      statistical method.
AB  - Scatter signals in cone-beam computed tomography (CBCT) cause a significant
      problem that degrades image quality of reconstructed images, such as inaccuracy
      of CT numbers and cupping artifacts. In this paper, we will present an experiment
      based scatter correction method by pre-processing projection images using a
      statistical model combined with experimental kernels. The convolution kernels are
      estimated by using different thickness of PMMA plates attached to a beam stop
      lead sheet such that the scatter signal values can be measure in the shadow area
      of the projection images caused by the lead sheet. The scatter signal values of
      different thickness levels can be measured in the shadow area of projection
      images caused by the lead sheet. Then, the projection images are convolved with
      the kernels that are derived from the actual measurement of scatter signals in
      PMMA plates. Finally, the primary signals can be estimated using the maximum
      likelihood expectation maximization method. Experimental results by using the
      proposed method show that the quality of the reconstruction images is
      significantly improved. The CT numbers become more accurate and the cupping
      artifact is reduced. 

PMID- 24110880
TI  - A fast method for spine localization in x-ray images.
AB  - Detection of spines in medical images are important tasks in medical
      applications. These tasks are relatively easy for CT/MR images because the bones
      are easily distinguishable from other tissues. However, they are difficult for x
      ray images due to bone and soft tissue overlapping. This paper illustrates a
      method for detecting the medial axis of spine in x-ray images. Given an initial
      point on the spine in the x-ray image manually or automatically, the method
      iteratively searches for good feature points on the spine to locate the medial
      axis. As a result, the effort of determining the relevant medical information,
      such as Cobb's angle, can be minimized. The proposed method is fast and
      efficient. In average it took less than 1 second for localizing the spine on a
      3000*1000 gray scale x-ray image. 

PMID- 24110881
TI  - Volume registration based on 3-D phase correlation for tumor motion estimation in
      4-D CT.
AB  - This paper presents a three-dimensional (3-D) volume registration method that
      uses 3-D phase correlation to estimate the respiration-induced tumor motion in
      four-dimensional (4-D) thorax computed tomography (CT) for radiation therapy. The
      proposed method is an extension of 2-D phase correlation method to 3-D volume
      registration. Given two CT volumes obtained from different respiration stages,
      the tumor motion is modeled as a translational shift between the volumes. The 3-D
      phase correlation is obtained from the 3-D inverse Fourier transform of a
      normalized cross power spectrum of the volumes. The tumor motion along three
      directions is estimated by locating the highest peak in the 3-D phase
      correlation. In order to improve the estimation accuracy, we extend the 3-D phase
      correlation to sub-voxel accuracy. Experimental results demonstrate the
      effectiveness of the proposed method relative to a conventional 2-D phase
      correlation-based method. 

PMID- 24110882
TI  - Shape matching by integral invariants on eccentricity transformed images.
AB  - Matching occluded and noisy shapes is a frequently encountered problem in vision
      and medical image analysis and more generally in computer vision. To keep track
      of changes inside breast, it is important for a computer aided diagnosis system
      (CAD) to establish correspondences between regions of interest. Shape
      transformations, computed both with integral invariants and geodesic distance
      yield signatures that are invariant to isometric deformations, such as bending
      and articulations. Integral invariants are used on 2D planar shapes to describe
      the shape boundary. However, they provide no information about where a particular
      feature on the boundary lies with regard to overall shape structure. On the other
      hand, eccentricity transforms can be used to match shapes by signatures of
      geodesic distance histograms based on information from inside the shape; but they
      ignore the boundary information. We describe a method that combines both the
      boundary signature of shape obtained from integral invariants and structural
      information from the eccentricity transform to yield improved results. 

PMID- 24110883
TI  - A realistic computed tomography simulator for small motion analysis of cerebral
      aneurysms.
AB  - This paper describes a realistic simulator for the Computed Tomography (CT) scan
      process for motion analysis. In fact, we are currently developing a new framework
      to find small motion from the CT scan. In order to prove the fidelity of this
      framework, or potentially any other algorithm, we present in this paper a
      simulator to simulate the whole CT acquisition process with a priori known
      parameters. In other words, it is a digital phantom for the motion analysis that
      can be used to compare the results of any related algorithm with the ground-truth
      realistic analytical model. Such a simulator can be used by the community to test
      different algorithms in the biomedical imaging domain. The most important
      features of this simulator are its different considerations to simulate the best
      the real acquisition process and its generality. 

PMID- 24110884
TI  - Iterative image reconstruction for ultra-low-dose CT with a combined low-mAs and
      sparse-view protocol.
AB  - Ultra-low-dose x-ray computed tomography (CT) imaging is needed in CT fields.
      Through a scan protocol by lowering the milliampere-seconds (mAs) and reducing
      the number of projections per rotation around the body, we can realize low-dose
      CT imaging. However, the resulting noisy and insufficient measurements will
      unavoidably cause the degradation of desired-image. To solve this problem,
      iterative image reconstruction is a promising choice for achieving high-quality
      image with a low-dose scan. In this study, we are focusing on ultra-low-dose CT
      image reconstruction by using penalized weighted least-square (PWLS) criteria
      with a combined low-mAs and sparse-view protocol. Specifically, the sinogram data
      acquired with a combined low-mAs and sparse-view protocol is first restored by
      using a PWLS based sinogram restoration method. Then, the restored sinogram data
      is hereafter used to reconstruct image by using a PWLS based total variation
      (PWLS-TV) method. Qualitative and quantitative evaluations by simulations were
      carried out to validate the present method. 

PMID- 24110885
TI  - Fully automated segmentation of corpus callosum in midsagittal brain MRIs.
AB  - In the diagnosis of various brain disorders by analyzing the brain magnetic
      resonance images (MRI), the segmentation of corpus callosum (CC) is a crucial
      step. In this paper, we propose a fully automated technique for CC segmentation
      in the T1-weighted midsagittal brain MRIs. An adaptive mean shift clustering
      technique is first used to cluster homogenous regions in the image. In order to
      distinguish the CC from other brain tissues, area analysis, template matching, in
      conjunction with the shape and location analysis are proposed to identify the CC
      area. The boundary of detected CC area is then used as the initial contour in the
      Geometric Active Contour (GAC) model, and evolved to get the final segmentation
      result. Experimental results demonstrate that the proposed technique overcomes
      the problem of manual initialization in existing GAC technique, and provides a
      reliable segmentation performance. 

PMID- 24110886
TI  - Simultaneous label fusion with vessel preserving for bone removal in CT
      angiography scans.
AB  - When visualizing vessels with CT angiography scans, the arteries are often
      obstructed by bones. Traditional methods require an additional non-enhanced scan
      to acquire a bone mask which is then subtracted from the original CTA scan. In
      this study, we present an automated bone removal method using only contrast
      enhanced scans based on simultaneous label fusion. We build an atlas database
      where each atlas is paired with a bone label and a vessel label. After the
      atlases are mapped to a subject, we propose a vessel preserving scheme to protect
      possible vessel areas from bone removal by simultaneous label fusion. Seven
      clinical data sets were used for validation and the results showed that this
      method can achieve consistent and thorough bone removal with maximal vessels
      preservation. 

PMID- 24110887
TI  - A robust semi-automatic approach for ROI segmentation in 3D CT images.
AB  - In CT-based clinical applications, segmentation of regions of interest (ROIs) is
      a preliminary but vital step. The task is, however, quite challenging, especially
      for 3D objects, because suspicious ROIs are usually soft-tissue structures, which
      include a various organs and anatomical objects while sharing a small intensity
      dynamic range in CT images. Furthermore, the ROIs usually vary significantly in
      size, shape, and boundary conditions. Among considerable efforts contributed to
      addressing the problem, live wire, also known as intelligent scissors, has been
      recognized as an efficient and robust tool for dealing with a wide range of 2D
      ROIs. Such an approach provides full user control during the process while
      minimizing human interaction to optimally counterbalance automatic and manual
      approaches. In this work, we improve our previous live-wire-based segmentation of
      3D objects and the experiment results show its efficiency and robustness. 

PMID- 24110888
TI  - Non-Euclidean basis function based level set segmentation with statistical shape
      prior.
AB  - We present a new framework for image segmentation with statistical shape model
      enhanced level sets represented as a linear combination of non-Euclidean radial
      basis functions (RBFs). The shape prior for the level set is represented as a
      probabilistic map created from the training data and registered with the target
      image. The new framework has the following advantages: 1) the explicit RBF
      representation of the level set allows the level set evolution to be represented
      as ordinary differential equations and reinitialization is no longer required. 2)
      The non-Euclidean distance RBFs makes it possible to incorporate image
      information into the basis functions, which results in more accurate and
      topologically more flexible solutions. Experimental results are presented to
      demonstrate the advantages of the method, as well as critical analysis of level
      sets versus the combination of both methods. 

PMID- 24110889
TI  - Ultrasound contrast image segmentation using a modified level set method.
AB  - Manual segmentation of ultrasound contrast images is time-consuming and
      inevitable to variability, and computer-based segmentation algorithms often
      require user interaction. This paper proposes a novel level set model for fully
      automated segmentation of vascular ultrasound contrast images. The initial
      contour of arterial boundaries is acquired based on an automatic procedure. The
      level set model moves the initial contour towards the boundaries of arterial
      inner wall based on minimization of the energy function. The traditional energy
      function is improved by introducing an edge detector based on image gradient and
      the standard difference image. Both spatial and temporal information of the image
      are considered, and the robustness and accuracy of the level set model is
      enhanced. Ultrasonic contrast images of living mouse are acquitted with high
      frequency ultrasound system. Images of carotid arteries are processed with our
      method. The segmentation results using the proposed method are evaluated against
      two observers' hand-outlined boundaries, showing that computer-generated
      boundaries agree well with the observers' hand-outlined boundaries as much as the
      different observers agree with each other. 

PMID- 24110890
TI  - Local binary fitting energy solution by graph cuts for MRI segmentation.
AB  - This paper proposes a new solution for local binary fitting energy minimization
      based on graph cuts for automatic brain structure segmentation on magnetic
      resonance images. The approach establishes an effective way to embed the energy
      formulation into a directed graph, such that the energy is minimized by
      maximizing the graph flow. Proposed and conventional solutions are compared by
      segmenting the well-known BrainWeb synthetic brain Magnetic Resonance Imaging
      database. Achieved results show an improvement on the computational cost (about
      10 times shorter) while maintaining the segmentation accuracy (96%). 

PMID- 24110891
TI  - Three-dimensional quantitative microwave imaging of realistic numerical breast
      phantoms using Huber regularization.
AB  - Breast tumor detection with microwaves is based on the difference in dielectric
      properties between normal and malignant tissues. The complex permittivity
      reconstruction of inhomogeneous dielectric biological tissues from microwave
      scattering is a nonlinear, ill-posed inverse problem. We proposed to use the
      Huber regularization in our previous work where some preliminary results for
      piecewise constant objects were shown. In this paper, we employ the Huber
      function as regularization in the even more challenging 3D piecewise continuous
      case of a realistic numerical breast phantom. The resulting reconstructions of
      complex permittivity profiles indicate potential for biomedical imaging. 

PMID- 24110892
TI  - Accuracy and uncertainty of asymmetric magnetization transfer ratio
      quantification for amide proton transfer (APT) imaging at 3T: a Monte Carlo
      study.
AB  - Amide proton transfer (APT) imaging offers a novel and powerful MRI contrast
      mechanism for quantitative molecular imaging based on the principle of chemical
      exchange saturation transfer (CEST). Asymmetric magnetization transfer ratio
      (MTR(asym)) quantification is crucial for Z-spectrum analysis of APT imaging, but
      is still challenging, particularly at clinical field strength. This paper studies
      the accuracy and uncertainty in the quantification of MTR(asym) for APT imaging
      at 3T, by using high-order polynomial fitting of Z-spectrum through Monte Carlo
      simulation. Results show that polynomial fitting is a biased estimator that
      consistently underestimates MTR(asym). For a fixed polynomial order, the accuracy
      of MTR(asym) is almost constant with regard to signal-to-noise ratio (SNR) while
      the uncertainty decreases exponentially with SNR. The higher order polynomial
      fitting increases both the accuracy and the uncertainty of MTR(asym). For
      different APT signal intensity levels, the relative accuracy and the absolute
      uncertainty keep constant for a fixed polynomial order. These results indicate
      the limitations and pitfalls of polynomial fitting for MTR(asym) quantification
      so better quantification technique for MTR(asym) estimation is warranted.

PMID- 24110893
TI  - Iterative reconstruction of CT images on GPUs.
AB  - Although widely used in nuclear medicine (gamma-camera, single photon emission
      computed tomography (SPECT), positron emission tomography (PET)), iterative
      reconstruction has not yet penetrated in CT. The main reason for this is that
      data sets in CT are much larger than in nuclear medicine and iterative
      reconstruction then becomes computationally very intensive. Graphical Processing
      Units (GPUs) provide the possibility to reduce effectively the high computational
      cost of their implementation. It is the goal of this work to develop a GPU-based
      algorithm to reconstruct high quality images from under sampled and noisy
      projection data. 

PMID- 24110894
TI  - EGS5 simulations to design a Ce:GAGG scintillator based Compton camera.
AB  - Ce(+3): Gd3Al2Ga3O12 (Ce:GAGG) is expected to be promising scintillator for PET,
      SPECT, and gamma camera applications because of its attractive properties. We
      designed a Compton camera based on Ce:GAGG, both as scatterer and absorber, for
      imaging and radioactivity measurement of point sources. The two important
      parameters sensitivity and spatial resolution are determined for 4 * 4 pixels,
      each pixel of size 1 * 1 cm(2), for both scatterer and absorber. Our main focus
      in this paper is to image a distant source for which sensitivity is of prime
      importance. High sensitivity and light weight are two important advantages of
      Compton camera for distant source imaging and the availability of Ce:GAGG 3 * 3
      mm(2) pixel size is expected to give a spatial resolution of ~ 5 mm for medical
      applications as well.

PMID- 24110895
TI  - Energy back-projective composition for 3-D coronary artery reconstruction.
AB  - This paper presents a novel energy back-projective composition model (EBPCM) for
      3-D reconstruction of the coronary arteries from two mono-plane angiographic
      images. A major problem with the commonly used parameter deformable model is that
      the predefined correspondences may become non-strict matching after the curve
      evolution, which generally leads to large extra calculation errors. In this
      study, the energy field in the image is back-projected to 3-D space and
      decomposed into three independent components in the world coordinates centered at
      the iso-center of the C-arm. Then, the components from different views are
      composited together according to the rotation and scaling relationship of the
      imaging angles. The composited energy field hence is utilized as the external
      force to control the evolution of the vascular structure in 3-D space. As the
      driving force is iteratively updated according to energy in the two projection
      images, the non-strict matching can be effectively avoided. Also, the proposed
      method is very flexible, which can be composited with any energy fields such as
      Generalized Gradient Vector Flow (GGVF) and Potential Energy (PE) etc.
      Experiments demonstrate that the proposed method is very effective and robust,
      when using GGVF as the external force, the reconstruction RMS error can be
      reduced to about 0.595 mm in the 3-D space.

PMID- 24110896
TI  - Noise behavior of MR brain reconstructions using compressed sensing.
AB  - Compressed sensing (CS) has demonstrated great potential to reconstruct high
      quality MR images from undersampled k-space data. However, successful application
      of CS in clinic is still limited by many factors. One of the key factors is that
      the noise behavior in CS reconstructions remains largely unexplored. The main
      objective of this work is to analyze the noise behavior of MR reconstructions
      using CS method with different reduction factors. Our work focuses on brain CS
      MRI reconstructions using non-linear conjugate gradient (NLCG) solvers. After
      reconstruction, the noise behavior is characterized using the MP-Law method. The
      results show that the spatial noise distributed non-uniformly, and the noise
      variance from CS reconstruction increases with reduction factors. A kind of
      fitting model is given, which can be used to predict the noise behavior parameter
      for different reduction factors, and the noise amplification factor maps are
      shown to prove the denoising capability of CS reconstruction. The results provide
      a qualitative and quantitative understanding of the noise behavior in CS-MRI with
      different reduction factors. 

PMID- 24110897
TI  - Microfabricated polymer-based neural interface for electrical
      stimulation/recording, drug delivery, and chemical sensing--development.
AB  - We present here a microfabricated, multi-functional neural interface with the
      ability to selectively apply electrical and chemical stimuli, while
      simultaneously monitoring both electrical and chemical activity in the brain.
      Such a comprehensive approach is required to understand and treat
      neuropsychiatric disorders, such as major depressive disorder (MDD), and to
      understand the mechanisms underlying treatments, such as pharmaceutical therapies
      and deep brain stimulation (DBS). The polymer-based, multi-functional neural
      interface is capable of electrical stimulation and recording, targeted drug
      delivery, and electrochemical sensing. A variety of different electrode and
      fluidic channel arrangements are possible with this fabrication process.
      Preliminary testing has shown the suitability of these neural interfaces for in
      vivo electrical stimulation and recording, as well as in vitro chemical sensing.
      Testing of the in vitro drug delivery and combined in vivo functionalities this
      neural interface are currently underway. 

PMID- 24110898
TI  - An improved system approach towards future cochlear implants.
AB  - Cochlear implants (CIs) have been used for many years to restore hearing for deaf
      patients. Unfortunately, today's CIs are still bulky devices and uncomfortable to
      wear. In this paper we present three innovations that ultimately should pave the
      way to a fully implantable bionic ear. First a microfabrication process used to
      fabricate the polymer metal microelectrode array for auditory nerve stimulation
      is discussed. Subsequently, a compact biphasic programmable stimulator chip to be
      used along with this electrode array is presented. By using a double loop
      feedback circuit topology, the circuit provides a precise stimulation current
      while requiring only little voltage headroom. The resulting low power consumption
      and reduced chip area allow for integration of the electronic circuitry onto the
      electrode array. Finally, as reliability and data transmission rate are two of
      the most critical issues in CI devices, we propose a software method to improve
      both data rate and reliability of transmitting digital data from the external
      part of the CI to the internal part with negligible power consumption. 

PMID- 24110900
TI  - A MedRadio-band low-energy-per-bit 4-Mbps CMOS OOK receiver for implantable
      medical devices.
AB  - A 4-Mbps 400-MHz On-Off Keying (OOK) receiver implemented in 0.18-um CMOS
      technology for implantable epilepsy sense-and-stimulation devices is presented.
      The proposed receiver is composed of a new current-mode full-wave envelope
      detector and differential cascaded gain amplifiers which is operated at MedRadio
      band. The fabricated receiver has power consumption of 0.27 mW and energy
      consumption of 0.07 nJ per bit at 4-Mbps. The sensitivity of receiver is -45.67
      dBm.

PMID- 24110901
TI  - Experimental implant communication of high data rate video using an ultra
      wideband radio link.
AB  - Ultra wideband (UWB) is one of the radio technologies adopted by the IEEE
      802.15.6TM-2012 standard for on-body communication in body area networks (BANs).
      However, a number of simulation-based studies suggest the feasibility of using
      UWB for high data rate implant communication too. This paper presents an
      experimental verification of said predictions. We carried out radio transmissions
      of H.264/1280*720 pixels video at 80 Mbps through a UWB multiband orthogonal
      frequency division multiplexing (MB-OFDM) interface in a porcine chirurgical
      model. The results demonstrated successful transmission up to a maximum depth of
      30 mm in the abdomen and 33 mm in the thorax within the 4.2-4.8 GHz frequency
      band. 

PMID- 24110902
TI  - Electromagnetic and thermal effects of IR-UWB wireless implant systems on the
      human head.
AB  - The usage of implanted wireless transmitting devices inside the human body has
      become widely popular in recent years. Applications such as multi-channel neural
      recording systems require high data rates in the wireless transmission link.
      Because of the inherent advantages provided by Impulse-Radio Ultra Wide Band (IR
      UWB) such as high data rate capability, low power consumption and small form
      factor, there has been an increased research interest in using IR-UWB for bio
      medical implant applications. Hence it has become imperative to analyze the
      electromagnetic effects caused by the use of IR-UWB when it is operated in or
      near the human body. This paper reports the electromagnetic effects of head
      implantable transmitting devices operating based on Impulse Radio Ultra Wide Band
      (IR-UWB) wireless technology. Simulations illustrate the performance of an
      implantable UWB antenna tuned to operate at 4 GHz with an -10 dB bandwidth of
      approximately 1 GHz when it is implanted in a human head model. Specific
      Absorption Rate (SAR), Specific Absorption (SA) and temperature increase are
      analyzed to compare the compliance of the transmitting device with international
      safety regulations.

PMID- 24110903
TI  - A wireless ECG acquisition and classification system for body sensor networks.
AB  - This paper demonstrates a wireless ECG acquisition and classification system with
      a bio-signal processor (BSP), a super regenerative transceiver, and a digital
      signal processor (DSP). The BSP, which is implemented with low complexity
      architecture, includes only a low noise amplifier with chopping techniques and a
      high-pass sigma-delta modulator (HPSDM). The super-regenerative on-off keying
      (OOK) transceiver is applied for the low power, short range transmission and low
      date rate wireless communication. For the signal processing and analyzing, the
      DSP circuit is adopted in the receiver. The whole system is implemented in a TSMC
      0.18 um 1P6M CMOS process under the supply voltage of 1.2 V. In the near body
      node, the power consumption including a BSP and a transmitter is 587 uW only.
      With two PR44 zinc-air batteries of 605 mAh, the near body node circuit can be
      operated about 100 days. In the receiving node, the power consumption with a
      receiver and a DSP is 926 uW.

PMID- 24110904
TI  - Indoor inertial waypoint navigation for the blind.
AB  - Indoor navigation technology is needed to support seamless mobility for the
      visually impaired. This paper describes the construction and evaluation of an
      inertial dead reckoning navigation system that provides real-time auditory
      guidance along mapped routes. Inertial dead reckoning is a navigation technique
      coupling step counting together with heading estimation to compute changes in
      position at each step. The research described here outlines the development and
      evaluation of a novel navigation system that utilizes information from the mapped
      route to limit the problematic error accumulation inherent in traditional dead
      reckoning approaches. The prototype system consists of a wireless inertial sensor
      unit, placed at the users' hip, which streams readings to a smartphone processing
      a navigation algorithm. Pilot human trials were conducted assessing system
      efficacy by studying route-following performance with blind and sighted subjects
      using the navigation system with real-time guidance, versus offline verbal
      directions. 

PMID- 24110905
TI  - Development of a low-cost wireless monitoring system supporting the continuity of
      medical care of the patient at home.
AB  - The fusion of Biomedical Technology, Informatics and Medical Decision-making into
      the modern Clinical Decision Support Systems (CDSS), as well as the population
      ageing and the escalation of hospital costs are the driving forces for adopting
      decentralized systems of health care provision. One of the main problems arising
      with decentralized health care provision, such as Home Care, is the discontinuity
      of medical care. This discontinuity appears not only in medical data transfer,
      but also in the quality of medical supervision. In order to accommodate for the
      lack of sufficient medical supervision in Home-Care environment, we have
      developed low-cost prototype solution for monitoring basic physiological
      parameters. The implemented architecture is employing wearable biomedical signal
      acquisition modules, utilizing "off the shelf" technologies in order to minimize
      cost. These modules transmit the acquired vital signs through a wireless link to
      a laptop computer. A web application allows continuous quasi real-time
      supervision of patient's biosignals from any PC equipped with a web browser and
      appropriate authorization codes. 

PMID- 24110906
TI  - Bit error rate estimation for galvanic-type intra-body communication using
      experimental eye-diagram and jitter characteristics.
AB  - Bit error rate (BER), which indicates the reliability of communicate channel, is
      one of the most important values in all kinds of communication system, including
      intra-body communication (IBC). In order to know more about IBC channel, this
      paper presents a new method of BER estimation for galvanic-type IBC using
      experimental eye-diagram and jitter characteristics. To lay the foundation for
      our methodology, the fundamental relationships between eye-diagram, jitter and
      BER are first reviewed. Then experiments based on human lower arm IBC are carried
      out using quadrature phase shift keying (QPSK) modulation scheme and 500 KHz
      carries frequency. In our IBC experiments, the symbol rate is from 10 Ksps to 100
      Ksps, with two transmitted power settings, 0 dBm and -5 dBm. Finally, the BER
      results were obtained after calculation by experimental data through the
      relationships among eye-diagram, jitter and BER. These results are then compared
      with theoretical values and they show good agreement, especially when SNR is
      between 6 dB to 11 dB. Additionally, these results demonstrate assuming the noise
      of galvanic-type IBC channel as Additive White Gaussian Noise (AWGN) in previous
      study is applicable. 

PMID- 24110907
TI  - Using wearable UWB radios to measure foot clearance during walking.
AB  - Foot clearance above ground is a key factor for a better understanding of the
      complicated relationship between falls and gait. This paper proposes a wearable
      system using UWB transceivers to monitor the vertical heel/toe clearance during
      walking. First, a pair of very small and light antennas is placed on a point
      approximating to the heel/toe of the foot, acting as a transmitter and receiver.
      Then, the reflected signal from ground is captured and propagation delay is
      detected using noise suppressed Modified-Phase-Only-Correlator (MPOC). The
      performance of the UWB-based system was compared with an ultrasound system for
      stationary movements. The experimental results show that an overall mean
      difference between these two systems is about 0.634mm with correlation
      coefficient value of 0.9604. The UWB-based system is then used to measure foot
      clearance during walking which shows promising results for gait events detection.

PMID- 24110908
TI  - Ballistocardiography with fiber optic sensor in headrest position: a feasibility
      study and a new processing algorithm.
AB  - Ballistocardiography (BCG) is a promising unobtrusive method for home e
      healthcare systems, and has attracted increasing interest in recent years along
      with technological advances in related biomedical, electrical engineering and
      computer science fields. While existing systems have investigated the efficacy of
      BCG setups in bed, backrest, seat or scale positions, we propose to study BCG in
      headrest position that will allow new practical and portable applications. To
      this end, we designed and implemented a multi-modality sensing system including a
      high-sensitivity microbend fiber optic BCG sensor. In this preliminary study, we
      have collected multi-modality physiological data on 3 human subjects. We ran
      extensive analysis on BCG in correlation with ECG, and identified special
      characteristics of the signal in the new BCG setup. The result suggests that new
      appropriate computing techniques are necessary for accurately recovering the
      heart beat signal. Therefore, we developed a novel algorithm for heart beat
      detection. We evaluate the algorithm with the data and demonstrate that it can
      accurately compute heart rate intervals in the headrest BCG despite significant
      signal distortion. 

PMID- 24110909
TI  - Mechanical ventilation system monitoring: automatic detection of dynamic
      hyperinflation and asynchrony.
AB  - Automatic monitoring of mechanical ventilation system becomes more and more
      important with respect to the number of patients per clinician. In this paper,
      the automatic detections of dynamic hyperinflation (PEEPi) and asynchrony in a
      monitoring framework are considered. The proposed detection methods are based on
      a robust non-parametric hypothesis testing, namely Random Distortion Testing
      (RDT), that requires no prior information on the signal distribution. The
      experiment results have shown that the proposed algorithms provide relevant
      detection of abnormalities during mechanical ventilation. 

PMID- 24110910
TI  - Real-time noninvasive estimation of intrapleural pressure in mechanically
      ventilated patients: a feasibility study.
AB  - A method for real-time noninvasive estimation of intrapleural pressure in
      mechanically ventilated patients is proposed. The method employs a simple first
      order lung mechanics model that is fitted in real-time to flow and pressure
      signals acquired non-invasively at the opening of the patient airways, in order
      to estimate lung resistance (RL), lung compliance (CL) and intrapleural pressure
      (Ppl) continuously in time. Estimation is achieved by minimizing the sum of
      squared residuals between measured and model predicted airway pressure using a
      modified Recursive Least Squares (RLS) approach. Particularly, two different RLS
      algorithms, namely the conventional RLS with Exponential Forgetting (EF-RLS) and
      the RLS with Vector-type Forgetting Factor (VFF-RLS), are considered in this
      study and their performances are first evaluated using simulated data.
      Simulations suggest that the conventional EF-RLS algorithm is not suitable for
      our purposes, whereas the VFF-RLS method provides satisfactory results. The
      potential of the VFF-RLS based method is then proved on experimental data
      collected from a mechanically ventilated pig. Results show that the method
      provides continuous estimated lung resistance and compliance in normal
      physiological ranges and pleural pressure in good agreement with invasive
      esophageal pressure measurements. 

PMID- 24110911
TI  - Cough sound analysis - a new tool for diagnosing pneumonia.
AB  - Pneumonia kills over 1,800,000 children annually throughout the world. Prompt
      diagnosis and proper treatment are essential to prevent these unnecessary deaths.
      Reliable diagnosis of childhood pneumonia in remote regions is fraught with
      difficulties arising from the lack of field-deployable imaging and laboratory
      facilities as well as the scarcity of trained community healthcare workers. In
      this paper, we present a pioneering class of enabling technology addressing both
      of these problems. Our approach is centered on automated analysis of cough and
      respiratory sounds, collected via microphones that do not require physical
      contact with subjects. We collected cough sounds from 91 patients suspected of
      acute respiratory illness such as pneumonia, bronchiolitis and asthma. We
      extracted mathematical features from cough sounds and used them to train a
      Logistic Regression classifier. We used the clinical diagnosis provided by the
      paediatric respiratory clinician as the gold standard to train and validate our
      classifier against. The methods proposed in this paper could separate pneumonia
      from other diseases at a sensitivity and specificity of 94% and 75% respectively,
      based on parameters extracted from cough sounds alone. Our method has the
      potential to revolutionize the management of childhood pneumonia in remote
      regions of the world. 

PMID- 24110912
TI  - Hierarchical individualization of a recruitment model with a viscoelastic
      component for ARDS patients.
AB  - Patient-specific mathematical models of respiratory mechanics enable substantial
      insight into patient state and pulmonary dynamics that are not directly
      measurable. Thus they offer potential e.g. to predict the outcome of ventilator
      settings for Acute Respiratory Distress Syndrome (ARDS) patients. In this work,
      an existing static recruitment model is extended by viscoelastic components
      allowing model simulations in various ventilation scenarios. A hierarchical
      approach is used to identify the model with measured data of 12 ARDS patients
      under static and dynamic conditions. Identified parameter values were
      physiologically plausible and reproduced the measured pressure responses with a
      median Coefficient of Determination (CD) of 0.972 in the dynamic and 0.992 in the
      static maneuver. Overall, the model presented incorporates physiological
      mechanisms, captures ARDS dynamics and viscoelastic tissue properties and is
      valid under various ventilation patterns. 

PMID- 24110913
TI  - Model-based respiratory mechanics to titrate PEEP and monitor disease state for
      experimental ARDS subjects.
AB  - Modelling the respiratory mechanics of mechanically ventilated (MV) patients can
      provide useful information to guide MV therapy. Two model-based methods were
      evaluated based on data from three experimental acute respiratory distress
      syndrome (ARDS) induced piglets and validated against values available from
      ventilators. A single compartment lung model with integral-based parameter
      identification was found to be effective in capturing fundamental respiratory
      mechanics during inspiration. The trends matched clinical expectation and
      provided better resolution than clinically derived linear model metrics. An
      expiration time constant model also captured the same trend in respiratory
      elastance. However, the assumption of constant resistance and a slightly higher
      fitting error results in less insight than the single compartment model. Further
      research is required to confirm its application in titrating to optimal MV
      settings. 

PMID- 24110914
TI  - Study of the oscillatory breathing pattern in elderly patients.
AB  - Some of the most common clinical problems in elderly patients are related to
      diseases of the cardiac and respiratory systems. Elderly patients often have
      altered breathing patterns, such as periodic breathing (PB) and Cheyne-Stokes
      respiration (CSR), which may coincide with chronic heart failure. In this study,
      we used the envelope of the respiratory flow signal to characterize respiratory
      patterns in elderly patients. To study different breathing patterns in the same
      patient, the signals were segmented into windows of 5 min. In oscillatory
      breathing patterns, frequency and time-frequency parameters that characterize the
      discriminant band were evaluated to identify periodic and non-periodic breathing
      (PB and nPB). In order to evaluate the accuracy of this characterization, we used
      a feature selection process, followed by linear discriminant analysis. 22 elderly
      patients (7 patients with PB and 15 with nPB pattern) were studied. The following
      classification problems were analyzed: patients with either PB (with and without
      apnea) or nPB patterns, and patients with CSR versus PB, CSR versus nPB and PB
      versus nPB patterns. The results showed 81.8% accuracy in the comparisons of nPB
      and PB patients, using the power of the modulation peak. For the segmented
      signal, the power of the modulation peak, the frequency variability and the
      interquartile ranges provided the best results with 84.8% accuracy, for
      classifying nPB and PB patients. 

PMID- 24110915
TI  - Identifying positive roles for endogenous stochastic noise during computation in
      neural systems.
AB  - Information processing in nonlinear systems can sometimes be enhanced by the
      presence of stochastic fluctuations, or noise. Although the electrical properties
      of neurons and synapses are known to be influenced by intrinsic stochastic
      variability, it remains an open question as to whether living systems exploit
      this noise during neuronal information processing. This is despite various forms
      of noise-enhanced processing, such as classical stochastic resonance, having been
      observed in mathematical models of neural systems and in data acquired
      experimentally. We recently argued that advancing our understanding of the
      potential roles of random noise in assisting neuronal information processing will
      require specific focus on a concrete hypothesis about the computational roles of
      a specific neural system that can then be tested experimentally using signals and
      metrics relevant to the hypothesis. In this invited symposium paper, we argue why
      most existing approaches to studying stochastic resonance based on classical
      definitions and methods are highly limited in their applicability, since they
      impose an implied computational hypothesis that may have little relevance for
      real neurobiological systems. 

PMID- 24110916
TI  - Stochastic resonance occurring in tactile sensation of human finger.
AB  - In this paper, we review the influence of external noise on human tactile
      sensation as outlined in prior and current studies. In the last few decades,
      researchers have found that, although noise is always considered detrimental, it
      provides the benefit of stochastic resonance (SR) phenomena. Based on previous
      studies, we investigate the effect of the SR phenomenon on human tactile
      sensation. In this context, we developed a system consisting of an experimental
      apparatus and a computer program, and performed a series of psychophysical
      experiments using different types of stimulus with normal vibration. The
      experimental results show that tactile sensation precision can be enhanced by an
      appropriate level of external noise. Furthermore, we introduce a neural network
      model composed of nonlinear neurons with a bi-stable equilibrium condition to
      clarify the result. Finally, we perform a sequence of psychophysical experiments
      with tangential vibration to clarify which conditions of vibration direction and
      stimulus size cause the strongest SR. The results show that the normal difference
      limen (DL) is significantly affected by stimulus point size. On the other hand,
      neither normal nor tangential DL is significantly affected by stimulus point
      size. Moreover, the characteristics of SR with normal vibration are quite
      different from those with tangential vibration. 

PMID- 24110917
TI  - Effects of electrical noise to a knee joint on quiet bipedal stance and treadmill
      walking.
AB  - The present study assessed whether an unperceivable, noise-like electrical
      stimulation of a knee joint enhances the stability of quiet bipedal stance and
      treadmill walking in young subjects. The results showed that the slow postural
      sway measures in quiet bipedal stance were significantly reduced by the
      electrical noise (P<0.05). In the treadmill walking, low frequency component
      (below 1 Hz) of mediolateral acceleration, measured at the third lumbar vertebra,
      significantly decreased with the electrical noise (P<0.05), while there were no
      changes in the anteroposterior and vertical directions. These results indicate
      that the electrical noise to a knee joint can be applied to enhance postural
      control in quiet bipedal stance and treadmill walking. 

PMID- 24110918
TI  - Reverse stochastic resonance in a hippocampal CA1 neuron model.
AB  - Stochastic resonance (SR) is a ubiquitous and counter- intuitive phenomenon
      whereby the addition of noise to a non-linear system can improve the detection of
      sub-threshold signals. The "signal" is normally periodic or deterministic whereas
      the "noise" is normally stochastic. However, in neural systems, signals are often
      stochastic. Moreover, periodic signals are applied near neurons to control neural
      excitability (i.e. deep brain stimulation). We therefore tested the hypothesis
      that a quasi-periodic signal applied to a neural network could enhance the
      detection of a stochastic neural signal (reverse stochastic resonance). Using
      computational methods, a CA1 hippocampal neuron was simulated and a Poisson
      distributed subthreshold synaptic input ("signal") was applied to the synaptic
      terminals. A periodic or quasi periodic pulse train at various frequencies
      ("noise") was applied to an extracellular electrode located near the neuron. The
      mutual information and information transfer rate between the output and input of
      the neuron were calculated. The results display the signature of stochastic
      resonance with information transfer reaching a maximum value for increasing power
      (or frequency) of the "noise". This result shows that periodic signals applied
      extracellularly can improve the detection of subthreshold stochastic neural
      signals. The optimum frequency (110 Hz) is similar to that used in patients with
      Parkinson's suggesting that this phenomenon could play a role in the therapeutic
      effect of high frequency stimulation.

PMID- 24110919
TI  - Effects of the rates of pseudo-spontaneous spikes generated by electric stimuli
      on information transmission in an auditory nerve fiber model.
AB  - In this study, the effects of the rate of pseudo-spontaneous spikes on
      information transmission of the spike trains in response to the electric
      pulsatile stimulus currents in an auditory nerve fiber (ANF) model is
      investigated through computer simulation. The pseudo-spontaneous spikes can be
      generated by high rate pulsatile electric stimuli, making it possible to
      efficiently encode sound stimuli into the spike trains of the ANF in cochlear
      prostheses. In this investigation, the information rate of the spike trains in
      response to sinusoidally modulated pulsatile electric stimuli was estimated as
      the amplitude of the pulsatile electric stimuli (the rate of pseudo-spontaneous
      spikes) was varied. The results show that the information rates increased,
      reached a maximum, and then decreased, in several different values of modulation
      depth, as the rate of pseudo-spontaneous spikes increased. This may imply a
      resonance phenomenon dependent on the rate of pseudo-spontaneous spikes generated
      by electric stimuli in the ANF model. These findings may play a key role in the
      design of better cochlear prostheses. 

PMID- 24110920
TI  - Feature extraction and unsupervised classification of neural population reward
      signals for reinforcement based BMI.
AB  - New reinforcement based paradigms for building adaptive decoders for Brain
      Machine Interfaces involve using feedback directly from the brain. In this work,
      we investigated neuromodulation in the Nucleus Accumbens (reward center) during a
      multi-target reaching task and investigated how to extract a reinforcing or non
      reinforcing signal that could be used to adapt a BMI decoder. One of the
      challenges in brain-driven adaptation is how to translate biological
      neuromodulation into a single binary signal from the distributed representation
      of the neural population, which may encode many aspects of reward. To extract
      these signals, feature analysis and clustering were used to identify timing and
      coding properties of a user's neuromodulation related to reward perception.
      First, Principal Component Analysis (PCA) of reward related neural signals was
      used to extract variance in the firing and the optimum time correlation between
      the neural signal and the reward phase of the task. Next, k-means clustering was
      used to separate data into two classes. 

PMID- 24110921
TI  - A BCI using VEP for continuous control of a mobile robot.
AB  - A brain-computer interface (BCI) translates brain activity into commands to
      control devices or software. Common approaches are based on visual evoked
      potentials (VEP), extracted from the electroencephalogram (EEG) during visual
      stimulation. High information transfer rates (ITR) can be achieved using (i)
      steady-state VEP (SSVEP) or (ii) code-modulated VEP (c-VEP). This study
      investigates how applicable such systems are for continuous control of robotic
      devices and which method performs best. Eleven healthy subjects steered a robot
      along a track using four BCI controls on a computer screen in combination with
      feedback video of the movement. The average time to complete the tasks was (i)
      573.43 s and (ii) 222.57 s. In a second non-continuous trial-based validation run
      the maximum achievable online classification accuracy over all subjects was (i)
      91.36 % and (ii) 98.18 %. This results show that the c-VEP fits the needs of a
      continuous system better than the SSVEP implementation. 

PMID- 24110922
TI  - Shared-control brain-computer interface for a two dimensional reaching task using
      EEG error-related potentials.
AB  - One of the main problems of EEG-based brain computer interfaces (BCIs) is their
      low information rate, thus for complex tasks the user needs large amounts of time
      to solve the task. In an attempt to reduce this time and improve the application
      robustness, recent works have explored shared-control strategies where the device
      does not only execute the decoded commands, but it is also involved in executing
      the task. This work proposes a shared-control BCI using error potentials for a 2D
      reaching task with discrete actions and states. The proposed system has several
      interesting properties: the system is scalable without increasing the complexity
      of the user's mental task; the interaction is natural for the user, as the mental
      task is to monitor the device performance to promote its task learning (in this
      context the reaching task); and the system has the potential to be combined with
      additional brain signals to recover or learn from interaction errors. Online
      control experiments were performed with four subjects, showing that it was
      possible to reach a goal location from any starting point within a 5*5 grid in
      around 23 actions (about 19 seconds of EEG signal), both with fixed goals and
      goals freely chosen by the users. 

PMID- 24110923
TI  - Using frequency-domain features for the generalization of EEG error-related
      potentials among different tasks.
AB  - EEG brain-computer interfaces (BCI) require a calibration phase prior to the on
      line control of the device, which is a difficulty for the practical development
      of this technology as it is user-, session- and task-specific. The large body of
      research in BCIs based on event-related potentials (ERP) use temporal features,
      which have demonstrated to be stable for each user along time, but do not
      generalize well among tasks different from the calibration task. This paper
      explores the use of low frequency features to improve the generalization
      capabilities of the BCIs using error-potentials. The results show that there
      exists a stable pattern in the frequency domain that allows a classifier to
      generalize among the tasks. Furthermore, the study also shows that it is possible
      to combine temporal and frequency features to obtain the best of both domains.

PMID- 24110924
TI  - An online BCI game based on the decoding of users' attention to color stimulus.
AB  - Studies have shown that statistically there are differences in theta, alpha and
      beta band powers when people look at blue and red colors. In this paper, a game
      has been developed to test whether these statistical differences are good enough
      for online Brain Computer Interface (BCI) application. We implemented a two
      choice BCI game in which the subject makes the choice by looking at a color
      option and our system decodes the subject's intention by analyzing the EEG
      signal. In our system, band power features of the EEG data were used to train a
      support vector machine (SVM) classification model. An online mechanism was
      adopted to update the classification model during the training stage to account
      for individual differences. Our results showed that an accuracy of 70%-80% could
      be achieved and it provided evidence for the possibility in applying color
      stimuli to BCI applications. 

PMID- 24110925
TI  - Developing stimulus presentation on mobile devices for a truly portable SSVEP
      based BCI.
AB  - This study integrates visual stimulus presentation and near real-time data
      processing on a mobile device (e.g. a Tablet or a cell-phone) to implement a
      steady-state visual evoked potentials (SSVEP)-based brain-computer interface
      (BCI). The goal of this study is to increase the practicability, portability and
      ubiquity of an SSVEP-based BCI for daily use. The accuracy of flickering
      frequencies on the mobile SSVEP BCI system was tested against that on a
      laptop/desktop used in our previous studies. This study then analyzed the power
      spectrum density of the electroencephalogram signals elicited by the visual
      stimuli rendered on the mobile BCIs. Finally, this study performed an online test
      with the Tablet-based BCI system and obtained an averaged information transfer
      rate of 33.87 bits/min in three subjects. The current integration leads to a
      truly practical and ubiquitous SSVEP BCI on mobile devices for real-life
      applications. 

PMID- 24110926
TI  - Fast neuromorphic sound localization for binaural hearing aids.
AB  - We report on the neuromorphic sound localization circuit which can enhance the
      perceptual sensation in a hearing aid system. All elements are simple leaky
      integrate-and-fire neuron circuits with different parameters optimized to
      suppress the impacts of synaptic circuit noises. The detection range and
      resolution of the proposed neuromorphic circuit are 500 us and 5 us,
      respectively. Our results show that, the proposed technique can localize a sound
      pulse with extremely narrow duration (~ 1 ms) resulting in real-time response. 

PMID- 24110928
TI  - Enhancing scene structure in prosthetic vision using iso-disparity contour
      perturbance maps.
AB  - We present a novel approach for enhancing structurally significant features in a
      scene to facilitate safe mobility with prosthetic vision. Previous approaches
      rely on visually salient features (e.g., intensity gradients, size, texture), or
      surface fitting (e.g., ground plane extraction), to determine and convey regions
      of structural change in the scene. Such approaches can be costly to compute,
      and/or are not guaranteed to detect all features relevant to the needs of safe
      mobility (e.g., small, low-contrast trip hazards). Assuming a dense disparity
      image, we propose a novel feature using iso-disparity contours. Regions of
      significant structural change are detected via a cost function based on local
      comparisons of iso-disparity contour orientations. Through this, structurally
      interesting features such as surface boundaries and general clutter are extracted
      and emphasised in the output visual representation. Our approach is real-time,
      and requires no surface fitting. Experimental results quantitatively and
      qualitatively validate our approach. 

PMID- 24110929
TI  - Real-time dual-microphone noise classification for environment-adaptive pipelines
      of cochlear implants.
AB  - This paper presents an improved noise classification in environment-adaptive
      speech processing pipelines of cochlear implants. This improvement is achieved by
      using a dual-microphone and by using a computationally efficient feature-level
      combination approach to achieve real-time operation. A new measure named
      Suppression Advantage is also defined in order to quantify the noise suppression
      improvement of an entire pipeline due to noise classification. The noise
      classification and suppression improvement results are presented for four
      commonly encountered noise environments. 

PMID- 24110930
TI  - Influence of blood vessel conductivity in cochlear implant stimulation using a
      finite element head model.
AB  - It is known that the inclusion of blood vessels in finite element (FE) models can
      influence the current conduction results. However, there have been no studies
      exploring the impact of blood vessel conductivity on human head models for
      cochlear implant (CI) stimulation. The three-dimensional (3D) FE model presented
      in this paper aims to provide understanding in this regard. The electrical
      conductivity of blood was varied to determine the sensitivity of the 3D model.
      The results show that some of the current is exiting the cochlea and taking the
      jugular vein pathway. When compared to the case with blood vessels being omitted,
      the current density in the blood increased by 13.1%, 17.2% and 20.7% for low,
      medium and high electrical conductivity cases considered, respectively. This
      study suggests that blood vessels cannot be neglected from CI models as the
      jugular vein can provide a low impedance pathway, through which current can leave
      the cochlea. It also indicates the importance of using correct tissue property
      values for performing accurate bioelectric modeling analyses. 

PMID- 24110931
TI  - Advancements in fabrication process of microelectrode array for a retinal
      prosthesis using Liquid Crystal Polymer (LCP).
AB  - Liquid Crystal Polymer (LCP) has been considered as an alternative biomaterial
      for implantable biomedical devices primarily for its low moisture absorption rate
      compared with conventional polymers such as polyimide, parylene and silicone
      elastomers. A novel retinal prosthetic device based on monolithic encapsulation
      of LCP is being developed in which entire neural stimulation circuitries are
      integrated into a thin and eye-conformable structure. Micromachining techniques
      for fabrication of a LCP retinal electrode array have been previously reported.
      In this research, however, for being used as a part of the LCP-based retinal
      implant, we developed advanced fabrication process of LCP retinal electrode
      through new approaches such as electroplating and laser-machining in order to
      achieve higher mechanical robustness, long-term reliability and flexibility.
      Thickened metal tracks could contribute to higher mechanical strength as well as
      higher long-term reliability when combined with laser-ablation process by
      allowing high-pressure lamination. Laser-thinning technique could improve the
      flexibility of LCP electrode. 

PMID- 24110932
TI  - Magnetic control of potential microrobotic drug delivery systems: nanoparticles,
      magnetotactic bacteria and self-propelled microjets.
AB  - Development of targeted drug delivery systems using magnetic microrobots
      increases the therapeutic indices of drugs. These systems have to be incorporated
      with precise motion controllers. We demonstrate closed-loop motion control of
      microrobots under the influence of controlled magnetic fields. Point-to-point
      motion control of a cluster of iron oxide nanoparticles (diameter of 250 nm) is
      achieved by pulling the cluster towards a reference position using magnetic field
      gradients. Magnetotactic bacterium (MTB) is controlled by orienting the magnetic
      fields towards a reference position. MTB with membrane length of 5 um moves
      towards the reference position using the propulsion force generated by its
      flagella. Similarly, self-propelled microjet with length of 50 um is controlled
      by directing the microjet towards a reference position by external magnetic
      torque. The microjet moves along the field lines using the thrust force generated
      by the ejecting oxygen bubbles from one of its ends. Our control system positions
      the cluster of nanoparticles, an MTB and a microjet at an average velocity of 190
      um/s, 28 um/s, 90 um/s and within an average region-of-convergence of 132 um, 40
      um, 235 um, respectively.

PMID- 24110933
TI  - Bubble-driven light-absorbing hydrogel microrobot for the assembly of bio
      objects.
AB  - Microrobots made of light-absorbing hydrogel material were actuated by optically
      induced thermocapillary flow and move at up to 700 um/s. The micro-assembly
      capabilities of the microrobots were demonstrated by assembling polystyrene beads
      and yeast cells into various patterns on standard glass microscope slides. Two
      microrobots operating independently in parallel were also used to assemble micro
      hydrogel structures.

PMID- 24110934
TI  - A biomimetic framework for coordinating and controlling whole body movements in
      humanoid robots.
AB  - An integrated model for the coordination of whole body movements of a humanoid
      robot with a compliant ankle similar to the human case is described. It includes
      a synergy formation part, which takes into account the motor redundancy of the
      body model, and an intermittent controller, which stabilizes in a robust way
      postural sway movements, thus combining the hip strategy with ankle strategy. 

PMID- 24110935
TI  - Development of a system to provide different fields of view to eyes with a
      function to generate rapid movements.
AB  - We developed a system that provides a human user with the artificial oculomotor
      ability to control their eyes independently, which was named Virtual Chameleon
      after Chameleons. Virtual Chameleon consists of two independently controlled CCD
      cameras, a 3D tracking sensor system and a head-mounted display. The Virtual
      Chameleon control independently postures of two cameras to follow the sensors of
      the 3D tracking system smoothly. The successful users of the system were able to
      actively control visual axes by manipulating 3D sensors held by their both hands,
      to watch independent view fields presented to the left and right eyes, and to
      look around as chameleons do. Although it is thought that those independent
      fields of view the user of Virtual Chameleon corresponds to smooth movements on
      human eye movements, the system did not have functions to control angles of
      cameras rapidly in way corresponding to saccadic eye movements and compensatory
      movements as numerous animals including human do. In this paper, we implemented
      functions to control angles camera rapidly corresponding to saccadic eye
      movements in Virtual Chameleon, and we performed fundamental experiments to
      evaluate effects on the user's visual capabilities. 

PMID- 24110936
TI  - Ratbot automatic navigation by electrical reward stimulation based on distance
      measurement in unknown environments.
AB  - Traditional automatic navigation methods for bio-robots are constrained to
      configured environments and thus can't be applied to tasks in unknown
      environments. With no consideration of bio-robot's own innate living ability and
      treating bio-robots in the same way as mechanical robots, those methods neglect
      the intelligence behavior of animals. This paper proposes a novel ratbot
      automatic navigation method in unknown environments using only reward stimulation
      and distance measurement. By utilizing rat's habit of thigmotaxis and its reward
      seeking behavior, this method is able to incorporate rat's intrinsic intelligence
      of obstacle avoidance and path searching into navigation. Experiment results show
      that this method works robustly and can successfully navigate the ratbot to a
      target in the unknown environment. This work might put a solid base for
      application of ratbots and also has significant implication of automatic
      navigation for other bio-robots as well. 

PMID- 24110937
TI  - An augmented magnetic navigation system for Transcatheter Aortic Valve
      Implantation.
AB  - This research proposes an augmented magnetic navigation system for Transcatheter
      Aortic Valve Implantation (TAVI) employing a magnetic tracking system (MTS)
      combined with a dynamic aortic model and intra-operative ultrasound (US) images.
      The dynamic 3D aortic model is constructed based on the preoperative 4D computed
      tomography (CT), which is animated according to the real time electrocardiograph
      (ECG) input of patient. And a preoperative planning is performed to determine the
      target position of the aortic valve prosthesis. The temporal alignment is
      performed to synchronize the ECG signals, intra-operative US image and tracking
      information. Afterwards, with the assistance of synchronized ECG signals, the
      contour of aortic root automatic extracted from short axis US image is registered
      to the dynamic aortic model by a feature based registration intra-operatively.
      Then the augmented MTS guides the interventionist to confidently position and
      deploy the aortic valve prosthesis to target. The system was validated by animal
      studies on three porcine subjects, the deployment and tilting errors of which are
      3.17 +/- 0.91 mm and 7.40 +/- 2.89 degrees  respectively.

PMID- 24110938
TI  - An impedance-guided intra arterial catheter.
AB  - Under certain circumstances, the placement of arterial catheters can be
      difficult. In these instances, a form of guidance is preferred to avoid repeated
      insertions of the arterial catheter. Ultrasonic guidance is generally used in
      these instances, but the equipment required is expensive and cumbersome. This
      study produced an arterial catheter that is guided by the impedance of biological
      tissue encountered between the patient's skin and the lumen of the artery, with
      the aim of producing a cheaper and manageable alternative to ultrasonic guidance.
      Additionally, this study has inspected the impedance of human tissue in order to
      determine whether or not a sufficient and discernable difference between the
      impedance of the different tissue types could be identified and thus be used to
      guide an arterial catheter based on said impedance differences. The results
      indicate that the difference between subcutaneous tissue, fat tissue and skeletal
      muscle tissue are not clear enough to make accurate discrimination between tissue
      types. However, the study shows a clear difference between the impedance of
      arterial blood and the aforementioned tissue, allowing for the device to
      determine when accurate placement has been achieved. From the results obtained in
      the studies, the discrimination between blood and other intermediary tissue can
      be made with 99,4% confidence. 

PMID- 24110939
TI  - A surgical navigation system for aortic vascular surgery: a practical approach.
AB  - In aortic vascular surgery, a navigation system must represent the anatomical map
      of individual patient in order to detect the important artery. To provide a
      proper fit for positions along the dorsoventral axis, the spinous process was
      added to a currently used anatomical point set consisting of four anterior body
      landmarks. In addition, we attempted to reduce the registration error by
      compensating for alignment errors resulting from variations in tissue thickness
      at each landmark. The alignment values were examined using a human phantom
      consisting of a skeleton model with subcutaneous tissue in the semilateral
      position. Using this method, a phantom simulation and five clinical trials were
      performed. Target errors were evaluated at the orifice of the intercostal artery.
      In the phantom simulation, the error at the target point was 4.1 +/- 2.7 mm.
      However, for one patient undergoing thoracoabdominal aortic aneurysm replacement
      surgery, the target error was 8.0 mm using the proposed method. 

PMID- 24110940
TI  - A new production method of elastic silicone carotid phantom based on MRI
      acquisition using rapid prototyping technique.
AB  - In vitro experimental simulations of blood fluid in carotid artery require ideal
      phantoms that are as precise as possible. The purpose of this work is to
      demonstrate a method for carotid phantom fabrication by rapid prototyping
      technique (RP). By using 3D reconstructed projection of the 3D time-of-flight
      (TOF) Magnetic Resonance Imaging (MRI) sequence, a 12.5 cm multi-dimensional
      spatial structure of a carotid artery has been set up. Y-shaped and patient
      specific models have been generated respectively using silicone elastomer, which
      has a high resilience and a good tensile strength. The final patient specific
      model has internal carotid artery (ICA) with a highly spiraling siphon and an
      external carotid artery (ECA). Elastic properties of carotid walls have also been
      evaluated by Young's elastic modulus test and dynamic behaviors in optical and
      echography simulation experiments.

PMID- 24110941
TI  - An artificial model for studying fluid dynamics in the obstructed and stented
      ureter.
AB  - Fluid dynamics in the obstructed and stented ureter represents a non-trivial
      subject of investigation since, after stent placement, the urine can flow either
      through the stent lumen or in the extra-luminal space located between the stent
      wall and the ureteric inner wall. Fluid dynamic investigations can help
      understanding the phenomena behind stent failure (e.g. stent occlusions due to
      bacterial colonization and encrustations), which may cause kidney damage due to
      the associated high pressures generated in the renal pelvis. In this work a
      microfluidic-based transparent device (ureter model, UM) has been developed to
      simulate the fluid dynamic environment in a stented ureter. UM geometry has been
      designed from measurements on pig ureters. Pressure in the renal pelvis
      compartment has been measured against three variables: fluid viscosity (MU),
      volumetric flow rate (Q) and level of obstruction (OB%). The measurements allowed
      a quantification of the critical combination of MU, Q and OB% values which may
      lead to critical pressure levels in the kidney. Moreover, an example showing the
      possibility of applying particle image velocimetry (PIV) technology to the
      developed microfluidic device is provided.

PMID- 24110942
TI  - FES-cycling training in spinal cord injured patients.
AB  - Among the objectives of spinal cord injury (SCI) rehabilitation, (i) prevention
      of bony, muscular and joint trophism and (ii) limitation of spastic hypertone
      represent important goals to be achieved. The aim of this study is to use
      functional electrical stimulation (FES) to activate pedaling on cycle-ergometer
      and analyse effects of this technique for a rehabilitation training in SCI
      persons. Five spinal cord injured subjects were recruited and underwent a two
      months FES-cycling training. Our results show an increase of thigh muscular area
      and endurance after the FES-cycling training, without any increase of spasticity.
      This approach, which is being validated on a larger pool of patients, represents
      a potential tool for improving the rehabilitation outcome of complete and
      incomplete SCI persons.

PMID- 24110943
TI  - Electrical safety of conducted electrical weapons relative to requirements of
      relevant electrical standards.
AB  - INTRODUCTION: TASER((r)) conducted electrical weapons (CEW) deliver electrical
      pulses that can inhibit a person's neuromuscular control or temporarily
      incapacitate. TASER X26, X26P, and X2 are among CEW models most frequently
      deployed by law enforcement agencies. The X2 CEW uses two cartridge bays while
      the X26 and X26P CEWs have only one. The TASER X26P CEW electronic output circuit
      design is equivalent to that of any one of the two TASER X2 outputs. The goal of
      this paper was to analyze the nominal electrical outputs of TASER X26, X26P, and
      X2 CEWs in reference to provisions of several international standards that
      specify safety requirements for electrical medical devices and electrical fences.
      Although these standards do not specifically mention CEWs, they are the closest
      electrical safety standards and hence give very relevant guidance. METHODS: The
      outputs of two TASER X26 and two TASER X2 CEWs were measured and confirmed
      against manufacturer and other published specifications. The TASER X26, X26P, and
      X2 CEWs electrical output parameters were reviewed against relevant safety
      requirements of UL 69, IEC 60335-2-76 Ed 2.1, IEC 60479-1, IEC 60479-2, AS/NZS
      60479.1, AS/NZS 60479.2 and IEC 60601-1. Prior reports on similar topics were
      reviewed as well. RESULTS AND CONCLUSION: Our measurements and analyses confirmed
      that the nominal electrical outputs of TASER X26, X26P and X2 CEWs lie within
      safety bounds specified by relevant requirements of the above standards.

PMID- 24110944
TI  - Modulation of cortical synchrony by vagus nerve stimulation in adult rats.
AB  - Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy.
      Therapeutic mechanisms of VNS have not been elucidated. In this study, we
      measured the local field potential (LFP) with high-spatial resolution using a
      microelectrode array in adult rats, and analyzed VNS-evoked phase modulation at a
      local network level. Eight adult Wistar rats (270 - 330 g) were used. Each rat
      underwent implantation of VNS system (Cyberonics, Houston, TX., USA) under 1.5%
      isoflurane anesthesia. One week after implantation, right temporal craniotomy was
      performed under the same as previous anesthesia. Subsequently, a microelectrode
      array was placed in the temporal lobe cortex, and LFP was recorded with sampling
      rate of 1000 Hz. Phase-locking value (PLV) between all pairs of electrodes in
      varied frequency bands was calculated in order to evaluate the effect of VNS in
      terms of synchrony of neuronal activities. PLV was calculated both in a normal
      state and in an epileptic state induced by kainic acid. VNS increased PLV in a
      normal state, particularly in high-gamma band. In an epileptic state, VNS
      increased PLV in high-gamma band, and decreased in d and low-beta bands. VNS
      modulates synchrony in a band-specific and state-dependent manner. VNS might keep
      cortical synchrony within the optimal state. 

PMID- 24110945
TI  - A custom robot for Transcranial Magnetic Stimulation: first assessment on healthy
      subjects.
AB  - In this paper, a custom robotic system for Transcranial Magnetic Stimulation is
      assessed in clinical conditions on healthy subjects. A motor cortex mapping is
      performed using the robotic system with comparison to a manual approach using a
      neuronavigation system. Stimulation accuracy, repeatability are evaluated as well
      as the feeling of the system operator and the subject in terms of comfort,
      tiredness, stress level, ease-of-use. Very encouraging results are obtained on
      all these aspects, which strengthens the idea of developing robotic assistance
      for TMS. 

PMID- 24110946
TI  - Safety system for moving coil pressure algometer.
AB  - The threat of safety failure during use of potent actuators is a known problem.
      The use of such actuators in the field of pressure algometry requires adaptation
      of safety measures since stimulation is applied to human beings. This design
      provides an additional safety level required in the field of computer-controlled
      pressure algometry but in principle its usage is not restricted just to this
      area. The fuse consists of four parts (inner cylinder, outer cylinder lid, outer
      cylinder guide, and the gauge screw) which are simple and cheap to manufacture,
      easy to reassemble once the fuse has been triggered, and gaugeable with
      commercially available tools. The prototype showed acceptable levels of
      performance given the intended usage of the stimulation setup, namely increasing
      and repeated musculoskeletal stimulation. Repeatable range of holding force has
      been attained for the particular application against a rubber mat surface
      mimicking musculoskeletal tissue (96% for forces F < 20 kg, and 30% for forces 25
      kg < F <= 35 kg).

PMID- 24110947
TI  - Real-time cardiorespiratory coherence is blind to changes in respiration during
      general anesthesia.
AB  - PURPOSE: A novel real-time cardiorespiratory coherence (CRC) algorithm has been
      developed to monitor nociception during general anesthesia. CRC uses custom
      designed filters to track and analyze the respiratory sinus arrhythmia (RSA) as
      it moves in time and frequency. CRC is a form of sensor fusion between heart rate
      and respiration, estimating the strength of linear coupling between the two
      signals. The aim of this study was to estimate the effect of changes in
      respiration rate (RR) and peak airway pressure (PPaw) on CRC. The response of CRC
      was compared to a prior offline wavelet-based algorithm (WTCRC) as well as
      traditional univariate heart rate variability (HRV) measures. A nociception index
      was created for each algorithm, ranging from 0 (no nociception) to 100 (strong
      nociception). METHODS: Following ethics approval and informed consent, data were
      collected from 48 children receiving general anesthesia during dental surgery.
      The times of change in RR and PPaw events were noted in real-time. A total of 43
      RR and 35 PPaw change events were analyzed post hoc in pseudo real-time. The
      nociception index averages were compared between a baseline period and a response
      period around each event. A Wilcoxon rank-sum test was used to compare changes.
      RESULTS: The change in RR changed the CRC nociception index by an average of -2.2
      [95% CI from -10 to 4.7] (P > 0.3), and the change in PPaw changed the CRC
      nociception index by an average of 5.4 [-1.0 to 11] (P > 0.1). The changes were
      smaller than those of many traditional HRV measures. CONCLUSIONS: Real-time CRC
      was blind to the changes in respiration, and was less sensitive than many of the
      traditional HRV measures. A nociception index based on CRC can thus function
      across a wider range of respiratory conditions than can many traditional
      univariate HRV measures. The real-time CRC algorithm shows promise for monitoring
      nociception during general anesthesia.

PMID- 24110948
TI  - Very low frequency modulation in QRS slopes and its relation with respiration and
      heart rate variability during hemodialysis.
AB  - In this work, we study the very low frequency (VLF) modulation (range 0.01-0.03
      Hz) in QRS slopes, heart rate variability (HRV) and ECG-derived respiration in
      hemodialysis patients. First, the relation between QRS slopes and HRV in the VLF
      band is measured using ordinary coherence. Then, partial coherence is used to
      measure the former relationship once the effect related to respiration is
      removed. Ordinary coherence values above a statistical threshold revealed linear
      relationship between VLF modulation in QRS slopes and HRV in about 10% of
      analyzed segments, with mean +/- SD values of 0.79 +/- 0.07 for upward slope and
      0.77 +/- 0.06 for downward slope. For these segments, partial coherence values
      drop below the threshold for 64% of the cases for upward slope and 76% for
      downward slope, suggesting that the origin of the VLF modulation in QRS slopes is
      mainly driven by respiration or linearly related to it. In the rest of the cases,
      partial coherence values dropped with respect to ordinary coherence from 0.89 to
      0.77 for upward slope and from 0.86 to 0.75 for downward slope, suggesting that
      other ANS effects non-linearly related to respiration also contribute to the VLF
      modulation in QRS slopes. 

PMID- 24110949
TI  - The cortical and sub-cortical network of sensory evoked response in healthy
      subjects.
AB  - The aim of this study was to find the cortical and sub-cortical network
      responsible for the sensory evoked coherence in healthy subjects during
      electrical stimulation of right median nerve at wrist. The multitaper method was
      used to estimate the power and coherence spectrum followed by the source analysis
      method dynamic imaging of coherent sources (DICS) to find the highest coherent
      source for the basic frequency 3 Hz and the complete cortical and sub-cortical
      network responsible for the sensory evoked coherence in healthy subjects. The
      highest coherent source for the basic frequency was in the posterior parietal
      cortex for all the subjects. The cortical and sub-cortical network comprised of
      the primary sensory motor cortex (SI), secondary sensory motor cortex (SII),
      frontal cortex and medial pulvinar nucleus in the thalamus. The cortical and sub
      cortical network responsible for the sensory evoked coherence was found
      successfully with a 64-channel EEG system. The sensory evoked coherence is
      involved with a thalamo-cortical network in healthy subjects.

PMID- 24110950
TI  - Automated detection of apnea/hypopnea events in healthy children polysomnograms:
      preliminary results.
AB  - A methodology to detect sleep apnea/hypopnea events in the respiratory signals of
      polysomnographic recordings is presented. It applies empirical mode decomposition
      (EMD), Hilbert-Huang transform (HHT), fuzzy logic and signal preprocessing
      techniques for feature extraction, expert criteria and context analysis. EMD, HHT
      and fuzzy logic are used for artifact detection and preliminary detection of
      respiration signal zones with significant variations in the amplitude of the
      signal; feature extraction, expert criteria and context analysis are used to
      characterize and validate the respiratory events. An annotated database of 30 all
      night polysomnographic recordings, acquired from 30 healthy ten-year-old
      children, was divided in a training set of 15 recordings (485 sleep
      apnea/hypopnea events), a validation set of five recordings (109 sleep
      apnea/hypopnea events), and a testing set of ten recordings (281 sleep
      apnea/hypopnea events). The overall detection performance on the testing data set
      was 89.7% sensitivity and 16.3% false-positive rate. The next step is to include
      discrimination among apneas, hypopneas and respiratory pauses. 

PMID- 24110951
TI  - Circadian changes of influence of swallowing on heart rate variability with
      respiratory-phase domain analysis.
AB  - Respiratory sinus arrhythmia (RSA) is known as an index of cardiac vagal activity
      and useful to evaluate the response of the cardiovascular system to external
      stimuli. As an external stimulation, swallowing is known to strongly affect the
      cardiovascular system. However, the influence of swallowing and its relation with
      the autonomic nervous system remain incompletely understood. In this study, since
      autonomic nervous control of the cardiovascular system has a circadian rhythm, we
      evaluated circadian changes of influence of swallowing on RSA. Measurements were
      conducted on healthy humans with periodic swallowing in the morning, afternoon,
      and evening. RSA waveforms were extracted from an instantaneous R-R Interval
      (RRI) as functions of the respiratory phase and the data were divided into three
      subsets with respiration with swallowing, one respiration after the swallowing,
      and normal respiration. As a result, the RSA amplitude during respiration with
      swallowing was larger in the morning than in the evening. In addition, the
      minimum RRI during respiration with swallowing was larger in the morning than in
      the afternoon and evening. Thus, circadian changes of influence of swallowing on
      the RSA amplitude are extracted and swallowing-induced tachycardia is different
      with different states of autonomic nervous activity. Therefore, vagal activity
      should largely contribute to tachycardia induced by swallowing and evaluation of
      circadian changes of influences of external stimuli would be useful to
      investigate the mechanisms of response of the cardiovascular system to external
      stimuli. 

PMID- 24110952
TI  - Characterization of surrogate parameters for blood pressure regulation in
      neurally-mediated syncope.
AB  - Neurally Mediated Syncope (NMS) is often cited as the most common cause of
      syncope. It can lead to severe consequences such as injuries, high rates of
      hospitalization and reduced quality of life, especially in elderly populations.
      Therefore, information about the syncope triggers and reflex mechanisms would be
      of a great value in the development of a cost-effective p-health system for the
      prediction of syncope episodes, by enhancing patients' quality of life and
      reducing the incidence of syncope related disorders/conditions. In the present
      paper we study the characterization of syncope reflex mechanisms and blood
      pressure changes from the analysis of several non-invasive modalities (ECG, ICG
      and PPG). Several parameters were extracted in order to characterize the
      chronotropic, inotropic and vascular tone changes. Thus, we evaluate the ability
      of parameters such as Heart Rate (HR), Pre-Ejection Period (PEP) and Left
      Ventricular Ejection Time (LVET) to characterize the physiological mechanisms
      behind the development of reflex syncope and their potential syncope prediction
      capability. The significant parameter changes (e.g. HR from 12.9% to -12.4%, PEP
      from 14.9% to -3.8% and LVET from -14.4% to 12.3%) found in the present work
      suggest the feasibility of these surrogates to characterize the blood pressure
      regulation mechanisms during impending syncope. 

PMID- 24110954
TI  - Application of artificial neural networks on mosquito Olfactory Receptor Neurons
      for an olfactory biosensor.
AB  - Various odorants such as carbon dioxide (CO2) and 1-octen-3-ol, underlie the host
      seeking behaviors of the major malaria vector Anopheles Gambiae. Highlighted by
      the olfactory processing strength of the mosquito, such a powerful olfactory
      sense could serve as the sensors of an artificial olfactory biosensor. In this
      work, we use the firing rates of the A. Gambiae mosquito Olfactory Receptor
      Neurons (ORNs), to train an Artificial Neural Network (ANN) for the
      classification of volatile odorants into their known chemical classes and assess
      their suitability for an olfactory biosensor. With the implementation of
      bootstrapping, a more representative result was obtained wherein we demonstrate
      the training of a hybrid ANN consisting of an array of Multi-Layer Perceptrons
      (MLPs) with optimal number of hidden neurons. The ANN system was able to
      correctly class 90.1% of the previously unseen odorants, thus demonstrating very
      strong evidence for the use of A. Gambiae olfactory receptors coupled with an ANN
      as an olfactory biosensor. 

PMID- 24110953
TI  - Combining genetic algorithm and Levenberg-Marquardt algorithm in training neural
      network for hypoglycemia detection using EEG signals.
AB  - Hypoglycemia is the most common but highly feared complication induced by the
      intensive insulin therapy in patients with type 1 diabetes mellitus (T1DM).
      Nocturnal hypoglycemia is dangerous because sleep obscures early symptoms and
      potentially leads to severe episodes which can cause seizure, coma, or even
      death. It is shown that the hypoglycemia onset induces early changes in
      electroencephalography (EEG) signals which can be detected non-invasively. In our
      research, EEG signals from five T1DM patients during an overnight clamp study
      were measured and analyzed. By applying a method of feature extraction using Fast
      Fourier Transform (FFT) and classification using neural networks, we establish
      that hypoglycemia can be detected efficiently using EEG signals from only two
      channels. This paper demonstrates that by implementing a training process of
      combining genetic algorithm and Levenberg-Marquardt algorithm, the classification
      results are improved markedly up to 75% sensitivity and 60% specificity on a
      separate testing set. 

PMID- 24110955
TI  - Bioelectric signal classification using a recurrent probabilistic neural network
      with time-series discriminant component analysis.
AB  - This paper outlines a probabilistic neural network developed on the basis of time
      series discriminant component analysis (TSDCA) that can be used to classify high
      dimensional time-series patterns. TSDCA involves the compression of high
      dimensional time series into a lower-dimensional space using a set of orthogonal
      transformations and the calculation of posterior probabilities based on a
      continuous-density hidden Markov model that incorporates a Gaussian mixture model
      expressed in the reduced-dimensional space. The analysis can be incorporated into
      a neural network so that parameters can be obtained appropriately as network
      coefficients according to backpropagation-through-time-based training algorithm.
      The network is considered to enable high-accuracy classification of high
      dimensional time-series patterns and to reduce the computation time taken for
      network training. In the experiments conducted during the study, the validity of
      the proposed network was demonstrated for EEG signals. 

PMID- 24110956
TI  - Localized Sparse Code Gradient in Alzheimer's disease staging.
AB  - The accurate diagnosis of Alzheimer's disease (AD) at different stages is
      essential to identify patients at high risk of dementia and plan prevention or
      treatment measures accordingly. In this study, we proposed a new AD staging
      method for the entire spectrum of AD including the AD, Mild Cognitive Impairment
      with and without AD conversions, and Cognitive Normal groups. Our method embedded
      the high dimensional multi-view features derived from neuroimaging data into a
      low dimensional feature space and could form a more distinctive representation
      than the naive concatenated features. It also updated the testing data based on
      the Localized Sparse Code Gradients (LSCG) to further enhance the classification.
      The LSCG algorithm, validated using Magnetic Resonance Imaging data from the ADNI
      baseline cohort, achieved significant improvements on all diagnosis groups
      compared to using the original sparse coding method. 

PMID- 24110957
TI  - A new method of concurrently visualizing states, values, and actions in
      reinforcement based brain machine interfaces.
AB  - This paper presents the first attempt to quantify the individual performance of
      the subject and of the computer agent on a closed loop Reinforcement Learning
      Brain Machine Interface (RLBMI). The distinctive feature of the RLBMI
      architecture is the co-adaptation of two systems (a BMI decoder in agent and a
      BMI user in environment). In this work, an agent implemented using Q-learning via
      kernel temporal difference (KTD)(lambda) decodes the neural states of a monkey
      and transforms them into action directions of a robotic arm. We analyze how each
      participant influences the overall performance both in successful and missed
      trials by visualizing states, corresponding action value Q, and resulting actions
      in two-dimensional space. With the proposed methodology, we can observe how the
      decoder effectively learns a good state to action mapping, and how neural states
      affect the prediction performance. 

PMID- 24110959
TI  - Cortical dipole imaging using truncated total least squares considering transfer
      matrix error.
AB  - Cortical dipole imaging has been proposed as a method to visualize
      electroencephalogram in high spatial resolution. We investigated the inverse
      technique of cortical dipole imaging using a truncated total least squares
      (TTLS). The TTLS is a regularization technique to reduce the influence from both
      the measurement noise and the transfer matrix error caused by the head model
      distortion. The estimation of the regularization parameter was also investigated
      based on L-curve. The computer simulation suggested that the estimation accuracy
      was improved by the TTLS compared with Tikhonov regularization. The proposed
      method was applied to human experimental data of visual evoked potentials. We
      confirmed the TTLS provided the high spatial resolution of cortical dipole
      imaging. 

PMID- 24110960
TI  - Cortical neural activities associated with binocular rivalry: an EEG-fMRI
      integrative study.
AB  - Binocular rivalry occurs over time when each eye is simultaneously presented with
      different visual stimuli. We have addressed which brain regions are and the
      mechanisms involved in binocular rivalry using EEG and fMRI measurements of
      cortical activities during observations of competitive (rivalry) and cooperative
      (fusion) drifting vertical gratings. By applying an EEG-fMRI integrative method,
      we analyzed the time courses of multiple cortical sources of event-related
      potentials obtained under rivalry or fusion conditions. We detected significant
      cortical activities at bilateral MT+/V5 and the right prefrontal eye field in the
      rivalry condition; however, this may not reflect intrinsic alternation in
      binocular rivalry. Our findings suggest that novel integrative methods are
      necessary to investigate the distributed cortical network associated with
      binocular rivalry, through analysis of multiple cortical sources of event-related
      desynchronization and/or synchronization in certain frequency bands. 

PMID- 24110961
TI  - Wavelet based sparse source imaging technique.
AB  - The present study proposed a novel multi-resolution wavelet to efficiently
      compress cortical current densities on the highly convoluted cortical surface.
      The basis function of the proposed wavelet is supported on triangular faces of
      the cortical mesh and it is thus named as the face-based wavelet to be
      distinguished from other vertex-based wavelets. The proposed face-based wavelet
      was used as a transform to gain the sparse representation of cortical sources and
      then was integrated into the framework of L1-norm regularizations with the
      purpose to improve the performance of sparse source imaging (SSI) in solving
      EEG/MEG inverse problems. Monte Carlo simulations were conducted with multiple
      extended sources (up to ten) at random locations. Experimental MEG data from an
      auditory induced language task was further adopted to evaluate the performance of
      the proposed wavelet based SSI technique. The present results indicated that the
      face-based wavelet can efficiently compress cortical current densities and has
      better performance than the vertex-based wavelet in helping inverse source
      reconstructions in terms of estimation accuracies in source localization and
      source extent. Experimental results further indicated improved detection
      performance of the face-based wavelet as compared with the vertex-based wavelet
      in the framework of SSI. It thus suggests the proposed wavelet based SSI can
      become a promising tool in studying brain functions and networks. 

PMID- 24110962
TI  - Differences in the perceived music pleasantness between monolateral cochlear
      implanted and normal hearing children assessed by EEG.
AB  - The perception of the music in cochlear implanted (CI) patients is an important
      aspect of their quality of life. In fact, the pleasantness of the music
      perception by such CI patients can be analyzed through a particular analysis of
      EEG rhythms. Studies on healthy subjects show that exists a particular frontal
      asymmetry of the EEG alpha rhythm which can be correlated with pleasantness of
      the perceived stimuli (approach-withdrawal theory). In particular, here we
      describe differences between EEG activities estimated in the alpha frequency band
      for a monolateral CI group of children and a normal hearing one during the
      fruition of a musical cartoon. The results of the present analysis showed that
      the alpha EEG asymmetry patterns related to the normal hearing group refers to a
      higher pleasantness perception when compared to the cerebral activity of the
      monolateral CI patients. In fact, the present results support the statement that
      a monolateral CI group could perceive the music in a less pleasant way when
      compared to normal hearing children. 

PMID- 24110963
TI  - Reference-free harmonic regression technique to remove EEG-fMRI
      ballistocardiogram artifacts.
AB  - Obtaining high quality electroencephalogram (EEG) data simultaneously with
      functional MRI (fMRI) recordings is increasingly relevant for the study of
      cognitive and clinical brain states - as EEG-fMRI offers uniquely high
      spatiotemporal resolution imaging of brain activity. However, the utility of this
      technique is limited by ballistocardiogram (BCG) artifacts induced in the EEG by
      cardiac pulsation and head movement inside the magnetic field. In this paper, we
      introduce a novel model-based harmonic regression technique to remove BCG
      artifacts from EEG recorded in the MR scanner. Our technique uses physically
      motivated parametric models of the BCG artifact and the true EEG signal, and
      incorporates maximum likelihood approaches to identify model parameters, estimate
      and subtract the BCG from corrupted EEG measurements. We show that this method
      effectively removes BCG artifacts from EEG recorded in the MR scanner, restores
      simulated oscillatory signatures and enables over 20-fold improvement in SNR in
      bands of interest. Further, unlike common BCG removal techniques that rely on
      cardiac or motion reference signals, our approach is reference-free and thus is
      useful when reference signals are corrupted or difficult to acquire. 

PMID- 24110964
TI  - Noninvasive imaging of internal muscle activities from multi-channel surface EMG
      recordings.
AB  - Surface Electromyogram (sEMG) technology provides a non-invasive way for rapid
      monitoring muscle activities, but its poor spatial resolution and specificity
      limit its application in clinic. To overcome these limitations, a noninvasive
      muscle activity imaging (MAI) approach has been developed and used to reconstruct
      internal muscle activities from multi-channel sEMG recordings. A realistic
      geometric hand model is developed from high-resolution MR images and a
      distributed bioelectric dipole source model is employed to describe the internal
      muscle activity space of the muscles. The finite element method and weighted
      minimum norm method are utilized solve the forward and inverse problems
      respectively involved in the proposed MAI technique. A series of computer
      simulations was conducted to test the performance of the proposed MAI approach.
      Results show that reconstruction results achieved by the MAI technique indeed
      provide us more detailed and dynamic information of internal muscle activities,
      which enhance our understanding of the mechanisms underlying the surface EMG
      recordings. 

PMID- 24110965
TI  - A novel tracing method for the segmentation of cell wall networks.
AB  - Cell wall networks are a common subject of research in biology, which are
      important for plant growth analysis, organ studies, etc. In order to automate the
      detection of individual cells in such cell wall networks, we propose a new
      segmentation algorithm. The proposed method is a network tracing algorithm,
      exploiting the prior knowledge of the network structure. The method is applicable
      on multiple microscopy modalities such as fluorescence, but also for images
      captured using non invasive microscopes such as differential interference
      contrast (DIC) microscopes. 

PMID- 24110966
TI  - PH2 - a dermoscopic image database for research and benchmarking.
AB  - The increasing incidence of melanoma has recently promoted the development of
      computer-aided diagnosis systems for the classification of dermoscopic images.
      Unfortunately, the performance of such systems cannot be compared since they are
      evaluated in different sets of images by their authors and there are no public
      databases available to perform a fair evaluation of multiple systems. In this
      paper, a dermoscopic image database, called PH2, is presented. The PH2 database
      includes the manual segmentation, the clinical diagnosis, and the identification
      of several dermoscopic structures, performed by expert dermatologists, in a set
      of 200 dermoscopic images. The PH2 database will be made freely available for
      research and benchmarking purposes.

PMID- 24110967
TI  - Mass segmentation in mammograms by using Bidimensional Emperical Mode
      Decomposition BEMD.
AB  - Breast mass segmentation in mammography plays a crucial role in Computer-Aided
      Diagnosis (CAD) systems. In this paper a Bidimensional Emperical Mode
      Decomposition (BEMD) method is introduced for the mass segmentation in
      mammography images. This method is used to decompose images into a set of
      functions named Bidimensional Intrinsic Mode Functions (BIMF) and a residue. Our
      approach consists of three steps: 1) the regions of interest (ROIs) were
      identified by using iterative thresholding; 2) the contour of the regions of
      interest (ROI) was extracted from the first BIMF by using the (BEMD) method; 3)
      the region of interest was finally refined by the extracted contour. The proposed
      approach is tested on (MIAS) database and the obtained results demonstrate the
      efficacy of the proposed approach. 

PMID- 24110968
TI  - Segmenting overlapping cell nuclei in digital histopathology images.
AB  - Automatic quantification of cell nuclei in immunostained images is highly desired
      by pathologists in diagnosis. In this paper, we present a new approach for the
      segmentation of severely clustered overlapping nuclei. The proposed approach
      first involves applying a combined global and local threshold method to extract
      foreground regions. In order to segment clustered overlapping nuclei in the
      foreground regions, seed markers are obtained by utilizing morphological
      filtering and intensity based region growing. Seeded watershed is then applied
      and clustered nuclei are separated. As pixels corresponding to stained cellular
      cytoplasm can be falsely identified as belonging to nuclei, a post processing
      step identifying positive nuclei pixels is added to eliminate these false pixels.
      This new approach has been tested on a set of manually labeled Tissue Microarray
      (TMA) and Whole Slide Images (WSI) colorectal cancers stained for the biomarker
      P53. Experimental results show that it outperformed currently available state of
      the art methods in nuclei segmentation. 

PMID- 24110970
TI  - Cellular automata and anisotropic diffusion filter based interactive tumor
      segmentation for positron emission tomography.
AB  - Tumor segmentation in positron emission tomography (PET) aids clinical diagnosis
      and in assessing treatment response. However, the low resolution and signal-to
      noise inherent in PET images, makes accurate tumor segmentation challenging.
      Manual delineation is time-consuming and subjective, whereas fully automated
      algorithms are often limited to particular tumor types, and have difficulties in
      segmenting small and low-contrast tumors. Interactive segmentation may reduce the
      inter-observer variability and minimize the user input. In this study, we present
      a new interactive PET tumor segmentation method based on cellular automata (CA)
      and a nonlinear anisotropic diffusion filter (ADF). CA is tolerant of noise and
      image pattern complexity while ADF reduces noise while preserving edges. By
      coupling CA with ADF, our proposed approach was robust and accurate in detecting
      and segmenting noisy tumors. We evaluated our method with computer simulation and
      clinical data and it outperformed other common interactive PET segmentation
      algorithms. 

PMID- 24110971
TI  - Classification of diffuse lung diseases patterns by a sparse representation based
      method on HRCT images.
AB  - This paper describes a computer-aided diagnosis (CAD) method to classify diffuse
      lung diseases (DLD) patterns on HRCT images. Due to the high variety and
      complexity of DLD patterns, the performance of conventional methods on
      recognizing DLD patterns featured by geometrical information is limited. In this
      paper, we introduced a sparse representation based method to classify normal
      tissues and five types of DLD patterns including consolidation, ground-glass
      opacity, honeycombing, emphysema and nodular. Both CT values and eigenvalues of
      Hessian matrices were adopted to calculate local features. The 2360 VOIs from 117
      subjects were separated into two independent set. One set was used to optimize
      parameters, and the other set was adopted to evaluation. The proposed technique
      has a overall accuracy of 95.4%. Experimental results show that our method would
      be useful to classify DLD patterns on HRCT images. 

PMID- 24110972
TI  - Overlapping node discovery for improving classification of lung nodules.
AB  - Distinguishing malignant lung nodules from benign nodules is an important aspect
      of lung cancer diagnosis. In this paper, we propose an automatic method to
      classify lung nodules into four different types, i.e. well-circumscribed, juxta
      vascular, juxta-pleural and pleural-tail. Additionally, since the morphology of
      lung nodules forms a continuum between the different types, our proposed method
      is superior to previous methods that classify single nodules into a single type.
      First, a weighted similarity network is constructed based on the SVM with
      probability estimates, turning the 128-length SIFT descriptor to a 4-length
      probability vector against the four types. Then, the classification of nodules
      while identifying those with overlapping types is made using the weighed Clique
      Percolation Method (CPMw). We evaluate the proposed method on low-dose CT images
      from ELCAP. Our results show that there is more overlap between well
      circumscribed and juxta-vascular, and between juxta-pleural and pleural tail.
      Also, quantitative comparisons among various methods demonstrate highly effective
      nodule classification results by identifying the overlapping nodule types. 

PMID- 24110973
TI  - Semantic characteristics prediction of pulmonary nodule using Artificial Neural
      Networks.
AB  - Since it is difficult to choose which computer calculated features are effective
      to predict the malignancy of pulmonary nodules, in this study, we add a semantic
      level of Artificial Neural Networks (ANNs) structure to improve intuition of
      features selection. The works of this study include two: 1) seeking the
      relationships between computer-calculated features and medical semantic concepts
      which could be understood by human; 2) providing an objective assessment method
      to predict the malignancy from semantic characteristics. We used 60 thoracic CT
      scans collected from the Lung Image Database Consortium (LIDC) database, in which
      the suspicious lesions had been delineated and annotated by 4 radiologists
      independently. Corresponding to the two works of this study, correlation analysis
      experiment and agreement experiment were performed separately. 

PMID- 24110974
TI  - Femoral cartilage segmentation in knee MRI scans using two stage voxel
      classification.
AB  - Using more than one classification stage and exploiting class population
      imbalance allows for incorporating powerful classifiers in tasks requiring large
      scale training data, even if these classifiers scale badly with the number of
      training samples. This led us to propose a two-stage classifier for segmenting
      tibial cartilage in knee MRI scans combining nearest neighbor classification and
      support vector machines (SVMs). Here we apply it to femoral cartilage
      segmentation. We describe the similarities and differences between segmenting
      these two knee cartilages. For further speeding up batch SVM training, we propose
      loosening the stopping condition in the quadratic program solver before
      considering moving on to other approximation techniques such as online SVMs. The
      two-stage approach reached a higher accuracy in comparison to the one-stage state
      of-the-art method. It also achieved better inter-scan segmentation
      reproducibility when compared to a radiologist as well as the current state-of
      the-art method. 

PMID- 24110975
TI  - Scleroderma capillary pattern identification using texture descriptors and
      ensemble classification.
AB  - Various connective tissue diseases lead to morphological alternations of blood
      capillaries. Consequently, observation of the capillaries at the finger nailfold 
      nailfold capillaroscopy (NC) - is a standard method for diagnosing diseases such
      as scleroderma or Raynaud's phenomenon. This is typically performed through
      manual inspection by an expert to lead to a determination of one of the
      established NC scleroderma patterns (early, active, and late). In this paper, we
      present an automated method of analysing nailfold capillaroscopy images and
      categorising them into NC patterns. For this purpose, we extract a carefully
      chosen set of texture features from the images and employ an ensemble
      classification approach to arrive at decisions for each captured finger which are
      then aggregated to form a diagnosis for the patient. Experimental results on a
      set of 60 NC images from 16 subjects demonstrate the accuracy and usefulness of
      our presented approach. 

PMID- 24110976
TI  - A modified anomaly detection method for capsule endoscopy images using non-linear
      color conversion and Higher-order Local Auto-Correlation (HLAC).
AB  - Capsule endoscopy is a patient-friendly endoscopy broadly utilized in
      gastrointestinal examination. However, the efficacy of diagnosis is restricted by
      the large quantity of images. This paper presents a modified anomaly detection
      method, by which both known and unknown anomalies in capsule endoscopy images of
      small intestine are expected to be detected. To achieve this goal, this paper
      introduces feature extraction using a non-linear color conversion and Higher
      order Local Auto Correlation (HLAC) Features, and makes use of image partition
      and subspace method for anomaly detection. Experiments are implemented among
      several major anomalies with combinations of proposed techniques. As the result,
      the proposed method achieved 91.7% and 100% detection accuracy for swelling and
      bleeding respectively, so that the effectiveness of proposed method is
      demonstrated.

PMID- 24110977
TI  - Microwave breast tumor detection and size estimation using contrast-agent-loaded
      magnetotactic bacteria.
AB  - We propose a new approach to microwave breast tumor detection based on the use of
      bio-compatible flagellated magnetotactic bacteria (MTB). Previous work has shown
      that the directions and speeds of these bacterial microrobots adapted to operate
      in human microvasculature can be guided along preplanned paths deep inside the
      human body through external magnetic fields. Furthermore, a microwave contrast
      agent can be loaded onto MTB to alter the dielectric properties of tissues near
      the agent. Based on these two phenomena, we illustrate how multiple
      agglomerations of MTB released into human breast could be tracked simultaneously
      and monitored using differential microwave imaging (DMI) techniques. We also
      present novel strategies to detect and localize a breast cancerous mass as well
      as estimate its size through this new DMI-trackable bacterial propulsion and
      steering approach, and use an anatomically realistic breast model as a testbed to
      verify the feasibility of this breast cancer diagnostic technique. 

PMID- 24110978
TI  - Characteristics of magnetic probes for identifying sentinel lymph nodes.
AB  - The identification of the sentinel lymph nodes that cause tumor metastasis is
      important in breast cancer therapy. The detection of magnetic fluid accumulating
      in the lymph nodes using a magnetic probe allows surgeons to identify the lymph
      nodes. In this study, we carried out numerical simulations and experiments to
      investigate the sensitivity and basic characteristics of a magnetic probe
      consisting of a permanent magnet and a small magnetic sensor. The measured
      magnetic flux density arising from the magnetic fluid agreed well with the
      numerical results. In addition, the results helped realize an appropriate probe
      configuration for achieving high sensitivity to magnetic fluid. A prototype probe
      detected magnetic fluid located 30 mm from the probe head. 

PMID- 24110979
TI  - An RFID tag system-on-chip with wireless ECG monitoring for intelligent
      healthcare systems.
AB  - This paper presents a low-power wireless ECG acquisition system-on-chip (SoC),
      including an RF front-end circuit, a power unit, an analog front-end circuit, and
      a digital circuitry. The proposed RF front-end circuit can provide the amplitude
      shift keying demodulation and distance to digital conversion to accurately
      receive the data from the reader. The received data will wake up the power unit
      to provide the required supply voltages of analog front-end (AFE) and digital
      circuitry. The AFE, including a pre-amplifier, an analog filter, a post
      amplifier, and an analog-to-digital converter, is used for the ECG acquisition.
      Moreover, the EPC Class I Gen 2 UHF standard is employed in the digital circuitry
      for the handshaking of communication and the control of the system. The proposed
      SoC has been implemented in 0.18-um standard CMOS process and the measured
      results reveal the communication is compatible to the RFID protocol. The average
      power consumption for the operating chip is 12 uW. Using a Sony PR44 battery to
      the supply power (605mAh@1.4V), the RFID tag SoC operates continuously for about
      50,000 hours (>5 years), which is appropriate for wireless wearable ECG
      monitoring systems. 

PMID- 24110980
TI  - Validation of a wrist monitor for accurate estimation of RR intervals during
      sleep.
AB  - While the incidence of sleep disorders is continuously increasing in western
      societies, there is a clear demand for technologies to asses sleep-related
      parameters in ambulatory scenarios. The present study introduces a novel concept
      of accurate sensor to measure RR intervals via the analysis of photo
      plethysmographic signals recorded at the wrist. In a cohort of 26 subjects
      undergoing full night polysomnography, the wrist device provided RR interval
      estimates in agreement with RR intervals as measured from standard
      electrocardiographic time series. The study showed an overall agreement between
      both approaches of 0.05 +/- 18 ms. The novel wrist sensor opens the door towards
      a new generation of comfortable and easy-to-use sleep monitors. 

PMID- 24110981
TI  - Clock recovery PLL with gated PFD for NRZ ON-OFF Modulated Signals in a retinal
      implant system.
AB  - A Clock Recovery Phase Locked Loop with Gated Phase Frequency Detector (GPLL) for
      NRZ ON-OFF Modulated Signals with low data transmission rates for an inductively
      powered subretinal implant system is presented. Low data transmission rate leads
      to a long absence of inductive powering in the system when zeros are transmitted.
      Consequently there is no possibility to extract any clock in these pauses, thus
      the digital circuitry can not work any more. Compared to a commonly used PLL for
      clock extraction, no certain amount of data transitions is needed. This is
      achieved by having two operating modes. In one mode the GPLL tracks the HF input
      signal. In the other, the GPLL is an adjustable oscillator oscillating at the
      last used frequency. The proposed GPLL is fabricated and measured using a 350 nm
      High Voltage CMOS technology.

PMID- 24110982
TI  - A CMOS UWB transmitter for possible use for medical and biological imaging based
      on radio-wave induced ultrasound.
AB  - Medical and biological imaging based on radio-wave induced ultrasound with a
      single source capable of irradiating multiple signals of different frequencies
      simultaneously can be implemented using ultra-wideband (UWB) technique.
      Development of a low-cost miniature UWB CMOS transmitter that can be used for
      this medical application is presented. The UWB transmitter designed using a 0.25
      um CMOS process can generate and transmit both monocycle pulses from 140 to 350
      ps and impulses from 100 to 300 ps which contain many concurrent frequencies such
      as 3.1-10.6 GHz of the UWB spectrum. 

PMID- 24110983
TI  - Wirelessly addressable heater array for centrifugal microfluidics and Escherichia
      coli sterilization.
AB  - Localized temperature control and heater interface remain challenges in
      centrifugal microfluidics and integrated lab-on-a-chip devices. This paper
      presents a new wireless heating method that enables selective activation of
      micropatterned resonant heaters using external radiofrequency (RF) fields and its
      applications. The wireless heaters in an array are individually activated by
      modulating the frequency of the external field. Temperature of 93  degrees C is
      achieved in the heater when resonated with a 0.49-W RF output power. The wireless
      method is demonstrated to be fully effective for heating samples under spinning
      at high speeds, showing its applicability to centrifugal systems. Selective
      sterilization of Escherichia coli through the wireless heating is also
      demonstrated. Healthcare applications with a focus on wound sterilization are
      discussed along with preliminary experiments, showing promising results. 

PMID- 24110984
TI  - Novel liquid equilibrium valving on centrifugal microfluidic CD platform.
AB  - One of the main challenges faced by researchers in the field of microfluidic
      compact disc (CD) platforms is the control of liquid movement and sequencing
      during spinning. This paper presents a novel microfluidic valve based on the
      principle of liquid equilibrium on a rotating CD. The proposed liquid equilibrium
      valve operates by balancing the pressure produced by the liquids in a source and
      a venting chamber during spinning. The valve does not require external forces or
      triggers, and is able to regulate burst frequencies with high accuracy. In this
      work, we demonstrate that the burst frequency can be significantly raised by
      making just a small adjustment of the liquid height in the vent chamber. Finally,
      the proposed valve ng method can be used separately or combined with other
      valving methods in advance microfluidic processes. 

PMID- 24110985
TI  - Multi-level 3D implementation of thermo-pneumatic pumping on centrifugal
      microfluidic CD platforms.
AB  - Thermo-pneumatic (TP) pumping is a method employing the principle of expanding
      heated air to transfer fluids back towards the CD center on the centrifugal
      microfluidic CD platform. While the TP features are easy to fabricate as no
      moving parts are involved, it consumes extra real estate on the CD, and because
      heating is involved, it introduces unnecessary heating to the fluids on the CD.
      To overcome these limitations, we introduce a multi-level 3D approach and
      implement forced convection heating. In a multi-level 3D CD, the TP features are
      relocated to a separate top level, while the microfluidic process remains on a
      lower bottom level. This allows for heat shielding of the fluids in the
      microfluidic process level, and also improve usage of space on the CD. To aid in
      future implementations of TP pumping on a multi-level 3D CD, studies on the
      effect of heat source setting, and the effect of positioning the TP feature (it
      distance from the CD center) on CD surface heating are also presented. In this
      work, we successfully demonstrate a multi-level 3D approach to implement TP
      pumping on the microfluidic CD platform. 

PMID- 24110986
TI  - Liquid-phase sample preparation method for real-time monitoring of airborne
      asbestos fibers by dual-mode high-throughput microscopy.
AB  - Asbestos that had been used widely as a construction material is a first-level
      carcinogen recognized by the World Health Organization. It can be accumulated in
      body by inhalation causing virulent respiratory diseases including lung cancer.
      In our previous study, we developed a high-throughput microscopy (HTM) system
      that can minimize human intervention accompanied by the conventional phase
      contrast microscopy (PCM) through automated counting of fibrous materials and
      thus significantly reduce analysis time and labor. Also, we attempted selective
      detection of chrysotile using DksA protein extracted from Escherichia coli
      through a recombinant protein production technique, and developed a dual-mode HTM
      (DM-HTM) by upgrading the HTM device. We demonstrated that fluorescently-labeled
      chrysotile asbestos fibers can be identified and enumerated automatically among
      other types of asbestos fibers or non-asbestos particles in a high-throughput
      manner through a newly modified HTM system for both reflection and fluorescence
      imaging. However there is a limitation to apply DM-HTM to airborne sample with
      current air collecting method due to the difficulty of applying the protein to
      dried asbestos sample. Here, we developed a technique for preparing liquid-phase
      asbestos sample using an impinger normally used to collect odor molecules in the
      air. It would be possible to improve the feasibility of the dual-mode HTM by
      integrating a sample preparation unit for making collected asbestos sample
      dispersed in a solution. The new technique developed for highly sensitive and
      automated asbestos detection can be a potential alternative to the conventional
      manual counting method, and it may be applied on site as a fast and reliable
      environmental monitoring tool. 

PMID- 24110987
TI  - A simple microfluidic gradient generator with a soft-lithographically prototyped,
      high-aspect-ratio, ~2 um wide microchannel.
AB  - We have developed a cast microfluidic chip that contains a thin (~2 um wide)
      microchannel that is smoothly connected to thick microfluidics. The thin line
      features having high aspect ratio for a low-cost photolithography in which an
      emulsion photomask was used (1:1 ~ 1:3) were fabricated by exposing SU-8
      photoresist to diffused 185 nm UV light emitted by a low-cost ozone lamp from the
      backside of the substrate to ensure sufficient crosslinking of small regions of
      the SU-8 photoresist. An H-shaped microfluidic configuration was used, in which
      the thin channel maintained constant diffusion fronts beyond purely static
      diffusion. We also demonstrated the long-term effects of a gradient of nerve
      growth factor on axon elongation by primary neurons cultured in the micro
      channel.

PMID- 24110988
TI  - Distinct patterns of cell motion inside a micro-channel under different osmotic
      conditions.
AB  - The effect of osmotic condition on a living cell inside a micro-channel is
      firstly studied in this work. By utilizing a high-speed camera, we observed
      distinct patterns of cell motion under different osmotic conditions, which are
      established by saline with different concentrations of sodium chloride (NaCl).
      The cell motions are tracked by a computer, and are presented by the coordinates
      of location and time (x-t chart). The motions of cells under hypotonic condition
      (NaCl% < 0.9%) are convex curves on the chart while the ones under isotonic and
      hypertonic conditions (NaCl% >= 0.9%) are concave curves. Since saline is widely
      used in both medical practices and cell-related researches, our results point out
      two important facts: 1) Cells are sensitive to the percentage of NaCl. One
      percent difference in overall concentration makes dramatic changes in cell
      characteristics, such as cell stiffness. 2) The micro-channel method can clearly
      tell the difference between hypotonic, isotonic and hypertonic conditions
      according to the pattern of cell motion. Interpretations of the phenomena from
      different perspectives are also discussed in this paper. 

PMID- 24110989
TI  - A versatile platform for multilevel modeling of physiological systems:
      template/instance framework for large-scale modeling and simulation.
AB  - Building multilevel models of physiological systems is a significant and
      effective method for integrating a huge amount of bio-physiological data and
      knowledge obtained by earlier experiments and simulations. Since such models tend
      to be large in size and complicated in structure, appropriate software frameworks
      for supporting modeling activities are required. A software platform,
      PhysioDesigner, has been developed, which supports the process of creating
      multilevel models. Models developed on PhysioDesigner are established in an XML
      format called PHML. Every physiological entity in a model is represented as a
      module, and hence a model constitutes an aggregation of modules. When the number
      of entities of which the model is comprised is large, it is difficult to manage
      the entities manually, and some semiautomatic assistive functions are necessary.
      In this article, which focuses particularly on recently developed features of the
      platform for building large-scale models utilizing a template/instance framework
      and morphological information, the PhysioDesigner platform is introduced. 

PMID- 24110990
TI  - Employing in-vivo molecular imaging in simulating and validating tumor growth.
AB  - During the last decades, especially via the EU initiative related to the Virtual
      Physiological Human, significant progress has been made in advancing "in-silico"
      computational models to produce accurate and reliable tumor growth simulations.
      However, currently most attempts to validate the outcome of the models are either
      done in-vitro or ex-vivo after tumor resection. In this work, we incorporate
      information provided by fluorescence molecular tomography performed in-vivo into
      a mathematical model that describes tumor growth. The outcome is validated
      against tumor evolution snapshots captured in-vivo using advanced molecular
      probes in laboratory animals. The simulations are inline with the actual in-vivo
      growth and although alternative modeling parameters can lead to similar results
      challenging for additional microscopic information and imaging modalities to
      drive the in-silico models, they all show that hypoxia plays a dominant role in
      the evolution of the tumor under study. 

PMID- 24110992
TI  - Standards and tools supporting collaborative development of the virtual
      physiological human.
AB  - The development of a virtual physiological human has an ambitious goal that
      requires the participation of a large and diverse community of scientists. To be
      successful in achieving this goal, members of this community must be able to
      share their work and easily collaborate on new developments and novel
      applications of existing work. To aid in this, various standardization projects
      have evolved as part of the Physiome community, as well as supporting
      computational tools and infrastructure. We present here an overview of the
      current state of these standardization efforts and key tools that support the
      collaborative development, integration, and exchange of computational physiology
      models under the Physiome umbrella. 

PMID- 24110991
TI  - Cellular automaton model for simulating tissue-specific intestinal
      electrophysiological activity.
AB  - Depletion of interstitial cell of Cajal (ICC) networks is known to occur in
      various gastrointestinal (GI) motility disorders. Although techniques for
      quantifying the structure of ICC networks are available, the ICC network
      structure-function relationships are yet to be well elucidated. Existing methods
      of relating ICC structure to function are computationally expensive, and it is
      difficult to up-scale them to larger multiscale simulations. A new cellular
      automaton model for simulating tissue-specific slow wave propagation was
      developed, and in preliminary studies the automaton model was applied on jejunal
      ICC network structures from wild-type and 5-HT2B receptor knockout (ICC depleted)
      mice. Two metrics were also developed to quantify the simulated propagation
      patterns: 1) ICC and 2) non-ICC activation lag metrics. These metrics measured
      the average delay in time taken for the slow wave to propagate across the ICC and
      non-ICC domain throughout the entire network compared to the theoretical fastest
      propagation, respectively. Slow wave propagation was successfully simulated
      across the ICC networks with greatly reduced computational time compared to
      previous methods, and the propagation pattern metrics quantitatively revealed an
      impaired propagation during ICC depletion. In conclusion, the developed slow wave
      propagation model and propagation pattern metrics offer a computationally
      efficient framework for relating ICC structure to function. These tools can now
      be further applied to define ICC structure-function relationships across various
      spatial and temporal scales. 

PMID- 24110993
TI  - In silico oncology: exploiting clinical studies to clinically adapt and validate
      multiscale oncosimulators.
AB  - This paper presents a brief outline of the notion and the system of oncosimulator
      in conjunction with a high level description of the basics of its core multiscale
      model simulating clinical tumor response to treatment. The exemplary case of lung
      cancer preoperatively treated with a combination of chemotherapeutic agents is
      considered. The core oncosimulator model is based on a primarily top-down,
      discrete entity - discrete event multiscale simulation approach. The critical
      process of clinical adaptation of the model by exploiting sets of multiscale data
      originating from clinical studies/trials is also outlined. Concrete clinical
      adaptation results are presented. The adaptation process also conveys important
      aspects of the planned clinical validation procedure since the same type of
      multiscale data - although not the same data itself- is to be used for clinical
      validation. By having exploited actual clinical data in conjunction with
      plausible literature-based values of certain model parameters, a realistic tumor
      dynamics behavior has been demonstrated. The latter supports the potential of the
      specific oncosimulator to serve as a personalized treatment optimizer following
      an eventually successful completion of the clinical adaptation and validation
      process. 

PMID- 24110994
TI  - Modeling spatial population dynamics of stem cell lineage in wound healing and
      cancerogenesis.
AB  - Modeling the dynamics of cell population in tissues involving stem cell niches
      allows insight into the control mechanisms of the important wound healing
      process. It is well known that growth and divisions of stem cells are mainly
      repressed by niche cells, but can also be activated by signals released from
      wound. In addition, the proliferation and differentiation among three different
      types of cell: stem cells (SCs), intermediate progenitor cells (IPCs), and fully
      differentiated cells (FDCs) in stem cell lineage are under different activation
      and inhibition controls. We have developed a novel stochastic spatial dynamic
      model of cells. We can characterize not only overall cell population dynamics,
      but also details of temporal-spatial relationship of individual cells within a
      tissue. In our model, the shape, growth, and division of each cell are modeled
      using a realistic geometric model. Furthermore, the inhibited growth rate,
      proliferation and differentiation probabilities of individual cells are modeled
      through feedback loops controlled by secreted factors and wound signals from
      neighboring cells. With specific proliferation and differentiation probabilities,
      the actual division type that each cell will take is chosen by a Monte Carlo
      sampling process. With simulations, we study the effects of different strengths
      of wound signals to wound healing behaviors. We also study the correlations
      between chronic wound and cancerogenesis. 

PMID- 24110996
TI  - Complexity of heart rate variability in type 2 diabetes - effect of
      hyperglycemia.
AB  - Heart rate variability (HRV) is reduced in diabetes mellitus (DM) patients,
      suggesting dysfunction of cardiac autonomic regulation which has been associated
      with increased risk for pathological cardiac events. In this paper, we examined
      changes in HRV complexity in association to blood glucose level (BGL) and
      duration of diabetes. Resting HRV and BGL measurements of 32 healthy controls and
      54 type 2 DM (T2DM) patients were analyzed. HRV complexity was assessed using
      Shannon entropy, sample entropy (SampEn), multiscale entropy (MSE), and
      multiscale Renyi entropy. HRV complexity increased with hyperglycemia indicated
      by increases in Shannon entropy and MSE and decreases in Renyi entropy for
      negative orders. Diabetes duration was strongly associated with Renyi entropy
      which increased for positive orders and decreased for negative orders as a
      function of disease duration. Shannon entropy, SampEn and MSE did not correlate
      with disease duration. 

PMID- 24110995
TI  - Refined multiscale entropy analysis of heart period and QT interval variabilities
      in long QT syndrome type-1 patients.
AB  - This study assesses complexity of cardiovascular control in patients affected by
      type-1 variant of long QT (LQT1) syndrome. Complexity was assessed by refined
      multiscale entropy of heart period (HP) and QT interval variabilities. HP was
      taken as the time distance between two consecutive R peaks (RR) and QT interval
      was approximated as the time distance between the R-peak and T-wave apex (RTa)
      and between R-peak and T-wave end (RTe). RR, RTa and RTe intervals were
      automatically extracted from 24h Holter recordings and the daytime period was
      analyzed (from 02:00 to 06:00 PM). Non mutation carrier (NMC) individuals (n=11),
      utilized as a control group, were taken from the same family line of the mutation
      carrier (MC) subjects (n=26). We found that, while NMC and MC groups were
      indistinguishable based on time domain and complexity analyses of RR dynamics,
      complexity analysis of RTa and RTe variabilities clearly separates the two
      populations and suggests an impairment in the cardiac control mechanisms acting
      on the ventricles.

PMID- 24110997
TI  - Using Renyi entropy to detect early cardiac autonomic neuropathy.
AB  - Cardiac Autonomic Neuropathy (CAN) is a disease that involves nerve damage
      leading to abnormal control of heart rate. CAN affects the correct operation of
      the heart and in turn leads to associated arrhythmias and heart attack. An open
      question is to what extent this condition is detectable by the measurement of
      Heart Rate Variability (HRV). An even more desirable option is to detect CAN in
      its early, preclinical stage, to improve treatment and outcomes. In previous work
      we have shown a difference in the Renyi spectrum between participants identified
      with well-defined CAN and controls. In this work we applied the multi-scale Renyi
      entropy for identification of early CAN in diabetes patients. Results suggest
      that Renyi entropy derived from a 20 minute, Lead-II ECG recording, forms a
      useful contribution to the detection of CAN even in the early stages of the
      disease. The positive alpha parameters (1 <= alpha <= 5) associated with the
      Renyi distribution indicated a significant difference (p < 0.00004) between
      controls and early CAN as well as definite CAN. This is a significant achievement
      given the simple nature of the information collected, and raises prospects of a
      simple screening test and improved outcomes of patients. 

PMID- 24110998
TI  - Beat to beat variability of embryonic chick heart cells under septic conditions:
      application and evaluation of entropy as well as fractal measures.
AB  - Extracardiac factors of heart rate variability have commonly been investigated
      using linear and nonlinear methods for a long time. Recently, intracardiac
      mechanisms on an electrophysiological basis have been found to be also important.
      This work is focused on the evaluation of complex measures of temporal signals
      gained with microelectrode measurements of embryonic chick heart aggregates.
      Septic conditions were mimicked in vitro by lipopolysaccharide (LPS)
      administration in order to investigate the influence on beat to beat variability.
      Surrogate data analysis revealed high statistical significances for normalized
      complexity measures. 

PMID- 24110999
TI  - Heart rate complexity and cardiac sympathetic dysinnervation in patients with
      type 2 diabetes mellitus.
AB  - Cardiovascular autonomic neuropathy (CAN) is one of the most severe complications
      of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate
      associations of cardiac sympathetic dysinnervation (CSD; by (123)I-MIBG
      scintigraphy) with short-term heart rate variability (HRV) measured by
      traditional vs. complexity markers. ECG was measured in 31 diabetic patients
      during rest over a period of 5 minutes and HRV quantified in different domains
      (time and frequency domain, scaling properties, symbolic dynamics). (123)I-MIBG
      scintigraphy identified 16 patients with CSD. Resting heart rate was increased
      and HRV reduced in these patients. In a subgroup of 16 patients ECG was also
      measured during standing. Changes in several HRV measures upon standing
      demonstrated cardiac responsiveness to orthostatic stress. Strong correlations
      between HRV, measured during standing, and CSD were observed with metrics based
      on symbolic dynamics. In conclusion, HRV assessment during standing may be useful
      for assessing cardiac sympathetic dysinnervation in patients with type 2 diabetes
      mellitus. 

PMID- 24111000
TI  - Influence of age and gender on complexity measures for short term heart rate
      variability analysis in healthy subjects.
AB  - Short-term heart rate variability (HRV) analyses (less than 30 min) are suitable
      for ambulatory care and patient monitoring and can provide an almost immediate
      test result. Short-term 5 min HRV indices from nonlinear dynamics were determined
      from 782 females and 1124 males from the KORA S4 database. We applied various
      fractal and complexity measures with focus on entropies and investigated the
      influence of age in terms of five age decades (25-34, 35-44, 45-54, 55-64 and 65
      74 years) and gender on these HRV indices. The analyses revealed significant
      modifications of the indices especially by age but partly also by gender
      especially in the younger groups. These results should be considered in future
      studies applying nonlinear dynamics, especially if major age and gender
      differences between the investigated groups are expected.

PMID- 24111001
TI  - Laguerre-Volterra identification of spike-timing-dependent plasticity from
      spiking activity: a simulation study.
AB  - This paper presents a Laguerre-Volterra methodology for identifying a plasticity
      learning rule from spiking neural data with four components: 1) By analyzing
      input-output spiking data, the effective contribution of an input on the output
      firing probability can be quantified with weighted Volterra kernels. 2) The
      weight of these Volterra kernels can be tracked over time using the stochastic
      state point processing filtering algorithm (SSPPF) 3) Plasticity system Volterra
      kernels can be estimated by treating the tracked change in weight over time as
      the plasticity system output and the spike timing data as the input. 4) Laguerre
      expansion of all Volterra kernels allows for minimization of open parameters
      during estimation steps. A single input spiking neuron with Spike-timing
      dependent plasticity (STDP) and prolonged STDP induction is simulated. Using the
      spiking data from this simulation, the amplitude of the STDP learning rule and
      the time course of the induction is accurately estimated. This framework can be
      applied to identify plasticity for more complicated plasticity paradigms and is
      applicable to in vivo data. 

PMID- 24111002
TI  - Synchrony of high frequency oscillations in the human epileptic brain.
AB  - We have applied wavelet phase coherence (WPC) to human iEEG data to characterize
      the spatial and temporal interactions of high frequency oscillations (HFOs; >80
      Hz). Quantitative analyses were performed on iEEG segments from four patients
      with extratemporal lobe epilepsy. Interelectrode synchrony was measured using WPC
      before, during and after seizure activity. The WPC profiles of HFOs were able to
      elucidate the seizure from non-seizure state in all four patients and for all
      seizures studied (n=10). HFO synchrony was consistently transient and of weak to
      moderate strength during non-seizure activity, while weak to very strong
      coherence, of prolonged duration, was observed during seizures. Several studies
      have suggested that HFOs may have a significant role in the process of
      epileptogenesis and seizure genesis. As epileptic seizures result from
      disturbances in the regular electrical activity present in given areas of the
      brain, studying the interactions between fast brain waves, recorded
      simultaneously and from many different brain regions, may provide more
      information of which brain areas are interacting during ictal and interictal
      activity. 

PMID- 24111003
TI  - Information-theoretic metric learning: 2-D linear projections of neural data for
      visualization.
AB  - Intracortical neural recordings are typically high-dimensional due to many
      electrodes, channels, or units and high sampling rates, making it very difficult
      to visually inspect differences among responses to various conditions. By
      representing the neural response in a low-dimensional space, a researcher can
      visually evaluate the amount of information the response carries about the
      conditions. We consider a linear projection to 2-D space that also parametrizes a
      metric between neural responses. The projection, and corresponding metric, should
      preserve class-relevant information pertaining to different behavior or stimuli.
      We find the projection as a solution to the information-theoretic optimization
      problem of maximizing the information between the projected data and the class
      labels. The method is applied to two datasets using different types of neural
      responses: motor cortex neuronal firing rates of a macaque during a center-out
      reaching task, and local field potentials in the somatosensory cortex of a rat
      during tactile stimulation of the forepaw. In both cases, projected data points
      preserve the natural topology of targets or peripheral touch sites. Using the
      learned metric on the neural responses increases the nearest-neighbor
      classification rate versus the original data; thus, the metric is tuned to
      distinguish among the conditions. 

PMID- 24111004
TI  - Decoding the evolving grasping gesture from electroencephalographic (EEG)
      activity.
AB  - Shared control is emerging as a likely strategy for controlling neuroprosthetic
      devices, in which users specify high level goals but the low-level implementation
      is carried out by the machine. In this context, predicting the discrete goal is
      necessary. Although grasping various objects is critical in determining
      independence in daily life of amputees, decoding of different grasp types from
      noninvasively recorded brain activity has not been investigated. Here we show
      results suggesting electroencephalography (EEG) is a feasible modality to extract
      information on grasp types from the user's brain activity. We found that the
      information about the intended grasp increases over the grasping movement, and is
      significantly greater than chance up to 200 ms before movement onset. 

PMID- 24111005
TI  - Frontal theta EEG dynamics in a real-world air traffic control task.
AB  - Mental workload and time-on-task effect are two major factors expediting fatigue
      progress, which leads to performance decline and/or failure in real-world tasks.
      In the present study, electroencephalography (EEG) is applied to study mental
      fatigue development during an air traffic control (ATC) task. Specifically, the
      frontal theta EEG dynamics are firstly dissolved into a unique frontal
      independent component (IC) through a novel time-frequency independent component
      analysis (tfICA) method. Then the temporal fluctuations of the identified frontal
      ICs every minute are compared to workload (reflected by number of clicks per
      minute) and time-on-task effect by correlational analysis and linear regression
      analysis. It is observed that the frontal theta activity significantly increase
      with workload augment and time-on-task. The present study demonstrates that the
      frontal theta EEG activity identified by tfICA method is a sensitive and reliable
      metric to assess mental workload and time-on-task effect in a real-world task,
      i.e., ATC task, at the resolution of minute(s). 

PMID- 24111006
TI  - Decoding of the sound frequency from the steady-state neural activities in rat
      auditory cortex.
AB  - In the auditory cortex, onset activities have been extensively investigated as a
      cortical representation of sound information such as sound frequency. Yet, less
      attention has been paid to date to steady-state activities following the onset
      activities. In this study, we used machine learning to investigate whether steady
      state activities in the presence of continuous sounds represent the sound
      frequency. Sparse Logistic Regression (SLR) decoded the sound frequency from band
      specific power or phase locking value (PLV) of local field potentials (LFP) from
      the fourth layer of the auditory cortex of anesthetized rats. Consequently, we
      found that SLR was able to decode the sound frequency from steady-state neural
      activities as well as onset activities. This result demonstrates that the steady
      state activities contain information about the sound such as sound frequency. 

PMID- 24111007
TI  - Reconstructing surface EMG from scalp EEG during myoelectric control of a closed
      looped prosthetic device.
AB  - In this study, seven able-bodied human subjects controlled a robotic gripper with
      surface electromyography (sEMG) activity from the biceps. While subjects
      controlled the gripper, they felt the forces measured by the robotic gripper
      through an exoskeleton fitted on their non-dominant left arm. Subjects were
      instructed to identify objects with the force feedback provided by the
      exoskeleton. While subjects operated the robotic gripper, scalp
      electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS)
      were recorded. We developed neural decoders that used scalp EEG to reconstruct
      the sEMG used to control the robotic gripper. The neural decoders used a genetic
      algorithm embedded in a linear model with memory to reconstruct the sEMG from a
      plurality of EEG channels. The performance of the decoders, measured with Pearson
      correlation coefficients (median r-value = 0.59, maximum r-value = 0.91) was
      found to be comparable to previous studies that reconstructed sEMG linear
      envelopes from neural activity recorded with invasive techniques. These results
      show the feasibility of developing EEG-based neural interfaces that in turn could
      be used to control a robotic device. 

PMID- 24111008
TI  - High accuracy decoding of user intentions using EEG to control a lower-body
      exoskeleton.
AB  - Brain-Machine Interface (BMI) systems allow users to control external mechanical
      systems using their thoughts. Commonly used in literature are invasive techniques
      to acquire brain signals and decode user's attempted motions to drive these
      systems (e.g. a robotic manipulator). In this work we use a lower-body
      exoskeleton and measure the users brain activity using non-invasive
      electroencephalography (EEG). The main focus of this study is to decode a
      paraplegic subject's motion intentions and provide him with the ability of
      walking with a lower-body exoskeleton accordingly. We present our novel method of
      decoding with high offline evaluation accuracies (around 98%), our closed loop
      implementation structure with considerably short on-site training time (around 38
      sec), and preliminary results from the real-time closed loop implementation
      (NeuroRex) with a paraplegic test subject. 

PMID- 24111009
TI  - Novel use of Empirical Mode Decomposition in single-trial classification of motor
      imagery for use in brain-computer interfaces.
AB  - This paper presents a novel method, based on multi-channel Empirical Mode
      Decomposition (EMD), of classifying the electroencephalogram (EEG) recordings of
      imagined movement by a subject within a brain-computer interfacing (BCI)
      framework. EMD is a technique that divides any non-linear or non-stationary
      signal into groups of frequency harmonics, called Intrinsic Mode Functions
      (IMFs). As frequency is a key component of both IMFs and the MU rhythm (8-13 Hz
      brain activity generated during motor imagery), IMFs are then grouped by
      frequency. EMD is applied to the recordings from two electrodes for each trial
      and the resulting IMFs are grouped according to peak-frequency band via
      Hierarchical Clustering Analysis (HCA). The cluster containing the frequency band
      of the MU rhythm (8-13 Hz) is then selected and the sum-total of the IMFs from
      each electrode are summed together. A simple linear classifier is then sufficient
      to classify the motor-imagery with 89% sensitivity from a separate test set.

PMID- 24111010
TI  - Subject-to-subject transfer for CSP based BCIs: feature space transformation and
      decision-level fusion.
AB  - Modern Brain Computer Interfaces (BCIs) usually require a calibration session to
      train a machine learning system before each usage. In general, such trained
      systems are highly specialized to the subject's characteristic activation
      patterns and cannot be used for other sessions or subjects. This paper presents a
      feature space transformation that transforms features generated using subject
      specific spatial filters into a subject-independent feature space. The
      transformation can be estimated from little adaptation data of the subject.
      Furthermore, we combine three different Common Spatial Pattern based feature
      extraction approaches using decision-level fusion, which enables BCI use when
      little calibration data is available, but also outperformed the subject-dependent
      reference approaches for larger amounts of training data. 

PMID- 24111011
TI  - Sensitivity and specificity of upper extremity movements decoded from
      electrocorticogram.
AB  - Electrocorticogram (ECoG)-based brain computer interfaces (BCI) can potentially
      be used for control of arm prostheses. Restoring independent function to BCI
      users with such a system will likely require control of many degrees-of-freedom
      (DOF). However, our ability to decode many-DOF arm movements from ECoG signals
      has not been thoroughly tested. To this end, we conducted a comprehensive study
      of the ECoG signals underlying 6 elementary upper extremity movements. Two
      subjects undergoing ECoG electrode grid implantation for epilepsy surgery
      evaluation participated in the study. For each task, their data were analyzed to
      design a decoding model to classify ECoG as idling or movement. The decoding
      models were found to be highly sensitive in detecting movement, but not specific
      in distinguishing between different movement types. Since sensitivity and
      specificity must be traded-off, these results imply that conventional ECoG grids
      may not provide sufficient resolution for decoding many-DOF upper extremity
      movements. 

PMID- 24111012
TI  - Sub-mm functional decoupling of electrocortical signals through closed-loop BMI
      learning.
AB  - Volitional control of neural activity lies at the heart of the Brain-Machine
      Interface (BMI) paradigm. In this work we investigated if subdural field
      potentials recorded by electrodes < 1mm apart can be decoupled through closed
      loop BMI learning. To this end, we fabricated custom, flexible microelectrode
      arrays with 200 um electrode pitch and increased the effective electrode area by
      electrodeposition of platinum black to reduce thermal noise. We have chronically
      implanted these arrays subdurally over primary motor cortex (M1) of 5 male Long
      Evans Rats and monitored the electrochemical electrode impedance in vivo to
      assess the stability of these neural interfaces. We successfully trained the
      rodents to perform a one-dimensional center-out task using closed-loop brain
      control to adjust the pitch of an auditory cursor by differentially modulating
      high gamma (70-110 Hz) power on pairs of surface microelectrodes that were
      separated by less than 1 mm.

PMID- 24111013
TI  - Selection and control of limb posture for stability.
AB  - Impedance control can be used to stabilize the limb against both instability and
      unpredictable perturbations. Limb posture influences motor noise, energy usage
      and limb impedance as well as their interaction. Here we examine whether subjects
      use limb posture as part of a mechanism to regulate limb stability. Subjects
      performed stabilization tasks while attached to a two dimensional robotic
      manipulandum which generated a virtual environment. Subjects were instructed that
      they could perform the stabilization task anywhere in the workspace, while the
      chosen postures were tracked as subjects repeated the task. In order to
      investigate the mechanisms behind the chosen limb postures, simulations of the
      neuro-mechanical system were performed. The results indicate that posture
      selection is performed to provide energy efficiency in the presence of force
      variability. 

PMID- 24111014
TI  - Hybrid nonlinear model of the angular vestibulo-ocular reflex.
AB  - A hybrid nonlinear bilateral model for the horizontal angular vestibulo-ocular
      reflex (AVOR) is presented in this paper. The model relies on known
      interconnections between saccadic burst circuits in the brainstem and ocular
      premotor areas in the vestibular nuclei during slow and fast phase intervals. A
      viable switching strategy for the timing of nystagmus events is proposed.
      Simulations show that this hybrid model replicates AVOR nystagmus patterns that
      are observed in experimentally recorded data. 

PMID- 24111015
TI  - Human body contour data based activity recognition.
AB  - This research work is aimed to develop autonomous bio-monitoring mobile robots,
      which are capable of tracking and measuring patients' motions, recognizing the
      patients' behavior based on observation data, and providing calling for medical
      personnel in emergency situations in home environment. The robots to be developed
      will bring about cost-effective, safe and easier at-home rehabilitation to most
      motor-function impaired patients (MIPs). In our previous research, a full
      framework was established towards this research goal. In this research, we aimed
      at improving the human activity recognition by using contour data of the tracked
      human subject extracted from the depth images as the signal source, instead of
      the lower limb joint angle data used in the previous research, which are more
      likely to be affected by the motion of the robot and human subjects. Several
      geometric parameters, such as, the ratio of height to weight of the tracked human
      subject, and distance (pixels) between centroid points of upper and lower parts
      of human body, were calculated from the contour data, and used as the features
      for the activity recognition. A Hidden Markov Model (HMM) is employed to classify
      different human activities from the features. Experimental results showed that
      the human activity recognition could be achieved with a high correct rate. 

PMID- 24111016
TI  - Spectral modulation of frontal EEG activities during motor skill acquisition:
      task familiarity monitoring using single-channel EEG.
AB  - This study investigates the modulation of frontal EEG dynamics with respect to
      progress in motor learning. Using a computerized visual-motor task similar to
      mirror drawing, our work demonstrated that overall EEG activities in all
      frequency bands decreased with an increase in motor task familiarity. In
      particular, frontal EEG activities in delta band of the whole trial and gamma
      band at the beginning of each trial are having a significant negative
      relationship with the overall familiarity level of the task. The findings suggest
      that frontal EEG spectra are significantly modulated during motor skill
      acquisition. 

PMID- 24111017
TI  - Fuzzy logic control of ankle movement using multi-electrode intraspinal
      microstimulation.
AB  - In this paper, we propose a fuzzy logic control (FLC) for control of ankle
      movement using multi-electrode intraspinal microstimulation (ISMS). It has been
      demonstrated that ISMS via multi-electrode implanted into a given motor pool has
      several advantages over the single-electrode ISMS. In the current study, we
      investigate the closed-loop control of ankle movement using multi-electrode ISMS.
      For this purpose, a pair of electrodes was implanted into the each motor pool of
      dorsiflexor and plantar flexor muscles in the spinal cord. For each muscle, an
      independent FLC was designed. The response of neuromuscular system has a time
      delay with respect to the input stimulation. To compensate the effect of time
      delay, the future value of desired response was considered as the input of the
      FLC as well as the error signal. The results of experiments on animals show that
      the proposed control framework can provide a good tracking performance. 

PMID- 24111018
TI  - Feedback compensation of intrinsic muscle properties during torque regulation
      tasks.
AB  - Many functional tasks require regulating appropriate forces or torques even under
      unpredictable disturbances. However, how this regulation can be achieved remains
      poorly understood. Limb impedance describes the relationship between externally
      imposed displacements to the limb and the changes in force or torque generated in
      response. Low limb impedance is preferred during torque regulation tasks.
      However, low-frequency impedance increases with muscle activation, which is
      counterproductive to torque regulation. The purpose of this study was to quantify
      the ability to voluntarily reduce limb impedance during torque regulation tasks,
      and to assess if the observed performance is near optimal given the challenges
      posed by activation-dependent muscle properties and time delays in the
      neuromuscular system. By examining elbow impedance measured in experiments and
      predicted by a biomechanical model with an optimal controller, our results
      demonstrated that individuals can reduce the low-frequency components (below 1
      Hz) of elbow impedance during forceful contractions, and that this performance is
      similar to those predicted by an optimal feedback controller. These findings
      suggest that neural feedback can compensate for intrinsic muscle properties in a
      near-optimal manner, thereby allowing torque to be regulated at frequencies below
      ~ 1 Hz.

PMID- 24111019
TI  - An e-nose concept based on semiconductor-assisted field ionization and gaseous
      discharge on arrays of whiskered nanowires.
AB  - Electronic nose systems employ an array of gas detectors each tailored to respond
      differently to a range of odors. In the presence of a particular gaseous
      compound, the responses of sensors form a signature that is analyzed in the
      signal transduction process. The gas sensing cells operate by a variety of
      different mechanisms, but generally, catalyst based sensors suffer from issues
      such as poor specificity, slow response time, and irreversibility. This work
      introduces a novel approach towards instantaneous and selective discrimination of
      gases based on their unique ionization properties: electric breakdown voltage and
      field ionization current-voltage characteristic. Synthesized gold and silicon
      nanowires, covered with sharp nanoscale whiskers, exhibited anomalously strong
      discharge and field ionization characteristics at very low bias voltages. The
      anomalous field ionization phenomenon was attributed to the combination of
      geometric field enhancement and the presence of localized surface states at the
      surface of the emitters. 

PMID- 24111020
TI  - All-carbon graphene bioelectronics.
AB  - We report nano field-effect transistor (nanoFET) biosensors built from the
      monolithic integration of graphene and graphite. The monolithic integration
      enables nanoscopic field-effect detection of chemical and biological signals with
      mechanically flexible and robust interface with biological systems in several
      respects. Our nanoFET biosensors exhibit superior detection sensitivity,
      mechanical flexibility and nanoscopic detection resolution. First, we demonstrate
      that electrical detection can be achieved from nanoscale electric field
      modulation of the graphene channel while the signal integrity is not perturbed by
      mechanical deflection of graphene nanoFET sensors. Such capability is introduced
      by the advanced design of monolithic graphene-graphite without any need for metal
      graphene heterointerfaces. Second, we explore the chemical detection capability
      of graphene nanoFET sensors, and show that our sensors are responsive to
      localized chemical environmental changes/perturbations. Our nanoFET sensors not
      only show clear response to nanoscopic charge perturbation but also demonstrate
      potential 3-D sensing capability due to the advanced monolithic graphene-graphite
      mechanical design. These unique capabilities of our monolithic graphene-graphite
      bioelectronics could be exploited in chemical and biological detection and
      conformal interface with biological systems in the future. 

PMID- 24111021
TI  - Toward implantable glucometer: design, modeling and experimental results.
AB  - We put forward an implantable glucometers using a biologically inspired sensor
      (BioS) method. In this method, engineered glucokinase (GLK) molecules are used as
      nanoscale glucometers. Herein, we describe two computational and experimental
      models of GLKs exposed to glucose molecules. The simulation results significantly
      show the detection of GLK binding to glucose. We thereafter reveal the
      applicability of this technique for continuous glucose monitoring by
      demonstrating and discussing the experimental results. Based on these results the
      glucose measurement with various glucose concentrations (0.5 mM, 1 mM and 2.5 mM)
      were precisely performed and repeated for more than 4 weeks. These results prove
      the advantage of proposed BioS method for continuous measurement of glucose. 

PMID- 24111022
TI  - A wireless and batteryless neural headstage with optical stimulation and
      electrophysiological recording.
AB  - This paper presents a miniature Optogenetics headstage for wirelessly stimulating
      the brain of rodents with an implanted LED while recording electrophysiological
      data from a two-channel custom readout. The headstage is powered wirelessly using
      an inductive link, and is built using inexpensive commercial off-the-shelf
      electronic components, including a RF microcontroller and a printed antenna. This
      device has the capability to drive one light-stimulating LED and, at the same
      time, capture and send back neural signals recorded from two microelectrode
      readout channels. Light stimulation uses flexible patterns that allow for easy
      tuning of light intensity and stimulation periods. For driving the LED, a low
      pass filtered digitally-generated PWM signal is employed for providing a flexible
      pulse generation method that alleviates the need for D/A converters. The proposed
      device can be powered wirelessly into an animal chamber using inductive energy
      transfer, which enables compact, light-weight and cost-effective smart animal
      research systems. The device dimensions are 15*25*17 mm; it weighs 7.4 grams and
      has a data transmission range of more than 2 meters. Different types of LEDs with
      different power consumptions can be used for this system. The power consumption
      of the system without the LED is 94.52 mW. 

PMID- 24111023
TI  - Biomimetic electrical stimulation platform for neural differentiation of retinal
      progenitor cells.
AB  - Electrical activity is abundant in early retinal development, and electrical
      stimulation has been shown to modulate embryonic stem cell differentiation
      towards a neuronal fate. The goal of this study was to simulate in vitro retinal
      developmental electrical activity to drive changes in mouse retinal progenitor
      cell (mRPC) gene expression and morphology. We designed a biomimetic electrical
      stimulation protocol based on spontaneous waves present during retinal
      development, and applied it to retinal progenitor cells (RPCs) over 3 days of
      culture. Analysis of protein localization and calcium dynamics, indicate that
      mRPCs undergo functional neuronal maturation. Our findings suggest that this type
      of electrical stimulation may be utilized for application in neural tissue
      engineering and open possibilities for understanding mechanisms guiding active
      electric membrane development and functional organization during early
      retinogenesis. 

PMID- 24111024
TI  - Performance of a 6-degree-of-freedom active microsurgical manipulator in handheld
      tasks.
AB  - This paper presents the first experimental results from human users of a new 6
      degree-of-freedom handheld micromanipulator. This is the latest prototype of a
      fully-handheld system, known as "Micron," which performs active compensation of
      hand tremor for microsurgery. The manipulator is a miniature Gough-Stewart
      platform incorporating linear ultrasonic motors that provide a cylindrical
      workspace 4 mm long and 4 mm wide. In addition, the platform allows the
      possibility of imposing a remote center of motion for controlling motion not only
      at the tip but also at the entry point in the sclera of the eye. We demonstrate
      hand tremor reduction in both static and dynamic micromanipulation tasks on a
      rubber pad. The handheld performance is also evaluated in an artificial eye model
      while imposing a remote center of motion. In all cases, hand tremor is
      significantly reduced. 

PMID- 24111025
TI  - Improvement of optical coherence tomography using active handheld
      micromanipulator in vitreoretinal surgery.
AB  - An active handheld micromanipulator has been developed to cancel hand tremor
      during microsurgery. The micromanipulator is also applicable in optical coherence
      tomography to improve the quality of scanning and minimize surgical risks during
      the scans. The manipulator can maneuver the tool tip with six degrees of freedom
      within a cylindrical workspace 4 mm in diameter and 4 mm high. The imaging system
      is equipped with a 25-gauge Fourier-domain common-path OCT probe. This paper
      introduces the handheld OCT imaging system and techniques involved and presents
      stabilized OCT images of A-mode and M-mode scans in air and live rabbit eyes. We
      show the first demonstration of OCT imaging using the active handheld
      micromanipulator in vivo. 

PMID- 24111026
TI  - Evaluation of the potential of multi-modal sensors for respiratory motion
      prediction and correlation.
AB  - In modern robotic radiotherapy, precise radiation of moving tumors is possible by
      tracking external optical surrogates. The surrogates are used to compensate for
      time delays and to predict internal landmarks using a correlation model. The
      correlation depends significantly on the surrogate position and breathing
      characteristics of the patient. In this context, we aim to increase the accuracy
      and robustness of prediction and correlation models by using a multi-modal sensor
      setup. Here, we evaluate the correlation coefficient of a strain belt, an
      acceleration and temperature sensor (air flow) with respect to external optical
      sensors and one internal landmark in the liver, measured by 3D ultrasound. The
      focus of this study is the influence of breathing artefacts, like coughing and
      harrumphing. Evaluating seven subjects, we found a strong decrease of the
      correlation for all modalities in case of artefacts. The results indicate that no
      precise motion compensation during these times is possible. Overall, we found
      that apart from the optical markers, the strain belt and temperature sensor data
      show the best correlation to external and internal motion. 

PMID- 24111027
TI  - The introduction of a new robot for assistance in ophthalmic surgery.
AB  - This paper introduces the design and development of a new robotic system to
      assist surgeons performing ophthalmic surgeries. The robot itself is very compact
      and similar to an average human hand in size. Its primary application is
      intraocular micromanipulation in order to overcome the existing challenges in
      treatment of diseases like Retinal Vein Occlusion (RVO). The novel hybrid
      mechanism designed for this robot allows microscale motions and is stable in the
      presence of vibrations common in operation room (OR). The robotic system can be
      easily integrated into standard operation rooms and does not require modification
      of conventional surgical tools. This compact microsurgical system is suitable for
      mounting on the patient's head and thereby, solves the problem of patient motion.
      The compatibility of the robotic system with a real world surgical setup was
      evaluated and confirmed in this work. 

PMID- 24111029
TI  - A surgical robot with a heart-surface-motion synchronization mechanism for
      myoblast cell sheet transplantation.
AB  - Myoblast cell sheets are employed in the clinical treatment of heart disorders.
      We propose a surgical robot system with two endoscopic cameras, characterized by
      a double remote center of motion (RCM) mechanism, to realize heart-surface-motion
      synchronization movement for myoblast cell sheet transplantation on a beating
      heart surface. A robot system with the double RCM mechanism was developed for
      which the linear and rotation motions are totally isolated, and an experiment was
      conducted to evaluate the tracking accuracy of the robot system when tracking a
      randomly moving target. The tracking data were updated with a Polaris system at
      30 Hz. The experiment results showed linear and rotation tracking errors of 4.93
      +/- 5.92 mm and 2.54 +/- 5.44 degrees , respectively.

PMID- 24111028
TI  - Design of 3-DOF force sensing micro-forceps for robot assisted vitreoretinal
      surgery.
AB  - Vitreoretinal surgery is associated with serious complications that can easily
      stem from excessive tissue manipulation forces while the forces required for such
      surgery are routinely well below human tactile sensation. Despite the critical
      need in this area, there is still no practical vitreoretinal instrument that can
      sense both the axial and transverse tool-to-tissue interaction forces with sub-mN
      accuracy. In this study, we present the conceptual design and optimization of a 3
      degrees-of-freedom (DOF) force sensing micro-forceps as the next generation of
      our force sensing instruments. 4 fiber Bragg grating (FBG) strain sensors are
      integrated in the design to measure tool tip forces. 

PMID- 24111030
TI  - Proposal on 3-D endoscope by using grid-based active stereo.
AB  - In this paper, we propose a novel 3-D endoscope system by using grid-based active
      stereo. In the proposed system, projection of a waved-grid pattern that consists
      of vertical and horizontal sinusoidal lines realizes accurate shape acquisition
      in sub-pixel accuracy. We develop a small pattern projector implementable to a
      head of a ready-made endoscope, and examine 3-D shape reconstruction by actual
      equipment. As the result of the measurement for a known-shaped object, which is a
      hexagonal cylinder, the error of length measurement is below 0.9% and the error
      of angle measurement is below 2.2%. We make a measurement of animal organ meat,
      and confirm that the system can reconstruct a 3-D shape of the organ surface.

PMID- 24111031
TI  - Navigation technique for MR-endoscope system using a wireless accelerometer-based
      remote control device.
AB  - The MR-endoscope system can perform magnetic resonance (MR) imaging during
      endoscopy and show the images obtained by using endoscope and MR. The MR
      endoscope system can acquire a high-spatial resolution MR image with an
      intraluminal radiofrequency (RF) coil, and the navigation system shows the
      scope's location and orientation inside the human body and indicates MR images
      with a scope view. In order to conveniently perform an endoscopy and MR
      procedure, the design of the user interface is very important because it provides
      useful information. In this study, we propose a navigation system using a
      wireless accelerometer-based controller with Bluetooth technology and a
      navigation technique to set the intraluminal RF coil using the navigation system.
      The feasibility of using this wireless controller in the MR shield room was
      validated via phantom examinations of the influence on MR procedures and
      navigation accuracy. In vitro examinations using an isolated porcine stomach
      demonstrated the effectiveness of the navigation technique using a wireless
      remote-control device. 

PMID- 24111032
TI  - Enhanced vision system for laparoscopic surgery.
AB  - Laparoscopic surgery offers benefits to the patients but poses new challenges to
      the surgeons, including a limited field of view. In this paper, we present an
      innovative vision system that can be combined with a traditional laparoscope, and
      provides the surgeon with a global view of the abdominal cavity, bringing him or
      her closer to open surgery conditions. We present our first experiments performed
      on a testbench mimicking a laparoscopic setup: they demonstrate an important time
      gain in performing a complex task consisting bringing a thread into the field of
      view of the laparoscope. 

PMID- 24111033
TI  - High-resolution MR imaging of gastrointestinal tissue by intracavitary RF coil
      with remote tuning and matching technique for integrated MR-endoscope system.
AB  - The goal of this study is to establish novel medical technologies by combining
      magnetic resonance imaging (MRI) with endoscopy to improve diagnostic precision
      and the safety of endoscopic surgeries. One of the key components of the
      integrated magnetic resonance (MR) endoscope system is a radio-frequency (RF)
      coil; this detects the MR signal from tissue and should be placed inside the
      body. Resonance characteristics such as the resonant frequency and the impedance
      of the RF coil, which affect the quality of MR images, change depending on the
      electric properties of the surrounding tissue and the coil deformation.
      Therefore, the technique of remote tuning and matching of the RF coil was
      developed, and its feasibility was investigated using a developed intracavitary
      RF coil, 1.5 tesla MR scanner, and models of phantom and resected porcine
      stomach. As a result, the frequency tuning and impedance matching was remotely
      adjusted in both models. In addition, the signal-to-noise ratio (SNR) of MR
      images was improved up to 134%. The developed remote tuning and matching
      technique was able to adjust the resonant characteristics of RF coil and can
      contribute the improvement of MR image quality, which would facilitate safe and
      precise endoscopy and endoscopic surgeries. 

PMID- 24111034
TI  - Towards real-time in situ polyp detection in WCE images using a boosting-based
      approach.
AB  - This paper presents a new embeddable method for polyp detections in Wireless
      Capsule Endoscopic - WCE images. this approach consists first of extracting
      candidate polyps within the image using geometric considerations about related
      shape, and second, in classifying (polyp/non-polyp) obtained candidates by a
      boosting-based method using texture features. The proposed approach has been
      designed in accordance with the hardware constraints related to FPGA
      implementation for integration within WCE imaging device. The classification
      performance of the method have been evaluated on a large dataset of 300 polyps,
      and 1200 non-polyps images. Experiments show interesting and promising
      performance: the boosting-based classification is characterized by a sensitivity
      of 91%, a specificity of 95% and a false detection rate of 4.8%, the detection
      rate of the overall processing chain being of 68%. The performance of the
      boosting-based classification are in accordance with the most recent reference on
      this particular topic using the same dataset. Building of a dedicated WCE image
      database should permit the improvement of the global detection rate. 

PMID- 24111035
TI  - A knee arthroscopy simulator: design and validation.
AB  - Many challenges exist when teaching and learning arthroscopic surgery, carrying a
      high risk of damaging the joint during the learning process. To minimize risk,
      the use of arthroscopy simulators allows trainees to learn basic skills in a risk
      free environment before entering the operating room. A high-fidelity physical
      knee arthroscopy simulator is proposed to bridge the gap between surgeons and
      residents. The simulator is composed of modular and replaceable elements and can
      measure applied forces, instrument position and hand motion, in order to assess
      performance in real time. A construct validity study was conducted in order to
      assess the performance improvement of novices after practicing with the
      simulator. In addition, a face validity study involving expert surgeons indicated
      that the simulator provides a realistic scenario suitable for teaching basic
      skills. Future work involves the development of better metrics to assess user
      performance. 

PMID- 24111036
TI  - Development of perioperative glycemic control using an artificial endocrine
      pancreas.
AB  - It is well known that tight glycemic control (TGC) in patients with diabetes
      mellitus is the most important to reduce complications, such as nephropathy,
      neuropathy, and retinopathy. Also, surgical stress induced hyperglycemia leading
      to glucose toxicity is the main cause of infectious complications after surgery.
      Recently perioperative TGC has been proven an effective method to reduce
      postoperative infectious complications and accelerate enhanced recovery after
      surgery (ERAS), with the main purpose of short staying hospital. However,
      conventional TGC with open-loop glycemic control system is likely to induce not
      only occurrence of hypoglycemia but also unstable glycemic control. To solve
      these problems, we have involved introduction of novel glycemic control using an
      artificial pancreas (AP) with closed-loop glycemic control system since 2006. To
      date, this novel perioperative glycemic control was performed in more than 400
      surgical patients. As a result, we established stable and safe TGC using an AP to
      improve surgical outcomes without hypoglycemia. In this paper, we report current
      scientific evidence focusing on perioperative glycemic control using an AP. 

PMID- 24111037
TI  - A new control method depending on primary phase angle of transcutaneous energy
      transmission system for artificial heart.
AB  - A new control method for stabilizing output voltage of the transcutaneous energy
      transmission system for artificial heart is proposed. This method is primary
      side, is outside of the body, which is not depending on a signal transmission
      system from the implanted device. The impedance observed from primary side
      changes from inductive to capacitive and the output voltage decreases drastically
      when the output current is large and the coupling factor is higher than that of
      the optimal condition. In this case, the driving frequency should be changed to
      higher so that the phase angle of the primary impedance is zero degree. The
      preliminary examination showed that this control method can enhance the output
      voltage limit to twice and the feasibility of the primary side control. 

PMID- 24111038
TI  - Navigation for cochlear implantation.
AB  - A cochlear implant is an artificial sensory organ for patients with severe to
      profound hearing loss who have little benefit from hearing aids. The fact that
      more patients with previous temporal bone surgery or cranial malformations are
      receiving cochlear implants implies that the number of atypical cochlear
      implantation will continue to grow. Surgical navigation, or image-guided surgery
      may be helpful for surgeons who perform atypical surgeries. We report our
      research on an image-guided system specifically designed for otologic surgery
      with an improved surgeon-computer interface. 

PMID- 24111039
TI  - Emergency Life Support System aiming preprimed oxygenator.
AB  - Development have been achieved of a new blood pump for next generation
      Percutaneous Cardio-Pulmonary Support (PCPS) system and a novel surface coating
      method for silicone membrane hollow fiber by physical adsorption using a
      copolymer composed of a 2-Methacryloyloxyethyl phosphorylcholine (MPC) unit and a
      hydrophobic unit. The new blood pump, named the Troidal Convolution Pump (TCP),
      is based on the principle of a cascade pump and perfused 5 L/min and 350 mmHg at
      2450 rpm. The novel copolymer composed of 30% MPC unit and 3-(methacryloyloxy)
      propyltris (trimethylsiloxy) silane (MPTSSi) unit (PMMSi30) was the most suitable
      molecular design on a silicone surface. The PMMSi30 coated surface adsorbed 7.2 %
      as much protein a non-coated surface adsorbed.

PMID- 24111040
TI  - Interbeat control of a ventricular assist device for variable pump performance.
AB  - Pump performance is very important property in rotary blood pumps. Suitable pump
      performance often creates suitable blood flow regulation in long-term circulatory
      support. However, it is difficult to develop the blood pump with specific pump
      performance. In addition, optimal pump performance is still unknown. In this
      study, we have proposed a control method to implement variable pump performance
      in a single pump and evaluated the validity of the control method using computer
      simulation. The controller controls the dynamic change in the relationship
      between pump pressure head and flow rate by interbeat control. A repetitive
      control method was adopted in order to reduce cyclic error derived from the
      heartbeat. Simulation results indicate the possibility that the proposed
      controller can regulate so that the dynamic relationship between pressure head
      and pump flow is that of various type centrifugal pump. 

PMID- 24111041
TI  - Expansion capsules for diet control with artificial organ technology.
AB  - When we consider the medical economy, the Obesity is one of the leading
      preventable causes of death worldwide. However, a lot of previous scientific
      papers reported that 95% of obesity patients would not be able to control their
      weight by the diet. The surgical operation has been considered to the subjects
      with severe obesity. But, there is a possibility of complication or comorbidity
      in surgical operation. Tohoku University started to develop the expanding capsule
      with transcutaneous energy transmission system (TETS) having the same effect as
      the surgical operation. The capsule in the stomach will expand mechanically by
      energy transmission from outsides of the body, when the obesity patients will
      felt hungry. Small linear drive with folding umbrella type actuator would enable
      us the expansion of the diet capsules. Satisfactory characteristic of the energy
      transmission was obtained by the trial model of TETS during animal experiments.
      Animal experiments with healthy adult goats enabled us the evaluation of the
      inner stomach pressure time series changes, and feasibility study. Double blind
      test of the expanding capsule is now under planning. If the expanding capsule
      diet control system will be embodied, it becomes the gospel of the obese subject.

PMID- 24111042
TI  - The solution for the independence of bioelectric and biomagnetic signals is
      confirmed.
AB  - The theoretical solution for the independence of bioelectric and biomagnetic
      signals rising from volume sources was published by Jaakko Malmivuo in 1995 [1].
      In 2000 his research group published a clinical study on electro- and
      magnetocardiography which confirmed this result [2, 3]. In 2005 Iwasaki and co
      workers published a clinical study on the detection of epileptic foci with
      electro- and magnetoencephalo-graphy [4]. They came to similar result as Malmivuo
      et al. in their study on ECG and MCG. Because the theoretical solution is now
      confirmed independently by two research groups with two different clinical
      studies and different volume sources, there is no doubt that the problem of the
      independence of bioelectric and biomagnetic signals from volume sources is now
      solved. 

PMID- 24111043
TI  - A new feature extraction method based on autoregressive power spectrum for
      improving sEMG classification.
AB  - The feature extraction is an important step to achieve multifunctional prosthetic
      control based on surface electromyography (sEMG) pattern recognition. In this
      study, we propose a new sEMG feature extraction method which is based on
      autoregressive power spectrum (ARPS). An experiment with a task containing
      thirteen motion classes was developed to examine the effectiveness of this
      method. The results show that the new feature, ARPS, has better performance
      comparing with other two frequently used features, the time domain set (TDS) and
      autoregressive coefficients (ARC). The ARPS obtains the highest separability
      index (SI)-a metric measuring the discriminative ability of the sEMG feature. And
      the average classification errors of ARPS, TDS and ARC are 5.00%, 8.43% and 6.39%
      respectively. This suggests that the ARPS is suitable for the sEMG pattern
      recognition.

PMID- 24111044
TI  - Artifact removal algorithm for an EMG-based Silent Speech Interface.
AB  - An electromygraphic (EMG) Silent Speech Interface is a system which recognizes
      speech by capturing the electric potentials of the human articulatory muscles,
      thus enabling the user to communicate silently. This study deals with improving
      the EMG signal quality by removing artifacts: The EMG signals are captured by
      electrode arrays with multiple measuring points. On the resulting high
      dimensional signal, Independent Component Analysis is performed, and artifact
      components are automatically detected and removed. This method reduces the Word
      Error Rate of the silent speech recognizer by 9.9% relative on a development
      corpus, and by 13.9% relative on an evaluation corpus. 

PMID- 24111045
TI  - Improving EMG based classification of basic hand movements using EMD.
AB  - This paper presents a pattern recognition approach for the identification of
      basic hand movements using surface electromyographic (EMG) data. The EMG signal
      is decomposed using Empirical Mode Decomposition (EMD) into Intrinsic Mode
      Functions (IMFs) and subsequently a feature extraction stage takes place. Various
      combinations of feature subsets are tested using a simple linear classifier for
      the detection task. Our results suggest that the use of EMD can increase the
      discrimination ability of the conventional feature sets extracted from the raw
      EMG signal.

PMID- 24111046
TI  - A preliminary investigation of the effect of force variation for myoelectric
      control of hand prosthesis.
AB  - The myoelectric control of prostheses has been an important area of research for
      the past 40 years. Significant advances have been achieved with Pattern
      Recognition (PR) systems regarding the number of movements to be classified with
      high accuracy. However, practical robustness still needs further research. This
      paper focuses on investigating the effect of the change in force levels by
      transradial amputee persons on the performance of PR systems. Two below-elbow
      amputee persons participated in the study. Three levels of forces (low, medium,
      and high) were recorded for different hand grips with the help of visual feedback
      from the Electromyography (EMG) signals. Results showed that changing the force
      level degraded the performance of the myoelectric control system by up to 60%
      with 12 EMG channels for 4 hand grips and a rest position. We investigated
      different EMG feature sets in combination with a Linear Discriminant Analysis
      (LDA) classifier. The performance was slightly better with Time Domain (TD)
      features compared to Auto Regression (AR) coefficients and Root Mean Square (RMS)
      features. Finally, the error of the classification was considerably reduced to
      approximately 17% when the PR system was trained with all force levels. 

PMID- 24111047
TI  - Enhancing classification accuracy of wrist movement by denoising sEMG signals.
AB  - This paper presents identification of 4 different wrist movements by analyzing
      fore-arm surface Electromyogram (sEMG) signals. In order to reduce noise picked
      up during the recording, wavelet based denoising is applied using Daubechies
      mother wavelet. Spectral features along with Wilson's amplitude were extracted
      and given to a linear classifier. The experimental result shows better
      recognition performance using the given features when denoising is applied. The
      maximum accuracy for identification of four wrist movement was 97.5% which is
      quite significant as compared to the previous researches. 

PMID- 24111048
TI  - EMG signal morphology in essential tremor and Parkinson's disease.
AB  - The aim of this work was to differentiate patients with essential tremor from
      patients with Parkinson's disease. The electromyographic signal from the biceps
      brachii muscle was measured during isometric tension from 17 patients with
      essential tremor, 35 patients with Parkinson's disease, and 40 healthy controls.
      The EMG signals were high pass filtered and divided to smaller segments from
      which histograms were calculated using 200 histogram bins. EMG signal histogram
      shape was analysed with a feature dimension reduction method, the principal
      component analysis, and the shape parameters were used to differentiate between
      different patient groups. The height of the histogram and the side difference
      between left and right hand were the best discriminators between essential tremor
      and Parkinson's disease groups. With this method, it was possible to discriminate
      13/17 patients with essential tremor from 26/35 patients with Parkinson's disease
      and 14/17 patients with essential tremor from 29/40 healthy controls. 

PMID- 24111049
TI  - Design and implementation of a low power mobile CPU based embedded system for
      artificial leg control.
AB  - This paper presents the design and implementation of a new neural-machine
      interface (NMI) for control of artificial legs. The requirements of high
      accuracy, real-time processing, low power consumption, and mobility of the NMI
      place great challenges on the computation engine of the system. By utilizing the
      architectural features of a mobile embedded CPU, we are able to implement our
      decision-making algorithm, based on neuromuscular phase-dependant support vector
      machines (SVM), with exceptional accuracy and processing speed. To demonstrate
      the superiority of our NMI, real-time experiments were performed on an able
      bodied subject with a 20 ms window increment. The 20 ms testing yielded
      accuracies of 99.94% while executing our algorithm efficiently with less than 11%
      processor loads.

PMID- 24111050
TI  - Sleep phenomena as an early biomarker for Parkinsonism.
AB  - Idiopathic Rapid-Eye-Movement (REM) sleep Behavior Disorder (iRBD) is one of the
      most potential biomarkers for Parkinson's Disease (PD) and some atypical PD (AP).
      It is characterized by REM sleep with abnormal high surface EMG (sEMG) activity.
      Some twitching during REM sleep is normal, but no one has defined what normal is,
      and no well-defined methodology for measuring muscle activity in REM sleep
      exists. The purpose of this study is to investigate the possibility of detecting
      abnormal high muscle activity during REM sleep in subjects diagnosed with iRBD.
      This has been achieved by considering the abnormal high muscle activity during
      REM sleep in iRBD subjects as an outlier detection problem, while exploiting that
      iRBD muscle activity is more grouped. It was possible to correctly discriminate
      all iRBD subjects from healthy elderly control subjects and subjects diagnosed
      with periodic limb movement (PLM) disorder. However, not all PD subjects were
      classified as having abnormal muscle activity, which is assumed to support the
      fact that not all PD subjects develop RBD. 

PMID- 24111051
TI  - Automatic sleep staging: from young adults to elderly patients using multi-class
      support vector machine.
AB  - Aging is a process that is inevitable, and makes our body vulnerable to age
      related diseases. Age is the most consistent factor affecting the sleep
      structure. Therefore, new automatic sleep staging methods, to be used in both of
      young and elderly patients, are needed. This study proposes an automatic sleep
      stage detector, which can separate wakefulness, rapid-eye-movement (REM) sleep
      and non-REM (NREM) sleep using only EEG and EOG. Most sleep events, which define
      the sleep stages, are reduced with age. This is addressed by focusing on the
      amplitude of the clinical EEG bands, and not the affected sleep events. The age
      related influences are then reduced by robust subject-specific scaling. The
      classification of the three sleep stages are achieved by a multi-class support
      vector machine using the one-versus-rest scheme. It was possible to obtain a high
      classification accuracy of 0.91. Validation of the sleep stage detector in other
      sleep disorders, such as apnea and narcolepsy, should be considered in future
      work. 

PMID- 24111052
TI  - Automatic recognition of Parkinson's disease using surface electromyography
      during standardized gait tests.
AB  - Diagnosis and severity staging of Parkinsons disease (PD) relies mainly on
      subjective clinical examination. To better monitor disease progression and
      therapy success in PD patients, new objective and rater independent parameters
      are required. Surface electromyography (EMG) during dynamic movements is one
      possible modality. However, EMG signals are often difficult to understand and
      interpret clinically. In this study pattern recognition was applied to find
      suitable parameters to differentiate PD patients from healthy controls. EMG
      signals were recorded from 5 patients with PD and 5 younger healthy controls,
      while performing a series of standardized gait tests. Wireless surface electrodes
      were placed bilaterally on tibialis anterior and gastrocnemius medialis and
      lateralis. Accelerometers were positioned on both heels and used for step
      segmentation. Statistical and frequency features were extracted and used to train
      a Support Vector Machine classifier. Sensitivity and specificity were high at
      0.90 using leave-one-subject-out cross-validation. Feature selection revealed
      kurtosis and mean frequency as best features, with a significant difference in
      kurtosis (p=0.013). Evaluated on a bigger population, this could lead to
      objective diagnostic and staging tools for PD.

PMID- 24111053
TI  - Classification of ventricular arrhythmia using a support vector machine based on
      morphological features.
AB  - This paper proposes a method for the classification of ventricular arrhythmia
      using support vector machines (SVM). The features used in the SVMs were extracted
      automatically based on morphological information. Three different features were
      extracted: RR interval, QRS slope, and QRS shape similarity. Then, the SVM was
      used to classify five different electrocardiogram (ECG) heartbeat episodes. The
      Gaussian Radial Basis Function was utilized for the kernel function because the
      ECG beat episodes were treated as a non-linear pattern. The sensitivity of the
      classification used for the five beat episodes was 93.16%. 

PMID- 24111054
TI  - Parameterized SVM for personalized drug concentration prediction.
AB  - This paper proposes a parameterized Support Vector Machine (ParaSVM) approach for
      modeling the Drug Concentration to Time (DCT) curves. It combines the merits of
      Support Vector Machine (SVM) algorithm that considers various patient features
      and an analytical model that approximates the predicted DCT points and enables
      curve calibrations using occasional real Therapeutic Drug Monitoring (TDM)
      measurements. The RANSAC algorithm is applied to construct the parameter library
      for the relevant basis functions. We show an example of using ParaSVM to build
      DCT curves and then calibrate them by TDM measurements on imatinib case study. 

PMID- 24111055
TI  - Detection of a sleep disorder predicting Parkinson's disease.
AB  - Idiopathic rapid eye-movement (REM) sleep behavior disorder (iRBD) has been found
      to be a strong early predictor for later development into Parkinson's disease
      (PD). iRBD is diagnosed by polysomnography but the manual evaluation is
      laborious, why the aims of this study are to develop supportive methods for
      detecting iRBD from electroencephalo-graphic (EEG) signals recorded during REM
      sleep. This method classified subjects from their EEG similarity with the two
      classes iRBD patients and control subjects. The feature sets used for classifying
      subjects were based on the relative powers of the EEG signals in different
      frequency bands. The classification was based on the fast and classical K-means
      and Bayesian classifiers. With a subject-specific re-scaling of the feature set
      and the use of a Bayesian classifier the performance reached 90% in both
      sensitivity and specificity. For the purpose of reducing the feature count, the
      features were evaluated with the statistical Smith-Satterthwaite test and by
      using sequential forward selection a well-performing feature subset was found
      which contained only five features, while attaining a sensitivity and a
      specificity of both 80 %. 

PMID- 24111056
TI  - Shift invariant feature extraction for sEMG-based speech recognition with
      electrode grid.
AB  - For Japanese vowel recognition based on surface electromyography (sEMG), an
      electrode grid has been shown to be effective in our previous studies. In this
      study, we aim to leverage potential of the electrode grid further by using with a
      spatial shift invariant feature extraction method that can compensate deviation
      of the attached site of the electrode grid. We verified efficiency of the shift
      invariant feature extraction method in improving the recognition accuracy. 2-D
      dual tree complex wavelet transform was employed as such a shift invariant
      feature extraction method. Our result shows that shift invariant feature can
      provide additional information that cannot be provided when the channel signals
      are utilized independently. 

PMID- 24111057
TI  - One-class classification of temporal EEG patterns for K-complex extraction.
AB  - The purpose of this study was to detect one of the constituent brain waveforms in
      electroencephalography (EEG), the K-complex (KC). The role and significance of
      the KC include its engagement in information processing, sleep protection, and
      memory consolidation [1]. The method applies a two-step methodology in which
      first all the candidate KC waves are extracted based on fundamental morphological
      features imitating visual criteria. Subsequently each candidate wave is
      classified as KC or outlier according to its similarity to a set of different
      patterns (clusters) of annotated KCs. The different clusters are constructed by
      applying graph partitioning on the training set based on spectral clustering and
      exhibit temporal similarities in both signal and frequency content. The method
      was applied in whole-night sleep activity recorded using multiple EEG electrodes.
      Cross-validation was performed against visual scoring of singular generalized KCs
      during all sleep cycles and showed high sensitivity in KC detection. 

PMID- 24111058
TI  - Classification of oscillometric envelope shape using frequent sequence mining.
AB  - The shape of the oscillometric envelope is known to affect the accuracy of
      automatic noninvasive blood pressure (NIBP) measurement devices that use the
      oscillometric principle to determine systolic and diastolic blood pressures. This
      study proposes a novel shape classification method that uses data mining
      techniques to determine the characteristic sequences for different envelope
      shapes. The results indicate that the proposed method effectively determines the
      characteristic sequences for different subject groups. Subjects in the high-
      score group and in the low- score group tend to have an envelope with a broader
      plateau and are bell-shaped, respectively. This information about shape can be
      used for future determination of the correct algorithm for systolic and diastolic
      blood pressures determination in NIBP devices. 

PMID- 24111059
TI  - Quantifying cognitive state from EEG using phase synchrony.
AB  - Phase synchrony is a powerful amplitudeindependent measure that quantifies linear
      and nonlinear dynamics between non-stationary signals. It has been widely used in
      a variety of disciplines including neural science and cognitive psychology.
      Current time-varying phase estimation uses either the Hilbert transform or the
      complex wavelet transform of the signals. This paper exploits the concept of
      phase synchrony as a mean to discriminate face processing from the processing of
      a simple control stimulus. Dependencies between channel locations were assessed
      for two separate conditions elicited by distinct pictures (representing a human
      face and a Gabor patch), both flickering at a rate of 17.5 Hz. Statistical
      analysis is performed using the Kolmogorov-Smirnov test. Moreover, the phase
      synchrony measure used is compared with a measure of association that has been
      previously applied in the same context: the generalized measure of association
      (GMA). Results show that although phase synchrony works well in revealing regions
      of high synchronization, and therefore achieves an acceptable level of
      discriminability, this comes at the expense of sacrificing time resolution. 

PMID- 24111060
TI  - Early detection of cognitive impairment in the elderly based on Bayesian mining
      using speech prosody and cerebral blood flow activation.
AB  - With the aim of providing computer aided diagnosis of dementia, we have developed
      a non-invasive screening system of the elderly with cognitive impairment. In our
      previous research, we have studied two data-mining approaches by focusing on
      speech-prosody and cerebral blood flow (CBF) activation during cognitive tests.
      On the power of these research results, this paper presents a prosody-CBF hybrid
      screening system of the elderly with cognitive impairment based on a Bayesian
      approach. The system is constructed by SPCIR (Speech Prosody-Based Cognitive
      Impairment Rating) based cutoff as the 1st screening, and, as the 2nd screening,
      two-phase Bayesian classifier for discriminating among elderly individuals with
      three clinical groups: elderly individuals with normal cognitive abilities (NC),
      patients with mild cognitive impairment (MCI), and Alzheimer's disease (AD). This
      paper also reports the screening examination and discusses the cost-effectiveness
      and the discrimination performance of the proposed system for early detection of
      cognitive impairment in elderly subjects. 

PMID- 24111061
TI  - Protocol for site selection and movement assessment for the myoelectric control
      of a multi-functional upper-limb prosthesis.
AB  - Although there have been many advances in electromyography (EMG) signal
      processing and pattern recognition (PR) for the control of multi-functional upper
      limb prostheses, some the outstanding problems need to be solved before practical
      PR-based prostheses can be put into service. Some of these are the lack of
      training and deployment protocols and the provision of the tools required.
      Therefore, we present a preliminary procedure to personalize the prosthesis
      deployment. In the first step, we record the demographic information of each
      individual amputee person and their background. In the second step of the
      protocol, the EMG signals are acquired. PR algorithms and parameters will be
      chosen in the 3(rd) step of the protocol. In the 4(th) step, the best number of
      EMG sensors to achieve the maximal performance with a full set of gestures is
      identified. The final step involves finding the best set of movements that the
      amputee person can produce with an accuracy > 95% as well as identifying the
      movements with the worst performance, which would require further training. This
      proposed approach is validated with 2 transradial amputees. 

PMID- 24111062
TI  - Noninvasive prediction of catheter ablation acute outcome in persistent atrial
      fibrillation based on logistic regression of ECG fibrillatory wave amplitude and
      spatio-temporal variability.
AB  - Catheter ablation (CA) is increasingly employed to treat persistent atrial
      fibrillation (AF), yet assessment of procedural AF termination is still a subject
      of debate in the medical community. This has motivated the development of
      different criteria based on the standard electrocardiogram (ECG) to characterize
      ablation immediate effectiveness. However, most of conventional descriptors are
      merely computed in one ECG lead, thus neglecting significant information provided
      by the other leads. The present study proposes a novel predictor of CA outcome by
      exploiting a subset of the 12 leads in the standard ECG. Our method predicts the
      need for electrical cardioversion subsequent to CA by suitably combining two sets
      of multilead features, namely, a measure of fibrillatory wave amplitude and an
      index of AF spatio-temporal variability per lead. These features are obtained on
      a reduced-rank approximation determined by principal component analysis
      emphasizing the highest-variance components in the multilead atrial activity
      signal, and are then combined by logistic regression. On a database of over 50
      persistent AF patients, our method provides reliable predictive measures and
      proves more robust and informative than classical AF descriptors. 

PMID- 24111063
TI  - Multivariate assessment of differences between a neuromuscular electrical
      stimulation therapy and robotic treadmill training in the rehabilitation of
      spinal cord injured rats.
AB  - A study was conducted to evaluate and compare the effects of two different
      rehabilitation therapies on spinal cord injured (SCI) rats: neuromuscular
      electrical stimulation which is timed to robotic treadmill training (NMES+RTT)
      and RTT alone. Several electromyography (EMG) based variables were measured, but
      most did not change significantly after treatment, contrary to observations of
      overall qualitative stepping ability. However, when the variables are viewed in
      multi-dimensional space, there are visible differences between changes after
      NMES+RTT vs. those after RTT only. Principal component analysis (PCA) and k-means
      clustering were applied to the multivariate data. The data in principal component
      space was significantly separated, according to the Euclidean distance. PCA also
      provided a straightforward tool for selecting which combination of measures to
      compare. The measures which best separated out the differences between NMES+RTT
      and RTT were percentage of steps associated with bursts, burst-to-step latency,
      and the standard deviation of this latency, even though these measures did not
      always show the greatest statistical significance individually. Thus, the
      rehabilitative effects of NMES+RTT are not necessarily reflected in individual
      EMG measures, but rather in a combination of the measures representing a multi
      dimensional space. 

PMID- 24111064
TI  - A single-trial toolbox for advanced sleep polysomnographic preprocessing.
AB  - The application of polysomnographic (PSG) studies for monitoring sleep activity
      is a multi-parametric practice that involves a diverse group of biological
      signals. A suitable preprocessing of such signals assures a more profitable
      feature extraction and classification operations. Therefore, the proposed
      preprocessing toolbox performs segmentation, filtering, denoising, whitening and
      artefact removal tasks upon multi-channel PSG recordings. In order to assess
      toolbox's efficiency, clinical experiments are conducted, as well as,
      quantitative and qualitative metrics are discussed. Our findings reveal
      outperforming efficiency by artefacts and noise rejection after single-trial and
      multi-stage preprocessing. 

PMID- 24111065
TI  - Blind source separation in characterizing ECG pre-shock waveforms during
      Ventricular Fibrillation.
AB  - Ventricular Fibrillation (VF) is a cardiac arrhythmia for which the only
      available treatment option is defibrillation by electrical shock. Existing
      literature indicates that VF could be the manifestation of different sources
      controlling the heart with different degrees of organization. In this work we
      test the hypothesis that the pre-shock waveforms of successful and unsuccessful
      shock outcomes could be related to the number of independent sources present in
      these waveforms. The proposed method uses Blind Source Separation (BSS) to
      extract independent components in frequency direction from a pig database
      consisting of 20 pre-shock waveforms. The slope of the energy capture curve was
      used as an indicator to demonstrate the number of independent sources required to
      model the pre-shock waveforms. The results were also quantified by performing a
      linear discriminant analysis based classification achieving an overall
      classification accuracy of 75%. The results indicate that successful cases can be
      modeled with less number of independent sources compared to unsuccessful cases. 

PMID- 24111066
TI  - Blind source separation of neural activities from magnetoencephalogram in
      periodical median nerve stimuli.
AB  - Neural activities of cortices in periodical median nerve stimuli are studied from
      magnetoencephalogram. The fractional type of the decorrelation method is used for
      the blind source separation with temporal structure. The blind source separation
      method is proposed for selecting neural activities related to somatosensory
      stimulus from magnetoencephalogram by comparing cross-correlation functions
      between components of blind source separation. 

PMID- 24111067
TI  - Eliminating cardiac electrical artifacts from cardiac autonomic nervous signals
      using a combination of empirical mode decomposition and independent component
      analysis.
AB  - Cardiac autonomic nervous (CAN) signals in ambulatory dogs can nowadays be
      measured by an implantable radio transmitter system. CAN signals are known to be
      related to heart failure. However, they are critically contaminated by cardiac
      electrical activities (CEA) which confound data analysis. We propose a method of
      analysis which combines empirical mode decomposition (EMD) and independent
      component analysis (ICA). This method composed of two steps: First, the EMD
      method decomposed a single channel recording into multichannel data, then we
      applied the ICA to these multichannel data. Using an ambulatory dog's CAN signal
      data from Seoul National University Hospital, we compared our approach with a
      commonly used high pass filter (HPF) method for various amplitudes of simulated
      CAN signals. Root-mean-squared errors between simulated CAN signals and CAN
      signals with CEA artifact were calculated for assessing the noise cancellation
      effect. Moreover, we observed changes in spectral content via power spectral
      density. Finally, we applied the proposed method to real data. Our method could
      not only extract and remove CEA artifact in CAN signals, but also preserved the
      spectral content of CAN signals. 

PMID- 24111068
TI  - EyeCatch: data-mining over half a million EEG independent components to construct
      a fully-automated eye-component detector.
AB  - Independent component analysis (ICA) can find distinct sources of
      electroencephalographic (EEG) activity, both brain-based and artifactual, and has
      become a common pre-preprocessing step in analysis of EEG data. Distinction
      between brain and non-brain independent components (ICs) accounting for, e.g.,
      eye or muscle activities is an important step in the analysis. Here we present a
      fully automated method to identify eye-movement related EEG components by
      analyzing the spatial distribution of their scalp projections (scalp maps). The
      EyeCatch method compares each input scalp map to a database of eye-related IC
      scalp maps obtained by data-mining over half a million IC scalp maps obtained
      from 80,006 EEG datasets associated with a diverse set of EEG studies and
      paradigms. To our knowledge this is the largest sample of IC scalp maps that has
      ever been analyzed. Our result show comparable performance to a previous state-of
      art semi-automated method, CORRMAP, while eliminating the need for human
      intervention. 

PMID- 24111069
TI  - Decomposing atrial activity signal by combining ICA and WABS.
AB  - In this paper we proposed a novel technique for Atrial Activity (AA)
      decomposition in Electrocardiogram (ECG) of Atrial Fibrillation (AF). The main
      purpose of our proposed technique is to decompose AA signal by combining two
      statistical methods, Independent Component Analysis (ICA)-existing and Weighted
      Average Beat Subtraction (WABS)-new, for AF with multiple stable sources,
      respectively. We found the limits of BSS algorithms which are mostly used to
      extract AA signal, while beauty of our proposed algorithm is that it decomposes
      multi-lead AA signals from surface ECG with AF. Our proposed technique is
      verified with clinical data and the results demonstrate that our proposed method
      is feasible. 

PMID- 24111070
TI  - An automatic electroencephalography blinking artefact detection and removal
      method based on template matching and ensemble empirical mode decomposition.
AB  - Electrooculographic (EOG) artefacts are one of the most common causes of
      Electroencephalogram (EEG) distortion. In this paper, we propose a method for EOG
      Blinking Artefacts (BAs) detection and removal from EEG. Normalized Correlation
      Coefficient (NCC), based on a predetermined BA template library was used for
      detecting the BA. Ensemble Empirical Mode Decomposition (EEMD) was applied to the
      contaminated region and a statistical algorithm determined which Intrinsic Mode
      Functions (IMFs) correspond to the BA. The proposed method was applied in
      simulated EEG signals, which were contaminated with artificially created EOG BAs,
      increasing the Signal-to-Error Ratio (SER) of the EEG Contaminated Region (CR) by
      35 dB on average.

PMID- 24111072
TI  - Self-assessment for optic disc segmentation.
AB  - Optic disc segmentation from retinal fundus image is a fundamental but important
      step in many applications such as automated glaucoma diagnosis. Very often, one
      method might work well on many images but fail on some other images and it is
      difficult to have a single method or model to cover all scenarios. Therefore, it
      is important to combine results from several methods to minimize the risk of
      failure. For this purpose, this paper computes confidence scores for three
      methods and combine their results for an optimal one. The experimental results
      show that the combined result from three methods is better than the results by
      any individual method. It reduces the mean overlapping error by 7.4% relatively
      compared with best individual method. Simultaneously, the number of failed cases
      with large overlapping errors is also greatly reduced. This is important to
      enhance the clinical deployment of the automated disc segmentation. 

PMID- 24111073
TI  - Automated quantification of retinal arteriovenous nicking from colour fundus
      images.
AB  - Retinal arteriovenous nicking (AV nicking) is the phenomenon where the venule is
      compressed or decreases in its caliber at both sides of an arteriovenous
      crossing. Recent research suggests that retinal AVN is associated with
      hypertension and cardiovascular diseases such as stroke. In this article, we
      propose a computer method for assessing the severity level of AV nicking of an
      artery-vein (AV) crossing in color retinal images. The vascular network is first
      extracted using a method based on multi-scale line detection. A trimming process
      is then performed to isolate the main vessels from unnecessary structures such as
      small branches or imaging artefact. Individual segments of each vessel are then
      identified and the vein is recognized through an artery-vein identification
      process. A vessel width measurement method is devised to measure the venular
      caliber along its two segments. The vessel width measurements of each venular
      segment is then analyzed and assessed separately and the final AVN index of a
      crossover is computed as the most severity of its two segments. The proposed
      technique was validated on 69 AV crossover points of varying AV nicking levels
      extracted from retinal images of the Singapore Malay Eye Study (SiMES). The
      results show that the computed AVN values are highly correlated with the manual
      grading with a Spearman correlation coefficient of 0.70. This has demonstrated
      the accuracy of the proposed method and the feasibility to develop a computer
      method for automatic AV nicking detection. The quantitative measurements provided
      by the system may help to establish a more reliable link between AV nicking and
      known systemic and eye diseases, which deserves further examination and
      exploration. 

PMID- 24111074
TI  - Automated segmentation of the choroid in retinal optical coherence tomography
      images.
AB  - The choroid is a tissue layer at the back of the eye, which can be imaged by
      optical coherence tomography (OCT). Choroidal thickness has been proven to be
      correlated to several ophthalmic diseases in several studies. In this paper we
      proposed a novel segmentation technique to address this challenge. This technique
      firstly automatically segments the inner boundary of the choroid using a two
      stage fast active contour model. It secondly allows a real-time human-supervised
      automated segmentation on the outer boundary of the choroid. Dice similarity
      coefficient (DSC) was used to evaluate the agreement between manual annotation
      and our automated measurements on 30 images captured from patients diagnosed with
      diabetes. The mean DSC value is 92.7% (standard deviation 3.6%) in the range of
      85.5% to 98.1%. Results show that this new technique can achieve choroid
      segmentation with high accuracy. 

PMID- 24111075
TI  - Automated microaneurysm detection method based on Eigenvalue analysis using
      Hessian matrix in retinal fundus images.
AB  - Diabetic retinopathy (DR) is the most frequent cause of blindness. Microaneurysm
      (MA) is an early symptom of DR. Therefore, the detection of MA is important for
      the early detection of DR. We have proposed an automated MA detection method
      based on double-ring filter, but it has given many false positives. In this
      paper, we propose an MA detection method based on eigenvalue analysis using a
      Hessian matrix, with an aim to improve MA detection. After image preprocessing,
      the MA candidate regions were detected by eigenvalue analysis using the Hessian
      matrix in green-channeled retinal fundus images. Then, 126 features were
      calculated for each candidate region. By a threshold operation based on feature
      analysis, false positive candidates were removed. The candidate regions were then
      classified either as MA or false positive using artificial neural networks (ANN)
      based on principal component analysis (PCA). The 126 features were reduced to 25
      components by PCA, and were then inputted to ANN. When the method was evaluated
      on visible MAs using 25 retinal images from the retinopathy online challenge
      (ROC) database, the true positive rate was 73%, with eight false positives per
      image. 

PMID- 24111076
TI  - 3D optic disc reconstruction via a global fundus stereo algorithm.
AB  - This paper presents a novel method to recover 3D structure of the optic disc in
      the retina from two uncalibrated fundus images. Retinal images are commonly
      uncalibrated when acquired clinically, creating rectification challenges as well
      as significant radiometric and blur differences within the stereo pair. By
      exploiting structural peculiarities of the retina, we modified the Graph Cuts
      computational stereo method (one of current state-of-the-art methods) to yield a
      high quality algorithm for fundus stereo reconstruction. Extensive qualitative
      and quantitative experimental evaluation (where OCT scans are used as 3D ground
      truth) on our and publicly available datasets shows the superiority of the
      proposed method in comparison to other alternatives.

PMID- 24111077
TI  - Super-image mosaic of infant retinal fundus: selection and registration of the
      best-quality frames from videos.
AB  - Wide-field retinal fundus cameras are commercially available devices that allow
      acquiring videos of a wide area of infants' eye, considered of clinical interest
      in screening for ROP (Retinopathy of Prematurity). Many frames of the video are
      often altered by defects such as artifacts, interlacing and defocus, which make
      critical and time consuming the search and choice of the good frames to be
      analyzed. We developed a computerized system that automatically selects the best
      still frames from the video and builds a mosaic from these images. It will allow
      clinicians to examine a single large, best quality image. The best frames are
      identified using several image quality parameters that measure sharpness and
      steadiness, and then registered to obtain a single mosaic image. A custom
      blending procedure is then applied in order to provide a final image with
      homogeneous luminosity and contrast, devoid of the dark areas typically present
      in the outer regions of single frames. The best-frame selection module showed a
      PPV of 0.92, while the visual inspection of resulting mosaics confirmed the
      remarkable capability of the proposed system to provide higher quality images. 

PMID- 24111078
TI  - Automatic screening of narrow anterior chamber angle and angle-closure glaucoma
      based on slit-lamp image analysis by using support vector machine.
AB  - At present, Van Herick's method is a standard technique used to screen a Narrow
      Anterior Chamber Angle (NACA) and Angle-Closure Glaucoma (ACG). It can identify a
      patient who suffers from NACA and ACG by considering the width of peripheral
      anterior chamber depth (PACD) and corneal thickness. However, the screening
      result of this method often varies among ophthalmologists. So, an automatic
      screening of NACA and ACG based on slit-lamp image analysis by using Support
      Vector Machine (SVM) is proposed. SVM can automatically generate the
      classification model, which is used to classify the result as an angle-closure
      likely or an angle-closure unlikely. It shows that it can improve the accuracy of
      the screening result. To develop the classification model, the width of PACD and
      corneal thickness from many positions are measured and selected to be features. A
      statistic analysis is also used in the PACD and corneal thickness estimation in
      order to reduce the error from reflection on the cornea. In this study, it is
      found that the generated models are evaluated by using 5-fold cross validation
      and give a better result than the result classified by Van Herick's method. 

PMID- 24111079
TI  - Comparison of logistic regression and neural network classifiers in the detection
      of hard exudates in retinal images.
AB  - Diabetic Retinopathy (DR) is a common cause of visual impairment in
      industrialized countries. Automatic recognition of DR lesions in retinal images
      can contribute to the diagnosis and screening of this disease. The aim of this
      study is to automatically detect one of these lesions: hard exudates (EXs). Based
      on their properties, we extracted a set of features from image regions and
      selected the subset that best discriminated between EXs and the retinal
      background using logistic regression (LR). The LR model obtained, a multilayer
      perceptron (MLP) classifier and a radial basis function (RBF) classifier were
      subsequently used to obtain the final segmentation of EXs. Our database contained
      130 images with variable color, brightness, and quality. Fifty of them were used
      to obtain the training examples. The remaining 80 images were used to test the
      performance of the method. The highest statistics were achieved for MLP or RBF.
      Using a lesion based criterion, our results reached a mean sensitivity of 95.9%
      (MLP) and a mean positive predictive value of 85.7% (RBF). With an image-based
      criterion, we achieved a 100% mean sensitivity, 87.5% mean specificity and 93.8%
      mean accuracy (MLP and RBF). 

PMID- 24111080
TI  - A novel wearable laser device to regulate stride length in Parkinson's disease.
AB  - Decreased stride length is a highly relevant characteristic of the gait in
      patients with Parkinson's disease (PD). In this paper, a novel wearable laser
      device for stride length regulation is presented. The device is mounted to one
      foot and can project a red laser light strip to the floor as a visual cue for the
      other foot. In the experiment twelve healthy volunteers walked a 20 m straight
      walkway wearing the system on both feet. As an objective result, the stride
      length regulation reached an accuracy of 96.1 +/- 2.5 (94.0 +/- 3.5) % for a pre
      defined stride length lambdadef= 55 (65) cm. The subjective evaluation by the
      participants using a questionnaire revealed that the visual cue projected from
      the laser device was considered a stable signal that did not shake during
      walking. 6 of 12 participants felt that this device was not interfering with
      their gait, 3 of 12 judged this aspect neutrally, and 3 of 12 considered it
      somehow bothersome.

PMID- 24111081
TI  - Development of multichannel array transducer of displacement mechanical-myogram.
AB  - The myoelectric signal (EMG) recorded on the skin surface is a time-related and
      spatial aggregate of the action potentials of motor units of skeletal muscle, and
      it indicates the input information for muscle contraction. The mechano-myographic
      signal (MMG) is a vibration of skin/muscle surface caused by muscle contraction
      and it directly reflects the activity of muscle contraction. The two-dimensional
      generation mechanism of MMG is still n ot clarified in detail. In this study, the
      displacement MMGs were recorded at 25 measuring points using 5 * 5 displacement
      MMG array transducer within 50* 50 mm, while the motor point of the biceps
      brachii was electro-stimulated. The spatial propagation map of twitch waveform of
      displacement MMG was drawn.

PMID- 24111082
TI  - Coordinated upper limb training assisted with an electromyography (EMG)-driven
      hand robot after stroke.
AB  - An electromyography (EMG)-driven hand robot had been developed for post-stroke
      rehabilitation training. The effectiveness of the hand robot assisted whole upper
      limb training on muscular coordination was investigated on persons with chronic
      stroke (n=10) in this work. All subjects attended a 20-session training (3-5
      times/week) by using the hand robot to practice object grasp/release and arm
      transportation tasks. Improvements were found in the muscle co-ordination between
      the antagonist muscle pair (flexor digitorum and extensor digitorum) as measured
      by muscle co-contractions in EMG signals; and also in the reduction of excessive
      muscle activities in the biceps brachii. Reduced spasticity in the fingers was
      also observed as measured by the Modified Ashworth Score. 

PMID- 24111083
TI  - A method for shoulder range-of-motion estimation using a single wireless sensor
      node.
AB  - This study proposes a method for range-of-motion (ROM) estimation based on the
      acceleration and geomagnetic data acquired using a single miniaturized wireless
      sensor node. An experiment on eight shoulder rehabilitation protocols in real
      human subjects has been conducted, with a sensor placed on user's left and right
      upper arms and wrists. The experimental results demonstrate the limitations of
      estimation methods that use sensors placed on skin surface and that, despite
      being a different body segment, the wrist is a better placement position for
      sensor-based shoulder joint ROM measurement than the shoulder itself. 

PMID- 24111084
TI  - Mapping sensor activation time for typing tasks performed with a tongue
      controlled oral interface.
AB  - Two tetraplegic subjects performed typing tasks on a computer in an experiment
      using a tongue controlled oral interface. This paper reports mapping of the
      sensor activation time for a full alphabet text input using 10 inductive sensors.
      A small cylindrical piece of soft ferromagnetic material activated the sensors
      when placed at or glided along the surface of the sensor. The activation unit was
      attached to the tongue as the upper ball of a piercing. The tasks consisted of
      typing characters according to ordered (rows and columns) or random test strings
      during 30 seconds, with and without deleting characters typed by mistake. Visual
      feedback assisted the subjects to perform the typing tasks. Average activation
      times were of 0.82+/-0.38 and 1.06 +/-0.27 seconds respectively for the two
      subjects. Analysis of activation times may be useful in characterization of the
      tongue ability to activate the interface as well as in design optimization of the
      layout of the sensors. 

PMID- 24111085
TI  - Biofeedback baropodometry training evaluation: a study with children with equinus
      foot deformity.
AB  - The lack of perception in the hindfoot increases the plantar flexion, causing
      irregular posture due to the foot position, a disability known as equinus foot
      deformity. A portable device, named baropodometer, that measures the pressure at
      the forefoot and hindfoot regions was built to help this population in terms of
      balance and posture correction. Ten hemiparetic teenager volunteers with equinus
      foot participated in the experiments. The results demonstrated that the proposed
      device increased the weight-bearing in upright stance in the paretic side,
      decreasing the weight in the non-paretic side. After 10 experimental sessions,
      performed along 6 months, the distribution of the pressure in the lower limbs was
      very similar. The baropodometer facilitates the rehabilitation, by biofeedbacking
      the pressure of the calcaneus, using the volunteer's audiovisual system. The
      rehabilitation using the proposed device was able to recover the balance by
      posture correction, facilitating future gait training of these volunteers. 

PMID- 24111086
TI  - Pattern recognition based forearm motion classification for patients with chronic
      hemiparesis.
AB  - To make full use of electromyography (EMG) that contains rich information of
      muscular activities in active rehabilitation for motor hemiparetic patients, a
      couple of recent studies have explored the feasibility of applying pattern
      recognition technique to the classification of multiple motion classes for stroke
      survivors and reported some promising results. However, it still remains unclear
      if kinematics signals could also bring good motion classification performance,
      particularly for patients after traumatic brain damage. In this study, the
      kinematics signals was used for motion classification analysis in three stroke
      survivors and two patients after traumatic brain injury, and compared with EMG.
      The results showed that an average classification error of 7.9 +/- 6.8% for the
      affected arm over all subjects could be achieved with a linear classifier when
      they performed multiple fine movements, 7.9% lower than that when using EMG. With
      either kind of signals, the motor control ability of the affected arm degraded
      significantly in comparison to the intact side. The preliminary results suggested
      the great promise of kinematics information as well as the biological signals in
      detecting user's conscious effort for robot-aided active rehabilitation.

PMID- 24111087
TI  - Generating tactile afferent stimulation patterns for slip and touch feedback in
      neural prosthetics.
AB  - Current prosthetic limbs are limited by a lack of tactile feedback. Slip feedback
      is particularly important to inform grip. Object slip is marked by both a change
      in the normal grip force applied and a change in force tangential to the
      fingertips. In this study, we demonstrate that a new multi-axial tactile sensor
      composed of gold nanoparticle strain gauges is able to record slip and
      reconstruct the X, Y, and Z forces incident on the sensor's surface due to a
      slipping object. We entered the X, Y, and Z force components generated by the
      slip event into a noisy leaky integrate and fire model to simulate the firing
      responses of SA1 and FA1 afferents. We also recorded a uniaxial normal force
      input representative of tactile contact. A single set of SA1 model and FA1 model
      parameters generated realistic firing patterns for both the slip and normal force
      recordings. These results suggest that canonical SA1 and FA1 afferent models
      could be used to generate biomimetic electrical stimulation patterns for both
      slip and touch stimuli. When used to activate the tactile afferents of an
      amputee, these electrical stimulation patterns could create natural and
      distinguishable slip and touch percepts for closed loop control of an upper limb
      neural prosthesis. 

PMID- 24111088
TI  - Real-time implementation of a self-recovery EMG pattern recognition interface for
      artificial arms.
AB  - EMG pattern classification has been widely studied for decoding user intent for
      intuitive prosthesis control. However, EMG signals can be easily contaminated by
      noise and disturbances, which may degrade the classification performance. This
      study aims to design a real-time self-recovery EMG pattern classification
      interface to provide reliable user intent recognition for multifunctional
      prosthetic arm control. A novel self-recovery module consisting of multiple
      sensor fault detectors and a fast LDA classifier retraining strategy has been
      developed to immediately recover the classification performance from signal
      disturbances. The self-recovery EMG pattern recognition (PR) system has been
      implemented on an embedded system as a working prototype. Experimental evaluation
      has been performed on an able-bodied subject in real-time to classify three arm
      movements while signal disturbances were manually introduced. The results of this
      study may propel the clinical use of EMG PR for multifunctional prosthetic arm
      control. 

PMID- 24111089
TI  - Sparse Bayesian inference methods for decoding 3D reach and grasp kinematics and
      joint angles with primary motor cortical ensembles.
AB  - Sparse Bayesian inference methods are applied to decode three-dimensional (3D)
      reach to grasp movement based on recordings of primary motor cortical (M1)
      ensembles from rhesus macaque. For three linear or nonlinear models tested,
      variational Bayes (VB) inference in combination with automatic relevance
      determination (ARD) is used for variable selection to avoid overfitting. The
      sparse Bayesian linear regression model achieved the overall best performance
      across objects and target locations. We assessed the sensitivity of M1 units in
      decoding and evaluated the proximal and distal representations of joint angles in
      population decoding. Our results suggest that the M1 ensembles recorded from the
      precentral gyrus area carry more proximal than distal information. 

PMID- 24111090
TI  - Computational models of optogenetic tools for controlling neural circuits with
      light.
AB  - Optogenetics is a new neurotechnology innovation based on the creation of light
      sensitivity of neurons using gene technologies and remote light activation.
      Optogenetics allows for the first time straightforward targeted neural
      stimulation with practically no interference between multiple stimulation points
      since either light beam can be finely confined or the expression of light
      sensitive ion channels and pumps can be genetically targeted. Here we present a
      generalised computational modeling technique for various types of optogenetic
      mechanisms, which was implemented in the NEURON simulation environment. It was
      demonstrated on the example of a two classical mechanisms for cells optical
      activation and silencing: channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR).We
      theoretically investigate the dynamics of the neural response of a layer 5
      cortical pyramidal neuron (L5) to four different types of illuminations: 1) wide
      field whole cell illumination 2) wide-field apical dendritic illumination 3)
      focal somatic illumination and 4) focal axon initial segment (AIS) illumination.
      We show that whole-cell illumination of halorhodopsin most effectively
      hyperpolarizes the neuron and is able to silence the cell even when driving input
      is present. However, when channelrhodopsin-2 and halorhodopsin are concurrently
      active, the relative location of each illumination determines whether the
      response is modulated with a balance towards depolarization. The methodology
      developed in this study will be significant to interpret and design optogenetic
      experiments and in the field of neuroengineering in general. 

PMID- 24111091
TI  - Event-related potential study on image-symmetry discrimination in the human
      brain.
AB  - The human visual system seems to have a highly perceptual sensitivity to
      symmetry. However, where and when the discrimination of symmetrical properties
      begins in the context of visual information processing is largely unclear. This
      study investigates event-related potential (ERP) patterns in humans when
      perceiving symmetry-varied complex object images. ERP responses were derived from
      electroencephalography (EEG) data recorded from eight healthy subjects using 128
      channel scalp electrodes. Visual stimulation was provided using gray-scaled
      photographs of a car with six different viewpoints, hence disrupting the vertical
      symmetry, where one of the stimuli was intentionally made symmetric by mirroring
      the image about its center vertical axis. The results show that discrimination of
      image symmetry is revealed by potential deflection in early ERP components
      recorded at occipito-temporal sites and can be significantly observed around 220
      ms after stimulus onset. 

PMID- 24111092
TI  - A neural mass model of spontaneous burst suppression and epileptic seizures.
AB  - The paper presents a neural mass model that is capable of simulating the
      transition to and from various forms of paroxysmal activity such as burst
      suppression and epileptic seizure-like waveforms. These events occur without
      changing parameters in the model. The model is based on existing neural mass
      models, with the addition of feedback of fast dynamics to create slowly time
      varying parameters, or slow states. The goal of this research is to establish a
      link between system properties that modulate neural activity and the fast
      changing dynamics, such as membrane potentials and firing rates that can be
      manipulated using electrical stimulation. Establishing this link is likely to be
      a necessary component of a closed-loop system for feedback control of
      pathological neural activity. 

PMID- 24111093
TI  - Internal inconsistencies in models of electrical stimulation in neural tissue.
AB  - Calculating the membrane potential of a neurite under extracellular electrical
      stimulation is important in the design of some recent stimulation strategies for
      neuroprosthetic devices including retinal implants, cochlear implants, deep brain
      stimulation. A common approach, widely used in the electrical stimulation
      literature uses a volume conductor model to calculate the electrical potential in
      the tissue and then extracts the voltage or current density on the surface of a
      neuron, which is used as input to the cable equation to calculate the neuron's
      response. However this approach ignores the effect of the neuron itself as well
      as surrounding neurons on the extracellular potential. Here we highlight that
      this leads to an internal inconsistency in the overall model because the result
      depends on whether the voltage or current density is used to calculate the neural
      response. The magnitude of this discrepancy is calculated for the example of a
      point source electrode in a homogeneous medium and is shown to be up to several
      hundred percent under some stimulus conditions. The inconsistency can be resolved
      by ensuring that the voltage is related to the current density by the
      transimpedance of the neurite. Deriving a volume conductor model that satisfies
      this relationship requires further work. 

PMID- 24111094
TI  - The role of topography in the transformation of spatiotemporal patterns by a
      large-scale, biologically realistic model of the rat dentate gyrus.
AB  - A large-scale, biologically realistic, computational model of the rat hippocampus
      is being constructed to study the input-output transformation that the
      hippocampus performs. In the initial implementation, the layer II entorhinal
      cortex neurons, which provide the major input to the hippocampus, and the granule
      cells of the dentate gyrus, which receive the majority of the input, are modeled.
      In a previous work, the topography, or the wiring diagram, connecting these two
      populations had been derived and implemented. This paper explores the
      consequences of two features of the topography, the distribution of the axons and
      the size of the neurons' axon terminal fields. The topography converts streams of
      independently generated random Poisson trains into structured spatiotemporal
      patterns through spatiotemporal convergence achievable by overlapping axon
      terminal fields. Increasing the axon terminal field lengths allowed input to
      converge over larger regions of space resulting in granule activation across a
      greater area but did not increase the total activity as a function of time as the
      number of targets per input remained constant. Additional simulations
      demonstrated that the total distribution of spikes in space depends not on the
      distribution of the presynaptic axons but the distribution of the postsynaptic
      population. Analyzing spike counts emphasizes the importance of the postsynaptic
      distribution, but it ignores the fact that each individual input may be carrying
      unique information. Therefore, a metric should be created that relates and tracks
      individual inputs as they are propagated and integrated through hippocampus. 

PMID- 24111095
TI  - Conformal ceramic electrodes that record glutamate release and corresponding
      neural activity in primate prefrontal cortex.
AB  - Conformal ceramic electrodes utilized in prior recordings of nonhuman primate
      prefrontal cortical layer 2/3 and layer 5 neurons were used in this study to
      record tonic glutamate concentration and transient release in layer 2/3 PFC.
      Tonic glutamate concentration increased in the Match (decision) phase of a visual
      delayed-match-to-sample (DMS) task, while increased transient glutamate release
      occurred in the Sample (encoding) phase of the task. Further, spatial vs. object
      oriented DMS trials evoked differential changes in glutamate concentration. Thus
      the same conformal recording electrodes were capable of electrophysiological and
      electrochemical recording, and revealed similar evidence of neural processing in
      layers 2/3 and layer 5 during cognitive processing in a behavioral task. 

PMID- 24111096
TI  - Modeling analysis of negative effects of high frequency electrical stimulation on
      axonal behaviors.
AB  - High frequency biphasic (HFB) electrical stimulation were commonly used in nerve
      block. This study constructed a double layer amphibian axonal model to explore
      the negative effects possibly caused by HFB electrical stimulation. The model was
      based on Frankenhaeuser-Huxley (FH) equations and McIntyre-Richardson-Grill (MRG)
      model geometry parameters. Sodium pump and ionic diffusion mechanisms for sodium,
      potassium, and chloride ions were included. HFB electrical stimulation of 10 kHz
      at 5 mA was applied for 5 s at half the axonal length. The action potentials
      recorded at node three fourth of axonal length exhibited larger delays, smaller
      amplitudes and more positive pre-occurring resting potentials than normal ones.
      Changes of intracellular ionic concentrations were observed and considered as one
      main mechanism underlying the axonal behavior changes induced by HFB electrical
      stimulation. This study provides useful information about mechanism of nerve
      injury caused by HFB electrical blocking stimulation. 

PMID- 24111097
TI  - The contribution of relative activation levels between populations of cells to
      network activity in a large-scale biologically realistic model of the
      hippocampus.
AB  - In previously published work, we showed the progress we've made towards creating
      a large-scale, biologically realistic model of the rat hippocampus, starting with
      the projection from entorhinal cortex (EC) to the dentate gyrus (DG). We created
      the model to help us study how the common components of neurobiological systems
      in mammals - large numbers of neurons with intricate, branching morphologies;
      active, non-linear membrane properties; nonuniform distributions throughout
      membrane surface of these non-linear conductances; non-uniform and topographic
      connectivity between pre- and post-synaptic neurons; and activity-dependent
      changes in synaptic function - combine and contribute to give a particular brain
      region its "neural processing" properties. In this work, we report on the results
      of a series of simulations we ran to test the role of feed-forward and feedback
      inhibition in the dentate gyrus. We find that a) the system shows rhythmic bands
      of activity only in the presence of feedback inhibition, b) that the frequency of
      rhythmicity increases with increasing amounts of feed-forward inhibition, c) that
      it decreases with increasing amounts of feedback inhibition, and d) that strong
      excitatory inputs appear to enhance and prolong the amount of rhythmicity in the
      system. 

PMID- 24111098
TI  - A neuronal network model with simplified tonotopicity for tinnitus generation and
      its relief by sound therapy.
AB  - Tinnitus is the perception of sound in the ears or in the head where no external
      source is present. Sound therapy is one of the most effective techniques for
      tinnitus treatment that have been proposed. In order to investigate mechanisms of
      tinnitus generation and the clinical effects of sound therapy, we have proposed
      conceptual and computational models with plasticity using a neural oscillator or
      a neuronal network model. In the present paper, we propose a neuronal network
      model with simplified tonotopicity of the auditory system as more detailed
      structure. In this model an integrate-and-fire neuron model is employed and
      homeostatic plasticity is incorporated. The computer simulation results show that
      the present model can show the generation of oscillation and its cessation by
      external input. It suggests that the present framework is promising as a modeling
      for the tinnitus generation and the effects of sound therapy. 

PMID- 24111099
TI  - Reduction of metallic interference in MEG signals using AMUSE.
AB  - Magnetoencephalography is a technique that can noninvasively measure the brain
      signal. There are many advantages of using this technique rather than similar
      procedures such as the EEG for the evaluation of medical diseases. However, one
      of its main problems is its high sensitivity to sources causing metallic
      distortion of the signal, and the removal of this type of artifacts remains
      unsolved. In this study a technique for reducing metallic interference was
      presented. This algorithm was based on AMUSE, a second order blind source
      separation method, and a procedure for choosing the artifactual independent
      components was also presented. The results showed that the elimination of these
      artifacts would be possible by means of the application of this AMUSE-based
      interference reduction procedure.

PMID- 24111100
TI  - Information theoretic optimization of cochlear implant electrode usage
      probabilities.
AB  - Cochlear implants are neural prostheses that can restore hearing. Contemporary
      cochlear implant devices consist of up to 22 electrodes. An open question for
      future cochlear implants is whether new electrode designs that enable less
      current spread may provide improved hearing performance through more precise
      control of neural activation, more electrodes, or more precise positioning. Here
      we use a recently proposed information theoretic model for the electro-neural
      interface that enables estimates to be made of the optimal number of electrodes
      for different amounts of current spread. We apply information theoretic
      approaches for finding the channel capacity in the model to enable estimates of
      optimal electrode usage probabilities and positions. We also compare the
      performance in the model when auditory nerve fibers are assumed to be
      heterogenous, with a random distribution of firing thresholds and relative
      spreads, versus an assumption that they are all identical. 

PMID- 24111101
TI  - Optimal stimulus profiles for neuroprosthetic devices: monophasic versus biphasic
      stimulation.
AB  - Designing stimulation signals for neuroprosthetic devices can be cast as an
      optimal control problem. Rectangular Lilly-type stimulation waveforms have been
      used extensively in these devices. In this paper, we rigorously formulate the
      charge optimization problem from a control perspective and distinguish between
      monophasic and biphasic stimuli. We show that for a monophasic stimulus, the
      important factor in stimulating a neuron is the total delivered charge per unit
      cell membrane. This factor is a consequence of the subthreshold linear behavior
      of the neural membrane. On the other hand, biphasic pulses, which are ubiquitous
      in the neuron stimulation context, can stimulate a neuron in its non-linear
      range, thereby challenging the finding that total charge delivery is the only
      critical factor. As a result, there may be even more optimal stimulus profiles
      than Lilly-type rectangular waveforms for biphasic stimulation. Furthermore,
      solving the charge minimization problem also will reduce the risk of electrode
      corrosion, which is an important factor in improving the performance of
      neuroprosthetic devices. 

PMID- 24111102
TI  - On the objective assessment of the auditory brainstem response measurement
      quality.
AB  - Auditory Brainstem Responses (ABRs) are commonly used in clinical practice to
      determine hearing impairments and hearing thresholds. Although many research
      groups work on automatic recognition of ABRs - in order to decrease the
      acquisition times - measures to determine the quality of ABR measurements
      objectively are still missing. In fact, recently released new standards for
      electroencephalographic measurements in auditory examinations require an
      objective measurement quality assessment for neurodiagnostic devices. Thus there
      is a pressing need for the development and evaluation of such a quality control.
      In this study, we propose (a) a novel technique for the assessment of the ABR
      measurement quality and (b) evaluate and compare this technique to two other
      approaches which have been suggested in literature as required by the new
      standards. 

PMID- 24111103
TI  - Multi-domain feature analysis for depression: a study of N170 in time, frequency
      and spatial domains simultaneously.
AB  - This study investigated the differences in event-related potentials (ERPs)
      between depression and normal control groups by using the cue-target paradigm
      with facial expressions as stimuli. Conventional ERPs analysis did not show a
      significant difference in the N170 amplitude or latency between the two groups.
      However, the multi-domain feature analysis of N170 by nonnegative tensor
      factorization (NTF) indicated that N170 in depression group had lower power
      compared with the normal control group for all three different emotional (i.e.,
      happy, neutral, and sad) facial stimuli (Q <= 0.05). The results revealed the
      perceptual early-stage dysfunction in face processing for depression.

PMID- 24111104
TI  - Characterization of the spontaneous electroencephalographic activity in
      Alzheimer's disease using disequilibria and graph theory.
AB  - The aim of this research was to study the changes that Alzheimer's disease (AD)
      elicits in the organization of brain networks. For this task, the
      electroencephalographic (EEG) activity from 32 AD patients and 25 healthy
      controls was analyzed. In a first step, a disequilibrium measure, the Euclidean
      distance (ED), was used to estimate the similarity between the spectral content
      of each pair of electrodes. In a second step, the similarity matrices were used
      to generate the corresponding graphs, from which two parameters were computed to
      characterize the network structure: the mean clustering coefficient and the mean
      path length. Results revealed significant changes (p<0.05) in ED values, as well
      as in the mean clustering coefficient and the mean path length, though they
      depend on the specific frequency band. Our findings suggest that AD is
      accompanied by a significant frequency-dependent alteration of brain network
      organization. 

PMID- 24111105
TI  - A cepstral analysis based method for quantifying the depth of anesthesia from
      human EEG.
AB  - In this paper, a cepstral analysis based approach to measuring the depth of
      anesthesia (DoA) is presented. Cepstral analysis is a signal processing technique
      widely used especially for speech recognition in order to extract speech
      information regardless of vocal cord characteristics. The resulting index for the
      DoA is called index based on cepstral analysis (ICep). The Fisher criterion is
      engaged to evaluate the performance of indices. All analyses are based on a
      single-channel electroencephalogram (EEG) of 10 human subjects. To validate the
      proposed technique, ICep is compared with bispectral index (BIS), which is the
      most commonly used method to estimate the level of consciousness via EEG during
      general anesthesia. The results show that ICep has high correlation with BIS, and
      is outstanding in terms of the Fisher criterion and offers faster tracking than
      BIS in the transition from consciousness to unconsciousness. 

PMID- 24111106
TI  - A study of morphology-based wavelet features and multiple-wavelet strategy for
      EEG signal classification: results and selected statistical analysis.
AB  - Automatic detection and classification of Epileptiform transients is an open and
      important clinical issue. In this paper, we test 5 feature sets derived from a
      group of morphology-based wavelet features and compare the results with that of a
      Guler-suggested feature set. We also implement a multiple-mother-wavelet strategy
      and compare performance with the usual single-mother-wavelet strategy. The
      results indicate that both the derived features and the multiple-mother-wavelet
      strategy improved classifier performance, using a variety of performance
      measures. We assess the statistical significance of the performance improvement
      of the new feature sets/strategy. In most cases, the performance improvement is
      either significant or highly significant. 

PMID- 24111107
TI  - Diagnosis method of mild cognitive impairment based on power variance of EEG.
AB  - Mild cognitive impairment (MCI) patients and healthy people were classified by
      using a "power variance function (PVF)", namely, an index of
      electroencephalography (EEG) proposed in a previous report. PVF is defined by
      calculating variance of the power variability of an EEG signal at each frequency
      of the signal using wavelet transform. After confirming that the distribution of
      PVFs of the subjects was a normal distribution at each frequency, the
      distributions of PVFs of 25 MCI patients and those of 57 healthy people were
      compared in terms of Z-score. The comparison results indicate that for the MCI
      patients, the PVFs in the theta band are significantly higher in left parieto
      occipital area and that those in the beta band are lower in the bitemporal area.
      Multidimensional discriminant analysis using the PVF in the theta-beta band
      recorded only on four electrodes on the left parieto-occipital area could be used
      to classify MCI patients from healthy people with leave-one-out accuracy of
      87.5%. This indicates the possibility of diagnosing MCI by using EEG signals
      recorded only on a few electrodes. 

PMID- 24111109
TI  - Independent Component Analysis of EEG-fMRI data for studying epilepsy and
      epileptic seizures.
AB  - Here we present a method for classifying fMRI independent components (ICs) by
      using an optimized algorithm for the individuation of noisy signals from sources
      of interest. The method was applied to estimate brain activations from combined
      EEG-fMRI data for the exploration of epilepsy. Spatial ICA was performed using
      the above-mentioned optimized algorithm and other three popular algorithms. ICs
      were sorted considering the value: of the coefficients of determination R2,
      obtained from the multiple regression analysis with morphometric maps of cerebral
      matter; of the kurtosis, which features the signal energy. The validation of the
      method was performed comparing the brain activations obtained with those resulted
      using the General Linear Model (GLM). The ICA-derived activations in different
      datasets comprised subareas of the GLM-revealed activations, even if the volume
      and the shape of activated areas do not correspond exactly. The method proposed
      also detects additional negative regions implicated in a default mode of brain
      activity, and not clearly identified by GLM. Compared with a traditional GLM
      approach, the ICA one provides a flexible way to analyze fMRI data that reduces
      the assumptions placed upon the hemodynamic response of the brain and the
      temporal constrains. 

PMID- 24111110
TI  - Exploiting intracardiac and surface recording modalities for atrial signal
      extraction in atrial fibrillation.
AB  - During atrial fibrillation (AF), atrial activity (AA) on the surface ECG consists
      of a pattern of quasi-periodic oscillations (f-waves), which are related to the
      electrical activation of the atrial substrate. However, to date no direct
      comparison between the extracted f-wave pattern in surface recordings and
      specific activation sites within the atria has been carried out. In the present
      study, one reference intracardiac modality consisting of a bipolar electrogram
      (EGM) recorded from the left atrial appendage (LAA) is exploited for the first
      time to guide the extraction of LAA electrical activity from standard 12-lead ECG
      recordings. A periodic component analysis (piCA) technique is employed for this
      task. The performance of the proposed multimodal extraction technique is compared
      to that obtained employing a noninvasive, fully blind approach, namely,
      independent component analysis (ICA). On a database of 31 AF patients, results
      suggest that the estimation of LAA activity is indeed possible, even though its
      contribution to the ECG total power is relatively low. Interestingly, ICA seems
      to provide a slightly better estimation of LAA activation rate, expressed in
      terms of dominant frequency (DF). On the other hand, the multimodal invasive
      approach performs better QRST complex suppression and provides AA waveforms with
      narrower spectra. 

PMID- 24111111
TI  - Comparison of correlation analysis and JointICA for simultaneous EEG-fMRI
      recordings on contour integration task.
AB  - Multimodal approaches to brain imaging are getting increasingly popular among the
      neuroscience comunity. One such multimodal approach is the combination of
      electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). In
      this paper we demonstrate two EEG-fMRI integration methods for contour
      integration task. First, we derrive the contour-selectivity measures from event
      related potential (ERP) and fMRI data, and explore the correlation between the
      two. In this way, we connect the spatial information from fMRI with the temporal
      information from ERPs. Thereafter, the results from this approach are compare to
      JointICA integration approach [5], [6], which aims at extracting spatio-temporal
      independent components, which are the combination of ERP and fMRI activations. 

PMID- 24111112
TI  - Structure-revealing data fusion model with applications in metabolomics.
AB  - In many disciplines, data from multiple sources are acquired and jointly analyzed
      for enhanced knowledge discovery. For instance, in metabolomics, different
      analytical techniques are used to measure biological fluids in order to identify
      the chemicals related to certain diseases. It is widely-known that, some of these
      analytical methods, e.g., LC-MS (Liquid Chromatography - Mass Spectrometry) and
      NMR (Nuclear Magnetic Resonance) spectroscopy, provide complementary data sets
      and their joint analysis may enable us to capture a larger proportion of the
      complete metabolome belonging to a specific biological system. Fusing data from
      multiple sources has proved useful in many fields including bioinformatics,
      signal processing and social network analysis. However, identification of common
      (shared) and individual (unshared) structures across multiple data sets remains a
      major challenge in data fusion studies. With a goal of addressing this challenge,
      we propose a novel unsupervised data fusion model. Our contributions are two
      fold: (i) We formulate a data fusion model based on joint factorization of
      matrices and higher-order tensors, which can automatically reveal common and
      individual components. (ii) We demonstrate that the proposed approach provides
      promising results in joint analysis of metabolomics data sets consisting of
      fluorescence and NMR measurements of plasma samples in terms of separation of
      colorectal cancer patients from controls. 

PMID- 24111113
TI  - The quest for single trial correlations in multimodal EEG-fMRI data.
AB  - In the past decade, technological advances have made it possible to reliably
      measure brain activity using simultaneous EEG-fMRI recordings inside an MR
      scanner. The main challenge then became to investigate the coupling between the
      EEG and fMRI signals in order to benefit from the simultaneously integrated
      temporal and spatial resolution. Although it is crucial to know when features in
      EEG and fMRI are expected to correlate with each other before the identification
      of common sources from multimodal data is possible, it is still a matter of
      debate. In this study, we address this question by analysing EEG and fMRI data
      separately from a face processing task. We show that we are able to reliably
      estimate single trial (ST) dynamics of face processing in EEG and fMRI data
      separately in four subjects. However, no correlation is found between the
      modalities. This implies that in this task modality-specific information is
      larger than the information that is shared by the modalities. 

PMID- 24111114
TI  - Detection of cigarette smoke inhalations from respiratory signals using reduced
      feature set.
AB  - A combination of wearable Respiratory Inductive Plethysmograph and a hand-to
      mouth Proximity Sensor (PS) can be used to monitor smoking habits and smoke
      exposure in cigarette smokers. In our previous work, detection of smoke
      inhalations was achieved by using a Support Vector Machine (SVM) classifier
      applied to raw sensor signals with 1503-element feature vectors. This study uses
      empirically-defined 27 features computed from the sensor signals to reduce the
      length of vectors. Further reduction in the length of the feature vectors was
      achieved by a forward feature selection algorithm, identifying from 2 to 16
      features most critical for smoke inhalations detection. For individual detection
      models, the 1503-element feature vectors, 27-element feature vectors and reduced
      feature vectors resulted in F-scores of 90.1%, 68.7% and 94% respectively. For
      the group models, F-scores were 81.3%, 65% and 67% respectively. These results
      demonstrate feasibility of detecting smoke inhalations with a computed feature
      set, but suggest high individuality of breathing patterns associated with
      smoking. 

PMID- 24111115
TI  - Improving transient state myoelectric signal recognition in hand movement
      classification using gyroscopes.
AB  - Pattern recognition of myoelectric signals in upper-limb prosthesis control has
      been subject to intense research for several years. However, few systems have yet
      been successfully clinically implemented. One possible explanation for this
      discrepancy is that published reports mostly focus on classification accuracy of
      myoelectric signals recorded under laboratory conditions as the metric for the
      system's performance. These data are usually acquired only during the static
      state of the contraction in a fixed seated position. This supports the test
      subject in performing repeatable contractions throughout the experiment and
      generally results in an unrealistically high classification accuracy. In clinical
      testing however, subjects have to perform various activities of daily living,
      causing the limb to move in different positions. These variations in limb
      positions can significantly decrease robustness and usability of myoelectric
      control systems. Recent reports have shown that the so-called limb position
      effect can be resolved for the static state of the signal by adding accelerometer
      data to the feature vector. Including data from the transient state of the
      signals for classifier training generally significantly increases the
      classification error so it is mostly not considered in published reports. In this
      paper, we investigate the classification accuracy of transient EMG data, taking
      into account the limb position effect. We demonstrate that a classifier trained
      with features from EMG, accelerometer and gyroscope outperforms classifiers using
      only EMG or EMG and accelerometer data when classifying transient EMG data. 

PMID- 24111116
TI  - Boosting specificity of MEG artifact removal by weighted support vector machine.
AB  - An automatic artifact removal method of magnetoencephalogram (MEG) was presented
      in this paper. The method proposed is based on independent components analysis
      (ICA) and support vector machine (SVM). However, different from the previous
      studies, in this paper we consider two factors which would influence the
      performance. First, the imbalance factor of independent components (ICs) of MEG
      is handled by weighted SVM. Second, instead of simply setting a fixed weight to
      each class, a re-weighting scheme is used for the preservation of useful MEG ICs.
      Experimental results on manually marked MEG dataset showed that the method
      proposed could correctly distinguish the artifacts from the MEG ICs. Meanwhile,
      99.72% +/- 0.67 of MEG ICs were preserved. The classification accuracy was 97.91%
      +/- 1.39. In addition, it was found that this method was not sensitive to
      individual differences. The cross validation (leave-one-subject-out) results
      showed an averaged accuracy of 97.41% +/- 2.14.

PMID- 24111117
TI  - Online LS-SVM based multi-step prediction of physiological tremor for surgical
      robotics.
AB  - Performance of robotics based hand-held surgical devices in real-time is mainly
      dependent on accurate filtering of physiological tremor. The presence of phase
      delay in sensors (hardware) and filtering (software) processes affects the
      cancellation accuracy. This paper focuses on developing an estimation algorithm
      to improve the estimation accuracy in the presence of phase delay for real-time
      implementations. Moving window based online training approach for least squares
      support vector machines (LSSVM) is employed in this paper for tremor estimation.
      A study is conducted with tremor data recorded from the subjects to analyze the
      suitability of proposed approach for both single-step and multi-step prediction. 

PMID- 24111118
TI  - Classification of schizophrenia using Genetic Algorithm-Support Vector Machine
      (GA-SVM).
AB  - Recently, Event-Related Potential (ERP) has being the most popular method in
      evaluating brain waves of schizophrenia patients. ERP is one of the
      electroencephalography (EEG), which is measured the change of brain waves after
      giving patients certain stimulations instead of resting state. However, with
      traditional statistical analysis method, both P50 and MMN showed significant
      difference between controls and patients but not in Gamma band. Gamma band is a
      30-50 Hz auditory stimulation which had been suggested may be abnormal in
      schizophrenia patients. Our data are recruited from 5 schizophrenia patients and
      5 controls in National Taiwan University Hospital have been tested with this
      platform. The results showed that detection rate is 88.24% and we also analyzed
      the importance of features, including Standard Deviation (SD) and Total Variation
      (TotalVar) in different stage of wavelet transform. Therefore, this proposed
      methodology could serve as a valuable clinical decision support for physiologists
      in evaluating schizophrenia. 

PMID- 24111119
TI  - Selection of cortical neurons for identifying movement transitions in stand and
      squat.
AB  - Neural signals collected from motor cortex were quantified for identification of
      subject's specific movement intentions in a Brain Machine Interface (BMI). Neuron
      selection serves as an important procedure in this decoding process. In this
      study, we proposed a neuron selection method for identifying movement transitions
      in standing and squatting tasks by analyzing cortical neuron spike train
      patterns. A nonparametric analysis of variation, Kruskal-Wallis test, was
      introduced to evaluate whether the average discharging rate of each neuron
      changed significantly among different motion stages, and thereby categorize the
      neurons according to their active periods. Selection was performed based on
      neuron categorizing information. Finally, the average firing rates of selected
      neurons were assembled as feature vectors and a classifier based on support
      vector machines (SVM) was employed to discriminate different movement stages and
      identify transitions. The results indicate that our neuron selection method is
      accurate and efficient for finding neurons correlated with movement transitions
      in standing and squatting tasks. 

PMID- 24111121
TI  - Segmentation of aortic flow in real time magnetic resonance images.
AB  - Real-time spiral phase contrast magnetic resonance imaging (MRI) is capable of
      non-invasively measuring the stroke volume associated with each individual
      heartbeat. The quality of these measurements depends on how good the segmentation
      of the interface between aortic wall and lumen is. Such process is hampered by
      the low-resolution and low-contrast nature of real-time images. Image
      segmentation using traditional techniques has proven not robust. This paper
      presents a novel model-based approach, which is capable of very accurately
      segmenting aortic flow. Instead of attempting to achieve a millimetrically
      accurate segmentation of the wall-lumen interface, the proposed algorithm focuses
      on separating the aortic flow from neighboring flows. This provides robustness,
      even when this interface is not visually distinguishable. The proposed
      segmentation takes real-time MRI one step further towards becoming the non
      invasive gold standard for assessment of stroke volume variability. 

PMID- 24111122
TI  - Direct measurement of speed of sound in cartilage in situ using ultrasound and
      magnetic resonance images.
AB  - This study verified the accuracy of the speed of sound (SOS) measured by the
      combination method, which calculates the ratio between the thickness values of
      cartilage measured by using the magnetic resonance imaging (MRI) and the
      ultrasonic pulse-echo imaging, and investigated in vivo application of this
      method. SOS specific to an ultrasound imaging device was used as a reference
      value to calculate the actual SOS from the ratio of cartilage thicknesses
      obtained from MR and ultrasound images. The accuracy of the thickness measurement
      was verified by comparing results obtained using MRI and a non-contact laser, and
      the accuracy of the calculated SOS was confirmed by comparing results of the
      pulse-echo and transmission methods in vitro. The difference between laser and
      MRI measurements was 0.05 +/- 0.22 mm. SOS values in a human knee measured by the
      combination method in the medial and lateral femoral condyles were 1650 +/- 79
      and 1642 +/- 78 m/s, respectively (p < 0.05). The results revealed the
      feasibility of in situ SOS measurement using the combination method. 

PMID- 24111123
TI  - Ultrasound lesion segmentation using clinical knowledge-driven constrained level
      set.
AB  - Ultrasound lesion segmentation is an important and challenging task. Comparing
      with other methods, region-based level set has many advantages, but still
      requires considerable improvement to deal with the characteristic of lesions in
      the ultrasound modality such as shadowing, speckle and heterogeneity. In the
      clinical workflow, the physician would usually denote long and short axes of a
      lesion for measurement purpose yielding four markers in an image. Inspired by
      this workflow, a constrained level set method is proposed to fully utilize these
      four markers as prior knowledge and global constraint for the segmentation.
      First, the markers are detected using template-matching algorithm and B-Spline is
      applied to fit four markers as the initial contour. Then four-marker constrained
      energy is added to the region-based local level set to make sure that the contour
      evolves without deviation from the four markers. Finally the algorithm is
      implemented in a multi-resolution scheme to achieve sufficient computational
      efficiency. The performance of the proposed segmentation algorithm was evaluated
      by comparing our results with manually segmented boundaries on 308 ultrasound
      images with breast lesions. The proposed method achieves Dice similarity
      coefficient 89.49 +/- 4.76% and could be run in real-time.

PMID- 24111124
TI  - Prior knowledge enhanced random walk for lung tumor segmentation from low
      contrast CT images.
AB  - The separation of a lung tumor from adjacent normal tissue, which has similar
      intensity values and indistinct boundaries on low-contrast CT images is a
      challenging task. In this paper, a prior knowledge enhanced random walk (RW) is
      proposed to account for the prior functional knowledge from PET and intensity
      information from CT. The prior knowledge acquired from PET is used for the
      automated selection of foreground seeds, defined as the tumor confidence region,
      the background seeds and the walking range to increase computational efficiency
      of the RW algorithm in CT. The tumor confidence region is also used for balancing
      transition, and thus limiting the information propagation range through a weight
      factor. The experimental evaluation on 18 low-contrast CT images with manual
      tumor segmentation demonstrated that our method outperformed RW and random walk
      from restart (RWR) as measured by the Dice similarity coefficient (DSC). 

PMID- 24111125
TI  - Segmentation using Sparse Shape Composition and minimally supervised method in
      liver surgery planning system.
AB  - Liver surgery planning system plays an important role in achieving the optimized
      surgery plan in Living Donor Liver Transplantation (LDLT). Segmentation of liver
      is a very challenging component in liver surgery planning systems. Patient
      specific shape prior is of great significance in improving the robustness of
      liver segmentation. However, complex liver shape variations among different
      patients are difficult to model, which affects the accurate segmentation in liver
      surgery planning. To address this problem, we incorporated the Sparse Shape
      Composition (SSC) in the computer assisted liver surgery planning system. The
      basic modules of the system consist of: (1) Segmentation module. The Sparse Shape
      Composition (SSC) model is employed to get a patient-specific liver shape prior
      and then the shape prior is combined with a minimally supervised method to
      segment the liver parenchyma, hepatic vessels and tumors simultaneously. (2)
      Approximation of liver segments. It divides the liver into several functionally
      independent segments. (3) Visualization module. The result of clinical experiment
      shows this system has a good performance in providing accurate and robust liver
      surgery planning. 

PMID- 24111126
TI  - Lung image patch classification with automatic feature learning.
AB  - Image patch classification is an important task in many different medical imaging
      applications. The classification performance is usually highly dependent on the
      effectiveness of image feature vectors. While many feature descriptors have been
      proposed over the past years, they can be quite complicated and domain-specific.
      Automatic feature learning from image data has thus emerged as a different trend
      recently, to capture the intrinsic image features without manual feature design.
      In this paper, we propose to create multi-scale feature extractors based on an
      unsupervised learning algorithm; and obtain the image feature vectors by
      convolving the feature extractors with the image patches. The auto-generated
      image features are data-adaptive and highly descriptive. A simple classification
      scheme is then used to classify the image patches. The proposed method is generic
      in nature and can be applied to different imaging domains. For evaluation, we
      perform image patch classification to differentiate various lung tissue patterns
      commonly seen in interstitial lung disease (ILD), and demonstrate promising
      results. 

PMID- 24111127
TI  - The use of pseudo-landmarks for craniofacial analysis: a comparative study with
      L1-regularized logistic regression.
AB  - Morphometrics, the quantitative analysis of shape, is used by craniofacial
      researchers to study abnormalities in human face shapes. Most of the work in
      craniofacial morphometrics uses landmark points that are manually marked on 3D
      face data and processed via a generalized Procrustes analysis. For large data
      sets this manual process is very time-consuming. Dense sets of pseudo-landmarks
      have also been proposed and successfully used for classification and clustering,
      but the two main methods in the literature are very computationally intensive. We
      have developed a computationally simple method that can compute pseudo-landmark
      points at different resolutions from 3D meshes of human faces. In this paper, we
      perform a comparative study employing L1-regularized logistic regression to train
      a classifier that predicts the sex of 500 normal adult face meshes in order to
      compare our method to two alternative pseudo-landmark methods and a distance
      matrix approach.Our results show that our method, which is fully automatic,
      achieved similar results to the best-scoring methods with no manual landmarking
      and with much lower computation time. Use of the distance matrix did not improve
      classification results. 

PMID- 24111128
TI  - Cell nuclei segmentation in fluorescence microscopy images using inter- and intra
      region discriminative information.
AB  - Automated segmentation of cell nuclei in microscopic images is critical to high
      throughput analysis of the ever increasing amount of data. Although cell nuclei
      are generally visually distinguishable for human, automated segmentation faces
      challenges when there is significant intensity inhomogeneity among cell nuclei or
      in the background. In this paper, we propose an effective method for automated
      cell nucleus segmentation using a three-step approach. It first obtains an
      initial segmentation by extracting salient regions in the image, then reduces
      false positives using inter-region feature discrimination, and finally refines
      the boundary of the cell nuclei using intra-region contrast information. This
      method has been evaluated on two publicly available datasets of fluorescence
      microscopic images with 4009 cells, and has achieved superior performance
      compared to popular state of the art methods using established metrics. 

PMID- 24111129
TI  - Multi-channels statistical and morphological features based mitosis detection in
      breast cancer histopathology.
AB  - Accurate counting of mitosis in breast cancer histopathology plays a critical
      role in the grading process. Manual counting of mitosis is tedious and subject to
      considerable inter- and intra-reader variations. This work aims at improving the
      accuracy of mitosis detection by selecting the color channels that better capture
      the statistical and morphological features having mitosis discrimination from
      other objects. The proposed framework includes comprehensive analysis of first
      and second order statistical features together with morphological features in
      selected color channels and a study on balancing the skewed dataset using SMOTE
      method for increasing the predictive accuracy of mitosis classification. The
      proposed framework has been evaluated on MITOS data set during an ICPR 2012
      contest and ranked second from 17 finalists. The proposed framework achieved 74%
      detection rate, 70% precision and 72% F-Measure. In future work, we plan to apply
      our mitosis detection tool to images produced by different types of slide
      scanners, including multi-spectral and multi-focal microscopy. 

PMID- 24111130
TI  - Discretized data pattern in endoscopic gastritis images using Dynamic Window and
      Pairwise Gini Criterion.
AB  - Curent standard clinical procedure for gastritis is via endoscopy by performing
      an invasive procedure. The procedure takes tissue samples from patient's antrum
      and diagnoses based on pathological evaluation. Several non-invasive computer
      aided visualization studies have been conducted to perform feature extraction
      from the endoscopic gastritis images. Based on an extensive literature search,
      studies to extract data patterns from the images has never been conducted.
      Discretization or data pattern extraction is one of the data pre-processing
      technique that promotes classification. However, data pre-processing is often
      overlooked by many researchers because it takes up time from the overall
      classification process. Thus, data pre-processing studies offer faster pre
      processing time and compromise with the error rate. Trade-off has been a
      prolonged issue in discretization studies. Often discretization time is reduced,
      and the error rate is compromised. However, the proposed discretization algorithm
      implemented on extracted features from gastritis images has reduced not only the
      discretization time but also the error rate. As a result of discretization
      process, it generates good generalization of the data patterns to the endoscopic
      gastritis extracted features. Thus, determining discretized data patterns from
      the extracted endoscopic gastritis images may improve the overall classification
      process in terms of accuracy and learning time. 

PMID- 24111131
TI  - Automatic dental arch detection and panoramic image synthesis from CT images.
AB  - Due to accurate 3D information, computed tomography (CT), especially cone-beam CT
      or dental CT, has been widely used for diagnosis and treatment planning in
      dentistry. Axial images acquired from both medical and dental CT scanners can
      generate synthetic panoramic images similar to typical 2D panoramic radiographs.
      However, the conventional way to reconstruct the simulated panoramic images is to
      manually draw the dental arch on axial images. In this paper, we propose a new
      fast algorithm for automatic detection of the dental arch. Once the dental arch
      is computed, a series of synthetic panoramic images as well as a ray-sum
      panoramic image can be automatically generated. We have tested the proposed
      algorithm on 120 CT axial images and all of them can provide the decent estimate
      of the dental arch. The results show that our proposed algorithm can mostly
      detect the correct dental arch. 

PMID- 24111132
TI  - Wearable cuff-less PTT-based system for overnight blood pressure monitoring.
AB  - A wearable cuff-less pulse transit time (PTT) based monitoring device is
      developed for ambulatory blood pressure (BP) monitoring. Ten healthy subjects
      (aged 27 +/- 4 years old) underwent 24-hour ambulatory BP monitoring using 1) a
      standard brachial cuff-based oscillometric device as reference and 2) the
      proposed cuff-less PTT measuring system. Raw PTT and BP measurements were
      linearly interpolated and then smoothed by a low-pass filter to remove aliasing
      effect caused by the low sampling rate and synchronized. Resampled PTT and BP
      were assessed for correlation using correlation coefficients and Bland-Altman
      plots. Our study showed that PTT estimated systolic BP most accurately within 4.8
      +/- 4.3 mmHg on healthy young subjects during sleep time. We conclude from this
      study that the proposed cuff-less PTT-based BP monitoring system has potential to
      be a less intrusive alternative to standard oscillometric method for long-term
      overnight BP monitoring.

PMID- 24111133
TI  - Blood pressure estimation from pulse wave velocity measured on the chest.
AB  - Recently, monitoring of blood pressure fluctuation in the daily life is focused
      on in the hypertension care area to predict the risk of cardiovascular and
      cerebrovascular disease events. In this paper, in order to propose an alternative
      system to the existed ambulatory blood pressure monitoring (ABPM)
      sphygmomanometer, we have developed a prototype of small wearable device
      consisting of electrocardiogram (ECG) and photopelthysmograph (PPG) sensors. In
      addition, it was examined whether blood pressure can be estimated based on pulse
      wave transit time (PWTT) only by attaching that device on the surface of the
      chest. We indicated that our system could also sense tendency of time-dependent
      change of blood pressure by measuring pulse of vessel over the sternum while its
      propagation distance is short. 

PMID- 24111134
TI  - An inertial sensor-based system to develop motor capacity in children with
      cerebral palsy.
AB  - Learning to communicate with alternative augmentative communication devices can
      be difficult because of the difficulty of achieving controlled interaction while
      simultaneously learning to communicate. What is needed is a device that harnesses
      a child's natural motor capabilities and provides the means to reinforce them. We
      present a kinematic sensor-based system that learns a child's natural gestural
      capability and allows him/her to practice those capabilities in the context of a
      game. Movement is captured with a single kinematic sensor that can be worn
      anywhere on the body. A gesture recognition algorithm interactively learns
      gesture models using kinematic data with the help of a nearby teacher. Learned
      gesture models are applied in the context of a game to help the child practice
      gestures to gain better consistency. The system was successfully tested with a
      child over two sessions. The system learned four candidate gestures: lift hand,
      sweep right, twist right and punch forward. These were then used in a game. The
      child showed better consistency in performing the gestures as each session
      progressed. We aim to expand on this work by developing qualitative scores of
      movement quality and quantifying algorithm accuracy on a larger population over
      long periods of time. 

PMID- 24111135
TI  - Wireless patch sensor for remote monitoring of heart rate, respiration, activity,
      and falls.
AB  - Unobtrusive continuous monitoring of important vital signs and activity metrics
      has the potential to provide remote health monitoring, at-home screening, and
      rapid notification of critical events such as heart attacks, falls, or
      respiratory distress. This paper contains validation results of a wireless
      Bluetooth Low Energy (BLE) patch sensor consisting of two electrocardiography
      (ECG) electrodes, a microcontroller, a tri-axial accelerometer, and a BLE
      transceiver. The sensor measures heart rate, heart rate variability (HRV),
      respiratory rate, posture, steps, and falls and was evaluated on a total of 25
      adult participants who performed breathing exercises, activities of daily living
      (ADLs), various stretches, stationary cycling, walking/running, and simulated
      falls. Compared to reference devices, the heart rate measurement had a mean
      absolute error (MAE) of less than 2 bpm, time-domain HRV measurements had an RMS
      error of less than 15 ms, respiratory rate had an MAE of 1.1 breaths per minute
      during metronome breathing, posture detection had an accuracy of over 95% in two
      of the three patch locations, steps were counted with an absolute error of less
      than 5%, and falls were detected with a sensitivity of 95.2% and specificity of
      100%.

PMID- 24111136
TI  - Analysis of subtle movements related to neurodegenerative diseases using wearable
      inertial sensors: a study in healthy subjects.
AB  - Evaluation of movement disorders is a useful tool for the diagnostic and
      monitoring of diseases related with damage of the motor control systems, such as
      Parkinson's disease. The evaluation of well characterized movement disorders has
      been proposed using different techniques each one with their advantages and
      limitations. This document propose the use a system based on inertial sensors and
      wireless technology for the measurement and evaluation of three of the most
      common movement disorders related with Parkinson's disease. Measurement of
      Anticipatory Postural Adjustments (APAs), Postural Sway and hand's tremor were
      carried out using inertial sensors modules (IMU). Results obtained from
      measurements in elderly and young subjects are presented, as well as the set up
      and parameters suggested for quantitative analysis. 

PMID- 24111137
TI  - Stress classification by separation of respiratory modulations in heart rate
      variability using orthogonal subspace projection.
AB  - The influence of respiration on the heart rate is a phenomenon known as
      respiratory sinus arrhythmia. However, effects of respiration are often ignored
      in studies of heart rate variability. In this paper, we take respiratory
      influences into account by separating the tachogram in two components, one
      related to respiration and one residual component, using orthogonal subspace
      projection. We demonstrate that it is important to remove respiratory influences
      during classification of rest and mental stress. Using merely the original
      tachogram, the classification accuracy is 57.13%, while the use of the residual
      tachogram results in an almost perfect classification (accuracy = 97.88%). 

PMID- 24111138
TI  - Complexity of the heart rhythm after heart transplantation by entropy of
      transition network for RR-increments of RR time intervals between heartbeats.
AB  - Network models have been used to capture, represent and analyse characteristics
      of living organisms and general properties of complex systems. The use of network
      representations in the characterization of time series complexity is a relatively
      new but quickly developing branch of time series analysis. In particular, beat-to
      beat heart rate variability can be mapped out in a network of RR-increments,
      which is a directed and weighted graph with vertices representing RR-increments
      and the edges of which correspond to subsequent increments. We evaluate entropy
      measures selected from these network representations in records of healthy
      subjects and heart transplant patients, and provide an interpretation of the
      results. 

PMID- 24111139
TI  - Instantaneous nonlinear assessment of complex cardiovascular dynamics by Laguerre
      Volterra point process models.
AB  - We report an exemplary study of instantaneous assessment of cardiovascular
      dynamics performed using point-process nonlinear models based on Laguerre
      expansion of the linear and nonlinear Wiener-Volterra kernels. As quantifiers,
      instantaneous measures such as high order spectral features and Lyapunov
      exponents can be estimated from a quadratic and cubic autoregressive formulation
      of the model first order moment, respectively. Here, these measures are evaluated
      on heartbeat series coming from 16 healthy subjects and 14 patients with
      Congestive Hearth Failure (CHF). Data were gathered from the on-line repository
      PhysioBank, which has been taken as landmark for testing nonlinear indices.
      Results show that the proposed nonlinear Laguerre-Volterra point-process methods
      are able to track the nonlinear and complex cardiovascular dynamics,
      distinguishing significantly between CHF and healthy heartbeat series. 

PMID- 24111140
TI  - Multi-scale Tone Entropy in differentiating physiologic and synthetic RR time
      series.
AB  - Heart rhythm is extrinsically modulated by the autonomic nervous system and
      recently, the Tone-Entropy (TE) measurement was reported as a measure of
      autonomic balance and activity in time domain HRV analysis. Current algorithm for
      T-E measurement describes only beat-to-beat or influence of a heart beat on a
      train of succeeding beats on a single scale. Therefore, conventional T-E analysis
      has often not been able to discern various physiological conditions using heart
      rate variability (HRV) signal. In this study, we will present a mathematical
      framework to define multi-scale T-E analysis, apply this in differentiating
      physiological and synthetic RR time series. Finally, we compare the performance
      of proposed parameters with conventional T-E measurements. 

PMID- 24111141
TI  - Evaluating cardiovascular risk using the tone-entropy algorithm.
AB  - Currently the Framingham equation is the most often used cardiovascular risk
      calculator in health care. The equation requires data for age, gender,
      cholesterol status, blood pressure, diabetes status and smoking. A large
      proportion of the morbidity and mortality associated with cardiovascular disease
      is due to arrhythmic events that are multifactorial including dysregulation by
      the autonomic nervous system. In this study we applied the tone-entropy algorithm
      for analysis of heart rate variability obtained from 20 minute ECG recordings and
      compared the outcome with the Framingham risk stratification. Our results
      indicate a good agreement between the T-E algorithm and the Framingham risk
      equation suggesting that this algorithm may be of use for initial screening of
      cardiovascular risk as it is noninvasive, economical and easy to use in clinical
      practice.

PMID- 24111142
TI  - Arrhythmic dynamics from singularity analysis of electrocardiographic maps.
AB  - From a point view of nonlinear dynamics, the electrical activity of the heart is
      a complex dynamical system, whose dynamics reflects the actual state of health of
      the heart. Nonlinear signal-processing methods are needed in order to accurately
      characterize these signals and improve understanding of cardiac arrhythmias.
      Recent developments on reconstructible signals and multiscale information content
      show that an analysis in terms of singularity exponents provides compact and
      meaningful descriptors of the structure and dynamics of the system. Such approach
      gives a compact representation atrial arrhythmic dynamics, which can sharply
      highlight regime transitions and arrhythmogenic areas. 

PMID- 24111143
TI  - A flexible algorithm framework for closed-loop neuromodulation research systems.
AB  - Modulation of neural activity through electrical stimulation of tissue is an
      effective therapy for neurological diseases such as Parkinson's disease and
      essential tremor. Researchers are exploring improving therapy through adjustment
      of stimulation parameters based upon sensed data. This requires classifiers to
      extract features and estimate patient state. It also requires algorithms to
      appropriately map the state estimation to stimulation parameters. The latter,
      known as the control policy algorithm, is the focus of this work. Because the
      optimal control policy algorithms for the nervous system are not fully
      characterized at this time, we have implemented a generic control policy
      framework to facilitate exploratory research and rapid prototyping of new
      neuromodulation strategies. 

PMID- 24111144
TI  - A method for actively tracking excitability of brain networks using a fully
      implantable monitoring system.
AB  - This paper introduces a new method for estimating the excitability of brain
      networks. The motivation for this research was to develop a system that can track
      pathological changes in excitability, in diseases such as epilepsy. The ability
      to track excitability may provide a method for anticipating seizures and
      intervening therapeutically. Four normally healthy canines were implanted with
      the Medtronic Activia PC+S deep brain stimulation and sensing system. The devices
      were used to probe the circuit of Papez, with electrical stimulation in the
      anterior nucleus of the thalamus to measure evoked potentials in the hippocampus.
      The canines were given three different dosage levels of anti-convulsant
      medication in an attempt to manipulate the excitability of the network. The
      results showed changes in the morphology of the evoked potentials, following a
      circadian profile and reflecting times of drug delivery. 

PMID- 24111146
TI  - Fatigue test of helical nervous electrodes and weak point analysis of helical
      nervous electrodes design.
AB  - Due to the increasing number of both implantation and removal of the helical
      nervous electrodes, the safety and the reliability of the electrode becomes an
      important issue in its clinical application-particularly its fatigue failure
      caused by body movement. Utilizing fatigue testing, we evaluated the weak points
      of the helical electrode. Our data analysis for fatigue cycles recorded by the
      fatigue test equipment showed that the adhesive strength between the silicone and
      suture, and the load of the electrode were essential for the mechanical
      durability of the electrode. The locations of the weak points and improvements
      for helical electrode design were given. The suggestions of decreasing damages to
      the nerves in clinical use will be helpful to the surgeons. 

PMID- 24111147
TI  - Electrical or repetitive transcranial magnetic stimulation of primary motor
      cortex for intractable neuropathic pain.
AB  - OBJECTIVE: To assess the pain-relieving effects of motor cortex electrical
      stimulation (MCS) and the predictive factors retrospectively. METHODS: Thirty
      four patients with intractable neuropathic pain underwent MCS; 19 patients had
      cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test
      electrodes were implanted within the central sulcus and on the precentral gyrus.
      Twelve patients received both MCS and repetitive transcranial magnetic
      stimulation (rTMS) of the primary motor cortex. RESULTS: Pain reduction of >50%
      was observed in 12 of 32 (36%) patients with >12 months follow-ups (2 patients
      were excluded because of short follow-up). In 10 of the 12 patients who received
      test electrodes within the central sulcus and on the precentral gyrus, the
      optimal stimulation was MCS within the central sulcus. In 4 of these (40%)
      patients, positive effects were maintained at follow-ups. The pain reduction of
      rTMS significantly correlated with that of MCS during test stimulation.
      CONCLUSIONS: The test stimulation within the central sulcus was more effective
      than that of the precentral gyrus. In the selected patients, chronic stimulation
      within the central sulcus did not significantly improve long-term results.
      Repeated rTMS seems to be same effective as MCS.

PMID- 24111148
TI  - Insomnia types and sleep microstructure dynamics.
AB  - This work aims to investigate sleep microstructure as expressed by Cyclic
      Alternating Pattern (CAP), and its possible alterations in pathological sleep.
      Three groups, of 10 subjects each, are considered: a) normal sleep, b)
      psychophysiological insomnia, and c) sleep misperception. One night sleep PSG and
      sleep macro- micro structure annotations were available per subject. The
      statistical properties and the dynamics of CAP events are in focus. Multiscale
      and non-linear methods are presented for the analysis of the microstructure event
      time series, applied for each type of CAP events, and their combination. The
      results suggest that a) both types of insomnia present CAP differences from
      normal sleep related to hyperarousal, b) sleep misperception presents more
      extensive differences from normal, potentially reflecting multiple sleep
      mechanisms, c) there are differences between the two types of insomnia as regard
      to the intertwining of events of different subtypes. The analysis constitutes a
      contribution towards new markers for the quantitative characterization of
      insomnia, and its subtypes. 

PMID- 24111150
TI  - Quantitative evaluation for the wakefulness state using complexity-based decision
      threshold value in EEG signals.
AB  - Fully awake state of the subjects tends to be an early drowsy state as a result
      from the prolonged time of electroencephalography (EEG) measurements. Such
      situations can complicate the interpretation of EEG signals and hence, the
      wakefulness of the subject should be considered in the inspection. Thus, in the
      present study, a new index for quantitative evaluation of the wakefulness
      (whether either early drowsy or fully awake) state of subjects by using a
      complexity-based decision threshold value was developed. The proposed index was
      based on approximate entropy (ApEn) to quantify the complexity metric, but with
      new parameter values by using a new systematic approach. This index was evaluated
      using occipital-alpha rhythm during eye closure for 45 healthy adult subjects for
      each one of two groups: fully awake and drowsy groups. Our index could show more
      superiority than other conventional spectral-based indices used for evaluating
      the wakefulness state of subjects including relative delta sub band power
      (R.delta), relative theta sub band power (R.theta), power ratio between theta and
      alpha (Ptheta/alpha), and between theta and beta (Ptheta/beta) over occipital
      lobe. Our index is superior than R.delta, R.theta, Ptheta/alpha and Ptheta/beta
      with 10%, 5.5%, 8.9% and 24.4% respectively.

PMID- 24111149
TI  - Time and time-frequency analysis of near-infrared signals for the assessment of
      ozone autohemotherapy long-term effects in multiple sclerosis.
AB  - Ozone autohemotherapy is an emerging therapeutic technique that is gaining
      increasing importance in treating neurological disorders. A validated and
      standard methodology to assess the effect of such therapy on brain metabolism and
      circulation is however still lacking. We used a near-infrared spectroscopy system
      (NIRS) to monitor the cerebral oxygenation of 9 subjects: 4 remitting-relapsing
      multiple sclerosis (MS) sufferers and 5 controls. Subjects were tested before,
      during, and after ozone autohemotherapy. We monitored the concentration changes
      in the level of oxygenated and deoxygenated haemoglobin, and in the level of the
      Cytochrome-c-oxidase (CYT-c). From the time and time-frequency analysis of the
      NIRS signals we extracted 128 variables, which were used to characterize the
      metabolic brain pattern during the therapy. We showed that by using only 7 NIRS
      variables out of 128 it is possible to characterize the metabolic brain pattern
      of the two groups of subjects. The MS subjects showed a marked increase of the
      CYT-c activity and concentration about 40 minutes after the end of the
      autohemotherapy, possibly revealing a reduction of the chronic oxidative stress
      level typical of MS sufferers. From a technical point of view, this preliminary
      study showed that NIRS could be useful to show the effects of ozone
      autohemotherapy at cerebral level, in a long term monitoring. The clinical result
      of this study is the quantitative measurement of the CYT-c level changes in MS
      induced by ozone autohemotherapy. 

PMID- 24111151
TI  - Neuroelectric brain imaging during a real visit of a fine arts gallery: a
      neuroaesthetic study of XVII century Dutch painters.
AB  - Neuroaesthetic is a scientific discipline founded more than a decade ago and it
      refers to the study of the neural bases of beauty perception in art. The aim of
      this paper is to investigate the neuroelectrical correlates of brain activity of
      the observation of real paintings showed in a national fine arts gallery
      (Scuderie del Quirinale) in Rome, Italy. In fact, the present study was designed
      to examine how motivational factors as indexed by EEG asymmetry over the
      prefrontal cortex (relative activity of the left and right hemispheres) could be
      related to the experience of viewing a series of figurative paintings. The fine
      arts gallery was visited by a group of 25 subjects during an exhibition of the
      XVII century Dutch painters. Results suggested a strict correlation of the
      estimated EEG asymmetry with the verbal pleasantness scores reported by the
      subjects (p<0,05) and an inverse correlation of the perceived pleasantness with
      the observed painting's surface dimensions (p<0,002).

PMID- 24111152
TI  - Induced gamma-band brain responses to direct eye contact in the frontal and
      parietal cortices.
AB  - We used simultaneous recordings of the neuromagnetic (MEG) and electrooculogram
      (EOG) recordings on a pair of directly facing subjects, i.e., the sender and the
      observer of the eye gaze, to measure changes in the spontaneous brain activities
      while the observer perceives changes in eye gaze direction of the sender. The MEG
      signals were analyzed in the time-frequency domain to evaluate event-related
      changes in the spontaneous brain activities induced by the onset of eye
      movements. Significant increase in the gamma-band power was observed in the eye
      contact condition compared to the averting condition in the right superior
      parietal, bilateral posterior superior-temporal, and the frontal areas of the
      observer. Together with the preliminary results from the frequency-domain Granger
      Geweke causality analysis, the current results indicate that the connectivity
      between (a) the bilateral frontal areas, and (b) the right frontal and parietal
      areas might be crucial for the perception of eye gaze of the directly facing
      person. The increase in gamma-band activities in these regions might reflect the
      integration of information processed individually in these regions for eye gaze
      perception.

PMID- 24111153
TI  - Amplitude modulation of alpha-band rhythm caused by mimic collision: MEG study.
AB  - Detection of a collision risk and avoiding the collision are important for
      survival. We have been investigating neural responses when humans anticipate a
      collision or intend to take evasive action by applying collision-simulating
      images in a predictable manner. Collision-simulating images and control images
      were presented in random order to 9 healthy male volunteers. A cue signal was
      also given visually two seconds before each stimulus to enable each participant
      to anticipate the upcoming stimulus. Magnetoencephalograms (MEG) were recorded
      with a 76-ch helmet system. The amplitude of alpha band (8-13 Hz) rhythm when
      anticipating the upcoming collision-simulating image was significantly smaller
      than that when anticipating control images even just after the cue signal. This
      result demonstrates that anticipating a negative (dangerous) event induced event
      related desynchronization (ERD) of alpha band activity, probably caused by
      attention. The results suggest the feasibility of detecting endogenous brain
      activities by monitoring alpha band rhythm and its possible applications to
      engineering systems, such as an automatic collision evasion system for
      automobiles. 

PMID- 24111154
TI  - Subspace electrode selection methodology for EEG multiple source localization
      error reduction due to uncertain conductivity values.
AB  - This paper proposes a modification of the subspace correlation cost function and
      the Recursively Applied and Projected Multiple Signal Classification (RAP-MUSIC)
      method for electroencephalography (EEG) source analysis in epilepsy. This enables
      to reconstruct neural source locations and orientations that are less degraded
      due to the uncertain knowledge of the head conductivity values. An extended
      linear forward model is used in the subspace correlation cost function that
      incorporates the sensitivity of the EEG potentials to the uncertain conductivity
      value parameter. More specifically, the principal vector of the subspace
      correlation function is used to provide relevant information for solving the EEG
      inverse problems. A simulation study is carried out on a simplified spherical
      head model with uncertain skull to soft tissue conductivity ratio. Results show
      an improvement in the reconstruction accuracy of source parameters compared to
      traditional methodology, when using conductivity ratio values that are different
      from the actual conductivity ratio. 

PMID- 24111155
TI  - Adapting proportional myoelectric-controlled interfaces for prosthetic hands.
AB  - Powered hand prostheses with many degrees of freedom are moving from research
      into the market for prosthetics. In order to make use of the prostheses' full
      functionality, it is essential to find efficient ways to control their multiple
      actuators. Human subjects can rapidly learn to employ electromyographic (EMG)
      activity of several hand and arm muscles to control the position of a cursor on a
      computer screen, even if the muscle-cursor map contradicts directions in which
      the muscles would act naturally. We investigated whether a similar control
      scheme, using signals from four hand muscles, could be adopted for real-time
      operation of a dexterous robotic hand. Despite different mapping strategies,
      learning to control the robotic hand over time was surprisingly similar to the
      learning of two-dimensional cursor control. 

PMID- 24111156
TI  - Preliminary study on proportional and simultaneous estimation of hand posture
      using surface EMG based on synergy concept.
AB  - Most of current myoelectric prostheses are using sequential and on-off control
      strategy within pattern classification framework, which is of robustness. But it
      is not a natural neuromuscular control scheme. On the other hand, there are two
      difficulties to control the prosthesis proportionally and simultaneously. First,
      human hand is high dimensional with more than 20 degrees-of-freedom (DOFs);
      Second, extracting such control information from EMG is hard due to signal
      crosstalk and noises. This paper is aimed at proposing a new method for
      proportional and simultaneous myoelectric control, taking advantage of synergy
      concept. The hand motion and corresponding forearm EMG signals were collected
      simultaneously. Principal component analysis (PCA) is used to reduce hand motion
      dimension. And support vector regression (SVR) is adopted to build the connection
      between hand posture and EMG. Offline analysis validated the effectiveness of
      this method, and preliminary and positive results have been obtained. 

PMID- 24111157
TI  - Therapeutic effects of anti-spastic medication on neuromuscular abnormalities in
      SCI: a system identification approach.
AB  - Previous attempts to investigate the effects of antispastic medications are
      limited to clinical studies using that use clinical evaluations to assess. Since
      these measures are neither objective nor quantitative, the therapeutic effects of
      such medications on neuromuscular properties have not been fully evaluated. In
      this study, as a first attempt, we examined the effect of tizanidine, an anti
      spastic medication, on modification of the neuromuscular properties of patients
      with chronic incomplete spinal cord injury (SCI). Each patient was administered 2
      mg of tizanidine four times per day for four weeks. The spastic ankle of each
      patient was evaluated at baseline (prior to any medication, and then 1, 2, and 4
      weeks after the start of medication. The ankle was perturbed with a small
      amplitude Pseudo-Random Binary Sequence (PRBS) perturbation at various positions
      over the ankle range-of-motion. A parallel-cascade system identification
      technique, which provides an objective and quantitative measure of neuromuscular
      properties, was used to calculate the intrinsic and reflex stiffness. The
      stiffness vs. joint angle trends were then calculated for each evaluation; these
      curves were compared across the intervention time to determine the recovery
      pattern (i.e. change over time) due to the tizanidine intervention. All patients
      exhibited decreases in reflex stiffness (which abnormally increase after SCI) due
      to the medication; however, patients were observed to exhibit multiple recovery
      patterns. For some patients, the reflex stiffness continuously reduced over the
      four-week intervention period, while for other patients, the decrease during the
      first week (i.e. between the baseline and 1-Week evaluations) was most
      pronounced. Also, some patients presented a significant decrease with time, while
      others presented no improvement in the intrinsic stiffness. These findings
      suggest that tizanidine may be effective in reducing not only reflex stiffness,
      but also the subject's intrinsic stiffness for certain patients. Future work
      remains to identify predictors which can objectively determine which patients are
      likely to exhibit maximal benefit from the tizanidine prior to being prescribed
      with the medication. 

PMID- 24111158
TI  - Boundary integral formulation for the electrical response of a nerve to an
      extracellular stimulation.
AB  - We present a two-dimensional boundary integral formulation of nerve impulse
      propagation. A nerve impulse is a potential difference across the cellular
      membrane that propagates along the nerve fiber. The traveling transmembrane
      potential is produced by the transfer of ionic species between the intra- and
      extra-cellular mediums. This current flux across the membrane-composed of
      conduction, diffusion and capacitive terms- is regulated by passive and active
      mechanisms that are highly complicated to describe mathematically from a
      microscopic point of view. Based on the Hodgkin and Huxley axon model, we propose
      a well-posed integral formulation based on a quasi-static approximation amenable
      to time-stepping schemes and discuss first results. 

PMID- 24111159
TI  - Development of a linear induction motor based artificial muscle system.
AB  - We present the design of a linear induction motor based on electromagnetic
      interactions. The engine is capable of producing a linear movement from
      electricity. The design consists of stators arranged in parallel, which produce a
      magnetic field sufficient to displace a plunger along its axial axis.
      Furthermore, the winding has a shell and cap of ferromagnetic material that
      amplifies the magnetic field. This produces a force along the length of the motor
      that is similar to that of skeletal muscle. In principle, the objective is to use
      the engine in the development of an artificial muscle system for prosthetic
      applications, but it could have multiple applications, not only in the medical
      field, but in other industries. 

PMID- 24111160
TI  - Development of a monitoring system for physical frailty in independent elderly.
AB  - Frailty is of increasing concern due to the associated decrease in independence
      of elderly who suffer from the condition. An innovative system was designed in
      order to objectively quantify the level of frailty based on a series of remote
      tests, each of which used objects similar to those found in peoples' homes. A
      modified ball, known as the Grip-ball was used to evaluate maximal grip force and
      exhaustion during an entirely remote assessment. A smartphone equipped with a tri
      axial accelerometer was used to estimate gait velocity and physical activity
      level. Finally, a bathroom scale was used to assess involuntary weight loss. The
      smart phone processes all of the data generated, before it is transferred to a
      remote server where the user, their entourage, and any medical professionals with
      authorization can access the data. This innovative system could enable the onset
      of frailty to be detected early, thus giving sufficient time for a targeted
      intervention program to be implemented, thereby increasing independence for
      elderly users. 

PMID- 24111162
TI  - A dynamic perfusion bioreactor approach for engineering respiratory tissues in
      vitro.
AB  - In vitro culture of respiratory tissues poses many challenges due to the
      intrinsic complexity of the respiratory system. Multiple cellular phenotypes
      comprise the respiratory epithelium and operate under dynamic, gas-interchanging
      conditions that should be replicated for near-physiologic cultivation of
      functional tissues in vitro. A novel biomimetic perfusion bioreactor system has
      been proposed to reconstitute key functional conditions of the human lung. This
      portable system consists of several biologically-inspired components: (i) a 3
      dimensional (3-D) elastomeric soft tissue scaffold construct, (ii) a mechanical
      actuator, (iii) a perfusion system and (iv) gaseous exchange capabilities. These
      integrated components operate synergistically to create a unique, dynamic air
      liquid interface (ALI) environment that allows controlled application of
      physiological and pathological strain while complementing standard cell culture
      techniques. This system holds potential for engineering 3-D tissues to meet
      growing demand for a range of applications, from more ethical and efficient
      pharmaceutical screening to clinical graft transplants. 

PMID- 24111161
TI  - Portable bioreactor for perfusion and electrical stimulation of engineered
      cardiac tissue.
AB  - Cardiac tissue engineering aims to create functional tissue constructs that can
      reestablish the structure and function of injured myocardium. Although
      bioreactors have facilitated the engineering of cardiac patches of clinically
      relevant size in vitro, a major drawback remains the transportation of the
      engineered tissues from a production facility to a medical operation facility
      while maintaining tissue viability and preventing contamination. Furthermore,
      after implantation, most of the cells are endangered by hypoxic conditions that
      exist before vascular flow is established. We developed a portable device that
      provides the perfusion and electrical stimulation necessary to engineer cardiac
      tissue in vitro, and to transport it to the site where it will be implantated.
      The micropump-powered perfusion apparatus may additionally function as an
      extracorporeal active pumping system providing nutrients and oxygen supply to the
      graft post-implantation. Such a system, through perfusion of oxygenated media and
      bioactive molecules (e.g. growth factors), could transiently support the tissue
      construct until it connects to the host vasculature and heart muscle, after which
      it could be taken away or let biodegrade. 

PMID- 24111163
TI  - Effect of DMSO concentration, cell density and needle gauge on the viability of
      cryopreserved cells in three dimensional hyaluronan hydrogel.
AB  - For cells seeded in scaffolds, transplanted cell survival rate plays an important
      role for cell transplantation efficiency, and is essential for successful cell
      transplantation. Fibroblast viability in HyStem-C was examined by a double
      staining Live/Dead Viability/Cytotoxicity assay, and cell images were analyzed
      using MetaMorph software for calculating live cell percentage for fresh and
      cryopreserved cells at different incubation time points, delivery methods,
      differing DMSO and cell concentrations. The results of this research demonstrated
      that in HyStem-C, the viability of cryopreserved cells (85%) was significantly
      lower than fresh collected cells (96.7%). In addition, the physical force from a
      27 gauge needle significantly decreased frozen cell survival rates to 83-85%
      compared to pipette delivered cells. Higher DMSO concentration (1.0%) and higher
      cell density (2 * 10(7) per milliliter) also significantly decreased cell
      survival to 73%. Cryopreserved cell viability in three dimensional scaffolding
      can be maintained over 80% with cell density of 1 * 10(7) per milliliter, total
      DMSO concentration of 0.5%, and passed through a 27-gauge needle. These results
      demonstrate the viability of cells seeded in hyaluronan hydrogel with commonly
      used storage and delivery methods can bring rather satisfactory cell
      transplantation efficiency. 

PMID- 24111164
TI  - Analysis of the contraction of fibroblast-collagen gels and the traction force of
      individual cells by a novel elementary structural model.
AB  - Based on the experimental data of the contraction ratio of fibroblast-collagen
      gels with different initial collagen concentrations and cell numbers, we analyzed
      the traction force exerted by individual cells through a novel elementary
      structural model. We postulate that the mechanical mechanism of the gel
      contraction is mainly because that populated cells apply traction force to some
      of the surrounding collagen fibrils with such proper length potential to be
      pulled straight so as to be able to sustain the traction force; this traction
      induce the cells moving closely to each other and consequently compact the
      fibrillar network; the bending force of the fibrils in turn resists the movement.
      By employing fiber packing theory for random fibrillar networks and network
      alteration theory, the bending force of collagen fibrils was deduced. The
      traction force exerted by individual fibroblasts in the gels was balanced by the
      bending force and the resistance from interstitial fluid since inertial force can
      be neglected. The maximum traction force per cell under free floating condition
      is in the range of 0.27-9.02 nN depending on the initial collagen concentration
      and populated cell number. The most important outcome of this study is that the
      traction force of individual cells dynamically varies under different gel
      conditions, whereas the adhesion force between cell and individual fibrils is
      relatively converging and stable. 

PMID- 24111165
TI  - Development of a patient specific artificial tracheal prosthesis: design,
      mechanical behavior analysis and manufacturing.
AB  - There is a need to create patient specific organ replacements as there are
      differences in the anatomical dimensions among individuals. High failure rates in
      tracheal prosthesis are attributed to the lack of mechanical strength and
      flexibility, slow rate of growth of ciliated epithelium and leakage of
      interstitial fluid into the lumen. This paper proposes a methodology of design,
      simulations and fabrication of a patient specific artificial tracheal prosthesis
      for implantation to closely mimic the biomechanical properties of the natural
      trachea, and describes the prototype device and its materials. Results show that
      the patient-specific trachea prosthesis has mechanical properties approximate
      that of normal tracheal rings. The user centric tracheal prosthesis is
      demonstrated to be a promising candidate for tracheal replacement. 

PMID- 24111166
TI  - A case of successful interaction between cells derived from human ovarian
      follicular liquid and gelatin cryogel for biotech and medical applications.
AB  - Significant research efforts have been undertaken in the last decade to develop
      specific cell-based therapies and, in particular, adult multipotent mesenchymal
      stem cells (MSCs) hold great promise toward such regenerative strategies. Bio
      materials have been widely used in reconstructive bone surgery to heal critical
      size bone defects due to trauma, tumor resection, and tissue degeneration. In
      particular, gelatin cryogel scaffolds are promising new biomaterials owing to
      their biocompatibility. There is an increasing demand for MSC-based regenerative
      approaches in the musculoskeletal system. Combining stem cells with biomaterial
      scaffolds provides a promising strategy for tissue engineering. Our previous
      studies showed the possibility to obtain MSCs from the human ovarian follicular
      liquid (FL) that is usually wasted during in vitro fertilization (IVF). In this
      study, we tested the ability of these FL cells to grow on gelatin cryogel in
      comparison with MSCs derived from human bone marrow. Samples and controls were
      analyzed with confocal and scanning electron microscopes. Results demonstrated
      that FL cells could grow on the biomaterial not only on the top but also in the
      layers below till 60 um of deepness. Data suggested that the observed cells were
      mesenchymal since positive for vimentin and CD-44, typical MSC markers.
      Successful growth of putative MSCs derived from follicular liquid on 3D gelatin
      cryogel opens potential developments in biotech and medical applications. 

PMID- 24111167
TI  - 3-D robotic tele-surgery and training over next generation wireless networks.
AB  - The latest advances on robotic surgery enable the performance of many surgical
      procedures by utilizing minimally invasive techniques. In particular, recent 3-D
      endoscopes have improved the performance of minimally invasive surgical
      procedures. Based on these advances, performing or visualizing in real-time
      surgical procedures at a distance can be envisaged. In this paper, we present a
      performance evaluation of 3-D robotic tele-surgery and training over next
      generation wireless networks, namely wireless networks based on the long term
      evolution (LTE) 3GPP standard. Different scheduling strategies are compared and
      results are analyzed in term of the resulting quality of experience (QoE) for the
      surgeon. 

PMID- 24111168
TI  - An arc-length warping algorithm for gesture recognition using quaternion
      representation.
AB  - This paper presents a new algorithm, called Dynamic Arc-Length Warping algorithm
      (DALW) for hand gesture recognition based on the orientation data. In this
      algorithm, after calculating the quaternion for each orientation measurement, we
      use DALW algorithm to obtain a similarity measure between different trajectories.
      We present the benefits of using quaternion alongside the implementation of
      Dynamic Arc Length Warping to present an optimized tool for gesture
      recognition.We show the advantages of this approach compared with other
      techniques. This tool can be used to distinguish similar and different gestures.
      An experimental validation is carried out to classify a series of simple human
      gestures. 

PMID- 24111169
TI  - Assistance to bone milling: a tool mounted visual display improves the efficiency
      of robotic guidance.
AB  - In this paper, a new kind of assistance for bone milling is disclosed. It
      combines a robotic comanipulator applying forces to guide the milling tool tip
      with a visual display mounted on the hand-held tool. This visual display is a LED
      bargraph providing to the user a geometric information that is mostly redundant
      with the forces exerted by the robot, thus constituting a multi-modal feedback.
      Although very basic and rather inexpensive, the additional visual display is
      experimentally shown to significantly improve the precision of the gesture. 

PMID- 24111170
TI  - The effect of a robot-assisted surgical system on the kinematics of user
      movements.
AB  - Teleoperated robot-assisted surgery (RAS) offers many advantages over traditional
      minimally invasive surgery. However, RAS has not yet realized its full potential,
      and it is not clear how to optimally train surgeons to use these systems. We
      hypothesize that the dynamics of the master manipulator impact the ability of
      users to make desired movements with the robot. We compared freehand and
      teleoperated movements of novices and experienced surgeons. To isolate the
      effects of dynamics from procedural knowledge, we chose simple movements rather
      than surgical tasks. We found statistically significant effects of teleoperation
      and user expertise in several aspects of motion, including target acquisition
      error, movement speed, and movement smoothness. Such quantitative assessment of
      human motor performance in RAS can impact the design of surgical robots, their
      control, and surgeon training methods, and eventually, improve patient outcomes. 

PMID- 24111171
TI  - Development of a 6-DOF manipulator driven by flexible shaft for minimally
      invasive surgical application.
AB  - This paper presents a 6-DOF manipulator which consists of four parts, 1-DOF
      translational joint, two 2-DOF bending joints (segment1 and segment2), and 1-DOF
      rotational gripper. The manipulator with "flexible shaft and Double Screw Drive
      (DSD) mechanism" structure can obtain omni-directional bending motion through
      rotation of flexible shafts. In the first prototype, the flexible shafts were
      connected directly with the actuators in the manipulator. Compared with the first
      prototype, in the second prototype, flexible shafts for power transmission are
      connected to the base of the manipulator. Universal joints are used for power
      transmission to realize distal motion. The improvement done with the design of
      the second prototype reduced the torque necessary to drive the flexible shafts
      during motion in surgical interventions. Experiment results show that the
      manipulator has enough range of movement for surgical intervention. 

PMID- 24111172
TI  - A modular magnetic platform for Natural Orifice Transluminal Endoscopic Surgery.
AB  - Modern surgery is currently developing NOTES (Natural Orifice Translumenal
      Endoscopic Surgery) robotic approaches to enable scarless surgical procedures.
      Despite of the variegated devices proposed, they still have several limitations.
      In this work, we propose a surgical platform composed of specialized modules, in
      order to provide the overall system with adequate stability, dexterity and force
      generation. The concept behind the platform, the main modules and their
      performance are described to highlight the system potential to outperform current
      NOTES procedures. 

PMID- 24111173
TI  - A viscoelastic property study in canine liver before and after HIFU ablation in
      vitro.
AB  - Elasticity imaging techniques have shown great potential in detecting High
      Intensity Focused Ultrasound (HIFU) lesions based on their distinct biomechanical
      properties. However, quantitative tissue viscoelastic properties and the optimal
      power to obtain the best contrast parameters remain scarce. In the present study,
      fresh canine livers were ablated ex vivo using six different acoustic powers and
      time durations, covering an energy range of 80-330 J. Biopsy samples were then
      extracted and examined, using rheometry, to obtain the viscoelastic properties
      post-ablation in vitro. All mechanical parameters were found to be frequency
      dependent. Both the shear complex modulus and viscosity exhibited monotonic
      increase for the first 4 groups (80-240 J), relatively lower HIFU powers. Similar
      parameters from groups 5-6 (300-330 J) showed relative decrease, still higher
      than unablated group 0. The tangent of the stress-strain phase shift was found to
      vary from unablated group 0 to ablated groups 1-6. However, no measurable
      difference amongst the ablated groups was found. Decreased stiffening at high
      powers compared to the baseline could likely be due to compromised structural
      integrity in the pulverized tissue well beyond the boiling point. The findings
      here can be used to optimize the efficient monitoring and treatment of tumors
      using any thermally-based methods where strong tissue damage is expected and/or
      warranted, respectively. 

PMID- 24111174
TI  - Localized elasticity measurement for detection of coagulation during HIFU
      therapy.
AB  - High intensity focused ultrasound (HIFU) treatment is one minimally invasive
      treatment method for cancer. Visualizing the internal treatment area of a body
      during HIFU treatment is required in order to achieve appropriate beam
      positioning and HIFU dosage. The objective of this work is to develop an
      ultrasound monitoring system for thermally induced coagulation. Localized motion
      imaging (LMI) is a monitoring method used to detect a localized mechanical
      response that is dependent on changes in tissue stiffness caused by thermal
      coagulation. In LMI, amplitude modulated HIFU causes oscillation of tissues in
      the HIFU focal area. The elastic modulus at a coagulated area increases and can
      be detected as an area with decreased oscillation amplitude., Localized control
      of the oscillation by changing the modulation frequency was conducted to increase
      the detection sensitivity for small coagulated areas in porcine liver. 2 and 7.5
      MHz transducers were employed for HIFU and imaging, respectively. The amplitude
      modulation frequency was changed in the range from 50 to 200 Hz. The acoustic
      intensity of HIFU was 2.0 kW/cm2 at the focus and the exposure time was 45 s. The
      decrease in the amplitude of tissue oscillation at the focal point was detected
      within 5-10 s of HIFU exposure at the highest modulation frequency. The detected
      amplitude was decreased to 0.2, which indicates that for LMI, a high modulation
      frequency is suitable for the detection of small coagulation areas or areas of
      initial coagulation. 

PMID- 24111175
TI  - Active control of microbubbles stream in multi-bifurcated flow by using 2D phased
      array ultrasound transducer.
AB  - We have previously reported our attempt to propel microbbles in flow by a primary
      Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an
      obstacle along its direction of propagation. However, when ultrasound was emitted
      from surface of the body, controlling bubbles in against flow was needed. It is
      unpractical to use multiple transducers to produce the same number of focal
      points because single element transducer cannot produce more than two focal
      points. In this study, we introduced a complex artificial blood vessel according
      to a capillary model and a 2D array transducer to produce multiple focal points
      for active control of microbubbles in against flow. Furthermore, we investigated
      bubble control in viscous fluid. As the results, we confirmed clearly path
      selection of MBs in viscous fluid as well as in water. 

PMID- 24111176
TI  - Optimization of real-time acoustical and mechanical monitoring of high intensity
      focused ultrasound (HIFU) treatment using harmonic motion imaging for high
      focused ultrasound (HMIFU).
AB  - Harmonic Motion Imaging (HMI) for Focused Ultrasound (HMIFU) is a recently
      developed high-intensity focused ultrasound (HIFU) treatment monitoring method
      with feasibilities demonstrated in silica, in vitro and in vivo. Its principle is
      based on emission of an Amplitude-modulated therapeutic ultrasound beam utilizing
      a therapeutic transducer to induce an oscillatory radiation force while tracking
      the focal tissue mechanical response during the HIFU treatment using a confocally
      aligned diagnostic transducer. In order to translate towards the clinical
      implementation of HMIFU, a complete assessment study is required in order to
      investigate the optimal radiation force threshold for reliable monitoring the
      local tissue mechanical property changes, i.e., the estimation HMIFU displacement
      under thermal, acoustical, and mechanical effects within focal medium (i.e.,
      boiling, cavitation, and nonlinearity) using biological specimen. In this study,
      HMIFU technique is applied on HIFU treatment monitoring on freshly excised ex
      vivo canine liver specimens. In order to perform the multi-characteristic
      assessment, the diagnostic transducer was operated as either a pulse-echo imager
      or Passive Cavitation Detector (PCD) to assess the acoustic and mechanical
      response, while a bare-wire thermocouple was used to monitor the focal
      temperature change. As the acoustic power of HIFU treatment was ranged from 2.3
      to 11.4 W, robust HMI displacement was observed across the entire range.
      Moreover, an optimized range for high quality displacement monitoring was found
      to be between 3.6 to 5.2W, where displacement showed an increase followed by
      significant decrease, indicating a stiffening of focal medium due to thermal
      lesion formation, while the correlation coefficient was maintained above 0.95. 

PMID- 24111177
TI  - Production of acoustic field with multiple focal points to control high amount of
      microbubbles in flow using a 2D array transducer.
AB  - We have newly developed a 2D array transducer to control the behavior of
      microbubbles, which is different from that for HIFU therapy, to emit continuous
      wave by designing acoustic field including multiple focal points. In the
      experiment using a straight path model, we have confirmed that higher
      concentration of acoustic energy does not result more aggregation. We also have
      confirmed the trapped areas of microbubbles are located not in the peak of the
      distribution of sound pressure, but in the middle range. The dispersion of
      acoustic energy is important because there was a relation in the trapping
      performance of microbubbles and the shape of acoustic field. 

PMID- 24111178
TI  - Chemotherapy of glioblastoma by targeted liposomal platinum compounds with
      focused ultrasound.
AB  - Giloblastoma multiforme (GBM) is the most aggressive brain neoplasm, and patients
      have a poor prognosis after radiation and chemotherapy. The chemotherapy
      protocols still marginally improve the anti-tumor effect of patients with
      glioblastoma because the therapeutic dosage of many drugs is impeded by the blood
      brain barrier (BBB). The use of liposomal drugs to GBM treatment might benefit
      from a more crossing of the BBB due to the lipid nature achieving higher doses of
      drug at the tumor sites. Human GBM-bearing mice were injected intravenously with
      cisplatin encapsulated in atherosclerotic plaque-specific peptide-1 (AP-1)
      conjugated liposomes or unconjugated liposome. Moreover, the administration of AP
      1 liposomal cisplatin (lipoplatin) followed by focused ultrasound (FUS)-induced
      BBB disruption. Tumor progression was monitored by biophotonic imaging. The
      preliminary data demonstrated that the GBM chemotherapy with AP-1 lipoplatin
      followed by pulsed FUS showed a modest improvement of tumor growth in the brain
      compared to the group treated with lipoplatin alone. Further investigations are
      needed to use this new targeted lipoplatin in treatment of malignancies. 

PMID- 24111179
TI  - EEG-based upper-alpha neurofeedback for cognitive enhancement in major depressive
      disorder: a preliminary, uncontrolled study.
AB  - Conditioning of the upper-alpha rhythm to improve cognitive performance in
      healthy users by means of neurofeedback (NF) has been evaluated by several
      studies, however its effectiveness in people with severe cognitive deficits, such
      as depressive subjects, remains underexplored. This paper reports on a
      preliminary uncontrolled study to assess the effects of an upper-alpha NF
      intervention on patients with major depressive disorder (MDD). The NF effects on
      the EEG and cognitive performance were assessed. The EEG results showed that
      patients were able to modulate the upper-alpha rhythm in task-related EEG and
      during training, in both cases across the executions of the NF sessions, and pre
      and post within each session. The behavioral results showed the effectiveness of
      this intervention in a variety of cognitive functions such as working memory,
      attention, and executive functions. 

PMID- 24111180
TI  - Circadian variation of scalp EEG: a novel measure based on wavelet packet
      transform and differential entropy.
AB  - We propose a novel entropy-based measure to quantify the circadian variations of
      scalp electroencephalogram (EEG) by analyzing waking epochs of nap opportunities
      under an ultradian sleep-wake cycle (USW) protocol. To compute this circadian
      measure for a nap opportunity, each waking epoch (~1 sec) is decomposed using
      wavelet packet transform and the relative energy for the desired frequency band
      (here, 10-12 Hz) is calculated. Then, in a bootstrapping procedure, a shape
      statistic (skewness or kurtosis) of the relative energy distribution, after each
      resampling, is computed. Finally, the probability density function of this
      statistic is estimated, and the corresponding differential entropy is considered
      as the circadian measure. This measure was evaluated using EEG recordings from 4
      healthy subjects during a 72-h USW procedure. According to the results, the
      proposed measure showed a significant circadian variation both for individual and
      group data, with peak values occurring near the core body temperature minimum.
      The performance of the entropy-based measure was also compared with that of two
      other measures, namely mean energy logarithm and mean energy ratio, revealing the
      superiority of this measure.

PMID- 24111181
TI  - Hot Spot Hound: a novel robot-assisted platform for enhancing TMS performance.
AB  - Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that produces
      excitatory depolarization in the neurons located in the cerebral cortex. In order
      to proficiently stimulate a specific cerebral area it is of main importance the
      correct positioning and maintaining of the magnetic coil, while avoiding the
      mismatch due to subject head-coil relative movement. Hot Spot Hound is a novel
      robot-assisted experimental platform for enhancing TMS stimulation performance.
      It integrates a commercial optoelectronic neuronavigation system (E.M.S. srl,
      Italy) for gathering data on the relative pose (position and orientation) of
      subject's scalp and TMS coil, and a service robotic arm designed for human
      interaction (LWR system by KUKA, Germany). Besides integrating and synchronizing
      different platform sub-systems, we implement a control strategy to center the
      stimulation point and compensate for involuntary subject movements. Specifically,
      the proposed control maintains constant over time the homogeneous transformation
      matrix between the pose of the coil and of the head. The value of position
      stiffness has been chosen in order to assure the better compromise between coil
      position and orientation error, and the safety of the experimental subject. In
      this paper we show that Hot Spot Hound can provide coil position and orientation
      errors well beyond the ones achieved by manual experimenter, while assuring
      safety in the physical interaction with the stimulated subject.

PMID- 24111182
TI  - Seizure prediction with bipolar spectral power features using Adaboost and SVM
      classifiers.
AB  - This paper presents the results of our study on finding a lower complexity and
      yet a robust seizure prediction method using intracranial electroencephalogram
      (iEEG) recordings. We compare two classifiers: a low-complexity Adaboost and the
      more complex support vector machine (SVM). Adaboost is a linear classier using
      decision stumps, and SVM uses a nonlinear Gaussian kernel. Bipolar and/or time
      differential spectral power features of different sub-bands are extracted from
      the iEEG signal. Adaboost is used to simultaneously classify as well as rank the
      features. Eliminating the low discriminating features reduces computational
      complexity and power consumption. The top features selected by Adaboost were also
      used as a feature set for SVM classification. The outputs of classifiers are
      regularized by applying a moving-average window and a threshold is used to
      generate alarms. The proposed methods were applied on 8 invasive recordings
      selected from the EPILEPSIAE database, the European database of EEG seizure
      recordings. Doublecross validation is used by separating data sets for training
      and optimization from testing. The key conclusion is that Adaboost performs
      slightly better than SVM using a reduced feature set on average with
      significantly less complexity resulting in a sensitivity of 77.1% (27 of 35
      seizures in 873 h recordings) and a false alarm rate of 0.18 per hour.

PMID- 24111183
TI  - A boosted cascade for efficient epileptic seizure detection.
AB  - Seizure detection from electroencephalogram (EEG) plays an important role for
      epilepsy therapy. Due to the diversity of seizure EEG patterns between different
      individuals, multiple features are necessary for high accuracy since a single
      feature could hardly encode all types of epileptiform discharges. However, a
      large feature set inevitably causes the increase of the computational cost. This
      paper proposes a boosted cascade chain to obtain both high detection performance
      and high computational efficiency. Sixteen features that are widely used in
      seizure detection are implemented. Considering the sequential characteristics of
      EEG signals, the features are extracted on each 1-second segment and its former
      three segments. Thus, a total of 64 features are used to construct a feature
      pool. Based on the feature pool, Real AdaBoost is used to select a group of
      effective features, on which weak classifiers are learned to assemble a strong
      classifier. The strong classifier is transformed to a cascade classifier by
      reordering the weak classifiers and learning a threshold for each weak
      classifier. The cascade classifier still has the similar classification strength
      to the original strong classifier. More importantly, it is able to reject easy
      non-seizure samples by the first a few weak classifiers in the cascade, thus high
      computational efficiency can be obtained. To evaluate our method, 90.6-hour EEG
      signals from four patients are tested. The experimental results show that our
      method can achieve an average accuracy of 95.31% and an average detection rate of
      91.29% with the false positive rate of 4.68%. On average, only about 4 features
      are used. Compared with support vector machine (SVM), our method is much more
      efficient with the similar detection performance. 

PMID- 24111184
TI  - Quantitative EEG analysis in minimally conscious state patients during postural
      changes.
AB  - Mobilization and postural changes of patients with cognitive impairment are
      standard clinical practices useful for both psychic and physical rehabilitation
      process. During this process, several physiological signals, such as Electroen
      cephalogram (EEG), Electrocardiogram (ECG), Photopletysmography (PPG),
      Respiration activity (RESP), Electrodermal activity (EDA), are monitored and
      processed. In this paper we investigated how quantitative EEG (qEEG) changes with
      postural modifications in minimally conscious state patients. This study is quite
      novel and no similar experimental data can be found in the current literature,
      therefore, although results are very encouraging, a quantitative analysis of the
      cortical area activated in such postural changes still needs to be deeply
      investigated. More specifically, this paper shows EEG power spectra and brain
      symmetry index modifications during a verticalization procedure, from 0 to 60
      degrees, of three patients in Minimally Consciousness State (MCS) with focused
      region of impairment. Experimental results show a significant increase of the
      power in beta band (12 - 30 Hz), commonly associated to human alertness process,
      thus suggesting that mobilization and postural changes can have beneficial
      effects in MCS patients. 

PMID- 24111185
TI  - Effect of hypothermia on cortical and thalamic signals in anesthetized rats.
AB  - Beneficial effects of hypothermia on subjects with neuro-pathologies have been
      well demonstrated in both animal studies and clinical trials. Although it is
      known that temperature significantly impacts neurological injuries, the
      underlying mechanism remains unclear. We studied the effect of temperature
      modulation on neural signals in the cortex and the thalamus in uninjured brains
      of anesthetized rats. Six rats were divided into a hypothermic (32 to 34  degrees
      C, n=3) and a hyperthermic group (38.5 to 39.5  degrees C, n=3). EEG, and
      extracellular signals from somatosensory cortex and the ventral posterolateral
      nucleus of thalamus were recorded at different temperature phases (normothermia
      (36.5 to 37.5  degrees C) and hypothermia or hyperthermia). During hypothermia,
      similar burst suppression (BS) patterns were observed in cortical and thalamic
      signals as in EEG, but thalamic activity was not completely under suppression
      when both EEG and cortical signals were electrically silent. In addition, our
      results showed that hypothermia significantly increased the burst suppression
      ratio (BSR) in EEG, cortical and thalamic signals by 3.42, 3.25, 7.29 times
      respectively (P<0.01), and prolonged the latency of neuronal response in cortex
      to median nerve stimulation from 9 ms to 16 ms (P<0.01). Furthermore, during
      normothermia, the correlation coefficient between thalamic and cortical signals
      was 0.35+/-0.02 while during hypothermia, it decreased to 0.16+/-0.03 with
      statistical significance (P<0.01). These results can potentially assist in better
      understanding the effects of hypothermia.

PMID- 24111186
TI  - A simple and effective semi-invasive method for inducing local hypothermia in rat
      spinal cord.
AB  - Hypothermia has been shown to be an effective treatment for spinal cord injury.
      Local hypothermia is advantageous because it avoids inducing systemic side
      effects of general hypothermia while providing the opportunity for greater
      temperature reduction at the site of injury, which may contribute to increased
      neuroprotection. We report a new semi-invasive method for inducing local
      hypothermia in rats' spinal cords. Our method does not require laminectomy or
      penetration of the dura and is more effective at cooling the cord than
      transcutaneous approaches. We show that we were successfully able to cool the
      spinal cord to 30.2 +/- 0.3 degrees C for 2 hours with rectal temperature
      maintained at 37.3 +/- 0.3 degrees C after a spinal cord contusion injury. We
      also validated our method in control rats that received only a laminectomy.
      Furthermore, this method was able to reliably cool and rewarm the cord at a
      steady rate (Delta5.5 degrees C in 30 min, or 0.2 degrees C/min). Future work
      will include validating long-term functional improvements of injured rats after
      treatment and to apply local cooling to other spinal cord injury models, such as
      compression injuries.

PMID- 24111187
TI  - Source activation during facial emotion perception correlates with positive and
      negative symptoms scores of schizophrenia.
AB  - Schizophrenia is one of the most devastating of all mental illnesses, and has
      dimensional characteristics that include both positive and negative symptoms. One
      problem reported in schizophrenia patients is that they tend to show deficits in
      face emotion processing, on which negative symptoms are thought to have stronger
      influence. In this study, four event-related potential (ERP) components (P100,
      N170, N250, and P300) and their source activities were analyzed using EEG data
      acquired from 23 schizophrenia patients while they were presented with facial
      emotion picture stimuli. Correlations between positive and negative syndrome
      scale (PANSS) scores and source activations during facial emotion processing were
      calculated to identify the brain areas affected by symptom scores. Our analysis
      demonstrates that PANSS positive scores are negatively correlated with major
      areas of the left temporal lobule for early ERP components (P100, N170) and with
      the right middle frontal lobule for a later component (N250), which indicates
      that positive symptoms affect both early face processing and facial emotion
      processing. On the other hand, PANSS negative scores are negatively correlated
      with several clustered regions, including the left fusiform gyrus (at P100), most
      of which are not overlapped with regions showing correlations with PANSS positive
      scores. Our results suggest that positive and negative symptoms affect
      independent brain regions during facial emotion processing, which may help to
      explain the heterogeneous characteristics of schizophrenia. 

PMID- 24111188
TI  - Characteristics of sympathetic nerve activity in the rat sciatic nerve in
      response to microstimulation in a sympathetic fascicle in the contralateral side.
AB  - Microneurography is used for the monitor of various peripheral nerve activities.
      We recently reported that the electrical stimulation of peripheral sympathetic
      nerve fascicle via the microelectrode, i.e., microstimulation, temporarily
      reduced the blood glucose level in rats in case that the stimulation intensity
      was set high enough to induce small muscle contraction. However, the nature of
      microstimulation has little been clarified yet. Therefore, in the present study,
      we first detected sympathetic nerve signal microneurographically in the bilateral
      sciatic nerves of rats, and one of the microelectrodes was used for the
      microstimulation (0.25 ms-width pulse train at a rate of 1 Hz) while sympathetic
      nerve activity (SNA) was recorded in the contralateral side as a parameter of
      systemic sympathetic effects. The SNA, expressed as action potential rate, was
      transiently increased 150 ms after each stimulation pulse in case that the
      stimulation intensity was set not less than -0.1 V from the contraction threshold
      (around 0.32 V). To confirm that the increase was not caused by the activation of
      low threshold, thick fibers such as motor nerves in the vicinity of the
      microelectrode tip, next, a bipolar hook electrode, instead of the
      microelectrode, was then used in the stimulation side. As a result, the above
      mentioned, transient increase in SNA was not observed any more in the
      contralateral side. These results suggest that systemic SNA could be enhanced
      with lower stimulation intensity than that inducing muscle contraction, and that
      thicker fibers may little affect the increase in the contralateral SNA. 

PMID- 24111189
TI  - Absence seizure epilepsy detection using linear and nonlinear EEG analysis
      methods.
AB  - In this study, we investigated three measures capable of detecting absence
      seizures with increased sensitivity based on different underlying assumptions.
      Namely, an information-based method known as Approximate Entropy, a nonlinear
      alternative (Order Index), and a linear variance analysis approach. The results
      on the long-term EEG data suggest increased accuracy in absence seizure detection
      achieving sensitivity as high as 97.33% with no further application of any
      sophisticated classification scheme. 

PMID- 24111190
TI  - Using decision trees to measure activities in people with stroke.
AB  - Improving community mobility is a common goal for persons with stroke. Measuring
      daily physical activity is helpful to determine the effectiveness of
      rehabilitation interventions. In our previous studies, a novel wearable shoe
      based sensor system (SmartShoe) was shown to be capable of accurately classify
      three major postures and activities (sitting, standing, and walking) from
      individuals with stroke by using Artificial Neural Network (ANN). In this study,
      we utilized decision tree algorithms to develop individual and group activity
      classification models for stroke patients. The data was acquired from 12
      participants with stroke. For 3-class classification, the average accuracy was
      99.1% with individual models and 91.5% with group models. Further, we extended
      the activities into 8 classes: sitting, standing, walking, cycling, stairs-up,
      stairs-down, wheel-chair-push, and wheel-chair-propel. The classification
      accuracy for individual models was 97.9%, and for group model was 80.2%,
      demonstrating feasibility of multi-class activity recognition by SmartShoe in
      stroke patients. 

PMID- 24111191
TI  - Classification of stand-to-sit and sit-to-stand movement from low frequency EEG
      with locality preserving dimensionality reduction.
AB  - Recent studies have demonstrated decoding of lower extremity limb kinematics from
      noninvasive electroencephalography (EEG), showing feasibility for development of
      an EEG-based brain-machine interface (BMI) to restore mobility following
      paralysis. Here, we present a new technique that preserves the statistical
      richness of EEG data to classify movement state from time-embedded low frequency
      EEG signals. We tested this new classifier, using cross-validation procedures,
      during sit-to-stand and stand-to-sit activity in 10 subjects and found decoding
      accuracy of greater than 95% on average. These results suggest that this
      classification technique could be used in a BMI system that, when combined with a
      robotic exoskeleton, can restore functional movement to individuals with
      paralysis. 

PMID- 24111192
TI  - Cortical activation pattern for grasping during observation, imagery, execution,
      FES, and observation-FES integrated BCI: an fNIRS pilot study.
AB  - Passive movement, action observation and motor imagery as well as motor execution
      have been suggested to facilitate the motor function of human brain. The purpose
      of this study is to investigate the cortical activation patterns of these four
      modes using a functional near-infrared spectroscopy (fNIRS) system. Seven healthy
      volunteers underwent optical brain imaging by fNIRS. Passive movements were
      provided by a functional electrical stimulation (FES). Results demonstrated that
      while all movement modes commonly activated premotor cortex, there were
      considerable differences between modes. The pattern of neural activation in motor
      execution was best resembled by passive movement, followed by motor imagery, and
      lastly by action observation. This result indicates that action observation may
      be the least preferred way to activate the sensorimotor cortices. Thus, in order
      to show the feasibility of motor facilitation by a brain computer interface (BCI)
      for an extreme case, we paradoxically adopted the observation as a control input
      of the BCI. An observation-FES integrated BCI activated sensorimotor system
      stronger than observation but slightly weaker than FES. This limitation should be
      overcome to utilize the observation-FES integrated BCI as an active motor
      training method. 

PMID- 24111193
TI  - An fMRI-compatible multi-configurable handheld response system using an intensity
      modulated fiber-optic sensor.
AB  - Functional magnetic resonance imaging (fMRI) data should be interpreted in
      combination and in the context of relevant behavioral measurements. However, the
      strong magnetic environment of MRI scanner and the supine position of
      participants in the scanner significantly limit how participants' behavioral
      responses are recorded. This paper presents the design of a low-cost handheld
      response system (HRS) with a multi-configurable optomechanical design that
      utilizes a reflective-type intensity modulated fiber-optic sensor (FOS) and a
      programmable visual interface to accurately gather participants' behavioral
      responses during an fMRI experiment. Considering the effects of an input unit
      design on the participants' performance efficiency across age groups and physical
      and neurological (dis)ability, the optomechanical system is designed to provide
      flexibility in the range of an input module with easy change-out feature.
      Specifically, the input unit can be configured as a binary module such as push
      buttons or as an analog input device including a scrolling wheel, and one
      dimensional joystick (lever arm). To achieve MRI-compatibility, all parts of the
      unit that are used inside the scanner bore are built from nonferromagnetic and
      off-the-shelf plastic materials. The MRI compatibility was evaluated on a 3.0
      Tesla MRI scanner running echo planar imaging (EPI) and the average time-variant
      signal-to-noise ratio (tSNR) loss is limited to 2%. 

PMID- 24111194
TI  - Passive ankle dorsiflexion by an automated device and the reactivity of the motor
      cortical network.
AB  - Gait impairment is an important consequence of neurological disease. Passive
      mobilization of the affected lower limbs is often prescribed in order to
      safeguard tissue properties and prevent circulatory sequelae during paresis.
      However, passive movement could play a role also in stimulating cortical areas of
      the brain devoted to the control of the lower limb, so that deafferentation and
      learned non-use can be contrasted. The purpose of the present work is to
      investigate cortical involvement during active and passive movements of the ankle
      joint, in an attempt to gain deeper insight in the similarities between these two
      conditions. A wearable device to mobilize the ankle joint was implemented
      utilizing rotary shape memory alloy actuators. The technical characteristics of
      this actuator make it very compatible with the tight limitations on
      electromagnetic noise imposed by diagnostic instrumentation. Eleven healthy
      volunteers took part in the pre-clinical phase of the study. According to the
      protocol, brain activity was recorded by 165-channel magnetoencephalography (MEG)
      under three different conditions: rest, active dorsiflexion of the ankle and
      passive mobilization of the same joint. The acquired data were processed to
      obtain cortical ERD/ERS (Event Related Desynchronization/ Synchronization) maps,
      which were then compared. The results of this analysis show that there are
      similar patterns of activity between active and passive movement, particularly in
      beta band, in the contralateral primary sensorimotor, dorsal premotor and
      supplementary motor areas. This result, albeit obtained from healthy subjects,
      might suggest that passive motion provides somatosensory afferences that, to some
      extent, are processed in a similar manner as for voluntary control. Should this
      evidence be confirmed by further experiments on neurological patients, it could
      support the prescription of passive exercise as a surrogate of active workout, at
      least, so long as patients are paretic. 

PMID- 24111195
TI  - Multi-dipole EEG source localization using particle swarm optimization.
AB  - The multi-dipole EEG source localization problem is (usually) highly nonlinear
      with a non-convex cost function. Moreover, the gray matter tissue is located in
      several disjunct regions in the head which leads to a non-continuous solution
      space. For solving this problem an efficient algorithm which can handle multi
      source activities is needed. In this paper, a modified particle swarm
      optimization (MPSO) method is proposed to solve the multi-dipole EEG source
      localization. The method is tested on synthetic EEG signals generated from two
      strong active sources and a noisy background source. The results show that using
      the new method is a reliable choice when we deal with a strong multi-active
      source scenario, in which a single dipole source localization may fail. 

PMID- 24111196
TI  - Modular, bluetooth enabled, wireless electroencephalograph (EEG) platform.
AB  - A design for a modular, compact, and accurate wireless electroencephalograph
      (EEG) system is proposed. EEG is the only non-invasive measure for neuronal
      function of the brain. Using a number of digital signal processing (DSP)
      techniques, this neuronal function can be acquired and processed into meaningful
      representations of brain activity. The system described here utilizes Bluetooth
      to wirelessly transmit the digitized brain signal for an end application use. In
      this way, the system is portable, and modular in terms of the device to which it
      can interface. Brain Computer Interface (BCI) has become a popular extension of
      EEG systems in modern research. This design serves as a platform for applications
      using BCI capability. 

PMID- 24111197
TI  - CortiQ - clinical software for electrocorticographic real-time functional mapping
      of the eloquent cortex.
AB  - Planning for epilepsy surgery depends substantially on the localization of brain
      cortical areas responsible for sensory, motor, or cognitive functions, clinically
      also known as eloquent cortex. In this paper, we present the novel software
      package 'cortiQ' that allows clinicians to localize eloquent cortex, thus
      providing a safe margin for surgical resection with a low incidence of
      neurological deficits. This software can be easily used in addition to
      traditional mapping procedures such as the electrical cortical stimulation (ECS)
      mapping. The software analyses task-related changes in gamma activity recorded
      from implanted subdural electrocorticography electrodes using extensions to
      previously published methods. In this manuscript, we describe the system's
      architecture and workflow required to obtain a map of the eloquent cortex. We
      validate the system by comparing our mapping results with those acquired using
      ECS mapping in two subjects. Our results indicate that cortiQ reliably identifies
      eloquent cortex much faster (several minutes compared to an hour or more) than
      ECS mapping. Next-neighbour analyses show that there are no false positives and
      an average of 1.24% false negatives. 

PMID- 24111198
TI  - Predicting rTMS effect for deciding stimulation parameters.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is used in the medical field
      to modulate cortical excitability. However, when applied in this setting, rTMS
      stimulation parameters are not usually decided objectively. The aim of this study
      is to make a model that predicts the rTMS effect, allowing stimulation parameters
      (intensity and pulse number) to be easily determined before use. First, we
      investigated the relationship between stimulation condition and rTMS outcome.
      rTMS delivered at 1 Hz was applied with stimulation intensities of 85%, 100%, or
      115% resting motor threshold (RMT) over the primary motor cortex in the left
      hemisphere. Motor-evoked potentials (MEPs) were measured before rTMS and after
      every 200 rTMS pulses. Eighteen hundred pulses were applied for each stimulation
      condition. Results showed that more pulses and stronger intensities lead to a
      larger decrease in MEP amplitude. An initial prediction model was then made by
      applying multiple regression analysis over the experimental data. We then
      adjusted the model depending on the size of the initial MEP amplitude before
      rTMS, and confirmed the improvement. 

PMID- 24111199
TI  - Inhibitory interference to abandonment of voluntary finger movement by single
      pulse transcranial magnetic stimulation.
AB  - Brain function dynamics related to an inhibitory interference in voluntary motor
      abandonment was investigated with single-pulse transcranial magnetic stimulation
      (TMS) and electroencephalogram (EEG). As the voluntary motor movement, a point-to
      point reaching movement of the right index-finger was conducted. The starting
      time of the movement was indicated with the clock making one revolution for 4 s.
      The time the clock hand passed the 9 o'clock position was defined as a go-signal.
      In the go trials, the subject was instructed to start the movement at the timing
      of the go signal. In some trials, called as pre-stop trials, a stop signal was
      presented with red LED illumination -100 ms from the timing of the go-signal. The
      go-trials and pre-stop trials were randomly performed in the series of the
      trials. In all trials, TMS or sham-TMS were conducted. TMS was delivered with a
      round coil on the subject's head at various timings. Sham-TMS trials were with a
      click sound of TMS produced by another coil located near the head without the
      brain stimulation. In the sham-TMS trials of the pre-stop trials, the subject was
      able to prevent the finger movement. However, the TMS conducted at -150, -100 or 
      50 ms from the go-signal induced the involuntary finger movement in the pre-stop
      trials. We also measured brain potentials in the sham-TMS and TMS trials. The
      potential at Fz electrode showed a large positive peak in the sham-TMS trials of
      the pre-stop trials, whereas the potentials at the same latency were attenuated
      in the TMS trials of the pre-stop trials. These results indicated that the single
      pulse TMS applied around the stop-signal in the reaching finger movement could
      intervene in the brain function of the voluntary motor abandonment conducted at
      medial frontal cortex. 

PMID- 24111200
TI  - Thermophysiological responses induced by a body heat removal system with Peltier
      devices in a hot environment.
AB  - Individuals with spinal cord injuries often experience thermoregulation disorders
      as well as sensory and motor disabilities. In order to prevent such individuals
      from becoming hyperthermic, we developed a body heat removal system (BHRS) with
      thermoelectric devices. Our BHRS comprises four Peltier devices mounted on a
      wheelchair backrest and continuously transfers body heat through the contacting
      interface to the external environment. Here, we characterized thermophysiological
      responses induced by this novel contact-type cooling system. A cooling experiment
      in a hot environment with five able-bodied subjects demonstrated that sweating
      and systolic blood pressure in the back-cooling (BC) trial were significantly
      suppressed compared with those in no-cooling (NC) trial, while no difference was
      found in oral and skin temperatures. A correlation was observed between chest
      skin temperature and blood flow in the NC trial; this was not observed in the BC
      trial. These results suggest that BHRS modulates normal thermoregulatory
      responses, including sweating and vascular dilation and has the capability to
      partly replace these functions. 

PMID- 24111201
TI  - Changes in behavior of evoked potentials in the brain as a possible indicator of
      fatigue in people.
AB  - Many professions place significant mental and/or physical strain on their
      workers. Some professionals (such as firefighters, soldiers, and pilots) have an
      inherent responsibility for the safety of others. Making sure that workers in
      these remain fit for duty is an important health/safety concern for the workers
      and those they serve. This paper explores the viability of using EEG as a non
      invasive, cost efficient method for assessing fatigue, sleep deprivation,
      physical exertion and stress. Specifically, P300 evoked potentials are generated
      in response to certain stimuli. Variations in the response characteristics
      (magnitude, shape, and peak shift) are explored in relation to sleep deprivation,
      caffeine usage, and physical exertion. Preliminary data suggests that there are
      quantifiable changes to the P300 response that may be attributed to fatigue. 

PMID- 24111202
TI  - Seated balance during pitch motion with and without visual input.
AB  - The study of seated balance and postural control, specifically in relation to
      wheelchair propulsion, has been an area of interest for quite some time. In
      biomedical and rehabilitation research this has led to the potential of treatment
      and prevention of spinal cord and musculoskeletal injuries. To date, little study
      has been done which analyzes the activity of lower trunk muscles for seated
      balance, as opposed to upper limb and shoulder muscles. For the purpose of this
      study, motorized rotational movement in the forward and backward directions was
      simulated and the corresponding lower back and abdominal muscle activity was
      recorded by surface electromyography (EMG). A comparison of how muscle activity
      was affected by visual input was also conducted. This pilot study was performed
      on two healthy individuals, recording two of their abdominal muscles, and two
      lower back muscles. Electrodes were placed on the right and left rectus
      abdominis, external oblique, thoracic erector spinae, and lumbar erector spinae.
      Each trial consisted of twelve randomized tests that were performed twice on each
      subject. The results showed that the speed of rotational motion was the dominant
      factor in abdominal muscle activity. The results also suggested that motion of
      the subject with respect to the visual display had an inhibitory effect on the
      motion perception. Furthermore, challenges to wheelchair patients on a slightly
      rough terrain were highlighted. Finally, the results also suggested that visual
      effects during rotational motion had a small effect on the subject, which was
      possibly caused by placing focus on something else rather than on balance issues.

PMID- 24111203
TI  - Body movement analysis during sleep for children with ADHD using video image
      processing.
AB  - In recent years, the amount of children with sleep disorders that cause arousal
      during sleep or light sleep is increasing. Attention-deficit hyperactivity
      disorder (ADHD) is a cause of this sleep disorder; children with ADHD have
      frequent body movement during sleep. Therefore, we investigated the body movement
      during sleep of children with and without ADHD using video imaging. We analysed
      large gross body movements (GM) that occur and obtained the GM rate and the rest
      duration. There were differences between the body movements of children with ADHD
      and normally developed children. The children with ADHD moved frequently, so
      their rest duration was shorter than that of the normally developed children.
      Additionally, the rate of gross body movement indicated a significant difference
      in REM sleep (p < 0.05). In the future, we will develop a new device that can
      easily diagnose children with ADHD, using video image processing.

PMID- 24111204
TI  - Development of a network system combined with ambulatory and non-conscious
      physiological measurements for supporting challenged kids - a new proposal of a
      gait monitoring system for use in rehabilitation.
AB  - Various physiological measurement techniques have been developed to support
      healthcare and daily living of adult including elderly. However, in light of the
      rapid growth of the declining birth rate, promotion in care and life support for
      children are not enough. Especially in rehabilitation for disabled children,
      i.e., challenged kids, it is important for therapist to evaluate the efficacy of
      rehabilitation and the health condition. Share of these information with
      educational, welfare, and government institutions are also needed for accurate
      life support. Therefore, the quantitative data of the activities and daily health
      status are helpful. From these viewpoints, we are developing a new network system
      for monitoring the activities and the health status of children using ambulatory
      and non-conscious physiological measurements as well as data browse at anytime
      and anywhere. Firstly, we propose a wearable gait monitoring system to support
      evaluation for the efficacy of rehabilitation. In this study, the present system
      can successfully detect the characteristics of postural changes in children with
      disorder of movement, demonstrating its usefulness and availability to the
      evaluation for the effect of the brace attached to the subject's lower limb. 

PMID- 24111205
TI  - Measurement of attention during movement: acquisition of ambulatory EEG and
      cognitive performance from healthy young adults.
AB  - Non-invasive methods of recording human electro-cortical brain dynamics during
      normal daily activities would have far-reaching clinical benefits. The literature
      suggests a strong link between gait and cognition, where attention is seen to
      play a central role. This study investigated if clinically useful
      electrophysiological measures of attention can be collected using an auditory
      oddball task in ecological/non-clinic environments through analysis of the
      amplitude and latency of auditory P3 event related potentials (ERPs).
      Electrophysiological (EEG, EOG, EMG) recordings were taken for 7 healthy subjects
      while presented with an auditory oddball task. Data was recorded in control,
      static (seated) and dynamic (fixed cycling) experimental conditions. Recordings
      were also taken for two subjects during treadmill walking. P3 ERPs were
      calculated and data analysis showed that peak amplitude and component latency
      remained stable across all experimental conditions. For the Cz electrode position
      there were 0.2-2% P3 amplitude and 3-9% P3 latency differences. P3 amplitude and
      latency also remained stable between experimental conditions for all electrode
      locations. This result opens up the possibility to quantitatively investigate the
      interaction between gait and attention during the ageing process but also in
      movement disorders such as freezing of gait in Parkinson's disease. 

PMID- 24111206
TI  - Automatic detection of the wake and stage 1 sleep stages using the EEG sub-epoch
      approach.
AB  - Studies by Rechtschaffen and Kales (R&K), rely on 30-sec epochs to score sleep
      stages. In this paper, we introduce a new approach based on three consecutive and
      non-consecutive 6-sec sub-epochs for the detection of the wake stage and stage 1
      sleep. The Relative Spectral Energy Band (RSEB) is used as a feature extraction
      from the electroencephalographic (EEG) signal. Spectral estimation is performed
      using non-parametric and parametric methods. We then compared the performance of
      the conventional 30-sec epochs with the three consecutive and non-consecutive 6
      sec epochs. The outcomes of this study showed that while the accuracy varies
      between subjects, the non-parametric method proved to be more effective with
      stage 1 sleep detection and the parametric method was more effective for wake
      stage detection. The non-consecutive sub-epoch method was more effective and
      consecutive method was least effective in non-parametric stage 1 detection.
      Alternatively, the 30-second epoch method was most effective for parametric wake
      stage detection. 

PMID- 24111208
TI  - Main disease classification of intermittent claudication via L1-regularized SVM.
AB  - There are multiple diseases that cause intermittent claudication, including
      lumber spinal canal stenosis (LSS) and peripheral arterial disease (PAD). LSS is
      categorized on the basis of the diseased part: L4 and L5. The medical treatment
      for these groups is totally different and the differentiation is important. With
      this in mind, we examined walking-motion data for patients and derived several
      features for the differentiation in previous studies. However, these features
      were not specialized for classification, and there is no guarantee that the
      features are effective for real differentiation. The present study investigates
      the possibility of differentiation by gait analysis, via use of an L1-regularized
      support vector machine (SVM). An L1-regularized SVM can execute both
      classification and feature selections simultaneously. On the basis of this
      method, our paper presents the methodology for classifying the underlying disease
      of the intermittent claudication with an accuracy of 79.7%. In addition, new
      effective features for the differentiation are extracted. 

PMID- 24111207
TI  - Does 3D produce more symptoms of visually induced motion sickness?
AB  - 3D stereoscopy technology with high quality images and depth perception provides
      entertainment to its viewers. However, the technology is not mature yet and
      sometimes may have adverse effects on viewers. Some viewers have reported
      discomfort in watching videos with 3D technology. In this research we performed
      an experiment showing a movie in 2D and 3D environments to participants.
      Subjective and objective data are recorded and compared in both conditions.
      Results from subjective reporting shows that Visually Induced Motion Sickness
      (VIMS) is significantly higher in 3D condition. For objective measurement, ECG
      data is recorded to find the Heart Rate Variability (HRV), where the LF/HF ratio,
      which is the index of sympathetic nerve activity, is analyzed to find the changes
      in the participants' feelings over time. The average scores of nausea,
      disorientation and total score of SSQ show that there is a significant difference
      in the 3D condition from 2D. However, LF/HF ratio is not showing significant
      difference throughout the experiment. 

PMID- 24111209
TI  - Electrotactile vision substitution for 3D trajectory following.
AB  - Navigation for blind persons represents a challenge for researchers in vision
      substitution. In this field, one of the used techniques to navigate is guidance.
      In this study, we develop a new approach for 3D trajectory following in which the
      requested task is to track a light path using computer input devices (keyboard
      and mouse) or a rigid body handled in front of a stereoscopic camera. The light
      path is visualized either on direct vision or by way of a electro-stimulation
      device, the Tongue Display Unit, a 12 * 12 matrix of electrodes. We improve our
      method by a series of experiments in which the effect of the modality of
      perception and that of the input device. Preliminary results indicated a close
      correlation between the stimulated and recorded trajectories.

PMID- 24111210
TI  - Development of body weight support gait training system using pneumatic Mckibben
      actuators -control of lower extremity orthosis.
AB  - Recently, robot assisted therapy devices are increasingly used for spinal cord
      injury (SCI) rehabilitation in assisting handicapped patients to regain their
      impaired movements. Assistive robotic systems may not be able to cure or fully
      compensate impairments, but it should be able to assist certain impaired
      functions and ease movements. In this study, the control system of lower
      extremity orthosis for the body weight support gait training system which
      implements pneumatic artificial muscle (PAM) is proposed. The hip and knee joint
      angles of the gait orthosis system are controlled based on the PAM coordinates
      information from the simulation. This information provides the contraction data
      for the mono- and bi-articular PAMs that are arranged as posterior and anterior
      actuators to simulate the human walking motion. The proposed control system
      estimates the actuators' contraction as a function of hip and knee joint angles.
      Based on the contraction model obtained, input pressures for each actuators are
      measured. The control system are performed at different gait cycles and two PMA
      settings for the mono- and bi-articular actuators are evaluated in this research.
      The results showed that the system was able to achieve the maximum muscle moment
      at the joints, and able to perform the heel contact movement. This explained that
      the antagonistic mono- and bi-articular actuators worked effectively. 

PMID- 24111211
TI  - Prediction functional independence measure in hip fracture patients.
AB  - The importance of early inclusion in rehabilitation program and exercise of older
      people after the hip fracture could be explained by the fact that physical
      activity influences the muscle strength, balance and eventually degree of hip
      pain [11]. Such determinants are very important particularly for individuals
      quality of life and could prevent further risks of comorbidities and falls later
      in life. It has been often hypothesized that the success of recovery is extremely
      dependent on the timeliness and adequacy of the treatment. While it is desirable
      to provide the best possible care as soon as possible the actual limitations that
      may exist in health-care systems due to a limited number of medical staff as well
      as limited capacity in rehabilitation programs may create need for appropriate
      planning and/or scheduling. 

PMID- 24111212
TI  - Electrical impedance tomography reconstruction through simulated annealing with
      multi-stage partially evaluated objective functions.
AB  - The EIT reconstruction problem can be solved as an optimization problem using
      Simulated Annealing. Different objective functions have already been used:
      Euclidian distance between the simulated and observed potentials; total least
      squares error minimization. The objective function was partially evaluated in
      both methods. In this paper, a new image reconstruction method that combines the
      best characteristics from both described methods is proposed. The total
      reconstruction cost is smaller when compared to each method using one objective
      function alone. A denser reconstruction mesh is used, and a regularization is
      adopted by adding a new term similar to the first-order Tikhonov functional. The
      impact of the regularization in the previous two methods is also analyzed. 

PMID- 24111213
TI  - FEM electrode refinement for electrical impedance tomography.
AB  - Electrical Impedance Tomography (EIT) reconstructs images of electrical tissue
      properties within a body from electrical transfer impedance measurements at
      surface electrodes. Reconstruction of EIT images requires the solution of an
      inverse problem in soft field tomography, where a sensitivity matrix, J, of the
      relationship between internal changes and measurements is calculated, and then a
      pseudo-inverse of J is used to update the image estimate. It is therefore clear
      that a precise calculation of J is required for solution accuracy. Since it is
      generally not possible to use analytic solutions, the finite element method (FEM)
      is typically used. It has generally been recommended in the EIT literature that
      FEMs be refined near electrodes, since the electric field and sensitivity is
      largest there. In this paper we analyze the accuracy requirement for FEM
      refinement near electrodes in EIT and describe a technique to refine arbitrary
      FEMs. 

PMID- 24111215
TI  - Experimental implementation of a new method of imaging anisotropic electric
      conductivities.
AB  - This paper presents the first experiment of imaging anisotropic impedance using a
      novel technique called Diffusion Tensor Current Density Impedance Imaging (DTCD
      II). A biological anisotropic tissue phantom was constructed and an experimental
      implementation of the new method was performed. The results show that DT-CD-II is
      an effective way of non-invasively measuring anisotropic conductivity in
      biological media. The cross-property factor between the diffusion tensor and the
      conductivity tensor has been carefully determined from the experimental data, and
      shown to be spatially inhomogeneous. The results show that this novel imaging
      approach has the potential to provide valuable new information on tissue
      properties. 

PMID- 24111214
TI  - Evaluation of anomaly detection algorithm using trans-admittance mammography with
      60 * 60 electrode array.
AB  - Electrical impedance imaging has a potential to detect an early stage of breast
      cancer due to higher admittivity values compared with those of normal breast
      tissues. Specially, tumor size and extent of axillary lymph node involvement are
      important parameters to evaluate the breast cancer survival rate. We applied the
      anomaly detection algorithm to the high density trans-admittance mammography
      system for estimating the size and position of breast cancer. We tested 4
      different size of anomaly with 3 different conductivity contrasts at 5 different
      depths. From a frequency difference trans-admittance map, we can readily observe
      the transversal position and estimate its size and depth. However, the size
      estimation was dependent on the admittivity contrast between anomaly and
      background. It requires the robust detection algorithm regardless of the
      conductivity contrast. 

PMID- 24111216
TI  - Bladder volume estimation from electrical impedance tomography.
AB  - Ubiquitous knowledge of bladder volume is of great interest to patients whose
      perception of bladder volume is impaired. A promising approach to provide
      frequent bladder volume estimates to the patient are automatic and noninvasive
      measurements by electrical impedance tomography (EIT). Previous studies have
      shown a linear correlation of abdominal electrical impedance and bladder volume.
      In this article, we present two methods to extract a volume estimate from EIT
      measurements. One method is based on the global impedance from a reconstructed
      image, the second method is based on a singular value decomposition of the raw
      voltage measurement vector. A performance evaluation in presence of noise is
      performed. 

PMID- 24111217
TI  - Simulation of a current source with a Cole-Cole load for multi-frequency
      electrical impedance tomography.
AB  - An accurate current source is one of the keys in the hardware of Electrical
      impedance Tomography systems. Limitations appear mainly at higher frequencies and
      for non-simple resistive loads. In this paper, we simulate an improved Howland
      current source with a Cole-Cole load. Simulations comparing two different op-amps
      (THS4021 and OPA843) were performed at 1 kHz to 1 MHz. Results show that the
      THS4021 performed better than the OPA843. The current source with THS4021 reaches
      an output impedance of 20 MOmega at 1 kHz and above 320 kOmega at 1 MHz, it
      provides a constant and stable output current up to 4 mA, in the complete range
      of frequencies, and for Cole-Cole (resistive and capacitive) load. 

PMID- 24111218
TI  - Cortical surface reconstruction based on MEG data and spherical harmonics.
AB  - Estimates of coefficients of a spherical harmonic Fourier decomposition of the
      cortical surface can be obtained solely using MEG/EEG data and free energy as
      objective function. A stochastic methodology based on a Metropolis Search
      followed by a Bayesian Model Averaging is proposed to reconstruct cortical
      anatomy based functional information. 

PMID- 24111219
TI  - Mobile Health (mHealth) biomedical imaging paradigm.
AB  - Technology assisted methods for medical diagnosis and biomedical health
      monitoring are rapidly shifting from classical invasive methods to handheld-based
      non-invasive approaches. Biomedical imagining is one of the most prominent
      practices of non-invasive mechanisms in medical applications. This paper
      considers the medical imaging schemes for Mobile Health (mHealth) applications
      and studies the feasibility of future mobile systems for accommodating image
      informatics capabilities. 

PMID- 24111220
TI  - Potential of hybridization methods to reducing the dimensionality for
      multispectral biological images.
AB  - We address the problem of unsupervised band reduction in multispectral imagery.
      We propose to use a new hybridization of dimensionality reduction method by
      combining two categories of bands selection method with projection method and
      apply it to multispectral data. The algorithm employs the concepts of fuzziness
      and belongingness (Fuzzy K-means) to provide a better and more adaptive
      clustering process. However, the Fuzzy hybridized algorithm is applicable to
      medical imagery. A cluster validity function associated with Bezdek's partition
      coefficient is employed for evaluation of the dimension reduction's performance
      for this multispectral data. Experiments conducted in this paper confirm the
      feasibility of the new hybridization for multispectral dimensionality reduction
      and shows the potential of the proposed approach. 

PMID- 24111221
TI  - Compression of the CT images using classified energy and pattern blocks.
AB  - In this work, a new biomedical image compression method is proposed based on the
      classified energy and pattern blocks (CEPB). CEPB based compression method is
      specifically applied on the Computed Tomography (CT) images and the evaluation
      results are presented. Essentially, the CEPB is uniquely designed and structured
      codebook which is located on the both the transmitter and receiver part of a
      communication system in order to implement encoding and decoding processes. The
      encoding parameters are block scaling coefficient (BSC) and the index numbers of
      energy (IE) and pattern blocks (IP) determined for each block of the input images
      based on the CEPB. The evaluation results show that the newly proposed method
      provides considerable image compression ratios and image quality. 

PMID- 24111222
TI  - Fusion of multinuclear magnetic resonance images of knee for the assessment of
      articular cartilage.
AB  - The onset of osteoarthritis (OA), a most common knee joint disease, can be
      characterized by the degeneration of articular cartilage (AC). Degenerative
      changes in AC have been assessed by the morphological and physiological
      measurements using non-invasive modality such as Magnetic Resonance Imaging (MRI)
      to obtain MRI images of the knee. However, visualization and quantification of AC
      from MR images is difficult due to the low visibility contrast of AC compared to
      surrounding tissues, low and varying signal intensities in cartilage region and
      variable intensities in different slices of single dataset. In this work, we
      present a method to fuse multinuclear ((23)Na and (1)H) MR images acquired in the
      same plane without changing the position of the human knee as well as the Radio
      Frequency (RF) coil. This work is performed towards our hypothesis that fusion of
      sodium and proton images will provide an enhanced image that can be used for an
      accurate assessment of cartilage morphology. Our result shows that merging of
      sodium knee MR image with proton knee MR image resulting in enhanced contrast
      information in the cartilage region and resolves low visibility and varying
      intensities issue with 2D/3D proton MR. We conclude that the proposed method can
      further be utilized for the accurate assessment of cartilage morphology. 

PMID- 24111223
TI  - Visualization of pulsatile CSF motion separated by membrane-like structure based
      on four-dimensional phase-contrast (4D-PC) velocity mapping.
AB  - This work was performed to indicate the usefulness of magnetic resonance (MR) 4
      dimentional phase contrast (4D-PC) technique in assessing CerebroSpinal Fluid
      (CSF) motion in comparison with the time-Spatial Labeling Inversion Pulse (Time
      SLIP) technique. 4D-velocity vector, their curl, and, pressure gradient were
      evaluated in both flow phantom, and normal volunteers and a patient with
      hydrocepharus. The velocity and pressure gradient fields obtained by the 4D-PC
      technique were useful to visualize the CSF dynamics under the presence of a
      membrane-like structure, unlike the Time-SLIP in which the spin travel was
      visualized. Quantitative property was another advantage of the 4D-PC. The curl
      and the pressure gradient fields obtained with actual units should help
      clinicians to classify the conditions of the patients with CSF disorders. 

PMID- 24111224
TI  - Development of 3-D ultrasound system for assessment of adolescent idiopathic
      scoliosis (AIS): and system validation.
AB  - Adolescent idiopathic scoliosis (AIS) is a common spinal disease and the
      prevalence of AIS is 2 to 4 % of the youngsters in the United States. Radiograph
      based Cobb's method is regarded as the gold standard. AIS patients normally have
      to undergo regular X-ray assessment every 4 to 6 months until skeletal maturity
      is reached. Because of radiation hazard, X-ray images cannot be taken frequently,
      and thus it is difficult to perform close monitoring for the disease progression
      and treatment outcomes. In this study, a free-hand 3D ultrasound imaging system
      has been successfully developed for the radiation-free assessment of AIS. A
      series of B-mode ultrasound images with their spatial information were exploited
      to form a spine model for measuring the spine curvature. Sixteen spine phantoms
      with different simulated deformity were scanned by both conventional X-ray
      imaging and the 3D ultrasound system. The results showed that there was a strong
      correlation (R(2) = 0.759) between the Cobb's angles obtained by the two methods.
      The results also demonstrated a very good intra- and inter-observer
      reproducibility with ICC of 0.99 and 0.89, repectively. The findings suggest that
      it is feasible to use 3D ultrasound imaging for the assessment of scoliosis and
      deserves further clinical tests on patients with spine deformity. 

PMID- 24111225
TI  - Predicting a multi-parametric probability map of active tumor extent using random
      forests.
AB  - Glioblastoma Mulitforme is highly infiltrative, making precise delineation of
      tumor margin difficult. Multimodality or multi-parametric MR imaging sequences
      promise an advantage over anatomic sequences such as post contrast enhancement as
      methods for determining the spatial extent of tumor involvement. In considering
      multi-parametric imaging sequences however, manual image segmentation and
      classification is time-consuming and prone to error. As a preliminary step toward
      integration of multi-parametric imaging into clinical assessments of primary
      brain tumors, we propose a machine-learning based multi-parametric approach that
      uses radiologist generated labels to train a classifier that is able to classify
      tissue on a voxel-wise basis and automatically generate a tumor segmentation. A
      random forests classifier was trained using a leave-one-out experimental
      paradigm. A simple linear classifier was also trained for comparison. The random
      forests classifier accurately predicted radiologist generated segmentations and
      tumor extent. 

PMID- 24111227
TI  - Automatic distance measurement of abdominal aorta for ultrasonography-based
      visceral fat estimation.
AB  - Ultrasonography-based visceral fat estimation is a promising method to assess
      central obesity, which is associated with metabolic syndrome. The key to this
      method is to measure three types of distance in the ultrasound image. The most
      important one is the distance from the skin surface to the posterior wall of the
      abdominal aorta. We present a novel automatic measurement method to calculate
      this distance using 1D ultrasound signal processing. It is different from the
      conventional 2D image processing based methods which have high failure rate when
      the target is blurred or partially imaged. The proposed method identifies the
      waveforms of the aorta along a group of ultrasound scan lines and a rating
      mechanism is introduced to choose the best waveform for distance calculation. The
      robustness and accuracy of the method were evaluated by experiments based on
      clinical data. 

PMID- 24111226
TI  - Improved detection of landmarks on 3D human face data.
AB  - Craniofacial researchers make heavy use of established facial landmarks in their
      morphometric analyses. For studies on very large facial image datasets, the
      standard approach of manual landmarking is very labor intensive. With the goal of
      producing 20 established landmarks, we have developed a geometric methodology
      that can automatically locate 10 established landmark points and 7 other
      supporting points on human 3D facial scans. Then, to improve accuracy and produce
      all 20 landmarks, a deformable matching procedure establishes a dense
      correspondence from a template 3D mesh with a full set of 20 landmarks to each
      individual 3D mesh. The 17 geometrically-determined points on the individual 3D
      mesh are used for the initial correspondence required by the deformable matching.
      The method is evaluated on 115 3D facial meshes of normal adults, and results are
      compared to landmarks manually identified by medical experts. Our results show a
      marked improvement to prior results in the recent literature. 

PMID- 24111228
TI  - Measures of radial correlation and trend for classification of breast masses in
      mammograms.
AB  - In this paper, a novel approach for classification of breast masses is presented
      that quantifies the texture of masses without relying on accurate extraction of
      their contours. Two novel feature descriptors based on 2D extensions of the
      reverse arrangement (RA) and Mantel's tests were designed for this purpose.
      Measures of radial correlation and radial trend were extracted from the original
      gray-scale values as well as from the Gabor magnitude response of 146 regions of
      interest, including 120 benign masses and 26 malignant tumors. Four classifiers,
      Fisher-linear discriminant analysis, Bayesian, support vector machine, and an
      artificial neural network based on radial basis functions (ANN-RBF), were
      employed to predict the diagnosis, using stepwise logistic regression for feature
      selection and the leave-one-patient-out method for cross-validation. The ANN-RBF
      resulted in an area under the receiver operating characteristic curve of 0.93.
      The experimental results show the effectiveness of the proposed approach. 

PMID- 24111229
TI  - Automatic cropping method of chest radiographs based on adaptive binarization.
AB  - General radiography systems are widely used for medical diagnoses. Since the size
      of image detectors of general radiography systems is standardized in several
      fixed sizes, relative size of target body parts differs according to patients.
      The spread of digitization of X-ray imaging forces radiological technologists to
      crop radiographs manually after measurement for suitable use on diagnoses. This
      cropping operation distracts attention of radiological technologists from
      measurement operations and from care to patients. The purpose of this study is to
      establish image processing method to achieve automatic cropping of X-ray images,
      which reduces the radiological technologists' burden in general radiography
      workflow. The proposed method utilizes adaptive binarization as pre-processing of
      radiographs. In this paper, we show the result of the proposed method applied for
      chest radiographs and the evaluation by radiological technologists. 

PMID- 24111230
TI  - Protective jacket enabling decision support for workers in cold climate.
AB  - The cold and harsh climate in the High North represents a threat to safety and
      work performance. The aim of this study was to show that sensors integrated in
      clothing can provide information that can improve decision support for workers in
      cold climate without disturbing the user. Here, a wireless demonstrator
      consisting of a working jacket with integrated temperature, humidity and activity
      sensors has been developed. Preliminary results indicate that the demonstrator
      can provide easy accessible information about the thermal conditions at the site
      of the worker and local cooling effects of extremities. The demonstrator has the
      ability to distinguish between activity and rest, and enables implementation of
      more sophisticated sensor fusion algorithms to assess work load and pre-defined
      activities. This information can be used in an enhanced safety perspective as an
      improved tool to advice outdoor work control for workers in cold climate. 

PMID- 24111231
TI  - Performances evaluation of piezoresistive fabric sensors as function of yarn
      structure.
AB  - This work focus on the characterization of piezoresistive fabric sensors,
      realized with conductive yarns that are similar in term of conductive components,
      but different only in term of geometry, the yarns have been realized according
      two different production processes while the sensors have been produced following
      the same process, fabric structure and same materials. The different geometry of
      the yarns affects dramatically conductivity and functionality of the sensors in
      term of sensitivity and hysteresis minimization. This result confirms that the
      functional components can be engineered during the different phases of the
      process production; to get new properties and new applications. Small changes at
      fibers level can be fundamental to improve the properties of the fabric sensors. 

PMID- 24111232
TI  - Fabric-based pressure sensor array for decubitus ulcer monitoring.
AB  - Decubitus ulcers occur in an estimated 2.5 million Americans each year at an
      annual cost of $11 billion to the U.S. health system. Current screening and
      prevention techniques for assessing risk for decubitus ulcer formation and
      repositioning patients every 1-2 hours are labor-intensive and can be subjective.
      We propose use of a Bluetooth-enabled fabric-based pressure sensor array as a
      simple tool to objectively assess and continuously monitor decubitus ulcer risk. 

PMID- 24111233
TI  - Performances evaluation of textile electrodes for EMG remote measurements.
AB  - This work focus on the evaluation of textile electrodes for EMG signals
      acquisition. Signals have been acquired simultaneously from textile electrode and
      from gold standard electrodes, by using the same acquisition system; tests were
      done across subjects and with multiple trials to enable a more complete analysis.
      This research activity was done in the frame of the European Project Interaction,
      aiming at the development of a system for a continuous daily-life monitoring of
      the functional performance of stroke survivors in their physical interaction with
      the environment. 

PMID- 24111234
TI  - Multilevel analysis of calcium dynamics in stimulated cultures of cardiomyocytes.
AB  - We present an automatic method to characterize calcium activity in a culture of
      cardiac cells from a sequence of microscopy fluorescence images. The approach
      quantifies both the response of each individual cell in the culture to external
      field stimulation and the propagation properties of calcium wave-fronts, thus
      providing complementary information at different physiological levels. The
      technique classifies the response of each cell as regular or irregular based on a
      set of dynamical and morphological features of the calcium transients. Isochronal
      maps were constructed from the local activation times across the culture, and the
      front propagation was classified as planar or non-planar. The method has been
      applied to a set of 35 experiments, and the results indicate a significative
      connection between irregular behavior at the single-cell level and irregular
      front propagation. 

PMID- 24111235
TI  - On identification of sinoatrial node in zebrafish heart based on functional time
      series from optical mapping.
AB  - As a vertebrate cardiovascular model, the zebrafish heart has been used
      extensively in physiology research to study cardiac development and human cardiac
      disease. Optical mapping techniques provide an effective approach to record
      action potential propagation in the zebrafish heart. However, manual analysis of
      functional time series recorded from optical mapping can be laborious and time
      consuming. In this paper, a novel pipeline is proposed to assist physiologists in
      identifying the sinoatrial node (SAN) in zebrafish heart based on functional time
      series. First, the original optical mapping data are enhanced and averaged. Next,
      the heart is divided into small regions, and representative average time series
      are calculated. A 'discretization of derivative' (DoD) process is performed to
      model physiological similarity between signals. Finally, grouping is done on the
      DoD transformed representation, which is found to produce physiologically
      meaningful classification for SAN identification. 

PMID- 24111237
TI  - Graph theoretical connectivity analysis of the human brain while listening to
      music with emotional attachment: feasibility study.
AB  - Benefits of listening to music with emotional attachment while recovering from a
      cerebral ischemic event have been reported. To develop a better understanding of
      the effects of music listening on the human brain, an algorithm for the graph
      theoretical analysis of functional magnetic resonance imaging (fMRI) data was
      developed. From BOLD data of two paradigms (block-design, first piece: music
      without emotional attachment, additional visual guidance by a moving cursor in
      the score sheet; second piece: music with emotional attachment), network graphs
      were constructed with correlations between signal time courses as edge weights.
      Functional subunits in these graphs were identified with the MCODE clustering
      algorithm and mapped back into anatomical space using AFNI. Emotional centers
      including the right amygdala and bilateral insula were activated by the second
      piece (emotional attachment) but not by the first piece. Network clustering
      analysis revealed two separate networks of small-world property corresponding to
      task-oriented and resting state conditions, respectively. Functional subunits
      with highest interactions were bilateral precuneus for the first piece and left
      middle frontal gyrus and right amygdala, bilateral insula, left middle temporal
      gyrus for the second piece. Our results indicate that fMRI in connection with
      graph theoretical network analysis is capable of identifying and differentiating
      functional subunits in the human brain when listening to music with and without
      emotional attachment. 

PMID- 24111236
TI  - Resting state inter and intra hemispheric human brain functional connectivity.
AB  - Resting-state functional connectivity between neuroanatomical regions has
      attracted significant attention in recent years. In the process of obtaining the
      resting-state functional connectivity map of the human brain from blood-oxygen
      level-dependent fMRI signals, it is common to average the signals from left and
      right hemispheres. This averaging can introduce unappreciated complexities and
      unintended consequences not related to the research question of interest. In this
      paper, we mathematically demonstrate that measures of functional connectivity
      obtained by averaging homologous regions from the both hemispheres become
      undesirably dependent on four inter-hemispheric connectivity measures. We explore
      this finding in real-world fMRI data from 25 healthy young participants. We show
      that inter-hemispheric averaging has a mixed effect on the results and may
      introduce correlation artifacts to the connectivity map. Furthermore, we show
      mathematically and demonstrate with Monte Carlo simulations of null data that
      inter-hemispheric averaging will not alter human brain connectivity map at rest
      only and if only there are no inter-hemispheric correlations. 

PMID- 24111238
TI  - Atlas image labeling of subcortical structures and vascular territories in brain
      CT images.
AB  - We propose a multi-atlas labeling method for subcortical structures and cerebral
      vascular territories in brain CT images. Each atlas image is registered to the
      query image by a non-rigid registration and the deformation is then applied to
      the labeling of the atlas image to obtain the labeling of the query image. Four
      label fusion strategies (single atlas, most similar atlas, major voting, and
      STAPLE) were compared. Image similarity values in non-rigid registration were
      calculated and used to select and rank atlases. Major voting fusion strategy gave
      the best accuracy, with DSC (Dice similarity coefficient) around 0.85 +/- 0.03
      for caudate, putamen, and thalamus. The experimental results also show that
      fusing more atlases does not necessarily yield higher accuracy and we should be
      able to improve accuracy and decrease computation cost at the same time by
      selecting a preferred set with the minimum number of atlases. 

PMID- 24111239
TI  - Identification of brain white matter regions for diagnosis of Alzheimer using
      Diffusion Tensor Imaging.
AB  - Diffusion Tensor Imaging (DTI) technique is widely used to probe the white matter
      (WM) tracts, which is affected most by neurological disorders. The fractional
      anisotropy (FA) metric has been used predominantly to study changes in the WM
      tracts. Here an attempt is made to delineate specific regions of interest in the
      WM that may be probable indicators for the diagnosis of Alzheimer disease (AD).
      Genetic algorithm has been used as feature reduction method along with Adaptive
      Boosting (AdaBoost) machine learning technique to determine the most prominent
      regions in the WM that are indicators of AD. It is found in this study that
      Fornix region of WM is most affected by Alzheimer. Further, classification was
      done to differentiate between Alzheimer and Normal controls with accuracy of
      84.5%. The results obtained were validated by comparing with the existing
      literature on Alzheimer. 

PMID- 24111240
TI  - Cell-specific modeling of retinal ganglion cell electrical activity.
AB  - Variations in ionic channel expression and anatomical properties can influence
      how different retinal ganglion cell (RGC) types process synaptic information.
      Computational modeling approaches allow us to precisely control these biophysical
      and physical properties and isolate their effects in shaping RGC firing patterns.
      In this study, three models based on realistic representations of RGC
      morphologies were used to simulate the contribution of spatial structure of
      neurons and membrane ion channel properties to RGC electrical activity. In all
      simulations, the RGC models shared common ionic channel kinetics, differing only
      in their regional ionic channel distributions and cell morphology. 

PMID- 24111241
TI  - A continuum neuronal tissue model based on a two-compartmental representation of
      cells.
AB  - Although significant advances have been made in continuum modeling of cardiac and
      smooth muscle tissue, the progress in neuronal continuum modeling has been
      slower. In this paper, a continuum neuronal tissue model based on a two
      compartmental representation of cells is presented. Each neuron is described
      using both a somatic compartment modeled by the classical Hodgkin-Huxley current
      kinetics and a dendritic compartment based on a passive RC formulation. In
      addition, a synaptic current is fed into the dendritic compartment to account for
      the presynaptic influence of cells located within the dendritic field of each
      soma. A number of cases are simulated, including intracellular current injection
      into either the dendritic or somatic compartments, as well as extracellular
      current stimulation with and without synaptic input into neurons. The model
      incorporates a number of parameters controlling neuronal excitability which can
      be adjusted to validate each neuron's responses against experimental data,
      allowing for the modeling of different neuronal cell types and behaviors. 

PMID- 24111242
TI  - A simplified biophysical cell model for gastric slow wave entrainment simulation.
AB  - Gastric electrical activity, also termed slow wave activity, is generated by a
      class of pacemaker cells called the interstitial cells of Cajal (ICC), which are
      organized with decreasing intrinsic frequencies along the stomach. In the healthy
      stomach, slow waves of different intrinsic frequencies converge to a single
      frequency with a constant phase-lag, in a process called entrainment. The main
      aim of this study was to develop a simplified biophysical ICC model that is
      capable of modeling the self-excitatory behavior and standard morphology of
      gastric slow waves. Entrainment of gastric slow waves was simulated in a one
      dimensional (1D) model, with a linear gradient of intrinsic slow wave
      frequencies. In a coupled 1D model, the simulated slow waves were entrained to a
      single frequency; whereas in an uncoupled 1D model, the simulated slow waves
      occurred at different frequencies, resulting in loss of entrainment. The new cell
      model presents an option for future large multi-scale simulations of gastric slow
      waves in intact ICC network and diseased conditions where the loss of entrainment
      may lead to slow wave dysrhythmias and diminished gastric motility. 

PMID- 24111243
TI  - Modeling intrinsic electrophysiology of AII amacrine cells: preliminary results.
AB  - In patients who have lost their photoreceptors due to retinal degenerative
      diseases, it is possible to restore rudimentary vision by electrically
      stimulating surviving neurons. AII amacrine cells, which reside in the inner
      plexiform layer, split the signal from rod bipolar cells into ON and OFF cone
      pathways. As a result, it is of interest to develop a computational model to aid
      in the understanding of how these cells respond to the electrical stimulation
      delivered by a prosthetic implant. The aim of this work is to develop and
      constrain parameters in a single-compartment model of an AII amacrine cell using
      data from whole-cell patch clamp recordings. This model will be used to explore
      responses of AII amacrine cells to electrical stimulation. Single-compartment
      Hodgkin-Huxley-type neural models are simulated in the NEURON environment.
      Simulations showed successful reproduction of the potassium currentvoltage
      relationship and some of the spiking properties observed in vitro. 

PMID- 24111244
TI  - A model of evoked potentials in spinal cord stimulation.
AB  - Electrical stimulation of the spinal cord is used for pain relief, and is in use
      for hundreds of thousands of cases of chronic neuropathic pain. In spinal cord
      stimulation (SCS), an array of electrodes is implanted in the epidural space of
      the cord, and electrical currents are used to stimulate nearby nerve fibers,
      believed to be in the dorsal columns of the cord. Despite the long history of SCS
      for pain, stretching over 30 years, its underlying mechanisms are poorly
      understood, and the therapy has evolved very little in this time. Recent work has
      resulted in the ability to record complex compound action potential waveforms
      during therapy. These waveforms reflect the neural activity evoked by the
      therapeutic stimulation, and reveal information about the underlying
      physiological processes. We aim to simulate these processes to the point of
      reproducing these recordings. We establish a hybrid model of SCS, composed of a
      three dimensional electrical model and a neural model. The 3D model describes the
      geometry of the spinal regions under consideration, and the electric fields that
      result from any flow of current within them. The neural model simulates the
      behaviour of spinal nerve fibers, which are the target tissues of the therapy.
      The combination of these two models is used to predict which fibers may be
      recruited by a given stimulus, as well as to predict the ensuing recorded
      waveforms. The model is shown to reproduce major features of spinal compound
      action potentials, such as threshold and propagation behaviour, which have been
      observed in experiments. The model's coverage of processes from stimulation to
      recording allows it to be compared side-by-side with actual experimental data,
      and will permit its refinement to a substantial level of accuracy.

PMID- 24111245
TI  - Novel Spiking Neuron-Astrocyte Networks based on nonlinear transistor-like models
      of tripartite synapses.
AB  - In this paper a novel and efficient computational implementation of a Spiking
      Neuron-Astrocyte Network (SNAN) is reported. Neurons are modeled according to the
      Izhikevich formulation and the neuron-astrocyte interactions are intended as
      tripartite synapsis and modeled with the previously proposed nonlinear transistor
      like model. Concerning the learning rules, the original spike-timing dependent
      plasticity is used for the neural part of the SNAN whereas an ad-hoc rule is
      proposed for the astrocyte part. SNAN performances are compared with a standard
      spiking neural network (SNN) and evaluated using the polychronization concept,
      i.e., number of co-existing groups that spontaneously generate patterns of
      polychronous activity. The astrocyte-neuron ratio is the biologically inspired
      value of 1.5. The proposed SNAN shows higher number of polychronous groups than
      SNN, remarkably achieved for the whole duration of simulation (24 hours). 

PMID- 24111246
TI  - Pulse rate variability compared with Heart Rate Variability in children with and
      without sleep disordered breathing.
AB  - Heart Rate Variability (HRV), the variation of time intervals between heartbeats,
      is one of the most promising and widely used quantitative markers of autonomic
      activity. Traditionally, HRV is measured as the series of instantaneous cycle
      intervals obtained from the electrocardiogram (ECG). In this study, we
      investigated the estimation of variation in heart rate from a
      photoplethysmography (PPG) signal, called pulse rate variability (PRV), and
      assessed its accuracy as an estimate of HRV in children with and without sleep
      disordered breathing (SDB). We recorded raw PPGs from 72 children using the Phone
      Oximeter, an oximeter connected to a mobile phone. Full polysomnography including
      ECG was simultaneously recorded for each subject. We used correlation and Bland
      Altman analysis for comparing the parameters of HRV and PRV between two groups of
      children. Significant correlation (r > 0.90, p < 0.05) and close agreement were
      found between HRV and PRV for mean intervals, standard deviation of intervals
      (SDNN) and the root-mean square of the difference of successive intervals
      (RMSSD). However Bland-Altman analysis showed a large divergence for LF/HF ratio
      parameter. In addition, children with SDB had depressed SDNN and RMSSD and
      elevated LF/HF in comparison to children without SDB. In conclusion, PRV provides
      the accurate estimate of HRV in time domain analysis but does not reflect precise
      estimation for parameters in frequency domain. 

PMID- 24111247
TI  - Synchronisation and coupling analysis: applied cardiovascular physics in sleep
      medicine.
AB  - Sleep is a physiological process with an internal program of a number of well
      defined sleep stages and intermediate wakefulness periods. The sleep stages
      modulate the autonomous nervous system and thereby the sleep stages are
      accompanied by different regulation regimes for the cardiovascular and
      respiratory system. The differences in regulation can be distinguished by new
      techniques of cardiovascular physics. The number of patients suffering from sleep
      disorders increases unproportionally with the increase of the human population
      and aging, leading to very high expenses in the public health system. Therefore,
      the challenge of cardiovascular physics is to develop highly-sophisticated
      methods which are able to, on the one hand, supplement and replace expensive
      medical devices and, on the other hand, improve the medical diagnostics with
      decreasing the patient's risk. Methods of cardiovascular physics are used to
      analyze heart rate, blood pressure and respiration to detect changes of the
      autonomous nervous system in different diseases. Data driven modeling analysis,
      synchronization and coupling analysis and their applications to biosignals in
      healthy subjects and patients with different sleep disorders are presented. Newly
      derived methods of cardiovascular physics can help to find indicators for these
      health risks. 

PMID- 24111248
TI  - Estimating sleep disordered breathing based on heart rate analysis.
AB  - Heart rate variability and the analysis of the ECG with ECG derived respiration
      has been used to diagnose sleep disordered breathing. Recently it was possible to
      distinguish obstructive sleep apnea and central sleep apnea. This can be achieved
      by analyzing both, heart rate variability and the more mechanically induced ECG
      derived respiration in parallel. In addition the analysis of cardiopulmonary
      coupling facilitates to predict the personal risk factor for cardiovascular
      disorders. The analysis of heart rate, ECG and respiration goes beyond this
      analysis. Some studies indicate that it is possible to derive sleep stages from
      these signals. In order to derive sleep stages a more complex analysis of the
      signals is applied taking into account non-linear properties by using methods of
      statistical physics. To extract coupling information supports the distinction
      between sleep stages. Results are reported in this review. 

PMID- 24111249
TI  - Estimating relative respiratory effort from features of Photo-Plethysmography
      signal.
AB  - The gold standard method for measuring respiratory effort (esophageal pressure
      measurement) is invasive, uncomfortable, and itself can disrupt sleep. As a
      consequence, majority of sleep studies use an alternate sensor, typically
      respiratory bands, which, however, do not measure respiratory effort. Typically
      they indicate changes in thoracic volume, and so are more a secondary sensor of
      respiratory movement rather than respiratory effort. In this study, we aim to
      look at how features extracted from finger Photo Plethysmogram (PPG) signals
      correlate with changes in esophageal pressure signal. Principle component
      analysis was used to derive the relative respiratory effort signals using pulse
      to pulse intervals, pulse wave amplitudes, area of pulse and wavelet decomposed
      band (0.15~0.4 Hz) of PPG signals.

PMID- 24111250
TI  - Methods for heart rate variability analysis during sleep.
AB  - In the last years we have witnessed the growing interest in the heart rate
      variability (HRV) signal analysis during sleep. The study of the autonomic
      regulation during sleep allowed developing methods for automatic detection and
      classification of some sleep characteristics, both in physiological and
      pathological conditions. The main problems which require to be faced are the
      presence of frequent non-stationarities in the signal and the need of dealing
      with long term analysis, in order to provide reliable indices able to describe
      the whole night of sleep. In the present paper we are presenting some of the
      methodologies we recently employed in the study of the heart rate variability
      during sleep, ranging from time-frequency analysis to long time correlation. Some
      results are also presented, related to different applications, dealing with both
      physiological and pathological conditions. 

PMID- 24111251
TI  - Capacity of small groups of muscles to accomplish precision grasping tasks.
AB  - An understanding of the capacity or ability of various muscle groups to generate
      endpoint forces that enable grasping tasks could provide a stronger biomechanical
      basis for the design of reconstructive surgery or rehabilitation for the
      treatment of the paralyzed or paretic hand. We quantified two-dimensional
      endpoint force distributions for every combination of the muscles of the index
      finger, in cadaveric specimens, to understand the capability of muscle groups to
      produce endpoint forces that accomplish three common types of grasps-tripod, tip
      and lateral pinch-characterized by a representative level of Coulomb friction. We
      found that muscle groups of 4 or fewer muscles were capable of generating
      endpoint forces that enabled performance of each of the grasping tasks examined.
      We also found that flexor muscles were crucial to accomplish tripod pinch;
      intrinsic muscles, tip pinch; and the dorsal interosseus muscle, lateral pinch.
      The results of this study provide a basis for decision making in the design of
      reconstructive surgeries and rehabilitation approaches that attempt to restore
      the ability to perform grasping tasks with small groups of muscles. 

PMID- 24111252
TI  - A novel experimental method to evaluate motor task control in Parkinson's
      patients.
AB  - In this paper, a novel experimental method was developed to study planar arm
      movement control in tremor dominant Parkinson's (PD) patients. The method
      utilized a ball-bearing supported fiberglass brace apparatus against gravity to
      maintain the upper extremity in the horizontal plane. Subjects can perform
      postural and movement tasks with minimum damping effects. Arm movements were
      recorded using the MotionMonitor II system concurrently with EMGs of multiple
      muscles. Testing results in normal subjects with and without the brace support
      showed that the inertia and damping effects were negligible for oscillatory arm
      movement at maximum voluntary frequency (MVF). The tremor behaviors in horizontal
      posture maintenance and reaching movement in three PD subjects were also obtained
      with this method. The average frequency of postural tremor was 4.34 +/- 0.15 Hz
      in all arm positions tested. However, the tremor magnitudes changed significantly
      with posture locations. In performing reaching movements, the tremor was
      inhibited prior to reaching, but resumed after reaching. These results may
      provide interesting insights into the pathological mechanisms of Parkinsonian
      tremor, as well as the modular nature of neural control of movements.

PMID- 24111253
TI  - A portable system for quantitative assessment of parkinsonian rigidity.
AB  - Rigidity is one of the primary symptoms of Parkinson's disease. Passive flexion
      and extension of the elbow is used to assess rigidity in this study. An examiner
      flexes and extends the subject's elbow joint through a rigidity assessment cuff
      attached around the wrist. Each assessment lasts for 10 seconds. Two force sensor
      boxes and an inertial measurement unit are used to measure the applied force and
      the state of the elbow movement. Elastic and viscous values will be obtained
      through a least squares estimation with all the data. 9 healthy subjects were
      tested with this system in two experimental conditions: 1) normal state
      (relaxed); 2) imitated rigidity state. Also the subjects were performed the
      assessment task with different frequencies and elbow movement ranges. The
      imitated rigidity action increases viscosity and elasticity. The effect sizes
      (Cohen's d) of the viscosity and elasticity between normal state and imitated
      state are 1.61 and 1.36 respectively, which means the difference is significant.
      Thus, this system can detect the on-off fluctuations of parkinsonian rigidity.
      Both wrist movement angle and frequency have small effect on the viscosity, but
      have elevated effect on the elasticity. 

PMID- 24111254
TI  - The role of delta-modulated high frequency oscillations in seizure state
      classification.
AB  - High frequency oscillations (HFOs), which collectively refer to ripples (80-200
      Hz) and fast ripples (>200 Hz), have been implicated as key players in
      epileptogenesis. However, their presence alone is not in and of itself indicative
      of a pathological brain state. Rather, spatial origins as well as coexistence
      with other neural rhythms are essential components in defining pathological HFOs.
      This study investigates how the phase of the delta rhythm (0.5-4 Hz) modulates
      the amplitude of HFOs during a seizure episode. Seven seizures recorded from
      three patients presenting with intractable temporal lobe epilepsy were obtained
      via intracranial electroencephalography (iEEG) from a 64-electrode grid. Delta
      modulation of the HFO rhythms was found to emerge at seizure onset and
      termination regardless of the dynamics present within the seizure episode itself.
      Moreover, the differences between delta modulating the ripple or fast ripple may
      be due to the sleep stage of the patient when the seizures were being recorded.
      Further studies exploring how this modulation changes in space across the grid
      may also highlight additional properties of this phenomenon. Its temporal pattern
      suggests that it is a potential iEEG-based biomarker for seizure state
      classification. 

PMID- 24111255
TI  - Restored brain perfusion after non-invasive stimulation of the facial nerve in a
      canine stroke model.
AB  - Ischemic stroke affects over 15 million patients per year and is a leading cause
      of death worldwide. Currently available treatments are indicated for less than 5%
      of patients. Stimulation of the facial nerve has been proposed as a possible new
      treatment of ischemic stroke that acts by increasing blood flow to the brain and
      thereby restoring perfusion through collateral vessels. The objective of this
      project was to evaluate the changes in brain perfusion, following facial nerve
      stimulation in an animal stroke model using MRI measures of cerebral blood flow.
      Autologous blood clot was injected in the internal carotid artery to occlude the
      middle cerebral artery (MCA) in 17 mongrel dogs. Occlusion in the MCA was
      verified using fluoroscopy and MRI angiography. Following baseline and post
      stroke MRI images, the facial nerve at the site of the geniculate ganglion was
      located and then stimulated using a transcranial magnetic stimulator and a neuro
      navigation system in 11 animals. Six animals followed the same procedure but were
      not stimulated (control group). The perfusion index of both sides of the brain
      was measured using gadolinium contrast MRI before and after stroke, and at 30
      minute intervals after stimulation. Results show a significant and persistent
      increase in perfusion in the stroke side of the brain relative to the non-stroke
      / contralateral side, after stimulation, when compared to the control group.
      These results strongly support the future development and evaluation of a non
      invasive facial nerve stimulator device for the early treatment of ischemic
      stroke. 

PMID- 24111256
TI  - A clinical study of motor imagery BCI performance in stroke by including
      calibration data from passive movement.
AB  - Electroencephalogram (EEG) data from performing motor imagery are usually used to
      calibrate a subject-specific model in Motor Imagery Brain-Computer Interface (MI
      BCI). However, the performance of MI is not directly observable by another
      person. Studies that attempted to address this issue in order to improve subjects
      with low MI performance had shown that it is feasible to use calibration data
      from Passive Movement (PM) to detect MI in healthy subjects. This study
      investigates the feasibility of using calibration data from PM of stroke patients
      to detect MI. EEG data from 2 calibration runs of MI and PM by a robotic haptic
      knob, and 1 evaluation run of MI were collected in one session of recording from
      34 hemiparetic stroke patients recruited in the clinical study. In each run, 40
      trials of MI or PM and 40 trials of the background rest were collected. The off
      line run-to-run transfer kappa values from the calibration runs of MI, PM, and
      combined MI and PM, to the evaluation run of MI were then evaluated and compared.
      The results showed that calibration using PM (0.392) yielded significantly lower
      kappa value than the calibration using MI (0.457, p=4.40e-14). The results may be
      due to a significant disparity between the EEG data from PM and MI in stroke
      subjects. Nevertheless, the results showed that the calibration using both MI and
      PM (0.506) yielded significantly higher kappa value than the calibration using MI
      (0.457, p=9.54e-14). Hence, the results of this study suggest a promising
      direction to combine calibration data from PM and MI to improve MI detection on
      stroke. 

PMID- 24111257
TI  - Mental fatigue and working memory load estimation: interaction and implications
      for EEG-based passive BCI.
AB  - Current mental state monitoring systems, a.k.a. passive brain-computer interfaces
      (pBCI), allow one to perform a real-time assessment of an operator's cognitive
      state. In EEG-based systems, typical measurements for workload level assessment
      are band power estimates in several frequency bands. Mental fatigue, arising from
      growing time-on-task (TOT), can significantly affect the distribution of these
      band power features. However, the impact of mental fatigue on workload (WKL)
      assessment has not yet been evaluated. With this paper we intend to help fill in
      this lack of knowledge by analyzing the influence of WKL and TOT on EEG band
      power features, as well as their interaction and its impact on classification
      performance. Twenty participants underwent an experiment that modulated both
      their WKL (low/high) and time spent on the task (short/long). Statistical
      analyses were performed on the EEG signals, behavioral and subjective data. They
      revealed opposite changes in alpha power distribution between WKL and TOT
      conditions, as well as a decrease in WKL level discriminability with increasing
      TOT in both number of statistical differences in band power and classification
      performance. Implications for pBCI systems and experimental protocol design are
      discussed. 

PMID- 24111258
TI  - Probing ECG-based mental state monitoring on short time segments.
AB  - Electrocardiography is used to provide features for mental state monitoring
      systems. There is a need for quick mental state assessment in some applications
      such as attentive user interfaces. We analyzed how heart rate and heart rate
      variability features are influenced by working memory load (WKL) and time-on-task
      (TOT) on very short time segments (5s) with both statistical significance and
      classification performance results. It is shown that classification of such
      mental states can be performed on very short time segments and that heart rate is
      more predictive of TOT level than heart rate variability. However, both features
      are efficient for WKL level classification. What's more, interesting interaction
      effects are uncovered: TOT influences WKL level classification either favorably
      when based on HR, or adversely when based on HRV. Implications for mental state
      monitoring are discussed. 

PMID- 24111259
TI  - A wearable device for measuring eye dynamics in real-world conditions.
AB  - Drowsiness and lapses of responsiveness have the potential to cause fatalities in
      many occupations. One subsystem of a prototype device which aims to detect these
      lapses as they occur is described. A head-mounted camera measures several
      features of the eye that are known to correlate with drowsiness. The system was
      tested with eight combinations of eye colour, ambient lighting, and eye glasses
      to simulate typical real-world input conditions. A task was completed for each
      set of conditions to simulate a range of eye movement-saccades, tracking, and eye
      closure. Our image processing software correctly classified 99.3% of video frames
      as open/closed/partly closed, and the error rate was not affected by the
      combinations of input conditions. Most errors occurred during eyelid movement.
      The accuracy of the pupil localisation was also not influenced by input
      conditions, with the possible exception of one subject's glasses.

PMID- 24111260
TI  - Frontal EEG theta changes assess the training improvements of novices in flight
      simulation tasks.
AB  - The aim of the study is to analyze the variation of the EEG power spectra in
      theta band when a novice starts to learn a new task. In particular, the goal is
      to find out the differences from the beginning of the training to the session in
      which the performance level is good enough for considering him/her able to
      complete the task without any problems. While the novices were engaged in the
      flight simulation tasks we recorded the brain activity by using high resolution
      EEG techniques as well as neurophysiologic variables such as heart rate (HR) and
      eye blinks rate (EBR). Results show clear changes in the EEG power spectra in
      theta band over the frontal brain areas, either over the left, the midline and
      the right side, during the learning process of the task. These results are also
      supported by the autonomic signals of HR and EBR, by the performances' trends and
      by the questionnaires for the evaluation of the perceived workload level. 

PMID- 24111261
TI  - A robust principal component analysis algorithm for EEG-based vigilance
      estimation.
AB  - Feature dimensionality reduction methods with robustness have a great
      significance for making better use of EEG data, since EEG features are usually
      high-dimensional and contain a lot of noise. In this paper, a robust principal
      component analysis (PCA) algorithm is introduced to reduce the dimension of EEG
      features for vigilance estimation. The performance is compared with that of
      standard PCA, L1-norm PCA, sparse PCA, and robust PCA in feature dimension
      reduction on an EEG data set of twenty-three subjects. To evaluate the
      performance of these algorithms, smoothed differential entropy features are used
      as the vigilance related EEG features. Experimental results demonstrate that the
      robustness and performance of robust PCA are better than other algorithms for
      both off-line and on-line vigilance estimation. The average RMSE (root mean
      square errors) of vigilance estimation was 0.158 when robust PCA was applied to
      reduce the dimensionality of features, while the average RMSE was 0.172 when
      standard PCA was used in the same task. 

PMID- 24111262
TI  - Differential entropy feature for EEG-based vigilance estimation.
AB  - This paper proposes a novel feature called differential entropy for EEG-based
      vigilance estimation. By mathematical derivation, we find an interesting
      relationship between the proposed differential entropy and the existing logarithm
      energy spectrum. We present a physical interpretation of the logarithm energy
      spectrum which is widely used in EEG signal analysis. To evaluate the performance
      of the proposed differential entropy feature for vigilance estimation, we compare
      it with four existing features on an EEG data set of twenty-three subjects. All
      of the features are projected to the same dimension by principal component
      analysis algorithm. Experiment results show that differential entropy is the most
      accurate and stable EEG feature to reflect the vigilance changes. 

PMID- 24111263
TI  - Neuromuscular interfacing: a novel approach to EMG-driven multiple DOF
      physiological models.
AB  - This paper presents a novel approach that involves first identifying and
      verifying the available superficial muscles that can be recorded by surface
      electromyography (EMG) signals, and then developing a musculoskeletal model based
      on these findings, which have specifically independent DOFs for movement. Such
      independently controlled multiple DOF EMG-driven models have not been previously
      developed and a two DOF model for the masticatory system was achieved by
      implementing independent antagonist muscle combinations for vertical and lateral
      movements of the jaw. The model has six channels of EMG signals from the
      bilateral temporalis, masseter and digastric muscles to predict the motion of the
      mandible. This can be used in a neuromuscular interface to manipulate a jaw
      exoskeleton for rehabilitation. For a range of different complexities of jaw
      movements, the presented model is able to consistently identify movements with
      0.28 - 0.46 average normalized RMSE. The results demonstrate the feasibility of
      the approach at determining complex multiple DOF movements and its applicability
      to any joint system. 

PMID- 24111264
TI  - A pilot study of high-density electromyographic maps of muscle activity in normal
      deglutition.
AB  - While various methods have been used to study physiological aspects of
      swallowing, few studies have been conducted to investigate the dynamics of a
      swallowing procedure with the activation pattern of swallowing muscles. In this
      pilot study we investigated the feasibility of surface electromyographic (sEMG)
      dynamic topography as a new approach for continuously visualizing muscle activity
      of normal swallowing. The dynamic sEMG topographies (or potential mappings) of
      swallowing were constructed with high-density sEMG recordings from three subjects
      without any swallowing disorders. The root mean square (RMS) of the sEMG signals
      was calculated as a function of both position and time to produce two-dimension
      dynamic sEMG maps of the muscle activity during swallowing. The sEMG maps could
      provide the information about the dynamic characteristics of swallowing muscles,
      which is accordance with physiological and biomechanical laws of a normal
      swallowing. With the results of the present study, we might conclude that the
      dynamic topography would provide a noninvasive means to continuously visualize
      the distribution of surface EMG signals of complex muscle activities of normal
      deglutition. 

PMID- 24111265
TI  - Inverse estimation of muscle activations from joint torque via local multiple
      regression.
AB  - The signal measured with an electromyogram (EMG) is the summation of all action
      potentials of motor units active at a certain time. According to previous
      literature, one can establish the relationship between torque and EMG/activations
      in a forward way, i.e., employing EMG of multiple channels to estimate the joint
      torque. Once the relationship is established, the torque can be predicted with
      EMG recordings. However, in some applications of neuroprosthetics where we need
      to make muscle control, it is required to inversely have an insight regarding the
      muscle activations under a specific motion scenario from the corresponding
      torque. Motivated by this point, this paper investigates inverse estimation of
      muscle activations in random contractions at the ankle joint. Local multiple
      regression is exploited for finding the relationship between muscle activations
      and torque. Such technique is able to rebuild the relationship between muscle
      activations and joint torque inversely based on experimental data obtained from
      five able-bodied subjects, and the resultant optimal weight matrix can indicate
      each muscle's contribution in the production of the torque. Further cross
      validation on prediction of muscle activations with joint torque with optimal
      weights shows that such approach may possess promising performance. 

PMID- 24111266
TI  - Study on sEMG-based exercise therapy for upper limb of severe hemiplegic
      patients.
AB  - sEMG, as a kind of bioelectrical signal reflecting muscle motion state, generally
      applies to motion recognition and human interface. Healthy subjects are selected
      in most studies, while for hemiplegic patients, especially patients with severe
      hemiplegia, high accuracy motion recognition is difficult to acquire due to the
      non-ideal sEMG signal from dysfunction muscles. Therefore, this paper presents an
      upper limb exercise therapy, based on 5 defined motions and 6 Muscle-Units, for
      patients with severe hemiplegia. Through the sampling and analysis of sEMG
      signals from 8 subjects, including 4 healthy and 4 hemiplegic patients, we draw a
      conclusion of the relevance between specific motions and Muscle-Units, which can
      be used as a reference for paralyzed arm training. According to this relevance,
      six Muscle-Units can be classified into two categories: major Muscle-Units and
      minor Muscle-Units. In order to improve the interest and positivity of patients,
      a PC based virtual interactive platform is established. The sEMG signal from
      major Muscle-Units is processed with a moving average algorithm, and the result
      is used as the control signal for training interaction. 

PMID- 24111267
TI  - SEMG pattern classification using hierarchical Bayesian model.
AB  - This work addresses surface electromyogram (sEMG)-based muscle pattern
      classification using a generative model. By using a hierarchical Bayesian model,
      the proposed approach constructs an overall process model of recorded sEMG
      signals. By inferring probabilistically latent neural states which governs a
      collection of training sEMG data, classification is realized. To validate the
      approach, eight-class classification using four sEMG sensors on the limb actions
      is tested with five subjects. The proposed model achieves an overall 95% accuracy
      in the classification experiment. The results support that the proposed approach
      is very promising for sEMG pattern classification. 

PMID- 24111268
TI  - Evaluation of classifier topologies for the real-time classification of
      simultaneous limb motions.
AB  - The prediction of motion intent through the decoding of myoelectric signals has
      the potential to improve the functionally of limb prostheses. Considerable
      research on individual motion classifiers has been done to exploit this idea. A
      drawback with the individual prediction approach, however, is its limitation to
      serial control, which is slow, cumbersome, and unnatural. In this work, different
      classifier topologies suitable for the decoding of mixed classes, and thus
      capable of predicting simultaneous motions, were investigated in real-time. These
      topologies resulted in higher offline accuracies than previously achieved, but
      more importantly, positive indications of their suitability for real-time systems
      were found. Furthermore, in order to facilitate further development,
      benchmarking, and cooperation, the algorithms and data generated in this study
      are freely available as part of BioPatRec, an open source framework for the
      development of advanced prosthetic control strategies. 

PMID- 24111269
TI  - Fabrication of perfusable vasculatures by using micromolding and electrochemical
      cell transfer.
AB  - Fabrication of vascular networks for the delivery of oxygen and nutrients is a
      critical issue when engineering 3-dimensional tissues and organs. This study
      describes an approach that involves micromolding and electrochemical cell
      transfer and can be employed to fabricate endothelial cell-lined vascular-like
      structures that are precisely aligned at micrometer intervals in a
      photocrosslinkable gelatin hydrogel. Subsequent perfusion culture induces the
      migration and sprouting of endothelial cells in the hydrogel and facilitates
      luminal structure formation. 

PMID- 24111270
TI  - Fabrication of polymeric microfluidic devices with tunable wetting behavior for
      biomedical applications.
AB  - We demonstrate the fabrication of microchannels with specific fluidic behavior
      due to micro- and/or nanostructures on the surfaces. With a combination of hot
      embossing and microthermoforming it is possible to produce microchannels with
      specific surface properties. These surface properties are highly dependent on the
      micro- and nanostructures embossed into the material. Different structure sizes
      and geometries where examined by contact angle measurements. Here the dependency
      of diameter and pitch of the structures on the contact angle is examined as well
      as the material impact. These results enable the fabrication of highly specific
      surfaces tunable to an application. 

PMID- 24111271
TI  - Micropatterning C2C12 myotubes for orderly recording of intracellular calcium
      transients.
AB  - Reconstruction of skeletal muscle myotubes in vitro using myogenic cell lines
      have been widely carried out to study functional properties and disease-related
      biological changes of myotubes, such as intracellular calcium dynamics. However,
      the analysis of biological signals in isolated single myotubes or interactions
      among several myotubes is quite difficult problem because of the randomness in
      size, morphology and orientation of differentiated myotubes cultured on a
      conventional tissue culture dish. In the present study, we attempted to form
      uniform-size myotubes and detect intracellular calcium dynamics from the
      fabricated myotubes. We modified surfaces of culture dishes using a poly(
      dimethylsiloxane) (PDMS) stamp and a 2-methacryloyloxyethyl phosphorylcholine
      (MPC) polymer solution to form line patterns for myotube formation. We could form
      uniform-size and -orientation C2C12 myotubes and detect intracellular calcium
      dynamics from it. This simple method would be a useful for studying properties in
      myotubes with specific sizes and morphologies. 

PMID- 24111272
TI  - Preparation and evaluation of collagen I/ gellan gum/beta-TCP microspheres as
      bone graft substitute materials.
AB  - Collagen I is the main component of protein in bone and exhibits many excellent
      applications in biomedical fields. Gellan gum possesses good biocompatible,
      biodegradable and good mechanical property, and shows great potentials as tissue
      engineering scaffold or cell culture substrate. Therefore, the aim of this study
      was to use collagen I, gellan gum and beta-TCP to prepare collagen I/gellan
      gum/beta-TCP microspheres by emulsion method as bone graft substitute materials.
      The preliminary results showed that collagen I/gellan gum/beta-TCP microspheres
      had particle size distribution between 500-1000 uP in diameter and exhibited
      better mechanical strength. These microspheres also showed good biocompatibility
      in cell activity test. 

PMID- 24111273
TI  - Gelatin nanofiber-reinforced alginate gel scaffolds for corneal tissue
      engineering.
AB  - A severe shortage of donor cornea is now an international crisis in public
      health. Substitutes for donor tissue need to be developed to meet the increasing
      demand for corneal transplantation. Current attempts in designing scaffolds for
      corneal tissue regeneration involve utilization of expensive materials. Yet,
      these corneal scaffolds still lack the highly-organized fibrous structure that
      functions as a load-bearing component in the native tissue. This work shows that
      transparent nanofiber-reinforced hydrogels could be developed from cheap, non
      immunogenic and readily available natural polymers to mimic the cornea's
      microstructure. Electrospinning was employed to produce gelatin nanofibers, which
      were then infiltrated with alginate hydrogels. Introducing electrospun nanofibers
      into hydrogels improved their mechanical properties by nearly one order of
      magnitude, yielding mechanically robust composites. Such nanofiber-reinforced
      hydrogels could serve as alternatives to donor tissue for corneal
      transplantation. 

PMID- 24111274
TI  - Bidirectional synaptic connection between primary and stem cell-derived neurons
      in co-culture device.
AB  - Regenerative medicine is expected to be a potent therapeutic option for the
      disorders or injuries of the central nervous system. However, little is known
      about how the newly formed neurons derived from grafted stem cells integrate into
      the host established tissue. The aims of this study are to make functional
      connection between primary neurons and stem cell-derived neurons via chemical
      synapses and maintain the connection for a long time in in vitro. We employed an
      in vitro co-culture device to cultivate two different neuronal populations and
      evaluate the interaction between them. Mouse cortical neurons and P19 cell
      derived neurons were co-cultured in the co-culture device. The synchronous
      activities were maintained for at least 4 weeks. Evoked responses to electrical
      stimulation suggested that bi-directional connections were formed between
      cortical and P19-derived neurons. The responses were changed after
      pharmacological treatment. These results showed that cortical neurons and P19
      cell-derived neurons formed bidirectional synaptic connections via glutamate
      receptors and the connection was maintained for at least 4 weeks. 

PMID- 24111275
TI  - Upper-limb tremor suppression with a 7DOF exoskeleton power-assist robot.
AB  - A tremor which is one of the involuntary motions is somewhat rhythmic motion that
      may occur in various body parts. Although there are several kinds of the tremor,
      an essential tremor is the most common tremor disorder of the arm. The essential
      tremor is a disorder of unknown cause, and it is common in the elderly. The
      essential tremor interferes with a patient's daily living activity, because it
      may occur during a voluntary motion. If a patient of an essential tremor uses an
      EMG-based controlled power-assist robot, the robot might misunderstand the user's
      motion intention because of the effect of the essential tremor. In that case,
      upper-limb power-assist robots must carry out tremor suppression as well as power
      assist, since a person performs various precise tasks with certain tools by the
      upper-limb in daily living. Therefore, it is important to suppress the tremor at
      the hand and grasped tool. However, in the case of the tremor suppression control
      method which suppressed the vibrations of the hand and the tip of the tool,
      vibration of other part such as elbow might occur. In this paper, the tremor
      suppression control method for upper-limb power-assist robot is proposed. In the
      proposed method, the vibration of the elbow is suppressed in addition to the hand
      and the tip of the tool. The validity of the proposed method was verified by the
      experiments. 

PMID- 24111276
TI  - Coaxial needle insertion assistant for epidural puncture effect of lateral force
      on needle.
AB  - We validated the effectiveness of a coaxial needle insertion assistant under the
      condition that the needles were laterally deformed. The coaxial needle insertion
      assistant separates the cutting force at the needle tip from shear friction on
      the needle shaft, and haptically display it to a user in order to assists her/his
      perception during epidural puncture. An outer needle covers the side of an inner
      needle, preventing the shear friction from acting on the inner needle. However
      when the needles are laterally deformed and make contact to each other, it is
      concerned that the effect of the separation is degraded. In this paper, the users
      punctured an artificial tissue with variable insertion angles, so that the needle
      is intentionally laterally deformed. The overshoot and user confidence in
      detecting puncture was examined. 

PMID- 24111277
TI  - An implantable neural activity monitor with nonlinear gain-controlled amplifier.
AB  - An implantable neural spike monitor with nonlinear amplifier was proposed for
      robust measurement against noise. In embedded electrophysiological signal
      processing systems, detection performance depends on signal to noise ratio (SNR),
      however, it is getting worth after implantation because of neoformation
      surrounding the electrodes and so on. We proposed a spike enhancer in this study.
      It has two remarkable function; automatic gain optimization with feedback loop
      and SNR improvement by nonlinear amplifier. In this report, the system
      performance was evaluated without feedback loop. A prototype circuit is prepared
      with small number of parts and tested on input-output characteristics. For the
      final evaluation, neural spike signal from somatosensory cortex of a rat was
      applied to the circuit. The test results show that system can expand SNR on
      neural spike signal from rat. It indicates that the spike enhancer can improve
      total performance of neural activity processing system. 

PMID- 24111278
TI  - Histological observation for needle-tissue interactions.
AB  - We histologically investigated tissue fractures and deformations caused by ex
      vivo needle insertions. The tissue was formalin-fixed while the needle remained
      in the tissue. Following removal of the needle, the tissue was microtomed,
      stained, and observed microscopically. This method enabled observations of
      cellular and tissular conditions where deformations caused by needle insertions
      were approximately preserved. For this study, our novel method presents
      preliminary findings related with tissue fractures and the orientation of needle
      blade relative to muscle fibers. When the needle blade was perpendicular to the
      muscle fiber, transfiber fractures and relatively large longitudinal deformations
      occurred. When the needle blade was parallel to the muscle fiber, interfiber
      fractures and relatively small longitudinal deformations occurred. This made a
      significant difference in the resistance force of the needle insertions. 

PMID- 24111279
TI  - Robotic tensor device for optimal soft tissue balance in TKA.
AB  - Soft tissue balance measurement is necessary for effective total knee
      arthroplasty (TKA). If optimal ligament balance is not achieved during surgery,
      it results in laxity of the knee or repeat surgery. In this paper, a newly
      developed robotic tensor system for measurement of soft tissue balance during TKA
      is described. The development concepts of the system were to measure collateral
      ligament balance (joint gap distance and varus angle) after cutting of the tibia
      and femur and to generate arbitrary lifting force to the knee joint during
      surgery. The system was created according to the development concepts. The
      prototype system has an active prismatic joint and a passive rotation joint to
      assess the joint gap and varus angle. The maximum lifting force is 250 N, the
      measurement range of the joint gap is 30 mm, and the varus angle is +/- 15
      degrees . To confirm the force control ability, a basic experiment was performed.
      The input target force was 100, 150, 200, 250 N, and the output result showed an
      error within 3N. This experimental result shows that the newly developed system
      appears to have better accuracy than previous instrumental methods.

PMID- 24111280
TI  - Biomechanical analysis for the epidural needle insertion.
AB  - In order to test the hypothesis about reduction in the deformation of the
      ligamentum flavum due to tension inside the ligamentum flavum, nonlinear finite
      element (FE) analysis was employed. As a preliminary analysis of natural tissue,
      nonlinear FE analysis was applied to a rubber plate. Assuming that the rubber is
      third-order Mooney-Rivlin model, the analysis and the experimental curves overlap
      with each other until pierced point. The maximum major strain calculated by FE
      analysis was feasible to predict pierced point. To apply nonlinear FE analysis
      for the porcine ligamentum flavum, the Mooney-Rivlin coefficient of the porcine
      ligamentum flavum was identified from the tensile test data. Assuming that the
      sharp bar pierced the ligamentum flavum when the maximum major strain reached a
      constant value, the required displacement became shorter by 1.0mm by applying the
      initial tension. 

PMID- 24111281
TI  - Motor recovery monitoring in post acute stroke patients using wireless
      accelerometer and cross-correlation.
AB  - Stroke is a major reason for physical immobility and death. For effective
      treatment of stroke, early diagnosis and aggressive medication in the form of
      thrombolytic drugs is shown to be essential. In order to provide proper care, the
      patient should be kept under continuous monitoring during the first few hours
      after subjecting thrombolytic drugs and based on the response of the patient to
      the medication, line of treatment should be changed. In our previous work [1], we
      have shown the proof of principle by monitoring the motor activity of the stroke
      patient using accelerometer fitted on patient's arms. Based on preliminary
      analysis, we proposed methods using resultant acceleration signal and showed its
      effectiveness in predicting National Institute of Health Stroke Scale (NIHSS)
      stroke index. In this paper, novel technique based on cross-correlation of
      accelerometer values along different axes is developed for predicting the NIHSS
      index. An overall increase in prediction accuracy by over 7% compared to the
      earlier method is obtained. A multi-class support vector machine (SVM) classifier
      for cross correlation features is also designed and an overall prediction
      accuracy of 93% is achieved. 

PMID- 24111282
TI  - Estimation of removed uremic toxin indoxyl sulphate during hemodialysis by using
      optical data of the spent dialysate.
AB  - The aim of this study was to explore the possibility to determine the amount of
      total removed Indoxyl Sulphate (TR_IS) during dialysis session, an optical method
      utilizing absorbance and fluorescence spectral data of the spent dialysate was
      used. Eight uremic patients from Linkoping, Sweden and 10 from Tallinn, Estonia,
      were studied during dialysis treatments. Dialysate samples were taken during each
      treatment and analyzed at a laboratory. Fluorescence and absorbance spectra of
      the spent dialysate were measured with spectrofluorophotometer and
      spectrophotometer. The spectral values were transformed into IS concentration
      using multiple linear regression model from the total material noted as optical
      method (Opt). IS concentration was estimated using high-performance liquid
      chromatography (HPLC) method as a reference. TR_IS values were calculated.
      Achieved results were compared regarding mean values and SD and collated with the
      amount of total removed urea value (TR_Urea) for the same dialysis procedures.
      Mean TR value +/- SD (mg) for urea was 28 947 +/- 9 241; TR for IS was 151.4 +/-
      87.3 estimated by HPLC and 149.4 +/- 84.9 estimated by Opt. The TR_IS values were
      not significantly different (p <= 0.05). This study indicates, that it is
      possible to estimate TR_IS using only spectral values of the spent dialysate and
      the parameter can be used for quantifying the elimination of protein bound uremic
      toxins during the dialysis procedure.

PMID- 24111283
TI  - Demonstrating the accuracy of an in-hospital ambulatory patient monitoring
      solution in measuring respiratory rate.
AB  - This paper presents clinical testing conducted to evaluate the accuracy of
      Aingeal, a wireless in-hospital patient monitor, in measuring respiration rate
      via impedance pneumography. Healthy volunteers were invited to simultaneously
      wear a CE Marked Aingeal vital signs monitor and a capnograph, the current gold
      standard in respiration rate measurement. During the test, participants were
      asked to undergo a series of defined breathing protocols which included normal
      breathing, paced breathing between 8-23 breaths per minute (bpm) and a recovery
      period following moderate exercise. Statistical analysis of the data collected
      shows a mean difference of -0.73, a standard deviation of 1.61, limits of
      agreement of -3.88 and +2.42 bpm and a P-value of 0.22. This testing demonstrates
      comparable performance of the Aingeal device in measuring respiration rate with a
      well-accepted and widely used alternative method. 

PMID- 24111284
TI  - Development of an infection screening system for entry inspection at airport
      quarantine stations using ear temperature, heart and respiration rates.
AB  - After the outbreak of severe acute respiratory syndrome (SARS) in 2003, many
      international airport quarantine stations conducted fever-based screening to
      identify infected passengers using infrared thermography for preventing global
      pandemics. Due to environmental factors affecting measurement of facial skin
      temperature with thermography, some previous studies revealed the limits of
      authenticity in detecting infectious symptoms. In order to implement more strict
      entry screening in the epidemic seasons of emerging infectious diseases, we
      developed an infection screening system for airport quarantines using multi
      parameter vital signs. This system can automatically detect infected individuals
      within several tens of seconds by a neural-network-based discriminant function
      using measured vital signs, i.e., heart rate obtained by a reflective photo
      sensor, respiration rate determined by a 10-GHz non-contact respiration radar,
      and the ear temperature monitored by a thermography. In this paper, to reduce the
      environmental effects on thermography measurement, we adopted the ear temperature
      as a new screening indicator instead of facial skin. We tested the system on 13
      influenza patients and 33 normal subjects. The sensitivity of the infection
      screening system in detecting influenza were 92.3%, which was higher than the
      sensitivity reported in our previous paper (88.0%) with average facial skin
      temperature. 

PMID- 24111285
TI  - A new ecological method for the estimation of Nutritive Sucking Efficiency in
      newborns: measurement principle and experimental assessment.
AB  - The Sucking Efficiency (SEF) is one of the main parameters used to monitor and
      assess the sucking pattern development in infants. Since Nutritive Sucking (NS)
      is one of the earliest motor activity performed by infants, its objective
      monitoring may allow to assess neurological and motor development of newborns.
      This work proposes a new ecological and low-cost method for SEF monitoring,
      specifically designed for feeding bottles. The methodology, based on the measure
      of the hydrostatic pressure exerted by the liquid at the teat base, is presented
      and experimentally validated at different operative conditions. Results show how
      the proposed method allows to estimate the minimum volume an infant ingests
      during a burst of sucks with a relative error within the range of [3-7]%
      depending on the inclination of the liquid reservoir

PMID- 24111286
TI  - Novel screen printed electrode set for routine EEG recordings in patients with
      altered mental status.
AB  - There is a growing need for an easy to use screening tool for the assessment of
      brain's electrical function in patients with altered mental status (AMS). The
      purpose of this study is to give a brief overview of the state-of-the-art in
      electrode technology, and to present a novel sub-hairline electrode set developed
      in our research group. Screen-printing technology was utilized to construct the
      electrode set consisting of ten electroencephalography (EEG) electrodes, two
      electrooculography (EOG) electrodes, two ground electrodes and two reference
      electrodes. Electrical characteristics of hydrogel-coated silver ink electrodes
      were found adequate for clinical EEG recordings as assessed by electrical
      impedance spectroscopy (EIS). The skin-electrode impedances remain stable and low
      enough at least two days enabling high-quality long-term recordings. Due to the
      proper material selection, thin ink layers and detachable zero insertion force
      (ZIF) - connector, electrode was observed to be CT- and MRI-compatible allowing
      imaging without removing the electrodes. Pilot EEG recordings gave very promising
      results and an on-going clinical trial with larger number of patients will show
      the true feasibility of this approach. 

PMID- 24111287
TI  - A hybrid localization technique for patient tracking.
AB  - Nowadays numerous technologies are employed for tracking patients and assets in
      hospitals or nursing homes. Each of them has advantages and drawbacks. For
      example, WiFi localization has relatively good accuracy but cannot be used in
      case of power outage or in the areas with poor WiFi coverage. Magnetometer
      positioning or cellular network does not have such problems but they are not as
      accurate as localization with WiFi. This paper describes technique that
      simultaneously employs different localization technologies for enhancing
      stability and average accuracy of localization. The proposed algorithm is based
      on fingerprinting method paired with data fusion and prediction algorithms for
      estimating the object location. The core idea of the algorithm is technology
      fusion using error estimation methods. For testing accuracy and performance of
      the algorithm testing simulation environment has been implemented. Significant
      accuracy improvement was showed in practical scenarios. 

PMID- 24111288
TI  - Biosignal-based relaxation evaluation of head-care robot.
AB  - Such popular head care procedures as shampooing and scalp massages provide
      physical and mental relaxation. However, they place a big burden such as chapped
      hands on beauticians and other practitioners. Based on our robot hand technology,
      we have been developing a head care robot. In this paper, we quantitatively
      evaluated its relaxation effect using the following biosignals: accelerated
      plethymography (SDNN, HF/TP, LF/HF), heart rate (HR), blood pressure, salivary
      amylase (sAA) and peripheral skin temperature (PST). We compared the relaxation
      of our developed head care robot with the head care provided by nurses. In our
      experimental result with 54 subjects, the activity of the autonomic nerve system
      changed before and after head care procedures performed by both a human nurse and
      our proposed robot. Especially, in the proposed robot, we confirmed significant
      differences with the procedure performed by our proposed head care robot in five
      indexes: HF/TP, LF/HF, HR, sAA, and PST. The activity of the sympathetic nerve
      system decreased, because the values of its indexes significantly decreased:
      LF/HF, HR, and sAA. On the other hand, the activity of the parasympathetic nerve
      system increased, because of the increase of its indexes value: HF/TP and PST.
      Our developed head care robot provided satisfactory relaxation in just five
      minutes of use. 

PMID- 24111289
TI  - Improvement of acoustic fall detection using Kinect depth sensing.
AB  - The latest acoustic fall detection system (acoustic FADE) has achieved
      encouraging results on real-world dataset. However, the acoustic FADE device is
      difficult to be deployed in real environment due to its large size. In addition,
      the estimation accuracy of sound source localization (SSL) and direction of
      arrival (DOA) becomes much lower in multi-interference environment, which will
      potentially result in the distortion of the source signal using beamforming (BF).
      Microsoft Kinect is used in this paper to address these issues by measuring
      source position using the depth sensor. We employ robust minimum variance
      distortionless response (MVDR) adaptive BF (ABF) to take advantage of well
      estimated source position for acoustic FADE. A significant reduction of false
      alarms and improvement of detection rate are both achieved using the proposed
      fusion strategy on real-world data. 

PMID- 24111290
TI  - Signal phase estimation for measurement of respiration waveform using a microwave
      Doppler sensor.
AB  - This paper proposes and compares five methods for phase estimation to measure
      slight change of chest movement with respiration using a dual type microwave
      Doppler sensor. A body direction to the sensor affects the performance of the
      respiration measurement, because microwave reflection is sensitive to the surface
      direction. The phase estimation from two sensor signals is the most important
      part to measure respiration. Thus, we developed new five methods for phase
      estimation. These methods were evaluated by calculating correlation coefficients
      between estimated waveforms and reference ones. The results demonstrated that the
      phase estimation based on least square method is the best for respiration
      measurement with respect to both waveform estimation accuracy and calculation
      time. 

PMID- 24111291
TI  - Subsequence dynamic time warping as a method for robust step segmentation using
      gyroscope signals of daily life activities.
AB  - The segmentation of gait signals into single steps is an important basis for
      objective gait analysis. Only a precise detection of step beginning and end
      enables the computation of step parameters like step height, variability and
      duration. A special challenge for the application is the accurateness of such an
      algorithm when based on signals from daily live activities. In this study,
      gyroscopes were attached laterally to sport shoes to collect gait data. For the
      automated step segmentation, subsequence Dynamic Time Warping was used. 35
      healthy controls and ten patients with Parkinson's disease performed a four times
      ten meter walk. Furthermore 4 subjects were recorded during different daily life
      activities. The algorithm enabled counting steps, detecting precisely step
      beginning and end and rejecting other movements. Results showed a recognition
      rate of steps during ten meter walk exercises of 97.7% and in daily life
      activities of 86.7%. The segmentation procedure can be used for gait analysis
      from daily life activities and can constitute the basis for computation of
      precise step parameters. The algorithm is applicable for long-term gait
      monitoring as well as for analyzing gait abnormalities.

PMID- 24111292
TI  - A mobile-health application to detect wandering patterns of elderly people in
      home environment.
AB  - Wandering is a common and risky behavior in people with dementia (PWD). In this
      paper, we present a mobile healthcare application to detect wandering patterns in
      indoor settings. The application harnesses consumer electronics devices including
      WiFi access points and mobile phones and has been tested successfully in a home
      environment. Experimental results show that the mobile-health application is able
      to detect wandering patterns including lapping, pacing and random in real-time.
      Once wandering is detected, an alert message is sent using SMS (Short Message
      Service) to attending caregivers or physicians for further examination and timely
      interventions. 

PMID- 24111293
TI  - Body weight-normalized Energy Expenditure estimation using combined activity and
      allometric scaling clustering.
AB  - Wearable sensors have great potential for accurate estimation of Energy
      Expenditure (EE) in daily life. Advances in wearable technology (miniaturization,
      lower costs), and machine learning techniques as well as recently developed self
      monitoring movements, such as the Quantified Self, are facilitating mass
      adoption. However, EE estimations are affected by a person's body weight (BW). BW
      is a confounding variable preventing meaningful individual and group comparisons.
      In this paper we present a machine learning approach for BW normalization and
      activities clustering. In our approach to activity-specific EE modeling, we adopt
      a genetic algorithm-based clustering scheme, not only based on accelerometer
      (ACC) features, but also on allometric coefficients derived from 19 subjects
      performing a wide set of lifestyle and gym activities. We show that our approach
      supports making comparisons between individuals performing the same activities
      independently of BW, while maintaining accuracy in the EE estimate. 

PMID- 24111294
TI  - Estimation of feature importance for food intake detection based on Random
      Forests classification.
AB  - Selection of the most representative features is important for any pattern
      recognition system. This paper investigates the importance of time domain (TD)
      and frequency domain (FD) features used for automatic food intake detection in a
      wearable sensor system by using Random Forests classification. Features were
      extracted from signals collected using 3 different sensor modalities integrated
      into the Automatic Ingestion Monitor (AIM): a jaw motion sensor, a hand gesture
      sensor and an accelerometer. Data was collected from 12 subjects wearing AIM in
      free-living for a 24-hr period where they experienced unrestricted intake.
      Features from the sensor signals were used to train the Random Forests classifier
      that estimated the importance of each feature as part of the training process.
      Results indicated that FD features from the jaw motion signal and TD features
      from the accelerometer signal were the most relevant features for food intake
      detection. 

PMID- 24111295
TI  - On the impact of arousals on the performance of sleep and wake classification
      using actigraphy.
AB  - We evaluated the impact of arousals on the performance of actigraphy-based
      sleep/wake classification. Using a dataset of 15 healthy adults and a threshold
      optimized for this task we found that the percentage of sleep epochs with
      activity counts above that threshold was significantly larger in epochs with and
      following arousals. We also found that 41.1% of all false positive
      classifications occurred in these epochs. Finally, we determined that excluding
      these epochs from the evaluation led to a maximum precision increase of 17.2%.
      Considering wake detections in those epochs as correct led to a maximum precision
      increase of 31.3%. We concluded that unless arousals can be automatically
      identified or at least distinguished from wake, the performance of actigraphy
      based sleep/wake classifiers is limited by their presence. 

PMID- 24111296
TI  - Simultaneous determination of hemolysis and hematocrit in extracorporeal
      circulation by plasma surface reflectance spectroscopy.
AB  - To achieve quantitative non-invasive optical diagnosis of blood abnormalities
      during extracorporeal circulation therapies, plasma surface reflectance
      spectroscopy was developed by implementing oblique-incidence optical fiber
      reflectometry on the surface of circulating blood. The reflected light in the
      wavelength range from 450 to 600 nm changed with respect to the plasma free
      hemoglobin level and could be used to quantify the free hemoglobin at an accuracy
      of 5.7 +/- 3.5 mg/dL. In contrast, the spectrum did not changed by varying the
      hematocrit. In the wavelength range from 600 to 800 nm, the obtained spectrum was
      affected by both the hematocrit change and hemolysis. The linear correlation
      between the hematocrit value and the spectrum was confirmed at R(2) = 0.99. The
      feasibility of determining of the hematocrit of arbitrary hemolyzed blood was
      confirmed. The developed system permits the extraction of the optical
      characteristics of both plasma and red blood cells without centrifugation. The
      study establishes non-invasive optical diagnostics capable of analyzing the
      optical properties of both plasma and red blood cells.

PMID- 24111297
TI  - Hybrid sparse regularization for magnetic resonance spectroscopy.
AB  - Magnetic resonance spectroscopy imaging (MRSI) is a powerful non-invasive tool
      for characterising markers of biological processes. This technique extends
      conventional MRI by providing an additional dimension of spectral information
      describing the abnormal presence or concentration of metabolites of interest.
      Unfortunately, in vivo MRSI suffers from poor signal-to-noise ratio limiting its
      clinical use for treatment purposes. This is due to the combination of a weak MR
      signal and low metabolite concentrations, in addition to the acquisition noise.
      We propose a new method that handles this challenge by efficiently denoising MRSI
      signals without constraining the spectral or spatial profiles. The proposed
      denoising approach is based on wavelet transforms and exploits the sparsity of
      the MRSI signals both in the spatial and frequency domains. A fast proximal
      optimization algorithm is then used to recover the optimal solution. Experiments
      on synthetic and real MRSI data showed that the proposed scheme achieves superior
      noise suppression (SNR increase up to 60%). In addition, this method is
      computationally efficient and preserves data features better than existing
      methods. 

PMID- 24111298
TI  - Analyzing the information distribution in the fMRI measurements by estimating the
      degree of locality.
AB  - In this study, we propose a new method for analyzing and representing the
      distribution of discriminative information for data acquired via functional
      Magnetic Resonance Imaging (fMRI). For this purpose, we form a spatially local
      mesh with varying size, around each voxel, called the seed voxel. The
      relationship among each seed voxel and its neighbors is estimated using a linear
      regression model by minimizing the square error. Then, we estimate the optimal
      mesh size that represents the connections among each seed voxel and its
      surroundings by minimizing Akaike's Final Prediction Error (FPE) with respect to
      the mesh size. The degree of locality is represented by the optimum mesh size.
      Our results indicate that the local mesh size with the highest discriminative
      power varies across individual participants. The proposed method was tested on an
      fMRI study consisting of item recognition (IR) and judgment of recency (JOR)
      tasks. For each participant, the estimated arc weights of each local mesh with
      different mesh size are used to classify the type of memory judgment (i.e.IR or
      JOR). Classification accuracy for each participant was derived using k-Nearest
      Neighbor (k-NN) method. The results indicate that the proposed local mesh model
      with optimal mesh size can successfully represent discriminative information for
      neuroimaging data. 

PMID- 24111299
TI  - A method for quantitative SEMG decomposition and MUAP classification during
      voluntary isovelocity elbow flexion.
AB  - The purpose of this study was to develop an algorithm for surface electromyogram
      (SEMG) decomposition and classification of surface motor unit (MU) action
      potential (MUAP) detected during isovelocity elbow flexion. In our proposed
      algorithm, firstly the measured SEMG was extracted for 3 seconds by every 1.5
      seconds. SEMG was decomposed with Independent Component Analysis (ICA) technique,
      and classified with template matching. Finally, the MUAP trains were identified
      under the firing time of the MUAPs classified in each extracted period. The SEMG
      was measured from the biceps short head muscle during voluntary elbow flexion of
      0 to 90 degrees at constant velocity 9 degree/s against a constant load torque of
      10%MVC and the MUAPs were classified with our proposed algorithm. As a result,
      calculated MUs firing rates were almost same as the results in the previous
      studies. It was shown that the proposed algorithm was useful for decomposing SEMG
      detected during flexion movements.

PMID- 24111300
TI  - Representation of cognitive processes using the minimum spanning tree of local
      meshes.
AB  - A new graphical model called Cognitive Process Graph (CPG) is proposed, for
      classifying cognitive processes based on neural activation patterns which are
      acquired via functional Magnetic Resonance Imaging (fMRI) in brain. In the CPG,
      first local meshes are formed around each voxel. Second, the relationships
      between a voxel and its neighbors in a local mesh, which are estimated by using a
      linear regression model, are used to form the edges among the voxels (graph
      nodes) in the CPG. Then, a minimum spanning tree (MST) of the CPG which spans all
      the voxels in the region of interest is computed. The arc weights of the MST are
      used to represent the underlying cognitive processes. The proposed method reduces
      the curse of dimensionality problem that is caused by very large dimension of the
      feature space of the fMRI measurements, compared to number of instances. Finally,
      the arc weights computed over the path of the MST called MST-Features (MST-F) are
      used to train a statistical learning machine. The proposed method is tested on a
      recognition memory experiment, including data pertaining to encoding and
      retrieval of words belonging to ten different semantic categories. Two popular
      classifiers, namely k-Nearest Neighbor (k-NN) and Support Vector Machine (SVM),
      are trained in order to predict the semantic category of the item being
      retrieved, based on activation patterns during encoding. The classification
      performance of the proposed learning modelis superior to the classical multi
      voxel pattern analysis (MVPA) methods for the underlying cognitive process. 

PMID- 24111301
TI  - Prediction of chronic obstructive pulmonary disease exacerbation using
      physiological time series patterns.
AB  - Chronic obstructive pulmonary disease (COPD) is responsible for significant
      morbidity and mortality worldwide. Recent clinical research has indicated a
      strong association between physiological homeostasis and the onset of COPD
      exacerbation. Thus the analysis of these variables may yield a means of
      predicting a COPD exacerbation in the near future. However, the accuracy of
      existing prediction methods based on statistical analysis of periodic snapshots
      of physiological variables is still far from satisfactory, due to lack of
      integration of long-term and interactive effects of the physiological variables.
      Therefore, developing a relatively accurate method for predicting COPD
      exacerbation is an outstanding challenge. In this paper, a regression-based
      machine learning technique was developed, using trend pattern variables extracted
      from COPD patients' longitudinal physiological records, to classify subjects into
      "low-risk" and "high-risk" categories, indicating their risk of suffering a COPD
      exacerbation event. Experimental results from cross validation assessment of the
      classifier model show an average accuracy of 79.27% using this method. 

PMID- 24111302
TI  - An effective wavelet strategy for the trend prediction of physiological time
      series with application to pHealth systems.
AB  - This work proposes a wavelet decomposition based scheme to estimate the evolution
      trend of physiological time series. The scheme does not involve the explicit
      development of a model and is essentially supported on the hypothesis that future
      evolution of a biosignal can be estimated from similar historic patterns. The
      strategy considers an a-trous wavelet decomposition, where the most
      representative trends are extracted from the historic similar patterns. Then, a
      set of distance-based measures able to assess the prediction likelihood of each
      representative trend, is introduced. From these measures and through an
      optimization process, a subset of these trends is selected and aggregated to
      derive the required time series evolution trend. The effectiveness of the
      methodology is validated in the prediction of blood pressure signals collected in
      two telemonitoring studies: TEN-HMS and MyHeart. Additionally, Friedman and
      Nemenyi statistics tests are implemented to rank several methods, confirming the
      value of the proposed strategy. 

PMID- 24111303
TI  - Multiple time-lag canonical correlation analysis for removing muscular artifacts
      in EEG.
AB  - In this work, a new approach for joint blind source separation (BSS) of datasets
      at multiple time lags using canonical correlation analysis (CCA) is developed for
      removing muscular artifacts from electroencephalogram (EEG) recordings. The
      proposed approach jointly extracts sources from each dataset in a decreasing
      order of between-set source correlations. Muscular artifact sources that
      typically have lowest between-set correlations can then be removed. It is shown
      theoretically that the proposed use of CCA on multiple datasets at multiple time
      lags achieves better BSS under a more relaxed condition and hence offers better
      performance in removing muscular artifacts than the conventional CCA. This is
      further demonstrated by experiments on real EEG data. 

PMID- 24111304
TI  - Smoothness constraint for cortical dipolar sources estimation.
AB  - In the last decade, a wide range of approaches have been proposed to estimate the
      activity of physiological sources from multi-channel electroencephalographic
      (EEG) data. Two utterly different directions can be distinguished: brain source
      imaging (BSI) and blind source separation (BSS). While the first approach is
      based on the inversion of a given forward model, the latter blindly decomposes
      the EEG mixing by optimization of a contrast function excluding any physiological
      priors on the problem. All these methods have proven their ability in
      reconstructing efficiently the source activities in some well adapted situations.
      Nevertheless, the synthesis of a reliable lead field model for BSI is
      computationally demanding, and the criterion to be optimized in BSS are often
      inadequate with regards to the physiology of the problem. In this paper, a
      compromise between these two methodological trends is introduced. A BSS method is
      described taking account of physiological knowledge on the projection of the
      sources on the scalp map in conjunction with strong priors on the localization of
      the recorded sources. This estimation method is demonstrated to lead to a
      generalization of the classical Hjorth's laplacian montage, and provides
      satisfactory simulation results when the appropriate configurations on the
      sources are met. 

PMID- 24111305
TI  - Method for removing motion artifacts from fNIRS data using ICA and an
      acceleration sensor.
AB  - Independent component analysis (ICA) is one of the most preferred methods for
      removing motion artifacts from functional near-infrared spectroscopy (fNIRS)
      data. In this method, fNIRS signal is separated into some components by ICA. The
      component which has high correlation between fNIRS signal and motion artifact is
      determined. This component is removed and fNIRS signal without motion artifact
      effect is derived. However, because of the influence of blood flow, fNIRS data
      are often delayed in time compared with the acceleration sensor data. Therefore,
      the correlation is reduced, and it is difficult to determine whether the
      component has been derived from the motion artifact. We here propose a method for
      removing the motion artifact using ICA, which considers the time delay in the
      fNIRS data. In this proposed method, ICA is performed multiple times, shifting
      the start time of the fNIRS data with each repeat. Then, only the best correlated
      result is adopted for comparison with the acceleration sensor data. To examine
      the effectiveness of this method, its results were compared with the results
      obtained without considering the time delay. It was found that the proposed
      method improved that accuracy of removing the motion artifact. 

PMID- 24111306
TI  - Comparison of the AMICA and the InfoMax algorithm for the reduction of
      electromyogenic artifacts in EEG data.
AB  - Electromyogenic or muscle artifacts constitute a major problem in studies
      involving electroencephalography (EEG) measurements. This is because the rather
      low signal activity of the brain is overlaid by comparably high signal activity
      of muscles, especially neck muscles. Hence, recording an artifact-free EEG signal
      during movement or physical exercise is not, to the best knowledge of the
      authors, feasible at the moment. Nevertheless, EEG measurements are used in a
      variety of different fields like diagnosing epilepsy and other brain related
      diseases or in biofeedback for athletes. Muscle artifacts can be recorded using
      electromyography (EMG). Various computational methods for the reduction of muscle
      artifacts in EEG data exist like the ICA algorithm InfoMax and the AMICA
      algorithm. However, there exists no objective measure to compare different
      algorithms concerning their performance on EEG data. We defined a test protocol
      with specific neck and body movements and measured EEG and EMG simultaneously to
      compare the InfoMax algorithm and the AMICA algorithm. A novel objective measure
      enabled to compare both algorithms according to their performance. Results showed
      that the AMICA algorithm outperformed the InfoMax algorithm. In further research,
      we will continue using the established objective measure to test the performance
      of other algorithms for the reduction of artifacts.

PMID- 24111307
TI  - An efficient VLSI implementation of on-line recursive ICA processor for real-time
      multi-channel EEG signal separation.
AB  - This paper presents an efficient VLSI implementation of on-line recursive ICA
      (ORICA) processor for real-time multi-channel EEG signal separation. The proposed
      design contains a system control unit, a whitening unit, a singular value
      decomposition unit, a floating matrix multiply unit and, and an ORICA weight
      training unit. Because the input sample rate of the ORICA processor is 128 Hz,
      the ORICA processor should produce independent components before the next sample
      is input in 1/128 s. Under the timing constraints of commutating multi-channel
      ORICA in real time, the design of the ORICA processor is a mixed architecture,
      which is designed as different hardware parallelism according to the complexity
      of processing units. The shared arithmetic processing unit and shared register
      can reduce hardware complexity and power consumption. The proposed design is
      implemented used TSMC 90 nm CMOS technology with 8-channel EEG processing in 128
      Hz sample rate of raw data and consumes 2.827 mW at 50 MHz clock rate. The
      performance of the proposed design is also shown to reach 0.0078125 s latency
      after each EEG sample time, and the average correlation coefficient between the
      original source signals and extracted ORICA signals for each 1 s frame is 0.9763.

PMID- 24111308
TI  - Single channel blind source separation based local mean decomposition for
      biomedical applications.
AB  - Single Channel Blind Source Separation (SCBSS) is an extreme case of
      underdetermined (more sources and fewer sensors) Blind Source Separation (BSS)
      problem. In this paper, we propose a novel technique using Local Mean
      Decomposition (LMD) and Independent Component Analysis (ICA) combined with single
      channel BSS (LMD_ICA). First, the LMD was used to decompose the single channel
      source into a series of data sequences, which are called as Product Functions
      (PF), then, ICA algorithm was used to process PFs to get similar independent
      components and extract the original signals. A comparison was made between
      LMD_ICA and previously proposed single channel ICA method (EEMD_ICA). The real
      time experimental results demonstrated the advantage of the proposed single
      channel source separation method for artifact removal and in biomedical source
      separation applications. 

PMID- 24111310
TI  - Silicon Nanotweezers with a microfluidic cavity for the real time
      characterization of DNA damage under therapeutic radiation beams.
AB  - We report the biomechanical characterization of lambda-DNA bundle exposed to a
      therapeutic radiation beam by silicon Nanotweezers. The micromechanical device
      endures the harsh environment of radiation beams, and still retains molecular
      level detection accuracy. The real-time DNA bundle degradation is observed in
      terms of biomechanical stiffness and viscosity reduction, both in air and in
      solution. These results pave the way for both fundamental and clinical studies of
      DNA degradation mechanisms under ionizing radiation for improved tumor treatment.

PMID- 24111312
TI  - Non-planar and flexible chip technology for biomedical applications.
AB  - We report a novel non-planar flexible silicon chip technology by means of
      patterning thin films of high residual stress on top of shaped thin silicon
      substrate. High residual stresses of thin films make thin chip deform into
      designed three-dimensional shapes. In this study, a series of patterned stress
      films and "petal-like" chips were fabricated and analyzed. Large curvatures can
      also be formed and maintained by the packaging process bonding the chips to
      constraining elements such as thin-film polymer ring structures. As a
      demonstration, a CMOS image-sensing retina chip is made into a contact-lens shape
      conforming to a human eyeball 12.5 m in radius. This non-planar and flexible chip
      technology provides a desirable device surface interface to soft or non-planar
      bio surfaces and opens up possibilities for many biomedical applications.

PMID- 24111311
TI  - Nanopore single-molecule dielectrophoretic detection of cancer-derived microRNA
      biomarkers.
AB  - The nanopore-based single-molecule biosensor has been extensively investigated
      for various biomedical detections. It has demonstrated the potential in gene
      sequencing and diagnosis-oriented biomarker detection such as microRNAs. In real
      time detection, however, samples extracted from bio-fluids contain various non
      target nucleic acids components. These components can cause severely influence
      the target detection accuracy. We have discovered that a polycationic probe can
      solve this issue. The polycationic peptide domain of the probe can separate the
      target probe complex from free nucleic acids, and only lead the complex into the
      pore, therefore realizing simultaneous enrichment and detection of target
      microRNAs. This study establishs a universal approach to detecting any short
      pathogenic nucleic acids fragment in complex samples. 

PMID- 24111313
TI  - Threshold levels for wettability in nano- and micro-meter periodic structures.
AB  - The purposes of this study are to clarify the relationship between surface
      wettability and the pitch and size of periodic structures on the surface and to
      determine the thresholds at which the wettability switches from being hydrophobic
      to hydrophilic. To this various nano- and micro-meter scale periodic structures
      were fabricated. By applying a fine periodic structure to the surface, the
      wettability can be controlled between + 50 degrees  (hydrophobic) and -55 degrees
      (hydrophilic). The pitch of the periodic structure at which the wettability
      switches from hydrophilic to hydrophobic was found to between 500 and 1,000 nm.
      Additionally, the height of the periodic structure at which the wettability
      switches from hydrophobic to hydrophilic was found to between 300 and 700 nm. 

PMID- 24111314
TI  - Softening of the mouse zona pellucida during oocyte maturation.
AB  - A change in the elasticity and the resistance to dissolution of the mouse zona
      pellucida (ZP) was quantitatively evaluated at immature germinal vesicle (GV),
      mature metaphase II (MII) and fertilized pronuclear (PN) stages. Young's modulus
      of the ZP was measured using a micro tactile sensor (MTS), a highly sensitive
      resonator-based sensor for a micro scale elasticity measurement. 0.25% alpha
      chymotrypsin was used for the ZP dissolution assay. The results of measuring the
      ZP elasticity and the dissolution time clearly showed that the ZP softened during
      oocyte maturation and the ZP hardened after fertilization. The results indicate
      that the amount of the zona softening can be a criterion to evaluate oocyte
      quality for the selection of top quality mature oocyte before in vitro
      fertilization (IVF) treatment. 

PMID- 24111315
TI  - Simulating the role of anisotropy in human atrial cardioversion.
AB  - This computational study quantifies the effectiveness of feedback controlled low
      energy cardioversion in the anisotropic human atria. An established biophysical
      human cell model was adopted to reproduce Control and chronic atrial fibrillation
      (CAF) action potentials. The cell model was combined with a detailed human atrial
      geometry to construct a 3D realistic human atrial model. Scroll waves were
      simulated under Control and CAF conditions and the cardioversion parameters of
      stimulation strength and pacing duration were evaluated for scroll wave
      termination. Scroll waves were initiated at two locations in the atria to elicit
      the effects of scroll wave location. The role of anisotropy was highlighted by
      comparison to results from the isotropic case. Under Control conditions, scroll
      wave self-termination was rapid in the anisotropic case. Under CAF conditions,
      anisotropy caused the initiated scroll wave to degenerate into multiple scrolls
      with each evolving erratically or pinning to anatomical defects. The
      cardioversion successfully terminated scroll waves within 10 s, but the stimulus
      strength had a strong correlation to the location of the scroll wave. The low
      energy stimulation strength was always lower than the threshold stimulus.
      Anisotropy plays an important role in atrial electrical properties. Anisotropy
      aggravates CAF and leads to high frequency atrial pacing. The efficacy of
      cardioversion is significantly affected by anisotropy.

PMID- 24111316
TI  - Simulating cell apoptosis induced sinus node dysfunction.
AB  - Sinus node dysfunction (SND) is correlated to the pacemaker sinoatrial node (SAN)
      cell apoptosis. This study explores the effect of such a dysfunctional SAN on
      electrical propagation into neighboring atrial tissue. The Fenton Karma model was
      extended to simulate mouse SAN and atrial cell action potentials. The cell models
      were incorporated into a 2D model consisting of a central SAN region surrounded
      by atrial tissue. The intercellular gap junctional coupling, as quantified by the
      diffusion constant, was estimated to give conduction speeds as observed in mouse
      atrial tissue. The size of mouse SAN pacemaking region was estimated using the 2D
      model. In multiple simulations, the effects of an increasing proportion of
      apoptotic pacemaker cells on atrial tissue pacing were simulated and quantified.
      The SAN size that gave a basal mouse atrial cycle length (ACL) of 295 ms was
      found to be 0.6 mm in radius. At low pacemaker cell apoptosis proportion, there
      was a drastic increase of ACL. At modest increase in the number of apoptotic
      cells, bradycardia was observed. The incidence of sinus arrest was also found to
      be high. When the number of apoptotic cells were 10% of the total number of
      pacemaking cells, all pacemaking was arrested. Phenomenological models have been
      developed to study mouse atrial electrophysiology and confirm experimental
      findings. The results show the significance of cell apoptosis as a major
      mechanism of SND.

PMID- 24111317
TI  - Modeling the different sections of the cardiac conduction system to obtain
      realistic electrocardiograms.
AB  - The cardiac conduction system is divided in different sections that play an
      important role in the cardiac depolarization sequence and define the morphology
      of the electrocardiogram. In this study we have built several configurations for
      each section based on anatomical descriptions. The effect of the morphology of
      the bundle branches, and the density of both Purkinje branches and Purkinje
      myocardial junctions (PMJ) has been studied by comparing the pseudo-ECGs obtained
      with the standard precordial leads of the electrocardiogram. A functional model
      for the PMJs based on the existence of a conduction adaptation layer is also
      presented. Simulation results showed a large influence of the His bundle and
      bundle branches in the pseudo-ECG and helped to elucidate the most appropriate
      morphology. The functional PMJ model allowed bidirectional communication between
      the conduction system and the myocardium with realistic transmission delays
      between both mediums. These results can help to improve current conduction system
      models and improve depolarization sequences of activation in the ventricles. 

PMID- 24111318
TI  - Simulation study of complex action potential conduction in atrioventricular node.
AB  - The atrioventricular (AV) node, which is located between the atria and ventricles
      of the heart, acts as important roles in cardiac excitation conduction between
      the two chambers. Although there are multiple conduction pathways in the AV node,
      the structure of the AV node has not been clarified. In this study, we
      constructed a one-dimensional model of the AV node and simulated excitation
      conduction between the right atrium and the bundle of His via the AV node. We
      also investigated several characteristics of the AV node: (1) responses of the AV
      node to high-rate excitation in the right atrium, (2) the AV nodal reentrant beat
      induced by premature stimulus, and (3) ventricular rate control during atrial
      fibrillation with various methods. Our simulation results suggest that multiple
      conduction pathways act as important roles in controlling the ventricular rate.
      The one-dimensional model constructed in this study may be useful to analyze
      complex conduction patterns in the AV node. 

PMID- 24111319
TI  - A study on the relationship between electrical transmural heterogeneity and
      ventricular energetics.
AB  - In this study, we use cardiovascular simulation to gain new insights on the
      correlation between electrical heterogeneity and ventricular energetics. Although
      there are numerous in vivo and in vitro studies on the electrical heterogeneity
      within the ventricular myocardium, not much attention has been directed to its
      correlation to cardiovascular mechanics, because of difficulties in
      simultaneously observing and analyzing multiple spatial scales (the cell, the
      organ, and the system). We performed simulations with two cardiovascular
      simulation models, one which uses different myocardial cell models for the
      epicardial, endocardial, and mid-myocardial cells, and another which uses a
      homogeneous model throughout the entire myocardium. The epicardial, endocardial,
      and midmyocardial cell models were created by parametrically tuning a homogenous
      cell model. From the cardiovascular simulation we obtained pressure-volume loops
      which were used to calculate cardiovascular energetic efficiency and myocardial
      contractility. We found that energetic efficiency is higher in the electrically
      heterogeneous model.

PMID- 24111320
TI  - Comparison of simulated and clinical intracardiac electrograms.
AB  - Intracardiac electrograms are the key in understanding, interpretation and
      treatment of cardiac arrhythmias. However, electrogram morphologies are strongly
      variable due to catheter position, orientation and contact. Simulations of
      intracardiac electrograms can improve comprehension and quantification of
      influencing parameters and therefore reduce misinterpretations. In this study
      simulated intracardiac electrograms are analyzed regarding tilt angles of the
      catheter relative to the propagation direction, electrode tissue distances as
      well as clinical filter settings. Catheter signals are computed on a realistic 3D
      catheter geometry using bidomain simulations of cardiac electrophysiology.
      Thereby high conductivities of the catheter electrodes are taken into account.
      For validation, simulated electrograms are compared with in vivo electrograms
      recorded during an EP-study with direct annotation of catheter orientation and
      tissue contact. Good agreement was reached regarding timing and signal width of
      simulated and measured electrograms. Correlation was 0.92+/-0.07 for bipolar,
      0.92+/-0.05 for unipolar distal and 0.80 +/- 0.12 for unipolar proximal
      electrograms for different catheter orientations and locations. 

PMID- 24111321
TI  - Measuring leg movements during sleep using accelerometry: comparison with EMG and
      piezo-electric scored events.
AB  - Periodic Limb Movements during Sleep (PLMS) can cause significant disturbance to
      sleep, resulting in daytime sleepiness and reduced quality of life. In
      conventional clinical practice, PLMS are measured using overnight electromyogram
      (EMG) of the tibialis anterior muscle, although historically they have also been
      measured using piezo-electric gauges placed over the muscle. However, PLMS counts
      (PLM index) do not correlate well with clinical symptomology. In this study, we
      propose that because EMG and piezo derived signals measure muscle activation
      rather than actual movement, they may count events with no appreciable movement
      of the limb and therefore no contribution to sleep disturbance. The aim of this
      study is thus to determine the percentage of clinically scored limb movements
      which are not associated with movement of the great toe measured using
      accelerometry. 9 participants were studied simultaneously with an overnight
      diagnostic polysomnogram (including EMG and piezo instrumentation of the right
      leg) and high temporal resolution accelerometry of the right great toe. Limb
      movements were scored, and peak acceleration during each scored movement was
      quantified. Across the participant population, 54.9% (range: 26.7-76.3) and 39.0%
      (range: 4.8-69.6) of limb movements scored using piezo and EMG instrumentation
      respectively, were not associated with toe movement measured with accelerometry.
      If sleep disturbance is the consequence of the limb movements, these results may
      explain why conventional piezo or EMG derived PLMI is poorly correlated with
      clinical symptomology. 

PMID- 24111322
TI  - Using acoustics to estimate inspiratory flow rate and drug removed from a dry
      powder inhaler.
AB  - Morbidity and mortality rates of chronic respiratory diseases such as asthma and
      chronic obstructive pulmonary disease (COPD) are rising. There is a strong
      requirement for more effective management of these chronic diseases. Dry powder
      inhalers (DPIs) are one kind of devices currently employed to deliver medication
      aimed at controlling asthma and COPD symptoms. Despite their proven effectiveness
      when used correctly, some patients are unable to reach the inspiratory flow rate
      required to remove medication from the breath actuated devices and as a result,
      the medication does not reach the airways. This study employs an acoustic
      recording device, attached to a common DPI to record the audio signals of
      simulated inhalations. A rotameter was used to measure the flow rate through the
      inhaler while a milligram weighing scale was used to measure the amount of drug
      removed from each simulated inhalation. It was found that a strong correlation
      existed (R(2)>0.96) when average power, median amplitude, root mean square and
      mean absolute deviation were used to predict peak inspiratory flow rate. At a
      flow of 30 L/Min (mean absolute deviation=0.0049), it was found that 77% of the
      total emitted dose was removed from the inhaler. Results indicate that acoustic
      measurements may be used in the prediction of inspiratory flow rate and quantity
      of medication removed from an inhaler.

PMID- 24111323
TI  - Automatic snoring detection from nasal pressure data.
AB  - This study presents a method for automatic snoring detection from a nasal
      pressure data. First, a spectrogram analysis was performed in order to obtain
      information about the spectral characteristic of nasal pressure data. The
      automatic method is based on a simple signal filtering and short-time energy
      technique. Fifteen patients were participated in order to evaluation the
      performance of the proposed method. Results are compared with manually labeled
      snoring events by watching video records. The sensitivity and positive
      predictivity value were 93.73% and 93.70%, respectively. The results in this
      study could provide sleep experts with the method to objectively monitor sleep
      disordered breathing in CPAP system or PSG study. 

PMID- 24111324
TI  - Validation of automatic CPAP leak algorithm.
AB  - Obstructive Sleep Apnoea (OSA) is a prevalent disease. Reliable estimation of
      respiratory parameters by devices used to treat OSA is important for therapy
      initiation and maintenance. This is achieved by estimating patient flow in the
      presence of inadvertent leak from the total flow measured by the device. A method
      of validating the patient flow estimation of an Automatic Continuous Positive
      Airway Pressure (APAP) device is described. Novel techniques of a multi-composite
      simulant head and recorded patient flows are used. The APAP device tested was
      shown to reliably estimate patient flow across a range of therapy pressures, leak
      conditions and breath types. 

PMID- 24111326
TI  - A frequency domain analysis of respiratory variations in the seismocardiogram
      signal.
AB  - The seismocardiogram (SCG) signal traditionally measured using a chest-mounted
      accelerometer contains low-frequency (0-100 Hz) cardiac vibrations that can be
      used to derive diagnostically relevant information about cardiovascular and
      cardiopulmonary health. This work is aimed at investigating the effects of
      respiration on the frequency domain characteristics of SCG signals measured from
      18 healthy subjects. Toward this end, the 0-100 Hz SCG signal bandwidth of
      interest was sub-divided into 5 Hz and 10 Hz frequency bins to compare the
      spectral energy in corresponding frequency bins of the SCG signal measured during
      three key conditions of respiration--inspiration, expiration, and apnea.
      Statistically significant differences were observed between the power in ensemble
      averaged inspiratory and expiratory SCG beats and between ensemble averaged
      inspiratory and apneaic beats across the 18 subjects for multiple frequency bins
      in the 10-40 Hz frequency range. Accordingly, the spectral analysis methods
      described in this paper could provide complementary and improved classification
      of respiratory modulations in the SCG signal over and above time-domain SCG
      analysis methods.

PMID- 24111327
TI  - The effect of force feedback on transfer of learning between the arms during
      bimanual reaching.
AB  - This study examined the effects of simultaneous learning of a force-field by two
      arms on transfer of learning during bimanual reaching. Subjects performed three
      reaching tasks by both arms: (1) with only dominant arm experiencing the force
      field, (2) with only the nondominant arm experiencing the force-field, and (3)
      with both arms experiencing the same (intrinsic) force-field as in tasks (1) and
      (2). The results indicated that the rate of motor adaptation was greater when
      both arms experienced the intrinsic force-field than when only one arm
      experienced the force-field. Transfer of learning occurred in both directions due
      to the intrinsic force-field applied to the other arm: from the dominant arm to
      the nondominant arm and from the nondominant arm to the dominant arm. 

PMID- 24111328
TI  - The effect of the direction of force-fields on transfer of learning between the
      arms during bimanual reaching.
AB  - This study examined the effects of force-field direction (extrinsic vs.
      intrinsic) on transfer of learning during bimanual reaching. Subjects performed
      bimanual reaching tasks in two force-fields: (1) intrinsic and (2) extrinsic.
      Motor adaptation of each arm was determined by measuring the deviation of the
      hand trajectory from a straight line. It was found that rate of motor adaptation
      of the dominant arm was the same in the two tasks. For the nondominant arm, the
      rate of motor adaptation was greater during reaching in the intrinsic force-field
      than in the extrinsic force-field. It is concluded that the load-related sensory
      feedback from the dominant arm interfered with motor adaptation of the
      nondominant arm. 

PMID- 24111329
TI  - Human reach-to-grasp compensation with object pose uncertainty.
AB  - This paper examined how humans alter reach-to-grasp behavior to compensate for
      environmentally-induced object orientation uncertainty. We used a novel motion
      tracking framework to capture hand-object interactions, as well as a custom
      cylindrical object to detect contacts. Subjects were instructed to reach, grasp,
      and lift the object with or without vision. The orientation of the object was
      randomly changed on each trial. We hypothesized subjects would use a reach-to
      grasp strategy that minimizes post-contact adjustments. However, our results
      indicate that (1) subjects are more likely to use the hand as a sensing apparatus
      prior to contact, and (2) the reach-to-grasp kinematics may be optimized for
      efficient sensing of object orientation. Our findings could provide potential
      solution to efficient tactile sensing for robotic hand in unstructured
      environment. 

PMID- 24111330
TI  - Improved discrete Fourier transform based spectral feature for surface
      electromyogram signal classification.
AB  - An improved discrete Fourier transform (iDFT) is presented in this study as a
      novel feature for surface electromyogram (sEMG) pattern classification. It
      employs the principle that the spectrum of sEMG signals changes regarding
      different motions. iDFT feature focuses on global information of local bands to
      increase the inter-class distance. The experiment results showed that iDFT
      feature had a better separability than two other spectral features, auto
      regression (AR) and Power spectral density (PSD), both on experienced and
      inexperienced subjects. The optimal bandwidth is between 30 and 50 Hz and
      influence of division methods is not significant. With the low computation cost
      and property of insensitivity to sampling frequency, our proposed method provides
      a competitive choice for prosthetic control. 

PMID- 24111331
TI  - Bio-robots automatic navigation with graded electric reward stimulation based on
      Reinforcement Learning.
AB  - Bio-robots based on brain computer interface (BCI) suffer from the lack of
      considering the characteristic of the animals in navigation. This paper proposed
      a new method for bio-robots' automatic navigation combining the reward generating
      algorithm base on Reinforcement Learning (RL) with the learning intelligence of
      animals together. Given the graded electrical reward, the animal e.g. the rat,
      intends to seek the maximum reward while exploring an unknown environment. Since
      the rat has excellent spatial recognition, the rat-robot and the RL algorithm can
      convergent to an optimal route by co-learning. This work has significant
      inspiration for the practical development of bio-robots' navigation with hybrid
      intelligence. 

PMID- 24111332
TI  - An SSVEP based BCI to control a humanoid robot by using portable EEG device.
AB  - Brain Computer Interfaces (BCIs) are systems that allow human subjects to
      interact with the environment by interpreting brain signals into machine
      commands. This work provides a design for a BCI to control a humanoid robot by
      using signals obtained from the Emotiv EPOC, a portable electroencephalogram
      (EEG) device with 14 electrodes and sampling rate of 128 Hz. The main objective
      is to process the neuroelectric responses to an externally driven stimulus and
      generate control signals for the humanoid robot Nao accordingly. We analyze
      steady-state visually evoked potential (SSVEP) induced by one of four groups of
      light emitting diodes (LED) by using two distinct signals obtained from the two
      channels of the EEG device which reside on top of the occipital lobe. An embedded
      system is designed for generating pulse width modulated square wave signals in
      order to flicker each group of LEDs with different frequencies. The subject
      chooses the direction by looking at one of these groups of LEDs that represent
      four directions. Fast Fourier Transform and a Gaussian model are used to detect
      the dominant frequency component by utilizing harmonics and neighbor frequencies.
      Then, a control signal is sent to the robot in order to draw a fixed sized line
      in that selected direction by BCI. Experimental results display satisfactory
      performance where the correct target is detected 75% of the time on the average
      across all test subjects without any training.

PMID- 24111333
TI  - Alpha-band rhythm modulation under the condition of subliminal face presentation:
      MEG study.
AB  - The human brain has two streams to process visual information: a dorsal stream
      and a ventral stream. Negative potential N170 or its magnetic counterpart M170 is
      known as the face-specific signal originating from the ventral stream. It is
      possible to present a visual image unconsciously by using continuous flash
      suppression (CFS), which is a visual masking technique adopting binocular
      rivalry. In this work, magnetoencephalograms were recorded during presentation of
      the three invisible images: face images, which are processed by the ventral
      stream; tool images, which could be processed by the dorsal stream, and a blank
      image. Alpha-band activities detected by sensors that are sensitive to M170 were
      compared. The alpha-band rhythm was suppressed more during presentation of face
      images than during presentation of the blank image (p=.028). The suppression
      remained for about 1 s after ending presentations. However, no significant
      difference was observed between tool and other images. These results suggest that
      alpha-band rhythm can be modulated also by unconscious visual images. 

PMID- 24111334
TI  - Steering timing prediction in a driving simulator task.
AB  - In this paper we present the preliminary results of a pioneering attempt to
      predict the timing of steering actions in a driving task from non-invasive EEG
      measurements. The experiment took place with the subjects driving a car at a
      constant speed on a simulated highway in a driving simulator. The EEG activity
      was analyzed during periods of straight driving and during lane change actions.
      Classifiers were built on the signals recorded over the motor areas for straight
      and pre-steering periods. The onset of the steering actions was detected on
      average 811 ms before the action with a 74.6% true positive rate.

PMID- 24111335
TI  - Basic study on a walking assist system with electrical stimulation for elderly
      people.
AB  - The purpose of this study is to examine the usefulness of a walking assist system
      using electrical stimulation. Thirty-two elderly people (18 men and 14 women)
      having no medical problems and five healthy young men participated in the study.
      The electrical stimulation was carried out in two cases: 1) hybrid training
      (HYBT) for the elderly subjects, 2) assisted walking aimed at eventual
      application in elderly individuals. The intensity of the electrical stimulation
      is 80% in case 1) and three patterns of 60%, 70%, and 80% of the measured maximum
      tolerable voltage (mMTV) in case 2). The HYBT effectiveness was the same or
      greater than that of weight machine training (WMT), and could improve the motor
      function of the lower limbs. During the assisted walking, the peak value of the
      vertical acceleration of the third lumber vertebra increased in contrast with the
      non-assisted walking. Steps and changes in the peak acceleration values in the
      sagittal plane also showed a tendency to increase due to the electrical
      stimulation. These results suggest that electrical stimulation can contribute to
      restore the weakened physical function of elderly individuals. The restoration
      will reduce the risk of falls and increase the daily activities.

PMID- 24111336
TI  - Variance between walking speed and neuropsychological test scores during three
      gait tasks across the Irish Longitudinal study on Aging (TiLDA) dataset.
AB  - This study investigated the relationship between neuropsychological test scores
      and gait speed in three gait tasks using baseline cross-sectional data from 4694
      healthy adults (54% women, age (mean+/-sd) 62.4+/-8.2) from The Irish
      Longitudinal study on Aging (TiLDA). Global cognition, short term memory, speed
      of processing, executive function and sustained attention were measured by a
      detailed battery of neuropsychological tests. Gait speed was recorded from a
      GaitRiteTM pressure sensing mat during a single walk and two dual walking tasks;
      dual cognitive walk (alternate letters) and dual motor walk (carrying a glass of
      water). Correlations between neuropsychological test scores and the three gait
      speed outcomes were investigated using univariate and multiple linear regressions
      models; firstly adjusting for age, gender, height, education and depression only
      and then including all neuropsychological test scores in the same regression
      model and adjusting as previously. It was found that short term memory, speed of
      processing and attention were significantly correlated with gait speed in all
      three gait conditions, with global cognition and executive function also
      significantly correlated with gait speed in the dual cognitive walk. The nature
      and complexity of the task performed affected gait speed with the addition of the
      cognitive task while walking causing a larger reduction in gait speed than the
      addition of the motor task. This indicates that for this healthy nationally
      representative population sample there is a link between neural processes
      involved in movement and cognition and this association differs depending on the
      gait task performed. 

PMID- 24111338
TI  - Assessment of visual space recognition in patients with visual field defects
      using head mounted display (HMD) system: case study with severe visual field
      defect.
AB  - For the quantitative assessment of visual field defects of cerebrovascular
      patients, we developed a new measurement system that could present various kinds
      of visual information to the patient. In this system, we use a head mounted
      display as the display device. The quantitative assessment becomes possible by
      adding the capability to measure the eye movement and the head movement
      simultaneously by means of a video apparatus of motion analysis. In our study, we
      examined the effectiveness of this system by applying it to a patient with
      serious visual field defects. The visual image of the reduced test paper was
      presented to the patient, the effect on his/her spatial recognition and eye
      movement was investigated. The results indicated the increase in the ration of
      visual search in the reduced side. With the reduced image, the decrease of the
      angular velocity of eye movement was recognized in the visual search in the
      defected side. In the motion analysis, the head movement was not observed while
      the eye movements appeared corresponding to each different conditions. This fact
      led us to confirm that the patient coped with this kind of test by the eye
      movement. In this analysis, the effectiveness and the usefulness of the developed
      system were confirmed that enables us to evaluate the abnormal and compensation
      movement of the eyes. 

PMID- 24111339
TI  - Similarity of muscle synergies in human walking and cycling: preliminary results.
AB  - Recent investigations on how the Motor System coordinates different tasks in
      humans have indicated that a low-dimensional structure of muscle synergies is
      sufficient to explain specific spatiotemporal components underlying such
      behaviors. In this work, we tested the hypothesis that pedaling and walking share
      common modular features by using the muscle synergies paradigm. Seven healthy
      subjects walked on a treadmill at their maximum speed and also cycled in an
      ergometer, set at the same walking cadence. EMG activity was recorded from 10
      muscles of the most dominant leg. A Non-Negative Matrix Factorization algorithm
      was applied to extract synergies. Four synergies were sufficient to explain 90%
      of the EMG variability during walking and cycling. There were statistically
      significant correlations (higher than 71%) across similar synergies for each task
      (walking and pedaling). These preliminary results support the hypothesis of
      modular control across different human motor tasks and may indicate that some
      synergies are shared amongst different rhythmic movements. 

PMID- 24111340
TI  - Study of variation in human upper body parameters and motion for use in robotics
      based simulation.
AB  - This paper reviews the variations in human upper body motion of subjects
      completing activities of daily living. This study was completed to serve as a
      reference to evaluate the quality of simulated of human motion. In this paper we
      define the variation in motion as the variation in subjects' parameters (link
      lengths), joint angles, and hand positions, for a given task. All of these
      variations are related by forward kinematic equations. Motion data from eight
      healthy right hand dominant adults performing three activities of daily living
      (brushing hair, drinking from a cup, and opening a door) were collected using an
      eight camera Vicon motion analysis system. Subject parameters were calculated
      using relative positions of functional joint center locations between segments.
      Joint angles were calculated by Euler angle rotations between body segments. Hand
      position was defined as the origin of the hand frame relative to the pelvis
      frame. The variance of recorded human motion was analyzed based on the standard
      deviations of subject parameters, joint angles, and hand positions. Variances in
      joint angles were found to be similar in magnitude to root mean squared error of
      kinematics based motion simulation. To evaluate the relative variance, the
      forward kinematic solutions of the trials were found after removing subject
      parameter variance and reducing joint angle variance. The variance in the forward
      kinematic solution was then compared to the recorded hand position variance.
      Reductions in subject parameter and joint angle variance produced a
      proportionally much smaller reduction in the calculated hand position variance.
      Using the average instead of individual subject parameters had only a small
      impact on hand position variance. Modifying joint angles to reduce variance had a
      greater impact on the calculated hand position variance than using average
      subject parameters, but was still a relatively small change. Future work will
      focus on using these results to create formalized procedures for quantifying the
      human likeness of artificial human motions, to serve as a basis for performance
      comparison between different methods. 

PMID- 24111341
TI  - Principles of human locomotion: a review.
AB  - In this article the principles of human locomotion are revisited and reviewed.
      This has been done in the framework of two European projects, where the
      elicitation of these mechanisms inform, on the one hand, the design of artificial
      bipedal walkers (H2R), and on the other hand the design of lower limb
      exoskeletons (BETTER) for rehabilitation of gait in post-stroke patients. Passive
      dynamics emerging from the morphology of the human musculoskeletal system,
      reflexes as stabilization mechanisms, modular control of movement as well as
      supra-spinal control of gait are reviewed to get insight on how these mechanisms
      can be used to explain human locomotion. 

PMID- 24111342
TI  - Validation of a passive dynamic walker model for human gait analysis.
AB  - While the dynamics and mathematics of passive dynamic walking (PDW) models have
      been extensively researched, it has not been until recently that they have been
      used for practical applications in rehabilitation and gait analysis. In this
      study, we evaluate the validity of using a two dimensional PDW for human gait
      analysis. Here, a PDW model is compared to recorded kinematic and kinetic walking
      data under normal conditions. We also study asymmetric gait by imposing a shank
      mass asymmetry and comparing it to a PDW model under the same asymmetric
      conditions. Kinematic and kinetic data for normal gait was taken from one subject
      using a motion capture system and a force plate, respectively. Gait under the
      asymmetric shank mass conditions was recorded by measuring the drifting radius of
      curvature from five participants walking blindfolded with a mass attached to
      their shank. While the PDW model lacks ankles (dorsiflexion), joint damping, and
      joint stiffness, the kinematics, kinetics, and gait asymmetry were comparable.
      Kinetic comparisons show agreement in general ground reaction force magnitude and
      profile. Kinematic results yield a good match in temporal and spatial gait
      characteristics. Asymmetric analysis of gait demonstrated that the PDW model can
      accurately predict the direction of step asymmetry. 

PMID- 24111343
TI  - Compensation of the effects of muscle fatigue on EMG-based control using fuzzy
      rules based scheme.
AB  - Estimation of the correct motion intention of the user is very important for most
      of the Electromyography (EMG) based control applications such as prosthetics,
      power-assist exoskeletons, rehabilitation and teleoperation robots. On the other
      hand, safety and long term reliability are also vital for those applications, as
      they interact with human users. By considering these requirements, many EMG-based
      control applications have been proposed and developed. However, there are still
      many challenges to be addressed in the case of EMG based control systems. One of
      the challenges that had not been considered in such EMG-based control in common
      is the muscle fatigue. The muscle fatiguing effects of the user can deteriorate
      the effectiveness of the EMG-based control in the long run, which makes the EMG
      based control to produce less accurate results. Therefore, in this study we
      attempted to develop a fuzzy rule based scheme to compensate the effects of
      muscle fatigues on EMG based control. Fuzzy rule based weights have been
      estimated based on time and frequency domain features of the EMG signals.
      Eventually, these weights have been used to modify the controller output
      according with the muscle fatigue condition in the muscles. The effectiveness of
      the proposed method has been evaluated by experiments. 

PMID- 24111344
TI  - Preparation of decellularized meniscal scaffolds using sonication treatment for
      tissue engineering.
AB  - Scaffolds play a key role in the process of regeneration and morphogenesis of
      tissue or organ. We have developed a novel sonication decellularization system to
      prepare decellularized bio-scaffolds in a short treatment time. The aim of the
      study is to investigate sonication decellularization condition that completely
      decellularize meniscus can be changed as well as to maintain the biomechanical
      parameters of scaffolds. The meniscus samples were decellularized using
      sonication treatment. The treated samples were evaluated histologically by EVG
      for cell removal, picrosirius red for content of collagen type I and III, and
      safranin-O/fast green staining for content of glycosaminoglycan, and SEM for
      observation of scaffold surface. Indentation apparatus was used to analyze the
      unconfined deformation under load of native and decellularized menisci. The load
      parameters which are stiffness, compression and residual force were not
      significantly different compare with native and sonicated scaffolds. However, the
      content of extracellular matrix and its fiber alignment changed significantly due
      to sonication treatment as observed by SEM and safranin-O/fast green staining,
      respectively. The removal of immunogenic cell components by sonication
      decellularization as well as maintain its biomechanical strength of
      decellularized scaffolds, so that it has potential to use as an implant material
      for tissue engineering of menisci. 

PMID- 24111345
TI  - Living electrodes: tissue engineering the neural interface.
AB  - Soft, cell integrated electrode coatings are proposed to address the problem of
      scar tissue encapsulation of stimulating neuroprosthetics. The aim of these
      studies was to prove the concept and feasibility of integrating a cell loaded
      hydrogel with existing electrode coating technologies. Layered conductive
      hydrogel constructs are embedded with neural cells and shown to both support cell
      growth and maintain electro activity. The safe charge injection limit of these
      electrodes was 8 times higher than conventional platinum (Pt) electrodes and the
      stiffness was four orders of magnitude lower than Pt. Future studies will
      determine the biological cues required to support stem cell differentiation from
      the electrode surface. 

PMID- 24111346
TI  - Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted
      tissue regeneration.
AB  - Scaffolds of poly(ethyl acrylate) (PEA) with interconnected cylindrical
      orthogonal pores filled with a self-assembling peptide (SAP) gel are here
      proposed as patches for infarcted tissue regeneration. These combined systems aim
      to support cell therapy and meet further requirements posed by the application:
      the three-dimensional architecture of the elastomeric scaffold is expected to
      lodge the cells of interest in the damaged zone avoiding their death or
      migration, and at the same time conduct cell behavior and give mechanical support
      if necessary; the ECM-like polypeptide gel provides a cell-friendly aqueous
      microenvironment, facilitates diffusion of nutrients and cell wastes and is
      expected to improve the distribution and viability of the seeded cells within the
      pores and stimulate angiogenesis. 

PMID- 24111347
TI  - The lifetime and attenuation properties measurements of a US/MR multimodality
      molecular probe.
AB  - In our previous studies we explored the potential of using a combined US/magnetic
      resonance (MR) multimodality contrast agent, albumin-gadolinium
      diethylenetriaminepentacetate (Gd-DTPA) MBs, to induce BBB opening and for
      distinguishing between FUS-induced BBB opening and intracerebral hemorrhage in MR
      T1-weighted contrast imaging. According to the previous study in the literature,
      1-2 um bubbles have more pronounced acoustic activity at frequencies above 10
      MHz. The present study developed a new targeted US/MR multimodality MB and the
      acoustic properties were compared with two commercial MBs, SonoVue and Targestar
      SA. The acoustic activities of these 1.15-2.78 um MBs with different shells at 10
      MHz were investigated. The feasibility of designing a new targeted US/MR
      multimodality MB was investigated. The lifetime (survival of MBs in the liquid
      suspension) and attenuation properties of lipid MBs (SonoVue and Targestar SA),
      albumin-(Gd-DTPA) MBs, and avidin-conjugated albumin (avidin-albumin)-(Gd-DTPA)
      MBs at 10 MHz were investigated with the pulse-echo substitution method. It was
      found that incorporating avidin into the albumin MBs and avidin-albumin-(Gd-DTPA)
      MBs affects the size distribution but does not affect the concentration of MBs
      produced. The avidin-albumin-shelled MBs had more significant nonlinear activity
      at 4-18 MHz (p=0.025), while the nonlinear activity of the other MBs peaked at 6
      24 MHz (p=0.003-0.044). Moreover, the incorporation of paramagnetic metal ions
      into the MB shells increased their attenuation coefficients. With regard to the
      lifetime of these agents, the attenuations of the SonoVue and Targestar SA lipid
      MBs were 87.96% and 8.74%, respectively, while those of albumin MBs, avidin
      albumin MBs, albumin-(Gd-DTPA) MBs, and avidin-albumin-(Gd-DTPA) MBs were 49.52%,
      41.38%, 74.69%, and 100%, respectively. Avidin conjugation decreased the lifetime
      of the albumin MBs, but not that of the lipid MBs. The incorporation of
      paramagnetic metal ions into the shells of albumin MBs did not decrease the
      lifetime. 

PMID- 24111348
TI  - Construction of a chondrocyte cell sheet using temperature-responsive poly(N
      isopropylacrylamide)-co-acrylamide.
AB  - In this study, a novel temperature-responsive poly(N-isopropylacrylamide)-co
      acrylamide was used to prepare a chondrocyte cell sheet. Chondrocytes were
      isolated from human articular cartilage and plated on the copolymer film grafted
      tissue culture plates. The cell attachment on the copolymer film was shown to be
      similar to that of the ungrafted surface. To harvest a cell sheet, the incubation
      temperature was reduced to 10 degrees C for 30 minutes to allow the polymer chain
      to fully extend, changing the copolymer's phase from hydrophobicity to
      hydrophilicity. Additional incubation at 20 degrees C for 60 minutes was
      necessary to activate the cellular metabolism required for cytoskeletal
      organization and cell detachment. A complete cell sheet recovery was achieved
      when a PVDF membrane was used as a cell sheet carrier. Unfortunately, the
      shrinkage of the cell sheet was observed. Nonetheless, the harvested cell sheet
      was shown to be viable and healthy. 

PMID- 24111349
TI  - Cell attachment and viability on micro-arc-oxidation (MAO) microwave/hydrothermal
      treated titanium surface.
AB  - The purpose of this study is to investigate the cell attachment and viability on
      the micro-arc oxidization (MAO) microwave/hydrothermal treated titanium surfaces.
      The MAO samples were microwave irradiated in vessels containing 50 mL of double
      distilled water for 30 minutes (MWDD). The immersion solution consisted of 0.05
      mM calcium hydroxide and 0.03 mM ammonium dihydrogen phosphate (MWCP), and same
      solution with the pH value adjusted to 9.6 (MWCP9.6) were compared. The
      hydrothermal (HT) samples were conducted under DD water at 250 degrees C for 3
      hr. The cell viability (WST assay) results show that there was no significant
      different on the cell viability at 4 hrs. After cultured for 1 day, the cell
      viability of MG63 cells on the samples from high to low is HT = MWDD = MWCP >
      MWCP9.6 > MAO. No significant different was found on the cell number between
      groups. However, the percentages of spreading cells to total adherent cells are
      higher on the MWDD, MWCP, and MWCP9.6 groups (75.7%, 69.9%, 69.4%, respectively),
      when compare to MAO and HT groups (48.4% and 41.5%). These results demonstrate
      that increased cell spreading on a MW groups with submicro-to- nano scale calcium
      phosphates on titania produced by microwave/hydrothermal process.

PMID- 24111350
TI  - u-MCHC: a predictive framework for ubiquitous management of exacerbations in
      chronic diseases.
AB  - Exacerbations are crucial events in chronic diseases that require continuous
      management. Knowledge of the exacerbation risk enhances patient's quality of life
      and enables self-management and self-organizing of unscheduled doctor visits
      and/or hospitalization. This paper proposes a new framework for ubiquitous
      management of chronic diseases named u-MCHC. The proposed framework incorporates
      monitoring, decision-making, notification and management processes in order to
      deliver personalized therapeutical options and services. The delivery of services
      is realized by means of Next Generation Service Delivery Platform (NG-SDP). A
      prototype implementation of u-MCHC and its performance is demonstrated in a real
      world case for Chronic Obstructive Pulmonary Disease (COPD). 

PMID- 24111351
TI  - Cardiovascular disease risk assessment innovative approaches developed in
      HeartCycle project.
AB  - Two innovative CVD event risk assessment strategies were developed in the scope
      of HeartCycle project: i) combination of individual risk assessment tools; ii)
      personalization of risk assessment based on grouping of patients. These
      approaches aimed to defeat some of the major limitations of the tools currently
      applied in the daily clinical practice, namely to: i) improve the risk prediction
      performance when comparing it to the one achieved by the individual current risk
      assessment tools; ii) consider the available knowledge provided by other risk
      assessment tools; iii) cope with missing risk factors; iv) incorporate additional
      clinical knowledge. Two different real patients' datasets were applied to
      validate the developed strategies: i) Santa Cruz Hospital, Portugal, N=460 ACS
      NSTEMI1 patients; ii) Leiria Pombal Hospital Centre, Portugal, N=99 ACS-NSTEMI.
      Based on the gathered results, we propose a new strategy in order to improve
      patients' stratification.

PMID- 24111352
TI  - HeartCycle: advanced sensors for telehealth applications.
AB  - Current treatment of Cardiovascular Disease (CVD)--the most frequent cause of
      hospitalization for people over 65--involves changes of diet and lifestyle,
      requiring in addition physical exercise to support these. Nowadays, patients
      receive sporadic feedback at doctor visits, or later on, when facing symptoms.
      The HeartCycle project aimed at providing 1) daily monitoring, 2) close follow
      up, 3) help on treatment routine and 4) decreasing non-compliance to treatment
      regimes. The present paper illustrates a new toolbox of advanced sensors
      developed within the HeartCycle project. Ongoing clinical studies support these
      developments.

PMID- 24111353
TI  - HeartCycle: user interaction and patient education.
AB  - Cardiovascular Diseases are the most prevalent and serious chronic conditions
      existing nowadays. They are the primary cause of death in the world and generate
      enormous expenditures to the health systems. Tele-monitoring and personal health
      systems have proven to be good options for tackling this situation; however they
      are still lacking many functionalities. It is necessary to find solutions that
      allow health professionals to follow up patients more closely and efficiently,
      while reducing the non-adherence of patients to the treatment regime. HeartCycle
      research project (partially funded by the European Commission) has developed a
      personal health system for cardiovascular diseases management with the aim to
      address this problem. This paper describes the Patient Loop of this solution,
      including the different components, the adopted user interaction, and the
      implemented patients' education and coaching strategy. 

PMID- 24111354
TI  - HeartCycle: from insights to clinically evaluated ICT solutions for Telehealth.
AB  - HeartCycle is a large European Integrated Project (IP) and develops technologies
      and services for Telehealth, which is to remotely monitor and manage patients at
      home and motivate them to be compliant to treatment regimens and to a beneficial
      lifestyle. Telehealth allows healthcare professionals to better control the
      progress of the therapy, detect upcoming adverse events early and react in time
      with personalized care plan adjustments, leading to prevent relapses, stabilizing
      the patient and avoid costly hospitalizations. 

PMID- 24111355
TI  - Heart Cycle: facilitating the deployment of advanced care processes.
AB  - Current trends in health management improvement demand the standardization of
      care protocols to achieve better quality and efficiency. The use of Clinical
      Pathways is an emerging solution for that problem. However, current Clinical
      Pathways are big manuals written in natural language and highly affected by human
      subjectivity. These problems make their deployment and dissemination extremely
      difficult in real practice environments. Furthermore, the intrinsic difficulties
      for the design of formal Clinical Pathways requires new specific design tools to
      help making them relly useful and cost-effective. Process Mining techniques can
      help to automatically infer processes definition from execution samples and,
      thus, support the automatization of the standardization and continuous control of
      healthcare processes. This way, they can become a relevant helping tool for
      clinical experts and healthcare systems for reducing variability in clinical
      practice and better understand the performance of the system. 

PMID- 24111356
TI  - Analysis of endocardial acceleration during intraoperative optimization of
      cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is the therapy of choice for selected
      patients suffering from drug-refractory congestive heart failure and presenting
      an interventricular desynchronization. CRT is delivered by an implantable
      biventricular pacemaker, which stimulates the right atrium and both ventricles at
      specific timings. The optimization and personalization of this therapy requires
      to quantify both the electrical and the mechanical cardiac functions during the
      intraoperative and postoperative phases. The objective of this paper is to
      evaluate the feasibility of the calculation of features extracted from
      endocardial acceleration (EA) signals and the potential utility of these features
      for the intraoperative optimization of CRT. Endocardial intraoperative data from
      one patient are analyzed for 33 different pacing configurations, including
      changes in the atrio-ventricular and inter-ventricular delays and different
      ventricular stimulation sites. The main EA features are extracted for each pacing
      configuration and analyzed so as to estimate the intra-configuration and inter
      configuration variability. Results show the feasibility of the proposed approach
      and suggest the potential utility of EA for intraoperative monitoring of the
      cardiac function and defining optimal, adaptive pacing configurations. 

PMID- 24111357
TI  - Seismocardiography: past, present and future.
AB  - This paper presents an overview of seismocardiography (SCG) as a noninvasive
      cardiology method. The paper represents a brief historical background to the SCG,
      an assessment of the technology at present, and an evaluation of the challenges
      we must address. These challenges include the development and clarification of
      definitions, standards, and annotations. 

PMID- 24111358
TI  - Local ballistocardiographic spectrum studies from signals obtained from limbs and
      carotid artery with an EMFi sensor induced with a tilt table.
AB  - The purpose of this work is to study the effect of a tilt table test procedure on
      ballistocardiographic (BCG) signal by using Electromechanical Film (EMFi) strip
      sensors. The ECG, BCG, carotid pulse (CP) from the neck near the carotid artery
      and ankle pulse signals were recorded from 7 persons. The spectral components of
      the recordings during the tilt table test were studied concentrating mainly on
      heart induced pulsatile signals propagating along the artery to the periphery.
      The properties of BCG pulse signal changed due to the tilt test in spectral
      domain. Blood pressure (BP) values and shape of the pulse changed due to the tilt
      test. According to this study, local BCG measurements with EMFi sensor strips
      combined with a tilt test can be used as a very simple non-invasive method in
      hemodynamic studies. 

PMID- 24111359
TI  - 3D-ballistocardiography in microgravity: comparison with ground based recordings.
AB  - 3D-Ballistocardiograms ECG and Impedancecardiograms (ICG) were recorded on 5
      healthy volunteers participating to the European Space Agency (ESA) 57(th)
      parabolic flights campaigns. Comparisons are made between the baseline recordings
      performed on the ground and the recordings made during the microgravity phases of
      a parabolic flight. The spatial curves of the displacement, velocity and
      acceleration vectors, instead of their individual components are used to compute
      the magnitude of the force vector, kinetic energy and work during the cardiac
      cycle. Our hypothesis is that the 3D-BCG provides parameters correlated with the
      timings of ejection (PEP, LVET). Although our subject population is limited
      (N=5), this is the first study of BCG to be performed with N>1. Our results
      suggest that microgravity decrease the complexity of the 3D displacement curve
      and that peaks in curvature are consistently present in microgravity and on the
      ground. However they do not seem to be perfectly related to the classical cardiac
      ejection timings from ICG. 

PMID- 24111360
TI  - Beat-to-beat estimation of LVET and QS2 indices of cardiac mechanics from
      wearable seismocardiography in ambulant subjects.
AB  - Seismocardiogram (SCG) is the measure of the minute vibrations produced by the
      beating heart. We previously demonstrated that SCG, ECG and respiration could be
      recorded over the 24 h during spontaneous behavior by a smart garment, the MagIC
      SCG system. In the present case study we explored the feasibility of a beat-to
      beat estimation of two indices of heart contractility, the Left Ventricular
      Ejection Time (LVET) and the electromechanical systole (QS2) from SCG and ECG
      recordings obtained by the MagIC-SCG device in one subject. We considered data
      collected during outdoor spontaneous behavior (while sitting in the metro and in
      the office) and in a laboratory setting (in supine and sitting posture, and
      during recovery after 100 W and 140 W cycling). LVET was estimated from SCG as
      the time interval between the opening and closure of the aortic valve, QS2 as the
      time interval between the Q wave of the ECG and the closure of the aortic valve.
      In every condition, LVET and QS2 could be estimated on a beat-to-beat basis from
      the SCG collected by the smart garment. LVET and QS2 are characterized by
      important beat-to-beat fluctuations, with standard deviations in the same order
      of magnitude of RR Interval. In all settings, spectral profiles are different for
      LVET, QS2 and RR Interval. This suggests that the biological mechanisms impinging
      on the heart exert a differentiated influence on the variability of each of these
      three indices.

PMID- 24111361
TI  - Comparative analysis of two systems for unobtrusive heart signal acquisition and
      characterization.
AB  - In this paper we describe and compared method of heart rate estimation from
      cardiac signal acquired with EMFIT, FMCW Doppler radar and Finapres based
      technology, in the same context, and briefly investigated their similarities and
      differences. Study of processing of acquired cardiac signal for accurate peak
      detection using Wavelet Transform is also described. The results suggest good
      reliability of the two implemented unobtrusive systems for heart rate estimation.

PMID- 24111362
TI  - A socialization intervention in remote health coaching for older adults in the
      home.
AB  - Previous studies have shown that social ties enhance both physical and mental
      health, and that social isolation has been linked to increased cognitive decline.
      As part of our cognitive training platform, we created a socialization
      intervention to address these issues. The intervention is designed to improve
      social contact time of older adults with remote family members and friends using
      a variety of technologies, including Web cameras, Skype software, email and
      phone. We used usability testing, surveys, interviews and system usage monitoring
      to develop design guidance for socialization protocols that were appropriate for
      older adults living independently in their homes. Our early results with this
      intervention show increased number of social contacts, total communication time
      (we measure email, phone, and Skype usage) and significant participant
      satisfaction with the intervention. 

PMID- 24111363
TI  - Detecting degeneration: monitoring cognitive health in independent elders.
AB  - Australia has an ever increasing ageing population due to advances in healthcare
      and post-war booms in fertility. Estimations that over 22% of the population will
      be aged 65+ in 2050 provide a strong incentive to develop innovative assistive
      technologies to support elderly people to live safely at home longer. Extended
      independent living can improve quality of life for elders and their families and
      reduce costs associated with health and aged care. There is however, the need to
      monitor the elderly resident's safety, physical health and brain function. The
      Smarter Safer Homes project aims to develop a platform to facilitate independent
      living. The platform will aggregate sensor information at environmental,
      cognitive, physical, and physiological levels, allowing changes and trends in
      activities of daily living to be monitored. Such monitoring could potentially
      predict decline of brain function. Here we present how data derived from a sensor
      based in-home monitoring system may be able to be used to provide a measure of
      neurological health. This measure could then facilitate tailoring of the home to
      meet the resident's changing needs, or to determine when a move to residential
      care is required. 

PMID- 24111364
TI  - Step Training System: an ICT solution to measure and reduce fall risk in older
      adults.
AB  - Falls in older adults are a significant public heath issue with over 1/3
      community-dwelling people aged 65 and over falling each year, many of them
      multiple times. We have developed and evaluated a set top box PC solution for
      delivering both fall risk assessment and fall risk reduction programs into the
      home. Preliminary field tests show that older adults engage with the system but
      that barriers to maintained use of the system do exist. 

PMID- 24111365
TI  - Self directed home based electrical muscle stimulation training improves exercise
      tolerance and strength in healthy elderly.
AB  - Advancing age is associated with a gradual decline in muscle strength, exercise
      tolerance and subsequent capacity for activities of daily living. It is important
      that we develop effective strategies to halt this process of gradual decline in
      order to enhance functional ability and capacity for independent living. To
      achieve this, we must overcome the challenge of sustaining ongoing engagement in
      physical exercise programmes in the sedentary elderly population, particularly
      those who experience barriers to exercise participation. Recent developments in
      electrical muscle stimulation technology could provide a potential solution. In
      this pilot case-control study we investigated the effects of a self-directed home
      based programme of electrical muscle stimulation training on muscle strength and
      exercise tolerance in a group of 16 healthy elderly volunteers (10f, 6m). Study
      participants completed 30 separate 1-hour electrical muscle stimulation sessions
      at home over a 6-week period. We observed significant improvements in quadriceps
      muscle strength and 6-minute walk distance, suggesting that this form of
      electrical muscle stimulation training has promise as an exercise modality in the
      elderly population. 

PMID- 24111366
TI  - Everyday technologies across the continuum of dementia care.
AB  - The nomenclature for Alzheimer disease has recently been revised to include
      preclinical and mild cognitive impairment stages, along with dementia. These new
      stages provide an opportunity for primary, secondary, and tertiary prevention
      strategies. Everyday technologies have a key role to play in all of these
      strategies as well as caregiver education and support. Primary prevention
      strategies include development of cognitive reserve through computerized brain
      fitness programs. Secondary prevention involves the development of routines,
      including mobile device based strategies to compensate for memory deficits.
      Telemedicine approaches can facility tertiary invention, and communication and
      internet resources aid in caregiver support and education. 

PMID- 24111367
TI  - Determination of Activities of Daily Living of independent living older people
      using environmentally placed sensors.
AB  - The rapid increase in the ageing population of most developed countries is
      presenting significant challenges to policymakers of public healthcare. To
      address this problem, we propose a Smarter Safer Home solution that enables
      ageing Australians to live independently longer in their own homes. The primary
      aim of our approach is to enhance the Quality of Life (QoL) of aged citizens and
      the Family Quality of Life (FQoL) for the adult children supporting their aged
      parents. To achieve this, we use environmentally placed sensors for non-intrusive
      monitoring of human behaviour. The various sensors will detect and gather
      activity and ambience data which will be fused through specific decision support
      algorithms to extract Activities of Daily Living (ADLs). Subsequently, these
      estimated ADLs would be correlated with reported and recorded health events to
      predicate health decline or critical health situations from the changes in ADLs. 

PMID- 24111368
TI  - Multiple kernel learning for brain-computer interfacing.
AB  - Combining information from different sources is a common way to improve
      classification accuracy in Brain-Computer Interfacing (BCI). For instance, in
      small sample settings it is useful to integrate data from other subjects or
      sessions in order to improve the estimation quality of the spatial filters or the
      classifier. Since data from different subjects may show large variability, it is
      crucial to weight the contributions according to importance. Many multi-subject
      learning algorithms determine the optimal weighting in a separate step by using
      heuristics, however, without ensuring that the selected weights are optimal with
      respect to classification. In this work we apply Multiple Kernel Learning (MKL)
      to this problem. MKL has been widely used for feature fusion in computer vision
      and allows to simultaneously learn the classifier and the optimal weighting. We
      compare the MKL method to two baseline approaches and investigate the reasons for
      performance improvement. 

PMID- 24111369
TI  - Adaptive power projection method for accumulative EEG classification.
AB  - For the dynamic classification of motor imagery mind states in the brain-computer
      interface (BCI), we propose a power projection based feature extraction method to
      classify the electroencephalogram (EEG) signals by combining information
      accumulative posterior Bayesian approach. This method improves the classification
      accuracy by maximizing the average projection energy difference of the two types
      of signals. The experimental results on two BCI competition datasets show that
      the classification accuracy is about 90%. The results of the classification
      accuracy and mutual information demonstrate the effectiveness of this method. 

PMID- 24111370
TI  - Extending motor imagery by speech imagery for brain-computer interface.
AB  - An electroencephalogram (EEG)-based brain computer interface (BCI) is a novel
      tool that translates brain intentions into control signals. As the operational
      dimensions of motor imagery are limited, we describe in this paper an extension
      of its capability by including speech imagery. Our new system was tested with the
      help of subjects, whose native language is Chinese. The tests were divided into
      two steps. The first step was speech imagery; consequently motor imagery and
      speech imagery were merged in the second step. Feature vectors of EEG signals
      were extracted from both common spatial patterns (CSP) and cross-correlation
      functions; then these vectors were classified by a support vector machine (SVM).
      The distinguishing accuracies of two intentions were found to be between 79.33%
      and 88.26%. This result shows that the capability of BCI for motor imagery can be
      extended by combining motor imagery and speech imagery. 

PMID- 24111371
TI  - Sequential selection of window length for improved SSVEP-based BCI
      classification.
AB  - Brain-computer interfaces (BCI) utilizing steady-state visually evoked potentials
      (SSVEP) recorded by electroencephalography (EEG) have exciting potential to
      enable new systems for disabled individuals and novel controls for robotic and
      computer systems. To interact with SSVEP-based BCIs, users attend to visual
      stimuli modulated at predetermined frequencies. A key problem for SSVEP-based
      BCIs is to classify which modulation frequency the user is attending, for which
      there is an inherent trade-off between speed and accuracy. As SSVEP signals vary
      with time and stimulation frequency, a fixed-length data window does not
      necessarily optimize this trade-off. We propose a strategy, developed from
      sequential analysis, to vary the window-length used for classification. Our
      proposed technique adapts to the data, continuing to collect data until it is
      confident enough to make a classification decision. Our strategy was compared to
      a fixed window-length method using a simple experiment involving five frequencies
      presented individually to three participants. Using a canonical correlation
      analysis classifier to compare the proposed variable-length scheme to a standard
      fixed-length scheme, the variable-length approach improved the classifier
      information transfer rate by an average of 43%. 

PMID- 24111372
TI  - An improved P300 extraction using ICA-R for P300-BCI speller.
AB  - In this study, a new P300 extraction method is investigated by using a form of
      constrained independent component analysis (cICA) algorithm called one-unit ICA
      with-reference (ICA-R) which extracts the P300 signal based on its temporal
      information. The main advantage of this method compared to the existing ICA-based
      method is that the desired P300 signal is extracted directly without requiring
      partial or full signal decomposition and any post-processing on the outcome of
      the ICA before the P300 signal can be obtained. Since only one IC is extracted,
      the method is computationally more efficient for real-time P300 BCI applications.
      In our study, when tested on the BCI competition 2003 dataset IIb, the current
      state-of-the-art performance is maintained by using the one-unit ICA-R. Besides
      that, the ability of the method to visualize P300 signals at the single-trial
      level also suggests it has potential applications in other types of ERP studies. 

PMID- 24111373
TI  - Feature relevance analysis supporting automatic motor imagery discrimination in
      EEG based BCI systems.
AB  - Recently, there have been many efforts to develop Brain Computer Interface (BCI)
      systems, allowing identifying and discriminating brain activity, as well as,
      support the control of external devices, and to understand cognitive behaviors.
      In this work, a feature relevance analysis approach based on an eigen
      decomposition method is proposed to support automatic Motor Imagery (MI)
      discrimination in electroencephalography signals for BCI systems. We select a set
      of features representing the best as possible the studied process. For such
      purpose, a variability study is performed based on traditional Principal
      Component Analysis. EEG signals modelling is carried out by feature estimation of
      three frequency-based and one time-based. Our approach provides testing over a
      well-known MI dataset. Attained results show that presented algorithm can be used
      as tool to support discrimination of MI brain activity, obtaining acceptable
      results in comparison to state of the art approaches. 

PMID- 24111374
TI  - Tracking progression of patient state of health in critical care using inferred
      shared dynamics in physiological time series.
AB  - Physiologic systems generate complex dynamics in their output signals that
      reflect the changing state of the underlying control systems. In this work, we
      used a switching vector autoregressive (switching VAR) framework to
      systematically learn and identify a collection of vital sign dynamics, which can
      possibly be recurrent within the same patient and shared across the entire
      cohort. We show that these dynamical behaviors can be used to characterize and
      elucidate the progression of patients' states of health over time. Using the mean
      arterial blood pressure time series of 337 ICU patients during the first 24 hours
      of their ICU stays, we demonstrated that the learned dynamics from as early as
      the first 8 hours of patients' ICU stays can achieve similar hospital mortality
      prediction performance as the well-known SAPS-I acuity scores, suggesting that
      the discovered latent dynamics structure may yield more timely insights into the
      progression of a patient's state of health than the traditional snapshot-based
      acuity scores. 

PMID- 24111375
TI  - Novel heuristic search for ventricular arrhythmia detection using normalized cut
      clustering.
AB  - Processing of the long-term ECG Holter recordings for accurate arrhythmia
      detection is a problem that has been addressed in several approaches. However,
      there is not an outright method for heartbeat classification able to handle
      problems such as the large amount of data and highly unbalanced classes. This
      work introduces a heuristic-search-based clustering to discriminate among
      ventricular cardiac arrhythmias in Holter recordings. The proposed method is
      posed under the normalized cut criterion, which iteratively seeks for the nodes
      to be grouped into the same cluster. Searching procedure is carried out in
      accordance to the introduced maximum similarity value. Since our approach is
      unsupervised, a procedure for setting the initial algorithm parameters is
      proposed by fixing the initial nodes using a kernel density estimator. Results
      are obtained from MIT/BIH arrhythmia database providing heartbeat labelling. As a
      result, proposed heuristic-search-based clustering shows an adequate performance,
      even in the presence of strong unbalanced classes. 

PMID- 24111376
TI  - Discovering hidden relationships in physiological signals for prediction of
      Periventricular Leukomalacia.
AB  - This paper is concerned with predicting the occurrence of Periventricular
      Leukomalacia (PVL) using vital data which are collected over a period of twelve
      hours after neonatal cardiac surgery. The vital data contain heart rate (HR),
      mean arterial pressure (MAP), right atrium pressure (RAP), and oxygen saturation
      (SpO2). Various features are extracted from the data and are then ranked so that
      an optimal subset of features that have the highest discriminative capabilities
      can be selected. A decision tree (DT) is then developed for the vital data in
      order to identify the most important vital measurements. The DT result shows that
      high amplitude 20 minutes variations and low sample entropy in the data is an
      important factor for prediction of PVL. Low sample entropy represents lack of
      variability in hemodynamic measurement, and constant blood pressure with small
      fluctuations is an important indicator of PVL occurrence. Finally, using the
      different time frames of the collected data, we show that the first six hours of
      data contain sufficient information for PVL occurrence prediction. 

PMID- 24111377
TI  - Clinical validation of the CHRONIOUS wearable system in patients with chronic
      disease.
AB  - The CHRONIOUS system defines a powerful and easy to use framework which has been
      designed to provide services to clinicians and their patients suffering from
      chronic diseases. The system is composed of a wearable shirt that integrate
      several body sensors, a portable smart device and a central sub-system that is
      responsible for the long term storage of the collected patient's data. A multi
      parametric expert system is developed for the analysis of the collected data
      using intelligent algorithms and complex techniques. Apart for the vital signals,
      dietary habits, drug intake, activity data, environmental and biochemical
      parameters are recorded. The CHRONIOUS platform is validated through clinical
      trials in several medical centers and patient's home environments recruiting
      patients suffering from Chronic Obstructive pulmonary disease (COPD) and Chronic
      Kidney Disease (CKD) diseases. The clinical trials contribute in improving the
      system's accuracy, while Pulmonologists and Nephrologists experts utilized the
      CHRONIOUS platform to evaluate its efficiency and performance. The results of the
      utilization of the system were very encouraging. The CHRONIOUS system has been
      proven to be a well-validated real-time patient monitoring and supervision
      platform, providing a useful tool for the clinician and the patient that would
      contribute to the more effective management of chronic diseases. 

PMID- 24111378
TI  - Detection of sleep apnea events via tracking nonlinear dynamic cardio-respiratory
      coupling from electrocardiogram signals.
AB  - Obstructive sleep apnea (OSA) is a common sleep disorder that causes increasing
      risk of mortality and affects quality of life of approximately 6.62% of the total
      US population. Timely detection of sleep apnea events is vital for the treatment
      of OSA. In this paper, we present a novel approach based on extracting the
      quantifiers of nonlinear dynamic cardio-respiratory coupling from
      electrocardiogram (ECG) signals to detect sleep apnea events. The quantifiers of
      the cardio-respiratory dynamic coupling were extracted based on recurrence
      quantification analysis (RQA), and a battery of statistical data mining
      techniques were to enhance OSA detection accuracy. This approach would lead to a
      cost-effective and convenient means for screening of OSA, compared to traditional
      polysomnography (PSG) methods. The results of tests conducted using data from
      PhysioNets Sleep Apnea database suggest excellent quality of the OSA detection
      based on a thorough comparison of multiple models, using model selection criteria
      of validation data: Sensitivity (91.93%), Specificity (85.84%), Misclassification
      (11.94%) and Lift (2.7). 

PMID- 24111379
TI  - A variational nonparametric Bayesian approach for inferring rat hippocampal
      population codes.
AB  - Rodent hippocampal population codes represent important spatial information of
      the environment during navigation. Several computational methods have been
      developed to uncover the neural representation of spatial topology embedded in
      rodent hippocampal ensemble spike activity. Here we extend our previous work and
      propose a nonparametric Bayesian approach to infer rat hippocampal population
      codes. Specifically, we develop an infinite hidden Markov model (iHMM) and
      variational Bayes (VB) inference method to analyze rat hippocampal ensemble spike
      activity. We demonstrate the effectiveness of our approach using an open field
      navigation example and discuss the significance/implications of our results. 

PMID- 24111380
TI  - Estimating inputs and an internal neuronal parameter from a single spike train.
AB  - Because neurons are integrating input signals and translating them into timed
      output spikes, examining spike timing may reveal information about inputs, such
      as population activities of excitatory and inhibitory presynaptic neurons. Here
      we construct a state-space method for estimating not only such extrinsic
      parameters, but also an intrinsic neuronal parameter such as the membrane time
      constant from a single spike train. 

PMID- 24111381
TI  - A stabilized dual Kalman filter for adaptive tracking of brain-computer interface
      decoding parameters.
AB  - Neural prosthetics are a promising technology for alleviating paralysis by
      actuating devices directly from the intention to move. Typical implementations of
      these devices require a calibration session to define decoding parameters that
      map recorded neural activity into movement of the device. However, a major factor
      limiting the clinical deployment of this technology is stability: with fixed
      decoding parameters, control of the prosthetic device has been shown to degrade
      over time. Here we apply a dual estimation procedure to adaptively capture
      changes in decoding parameters. In simulation, we find that our stabilized dual
      Kalman filter can run autonomously for hundreds of thousands of trials with
      little change in performance. Further, when we apply our algorithm off-line to
      estimate arm trajectories from neural data recorded over five consecutive days,
      we find that it outperforms a static Kalman filter, even when it is re-calibrated
      at the beginning of each day. 

PMID- 24111382
TI  - Learning outcome-discriminative dynamics in multivariate physiological cohort
      time series.
AB  - Model identification for physiological systems is complicated by changes between
      operating regimes and measurement artifacts. We present a solution to these
      problems by assuming that a cohort of physiological time series is generated by
      switching among a finite collection of physiologically-constrained dynamical
      models and artifactual segments. We model the resulting time series using the
      switching linear dynamical systems (SLDS) framework, and present a novel learning
      algorithm for the class of SLDS, with the objective of identifying time series
      dynamics that are predictive of physiological regimes or outcomes of interest. We
      present exploratory results based on a simulation study and a physiological
      classification example of decoding postural changes from heart rate and blood
      pressure. We demonstrate a significant improvement in classification over methods
      based on feature learning via expectation maximization. The proposed learning
      algorithm is general, and can be extended to other applications involving state
      space formulations. 

PMID- 24111383
TI  - Real-time segmentation and tracking of brain metabolic state in ICU EEG
      recordings of burst suppression.
AB  - We provide a method for estimating brain metabolic state based on a reduced-order
      model of EEG burst suppression. The model, derived from previously suggested
      biophysical mechanisms of burst suppression, describes important
      electrophysiological features and provides a direct link to cerebral metabolic
      rate. We design and fit the estimation method from EEG recordings of burst
      suppression from a neurological intensive care unit and test it on real and
      synthetic data. 

PMID- 24111384
TI  - Band specific changes in thalamocortical synchrony in field potentials after
      cardiac arrest induced global hypoxia.
AB  - Cardiac Arrest (CA) leads to a global hypoxic-ischemic injury in the brain
      leading to a poor neurological outcome. Understanding the mechanisms of
      functional disruption in various regions of the brain may be essential for the
      development of improved diagnostic and therapeutic solutions. Using controlled
      laboratory experiment with animal models of CA, our primary focus here is on
      understanding the functional changes in the thalamus and the cortex, associated
      with the injury and acute recovery upon resuscitation. Specifically, to study the
      changes in thalamocortical synchrony through these periods, we acquired local
      field potentials (LFPs) from the ventroposterior lateral (VPL) nucleus of the
      thalamus and the forelimb somatosensory cortex (S1FL) in rats after asphyxial CA.
      Band-specific relative Hilbert phases were used to analyze synchrony between the
      LFPs. We observed that the CA induced global ischemia changes the local phase
      relationships by introducing a phase-lag in both the thalamus and the cortex,
      while the synchrony between the two regions is nearly completely lost after CA. 

PMID- 24111385
TI  - Automated measurement of cerebral cortical thickness based on fuzzy membership
      map derived from MR images for evaluation of Alzheimer's disease.
AB  - We have proposed an automated method for three-dimensional (3D) measurement of
      cerebral cortical thicknesses based on fuzzy membership maps derived from
      magnetic resonance (MR) images for evaluation of Alzheimer's disease (AD). The
      cerebral cortical thickness was three-dimensionally measured on each cortical
      surface voxel by using a localized gradient vector trajectory in a fuzzy
      membership map. The proposed method could be useful for the 3D measurement of the
      cerebral cortical thickness on individual cortical surface voxels as an atrophy
      feature in AD. 

PMID- 24111386
TI  - A pruned ensemble classifier for effective breast thermogram analysis.
AB  - Thermal infrared imaging has been shown to be useful for diagnosing breast
      cancer, since it is able to detect small tumors and hence can lead to earlier
      diagnosis. In this paper, we present a computer-aided diagnosis approach for
      analysing breast thermograms. We extract image features that describe bilateral
      differences of the breast regions in the thermogram, and then feed these features
      to an ensemble classifier. For the classification, we present an extension to the
      Under-Sampling Balanced Ensemble (USBE) algorithm. USBE addresses the problem of
      imbalanced class distribution that is common in medical decision making by
      training different classifiers on different subspaces, where each subspace is
      created so as to resemble a balanced classification problem. To combine the
      individual classifiers, we use a neural fuser based on discriminants and apply a
      classifier selection procedure based on a pairwise double-fault diversity measure
      to discard irrelevant and similar classifiers. We demonstrate that our approach
      works well, and that it statistically outperforms various other ensemble
      approaches including the original USBE algorithm. 

PMID- 24111387
TI  - An automatic bone segmentation method based on anatomical structure for the knee
      joint in MDCT image.
AB  - The purpose of this study is to propose an automatic segmentation about each bone
      (the femur, the tibia, the patellar, and fibular) of the knee in MDCT image. The
      proposed method was applied for six patients (Age 33 +/- 13, four males/tew
      females). The proposed method segmented the knee joint into each bone by using
      anatomical structure for the knee joint. The experiments calculate matching rate
      of the manual and the proposed method for evaluating it. As a result, The
      matching rate of the femur, the tibia, the patellar, and fibula were 95.84 +/-
      0.57%, 94.12 +/- 1.01%, 94.49 +/- 0.83%, 86.37 +/- 4.28%, respectively. This
      study concluded that the proposed method is enough to segment the knee bones.

PMID- 24111388
TI  - EEG epileptic seizures separation with multivariate empirical mode decomposition
      for diagnostic purposes.
AB  - We present a successful application of a soft computing approach based on the
      multivariate empirical mode decomposition (MEMD) method to EEG epileptic seizures
      separation. The results of the automatic multivatiate intrinsic mode functions
      (IMF) clustering allowed us to separate the seizure related spikes and sharp
      waves. The results of the proposed method have been compared with classical blind
      separation approach based on ICA, which failed to identify the non-linear and non
      stationary signals related to the brain seizures. The proposed method supports
      epileptic seizure diagnostic methods. 

PMID- 24111389
TI  - An EEG diagnosis system for quasi brain death based on complexity and energy
      analyses.
AB  - Electroencephalogram (EEG) is often used in confirmatory test for brain death
      determination in clinical practice. Because the EEG measuring and monitoring is
      relatively safe and reliable for deep comatose patients, it is believed to be
      valuable for reducing the risk of diagnosis or prevent mistaken diagnosis of
      brain death. In this paper, we present EEG complexity analysis and EEG energy
      analyses for the EEG acquisition of 35 adult patients. In EEG complexity
      analysis, we firstly report statistically significant differences of quantitative
      statistics in this clinical study. Next, for the patient-wise case study, we
      develop a dynamical calculating entropy method to monitor the symptom change of
      patients. In EEG energy analysis, we firstly accumulate the EEG energy from the
      extracted components that are related to the brain activities. Then, we evaluate
      the energy differences between deep comatose patients and brain death. The
      empirical results reported in this paper suggest some promising directions and
      valuable clues for clinical practice. 

PMID- 24111390
TI  - Fuzzy connectedness image segmentation for newborn brain extraction in MR images.
AB  - Newborn's brain has a various shape, and easily changes with not only brain
      developing and cerebral diseases. Although the brain segmentation in MR images is
      an effective way to quantify the brain shape and size, there are few studies in
      neonatal brain MR image analysis. This paper introduces a novel method based on
      fuzzy connectedness (FC) with fuzzy object model (FOM). FOM is built from a
      training dataset, and gives fuzzy degree belonging to parenchyma with respect to
      location and intensity. FC is calculated from object affinity and homogeneous
      affinity, and the object affinity is given by the FOM. The method first segments
      the white matter, and then segments the surrounding cortex. The propose method
      has been applied to 10 newborn subjects whose revised age was between -1 month
      and +2 month. Leave-on-out cross-validation (LOOCV) was conducted, and the mean
      false-positive volume fraction was 1.33%, the mean false-negative volume fraction
      was 2.90%, and geometric-mean was 1.42%. 

PMID- 24111391
TI  - Retina image analysis and ocular telehealth: the Oak Ridge National Laboratory
      Hamilton Eye Institute case study.
AB  - Automated retina image analysis has reached a high level of maturity in recent
      years, and thus the question of how validation is performed in these systems is
      beginning to grow in importance. One application of retina image analysis is in
      telemedicine, where an automated system could enable the automated detection of
      diabetic retinopathy and other eye diseases as a low-cost method for broad-based
      screening. In this work, we discuss our experiences in developing a telemedical
      network for retina image analysis, including our progression from a manual
      diagnosis network to a more fully automated one. We pay special attention to how
      validations of our algorithm steps are performed, both using data from the
      telemedicine network and other public databases. 

PMID- 24111392
TI  - Multimedia data mining for automatic diabetic retinopathy screening.
AB  - This paper presents TeleOphta, an automatic system for screening diabetic
      retinopathy in teleophthalmology networks. Its goal is to reduce the burden on
      ophthalmologists by automatically detecting non referable examination records,
      i.e. examination records presenting no image quality problems and no pathological
      signs related to diabetic retinopathy or any other retinal pathology. TeleOphta
      is an attempt to put into practice years of algorithmic developments from our
      groups. It combines image quality metrics, specific lesion detectors and a
      generic pathological pattern miner to process the visual content of eye fundus
      photographs. This visual information is further combined with contextual data in
      order to compute an abnormality risk for each examination record. The TeleOphta
      system was trained and tested on a large dataset of 25,702 examination records
      from the OPHDIAT screening network in Paris. It was able to automatically detect
      68% of the non referable examination records while achieving the same sensitivity
      as a second ophthalmologist. This suggests that it could safely reduce the burden
      on ophthalmologists by 56%. 

PMID- 24111393
TI  - Integrating research, clinical practice and translation: the Singapore
      experience.
AB  - We introduce the experiences of the Singapore ocular imaging team, iMED, in
      integrating image processing and computer-aided diagnosis research with clinical
      practice and knowledge, towards the development of ocular image processing
      technologies for clinical usage with potential impact. In this paper, we outline
      key areas of research with their corresponding image modalities, as well as
      providing a systematic introduction of the datasets used for validation. 

PMID- 24111394
TI  - Towards a multi-site international public dataset for the validation of retinal
      image analysis software.
AB  - This paper discusses concisely the main issues and challenges posed by the
      validation of retinal image analysis algorithms. It is designed to set the
      discussion for the IEEE EBMC 2013 invited session "From laboratory to clinic: the
      validation of retinal image processing tools ". The session carries forward an
      international initiative started at EMBC 2011, Boston, which resulted in the
      first large-consensus paper (14 international sites) on the validation of retinal
      image processing software, appearing in IOVS. This paper is meant as a focus for
      the session discussion, but the ubiquity and importance of validation makes its
      contents, arguably, of interest for the wider medical image processing community.

PMID- 24111395
TI  - Accuracy improvement in Cranio-Maxillofacial soft tissue simulation using a
      muscle embedded meshing approach.
AB  - In the presented paper, we propose to improve the state-of-the-art approach for
      Cranio-Maxillofacial (CMF) soft tissue simulation by considering a new image
      based meshing approach that accurately models the interface between different
      tissue types. The proposed approach has been initially evaluated on soft tissue
      deformations of four patients undergoing CMF surgery using post-operative CT
      scans. The results indicate improved prediction and robustness of the surgical
      planning outcome when compared to the state-of-the-art method while decreasing
      the simulation time. 

PMID- 24111396
TI  - Phase velocity and attenuation predictions of waves in cancellous bone using an
      iterative effective medium approximation.
AB  - The quantitative determination of wave dispersion and attenuation in bone is an
      open research area as the factors responsible for ultrasound absorption and
      scattering in composite biological tissues have not been completely explained. In
      this study, we use the iterative effective medium approximation (IEMA) proposed
      in [1] so as to calculate phase velocity and attenuation in media with properties
      similar to those of cancellous bones. Calculations are performed for a frequency
      range of 0.4-0.8 MHz and for different inclusions' volume concentrations and
      sizes. Our numerical results are compared with previous experimental findings so
      as to assess the effectiveness of IEMA. It was made clear that attenuation and
      phase velocity estimations could provide supplementary information for cancellous
      bone characterization.

PMID- 24111397
TI  - A rectangular tetrahedral adaptive mesh based corotated finite element model for
      interactive soft tissue simulation.
AB  - In this paper, we propose a rectangular tetrahedral adaptive mesh based corotated
      finite element model for interactive soft tissue simulation. Our approach
      consists of several computation reduction techniques. They are as follows: 1) an
      efficient calculation approach for computing internal forces of nodes of elastic
      objects to take advantage of the rectangularity of the tetrahedral adaptive mesh;
      2) fast shape matching approach by using a new scaling of polar decomposition; 3)
      an approach for the reduction of the number of times of shape matching by using
      the hierarchical structure. We implemented the approach into our surgery
      simulator and compared the accuracy of the deformation and the computation time
      among 1) proposed approach, 2) L-FE), and 3) NL-FEM. Finally, we show the
      effectiveness of our proposed approach. 

PMID- 24111398
TI  - Modelling the generation of the cochlear microphonic.
AB  - The cochlear microphonic (CM) is one of the electrical signals generated by the
      human ear in response to sound stimulus. Difficulty in recording this signal and
      inadequate understanding of its origin have restricted its use for human auditory
      research. Modelling can help to improve our understanding of this signal. In this
      paper, an electromechanical model for the generation of the cochlear microphonic
      is proposed. The results of the model can also explain discrepancies between the
      basilar membrane and CM tuning curves. 

PMID- 24111399
TI  - Estimating muscle activation patterns using a surrogate model of facial
      biomechanics.
AB  - Analyzing the muscle activities that drive the expressive facial gestures can be
      a useful tool in assessing one's emotional state of mind. Since the skin motion
      is much easier to measure in comparison to the actual electrical excitation
      signal of facial muscles, a biomechanical model of the human face driven by these
      muscles can be a useful tool in relating the geometric information to the muscle
      activity. However, long computational time often hinders its practicality. The
      objective of this study was to replace the precise but computationally demanding
      biomechanical model by a much faster multivariate meta-model (surrogate model),
      such that a significant speedup (real-time interactive speed) can be achieved and
      data from the biomechanical model can be practically exploited. Using the
      proposed surrogate, muscle activation patterns of six key facial expressions were
      estimated in the iterative fit from the structured-light scanned geometric
      information. 

PMID- 24111400
TI  - Cardiac muscle strip model parameters and muscle elastance.
AB  - A recent functional model of the left ventricle as a pressure generator that is
      time and volume dependent was adapted to describe the mechanical aspects of heart
      muscle contraction. Muscle's complex dynamics develop from a single equation
      based on the formation and relaxation of crossbridge bonds. Muscle is modeled as
      a force generator that is time and length dependent. This equation permits the
      calculation of muscle elastance via Em = ?fm/?lm from muscle force and length,
      both as functions of time. This muscle model is defined independently from load
      properties, and elastance is dynamic and reflects changing numbers of crossbridge
      bonds. The model parameters were extracted from measured force and length data
      from cat papillary muscle experiments in the literature. The purpose of this
      paper is to present in some detail how to describe a particular muscle strip from
      measured data. The resulting model is tested under a wide range of mechanical
      conditions, such as isometric and isotonic contractions for normal and varied
      inotropic state, and muscle velocity is computed for different loads. Computed
      results compare favorably with similar measurements from the literature. The
      resulting lumped muscle model is a compact, yet comprehensive functional
      description of muscle dynamics.

PMID- 24111401
TI  - A new technique of bone thickness measurement for pedicle screw insertion safety
      purpose.
AB  - Pedicle Screw (PS) was originally accomplished for Spinal fixation but it has
      several limitations. If the pedicle screw passes though the cortex bone in
      surgery, it has a risk to damage the spinal cord and vertebral artery, which can
      be caused to a serious problem such as paralysis. Therefore, it should be avoided
      by all possible means. In current situation, it depends on a palpation of doctor
      to judge the boundary between the cortex and cancellous bone. Although many
      instrumentation has been described in several clinical studies, there are still
      lack of data in the literature concerning the measurement of bone thickness in
      real time mode. Most of the measurements of the bone thicknesses were based on CT
      Scan machine which is off-line technique. Therefore, the purpose of this
      prospective study was to develop a real time measurement of bone thickness for
      safety purpose of pedicle screw insertion. A total of 12 data was collected in
      each experiment. Ultrasound echo signal for each specimen was measured and used
      to measured bone thickness. Then, the results were compared with manual
      measurement of bone thickness which is by using a ruler. The percentage different
      of bone thickness was small for both methods which were 8.86% for first method
      and 15.1% for second method. This measurement values showed that the accuracy of
      bone thickness more than 84% for both method. As a conclusion, both methods were
      suitable to use as a bone thickness measurement technique for pedicle screw
      insertion application.

PMID- 24111402
TI  - Study on improvement of signal detectability considering noise characteristics in
      medical X-ray images.
AB  - The purpose of this study is to develop method for improvement of low-contrast
      signal detectability of general X-ray images used for observing overviews,
      included noise reduction technique and signal amplification technique, that are
      difficult to detect in the observing overview. The proposal method consists
      signal amplification part and noise reduction part. The noise reduction part
      first identifies and mathematizes the characteristics of the noise attributed to
      the X-ray imaging system before the subject is imaged. The noise information
      derived from mathematization is used to remove the noise representing the system
      noise from the subject image. After noise reduction, all the signals on the
      subject image with sufficiently reduced noise are amplified by multiplication
      with an arbitrary coefficient. The feasibility of the proposed method was
      indicated by three evaluations that were performed vision assessment using the
      image including the virtual low-contrast signals by four radiological
      technologists. That of the proposed method was confirmed from results of the
      evaluations. That of the proposed method was confirmed from results of the
      evaluations. 

PMID- 24111403
TI  - Multilingual medical dialog system developed as smartphone/tablet application.
AB  - Along with the concomitant rise in foreign residents in Japan has come the need
      to improve understanding at several social levels. The need for clear
      communication is most immediate in the area of the emergency or health care
      fields. Several types of apps exist that can be used to assist with communication
      between Japanese medical staff and foreign patients. However, there are problems
      with ease of use. This study asked 34 subjects to evaluate three types of touch
      designs with the "ExLanguage Nurse" to improve the usability of such multilingual
      apps. Results indicate that touch designs on the apps are related to ease of
      usability. 

PMID- 24111404
TI  - Usage of stereoscopic visualization in the learning contents of rotational
      motion.
AB  - Rotational motion plays an essential role in physics even at an introductory
      level. In addition, the stereoscopic display of three-dimensional graphics
      includes is advantageous for the presentation of rotational motions, particularly
      for depth recognition. However, the immersive visualization of rotational motion
      has been known to lead to dizziness and even nausea for some viewers. Therefore,
      the purpose of this study is to examine the onset of nausea and visual fatigue
      when learning rotational motion through the use of a stereoscopic display. The
      findings show that an instruction method with intermittent exposure of the
      stereoscopic display and a simplification of its visual components reduced the
      onset of nausea and visual fatigue for the viewers, which maintained the overall
      effect of instantaneous spatial recognition. 

PMID- 24111405
TI  - Accommodation training in foreign workers.
AB  - By relaxing the contracted focus-adjustment muscles around the eyeball, known as
      the ciliary and extraocular muscles, the degree of pseudomyopia can be reduced.
      This understanding has led to accommodation training in which a visual target is
      presented in stereoscopic video clips. However, it has been pointed out that
      motion sickness can be induced by viewing stereoscopic video clips. In
      Measurement 1 of the present study, we verified whether the new 3D technology
      reduced the severity of motion sickness in accordance with stabilometry. We then
      evaluated the short-term effects of accommodation training using new stereoscopic
      video clips on foreign workers (11 females) suffering from eye fatigue in
      Measurement 2. The foreign workers were trained for three days. As a result,
      visual acuity was statistically improved by continuous accommodation training,
      which will help promote ciliary muscle stretching. 

PMID- 24111406
TI  - Comparison of form in potential functions while maintaining upright posture
      during exposure to stereoscopic video clips.
AB  - Visually induced motion sickness (VIMS) is caused by sensory conflict, the
      disagreement between vergence and visual accommodation while observing
      stereoscopic images. VIMS can be measured by psychological and physiological
      methods. We propose a mathematical methodology to measure the effect of three
      dimensional (3D) images on the equilibrium function. In this study, body sway in
      the resting state is compared with that during exposure to 3D video clips on a
      liquid crystal display (LCD) and on a head mounted display (HMD). In addition,
      the Simulator Sickness Questionnaire (SSQ) was completed immediately afterward.
      Based on the statistical analysis of the SSQ subscores and each index for
      stabilograms, we succeeded in determining the quantity of the VIMS during
      exposure to the stereoscopic images. Moreover, we discuss the metamorphism in the
      potential functions to control the standing posture during the exposure to
      stereoscopic video clips. 

PMID- 24111407
TI  - A mobile system for assessment of physiological response to posture transitions.
AB  - Posture changes initiate a dynamic physiological response that can be used as an
      indicator of the overall health status. We introduce an inconspicuous mobile
      wellness monitoring system (imWell) that continuously assesses the dynamic
      physiological response to posture transitions during activities of daily living.
      imWell utilizes a Zephyr BioHarness 3 physiological monitor that continually
      reports heart activity and physical activity via Bluetooth to a personal device
      (e.g. smartphone). The personal device processes the reported activity data in
      real-time to recognize posture transitions from the accelerometer data and to
      characterize dynamic heart response to posture changes. It annotates, logs, and
      uploads the heart activity data to our mHealth server. In this paper we present
      algorithms for detection of posture transitions and heart activity
      characterization during a sit-to-stand transition. The proposed system was tested
      on seven healthy subjects performing a predefined protocol. The total average and
      standard deviation for sit-to-stand transition time is 2.7 +/- 0.69 s, resulting
      in the change of heart rate of 27.36 +/- 9.30 bpm (from 63.3 +/- 9.02 bpm to
      90.66 +/- 10.09 bpm).

PMID- 24111408
TI  - Development of SmartStep: an insole-based physical activity monitor.
AB  - In our previous research we developed a SmartShoe--a shoe based physical activity
      monitor that can reliably differentiate between major postures and activities,
      accurately estimate energy expenditure of individuals, measure temporal gait
      parameters, and estimate body weights. In this paper we present the development
      of the next stage of the SmartShoe evolution--SmartStep, a physical activity
      monitor that is fully integrated into an insole, maximizing convenience and
      social acceptance of the monitor. Encapsulating the sensors, Bluetooth Low Energy
      wireless interface and the energy source within an assembly repeatedly loaded
      with high forces created during ambulation presented new design challenges. In
      this preliminary study we tested the ability of the SmartStep to measure the
      pressure differences between static weight-bearing and non-weight-bearing
      activities (such as no load vs. sitting vs. standing) as well as capture pressure
      variations during walking. We also measured long-term stability of the sensors
      and insole assembly under cyclic loading in a mechanical testing system.

PMID- 24111409
TI  - Measurement of knee flexion/extension angle using wearable UWB radios.
AB  - This paper proposes a wearable system using UWB transceivers to measure the knee
      flexion/extension angle parameter, who is known to be of clinical importance.
      First, a pair of very small and light antennas is placed on the adjacent segments
      of knee joint. Then, the range data between these two antennas is acquired using
      Time of Arrival (TOA) estimator. We further use the measured distance to compute
      the flexion/extension angle using the law of cosines. The performance of the
      method was compared with a flexible goniometer by simultaneously measuring knee
      flexion-extension angle. The experimental results show that the system has
      reasonable performance and has sufficient accuracy for clinical applications. 

PMID- 24111410
TI  - Quantitative analysis of the fall-risk assessment test with wearable inertia
      sensors.
AB  - We performed a quantitative analysis of the fall-risk assessment test using a
      wearable inertia sensor focusing on two tests: the time up and go (TUG) test and
      the four square step test (FSST). These tests consist of various daily
      activities, such as sitting, standing, walking, stepping, and turning. The TUG
      test was performed by subjects at low and high fall risk, while FSST was
      performed by healthy elderly and hemiplegic patients with high fall risk. In
      general, the total performance time of activities was evaluated. Clinically, it
      is important to evaluate each activity for further training and management. The
      wearable sensor consisted of an accelerometer and angular velocity sensor. The
      angular velocity and angle of pitch direction were used for TUG evaluation, and
      those in the pitch and yaw directions at the thigh were used for FSST. Using the
      threshold of the angular velocity signal, we classified the phase corresponding
      to each activity. We then observed the characteristics of each activity and
      recommended suitable training and management. The wearable sensor can be used for
      more detailed evaluation in fall risk management. The wearable sensor can be used
      more detailed evaluation for fall-risk management test. 

PMID- 24111411
TI  - 3-D kinematics and neuromuscular signals' integration for post ACL reconstruction
      recovery assessment.
AB  - An intelligent recovery classification and monitoring system (IRCMS) for post
      Anterior Cruciate Ligament (ACL) reconstruction has been developed in this study.
      This system provides an objective assessment and monitoring of the rehabilitation
      progress by integrating 3-D kinematics and neuromuscular signals recorded through
      wearable motion and electromyography sensors, respectively. The data from a group
      of healthy and ACL reconstructed subjects were collected for normal/brisk walking
      (4-6km/h) and single leg balance (eyes open and eyes closed) testing activities.
      Fuzzy clustering and fuzzy nearest neighbor methods have been used to classify
      the collected data into different groups for each activity. The classification
      accuracy of the system is found to be 94.49% for 4 km/h walking speed, 95.41% for
      5 km/h walking speed, 96.00% for 6 km/h walking speed, 94.44% for single leg
      balance testing with eyes open and 95.83% for single leg balance testing with
      eyes closed. The recovery status of a subject is evaluated based on different
      activities assessed and the overall assessment is done using Choquet integral
      fusion technique. Further, biofeedback mechanism has been developed using a
      visual monitoring system which provides the variations in strength/activation of
      knee flexors/extensors and 3-D joint kinematics. This integrated system can be
      used as an assistive tool by sports trainers, coaches and clinicians for
      monitoring overall progress of athletes' rehabilitation and classifying their
      recovery stage for multiple activities. 

PMID- 24111412
TI  - An EKF-based approach for estimating leg stiffness during walking.
AB  - The spring-like behavior is an inherent condition for human walking and running.
      Since leg stiffness k(leg) is a parameter that cannot be directly measured, many
      techniques has been proposed in order to estimate it, most of them using force
      data. This paper intends to address this problem using an Extended Kalman Filter
      (EKF) based on the Spring-Loaded Inverted Pendulum (SLIP) model. The formulation
      of the filter only uses as measurement information the Center of Mass (CoM)
      position and velocity, no a priori information about the stiffness value is
      known. From simulation results, it is shown that the EKF-based approach can
      generate a reliable stiffness estimation for walking.

PMID- 24111413
TI  - The effect of vary varus malalignment on knee adduction moment during walking of
      human normal gait.
AB  - This research aims to study the effect of varus malalignment to knee adduction
      moment (KAM) during walking using 3D gait simulation. KAM is the product of
      frontal ground reaction force and frontal lever arm; it is a major cause of pain
      at the lateral knee that is the general symptom of osteoarthritis (OA). For
      treatment, lateral fixed wedge insole and variable-stiffness shoes were used to
      treat OA patient for many years. The device helps reduce KAM while walking by
      shifting the center of pressure (CoP) from medial side to lateral side.
      Therefore, shifting CoP to lateral side for reducing frontal lever arm was
      incorporated into the design of the treatment devices for OA patient. In this
      paper, program simulation "Adams life module" was used to create 3D human model
      and simulate 3D gait to observe changes of KAM while vary the adduction angle
      between thigh and tibia. The simulation model was created based on normal gait
      profile data during the movement of the model. The result obtained from the
      simulation showed that the varus malalignment plays important roles on KAM.
      Increasing of the adduction angle leads to the higher value of peak KAM during
      walking. 

PMID- 24111414
TI  - Multijoint upper limb torque estimation from sEMG measurements.
AB  - Estimation of joint torques through musculoskeletal models and measurements of
      muscle activations can be used for real-time control of robotic devices for
      rehabilitation. Many works developed models for analytic one joint motion, but
      less are found that develop models for functional multijoint movements. In this
      work we develop a methodology for tuning and optimizing Hill-based EMG-driven
      models oriented to the force control of robotic exoskeletons for the upper limb,
      selecting the more suitable parameters to be optimized. The model is tuned from
      experimental data obtained from healthy people. The torques estimated by that
      model will serve as reference for force-based control of an exoskeleton for
      rehabilitation. 

PMID- 24111415
TI  - Sport helmet design and virtual impact test by image-based finite element
      modeling.
AB  - Head injury has been a major concern in various sports, especially in contact
      sports such as football and ice hockey. Helmet has been adopted as a protective
      device in such sports, aiming at preventing or at least alleviating head
      injuries. However, there exist two challenges in current helmet design and test.
      One is that the helmet does not fit the subject's head well; the other is that
      current helmet testing methods are not able to provide accurate information about
      intracranial pressure and stress/strain level in brain tissues during impact. To
      meet the challenges, an image-based finite element modeling procedure was
      proposed to design subject-specific helmet and to conduct virtual impact test. In
      the procedure, a set of medical images such as computed tomography (CT) and
      magnetic resonance image (MRI) of the subject's head was used to construct
      geometric shape of the helmet and to develop a helmet-head finite element model
      that can be used in the virtual impact test. 

PMID- 24111416
TI  - Local dynamic stability of lower extremity joints in lower limb amputees during
      slope walking.
AB  - Lower limb amputees have a higher fall risk during slope walking compared with
      non-amputees. However, studies on amputees' slope walking were not well
      addressed. The aim of this study was to identify the difference of slope walking
      between amputees and non-amputees. Lyapunov exponents lambdaS was used to
      estimate the local dynamic stability of 7 transtibial amputees' and 7 controls'
      lower extremity joint kinematics during uphill and downhill walking. Compared
      with the controls, amputees exhibited significantly lower lambdaS in hip (P=0.04)
      and ankle (P=0.01) joints of the sound limb, and hip joints (P=0.01) of the
      prosthetic limb during uphill walking, while they exhibited significantly lower
      lambdaS in knee (P=0.02) and ankle (P=0.03) joints of the sound limb, and hip
      joints (P=0.03) of the prosthetic limb during downhill walking. Compared with
      amputees level walking, they exhibited significantly lower lambdaS in ankle
      joints of the sound limb during both uphill (P=0.01) and downhill walking
      (P=0.01). We hypothesized that the better local dynamic stability of amputees was
      caused by compensation strategy during slope walking. 

PMID- 24111417
TI  - Motion recognition from contact force measurement.
AB  - Optical motion capture systems, which are used in broad fields of research, are
      costly; they need large installation space and calibrations. We find difficulty
      in applying it in typical homes and care centers. Therefore we propose to use low
      cost contact force measurement systems to develop rehabilitation and healthcare
      monitoring tools. Here, we propose a novel algorithm for motion recognition using
      the feature vector from force data solely obtained during a daily exercise
      program. We recognized 7 types of movement (Radio Exercises) of two candidates
      (mean age 22, male). The results show that the recognition rate of each motion
      has high score (mean: 86.9%). The results also confirm that there is a clustering
      of each movement in personal exercises data, and a similarity of the clustering
      even for different candidates thus that motion recognition is possible using
      contact force data. 

PMID- 24111418
TI  - Realistic biomechanical model of a cancerous breast for the registration of prone
      to supine deformations.
AB  - We develop a large deformations, Finite Elements biomechanical model of a
      stellate breast tumour, subject to prone to supine (MRI to US) breast
      deformations. Based on clinical findings, we introduce a volume of increased
      mammographic density/stiffness around a spiculated tumour, as well as a range of
      reported mechanical properties, both linear elastic and hyperelastic. This novel
      model demonstrates that these have a non-negligible effect on stresses and
      displacements, which, in turn, have implications, for example, in breast
      registration. We also show that the choice of material properties plays a
      dramatic effect on the mechanical variables. 

PMID- 24111419
TI  - M-health medical video communication systems: an overview of design approaches
      and recent advances.
AB  - The emergence of the new, High Efficiency Video Coding (HEVC) standard, combined
      with wide deployment of 4G wireless networks, will provide significant support
      toward the adoption of mobile-health (m-health) medical video communication
      systems in standard clinical practice. For the first time since the emergence of
      m-health systems and services, medical video communication systems can be
      deployed that can rival the standards of in-hospital examinations. In this paper,
      we provide a thorough overview of today's advancements in the field, discuss
      existing approaches, and highlight the future trends and objectives. 

PMID- 24111420
TI  - Toward energy-efficient and distributed mobile health monitoring using parallel
      offloading.
AB  - Although mobile health monitoring where mobile sensors continuously gather,
      process, and update sensor readings (e.g. vital signals) from patient's sensors
      is emerging, little effort has been investigated in an energy-efficient
      management of sensor information gathering and processing. Mobile health
      monitoring with the focus of energy consumption may instead be holistically
      analyzed and systematically designed as a global solution to optimization
      subproblems. We propose a distributed and energy-saving mobile health platform,
      called mHealthMon where mobile users publish/access sensor data via a cloud
      computing-based distributed P2P overlay network. The key objective is to satisfy
      the mobile health monitoring application's quality of service requirements by
      modeling each subsystem: mobile clients with medical sensors, wireless network
      medium, and distributed cloud services. By simulations based on experimental
      data, we present the proposed system can achieve up to 10.1 times more energy
      efficient and 20.2 times faster compared to a standalone mobile health monitoring
      application, in various mobile health monitoring scenarios applying a realistic
      mobility model. 

PMID- 24111421
TI  - A portable real-time ECG recognition system based on smartphone.
AB  - This paper proposed an smartphone-based real-time ECG monitoring and recognition
      system. The ECG signal was acquired by a MSP430FG4618 low-power microprocessor
      and was converted via a Bluetooth module for wireless transmission to a
      smartphone. A noise-tolerant ECG heartbeat recognition algorithm based on
      discrete wavelet transform and higher-order statistics was employed to identify
      different types of heartbeats. This system achieved a high accuracy of 98.34 % in
      identifying seven heartbeat types, which was demonstrated to outperform other
      studies in the literature. The heartbeat types were recognized in real-time; only
      78 ms was required to identify a heartbeat. The portability, real-time
      processing, and high recognition rate of the system demonstrate the efficiency
      and effectiveness of the device as a practical computer-aided diagnosis (CAD)
      system. 

PMID- 24111422
TI  - Development of lifelog sharing system for rheumatoid arthritis patients using
      smartphone.
AB  - In this paper, we report the development of a lifelog sharing system for
      rheumatoid arthritis patients. Our system can objectively assess patients'
      condition from day to day via their smartphone use. We conducted a field
      experiment to investigate the feasibility of lifelog collection and sharing. The
      rate of patient assessment is very high. The system collects daily change in
      patients' activity as influenced by the disease. 

PMID- 24111423
TI  - Design and evaluation of a multimodal mHealth based medication management system
      for patient self administration.
AB  - The intake of prescribed medication presents a challenge, in particular for
      elderly people and in cases where a variety of medications have to be taken in
      accordance to a complex schedule. To support patients with this task, an mHealth
      concept was developed and evaluated in the course of a clinical trial. The system
      used a multimodal user interface concept, i.e. both RFID tags and barcodes to
      identify and document the intake of medications. Results of the clinical study
      with 20 patients indicate that the multimodal mHealth concept utilizing barcode
      and RFID tags enabled easy-to-use medication management. Although further
      clinical evaluation is needed to assess whether such a tool can also enhance
      adherence, the system shows the potential for targeting the problem of medication
      management with mHealth methods. 

PMID- 24111424
TI  - Comparing stress markers across various cohorts in a mobile setting.
AB  - There exist multiple markers for measuring psychological stress, with varying
      specificities and sensitivities. However, in a real-life setting, there is
      limited data on how robust these methods may be especially in a relatively mobile
      context where the signal fidelity maybe limited. Thus any large scale data to
      inform how these methods perform, using commonly available sensors, based on both
      context and cohort characterization, can greatly add to our knowledge of their
      respective utility in real-life settings. This paper presents a study of 253
      subjects which provides crucial data for analysing various stress markers in a
      mobile setting. We also provide early analysis results. 

PMID- 24111425
TI  - A new seismocardiography segmentation algorithm for diastolic timed vibrations.
AB  - An algorithm based on the combination of electrocardiography (ECG) and
      seismocardiogranphy (SCG) is used to detect the start and the end of diastole in
      diastolic timed vibrations (DTV). The proposed algorithm uses the ECG-R wave as
      the reference point and detects the aortic valve closure (AC) and mitral valve
      closure (MC) points of the SCG signal. This algorithm enables DTV to operate very
      efficiently in comparison with previous ECG based algorithm. Prediction rate of
      95 and 88 percent was achieved for detection of SCG-MC and SCG-AC respectively. 

PMID- 24111426
TI  - Physiological insights from gravity-free ballistocardiography.
AB  - Terrestrial ballistocardiographic (BCG) measurements are typically performed in
      only one or two axes because of the coupling between the subject and the ground.
      An appropriate physiological interpretation of these BCG signals therefore
      assumes that the information in the unmeasured axis is either understood, or able
      to be ignored. BCG signals from measurements in microgravity can be made in all
      three axes and permit examination of these assumptions. Such microgravity
      measurements show that lung volume significantly affects the BCG signals,
      predominately in the head-to-foot direction. Further, the maximum accelerations
      recorded following systole are poorly captured by coronal plane measurements as
      the greatest displacements occur in the sagittal plane. These results suggest a
      need to carefully consider the influence of the motion in the unmeasured plane
      when interpreting terrestrial BCG signals. 

PMID- 24111427
TI  - A preliminary study investigating the quantification of beat-to-beat in
      seismocardiogram signals.
AB  - Ballistocardiography and seismocardiography are both non-invasive mechanical
      measurements of the vibrations of the body in response to the heartbeat. The
      ballistocardiogram (BCG) signal represents the movements of the whole body in
      response to cardiac ejection of blood into the vasculature; the seismocardiogram
      (SCG) corresponds to local vibrations of the chest wall associated with sub
      audible tissue and blood movement and audio frequency heart-valve closure
      dynamics. This paper focuses on methods for quantifying "signal consistency"--a
      quantitative measure of how morphologically similar each heartbeat in a patient's
      recording is compared to the ensemble average taken over the recording. Before
      comparing each beat to the average, known physiological sources of inconsistency-
      such as respiratory amplitude and timing variability--are removed, then the
      remaining inconsistency is quantified. Previously described methods for BCG
      signals are expanded to fit the high-frequency (> 20 Hz) components of the SCG.
      The use of this method in future work could help enable proactive management of
      heart disease in extra-clinical settings.

PMID- 24111428
TI  - Preliminary results from standing ballistocardiography measurements in
      microgravity.
AB  - We report on the feasibility of standing ballistocardiogram (BCG) measurements
      recorded in a microgravity environment. A clinically-tested BCG monitoring scale
      was adapted for parabolic flight for the microgravity measurements. Upon
      completion of this flight campaign, the BCG scale was shown to make measurements
      in micro-g and one-g environments--which is a first demonstration for a standing
      BCG system. This screening experiment demonstrated proof-of-concept attributes of
      the hardware design necessary for future characterization studies with multiple
      subjects. This scale-based BCG system is proposed as a practical device for
      hemodynamic monitoring for astronauts in Earth, Lunar, Martian, orbital, and
      interplanetary environments.

PMID- 24111429
TI  - Timing and source of the maximum of the transthoracic impedance cardiogram
      (dZ/dt) in relation to the H-I-J complex of the longitudinal ballistocardiogram
      under gravity and microgravity conditions.
AB  - The transthoracic impedance cardiogram (ICG) and the acceleration
      ballistocardiogram (BCG) measured close to the center of mass of the human body
      are generated by changes of blood distribution. The transthoracic ICG is an
      integrated signal covering the whole thorax and spatial resolution is poor.
      Comparison between both signals can be used to elucidate the source of the ICG
      signal. We recorded the ECG, ICG, and BCG simultaneously in healthy subjects
      under resting and microgravity conditions during parabolic flights. The time
      interval between the R-peak of the ECG and the maximum of the ICG (R-dZ/dtmax)
      and the time interval between the R-peak of the ECG and the I-peak in the BCG (R
      I) differed significantly (p<0.0001). The I-peak in the BCG always occurred
      earlier during systole than dZ/dtmax. The delay of dZ/dtmax ranged between 23 and
      28 ms at rest and was lowest under microgravity conditions (12 +/- 4 ms, p<0.02).
      Our results suggest that both signals have different sources. Combination of
      modern imaging techniques with classical non invasive approaches to detect
      changes of blood distribution may provide new insights into the complex
      interaction between blood flow and mechanocardiographic signals like the BCG.

PMID- 24111430
TI  - The Sweet-Home project: audio processing and decision making in smart home to
      improve well-being and reliance.
AB  - The Sweet-Home project aims at providing audio-based interaction technology that
      lets the user have full control over their home environment, at detecting
      distress situations and at easing the social inclusion of the elderly and frail
      population. This paper presents an overview of the project focusing on the
      implemented techniques for speech and sound recognition as context-aware decision
      making with uncertainty. A user experiment in a smart home demonstrates the
      interest of this audio-based technology. 

PMID- 24111431
TI  - Development of an image processing support system based on fluorescent dye to
      prevent elderly people with dementia from wandering.
AB  - The wandering of elderly people with dementia is a significant behavioral problem
      and is a heavy burden on caregivers in residential and nursing homes. Thus,
      warning systems have been developed to prevent elderly people with dementia from
      leaving the premises. Some of these systems use radio waves. However, systems
      based on radio waves present several practical problems. For instance, the
      transmitter must be carried and may become lost; in addition, the battery of the
      transmitter must be changed. To solve these problems, we developed a support
      system that prevents elderly people with dementia from wandering. The system
      employs image processing technology based on fluorescent dye. The composition of
      the support system can be described as follows: fluorescent dye is painted in a
      simple shape on the clothes of an elderly person. The fluorescent color becomes
      visible by irradiation with a long wavelength of ultraviolet light. In the
      present paper, the relationship between the color of the dye and the cloth was
      investigated. A 3D video camera was used to acquire a 3D image and detect the
      simple shape. As a preliminary experiment, 3 colors (red, green and blue) of
      fluorescent dye were applied to cloths of 9 different colors. All fluorescent
      colors were detected on 6 of the cloths, but red and blue dye could not be
      detected on the other 3 cloths. In contrast, green dye was detectable on all 9 of
      the cloths. Additionally, we determined whether green dye could be detected in an
      actual environment. A rectangular shaped patch of green fluorescent dye was
      painted on the shoulder area of a subject, from the scapula to the clavicle. As a
      result, the green dye was detected on all 9 different colored cloths. 

PMID- 24111432
TI  - Feasibility of a wireless health monitoring system for prevention and health
      assessment of elderly people.
AB  - The work presented in this paper comprises the methodology and results of a pilot
      study on the feasibility of a wireless health monitoring system designed under
      main EU challenges for the promotion of healthy and active ageing. The system is
      focused on health assessment, prevention and lifestyle promotion of elderly
      people. Over a hundred participants including elderly users and caregivers tested
      the system in four pilot sites across Europe. Tests covered several scenarios in
      senior centers and real home environments, including performance and usability
      assessment. Results indicated strong satisfactoriness on usability, usefulness
      and user friendliness, and the acceptable level of reliability obtained supports
      future investigation on the same direction for further improvement and transfer
      of conclusions to the real world in the healthcare delivery. 

PMID- 24111433
TI  - Remotely controlled cycling exercise system for home-based telerehabilitation.
AB  - Limited research has been conducted in utilizing telemedicine to promote upper
      and lower limb rehabilitation using remotely controlled home-based ergometers.
      The goal of this study was to develop and assess a telerehabilitation system
      supporting internet-controlled home-based cycling exercise. We designed an
      interface to control cycling speed of an ergometer from a remote server via
      Internet. The evaluation of the interface included consecutive transmission of 7
      different cycling speed levels, each level of 2-minute duration. Overall, the
      mean difference between remotely setup and actual cycling speed was 0.002 +/-
      0.03 miles/hour. Our evaluation demonstrated high fidelity of the proposed system
      and reliability of controlling individualized exercise prescription for home
      based cycling equipment via Internet.

PMID- 24111434
TI  - Predictors of successful acceptance of home telemanagement in veterans with
      Multiple Sclerosis.
AB  - Modern telehealth technologies may be instrumental in overcoming the barriers of
      optimal care delivery for patients with MS. However, the significant potential of
      telemedicine approaches in improving MS care has not yet been fully explored. The
      Multiple Sclerosis Centers of Excellence of the Department of Veterans Affairs
      (VA) has been actively promoting the use of telemedicine in helping veterans with
      MS. Particular attention was given to the development of cost-effective care
      coordination solutions which can be easily delivered directly to each veteran
      home via internet and accessed via a regular computer or a mobile device. In this
      article, the design of the MS HAT system is introduced and results of the initial
      feasibility evaluation are presented. The feasibility of the MS HAT system was
      assessed by (1) analyzing attitudinal surveys of veterans with MS who used the MS
      HAT system at home for over a month; (2) identifying factors affecting acceptance
      of the MS HAT system; (3) reviewing adherence of MS HAT users to self-testing
      regimen; (4) analyzing veteran feedback on MS HAT functionality using semi
      structured qualitative interviews. 

PMID- 24111435
TI  - Adaptive and automated ambiance surveillance and event detection for Ambient
      Assisted Living.
AB  - In this paper, we discuss an event detection system using a wireless sensor
      network in the Ambient Assisted Living context. The sensors measure the
      environment in which the patients live, not vital parameters of the patient him-
      or herself, which is important in order to respect the privacy and informational
      self-determination of the patient. The major difficulties of the given setup with
      sensors in the environment are that the measurements are taken in an irregular
      fashion (as opposed to regular sampling) and that some of the sensors may be
      unreliable. To tackle these problems, we propose an event-detection framework
      that is based on the theory of conditional random fields [1]. We conduct
      experiments on real-life sensor data collected from a set of eight households.
      The experiments show that the conditional random field is well suited for
      ambiance surveillance. 

PMID- 24111436
TI  - Coordinate rotation based low complexity architecture for 3D Single Channel
      Independent Component Analysis.
AB  - In this paper, we have proposed a low complexity architecture of the Single
      Channel Independent Component Analysis Algorithm (SCICA) targeted for remote
      cardiac health monitoring by introducing the concept of coordinate rotation. The
      ECG is widely used for the diagnosis of cardiovascular diseases, and in remote
      healthcare applications, it is necessary to obtain clean ECG data by separating
      noise from the obtained signal. Independent Component Analysis is popularly used
      to solve the signal separation problem, however it requires as many signal
      sensors as the number of independent signals involved, and also requires the
      number of signals involved to be known a priori. This is not always possible in
      remote healthcare environments and thus, this motivates us to explore the use of
      the SCICA algorithm which requires only one input sensor for signal separation.
      SCICA is computationally intensive and thus there is a need for a low-complexity
      implementation of the algorithm for the development of healthcare devices. The
      proposed architecture is validated in terms of functionality and computational
      complexity and it has been observed that its performance compares favorably with
      the conventional algorithm. 

PMID- 24111437
TI  - Detection of myocardial scar from the VCG using a supervised learning approach.
AB  - This paper addresses the possibility of detecting presence of scar tissue in the
      myocardium through the investigation of vectorcardiogram (VCG) characteristics.
      Scarred myocardium is the result of myocardial infarction (MI) due to ischemia
      and creates a substrate for the manifestation of fatal arrhythmias. Our efforts
      are focused on the development of a classification scheme for the early screening
      of patients for the presence of scar. More specifically, a supervised learning
      model based on the extracted VCG features is proposed and validated through
      comprehensive testing analysis. The achieved accuracy of 82.36% (sensitivity
      84.31%, specificity 77.36%) indicates the potential of the proposed screening
      mechanism for detecting the presence/absence of scar tissue. 

PMID- 24111438
TI  - Noise-tolerant instantaneous heart rate and R-peak detection using short-term
      autocorrelation for wearable healthcare systems.
AB  - This paper describes a robust method of Instantaneous Heart Rate (IHR) and R-peak
      detection from noisy electrocardiogram (ECG) signals. Generally, the IHR is
      calculated from the R-wave interval. Then, the R-waves are extracted from the ECG
      using a threshold. However, in wearable bio-signal monitoring systems, noise
      increases the incidence of misdetection and false detection of R-peaks. To
      prevent incorrect detection, we introduce a short-term autocorrelation (STAC)
      technique and a small-window autocorrelation (SWAC) technique, which leverages
      the similarity of QRS complex waveforms. Simulation results show that the
      proposed method improves the noise tolerance of R-peak detection. 

PMID- 24111439
TI  - Detection of myocardial ischemia episode using morphological features.
AB  - In this study, we propose to use morphological features that are easy to identify
      to differentiate myocardial ischemic beats from normal beats. In general,
      myocardial ischemia causes alterations in electrocardiographic (ECG) signal such
      as deviation in the ST segment. When the ST segment level deviates from a certain
      voltage, the beat would be diagnosing as myocardial ischemia. To emphasize on ST
      variations, the QRS complex of the ECG signal was first subtracted and replaced
      with a straight line. Five-level discrete wavelet transform (DWT) followed to
      decompose the waveform into subband components and the A5 subband, which is most
      sensitive to the changes in the ST segment, was reconstructed for the calculation
      of 12 morphological features. The support vector machine (SVM) and the 10-fold
      cross-validation method were employed to evaluate the performance of the method.
      The results show high values of 95.20%, 93.29%, and, 93.63% in sensitivity,
      specificity, and accuracy, respectively, that were demonstrated to outperform the
      other methods in the literature. 

PMID- 24111440
TI  - Reconstruction of fetal vector electrocardiogram from maternal abdominal signals
      under fetus body rotations.
AB  - Fetal electrocardiogram (fECG) and its vector form (fVECG) could provide
      significant clinical information concerning physiological conditions of a fetus.
      So far various independent component analysis (ICA)-based methods for extracting
      fECG from maternal abdominal signals have been proposed. Because full extraction
      of component waves such as P, Q, R, S, and T, is difficult to be realized under
      noisy and nonstationary situations, the fVECG is further hard to be
      reconstructed, where different projections of the fetal heart vector are
      required. In order to reconstruct fVECG, we proposed a novel method for
      synthesizing different projections of the heart vector, making good use of the
      fetus movement. This method consists of ICA, estimation of rotation angles of
      fetus, and synthesis of projections of the heart vector. Through applications to
      the synthetic and actual data, our method is shown to precisely estimate rotation
      angle of the fetus and to successfully reconstruct the fVECG. 

PMID- 24111442
TI  - Enhanced imaging colonoscopy facilitates dense motion-based 3D reconstruction.
AB  - We propose a novel approach for estimating a dense 3D model of neoplasia in
      colonoscopy using enhanced imaging endoscopy modalities. Estimating a dense 3D
      model of neoplasia is important to make 3D measurements and to classify the
      superficial lesions in standard frameworks such as the Paris classification.
      However, it is challenging to obtain decent dense 3D models using computer vision
      techniques such as Structure-from-Motion due to the lack of texture in
      conventional (white light) colonoscopy. Therefore, we propose to use enhanced
      imaging endoscopy modalities such as Narrow Band Imaging and chromoendoscopy to
      facilitate the 3D reconstruction process. Thanks to the use of these enhanced
      endoscopy techniques, visualization is improved, resulting in more reliable
      feature tracks and 3D reconstruction results. We first build a sparse 3D model of
      neoplasia using Structure-from-Motion from enhanced endoscopy imagery. Then, the
      sparse reconstruction is densified using a Multi-View Stereo approach, and
      finally the dense 3D point cloud is transformed into a mesh by means of Poisson
      surface reconstruction. The obtained dense 3D models facilitate classification of
      neoplasia in the Paris classification, in which the 3D size and the shape of the
      neoplasia play a major role in the diagnosis. 

PMID- 24111441
TI  - Automated classification of spatiotemporal characteristics of gastric slow wave
      propagation.
AB  - Gastric contractions are underpinned by an electrical event called slow wave
      activity. High-resolution electrical mapping has recently been adapted to study
      gastric slow waves at a high spatiotemporal detail. As more slow wave data
      becomes available, it is becoming evident that the spatial organization of slow
      wave plays a key role in the initiation and maintenance of gastric dsyrhythmias
      in major gastric motility disorders. All of the existing slow wave signal
      processing techniques deal with the identification and partitioning of recorded
      wave events, but not the analysis of the slow wave spatial organization, which is
      currently performed visually. This manual analysis is time consuming and is prone
      to observer bias and error. We present an automated approach to classify spatial
      slow wave propagation patterns via the use of Pearson cross correlations. Slow
      wave propagations were grouped into classes based on their similarity to each
      other. The method was applied to high-resolution gastric slow wave recordings
      from four pigs. There were significant changes in the velocity of the gastric
      slow wave wavefront and the amplitude of the slow wave event when there was a
      change in direction to the slow wave wavefront during dsyrhythmias, which could
      be detected with the automated approach. 

PMID- 24111443
TI  - Impact of image preprocessing methods on polyp localization in colonoscopy
      frames.
AB  - In this paper we present our image preprocessing methods as a key part of our
      automatic polyp localization scheme. These methods are used to assess the impact
      of different endoluminal scene elements when characterizing polyps. More
      precisely we tackle the influence of specular highlights, blood vessels and black
      mask surrounding the scene. Experimental results prove that the appropriate
      handling of these elements leads to a great improvement in polyp localization
      results. 

PMID- 24111444
TI  - A new method for pulmonary nodule detection using decision trees.
AB  - A computer-aided detection (CAD) can help radiologists in diagnosing of lung
      diseases at an early level. In this study, a new CAD system for pulmonary nodule
      detection from CT imagery is presented by using morphological features and
      patient information properties. Decision trees are utilized for classification
      and overall detection performance is evaluated. Results are compared to similar
      techniques in the literature by using standard measures. Proposed CAD system with
      random forest classifier result in 90.5 % sensitivity and 87.6 % specificity of
      detection performance. 

PMID- 24111445
TI  - A multiscale product approach for an automatic classification of voice disorders
      from endoscopic high-speed videos.
AB  - Direct observation of vocal fold vibration is indispensable for a clinical
      diagnosis of voice disorders. Among current imaging techniques, high-speed
      videoendoscopy constitutes a state-of-the-art method capturing several thousand
      frames per second of the vocal folds during phonation. Recently, a method for
      extracting descriptive features from phonovibrograms, a two-dimensional image
      containing the spatio-temporal pattern of vocal fold dynamics, was presented. The
      derived features are closely related to a clinically established protocol for
      functional assessment of pathologic voices. The discriminative power of these
      features for different pathologic findings and configurations has not been
      assessed yet. In the current study, a collective of 220 subjects is considered
      for two- and multi-class problems of healthy and pathologic findings. The
      performance of the proposed feature set is compared to conventional feature
      reduction routines and was found to clearly outperform these. As such, the
      proposed procedure shows great potential for diagnostical issues of vocal fold
      disorders. 

PMID- 24111446
TI  - Markerless tracking for augmented reality for image-guided Endoscopic Retrograde
      Cholangiopancreatography.
AB  - This paper proposes a markerless tracking method with adaptive pose estimation
      for augmenting 3D organ models on top of the endoscopic image for Endoscopic
      Retrograde Cholangiopancreatography (ERCP). While many applications of augmented
      reality (AR) to surgeries need special markers to track the camera's position and
      orientation in the live video, our method employs the feature detection
      techniques to track the endoscopic camera. One of the most difficult problems
      when applying feature-based method to AR for ERCP is the lack of texture & highly
      specular reflection surface of duodenum in the endoscopic images, which does not
      provide a stable number of keypoints to track in the endoscopic video sequence.
      By introducing an adaptive weight function in the combination of reference
      current frame tracking with previous-current frame tracking, we enhance the
      tracking performance remarkably. The proposed method is evaluated using an
      endoscopic video of a real ERCP and 3D duodenum model reconstructed from CT data
      of the patient. The result shows real-time performance and robustness of the
      method. 

PMID- 24111447
TI  - Multi-label fast marching and seeded watershed segmentation methods for diagnosis
      of breast cancer cytology.
AB  - Digital cytology plays an increasingly important role in breast cancer diagnosis.
      However, analysis of cytologic images is a very difficult task. Especially,
      nuclei segmentation is extremely challenging. In our work on fully automated
      medical diagnosis system we encountered the problem of densely clustered nuclei.
      We decided to use a segmentation algorithm that is rather rarely found in the
      literature. Multi-label fast marching was applied and compared to well-known and
      extensively used seeded watershed algorithm. In both methods, it is critical to
      determine the appropriate starting points (seeds). The seeds were determined
      using a combination of adaptive thresholding in grayscale, clustering in color
      space and conditional erosion. The proposed segmentation procedure was tested for
      suitability for diagnosis of the cancer. Experiments were conducted on a set of
      450 microscopic images of fine needle biopsies obtained from patients of the
      Regional Hospital in Zielona Gora, Poland. The images were classified as either
      benign or malignant using 84 features extracted from isolated nuclei. Both
      methods gave very promising results and showed that our method is effective and
      can be successfully applied for computer-aided diagnosis system. 

PMID- 24111448
TI  - Towards automatic detection of abnormal retinal capillaries in ultra-widefield-of
      view retinal angiographic exams.
AB  - Retinal capillary abnormalities include small, leaky, severely tortuous blood
      vessels that are associated with a variety of retinal pathologies. We present a
      prototype image-processing system for detecting abnormal retinal capillary
      regions in ultra-widefield-of-view (UWFOV) fluorescein angiography exams of the
      human retina. The algorithm takes as input an UWFOV FA frame and returns the
      candidate regions identified. An SVM classifier is trained on regions traced by
      expert ophthalmologists. Tests with a variety of feature sets indicate that edge
      features and allied properties differentiate best between normal and abnormal
      retinal capillary regions. Experiments with an initial set of images from
      patients showing branch retinal vein occlusion (BRVO) indicate promising area
      under the ROC curve of 0.950 and a weighted Cohen's Kappa value of 0.822. 

PMID- 24111450
TI  - Automated anterior chamber angle localization and glaucoma type classification in
      OCT images.
AB  - To identify glaucoma type with OCT (optical coherence tomography) images, we
      present an image processing and machine learning based framework to localize and
      classify anterior chamber angle (ACA) accurately and efficiently. In digital OCT
      photographs, our method automatically localizes the ACA region, which is the
      primary structural image cue for clinically identifying glaucoma type. Next,
      visual features are extracted from this region to classify the angle as open
      angle (OA) or angle-closure (AC). This proposed method has three major
      contributions that differ from existing methods. First, the ACA localization from
      OCT images is fully automated and efficient for different ACA configurations.
      Second, it can directly classify ACA as OA/AC based on only visual features,
      which is different from previous work for ACA measurement that relies on clinical
      features. Third, it demonstrates that higher dimensional visual features
      outperform low dimensional clinical features in terms of angle closure
      classification accuracy. From tests on a clinical dataset comprising of 2048
      images, the proposed method only requires 0.26s per image. The framework achieves
      a 0.921 +/- 0.036 AUC (area under curve) value and 84.0% +/- 5.7% balanced
      accuracy at a 85% specificity, which outperforms existing methods based on
      clinical features. 

PMID- 24111451
TI  - Adaptive colour transformation of retinal images for stroke prediction.
AB  - Identifying lesions in the retinal vasculature using Retinal imaging is most
      often done on the green channel. However, the effect of colour and single channel
      analysis on feature extraction has not yet been studied. In this paper an
      adaptive colour transformation has been investigated and validated on retinal
      images associated with 10-year stroke prediction, using principle component
      analysis (PCA). Histogram analysis indicated that while each colour channel image
      had a uni-modal distribution, the second component of the PCA had a bimodal
      distribution, and showed significantly improved separation between the retinal
      vasculature and the background. The experiments showed that using adaptive colour
      transformation, the sensitivity and specificity were both higher (AUC 0.73)
      compared with when single green channel was used (AUC 0.63) for the same database
      and image features. 

PMID- 24111452
TI  - Automatic detection of subretinal fluid and sub-retinal pigment epithelium fluid
      in optical coherence tomography images.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      developed countries. Subretinal fluid (SRF) and sub-retinal pigment epithelium
      (sub-RPE) fluid are signs of AMD and can be detected in optical coherence
      tomography images. However, manual detection and segmentation of SRFs and sub-RPE
      fluids are laborious and time consuming. In this paper, a novel pipeline is
      proposed for automatic detection of SRFs and sub-RPE fluids. First, top and
      bottom layers of retina are segmented using a graph cut method. Then, a Split
      Bregman-based segmentation method is used to segment dark regions between layers.
      These segmented regions are considered as potential fluid candidates, on which a
      set of features are generated. After that, a random forest classifier is trained
      to distinguish between the true fluid regions from the falsely detected fluid
      regions. This method shows reasonable performance in a leave-one-out evaluation
      using a dataset from 21 patients. 

PMID- 24111453
TI  - Drusen quantification for early identification of age related macular
      degeneration (AMD) using color fundus imaging.
AB  - Age-related macular degeneration (AMD) is a major cause of visual impairment in
      the elderly and identifying people with the early stages of AMD is important when
      considering the design and implementation of preventative strategies for late
      AMD. Quantification of drusen size and total area covered by drusen is an
      important risk factor for progression. In this paper, we propose a method to
      detect drusen and quantify drusen size along with the area covered with drusen in
      macular region from standard color retinal images. We used combined local
      intensity distribution, adaptive intensity thresholding and edge information to
      detect potential drusen areas. The proposed method detected the presence of any
      drusen with 100% accuracy (50/50 images). For drusen detection accuracy (DDA),
      the segmentations produced by the automated method on individual images achieved
      mean sensitivity and specificity values of 74.94% and 81.17%, respectively. 

PMID- 24111454
TI  - Retinal vessel classification: sorting arteries and veins.
AB  - For the discovery of biomarkers in the retinal vasculature it is essential to
      classify vessels into arteries and veins. We automatically classify retinal
      vessels as arteries or veins based on colour features using a Gaussian Mixture
      Model, an Expectation-Maximization (GMM-EM) unsupervised classifier, and a
      quadrant-pairwise approach. Classification is performed on illumination-corrected
      images. 406 vessels from 35 images were processed resulting in 92% correct
      classification (when unlabelled vessels are not taken into account) as compared
      to 87.6%, 90.08%, and 88.28% reported in [12] [14] and [15]. The classifier
      results were compared against two trained human graders to establish performance
      parameters to validate the success of classification method. The proposed system
      results in specificity of (0.8978, 0.9591) and precision (positive predicted
      value) of (0.9045, 0.9408) as compared to specificity of (0.8920, 0.7918) and
      precision of (0.8802, 0.8118) for (arteries, veins) respectively as reported in
      [13]. The classification accuracy was found to be 0.8719 and 0.8547 for veins and
      arteries, respectively. 

PMID- 24111455
TI  - EEG brain mapping and brain connectivity index for subtypes classification of
      attention deficit hyperactivity disorder children during the eye-opened period.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
      neurological disorders. It is classified by the DSM-IV into three subtypes, i.e.
      1) predominately inattentive type, 2) predominately hyperactive-impulsive type,
      and (3) combined type. In order to make the treatment via the neurofeedback or
      the occupational therapy, quantitative evaluations as well as ADHD subtype
      classification are the important problems to be solved to enhance an alternative
      way to treat ADHD. Hence, in this paper, we systematically classify all of these
      three subtypes by the 19-channel EEG data. Three brain mapping (QEEG) techniques,
      i.e. absolute power of frequency bands, coherence, and phase lag, are employed to
      visualize each type of the ADHD. ADHD children with combined type have deficit in
      delta theta and alpha activity. For the inattentive type, there are excessive
      delta and theta absolute power in the frontal area as well as the excessive
      coherence in beta and high beta frequency bands. For the hyperactivity and
      impulsive type, the behavior is dominated by the slow wave. This information will
      give benefits to the psychiatrist, psychologist, neurofeedback therapist as well
      as the occupational therapist for quantitatively planning and analyzing the
      treatment. 

PMID- 24111456
TI  - Pursuing the flow of information: connectivity between bilateral premotor
      cortices predicts better accuracy in the phonological working memory task.
AB  - Using Magnetoencephalography (MEG) we studied functional connectivity of cortical
      areas during phonological working memory task. Six subjects participated in the
      experiment and their neuronal activity was measured by a 306-channel MEG system.
      We used a modified version of the visual Sternberg paradigm, which required
      subjects to memorize 8 alphabet letters in 2s for a late recall period. We
      estimated functional connectivity of oscillatory regional brain activities during
      the encoding session for each trial of each subject using beamformer source
      reconstruction and Granger causality analysis. Regional brain activities were
      mostly found in the bilateral premotor cortex (Brodmann area (BA) 6: PMC), the
      right dorsolateral prefrontal cortex (BA 9: DLPFC), and the right frontal eye
      field (BA 8). Considering that the left and right PMCs participate in the
      functions of phonological loop (PL) and the visuospatial sketchpad (VS) in the
      Baddeley's model of working memory, respectively, our result suggests that
      subjects utilized either single function or both functions of working memory
      circuitry to execute the task. Interestingly, the accuracy of the task was
      significantly higher in the trials where the alpha band oscillatory activities in
      the bilateral PMCs established functional connectivity compared to those where
      the PMC was not working in conjunction with its counterpart. Similar relationship
      was found in the theta band oscillatory activities between the right PMC and the
      right DLPFC, however in this case the establishment of functional connectivity
      significantly decreased the accuracy of the task. These results suggest that
      sharing the memory load with both PL- and VS- type memory storage circuitries
      contributed to better performance in the highly-demanding cognitive task. 

PMID- 24111457
TI  - Localization of extrastriate body area using functional near-infrared
      spectroscopy and 3D digitizer.
AB  - The extrastriate body area (EBA) is a brain region that responds selectively to
      visual stimuli of human bodies or body parts. Previous studies using functional
      magnetic resonance imaging (fMRI) have shown that EBA occupies a relatively small
      region and varied across subjects in its anatomical location. This study
      investigated whether EBA activity can be detected by functional near-infrared
      spectroscopy (fNIRS) that imposes few physical constraints on the subjects and
      has higher temporal but lower spatial resolutions compared to fMRI. For this
      purpose the subject's brain activity in the occipitotemporal area during
      observation of images of body parts and objects was measured using fNIRS. The
      NIRS optode positions were recorded using a 3D digitizer and mapped onto a
      probabilistic anatomical model. We found that the activity in the
      occipitotemporal region during observation of body stimuli was significantly
      greater than that of object stimuli in 11 out of 16 subjects. The group analyses
      also showed that channels located near the position where the previous studies
      reported EBA activation were more activated during observation of the body
      stimuli compared to the object stimuli. The spatial variance of those channels
      among subjects was relatively small. These results suggest that EBA activity and
      its anatomical location can be sufficiently measured by using fNIRS and a 3D
      digitizer. 

PMID- 24111458
TI  - Measurement of brain activity responded by subjects'own name using EEG.
AB  - Sever motor and intellectual disabilities (SMID) patients can't express their
      feelings with languages. That's why it is important to measure and analyze their
      brain activity. In this study, we tried to investigate the brain response to
      hearing subject's own name of healthy people and one patient with SMID by
      analyzing EEG. The results of time frequency analysis showed the inter trial
      coherence of a patient with SMID at theta oscillation was higher in response to
      SON specifically. On the other hand, that of healthy subjects was not so
      different with that in response to control condition. These results might reflect
      of the difference of lexical semantic process between the patient and healthy
      subjects. 

PMID- 24111459
TI  - Hybrid SSVEP-motion visual stimulus based BCI system for intelligent wheelchair.
AB  - This paper proposes the hybrid BCI modalities for wheelchair control by taking
      into account weakness of the current BCI systems. The idea is to combine two
      hybrid BCI systems with the intelligent wheelchair for three states, i.e. normal,
      fatigue, and emergency states. First system is the hybrid steady state visual
      evoked potential (SSVEP) and alpha rhythm BCI which is designed to use in the
      normal state. Second system is the hybrid motion visual stimulus and alpha rhythm
      which can be employed during the fatigue state (after using the first system).
      For the experiment, subjects are asked to perform SSVEP system for 30 minutes
      (until the fatigue states occur). Then, the subjects will be asked to perform the
      hybrid motion visual stimulus and alpha rhythm testing. The accuracy of the
      proposed system during fatigue state is approximately 85.62%. With this idea, BCI
      controlled wheelchair can be efficiently employed in reality. 

PMID- 24111460
TI  - Regularization using similarities of signals observed in nearby sensors for
      feature extraction of brain signals.
AB  - In order to solve uncertainty of spatial weights learned with small amount of
      training samples for feature extraction from brain signals, a regularization
      using similarity of signals observed in sensors that are located near each other
      is proposed. Deriving the regularization is begun defining a distance between the
      sensors. Under the distance, the proposed regularization works so that the
      spatial weights extracts similar signals in the nearby sensors. The proposed
      regularization is applied to the well known common spatial pattern (CSP) method
      that finds spatial weights for EEG based brain machine interface. In the
      classification experiment using a dataset of EEG signals during motor imagery,
      the proposed method achieved maximum improvement by 28% in the classification
      accuracy over the standard CSP in a setting of even when only five samples are
      used. 

PMID- 24111461
TI  - Low-complexity intrauterine pressure monitoring by Teager energy estimation.
AB  - Monitoring the progression of maternal uterine activity provides important
      prognostic information during pregnancy and parturition. Currently used methods,
      however, are unsuitable for long-term observation of uterine activity. The
      abdominally measured electrohysterogram (EHG) provides a non-invasive alternative
      to the existing methods for long-term ambulatory uterine contraction monitoring.
      A new EHG signal analysis method for intrauterine pressure (IUP) estimation based
      on the Teager energy estimate is proposed. The new method is compared to existing
      methods from the literature in terms of estimation accuracy and computational
      complexity. An accurate IUP estimate, with a complexity up to 40 times lower than
      that of algorithms from the literature is obtained. Therefore, the proposed
      method offers a valuable new option for long-term uterine monitoring. 

PMID- 24111462
TI  - Prediction of labor using non-invasive Laplacian EHG recordings.
AB  - Non-invasive electrohysterogram (EHG) recordings could be used as an alternative
      technique for monitoring uterine dynamics. Bipolar recordings of EHG have proven
      to provide valuable information to predict labor. Recently it has been stated
      that uterine EHG bursts could also be identified in Laplacian recordings on
      abdominal surface. Taking into account that Laplacian potential technique permits
      to acquire more localized electrical activity than conventional recordings; these
      recordings could also be helpful for deducing uterine contraction efficiency. The
      aim of this paper is to examine the feasibility of Laplacian potential EHG
      recording for labor prediction and to compare it with monopolar recordings. To
      this purpose, a total of 42 EHG recordings were acquired from women of similar
      gestational age: 29 antepartum patients, and 13 patients in labor. Then linear
      and non-linear classifiers have been implemented using EHG burst parameters as
      input features. Experimental results show significant differences in temporal and
      spectral parameters in both monopolar and Laplacian potential recordings between
      the two groups. In addition, support vector machine based classifier achieved an
      accuracy of 93% for labor prediction for monopolar recordings, 92% for bipolar
      recordings and 91% for Laplacian potential. 

PMID- 24111463
TI  - Characterization of EHG contractions at term labor by nonlinear analysis.
AB  - Uterine electromyogram on the abdomen of pregnant women (electrohysterogram, EHG)
      plays an interesting role to evaluate possible risks to the binomial mother
      fetus. In this sense, the present study explored the characterization of
      contractions by EHG during active phase of labor at term in a population at low
      risk. The goal was to investigate the differences in the contractions generated
      by women that evolve labor to a vaginal delivery (group 1) to those associated
      with caesarean section (group 2). Abdominal signals were acquired using Ag-AgCl
      electrodes in a bipolar configuration and the EHG was obtained by band-pass
      filtering in the range of 0.3 to 4 Hz. Sample entropy (SampEn) was used to
      calculate the irregularity of manually selected contractions of the EHG time
      series. The results showed that it is plausible to discriminate contractions from
      both groups as the average SampEn was 2.1359 with a standard deviation of 0.0583
      for group 1 (N=8), while for group 2 (N=8) was 2.0352 with standard deviation of
      0.0946; it was found significant statistical difference between groups as p was
      0.046. Consequently, the nonlinear analysis via SampEn of EHG could provide an
      index to evaluate the quality of the active phase labor at term. 

PMID- 24111465
TI  - Preliminary global sensitivity analysis of a uterine electrical activity model.
AB  - A comprehensive multiscale model of the uterine muscle electrical activity would
      permit understanding the important link between the genesis and evolution of the
      action potential at the cell level and the process leading to labor.
      Understanding this link can open the way to more effective tools for the
      prediction of labor and prevention of preterm delivery. 

PMID- 24111464
TI  - Ultrasound analysis of the uterine wall movement for improved
      electrohysterographic measurement and modeling.
AB  - During pregnancy, analysis of the electrohysterogram (EHG), which measures the
      uterine electrical activity, can provide a fundamental contribution for the
      assessment of uterine contractions and the diagnosis of preterm labor. However,
      several aspects concerning uterine physiology and its link with EHG measurements
      are still unclear. As a consequence, the EHG is not yet part of the clinical
      practice. There is general consensus that modeling and analysis of the EHG can be
      improved only by understanding and integrating the main properties of the uterine
      physiology at different levels, e:g:, cellular, tissue, and organ, and of
      different nature, e:g:, electrical, mechanical, and structural. In this study, we
      use transabdominal ultrasound (US) measurements to investigate the mechanical
      changes that the uterus undergoes during pregnancy under the effect of
      contractions. We refer to this measurement as mechanohysterogram. Analysis of the
      mechanohysterogram highlights, for the first time, two phenomena that can
      influence EHG signal interpretation, namely, changes in uterine wall thickness
      during contractions and respiration-induced uterine wall movements. Our results
      suggest that these phenomena can affect the interpretation of the EHG and should
      therefore be taken into account for accurate modeling and assessment of the
      uterine electrical activity. 

PMID- 24111466
TI  - Windowed multivariate autoregressive model improving classification of labor vs.
      pregnancy contractions.
AB  - Analyzing the propagation of uterine electrical activity is poised to become a
      powerful tool in labor detection and for the prediction of preterm labor. Several
      methods have been proposed to investigate the relationship between signals
      recorded externally from several sites on the pregnant uterus. A promising recent
      method is the multivariate autoregressive (MVAR) model. In this paper we proposed
      a windowed (time varying) version of the multivariate autoregressive model,
      called W-MVAR, to investigate the connectivity between signals while still
      respecting their non-stationary characteristics. The proposed method was tested
      on synthetic signals as well as applied to real signals. The comparison between
      the two methods on synthetic signals showed the superiority of W-MVAR to detect
      connectivity even if it is non-stationary. The application of W-MVAR on
      multichannel real uterine signals show that the proposed method is a good tool to
      distinguish non-labor and labor signals. These results are very promising and can
      very possibly have important clinical applications in labor detection and preterm
      labor prediction. 

PMID- 24111467
TI  - A multiscale model of the electrohysterogram the BioModUE_PTL project.
AB  - The electrohysterogram (EHG) is a promising means of monitoring pregnancy and of
      detecting a risk of preterm labor. To improve our understanding of the EHG as
      well as its relationship with the physiologic phenomena involved in uterine
      contractility, we plan to model these phenomena in terms of generation and
      propagation of uterine electrical activity. This activity can be realistically
      modeled by representing the principal ionic dynamics at the cell level, the
      propagation of electrical activity at the tissue level and then the way it is
      reflected on the skin surface through the intervening tissue. We present in this
      paper the different steps leading to the development and validation of a
      biophysics based multiscale model of the EHG, going from the cell to the
      electrical signal measured on the abdomen. 

PMID- 24111468
TI  - The influences of emotional intensity for happiness and sadness on walking.
AB  - Walking is one of the most common activities that we perform every day. Even if
      the main goal of walking is to move from one place to another place, walking can
      also convey emotional clues in social context. Those clues can be used to improve
      interactions or any messages we want to express. However, there are not many
      studies on the effects of the intensity of the emotions on the walking. In this
      paper, the authors propose to assess the differences between the expression of
      emotion regarding the expressed intensity (low, middle, high and exaggerated). We
      observed two professional actors perform emotive walking, with different
      intensities and we analyzed the recorded data. For each emotion, we analyzed
      characteristic features which can be used in the future to model gait patterns
      and to recognize emotions from the gait parameters. Additionally, we found
      characteristics which can be used to create new emotion expression for our biped
      robot Kobian, improving the human-robot interaction. 

PMID- 24111469
TI  - Using single leg standing time to predict the fall risk in elderly.
AB  - In clinical evaluation, we used to evaluate the fall risk according to elderly
      falling experience or the balance assessment tool. Because of the tool
      limitation, sometimes we could not predict accurately. In this study, we first
      analyzed 15 healthy elderly (without falling experience) and 15 falling elderly
      (1~3 time falling experience) balance performance in previous research. After 1
      year follow up, there was only 1 elderly fall down during this period. It seemed
      like that falling experience had a ceiling effect on the falling prediction. But
      we also found out that using single leg standing time could be more accurately to
      help predicting the fall risk, especially for the falling elderly who could not
      stand over 10 seconds by single leg, and with a significant correlation between
      the falling experience and single leg standing time (r = -0.474, p = 0.026). The
      results also showed that there was significant body sway just before they falling
      down, and the COP may be an important characteristic in the falling elderly
      group.

PMID- 24111470
TI  - Effects of light finger touch to the upper legs on postural sway and muscle
      activity during quiet standing.
AB  - The purpose of the present study was to investigate the effects of light finger
      touch (LT) to one's own body on postural sway and ankle muscle activity during
      quiet standing. In the first part of the present study, 24 healthy men (19 +/- 1
      years) stood upright with their eyes closed on a pneumatic balance disk under 3
      different conditions. In the first condition, the participants kept their hands
      in loose fists, and contact between the fingers/palms and the legs was avoided.
      In the second condition, the participants touched the lateral sides of upper legs
      lightly (without applying force for mechanical support) with all fingers. In the
      third condition, the participants again held their hands in loose fists. Postural
      sway was significantly decreased during second condition compared to first
      condition. Further, it also tended to decrease in third condition (P = 0.08). The
      second part of the present study was designed to investigate the mechanisms
      underlying the association between postural sway and LT by analyzing
      electromyographic data. Data were obtained from 12 healthy men (20 +/- 1 years).
      During quiet stance on the stable surface, soleus activity did not significantly
      change by LT. However, tibialis-anterior activity significantly decreased with
      LT. These results suggest that LT to the upper part of one's own legs decreases
      postural sway (during and after touching) during a still stance by decreasing co
      activation of the ankle muscles.

PMID- 24111471
TI  - Generalization of a muscle-reflex control model to 3D walking.
AB  - The neural controller that generates human locomotion can currently not be
      measured directly, and researchers often resort to forward dynamic simulations of
      the human neuromuscular system to propose and test different controller
      architectures. However, most of these models are restricted to locomotion in the
      sagittal plane, which limits the ability to study and compare proposed neural
      controls for 3D-related motions. Here we generalize a previously identified
      reflex control model for sagittal plane walking to 3D locomotion. The
      generalization includes additional degrees of freedom at the hips in the lateral
      plane, their actuation and control by hip abductor and adductor muscles, and 3D
      compliant ground contact dynamics. The resulting 3D model of human locomotion
      generates normal walking while producing human-like ground reaction forces and
      moments, indicating that the proposed neural controller based on muscle reflexes
      generalizes well to 3D locomotion. 

PMID- 24111472
TI  - Ageing effects on medio-lateral balance during walking with increased and
      decreased step width.
AB  - The current study used falls direction to categorize falls and explore age
      related effects on the biomechanics of medio-lateral balance control. Minimum
      lateral margin (MLM) was defined as the critical swing phase event where the
      medio-lateral length between center of mass (CoM) and stance heel became minimum
      and accordingly, any lateral balance perturbation at MLM was considered to
      increase the risk of balance loss lateral to the stance foot. Lateral center of
      pressure (CoP) displacement from toe-off to MLM was also monitored to assess the
      risk of medio-lateral balance perturbation. Gait testing involving 30 young and
      26 older male subjects was conducted under the three step width conditions:
      preferred and +/- 50% wider and narrower. For an overall description of gait,
      spatio-temporal parameters were also obtained. Typical ageing effects on spatio
      temporal parameters such as lower step velocity, shorter step length and
      prolonged double support time were found, emerging most clearly in narrower,
      followed by wider and least in preferred width walking. MLM and CoP lateral
      displacement were not differentiated between the two age groups, but older adults
      demonstrated significantly more variable MLM and CoP in their non-dominant limb
      when walking with non-preferred widths. Variability of step width reduced in
      increased and decreased step width conditions while MLM and CoP variability
      increased, suggesting less consistent medio-lateral CoM control despite
      consistent foot control in altered width conditions. In summary, older adults
      were found to have less consistent control of CoM with respect to the non
      dominant stance foot when walking with narrower and wider widths possibly due to
      more variable medio-lateral CoP control.

PMID- 24111473
TI  - Using a foot mounted accelerometer to detect changes in gait patterns.
AB  - The purpose of this study is to investigate how data from a foot mounted
      accelerometer can be used to detect motor pattern healthy subjects performed
      walking trails under two different conditions; normal and stiff ankle walking.
      Lower body kinematic data were collected as well as accelerometer data from both
      feet. An algorithm is presented which quantifies relevant swing phase
      characteristics from the foot accelerometer. Peak total acceleration during
      initial swing was significantly higher in the stiff ankle condition (M = 33.10,
      SD = 5.12) than in the normal walking condition (M = 29.47, SD = 5.75; t(7) =
      4.32, p = .003, two-tailed). There was a large effect size (eta squared = 0.853).
      Time between peak acceleration during initial swing to foot strike was
      significantly shorter in the stiff ankle condition (M = 0.42, SD = 0.02) than in
      the normal condition (M = 0.44, SD = 0.03; t(7) = -2.54, p = .039, two- tailed).
      There was a large effect size (eta squared = 0.693). Simple to process metrics
      from tri-axial accelerometer data on the foot show potential to detect changes in
      ankle kinematic patterns. 

PMID- 24111474
TI  - An analysis of leg joint synergy during backward walking.
AB  - Grasso et al. (1998) proposed the hypothesis that motor commands for the backward
      walking is designed so as to reproduce the reversal motion of forward walking. In
      this study, we analyzed the leg joint synergy in backward walking by the UCM
      analysis and compared the results with the time reversal profile of the synergy
      in forward walking. Some similarities between them were observed, e.g., the body
      posture is controlled by utilizing joint synergy during double support phase.
      However, differences were also observed during swing phase, e.g., at touch down
      at the end of swing phase the joint synergy is utilized to adjust the foot
      position in backward walking, contrary in forward walking the synergy is not
      utilized but the variance of joint angles are suppressed. The results indicate
      that the backward walking is not a reversal motion of forward walking, but
      planned independently of forward walking. 

PMID- 24111475
TI  - Recognition of correct finger placement for photoplethysmographic imaging.
AB  - In mobile health applications, non-expert users often perform the required
      medical measurements without supervision. Therefore, it is important that the
      mobile device guides them through the correct measurement process and
      automatically detects potential errors that could impact the readings. Camera
      oximetry provides a non-invasive measurement of heart rate and blood oxygen
      saturation using the camera of a mobile phone. We describe a novel method to
      automatically detect the correct finger placement on the camera lens for camera
      oximetry. Incorrect placement can cause optical shunt and if ignored, lead to low
      quality oximetry readings. The presented algorithm uses the spectral properties
      of the pixels to discriminate between correct and incorrect placements.
      Experimental results demonstrate high mean accuracy (99.06%), sensitivity
      (98.06%) and specificity (99.30%) with low variability. By sub-sampling pixels,
      the computational cost of classifying a frame has been reduced by more than three
      orders of magnitude. The algorithm has been integrated in a newly developed
      application called OxiCam where it provides real-time user feedback. 

PMID- 24111476
TI  - A novel data-mining platform leveraging social media to monitor outcomes of
      Januvia.
AB  - A novel data-mining method was developed to gauge the experiences of the diabetes
      mellitus drug Januvia. Self-organizing maps were used to analyze forum posts
      numerically to infer user opinion of drug Januvia. Graph theory was used to
      discover influential users. The result is a word list compilation correlating
      positive and negative word cluster groups and a web of influential users on
      Januvia. The implications could open new research avenues into rapid data
      collection, feedback, and analysis that would enable improved solutions for
      public health. 

PMID- 24111477
TI  - Telehealth streams reduction based on pattern recognition techniques for events
      detection and efficient storage in EHR.
AB  - This work proposes a framework for telehealth streams analysis, founded on a
      pattern recognition technique that evaluates the similarity between multi
      sensorial biosignals. The strategy combines the Haar wavelet with the Karhunen
      Loeve transforms to describe biosignals by means of a reduced set of parameters.
      These, that reflect the dynamic behavior of the biosignals, can support the
      detection of relevant clinical conditions. Moreover, the simplicity and fast
      execution of the proposed approach allow its application in real-time operation,
      as well as provide a practical way to manage historical electronic health
      records: i) common and uncommon behaviors can be distinguished; ii) the creation
      of different models, tailored to specific conditions can be efficiently stored.
      The efficiency of the methodology is assessed through its performance analysis,
      namely by computing the required number of operations and the compression rate.
      Its effectiveness is evaluated in the prediction of decompensation episodes using
      biosignals daily collected in the myHeart study (blood pressure, weight,
      respiration and heart rates). 

PMID- 24111478
TI  - A telehealth system for Parkinson's disease remote monitoring. The PERFORM
      approach.
AB  - This paper summarizes the experience and the lessons learned from the European
      project PERFORM (A sophisticated multi-parametric system FOR the continuous
      effective assessment and monitoring of motor status in Parkinson's disease and
      other neurodegenerative diseases). PERFORM is aimed to provide a telehealth
      system for the remote monitoring of Parkinson's disease patients (PD) at their
      homes. This paper explains the global experience with PERFORM. It summarizes the
      technical performance of the system and the feedback received from the patients
      in terms of usability and wearability. 

PMID- 24111479
TI  - A low-cost scalable solution for digitizing analog X-rays with applications to
      rural healthcare.
AB  - In this paper, we present a low-cost scalable solution for digitizing analog X
      ray images with the goal of improving diagnostics in rural and remote areas, in
      addition to having potential applications in disaster healthcare. Our solution
      attempts to capitalize on the rapid gains made in cellular communication and
      mobile technologies. The proposed mobile application lets the user digitally
      acquire the analog X-ray image and apply enhancement operations to it. A novel
      nonlinear technique for X-ray image enhancement has been proposed and implemented
      in the application. Additionally, several standard enhancement techniques have
      also been implemented. A proof-of-concept of the proposed solution is
      demonstrated with an Android application running on a smartphone. Results from
      real-world data collected at a semi-urban hospital in India are presented. The
      Android application has been made available online at the fifth authors'
      homepage. 

PMID- 24111480
TI  - A wearable healthcare system for cardiac signal monitoring using conductive
      textile electrodes.
AB  - Accurate cardiac signal monitoring feasible for long-term monitoring is important
      for a practical, cost-effective health monitoring system. In this study, we
      propose a wearable healthcare system based on conductive fabric-based electrodes
      allowing monitoring of electrocardiogram (ECG) waveforms and demonstrated the
      potential for arrhythmia detection using the system. The measurement system uses
      conductive fabric-based electrodes arranged in a modified bipolar electrode
      configuration on the chest area of the patient. An adaptive impulse correlation
      filter (AICF) algorithm and a band pass filter to enable accurate R-peak
      detection in noisy environments. 

PMID- 24111481
TI  - Airways in out-of-hospital cardiac arrest: systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the differences in survival for out-of-hospital advanced
      airway intervention (AAI) compared with basic airway intervention (BAI) in
      cardiac arrest. BACKGROUND: AAI is commonly utilized in cardiac arrest in the out
      of-hospital setting as a means to secure the airway. Observational studies and
      clinical trials of AAI suggest that AAI is associated with worse outcomes in
      terms of survival. No controlled trials exist that compares AAI to BAI. METHODS:
      We conducted a bias-adjusted meta-analysis on 17 observational studies. The
      outcomes were survival, short-term (return of spontaneous circulation and to
      hospital admission), and longer-term (to discharge, to one month survival). We
      undertook sensitivity analyses by analyzing patients separately: those who were
      16 years and older, nontrauma only, and attempted versus successful AAI. RESULTS:
      This meta-analysis included 388,878 patients. The short-term survival for AAI
      compared to BAI were overall OR 0.84(95% CI 0.62 to 1.13), for endotracheal
      intubation (ETI) OR 0.79 (95% CI 0.54 to 1.16), and for supraglottic airways
      (SGA) OR 0.59 (95% CI 0.39 to 0.89). Long-term survival for AAI were overall OR
      0.49 (95% CI 0.37 to 0.65), for ETI OR 0.48 (95% CI 0.36 to 0.64), and for SGA OR
      0.35 (95% CI 0.28 to 0.44). Sensitivity analyses shows that limiting analyses to
      adults, non-trauma victims, and instances where AAI was both attempted and
      successful did not alter results meaningfully. A third of all studies did not
      adjust for any other confounding factors that could impact on survival.
      CONCLUSIONS: This meta-analysis shows decreased survival for AAIs used out-of
      hospital in cardiac arrest, but are likely biased due to confounding, especially
      confounding by indication. A properly conducted prospective study or a controlled
      trial is urgently needed and are possible to do.

PMID- 24111482
TI  - Cancer talk on twitter: community structure and information sources in breast and
      prostate cancer social networks.
AB  - This study suggests taking a social networks theoretical approach to predict and
      explain patterns of information exchange among Twitter prostate and breast cancer
      communities. The authors collected profiles and following relationship data about
      users who posted messages about either cancer over 1 composite week. Using social
      network analysis, the authors identified the main clusters of interconnected
      users and their most followed hubs (i.e., information sources sought). Findings
      suggest that users who populated the persistent-across-time core cancer
      communities created dense clusters, an indication of taking advantage of the
      technology to form relationships with one another in ways that traditional one-to
      many communication technologies cannot support. The major information sources
      sought were very specific to the community health interest and were grassroots
      oriented (e.g., a blog about prostate cancer treatments). Accounts associated
      with health organizations and news media, despite their focus on health, did not
      play a role in these core health communities. Methodological and practical
      implications for researchers and health campaigners are discussed. 

PMID- 24111485
TI  - Coordination equilibria between seven- and five-coordinate iron(II) complexes.
AB  - Octahedral, tetrahedral, and square planar geometries are the most often
      encountered coordination geometries for transition metal complexes. In certain
      cases, coordination equilibria can exist between different geometries, such as
      between six- and four-coordinate geometries in nickel(II) complexes, which were
      discovered half a century ago. Here, we present the first examples of a seven
      five coordination equilibrium. Extensive spectroscopic studies in solution have
      provided evidence for a dynamic equilibrium between two iron(II) complexes, one
      with a seven-coordinate pentagonal bipyramidal geometry and one with a five
      coordinate trigonal bipyramidal geometry. 

PMID- 24111486
TI  - Predictors of sustainability for community-managed handpumps in sub-Saharan
      Africa: evidence from Liberia, Sierra Leone, and Uganda.
AB  - Rural water supply sustainability has remained an enduring policy challenge in
      sub-Saharan Africa for decades. Drawing on the largest data set assembled on
      rural water points in sub-Saharan Africa to date, this paper employs logistic
      regression analyses to identify operational, technical, institutional, financial,
      and environmental predictors of functionality for over 25 000 community-managed
      handpumps in Liberia, Sierra Leone, and Uganda. Risk factors significantly
      associated with nonfunctionality across all three countries were (a) system age,
      (b) distance from district/county capital, and (c) absence of user fee
      collection. In at least one of the three countries, other variables found to have
      significant multivariable adjusted associations with functionality status
      included well type, handpump type, funding organization, implementing
      organization, spare parts proximity, availability of a handpump mechanic, regular
      servicing, regular water committee meetings, women in key water committee
      positions, rainfall season, and perceived water quality. While the findings
      reinforce views that a multifaceted range of conditions is critical for the
      sustainability of community-managed handpumps, they also demonstrate that these
      factors remain absent from a high proportion of cases. Governments and
      development partners must significantly strengthen postconstruction support for
      operation and maintenance systems, and greater efforts are needed to test and
      evaluate alternative models for managing handpump water supplies. 

PMID- 24111487
TI  - Understanding scanning tunneling microscopy contrast mechanisms on metal oxides:
      a case study.
AB  - A comprehensive analysis of contrast formation mechanisms in scanning tunneling
      microscopy (STM) experiments on a metal oxide surface is presented with the
      oxygen-induced (2?2*?2)R45 degrees  missing row reconstruction of the Cu(100)
      surface as a model system. Density functional theory and electronic transport
      calculations were combined to simulate the STM imaging behavior of pure and
      oxygen-contaminated metal tips with structurally and chemically different apexes
      while systematically varying bias voltage and tip-sample distance. The resulting
      multiparameter database of computed images was used to conduct an extensive
      comparison with experimental data. Excellent agreement was attained for a large
      number of cases, suggesting that the assumed model tips reproduce most of the
      commonly encountered contrast-determining effects. Specifically, we find that
      depending on the bias voltage polarity, copper-terminated tips allow selective
      imaging of two structurally distinct surface Cu sites, while oxygen-terminated
      tips show complex contrasts with pronounced asymmetry and tip-sample distance
      dependence. Considering the structural and chemical stability of the tips reveals
      that the copper-terminated apexes tend to react with surface oxygen at small tip
      sample distances. In contrast, oxygen-terminated tips are considerably more
      stable, allowing exclusive surface oxygen imaging at small tip-sample distances.
      Our results provide a conclusive understanding of fundamental STM imaging
      mechanisms, thereby providing guidelines for experimentalists to achieve
      chemically selective imaging by properly selecting imaging parameters. 

PMID- 24111488
TI  - Host defense peptides: general overview and an update on their activity against
      Chlamydia spp.
AB  - Chlamydiae are obligate intracellular bacteria that cause serious diseases in a
      wide range of hosts. Chlamydia trachomatis is one of the leading sexually
      transmitted pathogens in the world. Because vaccines are not currently available,
      effective drugs are essential. In both animals and humans, chlamydial infections
      are often treated with tetracycline or its derivatives. A stable tetracycline
      resistant phenotype was described in Chlamydia suis strains from pigs in the USA
      and in Europe. In humans, there are reports of tetracycline treatment failure and
      the in vitro adaptability of C. trachomatis to evolve to antibiotic resistance
      has been described, suggesting the pressing need to search for alternative and
      effective classes of antimicrobial drugs. Host defense peptides (HDPs) are known
      as direct antimicrobial agents as well as innate immune modulators. Being active
      against multidrug-resistant bacteria, HDPs are attractive candidates as templates
      for new drugs. A number of studies evaluated the activity of natural and
      synthetic HDPs against Chlamydia spp., showing C. trachomatis to be the most
      sensitive among chlamydia species tested. Protegrins and alpha-helical peptides
      were the most active among the HDPs assessed. 

PMID- 24111490
TI  - Is neuromyelitis optica with advanced age of onset a paraneoplastic disorder?
AB  - BACKGROUND: Neuromyelitis optica (NMO) antibodies are commonly found in patients
      with NMO, a relapsing CNS inflammatory disorder. Recent evidence suggests that
      the NMO antibody may be a paraneoplastic marker. We evaluated this possibility
      using a health system-wide electronic medical record (EMR), allowing assessment
      of neoplasm both before and after the assessment of NMO seropositivity.
      DESIGN/METHODS: An automated search of the Cleveland Clinic EMR was performed to
      identify patients with NMO serology testing (since 2006). Demographic, clinical,
      and imaging data were collected, including malignancy history. RESULTS: A total
      of 41 patients NMO seropositive subjects were found. Average age at first
      clinical symptom was 38.7 years (SD 15.1), and 33 (80.5%) patients met formal
      criteria for NMO. Six malignancies were identified in five NMO seropositive
      patients (12.2%; age 48.7 years [SD 12.4] at presentation of NMO). Cancers
      included breast carcinoma (three cases), lymphoma, cervical carcinoma and
      leiomyosarcoma. The timing of malignancy diagnosis varied from 15 years prior to
      14 years after the onset of neurologic symptoms. Among seropositive patients over
      age 50 years at the time of this review, malignancy was seen in 5/25 patients
      (20%). All five subjects fulfilled NMO clinical criteria. CONCLUSIONS: A high
      prevalence of malignancy was found in NMO seropositive patients, although the
      sample size was small. These observations support the possibility of NMO as a
      paraneoplastic marker. If further studies confirm this relationship, clinicians
      may consider malignancy screening in individuals seropositive for NMO,
      particularly those over the age of 48.

PMID- 24111489
TI  - Fundamental reaction pathway for peptide metabolism by proteasome: insights from
      first-principles quantum mechanical/molecular mechanical free energy
      calculations.
AB  - Proteasome is the major component of the crucial non-lysosomal protein
      degradation pathway in the cells, but the detailed reaction pathway is unclear.
      In this study, first-principles quantum mechanical/molecular mechanical free
      energy calculations have been performed to explore, for the first time, possible
      reaction pathways for proteasomal proteolysis/hydrolysis of a representative
      peptide, succinyl-leucyl-leucyl-valyl-tyrosyl-7-amino-4-methylcoumarin (Suc-LLVY
      AMC). The computational results reveal that the most favorable reaction pathway
      consists of six steps. The first is a water-assisted proton transfer within
      proteasome, activating Thr1-O(gamma). The second is a nucleophilic attack on the
      carbonyl carbon of a Tyr residue of substrate by the negatively charged Thr1
      O(gamma), followed by the dissociation of the amine AMC (third step). The fourth
      step is a nucleophilic attack on the carbonyl carbon of the Tyr residue of
      substrate by a water molecule, accompanied by a proton transfer from the water
      molecule to Thr1-N(z). Then, Suc-LLVY is dissociated (fifth step), and Thr1 is
      regenerated via a direct proton transfer from Thr1-N(z) to Thr1-O(gamma).
      According to the calculated energetic results, the overall reaction energy
      barrier of the proteasomal hydrolysis is associated with the transition state
      (TS3(b)) for the third step involving a water-assisted proton transfer. The
      determined most favorable reaction pathway and the rate-determining step have
      provided a reasonable interpretation of the reported experimental observations
      concerning the substituent and isotopic effects on the kinetics. The calculated
      overall free energy barrier of 18.2 kcal/mol is close to the experimentally
      derived activation free energy of ~18.3-19.4 kcal/mol, suggesting that the
      computational results are reasonable. 

PMID- 24111491
TI  - Formation of N-heterocyclic carbene-boryl radicals through electrochemical and
      photochemical cleavage of the B-S bond in N-heterocyclic carbene-boryl sulfides.
AB  - The B-S bond in N-heterocyclic carbene (NHC)-boryl sulfides can be cleaved
      homolytically to NHC-boryl or NHC-thioboryl and thiyl radicals using light,
      either directly around 300 nm or with a sensitizer at a longer wavelength (>340
      nm). In contrast, the electrochemical reductive cleavage of the B-S bond is
      difficult. This easy photolytic cleavage makes the NHC-boryl sulfides good type I
      photopolymerization initiators for the polymerization of acrylates under air. 

PMID- 24111492
TI  - How does change occur following a theoretically based self-management
      intervention for type 2 diabetes.
AB  - The purpose of this study was to test the extent that constructs from two
      theoretical models (self-regulatory theory and social cognitive theory) mediated
      change in outcomes following a self-management intervention. One hundred and
      twenty four individuals with type 2 diabetes who had participated in a randomised
      controlled trial of a diabetes self-management programme were analysed for the
      extent that illness beliefs and self-efficacy mediated change in self-management
      behaviours and illness specific quality of life. Exercise specific self-efficacy
      significantly mediated change in exercise at three months (B = .03; .01, p < .05)
      while monitoring specific self-efficacy mediated change in monitoring behaviour
      at both three (B = .04; .01, p < .01) and nine months follow-up (B = 5.97; 1.01,
      p < .01). Belief in control over diabetes mediated change in illness specific
      quality of life at three months (B = -.07; .28, p < .05) and nine months (B =
      .79; .28, p < .01) follow-ups, as well as change in exercise behaviour at
      immediately post-intervention (B = -.12; .17, p < .05). Behaviour-specific self
      efficacy may have a stronger role in mediating self-management behaviours than
      illness beliefs; however, belief in control over diabetes may be important to
      manipulate for change in quality of life. This suggests different theoretical
      constructs may mediate change dependent on outcome.

PMID- 24111493
TI  - Serum uric acid level is associated with the development of microalbuminuria in
      Korean men.
AB  - BACKGROUND: Elevated serum uric acid (UA) could be a risk factor for
      hypertension, type 2 diabetes mellitus and cardiovascular disease. In addition,
      elevated serum UA may be associated with impaired renal function. However, it is
      unclear whether elevated serum UA is a cause of microalbuminuria or not.
      Therefore, we performed a prospective cohort study of the temporal relationship
      between baseline elevated serum UA and the development of microalbuminuria in
      Korean men. DESIGN AND METHODS: A microalbuminuria-free cohort of 1743 healthy
      Korean men, who had their urine albumin-creatinine ratio (UACR) calculated for a
      medical check-up programme in 2005, was followed until 2010. Microalbuminuria was
      defined as a urine albumin-creatinine ratio between 30 and 300 MUg/mg. Cox
      proportional hazards model was performed. RESULTS: During 5884.6 person-years of
      follow-up, 96 incident cases of microalbuminuria developed between 2006 and 2010.
      After adjusting for multiple covariates, the hazard ratios (95% confidence
      intervals) for incident microalbuminuria when comparing the second tertile to the
      third tertile of serum UA levels vs. the first tertile were 1.52 (0.86-2.70) and
      2.27 (1.30-3.98), respectively (P for trend = 0.005). CONCLUSION: Elevated serum
      UA level was independent risk factor for the development of microalbuminuria
      during a 5-year follow-up in Korean men.

PMID- 24111494
TI  - Clustering of body composition, blood pressure and physical activity in
      Portuguese families.
AB  - AIM: The purposes of this study were: (i) to identify familial resemblances in
      body fat, blood pressure (BP) and total physical activity (TPA); (ii) to estimate
      the magnitude of their genetic and environmental influences; and (iii) to
      investigate shared familial aggregation among these phenotypes. SUBJECTS AND
      METHODS: The sample comprised 260 nuclear families from Portugal. Body fat was
      assessed by bioelectrical impedance. BP was measured by an oscillometric device.
      TPA was estimated by the Baecke questionnaire. Familial correlation analyses were
      performed using Generalized Estimating Equations. Quantitative genetic modelling
      was used to estimate maximal heritability, genetic and environmental
      correlations. RESULTS: Familial intra-trait correlations ranged from 0.15-0.38.
      Genetic and common environmental factors explained from 30%--44% of fat mass
      depots and BP and 24% of TPA. Genetic correlations were significant between BP
      and the fat mass traits (p < 0.05). Environmental correlations were statistically
      significant between diastolic BP and total body fat, trunk fat and arm fat (p <
      0.05) and TPA and other phenotypes. CONCLUSIONS: The results suggest familial
      resemblance in the variation of body fat, BP and TPA, showing partial pleiotropic
      effects in the variation in body fat phenotypes and BP. TPA only shares common
      environmental influences with BP and body fat traits.

PMID- 24111495
TI  - Role of ADAMTS13 in the management of thrombotic microangiopathies including
      thrombotic thrombocytopenic purpura (TTP).
AB  - The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other
      thrombotic microangiopathies (TMAs) can often be similar. The role of a
      disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
      (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be
      debated in a few studies. We report the experience of our single-centre academic
      institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange
      (PLEX). Patients presenting to our institution with thrombotic microangiopathy
      (60 patients) between January 2006 and December 2012 were divided into two groups
      based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity
      <10% were included in the TTP (n = 30) cohort while patients with activity >11%
      were classified as 'other microangiopathies' (TMA, n = 30). PLEX was only
      initiated in patients with a high likelihood of TTP and discontinued when the
      baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency
      (TTP group) showed significant presenting differences: lower platelet counts,
      less renal dysfunction, higher presence of neurological abnormalities, and
      greater haemolysis markers as compared to non-deficient patients (TMA group).
      Most importantly, patients without severe ADAMTS13 deficiency were safely managed
      without increased mortality despite receiving no PLEX or discontinuing PLEX after
      a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13
      can be used to diagnose TTP and guide appropriate PLEX therapy.

PMID- 24111496
TI  - Cinacalcet treatment decreases plasma fibroblast growth factor 23 concentration
      in haemodialysed patients with chronic kidney disease and secondary
      hyperparathyroidism.
AB  - OBJECTIVE: Recent clinical studies suggest that fibroblast growth factor 23
      (FGF23) is important in the pathogenesis of calcium-phosphate abnormalities in
      patients with chronic kidney disease and that increased plasma FGF23
      concentration is a cardiovascular risk factor in these patients. The aim of this
      prospective, single-arm, open-label clinical study was to assess the influence of
      6-month cinacalcet treatment on plasma FGF23 concentration in haemodialysed
      patients with secondary hyperparathyroidism (sHPT). DESIGN, PATIENTS AND
      MEASUREMENTS: In 58 haemodialysed patients with sHPT (parathormone PTH > 300
      ng/l), serum PTH, FGF23, calcium and phosphate concentrations were assessed
      before the first dose of cinacalcet and after 3 and 6 months of treatment.
      RESULTS: Serum PTH concentration decreased significantly after 3 and 6 months of
      treatment, and the mean serum calcium and phosphate concentrations remained
      stable during the treatment period. Plasma FGF23 concentration (geometric mean
      with 95% confidence index) decreased after 3 and 6 months of treatment from 354
      (261-481) ng/l to 295 (204-428) ng/l; P = 0.099 and to 183 (117-285) ng/l; P =
      0.015, respectively. FGF23 concentration decreased in 52% of patients. In
      multivariate regression analysis, plasma FGF23 concentration changes were
      explained by the changes in serum phosphate, but not by serum PTH or calcium
      changes or by the dose of cinacalcet. CONCLUSIONS: 1. Cinacalcet treatment
      decreases plasma FGF23 concentration in haemodialysed patients with secondary
      hyperparathyroidism. 2. The decrease in plasma FGF23 concentration seems to be
      related to the decrease in serum phosphate concentration.

PMID- 24111497
TI  - Amelioration of Muc5b mucin hypersecretion is enhanced by IL-33 after 2-APB
      administration in a murine model of allergic rhinitis.
AB  - We attempted to clarify whether hypersecretion of Muc5b mucin from mouse nasal
      submucosal glands that is enhanced by interleukin (IL)-33 under allergic
      conditions can be ameliorated by administration of 2-APB. Immunohistochemistry
      was used to examine both the distribution of T cells in the nasal mucosa of an
      allergic rhinitis mouse model and expressions of IL-33 receptor ST2 and Muc5b
      protein in mouse submucosal gland cells. The amounts of protein and mRNA of
      Orai1, Muc5b, IL-4, IL-5, IL-13 and IL-33 in mouse nasal lavage fluid (NLF) and
      nasal mucosa were determined using enzyme-linked immunosorbent assay and real
      time reverse transcription-polymerase chain reaction. Expressions of Orai1,
      Muc5b, IL-4, IL-5, IL-13 and IL-33 were up-regulated in the allergic state and IL
      33 increased the levels of Muc5b, IL-4, IL-5 and IL-13, but did not influence
      proliferation of T cells; however, ST2 was diminished in nasal submucosal gland
      cells. 2-APB reduced proliferation of T cells and the Orai1 level in the nasal
      mucosa. It also reduced the concentrations of IL-4, IL-5 and IL-13 in NLF and
      nasal mucosa, and hypersecretion of Muc5b from glandular cells that was enhanced
      by IL-33, but did not affect IL-33 production. 2-APB decreased Muc5b mucin
      hypersecretion from submucosal gland that was enhanced by IL-33 in allergic mice
      by limiting Ca(2+) release-activated Ca(2+) channel activity in which Orai1 plays
      a crucial role in the gland cells and/or by controlling channel activation in T
      cells and proliferation of these cells.

PMID- 24111498
TI  - Thiosemicarbazide-ferricyanide reduction for the histochemical demonstration of
      aldehydes in tissue sections.
AB  - Aldehydes produced from carbohydrates by oxidation or acid hydrolysis may be
      visualized by application of aqueous thiosemicarbazide followed by Schmorl's
      ferricyanide reduction. The thiosemicarbazide reacts with the aldehydes by its
      hydrazine group, while its thiocarbamyl group remains active. The thiocarbamyl
      moiety is a strong reducing group that converts ferricyanide to ferrocyanide in
      Schmorl's reaction. The ferrocyanide is trapped immediately by the ferric salt,
      which deposits Prussian blue at the site of the aldehydes thereby demonstrating
      the location of the original substance.

PMID- 24111499
TI  - Listeria infection inhibits IgE production in regional lymph nodes by suppressing
      chemotaxis of basophils to lymph nodes.
AB  - Infection with Listeria induces a dominant shift to the Th1 immune response and
      inhibits the Th2 response. Papain is frequently utilized in animal models of
      allergies. Papain administration induces chemotaxis of basophils to regional
      lymph nodes (LNs) and production of interleukin (IL)-4 by basophils, resulting in
      a Th2-dominant status and increased IgE production in LNs. In this model,
      production of immunoglobulin (Ig) E by LN cells is primarily controlled by IL-4
      produced by basophils. Based on this model, it was postulated that Listeria
      monocytogenes (Lm) infection suppresses IgE production by LN cells. Therefore,
      the effects of Lm infection on a papain-induced mouse model of allergies were
      investigated. Following s.c. injection of papain, basophils transiently migrated
      to draining LNs because of the effects of chemokine (C-C) motif ligand (CCL) 24
      and secreted IL-4, inducing a Th2 response. Lm infection blocked recruitment of
      basophils into the popliteal LNs by inhibiting CCL24 production. Papain-induced
      class switch recombination (CSR) to IgE is inhibited by Lm infection, whereas CSR
      to IgG1 is not affected by the same treatment. Therefore, the CSR of IgG1 to IgE
      is basophil-dependent, whereas the CSR of IgM to IgG1 is basophil-independent.
      Hence, Lm infection suppresses CSR to IgE without affecting CSR to IgG1. 

PMID- 24111500
TI  - Body temperature and major neurological improvement in tPA-treated stroke
      patients.
AB  - BACKGROUND: Major neurological improvement (MNI) at 24 hours represents a marker
      of early recanalization in ischaemic stroke. Although low body temperature is
      considered neuroprotective in cerebral ischaemia, some studies have suggested
      that higher body temperature may promote clot lysis in the acute phase of
      ischaemic stroke. We hypothesized that higher body temperature was associated
      with MNI in severe stroke patients treated with tPA, suggesting a beneficial
      effect of higher body temperature on clot lysis and recanalization. METHODS:
      Patients with ischaemic stroke or transient ischaemic attack (TIA) treated with
      tPA between February 2006 and August 2012 were prospectively included and
      retrospectively analysed. Body temperature was measured upon admission. MNI was
      defined by a >=8 point improvement in NIHSS score at 24 hours as compared to
      NIHSS score on admission. No significant improvement (no-MNI) was defined by
      either an increase in NIHSS score or a decrease of <=2 points at 24 hours in
      patients with an admission NIHSS score of >=8. RESULTS: Of the 2351 patients
      admitted with ischaemic stroke or TIA, 347 patients (14.8%) were treated with
      tPA. A total of 32 patients (9.2%) had MNI and 56 patients (16.1%) had no-MNI.
      Patients with MNI had higher body temperatures compared with patients with no-MNI
      (36.7 degrees C vs 36.3 degrees C, P = 0.004). Higher body temperature was
      independently associated with MNI when adjusted for confounders (OR 5.16, P =
      0.003). CONCLUSION: Higher body temperature was independently associated with MNI
      in severe ischaemic stroke patients treated with tPA. This may suggest a
      beneficial effect of higher body temperature on clot lysis and recanalization.

PMID- 24111501
TI  - Effect of solvents and methods of stirring in extraction of lycopene, oleoresin
      and fatty acids from over-ripe tomato.
AB  - Lycopene and oleoresin extraction from powder of tomato over-ripe by three
      agitation methods and four solvents have been evaluated. Also, tomato powder and
      the oleoresins were characterized biochemically. On average, the moisture content
      of powder was found to be 4.30, ash 8.90, proteins 11.23 and lipids 4.35 g 100 g(
      1). The best oleoresin extraction yield was achieved by combining sonication and
      acetone at 1.43 g 100 g(-1). The greatest amount of lycopene (65.57 +/- 0.33 mg
      100 g(-1)) was also obtained using the same treatment. The presence of trans
      lycopene was positively confirmed by HPLC and FTIR. In oleoresins, linoleic acid
      (C18:2n6) was the predominant with 50% of total fatty acids, whereas stearic acid
      (C18:0) is presented in a smaller proportion (5%). A simple and suitable method
      for extraction of lycopene from over-ripe tomato was optimized. In industrial
      applications, tomato by-products are a viable source of analytes, such as
      lycopene and unsaturated fatty acids.

PMID- 24111502
TI  - Randomized controlled trial of fish oil supplementation in pregnancy on childhood
      allergies.
AB  - BACKGROUND: Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may
      modulate the development of IgE-mediated allergic disease and have been proposed
      as a possible allergy prevention strategy. The aim of this study was to determine
      whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated
      allergic disease in their children. METHODS: Follow-up of children (n = 706) at
      hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise
      Mother Infant Outcome randomized controlled trial. The intervention group (n =
      368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3
      LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338)
      received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of
      allergic disease was made during medical assessments at 1 and 3 years of age.
      RESULTS: No differences were seen in the overall percentage of children with IgE
      mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and
      control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78;
      95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8%
      of children in the n-3 LCPUFA group had eczema with sensitization compared with
      19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P =
      0.10). CONCLUSIONS: Overall, n-3 LCPUFA supplementation during pregnancy did not
      significantly reduce IgE-associated allergic disease in the first 3 years of
      life. Further studies should examine whether the nonsignificant reductions in IgE
      associated allergies are of clinical and public health significance.

PMID- 24111503
TI  - Impact of a phytoplankton bloom on the diversity of the active bacterial
      community in the southern North Sea as revealed by metatranscriptomic approaches.
AB  - Despite their importance for ecosystem functioning, little is known about the
      composition of active marine bacterioplankton communities. Hence, this study was
      focused on assessing the diversity of these communities in the southern North Sea
      and examining the impact of a phytoplankton spring bloom on the ambient
      bacterioplankton community. Community composition in and outside the bloom was
      assessed in 14 samples by pyrosequencing-based analysis of 16S rRNA gene
      amplicons generated from environmental RNA. The data set comprised of 211 769 16S
      rRNA gene sequences. Proteobacteria were the predominant phylogenetic group with
      Alphaproteobacteria and Gammaproteobacteria as the most abundant classes.
      Actinobacteria and Bacteroidetes were identified in minor abundances. Active
      bacterial communities were dominated by few lineages such as the Roseobacter RCA
      cluster and the SAR92 clade. Community structures of three selected samples were
      also assessed by direct sequencing of cDNA generated from rRNA-depleted
      environmental RNA. Generated data sets comprised of 988 202 sequences. Taxonomic
      assignment of the reads confirmed the predominance of Proteobacteria. The
      examined phytoplankton spring bloom affected the bacterioplankton community
      structures significantly. Bacterial richness was reduced in the bloom area, and
      the abundance of certain bacterial groups was affected by bloom presence. The
      SAR92 clade and the Roseobacter RCA cluster were significantly more abundant and
      active in the bloom. Functions affected by the bloom include photosynthesis,
      protein metabolism, and DNA metabolism. 

PMID- 24111504
TI  - A belief in the soul may contribute to the stress experienced in the dissecting
      room.
AB  - The aim of this research was to explore whether medical students believe in a
      soul and how this may affect their dissecting experience. Three questionnaires
      were delivered electronically to the 2011 cohort of second-year medical students
      over a 2-year period. At the University of Otago, students enter medicine via
      three categories: Health Sciences First Year (following 1 year of university);
      postgraduate (following a Bachelors or higher degree); and 'other' category entry
      (Allied Health Professional or 3 years after a Bachelors degree). The entry
      category, age, ethnicity and gender of the students were collected; 51.6% of the
      students believed in the concept of a soul. On a scale of 1-5, students ranked
      the importance of religion/spirituality as 2.69. Those who believed in a soul
      were more likely to have a religious/spiritual component to their life and be
      males or 'other' category entrants. However, there were many students who
      believed in the soul who did not have a religious/spiritual association,
      suggesting that this belief extends beyond religion. Those who believed in a soul
      had significantly higher anticipatory stress and experienced higher levels of
      stress during dissection. A higher proportion of students in the 'other' category
      entrants believed in the concept of the soul and also had significantly higher
      levels of stress during dissection. Our data suggest that a belief in a soul may
      affect students' experiences in dissecting. Incorporating the teaching of
      humanities with anatomy may help medical students as they assimilate both the
      biomedical and philosophical aspects of dissection.

PMID- 24111505
TI  - Critical role of peripheral drug actions in experience-dependent changes in
      nucleus accumbens glutamate release induced by intravenous cocaine.
AB  - Recent studies reveal that cocaine experience results in persistent neuroadaptive
      changes within glutamate (Glu) synapses in brain areas associated with drug
      reward. However, it remains unclear whether cocaine affects Glu release in drug
      naive animals and how it is altered by drug experience. Using high-speed
      amperometry with enzyme-based and enzyme-free biosensors in freely moving rats,
      we show that an initial intravenous cocaine injection at a low self-administering
      dose (1 mg/kg) induces rapid, small and transient Glu release in the nucleus
      accumbens shell (NAc), which with subsequent injections rapidly becomes a much
      stronger, two-component increase. Using cocaine-methiodide, cocaine's analog that
      does not cross the blood-brain barrier, we confirm that the initial cocaine
      induced Glu release in the NAc has a peripheral neural origin. Unlike cocaine,
      Glu responses induced by cocaine-methiodide rapidly habituate following repeated
      exposure. However, after cocaine experience this drug induces cocaine-like Glu
      responses. Hence, the interoceptive actions of cocaine, which essentially precede
      its direct actions in the brain, play a critical role in experience-dependent
      alterations in Glu release, cocaine-induced neural sensitization and may
      contribute to cocaine addiction. Using high-speed amperometry with enzyme-based
      biosensors in freely moving rats, we show that initial intravenous cocaine
      induces rapid, transient glutamate (Glu) release in the Nac (Nucleus accumbens),
      rapidly becoming a stronger, two-component increase with subsequent injections.
      We show that the peripheral actions of cocaine, which precedes its direct central
      actions, play a critical role in experience-dependent alterations in Glu release,
      possibly contributing to cocaine addiction.

PMID- 24111506
TI  - A comparison of Child Health Programmes recommended for preschool children in
      selected high-income countries.
AB  - BACKGROUND: The UK Child Health Programme (CHP) aims to ensure that children
      attain their development and health potential. It comprises a series of proactive
      child health reviews incorporating growth and development surveillance and health
      promotion; routine immunizations; and certain screening tests, and is offered to
      all children. The evidence underpinning different elements of the CHP varies from
      robust to sparse, and consequently there is uncertainty about optimal programme
      design. This study aimed to compare the CHP currently recommended in the UK with
      that recommended in selected other high-income countries in order to inform
      ongoing CHP policy development. METHODS: The CHP recommended for preschool
      children in the UK was compared with that in Australia; Canada; the USA; and
      Sweden using a combination of literature review, focused website searches, and
      consultation with experts in the countries studied. Delivery, content, and uptake
      of child health reviews, immunizations, and screening were considered. RESULTS:
      All the countries studied recommend CHP services including child health reviews,
      immunizations, and screening to their preschool populations. Despite this
      superficial uniformity, considerable variation exists between countries in the
      detail of CHP delivery and content. The UK programme is relatively narrow in
      scope, offering the fewest child health reviews, a relatively restricted
      immunization programme (although some expansion is planned), and limited newborn
      bloodspot screening. Internationally comparable data on the uptake/coverage of
      CHP services are patchy: the available information suggests substantial variation
      between and within countries in the uptake of child health reviews. CONCLUSIONS:
      In the absence of uncontested evidence on the 'ideal' CHP for preschool children,
      demonstrating variation between countries in recommended programmes provides
      valuable contextual information for policy makers. Further work looking at
      relationships between CHP services and children's outcomes would add further
      value.

PMID- 24111507
TI  - Blockade of tumour necrosis factor-alpha in experimental autoimmune
      encephalomyelitis reveals differential effects on the antigen-specific immune
      response and central nervous system histopathology.
AB  - In various autoimmune diseases, anti-tumour necrosis factor (TNF)-alpha treatment
      has been shown to reduce both clinical disease severity and T helper type 1
      (Th1)1/Th17 responses. In experimental autoimmune encephalomyelitis (EAE),
      however, the role of TNF-alpha has remained unclear. Here, C57BL/6 mice were
      immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and
      treated with anti-TNF-alpha, control antibody or vehicle. The clinical disease
      course, incidence and severity were assessed. On day 20 after immunization the
      antigen-specific Th1/Th17 response was evaluated by enzyme-linked immunospot
      (ELISPOT) in spleen and central nervous system (CNS). Also, the extent of spinal
      cord histopathology was analysed on semi- and ultrathin sections. Our results
      demonstrate that anti-TNF-alpha treatment reduced the incidence and delayed the
      onset of EAE, but had no effect on disease severity once EAE had been
      established. Whereas anti-TNF-alpha treatment induced an increase in splenic
      Th1/Th17 responses, there was no effect on the number of antigen-specific
      Th1/Th17 cells in the spinal cord. Accordingly, the degree of CNS histopathology
      was comparable in control and anti-TNF-alpha-treated mice. In conclusion, while
      the anti-TNF-alpha treatment had neither immunosuppressive effects on the
      Th1/Th17 response in the CNS nor histoprotective properties in EAE, it enhanced
      the myelin-specific T cell response in the immune periphery.

PMID- 24111508
TI  - Knowledge is power? The role of experiential knowledge in genetically 'risky'
      reproductive decisions.
AB  - Knowledge of the condition being tested for is increasingly acknowledged as an
      important factor in prenatal testing and screening decisions. An analysis of the
      way in which family members living with an inheritable condition use and value
      this knowledge has much to add to debates about whether and how this type of
      knowledge could be made available to prospective parents facing screening
      decisions. This article reports on in-depth interviews (conducted between 2007
      and 2009) with 61 people with a genetic condition, spinal muscular atrophy (SMA)
      in their family. Many participants reported that their intimate familial
      knowledge of SMA offered them valuable insights with which they could imagine
      future lives. Other participants, however, found themselves trapped between their
      experiential knowledge of SMA and their (often) competing responsibility to
      maintain the wellbeing of their family. Still, others established a hierarchy of
      knowledge to rank the authenticity of different family member's accounts of SMA
      in order to discredit or justify their decisions. This article highlights the way
      in which experiential knowledge of the condition being tested for cannot be
      unproblematically assumed to be a useful resource in the context of prenatal
      testing decisions and may actually constrain reproductive decisions. 

PMID- 24111510
TI  - Cell culture condition-dependent impact of AGE-rich food extracts on kinase
      activation and cell survival on human fibroblasts.
AB  - Advanced glycation end products (AGEs) are stable end products of the Maillard
      reaction. Effects of food extracts are often initially analysed in cellular test
      systems and it is not clear how different cell culture conditions might influence
      the results. Therefore, we compared the effects of two models for AGE-rich food,
      bread crust and coffee extract (CE) on WI-38 human lung fibroblasts under
      different cell culture conditions (sub-confluent versus confluent cells, with and
      without serum). WI-38 cells responded to coffee and bread crust extract (BCE)
      with a rapid phosphorylation of PKB (AKT), p42/44 MAPK (ERK 1/2) and p38 MAPK,
      strongly depending on culture conditions. BCE resulted in increased cell numbers,
      whereas CE appeared to be cytotoxic. When cell numbers under all culture
      conditions and treatments were correlated with kinase phosphorylation, the
      relation between phospho-p38 MAPK and phospho-AKT represented a good, cell
      culture condition-independent predictor of cell survival.

PMID- 24111509
TI  - Non-compliance and inertia in hypertensive Spaniards at high cardiovascular risk:
      CUMPLE study.
AB  - OBJECTIVE: To assess non-compliance (NC) and therapeutic inertia (TI) after 6
      months of follow-up in hypertensive patients with poorly controlled blood
      pressure and high cardiovascular risk. RESEARCH DESIGN AND METHODS: Longitudinal,
      multicentre study; 3900 uncontrolled hypertensive patients were recruited from
      585 primary healthcare centres. Tablets were counted during visits at baseline,
      1, 3 and 6 months. A tablet count between 80-100% was considered as compliant.
      Multivariate logistic regression was performed to determine variables associated
      with NC and TI. RESULTS: A total of 3636 patients completed, mean age was 64.8
      (SD 10.8) years, 53.7% being male. After one month, 61.8% (60.2-63.4) had
      uncontrolled blood pressure, 39.5% (37.9-41.1) were NC and 52.3% (50.2-54.4) had
      TI. At the end of follow-up, uncontrolled blood pressure was 34.6% (33.1-36.1) (p
      < 0.05), NC was 46.8% (45.2-48.4) (p < 0.05) and TI was 34.2% (31.6-36.8) (p <
      0.05). The variable associated with NC was greatest number of antihypertensive
      treatments (OR 1.09, 95% CI 1.05-1.13, p < 0.001), and variables associated with
      TI were least number of antihypertensive drugs (OR 0.88, 95% CI 0.84-0.98, p <
      0.001) and least number of diseases suffered (OR 0.95, 95% CI 0.92-0.98, p =
      0.002). LIMITATIONS: Due to the complexity of measuring compliance, we have to
      assume measurement bias. CONCLUSIONS: Among uncontrolled hypertensive patients,
      after completing 6 months follow-up, approximately one out of two patients were
      NC and one out of three physicians committed TI.

PMID- 24111511
TI  - Translating and testing breast cancer risk reduction messages for mothers of
      adolescent girls.
AB  - Emerging scientific findings regarding breast cancer science are typically
      presented only in discipline specific journals in which the general public and
      those at risk have limited access, creating a development-to-delivery gap between
      the state of the science and public knowledge. A lack of collaboration between
      scientists, communication experts, and community partners further compounds this
      lack of information available to the public. The present study translates recent
      scientific findings about environmental breast cancer risks into palatable
      magazine-style messages for mothers of young daughters as a strategy to meet the
      call for greater translation and dissemination of scientific results to the lay
      public. Results from focus groups indicate that mothers actually want more
      science in messages and greater explication of findings that indicate causality.
      Mothers also expect polished, professional messages that are representative of
      their daughters and provide a source for further information seeking purposes.
      Recommendations for future translation and message design endeavors are
      discussed. 

PMID- 24111512
TI  - Ability to manage everyday technology after acquired brain injury.
AB  - PURPOSE: To investigate and describe how persons with an acquired brain injury
      (ABI) manage everyday technology (ET) in their daily activities and to explore
      whether the ability to manage ET was related to the severity of the disability.
      METHOD: Eighty-one persons with ABI were observed while managing ET by using the
      Management of Everyday Technology Assessment (META). The Glasgow Outcome Scale
      Extended (GOSE) was used to assess the severity of disability after the ABI. A
      computer application of a Rasch measurement model was used to generate measures
      of the participants' ability to manage ET and the measures were compared
      groupwise with analysis of covariance (ANCOVA). RESULTS: The degree of severity
      of disability had a significant main effect on the ability to manage ET. The
      groups with severe and moderate disability exhibited a significantly lower
      ability to manage ET compared to the group with good recovery. CONCLUSION: The
      result indicates that the ability to manage ET in daily activities can be related
      to the global severity of disability after ABI. This demonstrates the importance
      of considering the ability to manage ET to support the performance of activities
      at home, at work and in society in persons with ABI.

PMID- 24111513
TI  - Staphylococcal vaccine development: review of past failures and plea for a future
      evaluation of vaccine efficacy not only on staphylococcal infections but also on
      mucosal carriage.
AB  - Staphylococcal disease represents a universal burden including acute, life
      threatening infections as well as chronic infections usually associated with
      foreign materials. Infections occur notably in permanent carriers of
      Staphylococcus aureus. To date, all the attempts to develop an efficacious
      vaccine against S. aureus have failed. Failures in vaccine clinical trials might
      be related to a focus on single targets and development of humoral-based vaccines
      rather than vaccines with a combination of antigens stimulating both humoral and
      cellular immunity. The end points of these unsuccessful trials were a reduction
      in mortality or bacteremia, whereas the patient's decolonization was not
      assessed. Adopting the latter point of view, the aim of this article is to
      discuss nasal mucosal decolonization as a complementary marker of vaccine
      efficacy for clinical research in vaccine development. 

PMID- 24111514
TI  - Multi-level modelling of longitudinal child growth data from the Birth-to-Twenty
      Cohort: a comparison of growth models.
AB  - BACKGROUND: Different structural and non-structural models have been used to
      describe human growth patterns. However, few studies have compared the fitness of
      these models in an African transitioning population. AIM: To find model(s) that
      best describe the growth pattern from birth to early childhood using mixed effect
      modelling. SUBJECTS AND METHODS: The study compared the fitness of four
      structural (Berkey-Reed, Count, Jenss-Bayley and the adapted Jenss-Bayley) and
      two non-structural (2nd and 3rd order Polynomial) models. The models were fitted
      to physical growth data from an urban African setting from birth to 10 years
      using a multi-level modelling technique. The goodness-of-fit of the models was
      examined using median and maximum absolute residuals, Akaike Information
      Criterion (AIC) and Bayesian Information Criterion (BIC). RESULTS: There were
      variations in how the different models fitted to the data at different
      measurement occasions. The Jenss-Bayley and the polynomial models did not fit
      well to growth measurements in the early years, with very high or very low
      percentage of positive residuals. The Berkey-Reed model fitted consistently well
      over the study period. CONCLUSION: The Berkey-Reed model, previously used and
      fitted well to infancy growth data, has been shown to also fit well beyond
      infancy into childhood.

PMID- 24111515
TI  - Effect of pursed-lip breathing in patients with COPD: Linear and nonlinear
      analysis of cardiac autonomic modulation.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effect of pursed-lip
      breathing (PLB) on cardiac autonomic modulation in individuals with chronic
      obstructive pulmonary disease (COPD) while at rest. METHODS: Thirty-two
      individuals were allocated to one of two groups: COPD (n = 17; 67.29 +/- 6.87
      years of age) and control (n = 15; 63.2 +/- 7.96 years of age). The groups were
      submitted to a two-stage experimental protocol. The first stage consisted of the
      characterization of the sample and spirometry. The second stage comprised the
      analysis of cardiac autonomic modulation through the recording of R-R intervals.
      This analysis was performed using both nonlinear and linear heart rate
      variability (HRV). In the statistical analysis, the level of significance was set
      to 5% (p <= 0.05). RESULTS: PLB promoted significant increases in the SD1, SD2,
      RMSSD and LF (ms(2)) indices as well as an increase in alpha1 and a reduction in
      alpha2 in the COPD group. A greater dispersion of points on the Poincare plots
      was also observed. The magnitude of the changes produced by PLB differed between
      groups. CONCLUSION: PLB led to a loss of fractal correlation properties of heart
      rate in the direction of linearity in patients with COPD as well as an increase
      in vagal activity and impact on the spectral analysis. The difference in the
      magnitude of the changes produced by PLB between groups may be related to the
      presence of the disease and alterations in the respiration rate.

PMID- 24111516
TI  - Epoxy-based hydrogels investigated by high-frequency dielectric relaxation
      spectroscopy.
AB  - Using high-frequency dielectric relaxation spectroscopy, nanophase-separated
      structures of epoxy-based hydrogels were investigated as a function of water
      content at 25  degrees C. The dielectric spectra resulting from the hydrogels
      were reasonably decomposed into two Debye-type and two Cole-Cole-type relaxation
      modes. The fastest Debye-type mode, found at 8.3 ps, was attributed to the
      rotational relaxation process of free water molecules in the bulk state. The
      other Debye-type mode, at ca. 20-34 ps, originates from the exchange process of
      water molecules that are hydrogen-bonded to the hydrophilic epoxy network
      portions for free bulk ones. The first Cole-Cole-type mode observed, at ca. 20
      370 ps, was assigned to the complicated dynamics for electric dipole moments of
      the hydrophilic groups in the epoxy networks (mainly monomeric oxyethylene
      units). The slowest major Cole-Cole-type mode, at 5-29 ns, was attributed to the
      Maxwell-Wagner-Sillars polarization process and confirmed the presence of the
      nanophase-separated structures as revealed by the previous small-angle neutron
      scattering experiments. 

PMID- 24111517
TI  - Tetranuclear lanthanide (III) complexes containing dimeric subunits: single
      molecule magnet behavior for the Dy4 analogue.
AB  - The reaction of the lanthanide(III) salts [Dy(III), Tb(III), and Gd (III)] with a
      hetero donor chelating ligand N'-(2-hydroxy-3-methoxybenzylidene)-6
      (hydroxymethyl) picolinohydrazide (LH3) and pivalic acid (PivH) in the presence
      of tetra-n-butylammonium hydroxide (TBAH) afforded the tetranuclear Ln(III)
      coordination compounds, [Ln4(LH)2(LH2)2(MU2-eta(1)eta(1)Piv)2(eta(1)Piv)4].2CHCl3
      [Ln = Dy(1), Tb(2), and Gd(3)]. The molecular structure of these complexes
      reveals that the tetranuclear derivatives are composed of two dinuclear subunits
      which are interconnected through the coordination action of the picolinoyl
      hydrazine ligand. Within each subunit two different types of Ln(III) ions are
      present. One of these is eight-coordinate in a distorted triangular dodecahedral
      geometry while the other is nine-coordinate in a distorted spherical capped
      square antiprism geometry. Alternating current (ac) susceptibility measurements
      of complex 1 reveal a frequency- and temperature-dependent two step out-of-phase
      signals under 1kOe DC field which is characteristic of a single-molecule magnet
      (SMM) behavior. Analysis of the magnetic data afforded the anisotropic barriers
      and relaxation times: Delta/kB = 62.6 K, tau0 = 8.7 * 10(-7) s; Delta/kB = 26.3
      K, tau0 = 1.26 * 10(-6) s for the slow and fast relaxations respectively. 

PMID- 24111518
TI  - Halogen and chalcogen cation pools stabilized by DMSO. Versatile reagents for
      alkene difunctionalization.
AB  - Halogen and chalcogen cations (X(+) = Br(+), I(+), ArS(+), and ArSe(+)) were
      generated by low-temperature electrochemical oxidation in the presence of
      dimethyl sulfoxide (DMSO) and were accumulated in the solution. DFT calculations
      indicated that DMSO stabilizes these cations by coordination. The complexes of
      I(+) with one and two DMSO molecules were observed by cold-spray-ionization MS
      analyses. The stability of the resulting cation pools of X(+) increased in the
      order of Br(+) < I(+) < ArS(+) < ArSe(+), which could be explained in terms of
      the electronegativity of X. The cation pools served as versatile reagents for
      organic synthesis; the reactions with alkenes gave beta-X-substituted
      alkoxysulfonium ions, which were converted to the corresponding carbonyl
      compounds by the treatment with triethylamine, whereas the treatment with
      methanol gave the corresponding alcohols. The reactions with aminoalkenes and 1,6
      dienes gave the cyclized products. 

PMID- 24111519
TI  - Prevention of falls to a lower level: evaluation of an occupational health and
      safety intervention via subsidies for the replacement of scaffolding.
AB  - The objective of this study is to evaluate the impact of a subsidy policy for
      construction companies in Andalusia (Spain), which enables them to acquire new
      scaffolds. The rate of falls from scaffolds within the Andalusian construction
      sector in the period 2009-2011 was analysed. A randomised controlled trial was
      not possible as the subsidy was granted according to a public and competitive
      call. A quasi-experimental design based on an intervention group (subsidised
      companies) and a control group was chosen. Companies in the control group were
      selected from the social security census of companies in order to avoid selection
      bias. The subsidy policy has led to an overall 71% decrease in the rate of
      accident involving falls to a lower level in the companies that received grants
      in the period 2009-2011. The confidence interval for the comparison for the
      before-after difference in rates between the intervention group and the control
      group is found significant (confidence 95%, p = 0.05). The improvement of
      scaffolds was effective in reducing rates of accident with falls to a lower
      level. This intervention should be a priority in public policies. The process of
      standardisation of equipment with high accident risk should be developed further.

PMID- 24111520
TI  - Surface area measurement of graphene oxide in aqueous solutions.
AB  - Graphene oxide (GO) forms persistent dispersions in aqueous solutions up to
      concentrations of 0.2 mg mL(-1). Addition of methylene blue (MB) to these aqueous
      dispersion of GO gives rise to the observation in optical spectroscopy of new
      absorption bands that are indicative of the formation of MB/GO conjugates. Four
      new absorption maxima have been characterized, and their intensity varies
      depending on the relative concentration of MB with respect to GO. Two of these
      bands appearing at 677 and 757 nm correspond to individual MB molecules adsorbed
      on neutral or acid sites of GO, respectively. Two other bands at 615 and 580 nm
      are attributable to adsorbed MB molecules showing interaction with other neighbor
      dye molecules at incomplete (615 nm) or complete (580 nm) surface coverage.
      Complete coverage of GO surface by MB causes the formation of a precipitate and
      the separation of the MB/GO conjugate. EDS mapping of carbon and sulfur atoms of
      MB/GO conjugate indicates the homogeneous distribution of MB molecules coating GO
      sheets. A simple and reliable protocol for surface area measurement and
      determination of the level of aggregation for GO dispersions in water has been
      proposed by determining the amount of MB that leads to the maximum intensity of
      the 580 nm band and precipitation of the MB/GO conjugate. Specific surface area
      as high as 736.6 m(2) g(-1) in the range of the theoretical value for GO has been
      experimentally measured for diluted GO solutions, but aggregation levels of 15%
      were estimated for GO concentration of 50 MUg mL(-1). 

PMID- 24111521
TI  - ROCK inhibition enhances aggrecan deposition and suppresses matrix
      metalloproteinase-3 production in human articular chondrocytes.
AB  - Homeostasis of articular cartilage is maintained by a balance between catabolism
      and anabolism. Matrix metalloproteinase-3 (MMP-3) catabolism of cartilaginous
      extracellular matrix (ECM), including aggrecan (AGN), is an important factor in
      osteoarthritis progression. We previously reported that inhibition of Rho
      associated coiled-coil forming kinase (ROCK), an effector of Rho family GTPases,
      activates the chondrogenic transcription factor SRY-type high-mobility-group box
      (SOX) 9 and prevents dedifferentiation of monolayer-cultured chondrocytes. We
      hypothesized that ROCK inhibition prevents chondrocyte dedifferentiation by
      altering the transcriptional balance between MMP-3 and AGN. Normal human
      articular chondrocytes were cultured in the presence or absence of ROCK inhibitor
      (ROCKi, Y-27632). Expression of MMP-3 and AGN during monolayer cultivation was
      assessed by quantitative real-time PCR and western blot analysis. Chondrogenic
      redifferentiation potential of ROCKi-treated chondrocytes was evaluated by
      immunohistological analysis of pellet cultures. ROCKi treatment suppressed MMP-3
      expression in monolayer- and pellet-cultured chondrocytes but increased AGN
      expression. Chromatin immunoprecipitation revealed that the association between
      transcription factors E26 transformation specific (ETS)-1 and SOX9 and their
      target genes MMP-3 and AGN, respectively, was affected by ROCKi treatment. ROCKi
      decreased the association between ETS-1 and its binding sites on the MMP-3
      promoter, whereas ROCKi promoted the interaction between SOX9 and the AGN
      promoter. Our results suggest that ROCK inhibition may have an important role in
      modulating the balance between degradation and synthesis of cartilaginous ECM, a
      finding that may facilitate development of techniques to prepare differentiated
      chondrocytes for cartilage regeneration therapy.

PMID- 24111522
TI  - The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast
      differentiation.
AB  - The aim of this study was to determine the role of the mitogen-activated protein
      kinase kinase (MEK) 5/extracellular signal-regulated kinase (ERK) 5 pathway in
      osteoblast differentiation promoted by intermittent fluid shear stress (FSS).
      MC3T3-E1 osteoblastic cells were subjected to 12 dyn/cm(2) intermittent FSS, and
      the phenotypic markers for osteoblast differentiation, such as alkaline
      phosphatase (ALP) activity and expression of osteopontin (OPN) and osteocalcin
      (OCN), were then examined. The results showed that intermittent FSS could
      stimulate ERK5 phosphorylation, ALP activity and the expression of OPN and OCN.
      When the MEK5/ERK5 pathway was selectively inhibited by BIX02189, ALP activity
      was suppressed, and the expression of OPN and OCN was downregulated. Intermittent
      FSS induce the expression of Runt-related transcription factor-2 (Runx-2), which
      is involved in osteoblast differentiation by promoting the transcription of the
      above genes. Furthermore, the expression of Runx-2 was also reduced after
      treatment with BIX02189. Finally, we found that intermittent FSS was a more
      intense stimulus than steady FSS for promoting osteoblast differentiation. In
      summary, our results suggest that the MEK5/ERK5 pathway mediates osteoblast
      differentiation promoted by intermittent FSS, which was more effective than
      steady FSS in the differentiation process. The MEK5/ERK5 pathway also mediates
      FSS-induced Runx-2 expression in osteoblast differentiation.

PMID- 24111523
TI  - Work-family conflict, health services and medication use among dual-income
      couples in Europe.
AB  - Combination pressure or work-life imbalance is linked to adverse health. However,
      it remains unclear how work-family conflict is related to healthcare utilisation.
      Does work-family conflict function as a barrier or as a facilitator in relation
      to the use of health services and prescription medication? Lack of time may
      prevent people from visiting a doctor when they feel unwell. However, combination
      pressure can also be expected to intensify the use of health services, as the
      need for a quick fix is prioritised. Further, do women and men differ in their
      susceptibility to medicalisation and time pressure resulting from work-life
      imbalance? This article investigates the use of health services and prescription
      medication of dual-income couples with children, based on data from 23 countries
      in the European Social Survey round 2 (N(women) = 3755; N(men) = 3142). It was
      found that medical services and prescription medications are used more frequently
      in dual-income couples experiencing work-to-family spillover, but for women only
      this is irrespective of their self-reported health. Family-to-work spillover does
      not result in increased health service or medication use for either men or women.
      While women opt for a medical response to work-life imbalance, men's reluctance
      to seek formal health support is confirmed.

PMID- 24111525
TI  - Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking alpha
      lipoic acid.
AB  - OBJECTIVE: Lipoic acid (LA) is a widely used nutritional supplement and is
      sometimes used as an adjuvant treatment for diabetic neuropathy and other
      conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of
      spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of
      autoantibodies against endogenous insulin despite no prior exposure to exogenous
      insulin. In Japanese individuals, IAS is associated with the human leucocyte
      antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl
      containing compounds including LA. Only one case has been reported in Caucasians.
      We now report six Caucasian patients taking LA with IAS and describe a unique HLA
      subtype in these patients. RESEARCH DESIGN AND METHODS: Six Caucasian patients (M
      = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting
      and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms.
      No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms
      appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case
      histories and standard laboratory analyses were utilized. RESULTS:
      Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All
      patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day).
      HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA
      DRB1*04:06 allele was present in one patient. CONCLUSIONS: This is the first
      report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele,
      implicating this allele in the genetic susceptibility to IAS in Caucasians. The
      greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other
      populations, combined with the growing use of LA in developed countries, may be a
      future predictor of additional cases of IAS.

PMID- 24111524
TI  - Celastrol prevents cadmium-induced neuronal cell death via targeting JNK and PTEN
      Akt/mTOR network.
AB  - Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative
      diseases. Celastrol, a plant-derived triterpene, has shown neuroprotective
      effects in various disease models. However, little is known regarding the effect
      of celastrol on Cd-induced neurotoxicity. Here, we show that celastrol protected
      against Cd-induced apoptotic cell death in neuronal cells. This is supported by
      the findings that celastrol strikingly attenuated Cd-induced viability reduction,
      morphological change, nuclear fragmentation, and condensation, as well as
      activation of caspase-3 in neuronal cells. Concurrently, celastrol remarkably
      blocked Cd-induced phosphorylation of c-Jun N-terminal kinase (JNK), but not
      extracellular signal-regulated kinases 1/2 and p38, in neuronal cells. Inhibition
      of JNK by SP600125 or over-expression of dominant negative c-Jun potentiated
      celastrol protection against Cd-induced cell death. Furthermore, pre-treatment
      with celastrol prevented Cd down-regulation of phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN) and activation of phosphoinositide 3'
      kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling in
      neuronal cells. Over-expression of wild-type PTEN enhanced celastrol inhibition
      of Cd-activated Akt/mTOR signaling and cell death in neuronal cells. The findings
      indicate that celastrol prevents Cd-induced neuronal cell death via targeting JNK
      and PTEN-Akt/mTOR network. Our results strongly suggest that celastrol may be
      exploited for the prevention of Cd-induced neurodegenerative disorders.
      Celastrol, a plant-derived triterpene, has shown neuroprotective effects.
      However, little is known regarding the effect of celastrol on cadmium (Cd)
      neurotoxicity. This study underscores that celastrol prevents Cd-induced neuronal
      apoptosis via inhibiting activation of JNK (c-Jun N-terminal kinase) and Akt/mTOR
      network. Celastrol suppresses Cd-activated Akt/mTOR pathway by elevating PTEN
      (phosphatase and tensin homolog). The findings suggest that celastrol may be
      exploited for the prevention of Cd-induced neurodegenerative disorders.

PMID- 24111527
TI  - Implication of potassium on the quality of cherry tomato fruits after postharvest
      during cold storage.
AB  - The influence of the potassium (K) content in tomato fruits over compounds or
      antioxidant characteristics during the postharvest period in cold storage is
      little known. The aim of this work was to determine whether the effect of a
      biofortification programme with K in KCl form can improve the postharvest storage
      of cherry tomato fruits at 4  degrees C. K treatments applied during the crop
      cycle of the plants: 5, 10 and 15 mM of KCl. Biomass parameters, levels of K,
      antioxidant capacity test, Vitamin C, carotenoids, phenolic compounds and free
      polyamines in tomato cherry fruits were measured. Our results show that the
      treatment with 15 mM KCl prevents weight and water loss during postharvest
      storage at 4  degrees C, increases K concentration, and bolsters the antioxidant
      capacity, since the concentration in lycopenes as well as flavonoids and
      derivatives rose, while the contents in Vitamin C together with hydroxycinnamic
      acids and derivatives remained stable.

PMID- 24111526
TI  - Induction of a type I interferon signature in normal human monocytes by
      gadolinium-based contrast agents: comparison of linear and macrocyclic agents.
AB  - The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages
      through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the
      mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to
      induce a type I interferon signature and a proinflammatory/profibrotic phenotype
      in normal human monocytes in vitro. Expression of genes associated with type I
      interferon signalling and inflammation and production of their corresponding
      proteins were determined. Both linear and macrocyclic GdBCA stimulated expression
      of multiple type I interferon-regulated genes and the expression of numerous
      chemokines, cytokines and growth factors in normal human peripheral blood
      monocytes. There was no correlation between the magnitude of the measured
      response and the Gd chelate used. To explore the mechanisms responsible for GdBCA
      induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal
      human dermal fibroblasts were incubated with GdBCA-treated monocyte culture
      supernatants and the effects on profibrotic gene expression were examined.
      Supernatants from monocytes exposed to all GdBCA stimulated types I and III
      collagen, fibronectin and alpha-smooth muscle actin (alpha-SMA) expression in
      normal dermal fibroblasts. The results indicate that the monocyte activation
      induced by GdBCA may be the initial step in the development of GdBCA associated
      fibrosis in NSF.

PMID- 24111529
TI  - Is there a role for day-to-day home blood pressure variability in guiding
      management of hypertension?
AB  - 1. Although two population-based studies have demonstrated the prognostic value
      of day-to-day home blood pressure (BP) variability, data are still limited. 2.
      Thresholds of normality, target levels for treatment and optimal number and times
      of home measurement needed for better assessment of day-to-day home BP
      variability also remain to be investigated. 3. Although further prospective
      studies are required, home BP is a strong and modifiable risk factor, and patient
      compliance should be encouraged.

PMID- 24111528
TI  - Predictive value of atrial high-rate episodes for arterial stiffness and
      endothelial dysfunction in dual-chamber pacemaker patients.
AB  - BACKGROUND: Various pacing studies have demonstrated an association between right
      ventricular pacing (RVp) and atrial fibrillation (AF), even after preserving
      atrioventricular (AV) synchrony. We aimed to assess the interaction between
      arterial stiffness, endothelial function and atrial high-rate episodes (AHRE) in
      patients with dual-chamber pacemakers. METHODS: We studied 101 patients with dual
      chamber pacemakers incorporated with sophisticated AF detection and therapy
      algorithms. Macrovascular endothelial dysfunction (ED) was measured by the
      relative change in aortic augmentation index (AIx), using carotid artery
      applanation tonometry in response to inhaled salbutamol and sublingual glyceryl
      trinitrate. Microvascular ED was measured by cutaneous laser Doppler flowmetry
      (LDF) in response to acetylcholine (Ach, endothelium dependent) and sodium
      nitroprusside (SNP, endothelium independent). Arterial stiffness was measured
      using carotid-femoral pulse wave velocity (PWVcf). 'Reservoir pressure' (Pr,
      MATLAB) describes the aortic 'cushioning' properties. RESULTS: Mean age of the
      cohort was 72.1 +/- 10.8 years; men (n = 69) 68.3%. Of 101 dual-chamber pacemaker
      patients, 23.8% (n = 24) had AHRE detected on the baseline pacemaker
      interrogation. PP, PWVcf and Pr were significantly higher in patients with AHRE
      compared with those without AHRE. The change in AIx with salbutamol (?% AIx Sal)
      and acetylcholine-induced changes in LDF (Delta%LDF Ach) were lower in patients
      with AHRE compared with those without AHRE. In patients with AHRE, significant
      correlations were observed between%Vp and Delta%LDF Ach (P = 0.03) as well as
      between PP and Delta%LDF Ach (P = 0.05). On multivariate analysis, PP, Pr, PWVcf
      and ?% AIx Sal remained as independent predictors of AHRE. CONCLUSION: In
      patients with dual-chamber pacemakers, both higher arterial stiffness and greater
      endothelial dysfunction independently predicted AHRE, irrespective of the degree
      (or mode) of pacing. Arterial stiffness and endothelial dysfunction may
      potentially contribute to the perpetuation of atrial arrhythmias beyond the
      adverse effects of ventricular pacing alone.

PMID- 24111531
TI  - Increased efficacy of omalizumab in atopic dermatitis patients with wild-type
      filaggrin status and higher serum levels of phosphatidylcholines.
AB  - Omalizumab, a monoclonal antibody targeting IgE, is an established therapy for
      severe allergic asthma and has shown efficacy in chronic spontaneous urticaria.
      Small-scale studies indicated some beneficial effect also in atopic dermatitis
      (AD). To evaluate the efficacy of omalizumab in AD and to identify markers
      associated with treatment response, we conducted a prospective 28-week open-label
      trial on 20 adults with moderate-to-severe AD. Our results confirm previous
      observations of a positive response in a subgroup of patients and suggest that
      responders are characterized by the absence of filaggrin mutations and altered
      lipid metabolite profiles with high levels of various glycerophospholipids. 

PMID- 24111532
TI  - Synthesis of pyrrolo(spiro-[2.3']-oxindole)-spiro-[4.3"]-oxindole via 1,3-dipolar
      cycloaddition of azomethine ylides with 3-acetonylideneoxindole.
AB  - A series of novel dispirooxindole derivatives, 3-acetyl-5-phenyl-pyrrolo(spiro
      [2.3']-1'-benzyl-oxindole)-spiro-[4.3"]-1"-benzyl-oxindoles, were synthesized via
      1,3-dipolar cycloaddition of the azomethine ylide with 3-acetonylideneoxindole in
      high regioselectivities and yields. An unusual regioselectivity was observed in
      this 1,3-dipolar cycloaddition, leading to the construction of novel
      dispirooxindole skeleton. The substituent effects on the regioselectivity were
      also investigated.

PMID- 24111533
TI  - Transformed non-Hodgkin lymphoma in the rituximab era: analysis of the NCCN
      outcomes database.
AB  - Histological transformation (HT) is a major cause of morbidity and mortality in
      patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National
      Cancer Comprehensive Network database for NHL provides a unique opportunity to
      investigate the natural history of HT in the rituximab era. 118 patients with
      biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were
      identified. Treatments for HT included autologous stem-cell transplant (auto-SCT)
      (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n
      = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto
      SCT patients aged <= 60 years (n = 24), the 2-year OS was 74%. For non
      transplanted patients aged <= 60 years (n = 19), the 2-year OS was 59%. The 2
      year OS of patients naive to chemotherapy prior to HT was superior to patients
      who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0.03). In this
      largest prospective cohort of patients of strictly defined HT in the rituximab
      era, the natural history of HT appears more favourable than historical studies.
      Younger patients who were not exposed to chemotherapy prior to HT experienced a
      prolonged survival even without transplantation. This study serves as a benchmark
      for future trials of novel approaches for HT in the Rituximab era.

PMID- 24111534
TI  - Developmental competence of oocytes isolated from surplus medulla tissue in
      connection with cryopreservation of ovarian tissue for fertility preservation.
AB  - OBJECTIVE: Evaluating the developmental competence of immature oocytes collected
      from surplus medulla tissue in connection with ovarian tissue cryopreservation
      for fertility preservation. DESIGN: Cohort comparative study. SETTING: University
      laboratory in Denmark from 2011-2012. POPULATION: 69 girls and women (0-38 years
      of age) who each had one ovary cryopreserved for fertility preservation. METHODS:
      Ovaries were obtained directly from the local hospital or from collaborating
      hospitals (two to five hours' transport on ice). Immature oocytes were aspirated
      from large antral follicles visible on the ovaries, and collected from the saline
      solution, containing surplus medulla tissue, following dissection of the ovarian
      cortical tissue for cryopreservation. The immature oocytes were cultured for 48 h
      in an EmbryoscopeTM Time-lapse System or in culture dishes overlaid with liquid
      paraffin using commercial and in-house supplemented culture media. MAIN OUTCOME
      MEASURES: Maturation rate for immature oocytes reaching metaphase II. RESULTS:
      With a maturation rate of 3.1%, only 21 of 682 immature oocytes reached metaphase
      II. Immature oocytes from ovaries that had been transported on ice for two to
      five hours performed significantly poorer than those recovered immediately after
      surgery. Addition of epidermal growth factor and follicle fluid from human small
      antral follicles to the culture medium did not augment the maturation rate.
      Immature oocytes cultured in the Embryoscope performed significantly better than
      those in conventional culture dishes. CONCLUSIONS: In vitro maturation of
      immature oocytes should only be attempted clinically from visible antral
      follicles and where the ovary is not subjected to a cooling period prior to
      recovery of immature oocytes.

PMID- 24111536
TI  - Couple communication, emotional and sexual intimacy, and relationship
      satisfaction.
AB  - Emotional and sexual aspects of intimacy in romantic relationships are important
      correlates of couples' relationship satisfaction. However, few studies have
      examined the effect of emotional and sexual aspects of intimacy on relationship
      satisfaction within the context of the interpersonal relationship processes. In
      addition, the association between emotional and sexual aspects of intimacy
      remains unclear. With a sample of 335 married couples from the Flourishing
      Families Project, the authors examined the associations between couple
      communication, emotional intimacy, sexual satisfaction, and relationship
      satisfaction, using the couple as the unit of analysis. The results of path
      analysis suggested that sexual satisfaction significantly predicted emotional
      intimacy for husbands and wives, while emotional intimacy did not appear to have
      a significant influence on sexual satisfaction. Further, mediation associations
      were suggested within as well as between spouses. Within spouses (for each
      spouse), emotional intimacy and sexual satisfaction mediated the association
      between spouses' appraisal of their partners' communication and their own
      relationship satisfaction. Gender differences were revealed in terms of how a
      spouse's perception of sexual satisfaction is associated with his or her
      partner's relationship satisfaction. In this study, although wives' relationship
      satisfaction was not associated with their husbands' sexual satisfaction,
      husbands tended to report high levels of relationship satisfaction when their
      wives reported greater sexual satisfaction. Findings suggest that both components
      of intimacy--emotional and sexual--should be comprehensively addressed in
      research and clinical work with couples.

PMID- 24111535
TI  - Intimate partner communication from the war zone: a prospective study of
      relationship functioning, communication frequency, and combat effectiveness.
AB  - This study examined (a) the association between relationship functioning prior to
      and during deployment, and the frequency of communication during deployment; and
      (b) the association between relationship functioning and depression during
      deployment and their influence on service members' ratings of duty performance.
      Participants were 144 partnered Airmen assessed immediately before and during a
      one-year high-risk deployment to Iraq. Results showed an overall high frequency
      of partner communication during deployment. High relationship distress at
      predeployment predicted lower frequency of communication during deployment.
      Changes in relationship distress from before deployment to during deployment
      independently predicted frequency of communication, above and beyond
      predeployment distress levels. Level of relationship distress and depression
      during deployment independently predicted service members' ratings of impact on
      duty performance. 

PMID- 24111537
TI  - Synthesis and characterization of a calix[4]arene amphiphilie bearing cysteine
      and uniform Au nanoparticle formation templated by its four cysteine moieties.
AB  - A novel calix[4]arene amphiphilic molecule, denoted by CCaL3, was synthesized and
      found to form a spherical micelle consisting of 12 molecules at low pH in aqueous
      solution. Furthermore, uniform Au nanoparticles with 2.0 nm in diameter were
      synthesized in aqueous solution on the template consisting of the four cysteines
      of the upper rim of CCaL3. Asymmetric field flow fractionation coupled with light
      scattering showed that there was no dispersity in the CCaL3 micellar aggregation
      number. When AuCl4(-) ions were added into the CCaL3 micelle solution, induced
      circular dichroism (ICD) appeared, indicating appearance of the structural
      chirality of the CCaL3/AuCl4(-) complex. A combination of electron microscopy and
      small-angle X-ray scattering showed that helically coiled bilayer sheets were
      formed upon addition of AuCl4(-). Subsequent reduction with the amine of cysteine
      moieties led to uniform Au nanoparticles formation with 2.0 nm in diameter on the
      micellar plate surface. The nanoparticle size was almost equal to the size of
      cavity constructed by the four cysteines on the calix[4]arene upper rim,
      indicating that the growth of Au nanoparticles was spatially controlled by the
      host-guest interaction between the cysteines and Au. 

PMID- 24111538
TI  - Minor head injury in children: evaluating written discharge advice provided by
      Scottish emergency departments.
AB  - OBJECTIVES: Emergency departments (EDs) routinely provide written information
      when a child with head injury (HI) is discharged home. This usually contains
      advice about recognizing signs of serious complications such as intracranial
      bleeding. This study evaluated the quality of discharge leaflets currently
      provided by Scottish emergency departments (EDs) by comparing them against
      written discharge advice recommended by the Scottish Intercollegiate Guideline
      Network (SIGN). METHODS: All 35 EDs in Scotland which treat children were asked
      to send a copy of the advice leaflet provided when a child with HI is discharged.
      Leaflets were evaluated by awarding scores for the inclusion of specific aspects
      of health information as recommended by SIGN. The inclusion of serious warning
      symptoms (maximum 20 points) and other advice on observation and help-seeking
      (maximum 21 points) was assessed. RESULTS: 34 EDs provided leaflets. The median
      score for including serious warning symptoms was 10/20. The median score for
      including advice regarding observation and when to seek help was 6.5/21. Several
      leaflets contained unclear or contradictory advice. CONCLUSION: Many leaflets did
      not include important information recommended by SIGN guidelines. There was
      considerable variation in the quality and clarity of written discharge advice
      provided. This may reduce the ability of parents to recognize rare but serious
      complications. It is recommended that a standardized HI information leaflet based
      on SIGN guidelines be used across all Scottish EDs.

PMID- 24111539
TI  - microRNA therapeutics in cardiovascular disease models.
AB  - Cardiovascular diseases are a major cause of human morbidity and mortality,
      posing a high socioeconomic burden on the health sector worldwide. microRNAs
      (miRNAs) constitute a new class of unique molecular regulators involved in the
      pathophysiology of a wide range of disorders. Studies in the past decade have
      identified miRNA signatures of various cardiovascular disorders and successfully
      validated miRNA-based therapeutic options in various small and a few large
      experimental cardiovascular disease models. In these models, researchers
      manipulate the expression of miRNAs and downstream signaling cascades, aiming to
      prevent and cure cardiovascular disease. Here, we review and discuss the recent
      reports on the in vivo use of miRNA animal models and miRNA therapeutic
      development as well as provide an outlook for clinical applications in the near
      future.

PMID- 24111541
TI  - Retinoic acid receptor alpha: One of plasma biomarkers associated with
      exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Exacerbation of COPD is a major risk factor for bad prognosis of
      COPD. A few plasma proteins have been discovered to associate with hospital
      admission due to exacerbation up to date. We tried to find new plasma biomarkers
      to predict the exacerbation of COPD. METHODS: We examined the plasma of normal
      control (n = 8) and COPD stable (n = 8) and exacerbation (n = 8) using 2
      Dimentional Electrophoresis. The differentially expressed protein spots were
      identified by MALDI-TOF. ELISA were performed for quantitative measurement of
      RARalpha in plasma from normal control (n = 37) and COPD (n = 35). RESULTS: 17
      proteins were differentially expressed in plasma between stable and exacerbation
      state in the subjects with COPD. Identification using MALDI-TOF showed that
      retinoic acid receptor alpha, ninein, isoform CRA_a, alpha-1 antitrypsin,
      fibrinogen gamma, tyrosyl-DNA phosphodiesterase 2, and T cell receptor delta
      chain were increased in exacerbation of COPD, while fibrin beta, Crystal
      Structure Of An Autoimmune Complex Between A Human Igm RF* And Igg1 Fc,
      transferrin, serpin peptidase inhibitor member 6, complement factor B
      preproprotein, Chain B, Crig Bound To C3c, and WD repeat-containing protein 1
      isoform 1 were decreased. Quantitative measurement showed that RARalpha plasma
      levels significantly increased in exacerbation state compared to stable state of
      COPD (n = 14). In the plasma of stable state, the COPD subjects (n = 14) having
      more than 0.4 time/yr of admission had very high levels of RAR alpha protein and
      those (n = 11) having less than 0.4 times/yr of admission had the intermediate
      levels compared to those having no exacerbation (n = 10). ROC analysis of RAR
      alpha levels to frequency of admission showed an area under the curve of 0.844. A
      cut-off of 0.154 ng/ml of RAR alpha predicted hospital admission with a
      sensitivity of 71.4% and a specificity of 92.8%. CONCLUSION: The proteomic
      analysis of plasma indicates that alteration of several proteins may be
      associated with admission of COPD. Among them, plasma RAR alpha level may predict
      hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.

PMID- 24111540
TI  - Drugs for allosteric sites on receptors.
AB  - The presence of druggable, topographically distinct allosteric sites on a wide
      range of receptor families has offered new paradigms for small molecules to
      modulate receptor function. Moreover, ligands that target allosteric sites offer
      significant advantages over the corresponding orthosteric ligands in terms of
      selectivity, including subtype selectivity within receptor families, and can also
      impart improved physicochemical properties. However, allosteric ligands are not a
      panacea. Many chemical issues (e.g., flat structure-activity relationships) and
      pharmacological issues (e.g., ligand-biased signaling) that are allosteric
      centric have emerged. Notably, the fact that allosteric sites are less
      evolutionarily conserved leads to improved selectivity; however, this can also
      lead to species differences that can hinder safety assessment. Many allosteric
      ligands possess molecular switches, wherein a small structural change (chemical
      or metabolic) can modulate the mode of pharmacology or receptor subtype
      selectivity. As the field has matured, as described here, key principles and
      strategies have emerged for the design of ligands/drugs for allosteric sites.

PMID- 24111542
TI  - Energetics of Z-DNA binding protein-mediated helicity reversals in DNA, RNA, and
      DNA-RNA duplexes.
AB  - Z-DNA binding proteins (ZBPs) specifically recognize and stabilize left-handed
      double helices, including Z-DNA and Z-RNA. However, the energetics of Z-form
      stabilization by ZBPs have never been characterized due to the technical
      limitations of bulk studies, resulting in an unclear understanding of the ZBP
      operational mechanism at the molecular level. Here, we use single-molecule
      fluorescence resonance energy transfer (FRET) to determine the energetics of Z
      form stabilization by ZBP for DNA, RNA, and DNA-RNA duplexes, revealing that the
      formation of B-Z or A-Z junctions dominates the thermodynamics and kinetics of Z
      form stabilization. Furthermore, in contrast to general assumptions, the Z-form
      is most efficiently and most rapidly formed in the DNA-RNA hybrid duplex due to
      the greatly reduced junction energy in the DNA-RNA hybrid. 

PMID- 24111544
TI  - Fluctuations in pathogenic CD4+ T-cell subsets in a murine sclerodermatous model
      of chronic graft-versus-host disease.
AB  - To determine the roles of CD4+ T-cell (Th) subsets, including Th17 cells, in the
      development of chronic graft-versus-host disease (cGVHD), we used a Th-dependent
      cGVHD model comprising B10.D2 donor and BALB/c recipient mice. The clinical GVHD
      score increased beginning at day +14, peaked at day +42, and remained elevated
      until day +70. In the skin, increased dermal thickness was apparent at day +14,
      and maintained with few changes until day +70. In contrast, the liver had peak
      pathologic scores at day +28, and the tissue damage began to improve at day +56.
      To determine possible associations between improvement of liver pathology and
      changes in Th subsets, we analyzed Th subsets using flow cytometry. Th1
      frequencies in the livers were greater than other Th subsets throughout the
      disease course, but the frequencies decreased over time. Notably, Th17 cells were
      rarely detected during earlier periods, but emerged at day +56, which correlated
      with the improved hepatic inflammation. In contrast, other Th subsets (Th2 and
      regulatory T cells) did not change significantly during the disease course. These
      results indicate the association of attenuation on cGVHD with a later emergence
      of Th17 cells and concomitant decrease of Th1 cells.

PMID- 24111543
TI  - DFT computational study of the methanolytic cleavage of DNA and RNA
      phosphodiester models promoted by the dinuclear Zn(II) complex of 1,3-bis(1,5,9
      triazacyclododec-1-yl)propane.
AB  - A density functional theory study of the cleavage of a DNA model [p-nitrophenyl
      methyl phosphate (2)] and two RNA models [p-nitrophenyl 2-hydroxypropyl phosphate
      (3) and phenyl 2-hydroxypropyl phosphate (4)] promoted by the dinuclear Zn((II))
      complex of 1,3-bis(1,5,9-triazacyclododec-1-yl)propane formulated with a bridging
      methoxide (1a) was undertaken to determine possible mechanisms for the
      transesterification processes that are consistent with experimental data. The
      initial substrate-bound state of 2:1a or 3:1a has the two phosphoryl oxygens
      bridging Zn((II))1 and Zn((II))2. For each of 2 and 3, four possible mechanisms
      were investigated, three of which were consistent with the overall free energy
      for the catalytic cleavage step for each substrate. The computations revealed
      various roles for the metal ions in the three mechanisms. These encompass
      concerted or stepwise processes, where the two metal ions with associated alkoxy
      groups [Zn((II))1:((-)OCH3) and Zn((II))1:((-)O-propyl)] play the role of a
      direct nucleophile (on 2 and 3, respectively) or where Zn((II))1:((-)OCH3) can
      act as a general base to deprotonate an attacking solvent molecule in the case of
      2 or the attacking 2-hydroxypropyl group in the case of 3. The Zn((II))2 ion can
      serve as a spectator (after exerting a Lewis acid role in binding one of the
      phosphates' oxygens) or play active additional roles in providing direct
      coordination of the departing aryloxy group or positioning a hydrogen-bonding
      solvent to assist the departure of the leaving group. An important finding
      revealed by the calculations is the flexibility of the ligand system that allows
      the Zn-Zn distance to expand from ~3.6 A in 1a to over 5 A in the transforming
      2:1a and 3:1a complexes during the catalytic event.

PMID- 24111545
TI  - Tris(phosphinoamide)-supported uranium-cobalt heterobimetallic complexes
      featuring Co -> U dative interactions.
AB  - A series of tris- and tetrakis(phosphinoamide) U/Co complexes has been
      synthesized. The uranium precursors, (eta(2)-Ph2PN(i)Pr)4U (1), (eta(2)
      (i)Pr2PNMes)4U (2), (eta(2)-Ph2PN(i)Pr)3UCl (3), and (eta(2)-(i)Pr2PNMes)3UI (4),
      were easily accessed via addition of the appropriate stoichiometric equivalents
      of [Ph2PN(i)Pr]K or [(i)Pr2PNMes]K to UCl4 or UI4(dioxane)2. Although the
      phosphinoamide ligands in 1 and 4 have been shown to coordinate to U in an eta(2)
      fashion in the solid state, the phosphines are sufficiently labile in solution to
      coordinate cobalt upon addition of CoI2, generating the heterobimetallic Co/U
      complexes ICo(Ph2PN(i)Pr)3U[eta(2)-Ph2PN(i)Pr] (5), ICo((i)Pr2PNMes)3U[eta(2)
      ((i)Pr2PNMes)] (6), ICo(Ph2PN(i)Pr)3UI (7), and ICo((i)Pr2PNMes)3UI (8).
      Structural characterization of complexes 5 and 7 reveals reasonably short Co-U
      interatomic distances, with 7 exhibiting the shortest transition metal-uranium
      distance ever reported (2.874(3) A). Complexes 7 and 8 were studied by cyclic
      voltammetry to examine the influence of the metal-metal interaction on the redox
      properties compared with both monometallic Co and heterobimetallic Co/Zr
      complexes. Theoretical studies are used to further elucidate the nature of the
      transition metal-actinide interaction. 

PMID- 24111546
TI  - Endometrial tissue and blood plasma concentration of ceftiofur and metabolites
      following intramuscular administration of ceftiofur crystalline free acid to
      mares.
AB  - REASONS FOR PERFORMING STUDY: Systemic administration of ceftiofur crystalline
      free acid (CCFA) may be a potential treatment for infectious endometritis caused
      by Streptococcus equi ssp. zooepidemicus (S.  zooepidemicus) and other
      susceptible bacterial organisms in the mare. OBJECTIVE: To determine if i.m.
      administration of CCFA at the label dose will exceed the minimum inhibitory
      concentration (MIC) of S.  zooepidemicus in the endometrium following single
      administration and multiple administration protocols. STUDY DESIGN: Experimental
      pharmacokinetic study. METHODS: Three mares (Group 1) were administered a single
      i.m. dose of CCFA (6.6 mg/kg bwt) and blood and endometrial biopsies were
      collected at selected intervals for 144 h. Six additional mares (Groups 2 and 3)
      received CCFA at times 0, 4, 11 and 18 days, and were sampled at predetermined
      times for 25 or 49 days, respectively. Plasma and tissue samples were analysed by
      high-pressure liquid chromatography with tandem mass spectrometry for
      desfuroylceftiofur acetamide concentration, which is a direct measure of all
      ceftofur and ceftiofur metabolites in the sample. RESULTS: A mean plasma
      desfuroylceftiofur acetamide concentration of 0.367 +/- 0.0162 MUg/ml (mean +/-
      s.e.) was detected at 96 h following administration. Mean endometrial tissue
      concentration was 0.510 +/- 0.0418 MUg/g at 96 h and exceeded the MIC for S. 
      zooepidemicus (0.25 MUg/ml) throughout the 144 h monitoring period for Group 1.
      Mares in Groups 2 and 3, given multiple doses of CCFA, maintained plasma
      concentrations above the MIC for S.  zooepidemicus for 25 days. Endometrial
      tissue levels remained above the MIC at most data collection points for 25 days.
      CONCLUSIONS: Ceftiofur crystalline free acid reaches appropriate endometrial
      tissue values to exceed the MIC of S.  zooepidemicus, a common cause of bacterial
      endometritis. Therefore, CCFA should be effective in the treatment of equine
      bacterial endometritis caused by S.  zooepidemicus and other susceptible
      bacterial pathogens in the mare.

PMID- 24111547
TI  - The real role of prediagnostic high-density lipoprotein cholesterol and the
      cancer risk: a concise review.
AB  - BACKGROUND: In several observational and clinical studies, the association
      between serum cholesterol levels and cancer is still unsettled although serum
      total cholesterol has been associated with increased mortality from cancer.
      Moreover, the importance of abnormal levels of serum lipid components as the main
      features of dyslipidemia and the risk of individual cancers is unclear. The
      prevalence of dyslipidemia is increasing worldwide but, the precise aetiology of
      the link between risk of cancer and the behaviour of lipid profile, prior
      diagnosis, has yet to be determinated. Low levels of high-density lipoprotein
      cholesterol (HDL) at baseline of many of the studies analyzed has to be taken
      into account, and continued low levels of HDL without explanation should be
      considered by clinicians. AIMS: The main aim of this review was to undertake the
      assessment of the most recent studies implying the lipid profile and cancer risk,
      and focused on low HDL levels at baseline and follow up, and also analyzing this
      behaviour on the different cancer types. MATERIAL AND METHODS: A literature
      search was performed to identify publications. The most recent prospective and
      case-control studies with multivariate Cox models were analyzed and also were
      considered some recent meta-analyses. RESULTS AND CONCLUSIONS: The findings
      exposed in this review suggest that the association with low HDL levels at
      baseline of different studies of cancer risk is shared among many types of
      cancer, and it is mainly linked to obesity and inflammation, suggesting a common
      pathway.

PMID- 24111548
TI  - Development of uncertainty-based work injury model using Bayesian structural
      equation modelling.
AB  - This paper proposed a Bayesian method-based structural equation model (SEM) of
      miners' work injury for an underground coal mine in India. The environmental and
      behavioural variables for work injury were identified and causal relationships
      were developed. For Bayesian modelling, prior distributions of SEM parameters are
      necessary to develop the model. In this paper, two approaches were adopted to
      obtain prior distribution for factor loading parameters and structural parameters
      of SEM. In the first approach, the prior distributions were considered as a fixed
      distribution function with specific parameter values, whereas, in the second
      approach, prior distributions of the parameters were generated from experts'
      opinions. The posterior distributions of these parameters were obtained by
      applying Bayesian rule. The Markov Chain Monte Carlo sampling in the form Gibbs
      sampling was applied for sampling from the posterior distribution. The results
      revealed that all coefficients of structural and measurement model parameters are
      statistically significant in experts' opinion-based priors, whereas, two
      coefficients are not statistically significant when fixed prior-based
      distributions are applied. The error statistics reveals that Bayesian structural
      model provides reasonably good fit of work injury with high coefficient of
      determination (0.91) and less mean squared error as compared to traditional SEM. 

PMID- 24111549
TI  - Complexities and contingencies conceptualised: towards a model of reproductive
      navigation.
AB  - Current international attention to reproductive health behaviour is inspired by a
      western celebration of individual rights, autonomous action and rational choice.
      A predominant idea is that individuals should be free to act in accordance with
      their reproductive intentions and that, in doing so, they will attain their
      desired (and quantifiable) fertility outcomes. Yet such a framework leads to a
      misrepresentation of the reproductive dynamics on the ground, because individual
      fertility intentions are often not a priori defined, decisions are often not the
      result of rational calculation and reproductive happenings do not exist in a
      social vacuum. This article provides sociocultural evidence for a different
      conceptualisation of reproductive health behaviour. On the basis of long-term
      anthropological fieldwork in the East Province of Cameroon, I will analyse the
      complexities of fertility-related decision-making. Two case studies from the
      field will show that reproductive happenings are often characterised by
      indeterminacy and contingency. In order to understand the complex ways in which
      women give direction to these uncertainties, I propose an encompassing framework
      of reproductive navigation that explicitly acknowledges the influence of
      sociality and corporeality on fertility aspirations and actions. 

PMID- 24111550
TI  - Comparison of treatment effects of guided tissue regeneration on infrabony
      lesions between animal and human studies: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: For ethical reasons it is becoming increasingly more
      difficult to obtain, from clinical studies, histological data on infrabony
      defects treated with guided tissue regeneration (GTR) techniques. The aim of this
      systematic review was to find the value of extrapolating animal data on treatment
      of periodontal infrabony lesions, using GTR only or GTR + bone grafts, to human
      clinical results. MATERIAL AND METHODS: Searches of the PubMed and Cochrane
      databases were combined with hand searching of articles published from 1 January
      1969 to 1 August 2012. The search included any type of barrier membrane, with or
      without grafted materials, used to treat periodontal infrabony lesions. All
      studies with histological or re-entry methodology outcome parameters that
      evaluated bone-filling and/or new-cementum-formation ratios from a defect depth
      were collected. When comparing animal and human outcomes, a meta-analysis was
      used to evaluate the bone-filling ratio, but only a descriptive analysis of the
      histological studies was performed. RESULTS: In total, 22 studies were selected
      for the meta-analysis. In the GTR + bone graft groups the weighted-average bone
      filling ratios were 52% (95% CI: 18-85%) in animals and 57% (95% CI: 30-83%) in
      humans, which were not statistically significantly different (p = 0.825). Similar
      results were found in the GTR-only groups, in which the weighted-average bone
      filling ratios were 54% (95% CI: 37-72%) in animals and 59% (95% CI: 42-77%) in
      humans (p = 0.703). New-cementum formation of GTR only and GTR + bone grafts
      showed comparable ratio outcomes, and both were superior to the control group in
      animals only (p = 0.042). CONCLUSION: Although quality assessments differed
      between animal and human studies, our analysis indicated that animal models and
      human results showed similar bone-filling ratios in infrabony defects treated
      with GTR only or with GTR + bone grafting.

PMID- 24111551
TI  - Gsp mutation in acromegaly and its influence on TRH-induced paradoxical GH
      response.
AB  - OBJECTIVE: We recently reported that paradoxical GH response to TRH
      administration reflects biological characteristics in patients with acromegaly.
      The aim of this study is to elucidate the relationship between gsp mutations and
      the paradoxical GH response to TRH. PATIENTS: Sixty-seven patients with
      acromegaly were included for analysis. Paradoxical increase in serum GH level to
      TRH, GH suppression by octreotide and bromocriptine, radiological profiles and
      histopathological findings were analysed with respect to tumour gsp-mutation
      status. RESULTS: Twenty-six (38.8%) gsp mutations were detected, and the number
      of paradoxical GH responders to TRH, defined as an increase of 100% or more in GH
      after TRH, was 49 (73.1%). Among the paradoxical GH responders to TRH, 21
      patients (42.9%) had a gsp mutation and 28 patients (57.1%) did not. The
      percentage of paradoxical GH responders to TRH in gsp-positive and gsp-negative
      patients was not significantly different (80.8% and 68.3%, respectively). The gsp
      positive group showed a significantly higher paradoxical increase in serum GH
      level by TRH administration (1830% vs 650% GH increase, P = 0.045) and greater GH
      suppression by octreotide (88.7% vs 75.4% GH decrease, P = 0.003) than the gsp
      negative group. CONCLUSION: Paradoxical GH response to TRH was observed
      regardless of gsp mutation, although the rate of increase was significantly
      higher in gsp-positive patients. These results suggest that gsp mutation is not
      sufficient to cause the paradoxical GH response to TRH, while other unidentified
      factors have a strong influence on paradoxical GH response to TRH in patients
      with acromegaly.

PMID- 24111552
TI  - Trifluoromethide as a strong base: [CF3-] mediates dichloromethylation of
      nitrones by proton abstraction from the solvent.
AB  - An unprecedented reactivity of CF3-TMS has been revealed, which exploits the
      basic character of the generated [CF3(-)] capable of delivering dichloromethide
      from dichloromethane with subsequent transfer to nitrones under smooth
      conditions. The proton-abstraction pathway was demonstrated through isotopic
      labeling experiments in CD2Cl2. The same reaction was achieved in acetonitrile
      with the introduction of a cyanomethyl group onto the nitrones. 

PMID- 24111553
TI  - What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high
      anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?
AB  - CONTEXT: Paracetamol (acetaminophen) ingestion is the most frequent
      pharmaceutical overdose in the developed world. Metabolic acidosis sometimes
      occurs, but the acidosis is infrequently persistent or severe. A growing number
      of case reports and case series describe high anion gap metabolic acidosis
      (HAGMA) following paracetamol exposure with subsequent detection or measurement
      of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both.
      Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn
      genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia
      in the setting of paracetamol exposure reflects an acquired or transient
      derangement of glutathione metabolism or previously unrecognized genetic defects.
      OBJECTIVE: We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria
      among patients with HAGMA in the setting of paracetamol exposure. Our goal was to
      identify any consistent features that might increase our understanding of the
      pathophysiology, diagnosis, and treatment of similar cases. METHODS: We searched
      the medical literature using PUBMED and EMBASE from inception to 28 August 2013
      applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR
      "acetaminophen"). The intersection of these two searches returned 77 articles, of
      which 64 involved human subjects and were in English. Two articles, one each in
      Spanish and Dutch, were reviewed. An additional Google Scholar search was done
      with the same terms. We manually searched the reference lists of retrieved
      articles to identify additional four relevant articles. We focused on articles
      including measured 5-oxoproline concentrations in urine or blood. RESULTS: Twenty
      two articles included quantified 5-oxoproline concentrations. Several additional
      articles mentioned only qualitative detection of 5-oxoproline in urine or blood
      without concentrations being reported. Our manual reference search yielded four
      additional articles for a total of 24 articles describing 43 patients with
      quantified 5-oxoproline concentrations. The cases varied widely in paracetamol
      dose, duration and circumstances of paracetamol exposure, presence, and degree of
      elevation in transaminase activities, and when reported observed blood, serum, or
      urine 5-oxoproline concentrations. Concomitant use of flucloxacillin, another
      medication associated with oxoprolinemia or oxoprolinuria, confounded several of
      the cases. No clear dose-response relationship existed between the quantity of
      paracetamol ingested and the observed concentrations of 5-oxoproline. Clinical
      outcomes, including mortality, varied with no clear relationship to 5-oxoproline
      concentrations. CONCLUSIONS: In rare cases, HAGMA in the setting of paracetamol
      exposure is attributable to 5-oxoprolinemia. Clinicians should first exclude
      commoner and treatable causes of HAGMA, such as lactic acidosis, co-ingested drug
      administration, and ketoacidosis. It is likely that the propensity for HAGMA
      following paracetamol exposure may be genetically determined. The effects of
      acetylcysteine on 5-oxoproline concentrations or clinical outcome are unknown.
      When HAGMA is diagnosed, the 5-oxoproline concentration and the glutathione
      synthetase activity should be measured.

PMID- 24111554
TI  - Toxicity and death following recreational use of 2-pyrrolidino valerophenone.
AB  - BACKGROUND: Consumption of substituted cathinones, frequently called 'legal
      highs' or 'designer drugs', is increasing in the European Union. In July 2012,
      the French Medicine Agency listed the substituted cathinone's chemical family as
      narcotic and psychotropic substances, to restrict their use and distribution. We
      present, here, the first documented cases of recreational use of 2-pyrrolidino
      valerophenone (PVP) associated with death for one patient, with post-mortem
      toxicological analysis. CASE REPORTS: Two men purchased the legal high Energy-3
      (NRG-3). It can be sold as laboratory reagent and is available from Internet. The
      oldest died of sudden cardiac arrest. The other experienced visual hallucinations
      and psychotic symptoms for 24 h. He also presented bilateral mydriasis, sinus
      tachycardia and rhabdomyolysis. He reported an occasional intranasal use of NRG
      3. Analysis of the powder and blood and urine from both men revealed the presence
      of PVP. DISCUSSION AND CONCLUSION: PVP belongs to the substituted cathinones
      chemical family. These cases highlight the need for emergency physicians,
      toxicologists and networks of toxicovigilance to control the use of these
      substances and their dangers, quickly identify cases of severe poisoning
      associated with the use of new drugs and to develop detection methods.

PMID- 24111555
TI  - The point process use-availability or presence-only likelihood and comments on
      analysis.
AB  - 1. Use-availability and presence-only analyses are synonyms. Both require two
      samples (one containing known locations, one containing potential locations),
      both estimate the same parameters, and both use the same fundamental likelihood.
      2. Use-availability and presence-only designs compare characteristics of points
      where an organism was located to those where the organism could have been
      located. These designs can be generalized to estimate the relative probability
      that any event occurred at a set of locations. 3. This article generalizes the
      use-availability likelihood given in Johnson et al. (Resource selection functions
      based on use-availability data: theoretical motivation and evaluation methods,
      Journal of Wildlife Management, 2006) to point locations. This derivation arrives
      at the same likelihood as Fithian & Hastie (Statistical Models for Presence-Only
      Data: Finite-Sample Equivalence and Addressing Observer Bias, 2012) but uses a
      different technique and allows a more general link function. Fithian & Hastie
      (2012) use a case-control argument and Bayes theorem to derive the likelihood.
      This article uses Lagrangian multipliers to maximize the two-sample likelihood.
      4. Resource selection functions (RSF) defined here are ratios of density
      functions. RSFs must be positive and unbounded. Proper link functions must
      provide proportionality over their entire range. Given these conditions, the
      exponential link is the most logical and appropriate link function for RSFs.
      These conditions exclude the logistic link. 5. This article affirms that
      estimation of a RSF does not involve 'running logistic regression'. By assigning
      0 and 1 (pseudo-)responses to vectors of covariates associated with locations in
      the used and available sample, it is possible to 'trick' logistic regression
      software into maximizing the use-availability likelihood. Representing the
      analysis as 'logistic regression' is misleading because that implies use of the
      logistic link, which is inappropriate for RSF's. It is more accurate to state
      that the 'use-availability likelihood was maximized'. 6. RSFs are more general,
      intuitive and useful than resource selection probability functions (RSPF). RSPFs
      depend heavily on sampling mechanisms and the number of used and available
      locations selected. Consequently, the objective of estimation in use-availability
      studies should be the RSF, not the RSPF. 7. Two simple examples and R code in the
      Supporting Information illustrate computations. These examples maximize the
      general log likelihood without the aid of logistic regression software.

PMID- 24111556
TI  - Parity effects in few-layer graphene.
AB  - We study the electronic properties in few-layer graphenes (FLGs) classified by
      even/odd layer number n. FLGs with even n have only parabolic energy dispersions,
      whereas FLGs with odd n have a linear dispersion besides parabolic ones. This
      difference leads to a distinct density of states in FLGs, experimentally
      confirmed by the gate-voltage dependence of the electric double-layer
      capacitance. Thus, FLGs with odd n are unique materials that have relativistic
      carriers originating in linear energy dispersion. 

PMID- 24111558
TI  - Leukaemia cutis at the site of a Groshong line insertion in a patient with acute
      myeloid leukaemia.

PMID- 24111559
TI  - SVR4 (suppressor of variegation 4) and SVR4-like: two proteins with a role in
      proper organization of the chloroplast genetic machinery.
AB  - SUPPRESSOR OF VARIEGATION 4 (SVR4, also called MRL7) and its homolog SVR4-like
      (also called MRL7-Like) were originally identified as important proteins for
      proper function of the chloroplast in Arabidopsis. Both are nuclear-encoded
      chloroplast-located proteins, and knockout mutants of either gene result in
      seedling lethality. Transmission electron microscopy analysis revealed that
      chloroplast development is arrested at an early developmental stage in both
      mutants. Accordingly, in the mutant plants severely decreased levels of
      photosynthetic pigments as well as subunits of the photosynthetic complexes could
      be detected. In absence of either of the two proteins chloroplast DNA
      organization was clearly affected. Immunological analysis revealed that SVR4 is a
      component of the transcriptionally active chromosome (TAC) from barley
      chloroplasts. Analyses of gene expression indicate that SVR4 and SVR4-like are
      required for proper function of the plastid transcriptional machinery. We propose
      that SVR4 and SVR4-like function as molecular chaperones ensuring proper
      organization of the nucleoids in chloroplasts. 

PMID- 24111560
TI  - Short communication: HIV type 1 tropism determination in a novel dried blood spot
      membrane and the use of a mixture of outer nested polymerase chain reaction
      primers.
AB  - Genotropism was determined in 608 Brazilian samples collected in dried blood
      spots using Polyethersulfone collection cards. Patients were infected by subtype
      B (88.8%), F (5.6%), C (3.3%), A (1.8%), and G (0.5%). All patients were exposed
      to three classes of antiretrovirals, and 59.8% of the samples harbored R5
      viruses, 35% non-R5-tropic viruses, and 5.1% harbored mixtures of R5 and non-R5
      tropic viruses, with non-R5 more prevalent among clade B-infected patients as
      compared to non-B (42.8% versus 19.1%; p<0.0003). A strategy using a mixture of
      outer nested polymerase chain reaction (PCR) primers reduced the number of
      negative PCR results from 39% to 19%.

PMID- 24111557
TI  - The central nervous system sites mediating the orexigenic actions of ghrelin.
AB  - The peptide hormone ghrelin is important for both homeostatic and hedonic eating
      behaviors, and its orexigenic actions occur mainly via binding to the only known
      ghrelin receptor, the growth hormone secretagogue receptor (GHSR). GHSRs are
      located in several distinct regions of the central nervous system. This review
      discusses those central nervous system sites that have been found to play
      critical roles in the orexigenic actions of ghrelin, including hypothalamic
      nuclei, the hippocampus, the amygdala, the caudal brain stem, and midbrain
      dopaminergic neurons. Hopefully, this review can be used as a stepping stone for
      the reader wanting to gain a clearer understanding of the central nervous system
      sites of direct ghrelin action on feeding behavior, and as inspiration for future
      studies to provide an even-more-detailed map of the neurocircuitry controlling
      eating and body weight. 

PMID- 24111561
TI  - Drawing a Waddington landscape to capture dynamic epigenetics.
AB  - Epigenetics is most often reduced to chromatin marking in the current literature,
      whereas this notion was initially defined in a more general context. This
      restricted view ignores that epigenetic memories are in fact more robustly
      ensured in living systems by steady-state mechanisms with permanent molecule
      renewal. This misconception is likely to result from misleading intuitions and
      insufficient dialogues between traditional and quantitative biologists. To
      demystify dynamic epigenetics, its most famous image, a Waddington landscape and
      its attractors, are explicitly drawn. The simple example provided, is sufficient
      to highlight the main requirements and characteristics of dynamic gene networks,
      underlying cellular differentiation, de-differentiation and trans
      differentiation. 

PMID- 24111563
TI  - Flexible insulin dosing improves health-related quality-of-life (HRQoL): a time
      trade-off survey.
AB  - PURPOSE: People with insulin-treated diabetes often face strict regimens with
      inflexible dose timing, frequent injections, and frequent self-measured blood
      glucose (SMBG) testing. The objective of this study was to estimate the health
      related quality-of-life (HRQoL) impact of these aspects using time trade-off
      (TTO) methods. METHODS: HRQoL was examined via a TTO survey in the UK, Canada,
      and Sweden with separate analyses of 2465 respondents from the general
      population, 274 people with type 1 diabetes, and 417 people with type 2 diabetes.
      Respondents evaluated health states with diabetes, SMBG testing, and basal
      injections that were once-daily time flexible, once-daily at a fixed time, and
      twice-daily at a fixed time in a basal or basal-bolus regimen. RESULTS: Time
      flexible basal injections were associated with 0.016 and 0.013 higher utility vs
      a fixed time of injection for basal-only and basal-bolus regimens, respectively,
      as evaluated by the general population. The diabetes respondents confirmed the
      basal-only results with 0.015 higher utility, but the difference in utility was
      non-significant for basal-bolus. Once-daily injections had higher utility
      compared with twice-daily injections for basal (0.039 and 0.042) and basal-bolus
      (0.022 and 0.021) regimens, as evaluated by the general population and people
      with diabetes, respectively. Increased frequency of SMBG negatively affected
      health utility. LIMITATIONS: This study has the limitation that it measures
      hypothetical health states rather than the HRQoL of people with these health
      states; furthermore, it could be suggested that the web-based nature of this
      survey is biased towards literate respondents with internet access and IT
      competence. CONCLUSIONS: Flexible dosing and fewer injections have a positive
      HRQoL impact, which potentially may enhance therapy adherence and could
      contribute to improved long-term outcomes. The impact of flexibility is greater
      in people treated with basal-only insulin regimens, and diminishes if bolus
      injections are part of the treatment regimen.

PMID- 24111562
TI  - Instrumental vaginal deliveries; are midwives safer practitioners? A
      retrospective cohort study.
AB  - OBJECTIVE: To compare obstetric morbidity of midwife-performed instrumental
      vaginal deliveries with those performed by doctors. DESIGN: Retrospective cohort
      study. SETTING: University Hospital, UK. POPULATION: Women undergoing an
      instrumental vaginal delivery of a singleton infant outside of the operating
      theater in Aberdeen Maternity Hospital, between June 2005 and June 2010. METHODS:
      Prospectively entered data were obtained from the hospital data management
      system. Obstetric outcomes of deliveries by midwives were compared with those
      performed by any doctor and, in a secondary analysis, with those by junior
      doctors (fewer than two years at 'registrar' level). Sociodemographic
      characteristics and clinical outcomes were compared using the chi-squared test,
      Mann-Whitney U-test and independent sample t-test. MAIN OUTCOME MEASURES: Third-
      or fourth-degree tears. RESULTS: Among 2540 women identified, 330 (13%) were
      delivered by midwives. Maternal and clinical characteristics were comparable in
      each group. Midwives were more likely to use ventouse as their instrument of
      choice. Women delivered by midwives were less likely to suffer a third- or fourth
      degree tears than those delivered by doctors and junior doctors. This difference
      did not reach statistical significance once adjusted for instrument used: odds
      ratio 0.6 (95% confidence interval: 0.3-1.2) and odds ratio 0.6 (95% confidence
      interval: 0.3-1.1), respectively. CONCLUSIONS: Instrumental vaginal deliveries
      performed by trained midwives are associated with equivalent maternal morbidity
      to those performed by doctors once adjusted for midwives' preference for the
      ventouse. This study highlights the potential contribution of an advanced role
      for midwives in the labor ward.

PMID- 24111564
TI  - Fabrication and mechanical characterization of semi-free-standing (conjugated)
      polymer thin films.
AB  - Polymers undergo severe low-dimensionality effects when they are confined to
      ultrathin films since most of the structural and dynamical processes involving
      polymer molecules are correlated to length scales of the order of nanometers.
      However, the real influence of the size limitation over such processes is often
      hard to identify as it is masked by interfacial effects. We present the
      fabrication of a new type of nanostructure consisting of poly[[9-(1-octylnonyl)
      9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5
      thiophenediyl] (PCDTBT) thin film that is held up exclusively over tips of
      poly(ether-ether-ketone) (PEEK) nanopillars. The fabrication method exploits the
      nonwetting behavior of PCDTBT onto an ordered PEEK nanopillar array when the
      mobility of the PCDTBT molecules is enhanced by a solvent annealing process. We
      use this new configuration to characterize the mechanical behavior of free
      standing thin film regions, thus in the absence of underlaying substrate, by
      means of an atomic force microscope (AFM) setup. First, we study how the finite
      thickness and/or the presence of the underlying substrate influences the
      mechanical modulus of the material in the linear elastic regime. Moreover, we
      analyze deep indentations up to the rupture of the thin film, which allow for the
      measurement of important mechanical features of the nanoconfined polymer, such as
      its yield strain, the rupture strain, the bending rigidity, etc., which are
      impossible to investigate in thin films deposited on substrates. 

PMID- 24111565
TI  - Beading of the astrocytic processes (clasmatodendrosis) following head trauma is
      associated with protein degradation pathways.
AB  - OBJECTIVES: To present the incidence of clasmatodendrosis (injured astrocytic
      processes) and analyse the association between clasmatodendrosis and the
      ubiquitin proteasome system (UPS) and autophagy lysosome system (autophagy).
      METHODS: The injured cerebral cortices of 36 autopsy cases were analysed by light
      microscopy by immunohistochemistry using an anti-glial fibrillary acidic protein
      (GFAP) antibody and UPS marker antibodies (ubiquitin and lysine 48-linked
      polyubiquitin chains (K(48)) and autophagy marker (lysine 63-linked polyubiquitin
      chains (K(63)), p62/sequestosome 1 and microtubule-associated protein 1 light
      chain 3 [LC3]). Double-immunofluorescence staining was used to detect the
      relationships between p62-K(48), p62-K(63) and GFAP-K(48). RESULTS:
      Clasmatodendrosis that was immunoreactive to GFAP or K(48) was detected by 1 hour
      up to 14 days following head trauma. The survival time of cases with
      clasmatodendrosis was significantly shorter than that in cases without
      clasmatodendrosis (p < 0.01). Involvement of contusion or oedema was
      significantly frequent in cases with clasmatodendrosis (p < 0.01). There was no
      significant age difference between cases with clasmatodendrosis and cases without
      clasmatodendrosis (p = 0.18). Double-immunofluorescence staining for p62-K(48)
      and GFAP-K(48) demonstrated clasmatodendrosis with overlapping fluorescence
      signals. CONCLUSION: Clasmatodendrosis is associated with UPS-mediated, autophagy
      and relatively acute pathological findings after traumatic intracranial injury.

PMID- 24111566
TI  - Photochemistry of singlet oxygen sensor green.
AB  - To detect singlet oxygen ((1)O2), the commercially available fluorescent sensor
      named Singlet Oxygen Sensor Green (SOSG) has been the most widely used from
      material studies to medical applications, for example, photodynamic therapy. In
      light of the previous studies, SOSG is a dyad composed of fluorescein and
      anthracene moieties. In the present study, we carried out quantitative studies on
      photochemical dynamics of SOSG for the first time, such as the occurrence of
      intramolecular photoinduced electron transfer (PET), (1)O2 generation, and two
      photon ionization. It was revealed that these relaxation pathways strongly depend
      on the irradiation conditions. The visible-light excitation (ex. 532 nm) of SOSG
      induced intramolecular PET as a major deactivation process (kPET = 9.7 * 10(11)
      s(-1)), resulting in fluorescence quenching. In addition, intersystem crossing
      occurred as a minor deactivation process that gave rise to (1)O2 generation via
      the bimolecular triplet-triplet energy transfer (kq = 1.2 * 10(9) M(-1) s(-1)).
      Meanwhile, ultraviolet-light excitation (355 nm) of SOSG caused the two-photon
      ionization to give a SOSG cation (Phiion = 0.003 at 24 mJ cm(-2)), leading to
      SOSG decomposition to the final products. Our results clearly demonstrate the
      problems of SOSG, such as photodecomposition and (1)O2 generation. In fact, these
      are not special for SOSG but common drawbacks for most of the fluorescein-based
      sensors. 

PMID- 24111567
TI  - Genetic isolation by environment or distance: which pattern of gene flow is most
      common?
AB  - Gene flow among populations can enhance local adaptation if it introduces new
      genetic variants available for selection, but strong gene flow can also stall
      adaptation by swamping locally beneficial genes. These outcomes can depend on
      population size, genetic variation, and the environmental context. Gene flow
      patterns may align with geographic distance (IBD--isolation by distance), whereby
      immigration rates are inversely proportional to the distance between populations.
      Alternatively gene flow may follow patterns of isolation by environment (IBE),
      whereby gene flow rates are higher among similar environments. Finally, gene flow
      may be highest among dissimilar environments (counter-gradient gene flow), the
      classic "gene-swamping" scenario. Here we survey relevant studies to determine
      the prevalence of each pattern across environmental gradients. Of 70 studies, we
      found evidence of IBD in 20.0%, IBE in 37.1%, and both patterns in 37.1%. In
      addition, 10.0% of studies exhibited counter-gradient gene flow. In total, 74.3%
      showed significant IBE patterns. This predominant IBE pattern of gene flow may
      have arisen directly through natural selection or reflect other adaptive and
      nonadaptive processes leading to nonrandom gene flow. It also precludes gene
      swamping as a widespread phenomenon. Implications for evolutionary processes and
      management under rapidly changing environments (e.g., climate change) are
      discussed.

PMID- 24111568
TI  - The genesis of collective health in Brazil.
AB  - During the 1970s in Brazil a social space directed towards health problems on the
      population level, called collective health, was created and institutionalised. To
      what extent did this Brazilian invention correspond to a specific socio
      historical practice? The works published on this topic have considered social
      medicine as a homogeneous phenomenon without empirically studying the
      specificities of national experiences. To bridge this gap, a historical study on
      the genesis of collective health in Brazil was carried out based on Bourdieu's
      field theory. The interaction between the paths of the founders and the
      conditions of historical possibilities were researched through documentary and
      bibliographical sources, as well as through in-depth interviews of the founders.
      This social space originated from a meeting of agents with different social
      backgrounds but who interconnected, creating a structure that was independent of
      each agent considered individually. One of the components of this establishment
      was the joining of theoretical production and the implementation of health
      reforms that resulted in the organisation of a universal health system. This
      study attempts to show how the international political situation and the
      contradictions of the national crisis created a universe of possibilities,
      allowing for the genesis of this sui generis space in Brazil. 

PMID- 24111569
TI  - Photophysical properties of cyclometalated Pt(II) complexes: counterintuitive
      blue shift in emission with an expanded ligand pi system.
AB  - A detailed examination was performed on photophysical properties of
      phosphorescent cyclometalated (C(^)N)Pt(O(^)O) complexes (ppy)Pt(dpm) (1),
      (ppy)Pt(acac) (1'), and (bzq)Pt(dpm) (2) and newly synthesized (dbq)Pt(dpm) (3)
      (C(^)N = 2-phenylpyridine (ppy), benzo[h]quinoline (bzq), dibenzo[f,h]quinoline
      (dbq); O(^)O = dipivolylmethanoate (dpm), acetylacetonate (acac)). Compounds 1,
      1', 2, and 3 were further characterized by single crystal X-ray diffraction.
      Structural changes brought about by cyclometalation were determined by comparison
      with X-ray data from model C(^)N ligand precursors. The compounds emit from metal
      perturbed, ligand-centered triplet states (E(0-0) = 479 nm, 1; E(0-0) = 495 nm,
      2; E(0-0) = 470 nm, 3) with disparate radiative rate constants (kr = 1.4 * 10(5)
      s(-1), 1; kr = 0.10 * 10(5) s(-1), 2; kr = 2.6 * 10(5) s(-1), 3). Zero-field
      splittings of the triplet states (DeltaE(III-I) = 11.5 cm(-1), 1'; DeltaE(III-I)
      < 2 cm(-1), 2; DeltaE(III-I) = 46.5 cm(-1), 3) were determined using high
      resolution spectra recorded in Shpol'skii matrices. The fact that the E0-0
      energies do not correspond to the extent of pi-conjugation in the aromatic C(^)N
      ligand is rationalized on the basis of structural distortions that occur upon
      cyclometalation using data from single crystal X-ray analyses of the complexes
      and ligand precursors along with the triplet state properties evaluated using
      theoretical calculations. The wide variation in the radiative rate constants and
      zero-field splittings is also explained on the basis of how changes in the
      electronic spin density in the C(^)N ligands in the triplet state alter the spin
      orbit coupling in the complexes.

PMID- 24111570
TI  - Aberrant Rac1-mineralocorticoid receptor pathways in salt-sensitive hypertension.
AB  - According to Guyton's model, impaired renal sodium excretion plays a key role in
      the increased salt sensitivity of blood pressure (BP). Several factors contribute
      to impaired renal sodium excretion, including the sympathetic nervous system, the
      renin-angiotensin system and aldosterone. Accumulating evidence suggests that
      abnormalities in aldosterone and its receptor (i.e. the mineralocorticoid
      receptor (MR)) are involved in the development of salt-sensitive (SS)
      hypertension. Patients with metabolic syndrome often exhibit hyperaldosteronism
      and are susceptible to SS hypertension. Aldosterone secretion from the adrenal
      glands is not suppressed in obese hypertensive rats fed a high-salt diet because
      of the abundant production of adipocyte-derived aldosterone-releasing factors,
      which are independent of the negative feedback regulation of aldosterone
      secretion by the renin-angiotensin-aldosterone system. Increased plasma
      aldosterone levels lead to SS hypertension via MR activation in the kidney. Renal
      MR activity is increased in Dahl salt-sensitive rats fed a high-salt diet,
      despite the appropriate suppression of plasma aldosterone levels. In this rat
      strain, activation of MR in the distal nephron causes salt-induced hypertension.
      This paradoxical response of the MR to salt loading can be attributed to
      activation of Rac1, a small GTPase. In the presence of aldosterone, activated
      Rac1 synergistically and directly activates MR in a ligand-independent manner.
      Thus, Rac1 activation in the kidney determines the salt sensitivity of BP.
      Together, the available evidence suggests that the aberrant Rac1-MR pathway plays
      a key role in the development of SS hypertension. 

PMID- 24111571
TI  - Computation and experiment reveal that the ring-rearrangement metathesis of
      Himbert cycloadducts can be subject to kinetic or thermodynamic control.
AB  - Unusual observations in the ring-rearrangement metathesis of Himbert arene/allene
      cycloadducts to form fused polycylic lactams led to a more in-depth experimental
      study that yielded conflicting results. Differences in reactivity within related
      systems and unexpected changes in diastereoselectivity among other similar
      substrates were not readily explained on the basis of the experimental results.
      Computational investigations demonstrated substrate-dependent changes in reaction
      pathways (ring-opening metathesis/ring-closing metathesis [ROM/RCM] cascade vs
      ring-closing metathesis/ring-opening metathesis [RCM/ROM] cascade). Furthermore,
      some reactions were judged to be under thermodynamic control and others under
      kinetic control. The greater understanding of the most likely reaction pathways
      and their energetics provides a reasonable explanation for the previously
      irreconcilable results. 

PMID- 24111572
TI  - Epidemiology of unintentional child injuries in the South-East Asia Region: a
      systematic review.
AB  - All the 11 members of the South-East Asia Region (SEAR) of the World Health
      Organization are categorised as low- and middle-income countries. This region has
      over a quarter of the world's total population but comprises about one-third of
      the world's unintentional injury-related deaths. There is a paucity of good
      quality mortality and morbidity data from most of these countries. This is the
      first systematic review of community-based surveys on child injuries that
      summarises evidence from child injury studies from the SEAR countries. The
      included papers reported varying estimates of overall non-fatal unintentional
      injury rates across the countries, from 15/1000 children in Thailand to as high
      as 342/1000 children in India. The fatal injury rates were also found to be
      varying. This review revealed a need for strengthening child injury research
      using standard methodologies across the region and for promoting the
      dissemination of the results. 

PMID- 24111573
TI  - Profiling viral infections in grapevine using a randomly primed reverse
      transcription-polymerase chain reaction/macroarray multiplex platform.
AB  - Crop-specific diagnostics to simultaneously detect a large number of pathogens
      provides an invaluable platform for the screening of vegetative material prior to
      its propagation. Here we report the use of what is to-date the largest published
      example of a crop-specific macroarray for the detection of 38 of the most
      prevalent or emergent viruses to infect grapevine. The reusable array consists of
      1,578 virus-specific 60 to 70mer oligonucleotide probes and 19 plant and internal
      control probes spotted onto an 18 * 7 cm nylon membrane. In a survey of 99
      grapevines from the United States and Europe, virus infections were detected in
      46 selections of Vitis vinifera, V. labrusca, and interspecific hybrids. The
      majority of infected vines (30) was singly infected, while 16 were mixed-infected
      with viruses from two or more families. Representatives of the four main virus
      families Betaflexiviridae, Closteroviridae, Secoviridae, and Tymoviridae present
      in grapevines were found alone and in combination, with a notable bias in
      representation by members of the family Tymoviridae. This work demonstrates the
      utility of the macroarray platform for the multiplex detection of viruses in a
      single crop, its potential for characterizing grapevine virus associations, and
      usefulness for rapid diagnostics of introduced material in quarantine centers or
      in certification programs.

PMID- 24111574
TI  - Geospatial and temporal analyses of Bean pod mottle virus epidemics in soybean at
      three spatial scales.
AB  - A statewide survey was carried out from 2005 through 2007 to quantify, map, and
      analyze the spatial dynamics and seasonal patterns of Bean pod mottle virus
      (BPMV) prevalence and incidence within Iowa. In all, 8 to 16 soybean fields were
      arbitrarily sampled from 96 counties in 2005 and all 99 counties in 2006 and
      2007. Field- and county-scale BPMV prevalence and incidence data were mapped
      using geographic information systems software. BPMV prevalence was highest in the
      2006 soybean growing season, when BPMV was detected in 38.7% of all soybean
      fields, 91.9% of all counties, and 100% of the agricultural climate districts.
      BPMV incidence at the field scale was highest in 2006, when mean statewide end-of
      season incidence was 24.4%. Spatial analyses indicated that BPMV incidence was
      spatially clustered at the county scale in all three growing seasons. Prevalence
      at the county scale was clustered in 2005 and 2007 but not in 2006. Semivariogram
      analyses at the field scale indicated the presence of significant (P <= 0.05)
      spatial dependence (clustering) at distances <=23.4 km in 2005, 297.7 km in 2006,
      and 45.2 km in 2007. Data for county-scale incidence displayed a north (low
      incidence) to south (high incidence) BPMV gradient in each year of the survey.
      High county-scale BPMV prevalence and incidence levels in 2006 were significantly
      associated with BPMV prevalence and incidence in 2007 (P <= 0.05). Soybean fields
      with narrow row spacings (<=38 cm) were associated with higher levels of BPMV
      incidence. Soybean fields infected with BPMV had a higher probability of
      infection by Phomopsis pod and stem blight than did non-BPMV-infected fields.
      This study provides new quantitative tools and information to better understand
      the seasonal, temporal, and geographical distribution of BPMV disease risk at
      several spatial scales.

PMID- 24111576
TI  - Role of blossom colonization in pepper seed infestation by Xanthomonas
      euvesicatoria.
AB  - Colonization of Xanthomonas euvesicatoria was investigated in pepper blossoms and
      the relationship between inoculum concentrations and seed infestation was
      determined. Inoculation of blossoms resulted in asymptomatic pepper fruit.
      However, real-time polymerase chain reaction detected X. euvesicatoria in 39% of
      the seed lots assayed and viable colonies were recovered from 35% of them.
      Successful transmission occurred in 16% of the seed lots tested. In a separate
      experiment, X. euvesicatoria reached populations of up to 1 * 10(5) CFU/blossom
      on stigmas 96 h after inoculation. Bacteria colonized stylar and ovary tissues
      with populations ranging from 1 * 10(5) to 1 * 10(6) CFU/blossom 96 h after
      inoculation. A positive correlation existed between inoculum concentration and
      percentage of infested seedlots. Blossoms inoculated with Acidovorax citrulli
      also resulted in infested pepper seedlots. Furthermore, A. citrulli colonized
      pepper blossoms significantly better than X. euvesicatoria by 96 h
      postinoculation. It was concluded that pepper blossoms can be a potential site of
      ingress for X. euvesicatoria into seed, and blossom colonization may be involved
      in pepper seed infestation. Data also indicated that seed infestation via
      blossoms may be nonspecific because nonhost plants can be colonized by
      incompatible pathogens. Thus, host-pathogen interactions may not be important for
      bacterial ingress through blossoms.

PMID- 24111575
TI  - Roles of a solo LuxR in the biological control agent Lysobacter enzymogenes
      strain OH11.
AB  - Lysobacter enzymogenes is a ubiquitous plant-associated and environmentally
      friendly bacterium emerging as a novel biological control agent of plant disease.
      This bacterium produces diverse antifungal factors, such as lytic enzymes and a
      secondary metabolite (heat-stable antifungal factor [HSAF]) having antifungal
      activity with a novel structure and mode of action. The regulatory mechanisms for
      biosynthesis of antifungal factors is largely unknown in L. enzymogenes. The solo
      LuxR proteins have been shown to be widespread, playing important roles in plant
      associated bacteria. Here, we cloned and studied a solo LuxR protein, LesR, from
      L. enzymogenes strain OH11. Overexpression but not deletion of lesR significantly
      impaired HSAF biosynthesis levels and antimicrobial activities but did not show
      visible effect on production of major lytic enzymes. Overexpression of lesR also
      led to remarkably accelerated cell aggregation and induced production of a
      melanin-like pigment in L. enzymogenes; these two phenotypes are mediated by the
      diffusible factor cell-to-cell signaling system of L. enzymogenes. The C-terminus
      helix-turn-helix domain was shown to be critical for several lesR-controlled
      functions. Overall, our study provides the first example of the roles and
      mechanisms of a solo LuxR protein in a plant-associated L. enzymogenes.

PMID- 24111577
TI  - Deferoxamine promotes osteoblastic differentiation in human periodontal ligament
      cells via the nuclear factor erythroid 2-related factor-mediated antioxidant
      signaling pathway.
AB  - BACKGROUND AND OBJECTIVE: Recently it was reported that deferoxamine (DFO), an
      iron chelator, stimulates bone formation from MG63 and mesenchymal stem cells,
      but inhibits differentiation in rat calvarial cells; however, the effect of DFO
      on osteoblastic differentiation in human periodontal ligament cells (hPDLCs) has
      not been reported. The aim of this study was to investigate the effects and the
      possible underlying mechanism of DFO on osteoblastic differentiation of hPDLCs.
      MATERIAL AND METHODS: The effect of DFO on osteoblast differentiation was
      determined by the staining intensity of calcium deposits with Alizarin red and by
      RT-PCR analysis of the expression of osteoblastic markers. Signal transduction
      pathways were analyzed by western blotting. RESULTS: DFO increased osteogenic
      differentiation in a concentration-dependent manner by expression of the mRNA for
      differentiation markers and calcium nodule formation. Exposure of hPDLCs to DFO
      resulted in increases in the production of reactive oxygen species and in the
      levels of nuclear factor erythroid 2-related factor (Nrf2) protein in nuclear
      extractions, as well as a dose-dependent increase in the expression of Nrf2
      target genes, including glutathione (GSH), glutathione S-transferase, gamma
      glutamylcysteine lygase, glutathione reductase and glutathione peroxidase.
      Pretreatment with Nrf2 small interfering RNA, GSH depletion by buthionine
      sulfoximine and diethyl maleate, and with antioxidants by N-acetylcysteine and
      vitamin E, blocked DFO-stimulated osteoblastic differentiation. Furthermore,
      pretreatment with GSH depletion and antioxidants blocked DFO-induced p38 MAPK,
      ERK, JNK and nuclear factor-kappaB pathways. CONCLUSION: These data indicate, for
      the first time, that nontoxic DFO promotes osteoblastic differentiation of hPDLCs
      via modulation of the Nrf2-mediated antioxidant pathway.

PMID- 24111578
TI  - Minute ventilation during spontaneous breathing, high-intensity noninvasive
      positive pressure ventilation and intelligent volume assured pressure support in
      hypercapnic COPD.
AB  - BACKGROUND: High-intensity noninvasive positive pressure ventilation (HI-NPPV) is
      an effective treatment option in patients with stable hypercapnic chronic
      obstructive pulmonary disease (COPD). However, the effect of HI-NPPV compared
      with spontaneous breathing (SB) on minute ventilation (MV) in patients receiving
      long-term treatment remains to be determined. This study compared MV during HI
      NPPV and SB. In addition, the ability of intelligent volume assured pressure
      support (iVAPS) to increase MV to the same extent as HI-NPPV was determined.
      METHODS: Daytime pneumotachographic measurements were performed during SB, HI
      NPPV and iVAPS. RESULTS: Twenty-seven stable hypercapnic COPD patients (mean FEV1
      34 +/- 15% predicted) who had been treated with HI-NPPV for a median of 22 months
      (interquartile range 8.5-84 months) were enrolled. Mean MV was 9.5 +/- 1.7 L/min
      during SB and 12.1 +/- 2.8 L/min during HI-NPPV, an increase of 2.5 L/min (95% CI
      [1.5-3.6] p < 0.001), or 26%. MV during iVAPS was 11.7 +/- 3.6 L/min, an increase
      of 1.8 L/min (95%CI [0.7-3.0], p = 0.003) compared with SB. There was no
      difference in MV between HI-NPPV and iVAPS (p = 0.25). CONCLUSION: Long-term HI
      NPPV increased MV by an average of 26% compared with SB in stable hypercapnic
      COPD patients. A similar increase in MV was observed during use of iVAPS.

PMID- 24111580
TI  - Gap plasmons and near-field enhancement in closely packed sub-10 nm gap
      resonators.
AB  - Pairs of metal nanoparticles with a sub-10 nm gap are an efficient way to achieve
      extreme near-field enhancement for sensing applications. We demonstrate an
      attractive alternative based on Fabry-Perot type nanogap resonators, where the
      resonance is defined by the gap width and vertical elongation instead of the
      particle geometry. We discuss the crucial design parameters for such gap plasmons
      to produce maximum near-field enhancement for surface-enhanced Raman scattering
      and show compatibility of the pattern processing with low-cost and low-resolution
      lithography. We find a minimum critical metal thickness of 80 nm and observe that
      the mode coupling from the far field increases by tapering the gap opening. We
      also show the saturation of the Raman signal for nanogap periodicities below 1
      MUm, demonstrating efficient funneling of light into such nanogap arrays. 

PMID- 24111579
TI  - Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B
      cell lymphomas.
AB  - Constitutive or aberrant signalling of the B cell receptor signalling cascade has
      been implicated in the propagation and maintenance of a variety of B cell
      malignancies. Small molecule inhibitors of Bruton tyrosine kinase (BTK), a
      protein early in this cascade and specifically expressed in B cells, have emerged
      as a new class of targeted agents. There are several BTK inhibitors, including
      ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical
      and/or clinical development of which ibrutinib is currently in phase III trials.
      Recent clinical data suggest significant activity of ibrutinib as a first in
      class oral inhibitor of BTK. This review provides an overview of ongoing clinical
      studies of BTK inhibitors.

PMID- 24111581
TI  - Effects of exploitation on an overabundant species: the lesser snow goose
      predicament.
AB  - Invasive and overabundant species are an increasing threat to biodiversity and
      ecosystem functioning world-wide. As such, large amounts of money are spent each
      year on attempts to control them. These efforts can, however, be thwarted if
      exploitation is compensated demographically or if populations simply become too
      numerous for management to elicit an effective and rapid functional response. We
      examined the influence of these mechanisms on cause-specific mortality in lesser
      snow geese using multistate capture-reencounter methods. The abundance and
      destructive foraging behaviours of snow geese have created a trophic cascade that
      reduces (sub-) Arctic plant, insect and avian biodiversity, bestowing them the
      status of 'overabundant'. Historically, juvenile snow geese suffered from density
      related degradation of their saltmarsh brood-rearing habitat. This allowed
      harvest mortality to be partially compensated by non-harvest mortality (process
      correlation between mortality sources: rho = -0.47; 90% BCI: -0.72 to -0.04).
      Snow goose family groups eventually responded to their own degradation of habitat
      by dispersing to non-degraded areas. This relaxed the pressure of density
      dependence on juvenile birds, but without this mechanism for compensation,
      harvest began to have an additive effect on overall mortality (rho = 0.60; 90%
      BCI: -0.06 to 0.81). In adults, harvest had an additive effect on overall
      mortality throughout the 42-year study (rho = 0.24; 90% BCI: -0.59 to 0.67). With
      the aim of controlling overabundant snow geese, the Conservation Order amendment
      to the International Migratory Bird Treaty was implemented in February of 1999 to
      allow for harvest regulations that had not been allowed since the early 1900s
      (e.g. a spring harvest season, high or unlimited bag limits and use of electronic
      calls and unplugged shotguns). Although harvest mortality momentarily increased
      following these actions, the increasing abundance of snow geese has since induced
      a state of satiation in harvest that has driven harvest rates below the long-term
      average. More aggressive actions will thus be needed to halt the growth and
      spread of the devastating trophic cascade that snow geese have triggered. Our
      approach to investigating the impacts of population control efforts on cause
      specific mortality will help guide more effective management of invasive and
      overabundant species world-wide.

PMID- 24111582
TI  - Testosterone replacement therapy in hypogonadal men is associated with increased
      expression of LAMP-2 (CD107b) by circulating monocytes and dendritic cells.
AB  - BACKGROUND: Accumulated experimental data indicates that androgen therapy has
      effects on inflammation and protects from autoimmune disorders. Despite this, the
      in vivo effects of testosterone replacement therapy on human antigen-presenting
      cells-for example, monocytes and dendritic cells- remain unknown. OBJECTIVE,
      DESIGN AND PATIENTS: We monitored the effects of testosterone replacement therapy
      on the number and the functionality -as assessed by the expression of CD107b
      (lysosome-associated membrane protein 2, LAMP-2)- of resting and in vitro
      stimulated peripheral blood (classical and nonclassical) monocytes and dendritic
      cells (myeloid and plasmacytoid) from hypogonadal men. RESULTS: Our results show
      that testosterone replacement therapy induces overexpression of CD107b by
      circulating monocytes and dendritic cells from hypogonadal men, both under
      resting (i.e. nonstimulated) conditions and after in vitro stimulation. CD107b
      overexpression mostly involved monocytes and in vitro stimulation with CpG
      oligodeoxynucleotides. Of note, a strong correlation was found between CD107b
      expression on monocytes and serum gonadotrophins levels. CONCLUSION: These
      results support the existence of an effect of testosterone therapy, and
      potentially also of gonadotrophins, on circulating antigen-presenting cells.

PMID- 24111583
TI  - Total synthesis of (+)-lysergic acid.
AB  - We report the enantioselective total synthesis of (+)-lysergic acid using two
      different strategies, which featured three metal-catalyzed reactions for the
      construction of the BCD three rings, involving Pd-catalyzed indole synthesis for
      the construction of the B ring, a ring-closing metathesis reaction for the
      formation of the D ring, and an intramolecular Heck reaction to forge the C ring.
      In synthetic strategy I, the synthesis was achieved in 20 steps following the
      ring construction sequence of BDC. In synthetic strategy II, the synthetic route
      was shortened to only 12 steps by following the ring construction sequence of DBC
      and using a 4-chlorotryptophan derivative for the intramolecular Heck reaction.
      Moreover, we also discussed an unsuccessful synthetic strategy. 

PMID- 24111584
TI  - Childhood psoriasis--an analysis of German health insurance data.
AB  - This study explored the epidemiology, treatment, and comorbidities of juvenile
      psoriasis in Germany using health insurance data. Psoriasis is a chronic
      inflammatory skin condition that affects approximately 2% to 3% of the world's
      population. Data were obtained from a database of approximately 6.7 million
      individuals registered with health insurance organizations throughout Germany.
      The analysis considered all individuals age 18 years and younger with psoriasis
      who were registered in 2007. Comorbidities were identified using software based
      on a morbidity-based risk adjustment model. A total of 138,338 patients with a
      diagnosis of psoriasis were identified in the database, yielding a prevalence of
      2.1%. Within this group there were 4,499 children and adolescents (<= 18 years of
      age), a prevalence of 0.4%. The prevalence ranged from 0.1% at the age of 1 year
      to 0.8% at the age of 18 years. Most of the patients were treated with topical
      corticosteroids (72.2%) and antipsoriatics (e.g., tars, psoralen; 20.0%).
      Immunosuppressants were used in 3.3% of the cases. Juvenile psoriasis was
      associated with numerous significant comorbidities such as rheumatoid arthritis
      and inflammation (2.1%); delirium, psychosis, and psychotic and dissociative
      disorder (1.1%); and heart disease (0.6%). Our study demonstrated that psoriasis
      is more prevalent in children and adolescents than some older international
      investigations have documented. Analysis of the health insurance data showed that
      juvenile psoriasis is associated with a range of comorbidities. The data also may
      suggest an unrecognized burden of mental health problems in young persons with
      psoriasis.

PMID- 24111586
TI  - Hidden loss: a qualitative explorative study of children living with a parent
      with acquired brain injury.
AB  - PRIMARY OBJECTIVE: The purpose of this study was to listen to and learn from
      children showing high levels of post-traumatic stress symptoms after parental
      acquired brain injury (ABI), in order to achieve an in-depth understanding of the
      difficulties the children face in their everyday lives and identify possible
      trauma-related feelings and relational losses. DESIGN: The study was qualitative,
      using a phenomenological approach. METHODS AND PROCEDURE: Fourteen children
      between 7-14 years of age were interviewed at home using a semi-structured
      interview guide. Siblings were also invited to participate. RESULTS: All children
      were affected by their parents' ABI and the altered family situation. The
      children's expressions led the authors to identify six themes, including fear of
      losing the parent, distress and estrangement, chores and responsibilities, hidden
      loss, coping and support. The main finding indicates that the children
      experienced numerous losses, many of which were often suppressed or neglected by
      the children to protect the ill parents. CONCLUSIONS: The findings indicated that
      the children seemed to make a special effort to hide their feelings of loss and
      grief in order to protect the ill parent. These findings contribute to a deeper
      understanding of the traumatic process of parental ABI that some children
      experience and emphasize the importance of family-centred interventions that
      include the children.

PMID- 24111587
TI  - Awake intubation and awake prone positioning of a morbidly obese patient for
      lumbar spine surgery.
AB  - We describe the awake fibreoptic intubation followed by awake prone positioning
      of a woman weighing 180 kg with body mass index of 62 kg.m(-2) requiring
      emergency lumbar discectomy for cauda equina syndrome. This approach was taken to
      overcome difficulties in transfering an anaesthetised patient on to the operating
      table. Following topical anaesthesia with lidocaine and low-dose remifentanil
      infusion, oral intubation was performed using a split oral airway to guide the
      fibrescope. The patient positioned herself on the Jackson operating table,
      following which general anaesthesia was induced. This technique optimised
      protection of the patient's eyes and other pressure areas while preventing undue
      cardiorespiratory compromise. The patient tolerated the procedure well, and later
      confirmed that she would consent to undergoing the same procedure again if
      further surgery became necessary.

PMID- 24111588
TI  - Modeling phenotypic plasticity in growth trajectories: a statistical framework.
AB  - Phenotypic plasticity, that is multiple phenotypes produced by a single genotype
      in response to environmental change, has been thought to play an important role
      in evolution and speciation. Historically, knowledge about phenotypic plasticity
      has resulted from the analysis of static traits measured at a single time point.
      New insight into the adaptive nature of plasticity can be gained by an
      understanding of how organisms alter their developmental processes in a range of
      environments. Recent advances in statistical modeling of functional data and
      developmental genetics allow us to construct a dynamic framework of plastic
      response in developmental form and pattern. Under this framework, development,
      genetics, and evolution can be synthesized through statistical bridges to better
      address how evolution results from phenotypic variation in the process of
      development via genetic alterations. 

PMID- 24111585
TI  - Molecular processes that drive cigarette smoke-induced epithelial cell fate of
      the lung.
AB  - Cigarette smoke contains numerous chemical compounds, including abundant reactive
      oxygen/nitrogen species and aldehydes, and many other carcinogens. Long-term
      cigarette smoking significantly increases the risk of various lung diseases,
      including chronic obstructive pulmonary disease and lung cancer, and contributes
      to premature death. Many in vitro and in vivo studies have elucidated mechanisms
      involved in cigarette smoke-induced inflammation, DNA damage, and autophagy, and
      the subsequent cell fates, including cell death, cellular senescence, and
      transformation. In this Translational Review, we summarize the known pathways
      underlying these processes in airway epithelial cells to help reveal future
      challenges and describe possible directions of research that could lead to better
      management and treatment of these diseases. 

PMID- 24111590
TI  - Initiation of vascular development.
AB  - The initiation of vascular development occurs during embryogenesis and the
      development of lateral organs, such as lateral roots and leaves. Understanding
      the mechanism underlying the initiation of vascular development has been an
      important goal of plant biologists. Auxin flow is a crucial factor involved in
      the initiation of vascular development. In addition, recent studies have
      identified key factors that regulate the establishment of vascular initial cells
      in embryos and roots. In this review, we summarize the recent findings in this
      field and discuss the initiation of vascular development. 

PMID- 24111589
TI  - Single tryptophan and tyrosine comparisons in the N-terminal and C-terminal
      interface regions of transmembrane GWALP peptides.
AB  - Hydrophobic membrane-spanning helices often are flanked by interfacial aromatic
      or charged residues. In this paper, we compare the consequences of single Trp ->
      Tyr substitutions at each interface for the properties of a defined transmembrane
      helix in the absence of charged residues. The choice of molecular framework is
      critical for these single-residue experiments because the presence of "too many"
      aromatic residues (more than one at either membrane-water interface) introduces
      excess dynamic averaging of solid state NMR observables. To this end, we compare
      the outcomes when changing W(5) or W(19), or both of them, to tyrosine in the
      well-characterized transmembrane peptide acetyl-GGALW(5)(LA)6LW(19)LAGA-amide
      ("GWALP23"). By means of solid-state (2)H and (15)N NMR experiments, we find that
      Y(19)GW(5)ALP23 displays similar magnitudes of peptide helix tilt as
      Y(5)GW(19)ALP23 and responds similarly to changes in bilayer thickness, from DLPC
      to DMPC to DOPC. The presence of Y(19) changes the azimuthal rotation angle rho
      (about the helix axis) to a similar extent as Y(5), but in the opposite
      direction. When tyrosines are substituted for both tryptophans to yield
      GY(5,19)ALP23, the helix tilt angle is again of comparable magnitude, and
      furthermore, the preferred azimuthal rotation angle rho is relatively unchanged
      from that of GW(5,19)ALP23. The extent of dynamic averaging increases marginally
      when Tyr replaces Trp. Yet, importantly, all members of the peptide family having
      single Tyr or Trp residues near each interface exhibit only moderate and not
      highly extensive dynamic averaging. The results provide important benchmarks for
      evaluating conformational and dynamic control of membrane protein function. 

PMID- 24111593
TI  - Using textured PDMS to prevent settlement and enhance release of marine fouling
      organisms.
AB  - The antifouling efficacy of a series of 18 textured (0.2-1000 MUm) and non
      textured (0 MUm) polydimethylsiloxane surfaces with the profiles of round- and
      square-wave linear grating was tested by recording the settlement of fouling
      organisms in the laboratory and in the field by monitoring the recruitment of a
      multi-species fouling community. In laboratory assays, the diatoms Nitzschia
      closterium and Amphora sp. were deterred by all surface topographies regardless
      of texture type. Settlement of propagules of Ulva sp. was lower on texture sizes
      less than the propagule size, and settlement of larvae of Saccostrea glomerata
      and Bugula neritina was lower on texture sizes closest to, but less than, the
      sizes of larvae. After a six month field trial, all textured surfaces lost their
      deterrent effect; however, the foul-release capabilities of textures were still
      present. High initial attachment was correlated with most fouling remaining after
      removal trials, indicating that fouling organisms recruited in higher numbers to
      surfaces upon which they attached most strongly. 

PMID- 24111594
TI  - Dissolution and pharmacokinetics of baicalin-polyvinylpyrrolidone coprecipitate.
AB  - OBJECTIVES: Baicalin-polyvinylpyrrolidone coprecipitate was prepared with the aim
      of improving the dissolution and bioavailability of the baicalin. METHODS: The
      dissolution of the coprecipitate in capsule form was tested and compared with
      baicalin active pharmaceutical ingredient (API) capsules. A sensitive high
      performance liquid chromatography-ultraviolet detection method was established to
      determine the concentration of baicalin in plasma. The liquid-liquid extraction
      and solid phase extraction methods were used to pretreat the baicalin plasma
      sample. The pharmacokinetics of the coprecipitate capsules were tested and
      compared with the API capsules in six beagle dogs after crossover oral
      administration. KEY FINDINGS: The results of the dissolution demonstrated that
      the dissolution of the coprecipitate capsules was 21.02, 2.02 and 3.29 times that
      of the API capsules in 0.1 mol/l HCl solution, pH 4.5 solution and water,
      respectively, but it was slightly lower than that of the API capsules in a pH 6.8
      solution. The calibration curve showed a good linearity at concentrations between
      3.648 ng/mL and 364.8 ng/mL (r = 0.998). The baicalin plasma sample was
      successfully pretreated, with endogenous impurities almost completely removed.
      The pharmacokinetics of the coprecipitate capsules and the API capsules indicated
      that the mean values of Cmax were 127.04 +/- 10.6 and 27.49 +/- 36 MUg/l, and
      those of AUC(0-24h) were 1080.23 +/- 336.43 and 337.84 +/- 127.64 MUg/l * h,
      respectively. Compared with the baicalin API capsules, the relative
      bioavailability of the coprecipitate capsules was 338.2% +/- 93.2%. CONCLUSIONS:
      From these observations of improved dissolution and pharmacokinetic behaviours, a
      good relationship was found in vitro and in vivo, indicating that the
      coprecipitate could be a promising formulation strategy for insoluble baicalin.

PMID- 24111595
TI  - Hydrogen peroxide content and pH of expired breath condensate from patients with
      asthma and COPD.
AB  - BACKGROUND: Oxidative stress is implicated in the pathogenesis of asthma and
      chronic obstructive pulmonary disease (COPD). Analysis of the expired breath
      condensate (EBC) has been suggested to provide non-invasive inflammatory markers
      that reflect oxidative stress in the airways. OBJECTIVE: The present study
      attempts to elucidate whether the hydrogen peroxide (H2O2) levels and pH values
      in EBC may be useful as biomarkers of the activity or severity of asthma and
      COPD. METHODS: We measured the H2O2 levels and pH values using a derivatives of
      reactive oxygen metabolites exhalation test kit (Diacron) and a pH analyser,
      respectively, in EBC obtained using an EcoScreen from 29 patients with asthma, 33
      with COPD, and 33 healthy individuals (all non-smokers). We then examined the
      relationships among oxidative stress and the asthma control test (ACT) or COPD
      assessment test (CAT) scores, pulmonary function, fractional exhaled nitric oxide
      (FeNO), and the extent of low attenuation areas on HRCT. RESULTS: The H2O2 levels
      were elevated and pH was lower in both asthma (H2O2; 8.75 +/- 0.88 MUM, p < 0.01,
      pH; 7.14 +/- 0.07, p < 0.05) and COPD (H2O2; 7.44 +/- 0.89 MUM, p < 0.01, pH;
      6.87 +/- 0.10, p < 0.01) compared with control subjects (H2O2; 3.42 +/- 0.66 MUM,
      pH; 7.35 +/- 0.04). Neither the H2O2 levels nor pH correlated with the ACT scores
      and FeNO in asthma patients. Neither the H2O2 levels nor pH significantly
      correlated with the pulmonary function in asthma and COPD. However, the CAT
      scores significantly correlated with the H2O2 levels in patients with COPD (r =
      0.52, p < 0.01). CONCLUSIONS: These findings suggest that oxidative stress is
      involved in the pathogenesis of asthma and COPD and that the H2O2 levels in EBC
      might reflect the health status in COPD.

PMID- 24111596
TI  - Synthetic peptides from heat-shock protein 65 inhibit proinflammatory cytokine
      secretion by peripheral blood mononuclear cells from rheumatoid arthritis
      patients.
AB  - 1. Rheumatoid arthritis (RA) is a systemic autoimmune disease mediated by T
      cells. Proinflammatory cytokines plays a critical role in the pathogenesis of RA.
      The aim of the present study was to investigate the effects of synthetic peptides
      (HP-R1, HP-R2 and HP-R3), derived from the sequence of 65 kDa mycobacterial heat
      shock protein (HSP), on the proliferation of and cytokine secretion by peripheral
      blood mononuclear cells (PBMC) from RA patients. 2. The PBMC were obtained from
      RA patients and collected by Ficoll-Hypaque density centrifugation. Peripheral
      blood mononuclear cells were treated with one of the three synthetic peptides for
      4 h, after which time proliferation and cytokine production were determined. The
      effects of the three peptides on the proliferation of PBMC were analysed by the
      colorimetric cell proliferation (CCK-8) assay. Cytokine production was measured
      in culture supernatants using specific ELISAs. 3. None of the three peptides had
      any significant effect on the proliferation of PBMC from healthy controls.
      However, the proliferation of PBMC from RA patients was inhibited by all three
      peptides. The production of tumour necrosis factor-alpha from RA patients was
      significantly inhibited by all three peptides. The secretion of interferon-gamma
      was significantly suppressed by HP-R1 and HP-R2. Unlike the other two peptides,
      HP-R2 increased the secretion of interleukin (IL)-4. None of the peptides had any
      significant effect on the production of IL-10. 4. The results of the present
      study suggest that the synthetic peptides derived from HSP65 exhibit
      antiproliferative and anti-inflammatory activity, and support the potential use
      of synthetic peptides as therapeutic drugs in RA patients.

PMID- 24111597
TI  - Thinking about think tanks in health care: a call for a new research agenda.
AB  - Little sociological attention has been given to the role of think tanks in health
      policy and planning. Existing work in political science and public administration
      tends to define and categorise think tanks and situate them as a disinterested
      source of policy expertise. Despite the increasingly visible presence of think
      tanks in the world of health care, such work has done little to reveal how they
      operate, by whom and to what ends. Our article seeks to redress this firstly by
      examining why they have remained relatively hidden in academic analyses and
      secondly by advocating an interpretive approach that incorporates think tanks
      within the wider landscape of health policy and planning. In contrast to most
      existing literature, an interpretive approach acknowledges that much of the messy
      business of healthcare policy and planning remains hidden from view and that much
      can be gleaned by examining the range of organisations, actors, coalitions,
      everyday activities, artefacts and interactions that make up the think tank stage
      and that work together to shape health policy and planning. Given the paucity of
      research in this area, we urge the medical sociology community to open the field
      to further academic scrutiny. 

PMID- 24111598
TI  - The rules of engagement: comparing two social protest movements on YouTube.
AB  - Social media Web sites such as YouTube offer activists unique opportunities to
      reach out to new audiences through a variety of diverse appeals. Yet the rules of
      engagement on social media should depend on the structures, goals, and
      characteristics of the movements engaging in this outreach. To explore how
      differences in social movements translate into online activism, we employ a
      paired case study approach, comparing YouTube artifacts for two political
      mobilizations: the Occupy Movement and California's Proposition 8 ballot
      initiative concerning same sex marriage. Across movements, we examine the
      popularity of videos and their characteristics, and whether the type of video
      consistently predicts video engagement. We find that "social media activism" is
      not a unitary phenomenon; the two mobilizations produced unique YouTube
      ecologies. Occupy Wall Street videos tended on average to produce less engagement
      and focused on filmed live events and amateur content. Meanwhile, Proposition 8
      videos usually produced more engagement and bridged more diverse formats: from
      professionalized and scripted content to live event footage and unscripted
      monologues to the camera. Therefore, our study suggests that social activism in
      online spaces such as YouTube is not easily defined, but is adapted to suit
      movement needs-which makes social media a popular and flexible venue for activism
      but also highlights the challenges for scholars studying such venues.

PMID- 24111599
TI  - Compulsive use of social networking sites in Belgium: prevalence, profile, and
      the role of attitude toward work and school.
AB  - A representative sample (n=1,000) of the Belgian population aged 18 years and
      older filled out an online questionnaire on their Internet use in general and
      their use of social networking sites (SNS) in particular. We measured total time
      spent on the Internet, time spent on SNS, number of SNS profiles, gender, age,
      schooling level, income, job occupation, and leisure activities, and we
      integrated several psychological scales such as the Quick Big Five and the
      Mastery Scale. Hierarchical multiple regression modeling shows that gender and
      age explain an important part of the compulsive SNS score (5%) as well as
      psychological scales (20%), but attitude toward school (additional 3%) and income
      (2.5%) also add to explained variance in predictive models of compulsive SNS use.

PMID- 24111600
TI  - Video game use and cognitive performance: does it vary with the presence of
      problematic video game use?
AB  - Action video game players have been found to outperform nonplayers on a variety
      of cognitive tasks. However, several failures to replicate these video game
      player advantages have indicated that this relationship may not be
      straightforward. Moreover, despite the discovery that problematic video game
      players do not appear to demonstrate the same superior performance as
      nonproblematic video game players in relation to multiple object tracking
      paradigms, this has not been investigated for other tasks. Consequently, this
      study compared gamers and nongamers in task switching ability, visual short-term
      memory, mental rotation, enumeration, and flanker interference, as well as
      investigated the influence of self-reported problematic video game use. A total
      of 66 participants completed the experiment, 26 of whom played action video
      games, including 20 problematic players. The results revealed no significant
      effect of playing action video games, nor any influence of problematic video game
      play. This indicates that the previously reported cognitive advantages in video
      game players may be restricted to specific task features or samples. Furthermore,
      problematic video game play may not have a detrimental effect on cognitive
      performance, although this is difficult to ascertain considering the lack of
      video game player advantage. More research is therefore sorely needed.

PMID- 24111601
TI  - Evolving pattern of platelet P2Y12 inhibition in patients with acute coronary
      syndromes.
AB  - Dual antiplatelet therapy consisting of clopidogrel in addition to aspirin has
      previously been the standard of care for patients with acute coronary syndromes
      (ACS) but international guidelines have been evolving over the last 4 years with
      the introduction of prasugrel and ticagrelor. In October 2009, prasugrel was
      approved in the UK by the National Institute of Health and Clinical Excellence
      (NICE) for use in patients with ST-elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PCI), diabetic patients
      with non-ST-elevation (NSTE) ACS undergoing PCI and patients with stent
      thrombosis while other ACS patients were to continue receiving clopidogrel.
      Ticagrelor was approved in October 2011 by NICE for use in patients with moderate
      to-high risk NSTE ACS and STEMI undergoing primary PCI and was recommended in
      preference to clopidogrel in European guidelines. These recommendations were
      adopted in our region, constituting a population of 1.8 million. We studied the
      effect of changing patterns of P2Y12 inhibitor usage on levels of platelet
      inhibition during maintenance therapy. Patients admitted to Northern General
      Hospital, Sheffield, with NSTE ACS or STEMI managed with primary PCI were
      enrolled over two periods of time: May 2010 to November 2011 (T1); and October
      2012 to February 2013 (T2). Venous blood samples were obtained at 1 month after
      the onset of ACS. Light transmittance aggregometry (LTA) was performed and
      maximum aggregation response to ADP 20 MUM was determined. A total of 116
      patients were enrolled in T1 of whom 82 were receiving clopidogrel and 34 were
      receiving prasugrel. Twenty-nine patients were enrolled in T2, all of whom were
      receiving ticagrelor. Mean LTA results according to treatment with clopidogrel,
      prasugrel and ticagrelor were 57 +/- 18%, 41 +/- 20%, and 31 +/- 12%,
      respectively. Prasugrel was associated with significantly lower platelet
      aggregation responses than clopidogrel (p < 0.001) and ticagrelor was associated
      with significantly lower platelet aggregation responses than both prasugrel (p =
      0.015) and clopidogrel (p < 0.001). We conclude that international guidelines and
      NICE approval have led to increasing levels of P2Y12 inhibition in ACS patients
      in this UK centre between May 2010 and February 2013. Ticagrelor was associated
      with significantly greater P2Y12 inhibition than both clopidogrel and prasugrel
      during maintenance therapy.

PMID- 24111602
TI  - On the characterization of the surface chemistry of quantum dots.
AB  - The interaction of ligands with the surface of quantum dots (QD) was studied
      using tritiated oleic acid as an ultrasensitive reporter. The use of labeled
      oleic acid not only permitted to quantify the number of ligands attached to the
      surface of QDs of various sizes but also enabled the investigation of the
      relative affinity of different ligand types for the nanocrystal's surface. 

PMID- 24111603
TI  - A laboratory comparison of the performance of the buddy liteTM and enFlowTM fluid
      warmers.
AB  - Maintenance of normothermia is crucial to avoid patient morbidity. Newly released
      fluid warming devices have become smaller in size, but this change might impair
      efficacy. We performed an evaluation of the buddy liteTM and enFlowTM fluid
      warmers. We measured inflow and outlet temperatures of the devices at flow rates
      between 25 and 100 ml.min(-1) using saline at room temperature or cooled to 10 
      degrees C. At a flow rate of 25 ml.min(-1) , the outlet temperature of the buddy
      lite was significantly higher than that of the enFlow (p < 0.0001), but at flow
      rates of 75 and 100 ml.min(-1) , it was significantly lower (p < 0.0001). This
      pattern was the same for both room temperature and cooled saline. There was a
      significant drop in the temperature of saline along the length of a 1-m outflow
      tube. We conclude that both devices provide effective fluid warming at a low flow
      rate, although the heating capability of the buddy lite is limited at high flow
      rates.

PMID- 24111604
TI  - Parenting a child with a traumatic brain injury: experiences of parents and
      health professionals.
AB  - OBJECTIVE: To qualitatively explore the experiences, challenges and needs of
      parents of children with traumatic brain injury (TBI) in order to inform future
      intervention research through incorporation of participant knowledge and
      experience. METHODS: Parents of children with TBI (n = 10) and experienced health
      professionals in paediatric rehabilitation (n = 5) took part in focus groups or
      individual interviews. Audio recordings were transcribed verbatim and an
      inductive thematic analysis performed. FINDINGS: Participants reported that,
      beyond the impact of the injury on the child, TBI affects the entire family.
      Parents need to adjust to and manage their child's difficulties and can also
      experience significant emotional distress, relationship discord and burden of
      care, further adding to the challenges of the parenting role. Parents can feel
      isolated and the importance of empowerment, support and information was
      emphasized. Coping styles of disengagement and avoidance were often reported,
      despite acknowledgement that these were not beneficial. CONCLUSIONS: Parenting
      interventions may provide essential support for parents in adjusting to and
      managing their child's difficulties and the efficacy of existing programmes needs
      evaluation. Addressing parent emotional adjustment and coping strategies is vital
      following paediatric TBI, given the impact on parent well-being and the potential
      negative effects on child outcomes through reduced parenting effectiveness. Group
      programmes may enable connection and support.

PMID- 24111606
TI  - Fitness consequences of outcrossing in a social spider with an inbreeding mating
      system.
AB  - Inbreeding mating systems are uncommon because of inbreeding depression. Mating
      among close relatives can evolve, however, when outcrossing is constrained.
      Social spiders show obligatory mating among siblings. In combination with a
      female-biased sex ratio, sib-mating results in small effective populations. In
      such a system, high genetic homozygosity is expected, and drift may cause
      population divergence. We tested the effect of outcrossing in the social spider
      Stegodyphus dumicola. Females were mated to sib-males, to a non-nestmate within
      the population, or to a male from a distant population, and fitness traits of F1s
      were compared. We found reduced hatching success of broods from between
      population crosses, suggesting the presence of population divergence at a large
      geographical scale that may result in population incompatibility. However, a lack
      of a difference in offspring performance between inbred and outbred crosses
      indicates little genetic variation between populations, and could suggest recent
      colonization by a common ancestor. This is consistent with population dynamics of
      frequent colonizations by single sib-mated females of common origin, and
      extinctions of populations after few generations. Although drift or single
      mutations can lead to population divergence at a relatively short time scale, it
      is possible that dynamic population processes homogenize these effects at longer
      time scales. 

PMID- 24111605
TI  - Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation
      and lung tissue destruction.
AB  - The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold
      increased lung cancer risk even after adjusting for cigarette smoking, suggesting
      that common pathways are operative in both diseases. Although the role of the
      tyrosine kinase c-Src is established in lung cancer, less is known about its
      impact in other lung diseases, such as COPD. This study examined whether c-Src
      activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette
      smoke increased c-Src activity in human small airway epithelial (SAE) cells from
      healthy donors and in the lungs of exposed mice. Similarly, higher c-Src
      activation was measured in SAE cells from patients with COPD compared with
      healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition
      prevented epidermal growth factor (EGF) receptor signaling in response to
      cigarette smoke but not EGF stimulation. Further studies showed that cigarette
      smoke acted through protein kinase C alpha to trigger c-Src to phosphorylate EGF
      receptor and thereby to induce mitogen-activated protein kinase responses in
      these cells. To further investigate the role of c-Src, A/J mice were orally
      administered the specific Src inhibitor AZD-0530 while they were exposed to
      cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation,
      decreased macrophage influx, and prevented airspace enlargement in the lungs of
      cigarette smoke-exposed mice. Moreover, inhibiting Src deterred the cigarette
      smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar
      macrophages and lung expression of cathepsin K, IL-17, TNF-alpha, MCP-1, and KC,
      all key factors in the pathogenesis of COPD. These results indicate that
      activation of the proto-oncogene c-Src by cigarette smoke promotes processes
      linked to the development of COPD. 

PMID- 24111607
TI  - Tissue regeneration after bark girdling: an ideal research tool to investigate
      plant vascular development and regeneration.
AB  - Regeneration is a common strategy for plants to survive the intrinsic and
      extrinsic challenges they face through their life cycle, and it may occur upon
      wounding. Bark girdling is applied to improve fruit production or harvest bark as
      medicinal material. When tree bark is removed, the cambium and phloem will be
      peeled off. After a small strip of bark is removed from trees, newly formed
      periderm and wound cambium develop from the callus on the surface of the trunk,
      and new phloem is subsequently derived from the wound cambium. However, after
      large-scale girdling, the newly formed sieve elements (SEs) appear earlier than
      the regenerated cambium, and both of them derive from differentiating xylem cells
      rather than from callus. This secondary vascular tissue regeneration mainly
      involves three key stages: callus formation and xylem cell dedifferentiation; SEs
      appearance and wound cambium formation. The new bark is formed within 1 month in
      poplar, Eucommia; thus, it provides high temporal resolution of regenerated
      tissues at different stages. In this review, we will illustrate the morphology,
      gene expression and phytohormone regulation of vascular tissue regeneration after
      large-scale girdling in trees, and also discuss the potential utilization of the
      bark girdling system in studies of plant vascular development and tissue
      regeneration.

PMID- 24111608
TI  - A trade-off between quantity and quality of offspring in haematophagous
      ectoparasites: the effect of the level of specialization.
AB  - Theory predicts an adaptive trade-off between quantity and quality of offspring
      if mothers can reliably predict the offspring environment. We studied egg
      production and quality of offspring in two flea species (host-specialist
      Parapulex chephrenis and host-generalist Xenopsylla ramesis) exploiting eight
      rodent species. We evaluated quality of new imagoes via their developmental time,
      size (length of a femur as a proxy) and resistance to starvation without a blood
      meal. We predicted that the offspring quality would increase with (i) a decrease
      in the number of eggs produced by mothers and (ii) an increase in phylogenetic
      distance between maternal host and principal host of a flea. We also predicted
      that negative relationships between offspring quality and either maternal egg
      production effort or phylogenetic distance between maternal host and the
      principal host or both would be manifested stronger in host-opportunistic than in
      host-specific fleas. The highest number of eggs produced per female flea was
      accompanied by the longest duration of development and the smallest offspring in
      X. ramesis, while P. chephrenis that hatched from larger clutches survived for
      less time under starvation. Although there was no significant effect of host
      species on any dependent variable, association between offspring quality and
      phylogenetic distance of the maternal host from the principal host of a flea was
      found in X. ramesis (but not P. chephrenis) with new imagoes being larger if
      their maternal hosts were phylogenetically distant from the principal host. Our
      results demonstrated stronger trade-off between quantity and quality of offspring
      in a generalist than in a specialist flea, supporting the association between
      life-history plasticity and generalist feeding strategy. 

PMID- 24111609
TI  - Factitious Cushing's syndrome masquerading as Cushing's disease.
AB  - CONTEXT: Factitious Cushing's syndrome is extremely rare. The diagnosis is
      challenging as cross-reactivity of synthetic corticosteroids or their metabolites
      in immunoassay measurements of plasma or urinary cortisol can make distinguishing
      between true and factitious Cushing's syndrome difficult. Adrenocorticotropin
      (ACTH) is usually suppressed in factitious Cushing's syndrome. PATIENT: A 54-year
      old woman presented with clinical and biochemical features of Cushing's syndrome
      and an unsuppressed ACTH concentration. She denied recent exogenous
      corticosteroid use. INVESTIGATIONS AND RESULTS: Initial investigations revealed a
      markedly elevated urinary free cortisol, mildly elevated midnight salivary
      cortisol and normal morning cortisol concentration. Plasma ACTH was not
      suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior
      petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone
      ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified
      discordance between the urinary free and morning plasma cortisol concentrations.
      Further investigation of this discordance using high-pressure liquid
      chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free
      cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200
      nmol/24 h. CONCLUSIONS: Factitious Cushing's syndrome can mimic endogenous ACTH
      dependent hypercortisolism during initial investigations and IPSS. This case
      highlights the importance of (i) recognizing the significance of discordant
      results; (ii) using an ACTH assay capable of reliably differentiating ACTH
      dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that
      IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent
      Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS
      was essential in reaching the correct diagnosis.

PMID- 24111610
TI  - Levels of interleukin-18 and endothelin-1 in children with Henoch-Schonlein
      purpura: a study from northern India.
AB  - Henoch-Schonlein purpura (HSP) is an acute systemic vasculitis with unknown
      etiology, although several studies have found HSP to be related to cytokines such
      as tumor necrosis factor alpha, interleukin (IL)-1, and adhesion molecules. In
      the present study we determined the levels of cytokines such as IL-18 and
      endothelin-1 (ET-1) in children with HSP. Subjects were divided into three groups
      (group 1, 20 subjects with HSP; group 2, 10 subjects belonging to group 1 during
      their follow-up 4 to 6 months later; and group 3, 16 controls who were healthy
      siblings of the subjects). IL-18 and ET-1 levels were determined using enzyme
      immunoassay and expressed as mean +/- standard deviation. We observed higher IL
      18 levels in children with HSP (767.6 +/- 145.1 pg/mL) than in controls (614.6 +/
      66.54 pg/mL, p > 0.05), but IL-18 levels were found to be significantly lower in
      subjects with HSP in remission (502.7 +/- 60.81 pg/mL) than in those who were in
      an active phase (1,050 +/- 244.5 pg/mL, p < 0.05, n = 10). ET-1 levels were found
      to be significantly higher in subjects with HSP (1.93 +/- 0.19 pg/mL) than in
      controls (1.10 +/- 0.13 pg/mL, p < 0.05), although no significant difference was
      observed in ET-1 levels between subjects in group 1 (1.88 +/- 0.30 pg/mL) and
      group 2 (1.91 +/- 0.120, p > 0.05, n = 10). A positive correlation was observed
      between IL-18 and ET-1 levels in subjects with HSP (correlation coefficient [r] =
      0.5254, p < 0.01). These results suggest that levels of IL-18 and ET-1 are worth
      monitoring during the clinical course of the disease, but caution must be
      exercised in extrapolating data based on small study samples. 

PMID- 24111612
TI  - Silicon acceleration of a tandem alkene isomerization/electrocyclic ring-opening
      of 2-methyleneoxetanes to alpha,beta-unsaturated methylketones.
AB  - The first rearrangement of 2-methyleneoxetanes to alpha,beta-unsaturated
      methylketones is reported. It is proposed that when these substrates are heated,
      the corresponding oxetenes are formed and subsequently undergo electrocyclic ring
      opening to methyl vinylketones. In particular, alpha-silyl-alpha,beta-unsaturated
      methylketones were isolated in moderate to high yields and with high
      stereoselectivities. Based on the proposed mechanism, density functional theory
      explains the differential kinetics and stereoselectivities among substrates. 

PMID- 24111613
TI  - Transverse fundal uterine incision for delivery of extremely low birth-weight
      infants.
AB  - Caesarean section of extremely low birth-weight (ELBW) infants is sometimes
      challenging for obstetricians. To date, there have been no standard types of
      uterine incision to achieve an atraumatic birth for ELBW fetuses with the
      placenta covering the whole anterior uterine wall. We present seven cases of
      transverse fundal uterine incision to avoid incision into the placenta. All the
      seven cases had successful en caul deliveries (the mean birth weight, 619 +/- 213
      g), accompanied by good neonatal conditions. Transverse fundal uterine incision
      may be a safe and feasible caesarean technique in ELBW infants when incision into
      the placenta is otherwise unavoidable.

PMID- 24111611
TI  - Genetics on a WHIM.
AB  - We initially described the WHIM syndrome based on the combination of Warts,
      Hypogammaglobulinaemia, Infections and Myelokathexis (neutrophil retention in the
      bone marrow). Translational research led to the discovery that this rare
      immunodeficiency disease is caused by a heterozygous mutation in the CXCR4 gene.
      Recently, Plerixafor has been suggested as a treatment for WHIM syndrome due to
      its efficacy as a CXCR4 antagonist, closing the translational research loop. In
      this review, we will focus on the clinical manifestations, pathophysiology,
      diagnosis and possible therapies for this rare entity. 

PMID- 24111615
TI  - Hollow colloidosomes prepared using accelerated solvent evaporation.
AB  - We demonstrate a new, scalable, simple, and generally applicable two-step method
      to prepare hollow colloidosomes. First, a high volume fraction oil-in-water
      emulsion was prepared. The oil phase consisted of CH2Cl2 containing a hydrophobic
      structural polymer, such as polycaprolactone (PCL) or polystyrene (PS), which was
      fed into the water phase. The water phase contained poly(vinylalcohol), poly(N
      isopropylacrylamide), or a range of cationic graft copolymer surfactants. The
      emulsion was rotary evaporated to rapidly remove CH2Cl2. This caused
      precipitation of PCL or PS particles which became kinetically trapped at the
      periphery of the droplets and formed the shell of the hollow colloidosomes.
      Interestingly, the PCL colloidosomes were birefringent. The colloidosome yield
      increased and the polydispersity decreased when the preparation scale was
      increased. One example colloidosome system consisted of hollow PCL colloidosomes
      stabilized by PVA. This system should have potential biomaterial applications due
      to the known biocompatibility of PCL and PVA. 

PMID- 24111616
TI  - Glycomic analysis by glycoprotein immobilization for glycan extraction and liquid
      chromatography on microfluidic chip.
AB  - Glycosylation is one of the most common protein modifications and profoundly
      regulates many biological processes. Aberrant glycosylation is reported to
      associate with diseases such as cancers, human immunodeficiency virus, and immune
      disorders. It is considerably important to study protein glycosylation and the
      associated glycans for diagnostics and disease prognostics. Unlike other protein
      modifications, glycans attached to proteins are enormously complex. Therefore,
      the comprehensive analysis of glycans from biological or clinical samples is an
      unmet technical challenge. Development of the high-throughput method will
      facilitate the glycomics analysis. In this study, we developed a novel method for
      the high-throughput analysis of N-glycans from glycoproteins using glycoprotein
      immobilization for glycan extraction (GIG) coupled with liquid chromatography
      (LC) in an integrated microfluidic platform (chipLC). The separated glycans were
      then analyzed by mass spectrometry. Briefly, proteins were first immobilized on a
      solid support. Glycans on immobilized glycoproteins were modified on solid phase
      to increase the detection and structure analysis. N-Glycans were then
      enzymatically released and subsequentially separated by porous graphitized carbon
      particles packed in the same device. By applying the GIG-chipLC for glycomic
      analysis of human sera, we identified N-glycans with 148 distinct N-glycan
      masses. The platform was used to analyze N-glycans from mouse heart tissue and
      serum. The extracted N-glycans from tissues indicated that unique unsialylated N
      glycans were detected in tissues that were missing from the proximal or distal
      serum, whereas common N-glycans from tissues and serum have mature and sialylated
      structures. The GIG-chipLC provides a simple and robust platform for glycomic
      analysis of complex biological and clinical samples. 

PMID- 24111617
TI  - Combined effect of smoking and occupational exposure to dusts, gases or fumes on
      the incidence of COPD.
AB  - To assess risk factors related to the development of chronic obstructive
      pulmonary disease (COPD) including smoking and occupational exposure (OE) to
      dusts, gases or fumes, we performed a longitudinal 11-year follow-up postal
      survey. The original study population was a random population sample of 8000
      inhabitants of Helsinki aged 20 to 69 years in 1996. Participants of the first
      postal questionnaire were invited to this follow-up survey in 2007 with 4302
      (78%) answers obtained. Cumulative incidence of COPD in 11 years was 3.43%
      corresponding to an incidence rate of 3.17/1000/year after exclusion of those
      with self-reported physician-diagnosed COPD and ever COPD in 1996. Smoking and
      age, but not gender, were associated with incident COPD. Reported family history
      of COPD increased the cumulative incidence to 8.55% vs 3.04% among those without
      a family history (p < 0.001). In multivariate analysis, significant independent
      risk factors for incident COPD were: current smoking in 1996 (OR 4.40 [95% CI
      2.89-6.71]), age over 50 (OR 3.42 [95% CI 2.22-5.26]), family history of COPD (OR
      2.08 [1.27-3.43]), ever asthma (OR 2.28 [1.35-3.86]), and self-reported OE (OR
      2.14 [1.50-3.05]). Occupational exposure to dusts, gases or fumes, assessed both
      based on self-reported exposure and a job exposure matrix using reported
      professions, was an independent risk factor for incident COPD. Smoking and OE
      together yielded an additive effect on incidence of COPD.

PMID- 24111618
TI  - Elevated concentrations of CCR7 ligands in patients with eosinophilic pneumonia.
AB  - BACKGROUND: Previous studies suggest that dendritic cells and macrophages play an
      important role in inflammation of eosinophilic pneumonia. The mechanism of
      dendritic cell and macrophage accumulation into the lung, however, is unknown.
      Here, we hypothesized that CCR7 ligands, CCL19 and CCL21, contribute to the
      accumulation of dendritic cells and alveolar macrophages in the inflamed lung of
      patients with eosinophilic pneumonia. METHODS: Concentrations of the CCR7 ligands
      as well as CCL16, CCL17 and CCL22 in the bronchoalveolar lavage fluid of 53
      patients with eosinophilic pneumonia, 29 patients with sarcoidosis, 18 patients
      with idiopathic pulmonary fibrosis and 12 healthy volunteers were measured by
      enzyme-linked immunosorbent assay. Cell sources of CCR7 ligands and CCR7
      expressing cells in the bronchoalveolar lavage fluid were evaluated by
      immunocytochemistry. RESULTS: CCL19 and CCL21 levels in the bronchoalveolar
      lavage fluid were significantly higher in patients with eosinophilic pneumonia
      than in controls. Levels of CCL19, but not CCL21, were statistically correlated
      with the levels of CCL16, CCL17 and CCL22 in patients with eosinophilic
      pneumonia. Immunocytochemistry revealed CCL19 expression in dendritic cells,
      macrophages and T-lymphocytes harvested from patients with eosinophilic
      pneumonia, and CCR7 expression in dendritic cells and macrophages. Levels of
      CCL19, but not CCL21, were significantly decreased after remission in patients
      with eosinophilic pneumonia. After provocation tests, CCL19 levels were elevated
      in all patients with eosinophilic pneumonia. CONCLUSIONS: These findings indicate
      that CCL19 rather than CCL21 may contribute to the accumulation of dendritic
      cells and macrophages in the inflamed lungs of patients with eosinophilic
      pneumonia.

PMID- 24111619
TI  - Underlying pathways for interferon risk to type II diabetes mellitus.
AB  - It has been known that chronic liver treatments interfere with blood glucose
      metabolism. It was recognized that diabetes mellitus among chronic hepatitis C
      was greater in other types of chronic liver diseases. Hepatitis C directly
      promotes insulin resistance through the proteosomal degradation of insulin
      resistance substrate. It suppressed hepatocyte glucose uptake through down
      regulation of surface expression of glucose transporter. Long-term exposure to
      cytokine over expression seems to be cytotoxic to both beta cells of the pancreas
      and to hepatocytes. Elevated tumor necrosis factor-a, or its neutralization,
      increased insulin sensitivity. Interferon-a may also elevate the serum level of
      interleukin-1 which is cytotoxic to pancreatic islet cells. Both diabetes
      mellitus and resistance to interferon-a therapy are abnormally mediated by over
      expression of suppressor of cytokine signaling-1 in hepatocytes of chronic
      hepatitis C patients. CONCLUSION: These data suggest that interferon-a therapy
      should be administered with caution in patients showing any predisposition to
      Diabetes mellitus. Anti inflammatory therapy is critically recommended as a
      protector against disease development due to cytokine mediated Diabetes mellitus
      during hepatitis C therapy, since inflammation seems to be a main candidate to
      interferon suspected diabetogenesis.

PMID- 24111620
TI  - Oxytocin and diabetes mellitus: a strong biochemical relation. Review.
AB  - Oxytocin (OXT) is a neurohypophysial hormone which is synthesized in the
      paraventricular and supraoptic nuclei of the hypothalamus. OXT is currently
      attracting considerable attention because it has been discovered that it
      regulates various functions of behavior especially in the context of social
      interactions. OXT is a key component in bone formation, glycemia, male sexuality,
      cardiac differentiation and pregnancy and thus it is important to be further
      explored. The authors review various aspects of gestational diabetes, including
      definition, screening, diagnostic procedures, complications, clinical evaluation,
      indications of delivery and neonatal aspects. Not only the relation among
      diabetes mellitus, oxytocin and neurophysiology concerning erectile dysfunction,
      but also the role of OXT in the activity of arginine and vasopressin is
      investigated. It is imperative to develop technological and experimental methods
      that will be able to reveal the oxytocin and its potential. 

PMID- 24111621
TI  - Antidiabetic oils.
AB  - Many studies have demonstrated evidence of the health benefits of natural
      products. Plant extracts have been tested on a variety of physiological
      disorders, including diabetes mellitus. Studies have tested aqueous extracts,
      plant fractions extracts, families of active of compounds, and specific active
      compounds. In this review, we describe the antidiabetic effects of vegetable
      oils. Information was collected from ScienceDirect and PubMed databases using the
      following key words: Diabetes mellitus, Oils, Vegetable oils, Type 1 diabetes,
      type 2 diabetes, antidiabetic effect, antihyperglycemic, antidiabetic oil. We
      have compiled approximately ten vegetable oils with including experimental
      studies that have demonstrated benefits on diabetes mellitus. There are soybean,
      argan, olive, palm, walnut, black cumin, safflower, Colocynth, Black seed, Rice
      bran, Cinnamom, and Rocket oils. For each vegetable oil, we investigated on the
      plant's traditional uses, their pharmacological activities and their antidiabetic
      effects. It seems that many vegetable oils are really interesting and can be used
      in the improvement of human health, particularly, to prevent or to treat diabetes
      mellitus complications. 

PMID- 24111622
TI  - Interdomain dynamics explored by paramagnetic NMR.
AB  - An ensemble-based approach is presented to explore the conformational space
      sampled by a multidomain protein showing moderate interdomain dynamics in terms
      of translational and rotational motions. The strategy was applied on a complex of
      calmodulin (CaM) with the IQ-recognition motif from the voltage-gated calcium
      channel Ca(v)1.2 (IQ), which adopts three different interdomain orientations in
      the crystal. The N60D mutant of calmodulin was used to collect pseudocontact
      shifts and paramagnetically induced residual dipolar couplings for six different
      lanthanide ions. Then, starting from the crystal structure, pools of
      conformations were generated by free MD. We found the three crystal conformations
      in solution, but four additional MD-derived conformations had to be included into
      the ensemble to fulfill all the paramagnetic data and cross-validate optimally
      against unused paramagnetic data. Alternative approaches led to similar
      ensembles. Our "ensemble" approach is a simple and efficient tool to probe and
      describe the interdomain dynamics and represents a general method that can be
      used to provide a proper ensemble description of multidomain proteins.

PMID- 24111623
TI  - The effectiveness of a proactive coping intervention targeting self-management in
      diabetes patients.
AB  - OBJECTIVE: The study's aim was to investigate psychological, behavioral and
      medical long-term outcomes of an existing self-management intervention targeting
      the development of proactive coping skills (e.g. goal setting and identifying
      barriers) in type 2 diabetes patients. The study aimed to replicate prior
      research showing the intervention's effectiveness, and to extend it by (a) adding
      booster sessions and (b) prolonging the period of follow-up measurement to
      capture long-term effects. DESIGN/OUTCOME MEASURES: A total of 141 type 2
      diabetes patients were included in the intervention. The intervention employed a
      5-step approach to target proactive coping skills. Psychological (e.g. proactive
      coping and self-efficacy) and behavioural variables (e.g. self-care, diet and
      physical activity) were assessed at baseline (T1), after the initial phase of the
      intervention (T2), after the booster phase (T3) and at follow-up (T4), comprising
      a total period of 15 months. Medical variables were assessed at T1 and T4.
      RESULTS: Employing piecewise Latent Growth Curve Modelling, results showed that
      participants improved on all psychological and behavioural variables during the
      initial phase and maintained these improvements over 12 months. The booster phase
      yielded no further improvements. Mixed findings were obtained on medical
      outcomes. CONCLUSION: The original intervention is effective, but the added value
      of the booster sessions is uncertain.

PMID- 24111624
TI  - Sex-specific patterns of morphological diversification: evolution of reaction
      norms and static allometries in neriid flies.
AB  - The consequences of sex-specific selection for patterns of diversification remain
      poorly known. Because male secondary sexual traits are typically costly to
      express, and both costs and benefits are likely to depend on ambient environment
      and individual condition, such traits may be expected to diversify via changes in
      reaction norms as well as the scaling of trait size with body size (static
      allometry). We investigated morphological diversification within two species of
      Australian neriid flies (Telostylinus angusticollis, Telostylinus lineolatus) by
      rearing larvae from several populations on larval diets varying sixfold in
      nutrient concentration. Mean body size varied among populations of T.
      angusticollis, but body size reaction norms did not vary within either species.
      However, we detected diversification of reaction norms for body shape in males
      and females within both species. Moreover, unlike females, males also diversified
      in static allometry slope and reaction norms for static allometry slope of sexual
      and nonsexual traits. Our findings reveal qualitative sex differences in patterns
      of morphological diversification, whereby shape-size relationships diversify
      extensively in males, but remain conserved in females despite extensive evolution
      of trait means. Our results highlight the importance of incorporating plasticity
      and allometry in studies of adaptation and diversification. 

PMID- 24111625
TI  - CD30 expression by bone marrow mast cells from different diagnostic variants of
      systemic mastocytosis.
AB  - AIMS: CD30 expression by bone marrow (BM) mast cells (MC) has been reported
      recently in systemic mastocytosis (SM) patients. The aim of this study was to
      investigate the potential diagnostic and prognostic value of CD30 expression in
      SM as assessed by multiparameter flow cytometry. METHODS AND RESULTS: A total of
      163 consecutive BM samples corresponding to 142 SM patients and 21 non
      mastocytosis cases were studied. CD30 was positive in most SM patients (80%), but
      in only one non-mastocytosis case (4.8%). When combined with CD25, CD30
      contributed to an improved accuracy over that of CD25 alone (98% versus 93%)
      mainly because most (eight of nine) of the well-differentiated SM (WDSM), who
      lacked CD25, were CD30(+). Similar levels of expression of CD30 were observed
      among all different subgroups of SM except mast cell leukaemia; among indolent SM
      (ISM) patients, no significant association was observed between the levels of
      CD30 expression and other clinical and biological features of the disease.
      CONCLUSIONS: The increased expression of CD30 associated with absence of CD25
      contributes to the diagnosis of WDSM and its distinction from other subtypes of
      SM. By contrast, CD30 expression did not contribute either to prognostic
      stratification of ISM or to the differential diagnosis between ISM and aggressive
      SM cases.

PMID- 24111626
TI  - Optimization of the pattern visual evoked potential (VEP) in the visually-normal
      and mild traumatic brain injury (mTBI) populations.
AB  - PRIMARY OBJECTIVE: The purpose of this study was to assess the effect of check
      size (CS) and contrast (C) on VEP amplitude and latency in visually-normal (VN)
      and in mild traumatic brain injury (mTBI) adults to develop an optimized test
      protocol in each group. RESEARCH DESIGN AND METHODS: Subjects were comprised of
      VN (n = 19) and individuals with mTBI (n = 16). Full-field, pattern VEP testing
      was employed with three different CSs (10, 20 and 40 min arc) and at two C levels
      (20 and 85%). RESULTS: There was a significant effect of CS and C on the VEP
      amplitude and latency in both groups. The 20 min arc CS at both contrast levels
      produced the largest VEP amplitude, in conjunction with normative latency values,
      in both populations. There was a significant differential effect of CS and C on
      VEP responses in the visually symptomatic vs. asymptomatic mTBI sub-groups. A
      significant correlation was found between time since their most recent brain
      injury and VEP amplitude for the 20 min arc CS at low contrast. CONCLUSIONS: Use
      of the 20 min arc CS at both contrast levels represents an optimized clinical VEP
      test protocol in both the VN and mTBI groups. This protocol is rapid, high yield,
      and targeted for each diagnostic group.

PMID- 24111627
TI  - The effects of individualistic-collectivistic value orientations on non-fatal
      suicidal behavior and attitudes in Turkish adolescents and young adults.
AB  - This study aimed at investigating the effects of individualistic-collectivistic
      value orientations on non-fatal suicidal behavior and attitudes in Turkish
      adolescents and young adults. A questionnaire containing measures of
      individualism, collectivism (INDCOL), non-fatal suicidal behaviors and suicidal
      attitudes was used to collect the data. The results showed that both suicidal
      ideation and attempts were significantly more frequent in participants classified
      as individualist than those who were classified as collectivist on the basis of
      INDCOL scale scores. Participants with individualistic tendencies displayed more
      permissive attitudes toward suicide than those with collectivistic tendencies but
      collectivists believed to a greater extent than the individualists that people
      should communicate suicidal problems to others. Participants with collectivistic
      tendencies showed more accepting and helping reactions to an imagined suicidal
      friend than those with individualistic tendencies. Suicidal ideation and attempts
      were more common among adolescents than young adults. The findings suggest that
      individualistic and collectivistic value orientations and developmental status
      specific stressors play a role in the distribution of nonfatal suicidal behavior
      and the nature of suicidal attitudes. 

PMID- 24111629
TI  - When would I use medical therapies for the treatment of primary
      hyperparathyroidism?
AB  - Although there may be controversy surrounding the indications for
      parathyroidectomy in primary hyperparathyroidism, it remains the only accepted
      definitive therapy. However, even if parathyroidectomy is indicated, some
      patients refuse surgery, are medically unfit or have residual or recurrent
      disease inaccessible to further surgery. Some of these patients may be suitable
      for long-term observation but others require intervention for management of
      symptomatic or moderate to severe hypercalcaemia, loss of bone mineral density or
      renal calculi. The selection of a suitable therapy for each patient should be
      individualized. 

PMID- 24111630
TI  - The organisation of musical semantic memory: evidence from false memories for
      familiar songs.
AB  - By adapting a well-known paradigm for studying memory for words-the Deese
      Roediger-McDermott or DRM paradigm (Deese, 1959, Roediger & McDermott, 1995)-the
      two experiments reported here explore memory for song titles and song clips.
      Participants were presented with five song titles (Experiment 1a) or five 30
      second song clips (Experiment 1b) for each of nine popular artists (e.g., Robbie
      Williams). The most popular song identified for each artist in a pilot task was
      omitted from the sets of titles/clips. Following a distractor task, participants
      were asked to write down as many of the songs as they could recall. They were
      also asked to return a week later and complete a second recall task. Participants
      falsely recalled a significant number of the related but non-presented songs in
      both experiments and this increased a week later, while correct recall for
      presented items decreased. The results are discussed in terms of theory for
      musical memory as well as in the context of providing a novel method for
      exploring the organisation of musical memory.

PMID- 24111628
TI  - Fine tuning and efficient T cell activation with stimulatory aCD3 nanoarrays.
AB  - Anti-CD3 (aCD3) nanoarrays fabricated by self-assembled nanopatterning combined
      with site-directed protein immobilization techniques represent a novel T cell
      stimulatory platform that allows tight control over ligand orientation and
      surface density. Here, we show that activation of primary human CD4+ T cells,
      defined by CD69 upregulation, IL-2 production and cell proliferation, correlates
      with aCD3 density on nanoarrays. Immobilization of aCD3 through nanopatterning
      had two effects: cell activation was significantly higher on these surfaces than
      on aCD3-coated plastics and allowed unprecedented fine-tuning of T cell response.

PMID- 24111631
TI  - Influence of multi-lumen extensions on fluid flow through intravenous cannulae.
AB  - Multi-lumen extensions used to infuse multiple fluids via a single intravenous
      cannula might increase resistance and so limit the flow that can be achieved. We
      constructed low-pressure and high-pressure models and compared the effect of two
      different multi-lumen extensions on flow rate. Both multi-lumen extensions
      reduced flows by up to 76% (p < 0.001). The effect was greatest with large
      cannulae and in the high-pressure model, with the longer and narrower extension
      most impeding flow. Multi-lumen extensions can therefore significantly impede
      fluid flow, and should be avoided or removed when rapid infusion is required.
      These effects are less important in paediatric anaesthesia where smaller cannulae
      are used. Manufacturers should include internal diameter or flow effects on the
      packaging of these extensions to assist clinicians in making such decisions.

PMID- 24111632
TI  - Second autologous transplant as salvage therapy in multiple myeloma.
AB  - High-dose chemotherapy followed by autologous haematopoetic stem cell
      transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM).
      Unfortunately, there are no randomized clinical studies examining the role of a
      second ASCT in patients who relapse after the initial autotransplant. Analysing
      all available retrospective studies, it seems that salvage ASCT can safely be
      performed in most patients with an overall treatment-related mortality rate <5%.
      Approximately 65% of patients will achieve an objective response and progression
      free and overall survival will be around 12 months and 32 months, respectively.
      Retrospective data suggest that patients with a progression-free survival of >=18
      months after initial ASCT are most likely to benefit from a salvage
      autotransplant. However, patients with a <12-month duration of response after
      initial ASCT should not be considered for a second autograft in the relapsed
      setting because this group will probably only experience ASCT-related toxicity
      without any clinical benefit. Quality of response after initial ASCT and number
      of therapies preceding salvage ASCT may also have a predictive value.
      Importantly, these findings need to be verified by randomized clinical trials in
      order to firmly integrate salvage ASCT into a global therapeutic concept for
      myeloma patients including optimized induction, consolidation, and maintenance
      approaches. 

PMID- 24111633
TI  - Characterization of a bifunctional enzyme with (p)ppGpp-hydrolase/synthase
      activity in Leptospira interrogans.
AB  - Alarmone Guanosine 5'-diphosphate (or 5'-triphosphate) 3'-diphosphate [(p)ppGpp]
      is the key component that globally regulates stringent control in bacteria. There
      are two homologous enzymes, RelA and SpoT in Escherichia coli, which are
      responsible for fluctuations in (p)ppGpp concentration inside the cell, whereas
      there exists only a single RelA/SpoT enzyme in Gram-positive bacteria. We have
      identified a bifunctional enzyme with (p)ppGpp-hydrolase/synthase activity in
      Leptospira interrogans. We show that the relLin gene (LA_3085) encodes a protein
      that fully complements the relA/spoT double mutants in E. coli. The protein
      functions as a (p)ppGpp degradase as well as a (p)ppGpp synthase when the cells
      encounter amino acid stress and deprivation of carbon sources. N-terminus HD and
      RSD domains of relLin (relLinN ) were observed to restore growth of double
      mutants of E. coli. Finally, We demonstrate that purified RelLin and RelLinN show
      high (p)ppGpp synthesis activity in vitro. Taken together, our results suggest
      that L. interrogans contain a single Rel-like bifunctional protein, RelLin ,
      which plays an important role in maintaining the basal level of (p)ppGpp in the
      cell potentially contributing to the regulation of bacterial stress response.

PMID- 24111635
TI  - Cervical IL-6 and pIGFBP-1 and the prediction of neonatal outcome in symptomatic
      preterm labour.
AB  - OBJECTIVE: To evaluate the use of cervical Interleukin 6 (IL-6) and
      phosphorylated Insulin Growth Binding Protein 1 (pIGFBP1) in the prediction of
      adverse neonatal outcome. METHODS: Prospective observational study including
      women between 24 and 34 weeks of gestation. One hundred and twelve cervical
      samples for IL-6 and pIFBP1 were taken. Neonatal outcome variables were birth
      weight, Apgar scores at 1st/5th minute, gestational age at delivery, admission to
      neonatal unit (NNU) and to neonatal intensive care unit (NICU), composite
      neonatal morbidity (NCM) and neonatal mortality. RESULTS: Cervical IL-6
      concentrations (pg/ml) were higher in neonates admitted to NNU and NICU versus
      non-admission, and women developing chorioamnionitis versus non-chorioamnionitis
      (mean +/- standard deviation: 168.1 +/- 205.2 versus 62.3 +/- 72.4, p < 0.01;
      262.1 +/- 298 versus 92 +/- 127.6, p < 0.01, and 564 +/- 213 versus 93.4 +/-
      126.4, p < 0.05, respectively). In the NCM group, the IL-6 concentrations were
      higher compared to the non-NCM (181.7 +/- 224 versus 84.1 +/- 117.7, p < 0.05).
      In the preterm births <37 weeks, no differences were found for NCM, admission to
      NICU/NNU. The logistic regression analysis, showed cervical IL-6 and examination
      to-delivery interval as predictors of NCM in the univariate analysis. However,
      the only independent marker of adverse neonatal outcome was the examination-to
      delivery interval. CONCLUSIONS: Adverse neonatal outcome is associated with
      increased cervical IL-6 concentrations.

PMID- 24111634
TI  - Viral antibody dynamics in a chiropteran host.
AB  - Bats host many viruses that are significant for human and domestic animal health,
      but the dynamics of these infections in their natural reservoir hosts remain
      poorly elucidated. In these, and other, systems, there is evidence that seasonal
      life-cycle events drive infection dynamics, directly impacting the risk of
      exposure to spillover hosts. Understanding these dynamics improves our ability to
      predict zoonotic spillover from the reservoir hosts. To this end, we followed
      henipavirus antibody levels of >100 individual E. helvum in a closed, captive,
      breeding population over a 30-month period, using a powerful novel antibody
      quantitation method. We demonstrate the presence of maternal antibodies in this
      system and accurately determine their longevity. We also present evidence of
      population-level persistence of viral infection and demonstrate periods of
      increased horizontal virus transmission associated with the pregnancy/lactation
      period. The novel findings of infection persistence and the effect of pregnancy
      on viral transmission, as well as an accurate quantitation of chiropteran
      maternal antiviral antibody half-life, provide fundamental baseline data for the
      continued study of viral infections in these important reservoir hosts.

PMID- 24111636
TI  - Usefulness of plasma B-type natriuretic peptide as a prognostic marker of cardiac
      function in senile systemic amyloidosis and in familial amyloidotic
      polyneuropathy.
AB  - OBJECTIVE: In senile systemic amyloidosis (SSA), a common age-related
      amyloidosis, wild-type transthyretin accumulates in tissues, with a primary
      result being cardiac dysfunction. Here, we aimed to clarify the usefulness of B
      type natriuretic peptide (BNP) as a prognostic marker of cardiac function in SSA
      and in familial amyloidotic polyneuropathy (FAP). METHODS AND RESULTS: We studied
      13 patients with severe SSA and 14 patients with FAP. SSA patients, but not FAP
      patients, demonstrated a significant correlation of log BNP with the
      echocardiographic diastolic marker E/e' ratio (r = 0.78, p < 0.01). SSA patients
      also showed significant correlations between log BNP and log C-reactive protein
      or log high-sensitive troponin T (r = 0.70, p < 0.01; r = 0.64, p < 0.05). FAP
      patients, however, had significant correlations between log BNP and left
      ventricular wall thickness (intraventricular septum thickness diastole and
      posterior wall thickness diastole) (r = 0.73, p < 0.01; r = 0.77, p < 0.01). The
      mean log BNP level in the follow-up period was significantly higher than that in
      the diagnostic period in SSA patients (2.65 +/- 0.45 versus 2.36 +/- 0.40, p <
      0.01) but not in FAP patients (1.91 +/- 0.56 versus 1.93 +/- 0.45, p = 0.87). An
      especially notable phenomenon was the high plasma BNP level (>=180 pg/ml) in SSA
      patients. CONCLUSION: Plasma BNP levels may be a useful prognostic marker of
      cardiac function in SSA.

PMID- 24111637
TI  - Exciton energy transfer-based fluorescent sensing through aptamer-programmed self
      assembly of quantum dots.
AB  - A novel exciton energy transfer-based ultrasensitive fluorescent sensing strategy
      for the detection of biological small molecules and protein has been established
      through split aptamer-programmed self-assembly of quantum dots (QDs). The signal
      is produced from exciton energy transfer of the self-assembled QDs. The
      recognition is accomplished using an aptamer sensor scaffold designed with two
      split fragment sequences, which specifically bind to the model analytes. The
      extent of particle assembly, induced by the analyte-triggered self-assembly of
      QDs, leads to an exciton energy transfer effect between interparticles, giving a
      readily detectable fluorescent quenching and red shift of the emission peak,
      which enables us to quantitate the target in dual signal modes. The application
      of the technique is well demonstrated using two representative split aptamer
      based model systems for the detection of adenosine and thrombin. The sensitivity
      of this exciton energy transfer-based fluorescent sensing is much better than
      that of plasmonic coupling-based colorimetric methods. Limit of detections (LODs)
      down to 12 nM and 15 pM can be achieved for adenosine and thrombin, respectively.
      The sensing strategy is proposed as a general platform for robust and specific
      aptamer-target analysis which could be further developed to monitor a wide range
      of target analytes. The concept and methodology developed in this work shows a
      good promise in the study of molecular binding events in the biological and
      medical applications. 

PMID- 24111638
TI  - Analysis of FEV1 decline in relatively healthy heavy smokers: implications of
      expressing changes in FEV1 in relative terms.
AB  - Progressive decline in lung function has been widely accepted as the hallmark of
      chronic obstructive pulmonary disease (COPD); however, recent evidence indicates
      that the rate of decline measured as decline in forced expiratory volume in one
      second (FEV1) is higher in mild to moderate COPD than in severe COPD. Usually
      changes in FEV1 are measured in ml that is "absolute"; however, changes can also
      be measured "relative" as a percentage of the actual FEV1. We hypothesize that
      relative measurements could be more appropriate than absolute measurements for
      describing changes in lung function. We analyzed data from 3,218 relatively
      healthy heavy smokers who participated in the Danish Lung Cancer Screening Trial.
      The influences of age, sex, height, body mass index, smoking, and severity of
      airflow limitation on FEV1 were analyzed in mixed effects models. In absolute
      terms those with the best lung function consistently showed the steepest decline,
      whereas in relative terms most fast decliners are found among those with low lung
      function. Measuring changes in relative terms implied statistically significant
      acceleration of decline with advancing age, smoking (pack-years) and severity of
      airflow limitation. Relative measurements may lead to a better understanding of
      changes in lung function. Smoking and severity of airflow limitation speed up the
      loss of lung function, and this emphasizes the importance of abstaining from
      smoking the sooner the better. Measuring changes in relative terms could have
      important implications for the interpretation of results from clinical trials
      where FEV1 is the primary outcome. DLCST; www.ClinicalTrials.org , registration
      number: NCT00496977.

PMID- 24111641
TI  - Evolution of male coloration during a post-Pleistocene radiation of Bahamas
      mosquitofish (Gambusia hubbsi).
AB  - Sexual signal evolution can be complex because multiple factors influence the
      production, transmission, and reception of sexual signals, as well as receivers'
      responses to them. To grasp the relative importance of these factors in
      generating signal diversity, we must simultaneously investigate multiple
      selective agents and signaling traits within a natural system. We use the model
      system of the radiation of Bahamas mosquitofish (Gambusia hubbsi) inhabiting blue
      holes to test the effects of resource availability, male body size and other life
      history traits, key aspects of the transmission environment, sex ratio, and
      predation risk on variation in multiple male color traits. Consistent with
      previous work examining other traits in this system, several color traits have
      repeatedly diverged between predation regimes, exhibiting greater elaboration in
      the absence of predators. However, other factors proved influential as well, with
      variation in resource levels, body size, relative testes size, and background
      water color being especially important for several color traits. For one
      prominent signaling trait, orange dorsal fins, we further confirmed a genetic
      basis underlying population differences using a laboratory common-garden
      experiment. We illustrate a promising approach for gaining a detailed
      understanding of the many contributing factors in the evolution of multivariate
      sexual signals. 

PMID- 24111643
TI  - Breastfeeding: a holistic concept analysis.
AB  - Breastfeeding is a critical public health intervention. Nurses play a vital role
      in promoting and supporting optimal breastfeeding practices in infants and young
      children. An analysis following the eight-part Walker & Avant method provides
      clarity and context to the concept of breastfeeding. The antecedents of the
      concept of breastfeeding indicate nurse interventions to facilitate and the
      consequences provide key points for education related to the benefits of
      breastfeeding. 

PMID- 24111642
TI  - Enantioselective synthesis of 2-substitued-tetrahydroisoquinolin-1-yl glycine
      derivatives via oxidative cross-dehydrogenative coupling of tertiary amines and
      chiral nickel(II) glycinate.
AB  - The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycines was
      achieved by an oxidative cross-dehydrogenative coupling (CDC) reaction. This
      method for activation of the alpha-C-H bonds of amines with chiral nickel(II)
      glycinate using o-chloranil as the sole oxidant afforded highly
      diastereoselective coupling adducts. The decomposition of coupling adducts
      readily afforded 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives. 

PMID- 24111644
TI  - Description of the phenotypes of 63 heterozygous, homozygous and compound
      heterozygous patients carrying the Hb Groene Hart [alpha119(H2)Pro->Ser; HBA1:
      c.358C>T] variant.
AB  - We here report the phenotypes and genotypes of 63 patients of North African
      origin, carriers of Hb Groene Hart [Hb GH, alpha119(H2)Pro -> Ser; HBA1:
      c.358C>T], an alpha(+)-thalassemia (alpha(+)-thal) hemoglobin (Hb) variant. Fifty
      patients were heterozygous, five were homozygous and eight also carried the
      common -alpha(3.7) (rightward) deletion in compound heterozygosity. The
      expression of the alpha(GH)-globin chain is increased in the following order:
      heterozygous, compound heterozygous and homozygous. Parallel significant changes
      of mean corpuscular Hb (MCH) and mean corpuscular volume (MCV) were also
      observed. Our large cohort of Hb GH carriers could have been obtained by the
      systematic realization of globin chain separation by reversed phase liquid
      chromatography (RP-LC) in our routine Hb testing.

PMID- 24111645
TI  - Repeat treatment with icatibant for multiple hereditary angioedema attacks: FAST
      2 open-label study.
AB  - BACKGROUND: The For Angioedema Subcutaneous Treatment (FAST)-2, a phase III,
      double-blind, randomized, multicenter, placebo-controlled study
      (ClinicalTrials.gov identifier: NCT00500656), established the efficacy and safety
      of single injections of icatibant, a bradykinin B2 receptor antagonist, in the
      treatment of hereditary angioedema (HAE) attacks. Here, we evaluate the efficacy
      and safety of repeated treatment with icatibant in adult patients experiencing
      HAE attacks during the FAST-2 open-label extension (OLE) phase. METHODS: Patients
      completing the controlled phase were eligible to participate in the OLE phase and
      receive open-label icatibant (30 mg subcutaneously) for the treatment of
      cutaneous, abdominal, and/or laryngeal HAE attack(s) severe enough to warrant
      treatment. Time to onset of symptom relief was calculated for each attack.
      Descriptive analyses (median, 95% CIs) were performed for all attacks; post hoc
      analyses were conducted in patients with at least five icatibant-treated attacks
      throughout the FAST-2 OLE phase. Safety was also monitored. RESULTS: Fifty-four
      patients received icatibant for 374 attacks (176 cutaneous, 168 abdominal, and 30
      laryngeal). For cutaneous and/or abdominal attacks (attacks 2-5), the median
      times to onset of symptom relief ranged between 2.0 and 2.5 h. For all laryngeal
      attacks, the median times to regression (start of improvement) of symptoms ranged
      between 0.3 and 4.0 h. Post hoc analyses showed that the overall median time to
      onset of symptom relief was 2.0 h. Overall, 89.8% of attacks resolved with a
      single icatibant injection. No drug-related serious adverse events were reported.
      CONCLUSIONS: These findings have demonstrated the efficacy and safety of repeated
      icatibant treatment for HAE attacks.

PMID- 24111646
TI  - Nano-anchors with single protein capacity produced with STED lithography.
AB  - Acrylate nanoanchors of subdiffraction-limited diameter are written with optical
      stimulated emission depletion (STED) lithography. After incubation, 98% of all
      nanoanchors are loaded quickly with fluorescently labeled antibodies. Controlling
      the size of the nanoanchors allows for limiting the number of the antibodies.
      Direct stochastic optical reconstruction microscopy (dSTORM) imaging, statistical
      distribution of fluorescence, quantitative fluorescence readout, and single
      molecule blinking consistently prove that 80% of the nanoanchors with a 65 nm
      diameter are carrying only one antibody each, which are functional as confirmed
      with live erythrocytes. 

PMID- 24111647
TI  - Fibre type-specific satellite cell content in two models of muscle disease.
AB  - AIMS: Muscle satellite cells (SCs) are responsible for the regenerative events
      following muscle fibre injury. This study aimed to improve our understanding of
      SC behaviour in two models of muscle disorder with different pathological
      mechanisms and onset of disease. METHODS AND RESULTS: Pax7(+) SC content was
      assessed in types I and II fibres of patients with Duchenne muscular dystrophy
      (DMD; n = 9; age 13 +/- 2 years), polymyositis/dermatomyositis (PM/DM; n = 9; age
      52 +/- 12 years) and in controls (n = 5; age 26 +/- 5 years). Pax7(+) SCs number
      in type I and II fibres was higher (P < 0.05) in DMD and in PM/DM compared to
      controls. Type I fibres were associated with a higher number of Pax7(+) SCs
      compared to type II fibres only in DMD; Pax7(+) SCs number in type I fibres was
      about threefold higher in DMD compared to PM/DM (P < 0.05). In DMD, Pax7(+) SC
      content in small regenerating fibres (0.09 +/- 0.09 SCs/fibre) was similar to
      that in fibres from healthy skeletal muscle. The proportion of activated SCs (Ki
      67(+) SCs) was fivefold lower in DMD (0.4 +/- 0.4%) compared to PM/DM (2.8 +/-
      2%). Pax7(+) cells located outside the basal lamina were observed in DMD muscles
      only. CONCLUSION: The capacity to generate new SCs is increased even in severely
      impaired muscles and a fibre type-specific enhancement of SC occurs in type I
      muscle fibres in DMD.

PMID- 24111648
TI  - Pneumococcal antibodies in kidney transplant recipients are predictive of patient
      survival.

PMID- 24111649
TI  - Evaluation of safety and efficacy of purgative manna (billinaster drop) and
      glycerin suppository in icterus of healthy term newborns.
AB  - OBJECTIVE: The aim of the present study was to investigate safety and efficacy of
      billinaster drop and glycerin suppository in hyperbilirubinemia of healthy term
      newborns who had passage of first meconium. METHODS: In a randomized clinical
      trial, 90 neonates with total plasma bilirubin(TPB) level of 15-20mg/dL, were
      randomly assigned to be treated with alone phototherapy (control) or 5drop/kg of
      bilinaster drop every eight hours and phototherapy(B) or half of glycerin
      suppository every twelve hours and phototherapy(G). The primary outcomes were
      safety of drugs and efficacy in obtaining TPB of less than 14 mg/dL as measured
      at the beginning, 12, 24 and 48 hours after intervention. Secondary endpoint was
      hospitalization days. RESULTS: After 48 hours of intervention, achieving TPB of
      less than 14 mg/dL was seen in 50 %( N=15) in control group, 73.3 %( N=22) in B
      group and 86.7 %( N=26 neonates) in G group (P= 0.01). Watery stool was seen in
      two neonates of glycerin group and safety of the treatments was not significantly
      different. Mean of TPB 12 hours after beginning of phototherapy(mean+/-SD:14.38+/
      2.27mg/dL in G, 15.97+/-1.96mg/dL in B and 16.67+/-1.77mg/dL in control), 24
      hours after intervention(mean+/-SD:12.56 +/-1.59mg/dL in G, 12.57+/-2.05mg/dL in
      B and 14.36+/-2.26mg/dL in control), 48 hours after intervention (mean+/-SD: 9.34
      +/- 1.6mg/dL in G, 9.96 +/- 2.95mg/dL in B and 12.27 +/- 2.4mg/dL in control) and
      mean of hospitalization days (mean+/- SD: 1.5 +/- 0.4days in G, 1.7 +/- 0.4days
      in B and 2.9 +/- 1.1days in control) were significantly lower in glycerin and
      billinaster groups. CONCLUSION: Bilinaster drop and glycerin suppository can be
      used as hazardless, efficient and cost effective drugs in treatment of neonatal
      hyperbilirubinemia.

PMID- 24111651
TI  - Wetting behaviour of silicone- and resin-based root canal sealers.
AB  - AIM: To evaluate the wetting behaviour of three different classes of endodontic
      sealers, silicone (Roekoseal Automix)-, epoxy-resin (2Seal, AH Plus)- and
      methacrylate-based sealers (EndoRez, RealSeal, RealSeal SE, Seal 3D) on dentine
      specimens with and without chemical pre-treatment. METHODOLOGY: Eighty caries
      free molar teeth were used for the preparation of 160 dentine discs. Half of the
      discs were rinsed with distilled water, and the remainder were treated with 3%
      NaOCl, followed by 17% EDTA and 2% CHX to simulate the final rinse under clinical
      like conditions. For both irrigation methods, 10 droplets of each sealer were
      analysed. Data were statistically analysed using multivariate anova (general
      linear model, alpha = 0.05) that assessed the effects of material, irrigation
      procedure and time on the measured contact angle as well as their interaction.
      RESULTS: Contact angle was primarily influenced by the material (P < 0.05),
      followed by time (P < 0.05). Irrigation procedure had a significant influence (P
      < 0.05) on contact angle formation of all materials except EndoRez and AH Plus.
      EndoRez had the highest values, and Roekoseal Automix had the lowest values for
      all measurements. RealSeal SE had lower values after chemical treatment.
      CONCLUSIONS: The silicone-based sealer Roekoseal Automix had better wettability
      than epoxy-resin- or methacrylate-based sealers. The irrigation regime
      significantly favoured the wettability of 2Seal and RealSeal SE.

PMID- 24111650
TI  - Family income in early childhood and subsequent attention deficit/hyperactivity
      disorder: a quasi-experimental study.
AB  - BACKGROUND: Studies have found negative associations between socioeconomic
      position and attention deficit/hyperactivity disorder (ADHD), but it remains
      unclear if this association is causal. The aim of this study was to determine the
      extent to which the association between family income in early childhood and
      subsequent ADHD depends on measured and unmeasured selection factors. METHODS: A
      total of 811,803 individuals born in Sweden between 1992 and 2000 were included
      in this nationwide population-based cohort study. Diagnosis of ADHD was assessed
      via the Swedish national Patient Register and the Swedish Prescribed Drug
      Register. Annual family income during offspring's first 5 years in life was
      collected prospectively from the Swedish Integrated Database for Labour Market
      Research and divided into quartiles by (lower) family disposable income. We
      predicted ADHD from family income while controlling for covariates and also
      comparing differently exposed cousins and siblings to control for unmeasured
      familial confounding. RESULTS: The crude analyses suggested that children exposed
      to lower income levels were at increased risk for ADHD (HRQ uartile1  = 2.52; 95%
      CI, 2.42-2.63; HRQ uartile2  = 1.52; 95% CI, 1.45-1.58; HRQ uartile3  = 1.20; 95%
      CI, 1.14-1.15). This dose-dependent association decreased after adjustment for
      measured covariates (HRQ uartile1  = 2.09; 95% CI, 2.00-2.19; HRQ uartile2  =
      1.36; 95% CI, 1.30-1.42; HRQ uartile3  = 1.13; 95% CI, 1.08-1.18). Although the
      association was attenuated in cousin comparisons (HRQ uartile1  = 1.61; 95% CI,
      1.40-1.84; HRQ uartile2  = 1.28; 95% CI, 1.12-1.45; HRQ uartile3  = 1.14; 95% CI,
      1.01-1.28) and sibling comparison models (HRQ uartile1  = 1.37; 95% CI, 1.07
      1.75; HRQ uartile2  = 1.37; 95% CI, 1.12-1.68; HRQ uartile3  = 1.23; 95% CI, 1.04
      1.45), it remained statistically significant across all levels of decreased
      disposable family income. CONCLUSIONS: Our results indicated that low family
      income in early childhood was associated with increased likelihood of ADHD. The
      link remained even after controlling for unmeasured selection factors,
      highlighting family income in early childhood as a marker of causal factors for
      ADHD.

PMID- 24111652
TI  - Hydrogen-oxidizing hydrogenases 1 and 2 of Escherichia coli regulate the onset of
      hydrogen evolution and ATPase activity, respectively, during glucose fermentation
      at alkaline pH.
AB  - Simultaneous measurement of redox potential (Eh ) and determination of H2
      evolution kinetics using a pair of titanium silicate and platinum redox
      electrodes in fermenting cultures of Escherichia coli wild type and different
      mutants lacking hydrogenases 1 (Hyd-1) or 2 (Hyd-2) revealed that Hyd-1 controls
      the onset of H2 evolution at slightly alkaline pH (pH 7.5) and under oxidizing Eh
      . In addition, Hyd-2 influences the N,N'-dicyclohexylcarbodiimide-inhibited
      ATPase activity in fermenting cells and thus regulates the proton F0 F1 -ATPase
      at the alkaline pH but under reducing Eh . 

PMID- 24111653
TI  - Chlorhexidine droplet splash from a skin preparation gallipot: effect of height
      of pouring.
AB  - Chlorhexidine contamination of equipment used in central neuraxial anaesthesia
      has been implicated in causing adhesive arachnoiditis. We measured the extent of
      chlorhexidine splash during pouring into a gallipot (antiseptic skin preparation
      container) from heights of 5 cm, 10 cm, 15 cm and 20 cm. Twenty experiments were
      performed at each height. Measurements made up to a horizontal distance of 40 cm
      radius from the gallipot showed a median (IQR [range]) maximum spread of splash
      droplets >= 2 mm diameter of 26.2 (10.2-36.4 [0-40]) cm. The 40-cm radius
      measurement area was divided into 5-cm-wide zones to assess spread. At pouring
      heights of 15 cm and 20 cm, all zones were contaminated. These results
      demonstrate that pouring chlorhexidine into a gallipot generates significant
      splash, and we recommend that this should be avoided near equipment used for
      neuraxial anaesthesia.

PMID- 24111654
TI  - Polyhydramnios and adverse perinatal outcome - what is the actual cutoff?
AB  - OBJECTIVE: The purpose of this study was to evaluate the association between
      amniotic fluid index (AFI) and adverse perinatal outcome, and whether a critical
      cutoff can be defined. METHODS: A retrospective cohort study was conducted.
      Included were patients who were admitted to the ultrasound unit of the tertiary
      medical center between the years 1988 and 2010. Parturients were classified into
      five groups according to their AFI: <20 (n = 9974; comparison group), 20-23 (n =
      2771), 24-27 (n = 1315), 28-31 (n = 494) and 32 + (n = 260). Pregnancy and the
      perinatal outcomes were compared between the groups. Statistical analysis
      included the chi-square tests for trends, and multivariable models to control for
      confounders (with AFI as a dummy variable). RESULTS: A significant linear
      association was found between AFI and adverse perinatal outcomes including
      hypertensive disorders, diabetes mellitus, preterm labor, macrosomia, placental
      abruption and low birth weight. Furthermore, using multivariable logistic
      regression models, controlling for confounders such as maternal and gestational
      age, hypertension, diabetes mellitus, etc., the significant association between
      all four subgroups of AFI > 20 and adverse perinatal outcomes remained.
      CONCLUSION: A significant linear association exists between AFI > 20 and
      perinatal complications such as perinatal mortality, low Apgar scores and preterm
      labor. Hence, the critical cutoff for polyhydramnios should be re-evaluated.

PMID- 24111655
TI  - Autobiographical memory bias in social anxiety.
AB  - In social anxiety the psychological self is closely related to the feared
      stimulus. Socially anxious individuals are, by definition, concerned about how
      the self is perceived and evaluated by others. As autobiographical memory is
      strongly related to views of the self it follows that biases in autobiographical
      memory play an important role in social anxiety. In the present study high (n =
      19) and low (n = 29) socially anxious individuals were compared on
      autobiographical memory bias, current goals, and self-discrepancy. Individuals
      high in social anxiety showed a bias towards recalling more negative and more
      social anxiety-related autobiographical memories, reported more current goals
      related to overcoming social anxiety, and showed larger self-discrepancies. The
      pattern of results is largely in line with earlier research in individuals with
      PTSD and complicated grief. This suggests that the relation between
      autobiographical memory bias and the self is a potentially valuable trans
      diagnostic factor. 

PMID- 24111657
TI  - Functional variation of the transthyretin gene among human populations and its
      correlation with amyloidosis phenotypes.
AB  - INTRODUCTION: Heterogeneity in the genotype-phenotype correlation of
      transthyretin (TTR)-related amyloidosis has been reported, suggesting that other
      factors may interact with disease-causing mutations. Additional genetic variants
      in the TTR gene and its surrounding regions may influence disease phenotype. To
      explore this hypothesis, we analyzed the TTR variation among human populations to
      identify functional inter-ethnic differences that could influence the TTR-related
      amyloidosis. METHODS: Using the 1000 Genomes Project database, we analyzed a 20
      kb region in 1092 apparently healthy individuals who belonged to 14 human
      populations. In silico analyses were performed to determine the functional impact
      of genetic variants. RESULTS: These analyses showed that significant ethnic
      differences are present in the TTR gene, and some differences may affect TTR gene
      function. Specifically, the non-coding variants potentially associated with
      regulatory function showed a significant diversity between African and non
      African individuals. DISCUSSION AND CONCLUSIONS: Our results highlighted that cis
      regulatory variants may contribute to the cardiac TTR-related amyloidosis
      observed in patients carrier of Val122Ile mutation, the most common in population
      with African origin. Indeed, non-coding variants differentiated in Africans are,
      in some cases, located in binding sites of transcription factors involved in
      cardiac development and function (i.e. E2F3_2, REST, and TEAD).

PMID- 24111658
TI  - Mental health among people with psoriasis undergoing patient education in climate
      therapy.
AB  - This study investigated the mental health of people with psoriasis undergoing
      patient education in climate therapy. A prospective design included a baseline
      assessment and two follow-ups after a 3-week patient education program.
      Participants were 254 adults. Positive mental health was measured by the mental
      health continuum short form (0-70), and negative mental health by the emotional
      distress subscale (1-4) of the health education impact questionnaire. Paired
      samples t-tests were used to evaluate changes in mental health from baseline to
      follow-up. Multiple linear regression was used to analyse the ability of socio
      demographic and clinical variables and emotional distress to predict changes in
      positive mental health. To predict change in negative mental health we repeated
      the same analysis but with a change in negative mental health as a dependent
      variable and positive mental health as an independent variable. The results show
      that positive mental health and health-related emotional distress improved
      significantly from before to after the intervention by 7.1 points, p < 0.001 and
      0.21 points, p < 0.001) respectively. At the second follow-up, health-related
      emotional distress remained significantly improved compared with baseline levels
      by 0.11 points, p = 0.004. The longer participants had lived with psoriasis (
      beta = 146, p = 0.027), and the presence of co-morbid health problems (beta  = 
      111, p = 0.051) the greater the improvement in the positive mental health
      immediately after the intervention. No predictors were identified for negative
      mental health. This study indicates that the promotion of positive mental health
      needs to be integrated into the climate therapy program, and sustained in their
      home context. 

PMID- 24111660
TI  - Water-ionomer interfacial interactions investigated by infrared spectroscopy and
      computational methods.
AB  - Structures for interfacial water condensed in pores and channels of the
      fluorinated ionomer Nafion from low relative humidity atmosphere were probed
      through the use of Fourier transform infrared (FTIR) spectroscopy and support
      from classical and quantum chemical calculations. Modern FTIR spectra of H2O and
      the O-H stretching region for the deuterium-substituted HOD species interacting
      at the water-ionomer interface in Nafion exchanged by sodium cations are reported
      and compared to characteristics observed in the earlier studies that employed a
      dispersive infrared spectrometer and unspecified spectral resolution. Molecular
      simulations that examine the orientations of water molecules in the vicinity of
      ionomer were applied to understand the appearance of multiple free O-H stretching
      bands and the effect of HOD addition. One computational approach was based on a
      classical force field model, and the other employed density functional theory
      (DFT) to investigate atomic-scale interactions of water with regions of different
      hydrophobicity and charge on a perfluorosulfonate ionomer segment. The results
      suggest hydrogen bonding stabilizes the types of water-ionomer environments that
      can lead to multiple free O-H stretching vibrational features in experimental
      spectra. The studies shed light on the structure of H2O at interfaces inside ion
      conducting membrane materials and have potential for application in elucidating
      structure at different types of water interfaces. 

PMID- 24111659
TI  - Sortase-tag expressed protein ligation: combining protein purification and site
      specific bioconjugation into a single step.
AB  - Efficient labeling of protein-based targeting ligands with various cargos (drugs,
      imaging agents, nanoparticles, etc.) is essential to the fields of molecular
      imaging and targeted therapeutics. Many common bioconjugation techniques,
      however, are inefficient, nonstoichiometric, not site-specific, and/or
      incompatible with certain classes of protein scaffolds. Additionally, these
      techniques can result in a mixture of conjugated and unconjugated products, which
      are often difficult to separate. In this study, a bacterial sortase enzyme was
      utilized to condense targeting ligand purification and site-specific conjugation
      at the C-terminus into a single step. A model was produced to determine optimal
      reaction conditions for high conjugate purity and efficient utilization of cargo.
      As proof-of-principle, the sortase-tag expressed protein ligation (STEPL)
      technique was used to generate tumor-specific affinity ligands with fluorescent
      labels and/or azide modifications at high purity (>95%) such that it was not
      necessary to remove unconjugated impurities. Click chemistry was then used for
      the highly efficient and site-specific attachment of the azide-modified targeting
      ligands onto nanoparticles. 

PMID- 24111661
TI  - Stability and purity of a bacteriophage cocktail preparation for nebulizer
      delivery.
AB  - The aim of this study was to determine the stability and purity of a phage
      cocktail to be delivered by nebulization. A cocktail of three phages active
      against Pseudomonas aeruginosa isolates from cystic fibrosis patients was
      developed for a potential nebulized formulation. The individual phages were
      examined for their retention of activity over time, while the phage cocktail was
      analysed for bacterial contaminant and endotoxin level according to regulatory
      requirements for nebulized products. The phage cocktail was nebulized using a
      Porta-neb nebulizer connected to an Anderson cascade impactor. The three phages
      retained activity over a period of 180 days storage at room temperature and at 4
      degrees C. Nebulized phages were recovered in the lower stages of the cascade
      impactor indicative of potential delivery deep into the lungs. The phage cocktail
      met bacterial limits but the endotoxin levels measured with the Limulus
      amoebocyte lysate (LAL) test remained considerably in excess of acceptable levels
      even following purification. These findings suggest that nebulization of phage is
      a viable delivery option; although, there is a need for appropriate
      depyrogenation strategies to remove bacterial endotoxins from phage-based
      preparations to meet regulatory requirements. SIGNIFICANCE AND IMPACT OF THE
      STUDY: With increasing reports of bacterial resistance to antibiotics and the
      lack of new antibiotics being produced, bacteriophage therapy is becoming an
      attractive alternative. There has been no published report on the quality
      assurance of bacteriophage product to date. This is the first study on the
      quality assurance of a Pseudomonas aeruginosa phage cocktail following
      pharmacopoeial requirements. The presence of bacterial endotoxin was found to be
      the key stumbling block for meeting regulatory criteria.

PMID- 24111662
TI  - Medical utilization and cost in patients with overlap syndrome of chronic
      obstructive pulmonary disease and asthma.
AB  - BACKGROUND: Little information is available regarding medical utilization and
      cost in patients with overlap syndrome of chronic obstructive pulmonary disease
      (COPD) and asthma. The purpose of this study is to analyze medical utilization
      and cost in patients with overlap syndrome and to compare them to COPD patients
      without asthma. METHODS: Using the 2009 Korean National Health Insurance (NHI)
      database, COPD patients were identified. Medical utilization and costs were also
      analyzed. RESULTS: Of a total of 185,147 patients identified with COPD, 101,004
      patients were classified with overlap syndrome of COPD and asthma and 84,143
      patients with COPD without asthma. In 2009, the percentages of emergency room
      visits, admissions, and intensive care unit admissions were 14.6%, 30.5%, and
      0.5%, respectively, in the patients with overlap syndrome group and 5.0%, 14.1%,
      and 0.2%, respectively, in the COPD patients without asthma group (p < 0.05 for
      all comparisons). The cost of medical utilization was 790 +/- 71 US dollars per
      person and 3,373 +/- 4,628 dollars per person for outpatient and inpatient
      services, respectively, in the patients with overlap syndrome and 413 +/- 512 and
      3,010 +/- 5,013, respectively, in the COPD patients without asthma (p < 0.05 for
      all comparisons). Multiple linear regression showed that age, sex, overlap
      syndrome, hospitalization in the last year, low socioeconomic status, and type of
      hospital use were significant factors affecting medical utilization and cost.
      CONCLUSIONS: In patients with overlap syndrome, both medical utilization and cost
      were higher than in COPD patients without asthma.

PMID- 24111663
TI  - Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated
      rats.
AB  - Lung injury is the main cause of death in acute paraquat (PQ) intoxication.
      Sivelestat (SV), a neutrophil elastase inhibitor, is effective in reducing
      inflammation in acute lung injury. The aim of this study was to examine the
      effect of SV on acute lung injury in PQ-intoxicated rats. Seven-week-old male
      Sprague-Dawley rats were randomly assigned to four groups: (1) control group
      (group N; n = 5); (2) PQ + normal saline (group P; n = 6); (3) normal saline + SV
      (group S; n = 6) and (4) PQ + SV (group PS; n = 6). SV treatment
      (intraperitoneally [i.p.], 20 mg/kg) was performed 30 minutes after PQ injection
      (i.p., 100 mg/kg), and injections were continued every hour for a total of five
      doses. One hour after the last treatment, blood samples were obtained for
      analysis of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha). Lung
      sections were stained with hematoxylin--eosin for light microscopic analysis.
      Neutrophil infiltration score of group PS was significantly lower than that of
      group P (p < 0.05). But, other scores and total score had no significant
      differences. IL-6 of group PS did not differ, compared to group P. In addition,
      there were no differences among the four groups. TNF-alpha of group PS was
      reduced, in comparison to the level of group P. SV attenuated neutrophil
      infiltration in PQ-induced acute lung injury in rats. In addition, systemic
      inflammation was partially suppressed with SV treatment, suppressing TNF-alpha
      production. These results suggest that SV reduces paraquat-induced lung injury,
      at least partially, by inhibiting neutrophil infiltration and TNF-alpha
      secretion.

PMID- 24111664
TI  - Toll-like receptor 9-independent responsiveness of human monocytes to microbial
      DNA.

PMID- 24111665
TI  - The influence of sampling design on species tree inference: a new relationship
      for the New World chickadees (Aves: Poecile).
AB  - In this study, we explore the long-standing issue of how many loci are needed to
      infer accurate phylogenetic relationships, and whether loci with particular
      attributes (e.g., parsimony informativeness, variability, gene tree resolution)
      outperform others. To do so, we use an empirical data set consisting of the seven
      species of chickadees (Aves: Paridae), an analytically tractable, recently
      diverged group, and well-studied ecologically but lacking a nuclear phylogeny. We
      estimate relationships using 40 nuclear loci and mitochondrial DNA using four
      coalescent-based species tree inference methods (BEST, *BEAST, STEM, STELLS).
      Collectively, our analyses contrast with previous studies and support a sister
      relationship between the Black-capped and Carolina Chickadee, two superficially
      similar species that hybridize along a long zone of contact. Gene flow is a
      potential source of conflict between nuclear and mitochondrial gene trees, yet we
      find a significant, albeit low, signal of gene flow. Our results suggest that
      relatively few loci with high information content may be sufficient for
      estimating an accurate species tree, but that substantially more loci are
      necessary for accurate parameter estimation. We provide an empirical reference
      point for researchers designing sampling protocols with the purpose of inferring
      phylogenies and population parameters of closely related taxa. 

PMID- 24111668
TI  - Combined treatment with the antibiotics kanamycin and streptomycin promotes the
      conjugation of Escherichia coli.
AB  - It is widely accepted that antibiotics provide a critical selective pressure for
      the horizontal transfer of antibiotic resistance between bacterial species. This
      study demonstrated that a combination of low doses of kanamycin and streptomycin,
      which inhibited the growth of recipient and donor cells, respectively, had
      positive effects on the transmission of the conjugation plasmids pRK2013,
      pSU2007, and RP4 from Escherichia coli DH5alpha to HB101 at their minimum
      inhibitory concentrations (MICs). Administration of either antibiotic alone as
      well as other antibiotics in combination or alone did not have this effect. Two
      dimensional electrophoresis revealed that 60 proteins were downregulated and 14
      proteins were upregulated in the conjugation of E. coli DH5alpha (pRK2013) and
      HB101 in the presence of kanamycin and streptomycin. Of these proteins, 64 were
      subsequently identified by mass spectrometry. Two antibiotic-induced genes
      encoding oligopeptide-binding protein (OppA) and ribose-binding protein (RbsB)
      were further confirmed by quantitative real-time PCR. When these genes were
      deleted, the number of transconjugants decreased in the same fashion as when the
      cells were treated with kanamycin and streptomycin. These results indicate that
      the process of E. coli conjugation may be promoted by combination treatment with
      kanamycin and streptomycin and that two proteins potentially participated in this
      process.

PMID- 24111669
TI  - Chronic myeloproliferative neoplasms and risk of osteoporotic fractures; a
      nationwide population-based cohort study.
AB  - Patients with systemic mastocytosis have an increased risk of osteoporosis,
      however, the risk of osteoporotic fractures among the classic chronic
      myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET),
      polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We
      conducted a population-based cohort study to determine the risk of osteoporotic
      fractures among three cohorts of patients with newly diagnosed ET, PV, and CML.
      Patients were identified in medical registers including all Danish hospitals
      during 1980-2010 and were followed until first osteoporotic fracture. Fracture
      risk was compared to cohorts from the general population matched on age, sex and
      calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort
      members. We found that the risk of femoral fracture after 5 years was
      consistently higher than the general population, being 3.01% (95% confidence
      interval (CI): 2.20-4.10), 4.74% (95%CI: 4.06-5.52) and 4.64% (95%CI: 3.29-6.53)
      among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral
      fracture was increased 1.19-fold (95% CI: 0.94-1.51) for ET patients, 1.82-fold
      (95% CI: 1.62-2.04) for PV patients, and 2.67-fold (95% CI: 1.97-3.62) for CML
      patients. We conclude that CMPN patients are at higher risk of osteoporotic
      fractures than the general population. 

PMID- 24111670
TI  - Virus-inactivated plasma and intraventricular hemorrhage in preterm neonates.

PMID- 24111671
TI  - Apical extrusion of bacteria when using reciprocating single-file and rotary
      multifile instrumentation systems.
AB  - AIM: To evaluate ex vivo, apical bacterial extrusion associated with two
      reciprocating single-file systems (WaveOne and Reciproc) compared with a
      conventional multifile rotary system (BioRace). METHODOLOGY: Forty-five human
      single-rooted mandibular incisors were used. Endodontic access cavities were
      prepared, and root canals were contaminated with an Enterococcus faecalis
      suspension. Following incubation at 37  degrees C for thirty days, the
      contaminated teeth were divided into three groups of 15 specimens each (G1 -
      Reciproc, G2 - WaveOne and G3 - BioRace). Positive and negative controls
      consisted of 5 infected teeth and 3 uninfected incisors that were instrumented
      with one of the tested NiTi systems, respectively. Bacteria extruded from the
      apical foramen during instrumentation were collected into vials containing 0.9%
      NaCl. The microbiological samples were taken from the vials and incubated in
      brain heart agar medium for 24 h. The resulting bacterial titre, in colony
      forming units (CFU) per mL, was determined, and these data were analysed by
      Wilcoxon matched-pairs signed rank test and Kruskal-Wallis H-test. The level of
      significance was set at alpha = 0.05. RESULTS: No significant difference was
      found in the number of CFU between the two reciprocating systems (P = 0.41). The
      conventional multifile rotary system group was associated with significantly
      higher CFU than both of the two reciprocating groups (P = 0.01). CONCLUSIONS: All
      instrumentation systems extruded bacteria beyond the foramen. However, both
      reciprocating single-file systems extruded fewer bacteria apically than the
      conventional multifile rotary system.

PMID- 24111672
TI  - Life-history traits and population decline of the Atlantic mackerel Scomber
      scombrusin the Adriatic Sea.
AB  - This study investigated demographic structure and reproductive characteristics of
      the Atlantic mackerel Scomber scombrus, in relation to landing trends in the
      northern-central Adriatic Sea. Results highlighted the occurrence of only small
      sized and young-age individuals, and a marked decline from the 1990s to the
      present in maximum age (from 8 to 3 years) and total length (L(T); from 420 to
      360 mm). Fecundity ranged between 40,000 and 190,000 eggs, and was related to
      female L(T). High levels of atresia implied lower values of actual fecundity.
      Sexual maturity was attained by 72.8% of individuals in their first year of life
      at 200 mm. The reduction in maximum L(T) resulted in a marked decline in the
      population egg production, while the reduction in maximum age implied that
      females participated in fewer spawning events.

PMID- 24111673
TI  - Thermo-induced shape-memory PEG-PCL copolymer as a dual-drug-eluting
      biodegradable stent.
AB  - In this work, a thermo-induced shape-memory drug-eluting stent (SMDES) has been
      developed by cross-linking PEG-PCL copolymer (cPEG-PCL). The stent is able to
      perform the shape-memory effect from a temporary linear form to a permanent
      spiral shape with the transition temperature close to body temperature. The stent
      incorporates a controlled dual drug-release system for the purpose of preventing
      in-stent restenosis of the vessel for short- and long-term therapeutic effects.
      From the results, (1)H NMR and GPC indicate that the compositions of PEG-PCL
      block copolymers are similar to the feed ratios of PEG/epsilon-CL. A Young's
      modulus of the cPEG-PCL stent can be achieved that ranges from tens to one
      hundred megapascals by modulation of the mixing ratio of PEG/PCL. The cPEG-PCL
      stent is demonstrated to recover to its permanent shape with a high fixing ratio
      (>99%), recovery ratio (>90%), and recovery time (<10 s). DSC data reveals that
      the transition temperature is around body temperature (40  degrees C).
      Cytotoxicity tests prove that the cPEG-PCL_6040 stent has good biocompatibility.
      In vitro degradation tests show that the cPEG-PCL_6040 stent undergoes a bulk
      degradation of 47% after 60 days of incubation under flow conditions. Platelet
      adhesion and smooth muscle cell proliferation were significantly inhibited by
      coculture with a mitomycin C/curcumin-eluting stent as a result of the release of
      curcumin for antiplatelet adhesion during the initial 2 weeks followed by long
      term inhibition of smooth muscle cell hyperproliferation for 60 days via
      mitomycin C. After 60 days of incubation in a bioreactor, the appearance of the
      stent remains intact and shows no signs of recoiling or collapse. 

PMID- 24111675
TI  - Comment on B-type natriuretic Peptide predicts left atrial appendage thrombus in
      patients with nonvalvular atrial fibrillation.

PMID- 24111676
TI  - Reply: To PMID 23496263.

PMID- 24111679
TI  - Engineering spatial gradients of signaling proteins using magnetic nanoparticles.
AB  - Intracellular biochemical reactions are often localized in space and time,
      inducing gradients of enzymatic activity that may play decisive roles in
      determining cell's fate and functions. However, the techniques available to
      examine such enzymatic gradients of activity remain limited. Here, we propose a
      new method to engineer a spatial gradient of signaling protein concentration
      within Xenopus egg extracts using superparamagnetic nanoparticles. We show that,
      upon the application of a magnetic field, a concentration gradient of
      nanoparticles with a tunable length extension is established within confined egg
      extracts. We then conjugate the nanoparticles to RanGTP, a small G-protein
      controlling microtubule assembly. We found that the generation of an artificial
      gradient of Ran-nanoparticles modifies the spatial positioning of microtubule
      assemblies. Furthermore, the spatial control of the level of Ran concentration
      allows us to correlate the local fold increase in Ran-nanoparticle concentration
      with the spatial positioning of the microtubule-asters. Our assay provides a
      bottom-up approach to examine the minimum ingredients generating polarization and
      symmetry breaking within cells. More generally, these results show how magnetic
      nanoparticles and magnetogenetic tools can be used to control the spatiotemporal
      dynamics of signaling pathways. 

PMID- 24111680
TI  - Case series evidence for improvement of executive functions after late
      cranioplasty.
AB  - OBJECTIVE: Craniectomy, used to relieve refractory intracranial pressure in
      traumatic brain injury (TBI), may cause cognitive deficits which could be
      improved by skull breach repair. This paper studied whether late cranioplasty
      improves a specific pattern of cognitive functions. DESIGN: A case series of five
      TBI patients with craniectomy undergoing late cranioplasty (median interval time:
      14 months, range: 12-36). METHODS: Longitudinal neuropsychological and brain MRI
      assessments 1 week before cranioplasty and 3 months later. RESULTS: After
      cranioplasty, mean score of the verbal fluency test improved compared to pre
      cranioplasty (p = 0.02). Similarly, significant improvements after cranioplasty
      were observed in other tests scores exploring executive functions, such as
      working memory (p = 0.03) and speed of attention (p = 0.04), independently from
      the size and site of cranioplasty. CONCLUSIONS: The cognitive improvement induced
      by cranioplasty, even when performed after a long interval from craniectomy, may
      be due to the restoration of physiological cerebrospinal fluid circulation which,
      in turn, allows an efficient brain volume transmission signal circulation. The
      restoration of this essential way of signal communication seems to affect large
      scale neuronal networks responsible for the executive functions.

PMID- 24111681
TI  - "Replica-extraction-transfer" nanostructure-initiator mass spectrometry imaging
      of acoustically printed bacteria.
AB  - Traditionally, microbes are studied under controlled laboratory conditions as
      isolates in planktonic culture. However, this is a vast extrapolation from their
      natural state; development of new techniques is required to decipher the largely
      unknown world of microbial chemical interactions in more realistic environments.
      The field of mass spectrometry imaging has made significant progress in
      localizing metabolites in and around bacterial colonies, primarily by using MALDI
      and ESI-based techniques that interrogate the top surface of the sample.
      Unfortunately, surface-based laser-desorption techniques, such as nanostructure
      initiator mass spectrometry (NIMS), which has advantages in detection of small
      metabolite compounds and low background, has not been suitable for direct microbe
      imaging because desorption/ionization occurs on the bottom of the sample. Here,
      we describe a "replica-extraction-transfer" (REX) technique that overcomes this
      barrier by transferring biomolecules from agar cultures of spatially arrayed
      bacterial colonies onto NIMS surfaces; further, we demonstrate that acoustic
      printing of bacteria can be used to create complex colony geometries to probe
      microbial interactions with NIMS imaging. REX uses a solvent-laden semisolid
      (e.g., gel) to first extract metabolites from a microbial sample, such as a
      biofilm or agar culture; the metabolites are then replica "stamped" onto the NIMS
      surface. Using analytical standards we show that REX-NIMS effectively transfers
      and detects a range of small molecule compounds including amino acids and
      polyamines. This approach is then used to analyze the metabolite composition of
      streaked Shewanella oneidensis MR1 and Pseudomonas stutzeri RCH2 colonies and
      further resolve complex patterns produced by acoustic printing of liquid
      microbial cultures. Applying multivariate statistical analysis of the NIMS
      imaging data identified ions that were localized to different regions between and
      within colonies, as well as to the agar gel. Subsequent high-resolution tandem
      mass spectrometry was used to characterize two species-specific lipids that
      correlated with the spatial location of each microbial species and were found to
      be highly abundant in cell extracts. Overall, the use of acoustic printing of
      bacteria with REX-NIMS imaging will extend the range of analytical capabilities
      available for characterization of microbial interactions with mass spectrometry. 

PMID- 24111682
TI  - Perceptions of adolescent bullying: attributions of blame and responsibility in
      cases of cyber-bullying.
AB  - Cyber-bullying (where victims are targeted via online social networking or other
      electronic means) has gained increased attention in research and the broadcast
      media, but previous research has not investigated attribution of blame in such
      cyber-bullying events. This experiment hypothesized that participants would
      assign higher ratings of blame to bullying perpetrators when the bullying
      situations were depicted as having highly foreseeable outcomes (vs. unforeseeable
      outcomes), and as occurring in school (vs. online). In addition, a significant
      interaction was predicted between outcome foreseeability and bullying situation,
      with highly foreseeable in-school events being rated as the most predictable and
      attributable to the bully's actions. One-hundred sixty-three participants
      completed surveys containing demographic items, items regarding their past
      experiences of victimization, and one of four randomly-assigned vignettes
      detailing a bullying situation (which participants rated). While hypotheses
      regarding outcome foreseeability were supported, no cyber-bullying vs. in-school
      main effects (or corresponding interaction effects) were detected. Implications
      for future research and practice, as well as study limitations, are discussed. 

PMID- 24111683
TI  - Biphasic response of mitochondrial biogenesis to oxidative stress in visceral fat
      of diet-induced obesity mice.
AB  - AIMS: Studies in skeletal muscle demonstrate a strong association of
      mitochondrial dysfunction with insulin resistance (IR). However, there is still a
      paucity of knowledge regarding the alteration of mitochondria in adipose tissue
      (AT) in the pathogenesis of IR in obesity. We investigated the mitochondrial
      biogenesis in visceral fat (VF) and subcutaneous fat (SF) in C57BL/6J mice fed a
      high-fat high-sucrose diet for 12 months. RESULTS: Impairment of glucose
      tolerance and insulin sensitivity developed after 1 month of the diet and was
      associated with a prompt increase of VF. The VF adipocytes were larger than those
      in the SF and had increased expressions of HIF-1alpha and p-NFkappaB p65.
      However, the alteration of mitochondrial biogenesis did not occur in the early
      stage when increased intracellular reactive oxygen species (ROS), mitochondrial
      oxygen consumption rate, and mitochondrial ROS emerged at the 1st, 2nd and 2nd
      month, respectively. Until the 6th month, the VF had markedly increased
      mitochondrial DNA content and expression of PGC-1alpha, Tfam, ATP5A, and MnSOD.
      This increase of mitochondrial biogenesis was followed by a generalized decrease
      at the 12th month and the mitochondrial morphology altered markedly. In the late
      stage, although mitochondrial ROS decreased, the increased expression of 8-OHdG
      in VF continued. INNOVATION AND CONCLUSION: These data suggest that IR and ROS
      production occur before the biphasic changes of mitochondrial biogenesis in AT,
      and the VF plays a more crucial role.

PMID- 24111685
TI  - A new stochastic approach for the simulation of agglomeration between colloidal
      particles.
AB  - This paper presents a stochastic approach for the simulation of particle
      agglomeration, which is addressed as a two-step process: first, particles are
      transported by the flow toward each other (collision step) and, second, short
      ranged particle-particle interactions lead either to the formation of an
      agglomerate or prevent it (adhesion step). Particle collisions are treated in the
      framework of Lagrangian approaches where the motions of a large number of
      particles are explicitly tracked. The key idea to detect collisions is to account
      for the whole continuous relative trajectory of particle pairs within each time
      step and not only the initial and final relative distances between two possible
      colliding partners at the beginning and at the end of the time steps. The present
      paper is thus the continuation of a previous work (Mohaupt M., Minier, J.-P.,
      Taniere, A. A new approach for the detection of particle interactions for large
      inertia and colloidal particles in a turbulent flow, Int. J. Multiphase Flow,
      2011, 37, 746-755) and is devoted to an extension of the approach to the
      treatment of particle agglomeration. For that purpose, the attachment step is
      modeled using the DLVO theory (Derjaguin and Landau, Verwey and Overbeek) which
      describes particle-particle interactions as the sum of van der Waals and
      electrostatic forces. The attachment step is coupled with the collision step
      using a common energy balance approach, where particles are assumed to
      agglomerate only if their relative kinetic energy is high enough to overcome the
      maximum repulsive interaction energy between particles. Numerical results
      obtained with this model are shown to compare well with available experimental
      data on agglomeration. These promising results assert the applicability of the
      present modeling approach over a whole range of particle sizes (even nanoscopic)
      and solution conditions (both attractive and repulsive cases). 

PMID- 24111684
TI  - Pancreatic intraepithelial neoplasia and histological changes in non-neoplastic
      pancreas associated with neoadjuvant therapy in patients with pancreatic ductal
      adenocarcinoma.
AB  - AIMS: To study the histological changes in non-neoplastic pancreas and the
      effects on pancreatic intraepithelial neoplasia (PanIN) after neoadjuvant
      chemoradiation therapy (NCRT) for pancreatic ductal adenocarcinoma (PDAC).
      METHODS AND RESULTS: We reviewed the archival H&E slides from 218 patients with
      PDAC who completed NCRT and pancreaticoduodenectomy. Sixty-five patients who
      underwent pancreaticoduodenectomy for PDAC without NCRT were used as controls.
      Various histological features were reviewed and correlated with NCRT and
      survival. The NCRT group had lower densities of PanIN2 (P = 0.004) and PanIN3 (P
      = 0.02) than the control group. The extent of fibrosis, the frequency of neuroma
      like nerve proliferation and the frequency of islet cell aggregation were
      significantly higher in the NCRT group than in the control group (P < 0.05). The
      intensity of inflammation was less in the NCRT group than in the control group (P
      = 0.02). In the NCRT group, patents with moderate to severe fibrosis or grade 2
      inflammation had poorer survival than those with mild fibrosis (P = 0.04) or
      those with grade 0 or grade 1 inflammation (P = 0.003), respectively.
      CONCLUSIONS: Non-neoplastic pancreatic tissue from patients who received NCRT had
      a reduced density of high-grade PanIN lesions, more pancreatic fibrosis, and
      higher frequencies of neuroma-like nerve proliferation and islet cell
      aggregation, but less inflammation, compared to tissue from those who did not
      receive NCRT.

PMID- 24111686
TI  - Novel cilia-dependent pathway activates rapid cyst growth in autosomal dominant
      polycystic kidney disease.

PMID- 24111687
TI  - Isolation of a rice endophytic bacterium, Pantoea sp. Sd-1, with ligninolytic
      activity and characterization of its rice straw degradation ability.
AB  - This study focused on an endophytic bacterial strain, Pantoea sp. Sd-1, which can
      be used to degrade lignin and rice straw. This strain was isolated from rice
      seeds by an optimized surface sterilization method. Pantoea sp. Sd-1 showed
      exceptional ability to degrade rice straw and lignin. In rice straw or kraft
      lignin-containing medium supplemented with 1% glucose and 0.5% peptone, Pantoea
      sp. Sd-1 effectively reduced the rice straw mass weight by 54.5% after 6 days of
      treatment. The strain was also capable of reducing the lignin colour (52.4%) and
      content (69.1%) after 4 days of incubation. The findings suggested that the rice
      endophytic bacterium Pantoea sp. Sd-1 could be applied for the degradation of
      lignocellulose biomass, such as rice straw. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Rice straw, an abundant agricultural by-product in China, is very difficult to
      degrade because of its high lignin content. Due to the immense environmental
      adaptability and biochemical versatility of bacteria, endophytic bacteria are
      useful resources for biodegradation. In this study, we screened for endophytic
      bacteria capable of biodegrading rice straw and lignin and obtained one strain,
      Pantoea sp. Sd-1, with suitable characteristics. Sd-1 could be used for
      degradation of rice straw and lignin, and may play an important role in
      biodegradation of this agricultural by-product.

PMID- 24111688
TI  - Early paracetamol treatment associated with lowered risk of persistent ductus
      arteriosus in very preterm infants.
AB  - OBJECTIVES: Persistent ductus arteriosus (PDA) delays the recovery of very
      preterm infants (VLGA, gestation <32 weeks). Indomethacin/ibuprofen treatment and
      ligation of PDA have complications. As a prostaglandin synthase inhibitor
      paracetamol may also promote the closure of ductus arteriosus. We studied
      retrospectively whether early paracetamol therapy was associated with decreased
      incidence of PDA without adverse events. METHODS: On June 2009, we introduced
      intravenous paracetamol during early respiratory therapy. We included 105 VLGA
      infants who received paracetamol before the age of 72 h. The loading dose was 20
      mg/kg followed by 7.5 mg/kg every 6 hours. The 96 VLGA infants admitted from
      January 2008 to May 2009 without lethal congenital disease were controls. Infants
      dying very early were excluded, leaving 102 paracetamol-exposed and 88 controls
      for analysis. RESULTS: After the introduction of paracetamol, the incidence of
      PDA decreased from 30.7% to 14.7% (p = 0.008). Ibuprofen treatment was given to
      15 paracetamol-treated and to 26 control infants (p = 0.013). Three paracetamol
      exposed and seven control infants required surgery. There was no detectable
      increase in adverse events. CONCLUSIONS: Annual incidence of PDA decreased after
      introduction of paracetamol. Efficacy and safety in promoting the early closure
      of ductus arteriosus remains to be established.

PMID- 24111689
TI  - The presence and distribution of bacteria in dentinal tubules of root filled
      teeth.
AB  - AIM: To investigate the distribution of bacteria within the dentine tubular
      network in a two-chamber model in order to determine a possible route of
      penetration. METHODOLOGY: Root canals of teeth in the experimental group (n = 16)
      were instrumented and root filled using AH26 and gutta-percha. Canals in the
      teeth serving as positive (n = 1) and negative (n = 1) controls were
      instrumented, but not root filled. A two-chamber model was fabricated for each
      root - upper chambers were inoculated weekly with Streptococcus gordonii in brain
      heart infusion broth over 90 days. Turbidity of the lower chamber was checked
      daily. Samples that showed turbidity during the experimental period and samples
      that showed no signs of turbidity at 90 days were fractured and prepared for SEM
      examination. SEM examination for the presence of bacteria within the dentinal
      tubules was performed in the cervical, middle and apical root thirds. In each
      root third, the depth of bacterial penetration was recorded as inner, middle or
      outer dentine. RESULTS: Bacteria were most commonly detected in the cervical
      third (14 of 30 areas). Irrespective of the root third examined, bacteria were
      most commonly detected in the inner dentine (i.e. adjacent to the root canal).
      Only two samples demonstrated bacterial penetration in the outer dentine.
      CONCLUSION: The dentine tubular network provides a potential pathway for bacteria
      to penetrate tooth roots in a two-chamber model.

PMID- 24111690
TI  - Clients' perceptions of service quality and satisfaction at their initial Title X
      family planning visit.
AB  - Family planning service quality and clients' satisfaction with services are
      important determinants of clients' contraceptive use and continuation. We examine
      women's experiences at family planning clinics on a range of dimensions,
      including patient-centered communication (PCC), and identify experiences
      associated with higher ratings of service quality and satisfaction. New female
      clients (n = 748), ages 18-35 years, from clinics in three major metropolitan
      areas completed computer-administered interviews between 2008 and 2009. Factors
      associated with primary outcomes of service quality and satisfaction were
      assessed using multinomial and ordinary logistic regression, respectively. Higher
      scores on a Clinician-Client Centeredness Scale, measuring whether clinicians
      were respectful, listened, and provided thoughtful explanations, were associated
      with perceptions of good quality care and being very satisfied. Higher scores on
      a Clinic Discomfort Scale, measuring staff and waiting-room experiences, were
      associated with reduced satisfaction. Clients' interactions with clinicians,
      especially PCC, influence their perceptions of service quality, whereas their
      satisfaction with services is also influenced by the facility environment. These
      measures are adaptable for agencies to identify the factors contributing to their
      own clients' satisfaction-dissatisfaction with care and perceptions of service
      quality. 

PMID- 24111691
TI  - Antigenotoxic activities of the natural dietary coumarins umbelliferone,
      herniarin and 7-isopentenyloxy coumarin on human lymphocytes exposed to oxidative
      stress.
AB  - The antigenotoxic effects of umbelliferone (UMB), herniarin (HER) and 7
      isopentenyloxy coumarin (7-IP), common natural dietary coumarins, were evaluated
      on the human lymphocyte DNA damage using single-cell gel electrophoresis.
      H(2)O(2)-induced DNA break was measured based on the percentage of DNA in tail,
      and the antigenotoxic effects of the tested compounds were compared with that of
      ascorbic acid (10, 25, 50, 100 and 200 MUM). UMB, HER and 7-IP did not show any
      genotoxicity, as compared to phosphate-buffered saline. Treatment with UMB, HER
      and 7-IP led to a significant reduction in the percentage of DNA in tail induced
      by H(2)O(2) (p < 0.001) at all concentrations. The presence of prenyl moiety in
      the chemical structure of 7-IP may contribute to its better antigenotoxic
      property, compared to UMB. The results of this study showed that 7-IP possessed
      the best antigenotoxic activity among the tested compounds.

PMID- 24111693
TI  - The role of Th17/Tc17 peripheral blood T cells in psoriasis and their positive
      therapeutic response.
AB  - It is known that NB-UVB therapy can suppress a broad range of immune cells, but
      the additional effect of bathing in geothermal seawater still remains unclear. To
      study the influence of treatment on the expression of circulating immune cells
      contributing to the pathogenesis of psoriasis, six patients with psoriasis were
      treated with bathing in geothermal seawater two times daily combined with NB-UVB
      five times/week for 2 weeks and six patients were treated with NB-UVB therapy
      three times/week for 8 weeks. Disease severity (Psoriasis Area and Severity
      Index, PASI), chemokines, inflammatory cytokines, T cells and Toll-like receptors
      in the blood and skin samples were evaluated on enrolment (W0) and at 1 (W1), 3
      (W3) and 8 (W8) weeks. Compared with healthy controls, psoriasis patients with
      active disease had significantly higher proportion of peripheral CLA+ T cells
      expressing CCR10 and CD103 and T cells with both Th1/Tc1 (CD4+/CD8+ IFN-gamma+ or
      TNF-alpha+ cells) and Th17/Tc17 (CD4+CD45R0+IL-23R+, CD4+/CD8+ IL-17A+ or IL-22+
      cells) phenotypes. Both treatments gave a significant clinical effect; however,
      bathing in geothermal seawater combined with NB-UVB therapy was more effective
      than NB-UVB therapy alone. This clinical improvement was reflected by a reduction
      in circulating CLA+ peripheral blood T cells and by a decreased Th1/Th17 and
      Tc1/Tc17 inflammatory response. These findings suggest that the inflammatory
      response in psoriasis is predominantly driven by both CD4+ and CD8+ skin-homing
      tissue retaining T cells of the Th17/Tc17 lineages.

PMID- 24111694
TI  - White spot syndrome virus epizootic in cultured Pacific white shrimp Litopenaeus
      vannamei (Boone) in Taiwan.
AB  - White spot syndrome virus (WSSV) has caused significant losses in shrimp farms
      worldwide. Between 2004 and 2006, Pacific white shrimp Litopenaeus vannamei
      (Boone) were collected from 220 farms in Taiwan to determine the prevalence and
      impact of WSSV infection on the shrimp farm industry. Polymerase chain reaction
      (PCR) analysis detected WSSV in shrimp from 26% of farms. Juvenile shrimp farms
      had the highest infection levels (38%; 19/50 farms) and brooder shrimp farms had
      the lowest (5%; one of 20 farms). The average extent of infection at each farm
      was as follows for WSSV-positive farms: post-larvae farms, 71%; juvenile farms,
      61%; subadult farms, 62%; adult farms, 49%; and brooder farms, 40%.
      Characteristic white spots, hypertrophied nuclei and basophilic viral inclusion
      bodies were found in the epithelia of gills and tail fans, appendages,
      cephalothorax and hepatopancreas, and virions of WSSV were observed. Of shrimp
      that had WSSV lesions, 100% had lesions on the cephalothorax, 96% in gills and
      tail fans, 91% on appendages and 17% in the hepatopancreas. WSSV was also
      detected in copepoda and crustaceans from the shrimp farms. Sequence comparison
      using the pms146 gene fragment of WSSV showed that isolates from the farms had
      99.7-100% nucleotide sequence identity with four strains in the GenBank database-
      China (AF332093), Taiwan (AF440570 and U50923) and Thailand (AF369029). This is
      the first broad study of WSSV infection in L. vannamei in Taiwan.

PMID- 24111695
TI  - Chiral plasmonic nanostructures on achiral nanopillars.
AB  - Chirality of plasmonic films can be strongly enhanced by three-dimensional (3D)
      out-of-plane geometries. The complexity of lithographic methods currently used to
      produce such structures and other methods utilizing chiral templates impose
      limitations on spectral windows of chiroptical effects, the size of substrates,
      and hence, further research on chiral plasmonics. Here we demonstrate 3D chiral
      plasmonic nanostructures (CPNs) with high optical activity in the visible
      spectral range based on initially achiral nanopillars from ZnO. We made
      asymmetric gold nanoshells on the nanopillars by vacuum evaporation at different
      inclination and rotation angles to achieve controlled symmetry breaking and
      obtained both left- and right-rotating isomers. The attribution of chiral optical
      effects to monolithic enantiomers made in this process was confirmed by
      theoretical calculations based on their geometry established from scanning
      electron microscope (SEM) images. The chirality of the nanoshells is retained
      upon the release from the substrate into a stable dispersion. Deviation of the
      incident angle of light from normal results in increase of polarization rotation
      and chiral g-factor as high as -0.3. This general approach for preparation of
      abiological nanoscale chiral materials can be extended to other out-of plane 3D
      nanostructures. The large area films made on achiral nanopillars are convenient
      for sensors, optical devices, and catalysis. 

PMID- 24111696
TI  - Importance of creatinine clearance for drug dosing in nursing home residents.
AB  - Serum creatinine is often not an adequate measure of renal function, especially
      in advanced age or in physically debilitated patients. Estimated creatinine
      clearance is necessary to decide on usage of drugs such as Metformin. This study
      included 64 nursing home residents with diabetes treated with Metformin.
      Creatinine clearance (CrCl) was calculated by the Cockcroft-Gault equation
      modified for ideal body weight. CrCl more than or equal to 60/mL min was used as
      a cut-off for appropriate use of Metformin. In our sample, 20.3% had renal
      failure when measured by serum creatinine while 56.3% had renal failure when
      measured by CrCl. Age >65 years and women were more likely to be classified as
      normal for serum creatinine but have abnormal creatinine clearance. Use of
      estimated creatinine clearance should be advocated instead of serum creatinine
      when prescribing Metformin, especially for those of older age and among women.

PMID- 24111697
TI  - Extraction of lycopene from tomato paste by ursodeoxycholic acid using the
      selective inclusion complex method.
AB  - Lycopene, a precursor of beta-carotene with well-known antioxidant activity and
      powerful health properties, can be found in many natural products such as tomato
      (Lycopersicon esculentum), watermelon, red pepper, and papaya. Many separation
      methods have been reported for extracting lycopene from its sources. The
      inclusion complex is an effective method for extraction and purification of
      organic chemicals. This procedure has 2 main components: host and guest
      molecules. In this study, lycopene (guest) was extracted from tomato paste by
      ursodeoxycholic acid, the inclusive agent (host). The molecular structure of the
      extracted lycopene was then confirmed by (1) HNMR and its purity was evaluated
      using high-performance liquid chromatography and UV-Vis spectrophotometry
      methods, in comparison with a standard product. The results indicated that the
      proposed separation method was very promising and could be used for the
      extraction and purification of lycopene from tomato paste. 

PMID- 24111698
TI  - Evolution in subdivided plant populations: concepts, recent advances and future
      directions.
AB  - Research into the evolution of subdivided plant populations has long involved the
      study of phenotypic variation across plant geographic ranges and the genetic
      details underlying that variation. Genetic polymorphism at different marker loci
      has also allowed us to infer the long- and short-term histories of gene flow
      within and among populations, including range expansions and colonization
      extinction dynamics. However, the advent of affordable genome-wide sequences for
      large numbers of individuals is opening up new possibilities for the study of
      subdivided populations. In this review, we consider what the new tools and
      technologies may allow us to do. In particular, we encourage researchers to look
      beyond the description of variation and to use genomic tools to address new
      hypotheses, or old ones afresh. Because subdivided plant populations are complex
      structures, we caution researchers away from adopting simplistic interpretations
      of their data, and to consider the patterns they observe in terms of the
      population genetic processes that have given rise to them; here, the genealogical
      framework of the coalescent will continue to be conceptually and analytically
      useful.

PMID- 24111699
TI  - Degradative plasmids from sphingomonads.
AB  - Large plasmids ('megaplasmids') are commonly found in members of the
      Alphaproteobacterial family Sphingomonadaceae ('sphingomonads'). These plasmids
      contribute to the extraordinary catabolic flexibility of this group of organisms,
      which degrade a broad range of recalcitrant xenobiotic compounds. The genomes of
      several sphingomonads have been sequenced during the last years. In the course of
      these studies, also the sequences of several plasmids have been determined. The
      analysis of the published information and the sequences deposited in the public
      databases allowed a first classification of these plasmids into a restricted
      number of groups according to the proteins involved in the initiation of
      replication, plasmid partition and conjugation. The sequence comparisons
      demonstrated that the plasmids from sphingomonads encode for four main groups of
      replication initiation (Rep) proteins. These Rep proteins belong to the protein
      superfamilies RepA_C (Pfam 04796), Rep_3 (Pfam 01051), RPA (Pfam 10134) and HTH
      36 (Pfam 13730). The 'degradative megaplasmids' pNL2, pCAR3, pSWIT02, pCHQ1,
      pISP0, and pISP1, which code for genes involved in the degradation of aromatic
      hydrocarbons, carbazole, dibenzo-p-dioxin and gamma-hexachlorocyclohexane, carry
      Rep proteins which either belong to the RepA_C- (plasmids pNL2, pCAR3, pSWIT02),
      Rep-3- (plasmids pCHQ1, pISP0) or RPA-superfamily (pISP1). The classification of
      these 'degradative megaplasmids' into three groups is also supported by sequence
      comparisons of the proteins involved in plasmid partition (ParAB) and the
      organization of the three genes on the respective plasmids. All analysed
      'degradative megaplasmids' carry genes, which might allow a conjugative transfer
      of the plasmids. Sequence comparisons of these genes suggest the presence of at
      least two types of transfer functions, which either are closer related to the tra
      or vir-genes previously described for plasmids from other sources. 

PMID- 24111700
TI  - Long-term Doppler hemodynamics and effective orifice areas of Edwards SAPIEN and
      medtronic CoreValve prostheses after TAVI.
AB  - BACKGROUND: Although initial hemodynamics of percutaneously implanted aortic
      bioprostheses compare favorably to surgically implanted valves, the durability of
      the flow characteristics remains unknown. As biological prostheses are at
      potential risk for early degeneration, the aim of our study was to compare
      Doppler hemodynamics and effective orifice area (EOA) directly after and at least
      1 year after valve implantation. METHODS: In this monocentric, prospective study,
      we determined peak velocity, peak and mean systolic gradients, and EOA by
      echocardiography in 75 patients (Edwards SAPIEN, n = 20; CoreValve, n = 55) 1
      week (median 7 +/- 25 days) and 1 year (median 378 +/- 157 days, maximum 1034
      days) after transcatheter aortic valve implantation (TAVI). RESULTS: After 12
      months, Doppler performance of the aortic valve prostheses remained unchanged.
      The peak instantaneous velocity was 1.9 +/- 0.4 m/s directly after TAVI versus
      1.8 +/- 0.5 m/s (P = ns) at follow-up, with a mean gradient of 8.5 +/- 3.7 mmHg
      and 8.1 +/- 4.2 (P = ns), respectively. Interestingly, the degree of mitral
      regurgitation (MR) decreased significantly (P = 0.007) over time, and the
      severity of aortic regurgitation (AR) remained unchanged during follow-up (P =
      ns). CONCLUSION: For at least 1 year after TAVI, the excellent Doppler
      hemodynamics and EOA are preserved in transcatheter aortic valve prostheses, and
      the severity of MR decreased significantly. In addition, we found no evidence of
      early valve deterioration or progression of AR.

PMID- 24111701
TI  - Facile synthesis and high anode performance of carbon fiber-interwoven amorphous
      nano-SiOx/graphene for rechargeable lithium batteries.
AB  - We present the first report on carbon fiber-interwoven amorphous nano
      SiOx/graphene prepared by a simple and facile room temperature synthesis of
      amorphous SiOx nanoparticles using silica, followed by their homogeneous
      dispersion with graphene nanosheets and carbon fibers in room temperature aqueous
      solution. Transmission and scanning electron microscopic imaging reveal that
      amorphous SiOx primary nanoparticles are 20-30 nm in diameter and carbon fibers
      are interwoven throughout the secondary particles of 200-300 nm, connecting SiOx
      nanoparticles and graphene nanosheets. Carbon fiber-interwoven nano
      SiO0.37/graphene electrode exhibits impressive cycling performance and rate
      capability up to 5C when evaluated as a rechargeable lithium battery anode,
      delivering discharge capacities of 1579-1263 mAhg(-1) at the C/5 rate with
      capacity retention of 80% and Coulombic efficiencies of 99% over 50 cycles, and
      nearly sustained microstructure. The cycling performance is attributed to
      synergetic effects of amorphous nano-SiOx, strain-tolerant robust microstructure
      with maintained particle connectivity and enhanced electrical conductivity. 

PMID- 24111703
TI  - Human impacts have shaped historical and recent evolution in Aedes aegypti, the
      dengue and yellow fever mosquito.
AB  - Although anthropogenic impacts are often considered harmful to species, human
      modifications to the landscape can actually create novel niches to which other
      species can adapt. These "domestication" processes are especially important in
      the context of arthropod disease vectors, where ecological overlap of vector and
      human populations may lead to epidemics. Here, we present results of a global
      genetic study of one such species, the dengue and yellow fever mosquito, Aedes
      aegypti, whose evolutionary history and current distribution have been profoundly
      shaped by humans. We used DNA sequences of four nuclear genes and 1504 single
      nucleotide polymorphism (SNP) markers developed with restriction-site associated
      DNA (RAD) sequencing to test the hypothesis that Ae. aegypti originated in
      Africa, where a domestic form arose and spread throughout the tropical and
      subtropical world with human trade and movement. Results confirmed African
      ancestry of the species, and supported a single subspeciation event leading to
      the pantropical domestic form. In addition, genetic data strongly supported the
      hypothesis that human trade routes first moved domestic Ae. aegypti out of Africa
      into the New World, followed by a later invasion from the New World into
      Southeast Asia and the Pacific. These patterns of domestication and invasion are
      relevant to many species worldwide, as anthropogenic forces increasingly impact
      evolutionary processes. 

PMID- 24111704
TI  - Analysis of the plasma proteome in COPD: Novel low abundance proteins reflect the
      severity of lung remodeling.
AB  - The search for COPD biomarkers has largely employed a targeted approach that
      focuses on plasma proteins involved in the systemic inflammatory response and in
      lung injury and repair. This proof of concept study was designed to test the idea
      that an open, unbiased, in-depth proteomics approach could identify novel, low
      abundance plasma proteins i.e., ng/mL concentration, which could serve as
      potential biomarkers. Differentially expressed proteins were identified in a
      discovery group with severe COPD (FEV1 <45% predicted; n = 10). Subjects with
      normal lung function matched for age, sex, ethnicity and smoking history served
      as controls (n = 10). Pooled plasma from each group was exhaustively
      immunodepleted of abundant proteins, d separated by 1-D gel electrophoresis and
      extensively fractionated prior to LC-tandem mass spectroscopy (GeLC-MS). Thirty
      one differentially expressed proteins were identified in the discovery group
      including markers of lung defense against oxidant stress, alveolar macrophage
      activation, and lung tissue injury and repair. Four of the 31 proteins (i.e.,
      GRP78, soluble CD163, IL1AP and MSPT9) were measured in a separate verification
      group of 80 subjects with varying COPD severity by immunoassay. All 4 were
      significantly altered in COPD and 2 (GRP78 and soluble CD163) correlated with
      both FEV1 and the extent of emphysema. In-depth, plasma proteomic analysis
      identified a group of novel, differentially expressed, low abundance proteins
      that reflect known pathogenic mechanisms and the severity of lung remodeling in
      COPD. These proteins may also prove useful as COPD biomarkers.

PMID- 24111705
TI  - Postpartum voiding dysfunction: identifying the risk factors.
AB  - BACKGROUND: Postpartum urinary retention (PPUR) (also known as voiding
      dysfunction) is a common problem, defined as the inability to completely void
      after giving birth. If voiding dysfunction is not recognised, bladder
      overdistension can lead to denervation, detrusor atony and prolonged voiding
      dysfunction. AIM: To describe the incidence of PPUR amongst postpartum women
      undergoing routine bladder scanning and to identify the factors that lead to
      postpartum voiding dysfunction. METHODS: A retrospective analysis of all
      postpartum women at Mater Health Services, Brisbane between February and December
      2012 was undertaken. Routinely collected postvoid residual bladder volumes
      (PVRBV) were reported using a bladder scanner at four and six hours and two to
      three days postbirth or following removal of an indwelling catheter (IDC). The
      characteristics of women with or without increased PVRBV were analysed. RESULTS:
      Postvoid residual bladder volumes at four-hours postbirth/removal of IDC were
      available for 5558 women of whom 281 (5.1%) had a residual volume measured >150
      mL. Obstetric factors explored included mode of birth, method of analgesia or
      anaesthesia, duration of labour, degree of perineal trauma, birth weight,
      gestation, parity, maternal age and body mass index. After controlling for
      confounders, nulliparity (aOR 1.53; 95% CI 1.05-2.26), birth by caesarean section
      (aOR 2.21; 95% CI 1.10-4.41) and 3rd/4th degree perineal trauma (aOR 2.01; 95% CI
      1.09-3.72) were significant independent predictors of PPUR. CONCLUSION: Following
      the introduction of a protocol of timed voiding and routine measurement of PVRBV
      after birth/removal of IDC, PPUR is uncommon. Adopting a risk-factor-based
      approach to PVRBV screening is not supported by these data.

PMID- 24111706
TI  - Development of anterior inferior cerebellar artery pseudoaneurysm after gamma
      knife surgery for vestibular schwannoma. A case report and review of the
      literature.
AB  - Gamma knife surgery (GKS) is a well-established modality for controlling the
      progression of vestibular schwannomas. Adverse effects of this treatment are
      extremely rare but include cyst formation and malignant transformation. We report
      a case of anterior inferior cerebellar artery (AICA) pseudoaneurysm development
      rupture presenting as a poor WFNS grade subarachnoid haemorrhage. This is only
      the fourth case of aneurysm development (AICA aneurysm) following GKS reported
      but due to its serious nature we believe this potential complication warrants
      awareness in those offering this treatment.

PMID- 24111702
TI  - Statins as regulators of redox state in the vascular endothelium: beyond lipid
      lowering.
AB  - SIGNIFICANCE: Endothelial dysfunction and the imbalance between nitric oxide (NO)
      and reactive oxygen species production in the vascular endothelium are important
      early steps in atherogenesis, a major socioeconomic health problem. Statins have
      well-established roles in primary and secondary prevention of cardiovascular
      disease (CVD), due to both their lipid-lowering capacity and their pleiotropic
      properties. It is therefore important to understand the mechanisms by which
      statins can modify endothelial function and affect atherogenesis. RECENT
      ADVANCES: In the last decade, the concept of statin pleiotropy has been
      reinforced by a large number of cell culture, animal, and translational studies.
      Statins have been shown to suppress the activity of pro-oxidant enzymes (such as
      NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium.
      At the same time, they enhance endothelial NO synthase expression and activity
      while they also improve its enzymatic coupling. This leads to increased NO
      bioavailability and improved endothelial function. CRITICAL ISSUES: Despite
      significant recent advances, the exact mechanisms of statin pleitropy are still
      only partially understood. The vast majority of the published literature relies
      on animal studies, while the actual mechanistic studies in humans are limited.
      FUTURE DIRECTIONS: The success of statins as endothelium redox-modifying agents
      with a direct impact on clinical outcome highlights the importance of the
      endothelium as a therapeutic target in CVD. Better understanding of the
      mechanisms that underlie endothelial dysfunction could lead to the design of
      novel therapeutic strategies that target the vascular endothelium for the
      prevention and treatment of CVD.

PMID- 24111707
TI  - The validity of EORTC GBM prognostic calculator on survival of GBM patients in
      the West of Scotland.
AB  - OBJECTIVE: It is now accepted that the addition of temozolomide to radiotherapy
      in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM)
      significantly improves survival. In 2008, a subanalysis of the original study
      data was performed, and an online "GBM Calculator" was made available on the
      European Organisation for Research and Treatment of Cancer (EORTC) website
      allowing users to estimate patients' survival outcomes. We tested this calculator
      against actual local survival data to validate its use in our patients. MATERIALS
      AND METHODS: Prospectively collected clinical data were analysed on 105
      consecutive patients receiving concurrent chemoradiotherapy following surgical
      treatment of GBM between December 2004 and February 2009. Using the EORTC online
      calculator, survival outcomes were generated for these patients and compared with
      their actual survival. RESULTS: The median overall survival for the entire cohort
      was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival
      of 65.7% and 19%, respectively. This is in comparison to the median overall
      predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and
      39.5%, respectively. Case by case analysis also showed that the survival was
      overestimated in nearly 80% of patients. Subgroup analyses showed similar
      overestimation of patients' survival, except calculator Model 3 which utilised
      MGMT status. CONCLUSION: Use of the EORTC GBM prognostic calculator would have
      overestimated the survival of the majority of our patients with GBM. Uncertainty
      exists as to the cause of overestimation in the cohort although local
      socioeconomic factors might play a role. The different calculator models yielded
      different outcomes and the "best" predictor of survival for the cohort under
      study utilised the tumour MGMT status. We would strongly encourage similar local
      studies of validity testing prior to employing the online prognostic calculator
      for other population groups.

PMID- 24111708
TI  - A survival analysis of GBM patients in the West of Scotland pre- and post
      introduction of the Stupp regime.
AB  - OBJECTIVE: It is now accepted that the concomitant administration of temozolomide
      with radiotherapy (Stupp regime), in the treatment of patients with newly
      diagnosed glioblastoma multiforme (GBM), significantly improves survival and this
      practice has been adopted locally since 2004. However, survival outcomes in
      cancer can vary in different population groups, and outcomes can be affected by a
      number of local factors including socioeconomic status. In the West of Scotland,
      we have one of the worse socioeconomic status and overall health record for a
      western European country. With the ongoing reorganisation and rationalisation in
      the National Health Service, the addition of prolonged courses of chemotherapy to
      patients' management significantly adds to the financial burden of a cash
      stripped NHS. A survival analysis in patients with GBM was therefore performed,
      comparing outcomes of pre- and post-introduction of the Stupp regime, to justify
      the current practice. MATERIALS AND METHODS: Prospectively collected clinical
      data were analysed in 105 consecutive patients receiving concurrent
      chemoradiotherapy (Stupp regime) following surgical treatment of GBM between
      December 2004 and February 2009. This was compared to those of 106 consecutive
      GBM patients who had radical radiotherapy (pre-Stupp regime) post-surgery between
      January 2001 and February 2006. RESULTS: The median overall survival for the post
      Stupp cohort was 15.3 months (range, 2.83-50.5 months), with 1-year and 2-year
      overall survival rates of 65.7% and 19%, respectively. This was in comparison
      with the median overall pre-Stupp survival of 10.7 months, with 1-year and 2-year
      survival rates of 42.6% and 12%, respectively (log-rank test, p < 0.001).
      Multivariate Cox regression analysis showed that independent prognostic factors
      for better survival were younger age, greater extent of surgical resection and a
      post-operative chemoradiotherapy regime. CONCLUSION: Significant survival benefit
      has been achieved, following the introduction of the Stupp regime, in GBM
      patients in the West of Scotland.

PMID- 24111709
TI  - The role of CT body scans in the investigation of patients with newly diagnosed
      brain tumours.
AB  - OBJECTIVE: In the UK approximately 4000 patients are diagnosed with brain tumours
      each year. Many patients undergo CT scans of the chest, abdomen and pelvis as
      part of the investigation of such tumours. We aimed to determine the value of CT
      body scans in patients with newly diagnosed brain tumours. METHODS: We
      retrospectively reviewed the minutes of our neuro-oncology multidisciplinary team
      (MDT) meetings over a 12-month period to identify patients with a new
      radiological diagnosis of a brain tumour. Patients were divided into groups based
      on radiological diagnosis. Histology results were obtained for patients who
      underwent surgery. Results of CT body scans were obtained. RESULTS: A total of
      261 patients were identified. Sixty percent had radiological primary brain
      tumours and 40% had secondary brain tumours. Concordance between radiological and
      histological diagnoses was high (97% for radiological primary brain tumours, and
      83% for radiological secondary brain tumours). CT body scans demonstrated primary
      lesions in 90% of radiological secondary brain tumours. Thirty-four percent of
      patients with a radiological diagnosis of primary brain tumour underwent CT body
      scans. The majority of these scans were normal (78%). CONCLUSION: The ability of
      a specialist neuro-oncology MDT to correctly identify primary and secondary brain
      tumours on initial imaging is high. If the radiological diagnosis is of a
      secondary brain tumour, then CT body scans are essential. If the radiological
      diagnosis is of a primary brain tumour, then CT scans of the body are likely to
      add little to patient management.

PMID- 24111710
TI  - Public disclosure of surgeon's results--pituitary surgery.
AB  - OBJECTIVE: There are few agreed quantifiable outcome measures in pituitary
      surgery. The goal of this study is to present the measurement of resection volume
      after surgery for pituitary tumours as a surgeon-specific outcome measure that
      may have use in illustrating the performance of individual surgeons internally
      and externally, and contribute to quality improvement in pituitary surgery.
      METHOD: The authors used an existing validated method to measure the volume of
      pituitary tumours. This method was used to retrospectively assess the extent of
      resection (EOR) in all patients undergoing pituitary surgery for tumour volume
      reduction over a 3-year period in Leeds, UK. Three surgeons and two techniques
      (endonasal transsphenoidal surgery and conventional microscopic surgery) were
      compared. The results are summarised using Funnel plot methodology. RESULTS: The
      overall mean EOR for the 3 years of study was 54%. There was no difference
      between endoscopic and microscopic techniques in terms of EOR. Significant
      differences were found between surgeons' case mix (as estimated by preoperative
      tumour size) and EOR. One surgeon had smaller tumour cases at operation than the
      other two surgeons (p = 0.004). One surgeon achieved larger resections than the
      two other surgeons (p = 0.038 and 0.005). CONCLUSIONS: Measuring pituitary
      volumes manually using segmentation methods and existing software is possible for
      surgeons and provides valuable information on individual surgeon performance and
      departmental practice. A simple retrospective review of 3 years of practice has
      demonstrated that surgeons have different case-mix and their EOR can vary within
      safe limits. During a period of transition when we changed personnel and
      technique, the EOR was little affected and this was reassuring from a governance
      perspective. Performance assessment for low-volume conditions is possible .

PMID- 24111711
TI  - Stability of omega-3 LC-PUFA-rich photoautotrophic microalgal oils compared to
      commercially available omega-3 LC-PUFA oils.
AB  - Microalgae are the primary producers of omega-3 LC-PUFA, which are known for
      their health benefits. Their oil may thus be a potential alternative for fish
      oil. However, oxidative and hydrolytic stability of omega-3 LC-PUFA oils are
      important parameters. The purpose of this work was therefore to evaluate these
      parameters in oils from photoautotrophic microalgae (Isochrysis, Phaeodactylum,
      Nannochloropsis gaditana, and Nannochloropsis sp.) obtained with
      hexane/isopropanol (HI) and hexane (H) and compare them with commercial omega-3
      LC-PUFA oils. When the results of both the primary and secondary oxidation
      parameters were put together, it was clear that fish, tuna, and heterotrophic
      microalgae oil are the least oxidatively stable oils, whereas krill oil and the
      microalgae oils performed better. The microalgal HI oils were shown to be more
      oxidatively stable than the microalgal H oils. The hydrolytic stability was shown
      not to be a problem during the storage of any of the oils.

PMID- 24111712
TI  - Changes of detergent-resistant plasma membrane proteins in oat and rye during
      cold acclimation: association with differential freezing tolerance.
AB  - Cold acclimation (CA) results in an increase in freezing tolerance of plants,
      which is closely associated to functional changes of the plasma membrane (PM).
      Although proteomic studies have revealed compositional changes of the PM during
      CA, there has been no large-scale study of how the microdomains in the PM, which
      contains specific lipids and proteins, change during CA. Therefore, we conducted
      semiquantitative shotgun proteomics using microdomain-enriched detergent
      resistant membrane (DRM) fractions extracted from low freezing-tolerant oat and
      highly freezing-tolerant rye. We identified 740 and 809 DRM proteins in oat and
      rye, respectively. Among the proteins identified, the abundances of a variety of
      proteins, such as P-type ATPase and aquaporins, were affected by CA in both oat
      and rye. Some CA-responsive proteins in the DRM fractions, such as heat shock
      protein 70, changed differently in oat and rye. In addition, changes in
      lipocalins and sugar transporters in the DRM fractions were different from those
      found in total PM fraction during CA. This is the first report to describe
      compositional changes in the DRM during CA. The proteomic profiles obtained in
      the present study hint at many possible microdomain functions associated with CA
      and freezing tolerance. 

PMID- 24111713
TI  - Genetics of hypertrophic cardiomyopathy in Norway.
AB  - Genetic testing for hypertrophic cardiomyopathy (HCM) became available in Norway
      in 2003. Here, we describe the results of this testing in probands with HCM
      referred until the end of 2012. The translated exons of MYBPC3, MYH7, TNNI3,
      TNNT2, MYL2 and MYL3 were analyzed in two groups of probands. In Group 1,
      comprising 696 probands above 1 year of age, a mutation was found in 203 patients
      (29.2%). Of those, 5.9% were carriers of two mutations. Mean age in double
      mutation carriers, single mutation carriers and mutation negative probands was 44
      years (+/- 19 years), 50 years (+/- 5 years) and 55 years (+/- 6 years),
      respectively. In Group 2, comprising 26 infants below the age of 1, a mutation
      was found in 15.4%. A total of 120 different mutations were found of which 51
      (42.5%) were novel.

PMID- 24111714
TI  - Penicillin facilitates the entry of antisense constructs into Streptococcus
      mutans.
AB  - Antisense oligonucleotides (AS-ODN) target genes in a sequence-specific manner
      inhibit gene function and have potential use as antimicrobial agents. Cell
      barriers, such as peptidoglycan, cell surface proteins and lipopolysaccharide
      membranes, prevent delivery of AS-ODN into the bacterial cell, limiting their use
      as an effective treatment option. The beta-lactam antibiotic penicillin was
      examined for its ability to deliver phosphorothioate oligodeoxyribonucleotides
      (PS-ODNs) and gamma(32) P-ODN into Streptococcus mutans OMZ175. Treatment of lag
      phase S. mutans OMZ175 cells with penicillin and FBA (PS-ODN targeting the
      fructose-biphosphate aldolase gene), resulted in prolonged suppression of growth
      (> 24 h) and fba expression (656.9 +/- 194.4-fold decrease at 5 h). Suppression
      of both cell growth and fba expression corresponded with a greater amount of
      gamma(32) P-ODN becoming cell associated, with a maximum gamma(32) P-ODN
      concentration per cell achieved 5 h after penicillin treatment (6.50 +/- 1.39 *
      10(8) molecules per CFU). This study confirms that for S. mutans OMZ175, the
      peptidoglycan layer acts as a major barrier preventing AS-ODN penetration and
      suggests that the use of agents such as penicillin that interfere with
      peptidoglycan integrity can significantly increase the uptake of PS-ODN by these
      cells. 

PMID- 24111715
TI  - Increased accumulation of CD16+ monocytes at local sites of inflammation in
      patients with chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) display a high prevalence of
      cardiovascular events and acute infections. Potential effector cells are the
      CD16(+) monocytes, known to be increased in the peripheral circulation in CKD.
      The aim of this study was to assess the expression of CD16 and CX3 CR1 on
      peripheral and in vivo extravasated monocytes in patients with CKD (GFR < 20
      ml/min * 1.73 m2) using flow cytometry. In vivo extravasated monocytes were
      collected from a local inflammatory site, induced by a skin blistering technique.
      Soluble markers were assessed by Luminex. The number of CD16(+) monocytes was
      significantly higher in patients with CKD compared with healthy subjects, both in
      the peripheral circulation (P < 0.05) and at the site of induced inflammation (P
      < 0.001). Patients with CKD displayed significantly higher concentration of
      soluble CX3 CL1 both in the peripheral circulation (P < 0.01) and in the
      interstitial fluid (P < 0.001). In addition, patients with CKD had a
      significantly higher concentration of TNF-alpha in the peripheral circulation (P
      < 0.001). On the contrary, at the inflammatory site, concentrations of both TNF
      alpha and IL-10 were significantly lower in patients with CKD compared with
      healthy controls (P < 0.05 for both). In conclusion, patients with CKD have an
      increased percentage of CD16(+) monocytes in both circulation and at the
      inflammatory site, and this finding is in concurrence with simultaneous changes
      in CX3 CR1. Together with distorted TNF-alpha and IL-10 levels, this may have
      potential impact on the altered inflammatory response in CKD.

PMID- 24111716
TI  - Qualitative and quantitative assessment on the use of magnetic nanoparticles for
      glycopeptide enrichment.
AB  - Glycoproteomics represent the field of study of the dynamic changes occurring
      among glycoconjugates within the cellular compartments. Changes in glycosylation
      have been linked to various diseases, including metastatic carcinomas in which
      the 9 carbon sialic acid moiety has been shown to play a prominent role. The
      common method used to study these aberrant changes most often includes a mass
      spectrometer at some stage in the workflow. However, serum samples contain many
      proteins which inhibit the analysis of these glycosylation changes, and ergo,
      enrichment steps are employed as a measure to help alleviate this ailment.
      Routinely, this is accomplished using lectins, either alone or in combination, to
      retrieve proteins with specific sugar linkages within the serum sample. This
      methodology, although known to be very specific, requires many washing steps,
      making it a cumbersome addition to a high throughput workflow. Presented here is
      an alternative protocol using custom-made amine functionalized magnetic
      nanoparticles (MNP) which are nearly 4* smaller than those used before for
      similar purposes. The developed protocol is based on both hydrophilic interaction
      and weak anion exchange principles, allowing it to target glycopeptides but, more
      specifically, those which contain sialylation. For quantification purposes,
      tandem mass tags from Thermo Scientific were utilized to compare the enrichment
      efficiencies between the magnetic nanoparticle method and a commercially
      available glycopeptide enrichment kit offered through EMD Millipore. The MNP
      method is fast (~10 min) and simple and can quantitatively and qualitatively
      enrich sialylated glycopeptides more than the commercially available kit.

PMID- 24111717
TI  - Effects of a 28-day oral exposure to a 5-chloro-2-methyl-4-isothiazolin-3-one and
      2-methyl-4-isothiazolin-3-one biocide formulation in Sprague-Dawley rats.
AB  - Biocides are added to biodiesels to prevent degradation resulting from microbial
      growth. A 28-day repeated oral dose study was conducted to assess a potential
      risk arising from ingestion of isothiazolinone biocides in biodiesels. A mixture
      of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one
      (CMIT/MIT) diluted in corn oil was administered by gavage to male and female rats
      at 0, 0.26, 0.78, 2.33 and 7.0 mg/kg body weight per day. Rat water and food
      consumption was monitored. At the end of the dosing period, organs were weighed
      and histological examinations performed. Hematology, serum clinical chemistry and
      biomarkers of inflammation were assessed. Reduction of serum triglyceride levels
      in males and induction of hepatic phase 1 xenobiotic metabolizing enzymes in
      females accompanied by subtle histological changes in the liver were observed at
      the highest CMIT/MIT exposure. These changes were more indicative of an adaptive,
      reversible response than overt toxicity. Based on recommended levels for the
      control of microbial growth in fuels, CMIT/MIT contained in accidentally ingested
      biodiesels is not expected to represent a significant health risk.

PMID- 24111718
TI  - Changes in osmol gap in chronic kidney disease: an exploratory study.
AB  - AIM: There is no data on osmol gap (OG) in chronic kidney disease (CKD) by stage
      and limited data on OG in adults on maintenance hemodialysis (HD). We aimed to
      examine the OG between different stages of CKD and to compare the OG pre- and
      post-HD in those on maintenance HD. METHODS: We conducted a cross-sectional study
      of 67 patients. The participants were divided into six groups: Group 1-reference
      group (normal renal function), Group 2-CKD stage 2; Group 3-CKD stage 3; Group 4
      CKD stage 4; Group 5-CKD stage 5 and not on dialysis. Group 6 were subjects on
      maintenance HD. RESULTS: The means of OG +/- standard deviation of Groups 1-6
      were 15.25 +/- 3.0, 20.73 +/- 2.68, 22.85 +/- 6.99, 24.11 +/- 3.64, 25.15 +/-
      5.06, and 28.88 +/- 3.45, respectively (p < 0.001). In the HD group, the
      difference between the pre-HD and post-HD OG was statistically significant (p <
      0.001). CONCLUSION: There is a statistically significant upward trend for OG as
      CKD stage increases. The OG is elevated in patients on maintenance HD and is
      normalized by the HD. OG can be a valuable additional tool to suggest CKD stage
      and serve as a marker of dialysis adequacy.

PMID- 24111719
TI  - Macrophage infiltration and stress-signaling in omental and subcutaneous adipose
      tissue in diabetic pregnancies.
AB  - OBJECTIVE: To examine if, as in obesity, pregnancies complicated by gestational
      diabetes mellitus (GDM) exhibit increased macrophage infiltration and activated
      MAP-kinases in omental adipose tissue. METHODS: Paired omental (OM) and abdominal
      subcutaneous (SC) fat samples were collected from 11 GDM and 20 normal
      pregnancies during cesarean delivery. Tissues were stained to detect macrophages,
      and analyzed to assess MAP-kinases. RESULTS: OM had higher macrophage counts than
      SC in GDM (6.10 +/- 2.20 versus 2.53 +/- 1.45, p = 0.04), but not in normal
      pregnancies (p = 0.346). GDM pregnancies had more macrophages than normal
      pregnancies in OM (6.10 +/- 2.20 versus 1.29 +/- 0.55, p = 0.01), while only a
      trend was observed in SC fat (p = 0.08). Significant correlation (R = 0.619, p =
      0.005) was observed between OM-macrophage infiltration and insulin resistance.
      Using multivariate analysis, only obesity independently associated with GDM.
      Expression of total p38MAP-kinase was higher in OM versus SC in both normal and
      GDM pregnancies, without significant differences between these groups. However,
      expression of activated p-p38MAP-kinase, and its upstream kinase MKK4, was
      comparable between fat depots. CONCLUSION: GDM pregnancies demonstrate increased
      macrophage infiltration to OM fat, correlating with higher insulin resistance. As
      in non-pregnant-patients obesity and OM macrophage infiltration may be on the
      same causal pathway, leading to GDM. Yet, this occurs without activation of
      p38MAP-kinase signaling.

PMID- 24111720
TI  - Effect of a sublethal high-pressure homogenization treatment on the fatty acid
      membrane composition of probiotic lactobacilli.
AB  - High-pressure homogenization (HPH) has been proposed to be applied directly to
      lactic acid bacterial cells at sublethal levels to enhance some functional
      properties. As the principal target of HPH are the cell surface envelope
      structures, the aim of this work was to study the effect of a HPH treatment,
      applied at 50 MPa, on cell membrane stress responses of already-known functional
      strains, isolated from Argentinean products. Specifically, the membrane fatty
      acid composition of cells before and after the sublethal treatment was
      investigated, and the results showed that plasma membranes, their level of
      unsaturation and their composition are involved in response mechanisms adopted by
      microbial cells when subjected to a sublethal HPH stress. In fact, the data
      obtained demonstrated that the treatment was able to modify the fatty acid
      profile of the different strains, although a uniform response was not observed.
      Further studies are necessary both to elucidate the role of each fatty acid in
      the cell response mechanisms and to clarify the changes in membrane compositions
      induced by HPH treatment also in relation to the applicative potential of this
      technique. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributed to
      understand the response mechanisms activated in cells exposed to pressure stress.
      It has been demonstrated that high-pressure homogenization (HPH) treatments,
      conducted at sublethal levels, could increase some important functional and
      technological characteristics of nonintestinal probiotic strains. The findings of
      this paper can contribute to elucidate the mechanisms through which these
      treatments can modify these strain probiotic properties that are related to
      outermost cell structures, also principal target of HPH.

PMID- 24111723
TI  - Auxin response factor (OsARF12), a novel regulator for phosphate homeostasis in
      rice (Oryza sativa).
AB  - Phosphorus (P) is crucial nutrient element for crop growth and development.
      However, the network pathway regulating homeostasis of phosphate (Pi) in crops
      has many molecular breeding unknowns. Here, we report that an auxin response
      factor, OsARF12, functions in Pi homeostasis. Measurement of element content,
      quantitative reverse transcription polymerase chain reaction analysis and acid
      phosphatases (APases) activity assay showed that the osarf12 mutant and
      osarf12/25 double mutant with P-intoxicated phenotypes had higher P
      concentrations, up-regulation of the Pi transporter encoding genes and increased
      APase activity under Pi-sufficient/-deficient (+Pi/-Pi, 0.32/0 mM NaH2 PO4)
      conditions. Transcript analysis revealed that Pi-responsive genes--Phosphate
      starvation (OsIPS)1 and OsIPS2, SYG1/Pho81/XPR1(OsSPX1),
      Sulfoquinovosyldiacylglycerol 2 (OsSQD2), R2R3 MYB transcription factor (OsMYB2P
      1) and Transport Inhibitor Response1 (OsTIR1)--were more abundant in the osarf12
      and osarf12/25 mutants under +Pi/-Pi conditions. Knockout of OsARF12 also
      influenced the transcript abundances of the OsPHR2 gene and its downstream
      components, such as OsMiR399j, OsPHO2, OsMiR827, OsSPX-MFS1 and OsSPX-MFS2.
      Results from -Pi/1-naphthylphthalamic acid (NPA) treatments, and auxin reporter
      DR5::GUS staining suggest that root system alteration and Pi-induced auxin
      response were at least partially controlled by OsARF12. These findings enrich our
      understanding of the biological functions of OsARF12, which also acts in
      regulating Pi homeostasis.

PMID- 24111724
TI  - Understanding narrative effects: the role of discrete negative emotions on
      message processing and attitudes among low-income African American women.
AB  - This study tests the processes through which breast cancer narrative messages are
      effective by taking a functional approach. We explore how discrete negative
      emotions (i.e., sadness, fear, and anger) induced by breast cancer survivor
      stories affect African American women's message processing, recall of message
      content, and attitudinal outcomes. Structural equation modeling was performed for
      narrative and informational versions of a breast cancer screening video shown to
      489 low-income African American women ages 40 years and older. The model was well
      fitted. Sadness enhanced the persuasive process, while fear inhibited it. Sadness
      also helped participants recall more message-relevant content, while fear
      inhibited recall. Anger was not related to the persuasive process. Implications
      of these findings for narrative research and application are discussed. 

PMID- 24111725
TI  - Content-specific gender differences in emotion ratings from early to late
      adulthood.
AB  - The investigation of gender differences in emotion has attracted much attention
      given the potential ramifications on our understanding of sexual differences in
      disorders involving emotion dysregulation. Yet, research on content-specific
      gender differences across adulthood in emotional responding is lacking. The aims
      of the present study were twofold. First, we sought to investigate to what extent
      gender differences in the self-reported emotional experience are content
      specific. Second, we sought to determine whether gender differences are stable
      across the adult lifespan. We assessed valence and arousal ratings of 14 picture
      series, each of a different content, in 94 men and 118 women aged 20 to 81.
      Compared to women, men reacted more positively to erotic images, whereas women
      rated low-arousing pleasant family scenes and landscapes as particularly
      positive. Women displayed a disposition to respond with greater defensive
      activation (i.e., more negative valence and higher arousal), in particular to the
      most arousing unpleasant contents. Importantly, significant interactions between
      gender and age were not found for any single content. This study makes a novel
      contribution by showing that gender differences in the affective experiences in
      response to different contents persist across the adult lifespan. These findings
      support the "stability hypothesis" of gender differences across age. 

PMID- 24111726
TI  - Effect of interconnection between cervical vagus trunk, epicardial fat pad on
      sinus node function, and atrial fibrillation.
AB  - BACKGROUND: The epicardial fat pad (FP) integrates the autonomic innervation
      between the extrinsic and intrinsic cardiac autonomic nervous system and affects
      atrial electrophysiology and pathophysiology. METHODS: Eighteen dogs were divided
      into two groups: sequential ablation of sinoatrial node FP (SAN-FP) and
      atrioventricular node FP (AVN-FP). Sinus rate (SR), atrial fibrillation (AF)
      inducibility, and effective refractory period (ERP) changes during electrical
      stimulation of the vagus trunk were detected before and after ablation. RESULTS:
      In the SAN-FP group, the SR slowing, increasing AF inducibility, and ERP
      shortening that induced by vagus trunk stimulation were significantly attenuated
      by isolated SAN-FP ablation, compared with the same group prior to ablation (all
      P < 0.05). Subsequent AVN-FP ablation following SAN-FP ablation almost cannot
      produce further attenuation during vagus trunk stimulation, compared with
      isolated SAN-FP ablation (P > 0.05). In the AVN-FP group, SR slowing, increasing
      AF inducibility, and ERP shortening that induced by vagus trunk stimulation were
      completely eliminated by isolated AVN-FP ablation, compared with the same group
      prior to ablation (all P < 0.05). Subsequent SAN-FP ablation following AVN-FP
      ablation produced no further attenuation, compared with isolated AVN-FP ablation
      (P > 0.05). CONCLUSIONS: A neural pathway from the cervical vagus trunk to the
      sinus node and atrium runs through the SAN-FP, but eventually converges at the
      AVN-FP and also suggested that the AVN-FP serves as an "integration center" for
      the SAN-FP to modulate sinus node function. The AVN-FP may play a more critical
      role in the initiation and maintenance of AF.

PMID- 24111727
TI  - Brain circadian oscillators and redox regulation in mammals.
AB  - SIGNIFICANCE: Functional states of organisms vary rhythmically with a period of
      about a day (i.e., circadian). This endogenous dynamic is shaped by day-night
      alternations in light and energy. Mammalian circadian rhythms are orchestrated by
      the hypothalamic suprachiasmatic nucleus (SCN), a brain region specialized for
      timekeeping. These autonomous ~24-h oscillations are cell-based, requiring
      transcription-translation-based regulation. SCN circadian oscillations include
      the maintenance of intrinsic rhythms, sensitivities to input signals, and
      generation of output signals. These change predictably as time proceeds from dawn
      to day, dusk, and through the night. SCN neuronal excitability, a highly energy
      demanding process, also oscillates over ~24 h. The nature of the relationship of
      cellular metabolism and excitability had been unknown. RECENT ADVANCES: Global
      SCN redox state was found to undergo an autonomous circadian rhythm. Redox state
      is relatively reduced in daytime, when neuronal activity is high, and oxidized
      during nighttime, when neurons are relatively inactive. Redox modulates neuronal
      excitability via tight coupling: imposed reducing or oxidizing shifts immediately
      alter membrane excitability. Whereas an intact transcription-translation
      oscillator is necessary for the redox oscillation, metabolic modulation of
      excitability is too rapid to be under clockwork control. CRITICAL ISSUES: Our
      observations lead to the hypothesis that redox state and neuronal activity are
      coupled nontranscriptional circadian oscillators in SCN neurons. Critical issues
      include discovering molecular and cellular substrates and functional consequences
      of this redox oscillator. FUTURE DIRECTIONS: Understanding interdependencies
      between cellular energy metabolism, neuronal activity, and circadian rhythms is
      critical to developing therapeutic strategies for treating neurodegenerative
      diseases and brain metabolic syndromes.

PMID- 24111729
TI  - Validation of acute liver injury cases in a population-based cohort study of oral
      antimicrobial users.
AB  - We conducted a cohort study of acute, noninfectious liver injury among oral
      antimicrobial users. Potential cases were identified in the HealthCore Integrated
      Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009,
      using ICD-9-CM codes primarily for acute and subacute necrosis of the liver,
      hepatic coma, and unspecified hepatitis. Liver test results were used to confirm
      case status according to published criteria. Two physician reviewers experienced
      in studying acute liver injury (blinded to study drug exposures) evaluated data
      abstracted from hospital and emergency department records to validate potential
      cases. Of 715 potential cases having claims associated with any of the primary
      screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295
      (41%) were of uncertain status (records inadequate for validation). Among
      potential cases with adequate medical records, the PPV for presence of any of the
      primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was
      for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation
      of cases of noninfectious liver injury using hospital and emergency department
      medical records continues to represent the preferred approach in studies using
      insurance claims data. 

PMID- 24111730
TI  - Simplified single plane echocardiography is comparable to conventional biplane
      two-dimensional echocardiography in the evaluation of left atrial volume: a study
      validated by three-dimensional echocardiography in 143 individuals.
AB  - The left atrial volume index (LAVI) is a biomarker of diastolic dysfunction and a
      predictor of cardiovascular events. Three-dimensional echocardiography (3DE) is
      highly accurate for LAVI measurements but is not widely available. Furthermore,
      biplane two-dimensional echocardiography (B2DE) may occasionally not be feasible
      due to a suboptimal two-chamber apical view. Simplified single plane two
      dimensional echocardiography (S2DE) could overcome these limitations. We aimed to
      compare the reliability of S2DE with other validated echocardiographic methods in
      the measurement of the LAVI. We examined 143 individuals (54 +/- 13 years old;
      112 with heart disease and 31 healthy volunteers; all with sinus rhythm, with a
      wide range of LAVI). The results for all the individuals were compared with B2DE
      derived LAVIs and validated using 3DE. The LAVIs, as determined using S2DE (32.7
      +/- 13.1 mL/m(2)), B2DE (31.9 +/- 12.7 mL/m(2)), and 3DE (33.1 +/- 13.4 mL/m(2)),
      were not significantly different from each other (P = 0.85). The S2DE-derived
      LAVIs correlated significantly with those obtained using both B2DE (r = 0.98; P <
      0.001) and 3DE (r = 0.93; P < 0.001). The mean difference between the S2DE and
      B2DE measurements was <1.0 mL/m(2). Using the American Society of
      Echocardiography criteria for grading LAVI enlargement (normal, mild, moderate,
      severe), we observed an excellent agreement between the S2DE- and B2DE-derived
      classifications (kappa = 0.89; P < 0.001). S2DE is a simple, rapid, and reliable
      method for LAVI measurement that may expand the use of this important biomarker
      in routine echocardiographic practice.

PMID- 24111728
TI  - Lipid analogues as potential drugs for the regulation of mitochondrial cell
      death.
AB  - The mitochondrion plays an important role in the production of energy as ATP, the
      regulation of cell viability and apoptosis, and the biosynthesis of major
      structural and regulatory molecules, such as lipids. During ATP production,
      reactive oxygen species are generated that alter the intracellular redox state
      and activate apoptosis. Mitochondrial dysfunction is a well-recognized component
      of the pathogenesis of diseases such as cancer. Understanding mitochondrial
      function, and how this is dysregulated in disease, offers the opportunity for the
      development of drug molecules to specifically target such defects. Altered energy
      metabolism in cancer, in which ATP production occurs largely by glycolysis,
      rather than by oxidative phosphorylation, is attributable in part to the up
      regulation of cell survival signalling cascades. These pathways also regulate the
      balance between pro- and anti-apoptotic factors that may determine the rate of
      cell death and proliferation. A number of anti-cancer drugs have been developed
      that target these factors and one of the most promising groups of agents in this
      regard are the lipid-based molecules that act directly or indirectly at the
      mitochondrion. These molecules have emerged in part from an understanding of the
      mitochondrial actions of naturally occurring fatty acids. Some of these agents
      have already entered clinical trials because they specifically target known
      mitochondrial defects in the cancer cell.

PMID- 24111732
TI  - Reproducibility of current classifications of endometrial endometrioid glandular
      proliferations: further evidence supporting a simplified classification.
AB  - AIMS: To compare the reproducibility of the current (2003) World Health
      Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European
      Working Group (EWG) classifications of endometrial endometrioid proliferations.
      METHODS AND RESULTS: Nine expert gynaecological pathologists from Europe and
      North America reviewed 198 endometrial biopsy/curettage specimens originally
      diagnosed as low-grade lesions. All observers were asked to classify the cases by
      using the categories described in each scheme: six for WHO, four for EIN, and
      three for EWG. The results were evaluated by kappa statistics for more than two
      observations. The analysis was repeated using only two major categories (benign
      versus atypical/carcinoma). Both the WHO and EIN classifications showed poor
      interobserver agreement (kappa = 0.337 and kappa = 0.419, respectively), whereas
      the EWG classification showed moderate agreement (kappa = 0.530). Full agreement
      between pathologists occurred in only 28% for the WHO classification, 39% for the
      EIN classification, and 59% for the EWG classification. With only two diagnostic
      categories, kappa values increased in all classifications, but only the EWG
      classification reached a substantial level of agreement (kappa = 0.621);
      similarly, full agreement among all pathologists increased to 70% for the WHO
      classification, 69% for the EIN classification, and 72% for the EWG
      classification. CONCLUSIONS: A two-tier classification of endometrial
      endometrioid proliferative lesions improves reproducibility, and should be
      considered for the diagnosis of endometrial biopsy/curettage specimens.

PMID- 24111731
TI  - Clinical impact of time of day on acute exercise response in COPD.
AB  - The purpose of this pilot study was to determine the impact of time of day on the
      acute response to incremental exercise in chronic obstructive pulmonary disease
      (COPD). Fourteen subjects (nine men) aged 71 +/- 7 years with moderate to severe
      airflow obstruction (FEV1: 58 +/- 13% predicted) followed a counterbalanced
      randomized design, performing three symptom-limited incremental cycling tests at
      8:00, 12:00, and 16:00 hours on different days, each preceded by a spirometry.
      COPD medications were withdrawn prior to testing. No overall time effect was
      found for peak exercise capacity (p = 0.22) or pulmonary function (FEV1, p =
      0.56; FVC, p = 0.79). However, a large effect size (f = 0.48) was observed for
      peak exercise capacity and several pulmonary function parameters. For peak
      exercise capacity, the average within-subject coefficient of variation was 5.5 +/
      3.9% and the average amplitude of change was 7 +/- 5W. Seven subjects (50%)
      showed diurnal changes at levels equal to or beyond the minimal clinically
      important difference for both peak exercise capacity and pulmonary function. In
      this sub-group, peak exercise capacity was greatest at 16:00 hours (p = 0.03, f =
      1.04). No systematic time-of-day effect on peak exercise capacity was obtained in
      COPD patients in the present pilot study. However, based on the observed effect
      size and on the average amplitude of change and within-subject variations seen
      across testing times, the guidelines recommendation that time of day be
      standardized for repeat exercise testing in COPD should be maintained.

PMID- 24111733
TI  - Subclinical hypothyroidism as a risk factor for placental abruption: evidence
      from a low-risk primigravid population.
AB  - BACKGROUND: Subclinical thyroid hypofunction in pregnancy has been shown to have
      an association with neurodevelopmental delay in the offspring. It is unclear
      whether obstetric factors may account for this observation. AIMS: To establish
      the prevalence of subclinical hypothyroidism (SCH) in a low-risk primigravid
      population and to explore its association with obstetric sequelae. MATERIALS AND
      METHODS: Nine hundred and fifty-three primigravid women had thyroid hormone
      indices analysed in the early second trimester. Delivery and neonatal outcomes
      were available for 904 women who met the criteria for inclusion in the study.
      Women with subclinical hypothyroidism (thyroid-stimulating hormone (TSH) values
      at or above the 98th percentile with a normal free thyroxine (fT4)) or isolated
      maternal hypothyroxinaemia (fT4 level at or below the second percentile with a
      normal-range TSH) were compared with biochemically euthyroid controls. Chi
      squared test and analysis of variance were used for statistical analysis.
      RESULTS: The prevalence of SCH or isolated maternal hypothyroxinaemia was 4%.
      Positivity for antithyroid peroxidase (TPO) or antithyroglobulin (ATG) antibodies
      correlated with SCH status (P = 0.02). Placental abruption was observed more
      commonly in the setting of either SCH or isolated maternal hypothyroxinaemia when
      compared with euthyroid controls (P = 0.02 and 0.04, respectively). CONCLUSIONS:
      Subclinical hypothyroidism and isolated maternal hypothyroxinaemia are associated
      with placental abruption. The observation of these effects in this healthy low
      risk population lends weight to the case for antenatal screening for diminished
      thyroid reserve.

PMID- 24111734
TI  - Anomalies in solution behavior of an alkyl aminopolycarboxylic chelating
      surfactant.
AB  - The solution behavior of a DTPA (diethylenetriamine pentaacetic acid)-based
      chelating surfactant, 4-C12-DTPA, has been studied by tensiometry and NMR
      diffusometry. In the absence of metal ions, the eight donor atoms in the
      headgroup are titrating, and the charge of the headgroup can thus be tuned by
      altering the pH. 4-C12-DTPA changes from cationic at very low pH, over a number
      of zwitterionic species as the pH is increased, and eventually becomes anionic at
      high pH. Around the isoelectric point, the chelating surfactant precipitated. The
      solution properties, studied above the solubility gap, were found strongly pH
      dependent. When increasing the amount of negative charges in the headgroup, by
      increasing the pH, the adsorption efficiency was reduced and the cmc was
      increased. An optimum in surface tension reduction was found at pH 5, due to a
      proper balance between protonated and dissociated groups. Anomalies between
      surface tension measurements and NMR diffusometry in determination of cmc
      revealed a more complex relation between surface tension, surface coverage, and
      cmc than usually considered, which is not in line with the common interpretation
      of the Gibbs adsorption equation. At some of the investigated pH levels,
      measurements of bulk pH could confirm the location of cmc, due to the increased
      protonation of micelles compared to monomers in solution. The adsorption of
      monomers to the air-water interface showed unusually slow time dependence,
      evident from decreasing surface tension for several hours. This is explained by
      rearrangements of the large head groups to reduce the headgroup area and increase
      the packing parameter. 

PMID- 24111735
TI  - Unanswered questions in headache: so what is photophobia, anyway?
AB  - Photophobia refers to a sensory disturbance provoked by light. However, because
      it arises distinctly in a broad range of clinical conditions, its definition
      remains elusive. Many underscore the painful sensory aspects of photophobia,
      while others emphasize its unpleasant, affective qualities. To add further
      complexity, recent discoveries in photophobia research have raised disparate and
      potentially conflicting results. In this installment of an occasional series, we
      asked clinicians and scientists to give their interpretation of what these
      discoveries tell us about photophobia in the clinic, and vice versa. 

PMID- 24111736
TI  - Design and synthesis of laser-activatable tetrazoles for a fast and fluorogenic
      red-emitting 1,3-dipolar cycloaddition reaction.
AB  - The design and synthesis of a new class of laser light activatable tetrazoles
      with extended pi-systems is reported. Upon 405 nm laser light irradiation, these
      bithiophene-substituted tetrazoles underwent extremely fast 1,3-dipolar
      cycloaddition reactions with dimethyl fumarate with second-order rate constants
      approaching 4000 M(-1) s(-1). The resulting pyrazoline cycloadducts exhibited
      solvent-dependent red fluorescence, making these tetrazoles potentially useful as
      fluorogenic probes for detecting alkenes in vivo. 

PMID- 24111737
TI  - Caramel popcorn shaped silicon particle with carbon coating as a high performance
      anode material for Li-ion batteries.
AB  - Silicon is a very promising anode material for lithium ion batteries. It has a
      4200 mAh/g theoretical capacity, which is ten times higher than that of
      commercial graphite anodes. However, when lithium ions diffuse to Si anodes, the
      volume of Si will expand to almost 400% of its initial size and lead to the crack
      of Si. Such a huge volume change and crack cause significant capacity loss.
      Meanwhile, with the crack of Si particles, the conductivity between the electrode
      and the current collector drops. Moreover, the solid electrolyte interphase
      (SEI), which is generated during the cycling, reduces the discharge capacity.
      These issues must be addressed for widespread application of this material. In
      this work, caramel popcorn shaped porous silicon particles with carbon coating
      are fabricated by a set of simple chemical methods as active anode material. Si
      particles are etched to form a porous structure. The pores in Si provide space
      for the volume expansion and liquid electrolyte diffusion. A layer of amorphous
      carbon is formed inside the pores, which gives an excellent isolation between the
      Si particle and electrolyte, so that the formation of the SEI layer is
      stabilized. Meanwhile, this novel structure enhances the mechanical properties of
      the Si particles, and the crack phenomenon caused by the volume change is
      significantly restrained. Therefore, an excellent cycle life under a high rate
      for the novel Si electrode is achieved. 

PMID- 24111738
TI  - Lactoferrin administration into the nostril alleviates murine allergic rhinitis
      and its mechanisms.
AB  - Lactoferrin (LF) can downregulate allergic airway inflammation in asthma.
      However, the in vivo effect of exogenous LF on allergic rhinitis (AR), a disease
      attributed to airway inflammation, has yet to be determined. We investigated the
      effect of intranasal administration recombinant human (rh) LF and its underlying
      mechanisms on AR in BALB/c mice. Multiple parameters of allergic responses were
      evaluated to determine the effect of rhLF. We found that the number of
      eosinophils and goblet cells, as well as mRNA and protein expression of type 2
      helper T (Th2), Th17 and regulatory T (Treg) cells in the nasal cavity, was
      significantly upregulated in AR mice compared with the controls, Conversely,
      administration of rhLF prior to or after intranasal ovalbumin challenge markedly
      downregulated these same parameters. Th1-specific mRNA and protein expression in
      the nasal cavity of the controls was not different from that in AR mice, but
      expression significantly increased with rhLF treatment. The mRNA and protein
      expression of endogenous LF in the nasal cavity was significantly downregulated
      in AR mice compared with the controls. However, after rhLF treatment, endogenous
      LF mRNA and protein expression was significantly upregulated. Exogenous rhLF
      inhibited allergic inflammation in AR mice, most likely by promoting the
      endogenous LF expression and skewing T cells to a Th1, but not a Th2 and Th17
      phenotype in the nasal mucosa. Our findings suggest that rhLF treatment may be a
      novel therapeutic approach for prevention and treatment AR. 

PMID- 24111739
TI  - Dermatological manifestations of individuals infected with human T cell
      lymphotropic virus type I (HTLV-I).
AB  - BACKGROUND: Human T cell lymphotropic virus type I (HTLV-I) is associated with
      specific manifestations such as adult T cell lymphoma/leukemia (ATLL), HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I-associated
      uveitis, and infective dermatitis associated with HTLV-I (IDH). Although ATLL and
      IDH are considered specific manifestations of HTLV-I infection, several
      dermatological manifestations have been described in HTLV-I seropositive
      patients. OBJECTIVES: This study was conducted to determine the prevalences of
      skin lesions in patients infected with HTLV-I in an area of Brazil endemic for
      HTLV-I infection and to compare these prevalences with those in seronegative
      individuals in the same region. METHODS: A prevalence study was conducted between
      2008 and 2010 with two groups of individuals comprising, respectively, 179 HTLV-I
      seropositive (positive enzyme-linked immunosorbent assay [ELISA] and positive
      Western blot analysis) and 193 HTLV-I seronegative individuals (ELISA-negative).
      The subjects were selected on a random basis and evaluated using a questionnaire
      to obtain epidemiological and clinical data. A physical examination was performed
      to verify the presence of skin lesions. RESULTS: Superficial mycoses were found
      in 54 (30.2%) seropositive subjects and in 26 (13.5%) of the seronegative group
      (P < 0.001). Xerosis was found in 39.1% of HTLV-I infected subjects and in 9.3%
      of seronegative controls (P < 0.001). Ichthyosis was diagnosed in nine (5.0%)
      HTLV-I seropositive subjects but in none of the control group (P = 0.001). A
      diagnosis of seborrheic dermatitis was made in 43 (24.0%) HTLV-I infected
      subjects and in 24 (12.4%) seronegative controls (P = 0.004). Furthermore,
      dermatological manifestations were more intense in the HTLV-I seropositive group.
      CONCLUSIONS: Several dermatological manifestations are more common and more
      severe in HTLV-I seropositive subjects. The presence of these manifestations in
      an area endemic for HTLV-I infection may provide some clues in the investigation
      of this infection.

PMID- 24111740
TI  - Radioactive Chernobyl environment has produced high-oil flax seeds that show
      proteome alterations related to carbon metabolism during seed development.
AB  - Starting in 2007, we have grown soybean (Glycine max [L.] Merr. variety
      Soniachna) and flax (Linum usitatissimum, L. variety Kyivskyi) in the radio
      contaminated Chernobyl area and analyzed the seed proteomes. In the second
      generation flax seeds, we detected a 12% increase in oil content. To characterize
      the bases for this increase, seed development has been studied. Flax seeds were
      harvested in biological triplicate at 2, 4, and 6 weeks after flowering and at
      maturity from plants grown in nonradioactive and radio-contaminated plots in the
      Chernobyl area for two generations. Quantitative proteomic analyses based on 2-D
      gel electrophoresis (2-DE) allowed us to establish developmental profiles for 199
      2-DE spots in both plots, out of which 79 were reliably identified by tandem mass
      spectrometry. The data suggest a statistically significant increased abundance of
      proteins associated with pyruvate biosynthesis via cytoplasmic glycolysis, L
      malate decarboxylation, isocitrate dehydrogenation, and ethanol oxidation to
      acetaldehyde in early stages of seed development. This was followed by
      statistically significant increased abundance of ketoacyl-[acylcarrier protein]
      synthase I related to condensation of malonyl-ACP with elongating fatty acid
      chains. On the basis of these and previous data, we propose a preliminary model
      for plant adaptation to growth in a radio-contaminated environment. One aspect of
      the model suggests that changes in carbon assimilation and fatty acid
      biosynthesis are an integral part of plant adaptation.

PMID- 24111741
TI  - Joint analysis of additive, dominant and first-order epistatic effects of four
      genes (IGF2, MC4R, PRKAG3 and LEPR) with known effects on fat content and fat
      distribution in pigs.
AB  - LEPR, MC4R, IGF2 and PRKAG3 are genes with known effects on fat content and
      distribution in pig carcass and pork. In a study performed with Duroc *
      Landrace/Large White pigs, we have found that IGF2 has strong additive effects on
      several carcass conformational traits and on fatty acid composition in several
      anatomical locations. MC4R shows additive effects on saturated fatty acid content
      in several muscles. On the other side, almost no additive effect has been found
      for PRKAG3 and very few for LEPR. In this work, no dominant effect has been found
      for any of the four genes. Using a Bayesian Lasso approach, we have been able now
      to find first-order epistatic (mainly dominant-additive) effects between LEPR and
      PRKAG3 for intramuscular fat content and for saturated fatty acid content in L.
      dorsii, B. femoralis, Ps. major and whole ham. The presence of interactions
      between genes in the shaping of traits of such importance as intramuscular fat
      content and composition highlights the complexity of heritable traits and the
      difficulty of gene-assisted selection for such traits. 

PMID- 24111742
TI  - The risk of maternal and placental complications in pregnant women with asthma: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate if maternal asthma is associated with an increased risk
      of maternal and placental complications in pregnancy. METHODS: Electronic
      databases were searched for the following terms: (asthma or wheeze) and (pregnan*
      or perinat* or obstet*). Cohort studies published between January 1975 and March
      2012 were considered for inclusion. Forty publications met the inclusion
      criteria, reporting at least one maternal or placental complication in pregnant
      women with and without asthma. Relative risk (RR) with 95% confidence intervals
      (CIs) was calculated. RESULTS: Maternal asthma was associated with a
      significantly increased risk of cesarean section (RR = 1.31, 95%CI = [1.22
      1.39]), gestational diabetes (RR = 1.39, 95%CI = [1.17-1.66]), hemorrhage
      (antepartum: RR = 1.25, 95%CI = [1.10-1.42]; postpartum: RR = 1.29, 95%CI = [1.18
      1.41]), placenta previa (RR = 1.23, 95%CI = [1.07-1.40]), placental abruption (RR
      = 1.29, 95%CI = [1.14-1.47]) and premature rupture of membranes (RR = 1.21, 95%CI
      = 1.07-1.37). Moderate to severe asthma significantly increased the risk of
      cesarean section (RR = 1.19, 95%CI = [1.09-1.31]) and gestational diabetes (RR =
      1.19, 95%CI = [1.06-1.33]) compared to mild asthma. Bronchodilator use was
      associated with a significantly lowered risk of gestational diabetes (RR = 0.64,
      95%CI = [0.57-0.72]). CONCLUSIONS: Pregnant women with asthma are at increased
      risk of maternal and placental complications, and women with moderate/severe
      asthma may be at particular risk. Further studies are required to elucidate
      whether adequate control of asthma during pregnancy reduces these risks.

PMID- 24111743
TI  - Chemometric tools to highlight possible migration of compounds from packaging to
      sunflower oils.
AB  - Polyethylene terephthalate (PET) could be considered for the packaging of
      vegetable oils taking into account the impact of its oxygen permeability on the
      oxidation of the oil and the migration of volatile organic compounds (VOC) from
      the polymer matrix. After accelerated aging tests at 40  degrees C for 10, 20,
      and 30 days, the headspace of three sunflower oils packed in PET with high
      density polyethylene caps was carried out using solid phase microextraction. VOCs
      such as benzene hydrocarbons, ethylbenzene, xylene isomers and diethyl phthalate
      were identified in vegetable oils by gas chromatography coupled to mass
      spectrometry. Chemometric tools such as principal components analysis (PCA),
      independent components analysis (ICA), and a multiblocks analysis, common
      components and specific weight analysis (CCSWA) applied to analytical data were
      revealed to be very efficient to discriminate between samples according to oil
      oxidation products (hexanal, heptanal, 2-pentenal) and to the migration of
      packaging contaminants (xylene). 

PMID- 24111744
TI  - Induction of complete and mosaic sex-linked recessive lethal mutations by
      cigarette smoke filtrate in Drosophila melanogaster.
AB  - The genotoxic effects of cigarette smoke filtrate (SF) on the germ-line stages
      were examined in Drosophila melanogaster using the sex-linked recessive lethal
      test, which detects a broad spectrum of genetic alterations and proved to show
      correlations between mutagenicity and carcinogenicity of the tested chemicals. SF
      was extracted from fiberglass filter cartridges; each used in smoking 15
      cigarettes. The proper SF concentrations (0.2 uL) in 0.45% NaCl saline were
      injected intraperitoneally in 2- to 3-day-old wild-type males, alongside with
      controls injected with 0.2 uL of saline. The genotoxicity effects of SF were
      examined in all spermatogenesis stages of treated males. Results showed that SF
      was toxic with an median lethal dose value of approximately 0.2% and induced
      significant sterility effects. The mutagenicity of SF (0.2%) was significantly
      stage specific and induced complete sex-linked recessive lethal mutations in the
      broods representing the spermatocytes and late and early spermatogonia, and
      induced mosaic mutations in the untreated progeny in the brood representing late
      spermatogonia. These results indicated, for the first time, that SF induces
      mosaic mutations, which could result from DNA instabilities and labile
      permutations that can be replicated and passed to future generations before being
      fixed into mutations in the untreated progeny of treated males, or originating
      from mutations that result in increasing hyperplasia of the gonad that
      subsequently produce the actual mutations in later cell cycles. Such delayed
      mutagenic effects of SF indicated that SF and, consequently, cigarette smoking
      have much greater genotoxicity than what was previously predicted.

PMID- 24111745
TI  - Phenotype of htgA (mbiA), a recently evolved orphan gene of Escherichia coli and
      Shigella, completely overlapping in antisense to yaaW.
AB  - Overlapping embedded genes, such as htgA/yaaW, are assumed to be rare in
      prokaryotes. In Escherichia coli O157:H7, gfp fusions of both promoter regions
      revealed activity and transcription start sites could be determined for both
      genes. Both htgA and yaaW were inactivated strand specifically by introducing a
      stop codon. Both mutants exhibited differential phenotypes in biofilm formation
      and metabolite levels in a nontargeted analysis, suggesting that both are
      functional despite YaaW but not HtgA could be expressed. While yaaW is
      distributed all over the Gammaproteobacteria, an overlapping htgA-like sequence
      is restricted to the Escherichia-Klebsiella clade. Full-length htgA is only
      present in Escherichia and Shigella, and htgA showed evidence for purifying
      selection. Thus, htgA is an interesting case of a lineage-specific, nonessential
      and young orphan gene. 

PMID- 24111746
TI  - Regio- and stereoselective direct N-alkenylation of indoles via Pd-catalyzed
      aerobic oxidation.
AB  - With two different sets of Pd catalyst systems in hand, indoles, whether bearing
      a C3-substituent or not, can be directly alkenylated on their nitrogen atoms
      using a sterically and electronically diverse array of alkenes, in which the high
      regio- and stereoselectivity are dependent on the nature of the alkenes used.
      This process proceeds in generally good yields and is compatible with a broad
      range of functional groups. 

PMID- 24111747
TI  - Achievement emotions in elementary, middle, and high school: how do students feel
      about specific contexts in terms of settings and subject-domains?
AB  - The present work investigates students' representation of achievement emotions,
      focusing in context-specific situations in terms of settings and subject-domains,
      as a function of grade level. We involved 527 fourth-, seventh-, and eleventh
      graders, who evaluated ten discrete emotions through questionnaires, with
      reference to verbal language and mathematics, and different settings (class,
      homework, tests). Confirmatory multitrait-multimethod analyses indicated higher
      salience of subject-domains rather than settings for all the emotions; however,
      complexity of reality was best explained when also settings were accounted for.
      Analyses of variance revealed higher intensity of positive emotions for younger
      students, and the opposite pattern for older students; significant differences
      for most of the emotions based on the evaluative nature of settings, moderated by
      class levels; more intense positive emotions for mathematics and more intense
      negative emotions for Italian. Results are discussed considering their
      theoretical and applied relevance, corroborating previous literature on domain
      specificity. 

PMID- 24111748
TI  - The impact of introducing universal umbilical cord blood gas analysis and lactate
      measurement at delivery.
AB  - BACKGROUND: There is growing support for umbilical cord blood gas analysis
      (UCBGA) to be conducted at delivery. A recent study in a tertiary level obstetric
      unit found that universal UCBGA was associated with improved perinatal outcomes,
      but there is less evidence of benefit in lower-risk environments. In such
      settings, lactate analysis may be a suitable alternative. AIMS: This study
      evaluated the introduction of universal UCBGA into a secondary obstetric unit and
      universal umbilical cord lactate analysis program into primary and secondary
      units. METHODS: After education, universal UCBGA or lactate analysis was
      introduced into one primary and two secondary level obstetric units. Univariate
      and adjusted analysis assessed changes in UCBGA values and Apgar scores over the
      study period. RESULTS: There were no significant changes in mean blood gas and
      lactate values at any centre following introduction of universal UCBGA or lactate
      analysis. However, there was at the primary level obstetric unit a significant
      reduction in the proportion of neonates with moderate to severe elevations in
      umbilical artery lactate values. There was a non-significant reduction in
      arterial pH values less than 7.10 at the secondary metropolitan centre.
      CONCLUSION: The data presented in this study suggest that the benefits of
      introducing UCBGA into a tertiary obstetric centre may be reproduced in a primary
      obstetric centre within 12 months of implementation. Larger studies are required
      in secondary units to assess infrequent adverse obstetric and neonatal outcomes.

PMID- 24111749
TI  - Segmenting by risk perceptions: predicting young adults' genetic-belief profiles
      with health and opinion-leader covariates.
AB  - With a growing interest in using genetic information to motivate young adults'
      health behaviors, audience segmentation is needed for effective campaign design.
      Using latent class analysis, this study identifies segments based on young
      adults' (N = 327) beliefs about genetic threats to their health and personal
      efficacy over genetic influences on their health. A four-class model was
      identified. The model indicators fit the risk perception attitude framework
      (Rimal & Real, 2003), but the covariates (e.g., current health behaviors) did
      not. In addition, opinion leader qualities covaried with one profile: Those in
      this profile engaged in fewer preventative behaviors and more dangerous treatment
      options, and also liked to persuade others, making them a particularly salient
      group for campaign efforts. The implications for adult-onset disorders, like
      alpha-1 antitrypsin deficiency, are discussed. 

PMID- 24111750
TI  - Evaluation of two novel self-anchoring barbed sutures in a prophylactic
      laparoscopic gastropexy compared with intracorporeal tied knots.
AB  - OBJECTIVE: To compare laparoscopic gastropexy using 2 self-anchoring barbed
      sutures to gastropexy using laparoscopically tied intracorporeal knots. STUDY
      DESIGN: Prospective, randomized controlled, clinical trial. ANIMALS: Dogs (n =
      30) weighing >16 kg. METHODS: Dogs were randomly assigned to 1 of 3 laparoscopic
      gastropexy groups: group 1 (controls), intracorporeal 2-0 polydioxanone sutures
      (PDSII, Ethicon); group 2, barbed suture (0 QuillTM PDO; Angiotech); and group 3,
      barbed suture (2-0 V-LocTM 180; Covidien). Gastropexy suturing time (GST) and
      total surgery time (TST) were recorded for each dog. Complications were recorded.
      Each dog was examined by ultrasound (1, 3, and 6 months postoperatively) to
      ensure persistence of the gastropexy. One dog each in group 2 and group 3 had 2nd
      look laparoscopy to evaluate the gastropexy. RESULTS: All gastropexies were
      intact at 6 months. Mean GST was significantly longer for group 1 (36 minutes;
      range, 25-46 minutes) than for groups 2 (20 minutes; range, 16-37 minutes) and 3
      (19 minutes; range, 15-30 minutes; P < .05), which were not significantly
      different from each other. Likewise TSTs for groups 2 and 3 were significantly
      shorter than for group 1 (P < .05). CONCLUSION: Barbed sutures (QuillTM and V
      LocTM) allowed for effective intracorporeal laparoscopic suturing of an
      incisional gastropexy without tying intracorporeal knots.

PMID- 24111751
TI  - Error and its meaning in forensic science.
AB  - The discussion of "error" has gained momentum in forensic science in the wake of
      the Daubert guidelines and has intensified with the National Academy of Sciences'
      Report. Error has many different meanings, and too often, forensic practitioners
      themselves as well as the courts misunderstand scientific error and statistical
      error rates, often confusing them with practitioner error (or mistakes). Here, we
      present an overview of these concepts as they pertain to forensic science
      applications, discussing the difference between practitioner error (including
      mistakes), instrument error, statistical error, and method error. We urge
      forensic practitioners to ensure that potential sources of error and method
      limitations are understood and clearly communicated and advocate that the legal
      community be informed regarding the differences between interobserver errors,
      uncertainty, variation, and mistakes. 

PMID- 24111752
TI  - Clinical and economic burden of COPD in a medicaid population.
AB  - OBJECTIVE: To evaluate the clinical and economic burden of COPD patients to
      Medicaid. STUDY DESIGN: Retrospective, observational matched cohort design.
      METHODS: We calculated the incremental costs incurred and medical resources used
      by COPD patients relative to those without COPD. Data were obtained from 8
      Medicaid states during 2003-2007. COPD patients were defined as Medicaid
      beneficiaries >=40 years with a COPD diagnosis (ICD-9 CM: 491.xx, 492.xx, 496.xx)
      and treated with maintenance drugs for COPD. Patients were matched (1:3) to
      Medicaid beneficiaries without a COPD diagnosis on age, gender, race, index year,
      Medicare/Medicaid dual eligibility, and use of long-term care. Results were
      stratified by Medicare/Medicaid dual eligibility status and race. RESULTS: A
      total of 10,221 COPD and 30,663 non-COPD patients were included. Cohorts were on
      average 65 years of age, 80% White, and 64.8% having Medicare/Medicaid dual
      eligibility. Inpatient hospitalizations and home healthcare visits/durable
      medical equipment were primary drivers of incremental medical costs. COPD
      patients were more than twice as likely to have a hospitalization (odds ratio
      [95% confidence interval] = 2.32 [2.19, 2.45]) or home healthcare visit/durable
      medical equipment (2.95 [2.82, 3.08]) compared to non-COPD patients. Medicaid
      incurred $2118/year in incremental costs due to COPD. On average, incremental
      costs were 7 times greater for non-dual-eligible patients ($4917) compared to
      dual-eligible patients ($667), and were more than double for Blacks compared to
      Whites ($4141 vs $1593). CONCLUSION: COPD imposes a substantial economic and
      clinical burden on the Medicaid program; this burden differs by dual eligibility
      status and race.

PMID- 24111753
TI  - Evolved Quorum sensing regulator, LsrR, for altered switching functions.
AB  - In order to carry out innovative complex, multistep synthetic biology functions,
      members of a cell population often must communicate with one another to
      coordinate processes in a programmed manner. It therefore follows that native
      microbial communication systems are a conspicuous target for developing
      engineered populations and networks. Quorum sensing (QS) is a highly conserved
      mechanism of bacterial cell-cell communication and QS-based synthetic signal
      transduction pathways represent a new generation of biotechnology toolbox
      members. Specifically, the E. coli QS master regulator, LsrR, is uniquely
      positioned to actuate gene expression in response to a QS signal. In order to
      expand the use of LsrR in synthetic biology, two novel LsrR switches were
      generated through directed evolution: an "enhanced" repression and derepression
      eLsrR and a reversed repression/derepression function "activator" aLsrR. Protein
      modeling and docking studies are presented to gain insight into the QS signal
      binding to these two evolved proteins and their newly acquired functionality. We
      demonstrated the use of the aLsrR switch using a coculture system in which a QS
      signal, produced by one bacterial strain, is used to inhibit gene expression via
      aLsrR in a different strain. These first ever AI-2 controlled synthetic switches
      allow gene expression from the lsr promoter to be tuned simultaneously in two
      distinct cell populations. This work expands the tools available to create
      engineered microbial populations capable of carrying out complex functions
      necessary for the development of advanced synthetic products.

PMID- 24111755
TI  - Femtosecond photodetachment of silver anions.
AB  - The two- and three-photon detachment of negative silver ions in a femtosecond
      infrared laser field is studied using photoelectron velocity map imaging methods.
      Photoelectron angular distributions (PADs) are obtained for these detachment
      channels; these PADs change dramatically when the laser wavelength and intensity
      are changed. Theoretical predictions, which are based on the adiabatic Keldysh
      Faisal-Reiss saddle point method, are in good agreement with our experiment. The
      dependence of the PAD on the laser wavelengths and intensities is due to the
      interference between the different partial wave functions. The relative
      contributions of the different partial waves to the detachment amplitude are
      altered by changing the laser parameters and, as a result, the shape of the PAD.
      Close to the detachment threshold, the two-photon detachment process also follows
      the Wigner threshold law. Near the detachment threshold, the large differences
      between the calculated results and our experimental results indicate that the
      ponderomotive energy shifts caused by the femtosecond laser fields must be taken
      into account in the theoretical model. The three-photon detachment of Ag(-) is
      also observed and compared with theoretical calculations. 

PMID- 24111756
TI  - Unanswered questions in headache: so what is photophobia, anyway?

PMID- 24111754
TI  - Midkine as a regulator of B cell survival in health and disease.
AB  - In healthy individuals, the pool of peripheral lymphocytes is constant in size.
      The control of lymphoid homeostasis is the result of a very fine balance between
      lymphocyte production, survival and proliferation. Survival factors have been
      shown to play a critical role in maintaining the correct size of lymphocyte
      populations. Midkine, a heparin-binding cytokine was recently shown to be
      involved in cell proliferation, differentiation and apoptosis in various cell
      types including normal and malignant B cells. This review focuses on the role of
      midkine in the regulation of peripheral B cell survival in health and disease.
      LINKED ARTICLES: This article is part of a themed section on Midkine. To view the
      other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue
      4.

PMID- 24111757
TI  - Glycemic control and prevention of surgical site infection.
AB  - BACKGROUND: Stress hyperglycemia is associated with increased risk of surgical
      site infections (SSIs). Use of strict or tight glycemic control with intensive
      insulin therapy to prevent SSIs is controversial. METHODS: Review of pertinent
      English-language literature. RESULTS: There is a large body of literature
      supporting an association between stress hyperglycemia and SSIs. The quality of
      evidence from randomized controlled trials and meta-analyses that strict glycemic
      control reduces SSIs or any infections is low, and the strength of recommendation
      for strict glycemic control is weak due to the associated increase in moderate
      and severe hypoglycemia. CONCLUSION: Current recommendations for glycemic control
      in surgical patients are informed primarily by trials using intensive insulin
      therapy in critically ill patients. Further research is necessary to ascertain
      the optimal glycemic target for non-critically ill patients, to determine if
      subsets of patients may benefit from strict glycemic control, and to identify
      alternative methods for treating stress hyperglycemia and explaining the
      mechanisms by which it increases infectious risk.

PMID- 24111758
TI  - Clostridium difficile bacteremia.

PMID- 24111760
TI  - Cardiac metastasis of a low-grade myofibroblastic sarcoma.
AB  - We aim to present a rare case of low-grade myofibroblastic sarcoma arising in the
      inguinal region accompanied by cardiac metastasis. A 36-year-old male patient
      suffering from recurrent inguinal swelling was operated on and the initial
      histopathological evaluation mistakenly diagnosed the condition as benign. During
      follow-up, a recurrence of mass was detected in the same region and a
      pathological examination revealed a low-grade myofibroblastic sarcoma. Cardiac
      metastasis was diagnosed shortly before rapid disease progression and death. The
      learning points relevant to this case are as follows: (1) Echocardiographic
      screening in patients with noncardiac myofibroblastic sarcomas may be helpful in
      the detection of silent metastasis. (2) Low-grade myofibroblastic sarcomas in the
      inguinal region may be misdiagnosed as benign after enucleation. Thus, rigorous
      histopathological examination of myofibroblastic sarcomas is crucial. (3)
      According to our knowledge, this is the first report of a low-grade
      myofibroblastic sarcoma to have a potential for cardiac metastasis with
      potentially fatal course. 

PMID- 24111761
TI  - Bridging the cybernetic divide.

PMID- 24111759
TI  - Distinct splice variants and pathway enrichment in the cell-line models of
      aggressive human breast cancer subtypes.
AB  - This study was conducted as a part of the Chromosome-Centric Human Proteome
      Project (C-HPP) of the Human Proteome Organization. The United States team of C
      HPP is focused on characterizing the protein-coding genes in chromosome 17.
      Despite its small size, chromosome 17 is rich in protein-coding genes; it
      contains many cancer-associated genes, including BRCA1, ERBB2, (Her2/neu), and
      TP53. The goal of this study was to examine the splice variants expressed in
      three ERBB2 expressed breast cancer cell-line models of hormone-receptor-negative
      breast cancers by integrating RNA-Seq and proteomic mass spectrometry data. The
      cell lines represent distinct phenotypic variations subtype: SKBR3 (ERBB2+
      (overexpression)/ER-/PR-; adenocarcinoma), SUM190 (ERBB2+ (overexpression)/ER-/PR
      ; inflammatory breast cancer), and SUM149 (ERBB2 (low expression) ER-/PR-;
      inflammatory breast cancer). We identified more than one splice variant for 1167
      genes expressed in at least one of the three cancer cell lines. We found multiple
      variants of genes that are in the signaling pathways downstream of ERBB2 along
      with variants specific to one cancer cell line compared with the other two cancer
      cell lines and with normal mammary cells. The overall transcript profiles based
      on read counts indicated more similarities between SKBR3 and SUM190. The top
      ranking Gene Ontology and BioCarta pathways for the cell-line specific variants
      pointed to distinct key mechanisms including: amino sugar metabolism, caspase
      activity, and endocytosis in SKBR3; different aspects of metabolism, especially
      of lipids in SUM190; cell-to-cell adhesion, integrin, and ERK1/ERK2 signaling;
      and translational control in SUM149. The analyses indicated an enrichment in the
      electron transport chain processes in the ERBB2 overexpressed cell line models
      and an association of nucleotide binding, RNA splicing, and translation processes
      with the IBC models, SUM190 and SUM149. Detailed experimental studies on the
      distinct variants identified from each of these three breast cancer cell line
      models that may open opportunities for drug target discovery and help unveil
      their specific roles in cancer progression and metastasis. 

PMID- 24111763
TI  - A roundtable discussion: understanding medical devices and users in context.

PMID- 24111764
TI  - A unique perspective: Q&A with a clinician/vendor on EHR usability.

PMID- 24111765
TI  - Visual, perceptual, and cognitive factors in human-computer interface design and
      use.

PMID- 24111766
TI  - Applying human factors engineering: naturally safe software-user interfaces.

PMID- 24111767
TI  - How can we eliminate error when we have no consistency?

PMID- 24111768
TI  - The business case: selling the value of HFE in medical device IT design.

PMID- 24111770
TI  - Lessons from another industry: aviation, usability, and medical device design.

PMID- 24111771
TI  - A review: healthcare usability evaluation methods.

PMID- 24111772
TI  - The intersection of IT and human factors: summative testing in safety-enhanced
      EHR design.

PMID- 24111773
TI  - Human factors and medical IT systems: complex incident reporting systems and
      multiple IV infusions.

PMID- 24111774
TI  - Operative heuristics: optimizing perioperative status boards.

PMID- 24111775
TI  - Impact of a computerized system on resident sign-out.

PMID- 24111777
TI  - Gill worm Ancyrocephalus percae (Ergens 1966) outbreak negatively impacts the
      Eurasian perch Perca fluviatilis L. stock of Lake Constance, Germany.

PMID- 24111778
TI  - Bmp4 regulates chick Ebf2 and Ebf3 gene expression in somite development.
AB  - The chick Early B-cell Factor-2 and 3 (cEbf2 and cEbf3) genes are members of EBF
      family of helix loop helix transcription factors. The expression, regulation and
      importance of these genes have been extensively studied in lymphatic, nervous and
      muscular tissues. Recently, a new role for some members of EBF in bone
      development has been investigated. However, the expression profile and regulation
      in the axial skeleton precursor, the somite, have yet to be elucidated.
      Therefore, this study was aimed to investigate the expression and regulation of
      cEbf2 and cEbf3 genes in the developing chick embryo somite from HH4 to HH28. The
      spatiotemporal expression study revealed predominant localization of cEbf2 and
      cEbf3 in the lateral sclerotomal domains and later around vertebral cartilage
      anlagen of the arch and the proximal rib. Subsequently, microsurgeries, ectopic
      gene expression experiments were performed to analyze which tissues and factors
      regulate cEbf2 and cEbf3 expression. Lateral barriers experiments indicated the
      necessity for lateral signal(s) in the regulation of cEbf2 and cEbf3 genes.
      Results from tissue manipulations and ectopic gene expression experiments
      indicate that lateral plate-derived Bmp4 signals are necessary for the initiation
      and maintenance of cEbf2 and cEbf3 genes in somites. In conclusion, cEbf2 and
      cEbf3 genes are considered as lateral sclerotome markers which their expression
      is regulated by Bmp4 signals from the lateral plate mesoderm. 

PMID- 24111779
TI  - Assessment of the exposure of workers to the insecticide imidacloprid during
      application on various field crops by a hand-held power sprayer.
AB  - Exposure assessment and risk assessment for imidacloprid were conducted for
      agricultural workers through mixing/loading and application with a power sprayer
      in four kinds of crop fields. The spray suspension was prepared with 10% wettable
      powder (250 g) for 5 min and applied on field crops for 1 h. A patch method and a
      personal air sampler with XAD-2 resin were used to monitor the dermal and
      inhalation exposure, respectively. In mixing/loading, the total dermal exposure
      on the whole body was 0.2 (cucumber) to 2.0 (apple) mg and the most exposed part
      of body was the hand (48-100% of total exposure). During the application of
      imidacloprid, whole dermal exposure was in the range of 2.9 (apple) to 9.5 (green
      pepper) mg. The primary sites exposed to pesticides were legs (51-79% of total
      exposure) in cucumber, green pepper, and paddy fields, whereas the primary sites
      were hands (35% of total exposure) in the apple field. The inhalation exposure
      was determined to be 0.2 (paddy) to 2.8 (cucumber) MUg and 0.2 (paddy) to 3.0
      (cucumber) MUg during mixing/loading and application, respectively. The
      absorbable quantity of exposure and the margin of safety were determined for risk
      assessment. Workers were exposed through inhalation as 23-93 and 2-11% of the
      absorbable quantity of exposure during mixing and application, respectively. The
      margin of safety of all cases was much higher than 1, indicating the lowest
      possibility of risk. 

PMID- 24111780
TI  - Improving waste management strategies for small livestock farms.

PMID- 24111776
TI  - HypoxamiRs and cancer: from biology to targeted therapy.
AB  - SIGNIFICANCE: Hypoxia is a hallmark of the tumor microenvironment and represents
      a major source of failure in cancer therapy. RECENT ADVANCES: Recent work has
      generated extensive evidence that microRNAs (miRNAs) are significant components
      of the adaptive response to low oxygen in tumors. Induction of specific miRNAs,
      collectively termed hypoxamiRs, has become an accepted feature of the hypoxic
      response in normal and transformed cells. CRITICAL ISSUES: Overexpression of miR
      210, the prototypical hypoxamiR, is detected in most solid tumors, and it has
      been linked to adverse prognosis in many tumor types. Several miR-210 target
      genes, including iron-sulfur (Fe-S) cluster scaffold protein (ISCU) and glycerol
      3-phosphate dehydrogenase 1-like (GPD1L), have been correlated with prognosis in
      an inverse fashion to miR-210, suggesting that their down- regulation by miR-210
      occurs in vivo and contributes to tumor growth. Additional miRNAs are modulated
      by decreased oxygen tension in a more tissue-specific fashion, adding another
      level of complexity over the classic hypoxia-regulated gene network. FUTURE
      DIRECTIONS: From a biological standpoint, hypoxamiRs are emerging modifiers of
      cancer cell response to the adaptive challenges of the microenvironment. From a
      clinical perspective, assessing the status of these miRNAs may contribute to a
      detailed understanding of hypoxia-induced mechanisms of resistance and/or to the
      fine-tuning of future hypoxia-modifying therapies.

PMID- 24111781
TI  - DNA gold nanoparticle nanocomposite films for chemiresistive vapor sensing.
AB  - Chemiresistive vapor sensors combining functionalized gold nanoparticles and
      single-stranded DNA oligomers are investigated to enhance specificity in chemical
      sensing. Sensors are made by depositing DNA-functionalized gold nanoparticles
      onto microfabricated electrodes using four distinct sequences. Sensor performance
      is evaluated for response to relative humidity and exposure to vapor analytes
      including ethanol, methanol, hexane, dimethyl methylphosphonate, and toluene
      under different relative humidity. It is found that sensors display a
      nonmonotonic resistance change toward increasing humidity due to the combined
      effects of hydration induced swelling and ionic conduction. Responses to vapor
      analytes show sequence-dependent patterns as well as a strong influence of
      humidity. Overall, the findings are encouraging for using DNA oligomers to
      enhance specificity in chemical sensing. 

PMID- 24111782
TI  - Disparities in symptom burden and renal transplant eligibility: a pilot study.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) on hemodialysis (HD)
      suffer from a high symptom burden. However, there is significant heterogeneity
      within the HD population; certain subgroups, such as the elderly, may experience
      disproportionate symptom burden. OBJECTIVES: The study's objective was to propose
      a category of HD patients at elevated risk for symptom burden (those patients who
      are not transplant candidates) and to compare symptomatology among transplant
      ineligible versus eligible HD patients. DESIGN: This was a cross-sectional study.
      SETTING/SUBJECTS: English-speaking, cognitively intact patients receiving HD and
      who were either transplant eligible (n=25) or ineligible (n=32) were recruited
      from two urban HD units serving patients in the greater New York City region.
      MEASUREMENTS: In-person interviews were conducted to ascertain participants'
      symptom burden using the Dialysis Symptom Index (DSI), perceived symptom bother
      and attribution (whether the symptom was perceived to be related to HD
      treatment), and quality of life using the SF-36. Participants' medical records
      were reviewed to collect demographic and clinical data. RESULTS: Transplant
      ineligible (versus eligible) patients reported an average of 13.9+/-4.6 symptoms
      versus 9.2+/-4.4 symptoms (p<0.01); these differences persisted after adjustment
      for multiple factors. A greater proportion of transplant ineligible (versus
      eligible) patients attributed their symptoms to HD and were more likely to report
      greater bother on account of the symptoms. Quality of life was also significantly
      lower in the transplant ineligible group. CONCLUSIONS: Among HD patients,
      transplant eligibility is associated with symptom burden. Our pilot data suggest
      that consideration be given to employing transplant status as a method of
      identifying HD patients at risk for greater symptom burden and targeting them for
      palliative interventions.

PMID- 24111784
TI  - In vitro evaluation of the cytotoxic and apoptogenic properties of aloe whole
      leaf and gel materials.
AB  - Aloe gel and whole-leaf materials have shown biological effects with potential
      therapeutic applications, and recently, their drug-absorption enhancement
      properties have been discovered. It is important to establish a safety profile
      for these materials before they can be used in pharmaceutical products. The aim
      of the study was to investigate the in vitro cytotoxicity of Aloe vera, Aloe
      marlothii, Aloe speciosa and Aloe ferox against human hepatocellular (HepG2),
      human neuroblastoma cells (SH-SY5Y) and human adenocarcinoma epithelial cells
      (HeLa). Flow cytometry was used to measure cell viability, apoptosis and reactive
      oxygen species (ROS). The aloe gel materials investigated only decreased cell
      viability at concentrations of >10 mg/mL and exhibited half-maximal cytotoxic
      concentration (CC(50)) values above 1000 mg/mL, except for A. vera gel in HepG2
      cells (CC(50) = 269.3 mg/mL). A. speciosa whole-leaf material showed a
      significant decrease in viability of Hela cells, whereas the other whole-leaf
      materials did not show a similar effect. The aloe gel materials in general showed
      low levels of apoptosis, whereas A. vera and A. speciosa whole-leaf materials
      caused a dose-dependent increase of apoptosis in HeLa cells. None of the aloe
      materials investigated exhibited a significant increase in ROS. It can be
      concluded that the selected aloe materials caused only limited reduction in cell
      viability with limited in vitro cytotoxicity effects. Further, neither
      significant apoptosis effects were observed nor induction of ROS.

PMID- 24111783
TI  - Efficacy and longevity of newly developed catnip oil microcapsules against stable
      fly oviposition and larval growth.
AB  - The stable fly, Stomoxys calcitrans (Diptera: Muscidae), is one of the most
      important pests of cattle and costs U.S. cattle producers billions of dollars in
      losses annually. In this study, the efficacy of catnip oil encapsulated in
      gelatin in oviposition deterrence and larval growth inhibition in stable flies
      was examined under laboratory conditions. More than 98% inhibition of stable fly
      larval growth and female oviposition was observed in larval and oviposition media
      treated with encapsulated catnip oil (0.5 g). Further, dose-response tests showed
      that as little as 0.1 g of encapsulated catnip oil provided > 85% oviposition
      deterrence. The release of nepetalactones from the capsules was more rapid when
      the capsules were placed on a moist substrate rather than a dry substrate.
      Encapsulated catnip oil also exhibited antibacterial activity, supporting the
      hypothesis that its inhibition of larval growth may be based on its killing of
      the bacteria on which larvae feed. The use of encapsulated catnip oil can provide
      an alternative control strategy for stable fly management.

PMID- 24111785
TI  - External quality assessment in molecular immunohematology: the INSTAND
      proficiency test program.
AB  - BACKGROUND: Genotyping for red blood cell (RBC), platelet (PLT), and granulocyte
      antigens is a new tool for clinical pathology, transfusion medicine services, and
      blood banks. Proficiency in laboratory tests can be established by external
      quality assessments (EQAs), which are required for clinical application in many
      health care systems. There are few EQAs for molecular immunohematology. STUDY
      DESIGN AND METHODS: We analyzed the participation and pass rates in an EQA for
      RBC, PLT, and granulocyte antigens. This EQA was distributed by INSTAND, a large
      nonprofit provider of proficiency tests, twice per year since Fall 2006 as EQA
      Number 235 Immunohematology A (molecular diagnostic). The coordinators defined at
      the outset which alleles are mandatory for detection. RESULTS: The number of
      participants steadily increased from 51 to 73 per proficiency by Fall 2012. More
      than 60 institutions utilized this EQA at least once a year. Approximately 80% of
      them participated in RBC, 68% in PLT, and 22% in granulocyte systems. With the
      exceptions of RHD (82%) and granulocytes (85%), pass rates exceeded 93%. While
      the pass rate increased for granulocyte and decreased for the ABO system, the
      pass rates for the other systems changed little over 61/2 years. CONCLUSIONS: The
      INSTAND proficiency test program was regularly used for EQA by many institutions,
      particularly in Central Europe. While the technical standards and pass rates in
      the participating laboratories were high, there has been little improvement in
      pass rates since 2006.

PMID- 24111786
TI  - Amino acid residues involved in inactivation of the Escherichia coli multidrug
      resistance repressor MarR by salicylate, 2,4-dinitrophenol, and plumbagin.
AB  - MarR is the dedicated autorepressor of the marRAB operon found in seven genera of
      the Enterobacteraceae. The MarA transcriptional regulator directly activates
      numerous genes involved in multidrug resistance and other environmental
      responses. MarR is inactivated by certain phenolic ligands, such as salicylate,
      by an unknown mechanism. Our recent work has shown that several amino acid
      residues of Escherichia coli MarR affecting ligand binding are located between
      the dimerization and DNA-binding domains. To further characterize the ligand
      binding region of MarR, we have now examined 7 point mutants generated by random
      mutagenesis and 11 site-directed alanine replacement mutants for inactivation by
      three ligands: salicylate, 2,4-dinitrophenol, and plumbagin. Inactivation of MarR
      was quantitated in intact cells by loss of MarR-mediated repression of a
      chromosomal mar-lacZ transcriptional fusion. The results showed that most of the
      residues important for ligand effectiveness lay in the alpha1 and alpha2 helices
      of MarR, between the putative DNA-binding domain and the dimerization domain of
      MarR, reinforcing our earlier findings. Moreover, the three ligands had
      different, but overlapping, sets of residues impacting their effects on MarR. 

PMID- 24111787
TI  - Future therapies for pre-eclampsia: beyond treading water.
AB  - Pre-eclampsia remains a major burden of disease, accounting for approximately
      50,000-70,000 maternal deaths each year worldwide. Frustratingly, the management
      of pre-eclampsia has remained essentially unchanged for much of the last century
      and focussed primarily on maternal blood pressure control to allow fetal
      maturation. Recent advances in the understanding of the pathogenesis of pre
      eclampsia and the elucidation of distinct underlying mechanisms offer the genuine
      prospect of new and effective therapies that may transform outcomes for millions
      of women and their babies. 

PMID- 24111788
TI  - Pistillate flowers experience more pollen limitation and less geitonogamy than
      perfect flowers in a gynomonoecious herb.
AB  - Gynomonoecy, a sexual system in which plants have both pistillate (female)
      flowers and perfect (hermaphroditic) flowers, occurs in at least 15 families, but
      the differential reproductive strategies of the two flower morphs within one
      individual remain unclear. Racemes of Eremurus anisopterus (Xanthorrhoeaceae)
      have basal pistillate and distal perfect flowers. To compare sex allocation and
      reproductive success between the two flower morphs, we measured floral traits,
      pollinator preferences, and pollen movement in the field. Pollen limitation was
      more severe in pistillate flowers; bee pollinators preferred to visit perfect
      flowers, which were also capable of partial self-fertilization. Pollen-staining
      experiments indicated that perfect flowers received a higher proportion of intra
      plant pollen (geitonogamy) than pistillate flowers. Plants with greater numbers
      of pistillate flowers received more outcross pollen. The differential
      reproductive success conformed with differential floral sex allocation, in which
      pistillate flowers produce fewer but larger ovules, resulting in outcrossed
      seeds. Our flower manipulations in these nectarless gynomonoecious plants
      demonstrated that perfect flowers promote seed quantity in that they are more
      attractive to pollinators, while pistillate flowers compensate for the loss of
      male function through better seed quality. These results are consistent with the
      outcrossing-benefit hypothesis for gynomonoecy. 

PMID- 24111789
TI  - TTF-1 expression in breast carcinoma: an unusual but real phenomenon.
AB  - AIMS: To evaluate thyroid transcription factor-1 (TTF-1) expression in a large
      cohort of invasive breast carcinomas (IBCs) using two commercially available
      monoclonal antibody clones (8G7G3/1 and SPT24). METHODS AND RESULTS: Nuclear and
      cytoplasmic TTF-1 expression was evaluated in 1132 primary IBCs and 208 primary
      pulmonary carcinomas using tissue microarray (TMA) sections. TTF-1 nuclear
      expression was detected in one of 1132 (0.09%) IBCs by 8G7G3/1. In pulmonary
      carcinoma, TTF-1 expression was detected in 149 (71.6%) and 147 (70.6%) cases by
      8G7G3/1 and SPT24, respectively, with no significant difference being seen
      between the two clones (P = 0.839), and there was good consistency between these
      two antibodies in differentiating breast and pulmonary carcinomas (kappa value
      0.905; P < 0.001). Both clones showed high specificity but relatively low
      sensitivity. Cytoplasmic TTF-1 expression was detected in 44 IBCs by 8G7G3/1, and
      this particular expression pattern was an independent adverse prognostic factor.
      CONCLUSIONS: Both TTF-1 antibodies (clones 8G7G3/1 and SPT24) were useful in
      differentiating breast from pulmonary carcinomas. Nuclear expression of TTF-1 was
      detected in IBCs by 8G7G3/1, but not by SPT24. Cytoplasmic expression of 8G7G3/1
      was seen in IBC for the first time, and was an independent unfavourable
      prognostic factor.

PMID- 24111790
TI  - Automated image mosaics by non-automated light microscopes: the MicroMos software
      tool.
AB  - Light widefield microscopes and digital imaging are the basis for most of the
      analyses performed in every biological laboratory. In particular, the
      microscope's user is typically interested in acquiring high-detailed images for
      analysing observed cells and tissues, meanwhile being representative of a wide
      area to have reliable statistics. The microscopist has to choose between higher
      magnification factor and extension of the observed area, due to the finite size
      of the camera's field of view. To overcome the need of arrangement, mosaicing
      techniques have been developed in the past decades for increasing the camera's
      field of view by stitching together more images. Nevertheless, these approaches
      typically work in batch mode and rely on motorized microscopes. Or alternatively,
      the methods are conceived just to provide visually pleasant mosaics not suitable
      for quantitative analyses. This work presents a tool for building mosaics of
      images acquired with nonautomated light microscopes. The method proposed is based
      on visual information only and the mosaics are built by incrementally stitching
      couples of images, making the approach available also for online applications.
      Seams in the stitching regions as well as tonal inhomogeneities are corrected by
      compensating the vignetting effect. In the experiments performed, we tested
      different registration approaches, confirming that the translation model is not
      always the best, despite the fact that the motion of the sample holder of the
      microscope is apparently translational and typically considered as such. The
      method's implementation is freely distributed as an open source tool called
      MicroMos. Its usability makes building mosaics of microscope images at subpixel
      accuracy easier. Furthermore, optional parameters for building mosaics according
      to different strategies make MicroMos an easy and reliable tool to compare
      different registration approaches, warping models and tonal corrections. 

PMID- 24111792
TI  - Carbothermal reduction of Ti-modified IRMOF-3: an adaptable synthetic method to
      support catalytic nanoparticles on carbon.
AB  - This work describes a novel method for the preparation of titanium oxide
      nanoparticles supported on amorphous carbon with nanoporosity (Ti/NC) via the
      post-synthetic modification of a Zn-based MOF with an amine functionality, IRMOF
      3, with titanium isopropoxide followed by its carbothermal pyrolysis. This
      material exhibited high purity, high surface area (>1000 m(2)/g), and a high
      dispersion of metal oxide nanoparticles while maintaining a small particle size
      (~4 nm). The material was shown to be a promising catalyst for oxidative
      desulfurization of diesel using dibenzothiophene as a model compound as it
      exhibited enhanced catalytic activity as compared with titanium oxide supported
      on activated carbon via the conventional incipient wetness impregnation method.
      The formation mechanism of Ti/NC was also proposed based on results obtained when
      the carbothermal reduction temperature was varied.

PMID- 24111793
TI  - Assessing the effectiveness of the COPD Assessment Test (CAT) to evaluate COPD
      severity and exacerbation rates.
AB  - AIMS: The CAT is a short, simple eight-item questionnaire for assessing and
      monitoring COPD. It is not known how reliable the CAT scores are for COPD
      patients who are frequently exacerbated. The effectiveness of the CAT for
      assessing COPD severity and exacerbation rates was evaluated. METHODS: This study
      enrolled 165 stable COPD patients who completed the CAT between April 2011 and
      February 2012. RESULTS: Patients had a mean forced expiratory volume in one
      second (FEV1) equal to 43.7% of the predicted value and a mean CAT score of 21.2
      (+/- 7.56) units. There was a good association between the FEV1 (percentage of
      predicted value) and CAT scores (p < 0.0001). Frequent exacerbators had
      significantly higher CAT scores than infrequent exacerbators (24.8 +/- 6.7 versus
      17.5 +/- 6.5, p < 0.0001). Also, as the frequency of the COPD exacerbations
      increased, CAT scores (p < 0.0001) significantly increased. There was a
      significant association between the frequency of hospitalization and the CAT
      scores (p = 0.001). CONCLUSIONS: We observed a good relation between the CAT, FEV
      1, and disease severity in patients with COPD. We found that the baseline CAT
      scores are elevated in frequent exacerbators.

PMID- 24111791
TI  - Engendering biased signalling from the calcium-sensing receptor for the
      pharmacotherapy of diverse disorders.
AB  - The human calcium-sensing receptor (CaSR) is widely expressed in the body, where
      its activity is regulated by multiple orthosteric and endogenous allosteric
      ligands. Each ligand stabilizes a unique subset of conformational states, which
      enables the CaSR to couple to distinct intracellular signalling pathways
      depending on the extracellular milieu in which it is bathed. Differential
      signalling arising from distinct receptor conformations favoured by each ligand
      is referred to as biased signalling. The outcome of CaSR activation also depends
      on the cell type in which it is expressed. Thus, the same ligand may activate
      diverse pathways in distinct cell types. Given that the CaSR is implicated in
      numerous physiological and pathophysiological processes, it is an ideal target
      for biased ligands that could be rationally designed to selectively regulate
      desired signalling pathways in preferred cell types.

PMID- 24111796
TI  - Long term outcome after surgical correction of mandibular brachygnathia with
      unilateral type 1 external skeletal fixation.
AB  - OBJECTIVE: To describe complications and long-term outcome after surgical
      correction of severe overbite in 7 horses using corrective osteotomy and a Type I
      external fixator. STUDY DESIGN: Case series. ANIMALS: Horses (n = 7). METHODS:
      Seven horses with severe mandibular brachygnathia were treated by corrective
      osteotomy and a Type I external fixator. Data on surgical technique,
      complications, long-term outcome and owner satisfaction were recorded. RESULTS:
      Severe mandibular brachygnathia was corrected successfully in all horses. Short
      term follow-up revealed a relatively high morbidity due to several complications
      such as surgical site infection, sequestrum formation and instability due to
      early pin loosening. Long-term over all owner satisfaction was very high.
      CONCLUSIONS: Corrective osteotomy and fixation with an external fixator is an
      effective surgical technique for correction of severe mandibular brachygnathia
      and offers good results in a long-term perspective.

PMID- 24111797
TI  - Disease resistance and immune-relevant gene expression in golden mandarin fish,
      Siniperca scherzeri Steindachner, infected with infectious spleen and kidney
      necrosis virus-like agent.
AB  - Infectious spleen and kidney necrosis virus (ISKNV), family Iridoviridae, genus
      Megalocytivirus, may cause high mortality rates such as those seen in mandarin
      fish, Siniperca chuatsi. ISKNV has attracted much attention due to the possible
      environmental threat and economic losses it poses on both cultured and wild
      populations. We have investigated the pathogenicity of ISKNV-like agent
      Megalocytivirus, isolated from infected pearl gourami, in golden mandarin fish,
      Siniperca scherzeri - a member of the Percichthyidae family - and in another
      Percichthyidae species, S. chuatsi. Fish were challenged with four different
      doses of ISKNV-like agent Megalocytivirus (1, 10, 100 or 1000 MUg per fish) over
      a 30-day period, and cumulative fish mortalities were calculated for each group.
      No significant mortality was observed for fish challenged with the lowest dose (1
      MUg per fish) relative to a control group. However, all other challenged groups
      showed 100% mortality over a 30-day period in proportion to the challenge dose.
      Quantitative real-time PCR was performed to measure mRNA expression levels for
      six immune-related genes in golden mandarin fish following ISKNV-like agent
      challenge. mRNA expression levels for IRF1, Mx, viperin and interleukin 8
      significantly increased, while mRNA levels for IRF2 and IRF7 remained constant or
      declined during the challenge period. 

PMID- 24111795
TI  - Hypoxamirs and mitochondrial metabolism.
AB  - SIGNIFICANCE: Chronic hypoxia can drive maladaptive responses in numerous organ
      systems, leading to a multitude of chronic mammalian diseases. Oxygen homeostasis
      is intimately linked with mitochondrial metabolism, and dysfunction in these
      systems can combine to form the backbone of hypoxic-ischemic injury in multiple
      tissue beds. Increased appreciation of the crucial roles of hypoxia-associated
      miRNA (hypoxamirs) in metabolism adds a new dimension to our understanding of the
      regulation of hypoxia-induced disease. RECENT ADVANCES: Myriad factors related to
      glycolysis (e.g., aldolase A and hexokinase II), tricarboxylic acid cycle
      function (e.g., glutaminase and iron-sulfur cluster assembly protein 1/2), and
      apoptosis (e.g., p53) have been recently implicated as targets of hypoxamirs. In
      addition, several hypoxamirs have been implicated in the regulation of the master
      transcription factor of hypoxia, hypoxia-inducible factor-1alpha, clarifying how
      the cellular program of hypoxia is sustained and resolved. CRITICAL ISSUES:
      Central to the discussion of metabolic change in hypoxia is the Warburg effect, a
      shift toward anaerobic metabolism that persists after normal oxygen levels have
      been restored. Many newly discovered targets of hypoxia-driven microRNA converge
      on pathways known to be involved in this pathological phenomenon and the
      apoptosis-resistant phenotype associated with it. FUTURE DIRECTIONS: The often
      synergistic functions of miRNA may make them ideal therapeutic targets. The use
      of antisense inhibitors is currently being considered in diseases in which
      hypoxia and metabolic dysregulation predominate. In addition, exploration of
      pleiotripic miRNA functions will likely continue to offer unique insights into
      the mechanistic relationships of their downstream target pathways and associated
      hypoxic phenotypes.

PMID- 24111798
TI  - Unanswered questions in headache: so what is photophobia, anyway?

PMID- 24111799
TI  - Heart failure following creation of an arteriovenous fistula for hemodialysis.
AB  - Careful analysis of the Doppler profile, performance of maneuvers during image
      acquisition, and comparison of data with prior studies are basic tools that allow
      us to provide useful clinical information and improved diagnostic accuracy. Here,
      we discuss a patient in whom a thorough evaluation of the Doppler pattern at rest
      and during maneuvers and the identification of temporal changes in cardiac
      hemodynamics helped establish a diagnosis. 

PMID- 24111800
TI  - Lithographically defined macroscale modulation of lateral fluidity and phase
      separation realized via patterned nanoporous silica-supported phospholipid
      bilayers.
AB  - Using lithographically defined surfaces consisting of hydrophilic patterns of
      nanoporous and nonporous (bulk) amorphous silica, we show that fusion of small,
      unilamellar lipid vesicles produces a single, contiguous, fluid bilayer phase
      experiencing a predetermined pattern of interfacial interactions. Although long
      range lateral fluidity of the bilayer, characterized by fluorescence recovery
      after photobleaching, indicates a nominally single average diffusion constant,
      fluorescence microscopy-based measurements of temperature-dependent onset of
      fluidity reveals a locally enhanced fluidity for bilayer regions supported on
      nanoporous silica in the vicinity of the fluid-gel transition temperature.
      Furthermore, thermally quenching lipid bilayers composed of a binary lipid
      mixture below its apparent miscibility transition temperature induces
      qualitatively different lateral phase separation in each region of the supported
      bilayer: The nanoporous substrate produces large, microscopic domains (and domain
      aggregates), whereas surface texture characterized by much smaller domains and
      devoid of any domain-aggregates appears on bulk glass-supported regions of the
      single-lipid bilayer. Interestingly, lateral distribution of the constituent
      molecules also reveals an enrichment of gel-phase lipids over nanoporous regions,
      presumably as a consequence of differential mobilities of constituent lipids
      across the topographic bulk/nanoporous boundary. Together, these results reveal
      that subtle local variations in constraints imposed at the bilayer interface,
      such as by spatial variations in roughness and substrate adhesion, can give rise
      to significant differences in macroscale biophysical properties of phospholipid
      bilayers even within a single, contiguous phase. 

PMID- 24111801
TI  - Synthesis of fungal glycolipid asperamide B and investigation of its ability to
      stimulate natural killer T cells.
AB  - The relationship between mold and asthma has been recognized for decades, but the
      molecular triggers of asthma generated by molds have not been fully elucidated. A
      glycolipid generated by Aspergillus species has recently been identified that
      triggers airway hyperreactivity via natural killer T cell activation. The
      synthesis of this glycolipid and structural variants designed to allow
      identification of the features of this glycolipid required for recognition by
      natural killer T cells is described. 

PMID- 24111802
TI  - Occurrence and distribution of endosulfan in water, sediment, and fish tissue: an
      ecological assessment of protected lands in south Florida.
AB  - Over the past 30 years, endosulfan, one of the last polychlorinated pesticides
      still in use, has received considerable attention and has been the subject of a
      number of international regulations and restriction action plans worldwide. This
      study aimed to monitor the presence and to assess the potential transport of
      endosulfan within the protected areas of Everglades National Park, Biscayne
      National Park, and Big Cypress National Preserve, South Florida, USA. Endosulfan
      sulfate was the major metabolite detected in all matrices in areas along the C
      111 and C-111E canals, which drain the Homestead agricultural area and discharge
      to either Florida or Biscayne Bays, both of which are critical wildlife habitats.
      Endosulfan concentrations of up to 158 ng L(-1) and 57 ng g(-1) were observed in
      surface water and sediments, respectively, which exceeded the U.S. EPA's chronic
      water quality criteria (56 ng L(-1)). Elevated levels of up to 371 ng g(-1) of
      endosulfan sulfate were detected in whole fish tissue. 

PMID- 24111803
TI  - Meta-analysis of deep-sequenced fungal communities indicates limited taxon
      sharing between studies and the presence of biogeographic patterns.
AB  - High-throughput amplicon sequencing gives new insights into fungal community
      ecology. Massively generated molecular data lead to the discovery of vast fungal
      diversity. However, it is unclear to what extent operational taxonomic units
      (OTUs) overlap among independent studies, because no comparative studies exist.
      We compared fungal diversity based on the internal transcribed spacer (ITS1)
      region among 10 published studies. Starting from the raw 454 pyrosequencing data,
      we used a uniform pipeline to prune the reads. We investigated fungal richness
      and taxonomic composition among phyllosphere and soil fungal communities, as well
      as biogeographic signals in the data. We did not find globally distributed OTUs,
      even when comparing fungal communities from similar habitats (phyllosphere or
      soil). This suggests that high local fungal diversity scales up to high global
      diversity. The most OTU-rich classes in the phyllosphere were Dothideomycetes
      (21%) and Sordariomycetes (14%), and in the soil were Sordariomycetes (13%) and
      Agaricomycetes (12%). The richness estimates suggest the presence of undiscovered
      fungal diversity even in deeply sequenced study systems. The small number of OTUs
      shared among studies indicates that globally distributed taxa and habitat
      generalists may be rare. Latitudinal diversity decline and distance decay
      relationships suggest the presence of biogeographic patterns similar to those in
      plants and animals. 

PMID- 24111804
TI  - The question of aborted-fetus use in determining the fate of anthropogenic
      substances.

PMID- 24111805
TI  - Review of the impact of NNRTI-based HIV treatment regimens on patient-reported
      disease burden.
AB  - While the burden of HIV disease is well documented, the value of non-nucleoside
      reverse transcriptase inhibitor (NNRTI)-based therapy regimens in reducing
      patient burden is not well understood. The purpose of this study was to examine
      patient-reported health among those receiving NNRTI-based regimens to understand
      their incremental value in reducing the burden of HIV. We conducted a structured
      literature review using PubMed to identify NNRTI trials utilizing validated
      patient-reported outcome (PRO) instruments during 2005-2011. The search strategy
      included a PubMed search to identify relevant studies based on disease,
      instrument, PRO, and NNRTI medication terms; and a manual search of
      bibliographies of identified papers. Data abstracted from each study included
      study type, treatment regimen(s), and PRO results. Of 11 trials identified, 8
      (73%) reported significance of changes in a PRO over time and 10 (91%) reported
      significance of PRO changes between groups. Several domains were assessed, with
      significant findings (between or within groups) observed in: physical health/well
      being (n = 5), emotional status/well-being (n = 2), symptoms (n = 2), anxiety (n
      = 2), gastrointestinal upset (n = 2), psychological health (n = 1), functional
      and global well-being (n = 1), fatigue/energy (n = 1), depression (n = 1), change
      in body appearance (n = 1), pain (n = 1), headache (n = 1), bad dreams/nightmares
      (n = 1), problems having sex (n = 1), and general health perception (n = 1). In
      conclusion, NNRTIs have been observed most frequently to improve patient-reported
      physical health and well-being. Treatments are needed that can also reduce
      patient burden in areas of emotional well-being, cognitive functioning, and
      overall symptom profile. 

PMID- 24111806
TI  - Antagonistic and synergistic effects of bone morphogenetic protein 2/7 and all
      trans retinoic acid on the osteogenic differentiation of rat bone marrow stromal
      cells.
AB  - The osteogenesis of bone marrow stromal cells (BMSCs) is of paramount importance
      for the repair of large-size bone defects, which may be compromised by the
      dietary-accumulated all-trans retinoic acid (ATRA). We have shown that
      heterodimeric bone morphogenetic protein 2/7 (BMP2/7) could induce bone
      regeneration in a significantly higher dose-efficiency in comparison with
      homodimeric BMPs. In this study, we evaluated the effects of ATRA and BMP2/7 on
      the proliferation, differentiation, mineralization and osteogenic genes. ATRA and
      BMP2/7 exhibited both antagonistic and synergistic effects on the osteogenesis of
      BMSCs. ATRA significantly inhibited proliferation and expression of osteocalcin
      but enhanced the activity of alkaline phosphatase of BMSCs. On day 21, 50 ng/mL
      BMP2/7 could antagonize the inhibitive effects of ATRA and significantly enhance
      osteogenesis of BMSCs. These findings suggested a promising application potential
      of heterodimeric BMP2/7 in clinic to promote bone regeneration for the cases with
      dietary accumulated ATRA. 

PMID- 24111808
TI  - Comparative in vitro effect of TiF4 to NaF and potassium oxalate on reduction of
      dentin hydraulic conductance.
AB  - Dentin hypersensitivity (DH) is related to an increase in dentin permeability.
      This study tested the effect of titanium tetrafluoride (TiF4) compared with
      sodium fluoride (NaF) and potassium oxalate gel on reducing hydraulic conductance
      (Lp) from the perspective of diminishing dentin permeability. The Lp of the
      dentin disks (1.0 +/- 0.2 mm) was evaluated using Flodec. The maximum Lp values
      of each disk were taken after phosphoric acid etching (15 seconds) and randomly
      allocated to seven groups (n=8) according to the treatments. The minimum (smear
      layer) and the maximum (after acid etching) Lp values were recorded. Treatments
      were performed for 4 minutes as follows: 1) NaF varnish 2) and solution (2.45% F,
      pH 5.0), 3) TiF4 varnish and 4) solution (2.45% F, pH 1.0), 5) 3% potassium
      oxalate gel, 6) free fluoride varnish (placebo, pH 5.0), 7) and no treatment
      (control). The Lp after each treatment was assessed. Samples were exposed to an
      erosive challenge (6% citric acid, pH 2.1, 1 minute), and the final Lp was
      recorded. The data were statistically analyzed using repeated measures two-way
      analysis of variance (p<0.05). All treatments were effective in reducing dentin
      Lp compared with the control immediately after the application. However, only
      potassium oxalate and NaF varnish significantly differed from placebo varnish
      (p<0.0001). The same results were found after the erosive challenge. Therefore,
      the TiF4 was less effective than the NaF varnish and potassium oxalate gel in
      reducing dentin permeability. Using this experimental model, both NaF varnish and
      potassium oxalate gel reduced the Lp similarly to the presence of smear layer.

PMID- 24111809
TI  - Measurement of the internal adaptation of resin composites using micro-CT and its
      correlation with polymerization shrinkage.
AB  - In the present study, the internal adaptation of dentin-composite interfaces with
      various resin composite materials under conditions of thermomechanical loading
      was analyzed nondestructively using micro-computed tomography (micro-CT), and
      these results were compared with analyses of microgaps after sectioning.
      Additionally, the correlation of internal adaptation with polymerization
      shrinkage strain and stress was evaluated. Four nonflowable resins, Gradia Direct
      (GD), Filtek P90 (P9), Filtek Z350 (Z3), and Charisma (CH), and two flowable
      resins, SDR (SD) and Tetric N-Flow (TF) were used. First, the polymerization
      shrinkage strain and stress were measured. Then, Class I cavities were prepared
      in 48 premolars. They were divided randomly into six groups, and the cavities
      were filled with composites using XP bond. To evaluate the internal adaptation,
      tooth specimens were immersed in a 25% silver nitrate solution, and micro-CT
      analysis was performed before and after thermomechanical loading. The silver
      nitrate penetration (%SP) was measured. After buccolingual sectioning and
      rhodamine penetration of the specimen, the rhodamine penetration (%RP) was
      measured using a stereo-microscope. One-way analysis of variance was then used to
      compare the polymerization shrinkage strain, stress, %SP, and %RP among the
      groups at a 95% confidence level. A paired t-test was used to compare the %SP
      before and after thermomechanical loading. Pearson correlation analysis was used
      to compare the correlation between polymerization shrinkage strain/stress and %SP
      or %RP to a 95% confidence level. Evaluation of the polymerization shrinkage
      strain demonstrated that P9 < Z3 <= GD < CH <= SD < TF (p<0.05); similarly,
      evaluation of the polymerization shrinkage stress showed that P9 <= GD <= Z3 <=
      CH <= SD < TF (p<0.05). The %SP showed that P9 <= GD <= Z3 < CH <= SD < TF
      (p<0.05) before loading and that P9 <= GD <= Z3 <= CH <= SD < TF (p<0.05) after
      loading. There was a significant difference between the before-loading and after
      loading measurements in all groups (p<0.05). Additionally, there was a positive
      correlation between the %SP and the %RP (r=0.810, p<0.001). Conclusively, the
      polymerization shrinkage stress and strain were found to be closely related to
      the internal adaptation of the resin composite restorations. The newly proposed
      model for the evaluation of internal adaptation using micro-CT and silver nitrate
      may provide a new measurement for evaluating the internal adaptation of
      restorations in a nondestructive way.

PMID- 24111810
TI  - Accuracy of ceramic restorations made using an in-office optical scanning
      technique: an in vitro study.
AB  - The present in vitro study concerns determination of the pre-cementation gap
      width of all-ceramic crowns made using an in-office digital-impression technique
      and subsequent computer-aided design/computer-aided manufacturing (CAD/CAM)
      production. Two chairside video camera systems were used: the Lava Oral scanner
      and Cadent's iTero scanner. Digital scans were made of a first molar typodont
      tooth that was suitably prepared for an all-ceramic crown. The digital
      impressions were sent via the Internet to commercial dental laboratories, where
      the crowns were made. Also, an impression of the typodont tooth was made, poured,
      and scanned in order to evaluate the pre-cementation gap of crowns produced from
      scanning stone dies. These methods and systems were evaluated by creating
      replicas of the intermediate space using an addition-cured silicone, and the gap
      widths were determined using a measuring microscope. Hot-pressed leucite
      reinforced glass-ceramic crowns were selected as a reference. The mean value for
      the marginal measuring points of the control was 170 MUm, and the values for all
      the evaluated crowns ranged from 107 to 128 MUm. Corresponding figures for the
      internal measuring points were 141-210 MUm and 115-237 MUm, respectively. Based
      on the findings in the present study, an in-office digital-impression technique
      can be used to fabricate CAD/CAM ceramic single crowns with a marginal and
      internal accuracy that is on the same level as that of a conventional hot-pressed
      glass-ceramic crown. In the present study, however, slight differences could be
      seen between the two types of ceramic crowns studied with respect to the internal
      fit obtained.

PMID- 24111811
TI  - Prediction of hemoglobin levels in whole blood donors: how to model donation
      history.
AB  - BACKGROUND: Recently, prediction models for hemoglobin (Hb) deferral risk have
      been developed. These models consider the previous Hb level plus change in Hb.
      Here, we investigated if the performance of models could be improved by
      considering more information on Hb level history. STUDY DESIGN AND METHODS: Data
      of 166,497 Dutch whole blood donors with sequential Hb measurements during 2
      years (760,444 in total) were used to develop and internally validate three
      different regression models: two simple linear models with Hb level history
      included as 1) Hb at the previous visit plus change in Hb or 2) mean of all
      previous Hb levels and one mixed-effect model including measurements of all
      previous Hb levels. RESULTS: Thirteen percent of men and 21% of women were
      deferred because of a low Hb level at least once in 2 years. The simple linear
      models and the mixed-effect model performed similar, if an estimate of the random
      intercept of the mixed-effect model was used for individual donors to calculate
      the predicted Hb level. In men, the concordance (c)-statistic ranged from 0.87 to
      0.89 and the R(2) ranged from 0.42 to 0.45. In women, the c-statistic ranged from
      0.81 to 0.84. Values of R(2) in women were higher for the simple linear models
      than for the mixed-effect model, 0.37 and 0.40 versus 0.30, respectively.
      CONCLUSION: Previous Hb levels could be summarized with one predictor as the mean
      value of all previous Hb levels. This predictor can be used in an easy-to-use
      simple linear regression model.

PMID- 24111812
TI  - Specific personality traits and general personality dysfunction as predictors of
      the presence and severity of personality disorders in a clinical sample.
AB  - This study examined the associations of specific personality traits and general
      personality dysfunction in relation to the presence and severity of Diagnostic
      and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American
      Psychiatric Association, 1994) personality disorders in a Dutch clinical sample.
      Two widely used measures of specific personality traits were selected, the
      Revised NEO Personality Inventory as a measure of normal personality traits, and
      the Dimensional Assessment of Personality Pathology-Basic Questionnaire as a
      measure of pathological traits. In addition, 2 promising measures of personality
      dysfunction were selected, the General Assessment of Personality Disorder and the
      Severity Indices of Personality Problems. Theoretically predicted associations
      were found between the measures, and all measures predicted the presence and
      severity of DSM-IV personality disorders. The combination of general personality
      dysfunction models and personality traits models provided incremental information
      about the presence and severity of personality disorders, suggesting that an
      integrative approach of multiple perspectives might serve comprehensive
      assessment of personality disorders. 

PMID- 24111814
TI  - Array tomography.
AB  - In array tomography ordered, ribbon-like assemblies of ultrathin serial sections
      are deposited on a solid substrate and imaged afterwards. The resulting images
      are then aligned and reconstructed into a three-dimensional representation of the
      object. Depending on the preparation and labelling regime, different imaging
      modalities can be applied. When using light microscopy, the labelling with
      fluorescent markers would be the obvious choice, whereas the imaging in a
      scanning electron microscope would require impregnation with heavy metals.
      Depending on preparative constraints, the combination of diverse imaging
      modalities or truly correlative imaging is possible. 

PMID- 24111813
TI  - Endogenous estradiol is not associated with poor physical health in
      postmenopausal breast cancer survivors.
AB  - BACKGROUND: Among postmenopausal breast cancer survivors, poor physical health
      has been associated with higher risks of breast cancer events. Obesity and
      physical inactivity are known risk factors for poor physical health, while
      circulating estrogen is an additional potential risk factor. We tested the
      hypothesis that the relationship between poor physical health and worse breast
      cancer outcomes is mediated by higher estrogen concentrations associated with
      body size and physical inactivity. METHODS: We used data from 1030 postmenopausal
      breast cancer survivors to examine the association between serum estradiol
      levels, body mass index (BMI), physical activity, and RAND-36-item Health Survey
      (SF-36) physical health. RESULTS: In univariate analysis, poor physical health
      was associated with higher estradiol levels, in addition to obesity and low
      physical activity. Higher estradiol levels were significantly associated with
      higher odds of poor physical health (odds ratio, OR, 1.20 [95% confidence
      interval 1.03-1.39]) in a multivariable model adjusting for age, cancer stage and
      treatment, alcohol use, and physical activity. However, the relationship between
      estradiol levels and poor physical health was no longer significant (OR 1.06
      [0.91-1.24]) after adding BMI in the model. In multivariate analysis, only poor
      physical health resulted in higher risks of recurrence (hazard ratio 1.33 [95% CI
      1.08-1.64]). CONCLUSIONS: These findings indicate that estradiol is related to
      poor physical health, but is not an independent risk factor from body size or
      inactivity. While obesity and physical activity in survivorship are potential
      targets for improving physical health, other biological processes that impact
      physical health, e.g. inflammation, remain to be identified.

PMID- 24111815
TI  - Rhinophyma-like granuloma faciale successfully treated with carbon dioxide laser.

PMID- 24111816
TI  - Efficacy and safety of sodium hypochlorite (bleach) baths in patients with
      moderate to severe atopic dermatitis in Malaysia.
AB  - Staphylococcus aureus is frequently found in patients with atopic dermatitis (AD)
      and contributes to disease exacerbation. The objective of this study was to
      evaluate the efficacy and safety of bleach baths as an adjunctive treatment in AD
      patients. Patients between 2 and 30 years old with moderate to severe AD were
      enrolled in a prospective, randomized, placebo-controlled study. Patients soaked
      in diluted bleach or distilled water baths for 10 min, twice a week for 2 months.
      Efficacy assessments included the Eczema Area and Severity Index (EASI) scores
      and S. aureus density was determined using quantitative bacterial cultures.
      Patients in the treatment group showed significant reductions in EASI scores. A
      41.9% reduction in S. aureus density from baseline was seen at 1 month further
      reducing to 53.3% at 2 months. Equal numbers of patients in both groups
      experienced mild side-effects. This study demonstrates that diluted bleach baths
      clinically improved AD in as little as 1 month. No patient withdrew from the
      treatment arm because of intolerance to the baths.

PMID- 24111817
TI  - Carbonic anhydrase IX is strongly overexpressed in adenocarcinoma in situ of the
      cervix uteri.

PMID- 24111818
TI  - Toxicological effect of engineered nanomaterials on the liver.
AB  - The liver has a crucial role in metabolic homeostasis, as it is responsible for
      the storage, synthesis, metabolism and redistribution of carbohydrates, fats and
      vitamins, and numerous essential proteins. It is also the principal
      detoxification centre of the body, removing xenobiotics and waste products by
      metabolism or biliary excretion. An increasing number of studies have shown that
      some nanomaterials (NMs) are capable of distributing from the site of exposure
      (e.g. lungs, gut) to a number of secondary organs, including the liver. As a
      secondary exposure site the liver has been shown to preferentially accumulate NMs
      (>90% of translocated NMs compared with other organs), and alongside the kidneys
      may be responsible for the clearance of NMs from the blood. Research into the
      toxicity posed by NMs to the liver is expanding due to the realization that NMs
      accumulate in this organ following exposure via a variety of routes (e.g.
      ingestion, injection and inhalation). Thus it is critical to consider what
      advances have been made in the investigation of NM hepatotoxicity, as well as
      appraising the quality of the information available and gaps in the knowledge
      that still exist. The overall aim of this review is to outline what data are
      available in the literature for the toxicity elicited by NMs to the liver in
      order to establish a weight of evidence approach (for risk assessors) to inform
      on the potential hazards posed by NMs to the liver.

PMID- 24111819
TI  - Influence of psychological attachment patterns on periodontal disease - a pilot
      study with 310 compliant patients.
AB  - OBJECTIVES: Psychosocial variables have received increased attention in
      periodontology. Attachment theory adds to known risk factors by linking early
      interactional experiences with adult tendencies of stress-regulation, health
      behaviour, symptom reporting, and healthcare utilization. The study investigates
      associations between attachment patterns and periodontal parameters. METHODS:
      Within the context of a longitudinal study on periodontal diseases, 310 patients
      with aggressive (AgP) and chronic periodontitis (CP) filled out questionnaires on
      psychological attachment patterns. The influence of attachment style on health
      behaviour, treatment attendance and utilization, and periodontal variables was
      tested. RESULTS: We found associations between psychological attachment anxiety
      on smoking and higher number of session use, independent of disease severity,
      which was more pronounced for women. Patients with higher attachment avoidance
      attended periodontal treatment later when diagnosed with CP and earlier with AgP.
      For men, we found differential associations for attachment avoidance and anxiety
      and number of teeth at beginning of treatment. CONCLUSION: Psychological
      attachment patterns are a promising target for understanding periodontal disease
      in addition to known psychosocial risk factors.

PMID- 24111820
TI  - One-step generation of engineered drug-laden poly(lactic-co-glycolic acid)
      micropatterned with Teflon chips for potential application in tendon restoration.
AB  - Regulating cellular behaviors such as cellular spatial arrangement and cellular
      phenotype is critical for managing tissue microstructure and biological function
      for engineered tissue regeneration. We herein pattern drug-laden poly(lactic-co
      glycolic acid) (PLGA) into grooves using novel Teflon stamps (that possess
      excellent properties of resistance to harsh organic solvents and molecular
      adsorption) for engineered tendon-repair therapeutics. The drug release and
      biological properties of melatonin-laden PLGA grooved micropatterns are
      investigated. The results reveal that fibroblasts cultured on the melatonin-laden
      PLGA groove micropatterns not only display significant cell alignment that mimics
      the cell behavior in native tendon, but also promote the secretion of a major
      extracellular matrix in tendon, type I collagen, indicating great potential for
      the engineering of functional tendon regeneration. 

PMID- 24111821
TI  - Forces driving the attachment of Staphylococcus epidermidis to fibrinogen-coated
      surfaces.
AB  - Cell surface proteins of bacteria play essential roles in mediating the
      attachment of pathogens to host tissues and, therefore, represent key targets for
      anti-adhesion therapy. In the opportunistic pathogen Staphylococcus epidermidis ,
      the adhesion protein SdrG mediates attachment of bacteria to the blood plasma
      protein fibrinogen (Fg) through a binding mechanism that is not yet fully
      understood. We report the direct measurement of the forces driving the adhesion
      of S. epidermidis to Fg-coated substrates using single-cell force spectroscopy.
      We found that the S. epidermidis -Fg adhesion force is of ~150 pN magnitude and
      that the adhesion strength and adhesion probability strongly increase with the
      interaction time, suggesting that the adhesion process involves time-dependent
      conformational changes. Control experiments with mutant bacteria lacking SdrG and
      substrates coated with the Fg beta(6-20) peptide, instead of the full Fg protein,
      demonstrate that these force signatures originate from the rupture of specific
      bonds between SdrG and its peptide ligand. Collectively, our results are
      consistent with a dynamic, multi-step ligand-binding mechanism called "dock,
      lock, and latch".

PMID- 24111822
TI  - The effect of abaxial retraction on pelvic geometry after pelvic symphysiotomy.
AB  - OBJECTIVE: To describe the effect abaxial retraction after pelvic symphysiotomy
      has on the geometry of the sacroiliac joints (SIs) in dogs. STUDY DESIGN:
      Experimental study. SAMPLE POPULATION: Canine cadavers (n = 9). METHODS: Canine
      cadavers free of sacroiliac disease had pelvic symphysiotomy and retraction to
      25%, 50%, 75%, and 100% of transverse sacral width, followed by axial reduction
      of the symphysis. Before symphysiotomy, after each abaxial retraction value, and
      after reduction of the symphysis each SI joint had a computed tomographic scan to
      evaluate the effect on the SI joints. RESULTS: There was no luxation at 25%
      abaxial retraction, unilateral SI luxation in three cadavers after 50% abaxial
      retraction and in all cadavers after 75% abaxial retraction. Axial reduction of
      the symphysis resolved all luxations. CONCLUSIONS: Pelvic symphysiotomy and
      abaxial retraction between 50% and 75% of transverse sacral width leads to
      unilateral SI luxation, which is resolved by axial reduction. While not likely
      requiring ancillary stabilization, SI joint luxation may be a cause for
      additional postoperative pain, reluctance to ambulate, and prolonged
      hospitalization/recovery.

PMID- 24111823
TI  - Clinical trial simulation to assist in COPD trial planning and design with a
      biomarker-based diagnostic: when to pull the trigger?
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a
      wide range of clinical phenotypes that vary from predominantly airway disease
      (chronic bronchitis) to predominantly parenchymal disease (emphysema). Current
      advances for the treatment of COPD are increasingly focused on targeted
      treatments and development of novel biomarker-based diagnostics (Dx)'s to select
      the patients most likely to benefit. Clinical trial planning and design with
      biomarkers includes additional considerations beyond those for conventional
      trials in un-selected populations, e.g., the heterogeneity of COPD phenotypes in
      the population, the ability of a biomarker to predict clinically meaningful
      phenotypes that are differentially associated with the response to a targeted
      treatment, and the data needed to make Go/No Go decisions during clinical
      development. We developed the Clinical Trial Object Oriented Research Application
      (CTOORA), a computer-aided clinical trial simulator of COPD patient outcomes, to
      inform COPD trial planning with biomarkers. CTOORA provides serial projections of
      trial success for a range of hypothetical and plausible scenarios of interest. In
      the absence of data, CTOORA can identify characteristics of a biomarker-based Dx
      needed to provide a meaningful advantage when used in a clinical trial. We
      present a case study in which CTOORA is used to identify the scenarios for which
      a biomarker may be used successfully in clinical development. CTOORA is a tool
      for robust clinical trial planning with biomarkers, to guide early-to-late stage
      development that is positioned for success.

PMID- 24111824
TI  - Comparison of attitudes towards dental education among dental students in Japan
      and China.
AB  - The aim of this study was to identify and compare the attitudes of dental
      students towards dental education in Japan and China. Fifty-four dental students
      from the Stomatology School of China Medical University and 51 dental students
      from the Dental Faculty of Kyushu University, Japan, participated in this study.
      Information was derived from a self-answered questionnaire consisting of 11
      items. Significant differences in the responses of the participants from the two
      countries were detected for 10 of the questionnaire items (P < 0.05). Nearly
      three-quarters of the Japanese students were satisfied with the teaching
      faculties of their schools, while only a quarter of the Chinese students
      indicated satisfaction. A total of 69% of Chinese students thought that learning
      a foreign language wasted too much time compared with none of the Japanese
      students. A student-oriented teaching mode was not well accepted by either of the
      groups, and 62% of Chinese students and 53% of Japanese students wanted to
      increase the duration of the clinical practice stage of education. The findings
      from this study enhance our understanding of differences and/or similarities
      among dental students in the two nations. This information may help to define
      strategies to improve the quality of dental education, and especially exchange
      programmes of international students. 

PMID- 24111825
TI  - Regulation of protein tyrosine phosphatase oxidation in cell adhesion and
      migration.
AB  - SIGNIFICANCE: Redox-regulated control of protein tyrosine phosphatases (PTPs)
      through inhibitory reversible oxidation of their active site is emerging as a
      novel and general mechanism for control of cell surface receptor-activated
      signaling. This mechanism allows for a previously unrecognized crosstalk between
      redox regulators and signaling pathways, governed by, for example, receptor
      tyrosine kinases and integrins, which control cell proliferation and migration.
      RECENT ADVANCES: A large number of different molecules, in addition to hydrogen
      peroxide, have been found to induce PTP inactivation, including lipid peroxides,
      reactive nitrogen species, and hydrogen sulfide. Characterization of oxidized
      PTPs has identified different types of oxidative modifications that are likely to
      display differential sensitivity to various reducing systems. Accumulating
      evidence demonstrates that PTP oxidation occurs in a temporally and spatially
      restricted manner. Studies in cell and animal models indicate altered PTP
      oxidation in models of common diseases, such as cancer and
      metabolic/cardiovascular disease. Novel methods have appeared that allow
      characterization of global PTP oxidation. CRITICAL ISSUES: As the understanding
      of the molecular and cellular biology of PTP oxidation is developing, it will be
      important to establish experimental procedures that allow analyses of PTP
      oxidation, and its regulation, in physiological and pathophysiological settings.
      Future studies should also aim to establish specific connections between various
      oxidants, specific PTPs, and defined signaling contexts. FUTURE DIRECTIONS:
      Modulation of PTP activity still appears as a valid strategy for correction or
      inhibition of dys-regulated cell signaling. Continued studies on PTP oxidation
      might present yet unrecognized means to exploit this regulatory mechanism for
      pharmacological purposes.

PMID- 24111826
TI  - Sensitivity of nanostructure in charged cubosomes to phase changes triggered by
      ionic species in solution.
AB  - The phase behavior of dispersions comprising mixed ionic surfactant and
      phytantriol was precisely controlled by varying the ionic surfactant content in
      the mixed lipid and the ionic strength in the system. Two important trends in the
      phase transition of the mixed lipid systems were identified: (1) An increase in
      the ionic surfactant content increased the curvature of the self-assembled system
      toward the hydrophobic region, resulting in the phase transition from cubic phase
      to lamellar phase. (2) An increase in ionic strength decreased repulsion between
      the headgroups of the ionic surfactant, resulting in a phase transition from
      lamellar phase to cubic phase. The phase transitions were confirmed using small
      angle X-ray scattering and cryo-TEM and were strongly correlated with the visual
      turbidity of the dispersions. The lipid mixture with anionic surfactant showed
      high sensitivity to multivalent cations for triggering the phase transition,
      which may be a potential strategy to develop a detection/treatment system for
      toxic multivalent metallic cations such as chromium. 

PMID- 24111827
TI  - Thermokinetic origin of luminescent traveling fronts in the H2O2-NaOH-SCN(-)-Cu2+
      homogeneous oscillator: experiments and model.
AB  - According to our original discovery, the oscillatory course of the Cu(2+)
      catalyzed oxidation of thiocyanate ions with hydrogen peroxide, in nonstirred
      medium and upon the addition of luminol as an indicator, can be a source of a
      novel type of dissipative patterns--luminescent traveling waves. The formation of
      these fronts, contrary to the patterns associated with the Belousov-Zhabotinsky
      reaction, cannot be explained in terms of coupled homogeneous kinetics and
      diffusion, and under isothermal conditions. Both experimental studies and
      numerical simulations of the kinetic mechanism suggest that the spatial progress
      of these waves requires mainly the temperature gradient in the solution, which
      affects the local chemical reaction rate (and thus the oscillation period), with
      practically negligible contribution from diffusion of reagents. As a consequence
      of this thermokinetic coupling, the observed traveling patterns are thus
      essentially the phase (or kinematic) waves, formed due to the spatial phase shift
      of the oscillations caused by differences in chemical reaction rates. The
      temperature gradient, caused by the significant heat effect of exothermic
      oxidation of thiocyanate by hydrogen peroxide, can emerge spontaneously as a
      local fluctuation or can be forced externally, if the control of progress of the
      luminescent waves is to be achieved.

PMID- 24111828
TI  - Potentials of proniosomes for improving the oral bioavailability of poorly water
      soluble drugs.
AB  - Abstract Objective: The objectives of this study were, first, to develop a free
      flowing and stable proniosome formulation for poorly water-soluble drugs such as
      vinpocetine; and second, to estimate its bioavailability as oral drug delivery
      system. METHODS: The proniosomes consisting of span60, cholesterol, sorbitol and
      vinpocetine were prepared by a novel approach. After the proniosomes were
      contacted with water, the suspension of vinpocetine-loaded niosomes formed
      automatically. The proniosomes and reconstituted niosomes were evaluated for
      their physicochemical characteristics, in vitro drug dissolution and release,
      integrity and stability at different GI tract pH conditions, in situ single-pass
      intestinal perfusion and in vivo bioavailability. RESULTS: The proniosome powder
      exhibited excellent flowability. The reconstituted niosomes with high drug
      entrapment efficiency (89.67 +/- 3.28%) showed spherical morphology with smooth
      surface under transmission electron microscope (TEM). X-ray diffraction (XRD)
      indicated that the drug was in an amorphous or molecular state in proniosome
      powder. In vitro dissolution and release study, proniosomes did enhance the
      dissolution and release rate compared to vinpocetine suspension in phosphate
      buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity
      and stability at different GI tract pH conditions. The in situ single-pass
      intestinal perfusion indicated that encapsulation of vinpocetine into niosomes
      could largely improved the absorption of vinpocetine. The AUC(0-infinity) of F2
      and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine
      suspension, respectively. The results demonstrated the proniosomes indeed
      remarkably enhanced the oral bioavailability of vinpocetine. CONCLUSION: This
      study suggested the potential of proniosomes as stable precursors for the
      immediate preparation of niosome carrier systems.

PMID- 24111829
TI  - Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf
      extract of Parthenium hystrophorus L in aqueous media and Gentamicin sulphate: in
      vitro.
AB  - Monodisperse silver (Ag) nanoparticles were synthesized by using Parthenium
      hystrophorus L leaf extract in aqueous media. The synthesized nanoparticles were
      characterized by using UV-vis spectrophotometer, X-ray diffracto-meter (XRD),
      transmission electron microscope (TEM), and dynamics light scattering (DLS). Size
      dependent antibacterial activities of Ag nanoparticles were tested against Gram
      negative Pseudomonas aeruginosa and Gram positive Staphylococcus aureus. Ag
      nanoparticles having 20 +/- 2 nm size in diameter show maximum zone of inhibition
      (23 +/- 2.2 mm) in comparison to 40 nm and 70 nm diameter nanoparticles for
      Pseudomonas aeruginosa. The zone of inhibition against Staphylococcus aureus were
      19 +/- 1.8 mm, 15 +/- 1.5 mm and 11 +/- 1 mm for 20 nm, 40 nm, and 70 nm,
      respectively. In addition, affect of concentration of 20 nm size Ag nanoparticles
      on Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus
      aureus species were also reported and results were compared with 10 ug/ml dose of
      Gentamicin sulphate. The Parthenium hystrophorus L leaf extract capped 20 +/- 2
      nm Ag nanoparticles (7.5 ug/ml) shows statistically significant antibacterial
      activity than Gentamicin sulphate (10 ug/ml) against Staphylococcus aureus.

PMID- 24111830
TI  - Influence of filler selection on twin screw foam granulation.
AB  - The influence of filler selection in wet granulation was studied for the novel
      case where the binder is delivered as an unstable, semi-rigid aqueous foam to an
      extrusion process. The work primarily examined the impact of differing
      concentrations of microcrystalline cellulose (Avicel PH(r) 101) in a formulation
      with spray-dried alpha-lactose monohydrate (Flowlac(r) 100) in regards to wetting
      and granule nucleation for this relatively new technique known as continuous foam
      granulation. Foam stability was varied within the work to change its drainage and
      coarsening behavior atop these powder excipients, by use of different foamable
      binding agents (METHOCELTM F4 PLV and METHOCELTM Premium VLV) as well as by
      adjusting the foam quality. A static bed penetration test was first used to study
      the foam behavior in wetting these powders without the processing constraints of
      an extruder which limit possible liquid-to-solids ratios as well as introduce
      shear which may complicate interpretation of the mechanism. The test found that
      the penetration time to saturate these powders decreased as their water
      absorption capacity increased which in turn decreased the size of the formed
      nuclei. Differences in the stability of the foamed binder had minimal influence
      on these attributes of wetting despite its high spread-to-soak behavior. The size
      of granules produced by extrusion similarly demonstrated sensitivity to the
      increasing water absorption capacity of the filler and little dependency on foam
      properties. The different liquid-to-solids ratios required to granulate these
      different formulations inside the extruder highlighted an evolving concept of
      powder lubricity for continuous foam granulation.

PMID- 24111831
TI  - Non-destructive prediction of the drug content of an acetaminophen suppository by
      near-infrared spectroscopy and X-ray computed tomography.
AB  - The purpose of this study is to develop non-destructive methods to determine the
      drug content of suppositories using near-infrared (NIR) spectrometry and X-ray
      computed tomography (XCT). The suppository samples (acetaminophen content: 0,
      100, 200, 300, 400 and 500 mg/suppository) consisted of acetaminophen powder and
      hard fat. NIR spectra of 18 standard suppository samples were recorded, and the
      data were divided into two wave number ranges, 4000-10 000 cm(-1) (LR), and 4280
      6650 cm(-1) (SR). The best calibration model was determined to minimize the
      standard error of cross-validation (SECV) by the leave-one-out method in the
      partial least squares regression (PLS). Sliced XCT images of the suppositories
      were measured, and apparent density (AD) was evaluated using the image of the
      sample. The NIR models gave the best correlation coefficient constant (R) values,
      since the results for LR and SR gave straight lines with R of 0.9274 and 0.9707,
      respectively. The AD of the suppositories by XCT increased with increasing drug
      content, and the relationship between the AD and drug content had a straight line
      with R of 0.9958. Both NIR and X-ray CT performed accurate measurements of
      suppository samples through plastic packaging.

PMID- 24111832
TI  - Manufacture and characteristics of asymmetric membrane capsule shells with a
      novel wet phase inversion method.
AB  - In order to overcome the difficulty in stripping and to improve the automaticity
      and efficiency, a novel method was developed to prepare asymmetric membrane
      capsule shells (AM-CSs). Soluble mold pins were used to replace conventional
      insoluble mold pins, and simplified process was designed. Investigated by
      scanning electron microscopy and dye test, the homemade AM-CSs had typical
      asymmetric structure, in situ pore formation ability and high water influx. The
      in vitro dissolution properties of AM-CSs and homogeneous membrane capsule shells
      (HM-CSs) were compared. The release behavior of Metoprolol Tartrate and
      Nimodipine from the AM-CSs was mainly dominated by osmosis, while no drug could
      release from HM-CSs. The novel wet phase inversion method had significant
      advantages as well as potential value to be used in pharmaceutical research and
      application.

PMID- 24111833
TI  - Rational design of porous coordination polymers based on bis(phosphine)MCl2
      complexes that exhibit high-temperature H2 sorption and chemical reactivity.
AB  - MCl2 complexes of a new p-carboxylated 1,2-bis(diphenylphosphino)benzene ligand
      are effectively utilized as tetratopic building blocks to prepare isostructural
      porous coordination polymers with accessible reactive metal sites (M = Pd, Pt).
      The crystalline materials exhibit unusual and fully reversible H2 sorption at 150
      degrees C. Post-synthetic reactivity is also possible, in which Pt-Cl bonds can
      be activated to provide organometallic species in the pores. 

PMID- 24111834
TI  - Reduced incidence of lower-extremity amputations in a Danish diabetes population
      from 2000 to 2011.
AB  - AIMS: Diabetic foot disease and amputations severely reduce quality of life and
      have major economic consequences. The aim of this study was to estimate time
      trends in the incidence of lower-extremity amputations in Danish people with
      diabetes. METHODS: We studied major and minor lower-extremity amputations from
      2000 to 2011 among 11,332 people with diabetes from the Steno Diabetes Center.
      Amputations were identified by linkage of the electronic medical system with the
      National Patient Registry. Sex-specific incidence rates of amputations by age,
      diabetes duration, calendar time and diabetes type were modelled by Poisson
      regression. RESULTS: From 2000 to 2011, 384 incident lower-extremity amputations
      (205 major, 179 minor) occurred during 100,495 years of patient follow-up. From
      2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5%
      among men and 47.4% among women with type 1 diabetes and by 83.3% among men and
      79.1% among women with type 2 diabetes (P < 0.001). In particular, there was a
      decline in major lower-extremity amputations. In 2011, the incidence rates of
      major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21
      (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56
      (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000
      patient-years at age 70 years. No significant change in incidence of minor
      amputations was observed. CONCLUSION: The incidence of major lower-extremity
      amputations reduced significantly from 2000 to 2011 in Danish people with
      diabetes followed at a diabetes specialist centre.

PMID- 24111835
TI  - Motives for meaningful involvement in rural AIDS service organizations.
AB  - The research described herein was a three-year exploratory descriptive study to
      examine how meaningful involvement (MIPA) is conceptualized and experienced in
      rural regions of the Maritime provinces of Canada. The focus of this paper is one
      aspect of the research; i.e., what motivates the clients of AIDS Service
      Organizations (ASOs) in rural Canada to become meaningfully involved? We
      interviewed 34 people who were past or current clients of ASOs in Maritime Canada
      and who self-reported as engaging in at-risk behaviors for HIV or living with
      HIV. The interviews explored participants' perspectives about their motives for
      becoming meaningfully involved in an ASO. Three themes regarding motives for MIPA
      were revealed: (1) meeting personal needs; (2) making a difference to others; and
      (3) recognizing a fit between their skills, goals, needs and the opportunities
      and experiences within the ASO and with other ASO clients. Participants generally
      cited more than one motive. This research study contributed to the field of
      knowledge about the motives for MIPA in which it reveals (1) that MIPA was
      conceptualized by the rural ASO clients as whatever participation provided them
      personal meaning (i.e., by fulfilling a personal need, by making a difference,
      and by recognizing a fit) and (2) the important role that ASO staff and
      volunteers have in fostering and sustaining MIPA. The study also highlighted a
      trajectory of involvements that support the need for ASOs to entertain a wide
      range of roles that are assumed as MIPA. 

PMID- 24111836
TI  - Flooding enzymes: quantifying the contributions of interstitial water and cavity
      shape to ligand binding using extended linear response free energy calculations.
AB  - Glutamate racemase (GR) is a cofactor independent amino acid racemase that has
      recently garnered increasing attention as an antimicrobial drug target. There are
      numerous high resolution crystal structures of GR, yet these are invariably bound
      to either D-glutamate or very weakly bound oxygen-based salts. Recent in silico
      screens have identified a number of new competitive inhibitor scaffolds, which
      are not based on D-Glu, but exploit many of the same hydrogen bond donor
      positions. In silico studies on 1-H-benzimidazole-2-sulfonic acid (BISA) show
      that the sulfonic acid points to the back of the GR active site, in the most
      buried region, analogous to the C2-carboxylate binding position in the GR-d
      glutamate complex. Furthermore, BISA has been shown to be the strongest nonamino
      acid competitive inhibitor. Previously published computational studies have
      suggested that a portion of this binding strength is derived from complexation
      with a more closed active site, relative to weaker ligands, and in which the
      internal water network is more isolated from the bulk solvent. In order to
      validate key contacts between the buried sulfonate moiety of BISA and moieties in
      the back of the enzyme active site, as well as to probe the energetic importance
      of the potentially large number of interstitial waters contacted by the BISA
      scaffold, we have designed several mutants of Asn75. GR-N75A removes a key
      hydrogen bond donor to the sulfonate of BISA, but also serves to introduce an
      additional interstitial water, due to the newly created space of the mutation. GR
      N75L should also show the loss of a hydrogen bond donor to the sulfonate of
      BISA, but does not (a priori) seem to permit an additional interstitial water
      contact. In order to investigate the dynamics, structure, and energies of this
      water-mediated complexation, we have employed the extended linear response (ELR)
      approach for the calculation of binding free energies to GR, using the YASARA2
      knowledge based force field on a set of ten GR complexes, and yielding an R
      squared value of 0.85 and a RMSE of 2.0 kJ/mol. Surprisingly, the inhibitor set
      produces a uniformly large interstitial water contribution to the electrostatic
      interaction energy (<V(el)>), ranging from 30 to >50%, except for the natural
      substrate (D-glutamate), which has only a 7% contribution of <V(el)> from water.
      The broader implications for predicting and exploiting significant interstitial
      water contacts in ligand-enzyme complexation are discussed.

PMID- 24111837
TI  - Beyond rodent models of pain: non-human primate models for evaluating novel
      analgesic therapeutics and elaborating pain mechanisms.
AB  - Evaluation of potential analgesic therapeutics and the elaboration of the
      neurobiology of pain have heavily relied on pain models developed in rodents.
      However, a limitation of rodents is their phylogenetic distance from humans,
      which could in part account for the failure of some preclinical findings to
      translate to clinical utility. By contrast, given their genetic closeness and
      phenotypic similarities to humans, it is suggested that there be greater
      utilization of non-human primates (NHP) in preclinical pain studies. Methods to
      induce chronic pain-like states and quantify changes in nociception that have
      been developed in rodents could be adapted to the NHP. Similarly, human
      experimental injury-induced sensitization, which attempts to temporarily mimic
      the neuropathology and symptoms observed in the chronic pain state, could be
      adapted to the NHP. The NHP could then serve as a platform to validate human
      experimental models as well as proof-of-concept studies. Beyond experimentally
      modeled pain states, a number of naturally occurring disease states, such as
      osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis
      testing and proof-of-concept studies. While NHP studies are logistically
      cumbersome, it is envisioned that NHP pain models will add value to current
      preclinical data and greatly facilitate the discovery of novel analgesic
      treatments. 

PMID- 24111838
TI  - Effects of resveratrol supplementation on plasma lipids: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - A systematic review and meta-analysis of available evidence was conducted to
      obtain a conclusive result on the lipid-modulating effects of resveratrol. Seven
      randomized controlled trials with a total of 282 subjects (141 in each group) met
      the eligibility criteria. Overall, resveratrol supplementation had no significant
      effect on any of the lipid parameters assessed: total cholesterol (weighted mean
      difference [WMD] -8.70; 95% confidence interval [95% CI] -21.54-4.14; P = 0.18),
      low-density lipoprotein cholesterol (WMD -3.22; 95% CI -12.56-6.12); P = 0.50),
      high-density lipoprotein cholesterol (WMD -0.26; 95% CI -4.25-3.73; P = 0.90),
      and triglycerides (WMD -4.30; 95% CI -20.22-11.63; P = 0.60). These results were
      robust in sensitivity analysis and were not dependent on the resveratrol dose,
      the duration of supplementation, or the cardiovascular risk status of the
      population studied. While future large-scale, well-designed trials are warranted,
      the current evidence suggests that mechanisms other than hypolipidemic effects
      account for the established cardioprotective properties of resveratrol. 

PMID- 24111839
TI  - Clinical profile of isolated viral anterior uveitis in a South Indian patient
      population.
AB  - AIM: To analyze the clinic profile of polymerase chain reaction proven viral
      anterior uveitis in a south Indian patient population. MATERIALS & METHODS:
      Retrospective, nonrandomized study between January 2009 and July 2012. RESULTS:
      Out of the 36 patients with polymerase chain reaction (PCR)-positive viral
      anterior uveitis, 24 patients had varicella zoster virus (VZV) anterior uveitis,
      7 patients had HSV anterior uveitis, 3 patients had cytomegalovirus (CMV)
      anterior uveitis, and 2 patients had chikungunya virus related anterior uveitis.
      Corneal involvement was seen in 21 cases (58.33%). An altered iris pattern was
      seen in 14 cases (38.89%). Increase in intraocular pressure (IOP) at the time of
      inflammation was seen in 10 cases (27.78%). Reactivations were seen in 22 cases
      (61.11%). A comparison of herpes simplex virus (HSV)- and VZV-related anterior
      uveitis did not reveal any significant factors except for a previous history of
      herpes zoster in VZV-associated uveitis. CONCLUSION: We see isolated viral
      anterior uveitis related to HSV, VZV, CMV, and chikungunya viruses in our patient
      population. Corneal involvement, pigmented keratic precipitates, an abnormal iris
      pattern, increase in IOP, and reactivations are seen as a spectrum of viral
      anterior uveitis in our patient population as well.

PMID- 24111840
TI  - Risk assessment of multistate progression of breast tumor with state-dependent
      genetic and environmental covariates.
AB  - Few studies have focused on the different roles risk factors play in the
      multistate temporal natural course of breast cancer. We proposed a three-state
      Markov regression model to predict the risk from free of breast cancer (FBC) to
      the preclinical screen-detectable phase (PCDP) and from the PCDP to the clinical
      phase (CP). We searched the initiators and promoters affecting onset and
      subsequent progression of breast tumor to build up a three-state temporal natural
      history model with state-dependent genetic and environmental covariates. This
      risk assessment model was applied to a 1 million Taiwanese women cohort. The
      proposed model was verified by external validation with another independent data
      set. We identified three kinds of initiators, including the BRCA gene, seven
      single nucleotides polymorphism, and breast density. ER, Ki-67, and HER-2 were
      found as promoters. Body mass index and age at first pregnancy both played a
      role. Among women carrying the BRCA gene, the 10-year predicted risk for the
      transition from FBC to CP was 25.83%, 20.31%, and 13.84% for the high-,
      intermediate-, and low-risk group, respectively. The corresponding figures were
      1.55%, 1.22%, and 0.76% among noncarriers. The mean sojourn time of staying at
      the PCDP ranged from 0.82 years for the highest risk group to 6.21 years for the
      lowest group. The lack of statistical significance for external validation
      (x(4)2=5.30,p=0.26) revealed the adequacy of our proposed model. The three-state
      model with state-dependent covariates of initiators and promoters was proposed
      for achieving individually tailored screening and also for personalized clinical
      surveillance of early breast cancer. 

PMID- 24111842
TI  - Identification of novel mutation in the HR gene responsible for atrichia with
      papular lesions in a Pakistani family.

PMID- 24111843
TI  - Stem cells, tissue engineering and periodontal regeneration.
AB  - The aim of this review is to discuss the clinical utility of stem cells in
      periodontal regeneration by reviewing relevant literature that assesses the
      periodontal-regenerative potential of stem cells. We consider and describe the
      main stem cell populations that have been utilized with regard to periodontal
      regeneration, including bone marrow-derived mesenchymal stem cells and the main
      dental-derived mesenchymal stem cell populations: periodontal ligament stem
      cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth,
      stem cells from apical papilla and dental follicle precursor cells. Research into
      the use of stem cells for tissue regeneration has the potential to significantly
      influence periodontal treatment strategies in the future.

PMID- 24111844
TI  - Hemilaminectomy for thoracolumbar Hansen Type I intervertebral disk disease in
      ambulatory dogs with or without neurologic deficits: 39 cases (2008-2010).
AB  - OBJECTIVE: To describe prognostic factors, outcome, and time to recovery among
      ambulatory dogs having hemilaminectomy for Hansen Type I intervertebral disk
      disease. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 38; 39
      hemilaminectomies). METHODS: Medical records (January 2008-May 2010) on all dogs
      that had hemilaminectomy for Hansen Type I intervertebral disk disease were
      reviewed. Records for dogs that were ambulatory preoperatively were analyzed for
      signalment, duration and severity of signs, presence of neurologic deficits, and
      postoperative outcome. Dogs were categorized based on Frankel score and
      subcategorized by their level of conscious proprioceptive (CP) deficit.
      Postoperatively, time to ambulation and to regain normal CP responses was
      recorded. Results for each group were compared using a chi(2) test and considered
      significant when P < .05. Recovery times were analyzed using a Cox proportional
      hazards model. RESULTS: Seven dogs were categorized as modified Frankel grade I
      preoperatively and 32 dogs as grade II with varying levels of deficits (1 of
      these dogs had previously been operated as grade II and was reoperated again as
      grade II). Increasing degree of CP deficit preoperatively was significantly
      correlated with longer time to ambulation (P = .005) as well as longer time to CP
      normal (P = .01). Duration of signs was not significantly correlated with time to
      ambulation or neurologic recovery for either grade I or II dogs. CONCLUSIONS:
      Most dogs recovered well with surgical decompression. Increasing degree of
      deficits preoperatively is significantly correlated with longer recovery time.

PMID- 24111845
TI  - Validation of the i-BODE index as a predictor of hospitalization and mortality in
      patients with COPD participating in pulmonary rehabilitation.
AB  - Abstract The aim of this study was to examine the value of the i-BODE index to
      predict hospital admission and to confirm its usefulness to predict mortality in
      a Danish population. The incremental shuttle walking test (ISWT) is widely used
      in the UK and Europe and previous work has examined the replacement of the 6MWT
      with the ISWT within the BODE index for predicting the prognosis of COPD (i
      BODE). The 674 patients included in the analysis participated in a 7-week
      pulmonary rehabilitation program from 2002 to 2011. The National Health Services
      Central Register ascertained vital status and provided information on all
      hospital admissions. The mean follow-up period was 66 months (range 11-118
      months). Cox proportional hazards model was used to identify factors that
      significantly predicted mortality and time to first hospital admission. The i
      BODE index as well as body mass index, MRC dyspnea grade, and exercise capacity
      (ISWT) were significantly associated with all-cause mortality. The adjusted
      hazard ratio for death per one point increase in the i-BODE score was 1.28 (95%
      confidence interval 1.20 to 1.37). The i-BODE index was also a significant
      predictor of hospitalization, both for all causes and COPD exacerbation. Patients
      in the highest i-BODE quartile had a median time to first hospitalization of 17
      months compared to 51 months for patients in the lowest quartile. The i-BODE
      index is a significant predictor of hospital admission and thus health care
      utilization, and also mortality. 

PMID- 24111847
TI  - Type 2A Koebner phenomenon in vitiligo is distinct from other subtypes:
      observations from an Indian cohort.
AB  - BACKGROUND: Koebner phenomenon (KP) in vitiligo has been redefined and classified
      recently. OBJECTIVES: To study the clinical characteristics of various grades of
      KP. METHODS: In this prospective cross-sectional study, 202 patients with
      vitiligo were studied between January 2011 and December 2012 for the presence of
      KP. Based on the new Vitiligo European Task Force guidelines, KP was classified
      as type 1-3 and grades Iota-IV. Disease characteristics were studied in the
      various groups and subgroups based on the presence of KP. RESULTS: Koebner
      phenomenon was seen in 130 of 202 patients. The mean age of patients showing KP
      was 23.9 +/- 13.6 years, compared with 19.3 +/- 12.4 years for patients not
      showing KP (P = 0.02). The mean body surface area involved in the KP-positive
      group was 4.6 +/- 5.6%, vs. 1.5 +/- 1.1% in the KP-negative group (P = 0.001).
      Fifty-five patients experiencing KP received low-dose dexamethasone oral
      minipulse therapy compared with nine of those who did not (P = 0.01). Of the 130
      patients with KP, grade Iota KP was seen in 32, grade II KP in 116, grade III KP
      in 22 and grade IV KP in 16. There was a significant difference between type 1
      and type 2A KP, and between type 2A and type 2B KP. In contrast, type 1 and type
      2B KP were found not to be significantly different and had a good degree of
      correlation. CONCLUSIONS: Patients with KP have a significantly higher age at
      onset, more extensive cutaneous involvement and are more likely to receive
      systemic steroids for disease control. Type 2A disease was found to be distinct
      from the other subtypes.

PMID- 24111846
TI  - Skin, reactive oxygen species, and circadian clocks.
AB  - SIGNIFICANCE: Skin, a complex organ and the body's first line of defense against
      environmental insults, plays a critical role in maintaining homeostasis in an
      organism. This balance is maintained through a complex network of cellular
      machinery and signaling events, including those regulating oxidative stress and
      circadian rhythms. These regulatory mechanisms have developed integral systems to
      protect skin cells and to signal to the rest of the body in the event of internal
      and environmental stresses. RECENT ADVANCES: Interestingly, several signaling
      pathways and many bioactive molecules have been found to be involved and even
      important in the regulation of oxidative stress and circadian rhythms, especially
      in the skin. It is becoming increasingly evident that these two regulatory
      systems may, in fact, be interconnected in the regulation of homeostasis.
      Important examples of molecules that connect the two systems include serotonin,
      melatonin, vitamin D, and vitamin A. CRITICAL ISSUES: Excessive reactive oxygen
      species and/or dysregulation of antioxidant system and circadian rhythms can
      cause critical errors in maintaining proper barrier function and skin health, as
      well as overall homeostasis. Unfortunately, the modern lifestyle seems to
      contribute to increasing alterations in redox balance and circadian rhythms,
      thereby posing a critical problem for normal functioning of the living system.
      FUTURE DIRECTIONS: Since the oxidative stress and circadian rhythm systems seem
      to have areas of overlap, future research needs to be focused on defining the
      interactions between these two important systems. This may be especially
      important in the skin where both systems play critical roles in protecting the
      whole body.

PMID- 24111849
TI  - Four levels of wavelength-selective uncaging for oligonucleotides.
AB  - In this study the new nucleobase-caged nucleotides dT(NpHP) and dT(DEACM) are
      introduced. Together with two other caging groups (NDBF and NPP) this results in
      four layers of wavelength-selective uncaging for oligonucleotides, sequentially
      going from 505 to 440 nm, 365 nm, and finally to 313 nm for the photolysis
      reaction. 

PMID- 24111848
TI  - Plasminogen-stimulated airway smooth muscle cell proliferation is mediated by
      urokinase and annexin A2, involving plasmin-activated cell signalling.
AB  - BACKGROUND AND PURPOSE: The conversion of plasminogen into plasmin by
      interstitial urokinase plasminogen activator (uPA) is potentially important in
      asthma pathophysiology. In this study, the effect of uPA-mediated plasminogen
      activation on airway smooth muscle (ASM) cell proliferation was investigated.
      EXPERIMENTAL APPROACH: Human ASM cells were incubated with plasminogen (0.5-50
      MUg.mL(-1) ) or plasmin (0.5-50 mU.mL(-1) ) in the presence of pharmacological
      inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by
      increases in cell number or MTT reduction after 48 h incubation with
      plasmin(ogen), and by earlier increases in [(3) H]-thymidine incorporation and
      cyclin D1 expression. KEY RESULTS: Plasminogen (5 MUg.mL(-1) )-stimulated
      increases in cell proliferation were attenuated by UK122 (10 MUM) or by
      transfection with uPA gene-specific siRNA. Exogenous plasmin (5 mU.mL(-1) ) also
      stimulated increases in cell proliferation. Inhibition of plasmin-stimulated
      ERK1/2 or PI3K/Akt signalling attenuated plasmin-stimulated increases in ASM
      proliferation. Furthermore, pharmacological inhibition of cell signalling
      mediated by the EGF receptor, a receptor trans-activated by plasmin, also reduced
      plasmin(ogen)-stimulated cell proliferation. Knock down of annexin A2, which has
      dual roles in both plasminogen activation and plasmin-signal transduction, also
      attenuated ASM cell proliferation following incubation with either plasminogen or
      plasmin. CONCLUSIONS AND IMPLICATIONS: Plasminogen stimulates ASM cell
      proliferation in a manner mediated by uPA and involving multiple signalling
      pathways downstream of plasmin. Targeting mediators of plasminogen-evoked ASM
      responses, such as uPA or annexin A2, may be useful in the treatment of asthma.

PMID- 24111850
TI  - Response to Heinzerling (Insulin allergy) and to Jacquier et al. (A practical,
      clinical approach to the assessment and management of suspected insulin allergy).

PMID- 24111852
TI  - Curing of a bisphenol E based cyanate ester using magnetic nanoparticles as an
      internal heat source through induction heating.
AB  - We report on the control of cyclotrimerization forming a polycyanurate polymer
      using magnetic iron oxide nanoparticles in an alternating-current (ac) field as
      an internal heat source, starting from a commercially available monomer. Magnetic
      nanoparticles were dispersed in the monomer and catalytic system using
      sonication, and the mixture was subjected to an alternating magnetic field,
      causing the magnetic nanoparticles to dissipate the energy of the magnetic field
      in the form of heat. Internal heating of the particle/monomer/catalyst system was
      sufficient to start and sustain the polymerization reaction, producing a cyanate
      ester network with conversion that compared favorably to polymerization through
      heating in a conventional laboratory oven. The two heating methods gave similar
      differential scanning calorimetry temperature profiles, conversion rates, and
      glass transition temperatures when using the same temperature profile. The
      ability of magnetic nanoparticles in an ac field to drive the curing reaction
      should allow for other reactions forming high-temperature thermosetting polymers
      and for innovative ways to process such polymers. 

PMID- 24111851
TI  - Adsorption of alkyltrimethylammonium bromides at water/alkane interfaces:
      competitive adsorption of alkanes and surfactants.
AB  - The adsorption of members of the homologous series of alkyl trimethylammonium
      bromides (C(n)TAB) is studied at water/alkane interfaces by drop profile analysis
      tensiometry. The results are discussed in terms of a competitive adsorption
      process of alkane and surfactant molecules. A thermodynamic model, derived
      originally for the adsorption of surfactant mixtures, is adapted such that it
      describes a competitive adsorption of the surfactant molecules from the aqueous
      phase and alkane molecules from the oil phase. This new model involves the
      interspecies attraction coefficient, which mutually increases the adsorption
      activities of the alkane and C(n)TAB. The effects of the alkyl chain length n of
      C(n)TABs and the influence of the number of C atoms in the alkane chain are
      discussed, and the physical quantities are compared to those determined at the
      aqueous solution/air interface. The new theoretical model for aqueous
      solution/oil interfaces is also compared to a theory that does not consider the
      adsorption of alkane. The proposed new model demonstrates good agreement with the
      experimental data.

PMID- 24111853
TI  - Effects of family caregivers on the use of formal long-term care in South Korea.
AB  - AIM: We investigated whether the presence and characteristics of a family
      caregiver affect the use of formal long-term care under the new Korean long-term
      care system. BACKGROUND: In July 2008, Korea introduced public long-term care
      insurance, a form of social insurance, in order to cope with the reality of the
      growing elderly population and the increasing demand for long-term care. METHODS:
      The family caregivers of 271 applicants for long-term care insurance who had a
      caregiver and 36 applicants without a caregiver living in one city participated
      in this cross-sectional study. Data were collected from November 2010 to June
      2011 using self-report questionnaires. Variables included the applicant's gender;
      age; physical and cognitive function; type of long-term care used; presence and
      type of family caregivers; caregiver's gender, age, education level, marital
      status, and employment status; and service use covered by long-term care
      insurance. Logistic multiple regression was used. RESULTS: The effect of the
      presence and characteristics of a family caregiver on the use of a long-term care
      facility was significant. A nursing home was used for care more frequently when
      the applicant had no family caregiver. An elderly subject who had a spouse as a
      caregiver used home healthcare services more often than nursing home services.
      CONCLUSION: The decision to use formal services may depend not only on the care
      level required by the applicant, but also on the presence and type of caregivers.
      To successfully implement the new long-term care insurance system, consideration
      of the caregiver situation should be included in policy development.

PMID- 24111854
TI  - Role of 3D animation in periodontal patient education: a randomized controlled
      trial.
AB  - AIM: This randomized controlled parallel trial investigates the effect of 3D
      animation on the increase and recall of knowledge on periodontitis by patients
      with periodontitis. The effects of a 3D animation (3D animation group) were
      compared with narration and drawing (control group) for periodontal patient
      education. MATERIAL AND METHODS: A total of 68 periodontitis patients were
      stratified according to educational level and then randomly allocated to control
      or 3D animation groups. All patients received: (1) a pre-test (baseline
      knowledge), (2) a patient education video (3D animation or control video), (3) a
      post-test (knowledge immediately after looking at the video), and (4) a follow-up
      test (knowledge recall after 2 weeks). Each test contained 10 multiple-choice
      questions. RESULTS: There was no significant difference in baseline knowledge.
      Patients receiving the 3D animations had significantly higher scores for both the
      post-test and the follow-up test, when compared with patients receiving sketch
      animations. CONCLUSION: 3D animations are more effective than real-time drawings
      for periodontal patient education in terms of knowledge recall. 3D animations may
      be a powerful tool for assisting in the information process.

PMID- 24111855
TI  - Uncertainty in climate change modeling: can global sensitivity analysis be of
      help?
AB  - Integrated assessment models offer a crucial support to decisionmakers in climate
      policy making. For a full understanding and corroboration of model results,
      analysts ought to identify the exogenous variables that influence the model
      results the most (key drivers), appraise the relevance of interactions, and the
      direction of change associated with the simultaneous variation of uncertain
      variables. We show that such information can be directly extracted from the data
      set produced by Monte Carlo simulations. Our discussion is guided by the
      application to the well-known DICE model of William Nordhaus. The proposed
      methodology allows analysts to draw robust insights into the dependence of future
      atmospheric temperature, global emissions, and carbon costs and taxes on the
      model's exogenous variables. 

PMID- 24111856
TI  - The apoptotic and proliferation rate of tumour budding cells in colorectal cancer
      outlines a heterogeneous population of cells with various impacts on clinical
      outcome.
AB  - AIMS: In colorectal cancer (CRC), tumour buds represent an aggressive cell type
      at the invasive front with apparently low proliferation. The aim of this study
      was to determine proliferation and apoptotic rates of buds in comparison to
      tumour centre, front and mucosa. METHODS AND RESULTS: Whole tissue sections from
      188 CRC patients underwent immunohistochemistry for Ki67. Ten high-power fields
      (HPFs) were evaluated in mucosa, tumour centre, tumour front and tumour buds
      (total = 40 HPFs/case). Caspase-3 and M30 immunohistochemistry were performed on
      a multipunch tissue microarray from the same cohort. Ki67, caspase-3 and M30
      immunoreactivity were correlated with outcome. The average percentage of cells
      showing Ki67 positivity was 5.2% in mucosa, and was not significantly different
      between the centre and front of the tumour (38.2% and 34.9%; P < 0.0001); 0.3% of
      buds showed Ki67 positivity (P < 0.0001). Caspase-3 expression was similar in
      mucosa, tumour centre and tumour front, but lower in tumour buds (<0.1%; P <
      0.0001). M30 staining in buds was decreased (0.01%; P < 0.0001) in comparison to
      other areas. Ki67 positivity in buds was detrimental to survival in univariate (P
      = 0.0352) and multivariate (P = 0.0355) analysis. Caspase-3-positive tumours
      showed better outcome than negative tumours (P = 0.0262); but tumours with
      caspase-3-positive buds showed a worse outcome than those with caspase-3-negative
      buds (P = 0.0235). CONCLUSIONS: Ki67, caspase-3 and M30 staining is absent in
      most tumour buds, suggesting decreased proliferation and apoptosis. However, the
      fact that Ki67 and caspase-3 immunoreactivity was associated with unfavourable
      prognosis points to a heterogeneous population of tumour buds.

PMID- 24111857
TI  - Fluorogenic alpha-tocopherol analogue for monitoring the antioxidant status
      within the inner mitochondrial membrane of live cells.
AB  - We report here the preparation of a lipophilic fluorogenic antioxidant (Mito
      Bodipy-TOH) that targets the inner mitochondrial lipid membrane (IMM) and is
      sensitive to the presence of lipid peroxyl radicals, effective chain carriers in
      the lipid chain autoxidation. Mito-Bodipy-TOH enables monitoring of the
      antioxidant status, i.e., the antioxidant load and ability to prevent lipid chain
      autoxidation, within the inner mitochondrial membrane of live cells. The new
      probe consists of 3 segments: a receptor, a reporter, and a mitochondria
      targeting element, constructed, respectively, from an alpha-tocopherol-like
      chromanol moiety, a BODIPY fluorophore, and a triphenylphosphonium cation (TPP).
      The chromanol moiety ensures reactivity akin to that of alpha-tocopherol, the
      most potent naturally occurring lipid soluble antioxidant, while the BODIPY
      fluorophore and TPP ensure partitioning within the inner mitochondrial membrane.
      Mechanistic studies conducted either in homogeneous solution or in liposomes and
      in the presence of free radical initiators show that the antioxidant activity of
      Mito-Bodipy-TOH is on par with that of alpha-tocopherol. Studies conducted on
      live fibroblast cells further show the antioxidant depletion in the presence of
      methyl viologen (paraquat), a known agent of oxidative stress and source of
      superoxide radical anion (and indirectly, a causative of lipid peroxidation)
      within the mitochondria matrix. We recorded a ca. 8-fold emission enhancement
      with Mito-Bodipy-TOH in cells stressed with methyl viologen, whereas no
      enhancement was observed in control studies with untreated cells. Our findings
      underscore the potential of the new fluorogenic antioxidant Mito-Bodipy-TOH to
      study the chemical link between antioxidant load, lipid peroxidation and
      mitochondrial physiology. 

PMID- 24111858
TI  - Bilateral Concordance of the Fundus Hyperautofluorescent Ring in Typical
      Retinitis Pigmentosa Patients.
AB  - BACKGROUND: It has long been assumed that in retinitis pigmentosa, disease
      presentation and progression are symmetrical. This study investigated whether
      hyperautofluorescent ring size, one known marker of disease progression, is
      symmetrical in typical RP patients. MATERIALS AND METHODS: A total of 88 patients
      with typical retinitis pigmentosa were enrolled in the study. Each presented with
      a hyperautofluorescent ring when imaged at baseline with fundus autofluorescence
      (AF). Vertical and horizontal diameters were analyzed according to mode of
      inheritance and age group. Seven of 88 patients had data missing in one eye and
      were excluded from further analysis. RESULTS: There was no significant
      relationship between hyperautofluorescent ring diameter and inheritance mode.
      There was a tendency toward smaller ring size with age and 3.7% of subjects
      displayed marked asymmetry in ring size between right and left eyes, although
      their electroretinogram results did not differ. Overall, when patients were
      considered as a group, there was a high correlation between right and left eyes'
      horizontal and vertical diameters (r=0.99, p<0.0001; r=0.98, p<0.0001). Comparing
      individual patients' eyes, and accounting for measurement error, a smaller
      majority of patients displayed symmetry of the hyperautofluorescent ring in both
      dimensions (85.7% in the vertical dimension, 87.3% in the horizontal dimension).
      CONCLUSION: This study confirmed the highly symmetrical nature of the
      hyperautofluorescent ring in RP patients, except in a small subgroup. AF results,
      which provide less variability per image, and are consistently interpreted
      between different observers, may be a more sensitive and reliable method for
      testing symmetry than many functional tests.

PMID- 24111859
TI  - Exploring HIV-testing intentions in young Asian/Pacific Islander (API) women as
      it relates to acculturation, theory of gender and power (TGP), and the AIDS risk
      reduction model (ARRM).
AB  - While HIV rates are low for Asian/Pacific Islanders (APIs), they have been
      increasing, especially for API women in the USA. We conducted a cross-sectional
      study with 299 young API women (18-24 years old) in the Inland Empire region of
      Southern California to better understand their intention for HIV testing and
      their perceptions about HIV/AIDS. Data analyses included descriptive statistics,
      bivariate exploration for model building and multivariate analyses to determine
      variables associated with HIV-testing intentions. Results suggest that more
      lifetime sexual partners, greater perceived gender susceptibility, higher
      HIV/AIDS knowledge, sexually active, more positive attitudes about HIV testing
      and higher self-perceptions/experiences related to risk contribute to stronger
      intentions for HIV testing in young API women. Findings from this study will
      contribute to the limited literature on HIV/AIDS in API women and provide
      information that can be used for developing and implementing culturally
      appropriate programs that encourage HIV prevention and testing in this
      population. 

PMID- 24111860
TI  - Incretin-based therapies: facing the realities of benefits versus side effects.

PMID- 24111861
TI  - Postprandial glycemic control conditions in relation to urinary N-acetyl-beta-D
      glucosaminidase in patients with type 2 diabetes mellitus without low glomerular
      filtration rate.
AB  - BACKGROUND: This study assessed the relationship between the serum level of 1,5
      anhydroglucitol (1,5-AG), a marker of postprandial hyperglycemia, and the ratio
      of the urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) to creatinine
      (NAG index) in patients with type 2 diabetes mellitus. SUBJECTS AND METHODS: This
      was a cross-sectional study with 153 patients who had an estimated glomerular
      filtration rate of >=60 mL/min/1.73 m(2) and no proteinuria and who had never
      been treated with oral hypoglycemic agents or insulin. On the basis of 1,5-AG
      levels, the patients were divided into a High 1,5-AG group (>14.0 MUg/mL) and a
      Low 1,5-AG group (<=14.0 MUg/mL). RESULTS: The logarithmically transformed NAG
      index was significantly higher in the Low 1,5-AG group than in the High 1,5-AG
      group when all glycated hemoglobin (HbA1c) levels were included. The
      logarithmically transformed NAG index was lowest in the High 1,5-AG group with an
      HbA1c level of <=6.4% and was highest in the Low 1,5-AG group with an HbA1c level
      of >=7.5%. Multivariate regression analysis showed that the NAG index had a
      higher independent association with 1,5-AG than with HbA1c or the fasting plasma
      glucose level. In all models, multivariate regression analyses showed that the
      NAG index was correlated with age. CONCLUSIONS: These results suggest that
      postprandial hyperglycemia correlates with early renal tubule injury in type 2
      diabetes mellitus.

PMID- 24111862
TI  - Human cartilage chitinase 3-like protein 2: cloning, expression, and production
      of polyclonal and monoclonal antibodies for osteoarthritis detection and
      identification of potential binding partners.
AB  - Human cartilage chitinase 3-like protein 2 (CHI3L2 or YKL-39) is a member of
      family-18 glycosyl hydrolases that lacks chitinase activity. YKL-39 is known as a
      potential marker for the activation of chondrocytes and the progression of
      osteoarthritis. In this study, we cloned and expressed a functional form of human
      YKL-39 in the bacterial system. The Escherichia coli expressed YKL-30 was used as
      immugen for production of anti YKL-39 polyclonal and monoclonal antibodies. Both
      antibody types were highly selective, reacting only with YKL-39. Isotype mapping
      identified two hybridoma clones (so called clones 6H11 and 8H3) to be IgM
      isotype. Dot blot assay showed that the monoclonal antibody was strongly active
      with the synovial fluid of an osteoarthritis patient, human monocyte, and T
      lymphocyte cell lines. Database search for protein binding partners gave high
      hits with several glycoproteins that play particular roles in cartilage tissue
      scaffolding, connective tissue formation, and cell-cell interactions. In
      conclusion, anti YKL-39 polyclonal and monoclonal antibodies were raised and
      tested to be suitable for immunological applications, such as the investigation
      of the YKL-39 regulating pathway and the development of an immunosensing tool for
      sensitive detection of cartilage tissue destruction. 

PMID- 24111863
TI  - Screening and antiviral analysis of phages that display peptides with an affinity
      to subunit C of porcine aminopeptidase.
AB  - The purified C subunit of the recombinant porcine aminopeptidase N (rpAPN-C)
      protein was used as an immobilized target to screen potential ligands against
      rpAPN-C from a 12-mer phage display random peptide library. After five rounds of
      biopanning, five phage clones showed specific binding affinities to rpAPN-C. In 3
      (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays, the
      phage clone PM1, which contained the HDAISWTHYHPW peptide sequence, had a
      protective effect against TGEV infection in swine testis cells. Therefore, the
      HDAISWTHYHPW peptide sequence has a potential use as a small molecular
      therapeutic agent against TGEV infection. 

PMID- 24111864
TI  - Monoclonal antibodies specific to Streptococcus mutans GS-5 glucosyltransferase-C
      inhibit bacterial glucosyltransferase.
AB  - Glucosyltransferase-C (GTFC) is a virulence factor of Streptococcus mutans.
      Additionally, GTFC represents an essential element required for bacterial cell
      coherence, allowing for the formation of dental plaque, which leads to dental
      caries. As such, monoclonal antibodies (MAbs) against S. mutans are believed to
      offer some protection against dental caries. In the current study, we amplified
      an approximately 1.5 kb fragment of the N-terminal half of the S. mutans gtfC
      gene by PCR, then induced expression of this gene. This protein was designated
      GTFCN. After the expressed protein was purified, it was used as an immunogen and
      injected into BALB/c mice. We selected and established two MAbs by producing
      hybridomas (HCN17 and HCN37). The anti-GTFCN antibody isotype was confirmed as
      IgG2a for HCN17 and IgG2b for HCN37. The anti-GTFCN antibody was found to
      specifically react with the GTFCN protein. The enzymatic activity of the crude
      glucosyltransferase of S. mutans GS-5 was significantly inhibited at a
      concentration of 350 ng of MAb/mL. These results suggest that the monoclonal anti
      GTFCN antibodies could represent an alternative modality for passive immunization
      to prevent S. mutans aggregation and dental plaque.

PMID- 24111865
TI  - Rapid detection of S. mutans surface antigen I/II using a sensitive monoclonal
      anti-Ag I/II antibody by ELISA.
AB  - The cell-surface protein antigen I/II (Ag I/II) is expressed in oral
      streptococci, which are known as the causative agent of a number of diseases
      including dental caries, endocarditis, gingivitis, and periodontal disease.
      Consequently, monoclonal antibodies (MAb) capable of recognizing the
      streptococcal Ag I/II protein could be a useful tool for the diagnosis and cure
      of these diseases. In this study, a previously generated monoclonal anti-Ag I/II
      antibody, ckAg I/II, was used to detect a small amount of Streptococcus mutans
      (S. mutans) surface antigen Ag I/II. The ckAg I/II was proved to be very
      sensitive and able to detect as little as 1 ng of recombinant Ag I/II protein
      within 5 min and Ag I/II in saliva within 10 min, as well as native Ag I/II in 20
      MUL of culture supernatant by ELISA. These results suggest that ckAg I/II can be
      used as a fast and efficient diagnostic tool to detect Ag I/II.

PMID- 24111866
TI  - Development, purification, and characterization of monoclonal antibodies against
      recombinant histidine-rich protein 3 of Plasmodium falciparum.
AB  - In the present study, monoclonal antibodies (MAbs) against recombinant histidine
      rich protein (rHRP3) were developed and assessed for their potential in detection
      of Plasmodium falciparum HRP3. Hybridomas were obtained by fusion of Sp2/0 mouse
      myeloma cells and spleen cells from the mouse immunized with purified rHRP3.
      Three MAbs (IgG1 isotype) specific to rHRP3 were established and characterized by
      enzyme-linked immunosorbent assay (ELISA) and immunoblotting for sensitivity and
      specificity. Purification of MAbs from hybridoma cell culture supernatant and
      PAbs from rabbit anti-serum were carried out using Phenylpropylamine (PPA)
      HyperCel(TM) sorbent. The MAbs were able to detect rHRP3 and the HRP3 from P.
      falciparum spent medium. Sandwich ELISA was developed to quantify HRP3 in the
      spent medium of P. falciparum culture. The generated MAbs could be potentially
      used in immuno-based diagnostic systems for the detection of P. falciparum HRP. 

PMID- 24111867
TI  - Preparation and identification of a novel antibody against human CDC7 kinase.
AB  - Cell division cycle 7-related protein kinase (CDC7), which is conservatively
      expressed in the eukaryotic cells, is being intensely studied because of its
      significant function in DNA replication. In order to get further information on
      human CDC7, we generated a novel antibody against human CDC7. The steady strain
      of hybridoma (2G12) that can secrete specific monoclonal antibodies against human
      CDC7 was obtained by hybridoma technique. It is poised to contribute novel ways
      to study the cell cycle. The isotope of the monoclonal antibody was tested to be
      IgG2a/kappa, and its characterizations were shown by enzyme-linked immunosorbent
      assay (ELISA) and Western blot analysis. The affinity constant (Kaff) of the
      monoclonal antibody was measured by non-competitive ELISA. By Western blot
      analysis, we found that CDC7 was largely expressed on the HCCLM3 cell line.
      Further identifications were adopted by the HRP-labeled MAbs. Thus, the antibody
      might boost studies on tumor cell lines.

PMID- 24111868
TI  - A monoclonal antibody against the human SUMO-1 protein obtained by immunization
      with recombinant protein and CpG-DNA-liposome complex.
AB  - Post-translational modification regulated by conjugation of a small ubiquitin
      like modifier (SUMO) is involved in various cellular processes. In this study, we
      expressed and purified recombinant human SUMO-1 (hSUMO-1). BALB/c mice were
      immunized with a complex of hSUMO-1 protein and Lipoplex(O) to produce hSUMO-1
      specific antibodies. Using conventional hybridoma technology, we obtained four
      hybridoma clones derived from the mouse with the highest antibody titer against
      hSUMO-1. Based on Western blot analysis, our hSUMO-1 monoclonal antibody
      specifically recognizes hSUMO-1, but not other SUMO proteins. These results
      support that the anti-hSUMO-1 monoclonal antibody produced with the aid of
      Lipoplex(O) adjuvant is specific and that Lipoplex(O) is useful for development
      of monoclonal antibodies against recombinant protein. In addition, we analyzed
      human tissues to examine the distribution of hSUMO-1. Higher expression of hSUMO
      1 was detected in normal adrenal gland, esophagus, pancreas, liver, stomach,
      kidney, and uterus than in corresponding cancer tissues, suggesting a tumor
      suppressive function of hSUMO-1. 

PMID- 24111869
TI  - Monoclonal antibodies against Nsp2 protein of the highly pathogenic porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) continues to be a serious
      threat, causing an economically significant impact on the swine industry
      worldwide. In this study, non-structural protein Nsp2 of porcine reproductive and
      respiratory syndrome virus (PRRSV) was expressed in Escherichia coli and purified
      by dialysis. An important monoclonal antibody (MAb 2H6) against Nsp2 protein was
      generated by fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from
      Nsp2 protein immunized mice. Then activity of the MAb was characterized by enzyme
      linked immunosorbent assay (ELISA), Western blot analysis, and indirect
      immunofluorescence assays. The results demonstrated that the MAb has a positive
      reaction to HP-PRRSV in IFA at 1:100 dilution and in Western blot analysis at
      1:500 dilution, and no reaction with classic PRRSV. These indicated that this MAb
      against Nsp2 protein of PRRSV might be a good candidate for a specific diagnostic
      method and functional exploration of the Nsp2 protein. 

PMID- 24111870
TI  - A sandwich enzyme-linked immunosorbent assay for detection of calreticulin in
      human serum.
AB  - Calreticulin (CRT) is a 46 kDa Ca(2+) binding chaperone protein that is mainly
      located in the endoplasmic reticulum luminal and has various biological
      functions. It is important to establish a specific and sensitive CRT enzyme
      linked immunosorbent assay (ELISA) for the study of CRT functions. Therefore, we
      prepared a polyclonal antibody (PAb) in rabbits immunized with a recombinant CRT
      protein. Based on the PAb and our previously prepared monoclonal antibody (MAb),
      a highly specific and sensitive ELISA was developed. In the present study, we
      describe a sandwich ELISA for the determination of CRT protein in human serum. It
      was found that soluble CRT (sCRT) concentration in serum samples from 49 lung
      cancer patients was significantly higher than that from 53 healthy individuals
      (p=0.004). This result demonstrates that sCRT concentration in sera of lung
      cancer patients is higher than that in sera of healthy individuals. In
      conclusion, the prepared CRT antibodies and developed ELISA is a potential tool
      for CRT research and offers an alternative, simple, rapid technique for detecting
      CRT, especially in large ongoing and future clinical studies.

PMID- 24111871
TI  - Generation of a monoclonal antibody to S1 protein of porcine epidemic diarrhea
      virus.
AB  - Gene encoding the N-terminal half of spike protein (S1) of porcine epidemic
      diarrhea virus (PEDV) was cloned and expressed as a recombinant protein in
      Escherichia coli BL21 (DE3). Then, female BALB/c mice were immunized with the
      purified recombinant S1 protein (rS1), and a monoclonal antibody (MAb designated
      as 5E12) against the rS1 protein was achieved by hybridoma technique. MAb 5E12
      not only reacted with rS1 protein indirect ELISA and Western blot, but also
      recognized PEDV transiently expressed in Vero E6 cells in indirect
      immunofluorescence examinations. This work suggests that 5E12 would be a useful
      tool as a specific diagnostic reagent for detecting PEDV S protein. 

PMID- 24111874
TI  - What constitutes cerebral palsy in the twenty-first century?
AB  - AIM: Determining inclusion/exclusion criteria for cerebral palsy (CP)
      surveillance is challenging. The aims of this paper were to (1) define
      inclusion/exclusion criteria that have been adopted uniformly by surveillance
      programmes and identify where consensus is still elusive, and (2) provide an
      updated list of the consensus concerning CP inclusion/exclusion when a
      syndrome/disorder is diagnosed. METHOD: Data were drawn from an international
      survey of CP registers, the New South Wales CP Register (1993-2003), the Western
      Australian CP Register (1975-2008), and the Surveillance of CP in Europe (SCPE;
      1976-1998). An expert panel used a consensus building technique, which utilized
      the SCPE 'decision tree' and the original 'What constitutes cerebral palsy?'
      paper as frameworks. RESULTS: CP surveillance programmes agree on key clinical
      criteria pertaining to the type, severity, and origin of motor disorder in CP.
      Further work is warranted to reach agreement for (1) minimum age of survival and
      maximum age of postneonatal brain injury, and (2) metabolic disorders with highly
      variable clinical courses/responses to treatment. One hundred and ninety-seven
      syndromes/disorders were reviewed and advice on their inclusion/exclusion is
      provided. INTERPRETATION: What constitutes CP will continue to evolve as
      diagnostics improve. Surveillance programmes throughout the world are committed
      to addressing their differences regarding inclusion/exclusion criteria for the
      umbrella term CP.

PMID- 24111875
TI  - Feeding the heat on brown fat.
AB  - Nutrition plays a dominant role in human adaptation. Biological traits conferring
      these adaptations are of considerable significance. Within an obesogenic
      environment, there is considerable variation among individuals in their
      susceptibility to weight gain. Some individuals rapidly gain weight, whereas
      others remain lean without any conscious effort, suggesting that obesity
      pathogenesis may not be centered on just the primal feeding behavior. The ability
      of certain individuals to subconsciously resist obesity reveals adaptive calorie
      burning mechanisms that may promote fitness. Here, we review a fat-burning
      mechanism that is turned on by the brain hormone orexin during high-caloric food
      consumption. Remarkably, the same hormone also induces feeding, and its levels
      correlate with lean body mass in both rodents and humans. Intriguingly, loss of
      orexin prevents thermogenic energy expenditure while inducing obesity in the face
      of hypophagia. Thus, orexin is a unique neuropeptide that promotes both feeding
      and energy expenditure, conferring resistance to weight gain. Mechanisms that
      safely augment orexin signaling may have potential in antiobesity therapeutics. 

PMID- 24111876
TI  - Potent inhibition of the C-P lyase nucleosidase PhnI by Immucillin-A
      triphosphate.
AB  - The C-P lyase complex in bacteria catalyzes the transformation of phosphonates to
      orthophosphate under conditions of phosphate starvation. The first committed step
      in the C-P lyase-catalyzed reaction is the displacement of adenine from MgATP by
      phosphonate substrates, yielding ribose-1-phosphonate-5-triphosphate. In the C-P
      lyase complex, this reaction is catalyzed by the nucleosidase PhnI and modulated
      by the addition of PhnG, PhnH, and PhnL. Here we describe the synthesis of
      Immucillin-A triphosphate, a mimic of the transition state structure for the
      nucleosidase reaction catalyzed by PhnI. This compound inhibits PhnI with a
      dissociation constant of 20 nM at pH 7.5. 

PMID- 24111877
TI  - MicroRNA target identification: lessons from hypoxamiRs.
AB  - SIGNIFICANCE: MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as
      key regulators of many physiological and pathological processes, including those
      relevant to hypoxia such as cancer, neurological dysfunctions, myocardial
      infarction, and lung diseases. RECENT ADVANCES: During the last 5 years, miRNAs
      have been shown to play a role in the regulation of the cellular response to
      hypoxia. The identification of several bona fide targets of these hypoxamiRs has
      underlined their pleiotropic functions and the complexity of the molecular rules
      directing miRNA::target transcript pairing. CRITICAL ISSUES: This review outlines
      the main in silico and experimental approaches used to identify the targetome of
      hypoxamiRs and presents new recent relevant methodologies for future studies.
      FUTURE DIRECTIONS: Since hypoxia plays key roles in many pathophysiological
      conditions, the precise characterization of regulatory hypoxamiRs networks will
      be instrumental both at a fundamental level and for their future potential
      therapeutic applications.

PMID- 24111878
TI  - Co-morbidities and hyperinflation are independent risk factors of all-cause
      mortality in very severe COPD.
AB  - BACKGROUND: COPD is a multi-component disease that is not sufficiently reflected
      by FEV1 alone. We studied in patients with very severe COPD, which dimensions of
      the disease, including co-morbidities, dominate prognosis. METHODS: In patients
      with FEV1 < 30% predicted, anthropometric, laboratory, spirometric and body
      plethysmographic data, smoking status, alcohol consumption, the level of dyspnoea
      and exercise performance were assessed. Co-morbidities were categorized by the
      Charlson-index and the COPD-specific co-morbidity test (COTE). The prognostic
      value of multiple dimensions was explored using uni- and multivariate survival
      analyses regarding death from any or respiratory cause. RESULTS: Among 209
      patients included (58/151 female/male; FEV1 25.0 (22.0-26.9)%predicted), arterial
      hypertension (54.1%), hyperlipidemia (38.3%) and diabetes (19.6%) were most
      common, 57.9% showing a COTE-index of >= 1 point. During follow-up (28 (14-45)
      months), 121 patients had died, mostly (56.2%) due to respiratory causes. Age,
      BMI, the ratio of residual volume to total lung capacity (RV/TLC), co-morbidities
      in terms of the COTE- and Charlson-index, but not FEV1, were significantly
      associated with all-cause and respiratory mortality. The association of the
      median values of the Charlson- (HR 1.911 [95%-CI 1.338-2.730]) and COTE-index (HR
      1.852 [95%-CI 1.297-2.644], p < 0.001 each) with mortality was similar and
      stronger when combined with age. In multivariate analyses, only RV/TLC and co
      morbidities were independent risk factors of all-cause mortality (p < 0.05 each).
      CONCLUSION: In very severe COPD, resting hyperinflation and co-morbidities
      provide the major prognostic information, whereas the association of the recently
      introduced COTE-index with mortality was similar to that of the established
      Charlson-index and even stronger when including age.

PMID- 24111879
TI  - The inner ear of Megatherium and the evolution of the vestibular system in
      sloths.
AB  - Extant tree sloths are uniquely slow mammals with a very specialized suspensory
      behavior. To improve our understanding of their peculiar evolution, we
      investigated the inner ear morphology of one of the largest and most popular
      fossil ground sloths, Megatherium americanum. We first address the predicted
      agility of this animal from the scaling of its semicircular canals (SC) relative
      to body mass, based on recent work that provided evidence that the size of the SC
      in mammals correlates with body mass and levels of agility. Our analyses predict
      intermediate levels of agility for Megatherium, contrasting with the extreme
      slowness of extant sloths. Secondly, we focus on the morphology of the SC at the
      inner ear scale and investigate the shape and proportions of these structures in
      Megatherium and in a large diversity of extant xenarthrans represented in our
      database. Our morphometric analyses demonstrate that the giant ground sloth
      clearly departs from the SC morphology of both extant sloth genera (Choloepus,
      Bradypus) and is in some aspects closer to that of armadillos and anteaters.
      Given the close phylogenetic relationships of Megatherium with the extant genus
      Choloepus, these results are evidence of substantial homoplasy of the SC anatomy
      in sloths. This homoplasy most likely corresponds to an outstanding convergent
      evolution between extant suspensory sloth genera. 

PMID- 24111881
TI  - Viewing the MMPI-2-RF structure through the Personality Psychopathology Five (PSY
      5) lens.
AB  - Ben-Porath and Tellegen (2008) recommend organizing MMPI-2-RF scale interpretive
      information around 3 broad topics, emotional/internalizing dysfunction, thought
      dysfunction, and externalizing/behavioral dysfunction, and 3 additional topics
      labeled somatic complaints, interpersonal functioning, and interests. That
      organization is based primarily on structural analyses of the Restructured
      Clinical (RC) scales. This study reviewed the MMPI-2-RF's scale structure when
      the Personality Psychopathology Five (PSY-5) scales are included. Principal axis
      factor analyses with oblique rotation were conducted on the Restructured
      Clinical, PSY-5, and Special Problem (SP) scales in 2 samples, by gender. One
      sample was an outpatient community health center, the other a large, metropolitan
      inpatient psychiatric facility. The 6-factor solution evidenced each of the PSY-5
      constructs plus a general somatic concerns factor. Implications of this solution
      in comparison to the 3-factor organizing structure recommended by Ben-Porath and
      Tellegen are discussed. 

PMID- 24111880
TI  - The impact of skin damage due to cutaneous lupus on quality of life.
AB  - BACKGROUND: Patients with more severe cutaneous lupus erythematosus (CLE) have a
      poorer quality of life (QoL). Racial and ethnic disparities have been reported in
      disease activity and outcomes in systemic lupus erythematosus, but similar
      information is not available for CLE. OBJECTIVES: To evaluate the impact of lupus
      related skin damage on skin-specific QoL, and to analyse differences stratified
      by ethnic background. METHODS: Data collected included sex, race, diagnosis and
      Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Skindex
      29 scores. These parameters were analysed at the initial and last visits. CLASI
      damage scores (dyspigmentation and scarring) and activity scores were collected,
      grouped by ethnicity, and correlated with Skindex-29. Overall, 223 patients were
      analysed at baseline, with 141 completing more than one study visit. RESULTS: The
      majority of patients were white (63.7%), followed by African American (29.1%) and
      Asian American (4.0%). African American patients accounted for a disproportionate
      percentage of both localized (50%) and generalized discoid lupus erythematosus
      (DLE) (49%). Median CLASI damage scores differed significantly between the
      African American, white and Asian American patients, at both the first (8.5, 4.0,
      7.0, respectively; P < 0.0001) and last visit (10.0, 6.0, 8.5, respectively; P <
      0.01). CLASI damage scores in African Americans correlated with CLASI activity
      scores (Spearman r = 0.45, P = 0.0003). CONCLUSIONS: There was no significant
      correlation between CLASI damage scores and Skindex domains overall.
      Individually, dyspigmentation and scarring also did not have a significant effect
      on QoL. Ethnic differences in patients with CLE were found: African American
      patients exhibited a high rate of DLE and experienced damage early in their
      disease course, frequently in conjunction with disease activity.

PMID- 24111882
TI  - Ab initio intermolecular potential of Ar-C2H2 refined using high-resolution
      spectroscopic data.
AB  - The high-resolution infrared spectra of the nu1 + nu3 (2CH) band of the Ar-C2H2
      complex has been recorded from 6544 to 6566 cm(-1). The previously reported K(a)
      = 1 <- 0, 2 <- 1, and 0 <- 1 subbands were observed and the K(a) = 1 <- 2, 2 <-
      3, and 3 <- 2 subbands were assigned for the first time. The intermolecular
      potential energy surface of this complex has been calculated ab initio and
      optimized by fitting the new high-resolution data. Refined intermolecular
      potential energy surfaces have been obtained for the ground vibrational state and
      for the excited v1 = v3 = 1 stretching state. For the former state, the results
      of the analysis are satisfactory and the microwave transitions of the complex are
      reproduced with a root-mean-square deviation of 5 MHz. For the latter state,
      systematic discrepancies arise in the analysis.

PMID- 24111883
TI  - Capecitabine-induced subacute cutaneous lupus erythematosus: report of a case
      with positive rechallenge test.

PMID- 24111884
TI  - Is somatic health screening in patients with severe mental illness of added
      value?
AB  - PURPOSE: To evaluate the added value of somatic screening for patients with
      severe mental illness over regular care. DESIGN AND METHODS: We compared the
      information on somatic health problems collected by screening with the general
      practitioner (GP) files (n = 118). FINDINGS: The mean number of somatic health
      problems detected with somatic health screening was significantly higher than
      those noted in GP records (p < .01). PRACTICE IMPLICATIONS: Somatic health
      screening is an addition to the care provided by the GP. Advanced mental health
      nurses can play a key role in somatic health screening and initiating further
      cooperation and communication of GP and mental health care.

PMID- 24111885
TI  - Exploiting pseudo C2-symmetry for an efficient synthesis of the F-ring of the
      spongistatins.
AB  - A concise and efficient synthesis of the F-ring fragment of the potent
      antimitotic marine macrolide spongistatin 1 has been developed. The key sequence
      involves double cross-metathesis/Sharpless asymmetric dihydroxylation reactions
      to establish four stereocenters in a pseudo C2-symmetric array, followed by a
      selective protection reaction that breaks the pseudosymmetry, establishes a fifth
      stereocenter, and effectively differentiates the ester termini. Overall, the six
      contiguous stereocenters in the C(37)-C(45) F-ring fragment are established in
      just seven steps. 

PMID- 24111887
TI  - Nanostructured lipid carriers as a delivery system of biochanin A.
AB  - The aim of this study was to explore the nanostructured lipid carriers as a
      delivery system of biochanin A so as to supply a method to improve its
      bioavailability. Biochanin A-loaded nanostructured lipid carriers (BCA-NLCs) were
      prepared by the method of emulsion-evaporation and low temperature
      solidification. Pharmacokinetics was carried out in rats upon oral administration
      at a dose of 10 mg/kg. BCA-NLC showed spherical formulation and had mean diameter
      174.68+/-0.96 nm, zeta potential -20.9+/-0.8 mv and entrapment efficiency 97.36+/
      0.14%. DSC and XRD studies indicated that BCA was not in crystal state in NLC. In
      in vitro release study, the BCA from BCA-NLC exhibited a biphasic release pattern
      with burst release initially and sustained release afterwards. BCA-NLC showed
      higher AUC value and circulated in blood for a longer time than BCA suspension.
      The studies demonstrated that NLC could be a potential delivery system for BCA to
      improve bioavailability.

PMID- 24111886
TI  - Treatment of periodontitis improves the atherosclerotic profile: a systematic
      review and meta-analysis.
AB  - AIM: Systematic review and meta-analyses to study the robustness of observations
      that treatment of periodontitis improves the atherosclerotic profile. MATERIAL
      AND METHODS: Literature was searched in Medline-PubMed, Cochrane CENTRAL and
      EMBASE, based on controlled periodontal intervention trials, including also a non
      intervention group. Data were extracted and meta-analyses were performed.
      RESULTS: From 3928 screened studies, 25 trials met the eligibility criteria.
      These trials enrolled 1748 periodontitis patients. Seven trials enrolled
      periodontitis patients that were otherwise healthy, 18 trials recruited
      periodontal patients with various co-morbidities, such as CVD or diabetes. None
      of the trials used hard clinical endpoints of CVD. However, improvement of
      endothelial function has been consistently reported. Meta-analyses demonstrated
      significant weighted mean difference (WMD) for hsCRP (-0.50 mg/l, 95% CI:-0.78; 
      0.22), IL-6 (-0.48 ng/l, 95% CI: -0.90; -0.06), TNF-alpha (-0.75 pg/ml, 95% CI: 
      1.34; -0.17), fibrinogen (-0.47 g/l, 95% CI: -0.76; -0.17), total cholesterol (
      0.11 mmol/l, 95% CI: -0.21; -0.01) and HDL-C (0.04 mmol/l, 95% CI: 0.03; 0.06)
      favouring periodontal intervention. Importantly, periodontitis patients with co
      morbidity benefitted most from periodontal therapy; significant WMD were observed
      for levels of hsCRP (-0.71 mg/l, 95% CI: -1.05; -0.36), IL-6 (-0.87 ng/l, 95% CI:
      -0.97; -0.78), triglycerides (-0.24 mmol/l, 95% CI: -0.26; -0.22), total
      cholesterol (-0.15 mmol/l, 95% CI: -0.29; -0.01), HDL-C (0.05 mmol/l, 95% CI:
      0.03; 0.06) and HbA1c (-0.43%, 95% CI: -0.60; -0.25). CONCLUSIONS: This
      systematic review and meta-analyses demonstrate that periodontal treatment
      improves endothelial function and reduces biomarkers of atherosclerotic disease,
      especially in those already suffering from CVD and/or diabetes.

PMID- 24111888
TI  - alpha7-nicotinic acetylcholine receptor agonists for cognitive enhancement in
      schizophrenia.
AB  - alpha7-Nicotinic acetylcholine receptors have emerged as a potential therapeutic
      target for the treatment of neurocognitive dysfunctions in schizophrenia that are
      often resistant to existing antipsychotic drugs. Molecular evidence for
      involvement in schizophrenia of CHRNA7, the gene for the receptor subunit, in the
      neurobiology of deficits in attention is a critical rationale for the clinical
      study of alpha7-nicotinic receptor agonists to improve neurocognition. Initial
      clinical trials show enhancement of inhibitory neuron function related to sensory
      gating and increased attention and working memory, as well as improvement in
      negative symptoms such as anhedonia and alogia. Further development of this
      therapeutic strategy requires assessment of interactions with patients' heavy
      cigarette smoking and the relationship of this mechanism to the therapeutic
      effects of clozapine and olanzapine, both highly effective therapeutics with
      significant side effects. 

PMID- 24111890
TI  - Delivering value: provider efforts to improve the quality and reduce the cost of
      health care.
AB  - Growing concern regarding costs of care and health outcomes in the United States
      has led to widespread calls to address the issue of health care spending. Today,
      providers across the country are working both to improve the quality and to
      reduce the cost of health care. These activities span multiple care delivery
      settings and include care standardization and redesign, shared decision making,
      palliative care, care coordination, readmission reduction, patient engagement,
      predictive modeling, and direct cost reduction. These efforts differ from those
      undertaken in the past because of the availability of information technology
      tools to collect and analyze data, and because of the emphasis on cost reduction
      in conjunction with quality improvement. Although the available literature
      reflects only a small fraction of the provider activities currently in progress,
      there is cause for hope for achieving a sustainable, innovative, and value-driven
      health care system. 

PMID- 24111889
TI  - Applied pharmacogenomics in cardiovascular medicine.
AB  - Interindividual heterogeneity in drug response is a central feature of all drug
      therapies. Studies in individual patients, families, and populations over the
      past several decades have identified variants in genes encoding drug elimination
      or drug target pathways that in some cases contribute substantially to variable
      efficacy and toxicity. Important associations of pharmacogenomics in
      cardiovascular medicine include clopidogrel and risk for in-stent thrombosis,
      steady-state warfarin dose, myotoxicity with simvastatin, and certain drug
      induced arrhythmias. This review describes methods used to accumulate and
      validate these findings and points to approaches--now being put in place at some
      centers--to implementing them in clinical care.

PMID- 24111891
TI  - Male circumcision: a globally relevant but under-utilized method for the
      prevention of HIV and other sexually transmitted infections.
AB  - Randomized trials have demonstrated that male circumcision (MC) reduces
      heterosexual acquisition of HIV, herpes simplex virus type 2, human
      papillomavirus (HPV), and genital ulcer disease among men, and it reduces HPV,
      genital ulcer disease, bacterial vaginosis, and trichomoniasis among female
      partners. The pathophysiology behind these effects is multifactorial, relying on
      anatomic and cellular changes. MC is cost effective and potentially cost saving
      in both the United States and Africa. The World Health Organization and Joint
      United Nations Program on HIV/AIDS proposed reaching 80% MC coverage in HIV
      endemic countries, but current rates fall far behind targets. Barriers to scale
      up include supply-side and demand-side challenges. In the United States, neonatal
      MC rates are decreasing, but the American Academy of Pediatrics now recognizes
      the medical benefits of MC and supports insurance coverage. Although MC is a
      globally valuable tool to prevent HIV and other sexually transmitted infections,
      it is underutilized. Further research is needed to address barriers to MC uptake.

PMID- 24111893
TI  - Immunohistochemistry of soft tissue tumours - review with emphasis on 10 markers.
AB  - Immunohistochemistry is an integral component in the proper analysis of soft
      tissue tumours, and a simple panel of six markers is useful in practical triage:
      CD34, desmin, epithelial membrane antigen (EMA), keratin cocktail AE1/AE3, S100
      protein and alpha smooth muscle actin (SMA). These markers frequently assist in
      the differential diagnosis of fibroblastic, myoid, nerve sheath and perineurial
      cell tumours, synovial and epithelioid sarcoma and others. However, they all are
      multispecific, so that one has to be cognizant of their distribution in normal
      and neoplastic tissues. Four additional useful markers for specific tumour types
      are discussed here: CD31 and ERG for vascular endothelial tumours, and KIT and
      DOG1/Ano-1 for gastrointestinal stromal tumours (GISTs). However, hardly any
      marker is totally monospecific for any one type of tumour. Furthermore, variably
      lineage-specific markers do not usually distinguish between benign and malignant
      proliferations, so that this distinction has to be made on histological grounds.
      Immunohistochemical evaluation is most useful, efficient and cost-effective when
      used in the context of careful histological evaluation by an experienced
      pathologist, aware of all diagnostic entities and their histological spectra.
      Additional diagnostic steps that must be considered in difficult cases include
      clinicoradiological correlation and additional sampling of remaining wet tissue,
      if possible. 

PMID- 24111892
TI  - Nuclear receptor coactivators: master regulators of human health and disease.
AB  - Transcriptional coregulators (coactivators and corepressors) have emerged as the
      principal modulators of the functions of nuclear receptors and other
      transcription factors. During the decade since the discovery of steroid receptor
      coactivator-1 (SRC-1), the first authentic coregulator, more than 400
      coregulators have been identified and characterized, and deciphering their
      function has contributed significantly to our understanding of their role in
      human physiology. Deregulated expression of coregulators has been implicated in
      diverse disease states and related pathologies. The advancement of molecular
      technologies has enabled us to better characterize the molecular associations of
      the SRC family of coactivators with other protein complexes in the context of
      gene regulation. These continuing discoveries not only expand our knowledge of
      the roles of coactivators in various human diseases but allow us to discover
      novel coactivator-targeting strategies for therapeutic intervention in these
      diseases. 

PMID- 24111894
TI  - Amphiphilic colloidal surfactants based on electrohydrodynamic co-jetting.
AB  - A novel synthetic route for the preparation of amphiphilic Janus particles based
      on electrohydrodynamic cojetting has been developed. In this approach, selective
      encapsulation of hydrophobic fluorodecyl-polyhedral oligomeric silsesquioxane (F
      POSS) in one compartment and a poly(vinyl alcohol) in the second compartment
      results in colloidal particles with surfactant-like properties including the self
      organization at oil-water and air-water interfaces. Successful localization of
      the respective polymers in different compartments of the same particle is
      confirmed by a combination of fluorescence microscopy, vibrational spectroscopy,
      and zeta-potential measurements. We believe that this straightforward synthetic
      approach may lead to a diverse class of surface-active colloids that will have
      significant relevance ranging from basic scientific studies to immediate
      applications in areas, such as pharmaceutical sciences or cosmetics. 

PMID- 24111895
TI  - Relationship of HIV care engagement to emergency department utilization.
AB  - To determine if HIV primary care engagement (PCE) is associated with Emergency
      Department (ED) utilization, a retrospective cohort study using the South
      Carolina HIV surveillance data from January 1986 to December 2006 linked to the
      hospital discharge data-set was used to assess utilization at statewide EDs
      during January 2007-December 2010. Suboptimal PCE was defined as <2 reports of a
      CD4 + T-cell count or viral load value to surveillance in each calendar year from
      January 2007 to December 2010. Multivariable logistic regression explored
      associations of HIV PCE with ED utilization after accounting for sociodemographic
      characteristics and disease stage. Poisson and negative binominal regression
      examined PCE, sociodemographic characteristics, and disease stage on the
      frequency of ED utilization. Suboptimal PCE was associated with increased odds of
      ED utilization for NIR/NRR (no identified risk/no risk reported; aOR [adjusted
      odds ratio] = 2.25; CI = 1.69-2.99), self-payers (aOR = 1.81; CI = 1.38-2.39),
      and those diagnosed with an AIDS-defining illness (ADI; aOR = 1.51; CI = 1.14
      2.00), who also had the most median ED visits (six). More ED visits were
      associated with young age, female (incidence rate ratio [IRR] = 1.16; CI = 1.06
      1.27), ADI (IRR = 2.17; CI = 1.93-2.45), Medicaid recipients (IRR = 1.34; CI =
      1.21-1.49), indigent/charity recipients (IRR = 1.86; CI = 1.57-2.21), or AIDS > 1
      year (IRR = 1.23; CI = 1.13-1.35). Fewer visits to the ED were associated with
      MSM (males having sex with males IRR = 0.81; CI = 0.72-0.90), NIR/NRR (IRR =
      0.86; CI = 0.78-0.95), self-payers (IRR = 0.56; CI = 0.50-0.62), or Medicare
      recipients (IRR = 0.85; CI = 0.77-0.95). Disease stage and insurance type were
      differentially associated with primary care and ED utilization. There is a need
      to evaluate HIV primary care systems to increase access and develop interventions
      to reduce preventable ED visits. 

PMID- 24111897
TI  - Morphometric evaluation of the fetal rat liver after maternal dexamethasone
      treatment: effect on the maturation of erythroid and megakaryocytic cells.
AB  - BACKGROUND: During pregnancy, glucocorticoids are frequently used to accelerate
      fetal lung maturation in preterm delivery. However, prenatal administration of
      glucocorticoids has been shown to affect organs such as fetal liver, an important
      hematopoietic organ during fetal development. OBJECTIVE: The aim of this study
      was to document the qualitative and quantitative changes in erythroid and
      megakaryocytic cell populations found in fetal livers as well as the hematology
      profile in neonates after maternal glucocorticoid treatment in rats. METHODS:
      Pregnant female Wistar rats were treated with dexamethasone 21-phosphate from
      days 13 to 16 of gestation. On the 17th day of pregnancy, the fetuses were
      collected and their livers processed for light and transmission electron
      microscopy. Glycol methacrylate-embedded sections were stained with PAS to
      determine the erythroblast and megakaryocytic cell frequencies. Fetal liver
      pieces embedded in Spurr resin were analyzed by transmission electron microscopy
      for morphologic changes. A standard hematology profile was evaluated in neonatal
      rats. RESULTS: In the fetuses from treated dams, the total cell number of
      erythroid cells in livers was significantly reduced compared to control fetuses
      (P < .001), but erythroblasts did not present ultrastructural abnormalities. The
      degree of maturation in the megakaryocyte series tended to be increased. In
      neonates, there were elevated numbers of nucleated RBCs (P = .002), along with a
      higher HCT and HGB (P = .02). In addition, the platelet concentration was also
      significantly increased (P < .007). CONCLUSION: These results suggest that
      maternal dexamethasone treatment has quantitative effects on erythroid and
      megakaryocytic cells in fetal liver and the neonatal hematology profile in rats.

PMID- 24111896
TI  - KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary
      arteries.
AB  - BACKGROUND AND PURPOSE: Hypoxia causes vasodilatation of coronary arteries, but
      the underlying mechanisms are poorly understood. We hypothesized that hypoxia
      reduces intracellular Ca(2+) concentration ([Ca(2+)](i)) by opening of K channels
      and release of H2S. EXPERIMENTAL APPROACH: Porcine coronary arteries without
      endothelium were mounted for measurement of isometric tension and [Ca(2+)](i),
      and the expression of voltage-gated K channels K(V)7 channels (encoded by KCNQ
      genes) and large-conductance calcium-activated K channels (K(Ca)1.1) was
      examined. Voltage clamp assessed the role of K(V)7 channels in hypoxia. KEY
      RESULTS: Gradual reduction of oxygen concentration from 95 to 1% dilated the
      precontracted coronary arteries and this was associated with reduced [Ca(2+)](i)
      in PGF(2alpha) (10 MUM)-contracted arteries whereas no fall in [Ca(2+)](i) was
      observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated
      potassium channels and K(Ca)1.1 inhibited hypoxia-induced dilatation in PGF2alpha
      -contracted arteries; this inhibition was more marked in the presence of the
      K(v)7 channel blockers, XE991 and linopirdine, while a K(V)7.1 blocker, failed to
      change hypoxic vasodilatation. XE991 also inhibited H2S- and adenosine-induced
      vasodilatation. PCR revealed the expression of K(V)7.1, K(V)7.4, K(V)7.5 and
      K(Ca)1.1 channels, and K(Ca)1.1, K(V)7.4 and K(V)7.5 were also identified by
      immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more
      marked in hypoxic conditions. CONCLUSION: The K(V)7.4 and K(V)7.5 channels, which
      we identified in the coronary arteries, appear to have a major role in hypoxia
      induced vasodilatation. The voltage clamp results further support the involvement
      of K(V)7 channels in this vasodilatation. Activation of these K(V)7 channels may
      be induced by H2S and adenosine.

PMID- 24111898
TI  - Modeling seizure self-prediction: an e-diary study.
AB  - PURPOSE: A subset of patients with epilepsy successfully self-predicted seizures
      in a paper diary study. We conducted an e-diary study to ensure that prediction
      precedes seizures, and to characterize the prodromal features and time windows
      that underlie self-prediction. METHODS: Subjects 18 or older with localization
      related epilepsy (LRE) and >=3 seizures per month maintained an e-diary,
      reporting a.m./p.m. data daily, including mood, premonitory symptoms, and all
      seizures. Self-prediction was rated by, "How likely are you to experience a
      seizure (time frame)?" Five choices ranged from almost certain (>95% chance) to
      very unlikely. Relative odds of seizure (odds ratio, OR) within time frames was
      examined using Poisson models with log normal random effects to adjust for
      multiple observations. KEY FINDINGS: Nineteen subjects reported 244 eligible
      seizures. OR for prediction choices within 6 h was as high as 9.31 (CI 1.92
      45.23) for "almost certain." Prediction was most robust within 6 h of diary
      entry, and remained significant up to 12 h. For nine best predictors, average
      sensitivity was 50%. Older age contributed to successful self-prediction, and
      self-prediction appeared to be driven by mood and premonitory symptoms. In
      multivariate modeling of seizure occurrence, self-prediction (2.84; CI 1.68
      4.81), favorable change in mood (0.82; CI 0.67-0.99), and number of premonitory
      symptoms (1.11; CI 1.00-1.24) were significant. SIGNIFICANCE: Some persons with
      epilepsy can self-predict seizures. In these individuals, the odds of a seizure
      following a positive prediction are high. Predictions were robust, not
      attributable to recall bias, and were related to self-awareness of mood and
      premonitory features. The 6-h prediction window is suitable for the development
      of preemptive therapy.

PMID- 24111899
TI  - Reference values of skin autofluorescence as an estimation of tissue accumulation
      of advanced glycation end products in a general Slovak population.
AB  - AIMS: For decades, Slovakia has maintained a prominent place in mortality rates
      from cardiovascular diseases among European Union (EU-27) countries.
      Determination of skin autofluorescence serves as an estimate of tissue
      accumulation of advanced glycation end products--substances accumulating in
      tissues and body fluids that play a pathophysiological role in age-related
      diseases and their complications, such as diabetes. METHODS: In 1385 apparently
      healthy Slovakian subjects aged from a few days old to 77 years, skin
      autofluorescence was determined using an advanced glycation end product reader
      and compared with reference data from Dutch Caucasians. The impact of the weekly
      frequency of recreational physical exercise on skin autofluorescence was
      investigated in the adults, and the impact of feeding regimen in the infants.
      RESULTS: With the exception of 10- to 19-year-olds, Slovaks had lower skin
      autofluorescence values in comparison with the Dutch Caucasians. In healthy non
      smokers, physical exercise for > 30 min/day performed >= 3 times/week was
      associated with lower skin autofluorescence levels. In infants, breastfeeding
      (advanced glycation end product-poor diet) was associated with lower skin
      autofluorescence levels in comparison with consumption of infant formulas
      (advanced glycation end product-rich diet). CONCLUSIONS: Reference ranges of skin
      autofluorescence in Slovak Caucasians, detailed for paediatric age groups, are
      provided. Our data show that, in healthy adults, regular physical exercise
      associates with lower skin autofluorescence. Infants fed or weaned from infant
      formulas (advanced glycation end product-rich diet) have higher skin
      autofluorescence than their breast milk-consuming counterparts. It is unclear why
      Slovaks have lower skin autofluorescence compared with a Dutch population with
      lower cardiovascular mortality rates. Reference data on skin autofluorescence
      from diverse populations are needed for the precise clinical interpretation of
      skin autofluorescence measurements.

PMID- 24111900
TI  - European athletes dominate performances in Double Iron ultra-triathlons--a
      retrospective data analysis from 1985 to 2010.
AB  - We investigated the participation and performance trends of ultra-endurance
      triathletes from all nationalities competing in a Double Iron ultra-triathlon
      (7.6-km swim, 360-km cycle and 84.4-km run) from 1985 to 2010. A total of 1854
      athletes participated in 92 Double Iron ultra-triathlons. The majority of the
      winners came from Europe with 72 victories, followed by North America with 17
      victories. The race time for the European ultra-triathletes was 1340 (s=95.3)
      min, decreasing highly significantly (r (2)=0.28; P<0.0001) across the years.
      North American ultra-triathletes finished the races within 1556 (s=124.5) min;
      their race time showed no changes across the years (r (2)=0.045; P=0.07). The
      race time for the Europeans was highly significantly faster compared to the North
      Americans (P<0.0001). Future studies should investigate each country in Europe
      and North America in order to find the country with the largest participation of
      athletes and their best performance.

PMID- 24111901
TI  - Bottom-up construction of POM-based macrostructures: coordination assembled
      paddle-wheel macroclusters and their vesicle-like supramolecular aggregation in
      solution.
AB  - A bottom-up approach to obtain nanoclusters and large, uniform vesicle-like
      structures containing organic functionalized hexamolybdates in solution state
      were developed. Hexamolybdate functionalized carboxylic acid coordinated with two
      copper ions to form paddle-wheel tetrapolyoxometalate clusters with the features
      of macro-ions, which can spontaneously assemble into large, stable blackberry
      type structures in suitable solvents, completing a hierarchical organization from
      small POM molecules to nanoscale complexes and then to supramolecular structures.

PMID- 24111902
TI  - Mutagenesis and computational modeling of human G-protein-coupled receptor Y2 for
      neuropeptide Y and peptide YY.
AB  - Neuropeptide Y and peptide YY receptor type 2 (Y2) is involved in appetite
      regulation and several other physiological processes. We have investigated the
      structure of the human Y2 receptor. Computational modeling of receptor-agonist
      interactions was used as a guide to design a series of receptor mutants, followed
      by binding assays using full-length and truncated peptide agonists and the Y2
      specific antagonist BIIE0246. Our model suggested a hydrogen bond network among
      highly conserved residues Thr2.61, Gln3.32, and His7.39, which could play roles
      in ligand binding and/or receptor structure. In addition, the C-terminus of the
      peptide could make contact with residues Tyr5.38 and Leu6.51. Mutagenesis of all
      these positions, followed by binding assays, provides experimental support for
      our computational model: most of the mutants for the residues forming the
      proposed hydrogen bond network displayed reduced peptide agonist affinities as
      well as reduced hPYY3-36 potency in a functional assay. The Ala and Leu mutants
      of Gln3.32 and His7.39 disrupted membrane expression of the receptor. Combined
      with the modeling, the experimental results support roles for these hydrogen bond
      network residues in peptide binding as well as receptor architecture. The reduced
      agonist affinity for mutants of Tyr5.38 and Leu6.51 supports their role in a
      binding pocket surrounding the invariant tyrosine at position 36 of the peptide
      ligands. The results for antagonist BIIE0246 suggest several differences in
      interactions compared to those of the peptides. Our results lead to a new
      structural model for NPY family receptors and peptide binding. 

PMID- 24111903
TI  - The epidemiology and burden of COPD in Latin America and the Caribbean:
      systematic review and meta-analysis.
AB  - Abstract Background: In the developing world, COPD continues to be an under
      studied, diagnosed and treated disorder. In the present study, we analyzed the
      prevalence, mortality and resource utilization of COPD in Latin America and the
      Caribbean (LAC) in order to guide future research and public policies. METHODS: A
      systematic review and meta-analysis was performed following MOOSE and PRISMA
      guidance. We searched CENTRAL, MEDLINE, EMBASE, LILACS, countries' Ministries of
      Health, proceedings, and doctoral theses from January 1990 to October 2012. We
      included studies with a validated definition of COPD that assessed the incidence,
      prevalence, use of health care resources or costs since 1985. Using EROS, a web
      based software, pairs of reviewers independently selected, performed quality
      assessment (using a STROBE-based checklist) and extracted the study data.
      Discrepancies were resolved by consensus. Arcsine transformations and random
      effects model were used for proportion meta-analyses. RESULTS: 26 articles met
      entry criteria. The pooled COPD prevalence defined by GOLD criteria (11 cities, 6
      countries) was 13.4% (95%CI, 10.1-17.1). Most patients suffer mild or moderate
      COPD and were undertreated according to international guidelines. The prevalence
      increased by age and was 1.75 times higher in men than women. 35 of every 1,000
      hospitalizations were due to COPD, most of high economic cost, and the COPD in
      hospital mortality ranged from 6.7% to 29.5%. CONCLUSIONS: COPD burden in LAC is
      high, especially for men and older persons; however few persons had severe
      disease. COPD patients often received inappropriate treatment and had high
      exacerbation and hospitalization rates leading to high economic costs.

PMID- 24111904
TI  - The bovine patella as a model of early osteoarthritis.
AB  - The bovine patella model has been used extensively for studying important
      structure-function aspects of articular cartilage, including its degeneration.
      However, the degeneration seen in this model has, to our knowledge, never been
      adequately compared with human osteoarthritis (OA). In this study, bovine
      patellae displaying normal to severely degenerate states were compared with human
      tissue displaying intact cartilage to severe OA. Comparisons of normal and OA
      features were made with histological scoring, morphometric measurements, and
      qualitative observations. Differential interference contrast microscopy was used
      to image early OA changes in the articular cartilage matrix and to investigate
      whether this method provided comparable quality of visualisation of key
      structural features with standard histology. The intact bovine cartilage was
      found to be similar to healthy human cartilage and the degenerate bovine
      cartilage resembled the human OA tissues with regard to structural disruption,
      cellularity changes, and staining loss. The extent of degeneration in the bovine
      tissues matched the mild to moderate range of human OA tissues; however, no
      bovine samples exhibited late-stage OA. Additionally, in both bovine and human
      tissues, cartilage degeneration was accompanied by calcified cartilage
      thickening, tidemark duplication, and the advancement of the cement line by
      protrusions of bony spicules into the calcified cartilage. This comparison of
      degeneration in the bovine and human tissues suggests a common pathway for the
      progression of OA and thus the bovine patella is proposed to be an appropriate
      model for investigating the structural changes associated with early OA. 

PMID- 24111905
TI  - Cardiac complications and diabetes in thalassaemia major: a large historical
      multicentre study.
AB  - The relationship between diabetes mellitus (DM) and cardiac complications has
      never been systematically studied in thalassaemia major (TM). We evaluated a
      large retrospective historical cohort of TM to determine whether DM is associated
      with a higher risk of heart complications. We compared 86 TM patients affected by
      DM with 709 TM patients without DM consecutively included in the Myocardial Iron
      Overload in Thalassaemia database where clinical/instrumental data are recorded
      from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the
      cardiac events considered were developed after the DM diagnosis. In DM patients
      versus non-DM patients we found a significantly higher frequency of cardiac
      complications (46.5% vs. 16.9%, P < 0.0001), heart failure (HF) (30.2% vs. 11.7%,
      P < 0.0001), hyperkinetic arrhythmias (18.6% vs. 5.5%, P < 0.0001) and myocardial
      fibrosis assessed by late gadolinium enhancement (29.9% vs. 18.4%, P = 0.008). TM
      patients with DM had a significantly higher risk of cardiac complications [odds
      ratio (OR) 2.84, P < 0.0001], HF (OR 2.32, P = 0.003), hyperkinetic arrhythmias
      (OR 2.21, P = 0.023) and myocardial fibrosis (OR 1.91, P = 0.021), also adjusting
      for the absence of myocardial iron overload assessed by T2* CMR and for the
      covariates (age and/or endocrine co-morbidity). In conclusion, DM significantly
      increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and
      myocardial fibrosis in TM patients.

PMID- 24111906
TI  - Recent advances in the synthesis of new antimycobacterial agents based on the 1H
      1,2,3-triazoles.
AB  - The 1H-1,2,3-triazoles have been studied for many years as an important class of
      heterocyclic compounds and still attracting considerable attention due to their
      several application such as, organocatalyst, ionic liquid and broad range of
      biological activities, including several neglected diseases as tuberculosis. This
      review emphasizes the recent advances of these triazoles and their perspective in
      the development of new bioactive chemical entities against tuberculosis. 

PMID- 24111907
TI  - An update on the chemistry and medicinal chemistry of novel antimycobacterial
      compounds.
AB  - Tuberculosis (TB) is a serious public health issue, particularly in
      underdeveloped and developing countries. Furthermore the first-line anti-TB
      treatments were established over 40 years ago, multidrug-resistant Mycobacterium
      tuberculosis strains have been developed and the risk of coinfection with AIDS
      virus has highlighted this disease as a global emergency. The urgent need for
      more effective treatments against multidrug-resistant strains compatible with
      anti-AIDS drugs has prompted industries, governments and non-governmental
      agencies to pursue new drugs. In this study, we update the portfolio listed at
      Stop TB Partnership, present the biological activities as well as structure
      activity relationship for these drugs and thoroughly discuss the synthetic
      methodologies used to produce these drugs. 

PMID- 24111908
TI  - Fluorinated compounds against Mycobacterium tuberculosis.
AB  - Tuberculosis is a severe infectious disease currently being treated with drugs
      that were developed more than 40 years ago. In recent years, the emergence of
      resistant Mycobacterium tuberculosis strains, as well as co-infection with the
      AIDS virus, has caused global concern about the evolution of the disease. Thus,
      the search for new drugs has become a necessity and a great challenge. Fluorine
      is a strategic element that is very useful in medicinal chemistry for its great
      influence on the biological activity of substances. This review highlights the
      importance of fluorinated molecules that are currently in clinical use or pre
      clinical phases of development. Further, some substances in the prototype
      development stage are cited, which potentially represent future alternatives for
      the treatment of tuberculosis. 

PMID- 24111909
TI  - Targeting the histidine pathway in Mycobacterium tuberculosis.
AB  - Worldwide, tuberculosis is the leading cause of morbidity and mortality due to a
      single bacterial pathogen, Mycobacterium tuberculosis (Mtb). The increasing
      prevalence of this disease, the emergence of multi-, extensively, and totally
      drug-resistant strains, complicated by co-infection with the human
      immunodeficiency virus, and the length of tuberculosis chemotherapy have led to
      an urgent and continued need for the development of new and more effective
      antitubercular drugs. Within this context, the L-histidine biosynthetic pathway,
      which converts 5-phosphoribosyl 1-pyrophosphate to L-histidine in ten enzymatic
      steps, has been reported as a promising target of antimicrobial agents. This
      pathway is found in bacteria, archaebacteria, lower eukaryotes, and plants but is
      absent in mammals, making these enzymes highly attractive targets for the drug
      design of new antimycobacterial compounds with selective toxicity. Moreover, the
      biosynthesis of L-histidine has been described as essential for Mtb growth in
      vitro. Accordingly, a comprehensive overview of Mycobacterium tuberculosis
      histidine pathway enzymes as attractive targets for the development of new
      antimycobacterial agents is provided, mainly summarizing the previously reported
      inhibition data for Mtb or orthologous proteins. 

PMID- 24111910
TI  - Editorial: new developments in the search for agents to treat tuberculosis.

PMID- 24111911
TI  - Gammaherpesviruses and lymphoproliferative disorders.
AB  - Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV), formally
      designated human herpesvirus 4 (HHV-4) and 8 (HHV-8), respectively, are viruses
      that can cause a variety of cancers in humans. EBV is found in non-Hodgkin and
      Hodgkin lymphomas, as well as in lymphoproliferative disorders, which occur more
      commonly but not exclusively in individuals with immunodeficiency. EBV also
      causes nonlymphoid malignancies such as nasopharyngeal carcinoma. KSHV causes
      primary effusion lymphomas, multicentric Castleman's disease, and Kaposi's
      sarcoma. The frequency of lymphoid malignancies related to infection by one of
      these two herpesviruses is greatly increased in individuals with
      immunodeficiency, whether primary or acquired, for example, as a consequence of
      HIV infection and AIDS or in the case of therapeutic immunosuppression for organ
      transplantation. Our current understanding indicates that EBV and KSHV contribute
      to lymphomagenesis by affecting genomic stability and by subverting the cellular
      molecular signaling machinery and metabolism to avoid immune surveillance and
      enhance tumor cell growth and survival. Understanding the viral associations in
      specific lymphoproliferative disorders and the molecular mechanisms of viral
      oncogenesis will lead to better prevention, diagnosis, and treatment strategies
      for these diseases. 

PMID- 24111912
TI  - IgG4-related disease.
AB  - Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated
      condition that can affect almost any organ and is now being recognized with
      increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate
      composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and
      mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous
      fibroinflammatory conditions that had previously been thought to be confined to
      single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely
      cause progressive fibrosis and organ damage. IgG4 antibodies are generally
      regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed
      in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab
      induced B cell depletion in IgG4-RD leads to rapid clinical and histological
      improvement accompanied by swift declines in serum IgG4 concentrations. Although
      IgG autoantibodies against various exocrine gland antigens have been described in
      IgG4-RD, whether they are members of the IgG4 subclass is unknown. The
      contribution of autoantibodies to IgG4-RD remains unclear. 

PMID- 24111914
TI  - Vibrational energy flow between modes by dynamic mode coupling in THIATS J
      aggregates.
AB  - We performed ultrafast pump-probe spectroscopy of J-aggregates of 3,3'
      disulfopropyl-5,5'-dichloro-9-ethyl thiacarbocyanine triethylammonium (THIATS),
      one of the most typical cyanine dyes, and detected excited molecular vibrations,
      using a sub-10 fs pulse laser. The time-resolved two-dimensional difference
      absorption (DeltaA) spectra are observed between -314 and 1267 fs. By performing
      the Fourier transform and spectrogram analysis, vibrational modes in THIATS are
      observed at 285, 485, 555, 824, and 1633 cm(-1) and there was a modulation of the
      vibrational frequencies around 1633 cm(-1) which depend on the delay time,
      respectively. By the analysis of the modulation, energy flow is found to take
      place from other modes to the 1633 cm(-1) mode through the low frequency mode
      with ~50 cm(-1). Also, by fitting the real-time traces of DeltaA with the sum of
      two exponential functions and a constant term, the average lifetimes of three
      electronically excited states were found to be tau1 = 52 +/- 5 fs and tau2 = 540
      +/- 78 fs. By performing single-exponential fitting around the stationary
      absorption peak at 1.990 eV, in the negative time range, the electronic dephasing
      time, T2(ele), is determined to be 18.30 fs. 

PMID- 24111913
TI  - Systemic control of brown fat thermogenesis: integration of peripheral and
      central signals.
AB  - Brown adipose tissue (BAT) is of great scientific interest as a potential target
      to treat obesity. The development of novel strategies to quantify brown fat
      thermogenesis in adult humans now enables minimally invasive assessment of novel
      pharmacotherapeutics. Input from the central nervous system via sympathetic
      efferents is widely regarded as the key controller of BAT-mediated thermogenesis
      in response to changes in body temperature or nutrient availability. More
      recently, however, it has become clear that locally secreted signals and
      endocrine factors originating from multiple organs can control the recruitment of
      brown adipocytes and, more importantly, induce thermogenesis in brown fat. Thus,
      they provide an attractive strategy to fine-tune brown fat thermogenesis
      independent of classical temperature sensing. Here, we summarize recent findings
      on bone morphogenetic protein signaling as an example of secreted factors in the
      regulation of brown adipocyte formation and systemic control of energy
      metabolism. We further highlight endocrine communication routes between the
      different types of brown adipocytes and other organs that contribute to
      regulation of thermogenesis. Thus, emerging evidence suggests that the classical
      mechanisms of central temperature sensing and sympathetic nervous system-driven
      thermogenesis are complemented by local and endocrine signals to determine
      systemic energy homeostasis. 

PMID- 24111915
TI  - Three-dimensional nanomechanical mapping of amorphous and crystalline phase
      transitions in phase-change materials.
AB  - The nanostructure of micrometer-sized domains (bits) in phase-change materials
      (PCM) that undergo switching between amorphous and crystalline phases plays a key
      role in the performance of optical PCM-based memories. Here, we explore the
      dynamics of such phase transitions by mapping PCM nanostructures in three
      dimensions with nanoscale resolution by combining precision Ar ion beam cross
      sectional polishing and nanomechanical ultrasonic force microscopy (UFM) mapping.
      Surface and bulk phase changes of laser written submicrometer to micrometer sized
      amorphous-to-crystalline (SET) and crystalline-to-amorphous (RESET) bits in
      chalcogenide Ge2Sb2Te5 PCM are observed with 10-20 nm lateral and 4 nm depth
      resolution. UFM mapping shows that the Young's moduli of crystalline SET bits
      exceed the moduli of amorphous areas by 11 +/- 2%, with crystalline content
      extending from a few nanometers to 50 nm in depth depending on the energy of the
      switching pulses. The RESET bits written with 50 ps pulses reveal shallower depth
      penetration and show 30-50 nm lateral and few nanometer vertical wavelike
      topography that is anticorrelated with the elastic modulus distribution. Reverse
      switching of amorphous RESET bits results in the full recovery of subsurface
      nanomechanical properties accompanied with only partial topography recovery,
      resulting in surface corrugations attributed to quenching. This precision
      sectioning and nanomechanical mapping approach could be applicable to a wide
      range of amorphous, nanocrystalline, and glass-forming materials for 3D
      nanomechanical mapping of amorphous-crystalline transitions. 

PMID- 24111916
TI  - Periocular cutaneous oncocytoma with signs of disrupted oxygen metabolism.
AB  - Oncocytomas are benign tumors most often occurring in salivary or lacrimal glands
      and thyroid tissue. As cutaneous oncocytoma is exceptionally rare, this tumor is
      uncommonly encountered by dermatopathologists. Herein, we illustrate the case of
      an 80-year-old man who presented with a slowly growing papule of the lower
      eyelid. Histopathologically, the adenomatous tumor was composed of large
      monomorphic cells with eosinophilic granular cytoplasm. Electron microscopy
      revealed abundant, enlarged and abnormally shaped mitochondria. These findings
      were consistent with an oncocytoma of the skin. The presented case is unique in
      that the thorough work-up of the tumor tissue revealed not only hyperplastic
      mitochondria, representing the ultrastructural correlate of the observed granular
      cytoplasm, but additionally disclosed functional consequences with elevated
      levels of reactive oxygen specimen (ROS) within the tumor. Disrupted oxygen
      metabolism may result from cellular aging processes and may putatively represent
      the underlying pathogenesis of oncocytoma. 

PMID- 24111917
TI  - A model-based 'varimax' sampling strategy for a heterogeneous population.
AB  - BACKGROUND AND AIMS: Sampling strategies are planned to enhance the homogeneity
      of a sample, hence to minimize confounding errors. A sampling strategy was
      developed to minimize the variation within population groups. Karachi, the
      largest urban agglomeration in Pakistan, was used as a model population. SUBJECTS
      AND METHODS: Blood groups ABO and Rh factor were determined for 3000 unrelated
      individuals selected through simple random sampling. Among them five population
      groups, namely Balochi, Muhajir, Pathan, Punjabi and Sindhi, based on paternal
      ethnicity were identified. An index was designed to measure the proportion of
      admixture at parental and grandparental levels. Population models based on index
      score were proposed. For validation, 175 individuals selected through stratified
      random sampling were genotyped for the three STR loci CSF1PO, TPOX and TH01.
      RESULTS: ANOVA showed significant differences across the population groups for
      blood groups and STR loci distribution. Gene diversity was higher across the sub
      population model than in the agglomerated population. At parental level gene
      diversities are significantly higher across No admixture models than Admixture
      models. At grandparental level the difference was not significant. CONCLUSION: A
      sub-population model with no admixture at parental level was justified for
      sampling the heterogeneous population of Karachi.

PMID- 24111918
TI  - Long-term efficacy and safety of tacrolimus ointment in the treatment of
      vitiligo.

PMID- 24111920
TI  - The C-terminus of Wheat streak mosaic virus coat protein is involved in
      differential infection of wheat and maize through host-specific long-distance
      transport.
AB  - Viral determinants and mechanisms involved in extension of host range of monocot
      infecting viruses are poorly understood. Viral coat proteins (CP) serve many
      functions in almost every aspect of the virus life cycle. The role of the C
      terminal region of Wheat streak mosaic virus (WSMV) CP in virus biology was
      examined by mutating six negatively charged aspartic acid residues at positions
      216, 289, 290, 326, 333, and 334. All of these amino acid residues are
      dispensable for virion assembly, and aspartic acid residues at positions 216,
      333, and 334 are expendable for normal infection of wheat and maize. However,
      mutants D289N, D289A, D290A, DD289/290NA, and D326A exhibited slow cell-to-cell
      movement in wheat, which resulted in delayed onset of systemic infection,
      followed by a rapid recovery of genomic RNA accumulation and symptom development.
      Mutants D289N, D289A, and D326A inefficiently infected maize, eliciting milder
      symptoms, while D290A and DD289/290NA failed to infect systemically, suggesting
      that the C-terminus of CP is involved in differential infection of wheat and
      maize. Mutation of aspartic acid residues at amino acid positions 289, 290, and
      326 severely debilitated virus ingress into the vascular system of maize but not
      wheat, suggesting that these amino acids facilitate expansion of WSMV host range
      through host-specific long-distance transport. 

PMID- 24111921
TI  - Effects of pill burden on discontinuation of the initial HAART regimen in
      minority female patients prescribed 1 pill/day versus any other pill burden.
AB  - Highly active antiretroviral therapy (HAART) is a mainstay of treatment for
      patients with Human Immunodeficiency Virus (HIV). Since second line HAART
      therapies can be costlier and less effective, it is essential to understand the
      duration of initial HAART therapies. The overall aim of this study was to
      estimate the effects of daily pill burden on the time to discontinuation of the
      initial HAART regimen. Patients were initially identified through the clinic's
      CAREWARE database. A chart review was conducted for data collection, where only
      adult, female, HIV-positive patients initiating therapy at the study clinic
      between 1 January 2001 and 31 December 2011 were included. All study subjects
      were followed up from the initiation of HAART to treatment discontinuation. A
      Kaplan-Meier curve was generated to describe time to discontinuation by regimens,
      and a Cox proportional hazards model was developed to assess the impact of
      different regimen and patient demographic characteristics on the hazard of
      discontinuation of the initial regimen. A total of 498 charts were initially
      reviewed. After assessment of these patients for inclusion criteria, a cohort of
      115 adult female patients who initiated HAART at the study clinic was included.
      Patients treated with 1 pill/day regimen had a significantly longer time to
      discontinuation than regimens of >1 pills/day (mean duration of initial therapy
      was 1062.56 days vs. 631.70 days, respectively, p = 0.003). Compared to 1
      pill/day regimens, >1 pills/day regimens were associated with a higher hazard of
      discontinuation (hazard ratio (HR) =3.44 with 95% confidence interval (CI) =
      1.25, 9.48). A higher viral load and patients without insurance were also found
      to be significantly associated with increased hazards of discontinuation.
      Overall, female HIV patients initiating therapy with the 1 pill/day HAART regimen
      were less likely to discontinue their treatment compared to patients initiating
      with >1 pills/day HAART regimen. 

PMID- 24111919
TI  - Corticosterone administration up-regulated expression of norepinephrine
      transporter and dopamine beta-hydroxylase in rat locus coeruleus and its terminal
      regions.
AB  - Stress has been reported to activate the locus coeruleus (LC)-noradrenergic
      system. In this study, corticosterone (CORT) was orally administrated to rats for
      21 days to mimic stress status. In situ hybridization measurements showed that
      CORT ingestion significantly increased mRNA levels of norepinephrine transporter
      (NET) and dopamine beta-hydroxylase (DBH) in the LC region. Immunofluorescence
      staining and western blotting revealed that CORT treatment also increased protein
      levels of NET and DBH in the LC, as well as NET protein levels in the
      hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase
      in DBH protein levels only appeared in the hippocampus and the amygdala. Elevated
      NET and DBH expression in most of these areas (except for NET protein levels in
      the LC) was abolished by simultaneous treatment with combination of
      corticosteroid receptor antagonist mifepristone and spironolactone (s.c. for 21
      days). Also, treatment with mifepristone alone prevented CORT-induced increases
      of NET expression and DBH protein levels in the LC. In addition, behavioral tasks
      showed that CORT ingestion facilitated escape in avoidance trials using an
      elevated T-maze, but interestingly, there was no significant effect on the escape
      trial. Corticosteroid receptor antagonists failed to counteract this response in
      CORT-treated rats. In the open-field task, CORT treatment resulted in less
      activity in a defined central zone compared to controls and corticosteroid
      receptor antagonist treatment alleviated this increase. In conclusion, this study
      demonstrates that chronic exposure to CORT results in a phenotype that mimics
      stress-induced alteration of noradrenergic phenotypes, but the effects on
      behavior are task dependent. As the sucrose consumption test strongly suggests
      CORT ingestion-induced depression-like behavior, further elucidation of
      underlying mechanisms may improve our understanding of the correlation between
      stress and the development of depression.

PMID- 24111922
TI  - Copper(I) nitrosyls from reaction of copper(II) thiolates with S-nitrosothiols:
      mechanism of NO release from RSNOs at Cu.
AB  - S-nitrosothiols (RSNOs) serve as ready sources of biological nitric oxide
      activity, especially in conjunction with copper centers. We report a novel
      pathway for the generation of NO within the coordination sphere of copper model
      complexes from reaction of copper(II) thiolates with S-nitrosothiols. Reaction of
      tris(pyrazolyl)borate copper(II) thiolates (iPr2)TpCu-SR (R = C6F5 or CPh3) with
      (t)BuSNO leads to formation of (iPr2)TpCu(NO) and the unsymmetrical disulfide RS
      S(t)Bu. Quantum mechanical investigations with B3LYP-D3/6-311G(d) suggest
      formation of a kappa(1)-N-RSNO adduct (iPr2)TpCu(SR)(R'SNO) that precedes release
      of RSSR' to deliver (iPr2)TpCu(NO). This process is reversible; reaction of
      (iPr2)TpCu(NO) (but not (iPr2)TpCu(NCMe)) with C6F5S-SC6F5 forms (iPr2)TpCu
      SC6F5. Coupled with the facile, reversible reaction between (iPr2)TpCu(NO) and
      C6F5SNO to give (iPr2)TpCu-SC6F5 and 2 equiv NO, we outline a new, detailed
      catalytic cycle for NO generation from RSNOs at Cu. 

PMID- 24111924
TI  - Effect of thermal processing and canning on cadmium and lead levels in California
      market squid: the role of metallothioneins.
AB  - The effects of two common seafood preparation practices (roasting and industrial
      canning) on the heavy metal content--cadmium (Cd) and lead (Pb)--of various
      tissues of California market squid were studied. Emphasis was placed on the role
      of metallothioneins (MT) in Cd and Pb behaviour during processing. Cd and Pb
      analysis was conducted by a Zeeman GTA-AAS atomic absorption spectrometry system;
      MT analysis was performed by a mercury saturation assay. Results showed that Cd
      levels in the mantle and whole squid were considerably affected by both
      processing practices, reaching a 240% increase in mantle and a 40% increase in
      whole squid. Interestingly, Cd behaviour was associated with MT changes during
      squid processing. On the other hand, Pb content was not affected from either
      processing or associated with MT content in the raw or processed squid.
      Therefore, processing operations may affect Cd and Pb content differently due to
      the specific metal bioaccumulation and chemical features of each heavy metal
      type.

PMID- 24111923
TI  - GPBA: a GPCR for bile acids and an emerging therapeutic target for disorders of
      digestion and sensation.
AB  - Bile acids (BAs) are digestive secretions that are necessary for the
      emulsification and absorption of dietary fats. Given the episodic nature of BA
      secretion and intestinal re-absorption, the circulating and tissue levels of BAs,
      like those of the gut hormones, fluctuate in fasting and fed states, and BA
      levels and forms are markedly affected by disease. BAs exert widespread hormonal
      like effects by activating receptors in the nucleus and at the plasma membrane.
      The nuclear steroid receptors mediate the genomic actions of BAs on BA, glucose
      and lipid homeostasis. GPBA (TGR5) is a G-protein coupled plasma membrane
      receptor for BAs that mediates many of the rapid, non-genomic actions of BAs.
      GPBA has been implicated in the control of glucose homeostasis, inflammation and
      liver functions. Recent observations have revealed an unexpected role for GPBA in
      the nervous system. GPBA is expressed by enteric neurons and enterochromaffin
      cells that control peristalsis, and GPBA mediates the prokinetic actions of BAs
      in the colon that have been known for millennia. GPBA is also present on primary
      spinal afferent and spinal neurons that are necessary for sensory transduction.
      BA-induced activation of GPBA in the sensory nervous system promotes scratching
      behaviours and analgesia, which may contribute to the pruritus and painless
      jaundice that are observed in some patients with chronic cholestatic disease,
      where circulating BA concentrations are markedly increased. Thus, GPBA has
      emerged as an intriguing target for diverse metabolic, inflammatory, digestive
      and sensory disorders, where agonists and antagonists may be of value.

PMID- 24111925
TI  - Beyond bevacizumab: investigating new angiogenesis inhibitors in ovarian cancer.
AB  - INTRODUCTION: Ovarian cancer is the most lethal gynecological cancer, mainly
      because of the advanced stage of the disease at diagnosis, with recent research
      investigating novel targets and agents into the clinical practice, with the aim
      to improve prognosis and quality of life. Angiogenesis is a significant target
      for ovarian cancer therapy. AREAS COVERED: Areas covered in this review include
      the most common molecular pathways of angiogenesis, which have provided novel
      targets for tailored therapy in ovarian cancer patients. These therapeutic
      strategies comprise monoclonal antibodies and tyrosine kinase inhibitors. These
      drugs have as molecular targets such as vascular endothelial growth factor
      (VEGF), VEGF receptor, platelet-derived growth factor, fibroblast growth factor,
      angiopoietin and Ephrin type-A receptor 2. EXPERT OPINION: The expansion in
      understanding the molecular biology that characterizes cancer cells has led to
      the rapid development of new agents to target important pathways, but the
      heterogeneity of ovarian cancer biology indicates that there is no predominant
      defect. This review attempts to discuss progress till date in tackling a more
      general target applicable to ovarian cancer angiogenesis.

PMID- 24111927
TI  - Retinopathy, nephropathy, peripheral neuropathy and geriatric scale scores in
      elderly people with Type 2 diabetes.
AB  - AIMS: To analyse the relationships between retinopathy, nephropathy, peripheral
      neuropathy and geriatric scale scores in elderly people with Type 2 diabetes.
      METHODS: GERODIAB is the first French multi-centre, prospective, observational
      study designed to assess the influence of glycaemic control on mortality and
      morbidity through a 5-year follow-up study in people with Type 2 diabetes aged 70
      years and older. In this report the relationships at baseline between
      retinopathy, nephropathy and peripheral neuropathy, and five geriatric scale
      scores in 987 people, using bivariate and multivariate analyses are analysed.
      RESULTS: Retinopathy (26%) was significantly associated with impaired scores on
      the Mini Geriatric Depression Scale, the Mini Nutritional Assessment and the
      Instrumental Activities of Daily Living scale. Logistic regression showed that
      the duration of diabetes, BMI, Mini Geriatric Depression Scale, hypoglycaemia and
      HbA1c were associated with retinopathy (concordance 69.1%; P < 0.001).
      Nephropathy (47.4%, including 34.8% with Modification of Diet in Renal Disease <
      60 ml/min) was significantly associated with impaired Activities of Daily Living
      and Instrumental Activities of Daily Living scale scores. Using the logistic
      model, the most significant factors were age, duration of diabetes,
      triglycerides, HDL cholesterol, hypoglycaemia, hypertension and BMI (concordance
      66.3%; P < 0.001). Peripheral neuropathy (28.2%) was associated with impaired
      scores on the Mini Mental State Examination, Activities of Daily Living,
      Instrumental Activities of Daily Living and Mini Geriatric Depression Scales. In
      the logistic model, diastolic blood pressure, duration of diabetes and the
      Instrumental Activities of Daily Living, Mini Geriatric Depression Scale and Mini
      Mental State Examination scales were included (concordance 69.8%; P < 0.001).
      CONCLUSION: In this specific sample, classical microvascular complications of
      diabetes were found to be associated with impaired geriatric scale scores. This
      highlights the benefits of systematic assessment in elderly people with Type 2
      diabetes.

PMID- 24111928
TI  - Mercury trends in predatory fish in Great Slave Lake: the influence of
      temperature and other climate drivers.
AB  - Here we report on trends in mercury (Hg) concentrations in lake trout (Salvelinus
      namaycush), burbot (Lota lota), and northern pike (Esox lucius) from Great Slave
      Lake, located in the Mackenzie River Basin (MRB) and investigate how climate
      factors may be influencing these trends. Hg concentrations in lake trout and
      burbot increased significantly over the early 1990s to 2012 in the two major
      regions of the lake; no trend was evident for northern pike over 1999-2012.
      Temporal variations in Hg concentrations in lake trout and burbot were similar
      with respect to timing of peaks and troughs. Inclusion of climate variables based
      on annual means, particularly temperature, improved explanatory power for
      variations in Hg over analyses based only on year and fish length; unexpectedly,
      the temperature coefficient was negative. Climate analyses based on growing
      season means (defined as May-September) had less explanatory power suggesting
      that trends were more strongly associated with colder months within the year.
      Inclusion of the Pacific/North American index improved explanatory power for the
      lake trout model suggesting that trends may have been affected by air circulation
      patterns. Overall, while our study confirmed previously reported trends of Hg
      increase in burbot in the MRB, we found no evidence that these trends were
      directly driven by increasing temperatures and productivity. 

PMID- 24111929
TI  - Exercise endurance in chronic obstructive pulmonary disease patients at an
      altitude of 2640 meters breathing air and oxygen (FIO2 28% and 35%): a randomized
      crossover trial.
AB  - BACKGROUND: At Bogota's altitude (2640 m), the lower barometric pressure (560
      mmHg) causes severe hypoxemia in COPD patients, limiting their exercise capacity.
      The aim was to compare the effects of breathing oxygen on exercise tolerance.
      METHODS: In a blind, crossover clinical study, 29 COPD patients (FEV1 42.9 +/-
      11.9%) breathed room air (RA) or oxygen (FIO2 28% and 35%) during three treadmill
      exercise tests at 70% of their maximal capacity in a randomized order. Endurance
      time (ET), inspiratory capacity (IC), arterial blood gases and lactate were
      compared. RESULTS: At the end of the exercise breathing RA, the ET was 9.7 +/-
      4.2 min, the PaO2 46.5 +/- 8.2 mmHg, the lactate increased and the IC decreased.
      The oxygen significantly increased the ET (p < 0.001), without differences
      between 28% (16.4 +/- 6.8 min) and 35% (17.6 +/- 7.0 min) (p = 0.22). Breathing
      oxygen, there was an increase in the PaO2 and SaO2, higher with FIO2 35%, and a
      decrease in the lactate level. At "isotime" (ET at RA), with oxygen, the SpO2,
      the oxygen pulse and the IC were higher and the heart rate lower than breathing
      RA (p < 0.05). CONCLUSION: Oxygen administration for COPD patients in Bogota
      significantly increased ET by decreased respiratory load, improved cardiovascular
      performance and oxygen transport. The higher increases of the PaO2 and SaO2 with
      35% FIO2 did not represent a significant advantage in the ET. This finding has
      important logistic and economic implications for oxygen use in rehabilitation
      programs of COPD patients at the altitude of Bogota and similar altitudes.

PMID- 24111930
TI  - Motivating student learning using a formative assessment journey.
AB  - Providing formative assessment opportunities has been recognised as a significant
      benefit to student learning. The outcome of any formative assessment should be
      one that ultimately helps improve student learning through familiarising students
      with the levels of learning required, informing them about gaps in their learning
      and providing feedback to guide the direction of learning. This article provides
      an example of how formative assessments can be developed into a formative
      assessment journey where a number of different assessments can be offered to
      students during the course of a module of teaching, thus utilising a spaced
      education approach. As well as incorporating the specific drivers of formative
      assessment, we demonstrate how approaches deemed to be stimulating, interactive
      and entertaining with the aim of maximising enthusiasm and engagement can be
      incorporated. We provide an example of a mixed approach to evaluating elements of
      the assessment journey that focuses student reaction, appraisal of qualitative
      and quantitative feedback from student questionnaires, focus group analysis and
      teacher observations. Whilst it is not possible to determine a quantifiable
      effect of the assessment journey on student learning, usage data and student
      feedback shows that formative assessment can achieve high engagement and positive
      response to different assessments. Those assessments incorporating an active
      learning element and a quiz-based approach appear to be particularly popular. A
      spaced-education format encourages a building block approach to learning that is
      continuous in nature rather than focussed on an intense period of study prior to
      summative examinations. 

PMID- 24111931
TI  - Relatives of patients with depression: experiences of everyday life.
AB  - The aim of this study was to describe experiences of everyday life as a relative
      of a person diagnosed with depression. A qualitative and descriptive design with
      a phenomenographic approach was chosen, and individual interviews with 24
      relatives were carried out. Approval was given by the Regional Committee for
      Medical and Health Research Ethics, Norway (South East) ref 2010/126. The
      findings show the main category 'Living on the other person's terms', which may
      be expressed in terms of consideration for the next of kin, thus presenting a
      challenge and a need to be balanced against taking care of oneself. In addition,
      three descriptive categories emerged: 'Ambivalent relationship', 'Adjusting daily
      life' and 'Managing the situation'. In conclusion, the relatives of persons with
      depression may be in danger of developing their own health problems and in need
      for attention from health personnel. 

PMID- 24111926
TI  - Health risks of space exploration: targeted and nontargeted oxidative injury by
      high-charge and high-energy particles.
AB  - SIGNIFICANCE: During deep space travel, astronauts are often exposed to high
      atomic number (Z) and high-energy (E) (high charge and high energy [HZE])
      particles. On interaction with cells, these particles cause severe oxidative
      injury and result in unique biological responses. When cell populations are
      exposed to low fluences of HZE particles, a significant fraction of the cells are
      not traversed by a primary radiation track, and yet, oxidative stress induced in
      the targeted cells may spread to nearby bystander cells. The long-term effects
      are more complex because the oxidative effects persist in progeny of the targeted
      and affected bystander cells, which promote genomic instability and may increase
      the risk of age-related cancer and degenerative diseases. RECENT ADVANCES:
      Greater understanding of the spatial and temporal features of reactive oxygen
      species bursts along the tracks of HZE particles, and the availability of
      facilities that can simulate exposure to space radiations have supported the
      characterization of oxidative stress from targeted and nontargeted effects.
      CRITICAL ISSUES: The significance of secondary radiations generated from the
      interaction of the primary HZE particles with biological material and the
      mitigating effects of antioxidants on various cellular injuries are central to
      understanding nontargeted effects and alleviating tissue injury. FUTURE
      DIRECTIONS: Elucidation of the mechanisms underlying the cellular responses to
      HZE particles, particularly under reduced gravity and situations of exposure to
      additional radiations, such as protons, should be useful in reducing the
      uncertainty associated with current models for predicting long-term health risks
      of space radiation. These studies are also relevant to hadron therapy of cancer.

PMID- 24111932
TI  - Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma.
AB  - Multiple myeloma (MM) is a haematological malignancy characterized by the
      accumulation of clonal plasma cells (PCs) in the bone marrow (BM). Although novel
      therapeutic strategies have prolonged survival of patients, the disease remains
      difficult to treat with a high risk of relapse. The failure of therapy is thought
      to be associated with a persistent population of the so-called MM stem cells or
      myeloma initiating cells (MIC) that exhibit tumour-initiating potential, self
      renewal and resistance to chemotherapy. However, the population responsible for
      the origin and sustainability of tumour mass has not been clearly characterized
      so far. This review summarizes current myeloma stem cell concepts and suggests
      that high phenotypic and intra-clonal heterogeneity, together with plasticity
      potential of MM might be other contributing factors explaining discrepancies
      among particular concepts and contributing to the treatment failure. 

PMID- 24111933
TI  - Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a
      staged approach: a report from the International League Against Epilepsy
      Nonepileptic Seizures Task Force.
AB  - An international consensus group of clinician-researchers in epilepsy, neurology,
      neuropsychology, and neuropsychiatry collaborated with the aim of developing
      clear guidance on standards for the diagnosis of psychogenic nonepileptic
      seizures (PNES). Because the gold standard of video electroencephalography (vEEG)
      is not available worldwide, or for every patient, the group delineated a staged
      approach to PNES diagnosis. Using a consensus review of the literature, this
      group evaluated key diagnostic approaches. These included: history, EEG,
      ambulatory EEG, vEEG/monitoring, neurophysiologic, neurohumoral, neuroimaging,
      neuropsychological testing, hypnosis, and conversation analysis. Levels of
      diagnostic certainty were developed including possible, probable, clinically
      established, and documented diagnosis, based on the availability of history,
      witnessed event, and investigations, including vEEG. The aim and hope of this
      report is to provide greater clarity about the process and certainty of the
      diagnosis of PNES, with the intent to improve the care for people with epilepsy
      and nonepileptic seizures. 

PMID- 24111934
TI  - Topology of the electron density of d0 transition metal compounds at subatomic
      resolution.
AB  - Accurate X-ray diffraction experiments allow for a reconstruction of the electron
      density distribution of solids and molecules in a crystal. The basis for the
      reconstruction of the electron density is in many cases a multipolar expansion of
      the X-ray scattering factors in terms of spherical harmonics, a so-called
      multipolar model. This commonly used ansatz splits the total electron density of
      each pseudoatom in the crystal into (i) a spherical core, (ii) a spherical
      valence, and (iii) a nonspherical valence contribution. Previous studies, for
      example, on diamond and alpha-silicon have already shown that this approximation
      is no longer valid when ultrahigh-resolution diffraction data is taken into
      account. We report here the results of an analysis of the calculated electron
      density distribution in the d(0) transition metal compounds [TMCH3](2+) (TM = Sc,
      Y, and La) at subatomic resolution. By a detailed molecular orbital analysis, it
      is demonstrated that due to the radial nodal structure of the 3d, 4d, and 5d
      orbitals involved in the TM-C bond formation a significant polarization of the
      electron density in the inner electronic shells of the TM atoms is observed. We
      further show that these polarizations have to be taken into account by an
      extended multipolar model in order to recover accurate electron density
      distributions from high-resolution structure factors calculated for the title
      compounds. 

PMID- 24111935
TI  - Clinicopathologic analysis of 66 Japanese thin melanomas with metastasis of
      sentinel or regional lymph node.
AB  - BACKGROUND: Assessment of sentinel lymph node status is commonly performed in the
      treatment of cutaneous melanoma. However, there are no definite guidelines for
      thin melanomas with Breslow tumor thickness <1.0 mm, in part because thin
      melanomas are relatively infrequently positive for lymph node metastasis.
      METHODS: We analyzed the clinicopathologic relationship among tumor thickness,
      mitotic index, tumor infiltrating lymphocytes (TIL), tumor size, regional lymph
      node metastasis and prognosis in 66 Japanese patients with thin melanomas.
      Immunohistochemical evaluations for TIL were also performed. RESULTS: Thirty-one
      of the 66 melanomas were Clark level I without lymph node metastasis (0/31, 0%).
      In tumors of Clark level II or higher (35/66), there were five (14%) regional
      lymph node metastasis. Melanomas with two or more mitoses in 1 mm(2) per high
      power fields showed higher frequencies of lymph node metastasis (2/3, 67%),
      compared to those with fewer than two mitoses (3/32, 9%). Tumors with intensive
      TIL that partially or completely surrounded the tumor revealed higher frequencies
      of lymph node metastasis (5/28, 18%), compared to those with none or slight TIL
      (0/7, 0%). The main components of TIL were CD8-positive T lymphocytes. No
      metastasized tumors were under 2.0 cm(2) . CONCLUSIONS: The presence of mitotic
      activity, large tumor size and an intense lymphocytic infiltrate should prompt
      sentinel lymph node biopsy in thin melanomas.

PMID- 24111936
TI  - Surface state of sacrificial copper electrode by electropolishing in hydrophobic
      ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide.
AB  - Anodic dissolution of natural surface-oxidized, air-annealed, cathodically
      reduced, and cathodically deposited copper in hydrophobic ionic liquid 1-buthyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide under galvanostatic
      conditions by means of gravimetric measurements was studied. The resulting
      samples were mirror-like oxide-free copper pattern. The mechanism of the
      electropolishing of oxidized copper surface was considered. The consequent anodic
      reactions Cu2O - 1e = Cu(+) + CuO, CuO - 2e = Cu(2+) + O, and Cu - 1e = Cu(+)
      take place. The electropolishing itself occurs over oxygen-free copper surface
      due to competitive residual water discharge in the pits and copper dissolution on
      the roughness. 

PMID- 24111937
TI  - Multicomponent reactions for de novo synthesis of BODIPY probes: in vivo imaging
      of phagocytic macrophages.
AB  - Multicomponent reactions are excellent tools to generate complex structures with
      broad chemical diversity and fluorescent properties. Herein we describe the
      adaptation of the fluorescent BODIPY scaffold to multicomponent reaction
      chemistry with the synthesis of BODIPY adducts with high fluorescence quantum
      yields and good cell permeability. From this library we identified one BODIPY
      derivative (PhagoGreen) as a low-pH sensing fluorescent probe that enabled
      imaging of phagosomal acidification in activated macrophages. The fluorescence
      emission of PhagoGreen was proportional to the degree of activation of
      macrophages and could be specifically blocked by bafilomycin A, an inhibitor of
      phagosomal acidification. PhagoGreen does not impair the normal functions of
      macrophages and can be used to image phagocytic macrophages in vivo. 

PMID- 24111938
TI  - The study of marketed and experimental formulation approaches enabling site
      specific delivery of mesalamine in patients with inflammatory bowel disease.
AB  - This patent review focuses exclusively on the oral delivery of mesalamine (5-ASA)
      and excludes oral mesalamine pro-drug and rectal delivery formulations. The
      formulation strategies of marketed formulations (Apriso((r)), Asacol((r)),
      Lialda((r)) and Pentasa((r))) and non-marketed formulations are reviewed and
      explained by decoding formulation specifics that enable the site specific
      delivery for the treatment of inflammatory bowel disease. 

PMID- 24111939
TI  - Characterization of UV-screening compounds, mycosporine-like amino acids, and
      scytonemin in the cyanobacterium Lyngbya sp. CU2555.
AB  - Ultraviolet-screening compounds from the cyanobacterium Lyngbya sp. CU2555 were
      partially characterized and investigated for their induction by UV radiation,
      stability under different abiotic factors, and free radical scavenging activity.
      Based on the high-performance liquid chromatography coupled with diode array
      detector and ion trap liquid chromatography/mass spectrometry analysis, the
      compounds were identified as palythine (UVlambda max: 319 nm; m/z: 245), asterina
      (UVlambda max: 330 nm; m/z: 289), scytonemin (UVlambda max: 384 nm; mw: 544), and
      reduced scytonemin (UVlambda max: 384 nm; m/z: 547). This is the first report for
      the occurrence of palythine, asterina, and an unknown mycosporine-like amino
      acids (MAA), M-312 (UVlambda max: 312 +/- 1 nm), in addition to scytonemin and
      reduced scytonemin in Lyngbya strains studied so far. Induction of MAAs and
      scytonemin was significantly more prominent upon exposure to UV-A + UV-B
      radiation. Both MAAs and scytonemin were highly resistant to some physicochemical
      factors such as UV-B, heat, and a strong oxidizing agent and exhibited strong
      antioxidant activity. These results indicate that the studied cyanobacterium may
      protect itself from deleterious short-wavelength radiation by synthesizing
      photoprotective compounds in response to harmful UV radiation.

PMID- 24111940
TI  - Changes in BMI and waist circumference among primary and secondary school
      students from 2005 to 2010 in Anhui, China.
AB  - AIM: To examine the change in Body Mass Index (BMI) and waist circumference (WC)
      among primary and secondary school students aged 7-18 in Anhui Province between
      2005-2010. SUBJECTS AND METHODS: A total of 15 812 primary and secondary school
      students aged 7-18 were included in two national surveys on students'
      constitution and health in 2005 and 2010 in Anhui Province. Measurements of
      height, weight and WC were taken by trained investigators. BMI was calculated for
      each subject. RESULTS: The mean BMI and WC were significantly increased from 2005
      to 2010. For boys, mean increases were 0.85 kg/m(2) and 2.01 cm or 0.08 and 0.34
      SD score units, while for girls those were 0.39 kg/m(2) and 2.10 cm or 0.20 and
      0.39 SD score units (all p < 0.001). The standard deviation scores for WC
      increased much more than for BMI (0.34 units vs 0.08 units for boys and 0.39
      units vs 0.20 units for girls). CONCLUSIONS: The average value of BMI and WC
      among primary and secondary school students has increased dramatically from 2005
      to 2010 in Anhui, China. Changes in WC have greatly exceeded those in BMI,
      showing that WC is a good proxy for central fatness rather than BMI.

PMID- 24111941
TI  - Time-based prospective memory in young children-Exploring executive functions as
      a developmental mechanism.
AB  - The present study investigated time-based prospective memory (PM) during the
      transition from kindergarten/preschool to school age and applied mediation models
      to test the impact of executive functions (working memory, inhibitory control)
      and time monitoring on time-based PM development. Twenty-five preschool (age: M =
      5.75, SD = 0.28) and 22 primary school children (age: M = 7.83, SD = 0.39)
      participated. To examine time-based PM, children had to play a computer-based
      driving game requiring them to drive a car on a road without hitting others cars
      (ongoing task) and to refill the car regularly according to a fuel gauge, which
      serves as clock equivalent (PM task). The level of gas that was still left in the
      fuel gauge was not displayed on the screen and children had to monitor it via a
      button press (time monitoring). Results revealed a developmental increase in time
      based PM performance from preschool to school age. Applying the mediation models,
      only working memory was revealed to influence PM development. Neither inhibitory
      control alone nor the mediation paths leading from both executive functions to
      time monitoring could explain the link between age and time-based PM. Thus,
      results of the present study suggest that working memory may be one key cognitive
      process driving the developmental growth of time-based PM during the transition
      from preschool to school age.

PMID- 24111942
TI  - Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3
      d]pyrimidine antifolates via cellular uptake by folate receptor alpha and
      inhibition of de novo purine nucleotide biosynthesis.
AB  - A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d
      with varying chain lengths (n = 5-8) was designed and synthesized as part of our
      program to provide targeted antitumor agents with folate receptor (FR) cellular
      uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase)
      inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and
      reacted with diazomethane, followed by 48% HBr to generate the alpha
      bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with
      5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and
      subsequent coupling with diethyl l-glutamate and saponification afforded target
      compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FRalpha and 
      beta, associated with high affinity binding and inhibition of de novo purine
      nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR
      expressing Chinese hamster cells and human KB tumor cells in culture. Our studies
      establish, for the first time, that a side chain benzoyl group is not essential
      for tumor-selective drug uptake by FRalpha. 

PMID- 24111945
TI  - Unilateral widespread lichen planus following Blaschko's lines after Mycoplasma
      pneumoniae infection.

PMID- 24111944
TI  - High rates of lifetime and recent violence observed among harder-to-reach women
      living with HIV.
AB  - This study examined the prevalence and correlates associated with lifetime and
      recent violence among a sample of harder-to-reach human immunodeficiency virus
      (HIV)-positive women living in British Columbia (BC), Canada. Interviewer-led
      surveys with 1000 participants gathered quantitative data on social, economic,
      and structural characteristics such as housing status, relationship status,
      family structure, history of drug use, and sexual behavior. Logistic regression
      analysis modeled associations between independent variables and experiences of
      violence at baseline. Cox regression analyses with time-dependent covariates
      determined correlates of lifetime and recent violence among HIV-positive women.
      Of the 249 women in the study, an overwhelming proportion of women (81%) reported
      experiences of violence in their lifetime. Among those, 22% reported recent
      experiences of violence, and 56% of the women reported more than five violent
      episodes in their lifetime. Lifetime violence was independently associated with
      HIV-related stigma (adjusted odds ratio [AOR] = 2.18, 95% confidence interval
      [CI] = 1.14-5.70), previous tobacco use (AOR = 2.79, 95% CI = 1.10-7.07), ever
      having a drinking problem (AOR = 2.82, 95% CI = 1.28-6.23), and ever having
      received care for a mental health condition (AOR = 2.42, 95% CI = 1.06-5.52).
      Recent violence was associated with the current illicit drug use (AOR = 2.60, 95%
      CI = 1.14-5.90), and currently residing in unstable housing (AOR = 2.75, 95% CI =
      1.31-5.78). This study underscores the need to consider potential experiences of
      historical and current violence as part of comprehensive care for women living
      with HIV. 

PMID- 24111943
TI  - Methionine down-regulates TLR4/MyD88/NF-kappaB signalling in osteoclast
      precursors to reduce bone loss during osteoporosis.
AB  - BACKGROUND AND PURPOSE: Studies have demonstrated that a moderate intake of amino
      acids is associated with development of bone health. Methionine, a sulphur
      containing essential amino acid, has been largely implicated for improving
      cartilage formation, however its physiological significance on bone integrity and
      functionality have not been elucidated. We investigated whether methionine can
      prevent osteoporotic bone loss. EXPERIMENTAL APPROACH: The anti-resorptive effect
      of methionine, (250 mg kg(-1) body wt administered in drinking water for 10
      weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone
      turnover, formation of osteoclasts from blood-derived mononuclear cells and
      changes in the synthesis of pro-osteoclastogenic cytokines. KEY RESULTS:
      Methionine improved bone density and significantly decreased the degree of
      osteoclast development from blood mononuclear cells in OVX rats, as indicated by
      decreased production of osteoclast markers tartarate resistant acid phosphatase b
      (TRAP5b) and MIP-1alpha. siRNA-mediated knockdown of myeloid differentiation
      primary response 88 [MyD88], a signalling molecule in the toll-like receptor
      (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1alpha
      in developing osteoclasts. Methionine supplementation disrupted osteoclast
      development by inhibiting TLR-4/MyD88/NF-kappaB pathway. CONCLUSIONS AND
      IMPLICATIONS: TLR-4/MyD88/NF-kappaB signalling pathway is integral for osteoclast
      development and this is down-regulated in osteoporotic system on methionine
      treatment. Methionine treatment could be beneficial for the treatment of
      postmenopausal osteoporosis.

PMID- 24111946
TI  - Phosphorylation of neuronal Lysine-Specific Demethylase 1LSD1/KDM1A impairs
      transcriptional repression by regulating interaction with CoREST and histone
      deacetylases HDAC1/2.
AB  - Epigenetic mechanisms play important roles in brain development, orchestrating
      proliferation, differentiation, and morphogenesis. Lysine-Specific Demethylase 1
      (LSD1 also known as KDM1A and AOF2) is a histone modifier involved in
      transcriptional repression, forming a stable core complex with the corepressors
      corepressor of REST (CoREST) and histone deacetylases (HDAC1/2). Importantly, in
      the mammalian CNS, neuronal LSD1-8a, an alternative splicing isoform of LSD1
      including the mini-exon E8a, sets alongside LSD1 and is capable of enhancing
      neurite growth and morphogenesis. Here, we describe that the morphogenic
      properties of neuronal LSD1-8a require switching off repressive activity and this
      negative modulation is mediated in vivo by phosphorylation of the Thr369b residue
      coded by exon E8a. Three-dimensional crystal structure analysis using a phospho
      mimetic mutant (Thr369bAsp), indicate that phosphorylation affects the residues
      surrounding the exon E8a-coded amino acids, causing a local conformational
      change. We suggest that phosphorylation, without affecting demethylase activity,
      causes in neurons CoREST and HDAC1/2 corepressors detachment from LSD1-8a and
      impairs neuronal LSD1-8a repressive activity. In neurons, Thr369b phosphorylation
      is required for morphogenic activity, converting neuronal LSD1-8a in a dominant
      negative isoform, challenging LSD1-mediated transcriptional repression on target
      genes. 

PMID- 24111947
TI  - Examining elementary school children's level of enjoyment of traditional tag
      games vs. interactive dance games.
AB  - Enjoyment has been implicated as a determinant of physical activity among
      children and adolescents. However, the effect of different sport activities on
      children's enjoyment remains largely unexplored. This study examined whether
      children's enjoyment in physical education (PE) varied as a function of learning
      activities. Participants were 210 third- through sixth-grade children who had a
      30 min PE class every week. Participants responded to a standardized self-report
      enjoyment survey measuring their enjoyment level in a PE class during which they
      participated in tag games. Students completed the same questionnaire when
      involved in interactive dance games in PE. The results revealed that children
      reported significantly higher scores in enjoyment toward interactive dance games
      than they did toward traditional games (p < .01). Also, girls exhibited higher
      enjoyment toward interactive dance games than boys did (p < .05). However, no
      gender difference emerged on enjoyment toward traditional games. In conclusion,
      it is practical and meaningful to integrate interactive dance games into PE.

PMID- 24111948
TI  - The complex ontogenetic trajectory of mandibular shape in a laboratory mouse.
AB  - The mouse mandible is a popular model system that continues to be the focus of
      studies in evo-devo and other fields. Yet, little attention has been given to the
      role of postnatal growth in producing the adult form. Using cleared and stained
      specimens, we describe the timing of tooth and jaw development and changes in jaw
      size and shape from postnatal day 1 (p1) through weaning to adulthood. We found
      that tooth development is relatively advanced at birth, and that the functional
      adult dentition is in place by p15 (just before the start of weaning). Shape
      analysis showed that the trajectory of mandible shape changes direction at least
      twice between birth and adulthood, at p7 and p15. At each stage there are changes
      in shape to all tooth- and muscle-bearing regions and, at each change of
      direction, all of these regions change their pattern of growth. The timing of the
      changes in direction in Mus suggests there are signals that redirect growth
      patterns independently of changes in function and loading associated with weaning
      and jaw muscle growth. A better understanding of these signals and how they
      produce a functionally integrated mandible may help explain the mechanisms
      guiding evolutionary trends and patterns of plasticity and may also provide
      valuable clues to therapeutic manipulation of growth to alleviate the
      consequences of trauma or disease. 

PMID- 24111949
TI  - General practice-recorded depression and antidepressant use in young people with
      newly diagnosed Type 1 diabetes: a cohort study using the Clinical Practice
      Research Datalink.
AB  - AIMS: To investigate whether young people with Type 1 diabetes have an increased
      rate of depression and antidepressant use and whether their risk varies by age
      group, time from diabetes diagnosis, calendar period of diagnosis or
      complications status. METHODS: A cohort of incident cases of patients with Type 1
      diabetes diagnosed before 35 years of age (n = 5548) was identified within the
      Clinical Practice Research Datalink and individually age and sex matched with up
      to two control subjects without diabetes (n = 10 657). Patients with depression
      were identified through general practice-recorded depression codes and
      antidepressant prescriptions. Cox regression models gave hazard ratios for
      depression in people with Type 1 diabetes compared with control subjects.
      RESULTS: People with Type 1 diabetes were twice as likely to have a record of
      antidepressant use and general practice-diagnosed depression as their matched
      control subjects (hazard ratio 2.08, 95% CI 1.73-2.50, P < 0.001). These
      associations varied by time from diagnosis, with marked increases observed within
      the first 5 years of diagnosis (hazard ratio 2.14, 95% CI 1.51-3.03, P < 0.001),
      and by age at diabetes diagnosis, with excesses noted even in the 10- to 19-year
      age group (hazard ratio 1.45, 95% CI 1.06-1.98, P = 0.02). CONCLUSIONS: This
      population-based study shows that people with Type 1 diabetes have higher rates
      of general practice-recorded depression and antidepressant use. The excess is
      present within 5 years of diabetes diagnosis, suggesting psychological input for
      patients is warranted in the early years of their condition.

PMID- 24111950
TI  - The applicability of ambulatory electroencephalography (AEEG) in healthy horses
      and horses with abnormal behaviour or clinical signs of epilepsy.
AB  - BACKGROUND: Short-duration electroencephalography (EEG) recordings in horses are
      helpful in diagnosing intracranial disorders. Potentially, long-duration
      ambulatory EEG (AEEG) recordings in horses will enhance the chance of detecting
      abnormal brain activity independent of the presence of an insult. OBJECTIVE: The
      objective of this study was to test if AEEG recordings in unsedated horses can be
      acquired and benefit diagnosing abnormal brain activity. ANIMALS AND METHODS:
      Recordings were taken from 8 adult control horses and 10 patients suspected of
      intracranial abnormalities. Self-adhesive electrodes and the 'Porti-5' recording
      system were used. Filter settings were 0.5 Hz high pass and 35 Hz low pass. The
      records were analysed offline at a 50-200 MUV/division and 10 seconds/division
      scale. Abnormal activity was defined as a spike or sharp wave, a period of
      generalised slow wave rhythmical activity or a generalised fast rhythmical
      discharge. The recording time ranged from 5 to 49 hours. RESULTS: In the control
      group, one horse showed pathological activity. In the patient group, six out of
      nine horses showed abnormal activity during the recordings. Magnetic resonance
      imaging confirmed the presence of an intracranial mass in one patient. Long-term
      recordings of high quality can be obtained in unsedated horses by allowing daily
      activity using AEEG, resulting in a reasonable chance of recording (inter)ictal
      abnormal brain activity indicating epileptic or seizure-like activity in the
      absence of clinical signs or seizures. CONCLUSIONS: It is concluded that abnormal
      behaviour can be expressed intermittently, and with the availability of AEEG a
      useful tool is added to the diagnostic scenario for horses.

PMID- 24111951
TI  - Akt inhibitor MK2206 selectively targets CLL B-cell receptor induced cytokines,
      mobilizes lymphocytes and synergizes with bendamustine to induce CLL apoptosis.

PMID- 24111971
TI  - Readiness for and predictors of evidence-based practice of acute-care nurses: a
      cross-sectional postal survey.
AB  - BACKGROUND: Nurses' adoption of evidence-based practice (EBP) remains limited
      although most nurses are familiar with EBP and belief in its value for patient
      care. Efforts to accelerate nurses' EBP activities have met with limited success.
      Knowledge of predictors of nurses' EBP activities is lacking. AIMS: To describe
      nurses' readiness for EBP as measured by their information needs, skills in using
      electronic bibliographical databases (EBDs) and awareness of available EBP-needed
      resources; EBP beliefs and frequency of EBP activities, and identify predictors
      of EBP activities and beliefs. METHODS: This was a cross-sectional survey,
      distributed to a homogeneous, consecutive sample of 546 acute-care nurses.
      Response rate was 64.3%; responses from direct-care nurses (n = 298) and
      administrators (n = 45) were analysed. Descriptive statistics were used to
      describe readiness for EBP, frequency of certain EBP activities and EBP beliefs.
      Logistic regression analyses were performed to identify predictors of EBP
      activities and multiple regression analysis to identify predictors of EBP
      beliefs. RESULTS: The nurses generally seldom participated in the EBP activities
      studied, in spite of familiarity with and positive beliefs towards EBP. Evidence
      based practice beliefs predicted all three activities studied. Skills in using
      EBDs predicted information-seeking and evaluating research. Awareness of
      available EBP-needed resources predicted information-seeking, role predicted
      evaluating research, while familiarity with EBP predicted using research in
      practice. Six predictors explained nearly 40% of the variance in EBP beliefs.
      CONCLUSIONS: Nurses' EBP activities must be facilitated and accelerated. The
      findings provide empirical support to the primacy of EBP beliefs in nurses'
      engagement in EBP and of the complexity of EBP. While the identified predictors
      of EBP activities and beliefs are susceptible to change, diverse strategies are
      needed to influence each one. Strategies should focus on influencing EBP beliefs,
      that is, by increasing skills in using EBDs, discussion about EBP in the clinical
      environment and familiarity with EBP.

PMID- 24111970
TI  - Transcriptional control of antioxidant defense by the circadian clock.
AB  - SIGNIFICANCE: The circadian clock, an internal timekeeping system, is implicated
      in the regulation of metabolism and physiology, and circadian dysfunctions are
      associated with pathological changes in model organisms and increased risk of
      some diseases in humans. RECENT ADVANCES: Data obtained in different organisms,
      including humans, have established a tight connection between the clock and
      cellular redox signaling making it among the major candidates for a link between
      the circadian system and physiological processes. CRITICAL ISSUES: In spite of
      the recent progress in understanding the importance of the circadian clock in the
      regulation of reactive oxygen species homeostasis, molecular mechanisms and key
      regulators are mostly unknown. FUTURE DIRECTIONS: Here we review, with an
      emphasis on transcriptional control, the circadian-clock-dependent control of
      oxidative stress response system as a potential mechanism in age-associated
      diseases. We will discuss the roles of the core clock components such as brain
      and muscle ARNT-like 1, Circadian Locomotor Output Cycles Kaput, the circadian
      clock-controlled transcriptional factors such as nuclear factor erythroid-2
      related factor, and peroxisome proliferator-activated receptor and circadian
      clock control chromatin modifying enzymes from sirtuin family in the regulation
      of cellular and organism antioxidant defense.

PMID- 24111973
TI  - Abscisic acid alleviates iron deficiency by promoting root iron reutilization and
      transport from root to shoot in Arabidopsis.
AB  - Abscisic acid (ABA) has been demonstrated to be involved in iron (Fe)
      homeostasis, but the underlying mechanism is largely unknown. Here, we found that
      Fe deficiency induced ABA accumulation rapidly (within 6 h) in the roots of
      Arabidopsis. Exogenous ABA at 0.5 MUM decreased the amount of root apoplastic Fe
      bound to pectin and hemicellulose, and increased the shoot Fe content
      significantly, thus alleviating Fe deficiency-induced chlorosis. Exogenous ABA
      promoted the secretion of phenolics to release apoplastic Fe and up-regulated the
      expression of AtNRAMP3 to enhance reutilization of Fe stored in the vacuoles,
      leading to a higher level of soluble Fe and lower ferric-chelate reductase (FCR)
      activity in roots. Treatment with ABA also led to increased Fe concentrations in
      the xylem sap, partially because of the up-regulation of AtFRD3, AtYSL2 and
      AtNAS1, genes related to long-distance transport of Fe. Exogenous ABA could not
      alleviate the chlorosis of abi5 mutant resulting from the significantly low
      expression of AtYSL2 and low transport of Fe from root to shoot. Taken together,
      our data support the conclusion that ABA is involved in the reutilization and
      transport of Fe from root to shoot under Fe deficiency conditions in Arabidopsis.

PMID- 24111974
TI  - A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector
      administered by caregivers to patients with epilepsy who require intermittent
      intervention for acute repetitive seizures.
AB  - PURPOSE: A diazepam auto-injector (AI) has been developed for intramuscular
      administration to treat acute repetitive seizures (ARS). The objective of this
      study was to evaluate the efficacy and safety of the diazepam AI when
      administered by caregivers to control an episode of ARS. METHODS: In this phase
      III, randomized, double-blind, parallel-group, placebo-controlled, multicenter
      study, subjects with epilepsy on a stable antiepileptic drug regimen who required
      intermittent medical intervention to control ARS were randomized 1:1 to the
      placebo AI or the diazepam AI group. Subjects were stratified according to age (2
      5, 6-11, >=12 years). Dose (5, 10, 15, or 20 mg) was based on age and weight. A
      single dose of study medication was dispensed to be administered by caregivers in
      an outpatient setting when required. The primary end point was time to next
      seizure or rescue from 15 min to 12 h postdose. Secondary end points included
      rescue medication use, number of seizures postdose, caregiver and physician
      treatment assessments, and safety measures. KEY FINDINGS: Of 234 subjects
      randomized, 81/110 in the placebo AI group and 82/124 in the diazepam AI group
      were included in the intent-to-treat analysis. Baseline characteristics were
      similar for both groups. Time to next seizure or rescue was significantly longer
      in the diazepam AI group compared with the placebo AI group, with a hazard ratio
      of 0.55 (95% confidence interval (CI) 0.34-0.88; p = 0.012) for diazepam AI
      versus placebo AI, adjusted for age group. The 25th percentile for time to the
      next seizure or rescue was 1.18 h (95% CI 0.38-2.03) for placebo AI and 2.70 h
      (95% CI 0.48-11.42) for diazepam AI; the median was 5.9 h for placebo AI and was
      inestimable for diazepam AI due to the low number of events experienced by
      subjects in that group. The proportion of subjects using rescue medication
      postdose was 30% (24/81) placebo AI versus 17% (14/82) diazepam AI (p = 0.066).
      An event (seizure or rescue) occurred in 55.6% of subjects in the placebo AI
      group and 35.4% in the diazepam AI group. The number of seizures experienced
      during the 12-h postdose period was significantly lower for diazepam AI (median
      0.0) compared with placebo AI (median 1.0; p = 0.010). Treatment-emergent adverse
      events (TEAEs) were reported in 44% (35/79) of subjects in the placebo AI group
      and 42% (34/81) in the diazepam AI group. The most common TEAEs reported were
      injection site pain (15% placebo AI, 17% diazepam AI) and injection site
      hemorrhage (6% placebo AI, 5% diazepam AI). SIGNIFICANCE: The diazepam AI was
      significantly more effective than placebo AI at delaying the next seizure or
      rescue. Secondary efficacy end points were generally supportive of the primary
      outcome. Diazepam AI administered by trained caregivers was effective for the
      treatment of ARS and was well-tolerated, with a safety profile similar to
      placebo.

PMID- 24111975
TI  - Dark formation of hydroxyl radical in Arctic soil and surface waters.
AB  - Hydroxyl radical (*OH) is a highly reactive and unselective oxidant in
      atmospheric and aquatic systems. Current understanding limits the role of DOM
      produced *OH as an oxidant in carbon cycling mainly to sunlit environments where
      *OH is produced photochemically, but a recent laboratory study proposed a
      sunlight-independent pathway in which *OH forms during oxidation of reduced
      aquatic dissolved organic matter (DOM) and iron. Here we demonstrate this non
      photochemical pathway for *OH formation in natural aquatic environments. Across a
      gradient from dry upland to wet lowland habitats, *OH formation rates increase
      with increasing concentrations of DOM and reduced iron, with highest *OH
      formation predicted at oxic-anoxic boundaries in soil and surface waters.
      Comparison of measured vs expected electron release from reduced moieties
      suggests that both DOM and iron contribute to *OH formation. At landscape scales,
      abiotic DOM oxidation by this dark *OH pathway may be as important to carbon
      cycling as bacterial oxidation of DOM in arctic surface waters. 

PMID- 24111976
TI  - Association between underweight and taste sensitivity in middle- to old-aged
      nursing home residents in Sri Lanka: a cross-sectional study.
AB  - Low taste sensitivity may be one factor related to undernutrition, which is a
      major problem in developing countries. The purpose of this cross-sectional study
      was to examine the association between underweight, one indicator of
      undernutrition, and taste sensitivity in middle- to old-aged Sri Lankan nursing
      home residents. Participants were 946 residents with BMI of <25.0 from 25 nursing
      homes. Data were obtained on height, weight, taste sensitivity, subjective taste
      ability, sex, age, ethnicity, number of years in nursing homes, activities of
      daily living (ADL), frequency of exercise, bowel movements, smoking status,
      drinking status, current number of chronic diseases, number and kinds of
      medications used, self-reporting questionnaire 20 (SRQ20), subjective smell
      ability, number of teeth present, Eichner index and flow rate of saliva. Low
      sensitivity to bitter taste, being male, old age, low ADL, smoking experience,
      drinking experience, fewer medications used and no use of medication for
      hypertension and diabetes were each associated with underweight (P < 0.05). In a
      multilevel Poisson regression model adjusted for sex, age, ADL, smoking status,
      drinking status, number of medications used, use of medication for hypertension
      and diabetes and flow rate of saliva, subjects with low sensitivity (>0.003%
      quinine hydrochloride dihydrate) to bitter taste had a significant 1.70 times
      higher prevalence ratio (95% confident interval 1.04-2.80) for underweight
      compared with those with high sensitivity (0.0001% quinine hydrochloride
      dihydrate). These results suggest that low taste sensitivity to bitter taste may
      be one factor related to underweight. 

PMID- 24111977
TI  - Rovibrational states of N3- and CO2 up to high J: a theoretical study beyond fc
      CCSD(T).
AB  - An accurate near-equilibrium potential energy surface (PES) has been constructed
      for the azide ion (N(3)(-)) on the basis of coupled cluster calculations up to
      CCSDTQ (Kallay, M.; Surjan, P. R. J. Chem. Phys. 2001, 115, 2945.), with
      contributions from inner-shell correlation and special relativity being taken
      into account as well. A larger number of rovibrational states has been
      investigated by variational calculations with Watson's isomorphic Hamiltonian for
      linear molecules. Analogous calculations for CO2 demonstrate the high quality of
      this type of calculations. The G(v) values of the symmetric stretching and
      bending vibration of 14N(3)(-) are predicted to be nu1 = 1307.9 cm(-1) and nu2 =
      629.3 cm(-1), with an uncertainty of ca. 1 cm(-1). Fermi resonance is less
      pronounced for the lower polyads of 14N(3)(-) compared with 12C16O2 but is as
      strong as in CO2 for the lowest diad of isotopologue 15-14-15. The band origin of
      the antisymmetric stretching vibration of 14N(3)(-) is calculated to be nu3 =
      1986.4 cm(-1), only 0.1 cm(-1) lower than the experimental value. The
      corresponding vibrational transition dipole moment is predicted to be as large as
      MU = 0.476 D, 46% higher than calculated for CO2. The perturbed combination tone
      (01(1)1), which was accessible through diode laser IR spectroscopy, undergoes
      anharmonic interaction with at least two other vibrational states.

PMID- 24111978
TI  - Synthesis of Zinc Chlorophyll Homo/Hetero-Dyads and their Folded Conformers with
      Porphyrin, Chlorin, and Bacteriochlorin pi-Systems.
AB  - Zinc complex of pyropheophorbide-b, a derivative of chlorophyll-b, was covalently
      dimerized through ethylene glycol diester. The synthetic homo-dyad was axially
      ligated with two methanol molecules from the beta-face and both the
      diastereomerically coordinating methanol species were hydrogen bonded with the
      keto-carbonyl groups of the neighboring chlorin in a complex. The resulting
      folded conformer in a solution was confirmed by visible, (1) H NMR and IR
      spectra. All the synthetic zinc chlorin homo- and hetero-dyads consisting of
      pyropheophorbides-a, b and/or d took the above methanol-locked and pi-pi stacked
      supramolecules in 1% (v/v) methanol and benzene to give redmost (Qy) electronic
      absorption band(s) at longer wavelengths than those of the corresponding
      monomeric chlorin composites. The other zinc chlorin and bacteriochlorin homo
      dyads completely formed similar folded conformers in the same solution, while
      zinc inverse chlorin and porphyrin homo-dyads partially took such supramolecules.
      The J-type aggregation to folded conformers and the redshift values of composite
      Qy bands were dependent on the electronic and steric factors of porphyrinoid
      moieties in dyads.

PMID- 24111979
TI  - Multi-level modelling of physical activity in nuclear families.
AB  - BACKGROUND: Few studies focus on the different dyadic relations among family
      members to study physical activity (PA) levels. AIM: The aim was to investigate
      predictors and sources of variance of PA levels in nuclear families using multi
      level modelling. SUBJECTS AND METHODS: The sample consisted of 2661 Portuguese
      four-member nuclear families (10 644 subjects). PA was measured using a
      questionnaire and socioeconomic status (SES) was assessed by parental occupation.
      Height and weight were measured in children, while parents self-reported their
      values. RESULTS: The results showed that intra-generational similarities were
      higher than inter-generational, with correlation values of 0.26 and 0.10,
      respectively. SES was unrelated to any family members' PA level. Being male (beta
      = 0.26, t = 21.77), being older (beta = -0.36, t = -4.73) and greater BMI for
      mothers (beta = 0.02, t = 2.55) had effects on individuals' PA. CONCLUSION: These
      results suggest a strong dyadic resemblance in PA, showed different effects of
      gender, age and BMI on individuals' PA and demonstrated that multi-level
      modelling is a useful strategy to study PA in families.

PMID- 24111981
TI  - Hematological and cardiometabolic safety of clozapine in the treatment of very
      early onset schizophrenia: a retrospective chart review.
AB  - OBJECTIVE: There are very few studies in the literature regarding clozapine use
      in children <13 years of age. In this retrospective chart review, we compared the
      safety of clozapine--as determined by hematological and cardiometabolic changes -
      to that of non-clozapine antipsychotics used in the treatment of childhood-onset
      schizophrenia (COS). METHODS: The clozapine treatment group (CTG) consisted of 17
      COS patients (mean age 10.4 +/- 2 years) who were hospitalized in a psychiatric
      ward between the years 2005 and 2012. The control group consisted of 19 COS
      patients (mean age 10.1 +/- 1.4 years) who were hospitalized in the same ward
      during the same time period, and were treated with non-clozapine antipsychotics.
      A retrospective chart review was conducted. Hematological (white blood cells,
      absolute neutrophil count [ANC], red blood cells, platelets), metabolic
      (aspartate transaminase, alanine transaminase, triglycerides, total cholesterol,
      bilirubin) and cardiac (heart rate) values were extracted from the medical
      charts. RESULTS: The average follow-up periods for the CTG and the control group
      were 332.9 +/- 200.5 days and 291.7 +/- 157 days, respectively. In the CTG,
      moderate neutropenia (ANC<1500/mm(3)) and mild neutropenia
      (1500/mm(3)<ANC<2000/mm(3)) were observed in two children (12%) and one child
      (6%), respectively. The neutropenia was transient in all cases. Treatment with
      clozapine was permanently discontinued only in one child (6%). There were no
      cases of agranulocytosis or severe infection in the CTG. In the control group,
      two children (11%) showed hematological abnormalities. Hyperlipidemia was
      observed in one child (6%) in the CTG at release from the hospital. Significantly
      more children (47%) in the CTG had tachycardia (heart rate>100 beats per minute)
      at release from the hospital, compared with only one child (5%) in the control
      group (p=0.006). CONCLUSIONS: It appears that clozapine use in very early onset
      schizophrenia is safe. Although hematological adverse effects did occur in our
      study, the rates were not much higher than those seen in the control group. We
      found that the hematological abnormalities in the CTG were mostly transient, and
      that treatment with clozapine can be safely continued or renewed.

PMID- 24111980
TI  - Efficacy, long-term safety, and tolerability of ziprasidone in children and
      adolescents with bipolar disorder.
AB  - OBJECTIVE: The purpose of this study was to evaluate the short- and long-term
      efficacy and safety of ziprasidone in children and adolescents with bipolar I
      disorder. METHODS: Subjects 10-17 years of age with a manic or mixed episode
      associated with bipolar I disorder participated in a 4 week, randomized, double
      blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open
      label extension study (OLE). Subjects were randomized 2:1 to initially receive
      flexible-dose ziprasidone (40-160 mg/day, based on weight) or placebo. Primary
      outcome was the change in Young Mania Rating Scale (YMRS) scores from baseline.
      Safety assessments included weight and body mass index (BMI), adverse events
      (AEs), vital signs, laboratory measures, electrocardiograms, and movement
      disorder ratings. RESULTS: In the RCT, 237 subjects were treated with ziprasidone
      (n=149; mean age, 13.6 years) or placebo (n=88; mean age, 13.7 years). The
      estimated least squares mean changes in YMRS total (intent-to-treat population)
      were -13.83 (ziprasidone) and -8.61 (placebo; p=0.0005) at RCT endpoint. The most
      common AEs in the ziprasidone group were sedation (32.9%), somnolence (24.8%),
      headache (22.1%), fatigue (15.4%), and nausea (14.1%). In the OLE, 162 subjects
      were enrolled, and the median duration of treatment was 98 days. The mean change
      in YMRS score from the end of the RCT to the end of the OLE (last observation
      carried forward) was -3.3 (95% confidence interval, -5.0 to -1.6). The most
      common AEs were sedation (26.5%), somnolence (23.5%), headache (22.2%), and
      insomnia (13.6%). For both the RCT and the OLE, no clinically significant mean
      changes in movement disorder scales, BMI z-scores, liver enzymes, or fasting
      lipids and glucose were observed. One subject on ziprasidone in the RCT and none
      during the OLE had Fridericia-corrected QT interval (QTcF) >= 460 ms. CONCLUSION:
      These results demonstrate that ziprasidone is efficacious for treating children
      and adolescents with bipolar disorder. Ziprasidone was generally well tolerated
      with a neutral metabolic profile. CLINICAL TRIALS REGISTRY: NCT00257166 and
      NCT00265330 at ClinicalTrials.gov.

PMID- 24111982
TI  - Associations among obesity, acute weight gain, and response to treatment with
      olanzapine in adolescent schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to investigate associations between body
      weight and illness characteristics, including weight gain and therapeutic
      efficacy, in adolescents with schizophrenia. METHODS: Adolescents ages 13-17
      years (n = 107) with American Psychiatric Association, Diagnostic and Statistical
      Manual of Mental Disorders, 4th ed. (DSM-IV) schizophrenia enrolled in a 6 week,
      double-blind, placebo-controlled trial comparing olanzapine and placebo.
      Therapeutic response was assessed by the Brief Psychiatric Rating Scale for
      Children (BPRS-C). Secondary outcomes included the Clinical Global Impressions
      Severity (CGI-S) scale and Positive and Negative Syndrome Scale (PANSS). Obesity
      was defined as sex-/age-adjusted body mass index (BMI) >= 95th percentile. Linear
      regression was used to analyze the relationship between weight gain and
      psychiatric symptom improvement; logistic regression was conducted to identify
      predictors of baseline obesity. RESULTS: Weight gain was significantly correlated
      with greater BPRS-C reduction among olanzapine-treated subjects (r = -0.31,
      p<0.01), whereas a trend was observed among placebo-treated subjects (r = -0.31,
      p = 0.08). However, this relationship became nonsignificant when analyses were
      controlled for duration of olanzapine treatment (p=0.12), and a treatment by
      weight gain interaction did not emerge in a repeated-measures mixed model
      analysis that included time in the study (t = 1.27, p = 0.21). Additionally,
      weight gain >= 7% was not significantly associated with response or remission.
      Among 17 adolescents (16%) with obesity at study entry, obesity was not
      significantly associated with endpoint BPRS-C illness severity. However, girls (p
      = 0.03), individuals hospitalized within the past year (p = 0.02), and those with
      less severe overall (p = 0.03) and negative symptoms (p = 0.003) according to the
      CGI-S and PANSS negative subscale, respectively, were more likely to be obese at
      baseline. CONCLUSION: Baseline obesity was associated with lower illness
      severity, which could be mediated by greater treatment adherence, leading to more
      weight gain. Olanzapine-related weight gain was not independently associated with
      symptomatic outcome when controlling for treatment duration. Additional studies
      are needed to extend these findings to other disorders and medications.

PMID- 24111983
TI  - Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled
      efficacy and long-term open-extension study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the short- and long-term
      efficacy, safety, and tolerability of ziprasidone in adolescents with
      schizophrenia. METHODS: Subjects ages 13-17 years with schizophrenia (American
      Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders,
      4th ed. [DSM-IV]) were enrolled in a 6 week, randomized, double-blind, placebo
      controlled multicenter trial (RCT) followed by a 26 week open-label extension
      study (OLE). Subjects were randomized in a 2:1 ratio to flexible-dose oral
      ziprasidone (40-160 mg/day, based on weight) or placebo. Primary end-point was
      change from baseline in Brief Psychiatric Rating Scale-Anchored (BPRS-A) total
      score. Safety assessments included adverse events, vital signs, laboratory
      measures, electrocardiograms, weight and body mass index, and movement disorder
      ratings. RESULTS: Planned interim analysis for the primary end-point in the RCT
      resulted in early termination of both studies because of futility. In the RCT,
      283 subjects received ziprasidone (n=193) or placebo (n=90). In the intent-to
      treat analysis population, the least squares mean (SE) BPRS-A score decrease from
      baseline at week 6 was not significantly different (p=0.15; -14.16 [0.78] for
      ziprasidone and -12.35 [1.05] for placebo). Per-protocol analysis was significant
      (p=0.02). In the OLE, 221 subjects entered the OLE and received ziprasidone for a
      median of 99 days. The mean (SD) change in BPRS-A score from end of RCT to end of
      OLE (last observation carried forward) was -6.9 (8.9). The most common treatment
      emergent adverse events (>= 10%) for all causalities during the RCT were
      somnolence and extrapyramidal disorders, and during OLE was somnolence only. No
      subjects had Fridericia's corrected QT (QTcF) >= 500 ms in the RCT or OLE phases.
      One completed suicide occurred during the OLE phase. For RCT and OLE, no
      clinically significant changes were reported in metabolic indices and laboratory
      measures. CONCLUSIONS: Ziprasidone failed to separate from placebo in treatment
      of schizophrenia in adolescents. Ziprasidone was generally well tolerated with an
      overall neutral weight and metabolic profile. CLINICAL TRIALS REGISTRY:
      NCT00257192 and NCT00265382 at ClinicalTrials.gov .

PMID- 24111985
TI  - An examination of the factors affecting people's participation in future health
      examinations based on community health exam interventions.
AB  - Community-based intervention health examinations were implemented at a health
      care facility to comply with the government's primary health care promotion
      policy. The theory of planned behavior model was applied to examine the effect
      that community-based health examinations had on people's health concepts
      regarding seeking future health examinations. The research participants were
      individuals who had received a health examination provided at two branches of a
      hospital in central Taiwan in 2012. The hospital's two branches held a total of
      14 free community-based health examination sessions. The hospital provided health
      examination equipment and staff to perform health examinations during public
      holidays. We conducted an exploratory questionnaire survey to collect data and
      implemented cross-sectional research based on anonymous self-ratings to examine
      the public's intention to receive future community-based or hospital-based health
      examinations. Including of 807 valid questionnaires, accounting for 89.4% of the
      total number of questionnaires distributed. The correlation coefficients of the
      second-order structural model indicate that attitudes positively predict
      behavioral intentions (gamma = .66, p < .05), and subjective norms also
      positively predict behavioral intentions (gamma = .66, p < .01). By contrast,
      perceived behavioral control has no significant relationship with behavioral
      intentions (gamma = -.71, p > .05). The results of the first-order structural
      model indicated that the second-order constructs had a high explanatory power for
      the first-order constructs. People's health concepts regarding health
      examinations and their desire to continue receiving health examinations must be
      considered when promoting health examinations in the community. Regarding
      hospital management and the government's implementation of primary health care,
      health examination services should address people's medical needs to increase
      coverage and participation rates and reduce the waste of medical resources.

PMID- 24111984
TI  - The secretogranin II gene is a signal integrator of glutamate and dopamine
      inputs.
AB  - Cooperative gene regulation by different neurotransmitters likely underlies the
      long-term forms of associative learning and memory, but this mechanism largely
      remains to be elucidated. Following cDNA microarray analysis for genes regulated
      by Ca(2+) or cAMP, we found that the secretogranin II gene (Scg2) was
      cooperatively activated by glutamate and dopamine in primary cultured mouse
      hippocampal neurons. The Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid acetoxymethyl ester (BAPTA-AM) and the mitogen-activated protein
      kinase (MAPK) kinase (MEK) inhibitor PD98059 prevented Scg2 activation by
      glutamate or dopamine; thus, the Ca(2+) /MEK pathway is predicted to include a
      convergence point(s) of glutamatergic and dopaminergic signaling. Unexpectedly,
      the protein kinase A inhibitor KT5720 enhanced Scg2 activation by dopamine. The
      protein-synthesis inhibitor cycloheximide also enhanced Scg2 activation, and the
      proteasome inhibitor ZLLLH diminished the KT5720-mediated augmentation of Scg2
      activation. These results are concordant with the notion that dopaminergic input
      leads to accumulation of a KT5720-sensitive transcriptional repressor, which is
      short-lived because of rapid degradation by proteasomes. This repression pathway
      may effectively limit the time window permissive to Scg2 activation by in-phase
      glutamate and dopamine inputs via the Ca(2+) /MEK pathway. We propose that the
      regulatory system of Scg2 expression is equipped with machinery that is refined
      for the signal integration of in-phase synaptic inputs. We proposed hypothetical
      mechanism for the regulation of the secretogranin II gene as a signal integrator
      of glutamate and dopamine inputs. Glutamate or dopamine activates the Ca(2+)
      /MEK/ERK pathway, which thus contributes to the signal integration. Concurrently,
      activation of the PKA inhibitor KT5720-sensitive pathway by dopamine leads to
      accumulation of the repressor protein X that is otherwise susceptible to
      proteasome degradation. This repression system may determine the time window
      permissive to the cooperative activation by in-phase glutamate and dopamine
      inputs.

PMID- 24111986
TI  - Mevalonolactone: an inhibitor of Staphylococcus epidermidis adherence and biofilm
      formation.
AB  - Staphylococcus epidermidis, a commensal microorganism at the human skin and
      mucosae, is nowadays considered an important opportunistic pathogen related to
      nosocomial infections on indwelling medical devices due biofilm formation.
      Bacterial biofilms are the worst aspect in the treatment of infections and now
      efforts have been made in the search for new molecular entities to overcome this
      situation. In this work, a compound isolated from marine associated fungi was
      capable to interfere with the adherence and biofilm formation of S. epidermidis.
      This compound, identified as mevalonolactone, showed significant inhibition of S.
      epidermidis ATCC 35984 biofilm formation, without antibacterial activity,
      evaluated by crystal violet assay, turbidimetric assay and scanning electron
      microscopy. When assayed against 12 clinical isolates of S. epidermidis, this
      compound exhibited both biofilm inhibition and antimicrobial activity, but no
      activity against gram-negative bacteria was observed. Therefore, when this
      constitutive molecule is added in the antibiofilm and antibacterial assays, it
      might act as an important agent against this pathogen, contributing to the
      arsenal of antibiofilm compounds. 

PMID- 24111987
TI  - The cognitive structure of time estimation impairments in adults with attention
      deficit hyperactivity disorder.
AB  - We compared the performance of 15 adults with attention deficit hyperactivity
      disorder (ADHD) and a group of 16 control adults on a temporal bisection task in
      auditory and visual modalities. The point of subjective equality (PSE) and the
      difference limen (DL) were computed to analyse performance. The main findings
      were that (a) individuals with ADHD overestimated the duration of both the
      auditory and visual stimuli in comparison to the control group, as evidenced by a
      shift in their mean PSE; (b) individuals with ADHD also showed less precision in
      their estimates than did the control group as evidenced by flatter psychometric
      functions; and (c) the degrees of overestimation and imprecision in subjects with
      ADHD were comparable across modalities. These results, discussed in the framework
      of the pacemaker-counter clock model of time estimation, suggest that temporal
      difficulties encountered by ADHD patients might be explained both by an alertness
      effect at the level of the switch that directs pulses into the accumulator and
      also by distortions of durations stored in reference memory. 

PMID- 24111988
TI  - A competitive chemical-proteomic platform to identify zinc-binding cysteines.
AB  - Zinc ions (Zn(2+)) play vital catalytic, structural, and regulatory roles in
      protein function and are commonly chelated to cysteine residues within the
      protein framework. Current methods to identify Zn(2+)-binding cysteines rely on
      computational studies based on known Zn(2+)-chelating motifs, as well as high
      resolution structural data. These available approaches preclude the global
      identification of putative Zn(2+)-chelating cysteines, particularly on poorly
      characterized proteins in the proteome. Herein, we describe an experimental
      platform that identifies metal-binding cysteines on the basis of their reduced
      nucleophilicity upon treatment with metal ions. As validation of our platform, we
      utilize a peptide-based cysteine-reactive probe to show that the known Zn(2+)
      chelating cysteine in sorbitol dehydrogenase (SORD) demonstrates an expected loss
      in nucleophilicity in the presence of Zn(2+) ions and a gain in nucleophilicity
      upon treatment with a Zn(2+) chelator. We also identified the active-site
      cysteine in glutathione S-transferase omega-1 (GSTO1) as a potential Zn(2+)
      chelation site, albeit with lower metal affinity relative to SORD. Treatment of
      recombinant GSTO1 with Zn(2+) ions results in a dose-dependent decrease in GSTO1
      activity. Furthermore, we apply a promiscuous cysteine-reactive probe to globally
      identify putative Zn(2+)-binding cysteines across ~900 cysteines in the human
      proteome. This proteomic study identified several well-characterized Zn(2+)
      binding proteins, as well as numerous uncharacterized proteins from functionally
      distinct classes. This platform is highly versatile and provides an experimental
      tool that complements existing computational and structural methods to identify
      metal-binding cysteine residues. 

PMID- 24111989
TI  - Pregnancy losses in women with Type 1 or Type 2 diabetes in the UK: an
      investigation using primary care records.
AB  - AIM: This study aims to investigate pregnancy losses in women with Type 1 or Type
      2 diabetes and compare this with the general population. METHODS: Pregnancies
      ending between 1993 and 2006 in those with Type 1 or Type 2 diabetes were
      identified on the General Practice Research Database. Pregnancy losses were
      identified from medical records and the cohort described by their characteristics
      and prescribing for diabetes. RESULTS: Of 2001 pregnancies identified in women
      with Type 1 diabetes, 678 ended in a pregnancy loss: 19.6% were spontaneous, 9.6%
      were induced and 4.3% were losses for unknown reasons. In women with Type 2
      diabetes, there were 240 losses in 669 pregnancies: 21.1% were spontaneous, 10.3%
      induced and 4.0% were losses for unknown reasons. The proportion of spontaneous
      losses in women with diabetes was higher than in the general population (13.2%).
      Women with Type 1 diabetes treated with human and analogue insulins were 60% more
      likely to have a delivery than a loss (odds ratio 1.6, 95% CI 1.18-2.18) compared
      with human insulin treatment alone, although numbers were small. CONCLUSION: We
      found that the proportions of spontaneous losses in women with Type 1 or Type 2
      diabetes were similar at approximately 20%, which is higher than in the general
      population and also higher than previous studies have reported. While much
      emphasis has been placed on pre-conception care for women with Type 1 diabetes,
      the same is now needed for those with Type 2 diabetes, given the similarity in
      outcomes and increasing prevalence of this condition.

PMID- 24111990
TI  - Temperature affects leaf litter decomposition in low-order forest streams: field
      and microcosm approaches.
AB  - Despite predicted global warming, the temperature effects on headwater stream
      functioning are poorly understood. We studied these effects on microbial-mediated
      leaf decomposition and the performance of associated aquatic hyphomycete
      assemblages. Alder leaves were incubated in three streams differing in winter
      water temperature. Simultaneously, in laboratory, leaf discs conditioned in these
      streams were incubated at 5, 10 and 15  degrees C. We determined mass loss, leaf
      N and sporulation rate and diversity of aquatic hyphomycete communities. In the
      field, decomposition rate correlated positively with temperature. Decomposition
      rate and leaf N presented a positive trend with dissolved nutrients, suggesting
      that temperature was not the only factor determining the process velocity. Under
      controlled conditions, it was confirmed that decomposition rate and leaf N were
      positively correlated with temperature, leaves from the coldest stream responding
      most clearly. Sporulation rate correlated positively with temperature after 9
      days of incubation, but negatively after 18 and 27 days. Temperature rise
      affected negatively the sporulating fungi richness and diversity only in the
      material from the coldest stream. Our results suggest that temperature is an
      important factor determining leaf processing and aquatic hyphomycete assemblages
      and that composition and activity of fungal communities adapted to cold
      environments could be more affected by temperature rises. Highlight: Leaf
      decomposition rate and associated fungal communities respond to temperature
      shifts in headwater streams.

PMID- 24111991
TI  - Radical cyclizations of cyclic ene sulfonamides occur with beta-elimination of
      sulfonyl radicals to form polycyclic imines.
AB  - Radical cyclizations of cyclic ene sulfonamides provide stable bicyclic and
      tricyclic aldimines and ketimines in good yields. Depending on the structure of
      the precursor, the cyclizations occur to provide fused and spirocyclic imines
      with five-, six-, and seven-membered rings. The initial radical cyclization
      produces an alpha-sulfonamidoyl radical that undergoes elimination to form the
      imine and a phenylsulfonyl radical. In a related method, 3,4-dihydroquinolines
      can also be produced by radical translocation reactions of N-(2
      iodophenylsulfonyl)tetrahydroiso-quinolines. In either case, very stable
      sulfonamides are cleaved to form imines (rather than amines) under mild reductive
      conditions.

PMID- 24111993
TI  - Age-related changes in spreading activation during infancy.
AB  - The concept of spreading activation describes how retrieval of one memory cues
      retrieval of other memories that are associated with it. This study explored
      spreading activation in 6-, 12-, and 18-month-old infants. Infants (n = 144)
      learned two tasks within the same experimental session; one task, deferred
      imitation (DI), is typically remembered longer than the other task, visual
      recognition memory (VRM). At all ages, retrieval of the DI memory facilitated
      retrieval of the VRM memory, but the conditions under which this spreading
      activation occurred changed as a function of age. The implications of these
      findings are discussed in relation to the development of mnemonic networks during
      infancy and the value of studying infants for our understanding of memory more
      generally.

PMID- 24111992
TI  - Surfactant protein D (SP-D) deficiency is attenuated in humanised mice expressing
      the Met(11)Thr short nucleotide polymorphism of SP-D: implications for surfactant
      metabolism in the lung.
AB  - Surfactant protein D (SP-D) is part of the innate immune system involved in lung
      homeostasis. SP-D knockout mice show accumulations of foamy alveolar macrophages,
      alveolar lipoproteinosis and pulmonary emphysema. Three single nucleotide
      polymorphisms (SNPs) have been described in the coding sequence of the human SP-D
      gene SFTPD. Clinical studies showed that the SNP SFTPD with a nucleotide change
      from A to C resulting in a Met to Thr substitution at position 11 in the protein
      (Met(11)Thr), is relevant. This study set out to create a humanised mouse model
      of the Met(11)Thr SNP. Transgenic mice lines expressing either Met(11) or Thr(11)
      SP-D under the control of the ubiquitously expressed pROSA26 promoter in C57Bl/6
      SP-D deficient mice (DKO) was created. Both Met(11) (142 +/- 52 ng mL(-1) ) and
      Thr(11) (228 +/- 76 ng mL(-1) ) mice lines expressed human SP-D at almost similar
      levels. According to the literature this was within the range of SP-D levels
      found in wildtype (WT) mice (253 +/- 22 ng mL(-1) ). Met(11) or Thr(11) SP-D in
      serum from transgenic mice bound maltose in a calcium-dependent manner, and
      binding was inhibited in the presence of EDTA or maltose. Bronchoalveolar lavage
      showed for both transgenic mice lines complementation of the DKO phenotype by
      restoring cell counts, phospholipid levels and protein content back to WT levels.
      Cytospins of BAL pellet cells showed a resemblance to WT but both mice lines
      showed some foamy alveolar macrophages. The stereological analysis showed for
      none of the mice lines a complete abrogation of emphysematous alterations.
      However, both Met(11) and Thr(11) mice lines were partially reverted back to a WT
      phenotype when compared with DKO mice, indicating important effects on surfactant
      metabolism in vivo. 

PMID- 24111994
TI  - Honour-related threats and human rights: a qualitative study of Swedish
      healthcare providers' attitudes towards young women requesting a virginity
      certificate or hymen reconstruction.
AB  - OBJECTIVES: To investigate the preferred actions of healthcare staff, as well as
      their reasoning and attitudes about young females' requests for a virginity
      certificate or hymen restoration. METHOD: A qualitative study, consisting of semi
      structured interviews of healthcare providers from different parts of Sweden and
      from different medical specialties and professions, who had experience of women
      who asked for a virginity certificate or a hymen repair. RESULTS: Using content
      analysis, ten themes emerged regarding healthcare personnel's attitudes and
      reasoning about young female patients and their requests for demonstration of
      virginity. The themes logically were categorised as values, beliefs, and cultural
      affiliation. CONCLUSIONS: Responders had a more pragmatic and permissive view
      than the restrictive, official Swedish policy opposing hymenoplasties within the
      public healthcare system. There were degrees of willingness to accommodate such
      requests, due, for example, to different moral beliefs and medical concerns.
      Responders expressed frustration over the difficulty of following up patients, a
      situation likely due to the restrictive policy. The patient-centred approach
      adopted by a Dutch team of health professionals would probably better enable
      quality assurance.

PMID- 24111996
TI  - The ethics of testing in children.

PMID- 24111995
TI  - The dependence of the ice-albedo feedback on atmospheric properties.
AB  - Ice-albedo feedback is a potentially important destabilizing effect for the
      climate of terrestrial planets. It is based on the positive feedback between
      decreasing surface temperatures, an increase of snow and ice cover, and an
      associated increase in planetary albedo, which then further decreases surface
      temperature. A recent study shows that for M stars, the strength of the ice
      albedo feedback is reduced due to the strong spectral dependence of stellar
      radiation and snow/ice albedos; that is, M stars primarily emit in the near IR,
      where the snow and ice albedo is low, and less in the visible, where the snow/ice
      albedo is high. This study investigates the influence of the atmosphere (in terms
      of surface pressure and atmospheric composition) on this feedback, since an
      atmosphere was neglected in previous studies. A plane-parallel radiative transfer
      model was used for the calculation of planetary albedos. We varied CO2 partial
      pressures as well as the H2O, CH4, and O3 content in the atmosphere for planets
      orbiting Sun-like and M type stars. Results suggest that, for planets around M
      stars, the ice-albedo effect is significantly reduced, compared to planets around
      Sun-like stars. Including the effects of an atmosphere further suppresses the
      sensitivity to the ice-albedo effect. Atmospheric key properties such as surface
      pressure, but also the abundance of radiative trace gases, can considerably
      change the strength of the ice-albedo feedback. For dense CO2 atmospheres of the
      order of a few to tens of bar, atmospheric rather than surface properties begin
      to dominate the planetary radiation budget. At high CO2 pressures, the ice-albedo
      feedback is strongly reduced for planets around M stars. The presence of trace
      amounts of H2O and CH4 in the atmosphere also weakens the ice-albedo effect for
      both stellar types considered. For planets around Sun-like stars, O3 could also
      lead to a very strong decrease of the ice-albedo feedback at high CO2 pressures.

PMID- 24111999
TI  - Ombudsman warns of deaths linked to poor sepsis treatment.

PMID- 24112003
TI  - Why girls fall into gang culture.

PMID- 24112004
TI  - Children with epilepsy are at risk from schools' lack of care plans.

PMID- 24112010
TI  - Quality of newborn screening information needs to improve.

PMID- 24112013
TI  - Starting out - One year on.

PMID- 24112018
TI  - Why we still need to be vigilant about polio here and abroad.

PMID- 24112019
TI  - Student voice - Tough topic.

PMID- 24112020
TI  - Parental decisions on children participating in research.
AB  - AIM: To observe and report rates of, and reasons for, parents' refusal to consent
      to the participation of their children in appropriate clinical research. METHODS:
      The parents of children admitted to hospital with a diagnosis of pneumonia or of
      empyema were asked for informed consent to research involving blood, urine and
      nasopharyngeal secretion samples from their child. Circumstances and numbers of
      agreements and refusals were compared and underlying reasons suggested. RESULTS:
      Of 144 consent requests, ten were refused, which appeared to be linked to: not
      wanting the child to undergo further tests, lack of interest in participating in
      studies, research possibly delaying discharge, and anxiety regarding written
      consent and the length of information sheets. CONCLUSIONS: Severity of the
      child's illness appeared to determine the parent's decision. Involvement and
      assistance of non-research nursing and medical staff and previous introductions
      to the researchers are helpful. The timing and setting for the consent process
      should be selected carefully. Adequate, accessible study information for parents
      and children contributes to successful recruitment of participants.

PMID- 24112021
TI  - Messy boundaries: younger students' experiences of nursing young people in
      hospital.
AB  - AIMS: To explore the experience of younger students of children's nursing when
      required to care for clients of similar age in hospital, and their concerns in
      relation to professional boundaries. METHODS: A phenomenological study was
      undertaken as a requirement of the doctorate in education programme. Individual
      unstructured interviews were conducted with 11 students under 20 years of age,
      and nine of their young clients. FINDINGS: The students described the
      difficulties of trying to balance being a friend to the young people to gain
      trust, with maintaining a professional relationship. CONCLUSION: Students of
      children's nursing should be encouraged to relate to their clients of similar age
      in a professional way that inspires trust and therapeutic engagement. For this
      the students need the support and guidance of their tutors, mentors and peers.

PMID- 24112022
TI  - Educating children's nurses for communicating bad news.
AB  - Some parents are unhappy with the way news is broken to them. This article seeks
      to educate and inform the reflective practitioner on a series of communication
      strategies to enhance their skills. This is important because the way news is
      disclosed can affect the way news is accepted and the level of support the family
      will require. The importance of clarity, honesty and empathy is emphasised. 

PMID- 24112023
TI  - Striving to excel.

PMID- 24112024
TI  - Fragment-based identification of a locus in the Sec7 domain of Arno for the
      design of protein-protein interaction inhibitors.
AB  - By virtual screening using a fragment-based drug design (FBDD) approach, 33
      fragments were selected within small pockets around interaction hot spots on the
      Sec7 surface of the nucleotide exchange factor Arno, and then their ability to
      interfere with the Arno-catalyzed nucleotide exchange on the G-protein Arf1 was
      evaluated. By use of SPR, NMR, and fluorescence assays, the direct binding of
      three of the identified fragments to Arno Sec7 domain was demonstrated and the
      promiscuous aggregate behavior evaluated. Then the binding mode of one fragment
      and of a more active analogue was solved by X-ray crystallography. This
      highlighted the role of stable and transient pockets at the Sec7 domain surface
      in the discovery and binding of interfering compounds. These results provide
      structural information on how small organic compounds can interfere with the Arf1
      Arno Sec7 domain interaction and may guide the rational drug design of
      competitive inhibitors of Arno enzymatic activity. 

PMID- 24112025
TI  - Formation and infrared spectroscopic characterization of three oxygen-rich BiO4
      isomers in solid argon.
AB  - The reactions of bismuth atoms and O2 have been investigated using matrix
      isolation infrared spectroscopy and density functional theory calculations. The
      ground state bismuth atoms react with dioxygen to form the BiOO and Bi(O2)2
      complexes spontaneously on annealing. The BiOO molecule is characterized to be an
      end-on bonded superoxide complex, while the Bi(O2)2 molecule is characterized to
      be a superoxo bismuth peroxide complex, [Bi(3+)(O2(-))(O2(2-))]. Under UV-visible
      light irradiation, the Bi(O2)2 complex rearranges to the more stable OBiOOO
      isomer, an end-on bonded bismuth monoxide-ozonide complex. The end-on-bonded
      OBiOOO complex further rearranges to a more stable side-on bonded OBiO3 isomer
      upon sample annealing. In addition, the bent bismuth dioxide anion is also formed
      and assigned. 

PMID- 24112026
TI  - Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab
      (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple
      myeloma.
AB  - CD74, expressed in multiple myeloma (MM), was evaluated as a target for
      immunotherapy with milatuzumab (a humanized anti-CD74 antibody). In a multicentre
      dose escalation study, 25 patients with advanced MM received milatuzumab doses of
      1.5 (N = 8), 4.0 (N = 9), 8.0 (N = 4) or 16.0 mg/kg (N = 4) administered twice
      weekly x 4. They had a median of 5 prior treatments (17 post >= 1 stem cell
      transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally
      short-lived responses to last treatment (median 4.0 months). After increasing
      prophylactic medications and slowing administration, infusions were well
      tolerated (National Cancer Institute-Common Terminology Criteria v3 toxicity
      Grades 1-2) with no dose-limiting toxicity at higher doses. Only one patient
      developed borderline positive human anti-milatuzumab antibody titres of uncertain
      clinical significance. Although milatuzumab was rapidly cleared from circulation
      with little serum accumulation and low trough levels, B-cell levels were
      moderately decreased with treatment (median decrease, 34%). There were no
      objective responses by European Group for Blood and Marrow Transplantation
      criteria, but 5 of 19 patients (26%) who completed treatment in this heavily
      pretreated and generally refractory group had stable disease for >= 3 months post
      treatment (one continuing for 17 months). Disease stabilization and evidence of
      pharmacodynamic activity support further development for use in combination with
      other agents or as a drug conjugate.

PMID- 24112027
TI  - Biodegradation and cometabolic modeling of selected beta blockers during ammonia
      oxidation.
AB  - Accurate prediction of pharmaceutical concentrations in wastewater effluents
      requires that the specific biochemical processes responsible for pharmaceutical
      biodegradation be elucidated and integrated within any modeling framework. The
      fate of three selected beta blockers-atenolol, metoprolol, and sotalol-was
      examined during nitrification using batch experiments to develop and evaluate a
      new cometabolic process-based (CPB) model. CPB model parameters describe
      biotransformation during and after ammonia oxidation for specific biomass
      populations and are designed to be integrated within the Activated Sludge Models
      framework. Metoprolol and sotalol were not biodegraded by the nitrification
      enrichment culture employed herein. Biodegradation of atenolol was observed and
      linked to the activity of ammonia-oxidizing bacteria (AOB) and heterotrophs but
      not nitrite-oxidizing bacteria. Results suggest that the role of AOB in atenolol
      degradation may be disproportionately more significant than is otherwise
      suggested by their lower relative abundance in typical biological treatment
      processes. Atenolol was observed to competitively inhibit AOB growth in our
      experiments, though model simulations suggest inhibition is most relevant at
      atenolol concentrations greater than approximately 200 ng.L(-1). CPB model
      parameters were found to be relatively insensitive to biokinetic parameter
      selection suggesting the model approach may hold utility for describing
      pharmaceutical biodegradation during biological wastewater treatment. 

PMID- 24112028
TI  - Polyamines reprogram oxidative and nitrosative status and the proteome of citrus
      plants exposed to salinity stress.
AB  - The interplay among polyamines (PAs) and reactive oxygen and nitrogen species
      (RNS and ROS) is emerging as a key issue in plant responses to salinity. To
      address this question, we analysed the impact of exogenous PAs [putrescine (Put),
      spermidine (Spd) and spermine (Spm)] on the oxidative and nitrosative status in
      citrus plants exposed to salinity. PAs partially reversed the NaCl-induced
      phenotypic and physiological disturbances. The expression of PA biosynthesis
      (ADC, SAMDC, SPDS and SPMS) and catabolism (DAO and PAO) genes was systematically
      up-regulated by PAs. In addition, PAs altered the oxidative status in salt
      stressed plants as inferred by changes in ROS production and redox status
      accompanied by regulation of transcript expression and activities of various
      antioxidant enzymes. Furthermore, NaCl-induced up-regulation of NO-associated
      genes, such as NR, NADde, NOS-like and AOX, along with S-nitrosoglutathione
      reductase and nitrate reductase activities, was partially restored by PAs.
      Protein carbonylation and tyrosine nitration are depressed by specific PAs
      whereas protein S-nitrosylation was elicited by all PAs. Furthermore, we
      identified 271 S-nitrosylated proteins that were commonly or preferentially
      targeted by salinity and individual PAs. This work helps improve our knowledge on
      the plant's response to environmental challenge.

PMID- 24112030
TI  - Injection site reactions of adalimumab spreading on the trunk in a psoriatic
      arthritis patient.

PMID- 24112029
TI  - Correlation between self-reported and clinically based diagnoses of bruxism in
      temporomandibular disorders patients.
AB  - The present investigation was performed in a population of patients with
      temporomandibular disorders (TMD), and it was designed to assess the correlation
      between self-reported questionnaire-based bruxism diagnosis and a diagnosis based
      on history taking plus clinical examination. One-hundred-fifty-nine patients with
      TMD underwent an assessment including a questionnaire investigating five bruxism
      related items (i.e. sleep grinding, sleep grinding referral by bed partner, sleep
      clenching, awake clenching, awake grinding) and an interview (i.e. oral history
      taking with specific focus on bruxism habits) plus a clinical examination to
      evaluate bruxism signs and symptoms. The correlation between findings of the
      questionnaire, viz., patients' report, and findings of the interview/oral history
      taking plus clinical examination, viz., clinicians' diagnosis, was assessed by
      means of phi coefficient. The highest correlations were achieved for the sleep
      grinding referral item (phi = 0.932) and for the awake clenching item (phi =
      0.811), whilst lower correlation values were found for the other items (phi
      values ranging from 0.363 to 0.641). The percentage of disagreement between the
      two diagnostic approaches ranged between 1.8% and 18.2%. Within the limits of the
      present investigation, it can be suggested that a strong positive correlation
      between a self-reported and a clinically based approach to bruxism diagnosis can
      be achieved as for awake clenching, whilst lower levels of correlation were
      detected for sleep-time activities. 

PMID- 24112031
TI  - Activation of organum vasculosum of lamina terminalis, median preoptic nucleus,
      and medial preoptic area in anticipation of nursing in rabbit pups.
AB  - Rhythmic feeding in rabbit pups is a natural model to study food entrainment
      because, similar to rodents under a schedule of food restriction, these animals
      show food-anticipatory activity (FAA) prior to daily nursing. In rodents, several
      brain systems, including the orexinergic system, shift their activity to the
      restricted feeding schedule, and remain active when subjects are hungry. As the
      lamina terminalis and regions of the preoptic area participate in the control of
      behavioral arousal, it was hypothesized that these brain regions are also
      activated during FAA. Thus, the effects of daily milk ingestion on FOS protein
      expression in the organum vasculosum of lamina terminalis (OVLT), median preoptic
      nucleus (MnPO), and medial preoptic area (MPOA) were examined using
      immunohistochemistry before and after scheduled time of nursing in nursed and
      fasted subjects. Additionally, FOS expression was explored in orexin (ORX) cells
      in the lateral hypothalamic area and in the supraoptic nucleus (SON) because of
      their involvement in arousal and fluid ingestion, respectively. Pups were
      entrained by daily nursing, as indicated by a significant increase in locomotor
      behavior before scheduled time of nursing in both nursed and fasted subjects. FOS
      was significantly higher in the OVLT, MnPO, and MPOA at the time of nursing, and
      decreased 8 h later in nursed pups. In fasted subjects, this effect persisted in
      the OVLT, whereas in the MnPO and MPOA, values did not drop at 8 h later, but
      remained at the same level or higher than those at the time of scheduled nursing.
      In addition, FOS was significantly higher in ORX cells during FAA in nursed pups
      in comparison with 8 h later, but in fasted subjects it remained high during most
      fasting time points. Additionally, OVLT, SON, and ORX cells were activated 1.5 h
      after nursing. We conclude that the OVLT, MnPO, and MPOA, but not SON, may
      participate in FAA, as they show activation before suckling of periodic milk
      ingestion, and that sustained activation of the OVLT, MnPO, and MPOA by fasting
      may contribute to the high arousal state associated with food deprivation. In
      agreement with this, ORX cells also remain active after expected nursing, which
      is consistent with reports in other species.

PMID- 24112032
TI  - Synthesis, characterization, photophysics and photochemistry of pyrylogen
      electron transfer sensitizers.
AB  - A series of new dicationic sensitizers that are hybrids of pyrylium salts and
      viologens has been synthesized. The electrochemical and photophysical properties
      of these "pyrylogen" sensitizers are reported in sufficient detail to allow
      rationale design of new photoinduced electron transfer reactions. The range of
      their reduction potentials (+0.37-+0.05 V vs SCE) coupled with their range of
      singlet (48-63 kcal mol(-1)) and triplet (48-57 kcal mol(-1)) energies
      demonstrate that they are potent oxidizing agents in both their singlet and
      triplet excited states, thermodynamically capable of oxidizing substrates with
      oxidation potentials as high as 3.1 eV. The pyrylogens are synthesized in three
      steps from readily available starting materials in modest overall 11.4-22.3%
      yields. These sensitizers have the added advantages that: (1) their radical
      cations do not react on the CV timescale with oxygen bypassing the need to run
      reactions under nitrogen or argon and (2) have long wavelength absorptions
      between 413 and 523 nm well out of the range where competitive absorbance by most
      substrates would cause a problem. These new sensitizers do react with water
      requiring special precautions to operate in a dry reaction environment.

PMID- 24112033
TI  - Do prolonged primary transport times for traumatic brain injury patients result
      in deteriorating physiology? A cohort study.
AB  - BACKGROUND: Recent interest has focused on reorganizing emergency medical
      services (EMS) for traumatic brain injury (TBI) patients, with bypass of
      nonspecialist hospitals and direct transportation to distant neuroscience
      centers. Although this could expedite neurosurgery and neurocritical care,
      deteriorating physiology could be deleterious. METHODS: We performed a
      multicenter cohort study examining adult patients with significant TBI enrolled
      in the English National Trauma Registry. The distributions and correlation of
      first recorded prehospital and emergency department (ED) vital signs were
      compared, and the effect of time on changes in vital signs was examined in
      bivariate and multivariate analyses. RESULTS: A total of 7149 eligible patients
      were studied. No clinically significant differences were apparent between
      distributions of prehospital and ED vital signs. Moderate linear correlation was
      observed for field and ED pulse rate (r(2) = 0.34) and GCS values (Spearman's rho
      = 0.76), with weak correlation apparent for systolic blood pressure (r(2) = 0.28)
      and respiratory rate (r(2) = 0.28). Eight percent of cases' vital signs
      deteriorated in the prehospital interval; however, odds of deterioration in vital
      sign status did not vary significantly with duration of EMS interval. CONCLUSION:
      The similarity between prehospital and ED vital signs, and lack of association
      between EMS interval and physiological deterioration, may support a strategy of
      direct transportation of TBI cases to specialist centers. Further research is
      necessary to identify patients at risk from deterioration during bypass and to
      investigate effects on mortality.

PMID- 24112034
TI  - Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2
      gene polymorphisms with essential hypertension in the population of Odisha,
      India.
AB  - BACKGROUND: Hypertension is a serious health issue worldwide and essential
      hypertension, which includes 90-95% of the cases, is influenced by both genetic
      and environmental factors. Identification of these factors may help in control of
      this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting
      Enzyme (ACE) gene and rs2106809 (C > T) polymorphism in Angiotensin-Converting
      Enzyme 2 (ACE2) gene have been reported to be associated with essential
      hypertension in different populations. AIM: To investigate the association of ACE
      I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the
      population of Odisha, an eastern Indian state. SUBJECTS AND METHODS: A total of
      246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and
      116 females) were enrolled in the study. Detailed anthropometric data, tobacco,
      alcohol and food habits were recorded and 2 ml of venous blood was collected for
      biochemical and genetic analysis. RESULTS: The DD genotype of ACE and TT genotype
      of ACE2 were significantly high among female hypertensives, while T allele of
      ACE2 was linked to male hypertensives. In the male population, alcohol was also
      identified as a potential risk factor. CONCLUSION: Among females, ACE I/D and
      ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and
      alcohol consumption are associated with essential hypertension in the study
      population.

PMID- 24112035
TI  - Molecular community profiling reveals impacts of time, space, and disease status
      on the bacterial community associated with the Caribbean sponge Aplysina
      cauliformis.
AB  - Reports of marine sponge diseases have increased in recent years, but few
      etiologic agents have been identified. Aplysina red band syndrome (ARBS), a
      condition observed in the Caribbean sponge Aplysina cauliformis, is characterized
      by a rust-colored leading margin. Culture-independent methods (terminal
      restriction fragment length polymorphism and clone library analyses) were used to
      assess bacterial communities associated with healthy and ARBS-affected sponges
      from two locations over 2 years. Although the bacterial communities associated
      with healthy and ARBS-affected sponges were significantly different, the sponges
      maintained a core bacterial community across space, time, and health status. Ten
      terminal restriction fragments were shown to change significantly between sponge
      health conditions, with six increasing in abundance with disease and four
      decreasing. The prevalence of the photosymbiont Synechococcus spongiarum
      decreased with ARBS infection, suggesting a functional consequence of disease.
      After cultivating a red-pigmented Leptolyngbya strain from ARBS lesions,
      transmission studies were conducted to determine whether this organism was the
      ARBS pathogen. Despite significantly increased abundance of Leptolyngbya spp. in
      diseased sponges, signs of ARBS were not observed in healthy sponges following 24
      days of contact with the cultured strain. Additional work with this model system
      is needed to increase our understanding of the dynamics of marine diseases.

PMID- 24112036
TI  - Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells
      exposed to methylglyoxal stress.
AB  - Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated
      neuroprotective properties in a range of studies. In an APPswe/PS1DeltaE9 mouse
      model of Alzheimer's disease (AD), we previously found protective effects on
      memory formation, synaptic plasticity, synapse survival and a reduction of
      amyloid synthesis and plaque load in the brain. Here, we analyse the
      neuroprotective properties of the GLP-1 analogue liraglutide in human
      neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the
      first time that cell viability was enhanced by liraglutide (XTT assay) in a dose
      dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced.
      Expression of the pro-survival Mcl1 signaling protein was increased, as was
      activation of cell survival kinases Akt, MEK1/2 and the transcription factor
      p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In
      addition, the membrane potential and the influx of calcium into the cell were
      enhanced by liraglutide. GLP-1 receptor expression was also increased by the
      drug. The results demonstrate a range of growth factor-related cytoprotective
      processes induced by liraglutide, which is currently on the market as a treatment
      for type 2 diabetes (Victoza(r)). It is also tested in clinical trials in
      patients with Alzheimer disease.

PMID- 24112037
TI  - Biodegradable stereocomplex micelles based on dextran-block-polylactide as
      efficient drug deliveries.
AB  - Biodegradable stereocomplex micelles (SCMs) based on amphiphilic dextran-block
      polylactide (Dex-b-PLA) were designed and used for efficient intracellular drug
      deliveries. The Dex-b-PLA copolymers were successfully synthesized by click
      reaction. The structures of the resultant copolymers were verified by (1)H NMR
      and FT-IR spectra. The formation of stable micelles through self-assembly driven
      by the stereocomplexation between enantiomeric l- and d-PLA blocks was
      characterized by transmission electron microscopy (TEM), dynamic laser scattering
      (DLS), and fluorescence techniques. It was interesting to observe that the SCMs
      showed lower critical micelle concentration values (CMCs) because of the
      stereocomplex interaction between PLLA and PDLA. Differential scanning
      calorimetry (DSC) and X-ray diffraction (XRD) analysis provided information on
      the thermal and crystal properties of the copolymers and SCMs. The improved
      stability of SCMs should be attractive for intracellular drug delivery. Thus, a
      model anticancer drug doxorubicin (DOX) was loaded into micelles, and the in
      vitro drug release in was also studied. The release kinetics of DOX showed DOX
      loaded SCMs exhibited slower DOX release. Confocal laser scanning microscopy
      (CLSM) and flow cytometry studies also showed that the DOX-loaded SCMs exhibited
      a slower drug release behavior. Meanwhile, the MTT assay demonstrated that DOX
      loaded SCMs show lower cellular proliferation inhibition against HepG2. In sum,
      the micelles through self-assembly driven by stereocomplex interaction would have
      great potential to be used as stable delivery vehicles for pharmaceutical and
      biomedical applications. 

PMID- 24112038
TI  - pVHL acts as a downstream target of E2F1 to suppress E2F1 activity.
AB  - The VHL (von Hippel-Lindau) gene is a well-defined tumour suppressor linked to
      hereditary cancer syndromes. Although it is well documented that pVHL (von Hippel
      Lindau protein) mediates HIF (hypoxia-inducible factor)-1/2alpha degradation
      under conditions of normoxia, accounting for a major mechanism of pVHL in tumour
      suppression, it remains elusive whether other HIF-independent functions
      contribute to the pVHL tumour suppressive function. In the present study, we
      found that pVHL is a downstream target of E2F1, which harbours an E2F1-binding
      site in its promoter. Moreover, pVHL binds to E2F1 in vitro and in vivo,
      resulting in inhibition of E2F1 transcriptional activity. Mechanistic studies
      showed that pVHL binding enhances E2F1 deacetylation. Further immunoprecipitation
      assays indicated that the pVHL interaction diminishes P/CAF [p300/CREB (cAMP
      response-element-binding protein)-binding protein-associated factor] and p300
      association with E2F1, but enhances Sirt1 (sirtuin 1) binding to E2F1. In
      addition, upon DNA damage, pVHL is induced. Knockdown of pVHL sensitizes cells to
      DNA-damage-induced apoptosis dependent on E2F1, uncovering a role for pVHL in the
      response to DNA damage. The findings of the present study reveal a novel function
      of pVHL and demonstrate a negative-feedback loop between pVHL and E2F1, which may
      shed new light on the explanation of the role of pVHL in tumour suppression.

PMID- 24112039
TI  - Adolescents and young adults with newly diagnosed Type 2 diabetes demonstrate
      greater carotid intima-media thickness than those with Type 1 diabetes.
AB  - AIM: To compare the carotid intima-media thickness in patients with newly
      diagnosed Type 1 or Type 2 diabetes ranging from 14 to 30 years of age. METHODS:
      Demographic, anthropometric and laboratory data were obtained from 404
      adolescents and young adults (103 subjects with Type 1 diabetes, 94 with Type 2
      diabetes, 153 obese subjects and 54 normal control subjects). Carotid intima
      media thickness was assessed based on Doppler ultrasound examination and compared
      among the four groups. RESULTS: Our data showed significant increases in carotid
      intima-media thickness in subjects with Type 1 diabetes, Type 2 diabetes and
      obese subjects compared with the control subjects, with those in the group with
      Type 2 diabetes demonstrating the greatest change (P < 0.001). Age, BMI,
      percentage of fat, waist-hip ratio and total triglycerides were significantly
      correlated with both common and internal carotid intima-media thickness segments.
      From a stepwise multiple linear regression model, the independent determinants of
      common carotid intima-media thickness were age, BMI, HbA1c and HDL cholesterol
      (adjusted R(2)  = 0.152, P < 0.001). After adjustment for age, sex and HbA1c ,
      the odds ratio for increased carotid intima-media thickness was 1.67 (95% CI 1.19
      2.33, P = 0.003) for obese subjects, 2.38 (95% CI 1.59-9.47, P = 0.001) for
      subjects with Type 1 diabetes and 3.93 (95% CI 1.90-6.07, P = 0001) for subjects
      with Type 2 diabetes compared with the control subjects. CONCLUSIONS: Compared
      with young control subjects, we found significant increases in carotid intima
      media thickness in patients with newly diagnosed Type 1 diabetes and Type 2
      diabetes, with patients with Type 2 diabetes showing greater carotid intima-media
      thickness. Traditional cardiovascular risk factors, such as obesity,
      dyslipidaemia, hypertension and hyperglycaemia, could cause vessel changes even
      in adolescents and young adults.

PMID- 24112040
TI  - A framework for developing objective and measurable recovery criteria for
      threatened and endangered species.
AB  - For species listed under the U.S. Endangered Species Act (ESA), the U.S. Fish and
      Wildlife Service and National Marine Fisheries Service are tasked with writing
      recovery plans that include "objective, measurable criteria" that define when a
      species is no longer at risk of extinction, but neither the act itself nor agency
      guidelines provide an explicit definition of objective, measurable criteria. Past
      reviews of recovery plans, including one published in 2012, show that many
      criteria lack quantitative metrics with clear biological rationale and are not
      meeting the measureable and objective mandate. I reviewed how objective,
      measureable criteria have been defined implicitly and explicitly in peer-reviewed
      literature, the ESA, other U.S. statutes, and legal decisions. Based on a
      synthesis of these sources, I propose the following 6 standards be used as
      minimum requirements for objective, measurable criteria: contain a quantitative
      threshold with calculable units, stipulate a timeframe over which they must be
      met, explicitly define the spatial extent or population to which they apply,
      specify a sampling procedure that includes sample size, specify a statistical
      significance level, and include justification by providing scientific evidence
      that the criteria define a species whose extinction risk has been reduced to the
      desired level. To meet these 6 standards, I suggest that recovery plans be
      explicitly guided by and organized around a population viability modeling
      framework even if data or agency resources are too limited to complete a
      viability model. When data and resources are available, recovery criteria can be
      developed from the population viability model results, but when data and
      resources are insufficient for model implementation, extinction risk thresholds
      can be used as criteria. A recovery-planning approach centered on viability
      modeling will also yield appropriately focused data-acquisition and monitoring
      plans and will facilitate a seamless transition from recovery planning to
      delisting.

PMID- 24112042
TI  - Yolk-shell structure of polyaniline-coated sulfur for lithium-sulfur batteries.
AB  - Lithium-sulfur batteries have attracted much attention in recent years due to
      their high theoretical capacity of 1672 mAh g(-1) and low cost. However, a rapid
      capacity fade is normally observed, attributed mainly to polysulfide dissolution
      and volume expansion. Although many strategies have been reported to prolong the
      cyclability, the high cost and complex preparation processes still hinder their
      practical application. Here, we report the synthesis of a polyaniline-sulfur yolk
      shell nanocomposite through a heating vulcanization of a polyaniline-sulfur core
      shell structure. We observed that this heating treatment was much more effective
      than chemical leaching to prepare uniform yolk-shell structures. Compared with
      its sulfur-polyaniline core-shell counterparts, the yolk-shell nanostructures
      delivered much improved cyclability owing to the presence of internal void space
      inside the polymer shell to accommodate the volume expansion of sulfur during
      lithiation. The yolk-shell material exhibited a stable capacity of 765 mAh g(-1)
      at 0.2 C after 200 cycles, representing a promising future for industrial scale
      Li-S batteries.

PMID- 24112041
TI  - Deconstructing building blocks: preschoolers' spatial assembly performance
      relates to early mathematical skills.
AB  - This study focuses on three main goals: First, 3-year-olds' spatial assembly
      skills are probed using interlocking block constructions (N = 102). A detailed
      scoring scheme provides insight into early spatial processing and offers
      information beyond a basic accuracy score. Second, the relation of spatial
      assembly to early mathematical skills was evaluated. Spatial skill independently
      predicted a significant amount of the variability in concurrent mathematical
      performance. Finally, the relation between spatial assembly skill and
      socioeconomic status (SES), gender, and parent-reported spatial language was
      examined. While children's performance did not differ by gender, lower SES
      children were already lagging behind higher SES children in block assembly.
      Furthermore, lower SES parents reported using significantly fewer spatial words
      with their children.

PMID- 24112043
TI  - The cortical excitability profile of temporal lobe epilepsy.
AB  - PURPOSE: Transcranial magnetic stimulation (TMS) was used to characterize
      measurable changes of cortical excitability in patients who were undergoing
      medical and surgical management of temporal lobe epilepsy (TLE) to investigate
      whether these alterations depended on timing of achieving seizure control
      throughout the course of illness and method of management. METHODS: Eighty-five
      patients with TLE divided into (1) drug naive-new onset, (2) early medically
      refractor, and (3) late medically refractory, (4) early seizure-free on
      antiepileptic drugs, and (5) late seizure-free on antiepileptic drugs, (6)
      postoperative refractory, and (7) postoperative seizure-free groups were studied.
      Motor threshold (MT) and paired-pulse TMS at short (2, 5, 10, and 15 msec) and
      long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were
      compared to those of 20 controls. KEY FINDINGS: A significant interhemispheric
      difference was observed early at onset prior to starting medication, with higher
      cortical excitability in the hemisphere ipsilateral to the seizure focus, whereas
      the unaffected hemisphere was normal. After that, cortical excitability was
      higher in both hemispheres in the refractory groups (medical and postoperative)
      compared to the seizure-free and drug-naive groups (p < 0.05). This effect was
      most prominent at the long ISIs. SIGNIFICANCE: Changes in cortical excitability
      seen in patients with TLE are influenced by the course of the disease. The
      alterations that occur due to epilepsy are closely related to course of illness
      and degree/timing of seizure control. Successful management leads to resolution
      of this cortical hyperexcitability in a similar fashion regardless of method:
      medication (intact generator, but modulated by drugs) or surgery (generator
      removed).

PMID- 24112044
TI  - Committed mast cell progenitors in mouse blood differ in maturity between Th1 and
      Th2 strains.
AB  - Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral
      tissues where they mature. Although the existence of committed MCp in adult mouse
      and human blood has been postulated, they have never been found. We have isolated
      a rare population of cells in adult mouse blood, committed to the mast cell
      lineage. These were identified as lineage- c-kit(hi) ST2+ integrin beta7(hi)
      CD16/32(hi) cells. Moreover, a major difference in maturity of these cells based
      on FcepsilonRI expression was observed between the Th2-prone BALB/c strain and
      the Th1-prone C57BL/6 strain (66% vs. 25% FcepsilonRI+, respectively). Therefore,
      the choice of mouse strain is critical when studying disease models such as
      experimental asthma where mast cells and their progenitors are involved.

PMID- 24112045
TI  - Novel multisensor probe for monitoring bladder temperature during locoregional
      chemohyperthermia for nonmuscle-invasive bladder cancer: technical feasibility
      study.
AB  - BACKGROUND AND PURPOSE: The effectiveness of locoregional hyperthermia combined
      with intravesical instillation of mitomycin C to reduce the risk of recurrence
      and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer
      is currently investigated in clinical trials. Clinically effective locoregional
      hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal
      thermometry methods are needed to monitor accurately the temperature distribution
      throughout the bladder wall. The aim of the study was to evaluate the technical
      feasibility of a novel intravesical device (multi-sensor probe) developed to
      monitor the local bladder wall temperatures during loco-regional C-HT. MATERIALS
      AND METHODS: A multisensor thermocouple probe was designed for deployment in the
      human bladder, using special sensors to cover the bladder wall in different
      directions. The deployment of the thermocouples against the bladder wall was
      evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine
      models, and human bladders obtained from obduction for bladder volumes and
      different deployment sizes of the probe. Finally, porcine bladders were embedded
      in a phantom and subjected to locoregional heating to compare probe temperatures
      with additional thermometry inside and outside the bladder wall. RESULTS: The 7.5
      cm thermocouple probe yielded optimal bladder wall contact, adapting to different
      bladder volumes. Temperature monitoring was shown to be accurate and
      representative for the actual bladder wall temperature. CONCLUSIONS: Use of this
      novel multisensor probe could yield a more accurate monitoring of the bladder
      wall temperature during locoregional chemohyperthermia.

PMID- 24112046
TI  - Discovery of novel bacterial RNA polymerase inhibitors: pharmacophore-based
      virtual screening and hit optimization.
AB  - The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum
      antibiotics. However, the efficiency of drugs is reduced by resistance. To
      discover novel RNAP inhibitors, a pharmacophore based on the alignment of
      described inhibitors was used for virtual screening. In an optimization process
      of hit compounds, novel derivatives with improved in vitro potency were
      discovered. Investigations concerning the molecular mechanism of RNAP inhibition
      reveal that they prevent the protein-protein interaction (PPI) between sigma(70)
      and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were
      shown to interfere with bacterial lipid biosynthesis. The compounds were active
      against Gram-positive pathogens and revealed significantly lower resistance
      frequencies compared to clinically used rifampicin. 

PMID- 24112048
TI  - Toward single-molecule microscopy on a smart phone.
AB  - Thanks to fluorescence, single nano-objects down to individual fluorophores can
      now be imaged in optical microscopes. Fluorescence imaging is still restricted to
      laboratory facilities as it usually involves expensive and bulky instrumentation.
      A report by Wei et al. in this issue of ACS Nano, however, shows that a
      sensitive, cost-effective, and portable device can be developed to image
      individual nano-objects as small as large viruses. This work opens the
      fascinating prospects of single-molecule microscopy and spectroscopy on a smart
      phone. We speculate on the possible applications of such a portable imaging
      device and on the perspectives it may open in different fields of science and
      technology. 

PMID- 24112047
TI  - Transcriptional reprogramming and stimulation of leaf respiration by elevated CO2
      concentration is diminished, but not eliminated, under limiting nitrogen supply.
AB  - Plant respiration responses to elevated CO2 concentration ( [CO2 ] ) have been
      studied for three decades without consensus about the mechanism of response.
      Positive effects of elevated [CO2 ] on leaf respiration have been attributed to
      greater substrate supply resulting from stimulated photosynthesis. Negative
      effects of elevated [CO2 ] on leaf respiration have been attributed to reduced
      demand for energy for protein turnover assumed to result from lower leaf N
      content. Arabidopsis thaliana was grown in ambient (370 ppm) and elevated (750
      ppm) [CO2 ] with limiting and ample N availabilities. The stimulation of leaf
      dark respiration was attenuated in limiting N (+12%) compared with ample N supply
      (+30%). This response was associated with smaller stimulation of photosynthetic
      CO2 uptake, but not interactive effects of elevated CO2 and N supply on leaf
      protein, amino acids or specific leaf area. Elevated [CO2 ] also resulted in
      greater abundance of transcripts for many components of the respiratory pathway.
      A greater transcriptional response to elevated [CO2 ] was observed in ample N
      supply at midday versus midnight, consistent with reports that protein synthesis
      is greatest during the day. Greater foliar expression of respiratory genes under
      elevated [CO2 ] has now been observed in diverse herbaceous species, suggesting a
      widely conserved response.

PMID- 24112049
TI  - Covalent thiol adducts arising from reactive intermediates of cocaine
      biotransformation.
AB  - Exposure to cocaine results in the depletion of hepatocellular glutathione and
      macromolecular protein binding in humans. Such cocaine-induced responses have
      generally been attributed to oxidative stress and reactive metabolites resulting
      from oxidative activation of the cocaine tropane nitrogen. However, little
      conclusive data exists on the mechanistic pathways leading to protein
      modification or the structure and specificity of cocaine-derived adduction
      products. We now report a previously uncharacterized route of cocaine
      bioactivation leading to the covalent adduction of biological thiols, including
      cysteine and glutathione. Incubation of cocaine with biological nucleophiles in
      an in vitro biotransformation system containing human liver microsomes identified
      a monooxygenase-mediated event leading to the oxidation of, and subsequent
      sulfhydryl addition to, the cocaine aryl moiety. Adduct structures were confirmed
      using ultra-high performance liquid chromatography coupled to high resolution,
      high mass accuracy mass spectrometry. Examination of assays containing transgenic
      bactosomes expressing single human cytochrome P450 isoforms determined the role
      of P450s 1A2, 2C19, and 2D6 in the oxidation process resulting in adduct
      formation. P450-catalyzed aryl epoxide formation and subsequent attack by free
      nucleophilic moieties is consistent with the resulting adduct structures,
      mechanisms of formation, and the empirical observation of multiple structural and
      stereo isomers. Analogous adduction mechanisms were maintained across all
      sulfhydryl-containing nucleophile models examined; N-acetylcysteine, glutathione,
      and a synthetic cysteine-containing hexapeptide. Predictive in silico
      calculations of molecular reactivity and electrophilicity/nucleophilicity were
      compared to the results of in vitro assay incubations in order to better
      understand the adduction process using the principles of hard and soft acid and
      base (HSAB) theory. This study elucidated a novel metabolic pathway that may be
      of particular significance to the clinical and forensic toxicology of cocaine and
      provides analytical tools and methods that can be applied to the determination of
      these conjugates in humans, opening a new area of research on cocaine
      biotransformation and toxicology. 

PMID- 24112050
TI  - Molecular imaging reveals time course of matrix metalloproteinase activity in
      acute cutaneous vasculitis in vivo.
AB  - Matrix metalloproteinases (MMPs) play a critical role in various pathological
      conditions including cutaneous inflammation. Thus far, serial assessment of MMP
      activity in ongoing inflammation is hampered due to technical limitations. Here,
      we present an innovative method for longitudinal detection of MMP activity by in
      vivo imaging. First, we analysed skin sections from patients suffering from
      leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via
      immunofluorescence staining. Then, we mimicked LcV in mice in a well-studied
      model of immune complex-mediated vasculitis (ICV). This acute inflammatory
      process was serially visualized in vivo using the fluorescence-labelled MMP
      tracer Cy5.5-AF443. The deposition of fluorescence-labelled immune complexes and
      MMP tracer distribution was visualized repeatedly and non-invasively by
      fluorescence reflectance imaging. In correlation with the presence of MMP-2 and
      MMP-9 in immunofluorescence stainings, Cy5.5-AF443 accumulated in ICV spots in
      the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice
      equipped with a dorsal skinfold chamber, where microscopic observations revealed
      an increased recruitment of fluorescence-labelled leucocytes during ICV. The
      specificity of the MMP tracer was supported by (i) analysis of mice deficient in
      functional beta2 -integrins (CD18(-/-) ) and (ii) subsequent MMP
      immunofluorescence staining. These findings let us conclude that MMP accumulation
      in the acute phase of ICV depends on beta2 -mediated leucocyte recruitment. In
      summary, we show that MMPs are involved in ICV as determined by Cy5.5-AF443, a
      new optical marker to longitudinally and non-invasively follow MMP activity in
      acute skin inflammation in vivo. 

PMID- 24112051
TI  - The state of innovative emergency medical service programs in the United States.
AB  - BACKGROUND: The primary objective of this study was to determine how EMS
      organizations that are piloting patient-centered treatment and transport
      protocols are approaching the challenges of implementation, reimbursement, and
      quality assurance. We were particularly interested in determining if these pilot
      efforts have raised any patient safety concerns. METHODS: We conducted a set of
      discussions with a small group of key EMS stakeholders regarding the status of
      pioneering efforts to develop and evaluate innovative approaches to EMS in the
      United States. RESULTS: We had discussions with 9 EMS agencies to better
      understand their innovative programs, including: the history of their service
      policy and procedure for transports that do not require emergency department
      care; the impact of their innovative program on service costs and/or cost
      savings; any reimbursement issues or changes; patient safety; patient
      satisfaction; and overall impression as well as recommendations for other EMS
      systems considering adoption of this policy. CONCLUSIONS: In general, EMS systems
      are not reimbursed for service unless the patient is transported to an ED.
      Spokespersons for all nine sites covered by this project said that this policy
      creates a powerful disincentive to implementing pilot programs to safely reduce
      EMS use by directing patients to more appropriate sites of care or proactively
      treating them in their homes. Even though private and public hospitals and payers
      typically benefit from these programs, they have been generally reluctant to
      offer support. This raises serious questions about the long-term viability of
      these programs.

PMID- 24112052
TI  - Substituent Effect on the Photolability of 4-Aryl-1,4-Dihydropyridines.
AB  - The electronic nature of substituents attached to the 4-aryl moiety of 1,4
      dihydropyridines strongly affects the photophysical and photochemical behavior of
      these family of compounds. The presence of an electron donor substituent on the 4
      aryl moiety (or the absence of electron-withdrawing ones) modifies the
      luminescence lifetimes (tau < 100 ps) and diminishes the photodecomposition
      quantum yields. For electron-withdrawing substituents, the photodegradation
      quantum yield is affected by the media, changing more than two orders of
      magnitude as the polarity is increased. Studies in micellar media allow us to
      conclude that 4-aryl-1,4-dihydropyridines are located near to the interface;
      however, the surface charge of micelles has no effect on the photodegradation
      rate constant or the photoproducts profile. The main conclusion of this work is
      that the photolability of 4-aryl-1,4-dihydropyridines can be significantly
      reduced by the incorporation of antioxidant moieties.

PMID- 24112053
TI  - Major faecal microbiota shifts in composition and diversity with age in a
      geographically restricted cohort of mothers and their children.
AB  - Despite the importance, the diversity of the human infant gut microbiota still
      remains poorly characterized at the regional scale. Here, we investigated the
      faecal microbiota diversity in a large 16S rRNA gene data set from a healthy
      cohort of 86 mothers and their children from the Trondheim region in Norway.
      Samples were collected from mothers during early and late pregnancy, as well as
      from their children at 3 days, 10 days, 4 months, 1 year and 2 years of age.
      Using a combination of Sanger sequencing of amplicon mixtures (without cloning),
      real-time quantitative PCR and deep pyrosequencing, we observed a clear age
      related colonization pattern in children that was surprisingly evident between 3-
      and 10-day samples. In contrast, we did not observe any shifts in microbial
      composition during pregnancy. We found that alpha-diversity was highest at 2
      years and lowest at 4 months, whereas beta-diversity estimates indicated highest
      interindividual variation in newborns. Variation significantly decreased by the
      age of 10 days and was observed to be convergent over time; however, there were
      still major differences between 2 years and adults whom exhibited the lowest
      interindividual diversity. Taken together, the major age-affiliated population
      shift within gut microbiota suggests that there are important mechanisms for
      transmission and persistence of gut bacteria that remain unknown.

PMID- 24112054
TI  - Phenotypic expression of Hb F in common high Hb F determinants in Thailand: roles
      of alpha-thalassemia, 5' delta-globin BCL11A binding region and 3' beta-globin
      enhancer.
AB  - BACKGROUND: Deletions of delta- and beta-globin genes are associated with
      different Hb F levels. To address this, we have examined hematological and
      molecular characteristics in a large cohort of high Hb F determinants in
      Thailand. METHODS: A total of 160 unrelated adult subjects with heterozygous
      trait for high Hb F determinants and another 10 patients with compound
      heterozygous trait for Hb E were selectively recruited. Hematological parameters
      and Hb analysis were recorded, and alpha-thalassemia mutations were investigated.
      DNA deletions causing deltabeta(0) -thalassemia and hereditary persistence of
      fetal hemoglobin (HPFH) were identified using multiplex PCR and denaturing high
      performance liquid chromatography (HPLC) assays developed. RESULTS: Four
      different DNA deletions were detected including the 12.6 kb deletion deltabeta(0)
      -thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)-6
      (n = 65), Indian deletion-inversion (G) gamma((A) gammadeltabeta)-thalassemia (n
      = 15) and 78 kb deletion Chinese (G) gamma((A) gammadeltabeta)-thalassemia (n =
      1). Eighteen cases were found to carry alpha-thalassemia with 10 different
      genotypes. All 10 patients who had similar hematological phenotype with that of
      Hb E-beta(0) -thalassemia were found to be compound Hb E-deltabeta(0) 
      thalassemia. Differences in hematological features as well as Hb F levels were
      noted and are presented comparatively. CONCLUSION: Comparison of phenotypes,
      genotypes, and the deletion breakpoints of these Thai high Hb F determinants
      indicates that differences in Hb F expression are correlated with the existence
      of alpha-thalassemia, the loss of BCL11A binding region located 5' to the delta
      globin gene and the 3' beta-globin enhancer, which confirms their important roles
      in fetal Hb expression.

PMID- 24112055
TI  - Comparison of hydrophobic properties of thoracic duct lymph chylomicrons from
      rats given different fats or oils by gavage.
AB  - Lipoprotein aggregation is generated by hydrophobic nature of lipoproteins that
      is known to be one of the causes of atherosclerosis. Low density lipoproteins
      (LDL) has been extensively studied in this respect but not chylomicrons. There is
      strong evidence that post-prandial triacylglycerol-rich lipoproteins are
      atherogenic. Because biophysical properties of lipoproteins are largely
      determined by their lipid compositions, hydrophobic nature of thoracic lymph duct
      chylomicrons obtained from rats given different fats or oils by gavage was
      investigated by vortexing-induced aggregation and hydrophobic interaction
      chromatography. Contrary to LDL, vortexing did not cause aggregation in
      chylomicrons. Vortexing of fish oil and butter chylomicrons resulted in more
      prominent reduction in absorbances compared with chylomicrons from other sources
      that might indicate less micelle stability. Hydrophobic interaction
      chromatography of fish oil, palm oil and olive oil chylomicrons yielded three
      fractions, whereas that of sunflower, margarine and butter chylomicrons gave rise
      to two fractions. These results suggest that surface hydrophobicity of
      chylomicrons might be heterogenous. Our results also demonstrate that fish oil
      chylomicrons have less hydrophobicity and lower stability against vortexing
      compared with chylomicrons from other sources. Considering beneficial effects of
      fish oil in cardiovascular health, less hydrophobicity together with lower
      stability might provide an additional atherogeneicity index for lipoproteins. 

PMID- 24112056
TI  - Five years of progress: a road map for the future.

PMID- 24112057
TI  - Tribute to Surgeon General Regina Benjamin, MD.

PMID- 24112058
TI  - Growing a First Food movement.

PMID- 24112059
TI  - Donor human milk banking: growth, challenges, and the role of HMBANA.

PMID- 24112060
TI  - Increasing the global supply and affordability of donor milk.

PMID- 24112061
TI  - National-level leadership in support of breastfeeding.

PMID- 24112062
TI  - (Not) breastfeeding in the low-wage, non-union American workplace.

PMID- 24112063
TI  - Mothers' costs of suboptimal breastfeeding: implications of the maternal disease
      cost analysis.

PMID- 24112064
TI  - The case for creating a model insurance policy: payer coverage of breastfeeding
      counseling services, pumps, and supplies.
AB  - With the implementation of the Health Resources and Services Administration
      Women's Preventive Services Guidelines, which went into effective August 1, 2012,
      under the Affordable Care Act, healthcare insurance companies across the country
      have interpreted the breastfeeding support provision in a variety of ways. In
      order to improve benefit design and promote transparency and accountability, the
      National Breastfeeding Center and the United States Breastfeeding Committee co
      authored a model insurance policy that seeks to educate insurance executives
      about appropriately supporting breastfeeding medicine for purposes of improving
      population health.

PMID- 24112065
TI  - Reaching Our Sisters Everywhere.

PMID- 24112066
TI  - Infant feeding in America: enough to break a mother's heart?
AB  - Cardiovascular disease is a leading cause of death of women around the world.
      Diet, exercise, smoking cessation, and blood pressure control are all recognized
      as key elements of preventing cardiovascular disease. Infant feeding has received
      less attention, but the studies reviewed here indicate that lactation may also
      play an important role in determining women's future risk of heart disease. A
      growing body of literature indicates that mothers who prematurely discontinue
      lactation face increased risk of visceral adiposity, hypertension,
      hyperlipidemia, diabetes, and subclinical cardiovascular disease, as well as
      cardiovascular morbidity and mortality. Breastfeeding is not always easy, but
      neither is dieting, exercise, smoking cessation, or treating hypertension. In
      order to effectively fight heart disease, efforts are needed to promote all
      aspects of a healthy lifestyle, which for women includes breastfeeding their
      babies.

PMID- 24112070
TI  - Groundwater uranium origin and fate control in a river valley aquifer.
AB  - Groundwater in a Quaternary gravel aquifer partly exhibits uranium (U)
      concentrations exceeding the new German drinking water limitation (22% of the
      samples >10 MUg L(-1)). This study assesses relevant U reservoirs and
      hydrogeochemical processes responsible for U transfer between them. A large data
      set of solid materials (sediments and soils, 164 samples total) and groundwater
      (114 samples total) characteristics was created in terms of geo- and
      hydrochemistry, mineralogy, U microdistribution, and mobilization potential.
      Results show that U primarily derived from lignitic inclusions in Tertiary
      sediments is transported to and accumulated (complexation to organic substance
      and UO2 precipitation) in lowland moor peats of the river valley grown on the
      aquifer gravels. The alkaline character of the system predefines a
      hydrogeochemical framework fostering U mobility. Elevated concentrations (up to
      96 MUg L(-1) U) occur downstream of the moor areas and under Mn/NO3-reducing
      groundwater conditions. Oxic and stronger reduced settings are rather little
      affected. Supporting previous laboratory studies, this suggests enhanced U
      mobility in the presence of nitrate also in the field scale. While no
      anthropogenic U input was detected in the study area, agricultural usage of the
      moor areas triggers geogenic U release via nitrate fertilization, surface peat
      degradation, and erosion. 

PMID- 24112071
TI  - Melatonin and the theories of aging: a critical appraisal of melatonin's role in
      antiaging mechanisms.
AB  - The classic theories of aging such as the free radical theory, including its
      mitochondria-related versions, have largely focused on a few specific processes
      of senescence. Meanwhile, numerous interconnections have become apparent between
      age-dependent changes previously thought to proceed more or less independently.
      Increased damage by free radicals is not only linked to impairments of
      mitochondrial function, but also to inflammaging as it occurs during immune
      remodeling and by release of proinflammatory cytokines from mitotically arrested,
      DNA-damaged cells that exhibit the senescence-associated secretory phenotype
      (SASP). Among other effects, SASP can cause mutations in stem cells that reduce
      the capacity for tissue regeneration or, in worst case, lead to cancer stem
      cells. Oxidative stress has also been shown to promote telomere attrition.
      Moreover, damage by free radicals is connected to impaired circadian rhythmicity.
      Another nexus exists between cellular oscillators and metabolic sensing, in
      particular to the aging-suppressor SIRT1, which acts as an accessory clock
      protein. Melatonin, being a highly pleiotropic regulator molecule, interacts
      directly or indirectly with all the processes mentioned. These influences are
      critically reviewed, with emphasis on data from aged organisms and senescence
      accelerated animals. The sometimes-controversial findings obtained either in a
      nongerontological context or in comparisons of tumor with nontumor cells are
      discussed in light of evidence obtained in senescent organisms. Although, in
      mammals, lifetime extension by melatonin has been rarely documented in a fully
      conclusive way, a support of healthy aging has been observed in rodents and is
      highly likely in humans. 

PMID- 24112072
TI  - Evaluation of probiotics in diets with different nutrient densities on growth
      performance, blood characteristics, relative organ weight and breast meat
      characteristics in broilers.
AB  - 1. A total of 720 1-d-old broilers were used in a 28 d experiment to determine
      the effects of probiotic supplementation in diets with different dietary nutrient
      densities. 2. Birds were randomly allotted to one of the 4 treatments in a 2 * 2
      factorial arrangement (12 replicateswith 15 broilers per replicate) with two
      levels of nutrient density [high nutrient density (metabolisable energy (ME) 12.7
      MJ/kg and crude protein (CP) 230.3 g/kg for 1-7 d; ME 13.2 MJ/kg and CP 220.3
      g/kg for 8-28 d) or low nutrient density (ME 12.1 MJ/kg and CP 220.2 g/kg for 0-7
      d; ME 12.6 MJ/kg and CP 209.8 g/kg for 8-28 d)] and 0 or 2 g/kg probiotics (1.0 *
      10(10) viable spores/g of Bacillus subtilis endospores and 1.0 * 10(9) viable
      spores/g of Clostridium butyricum). 3. The high-nutrient-density diet increased
      body weight gain (BWG), feed conversion ratio (FCR), serum cholesterol and
      triglyceride concentration relative to the low-nutrient-density diet. High
      nutrient-density diet reduced water loss ratio of breast muscle, liver and fat
      relative to body weight compared to low-nutrient density-diet. The inclusion of
      probiotics increased BWG and feed intake throughout the experiment. Dietary
      probiotics increased the percentage of blood lymphocytes and relative weight of
      spleen and bursa of Fabricius when compared to the non-probiotic treatment. The
      inclusion of probiotics decreased serum cholesterol and triglyceride
      concentrations and lightness (L*) value of breast meat compared to the non
      probiotic-supplemented diet. 4. In conclusion, high dietary nutrient density
      increased growth performance and serum cholesterol and triglyceride
      concentrations in broiler chickens. The inclusion of probiotics increased growth
      performance but reduced serum cholesterol and triglyceride concentrations. The
      positive effect of probiotic supplementation on growth performance was reduced by
      the high-nutrient-density diet during the first week of life. 

PMID- 24112073
TI  - Effective therapy with proton irradiation for oral melanoma.

PMID- 24112074
TI  - Developing metapopulation connectivity criteria from genetic and habitat data to
      recover the endangered Mexican wolf.
AB  - Restoring connectivity between fragmented populations is an important tool for
      alleviating genetic threats to endangered species. Yet recovery plans typically
      lack quantitative criteria for ensuring such population connectivity. We
      demonstrate how models that integrate habitat, genetic, and demographic data can
      be used to develop connectivity criteria for the endangered Mexican wolf (Canis
      lupus baileyi), which is currently being restored to the wild from a captive
      population descended from 7 founders. We used population viability analysis that
      incorporated pedigree data to evaluate the relation between connectivity and
      persistence for a restored Mexican wolf metapopulation of 3 populations of equal
      size. Decreasing dispersal rates greatly increased extinction risk for small
      populations (<150-200), especially as dispersal rates dropped below 0.5
      genetically effective migrants per generation. We compared observed migration
      rates in the Northern Rocky Mountains (NRM) wolf metapopulation to 2 habitat
      based effective distance metrics, least-cost and resistance distance. We then
      used effective distance between potential primary core populations in a restored
      Mexican wolf metapopulation to evaluate potential dispersal rates. Although
      potential connectivity was lower in the Mexican wolf versus the NRM wolf
      metapopulation, a connectivity rate of >0.5 genetically effective migrants per
      generation may be achievable via natural dispersal under current landscape
      conditions. When sufficient data are available, these methods allow planners to
      move beyond general aspirational connectivity goals or rules of thumb to develop
      objective and measurable connectivity criteria that more effectively support
      species recovery. The shift from simple connectivity rules of thumb to species
      specific analyses parallels the previous shift from general minimum-viable
      population thresholds to detailed viability modeling in endangered species
      recovery planning.

PMID- 24112075
TI  - Lipid composition of some commonly consumed traditional Nigerian dishes.
AB  - BACKGROUND: Lipids in the diet have been associated with the rising prevalence of
      many chronic diseases. The present study aimed to provide information on total
      lipid, free fatty acids, triacylglycerol and cholesterol contents of some dishes
      consumed in northern, southern, western parts of Nigeria, as well as dishes
      generally consumed in all parts of Nigeria. This would result in a resource that
      would be used by nutritionists and dietitians in meal planning. METHODS: The
      present study is analytical in nature. The composite dishes included a blend of
      cereals, roots and tubers, legumes, fat and oil and vegetables and were analysed
      for total lipid, free fatty acids, triacylglycerol and cholesterol contents
      spectrophotometrically. RESULTS: Burabisko (a millet based dish) had the lowest
      free fatty acid (0.1 mg per 100 g) and cholesterol (1. 9 mg per 100 g) contents,
      yam with eggs (7.1 mg per 100 g) and miyan-kuka with semovita (415.9 mg per 100
      g) contained the highest amounts of free fatty acid and cholesterol,
      respectively. The total lipid and triacylglycerol content were lowest in gbegiri
      with eko (2.6 g per 100 g) and 3.1 mg per 100 g respectively. Stewed beans with
      fried plantain, however, had the highest total lipid (86.5 g per 100 g) content
      and yam with eggs had the highest triacylglycerol (122.5 mg per 100 g) contents.
      The moisture content of the dishes ranged between 59.68 and 81.73% in melon seed
      with vegetable soup and burabisko, respectively. CONCLUSIONS: For the first time,
      we have provided the lipid profile of standardised traditional dishes consumed in
      Nigeria. These dishes contribute a significant proportion of lipids to the diet
      of Nigerians, which are essential for assessing the nutrient intake of Nigerians.

PMID- 24112076
TI  - Isometric torso muscle endurance profiles in adolescents aged 15-18: normative
      values for age and gender differences.
AB  - OBJECTIVE: The aim of this study was to establish normative values for torso
      muscle endurance in adolescents aged 15-18 years. It was hypothesized that torso
      endurance profiles of adolescents differs between males and females and between
      adolescents and adults. BACKGROUND: Decreased torso muscle endurance has been
      identified as a potential personal risk factor for low back pain development in
      both adolescents and later years together with being detrimental for athletic
      performance. DESIGN: Measurement of torso muscle endurance, established through
      four tests performed in random order in a healthy adolescent population. SETTING:
      High school in Novi Sad, Province of Vojvodina, Republic of Serbia. METHODS: Two
      hundred and ninety-four adolescents from one high school (178 males and 116
      females) were grouped into four age strata. Selected isometric torso muscle
      endurance tests were: Biering-Sorensen test for extensor endurance; Flexor
      endurance test; right and left Side Bridge tests. The mean, ratio, standard
      deviation and 25th, 50th and 75th percentile scores were determined for each
      gender/age strata. RESULTS AND CONCLUSION: Males had higher lateral torso
      endurance than females. Adolescents in general demonstrate their peak lifetime
      endurance as they appear more endurable than children and comparable adult
      groups. These data of endurance times, their ratios and percentiles in healthy
      normal subjects form a database bridging existing data for children and adults
      that may be useful for guiding training and rehabilitation.

PMID- 24112077
TI  - Anaphylactic responses to histamine in mice utilize both histamine receptors 1
      and 2.
AB  - BACKGROUND: Anaphylaxis is a severe, potentially life-threatening reaction that
      can occur in response to common triggers, including food allergens (e.g.,
      peanut), insect stings, and several medications. Activation of mast cells and
      basophils to release preformed mediators, such as histamine, is thought to be an
      important process that underlies reactions. Histamine can exert effects through
      four different receptors, termed H1R-H4R. Despite clinical use of both H1R and
      H2R blockers in the therapy for acute allergic reactions, there is little
      mechanistic evidence to support the necessity for blocking H2R, a receptor best
      characterized for its role in stomach acid production. METHODS: Here, we sought
      to define the necessity for histamine receptors in the pathology of anaphylaxis
      using H1R and H2R knockout (KO) mice, as well as a H1R/H2R double KO strain.
      RESULTS: In response to IgE-mediated systemic anaphylaxis, the symptoms and
      decreases in core body temperature observed in wild-type mice were reduced but
      not ablated in either H1R or H2R KO. In contrast, H1R/H2R KO were significantly
      protected and were indistinguishable from histamine-deficient mice. Intravenous
      injection of histamine was sufficient to elicit these responses, and similar to
      IgE-mediated anaphylaxis, loss of both H1R and H2R was necessary for complete
      protection. CONCLUSION: Our data demonstrate definitively that both H1R and H2R
      participate in the immediate systemic responses during histamine-associated
      pathophysiology and mechanistically support the utility of H2R-blocking
      therapeutics in alleviating symptoms of anaphylaxis.

PMID- 24112078
TI  - Hepcidin decreases over the first year of life in healthy African infants.

PMID- 24112080
TI  - Soluble TWEAK plasma levels increase after renal transplantation and associate
      with the improvement of endothelial function.
AB  - BACKGROUND: Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA)
      concentrations have been associated with endothelial function in patients with
      chronic kidney disease (CKD). We tested the hypothesis that the improvement in
      endothelial function observed after renal transplantation is directly linked to
      the normalization of both sTWEAK and ADMA. MATERIALS AND METHODS: One hundred and
      seventy-five kidney transplant recipients (71% men; 31.6 +/- 9.4 years) were
      studied immediately before and on the 180th day post-transplantation. At each
      visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA.
      Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also
      performed. RESULTS: Renal transplantation was followed by an improvement in FMD.
      This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA
      after transplantation (P < 0.001 for all). Cross-sectionally, both molecules
      associated with FMD before as well as after transplantation (P < 0.001 for all).
      Longitudinally, the changes observed in sTWEAK (beta = 0.26, P < 0.001) and ADMA
      (beta = -0.44, P < 0.001) levels were independently associated with the
      improvement of FMD (r(2)  = 0.30). CONCLUSIONS: Renal transplantation is followed
      by an improvement of FMD that is independently associated with the normalization
      of both sTWEAK and ADMA concentrations. We identify two surrogate biomarkers of
      endothelial function with potential as therapeutic targets.

PMID- 24112079
TI  - Skype me! Socially contingent interactions help toddlers learn language.
AB  - Language learning takes place in the context of social interactions, yet the
      mechanisms that render social interactions useful for learning language remain
      unclear. This study focuses on whether social contingency might support word
      learning. Toddlers aged 24-30 months (N = 36) were exposed to novel verbs in one
      of three conditions: live interaction training, socially contingent video
      training over video chat, and noncontingent video training (yoked video). Results
      suggest that children only learned novel verbs in socially contingent
      interactions (live interactions and video chat). This study highlights the
      importance of social contingency in interactions for language learning and
      informs the literature on learning through screen media as the first study to
      examine word learning through video chat technology.

PMID- 24112081
TI  - Moderating mycorrhizas: arbuscular mycorrhizas modify rhizosphere chemistry and
      maintain plant phosphorus status within narrow boundaries.
AB  - Pastures often experience a pulse of phosphorus (P) when fertilized. We examined
      the role of arbuscular mycorrhizal fungi (AMF) in the uptake of P from a pulse.
      Five legumes (Kennedia prostrata, Cullen australasicum, Bituminaria bituminosa,
      Medicago sativa and Trifolium subterraneum) were grown in a moderate P,
      sterilized field soil, either with (+AMF) or without (-AMF) addition of
      unsterilized field soil. After 9-10 weeks, half the pots received 15 mg P kg(-1)
      of soil. One week later, we measured: shoot and root dry weights; percentage of
      root length colonized by AMF; plant P, nitrogen and manganese (Mn)
      concentrations; and rhizosphere carboxylates, pH and plant-available P. The P
      pulse raised root P concentration by a similar amount in uncolonized and
      colonized plants, but shoot P concentration increased by 143% in uncolonized
      plants and 53% in colonized plants. Inoculation with AMF decreased the amount of
      rhizosphere carboxylates by 52%, raised rhizosphere pH by ~0.2-0.7 pH units and
      lowered shoot Mn concentration by 38%. We conclude that AMF are not simply a
      means for plants to enhance P uptake when P is limiting, but also act to maintain
      shoot P within narrow boundaries and can affect nutrient uptake through their
      influence on rhizosphere chemistry.

PMID- 24112082
TI  - The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric
      oxide synthase dysfunction.
AB  - Smokers have an elevated risk of cardiovascular disease but the origin(s) of this
      increased risk are incompletely defined. Considerable evidence supports an
      accumulation of the oxidant-generating enzyme MPO (myeloperoxidase) in the
      inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO
      substrate, with this resulting in HOSCN (hypothiocyanous acid) formation. We
      hypothesized that this thiol-specific oxidant may target the Zn(2+)-thiol cluster
      of eNOS (endothelial nitric oxide synthase), resulting in enzyme dysfunction and
      reduced formation of the critical signalling molecule NO*. Decreased NO*
      bioavailability is an early and critical event in atherogenesis, and HOSCN
      mediated damage to eNOS may contribute to smoking-associated disease. In the
      present study it is shown that exposure of isolated eNOS to HOSCN or
      MPO/H2O2/SCN(-) decreased active dimeric eNOS levels, and increased inactive
      monomer and Zn(2+) release, compared with controls, HOCl (hypochlorous acid)- or
      MPO/H2O2/Cl(-)-treated samples. eNOS activity was increasingly compromised by
      MPO/H2O2/Cl(-) with increasing SCN(-) concentrations. Exposure of HCAEC (human
      coronary artery endothelial cell) lysates to pre-formed HOSCN, or MPO/H2O2/Cl(-)
      with increasing SCN(-), increased eNOS monomerization and Zn(2+) release, and
      decreased activity. Intact HCAECs exposed to HOCl and HOSCN had decreased eNOS
      activity and NO2(-)/NO3(-) formation (products of NO* decomposition), and
      increased free Zn(2+). Exposure of isolated rat aortic rings to HOSCN resulted in
      thiol loss, and decreased eNOS activity and cGMP levels. Overall these data
      indicate that high SCN(-) levels, as seen in smokers, can increase HOSCN
      formation and enhance eNOS dysfunction in human endothelial cells, with this
      potentially contributing to increased atherogenesis in smokers.

PMID- 24112083
TI  - On preserving a legacy: Paul Lerner and the Menninger Rorschach tradition.
AB  - Paul Lerner's contributions to the Rorschach test were rooted in a psychoanalytic
      approach to diagnostic testing that began with David Rapaport at the Menninger
      Clinic in the 1940s. This article reviews the work of Rapaport, Roy Schafer, and
      their heirs and shows how Lerner's career was devoted to advancing that tradition
      and assuring its continuing relevance. 

PMID- 24112084
TI  - The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA
      transporter activities.
AB  - The neurotransmitter transporters of the SLC6 family play critical roles in the
      regulation of neurotransmission and are the primary targets of therapeutic agents
      used to treat clinical disorders involving compromised neurotransmitter
      signaling. The dopamine and norepinephrine transporters have been implicated in
      clinical disorders such as attention deficit hyperactivity disorder (ADHD) and
      substance abuse. The GABA transporters (GATs) serve as a target for anxiolytic,
      antidepressant, and antiepileptic therapies. In this work, the interaction with
      neurotransmitter transporters was characterized for a derivative of the lignan (
      )-cubebin (1), namely, (-)-hinokinin (2). Using in vitro pharmacological assays,
      2 selectively inhibited the human dopamine and norepinephrine transporters, in a
      noncompetitive manner possibly mediated by binding to a novel site within the
      transporters, and displayed low affinity for the serotonin transporter. Compound
      2 also specifically inhibited the GAT-1 GABA transporter subtype. Compound 2 is
      not a substrate of the carriers as it had no effect on the efflux of either of
      the neurotransmitters investigated. This compound is inactive toward glutamate
      and glycine transporters. These results suggest that 2 may serve as a tool to
      develop new therapeutic drugs for ADHD and anxiety that target the DAT, NET, and
      GAT-1 transporters. 

PMID- 24112085
TI  - Validation of the Spanish version of Ureteral Stent Symptom Questionnaire:
      prevalence of symptoms in a tertiary care center in Mexico.
AB  - OBJECTIVES: To develop and to validate the Spanish version of the Ureteral Stent
      Symptom Questionnaire (USSQ). Describe the prevalence of symptoms associated with
      the presence of ureteral stent in a Spanish-speaking population. METHODS: We
      developed and delivered the Spanish USSQ version to patients who underwent
      ureteral stent placement after endourological procedures. We determined the
      internal consistency and the instrument's sensitivity to change. Results of the
      patients were compared with a control group of healthy individuals. We analyzed
      the prevalence of symptoms in the six domains of the questionnaire and the
      overall quality of life. We compared the means of the results by gender to find
      significant differences in associated symptoms. RESULTS: We obtained good
      internal consistency values of the instrument. Significant differences were
      obtained after sensitivity to change analysis in the scores of all domains except
      sexual performance. The correlation between the domains of urinary symptoms,
      pain, and general health was high. The analysis of specific symptoms showed
      important affection in all domains, being more significant in urinary symptoms
      and pain. The ureteral catheter also affected the daily life and work
      performance. There were no significant differences when comparing the symptoms by
      gender or age. CONCLUSIONS: Spanish version of the USSQ is appropriate for
      assessing the symptoms associated with ureteral stent in the Spanish-speaking
      population. The ureteral catheter significantly affects the various aspects of
      life in this population.

PMID- 24112087
TI  - Identification and characterization of a novel porcine endothelial cell-specific
      Tie1 promoter.
AB  - BACKGROUND: The use of a transgenic pig for xenotransplantation and as a
      cardiovascular disease model has caught much attention in the past decades. The
      vascular endothelial cell is the primary modification target for the application
      of genetically modified pigs in this field. However, the powerful porcine
      endothelial cell-specific promoter is still so rare that the mouse and human
      promoters are commonly used. In the study, the porcine Tie1 (sTie1) promoter was
      identified and characterized as a potential endothelial cell-specific promoter to
      generate a cardiovascular disease model. METHODS: Tie1 promoters with different
      lengths of 5'-regulatory regions were cloned, and major putative DNA-binding
      motifs were mutated by site-directed mutagenesis. All fragments were ligated into
      the luciferase reporter system and were transiently transfected into endothelial
      cells to identify luciferase activity using a dual luciferase reporter assay.
      RESULTS: The luciferase activities of sTie1 promoters with different lengths of
      the 5'-regulatory region were tested. Results showed that the luciferase activity
      of the 1234-bp sTie1 fragment was the strongest compared with that of others (P <
      0.001). Site-directed mutagenesis in transcription-factor-binding sites,
      including Ets, GATA, and AP2, verified their key roles in regulating
      transcription, especially sites Ets (-103), GATA (-211), and AP2 (-3). The
      activities of Tie1 promoters from pig, human, and mouse were significantly
      different in pig iliac endothelial cells (PIECs) (P < 0.001), and the sTie1
      promoter showed the highest activity. Moreover, sTie1 promoter activity could be
      detected in porcine embryo fibroblasts and skeletal muscle cells. CONCLUSIONS:
      The sTie1 promoter shows a highly conserved sequence compared with the Tie1
      promoters in human and mouse, but it has a greater activity in the porcine
      endothelial cell line than that of human and mouse promoters. Thus, sTie1 will be
      a valuable tool for generating a pig cardiovascular disease model.

PMID- 24112086
TI  - Photophysics of glycosylated derivatives of a chlorin, isobacteriochlorin and
      bacteriochlorin for photodynamic theragnostics: discovery of a two-photon
      absorbing photosensitizer.
AB  - The photophysical properties of a chlorin, isobacteriochlorin and bacteriochlorin
      built on a core tetrapentafluorophenylporphyrin (TPPF20 ) and the nonhydrolyzable
      para thioglycosylated conjugates of these chromophores are presented. The
      photophysical characterization of these compounds was done in three different
      solvents to correlate with different environments in cells and tissues. Compared
      with TPPF20 other dyes have greater absorption in the red region of the visible
      spectrum and greater fluorescence quantum yields. The excited state lifetimes are
      from 3 to 11 ns. The radiative and nonradiative rate constants for deactivation
      of the excited state were estimated from the fluorescence quantum yield and
      excited state lifetime. The data indicate that the bacteriochlorin has strong
      absorption bands near 730 nm and efficiently enters the triplet manifold. The
      isobacteriochlorin has a 40-70% fluorescence quantum yield depending on solvent,
      so it may be a good fluorescent tag. The isobacteriochlorins also display
      enhanced two-photon absorption, thereby allowing the use of 860 nm light to
      excite the compound. While the two-photon cross section of 25 GM units is not
      large, excitation of low chromophore concentrations can induce apoptosis. The
      glycosylated compounds accumulate in cancer cells and a head and neck squamous
      carcinoma xenograft tumor model in mice. These compounds are robust to
      photobleaching.

PMID- 24112088
TI  - The impact of lymph vascular space invasion on recurrence and survival in
      patients with early stage endometrial cancer.
AB  - The aim of this study was to determine impact of lymph vascular space involvement
      (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991
      through 2010, all endometrial cancer patients at University Hospital of Bari,
      Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for
      time-to-event analysis to evaluate the effects of on lymph vascular space
      involvement recurrence rate and survival time. Of the 560 endometrial cancer
      patients, 525 underwent primary surgery. Of those, 399 had early stage disease.
      Three hundred and forty women were not found to have LVSI, whereas 59 were found
      to have lymph vascular space involvement. Forty-nine (12%) patients developed a
      recurrence and 20 of them showed lymph vascular space involvement. The
      statistical analysis demonstrated that LVSI was strongly associated with a poor
      survival (P < 0.0001). Lymph vascular space involvement is associated with a high
      risk of recurrence and poor overall survival in early stage of endometrial
      cancer; therefore, the clinical decision to decide whether or not a patient with
      early stage endometrial cancer should receive adjuvant therapy should be included
      the evaluation of lymph vascular space involvement. 

PMID- 24112089
TI  - Urinary incontinence among adult women with diabetes in Jordan: epidemiology,
      correlates and perceived impact on emotional and social well-being.
AB  - AIMS AND OBJECTIVES: To assess the epidemiology and correlates of urinary
      incontinence and its perceived impact on the emotional and social well-being of
      Jordanian women. BACKGROUND: Diabetes is a chronic disease with rising prevalence
      in women worldwide. Although urinary incontinence is a complication of diabetes,
      it is not commonly assessed with limited nurses' knowledge available on its
      prevalence, correlates and its perceived impact on lives of women. DESIGN: A
      cross-sectional survey design using probability sampling approach was used to
      collect information on incontinence. METHODS: A total of 1011 adult women, 20-65
      years old, attending primary healthcare centres in Jordan were interviewed using
      a standardised incontinence questionnaire. Questionnaire included items to assess
      the perceived impact of incontinence on social and emotional well-being of women.
      The study outcome included weekly or more any, stress and urge incontinence.
      RESULTS: Of 435 (43%) diabetic and 576 (57%) nondiabetic women, a total of 676
      (66.8%) women reported incontinence. The prevalence of weekly or more any, urge
      and stress incontinence was significantly higher in diabetic than in nondiabetic
      women, 31.5, 13.8 and 20% versus 18.2, 5.9 and 14.2%, respectively. After
      adjusting for age, body mass index, parity and history of urinary tract
      infections, in multiple logistic regression analyses, diabetes was significantly
      associated with any (OR: 1.99; 95% CI: 1.44-2.74) urge (OR: 2.23; 95% CI: 1.38
      3.61) and stress incontinence (OR: 1.54; CI: 1.07-2.22). Obesity and age were
      found to be significant correlates for urge incontinence in diabetics. Women with
      incontinence perceived incontinence as bothersome condition with negative impact
      on social well-being. CONCLUSIONS: Incontinence is a common and distressing
      problem in diabetic women, especially for those who are older and obese.
      Prospective cohort studies are needed to assess how nurse-led interventions may
      impact the negative consequences of incontinence on women well-being. RELEVANCE
      TO CLINICAL PRACTICE: Nurses are in the right position to assess urinary
      incontinence in diabetic women. Proper communications, culturally sensitive
      screening and tailored interventions may assist nurses in providing care and
      support to alleviate the impact of incontinence on women well-being.

PMID- 24112090
TI  - Synthesis of new dipyrido-annulated N-heterocyclic carbenes with ortho
      substituents.
AB  - A method for the introduction of various substituents at the 4 and 8 positions of
      2,10-di-tert-butyldipyrido[1,2-c;2',1'-e]imidazolium salts, is described. The new
      imidazolium salts bearing substituents (R' = Cl, SPh) at the 4 and 8 positions
      are synthesized in three-step procedures, and carbenes generated from the
      imidazolium salts can be used to give the corresponding rhodium complexes. The
      role of the 4,8-substituents can be either bystanders or coordinating ligands
      according to the nature of the metal moiety. 

PMID- 24112092
TI  - Mammalian target of rapamycin inhibitor rapamycin enhances anti-leukemia effect
      of imatinib on Ph+ acute lymphoblastic leukemia cells.
AB  - BCR-ABL fusion gene typically causes a type of acute lymphoblastic leukemia
      (ALL), known as Ph+ ALL. Although imatinib (IM) treatment induced high rates of
      complete response (CR), serious acute and late complications are frequent,
      whereas more vexatiously resistance to chemotherapy and clinical relapse
      develops. Therefore, the efficacy of treatment in Ph+ ALL is still to be
      determined. In this study, we focused our attention on the potential benefit of
      rapamycin (RAPA), an mammalian target of rapamycin (mTOR) inhibitor, in
      combination with IM on a Ph+ ALL cell line SUP-B15 and a primary Ph+ ALL sample
      in vitro. Analysis of cell proliferation showed that RAPA (50 nm) plus IM exerted
      good synergistic effect on Ph+ ALL cells. Notably, we found that IM treatment
      induced the abnormal activation of the components of mTOR signaling pathway and p
      BCR-ABL, whereas RAPA potently eliminated this deleterious side effect induced by
      IM and might overcome the resistance to IM. The synergistic effect was also
      associated with the increase in autophagy, which seemed to have an opposite role
      with apoptosis in Ph+ ALL cells, and cell cycle arrest in G1 phase. Altogether,
      our results suggested that IM in combination with RAPA was more effective for Ph+
      ALL cells than IM alone. 

PMID- 24112091
TI  - Chronic hepatitis C virus infection is associated with all-cause and liver
      related mortality in a cohort of HIV-infected patients with alcohol problems.
AB  - AIMS: To assess the association between hepatitis C virus (HCV) infection and
      overall and liver-related death in human immunodeficiency virus (HIV)-infected
      patients with alcohol problems. DESIGN: We analyzed data from a cohort of HIV
      infected adults with current or past alcohol problems enrolled between 2001 and
      2003, searching for causes of death until 2010 using the National Death Index.
      SETTING AND PARTICIPANTS: Participants were HIV-infected adults with current or
      past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals,
      homeless shelters, drug treatment programs, subject referrals, flyers and another
      cohort study with comparable recruitment sites. MEASUREMENTS: The primary and
      secondary outcomes were all-cause and liver-related mortality, respectively. The
      main independent variable was hepatitis C virus (HCV) RNA status (positive versus
      negative). Mortality rates and Kaplan-Meier survival curves were calculated by
      HCV status for both overall and liver-related mortality. Cox proportional hazards
      models were used to assess the association between HCV infection and overall and
      liver-related death, adjusting for alcohol and drug use over time. FINDINGS: A
      total of 397 adults (50% HCV-infected) were included. As of 31 December 2009, 83
      cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log-rank test P
      < 0.001), and 26 of those deaths were liver-related (21 HCV-infected, five HCV
      uninfected; log-rank test P < 0.001). All-cause and liver-related mortality rates
      were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65
      and 0.36 per 100 person-years for those without HCV, respectively. In the fully
      adjusted Cox model, HCV infection was associated with both overall [hazard ratio
      (HR) = 2.55, 95% confidence interval (CI) = 1.50-4.33, P < 0.01], and liver
      related mortality (HR = 3.24, 95% CI = 1.18-8.94, P = 0.02]. CONCLUSION:
      Hepatitis C virus infection is associated independently with all-cause and liver
      related mortality in human immunodeficiency virus-infected patients with alcohol
      problems, even when accounting for alcohol and other drug use.

PMID- 24112093
TI  - Changes in chemical composition and digestibility of three maize stover
      components digested by white-rot fungi.
AB  - Maize stover (total stem and leaves) is not considered a ruminant feed of high
      nutritive value. Therefore, an improvement in its digestibility may increase the
      viability of total forage maize production systems in marginal growth regions.
      The objective of this study was to describe the changes in chemical composition
      during the storage of contrasting components of maize stover (leaf, upper stem
      and lower stem) treated with either of two lignin degrading white-rot fungi (WRF;
      Pleurotus ostreatus, Trametes versicolor). Three components of maize stover
      (leaf, upper stem and lower stem), harvested at a conventional maturity for
      silage production, were digested with either of two WRF for one of four digestion
      durations (1-4 months). Samples taken prior to fungal inoculation were used to
      benchmark the changes that occurred. The degradation of acid detergent lignin was
      observed in all sample types digested with P. ostreatus; however, the loss of
      digestible substrate in all samples inoculated with P. ostreatus was high, and
      therefore, P. ostreatus-digested samples had a lower dry matter digestibility
      than samples prior to inoculation. Similarly, T. veriscolor-digested leaf
      underwent a non-selective degradation of the rumen-digestible components of
      fibre. The changes in chemical composition of leaf, upper stem and lower stem
      digested with either P. ostreatus or T. veriscolor were not beneficial to the
      feed value of the forage, and incurred high DM losses. 

PMID- 24112094
TI  - Sexual desire, erectile dysfunction and the biomedicalization of sex in older
      heterosexual men.
AB  - AIM: To examine sexual desire in older age and the use of pharmaceuticals for
      sexual enhancement in the context of erectile dysfunction. BACKGROUND: The
      ability of the older person to fulfil sexual desire has not been well supported
      in Western society. DESIGN: The paper draws on themes that emerged during a
      phenomenological study of sexual desire in older age. METHOD: Narratives were
      collected between 2008-2010 from in-depth interviews with six men and two women
      aged 65-84 years who were part of a larger Australian study of sexual desire in
      older age. FINDINGS: Emergent themes reveal that for some older people, the
      biomedicalization of sex can be a disappointing experience. CONCLUSION: The
      findings illuminate the need for nurses who are at the front line of health care,
      health policy makers and educators, to consider sexual desire experienced in
      older age in the context of sexual health and healthy ageing. This study will
      contribute to a growing body of knowledge about sexual desire in older age.

PMID- 24112097
TI  - Expression analysis of ovostatin 2 reveals its involvement in proliferation,
      invasion and angiogenesis of cutaneous malignant melanoma.
AB  - The relationship of ovostatin 2 (OVOS2) expression with the clinicopathological
      features of cutaneous malignant melanoma (CMM) was investigated to identify OVOS2
      expression in cutaneous melanocytic lesions, and to reveal whether OVOS2 has a
      function in melanoma progression. Eight specimens of CMM and paracancerous tissue
      were analyzed using real-time polymerase chain reaction (PCR) and western blot
      for the mRNA and protein expression of OVOS2, respectively. Immunohistochemical
      staining was performed on 52 CMM and 62 nevi, followed by clinicopathological
      significance analysis. The proliferative cells were visualized by staining with
      Ki-67 antibody. The intensity of angiogenesis was assessed by staining with
      vascular endothelial growth factor (VEGF). Real-time PCR and western blot
      analyses showed that OVOS2 was significantly upregulated in cutaneous melanoma
      than in paired normal skins. Immunohistochemistry showed that 86.5% (45/52) of
      malignant cases showed OVOS2 cytoplasmic expression compared with 29% (18/62) in
      benign nevi. OVOS2 expression was significantly higher in invasive and metastatic
      melanoma than in in situ melanoma (P < 0.01). Furthermore, OVOS2 expression was
      positively correlated with the known prognostic variables of melanoma including
      clinical stage, Clark level and Breslow depth. It was also significantly
      associated with ulcer status, Ki-67 labeling index and VEGF expression in primary
      melanoma. OVOS2 expression was significantly increased in CMM, which increased
      incrementally from benign nevi to melanoma and appeared to be involved in the
      progression of melanoma.

PMID- 24112095
TI  - Adenine-DNA adduct derived from the nitroreduction of 6-nitrochrysene is more
      resistant to nucleotide excision repair than guanine-DNA adducts.
AB  - Previous studies in rats, mice, and in vitro systems showed that 6-NC can be
      metabolically activated by two major pathways: (1) the formation of N-hydroxy-6
      aminochrysene by nitroreduction to yield three major adducts, N-(dG-8-yl)-6-AC, 5
      (dG-N(2)-yl)-6-AC, and N-(dA-8-yl)-6-AC, and (2) the formation of trans-1,2
      dihydroxy-1,2-dihydro-6-hydroxylaminochrysene (1,2-DHD-6-NHOH-C) by a combination
      of nitroreduction and ring oxidation pathways to yield N-(dG-8-yl)-1,2-DHD-6-AC,
      5-(dG-N(2)-yl)-1,2-DHD-6-AC and N-(dA-8-yl)-1,2-DHD-6-AC. These DNA lesions are
      likely to cause mutations if they are not removed by cellular defense mechanisms
      before DNA replication occurs. Here, we compared for the first time, in HeLa cell
      extracts in vitro, the relative nucleotide excision repair (NER) efficiencies of
      DNA lesions derived from simple nitroreduction and from a combination of
      nitroreduction and ring oxidation pathways. We show that the N-(dG-8-yl)-1,2-DHD
      6-AC adduct is more resistant to NER than the N-(dG-8-yl)-6-AC adduct by a factor
      of ~2. Furthermore, the N-(dA-8-yl)-6-AC is much more resistant to repair since
      its NER efficiency is ~8-fold lower than that of the N-(dG-8-yl)-6-AC adduct. On
      the basis of our previous study and the present investigation, lesions derived
      from 6-NC and benzo[a]pyrene can be ranked from the most to the least resistant
      lesion as follows: N-(dA-8-yl)-6-AC > N-(dG-8-yl)-1,2-DHD-6-AC > 5-(dG-N(2)-yl)-6
      AC ? N-(dG-8-yl)-6-AC ? (+)-7R,8S,9S,10S-benzo[a]pyrene diol epoxide-derived
      trans-anti-benzo[a]pyrene-N(2)-dG adduct. The slow repair of the various lesions
      derived from 6-NC and thus their potential persistence in mammalian tissue could
      in part account for the powerful carcinogenicity of 6-NC as compared to B[a]P in
      the rat mammary gland. 

PMID- 24112096
TI  - The relationship between primary prescription opioid and buprenorphine-naloxone
      induction outcomes in a prescription opioid dependent sample.
AB  - BACKGROUND AND OBJECTIVES: This analysis aims to: (1) compare induction
      experiences among participants who self-reported using one of the four most
      commonly reported POs, and (2) examine factors associated with difficult bup-nx
      induction. Our hypothesis, based on previous research and current guidelines, is
      that those on longer-acting opioids will have experienced more difficult
      inductions. METHODS: The Prescription Opioid Addiction Treatment Study (POATS)
      was a multi-site, randomized clinical trial, using a two-phase adaptive treatment
      research design. This analysis examines bup-nx induction of participants who self
      reported primary PO use of methadone, ER-oxycodone, IR-oxycodone, and hydrocodone
      (n = 69). Analyses examined characteristics associated with difficult induction,
      defined as increased withdrawal symptoms measured by the Clinical Opiate
      Withdrawal Scale (COWS) after the first bup-nx dose with higher scores denoting
      greater withdrawal symptoms/severity. RESULTS: Contrary to our hypothesis,
      difficult induction experiences did not differ by primary PO type. Those who
      experienced a post-induction increase in COWS score had lower pre-dose COWS
      scores compared to those who did not experience a post-induction increase in COWS
      score (10.09 vs. 12.77, t(624) = -13.56, p < .001). Demographics characteristics,
      depression, and pain history did not predict a difficult induction. CONCLUSIONS
      AND SCIENTIFIC SIGNIFICANCE: Difficult bup-nx inductions were not associated with
      participants' primary PO. Severity of withdrawal, measured with the COWS, was an
      important variable, reminding clinicians that bup-nx should not be commenced
      prior to evidence of moderate opioid withdrawal. These findings add to the
      evidence that with careful procedures, bup-nx can used with few difficulties in
      PO-dependent patients. (Am J Addict 2014;23:343-348).

PMID- 24112098
TI  - Simvastatin induces the osteogenic differentiation of human periodontal ligament
      stem cells.
AB  - Periodontal ligament stem cells (PDLSCs) are considered as potential mesenchymal
      stem cell sources for future clinical applications in periodontal regeneration
      therapy. Simvastation, widely used for lowering serum cholesterol, is known to
      have a bone stimulatory effect. However, it is not clear whether simvastation
      affects the differentiation of PDLSCs. This study examined the effects of
      simvastatin on human PDLSCs in vitro and in vivo. Using the limiting dilution
      technique, human PDLSCs were isolated and expanded. PDLSCs were cultured with
      simvastatin (0.01-10 MUM), and the proliferation was measured. The osteogenic
      differentiation was characterized by alkaline phosphatase (ALP) activity and
      Alizarin Red-S staining for calcium deposition. The gene expression levels of
      osteogenic markers were evaluated by RT-PCR. In addition, PDLSCs were
      transplanted into nude mice with ceramic bovine bone powders as carriers to
      observe the capacity of mineralized tissue formation in vivo. Simvastatin at
      concentrations <1 MUM did not suppress the proliferation of PDLSCs. After the
      administration of 0.1 MUM simvastatin, the expression of ALP, bone sialoprotein,
      and bone morphogenetic protein-2 genes were significantly upregulated, and the
      ALP activity and mineralized nodule formation were significantly higher in the
      simvastatin-treated cells than the control cells. In addition, the in vivo
      transplantation results showed that simvastatin treatment promoted the degree of
      mineralized tissue formation. Collectively, simvastatin has positive effects on
      osteogenic differentiation of human PDLSCs in vitro and in vivo. This suggests
      that simvastatin might be a useful osteogenic induction agent for periodontal
      bone regeneration.

PMID- 24112100
TI  - Acute schistosomiasis in European students returning from fieldwork at Lake
      Tanganyika, Tanzania.
AB  - BACKGROUND: Schistosomiasis is common in many African regions and poses a risk
      for travelers and the local population. So far, schistosomiasis in travelers or
      expatriates returning from the Tanzanian bank of Lake Tanganyika has not been
      reported. METHODS: We report a group of students who sought treatment with signs
      of acute schistosomiasis after having returned from Lake Tanganyika, Tanzania.
      Information as to travel and exposure as well as clinical and laboratory data
      were collected. RESULTS: Schistosomiasis was diagnosed in 8 of 16 students from
      Berlin, Germany, who had returned from a 2- to 3-month stay of fieldwork in
      Kigoma District at Lake Tanganyika, Tanzania. All 16 students reported frequent
      freshwater exposure at the lake. Six patients showed signs of acute
      schistosomiasis and had fever, and some of them also had cough, weakness,
      headache, or abdominal pain. Eosinophilia was present in five of the six
      symptomatic individuals. Notably, two serologically enzyme-linked immunosorbent
      assay (ELISA)-positive individuals did not report or present with symptoms or
      abnormal laboratory parameters. Schistosoma mansoni eggs were found in one
      symptomatic and one asymptomatic individual each. Blood and stool samples from
      the other eight individuals who were equally exposed to freshwater yielded
      negative results. CONCLUSIONS: This is the first report of an outbreak of acute
      schistosomiasis imported from the Tanzanian shore of Lake Tanganyika and
      highlights the risk for travelers and the local population of acquiring the
      infection in that part of Tanzania. It provides arguments for routine serological
      screening for schistosomiasis in individuals who had prior freshwater contact in
      endemic areas, irrespective of symptoms or other laboratory findings.

PMID- 24112099
TI  - Development of exchange lists for Mediterranean and Healthy Eating diets:
      implementation in an intervention trial.
AB  - BACKGROUND: There has been little research published on the adaptation of
      diabetic exchange list diet approaches for the design of intervention diets in
      health research despite their clinical utility. The exchange list approach can
      provide clear and precise guidance on multiple dietary changes simultaneously.
      The present study aimed to develop exchange list diets for Mediterranean and
      Healthy Eating, and to evaluate adherence, dietary intakes and markers of health
      risks with each counselling approach in 120 subjects at increased risk for
      developing colon cancer. METHODS: A randomised clinical trial was implemented in
      the USA involving telephone counselling. The Mediterranean diet had 10 dietary
      goals targeting increases in mono-unsaturated fats, n-3 fats, whole grains and
      the amount and variety of fruits and vegetables. The Healthy Eating diet had five
      dietary goals that were based on the US Healthy People 2010 recommendations.
      RESULTS: Dietary compliance was similar in both diet arms, with 82-88% of goals
      being met at 6 months, although subjects took more time to achieve the
      Mediterranean goals than the Healthy Eating goals. The relatively modest fruit
      and vegetable goals in the Healthy Eating arm were exceeded, resulting in fruit
      and vegetable intakes of approximately eight servings per day in each arm after 6
      months. A significant (P < 0.05) weight loss and a decrease in serum C-reactive
      protein concentrations were observed in the overweight/obese subgroup of subjects
      in the Mediterranean arm in the absence of weight loss goals. CONCLUSIONS:
      Counselling for the Mediterranean diet may be useful for both improving diet
      quality and for achieving a modest weight loss in overweight or obese
      individuals.

PMID- 24112101
TI  - Therapeutic role of EF24 targeting glucose transporter 1-mediated metabolism and
      metastasis in ovarian cancer cells.
AB  - Cancer cells require glucose to support their rapid growth through a process
      known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells,
      increased metabolic activity and glucose concentration has been linked to
      aggressiveness of cancer. However, it is unclear as to whether targeting the
      glycolytic pathway may kill the malignant cells and likely have broad therapeutic
      implications against ovarian cancer metastasis. In the present research, we found
      that EF24, a HIF-1alpha inhibitor, could significantly block glucose uptake, the
      rate of glycolysis, and lactate production compared with vehicle treatment in
      SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the
      further observation that EF24 could inhibit ovarian cancer cell migration and
      invasion from wound healing and Transwell assays. Furthermore, as an important
      mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to
      contribute to the function of EF24 in both energy metabolism and metastasis. To
      examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph
      subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model
      were introduced. Our results indicated that EF24 treatment could inhibit tumor
      growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1
      is a possible mediator for the role of EF24. In conclusion, our results highlight
      that an anti-cancer reagent with an inhibiting effect on energy metabolism could
      inhibit metastasis, and EF24 is a possible candidate for anti-metastasis
      therapeutic applications for ovarian cancer.

PMID- 24112102
TI  - Eosinophil major basic protein activates human cord blood mast cells primed with
      fibroblast membranes by integrin-beta1.
AB  - BACKGROUND: Mast cell (MC) - eosinophil (Eos) activating cross-talk might be
      critical for the severity and chronicity of allergy. Among soluble mediators,
      eosinophil major basic protein (MBP), a hallmark of allergy, is particularly
      important because it was shown to activate specific MC subtypes. We previously
      demonstrated that MBP activates IgE-desensitized rat MC and human lung and cord
      blood-derived MC (CBMC) after priming with fibroblast membranal stem cell factor.
      However, a distinct mechanism for this activation was missing. Therefore, we
      aimed to investigate it. METHODS: Major basic protein-1 activation of CBMC primed
      with fibroblast-derived membranes (FBM) was measured by beta-hexosaminidase and
      tryptase release. Chemical cross-linking followed by micrometric flow cytometry
      probed direct interactions. Antibodies neutralized integrin-beta1 and recognized
      its active form. Pertussis toxin (Ptx) was used to decrease integrin-beta1 active
      form expression. Hematopoietic cell kinase (Hck) was identified by
      immunoprecipitation (IP) and silenced by siRNA. RESULTS: Major basic protein-1
      induced CBMC activation is mediated partly by MBP1-integrin-beta1 interaction on
      the MC surface. FBM prime CBMC via a G protein, as confirmed by Ptx, to shift
      integrin-beta1 to its active form. Following MBP1 binding, integrin-beta1 binds
      Hck that further transduces the activation signal. MC priming with FBM leads to
      up-regulation in Hck protein level. MC integrin-beta1 neutralization inhibits
      MBP1-induced activation and uptake. Hck silencing results with reduced MBP1
      induced activation. CONCLUSIONS: Fibroblast-derived membranes, integrin-beta1,
      and Hck are involved in MBP1-induced activation of CBMC and therefore represent a
      distinct mechanism for this activation. This finding might implicate integrin
      beta1 and Hck as targets for decreasing MC - Eos activating cross-talk in
      allergy.

PMID- 24112103
TI  - TP53 mutation and human papilloma virus status of oral squamous cell carcinomas
      in young adult patients.
AB  - OBJECTIVE: Little is known about the molecular carcinogenesis of oral squamous
      cell carcinoma (OSCC) in young adult patients. The aim of this study was to
      investigate the detailed TP53 mutation and human papilloma virus (HPV) status of
      OSCC in patients, younger than 45 years. METHODS: TP53 mutations were determined
      with direct sequencing on paraffin-embedded carcinoma tissue from 31 young
      patients and compared with two older age OSCC reference groups: one from the same
      institute (N = 87) and an independent one (N = 675). Biologically active tumour
      HPV was detected by p16-immunohistochemistry followed by a HPV-DNA GP5 + /6 + 
      PCR. RESULTS: HPV16 was present in one OSCC (3%). TP53 mutations were found in 14
      (45%) OSCC: five were missense and nine resulted in a truncated protein. Six of
      these latter were insertions or deletions of one or more nucleotides leading to
      frameshift, one was at a splice site and two resulted in a stop codon. The
      percentage of truncating mutations (64% of all mutations) was higher than that
      observed in the institute's reference group (44%, P = 0.23) and in the
      independent reference group (24%, P = 0.002). CONCLUSIONS: This study shows that
      TP53 mutations are common in OSCC of young adult patients; infection with
      biologically active HPV is rare.

PMID- 24112105
TI  - Benefits of investing in ecosystem restoration.
AB  - Measures aimed at conservation or restoration of ecosystems are often seen as net
      cost projects by governments and businesses because they are based on incomplete
      and often faulty cost-benefit analyses. After screening over 200 studies, we
      examined the costs (94 studies) and benefits (225 studies) of ecosystem
      restoration projects that had sufficient reliable data in 9 different biomes
      ranging from coral reefs to tropical forests. Costs included capital investment
      and maintenance of the restoration project, and benefits were based on the
      monetary value of the total bundle of ecosystem services provided by the restored
      ecosystem. Assuming restoration is always imperfect and benefits attain only 75%
      of the maximum value of the reference systems over 20 years, we calculated the
      net present value at the social discount rates of 2% and 8%. We also conducted 2
      threshold cum sensitivity analyses. Benefit-cost ratios ranged from about 0.05:1
      (coral reefs and coastal systems, worst-case scenario) to as much as 35:1
      (grasslands, best-case scenario). Our results provide only partial estimates of
      benefits at one point in time and reflect the lower limit of the welfare benefits
      of ecosystem restoration because both scarcity of and demand for ecosystem
      services is increasing and new benefits of natural ecosystems and biological
      diversity are being discovered. Nonetheless, when accounting for even the
      incomplete range of known benefits through the use of static estimates that fail
      to capture rising values, the majority of the restoration projects we analyzed
      provided net benefits and should be considered not only as profitable but also as
      high-yielding investments. Beneficios de Invertir en la Restauracion de
      Ecosistemas. 

PMID- 24112104
TI  - Clinicopathological findings in non-human primate recipients of porcine renal
      xenografts: quantitative and qualitative evaluation of proteinuria.
AB  - BACKGROUND: Immunological and histopathological features in pig-to-primate renal
      xenotransplantation are widely studied. Only limited data have been reported
      about clinicopathological findings in primate recipients of life-supporting renal
      xenografts. In human medicine, proteinuria represents a common complication in
      kidney transplantation and is associated with impaired graft survival. The
      detection of low molecular weight proteins of tubular origin is considered an
      early method for predicting potential graft rejection. In this study, the
      presence and the significance of quantitative and qualitative proteinuria were
      evaluated in xenotransplanted non-human primates in which kidney function was
      supported only by the transplanted organ. METHODS: Eight bilaterally
      nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a
      single kidney from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs
      transgenic for human CD39, CD55, CD59, and alpha1,2-fucosyltransferase. In
      addition to hematological and biochemical analyses, quantitative and qualitative
      analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC
      ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE),
      respectively. RESULTS: The main hematological and biochemical changes recorded
      after transplantation were a progressive anemia and a severe and progressive
      decrease in total proteins. In urine samples, the UPC ratio was low before
      transplantation and increased after transplantation. Similarly, SDS-AGE was
      negative before transplantation, but bands consistent with mixed (i.e., tubular
      and glomerular) proteinuria were observed in all samples collected post
      transplantation. CONCLUSIONS: The study of clinicopathological changes in
      cynomolgus monkey renal xenograft recipients provides a valid help in monitoring
      the health conditions in the post-transplant period. Moreover, the evaluation of
      UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey
      renal xenograft recipients may be considered a valid, inexpensive, and less time
      consuming method than more sophisticated techniques in monitoring proteinuria.
      Proteinuria and presence of low molecular weight (LMW) proteins were consistently
      found in urine after transplantation, independent of fluctuations in renal
      function.

PMID- 24112106
TI  - Eotaxin-1 is involved in parasite clearance during chronic filarial infection.
AB  - Eosinophil migration as key feature of helminth infection is increased during
      infection with filarial nematodes. In a mouse model of filariasis, we
      investigated the role of the eosinophil-attracting chemokine Eotaxin-1 on disease
      outcome. BALB/c and Eotaxin-1(-/-) mice were infected with the rodent filaria
      Litomosoides sigmodontis, and parasitic parameters, cellular migration to the
      site of infection, and cellular responsiveness were investigated. We found
      increased parasite survival but unaffected eosinophil migration to the site of
      infection in Eotaxin-1(-/-) mice. Expression of CD80 and CD86 was reduced on
      eosinophils from Eotaxin-1(-/-) mice after in vitro TLR2 stimulation and exposure
      to filarial antigen, respectively, suggesting a potential reduced activation
      state of eosinophils in Eotaxin-1 deficient mice. We further demonstrated that
      macrophages from Eotaxin-1(-/-) mice produce decreased amounts of IL-6 in vitro,
      a cytokine found to be associated with parasite containment, suggesting possible
      mechanisms by which Eotaxin-1 regulates activation of inflammatory cells and thus
      parasite survival. 

PMID- 24112107
TI  - Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone
      (New Zealand black/New Zealand white) F1 mice.
AB  - The safety of four different adjuvants was assessed in lupus-prone New Zealand
      black/New Zealand white (BW)F1 mice. Four groups of mice were injected
      intraperitoneally with incomplete Freund's adjuvant (IFA), complete Freund's
      adjuvant (CFA), squalene (SQU) or aluminium hydroxide (ALU). An additional group
      received plain phosphate-buffered saline (PBS) (UNT group). Mice were primed at
      week 9 and boosted every other week up to week 15. Proteinuria became detectable
      at weeks 17 (IFA group), 24 (CFA group), 28 (SQU and ALU groups) and 32 (UNT
      group). Different mean values were obtained among the groups from weeks 17 to 21
      [week 17: one-way analysis of variance (anova) P = 0.016; weeks 18 and 19: P =
      0.048; weeks 20 and 21: P = 0.013] being higher in the IFA group than the others
      [Tukey's honestly significant difference (HSD) post-test P < 0.05]. No
      differences in anti-DNA antibody levels were observed among groups. Anti-RNP/Sm
      antibody developed at week 19 in only one CFA-treated mouse. Mean mouse weight at
      week 18 was lower in the ALU group than the IFA (Tukey's HSD post-test P = 0.04),
      CFA (P = 0.01) and SQU (P < 0.0001) groups, while the mean weight in the SQU
      group was higher than in the IFA (P = 0.009), CFA (P = 0.013) and UNT (P = 0.005)
      groups. The ALU group weight decreased by almost half between weeks 29 and 31,
      indicating some toxic effect of ALU in the late post-immunization period. Thus,
      SQU was the least toxic adjuvant as it did not (i) accelerate proteinuria onset
      compared to IFA; (ii) induce toxicity compared to ALU or (iii) elicit anti-RNP/Sm
      autoantibody, as occurred in the CFA group.

PMID- 24112108
TI  - Rates and risk of hospitalisation among patients with type 2 diabetes:
      retrospective cohort study using the UK General Practice Research Database linked
      to English Hospital Episode Statistics.
AB  - AIMS: To investigate the rates and risk of hospitalisations in patients with type
      2 diabetes (T2D) mellitus in England. METHODS: This retrospective population
      based cohort study used computerised records from the General Practice Research
      Database linked to Hospital Episode Statistics data in England. Patients with T2D
      from January 2006 to December 2010 were selected. Primary outcome measures were
      all-cause, non-diabetes-related, diabetes-related and hypoglycaemia-related
      hospitalisations. Factors associated with all-cause and diabetes-related
      hospitalisations were investigated with Cox's proportional hazards models.
      RESULTS: Amongst 97,689 patients with T2D, approximately 60% had at least one
      hospitalisation during the 4-year study period. Rates of hospitalisation were as
      follows: all-cause, 33.9 per 100 patient-years (pt-yrs); non-diabetes-related,
      29.1 per 100 pt-yrs; diabetes-related, 18.8 per 100 pt-yrs and hypoglycaemia, 0.3
      per 100 pt-yrs. The risk of all-cause hospitalisation increased with
      hospitalisation in the previous year, insulin use and the presence of major
      comorbidities. The risk of a diabetes-related hospitalisation increased with age,
      female gender, insulin use, chronic renal insufficiency, hypoglycaemia (as
      diagnosed by a general practitioner) and diabetes-related hospitalisation in the
      previous year. CONCLUSIONS: Patients with T2D are hospitalised at a considerably
      high rate for causes directly related with diabetes complications and stay longer
      in hospital. History of hospitalisation and complications of diabetes were found
      to be predictive of inpatient hospitalisations suggesting previous
      hospitalisation episodes could serve as points of intervention. This study
      highlights important areas for healthcare intervention and provides a reminder
      for vigilance when risk factors for hospitalisation in patients with T2D are
      present.

PMID- 24112109
TI  - A LOV-domain-mediated blue-light-activated adenylate (adenylyl) cyclase from the
      cyanobacterium Microcoleus chthonoplastes PCC 7420.
AB  - Genome screening of the cyanobacterium Microcoleus chthonoplastes PCC 7420
      identified a gene encoding a protein (483 amino acids, 54.2 kDa in size)
      characteristic of a BL (blue light)-regulated adenylate (adenylyl) cyclase
      function. The photoreceptive part showed signatures of a LOV (light, oxygen,
      voltage) domain. The gene product, mPAC (Microcoleus photoactivated adenylate
      cyclase), exhibited the LOV-specific three-peaked absorption band (lambdamax=450
      nm) and underwent conversion into the photoadduct form (lambdamax=390 nm) upon BL
      irradiation. The lifetime for thermal recovery into the parent state was
      determined as 16 s at 20 degrees C (25 s at 11 degrees C). The adenylate cyclase
      function showed a constitutive activity (in the dark) that was in-vitro-amplified
      by a factor of 30 under BL-irradiation. Turnover of the purified protein at
      saturating light and pH 8 is estimated to 1 cAMP/mPAC per s at 25 degrees C (2
      cAMP/mPAC per s at 35 degrees C). The lifetime of light-activated cAMP production
      after a BL flash was ~14 s at 20 degrees C. The temperature optimum was
      determined to 35 degrees C and the pH optimum to 8.0. The value for half-maximal
      activating light intensity is 6 W/m2 (at 35 degrees C). A comparison of mPAC and
      the BLUF (BL using FAD) protein bPAC (Beggiatoa PAC), as purified proteins and
      expressed in Xenopus laevis oocytes, yielded higher constitutive activity for
      mPAC in the dark, but also when illuminated with BL. 

PMID- 24112110
TI  - Emerald ash borer invasion of North America: history, biology, ecology, impacts,
      and management.
AB  - Since its accidental introduction from Asia, emerald ash borer (EAB), Agrilus
      planipennis Fairmaire (Coleoptera: Buprestidae), has killed millions of ash trees
      in North America. As it continues to spread, it could functionally extirpate ash
      with devastating economic and ecological impacts. Little was known about EAB when
      it was first discovered in North America in 2002, but substantial advances in
      understanding of EAB biology, ecology, and management have occurred since. Ash
      species indigenous to China are generally resistant to EAB and may eventually
      provide resistance genes for introgression into North American species. EAB is
      characterized by stratified dispersal resulting from natural and human-assisted
      spread, and substantial effort has been devoted to the development of survey
      methods. Early eradication efforts were abandoned largely because of the
      difficulty of detecting and delineating infestations. Current management is
      focused on biological control, insecticide protection of high-value trees, and
      integrated efforts to slow ash mortality. 

PMID- 24112111
TI  - Nancy E. Beckage (1950-2012): pioneer in insect host-parasite interactions.
AB  - Nancy E. Beckage is widely recognized for her pioneering work in the field of
      insect host-parasitoid interactions beginning with endocrine influences of the
      tobacco hornworm, Manduca sexta, host and its parasitoid wasp Apanteles
      congregatus (now Cotesia congregata) on each other's development. Moreover, her
      studies show that the polydnavirus carried by the parasitoid wasp not only
      protects the parasitoid from the host's immune defenses, but also is responsible
      for some of the developmental effects of parasitism. Nancy was a highly regarded
      mentor of both undergraduate and graduate students and more widely of women
      students and colleagues in entomology. Her service both to her particular area
      and to entomology in general through participation on federal grant review panels
      and in the governance of the Entomological Society of America, organization of
      symposia at both national and international meetings, and editorship of several
      different journal issues and of several books is legendary. She has left behind a
      lasting legacy of increased understanding of multilevel endocrine and
      physiological interactions among insects and other organisms and a strong network
      of interacting scientists and colleagues in her area of entomology. 

PMID- 24112112
TI  - Radical-based epoxide opening by titanocenes.
AB  - The binding of 2,2-diphenyloxirane to Cp2TiCl is studied on the electronic level
      by magnetic resonance spectroscopy and quantum chemical calculations. The
      complexation of 2,2-diphenyloxirane is accompanied by dissociation of the
      chloride ligand, and thus, the epoxide binds to the cationic titanocene(III)
      complex. The titanocene(III)-epoxide species persists only for short periods of
      time (<5 min) even at 243 K, indicating that the ring-opening reaction is
      exothermic. A short-lived paramagnetic titanocene(IV)-epoxide radical species has
      not been directly observed. However, by a combination of isotope labeling and
      spin-trapping, evidence for the existence of such a species has been
      unequivocally demonstrated. The observation of a titanocene(III)-epoxide complex
      is unprecedented and provides direct evidence for inner-sphere electron transfer
      between epoxides and titanocenes, responsible for the high regioselectivity of
      ring-opening. 

PMID- 24112113
TI  - Hypersexual behavior and HIV sex risk among young gay and bisexual men.
AB  - Hypersexual behavior has been identified as a sexual risk correlate among gay and
      bisexual men (GBM). The Hypersexual Behavior Inventory (HBI) has been shown to be
      a reliable and valid measure of hypersexual behavior in clinical populations, yet
      it has not been used to assess hypersexual behavior in nonclinical samples. We
      examined the psychometric properties of the HBI with survey data recorded between
      December 2009 and March 2010 in a sample of young men (N = 366, M = 21.46 years
      old, SD = 1.95) who self-identified as gay (89%) or bisexual (11%) and assessed
      its association with unprotected receptive anal intercourse (URAI) partners and
      occasions. Using cross-sectional data of single, sexually active young GBM
      (YGBM), we used confirmatory factor analyses to test the HBI's three-factor
      structure. Using negative binomial regressions, we then tested the association
      between the HBI subscales and sexual risk. After accounting for covariates, we
      found that sexual control was a risk factor for URAI partners and occasions, and
      coping was found to be a protective factor for URAI occasions. In light of our
      findings, we discuss the importance of reexamining the theoretical assumptions of
      hypersexual behavior and propose HIV prevention strategies that may reduce young
      GBM's vulnerability to HIV infection. 

PMID- 24112114
TI  - Chediak-Higashi syndrome: description of two novel homozygous missense mutations
      causing divergent clinical phenotype.
AB  - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease resulting
      from mutations in the LYST/CHS1 gene, which encodes for a 429 kDa protein,
      CHS1/LYST, that regulates vesicle trafficking and determines the size of
      lysosomes and other organelles. To date, 60 different mutations have been
      characterized, and a reasonably straightforward phenotype-genotype correlation
      has been suggested. We describe two patients on opposite ends of the CHS clinical
      spectrum with novel missense mutations. We characterized these patients in terms
      of their mutations, protein localization and expression, mRNA stability, and
      electrostatic potential. Patient 1 is the first report of a severe early-onset
      CHS with a homozygous missense mutation (c.11362 G>A, p.G3725R) in the LYST/CHS1
      gene. This molecular change results in a reduction at the CHS1 protein level, not
      due to an mRNA effect, but maybe a consequence of both, a change in the structure
      of the protein and most likely attributable to the remarkable serious
      perturbation in the electrostatic potential. Patient 2, who exhibited the
      adolescence form of the disease, was found to be homozygous for a novel missense
      mutation c.961 T>C, p.C258R, which seemed to have minor effect on the structure
      of the CHS1/LYST protein. Reexamining accepted premises of missense mutant
      alleles being reported among patients with clinically mild forms of the disorder
      should be carried out, and attempts to link genotype and clinical phenotype
      require identifying the actual molecular effect of the mutation. Early and
      accurate diagnosis of the severity of the disease is extremely important to early
      differentiate patients who would benefit from premature enrollment into a
      transplantation protocol. 

PMID- 24112115
TI  - Pressure ulcer in patients with severe traumatic brain injury: significant
      factors and association with neurological outcome.
AB  - AIMS AND OBJECTIVES: To assess the factors associated with development of
      pressure ulcer in patients with severe traumatic brain injury (TBI) and study its
      prognostic significance with respect to neurological outcome at three months.
      BACKGROUND: Patients with severe TBI are prone to develop pressure ulcer due to
      various factors, which have never been studied in detail. DESIGN: Prospective
      longitudinal study. METHODS: Eighty-nine patients of TBI in age group 20-60 years
      admitted with Glasgow Coma Scale (GCS) 4-8 without serious systemic disorder were
      enrolled for the study. Patient characteristics, haemoglobin, serum albumin
      levels at admission and their weekly changes till 21 days were noted along with
      daily assessment for presence of pressure ulcer. Mortality was assessed at 21
      days and neurological outcome at three months through telephonic interview.
      RESULTS: Of 89 patients studied, pressure ulcer was observed in 6 (7%) and 14
      (16%) at the end of two and three weeks, respectively. Pressure ulcer in
      univariate analysis was significantly associated with poorer GCS (p = 0.05),
      delayed enteral feeding (p = 0.005) and fall in haemoglobin at two weeks (p =
      0.005). Only the latter two were found significant in multivariate analysis. Age,
      gender, surgical intervention, tracheostomy, prolonged fever and change in
      albumin had no significant association with pressure ulcer development. Presence
      of pressure ulcer was significantly associated with mortality at 21 days (p =
      0.006) and unfavourable neurological outcome at three months (p = 0.01).
      CONCLUSIONS: The significant factors influencing pressure ulcer development in
      patients with TBI were delayed enteral feeding and fall in haemoglobin. Pressure
      ulcer had significant association with mortality at 21 days and recovery status
      at three months. RELEVANCE TO CLINICAL PRACTICE: Early nutritional
      supplementation and monitoring of haemoglobin should be an important part of
      nursing care interventions for patients at increased risk of developing pressure
      ulcer.

PMID- 24112116
TI  - Reversal strategy in antagonizing the P2Y12 -inhibitor ticagrelor.
AB  - BACKGROUND: Patients on antiplatelet therapy have a higher incidence of bleeding
      complications. Reversal of antiplatelet drug effects is an important issue at
      trauma or emergency departments. For old and conventional anticoagulants,
      reversal strategies are established. While the effects of ticagrelor are
      reversible, developing a method to restore platelet function in patients is of
      importance due to its longer half-life (approximately 8 h), compared with other
      P2Y12 -inhibitors. MATERIALS AND METHODS: We report an ex vivo model to reverse
      the effects of the novel and highly effective P2Y12 -inhibitor ticagrelor in 20
      healthy volunteers. To normalize platelet reactivity, we added increasing amounts
      of autologous platelet-rich plasma (PRP) to whole blood which was obtained 3 h
      after the intake of 180 mg of ticagrelor. Platelet aggregation was assessed by
      whole blood multiple electrode aggregometry (MEA), which is based on impedance
      aggregometry. RESULTS: The basal ADP-induced platelet aggregation averaged 71 +/-
      16 U (Units). Ticagrelor decreased ADP-induced platelet aggregation to 16 +/- 8
      U. A clear dose-response was obtained after spiking whole blood with increasing
      amounts of PRP. It is estimated that >=2 units of apheresis platelet concentrates
      will be necessary to completely restore baseline platelet aggregation in the
      majority of patients after ticagrelor. CONCLUSIONS: Platelets dose dependently
      improve ex vivo platelet aggregation of subjects after a loading dose of 180 mg
      of ticagrelor, making transfusion of platelet concentrates potentially useful in
      bleeding patients and those who need to undergo emergency surgery.

PMID- 24112117
TI  - Reconciling recovery, personalisation and Housing First: integrating practice and
      outcome in the field of multiple exclusion homelessness.
AB  - 'Recovery' is a key concept in the organisation and delivery of interdisciplinary
      support for people experiencing multiple exclusion homelessness (MEH, that is,
      situations where homelessness overlaps with a range of other complex problems
      such as mental health issues and drug and alcohol dependencies). At the level of
      individual support planning, practitioners are expected to 'work together' to
      motivate service users to make positive changes to their lives and to secure
      outcomes (results) such as employment and permanent accommodation. Drawing on the
      accounts of 34 (n = 34) people with first-hand experience of MEH in England, we
      outline some of the limitations of 'recovery-orientated practices', namely the
      exclusion of people with unresolved needs and the implications this may have for
      continuity of provision. To address this issue, we argue that there is a need for
      a more personalised and inclusive practice model, which can accommodate
      'recovery' (change outcomes) alongside those for maintenance and prevention. In
      proposing one such model, we show how this might also take forward the principles
      of 'Housing First' (a US blueprint for tackling entrenched homelessness), which
      has already begun to challenge the orthodox view that permanent accommodation
      should be provided only when recovery has been achieved.

PMID- 24112118
TI  - Racial/ethnic differences in report of drug testing practices at the workplace
      level in the U.S.
AB  - BACKGROUND AND OBJECTIVES: It is unknown whether racial/ethnic differences in
      report of workplace drug testing persist when analyzed within and across various
      occupations. We sought to examine the association between worker demographics,
      workplace characteristics, and report of employment in a workplace that performs
      drug testing. METHODS: We performed a cross-sectional study of the 2008-2010
      National Survey on Drug Use and Health examining the relationship between
      race/ethnicity and report of workplace drug testing among employed, white, black,
      or Hispanic respondents >=18 years old. In logistic regression analysis, we
      adjusted for demographic, occupational, and other relevant variables and
      performed stratified analyses among three specific occupations. RESULTS: Among
      69,163 respondents, 48.2% reported employment in a workplace that performs drug
      testing. On multivariable analysis, younger age, male sex, black race, income
      greater than $20,000, completion of high school and non-urban residence were
      associated with report of drug testing at one's workplace among the full sample
      as were non-white collar occupation, work in medium or large workplace, and
      absence of other substance abuse/dependence. In stratified analyses, black race
      was associated with report of workplace level drug testing among
      executive/administrative/managerial/financial workers and technicians/related
      support occupations; Hispanic ethnicity was associated with the outcome among
      technicians/related support occupations. CONCLUSIONS: Racial/ethnic differences
      in report of workplace drug testing exist within and across various occupations.
      These differences have important public health implications deserving further
      study. SCIENTIFIC SIGNIFICANCE: Increased report of drug testing where
      racial/ethnic minorities work highlights the potential bias that can be
      introduced when drug testing policies are not implemented in a universal fashion.

PMID- 24112120
TI  - Six-month trajectory of suicidal ideation in adolescents with borderline
      personality disorder.
AB  - Few studies have longitudinally examined suicidal ideation in those with
      adolescent-onset borderline personality disorder (BPD). The current study aimed
      to examine the trajectory of suicidal ideation in adolescents with BPD
      longitudinally over 6 months, with follow-ups at 2, 4, and 6 months
      posthospitalization for elevated suicide risk. Results indicated that the BPD
      group exhibited a greater decrease in suicidal ideation in the months following
      hospitalization than those without a BPD diagnosis. The findings of this study
      indicated that suicidal ideation in adolescents with BPD is not stable, and
      although ideation may decrease quickly after hospitalization, regular assessment
      of ideation is recommended. 

PMID- 24112119
TI  - Amoeba host-Legionella synchronization of amino acid auxotrophy and its role in
      bacterial adaptation and pathogenic evolution.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, invades and
      proliferates within a diverse range of free-living amoeba in the environment, but
      upon transmission to humans, the bacteria hijack alveolar macrophages.
      Intracellular proliferation of L. pneumophila in two evolutionarily distant hosts
      is facilitated by bacterial exploitation of conserved host processes that are
      targeted by bacterial protein effectors injected into the host cell. A key aspect
      of microbe-host interaction is microbial extraction of nutrients from the host,
      but understanding of this is still limited. AnkB functions as a nutritional
      virulence factor and promotes host proteasomal degradation of polyubiquitinated
      proteins generating gratuitous levels of limiting host cellular amino acids.
      Legionella pneumophila is auxotrophic for several amino acids including cysteine,
      which is a metabolically preferred source of carbon and energy during
      intracellular proliferation, but is limiting in both amoebae and humans. We
      propose that synchronization of bacterial amino acids auxotrophy with the host is
      a driving force in pathogenic evolution and nutritional adaptation of L.
      pneumophila and other intracellular bacteria to life within the host cell.
      Understanding microbial strategies of nutrient generation and acquisition in the
      host will provide novel antimicrobial strategies to disrupt pathogen access to
      essential sources of carbon and energy.

PMID- 24112121
TI  - Irritable bowel syndrome-type symptoms in female patients with mild systemic
      lupus erythematosus: frequency, related factors and quality of life.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) impairs quality of life (HRQOL), as
      does systemic lupus erythematosus (SLE). Both are more common in women and are
      associated with fibromyalgia (FM). However, the relationship between IBS and SLE
      and its impact on HRQOL has not been explored. Therefore, we aimed to study the
      frequency and features likely to influence the presence of IBS-type symptoms in
      SLE and their impact on HRQOL. METHODS: Female patients with SLE were studied.
      The presence of IBS-type symptoms and bowel habit subtype were established by
      Rome III criteria and HRQOL was assessed using the SF-36. Fibromyalgia and
      depression were assessed using the American College of Rheumatology criteria and
      CES-D scale, respectively. KEY RESULTS: A total of 105 consecutive patients
      (43.62 +/- 11.34 years old) were included; 48.6% had IBS-type symptoms (SLE+IBS)
      and were classified as IBS-C: 23.5%, IBS-D: 37.3%, and IBS-M: 39.2%. In addition,
      23.8% had FM. SLE+IBS vs Non-IBS SLE patients had higher SLE activity scores
      (2.55 +/- 1.65 vs 1.74 +/- 2.19; p = 0.03), were more likely to have FM (33.0% vs
      14.8%; p = 0.02) and depression (41.1% vs 25.9%, p = 0.04). Logistic multivariate
      analysis showed that IBS-type symptoms were associated with FM (OR = 2.85, 95%
      CI: 1.11-7.43) and depression (OR = 1.07, 95% CI: 1.02-1.13). Finally, SLE+IBS vs
      Non-IBS SLE patients had lower SF-36 scores (49.65 +/- 18.57 vs 62.67 +/- 18.14;
      p = 0.02). CONCLUSIONS & INFERENCES: IBS-type symptoms are highly prevalent among
      women with SLE and are associated with FM and depression. SLE+IBS patients had
      worse HRQOL vs Non-IBS SLE, independently of FM status. We suggest that treating
      IBS symptoms may improve HRQOL in women with SLE.

PMID- 24112122
TI  - Comparative transcriptome analysis between somatic embryos (SEs) and zygotic
      embryos in cotton: evidence for stress response functions in SE development.
AB  - As a product of asexual reproduction in plants, the somatic embryo (SE)
      differentiates into a new plantlet via a zygotic embryogenesis-like process.
      Here, we present the phenotypic and cellular differences between SEs and zygotic
      embryos (ZEs) revealed by histological section scanning using three parallel
      development stages of the two types of embryos of cotton (Gossypium hirsutum cv.
      YZ1), including globular, torpedo and cotyledonary-stages. To identify the
      molecular characteristics of SE development in cotton, the digital gene
      expression system was used to profile the genes active during SE and ZE
      development. A total of 4242 differentially expressed genes (DEGs) were
      identified in at least one developmental stage. Expression pattern and functional
      classification analysis based on these DEGs reveals that SE development exhibits
      a transcriptional activation of stress responses. RT-PCR analysis further
      confirmed enhanced expression levels of stress-related genes in SEs than in ZEs.
      Experimental stress treatment, induced by NaCl and ABA, accelerated SE
      development and increased the transcription of genes related to stress response,
      in parallel with decelerated proliferation of embryogenic calluses under stress
      treatment. Our data reveal that SE development involves the activation of stress
      responses, which we suggest may regulate the balance between cell proliferation
      and differentiation. These results provide new insight into the molecular
      mechanisms of SE development and suggest strategies that can be used for
      regulating the developmental processes of somatic embryogenesis. 

PMID- 24112123
TI  - Impact of chronic kidney disease on the risk of clinical outcomes in patients
      with cancer-associated venous thromboembolism during anticoagulant treatment.
AB  - BACKGROUND: Information on recurrent venous thromboembolic events (VTEs) and
      major bleeding risks during anticoagulant treatment in patients with cancer
      associated VTEs and chronic kidney disease (CKD) is scarce, although it is of
      relevance in establishing better tailored management strategies in these
      patients. OBJECTIVES: We compared risks of recurrent VTEs and major bleeds in
      cancer-associated VTE patients with and without CKD. METHODS: A total of 1684
      patients diagnosed with a cancer-associated VTE between 2001 and 2011 were
      followed for 180 days after VTE diagnosis. Patients were treated mainly with low
      molecular-weight heparin (LMWH) or vitamin-K antagonists (VKA). Primary outcomes
      were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding.
      RESULTS: Recurrent VTEs occurred in 15.9/100 patient years (py) in patients
      without CKD (eGFR > 60 mL min(-1) ), 19.5/100 py in those with CKD stage 3A (eGFR
      45-60 mL min(-1) ), 14.9/100 py in those with CKD 3B (eGFR 30-45 mL min(-1) ),
      and 6.8/100 py in patients with CKD 4-5 (eGFR < 30 mL min(-1) ). Major bleeding
      occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD
      stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD
      4-5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100
      py, respectively. These increased bleeding risks in CKD patients were mainly
      observed in those on LMWH treatment, not VKA. CONCLUSIONS: The risk of major
      bleeding was increased in CKD patients with VTE and cancer, and was most
      prominent in those treated with LMWH and an eGFR < 30 mL min(-1) . These results
      indicate that LMWH should be used with caution in this specific population.

PMID- 24112124
TI  - Differential expression of transglutaminase genes in patients with chronic
      periodontitis.
AB  - OBJECTIVE: Gingival epithelium plays a key role in the protection of oral tissues
      from microbial challenge, especially during the periodontal disease. This study
      was aimed to evaluate levels of mRNA transcripts of different forms of
      transglutaminase in the human gingival tissues from patients with chronic
      periodontitis and relative controls. SUBJECTS AND METHODS: This study included 22
      patients with chronic periodontitis (CP) and 22 healthy controls. For each
      patient, the values of probing depth (PD), clinical attachment level (CAL), and
      bleeding on probing (BOP) were recorded. Gene expression of transglutaminase 1,
      transglutaminase 2, transglutaminase 3, and metalloprotease 2 was evaluated by
      real-time PCR, while that of Factor XIIIA and metalloprotease 9 by RT-PCR.
      RESULTS: The values of all the clinical parameters were significantly higher in
      the CP group than in the healthy control group (P < 0.05). In the CP group, the
      mRNA expression of transglutaminase 1 and transglutaminase 3 was significantly
      decreased in comparison with healthy control group. A slight nonsignificant
      changes of transglutaminase 2 gene expression were observed in samples from CP
      patients in comparison with controls. CONCLUSIONS: These observations suggest
      that transglutaminase gene expression may be modified in response to chronic
      injury in the damaged gingival and emphasizes the key role of these enzymes in
      gingival remodelling/healing and adaptive processes.

PMID- 24112126
TI  - Decision-making and accountability: differences of distribution.
AB  - The cognitive and individual framing of clinical decision-making has been
      undermined in the social sciences by attempts to reframe decision-making as being
      distributed. In various ways, shifts in understanding in social science research
      and theorising have wrested clinical decision-making away from the exclusive
      domain of medical practice and shared it throughout the healthcare disciplines.
      The temporality of decision-making has been stretched from discrete moments of
      cognition to being incrementally built over many instances of time and place, and
      the contributors towards decision-making have been expanded to include non-humans
      such as policies, guidelines and technologies. However, frameworks of
      accountability fail to recognise this distributedness and instead emphasise
      independence of thought and autonomy of action. In this article I illustrate this
      disparity by contrasting my ethnographic accounts of clinical practice with the
      professional codes of practice produced by the General Medical Council and the
      Nursing and Midwifery Council. I argue that a 'thicker' concept of accountability
      is needed; one that can accommodate the diffuseness of decision-making and the
      dependencies incurred in collaborative work. 

PMID- 24112125
TI  - Extended-access, but not limited-access, methamphetamine self-administration
      induces behavioral and nucleus accumbens dopamine response changes in rats.
AB  - To better understand the neurobiology of methamphetamine (METH) dependence and
      the cognitive impairments induced by METH use, we compared the effects of
      extended (12 h) and limited (1 h) access to METH self-administration on locomotor
      activity and object place recognition, and on extracellular dopamine levels in
      the nucleus accumbens and caudate-putamen. Rats were trained to self-administer
      intravenous METH (0.05 mg/kg). One group had progressively extended access up to
      12-h sessions. The other group had limited-access 1-h sessions. Microdialysis
      experiments were conducted during a 12-h and 1-h session, in which the effects of
      a single METH injection (self-administered, 0.05 mg/kg, i.v.) on extracellular
      dopamine levels were assessed in the nucleus accumbens and caudate-putamen
      compared with a drug-naive group. The day after the last 12-h session and the
      following day experimental groups were assessed for their locomotor activities
      and in a place recognition procedure, respectively. The microdialysis results
      revealed tolerance to the METH-induced increases in extracellular dopamine only
      in the nucleus accumbens, but not in the caudate-putamen in the extended-access
      group compared with the control and limited-access groups. These effects may be
      associated with the increased lever-pressing and drug-seeking observed during the
      first hour of drug exposure in the extended-access group. This increase in drug
      seeking leads to higher METH intake and may result in more severe consequences in
      other structures responsible for the behavioral deficits (memory and locomotor
      activity) observed in the extended-access group, but not in the limited-access
      group. 

PMID- 24112127
TI  - A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate
      to-Die Foot-and-Mouth Disease Response Policies I: Benefits of Higher Potency
      Vaccines and Associated NSP DIVA Test Systems in Post-Outbreak Surveillance.
AB  - To rapidly return to trade, countries with OIE status, FMD-free country where
      vaccination is not practised, have destroyed emergency vaccinated animals,
      raising ethical concerns with respect to social values, the environment, animal
      welfare and global food security. This two-part review explores whether science
      could support eligibility to return to previous OIE status in 3 months
      irrespective of vaccinate-to-live or vaccinate-to-die policies. Here, we examine
      the benefits of higher potency (>= 6 PD50 ), high-purity vaccines formulated from
      antigen banks for emergency use, their efficacy and performance in
      differentiating infected from vaccinated animals (DIVA) assays for post-outbreak
      surveillance. From an intensive programme of research, we conclude that high
      quality, higher potency vaccines are proven to reduce FMD virus (FMDV)
      subclinical circulation and the risk of carriers. Broader coverage than predicted
      by serology suggests the potential to hold a few 'key' vaccine strains improving
      logistics and reducing the financial burden of antigen banks. The OIE should
      adopt formal definitions for emergency vaccination and emergency vaccines. In
      terms of supportive tools, we consider that the lack of OIE recognition of DIVA
      tests other than those of PANAFTOSA in cattle is a shortcoming. There is need for
      research on maternal antibody interference with DIVA tests and on the use of such
      tests to establish whether greater purification of vaccines improves performance.
      We consider that alignment of waiting periods for vaccinate-to-live and vaccinate
      to-die in OIE Code Article 8.5.9 1 b. and c. is feasible until an acceptable
      level of statistical certainty for surveillance or target probability of freedom
      is established to substantiate the absence of FMDV infection or circulation. It
      is surveillance intensity rather than waiting periods that establishes the risk
      of residual FMDV. EU Directive 2003/85/EC implicitly recognizes this, permitting
      derogation of the OIE waiting periods.

PMID- 24112128
TI  - Including citizens in institutional reviews: expectations and experiences from
      the Dutch Healthcare Inspectorate.
AB  - BACKGROUND: Recent changes in the structure and policy context of Dutch health
      care have placed the issue of citizen participation high on the agenda of the
      Dutch Healthcare Inspectorate (IGZ), which conducts quality and safety reviews in
      medical practices and health-care institutions. With a few exceptions, the
      potential role that citizens can play in the regulation of health-care
      institutions is overlooked in research on patient/citizen participation in health
      care. OBJECTIVE: This research addressed the following question: What are the
      (political) expectations for increasing citizen participation in health-care
      regulation and how do these compare to regulators' expectations and experiences
      in practice? DESIGN: Because of the largely explorative nature of this study, we
      used qualitative methods (document and web analysis, focus groups and interviews)
      to answer this question. RESULTS: Our study shows that inspectors already have
      experience with participatory formats that lead to important information. There
      are three areas where the IGZ is currently increasing citizen participation: (i)
      providing individuals with information about inspectorate processes and
      activities, (ii) including patients as sources of information, and (iii) formally
      reviewing how citizen participation is ensured by health-care institutions. In
      situations where the patient has the clearest overview of the whole care
      trajectory, intensive methods of participation deliver valuable information.
      CONCLUSIONS: It is important to target participation activities and to capitalize
      on existing opportunities and activities, rather than creating participation
      activities for the sake of participation. In this regard, further research on the
      effectiveness and efficacy of different participatory strategies is necessary.

PMID- 24112130
TI  - Long pentraxin PTX3 attenuates ischemia reperfusion injury in a cardiac
      transplantation model.
AB  - Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation, and
      inflammatory processes play a major role in myocardial IR injury. Long pentraxin
      3 (PTX3) is a member of a phylogenetically conserved group of acute-phase
      reactants that are involved in inflammation and innate immunity. In our study,
      hearts of C57Bl/6 mice were flushed and stored in cold Bretschneider solution for
      8 h and then transplanted into syngeneic recipient. We found that both mRNA and
      protein levels of PTX3 were increased following myocardial IR injury;
      neutralizing antibody against PTX3 aggravated cardiomyocyte apoptosis and
      recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h
      after myocardial IR injury was reduced by exogenous PTX3 administration and
      increased by PTX3 neutralization in comparison with control. Cardiac output at 60
      mmHg of afterload pressure was also increased in hearts with exogenous PTX3
      administration and decreased with PTX3 neutralization (PTX3: 58.4 +/- 7.4 ml/min;
      CONTROL: 24.5 +/- 3.8 ml/min; Anti-PTX3: 11.6 +/- 1.7 ml/min; P < 0.05).
      Furthermore, PTX3 restricted expansion of gammadelta T cell that was the major
      source of IL-17A and down-regulated expression of IL-23 and IL-17A. In
      conclusion, PTX3 played a protective role in cardiomyocyte IR injury. PTX3
      ameliorated cardiomyocyte apoptosis and infiltration of neutrophil and macrophage
      and then improved hemodynamic performance. This was associated with restricted
      gammadelta T-cell expansion and decreased IL-23/IL-17A expression.

PMID- 24112129
TI  - The potential impact of routine testing of individuals with HIV indicator
      diseases in order to prevent late HIV diagnosis.
AB  - BACKGROUND: The aim of our work was to evaluate the potential impact of the
      European policy of testing for HIV all individuals presenting with an indicator
      disease, to prevent late diagnosis of HIV. We report on a retrospective analysis
      among individuals diagnosed with HIV to assess whether a history of certain
      diseases prior to HIV diagnosis was associated with the chance of presenting late
      for care, and to estimate the proportion of individuals presenting late who could
      have been diagnosed earlier if tested when the indicator disease was diagnosed.
      METHODS: We studied a large cohort of individuals newly diagnosed with HIV
      infection in 13 counselling and testing sites in the Lazio Region, Italy
      (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis
      infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and
      tuberculosis. Logistic regression analysis was performed to estimate association
      of occurrence of at least one indicator disease with late HIV diagnosis. RESULTS:
      In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735).
      Individuals reporting at least one indicator disease before HIV diagnosis (29% of
      the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5
      0.8) compared to those who did not report a previous indicator disease. 52/890
      (5.8%) late presenters were probably already infected at the time the indicator
      disease was diagnosed, a median of 22.6 months before HIV diagnosis. CONCLUSIONS:
      Our data suggest that testing for HIV following diagnosis of an indicator disease
      significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5%
      of late HIV presenters, diagnosis could have been anticipated if they had been
      tested when an HIV indicator disease was diagnosed.However, this strategy for
      enhancing early HIV diagnosis needs to be complemented by client-centred
      interventions that aim to increase awareness in people who do not perceive
      themselves as being at risk for HIV.

PMID- 24112131
TI  - Failure to process dentin sialophosphoprotein into fragments leads to periodontal
      defects in mice.
AB  - Dentin sialophosphoprotein (DSPP) plays a vital role in dentinogenesis.
      Previously, we showed that, in addition to dentin, DSPP is also highly expressed
      in alveolar bone and cellular cementum, and plays a crucial role in maintaining
      periodontal integrity; Dspp-deficient mice demonstrate severe periodontal
      defects, including alveolar bone loss, decreased cementum deposition, abnormal
      osteocyte morphology in the alveolar bone, and apical migration of periodontal
      ligament. Dentin sialophosphoprotein in dentin and bone is cleaved into NH2 
      terminal and COOH-terminal fragments. Whilst our previous study showed that the
      proteolytic processing of DSPP is critical for dentinogenesis, it is unclear
      whether the post-translational cleavage of DSPP also plays an essential role in
      maintaining a healthy periodontium. In this study, we analyzed the periodontal
      tissues from transgenic mice expressing the uncleavable full-length DSPP in the
      Dspp knockout (Dspp-KO) background (named 'Dspp-KO/D452A-Tg mice'), in comparison
      with those from wild-type mice, Dspp-KO mice, and mice expressing the normal Dspp
      transgene in the Dspp-KO background (designated 'Dspp-KO/normal-Tg mice'). We
      found that transgenic expression of the normal DSPP fully rescued the periodontal
      defects of the Dspp-KO mice, whereas this was not the case in Dspp-KO/D452A-Tg
      mice. These results indicate that proteolytic processing of DSPP is essential to
      periodontal integrity.

PMID- 24112132
TI  - Influenza A virus survival in water is influenced by the origin species of the
      host cell.
AB  - BACKGROUND: Influenza A viruses have an envelope made of a lipid bilayer and two
      surface glycoproteins, the hemagglutinin and the neuraminidase. The structure of
      the virus is directly dependent on the genetic makeup of the viral genome except
      the glycosylation moieties and the composition of the lipid bilayer. They both
      depend on the host cell and are in direct contact with the environment, such as
      air or water. Virus survival is important for virus transmission from
      contaminated waters in the case of wild aquatic birds or from contaminated
      surface or air for humans. OBJECTIVE: The objective of this study was to check
      whether the origin species of the host cell has an influence on influenza A virus
      survival. METHOD: The persistence in water at 35 degrees C of viruses grown on
      either mammalian cells or avian cells and belonging to two different subtypes
      H1N1 and H5N1 was compared. RESULTS: Both H5N1 and H1N1 viruses remained
      infectious for periods of time as long as 19-25 days, respectively. However,
      within the same subtype, viruses grown on mammalian cells were more stable in
      water at 35 degrees C than their counterparts grown on avian cells, even for
      viruses sharing the same genetic background. CONCLUSIONS: This difference in
      virus stability outside the host is probably connected to the nature of the lipid
      bilayer taken from the cell or to the carbohydrate side chains of the virus
      surface glycoproteins. Moreover, the long-lasting survival time might have a
      critical role in the ecology of influenza viruses, especially for avian viruses.

PMID- 24112133
TI  - Chromosome 9p21 primary open-angle glaucoma susceptibility locus: a review.
AB  - Primary open-angle glaucoma (POAG) is a genetically complex disease. Genome-wide
      association study (GWAS) is a particularly useful tool in the search for genetic
      contributions to glaucoma. Recently, chromosome 9p21 has become a major focus of
      research endeavour, with multiple genome-wide association studies suggesting
      associations to POAG. Herein, we provide a review of the chromosome 9p21
      susceptibility locus as a risk factor for POAG. 

PMID- 24112134
TI  - Evaluation of drinking patterns and their impact on alcohol-related aggression: a
      national survey of adolescent behaviours.
AB  - BACKGROUND: Although there have been a wide range of epidemiological studies
      examining the impact of patterns of alcohol consumption among adolescents, there
      remains considerable variability in both defining these patterns and the ability
      to comprehensively evaluate their relationship to behavioural patterns. This
      study explores a new procedure for defining and evaluating drinking patterns and
      integrating well-established indicators. The composite measure is then used to
      estimate the impact of these patterns on alcohol-related aggressive behaviour
      among Italian adolescents. METHODS: Data were collected as part of the 2011
      European School Survey Project on Alcohol and other Drugs (ESPAD). A national
      sample of 14,199 students aged 15-19 years was collected using an anonymous, self
      administered questionnaire completed in a classroom setting. Drinking patterns
      were established using principal component analysis. Alcohol-related aggression
      was analysed as to its relationship to patterns of drinking, behaviour of friends
      towards alcohol use, substance use/abuse, school performance, family
      relationships and leisure activities. RESULTS: Several specific drinking patterns
      were identified: "Drinking to Excess" (DE), "Drinking with Intoxication" (DI) and
      "Drinking but Not to Excess" (DNE). A higher percentage of males were involved in
      alcohol-related aggression compared with females. In males, the DE and DI
      patterns significantly increased the likelihood of alcohol-related aggression,
      whereas the DNE pattern was negatively associated. Similar results were found in
      females, although the DI pattern was not significantly associated with alcohol
      related aggression. Overall, cigarette smoking, illegal drug use, truancy,
      limited parental monitoring, frequent evenings spent outside of the home and peer
      influence associated strongly with alcohol-related aggression. CONCLUSIONS: Our
      findings suggest that drinking patterns, as uniquely monitored with an integrated
      metric, can: 1) explain drinking habits better than commonly used indicators of
      alcohol use and 2) provide a better understanding of behavioural risks such as
      alcohol-related aggression. Environmental background also appears to strongly
      associate with this type of aggressive behaviour.

PMID- 24112135
TI  - A psychometric comparison of three scales and a single-item measure to assess
      sexual satisfaction.
AB  - This study was designed to systematically compare and contrast the psychometric
      properties of three scales developed to measure sexual satisfaction and a single
      item measure of sexual satisfaction. The Index of Sexual Satisfaction (ISS),
      Global Measure of Sexual Satisfaction (GMSEX), and the New Sexual Satisfaction
      Scale-Short (NSSS-S) were compared to one another and to a single-item measure of
      sexual satisfaction. Conceptualization of the constructs, distribution of scores,
      internal consistency, convergent validity, test-retest reliability, and factor
      structure were compared between the measures. A total of 211 men and 214 women
      completed the scales and a measure of relationship satisfaction, with 33% (n =
      139) of the sample reassessed two months later. All scales demonstrated
      appropriate distribution of scores and adequate internal consistency. The GMSEX,
      NSSS-S, and the single-item measure demonstrated convergent validity. Test-retest
      reliability was demonstrated by the ISS, GMSEX, and NSSS-S, but not the single
      item measure. Taken together, the GMSEX received the strongest psychometric
      support in this sample for a unidimensional measure of sexual satisfaction and
      the NSSS-S received the strongest psychometric support in this sample for a
      bidimensional measure of sexual satisfaction. 

PMID- 24112136
TI  - From health care volume to health care value--success strategies for rural health
      care providers.

PMID- 24112137
TI  - Autism and normative sexual development: a narrative review.
AB  - AIMS AND OBJECTIVES: To explore the existing knowledge on sexuality and autism
      spectrum disorders. To this end, the concept of normative sexual development was
      used as an organising framework. BACKGROUND: Sexual health can be seen as a
      developmental task for all children, adolescents and adults. Core autism features
      are related with skills central to sexual development and functioning. More
      insight in sexual development in people with autism is relevant for education,
      support and interventions by parents and professionals in somatic and mental
      health care. METHODS: A comprehensive search of scientific online databases and
      reference lists was conducted. Publications based on qualitative and quantitative
      research, including case studies, were selected. RESULTS: Fifty-five articles and
      reports were selected and discussed. Information was grouped according to three
      domains: sexual behaviour, sexual selfhood and sexual socialisation. CONCLUSION:
      Sexual development is a part of life for people with autism of all developmental
      levels and is generally understudied in this population. Most information was
      available on behavioural aspects and experiences of socialising agents, such as
      parents and professionals. Developmental processes and the relation between
      sexual behaviour, selfhood and socialisation remained unclear. RELEVANCE TO
      CLINICAL PRACTICE: Nurses working in schools, institutions and general health
      care support children, adolescents and adults with autism and advice their
      families, teachers, other educators and caregivers on sexuality issues. They can
      have an important role in daily assessment and support of this developmental
      domain by actively enquiring about the different aspects of sexual development
      and by offering information. Our findings offer an overview on the existing
      knowledge and support the idea that sexual development is normative for people
      with autism just as for anybody else.

PMID- 24112138
TI  - Analysis of the factors affecting the formation of the microbiome associated with
      chronic osteomyelitis of the jaw.
AB  - Chronic osteomyelitis of the jaw (COMJ) is one of the most intractable diseases
      among head and neck infections. Antimicrobial agents are routinely administered
      for COMJ without sufficient bacterial information, resulting in frequent
      treatment failures. To improve our knowledge of the bacterial aetiology of COMJ
      and to assist in the development of effective treatments, we performed a
      comprehensive analysis of the microbiome. Sixteen patients with four clinical
      types of COMJ (four with suppurative osteomyelitis, three with osteoradionecrosis
      of the jaw, four with primary chronic osteomyelitis, and five with bisphosphonate
      related osteonecrosis of the jaw) were enrolled in this study. Bone samples were
      subjected to bacterial community comparisons by 16S rRNA gene pyrosequencing. As
      a result, we clarified that COMJ was caused by a far greater range of bacterial
      species (12 phyla and 163 genera) than previously reported. Moreover, the
      bacterial structures in COMJ changed dramatically with disease stage and the
      condition of the affected bone. Multiple correlation analyses revealed that
      sequestration and bone exposure could affect the community structure. On the
      basis of these factors, we reclassified COMJ into three clinical stages: I,
      inflamed or sclerotic bone without exposure; II, sequestrum without exposure; and
      III, exposed sequestrum. In stage II, the bacterial diversity was significantly
      lower, and the anaerobe genera Fusobacterium, Tannerella (formerly Bacteroides)
      and Porphyromonas were more abundant, than observed during other stages. Because
      these bacteria habitually reside in any clinical stage, they were considered to
      constitute the core microbiome of COMJ. Targeting these bacteria should lead to
      the development of effective preventive measures and cures.

PMID- 24112139
TI  - Quantification of HBG mRNA in primary erythroid cultures: prediction of the
      response to hydroxyurea in sickle cell and beta-thalassemia.
AB  - BACKGROUND AND OBJECTIVE: Increased expression of fetal hemoglobin (HbF) may
      ameliorate the clinical course of hemoglobinopathies like sickle cell disease
      (SCD) and beta-thalassemia. Hydroxyurea (HU) can stimulate HbF production in
      these diseases but the response is highly variable indicating the utility of
      developing an in vitro test to predict the patient's response to HU. We assessed
      whether the HbF response of patients with SCD and thalassemia intermedia (TI) to
      HU correlates with HBG (both gamma-globin genes) expression in their cultured
      erythroid progenitors following exposure to HU. PATIENTS AND METHODS: We exposed
      primary erythroid cultures from peripheral blood mononuclear cells from 30
      patients with SCD and 15 with TI to HU and measured HBG mRNA by real-time
      quantitative PCR. The same patients were then treated with HU and their HbF
      response after treatment with a stable dose of HU was compared with the mRNA
      results in cultured cells. RESULTS AND CONCLUSION: The fold increase in HBG mRNA
      in erythroid progenitors was similar to the fold increase in HbF in vivo.
      Quantification of HBG mRNA in erythroid progenitor cell cultures from patients
      with SCD and TI is predictive of their clinical response to HU.

PMID- 24112140
TI  - First report of granulomatous mastitis associated with Sjogren's syndrome.
AB  - Granulomatous mastitis is a rare and often considered as idiopathic disease.
      However, clinical examination and thorough diagnostic investigations have to be
      carried out in order to identify cases that are secondary to infections or
      systemic diseases since these forms may be cured with appropriate etiologic
      treatment. To the best of our knowledge, this report is the first to describe the
      association of granulomatous mastitis with Sjogren's syndrome. We discuss the
      clinical, pathological and therapeutic implications of this association. 

PMID- 24112141
TI  - The novel HLA-C*12:92 allele is characterized by one amino acid exchange located
      in the T-cell receptor binding region of the alpha 2 domain.
AB  - HLA-C*12:92 contains one amino acid exchange in the T-cell receptor binding
      region. 

PMID- 24112142
TI  - Impact of professional nursing practice environment and psychological empowerment
      on nurses' work engagement: test of structural equation modelling.
AB  - AIM: This study aimed to investigate the influence of professional nursing
      practice environment and psychological empowerment on nurses' work engagement.
      BACKGROUND: Previous researchers have acknowledged the positive influence that
      nurse work environment and psychological empowerment have on engagement. However,
      less is known about the mechanisms that explain the links between them. METHOD: A
      predictive, non-experimental design was used to test the model in a random sample
      of 300 clinical nurses from two tertiary first class hospitals of Tianjin, China.
      The Utrecht Work Engagement Scale, the Practice Environment Scale of the Nursing
      Work Index and the Psychological Empowerment Scale were used to measure the study
      variables. RESULT: Structural equation modelling revealed a good fit of the model
      to the data based on various fit indices (P = 0.371, chi(2) /df = 1.056, goodness
      of fit index = 0.967), which indicated that both professional practice
      environment and psychological empowerment could positively influence work
      engagement directly, and professional practice environment could also indirectly
      influence work engagement through the mediation of psychological empowerment.
      CONCLUSION: The study hypotheses were supported. Psychological empowerment was
      found to mediate the relationship between practice environments and work
      engagement. IMPLICATIONS FOR NURSING MANAGEMENT: Administrators should provide a
      professional nursing practice environment and empower nurses psychologically to
      increase nurse engagement.

PMID- 24112144
TI  - Synthesis, spectroscopic characterization, and determination of the solution
      association energy of the dimer [Co{N(SiMe3)2}2]2: magnetic studies of low
      coordinate Co(II) silylamides [Co{N(SiMe3)2}2L] (L = PMe3, pyridine, and THF) and
      related species that reveal evidence of very large zero-field splittings.
AB  - The synthesis, magnetic, and spectroscopic characteristics of the synthetically
      useful dimeric cobalt(II) silylamide complex [Co{N(SiMe3)2}2]2 (1) and several of
      its Lewis base complexes have been investigated. Variable-temperature nuclear
      magnetic resonance (NMR) spectroscopy of 1 showed that it exists in a monomer
      dimer equilibrium in benzene solution and has an association energy (DeltaGreacn)
      of -0.30(20) kcal mol(-1) at 300 K. Magnetic data for the polycrystalline, red
      brown [Co{N(SiMe3)2}2]2 (1) showed that it displays strong antiferromagnetic
      exchange coupling, expressed as -2JexS1S2, between the two S = (3)/2 cobalt(II)
      centers with a Jex value of -215(5) cm(-1), which is consistent with its bridged
      dimeric structure in the solid state. The electronic spectrum of 1 in solution is
      reported for the first time, and it is shown that earlier reports of the melting
      point, synthesis, electronic spectrum, and magnetic studies of the monomer
      "Co{N(SiMe3)2}2" are consistent with those of the bright green-colored
      tetrahydrofuran (THF) complex [Co{N(SiMe3)2}2(THF)] (4). Treatment of 1 with
      various Lewis bases yielded monomeric three-coordinated species
      [Co{N(SiMe3)2}2(PMe3)] (2), and [Co{N(SiMe3)2}2(THF)] (4), as well as the
      previously reported [Co{N(SiMe3)2}2(py)] (3)-and the four-coordinated species
      [Co{N(SiMe3)2}2(py)2] (5) in good yields. The paramagnetic complexes 2-4 were
      characterized by electronic and (1)H NMR spectroscopy, and by X-ray
      crystallography in the case of 2 and 4. Magnetic studies of 2-5 and of the known
      three-coordinated cobalt(II) species [Na(12-crown-4)2][Co{N(SiMe3)2}3] (6) showed
      that they have considerably larger chiMT products and, hence, magnetic moments,
      than the spin-only values of 1.875 emu K mol(-1) and 3.87 MUB, which is
      indicative of a significant zero-field splitting and g-tensor anisotropy
      resulting from the pseudo-trigonal crystal field. A fit of chiMT for 2-6 yields a
      large g-tensor anisotropy, large negative D-values (between -62 cm(-1) and -82
      cm(-1)), and E-values between +/-10 cm(-1) and +/-21 cm(-1). 

PMID- 24112145
TI  - Psychological traits influence autonomic nervous system recovery following
      esophageal intubation in health and functional chest pain.
AB  - BACKGROUND: Esophageal intubation is a widely utilized technique for a diverse
      array of physiological studies, activating a complex physiological response
      mediated, in part, by the autonomic nervous system (ANS). In order to determine
      the optimal time period after intubation when physiological observations should
      be recorded, it is important to know the duration of, and factors that influence,
      this ANS response, in both health and disease. METHODS: Fifty healthy subjects
      (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome
      III defined functional chest pain (nine male, median age of 38.7 years, range 28
      59 years) had personality traits and anxiety measured. Subjects had heart rate
      (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and
      parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at
      baseline and in response to per nasum intubation with an esophageal catheter.
      CSI/CVT recovery was measured following esophageal intubation. KEY RESULTS: In
      all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin
      conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac
      sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear
      regression analysis demonstrated that longer CVT recovery times were
      independently associated with higher neuroticism (p < 0.001). Patients had
      prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s
      vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively).
      CONCLUSIONS & INFERENCES: Esophageal intubation activates a flight/flight ANS
      response. Future studies should allow for at least 10 min of recovery time.
      Consideration should be given to psychological traits and disease status as these
      can influence recovery.

PMID- 24112146
TI  - Programming effects of high-carbohydrate feeding of larvae on adult glucose
      metabolism in zebrafish, Danio rerio.
AB  - The aim of the present study was to determine the potential long-term metabolic
      effects of early nutritional programming on carbohydrate utilisation in adult
      zebrafish (Danio rerio). High-carbohydrate diets were fed to fish during four
      ontogenetic stages: from the first-feeding stage to the end of the yolk-sac
      larval stage; from the first-feeding stage to 2 d after yolk-sac exhaustion;
      after yolk-sac exhaustion for 3 or 5 d. The carbohydrate stimuli significantly
      increased the body weight of the first-feeding groups in the short term. The
      expression of genes was differentially regulated by the early dietary
      intervention. The high-carbohydrate diets resulted in decreased plasma glucose
      levels in the adult fish. The mRNA levels and enzyme activities of glucokinase,
      pyruvate kinase, alpha-amylase and sodium-dependent glucose co-transporter 1 were
      up-regulated in the first-feeding groups. There was no significant change in the
      mRNA levels of glucose-6-phosphatase (G6Pase) in any experimental group, and the
      activity of G6Pase enzyme in the FF-5 (first feeding to 2 d after yolk-sac
      exhaustion) group was significantly different from that of the other groups. The
      expression of phosphoenolpyruvate carboxykinase gene in all the groups was
      significantly decreased. In the examined early programming range, growth
      performance was not affected. Taken together, data reported herein indicate that
      the period ranging from the polyculture to the external feeding stage is an
      important window for potential modification of the long-term physiological
      functions. In conclusion, the present study demonstrates that it is possible to
      permanently modify carbohydrate digestion, transport and metabolism of adult
      zebrafish through early nutritional programming.

PMID- 24112147
TI  - Valencene synthase from the heartwood of Nootka cypress (Callitropsis
      nootkatensis) for biotechnological production of valencene.
AB  - Nootkatone is one of the major terpenes in the heartwood of the Nootka cypress
      Callitropsis nootkatensis. It is an oxidized sesquiterpene, which has been
      postulated to be derived from valencene. Both valencene and nootkatone are used
      for flavouring citrus beverages and are considered among the most valuable
      terpenes used at commercial scale. Functional evaluation of putative terpene
      synthase genes sourced by large-scale EST sequencing from Nootka cypress wood
      revealed a valencene synthase gene (CnVS). CnVS expression in different tissues
      from the tree correlates well with nootkatone content, suggesting that CnVS
      represents the first dedicated gene in the nootkatone biosynthetic pathway in C.
      nootkatensis The gene belongs to the gymnosperm-specific TPS-d subfamily of
      terpenes synthases and its protein sequence has low similarity to known citrus
      valencene synthases. In vitro, CnVS displays high robustness under different pH
      and temperature regimes, potentially beneficial properties for application in
      different host and physiological conditions. Biotechnological production of
      sesquiterpenes has been shown to be feasible, but productivity of microbial
      strains expressing valencene synthase from Citrus is low, indicating that
      optimization of valencene synthase activity is needed. Indeed, expression of CnVS
      in Saccharomyces cerevisiae indicated potential for higher yields. In an
      optimized Rhodobacter sphaeroides strain, expression of CnVS increased valencene
      yields 14-fold to 352 mg/L, bringing production to levels with industrial
      potential.

PMID- 24112148
TI  - Can cancer registries show whether treatment is contributing to survival
      increases for melanoma of the skin at a population level?
AB  - RATIONALE, AIMS AND OBJECTIVES: It is uncertain whether survival increases from
      melanoma recorded by some population registries include a treatment effect. The
      US Surveillance, Epidemiology and End Results (SEER) programme has good data
      quality control, large numbers of cases enabling high statistical precision and
      summary stage plus thickness, which we consider to be a best-case population
      registry scenario to investigate potential for a treatment effect. We have
      investigated SEER data to indicate whether survivals increases are fully
      attributable to earlier diagnosis and other non-treatment factors. METHODS:
      Through relative survival regression, the effects of diagnostic period on 5-year
      excess mortality were investigated, adjusting for socio-demographic factors,
      lesion sub-site, histology, thickness and stage at diagnosis in 1990-2009 (n = 99
      690 cases). RESULTS: The reduction in excess mortality (95% confidence interval)
      between 1990-1999 and 2000-2009 was 31 (20-41)% for localised melanoma, 18 (12
      22)% for regional melanoma and 3 (-5-10)% for melanomas with distant spread.
      Younger age was predictive of a greater percentage reduction. Treatment benefits
      are inferred from the higher survivals in 2000-2009 but uncertainty remains due
      to incomplete data to adjust for non-treatment factors and a lack of treatment
      data. CONCLUSIONS: Registries should use new information systems to collect more
      complete data on stage, other prognostic indicators, co-morbidities and
      treatment, to provide more definitive and detailed information on population
      effects of cancer control.

PMID- 24112149
TI  - Evaluation of the efficacy and safety of tiotropium bromide (5 ug) inhaled via
      Respimat in Chinese patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: A pharmacokinetic study in an Asian population showed that tiotropium
      5 ug via Respimat leads to the same plasma levels compared to 18 ug via
      HandiHaler. The objective of the trial was to compare the efficacy and safety of
      longterm treatment (1 year) with tiotropium bromide (5 ug) via Respimat(r) with
      placebo in patients with chronic obstructive pulmonary disease (COPD). METHODS: A
      total of 3991 patients were randomized in this double-blind, placebo controlled,
      parallel group study, while in China 338 patients (309 males, 29 females)
      received either tiotropium bromide (n = 167) or placebo (n = 171). Tiotropium
      bromide solution or matching placebo was delivered via Respimat(r) at a dosage of
      5 ug (2*2.5 ug/puff) once daily for 48 weeks. Co-primary endpoints were trough
      forced expiratory volume in one second (FEV1) and the time to first exacerbation.
      RESULTS: Statistically significant improvements in trough FEV1 and trough forced
      vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48
      compared with those in the placebo group. A statistically significant difference
      (P = 0.0027) in favour of tiotropium was also observed for the time to first
      exacerbation. The total numbers of exacerbations during treatment were 90 and 128
      in the tiotropium and placebo groups, respectively, with a rate ratio of 0.69 (P
      = 0.0164). The difference between the treatment groups in the adjusted mean
      changes from baseline of St. George Respiratory Questionnaire (SGRQ) total score
      was -3.9 (95% CI: -7.5, -0.2) and was of statistical significance (P = 0.0367).
      The incidences of serious adverse events (SAEs) in the tiotropium and placebo
      groups were 16.2% and 17.0%, respectively. Seven deaths occurred whilst patients
      were on treatment, four in the tiotropium group and three in the placebo group,
      all of which were assessed as non-related study drugs by the investigators.
      CONCLUSIONS: Tiotropium significantly improved lung function and quality of life,
      delayed the time to first exacerbation, reduced the number of exacerbations.
      Overall, tiotropium was well tolerated.

PMID- 24112150
TI  - CD8(+) Tc-lymphocytes immunodeviation in peripheral blood and airway from
      patients of chronic obstructive pulmonary disease and changes after short-term
      smoking cessation.
AB  - BACKGROUND: Cigarette smoke induces an acute but persisting inflammation in
      peripheral blood and airway in chronic obstructive pulmonary disease (COPD), and
      CD8(+) Tc-lymphocytes are considered as a key role in this process. We aimed to
      investigate the Tc-lymphocytes immunodeviation in system and local airway of COPD
      patients and changes of the immunodeviation after short-term smoking cessation.
      METHODS: Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were
      collected from 42 patients (14 COPD patients, 16 smokers with normal lung
      function and 12 nonsmokers), while PB and induced sputum (IS) were obtained from
      other 19 patients (10 quitting smokers and 9 continuing smokers) at baseline and
      follow-up respectively of 4-week smoking cessation. Percentages of CD8(+) Tc
      lymphocytes (%CD3(+)) and Tc1/Tc2 ratios were measured by flow cytometry.
      RESULTS: Percentages of CD8(+) Tc-lymphocytes were higher in COPD patients than
      those in smokers and nonsmokers in both PB and BALF. Tc1/Tc2 ratio in PB and in
      BALF from COPD patients was greater than that from smokers and nonsmokers and
      negatively correlated with FEV1 %pre. When comparing the ratios between PB and
      BALF, significantly positive correlation was found in COPD patients. Furthermore,
      after 4-week smoking cessation, percentages of CD8(+) Tc-lymphocytes in PB and IS
      in quitting smokers were decreased compared to that in baseline and continuing
      smokers, whereas Tc1/Tc2 ratios were not influenced. CONCLUSIONS: CD8(+) Tc1
      trend immunodeviation profiles occurred in both system and local airway of COPD
      patients. This exceptional immunodeviation could not be relieved by short-term
      smoking cessation.

PMID- 24112151
TI  - A new method for rating dyspnea during exercise in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The Borg scale is most commonly used to measure dyspnea in China.
      However, many patients that find it is difficult to distinguish the labeled
      numbers corresponding to different dyspnea scores. We developed a new method to
      rate dyspnea, which we call the count scale (CS). It includes the count scale
      number (CSN) and count scale time (CST). The aims of the present study were to
      determine the reproducibility and sensitivity of the CS during exercise in
      patients with chronic obstructive pulmonary disease (COPD). METHODS: Fourteen
      male patients with COPD (aged 58.00 +/- 7.72 years) participated in this study. A
      progressive incremental exercise and a 6-minute constant work exercise test were
      performed every 2 to 3 days for a total of 3 times. The CS results were evaluated
      at rest and at 30% and 70% of maximal workload (Wmax) and Wmax. The Borg scales
      were obtained during exercise. RESULTS: No significant differences occurred
      across the three trials during exercise for the CS and Borg scores. The CSN and
      CST were more varied at Wmax (coefficient of variation (CV) = (22.28 +/- 16.96)%
      for CSN, CV = (23.08 +/- 19.11)% for CST) compared to 30% of Wmax (CV = (11.92 +/
      8.78)% for CSN, CV = (11.16 +/- 9.96)% for CST) and 70% of Wmax (CV = (9.08 +/-
      7.09)% for CSN, CV = (12.19 +/- 12.32)% for CST). Dyspnea ratings with either CSN
      or CST tended to decrease at the higher workload compared to the lower workload.
      CSN and CST scores were highly correlated (r = 0.861, P < 0.001). CSN was
      negatively correlated with Borg scores (r = -0.363, P = 0.001). Similar results
      were obtained for the relationship between CST and Borg scores (r = -0.345, P =
      0.003). CONCLUSION: We concluded that the CS is simple and reproducible when
      measuring dyspnea during exercise in patients with COPD.

PMID- 24112152
TI  - Endobronchial mucormycosis showing as a bronchial tumor.

PMID- 24112153
TI  - High serum interleukin-6 level is associated with increased risk of delirium in
      elderly patients after noncardiac surgery: a prospective cohort study.
AB  - BACKGROUND: The relationship between inflammation and delirium remains to be
      determined. The purposes of this study were to investigate the association
      between serum interleukin-6 levels and the occurrence of delirium in elderly
      patients after major noncardiac surgery. METHODS: A total of 338 elderly patients
      (60 years of age and over) undergoing major noncardiac surgery were enrolled.
      Blood samples were obtained before anesthesia and in the first postoperative
      morning and serum interleukin-6 concentrations were measured. Delirium was
      assessed twice daily by the confusion assessment method for the Intensive Care
      Unit during the first three postoperative days. Survival analyses were performed
      to assess the relationship between the serum IL-6 level and the occurrence of
      postoperative delirium. RESULTS: Postoperative delirium occurred in 14.8% (50 of
      338) of patients. High serum interleukin-6 levelsafter surgery were significantly
      associated with increased risk of the occurrence of postoperative delirium
      (hazard ratio 1.514, 95% confidence interval 1.155-1.985, P = 0.003). Other
      independent predictors of delirium included increasing age, poor preoperative New
      York Heart Association classification, low preoperative Mini-Mental State
      Examination score, and high total postoperative Visual Analogue Scale pain score.
      Patients who developed delirium had a prolonged hospital stay after surgery.
      CONCLUSIONS: Delirium is a frequent complication in elderly patients after
      noncardiac surgery. High serum interleukin-6 level after surgery is associated
      with increased risk of the occurrence of postoperative delirium.

PMID- 24112154
TI  - Predicting value of serum soluble ST2 and interleukin-33 for risk stratification
      and prognosis in patients with acute myocardial infarction.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is a common cardiac emergency with
      high mortality. Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac
      diseases. The present study is to investigate the predictive value of sST2 and
      interleukin-33 (IL-33) for risk stratification and prognosis in patients with
      AMI. METHODS: Fifty-nine patients with AMI, whose chief complaint was chest pain
      or dyspnea, were selected for our study. Physical examination, chest radiograph,
      electrocardiograph (ECG), biomarkers of myocardial infarction, NT-proBNP,
      echocardiography and other relevant examinations were performed to confirm the
      diagnosis of AMI. Thirty-six healthy people were chosen as the control group.
      Serum samples from these subjects (patients within 24 hours after acute attack)
      were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked
      immuno-sorbent assay (ELISA) kit. The follow-up was performed on the 7th day,
      28th day, 3rd month and 6th month after acute attack. According to the follow-up
      results we defined the end of observation as recurrence of AMI or any causes of
      death. RESULTS: Median sST2 level of the control group was 9.38 ng/ml and that of
      AMI patients was 29.06 ng/ml. Compared with the control group, sST2 expression in
      the AMI group was significantly different (P < 0.001). In contrast, the IL-33
      level showed no significant difference between the two groups. Serum sST2 was a
      predictive factor independent of other variables and may provide complementary
      information to NT-proBNP or GRACE risk score. IL-33 had no relationship to
      recurrence of AMI. Both sST2 and the IL-33/sST2 ratio were correlated with the 6
      month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.
      CONCLUSIONS: Early in the course (<24 hours) of AMI, sST2 usually increases
      markedly. The increase of sST2 has an independent predictive value for the
      prognosis in AMI patients and provides complementary information to NT-proBNP or
      GRACE risk score. The IL-33/sST2 ratio correlates with the 6-month prognosis of
      AMI patients. However, there is no significant relationship between IL-33 and the
      prognosis of AMI patients.

PMID- 24112155
TI  - Clinical and pathological features and surgical treatment of Budd-Chiari syndrome
      associated hepatocellular carcinoma.
AB  - BACKGROUND: Budd-Chiari syndrome (BCS) is characterized by liver sinusoidal
      congestion, ischemic liver cell damage, and liver portal hypertension caused by
      hepatic venous outflow constriction. The aim of this research was to investigate
      the clinicopathological features of BCS-associated hepatocellular carcinoma (HCC)
      and explore its surgical treatment and prognosis. METHODS: Clinical data from 38
      patients with BCS-associated HCC who were surgically treated in our hospital from
      July 1998 to August 2010 were retrospectively analyzed. The clinicopathological
      features and prognosis of patients with BCSassociated HCC and surgical treatment
      for BCS-associated HCC were investigated. RESULTS: Compared to the patients with
      hepatitis B virus (HBV)-associated HCC, the patients with BCS-associated HCC
      showed a female predominance, and had significantly higher cirrhosis rate, higher
      incidence of solitary tumors, lower incidence of infiltrative growth, higher
      proportion of marginal or exogenous growth, lower rate of portal vein invasion,
      and higher degree of differentiation. Median survival was longer in patients with
      BCS-associated HCC (76 months) than in those with HBV associated HCC (38 months).
      Of 38 patients with BCS-associated HCC, 22 patients who received combined surgery
      mainly by liver resection plus cavoatrial shunts exhibited hepatic venous outflow
      constriction relief, while the other 16 patients only underwent liver resection.
      The combined surgery group had significantly longer survival and lower incidences
      of post-operative lethal complications (P < 0.05). Multivariate analysis showed
      that relief of hepatic venous outflow obstruction was a protective factor for
      survival of patients with BCS-associated HCC, whereas portal vein invasion was a
      risk factor. CONCLUSIONS: BCS-associated HCC has a more favorable biological
      behavior and prognosis than HBV-associated HCC. For patients with BCS-associated
      HCC, tumor resection accompanied with relief of hepatic venous outflow
      obstruction can reduce the incidence of complications and extend survival.

PMID- 24112156
TI  - Assessment of the right and left ventricular function in patients with cor
      pulmonale using high-definition CT.
AB  - BACKGROUND: Cor pulmonale is often associated with changes of structure and
      function of the right ventricle (RV) and thus further affects functional changes
      of the left heart. Our study aimed to assess the left ventricular (LV) and RV
      function in patients with cor pulmonale using high-definition CT (HDCT). METHODS:
      We prospectively studied 18 cor pulmonale patients determined by the pulmonary
      function test, clinical examination, chest radiograph, electrocardiogram, and
      echocardiogram. The subject group was compared to a control group consisting of
      18 subjects. The RV and LV functions and RV myocardial mass (MM) were obtained by
      HDCT in the two groups. The results were compared between the two groups using
      the independent sample t test. Echocardiographic examination for cardiac function
      analysis was performed on the same day. RESULTS: The RV end-diastolic volume
      (EDV), RV end-systolic volume (ESV) and RV myocardial mass were significantly
      larger in the 18 cor pulmonale patients than in the control group (P < 0.05). The
      right ventricular ejection fraction (RVEF) was significantly lower in the 18 cor
      pulmonale patients than in controls (P < 0.01). The left ventricular EDV (LVEDV)
      and LVEF were significantly lower in cor pulmonale patients than in controls (P <
      0.01). There were strong correlations between MDCT and echocardiography, rRVEF =
      0.839 and rLVEF = 0.916, respectively. CONCLUSIONS: HDCT can accurately quantify
      RV and LV function. The right ventricular function is impaired in patients with
      cor pulmonale, while at the same time the left ventricular function is also
      impaired.

PMID- 24112157
TI  - Influence of sinomenine on protein profiles of peripheral blood mononuclear cells
      from ankylosing spondylitis patients: a pharmacoproteomics study.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory rheumatic
      disease which lacks satisfactory treatment so far. Sinomenine (SIN) is an
      alkaloid and has recently been utilized in treating multiple rheumatic diseases
      including AS in China, but its exact mechanism remains to be explored. This study
      investigated the alteration of proteome in peripheral blood mononuclear cells
      (PBMCs) from AS patients. METHODS: Thirty AS patients were enrolled in this
      study. PBMCs from each AS patient were cultured in medium with or without SIN
      respectively. Then PBMCs proteins from both groups were separated by two
      dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS). Two
      differentially expressed proteins were then chosen to be verified using Western
      blotting. RESULTS: Seven proteins, including a-synuclein (SNCA), calmodulin
      (CALM), acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A),
      chloride intracellular channel protein 1 (CLIC1), guanine nucleotide-binding
      protein G(I)/G(S)/G(T) subunit beta-1 (GNB1), gelsolin (GSN) and histone H2B type
      1-M (HISTH2BM) were over-expressed, while coronin- 1A (CORO1A) was under
      expressed in the SIN-treated PBMCs. Further bioinformatics search indicated that
      the changes of SNCA, ANP32A and CLIC1 pertained to apoptosis, while changes of
      GSN and CORO1A were associated with both apoptosis and inhibition of
      immunological function. Subsequently GSN and CORO1A were selected to validate by
      Western blotting and the results were consistent with those of 2-DE. CONCLUSION:
      There were 8 differentially expressed proteins in the SIN-treated PBMCs, which
      might shed some light on the mechanism of SIN in the treatment of AS.

PMID- 24112158
TI  - Changes in immunological function after treatment with transarterial
      chemoembolization plus radiofrequency ablation in hepatocellular carcinoma
      patients.
AB  - BACKGROUND: Different strategies for hepatocellular carcinoma (HCC) may have
      distinct effects on the immune system. The aim of this research was to
      investigate changes in the immunological function after transcatheter arterial
      chemoembolization (TACE) plus radiofrequency ablation (RFA) in HCC patients.
      METHODS: A total of 51 consecutive HCC treatment-naie patients was enrolled in
      this study and 20 healthy subjects served as controls. The therapeutic strategy
      was selected according to the tumor stage and general conditions. TACE was
      performed in 25 cases, TACE plus RFA in 17 and RFA in nine. All the patients
      underwent routine examinations and peripheral blood was harvested for the
      detection of lymphocyte subset by flow cytometry 1 day before, and 2 and 4 weeks
      after the treatment. The serum levels of alpha-fetoprotein (AFP), ALT and AST
      were also measured before and 4 weeks after treatment for the evaluation of
      therapeutic efficacy and liver function impairment. RESULTS: When compared with
      healthy controls, the CD4/CD8 ratio and the number of B cells and natural killer
      (NK) cells were significantly decreased in HCC patients before treatment (P <
      0.05). When compared with before treatment, the CD4+ cells and CD4/CD8 ratio
      decreased but CD8+ cells increased in the TACE group (P < 0.05); the CD4/CD8
      ratio and NK cells decreased but CD8+ cells increased in the TACE-RFA group (P <
      0.05); the CD3+ cells, CD4+ cells, CD4/CD8 ratio and NK cells increased in the
      RFA group (P < 0.05). Significant differences in the CD3+ cells, CD8+ cells,
      CD4/CD8 ratio and NK cells were observed among groups (P < 0.05). Moreover, the
      AFP level decreased and transaminase level increased in all groups (P < 0.05).
      Differences of pre and post treatment between groups were statistically
      significant (P = 0.016, 0.025, 0.018 respectively). CONCLUSIONS: Immunity was
      compromised in HCC patients; TACE and TACE plus RFA lowered immunologic function
      to a certain extent. RFA improved it accompanied by a protective effect on liver
      function.

PMID- 24112159
TI  - The relationship between serum amyloid A and apolipoprotein A-I in high-density
      lipoprotein isolated from patients with coronary heart disease.
AB  - BACKGROUND: Alteration in the protein composition of high-density lipoprotein
      (HDL) has been proposed as a mechanism for the development of coronary heart
      disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying
      the decrease in apolipoprotein A-I (apoA-I) has been found during the acute
      inflammation period. However, whether this phenomenon persists in CHD patients, a
      disease related to inflammation, is unknown. The purpose of the present study was
      to explore the relationship between SAA and apoA-I in HDL isolated from CHD
      patients. METHODS: Overall, 98 patients with confirmed stable CHD and 90 control
      subjects matched for age and gender were enrolled in this case-control study.
      Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate
      HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by
      enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear
      models were used in the analysis. RESULTS: Compared with controls, patients with
      CHD had a significant decrease in the amount of apoA-I ((14.21 +/- 8.44) ug/ml
      vs. (10.95 +/- 5.95) ug/ml, P = 0.003) in HDL and a significant increase in the
      amount of log SAA (1.21 +/- 0.46 vs. 1.51 +/- 0.55, P < 0.00001). Differences
      were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and
      other factors. An independently and statistically significant positive
      correlation between log SAA and apoA-I in HDL was observed only in the CHD group
      (beta = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age,
      age2, gender, BMI and HDL-C could explain a statistically significant 43% of the
      variance in apoA-I. CONCLUSIONS: This study provides direct evidence for the
      first time that there was an independent positive correlation between log SAA and
      apoA-I in the HDL of CHD patients, indicating the alteration of protein
      composition in HDL. However, the question of whether this alteration in HDL is
      associated with impairment of HDL functions requires further research.

PMID- 24112160
TI  - Clinical and radiographic predictors in diagnosing sputum smear-negative
      pulmonary tuberculosis in HIV-negative patients: a cross-sectional study in
      China.
AB  - BACKGROUND: In county-level tuberculosis (TB) dispensaries in China, the accurate
      diagnosis of sputum smear-negative pulmonary tuberculosis (SNPT) needs to be
      improved by developing and validating clinical and radiographic predictors.
      METHODS: The study was conducted simultaneously in three counties per province in
      Chongqing Municipality and Liaoning Province in China between May 2005 and May
      2006. A total of 432 new SNPT patients who are HIV-negative and more than 15
      years old diagnosed by expert panels in county-level TB dispensaries were
      recruited. Their sputum samples were collected for culture before anti-TB
      treatment, and the treatment outcomes (changes of X-rays) were followed up at the
      end of the 6th month. RESULTS: Of the 432 SNPT patients, sputum culture positive
      (9.7%) or culture negative with good changes of X-rays at the end of the 6th
      month (73.6%) was validated as SNPT. Four predictive variables were associated
      with validated SNPT in the multivariate logistic regression model: age <=55 years
      old (odds ratio (OR) 5.66; 95% CI 2.69-11.91), >60 days of cough (OR 3.73; 95% CI
      1.10-12.65), >=10% of pulmonary consolidation in the lungs (OR 5.40; 95% CI 2.90
      10.06), and pulmonary consolidation in the upper lobe anterior segment (OR 3.00;
      95% CI 1.57-5.72). The area under the receiver operating characteristic curve of
      the model was 0.77 (95% CI 0.71-0.83). CONCLUSION: Four predictors of clinical
      and radiological characteristics that had a good diagnostic performance of SNPT
      deserve to be recommended as index indicators of SNPT diagnosis in county-level
      TB dispensaries in China.

PMID- 24112161
TI  - Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor
      prognosis in stage N2 non-small cell lung cancer.
AB  - BACKGROUND: Patients with single station mediastinal lymph node (N2) non-small
      cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2.
      The molecular factors which are involved in disease progression remain largely
      unknown. The purpose of this study was to investigate gene expression differences
      between single station and multilevel N2 NSCLC and to identify the crucial
      molecular factors which are associated with progress and prognosis of stage N2
      NSCLC. METHODS: Gene expression analysis was performed using Agilent 4*44K Whole
      Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from
      single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse
      transcription (RT)-PCR was used to validate the differential expression of 14
      genes selected by cDNA microarray of which four were confirmed.
      Immunohistochemical staining for these validated genes was performed on formalin
      fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged
      in a high-density tissue microarray. RESULTS: We identified a 14 gene expression
      signature by comparative analysis of gene expression. Expression of these genes
      strongly differed between single station and multilevel N2 NSCLC. Four genes
      (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and
      real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC
      patients. Immunohistochemical staining for these genes in samples from 130 cases
      of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively
      correlated with overall survival of stage N2 NSCLC. CONCLUSIONS: Our results
      suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage
      N2 NSCLC. Further, CLDN1 and IGF2 may provide potential targeting opportunities
      in future therapies.

PMID- 24112162
TI  - Long-term outcome of correction of tetralogy of Fallot in 56 adult patients.
AB  - BACKGROUND: Although most patients with tetralogy of Fallot undergo radical
      repair during infancy and childhood, patients that remain undiagnosed and
      untreated until adulthood can still be treated. This study aimed to evaluate
      longterm outcomes of adult patients with tetralogy of Fallot who were treated
      surgically, and to determine the predictors of postoperative pulmonary
      regurgitation. METHODS: Fifty-six adult patients underwent complete surgical
      repair. Forty-three patients (76.8%) required a transannular patch. Systolic,
      diastolic, and mean pressure in the main pulmonary artery were measured after
      repair. RESULTS: The early mortality rate was 3.6%. The 16-year survival rate was
      (84.4 +/- 11.5)%. Late echocardiography revealed 41 patients with transannular
      patch who had pulmonary regurgitation, consisting of mild pulmonary regurgitation
      in 28 patients, moderate in eight, and severe regurgitation in five patients. In
      addition, there was right ventricular outflow tract stenosis in nine patients,
      moderate/severe tricuspid valve regurgitation in seven, and residual ventricular
      septal defect in five. Logistic regression analysis demonstrated that the mean
      pulmonary pressure measured just after repair predicted late pulmonary
      regurgitation. CONCLUSIONS: The long-term survival of surgically treated adult
      patients with tetralogy of Fallot is acceptable. The mean pressure >20 mmHg in
      the main pulmonary artery measured right after surgical repair may be a feasible
      reference to time the reconstruction of the pulmonary valve.

PMID- 24112163
TI  - Molecular subtypes identified by gene expression profiling in early stage
      endometrioid endometrial adenocarcinoma.
AB  - BACKGROUND: Early stage (FIGO stage I-II) endometrioid endometrial adenocarcinoma
      (EEA) is very common in clinical practice. However, patients with the early stage
      EEA show various clinical behaviors due to biological heterogeneity. Hence, we
      aimed to discover distinct classes of tumors based on gene expression profiling,
      and analyze whether the molecular classification correlated with the
      histopathological stages or other clinical parameters. METHODS: Hierarchical
      clustering was performed for class discovery in 28 early stage EEA samples using
      a special cDNA microarray chip containing 492 genes designed for endometrial
      cancer. Correlations between clinicopathologic parameters and our classification
      were analyzed. And the significance analysis of microarrays (SAM) array was used
      to identify the signature genes according to the tumor grade and myometrial
      invasion. RESULTS: Three tumor subtypes (subtypes I, II and III) were identified
      by hierarchical clustering, each subtype had different clinicopathological
      factors, such as tumor grade, myometrial invasion status, and FIGO stage.
      Moreover, SAM analysis showed 34 up-regulated genes in high grade tumors, and 38
      up-regulated genes and 1 down-regulated in deep myometrial invasive tumors. The
      overlap genes between these two high-risk factors were markedly up-regulated in
      subtype I, but down-regulated in subtype III. CONCLUSION: We have identified
      novel molecular subtypes in early stage EEA. Differential gene signatures
      characterize each tumor subtype, which could be used for recognizing the tumor
      risk and providing a basis for further treatment stratification.

PMID- 24112164
TI  - Risk factors associated with postoperative hospital stay after
      pancreaticoduodenectomy: a retrospective study.
AB  - BACKGROUND: Postoperative hospital stay after pancreaticoduodenectomy (PD) is
      relatively longer than after other gastrointestinal operations. The aim of the
      current study was to investigate the risk factors associated with prolonged
      hospital stay after PD. METHODS: Patients who had PD at the Cancer Hospital of
      Chinese Academy of Medical Sciences between December 2008 and November 2012 were
      selected for this retrospective study. Clinical and pathological data were
      collected and analyzed. The primary outcome was postoperative length of stay.
      Normal discharge or recovery was defined as a postoperative hospital stay of no
      more than 10 days; otherwise it was defined as delayed discharge or recovery
      (including hospital death). RESULTS: A total of 152 patients were enrolled in the
      present study. Postoperative hospital stay was (19.7 +/- 7.7) days (range 7-57).
      Of the 152 patients, 67 were discharged within the normal time and 85 had delayed
      discharge. Postoperative complications occurred in 62.5% (95/152), and the
      mortality rate was 3.29% (5/152). Multiple regression analysis showed that
      delayed discharge was significantly associated with postoperative complications
      (adjusted odds ratio (OR) 10.40, 95% confidence interval (CI) 3.58-30.22), age
      (adjusted OR 4.09, 95% CI 1.16-14.39), body mass index (BMI) (adjusted OR 4.40,
      95% CI 1.19-16.23), surgical procedure (adjusted OR 26.14, 95% CI 4.94-153.19),
      blood transfusion (adjusted OR 7.68, 95% CI 2.09-28.27), and fluid input
      (adjusted OR 3.47, 95% CI 1.24-11.57). CONCLUSIONS: Postoperative complications
      increase the time to postoperative hospital discharge. The length of hospital
      stay after PD is also associated with age, BMI, blood transfusion, surgical
      procedure, and fluid input. Further studies with more patients are needed in
      future.

PMID- 24112165
TI  - Genetic characterization and protein stability analysis of a Chinese family with
      Von Hippel-Lindau disease.
AB  - BACKGROUND: Von Hippel-Lindau disease (VHL), a heritable autosomal dominant
      disease characterized by neoplasia in multiple organ systems, has rarely been
      reported in Asia. We genetically investigated a unique Chinese family with VHL
      disease and performed an analysis of the VHL protein stability. METHODS: Genomic
      deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by
      polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of
      the Chinese family with VHL disease. PCR products were directly sequenced. We
      estimated the effects of VHL gene mutation on the stability of pVHL, which is
      indicated by the free energy difference between the wild-type and the mutant
      protein (DeltaDeltaG). RESULTS: The Chinese family was classified as VHL type 1.
      Three family members, including two patients and a carrier, had a T to G
      heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1. This
      missense mutation resulted in the transition from leucine to arginine in amino
      acid 101 of the VHL protein. There was low stability of the VHL protein (the
      DeltaDeltaG was 12.71 kcal/mol) caused by this missense mutation. CONCLUSIONS: We
      first reported a family with this VHL gene mutation in Asia. This missense
      mutation is predicted to significantly reduce the stability of the VHL protein
      and contribute to the development of the renal cell carcinoma (RCC) phenotype
      displayed by this family. The genetic characterization and protein stability
      analysis of families with VHL disease are important for early diagnosis and
      prevention of the disease being passed on to their offspring.

PMID- 24112166
TI  - Heterosexual transmission of HIV and related risk factors among serodiscordant
      couples in Henan province, China.
AB  - BACKGROUND: HIV transmission between discordant couples has become an important
      source of new infections in China. To describe the seroconversion rate among
      serodiscordant couples and to identify salient behavioral and clinical risk
      factors including ART that affect heterosexual HIV transmission risk among
      couples in rural China. METHODS: Longitudinal follow-up of an open cohort of HIV
      serodiscordant couples took place between 2007 and 2011 in Zhumadian, a city in
      southern Henan province in China, where blood plasma selling in 1990s led to a
      regional HIV epidemic. Annual follow-up included separate face-to-face interviews
      of husbands and wives, and HIV antibody testing for non-index partners. Cox
      proportional-hazard modeling was used to assess the relationship between HIV
      seroconversion and covariates of interest. RESULTS: By the end of 2011, 4499 HIV
      serodiscordant couples had been enrolled in at least two follow-up interviews;
      100 non-index partners seroconverted during the entire observation period for an
      incidence rate of 0.82 per 100 person-years (95% CI: 0.66-0.99). The incidence
      rates by the end of 2008, 2009, and 2010 were 2.14, 1.51, and 0.90 per 100
      personyears respectively. Always using condoms in the past year of sex, gender of
      the index partner, frequency of sex, and ART exposure were all significant
      predictors of HIV seroconversion in the negative spouse. ART was highly
      protective against seroconversion whether the index partner was actively
      receiving treatment at the last follow-up (RR = 0.05, 95% CI, 0.01-0.16) or if
      the index partner had ever received ART (RR = 0.01, 95% CI, 0.00, 0.12). The risk
      of seroconversion in the nonindex spouse also decreased the longer the duration
      of the index partner's exposure to ART. CONCLUSIONS: ART exposure and always
      using condom were highly protective against HIV seroconversion in the negative
      spouse. HIV incidence in serodiscordant couples has been decreasing over time,
      associated with ART treatment time within 7 years in the index partner. Gender of
      the index spouse and frequency of sex were also important predictors. Treatment
      as part of a combination prevention package may be a feasible method of HIV
      control in this population.

PMID- 24112167
TI  - Changes in anterior chamber depth following vitrectomy.
AB  - BACKGROUND: Anterior segment morphometry is crucial for ophthalmologists to
      understand the visual outcomes of cataract surgery, keratorefractive surgery, as
      well as some other anterior segment disorders. Previous reports in literature
      have shown that anterior chamber depth (ACD) may shift slightly after vitrectomy.
      This study aimed to characterize the shortterm changes in ACD in eyes after
      vitrectomy by means of A-scan ultrasound. METHODS: A prospective case series
      study was carried out on 29 eyes of 29 patients who underwent vitrectomy as the
      sole procedure. ACD was measured using A-scan ultrasound biometry shortly before
      vitrectomy and 1 week, 1 month, and 3 months after the surgery. Postoperative
      ACDs were compared with baseline. RESULTS: Twenty-nine patients (16 males and 13
      females) were enrolled in the study, with mean age of (50 +/- 11) (25-65) years.
      Twenty-three eyes of 23 patients were vitrectomized for vitreous hemorrhage (VH)
      and the other six were operated for idiopathic epiretinal membrane (ERM). The
      mean preoperative ACD of the VH eyes was (2.98 +/- 0.38) mm. No significant
      difference was found between the ACD of the VH eyes and their fellow eyes (P =
      0.058). The average preoperative ACD in the ERM eyes was (2.94 +/- 0.31) mm,
      which was statistically deeper than that of their fellow eyes ((2.85 +/- 0.28)
      mm, P = 0.008). No statistical difference was found in the postoperative average
      ACD of the VH eyes compared with baseline. In the ERM group, the postoperative
      ACD in the surgical eyes was still statistically deeper than the fellow eyes 1
      week after surgery (P = 0.034). However, such statistical difference disappeared
      at 1 or 3 months postoperative (P = 0.186 and 0.682). CONCLUSIONS: ERM may induce
      deepening of the ACD, which can be recovered by uneventful vitrectomy. VH does
      not cause shift of ACD, neither does vitrectomy.

PMID- 24112168
TI  - Prevalence of juvenile fibromyalgia syndrome in an urban population of Turkish
      adolescents: impact on depressive symptoms, quality of life and school
      performance.
AB  - BACKGROUND: Juvenile Fibromyalgia Syndrome (JFMS) is a chronic health condition
      characterized by widespread musculoskeletal pain and multiple tender points (TP).
      The objective of this study was to determine the prevalence of JFMS in the urban
      population of Samsun and to determine the impact of JFMS on depression symptoms,
      school performance and quality of life (QOL). METHODS: A cross-sectional study
      was conducted in 1109 children (mean age (14.8 +/- 2.0) years old). A
      questionnaire was applied to the children and a medical examination including TP
      was performed. Yunus and Masi's criteria were used for diagnosis of JFMS. The
      children with JFMS were compared with an age and sex matched non-JFMS group.
      Depression was assessed with Children's Depression Inventory (CDI) and QOL was
      evaluated with Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). RESULTS:
      Sixty-one (5.5%) (13 boys and 48 girls) of 1109 children met the diagnostic
      criteria of JFMS. While PedsQL scores of children with JFMS were lower than the
      non-JFMS group for physical, emotional, social, school functioning and total
      score (P = 0.001), CDI total score was higher in the JFMS group than in the non
      JFMS group (P = 0.001). The JFMS group reported more school absences (P = 0.001)
      and the average school grade was lower in the JFMS group than in the non-JFMS
      group (P = 0.03). CONCLUSION: The prevalence of JFMS is high in school age
      children. Since JFMS is a common problem of childhood, early diagnosis and
      identification of the disorder and more comprehensive and successful treatment
      approaches with appropriate psychological assistance may prevent more complex and
      severe problems in adulthood.

PMID- 24112169
TI  - Switching from morphine to fentanyl attenuates the decline of u-opioid receptor
      expression in periaqueductal gray of rats with morphine tolerance.
AB  - BACKGROUND: Opioid switching is a therapeutic maneuver to improve analgesic
      response and/or reduce adverse side effects although the underlying mechanisms
      remain unknown. The u-opioid receptor (MOR) has an important role in mediating
      the actions of morphine and other analgesic agents. This study is aimed at
      exploring the changes of MOR in the periaqueductal gray (PAG) in rats when
      morphine is substituted for equianalgesic fentanyl. METHODS: Forty rats were
      randomly assigned to five treatment groups: 7 days normal saline group (N group),
      7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine
      and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM
      group). Rats repeatedly received subcutaneous injections of morphine sulfate (10
      mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats'
      antinociceptive response to thermal pain was evaluated by the tail flick latency
      assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and
      Western blotting analyses respectively. RESULTS: This study showed that after
      morphine was substituted with fentanyl on day 8, the tail flick latency (TFL)
      increased from (3.9 +/- 0.4) seconds to (11.4 +/- 0.4) seconds. The results also
      demonstrated that both MOR mRNA and protein expression in the PAG of rats in the
      MF group were less than that in the M group (P < 0.05) but more than that in MM
      group (P < 0.05). CONCLUSIONS: Equianalgesic fentanyl was still antinociceptive
      effective in rats with morphine tolerance, which may be due to the switching from
      morphine to fentanyl attenuating the decline of MOR expression in the PAG of
      rats.

PMID- 24112170
TI  - Multimodality imaging assessments of response to metformin therapy for breast
      cancer in nude mice.
AB  - BACKGROUND: Metformin is the most widely used anti-diabetic drug in the world. An
      increasing body of evidence shows metformin also blocks cell cycle progression
      and selectively induces apoptosis via caspase activation in some breast tumor
      cells. Diffusion-weighted imaging (DWI) and bioluminescence imaging (BLI) have
      great potential in the evaluation of the early response to cancer therapies. We
      used DWI and BLI in evaluating the response of breast cancer to metformin.
      METHODS: The luciferase-engineered human breast cancer cell line MDA-MB-231 was
      inoculated into the mammary fat pad of nude mice. Twelve female nude mice bearing
      tumors were divided into two groups. The mice in the treatment group received
      metformin (2 mg/ml in drinking water daily) after tumor inoculation, and the mice
      in the control group were offered drinking water without any drug added. We
      performed 7T magnetic resonance imaging and optical imaging every week. Imaging
      included T1- and T2-weighted imaging, DWI, and BLI. After imaging. The tumors
      were collected and subjected to histological analysis. RESULTS: The mean
      photons/second of tumors in the treatment group was (3.00 +/- 0.43)* 10(6) at day
      one, (1.01 +/- 0.14)* 10(7) at 2 weeks, (5.79 +/- 1.42)* 10(7) at 4 weeks, and
      (2.33 +/- 0.70)* 10(7) at 8 weeks. The mean photons/second of tumors in the
      control group was (3.29 +/- 0.59)* 10(6) at day one, (3.59 +/- 0.63)* 10(7) at 2
      weeks, (3.87 +/- 0.56)* 10(8) at 4 weeks, and (4.12 +/- 1.72)* 10(8) at 8 weeks.
      Compared to the control group, the treatment group showed an obvious decrease in
      the mean bioluminescence (photons/s) of the tumors and fewer metastases.
      Histological examination confirmed the presence of fewer metastases. DWI showed
      the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value
      was (0.9287 +/- 0.04346)* 10(-3) mm(2)/s in the treated tumors and (0.7553 +/-
      0.01804)* 10(-3) mm(2)/s in the untreated tumors. The ADC value of tumors in the
      treatment group was significantly higher than the control tumors (P = 0.0013).
      CONCLUSIONS: The growth and metastasis of MDA-MB-231 breast cancer may be
      inhibited by metformin. DWI and BLI have great potentials in the evaluation of
      the early response to metformin treatment. BLI has a high degree of sensitivity
      and is able to detect micrometastasis, thus can be used for identifying tumor
      metastasis in vivo.

PMID- 24112171
TI  - Inactivation of the Rho-ROCK signaling pathway to promote neurologic recovery
      after spinal cord injuries in rats.
AB  - BACKGROUND: After injury, axonal regeneration of the adult central nervous system
      (CNS) is inhibited by myelin-derived growth-suppressing proteins. These axonal
      growth inhibitory proteins are mediated via activation of Rho, a small GTP
      binding protein. The activated form of Rho, which is bound to GTP, is the direct
      activator of Rho kinase (ROCK) through serial downstream effector proteins to
      inhibit axonal regeneration. The objective of this study was to observe the
      therapeutic effect of inactivation of the Rho-ROCK signaling pathway to promote
      neurologic recovery after spinal cord injuries in rats. METHODS: One hundred and
      twenty adult female Sprague-Dawley rats were randomly divided into three groups.
      Laminectomies alone were conducted in 40 rats in the sham group. Laminectomies
      and spinal cord transections were performed in 40 rats in the control group
      (treated with normal saline administered intraperitoneally). Laminectomies and
      spinal cord transections were performed in 40 rats in the fasudil-treated group
      (treated with fasudil administered intraperitoneally). Neurologic recovery was
      evaluated before surgery and 3 days, and 1, 2, 3, and 4 weeks after surgery using
      the Basso-Beattie-Bresnahan (BBB) scale of hind limb movement. At the same time,
      the expression of RhoA mRNA was determined with RT-PCR. Histopathologic
      examinations and immunofluorescence staining of NF were performed 1 month after
      surgery. RESULTS: Compared with the control group, the BBB scores of the fasudil
      treated group were significantly increased and the expression of RhoA mRNA was
      significantly decreased. In the fasudil-treated group, a large number of NF
      positive regenerating fibers was observed; some fibers crossed the slit of the
      lesion. CONCLUSION: Inactivation of the Rho-ROCK signaling pathway promotes CNS
      axonal regeneration and neurologic recovery after spinal cord injuries in rats.

PMID- 24112172
TI  - Inhibitory effect of iron on in vitro proliferation of smooth muscle cells.
AB  - BACKGROUND: Iron is a biocorrodible metal that might be used in bioabsorbable
      stents. This study investigated the effects at the cellular and protein levels of
      soluble divalent iron (ferrous gluconate) and soluble trivalent iron (ferric
      chloride) on the proliferation of human aortic smooth muscle cell (HASMC) in
      vitro. METHODS: The water-soluble tetrazolium (WST-1) test was used to evaluate
      the effect of iron on proliferation of HASMC and Western blotting was used to
      measure the levels of signaling proteins involved in proliferative and apoptosis
      pathways. RESULTS: HASMC proliferation was inhibited in a concentration dependent
      manner after treatment with soluble divalent and trivalent iron at concentrations
      of 100-500 umol/L. Western blotting analysis showed that the proliferating cell
      nuclear antigen (PCNA) expression following treatment with soluble divalent iron
      and trivalent iron at 100, 300 and 500 umol/L was reduced compared to the
      control. The PCNA expression decreased with increasing iron concentration and to
      a greater extent with the trivalent iron than with the divalent iron treatment
      group. The p53 expression was markedly increased in a concentration dependent
      manner in both iron treatment groups. CONCLUSION: The soluble divalent iron and,
      to a greater degree trivalent iron, inhibited HASMC proliferation in a
      dosedependent manner, which may be attributed to reduction of PCNA expression and
      increase of p53 expression.

PMID- 24112173
TI  - Combination of (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography and magnetic resonance imaging is an optimal way to evaluate
      rheumatoid arthritisin rats dynamically.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune
      inflammatory disorder. Many methods have been used to observe the progress of RA.
      The purpose of this study was to observe the progress of RA in rats with 18F
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the
      relationships among different methods in evaluation of RA. METHODS: Sixteen
      healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA
      group and a control group. Bovine type II emulsified incomplete Freud's adjuvant
      was used to induce arthritis in the RA group. Arthritis score of the rats in two
      groups were recorded, and (18)F-FDG PET/CT, MR imaging were performed both on the
      corresponding rats every 3 days. All the rats were sacrificed at week 5, and
      histopathological examination was performed on rat knees stained with
      haematoxylin and eosin. RESULTS: The arthritis score and the standard uptake
      value (SUV) of knee joints in RA rats increased with the progression of arthritis
      gradually. Both peaks of arthritis score and SUV appeared at 21 days after the
      first immune injection, then the arthritis score and SUV of knee joints decreased
      slowly. The arthritis scores of knee joints in RA rats were positively correlated
      with their SUV changes. The MR images were confirmed by the histopathological
      studies. CONCLUSION: PET/CT can detect the earliest molecular metabolism changes
      of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all
      of which indicated that PET/CT and MR imaging may be applied as useful tools to
      monitor the progress of RA.

PMID- 24112174
TI  - Proliferative and apoptotic effects of andrographolide on the BGC-823 human
      gastric cancer cell line.
AB  - BACKGROUND: Andrographolide has been shown to have anticancer activity on diverse
      cancer cell lines representing different types of human cancers. The aim of this
      research was to investigate the anticancer and apoptotic effects of
      andrographolide on the BGC-823 human gastric cancer cell line. METHODS: Cell
      proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with
      flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining
      assay, and morphologic structure with transmission electron microscopy.
      Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2,
      Bax, and caspase-3 expressions. RESULTS: Andrographolide showed a time- and
      concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to
      controls, the number of cells in the G0-G1-phase increased significantly, S and
      G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and
      both early and late apoptotic rates increased significantly compared to the
      controls, all in a concentration-dependent manner. Bax and caspase-3 expressions
      were markedly increased, and Bcl-2 expression was decreased. CONCLUSIONS:
      Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis
      by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2
      expression. Andrographolide may be useful as a potent and selective agent in the
      treatment of human gastric cancers.

PMID- 24112176
TI  - No association between cytochrome P450 2D6 gene polymorphism and risk of acute
      leukemia: evidence based on a meta-analysis.
AB  - BACKGROUND: Many studies indicated the human cytochrome P450 2D6 (CYP2D6) gene
      polymorphism was associated with acute leukemia (AL) susceptibility, however, the
      results were inconsistent. So we performed this meta-analysis to evaluate the
      relationship between CYP2D6*3 or CYP2D6*4 polymorphism and AL susceptibility.
      METHODS: We searched PubMed database up to February 20, 2013, and finally yielded
      9 case-control studies including 1343 cases and 1843 controls which tested the
      association between CYP2D6*3 or *4 polymorphism and AL. After data extraction, we
      conducted a meta-analysis using the Comprehensive Meta Analysis software.
      RESULTS: Overall, no significant association between CYP2D6*3 or *4 polymorphism
      and AL risk was found in this metaanalysis (+ vs. -: OR = 1.13, 95% CI = 0.79
      1.63; +/+ vs. -/-: OR = 1.73, 95% CI = 0.99-3.02; -/+ vs. -/-: OR = 1.03, 95% CI
      = 0.68-1.56; (-/+ and +/+) vs. -/-: OR = 1.08, 95% CI = 0.72-1.63; +/+ vs. (-/+
      and -/-): OR = 1.76, 95% CI = 0.98-3.17). Similar results were also been found in
      stratified subgroup analysis. There was no publication bias. CONCLUSION: CYP2D6*3
      or *4 polymorphism might not be associated with AL susceptibility. However, the
      results need to be further confirmed by well-designed and high quality randomized
      controlled trials with larger sample sizes.

PMID- 24112175
TI  - Epidemiology of methicillin-resistant Staphylococcus aureus infection and
      empirical antibiotic therapy for MRSA infection: multicenter investigation.
AB  - BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus
      (MRSA) maybe changed by strict infection control measures, and the impact of
      empirical antibiotic therapy on the outcomes of MRSA infection was not clear. We
      aimed to investigate the present epidemiological status of MRSA infection and
      empirical antibiotic therapy for MRSA infection in university teaching hospitals
      in mainland China. METHODS: The present study was a multicenter prospective
      observational study conducted in five university teaching hospitals. Patients who
      were consecutively admitted to the intensive care unit and signed a consent form
      from March 3, 2011 to May 31, 2011 were included. Patients with age <18 years or
      with a length of hospital stay <48 hours were excluded from this study. The
      following variables were collected or recorded: demographic data, general status,
      APACHE II score of the patient at the time of admission, infections, and the use
      of antibiotics during a stay. Primary outcomes and prognostic indicators included
      length of hospital stay and 28-day and 90-day mortality. The differences between
      the patients with appropriate empirical therapy and patients with inappropriate
      therapy were analyzed to detect the influences of antibiotic therapy on the
      prognosis of MRSA infection. RESULTS: A total of 682 cases were enrolled. Thirty
      (66.2%) of 88 MRSA cases were treated with effective antibiotics for MRSA
      infection; only 20% received appropriate empirical antibiotic treatment. The
      empirical therapy group compared with the target therapy group had a shorter
      length of stay, but there were no significant differences in mortality rates.
      There were no significant differences in the length of hospital stay, length of
      stay, and 28-day and 90-day mortality between MRSA-infected patients who received
      or not received effective antibiotics. Two hundred and eighteen cases received
      sensitive antibiotics for MRSA. CONCLUSIONS: The MRSA infection rates are at
      relatively low levels in university teaching hospitals in China. The empirical
      use of sensitive antibiotics for MRSA infection was at relatively high rate, and
      there is a tendency of overusing in patients without MRSA infection. On the other
      hand, the rate of appropriate empirical antibiotic therapy for patients with MRSA
      infection is relatively low.

PMID- 24112177
TI  - Effects of glucocorticoids on traumatic brain injury related critical illness
      related corticosteroid insufficiency.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a heterogeneous condition that can
      lead to critical LLLness-related corticosteroid insufficiency (CIRCI) causing a
      high mortality and morbidity. Glucocorticoids were widely used in the clinical
      management of TBI, but their benefit has been challenged in some studies and
      their efficacy, especially for treating CIRCI in TBI patients, remains unclear.
      METHODS: We conducted a meta-analysis of published data to determine if the
      controversy is related to clinical dosing and timing of glucocorticoids (GCs)
      application. We analyzed published reports in four databases (MEDLINE, EMBASE,
      the Cochrane Controlled Trials Register, and CBMdisc). The published data were
      stratified into not only low- and high-dose GCs group but also short- and long
      term GCs group to compare their effectiveness in improving TBI outcomes. RESULTS:
      We totally identified 16 reports. For low-dose patients, the pooled relative
      risks (RRs) for two clinical outcomes of death or a combination of death and
      severe disability were 0.95 (95% confidence interval (CI): 0.80 to 1.13) and 0.95
      (95% CI: 0.83 to 1.09), respectively. The risks for infection and
      gastrointestinal bleeding were 0.85 (95% CI: 0.50 to 1.45) and 0.64 (95% CI: 0.15
      to 2.70), respectively. For high-dose group, the pooled RR of death is 1.14 (95%
      CI: 1.06 to 1.21). The pooled RRs for infection and gastrointestinal bleeding for
      the high-dose patients were 1.04 (95% CI: 0.93 to 1.15) and 1.26 (95% CI: 0.92 to
      1.75), respectively. For long-term use group, the pooled RRs for two clinical
      outcomes of death or a combination of death and severe disability were 0.98 (95%
      CI: 0.87 to 1.12) and 1.00 (95% CI: 0.90 to 1.11), respectively. The risks for
      infection and gastrointestinal bleeding were 0.88 (95% CI: 0.71 to 1.11) and 0.96
      (95% CI: 0.35 to 2.66), respectively. For short-term use group, the pooled RR of
      death is 1.15 (95% CI: 1.07 to 1.23), and importantly the effects on infections
      were beneficial in terms of TBI patients suffering from CIRCI. CONCLUSIONS: This
      meta-analysis suggests an increased risk of death for TBI patients on a high dose
      and short term of glucocorticoids compared with those on a low dose and long
      term, for whom a trend towards clinical improvement is evident. In addition,
      stress-does of GCs further decrease the pneumonia incidence in TBI patients
      suffering from CIRCI. A large-scale multicenter randomized controlled trial is
      warranted for testing (1) the efficacy of stress-dose GCs treatment in the sub
      acute phase of TBI (4-21 days after initial trauma), when CIRCI is most likely to
      occur; (2) the hypothesis that stress-dose GCs could boost patients' stress
      function and ensure survival.

PMID- 24112178
TI  - Impact of prosthesis-patient mismatch on survival after mitral valve replacement:
      a systematic review.
AB  - OBJECTIVE: To determine whether the prosthesis-patient mismatch has a deleterious
      impact on survival after mitral valve replacement. DATA SOURCES: A comprehensive
      literature search of PubMed, Embase, and ScienceDirect was carried out.
      References and cited papers of relevant articles were also checked. STUDY
      SELECTION: All articles published after January 1980 was initially considered.
      Non-English and non-human studies, case reports, and reviews were excluded from
      the initial search. References and cited papers of relevant articles were also
      checked. RESULTS: A total of 8 retrospective cohort studies were identified for
      this review. The overall incidence of prosthesis-patient mismatch (<1.3 to <1.2
      cm(2)/m(2)) after mitral valve replacement ranged from 3.7% to 85.9% (moderate
      prosthesis-patient mismatch (0.9 to 1.2 cm(2)/m(2)) in 37.4% to 69.5%, severe
      prosthesis-patient mismatch (<0.9 cm(2)/m(2)) in 8.7% to 16.4%). Four studies
      demonstrated an association of prosthesis-patient mismatch with reduced long-term
      survival, but the other four studies found no significant deleterious impact of
      prosthesis-patient mismatch after mitral valve replacement. No definite
      conclusion could be derived from these conflicting results. CONCLUSIONS: Current
      evidence is insufficient to derive a definite conclusion whether mitral
      prosthesis-patient mismatch affects long-term survival because of the biases and
      confounding factors that interfere with late clinical outcomes. Goodquality
      prospective studies are warranted to evaluate the impact of mitral prosthesis
      patient mismatch after mitral valve replacement in the future.

PMID- 24112179
TI  - Interventions to improve chronic cyclosporine A nephrotoxicity through inhibiting
      renal cell apoptosis: a systematic review.
AB  - OBJECTIVE: To reveal interventions for chronic cyclosporine A nephrotoxicity
      (CCN) and provide new targets for further studies, we analyzed all relevant
      studies about interventions in renal cell apoptosis. DATA SOURCES: We collected
      all relevant studies about interventions for cyclosporine A (CsA)-induced renal
      cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI
      (1986 to July 2010), evaluated their quality, extracted data following PICOS
      principles and synthesized the data. STUDY SELECTION: We included all relevant
      studies about interventions in CsA-induced renal cell apoptosis no limitation of
      research design and language) and excluded the duplicated articles, meeting
      abstracts and reviews without specific data. RESULTS: There were three kinds of
      intervention, include anti-oxidant (sulfated polysaccharides, tea polyphenols,
      apigenin, curcumin, spirulina, etc), biologics (recombinant human erythropoietin
      (rhEPO), a murine pan-specific transforming growth factor (TGF)-beta-neutralizing
      monoclonal antibody1D11, cartilage oligomeric matrix protein (COMP)-angiopoietin
      1 and hepatocyte growth factor (HGF) gene), and other drugs (spironolactone,
      rosiglitazone, pirfenidone and colchicine). These interventions significantly
      improved the CCN, renal cell apoptosis and renal dysfunction through intervening
      in four apoptotic pathways in animals or protected renal cells from apoptosis
      induced by CsA and increased cell survival through respectively four pathways in
      vitro. CONCLUSIONS: There are three group interventions for CCN. Especially anti
      oxidant drugs can significantly improve CCN, renal cell apoptosis and renal
      dysfunction. Many drugs can improve CCN through intervening in Fas/Fas ligand or
      mitochondrial pathway with sufficient evidences. Angiotensin II, nitric oxide
      (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.

PMID- 24112180
TI  - Farnesoid X receptor in the study of fibrosis and its treatments.

PMID- 24112181
TI  - Podocyte-related proteins in membranous nephropathy progression.

PMID- 24112182
TI  - Clinical experience with multiple stents in complex thoracoabdominal aortic
      aneurysms.

PMID- 24112183
TI  - CRABP2 and FABP5 identified by 2D DIGE profiling are upregulated in human bladder
      cancer.

PMID- 24112184
TI  - Safety of convalescent sera for the treatment of viral severe acute respiratory
      syndrome: an experimental model in rhesus macaque.

PMID- 24112185
TI  - Modified trabeculotomy for primary congenital glaucoma.

PMID- 24112186
TI  - Chorea in a Chinese adult after pulmonary endarterectomy with deep hypothermia
      and circulatory arrest.

PMID- 24112187
TI  - Catheter-directed intervention and thrombolysis for the treatment of massive
      pulmonary embolism that caused cardiac arrest.

PMID- 24112188
TI  - Leprosy presented as cutaneous erythema.

PMID- 24112189
TI  - Air embolism after deflation of the pneumoperitoneum in fast-track laparoscopic
      assisted hemicolectomy.

PMID- 24112190
TI  - Postoperative heterotopic mesenteric and incision ossification.

PMID- 24112191
TI  - The necessary to formulate the definition and specifications for the palliative
      treatment of advanced glioma.

PMID- 24112192
TI  - Anticholinergic drug burden in older people's brain - how well is it measured?
AB  - Concurrent use of several drugs with potential anticholinergic properties is
      highly prevalent in the elderly. Methods to determine the overall anticholinergic
      drug burden have been developed to estimate the risk of central anticholinergic
      adverse effects. The objective of this MiniReview was to critically appraise the
      clinical utility of the methods used to assess the anticholinergic drug burden in
      older people's brain. We evaluated the in vitro method used to measure the
      anticholinergic activity in a patient's serum and the four anticholinergic drug
      scales: Anticholinergic Risk Scale, Anticholinergic Cognitive Burden, Drug Burden
      Index and Anticholinergic Drug Scale. Medline searches of the literature from
      January 1988 to January 2013 were performed. Studies that related anticholinergic
      drug burden to central adverse outcomes in elderly people were included, while
      case reports and studies of single substances were excluded. Despite the
      consistently reported association between a high anticholinergic drug burden and
      negative cognitive and psychomotor outcomes in older patients, there are
      discrepancies in the literature. Furthermore, no significant cognitive
      improvements after the anticholinergic drug burden was reduced have been shown in
      randomized controlled trials. It is reasonable to question whether the estimated
      anticholinergic drug burden can predict the overall brain effects of multiple
      anticholinergic agents in older people. 

PMID- 24112194
TI  - The Cost of Canine Rabies on Four Continents.
AB  - We estimated the economic impacts of canine rabies in Latin America, Africa and
      Asia. Direct and indirect costs of rabies post-exposure prophylaxis, dog
      vaccination and control, rabies diagnostic testing and cattle mortality-related
      costs were accounted for. The number of human deaths was updated from previous
      estimates based on population growth, and the costs associated with the risk of
      human mortality were incorporated. We accounted for uncertainty associated with
      the parameter estimates using a Monte Carlo simulation and estimated that the
      global burden of canine rabies is approximately $124 billion annually. This
      result illustrates the potential benefits that could be realized if canine rabies
      was eliminated and provides an important benchmark against which the cost of any
      potential elimination campaign can be compared. 

PMID- 24112193
TI  - Oral administration of the flavanol (-)-epicatechin bolsters endogenous
      protection against focal ischemia through the Nrf2 cytoprotective pathway.
AB  - Consumption of flavan-3-ols, notably (-)-epicatechin (EC), has been highly
      recommended in complementary and alternative medicine (CAM) due to reports that
      flavan-3-ols boost antioxidant activity, support vascular function, and prevent
      cardiovascular disease. To date, in vivo efficacy and mechanisms of action for
      many CAM therapies, including EC, remain elusive in brain ischemia. In contrast
      to its purported direct antioxidant role, we hypothesized protection through
      activation of the endogenous transcriptional factor Nrf2. To screen cellular
      protection and investigate Nrf2 activation, we adopted a pretreatment paradigm
      using enriched primary neuronal cultures from mice and washed out EC prior to
      oxygen glucose deprivation to attenuate direct antioxidant effects. EC protected
      primary neurons from oxygen glucose deprivation by increasing neuronal viability
      (40.2 +/- 14.1%) and reducing protein oxidation, effects that occurred
      concomitantly with increased Nrf2-responsive antioxidant protein expression. We
      also utilized wildtype and Nrf2 C57BL/6 knockout mice in a permanent model of
      focal brain ischemia to evaluate glial cell regulation and complex sensorimotor
      functioning. EC-treated wildtype mice displayed a reduction or absence of
      forelimb motor coordination impairments that were evident in vehicle-treated
      mice. This protection was associated with reduced anatomical injury (54.5 +/-
      8.3%) and microglia/macrophage activation/recruitment (56.4 +/- 13.0%). The
      protective effects elicited by EC in both model systems were abolished in tissues
      and neuronal cultures from Nrf2 knockout mice. Together, these data demonstrate
      EC protection through Nrf2 and extend the benefits to improved performance on a
      complex sensorimotor task, highlighting the potential of flavan-3-ols in CAM
      approaches in minimizing subsequent stroke injury. 

PMID- 24112195
TI  - The effects of deliberate practice and feedback to teach standardized handoff
      communication on the knowledge, attitudes, and practices of first-year residents.
AB  - BACKGROUND: Residents' shift length reduction and communication errors in
      transitions of care necessitate educating residents on handoff communication.
      PURPOSE: We examined the change in knowledge, attitudes, and practices of 1st
      year residents after implementing a curriculum using deliberate practice to teach
      handoff communication. METHODS: First-year residents completed a needs assessment
      survey and a video assessment of handoff practices. They participated in a brief
      curriculum using lecture and deliberate practice with feedback to teach a
      standardized approach to handoff communication. Change in knowledge, attitudes,
      and practices were measured with survey and video assessments. RESULTS: Eleven
      1st-year residents completed the course and final assessments. Residents' comfort
      with performing handoffs and their perceived efficiency indicated improvement.
      Practices improved, with increased inclusion of important features of handoffs
      (6.31 to 7.64, p < .001). CONCLUSIONS: A brief curriculum utilizing deliberate
      practice is an effective way to improve handoff practices of 1st-year residents.

PMID- 24112196
TI  - Integrating medical students' goals, self-assessment and preceptor feedback in an
      ambulatory clerkship.
AB  - BACKGROUND: Self-assessment and feedback are important elements for improving
      performance. However, coordinating their content remains elusive. PURPOSE: The
      purpose is to determine whether student self-assessment and preceptor feedback
      correlate with course outcomes and whether preceptor feedback informs student
      self-assessment. METHODS: Our students generate initial and midterm goals and
      preceptors provide midterm feedback. We coded goals and feedback as clinical
      subsets, knowledge, career oriented, and attitudinal. We assessed associations
      with exams and evaluations using correlations, chi-square, and comparisons of
      means. RESULTS: Students usually listed clinical goals (72%), whereas preceptors
      noted attitudes (50%). Students' self-assessments had little association with
      exams, evaluations, or preceptor feedback. Students cited by preceptors for
      clinical strengths scored higher on exams (77.2 vs. 72.7, p < .01). Those cited
      for knowledge received more honors and high pass (78 vs. 60%, p = .05)
      evaluations. CONCLUSIONS: Students and preceptors emphasize different aspects of
      performance. Student self-assessments were not associated with outcomes, but
      preceptor feedback was. Student self-assessment seemed resistant to feedback.

PMID- 24112197
TI  - Mobile technology for the facilitation of direct observation and assessment of
      student performance.
AB  - BACKGROUND: We developed, implemented, and assessed a web-based clinical
      evaluation application (i.e., CEX app) for Internet-enabled mobile devices,
      including mobile phones. The app displays problem-specific checklists that
      correspond to training problems created by the Clerkship Directors in Internal
      Medicine. PURPOSE: We hypothesized that use of the CEX app for directly observing
      students' clinical skills would be feasible and acceptable, and would demonstrate
      adequate reliability and validity. METHODS: Between July 2010 and February 2012,
      266 third-year medical students completed 5 to 10 formative CEXs during their
      internal medicine clerkship. The observers (attendings and residents), who
      performed the CEX, used the app to guide and document their observations, record
      their time observing and giving feedback to the students, and their overall
      satisfaction with the CEX app. Interrater reliability and validity were assessed
      with 17 observers who viewed 6 videotaped student-patient encounters, and by
      measuring the correlation between student CEX scores and their scores on
      subsequent standardized-patient Objective Structured Clinical Examination (OSCE)
      exams. RESULTS: A total of 2,523 CEXs were completed by 411 observers. The
      average number of evaluations per student was 9.8 (+/- 1.8 SD), and the average
      number of CEXs completed per observer was 6 (+/- 11.8 SD). Observers spent less
      than 10 min on 45.3% of the CEXs and 68.6% of the feedback sessions. An
      overwhelming majority of observers (90.6%) reported satisfaction with the CEX.
      Interrater reliability was measured at 0.69 among the observers viewing the
      videotapes, and their ratings discriminated between competent and noncompetent
      performances. Student CEX grades, however, did not correlate with their end of
      3rd-year OSCE scores. CONCLUSIONS: The use of this CEX app is feasible and it
      captures students' clinical performance data with a high rate of user
      satisfaction. Our embedded checklists had adequate interrater reliability and
      concurrent validity. The grades measured on this app, however, were not
      predictive of subsequent student performance.

PMID- 24112198
TI  - Long-term gain after team-based learning experience in a pediatric clerkship.
AB  - BACKGROUND: Team-based learning (TBL) increases student engagement, value of
      teamwork, and performance on standardized evaluations. PURPOSE: The authors
      implemented a 3rd-year pediatric TBL curriculum, evaluating its effect on
      satisfaction, engagement, value of teamwork, and short-term and long-term
      academic performance. METHOD: Students evaluated the TBL curriculum and core
      lectures through satisfaction, engagement and value of team surveys. Scores on
      short-term and long-term examinations were compared to historical data. RESULTS:
      The first implementation year, students were less likely to enjoy TBL sessions
      compared to lectures. The 2nd year, this difference lessened. Through both years,
      students reported dramatic increases in classroom engagement during TBL compared
      to lecture. Students developed a greater value for teams after participating in
      TBL. Short-term and long-term examination scores improved significantly.
      CONCLUSIONS: Both short-term and long-term performance improved with
      implementation of TBL, emphasizing the benefits of a curriculum that allows
      students to critically engage with material.

PMID- 24112199
TI  - Medical Spanish programs in the United States: a critical review of published
      studies and a proposal of best practices.
AB  - BACKGROUND: Despite an increasing demand for medical Spanish training, there has
      never been a comprehensive review of the methodology and outcomes of existing
      programs. PURPOSE: This article critically reviews studies published about
      medical Spanish education and proposes best practices for curriculum design and
      program research and evaluation. METHODS: The authors reviewed articles published
      on medical Spanish programs in the United States from 1977 to 2012, then
      appraised them for the presence of five factors commonly used in second-language
      acquisition (SLA) research. RESULTS: Only 2 of 23 published studies of programs
      met all 5 criteria. There was high variability in design and infrequent use of
      valid and reliable outcome measures. No consensus emerged as to best practices.
      Instead, reported outcomes were often inadequate surrogate markers for desired
      educational outcomes in interactions with Spanish speakers. CONCLUSIONS: There is
      a significant need for effective medical Spanish programs based on solid SLA
      principles and research methods.

PMID- 24112200
TI  - Human dimensions in bedside teaching: focus group discussions of teachers and
      learners.
AB  - BACKGROUND: Clinical teaching has moved from the bedside to conference rooms;
      many reasons are described for this shift. Yet, essential clinical skills,
      professionalism, and humanistic patient interactions are best taught at the
      bedside. PURPOSE: Clinical teaching has moved from the bedside to conference
      rooms; many reasons are described for this decline. This study explored
      perceptions of teachers and learners on the value of bedside teaching and the
      humanistic dimensions of bedside interactions that make it imperative to shift
      clinical teaching back to the bedside. METHOD: Focus group methodology was used
      to explore teacher and learner opinions. Four teacher groups consisted of (a)
      Chief Residents, (b) Residency Program Directors, (c) skilled bedside teachers,
      and (d) a convenience group of other Department of Medicine faculty at Boston
      University School of Medicine. Six learner groups consisted 2 each of 3rd-year
      students, PGY1 medicine residents, and PGY2 medicine residents. Each discussion
      lasted 60 to 90 minutes. Sessions were audiotaped, transcribed, and analyzed
      using qualitative methods. RESULTS: Teachers and learners shared several opinions
      on bedside teaching, particularly around humanistic aspects of bedside
      interactions. The key themes that emerged included (a) patient involvement in
      discussions, (b) teachers as role models of humanism, (c) preserving learner
      autonomy, (d) direct observation and feedback of learners at the bedside, (e)
      interactions with challenging patients, and (e) admitting limitations. Within
      these themes, participants noted some behaviors best avoided at the bedside.
      CONCLUSIONS: Teachers and learners regard the bedside as a valuable venue in
      which to learn core values of medicine. They proposed many strategies to preserve
      these humanistic values and improve bedside teaching. These strategies are
      essential for true patient-centered care.

PMID- 24112201
TI  - A tiered mentorship program improves number of students with an identified
      mentor.
AB  - BACKGROUND: Mentorship is critical to professional development and academic
      success. Unfortunately, only about 40% of medical students can identify a mentor.
      While group mentorship has been evaluated - the concept of a specialty specific,
      tiered group mentorship program (TGMP) has not. In the latter, each member of the
      group represents a unique education or professional level. PURPOSE: The purpose
      of this study was to investigate the ability of a specialty-specific, tiered
      group mentorship program to improve mentorship for students interested in
      emergency medicine. METHODS: Groups consisted of faculty members, residents, 4th
      year students pursuing a career in Emergency Medicine, and junior (MS1, MS2, and
      MS3) medical students (13 total groups). Students completed confidential
      electronic surveys before and after completion of the program. RESULTS: Of 126
      students, 85 completed the Course Evaluation Survey. At program onset, 11.4% of
      1st-year students, 41.7% of 2nd-year students, 50% of 3rd-year students, and 28%
      of the total students could identify a mentor. After completion, 68.6% of 1st
      years, 83.3% of 2nd years, 90% of 3rd years, and 77.6% of the total reported they
      could identify a mentor. Faculty were rated most important members followed by
      the 4th-year student. CONCLUSION: A tiered group mentorship program improved the
      ability of students to identify a mentor. Students identified mentoring
      relationships from individuals at various professional levels.

PMID- 24112202
TI  - The value of bedside rounds: a multicenter qualitative study.
AB  - BACKGROUND: Bedside rounds have decreased on teaching services, raising concern
      about trainees' clinical skills and patient-physician relationships. PURPOSE: We
      sought to identify recognized bedside teachers' perceived value of bedside rounds
      to assist in the promotion of bedside rounds on teaching services. METHODS:
      Authors used a grounded theory, qualitative study design of telephone
      semistructured interviews with bedside teachers (n = 34) from 10 U.S.
      institutions (2010-2011). Main outcomes were characteristics of participants,
      themes pertaining to the perceived value of bedside rounds, and quotations
      highlighting each respective theme. RESULTS: The mean years in academic medicine
      was 13.7, and 51% were associate or full professors. Six main themes emerged: (a)
      skill development for learners (e.g., physical examination, communication, and
      clinical decision-making skills); (b) observation and feedback; (c) role
      modeling; (d) team building among trainees, attending, and patient; (e) improved
      patient care delivery through combined clinical decision-making and team
      consensus; and (f) the culture of medicine as patient-centered care, which was
      embodied in all themes. CONCLUSIONS: Bedside teachers identify potential benefits
      of bedside rounds, many of which align with national calls to change our approach
      to medical education. The practice of bedside rounds enables activities essential
      to high-quality patient care and education.

PMID- 24112203
TI  - Association of learning approaches with academic performance of Sri Lankan first
      year dental students.
AB  - BACKGROUND: Primarily deep approach (DA) and surface approach (SA) to learning
      have been distinguished among students. PURPOSE: We aimed to determine the
      learning approaches and their association with the academic performance of a
      batch of 1st-year Sri Lankan dental students. METHODS: Learning scores of
      students were calculated using the revised two-factor study process (R-SPQ-2F)
      questionnaire and they were correlated with the academic performance of students.
      RESULTS: The 80.65% of students showed a greater DA score than SA score. Mean
      values of students' DA and SA scores were 31.79 +/- 6.1 and 22.74 +/- 5.5,
      respectively. A positive statistically significant correlation (r = .3, p < .05)
      was observed only between DA score and marks of Short Answer Questions in
      anatomy. CONCLUSIONS: This sample of students uses both deep and surface learning
      approaches with more preference to DA than SA. The correlation between learning
      approaches and academic performance was inconsistent.

PMID- 24112204
TI  - An integrated virtual family curriculum to introduce specialty-specific clinical
      skills to rising third-year medical students.
AB  - BACKGROUND: Transitioning from a preclinical to a clinical curriculum can be
      challenging for medical students. As a central component of a new 3-week
      transition course, we designed, implemented, and evaluated an innovative Virtual
      Family Curriculum to introduce rising 3rd-year medical students to the knowledge,
      skills, and cultures of 6 core medical and surgical specialties. DESCRIPTION: The
      authors designed a 6-case, 24-hour, 3-generation Virtual Family Curriculum and a
      6-station summative Objective Structured Clinical Examination (OSCE). Each case
      contains a lecture, video, discussion questions, skills practice, and faculty
      guide. We used both qualitative and quantitative evaluation methods. EVALUATION:
      Ninety-eight students took the inaugural course in 2012. All students passed the
      final OSCE. Students rated the virtual family curriculum a 5.17/6 (6 = highest).
      Comments about the curriculum were uniformly positive. CONCLUSIONS: We created
      and implemented an integrated Virtual Family Curriculum that systematically
      teaches specialty-specific knowledge and skills. This curriculum facilitates
      students' transition to clinical clerkships.

PMID- 24112205
TI  - Domestic global health: a curriculum teaching medical students to evaluate
      refugee asylum seekers and torture survivors.
AB  - BACKGROUND: Seven to 12% of foreign-born patients in the United States has
      experienced torture. We aimed to teach medical students to identify and care for
      asylum seekers/torture survivors. DESCRIPTION: One hundred twenty-five students
      participated in a program consisting of a workshop covering sequelae of torture,
      asylum law, and an approach to patient evaluation; twice-monthly clinical
      sessions; and mentored preparation of medical affidavits. We observed clinical
      encounters; evaluated medical affidavits; and assessed students' knowledge,
      attitudes, and skills pre- and postcurriculum. EVALUATION: Students successfully
      performed physical and psychological evaluations and prepared affidavits
      resulting in 89% asylum application approval. We observed improvement in student
      attitudes toward working with survivors (p < .05), knowledge of sequelae of
      torture (p < .001), and self-efficacy in clinical evaluation (p < .001).
      CONCLUSIONS: Medical students learned necessary skills to provide services for
      survivors, which will also serve them in caring for other vulnerable populations.
      As an advocacy, cultural competency, and domestic global health opportunity, this
      training was feasible and achieved its educational goals.

PMID- 24112206
TI  - How to integrate the electronic health record and patient-centered communication
      into the medical visit: a skills-based approach.
AB  - BACKGROUND: Implementation of the electronic health record (EHR) has changed the
      dynamics of doctor-patient communication. Physicians train to use EHRs from a
      technical standpoint, giving only minimal attention to integrating the human
      dimensions of the doctor-patient relationship into the computer-accompanied
      medical visit. DESCRIPTION: This article reviews the literature and proposes a
      model to help clinicians, residents, and students improve physician-patient
      communication while using the EHR. EVALUATION: We conducted a literature search
      on use of communication skills when interfacing with the EHR. We observed an
      instructional gap and developed a model using evidence-based communication
      skills. CONCLUSION: This model integrates patient-centered interview skills and
      aims to empower physicians to remain patient centered while effectively using
      EHRs. It may also serve as a template for future educational and practice
      interventions for use of the EHR in the examination room.

PMID- 24112207
TI  - Electronic health records: upsides, downsides, and inside-outsides on the way
      toward their use in clinical practice.
AB  - BACKGROUND: The author reviews his personal history learning to use Electronic
      Health Records (EHRs) and examination room computers. He asks key questions that
      pertain to the use of EHRs in practice and discusses the current state of
      knowledge regarding EHRs and doctor-patient communication. SUMMARY: He notes that
      -regardless of the ubiquity of computers in our society and the recognition that
      they are a part of current medical practice--one cannot just plop down a computer
      in the examination room, click "on," and anticipate that communication between
      doctors and patients will flow smoothly. CONCLUSIONS: He recommends the
      accompanying article by Duke, Frankel, and Reis (see p. 358 in this issue) as an
      excellent step-by-step guide for framing how to teach the basics of EHR use in
      clinical practice.

PMID- 24112208
TI  - Professional identity in medical students: pedagogical challenges to medical
      education.
AB  - BACKGROUND: Professional identity, or how a doctor thinks of himself or herself
      as a doctor, is considered to be as critical to medical education as the
      acquisition of skills and knowledge relevant to patient care. SUMMARY: This
      article examines contemporary literature on the development of professional
      identity within medicine. Relevant theories of identity construction are explored
      and their application to medical education and pedagogical approaches to
      enhancing students' professional identity are proposed. The influence of
      communities of practice, role models, and narrative reflection within curricula
      are examined. CONCLUSIONS: Medical education needs to be responsive to changes in
      professional identity being generated from factors within medical student
      experiences and within contemporary society.

PMID- 24112209
TI  - Improving hand hygiene compliance in healthcare settings using behavior change
      theories: reflections.
AB  - BACKGROUND: Although hand hygiene is the most effective method for preventing
      healthcare-associated infections, hand hygiene practice falls short in many
      healthcare facilities. The compliance rate is mostly linked to system design and
      easily accessible hand hygiene products. System change, healthcare worker
      motivation, and complex behavioral considerations seem to play a significant
      role. SUMMARY: This article discusses the application of behavioral theories in
      hand hygiene promotion in a theoretical manner. The program relies on the
      transtheoretical model (TTM) of health behavior change, John Keller's (ARCS)
      Model of Motivational Design, and the theory of planned behavior (TPB). Thus, the
      program links attitudes and behavior to hand hygiene promotion. CONCLUSIONS: The
      TTM of health behavior change helps to tailor interventions to predict and
      motivate individual movement across the pathway to change. A program could be
      based on this theory with multiple intercalations with John Keller's ARCS and the
      TPB. Such a program could be strengthened by linking attitudes and behavior to
      promote hand hygiene. The program could utilize different strategies such as
      organization cultural change that may increase the attention as well as fostering
      the movement in the ARCS stages. In addition, modeling TPB by creating peer
      pressure, ability to overcome obstacles, and increasing knowledge of the role of
      hand hygiene may lead to the desired outcome. The understanding and application
      of behavior change theories may result in an effective program to improve
      awareness and raise intention and thus may increase the potential for success of
      hand hygiene promotion programs.

PMID- 24112210
TI  - A guide to performing pelvic speculum exams: a patient-centered approach to
      reducing iatrogenic effects.
AB  - PURPOSE: Current training in the United States for pelvic speculum examinations
      (PSEs) has a primary focus on the physician-centered goal of visualizing the
      cervix but may not inform practitioners of potential iatrogenic effects. Such
      oversight leaves trainees unprepared and unskilled in preventing and addressing
      adverse outcomes. This article incorporates a literature review into a step-by
      step guide to aid the teaching of PSEs. SUMMARY: Iatrogenic effects of PSEs may
      include mild discomfort, extreme pain, anxiety, psychological (re)traumatization,
      and sexual pain disorders. A literature-based guide is presented to identify
      patients at risk for adverse outcomes, set up the exam room, set up the patient,
      perform the exam, calm distressed patients, and avoid exam-interfering behaviors.
      CONCLUSIONS: Although PSEs can lead to adverse outcomes, awareness of the
      iatrogenic effects allows clinicians to utilize techniques to prevent or reduce
      negative effects. A method of incorporating techniques described in this article
      into teaching is provided.

PMID- 24112214
TI  - Evaluation of different culture methods for the diagnosis of peritonitis in
      patients on continuous ambulatory peritoneal dialysis.
AB  - A total of 170 continuous ambulatory peritoneal dialysis (CAPD) fluids were
      processed by various culture methods, including direct inoculation of the
      centrifuged sediment, inoculation into automated blood culture bottles, water
      lysis, Tween-80 incorporated blood agar, and Triton-X treatment of the specimen.
      Of 170 CAPD fluids, 127 showed the growth of bacteria/fungi. Sixty-three fluids
      showed growth by all methods, the water lysis alone detected 24 additional
      positive cultures, while Tween-80 blood agar and Triton-X yielded 30 additional
      positive cultures. A combination of water lysis, Tween-80 blood agar and Triton-X
      treatment of the CAPD fluid is recommended for diagnosis of CAPD peritonitis in
      resource-limited settings. 

PMID- 24112216
TI  - How genetic studies have advanced our understanding of age-related macular
      degeneration and their impact on patient care: a review.
AB  - The last 10 years have seen an unprecedented explosion in our knowledge regarding
      the genomic basis of age-related macular degeneration. This has come about
      through major advances in computing power, microfabrication of large numbers of
      molecular markers on chips and improved statistical algorithms for analysis. In
      tandem, it has become clear that age-related macular degeneration appears to be a
      multifactorial disease with influences from genetic and structural variants, as
      well as epigenetic involvement. The combination of these factors with known
      environmental determinants indicates the highly complex nature of this disease,
      but at the same time also offers insights into risk prediction and disease
      stratification through genotype profiling. 

PMID- 24112215
TI  - Understanding the medicines information-seeking behaviour and information needs
      of South African long-term patients with limited literacy skills.
AB  - BACKGROUND: Although much health information-seeking behaviour (HISB) research
      has been reported in patients with good literacy skills, little is known about
      HISB in patients with limited literacy skills served by under-resourced health
      care systems. OBJECTIVE: To investigate medicine information-seeking behaviour
      and information needs in patients with limited literacy. METHODS: Using a
      question guide, four focus group discussions (FGDs) were conducted to explore
      themes related to information needs, information-seeking practices and awareness
      of and ability to utilize information sources. Twenty-two isiXhosa-speaking long
      term patients with limited formal education were recruited from a primary health
      care clinic in South Africa. Discussions were audio-recorded and transcribed
      verbatim. NVivo((r)) was used for initial coding of transcripts. Codes were
      analysed, and potential themes and subthemes in the entire data set were
      identified and refined. FINDINGS: The results of this study reflect a passive,
      disempowered patient. Poor awareness of information sources, lack of health
      related knowledge and stigma contributed to a lack of information-seeking
      practice, thus potentially adversely influencing patient-provider interactions.
      Patients neither asked questions nor were encouraged to ask questions. All
      expressed an unmet need for information and a desire for receiving the
      illustrated written medicines-related information displayed in the FGDs. The main
      sources of information were health-care professionals, followed by family and
      friends. CONCLUSION: The significant level of patient disempowerment and
      passivity reported amongst patients underpinned their inability to actively seek
      information. Neither sources of information nor types of appropriate medicines
      information could be identified. Unmet information needs and a desire for
      information were reported.

PMID- 24112217
TI  - Improving quality-of-life outcomes for patients with cancer through mediating
      effects of depressive symptoms and functional status: a three-path mediation
      model.
AB  - AIMS AND OBJECTIVES: To test a hypothetical three-path mediation model evaluating
      the effects of functional status and depressive symptoms on the relationship
      between fatigue and quality of life in patients with cancer on the basis of the
      Theory of Unpleasant Symptoms. BACKGROUND: Patients with cancer often experience
      two or more concurrent, interrelated, mutually influential symptoms. Multiple
      unpleasant symptoms that have been proposed as mediating variables affecting
      quality of life in a model proposed in recent cancer studies are scanty. DESIGN:
      This study was a cross-sectional, descriptive, correlational design. METHODS:
      Three hundred and twenty-six patients with cancer from oncology clinics were
      recruited in Taiwan between 2010-2011. Mediation models were tested and confirmed
      by applying structural modelling using Analysis of Moment Structures and the
      joint significance test. RESULTS: Fatigue affects patient quality of life
      directly or indirectly through functional status and depressive symptoms. These
      two mediating variables exhibited direct effects on quality of life. A path
      analysis approach revealed that 47.28 and 67.70% of the total effects of
      functional status and depressive symptoms, respectively, on the quality-of-life
      mediation models are attributable to 29.6 and 44.7% of the total effects between
      fatigue and quality of life, which mediated through two mediators, respectively.
      CONCLUSION: Quality of life may be enhanced by simultaneously improving
      physiological and psychological factors. RELEVANCE TO CLINICAL PRACTICE: An
      understanding of mediating effects is valuable in nursing care of patients with
      cancer, particularly in the early phase of treatment or in newly diagnosed stages
      I-III or recently treated patients with cancer in different disease stages.

PMID- 24112218
TI  - Tobacco smoking, associated risk behaviours, and experience with quitting: a
      qualitative study with homeless smokers addicted to drugs and alcohol.
AB  - BACKGROUND: The prevalence of tobacco smoking among homeless people can reach
      more than 90%, with related morbidity and mortality being high. However, research
      in this area is scarce. This study aims to explore smoking and quitting related
      behaviours, experiences and knowledge in homeless smokers in the context of other
      substance abuse. METHODS: Face-to-face interviews were conducted with homeless
      smokers accessing a harm reduction service in Nottingham, UK. Data on smoking
      history, nicotine dependence, motivation and confidence to quit were collected
      using structured instruments; a semi-structured interview guide was used to
      elicit responses to predefined subject areas, and to encourage the emergence of
      unprecedented themes. Data were analysed using framework analysis and descriptive
      statistics. RESULTS: Participants were generally highly dependent smokers who did
      not display good knowledge/awareness of smoking related harms and reported to
      engage in high risk smoking behaviours. The majority reported notable motivation
      and confidence to quit in the future, despite or indeed for the benefit of
      addressing other dependencies. Of the many who had tried to quit in the past, all
      had done so on their own initiative, and several described a lack of support or
      active discouragement by practitioners to address smoking. CONCLUSION: High
      levels of tobacco dependence and engagement in unique smoking related risk
      behaviours and social interplays appear to add to the vulnerability of homeless
      smokers. Given reported motivation, confidence, previous attempts and lack of
      support to quit, opportunities to address smoking in one of the most
      disadvantaged groups are currently missed.

PMID- 24112219
TI  - Medical interventions for children with trisomy 13 and trisomy 18: what is the
      value of a short disabled life?
AB  - Children with trisomy 13 and trisomy 18 (T13 or T18) have low survival rates, and
      survivors have significant disabilities. Life saving interventions (LSIs) are
      generally not recommended by many healthcare providers (HCPs). After a diagnosis
      of T13 or T18, many parents chose termination of pregnancy or comfort care at
      birth, but others consider treatment to prolong the lives of their children.
      While LSIs may be effective at prolonging the life of some children, the quality
      of life of survivors and the possible burden on the family may be considered
      negatively by HCP, which may lead to conflicts with families. Resource allocation
      considerations are often invoked to withhold LSI for T13 or T18 even though they
      are seldom mentioned for older patients with comparable outcomes. CONCLUSION: We
      should strive to improve communication with parents by 1. Investigating these
      conditions further to be able to better inform parents and 2. Providing balanced
      information for families and personalised care for each child.

PMID- 24112220
TI  - Evidence of clinically significant extravascular stores of factor IX.

PMID- 24112221
TI  - Appliance-induced osteopenia of dentoalveolar bone in the rat: effect of reduced
      bone strains on serum bone markers and the multifunctional hormone leptin.
AB  - To understand, in greater detail, the molecular mechanisms regulating the complex
      relationship between mechanical strain and alveolar bone metabolism during
      orthodontic treatment, passive cross-arch palatal springs were bonded to the
      maxillary molars of 6-wk-old rats, which were killed after 4 and 8 d. Outcome
      measures included serum assays for markers of bone formation and resorption and
      for the multifunctional hormone leptin, and histomorphometry of the inter
      radicular bone. The concentration of the bone-formation marker alkaline
      phosphatase (ALP) was significantly reduced at both time points in the appliance
      group, accompanied by a 50% reduction in inter-radicular bone volume; however,
      osteocalcin (bone Gla protein) levels remained unaffected. Bone collagen
      deoxypyridinoline (DPD) crosslinks increased 2.3-fold at 4 d only, indicating a
      transient increase in bone resorption; in contrast, the level of the osteoclast
      specific marker, tartrate-resistant acid phosphatase 5b (TRACP 5b), was
      unchanged. Leptin levels closely paralleled ALP reductions at both time points,
      suggesting an important role in the mechanostat negative-feedback loop required
      to normalize bone mass. These data suggest that an orthodontic appliance, in
      addition to remodeling the periodontal ligament (PDL)-bone interface, may exert
      unexpected side-effects on the tooth-supporting alveolar bone, and highlights the
      importance of recognizing that bone strains can have negative, as well as
      positive, effects on bone mass.

PMID- 24112222
TI  - Optimism and proactive coping in relation to burnout among nurses.
AB  - AIM: The study investigated the three symptoms of burnout among hospital nurses
      and examined the buffering effects of optimism and proactive coping in relation
      to burnout. BACKGROUND: Nursing is a profession that can easily lead to burnout.
      Burnout has been one of the most investigated work outcomes in current research.
      Previous research has largely ignored the positive influence of individuals on
      job outcomes and has not tested a constructive framework that might facilitate
      interventions to prevent burnout. METHOD: A cross-sectional survey of 314 staff
      nurses in general hospitals in Taiwan. Participants completed a set of
      questionnaires with demographic information. FINDING: The findings suggested that
      higher levels of proactive coping behaviours and optimism were associated with
      lower levels of burnout. Optimism was found to have the strongest relationship
      with the decreased personal accomplishment of burnout. CONCLUSION: The findings
      of this study confirmed the importance of optimism and proactive coping in
      prevention of symptoms of burnout. IMPLICATIONS FOR NURSING MANAGEMENT: The
      results of this study provided important recommendations regarding stress
      management interventions for health-care managers, nurses, psychologists and
      human resource staff in the reduction of burnout to promote mental health in an
      organisation.

PMID- 24112223
TI  - The effectiveness of telemedicine for weight management in the MOVE! Program.
AB  - PURPOSE: To examine the effectiveness of videoconferencing technology for
      delivering comprehensive weight management treatment. METHODS: This retrospective
      cohort study was conducted by extraction of data from medical records for the
      years 2008-2010. The treatment included a series of 12 weekly MOVE!(r) classes
      delivered using videoconferencing. Data were extracted from the time of baseline
      weight to 1 year after baseline weight for the MOVE! participants (n = 60) and
      from a concurrent control group (n = 60) that did not participate in MOVE!
      treatment. FINDINGS: Results indicated that the MOVE! group lost weight while the
      control group gained weight, resulting in a mean difference between the groups of
      -5.5 +/- 2.7 kg (95% CI = -8.0 to -3.0; P < .0001). CONCLUSIONS: These results
      indicate that videoconferencing is an effective method to provide the MOVE!
      Weight Management Program to veterans. Weight loss was maintained for one year
      after baseline in the MOVE! group. This is very promising as weight re-gain is a
      common issue and these results support using videoconferencing for a long-term
      weight management treatment option.

PMID- 24112224
TI  - Re-examining dry eye disease.

PMID- 24112225
TI  - Fluorescein: its use in investigation of lacrimal characteristics.

PMID- 24112226
TI  - Tear fluid biomarker profiling: a review of multiplex bead analysis.
AB  - Developments in the field of tear film protein profiling are reviewed, including
      the advantages and disadvantages of the multiplex bead array technique and its
      potential for identifying biomarkers of ocular surface disease. Commercial kits,
      which specifically employ 96-well plates with polystyrene microspheres and
      magnetic beads, and sensitivity variations between them are discussed.
      Modifications to protocols of these kits (which are designed primarily for larger
      sample volumes, such as blood and cell culture supernatants) may be necessary for
      tear fluid samples. Multiplex bead array is compared to the "gold standard,"
      ELISA. The challenges of diagnosing and monitoring dry eye disease, due to the
      conflicting and variable signs and symptoms presented, are illustrated by the
      authors' own study results. The development of a biomarker profile for the
      disease would be a useful approach to the ongoing problems of diagnosis. The
      multiplex bead array technique has important potential applications in this
      regard. 

PMID- 24112228
TI  - Role of hyperosmolarity in the pathogenesis and management of dry eye disease:
      proceedings of the OCEAN group meeting.
AB  - Dry eye disease (DED), a multifactorial disease of the tears and ocular surface,
      is common and has a significant impact on quality of life. Reduced aqueous tear
      flow and/or increased evaporation of the aqueous tear phase leads to tear
      hyperosmolarity, a key step in the vicious circle of DED pathology. Tear
      hyperosmolarity gives rise to morphological changes such as apoptosis of cells of
      the conjunctiva and cornea, and triggers inflammatory cascades that contribute to
      further cell death, including loss of mucin-producing goblet cells. This
      exacerbates tear film instability and drives the cycle of events that perpetuate
      the condition. Traditional approaches to counteracting tear hyperosmolarity in
      DED include use of hypotonic tear substitutes, which have relatively short
      persistence in the eye. More recent attempts to counteract tear hyperosmolarity
      in DED have included osmoprotectants, small organic molecules that are used in
      many cell types throughout the natural world to restore cell volume and stabilize
      protein function, allowing adaptation to hyperosmolarity. There is now an
      expanding pool of clinical data on the efficacy of DED therapies that include
      osmoprotectants such as erythritol, taurine, trehalose and L-carnitine.
      Osmoprotectants in DED may directly protect cells against hyperosmolarity and
      thereby promote exit from the vicious circle of DED physiopathology. 

PMID- 24112227
TI  - Four characteristics and a model of an effective tear film lipid layer (TFLL).
AB  - It is proposed that a normal, effective tear film lipid layer (TFLL) should have
      the following four characteristics: 1) high evaporation resistance to prevent
      water loss and consequent hyperosmolarity; 2) respreadability, so it will return
      to its original state after the compression-expansion cycle of the blink; 3)
      fluidity sufficient to avoid blocking secretion from meibomian glands; 4) gel
      like and incompressible structure that can resist forces that may tend to disrupt
      it. These characteristics tend to be incompatible; for example, lipids that form
      good evaporation barriers tend to be disrupted by compression-expansion cycles.
      It is noted that clues about the function and organization of the TFLL can be
      obtained by comparison with other biological lipid layers, such as lung
      surfactant and the lipid evaporation barrier of the skin. In an attempt to
      satisfy the conflicting characteristics, a "multilamellar sandwich model" of the
      TFLL is proposed, having features in common with the skin evaporation barrier. 

PMID- 24112229
TI  - Current medical treatment of ocular mucous membrane pemphigoid.
AB  - Ocular mucous membrane pemphigoid (MMP), as a potentially blinding disease, is an
      indication for systemic immunosuppressive treatment. Immunosuppressive agents are
      chosen with a "stepladder" approach, beginning with drugs having the fewest side
      effects. Dapsone, sulfapyridine/sulfasalazine and azathioprine are less
      successful in controlling inflammation than mycophenolate mofetil (MMF) and
      methotrexate (MTX). Moreover, compared to other immunosuppressive agents, MMF,
      followed by MTX, has the lowest rate of discontinuation due to side effects.
      Cyclophosphamide is the most potent immunosuppressive agent used for ocular MMP,
      but it should be used with caution because of life-threatening adverse effects.
      Intravenous immunoglobulin therapy (IVIg) should be considered for patients who
      are resistant to conventional immunosuppressive therapy, have significant adverse
      effects or contraindications to conventional therapy, or have uncontrolled
      rapidly progressive disease. If IVIg monotherapy is not successful after a period
      of >= 1 year, therapy with biological agents, such as rituximab or anti-TNF-alpha
      drugs, is suggested.

PMID- 24112230
TI  - Statistical approaches to assessing single and multiple outcome measures in dry
      eye therapy and diagnosis.
AB  - Dry eye is a multifactorial disease which would require a broad spectrum of test
      measures in the monitoring of its treatment and diagnosis. However, studies have
      typically reported improvements in individual measures with treatment.
      Alternative approaches involve multiple, combined outcomes being assessed by
      different statistical analyses. In order to assess the effect of various
      statistical approaches to the use of single and combined test measures in dry
      eye, this review reanalyzed measures from two previous studies (osmolarity,
      evaporation, tear turnover rate, and lipid film quality). These analyses assessed
      the measures as single variables within groups, pre- and post-intervention with a
      lubricant supplement, by creating combinations of these variables and by
      validating these combinations with the combined sample of data from all groups of
      dry eye subjects. The effectiveness of single measures and combinations in
      diagnosis of dry eye was also considered. 

PMID- 24112231
TI  - Fill size for ophthalmic products.

PMID- 24112232
TI  - Smoldering multiple myeloma: present position and potential promises.
AB  - Since smoldering multiple myeloma (SMM) was first described over three decades
      ago based on a case series of six patients, its definition and our understanding
      of the entity have evolved considerably. The risk of progression to symptomatic
      myeloma (MM) varies greatly among individuals diagnosed with myeloma precursor
      disease. Epidemiologic, molecular, flow cytometric and radiological techniques
      have demonstrated that this transformation to MM from precursor states is not
      sudden but rather a continuous overlapping series of events with evidence of end
      organ damage that could manifest in the earliest stages of disease. Contemporary
      antimyeloma therapies can yield rapid, deep, and durable responses with
      manageable toxicities, and molecular-cell-based measures are now available to
      rule out minimal residual disease. With this information, clinical studies with
      correlative measures can now be developed to test the fundamental hypothesis that
      intervention in early myeloma may provide a measurable clinical benefit to
      patients by either delaying progression or eradicating plasma cell clones. 

PMID- 24112233
TI  - Microsurgical management of giant malignant peripheral nerve sheath tumor of the
      scalp: two case reports and a literature review.
AB  - Malignant peripheral nerve sheath tumors of the scalp are rare lesions of the
      nervous system. Only 14 cases have been reported to date. The field of
      neurosurgery has struggled with diagnosing and treating these tumors. In this
      report, we present two cases of giant malignant peripheral nerve sheath tumors of
      the scalp and retrospectively analyze the clinical features, imaging findings,
      pathological features, and prognoses of these two patients. Each underwent
      microsurgery and radiotherapy. In addition, based on a literature review, we
      discuss the diagnostic and therapeutic strategies used to treat these unusual
      lesions. 

PMID- 24112234
TI  - Differentiation of nonhuman primate embryonic stem cells into hepatocyte-like
      cells.
AB  - OBJECTIVE: To investigate whether cells derived from rhesus monkey embryonic stem
      cells (ESC) had hepatocyte characteristics after the differentiation. METHODS:
      Rhesus monkey ESC were induced towards hepatocyte-like cells via a four-step
      differentiation process: the formation of embryoid bodies (EB), EB in activin A
      and insulin-transferrin-selenium medium for 4 days, in fibroblast growth factor
      (FGF)-4 and bone morphogenetic protein-2 (BMP2) medium for 8 days, in hepatocyte
      culture medium containing hepatocyte growth factor for 3 days and then with
      oncostatin M and dexamethasone for another 5 days. Expression of albumin (ALB),
      glucose-6-phosphatase, alpha-fetoprotein (AFP) and alpha-1 antitrypsin (alpha1
      AT) at the mRNA level in differentiated cells were detected by reverse
      transcription-polymerase chain reaction. The expression of hepatocyte markers
      AFP, ALB, hepatocyte nuclear factor 4 (HNF4), cytokeratin 8 (CK8), CK19 and cell
      proliferation marker, Ki67, in the differentiated cells were determined by
      immunocytochemistry. The ultrastructure of the differentiated cells was examined
      by electron microscopy. Indocyanine green (ICG) uptake was also explored.
      RESULTS: After induction, some differentiated cells were binucleate, which is
      typical of hepatocytes. Hepatocyte-specific genes ALB, glucose-6-phosphatase, AFP
      and alpha1-AT were expressed in the differentiated cells. The differentiated
      cells expressed hepatocyte markers AFP, ALB, HNF4, CK8 and CK19 at the protein
      level. The cells also expressed cell proliferation marker Ki67. Under electron
      microscopy, the ultrastructures of hepatocyte-like cells, such as mitochondrion
      and catalase-containing peroxisomes, were observed in the differentiated cells.
      ICG uptake test was positive in differentiated cells. CONCLUSIONS: With cytokine
      induction, rhesus monkey ESC differentiated into cells displaying morphological
      features, gene expression patterns and metabolic activities characteristic of
      hepatocytes.

PMID- 24112235
TI  - Decrease in bispectral index prior to cardiovascular collapse during Caesarean
      sections.
AB  - We report a case of significant reduction in bispectral index (BIS) associated
      with suspected amniotic fluid embolism (AFE) that occurred prior to change in
      haemodynamic variables. The patient was a 29-year-old nulliparous, who was
      admitted for Caesarean section under general anaesthesia in the 33rd week of
      pregnancy. After the baby was born, the BIS value suddenly decreased to 0, with
      suppression ratio of 100. One minute later, saturation decreased abruptly to 85%,
      end-tidal carbon dioxide (EtCO2) decreased to 5 mmHg, peak inspiratory pressure
      increased to 35 cm H2O, and non-invasive blood pressure (BP) failed to obtain a
      reading. After administration of vasoactive drugs, the systolic BP was maintained
      at 100 mmHg or higher, the BIS value rose to 10-20, and the EtCO2 increased to 24
      33 mmHg. In this case, the BIS monitoring may provide an earlier warning of
      impending cardiovascular collapse in the case of AFE. 

PMID- 24112236
TI  - Early liver retransplantation in adults.
AB  - Up to 23% of liver allografts fail post-transplant. Retransplantation is only the
      recourse but remains controversial due to inferior outcomes. The objective of our
      study was to identify high-risk periods for retransplantation and then compare
      survival outcomes and risk factors. We performed an analysis of United Network
      for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through
      2011. We analyzed the records of 49,288 recipients; of those, 2714 (5.5%)
      recipients were retransplanted. Our analysis included multivariate regression
      with the outcome of retransplantation. The highest retransplantation rates were
      within the first week (19% of all retransplantation, day 0-7), month (20%, day 8
      30), and year (33%, day 31-365). Only retransplantation within the first year
      (day 0-365) had below standard outcomes. The most significant risk factors were
      as follows: within the first week, cold ischemia time >16 h [odds ratio (OR)
      3.6]; within the first month, use of split allografts (OR 2.9); and within the
      first year, use of a liver donated after cardiac death (OR 4.9). Each of the
      three high-risk periods within the first year had distinct causes of graft
      failure, risk factors for retransplantation, and survival rates after
      retransplantation.

PMID- 24112238
TI  - Nectin and junctional adhesion molecule are critical cell adhesion molecules for
      the apico-basal alignment of adherens and tight junctions in epithelial cells.
AB  - Tight junctions (TJs) and adherens junctions (AJs) form an apical junctional
      complex at the apical side of the lateral membranes of epithelial cells, in which
      TJs are aligned at the apical side of AJs. Many cell adhesion molecules (CAMs)
      and cell polarity molecules (CPMs) cooperatively regulate the formation of the
      apical junctional complex, but the mechanism for the alignment of TJs at the
      apical side of AJs is not fully understood. We developed a cellular system with
      which epithelial-like TJs and AJs were reconstituted in fibroblasts and analyzed
      the cooperative roles of CAMs and CPMs. We exogenously expressed various
      combinations of CAMs and CPMs in fibroblasts that express negligible amounts of
      these molecules endogenously. In these cells, the nectin-based cell-cell adhesion
      was formed at the apical side of the junctional adhesion molecule (JAM)-based
      cell-cell adhesion, and cadherin and claudin were recruited to the nectin-3- and
      JAM-based cell-cell adhesion sites to form AJ-like and TJ-like domains,
      respectively. This inversed alignment of the AJ-like and TJ-like domains was
      reversed by complementary expression of CPMs Par-3, atypical protein kinase C,
      Par-6, Crb3, Pals1 and Patj. We describe the cooperative roles of these CAMs and
      CPMs in the apico-basal alignment of TJs and AJs in epithelial cells. 

PMID- 24112237
TI  - The 7-valent pneumococcal conjugate vaccine elicits cross-functional
      opsonophagocytic killing responses to Streptococcus pneumoniae serotype 6D in
      children.
AB  - BACKGROUND: We investigated the immune response to serogroup 6 with the
      opsonophagocytic killing assay (OPKA) in children aged 12-23 months of age after
      immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) containing
      serotype 6B. METHODS: Blood samples were obtained from 59 children who had blood
      sampling for medical examination. Immunization status against PCV7 was confirmed
      by immunization records and samples were categorized according to immunization
      status into a booster, primary, or control group. The OPKA was performed for
      serotypes 6A, 6B, 6C, and 6D. RESULTS: Subjects with no previous PCV7
      immunization history showed opsonic activity for serogroup 6 in 5-30% (according
      to serotype). In subjects vaccinated with a 3-dose primary series, 81% showed
      opsonic activity for serotypes 6B and 6D, and 29% showed opsonic activity for
      serotypes 6A and 6C. Among subjects vaccinated with a booster dose, all subjects
      had opsonic activity against serotype 6B. Subjects in the booster group with
      opsonic activity against serotypes 6A, 6C, and 6D were 100%, 78%, and 89%,
      respectively. CONCLUSIONS: In subjects aged 12-23 months, an immune response is
      elicited after a primary series of immunizations with PCV7 for serotypes 6B and
      6D, and a booster dose enhances a cross reactive immune response against
      serotypes 6A, 6C and 6D.

PMID- 24112240
TI  - Integrating DNA barcodes and morphology for species delimitation in the
      Corynoneura group (Diptera: Chironomidae: Orthocladiinae).
AB  - In this study, we use DNA barcodes for species delimitation to solve taxonomic
      conflicts in 86 specimens of 14 species belonging to the Corynoneura group
      (Diptera: Chironomidae: Orthocladiinae), from the Atlantic Forest, Brazil.
      Molecular analysis of cytochrome c-oxidase subunit I (COI) gene sequences
      supported 14 cohesive species groups, of which two similar groups were
      subsequently associated with morphological variation at the pupal stage. Eleven
      species previously described based on morphological criteria were linked to DNA
      markers. Furthermore, there is the possibility that there may be cryptic species
      within the Corynoneura group, since one group of species presented internal
      grouping, although no morphological divergence was observed. Our results support
      DNA-barcoding as an excellent tool for species delimitation in groups where
      taxonomy by means of morphology is difficult or even impossible. 

PMID- 24112239
TI  - The lifetime prevalence of anabolic-androgenic steroid use and dependence in
      Americans: current best estimates.
AB  - BACKGROUND AND OBJECTIVES: Although various surveys have tracked the prevalence
      of anabolic-androgenic steroid (AAS) use in American teenagers and young adults,
      no recent surveys have assessed the lifetime prevalence of AAS use in Americans
      overall. We therefore analyzed serial youth-survey data to derive estimates of
      the lifetime prevalence of AAS use in the current American general population.
      METHODS: We first determined the distribution of age of onset of AAS use, based
      on pooled data from nine studies. Using this distribution, we then developed
      equations to project the eventual lifetime prevalence of AAS use among young
      survey respondents, once they aged and completed the period of risk for
      initiating AAS. We similarly calculated the denominator of lifetimes of risk for
      AAS use in the total American population. We next applied these equations to four
      independent national youth datasets to derive current American general-population
      estimates for lifetime AAS use. Finally, using data from 10 pooled studies, we
      estimated the lifetime prevalence of AAS dependence among AAS users. RESULTS: Age
      of-onset studies consistently showed that AAS use begins later than most drugs,
      with only 22% of users (95% confidence interval: 19-25%) starting before age 20.
      Applying the age-of-onset findings to national youth datasets, we estimated that
      among Americans currently age 13-50 years, 2.9-4.0 million have used AAS. Within
      this group, roughly 1 million may have experienced AAS dependence. CONCLUSIONS
      AND SCIENTIFIC SIGNIFICANCE: Although subject to various limitations, our
      estimation techniques suggest a surprisinigly high prevalence of AAS use and
      dependence among Americans.

PMID- 24112241
TI  - Diversity, heterogeneity and orientation-dependent variation of spike count
      correlation in the cat visual cortex.
AB  - Cortical neurons are known to be noisy encoders of information, showing large
      response variabilities with repeated presentations of identical stimuli. These
      spike count variabilities are correlated over the cell population and their
      neuronal mechanism and functional significance have not been well understood.
      Recently there has been much debate over the magnitude of the population mean of
      the correlation, ranging from 0.1 to 0.2 down to nearly zero. We performed multi
      neuron recordings on the cat visual cortex and found that the population mean did
      not necessarily represent the nature of correlated variabilities because the
      spike count correlation showed significant diversity and heterogeneity. Although
      the population mean was relatively small (0.06), the correlations of individual
      unit pairs were distributed over a broad range, extending to both positive and
      negative values. In most of the recording sessions of local cell populations
      (83%), significantly positive correlations coexisted with significantly negative
      ones in different unit pairs. Furthermore, nearly 20% of the unit pairs showed
      significant variation in the spike count correlation for different stimulus
      orientations. Correlation analysis between the spike count correlation and the
      firing activity of the unit pair suggested that the orientation tuning properties
      of the two quantities were unlikely to have originated from a common neuronal
      mechanism. Diversity, heterogeneity and context-dependent variation suggests that
      the correlated spike count variabilities originate not from fixed anatomical
      connections but rather from the dynamic interaction of neuronal networks. 

PMID- 24112242
TI  - Size at birth and abdominal adiposity in adults: a systematic review and meta
      analysis.
AB  - We performed a systematic literature review on the associations between birth
      size and abdominal adiposity in adults, while also investigating the role of the
      adjustment for adult body mass index (BMI). MEDLINE, Scopus, Web of Science,
      LILACS and SciELO databases were searched for articles published up to February
      2013. Only prospective studies were included. After screening 2,570 titles, we
      selected 31 publications for the narrative synthesis, of which 13 were considered
      to be of high methodological quality. Six main indicators of birth size were
      identified, and birth weight (BW) was the most extensively studied. Most studies
      relied on anthropometric measurements as proxies for abdominal fatness or as
      indicators of body fat distribution. Few studies assessed abdominal adiposity
      through imaging methods, generally with small sample sizes. Eleven articles could
      be included in the meta-analyses. BW was found to be positively associated with
      waist circumference in adulthood, but the association disappeared after
      adjustment for adult BMI. In contrast, there was no association between BW and
      waist-to-hip ratio, whereas a strong negative association became evident after
      controlling for adult BMI. In conclusion, BW seems to be associated with larger
      adult size in general, including both waist and hip circumferences. The marked
      change in coefficients after adjustment for adult BMI suggests that post-natal
      growth strongly affects relative central adiposity, whereas BW per se does not
      play a role. Given the potential impact of post-natal growth, further research is
      needed to identify different growth trajectories that lead to abdominal
      adiposity, as well as studies on interactions of foetal and post-natal growth
      patterns. 

PMID- 24112243
TI  - In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus
      complex.
AB  - The in vitro activity of cefoxitin and imipenem was compared for 43 strains of
      the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis
      patients. The MICs of imipenem were lower than those of cefoxitin, although the
      number of imipenem-resistant strains was higher according to the CLSI
      breakpoints. Strain comparisons indicated that the MICs of cefoxitin were
      significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs
      of both beta-lactams were higher for the rough morphotype than for the smooth
      morphotype. The clinical impact of the in vitro difference between the activity
      of imipenem and that of cefoxitin remains to be determined.

PMID- 24112244
TI  - Changes in use of time, activity patterns, and health and wellbeing across
      retirement: design and methods of the life after work study.
AB  - BACKGROUND: Retirement is a major life transition during which people restructure
      everyday activities; however little is known about this. The primary aim of the
      Life After Work study is to comprehensively measure changes in time use and
      patterns of physical activity and sedentary behaviour, and its associations with
      health and wellbeing, across the retirement transition. METHODS/DESIGN: A target
      sample of 120 participants aged 50 years and over will be recruited in two
      Australian state capital cities, Adelaide and Brisbane. Participants will
      undertake a battery of assessments approximately 3 months prior to retirement,
      and 3, 6 and 12 months post-retirement. Measures will include self-reported use
      of time (using the Multimedia Activity Recall for Children and Adults),
      objectively assessed physical activity and sedentary behaviour (using Actigraph
      GT3X+ accelerometers), self-reported health and well-being (using a battery of
      questionnaires including the Short-Form Health Survey (SF-36), Australian Unity
      Personal Well-being Index (AUPWI), Depression Anxiety Stress Scales 21 (DASS21),
      Short Warwick-Edinburgh Mental Well-being Scale, UCLA Loneliness Scale, Rosenberg
      Self-Esteem Scale), retirement circumstances and socio-demographic
      characteristics, objectively assessed anthropometric measures (height, weight and
      waist circumference), and resting blood pressure. Multivariate mixed models will
      be used to examine changes in use of time, health and well-being across
      retirement. DISCUSSION: The results will provide important new information that
      will inform the development of lifestyle and policy interventions to address and
      improve health and well-being in retirement.

PMID- 24112245
TI  - Ghrelin and motilin receptor agonists: a long and winding misconception.

PMID- 24112246
TI  - Genetic study of diabetic retinopathy: recruitment methodology and analysis of
      baseline characteristics.
AB  - BACKGROUND: Diabetic retinopathy (DR) is a blinding disease of increasing
      prevalence that is caused by a complex interplay of genetic and environmental
      factors. Here we describe the patient recruitment methodology, case and control
      definitions, and clinical characteristics of a study sample to be used for genome
      wide association analysis to detect genetic risk variants of DR. METHODS: One
      thousand six hundred sixty-nine participants with either type 1 (T1) or type 2
      (T2) diabetes mellitus (DM) aged 18 to 95 years were recruited in Australian
      hospital clinics. Individuals with T2DM had disease duration of at least 5 years
      and were taking oral hypoglycaemic medication, and/or insulin therapy.
      Participants underwent ophthalmic examination. Medical history and biochemistry
      results were collected. Venous blood was obtained for genetic analysis. RESULTS:
      Six hundred eighty-three diabetic cases (178 T1DM and 505 T2DM participants) with
      sight-threatening DR, defined as severe non-proliferative DR, proliferative DR or
      diabetic macular oedema were included in this analysis. Eight hundred twelve
      individuals with DM but no DR or minimal non-proliferative DR were recruited as
      controls (191 with T1DM and 621 with T2DM). The presence of sight-threatening DR
      was significantly correlated with DM duration, hypertension, nephropathy,
      neuropathy, HbA1C and body mass index. Diabetic macular oedema was associated
      with T2DM (P < 0.001), whereas proliferative DR was associated with T1DM (P <
      0.001). CONCLUSIONS: Adoption of a case-control study design involving extremes
      of the DR phenotype makes this a suitable cohort, for a well-powered genome-wide
      association study to detect genetic risk variants for DR.

PMID- 24112247
TI  - Immune response after systematic lymph node dissection in lung cancer surgery:
      changes of interleukin-6 level in serum, pleural lavage fluid, and lung
      supernatant in a dog model.
AB  - BACKGROUND: Systematic nodal dissection (SND) is regarded as a core component of
      lung cancer surgery. However, there has been a concern on the increased morbidity
      associated with SND. This study was performed to investigate whether or not SND
      induces significant immune response. METHODS: Sixteen dogs were divided into two
      groups; group 1 (n = 8) underwent thoracotomy only, and group 2 (n = 8) underwent
      SND after thoracotomy. We compared interleukin-6 (IL-6) levels in serum, pleural
      lavage fluid and lung supernatant at the time of thoracotomy (T0) and at 2 h(T1)
      after thoracotomy (group 1) or SND (group 2). Severity of inflammation and IL-6
      expression in lung tissue were evaluated in a semi-quantitative manner. RESULTS:
      The operative results were comparable. IL-6 was not detected in serum in either
      group. IL-6 in pleural lavage fluid marginally increased from 4.75 +/- 3.74 pg/mL
      at T0 to 19.75 +/- 8.67 pg/mL at T1 in group 1 (P = 0.112), and from 7.75 +/-
      5.35 pg/mL to 17.72 +/- 8.58 pg/mL in group 2 (P = 0.068). IL-6 in lung
      supernatant increased from 0.36 +/- 0.14 pg/mL/mg to 1.15 +/- 0.17 pg/mL/mg in
      group 1 (P = 0.003), and from 0.25 +/- 0.08 pg/mL/mg to 0.82 +/- 0.17 pg/mL/mg in
      group 2 (P = 0.001). However, the degree of increase in IL-6 in pleural lavage
      fluid and lung supernatant were not different between two groups (P = 0.421 and P
      = 0.448). There was no difference in severity of inflammation and IL-6 expression
      between groups. CONCLUSIONS: SND did not increase IL-6 in pleural lavage fluid
      and lung supernatant. This result suggests that SND could be routinely performed
      in lung cancer surgery without increasing the significant inflammatory response.

PMID- 24112248
TI  - Evaluation of nurse staffing levels and outcomes under the government-
      recommended staffing levels in Korea.
AB  - AIM: This study aimed to evaluate registered nurse staffing levels and outcomes
      enforced by the current Korean nursing regulations. BACKGROUND: Registered nurse
      staffing levels are closely related to patient and nurse outcomes. Thus, the
      government's policy regarding nursing staffing has a practical impact, and better
      policies could lead to more appropriate nurse staffing. The actual evaluation of
      the government-recommended staffing levels in Korea is paramount for the
      establishment of a realistic and effective system that promotes quality care and
      patient safety. METHOD: The participating hospital operated under the government
      recommended staffing levels (Grade 2 of the Graded Fee of Nursing Management
      Inpatient System). For unit-level evaluations, one surgical unit was chosen and
      its staffing level was changed by assigning one additional registered nurse for 6
      months. Length of hospitalisation, incidents of death, overtime hours and nursing
      job performance were measured prior to and after the addition of the extra staff.
      RESULT: After 6 months, the length of patient hospitalisation and registered
      nurse overtime hours reduced and nurse job performance scores in the unit
      analysed improved. CONCLUSIONS AND IMPLICATIONS FOR NURSING MANAGEMENT: The
      results demonstrated that increasing the number of registered nurses beyond the
      current government-recommended staffing level improves patient and nurse
      outcomes. This indicates the importance and value of empirically assessing the
      need for changes in the recommended nurse staffing levels to develop appropriate,
      realistic and effective policies.

PMID- 24112249
TI  - Immunotherapy following relapse of acute leukaemia after T-cell-replete
      allogeneic peripheral blood progenitor cell transplantation: importance of new
      onset chronic graft-versus-host disease.
AB  - INTRODUCTION: To further define the relative impact of immunotherapy and
      subsequent development of graft-versus-host disease (GVHD) on survival in
      patients with relapsed acute leukaemia postallogeneic hematopoietic stem cell
      transplant (SCT), we performed a single-centre retrospective analysis of 32
      actively treated patients between 2003 and 2011. METHODS: A total of 13 patients
      were identified who were treated actively with cessation of immunosuppression +/-
      Fludarabine, Cytarabine, G-CSF (FLAG) induction, but no donor leucocyte infusion
      (DLI) (non-DLI group) and 19 patients received the same step-wise therapy plus G
      CSF mobilized DLI (G-DLI group). RESULTS: Groups were not statistically different
      with regards to baseline characteristics; however, the G-DLI group contained more
      sibling donors as opposed to unrelated donors than the non-DLI group. With a
      median follow-up of 47 months, the median overall survival (OS) of the non-DLI
      and G-DLI groups was not statistically different (8 months vs. 9 months,
      respectively, P = 0.5). Survival at 3 years was <10% in both groups. Univariate
      analysis identified response to FLAG, and new onset chronic GVHD as the only
      factors associated with improved OS. CONCLUSION: Second donor stem cell infusions
      are unwarranted in the treatment of relapse after allogeneic SCT and therapeutic
      strategies should focus on cytoreduction followed by immune modulation with the
      aim of invoking chronic GVHD.

PMID- 24112250
TI  - Clinical reasoning and dual mental processing in diagnostic competence.

PMID- 24112251
TI  - Learning from errors in radiology to improve patient safety.
AB  - OBJECTIVE: To determine the views and practices of trainees and consultant
      radiologists about error reporting. STUDY DESIGN: Cross-sectional survey. PLACE
      AND DURATION OF STUDY: Radiology trainees and consultant radiologists in four
      tertiary care hospitals in Karachi approached in the second quarter of 2011.
      METHODOLOGY: Participants were enquired as to their grade, sub-specialty
      interest, whether they kept a record/log of their errors (defined as a mistake
      that has management implications for the patient), number of errors they made in
      the last 12 months and the predominant type of error. They were also asked about
      the details of their department error meetings. All duly completed questionnaires
      were included in the study while the ones with incomplete information were
      excluded. RESULTS: A total of 100 radiologists participated in the survey. Of
      them, 34 were consultants and 66 were trainees. They had a wide range of sub
      specialty interest like CT, Ultrasound, etc. Out of the 100 responders, 49 kept a
      personal record/log of their errors. In response to the recall of approximate
      errors they made in the last 12 months, 73 (73%) of participants recorded a
      varied response with 1 - 5 errors mentioned by majority i.e. 47 (64.5%). Most of
      the radiologists (97%) claimed receiving information about their errors through
      multiple sources like morbidity/mortality meetings, patients' follow-up, through
      colleagues and consultants. Perceptual error 66 (66%) were the predominant error
      type reported. Regular occurrence of error meetings and attending three or more
      error meetings in the last 12 months was reported by 35% participants. Majority
      among these described the atmosphere of these error meetings as informative and
      comfortable (n = 22, 62.8%). CONCLUSION: It is of utmost importance to develop a
      culture of learning from mistakes by conducting error meetings and improving the
      process of recording and addressing errors to enhance patient safety.

PMID- 24112252
TI  - Adrenocortical response to 17-beta estradiol replacement in oophorectomized
      female sprague dawley rats.
AB  - OBJECTIVE: To determine the effect of estradiol treatment on serum corticosterone
      levels in Oophorectomized (OVX) female Sprague Dawley rats exposed to chronic
      restraint stress. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY:
      Department of Physiology, Army Medical College, Rawalpindi and National Institute
      of Health, Islamabad, from January to December 2008. METHODOLOGY: A total of 90
      female Sprague Dawley rats (age: 90 +/- 10 days), were divided into three groups,
      each having 30 rats. Group-I comprised of healthy control female rats whereas
      group-II and III were experimental female rats exposed to chronic restraint
      stress after bilateral Oophorectomy and called estradiol treated and vehicle
      treated groups. Estradiol treatment of Oophorectomized rats was done once daily
      for 2 weeks. At the end of experiment, the rats were sacrificed and intracardiac
      blood sampling was done to measure serum corticosterone levels by enzyme linked
      immunosorbent assay (ELISA) kit. RESULTS: The restraint stress to estradiol
      treated rats for 2 weeks revealed that serum corticosterone levels were
      significantly increased (31.32 +/- 5.46 ng/ml, p < 0.05) as compared to the
      healthy controls (17.48 +/- 4.14 ng/ml). CONCLUSION: Chronic restraint stress
      results increases the serum corticosterone levels in Oophorectomized Sprague
      Dawley rats. Estradiol treatment increases the responsiveness of adrenal cortex
      of Oophorectomized female rats.

PMID- 24112253
TI  - Hepatocellular carcinoma after sustained viral response to interferon and
      ribavirin therapy in cirrhosis secondary to chronic hepatitis C.
AB  - OBJECTIVE: To determine the frequency of development of hepatocellular carcinoma
      in patients with chronic liver disease secondary to hepatitis C who had achieved
      sustained virological response with Interferon and Ribavirin therapy. STUDY
      DESIGN: Retrospective descriptive study. PLACE AND DURATION OF STUDY: Shifa
      International Hospital, Islamabad, Pakistan, from January 2007 to January 2012.
      METHODOLOGY: Hepatitis C related chronic liver disease patients who were treated
      with interferon and ribavirin, after they achieved sustained virological
      response, they were followed for a mean of 42 +/- 17 months. During this time,
      development of hepatocellular carcinoma was ascertained. All underwent
      surveillance with alpha-feto-protein and ultrasonography every 6 months. RESULTS:
      Out of the 58 patients who had achieved sustained virological response, 3
      developed hepatocellular carcinoma after a mean follow-up of 38 +/- 14 months. It
      was multifocal in 2 cases and was single lesion in the 3rd. Two patients
      ultimately died, one with upper GI bleeding and the other with hepatic
      encephalopathy, while 3rd patient with single lesion is still surviving.
      CONCLUSION: Three out of 58 patients of hepatitis C related chronic liver disease
      developed hepatocellular carcinoma during follow-up in patients who had achieved
      sustained virological response. These patients need closer follow-up, for
      development of complications, even if they have achieved sustained viral
      response.

PMID- 24112254
TI  - Antibiotic therapy in pyogenic meningitis in paediatric patients.
AB  - OBJECTIVE: To isolate and identify the causative pathogen, antibiotic sensitivity
      testing and success rate of empirical antibiotic therapy in pyogenic meningitis.
      STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: The Children's
      Hospital and Institute of Child Health, Lahore, Pakistan, from March to July
      2012. METHODOLOGY: The study was performed on 72 culture positive meningitis
      cases in children less than 15 years of age. This therapy was evaluated by
      monitoring the patient's clinical picture for 14 - 21 days. The collected data
      was analyzed by Chi-square test. RESULTS: Seventeen different bacteria were
      isolated. The most commonly occurring bacteria were coagulase negative
      Staphylococci (25%), E. coli (12.5%), Klebsiella pneumoniae (8.3%), Streptococcus
      pneumoniae (8.3%) and Pseudomonas aeruginosa (8.3%). All the bacteria were
      sensitive to vancomycin (96.7%), meropenem (76.7%), amikacin (75%), ciprofloxacin
      (65.3%), chloramphenicol (46.5%), ceftazidime (44.2%), cefepime (41.9%), co
      amoxiclav (38.0%), oxacillin (34.8%), cefotaxime (21.4%), penicillin (20.7%),
      ceftriaxone (18.6%), cefuroxime (14%) and ampicillin (6.9%). The combination of
      sulbactam and cefoperazone showed antimicrobial sensitivity of 81.4%. The success
      rate of empirical antibiotic therapy was 91.7%. CONCLUSION: It was found that
      Gram negative bacteria were the major cause of pyogenic meningitis. Mostly there
      were resistant strains against all commonly used antibiotics except vancomycin.
      All empirical antibiotic therapies were found to be most successful.

PMID- 24112255
TI  - Frequency and treatment of methicillin resistant Staphylococcus aureus in
      obstetric and gynaecological sepsis.
AB  - OBJECTIVE: To perform culture and sensitivity for pathogens causing puerperal and
      postoperative wound sepsis and determine the frequency of Methicillin Resistant
      Staphylococcus aureus (MRSA) in such infections. STUDY DESIGN: Observational
      study. PLACE AND DURATION OF STUDY: Obstetrics and Gynaecology Ward, Jinnah
      Postgraduate Medical Centre, Karachi, from December 2008 to May 2010.
      METHODOLOGY: All patients presenting with puerperal sepsis or postoperative wound
      infection were enrolled. Pus was collected for culture and sensitivity using
      standard technique. Two samples were taken from each patient; one before starting
      the treatment and one at the end of treatment. Ames transport medium was used.
      Empirical treatment with triple regimen (Ampicillin, Metronidazole and
      Gentamicin) was started immediately to cover Gram positive as well as negative
      bacteria in addition to anaerobic infection. After receiving the sensitivity
      report, antimicrobial agent were changed accordingly. Samples from ward and
      theater staff and environment were also taken to look for possible mode of
      transmission. Data was recorded on a proforma. Discrete variables are expressed
      as percentages. RESULTS: Staphylococcus aureus was the most frequent organism
      isolated in 34.6% cases. Methicillin sensitive Staphylococcus aureus was seen in
      20% cases and methicillin resistant Staphylococcus aureus was seen in 14.6%. Out
      of these 14.6% MRSA, (17) 77% was associated with puerperal sepsis and rest (5)
      23% was associated with postoperative wound infection. It showed best sensitivity
      to vancomycin. CONCLUSION: Staphylococcus aureus and E. coli were common
      causative agent of postoperative infections and puerperal sepsis.

PMID- 24112256
TI  - Fetomaternal outcome with hepatitis e in pregnancy.
AB  - OBJECTIVE: To assess the maternal morbidity and mortality and fetal outcome with
      hepatitis E (HEV) in pregnancy. STUDY DESIGN: Cross-sectional study. PLACE AND
      DURATION OF STUDY: Liaquat National Hospital, Karachi, from May 2008 to April
      2010. METHODOLOGY: Thirty patients admitted at Gynae Ward with serologically
      proven HEV in pregnancy were included in the study. All these patients were
      followed during their hospital stay with liver function tests and coagulation
      profile. Maternal morbidity and mortality and fetal outcome were recorded.
      RESULTS: Maximum maternal morbidities were noted in patients who presented in 3rd
      trimester, both clinically and derangement of haematological and biochemical
      tests. Out of 30 patients, 08 patients expired with maternal mortality rate of
      29.3% and rest were discharged safely. Perinatal mortality rate was 30.3 per 1000
      live births. CONCLUSION: Hepatitis E runs a fulminant course during pregnancy
      with very high mortality rate especially during third trimester and postpartum
      period.

PMID- 24112257
TI  - Impact of discharge timings of healthy newborns on the rates and etiology of
      neonatal hospital readmissions.
AB  - OBJECTIVE: To evaluate the effect of early hospital discharge after initial birth
      hospitalization on the rate and etiology of hospital readmissions during the
      neonatal period. STUDY DESIGN: Cross-sectional analytical study. PLACE AND
      DURATION OF STUDY: King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi
      Arabia, from October 2008 to September 2011. METHODOLOGY: Full-term normal
      newborns were included in this study, and all infants showing any features that
      would increase the chances of readmission were excluded. Initial birth
      hospitalization and readmission in the neonatal period were analyzed. Data was
      collected from the Discharge Abstract Database. RESULTS: Overall, 12,728 normal
      newborns were delivered during the study period. Vaginally delivered infants were
      discharged early (within 48 hours), while those delivered via caesarean section
      had longer hospital stays (mean length of stay: 1.1 and 2.8 days, respectively).
      There were 166 readmissions, wherein the leading cause was neonatal sepsis
      (37.3%) followed by neonatal jaundice (26.5%). The readmission rate in early
      discharged (142 out of 9927) was significantly higher (p = 0.017) as compared to
      newborns who were discharged late after birth (24 out of 2801). Etiology of
      readmissions was not affected by discharge timings. CONCLUSION: Hospital
      discharge of neonates within 48 hours after delivery is counterproductive and
      significantly increases the risk for hospital readmission during the neonatal
      period. The pre-dominance of sepsis-related cases observed here indicates the
      need to explore its causes and determine an optimal prevention and management
      strategy.

PMID- 24112258
TI  - Six-minute walk test performance in healthy adult Pakistani volunteers.
AB  - OBJECTIVE: To determine the six-minute walking distance (6MWD) for healthy
      Pakistanis, identify factors affecting 6MWD, compare published equations with the
      local data and derive an equation. STUDY DESIGN: Cross-sectional study. PLACE AND
      DURATION OF STUDY: Two medical institutes of Karachi, from January to May 2011.
      METHODOLOGY: Subjects between 15 and 65 years were prospectively enrolled after
      screening. A standardized 6MWT was administered. SpO2, HR, BP and dyspnoea scores
      were determined pre- and post-test. RESULTS: Two hundred and eleven (71%) men and
      85 (29%) women participated. Mean 6MWD was 469.88 +/- 101.24 m: men walked 502.35
      +/- 92.21 m and women walked 389.28 +/- 74.29 m. On univariate analysis, gender,
      height, weight and age showed a significant relationship with the 6MWD. Gender
      and age were identified as independent factors in multiple regression analysis,
      and together explained 33% of the variance. The gender-specific prediction
      equations were: 6MWD (m) for men = 164.08 + (78.06*1) - (1.90*age in years) +
      (1.95*height in cms) 6MWD (m) for women = 164.08 - (1.90*age in years) +
      (1.95*height in cms). CONCLUSION: 6MWDs among the volunteer subjects were shorter
      than predicted by reference equations in literature. Height, gender and weight
      combined explained 33% of the variance. The moderate over-estimation of the 6MWD
      in Pakistani subject. The proposed equation gives predicted (mean) 6MWDs for
      adult Pakistani naive to the test when employing standardized protocol.

PMID- 24112259
TI  - Extracorporeal shock wave lithotripsy (ESWL) vs. ureterorenoscopic (URS)
      manipulation in proximal ureteric stone.
AB  - OBJECTIVE: To compare the stone free rate at one week after extracorporeal shock
      wave lithotripsy (ESWL) and ureterorenoscopic (URS) manipulation for proximal
      ureteric stone (10 - 15 mm size). STUDY DESIGN: Randomized controlled trial.
      PLACE AND DURATION OF STUDY: Sindh Institute of Urology and Transplantation
      (SIUT), Karachi, from August 2010 to February 2011. METHODOLOGY: One hundred and
      ninety patients with 10 - 15 mm proximal urteric stone, in each group were
      treated with ESWL and ureterorenoscopic manipulation by using an 8.0 or 8.5 Fr
      semi rigid ureteroscope. Intracorporeal lithotripsy was performed by using
      pneumatic lithoclast. The stone free rate were compared between groups by
      considering size of stone at one week after procedure. The success rate,
      retreatment rate, auxiliary procedure and complication rate were compared in each
      group. RESULTS: Success rate was 49.2% for ESWL and 57.8% for URS (p = 0.008).
      The re-treatment rate was significantly higher in ESWL group than in URS group
      (40% vs. 11 and 18% in URS group). CONCLUSION: Although ESWL is regarded as the
      preferred choice of treatment for proximal ureteric stone, the present results
      suggest that ureterorenoscopic manipulation with intracorporeal lithotripsy is a
      safe alternative, with an advantage of obtaining an earlier or immediate stone
      free status. Laparoscopic approaches are reasonable alternatives in cases, where
      ESWL and URS have failed.

PMID- 24112260
TI  - Is photodynamic therapy with adjunctive non-surgical periodontal therapy
      effective in the treatment of periodontal disease under immunocompromised
      conditions?
AB  - The aim was to assess whether or not photodynamic therapy (PDT) with adjunctive
      scaling-and-root-planing (SRP) is effective in the treatment of periodontitis
      under immunocompromised conditions. PubMed/Medline and Google-Scholar databases
      were searched from 1967 to May 2013 using various key words. Six studies (five
      experimental and one clinical) were included. In the clinical study, SRP with PDT
      was reported to be ineffective in treating chronic periodontitis in T2DM
      patients. All experimental studies reported significantly less bone loss in
      periodontal defects treated with SRP+PDT than those treated with SRP alone.
      Efficacy of PDT+SRP in the treatment of periodontal disease under
      immunocompromised conditions remains unclear. 

PMID- 24112261
TI  - Autologous serum eye drops for the treatment of persistent corneal epithelial
      defects.
AB  - A series of 10 patients at Armed Forces Institute of Ophthalmology, Rawalpindi,
      from September 2009 to August 2010 is reported. Follow-up of patients were done
      till February 2012. Patients with persistent corneal epithelial defects (PED) of
      minimum 2 weeks duration, in whom conventional therapy had failed, were included
      in the study. They were prescribed 100% autologous serum eye drops on hourly
      basis. When PED healed within 02 weeks, it was labeled as effective and when it
      healed within one month, it was labeled as partially effective. Six weekly follow
      up was done for 18 months for all patients to document any recurrence of PED.
      Eight out of 10 patients had successful outcome i.e. 80% of PED healed within one
      month, out of which 7 patients had 'effective' outcome. Autologous serum eye
      drops are safe, effective and minimally invasive modality in treating PED. 

PMID- 24112262
TI  - Vogt Koyanagi Harada disease: treatment and visual prognosis.
AB  - Vogt Koyanagi Harada (VKH) disease is a chronic, bilateral, granulomatous
      panuveitis associated with central nervous system, auditory and integumentary
      manifestations. The study was conducted from January 2001 to December 2010 at the
      Department of Ophthalmology, Khyber Teaching Hospital, Peshawar. A total of 9
      patients with diagnosis of Vogt Koyanagi Harada disease were included in the
      study. Extracted data included age, gender, duration of disease, initial and
      final visual acuities, treatment and complications. Initial visual acuity was
      ranging from 6/24 to perception of light. All the patients were treated with
      systemic and topical corticosteroids. In addition, one patient also received
      cytotoxic therapy. Final visual acuity was 6/18 or better in all cases (100%).
      One patient developed bilateral cataract, glaucoma and subretinal fibrosis at the
      macula. The cataract and glaucoma were managed as per established protocols. The
      visual prognosis of Vogt Koyanagi Harada disease is generally favourable if the
      disease is identified early and adequately treated and the associated
      complications are addressed properly. 

PMID- 24112263
TI  - Anomalous origin of left coronary artery from pulmonary artery (ALCAPA).
AB  - Anomalous origin of the left coronary artery from the pulmonary artery also
      recognized as Bland White Garland syndrome is a very rare congenital condition. A
      two-months old baby boy presented with dyspnoea for two weeks and a pansystolic
      murmur on auscultation. The base line investigations showed cardiomegaly and
      bilateral basal haze on X-ray chest. ECG showed ST elevation in leads l and AVl
      and echocardiography showed situs solitus, levocardia, hypokinetic
      intraventricular septum, ejection fraction of 30%, mitral regurgitation of grade
      I and an anomalous origin of the left coronary artery from pulmonary artery was
      diagnosed. Patient was in left heart failure. It was rectified surgically by
      creating a transpulmonary tunnel (Takeuchi repair). Postoperative course was
      uneventful and he was finally discharged in stable condition. 

PMID- 24112264
TI  - Atrioventricular and interventricular groove and septal extension of right sinus
      of valsalva aneurysm: a rare cause of complete heart block.
AB  - A 26 years old male presented with vertigo and history of fall. The
      electrocardiogram revealed 2:1 second-degree heart block and later progression to
      complete heart block. Transthoracic echocardiography revealed aneurysm at the
      site of ascending aorta and computed tomographic scan showed an aneurysm of right
      sinsus of Valsalva extending into right atrioventricular and interventricular
      groove and causing complete heart block by compression on the conduction system.
      He also suffered from lymph node tuberculosis. This case report is unique because
      of rare presentation as complete heart block. 

PMID- 24112265
TI  - Brain tuberculomas mimicking intracranial metastasis in a patient presenting with
      fits.
AB  - Brain tuberculosis is still prevalent in many developing countries, especially
      Asian countries. Tuberculomas should always be considered in the differential
      diagnosis of enhancing intra-axial lesions of the brain. Brain tuberculomas can
      present in many different clinical and radiological patterns clinically like
      headache, fits, cranial nerve palsies and very rarely as brain tuberculomas. We
      describe the case of a 48 years old male patient presenting with persistent
      headache and fits, referred for workup of brain metastasis or primary brain
      neoplasm. On further imaging, it turned out to be multiple tuberculomas of brain
      which resolved on anti-tuberculous treatment along with symptoms relief. 

PMID- 24112266
TI  - Primary embryonal rhabdomyosarcoma of the liver in a young male.
AB  - Rhabdomyosarcoma (RMS) occurs infrequently in the liver. Rhabdomyosarcomas are
      malignant tumours that display features of striated muscle differentiation. They
      are the most common soft-tissue sarcomas among children. In adults however, these
      are very rare. We report a case of a primary embryonal rhabdomyosarcoma of the
      liver in a 17 years old boy. This was confirmed by histological examination using
      immunohistochemical analysis (LCA negative, desmin positive, myogenin focally
      positive and cytokeratin negative) and site was confirmed by PET CT scan. He
      received multiple chemotherapies including (doxorubicin, ifosfamide, dacarbazine;
      gemcitabine, paclitaxel; vincristine, actinomycin D, cyclophosphamide) but
      longest sustained stable disease was seen with gemcitabine-paclitaxel regimen.
      The patient died 31 months after the first presentation, secondary to complicated
      abundant abdominal progressive disease. The poor prognosis and early death of
      most previously reported cases imply the need for investigation of a more
      effective treatment method of this uncommon tumour. 

PMID- 24112267
TI  - Diagnosis and treatment of Hodgkin's lymphoma: at times a challenge.
AB  - Hodgkin's lymphoma has been traditionally defined as a hematopoietic neoplasm
      composed of diagnostic Reed-Sternberg cells. More than 70% of the cases involve
      cervical or supraclavicular lymph nodes. Isolated sub-diaphragmatic
      lymphadenopathy or organ involvement is rare. We present the case of Hodgkin's
      lymphoma in a 51 years old female, who presented with obstructive jaundice and
      lymphadenopathy, empirically treated previously as a case of tuberculosis.
      Chemotherapy with modified ABVD protocol was given with dose modification
      according to LFT's. Her liver functions returned to normal levels after the first
      cycle. The main purpose of reporting the case is to stress definitive diagnosis
      of the disease before initiating treatment and the modified chemotherapy regimen
      used in this infrequent presentation of the disease. 

PMID- 24112268
TI  - Primary chondrosarcoma of breast.
AB  - Mammary sarcomas are heterogeneous group of malignant neoplasms that arise from
      the mammary stroma. They are uncommon tumours and most of these occur as a
      component of other tumours. Of the malignant breast mesenchymal tumours, pure
      sarcomas which lack epithelial component are rarer as these comprise only 0.5% of
      the breast tumours. Of these, the most common are angiosarcomas, liposarcomas and
      osteosarcomas. Pure, primary and De novo chondrosarcomas features as one of the
      rarer types of sarcomas of breast and should be differentiated from Phylloides
      tumours with chondromatous areas by extensive sampling which also excludes ductal
      elements in the tumour. This case report describes very rare primary breast
      sarcoma i.e. chondrosarcoma in a female aged 40 years which was treated by simple
      mastectomy. 

PMID- 24112269
TI  - Xeroderma pigmentosum with melanoma of face and its prosthetic management.
AB  - Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous,
      ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also
      its secondary characters. This case report is about maxillofacial prosthetic
      management of a 10 years old child presented with xeroderma pigmentosum. The nose
      of the patient was excised surgically due to melanoma. This case report
      elaborates the role of prosthodontist and the whole procedure of constructing the
      nasal prosthesis via conventional technique by using the patient's sibling nasal
      form as template. Regular follow up revealed marked improvement in esthetics,
      function and ultimately patient's quality of life. 

PMID- 24112270
TI  - An unsuspected bleeding Meckel's diverticulum in an adult detected on mesenteric
      angiography.
AB  - Meckel's diverticulum is usually asymptomatic and found in almost 2% of the
      population. Haemorrhage from a Meckel's diverticulum is common in children but
      rare in adults. Here we report a case of 20 years old male with recurrent
      gastrointestinal bleeding. Meckel's diverticulum was diagnosed due to abnormal
      vascularity on mesenteric angiography and embolization was performed. Diagnosis
      was correlated with other radiological imaging and later elective resection was
      performed. This case is reported to emphasize the potential role of mesenteric
      angiography in the detection and management of bleeding Meckel's diverticulum and
      correlation with other radiological imaging. 

PMID- 24112271
TI  - Patient communication in radiology: current status of breaking bad news among
      radiologists and radiology trainees in Pakistan.
AB  - Breaking bad news can be an intimidating task for any physician. The aim of this
      study was to record the practices of breaking bad news to the patients by
      Pakistani radiologists and trainees. The radiologists and trainees attending the
      26th National Radiological Conference in October 2010 in Karachi, Pakistan, were
      surveyed. The response rate was 76%. The respondents included residents (51%),
      private practicing radiologists (28%), academic radiologists (13%), and other
      trainees (8%). Most of the academic radiologists communicated with their
      patients. The daily frequency of breaking bad news by residents was noted, which
      was highest in the public teaching hospitals (71%). For severe abnormalities such
      as malignancy, 50% residents, 55% of the academic radiologists and 74% of the
      private practicing radiologists were very uncomfortable in disclosure of results.
      Differences in frequency of communication with patients were noticed with both
      different training levels, and different settings of practice in a developing
      country. 

PMID- 24112272
TI  - End of treatment response in chronic hepatitis C patients treated with interferon
      alpha and ribavirin.
AB  - We conducted a study at Combined Military Hospital (CMH), Sialkot, from August
      2010 to February 2011 with the objective to determine the frequency of early and
      end of treatment virological response in patients with chronic hepatitis C
      infection treated with IFN-a / ribavirin therapy. HCV RNA PCR positive adult
      patients of either gender were included in the study. A total of 123 patients (56
      males and 67 females) were given alpha-interferon ribavirin for 24 weeks. At 12
      weeks posttreatment, 82 patients out of 123 (EVR 66.6%) had negative HCV RNA PCR
      while 85 patients out of 123 were HCV PCR negative at 24 weeks (ETR 69.1%).
      Conventional alpha-interferon ribavirin therapy should be discontinued in
      patients who are non responders at 12 weeks of treatment and be offered pegylated
      interferon to save time, money and minimize the side effects. 

PMID- 24112273
TI  - Breast cancer.

PMID- 24112274
TI  - Congenital pubic sinus: clarified nomenclature.

PMID- 24112275
TI  - Mitogen-activated protein kinase phosphatase 1 as an inflammatory factor and drug
      target.
AB  - Mitogen-activated protein kinases (MAPKs) are signaling proteins that are
      activated through phosphorylation, and they regulate many physiological and
      pathophysiological processes in cells. Mitogen-activated protein kinase
      phosphatase 1 (MKP-1) is an inducible nuclear phosphatase that dephosphorylates
      MAPKs, and thus, it is a negative feedback regulator of MAPK activity. MKP-1 has
      been found as a key endogenous suppressor of innate immune responses, as well as
      a regulator of the onset and course of adaptive immune responses. Altered MKP-1
      signaling is implicated in chronic inflammatory diseases in man. Interestingly,
      MKP-1 expression and protein function have been found to be regulated by certain
      anti-inflammatory drugs, namely by glucocorticoids, antirheumatic gold compounds
      and PDE4 inhibitors, and MKP-1 has been shown to mediate many of their anti
      inflammatory effects. In this Mini Review, we summarize the effect of MKP-1 in
      the regulation of innate and adaptive immune responses and its role as a
      potential anti-inflammatory drug target and review recent findings concerning the
      role of MKP-1 in certain anti-inflammatory drug effects. 

PMID- 24112276
TI  - Qualitative evaluation of the SMART2 self-management system for people in chronic
      pain.
AB  - PURPOSE: Technology could support the self-management of long-term health
      conditions such as chronic pain. This article describes an evaluation of SMART2,
      a personalised self-management system incorporating activity planning and review,
      feedback on behaviour- and acceptance-based therapeutic exercises. METHOD: The
      SMART2 system was evaluated over a four-week trial in the homes of people in
      chronic pain. At conclusion, participants were interviewed to understand the
      experience of using and living with the SMART2 system as a therapeutic tool.
      RESULTS: Qualitative analysis of the interviews found that participants liked the
      system and reported making associated changes to their behaviour. Goal setting
      and feedback were the most useful elements of the system. A third key and
      unexpected element was that by simulating some of the functions of a therapist,
      SMART2 also simulated some of the process of interacting with a therapist.
      CONCLUSIONS: People in chronic pain may experience positive outcomes when using a
      self-management system designed for behaviour change. Furthermore, some of the
      supportive aspects of the therapeutic context can be elicited by self-management
      technologies. Implications of Rehabilitation Self-management technology has the
      potential to assist rehabilitation by supporting goal setting and providing
      feedback. By simulating some of the functions of a therapist, technology can
      simulate some of the process of therapy during rehabilitation. People in chronic
      pain liked using the technology in their own home and thought it could augment
      services delivered by clinical practitioners. Complex programmes of therapeutic
      exercises delivered by technology had limited success in engaging people in
      chronic pain.

PMID- 24112277
TI  - Involving patients in clinical research: the Telescot Patient Panel.
AB  - BACKGROUND: To date, patient involvement in the development of clinical research
      work has been limited. In 2011, the Telescot research team commenced work on a
      feasibility trial to investigate home telemonitoring of blood pressure for people
      who have experienced stroke or transient ischaemic attack (TIA). The team decided
      to involve patients in the development of the research. OBJECTIVES: To improve
      research design through patient involvement. METHOD OF PATIENT INVOLVEMENT: A
      modified form of the 'Scrutiny Panel' approach was used to involve people who had
      stroke in the research project. RESULTS: The Patient Panel supported the research
      in three key ways: it informed patient communication; it presented patient
      perspectives on the applicability and usability of the intervention; and it
      guided the development of the qualitative study. DISCUSSION: The initiative was
      considered a positive experience for all. However, challenges were identified in
      terms of the time and cost implications of undertaking patient involvement.
      IMPLICATION FOR RESEARCH PRACTICE: Importance is attached to adequate project
      planning and development, partnership working with community-based organizations
      and the necessity for clear role delineation between patients and professionals
      to enable effective collaborative working. CONCLUSIONS: The Telescot Patient
      Panel was beneficial in supporting the development of the feasibility trial. The
      Panel approach was considered transferable to other clinical research contexts.

PMID- 24112278
TI  - Free-living Waterfowl as a Source of Zoonotic Bacteria in a Dense Wild Bird
      Population Area in Northeastern Spain.
AB  - Salmonella spp. and Campylobacter spp. are zoonotic bacteria that represent an
      economic and public health concern worldwide. Due to the difficulty to collect
      samples from free-living waterfowl, little is known on their importance as a
      reservoir of zoonotic agents. Thus, a study was conducted to determine the
      prevalence, genotypic diversity and antimicrobial susceptibility of Salmonella
      and Campylobacter from waterfowl in Ebro Delta (northeastern Spain), a
      geographical area with a dense wild bird population. Samples were collected from
      318 adult waterfowl belonging to nine fowl species. All the samples were taken
      during the hunting season from 2008 to 2010. None of the birds were positive for
      Salmonella, while the overall Campylobacter prevalence was 12.58% (40/318). A
      much higher Campylobacter coli prevalence than Campylobacter jejuni was found
      (11.64% versus 0.94%). The species Fulica atra showed the highest Campylobacter
      prevalence (78.05%). ERIC-PCR of the isolates showed a high diversity of strains.
      Antimicrobial susceptibility testing of Campylobacter isolates showed that all
      the isolates were susceptible to the seven antibiotics tested.

PMID- 24112279
TI  - Globus pallidus internus oscillatory activity is related to movement speed.
AB  - Local field potentials (LFPs) recorded from deep brain stimulation electrodes
      implanted in the globus pallidus internus (GPi) of patients with hyperkinetic
      movement disorders (dystonia and Tourette's syndrome) have shown desynchronized
      activity at 8-20 Hz and synchronized activity at 30-90 Hz during voluntary
      movements. However, the impact of the speed of the motor task on these frequency
      shifts is still unclear. In the current study, we recorded LFPs bilaterally from
      the GPi in seven patients with hyperkinetic movement disorders during normal/slow
      and fast horizontal line drawing movements as well as during rest. In comparison
      with rest, the low beta band showed a significant decrease in power during the
      motor tasks. Low beta power was more suppressed with increasing speed of the
      movement on the contralateral side. In contrast, a significant increase in power
      was induced by movements in the high beta and gamma bands on the contralateral
      side. When comparing slow and fast movements, the power of the low gamma
      frequency band was significantly elevated on the contralateral side with fast
      movements. In conclusion, an increase in movement speed changes the power of GPi
      oscillations by means of a reduction of the activity in the low beta band and an
      elevation of activity in the gamma band. The current study yields new insights
      into the physiological mechanism of GPi during the execution of the motor task at
      low and high speed. 

PMID- 24112280
TI  - Comparison of four methods for assessing the importance of attitudinal beliefs:
      an international Delphi study in intensive care settings.
AB  - OBJECTIVES: Behaviour change interventions often target 'important' beliefs. The
      literature proposes four methods for assessing importance of attitudinal beliefs:
      elicitation frequency, importance ratings, and strength of prediction (bivariate
      and multivariate). We tested congruence between these methods in a Delphi study
      about selective decontamination of the digestive tract (SDD). SDD improves
      infection rates among critically ill patients, yet uptake in intensive care units
      is low internationally. METHODS: A Delphi study involved three iterations
      ('rounds'). Participants were 105 intensive care clinicians in the United
      Kingdom, Canada, and Australia/New Zealand. In Round 1, semi-structured
      interviews were conducted to elicit beliefs about delivering SDD. In Rounds 2 and
      3, participants completed questionnaires, rating agreement and importance for
      each belief-statement (9-point Likert scales). Belief importance was assessed
      using elicitation frequency, mean importance ratings, and prediction of global
      attitude (Pearson's correlations; beta-weights). Correlations between indices
      were computed. RESULTS: Participants generated 14 attitudinal beliefs. Indices
      had adequate variation (frequencies: 4-94, mean importance ratings: 4.93-8.00,
      Pearson's correlations: +/- 0.09 to +/- 0.54, beta-weights: +/- 0.01 to +/-
      0.30). SDD increases antibiotic resistance was the most important belief
      according to three methods and was ranked second by beta-weights (behind Overall,
      SDD benefits patients to whom it is delivered). Spearman's correlations were
      significant for importance ratings with frequencies and correlations. However,
      other indices were unrelated. The top four beliefs differed according to the
      measure used. CONCLUSIONS: Results provided evidence of congruence across three
      methods for assessing belief importance. Beta-weights were unrelated to other
      indices, suggesting that they may not be appropriate as the sole method.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Attitudinal
      beliefs (specific beliefs about the consequences of performing an action) are key
      to designing interventions to change intentions and behaviour. The literature
      reports four methods for assessing the importance of attitudinal beliefs:
      frequency of elicitation in interviews, importance ratings in questionnaires, and
      strength of prediction (bivariate and multivariate) of global attitude scores.
      The congruence between these measures of importance is not known. What does this
      study add? Four indices of importance were examined in a multi-professional,
      international study about the use of selective digestive decontamination to
      prevent infection in intensive care settings. Three indices were correlated with
      one another. Each method used to assess importance produced a different subset of
      the most important beliefs. Selection of the most important beliefs should use
      multiple assessment methods. This evidence suggests that multiple regression
      approaches may not be appropriate as the sole method for assessing belief
      importance.

PMID- 24112281
TI  - Descending necrotizing Mediastinitis caused by Kocuria rosea: a case report.
AB  - BACKGROUND: Kocuria species are gram-positive, non-pathogenic commensals.
      However, in immunocompromised patients such as transplant recipients, cancer
      patients, or patients with chronic medical conditions, they can cause
      opportunistic infections. CASE PRESENTATION: We report the first case of
      descending necrotizing mediastinitis in a 58-year-old, relatively healthy woman
      caused by Kocuria rosea. CONCLUSION: Descending necrotizing mediastinitis due to
      Kocuria rosea can be successfully treated with prompt surgical drainage combined
      with antimicrobial therapy.

PMID- 24112282
TI  - Intravenous antibiotics given for 2 weeks do not eradicate persistent
      Staphylococcus aureus clones in cystic fibrosis patients.
AB  - Staphylococcus aureus is the most commonly isolated pathogen in respiratory tract
      secretions from young patients with cystic fibrosis (CF), and several treatment
      strategies are used to control the infection. However, it is not known whether
      intensified treatment with antimicrobial agents causes eradication of S. aureus
      clones. We retrospectively determined the impact of intravenous (IV)
      antimicrobial agents on the suppression and eradication of S. aureus clones. One
      thousand and sixty-one S. aureus isolates cultured from 2526 samples from 130 CF
      patients during a 2-year study period were subjected to spa typing. Intervals
      between positive samples and the occurrence of clone replacements were calculated
      in relation to courses of IV antimicrobial agents. Of 65 patients chronically
      infected with S. aureus, 37 received 139 courses of IV antimicrobial agents with
      activity against S. aureus (mean duration, 15 days; range, 6-31 days).
      Administration of IV antibiotics increased the time to the next sample with
      growth of S. aureus: the mean interval between two positive samples was 68 days
      if IV treatment had been administered, in contrast to 49 days if no IV treatment
      had been administered (p 0.003). When S. aureus recurred in sputum after IV
      treatment, the isolate belonged to a different clone in 33 of 114 (29%)
      intervals, in comparison with 68 of 232 (29%) intervals where IV treatment had
      not been prescribed (OR 0.98, 95% CI 0.60-1.61). In conclusion, we show that 2
      weeks of IV antimicrobial treatment can significantly suppress chronic
      staphylococcal infection in CF, but is not associated with the eradication of
      persistent bacterial clones.

PMID- 24112283
TI  - Application of Lean Methodology for Improved Quality and Efficiency in Operating
      Room Instrument Availability.
AB  - Advances in surgical instrumentation allow surgeons to treat patients with less
      morbidity and shorter recovery time. However, the increasing complexity also adds
      to surgical risk, and to operating room supply chain burden. To improve the
      quality and efficiency of operating room instrument availability, we developed
      and validated a Lean 5S approach consisting of sort (determining instrument usage
      and waste), simplify (removing unnecessary instruments), sweep (confirm
      availability of needed instruments), standardize (all trays the same for a given
      procedure), and self-discipline (monitor success). The primary outcome was
      reduction in unnecessary instruments delivered to the operating room. As a
      secondary analysis, we evaluated the effect of the Lean instrument intervention
      on surgery times. We reduced the number of instruments for minimally invasive
      spine surgery by 70% (from 197 to 58), and setup time decreased 37% (13.1-8.2
      min, p = .0015). We also report subsequent validation of the approach on deep
      brain stimulator cases. We conclude that complex surgical procedures offer
      opportunities for substantial waste reduction, simplification, and quality
      improvement, with potential institutional annual cost savings of $2.8 million. We
      demonstrate that Lean methodology can improve quality at lower cost. 

PMID- 24112284
TI  - Allocation and matching in kidney exchange programs.
AB  - Living donor kidney transplantation is the preferred treatment for patients
      suffering from end-stage renal disease. To alleviate the shortage of kidney
      donors, many advances have been made to improve the utilization of living donors
      deemed incompatible with their intended recipient. The most prominent of these
      advances is kidney paired donation (KPD), which matches incompatible patient
      donor pairs to facilitate a kidney exchange. This review discusses the various
      approaches to matching and allocation in KPD. In particular, it focuses on the
      underlying principles of matching and allocation approaches, the combination of
      KPD with other strategies such as ABO incompatible transplantation, the
      organization of KPD, and important future challenges. As the transplant community
      strives to balance quantity and equity of transplants to achieve the best
      possible outcomes, determining the right long-term allocation strategy becomes
      increasingly important. In this light, challenges include making full use of the
      various modalities that are now available through integrated and optimized
      matching software, encouragement of transplant centers to fully participate,
      improving transplant rates by focusing on the expected long-run number of
      transplants, and selecting uniform allocation criteria to facilitate
      international pools. 

PMID- 24112285
TI  - Toll-like receptor 2 subfamily genotypes are not associated with severity of
      bronchiolitis or postbronchiolitis wheezing in infants.
AB  - AIM: Expression of toll-like receptor (TLR) 2 subfamily genes, including genes
      encoding TLR1, TLR2, TLR6 and TLR10, have been connected to allergy and asthma.
      This controlled study investigated the association of TLR1, TLR2 and TLR6 gene
      polymorphisms with clinical characteristics and subsequent wheezing in young
      infants with bronchiolitis. METHODS: In all, 129 full-term infants hospitalised
      for bronchiolitis at the age of <6 months were clinically followed up until a
      mean age of 18 months. Genotyping of the TLR1 T1805G, TLR2 G2258A and TLR6 C745T
      polymorphisms was carried out by pyrosequencing and in 318 healthy, Finnish
      controls. RESULTS: There were no significant associations between TLR1, TLR2 or
      TLR6 genotypes and severity of bronchiolitis or risk of postbronchiolitis
      wheezing. TLR6 polymorphism was associated with allergy in univariate analyses.
      Minor allele frequency (MAF) in the TLR1 gene (17%) in the hospitalised children
      was similar to our Finnish controls, but different to European controls from
      other studies. MAF in the TLR6 gene was 50% versus 41% in both the Finnish and
      European controls. MAF in the TLR2 gene was low (3%) in study subjects and in
      both controls. CONCLUSION: TLR2 subfamily gene polymorphisms were not associated
      with severity of bronchiolitis or risk of postbronchiolitis wheezing.

PMID- 24112287
TI  - Real-time contrast-enhanced endoscopic ultrasonography-guided fine-needle
      aspiration (with video).

PMID- 24112286
TI  - The level of H2O2 type oxidative stress regulates virulence of Theileria
      transformed leukocytes.
AB  - Theileria annulata infects predominantly macrophages, and to a lesser extent B
      cells, and causes a widespread disease of cattle called tropical theileriosis.
      Disease-causing infected macrophages are aggressively invasive, but this
      virulence trait can be attenuated by long-term culture. Attenuated macrophages
      are used as live vaccines against tropical theileriosis and via their
      characterization one gains insights into what host cell trait is altered
      concomitant with loss of virulence. We established that sporozoite infection of
      monocytes rapidly induces hif1-alpha transcription and that constitutive
      induction of HIF-1alpha in transformed leukocytes is parasite-dependent. In both
      infected macrophages and B cells induction of HIF-1alpha activates transcription
      of its target genes that drive host cells to perform Warburg-like glycolysis. We
      propose that Theileria-infected leukocytes maintain a HIF-1alpha-driven
      transcriptional programme typical of Warburg glycolysis in order to reduce as
      much as possible host cell H2 O2 type oxidative stress. However, in attenuated
      macrophages H2O2 production increases and HIF-1alpha levels consequently remained
      high, even though adhesion and aggressive invasiveness diminished. This indicates
      that Theileria infection generates a host leukocytes hypoxic response that if not
      properly controlled leads to loss of virulence.

PMID- 24112288
TI  - Dementia Care Knowledge Sharing within a First Nations Community.
AB  - This article discusses the First Nations sample of a larger study on dementia
      care decisions and knowledge sharing.The purpose is to enhance understanding of
      the process of knowledge sharing among health care practitioners(HCPs), care
      partners, and persons with dementia (PWDs) within a rural First Nations
      community. A constructivist grounded theory methodology was used. Nineteen
      interviews were conducted at three points in time with two dementia care networks
      that included two PWDs, three care partners, and two HCPs. A sharing dementia
      care knowledge model was conceived, with the PWDs and their care partners at the
      centre. Knowledge sharing in the model was represented by three broad themes: (1)
      developing trusting relationships, (2) accessing and adapting the information,
      and (3) applying the information. Culturally sensitive approaches were essential
      to developing trusting relationships. Once developed, knowledge sharing through
      accessing, adapting, and applying the information was possible.

PMID- 24112289
TI  - Blood flow to the scarred gravid uterus at 22-24 weeks of gestation.
AB  - OBJECTIVE: To compare uterine artery volume blood flow (Q(uta)), vascular
      resistance (R(uta)), pulsatility index (Uta PI), and the fraction of maternal
      cardiac output (CO) distributed to the uteroplacental circulation in pregnant
      women with and without a previous caesarean section. DESIGN: Cross-sectional
      observational study. SETTING: University hospital in Norway. POPULATION: Thirty
      two pregnant women with previous caesarean section and 32 matched controls.
      METHODS: Ultrasonography was used to measure uterine artery diameter and blood
      flow velocity between 22(+0) and 23(+6) weeks of gestation. Impedance
      cardiography was used to assess maternal haemodynamics. MAIN OUTCOME MEASURES:
      Q(uta), R(uta), Uta PI, and the fraction of maternal CO distributed to the
      uteroplacental circulation. RESULTS: The mean Q(uta) was 356.26 +/- 213.72
      ml/minute in cases and 456.41 +/- 209.70 ml/minute in controls (P = 0.038).
      R(uta) was significantly (P = 0.026) higher among cases compared with controls
      (0.32 +/- 0.20 versus 0.22 +/- 0.14 mmHg/ml/minute), but the Uta PI did not
      differ between the groups (0.93 +/- 0.23 versus 0.92 +/- 0.47; P = 0.929). The
      fraction of maternal CO distributed to the uteroplacental circulation was 5.75 +/
      3.68% in cases and 8.45 +/- 5.02% in controls (P = 0.014). CONCLUSIONS: Uterine
      artery volume blood flow and the fraction of maternal cardiac output distributed
      to the uteroplacental circulation are lower, and uterine vascular resistance (but
      not Uta PI) is higher, in women with previous caesarean section compared with the
      control group.

PMID- 24112290
TI  - Pediatric frontal lobe epilepsy: white matter abnormalities and cognitive
      impairment.
AB  - OBJECTIVES: Cognitive impairment is frequent in children with frontal lobe
      epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we
      have studied cerebral white matter properties and associations with cognitive
      functioning in children with FLE and healthy controls. METHODS: Thirty children
      aged 8-13 years with FLE of unknown cause and 39 healthy age-matched controls
      underwent neuropsychological assessment, structural and diffusion-weighted brain
      MRI. Patients were grouped as cognitively impaired or unimpaired, and their white
      matter diffusion properties were compared with the controls. RESULTS: Children
      with FLE had reduced apparent diffusion coefficients in various posteriorly
      located tract bundles, a reduced fractional anisotropy (FA) of the white matter
      tract between the right frontal and right occipital lobe, and smaller volumes of
      several collections of interlobar bundle tracts, compared with controls. The
      cognitively impaired patient group demonstrated significant increases in FA of
      the white matter of both occipital lobes, a reduced FA of white matter tract
      bundles between the right frontal and both left occipital lobe and subcortical
      white matter area, and smaller volumes of two collections of tract bundles
      connecting the frontal lobe with the temporal and parietal lobes, compared with
      controls. CONCLUSIONS: Children with FLE had white matter abnormalities mainly in
      posterior brain regions, not confined to the area of the seizure focus.
      Cognitively impaired children with FLE showed the most pronounced white matter
      abnormalities. These possibly reflect disturbed maturation and might be part of
      the etiology of the cognitive impairment.

PMID- 24112291
TI  - Lymphoma immunophenotype of dogs determined by immunohistochemistry, flow
      cytometry, and polymerase chain reaction for antigen receptor rearrangements.
AB  - BACKGROUND: Immunohistochemistry (IHC), flow cytometry (FC), and PCR for antigen
      receptor rearrangements (PARR) are 3 widely utilized tests to determine
      immunophenotype in dogs with lymphoma (LSA). OBJECTIVES: This study evaluated the
      ability of FC and PARR to correctly predict immunophenotype as defined by IHC and
      to determine the level of agreement among the 3 tests. ANIMALS: Sixty-two dogs
      with lymphoma. METHODS: Retrospective study. Medical records were searched to
      identify dogs with LSA that had concurrent IHC, FC, and PARR performed.
      Immunophenotype results were categorized as B-cell, T-cell, dual immunophenotype
      (B- and T-cell), or indeterminate. The results of FC and PARR were evaluated for
      correctly classifying B- and T-cell LSA as compared with IHC. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      were evaluated in addition to concordance between each test. RESULTS: The
      sensitivity of FC was significantly higher than PARR for both B-cell (91% versus
      67%; P < 0.0072) and T-cell (100% versus 75%; P < 0.0312) LSA. The percent
      agreement between FC and IHC was 94%, between PARR and IHC was 69%, between FC
      and PARR was 63%, and among all 3 tests was 63%. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Flow cytometry is superior to PARR in correctly predicting
      immunophenotype when evaluating lymph nodes from dogs already diagnosed with B-
      or T-cell LSA. If fresh samples are not available for FC, PARR is an acceptable
      assay for determination of immunophenotype given its high specificity.

PMID- 24112292
TI  - Sources of community health worker motivation: a qualitative study in Morogoro
      Region, Tanzania.
AB  - BACKGROUND: There is a renewed interest in community health workers (CHWs) in
      Tanzania, but also a concern that low motivation of CHWs may decrease the
      benefits of investments in CHW programs. This study aimed to explore sources of
      CHW motivation to inform programs in Tanzania and similar contexts. METHODS: We
      conducted semi-structured interviews with 20 CHWs in Morogoro Region, Tanzania.
      Interviews were digitally recorded, transcribed, and coded prior to translation
      and thematic analysis. The authors then conducted a literature review on CHW
      motivation and a framework that aligned with our findings was modified to guide
      the presentation of results. RESULTS: Sources of CHW motivation were identified
      at the individual, family, community, and organizational levels. At the
      individual level, CHWs are predisposed to volunteer work and apply knowledge
      gained to their own problems and those of their families and communities.
      Families and communities supplement other sources of motivation by providing
      moral, financial, and material support, including service fees, supplies, money
      for transportation, and help with farm work and CHW tasks. Resistance to CHW work
      exhibited by families and community members is limited. The organizational level
      (the government and its development partners) provides motivation in the form of
      stipends, potential employment, materials, training, and supervision, but
      inadequate remuneration and supplies discourage CHWs. Supervision can also be dis
      incentivizing if perceived as a sign of poor performance. CONCLUSIONS: Tanzanian
      CHWs who work despite not receiving a salary have an intrinsic desire to
      volunteer, and their motivation often derives from support received from their
      families when other sources of motivation are insufficient. Policy-makers and
      program managers should consider the burden that a lack of remuneration imposes
      on the families of CHWs. In addition, CHWs' intrinsic desire to volunteer does
      not preclude a desire for external rewards. Rather, adequate and formal financial
      incentives and in-kind alternatives would allow already-motivated CHWs to
      increase their commitment to their work.

PMID- 24112293
TI  - Study on combined effects of blanching and sonication on different quality
      parameters of carrot juice.
AB  - This study was conducted to evaluate the combined effects of blanching and
      sonication on carrot juice quality. Carrots were blanched at 100  degrees C for 4
      min in normal and acidified water. Juice was extracted and sonicated at 15 
      degrees C for 2 min keeping pulse duration 5 s on and 5 s off (70% amplitude
      level and 20 kHz frequency). No significant effect of blanching and sonication
      was observed on Brix, pH and titratable acidity except acidified blanching that
      decreased pH and increased acidity significantly. Peroxidase was inactivated
      after blanching that also significantly decreased total phenol, flavonoids,
      tannins, free radical scavenging activity, antioxidant capacity and ascorbic acid
      and increased cloud and color values. Sonication could improve all these
      parameters significantly. The present results suggest that combination of
      blanching and sonication may be employed in food industry to produce high-quality
      carrot juice with reduced enzyme activity and improved nutrition.

PMID- 24112294
TI  - Laser ionization mass spectrometry in oral squamous cell carcinoma.
AB  - Biomarker research in oral squamous cell carcinoma (OSCC) aims for
      screening/early diagnosis and in predicting its recurrence, metastasis and
      overall prognosis. This article reviews the current molecular perspectives and
      diagnosis of oral cancer with proteomics using matrix-assisted laser desorption
      ionization (MALDI) and surface-enhanced laser desorption ionization (SELDI) mass
      spectrometry (MS). This method shows higher sensitivity, accuracy,
      reproducibility and ability to handle complex tissues and biological fluid
      samples. However, the data interpretation tools of contemporary mass spectrometry
      still warrant further improvement. Based on the data available with laser-based
      mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and
      prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug
      targets. Majority of these biomarkers are involved in cell homeostasis and are
      either physiologic responders or enzymes. Therefore, proteins directly related to
      tumorigenesis have more diagnostic value. Salivary secretory markers are another
      group that offers a favourable and easy strategy for non-invasive screening and
      early diagnosis in oral cancer. Key molecular inter-related pathways in oral
      carcinogenesis are also intensely researched with software analysis to facilitate
      targeted drug therapeutics. The review suggested the need for incorporating
      'multiple MS or tandem approaches' and focusing on a 'group of biomarkers'
      instead of single protein entities, for making early diagnosis and treatment for
      oral cancer a reality. 

PMID- 24112295
TI  - A lesson in business: cost-effectiveness analysis of a novel financial incentive
      intervention for increasing physical activity in the workplace.
AB  - BACKGROUND: Recently both the UK and US governments have advocated the use of
      financial incentives to encourage healthier lifestyle choices but evidence for
      the cost-effectiveness of such interventions is lacking. Our aim was to perform a
      cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the
      use of financial incentives to increase employee physical activity levels, from a
      healthcare and employer's perspective. METHODS: Employees used a 'loyalty card'
      to objectively monitor their physical activity at work over 12 weeks. The
      Incentive Group (n=199) collected points and received rewards for minutes of
      physical activity completed. The No Incentive Group (n=207) self-monitored their
      physical activity only. Quality of life (QOL) and absenteeism were assessed at
      baseline and 6 months follow-up. QOL scores were also converted into productivity
      estimates using a validated algorithm. The additional costs of the Incentive
      Group were divided by the additional quality adjusted life years (QALYs) or
      productivity gained to calculate incremental cost effectiveness ratios (ICERs).
      Cost-effectiveness acceptability curves (CEACs) and population expected value of
      perfect information (EVPI) was used to characterize and value the uncertainty in
      our estimates. RESULTS: The Incentive Group performed more physical activity over
      12 weeks and by 6 months had achieved greater gains in QOL and productivity,
      although these mean differences were not statistically significant. The ICERs
      were L2,900/QALY and L2,700 per percentage increase in overall employee
      productivity. Whilst the confidence intervals surrounding these ICERs were wide,
      CEACs showed a high chance of the intervention being cost-effective at low
      willingness-to-pay (WTP) thresholds. CONCLUSIONS: The Physical Activity Loyalty
      card (PAL) scheme is potentially cost-effective from both a healthcare and
      employer's perspective but further research is warranted to reduce uncertainty in
      our results. It is based on a sustainable "business model" which should become
      more cost-effective as it is delivered to more participants and can be adapted to
      suit other health behaviors and settings. This comes at a time when both UK and
      US governments are encouraging business involvement in tackling public health
      challenges.

PMID- 24112296
TI  - Direct ultrasound localisation for pleural aspiration: translating evidence into
      action.
AB  - BACKGROUND: There is strong evidence that direct ultrasound localisation for
      pleural aspiration reduces complications, but this practice is not universal in
      Australia and New Zealand. AIMS: To describe the current utilisation and
      logistical barriers to the use of direct ultrasound localisation for pleural
      aspiration by respiratory physicians from Australia and New Zealand, and to
      determine the cost benefits of procuring equipment and training resources in
      chest ultrasound. METHODS: We surveyed all adult respiratory physician members of
      the Thoracic Society of Australia and New Zealand regarding their use of direct
      ultrasound localisation for pleural aspiration. We performed a cost-benefit
      analysis for acquiring bedside ultrasound equipment and estimated the capacity of
      available ultrasound training. RESULTS: One hundred and forty-six of 275
      respiratory physicians responded (53% response). One-third (33.6%) of respondents
      do not undertake direct ultrasound localisation. Lack of training/expertise
      (44.6%) and lack of access to ultrasound equipment (41%) were the most frequently
      reported barriers to performing direct ultrasound localisation. An average delay
      of 2 or more days to obtain an ultrasound performed in radiology was reported in
      42.7% of respondents. Decision-tree analysis demonstrated that clinician
      performed direct ultrasound localisation for pleural aspiration is cost
      beneficial, with recovery of initial capital expenditure within 6 months.
      Ultrasound training infrastructure is already available to up-skill all
      respiratory physicians within 2 years and is cost-neutral. CONCLUSION: Many
      respiratory physicians have not adopted direct ultrasound localisation for
      pleural aspiration because they lack equipment and expertise. However, purchase
      of ultrasound equipment is cost-beneficial, and there is already sufficient
      capacity to deliver accredited ultrasound training through existing services.

PMID- 24112297
TI  - Microdialysis as a tool for drug quantification in the bronchioles of
      anaesthetized pigs.
AB  - Target site drug determinations are crucial for optimizing treatment of
      infectious diseases. There is limited knowledge of antibiotic drug penetration
      into the pulmonary epithelial lining fluid (PELF) and a lack of easily performed
      methods for continuous drug sampling hereof. The aim of this study was to develop
      a readily accessible microdialysis (MD) method for antibiotic drug quantification
      in PELF of pigs. The fluoroquinolone danofloxacin was administered to
      anaesthetized pigs allocated to three groups: intravenous injection, intravenous
      infusion and intramuscular injection. MD probes were guided through a
      tracheostomy into the distal bronchioles using an insertion tube. Intravenously
      administered inulin served as a marker of extracellular fluid contamination of
      PELF. Concentrations of free drug in MD fractions were compared to total and non
      protein-bound drug concentrations in plasma. Rising and declining danofloxacin
      plasma concentrations were rapidly reflected in PELF, suggesting an efficient
      drug transport across the blood bronchial barrier. The AUC FREE DRUG PELF /AUC
      FREE DRUG PLASMA ratio was 1.8 (S.D. 0.4, 95% CL 1.4-2.3). Although the probes
      were placed without fiberscopic or other special equipment, the danofloxacin
      concentrations in PELF were consistent within the different administration
      groups. The described MD method for drug quantification in PELF is easily
      accessible and provides repeatable results. However, trace amount of inulin was
      detected in the MD fractions, suggesting a local tissue reaction induced by the
      MD membrane. The significance of this finding needs to be clarified in future
      studies. 

PMID- 24112298
TI  - Phagocytic microglial phenotype induced by glibenclamide improves functional
      recovery but worsens hyperalgesia after spinal cord injury in adult rats.
AB  - Microglial cell plays a crucial role in the development and establishment of
      chronic neuropathic pain after spinal cord injuries. As neuropathic pain is
      refractory to many treatments and some drugs only present partial efficacy, it is
      essential to study new targets and mechanisms to ameliorate pain signs. For this
      reason we have used glibenclamide (GB), a blocker of KATP channels that are over
      expressed in microglia under activation conditions. GB has already been used to
      trigger the early scavenger activity of microglia, so we administer it to promote
      a better removal of dead cells and myelin debris and support the microglia
      neuroprotective phenotype. Our results indicate that a single dose of GB (1 MUg)
      injected after spinal cord injury is sufficient to promote long-lasting
      functional improvements in locomotion and coordination. Nevertheless, the Randall
      Selitto test measurements indicate that these improvements are accompanied by
      enhanced mechanical hyperalgesia. In vitro results indicate that GB may influence
      microglial phagocytosis and therefore this action may be at the basis of the
      results obtained in vivo. 

PMID- 24112299
TI  - 'Are we allowed to disclose?': a healthcare team's experiences of talking with
      children and adolescents about their HIV status.
AB  - BACKGROUND: Talking with a child about their HIV status is a complex, emotionally
      laden and difficult task for caregivers and healthcare providers. Disclosure is
      an important process which may have psychosocial and health benefits. Despite
      existing guidelines and materials, disclosure does not always happen for various
      reasons. OBJECTIVE: This qualitative study explored a healthcare team's
      perspectives and experiences about disclosure practices. METHODS: Three focus
      groups were conducted with a total of 23 healthcare providers at a paediatric
      clinic in South Africa. The data were analysed using principles of thematic
      analysis. RESULTS: Results confirm the complexity of the disclosure process and
      highlight confusion, hesitancy and ethical dilemmas regarding disclosure
      practices. Tensions were noted within the team which seem linked to professional
      hierarchies. Counsellors and nurses preferred an indirect approach of encouraging
      caregivers to disclose to their children and providing psychosocial support,
      while doctors tended to become more directly involved in disclosing to children
      out of a sense of duty, legal responsibilities and knowledge of the child's
      rights. DISCUSSION AND CONCLUSIONS: This study demonstrates how the complexities
      of disclosure with children and adolescents bring about additional challenges for
      healthcare teams. The legal and ethical implications as well as the roles and
      responsibilities of healthcare providers with disclosure remain unclear. Several
      recommendations for practice and policy emerge from this study, related
      particularly to the need for clarification of disclosure guidelines and legal
      implications. Implications for the healthcare team are also discussed.

PMID- 24112300
TI  - Job satisfaction and work related variables in Chinese cardiac critical care
      nurses.
AB  - AIM: To explore critical care nurses' views of their job satisfaction and the
      relationship with job burnout, practice environment, coping style, social
      support, intention to stay in current employment and other work-related
      variables. BACKGROUND: Nurse shortage is a global issue, especially in critical
      care. Job satisfaction is the most frequently cited factor linked to nurses'
      turnover. METHOD: A convenience sample of cardiac critical care nurses (n = 215;
      97.7% response rate) from 12 large general hospitals in Shanghai was surveyed
      from December 2010 to March 2011. RESULT: Over half of the sample reported
      satisfaction with their jobs. Nurses with 10-20 years of professional experience
      and those who had taken all their holiday entitlement reported higher levels of
      job satisfaction. The independent variables of practice environment, intention to
      stay, emotional exhaustion, personal accomplishment and positive coping style
      explained about 55% of the variance in job satisfaction. CONCLUSION: Chinese
      cardiac critical care nurses' job satisfaction was related to work related
      variables, which are amenable to managerial action. IMPLICATIONS FOR NURSING
      MANAGEMENT: Our findings highlight the imperative of improving intrinsic and
      extrinsic rewards, together with the flexibility of work schedules to promote job
      satisfaction and staff retention. A clinical ladder system is needed to provide
      promotion opportunities for Chinese nurses.

PMID- 24112302
TI  - Physiological relaxation induced by horticultural activity: transplanting work
      using flowering plants.
AB  - BACKGROUND: Despite increasing attention and a growing volume of research data,
      little physiological evidence is available on the benefits of horticultural
      activity and the different effects on individuals. Therefore, the aim of the
      present study was to investigate the physiological effects of horticultural
      activity and to examine how differences in personality alter these effects.
      RESULTS: The effects of transplanting real flowers (horticultural activity) and
      handling artificial flowers (control activity) on human physiological activity
      were compared. On the first day, eight participants engaged in horticultural
      activity and another eight in the control activity. On the second day,
      participants switched roles. Participants' physiological conditions during each
      activity were assessed by measuring the heart rate and heart rate variability
      (HRV). Psychological responses, which were measured using a semantic differential
      rating scale, showed that the horticultural activity promoted comfortable,
      soothed, and natural feelings, compared to the control activity. Analysis of
      physiological responses using two-way repeated measures analysis of variance
      (ANOVA) revealed that sympathetic nervous activity significantly decreased in the
      late time period (11 to 15 minutes) of horticultural activity only in the type A
      group. CONCLUSIONS: This study supports the fact that the horticultural activity
      can enhance psychological and physiological relaxation effects, although these
      physiological effects can differ among individuals with different personalities.

PMID- 24112301
TI  - Myosin phosphatase isoforms as determinants of smooth muscle contractile function
      and calcium sensitivity of force production.
AB  - The dephosphorylation of myosin by the MP causes smooth muscle relaxation. MP is
      also a key target of signals that regulate vascular tone and thus blood flow and
      pressure. Here, we review studies from the past two decades that support the
      hypothesis that the regulated expression of MP subunits is a critical determinant
      of smooth muscle responses to constrictor and dilator signals. In particular, the
      highly regulated splicing of the regulatory subunit Mypt1 Exon 24 is proposed to
      tune sensitivity to NO/cGMP-mediated relaxation. The regulated transcription of
      the MP inhibitory subunit CPI-17 is proposed to determine sensitivity to agonist
      mediated constriction. The expression of these subunits is specific in the
      microcirculation and varies in developmental and disease contexts. To date, the
      relationship between MP subunit expression and vascular function in these
      different contexts is correlative; confirmation of the hypothesis will require
      the generation of genetically engineered mice to test the role of MP subunits and
      their isoforms in the specificity of vascular smooth muscle responses to
      constrictor and dilator signals. 

PMID- 24112303
TI  - Third-wave strategies for emotion regulation in early psychosis: a pilot study.
AB  - AIM: Emerging evidence supports the priority of integrating emotion regulation
      strategies in cognitive behaviour therapy for early psychosis, which is a period
      of intense distress. Therefore, we developed a new treatment for emotional
      regulation combining third-wave strategies, namely compassion, acceptance, and
      mindfulness (CAM) for individuals with early psychosis. The purpose of this study
      was to examine the acceptability, feasibility and potential clinical utility of
      CAM. METHOD: A non-randomized, non-controlled prospective follow-up study was
      conducted. Outpatients from the First Psychotic Episode Clinic in Montreal were
      offered CAM, which consisted of 8-week 60-75 min weekly group sessions. Measures
      of adherence to medication, symptoms, emotional regulation, distress, insight,
      social functioning and mindfulness were administered at baseline, post-treatment
      and at 3-month follow up. A short feedback interview was also conducted after the
      treatment. RESULTS: Of the 17 individuals who started CAM, 12 (70.6%) completed
      the therapy. Average class attendance was 77%. Post-treatment feedback indicated
      that participants found the intervention acceptable and helpful. Quantitative
      results suggest the intervention was feasible and associated with a large
      increase in emotional self-regulation, a decrease in psychological symptoms,
      especially anxiety, depression, and somatic concerns, and improvements in self
      care. CONCLUSION: Overall results support the acceptability, feasibility and
      potential clinical utility of the new developed treatment. A significant increase
      in emotional self-regulation and a decrease in affective symptoms were found. No
      significant changes were observed on measures of mindfulness, insight, distress
      and social functioning. Controlled research is warranted to validate the
      effectiveness of the new treatment.

PMID- 24112305
TI  - Inpatient costs, mortality and 30-day re-admission in patients with central-line
      associated bloodstream infections.
AB  - Previous work has suggested that central-line-associated bloodstream infection
      (CLABSI) is associated with increased costs and risk of mortality; however, no
      studies have looked at both total and variable costs, and information on outcomes
      outside of the intensive-care unit (ICU) is sparse. The aim of this study was to
      determine the excess in-hospital mortality and costs attributable to CLABSI in
      ICU and non-ICU patients. We conducted a retrospective cohort and cost-of-illness
      study from the hospital perspective of 398 patients at a tertiary-care academic
      medical centre from 1 January 2008 to 31 December 2010. All CLABSI patients and a
      simple random sample drawn from a list of all central lines inserted during the
      study period were included. Generalized linear models with log link and gamma
      distribution were used to model costs as a function of CLABSI and important
      covariates. Costs were adjusted to 2010 US dollars by use of the personal
      consumption expenditures for medical care index. We used multivariable logistic
      regression to identify independent predictors of in-hospital mortality. Among
      both ICU and non-ICU patients, adjusted variable costs for patients with CLABSI
      were c. $32 000 (2010 US dollars) higher on average than for patients without
      CLABSI. After we controlled for severity of illness and other healthcare
      associated infections, CLABSI was associated with a 2.27-fold (95% CI 1.15-4.46)
      increased risk of mortality. Other healthcare-associated infections were also
      significantly associated with greater costs and mortality. Overall, CLABSI was
      associated with significantly higher adjusted in-hospital mortality and total and
      variable costs than those for patients without CLABSI.

PMID- 24112304
TI  - Optimising the accuracy of blood pressure monitoring in chronic kidney disease:
      the utility of BpTRU.
AB  - BACKGROUND: Accurate blood pressure monitoring is critical for the management of
      chronic kidney disease, but changes in management in secondary care clinics may
      be based on a single blood pressure reading, with a subsequent lack of accuracy.
      The aim of this study was to evaluate a fully automated sphygmomanometer for
      optimising the accuracy of blood pressure measurements in the setting of
      secondary care renal clinics. METHODS: Patients had routine blood pressure
      measurements with a calibrated DINAMAP PRO400 monitor in a clinical assessment
      room. Patients then underwent repeat assessment with a DINAMAP PRO400 monitor and
      BpTRU device and subsequent 24 hour ambulatory blood pressure monitoring (ABPM).
      RESULTS: The BpTRU systolic (+/- SD) reading (117.3 +/- 14.1 mmHg) was
      significantly lower than the routine clinic mean systolic blood pressure (143.8
      +/- 15.5 mmHg; P < 0.001) and the repeat blood pressure taken with a DINAMAP
      PRO400 monitor in a quiet room (129.9 +/- 19.9 mmHg; P < 0.001). The routine
      clinic mean diastolic (82.4 +/- 11.2 mmHg) was significantly higher than the
      BpTRU reading (78.4 +/- 10.0 mmHg; P < 0.001). Clinic BpTRU measurements were not
      significantly different to the daytime mean or overall mean of 24 hour ABPM.
      CONCLUSIONS: In patients with CKD, routine clinic blood pressure measurements
      were significantly higher than measurements using a BpTRU machine in a quiet
      room, but there was no significant difference in this setting between BpTRU
      readings and 24 hour ABPM. Adjusting clinic protocols to utilise the most
      accurate blood pressure technique available is a simple manoeuvre that could
      deliver major improvements in clinical practice.

PMID- 24112306
TI  - The role of commitment strength in enhancing safe water consumption: mediation
      analysis of a cluster-randomized trial.
AB  - OBJECTIVES: The objectives of this study were to investigate the importance of
      commitment strength in the theory of planned behaviour (TPB) and to test whether
      behaviour change techniques (BCTs) aimed at increasing commitment strength indeed
      promote switching to arsenic-safe wells by changing commitment strength. DESIGN:
      A cluster-randomized controlled trial with four arms was conducted to compare an
      information-only intervention to information plus one, two, or three commitment
      enhancing BCTs. METHODS: Randomly selected households (N = 340) of Monoharganj,
      Bangladesh, in seven geographically separate areas, whose members were drinking
      arsenic-contaminated water at baseline and had access to arsenic-safe wells,
      participated in this trial. The areas were randomly allocated to the four
      intervention arms. Water consumption behaviour, variables of the TPB, commitment
      strength, and socio-demographic characteristics were assessed at baseline and at
      3-month follow-up by structured face-to-face interviews. Mediation analysis was
      used to investigate the mechanisms of behaviour change. RESULTS: Changes in
      commitment strength significantly increased the explanatory power of the TPB to
      predict well-switching. Commitment-enhancing BCTs - public self-commitment,
      implementation intentions, and reminders - increased the behaviour change effects
      of information by up to 50%. Mediation analyses confirmed that the BCTs indeed
      increased well-switching by increasing commitment strength. Unexpectedly,
      however, mediation via changes in behavioural intentions was the strongest
      mechanism of the intervention effects. CONCLUSIONS: Commitment is an important
      construct to consider in water- and health-related behaviour change and may be
      for other health behaviours as well. BCTs that alter behavioural intentions and
      commitment strength proved highly effective at enhancing the behaviour change
      effects of information alone. Statement of contribution What is already known on
      this subject? Millions of people drink contaminated water even if they have
      access to safe water alternatives and despite increased awareness of the
      consequences to health. The theory of planned behaviour (TPB) and commitment
      strength are predictive of safe water consumption. The potentially commitment
      enhancing behaviour change techniques (BCTs) - reminders, implementation
      intentions, and public self-commitment - can promote health behaviours, including
      safe water consumption. What does this study add? Changes in commitment strength
      significantly added to the prediction of switching to arsenic-safe wells by the
      TPB. Information-plus-BCTs aimed at increasing commitment strength led to >50%
      more well-switching than information alone. Behaviour change effects of the BCTs
      were mediated by changes in commitment strength and behavioural intentions.

PMID- 24112307
TI  - Nursing diagnoses among kidney transplant recipients: evidence from clinical
      practice.
AB  - PURPOSE: Identify the nursing diagnoses applied to kidney transplant recipients
      at a Brazilian hospital. METHODS: Cross-sectional study with a study sample of
      165 patients who underwent transplant from January 2007 through January 2009.
      CONCLUSIONS: Six nursing diagnoses were most prevalent among kidney transplant
      recipients in the postoperative period: risk for infection, impaired urinary
      elimination, ineffective protection, bathing self-care deficit, impaired tissue
      integrity, and acute pain. IMPLICATIONS FOR NURSING PRACTICE: Provide information
      on the priority health needs of these patients and reinforced the importance of
      the proper development of the nursing care plan.

PMID- 24112309
TI  - Oxidative stress in neonatology: a review.
AB  - Free radicals are highly reactive oxidizing agents containing one or more
      unpaired electrons. Both in human and veterinary neonathology, it is generally
      accepted that oxidative stress functions as an important catalysator of neonatal
      disease. Soon after birth, many sudden physiological and environmental conditions
      make the newborn vulnerable for the negative effects of oxidative stress, which
      potentially can impair neonatal vitality. As a clinician, it is important to have
      in depth knowledge about factors affecting maternal/neonatal oxidative status and
      the cascades of events that enrol when the neonate is subjected to oxidative
      stress. This report aims at providing clinicians with an up-to-date review about
      oxidative stress in neonates across animal species. It will be emphasized which
      handlings and treatments that are applied during neonatal care or resuscitation
      can actually impose oxidative stress upon the neonate. Views and opinions about
      maternal and/or neonatal antioxydative therapy will be shared. 

PMID- 24112308
TI  - Collembola, the biological species concept and the underestimation of global
      species richness.
AB  - Despite its ancient origin, global distribution and abundance in nearly all
      habitats, the class Collembola is comprised of only 8000 described species and is
      estimated to number no more than 50,000. Many morphologically defined species
      have broad geographical ranges that span continents, and recent molecular work
      has revealed high genetic diversity within species. However, the evolutionary
      significance of this genetic diversity is unknown. In this study, we sample five
      morphological species of the globally distributed genus Lepidocyrtus from 14
      Panamanian sampling sites to characterize genetic diversity and test
      morphospecies against the biological species concept. Mitochondrial and nuclear
      DNA sequence data were analysed and a total of 58 molecular lineages revealed.
      Deep lineage diversification was recovered, with 30 molecular lineages estimated
      to have established more than 10 million years ago, and the origin almost all
      contemporary lineages preceding the onset of the Pleistocene (~2 Mya). Thirty
      four lineages were sampled in sympatry revealing unambiguous cosegregation of
      mitochondrial and nuclear DNA sequence variation, consistent with biological
      species. Species richness within the class Collembola and the geographical
      structure of this diversity are substantially misrepresented components of
      terrestrial animal biodiversity. We speculate that global species richness of
      Collembola could be at least an order of magnitude greater than a previous
      estimate of 50,000 species.

PMID- 24112310
TI  - Barrow-in-Furness: a large community legionellosis outbreak in the UK.
AB  - A community outbreak of legionellosis occurred in Barrow-in-Furness, Cumbria,
      during July and August 2002. A descriptive study and active case-finding were
      instigated and all known wet cooling systems and other potential sources were
      investigated. Genotypic and phenotypic analysis, and amplified fragment length
      polymorphism of clinical human and environmental isolates confirmed the air
      conditioning unit of a council-owned arts and leisure centre to be the source of
      infection. Subsequent sequence-based typing confirmed this link. One hundred and
      seventy-nine cases, including seven deaths [case fatality rate (CFR) 3.9%] were
      attributed to the outbreak. Timely recognition and management of the incident
      very likely led to the low CFR compared to other outbreaks. The outbreak
      highlights the responsibility associated with managing an aerosol-producing
      system, with the potential to expose and infect a large proportion of the local
      population and the consequent legal ramifications and human cost.

PMID- 24112311
TI  - Dose adjustment guidelines for medications in patients with renal impairment: how
      consistent are drug information sources?
AB  - BACKGROUND: It is known that patients with renal disease are often administered
      inappropriate dosages of drugs. A lack of quantitative data in the available drug
      information sources and inconsistency in dosing information may augment the
      problem of dosing error. AIMS: To determine the concordance among five drug
      information sources regarding the dosing recommendations provided for drugs
      considered problematic in patients with renal impairment and to determine the
      consistency among the sources regarding the definition of renal impairment and
      categorisation of chronic kidney disease. METHODS: Five standard drug information
      sources were reviewed for 61 drugs recommended to be used with caution in renal
      impairment. Information on recommendations for dosage adjustment in renal
      impairment was extracted and analysed. Further, the definition and classification
      of renal impairment were recorded. The recommendation for each drug was coded
      into six different categories and the intersource reliability was calculated.
      RESULTS: Only slight agreement was observed among the sources (Fleiss Kappa:
      0.3). Qualitative data were not well defined, and there was a lack of consistency
      in quantitative values. Some drugs marked as contraindicated in one source were
      not mentioned as such in others. Also, drugs considered as not requiring dosage
      adjustment in one source had explicit recommendations in other sources. The
      definition and classification of renal impairment differed among the five
      information sources. CONCLUSIONS: There should be an evidence-based approach to
      drug dosage adjustment in order to bring uniformity to the recommendations.
      Regular updating of the content of the drug information sources is also
      important.

PMID- 24112313
TI  - Using a safe taxi service to transport newborn babies home from hospital.
AB  - AIM: To evaluate an intervention to enhance parents' use of car safety seats
      (CSSs) for their newborn baby's first journey home from the hospital in a
      population not usually exposed to television, internet and mainstream printed
      media. METHODS: Parents of newborn babies who did not bring a CSS to the hospital
      before their baby was discharged were lent a CSS to use in a 'safe taxi' service.
      All taxi drivers were trained to install the CSS safely. The intervention was
      evaluated using preprogramme questionnaires and follow-up interviews 4-8 weeks
      after discharge. RESULTS: Twelve parents participated in the intervention during
      the study period (January to April 2011) and in the evaluation process. Eleven
      couples were Jewish and one was Muslim. Most (75%) reported that they had not
      previously used CSS routinely and the reason was not financial. Following the
      'safe taxi' intervention, 83% reported the use of CSS when travelling in all
      vehicles (excluding buses). On follow-up, most participants reported that the
      intervention increased their awareness and the use of CSS. CONCLUSION: The
      intervention, targeted at this specific population, was well received by the
      parents, increased awareness, changed practices and assured that more newborns
      travelled home safely in a CSS.

PMID- 24112312
TI  - Joint replacement recipients' views about health information privacy.
AB  - BACKGROUND: Researchers are concerned about the possibility of restricted access
      to data as a result of specific consent requirements in privacy legislation,
      potentially resulting in smaller samples and a lack of representativeness which
      could bias results. In addition, there is uncertainty about what influences
      individuals to give consent for the use of their personal health information.
      OBJECTIVE: To measure joint replacement recipients' health information privacy
      views and to assess potential predictors of these views. DESIGN: Cross-sectional
      survey. SETTING AND PARTICIPANTS: Potential joint replacement recipients from two
      teaching hospitals in London, Ontario, Canada. MAIN VARIABLES: Age, gender,
      education, employment status, anticipated joint replacement, and expectations for
      surgery. MAIN OUTCOME MEASURES: Privacy concerns as measured by the Concern
      Scale. RESULTS: The response rate was 182/253 or 72%. The mean Concern score was
      143.9/235.0 for the total sample (range = 82-216). Women had higher levels of
      privacy concerns than men on slightly over half of the individual questionnaire
      items. In women, surgical joint, age and employment explained 15% of the variance
      in concerns about personal health information privacy (P = 0.001). The model
      explained 6% of the variance in concerns in men (P = 0.138) and was not
      statistically significant. DISCUSSION AND CONCLUSION: This study indicates that
      demographic characteristics and health-care experiences play a role in the
      variability of health information privacy concerns. A greater understanding of
      patients' privacy views about health information could lead to a greater
      harmonization among privacy rules, research and data access, and the preferences
      of health-care consumers.

PMID- 24112314
TI  - Bilioportal fistula associated with pigtail biliary drainage tube use.

PMID- 24112315
TI  - Estimating reliable paediatric reference intervals in clinical chemistry and
      haematology.
AB  - Very few high-quality studies on paediatric reference intervals for general
      clinical chemistry and haematology analytes have been performed. Three recent
      prospective community-based projects utilising blood samples from healthy
      children in Sweden, Denmark and Canada have substantially improved the situation.
      CONCLUSION: The present review summarises current reference interval studies for
      common clinical chemistry and haematology analyses.

PMID- 24112316
TI  - Nutravigilance: principles and practices to enhance adverse event reporting in
      the dietary supplement and natural products industry.
AB  - Nutravigilance is defined as "the science and activities relating to the
      detection, assessment, understanding and prevention of adverse effects related to
      the use of a food, dietary supplement, or medical food". The nutravigilance
      approach is derived from well-defined principles of pharmacovigilance in the drug
      and biologics industries, which have been developed and refined over a number of
      years through expert recommendations. While the primary purpose of nutravigilance
      is to protect customer/patient safety, it also serves to reduce product liability
      risks for manufacturers and marketing agents of such products. Compliance with
      the current FDA adverse event reporting requirements is suboptimal, and FDA
      oversight and enforcement activities have recently increased. In order to better
      protect customer and product safety, dietary supplement manufacturers must
      significantly change their current approach, and demonstrate a proactive,
      systematic, risk-based, scientific approach to product safety, similar to one
      utilized successfully in the pharmaceutical industry. While this article focuses
      on FDA regulations, the principles are widely relevant to the supplement industry
      in the rest of the world.

PMID- 24112317
TI  - Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus
      statement (small animal).
AB  - This report offers a consensus opinion on the diagnosis of spontaneous canine
      hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is
      based on the history and physical examination. Endocrine tests should be
      performed only when clinical signs consistent with HAC are present. None of the
      biochemical screening or differentiating tests for hyperadrenocorticism are
      perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has
      heightened over time. Thus, case presentation is more subtle. Due to the changes
      in manifestations as well as test technology the Panel believes that references
      ranges should be reestablished. The role of cortisol precursors and sex hormones
      in causing a syndrome of occult hyperadrenocorticism remains unclear. 

PMID- 24112319
TI  - Moral sensitivity and critical thinking disposition of nursing students in Korea.
AB  - This study aimed to examine the level of moral sensitivity and critical thinking
      disposition among baccalaureate nursing students in Korea. A convenience sample
      of 142 undergraduate nursing students was surveyed on moral sensitivity using the
      Korean version of the Moral Sensitivity Questionnaire (K-MSQ) and on critical
      thinking disposition using the Critical Thinking Disposition Questionnaire
      (CTDQ). Data were collected from June 2009 to July 2010. Mean score was 2.83 out
      of 7 on the K-MSQ (relatively low) and 3.70 out of 5 on the CTDQ (relatively
      high), indicating the need for nursing educators to continue to develop and
      incorporate strategies that enhance moral sensitivity into ethics courses in
      undergraduate nursing programs in Korea. Nursing students who regarded nursing as
      a lifelong career exhibited stronger critical thinking disposition than did
      students who considered nursing to be a temporary or premarital job. Moral
      sensitivity should be further emphasized in nursing ethics courses in
      undergraduate nursing programs in Korea. 

PMID- 24112318
TI  - Relationship between sclerostin and cardiovascular calcification in hemodialysis
      patients: a cross-sectional study.
AB  - BACKGROUND: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity
      and bone turnover. Here, we assessed the potential association of sclerostin with
      the development of coronary artery (CAC) and aortic valve calcifications (AVC) in
      haemodialysis (HD) patients. METHODS: We conducted a cross-sectional multi-slice
      computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 +/-
      14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as
      well as serum sclerostin (ELISA) regarding their association to the presence of
      calcification. Fifty-four adults without relevant renal disease served as
      controls for serum sclerostin levels. Additionally, sclerostin expression in
      explanted aortic valves from 15 dialysis patients was analysed ex vivo by
      immunohistochemistry and mRNA quantification (Qt-RT-PCR). RESULTS: CAC (Agatston
      score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient
      group, respectively. Serum sclerostin levels (1.53 +/- 0.81 vs 0.76 +/- 0.31
      ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more
      so in HD patients with AVC versus those without AVC (1.78 +/- 0.84 vs 1.35 +/-
      0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed
      significant associations with higher serum sclerostin. Ex vivo analysis of
      uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression
      very close to calcified regions (no sclerostin staining in non-calcified valves).
      Correspondingly, we observed a highly significant upregulation of sclerostin mRNA
      in calcified valves compared to non-calcified control valves. CONCLUSION: We
      found a strong association of sclerostin with calcifying aortic heart valve
      disease in haemodialysis patients. Sclerostin is locally produced in aortic valve
      tissue adjacent to areas of calcification.

PMID- 24112320
TI  - Descriptive epidemiology of chronic liver disease in northeastern Italy: an
      analysis of multiple causes of death.
AB  - BACKGROUND: The analysis of multiple causes of death data has been applied in the
      United States to examine the population burden of chronic liver disease (CLD) and
      to assess time trends of alcohol-related and hepatitis C virus (HCV)-related CLD
      mortality. The aim of this study was to assess the mortality for CLD by etiology
      in the Veneto Region (northeastern Italy). METHODS: Using the 2008-2010 regional
      archive of mortality, all causes registered on death certificates were extracted
      and different descriptive epidemiological measures were computed for HCV-related,
      alcohol-related, and overall CLD-related mortality. RESULTS: The crude mortality
      rate of all CLD was close to 40 per 100,000 residents. In middle ages (35 to 74
      years) CLD was mentioned in about 10% and 6% of all deaths in males and females,
      respectively. Etiology was unspecified in about half of CLD deaths. In females
      and males, respectively, HCV was mentioned in 44% and 21% and alcohol in 11% and
      26% of overall CLD deaths. A bimodal distribution with age was observed for HCV
      related proportional mortality among females, reflecting the available
      seroprevalence data. CONCLUSIONS: Multiple causes of death analyses can provide
      useful insights into the burden of CLD mortality according to etiology among
      different population subgroups.

PMID- 24112321
TI  - An international survey of speciality training in oral and maxillofacial
      pathology.
AB  - BACKGROUND: Speciality training in oral and maxillofacial pathology (OMFP) across
      the world would be aided by guidance on a generic curriculum and training
      programme that all countries could use as a template. In order to facilitate
      this, we require an understanding of the various forms which OMFP training takes
      across the world. METHODS: We sent a questionnaire to OMF pathologists in the 42
      countries represented in the IAOP membership, via their Regional Councillor. The
      questionnaire included detailed demographics, entry requirements, specialty
      training program and facilities/resources. RESULTS: Replies were received from
      22/42 countries (52%). OMFP is a dental/dental and medical speciality in 72%, and
      in 92% of those, this is recognised by a licensing board. Training was undertaken
      in an academic environment in 85% (with many offering a further academic
      qualification) and the median length of training was 4 years. General/anatomical
      pathology training is mandated in 85% of programs and a common core of general
      sub-specialities was identified. An end of training assessment was conducted in
      80% of programs with most including written, practical and oral elements.
      Training program directors and educational supervisors were in place in 12/16
      programs and, in most, Quality Assurance of training was externally monitored. In
      only one country was the number of trainees linked to workforce planning.
      CONCLUSIONS: Training in OMFP varies across the world. However, we feel there is
      sufficient commonality for the development of an agreed indicative framework on
      education and training in Oral and Maxillofacial Pathology, perhaps under the
      auspices of the IAOP.

PMID- 24112322
TI  - Determination of ethyl glucuronide in human hair by hydrophilic interaction
      liquid chromatography-tandem mass spectrometry.
AB  - Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been utilized
      as a marker for alcohol intake. This study presents development, validation and
      application of a new hydrophilic interaction liquid chromatography-tandem mass
      spectrometry (HILIC-MS/MS) method for the analysis of EtG in human hair samples.
      The linearity was assessed in the range of 5-2000 pg/mg hair, with a correlation
      coefficient of >0.99. The method was selective and sensitive, with a limit of
      detection (LOD) and limit of quantitation (LOQ) of 0.05 pg/mg and 0.18 pg/mg in
      hair, respectively. Differently from the extraction procedures in the literature,
      a fast and simple liquid-liquid method was used and highest recoveries and
      cleanest extracts were obtained. The method was successfully applied to 30 human
      hair samples which were taken from those who state they consume alcohol. EtG
      concentrations in the hair samples of alcohol users participated in this study,
      ranged between 1.34 and 82.73 pg/mg. From the concentration of EtG in hair
      strands 20 of the 30 subjects can be considered regular moderate drinkers. 

PMID- 24112323
TI  - Ice pick death: a case report and discussion of the injury pattern.
AB  - Death due to ice pick injury rarely reported in forensic literature. We report
      death of a 16-year old male, who was allegedly assaulted on chest, back and thigh
      by his school-mate, with an ice pick. The accused had got the ice pick from his
      father's ice shop to attack the victim. The multiple stabs to the chest region
      had perforated the lung and penetrated the heart chambers. The victim succumbed
      to death on the way to hospital and medico-legal autopsy was conducted. The
      injuries inflicted by the ice pick are highlighted and its pattern is discussed
      in this article, owing to the peculiar nature of the wounds produced by the ice
      pick. 

PMID- 24112324
TI  - Delayed diagnosis of self-inflicted cuts - a case report.
AB  - Assessment of individuals with injuries that may have been caused by intentional
      self-harm is part of routine work of forensic physicians. We present a case of
      deliberate self-harm of a 19 years old woman who claimed she had been cut by her
      partner during a quarrel while her partner claimed that she had injured herself.
      No forensic examination was performed. The case was first reviewed several months
      after the incident by experts giving consultations for the defense (the authors)
      by that time the only documentation of injury available were scant medical
      records and photos of very low quality. This case shows the importance of
      recognizing self-inflicted injuries even when only scant documentation is
      available, by comparing the injuries described to the different accounts of the
      incident as described by the complainant and defendant. Also the importance of
      availability of access of defense lawyers to forensic medical consultations is
      stressed. 

PMID- 24112325
TI  - Ibogaine related sudden death: a case report.
AB  - Ibogaine is a naturally occurring alkaloid derived from the roots of the rain
      forest shrub Tabernanthe iboga. Deaths have occurred temporarily related to the
      use of ibogaine. However, although not licensed as therapeutic drug, and despite
      evidence that ibogaine may disturb the rhythm of the heart, this alkaloid is
      currently used as an anti-addiction drug in alternative medicine for
      detoxification purposes. We report the case of a man who died suddenly 12-24 h
      after ibogaine use for alcohol detoxification treatment. In the autopsy liver
      cirrhosis and heavy fatty infiltration was found. The concentration of ibogaine
      was 2 mg/l. The potential risks of ibogaine use, especially for persons with
      pathological medical background, are discussed. 

PMID- 24112326
TI  - Sudden death in custody due to pituitary apoplexy during long restriction in a
      sitting position: a case report and review of the literature.
AB  - Pituitary apoplexy is an uncommon clinical emergency arising from hemorrhage into
      or infarction of a pituitary adenoma. The most common presentation is sudden
      headache, visual field defects and signs of hypopituitarism. It usually occurs in
      the age group from 20 to 50 years and affects more male than female. Sudden death
      due to pituitary apoplexy without common symptoms is rarely reported. Here, we
      described a scarcely-reported case of sudden death in custody caused by pituitary
      apoplexy resulting from stress-induced hemorrhage of gonadotroph adenoma, a kind
      of pituitary adenoma, without common clinical symptoms. In this case, a 49-year
      old man was restrained in a sitting position for 4 days and died unexpectedly. At
      autopsy, external examination showed free of trauma. Destruction of bony
      structure and a circumscribed pituitary tumor were observed in sella turcica.
      Immunohistochemically, the tumor cells were particular positive for follicle
      stimulating hormone (FSH) and luteinizing hormone (LH), thus clarifying the
      presence of a pituitary gonadotroph adenoma. We provide the case description and
      a short review of pituitary apoplexy and pituitary adenoma as a rare cause of
      sudden death. 

PMID- 24112327
TI  - Future delivery of the Drug Interventions Programme: do the benefits justify the
      costs?
AB  - The Drug Interventions Programme is an initiative employed by the Home Office in
      2003 to integrate the Criminal Justice System with drug treatment services with
      the ultimate goal of reducing acquisitive crime. Drug Action Teams employ this
      scheme on a local level by providing a broad range of services for misusers in
      the community. Although much attention has been placed on societal gains, there
      is an added benefit in improving the health outcomes of those referred. Opioid
      replacement therapy decreases illicit heroin use, reduces mortality and maintains
      contact with misusers allowing for psychosocial intervention. The Drug
      Interventions Programme provides direct access to such treatment in an otherwise
      high-risk and disengaged population. Anecdotal evidence of the programme is
      positive; with improved mental and physical health in offenders and a reduction
      in hospital admissions. However, monitoring health outcomes in offenders is
      challenging as long-term follow-up is difficult, poor compliance is an issue and
      coercive referrals may introduce a reporting bias. Drug Action Team services are
      cost-effective due a lower consumption of health and social care and reduced
      offending levels. The Drug Interventions Programme has been successful in
      maintaining offenders in treatment and the Home Office claim its role in reducing
      crime is cost-saving. Future delivery of the initiative is at risk due to
      spending reductions, competing interests and a focus towards payment by results.
      Opposition to future implementation of the Drug Interventions Programme must be
      met with evidence for its effectiveness in order to ensure its continued
      investment. 

PMID- 24112328
TI  - Sure he's dead? Be wise.

PMID- 24112329
TI  - Guidelines on disposition of forensic psychiatric patients are urgent needed in
      China.

PMID- 24112330
TI  - Automatism and driving offences.
AB  - Automatism is a rarely used defence, but it is particularly used for driving
      offences because many are strict liability offences. Medical evidence is almost
      always crucial to argue the defence, and it is important to understand the bars
      that limit the use of automatism so that the important medical issues can be
      identified. The issue of prior fault is an important public safeguard to ensure
      that reasonable precautions are taken to prevent accidents. The total loss of
      control definition is more problematic, especially with disorders of more gradual
      onset like hypoglycaemic episodes. In these cases the alternative of 'effective
      loss of control' would be fairer. This article explores several cases, how the
      criteria were applied to each, and the types of medical assessment required. 

PMID- 24112331
TI  - Unconsciousness and sedation as precipitating factors of diabetic ketoacidosis.
AB  - The aim of this study was to identify medico-legal situations characterized by
      increased vitreous glucose concentrations, potentially lethal blood 3
      hydroxybutyrate levels and conditions that could either incapacitate or lead to
      death on their own. The above was investigated in order to verify whether
      prolonged states of unconsciousness may play a role in precipitating diabetic
      ketoacidosis. Six groups of medico-legal situations (corresponding to 206 autopsy
      cases) were identified. Among these, three cases were characterized by
      pathologically increased vitreous glucose and blood 3-hydroxybutyrate levels. In
      one case diabetic ketoacidosis coexisted with underlying features that might have
      potentially incapacitated or lead to death on their own, whereas in two cases it
      corresponded with potentially lethal or lethal drug concentrations. The results
      of this study highlight the usefulness of systematically performing biochemistry
      in order to identify diabetic ketoacidosis-related deaths, even when autopsy and
      toxicology results provide apparently conclusive findings. 

PMID- 24112332
TI  - Men victim of sexual assault of concern into the first Emergency Medical Unit for
      Victims of Assaults in France.
AB  - Although it accounts for only a small part of activity in the field of
      victimology, the provision of support for male victims of sexual assault is
      regularly discussed in the literature. Authors, English-speaking for the most
      part, all agree that this phenomenon has been largely underestimated, owing to
      the stigmatization victims suffer after the facts have been disclosed. The same
      authors agree that this type of assault is far from being inconsequential, from
      both a physical and a psychological perspective. The following retrospective and
      descriptive study, conducted at the Bordeaux CHU (Bordeaux University Hospital),
      aims to draw a comparison between the distinctive characteristics of male sexual
      assault victims treated at the CAUVA (Centre d'Accueil en Urgence des Victimes
      d'Agression - Emergency Medical Unit for Victims of Assaults) on the one hand,
      and, on the other hand, those identified in the existing scientific literature.
      The victims are predominantly young men, unconnected with their attackers, and
      more often than not the attacks take place on the public highway. Forensic
      treatment is provided within the seven days following the assault, which raises
      the question of the assessment of infection risks, including HIV transmission.
      Most of the time, the victims will not undergo a full psychological appraisal,
      though authors are unanimous that such assaults do indeed have heavy
      repercussions. Improving our services for such victims will require suitable
      training for staff, covering initial reception, general assessment and the
      drafting of the forensic medical report, as well as encouragement to lodge a
      complaint. This process should give priority to multidisciplinary centers,
      especially dedicated to shelter-providing, information, counseling and victim
      support. This will also entail information and awareness campaigns for the
      general population, and the homosexual community in particular. Finally, we
      should not be afraid to envisage an investigation into this subject at an
      international level. 

PMID- 24112333
TI  - Toxicology findings in suicides: concentrations of ethanol and other drugs in
      femoral blood in victims of hanging and poisoning in relation to age and gender
      of the deceased.
AB  - Over-consumption of alcohol and/or abuse of other drugs are closely linked to
      attempted or completed suicides. In this retrospective 10-year study (2001-2010),
      we compared the toxicology findings in hanging suicides (n = 4551) with drug
      poisoning (intoxication) suicides (n = 2468). The mean age of hanging deaths was
      49 +/- 19 y (+/-SD) and 80% were male, compared with a mean age of 52 +/- 17 y
      and 47% males for the intoxication deaths. Poly-drug use was more common in
      poisoning suicides with an average of 3.6 drugs/case compared with 1.8 drugs/case
      in hangings. Moreover, 31% of hangings were negative for alcohol and/or drugs.
      Alcohol was detected (>0.20 g/L) in femoral blood in 30% of hanging suicides
      (mean 1.39 g/L) and 36% of drug poisonings (mean 1.39 g/L). The median BACs did
      not depend on the person's age or gender (p > 0.05). Ethanol, paracetamol,
      citalopram, diazepam, propiomazine, alimemazine and zopiclone were amongst the
      top-ten drugs detected in both methods of suicide. With the exception of ethanol,
      the concentrations of drugs in blood were considerably higher in the poisoning
      deaths, as might be expected. Regardless of the method of suicide,
      antidepressants and/or antipsychotics were common findings, which could implicate
      mental health as a significant suicide risk factor. 

PMID- 24112334
TI  - Coronial autopsy in a rural setting.
AB  - OBJECTIVES: To determine the precise nature of the non-homicide coronial autopsy.
      DESIGN AND SETTING: Retrospective analysis of coronial autopsies between 2005 and
      2011 in a rural setting on the Mid North Coast of New South Wales. RESULTS: A
      total of 1446 autopsies were performed during the 7 year study period. There were
      1428 (98.75%) coronial and 18 (1.25%) hospital autopsies. Death in the coronial
      cases was attributed to natural causes in 829 (58%) of the cases, accidental
      causes in 321 (22.5%) of the cases, suicide in 244 (17%) of the cases and no
      apparent cause (indeterminate) in 34 (2.5%) of the cases. Acute myocardial
      ischaemia constituted 66.7% of the natural causes. Road traffic and other
      motorised vehicle-related accidents were responsible for 60.7% of deaths in the
      accidental group. The 2 main types of death in the suicide group were hanging
      (36.5%) and drug overdose (31.5%). In 34 deaths, the cause remained unclear,
      however, because of lack of suspicious circumstances and negative histology and
      toxicology, they were presumed to be due to natural causes. CONCLUSIONS: The
      hospital autopsy has almost completely disappeared. On the other hand, coronial
      autopsies are on the rise. General Practitioners appear reluctant to issue death
      certificates in certain situations where there are no suspicious circumstances
      and the Coroners feel obliged to ask for autopsies. Currently, there is a severe
      shortage of pathologist and the additional coronial works adds to the burden on
      those pathologists who engage in such work. The coronial system needs to think
      about the role of the autopsy in these circumstances. Furthermore, additional
      resources from the various stakeholders are required for the increasing
      educational role of the coronial autopsy in undergraduate and postgraduate
      teaching.

PMID- 24112335
TI  - Cardiac laceration without any external chest injury in an otherwise healthy
      myocardium - a case series.
AB  - The heart is relatively well protected within the thoracic cavity from all the
      sides. Thus it is rather uncommon to find a cardiac laceration in cases of blunt
      trauma to the chest and that too when there is no evident injury to the chest
      wall. Several cases with history of death following blunt trauma were autopsied
      by us in recent months. Out of them, 3 cases that did not exhibit any external
      chest injury revealed hemopericardium following rupture of a cardiac chamber. The
      volume and suddenness of appearance of the hemopericardium were sufficient to
      cause tamponade. These case reports underline the importance of a systematic and
      complete autopsy in all cases of blunt trauma deaths even though they may be
      having no external injury. They also highlight that myocardial injury must be
      ruled out in every living patient presenting with blunt chest trauma even in the
      absence of an external sign. 

PMID- 24112336
TI  - Estimation of sex from mastoid triangle - a craniometric analysis.
AB  - Estimation of sex is an important step in the evaluation of unknown human
      remains. Human skulls are shown to exhibit sexual dimorphism. The objective of
      the present study was to assess the mastoid region in sexing of unknown skulls.
      The present study was conducted on 118 (69 males and 49 females) dry skulls in a
      Medical College at India. The dimensions, area, perimeter, and the angles of the
      mastoid triangle were analysed for their utility in sex estimation. Non
      parametric Mann-Whitney U test was employed to study the sex differences in the
      different variables. Receiver Operating Characteristic (ROC) curve was used for
      testing the overall ability of the variables in sex estimation. The present
      investigation confirms the low accuracy of the mastoid region in sex estimation.
      The study concludes that the mastoid triangle is a poor indicator of sex, and of
      limited significance without population reference. 

PMID- 24112337
TI  - Two new oro-cervical radiographic indexes for chronological age estimation: a
      pilot study on an Italian population.
AB  - Chronological age (CA) plays a fundamental role in forensic dentistry (i.e.
      personal identification and evaluation of imputability). Even though several
      studies outlined the association between biological and chronological age, there
      is still great variability in the estimates. The aim of this study was to
      determine the possible correlation between biological and CA age through the use
      of two new radiographic indexes (Oro-Cervical Radiographic Simplified Score -
      OCRSS and Oro-Cervical Radiographic Simplified Score Without Wisdom Teeth -
      OCRSSWWT) that are based on the oro-cervical area. Sixty Italian Caucasian
      individuals were divided into 3 groups according to their CA: Group 1: CAG 1 = 8
      14 yr; Group 2: CAG 2 = 14-18 yr; Group 3: CAG 3 = 18-25 yr; panorexes and
      standardised cephalograms were evaluated according Demirjian's Method for dental
      age calculation (DM), Cervical Vertebral Maturation method for skeletal age
      calculation (CVMS) and Third Molar Development for age estimation (TMD). The
      stages of each method were simplified in order to generate OCRSS, which
      summarized the simplified scores of the three methods, and OCRSSWWT, which
      summarized the simplified DM and CVMS scores. There was a significant correlation
      between OCRSS and CAGs (Slope = 0.954, p < 0.001, R-squared = 0.79) and between
      OCRSSWWT and CAGs (Slope = 0.863, p < 0.001, R-squared = 0.776). Even though the
      indexes, especially OCRSS, appear to be highly reliable, growth variability among
      individuals can deeply influence the anatomical changes from childhood to
      adulthood. A multi-disciplinary approach that considers many different biomarkers
      could help make radiological age determination more reliable when it is used to
      predict CA. 

PMID- 24112338
TI  - Post-traumatic dissection of the internal carotid artery associated with
      ipsilateral facial nerve paralysis: diagnostic and forensic issues.
AB  - Traumatic internal carotid artery dissection may result from a direct blow to
      anterolateral aspect of the neck, or an extreme extension and rotation of the
      neck. Traumas involved are variable ranging from high speed motor vehicle
      accident to trivial traumas. The most frequent presentations of carotid artery
      dissection are stroke, Horner syndrome, and paralysis of a cranial nerve. Time of
      ischemic signs onset is very variable too, diverging from immediate to several
      months delay. We report the case of a 60-year-old woman, who was assaulted by a
      young man. Immediately, she complained of headache and posterior cervical pain.
      Three months later she developed a left hemifacial paralysis. MRI and MRA showed
      a dissection of the left internal carotid artery. The causal relationship between
      the trauma and the carotid artery dissection as well as forensic issues are
      discussed. 

PMID- 24112339
TI  - Saccadic eye movements after low-dose oral alcohol exposure.
AB  - OBJECTIVES: The influence of low-dose alcohol intake on reflexive visually guided
      saccades was investigated. METHODS: 40 healthy human subjects were orally given
      alcohol resulting in low-dose alcohol concentration (less than 0.80/00) blood
      alcohol concentration. Before and after exposure, horizontal saccadic eye
      movements were recorded at several points in time. The recordings were evaluated
      with regard to accuracy of the eye movements, latency, the peak eye velocity and
      the time constant that characterizes the main sequence. The results were compared
      to recordings from a reference group. RESULTS: It was found that the saccadic eye
      movement was clearly altered by low-dose alcohol intake. However, its
      characteristics were not unambiguously pathological when compared to the
      reference group, even though the subjects reported a moderate to strong effect of
      alcohol and there were clear signs of inebriation. CONCLUSIONS: The findings
      render the evaluation of saccades unsuitable as a simple test for the detection
      of low-dose alcohol intake.

PMID- 24112340
TI  - A comparison of Demirjian's four dental development methods for forensic age
      estimation in South Australian sub-adults.
AB  - The aim of this study was to compare the accuracy of Demirjian's four dental
      development methods for forensic age assessment in a South Australian population.
      The sample comprised orthopantomograms (OPGs) of 408 sub-adult individuals (211
      male; 197 female) with an age range of 4.9-14.5 years. The OPGs were obtained
      from various dental schools and clinics in urban Adelaide. The following
      Demirjian methods were evaluated: the original 7-tooth technique; the revised 7
      tooth system; the 4-tooth method; and the alternate 4-tooth approach. The left
      mandibular teeth in each OPG were assessed and rated according to the eight
      stages (A-H) defined and illustrated in Demirjian et al.(5) Differences between
      chronological and estimated ages were calculated for males and females
      separately; 95% confidence intervals of mean age differences were calculated and
      ANOVA used to assess the significance of mean differences. When comparing all
      four methods there were significant differences overall (and in individual age
      groups) between mean chronological and estimated age in both sexes. In addition,
      each method consistently overestimated chronological age. We also demonstrate
      that the accuracy of the dental age methods evaluated varies in different subsets
      of an Australian population, a finding that parallels previous research in other
      global populations. Based on our analyses we conclude that population-specific
      standards based on dental maturity curves, as opposed to estimated ages, would
      provide more accurate and statistically robust age estimations. 

PMID- 24112342
TI  - Awareness of the patients' rights by subjects on admission to a tertiary
      university hospital in Poland.
AB  - BACKGROUND: Knowledge of patients' rights is obligatory to create a partner-based
      relationship between the doctor and the patient. Therefore, we sought to evaluate
      the awareness of patients' rights by subjects admitted to a multidisciplinary
      university hospital in Poland. METHODS: This project was cross-sectional in
      design and conducted between 06.2012 and 09.2012. The study group comprised 275
      persons aged 57.4 +/- 15.3 years. A 21-item questionnaire based on legal
      regulations on patients' rights was applied. RESULTS: Over 80% of respondents
      were aware of their right to choose a treating physician, refusal of the proposed
      treatment, the choice of the place where the patient is treated, the right of
      access to medical records, free meals, pastoral care, ability to provide to third
      parties information about the state of health, as well as giving information to
      particular persons by phone. The least awareness was shown in relation to the
      form of giving consent (42.9%) or refusal of consent (50.5%) to treatment and the
      doctors' right to refuse the presence of a person close to the patient during
      treatment (16.4%). Factors of significant impact on the findings were
      participants' age and education level. CONCLUSIONS: Patients are characterized by
      a considerable awareness of their rights. From the point of view of health care
      system, the most important is knowledge of the laws related to the broad access
      to medical services, including choice of attending physician but also to obtain
      assistance in emergency situations of life and health care in each facility
      health, regardless of place of residence.

PMID- 24112341
TI  - Macroscopically detected female genital injury after consensual and non
      consensual vaginal penetration: a prospective comparison study.
AB  - OBJECTIVE: The aim of this study was to compare the prevalence, type and pattern
      of macroscopically detected female genital injury after consensual and non
      consensual vaginal penetration to further an understanding of the forensic
      significance of genital injury in women reporting sexual assault. A secondary aim
      was to identify any effect of a range of possible variables upon the likelihood
      of genital injury resulting from vaginal penetrative sexual intercourse. STUDY
      DESIGN: Two groups of reproductive age women (aged 18-45 years) were
      prospectively recruited within 72 h of a single episode of vaginal penetrative
      sex, and macroscopically examined for the presence of bruises, abrasions and
      lacerations at twelve external and internal genital sites. Forty one women who
      presented for forensic examination after reporting a sexual assault to police
      were recruited to the non-consensual group and 81 women who presented for routine
      cervical screening or with sexual health concerns to a primary health care
      service to the consensual group. Each group was examined by a different group of
      doctors, all of whom were experienced in both forensic genital examination and
      gynaecological examination of healthy and diseased sexually active women. Data
      collection and examination protocols were the same for both groups. RESULTS: The
      key finding was a statistically significant difference in genital injury
      prevalence between women who were vaginally penetrated non-consensually and
      consensually; 53.7% of the non-consensual group (22/41) and 9.9% of the
      consensual group (8/81) were found to have at least one genital injury [OR 10.57,
      CI (4.07, 27.42), p < 0.00001]. Penetration with finger/s and possible pre
      existing genital 'infection' were found to be significantly associated with the
      presence of injury in the univariate analysis after adjusting for consent.
      Logistic regression demonstrated that women penetrated without consent were 19.5
      times more likely to sustain at least one genital injury, than those penetrated
      consensually [OR 19.53, CI (6.03, 63.24)] and that a penetration scenario that
      included finger/s was 4.2 times more likely to result in at least one genital
      injury than penetration without finger involvement [OR 4.25, CI (1.42, 12.78)],
      when controlling for other variables in the model. Whilst a comparatively low
      injury prevalence in the consensual group limited interpretation, results
      revealed possible differences in genital injury typology and pattern resulting
      from non-consensual and consensual vaginal penetration. Lacerations were seen
      after both consensual and non-consensual vaginal penetration, while abrasions and
      bruises were seen exclusively in the non-consensual group. CONCLUSION: This study
      demonstrated a significant consent group difference in genital injury prevalence
      and the highest macroscopically detected genital injury prevalence rate resulting
      from non-consensual vaginal penetration identified to date. Results also indicate
      that vaginal penetration with finger/s increases the likelihood of sex-related
      injury. The difference in type of injury sustained as a result of non-consensual
      and consensual vaginal penetration was an unexpected finding, and warrants
      further investigation. These results highlight the importance of a standardised
      means of detecting genital injury based on consistent injury definitions,
      examination protocols, and examiner experience and suggest that macroscopic
      genital examination may be uniquely placed to detect consent group differences in
      injury typology and pattern if they exist.

PMID- 24112343
TI  - Osteometric sex determination of burned human skeletal remains.
AB  - Sex determination of human burned skeletal remains is extremely hard to achieve
      because of heat-related fragmentation, warping and dimensional changes. In
      particular, the latter is impeditive of osteometric analyses that are based on
      references developed on unburned bones. New osteometric references were thus
      obtained which allow for more reliable sex determinations. The calcined remains
      of cremated Portuguese individuals were examined and specific standard
      measurements of the humerus, femur, talus and calcaneus were recorded. This
      allowed for the compilation of new sex discriminating osteometric references
      which were then tested on independent samples with good results. Both the use of
      simple section points and of logistic regression equations provided successful
      sex classification scores. These references may now be used for the sex
      determination of burned skeletons. Its reliability is highest for contemporary
      Portuguese remains but nonetheless these results have important repercussion for
      forensic research. More conservative use of these references may also prove
      valuable for other populations as well as for archaeological research. 

PMID- 24112344
TI  - Pink tooth phenomenon: an enigma?
AB  - BACKGROUND: The appearance of pink teeth is a common phenomenon which has been
      observed after death in certain circumstances on post-mortem examination. Extra
      fibrinolytic activity of pulp facilitates rapid breakdown of red blood cells and
      diffusion of hemoglobin and its derivatives to flow into dentine. METHODS AND
      RESULTS: We reviewed various studies on pink tooth phenomenon which have stated
      the various factors that lead to pink tooth formation. Most of the authors have
      stressed that post-mortem pink teeth must not be considered as a reliable
      odontological parameter for determining cause of death. CONCLUSION: No
      correlation has been found between the occurrence of pink teeth and the cause of
      death but condition of the surroundings certainly plays an important role in the
      development of this phenomenon. This paper reviews the factors and conditions
      responsible for formation of pink teeth.

PMID- 24112345
TI  - The development of a tool for assessing the quality of closed circuit camera
      footage for use in forensic gait analysis.
AB  - Gait analysis from closed circuit camera footage is now commonly used as evidence
      in criminal trials. The biomechanical analysis of human gait is a well
      established science in both clinical and laboratory settings. However, closed
      circuit camera footage is rarely of the quality of that taken in the more
      controlled clinical and laboratory environments. The less than ideal quality of
      much of this footage for use in gait analysis is associated with a range of
      issues, the combination of which can often render the footage unsuitable for use
      in gait analysis. The aim of this piece of work was to develop a tool for
      assessing the suitability of closed circuit camera footage for the purpose of
      forensic gait analysis. A Delphi technique was employed with a small sample of
      expert forensic gait analysis practitioners, to identify key quality elements of
      CCTV footage used in legal proceedings. Five elements of the footage were
      identified and then subdivided into 15 contributing sub-elements, each of which
      was scored using a 5-point Likert scale. A Microsoft Excel worksheet was
      developed to calculate automatically an overall score from the fifteen sub
      element scores. Five expert witnesses experienced in using CCTV footage for gait
      analysis then trialled the prototype tool on current case footage. A
      repeatability study was also undertaken using standardized CCTV footage. The
      results showed the tool to be a simple and repeatable means of assessing the
      suitability of closed circuit camera footage for use in forensic gait analysis.
      The inappropriate use of poor quality footage could lead to challenges to the
      practice of forensic gait analysis. All parties involved in criminal proceedings
      must therefore understand the fitness for purpose of any footage used. The
      development of this tool could offer a method of achieving this goal, and help to
      assure the continued role of forensic gait analysis as an aid to the
      identification process. 

PMID- 24112346
TI  - Chemical submission to commit robbery: a series of involuntary intoxications with
      flunitrazepam in Asian travellers in Brussels.
AB  - Between January 17, 2003 and August 29, 2003, the Emergency Department admitted a
      patient who had been surreptitiously intoxicated and robbed of his valuables
      every Friday. The first cases were considered anecdotal, but criminal activity
      was rapidly suspected. The cohort includes 16 male Asian patients aged 28-50
      years. All the victims had just arrived in Brussels through one of the main rail
      station of the town and were admitted via the emergency ambulance service from
      different locations in the centre of Brussels around the CHU Saint-Pierre
      Hospital. Haemodynamic parameters upon admission were within normal limits. The
      Glasgow Coma Scale was equal or higher than 9/15 in 14 of the 16 victims.
      Toxicology screening obtained in 12 patients revealed the presence of
      flunitrazepam, which was further quantified at levels ranging from 21 to 75
      MUg/l. One of the Japanese patients, who returned to Belgium afterwards for
      professional reasons, was approached by the police and accepted to press charges.
      This allowed the police to investigate and send undercover agents to the railway
      station on Friday afternoons and evenings. They found a person who was offering
      welcome cookies to Asian travellers. He arrived from Amsterdam and returned once
      his crime was committed. Flunitrazepam is well known as a rape drug. We report a
      series of victims in whom flunitrazepam was used to facilitate robbery. 

PMID- 24112347
TI  - Improvement of short tandem repeat analysis of samples highly contaminated by
      humic acid.
AB  - We investigated several methods for obtaining successful short tandem repeat
      (STR) results from high-humic acid (HA)-content samples. DNA purification
      efficiency was tested for QIAquick((r)) PCR Purification, QIAamp((r)) DNA
      Investigator and PrepfilerTM Forensic DNA Extraction kits. HA-removal capacity of
      Inhibitor Remover and InhibitEX((r)) Tablet was tested. Experiments on overcoming
      HA effects on STR amplification were conducted using an AmpliTaq Gold((r)) DNA
      Polymerase and a TaKaRa Ex TaqTM Hot Start Version (Ex Taq HS) with BSA addition.
      QIAquick kit was most efficient in HA removal and Ex Taq HS showed high
      resistance to HA. Increasing the amounts of Taq polymerases and BSA addition were
      shown to be efficient in overcoming PCR inhibition, but BSA addition was superior
      to the former method. Inhibitor Remover and InhibitEX((r)) Tablet did not
      positively affect the STR results. This study will help achieve better STR
      results with high-HA-content samples. 

PMID- 24112348
TI  - Child homicide in Cairo from 2006 to 2010: characteristics and trends.
AB  - BACKGROUND: Crimes towards children have drawn public attention over the decades.
      Several studies have been conducted to determine the risk factors of victimizing
      children. Conducting studies of this crime in Cairo, the capital city of Egypt,
      would help in understanding the motives behind it in such a densely populated
      area. RESEARCH DESIGN AND METHODOLOGY: A review of death charts was conducted in
      Zeinhom morgue in the years of 2006-2010 to study the trends and characteristics
      of child homicide in Cairo. The cut-off for a child age was at 18 years. Data
      related to the victim and offender was collected. RESULTS: Child homicides
      represented 7.97% of total child deaths in the studied period. Most of them (25%)
      fall in the age group of 1-6 years. Females were the majority in the age group of
      12-18 years (89%). The offender was the father in 28% of cases and the cause of
      death was mainly trauma to the head (42%). CONCLUSION: Further studies should be
      conducted to discern the risk factors of this crime in Cairo with special
      considerations to the motives behind murdering females in teen ages.

PMID- 24112349
TI  - Evaluation of dental malpractice cases in Kerman province (2000-2011).
AB  - INTRODUCTION: Dental practitioners, like other health-care professionals, might
      engage with legal claims and be sued if patients are not satisfied with the
      dental treatment. The aim of this study was to provide data on dental malpractice
      claims in Kerman, Iran, from 2000 to 2011. MATERIALS AND METHODS: In the present
      descriptive cross-sectional research, a retrospective evaluation was carried out
      of dental malpractice claims in Kerman, Iran, during 2000-2011, based on the
      decisions of expert committees in medical malpractice cases by the Kerman Legal
      Medicine Organization and the Medical Council of the Islamic Republic of Iran. A
      valid and reliable questionnaire was designed in three sections, based on
      previous studies. The SPSS 18 software program was used for data analysis.
      RESULTS: During the 11-year period, 64 decisions had been taken in relation to
      dental malpractices. The majority of complaints involved fixed prosthodontics and
      oral surgery usually by private practice and general dental practitioners. In
      56.7% of clinical cases and 40% of non-clinical cases of malpractice claims,
      dental practitioners had been found guilty. CONCLUSIONS: Like all other medical
      staff, dental practitioners are under the obligation to comply with the laws of
      the country they practice. They also have to adhere to ethical principles as well
      as the acceptable standards and protocols of diagnosis and treatment. These data
      can alert them to the need for greater care and professionalism when treating
      their patients.

PMID- 24112351
TI  - Persistent genital arousal disorder-update on the monster sexual dysfunction.

PMID- 24112350
TI  - Sequentially aerated membrane biofilm reactors for autotrophic nitrogen removal:
      microbial community composition and dynamics.
AB  - Membrane-aerated biofilm reactors performing autotrophic nitrogen removal can be
      successfully applied to treat concentrated nitrogen streams. However, their
      process performance is seriously hampered by the growth of nitrite oxidizing
      bacteria (NOB). In this work we document how sequential aeration can bring the
      rapid and long-term suppression of NOB and the onset of the activity of anaerobic
      ammonium oxidizing bacteria (AnAOB). Real-time quantitative polymerase chain
      reaction analyses confirmed that such shift in performance was mirrored by a
      change in population densities, with a very drastic reduction of the NOB
      Nitrospira and Nitrobacter and a 10-fold increase in AnAOB numbers. The study of
      biofilm sections with relevant 16S rRNA fluorescent probes revealed strongly
      stratified biofilm structures fostering aerobic ammonium oxidizing bacteria (AOB)
      in biofilm areas close to the membrane surface (rich in oxygen) and AnAOB in
      regions neighbouring the liquid phase. Both communities were separated by a
      transition region potentially populated by denitrifying heterotrophic bacteria.
      AOB and AnAOB bacterial groups were more abundant and diverse than NOB, and
      dominated by the r-strategists Nitrosomonas europaea and Ca. Brocadia
      anammoxidans, respectively. Taken together, the present work presents tools to
      better engineer, monitor and control the microbial communities that support
      robust, sustainable and efficient nitrogen removal. 

PMID- 24112352
TI  - Which is first? The controversial issue of precedence in the treatment of male
      sexual dysfunctions.
AB  - INTRODUCTION: In male sexual dysfunction (MSD), the presence of sexual
      comorbidities is relatively frequent. However, what is still a matter of
      controversy is what the first-line therapy in these patients should be. METHODS:
      Three scientists and the editor of the Controversies section, all experts in the
      medical treatment of MSD, present different perspectives on the use of
      phosphodiesterase type 5 inhibitors (PDE5), testosterone and dapoxetine in
      erectile dysfunction (ED), hypogonadism, and premature ejaculation (PE). The
      psychological aspects are discussed by an outstanding expert in psychosexology.
      MAIN OUTCOME MEASURE: Expert opinion supported by the critical review of the
      currently available literature. RESULTS: Testosterone should be used before PDE5s
      in hypogonadal men with comorbid ED; PDE5s should be used before dapoxetine in PE
      patients with comorbid ED, and counseling should be offered to all subjects with
      MSD. CONCLUSIONS: Although the answer to the question "which should be first?" is
      controversial in almost all MSDs, intuition, experience, and evidence should
      guide the choice of which treatment should be used first. This decision is highly
      critical in influencing the therapeutic outcome as well the patient's and
      couple's adherence to treatment.

PMID- 24112354
TI  - Sexuality and sexual pleasure after sexual assault.

PMID- 24112355
TI  - Factors that influence activities of daily living in the elderly with probable
      dementia.
AB  - The purpose of this study was to identify the factors that influence activities
      of daily living (ADL) in the elderly with probable dementia. The participants
      were 152 older adults who voluntarily visited a hospital to participate in a
      national dementia free screening programme. General characteristics, health
      related characteristics, ADL, Mini-Mental State Examination Korean Consortium
      (MMSE-KC) and the Geriatric Depression Scale (GDS) score were evaluated in this
      study. The data were analysed using independent t-tests, Pearson's correlation
      and stepwise multiple regression. The ADL score of the participants was 14.3, and
      88.2% of the participants were severe cognitive disorder. ADL scores were
      positively related with MMSE-KC scores (r = 0.35, P < 0.001) and negatively with
      GDS scores (r = -0.20, P = 0.014). Factors that influenced ADL were faecal and
      urinary incontinence, regularity of exercise, MMSE-KC score and stroke history;
      these five variables explained 30.8% of the ADL score for the elderly with
      probable dementia. Multidisciplinary interventions are essential to improve the
      ADL and prevent deterioration of cognitive function in elderly patients with
      probable dementia.

PMID- 24112357
TI  - Isolated hydatid disease of the breast: fine-needle aspiration cytologic
      diagnosis in a clinically unsuspected case.

PMID- 24112356
TI  - Using biogeographical history to inform conservation: the case of Preble's meadow
      jumping mouse.
AB  - The last Pleistocene deglaciation shaped temperate and boreal communities in
      North America. Rapid northward expansion into high latitudes created distinctive
      spatial genetic patterns within species that include closely related groups of
      populations that are now widely spread across latitudes, while longitudinally
      adjacent populations, especially those near the southern periphery, often are
      distinctive due to long-term disjunction. Across a spatial expanse that includes
      both recently colonized and long-occupied regions, we analysed molecular
      variation in zapodid rodents to explore how past climate shifts influenced
      diversification in this group. By combining molecular analyses with species
      distribution modelling and tests of ecological interchangeability, we show that
      the lineage including the Preble's meadow jumping mouse (Zapus hudsonius
      preblei), a US federally listed taxon of conservation concern, is not restricted
      to the southern Rocky Mountains. Rather, populations along the Front Range are
      part of a single lineage that is ecologically indistinct and extends to the far
      north. Of the 21 lineages identified, this Northern lineage has the largest
      geographical range and low measures of intralineage genetic differentiation,
      consistent with recent northward expansion. Comprehensive sampling combined with
      coalescent-based analyses and niche modelling leads to a radically different view
      of geographical structure within jumping mice and indicates the need to re
      evaluate their taxonomy and management. This analysis highlights a premise in
      conservation biology that biogeographical history should play a central role in
      establishing conservation priorities. 

PMID- 24112358
TI  - The changing skill mix in nursing: considerations for and against different
      levels of nurse.
AB  - AIM: To investigate the current literature to gain an understanding of skill mix,
      why it is being manipulated and how it affects patient care and health-care
      costs. BACKGROUND: Due to workforce shortages, economic constraints and
      increasing patient acuity, employers are looking at methods of providing patient
      care whilst maintaining costs. Registered nurses make up a large percentage of
      the health-care budget. The manipulation of skill mix (i.e. the percentage of
      registered nurses available for patient care) is seen as one method of managing
      the increasing cost whilst still ensuring patient care. EVALUATION: Research
      literature was used to determine the current use of skill mix and its impact on
      patient care and health-care costs. KEY ISSUE: The use of a higher proportion of
      registered nurses is associated with better health outcomes, shorter length of
      stay and reduced patient morbidity. CONCLUSION: Economic savings from
      substituting registered nurses with other health professionals may be offset by
      increased patient length of stay in hospital and increased patient mortality.
      IMPLICATIONS FOR NURSING MANAGEMENT: When evaluating nursing skill mix, a higher
      percentage of registered nurses may result in health-care facility cost savings
      by providing a shorter length of stay and decreased patient complications.

PMID- 24112359
TI  - Incidence of and risk factors for neonatal jaundice among newborns in southern
      Nepal.
AB  - OBJECTIVE: To quantify the incidence of and risk factors for neonatal jaundice
      among infants referred for care from a rural, low-resource, population-based
      cohort in southern Nepal. METHODS: Study participants were 18,985 newborn infants
      born in Sarlahi District in southern Nepal from May 2003 through January 2006 who
      participated in a cluster-randomised, placebo-controlled, community-based trial
      to evaluate the effect of newborn chlorhexidine cleansing on neonatal mortality
      and morbidity. Jaundice was assessed based on visual assessment of the infant by
      a study worker and referral for care. Adjusted relative risks (RR) were estimated
      to identify risk factors for referral for neonatal jaundice using Poisson
      regression. RESULTS: The incidence of referral for neonatal jaundice was 29.3 per
      1000 live births (95% confidence interval: 26.9, 31.7). Male sex, high birth
      weight, breastfeeding patterns, warm air temperature, primiparity, skilled birth
      attendance, place of delivery, prolonged labour, oil massage, paternal education
      and ethnicity were significant risk factors (P-values < 0.01). After
      multivariable adjustment, sex, birth weight, difficulty feeding, prolonged
      labour, primiparity, oil massage, ambient air temperature and ethnicity remained
      important factors. Among infants with difficulty feeding, exclusive breastfeeding
      was a risk factor for neonatal jaundice, whereas exclusive breastfeeding was
      protective among infants with no report of difficulty feeding. CONCLUSIONS:
      Several known risk factors for neonatal jaundice in a low-resource setting were
      confirmed in this study. Unique observed associations of jaundice with ambient
      air temperature and oil massage may be explained by the opportunity for
      phototherapy based on the cultural practices of this study population. Future
      research should investigate the role of an infant's difficulty in feeding as a
      potential modifier in the association between exclusive breastfeeding and
      jaundice.

PMID- 24112360
TI  - The health, social and educational needs of children who have survived meningitis
      and septicaemia: the parents' perspective.
AB  - BACKGROUND: Survivors of bacterial meningitis and septicaemia can experience a
      range of after-effects. There is little published research on the needs and
      provision of aftercare for children surviving bacterial meningitis and
      septicaemia. METHODS: Mixed methods study employing a survey and follow-up
      interviews with a sample of survey participants recruited from Meningitis
      Research Foundation's member database and social media. RESULTS: Of 194 eligible
      survey respondents, 77% reported at least moderate short-term after-effects, and
      57% a need for aftercare or support. Most parents reported that their child
      received a hearing test (98%) and follow-up appointment with a paediatrician
      (66%). Psychosocial after-effects were most common and the greatest need was for
      educational support. About half of participants felt their children's needs for
      aftercare were met. We conducted interviews with 18 parents. Findings suggest
      access could be limited by: parents' inability to navigate systems in place,
      child's age, and delayed identification of sequelae. Parents felt a comprehensive
      explanation of possible after-effects on discharge from hospital was required,
      and found uncertain prognoses difficult. Good communication between professionals
      enabled a service tailored to the child's needs. CONCLUSIONS: Our study supports
      the NICE and SIGN guidelines and highlights areas for improvement in the
      aftercare of these children.

PMID- 24112362
TI  - Treatment of herpes zoster related corneal neovascularisation and lipid
      keratopathy by photodynamic therapy.
AB  - Traditionally, photodynamic therapy (PDT) has been used to treat choroidal
      neovascularisation. More recently, its use in corneal neovascularisation has
      provided promising clinical results. The major advantage of PDT is that it is
      minimally invasive, resulting in closure of the neovascular network without
      damaging the surrounding healthy tissue. This report describes the positive
      results of PDT, clinically and microstructurally, as imaged by in vivo confocal
      microscopy, for treating corneal neovascularisation with lipid keratopathy,
      secondary to herpes zoster infection. 

PMID- 24112361
TI  - Rapid effects of oestrogen on synaptic plasticity: interactions with actin and
      its signalling proteins.
AB  - Oestrogen rapidly enhances fast excitatory postsynaptic potentials, facilitates
      long-term potentiation (LTP) and increases spine numbers. Each effect likely
      contributes to the influence of the steroid on cognition and memory. In the
      present review, we first describe a model for the substrates of LTP that includes
      an outline of the synaptic events occurring during induction, expression and
      consolidation. Briefly, critical signalling pathways involving the small GTPases
      RhoA and Rac/Cdc42 are activated by theta burst-induced calcium influx and
      initiate actin filament assembly via phosphorylation (inactivation) of cofilin.
      Reorganisation of the actin cytoskeleton changes spine and synapse morphology,
      resulting in increased concentrations of AMPA receptors at stimulated contacts.
      We then use the synaptic model to develop a specific hypothesis about how
      oestrogen affects both baseline transmission and plasticity. Brief infusions of
      17beta-oestradiol (E2 ) reversibly stimulate the RhoA, cofilin phosphorylation
      and actin polymerisation cascade of the LTP machinery; blocking this eliminates
      the effects of the steroid on transmission. We accordingly propose that E2
      induces a weak form of LTP and thereby increases synaptic responses, a hypothesis
      that also accounts for how it markedly enhances theta burst induced potentiation.
      Although the effects of E2 on the cytoskeleton could be a result of the direct
      activation of small GTPases by oestrogen receptors on the synaptic membrane, the
      hormone also activates tropomyosin-related kinase B receptors for brain-derived
      neurotrophic factor, a neurotrophin that engages the RhoA-cofilin sequence and
      promotes LTP. The latter observations raise the possibility that E2 produces its
      effects on synaptic physiology via transactivation of neighbouring receptors that
      have prominent roles in the management of spine actin, synaptic physiology and
      plasticity. 

PMID- 24112363
TI  - FlexiTerm: a flexible term recognition method.
AB  - BACKGROUND: The increasing amount of textual information in biomedicine requires
      effective term recognition methods to identify textual representations of domain
      specific concepts as the first step toward automating its semantic
      interpretation. The dictionary look-up approaches may not always be suitable for
      dynamic domains such as biomedicine or the newly emerging types of media such as
      patient blogs, the main obstacles being the use of non-standardised terminology
      and high degree of term variation. RESULTS: In this paper, we describe FlexiTerm,
      a method for automatic term recognition from a domain-specific corpus, and
      evaluate its performance against five manually annotated corpora. FlexiTerm
      performs term recognition in two steps: linguistic filtering is used to select
      term candidates followed by calculation of termhood, a frequency-based measure
      used as evidence to qualify a candidate as a term. In order to improve the
      quality of termhood calculation, which may be affected by the term variation
      phenomena, FlexiTerm uses a range of methods to neutralise the main sources of
      variation in biomedical terms. It manages syntactic variation by processing
      candidates using a bag-of-words approach. Orthographic and morphological
      variations are dealt with using stemming in combination with lexical and phonetic
      similarity measures. The method was evaluated on five biomedical corpora. The
      highest values for precision (94.56%), recall (71.31%) and F-measure (81.31%)
      were achieved on a corpus of clinical notes. CONCLUSIONS: FlexiTerm is an open
      source software tool for automatic term recognition. It incorporates a simple
      term variant normalisation method. The method proved to be more robust than the
      baseline against less formally structured texts, such as those found in patient
      blogs or medical notes. The software can be downloaded freely at
      http://www.cs.cf.ac.uk/flexiterm.

PMID- 24112364
TI  - Risk factors for cholera transmission in Haiti during inter-peak periods:
      insights to improve current control strategies from two case-control studies.
AB  - Two community-based density case-control studies were performed to assess risk
      factors for cholera transmission during inter-peak periods of the ongoing
      epidemic in two Haitian urban settings, Gonaives and Carrefour. The strongest
      associations were: close contact with cholera patients (sharing latrines,
      visiting cholera patients, helping someone with diarrhoea), eating food from
      street vendors and washing dishes with untreated water. Protective factors were:
      drinking chlorinated water, receiving prevention messages via television, church
      or training sessions, and high household socioeconomic level. These findings
      suggest that, in addition to contaminated water, factors related to direct and
      indirect inter-human contact play an important role in cholera transmission
      during inter-peak periods. In order to reduce cholera transmission in Haiti
      intensive preventive measures such as hygiene promotion and awareness campaigns
      should be implemented during inter-peak lulls, when prevention activities are
      typically scaled back.

PMID- 24112365
TI  - Plasma cell hepatitis induced by the termination of antiviral therapy for
      recurrent hepatitis C after living donor liver transplantation.
AB  - Plasma cell hepatitis (PCH) is an idiopathic disorder characterized by plasma
      cell infiltration in the allografts of patients who have undergone liver
      transplantation. Although an increasing number of cases of PCH have been reported
      in liver transplant recipients with hepatitis C recurrence treated with
      interferon, it is unclear whether PCH is induced by interferon itself. Here, we
      describe the cases of two patients who developed PCH just after the termination
      of antiviral therapy for recurrent hepatitis C after living donor liver
      transplantation. Liver dysfunction appeared at 1 month in one patient and 2
      months in the other patient after pegylated interferon plus ribavirin therapy,
      and liver histology showed interface hepatitis with plasma cell-rich lymphoid
      aggregates. Both patients recovered after steroid therapy and achieved sustained
      virological response. These cases suggest that PCH could be induced by the
      alteration of the immune condition resulting from the termination of antiviral
      therapy. PCH should be considered when the transaminase levels increase after
      antiviral therapy, and it should be carefully distinguished from hepatitis C
      relapse. 

PMID- 24112366
TI  - Arachidic acid in extender improves post-thaw parameters of cryopreserved Nili
      Ravi buffalo bull semen.
AB  - Cryopreservation process reduces lipids and phospholipids from buffalo bull
      spermatozoa. It was therefore hypothesized that supplementation of fatty acid to
      extender may improve the post-thaw quality of buffalo semen. The objective was to
      evaluate the effect of arachidic acid supplementation in extender on post-thaw
      quality of buffalo bull (Bubalus bubalis) spermatozoa. Semen was collected from
      three adult Nili-Ravi buffalo bulls of similar age group with artificial vagina
      (42 degrees C) for 3 weeks (replicate). Qualified semen ejaculates (n = 18) were
      split into four aliquots and diluted in tris-citric acid extender containing 0.0
      (control), 5.0, 10.0 and 20.0 ng/ml at 37 degrees C having approximately 50 *
      10(6) spermatozoa/ml. Diluted semen was cooled to 4 degrees C in 2 h and
      equilibrated for 4 h at 4 degrees C. Cooled semen was filled in 0.5-ml straws at
      4 degrees C, kept on liquid nitrogen vapours for 10 min and plunged in liquid
      nitrogen for storage. Thawing of frozen semen was performed after 24 h at 37
      degrees C for 30 s. Sperm progressive motility (%) was improved in a dose
      dependent manner by supplementing arachidic acid at 5.0, 10.0 and 20.0 ng/ml
      compared with control. Structural and functional integrity of sperm plasma
      membrane (%), number of acrosome-intact live sperm (%) and sperm chromatin
      integrity (%) were better (p < 0.05) in extender having 5.0 ng/ml of arachidic
      acid compared with control. At 10.0 ng/ml, these values did not vary (p > 0.05)
      from those at 5.0 ng/ml. Further improvement in structural and functional
      integrity of sperm plasma membrane, number of acrosome-intact live sperm and
      chromatin integrity was observed at 20.0 ng/ml of arachidic acid in extender. In
      conclusion, arachidic acid supplementation in extender improved the post-thaw
      quality parameters of cryopreserved Nili-Ravi buffalo bull spermatozoa. Among the
      arachidic acid concentrations studied, maximum improvement in post-thaw semen
      quality parameters was observed at 20.0 ng/ml. 

PMID- 24112367
TI  - Cellular cannibalism in central and peripheral giant cell granuloma of the oral
      cavity can predict biological behavior of the lesion.
AB  - BACKGROUND: Cancer cannibalism is used to differentiate benign tumors from
      malignant, but recently the phenomenon has been demonstrated in giant cell tumor
      of tendon sheath (localized type). Microscopically and pathogenetically, this
      tumor is similar to central giant cell granuloma (CGCG) and peripheral giant cell
      granuloma (PGCG) of oral cavity. Hence, attempt has been made to study the
      cannibalistic giant cells (GCs) in CGCG and PGCG with their correlation with the
      biological behavior. METHODS: Surgically treated 16 CGCG and 23 PGCG cases with
      adequate clinical and radiographic documentation were selected. Quantification of
      cannibalistic GCs was performed using routine HE stain. Hundred GCs were examined
      in each section, and number of cannibalistic cells was expressed in percentage.
      Ten cases were randomly selected for further immunohistochemical analysis with
      CD68 and bcl-2. RESULTS: Cannibalism was found in all the cases (100%). The
      frequency of occurrence of cannibalistic GCs ranged from 20% to 56% with a mean
      of 33.62 +/- 8.9. CGCG showed significantly higher mean cannibalistic GC
      frequency (38.06 +/- 10.15) than PGCG (30.04 +/- 5.63). In aggressive CGCG, mean
      cannibalistic GC frequency was significantly higher (42.20 +/- 10.4) than non
      aggressive type (31.17 +/- 6.014). Similarly, recurrent cases showed
      significantly higher mean cannibalistic cell frequency (43 +/- 6.26) than non
      recurrent cases (30.81 +/- 6.66). Immunohistochemistry results showed histiocytic
      nature of GCs as well as mononuclear cells. The internalized cells did not
      expressed bcl-2, suggesting that the internalization induces apoptotic cell
      death. CONCLUSION: Assessment of frequency of cannibalistic cells in CGCG and
      PCGC could help in predicting the biological behavior of the tumor.

PMID- 24112368
TI  - Nursing diagnoses determined by first year students: a vignette study.
AB  - PURPOSE: The study aimed to determine the ability of first year students in
      identifying nursing diagnoses. METHODS: In a descriptive evaluation study, an
      expert-validated vignette containing 18 nursing diagnoses was used. RESULTS: The
      students determined 15 nursing diagnoses. The highest percentages of diagnoses
      identified were disturbed sleep pattern and nutrition imbalance. Students also
      considered medical diagnoses as nursing diagnoses: hypertension and tachycardia.
      CONCLUSIONS: Despite the fact that students were only at the end of their first
      semester and had limited clinical experience, they successfully identified the
      majority of nursing diagnoses. IMPLICATIONS FOR NURSING PRACTICE: Patient case
      study vignettes are recommended for education. To foster students' knowledge and
      experience, it is also suggested that evaluating nursing diagnoses in clinical
      practicals becomes a requirement.

PMID- 24112370
TI  - Afferent loop syndrome successfully treated by endoscopic ultrasound-guided
      transgastric drainage.

PMID- 24112369
TI  - Novel region discovery method for Infinium 450K DNA methylation data reveals
      changes associated with aging in muscle and neuronal pathways.
AB  - We describe a methodology for detecting differentially methylated regions (DMRs)
      and variably methylated regions (VMRs), in data from Infinium 450K arrays that
      are very widely used in epigenetic studies. Region detection is more specific
      than single CpG analysis as it increases the extent of common findings between
      studies, and is more powerful as it reduces the multiple testing problem inherent
      in epigenetic whole-genome association studies (EWAS). In addition, results
      driven by single erroneous probes are removed. We have used multiple publicly
      available Infinium 450K data sets to generate a consensus list of DMRs for age,
      supporting the hypothesis that aging is associated with specific epigenetic
      modifications. The consensus aging DMRs are significantly enriched for muscle
      biogenesis pathways. We find a massive increase in VMRs with age and in regions
      of the genome associated with open chromatin and neurotransmission. Old age VMRs
      are significantly enriched for neurotransmission pathways. EWAS studies should
      investigate the role of this interindividual variation in DNA methylation, in the
      age-associated diseases of sarcopenia and dementia. 

PMID- 24112371
TI  - Remote vibrotactile noise improves light touch sensation in stroke survivors'
      fingertips via stochastic resonance.
AB  - BACKGROUND AND PURPOSE: Stroke rehabilitation does not often integrate both
      sensory and motor recovery. While subthreshold noise was shown to enhance sensory
      signal detection at the site of noise application, having a noise-generating
      device at the fingertip to enhance fingertip sensation and potentially enhance
      dexterity for stroke survivors is impractical, since the device would interfere
      with object manipulation. This study determined if remote application of
      subthreshold vibrotactile noise (away from the fingertips) improves fingertip
      tactile sensation with potential to enhance dexterity for stroke survivors.
      METHODS: Index finger and thumb pad sensation was measured for ten stroke
      survivors with fingertip sensory deficit using the Semmes-Weinstein Monofilament
      and Two-Point Discrimination Tests. Sensation scores were measured with noise
      applied at one of three intensities (40%, 60%, 80% of the sensory threshold) to
      one of four locations of the paretic upper extremity (dorsal hand proximal to the
      index finger knuckle, dorsal hand proximal to the thumb knuckle, dorsal wrist,
      volar wrist) in a random order, as well as without noise at beginning (Pre) and
      end (Post) of the testing session. RESULTS: Vibrotactile noise of all intensities
      and locations instantaneously and significantly improved Monofilament scores of
      the index fingertip and thumb tip (p < .01). No significant effect of the noise
      was seen for the Two-Point Discrimination Test scores. CONCLUSIONS: Remote
      application of subthreshold (imperceptible) vibrotactile noise at the wrist and
      dorsal hand instantaneously improved stroke survivors' light touch sensation,
      independent of noise location and intensity. Vibrotactile noise at the wrist and
      dorsal hand may have enhanced the fingertips' light touch sensation via
      stochastic resonance and interneuronal connections. While long-term benefits of
      noise in stroke patients warrants further investigation, this result demonstrates
      potential that a wearable device applying vibrotactile noise at the wrist could
      enhance sensation and grip ability without interfering with object manipulation
      in everyday tasks.

PMID- 24112373
TI  - [Space occupying lesions in the liver and spleen in a 41-year-old man].

PMID- 24112372
TI  - Self-reported sleep disturbances in renal transplant recipients.
AB  - BACKGROUND: Poor sleep quality (SQ) and daytime sleepiness (DS) are common in
      renal transplant (RTx) recipients; however, related data are rare. This study
      describes the prevalence and frequency of self-reported sleep disturbances in RTx
      recipients. METHODS: This cross-sectional study included 249 RTx recipients
      transplanted at three Swiss transplant centers. All had reported poor SQ and / or
      DS in a previous study. With the Survey of Sleep (SOS) self-report questionnaire,
      we screened for sleep and health habits, sleep history, main sleep problems and
      sleep-related disturbances. To determine a basis for preliminary sleep diagnoses
      according to the International Classification of Sleep Disorders (ICSD), 164
      subjects were interviewed (48 in person, 116 via telephone and 85 refused).
      Descriptive statistics were used to analyze the data and to determine the
      frequencies and prevalences of specific sleep disorders. RESULTS: The sample had
      a mean age of 59.1 +/- 11.6 years (60.2% male); mean time since Tx was 11.1 +/-
      7.0 years. The most frequent sleep problem was difficulty staying asleep (49.4%),
      followed by problems falling asleep (32.1%). The most prevalent sleep disturbance
      was the need to urinate (62.9%), and 27% reported reduced daytime functionality.
      Interview data showed that most suffered from the first ICSD category: insomnias.
      CONCLUSION: Though often disregarded in RTx recipients, sleep is an essential
      factor of wellbeing. Our findings show high prevalences and incidences of
      insomnias, with negative impacts on daytime functionality. This indicates a need
      for further research on the clinical consequences of sleep disturbances and the
      benefits of insomnia treatment in RTx recipients.

PMID- 24112374
TI  - Description of extreme longevity in the Balearic Islands: Exploring a potential
      Blue Zone in Menorca, Spain.
AB  - AIM: We aimed to determine whether there was a Blue Zone, an area characterized
      by extreme longevity, in Menorca, Spain. METHODS: We explored official statistics
      of the Balearic Islands, Spain, and calculated life expectancy from 1991 to 2009,
      by sex and island, among other demographic estimators. RESULTS: The life
      expectancy at birth in Menorca reached a peak in 2007 with 82.3 years, but since
      2001 in females and 2007 in males, it plateaued and then descended. The
      percentage of centenarians in Es Migjorn Gran was 0.17% in 2001, only because of
      the 0.33% male contribution, and it returned to within the average Balearic
      rates. There is no record of any other surviving centenarian after 2006 in Es
      Migjorn Gran. Results obtained with other demographic indices are confirmatory.
      CONCLUSIONS: It appears there was no extreme longevity or Blue Zone in Es Migjorn
      Gran and the surrounding villages in Menorca.

PMID- 24112377
TI  - Newborn care behaviours and neonatal survival: evidence from sub-Saharan Africa.
AB  - OBJECTIVE: To review evidence from sub-Saharan Africa for the association between
      the practice or promotion of essential newborn care behaviours and neonatal
      survival. METHODS: We searched MEDLINE for English language, peer-reviewed
      literature published since 2005. The study population was neonates residing in a
      sub-Saharan Africa country who were not HIV positive. Outcomes were all-cause
      neonatal or early neonatal mortality or one of the three main causes of neonatal
      mortality: complications of preterm birth, infections and intrapartum-related
      neonatal events. Interventions included were the practice or promotion of
      recommended newborn care behaviours including warmth, hygiene, breastfeeding,
      resuscitation and management of illness. We included study designs with a
      concurrent comparison group. Study quality was assessed using the Cochrane EPOC
      or Newcastle-Ottawa tools and summarised using GRADE. RESULTS: Eleven papers met
      the search criteria and most were at low risk of bias. We found evidence that
      delivering on a clean surface, newborn resuscitation, early initiation and
      exclusive breastfeeding, Kangaroo Mother Care (KMC) for low-birthweight babies,
      and distribution of clean delivery kits were associated with reduced risks of
      neonatal mortality or the main causes of neonatal mortality. There was evidence
      that training community birth attendants in resuscitation and administering
      antibiotics, and establishing women's groups can improve neonatal survival.
      CONCLUSION: There is a remarkable lack of robust evidence from sub-Saharan Africa
      on the association between practice or promotion of newborn care behaviours and
      newborn survival.

PMID- 24112378
TI  - Midface composite defect: laterally based bilobed flap as a platform for a 3
      stage folded paramedian forehead flap.

PMID- 24112376
TI  - Activating mutations of GNAS in canine cortisol-secreting adrenocortical tumors.
AB  - BACKGROUND: Cushing's syndrome or hypercortisolism is a common endocrinopathy in
      dogs. In approximately 15% of cases, the disorder is caused by
      adrenocorticotropin (ACTH)-independent hypersecretion of cortisol by an
      adrenocortical tumor (AT). Without other explanation, the cortisol hypersecretion
      has been referred to as autonomous. OBJECTIVES: To investigate whether ACTH
      independent hypersecretion of cortisol may be associated with aberrant activation
      of the melanocortin 2 receptor (MC2R)-cyclic AMP (cAMP)-protein kinase A (PKA)
      pathway. ANIMALS: All analyses were performed on 44 cortisol-secreting ATs (14
      adenomas and 30 carcinomas) derived from dogs diagnosed with ACTH-independent
      hypercortisolism. METHODS: Mutation analysis was performed of genes encoding the
      stimulatory G protein alpha subunit (GNAS), MC2R, and PKA regulatory subunit 1A
      (PRKAR1A) in all ATs. RESULTS: Approximately one-third of all ATs harbored an
      activating mutation of GNAS. Missense mutations, known to result in constitutive
      activation, were present in codon 201 in 11 ATs, in codon 203 (1 AT), and in
      codon 227 (3 ATs). No functional mutations were found in MC2R and PRKAR1A.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Activation of cAMP signaling is a frequent
      event in canine cortisol-secreting ATs and may play a crucial role in both ACTH
      independent cortisol production and tumor formation. To the best of our
      knowledge, this is the first report of potentially causative mutations in canine
      cortisol-secreting ATs.

PMID- 24112375
TI  - Weight change upon once-daily initiation of insulin detemir with or without
      dietary intervention in overweight or obese insulin-naive individuals with type 2
      diabetes: results from the DIET trial.
AB  - AIMS: Weight gain upon insulin initiation is opposite to clinical goals in
      diabetes management. This trial aimed to determine the impact of modest dietary
      intervention on weight change and examine weight change in baseline body mass
      index strata when initiating once-daily insulin detemir (IDet) in overweight or
      obese insulin-naive individuals with type 2 diabetes (T2D). METHODS: DIET (Impact
      of Dietary Intervention on Weight Change in Subjects With Type 2 Diabetes) was a
      26-week, randomized, treat-to-target, stratified, controlled, open-label,
      multinational trial. Subjects were randomized 1 : 1 to either the IDet group,
      which received basic dietary and physical exercise advice at baseline, or the
      Diet+IDet group, which had additional dietary consultations with a certified
      dietician (three face-to-face meetings, three phone contacts). RESULTS: Mean
      estimated change in body weight from baseline +/- standard error (SE) was -1.05
      +/- 0.23 kg for Diet+IDet and -0.56 +/- 0.23 kg for IDet alone. Estimated mean
      difference was 0.49 kg (95% confidence interval: -0.15; 1.13, p = 0.132).
      Glycaemic control, measured by haemoglobin A1c (HbA1c) and fasting plasma
      glucose, improved similarly in both groups. Both groups reported variable
      reductions in caloric intake and overall physical activity levels. No difference
      in hypoglycaemia rates between groups was observed. CONCLUSION: This study
      suggests that a modest dietary intervention plus basic lifestyle advice, compared
      with basic lifestyle advice alone, resulted in similar weight change, efficacy,
      safety and tolerability when initiating IDet once daily in overweight or obese
      insulin-naive individuals with T2D.

PMID- 24112380
TI  - Nursing work environment in Saudi Arabia.
AB  - AIM: The purpose of this study was to assess the work environment as perceived by
      nurses in a large tertiary hospital in Saudi Arabia. BACKGROUND: The quality of
      patient care services has been associated with the quality of work environment of
      nurses. It is therefore important to assess the work environment in order to
      acquire baseline data and enable the institution to benchmark their status from
      established quality standards. METHOD: This study used a descriptive survey with
      1007 staff nurses across service units of a 1000-bed government-operated
      hospital. The American Association of Critical-Care Nurses (AACN) Healthy Work
      Environment Assessment Questionnaire was used for data collection. Scores were
      aggregated and interpreted. RESULT: Effective decision making, authentic
      leadership, appropriate staffing, true collaboration, skilled communication and
      meaningful recognition were rated as good (mean range 3.53-3.76). CONCLUSION:
      Healthy work environments mutually benefit patients, nurses, nurse managers,
      health care providers, the health team, administration, the institution and the
      community at large. IMPLICATIONS FOR NURSING MANAGEMENT: Valuable baseline data
      on the status of the work environment in this setting were generated. This should
      allow administrators and staff to work together in improving weaknesses and
      strengthening further whatever gains that are attained to ensure consistent
      provision of safe and quality patient care.

PMID- 24112381
TI  - Variability of nursing care by APR-DRG and by severity of illness in a sample of
      nine Belgian hospitals.
AB  - BACKGROUND: As soon as Diagnosis related Groups (DRG) were introduced in many
      hospital financing systems, most nursing research revealed that DRG were not very
      homogeneous with regard to nursing care. However, few studies are based on All
      Patient refined Diagnosis related Groups (APR-DRGs) and few of them use recent
      data. Objectives of this study are: (1) to evaluate if nursing activity is
      homogeneous by APR-DRG and by severity of illness (SOI) (2) to evaluate the
      outlier's rate associated with the nursing activity and (3) to compare nursing
      cost homogeneity per DRG and SOI. METHODS: Study done in 9 Belgian hospitals on a
      selection of APR-DRG with more than 30 patients (7 638 inpatient stays). The
      evaluation of the homogeneity is based on coefficients of variation (CV). The
      75th percentile + 1.5 * inter-quartile range was used to select high outliers.
      25th percentile -1.5 * inter-quartile range was used to select low outliers.
      Nursing costs per ward were distributed on inpatient stays of each ward following
      two techniques (the LOS vs. the number of nursing care minutes per stay).
      RESULTS: The homogeneity of LOS by DRG and by SOI is relatively good (CV: 0.56).
      The homogeneity of the nursing activity by DRG is less good (CVs between 0.36 and
      1.54) and is influenced by nursing activity outliers (high outliers' rate: 5.19%,
      low outliers' rate: 0.14%). The outlier's rate varies according to the studied
      variable. The high outliers' rate is higher for nursing activity than for LOS.
      The homogeneity of nursing costs is higher when costs are based on the LOS of
      patients than when based on minutes of nursing care (CVs between 0.26 and 1.46
      for nursing costs based on LOS and between 0.49 and 2.04 for nursing costs based
      on minutes of nursing care). CONCLUSIONS: It is essential that the calculation of
      nursing cost by stay and by DRG for hospital financing purposes was based on
      nursing activity data, that more reflect resources used in wards, and not on LOS
      data. The only way to obtain this information is the generalization of
      computerized nursing files.

PMID- 24112382
TI  - Phenol removal from refinery wastewater by mutant recombinant horseradish
      peroxidase.
AB  - Application of mutated recombinant horseradish peroxidase (HRP) for phenol
      removal from refinery effluents is reported. Recombinant HRP produced in
      Escherichia coli suffers from the disadvantage of lacking glycosylation, which
      affects its catalytic efficiency and stability toward inactivating parameters
      such as increased temperature and enhanced amounts of hydrogen peroxide. In the
      present study, the previously reported variant (in which Asn268 was substituted
      with Asp, N268D) with improved stability characteristics and catalytic efficiency
      was used to remove phenol from a petroleum refinery effluent. The presence and
      removal of phenol was studied by high-performance liquid chromatography; the
      precipitated oxidized phenol was also observed and removed from the sample by
      centrifugation. Results showed that the N268D variant can remove 61%, 67%, and
      81% of phenol from effluent in 1, 2, and 16 H, respectively. By exploiting the
      N268D mutant, removal of 50% phenol could be achieved in 42 Min, which was more
      than 22 times less than the treatment time required by native recombinant enzyme.

PMID- 24112379
TI  - Molecular characterization of trophic ecology within an island radiation of
      insect herbivores (Curculionidae: Entiminae: Cratopus).
AB  - The phytophagous beetle family Curculionidae is the most species-rich insect
      family known, with much of this diversity having been attributed to both co
      evolution with food plants and host shifts at key points within the early
      evolutionary history of the group. Less well understood is the extent to which
      patterns of host use vary within or among related species, largely because of the
      technical difficulties associated with quantifying this. Here we develop a
      recently characterized molecular approach to quantify diet within and between two
      closely related species of weevil occurring primarily within dry forests on the
      island of Mauritius. Our aim is to quantify dietary variation across populations
      and assess adaptive and nonadaptive explanations for this and to characterize the
      nature of a trophic shift within an ecologically distinct population within one
      of the species. We find that our study species are polyphagous, consuming a much
      wider range of plants than would be suggested by the literature. Our data suggest
      that local diet variation is largely explained by food availability, and locally
      specialist populations consume food plants that are not phylogenetically novel,
      but do appear to represent a novel preference. Our results demonstrate the power
      of molecular methods to unambiguously quantify dietary variation across
      populations of insect herbivores, providing a valuable approach to understanding
      trophic interactions within and among local plant and insect herbivore
      communities. 

PMID- 24112384
TI  - Foreign medical teams: what role can they play in response to a catastrophic
      disaster in the US?
AB  - Hurricane Katrina demonstrated that a catastrophic event in the continental
      United States (US) can overwhelm domestic medical response capabilities. The
      recent focus on response planning for a catastrophic earthquake in the New Madrid
      Seismic Zone and the detonation of an improvised nuclear device also underscore
      the need for improved plans. The purpose of this analysis is to identify the
      potential role of foreign medical teams (FMTs) in providing medical response to a
      catastrophic event in the US. We reviewed existing policies and frameworks that
      address medical response to catastrophic events and humanitarian emergencies and
      assess current response capabilities by a variety of FMTs. While several policies
      and plans outline the role of the US in providing medical assistance during
      foreign disasters, further planning is necessary to identify how the US will
      integrate foreign medical assistance during a domestic catastrophic event. We
      provide an overview of considerations related to federal roles and
      responsibilities for managing and integrating FMTs into the overarching domestic
      medical response to a catastrophic disaster occurring in the continental US.

PMID- 24112383
TI  - Evaluating gold standard corpora against gene/protein tagging solutions and
      lexical resources.
AB  - MOTIVATION: The identification of protein and gene names (PGNs) from the
      scientific literature requires semantic resources: Terminological and lexical
      resources deliver the term candidates into PGN tagging solutions and the gold
      standard corpora (GSC) train them to identify term parameters and contextual
      features. Ideally all three resources, i.e. corpora, lexica and taggers, cover
      the same domain knowledge, and thus support identification of the same types of
      PGNs and cover all of them. Unfortunately, none of the three serves as a
      predominant standard and for this reason it is worth exploring, how these three
      resources comply with each other. We systematically compare different PGN taggers
      against publicly available corpora and analyze the impact of the included lexical
      resource in their performance. In particular, we determine the performance gains
      through false positive filtering, which contributes to the disambiguation of
      identified PGNs. RESULTS: In general, machine learning approaches (ML-Tag) for
      PGN tagging show higher F1-measure performance against the BioCreative-II and
      Jnlpba GSCs (exact matching), whereas the lexicon based approaches (LexTag) in
      combination with disambiguation methods show better results on FsuPrge and
      PennBio. The ML-Tag solutions balance precision and recall, whereas the LexTag
      solutions have different precision and recall profiles at the same F1-measure
      across all corpora. Higher recall is achieved with larger lexical resources,
      which also introduce more noise (false positive results). The ML-Tag solutions
      certainly perform best, if the test corpus is from the same GSC as the training
      corpus. As expected, the false negative errors characterize the test corpora and 
      on the other hand - the profiles of the false positive mistakes characterize the
      tagging solutions. Lex-Tag solutions that are based on a large terminological
      resource in combination with false positive filtering produce better results,
      which, in addition, provide concept identifiers from a knowledge source in
      contrast to ML-Tag solutions. CONCLUSION: The standard ML-Tag solutions achieve
      high performance, but not across all corpora, and thus should be trained using
      several different corpora to reduce possible biases. The LexTag solutions have
      different profiles for their precision and recall performance, but with similar
      F1-measure. This result is surprising and suggests that they cover a portion of
      the most common naming standards, but cope differently with the term variability
      across the corpora. The false positive filtering applied to LexTag solutions does
      improve the results by increasing their precision without compromising
      significantly their recall. The harmonisation of the annotation schemes in
      combination with standardized lexical resources in the tagging solutions will
      enable their comparability and will pave the way for a shared standard.

PMID- 24112385
TI  - Role of sperm velocity variables associated with poultry breed in 'last male
      precedence'.
AB  - It is well known that when a hen mates with multiple roosters, it is the sperm of
      the last male that usually fertilizes most of the eggs ('last male precedence').
      Sperm quality varies between males within a breed, but also between breeds, and
      thus, sperm competitiveness after mating may depend on the breeds of the roosters
      involved. The aim of the present work was to identify differences in sperm
      competitiveness between breeds, especially with respect to motility. A multibreed
      mating model was used. Blue Andaluza (BA) and Black Castellana (BC) hens left for
      21 days with BA and BC roosters, respectively, were then left with Black-barred
      Andaluza (Bb) roosters for another 21 days (experimental groups hBA-rBC-rBb and
      hBC-rBA-rBb). Bb roosters (as the second breed replacing the first) fertilized
      the majority of eggs in both the hBC-rBA-rBb and hBA-rBC-rBb groups. The
      percentage of offspring sired by BA roosters (8.0%) was higher (p < 0.05) than
      the percentage of chicks sired by BC roosters (2.1%). The fertility of the BC
      hens in the hBC-rBA-rBb group was higher (p < 0.01) than that of the BA hens in
      the hBA-rBC-rBb group. No difference in sperm concentration was seen between the
      breeds. Within the rapid sperm subpopulation (sperm velocity, >50 MUm/s), Bb
      sperm showed a higher straight-line velocity (VSL) and average path velocity
      (VAP) (p < 0.05) than BC sperm. The VSL and VAP values for Bb and BA sperm were
      similar. In conclusion, the present results show that the sperm of the BA breed,
      traditionally regarded as of moderate fertility, compensates for this drawback
      via sperm movement characteristics that afford it an advantage in competition
      scenarios involving males of other breeds. The VSL and VAP of the rapid sperm
      subpopulation may play the most important role in securing last male precedence. 

PMID- 24112386
TI  - Narrowband UVB phototherapy for pediatric generalized pityriasis lichenoides.

PMID- 24112387
TI  - Precompetitive assessment of heart rate variability in elite female athletes
      during play offs.
AB  - BACKGROUND: Heart rate variability (HRV) has been rarely applied in elite
      athletes prior to competition. The aim of this study was to examine the changes
      in HRV in elite female volleyball players before a stressful match during play
      offs and to evaluate the impact on sport-specific performance. METHODS: A short
      term resting HRV analysis was applied right after the night sleep in ten female
      athletes 1 and 2 days prior to the match and the day of the competition. RESULTS:
      Approaching the decisive match, RR interval, resting heart rate (HR), pNN50,
      rMSDD and SD1 did not significantly vary. SD2 significantly increased in
      comparison with first-day measurement (P<0.05). HF% levels significantly
      decreased the prematch day and the match day (P<0.05); however, no significant
      changes in LF/HF% ratio were observed. A gradual increase in VLF% and in LnVLF
      was observed, with a significant difference between first-day and match-day
      measurements (P<0.01 and P<0.05, respectively). The number of positive receptions
      was inversely correlated with LF/HFms(2) ratio, with LF/HF% ratio (R = -0.98,
      P<0.05 for both) and with resting HR (R = -0.92, P<0.05). CONCLUSIONS: Elite
      female athletes practising team sports exhibit a slight change in HRV prior to a
      decisive competition, without a pronounced variation of the autonomic nervous
      system activity. A day-to-day HRV measurement could be a useful tool to evaluate
      the impact of a competition on the autonomic nervous system in athletes, also
      considering the relationship between sympathetic activity and athletic
      performance.

PMID- 24112388
TI  - Epithelial-to-mesenchymal transition is involved in BCNU resistance in human
      glioma cells.
AB  - Chemotherapy has been considered as an effective treatment for malignant glioma;
      however, it becomes increasingly ineffective with tumor progression. Epithelial
      to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic
      and molecular alterations that facilitate tumor metastasis and progression.
      Emerging evidence associates chemoresistance with the acquisition of EMT in
      cancer. However, it is not clear whether this phenomenon is involved in glioma.
      We used the previously established human glioma cell lines SWOZ1, SWOZ2 and SWOZ2
      BCNU to assess cellular morphology, molecular changes, migration and invasion. We
      found that BCNU-resistant cells showed multiple drug resistance and phenotypic
      changes consistent with EMT, including spindle-shaped morphology and enhanced
      pseudopodia formation. Decreased expression of the epithelial adhesion molecule E
      cadherin and increased expression of the mesenchymal marker vimentin were
      observed in BCNU-resistant SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells.
      Migratory and metastatic potentials were markedly enhanced in SWOZ1 and SWOZ2
      BCNU cells compared to SWOZ2 cells. These data suggest that there is a possible
      link between drug resistance and EMT induction in glioma cells. Gaining further
      insight into the mechanisms underlying chemoresistance and EMT may enable the
      restoration of chemosensitivity or suppression of metastasis. 

PMID- 24112390
TI  - The progression of small-follicle reserves in the ovaries of wild African
      elephants (Loxodonta africana) from puberty to reproductive senescence.
AB  - This study aimed to determine whether the follicle reserve in the ovary of the
      African elephant declines progressively after puberty and whether its depletion
      constrains the fertility of older females. Elephant ovaries were fixed in 4%
      neutral buffered formalin and small-follicle counts made using stereological
      protocols. Excepting a slight rise in small-follicle numbers between 16 and 25
      years of age, there was a trend for follicle numbers to fall from puberty to 70
      years. Reproductive status did not impact significantly on small-follicle numbers
      (P=0.31). The number of early primary follicles, initially higher in number than
      true primary follicles, fell from post-puberty to nil at 45 years of age. Six of
      the seven oldest animals in the study showed signs of recent ovarian activity in
      the form of antral follicles, corpora lutea or large corpora nigra. The four
      oldest elephants (mean age 69 years) had a median small-follicle count of 11,113.
      In summary, it appears that the elephant ovary is capable of supplying oocytes
      for ovulation right up to the time of death at the age of maximum life
      expectancy, although the follicle reserve becomes depleted in some older
      elephants.

PMID- 24112391
TI  - Advances in metabolism.

PMID- 24112389
TI  - Role of Abl in airway hyperresponsiveness and airway remodeling.
AB  - BACKGROUND: Asthma is a chronic disease that is characterized by airway
      hyperresponsiveness and airway remodeling. The underlying mechanisms that mediate
      the pathological processes are not fully understood. Abl is a non-receptor
      protein tyrosine kinase that has a role in the regulation of smooth muscle
      contraction and smooth muscle cell proliferation in vitro. The role of Abl in
      airway hyperresponsiveness and airway remodeling in vivo is largely unknown.
      METHODS: To evaluate the role of Abl in asthma pathology, we assessed the
      expression of Abl in airway tissues from the ovalbumin sensitized and challenged
      mouse model, and human asthmatic airway smooth muscle cells. In addition, we
      generated conditional knockout mice in which Abl expression in smooth muscle was
      disrupted, and then evaluated the effects of Abl conditional knockout on airway
      resistance, smooth muscle mass, cell proliferation, IL-13 and CCL2 in the mouse
      model of asthma. Furthermore, we determined the effects of the Abl
      pharmacological inhibitors imatinib and GNF-5 on these processes in the animal
      model of asthma. RESULTS: The expression of Abl was upregulated in airway tissues
      of the animal model of asthma and in airway smooth muscle cells of patients with
      severe asthma. Conditional knockout of Abl attenuated airway resistance, smooth
      muscle mass and staining of proliferating cell nuclear antigen in the airway of
      mice sensitized and challenged with ovalbumin. Interestingly, conditional
      knockout of Abl did not affect the levels of IL-13 and CCL2 in bronchoalveolar
      lavage fluid of animals treated with ovalbumin. However, treatment with imatinib
      and GNF-5 inhibited the ovalbumin-induced increase in IL-13 and CCL2 as well as
      airway resistance and smooth muscle growth in animals. CONCLUSIONS: These results
      suggest that the altered expression of Abl in airway smooth muscle may play a
      critical role in the development of airway hyperresponsiveness and airway
      remodeling in asthma. Our findings support the concept that Abl may be a novel
      target for the development of new therapy to treat asthma.

PMID- 24112392
TI  - BRAF mutation is associated with distinct clinicopathological characteristics in
      colorectal cancer: a systematic review and meta-analysis.
AB  - AIM: Colorectal cancer is a heterogeneous disease with multiple underlying
      genetic mutations resulting in different phenotypes. Mutation in the v-Raf murine
      sarcoma viral oncogene homolog B1 (BRAF) proto-oncogene is an important event in
      the methylator pathway. There is no consensus, however, on the
      clinicopathological characteristics associated with BRAF mutation. METHOD: A
      comprehensive search for published studies examining the effect of BRAF mutation
      on colorectal cancer was performed. Random effects methods were used to combine
      data. RESULTS: Data were retrieved from 21 studies describing 9885 patients. BRAF
      associated colorectal cancer is associated with proximal tumour location (OR
      5.222, 95% CI 3.801-7.174, P < 0.001), T4 tumours (OR 1.761, 95% CI 1.164-2.663,
      P = 0.007) and poor differentiation (OR 3.816, 95% CI 2.714-5.365, P < 0.001) and
      is negatively associated with male sex (OR 0.623, 95% CI 0.505-0.769, P < 0.001),
      age of diagnosis under 60 years (OR 0.453, 95% CI 0.280-0.733, P = 0.001) and
      rectal cancer (OR 0.266, 95% CI 0.122-0.422, P < 0.001). CONCLUSION: BRAF
      mutation appears to be associated with distinct, unfavourable clinicopathological
      characteristics in colorectal cancer.

PMID- 24112393
TI  - Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa?
AB  - The true incidence of diabetic ketoacidosis (DKA) in sub-Saharan Africa is
      unknown but unlike in the Western countries, DKA is also uniquely frequent among
      type 2 diabetes patients of African origin. Increased hyperglycaemia and hepatic
      ketogenesis lead to osmotic diuresis, dehydration and tissue hypoxia. Acute
      complications of DKA include cerebral oedema, which may be compounded by
      malnutrition, parasitic and microbial infections with rampant tuberculosis and
      HIV. Overlapping symptoms of these conditions and misdiagnosis of DKA contribute
      to increased morbidity and mortality. Inability of the patients to afford insulin
      treatment leads to poor glycemic control as some patients seek alternative
      treatment from traditional healers or use herbal remedies further complicating
      the disease process. Standard treatment guidelines for DKA currently used may not
      be ideal as they are adapted from those of the developed world. Children
      presenting with suspected DKA should be screened for comorbidities which may
      complicate fluid and electrolyte replacement therapy protocol. Patient
      rehabilitation should take into account concurrent treatment for infectious
      conditions to avoid possible life-threatening drug interactions. We recommend
      that health systems in sub-Saharan Africa leverage the Expanded Immunization
      Programme or TB/HIV/AIDS programmes, which are fairly well entrenched to support
      diabetes services. 

PMID- 24112394
TI  - Mitochondrial reactive oxygen species as a mystery voice in hepatitis C.
AB  - There are several lines of evidence suggesting that oxidative stress is present
      in hepatitis C to a greater degree than in other inflammatory liver diseases and
      is closely related to disease progression. The main production site of reactive
      oxygen species (ROS) is assumed to be mitochondria, which concept is supported by
      evidence that hepatitis C virus (HCV) core protein is directly associated with
      them. The detoxification of ROS also is an important function of the cellular
      redox homeostasis system. These results draw our attention to how HCV-induced
      mitochondrial ROS production is beyond redox regulation and affects the disease
      progression and development of hepatocellular carcinoma (HCC) in chronic
      hepatitis C. On the other hand, HCV-related chronic liver diseases are
      characterized by metabolic alterations such as insulin resistance, hepatic
      steatosis and/or iron accumulation in the liver. These metabolic disorders also
      are relevant to the development of HCC in HCV-related chronic liver diseases.
      Here, we review the mechanisms by which HCV increases mitochondrial ROS
      production and offer new insights as to how mitochondrial ROS are linked to
      metabolic disorders such as insulin resistance, hepatic steatosis and hepatic
      iron accumulation that are observed in HCV-related chronic liver diseases. 

PMID- 24112395
TI  - A massive calcification and ossification of the transverse sinus and the
      neighbouring dura mimicking meningioma.
AB  - BACKGROUND: Although small calcifications of the dura and the transverse sinus
      occur frequently, large, single intracranial calcifications originating from the
      transverse sinus and the neighbouring dura are rare. CASE PRESENTATION: A 47-year
      old man was admitted to the hospital for a right occipital headache that had
      persisted for two weeks. There was no neurological deficit. Normal skull X-ray
      and computed tomography (CT) scans revealed an irregular, calcified, intracranial
      lesion of approximately 4.4 * 4.0 * 2.5 cm in volume in the right occipital
      region. Via surgery, a bone-hard, poorly vascularised, pink mass originating from
      the right transverse sinus and the convex dura of the right cerebellar
      hemisphere, as well as the cerebellar tentorium, was completely removed.
      Pathological examination yielded a diagnosis of fibrous connective tissue with
      hyaline degeneration, calcification and ossification with no indication of
      neoplasia or inflammation. CONCLUSIONS: We report a rare case of massive
      calcification and ossification of the transverse sinus and the neighbouring dura
      mimicking meningioma. Degenerative calcification and ossification may serve as a
      rare differential diagnosis of diseases, such as meningiomas, in the transverse
      sinus and the neighbouring dura.

PMID- 24112396
TI  - Acute functional decline before hospitalization in older patients.
AB  - AIMS: Acute diseases and related hospitalization are crucial events in the
      disabling process of elderly individuals. Most of the functional decline occurs
      in the few days before hospitalization, as a result of acute diseases in
      vulnerable patients. The aim of the present study was to identify determinants of
      prehospital components of functional decline. METHODS: This was a prospective
      observational study carried out in three acute geriatric units and two general
      medicine units of three Italian hospitals. The participants were 1281 patients
      aged 65 years or older admitted to hospital for acute illnesses and discharged
      alive. Functional status 2 weeks before hospitalization (preadmission) and at
      hospital admission was measured by the Barthel Index to identify patients with
      prehospital decline. In this group of decliners, the percentage extent of
      prehospital decline (PEPD) was also calculated. RESULTS: Prehospital decline
      occurred in 541 (42.2%) patients, who were hospitalized mostly in geriatric wards
      (55.6%). Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.04-1.08)
      and dementia (OR 2.8, 95% CI 1.4-5.4) were significant predictors of prehospital
      decline, whereas a high preadmission function was protective (OR 0.992, 95% CI
      0.987-0.997). Pulmonary disease as primary discharge diagnosis was also
      associated with prehospital decline (OR 1.8, 95% CI 1.3-2.5) after adjustment for
      age, diagnosis of dementia and preadmission function. Amongst decliners, a low
      preadmission function and the origin of patients (from emergency rooms or other
      hospital units) were associated with larger PEPD. CONCLUSIONS: Using a clinically
      meaningful change to define decline, disease-related prehospital disability is
      observed mainly in persons with low preadmission function, older age and
      dementia.

PMID- 24112398
TI  - Repair of a lateral neck defect using a trilobed transposition flap.

PMID- 24112397
TI  - Towards predicting the lung fibrogenic activity of nanomaterials: experimental
      validation of an in vitro fibroblast proliferation assay.
AB  - BACKGROUND: Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in
      rodents. Several studies have identified the capacity of CNT to stimulate the
      proliferation of fibroblasts. We developed and validated experimentally here a
      simple and rapid in vitro assay to evaluate the capacity of a nanomaterial to
      exert a direct pro-fibrotic effect on fibroblasts. METHODS: The activity of
      several multi-wall (MW)CNT samples (NM400, the crushed form of NM400 named
      NM400c, NM402 and MWCNTg 2400) and asbestos (crocidolite) was investigated in
      vitro and in vivo. The proliferative response to MWCNT was assessed on mouse
      primary lung fibroblasts, human fetal lung fibroblasts (HFL-1), mouse embryonic
      fibroblasts (BALB-3T3) and mouse lung fibroblasts (MLg) by using different assays
      (cell counting, WST-1 assay and propidium iodide PI staining) and dispersion
      media (fetal bovine serum, FBS and bovine serum albumin, BSA). C57BL/6 mice were
      pharyngeally aspirated with the same materials and lung fibrosis was assessed
      after 2 months by histopathology, quantification of total collagen lung content
      and pro-fibrotic cytokines in broncho-alveolar lavage fluid (BALF). RESULTS:
      MWCNT (NM400 and NM402) directly stimulated fibroblast proliferation in vitro in
      a dose-dependent manner and induced lung fibrosis in vivo. NM400 stimulated the
      proliferation of all tested fibroblast types, independently of FBS- or BSA-
      dispersion. Results obtained by WST1 cell activity were confirmed with cell
      counting and cell cycle (PI staining) assays. Crocidolite also stimulated
      fibroblast proliferation and induced pulmonary fibrosis, although to a lesser
      extent than NM400 and NM402. In contrast, shorter CNT (NM400c and MWCNTg 2400)
      did not induce any fibroblast proliferation or collagen accumulation in vivo,
      supporting the idea that CNT structure is an important parameter for inducing
      lung fibrosis. CONCLUSIONS: In this study, an optimized proliferation assay using
      BSA as a dispersant, MLg cells as targets and an adaptation of WST-1 as readout
      was developed. The activity of MWCNT in this test strongly reflects their
      fibrotic activity in vivo, supporting the predictive value of this in vitro assay
      in terms of lung fibrosis potential.

PMID- 24112399
TI  - [Refractory chronic erythema nodosum treated with adalimumab].

PMID- 24112400
TI  - Randomized, controlled trial of budesonide and prednisone for the treatment of
      idiopathic inflammatory bowel disease in dogs.
AB  - BACKGROUND: Budesonide has been used to treat inflammatory bowel disease (IBD) in
      dogs, but no controlled studies have been performed to evaluate efficacy of this
      treatment. OBJECTIVE: To compare budesonide and prednisone for induction therapy
      of IBD in dogs by using IBD activity index scores and evaluating frequency and
      severity of owner-reported adverse effects. ANIMALS: Forty client-owned dogs with
      newly diagnosed idiopathic IBD were enrolled between April 2001 and January 2004;
      34 dogs completed the 6 week study. METHODS: Double-blinded, randomized
      controlled trial. Dogs were randomized to receive either pure powder-based
      budesonide (3-7 kg: 1 mg PO q24h, 7.1-15 kg: 2 mg PO q24h, 15.1-30 kg: 3 mg PO
      q24h, >30 kg: 5 mg PO q24h) for 6 weeks or prednisone (1 mg/kg PO q12h * 3 weeks
      then 0.5 mg/kg PO q12h * 3 weeks). IBD activity index (IBDAI) scores were
      determined at diagnosis and after 6 weeks of treatment. Pet owners completed
      weekly questionnaires regarding clinical signs and incidence and severity of
      adverse effects. RESULTS: Significant differences in remission rates (>75%
      decrease in IBDAI scores) were not observed with a remission rate of 78% in the
      budesonide group and 69% in the prednisone group (P = .70). Frequency of adverse
      effects was similar between the 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE:
      There was no demonstrable difference in remission rates or incidence of adverse
      effects between prednisone and budesonide for induction therapy of IBD in dogs.

PMID- 24112401
TI  - Baseline characteristics from an ongoing phase 3 study of collagenase clostridium
      histolyticum in patients with Peyronie's disease.
AB  - INTRODUCTION: Peyronie's disease (PD) is a localized penile collagen disorder of
      the tunica albuginea associated with significant physical deformity and
      psychological impairment. Current understanding of pretreatment characteristics
      in patients with chronic PD is limited by small samples, varied quality of
      assessments, and the lack of a PD-specific, validated measure of the psychosexual
      impact of PD. AIMS: Reporting baseline demographic and disease characteristics of
      the large multinational cohort of subjects with chronic PD who participated in
      the collagenase clostridium histolyticum (CCH, an investigational intralesional
      injection and minimally invasive intervention) phase 3 clinical study program.
      Findings from well-defined assessments, including the Peyronie's Disease
      Questionnaire (PDQ), the first validated PD-specific patient-reported measure of
      psychosexual impact, are reported. METHODS: Subjects included men>=18 years old
      with PD symptoms>=12 months and penile deformity between 30 degrees  and 90
      degrees . Analysis data included demographics, disease history, and psychosexual
      impact. MAIN OUTCOME MEASURES: Penile deformity, disease symptoms, the
      International Index of Erectile Function, and the PDQ were assessed. RESULTS:
      Eight hundred thirty-two subjects were enrolled from 64 sites across the United
      States and Australia. The mean age was 57.7 years; mean PD duration was 4.1
      years. The majority of subjects had penile deformity<=60 degrees  (77.3%); mean
      penile deformity was 50.5 degrees . Subjects reported having intercourse a mean
      of 10.2 times in the previous 3 months, 70.8% reported difficulty in performing
      vaginal intercourse, and 80.4% reported less frequent vaginal intercourse.
      Approximately 71.5% of subjects with severe (>60 degrees ) and 58.1% of subjects
      with mild/moderate (<=60 degrees ) penile deformity were "very bothered" or
      "extremely bothered" upon last look at their erect penis (P=0.0041), as measured
      by the PDQ. CONCLUSIONS: These data add to the body of knowledge regarding the
      clinical impact of chronic phase PD, including the PD-specific patient-reported
      psychosexual symptoms, using a large multinational chronic PD cohort in the CCH
      phase 3 clinical program.

PMID- 24112402
TI  - High frequency of intrathecal immunoglobulin synthesis in epilepsy so far
      classified cryptogenic.
AB  - BACKGROUND AND PURPOSE: The influence of the immune system on seizures and
      epileptogenesis has been increasingly considered, in particular the role of
      autoantibodies. In this study, we aimed to determine the frequency of intrathecal
      antibody synthesis in the cerebrospinal fluid (CSF) compartment of patients with
      epilepsy. METHODS: In a retrospective cohort study trial in a university hospital
      neurology department, 164 well-characterized patients with different etiologies
      of seizures and epilepsies, and 77 control patients were included. RESULTS: CSF
      specific immunoglobulin (IgG, IgM and IgA) synthesis was significantly (P <
      0.0001) more frequent in patients with epilepsy (34.1%) compared with age- and
      sex-matched controls (2.6%). The highest incidence of intrathecal Ig synthesis
      was detected in patients with encephalitis-related acute symptomatic seizures
      (86.7%), but also in patients with focal epilepsy so far classified cryptogenic
      (45.2%). Antibody synthesis was not related to the number of CSF white blood
      cells. CONCLUSIONS: Humoral immune activation in the CSF compartment was detected
      in one-third of patients with epilepsy, besides acute symptomatic seizures
      particularly frequent in cryptogenic epilepsy--an etiology so far defined as not
      having a detectable cause. Systematic prospective clinical and experimental
      trials are required to identify antigenic targets and select appropriate patients
      for which immunotherapy might offer new causal therapeutic options.

PMID- 24112403
TI  - Evidence-based health information from the users' perspective--a qualitative
      analysis.
AB  - BACKGROUND: Evidence-based information is a precondition for informed decision
      making and participation in health. There are several recommendations and
      definitions available on the generation and assessment of so called evidence
      based health information for patients and consumers (EBHI). They stress the
      importance of objectively informing people about benefits and harms and any
      uncertainties in health-related procedures. There are also studies on the
      comprehensibility, relevance and user-friendliness of these informational
      materials. But to date there has been little research on the perceptions and
      cognitive reactions of users or lay people towards EBHI. The aim of our study is
      to define the spectrum of consumers' reaction patterns to written EBHI in order
      to gain a deeper understanding of their comprehension and assumptions, as well as
      their informational needs and expectations. METHODS: This study is based on an
      external user evaluation of EBHI produced by the German Institute for Quality and
      Efficiency in Health Care (IQWiG), commissioned by the IQWiG. The EBHI were
      examined within guided group discussions, carried out with lay people. The test
      readers' first impressions and their appraisal of the informational content,
      presentation, structure, comprehensibility and effect were gathered. Then a
      qualitative text analysis of 25 discussion transcripts involving 94 test readers
      was performed. RESULTS: Based on the qualitative text analysis a framework for
      reaction patterns was developed, comprising eight main categories: (i) interest,
      (ii) satisfaction, (iii) reassurance and trust, (iv) activation, (v) disinterest,
      (vi) dissatisfaction and disappointment, (vii) anxiety and worry, (viii) doubt.
      CONCLUSIONS: Many lay people are unfamiliar with core characteristics of this
      special information type. Two particularly critical issues are the description of
      insufficient evidence and the attendant absence of clear-cut recommendations.
      Further research is needed to examine strategies to explain the specific
      character of EBHI so as to minimize unintended or adverse reaction patterns. The
      presented framework describes the spectrum of users' reaction patterns to EBHI.
      It may support existing best practice models for editing EBHI.

PMID- 24112404
TI  - Immunoassays of fungal laccases for screening of natural enzymes and control of
      recombinant enzyme production.
AB  - Because of the wide application of laccases in different biotechnological
      processes and intense studies of the enzymes from different sources, the
      development of efficient techniques for monitoring laccase level is a task of
      significant importance. Enzyme-linked immunosorbent assay (ELISA) and Western
      blotting techniques were developed to control total content and isoform
      composition of laccases, including their recombinant preparations. Because
      glycosylated and nonglycosylated forms have different structures and sets of
      epitopes, two kinds of polyclonal antibodies were obtained and applied. The first
      antibody recognized the native (glycosylated) laccase purified from Trametes
      hirsuta and the second one reacted with recombinant (nonglycosylated) laccase
      expressed in Escherichia coli. Titers of the antibodies were analyzed by indirect
      ELISA with laccases isolated from several strains of basidiomycetes. The obtained
      cross-reactivity data for both antibodies demonstrated a correspondence with
      sequence homology of the laccases. The antibodies raised against recombinant
      (nonglycosylated) laccase had higher titers and thus were preferable for
      screening of recombinant laccase in cultural media. Thus, optimal antibody
      preparations were selected for screening of laccase-producing strains, and the
      control of recombinant enzymes and the efficiency of their use in immunochemical
      control of laccase levels were confirmed. 

PMID- 24112405
TI  - Predictive value of specific IgE for clinical peanut allergy in children:
      relationship with eczema, asthma, and setting (primary or secondary care).
AB  - The usefulness of peanut specific IgE levels for diagnosing peanut allergy has
      not been studied in primary and secondary care where most cases of suspected
      peanut allergy are being evaluated. We aimed to determine the relationship
      between peanut-specific IgE levels and clinical peanut allergy in peanut
      sensitized children and how this was influenced by eczema, asthma and clinical
      setting (primary or secondary care). We enrolled 280 children (0-18 years) who
      tested positive for peanut-specific IgE (> 0.35 kU/L) requested by primary and
      secondary physicians. We used predefined criteria to classify participants into
      three groups: peanut allergy, no peanut allergy, or possible peanut allergy,
      based on responses to a validated questionnaire, a detailed food history, and
      results of oral food challenges.Fifty-two participants (18.6%) were classified as
      peanut allergy, 190 (67.9%) as no peanut allergy, and 38 (13.6%) as possible
      peanut allergy. The association between peanut-specific IgE levels and peanut
      allergy was significant but weak (OR 1.46 for a 10.0 kU/L increase in peanut
      specific IgE, 95% CI 1.28-1.67). Eczema was the strongest risk factor for peanut
      allergy (aOR 3.33, 95% CI 1.07-10.35), adjusted for demographic and clinical
      characteristics. Asthma was not significantly related to peanut allergy (aOR
      1.93, 95% CI 0.90-4.13). Peanut allergy was less likely in primary than in
      secondary care participants (OR 0.46, 95% CI 0.25-0.86), at all levels of peanut
      specific IgE.The relationship between peanut-specific IgE and peanut allergy in
      children is weak, is strongly dependent on eczema, and is weaker in primary
      compared to secondary care. This limits the usefulness of peanut-specific IgE
      levels in the diagnosis of peanut allergy in children. 

PMID- 24112407
TI  - Lenalidomide-induced photosensitivity.

PMID- 24112406
TI  - Lipid exposure prediction enhances the inference of rotational angles of
      transmembrane helices.
AB  - BACKGROUND: Since membrane protein structures are challenging to crystallize,
      computational approaches are essential for elucidating the sequence-to-structure
      relationships. Structural modeling of membrane proteins requires a
      multidimensional approach, and one critical geometric parameter is the rotational
      angle of transmembrane helices. Rotational angles of transmembrane helices are
      characterized by their folded structures and could be inferred by the hydrophobic
      moment; however, the folding mechanism of membrane proteins is not yet fully
      understood. The rotational angle of a transmembrane helix is related to the
      exposed surface of a transmembrane helix, since lipid exposure gives the degree
      of accessibility of each residue in lipid environment. To the best of our
      knowledge, there have been few advances in investigating whether an environment
      descriptor of lipid exposure could infer a geometric parameter of rotational
      angle. RESULTS: Here, we present an analysis of the relationship between
      rotational angles and lipid exposure and a support-vector-machine method, called
      TMexpo, for predicting both structural features from sequences. First, we
      observed from the development set of 89 protein chains that the lipid exposure,
      i.e., the relative accessible surface area (rASA) of residues in the lipid
      environment, generated from high-resolution protein structures could infer the
      rotational angles with a mean absolute angular error (MAAE) of 46.32. More
      importantly, the predicted rASA from TMexpo achieved an MAAE of 51.05, which is
      better than 71.47 obtained by the best of the compared hydrophobicity scales.
      Lastly, TMexpo outperformed the compared methods in rASA prediction on the
      independent test set of 21 protein chains and achieved an overall Matthew's
      correlation coefficient, accuracy, sensitivity, specificity, and precision of
      0.51, 75.26%, 81.30%, 69.15%, and 72.73%, respectively. TMexpo is publicly
      available at http://bio-cluster.iis.sinica.edu.tw/TMexpo. CONCLUSIONS: TMexpo can
      better predict rASA and rotational angles than the compared methods. When
      rotational angles can be accurately predicted, free modeling of transmembrane
      protein structures in turn may benefit from a reduced complexity in ensembles
      with a significantly less number of packing arrangements. Furthermore, sequence
      based prediction of both rotational angle and lipid exposure can provide
      essential information when high-resolution structures are unavailable and
      contribute to experimental design to elucidate transmembrane protein functions.

PMID- 24112408
TI  - Immunohistochemical localization of spatacsin in alpha-synucleinopathies.
AB  - Spatacsin (SPG11) is a major mutated gene in autosomal recessive spastic
      paraplegia with thin corpus callosum (ARHSP-TCC) and is responsible for juvenile
      Parkinsonism. To elucidate the role of spatacsin in the pathogenesis of alpha
      synucleinopathies, an immunohistochemical investigation was performed on the
      brain of patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB)
      and multiple system atrophy (MSA) using anti-spatacsin antibody. In PD, Lewy
      bodies (LBs) in the brain stem were positive for spatacsin. These LBs showed
      intense staining in their peripheral portions and occasionally in the central
      cores. Lewy neurites were also spatacsin-positive. In DLB, cortical LBs were
      immunolabeled by spatacsin. In MSA, glial cytoplasmic inclusions (GCI) and a
      small fraction of neuronal cytoplasmic inclusions (NCI) were positive for
      spatacsin. The widespread accumulation of spatacsin observed in pathologic alpha
      synuclein-containing inclusions suggests that spatacsin may be involved in the
      pathogenesis of alpha-synucleinopathies. 

PMID- 24112409
TI  - Towards a unified paradigm for sequence-based identification of fungi.
AB  - The nuclear ribosomal internal transcribed spacer (ITS) region is the formal
      fungal barcode and in most cases the marker of choice for the exploration of
      fungal diversity in environmental samples. Two problems are particularly acute in
      the pursuit of satisfactory taxonomic assignment of newly generated ITS
      sequences: (i) the lack of an inclusive, reliable public reference data set and
      (ii) the lack of means to refer to fungal species, for which no Latin name is
      available in a standardized stable way. Here, we report on progress in these
      regards through further development of the UNITE database (http://unite.ut.ee)
      for molecular identification of fungi. All fungal species represented by at least
      two ITS sequences in the international nucleotide sequence databases are now
      given a unique, stable name of the accession number type (e.g. Hymenoscyphus
      pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological
      annotations were corrected as far as possible through a distributed, third-party
      annotation effort. We introduce the term 'species hypothesis' (SH) for the taxa
      discovered in clustering on different similarity thresholds (97-99%). An
      automatically or manually designated sequence is chosen to represent each such
      SH. These reference sequences are released (http://unite.ut.ee/repository.php)
      for use by the scientific community in, for example, local sequence similarity
      searches and in the QIIME pipeline. The system and the data will be updated
      automatically as the number of public fungal ITS sequences grows. We invite
      everybody in the position to improve the annotation or metadata associated with
      their particular fungal lineages of expertise to do so through the new Web-based
      sequence management system in UNITE. 

PMID- 24112410
TI  - The rare case of Alternaria alternata cutaneous and pulmonary infection in a
      heart transplant recipient treated by azole antifungals.
AB  - We report a case of Alternaria alternata cutaneous and pulmonary infection in a
      62-year-old man after heart transplantation treated by azole antifungals.
      Alternaria spp. belong to a group of opportunistic dematiaceous fungi with
      worldwide distribution. The cutaneous form of the infection in human is very rare
      and occurs predominantly among immunosuppressed patients. Therefore, diagnosis is
      often delayed or not reached at all. Appropriate treatment is not standardized
      and remains a matter of discussion. According to current studies, the best
      results are obtained with systemic azole antifungal therapy combined with
      surgical intervention. 

PMID- 24112411
TI  - Diabetes mellitus and tuberculosis: pattern of tuberculosis, two-month smear
      conversion and treatment outcomes in Guangzhou, China.
AB  - OBJECTIVE: There is a high burden of both diabetes (DM) and tuberculosis (TB) in
      China. We evaluated the association between DM and the pattern of disease, 2
      month sputum smear conversion and treatment outcomes of patients with TB in
      Guangzhou, China. METHOD: All patients registered with TB from September 2011 to
      June 2012 were screened for DM and assessed for treatment outcomes in relation to
      presence or absence of DM and quality of DM control using patient registers,
      treatment cards and electronic record systems. RESULTS: There were 1589 patients
      with TB of whom 189 (12%) had DM. Among those with DM, there was a significantly
      higher proportion of men, persons aged 35 years and older and persons with smear
      positive pulmonary tuberculosis (PTB) (P < 0.01). In patients with DM and new
      smear-positive PTB, there was a higher proportion who had positive sputum smears
      at 2 months (21.7% vs. 5.6%, RR 3.85, 95%CI 2.24-6.63), who were lost-to-follow
      up (5.2% vs. 1.7%, RR 3.23, 95%CI 1.08-9.63) and who failed treatment (10.3% vs.
      2.3%, RR 4.46, 95%CI 1.96-10.18) compared with patients who had no DM. There was
      no significant association between these adverse outcomes and DM control as
      measured by 2 and 6-month fasting blood glucose. CONCLUSION: Diabetes mellitus in
      new smear-positive patients with PTB was associated with failure to sputum smear
      convert at 2 months and adverse treatment outcomes of loss-to-follow-up and
      failure. Further research is needed to understand the reasons for these findings
      and to determine whether the current length of treatment of 6 months is adequate.

PMID- 24112412
TI  - Indocyanine green plasma disappearance rate: a new tool for the classification of
      paediatric patients with acute liver failure.
AB  - BACKGROUND & AIMS: Pediatric acute liver failure is a rare disorder which results
      in death or the need for liver transplantation in 25-50% of cases. The adults
      scores are unable to predict survival without liver transplantation of pediatric
      patients. The present study assessed the use the of indocyanine green plasma
      disappearance rate as a tool to predict the evolution of pediatric patients with
      acute liver failure. PATIENTS AND METHODS: All patients met the criteria of acute
      liver failure according to the Pediatric Acute Liver Failure Study Group. King's
      College, Clichy's criteria and ICG-PDR were obtained on admission or when acute
      liver failure was diagnosed and repeated every 12-24 hours, respectively.
      RESULTS: Thirteen out of 48 patients suffered an irreversible liver damage. Seven
      of them underwent a liver transplantation and 6 died on the waiting. A total of
      154 ICG-PDR measurements were taken during the study (Median 12.4 %/min, r:6.2 -
      26.3). The ICG-PDR was significantly lower in patients who suffered irreversible
      liver damage compared with those who survived without liver transplantation
      (median ICG-PDR 4.1 %/min; r:4.0 - 5.7 vs median ICG-PDR 20.3 %/min; r: 9.1 -
      30.1; respectively. P < 0.001). Using a ROC curve the cutoff of ICG-PDR for
      assessing the need for liver transplantation was set at 5.9 %/min (sensitivity
      92.3%, specificity 97.1%). Sensitivity, specificity, PPV, NPV and DA for ICG-PDR
      were higher than the King's College and Clichy's criteria. CONCLUSIONS: ICG-PDR
      is a powerful tool that would improve the categorization of patients with
      pediatric acute liver failure.

PMID- 24112413
TI  - Prognostic significance of epidermal growth factor receptor overexpression in
      pancreas cancer and nodal metastasis.
AB  - BACKGROUND: Identification of molecular markers in pancreatic adenocarcinoma (PA)
      has the potential to guide targeted therapy. The objective of this study is to
      determine the prognostic significance of epidermal growth factor receptor (EGFR)
      expression (membrane and cytoplasmic) in resected PA and its correlation with
      lymph node metastasis and survival. METHODS: EGFR overexpression was determined
      by immunohistochemistry, and the pattern of expression was compared between the
      primary tumour, adjacent normal pancreas and involved lymph nodes. RESULTS: A
      total of 88 patients had curative resection. No difference was found in mEGFR
      overexpression between tumoural and metastatic nodal tissues (P = 0.28). Median
      overall survival time was 22.9 months. Overall cumulative 1-, 3- and 5-year
      survival was 48%, 20% and 18%, respectively. In positive mEGFR tumour expression,
      survival was 46% at 1 year, 8% at 3 years and 0% at 5 years (P < 0.05).
      Univariate analysis showed that male gender, portal vein (PV) resection,
      perineural, lymphovascular and peri-pancreatic invasion, positive margins and
      positive mEGFR expression in tumour tissue had worse survival. Multivariate
      analysis showed that male gender, PV resection, vascular and perineural invasion
      remained independent predictors of poor survival. CONCLUSION: Positive mEGFR
      overexpression is associated with decreased survival; however, it is not an
      independent prognostic factor.

PMID- 24112414
TI  - The vagina dialogues: genital self-image and communication with physicians about
      sexual dysfunction and dissatisfaction among Jewish patients in a women's health
      clinic in southern Israel.
AB  - INTRODUCTION: The health-care system offers a variety of solutions for problems
      related to sexual dysfunction. To gain access to treatment options, women must be
      willing to discuss these issues with their physicians. AIM: To examine the extent
      to which women discuss issues of sexual dysfunction with their physicians and to
      examine the contribution of aspects of sexual dysfunction, level of satisfaction,
      body image, and genital self-image to their comfort with communicating with
      physicians about these issues. METHODS: One hundred ten secular-appearing, Hebrew
      speaking Jewish women waiting for a routine gynecological appointment at a clinic
      in southern Israel responded to a self-report questionnaire. MAIN OUTCOME
      MEASURES: The Female Sexuality Function Index was used to assess sexual
      dysfunction, Gray's Modified Questionnaire to assess body image, and the Genital
      Self-Image Scale to assess genital self-image. We compiled a new measure to
      assess level of comfort in discussing sexual functioning and satisfaction with a
      physician. RESULTS: Forty-four percent of the women had discussed sexual
      functioning issues with a gynecologist. Of those, 91.7% reported that the
      gynecologist initiated the discussion. The proportion of participants who would
      consult a gynecologist about sexual dysfunction was 74.5%, but only 41% would
      consult a family physician. Half of the women would expect a gynecologist to
      initiate such consultations, but only 20% would expect a family physician to do
      so. In a multivariate regression analysis, genital self-image was the only
      significant predictor of women's comfort level with discussing sexual dysfunction
      with a gynecologist. CONCLUSIONS: The respondents perceived the gynecologist,
      rather than the family physician, as an appropriate professional to consult
      regarding sexual dysfunction. However, they expected the gynecologist to initiate
      the discussion. Women with a positive genital self-image are more comfortable in
      consulting about sexual dysfunction. Gynecologists should be made aware of their
      significant role in eliciting women's cooperation in such consultations and in
      contributing to improving women's genital perception.

PMID- 24112415
TI  - In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of
      famciclovir and its metabolites.
AB  - OBJECTIVES: To assess in vitro the antiviral efficacy against feline herpesvirus
      (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its
      metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of
      penciclovir application on in vitro antiviral activity. PROCEDURES: Plaque
      reduction assays were used to estimate antiviral efficacy of all compounds and
      the effect of penciclovir exposure before or after exposure to a FHV-1 field
      isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell
      number for 72 h following exposure to each compound. RESULTS: The penciclovir
      concentration that inhibited FHV-1-induced plaque formation by 50% (IC50 ) was
      0.86 MUg/mL (3.4 MUm). Famciclovir and BRL 42359 had no antiviral effect against
      FHV-1 at any concentration assessed. Antiviral activity was significantly
      enhanced when cells were exposed to 4 MUm penciclovir (approximate IC50 ) for 1 h
      but not for 24 h before viral adsorption. Delaying exposure of cells to
      penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced
      antiviral activity. Relative to untreated control wells, >88% of cells remained
      viable when exposed to famciclovir (100 MUm), BRL 42359 (1.06 mm), or penciclovir
      (40 MUm) for 72 h. No morphologic evidence of cytotoxicity was noted.
      CONCLUSIONS: Penciclovir demonstrates potent antiviral activity against FHV-1 and
      may be effective at lower tissue, tear, and plasma concentrations than previously
      targeted. The duration of in vitro antiviral effect of penciclovir suggests that
      frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL
      42359 showed no signs of in vitro cytotoxicity.

PMID- 24112416
TI  - The antibrowning agent sulfite inactivates Agaricus bisporus tyrosinase through
      covalent modification of the copper-B site.
AB  - Sulfite salts are widely used as antibrowning agents in food processing.
      Nevertheless, the exact mechanism by which sulfite prevents enzymatic browning
      has remained unknown. Here, we show that sodium hydrogen sulfite (NaHSO3)
      irreversibly blocks the active site of tyrosinase from the edible mushroom
      Agaricus bisporus, and that the competitive inhibitors tropolone and kojic acid
      protect the enzyme from NaHSO3 inactivation. LC-MS analysis of pepsin digests of
      NaHSO3 -treated tyrosinase revealed two peptides showing a neutral loss
      corresponding to the mass of SO3 upon MS(2) fragmentation. These peptides were
      found to be homologous peptides containing two of the three histidine residues
      that form the copper-B-binding site of mushroom tyrosinase isoform PPO3 and
      mushroom tyrosinase isoform PPO4, which were both present in the tyrosinase
      preparation used. Peptides showing this neutral loss behavior were not found in
      the untreated control. Comparison of the effects of NaHSO3 on apo-tyrosinase and
      holo-tyrosinase indicated that inactivation is facilitated by the active site
      copper ions. These data provide compelling evidence that inactivation of mushroom
      tyrosinase by NaHSO3 occurs through covalent modification of a single amino-acid
      residue, probably via addition of HSO3(-) to one of the copper-coordinating
      histidines in the copper-B site of the enzyme.

PMID- 24112418
TI  - Pseudocystic encapsulation: a late noninflammatory complication of hyaluronic
      acid filler injections.

PMID- 24112417
TI  - Rationale, design, and methodology for the optimizing outcomes in women with
      gestational diabetes mellitus and their infants study.
AB  - BACKGROUND: Women who are diagnosed with gestational diabetes mellitus (GDM) are
      at increased risk for developing prediabetes and type 2 diabetes mellitus (T2DM).
      To date, there have been few interdisciplinary interventions that target
      predominantly ethnic minority low-income women diagnosed with GDM. This paper
      describes the rationale, design and methodology of a 2-year, randomized,
      controlled study being conducted in North Carolina. METHODS/DESIGN: Using a two
      group, repeated measures, experimental design, we will test a 14- week intensive
      intervention on the benefits of breastfeeding, understanding gestational diabetes
      and risk of progression to prediabetes and T2DM, nutrition and exercise
      education, coping skills training, physical activity (Phase I), educational and
      motivational text messaging and 3 months of continued monthly contact (Phase II).
      A total of 100 African American, non-Hispanic white, and bilingual Hispanic women
      between 22-36 weeks of pregnancy who are diagnosed with GDM and their infants
      will be randomized to either the experimental group or the wait-listed control
      group. The first aim of the study is to determine the feasibility of the
      intervention. The second aim of study is to test the effects of the intervention
      on maternal outcomes from baseline (22-36 weeks pregnant) to 10 months
      postpartum. Primary maternal outcomes will include fasting blood glucose and
      weight (BMI) from baseline to 10 months postpartum. Secondary maternal outcomes
      will include clinical, adiposity, health behaviors and self-efficacy outcomes
      from baseline to 10 months postpartum. The third aim of the study is to quantify
      the effects of the intervention on infant feeding and growth. Infant outcomes
      will include weight status and breastfeeding from birth through 10 months of age.
      Data analysis will include general linear mixed-effects models. Safety endpoints
      include adverse event reporting. DISCUSSION: Findings from this trial may lead to
      an effective intervention to assist women diagnosed with GDM to improve maternal
      glucose homeostasis and weight as well as stabilize infant growth trajectory,
      reducing the burden of metabolic disease across two generations. TRIAL
      REGISTRATION: NCT01809431.

PMID- 24112420
TI  - Differences in health, productivity and quality of care in younger and older
      nurses.
AB  - AIM: To determine if younger and older hospital employed nurses have differences
      in their self-reported health, health related productivity and quality of care.
      BACKGROUND: An understanding of age cohort differences may assist nurse managers
      in understanding the health related productivity and potential quality of care
      concerns of their staff. METHOD: A cross-sectional survey design was utilised.
      There were 1171 usable surveys returned (47% response rate). Nurses over the age
      of 50 made up 26% of the respondents. RESULT: Older nurses had a higher body mass
      index (BMI), higher mental well-being, higher pain scores, a 12% higher
      prevalence of having health problems, and reported a higher health related
      productivity loss than younger nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers must determine if their older nurses are being given more difficult,
      complex patients because of their experience. Perhaps older nurses, especially
      those with health problems, need assignments that require their assessment and
      critical thinking skills rather than their strength and physical abilities.

PMID- 24112419
TI  - Feasibility intervention trial of two types of improved cookstoves in three
      resource-limited settings: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Exposure to biomass fuel smoke is one of the leading risk factors for
      disease burden worldwide. International campaigns are currently promoting the
      widespread adoption of improved cookstoves in resource-limited settings, yet
      little is known about the cultural and social barriers to successful improved
      cookstove adoption and how these barriers affect environmental exposures and
      health outcomes. DESIGN: We plan to conduct a one-year crossover, feasibility
      intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We
      will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total
      120 to 138). METHODS: At baseline, we will collect information on
      sociodemographic characteristics and cooking practices, and measure respiratory
      health and blood pressure for all participating women. An initial observational
      period of four months while households use their traditional, open-fire design
      cookstoves will take place prior to randomization. All participants will then be
      randomized to receive one of two types of improved, ventilated cookstoves with a
      chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a
      locally-constructed cookstove. After four months of observation, participants
      will crossover and receive the other improved cookstove design and be followed
      for another four months. During each of the three four-month study periods, we
      will collect monthly information on self-reported respiratory symptoms, cooking
      practices, compliance with cookstove use (intervention periods only), and measure
      peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon
      monoxide and blood pressure. We will also measure pulmonary function testing in
      the women participants and 24-hour kitchen particulate matter and carbon monoxide
      levels at least once per period. DISCUSSION: Findings from this study will help
      us better understand the behavioral, biological, and environmental changes that
      occur with a cookstove intervention. If this trial indicates that reducing indoor
      air pollution is feasible and effective in resource-limited settings like Peru,
      Kenya and Nepal, trials and programs to modify the open burning of biomass fuels
      by installation of low-cost ventilated cookstoves could significantly reduce the
      burden of illness and death worldwide. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01686867.

PMID- 24112423
TI  - Persistent allergy to cow's milk: of greater a clinical concern than other food
      allergies.

PMID- 24112421
TI  - CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik
      people.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified single
      nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly
      among individuals of European ancestry. In the present study, we examined the
      frequency of these SNPs and their association with T2D-related traits in an
      Alaska Native study population with a historically low prevalence of T2D. We also
      investigated whether dietary characteristics that may protect against T2D, such
      as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations.
      METHODS: In 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS
      for individual and cumulative associations with T2D-related traits. Cumulative
      associations were evaluated using a genetic risk score (GRS) calculated by
      summing risk alleles. Associations were tested for interactions with sex, body
      mass index (BMI), and n-3 PUFA intake. RESULTS: The rs7754840 SNP in CDKAL1 is
      significantly associated with HbA1c (P = 0.00091). The rs5015480 SNP near HHEX is
      significantly associated (in opposite direction to that in Europeans) with a
      combined fasting glucose (FG) and HbA1c measure (P = 0.00046) and with
      homeostatic model assessment of beta-cell function (HOMA-B; P = 0.0014). The GRS
      is significantly associated with FG and combined FG and HbA1c only when the HHEX
      SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA
      intake. CONCLUSION: Our results highlight the potential importance of CDKAL1 and
      HHEX in glucose homeostasis in this Alaska Native population with a low
      prevalence of T2D, and suggest that these loci should be examined in greater
      detail in this population.

PMID- 24112424
TI  - How to reintroduce cow's milk?
AB  - In a child that is allergic to milk, the natural next step, following the
      elimination diet, is the reintroduction of cow's milk. Several questions may
      arise. When feasible, this reintroduction has many benefits for the child and his
      family. However, the disease needs to be well defined by physicians and explained
      to parents. They need to understand that there are different types of allergy to
      cow's milk, specifically IgE- and non-IgE-mediated, and each of these may exhibit
      both a variable duration and frequently an incomplete recovery. Deciding where to
      first reintroduce cow's milk to a child who has previously followed a milk-free
      diet, whether it be at home or in a hospital, also frequently presents an issue.
      Following this first reintroduction, the progressive increase of milk into the
      diet needs to be managed properly, as not all children will go back to a normal
      dairy products intake. Recent studies show that most children with milk allergy
      tolerate products containing baked milk and that their consumption might speed up
      recovery. Hence, the purpose of the milk challenge in a child on a milk-free diet
      is becoming, even in a child still reactive to milk, the first step of gradual
      and individually adapted reintroduction of milk or dairy products. When
      reintroduction of cow's milk does not work, immunotherapy becomes an option, and
      this is carried out in specialized centers. 

PMID- 24112425
TI  - Immunotherapy - risk/benefit in food allergy.
AB  - Food allergy is a growing health concern in the westernized world with approx. 6%
      of children suffering from it. A lack of approved treatment has led to strict
      avoidance of the culprit food proteins being the only standard of care. Nowadays
      in-depth research is conducted to evaluate the possible use of allergen-specific
      immunotherapy (SIT) as an active therapeutic option for food allergy. Various
      routes of administration for the immunotherapy are investigated, including
      subcutaneous, oral, sublingual, and epicutaneous, and some appear to be
      successful in inducing a temporary tolerant state. Most research has been
      conducted with oral immunotherapy due to its efficacious and relatively safe
      profile. Increasing interest is dedicated to safer and more convenient
      approaches, such as sublingual and epicutaneous SIT; however, doubts exist about
      their possible capacity to induce temporary tolerant state and permanent oral
      tolerance. The high frequency of allergic adverse reactions of the various
      approaches and the inability to achieve permanent oral tolerance have highlighted
      the need of refinements in the strategies. A promising strategy for preventing
      IgE cross-linking and thus enhancing safety of SIT, while still activating T
      cells, is the use of tolerogenic peptides. The implementation of such an
      immunotherapy approach has the potential of not only increasing the chance of
      achieving a permanent state of tolerance, but also improving the safety and
      tolerability of the therapy. Immunotherapy for food allergy is still not ready
      for the clinic, but current and upcoming studies are dedicated to collect enough
      evidence for the possible implementation of allergen-SIT as a standard treatment
      for food allergy. 

PMID- 24112426
TI  - Food avoidance in children with adverse food reactions: influence of anxiety and
      clinical parameters.
AB  - BACKGROUND: Many children in the general population avoid food because of self
      reported adverse food reactions (AFR). Food avoidance can have negative
      consequences for well-being and nutritional status. This study aimed to
      investigate which factors are related to avoidance behavior in children (10-13 yr
      old) from the general population. METHODS: Questionnaires for both mother and
      child were sent to participants from the Europrevall study: 164 children with
      self-reported AFR and 170 children without AFRs. Spielberger state anxiety and
      trait anxiety and clinical parameters, such as severity of the adverse reaction,
      specific IgE and doctor's diagnosis, were compared between those who have (had)
      AFR and avoid food (i.e., avoiders) and those who have (had) AFR(s) and do not
      avoid food (anymore; i.e., non-avoiders). RESULTS: In total, 59% of the children
      with AFRs avoided food, of whom 26% had positive specific immunoglobulin E
      (sIgE). Child's state anxiety about an AFR was higher in avoiders than in non
      avoiders, (p < 0.001), whereas child's trait anxiety and maternal state anxiety
      and trait anxiety were comparable in both groups. Avoiders reported more often
      severe symptoms (i.e., generalized urticaria, respiratory or cardiovascular
      symptoms) than non-avoiders, (p = 0.03). Food avoidance was not associated with
      doctor's diagnosis of food allergy or doctor's advice to avoid food (p = 1.00).
      CONCLUSION: Food avoidance is related to child's state anxiety about an adverse
      food reaction. Food avoidance seems to be independent of a doctor's diagnosis of
      food allergy and advice on food avoidance.

PMID- 24112427
TI  - Component-resolved diagnostics for the evaluation of peanut allergy in a low
      prevalence area.
AB  - BACKGROUND: Major allergenic components of peanut from distinct geographical
      regions are widely dispersed. Most of the diagnostic studies are from countries
      with a high prevalence. There have been only few reports of allergen component
      sensitizations from countries with a low prevalence of peanut allergy. We aimed
      to investigate roles of component-resolved diagnostic (CRD) to differentiate
      peanut allergy and peanut tolerance in the Asian population from a country with
      low prevalence of peanut allergy. METHODS: Participants with peanut sensitization
      were enrolled. Clinical reactions were determined. Skin prick test (SPT) and
      specific IgE (sIgE) to peanut and related allergen components were performed.
      RESULTS: Forty subjects with peanut sensitization were included. The mean wheal
      sizes of SPT and peanut sIgE were not good predictors for differentiating peanut
      reactions. SIgE to rAra h 2 was more often found in patients with peanut allergy
      and anaphylaxis. sIgE to rAra h 9 was also more frequent in the peanut-allergic
      group but not related to severe reactions. In the peanut-tolerant group, despite
      positive SPT and/or sIgE to peanut, 90% had negative sIgE to rAha h 2 and rAra h
      9. Combining rAra h 2 and rAra h 9 resulted in high performance of the test with
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 84%, 90%, 0.89, and 0.86, respectively. The ratio between rAra h 2 sIgE
      to peanut sIgE of 0.6 can be helpful in predicting patients who will develop
      severe reaction. SIgE to cross-reactive carbohydrate determinants (CCD) was
      exclusively found in the peanut-tolerant group (33.3% vs. 0%, p = 0.012).
      CONCLUSIONS: Our study identifies three allergen components: rAra h 2, rAra h 9,
      and CCD as important components in the diagnosis of peanut allergy in an Asian
      country with low prevalence. The ratio between rArah h 2 sIgE to peanut sIgE can
      be used for predicting patients who will develop anaphylaxis.

PMID- 24112428
TI  - Natural killer cell activity and frequency of killer cell immunoglobulin-like
      receptors in children with different forms of juvenile idiopathic arthritis.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) has three major onset types with
      widely varying clinical features: systemic, polyarticular and pauciarticular. We
      assessed natural killer (NK) cell function and killer cell immunoglobulin-like
      receptor (KIR) genotypes in patients with different JIA subtypes. METHODS:
      Peripheral blood samples from 72 children with active JIA (systemic, 25;
      polyarticular, 24; pauciarticular, 23) and 25 controls were used for flow
      cytometric assessments of NK cell count, cytotoxicity, perforin, granzyme B,
      interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Samples from 220
      children with JIA (systemic, 84; polyarticular, 72; pauciarticular, 64) and 150
      controls were used for KIR2DS2, KIR2DS4, KIR3DS1, KIR2DL1, KIR2DL2, KIR2DL3 and
      KIR3DL1 typing by polymerase chain reaction with sequence-specific
      oligonucleotide probes. RESULTS: Compared with the controls, the patients with
      systemic JIA showed lower NK cell counts, cytotoxicity and perforin and granzyme
      B expression (p < 0.05), while the patients with pauci- and polyarticular JIA
      showed higher perforin and granzyme B expression (p < 0.05). NK cells produced
      higher level of TNF-alpha while lower level of IFN-gamma in the pauci- and
      polyarticular JIA groups than in the systemic JIA group (p < 0.05). No
      significant differences in KIR gene frequencies were found between the JIA
      subgroups and healthy controls, except for the positive frequency and locus
      frequency of KIR2DS4, which were lower in the systemic JIA group. CONCLUSIONS:
      Compared with poly- and pauciarticular JIA, systemic JIA is associated with
      decreased NK cell function, more IFN-gamma and less TNF-alpha secretion of NK
      cell and lower KIR2DS4 frequency.

PMID- 24112430
TI  - Pediatric allergy and immunology in Japan.
AB  - The Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) was
      started in 1966 and currently has 3613 members as of August 1, 2012. The number
      of pediatricians specializing in allergies who have been certified by the
      Japanese Society of Allergology is 817. Among these, there are 125 training
      directors and training facilities for allergy and clinical immunology. The JSPACI
      first published an asthma guideline specific for children in 2000, and this has
      been revised every 3 yrs, contributing to better control of pediatric asthma.
      Food allergy management guidelines were first developed in 2005, which have
      helped to improve the care of food allergy patients. Among 514 pediatric training
      programs by the Japanese Society of Pediatrics, there are 312 facilities
      routinely performing oral food challenges. Among these, there were already 53
      facilities performing oral immunotherapy at the end of 2011, treating 1400 cases
      of food allergy. The prevalence of pediatric allergic diseases has increased in
      Japan over the past 50 yrs. A number of International Study of Asthma and
      Allergies in Childhood surveys have been conducted in the past at specific times.
      The prevalence of wheezing among children aged 13-14 yrs in 2002 was 13.0%. Multi
      year surveys found a 1.5- to 2-fold increase every 10 yrs until 2002. However,
      according to the latest data in 2012, asthma prevalence seems to have slightly
      decreased in Japan. Food allergy mainly associated with infantile atopic eczema
      among infants younger than 1 yr of age is the most common form as with other
      developed countries. The estimated food allergy prevalence based on data from
      several surveys is 5-10% among infants (0-6 yrs) and 1-2% among schoolchildren (6
      15 yrs). A variety of patients suffering from primary deficiency syndrome have
      been actively analyzed. Previously, antibody defects and well-defined syndromes
      with immunodeficiency were analyzed, but recent research is focusing on not only
      acquired immune disorders but also on innate immune disorders. In contrast to the
      widespread use of oral immunotherapy, one immediate issue is to develop and
      reassess subcutaneous and sublingual immunotherapies for mite and Japanese cedar
      pollen antigens that have been disused in Japan since the 1990s. 

PMID- 24112429
TI  - Exposures to molds in school classrooms of children with asthma.
AB  - BACKGROUND: Students spend a large portion of their day in classrooms which may
      be a source of mold exposure. We examined the diversity and concentrations of
      molds in inner-city schools and described differences between classrooms within
      the same school. METHODS: Classroom airborne mold spores, collected over a 2 day
      period, were measured twice during the school year by direct microscopy. RESULTS:
      There were 180 classroom air samples collected from 12 schools. Mold was present
      in 100% of classrooms. Classrooms within the same school had differing mold
      levels and mold diversity scores. The total mold per classroom was 176.6 +/- 4.2
      spores/m3 (geometric mean +/- standard deviation) and ranged from 11.2 to
      16,288.5 spores/m3. Mold diversity scores for classroom samples ranged from 1 to
      19 (7.7 +/- 3.5). The classroom accounted for the majority of variance (62%) in
      the total mold count, and for the majority of variance (56%) in the mold
      diversity score versus the school. The species with the highest concentrations
      and found most commonly included Cladosporium (29.3 +/- 4.2 spores/m3),
      Penicillium/Aspergillus (15.0 +/- 5.4 spores/m3), smut spores (12.6 +/- 4.0
      spores/m3), and basidiospores (6.6 +/- 7.1 spores/m3). CONCLUSIONS: Our study
      found that the school is a source of mold exposure, but particularly the
      classroom microenvironment varies in quantity of spores and species among
      classrooms within the same school. We also verified that visible mold may be a
      predictor for higher mold spore counts. Further studies are needed to determine
      the clinical significance of mold exposure relative to asthma morbidity in
      sensitized and non-sensitized asthmatic children.

PMID- 24112431
TI  - Clinical significance of increased peripheral blood CD4(+) CD28(-) T cells of
      asthmatic children.

PMID- 24112432
TI  - Coral feeding on microalgae assessed with molecular trophic markers.
AB  - Herbivory in corals, especially for symbiotic species, remains controversial. To
      investigate the capacity of scleractinian and soft corals to capture microalgae,
      we conducted controlled laboratory experiments offering five algal species: the
      cryptophyte Rhodomonas marina, the haptophytes Isochrysis galbana and Phaeocystis
      globosa, and the diatoms Conticribra weissflogii and Thalassiosira pseudonana.
      Coral species included the symbiotic soft corals Heteroxenia fuscescens and
      Sinularia flexibilis, the asymbiotic scleractinian coral Tubastrea coccinea, and
      the symbiotic scleractinian corals Stylophora pistillata, Pavona cactus and
      Oculina arbuscula. Herbivory was assessed by end-point PCR amplification of algae
      specific 18S rRNA gene fragments purified from coral tissue genomic DNA extracts.
      The ability to capture microalgae varied with coral and algal species and could
      not be explained by prey size or taxonomy. Herbivory was not detected in S.
      flexibilis and S. pistillata. P. globosa was the only algal prey that was never
      captured by any coral. Although predation defence mechanisms have been shown for
      Phaeocystis spp. against many potential predators, this study is the first to
      suggest this for corals. This study provides new insights into herbivory in
      symbiotic corals and suggests that corals may be selective herbivorous feeders.

PMID- 24112433
TI  - Examining roles pharmacists assume in disasters: a content analytic approach.
AB  - OBJECTIVE: Numerous practice reports recommend roles pharmacists may adopt during
      disasters. This study examines the peer-reviewed literature for factors that
      explain the roles pharmacists assume in disasters and the differences in roles
      and disasters when stratified by time. METHODS: Quantitative content analysis was
      used to gather data consisting of words and phrases from peer-reviewed pharmacy
      literature regarding pharmacists' roles in disasters. Negative binomial
      regression and Kruskal-Wallis nonparametric models were applied to the data.
      RESULTS: Pharmacists' roles in disasters have not changed significantly since the
      1960s. Pharmaceutical supply remains their preferred role, while patient
      management and response integration roles decrease in context of common,
      geographically widespread disasters. Policy coordination roles, however,
      significantly increase in nuclear terrorism planning. CONCLUSIONS: Pharmacists'
      adoption of nonpharmaceutical supply roles may represent a problem of accepting a
      paradigm shift in nontraditional roles. Possible shortages of personnel in future
      disasters may change the pharmacists' approach to disaster management.

PMID- 24112434
TI  - Evaluation of a catalase-based urine test for the detection of urinary tract
      infection in dogs and cats.
AB  - BACKGROUND: Bacterial infection of the urinary tract is a common disorder in dogs
      and cats. Although microscopic examination of urine sediment is routinely used to
      screen for infection, this test can lack sensitivity or require expertise. A
      reliable in-clinic screening test would be a useful adjunct for the
      identification of dogs and cats with bacterial urinary tract infection (UTI).
      HYPOTHESIS: That a catalase-based urine test (Accutest UriscreenTM) is a more
      sensitive screening test for UTI in dogs and cats than urine microscopic sediment
      examination. ANIMALS: One hundred and sixty client-owned dogs and cats. METHODS:
      Surplus urine from animals presented to a veterinary teaching hospital was used
      in this prospective observational study. A routine urinalysis, aerobic bacterial
      culture, and the Uriscreen test were performed on cystocentesis samples.
      Sensitivity and specificity with 95% confidence intervals and positive and
      negative likelihood ratios were calculated for Uriscreen and microscopic sediment
      examination using culture results as the gold standard. RESULTS: Bacterial
      culture was positive in 27/165 (16.4%) samples. The sensitivity, specificity, and
      positive and negative likelihood ratios for the Uriscreen were 89%, 71%, 3.0, and
      0.15, respectively. Sensitivity, specificity, and positive and negative
      likelihood ratios for urine sediment microscopic examination were 78%, 90%, 7.8,
      and 0.24, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The Uriscreen is a
      more sensitive screening test for UTI in dogs and cats than sediment examination;
      however, the urine sediment examination was more specific. A negative Uriscreen
      result helps exclude UTI; however, urine bacterial culture is still necessary to
      exclude or confirm UTI in all cases.

PMID- 24112435
TI  - cudaMap: a GPU accelerated program for gene expression connectivity mapping.
AB  - BACKGROUND: Modern cancer research often involves large datasets and the use of
      sophisticated statistical techniques. Together these add a heavy computational
      load to the analysis, which is often coupled with issues surrounding data
      accessibility. Connectivity mapping is an advanced bioinformatic and
      computational technique dedicated to therapeutics discovery and drug re-purposing
      around differential gene expression analysis. On a normal desktop PC, it is
      common for the connectivity mapping task with a single gene signature to take >
      2h to complete using sscMap, a popular Java application that runs on standard
      CPUs (Central Processing Units). Here, we describe new software, cudaMap, which
      has been implemented using CUDA C/C++ to harness the computational power of
      NVIDIA GPUs (Graphics Processing Units) to greatly reduce processing times for
      connectivity mapping. RESULTS: cudaMap can identify candidate therapeutics from
      the same signature in just over thirty seconds when using an NVIDIA Tesla C2050
      GPU. Results from the analysis of multiple gene signatures, which would
      previously have taken several days, can now be obtained in as little as 10
      minutes, greatly facilitating candidate therapeutics discovery with high
      throughput. We are able to demonstrate dramatic speed differentials between GPU
      assisted performance and CPU executions as the computational load increases for
      high accuracy evaluation of statistical significance. CONCLUSION: Emerging
      'omics' technologies are constantly increasing the volume of data and information
      to be processed in all areas of biomedical research. Embracing the multicore
      functionality of GPUs represents a major avenue of local accelerated computing.
      cudaMap will make a strong contribution in the discovery of candidate
      therapeutics by enabling speedy execution of heavy duty connectivity mapping
      tasks, which are increasingly required in modern cancer research. cudaMap is open
      source and can be freely downloaded from http://purl.oclc.org/NET/cudaMap.

PMID- 24112436
TI  - Diabetes and thrombolysis for acute stroke: a clear benefit for diabetics.
AB  - BACKGROUND AND PURPOSE: Diabetes is a predictor for poor outcome after
      thrombolysis in stroke patients, and early post-stroke glycaemia is associated
      with higher rates of post-thrombolytic symptomatic intracerebral haemorrhages
      (SICHs). Diabetic stroke patients may nevertheless profit from thrombolysis.
      Here, we compared outcome data of matched thrombolysed and non-thrombolysed
      diabetic and non-diabetic stroke patients from a national database. METHODS: The
      outcomes of 1079 matched quadruples, each consisting of a thrombolysed diabetic,
      a non-thrombolysed diabetic, a thrombolysed non-diabetic and a non-thrombolysed
      non-diabetic case (a total of 4316 cases), enrolled in the Austrian Stroke Unit
      Registry (2004-2013), were compared. Patients were matched according to sex, age,
      stroke severity, pre-stroke disability and prior stroke. RESULTS: A regression
      model with improvement as depending variable found no effect of diabetes (P =
      0.158) or the interaction diabetes * thrombolysis (P = 0.507), whereas the effect
      of thrombolysis itself was highly significant (P < 0.001). Functional outcome
      (modified Rankin Scale) was significantly better in thrombolysed than in non
      thrombolysed diabetic patients at discharge from the stroke-unit (P < 0.001) and
      3 months later (P = 0.006). No significant differences were found in the number
      of SICHs after thrombolytic treatment between diabetic (4.9%) and non-diabetic
      strokes (3.5%). Both groups had a higher risk of SICH compared with the non
      thrombolysed groups (diabetics 2.6%, non-diabetics 2.5%). Due to lack of
      documentation, the effect of admission blood glucose on SICH was not
      investigated. CONCLUSIONS: Data from this nationwide survey show that diabetic
      stroke patients receive a substantial benefit from thrombolysis, and therefore
      diabetic strokes should not be excluded from thrombolytic treatment.

PMID- 24112437
TI  - The therapeutic potential of bone marrow-derived mesenchymal stromal cells on
      hepatocellular carcinoma.
AB  - Mesenchymal stromal cells (MSCs) are more often obtained from adult and
      extraembryonic tissues, with the latter sources being likely better from a
      therapeutic perspective. MSCs show tropism towards inflamed or tumourigenic
      sites. Mechanisms involved in MSC recruitment into tumours are comprehensively
      analysed, including chemoattractant signalling axes, endothelial adhesion and
      transmigration. In addition, signals derived from hepatocellular carcinoma (HCC)
      tumour microenvironment and their influence in MSC tropism and tumour recruitment
      are dissected, as well as the present controversy regarding their influence on
      tumour growth and/or metastasis. Finally, evidences available on the use of MSCs
      and other selected progenitor/stem cells as vehicles of antitumourigenic genes
      are discussed. A better knowledge of the mechanisms involved in progenitor/stem
      cell recruitment to HCC tumours is proposed in order to enhance their tumour
      targeting which may result in improvements in cell-based gene therapy strategies.

PMID- 24112438
TI  - Minor splicing pathway is not minor any more: implications for the pathogenesis
      of motor neuron diseases.
AB  - To explore the molecular pathogenesis of amyotrophic lateral sclerosis (ALS), the
      nuclear function of TAR-DNA binding protein 43 kDa (TDP-43) must be elucidated.
      TDP-43 is a nuclear protein that colocalizes with Cajal body or Gem in cultured
      cells. Several recent studies have reported that the decreasing number of Gems
      accompanied the depletion of the causative genes for ALS, TDP-43 and FUS. Gems
      play an important role in the pathogenesis of spinal muscular atrophy. Gems are
      the sites of the maturation of spliceosomes, which are composed of uridylate-rich
      (U) snRNAs (small nuclear RNAs) and protein complex, small nuclear
      ribonuclearprotein (snRNP). Spliceosomes regulate the splicing of pre-mRNA and
      are classified into the major or minor classes, according to the consensus
      sequence of acceptor and donor sites of pre-mRNA splicing. Although the major
      class of spliceosomes regulates most pre-mRNA splicing, minor spliceosomes also
      play an important role in regulating the splicing or global speed of pre-mRNA
      processing. A mouse model of spinal muscular atrophy, in which the number of Gems
      is decreased, shows fewer subsets U snRNAs. Interestingly, in the central nervous
      system, U snRNAs belonging to the minor spliceosomes are markedly reduced. In
      ALS, the U12 snRNA is decreased only in the tissue affected by ALS and not in
      other tissues. Although the molecular mechanisms underlying the decreased U12
      snRNA resulting in cell dysfunction and cell death in motor neuron diseases
      remain unclear, these findings suggest that the disturbance of nuclear bodies and
      minor splicing may underlie the common molecular pathogenesis of motor neuron
      diseases.

PMID- 24112439
TI  - Infants' goal anticipation during failed and successful reaching actions.
AB  - The ability to interpret and predict the actions of others is crucial to social
      interaction and to social, cognitive, and linguistic development. The current
      study provided a strong test of this predictive ability by assessing (1) whether
      infants are capable of prospectively processing actions that fail to achieve
      their intended outcome, and (2) how infants respond to events in which their
      initial predictions are not confirmed. Using eye tracking, 8-month-olds, 10-month
      olds, and adults watched an actor repeatedly reach over a barrier to either
      successfully or unsuccessfully retrieve a ball. Ten-month-olds and adults
      produced anticipatory looks to the ball, even when the action was unsuccessful
      and the actor never achieved his goal. Moreover, they revised their initial
      predictions in response to accumulating evidence of the actor's failure. Eight
      month-olds showed anticipatory looking only after seeing the actor successfully
      grasp and retrieve the ball. Results support a flexible, prospective social
      information processing ability that emerges during the first year of life. 

PMID- 24112440
TI  - Improving utilization of and retention in PMTCT services: can behavioral
      economics help?
AB  - BACKGROUND: The most recent strategic call to action of the World Health
      Organization sets the elimination of pediatric HIV as a goal. While recent
      efforts have focused on building infrastructure and ensuring access to high
      quality treatment, we must now turn our focus to the behavior change needed to
      eliminate vertical transmission. We make the case for the application of concepts
      from the field of behavioral economics to prevention of mother-to-child
      transmission (PMTCT) programs to more effectively address demand-side issues of
      uptake and retention. DISCUSSION: We introduce five concepts from the field of
      behavioral economics and discuss their application to PMTCT programs: 1) Mentor
      mothers who come from similar circumstances as PMTCT patients can serve as social
      references who provide temporally salient modeling of utilization of services and
      adherence to treatment. 2) Economic incentives, like cell phone minutes or food
      vouchers, that reward adherence to PMTCT protocols leverage present bias, the
      observation that people are generally biased toward immediate versus future
      awards. 3) Default bias, our preference for the default option, is already being
      used in many countries in the form of opt-out testing, and could be expanded to
      all PMTCT programs. 4) We are hardwired to avoid loss more than to pursue an
      equivalent gain. PMTCT programs can take advantage of loss aversion through the
      use of commitment contracts that incentivize mothers to return to the clinic in
      order to avoid both reputational and financial loss. SUMMARY: Eliminating
      vertical transmission of HIV is an ambitious goal. To close the remaining gap,
      innovations are needed to address demand for PMTCT services. Behavioral economics
      offers a set of tools that can be engineered into PMTCT programs to increase
      uptake and improve retention with minimal investment.

PMID- 24112442
TI  - Self-reported general health and Body Mass Index: a U-shaped relationship?
AB  - OBJECTIVES: A sizable literature demonstrates an increased likelihood of self
      reported poor health with increasing Body Mass Index (BMI). A U-shaped
      relationship between BMI and health is evident in research but it is not believed
      that the health of people who are underweight gets the attention it deserves. The
      relationship between BMI categories and poor general health including those
      persons who are underweight has been investigated. STUDY DESIGN: Cross-sectional
      study. METHODS: Data were obtained from the Health Survey for England pooled for
      2006-08 to provide a sample of 26,596 adults aged 16-74 in a series of binary
      logistic regression models to determine the likelihood of people reporting their
      general health as being poor. RESULTS: A clear U-shaped relationship between BMI
      and health has been found for controlling for individual level demographic, socio
      economic and health-related behaviour variables and area deprivation.
      CONCLUSIONS: The literature largely focuses on the relationship between obesity
      and health and this is understandable given that many more persons are obese than
      are underweight. A person who is underweight is about as likely to report poor
      general health as a person who is obese.

PMID- 24112441
TI  - Self-collected versus clinician-collected sampling for sexually transmitted
      infections: a systematic review and meta-analysis protocol.
AB  - BACKGROUND: Three meta-analyses and one systematic review have been conducted on
      the question of whether self-collected specimens are as accurate as clinician
      collected specimens for STI screening. However, these reviews predate 2007 and
      did not analyze rectal or pharyngeal collection sites. Currently, there is no
      consensus on which sampling method is the most effective for the diagnosis of
      genital chlamydia (CT), gonorrhea (GC) or human papillomavirus (HPV) infection.
      Our meta-analysis aims to be comprehensive in that it will examine the evidence
      of whether self-collected vaginal, urine, pharyngeal and rectal specimens provide
      as accurate a clinical diagnosis as clinician-collected samples (reference
      standard). METHODS/DESIGN:  INCLUSION AND EXCLUSION CRITERIA: Eligible studies
      include both randomized and non-randomized controlled trials, pre- and post-test
      designs, and controlled observational studies. SEARCH STRATEGY: The databases
      that will be searched include the Cochrane Database of Systematic Reviews, Web of
      Science, Database of Abstracts of Reviews of Effects (DARE), EMBASE and
      PubMed/Medline. DATA COLLECTION AND ANALYSIS: Data will be abstracted
      independently by two reviewers using a standardized pre-tested data abstraction
      form. Heterogeneity will be assessed using the Q2 test. Sensitivity and
      specificity estimates with 95% confidence intervals as well as negative and
      positive likelihood ratios will be pooled and weighted using random effects meta
      analysis, if appropriate. A hierarchical summary receiver operating
      characteristics curve for self-collected specimens will be generated. DISCUSSION:
      This synthesis involves a meta-analysis of self-collected samples (urine,
      vaginal, pharyngeal and rectal swabs) versus clinician-collected samples for the
      diagnosis of CT, GC and HPV, the most prevalent STIs. Our systematic review will
      allow patients, clinicians and researchers to determine the diagnostic accuracy
      of specimens collected by patients compared to those collected by clinicians in
      the detection of chlamydia, gonorrhea and HPV.

PMID- 24112443
TI  - Surrogate markers of visceral adipose tissue in treated HIV-infected patients:
      accuracy of waist circumference determination.
AB  - OBJECTIVES: The accuracy of the use of anthropometrics to quantify visceral
      adipose tissue (VAT) in treated HIV-infected patients is unknown. We evaluated
      the predictive accuracy of waist circumference (WC) with and without dual-energy
      X-ray absorptiometry (DXA)-derived trunk : limb fat ratio [fat mass ratio (FMR)]
      as surrogates for VAT determined using computerized axial tomography (CT
      determined VAT). METHODS: We performed a retrospective cohort analysis of treated
      HIV-infected male patients followed at the Modena HIV Clinic. We developed
      prediction equations for VAT using linear regression analysis and Spearman
      correlations. Receiver operating characteristic (ROC) analysis evaluated the
      accuracy of WC alone or with FMR at discrete VAT thresholds. RESULTS: The 1500
      Caucasian male patients had a median age of 45 years, body mass index (BMI) of
      24, WC of 87 cm, VAT area of 127 cm(2) and body fat percentage of 14%. The
      correlation between WC-predicted VAT and CT-VAT was 0.613, and this increased
      significantly if FMR was added. The WC-associated R(2) of 0.35 increased to 0.51
      if the prediction equation included WC plus FMR. The area under the ROC curve
      (AUC) using WC was 0.795-0.820 at all VAT thresholds. The positive predictive
      value (PPV) and negative predictive value (NPV) changed reciprocally at CT-VAT
      thresholds from 75 to 200 cm(2) and ranged from 0.72 to 0.74, respectively, at a
      representative VAT of 125 cm(2). Adding the FMR to the predictive equations
      increased the AUC in the range of 0.854-0.889 with the PPV and NPV increasing
      minimally, ranging from 0.780 to 0.821. Limits of precision were wide, especially
      at the highest CT-VAT levels, and varied from 24 to 68 cm(2). CONCLUSIONS: WC is
      a limited surrogate for CT-VAT in this population and DXA-derived parameters do
      not improve performance indices to a clinically relevant level. These findings
      should inform the applicability of WC to predict VAT in treated HIV-infected male
      patients.

PMID- 24112444
TI  - Does continuous endurance exercise in water elicit a higher release of ANP and
      BNP and a higher plasma concentration of FFAs in pre-obese and obese men than
      high intensity intermittent endurance exercise? - study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Atrial natriuretic peptides (ANP) and Brain natriuretic peptides
      (BNP) stimulate fat cell plasma membrane receptors. They are potent lipolytic
      agents on isolated fat cells from subcutaneous adipose tissue. The physiological
      effects of continuous endurance exercise on ANP release and plasma free fatty
      acids (FFA) concentrations have been well described. The enhancement of fat
      metabolism using high intensity intermittent exercise protocols has been assessed
      in more recent investigations. The combined effects of endurance exercise and
      water immersion on ANP and FFA plasma concentration and the magnitude of excess
      post-exercise oxygen consumption (EPOC) might be further enhanced by choosing the
      most effective exercise protocol. Exercise modalities may play a significant role
      in the future prevention and treatment of obesity. METHODS/DESIGN: The two
      testing trials will be performed according to a randomized and cross-over design.
      Twenty healthy sedentary pre-obese and obese class-1 men will be scrutinized with
      regard to their metabolic responses to continuous exercise in water and to high
      intensity endurance exercise in water. Both trials will be matched for energy
      expenditure. After preliminary testing, the tests will be conducted as repeated
      measurements. The two different exercise protocols will be compared. The aims of
      the study are to investigate (1) whether continuous endurance exercise or high
      intensity intermittent endurance exercise in water elicits both a higher release
      of ANP and BNP and a higher plasma concentration of glycerol and (2) to determine
      whether continuous endurance exercise in water or a high intensity intermittent
      endurance exercise in water would lead to a more pronounced short term (two
      hours) EPOC effect. DISCUSSION: If our hypothesis would be confirmed, the most
      effective exercise protocol based on the combined effects of high intensity
      endurance exercise and water immersion on ANP and BNP release and glycerol plasma
      concentrations can be identified. Moreover, the magnitude of the EPOC effect can
      be augmented. Our study would provide a major contribution for creating optimized
      exercise modalities in the prevention and treatment of obesity. TRIAL
      REGISTRATION: Current controlled trials, ISRCTN95488515.

PMID- 24112445
TI  - Role of Community Based Savings Groups (CBSGs) enhancing the utilization of
      community midwives in Chitral district of Pakistan.
AB  - BACKGROUND: Maternal and infant mortality rates in the district of Chitral in
      Pakistan are alarmingly high. One of the major reasons for this is the inability
      of women to access skilled care due to the high costs associated with traveling
      and utilizing such services. The Aga Khan Health Services, Pakistan (AKHSP) in
      partnership with the national and provincial Maternal, Neonatal and Child Health
      (MNCH) program, deployed 28 community midwives (CMWs) in remote villages of
      Chitral district. This program has also established Community-Based Savings
      Groups (CBSGs) to support and facilitate access to MNCH services, in particular
      those delivered by the CMWs. CBSGs are a simple yet cost-effective and
      sustainable means of providing basic financial services to low income,
      marginalized, rural populations.The link between CBSGs and utilization of MNCH
      services is not well understood. This study will assess the relationship between
      women membership of CBSGs and their utilization of MNCH services, specifically
      those offered by CMWs, in the community. METHODS: The research question will be
      answered through guided interviews of women in the target population who have
      delivered within one month. The outcome variable will be the utilization of full
      continuum of skilled MNCH care (disaggregated by 1+ ANC, 1+ PNC and skilled
      delivery). The primary independent variable of interest will be participation in
      a CBSG.Focus Group Discussions (FGDs) will be conducted to generate further
      understanding and information about the social and financial factors that
      contribute to health behavior and health provider decision-making during
      pregnancy.Analysis will be tailored to answer how CBSGs, directly or indirectly,
      facilitate greater financial and/or social access to CMW services for pregnant
      women. Furthermore, the extent to which financial or social empowerment through a
      CBSG leads to greater utilization of CMW services. DISCUSSION: The role of CBSGs
      and their interlink with the CMWs services to be replicated in other comparable
      areas in Pakistan as a viable mean to increase MNCH service utilization amongst
      rural, low income, and marginalized communities. Findings from this research will
      be disseminated through community, national, and international channels
      consisting of policy makers and social society groups.

PMID- 24112446
TI  - Tangential shave removal of basal cell carcinoma.

PMID- 24112448
TI  - Control of cestode zoonoses in Asia: role of basic and applied science. Preface.

PMID- 24112447
TI  - Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in
      rats with adjuvant-induced arthritis.
AB  - The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid
      arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the
      mechanism by which this occurs still remains obscure. In the present study, we
      investigated the role of AT2R in the treatment of rats with adjuvant-induced
      arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with
      losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day
      14 to day 28. Arthritis was evaluated by the arthritis index and histological
      examination. Angiotensin II, tumour necrosis factor-alpha, and VEGF levels were
      examined by ELISA. The expression of AT1R and AT2R was detected by western blot
      and immunohistochemistry analysis. After stimulation with interleukin-1beta in
      vitro, the effects of the AT2R agonist CGP42112 (10(-8) -10(-5)  M) on the
      chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by
      using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10
      and 20 MUg/kg) were evaluated in vivo by intra-articular injection in AIA rats.
      After treatment with losartan, the down-regulation of AT1R expression and up
      regulation of AT2R expression in the spleen and synovium of AIA rats correlated
      positively with reduction in the polyarthritis index. Treatment with CGP42112
      inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up
      regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20
      MUg/kg) ameliorated the arthritis index and histological signs of arthritis. In
      summary, the present study strongly suggests that the up-regulation of AT2R might
      be an additional mechanism by which losartan exerts its therapeutic effects in
      AIA rats. 

PMID- 24112449
TI  - Genotypic relationships between Taenia saginata, Taenia asiatica and their
      hybrids.
AB  - Partial sequences of the DNA polymerase delta (pold) gene from Taenia saginata
      like adult worms were sequenced. Phylogenetic analysis revealed that pold gene
      sequences were clearly divided into two clades, differing from each other in five
      to seven nucleotides. There is little doubt that T. saginata and Taenia asiatica
      were once separated into two distinct taxa as has been concluded in previous
      studies. On the other hand, most of the adult worms, which were identified as T.
      asiatica using mitochondrial DNA, were homozygous for an allele that originated
      from the allele of T. saginata via single nucleotide substitution. These results
      indicate that most of the adult worms, which had been called T. asiatica, are not
      actually 'pure T. asiatica' but instead originated from the hybridization of
      'pure T. saginata' and 'pure T. asiatica'.

PMID- 24112450
TI  - Vardenafil improves penile erection in type 2 diabetes mellitus patients with
      erectile dysfunction: role of tropomyosin.
AB  - INTRODUCTION: Evidences have been suggested that phosphodiesterase type 5 (PDE5)
      inhibition promotes vasculoprotective benefits in patients with cardiovascular
      diseases. AIM: The aim of this study is to analyze the systemic effect of PDE5
      inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED)
      determining changes in the expression levels of plasma proteins. METHODS:
      Seventeen patients with controlled type 2 diabetes mellitus and ED were included
      in the study. Patients received vardenafil hydrochloride 20 mg on demand during
      12 weeks. At the beginning and 12 weeks after vardenafil administration, plasma
      samples were collected and analyzed using proteomics. MAIN OUTCOME MEASURES:
      International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and
      plasma protein expression before and after vardenafil administration.
      Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and
      cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic
      endothelial cells (BAECs). RESULTS: The IIEF-EFD score was markedly improved
      after 12 weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin
      isotypes 4 and 6 and beta-tropomyosin were decreased, whereas apolipoprotein AI
      isoype 5 was increased 12 weeks after vardenafil administration. Only beta
      tropomyosin plasma levels were inversely correlated with IIEF-EFD score.
      Tropomyosin has been added to cultured BAECs and after 24 hours reduced the
      protein expression level of sGC-beta1 subunit and decreased the cGMP content.
      Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as
      compared with control BAECs. Vardenafil (10 MUg/mL) did not modify sGC-beta1
      subunit expression in tropomyosin + vardenafil-incubated BAECs; however,
      vardenafil significantly reversed the reduction of cGMP content induced by
      tropomyosin. CONCLUSION: Vardenafil administration improved erectile
      functionality in controlled type 2 diabetes mellitus patients with ED, which was
      associated with reduction of circulating plasma beta-tropomyosin levels.
      Tropomyosin affected by itself the cGMP generating system suggesting a possible
      new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP
      content elicited by tropomyosin in BAECs.

PMID- 24112451
TI  - Methylene tetrahydrofolate reductase polymorphisms and homocysteine level in
      heart defects.
AB  - BACKGROUND: While several single nucleotide polymorphisms are known to influence
      the metabolism of folate, the methylene tetrahydrofolate reductase (MTHFR) gene
      has been the most extensively studied. The aim of this study was to investigate
      the relationship between the MTHFR polymorphisms 1298A>C and 677C>T and
      congenital heart disease. In addition, the relationship between these gene
      polymorphisms and homocysteine level was determined in Turkish subjects. METHODS:
      Patients with non-syndromic congenital heart defects who were admitted to the
      Pediatric Cardiology Unit at Hacettepe University Ihsan Dogramaci Children's
      Hospital, Ankara, Turkey between June 2002 and June 2003 were recruited for the
      study. A total of 163 children with congenital heart defects (mean age, 7.63 +/-
      6.03 years; M/F, 93/70) and 93 healthy controls were analyzed. RESULTS: When
      evaluated either separately or together, there were no differences in the
      frequency of MTHFR 677C>T or 1298A>C polymorphisms between the children with
      congenital heart defects and the control group. The results were the same when
      considering only conotruncal defects. Those with the 677C>T polymorphism had
      significantly lower homocysteine level (P = 0.004), but the 1298A>C polymorphism
      was not related to homocysteine level. CONCLUSION: No relationship was found
      between congenital heart defects and 1298A>C or 677C>T polymorphisms. The 677C>T
      polymorphism was related to low homocysteine level. Because there is often much
      heterogeneity between populations, this study should be conducted in different
      populations and with larger numbers of participants.

PMID- 24112452
TI  - Experimental hybridization and backcrossing reveal forces of reproductive
      isolation in Microbotryum.
AB  - BACKGROUND: Hybridization and reproductive isolation are central to the origin
      and maintenance of species, and especially for sympatric species, gene flow is
      often inhibited through barriers that depend upon mating compatibility factors.
      The anther-smut fungi (genus Microbotryum) serve as models for speciation in the
      face of sympatry, and previous studies have tested for but not detected
      assortative mating. In addition, post-mating barriers are indicated by reduced
      fitness of hybrids, but sources of those barriers (i.e. ecological maladaptation
      or genetic incompatibilities) have not yet been detected. Here, backcrossing
      experiments, specifically controlling for the fungal species origins of the
      mating compatibility factors, were used to investigate reproductive isolation in
      the recently-derived species Microbotryum lychnidis-dioicae and Microbotryum
      silenes-dioicae. RESULTS: Assortative mating was detected during backcrossing and
      was manifested by the preferential conjugation of the hybrid-produced gametes
      with non-hybrid gametes containing mating compatibility factors from the same
      parental species. Patterns of post-mating performance supported either a level of
      extrinsic isolation mechanism, where backcross progeny with a higher proportion
      of the pathogen genome adapted to the particular host environment were favored,
      or an infection advantage attributed to greater genetic contribution to the
      hybrid from the M. lychnidis-dioicae genome. CONCLUSION: The use of controlled
      backcrossing experiments reveals significant species-specific mating type effects
      on conjugations between recently-derived sister species, which are likely to play
      important roles in both maintaining species separation and the nature of hybrids
      lineages that emerge in sympatry between Microbotryum species.

PMID- 24112453
TI  - Advantages and limitations of the new anticoagulants.
AB  - During recent years, three new anticoagulants (dabigatran, rivaroxaban and
      apixaban) have been introduced to the market, probably with one more
      anticoagulant (edoxaban) in the next 2 years. This review is not intended to
      compare the efficacy and risks of these new agents, but rather to detail the
      advantages and limitations. The pharmacokinetic characteristics of these drugs
      have few drug and food interactions, predictable dose responses, and rapid onset
      and offset, thus resulting in simplified management of the patient requiring
      anticoagulant therapy. No routine laboratory monitoring is required. A somewhat
      unexpected, but exciting observation involving the new anticoagulants, is the
      uniform reduction in intracranial bleeding by one-half compared with warfarin.
      The potential limitations of the new anticoagulants include uncertainty regarding
      assessment of drug levels, safe drug levels for major surgery, management of
      major bleeding, renal dependence, multiple dose regimens, adherence in the
      absence of frequent monitoring and unknown, rare side effects that were not
      captured in the trials. This review should clarify some of these concerns. 

PMID- 24112454
TI  - Prevalence and risk factors for cardiac diseases in a hospital-based population
      of 3,434 horses (1994-2011).
AB  - BACKGROUND: Risk factors for cardiac diseases in horses have not been explored in
      a large population of animals. OBJECTIVES: To describe risk factors for various
      cardiac diseases in a hospital-based population of horses. ANIMALS: Files of
      3,434 horses admitted at the Internal Medicine Department of the Liege Equine
      Teaching Hospital between 1994 and 2011 were reviewed and of those, 284 were
      categorized as having moderate-to-severe cardiac disease. METHODS: Observational
      study. After calculating prevalence for each cardiac disease, we tested whether
      breed (chi-square test) or sex, age, body weight (BW), and other cardiac diseases
      (logistic regressions) were risk factors (p < .05 significant). RESULTS: Mitral
      regurgitation (MR, 4.4%), atrial fibrillation (AF, 2.3%), aortic regurgitation
      (AR, 2.1%), and tricuspid regurgitation (TR, 1.7%) were the most common cardiac
      abnormalities detected. Determinants were male sex and increasing age for AR (OR
      = 2.03, CI = 1.07-4.94), racehorses breed and middle-age for TR (OR = 4.36; CI =
      1.10-17.24), and high BW for AF (OR = 3.54; CI = 1.67-7.49). MR was the most
      common valvular disease associated with AF, clinically important ventricular
      arrhythmia, pulmonary regurgitation (PR), and congestive heart failure (CHF). TR
      was also associated with AF, PR, and CHF; AR was not associated with CHF.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Several previously suspected risk factors
      for a variety of equine cardiac diseases are statistically confirmed and other
      risk factors are highlighted in the studied hospital-based population. These
      observations should be taken into account in health and sport's monitoring of
      horses presenting predisposing factors.

PMID- 24112455
TI  - A model to predict antiviral treatment in HBeAg negative chronic hepatitis B with
      alanine aminotransferase<=2 upper limit of normal.
AB  - BACKGROUND & AIMS: Liver histological assessment is essential for predicting
      antiviral therapy in HBeAg negative chronic hepatitis B (CHB) patients with serum
      alanine aminotransferase (ALT)<=2 upper limit of normal (ULN). The aim was to
      establish a model to predict antiviral treatment for those patients without liver
      biopsy. METHODS: Three hundred and one consecutive treatment naive HBeAg negative
      CHB patients with HBV DNA>=2000 IU/ml and ALT<=2 ULN were retrospectively
      enrolled, among which 158 patients were for the training set and 143 for
      validation set. A multivariate logistic regression model was constructed in the
      training set and validated in the validation set. RESULTS: Our model identified
      four independent factors for the timing of treatment: Age (OR 1.050, 95%CI 1.004
      1.098), Ln(aspartate aminotransferase) (OR 17.425, 95%CI 5.394-56.292), Log10
      [HBV DNA] (OR 0.704, 95%CI 0.514-0.963) and platelet (OR 0.980, 95%CI 0.970
      0.990). It showed 94% sensitivity, 88% negative predictive value (NPV) in the
      training set and 93% sensitivity, 85% NPV in the validation set using the low cut
      off point of 5.16. Meanwhile, it showed 92% specificity, 88% positive predictive
      value (PPV) in the training set and 94% specificity, 92% PPV in the validation
      set using the high cut-off point of 7.26. It could predict treatment for 179 of
      301(59%) patients without biopsy. CONCLUSIONS: We established a model to predict
      antiviral therapy in HBeAg negative CHB patients with ALT<=2 ULN. Antiviral
      treatment should be initiated if the model value>7.26 and not if its value<=5.16.
      Liver biopsy is needed only when its value between the two points.

PMID- 24112456
TI  - American Diabetes Association 73rd Scientific Sessions, Chicago, Illinois, USA,
      2013.

PMID- 24112457
TI  - Extranasopharyngeal angiofibroma of the left lower turbinate: A case report.

PMID- 24112458
TI  - Experimental evidence that evolutionary relatedness does not affect the
      ecological mechanisms of coexistence in freshwater green algae.
AB  - The coexistence of competing species depends on the balance between their fitness
      differences, which determine their competitive inequalities, and their niche
      differences, which stabilise their competitive interactions. Darwin proposed that
      evolution causes species' niches to diverge, but the influence of evolution on
      relative fitness differences, and the importance of both niche and fitness
      differences in determining coexistence have not yet been studied together. We
      tested whether the phylogenetic distances between species of green freshwater
      algae determined their abilities to coexist in a microcosm experiment. We found
      that niche differences were more important in explaining coexistence than
      relative fitness differences, and that phylogenetic distance had no effect on
      either coexistence or on the sizes of niche and fitness differences. These
      results were corroborated by an analysis of the frequency of the co-occurrence of
      325 pairwise combinations of algal taxa in > 1100 lakes across North America.
      Phylogenetic distance may not explain the coexistence of freshwater green algae.

PMID- 24112459
TI  - Contrasting primary successional trajectories of fungi and bacteria in retreating
      glacier soils.
AB  - Early community assembly of soil microbial communities is essential for
      pedogenesis and development of organic legacies. We examined fungal and bacterial
      successions along a well-established temperate glacier forefront chronosequence
      representing ~70 years of deglaciation to determine community assembly. As
      microbial communities may be heavily structured by establishing vegetation, we
      included nonvegetated soils as well as soils from underneath four plant species
      with differing mycorrhizal ecologies (Abies lasiocarpa, ectomycorrhizal; Luetkea
      pectinata, arbuscular mycorrhizal; Phyllodoce empetriformis, ericoid mycorrhizal;
      Saxifraga ferruginea, nonmycorrhizal). Our main objectives were to contrast
      fungal and bacterial successional dynamics and community assembly as well as to
      decouple the effects of plant establishment and time since deglaciation on
      microbial trajectories using high-throughput sequencing. Our data indicate that
      distance from glacier terminus has large effects on biomass accumulation,
      community membership, and distribution for both fungi and bacteria. Surprisingly,
      presence of plants rather than their identity was more important in structuring
      bacterial communities along the chronosequence and played only a very minor role
      in structuring the fungal communities. Further, our analyses suggest that
      bacterial communities may converge during assembly supporting determinism,
      whereas fungal communities show no such patterns. Although fungal communities
      provided little evidence of convergence in community structure, many taxa were
      nonrandomly distributed across the glacier foreland; similar taxon-level
      responses were observed in bacterial communities. Overall, our data highlight
      differing drivers for fungal and bacterial trajectories during early primary
      succession in recently deglaciated soils. 

PMID- 24112460
TI  - Post-marketing surveillance in the published medical and grey literature for
      percutaneous transluminal coronary angioplasty catheters: a systematic review.
AB  - BACKGROUND: Post-marketing surveillance (PMS) may identify rare serious incidents
      or adverse events due to the long-term use of a medical device, which was not
      captured in the pre-market process. Percutaneous transluminal coronary
      angioplasty (PTCA) is a non-surgical procedure that uses a balloon-tipped
      catheter to enlarge a narrowed artery. In 2011, 1,942 adverse event reports
      related to the use of PTCA catheters were submitted to the FDA by the
      manufacturers, an increase from the 883 reported in 2008. The primary research
      objective is to conduct a systematic review of the published and grey literature
      published between 2007 and 2012 for the frequency of incidents, adverse events
      and malfunctions associated with the use of PTCA catheters in patients with
      coronary artery disease (CAD). Grey literature has not been commercially
      published. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled Trials and PubMed for medical literature on PMS for PTCA catheters in
      patients with CAD published between January 2007 and July 2012. We also searched
      the grey literature. RESULTS: This review included 11 studies. The in-hospital
      adverse events reported were individual cases of myocardial infarction and
      hematoma. In studies of patients with coronary perforation, more patients with
      balloon angioplasty were identified compared with patients who required stenting.
      CONCLUSIONS: Our systematic review illustrates that the volume and quality of PMS
      studies associated with the use of PTCA catheters in patients with CAD are low in
      the published and grey literature, and may not be useful sources of information
      for decisions on safety. In most studies, the objectives were not to monitor the
      long-term safety of the use of PTCA catheters in clinical practice. Future
      studies can explore the strengths and limitations of PMS databases administered
      by regulatory authorities.

PMID- 24112461
TI  - Competition in the German pharmacy market: an empirical analysis.
AB  - BACKGROUND: Pharmaceutical products are an important component of expenditure on
      public health insurance in the Federal Republic of Germany. For years, German
      policy makers have regulated public pharmacies in order to limit the increase in
      costs. One reform has followed another, main objective being to increase
      competition in the pharmacy market. It is generally assumed that an increase in
      competition would reduce healthcare costs. However, there is a lack of empirical
      proof of a stronger orientation of German public pharmacies towards competition
      thus far. METHODS: This paper analyses the self-perceptions of owners of German
      public pharmacies and their orientation towards competition in the pharmacy
      markets. It is based on a cross-sectional survey (N = 289) and distinguishes
      between successful and less successful pharmacies, the location of the pharmacies
      (e.g. West German States and East German States) and the gender of the pharmacy
      owner. The data are analysed descriptively by survey items and employing
      bivariate and structural equation modelling. RESULTS: The analysis reveals that
      the majority of owners of public pharmacies in Germany do not currently perceive
      very strong competitive pressure in the market. However, the innovativeness of
      the pharmacist is confirmed as most relevant for net revenue development and the
      profit margin. Some differences occur between regions, e.g. public pharmacies in
      West Germany have a significantly higher profit margin. CONCLUSIONS: This study
      provides evidence that the German healthcare reforms aimed at increasing the
      competition between public pharmacies in Germany have not been completely
      successful. Many owners of public pharmacies disregard instruments of active
      customer-orientated management (such as customer loyalty or an offensive position
      and economies of scale), which could give them a competitive advantage. However,
      it is clear that those pharmacists who strive for systematic and innovative
      management and adopt an offensive and competitive stance are quite successful.
      Thus, pharmacists should change their attitude and develop a more professional
      business model.

PMID- 24112462
TI  - Primary immunodeficiency in Japan; epidemiology, diagnosis, and pathogenesis.
AB  - Primary immunodeficiency (PID) constitutes a large group of diseases, including
      almost 180 hereditary disorders. The patients show susceptibility to various
      infections due to congenital defects of the immune system. It is also known that
      PID patients suffer from non-infectious complications, including autoimmune
      diseases and malignant disorders. During the last 20 years the number of known
      PID has increased considerably. New PID conferring a specific predisposition to
      infections with one or a few pathogens have been described. Disorders of innate
      immunity and various autoinflammatory disorders were included in new categories.
      In contrast, the incidence, clinical manifestations, and genetic factors of PID
      seem to be different among countries or races. The clinical manifestations can
      differ depending on the hygiene conditions, health-care environment, and
      vaccination policy, and so on. A nationwide survey on PID patients in Japan
      provided a lot of information regarding these issues, and it uncovered a
      previously unknown complication of PID, endocrine disorders. In this review, the
      data concerning epidemiology and clinical characteristics of PID in Japan
      obtained in the nationwide questionnaire survey, and the results of studies on
      the clinical and genetic characteristics of Japanese patients with Mendelian
      susceptibility to mycobacterial disease and interleukin-1 receptor-associated
      kinase 4 deficiency are presented in the light of their pathogenesis and
      pathophysiology. 

PMID- 24112463
TI  - Minimally invasive transapical aortic valve implantation and simultaneous major
      pulmonary resection.
AB  - We report a 71-year-old male who underwent successful minimally invasive
      transapical aortic valve implantation to treat severe aortic stenosis, with
      simultaneous pulmonary resection for the treatment of lung cancer. At five-year
      follow-up the patient remains free of symptoms (NYHA I) and recurrence.

PMID- 24112464
TI  - [Commentaries about "Scientific presentations and publications in Radiologia:
      keys and advice for preparation"].

PMID- 24112465
TI  - Investigation of peptide splicing using two-peptide-chain analogs of trypsin
      inhibitor SFTI-1.
AB  - This study examines peptide splicing catalyzed by serine proteinases. A series of
      two-peptide-chain analogs of trypsin inhibitor SFTI-1 were designed and
      synthesized via the solid-phase method. All consisted of two peptide chains (also
      called N- and C-terminal fragments) joined together by one disulfide bridge. The
      analogs were incubated with bovine beta-trypsin or bovine alpha-chymotrypsin.
      Analysis of MS data analysis showed that, after enzyme-catalyzed degradation of
      the single peptide bond between the Lys and Ser residues located at the C
      terminus of the C-terminal peptide chain, a new peptide bond was formed. This
      bond brought together the separated peptide chains, and, as a result, monocyclic
      SFTI-1 was recovered. This proteolytic route of peptide rearrangement appears to
      be similar to peptide splicing catalyzed by proteasomes. However, the proteasome
      is much more complex than 'classical' serine proteinases. 

PMID- 24112466
TI  - A new gamboge derivative compound 2 inhibits cancer stem-like cells via
      suppressing EGFR tyrosine phosphorylation in head and neck squamous cell
      carcinoma.
AB  - Cancer stem-like cells represent a population of tumour-initiating cells that
      lead to the relapse and metastasis of cancer. Conventional anti-cancer
      therapeutic drugs are usually ineffective in eliminating the cancer stem-like
      cells. Therefore, new drugs or therapeutic methods effectively targeting cancer
      stem-like cells are in urgent need to successfully cure cancer. Gamboge is a
      natural anti-cancer medicine whose pharmacological effects are different from
      those of conventional chemotherapeutical drugs and they can kill some kinds of
      cancer cells selectively. In this study, we identified a new gamboge derivative,
      Compound 2 (C2), which presents eminent suppression effects on cancer cells.
      Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the
      growth of both cancer stem-like cells and non-cancer stem-like cells derived from
      head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour
      spheres and colony in vitro, resulting in the loss of expression of multiple
      cancer stem cell (CSC)-related molecules in HNSCC. Treating with C2 effectively
      inhibited the growth of HNSCC in BALB/C nude mice. Further investigation found
      that C2 notably inhibits the activation of epithelial growth factor receptor and
      the phosphorylation of its downstream protein kinase homo sapiens v-akt murine
      thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of
      multiple CSC-related molecules in HNSCC. Our study has demonstrated that C2
      effectively inhibits the stem-like property of cancer stem-like cells in HNSCC
      and may be a hopeful targeting drug in cancer therapy. 

PMID- 24112467
TI  - Plant genome editing made easy: targeted mutagenesis in model and crop plants
      using the CRISPR/Cas system.
AB  - Targeted genome engineering (also known as genome editing) has emerged as an
      alternative to classical plant breeding and transgenic (GMO) methods to improve
      crop plants. Until recently, available tools for introducing site-specific double
      strand DNA breaks were restricted to zinc finger nucleases (ZFNs) and TAL
      effector nucleases (TALENs). However, these technologies have not been widely
      adopted by the plant research community due to complicated design and laborious
      assembly of specific DNA binding proteins for each target gene. Recently, an
      easier method has emerged based on the bacterial type II CRISPR (clustered
      regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) immune
      system. The CRISPR/Cas system allows targeted cleavage of genomic DNA guided by a
      customizable small noncoding RNA, resulting in gene modifications by both non
      homologous end joining (NHEJ) and homology-directed repair (HDR) mechanisms. In
      this review we summarize and discuss recent applications of the CRISPR/Cas
      technology in plants. 

PMID- 24112468
TI  - HIV-1 drug resistance prevalence, drug susceptibility and variant
      characterization in the Jacobi Medical Center paediatric cohort, Bronx, NY, USA.
AB  - OBJECTIVES: With the advent of combined antiretroviral therapy (cART),
      perinatally HIV-infected children are surviving into adolescence and beyond.
      However, drug resistance mutations (DRMs) compromise viral control, affecting the
      long-term effectiveness of ART. The aims of this study were to detect and
      identify DRMs in a HIV-1 infected paediatric cohort. METHODS: Paired plasma and
      dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected
      patients attending the Jacobi Medical Center, New York, USA. Clinical,
      virological and immunological data for these patients were analysed. HIV-1 pol
      sequences were generated from samples to identify DRMs according to the
      International AIDS Society (IAS) 2011 list. RESULTS: Forty-seven perinatally
      infected patients were selected, with a median age of 17.7 years, of whom 97.4%
      were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL
      and a mean CD4 count of 486 cells/MUL at the time of sampling. Nineteen patients
      (40.4%) had achieved undetectable viraemia (< 50 copies/mL) and 40.5% had a CD4
      count of > 500 cells/MUL. Most of the patients (97.9%) had received cART,
      including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM
      prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase
      inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors
      (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs
      to at least one drug class and 5.4% were triple resistant. The mean nucleotide
      similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles
      were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were
      detected in plasma and 26 in DBSs, with 23 present in both. CONCLUSIONS: Although
      more perinatally HIV-1-infected children are reaching adulthood as a result of
      advances in cART, our study cohort presented a high prevalence of resistant
      viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM
      detection.

PMID- 24112469
TI  - Magnetic resonance imaging appearances in primary and secondary angiosarcoma of
      the breast.
AB  - Angiosarcomas are malignant tumours of endovascular origin. They are rare tumours
      accounting for 0.04-1% of all breast malignancies. Two different forms are
      described: primary, occurring in young women, and secondary angiosarcoma, which
      occurs in older women with a history of breast-conserving surgery and radiation
      therapy. Imaging findings on mammography and ultrasound are non-specific, but
      magnetic resonance imaging with dynamic contrast enhancement is more informative.
      We present two cases - one of primary and one of secondary angiosarcoma - and
      review the imaging findings. 

PMID- 24112470
TI  - Red blood cell distribution width is associated with incidence of atrial
      fibrillation.
AB  - OBJECTIVES: Red blood cell distribution width (RDW), a measure of variation in
      erythrocyte volume, has been associated with several cardiovascular disorders,
      but the relationship with atrial fibrillation (AF) remains unclear. We
      investigated the association between RDW and incidence of first hospitalization
      due to AF in a population-based cohort. DESIGN: Red blood cell distribution width
      was measured in 27,124 subjects from the general population (age 45-73 years, 62%
      women) with no history of AF, heart failure, myocardial infarction or stroke. The
      association between baseline RDW and incidence of AF identified from the Swedish
      Hospital Discharge Register was evaluated. RESULTS: During a mean follow-up of
      13.6 years, 1894 subjects (53% men) were hospitalized with a diagnosis of AF.
      After adjustment for potential confounding factors, including cardiovascular
      disease risk factors, nutrient intake (iron, vitamin B12 and folate) and several
      haematological parameters (haemoglobin concentration, mean corpuscular volume and
      corpuscular haemoglobin content), the hazard ratio (HR) for incidence of AF was
      1.33 [95% confidence interval (CI) 1.16-1.53] for the fourth versus first
      quartile of RDW (P for trend <0.001). The results were essentially unchanged when
      subjects with incident myocardial infarction or hospitalizations because of heart
      failure were censored from the analysis (HR 1.30, 95% CI 1.13-1.51; P for trend =
      0.001). CONCLUSION: Red blood cell distribution width was associated with
      incidence of AF independently of several cardiovascular, nutritional and
      haematological factors in this study of middle-aged subjects from the general
      population.

PMID- 24112472
TI  - Self-assessment of genital anatomy and sexual function within a Belgian, Dutch
      speaking female population: a validation study.
AB  - INTRODUCTION: Data on self-perceived genital anatomy and sensitivity should be
      part of the long-term follow-up of genitoplasty procedures. However, no normative
      data, based on a large sample, exist to date. AIMS: Validation of the Self
      Assessment of Genital Anatomy and Sexual Function, Female version (SAGAS-F)
      questionnaire within a Belgian, Dutch-speaking female population. METHODS: Seven
      hundred forty-nine women with no history of genital surgery (aged 18-69 years,
      median 25 years) completed an Internet-based survey of whom 21 women underwent a
      gynecological examination as to correlate self-reported genital sensitivity
      assessed in an experimental setting. MAIN OUTCOME MEASURES: The SAGAS-F enables
      women to rate the sexual pleasure, discomfort, intensity of orgasm, and effort
      required for achieving orgasm in specified areas around the clitoris and within
      the vagina, as well as genital appearance. The latter was similarly evaluated by
      an experienced gynecologist, and women were asked to functionally rate the
      anatomical areas pointed out with a vaginal swab. RESULTS: Sexual pleasure and
      orgasm were strongest, and effort to attain orgasm and discomfort was lowest when
      stimulating the clitoris and sides of the clitoris (P < 0.05). Vaginal
      sensitivity increased with increasing vaginal depth, but overall orgasmic
      sensitivity was lower as compared with the clitoris. Functional scores on the
      SAGAS-F and during gynecological examination corresponded highly on most
      anatomical areas (P < 0.05). Gynecologist's ratings corresponded highly with the
      women's ratings for vaginal size (90%) but not for clitoral size (48%).
      CONCLUSIONS: Replication of the original pilot study results support the validity
      of the questionnaire. The SAGAS-F discriminates reasonably well between various
      genital areas in terms of erotic sensitivity. The clitoris itself appeared to be
      the most sensitive, consistent with maximum nerve density in this area. Surgery
      to the clitoris could disrupt neurological pathways and compromise erotic
      sensation and pleasure.

PMID- 24112471
TI  - EphA2 signaling following endocytosis: role of Tiam1.
AB  - Eph receptors and their membrane-bound ligands, the ephrins, represent a complex
      subfamily of receptor tyrosine kinases (RTKs). Eph/ephrin binding can lead to
      various and opposite cellular behaviors such as adhesion versus repulsion, or
      cell migration versus cell-adhesion. Recently, Eph endocytosis has been
      identified as one of the critical steps responsible for such diversity. Eph
      receptors, as many RTKs, are rapidly endocytosed following ligand-mediated
      activation and traffic through endocytic compartments prior to degradation.
      However, it is becoming obvious that endocytosis controls signaling in many
      different manners. Here we showed that activated EphA2 are degraded in the
      lysosomes and that about 35% of internalized receptors are recycled back to the
      plasma membrane. Our study is also the first to demonstrate that EphA2 retains
      the capacity to signal in endosomes. In particular, activated EphA2 interacted
      with the Rho family GEF Tiam1 in endosomes. This association led to Tiam1
      activation, which in turn increased Rac1 activity and facilitated Eph/ephrin
      endocytosis. Disrupting Tiam1 function with RNA interference impaired both
      ephrinA1-dependent Rac1 activation and ephrinA1-induced EphA2 endocytosis. In
      summary, our findings shed new light on the regulation of EphA2 endocytosis,
      intracellular trafficking and signal termination and establish Tiam1 as an
      important modulator of EphA2 signaling. 

PMID- 24112473
TI  - FOXO/TXNIP pathway is involved in the suppression of hepatocellular carcinoma
      growth by glutamate antagonist MK-801.
AB  - BACKGROUND: Accumulating evidence has suggested the importance of glutamate
      signaling in cancer growth, yet the signaling pathway has not been fully
      elucidated. N-methyl-D-aspartic acid (NMDA) receptor activates intracellular
      signaling pathways such as the extracellular-signal-regulated kinase (ERK) and
      forkhead box, class O (FOXO). Suppression of lung carcinoma growth by NMDA
      receptor antagonists via the ERK pathway has been reported. However, series of
      evidences suggested the importance of FOXO pathways for the regulation of normal
      and cancer cell growth. In the liver, FOXO1 play important roles for the cell
      proliferation such as hepatic stellate cells as well as liver metabolism. Our aim
      was to investigate the involvement of the FOXO pathway and the target genes in
      the growth inhibitory effects of NMDA receptor antagonist MK-801 in human
      hepatocellular carcinoma. METHODS: Expression of NMDAR1 in cancer cell lines from
      different tissues was examined by Western blot. NMDA receptor subunits in HepG2,
      HuH-7, and HLF were examined by reverse transcriptase polymerase chain reaction
      (RT-PCR), and growth inhibition by MK-801 and NBQX was determined using the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      effects of MK-801 on the cell cycle were examined by flow cytometry and Western
      blot analysis. Expression of thioredoxin-interacting protein (TXNIP) and p27 was
      determined by real-time PCR and Western blotting. Activation of the FOXO pathway
      and TXNIP induction were examined by Western blotting, fluorescence microscopy,
      Chromatin immunoprecipitation (ChIP) assay, and reporter gene assay. The effects
      of TXNIP on growth inhibition were examined using the gene silencing technique.
      RESULTS: NMDA receptor subunits were expressed in all cell lines examined, and MK
      801, but not NBQX, inhibited cell growth of hepatocellular carcinomas. Cell cycle
      analysis showed that MK-801 induced G1 cell cycle arrest by down-regulating
      cyclin D1 and up-regulating p27. MK-801 dephosphorylated Thr24 in FOXO1 and
      induced its nuclear translocation, thus increasing transcription of TXNIP, a
      tumor suppressor gene. Knock-down of TXNIP ameliorated the growth inhibitory
      effects of MK-801. CONCLUSIONS: Our results indicate that functional NMDA
      receptors are expressed in hepatocellular carcinomas and that the FOXO pathway is
      involved in the growth inhibitory effects of MK-801. This mechanism could be
      common in hepatocellular carcinomas examined, but other mechanisms such as ERK
      pathway could exist in other cancer cells as reported in lung carcinoma cells.
      Altered expression levels of FOXO target genes including cyclin D1 and p27 may
      contribute to the inhibition of G1/S cell cycle transition. Induction of the
      tumor suppressor gene TXNIP plays an important role in the growth inhibition by
      MK-801. Our report provides new evidence that FOXO-TXNIP pathway play a role in
      the inhibition of the hepatocellular carcinoma growth by MK-801.

PMID- 24112475
TI  - Heart rate variability and procedural outcome in catheter ablation for atrial
      fibrillation.
AB  - INTRODUCTION: In patients with normal hearts, increased vagal tone is associated
      with onset of paroxysmal atrial fibrillation (AF). Vagal denervation of the atria
      renders AF less inducible. Circumferential pulmonary vein isolation (CPVI) is
      effective for treating paroxysmal and persistent AF, and has been shown to impact
      heart rate variability (HRV) indices, in turn, reflecting vagal denervation. We
      examined the impact of CPVI on HRV indices, and evaluated the relationship
      between vagal modification and AF recurrence. METHODS: Electrocardiogram
      recordings were collected from 83 consecutive patients (63 male, 20 female, age
      56.9 +/- 9.3 years) undergoing CPVI for paroxysmal (n = 56) or persistent (n =
      27) AF. Recordings were obtained over 10 minutes preprocedure, and at intervals
      up to 12 months. Antiarrhythmic medications were suspended prior to CPVI, and
      were resumed for 3 months following. Success was defined as no recurrence of
      atrial arrhythmia lasting longer than 30 seconds. RESULTS: In patients with
      successful procedures (n = 56, 42 paroxysmal, 14 persistent), HRV indices were
      significantly altered, with respect to preprocedure levels, over a sustained
      period. However, patients with recurrence (n = 27, 14 paroxysmal, 13 persistent)
      demonstrated similar HRV to their preprocedure levels over the follow-up period.
      CONCLUSION: Our results suggest that patients experiencing recurrence after a
      single CPVI have HRV attenuated by the procedure only intermittently, whereas
      patients with one successful CPVI experience a sustained change. A short-term HRV
      recording is a convenient and potentially important marker for recurrence of
      atrial arrhythmia in a population undergoing CPVI.

PMID- 24112476
TI  - Sweat hypersensitivity-induced urticaria and sebaceous adenitis in an American
      Saddlebred.

PMID- 24112474
TI  - Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome
      stability and adaptive radiation.
AB  - BACKGROUND: Lyme disease is caused by spirochete bacteria from the Borrelia
      burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the
      evolution of B. burgdorferi s.l. and identify the genomic basis of its human
      virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe
      and the United States, including B. burgdorferi sensu stricto (B. burgdorferi
      s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. "bavariensis" (1), B.
      spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. "finlandensis" (1).
      RESULTS: Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were
      obtained using genome-wide single-nucleotide polymorphisms, despite
      recombination. Phylogeny-based pan-genome analysis showed that the rate of gene
      acquisition was higher between species than within species, suggesting adaptive
      speciation. Strong positive natural selection drives the sequence evolution of
      lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded
      ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer
      simulations predicted rapid adaptive radiation of genomic groups as population
      size increases. CONCLUSIONS: Intra- and inter-specific pan-genome sizes of B.
      burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene
      acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial
      pathogens, resulting in high genome stability and few lineage-specific genes.
      Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number
      and sequence variations of lipoprotein genes. New genomic groups are likely to
      emerge if the current trend of B. burgdorferi s.l. population expansion
      continues.

PMID- 24112477
TI  - Flow cytometry-based enrichment for cell shape mutants identifies multiple genes
      that influence Helicobacter pylori morphology.
AB  - The helical cell shape of Helicobacter pylori is highly conserved and contributes
      to its ability to swim through and colonize the viscous gastric mucus layer. A
      multi-faceted peptidoglycan (PG) modification programme involving four recently
      characterized peptidases and two accessory proteins is essential for maintaining
      H. pylori's helicity. To expedite identification of additional shape-determining
      genes, we employed flow cytometry with fluorescence-activated cell sorting (FACS)
      to enrich a transposon library for bacterial cells with altered light scattering
      profiles that correlate with perturbed cell morphology. After a single round of
      sorting, 15% of our clones exhibited a stable cell shape defect, reflecting 37
      fold enrichment. Sorted clones with straight rod morphology contained insertions
      in known PG peptidases, as well as an insertion in csd6, which we demonstrated
      has ld-carboxypeptidase activity and cleaves monomeric tetrapeptides in the PG
      sacculus, yielding tripeptides. Other mutants had only slight changes in helicity
      due to insertions in genes encoding MviN/MurJ, a protein possibly involved in
      initiating PG synthesis, and the hypothetical protein HPG27_782. Our findings
      demonstrate FACS robustly detects perturbations of bacterial cell shape and
      identify additional PG peptide modifications associated with helical cell shape
      in H. pylori. 

PMID- 24112479
TI  - Appendix viriliformis: an intra-abdominal testis and an appendicoileal fistula.
AB  - When a patient is taken to theatre for a laparotomy, surprises can still be found
      despite modern investigative techniques. We present the case of two rare
      abdominal pathologies (an appendicoileal fistula and an intra-abdominal testis
      adherent to the vermiform appendix) being found simultaneously and review the
      literature on these topics. 

PMID- 24112478
TI  - Chronic sublethal stress causes bee colony failure.
AB  - Current bee population declines and colony failures are well documented yet
      poorly understood and no single factor has been identified as a leading cause.
      The evidence is equivocal and puzzling: for instance, many pathogens and
      parasites can be found in both failing and surviving colonies and field pesticide
      exposure is typically sublethal. Here, we investigate how these results can be
      due to sublethal stress impairing colony function. We mathematically modelled
      stress on individual bees which impairs colony function and found how positive
      density dependence can cause multiple dynamic outcomes: some colonies fail while
      others thrive. We then exposed bumblebee colonies to sublethal levels of a
      neonicotinoid pesticide. The dynamics of colony failure, which we observed, were
      most accurately described by our model. We argue that our model can explain the
      enigmatic aspects of bee colony failures, highlighting an important role for
      sublethal stress in colony declines. 

PMID- 24112480
TI  - Back to basics: iatrogenic intravenous cannula embolus.
AB  - We present a case of distal venous embolisation of a peripheral intravenous
      cannula tip that had lost its structural integrity through repeated failed
      attempts of insertion of the same cannula, contrary to protocols for intravenous
      access. Radiological imaging confirmed the presence of a foreign body in the
      middle finger and the patient was brought to theatre. A 2.2cm long catheter tube
      was removed via a venotomy from the dorsal digital vein. 

PMID- 24112481
TI  - An internal carotid artery aneurysm presenting with dysarthria.
AB  - A 72-year-old woman presented to her general practitioner with a 4-week history
      of right neck swelling. Clinical examination elicited a pulsatile mass consistent
      with a carotid artery aneurysm. Five days later the patient noticed her tongue
      movements had become awkward with associated dysarthria. Computed tomography
      confirmed a 4cm internal carotid artery aneurysm arising just distally to the
      carotid bifurcation. She proceeded to transfemoral diagnostic carotid
      angiography. Balloon occlusion of the right internal carotid artery origin was
      performed for a ten-minute period without any neurological deficit. The decision
      was taken to proceed to surgical ligation of the origin of the internal carotid
      artery. Her symptoms of dysarthria have resolved. 

PMID- 24112482
TI  - Chronic wound and postamputation claudication pain in a diabetic patient.
AB  - Underlying ischaemic disease should be excluded in patients with delayed wound
      healing. Contrast angiography is a useful imaging method for assessing the
      specific cause of wound chronicity and may also be helpful in assessing the
      aetiology of unexplained pain symptoms. Angioplasty provides a practical
      alternative to more invasive techniques in addressing peripheral ischaemia. Our
      patient suffered claudication-type pain in his thigh and a non-healing stump
      wound following below-knee amputation. Magnetic resonance angiography confirmed
      the presence of arterial stenoses and an angioplasty was successfully performed
      to improve patency of the profunda femoris vessel. Following the operation, the
      claudication pain symptoms were significantly reduced and the stump wound went on
      to heal. 

PMID- 24112483
TI  - Bilothorax as a rare sign of intra-abdominal bile leak in a patient without
      peritonitis.
AB  - We present the case of a 60-year-old patient who developed a right-sided
      bilothorax following para-aortic lymph node sampling. Bilothorax is a very rare
      condition, with most of the reported cases resulting from direct flow of bile
      from the biliary system to the pleural space through a fistula or other defect in
      the diaphragm. In this case, there was no obvious communication found between
      peritoneal and pleural spaces. Our patient proceeded to an exploratory laparotomy
      following this finding in the absence of peritonitis. Bilothorax should be
      considered in patients who develop a progressive pleural effusion following upper
      gastrointestinal surgery, particularly if it involves manipulation of the biliary
      system. 

PMID- 24112484
TI  - Spontaneous transanal evisceration.
AB  - Spontaneous rectal rupture with subsequent transanal evisceration is an unusual
      phenomenon that has been rarely reported in the literature. Owing to its
      infrequent occurrence, little is known about the aetiology of this event although
      a weakening of the anterior rectal wall has been proposed. This article describes
      the first reported case of spontaneous transanal evisceration occurring in a
      patient with chronic lymphocytic leukaemia. 

PMID- 24112485
TI  - Gastric outlet obstruction with an elevated serum pancreatic lipase secondary to
      an infraumbilical hernia.
AB  - We report the case of a 68-year-old woman who presented with symptoms and signs
      of gastric outlet obstruction with a history of a ventral hernia. Clinical
      examination revealed a large ventral hernia with visible peristalsis of the
      herniated viscera. Initial serum biochemistry revealed a markedly elevated lipase
      level and deranged renal function. Computed tomography demonstrated an
      infraumbilical hernia with herniation of the stomach through the ventral defect
      and distortion of the pancreatic anatomy. The hernia was reduced operatively and
      repaired, leading to an uneventful recovery. 

PMID- 24112486
TI  - Perforated sigmoid colon carcinoma in an irreducible inguinoscrotal hernia.
AB  - Inguinal (inguinoscrotal) hernia and colon cancer are common conditions. However,
      it is rare for primary colon cancer to exist in an inguinal hernia sac and even
      rarer for it to perforate. We report such an event in our patient, who had an
      irreducible left inguinoscrotal hernia containing a sigmoid colon carcinoma that
      had perforated. This clinical picture can be easily confused with hernia
      strangulation unless the clinician is alert to the presence of certain sinister
      symptoms and signs. 

PMID- 24112487
TI  - Successful surgical repair of acute type A aortic dissection without the use of
      blood products.
AB  - We report successful surgical treatment of type A aortic dissection in a
      Jehovah's Witness without the use of any blood products. An interposition graft
      replacement of the ascending aorta was carried out. This was under right axillo
      atrial cardiopulmonary bypass with antegrade cerebral perfusion via right a
      subclavian and left carotid cannula for 24 minutes at 28 degrees C. Body
      temperature was kept at 32 degrees C throughout. Autologous transfusion was
      deployed using cell salvage and a preoperative haemodilution technique. The
      patient was given tranexamic acid, desmopressin, recombinant factor VIIa, folic
      acid and epoetin alfa. Patients who object to transfusion represent a significant
      challenge, especially those who are at a high risk of coagulopathy associated
      with inherent aortic dissection leading to perturbed haemodynamics,
      cardiopulmonary bypass and hypothermic circulatory arrest. Type A aortic
      dissection repair is possible in patients refusing the use of blood products with
      blood salvage techniques and synthetic products that can limit the risk of
      bleeding. Minimal hypothermia is vital to preserve platelet function and avoid
      coagulopathy. Thus, a combination of normothermic/minimal hypothermia and
      antegrade cerebral protection with a blood conservation strategy can be deployed
      for a successful surgical outcome in aortic dissection without transfusion. 

PMID- 24112488
TI  - Streptococcal toxic shock syndrome following total thyroidectomy.
AB  - Group A streptococcal toxic shock syndrome following clean surgery is a rare
      occurrence. Its incidence following thyroid surgery has not been described in the
      literature. We report on the presentation and management of severe streptococcal
      toxic shock syndrome following a total thyroidectomy for a multinodular goitre in
      a patient with Cowden syndrome. This report presents an overview of streptococcal
      toxic shock syndrome with a focus on the management issues to consider so as to
      improve patient outcome. All surgeons must maintain a high index of suspicion for
      this rare but dangerous entity. 

PMID- 24112489
TI  - Operative strategy for fistula-in-ano without division of the anal sphincter.
AB  - INTRODUCTION: The treatment of perianal fistulas is diverse because no single
      technique is universally effective. Fistulotomy remains the most effective way of
      eradicating the pathology but it renders the patient at some risk of faecal
      incontinence, which many patients are reluctant to take. There are no data in the
      literature to indicate the healing rate of perianal fistulas when using an
      operative strategy that routinely avoids division of any part of the anal
      sphincter. The aim of this paper is to present the long-term results with an
      operative strategy that aims to avoid division of any part of the anal sphincter
      complex when treating all types of perianal fistulas, thereby
      minimising/eliminating the risk of postoperative incontinence. METHODS: We report
      54 consecutive cases of anal fistula that presented electively and as an
      emergency. Patients with known or subsequently diagnosed inflammatory bowel
      disease or malignancy were excluded from the study. RESULT: Overall, 46 patients
      (37 male and 9 female) with a median age at presentation of 42 years (range: 19
      73 years) were treated by lay-open of the subcutaneous tract of the perianal
      fistula and insertion of a loose seton for the part of the fistula tract related
      to the sphincter complex. The types of fistula treated were intersphincteric
      (89%), transsphincteric (4%) and high suprasphincteric (7%). The median length of
      time that the seton was left in place was 7 months (range: 1.5-24 months). The
      healing rate was 86% with a recurrence rate of 19% and a median follow-up
      duration of 42 months. CONCLUSIONS: Patients who are reluctant to take any risk
      of faecal incontinence could be treated using an operative strategy that
      routinely avoids division of any part of the anal sphincter complex as this has a
      recurrence rate that compares well with other treatment modalities.

PMID- 24112490
TI  - Comparison of clinical outcomes of open, laparoscopic and single port
      appendicectomies.
AB  - INTRODUCTION: Appendicectomy is the most common surgical procedure performed in
      general surgery. This study aimed to compare the outcomes of open appendicectomy
      (OA), laparoscopic appendicectomy (LA) and single port laparoscopic
      appendicectomy (SPLA). METHODS: Fifty consecutive patients with suspected acute
      appendicitis were studied (OA: n=20, LA: n=20, SPLA: n=10). Clinical outcomes
      were compared between the three groups in terms of operative time, blood loss,
      postoperative complications, length of hospital stay and cost. RESULTS: Patient
      demographics were similar among groups (p>0.05). SPLA was characterised by longer
      operative time (88.1 minutes vs 35.6 minutes in OA and 33.4 minutes in LA) and
      higher costs (12.84 thousand Chinese yuan [RMB] vs 8.41 thousand RMB in LA and
      4.99 thousand RMB in OA). OA was characterised by more blood loss (9.8ml vs 7.5ml
      in SPLA and 6.8ml in LA), longer hospital stay (7.5 days vs 3.5 days in LA and
      3.4 days in SPLA) and lower costs. The total number of complications was higher
      for OA (n=2) than for LA and SPLA (n=0) although this was not statistically
      significant. CONCLUSIONS: Where feasible, LA should be undertaken as the initial
      treatment of choice for most cases of suspected appendicitis.

PMID- 24112491
TI  - The performance of routine computed tomography for the detection of colorectal
      cancer.
AB  - INTRODUCTION: Although colonoscopy and computed tomography (CT) colonography in
      expert hands are the most sensitive investigations for colorectal cancer, some
      patients may not tolerate the necessary bowel preparation and insufflation of gas
      into the colon. We assessed the performance of unprepared contrast CT for the
      detection of colorectal cancer. METHODS: A retrospective review was undertaken of
      all patients who had contrast CT of the abdomen and pelvis and then went on to
      have colonoscopy at our institutions between 2007 and 2010. RESULTS: Overall, 96
      patients were identified as having had CT prior to colonoscopy. The sensitivity
      of CT in detecting colorectal cancer was 100% (95% confidence interval [CI]: 19.8
      100%) and the specificity was 95.7% (95% CI: 88.8-98.6%). The positive predictive
      value was 33.3% (95% CI: 6.0-75.9%) and the negative predictive value was 100%
      (95% CI: 94.8-100%). CONCLUSIONS: Non-targeted CT that is negative for colorectal
      malignancy is usually reassuring but the decision for further investigations
      should be made on a case-by-case basis, taking into account of the likelihood of
      underlying colorectal malignancy and the underlying co-morbidities of the
      patient. However, video colonoscopy is usually necessary to assess positive CT
      findings.

PMID- 24112492
TI  - Variability in management of T1 colorectal cancer in Wales.
AB  - INTRODUCTION: The management of T1 colorectal cancer is controversial. Surgical
      resection should offer cure in the majority of patients and can stage lymph nodes
      accurately. Nevertheless, there can be significant associated morbidity and it
      potentially risks overtreating the patient. Endoscopic/local excision has
      significantly reduced morbidity but risks undertreating undetected metastatic
      lymph nodes, thereby compromising oncological outcomes. The aim of this study was
      to review the practice across Wales over a two-year period. METHODS: Data on T1
      tumours for the period of 2009-2011 were collected from the Cancer Network
      Information System Cymru. RESULTS: A total of 161 patients were diagnosed as
      having T1 colorectal cancer (without prior neoadjuvant treatment). The median age
      was 68 years (range: 14-91 years) and 66% of the patients were male. Forty-eight
      (30%) of these tumours were screen detected. There were 112 colonic and 49 rectal
      tumours. Ninety-five patients with colonic tumours (85%) underwent major surgical
      resections, 51% of which were laparoscopic. Forty patients with rectal cancers
      (82%) underwent major surgical resection and 45% of these procedures were
      laparoscopic. The rest of the patients underwent local excision in the form of
      endoscopic polypectomy or transanal resection. CONCLUSIONS: This study
      demonstrates that there is no consensus in the management of T1 disease across
      Wales. With the advent of screening and the development of more sophisticated
      endoscopic techniques, the decision of how to treat T1 colorectal cancer will
      become a more regular challenge for the colorectal multidisciplinary team. The
      treatment needs standardisation. For now, however, this balance of risk will need
      to be made on an individual patient basis.

PMID- 24112493
TI  - Minimally invasive direct coronary artery bypass versus off-pump coronary surgery
      through sternotomy.
AB  - INTRODUCTION: Although it is not a new technique, minimally invasive direct
      coronary artery bypass (MIDCAB) is employed only by a few surgeons in the UK. We
      compared our experience with MIDCAB with that of single vessel off-pump coronary
      artery bypass (OPCAB) graft surgery through a standard median sternotomy.
      METHODS: Patients who underwent either MIDCAB or OPCAB between April 2008 and
      July 2011 were reviewed. Exclusion criteria included patients with an ejection
      fraction of <0.5 or previous cardiac surgery. Data were obtained retrospectively
      from our prospective database, medical records and through general practitioners.
      RESULTS: Overall, 74 patients were analysed in the MIDCAB group and 78 in the
      OPCAB group. Their demographics and EuroSCORE (European System for Cardiac
      Operative Risk Evaluation) values were comparable (p>0.05). There was no
      statistically significant difference in the two groups in terms of mortality,
      recurrent myocardial infarction, postoperative stroke, wound infection, atrial
      fibrillation or need for reintervention. The MIDCAB group had six conversions to
      a sternotomy. Eight patients in each group required blood transfusion, with the
      average transfusion being 1.8 units in the MIDCAB group and 3.2 units in the
      OPCAB group. The mean duration of ventilation and intensive care unit stay was
      5.0 hours and 38.4 hours in the MIDCAB group and 5.4 and 47.8 hours in the OPCAB
      group. The mean hospital stay was significantly reduced in the MIDCAB population
      (6.1 vs 8.5 days, p<0.05). CONCLUSIONS: MIDCAB can be performed safely in
      appropriately selected patients with outcomes comparable with OPCAB. The
      potential benefits include shorter hospital stay, reduced need for blood
      transfusion and faster recovery.

PMID- 24112494
TI  - Operative treatment improves patient function in recalcitrant medial
      epicondylitis.
AB  - The purpose of this retrospective study was to assess the outcome of open surgery
      for patients with recalcitrant medial epicondylitis following failed conservative
      management. The clinical results are presented for 15 patients (17 elbows) who
      were reviewed at a mean follow-up of 66 months. Operative treatment improved
      patient function significantly with a mean increase in grip strength of 10kg and
      a mean decrease (improvement) in DASH (Disabilities of the Arm, Shoulder and
      Hand) score of 25.7. All but one patient experienced little or no residual elbow
      discomfort and had excellent Mayo elbow performance scores postoperatively.
      Eleven of the twelve patients who were previously in employment were able to
      return to work within eight weeks of surgery. This study demonstrates that
      operative treatment for recalcitrant medial epicondylitis is effective in
      restoring patient function and strength. 

PMID- 24112495
TI  - Effect of novel vitamin D receptor activator paricalcitol on renal
      ischaemia/reperfusion injury in rats.
AB  - INTRODUCTION: Despite the developments in modern medicine, acute renal injury is
      still a challenging and common health problem. It is well known that ischaemia
      and reperfusion takes place in pathological mechanisms. Efforts to clarify the
      pathophysiology and interventions to improve outcomes are essential. Our study
      aimed to investigate whether the prophylactic use of paricalcitol is beneficial
      in renal ischaemia/reperfusion (I/R) injury. METHODS: Twenty-four Wistar albino
      rats were assigned randomly to four groups. Right nephrectomies were performed at
      the time of renal arterial clamping. Sham surgery was performed on the rats in
      group 1. For the rats in group 2, the left renal artery was clamped for 45
      minutes. The rats in group 3 received paricalcitol for seven days
      (0.2MUg/kg/day); following this, a right nephrectomy and left renal arterial
      clamping were not performed. The rats in group 4 received paricalcitol for seven
      days (0.2MUg/kg/day); following this, a right nephrectomy and left renal arterial
      clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive
      substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric
      oxide metabolites, serum urea and creatinine levels were measured for all four
      groups. RESULTS: In group 4, there were some improvements in terms of TBARS,
      nitrite, nitrate, superoxide dismutase and creatinine levels. In the
      histopathological evaluation, paricalcitol therapy improved tubular necrosis and
      medullar congestion but there was no significant difference in terms of tubular
      cell swelling, cellular vacuolisation or general damage. Immunohistopathological
      examination revealed lower scores for vascular endothelial growth factor in the
      group 4 rats than in group 2. CONCLUSIONS: Paricalcitol therapy improved renal
      I/R injury in terms of serum and histopathological parameters. These potential
      beneficial effects need to be further investigated.

PMID- 24112496
TI  - Trends in orthopaedic antimicrobial prophylaxis in the UK between 2005 and 2011.
AB  - INTRODUCTION: Antimicrobial prophylaxis remains the most powerful tool used to
      reduce infection rates in orthopaedics but the choice of antibiotic is complex.
      The aim of this study was to examine trends in antimicrobial prophylaxis in
      orthopaedic surgery involving the insertion of metalwork between 2005 and 2011.
      METHODS: Two questionnaires (one in 2008 and one in 2011) were sent to all
      National Health Service trusts in the UK using the Freedom of Information Act.
      RESULTS: In total, 87% of trusts that perform orthopaedic surgery responded. The
      use of cefuroxime more than halved between 2005 and 2011 from 80% to 36% and 78%
      to 26% in elective surgery and trauma surgery respectively. Combination therapy
      with flucloxacillin and gentamicin rose from 1% to 32% in elective and 1% to 34%
      in trauma surgery. Other increasingly popular regimes include teicoplanin and
      gentamicin (1% to 10% in elective, 1% to 6% in trauma) and co-amoxiclav (3% to 8%
      in elective, 4% to 14% in trauma). The majority of changes occurred between 2008
      and 2010. Over half (56%) of the trusts stated that Clostridium difficile was the
      main reason for changing regimes. CONCLUSIONS: In 2008 a systematic review
      involving 11,343 participants failed to show a difference in surgical site
      infections when comparing different antimicrobial prophylaxis regimes in
      orthopaedic surgery. Concerns over C difficile and methicillin resistant
      Staphylococcus aureus have influenced antimicrobial regimes in both trauma and
      elective surgery. Teicoplanin would be an appropriate choice for antimicrobial
      prophylaxis in both trauma and elective units but this is not reflected in its
      current level of popularity.

PMID- 24112497
TI  - The role of magnetic resonance cholangiopancreatography in the management of
      acute gallstone pancreatitis.
AB  - INTRODUCTION: The aim of this study was to identify whether magnetic resonance
      cholangiopancreatography (MRCP) can be used selectively in patients with acute
      gallstone pancreatitis to detect choledocholithiasis, based on liver function
      tests (LFTs) and ultrasonography appearance. METHODS: All patients admitted
      between January 2008 and January 2011 with gallstone pancreatitis (amylase
      >300u/l) who underwent MRCP were included in the study. LFTs and radiology
      reports were obtained from the respective computer systems. RESULTS: Overall, 173
      patients with acute gallstone pancreatitis underwent MRCP and 30% (52/173) showed
      choledocholithiasis. The mean bilirubin level was significantly higher in those
      with choledocholithiasis (46 +/-5MUmol/l vs 36 +/-3MUmol/l, p=0.0388) although
      there was no significant difference in alkaline phosphatase (276 +/-25iu/l vs 229
      +/-16iu/l, p=0.1154). However, sensitivity of abnormal bilirubin (>21MUmol/l) for
      choledocholithiasis was only 62% and specificity was 41%. Sensitivity of abnormal
      alkaline phosphatase (>140iu/l) for choledocholithiasis was only 75% and
      specificity was 37%. There was a significant association between biliary
      dilatation on ultrasonography and choledocholithiasis on MRCP (p=0.0099) although
      the sensitivity of biliary dilatation for choledocholithiasis was only 44% and
      the specificity was 79%. Furthermore, there was no difference in the incidence of
      choledocholithiasis on MRCP for those patients with persistently deranged LFTs
      versus those whose LFTs returned to normal (relative risk: 1.07, 95% confidence
      interval: 0.61-1.89, p=1.00). Overall, 10% of patients with choledocholithiasis
      on MRCP had entirely normal LFTs on admission and no biliary dilatation or
      choledocholithiasis on ultrasonography. CONCLUSIONS: All patients with acute
      gallstone pancreatitis should undergo specific imaging, preferably MRCP, to
      exclude choledocholithiasis as LFTs and ultrasonography are inaccurate in
      predicting common bile duct stones.

PMID- 24112498
TI  - Hepatobiliary cystadenomas.
AB  - INTRODUCTION: Hepatobiliary cystadenomas are rare cystic tumours that can arise
      from any portion of the biliary tract but most commonly develop intrahepatically.
      They typically cause non-specific symptoms and are often detected incidentally.
      Cystadenomas can be mistaken for simple hepatic cysts on radiological imaging,
      which leads to inadequate treatment. Hepatobiliary cystadenomas have a malignant
      predisposition and a high recurrence rate. Complete excision including hepatic
      resection is therefore generally recommended. METHODS: Three cases of
      hepatobiliary cystadenoma were identified at one unit over a six-month period.
      Their clinical details and management are reported. RESULTS: Three female
      patients are described aged 25, 37 and 73 years. One patient presented because of
      recurrent infection, one presented because of pressure related symptoms and one
      lesion was identified incidentally. All patients were investigated by
      ultrasonography and computed tomography (CT), two additionally had magnetic
      resonance imaging (MRI) and one had a liver biopsy. The tumours were 4-16cm in
      size and all lesions were excised by non-anatomical, parenchyma sparing
      resections. Histology revealed mixed epithelium with underlying ovarian-like
      stroma. CONCLUSIONS: The management of hepatic cystadenomas as well as operative
      and pathological findings are discussed. Preoperative ultrasonography, CT and MRI
      is recommended, and early referral for specialist hepatobiliary review is
      advised. Operative resection is also recommended and complete excision was
      achieved in these cases. This strategy is supported by the current literature and
      recurrence has been shown to be unlikely.

PMID- 24112499
TI  - Natural history of acalculous biliary symptoms.
AB  - INTRODUCTION: The radiological criteria for the diagnosis of gallbladder disease
      rely largely on the detection of calculi using ultrasonography. Patients may,
      however, suffer symptoms typical of biliary pain without detectable gallstones.
      The aim of this study was to identify a cohort of patients presenting with
      recurrent episodes of biliary symptoms in the absence of identifiable pathology
      on ultrasonography and to record the outcome of subsequent imaging
      investigations. METHODS: Records of patients having abdominal ultrasonography
      during a four-month period in 2006 were accessed retrospectively and those with
      symptoms suggesting biliary disease were identified. Radiology records were
      reviewed over a five-year follow-up period to identify patients undergoing
      further imaging for recurrent biliary symptoms and outcomes were recorded.
      RESULTS: A total of 512 patients had ultrasonography for investigation of
      symptoms consistent with biliary disease. Almost half (41.2%) of these were found
      to have gallbladder pathology on ultrasonography and 4.7% of patients went on to
      have further investigations for similar symptoms without achieving a diagnosis.
      The median age of this group was 47 years and 75% of these patients were female.
      During the follow-up period, 2.6% of patients with biliary symptoms and initially
      normal ultrasonography developed gallstones and in 1.3% pancreatitis was
      demonstrated on imaging. CONCLUSIONS: A small minority of patients who present
      with biliary symptoms and have no abnormality on ultrasonography present with
      recurrent symptoms or develop significant biliary pathology. These patients
      should be identified by interview at routine follow-up visits and further
      investigations should be considered.

PMID- 24112500
TI  - Variations in selective nerve root block technique.
AB  - INTRODUCTION: Much literature reports on selective nerve root blocks (SNRBs) in
      cases of lumbosacral radiculopathy. Unfortunately, authors only inconsistently
      reveal the exact needle tip position relative to the causative pathology at the
      time of injection. Different injection sites may provide different symptomatic
      benefits. We investigated the variation in injection techniques of practitioners
      working in the UK. METHODS: A clinical scenario was devised depicting a patient
      with radiculopathy secondary to an L4/5 vertebral disc prolapse. Participants
      were questioned on their chosen management of this patient, focusing particularly
      on SNRB technique. Questionnaires were sent to spinal surgeons, pain management
      specialists and musculoskeletal radiologists. RESULTS: A total of 100 responses
      were detailed enough for inclusion. The majority (83%) of respondents reported
      they would inject local anaesthetic and steroids, 4% would inject local
      anaesthetic alone and 13% would inject a different substance. Over half (53%)
      would target the L5 nerve root, 26% the L4 nerve root, 12% the prolapsed disc
      itself and 9% two separate vertebral levels. Variation was also noted in needle
      tip location relative to the neural sheath. CONCLUSIONS: When treating lumbar
      radiculopathy, there are apparent variations in the use and positioning of SNRBs
      for a given level of disc pathology. Needle tip position may have a direct
      influence on clinical outcome following SNRBs. Caution is therefore required when
      considering the validity of previously published studies investigating SNRBs and
      different injectates.

PMID- 24112501
TI  - Scarpa's fascia and clinical signs: the role of the membranous superficial fascia
      in the eponymous clinical signs of retroperitoneal catastrophe.
AB  - INTRODUCTION: The membranous superficial fascia (MSF) was described early in the
      19th century, as was its role in the clinical sign of urethral disruption.
      Clinical signs of haemorrhage or leakage of pancreatic and biliary fluid into the
      retroperitoneum, which were described throughout the 20th century, all relied on
      circumscribed discolouration of the skin of the torso. The objective of this
      study was to relate the anatomy of the MSF to clinical signs of retroperitoneal
      catastrophe. METHODS: The MSF was dissected in the torso of seven embalmed
      cadavers to note its extent and its attachments. The attachments of the MSF were
      mapped to the areas of skin discolouration that are described in the clinical
      signs. RESULTS: The well known extent of the MSF in the inguinal region, its
      continuation into the perineum and its attachment to the fascia lata of the thigh
      were confirmed with our method of dissection. Dissection was continued
      superiorly, demonstrating continuation of the MSF over the entire torso with
      loose fibrous attachment of the MSF to the deep fascia. The MSF is firmly
      adherent to the midline of the abdomen except for the umbilicus, to a horizontal
      line below the clavicles and laterally in the abdomen to form pockets. The lines
      of firm adhesion correspond with the borders of the discoloured areas described
      in the clinical signs. CONCLUSIONS: Circumscription of discolouration seen in the
      eponymous clinical signs of retroperitoneal catastrophe is explained by
      confinement of coloured retroperitoneal fluid by the MSF and its deep
      attachments.

PMID- 24112503
TI  - Easier bone graft harvesting when performing a tibiotalocalcaneal fusion.

PMID- 24112502
TI  - Recurrent urolithiasis following parathyroidectomy for primary
      hyperparathyroidism.
AB  - INTRODUCTION: The effect of parathyroidectomy on the incidence of recurrent stone
      formation is uncertain. We aimed to compare the biochemistry and recurrence rate
      of urolithiasis in patients with primary hyperparathyroidism (pHPT) and stone
      formation (SF) and non-stone formation (NSF) with idiopathic stone formers (ISF).
      METHODS: Patients with pHPT and SF (Group 1) were identified from a prospective
      database. pHPT patients and NSF (Group 2) and ISFs (Group 3) were randomly
      selected from respective databases to form three equal groups. Preoperative and
      postoperative biochemical data were analysed and recurrent urolithiasis diagnosed
      if present on follow-up radiology. Out-of-area patients were asked about
      recurrence via telephone. RESULTS: From July 2002 to October 2011, 640 patients
      had parathyroidectomy for pHPT. Of these, 66 (10.3%) had a history of renal
      colic; one was lost to follow-up. Patient demographics were similar across all
      three groups. Three months post-parathyroidectomy, Groups 1 and 2 had
      significantly reduced serum calcium concentrations (p<0.01). Group 1 had lower
      urinary calcium excretion after parathyroidectomy (p<0.01), but estimated
      glomerular filtration rate did not change following surgery. During median follow
      up of 4.33 years (0.25-9 years) in Groups 1 and 2 and 5.08 years (0.810-8 years)
      in Group 3, one patient (1.5%) in Group 1 and 16 patients (25%) in Group 3 had
      recurrent urolithiasis (p<0.01). No Group 2 patients developed stones.
      CONCLUSION: Curative parathyroidectomy confers a low recurrence rate for
      urolithiasis, but does not prevent recurrence in all patients. Further research
      should aim to identify the risk factors for continued SF in these patients.

PMID- 24112504
TI  - Technique for cuffed central line insertion in paediatric cases.

PMID- 24112505
TI  - loop stitch technique for hamstring tendon grafts.

PMID- 24112506
TI  - A technique for avoiding notching of the anterior femur in total knee
      arthroplasty.

PMID- 24112507
TI  - Rectal sling technique to assist rectal washout during laparoscopic anterior
      resection for colorectal cancer.

PMID- 24112508
TI  - An arrangement of supports to improve access for distal interlocking in
      intramedullary tibial nailing.

PMID- 24112509
TI  - A novel way to template trochanteric hip fractures.

PMID- 24112510
TI  - A secure retraction technique for exposing the internal mammary vessels.

PMID- 24112511
TI  - The use of a 3.5mm drill sleeve to harvest bone graft.

PMID- 24112512
TI  - Nice news in the annals.

PMID- 24112514
TI  - Nuclear phosphoinositides and their impact on nuclear functions.
AB  - Polyphosphoinositides (PPIn) are important lipid molecules whose levels are de
      regulated in human diseases such as cancer, neurodegenerative disorders and
      metabolic syndromes. PPIn are synthesized and degraded by an array of kinases,
      phosphatases and lipases which are localized to various subcellular compartments
      and are subject to regulation in response to both extra- and intracellular cues.
      Changes in the activities of enzymes that metabolize PPIn lead to changes in the
      profiles of PPIn in various subcellular compartments. Understanding how
      subcellular PPIn are regulated and how they affect downstream signaling is
      critical to understanding their roles in human diseases. PPIn are present in the
      nucleus, and their levels are changed in response to various stimuli, suggesting
      that they may serve to regulate specific nuclear functions. However, the lack of
      nuclear downstream targets has hindered the definition of which pathways nuclear
      PPIn affect. Over recent years, targeted and global proteomic studies have
      identified a plethora of potential PPIn-interacting proteins involved in many
      aspects of transcription, chromatin remodelling and mRNA maturation, suggesting
      that PPIn signalling within the nucleus represents a largely unexplored novel
      layer of complexity in the regulation of nuclear functions. 

PMID- 24112515
TI  - Finding of nevirapine extended release tablet remnants in stools does not
      threaten the success of combination antiretroviral therapy.
AB  - OBJECTIVES: The finding of nevirapine extended release (XR) tablet remnants in
      stools has raised concerns about emerging HIV-1 resistance. The aim of this study
      was to evaluate the characteristics and pharmacokinetic and virological outcomes
      of affected patients from clinical trials. METHODS: HIV-1-infected individuals
      reporting tablet remnants in stools during phase III (VERxVE and TRANxITION
      studies)-clinical trials were evaluated for mean pharmacokinetic nevirapine
      concentrations in available blood trough samples and remnants from stool. Patient
      characteristics including age, race, geographical region and primary study
      endpoint outcome were investigated for risk factor association with the finding
      of tablet remnants. RESULTS: Of 800 patients receiving the nevirapine XR
      formulation, 15 reported tablet remnants in stools, an incidence rate of 1.19% in
      VERxVE and 3.05% in the TRANxITION study. The difference in event rate was highly
      significant between the XR and immediate release (IR) formulations (P < 0.001),
      but not between trials (P = 0.061). All patients (15 of 15) reporting remnants
      achieved the primary study endpoint of HIV-1 suppression (< 50 HIV-1 RNA
      copies/mL), whereas overall 81% of patients in the VERxVE trial and 94% in the
      TRANxITION trial did so. The mean nevirapine trough concentration was 3431.4
      ng/mL in patients reporting remnants. Tablet remnants retrieved from the stools
      of three subjects revealed a percentage nevirapine recovery of 22.8-42.2% of
      original drug. Subgroup analysis of gender, age, race and geographical region
      revealed no risk factor association with the finding of remnants. CONCLUSIONS:
      The finding of nevirapine tablet remnants in stools is a rare event, with an
      incidence of approximately 2%, restricted to the XR formulation. Affected
      patients responded fully to antiretroviral therapy by achieving the primary study
      endpoint and demonstrating no relevant safety risks; nevirapine pharmacokinetic
      analysis of blood and stool samples ruled out underexposure.

PMID- 24112516
TI  - Educational background of Flemish dental practitioners and their perceptions of
      their management of dental trauma.
AB  - AIM: The aim of this study was to analyze whether any correlation existed between
      Flemish dental practitioner's educational background and their perceptions of
      their knowledge regarding emergency treatment for crown fractures and their
      actual expertise. METHODS: A questionnaire was distributed among 336 dental
      practitioners at six different locations in the country and completed prior to a
      lecture on dental traumatology. The response rate was 100%. The questionnaire
      consisted of three parts: the first part enquired about personal background, the
      second part requested a self-assessment of the practitioner's dental trauma
      education and treatment experience, and the third part tested the knowledge of
      the practitioner by asking for responses to different options for emergency
      treatment for dental trauma. RESULTS: Nearly 63% of the participants had more
      than 20 years of experience. Satisfaction about adequacy in basic education in
      dental traumatology was significantly related to the years as graduation to older
      graduates being less satisfied. This observation was not related to the
      additional education taken. Most frequently, uncomplicated crown fractures (42%)
      were seen more frequently than severe injuries. Concerning knowledge, a high
      result (67%) of incorrect answers was given for the treatment for injured
      immature permanent incisors. However, a high correlation was found between good
      knowledge of treatment and young professionals who graduated <10 years ago.
      Referring dental injuries for treatment was correlated with increasing level of
      difficulty. In the permanent dentition, however, complicated crown fractures
      (CCF) in immature teeth were not referred in many (66%) cases. CONCLUSION: It was
      observed that the knowledge of Flemish dental practitioners regarding emergency
      treatment for CCF is insufficient especially for the management of immature
      incisors.

PMID- 24112517
TI  - Cell transplantation in the damaged adult brain.
AB  - Parkinson's disease (PD) is the most common movement disorder in Europe,
      affecting more than two million people between 50 and 70 years of age. The
      current therapeutic approaches are of symptomatic nature and fail to halt the
      progressive neurodegenerative course of the disease. The development of
      innovative and complementary approaches to promote cellular repair may pave the
      way for disease-modifying therapies which may lead to less suffering for the
      patients and their families and finally to more cost-effective therapies. To
      date, cell replacement trials in PD aiming at replacing lost dopamine neurons
      were mainly focused on placing the transplanted cells within the target site, the
      striatum, and not within the lesioned site, the substantia nigra (SN). This was
      based on the misconception that the adult brain constitutes a non-permissive
      barrier not allowing the outgrowth of long distance axons originating from
      transplanted embryonic neurons. A growing body of evidence is challenging this
      concept and proposing instead to place the graft within its ontogenic site. This
      has been performed in several lesional animal models for various traumatic or
      neurodegenerative pathologies of the brain. For instance, transplanted neurons
      within the lesioned motor cortex were shown to be able to send distant and
      appropriate projections to target areas including the spinal cord. Similarly, in
      an animal model of PD, mesencephalic embryonic cells transplanted within the
      lesioned SN send massive projections to the striatum and, to a lesser extent, the
      frontal cortex and the nucleus accumbens. This has lead to the proposal that
      homotopic transplantation may be an alternative in cell-based therapies as
      transplanted neurons can integrate within the host brain, send projections to
      target areas, restore the damaged circuitry, increase neurotransmitter levels and
      ameliorate behavior. We will discuss also the potential of replacing embryonic
      neuronal cells by stem cell derived neurons as the use of embryonic cells is not
      without an ethical and logistical burden; in this line many have thrived to
      derive neurons from embryonic stem cells (ESC) in order to use them for cell
      transplantation. These studies are already yielding important information for
      future approaches in the field of cell therapies in PD but also in other
      neurodegenerative disorders where cell transplantation therapy may be considered.
      While the field of cell replacement therapies has been recently called into
      question with contrasting results in transplanted PD patients, these new sets of
      findings are raising new hopes and opening new avenues in this rejuvenated field.

PMID- 24112519
TI  - Orgasmic headache treated with nimodipine.

PMID- 24112518
TI  - Serum electrolyte levels in relation to macrovascular complications in Chinese
      patients with diabetes mellitus.
AB  - BACKGROUND: The prevalence of diabetes in China is increasing rapidly. However,
      scarce data are available on serum electrolyte levels in Chinese adults with
      diabetes, especially in those with cardiovascular complications. This study
      measured serum electrolyte levels and examined their relationship with
      macrovascular complications in Chinese adults with diabetes. METHODS: The three
      gender- and age-matched groups were enrolled into this analysis, which were 1,170
      subjects with normal glucose regulation (NGR), 389 with impaired glucose
      regulation (IGR) and 343 with diabetes. Fasting plasma glucose (FPG), 2-hour post
      load plasma glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and serum
      electrolyte levels were measured. Data collection included ankle brachial index
      results. RESULTS: Serum sodium and magnesium levels in the diabetes group were
      significantly decreased compared to the NGR group (sodium: 141.0 +/- 2.4 vs.
      142.1 +/- 2.0 mmol/l; magnesium: 0.88 +/- 0.08 vs. 0.91 +/- 0.07 mmol/l, all P <
      0.01), while the serum calcium level was significantly increased (2.36 +/- 0.11
      vs. 2.33 +/- 0.09 mmol/l, P < 0.01). Multiple linear regression showed that serum
      sodium and magnesium levels in the diabetes group were negatively correlated with
      FPG, 2hPG and HbA1c (sodium: Std beta = -0.35, -0.19, -0.25; magnesium: Std beta
      = -0.29, -0.17, -0.34, all P < 0.01), while the serum calcium level was
      positively correlated with HbA1c (Std beta = 0.17, P < 0.05). In diabetic
      subjects, serum sodium, magnesium and potassium levels were decreased in the
      subjects with the elevation of estimated glomerular filtration rates (P < 0.05).
      ANCOVA analysis suggested that serum magnesium level in subjects with diabetic
      macrovascular complications was significantly decreased compared with diabetic
      subjects without macrovascular complications after the effect of some possible
      confounding being removed (P < 0.05). CONCLUSIONS: Serum sodium and magnesium
      levels were decreased in Chinese subjects with diabetes, while the observed
      increase in calcium level correlated with increasing glucose level. Diabetic
      patients with macrovascular complications had lower serum magnesium level than
      those with no macrovascular complications.

PMID- 24112520
TI  - Ontogenetic allometry of the Beagle.
AB  - BACKGROUND: Mammalian juveniles undergo dramatic changes in body conformation
      during development. As one of the most common companion animals, the time line
      and trajectory of a dog's development and its body's re-proportioning is of
      particular scientific interest. Several ontogenetic studies have investigated the
      skeletal development in dogs, but none has paid heed to the scapula as a critical
      part of the mammalian forelimb. Its functional integration into the forelimb
      changed the correspondence between fore- and hindlimb segments and previous
      ontogenetic studies observed more similar growth patterns for functionally than
      serially homologous elements. In this study, the ontogenetic development of six
      Beagle siblings was monitored between 9 and 51 weeks of age to investigate their
      skeletal allometry and compare this with data from other lines, breeds and
      species. RESULTS: Body mass increased exponentially with time; log linear
      increase was observed up to the age of 15 weeks. Compared with body mass, withers
      and pelvic height as well as the lengths of the trunk, scapula, brachium and
      antebrachium, femur and crus exhibited positive allometry. Trunk circumference
      and pes showed negative allometry in all, pelvis and manus in most dogs. Thus,
      the typical mammalian intralimb re-proportioning with the proximal limb elements
      exhibiting positive allometry and the very distal ones showing negative allometry
      was observed. Relative lengths of the antebrachium, femur and crus increased,
      while those of the distal elements decreased. CONCLUSIONS: Beagles are fully
      grown regarding body height but not body mass at about one year of age.
      Particular attention should be paid to feeding and physical exertion during the
      first 15 weeks when they grow more intensively. Compared with its siblings, a
      puppy's size at 9 weeks is a good indicator for its final size. Among siblings,
      growth duration may vary substantially and appears not to be related to the adult
      size. Within breeds, a longer time to physically mature is hypothesized for
      larger-bodied breeding lines. Similar to other mammals, the Beagle displayed
      nearly optimal intralimb proportions throughout development. Neither the
      forelimbs nor the hindlimbs conformed with the previously observed proximo-distal
      order of the limb segment's growth gradients. Potential factors responsible for
      variations in the ontogenetic allometry of mammals need further evaluation.

PMID- 24112521
TI  - The fate of PrP GPI-anchor signal peptide is modulated by P238S pathogenic
      mutation.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are localized to the plasma
      membrane via a C-terminally linked GPI anchor. The GPI anchor is added
      concomitantly to the cleavage of the carboxy-terminal GPI-anchor signal sequence,
      thereby causing the release of a C-terminal hydrophobic peptide, whose fate has
      not yet been investigated. Here we followed the fate of the GPI-attachment signal
      of the prion protein (PrP), a protein implicated in various types of
      transmissible neurodegenerative spongiform encephalopathies (TSE). The PrP GPI
      anchor signal sequence shows a remarkable and unusual degree of conservation
      across the species and contains two point mutations (M232R/T and P238S) that are
      responsible for genetic forms of prion disorders. We show that the PrP GPI-anchor
      signal peptide (SP), but not the one from an unrelated GPI-anchored protein
      (folate receptor), undergoes degradation via the proteasome. Moreover, the P238S
      point mutation partially protects the PrP GPI-anchor SP from degradation. Our
      data provide the first attempt to address the fate of a GPI-anchor SP and
      identify a role for the P238S mutation, suggesting the possibility that the PrP
      GPI-anchor SP could play a role in neurodegenerative prion diseases. 

PMID- 24112522
TI  - Editorial Comment to Soft coagulation in partial nephrectomy without renorrhaphy:
      feasibility of a new technique and early outcomes.

PMID- 24112523
TI  - Gray matter differences contribute to variation in cognitive performance in
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: A substantial proportion of patients with Parkinson's
      disease (PD) suffer from cognitive deficits, although there is a large
      variability in the severity of these impairments. Whilst the cognitive deficits
      are often attributed to monoaminergic changes, there is evidence that alterations
      in structural brain volume also play a role. The aim of our study was to gain
      more insight into the variability of cognitive performance amongst PD patients by
      examining the relation between regional gray matter (GM) volume and cognitive
      performance. METHODS: Linear regression analyses were performed between task
      performance and GM volume for six neuropsychological tasks within a group of 93
      PD patients; they were additionally compared at a group level with matched
      healthy controls, using voxel-based morphometry. RESULTS: Our most important
      findings were positive correlations between GM volume and cognitive performance
      for (i) parahippocampal gyrus and verbal memory, (ii) medial temporal lobe and
      putamen and visuospatial memory, and (iii) middle temporal gyrus and frontal lobe
      and verbal fluency. In addition, decreased GM volume was found in the frontal,
      parietal and temporal cortices of PD patients compared with matched healthy
      controls. CONCLUSIONS: It is argued that the large variability in cognitive
      function across PD patients is partly mediated by GM volume differences in the
      implicated areas. Volume differences in these brain regions do not discriminate
      between patients and controls but explain cognitive variation within the patient
      population.

PMID- 24112524
TI  - Comparison of SLA(r) or SLActive(r) implants placed in the maxillary sinus with
      or without synthetic bone graft materials--an animal study in sheep.
AB  - AIMS: To assess the influence of an activated implant surface and a synthetic
      graft material in the maxillary sinus in combination with sinus floor elevation
      on bone-to-implant contact (BIC) as compared to implants with conventional
      surfaces. MATERIAL AND METHODS: In 16 sheep, sinus bone augmentation was
      performed using a synthetic bone graft material according to the methods
      described by Haas et al (Clinical Oral Implants Research, 9, 1998, 107; Clinical
      Oral Implants Research, 13, 2002, 396). Another 16 sheep received a sinus floor
      elevation procedure without graft material. Using a paired design, in one sinus
      of each animal, a conventional implant was placed, whereas an implant with
      activated surface was placed in the other. Eight animals of each group were
      sacrificed at 12 weeks and the others at 26 weeks after surgery. Histological
      analysis was performed to analyse BIC. Results were statistically compared at a
      significance level of P < 0.05. RESULTS: After 12 weeks, the BIC for conventional
      and activated implants with or without graft showed comparable results, with mean
      values of 14.8%, 16.5%, 21.5% and 20.1% (P > 0.05). For ungrafted sinuses after
      26 weeks, no increase in BIC was recorded (12.1% conventional surface, 15.8%
      activated surface; P > 0.05). In grafted sinuses after 26 weeks, mean values
      increased to 28.7% for conventional and 34.1% for activated implants (P = 0.014;
      P = 0.015). However, only BIC of the latter was statistically significantly
      higher compared with ungrafted sinuses (P = 0.038). CONCLUSION: After 12 weeks of
      healing, neither grafting nor implant type seemed to influence BIC. Use of an
      activated implant surface did not increase BIC when compared with a conventional
      implant. The synthetic graft seemed to improve BIC values after 26 weeks.

PMID- 24112525
TI  - Endometriosis: the elusive gray area between evidence-based and evidence-biased
      medicine.

PMID- 24112526
TI  - Society for Assisted Reproductive Technology/Centers for Disease Control and
      Prevention in vitro fertilization registry 2.0.

PMID- 24112527
TI  - An overview of the current status of clinical trials on endometriosis: issues and
      concerns.
AB  - OBJECTIVE: To examine and compare differences, if any, between industry- and
      nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect
      of prior published positive preclinical results, or lack thereof, on trial
      status. DESIGN: Cross-sectional study of clinical trials on endometriosis that
      evaluate drugs/biologicals registered at ClinicalTrials.gov as of July 3, 2013.
      SETTING: University-affiliated hospital. PATIENT(S): None. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Trial status, size, phase, and duration; use of
      comparator groups; drug classes, number of arms, targeting conditions; and
      presence or absence of prior positive preclinical results before the launch of
      the trial. RESULT(S): Eighty trials were identified. The trials sponsored by
      industry and non-industry have distinct features, differing in trial status,
      phase, comparator, drug classes, number of arms, trial size, and duration. The
      phase II/III trials are predominantly industry supported, but these trials
      frequently use placebo as the comparator. Trials launched without prior published
      preclinical results do not seem to fare well, although the presence of such
      studies is no guarantee for success. CONCLUSION(S): Questions as to whether the
      drug on trial is truly superior to the best available drug or of its cost-benefit
      profile are overlooked in most cases. There seems to be a deluge of "me-too"
      drugs with equivocal superiority over existing drugs and cost-benefit profiles.
      Because clinical trials are time-consuming, no blockbuster drug for endometriosis
      seems to be on the horizon yet.

PMID- 24112528
TI  - Addition of nitrous oxide to the carbon dioxide pneumoperitoneum strongly
      decreases adhesion formation and the dose-dependent adhesiogenic effect of blood
      in a laparoscopic mouse model.
AB  - OBJECTIVE: To evaluate the effect of addition of nitrous oxide (N2O) to the
      carbon dioxide (CO2) pneumoperitoneum (PP) and the effect of blood, plasma, or
      red blood cells (RBCs) on postoperative adhesions in a laparoscopic mouse model.
      DESIGN: Prospective randomized controlled trial. SETTING: University laboratory
      research center. ANIMAL(S): BALB/c female mice. INTERVENTION(S): The effect of
      adding to the 60-minute CO2 PP 5%, 10%, 25%, 50%, or 100% N2O on adhesion
      formation was evaluated. Subsequently the effect of adding 1 mL blood, or RBCs,
      or plasma and the effect of adding different concentrations of blood were
      studied. Finally, the effect of adding 10% N2O, 4% O2, or both to the CO2 was
      evaluated in a control group and after addition of blood. MAIN OUTCOME
      MEASURE(S): Postoperative adhesions after 7 days. RESULT(S): N2O strongly reduces
      adhesion formation with a full effect at a concentration of 5% or 10%. Adhesions
      increase linearly with 0.125 mL to 1 mL blood. In both the control group and
      after adding blood, 10% N2O is the most effective factor in prevention of
      adhesions. CONCLUSION(S): N2O, from concentrations of 5% upward, strongly
      prevents adhesion formation. Blood, mainly the plasma, increases adhesion
      formation. These data extend the concept of the role of acute inflammation and
      support the importance of good surgical practice with little bleeding and
      peritoneal cavity conditioning in adhesion prevention.

PMID- 24112529
TI  - An assessment of current clinical attitudes toward letrozole use in reproductive
      endocrinology practices.
AB  - OBJECTIVE: To assess the clinical use and practice attitudes among Society for
      Assisted Reproductive Technology (SART) members regarding the use of letrozole
      for ovulation induction and infertility treatment. DESIGN: The SART clinic
      physicians were mailed a cover letter and consent form, a two-page survey, and
      return envelope. The surveys were returned and analyzed using descriptive
      statistics. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): A 13
      question survey. MAIN OUTCOME MEASURE(S): Reproductive endocrinology and
      infertility physicians use patterns and attitudes regarding letrozole. RESULT(S):
      A total of 77.9% of physician prescribe letrozole. Of those who do not, 32.4%
      cited concern about the US Food and Drug Administration warning, 35.1% cited
      satisfaction with current medications, 25.7% cited both reasons, and 6.8% cited
      no experience with letrozole. Physicians (11.5%) were unaware of the US Food and
      Drug Administration warning. Physicians (99.7%) were aware that ovulation
      induction is an off-label use of letrozole. The most common use was for ovulation
      induction in patients with polycystic ovary syndrome (PCOS). Physicians (14.9%)
      prescribe letrozole as first-line ovulation therapy prior to clomid, 47.9% use
      for clomid failures, and 25.7% reported use in both situations. CONCLUSION(S):
      Most physicians surveyed use letrozole for ovulation induction despite the
      current US Food and Drug Administration warning. Even when accounting for
      nonrespondents, more than 25% of physicians indicated success with letrozole use.
      Questions regarding doses and clinical concerns about letrozole revealed no
      standardized manner of letrozole administration despite wide interest, therefore
      additional research is warranted.

PMID- 24112530
TI  - WITHDRAWN: What makes them split? Identifying risk factors that lead to
      monozygotic twins after in vitro fertilization.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24112531
TI  - Experience with ISO quality control in assisted reproductive technology.
AB  - Assisted reproductive technology (ART) programs are complex organizations
      requiring the integration of multiple disciplines. ISO 9001:2008 is a quality
      management system that is readily adaptable to an ART program. The value that ISO
      brings to the entire organization includes control of documents, clear
      delineation of responsibilities of staff members, documentation of the numerous
      processes and procedures, improvement in tracking and reducing errors, and
      overall better control of systems. A quality ART program sets quality objectives
      and monitors their progress. ISO provides a sense of transparency within the
      organization and clearer understanding of how service is provided to patients.
      Most importantly, ISO provides the framework to allow for continual improvement. 

PMID- 24112532
TI  - Cigarette smoking is associated with abnormal histone-to-protamine transition in
      human sperm.
AB  - OBJECTIVE: To investigate the association between smoking, semen quality, and the
      histone-to-protamine transition ratio in mature sperm. DESIGN: Biochemical and
      molecular analysis in human samples and a cell line. SETTING: Andrology
      laboratory in a university-affiliated hospital. PATIENT(S): Semen samples from
      147 heavy smokers and 175 nonsmokers receiving infertility treatment.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Basic semen parameters, histone
      to-protamine ratios, and number of sperm cells with abnormal histone transition
      were calculated. The relative messenger RNA (mRNA) expression levels of protamine
      1 and protamine 2 were assayed in human sperm and in TM3 cells exposed to
      cigarette smoke condensate. T tests, Spearman tests, and nonparametric Mann
      Whitney U tests were used to detect significant differences. RESULT(S):
      Normozoospermic smokers had significantly higher abnormalities than their
      nonsmoking counterparts. Sperm histone replacement abnormalities were found to be
      closely correlated with sperm motility, viability, concentration, counts, and
      cotinine levels. The ratios of protamine 1 to protamine 2 mRNA expression
      significantly increased in heavy smokers and in TM3 cells treated with cigarette
      smoke condensate. CONCLUSION(S): Smoking is strongly associated with
      abnormalities in histone-to-protamine transition and with alteration of protamine
      mRNA expression in human sperm.

PMID- 24112533
TI  - Plasma D-dimer concentrations during experimental EHV-1 infection of horses.
AB  - BACKGROUND: Central nervous system blood vessel thrombosis is a part of the
      pathogenesis of equid herpesvirus-associated myeloencephalopathy (EHM). D-dimers
      (DD) are stable breakdown products of cross-linked fibrin, and increased DD
      plasma concentrations could reflect the degree of systemic coagulation during EHV
      1 infection. HYPOTHESIS: We hypothesized that blood DD concentrations will be
      increased during periods of EHV-1 fever and viremia, reflecting an activated
      coagulation cascade with fibrinolysis. ANIMALS: Twenty-eight equids were infected
      with EHV-1 in 3 experimental infection studies. Three (uninfected) horses were
      included in a separate study to evaluate methodology for DD concentration
      measurements. METHODS: Clinical data and quantitative viremia were evaluated, and
      DD concentrations were measured in blood samples on the day before the infection
      and during days 1-12 postchallenge. Uninfected horses were sampled every 3 hours
      for 48 hours. Logistic and linear regression was used to investigate the
      potential association between the fever and viremia with the presence or absence
      of DD concentrations in peripheral blood. RESULTS: DD concentrations were
      increased for 1-8 days in the majority of infected animals. Both viremia (odds
      ratio [OR] 6.3; 95% confidence interval [CI] 3.4-11.8; P = .0013) and fever (OR
      4.9; CI 2.3-10.1; P = .001) were strongly associated with the likelihood of
      detecting DD in peripheral blood. CONCLUSIONS AND CLINICAL IMPORTANCE: EHV-1
      viremia is associated with increases in DD concentration in horses and ponies.
      This indicates that EHV-1 viremia can lead to an activation of coagulation and
      fibrinolysis.

PMID- 24112534
TI  - Wide complex tachycardia in the presence of class I antiarrhythmic agents: a
      diagnostic challenge.
AB  - We present two patients with paroxysmal atrial fibrillation on class 1C
      antiarrhythmic drugs without concomitant atrioventricular (AV) nodal blocking
      agents who developed atrial flutter with 1:1 AV conduction. Their
      electrocardiogram revealed wide complex tachycardia with rates >200/minute.
      Atrial flutter with 1:1 conduction in the presence of class IC antiarrhythmic
      drugs may present a diagnostic challenge. These cases illustrate the importance
      of coadministering an AV nodal blocking agent with class IC antiarrhythmic agents
      in patients with atrial fibrillation. The differential diagnosis of wide complex
      tachycardia in patients taking class IC agents should include atrial flutter with
      1:1 AV conduction.

PMID- 24112535
TI  - Validity of the Morse Fall Scale implemented in an electronic medical record
      system.
AB  - AIMS AND OBJECTIVES: To examine the validity of the Morse Fall Scale by analysing
      the electronic medical records on fall risk during different phases of
      hospitalisation. BACKGROUND: Regular monitoring on fall risk with a reliable and
      valid assessment tool is a key element in the fall prevention. In Korea, the
      Morse Fall Scale is currently being used in numerous medical institutions, yet it
      has not been comprehensively evaluated whether it is suitable and valid. DESIGN:
      The study design was a retrospective case-control study. METHODS: The
      participants included 151 fallers and 694 nonfallers. Data were extracted from a
      university hospital implementing Morse Fall Scale in the electronic medical
      records between October 2010 and June 2011. The nonfallers were selected by the
      stratified random sampling method among the patients who were in the hospital
      during the same period as the fallers. The Morse Fall Scale scores during three
      different time periods of hospital stay were used for analysis: the initial
      assessment score upon admission, the last and the maximum scores recorded from
      admission to the fall or discharge. RESULTS: With the maximum Morse Fall Scale
      score and the best cut-off point of 51, validity indicators showed the highest
      performance: 0.72 for sensitivity, 0.91 for specificity, 0.63 for positive
      predictive value, 0.94 for negative predictive value, 0.63 for Youden Index and
      0.77 for the area under the receiver operating characteristic curve. CONCLUSION:
      The Morse Fall Scale showed relatively high predictive performance for the Korean
      population. RELEVANCE TO CLINICAL PRACTICE: The study results recommend practice
      change in fall prevention. As the validity was highest when the patient was first
      classified into the high-risk group based on the Morse Fall Scale cut-off score
      51, patients classified as high risk should be placed under special nursing
      interventions until the day of their discharge, regardless of change in the
      patient state.

PMID- 24112536
TI  - Mental health self-assessment in patients with moderate to severe psoriasis: an
      observational, multicenter study of 1164 patients in Spain (the VACAP Study).
AB  - BACKGROUND: Poor self-assessed mental health appears to be related to the
      severity of psoriasis. OBJECTIVE: To evaluate the impact of psoriasis severity on
      mood and anxiety disorders. METHODS: A prospective, observational, multicenter
      study was conducted by 123 dermatologists in Spain. Patients (n=164; mean [SD]
      age, 45.11 [13.92] years; 60.8% males) with moderate to severe psoriasis were
      evaluated at baseline and 4 months later. Psoriasis severity was measured using
      the Psoriasis Area and Severity Index (PASI), with a score range of 0 (mild) to
      72 (severe); body surface area involvement (BSA); and physician global assessment
      (PGA) scores, with a range of 1 (mild) to 7 (severe). Mental health was assessed
      using the Hospital Anxiety and Depression Scale (HADS), with a total possible
      score of 0-42 (higher scores representing worse mental health). Mean first and
      second visit scores were compared. RESULTS: Mean (SD) scores improved between the
      first and second visit as follows: 13.24 (9.50) to 5.07 (6.03) for PASI, 12.52
      (7.92) to 10.78 (7.32) for overall HADS, 7.83 (4.55) to 6.85 (4.21) for the HADS
      anxiety subscale, and 4.72 (4.12) to 3.95 (3.76) for the HADS depression subscale
      (P<.001 in all cases). Multivariate analyses showed that the main factors related
      to anxiety were psoriasis severity, sex, and completion of graduate studies. The
      independent variables included in the model for depression were psoriasis
      severity, sex, and psoriasis located on the head. CONCLUSIONS: Reductions in
      disease severity improve self-assessed mood and anxiety disorders in patients
      with moderate to severe psoriasis.

PMID- 24112539
TI  - MicroRNA-21 promotes hepatocellular carcinoma HepG2 cell proliferation through
      repression of mitogen-activated protein kinase-kinase 3.
AB  - BACKGROUND: microRNA 21 (miR-21) has been demonstrated to be significantly
      elevated in many types of cancers, including the hepatocellular carcinoma (HCC).
      In the present study, we investigated the role of miR-21 in HCC by identifying
      its novel targets, as well as its underlying molecular mechanism. METHODS: The
      expression of mitogen-activated protein kinase-kinase 3 (MAP2K3) in human HCC
      tumor tissues and adjacent non-tumor tissues was determined by
      immunohistochemistry staining (IHC) analysis. The 3'-untranslated region (3'-UTR)
      of MAP2K3 combined with miR-21 was experimentally verified by a miRNA luciferase
      reporter approach. Moreover, the role of miR-21 in regulating HCC cell
      proliferation was analyzed by an MTT assay infected with miR-21mimics/sponge
      inhibitor Adenoviral viral vectors. RESULTS: By immunohistochemistry staining
      analysis, we found that mitogen-activated protein kinase-kinase 3 (MAP2K3) was
      strikingly repressed in the human HCC tumor tissues, in comparison with the
      adjacent non-tumor tissues in clinical settings. More importantly, the repression
      of MAP2K3 was inversely correlated with the expression of miR-21 in HCC. Further
      study demonstrated that the MAP2K3 was a novel direct target of miR-21, which was
      experimentally validated by a miRNA luciferase reporter approach. In HepG2 cells,
      inhibition of miR-21 expression with an adenoviral miR-21 sponge vector
      profoundly suppressed cell proliferation by up-regulating MAP2K3 expression at
      both mRNA and protein levels. CONCLUSIONS: These results provide a clinical
      evidence that MAP2K3 may be a tumor repressor gene, and it is a direct target of
      miR-21 in HCC, indicating an underlying mechanism by which miR-21 is able to
      directly target MAP2K3 and inhibit its expression during the carcinogenesis of
      HCC, at both transcriptional and post-translational levels. This study also
      suggests that targeting miR-21-MAP2K3 pathway may be a promising strategy in the
      prevention and treatment of HCC.

PMID- 24112540
TI  - Clinical predictive value of manual muscle strength testing during critical
      illness: an observational cohort study.
AB  - INTRODUCTION: Impaired skeletal muscle function has important clinical outcome
      implications for survivors of critical illness. Previous studies employing
      volitional manual muscle testing for diagnosing intensive care unit-acquired
      weakness (ICU-AW) during the early stages of critical illness have only provided
      limited data on outcome. This study aimed to determine inter-observer agreement
      and clinical predictive value of the Medical Research Council sum score (MRC-SS)
      test in critically ill patients. METHODS: Study 1: Inter-observer agreement for
      ICU-AW between two clinicians in critically ill patients within ICU (n = 20) was
      compared with simulated presentations (n = 20). Study 2: MRC-SS at awakening in
      an unselected sequential ICU cohort was used to determine the clinical predictive
      value (n = 94) for outcomes of ICU and hospital mortality and length of stay.
      RESULTS: Although the intra-class correlation coefficient (ICC) for MRC-SS in the
      ICU was 0.94 (95% CI 0.85-0.98), kappa statistic for diagnosis of ICU-AW (MRC-SS
      <48/60) was only 0.60 (95% CI 0.25-0.95). Agreement for simulated weakness
      presentations was almost complete (ICC 1.0 (95% CI 0.99-1.0), with a kappa
      statistic of 1.0 (95% CI 1.0-1.0)). There was no association observed between
      ability to perform the MRC-SS and clinical outcome and no association between ICU
      AW and mortality. Although ICU-AW demonstrated limited positive predictive value
      for ICU (54.2%; 95% CI 39.2-68.6) and hospital (66.7%; 95% CI 51.6-79.6) length
      of stay, the negative predictive value for ICU length of stay was clinically
      acceptable (88.2%; 95% CI 63.6-98.5). CONCLUSIONS: These data highlight the
      limited clinical applicability of volitional muscle strength testing in
      critically ill patients. Alternative non-volitional strategies are required for
      assessment and monitoring of muscle function in the early stages of critical
      illness.

PMID- 24112541
TI  - JadR*-mediated feed-forward regulation of cofactor supply in jadomycin
      biosynthesis.
AB  - Jadomycin production is under complex regulation in Streptomyces venezuelae.
      Here, another cluster-situated regulator, JadR*, was shown to negatively regulate
      jadomycin biosynthesis by binding to four upstream regions of jadY, jadR1, jadI
      and jadE in jad gene cluster respectively. The transcriptional levels of four
      target genes of JadR* increased significantly in DeltajadR*, confirming that
      these genes were directly repressed by JadR*. Jadomycin B (JdB) and its
      biosynthetic intermediates 2,3-dehydro-UWM6 (DHU), dehydrorabelomycin (DHR) and
      jadomycin A (JdA) modulated the DNA-binding activities of JadR* on the jadY
      promoter, with DHR giving the strongest dissociation effects. Direct interactions
      between JadR* and these ligands were further demonstrated by surface plasmon
      resonance, which showed that DHR has the highest affinity for JadR*. However,
      only DHU and DHR could induce the expression of jadY and jadR* in vivo. JadY is
      the FMN/FAD reductase supplying cofactors FMNH2/FADH2 for JadG, an oxygenase,
      that catalyses the conversion of DHR to JdA. Therefore, our results revealed that
      JadR* and early pathway intermediates, particularly DHR, regulate cofactor supply
      by a convincing case of a feed-forward mechanism. Such delicate regulation of
      expression of jadY could ensure a timely supply of cofactors FMNH2/FADH2 for
      jadomycin biosynthesis, and avoid unnecessary consumption of NAD(P)H.

PMID- 24112537
TI  - Pyrosequencing-based profiling of archaeal and bacterial 16S rRNA genes
      identifies a novel archaeon associated with black band disease in corals.
AB  - Black band disease (BBD) is a microbial consortium that creates anoxic, sulfide
      rich microenvironments and kills underlying coral tissues as it rapidly migrates
      across colonies. Although bacterial communities associated with BBD have been
      studied extensively, the presence and roles of archaea are unexplored. Using
      amplicon-pyrosequencing of 16S ribosomal RNA genes, we investigated the community
      structure of both archaea and bacteria within microbial lesions of BBD and the
      less-virulent precursor stage, 'cyanobacterial patches' (CP), affecting the coral
      Montipora hispida. We detected characteristic shifts in microbial communities
      during the development of BBD from CP, reflecting microenvironmental changes
      within lesions. Archaeal profiles in CP suggested a diverse assemblage affiliated
      with the Thaumarchaeota and Euryarchaeota, similar to communities described for
      oxic marine environments. In contrast, a novel ribotype, distantly affiliated to
      the Euryarchaeota, dominated up to 94% of archaeal sequences retrieved from BBD.
      The physiological characteristics of this dominant archaeal ribotype are unknown
      because of the novelty of its 16S ribosomal RNA gene sequences; however, their
      prominent associations with BBD lesions suggest the ability to thrive in the
      organic- and sulfide-rich anoxic microenvironment characteristic of BBD lesions.
      Discovery of this novel archaeal ribotype provides new insights into the
      microbial ecology and aetiology of BBD. 

PMID- 24112542
TI  - Iron sulfate inhibits Limulus activity by induction of structural and qualitative
      changes in lipid A.
AB  - AIMS: The bacterial endotoxins test (BET) is a sensitive assay for measuring
      endotoxin levels in solution and uses the limulus amebocyte lysate (LAL)
      coagulation reaction. We sought to identify the mechanisms through which certain
      substances interfere with the interaction between LAL and bacterial
      lipopolysaccharide (LPS). METHODS AND RESULTS: Endotoxin lipid A was inactivated
      by the addition of iron sulfate, which acted on endotoxin directly and strongly
      inhibited LAL coagulation activity. Size-exclusion, anion-exchange and reverse
      phase liquid chromatography/mass spectrometry were used to examine changes in
      inactivated lipid A in terms of complex formation, negative charge status,
      hydrophobic interaction and structure. Furthermore, we verified the involvement
      of the lipid A phosphoryl group in the interference of iron sulfate with lipid A
      factor C binding activity. Iron sulfate-inactivated lipid A was cleaved at its
      glycosidic bond, resulting in loss of hydrophobic interactions and disruption of
      lipid A complexes without alteration of negative charge status and lipid A-factor
      C interaction. CONCLUSIONS: Lipid A cleavage was a direct result of interfering
      factors, including iron sulfate, which acted on endotoxin directly to disrupt
      lipid A complexes rather than interfering with LAL coagulation. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Our data provide new insights into the mechanisms of lipid A
      activity.

PMID- 24112538
TI  - Barcoding the Collembola of Churchill: a molecular taxonomic reassessment of
      species diversity in a sub-Arctic area.
AB  - Although their functional importance in ecosystems is increasingly recognized,
      soil-dwelling micro-arthropods are usually poorly known in comparison with their
      above-ground counterparts. Collembola constitute a significant and species-rich
      component of the soil biodiversity, but it remains a woefully understudied group
      because of the taxonomic impediment. The ever-increasing use of molecular
      taxonomic tools, such as DNA barcoding, provides a possible solution. Here, we
      test the use of this approach through a diversity survey of Collembola from the
      vicinity of Churchill, Manitoba, Canada, and compare the results with previous
      surveys in the same area and in other sub-Arctic regions. The systematic
      barcoding campaign at Churchill revealed a diverse collembolan fauna consisting
      of 97 species-level MOTUs in six types of habitats. If all these MOTUs are
      confirmed as species, this richness would be far higher than prior records for
      Arctic Canada and could lead to reconsider the actual diversity of the group in
      Arctic environments. 

PMID- 24112543
TI  - Diesel exhaust particle exposure increases severity of allergic asthma in young
      mice.
AB  - BACKGROUND: Epidemiologic studies have reported an association between diesel
      exhaust particle (DEP) exposure, allergic sensitization, and childhood wheezing,
      although the mechanisms remain unclear. While DEP is known to augment allergic
      responses in adult animal models, its effects on sensitization and asthma
      severity in young animals is unknown. OBJECTIVE: To examine the impact of
      different doses of DEP and allergen co-exposure on allergic sensitization and
      asthma characteristics in young mice, and whether Th17 as well as Th2 responses
      are induced. METHODS: Lungs of 3-week-old wild-type Balb/c mice were exposed by
      pharyngeal aspiration nine times over 3 weeks to DEP at 1.2 or 6.0 mg/kg body
      weight, house dust mite (HDM) at 0.8, 1.2 or 6.0 mg/kg of DEP in combination with
      HDM, or the same volume (50 MUL) of 0.9% sterile saline. RESULTS: In young mice,
      exposure to 1.2 mg/kg of DEP caused no detectable lung inflammation, but 6.0
      mg/kg of DEP induced neutrophilic influx. Compared to HDM or DEP alone, mice
      exposed to either dose of DEP together with HDM demonstrated increased allergen
      specific IgE, lung inflammation, airway hyperreactivity, goblet cell metaplasia,
      Th2/Th17 cytokines, dendritic cells, activated T cells, effector T cells, and IL
      17(pos) and IL-13(pos) /IL-17A(pos) T effector cells. CONCLUSIONS AND CLINICAL
      RELEVANCE: In young mice, co-exposure to DEP and HDM together exacerbated
      allergic sensitization and induced key characteristics of more severe asthma,
      including IL-17A, IL-17(pos) and IL-13(pos) /IL-17A(pos) T effector cells. While
      exposure to 1.2 mg/kg DEP alone caused no detectable changes, it did exacerbate
      allergic sensitization and asthma characteristics to a similar degree as a five
      fold higher dose of DEP. This study demonstrates that exposure to DEP, even at a
      dose that alone causes no inflammation, exacerbates allergic asthma in young
      animals and suggests the importance of preventive measures to reduce the exposure
      of children to traffic related air pollution.

PMID- 24112544
TI  - An easy access to retrieve dental implants displaced into the maxillary sinus:
      the bony window technique.
AB  - AIM OF THE STUDY: To present the authors' experience concerning the removal of
      dental implants displaced in the maxillary sinus via an intraoral approach
      consisting of the creation of a bony window pedicled to the maxillary sinus
      membrane. MATERIALS AND METHODS: Thirty-six systemically healthy patients,
      presenting with oral implants displaced into the maxillary sinus, but with no
      signs of acute or chronic sinusitis, were consecutively treated between 2002 and
      2012 via an intraoral approach with the bony window technique. RESULTS: Removal
      of oral implants from the maxillary sinus was achieved in all patients, and
      postoperative recovery was uneventful in all of them. Computed tomographies
      performed after surgery showed no signs of residual sinus infection in all
      patients and a complete ossification of the bony window margins. Twelve of the 36
      treated patients were treated with a sinus grafting procedure 12-18 months after
      in the same areas previously treated with the bone lid technique. Seventeen
      implants were placed in the grafted areas 6-9 months later and, after a further
      waiting period needed for osseointegration, the treated patients were
      rehabilitated with implant-supported prostheses. The survival rate of implants
      was 100%, and no complications related to the sinuses and implants were recorded.
      CONCLUSION: Results from this study seem to demonstrate that the bony window
      technique is a safe and easy way to remove oral implants from the maxillary sinus
      under local anesthesia. The surgical access is hardly visible 6-12 months after
      surgery, and maxillary sinuses appeared free from residual pathology in all
      treated patients. Finally, this procedure allows a second-stage sinus grafting
      procedure via a lateral approach as in a previously untreated maxillary sinus,
      thus allowing an implant-supported prosthetic restoration.

PMID- 24112545
TI  - Whole brain helical Tomotherapy with integrated boost for brain metastases in
      patients with malignant melanoma-a randomized trial.
AB  - BACKGROUND: Patients with malignant melanoma may develop brain metastases during
      the course of the disease, requiring radiotherapeutic treatment. In patients with
      1-3 brain metastases, radiosurgery has been established as a treatment option
      besides surgery. For patients with 4 or more brain metastases, whole brain
      radiotherapy is considered the standard treatment. In certain patients with brain
      metastases, radiation treatment using whole brain helical Tomotherapy with
      integrated boost and hippocampal-sparing may improve prognosis of these patients.
      METHODS/DESIGN: The present prospective, randomized two-armed trial aims to
      exploratory investigate the treatment response to conventional whole brain
      radiotherapy applying 30 Gy in 10 fractions versus whole brain helical
      Tomotherapy applying 30 Gy in 10 fractions with an integrated boost of 50 Gy to
      the brain metastases as well as hippocampal-sparing in patients with brain
      metastases from malignant melanoma. The main inclusion criteria include magnetic
      resonance imaging confirmed brain metastases from a histopathologically confirmed
      malignant melanoma in patients with a minimum age of 18 years. The main exclusion
      criteria include a previous radiotherapy of the brain and not having recovered
      from acute high-grade toxicities of prior therapies. The primary endpoint is
      treatment-related toxicity. Secondary endpoints include imaging response, local
      and loco-regional progression-free survival, overall survival and quality of
      life. TRIAL REGISTRATION: http://www.drks.de Trial ID: DRKS00005127.

PMID- 24112546
TI  - Lower urinary tract symptoms in female patients with pelvic organ prolapse:
      efficacy of pelvic floor reconstruction.
AB  - OBJECTIVE: To evaluate the impact of pelvic floor reconstruction on lower urinary
      tract symptoms in patients with pelvic organ prolapse. METHODS: We carried out a
      prospective study at a single institution. A total of 223 female patients who
      underwent tension-free vaginal mesh surgery for pelvic organ prolapse between
      January 2006 and February 2010 were enrolled and prospectively evaluated. A total
      of 171 cases with concurrent stress urinary incontinence (76% of all cases)
      underwent concomitant transobturator tape sling. For evaluation of lower urinary
      tract symptoms, parameters included International Prostate Symptom Score, its
      quality of life score, International Consultation on Incontinence Questionnaires
      Short Form, overactive bladder questionnaire, maximal flow rate and postvoid
      residual. These parameters were evaluated at baseline, and at 3, 6 and 12 months
      after the surgery. RESULTS: The severity of International Prostate Symptom Score
      total scores significantly correlated with preoperative pelvic organ prolapse
      quantification stages, overactive bladder questionnaire total scores and
      International Consultation on Incontinence Questionnaires Short Form scores. A
      total of 37% of stage 4 showed >=20 International Prostate Symptom Score (severe
      cases). Postvoid residual significantly increased in stage 4 compared with stage
      2. Tension-free vaginal mesh improved International Prostate Symptom Score,
      overactive bladder questionnaire and International Consultation on Incontinence
      Questionnaires Short Form significantly, and also achieved grade 0 pelvic organ
      prolapse quantification in 91% of all cases at 1 year after surgery. Postvoid
      residual values significantly improved and remained stable for 1 year. Worse
      overactive bladder questionnaire score was a significant predictive factor for
      poor postoperative International Prostate Symptom Score. CONCLUSION: The tension
      free vaginal mesh plus transobturator tape procedure improves lower urinary tract
      symptoms in the majority of patients presenting pelvic organ prolapse.

PMID- 24112547
TI  - Ocular manifestations of monoclonal copper-binding immunoglobulin.
AB  - The dense accumulation of copper in Descemet membrane and lens capsule is the
      characteristic manifestation of a circulating monoclonal antibody with strong
      affinity for copper. The overproduction of this monoclonal immunoglobulin may be
      associated with either multiple myeloma or a benign monoclonal gammopathy.
      Despite prolonged exposure to elevated serum copper, no other tissues in the body
      are adversely affected by this redox metal. We describe the clinical and
      pathological findings in a 46-year-old woman with this disorder.

PMID- 24112548
TI  - Spontaneous recovery and treatment effects in patients with homonymous visual
      field defects: a meta-analysis of existing literature in terms of the ICF
      framework.
AB  - Homonymous visual field defects (HVFDs) are a common consequence of posterior
      brain injury. Most patients do not recover spontaneously and require
      rehabiliation. To determine whether a certain intervention may help an individual
      patient, it is necessary to predict the patient's level of functioning and the
      effect of specific training. We provide an overview of both the existing
      literature on HVFDs in terms of the International Classification of Functioning,
      Disability, and Health (ICF) components and the variables predicting the
      functioning of HVFD patients or the effect of treatment. We systematically
      analyzed 221 publications on HVFD. All variables included in these articles were
      classified according to the ICF, as developed by the World Health Organization,
      and checked for their predictive value. We found that ICF helps to clarify the
      scope of the existing literature and provides a framework for designing future
      studies, which should consider including more outcome measures related to
      Activities and Participation. Although several factors have been described that
      predict HVFD patients' level of functioning or the effects of training,
      additional research is necessary to identify more.

PMID- 24112549
TI  - Local chemotherapeutic agents for the treatment of ocular malignancies.
AB  - We critically analyze available peer-reviewed literature, including clinical
      trials and case reports, on local ocular cancer treatments. Recent innovations in
      many areas of ocular oncology have introduced promising new therapies, but, for
      the most part, the optimal treatment of ocular malignancies remains elusive.

PMID- 24112550
TI  - Mortality in perinatally HIV-infected young people in England following
      transition to adult care: an HIV Young Persons Network (HYPNet) audit.
AB  - OBJECTIVES: Mortality in young people with perinatally acquired HIV infection
      (PHIV) following transfer to adult care has not been characterized in the UK. We
      conducted a multicentre audit to establish the number of deaths and associated
      factors. METHODS: Fourteen adult clinics caring for infected young people
      reported deaths to 30 September 2011 on a proforma. Deaths were matched to the
      Collaborative HIV Paediatric Study, a clinical database of HIV-infected children
      in the UK/Ireland, to describe clinical characteristics in paediatric care of
      those who died post-transition. RESULTS: Eleven deaths were reported from 14
      clinics which cared for 248 adults with PHIV. For the 11 deaths, the median age
      at transfer to adult care was 17 years (range 15-21 years), and at death was 21
      years (range 17-24 years). Causes of death were suicide (two patients), advanced
      HIV disease (seven patients) and bronchiectasis (one patient), with one cause
      missing. At death, the median CD4 count was 27 cells/MUL (range 0-630 cells/MUL);
      five patients were on antiretroviral therapy (ART) but only two had a viral load
      < 50 HIV-1 RNA copies/mL. Nine had poor adherence when in paediatric care,
      continuing into adult care despite multidisciplinary support. Eight had ART
      resistance, although all had potentially suppressive regimens available. Nine had
      mental health diagnoses. CONCLUSIONS: Our findings highlight the complex medical
      and psychosocial issues faced by some adults with PHIV, with nine of the 11
      deaths in our study being associated with poor adherence and advanced HIV
      disease. Novel adherence interventions and mental health support are required for
      this vulnerable cohort.

PMID- 24112551
TI  - N6-isopentenyladenosine improves nuclear shape in fibroblasts from humans with
      progeroid syndromes by inhibiting the farnesylation of prelamin A.
AB  - Hutchinson-Gilford progeria syndrome is caused by mutations in the lamin A/C gene
      that lead to expression of a truncated, permanently farnesylated prelamin A
      variant called progerin. The accumulation of progerin at the nuclear envelope
      causes mis-shapen nuclei and results in progeroid syndromes. Previous studies in
      cells from individuals with Hutchinson-Gilford progeria syndrome have shown that
      blocking of farnesylation of prelamin A ameliorates the nuclear shape
      abnormalities. Here we observed that an inhibitor of farnesyl diphosphate
      synthase, N6-isopentenyladenosine, impeded the farnesylation of prelamin A,
      causing a decrease in the frequency of nuclear shape abnormalities and
      redistribution of prelamin A away from the inner nuclear envelope. A combination
      of lovastatin and N6-isopentenyladenosine significantly improved nuclear shape in
      fibroblast cell lines from atypical progeria patients. These findings establish a
      paradigm for ameliorating the most obvious cellular pathology in lamin-related
      progeroid syndromes, and suggest a potential strategy for treating children with
      Hutchinson-Gilford progeria syndrome.

PMID- 24112553
TI  - Re: androgen deprivation therapy: impact on quality of life and cardiovascular
      health.

PMID- 24112554
TI  - L (+)-lactic acid production by pellet-form Rhizopus oryzae NRRL 395 on biodiesel
      crude glycerol.
AB  - BACKGROUND: Given its availability and low price, glycerol derived from biodiesel
      industry has become an ideal feedstock for the production of fuels and chemicals.
      A solution to reduce the negative environmental problems and the cost of
      biodiesel is to use crude glycerol as carbon source for microbial growth media in
      order to produce valuable organic chemicals. In the present paper, crude glycerol
      was used as carbon substrate for production of L (+)-lactic acid using pelletized
      fungus R. oryzae NRRL 395 on batch fermentation. More, the experiments were
      conducted on media supplemented with inorganic nutrients and lucerne green juice.
      RESULTS: Crude and pure glycerols were first used to produce the highest biomass
      yield of R. oryzae NRRL 395. An enhanced lactic acid production then followed up
      using fed-batch fermentation with crude glycerol, inorganic nutrients and lucerne
      green juice. The optimal crude glycerol concentration for cultivating R. oryzae
      NRRL 395 was 75 g l(-1), which resulted in a fungal biomass yield of 0.72 g g(-1)
      in trial without lucerne green juice addition and 0.83 g g(-1) in trial with
      lucerne green juice. The glycerol consumption rate was 1.04 g l(-1) h(-1) after
      48 h in trial with crude glycerol 75 g l(-1) while in trial with crude glycerol
      10 g l(-1) the lowest rate of 0.12 g l(-1) h(-1) was registered. The highest L
      (+)-lactic acid yield (3.72 g g(-1)) was obtained at the crude glycerol
      concentration of 75 g l(-1) and LGJ 25 g l(-1), and the concentration of lactic
      acid was approximately 48 g l(-1). CONCLUSIONS: This work introduced sustainable
      opportunities for L (+)-lactic acid production via R. oryzae NRRL 395
      fermentation on biodiesel crude glycerol media. The results showed good fungal
      growth on crude glycerol at 75 g l(-1) concentration with lucerne green juice
      supplementation of 25 g l(-1). Lucerne green juice provided a good source of
      nutrients for crude glycerol fermentation, without needs for supplementation with
      inorganic nutrients. Crude glycerol and lucerne green juice ratio influence the L
      (+)-lactic acid production, increasing the lactate productivity with the
      concentration of crude glycerol.

PMID- 24112552
TI  - Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron
      assimilation mechanism linked to nitric oxide stress during early infection.
AB  - BACKGROUND: The initial interaction between host cell and pathogen sets the stage
      for the ensuing infection and ultimately determine the course of disease.
      However, there is limited knowledge of the transcripts utilized by host and
      pathogen and how they may impact one another during this critical step. The
      purpose of this study was to create a host-Mycobacterium avium subsp.
      paratuberculosis (MAP) interactome for early infection in an epithelium
      macrophage co-culture system using RNA-seq. RESULTS: Establishment of the host
      MAP interactome revealed a novel iron assimilation system for carboxymycobactin.
      Iron assimilation is linked to nitric oxide synthase-2 production by the host and
      subsequent nitric oxide buildup. Iron limitation as well as nitric oxide is a
      prompt for MAP to enter into an iron sequestration program. This new iron
      sequestration program provides an explanation for mycobactin independence in some
      MAP strains grown in vitro as well as during infection within the host cell.
      Utilization of such a pathway is likely to aid MAP establishment and long-term
      survival within the host. CONCLUSIONS: The host-MAP interactome identified a
      number of metabolic, DNA repair and virulence genes worthy for consideration as
      novel drug targets as well as future pathogenesis studies. Reported interactome
      data may also be utilized to conduct focused, hypothesis-driven research. Co
      culture of uninfected bovine epithelial cells (MAC-T) and primary bovine
      macrophages creates a tolerant genotype as demonstrated by downregulation of
      inflammatory pathways. This co-culture system may serve as a model to investigate
      other bovine enteric pathogens.

PMID- 24112556
TI  - Upper airway obstruction in Norwich Terriers: 16 cases.
AB  - BACKGROUND: Norwich Terriers have grown increasingly popular as show animals and
      pets, and awareness of respiratory problems within the breed is growing.
      OBJECTIVE: To describe components of obstructive upper airway syndrome in a
      nonbrachycephalic terrier breed. ANIMALS: Sixteen Norwich Terriers; 12 with and 4
      without clinical signs of respiratory disease. METHODS: Prospective case series.
      Physical and laryngoscopic examinations were performed by 1 investigator in all
      dogs. Medical and surgical interventions were summarized and results of follow-up
      examination or owner reports were recorded. RESULTS: The study population was
      comprised of 9 females (6 intact) and 7 males (5 intact). Median age was 3.0
      years (range, 0.5-11 years). Of 12 dogs presented for a respiratory complaint,
      physical examination was normal in 4 dogs. Laryngoscopic examination was abnormal
      in 11/12 dogs with redundant supra-arytenoid folds, laryngeal collapse, everted
      laryngeal saccules, and a narrowed laryngeal opening in most. Of 4 dogs lacking
      clinical signs, all had normal physical examination; however, 3/4 dogs had
      similar appearance of the larynx to dogs with clinical signs. Response to
      surgical intervention was minimal to moderate in all dogs. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Norwich Terriers suffer from an upper airway obstructive
      syndrome that differs from that encountered in brachycephalic breeds. Affected
      dogs are difficult to identify without laryngoscopic examination because of the
      lack of clinical signs and abnormalities in physical examination findings,
      despite severe airway obstruction. Care is warranted when anesthetizing Norwich
      Terriers because of the small size of the laryngeal opening.

PMID- 24112555
TI  - Highly diverse and spatially heterogeneous mycorrhizal symbiosis in a rare
      epiphyte is unrelated to broad biogeographic or environmental features.
AB  - Symbiotic interactions are common in nature. In dynamic or degraded environments,
      the ability to associate with multiple partners (i.e. broad specificity) may
      enable species to persist through fluctuations in the availability of any
      particular partner. Understanding how species interactions vary across landscapes
      is necessary to anticipate direct and indirect consequences of environmental
      degradation on species conservation. We asked whether mycorrhizal symbiosis by
      populations of a rare epiphytic orchid (Epidendrum firmum) is related to
      geographic or environmental heterogeneity. The latter would suggest that
      interactions are governed by environmental conditions rather than historic
      isolation of populations and/or mycorrhizal fungi. We used DNA-based methods to
      identify mycorrhizal fungi from eleven E. firmum populations in Costa Rica. We
      used molecular and phylogenetic analyses to compare associations. Epidendrum
      firmum exhibited broad specificity, associating with diverse mycorrhizal fungi,
      including six Tulasnellaceae molecular operational taxonomic units (MOTUs), five
      Sebacinales MOTUs and others. Notably, diverse mycorrhizal symbioses formed in
      disturbed pasture and roadside habitats. Mycorrhizal fungi exhibited significant
      similarity within populations (spatial and phylogenetic autocorrelation) and
      significant differences among populations (phylogenetic community dissimilarity).
      However, mycorrhizal symbioses were not significantly associated with
      biogeographic or environmental features. Such unexpected heterogeneity among
      populations may result from complex combinations of fine-scale environmental
      factors and macro-evolutionary patterns of change in mycorrhizal specificity.
      Thus, E. firmum exhibits broad specificity and the potential for opportunistic
      associations with diverse fungi. We suggest that these characteristics could
      confer symbiotic assurance when mycorrhizal fungi are stochastically available,
      which may be crucial in dynamic or disturbed habitats such as tropical forest
      canopies. 

PMID- 24112557
TI  - Antibodies to clustered acetylcholine receptor: expanding the phenotype.
AB  - BACKGROUND AND PURPOSE: To provide a detailed phenotypical description of
      seronegative patients with generalized myasthenia gravis and antibodies to
      clustered acetylcholine receptors (AChRs) and to assess their frequency amongst a
      French seronegative generalized myasthenia gravis (SNMG) population. METHODS: A
      French SNMG database was created and the sera from the 37 patients included in it
      were analysed by immunofluorescence of cell-based assays using cotransfection of
      AChR subunit genes together with rapsyn to densely cluster the AChRs. RESULTS:
      Sixteen per cent (n = 6) of the SNMG patients were found to have antibodies to
      clustered AChR. They presented either with early onset MG and thymic hyperplasia,
      late onset MG and thymic involution, or thymoma associated MG. They responded
      well to cholinesterase inhibitors and immunosuppressants. CONCLUSIONS: Patients
      with antibodies to clustered AChR account for a significant proportion of SNMG
      patients and resemble patients with AChR antibodies detected by standard radio
      immunoprecipitation.

PMID- 24112558
TI  - Effect of admission time on mortality in an intensive care unit in Mainland
      China: a propensity score matching analysis.
AB  - INTRODUCTION: The relationship between admission time and intensive care unit
      (ICU) mortality is inconclusive and influenced by various factors. This study
      aims to estimate the effect of admission time on ICU outcomes in a tertiary
      teaching hospital in China by propensity score matching (PSM) and stratified
      analysis. METHODS: A total of 2,891 consecutive patients were enrolled in this
      study from 1 January 2009 to 29 December 2011. Multivariate logistic regression
      and survival analysis were performed in this retrospective study. PSM and
      stratified analysis were applied for confounding factors, such as Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score and admission
      types. RESULTS: Compared with office hour subgroup (n = 2,716), nighttime (NT, n
      = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged
      length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of
      medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001)
      patients. Moreover, NT admissions were related to higher ICU mortality [odds
      ratio (OR), 1.725 (95% CI 1.118-2.744), P = 0.01] and elevated mortality risk at
      28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171-3.150), P = 0.01]. PSM showed
      that admission time remained related to ICU outcome (P = 0.045) and mortality
      risk at 28 days [OR, 2.187 (95% CI 1.119-4.271), P = 0.022]. However, no
      mortality difference was found between weekend and workday admissions (P =
      0.849), even if weekend admissions were more related to higher APACHE II scores
      compared with workday admissions. CONCLUSIONS: NT admission was associated with
      poor ICU outcomes. This finding may be related to shortage of onsite intensivists
      and qualified residents during NT. The current staffing model and training system
      should be improved in the future.

PMID- 24112559
TI  - Dental traumas during the military service.
AB  - BACKGROUND: Dental traumas are most frequent during the first three decades of
      life and more frequent among males than females. Approximately 80% (n = 28 000)
      of the male age cohort performs military service annually in Finland. As little
      is known of dental, head, and neck traumas during the military service, our aim
      was to study the etiology, number and occurrence of traumas of the Finnish
      conscripts during one calendar year. Our hypothesis was that above-mentioned
      traumas comprise a remarkable proportion of military accidents. MATERIALS AND
      METHODS: The data comprised of all the Finnish conscripts' trauma cases in the
      year 2009 (mean age 20.1 years, SD 1.1). The frequency, mechanism, and time of
      the incidences were analyzed. RESULTS: Of the total 1432 trauma cases, 303 (23%)
      involved head, neck, or dentition. The occurrence rate of dental traumas was 6.5
      cases/1000 persons/year. Dental traumas comprised 14.3% of all traumas. The most
      common mechanism for dental traumas was a blow-type force. First 4 months of the
      service and winter time were periods of increased risk of dental traumas. Two
      thirds of the dental traumas, one-third of the body traumas and a quarter of the
      head and neck traumas occurred during military field exercises. Most dental
      traumas required a visit to a military dental clinic and also needed follow-up
      care. DISCUSSION AND CONCLUSION: Head, neck, and dental injuries are common
      during the military service in Finland. Prevention of dental traumas and need for
      first aid dental skills of the personnel should be emphasized.

PMID- 24112560
TI  - Safety incidents involving confused and forgetful older patients in a specialised
      care setting--analysis of the safety incidents reported to the HaiPro reporting
      system.
AB  - AIMS AND OBJECTIVES: To describe the safety incidents involving confused and
      forgetful older patients in a specialised care setting entered in the HaiPro
      reporting system. BACKGROUND: About 10% of patients experience a safety incident
      during hospitalisation, which causes or could cause them harm. The possibility of
      a safety incident during hospitalisation increases significantly with age. A mild
      or moderate memory disorder and acute confusion are often present in the safety
      incidents originating with an older patient. DESIGN: The design of the study was
      action research with this study using findings from one of the first-phase
      studies, which included qualitative and quantitative analysed data. METHODS: Data
      were collected from the reporting system for safety incidents (HaiPro) in a
      university hospital in Finland. There were 672 reported safety incidents from
      four acute medical wards during the years 2009-2011, which were scrutinised.
      Seventy-five of them were linked to a confused patient and were analysed.
      RESULTS: The majority of the safety incidents analysed involved patient-related
      accidents. In addition to challenging behaviour, contributing factors included
      ward routines, shortage of nursing staff, environmental factors and staff
      knowledge and skills. Nurses tried to secure the patient safety in many different
      ways, but the modes of actions were insufficient. CONCLUSION AND RELEVANCE TO
      CLINICAL PRACTICE: Nursing staff need evidence-based information on how to assess
      the cognitive status of a confused patient and how to encounter such patients.
      The number of nursing staff and ward routines should be examined critically and
      put in proportion to the care intensity demands caused by the patient's confused
      state. The findings can be used as a starting point in the prevention of safety
      incidents and in improving the care of older patients.

PMID- 24112561
TI  - DNA barcoding of tropical black flies (Diptera: Simuliidae) of Thailand.
AB  - The ecological and medical importance of black flies drives the need for rapid
      and reliable identification of these minute, structurally uniform insects. We
      assessed the efficiency of DNA barcoding for species identification of tropical
      black flies. A total of 351 cytochrome c oxidase subunit 1 sequences were
      obtained from 41 species in six subgenera of the genus Simulium in Thailand.
      Despite high intraspecific genetic divergence (mean = 2.00%, maximum = 9.27%),
      DNA barcodes provided 96% correct identification. Barcodes also differentiated
      cytoforms of selected species complexes, albeit with varying levels of success.
      Perfect differentiation was achieved for two cytoforms of Simulium feuerborni,
      and 91% correct identification was obtained for the Simulium angulistylum
      complex. Low success (33%), however, was obtained for the Simulium siamense
      complex. The differential efficiency of DNA barcodes to discriminate cytoforms
      was attributed to different levels of genetic structure and demographic histories
      of the taxa. DNA barcode trees were largely congruent with phylogenies based on
      previous molecular, chromosomal and morphological analyses, but revealed
      inconsistencies that will require further evaluation. 

PMID- 24112562
TI  - Enzymes immobilized in mesoporous silica: a physical-chemical perspective.
AB  - Mesoporous materials as support for immobilized enzymes have been explored
      extensively during the last two decades, primarily not only for biocatalysis
      applications, but also for biosensing, biofuels and enzyme-controlled drug
      delivery. The activity of the immobilized enzymes inside the pores is often
      different compared to that of the free enzymes, and an important challenge is to
      understand how the immobilization affects the enzymes in order to design
      immobilization conditions that lead to optimal enzyme activity. This review
      summarizes methods that can be used to understand how material properties can be
      linked to changes in enzyme activity. Real-time monitoring of the immobilization
      process and techniques that demonstrate that the enzymes are located inside the
      pores is discussed by contrasting them to the common practice of indirectly
      measuring the depletion of the protein concentration or enzyme activity in the
      surrounding bulk phase. We propose that pore filling (pore volume fraction
      occupied by proteins) is the best standard for comparing the amount of
      immobilized enzymes at the molecular level, and present equations to calculate
      pore filling from the more commonly reported immobilized mass. Methods to detect
      changes in enzyme structure upon immobilization and to study the microenvironment
      inside the pores are discussed in detail. Combining the knowledge generated from
      these methodologies should aid in rationally designing biocatalyst based on
      enzymes immobilized in mesoporous materials. 

PMID- 24112563
TI  - Classification tree analysis to enhance targeting for follow-up exam of
      colorectal cancer screening.
AB  - BACKGROUND: Follow-up rate after a fecal occult blood test (FOBT) is low
      worldwide. In order to increase the follow-up rate, segmentation of the target
      population has been proposed as a promising strategy, because an intervention can
      then be tailored toward specific subgroups of the population rather than using
      one type of intervention for all groups. The aim of this study is to identify
      subgroups that share the same patterns of characteristics related to follow-up
      exams after FOBT. METHODS: The study sample consisted of 143 patients aged 50-69
      years who were requested to undergo follow-up exams after FOBT. A classification
      tree analysis was performed, using the follow-up rate as a dependent variable and
      sociodemographic variables, psychological variables, past FOBT and follow-up
      exam, family history of colorectal cancer (CRC), and history of bowel disease as
      predictive variables. RESULTS: The follow-up rate in 143 participants was 74.1%
      (n = 106). A classification tree analysis identified four subgroups as follows;
      (1) subgroup with a high degree of fear of CRC, unemployed and with a history of
      bowel disease (n = 24, 100.0% follow-up rate), (2) subgroup with a high degree of
      fear of CRC, unemployed and with no history of bowel disease (n = 17, 82.4%
      follow-up rate), (3) subgroup with a high degree of fear of CRC and employed (n =
      24, 66.7% follow-up rate), and (4) subgroup with a low degree of fear of CRC (n =
      78, 66.7% follow-up rate). CONCLUSION: The identification of four subgroups with
      a diverse range of follow-up rates for CRC screening indicates the direction to
      take in future development of an effective tailored intervention strategy.

PMID- 24112564
TI  - Membrane vesicle formation is associated with pyocin production under
      denitrifying conditions in Pseudomonas aeruginosa PAO1.
AB  - Many Gram-negative bacteria produce membrane vesicles (MVs) that serve as
      vehicles to mediate intraspecies and interspecies interactions. Despite their
      ubiquity in Gram-negative bacteria and their biological importance, how MV
      formation is regulated is poorly understood. Pseudomonas aeruginosa is a
      ubiquitous bacterium that is one of the most extensively studied model organism
      in MVs. Recent studies highlight the importance of a quorum-sensing signal,
      Pseudomonas quinolone signal (PQS), in the formation of MVs; however, PQS
      synthesis requires oxygen and is not produced under anoxic conditions. This
      situation leads to the question of MV production under anoxic conditions. Here,
      we examined whether MVs are produced under denitrifying conditions and what kind
      of factors are involved in the MV production under such condition. Under
      denitrifying condition, P. aeruginosa PAO1 produced a considerable amount of MVs.
      Interestingly, pyocin components were found to be accumulated in the isolated
      MVs. Pyocin-related protein mutants produced less MVs compared with the wild
      type. We further indicate that pyocin production is activated by nitric oxide, in
      which the SOS response is involved. This study presents a regulatory mechanism
      where pyocin is associated with MV production, and further implies how the
      environment impacts MV production in P. aeruginosa. 

PMID- 24112565
TI  - Prevalence and counts of Salmonella and enterohemorrhagic Escherichia coli in
      raw, shelled runner peanuts.
AB  - Three major outbreaks of salmonellosis linked to consumption of peanut butter
      during the last 6 years have underscored the need to investigate the potential
      sources of Salmonella contamination in the production process flow. We conducted
      a study to determine the prevalence and levels of Salmonella in raw peanuts.
      Composite samples (1,500 g, n = 8) of raw, shelled runner peanuts representing
      the crop years 2009, 2010, and 2011 were drawn from 10,162 retained 22-kg lot
      samples of raw peanuts that were negative for aflatoxin. Subsamples (350 g) were
      analyzed for the presence of Salmonella and enterohemorrhagic Escherichia coli.
      Salmonella was found in 68 (0.67%) of 10,162 samples. The highest prevalence rate
      (P < 0.05) was for 2009 (1.35%) compared with 2010 (0.36%) and 2011 (0.14%).
      Among four runner peanut market grades (Jumbo, Medium, No. 1, and Splits), Splits
      had the highest prevalence (1.46%; P < 0.05). There was no difference (P > 0.05)
      in the prevalence by region (Eastern versus Western). Salmonella counts in
      positive samples (most-probable-number [MPN] method) averaged 1.05 (range, 0.74
      to 5.25) MPN per 350 g. Enterohemorrhagic E. coli was found in only three samples
      (0.030%). Typing of Salmonella isolates showed that the same strains found in
      Jumbo and Splits peanuts in 2009 were also isolated from Splits in 2011.
      Similarly, strains isolated in 2009 were also isolated in 2010 from different
      peanut grades. These results indicated the persistence of environmental sources
      throughout the years. For five samples, multiple isolates were obtained from the
      same sample that had different pulsed-field gel electrophoresis types. This
      multistrain contamination was primarily observed in Splits peanuts, in which the
      integrity of the kernel is usually compromised. The information from the study
      can be used to develop quantitative microbial risk assessments models. 

PMID- 24112566
TI  - Antimicrobial drug resistance patterns among cattle- and human-associated
      Salmonella strains.
AB  - During the year 2004, 178 human and 158 bovine clinical Salmonella isolates were
      collected across New York State to better understand the transmission dynamics
      and genetic determinants of antimicrobial resistance among human and bovine
      hosts. Serotyping, sequence typing, and pulsed-field gel electrophoresis typing
      results have been reported previously. Here we tested all isolates for phenotypic
      susceptibility to 15 antimicrobial drugs that are part of the National
      Antimicrobial Monitoring System bovine susceptibility panel. PCR was performed on
      a representative subset of unique isolates (n = 53) to screen for the presence of
      21 known antimicrobial resistance genes (i.e., ampC, blaTEM-1, blaCMY-2, blaPSE
      1, cat1, cat2, cmlA, flo, aadA1, aadA2, aacC2, strA, strB, aphA1-IAB, dhrfI,
      dhrfXII, sulI, sulII, tetA, tetB, and tetG); selected fluoroquinolone- and
      nalidixic acid-resistant (n = 3) and -sensitive (n = 6) isolates were also tested
      for known resistance-conferring mutations in gyrA and parC. Genes responsible for
      antimicrobial resistance were shared among isolates of human and bovine origin.
      However, bovine isolates were significantly more likely than human isolates to be
      multidrug resistant (P < 0.0001; Fisher's exact test). Our analyses showed
      perfect categorical agreement between phenotypic and genotypic resistance for
      beta-lactam and chloramphenicol. Our data confirm that resistance profiles of
      amoxicillin-clavulanic acid, chloramphenicol, kanamycin, and tetracycline were
      strongly associated with the presence of blaCMY or ampC, flo, aphA1-IAB, and
      tetA, respectively. Our findings provide evidence for the clinical value of
      genotypic resistance typing if incorporating multiple known genes that can confer
      a phenotypic resistance profile. 

PMID- 24112567
TI  - Method for the detection of priority Shiga toxin-producing Escherichia coli in
      beef trim.
AB  - A method has been developed for the detection in beef trim of priority Shiga
      toxin-producing E. coli (STEC) strains, defined as E. coli possessing the
      virulence factors stx1 and/or stx2 and intimin (eae), with O serogroups O26, O45,
      O103, O111, O121, O145, or O157. The method is based on recovery of the target
      bacteria by overnight enrichment in a broth optimized for recovery of O157 and
      non-O157 STEC, followed by screening using multiplex PCR techniques targeting (i)
      stx1, stx2, and eae (STE PCR) and (ii) gene sequences associated with the seven
      priority O serogroups (Poly O PCR), and then direct plating of broth samples
      positive in both STE and Poly O PCR onto Rainbow agar. Colonies on agar media
      were screened batchwise for STEC by the STE PCR, and presumptive isolates were
      characterized using a multiplex PCR and cloth-based hybridization array system
      targeting key virulence and O serogroup-specific markers. Using one
      representative strain of each priority O serogroup individually inoculated in
      beef trim samples, the method exhibited a limit of detection approaching 1 to 2
      viable STEC cells per 65 g. None of the uninoculated trim samples produced
      positive results with either of the screening PCR procedures or on analysis of
      colonies recovered on plating media. STEC-negative samples were readily
      identified by screening PCR within 24 h, with a turnaround time of fewer than 4
      days for confirmation of positives. The inclusivity and exclusivity
      characteristics of the screening PCR techniques were verified using a total of 65
      different priority STEC strains: 24 nonpriority STEC, 15 non-STEC bacteria, and
      only those strains bearing the targeted characteristics produced screening PCR
      positive results. 

PMID- 24112568
TI  - Occurrence of zoonotic clostridia and Yersinia in healthy cattle.
AB  - Zoonotic pathogens are a frequent cause of disease worldwide. This study was
      designed to determine the occurrence of Clostridium difficile, Clostridium
      botulinum, and Yersinia enterocolitica in cattle in southern Bavaria, Germany.
      The study population included 49 farms; 34 were dairy farms (30 also fattening
      beef cattle) and 15 were solely beef cattle farms. Fecal and dust samples were
      collected from summer 2011 to summer 2012 and analyzed using a combination of
      enrichment procedures and real-time PCR. For the detection of C. difficile,
      samples were screened for the presence of the tpi gene and toxin genes tcdA,
      tcdB, and cdtA. Samples also were screened for genes for C. botulinum toxins A
      through F and for the ail gene of Y. enterocolitica. Of 506 samples, C. difficile
      genes were found in 29 samples (5.7%): 25 samples from dairy farms and 4 samples
      from beef cattle farms. Toxin genes were identified in 17 samples, with toxigenic
      profiles of A(+)B(+)CDT(-), A(+)B(-)CDT(+), and A(+)B(+)CDT(+). C. botulinum
      toxin genes were not detected in fecal samples from cattle, but the gene for
      toxin B was detected in 1 (0.8%) of 125 dust samples. Y. enterocolitica genes
      were found in 6 (1.6%) of 382 fecal samples from three dairy farms and one beef
      cattle farm. This study revealed that C. difficile and Y. enterocolitica are rare
      on cattle farms in Bavaria, Germany. In contrast to results of previous studies,
      C. botulinum was not detected in fecal samples but was found very rarely in dust
      samples from the cattle environment. 

PMID- 24112569
TI  - Campylobacter spp., Yersinia enterocolitica, and Salmonella enterica and their
      simultaneous occurrence in German fattening pig herds and their environment.
AB  - Campylobacter spp., Salmonella enterica, and Yersinia enterocolitica are common
      causes of foodborne infections in humans with pork as a potential source.
      Monitoring programs at farm level are, to date, only implemented for S. enterica,
      while epidemiological knowledge of the other two pathogens is still lacking. This
      study aimed to assess the pathogen load (in the pigs' environment) in fattening
      pig herds, their simultaneous occurrence, and the occurrence of Campylobacter
      spp. and Y. enterocolitica in herds in different Salmonella risk categories. In
      50 fattening pig herds in northern Germany, four pooled fecal samples and 10 swab
      samples from the pigs' direct environment (pen walls, nipple drinkers), indirect
      environment (hallways, drive boards), and flies and rodent droppings were
      collected from each herd and submitted for cultural examination. Campylobacter
      spp. were detected in 38.1% of fecal, 32.7% of direct environment, 5.3% of
      indirect environment, and 4.6% of flies/pests samples collected, and Y.
      enterocolitica in 17.1, 8.1, 1.2, and 3.1% and S. enterica in 11.2, 7.7, 4.1, and
      1.5%, respectively. For Campylobacter spp., Y. enterocolitica, and S. enterica,
      80, 48, and 32% of herds were positive, respectively; 22 herds were positive for
      both Campylobacter spp. and Y. enterocolitica, 12 for Campylobacter spp. and S.
      enterica, and 7 for Y. enterocolitica and S. enterica. There was no significant
      association between the pathogens at herd level. Campylobacter spp. and Y.
      enterocolitica were found more often in samples from the low Salmonella risk
      category (odds ratio, 0.51; confidence interval, 0.36 to 0.73, and 0.3, 0.17 to
      0.57), and this was also the case for Y. enterocolitica at herd level (odds
      ratio, 0.08; confidence interval, 0.02 to 0.3). This study provides evidence that
      the pigs' environment should be accounted for when implementing control measures
      on farms against Campylobacter spp. and Y. enterocolitica. An extrapolation from
      the current Salmonella monitoring to the other two pathogens does not seem
      feasible. 

PMID- 24112570
TI  - Modeling the thermoultrasound inactivation of Vibrio parahaemolyticus in raw
      peeled shrimps.
AB  - Vibrio parahaemolyticus has been identified as a causative agent for seafoodborne
      diseases worldwide. The effect of thermoultrasound treatment on the survival of
      V. parahaemolyticus in raw peeled shrimps was investigated in this study as an
      alternative bacterial inactivation method in seafood as part of the postharvest
      washing process. Raw peeled shrimps inoculated with V. parahaemolyticus were
      treated with mild heat (47, 50, and 53 degrees C) combined with ultrasound (0,
      96, 150, and 204 W) based on a 3 * 4 full factorial design, and the bacterial
      survival curves were fitted with a Weibull model. Because of the high
      correlations of the shape parameter n and the scale parameter beta in the Weibull
      model, an overall n was estimated from the whole set of bacterial inactivation
      data and beta values were estimated for each set of inactivation curves
      accordingly. A response surface model was generated to describe the scale
      parameter as a function of temperature and ultrasonic power. The results
      indicated that the Weibull model with the overall n value could be used to
      describe the bacterial reduction with the time of exposure to the
      thermoultrasound treatments, which was well supported by the small root mean
      square errors (RMSE) and the high coefficients of determination (R(2)). The
      quadratic model was validated with independent experiments within the prediction
      range. Statistical indices (R(2) = 0.99; P < 0.0001; RMSE = 0.17) and validation
      parameters (bias factor = 0.97; accuracy factor = 1.03) indicated satisfactory
      performance of the quadratic model. The results indicated that the
      thermoultrasound treatment is effective, simple, and cost-effective for
      inactivation of V. parahaemolyticus in shrimps during the postharvest washing
      process. 

PMID- 24112571
TI  - Effect of Mentha spicata L. and Artemisia campestris extracts on the shelf life
      and quality of vacuum-packed refrigerated sardine (Sardina pilchardus) fillets.
AB  - The present study investigated the effects of ethanolic extracts obtained from
      Mentha spicata and Artemisia campestris on the shelf life and the quality of
      vacuum-packed sardine fillets stored at 3 +/- 1 degrees C for a period of 21
      days. The three groups were tested were VC, control group; VM, group treated with
      1 % mint extract; and VA, group treated with 1 % artemisia extract. The observed
      shelf life of sardine fillets was 10 days for control samples, whereas the
      combination of vacuum packaging with mint and artemisia extracts extended the
      product's shelf life to 17 days. Among the chemical indices determined, the
      thiobarbituric acid-reactive substances values were significantly lower in VM
      samples. Total volatile base nitrogen was maintained at low levels in VA samples
      until 17 days of chilled storage. Results of aerobic plate counts and coliform
      counts showed the existence of a reduced growth in VA group, whereas lactic acid
      bacteria did not show a significant difference among groups. Natural extract
      treatments combined with vacuum packaging showed lower microbiological and
      chemical indices, indicating that the presence of phenolic compounds in mint and
      artemisia extracts and the removal of oxygen in the pack retarded lipid oxidation
      and reduced the growth of microorganisms, which resulted in preventing spoilage
      and extending the product's shelf life. 

PMID- 24112572
TI  - Meta-analysis of Campylobacter spp. survival data within a temperature range of 0
      to 42 degrees C.
AB  - In Europe, Campylobacter is the leading reported cause of bacterial foodborne
      infectious disease. Quantifying its ability to survive at chilled and ambient
      temperatures and identifying the factors involved in variation in its survival
      may contribute to the development of efficient risk management strategies. A data
      set of 307 inactivation curves collected from the literature and the ComBase
      database, combined with 388 experimental curves, was analyzed with a log-linear
      model to obtain 695 D-values (time for 1 log inactivation). An additional 146 D
      values collected from the literature or ComBase were added to the data set, for a
      total of 841 D-values. Because data were collected from different studies, the
      experimental conditions were somewhat heterogeneous (e.g., type of media or
      strain used). The full data set was then split into 19 different study types on
      which a meta-analysis was performed to determine the effect of temperature (range
      0 to 42 degrees C), Campylobacter species (C. coli and C. jejuni), and media
      (liquid media or meat matrix) on the survival ability of Campylobacter. A mixed
      effects model, in which the study type and bacterial species were considered as
      random effects and the media and temperature as fixed effects, was run using a
      Bayesian approach. Overall, the model gave satisfactory results, with a residual
      standard deviation of 0.345 (the model response was the log D-value, expressed in
      days). In addition, the survival of Campylobacter was greater at 0 than at 42
      degrees C, with a log-linear pattern; the z-value (temperature to have a 10-fold
      decrease of D-value) was estimated to be 26.4 degrees C (95 % interval: 23.9 to
      29.4 degrees C). Despite a significant media-species interaction term, it was
      established that both species were more resistant on the meat matrix than in
      liquid media. These results may be used to understand how Campylobacter can
      survive along the food chain, particularly in chilled environments, and
      consequently be transferred to other foodstuffs. 

PMID- 24112573
TI  - Inhibition of cytotoxicity of Shiga toxin of Escherichia coli O157:H7 on vero
      cells by Prosopis alba Griseb (Fabaceae) and Ziziphus mistol Griseb (Rhamnaceae)
      extracts.
AB  - The capacity of Prosopis alba Griseb. and Ziziphus mistol Griseb. fruit extracts
      to inhibit the toxic action of Shiga toxin (Stx) was investigated. Purification
      of Stx from Escherichia coli O157:H7 was performed by saline precipitation and
      affinity chromatography using a column with globotriaosylceramide, while the
      fruits were subjected to ethanolic or aqueous extractions. The protective action
      of both fruits was determined by pre-, co-, and postincubation of one 50%
      cytotoxic dose per ml of Stx with different concentrations of ethanolic and
      aqueous extracts in confluent monolayers of Vero cells for 72 h at 37 degrees C
      (5% CO2). The inhibition of the cytotoxic effect of Stx by fruit extracts was
      determined by the neutral red vital staining technique. The extraction of the
      polyphenols and flavonoids was effective, and more polyphenols per milligram of
      dissolved solids were obtained from P. alba than from Z. mistol. However, there
      were more flavonoids in Z. mistol than in P. alba. Components of both fruits
      increased the viability of cells treated with Stx when the extracts were
      preincubated with Stx for 1 h before being applied to the cell cultures, with the
      ethanolic extract of P. alba showing 95% cell viability at a concentration of
      2.45 mg/ml. The extracts were less effective in protecting cells when Stx,
      extracts, and cells were coincubated together without a previous incubation of
      Stx; only the concentrations of 19.46 mg/ml for the P. alba aqueous extract and
      3.75 mg/ml for the Z. mistol ethanolic extract resulted in the inhibition of
      cytotoxicity, with 52 and 56% cell viability occurring, respectively.
      Investigation into this difference in the protection of cells indicated that the
      protein molecule of Stx suffered degradation to advanced oxidative protein
      products during preincubation with extracts, principally with P. alba, which
      exhibited a greater amount of nonflavonoid polyphenols than Z. mistol. The
      prooxidant action on Stx favored the cells and enhanced the protective action of
      both fruits. 

PMID- 24112574
TI  - Cell-free preparations of Lactobacillus acidophilus strain La-5 and
      Bifidobacterium longum strain NCC2705 affect virulence gene expression in
      Campylobacter jejuni.
AB  - Campylobacter spp. are among the most commonly reported bacterial causes of acute
      diarrheal disease in humans worldwide. Potential virulence factors include
      motility, chemotaxis, colonization ability, adhesion to intestinal cells,
      invasion and epithelial translocation, intracellular survival, and formation of
      toxins. Probiotic Lactobacillus and Bifidobacterium strains are known to have an
      inhibitory effect against the growth of various foodborne pathogens. The
      objective of this study was to investigate the effect of Lactobacillus
      acidophilus strain La-5 and Bifidobacterium longum strain NCC2705 cell-free spent
      media (CFSM) on the expression of virulence genes (cadF, cdtB, flaA, and ciaB) of
      Campylobacter jejuni strain 81-176 and a luxS mutant, using real-time PCR. Our
      results demonstrated that the CFSM of both probiotic strains were able to down
      regulate the expression of ciaB (ratio of -2.80 and -5.51, respectively) and flaA
      (ratio of -7.00 and -5.13, respectively) in the wild-type Campylobacter strain.
      In the luxS mutant, where the activated methyl cycle is disrupted, only the ciaB
      gene (ratio -7.21) was repressed in the presence of La-5 CFSM. A supplementation
      of homocysteine to restore the disrupted cycle was able to partially reestablish
      the probiotic effect of both strains. luxS and the activated methyl cycle might
      play an active role in the modulation of virulence of C. jejuni by probiotic
      extracts. 

PMID- 24112575
TI  - Origanum vulgare subsp. hirtum essential oil prevented biofilm formation and
      showed antibacterial activity against planktonic and sessile bacterial cells.
AB  - Essential oils from six different populations of Origanum vulgare subsp. hirtum
      were compared for their antibiofilm properties. The six essential oils (A to F)
      were characterized by a combination of gas chromatography with flame ionization
      detector and gas chromatography with mass spectrometer detector analyses. All
      oils showed weak activity against the planktonic form of a group of
      Staphylococcus aureus strains and against a Pseudomonas aeruginosa ATCC 15442
      reference strain. The ability to inhibit biofilm formation was investigated at
      sub-MIC levels of 200, 100, and 50 m g/ml by staining sessile cells with
      safranin. Sample E showed the highest average effectiveness against all tested
      strains at 50 m g/ml and had inhibition percentages ranging from 30 to 52%. In
      the screening that used preformed biofilm from the reference strain P.
      aeruginosa, essential oils A through E were inactive at 200 m g/ml; F was active
      with a percentage of inhibition equal to 53.2%. Oregano essential oil can inhibit
      the formation of biofilms of various food pathogens and food spoilage organisms. 

PMID- 24112576
TI  - Inhibition of spoiling yeasts of fruit juices through citrus extracts.
AB  - This article reports on the bioactivities of citrus extracts (citrus extract,
      lemon extract, and neroli) toward Saccharomyces cerevisiae, Zygosaccharomyces
      bailii, Zygosaccharomyces rouxii, Pichia membranifaciens, and Rhodotorula
      bacarum. The bioactivities of the extracts (from 10 to 100 ppm) were evaluated
      through a microdilution method; thereafter, citrus extracts (0 to 80 ppm) were
      tested in combination with either pH (3.0 to 5.0) or temperature (5 to 25 degrees
      C). Finally, a confirmatory experiment was run in a commercial drink (referred to
      as red fruit juice) containing citrus extract (40 ppm) that was inoculated with
      either S. cerevisiae or Z. bailii (5 log CFU/ml) and stored at 4 and 25 degrees
      C. Yeasts increased to 7 log CFU/ml (Z. bailii) or 8 log CFU/ml (S. cerevisiae)
      in the control at 25 degrees C, but the citrus extract addition controlled yeast
      growth for at least 3 days; under refrigeration, the effect was significant for
      10 days. 

PMID- 24112577
TI  - Inactivation of Penicillium digitatum and Penicillium italicum under in vitro and
      in vivo conditions by using UV-C light.
AB  - In this study, the effects of UV-C on two of the main wound pathogens of citrus
      fruits, Penicillium digitatum and Penicillium italicum, were investigated with
      different inoculation methods in vitro and on oranges. P. digitatum and P.
      italicum spores were inoculated onto the surface of potato dextrose agar or
      oranges using spread, spot, wound, and piercing inoculation methods. UV-C
      treatment for 1 min from a working distance of 8 cm reduced the numbers of P.
      italicum and P. digitatum by about 3.9 and 5.3 log units, respectively, following
      spread inoculation under in vitro conditions. Significant reductions were
      obtained after 1-min UV-C treatments of the tested fungi following inoculation
      using the spread and spot methods. With inoculation by the wound and piercing
      methods, the tested spores were not inactivated completely even after 10- and 20
      min treatment times, respectively. The application of UV-C (7.92 kJ m(-2)) on
      oranges reduced the percentage of oranges infected at least threefold compared
      with the rate of infection in the untreated control samples. UV-C irradiation
      could effectively inactivate spores of P. italicum and P. digitatum inoculated by
      the spread plate and spot inoculation methods under in vitro and in vivo
      conditions. On the other hand, because of the low penetration ability of UV-C
      light, the tested fungi were not completely inactivated following inoculation
      with the wound and piercing methods. UV-C treatment has potential for use in
      surface decontamination of citrus fruits. 

PMID- 24112578
TI  - Evaluation of levulinic acid and sodium dodecyl sulfate as a sanitizer for use in
      processing Georgia-grown cantaloupes.
AB  - Freshly harvested Georgia-grown cantaloupes (Cucumis melo L. var. reticulatus cv.
      Athena and Atlantis) were spot inoculated with 100 MUl of a five-strain mixture
      of Salmonella enterica serovar Poona (9 log CFU/ml) at the stem scar and on the
      netted rind and then subjected to no treatment (control) or a 6-min treatment
      (tank only) in water, 120 ppm of chlorine (pH 7.0), 1% levulinic acid plus 0.1%
      sodium dodecyl sulfate (SDS; pH 3.0), or 2% levulinic acid plus 0.2% SDS (pH
      3.0). The log reduction for the tank-only treatments was 0.31, 0.59, 1.32, and
      1.37 log CFU/g at the stem scar and 0.97, 1.59, 2.06. and 3.37 log CFU/g on the
      netted rind for water, chlorine, 1% levulinic acid plus 0.1% SDS, and 2%
      levulinic acid plus 0.2% SDS, respectively. A greater log reduction was observed
      for the cantaloupe surface tissue with the water, chlorine, and 2% levulinic acid
      plus 0.2% SDS treatments when additional sanitizer (2 ml) and brushing (to
      simulate cantaloupes tumbling over brushes on the processing line) were added to
      the dump tank treatment. The stem scar tissue reductions were 0.90, 1.69, and
      1.53 log CFU/g, whereas the netted rind reductions were 1.56, 2.50, and 4.47 log
      CFU/g after treatment with water, chlorine, and 2% levulinic acid plus 0.2% SDS,
      respectively. These data suggest that 2% levulinic acid plus 0.2% SDS is
      effective for reducing Salmonella on the netted rind surface of cantaloupes.
      However, neither 2% levulinic acid plus 0.2% SDS nor 120 ppm of chlorine
      substantially reduced Salmonella on stem scar tissue. 

PMID- 24112579
TI  - Prevalence and characteristics of Escherichia coli strains producing extended
      spectrum beta -lactamases in slaughtered animals in the Czech Republic.
AB  - Resistance of bacteria to antibiotics is a global medical problem requiring close
      cooperation between veterinary and human physicians. Raw materials and foods of
      animal origin may be not only a source of pathogenic bacteria causing alimentary
      tract infections but also a source of bacteria with a dangerous extent of
      resistance to antibiotics, potentially entering the human food chain. This
      article presents results of the first study in the Czech Republic detecting the
      presence of Enterobacteriaceae-producing extended-spectrum b -lactamases (ESBLs)
      in swabs collected in slaughterhouses from surfaces of healthy animal carcasses.
      In 2012, swabs taken from pig (n = 166) and cattle (n = 140) carcass surfaces
      were analyzed. In 17 % of 53 studied slaughterhouses, ESBL-producing Escherichia
      coli strains were isolated. ESBLs were found in 11 and 4 % of porcine and bovine
      samples, respectively. Swabs collected from pigs yielded 18 ESBL-producing E.
      coli strains. The bla genes were found to encode production of CTX-M-1 group
      enzymes in 16 strains, SHV in one case, and both CTX-M-1-like and TEM in another
      case. In swabs taken from cattle, five ESBL-producing E. coli strains were
      isolated. In three cases, the bla genes for CTX-M-1-like production were
      identified; in two cases, genes for both CTX-M-1-like and TEM production were
      found. The similarity/identity of ESBL-positive isolates was compared by pulsed
      field gel electrophoresis. This is the first report and characterization of the
      presence and nature of ESBL-producing E. coli in swabs collected from surfaces of
      healthy pig and cattle carcasses in slaughterhouses in the Czech Republic. 

PMID- 24112580
TI  - Survivability of Escherichia coli O157:H7 in mechanically tenderized beef steaks
      subjected to lactic acid application and cooking under simulated industry
      conditions.
AB  - Mechanical tenderization improves the palatability of beef; however, it increases
      the risk of translocating pathogenic bacteria to the interior of beef cuts. This
      study investigated the efficacies of lactic acid spray (LA; 5 % ), storage, and
      cooking on the survivability of Escherichia coli O157:H7 in mechanically
      tenderized beef steaks managed under simulated industry conditions. Beef
      subprimals inoculated with either high (10(5) CFU/ml) or low (10(3) CFU/ml)
      levels of E. coli O157:H7 were treated (LA or control) and stored for 21 days
      prior to mechanical tenderization, steak portioning (2.54 cm), and additional
      storage for 7 days. Steaks were then cooked to an internal temperature of 55, 60,
      65, 70, or 75 degrees C. Samples were enumerated and analyzed using DNA-based
      methods. Treatment with LA immediately reduced E. coli O157:H7 on the lean and
      fat surfaces of high- and low-inoculum-treated subprimals by more than 1.0 log
      CFU/cm(2) (P < 0.05). Storage for 21 days reduced surface populations of E. coli
      O157:H7 regardless of the inoculation level; however, the populations on LA- and
      control-treated lean surfaces of high- and low-inoculum-treated subprimals were
      not different after 21 days (P > 0.05). E. coli O157:H7 was detected in core
      samples from high-inoculum-treated steaks cooked to 55, 60, or 70 degrees C.
      Conversely, E. coli O157:H7 was not detected in core samples from low-inoculum
      treated steaks, regardless of the internal cooking temperature. These data
      suggest that LA- and storage-mediated reduction of pathogens on subprimals
      exposed to typical industry contamination levels (10(1) CFU/cm(2)) reduces the
      risk of pathogen translocation and subsequent survival after cooking. 

PMID- 24112581
TI  - Biofilm formation of Salmonella serotypes in simulated meat processing
      environments and its relationship to cell characteristics.
AB  - Salmonella attached to meat contact surfaces encountered in meat processing
      facilities may serve as a source of cross-contamination. In this study, the
      influence of serotypes and media on biofilm formation of Salmonella was
      investigated in a simulated meat processing environment, and the relationships
      between biofilm formation and cell characteristics were also determined. All six
      serotypes (Salmonella enterica serotype Heidelberg, Salmonella Derby, Salmonella
      Agona, Salmonella Indiana, Salmonella Infantis, and Salmonella Typhimurium) can
      readily form biofilms on stainless steel surfaces, and the amounts of biofilms
      were significantly influenced by the serotypes, incubation media, and incubation
      time used in this study. Significant differences in cell surface hydrophobicity,
      autoaggregation, motility, and growth kinetic parameters were observed between
      individual serotypes tested. Except for growth kinetic parameters, the cell
      characteristics were correlated with the ability of biofilm formation incubated
      in tryptic soy broth, whereas no correlation with biofilm formation incubated in
      meat thawing-loss broth (an actual meat substrate) was found. Salmonella grown in
      meat thawing-loss broth showed a "cloud-shaped" morphology in the mature biofilm,
      whereas when grown in tryptic soy broth it had a "reticulum-shaped" appearance.
      Our study provides some practical information to understand the process of
      biofilm formation on meat processing contact surfaces. 

PMID- 24112582
TI  - Detecting Salmonella serovars in shell eggs by loop-mediated isothermal
      amplification.
AB  - Shell eggs contaminated with Salmonella Enteritidis pose serious food safety and
      public health concerns. More vigilant product testing calls for rapid, accurate,
      and reliable detection methods for Salmonella. Two loop-mediated isothermal
      amplification (LAMP) assays targeting different regions of the Salmonella
      invasion protein (encoded by invA) have been reported. In this study, performance
      of the two LAMP assays was compared with that of PCR in detecting Salmonella
      Enteritidis and Salmonella Typhimurium strains in experimentally contaminated egg
      homogenates. Both LAMP assays were highly specific. The detection limits were
      approximately 1 CFU per reaction for both Salmonella serovars in pure culture,
      100-fold more sensitive than that of PCR. Standard curves generated suggested a
      good linear relationship between Salmonella cell numbers and LAMP turbidity
      signals. In spiked egg homogenate, the LAMP assays could detect both Salmonella
      serovars down to 10(4) CFU/25 ml without enrichment and 10(0) CFU/25 ml with 8-h
      enrichment. In contrast, PCR was unable to detect either Salmonella serovar in
      egg homogenates spiked with less than 10(6) CFU/25 ml by direct testing and
      required at least 12 h of enrichment for samples spiked with 10(1) CFU/25 ml and
      24 h for those with 10(0) CFU/25 ml. The complete LAMP assay took about 10 h
      (including 8 h of enrichment) to complete. In conclusion, the two LAMP assays
      were rapid, accurate, and reliable methods for detecting Salmonella serovars in
      shell eggs and may be adopted in routine egg testing for Salmonella to improve
      egg safety and protect public health. 

PMID- 24112583
TI  - Prevalence and genetic characterization of Vibrio vulnificus in raw seafood and
      seawater in Malaysia.
AB  - Vibrio vulnificus is a highly invasive human pathogen that exists naturally in
      estuarine environment and coastal waters. In this study, we used different PCR
      assays to detect V. vulnificus in 260 seafood and 80 seawater samples. V.
      vulnificus was present in about 34 (13%) of the 260 seafood samples and 18 (23%)
      of the 80 seawater samples. Repetitive extragenic palindromic PCR (REP-PCR) and
      enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) were applied to
      subtype the V. vulnificus isolates. Twenty-five REP profiles and 45 ERIC profiles
      were observed, and the isolates were categorized into 9 and 10 distinct clusters
      at the similarity of 80%, by REP-PCR and ERIC-PCR, respectively. ERIC-PCR is more
      discriminative than REP-PCR in subtyping V. vulnificus, demonstrating high
      genetic diversity among the isolates. 

PMID- 24112584
TI  - Survival of Listeria monocytogenes during Production and ripening of traditional
      Turkish Savak tulum cheese and in synthetic gastric fluid.
AB  - This study investigated the survival and acid tolerance of Listeria monocytogenes
      during the 2-day processing stage and 90-day ripening of Savak tulum cheese, a
      traditional cheese in Turkey. Experimental Savak tulum cheese was produced from
      raw sheep's milk that was inoculated with a L. monocytogenes mixture consisting
      of five strains (average 7.0 log CFU/ml) and was ripened at 6 degrees C for 90
      days. Microbiological and chemical analyses and acid exposure experiments in
      synthetic gastric fluid (SGF) (pH 1.5 to 2.5) were carried out on days 1 and 2
      during processing and on days 0, 15, 30, 45, 60, and 90 during ripening. The
      numbers of L. monocytogenes did not decrease during processing, but a total of
      4.1 log CFU/g reduction was observed during ripening. Throughout the ripening
      period, L. monocytogenes cells survived direct 90-min exposures of the cheese
      samples to SGF. These results suggest that, although the pathogen numbers
      decreased in Savak tulum cheese ripened at 6 degrees C for 90 days, a sublethal
      environment may have occurred in the cheese during the production stage,
      activating the acid-tolerance mechanisms of the pathogen and allowing L.
      monocytogenes to maintain its viability in the SGF for 90 min. 

PMID- 24112585
TI  - Biocide and copper tolerance in enterococci from different sources.
AB  - Antimicrobial resistance in enterococci is a matter of concern. A collection of
      272 strains (including 107 Enterococcus faecalis and 165 Enterococcus faecium
      strains) isolated from meat and dairy products, seafood, vegetable foods,
      wildflowers, animal feces (ewe, goat, horse, mule), and hospitals were tested for
      sensitivity to biocides of different classes (quaternary ammonium compounds, a
      bisphenol, and a biguanide) and copper sulfate. Most isolates were inhibited at
      25 mg of benzalkonium chloride or cetrimide per liter or at 2.5 mg of
      hexadecylpyridinium chloride per liter. Few isolates had MICs higher than 25
      mg/liter for benzalkonium chloride (2.2%), cetrimide (0.74%), or
      hexadecylpyridinium chloride (0.37%), although they were all inhibited at 250
      mg/liter. The population response to triclosan was very homogeneous, and most
      isolates (98.16%) were inhibited at 250 mg of triclosan per liter. Chlorhexidine
      showed the greatest variability, with MICs in a range from 2.5 to 2,500 mg/liter.
      Remarkably, 74.57% of isolates from clinical samples required 2,500 mg of
      chlorhexidine per liter for inhibition, compared to much-lower concentrations
      required for most isolates from other sources. Enterococci were inhibited by
      copper sulfate in a concentration range from 4 to 16 mM, with no bimodal
      distribution. However, most isolates required 12 mM (41.91%) or 16 mM (47.43%)
      for inhibition. The highest percentages of isolates requiring 16 mM CuSO4 were
      from vegetable foods, seafood, and wildflowers. The results from the present
      study suggest intermediate levels of copper tolerance and a low incidence of
      biocide tolerance in the enterococci investigated, except for chlorhexidine in
      clinical isolates. 

PMID- 24112586
TI  - Norovirus: a growing cause of gastroenteritis in catalonia (Spain)?
AB  - Infectious acute gastroenteritis (AGE) is a major health problem worldwide.
      Salmonella is a leading cause of AGE outbreaks, but viruses may be responsible
      for up to 80% of cases. We compared the frequency and characteristics of AGE out
      breaks in Catalonia due to norovirus and Salmonella and the changes in these
      outbreaks from 2000 through 2010. In 2006 through 2010, we also investigated the
      distribution by season, setting, and implicated food, the incidence rates of
      cases associated, and the hospitalization rates. Differences in proportions were
      estimated by Pearson's chi-square test, and the odds ratio (OR) and 95%
      confidence interval (CI) were calculated. In 2000 through 2010, the number of AGE
      outbreaks caused by Salmonella decreased and those caused by norovirus
      significantly increased. From 2006 onward, norovirus was the most common etiology
      in AGE outbreaks, but in foodborne outbreaks, Salmonella was the more common
      cause until 2010. The incidence rate per 10(5) inhabitants was greater for
      norovirus (20.81 versus 3.97, P < 0.001), and the hospitalization rate was lower
      for norovirus (0.84 versus 4.69, P < 0.001). Salmonella infections occurred more
      frequently in the warmer months, and norovirus infections were more common in the
      colder months, both in terms of total outbreaks (OR = 4.50; 95% CI, 2.85 to 7.11;
      P < 0.001) and foodborne outbreaks (OR = 4.38; 95% CI, 2.42 to 7.95; P < 0.001).
      Norovirus infections were less common in private homes (OR = 0.08; 95% CI, 0.04
      to 0.14; P < 0.001) and more common in nursing homes (P < 0.001) and hospitals or
      long-term care facilities (OR = 14.09; 95% CI, 3.35 to 59.33; P < 0.001). Foods
      most frequently implicated in norovirus infection outbreaks were seafood (22% ;
      OR = 7.89; 95% CI, 2.59 to 24.3; P < 0.001), and those most common in Salmonella
      infection outbreaks were mayonnaise and similar items (30.2%; OR = 0.05; 95% CI,
      0.01 to 0.22; P < 0.001). Foodborne outbreaks in which the vehicle was not
      identified were more frequent in cases of norovirus infection (OR = 4.59; 95% CI,
      2.54 to 8.30; P < 0.001). Our results indicate that norovirus rather than
      Salmonella is the most common cause of AGE outbreaks in Catalonia. Foodborne AGE
      outbreaks were more commonly caused by norovirus than by Salmonella only in 2010,
      the last year of the study. 

PMID- 24112587
TI  - The Role of Chlorhexidine on Endotoxin Penetration to the Implant-Abutment
      Interface (IAI).
AB  - PURPOSE: The aim of this study is to assess the risk of endotoxin penetration to
      the implant-abutment interface (IAI) of implants with Morse-taper connection and
      the effect of chlorhexidine in the prevention of such penetration. MATERIALS AND
      METHODS: Thirty implants with Morse-taper connection were divided into three
      groups (n = 10/group) based on type of inoculation of the internal aspect of the
      implant. Implants in Group 1 were inoculated with 1 MUl Escherichia coli for 24
      hours; supernatant was removed and 0.5 MUl of sterile saline was added. Implants
      in Group 2 were inoculated with 1 MUl E. coli for 24 hours; supernatant was
      removed and 0.5 MUl 0.2% chlorhexidine solution was added. Implants in Group 3
      were inoculated with 0.5 MUl of sterile saline and served as controls. Following
      inoculation procedures, implants were connected to standard abutments, immersed
      in sterile culture media, and loaded with 200,000 cycles of 160 N in a wear
      simulator. Samples were collected from the supernatant solution of each implant
      for endotoxin identification at the beginning of the loading cycle (T0) and
      following 9 hours (T9), 18 hours (T18), 27 hours (T27), 36 hours (T36), 45 hours
      (T45), and 54 hours (T54). RESULTS: For Group 1 and Group 2, there were
      statistically significant differences between the endotoxin concentration at T0
      and the endotoxin concentration at the subsequent sampling points (p < .05
      Kruskal-Wallis with Bonferoni corrections for intragroup comparisons). There were
      no statistically significant differences between Group 1 and Group 2 at all
      sampling points. CONCLUSIONS: This study indicates that bacterial endotoxin can
      penetrate the IAI of implants with Morse-taper connection, and 0.2% chlorhexidine
      solution had no significant effect on that penetration.

PMID- 24112588
TI  - The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic
      dermatitis: a randomized, double-blind, placebo-controlled, crossover study.
AB  - BACKGROUND: Various antihistamines have been used in the management of feline
      atopic dermatitis, with variable reported benefit. To date, there have been no
      randomized, double-blind, placebo-controlled, crossover clinical trials on the
      use of this drug class in cats. HYPOTHESIS/OBJECTIVES: To evaluate the clinical
      efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis
      in cats diagnosed with atopic dermatitis. METHODS: In this randomized, double
      blind, placebo-controlled crossover clinical trial, 21 client-owned cats
      diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly
      assigned to two groups. Cats in each group received either 1 mg/kg cetirizine
      hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash
      out period. Treatments were then crossed over, and cats received placebo or
      cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity
      scale before inclusion in the study and weekly throughout the entire study
      period. Lesions were scored by the clinician using a Canine Atopic Dermatitis
      Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and
      at day 28 of each treatment. RESULTS: Nineteen cats completed the study. There
      were no statistically significant differences between treatment with cetirizine
      hydrochloride and placebo for modified CADESI-03 or pruritus scores. CONCLUSION
      AND CLINICAL IMPORTANCE: This study suggests that cetirizine hydrochloride cannot
      be recommended for the management of feline atopic dermatitis.

PMID- 24112589
TI  - Ecology of leishmaniasis in the South of France. 22. Reliability and
      representativeness of 12 Phlebotomus ariasi, P. perniciosus and Sergentomyia
      minuta (Diptera: Psychodidae) sampling stations in Vallespir (eastern French
      Pyrenees region).
AB  - This study was conducted around Ceret (Pyrenees-Orientales, mean elevation 200 m)
      to test the statistical reliability of 12 stations devoted to sampling the
      Leishmania infantum vectors Phlebotomus ariasi and P. perniciosus in the South of
      France. Each station included a retaining wall and the surrounding
      phytoecological environment (total area: 2,000 m(2)). The wall had rectangular
      drainage cavities (weep holes) in which flight interception traps (sticky paper)
      were inserted and stretched every 10 days from May to October. For both vector
      species, the statistical analysis of 10-day and annual frequencies led to the
      following conclusions: (1) P. ariasi densities were significantly higher than P.
      perniciosus densities, (2) densities per species were significantly different at
      the 12 stations : none of them could be considered as representative of local
      vector densities, which depend on the wall structure (exposure, shade, vertebrate
      hosts), (3) the 10-day variation trends were not significantly different between
      stations, indicating that these variations are not determined by the station
      structure but rather by a common external factor (likely meteorological) and (4)
      the phytoecological features at the stations were not correlated with the sandfly
      densities. Most of the observations obtained with P. ariasi and P. perniciosus
      are also relevant for the non-vectorial species S. minuta. In conclusion, future
      research on the dynamics of leishmaniasis outbreaks relative to climate change
      and agricultural-silvicultural modifications should be very cautiously carried
      out, while focusing especially on the vector sampling quality and the use of
      phytoecological maps as vector density indicators. 

PMID- 24112590
TI  - Development of pure endoscopic full-thickness resection with mechanical
      countertraction and double-armed bar suturing systems.

PMID- 24112591
TI  - Luminal lipoma: the "pot-of-gold" sign.

PMID- 24112592
TI  - In vivo cellular imaging of gastric mucosa-associated lymphoid tissue lymphoma in
      a Helicobacter pylori-negative patient.

PMID- 24112593
TI  - Transnasal PEG tube placement in patients with head and neck cancer.
AB  - BACKGROUND: Head and neck cancer (H&NCa) patients have an increased risk of
      malnutrition and dysphagia because of their malignancy and the adverse events of
      therapy. Most of these patients require gastrostomies. Four percent to 7% of
      H&NCa patients are unable to undergo per oral percutaneous gastrostomies.
      Transnasal endoscopy is an option for gastrostomy placement in selected patients.
      OBJECTIVE: Clinical, epidemiologic characteristics and outcomes of transnasal PEG
      (t-PEG) placement. DESIGN: Retrospective analysis. SETTING: Tertiary care
      hospital, The University of Texas MD Anderson Cancer Center. PATIENTS: All
      patients who underwent t-PEG placement. MAIN OUTCOME MEASUREMENTS: Epidemiology,
      adverse events, and outcomes of t-PEG placement. RESULTS: Sixteen patients
      underwent t-PEG placement from January 2010 to May 2013. All patients had H&NCa
      and 56.3% had metastasis. Indications for the transnasal approach were airway
      compromise, malignant oropharyngeal obstruction, and trismus, among others. All
      procedures were successful using a 20F gastrostomy tube, push technique,
      anesthesiologist-guided propofol sedation, and/or nasotracheal intubation. Of all
      patients, 68.8% were white and 68.8% were men. Mean age was 54 years, and mean
      body mass index was 20.87. Two patients had a total of 2 adverse events: poor
      wound healing and wound site infection. Of all patients, 18.75% had leukopenia,
      6.25% neutropenia, and 50% lymphopenia. Mean white blood cell count, absolute
      neutrophil count, and absolute lymphocyte count were 8.6 * 10(9)/L, 6.57 *
      10(9)/L, and .93 * 10(9)/L, respectively. Eleven patients were alive, 2 were lost
      to follow-up, and 3 had died at the time of review. LIMITATIONS: Retrospective
      analysis, small cohort, patient selection bias. CONCLUSION: t-PEG placement is a
      viable and safe option for H&NCa patients when the standard endoscopic approach
      is not feasible.

PMID- 24112594
TI  - The effect of chewing gum on small-bowel transit time in capsule endoscopy: a
      prospective, randomized trial.
AB  - BACKGROUND: Approximately 1 in 6 capsule endoscopies (CEs) does not visualize the
      entire small bowel at completion of the examination because of limited battery
      life. OBJECTIVE: To determine whether chewing gum can reduce the small-bowel
      transit time and increase CE completion rates. DESIGN: Prospective, single-blind,
      randomized, controlled trial. SETTING: A tertiary university-affiliated hospital.
      PATIENTS: Consecutive patients 19 years of age and older undergoing outpatient
      small-bowel CE from October 2010 to July 2012 were assessed for eligibility.
      Those with previous gastric or small-bowel surgery or ileostomy, dysphagia
      prohibiting capsule ingestion, diabetes mellitus with evidence of end-organ
      damage, use of narcotics or prokinetics within 5 days before the procedure,
      clinical hyper-/hypothyroidism, and symptoms suggestive of acute bowel
      obstruction were excluded. INTERVENTION: Gum chewing for at least 20 minutes
      every 2 hours starting at the time of capsule ingestion. MAIN OUTCOME
      MEASUREMENTS: Small-bowel transit time, gastric transit time, and completion rate
      were measured. RESULTS: Chewing gum did not have any significant effect on
      gastric transit time (rate ratio 1.06; 95% CI, 0.73-1.55; P = .75), small-bowel
      transit time (rate ratio 0.91; 95% CI, 0.62-1.35; P = .65), or completion rate
      (91.67% chewing gum vs 88.71% control, P = .58) of CE. LIMITATION: Single-center
      study involving relatively healthy subjects. Procedures were done on an
      outpatient basis so participants were not monitored for adherence to protocol.
      CONCLUSIONS: Chewing gum does not speed up capsule transit or increase completion
      rate of CE in patients without risk factors for incomplete studies. ( CLINICAL
      TRIAL REGISTRATION NUMBER: NCT01241825.).

PMID- 24112595
TI  - Editorial Comment from Dr Kitamura to Cystectomy and urinary diversion as
      management of treatment-refractory benign disease: the impact of preoperative
      urological conditions on perioperative outcomes.

PMID- 24112596
TI  - In vitro removal of ochratoxin A by two strains of Saccharomyces cerevisiae and
      their performances under fermentative and stressing conditions.
AB  - AIMS: The aim of this research was to study the effect of time, temperature,
      sugar content and addition of diammonium phosphate (DAP) on ochratoxin A (OTA)
      removal by two strains of Saccharomyces cerevisiae using a completely randomized
      design. METHODS AND RESULTS: The strains were grown in a medium containing OTA (2
      MUg l(-1)), two sugar levels (200 and 250 g l(-1)), with or without DAP (300 mg
      l(-1)), and incubated at 25-30 degrees C. The yeasts were able to decrease the
      toxin amount by c. 70%, with the highest removing effect observed after 3 days at
      30 degrees C in the presence of 250 g l(-1) of sugars and with DAP; after 10
      days, the toxin was partially released into the medium. The strains produced high
      ethanol and glycerol contents, showed high tolerance to single/combined stress
      conditions and possessed beta-d-glucosidase, pectinase and xylanase activities.
      CONCLUSIONS: Ochratoxin A removal was affected by time, temperature, sugar and
      addition of DAP. Moreover, the phenomenon was reversible. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Ochratoxin A removal could be an interesting trait for the
      selection of promising strains; however, the strains removing efficiently the
      toxin could release it back; thus, the selection of the starter should take into
      account both the removal and the binding ability of OTA.

PMID- 24112597
TI  - Successful use of sacral neuromodulation in a 12-year-old with cerebral palsy and
      neurogenic bladder.

PMID- 24112598
TI  - In vitro ultrasonic and mechanic characterization of the modulus of elasticity of
      children cortical bone.
AB  - The assessment of elastic properties in children's cortical bone is a major
      challenge for biomechanical engineering community, more widely for health care
      professionals. Even with classical clinical modalities such as X-ray tomography,
      MRI, and/or echography, inappropriate diagnosis can result from the lack of
      reference values for children bone. This study provides values for elastic
      properties of cortical bone in children using ultrasonic and mechanical
      measurements, and compares them with adult values. 18 fibula samples from 8
      children (5-16 years old, mean age 10.6 years old +/-4.4) were compared to 16
      fibula samples from 3 elderly adults (more than 65 years old). First, the dynamic
      modulus of elasticity (Edyn) and Poisson's ratio (nu) are evaluated via an
      ultrasonic method. Second, the static modulus of elasticity (Esta) is estimated
      from a 3-point microbending test. The mean values of longitudinal and transverse
      wave velocities measured at 10 MHz for the children's samples are respectively
      3.2mm/MUs (+/-0.5) and 1.8mm/MUs (+/-0.1); for the elderly adults' samples,
      velocities are respectively 3.5mm/MUs (+/-0.2) and 1.9 mm/MUs (+/-0.09). The mean
      Edyn and the mean Esta for the children's samples are respectively 15.5 GPa (+/
      3.4) and 9.1 GPa (+/-3.5); for the elderly adults' samples, they are respectively
      16.7 GPa (+/-1.9) and 5.8 GPa (+/-2.1). Edyn, nu and Esta are in the same range
      for children's and elderly adults' bone without any parametric statistical
      difference; a ranking correlation between Edyn and Esta is shown for the first
      time.

PMID- 24112599
TI  - Intraosseous monitoring and guiding by ultrasound: a feasibility study.
AB  - An efficient method for navigation within bone tissue boundaries is essential for
      performance of surgical procedures, e.g. without damaging of adjacent vulnerable
      organs. The application of sonographic measuring methods for this purpose
      promises to be effective in the ability to distinguish soft trabecular bone from
      dense cortical bone, owing to an order of magnitude difference in acoustic
      density between these structures. For this purpose, a specific method was
      developed that utilizes propagation of a 5 MHz ultrasonic wave through an aqueous
      milieu. Using this method a 0.2mm resolution in measurements is achieved. This
      resolution is in an order of magnitude lower than is required for a clinical use.
      A three-stage experimental approach was adopted: measurements in a cubic
      "phantom" made of a transparent plastic material, in samples of fresh porcine
      femora, and in a clinical setting of drilling in the upper and lower jaw during
      dental implantation surgery in nine patients. Two patterns of the detected
      ultrasound wave reflections were found: low amplitude reflections from the
      aqueous surrounding and trabecular bone and highly reflected ultrasound waves
      from the cortical bone. We show that trabecular and cortical bones are
      distinguishable by real-time ultrasonic measurement. The distances of the drilled
      tracts, in the range of 58.0-122.0 mm for the "phantom" experiment, 22.6-35.5 mm
      for the ex vivo experiment and 10.0-11.5 mm in the clinical experiment, and
      residual distances to the opposite edge of the tested samples and organs, in the
      range of 21.0-82.0 mm for the "phantom" experiment, 3.8-11.36 mm for the ex vivo
      experiment and 2.1-6.9 mm in the clinical experiment, were measured by the
      presented sonographic method and compared statistically, using linear correlation
      and Bland Altman plot, to the mechanical and/or radiographic measurements in all
      three stages of the experiment. A correlation coefficient above 0.95 was
      considered an indication of high correlation, while a value of 0.75-0.94 was
      considered intermediate, and a value below 0.75 was considered poor. A very high
      correlation (p < 0.001) and agreement between the sonographic and the "gold
      standard" measurements techniques, either mechanical or radiographic depending on
      the experimental setting, were found. Therefore the presented method of
      intraosseous sonographic measurements may provide an improved method for the
      monitoring of intraosseous drilling in respect of the currently used mechanical
      and/or radiographic clinical methods.

PMID- 24112600
TI  - Structure-function studies of Escherichia coli RnlA reveal a novel toxin
      structure involved in bacteriophage resistance.
AB  - Escherichia coli RnlA-RnlB is a newly identified toxin-antitoxin (TA) system that
      plays a role in bacteriophage resistance. RnlA functions as a toxin with mRNA
      endoribonuclease activity and the cognate antitoxin RnlB inhibits RnlA toxicity
      in E. coli cells. Interestingly, T4 phage encodes the antitoxin Dmd, which acts
      against RnlA to promote its own propagation, suggesting that RnlA-Dmd represents
      a novel TA system. Here, we have determined the crystal structure of RnlA refined
      to 2.10  (Dmd-binding domain), which is an organization not previously observed
      among known toxin structures. Small-angle X-ray scattering (SAXS) analysis
      revealed that RnlA forms a dimer in solution via interactions between the DBDs
      from both monomers. The in vitro and in vivo functional studies showed that among
      the three domains, only the DBD is responsible for recognition and inhibition by
      Dmd and subcellular location of RnlA. In particular, the helix located at the C
      terminus of DBD plays a vital role in binding Dmd. Our comprehensive studies
      reveal the key region responsible for RnlA toxicity and provide novel insights
      into its structure-function relationship.

PMID- 24112601
TI  - The effect of ankle bracing on knee kinetics and kinematics during volleyball
      specific tasks.
AB  - The purpose of this study was to examine the effects of ankle bracing on knee
      kinetics and kinematics during volleyball tasks. Fifteen healthy, elite, female
      volleyball players performed a series of straight-line and lateral volleyball
      tasks with no brace and when wearing an ankle brace. A 14-camera Vicon motion
      analysis system and AMTI force plate were used to capture the kinetic and
      kinematic data. Knee range of motion, peak knee anterior-posterior and medial
      lateral shear forces, and peak ground reaction forces that occurred between
      initial contact with the force plate and toe off were compared using paired
      sample t-tests between the braced and non-braced conditions (P < 0.05). The
      results revealed no significant effect of bracing on knee kinematics or ground
      reaction forces during any task or on knee kinetics during the straight-line
      movement volleyball tasks. However, ankle bracing was demonstrated to reduce knee
      lateral shear forces during all of the lateral movement volleyball tasks. Wearing
      the Active Ankle T2 brace will not impact knee joint range of motion and may in
      fact reduce shear loading to the knee joint in volleyball players. 

PMID- 24112602
TI  - Using patient-reported outcomes to assess and improve prostate cancer
      brachytherapy.
AB  - OBJECTIVE: To describe a successful quality improvement process that arose from
      unexpected differences in control groups' short-term patient-reported outcomes
      (PROs) within a comparative effectiveness study of a prostate brachytherapy
      technique intended to reduce urinary morbidity. PATIENTS AND METHODS: Patients
      planning prostate brachytherapy at one of three institutions were enrolled in a
      prospective cohort study. Patients were surveyed using a validated instrument to
      assess treatment-related toxicity before treatment and at pre-specified
      intervals. Unexpectedly, urinary PROs were worse in one of two standard
      brachytherapy technique control populations (US-BT1 and US-BT2 ). Therefore, we
      collaboratively reviewed treatment procedures, identified a discrepancy in
      technique, made a corrective modification, and evaluated the change. RESULTS: The
      patient groups were demographically and clinically similar. In the first
      preliminary analysis, US-BT2 patients reported significantly more short-term post
      treatment urinary symptoms than US-BT1 patients. The study's treating physicians
      reviewed the US-BT1 and US-BT2 treatment protocols and found that they differed
      in whether they used an indwelling urinary catheter. After adopting the US-BT1
      approach, short-term urinary morbidity in US-BT2 patients decreased
      significantly. Brachytherapy procedures were otherwise unchanged. CONCLUSION:
      Many procedures in cancer treatments are not evaluated, resulting in practice
      variation and suboptimal outcomes. Patients, the primary medical consumers,
      provide little direct input in evaluations of their care. We used PROs, a
      sensitive and valid measure of treatment-related toxicity, for quality assessment
      and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous
      patient-centred QA/QI process may be a useful model for empirically evaluating
      complex cancer treatment procedures and for screening for substandard care.

PMID- 24112603
TI  - Seedling development in buckwheat and the discovery of the photomorphogenic shade
      avoidance response.
AB  - Numerous botanists of the early 19th century investigated the effect of sunlight
      on plant development, but no clear picture developed. One hundred and fifty years
      ago, Julius Sachs (1863) systematically analysed the light-plant relationships,
      using developing garden nasturtium (Tropaeolum majus) and seedlings of buckwheat
      (Fagopyron esculentum) as experimental material. From these studies, Sachs
      elucidated the phenomenon of photomorphogenesis (plant development under the
      influence of daylight) and the associated 'shade-avoidance response'. We have
      reproduced the classical buckwheat experiments of Sachs (1863) and document the
      original shade-avoidance syndrome with reference to hypocotyl elongation and
      cotyledon development in darkness (skotomorphogenesis), white light and shade
      induced by a canopy of green leaves. In subsequent publications, Sachs elaborated
      his concepts of 1863 and postulated the occurrence of 'flower-inducing
      substances'. In addition, he argued that the shade-avoidance response in cereals,
      such as wheat and maize, is responsible for lodging in crowded plant communities.
      We discuss these processes with respect to the red- to far-red light/phytochrome
      B relationships. Finally, we summarise the phytochrome B-phytohormone (auxin,
      brassinosteroids) connection within the cells of shaded Arabidopsis plants, and
      present a simple model to illustrate the shade-avoidance syndrome. In addition,
      we address the relationship between plant density and health of the corresponding
      population, a topic that was raised for the first time by Sachs (1863) in his
      seminal paper and elaborated in his textbooks. 

PMID- 24112604
TI  - Histoplasma yeast and mycelial transcriptomes reveal pathogenic-phase and lineage
      specific gene expression profiles.
AB  - BACKGROUND: The dimorphic fungus Histoplasma capsulatum causes respiratory and
      systemic disease in mammalian hosts by expression of factors that enable survival
      within phagocytic cells of the immune system. Histoplasma's dimorphism is
      distinguished by growth either as avirulent mycelia or as pathogenic yeast.
      Geographically distinct strains of Histoplasma differ in their relative virulence
      in mammalian hosts and in production of and requirement for specific virulence
      factors. The close similarity in the genome sequences of these diverse strains
      suggests that phenotypic variations result from differences in gene expression
      rather than gene content. To provide insight into how the transcriptional program
      translates into morphological variation and the pathogenic lifestyle, we compared
      the transcriptional profile of the pathogenic yeast phase and the non-pathogenic
      mycelial phase of two clinical isolates of Histoplasma. RESULTS: To overcome
      inaccuracies in ab initio genome annotation of the Histoplasma genome, we used
      RNA-seq methodology to generate gene structure models based on experimental
      evidence. Quantitative analyses of the sequencing reads revealed 6% to 9% of
      genes are differentially regulated between the two phases. RNA-seq-based mRNA
      quantitation was strongly correlated with gene expression levels determined by
      quantitative RT-PCR. Comparison of the yeast-phase transcriptomes between strains
      showed 7.6% of all genes have lineage-specific expression differences including
      genes contributing, or potentially related, to pathogenesis. GFP-transcriptional
      fusions and their introduction into both strain backgrounds revealed that the
      difference in transcriptional activity of individual genes reflects both
      variations in the cis- and trans-acting factors between Histoplasma strains.
      CONCLUSIONS: Comparison of the yeast and mycelial transcriptomes highlights genes
      encoding virulence factors as well as those involved in protein glycosylation,
      alternative metabolism, lipid remodeling, and cell wall glycanases that may
      contribute to Histoplasma pathogenesis. These studies lay an essential foundation
      for understanding how gene expression variations contribute to the strain- and
      phase-specific virulence differences of Histoplasma.

PMID- 24112605
TI  - Radiation testing of the AeroForm CO2-based breast tissue expander implant.
AB  - BACKGROUND: Tissue expanders are used in breast reconstruction after mastectomy
      to stretch the remaining tissue to create space for placement of permanent breast
      implants. The AeroFormTM Tissue Expander, developed by AirXpandersTM Inc.,
      contains electronic components designed to activate the release of carbon dioxide
      from an internal reservoir to inflate the expander. Breast cancer patients who
      undergo mastectomy and tissue expander/implant-based breast reconstruction may
      require radiation therapy at doses up to 50-60 Gy while the expander is in place.
      The ionizing radiation used in postmastectomy radiation therapy interacts with
      electronic components in medical implants, which may cause degradation in
      performance above certain levels. Most commercial electronic components used in
      medical devices, such as complementary metal-oxide semiconductor or bipolar
      integrated circuits can withstand radiation levels in the 50 Gy range without any
      performance degradation. Beyond this level, the performance may still be
      sufficient to guarantee functionality, but this needs to be confirmed at the
      system and electronic circuit level. We assessed the impact of radiation levels
      up to 75 Gy on 32 AeroFormTM Tissue Expanders (AirXpanders, Inc., Palo Alto, CA
      USA) and on the associated internal printed circuit assemblies. FINDINGS: The
      electronics inside the AeroFormTM Tissue Expander implant continued to function
      properly after exposure to radiation levels up to 75 Gy, which is well above the
      maximum total dose level typically used in postmastectomy radiation therapy.
      CONCLUSIONS: Standard postmastectomy radiation therapy doses do not damage or
      affect the functionality of the AeroFormTM Tissue Expander.

PMID- 24112606
TI  - miRNA expression is modulated over time after focal ischaemia: up-regulation of
      miR-347 promotes neuronal apoptosis.
AB  - Despite the large number of molecules reported as being over-expressed after
      ischaemia, little is known regarding their regulation. miRNAs are potent post
      transcriptional regulators of gene expression, and reports have shown
      differentially miRNA expression in response to focal cerebral ischaemia. The
      present study analysed miRNA expression from acute to late phases of ischaemia to
      identify specific ischaemia-related miRNAs, elucidate their role, and identify
      potential targets involved in stroke pathophysiology. Of 112 miRNAs, 32 showed
      significant changes and different expression profiles. In addition to the
      previously reported differentially expressed miRNAs, new ischaemia-regulated
      miRNAs have been found, including miR-347. Forty-seven genes involved in brain
      functions or related to ischaemia are predicted to be potential targets of the
      differentially expressed miRNAs after middle cerebral artery occlusion. Analysis
      of four of these targets (Acsl4, Arf3, Btg2 and Dpysl5) showed them to be
      differentially regulated by ischaemia at the transcriptional or post
      transcriptional level. Acsl4, Bnip3l and Phyhip, potential targets of miR-347,
      were up-regulated after miR-347 over-expression, inducing neuronal apoptotic
      death. Our findings suggest that miR-347 plays an important role in regulating
      neuronal cell death, identify Acsl4 as a new protein requiring study in
      ischaemia, and provide an important resource for future functional studies of
      miRNAs after ischaemia. 

PMID- 24112607
TI  - MiRNA-497 regulates cell growth and invasion by targeting cyclin E1 in breast
      cancer.
AB  - BACKGROUND: MicroRNAs are a class of endogenous single strand non-coding RNAs
      that are involved in many important physiological and pathological processes. The
      purpose of this study was to examine the expression levels of miR-497 in human
      breast cancer and its function in MDA-MB-231 breast cancer cells. METHODS:
      Quantitative polymerase chain reaction was used to measure the expression levels
      of miR-497 in 40 breast cancer specimens and adjacent normal breast tissues. MTT
      assays, colony formation assays, wound healing assays, transwell assays and cell
      cycle assays were used to explore the potential function of miR-497 in MDA-MB-231
      breast cancer cells. Dual-luciferase reporter assays were performed to analyze
      the regulation of putative target of miR-497, and western blot assays were used
      to validate the dual-luciferase results. RESULTS: The expression of miR-497 in
      breast cancer specimens was lower than adjacent normal tissues (P < 0.05).
      Overexpression of miR-497 inhibited cellular growth, suppressed cellular
      migration and invasion, and caused a G1 arrest. Dual-luciferase reporter assays
      showed that miR-497 binds the 3'-untranslated region (3'-UTR) of cyclin E1,
      suggesting that cyclin E1 is a direct target of miR-497. Western blot assays
      confirmed that overexpression of miR-497 reduced cyclin E1 protein levels.
      CONCLUSIONS: MiR-497 may act as a tumor suppressor gene in breast cancer.
      Inhibited cellular growth, suppressed cellular migration and invasion, and G1
      cell cycle arrest were observed upon overexpression of miR-497 in cells, possibly
      by targeting cyclin E1. These results indicate miR-497 could be considered a
      therapeutic target for the development of treatment for breast cancer.

PMID- 24112608
TI  - Prognostic significance and therapeutic potential of the activation of anaplastic
      lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway
      in anaplastic large cell lymphoma.
AB  - BACKGROUND: Activation of the protein kinase B/mammalian target of rapamycin
      (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin
      anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large
      cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of
      other cancers. However, the prognostic value of AKT/mTOR activation in ALCL
      remains to be fully elucidated. In the present study, we aim to address this
      question from a clinical perspective by comparing the expressions of the AKT/mTOR
      signaling molecules in ALCL patients and exploring the therapeutic significance
      of targeting the AKT/mTOR pathway in ALCL. METHODS: A cohort of 103 patients with
      ALCL was enrolled in the study. Expression of ALK fusion proteins and the
      AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC)
      staining. The pathogenic role of ALK fusion proteins and the therapeutic
      significance of targeting the ATK/mTOR signaling pathway were further
      investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK
      transformed BaF3 cells. RESULTS: ALK expression was detected in 60% of ALCLs, of
      which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed
      variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1),
      and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in
      76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT)
      and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated
      to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not
      correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred
      more commonly in younger patients, and ALK + ALCL patients had a much better
      prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or
      p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM
      ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the cells to
      become cytokine-independent and resistant to glucocorticoids (GCs). Targeting
      AKT/mTOR inhibited growth and triggered the apoptotic cell death of ALK + ALCL
      cells and NPM-ALK transformed BaF3 cells, and also reversed GC resistance induced
      by overexpression of NPM-ALK. CONCLUSIONS: Overexpression of ALK due to
      chromosomal translocations is seen in the majority of ALCL patients and endows
      them with a much better prognosis. The AKT/mTOR signaling pathway is highly
      activated in ALK + ALCL patients and targeting the AKT/mTOR signaling pathway
      might confer a great therapeutic potential in ALCL.

PMID- 24112609
TI  - Pulpal response to sensibility tests after traumatic dental injuries in permanent
      teeth.
AB  - BACKGROUND/AIM: The assessment of pulp vitality is one of the major challenges in
      dental traumatology due to the temporary loss of sensibility after trauma and
      because of the limitations of conventional pulp tests. The aim of this study was
      to evaluate pulpal response to sensibility tests and to determine their accuracy
      after crown fractures and luxation injuries. MATERIALS AND METHODS: A total of
      121 permanent anterior teeth from 78 patients treated at the Dental Trauma Clinic
      of the Federal University of Minas Gerais were evaluated. Responses to pulp
      sensibility tests were monitored for a minimum period of 24 months or until the
      diagnosis of pulp necrosis. RESULTS: At the first appointment, 68 teeth responded
      positively to sensibility tests, one tooth was necrotic and 52 teeth did not
      respond to sensibility tests but showed no other signs of necrosis. The initial
      lack of response was not associated with age (P = 0.18), but was related to the
      presence of luxation (P < 0.001). At the final appointment, 87 teeth were
      classified as vital and 31 were classified as non-vital. While a positive
      response shortly after trauma was a good predictor of vitality, a lack of
      response was not associated with subsequent necrosis. The final pulpal condition
      of the teeth that initially did not respond was associated with the type of
      injury, as displaced teeth tended to develop necrosis (P = 0.008). The accuracy
      of each sensibility test at the initial and final appointments was, respectively,
      55.1% and 67.8% for the heat test, 55.9% and 77.9% for the cold test, and 57.6%
      and 89% for the electrical test. CONCLUSIONS: A temporary loss of sensibility was
      a frequent finding during post-traumatic pulpal healing, especially after
      luxation injuries. All sensibility tests presented low accuracy shortly after
      trauma. The electrical test provided the best support for pulpal diagnosis after
      long-term follow up. The clinician must be aware of additional signs of crown
      discoloration and radiographic changes before initiating endodontic treatment.

PMID- 24112610
TI  - Genetic assignment of recruits reveals short- and long-distance larval dispersal
      in Pocillopora damicornis on the Great Barrier Reef.
AB  - Understanding connectivity of coral populations among and within reefs over
      ecologically significant timescales is essential for developing evidence-based
      management strategies, including the design of marineprotected areas. Here, we
      present the first assessment of contemporary connectivity among populations of
      two Molecular Operational Taxonomic Units (MOTUs) of the brooding coral
      Pocillopora damicornis. We used individual-based genetic assignment methods to
      identify the proportions of philopatric and migrant larval recruits, settling
      over 12 months at sites around Lizard Island (northern Great Barrier Reef [GBR])
      and over 24 months at sites around the Palms Islands (central GBR). Overall, we
      found spatially and temporally variable rates of self-recruitment and dispersal,
      demonstrating the importance of variation in local physical characteristics in
      driving dispersal processes. Recruitment patterns and inferred dispersal
      distances differed between the two P. damicornis MOTUs, with type alpha recruits
      exhibiting predominantly philopatric recruitment, while the majority of type beta
      recruits were either migrants from identified putative source populations or
      assumed migrants based on genetic exclusion from all known populations. While P.
      damicornis invests much energy into brooding clonal larvae, we found that only
      15% and 7% of type alpha and type beta recruits, respectively, were clones of
      sampled adult colonies or other recruits, challenging the hypothesis that
      reproduction is predominantly asexual in this species on the GBR. We explain high
      rates of self-recruitment and low rates of clonality in these MOTUs by suggesting
      that locally retained larvae originate predominantly from spawned gametes, while
      brooded larvae are mainly vagabonds. 

PMID- 24112611
TI  - Oligomerization is a key step in Cyt1Aa membrane insertion and toxicity but not
      necessary to synergize Cry11Aa toxicity in Aedes aegypti larvae.
AB  - Bacillus thuringiensis produces insecticidal Cry and Cyt proteins that are toxic
      to different insect orders. In addition, Cyt toxins also display haemolytic
      activity. Both toxins are pore-forming proteins that form oligomeric structures
      that insert into the target membrane to lyse cells. Cyt toxins play an important
      role in mosquitocidal activity since they synergize Cry toxins and are able to
      overcome resistance to Cry toxins. Cry and Cyt toxins interact by specific
      epitopes, and this interaction is important to induce the synergistic activity
      observed. It was proposed that Cyt toxins do not interact with protein receptors
      but directly interacting with the specific midgut cell lipids. Here, we analysed
      if oligomerization and membrane insertion of Cyt1Aa are necessary steps to
      synergize Cry11Aa toxicity. We characterized Cyt1Aa helix alpha-C mutants that
      were affected in oligomerization, in membrane insertion and also in haemolytic
      and insecticidal activities. However, these mutants were still able to synergize
      Cry11Aa toxicity indicating these steps are independent events of Cyt1Aa
      synergistic activity. Furthermore, the data indicate that formation of stable
      Cyt1Aa-oligomeric structure is a key step for membrane insertion, haemolysis and
      insecticidal activity. 

PMID- 24112612
TI  - Words of wisdom. Re: Active surveillance for prostate cancer compared with
      immediate treatment: an economic analysis.

PMID- 24112613
TI  - Words of wisdom. Re: Low serum neutrophil count predicts a positive prostate
      biopsy.

PMID- 24112614
TI  - Words of wisdom. Re: Early detection of prostate cancer: AUA guideline.

PMID- 24112615
TI  - Words of wisdom. Re: African American men with very low-risk prostate cancer
      exhibit adverse oncologic outcomes after radical prostatectomy: should active
      surveillance still be an option for them?

PMID- 24112616
TI  - Words of wisdom. Re: Role of immunohistochemistry in the evaluation of needle
      core biopsies in adult renal cortical tumors: an ex vivo study.

PMID- 24112617
TI  - Words of wisdom. Re: Increased pregnancy after reduced male abstinence.

PMID- 24112619
TI  - Methicillin-resistant Staphylococcus aureus screening as a patient safety
      initiative: using patients' experiences to improve the quality of screening
      practices.
AB  - AIMS AND OBJECTIVES: To explore the patient experience and acceptability of
      methicillin-resistant Staphylococcus aureus screening of inpatient admissions to
      acute hospital settings. BACKGROUND: Prevention of healthcare-associated
      infections such as methicillin-resistant Staphylococcus aureus is a major patient
      safety concern internationally. Screening of patients for methicillin-resistant
      Staphylococcus aureus colonisation is becoming a routine aspect of hospital
      admission; however, evidence of the patient experience and acceptability of
      methicillin-resistant Staphylococcus aureus screening is limited. DESIGN: A mixed
      methods study set in six acute care hospitals in three Scottish regions. METHODS:
      Data collection involved postdischarge self-report survey of patients who had
      been screened (n = 54) and qualitative patient interviews (n = 10). Theoretical
      constructs derived from the Health Belief Model and Theory of Planned Behaviour
      used in analysis. RESULTS: Findings indicated that methicillin-resistant
      Staphylococcus aureus screening was broadly acceptable to patients. The
      experience of screening did not appear to be problematic; responses demonstrate
      that screening provided reassurance and generated confidence that health
      organisations were tackling healthcare-associated infections. Patients were less
      positive regarding the provision of information, the possibility of refusing a
      screen and the consequences of a positive test result. Furthermore, there were
      indications that patients wanted to be told the results of the screen and strong
      support for screening of hospital staff. CONCLUSIONS: Analysis of constructs from
      our theoretical frameworks provides evidence that attitudes were largely
      positive; responses indicate a belief in the beneficial impact of methicillin
      resistant Staphylococcus aureus screening for patients and the wider community.
      However, it is important that health professionals continually assess the patient
      experience of 'routine' aspects of health care such as MRSA screening. RELEVANCE
      TO CLINICAL PRACTICE: The findings from this study suggest that while methicillin
      resistant Staphylococcus aureus screening is generally acceptable to patients as
      a regular patient safety initiative, to enhance the quality of the patient
      experience, clinicians should consider the timing, content and effectiveness of
      information provision.

PMID- 24112618
TI  - Genetic architecture of retinal and macular degenerative diseases: the promise
      and challenges of next-generation sequencing.
AB  - Inherited retinal degenerative diseases (RDDs) display wide variation in their
      mode of inheritance, underlying genetic defects, age of onset, and phenotypic
      severity. Molecular mechanisms have not been delineated for many retinal
      diseases, and treatment options are limited. In most instances, genotype
      phenotype correlations have not been elucidated because of extensive clinical and
      genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome,
      genome, transcriptome and epigenome sequencing, provide novel avenues towards
      achieving comprehensive understanding of the genetic architecture of RDDs. Whole
      exome sequencing (WES) has already revealed several new RDD genes, whereas RNA
      Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene
      regulation and biological networks that are involved in retinal development,
      aging and disease. In this review, we focus on the genetic characterization of
      retinal and macular degeneration using NGS technology and discuss the basic
      framework for further investigations. We also examine the challenges of NGS
      application in clinical diagnosis and management. 

PMID- 24112620
TI  - Adaptive changes in geranylgeranyl pyrophosphate synthase gene expression level
      under ethanol stress conditions in Oenococcus oeni.
AB  - AIMS: The aim of this study was to investigate the effect of ethanol exposure on
      the expression level of geranylgeranyl pyrophosphate synthase gene involved in
      the metabolism of Oenococcus oeni to probe the mechanisms of ethanol tolerance
      correlated with adaptive changes. METHODS AND RESULTS: The evaluation of ten
      potential internal control genes and the comparative study of their stability
      were performed to select the most stable internal controls for the normalization
      of expression data. The expression level analysis by qPCR and changes after
      exposure to ethanol stresses highlighted a significant increase in the presence
      of higher ethanol concentrations. CONCLUSIONS: The analysis of results suggest
      that O. oeni adjusts the expression of genes to adapt to stress conditions and
      the high expression level of ggpps would allow a flow of isoprenoid precursors
      towards the carotenoids and related pathways to stabilize bacterial cell
      membranes, improving the cell membrane disturbances and preventing cell death
      induced by ethanol. SIGNIFICANCE AND IMPACT OF THE STUDY: The involvement of
      ggpps gene in physiological changes of bacterial behaviour confirmed the exposure
      to stress requires the activation of defence mechanism to be more tolerant to
      adverse conditions. Improving the knowledge of stress tolerance and adaptation
      mechanisms of O. oeni is essential to enhance the efficiency of the malolactic
      starter in wine and to obtain the development of starters able to survive to
      direct inoculation with a large benefit for wine technology.

PMID- 24112621
TI  - Dimethylfumarate induces apoptosis in human mast cells.
AB  - Mast cells modulate autoimmune diseases such as psoriasis and multiple sclerosis.
      Fumaric acid esters (FAEs) are widely used for the treatment of psoriasis, and
      dimethylfumarate (DMF) has recently been approved for multiple sclerosis. In this
      study, we analysed the cytotoxic effect of FAEs on human mast cells.
      Specifically, cell death was analysed in the human mast cell line HMC-1 and in
      primary cord blood-derived mast cells (CBMCs) after incubation with fumaric acid
      (FA), monomethylfumarate (MMF), DMF and calcium bis(monomethylfumarate) (Ca-MF).
      Our data show that only DMF potently induces apoptotic cell death in HMC-1 cells
      and CBMCs. DMF-mediated apoptosis was associated with increased expression of Bax
      and Bak and activation of caspase-9 and caspase-6. Interestingly, DMF also
      enhanced the sensitivity of CBMCs towards TRAIL- and dexamethasone-induced
      apoptosis. These findings demonstrate for the first time that DMF induces
      apoptosis of human mast cells, primarily via the mitochondrial apoptotic pathway.
      Our study contributes to the understanding of the beneficial effects of FAEs in
      autoimmune diseases and provides a rationale for exploiting FAEs for other
      diseases associated with mast cells. 

PMID- 24112622
TI  - Blockade of dopamine D1-like receptor signalling protects mice against OVA
      induced acute asthma by inhibiting B-cell activating transcription factor
      signalling and Th17 function.
AB  - Previous studies have consistently demonstrated that dopamine D1-like receptor
      (D1-like-R) signalling is implicated in the pathogenesis of experimental
      autoimmune encephalomyelitis and type I diabetes. Given that allergic asthma
      shares certain disease aetiology similarities with autoimmune diseases, we
      conducted studies in OVA-induced mice aiming to address the impact of D1-like-R
      signalling on the pathogenesis of allergic asthma. It was noted that blockade of
      D1-like-R signalling provided protection for mice against OVA-induced acute
      asthma. Particularly, treatment of OVA-induced mice with SCH23390, a D1-like-R
      antagonist, significantly attenuated inflammatory infiltration in the airways
      along with repressed goblet cell hyperplasia and mucus production, as well as
      airway resistance. By contrast, administration of SKF83959, a D1-like-R agonist,
      displayed the opposite effect. Blockade of D1-like-R signalling impaired Th17
      function, as manifested by a significant reduction of Th17 cells in the spleen
      and bronchoalveolar lavage fluid. Mechanistic studies revealed that D1-like-R
      signalling enhances B-cell activating transcription factor activity, which then
      transcribes the expression of RORgammat, a Th17 transcription factor;
      accordingly, D1-like-R signalling regulates Th17 differentiation to promote the
      development of allergic asthma. Taken together, the data obtained in the present
      suggest that blockade of D1-like-R signalling could be an effective therapeutic
      strategy for the prevention and treatment of allergic asthma in clinical
      practice. 

PMID- 24112623
TI  - Progression and predictors of physical activity levels after radical
      prostatectomy.
AB  - OBJECTIVE: To investigate the progression of all aspects (total, occupational,
      sports, household) of physical activity (PA) over time after radical
      prostatectomy (RP) and to find predictive factors for a decrease in PA. PATIENTS
      AND METHODS: In all, 240 men planned for open or robot-assisted RP were analysed.
      All patients completed the Flemish Physical Activity Computerised Questionnaire
      before RP concerning PA over the past year and at 6 weeks, 3, 6 and 12 months
      after RP for the PA of the past month. A linear model for repeated measures was
      used to evaluate the progression of continuous variables over time and the effect
      of various predictors for the progression of patients over time. A logistic
      regression model for repeated measures was used to evaluate binary measures.
      RESULTS: Total, occupational, sports and household PA levels were significantly
      decreased at 6 weeks after RP, but recovered quickly to approximately baseline
      levels from that time. Predictive factors for decreased PA levels at 6 weeks
      after RP were a younger age (total PA level), being unskilled/semi-skilled
      (occupational PA level) and being unemployed/retired (household PA level). RP
      type (open vs robot-assisted) did not influence the different PA levels at 6
      weeks, 3, 6 or 12 months after RP. The severity of first day incontinence and
      urine loss measured at 6 weeks and 3, 6 and 12 months after RP significantly
      affected total and/or household PA level at all time-points. CONCLUSIONS: This is
      the first study to investigate the progression of all aspects of PA (total,
      occupational, sports and household) after RP and to find predictive factors for a
      decrease in PA. All PA levels were significantly decreased at 6 weeks after RP
      and recovered quickly to approximately baseline levels from that time. Patients
      that had robot-assisted RP did not have a faster recovery of PA than those that
      had open RP. Severity of first day incontinence and urine loss measured at 6
      weeks and 3, 6 and 12 months after RP were significantly related to total and/or
      household PA level at all time-points.

PMID- 24112624
TI  - Soft and Hard Tissue Response to Zirconia versus Titanium One-Piece Implants
      Placed in Alveolar and Palatal Sites: A Randomized Control Trial.
AB  - BACKGROUND: Titanium (Ti) implants have been used in the last four decades to
      replace missing teeth. Alternatives to Ti such as zirconia (Zr) may offer
      aesthetic advantages and be more acceptable to patients and clinicians concerned
      about Ti allergy but must show equivalent biological acceptability to Ti.
      PURPOSE: The research aimed to investigate soft and hard tissue response to Ti
      and Zr implants in edentulous patients. MATERIALS AND METHODS: The research
      included 24 participants (Ti = 12, Zr = 12) restored with one-piece ball-abutment
      implants to support overdentures. Participants received four maxillary implants
      (two in the premolar alveolus, one off center in the alveolar midline, and one
      wide-diameter implant in the anterior median palate) and three mandibular
      implants (one in the midline and bilateral posterior implants). RESULTS: Success
      rates for both Ti and Zr implants were low, 67.9% for all alveolar implants and a
      survival rate of 50.0% for the palatal implants. Only 11 (52.4%) of 21 palatal
      implants survived the follow-up period. Peri-implant health was equivalent for Ti
      and Zr implants and showed no statistically significant changes from loading to
      the 1-year follow-up. Statistically significant differences were noted in
      radiographic bone level between Ti and Zr implants (p = .02), with Zr showing
      greater bone loss. CONCLUSIONS: Although the failure rates with the one-piece Zr
      implants were higher than with the Ti ones, suggesting that the former's clinical
      usage as in this study cannot be recommended, it should be borne in mind that the
      fault may also lie with the novel prosthodontic design which was used.

PMID- 24112625
TI  - Microbial pesticide removal in rapid sand filters for drinking water treatment-
      potential and kinetics.
AB  - Filter sand samples, taken from aerobic rapid sand filters used for treating
      groundwater at three Danish waterworks, were investigated for their pesticide
      removal potential and to assess the kinetics of the removal process. Microcosms
      were set up with filter sand, treated water, and the pesticides or metabolites
      mecoprop (MCPP), bentazone, glyphosate and p-nitrophenol were applied in initial
      concentrations of 0.03-2.4 MUg/L. In all the investigated waterworks the
      concentration of pesticides in the water decreased - MCPP decreased to 42-85%,
      bentazone to 15-35%, glyphosate to 7-14% and p-nitrophenol 1-3% - from the
      initial concentration over a period of 6-13 days. Mineralisation of three out of
      four investigated pesticides was observed at Sjaelso waterworks Plant II - up to
      43% of the initial glyphosate was mineralised within six days. At Sjaelso
      waterworks Plant II the removal kinetics of bentazone revealed that less than 30
      min was needed to remove 50% of the bentazone at all the tested initial
      concentrations (0.1-2.4 MUg/L). Increased oxygen availability led to greater and
      faster removal of bentazone in the microcosms. After 1 h, bentazone removal (an
      initial bentazone concentration of 0.1 MUg/L) increased from 0.21%/g filter sand
      to 0.75%/g filter sand, when oxygen availability was increased from 0.28 mg O2/g
      filter sand to 1.09 mg O2/g filter sand. Bentazone was initially cleaved in the
      removal process. A metabolite, which contained the carbonyl group, was removed
      rapidly from the water phase and slowly mineralised after 24 h, while a
      metabolite which contained the benzene-ring was still present in the water phase.
      However, the microbial removal of this metabolite was initiated over seven days.

PMID- 24112626
TI  - Bioaccumulation of human waterborne protozoa by zebra mussel (Dreissena
      polymorpha): interest for water biomonitoring.
AB  - Cryptosporidium parvum, Giardia duodenalis and Toxoplasma gondii are ubiquitous
      pathogens, which waterborne transmission has been largely demonstrated. Since
      they can be found in various watercourses, interactions with aquatic organisms
      are possible. Protozoan detection for watercourses biomonitoring is currently
      based on large water filtration. The zebra mussel, Dreissena polymorpha, is a
      choice biological model in ecotoxicological studies which are already in use to
      detect chemical contaminations in watercourses. In the present study, the zebra
      mussel was tested as a new tool for detecting water contamination by protozoa. In
      vivo exposures were conducted in laboratory experiments. Zebra mussel was exposed
      to various protozoan concentrations for one week. Detection of protozoa was
      realized by Taqman real time qPCR. Our experiments evidenced C. parvum, G.
      duodenalis and T. gondii oocyst bioaccumulation by mussels proportionally to
      ambient contamination, and significant T. gondii prevalence was observed in
      muscle tissue. To our knowledge, this is the first study that demonstrates T.
      gondii oocyst accumulation by zebra mussel. The results from this study highlight
      the capacity of zebra mussels to reveal ambient biological contamination, and
      thus to be used as a new effective tool in sanitary biomonitoring of water
      bodies.

PMID- 24112627
TI  - A novel magnetic Fe@Au core-shell nanoparticles anchored graphene oxide
      recyclable nanocatalyst for the reduction of nitrophenol compounds.
AB  - In this study, a novel catalyst based on Fe@Au bimetallic nanoparticles involved
      graphene oxide was prepared and characterized by transmission electron microscope
      (TEM), and x-ray photoelectron spectroscopy (XPS). The nanomaterial was used in
      catalytic reductions of 4-nitrophenol and 2-nitrophenol in the presence of sodium
      borohydride. The experimental parameters such as temperature, the dosage of
      catalyst and the concentration of sodium borohydride were studied. The rates of
      catalytic reduction of the nitrophenol compounds have been found as the sequence:
      4-nitrophenol>2-nitrophenol. The kinetic and thermodynamic parameters of
      nitrophenol compounds were determined. Activation energies were found as 2.33
      kcal mol(-1) and 3.16 kcal mol(-1) for 4-nitrophenol and 2-nitrophenol,
      respectively. The nanomaterial was separated from the product by using a magnet
      and recycled after the reduction of nitrophenol compounds. The recyclable of the
      nanocatalyst is economically significant in industry.

PMID- 24112628
TI  - Impact of nano zero valent iron (NZVI) on methanogenic activity and population
      dynamics in anaerobic digestion.
AB  - Nano zero valent iron (NZVI), although being increasingly used for environmental
      remediation, has potential negative impact on methanogenesis in anaerobic
      digestion. In this study, NZVI (average size = 55 +/- 11 nm) showed inhibition of
      methanogenesis due to its disruption of cell integrity. The inhibition was
      coincident with the fast hydrogen production and accumulation due to NZVI
      dissolution under anaerobic conditions. At the concentrations of 1 mM and above,
      NZVI reduced methane production by more than 20%. At the concentration of 30 mM,
      NZVI led to a significant increase in soluble COD (an indication of cell
      disruption) and volatile fatty acids in the mixed liquor along with an
      accumulation of H2, resulting in a reduction of methane production by 69% (+/-4%
      [standard deviation]). By adding a specific methanogenesis inhibitor-sodium 2
      bromoethanesulfonate (BES) to the anaerobic sludge containing 30 mM NZVI, the
      amount of H2 produced was only 79% (+/-1%) of that with heat-killed sludge,
      indicating the occurrence of bacterially controlled hydrogen utilization
      processes. Quantitative PCR data was in accordance with the result of
      methanogenesis inhibition, as the level of methanogenic population (dominated by
      Methanosaeta) in the presence of 30 mM NZVI decreased significantly compared to
      that of the control. On the contrary, ZVI powder (average size <212 MUm) at the
      same concentration (30 mM) increased methane production presumably due to
      hydrogenotrophic methanogenesis of hydrogen gas that was slowly released from the
      NZVI powder. While it is a known fact that NZVI disrupts cell membranes, which
      inhibited methanogenesis described herein, the results suggest that the rapid
      hydrogen production due to NZVI dissolution also contribute to methanogenesis
      inhibition and lead to bacterially controlled hydrogenotrophic processes.

PMID- 24112629
TI  - Sewer deterioration modeling with condition data lacking historical records.
AB  - Accurate predictions of future conditions of sewer systems are needed for
      efficient rehabilitation planning. For this purpose, a range of sewer
      deterioration models has been proposed which can be improved by calibration with
      observed sewer condition data. However, if datasets lack historical records,
      calibration requires a combination of deterioration and sewer rehabilitation
      models, as the current state of the sewer network reflects the combined effect of
      both processes. Otherwise, physical sewer lifespans are overestimated as pipes in
      poor condition that were rehabilitated are no longer represented in the dataset.
      We therefore propose the combination of a sewer deterioration model with a simple
      rehabilitation model which can be calibrated with datasets lacking historical
      information. We use Bayesian inference for parameter estimation due to the
      limited information content of the data and limited identifiability of the model
      parameters. A sensitivity analysis gives an insight into the model's robustness
      against the uncertainty of the prior. The analysis reveals that the model results
      are principally sensitive to the means of the priors of specific model
      parameters, which should therefore be elicited with care. The importance sampling
      technique applied for the sensitivity analysis permitted efficient implementation
      for regional sensitivity analysis with reasonable computational outlay.
      Application of the combined model with both simulated and real data shows that it
      effectively compensates for the bias induced by a lack of historical data. Thus,
      the novel approach makes it possible to calibrate sewer pipe deterioration models
      even when historical condition records are lacking. Since at least some prior
      knowledge of the model parameters is available, the strength of Bayesian
      inference is particularly evident in the case of small datasets. 

PMID- 24112630
TI  - Rechargeable deep brain stimulation implantable pulse generators in movement
      disorders: patient satisfaction and conversion parameters.
AB  - OBJECTIVES: Rechargeable (RC) implantable pulse generators (IPGs) for deep brain
      stimulation (DBS) in movement disorders have recently become available. No
      guidelines exist for parameter adjustment after conversion of non-RC to RC IPGs,
      or reports of patient satisfaction with RC IPGs when used as initial DBS device
      or after conversion from non-RC IPGs. MATERIALS AND METHODS: Patients who
      underwent placement of Activa RC IPG (Medtronic, Inc.) were surveyed by phone
      about device satisfaction. Their charts were retrospectively reviewed and DBS
      settings were analyzed. The stimulation settings before and after conversion to
      RC were compared. RESULTS: Thirty-one patients (age 15-90; 18 male) with movement
      disorders (nine Parkinson's disease, nine dystonia, eight essential tremor, five
      others) were identified. Twelve subjects had initial RC IPG implantation; 19 were
      converted from non-RC IPGs (Soletra; Medtronic, Inc.) 2-14 years after initial
      DBS implant (mean 6.3 +/- 3.44 years). Twenty-six patients (17 conversions) were
      surveyed an average of 12.1 months since RC IPG implantation. Overall
      satisfaction with RC was high. Patients converted to RC were more likely to
      choose it again than those with initial RC. Patients denied differences in
      symptom control after conversion. Mean amplitude, pulse width, and frequency were
      slightly lower after conversion regardless of diagnosis and remained lower after
      three postconversion reprogramming with slow drift of amplitude back to
      preconversion settings, more in the GPi group. CONCLUSIONS: RC IPGs in DBS for
      movement disorders are well received by patients as initial therapy and after
      conversion. Mild reduction in stimulation parameters might be allowed after
      conversion to RC IPG.

PMID- 24112631
TI  - Timing of dialysis initiation in the geriatric population: toward a patient
      centered approach.
AB  - Over the last 10-15 years, the incidence of treated end-stage renal disease
      (ESRD) among older adults has increased and dialysis is being initiated at
      progressively higher levels of estimated glomerular filtration rate (eGFR).
      Average life expectancy after dialysis initiation among older adults is quite
      limited, and many experience an escalation of care and loss of independence after
      starting dialysis. Available data suggest that treatment decisions about dialysis
      initiation in older adults in the United States are guided more by system- than
      by patient-level factors. Stronger efforts are thus needed to ensure that
      treatment decisions for older adults with advanced kidney disease are optimally
      aligned with their goals and preferences. There is growing interest in more
      conservative approaches to the management of advanced kidney disease in older
      patients who prefer not to initiate dialysis and those for whom the harms of
      dialysis are expected to outweigh the benefits. A number of small single center
      studies, mostly from the United Kingdom report similar survival among the subset
      of older adults with a high burden of comorbidity treated with dialysis vs. those
      managed conservatively. However, the incidence of treated ESRD in older US adults
      is several-fold higher than in the United Kingdom, despite a similar prevalence
      of chronic kidney disease, suggesting large differences in the social, cultural,
      and economic context in which dialysis treatment decisions unfold. Thus, efforts
      may be needed to adapt conservative care models developed outside the United
      States to optimally meet the needs of US patients. More flexible approaches
      toward dialysis prescription and better integration of treatment decisions about
      conservative care with those related to modality selection will likely be helpful
      in meeting the needs of individual patients. Regardless of the chosen treatment
      strategy, time can often be a critical ally in centering care on what matters
      most to the patient, and a flexible and iterative approach of re-evaluation and
      redirection may often be needed to ensure that treatment strategies are fully
      aligned with patient priorities.

PMID- 24112632
TI  - Three-year incidence and factors associated with posterior capsule opacification
      after cataract surgery: The Australian Prospective Cataract Surgery and Age
      related Macular Degeneration Study.
AB  - PURPOSE: To assess 3-year incidence and associated factors of posterior capsule
      opacification (PCO) after phacoemulsification surgery. DESIGN: Cohort study.
      METHODS: A total of 1934 consecutive patients aged >=64 years undergoing
      phacoemulsification surgery at Westmead Hospital were recruited, of whom 1495
      (77.3%) had retroillumination anterior segment images taken of the surgical eyes
      after 1 month and at a further postoperative visit within 3 years. Severe PCO was
      defined if the view of the optic disc was obscured, or neodymium-yttrium-aluminum
      garnet capsulotomy was performed. Cumulative incidence of PCO was estimated using
      Kaplan-Meier methods. Associations of PCO with surgeon groups and different types
      of implanted intraocular lenses (IOLs) were assessed, adjusting for age, sex,
      diabetes, and ethnicity. RESULTS: Three-year cumulative incidence of PCO was
      38.5% (95% confidence interval [CI] 36.1%-40.9%) among the 1495 patients,
      including 4.7% (95% CI 3.5%-5.8%) with severe PCO. PCO incidence was higher in:
      (1) eyes operated on by junior trainees (49%) compared to those by senior
      ophthalmologist surgeons (36%) (adjusted odds ratio [OR] 1.6, 95% CI 1.2-2.0);
      and (2) eyes with hydrophobic, 3-piece (either square-edged [51%, OR 2.3, 95% CI
      1.4-3.6] or partial-round-edged [39%, OR 1.5, 95% CI 1.1-2.1]), or hydrophilic
      IOLs (64%, OR 2.9, 95% CI 1.9-4.4) compared to those with single-piece, square
      edged, hydrophobic IOLs (34%), after additional adjustment for surgeon group.
      CONCLUSIONS: Predominantly mild PCO occurred in one-third of eyes after
      phacoemulsification surgery. Possible predisposing factors associated with PCO
      development include surgery performed by ophthalmologic trainees and the use of
      hydrophilic or other hydrophobic IOLs apart from the single-piece, square-edged
      one.

PMID- 24112633
TI  - Eyelid sebaceous carcinoma: clinicopathologic and multiparametric
      immunohistochemical analysis that includes adipophilin.
AB  - PURPOSE: To evaluate the fine cytopathologic features and immunohistochemistry of
      eyelid sebaceous carcinoma. DESIGN: Retrospective clinicopathologic study.
      METHODS: Clinical records and microscopic glass slides of 12 patients diagnosed
      with sebaceous carcinoma were reviewed. Paraffin-embedded tissue recuts were
      immunoreacted for epithelial membrane antigen (EMA), Ber-EP4, p53, Ki-67, and
      adipophilin for cytoplasmic lipid. Invasive growth and intraepithelial spread
      were analyzed separately. Cytoplasmic and nuclear characteristics were correlated
      with the results of the immunohistochemical profiling. RESULTS: Five patients
      experienced recurrences, but no metastases or tumor-related deaths were
      discovered. The nuclei in 11 invasive tumor cells were typically round with
      finely divided, granular, or smudgy chromatin without prominent margination at
      the nuclear membrane; they exhibited small punctate nucleoli. Positivity for EMA
      (both diffuse and focal), p53 (72% of nuclei), and Ki-67 (45% proliferation
      index) was demonstrated. Adipophilin positivity in vesicular and granular forms
      was detected in paraffin sections in all invasive tumors, most prominently in
      moderately differentiated and well-differentiated lesions. Among 9 cases
      exhibiting intraepithelial extensions, 6 showed mostly granular positivity and 3
      vesicular positivity. p53 identified residual atypical intraepithelial cells when
      conjunctival epithelial sloughing occurred. CONCLUSIONS: Immunohistochemistry can
      make significant contributions to the diagnosis of sebaceous carcinoma. p53 and
      vesicular granular adipophilin positivity were highly reliable in supplementing
      the routine microscopic diagnosis of infiltrative tumors and both can be used in
      paraffin sections, thereby obviating cumbersome oil red O staining of frozen
      sections. The cells found in intraepithelial spread were strongly EMA and p53
      positive, with more granular than vesicular adipophilin positivity.

PMID- 24112634
TI  - Visual and refractive outcomes of femtosecond lenticule extraction and small
      incision lenticule extraction for myopia.
AB  - PURPOSE: To compare the visual and refractive outcomes of femtosecond lenticule
      extraction (FLEx) and small-incision lenticule extraction (SMILE) in eyes with
      myopia. DESIGN: Prospective, randomized, masked clinical trial with
      intraindividual comparison. METHODS: This study evaluated 52 eyes of 26
      consecutive patients with spherical equivalents of -4.19 +/- 1.65 diopters (D)
      (mean +/- standard deviation) who underwent FLEx in 1 eye and SMILE in the other
      eye by randomized assignment. Before surgery, and 1 week and 1, 3, and 6 months
      after surgery, we assessed safety, efficacy, predictability, stability, and
      adverse events of the 2 surgical techniques. RESULTS: LogMAR uncorrected and
      corrected distance visual acuity was, respectively, -0.17 +/- 0.10, -0.20 +/-
      0.07 in the FLEx group and -0.15 +/- 0.10, -0.19 +/- 0.07 in the SMILE group 6
      months postoperatively. In the FLEx and SMILE groups 6 months postoperatively,
      96% and 100% of eyes, respectively, were within 0.5 D of the targeted spherical
      equivalent correction. Changes of -0.02 +/- 0.39 D and 0.00 +/- 0.30 D occurred
      in manifest refraction from 1 week to 6 months in the FLEx and SMILE groups,
      respectively. No clinically significant complications occurred in the FLEx or the
      SMILE group. CONCLUSIONS: Both FLEx and SMILE performed well in the correction of
      myopia throughout the 6-month observation period. FLEx may be essentially
      equivalent to SMILE in terms of safety, efficacy, predictability, and stability,
      suggesting that the presence or absence of lifting the flap does not
      significantly affect these visual and refractive outcomes.

PMID- 24112635
TI  - Randomized controlled trial of intravitreal ranibizumab versus standard grid
      laser for macular edema following branch retinal vein occlusion.
AB  - PURPOSE: To assess the efficacy of intravitreal 0.5 mg ranibizumab for the
      treatment of center-involving macular edema secondary to branch retinal vein
      occlusion (BRVO) over 1 year compared with standard-of-care grid laser. DESIGN: A
      prospective randomized controlled clinical trial. METHODS: A total of 36 patients
      with vision loss in 1 eye attributable to macular edema following BRVO were
      recruited from 5 institutions. Patients were randomized 1:1 to a treatment group
      that received 6 monthly injections of 0.5 mg ranibizumab and thereafter monthly
      as needed based on best-corrected visual acuity (BCVA) and central foveal
      thickness (CFT) assessments on optical coherence tomography scans, or a standard
      of-care group that received monthly sham injections for the 1-year duration of
      the study. Grid laser was administered at 13 and 25 weeks in both groups if
      criteria for laser treatment were met. Main outcome measures included mean change
      in BCVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores from
      baseline to month 12. Secondary outcomes included anatomic outcomes and the
      percentage of patients requiring grid laser in both groups. RESULTS: Mean BCVA
      change from baseline was significantly greater in the treatment compared with the
      standard-of-care group at 12 months (12.5 ETDRS letters vs -1.6 ETDRS letters, P
      = .032). The mean CFT was significantly reduced in the treatment compared with
      standard-of-care group (361.7 MUm vs 175.6 MUm, P = .025). At 13 and 25 weeks,
      more patients in the standard-of-care group (68.4%, 50.0%) received grid laser
      than in the treatment group (6.7%, 8.3%). No new ocular or systemic adverse
      events were observed. CONCLUSIONS: Compared with standard grid laser,
      intravitreal ranibizumab provided significant and sustained benefits in visual
      acuity gain and anatomic improvement in eyes with macular edema secondary to
      BRVO.

PMID- 24112636
TI  - Induced resistance to Botrytis cinerea in Capsicum annuum by a Fusarium crude
      elicitor fraction, free of proteins.
AB  - Fusarium oxysporum f. sp. lycopersici (FOL) induces resistance in pepper against
      the airborne pathogen Botrytis cinerea and the soil-borne pathogen Verticillium
      dahliae. However, its practical use is limited due to its pathogenicity to other
      crops. In this study we tested several fractions of a heat-sterilised crude FOL
      elicitor preparation to protect pepper against B. cinerea and V. dahliae. Only
      the protein-free insoluble fraction of the preparation reduced B. cinerea
      infection. However, none of the fractions reduce V. dahliae symptoms. The
      insoluble protein-free fraction induced expression of defence genes in the plant,
      namely a chitinase (CACHI2), a peroxidase (CAPO1), a sesquiterpene cyclase
      (CASC1) and a basic PR1 (CABPR1). Even though the CASC1 gene was not induced
      directly after treatment with the insoluble fraction in the leaves, it was
      induced after B. cinerea inoculation, showing a priming effect. The insoluble
      protein-free FOL-elicitor protected pepper against the airborne pathogen through
      a mechanism that involves induced responses in the plant, but different to the
      living FOL. 

PMID- 24112637
TI  - Bologna guidelines for diagnosis and management of adhesive small bowel
      obstruction (ASBO): 2013 update of the evidence-based guidelines from the world
      society of emergency surgery ASBO working group.
AB  - BACKGROUND: In 2013 Guidelines on diagnosis and management of ASBO have been
      revised and updated by the WSES Working Group on ASBO to develop current evidence
      based algorithms and focus indications and safety of conservative treatment,
      timing of surgery and indications for laparoscopy. RECOMMENDATIONS: In absence of
      signs of strangulation and history of persistent vomiting or combined CT-scan
      signs (free fluid, mesenteric edema, small-bowel feces sign, devascularization)
      patients with partial ASBO can be managed safely with NOM and tube decompression
      should be attempted. These patients are good candidates for Water-Soluble
      Contrast-Medium (WSCM) with both diagnostic and therapeutic purposes. The
      radiologic appearance of WSCM in the colon within 24 hours from administration
      predicts resolution. WSCM maybe administered either orally or via NGT both
      immediately at admission or after failed conservative treatment for 48 hours. The
      use of WSCM is safe and reduces need for surgery, time to resolution and hospital
      stay.NOM, in absence of signs of strangulation or peritonitis, can be prolonged
      up to 72 hours. After 72 hours of NOM without resolution, surgery is
      recommended.Patients treated non-operatively have shorter hospital stay, but
      higher recurrence rate and shorter time to re-admission, although the risk of new
      surgically treated episodes of ASBO is unchanged. Risk factors for recurrences
      are age <40 years and matted adhesions. WSCM does not decrease recurrence rates
      or recurrences needing surgery.Open surgery is often used for strangulating ASBO
      as well as after failed conservative management. In selected patients and with
      appropriate skills, laparoscopic approach is advisable using open access
      technique. Access in left upper quadrant or left flank is the safest and only
      completely obstructing adhesions should be identified and lysed with cold
      scissors. Laparoscopic adhesiolysis should be attempted preferably if first
      episode of SBO and/or anticipated single band. A low threshold for open
      conversion should be maintained.Peritoneal adhesions should be prevented.
      Hyaluronic acid-carboxycellulose membrane and icodextrin decrease incidence of
      adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce
      need of surgery.Adhesions quantification and scoring maybe useful for achieving
      standardized assessment of adhesions severity and for further research in
      diagnosis and treatment of ASBO.

PMID- 24112638
TI  - Risk factors associated with slide positivity among febrile patients in a
      conflict zone of north-eastern Myanmar along the China-Myanmar border.
AB  - BACKGROUND: Malaria within the Greater Mekong sub-region is extremely
      heterogeneous. While China and Thailand have been relatively successful in
      controlling malaria, Myanmar continues to see high prevalence. Coupled with the
      recent emergence of artemisinin-resistant malaria along the Thai-Myanmar border,
      this makes Myanmar an important focus of malaria within the overall region.
      However, accurate epidemiological data from Myanmar have been lacking, in part
      because of ongoing and emerging conflicts between the government and various
      ethnic groups. Here the results are reported from a risk analysis of malaria
      slide positivity in a conflict zone along the China-Myanmar border. METHODS:
      Surveys were conducted in 13 clinics and hospitals around Laiza City, Myanmar
      between April 2011 and October 2012. Demographic, occupational and educational
      information, as well as malaria infection history, were collected. Logistic
      models were used to assess risk factors for slide positivity. RESULTS: Age
      patterns in Plasmodium vivax infections were younger than those with Plasmodium
      falciparum. Furthermore, males were more likely than females to have falciparum
      infections. Patients who reported having been infected with malaria during the
      previous year were much more likely to have a current vivax infection. During the
      second year of the study, falciparum infections among soldiers increased
      signficiantly. CONCLUSIONS: These results fill some knowledge gaps with regard to
      risk factors associated with malaria slide positivity in this conflict region of
      north-eastern Myanmar. Since epidemiological studies in this region have been
      rare or non-existent, studies such as the current are crucial for understanding
      the dynamic nature of malaria in this extremely heterogeneous epidemiological
      landscape.

PMID- 24112640
TI  - The spectrum of factor XI deficiency in Italy.
AB  - Factor XI (FXI) deficiency is a rare inherited bleeding disorder invariably
      caused by mutations in the FXI gene. The disorder is rather frequent in Ashkenazi
      Jews, in whom around 98% of the abnormal alleles is represented by Glu117X and
      Phe283Leu mutations. A wide heterogeneity of causative mutations has been
      previously reported in a few FXI deficient patients from Italy. In this article,
      we enlarge the knowledge on the genetic background of FXI deficiency in Italy.
      Over 4 years, 22 index cases, eight with severe deficiency and 14 with partial
      deficiency, have been evaluated. A total of 21 different mutations in 30 disease
      associated alleles were identified, 10 of which were novel. Among them, a novel
      Asp556Gly dysfunctional mutation was also identified. Glu117X was also detected,
      as previously reported from other patients in Italy, while again Phe283Leu was
      not identified. A total of 34 heterozygous relatives were also identified.
      Bleeding tendency was present in very few cases, being inconsistently related to
      the severity of FXI deficiency in plasma. In conclusion, at variance with other
      populations, no single major founder effect is present in Italian patients with
      FXI deficiency.

PMID- 24112639
TI  - MicroRNA-146 function in the innate immune transcriptome response of zebrafish
      embryos to Salmonella typhimurium infection.
AB  - BACKGROUND: MicroRNAs (miRNAs) have recently been shown to play important roles
      in development of the immune system and in fine-tuning of immune responses. Human
      miR-146 family members are known as inflammation-inducible miRNAs involved in
      negative feedback regulation of Toll-like receptor (TLR) signalling.
      Dysregulation of the miR-146 family has often been linked to inflammatory
      diseases and malignancies. This study reports on miR-146a and miR-146b as
      infection-inducible miRNAs in zebrafish, which has emerged as a model species for
      human disease. RESULTS: Using a custom-designed microarray platform for miRNA
      expression we found that both members of the zebrafish miR-146 family, miR-146a
      and miR-146b, were commonly induced by infection of zebrafish embryos with
      Salmonella typhimurium and by infection of adult fish with Mycobacterium marinum.
      The induction of these miRNAs was confirmed by Taqman miRNA assays. Subsequently,
      we used zebrafish embryos, in which adaptive immunity is not yet active, as an in
      vivo system to investigate the role of miR-146 in the innate immune response to
      S. typhimurium infection. Knockdown of traf6 and use of myd88 mutants
      demonstrated that the induction of miR-146a and miR-146b by S. typhimurium
      infection was affected by disruption of the MyD88-Traf6 pathway that mediates
      transduction of TLR signals and cytokine responses. In turn, knockdown of miR-146
      itself had no major effects on the expression of known targets of MyD88-Traf6
      signalling. Instead, RNA sequencing analysis showed that miR-146 knockdown led to
      an increased induction of six members of the apolipoprotein gene family in S.
      typhimurium-infected embryos. CONCLUSION: Based on microarray analysis and Taqman
      miRNA assays we conclude that members of the miR-146 family, which is highly
      conserved between fish and human, are induced by bacterial infection in zebrafish
      in a MyD88 and Traf6 dependent manner. The combined knockdown of miR-146a and miR
      146b in zebrafish embryos infected with S. typhimurium had no major effect on the
      expression of pro-inflammatory genes and transcription factors known to be
      downstream of the MyD88-Traf6 pathway. In contrast, apolipoprotein-mediated lipid
      transport emerged as an infection-inducible pathway under miR-146 knockdown
      conditions, suggesting a possible function of miR-146 in regulating lipid
      metabolism during inflammation.

PMID- 24112641
TI  - Fetal and neonatal samples of a precursor surfactant protein B inversely related
      to gestational age.
AB  - BACKGROUND: Alveolar-capillary membrane leaks can increase the amount of
      surfactant protein B (SP-B) in the bloodstream. The purpose of this study was to
      measure the concentration of C-proSP-B, a SP-B precursor that includes C-terminal
      domains, in various body fluids of newborn infants and determine its dependence
      on gestational age. METHODS: C-pro-SPB was measured in amniotic fluid and
      umbilical cord blood at birth, and in peripheral blood and urine on postnatal day
      3 in 137 newborn infants with a median birth weight of 2015 g (range, 550-4475 g)
      and gestational age of 34 weeks (range, 23-42 weeks). RESULTS: C-proSP-B levels
      differed more than 100-fold among samples. The levels (median; interquartile
      range) were highest in peripheral blood (655.6 ng/mL; 419.0-1467.0 ng/mL) and
      lowest in urine (3.08 ng/mL; 2.96-3.35 ng/mL). C-proSP-B levels in amniotic fluid
      (314.9 ng/mL; 192.7-603.6 ng/mL) were approximately half of those in peripheral
      blood. In cord blood C-proSP-B was slightly lower (589.1 ng/mL; 181.2-1129.0
      ng/mL) compared with peripheral blood. C-proSP-B levels significantly increased
      in all the fluids sampled except urine with decreasing gestational age (p <
      0.001). CONCLUSIONS: This novel assay allows for the quantitative measurement of
      C-proSP-B in blood and amniotic fluid. The dependence of C-proSP-B on gestational
      age may hamper its use for the detection of alveolar leaks in preterm newborns.

PMID- 24112642
TI  - Revisiting the connectivity puzzle of the common coral Pocillopora damicornis.
AB  - Understanding levels of connectivity among scleractinian coral populations over a
      range of temporal and spatial scales is vital for managing tropical coral reef
      ecosystems. Here, we use multilocus microsatellite genotypes to assess the
      spatial genetic structure of two molecular operational taxonomic units (MOTUs,
      types alpha and beta) of the widespread coral Pocillopora damicornis on the Great
      Barrier Reef (GBR) and infer the extent of connectivity on spatial scales
      spanning from local habitat types to latitudinal sectors of the GBR. We found
      high genetic similarities over large spatial scales spanning > 1000 km from the
      northern to the southern GBR, but also strong genetic differentiation at local
      scales in both MOTUs. The presence of a considerable number of first-generation
      migrants within the populations sampled (12% and 27% for types alpha and beta,
      respectively) suggests that genetic differentiation over small spatial scales is
      probably a consequence of stochastic recruitment from different genetic pools
      into recently opened up spaces on the reef, for example, following major
      disturbance events. We explain high genetic similarity among populations over
      hundreds of kilometres by long competency periods of brooded zooxanthellate
      larvae and multiple larval release events each year, combined with strong
      longshore currents typical along the GBR. The lack of genetic evidence for
      predominantly clonal reproduction in adult populations of P. damicornis, which
      broods predominantly asexually produced larvae, further undermines the paradigm
      that brooded larvae settle close to parent colonies shortly after the release. 

PMID- 24112643
TI  - Adaptive comanagement of a marine protected area network in Fiji.
AB  - Adaptive management of natural resources is an iterative process of decision
      making whereby management strategies are progressively changed or adjusted in
      response to new information. Despite an increasing focus on the need for adaptive
      conservation strategies, there remain few applied examples. We describe the 9
      year process of adaptive comanagement of a marine protected area network in
      Kubulau District, Fiji. In 2011, a review of protected area boundaries and
      management rules was motivated by the need to enhance management effectiveness
      and the desire to improve resilience to climate change. Through a series of
      consultations, with the Wildlife Conservation Society providing scientific input
      to community decision making, the network of marine protected areas was
      reconfigured so as to maximize resilience and compliance. Factors identified as
      contributing to this outcome include well-defined resource-access rights;
      community respect for a flexible system of customary governance; long-term
      commitment and presence of comanagement partners; supportive policy environment
      for comanagement; synthesis of traditional management approaches with systematic
      monitoring; and district-wide coordination, which provided a broader spatial
      context for adaptive-management decision making. Co-Manejo Adaptativo de una Red
      de Areas Marinas Protegidas en Fiyi. 

PMID- 24112644
TI  - A coordinated MIMO control design for a power plant using improved sliding mode
      controller.
AB  - For the participation of the steam power plants in regulating the network
      frequency, boilers and turbines should be co-ordinately controlled in addition to
      the base load productions. Lack of coordinated control over boiler-turbine may
      lead to instability; oscillation in producing power and boiler parameters;
      reduction in the reliability of the unit; and inflicting thermodynamic tension on
      devices. This paper proposes a boiler-turbine coordinated multivariable control
      system based on improved sliding mode controller (ISMC). The system controls two
      main boiler-turbine parameters i.e., the turbine revolution and superheated steam
      pressure of the boiler output. For this purpose, a comprehensive model of the
      system including complete and exact description of the subsystems is extracted.
      The parameters of this model are determined according to our case study that is
      the 320MW unit of Islam-Abad power plant in Isfahan/Iran. The ISMC method is
      simulated on the power plant and its performance is compared with the related
      real PI (proportional-integral) controllers which have been used in this unit.
      The simulation results show the capability of the proposed controller system in
      controlling local network frequency and superheated steam pressure in the
      presence of load variations and disturbances of boiler. 

PMID- 24112645
TI  - Novel intelligent real-time position tracking system using FPGA and fuzzy logic.
AB  - The main aim of this paper is to test if FPGAs are able to achieve better
      position tracking performance than software-based soft real-time platforms. For
      comparison purposes, the same controller design was implemented in these
      architectures. A Multi-state Fuzzy Logic controller (FLC) was implemented both in
      a Xilinx((r)) Virtex-II FPGA (XC2v1000) and in a soft real-time platform NI
      CompactRIO((r))-9002. The same sampling time was used. The comparative tests were
      conducted using a servo-pneumatic actuation system. Steady-state errors lower
      than 4 MUm were reached for an arbitrary vertical positioning of a 6.2 kg mass
      when the controller was embedded into the FPGA platform. Performance gains up to
      16 times in the steady-state error, up to 27 times in the overshoot and up to
      19.5 times in the settling time were achieved by using the FPGA-based controller
      over the software-based FLC controller.

PMID- 24112646
TI  - A new and simple method to construct root locus of general fractional-order
      systems.
AB  - Recently fractional-order (FO) differential equations are widely used in the
      areas of modeling and control. They are multivalued in nature hence their
      stability is defined using Riemann surfaces. The stability analysis of FO linear
      systems using the technique of Root Locus is the main focus of this paper.
      Procedure to plot root locus of FO systems in s-plane has been proposed by many
      authors, which are complicated, and analysis using these methods is also
      difficult and incomplete. In this paper, we have proposed a simple method of
      plotting root locus of FO systems. In the proposed method, the FO system is
      transformed into its integer-order counterpart and then root locus of this
      transformed system is plotted. It is shown with the help of examples that the
      root locus of this transformed system (which is obviously very easy to plot) has
      exactly the same shape and structure as the root locus of the original FO system.
      So stability of the FO system can be directly deduced and analyzed from the root
      locus of the transformed IO system. This proposed procedure of developing and
      analyzing the root locus of FO systems is much easier and straightforward than
      the existing methods suggested in the literature. This root locus plot is used to
      comment about the stability of FO system. It also gives the range for the
      amplifier gain k required to maintain this stability. The reliability of the
      method is verified with analytical calculations. 

PMID- 24112647
TI  - No human virus sequences detected by next-generation sequencing in benign
      verrucous skin tumors occurring in BRAF-inhibitor-treated patients.
AB  - Patients treated with BRAF inhibitors (e.g. vemurafenib), a novel targeted
      therapy for advanced melanoma harbouring certain BRAF mutations, develop numerous
      adverse cutaneous side effects, including skin tumors such as squamous cell
      carcinoma or non-malignant verruciform keratinocyte proliferations, termed 'BRAF
      inhibitor-associated verrucous keratosis (BAVK) lesions'. These keratinocyte
      proliferations are believed to be caused by paradoxical hyperactivation of the
      MAPK pathway in cells with wild-type BRAF, but mutated RAS. However, due to the
      clinical and histological verruca-like appearance of these lesions, additional
      aetiologic cofactors, such as infectious agents (i.e. oncogenic viruses), might
      be suspected. Therefore, we performed 454 high-throughput sequencing of BAVK
      lesions from vemurafenib-treated patients on the transcript level to identify
      actively transcribed viral sequences of known [e.g. human papilloma viruses
      (HPV)] or even yet-unknown viruses. Next-generation sequencing did not identify
      transcripts of any human viruses out of 1 595 161 reads obtained from BAVK
      lesions of four patients. Nevertheless, all controls were recognized correctly,
      and the detection of sequences derived from the cutaneous microbiome (e.g. skin
      commensals and bacterial phages) confirmed the validity and sensitivity of the
      sequencing data. Our results are consistent with preliminary histological and
      immunohistochemical findings recently reported by others, who also failed to
      detect the expression of HPV proteins in BAVK. Although the patient number is
      limited and we cannot exclude the possibility of having missed a viral transcript
      of very low abundance, our study argues against a viral aetiology of BRAF
      inhibitor-associated verruciform keratoses occurring under vemurafenib. 

PMID- 24112648
TI  - Naturally occurring melanomas in dogs as models for non-UV pathways of human
      melanomas.
AB  - Spontaneously occurring melanomas are frequent in dogs. They appear at the same
      localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They
      display variable behaviors: tumors at oral localizations are more frequent and
      aggressive than at other anatomical sites. Interestingly, dog melanomas are
      associated with strong breed predispositions and overrepresentation of black
      coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles
      are at high risk of developing oral melanoma, while schnauzers or Beauce
      shepherds mostly developped cutaneous melanoma. Clinical and histopathological
      analyses were performed on a cohort of 153 cases with a 4-yr follow-up.
      Histopathological characterization showed that most canine tumors are intradermal
      and homologous to human rare morphological melanomas types - 'nevocytoid type'
      and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six
      genes, relevant to human melanoma classification, detected somatic mutations in
      oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF.
      Altogether, these findings support the relevance of the dog model for comparative
      oncology of melanomas, especially for the elucidation of non-UV induced pathways.

PMID- 24112650
TI  - Delayed orthodontic extrusion of a traumatically intruded immature upper
      permanent incisor - a case report.
AB  - Dental injuries are probably the most common orofacial injuries sustained during
      sports and play. Intrusion or intrusive luxations occur when the teeth are driven
      into the alveolus by an axially directed impact. This article describes the
      clinical case of an 8-year-old patient who suffered complete intrusive luxation
      of an immature permanent central incisor following an accident. An attempt at
      spontaneous re-eruption failed to facilitate re-emergence of the tooth beyond 2
      mm. The recommended wait-and-see strategy in anticipation of spontaneous re
      eruption should cease to be an option when no further elongation can be observed.
      Orthodontic extrusion or surgical re-positioning is a valid treatment alternative
      when the former fails. In this case, although the recommended time period for
      effecting orthodontic extrusion had elapsed, this procedure was undertaken
      successfully presumably owing to the application of controlled, biologically
      optimal forces. A review of the extruded tooth a year later revealed no clinical
      or radiographic signs of loss of vitality. This was confirmed radiographically by
      the completion of root development, an intact lamina dura and no evident signs of
      resorption.

PMID- 24112649
TI  - Comparative study of SoxR activation by redox-active compounds.
AB  - SoxR from Escherichia coli and related enterobacteria is activated by a broad
      range of redox-active compounds through oxidation or nitrosylation of its [2Fe
      2S] cluster. Activated SoxR then induces SoxS, which subsequently activates more
      than 100 genes in response. In contrast, non-enteric SoxRs directly activate
      their target genes in response to redox-active compounds that include
      endogenously produced metabolites. We compared the responsiveness of SoxRs from
      Streptomyces coelicolor (ScSoxR), Pseudomonas aeruginosa (PaSoxR) and E. coli
      (EcSoxR), all expressed in S. coelicolor, towards natural or synthetic redox
      active compounds. EcSoxR responded to all compounds examined, whereas ScSoxR was
      insensitive to oxidants such as paraquat (Eh -440 mV) and menadione sodium
      bisulphite (Eh -45 mV) and to NO generators. PaSoxR was insensitive only to some
      NO generators. Whole-cell EPR analysis of SoxRs expressed in E. coli revealed
      that the [2Fe-2S](1+) of ScSoxR was not oxidizable by paraquat, differing from
      EcSoxR and PaSoxR. The mid-point redox potential of purified ScSoxR was
      determined to be -185 +/- 10 mV, higher by approximately 100 mV than those of
      EcSoxR and PaSoxR, supporting its limited response to paraquat. The overall
      sensitivity profile indicates that both redox potential and kinetic reactivity
      determine the differential responses of SoxRs towards various oxidants.

PMID- 24112651
TI  - How not to do kinetics: examples involving GTPases and guanine nucleotide
      exchange factors.
AB  - Guanine nucleotide exchange factors (GEFs) are crucial regulators of the action
      of GTPases in signal transduction and cellular regulation. Although their basic
      mechanism of action has been apparent for almost 20 years, there are still
      misconceptions concerning their properties, and these are confounded by
      superficial or incorrect interpretation of experimental results in individual
      cases. Here, an example is described in which an incorrect mechanism was derived
      because of an inadequate analysis of kinetic results. In a second example, a case
      is discussed where certain GTP analogs were erroneously described as being able
      to function as low molecular mass GEFs. In both cases, a lack of distinction
      between rates, rate constants, and apparent rate constants, together with a
      disregard of relative signal amplitudes, led to the misinterpretations. In a
      final example, it is shown how the lack of an appropriate kinetic investigation
      led to the false conclusion that a secreted protein from Legionella pneumophila
      can act not only as a GEF towards eukaryotic Rab1 but also as a factor that is
      able to actively dissociate the stable complex between Rab1 and GDP dissociation
      inhibitor.

PMID- 24112652
TI  - Higher rates of upgrading and upstaging in older patients undergoing radical
      prostatectomy and qualifying for active surveillance.
AB  - OBJECTIVE: To determine pathological and oncological outcomes of patients
      diagnosed with low-risk prostate cancer in two age cohorts who underwent radical
      prostatectomy (RP) and qualified for active surveillance (AS) according to
      Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, as
      AS for low-risk prostate cancer represents an acceptable management strategy
      especially for older patients. PATIENTS AND METHODS: In all, 320 patients aged
      >=65 years who underwent RP and were eligible for AS according to PRIAS criteria
      were propensity score matched 1:1 to patients aged <65 years. Patient
      characteristics were compared with chi-square, Kruskal-Wallis, and one-way anova
      tests. Predictors of RP pathological upgrading or upstaging were analysed using
      logistic regression. Recurrence-free survival (RFS) and overall survival (OS)
      were calculated using the Kaplan-Meier method. Predictors of RFS were analysed
      within Cox regression models. RESULTS: Pathological upgrading and upstaging were
      significantly higher among older (>=65 years) vs younger (<65 years) patients
      (53.1% vs 44.1% and 12.2% vs 7.2%, respectively). Higher prostate-specific
      antigen levels and increasing age were independent predictors of upgrading among
      patients aged <65 years. There were no differences in RFS or OS between the two
      age groups. Positive surgical margin status was the only independent predictor of
      shorter RFS. CONCLUSIONS: Patients aged >=65 years who are eligible for AS by
      PRIAS criteria have a higher risk of being upgraded and upstaged at RP than those
      aged <65 years. These findings should be taken into consideration when discussing
      treatment options for patients diagnosed with prostate cancer.

PMID- 24112653
TI  - Preparation of reference stocks suitable for evaluation of alternative NAT-based
      mycoplasma detection methods.
AB  - AIMS: The aim of this study was to optimize conditions for preparation and
      cryopreservation of mycoplasma reference materials suitable to evaluate
      alternative nucleic acid testing (NAT)-based assays and to compare their limits
      of detection (LODs) with those of conventional culture-based methods. METHODS AND
      RESULTS: Acholeplasma laidlawii, Mycoplasma gallisepticum and Mycoplasma arginini
      stocks with low ratios of genomic copies to colony forming units (12, 8 and 4,
      respectively) harvested in early stationary phases of growth were preserved with
      different cryoprotective agents (CPAs) under slow (1 degrees C min(-1)), moderate
      (8 degrees C min(-1)), fast (13 degrees C min(-1)) and 'snapshot' (60 degrees C
      min(-1)) cooling rates. Depending on mycoplasma species, increasing the cooling
      rate from slow to snapshot enhanced cell survival up to 5-fold. The addition of
      10% (v/v) dimethyl sulfoxide (DMSO) and 15% (v/v) glycerol significantly improved
      cell survival of all tested strains. Cryoprotected stocks maintained high and
      stable titres for at least 1 year during storage at -80 degrees C. Sonication of
      cell cultures prior to cryopreservation enhanced cell dispersion and reduced of
      GC/CFU ratios. CONCLUSIONS: It is feasible to prepare stable reference stocks of
      cryopreserved mycoplasma cells suitable to reliably compare NAT- and culture
      based mycoplasma testing methods. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study describes experimental results demonstrating the preparation and storage of
      highly viable and dispersed mycoplasma reference stocks suitable for comparing
      alternative NAT-and conventional culture-based mycoplasma detection methods.

PMID- 24112654
TI  - Contamination of polychlorinated biphenyls and organochlorine pesticides in
      breast milk in Korea: time-course variation, influencing factors, and exposure
      assessment.
AB  - Breast milk is a noninvasive specimen to assess maternal and infant exposure to
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). In this
      study, 206 breast milk samples were collected from 87 participants during
      lactation, at <7, 15, 30, or 90 days postpartum in four cities in Korea. The
      total concentrations of PCBs (SigmaPCB) and OCPs (SigmaOCP) ranged from <LOQ to
      84.0 (median: 12.1) ng g(-1) lipid weight and from <LOQ to 559 (median: 144) ng
      g(-1) lipid weight, respectively. The residue levels of these contaminants
      measured in our study were relatively lower than those reported for European,
      African and Asian populations. Within a month postpartum typically after day
      seven the levels of SigmaPCB and SigmaOCP significantly increased. Some OCP
      compounds were correlated with maternal age, BMI, parity, and delivery mode.
      Certain types of dietary habits such as seafood and noodle consumption were
      significantly associated with SigmaPCB and SigmaOCP. The estimated daily intakes
      (EDIs) of SigmaPCB and SigmaOCP were 45.2-127 ng kg(-1) bw day(-1) and 625-1259
      ng kg(-1) bw day(-1) during lactation, respectively, which are lower than the
      threshold values proposed by the US EPA and Health Canada. The exposure of Korean
      infants to chlordanes via breast milk had a potential health risk which deserves
      further investigation.

PMID- 24112655
TI  - Effects of input uncertainty and variability on the modelled environmental fate
      of organic pollutants under global climate change scenarios.
AB  - Global climate change (GCC) is expected to influence the fate, exposure and risks
      of organic pollutants to wildlife and humans. Multimedia chemical fate models
      have been previously applied to estimate how GCC affects pollutant concentrations
      in the environment and biota, but previous studies have not addressed how
      uncertainty and variability of model inputs affect model predictions. Here, we
      assess the influence of climate variability and chemical property uncertainty on
      future projections of environmental fate of six polychlorinated biphenyl
      congeners under different GCC scenarios using a spreadsheet version of the
      ChemCAN model and the Crystal Ball(r) software. Regardless of emission mode,
      results demonstrate: (i) uncertainty in degradation half-lives dominates the
      variance of modelled absolute levels of PCB congeners under GCC scenarios; (ii)
      when the ratios of predictions under GCC to predictions under present day climate
      are modelled, climate variability dominates the variance of modelled ratios; and
      (iii) the ratios also indicate a maximum of about a factor of 2 change in the
      long-term average environmental concentrations due to GCC that is forecasted
      between present conditions and the period between 2080 and 2099. We conclude that
      chemical property uncertainty does not preclude assessing relative changes in a
      GCC scenario compared to a present-day scenario if variance in model outputs due
      to chemical properties and degradation half-lives can be assumed to cancel out in
      the two scenarios. 

PMID- 24112656
TI  - Serum levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans
      and polychlorinated biphenyls in a population living in the Naples area, southern
      Italy.
AB  - The objective of this study was to estimate the levels of polychlorinated dibenzo
      p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated
      biphenyls (DL-PCBs and NDL-PCBs) in blood serum obtained from non-occupationally
      exposed volunteers living in the Naples area (Campania Region, southern Italy).
      The samples were taken from two geographical zones: one was an urban area of
      Naples and its surroundings and the other was located in an area deemed to be at
      high environmental risk. Total mean concentrations of these persistent pollutants
      proved to be in the range 1.43-17.38 pg WHO-TEQ1998 g(-1) lipid for PCDD/Fs, and
      0.98-25.45 pg WHO-TEQ1998 g(-1) lipid for DL-PCBs. NDL-PCBs were in the range
      316.57-482.90 ng g(-1) lipid. No significant differences were observed between
      women and men, nor between donors living in the two different areas. The mean
      levels of PCDD/Fs and PCBs in the population living in the Naples area were lower
      than those observed in some studies of populations living in exposed areas (near
      incineration plants or industrial sites) and urban or rural areas.

PMID- 24112657
TI  - Indigenous microbes survive in situ ozonation improving biodegradation of
      dissolved organic matter in aged oil sands process-affected waters.
AB  - The oil sands industry faces significant challenges in developing effective
      remediation technologies for process-affected water stored in tailings ponds.
      Naphthenic acids, a complex mixture of cycloaliphatic carboxylic acids, have been
      of particular concern because they concentrate in tailings ponds and are a
      component of the acutely toxic fraction of process water. Ozone treatment has
      been demonstrated as an effective means of rapidly degrading naphthenic acids,
      reducing process water toxicity, and increasing its biodegradability following
      seeding with the endogenous process water bacteria. This study is the first to
      examine subsequent in situ biodegradation following ozone pretreatment. Two aged
      oil sands process-affected waters from experimental reclamation tailings ponds
      were ozonated to reduce the dissolved organic carbon, to which naphthenic acids
      contributed minimally (<1mgL(-1)). Treatment with an ozone dose of 50mgL(-1)
      improved the 84d biodegradability of remaining dissolved organic carbon during
      subsequent aerobic incubation (11-13mgL(-1) removed from aged process-affected
      waters versus 5mgL(-1) when not pretreated with ozone). The ozone-treated
      indigenous microbial communities were as capable of degrading organic matter as
      the same community not exposed to ozone. This supports ozonation coupled with
      biodegradation as an effective and feasible treatment option. 

PMID- 24112658
TI  - Development of enzyme-linked immunosorbent assay (ELISA) for glutathione S
      transferase (GST-S) protein in the intertidal copepod Tigriopus japonicus and its
      application for environmental monitoring.
AB  - To utilize the GST-S protein as a useful biomarker for environmental
      contamination, we developed a polyclonal antibody-based enzyme-linked
      immunosorbent assay (ELISA) in the intertidal copepod Tigriopus japonicus. Two
      polyclonal antibodies, TJ-GST-S1 and TJ-GST-S2, were raised against two TJ-GST-S
      synthetic peptides. Also a recombinant TJ-GST-S protein was purified as a
      standard for ELISA development. Each polyclonal antibody was tested by Western
      blot analysis and indirect ELISA. Of two polyclonal antibodies, TJ-GST-S2 ELISA
      was further employed due to its wide range of detection and the limit of
      specificity compared to those of TJ-GST-S1 ELISA system. After exposure to 4
      metals (Ag, As, Cd, and Cu) to T. japonicus, the amount of TJ-GST-S protein was
      significantly elevated in a concentration-dependent manner. Also, TJ-GST-S
      protein was upregulated at relative high concentrations of B[alpha]P, PCB, and
      TBT. In this paper, we suggest that T. japonicas ELISA for TJ-GST-S2 is useful as
      a potential indicator system for marine contaminants. 

PMID- 24112659
TI  - Sources of unintentionally produced polychlorinated naphthalenes.
AB  - The European Union has proposed that polychlorinated naphthalenes (PCNs) should
      be included in the annexes of the Stockholm Convention on Persistent Organic
      Pollutants, signifying that there will be an increase in activities aimed at
      reducing PCN emissions. It has been speculated that the unintentional formation
      and emission of PCNs from industrial activities are the main current sources,
      because they have ceased to be manufactured as industrial chemicals in many
      countries. In this review, we provide a brief overview of recent progress in
      research into the unintentional formation and emission of PCNs from various
      industries that use thermal processes. The sampling and analysis of PCNs, and
      their formation mechanisms during thermal processes, are reviewed and discussed.
      The emission levels, emission profiles, and emission factors of PCNs from a
      number of industries that use thermal processes are summarized and compared, and
      this will provide helpful information for planning PCN source control measures
      and studying the source-receptor relationships of PCNs. 

PMID- 24112660
TI  - Visible light-induced decomposition of a fluorotelomer unsaturated carboxylic
      acid in water with a combination of tungsten trioxide and persulfate.
AB  - Photochemical decomposition of a fluorotelomer unsaturated carboxylic acid,
      C3F7CFCHCOOH (1), in the presence of WO3 and an electron acceptor (S2O8(2-) or
      H2O2) in water under visible-light irradiation was investigated. Under an O2
      atmosphere, 1 was not decomposed either by TiO2 (P25) or WO3 alone. A combination
      of WO3 and H2O2 also resulted in almost no decomposition of 1. In contrast,
      irradiation in the presence of a combination of WO3 and S2O8(2-) (potassium salt)
      efficiently decomposed 1 to F(-), CO2, C3F7COOH, and C2F5COOH. The decomposition
      of 1 was affected by the counter cation of S2O8(2-): the decomposition extent was
      higher with K2S2O8 than with (NH4)2S2O8. The decomposition of 1 was further
      enhanced when the reaction in the presence of WO3 and K2S2O8 was carried out
      under an argon atmosphere. Under O2, the amount of H2O2 formed in the reaction
      solution was an order of magnitude higher than the amount formed under argon.
      This fact suggests that the decrease in the decomposition of 1 under O2 can be
      ascribed to the formation of H2O2, which consumed S2O8(2-) and SO4(-). 

PMID- 24112661
TI  - Comparison of aneroid and oscillometric blood pressure measurements in children.
AB  - Limited data exist on the comparison of blood pressure (BP) measurements using
      aneroid and oscillometric devices. The purpose of the study was to investigate
      the difference in BP obtained using oscillometric and aneroid BP monitors in 9-
      to 10-year-old children. A total of 979 children were divided into group O, which
      underwent two oscillometric BP readings followed by two aneroid readings, and
      group A, which had BP measured in the reverse order. No significant difference
      was found between the mean (+/-standard deviation) of the two systolic BP
      readings obtained using the oscillometric and aneroid devices (111.5+/-8.6 vs
      111.3+/-8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the
      oscillometric monitor (61.5+/-8.0 vs 64.5+/-6.8 mm Hg; P<.001). A significant
      downward trend in BP was observed with each consecutive measurement, and
      agreement between the two monitors was limited. Multiple BP measurements are,
      therefore, recommended before the diagnosis of elevated BP or hypertension is
      made with either method. 

PMID- 24112662
TI  - Striatal somatotopy and motor responses evoked by acute electrical stimulation of
      the posterior striatum in rats.
AB  - INTRODUCTION/OBJECTIVES: Previous experiments suggest that the striatal
      sensorimotor territory in rats is located in its dorsolateral region, along the
      rostrocaudal axis, unlike what has been observed in primates. In the present
      study, electrical stimulation was performed to investigate the degree of
      participation of the posterior striatum in its motor territory, its somatotopic
      organization, and the motor responses evoked by stimulation. METHODS: Twenty-five
      rats were submitted to stereotactic stimulation of the posterior striatum under
      general anesthesia, receiving consecutively four different current intensities.
      The motor responses observed in the different body parts were registered for
      later comparison. We considered as threshold the smallest of these current
      intensities able to evoke a motor response. RESULTS: The observed motor responses
      were qualitatively different for each segment: forepaws: ipsilateral, adduction,
      and contralateral abduction; hindpaws: ipsilateral, flexion, and contralateral,
      extension/abduction; trunk, rotation/flexion; and tail, rotation/elevation. High
      frequency, small-amplitude distal tremor occurred in the ipsilateral forepaw in
      95% of the animals. Progressively larger current intensities were necessary for
      the induction of motor response in the forepaws, hindpaws, and trunk/tail, in
      that order. CONCLUSIONS: The results allowed us to infer the following posterior
      striatal somatotopic organization: forepaws, posterolaterally, being the
      contralateral medial to the ipsilateral; trunk/tail, anteromedially; and
      hindpaws, in an intermediate position, being the contralateral posterior to the
      ipsilateral. It is suggested that the tremor and the other observed motor
      responses derive from the excitation of striatal projection neurons and that the
      striatum may play an important role in the genesis of essential tremor.

PMID- 24112663
TI  - Fish oil protects the peripheral and central nervous systems against cisplatin
      induced neurotoxicity.
AB  - OBJECTIVE: The protective effects of fish oil (FO) on cisplatin (CP)-induced
      central and peripheral neurotoxicity were investigated in rats. METHODS: Rats (n
      = 28) were divided equally into four groups, the first group was kept as a
      control. In the second and third groups, CP and FO were given at doses of 7 mg/kg
      and 1 softgel/rat/day, respectively. In the fourth group, CP and FO were given
      together at the same doses. RESULTS: Although CP caused significant oxidative
      damage, via induction of lipid peroxidation and reduction in the antioxidant
      defense system potency, FO treatment largely reversed these effects. CP also
      resulted in histopathological damage, such as apoptosis, and electromyographical
      changes in the sciatic nerve. FO treatment partially prevented the
      histopathological and electromyographical effects of CP. DISCUSSION: CP has
      severe central and peripheral neurotoxic effects in rats and these effects were
      largely prevented by FO treatment. Thus, it appears that co-administration of FO
      with CP may be a useful approach to attenuate the negative effects of CP on the
      nervous system.

PMID- 24112664
TI  - Cell proliferation and plant development under novel altered gravity
      environments.
AB  - Gravity is a key factor for life on Earth. It is the only environmental factor
      that has remained constant throughout evolution, and plants use it to modulate
      important physiological activities; gravity removal or alteration produces
      substantial changes in essential functions. For root gravitropism, gravity is
      sensed in specialised cells, which are capable of detecting magnitudes of the g
      vector lower than 10(-3) . Then, the mechanosignal is transduced to upper zones
      of the root, resulting in changes in the lateral distribution of auxin and in the
      rate of auxin polar transport. Gravity alteration has consequences for cell
      growth and proliferation rates in root meristems, which are the basis of the
      developmental programme of a plant, in which regulation via auxin is involved.
      The effect is disruption of meristematic competence, i.e. the strict coordination
      between cell proliferation and growth, which characterises meristematic cells.
      This effect can be related to changes in the transport and distribution of auxin
      throughout the root. However, similar effects of gravity alteration have been
      found in plant cell cultures in vitro, in which neither specialised structures
      for gravity sensing and signal transduction, nor apparent gravitropism have been
      described. We postulate that gravity resistance, a general mechanism of cellular
      origin for developing rigid structures in plants capable of resisting the gravity
      force, could also be responsible for the changes in cell growth and proliferation
      parameters detected in non-specialised cells. The mechanisms of gravitropism and
      graviresistance are complementary, the first being mostly sensitive to the
      direction of the gravity vector, and the second to its magnitude. At a global
      molecular level, the consequence of gravity alteration is that the genome should
      be finely tuned to counteract a type of stress that plants have never encountered
      before throughout evolution. Multigene families and redundant genes present an
      advantage in that they can experience changes without the risk of being
      deleterious and, for this reason, they should play a key role in the response to
      gravitational stress. 

PMID- 24112665
TI  - Hypercoagulability following blunt solid abdominal organ injury: when to initiate
      anticoagulation.
AB  - BACKGROUND: The optimal time to initiate venous thromboembolism
      pharmacoprophylaxis after blunt abdominal solid organ injury is unknown. METHODS:
      Postinjury coagulation status was characterized using thromboelastography (TEG)
      in trauma patients with blunt abdominal solid organ injuries; TEG was divided
      into 12-hour intervals up to 72 hours. RESULTS: Forty-two of 304 patients (13.8%)
      identified underwent multiple postinjury thromboelastographic studies. Age (P =
      .45), gender (P = .45), and solid organ injury grade (P = .71) were similar
      between TEG and non-TEG patients. TEG patients had higher Injury Severity Scores
      compared with non-TEG patients (33.2 vs 18.3, respectively, P < .01). Among the
      TEG patients, the shear elastic modulus strength and maximum amplitude values
      began in the normal range within the first 12-hour interval after injury,
      increased linearly, and crossed into the hypercoagulable range at 48 hours (15.1
      +/- 1.9 Kd/cs and 57.6 +/- 1.6 mm, respectively; P < .01, analysis of variance).
      CONCLUSIONS: Patients sustaining blunt abdominal solid organ injuries transition
      to a hypercoagulable state approximately 48 hours after injury. In the absence of
      contraindications, pharmacoprophylaxis should be considered before this time for
      effective venous thromboembolism prevention.

PMID- 24112666
TI  - Metastatic lymph node ratio in stage III rectal carcinoma is a valuable
      prognostic factor even with less than 12 lymph nodes retrieved: a prospective
      study.
AB  - BACKGROUND: The aim of this study was to assess the prognostic value of
      metastatic lymph node (LN) ratio (MLNR) in stage III rectal cancer and whether
      this prognostic value remains significant when <12 LNs are retrieved. METHODS:
      This prospective study included 115 patients with stage III rectal cancer from
      2006 to 2010. All patients underwent neoadjuvant long-course chemoradiation,
      curative resection, and postoperative adjuvant therapy (5-fluorouracil and
      leucovorin). Data collected included demographics, tumor pathology, tumor-node
      metastasis staging, number of LNs retrieved, MLNR, recurrence, and mortality.
      RESULTS: The mean number of examined LNs was 12.1, and the mean number of
      metastatic LNs was 3.5 (range, 1 to 19). The mean MLNR was .37 (range, 0 to
      1.00). The mean duration of follow-up was 37 months (range, 24 to 63). Forty
      patients died during the follow-up period (overall mortality, 34.8%), only 31
      because of cancer (cancer-specific mortality, 27%). Univariate analysis revealed
      that ypN stage, lymphovascular invasion, and follow-up duration were
      significantly associated with increased recurrence and decreased survival. Number
      of positive nodes and ypT stage significantly affected recurrence, with no effect
      on overall survival. Multivariate analysis proved that MLNR was the only
      independent risk factor for both mortality and recurrence. Prognostic capability
      was not affected by having <12 nodes retrieved. The best sensitivity and
      specificity of MLNR as a prognostic factor for both tumor recurrence and overall
      survival were achieved at a cutoff value of .375. CONCLUSIONS: MLNR is an
      independent prognostic factor for recurrence and survival after the resection of
      stage III rectal cancer, with high sensitivity and specificity in patients who
      received neoadjuvant chemoradiation and postoperative chemotherapy. The total
      number of LN retrieved did not affect the prognostic value of MLNR even if <12.

PMID- 24112667
TI  - Formal research training during surgical residency: scaffolding for academic
      success.
AB  - BACKGROUND: The purpose of this study was to determine the impact of a formal
      surgical research program (leading to a postgraduate degree) during residency, on
      future research productivity. METHODS: We surveyed all North American graduates
      of the McGill University general surgery residency program between 1987 and 2005.
      The survey included questions on research involvement before, during, and after
      general surgery residency. This was combined with a literature search revealing
      all research publications of the participants. Outcomes were the yearly average
      of publications and awarded funding as faculty members. RESULTS: Seventy-five of
      119 graduates (63%) responded. Staff physicians who had participated in formal
      research programs during residency (n = 35), compared with those who had not (n =
      40), produced more publications per year (2.8 +/- 2.3 vs 1.1 +/- 1.2, P < .01)
      and had greater funding success (81% vs 55%, P = .03). CONCLUSIONS: Residents who
      had participated in formal research programs during residency were more likely to
      have greater academic success.

PMID- 24112668
TI  - Laparoscopic component separation reduces postoperative wound complications but
      does not alter recurrence rates in complex hernia repairs.
AB  - BACKGROUND: The purpose of this study was to evaluate and compare the incidence
      of wound complications after laparoscopic component separation (LCS) vs open
      component separation (OCS) in patients with complex abdominal wall hernias.
      METHODS: A retrospective review was performed of all patients who underwent LCS
      or OCS for repair of a complex abdominal wall hernia at a single institution
      between 2009 and 2011. Charts were reviewed to identify postoperative wound
      complications. A computed tomographic scan or physical examination was used for
      the determination of hernia recurrence. Categoric variables were compared using
      the Fisher exact test. Univariate and multivariate analyses were performed using
      linear and Cox regression. Recurrence rates were compared using log-rank tests
      (Kaplan-Meier method). RESULTS: A total of 44 patients underwent LCS (n = 18) or
      OCS (n = 26). There was no statistically significant difference between categoric
      variables. Multivariate analysis using wound complications as the dependent
      variable showed a statistically significantly lower rate of wound complications
      in the LCS group. CONCLUSIONS: LCS is associated with a lower rate of wound
      complications when compared with OCS but yields comparable recurrence rates.

PMID- 24112669
TI  - Risk factors for umbilical trocar site incisional hernia in laparoscopic
      cholecystectomy: a prospective 3-year follow-up study.
AB  - BACKGROUND: Trocar site incisional hernia (TSIH) is a common complication after
      laparoscopic cholecystectomy. The aim of this study was to evaluate the
      prevalence of TSIH and analyze the influence of several risk factors for this
      complication in a prospective series. METHODS: From 2007 to 2008, a prospective
      observational study with 3 years of follow-up was performed including all
      consecutive patients with cholelithiasis who underwent elective laparoscopic
      cholecystectomy. A multivariate analysis was performed to identify risk factors
      for TSIH. RESULTS: Overall, 241 patients were included. During a median follow-up
      period of 46.8 months, 57 patients (25.9%) were diagnosed with umbilical TSIH by
      physical exam or ultrasound. The multivariate analysis revealed that incision
      enlargement (odds ratio [OR], 14.17; 95% confidence interval [CI], 3.61 to 55.51;
      P < .001), wound infection (OR, 5.62; 95% CI, 2.35 to 13.42; P < .001), diabetes
      mellitus (OR, 2.79; 95% CI, 1.05 to 7.37; P = .0038), and obesity (OR, 2.71; 95%
      CI, 1.28 to 5.75; P = .009) contributed to the risk for developing a TSIH.
      CONCLUSIONS: Umbilical TSIH is highly prevalent. This study identified several
      factors that could be useful to introduce preventive measures in high-risk
      patients.

PMID- 24112671
TI  - Surgical safety checklist and operating room efficiency: results from a large
      multispecialty tertiary care hospital.
AB  - BACKGROUND: The Surgical Safety Checklist (SSC) improves patient safety and
      outcomes; however, barriers to effective use include the perceived negative
      impact on operating room (OR) efficiency. The purpose of this study was to
      determine the effect of SSC implementation on OR efficiency. METHODS: All
      operations at our large multispecialty tertiary care hospital were reviewed for 1
      year pre- and 1-year post-SSC implementation. OR efficiency included operating
      room time, operation time, first starts on time, same-day cancellations, and OR
      disposable cost. RESULTS: A total of 35,570 operations were reviewed: 17,204 pre
      SSC and 18,366 post-SSC. There was no difference between groups for operating
      room time (P = .93), operation time (P = .66), first starts on time (P = .15),
      and same-day cancellations (P = .57). The mean OR disposable cost was
      significantly lower ($70/operation) for the post-SSC group (P < .01).
      CONCLUSIONS: The implementation of an SSC does not negatively impact OR
      efficiency and should not be considered a barrier to effective use. Our data
      suggest that SSC use can reduce overall cost per surgical procedure.

PMID- 24112670
TI  - Use of ketorolac is associated with decreased pneumonia following rib fractures.
AB  - BACKGROUND: The effectiveness of the nonsteroidal anti-inflammatory drug
      ketorolac in reducing pulmonary morbidity after rib fractures remains largely
      unknown. METHODS: A retrospective cohort study was conducted spanning January
      2003 to June 2011 assessing pneumonia within 30 days and potential adverse
      effects of ketorolac among all patients with rib fractures who received ketorolac
      <4 days after injury compared with a random sample of those who did not. RESULTS:
      Among 202 patients who received ketorolac and 417 who did not, ketorolac use was
      associated with decreased pneumonia (odds ratio, .14; 95% confidence interval,
      .04 to .46) and increased ventilator-free days (difference, 1.8 days; 95%
      confidence interval, 1.1 to 2.5) and intensive care unit-free days (difference,
      2.1 days; 95% confidence interval, 1.3 to 3.0) within 30 days. The rates of acute
      kidney injury, gastrointestinal hemorrhage, and fracture nonunion were not
      different. CONCLUSIONS: Early administration of ketorolac to patients with rib
      fractures is associated with a decreased likelihood of pneumonia, without
      apparent risks.

PMID- 24112672
TI  - D-shape asymmetric and symmetric excision with primary closure in the treatment
      of sacrococcygeal pilonidal disease.
AB  - BACKGROUND: Off-midline closure after excision and primary closure in the
      treatment of sacrococcygeal pilonidal disease has been suggested to improve
      surgical outcomes and reduce median recurrence rate. The aim of this study was to
      investigate several features known to be related to recurrence, allowing adequate
      comparison of recurrence between D-shaped asymmetric and symmetric excision in
      the treatment of sacrococcygeal pilonidal disease. METHODS: An analysis of a
      prospectively maintained database of 569 surgical excisions performed for
      sacrococcygeal pilonidal disease between 1988 and 2007 was performed. RESULTS:
      The recurrence rate was lower in the asymmetric (n = 423) than in the symmetric
      (n = 101) group (9% vs 22.0%, P = .0001). After a median follow-up period of 11
      years, 5-year 10-year, and 20-year disease-free survival rates were higher in the
      asymmetric group (94%, 92%, and 89% vs 84%, 79%, and 71%, respectively, P =
      .005). CONCLUSIONS: D-shaped asymmetric excision is an effective treatment of
      sacrococcygeal pilonidal sinus. Better long-term recurrence rates are achieved
      compared with symmetric excision, when stratified for several features known to
      be related to recurrence.

PMID- 24112673
TI  - Perioperative indicators of hypocalcemia in total thyroidectomy: the role of
      vitamin D and parathyroid hormone.
AB  - BACKGROUND: Hypocalcemia is a common complication of thyroidectomy. The aim of
      this study was to identify risk factors for this problem. METHODS: This
      prospective analysis included 111 patients undergoing total or completion
      thyroidectomy. Preoperative vitamin D levels and postoperative day 1 parathyroid
      hormone levels were analyzed for their predictive effects on postoperative
      hypocalcemia. RESULTS: Patients with ionized calcium <4.4 mg/dL had significantly
      lower mean parathyroid hormone levels than normocalcemic patients (13.0 vs 28.4
      pg/mL, P < .001). Parathyroid hormone levels were also significantly lower in
      symptomatic patients (11.0 vs 28.4 pg/mL, P < .001). Preoperative vitamin D
      level, body mass index, gender, and pathologic findings were not associated with
      low calcium levels or symptoms of hypocalcemia. CONCLUSIONS: Younger age and low
      postoperative parathyroid hormone levels are predictive of symptomatic
      hypocalcemia. A parathyroid hormone level outside of the reference range may
      indicate a need for more aggressive postoperative calcium supplementation and
      treatment with activated vitamin D. Older patients with normal postoperative
      parathyroid hormone levels may be safely discharged with appropriate calcium
      supplementation.

PMID- 24112674
TI  - Tumor growth pattern as predictor of colorectal liver metastasis recurrence.
AB  - BACKGROUND: Surgical resection is the gold standard therapy for the treatment of
      colorectal liver metastases (CRM). The aim of this study was to investigate the
      impact of tumor growth patterns on disease recurrence. METHODS: We enrolled 91
      patients who underwent CRM resection. Pathological specimens were prospectively
      evaluated, with particular attention given to tumor growth patterns (infiltrative
      vs pushing). RESULTS: Tumor recurrence was observed in 65 patients (71.4%).
      According to multivariate analysis, 3 or more lesions (P = .05) and the
      infiltrative tumor margin type (P = .05) were unique independent risk factors for
      recurrence. Patients with infiltrative margins had a 5-year disease-free survival
      rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P =
      .05). CONCLUSIONS: CRM patients with pushing margins presented superior disease
      free survival rates compared with patients with infiltrative margins. Thus, the
      adoption of the margin pattern can represent a tool for improved selection of
      patients for adjuvant treatment.

PMID- 24112675
TI  - Emergent cholecystostomy is superior to open cholecystectomy in extremely ill
      patients with acalculous cholecystitis: a large multicenter outcome study.
AB  - BACKGROUND: Morbidity and mortality are very high for critically ill patients who
      develop acute acalculous cholecystitis (AAC). The aim of this study was to
      compare outcomes in extremely ill patients with AAC treated with percutaneous
      cholecystostomy (PC), laparoscopic cholecystectomy (LC), or open cholecystectomy
      (OC), which were also analyzed together in the LC-plus-OC (LO) group. METHODS:
      Discharge data from the University HealthSystem Consortium database were accessed
      using International Classification of Diseases codes. The University HealthSystem
      Consortium's Clinical Data Base/Resource Manager allows member hospitals to
      compare patient-level, risk-adjusted outcomes. Multivariate regression models for
      extremely ill patients undergoing PC or LO for the diagnosis of AAC were created
      and analyzed. RESULTS: A total of 1,725 extremely ill patients were diagnosed
      with AAC between October 2007 and June 2011. Patients undergoing PC (n = 704)
      compared with the LO group (n = 1,021) showed decreased morbidity (5.0% with PC
      vs 8.0% with LO, P < .05), fewer intensive care unit admissions (28.1% with PC vs
      34.6% with LO, P < .05), decreased length of stay (7 days with PC vs 8 days with
      LO, P < .05), and lower costs ($40,516 with PC vs $53,011 with LO, P < .05).
      Although perioperative outcomes of PC compared with LC were statistically
      similar, PC had lower costs compared with LC ($40,516 vs 51,596, P < .005).
      Multivariate regression analysis showed that LC (n = 822), compared with OC (n =
      199), had lower mortality (odds ratio [OR], .3; 95% confidence interval [CI], .1
      to .6), lower morbidity (OR, .4; 95% CI, .2 to .7), reduced intensive care unit
      admission (OR, .3; 95% CI, .2 to .5), and similar 30-day readmission rates (OR,
      1.0; 95% CI, .6 to 1.5). Also, decreased length of stay (7 days with LC vs 8 days
      with OC) and costs ($51,596 with LC vs $61,407 with OC) were observed, with a 26%
      conversion rate to an open procedure. CONCLUSIONS: On the basis of this
      experience, extremely ill patients with AAC have superior outcomes with PC. LC
      should be performed in patients in whom the risk for conversion is low and in
      whom medical conditions allow. These results show PC to be a safe and cost
      effective bridge treatment strategy with perioperative outcomes superior to those
      of OC.

PMID- 24112676
TI  - Laparoscopic versus open repair of perforated gastroduodenal ulcer: a National
      Surgical Quality Improvement Program analysis.
AB  - BACKGROUND: Surgical repair of perforated gastroduodenal ulcers remains a common
      indication for emergent surgery. The aim of this study was to test the hypothesis
      that the laparoscopic approach (LA) would be associated with reduced length of
      stay compared to the open approach. METHODS: Patients with acute, perforated
      gastroduodenal ulcer were identified in the National Surgical Quality Improvement
      Program database, of whom 50 had the LA. One-to-one case/control matching on the
      basis of age, American Society of Anesthesiologists class, gender, and cardiac
      disease was evaluated for outcome analysis. RESULTS: After matching, the 2 groups
      had similar characteristics. The rates of wound complications, organ space
      infections, prolonged ventilation, postoperative sepsis, return to the operating
      room, and mortality tended to be lower for the LA, although not significantly.
      Length of hospital stay was, however, significantly shorter for the LA by an
      average of 5.4 days. CONCLUSIONS: The LA appears to be safe in mild to moderately
      ill patients with perforated peptic ulcer disease and is associated with reduced
      use of hospital resources.

PMID- 24112677
TI  - Upgrade of high-risk breast lesions detected on mammography in the Breast Cancer
      Surveillance Consortium.
AB  - BACKGROUND: Upgrade rates of high-risk breast lesions after screening mammography
      were examined. METHODS: The Breast Cancer Surveillance Consortium registry was
      used to identify all Breast Imaging Reporting and Data System category 4
      assessments followed by needle biopsies with high-risk lesions. Follow-up was
      performed for all women. RESULTS: High-risk lesions were found in 957 needle
      biopsies, with excision documented in 53%. Most (n = 685) were atypical ductal
      hyperplasia (ADH), 173 were lobular neoplasia, and 99 were papillary lesions.
      Upgrade to cancer varied with type of lesion (18% in ADH, 10% in lobular
      neoplasia, and 2% in papillary lesions). In premenopausal women with ADH, upgrade
      was associated with family history. Cancers associated with ADH were mostly (82%)
      ductal carcinoma in situ, and those associated with lobular neoplasia were mostly
      (56%) invasive. During a further 2 years of follow-up, cancer was documented in
      1% of women with follow-up surgery and in 3% with no surgery. CONCLUSIONS:
      Despite low rates of surgery, low rates of cancer were documented during follow
      up. Benign papillary lesions diagnosed on Breast Imaging Reporting and Data
      System category 4 mammograms among asymptomatic women do not justify surgical
      excision.

PMID- 24112678
TI  - Peritumoral deposits as an adverse prognostic indicator of colorectal cancer.
AB  - BACKGROUND: The aim of this study was to determine the prognostic value of
      peritumoral deposits (PTDs) in colorectal cancer (CRC). METHODS: A total of 695
      patients with pT3/T4 CRC (1980 to 1999) were reviewed. Tumor deposits located >=2
      mm from the front of the direct spread in the primary tumor were evaluated as
      PTDs. RESULTS: PTDs were observed in 111 patients (16.0%). The incidence of PTDs
      increased according to increasing N stage: 7% for N0, 22% for N1, and 39% for N2
      (P < .0001). Five-year disease-specific survival was 85.0% in patients without
      PTDs and 59.5% in those with PTDs (P < .0001). Multivariate analysis showed that
      PTDs affected disease-specific survival independent of T and N stages. A
      significant prognostic impact of PTDs was similarly observed in another cohort
      comprising 474 patients with pT3/T4 CRC (2000 to 2005). The kappa values among 8
      observers were .70 for PTDs and .32 for the conventional growth pattern.
      CONCLUSIONS: PTDs have considerable prognostic relevance and offer improved
      judgment reproducibility in assessing the invasive margin of CRC.

PMID- 24112679
TI  - Anatomic resection reduces the recurrence of solitary hepatocellular carcinoma
      <=5 cm without macrovascular invasion.
AB  - BACKGROUND: In patients with solitary hepatocellular carcinoma <=5 cm without
      macrovascular invasion, it is unknown whether the initial anatomic resection
      improves the long-term survival. METHODS: Among 545 initial hepatectomies for
      hepatocellular carcinoma between 2000 and 2012, the 233 patients with the
      aforementioned criteria of hepatocellular carcinoma were enrolled. RESULTS: The
      mean observation time was 1,125 days. Disease-free 5-year survival rates with and
      without anatomic resection were 46% and 23%, respectively (P = .009).
      Multivariate analyses for disease-free survival rates revealed the risk factors
      to be alpha-fetoprotein (odds ratio, 1.6; P = .028) and anatomic resection (odds
      ratio, .7; P = .048), while increased Child-Pugh score (>5) was the only
      independent risk factor for overall survival (odds ratio, 1.8; P = .043). The 5
      year overall survival rates with and without Child-Pugh score 5 were 74% and 40%,
      respectively (P < .0001, log-rank test). CONCLUSIONS: Initial anatomic resection
      for small solitary hepatocellular carcinoma without macrovascular invasion
      improved disease-free survival rates remarkably.

PMID- 24112680
TI  - Feasibility of breast conserving surgery in multifocal breast cancers.
AB  - BACKGROUND: Multifocal breast cancers (MFBCs) present a challenge to surgeons.
      Although its feasibility is still controversial, breast-conserving surgery (BCS)
      is not contraindicated for MFBCs. The investigators retrospectively evaluated the
      feasibility of BCS and reviewed histopathologic findings in patients with MFBC.
      METHODS: A total of 222 patients with MFBC who were treated with either BCS (119
      patients) or mastectomy (103 patients) at a single institution between January
      2002 and December 2011 were retrospectively evaluated. RESULTS: The median follow
      up time was 55 months (range, 10 to 102 months). Lymphovascular invasion and
      lymph node involvement were significantly less frequent in the BCS group (48.8%
      vs 62.2% for lymphovascular invasion, P = .04; 52.1% vs 71.8% for lymph node
      involvement, P = .002). There were no differences in local recurrence rates
      between the 2 groups. The overall survival rates were 92% in the BCS group and
      72% in the mastectomy group (P = .000). CONCLUSIONS: BCS is a feasible and safe
      procedure for the removal of multifocal tumors. Extended lymphovascular invasion
      is associated with mortality in patients who undergo mastectomy.

PMID- 24112681
TI  - The evolution in management of patients with subcentimeter, node-negative, triple
      negative breast cancer.
AB  - BACKGROUND: The aim of this study was to determine the evolution in treatment
      recommendations and outcomes for patients with subcentimeter, node-negative,
      triple-negative disease. METHODS: Patients were divided into a remote (diagnosed
      from 1997 to 2003) and a recent (diagnosed from 2004 to 2011) group.
      Demographics, tumor size, surgical treatment, use of adjuvant chemotherapy,
      survival, and disease recurrence were evaluated. RESULTS: Thirty patients were
      placed in the remote group and 31 in the recent group. Demographics, tumor sizes,
      and surgical treatment were similar between groups. The use of adjuvant
      chemotherapy increased from 7% to 42% in the recent group (P < .002). Disease
      free survival and recurrence (7%) was not influenced by the use of chemotherapy.
      CONCLUSIONS: This study demonstrates that adjuvant chemotherapy is increasingly
      used in patients with the triple-negative phenotype, regardless of other
      favorable prognostic variables. The value of adjuvant chemotherapy for the
      subgroup of patients in our study is unclear and mandates further investigation.

PMID- 24112682
TI  - Semi-urgent surgery in hospitalized patients with severe ulcerative colitis does
      not increase overall J-pouch complications.
AB  - BACKGROUND: Surgeons frequently discourage patients with ulcerative colitis from
      having surgery in the midst of an acute flare for fear of complications and poor
      long-term outcomes. METHODS: Outcomes of patients undergoing urgent versus
      elective surgery for ulcerative colitis were compared via retrospective review.
      RESULTS: Patients undergoing urgent (n = 80) versus elective (n = 99) surgery
      were younger, were more malnourished, had more severe active disease, and had
      higher steroid use (P <= .05). During surgery, hemodynamic stability was similar,
      but urgent patients underwent more subtotal colectomies (5.1% vs 29%, P < .0001)
      and fewer laparoscopic procedures (8.8% vs 18%, P = .07). Multivariate regression
      suggested that short-term complications were increased with higher body mass
      index and urgency status (P <= .05). Anastomotic leaks and long-term
      complications were similar between groups. Surgeon inexperience and use of
      immunomodulators other than infliximab were associated with increased odds of
      long-term fistula/abscess (odds ratio, 5.56; P = .05] and pouch failure (odds
      ratio, 13.3; P = .01). CONCLUSIONS: Surgery in patients with acute ulcerative
      colitis flares is associated with more short-term complications than elective
      procedures but does not appear to affect risk for anastomotic leak or long-term
      complications when performed by an expert.

PMID- 24112683
TI  - Neuroprotective effects of progesterone in traumatic brain injury: blunted in
      vivo neutrophil activation at the blood-brain barrier.
AB  - BACKGROUND: Progesterone (PRO) may confer a survival advantage in traumatic brain
      injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema
      by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the
      blood-brain barrier (BBB). METHODS: CD1 mice received repeated PRO (16 mg/kg
      intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals
      underwent craniotomy without TBI. The modified Neurological Severity Score graded
      neurologic recovery. A second craniotomy allowed in vivo observation of pial
      EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed
      cerebral edema. RESULTS: Compared with the vehicle, PRO reduced subjective
      cerebral swelling (2.9 +/- .1 vs 1.2 +/- .1, P < .001), PMN rolling (95 +/- 1.8
      vs 57 +/- 2.0 cells/100 MUm/min, P < .001), total EC/PMN adhesion (2.0 +/- .4 vs
      .8 +/- .1 PMN/100 MUm, P < .01), and vascular permeability (51.8% +/- 4.9% vs
      27.1% +/- 4.6%, P < .01). TBI groups had similar a Neurological Severity Score
      and cerebral wet/dry ratios (P > .05). CONCLUSIONS: PRO reduces live
      pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO
      effects on the microcirculation warrant further investigation.

PMID- 24112684
TI  - Microbial community structure and functioning in marine sediments associated with
      diffuse hydrothermal venting assessed by integrated meta-omics.
AB  - Deep-sea hydrothermal vents are unique environments on Earth, as they host
      chemosynthetic ecosystems fuelled by geochemical energy with
      chemolithoautotrophic microorganisms at the basis of the food webs. Whereas
      discrete high-temperature venting systems have been studied extensively, the
      microbiotas associated with low-temperature diffuse venting are not well
      understood. We analysed the structure and functioning of microbial communities in
      two diffuse venting sediments from the Jan Mayen vent fields in the Norwegian
      Greenland Sea, applying an integrated 'omics' approach combining
      metatranscriptomics, metaproteomics and metagenomics. Polymerase chain reaction
      independent three-domain community profiling showed that the two sediments hosted
      highly similar communities dominated by Epsilonproteobacteria,
      Deltaproteobacteria and Gammaproteobacteria, besides ciliates, nematodes and
      various archaeal taxa. Active metabolic pathways were identified through
      transcripts and peptides, with genes of sulphur and methane oxidation, and carbon
      fixation pathways highly expressed, in addition to genes of aerobic and anaerobic
      (nitrate and sulphate) respiratory chains. High expression of chemotaxis and
      flagella genes reflected a lifestyle in a dynamic habitat rich in physico
      chemical gradients. The major metabolic pathways could be assigned to distinct
      taxonomic groups, thus enabling hypotheses about the function of the different
      prokaryotic and eukaryotic taxa. This study advances our understanding of the
      functioning of microbial communities in diffuse hydrothermal venting sediments. 

PMID- 24112685
TI  - Cardiac channelopathies associated with infantile fatal ventricular arrhythmias:
      from the cradle to the bench.
AB  - BACKGROUND: Fatal ventricular arrhythmias in the early period of life have been
      associated with cardiac channelopathies for decades, and postmortem analyses in
      SIDS victims have provided evidence of this association. However, the prevalence
      and functional properties of cardiac ion channel mutations in infantile fatal
      arrhythmia cases are not clear. METHODS AND RESULTS: Seven infants with
      potentially lethal arrhythmias at age < 1 year (5 males, age of onset 44.1 +/-
      72.1 days) were genetically analyzed for KCNQ1, KCNH2, KCNE1-5, KCNJ2, SCN5A,
      GJA5, and CALM1 by using denaturing high-performance liquid chromatography and
      direct sequencing. Whole-cell currents of wildtype and mutant channels were
      recorded and analyzed in Chinese hamster ovary cells transfected with SCN5A and
      KCNH2 cDNA. In 5 of 7 patients, we identified 4 mutations (p.N1774D, p.T290fsX53,
      p.F1486del and p.N406K) in SCN5A, and 1 mutation (p.G628D) in KCNH2. N1774D,
      F1486del, and N406K in SCN5A displayed tetrodotoxin-sensitive persistent late
      Na(+) currents. By contrast, SCN5A-T290fsX53 was nonfunctional. KCNH2-G628D
      exhibited loss of channel function. CONCLUSION: Genetic screening of 7 patients
      was used to demonstrate the high prevalence of cardiac channelopathies.
      Functional assays revealed both gain and loss of channel function in SCN5A
      mutations, as well as loss of function associated with the KCNH2 mutation.

PMID- 24112686
TI  - Antibacterial mechanisms identified through structural systems pharmacology.
AB  - BACKGROUND: The growing discipline of structural systems pharmacology is applied
      prospectively in this study to predict pharmacological outcomes of antibacterial
      compounds in Escherichia coli K12. This work builds upon previously established
      methods for structural prediction of ligand binding pockets on protein molecules
      and utilizes and expands upon the previously developed genome scale model of
      metabolism integrated with protein structures (GEM-PRO) for E. coli, structurally
      accounting for protein complexes. Carefully selected case studies are
      demonstrated to display the potential for this structural systems pharmacology
      framework in discovery and development of antibacterial compounds. RESULTS: The
      prediction framework for antibacterial activity of compounds was validated for a
      control set of well-studied compounds, recapitulating experimentally-determined
      protein binding interactions and deleterious growth phenotypes resulting from
      these interactions. The antibacterial activity of fosfomycin, sulfathiazole, and
      trimethoprim were accurately predicted, and as a negative control glucose was
      found to have no predicted antibacterial activity. Previously uncharacterized
      mechanisms of action were predicted for compounds with known antibacterial
      properties, including (1-hydroxyheptane-1,1-diyl)bis(phosphonic acid) and
      cholesteryl oleate. Five candidate inhibitors were predicted for a desirable
      target protein without any known inhibitors, tryptophan synthase beta subunit
      (TrpB). In addition to the predictions presented, this effort also included
      significant expansion of the previously developed GEM-PRO to account for
      physiological assemblies of protein complex structures with activities included
      in the E. coli K12 metabolic network. CONCLUSIONS: The structural systems
      pharmacology framework presented in this study was shown to be effective in the
      prediction of molecular mechanisms of antibacterial compounds. The study provides
      a promising proof of principle for such an approach to antibacterial development
      and raises specific molecular and systemic hypotheses about antibacterials that
      are amenable to experimental testing. This framework, and perhaps also the
      specific predictions of antibacterials, is extensible to developing antibacterial
      treatments for pathogenic E. coli and other bacterial pathogens.

PMID- 24112687
TI  - Comparison of ultrasound and magnetic resonance imaging for diagnosis and follow
      up of joint lesions in patients with haemophilia.
AB  - Haematomas and recurrent haemarthroses are a common problem in haemophilia
      patients from early age. Early diagnosis is critical in preventing haemophilic
      arthritis, and recent years have seen excellent advances in musculoskeletal
      ultrasound as a diagnostic tool in soft tissue lesions. In this study, we
      compared the results of ultrasound imaging for the diagnosis of musculoskeletal
      injuries in haemophilia patients with scores obtained using magnetic resonance
      (MRI) scans. A total of 61 haemophilia patients aged 4-82 years were included in
      this study. Both knees and ankles of each patient were assessed using the Gilbert
      (clinical assessment) and Pettersson scores (X-ray assessment). Patients with
      severe haemophilia (n = 30) were examined using ultrasound and MRI (Denver
      scoring system). Results obtained with ultrasound and MRI in severe patients were
      correlated using the Pearson test. In patients with severe haemophilia, normal
      joints were similarly assessed with MRI and ultrasound (kappa = 1.000). By
      component of joint assessment, haemarthrosis was similarly diagnosed with both
      techniques in all joints (kappa = 1.000). A good positive correlation was found
      between these techniques in detecting and locating synovial hyperplasia (kappa =
      0.839-1.000, knees and ankles respectively), and erosion of margins (kappa =
      0.850-1.000). The presence of bone cysts or cartilage loss was better detected
      with MRI (kappa = 0.643-0.552 for knees and ankles, and kappa = 0.643-0.462
      respectively). Ultrasound is useful in detecting joint bleeds, synovial
      hyperplasia and joint erosions, with results comparable to those of MRI. A quick
      and affordable technique, ultrasound imaging may be useful for monitoring joint
      bleeds and structure normalization and maintenance in routine practice.

PMID- 24112688
TI  - Synthetic substrates specific to activated plasmin can monitor the enzymatic
      functional status in situ in breast cancer cells.
AB  - We here strove to overcome the limitations of expression analyses such as PCR and
      IHC, based on molecular recognition between target and probe molecules, by
      designing synthetic substrates specific to the target molecules to directly
      estimate the enzymatic functionality in situ. The specific substrate contains a
      probing unit, which is an organic fragment for specific enzyme binding, and a
      reactive unit, which is a natural peptide subject to catalysis. In this study,
      the activation of plasminogen to plasmin was examined in MDA-MB231 breast cancer
      cells using the plasmin-specific synthetic substrates designed from their
      inhibitors. The localization and function of the activated plasmin were
      successfully visualized by fluorophore combined with the specific substrate
      concurrently. This would be the first time for activated plasmin at work in situ
      by direct observation. Our concept to directly monitor the functionality of
      target enzymes can be used straightforwardly for other proteases such as
      cathepsins or caspases. Also, this substrate concept as a 'tailor-made substrate'
      would be utilized as a novel functional molecular probe in vivo with appropriate
      detectable probes. 

PMID- 24112689
TI  - Malaria vaccine research and development: the role of the WHO MALVAC committee.
AB  - The WHO Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on
      strategic priorities, activities and technical issues related to global efforts
      to develop vaccines against malaria. MALVAC convened a series of meetings to
      obtain expert, impartial consensus views on the priorities and best practice for
      vaccine-related research and development strategies. The technical areas covered
      during these consultations included: guidance on clinical trial design for
      candidate sporozoite and asexual blood stage vaccines; measures of efficacy of
      malaria vaccines in Phase IIb and Phase III trials; standardization of
      immunoassays; the challenges of developing assays and designing trials for
      interventions against malaria transmission; modelling impact of anti-malarial
      interventions; whole organism malaria vaccines, and Plasmodium vivax vaccine
      related research and evaluation. These informed discussions and opinions are
      summarized here to provide guidance on harmonization of strategies to help ensure
      high standards of practice and comparability between centres and the outcome of
      vaccine trials. 

PMID- 24112691
TI  - Evaluation of hair loss in cats occurring after treatment with a topical flea
      control product.
AB  - BACKGROUND: A formulation containing 39.6% spinetoram resulted in a higher than
      anticipated number of reports of alopecia at the site of application in the first
      months following commercial product launch. HYPOTHESIS/OBJECTIVES: To determine
      the cause of the alopecia using histopathology, including assessment for
      inflammation, follicular findings of physical trauma (plucking/pulling behaviour)
      and changes in follicular cycling. ANIMALS: Twenty-four flea-free, male and
      female adult domestic short hair cats within a private research colony. METHODS:
      Cats were treated with a single application of 39.6% spinetoram on day 0;
      personnel were not blinded. Observations of the skin and hair coat began
      immediately and were repeated at 30 min and 1, 2, 3, 4, 6, 8 and 12 h post
      application and then on subsequent days at the same time as initial dosing and at
      2, 4, 6, 8 and 12 h after that time, until day 5. If hair thinning or loss was
      observed, a skin biopsy sample was collected. Two cats not exhibiting
      abnormalities were biopsied on day 6. RESULTS: Thirty-eight per cent of cats
      (nine of 24) developed hair thinning and alopecia of sufficient severity within
      78 h post-application of the product to warrant skin biopsy. Abnormalities in the
      skin were limited to the application site and were consistent with physical
      trauma (pulling or plucking) to the hair. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Microscopic changes in the hair follicles of affected cats were consistent with
      self-induced trauma or barbering behaviour. All changes were reversible and
      paralleled findings associated with well-established, topical flea control
      products.

PMID- 24112692
TI  - Treatment of inflammatory linear verrucous epidermal nevus with 2940 nm erbium
      fractional laser.

PMID- 24112694
TI  - Mitigating the effect of development on bats in England with derogation
      licensing.
AB  - The Convention on Biological Diversity has catalyzed worldwide awareness of
      threats to biological diversity and stimulated global conservation strategies.
      These have led to national and international legislation and have generated
      debate about the most effective conservation actions. Under the EU Habitats
      Directive, all member states are obliged to establish a system for strict
      protection of species listed in Annex IV(a), which includes all bats. In England,
      this obligation has resulted in legislation that allows for derogation from
      strict protection under license, provided activities are undertaken to mitigate
      any potential negative effects on bat numbers. We used an evidence-based approach
      to assess the cost-effectiveness of mitigation strategies and the English bat
      derogation licensing process as a whole. We analyzed data from 389 bat derogation
      licenses issued in England from 2003 to 2005 relating to 1776 roosts and 15
      species to determine the nature and extent of development and mitigation
      activities and their effects on bats. Overall the effects of licensed activities
      on roosts were negative. Despite the level of protection afforded to bats, the
      majority (68%) of roosts for which derogation licenses were issued were
      destroyed. There were species-specific differences in the probability of roosts
      being destroyed, and impacts on roosts did not reflect a species' conservation
      status. Information provided by licensees was inadequate and inconsistent. Most
      licensees (67%) failed to submit postdevelopment reports, and postdevelopment
      monitoring was conducted at only 19% of sites. Despite a minimum of L4.13 million
      spent on mitigation structures for bats from 2003 to 2005, it was unclear whether
      the licensing process meets EU obligations. On the basis of our results, we
      believe there is a need to overhaul the licensing process, to establish a
      comprehensive, standardized postdevelopment monitoring system, and to demonstrate
      that mitigation is commensurate with Britain's legal obligations. Mitigando el
      Efecto del Desarrollo sobre los Murcielagos en Inglaterra con Licencias de
      Derogacion. 

PMID- 24112693
TI  - Exogenous surfactant therapy in 2013: what is next? Who, when and how should we
      treat newborn infants in the future?
AB  - BACKGROUND: Surfactant therapy is one of the few treatments that have
      dramatically changed clinical practice in neonatology. In addition to respiratory
      distress syndrome (RDS), surfactant deficiency is observed in many other clinical
      situations in term and preterm infants, raising several questions regarding the
      use of surfactant therapy. OBJECTIVES: This review focuses on several points of
      interest, including some controversial or confusing topics being faced by
      clinicians together with emerging or innovative concepts and techniques,
      according to the state of the art and the published literature as of 2013.
      Surfactant therapy has primarily focused on RDS in the preterm newborn. However,
      whether this treatment would be of benefit to a more heterogeneous population of
      infants with lung diseases other than RDS needs to be determined. Early trials
      have highlighted the benefits of prophylactic surfactant administration to
      newborns judged to be at risk of developing RDS. In preterm newborns that have
      undergone prenatal lung maturation with steroids and early treatment with
      continuous positive airway pressure (CPAP), the criteria for surfactant
      administration, including the optimal time and the severity of RDS, are still
      under discussion. Tracheal intubation is no longer systematically done for
      surfactant administration to newborns. Alternative modes of surfactant
      administration, including minimally-invasive and aerosolized delivery, could thus
      allow this treatment to be used in cases of RDS in unstable preterm newborns, in
      whom the tracheal intubation procedure still poses an ethical and medical
      challenge. CONCLUSION: The optimization of the uses and methods of surfactant
      administration will be one of the most important challenges in neonatal intensive
      care in the years to come.

PMID- 24112695
TI  - Acute irritant threshold correlates with barrier function, skin hydration and
      contact hypersensitivity in atopic dermatitis and rosacea.
AB  - The aim of the study was to disclose interactions between epidermal barrier, skin
      irritation and sensitization in healthy and diseased skin. Transepidermal water
      loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients
      with atopic dermatitis (AD), rosacea and healthy controls. A 4-h patch test with
      seven concentrations of sodium lauryl sulphate was performed to determine the
      irritant threshold (IT). Contact sensitization pattern was revealed by patch
      testing with European baseline series. Subjects with a lower IT had higher TEWL
      values and lower SCH. Subjects with positive allergic reactions had significantly
      lower IT. In AD, epidermal barrier deterioration was detected on both volar
      forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters
      were observed on the facial skin only, suggesting that barrier impediment is
      restricted to the face in rosacea, in contrast with AD where the abnormal skin
      physiology is generalized. 

PMID- 24112696
TI  - Quantifying relationships between rooting traits and water uptake under drought
      in Mediterranean barley and durum wheat.
AB  - In Mediterranean regions drought is the major factor limiting spring barley and
      durum wheat grain yields. This study aimed to compare spring barley and durum
      wheat root and shoot responses to drought and quantify relationships between root
      traits and water uptake under terminal drought. One spring barley (Hordeum
      vulgare L. cv. Rum) and two durum wheat Mediterranean cultivars (Triticum
      turgidum L. var durum cvs Hourani and Karim) were examined in soil-column
      experiments under well watered and drought conditions. Root system architecture
      traits, water uptake, and plant growth were measured. Barley aerial biomass and
      grain yields were higher than for durum wheat cultivars in well watered
      conditions. Drought decreased grain yield more for barley (47%) than durum wheat
      (30%, Hourani). Root-to-shoot dry matter ratio increased for durum wheat under
      drought but not for barley, and root weight increased for wheat in response to
      drought but decreased for barley. The critical root length density (RLD) and root
      volume density (RVD) for 90% available water capture for wheat were similar to
      (cv. Hourani) or lower than (cv. Karim) for barley depending on wheat cultivar.
      For both species, RVD accounted for a slightly higher proportion of phenotypic
      variation in water uptake under drought than RLD. 

PMID- 24112697
TI  - MIB-1 labeling index as a prognostic factor for patients with follicular lymphoma
      treated with rituximab plus CHOP therapy.
AB  - The MIB-1 labeling index, which is based on Ki67 immunostaining, is widely used
      to evaluate the proliferation of tumor cells in lymphoma. However, its clinical
      significance has not been fully assessed. We retrospectively evaluated the
      prognostic impact of the MIB-1 labeling index at the time of diagnosis, in 98
      patients with follicular lymphoma (FL) grade 1-3b who were treated uniformly with
      rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R
      CHOP) therapy. The 5-year progression-free survival (PFS) for an MIB-1 labeling
      index of >=10% (n = 60) and <10% (n = 38) was 35% and 61%, respectively (P =
      0.015). The 5-year overall survival (OS) for an MIB-1 labeling index of >=10% and
      <10% was 77% and 92%, respectively (P = 0.025). Pathological grading was not
      correlated with PFS or OS. In multivariate analysis, an MIB-1 labeling index of
      >=10% was independently associated with poor PFS and OS. In conclusion, an MIB-1
      labeling index of 10% is a useful cut-off level for predicting the prognosis of
      patients with FL.

PMID- 24112698
TI  - Epidermal pigmentation in the human lineage is an adaptation to ultraviolet
      radiation.

PMID- 24112699
TI  - Identification of dichloroacetic acid degrading Cupriavidus bacteria in a
      drinking water distribution network model.
AB  - AIMS: Bacterial community structure and composition of a drinking water network
      were assessed to better understand this ecosystem in relation to haloacetic acid
      (HAA) degradation and to identify new bacterial species having HAA degradation
      capacities. METHODS AND RESULTS: Biofilm samples were collected from a model
      system, simulating the end of the drinking water distribution network and
      supplied with different concentrations of dichloroacetic and trichloroacetic
      acids at different periods over the course of a year. The samples were analysed
      by culturing, denaturing gradient gel electrophoresis (DGGE) and sequencing. Pipe
      diameter and HAA ratios did not impact the bacterial community profiles, but the
      season had a clear influence. Based on DGGE profiles, it appeared that a
      particular biomass has developed during the summer compared with the other
      seasons. Among the bacteria isolated in this study, those from genus Cupriavidus
      were able to degrade dichloroacetic acid. Moreover, these bacteria degrade
      dichloroacetic acid at 18 degrees C but not at 10 degrees C. CONCLUSIONS: The
      microbial diversity evolved throughout the experiment, but the bacterial
      community was distinct during the summer. Results obtained on the capacity of
      Cupriavidus to degrade DCAA only at 18 degrees C but not at 10 degrees C indicate
      that water temperature is a major element affecting DCAA degradation and
      confirming observations made regarding season influence on HAA degradation in the
      drinking water distribution network. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      is the first demonstration of the HAA biodegradation capacity of the genus
      Cupriavidus.

PMID- 24112700
TI  - Acute total hip replacement for acetabular fractures: a systematic review of the
      literature.
AB  - INTRODUCTION: Immediate total hip replacement (THR) in patients with acetabular
      fractures is controversial because of concerns about high complication rates. The
      current article is a systematic review of the literature on the use of acute THR
      for the treatment of acetabular fractures. MATERIALS AND METHODS: This systematic
      review included studies published in English between 1992 and 2012 of subjects
      with acetabular fracture undergoing immediate THR. Outcomes of interest included
      indications; clinical assessment, including walking ability; comparison with
      control group; associated procedures, and rate of complications, such as
      loosening or revision surgery. RESULTS: This review identified six studies, of
      which only one included a control group. Acute THR was associated with satisfying
      outcomes with regard to clinical assessment and walking ability. The comparative
      study assessed the difference between acute THR and delayed THR in acetabular
      fractures: improved outcomes were observed in the delayed THR group, although the
      differences between the two groups were not statistically significant.
      DISCUSSION: According to data reported in the literature, acute primary THR can
      be successful in patients with poor bone quality, combined acetabular and femoral
      neck fractures, or pathological fractures and concurrent osteoarthritis of the
      hip. Relative indications include old age, delayed presentation, substantial
      medical comorbidities, and pathologic obesity. Clinical outcomes with acute THR
      were similar to those with delayed THR. Although the results reported in the six
      studies reviewed here were satisfying overall, there is limited evidence in this
      area in the existing literature and future prospective investigations are
      required. CONCLUSION: Data reported in the literature indicate that immediate THR
      can be successful in appropriately selected elderly patients or patients with
      extensive osteoporosis, combined acetabular and femoral neck fractures or
      pathological fractures. There is currently a limited evidence base for THR in
      patients with acetabular fractures; therefore, physicians' practice and expertise
      are the most useful tools in clinical practice.

PMID- 24112701
TI  - Radial head, radiocapitellar and total elbow arthroplasties: a review of recent
      literature.
AB  - The outcome of prosthetic elbow surgery is continually evolving. We thoroughly
      reviewed the literature on this issue to analyse the indications, outcomes and
      complications of the numerous types of implants currently in use. Radial head
      replacement is recommended in comminuted fractures of the radial head and in post
      traumatic conditions. Medium- and long-term results prove to be satisfactory in
      the majority of cases, with no evidence to indicate that some prostheses
      (monopolar vs. bipolar; cemented vs. press-fit) are more effective than others;
      nonetheless, the bipolar-cemented implant was found to be associated with a lower
      revision rate than other prostheses. Unicompartmental arthroplasty has recently
      been used for the treatment of osteoarthritis and rheumatoid arthritis when the
      lateral compartment is prevalently involved; the results reported to date have
      been encouraging, although further studies are warranted to confirm the validity
      of these implants. Total elbow arthroplasty is performed in a range of
      conditions, including distal humerus fractures in the elderly and elbow
      arthritis. In the former condition, linked elbow replacement yields excellent
      results with few complications and a low revision rate. In elbow arthritis, total
      elbow arthroplasty is indicated when patients suffer from disabling pain,
      stiffness and/or instability that prevent them from performing daily activities.
      Unlinked elbow arthroplasty, which is used above all in rheumatoid arthritis,
      also yields satisfactory results, although the risk of instability persists. The
      use of linked elbow arthroplasty, which yields similar results but lower revision
      rates, has consequently increased. Lastly, the results yielded by linked elbow
      prosthesis in post-traumatic conditions are good, although not quite as good as
      those obtained in rheumatoid arthritis. Early mechanical failure may occur in
      younger and more active patients after elbow arthroplasty. However, the careful
      selection of patients who are prepared to accept functional limitations imposed
      by elbow implants will enable indications for elbow arthroplasty to be extended
      to young subjects, particularly when no other therapeutic options are available. 

PMID- 24112702
TI  - Megaprosthesis in large bone defects: opportunity or chimaera?
AB  - INTRODUCTION: The development of new megaprosthesis for the treatment of large
      bone defects provides important options to orthopaedic oncologic surgeons for the
      replacement of skeletal segments, such as the long bones of the upper and lower
      limbs and the relative joints. We implanted megaprosthesis using either a one
      step or two-step technique depending on the patient's condition. The aim of this
      study was to evaluate retrospectively both clinical and radiological outcomes in
      patients who underwent lower limb megaprosthesis implant. MATERIALS AND METHODS:
      A total of 32 patients were treated with mono- and bi-articular megaprosthesis
      subdivided as follows: proximal femur, distal femur, proximal tibia and total
      femur. The mean follow-up of patients was about 18 months (range 3 months to 5
      years). Clinical and serial radiographic evaluations were conducted using
      standard methods (X-ray at 45 days, 3, 6, 12, 18 and 24 months) and blood
      parameters of inflammation were monitored for at least 2 months. RESULTS:
      Although the mean length of follow-up was only 18 months, the first patients to
      enter the study were monitored for 5 years and showed encouraging clinical
      results, with good articulation of the segments, no somato-sensory or motor
      deficit and acceptable functional recovery. During surgery and, more importantly,
      in pre-operative planning, much attention should be given to the evaluation of
      the extensor apparatus, preserving it and, when necessary, reinforcing it with
      tendon substitutes. DISCUSSION: Megaprosthesis in extreme cases of severe bone
      loss and prosthetic failure is a potential solution for the orthopaedic surgeon.
      In oncological surgery, the opportunity to restore functionality to the patient
      (although not ad integrum) is important for both the patient and the surgeon. The
      high mortality associated with cancer precludes long-term patient follow-up;
      therefore, there is a lack of certainty about the survival of this type of
      prosthesis and any medium- to long-term complications that may occur.
      Nevertheless, patients should be considered as an oncologic patient, not because
      of the disease, but because of the limited therapeutic options available.
      CONCLUSIONS: Megaprosthesis provides a valuable opportunity to restore
      functionality to patients with highly disabling diseases.

PMID- 24112703
TI  - Assessing the extirpative quality of a radical prostatectomy technique:
      categorisation and mapping of technical errors.
AB  - OBJECTIVE: To examine the extirpative quality of an open radical prostatectomy
      (RP) technique by first categorising and mapping all intraprostatic incisions
      into benign tissue and then determining a cumulative technical error rate given
      by all intraprostatic incisions into benign and malignant tissue. PATIENTS AND
      METHODS: We performed a retrospective review of prospectively collected data
      relating to 1065 men with clinically localised prostate cancer who underwent open
      retropubic RP (70.6% nerve-sparing surgery [NSS]) by a single surgeon (January
      2005 to December 2011). We recorded all intraprostatic incisions: (i) iatrogenic
      positive surgical margins (PSMs), (ii) deep or superficial benign capsular
      incisions (BCIs), (iii) incisions into benign prostate glands at the prostate
      apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined
      incision location, length and nature (solitary/multiple). We evaluated: (i)
      associations between benign incisions, NSS and PSMs, (ii) significant predictors
      for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence
      (BCR)-free survival (Kaplan-Meier method). RESULTS: Intraprostatic incision rates
      were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in
      rate over time and with NSS technique. Benign incisions were located as follows:
      46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for
      BCIs; 58.6% bladder neck and 41.4% apical for BGTIs. The median (range) incision
      length, for solitary and multiple incisions respectively, was 4 (1-13) and 9 (2
      25) mm for BCIs and 1 (1-5) and 2 (2-6) mm for BGTIs. BCI rate, but not BGTI
      rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and
      increased PSM risk 3.6-fold. A PSM increased BCR risk two-fold (odds ratio 2.078,
      95% confidence interval 1.383-3.122). BCR-free survival decreased significantly
      even for short PSMs (<1 mm; P < 0.001). CONCLUSIONS: Although the pT2 PSM rate
      was low (2.3%), the cumulative technical error rate (patients with at least one
      pT2 PSM, BCI or BGTI) was five-fold higher (12.5%). Categorising and mapping
      intraprostatic incisions is a tool surgeons can use in self-audits to identify
      areas of potential improvement, reduce errors, and improve surgical skills.

PMID- 24112704
TI  - Nitrogen deposition alters plant-fungal relationships: linking belowground
      dynamics to aboveground vegetation change.
AB  - Nitrogen (N) deposition rates are increasing globally due to anthropogenic
      activities. Plant community responses to N are often attributed to altered
      competitive interactions between plants, but may also be a result of microbial
      responses to N, particularly root-associated fungi (RAF), which are known to
      affect plant fitness. In response to N, Deschampsia cespitosa, a codominant plant
      in the alpine tundra at Niwot Ridge (CO), increases in abundance, while Geum
      rossii, its principal competitor, declines. Importantly, G. rossii declines with
      N even in the absence of its competitor. We examined whether contrasting host
      responses to N are associated with altered plant-fungal symbioses, and whether
      the effects of N are distinct from effects of altered plant competition on RAF,
      using 454 pyrosequencing. Host RAF communities were distinct (only 9.4% of OTUs
      overlapped). N increased RAF diversity in G. rossii, but decreased it in D.
      cespitosa. D. cespitosa RAF communities were more responsive to N than G. rossii
      RAF communities, perhaps indicating a flexible microbial community aids host
      adaptation to nutrient enrichment. Effects of removing D. cespitosa were distinct
      from effects of N on G. rossii RAF, and D. cespitosa presence reversed RAF
      diversity response to N. The most dominant G. rossii RAF order, Helotiales, was
      the most affected by N, declining from 83% to 60% of sequences, perhaps
      indicating a loss of mutualists under N enrichment. These results highlight the
      potential importance of belowground microbial dynamics in plant responses to N
      deposition. 

PMID- 24112705
TI  - Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase
      domain.
AB  - Resistance to the BRAF inhibitor vemurafenib poses a significant problem for the
      treatment of BRAFV600E-positive melanomas. It is therefore critical to
      prospectively identify all vemurafenib resistance mechanisms prior to their
      emergence in the clinic. The vemurafenib resistance mechanisms described to date
      do not result from secondary mutations within BRAFV600E. To search for possible
      mutations within BRAFV600E that can confer drug resistance, we developed a
      systematic experimental approach involving targeted saturation mutagenesis,
      selection of drug-resistant variants, and deep sequencing. We identified a single
      nucleotide substitution (T1514A, encoding L505H) that greatly increased drug
      resistance in cultured cells and mouse xenografts. The kinase activity of
      BRAFV600E/L505H was higher than that of BRAFV600E, resulting in cross-resistance
      to a MEK inhibitor. However, BRAFV600E/L505H was less resistant to several other
      BRAF inhibitors whose binding sites were further from L505 than that of PLX4720.
      Our results identify a novel vemurafenib-resistant mutant and provide insights
      into the treatment for melanomas bearing this mutation. 

PMID- 24112706
TI  - Structural and mechanistic insights into collagen degradation by a bacterial
      collagenolytic serine protease in the subtilisin family.
AB  - A number of proteases in the subtilisin family derived from environmental or
      pathogenic microorganisms have been reported to be collagenolytic serine
      proteases. However, their collagen degradation mechanisms remain unclear. Here,
      the degradation mechanism of type I collagen fibres by the S8 collagenolytic
      protease MCP-01, from Pseudoalteromonas sp. SM9913, was studied. Atomic force
      microscopy observation and biochemical analysis confirmed that MCP-01
      progressively released single fibrils from collagen fibres and released collagen
      monomers from fibrils mainly by hydrolysing proteoglycans and telopeptides in the
      collagen fibres. Structural and mutational analyses indicated that an enlarged
      substrate-binding pocket, mainly composed of loops 7, 9 and 11, is necessary for
      collagen recognition and that the acidic and aromatic residues on these loops
      form a negatively charged, hydrophobic environment for collagen binding. MCP-01
      displayed a non-strict preference for peptide bonds with Pro or basic residues at
      the P1 site and/or Gly at the P1' site in collagen. His211 is a key residue for
      the P1-basic-residue preference of MCP-01. Our study gives structural and
      mechanistic insights into collagen degradation of the S8 collagenolytic protease,
      which is helpful in developing therapeutics for diseases with S8 collagenolytic
      proteases as pathogenic factors and in studying environmental organic nitrogen
      degradation mechanisms. 

PMID- 24112707
TI  - Detection of a latent soluble form of membrane type 1 matrix metalloprotease
      bound with tissue inhibitor of matrix metalloproteinases-2 in periprosthetic
      tissues and fluids from loose arthroplasty endoprostheses.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is implicated in pericellular
      proteolysis, and, together with tissue inhibitor of matrix metalloproteinases-2
      (TIMP-2), in the activation of pro-matrix metalloproteinase-2 on the cell
      surface. It is expressed on the cell surface either activated or as a proenzyme.
      A soluble form of MT1-MMP (sMT1-MMP) has been previously identified in
      periprosthetic tissues and fluid of patients with loose arthroplasty
      endoprostheses. The aim of this study was to examine periprosthetic tissues and
      fluids from patients with loose arthroplasty endoprostheses, as well as tissues
      and fluids from patients with other disorders, for the presence of sMT1-MMP, and
      to investigate its activation state and possible role. With antibody against MT1
      MMP, a protein with molecular mass of ~ 57 kDa was detected by western blotting
      in all samples tested, representing a soluble form of MT1-MMP, which cannot be
      ascribed to alternative splicing, as northern blotting showed only one
      transcript. With various biochemical methods, it was shown that this species
      occurs in a latent form bearing the N-terminal prodomain, and, additionally, it
      is bound to TIMP-2, which appeared to be bound via its C-terminal domain to a
      site different from the active site. Cell ELISA and immunohistochemical analysis
      revealed that, besides fibroblasts, all other cells, such as inflammatory,
      epithelial, endothelial, giant and cancer cells, express MT1-MMP on their plasma
      membrane as a proenzyme. Taking into account the proteolytic abilities of MT1
      MMP, the latent sMT1-MMP-TIMP-2 complex could be considered as a new interstitial
      collagenase. However, the exact role, the production mechanism and the cell
      origin of this complex remain to be elucidated. 

PMID- 24112708
TI  - Genome analysis of Chitinivibrio alkaliphilus gen. nov., sp. nov., a novel
      extremely haloalkaliphilic anaerobic chitinolytic bacterium from the candidate
      phylum Termite Group 3.
AB  - Anaerobic enrichments from hypersaline soda lakes with chitin as substrate
      yielded five closely related anaerobic haloalkaliphilic isolates growing on
      insoluble chitin by fermentation at pH 10 and salinities up to 3.5 M. The
      chitinolytic activity was exclusively cell associated. To better understand the
      biology and evolutionary history of this novel bacterial lineage, the genome of
      the type strain ACht1 was sequenced. Analysis of the 2.6 Mb draft genome revealed
      enzymes of chitin-degradation pathways, including secreted cell-bound chitinases.
      The reconstructed central metabolism revealed pathways enabling the fermentation
      of polysaccharides, while it lacks the genes needed for aerobic or anaerobic
      respiration. The Rnf-type complex, oxaloacetate decarboxylase and sodium
      transporting V-type adenosine triphosphatase were identified among putative
      membrane-bound ion pumps. According to 16S ribosomal RNA analysis, the isolates
      belong to the candidate phylum Termite Group 3, representing its first culturable
      members. Phylogenetic analysis using ribosomal proteins and taxonomic
      distribution analysis of the whole proteome supported a class-level
      classification of ACht1 most probably affiliated to the phylum Fibribacteres.
      Based on phylogenetic, phenotypic and genomic analyses, the novel bacteria are
      proposed to be classified as Chitinivibrio alkaliphilus gen. nov., sp. nov.,
      within a novel class Chitinivibrione. 

PMID- 24112709
TI  - Effectiveness of cervical spinal cord stimulation for the management of chronic
      pain.
AB  - INTRODUCTION: Scientific evidence supports spinal cord stimulation (SCS) as a
      cost-effective treatment option that, for many disease states, should be employed
      earlier in the treatment continuum. Reimbursement for SCS in the cervical spine
      has recently been challenged based on supposed lack of clinical literature. To
      refute this assumption, we analyzed data from an international registry to
      support the use of cervical SCS. MATERIALS AND METHODS: The following outcomes
      were collected as part of an institutional review board-approved, prospective,
      multicenter, international registry: pain relief, Pain Disability Index (PDI)
      score, quality of life (QoL), and satisfaction at 3, 6, and 12 months post
      implantation. Descriptive statistics are provided for all measures. Changes from
      baseline in PDI scores were analyzed using Tukey's pairwise comparisons. RESULTS:
      Thirty-eight patients underwent implantation of SCS leads in the cervical spine
      at 16 study sites in the United States and 3 international study sites. Direct
      patient report of percentage of pain relief was 54.2%, 60.2%, and 66.8% at 3, 6,
      and 12 months post-implantation, respectively. Pain relief was categorized as
      excellent/good by 61.6% of patients at 3 months, with similar results observed at
      6 and 12 months. PDI scores were significantly reduced at all time points. At 3
      months post-implantation, 92.4% of patients indicated they were very
      satisfied/satisfied with the SCS device. No patients indicated that they were
      dissatisfied. Overall QoL was reported as improved/greatly improved by 73.1% of
      patients at 3 months. Similar results for QoL and satisfaction were reported at 6
      and 12 months. CONCLUSION: The results suggest that the use of SCS in the
      cervical spine is a medically effective method of pain management that satisfies
      and improves the QoL of most patients. The use of SCS can reduce the high cost of
      direct medical treatment of pain, as well as increasing the productivity of
      patients, and therefore should be reimbursed in appropriately selected patients.

PMID- 24112710
TI  - Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric
      modeling perspective.
AB  - BACKGROUND: The energetics of cerebral activity critically relies on the
      functional and metabolic interactions between neurons and astrocytes. Important
      open questions include the relation between neuronal versus astrocytic energy
      demand, glucose uptake and intercellular lactate transfer, as well as their
      dependence on the level of activity. RESULTS: We have developed a large-scale,
      constraint-based network model of the metabolic partnership between astrocytes
      and glutamatergic neurons that allows for a quantitative appraisal of the extent
      to which stoichiometry alone drives the energetics of the system. We find that
      the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the
      uncoupling between glucose and oxygen utilization at increasing Vcyc levels.
      Thus, we are able to characterize different activation states in terms of the
      tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and
      metabolized according to cellular energy requirements, and that partitioning of
      the sugar between different cell types is not significantly affected by Vcyc.
      Furthermore, both the direction and magnitude of the lactate shuttle between
      neurons and astrocytes turn out to depend on the relative cell glucose uptake
      while being roughly independent of Vcyc. CONCLUSIONS: These findings suggest
      that, in absence of ad hoc activity-related constraints on neuronal and
      astrocytic metabolism, the glutamate-glutamine cycle does not control the
      relative energy demand of neurons and astrocytes, and hence their glucose uptake
      and lactate exchange.

PMID- 24112711
TI  - [Cardiac magnetic resonance with a MRI compatible pacemaker].
AB  - Patients with cardiac implantable electronic devices are usually excluded from
      MRI examinations due to contraindication for MRI. The MRI-conditional pacemaker
      system may allow the benefits of MRI (system 1.5T) to be more accessible to
      pacemaker patients. A 62-year-old man was admitted with acute coronary syndrome
      and atrial fibrillation. A conventional angiography showed normal coronaries. A
      cardiac cardioversion revealed a significant sinus node dysfunction and a
      magnetic resonance imaging (MRI) compatible dual chamber system was implanted. At
      6-week follow-up, a cardiac MRI revealed a typical anterior myocardial infarction
      with diagnostic quality images despite pacemaker. This is one of the first
      reports of cardiovascular MRI in a patient with MRI-conditional pacing system. 

PMID- 24112712
TI  - [Undifferentiated sarcoma: usefulness of multimodality cardiac imaging in
      characterizing a rare intracardiac mass].
AB  - We report the case of a man presenting with a Pierre Marie-Bamberger syndrome.
      This paraneoplastic syndrome revealed an undifferentiated intracardiac sarcoma.
      This case emphasizes the need for multimodality imaging to characterize
      intracardiac tumor. 

PMID- 24112714
TI  - Accumulation and post-translational modifications of plant tubulins.
AB  - The microtubular cytoskeleton of plant cells provides support for several
      functions (including the anchoring of proteins, assembly of the mitotic spindle,
      cytoplasmic streaming and construction of cell walls). Both alpha- and beta
      tubulins are encoded through multigene families that are differentially expressed
      in different organs and tissues. To increase the variability of expression, both
      protein subunits are subjected to post-translational modifications, which could
      contribute to the assembly of specific microtubule structures. This review aims
      to highlight the role of specific post-translational modifications of tubulin in
      plant cells. We initially describe the expression and accumulation of alpha- and
      beta-tubulin isoforms in different plants and at different stages of plant
      development. Second, we discuss the different types of post-translational
      modifications that, by adding or removing specific functional groups, increase
      the isoform heterogeneity and functional variability of tubulin. Modifications
      are proposed to form a 'code' that can be read by proteins interacting with
      microtubules. Therefore, the subpopulations of microtubules may bind to different
      associated proteins (motor and non-motor), thus creating the physical support for
      various microtubule functions.

PMID- 24112713
TI  - Characterization of the heart transcriptome of the white shark (Carcharodon
      carcharias).
AB  - BACKGROUND: The white shark (Carcharodon carcharias) is a globally distributed,
      apex predator possessing physical, physiological, and behavioral traits that have
      garnered it significant public attention. In addition to interest in the genetic
      basis of its form and function, as a representative of the oldest extant jawed
      vertebrate lineage, white sharks are also of conservation concern due to their
      small population size and threat from overfishing. Despite this, surprisingly
      little is known about the biology of white sharks, and genomic resources are
      unavailable. To address this deficit, we combined Roche-454 and Illumina
      sequencing technologies to characterize the first transciptome of any tissue for
      this species. RESULTS: From white shark heart cDNA we generated 665,399 Roche 454
      reads (median length 387-bp) that were assembled into 141,626 contigs (mean
      length 503-bp). We also generated 78,566,588 Illumina reads, which we aligned to
      the 454 contigs producing 105,014 454/Illumina consensus sequences. To these, we
      added 3,432 non-singleton 454 contigs. By comparing these sequences to the
      UniProtKB/Swiss-Prot database we were able to annotate 21,019 translated open
      reading frames (ORFs) of >= 20 amino acids. Of these, 19,277 were additionally
      assigned Gene Ontology (GO) functional annotations. While acknowledging the
      limitations of our single tissue transcriptome, Fisher tests showed the white
      shark transcriptome to be significantly enriched for numerous metabolic GO terms
      compared to the zebra fish and human transcriptomes, with white shark showing
      more similarity to human than to zebra fish (i.e. fewer terms were significantly
      different). We also compared the transcriptome to other available elasmobranch
      sequences, for signatures of positive selection and identified several genes of
      putative adaptive significance on the white shark lineage. The white shark
      transcriptome also contained 8,404 microsatellites (dinucleotide, trinucleotide,
      or tetranucleotide motifs >= five perfect repeats). Detailed characterization of
      these microsatellites showed that ORFs with trinucleotide repeats, were
      significantly enriched for transcription regulatory roles and that trinucleotide
      frequency within ORFs was lower than for a wide range of taxonomic groups
      including other vertebrates. CONCLUSION: The white shark heart transcriptome
      represents a valuable resource for future elasmobranch functional and comparative
      genomic studies, as well as for population and other biological studies vital for
      effective conservation of this globally vulnerable species.

PMID- 24112715
TI  - Systematic literature review and meta-analysis of the efficacy and safety of
      prescription opioids, including abuse-deterrent formulations, in non-cancer pain
      management.
AB  - OBJECTIVE: This study was conducted to compare safety and efficacy outcomes
      between opioids formulated with technologies designed to deter or resist
      tampering (i.e., abuse-deterrent formulations [ADFs]) and non-ADFs for commonly
      prescribed opioids for treatment of non-cancer pain in adults. METHODS: PubMed
      and Cochrane Library databases were searched for opioid publications between
      September 1, 2001 and August 31, 2011, and pivotal clinical trials from all
      years; abstracts from key pain conferences (2010-2011) were also reviewed. One
      hundred and ninety-one publications were initially identified, 68 of which met
      eligibility criteria and were systematically reviewed; a subset of 16 involved a
      placebo group (13 non-ADFs vs placebo, 3 ADFs vs placebo) and reported both
      efficacy and safety outcomes, and were included for a meta-analysis. Summary
      estimates of standardized difference in mean change of pain intensity (DMCPI),
      standardized difference in sum of pain intensity difference (DSPID), and odds
      ratios (ORs) of each adverse event (AE) were computed through random-effects
      estimates for ADFs (and non-ADFs) vs placebo. Indirect treatment comparisons were
      conducted to compare ADFs and non-ADFs. RESULTS: Summary estimates for
      standardized DMCPI and for standardized DSPID indicated that ADFs and non-ADFs
      showed significantly greater efficacy than placebo in reducing pain intensity.
      Indirect analyses assessing the efficacy outcomes between ADFs and non-ADFs
      indicated that they were not significantly different (standardized DMCPI [0.39
      {95% confidence interval (CI) 0.00-0.76}]; standardized DSPID [-0.22 {95% CI 
      0.74 to 0.30}]). ADFs and non-ADFs both were associated with higher odds of AEs
      than placebo. Odds ratios from indirect analyses comparing AEs for ADFs vs non
      ADFs were not significant (nausea, 0.87 [0.24-3.12]; vomiting, 1.54 [0.40-5.97];
      dizziness/vertigo, 0.61 [0.21-1.76]; headache, 1.42 [0.57-3.53];
      somnolence/drowsiness, 0.47 [0.09-2.58]; constipation, 0.64 [0.28-1.49]; pruritus
      0.41 [0.05-3.51]). CONCLUSION: ADFs and non-ADFs had comparable efficacy and
      safety profiles, while both were more efficacious than placebo in reducing pain
      intensity.

PMID- 24112716
TI  - Mapping of allosteric druggable sites in activation-associated conformers of the
      M2 muscarinic receptor.
AB  - G-protein-coupled receptors (GPCRs) are key cellular signaling proteins and have
      been targeted by approximately 30-40% of marketed drugs for treating many human
      diseases including cancer and heart failure. Recently, we directly observed
      activation of the M2 muscarinic receptor through long-timescale accelerated
      molecular dynamics (aMD) simulation, which revealed distinct inactive,
      intermediate and active conformers of the receptor. Here, FTMAP is applied to
      search for 'hot spots' in these activation-associated conformers using a library
      of 16 organic probe molecules that represent fragments of potential drugs. Seven
      allosteric (non-orthosteric) binding sites are identified in the M2 receptor
      through the FTMAP analysis. These sites are distributed in the solvent-exposed
      extracellular and intracellular mouth regions, as well as the lipid-exposed
      pockets formed by the transmembrane alpha helices TM3-TM4, TM5-TM6 and TM7
      TM1/TM2. They serve as promising target sites for designing novel allosteric
      modulators as receptor-selective drugs. 

PMID- 24112718
TI  - Detecting somatic point mutations in cancer genome sequencing data: a comparison
      of mutation callers.
AB  - BACKGROUND: Driven by high throughput next generation sequencing technologies and
      the pressing need to decipher cancer genomes, computational approaches for
      detecting somatic single nucleotide variants (sSNVs) have undergone dramatic
      improvements during the past 2 years. The recently developed tools typically
      compare a tumor sample directly with a matched normal sample at each variant
      locus in order to increase the accuracy of sSNV calling. These programs also
      address the detection of sSNVs at low allele frequencies, allowing for the study
      of tumor heterogeneity, cancer subclones, and mutation evolution in cancer
      development. METHODS: We used whole genome sequencing (Illumina Genome Analyzer
      IIx platform) of a melanoma sample and matched blood, whole exome sequencing
      (Illumina HiSeq 2000 platform) of 18 lung tumor-normal pairs and seven lung
      cancer cell lines to evaluate six tools for sSNV detection: EBCall, JointSNVMix,
      MuTect, SomaticSniper, Strelka, and VarScan 2, with a focus on MuTect and VarScan
      2, two widely used publicly available software tools. Default/suggested
      parameters were used to run these tools. The missense sSNVs detected in these
      samples were validated through PCR and direct sequencing of genomic DNA from the
      samples. We also simulated 10 tumor-normal pairs to explore the ability of these
      programs to detect low allelic-frequency sSNVs. RESULTS: Out of the 237 sSNVs
      successfully validated in our cancer samples, VarScan 2 and MuTect detected the
      most of any tools (that is, 204 and 192, respectively). MuTect identified 11 more
      low-coverage validated sSNVs than VarScan 2, but missed 11 more sSNVs with
      alternate alleles in normal samples than VarScan 2. When examining the false
      calls of each tool using 169 invalidated sSNVs, we observed >63% false calls
      detected in the lung cancer cell lines had alternate alleles in normal samples.
      Additionally, from our simulation data, VarScan 2 identified more sSNVs than
      other tools, while MuTect characterized most low allelic-fraction sSNVs.
      CONCLUSIONS: Our study explored the typical false-positive and false-negative
      detections that arise from the use of sSNV-calling tools. Our results suggest
      that despite recent progress, these tools have significant room for improvement,
      especially in the discrimination of low coverage/allelic-frequency sSNVs and
      sSNVs with alternate alleles in normal samples.

PMID- 24112717
TI  - Programming implantable cardioverter-defibrillators in patients with primary
      prevention indication to prolong time to first shock: results from the PROVIDE
      study.
AB  - BACKGROUND: Shock therapy delivery by implantable cardioverter-defibrillators
      (ICD) can be painful and may have adverse consequences. Reducing shock burden for
      patients with ICDs would be beneficial. METHODS: PROVIDE was a prospective,
      randomized study of primary prevention ICD patients. Patients in the experimental
      group received a combination of programmed parameters with higher detection
      rates, longer detection intervals, empiric antitachycardia pacing (ATP), and
      optimized supraventricular tachycardia (SVT) discriminators, while those in the
      control group were programmed with conventional parameters. Shock therapy and
      arrhythmic syncope were compared. RESULTS: Of 1,670 patients enrolled (846 in the
      experimental group, 824 in the control group) and monitored over a follow-up of
      530 +/- 241 days, 202 patients received shock therapy for any cause (82 in the
      experimental group and 120 in the control group). The median time to first shock
      was significantly prolonged (13.1 vs 7.8 months, hazard ratio [HR]: 0.62, 95%
      confidence interval [CI]: 0.47 to 0.82, P = 0.0005) and the 2-year shock rate
      significantly reduced (12.4% vs 19.4%, P < 0.001) in the experimental group
      compared to the control group. There was no increase in arrhythmic syncope (HR:
      1.64, 95% CI: 0.69 to 3.90, P = 0.26), while the overall mortality was reduced
      (HR: 0.7, 95% CI: 0.50 to 0.98, P = 0.036) in the experimental group compared to
      the control group. CONCLUSION: A combination of programmed parameters utilizing
      higher detection rate, longer detection intervals, empiric ATP, and optimized SVT
      discriminators reduced ICD therapies without increasing arrhythmic syncope and
      was associated with reduction in all-cause mortality among ICD patients.

PMID- 24112719
TI  - Heregulin induces resistance to lapatinib-mediated growth inhibition of HER2
      amplified cancer cells.
AB  - Human epidermal growth factor receptor 2 (HER2) amplification occurs in
      approximately 20% of gastric and gastroesophageal junction cancers in the United
      States and European Union. Lapatinib, a dual HER2 and epidermal growth factor
      receptor tyrosine kinase inhibitor, has demonstrated clinical efficacy in HER2
      amplified cancer cells. However, several studies have shown that some cytokines
      can mediate resistance to lapatinib using their receptor tyrosine kinase (RTK)
      pathways. One of these, Heregulin1 (HRG1), can confer resistance to lapatinib
      mediated growth inhibition in HER2-amplified breast cancer cells, but the
      underlying mechanisms remain unknown. Here, we investigated whether and how HRG1
      causes resistance to lapatinib in gastric and gastroesophageal junction cancers
      in vitro. HER2-amplified gastric and gastroesophageal junction cancer cell lines
      were highly sensitive to lapatinib. Exposure to HRG1 together with lapatinib
      rescued cells from lapatinib-induced cell cycle arrest and apoptosis.
      Downregulation of HER3 with siRNA in the presence of HRG1 re-sensitized HER2
      amplified cancer cells to lapatinib. Immunoblotting analysis indicated that HRG1
      re-activated HER3 and AKT in the presence of lapatinib, which persisted for at
      least 72 h. Activation of HER3 and downstream AKT was mediated by residual
      activity of HER2. HRG1-mediated resistance could be reduced by PI3K/mTOR
      inhibitors or by complete inhibition of HER2. Thus, we conclude that HRG1
      mediates resistance to lapatinib through HER3 and AKT activation, and that this
      depends on residual HER2 activity. Lapatinib in combination with anti-PI3K
      therapies or more potent HER2 inhibitors would improve the efficacy and avoid the
      emergence of resistant cells.

PMID- 24112720
TI  - ABCG9, ABCG11 and ABCG14 ABC transporters are required for vascular development
      in Arabidopsis.
AB  - In order to obtain insights into the regulatory pathways controlling phloem
      development, we characterized three genes encoding membrane proteins from the G
      sub-family of ABC transporters (ABCG9, ABCG11 and ABCG14), whose expression in
      the phloem has been confirmed. Mutations in the genes encoding these dimerizing
      'half transporters' are semi-dominant and result in vascular patterning defects
      in cotyledons and the floral stem. Co-immunoprecipitation and bimolecular
      fluorescence complementation experiments demonstrated that these proteins
      dimerize, either by flexible pairing (ABCG11 and ABCG9) or by forming strict
      heterodimers (ABCG14). In addition, metabolome analyses and measurement of sterol
      ester contents in the mutants suggested that ABCG9, ABCG11 and ABCG14 are
      involved in lipid/sterol homeostasis regulation. Our results show that these
      three ABCG genes are required for proper vascular development in Arabidopsis
      thaliana. 

PMID- 24112721
TI  - MMP20 and KLK4 activation and inactivation interactions in vitro.
AB  - OBJECTIVE: Enamelysin (MMP20) and kallikrein 4 (KLK4) are believed to be
      necessary to clear proteins from the enamel matrix of developing teeth. MMP20 is
      expressed by secretory stage ameloblasts, while KLK4 is expressed from the
      transition stage throughout the maturation stage. The aim of this study is to
      investigate the activation of KLK4 by MMP20 and the inactivation of MMP20 by
      KLK4. DESIGN: Native pig MMP20 (pMMP20) and KLK4 (pKLK4) were isolated directly
      from enamel scrapings from developing molars. Recombinant human proKLK4 (rh
      proKLK4) was activated by incubation with pMMP20 or recombinant human MMP20
      (rhMMP20), and the resulting KLK4 activity was detected by zymography. Reaction
      products were isolated by reverse-phase high performance liquid chromatography
      (RP-HPLC), and their N-termini characterized by Edman degradation. The pMMP20 was
      incubated with pKLK4 under mildly acidic or under physiologic conditions, and
      enzyme activity was analyzed by zymography. The catalytic domain of rhMMP20 was
      incubated with pKLK4 or recombinant human KLK4 (rhKLK4) and the digestion
      products were characterized by zymography and Edman degradation. RESULTS: Both
      pMMP20 and rhMMP20 activated rh-proKLK4 by cleaving at the propeptide-enzyme
      junction used in vivo. The pMMP20 was inactivated by pKLK4 under physiologic
      conditions, but not under mildly acidic conditions. Both pKLK4 and rhKLK4 cleaved
      MMP20 principally at two sites in the catalytic domain of MMP20. CONCLUSIONS:
      MMP20 activates proKLK4 and KLK4 inactivates MMP20 in vitro, and these actions
      are likely to occur during enamel formation in vivo.

PMID- 24112722
TI  - Bacteriological findings in radicular cyst and keratocystic odontogenic tumour
      fluids from asymptomatic patients.
AB  - OBJECTIVE: In this study the potential presence of bacteria in radicular cyst
      (RC) and keratocystic odontogenic tumour(KCOT) fluids from clinically
      asymptomatic patients was investigated. MATERIALS AND METHODS: Cyst fluids were
      collected by needle aspiration from 16 patients with asymptomatic osteolytic
      lesions (10 RCs and 6 KCOTs) undergoing surgery. All samples were transferred
      into tubes containing pre-reduced transport medium, delivered to the microbiology
      laboratory and processed within 1h. The cysts, surgically enucleated, were sent
      for standard histopathological examination. Cyst fluid samples were cultured on
      selective and differential media in anaerobic (for about 2 weeks) and aerobic
      (for 24-48 h) conditions to detect viable microorganisms. After incubation, the
      colonies were counted, Gram-stained and identified by biochemical tests. RESULTS:
      Cultures were positive for the presence of bacteria in 15 (9 RCs, 6 KCOTs) out of
      16 cases. RCs and KCOTs generally yielded low bacterial counts (10(2)-10(4)
      CFU/ml) and were predominantly colonized by obligate anaerobes (64%), whereas
      less commonly by facultative anaerobes (36%). No significant differences in the
      detection frequencies of obligate and facultative anaerobes were evidenced
      between RCs and KCOTs. Propionibacterium acnes was the most common obligate
      anaerobe recovered both in RC and KCOT fluids. Among facultative anaerobes,
      Gemella morbillorum was more frequently isolated in KCOTs, whereas Staphylococcus
      spp. in RCs. CONCLUSIONS: Bacteria may be present and persist within fluids of
      clinically asymptomatic jaw cystic lesions. The influence of bacteria and latent
      bacterial infection within cystic jaw lesions should be reconsidered in
      odontogenic cyst progression.

PMID- 24112723
TI  - Morphological plasticity of Streptococcus oralis isolates for biofilm production,
      invasiveness, and architectural patterns.
AB  - OBJECTIVE: Streptococcus oralis is an early coloniser of the oral cavity that
      contributes to dental plaque formation. Many different genotypes can coexist in
      the same individual and cause opportunistic infections such as bacterial
      endocarditis. However, little is known about virulence factors involved in those
      processes. The aim was to analyze the evolving growth of S. oralis colony/biofilm
      to find out potentially pathogenic features. DESIGN: Thirty-three S. oralis
      isolates were analyzed for: (1) biofilm production, by spectrophotometric
      microtiter plate assay; (2) colonial internal architecture, by histological
      methods and light and electron microscopy; (3) agar invasion, by a new colony
      biofilm assay. RESULTS: S. oralis colonies showed two different growth patterns:
      (1) fast growth rate without invasion or minimally invasive; (2) slow growth
      rate, but high invasion ability. 12.1% of strains were biofilm non-producers and
      24.2% not invasive, compared to 51.5% biofilm high-producers and 39.4% very
      invasive. Both phenotypic characteristics tended to be mutually exclusive.
      However, a limited number of strains (15%) co-expressed these features at the
      highest level. CONCLUSIONS: Morphological plasticity of S. oralis highlighted in
      this study may have important ecological and clinical implications. Coexistence
      of strains with different growth patterns could produce a synergic effect in the
      formation and development of subgingival dental plaque. Moreover, invasiveness
      might regulate dissemination and colonisation mechanisms. Simultaneous co
      expression of high-invasive and high-biofilm phenotypes gives a fitness advantage
      during colonisation and may confer higher pathogenic potential.

PMID- 24112724
TI  - Differential effect of autoinducer 2 of Fusobacterium nucleatum on oral
      streptococci.
AB  - Autoinducer 2 (AI-2) is a quorum sensing molecule and plays an important role in
      dental biofilm formation, mediating interspecies communication and virulence
      expression of oral bacteria. Fusobacterium nucleatum connects early colonizing
      commensals and late colonizing periodontopathogens. F. nucleatum AI-2 and quorum
      sensing inhibitors (QSIs) can manipulate dental biofilm formation. In this study,
      we evaluated the effect of F. nucleatum AI-2 and QSIs on biofilm formation of
      Streptococcus gordonii and Streptococcus oralis, which are initial colonizers in
      dental biofilm. F. nucleatum AI-2 significantly enhanced biofilm growth of S.
      gordonii and attachment of F. nucleatum to preformed S. gordonii biofilms. By
      contrast, F. nucleatum AI-2 reduced biofilm growth of S. oralis and attachment of
      F. nucleatum to preformed S. oralis biofilms. The QSIs, (5Z)-4-bromo-5
      (bromomethylene)-2(5H)-furanone and d-ribose, reversed the stimulatory and
      inhibitory effects of AI-2 on S. gordonii and S. oralis, respectively. In
      addition, co-culture using a two-compartment system showed that secreted
      molecules of F. nucleatum had the same effect on biofilm growth of the
      streptococci as AI-2. Our results demonstrate that early colonizing bacteria can
      influence the accretion of F. nucleatum, a secondary colonizer, which ultimately
      influences the binding of periodontopathogens. 

PMID- 24112725
TI  - Glucose-free conditions induce the expression of AMPK in dental pulp cells.
AB  - OBJECTIVES: This study is aimed to test whether glucose-free conditions induce
      the activation of adenosine monophosphate-activated protein kinase (AMPK) and, to
      investigate association with AMPK expression and cell viability in human dental
      pulp cells. DESIGN: Human dental pulp cells were initially maintained in culture
      medium containing glucose and the medium was subsequently changed to glucose-free
      medium. To evaluate the expression of AMPK, quantitative real-time RT-PCR,
      Western blot analysis and immunofluorescence were carried out. Cell viability was
      evaluated by MTT assay. RESULTS: The expression of AMPK mRNA in glucose free
      conditions was 2.0-2.5 fold higher than the control at 1, 2 and 3 h (P<0.01). The
      expression of phosphorylated-AMPK was characterized by Western blot analysis and
      by immunofluorescence. Compound C-pre-treated group showed a decline of both AMPK
      expression and cell viability, while AICAR-pre-treated group showed an increase
      of AMPK and maintain of cell viability at regular level. CONCLUSIONS: AMPK plays
      an important role on fluctuating in accordance with glucose availability and
      protects cell viability from glucose free condition in human dental pulp cells.

PMID- 24112726
TI  - Root and canal morphology of mandibular first premolars with radicular grooves.
AB  - OBJECTIVE: To investigate the relation between the radicular groove (RG) and the
      internal root canal morphology in mandibular first premolars by using micro
      computed tomography. METHODS: A total of 249 extracted mandibular first premolars
      were collected from a native Chinese population. After scoring the RGs according
      to the Arizona State University dental anthropology scoring system (ASUDAS), 148
      teeth were selected and scanned by using micro-computed tomography. The root
      canal systems were examined two- and three-dimensionally under the software
      Mimics 10.01. The depth and angle of the RGs at different levels were measured.
      RESULTS: The presence of Tomes' root trait (ASU=3-5) was identified in 47/249 of
      the sample teeth (18.9%). The mean depths of the shallow (ASU=1), moderately deep
      (ASU=2) and deep grooves (ASU=3) were 0.18, 0.36 and 1.24 mm, and the mean angles
      were 28.8 degrees , 47.5 degrees  and 101.7 degrees , respectively. The
      incidences of complicated root canal systems were 15.5% (ASU=0), 18.7% (ASU=1),
      37.0% (ASU=2) and 90.0% (ASU=3). In nine scanned specimens, accessory canals were
      found communicating between the main canal and the RG. Invagination canals were
      observed in four specimens, and C-shaped canals were found in 29 specimens
      (19.6%). CONCLUSIONS: The complexity of root canal systems in mandibular first
      premolars is determined by the severity of RGs, which can be scored by the
      ASUDAS. Detecting the incidence of various root canal forms corresponding to each
      ASUDAS score is useful for calculating the standardized rates from published data
      of dental anthropology. Understanding the anatomic features of the RG and the
      internal root canal system is essential for successful dental treatment.

PMID- 24112727
TI  - Effectiveness of cysteine proteases on protein/pigment film removal.
AB  - OBJECTIVE: Theaflavin (TF) from the black tea can react to human salivary proline
      rich proteins (PRPs) to form stains on exposed dental surfaces. Here, we employed
      a model of protein/pigment film using TF and dephosphorylated bovine beta-casein
      (Dbeta-CN), which has an extended conformation, similar to that of salivary PRPs,
      on a sensor surface to assess the efficacy of cysteine proteases (CPs) including
      papain, stem bromelain, and ficin, on removing TF bound to Dbeta-CN and the
      control TF readsorption on the residual substrate surfaces was also measured.
      METHODS: The protein/pigment complex film was built by using a quartz crystal
      microbalance with dissipation (QCM-D). The efficacies of CPs were assessed by
      Boltzman equation model. The surface details were detected by grazing angle
      infrared spectroscopy spectra, atomic force microscopy images, and contact
      angles. RESULTS: The efficacy order of CPs on hydrolyzing protein/pigment complex
      film is ficin>papain>bromelain. The results from grazing angle infrared
      spectroscopy spectra, atomic force microscopy images, and contact angles
      demonstrated that TF bound on the Dbeta-CN was effectively removed by the CPs,
      and the amount of TF readsorption on both the residual film of the Dbeta-CN/TF
      and the Dbeta-CN was markedly decreased after hydrolysis. CONCLUSION: This study
      indicates the potential application of the CPs for tooth stain removal and
      suggests that these enzymes are worthy of further investigation for use in oral
      healthcare.

PMID- 24112728
TI  - Potential high virulence for infective endocarditis in Streptococcus mutans
      strains with collagen-binding proteins but lacking PA expression.
AB  - OBJECTIVE: Streptococcus mutans, an aetiologic agent of dental caries, is a
      pathogen for infective endocarditis (IE). We investigated strains that express
      collagen-binding proteins (CBPs) with further classification based on expression
      of the 190-kDa protein antigen (PA). METHOD: Zeta-potential values of strains
      TW871 (CBP+/PA+) and MT8148 (CBP-/PA+), and their respective PA-defective mutant
      strains TW871PD (CBP+/PA-) and MT8148PD (CBP-/PA-), were analysed, as were their
      adhesion to and invasion of human umbilical vein endothelial cells (HUVECs). The
      distribution of strains from the oral cavities of 200 healthy individuals was
      analysed for CBP and/or PA expression and the strains were characterised for
      their adhesion and invasion properties. RESULTS: TW871PD and MT8148PD showed
      significantly lower zeta-potential values than TW871 and MT8148, respectively.
      Collagen-binding rates were significantly higher for TW871PD than for TW871 but
      nearly negligible for MT8148 and MT8148PD. The adhesion and invasion rates of
      HUVECs were significantly higher for TW871PD than for TW871 and significantly
      higher for TW871 than for MT8148 and MT8148PD. The prevalence of CBP+ strains was
      ~10% and ~3% in the case of CBP+/PA- strains. Analyses of 200 clinical strains
      showed the CBP+/PA- group to have higher adhesion and invasion rates than other
      groups. CONCLUSIONS: CBP+/PA- S. mutans strains, despite their low distribution
      frequency, may be highly virulent for infective endocarditis.

PMID- 24112729
TI  - Analysis of age-related changes in the functional morphologies of salivary glands
      in mice.
AB  - BACKGROUND AND OBJECTIVES: Salivary glands in the elderly commonly exhibit
      salivary dysfunction resulting dry mouth, poor oral hygiene, and dental caries.
      However, in vivo changes of salivary glands during aging have not been well
      documented in the literature. This study was undertaken to determine age-related
      morphometric and functional changes of salivary glands using an aging mouse
      model. METHODS: Male C57BL/6 mice were divided into three groups, group A (10
      weeks old; n=10), group B (30 weeks old; n=10), and group C (90 weeks old; n=10).
      Body weights, salivary gland weights, salivary flow rates, and salivary lag times
      were measured and compared. Histomorphometric examinations and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were
      performed. In addition, changes in salivary uptake and excretion were observed by
      single-photon emission computed tomography (SPECT). RESULTS: Body and gland
      weights increased with age. Gland weight was significantly higher in group B than
      in groups A and C. Salivary lag time was significantly greater in group C than in
      groups A and B, and salivary flow rate was significantly greater in group B than
      in groups A and C. Histologic evaluations exhibited acinar cell atrophy,
      cytoplasmic vacuolization, lymphocyte infiltration, small mucin component and
      more periductal fibrosis in salivary glands of group C. TUNEL assays revealed
      that apoptotic salivary epithelial cells were significantly more numerous in
      group C than in groups A and B. (99m)Tc-pertechnetate excretion rate was
      significantly lower in group C than in groups A and B in SPECT. CONCLUSION:
      Various morphometric and histopathological changes were observed in the salivary
      glands of aging mouse as well as relevant functional alterations, such as,
      decreased saliva production and excretion. Increased number of apoptotic salivary
      epithelial cells may contribute to the observed functional deterioration.

PMID- 24112730
TI  - Impairment of rat tooth eruption in pups born to mothers exposed to chronic
      stress during pregnancy.
AB  - OBJECTIVE: Tooth eruption is a multifactorial process in which bone tissue plays
      a prevailing role. In this study we evaluated the bone overlying the developing
      tooth germ and the degree of tooth eruption of the first mandibular molar in pups
      born to mothers subjected to constant light during pregnancy. DESIGN: Pregnant
      rats were divided into two groups: mothers chronically exposed to a 12:12
      light/light cycle (LL) from day 10 to 20 of pregnancy and controls (C) maintained
      on a 12:12 h light/dark cycle. Pups from each group were euthanized at the age 3
      or 15 days. Buccolingually oriented sections of mandibles were stained with
      haematoxylin-eosin or for histochemical detection of tartrate resistant acid
      phosphatase (TRAP). The histomorphometric parameters evaluated were bone volume,
      number of osteoclasts, TRAP+ bone surface, number of TRAP+ and TRAP- osteoclasts
      per mm(2) and degree of tooth eruption (mm). RESULTS: It was found an increase in
      bone volume (LL: 58.14+/-4.24 vs. C: 32.31+/-2.16; p<0.01) and a decrease in the
      number of osteoclasts (LL: 3.5+/-0.65 vs. C: 8.03+/-1.31; p<0.01) and TRAP+ cells
      (LL: 0.84+/-0.53 vs. C: 8.59+/-1.26; p<0.01) in 3-day-old pups born to LL-exposed
      mothers. These observations are consistent with the decrease in the degree of
      tooth eruption observed in 15-day-old experimental pups (LL: -0.605+/-0.05 vs. C:
      -0.342+/-0.02; p<0.0001). CONCLUSION: Our results suggest that chronic constant
      light applied as a pre-natal stressor impairs the resorptive capacity of
      osteoclasts involved in the formation of the eruption pathway and consequently
      the degree of tooth eruption.

PMID- 24112731
TI  - Disruption of oral sensory relay to brain increased anxiety- and depression-like
      behaviours in rats.
AB  - OBJECTIVE: Sensory information plays an important role to determine psycho
      emotional behaviours of individuals. Lingual nerve can be damaged by dental
      surgery or trauma, such as physical irritation, radiation, chemotherapy, or viral
      infection. This study was conducted to examine the psycho-emotional effects of
      lingual nerve damage in which oral sensory relay to the brain is disrupted.
      DESIGN: Male Sprague-Dawley rats were tested for anxiety and depression-related
      behaviours after bilateral transections of the lingual and chorda tympani nerves
      (Nx) or sham operation. Tissue contents of serotonin and its metabolite in the
      hippocampus, hypothalamus, and nucleus accumbens were analyzed by high
      performance liquid chromatography. RESULTS: Sucrose preference was reduced in Nx
      rats compared with sham rats, suggesting the development of anhedonia, decreased
      pleasure seeking behaviour, by the lingual nerves transection. Ambulatory
      activity was decreased, anxiety-related behaviours during the activity test
      increased, time spent in the open arms during elevated plus maze test decreased,
      and immobility duration during forced swim test increased in Nx rats compared
      with sham rats. Serotonin level in the hippocampus of Nx rats was decreased
      significantly compared with sham rats. CONCLUSIONS: Results suggest that
      aberration of oral sensory relay to brain may lead to the development of
      depression- and anxiety-related disorders, and decreased serotonergic
      neurotransmission in the hippocampus may play a role in its underlying mechanism.

PMID- 24112732
TI  - Regulation of CCN2 gene expression and possible roles in developing tooth germs.
AB  - CCN proteins are extracellular and cell-associated molecules involved in several
      developmental processes, but their expression patterns and regulation in tooth
      development remain unclear. Here we first determined the expression patterns of
      CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected
      in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN
      family members were expressed broadly. By the bell stage, all members were
      expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2
      transcripts were conspicuous in differentiating osteoblasts in dental follicle.
      Next, we asked what signalling molecules regulate CCN2 expression and what roles
      CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was
      not longer expressed in dental mesenchyme in cultured bud stage germs.
      Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular
      explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent
      effect of BMP-4 on CCN2 induction; a concentration of 100 ng/MUl was able to
      induce strong CCN2 expression while a minimum concentration of 25 ng/MUl was
      needed to elicit appreciable expression. Importantly, Noggin treatment inhibited
      endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in
      developing tooth germs requires BMP signalling. Lastly, we found that rCCN2
      stimulated proliferation in dental mesenchyme in a dose-dependent manner.
      Together, the data indicate that expression of CCN genes is spatio-temporally
      regulated in developing tooth germs. CCN2 expression appears to depend on
      epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong
      proliferation in dental mesenchyme.

PMID- 24112733
TI  - Survival of Enterococcus faecalis during alkaline stress: changes in morphology,
      ultrastructure, physiochemical properties of the cell wall and specific gene
      transcripts.
AB  - OBJECTIVE: The aim of this investigation was to study the biochemical mechanisms
      employed by the endodontic pathogen Enterococcus faecalis to survive alkaline
      environment during biofilm formation. DESIGN: E. faecalis ATCC33186 was
      inoculated in media at pH 7, 9, 10 and 11 for biofilm formation. The morphology
      and ultrastructure of biofilm cells were observed by scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM). The physiochemical properties
      of the cell wall were investigated by measuring the hydrophobicity and Na(+)K(+)
      ATPase and H(+)K(+)-ATPase activity. The expression of stress and virulence genes
      was quantified by real-time quantitative polymerase chain reaction. RESULTS: E.
      faecalis grown in alkaline medium developed an irregular shape and asymmetrical
      septation. The activity of Na(+)K(+)-ATPase increased dramatically with rising
      pH, whereas the activity of H(+)K(+)-ATPase exhibited no increase, except at pH
      10. A marked increase in cell surface hydrophobicity was also observed with
      increased pH and time. In addition, transcription of most of the genes tested
      increased 2- to 15-fold at pH 9 or 10 compared with pH 7 and increased more than
      50-fold at pH 11, which is generally recognised as nearly lethal stress.
      CONCLUSIONS: E. faecalis survival and biofilm formation under alkaline stress was
      unrelated to H(+)K(+)-ATPase but was correlated with an increase in Na(+)K(+)
      ATPase activity and cell-surface hydrophobicity in addition to the up-regulation
      of genes involved in stress response and biofilm formation. These characteristics
      may explain why E. faecalis resists alkaline root canal medications.

PMID- 24112734
TI  - Comparative proteomic analysis of oral squamous cell carcinoma and adjacent non
      tumour tissue from Thailand.
AB  - OBJECTIVE: The study was aimed at analysing and identifying the proteins that are
      differentially expressed in oral squamous cell carcinoma (OSCC) compared to
      adjacent non-tumour tissue. MATERIALS AND METHODS: Two-dimensional (2D) sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis accompanied by mass
      spectrometry (matrix-assisted laser desorption/ionisation-time-of-flight mass
      spectrometry and liquid chromatography-tandem mass spectrometry) was used to
      analyse and identify the differentially expressed proteins in 10 pairs of tumours
      and adjacent non-tumour tissues from five cases of early-stage and five cases of
      late-stage OSCC. The statistical differences of the protein spots were analysed
      by the Wilcoxon signed-rank test. A validation study using immunohistochemistry
      and quantitative real-time reverse transcription-polymerase chain reaction (qRT
      PCR) was performed. RESULTS: A total of 68 proteins (63 up-regulated, five down
      regulated) were differentially expressed in early-stage disease, and 39 proteins
      (37 up-regulated, two down-regulated) were significantly altered in late-stage
      disease. Among these, 14 proteins were altered in both groups. A total of 44
      proteins were identified, including heat shock proteins (HSPs: Hsp90, HSPA5 and
      HSPA8), keratins (K1, K6A and K17), tubulin, cofilin 1, 14-3-3sigma and metabolic
      enzymes. These proteins are involved in various cellular processes essential for
      cell growth, survival and cell migration. The validation study on alpha-tubulin
      and 14-3-3sigma using immunohistochemistry and KIAA1199 expression using real
      time RT-PCR confirmed the results in proteomics analysis. CONCLUSIONS: The study
      identified many proteins, both known and unknown, for cancer cell processes. At
      least two proteins, KIAA1199 and Horf6, are novel for oral cancer.

PMID- 24112735
TI  - Cetylpyridinium chloride suppresses gene expression associated with halitosis.
AB  - OBJECTIVE: Halitosis is a common complaint affecting the majority of the
      population. Mouthrinses containing cetylpyridinium chloride (CPC) have been used
      as oral hygiene aids to suppress oral malodor. Although the clinical efficacy of
      these mouthrinses has been well-documented, the mechanism whereby CPC reduces
      malodor is less-well-understood. We hypothesized that CPC suppresses expression
      of the genes (mgl and cdl) and enzymes responsible for methyl mercaptan (CH3SH)
      and hydrogen sulfide (H2S) production by oral anaerobes associated with
      halitosis. In this study, the mgl and cdl expression of Porphyromonas gingivalis
      and Fusobacterium nucleatum in the presence of CPC was investigated. MATERIALS
      AND METHODS: We used a microdilution method to determine the growth and
      production of volatile sulfur compounds (VSCs) by P. gingivalis W83 and F.
      nucleatum ATCC 10953 in respective media containing CPC (0.5 MUg/mL to 1.5
      MUg/mL). For metabolic activity, we used an XTT {2,3-bis(2-methyloxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide} reduction assay. We used real-time
      RT-PCR and Western blotting to evaluate the effect of CPC at sub-MIC levels on
      mgl and cdl expression at the transcriptional and enzymatic levels. RESULTS: CPC
      inhibited the growth of P. gingivalis and F. nucleatum at MICs of 3 MUg/mL and 2
      MUg/mL, and at MBCs of 6 MUg/mL and 3 MUg/mL, respectively. Compared with
      untreated controls, CPC at 1.5 MUg/mL suppressed CH3SH production of P.
      gingivalis by 69.84%+/-2.88% and H2S production of F. nucleatum by 82.55%+/-8.36%
      (p<0.05) without affecting metabolic activity. Inhibition of mgl mRNA (81.58%+/
      20.33%) and protein (39.15%+/-6.65%) expression in P. gingivalis and inhibition
      of cdl mRNA (61.76%+/-13.75%) and protein (64.34%+/-1.62%) expression in F.
      nucleatum were also noted (p<0.05). CONCLUSION: CPC represents an effective agent
      for halitosis reduction by inhibiting the growth and suppressing the expression
      of specific genes related to VSC production in anaerobic periodontal pathogens.

PMID- 24112736
TI  - Effects of enamel and dentine thickness on laser Doppler blood-flow signals
      recorded from the underlying pulp cavity in human teeth in vitro.
AB  - OBJECTIVE: To determine the effect of enamel and dentine thickness on laser
      Doppler blood-flow (LDF) signals recorded from dental pulp. DESIGN: Observations
      were made on 18 human premolars that had been extracted from young patients
      during orthodontic treatment. The apical 2/3 of the root was cut off and the
      remaining pulp removed. Blood flow signals were recorded from the buccal surface
      of the crown with a laser Doppler flow metre while dilute blood was pumped at 10
      ml/min. through a cannula inserted into the pulp cavity. Recordings were made
      from the enamel surface and at 0.5 mm steps through the enamel and dentine.
      RESULTS: The blood flow signal increased significantly as the cavity depth
      increased and at 2.0 mm, the median flux signal was more than ten times greater
      than that obtained on the enamel surface. The backscattered light intensity did
      not change with cavity depth. CONCLUSION: When recording pulpal blood flow from a
      human tooth with a laser Doppler flow metre, a substantially better signal-to
      noise ratio should be obtained by placing the probe on dentine in the floor of a
      cavity than on the enamel surface.

PMID- 24112737
TI  - The role of phosphoinositide 3-kinase in adhesion of oral epithelial cells to
      titanium.
AB  - BACKGROUND: Oral epithelial cells (OECs) adhesion to titanium may improve the
      success rate of implant restoration. PURPOSE: We investigated the mechanism by
      which OECs adhere to titanium dental implants. MATERIALS AND METHODS: (1) After
      culturing rat OECs on titanium plates (Ti) or culture dishes in the presence or
      absence of a phosphoinositide 3-kinase (PI3K) activator or inhibitors and/or
      growth factors, and OEC morphology under these conditions were analyzed. (2)
      Right maxillary first molars were extracted and replaced with experimental
      implants. The rats were treated with or without growth factors. RESULTS: (1) Cell
      adherence was lower of OECs on Ti than in those on culture dishes, as were the
      levels of integrin beta4 and the continuity of F-actin structures. After PI3K
      inhibition, markedly reducing adherence to both substrates. In contrast, PI3K
      activation with activator or insulin-like growth factor restored the OEC
      adherence and the expression of adhesion molecules on Ti to the levels seen in
      OECs cultured on dishes. Cell migration was inhibited by PI3K activation. (2)
      High expression of integrin beta4 was observed in the peri-implant epithelia of
      PI3K-activated rats. CONCLUSION: These findings suggest that PI3K plays an
      important role in the adhesion of OECs to Ti.

PMID- 24112738
TI  - Dental pulp stem cells from traumatically exposed pulps exhibited an enhanced
      osteogenic potential and weakened odontogenic capacity.
AB  - OBJECTIVES: Traumatic pulp exposure can bring about some permanent damages to
      tooth tissues including dental pulps. This study was designed to evaluate the
      effects of traumatic pulp exposure on the osteo/odontogenic capacity of dental
      pulp stem cells (DPSCs). METHODS: Rat incisors were artificially fractured and
      dental pulps were exposed to the oral environment for 48 h. Then, multi-colony
      derived DPSCs from the injured pulps (iDPSCs) were isolated. Their
      osteo/odontogenic differentiation and the involvement of NF-kappaB pathway were
      subsequently investigated. RESULTS: iDPSCs presented a lower proliferative
      capacity than normal DPSCs (nDPSCs), as indicated by MTT and FCM assay. ALP
      levels in iDPSCs were significantly higher (P<0.01) than those in nDPSCs.
      Alizarin red staining revealed that iDPSCs exhibited an increased capacity of
      calcium deposition. Moreover, iDPSCs expressed stronger osteogenic markers
      (Runx2/RUNX2 and Ocn/OCN) and less odontogenic gene/protein (Dspp/DSP) than
      nDPSCs in vitro. In vivo transplantation showed that nDPSCs implants generated
      the typical dentine-pulp complex while all iDPSCs pellets formed the osteodentin
      like tissues which were immunopositive for OCN. Mechanistically, iDPSCs expressed
      the higher levels of cytoplasmic phosphorylated IkappaBalpha/P65 and nuclear P65
      than nDPSCs, indicating an active cellular NF-kappaB pathway in iDPSCs. After the
      inhibition of NF-kappaB pathway, the osteogenic potential in iDPSCs was
      significantly down-regulated while odontogenic differentiation was up-regulated,
      as indicated by the decreased Alp/Runx2/Ocn and uprised Dspp expression.
      CONCLUSIONS: Pulp exposure for 48 h decreased the odontogenic capacity and
      enhanced the osteogenic potential of DPSCs via the NF-kappaB signalling pathway.

PMID- 24112739
TI  - Response of immortalized murine cementoblast cells to hypoxia in vitro.
AB  - OBJECTIVES: The aim of the study was to investigate the impact of hypoxia on
      proliferation, apoptosis and mineralization of cementoblast-like cells (OCCM-30)
      in vitro. METHODS: The effects of different periods of hypoxia (2% O2) on
      proliferation, apoptosis, cementoblastic potential and root cementum resorption
      capability of OCCM-30 were evaluated, by using MTT, flow cytometry, alkaline
      phosphatase (ALP) activity assay, reverse transcription-polymerase chain reaction
      measurement, enzyme-linked immunosorbent assay and mineralization nodule
      formation assay. RESULTS: OCCM-30 viability was significantly inhibited by
      hypoxia while the apoptosis ratio was enhanced in a time-dependent manner;
      hypoxia inducible factor-1alpha and vascular endothelial growth factor mRNA were
      induced by hypoxia in different manners; temporary hypoxia (<24 h) stimulated
      cementoblastic function of OCCM-30, while long-term hypoxia inhibited it,
      manifested by decreased mRNA level or release of ALP, osteocalcin, bone
      sialoprotein, osteopontin and osteoprotegerin. In addition, hypoxia affected
      mineralized nodule formation of OCCM-30 in a time-dependent fashion; moreover,
      root cementum resorption function was also induced by hypoxia, manifested by
      increased receptor activator of nuclear factor kappa B ligand mRNA and protein
      expression. CONCLUSION: Temporary exposure of OCCM-30 to hypoxia inhibited
      proliferation, promoted apoptosis and mineralization, while longer duration of
      hypoxia could inhibit the cementoblast function. The findings may provide
      theoretical basis for developing novel therapeutics to prevent root resorption
      during orthodontic treatment.

PMID- 24112740
TI  - Mapping the spatial and temporal progression of human dental enamel
      biomineralization using synchrotron X-ray diffraction.
AB  - OBJECTIVE: The complex biological, physicochemical process of human dental enamel
      formation begins in utero and for most teeth takes several years to complete.
      Lost enamel tissue cannot regenerate, therefore a better understanding of the
      spatial and temporal progression of mineralization of this tissue is needed in
      order to design improved in vivo mineral growth processes for regenerative
      dentistry and allow the possibility to grow a synthetic whole or partial tooth.
      METHOD: Human dental enamel samples across a range of developmental stages
      available through archaeological collections have been used to explore the
      spatial and temporal progression of enamel biomineralization. Position sensitive
      synchrotron X-ray diffraction was used to quantify spatial and temporal
      variations in crystallite organization, lattice parameters and crystallite
      thickness at three different stages in enamel maturation. In addition X-ray
      microtomography was used to study mineral content distributions. RESULTS: An
      inverse correlation was found between the spatial variation in mineral content
      and the distribution of crystallite organization and thickness as a function of
      time during enamel maturation. Combined X-ray microtomography and synchrotron X
      ray diffraction results show that as enamel matures the mineral content increases
      and the mineral density distribution becomes more homogeneous. Starting
      concurrently but proceeding at a slower rate, the enamel crystallites become more
      oriented and larger; and the crystallite organization becomes spatially more
      complex and heterogeneous. CONCLUSION: During the mineralization of human dental
      enamel, the rate of mineral formation and mineral organization are not identical.
      Whilst the processes start simultaneously, full mineral content is achieved
      earlier, and crystallite organization is slower and continues for longer. These
      findings provide detailed insights into mineral development in human dental
      enamel which can inform synthetic biomimetic approaches for the benefit of
      clinical dentistry.

PMID- 24112741
TI  - An audit of outcomes after same-day discharge post-PCI in acute coronary syndrome
      and elective patients.
AB  - OBJECTIVES: To investigate the outcomes of a cohort of acute and elective
      percutaneous coronary intervention (PCI) patients who were discharged home 6
      hours postprocedure. BACKGROUND: Contemporary PCI is safe with a low rate of
      acute complications. It is well established as a day procedure in elective cases;
      however, data are lacking in acute cases. METHODS: We describe a prospective
      observational audit of routine clinical practice in the 3 PCI centers in Northern
      Ireland. Patients were selected for same-day discharge after 6 hours of post-PCI
      observation. Both elective and acute coronary syndrome (ACS) cases were included.
      Criteria for same-day discharge were based on the technical result of the
      procedure rather than lesion complexity or clinical presentation. Radial access
      was preferred but not mandatory. Patients were contacted directly to assess for
      30-day major adverse cardiovascular events (MACE). Reported events were
      corroborated with the general practitioner or hospital notes. RESULTS: A total of
      1,059 patients were selected for same-day discharge with 30-day follow-up
      available for all cases. Of these, 766 (72.3%) were elective and 293 (27.7%) were
      ACS patients. Radial access was almost universal (98%). A total of 1,224 lesions
      were stented, of which 432 (40.8%) were high risk (highest risk lesion in each
      case by AHA/ACC classification). MACE rate at 30 days was 0.85% with a sub-acute
      stent thrombosis rate of 0.4%. There were no MACE events from discharge to 24
      hours. CONCLUSIONS: Selected acute and elective patients with a range of lesion
      complexity and risk can be discharged safely home early after PCI.

PMID- 24112742
TI  - Can we improve the definition of high-risk, hormone naive, non-metastatic
      prostate cancer?
AB  - To identify criteria beyond Tumour-Node-Metastasis (TMN)-, prostate-specific
      antigen (PSA)- and Gleason score-based standard classifications to enhance the
      stratification of non-metastatic high-risk prostate cancer. A detailed search of
      the literature was performed using PubMed. The authors reviewed the literature
      and used a modified Delphi approach to identify relevant approaches to enhance
      standard classifications. Specific criteria for high-risk prostate cancer vary
      across guidelines and clinical trials, reflecting the differing perspectives
      concerning the definition of 'risk' between different specialities within the
      urology/radiation oncology community. In addition to the present classifications,
      evidence exists that the measure of cancer volume can provide additional
      prognostic value. More accurate imaging, especially multiparametric magnetic
      resonance imaging can also provide information concerning staging and cancer
      volume, and thus may assist in the identification of patients with high-risk
      prostate cancer. A refined definition of non-metastatic high-risk prostate cancer
      is proposed. Within this high-risk cohort, patients with multiple high-risk
      criteria are especially at risk of prostate cancer-specific mortality. 

PMID- 24112743
TI  - First application of comet assay in blood cells of Mediterranean loggerhead sea
      turtle (Caretta caretta).
AB  - The aim of this study was to validate the comet assay in erythrocytes of Caretta
      caretta, a species never investigated for genotoxicity. We studied 31 loggerhead
      sea turtles from three Italian marine rescue centres. Peripheral blood samples
      were collected from all the animals and the comet assay applied. All comet cells
      were analysed using two methods: visual scoring and computer image analysis. The
      % DNA in tail mean value +/- SD and Damage Index were 21.56 +/- 15.41 and 134.83
      +/- 94.12, respectively. A strong and statistically significant statistically
      correlation between the two analytical methods was observed (r = 0.95; p < 0.05).
      These results demonstrate that the comet assay is a useful method to detect the
      possible effects of genotoxic agents in loggerhead sea turtle and to increase the
      knowledge about the ecotoxicological health status of this threatened species. 

PMID- 24112744
TI  - Clowning as a supportive measure in paediatrics - a survey of clowns, parents and
      nursing staff.
AB  - BACKGROUND: Hospital clowns, also known as clown doctors, can help paediatric
      patients with the stress of a hospitalization and to circumvent the accompanying
      feelings of fear, helplessness and sadness, thus supporting the healing process.
      The objectives of the present study were to clarify the structural and procedural
      conditions of paediatric clowning in Germany and to document the evaluations of
      hospital clowns, parents and hospital staff. METHODS: A nationwide online survey
      of hospital clowns currently active in paediatric departments and an accompanying
      field evaluation in Hamburg hospitals with surveys of parents and hospital staff
      were conducted. In addition to items developed specifically for the study
      regarding general conditions, procedures, assessments of effects and attitudes,
      the Work Satisfaction Scale was used. The sample included n = 87 hospital clowns,
      37 parents and 43 hospital staff members. RESULTS: The online survey showed that
      the hospital clowns are well-trained, motivated and generally satisfied with
      their work. By their own estimate, they primarily boost morale and promote
      imagination in the patients. However, hospital clowns also desire better
      interdisciplinary collaboration and financial security as well as more
      recognition of their work. The Hamburg field study confirmed the positive results
      of the clown survey. According to the data, a clown intervention boosts morale
      and reduces stress in the patients. Moreover, there are practically no side
      effects. Both parents and hospital staff stated that the patients as well as they
      themselves benefited from the intervention. CONCLUSIONS: The results match those
      of previous studies and give a very positive picture of hospital clowning, so
      that its routine use and expansion thereof can be recommended. Furthermore, the
      intervention should be subject to the rules of evidence-based medicine like other
      medical treatments.

PMID- 24112745
TI  - The changing prevalence of infertility.
AB  - Infertility is a major, multifaceted issue worldwide whose prevalence is
      increasing in both high- and low-income countries. The reasons are numerous, and
      may differ among world regions, but lifestyle and nutritional factors, epidemic
      infections, and sexually transmitted diseases are major determinants in most
      latitudes. Three other reasons may explain the increasing incidence of
      infertility. First, owing to the widespread use of contraception, the choice of
      delaying the first pregnancy until the third decade of life places men and women
      at higher risk for sexually transmitted diseases, and women at higher risk for
      uterine fibroids, endometriosis, polycystic ovary syndrome, and chronic
      anovulation. Second, prolonged exposure to chronic stress and environmental
      pollutants may play a critical role in decreasing fertility. Third, gonadotoxic
      oncologic treatments allow many patients to survive cancer, at the cost of their
      fertility. This consideration may justify the development of treatments that
      preserve fertility. 

PMID- 24112746
TI  - Titrated oral misoprostol solution versus vaginal misoprostol for labor
      induction.
AB  - OBJECTIVE: To determine the efficacy and safety of a titrated oral misoprostol
      solution compared with vaginal misoprostol tablets for labor induction. METHODS:
      A randomized, triple-blind, multicenter clinical trial was conducted between
      March 2010 and June 2011. Women with a single gestation (n=200) were randomized
      to receive a titrated oral misoprostol solution (initial misoprostol dose 20
      MUg/hour; dose increased by 20 MUg/hour every 6 hours up to 80 MUg/hour for a
      maximum of 48 doses) or vaginal misoprostol tablets (25 MUg of misoprostol every
      6 hours for a maximum of 8 doses). Risk ratios (RR) and 95% confidence intervals
      (CIs) were calculated for maternal and perinatal outcomes. RESULTS: The
      frequencies of vaginal delivery not achieved within 12 hours (RR 0.87; 95% CI,
      0.62-1.22) and within 24 hours (RR 1.11; 95% CI, 0.83-1.49) were similar in the 2
      groups. No differences were found in terms of uterine hyperstimulation,
      unfavorable cervix at 12 and 24 hours, oxytocin augmentation, tachysystole,
      epidural analgesia, adverse effects, and perinatal outcome. Approximately 70% of
      the women preferred the oral solution. CONCLUSION: A titrated oral misoprostol
      solution was as effective and safe for labor induction as vaginal misoprostol
      tablets. ClinicalTrial.gov: NCT00 992524.

PMID- 24112747
TI  - Clinical evaluation of peripartum outcomes of mediolateral versus lateral
      episiotomy.
AB  - OBJECTIVE: To evaluate the incidence and extent of vaginal and perineal trauma
      among primiparous women after mediolateral and lateral episiotomy. METHODS: In a
      prospective randomized study at University Hospital Pilsen, Czech Republic, 790
      consecutive primiparous women were enrolled between April 2010 and April 2012.
      Mediolateral episiotomy (MLE) followed an angle of at least 60 degrees  from the
      midline. Lateral episiotomy (LE) started 1-2 cm laterally from the midline and
      was directed toward the ischial tuberosity. A rectal examination was performed
      before episiotomy repair. RESULTS: MLE was performed for 390 women, and LE for
      400. The groups did not differ in maternal or neonatal characteristics. No
      difference was found in incidence or extent of vaginal and perineal trauma; or in
      additional perineal (1.8% vs 1.5%, P=0.6) or vaginal (8.5% vs 10.6%, P=0.2)
      trauma continuing along the episiotomy incision. The incidence of anal sphincter
      injury did not differ between MLE and LE (1.5% vs 1.3%, P=0.7). MLE was
      associated with shorter repair times (P<0.05), less suturing material (P<0.05),
      and shorter distances from the anus (P<0.001). CONCLUSION: Risk of additional
      vaginal and perineal trauma, and anal sphincter injury after adequately performed
      mediolateral episiotomy is relatively low and corresponds to that of lateral
      episiotomy.

PMID- 24112748
TI  - Challenges of identifying stillbirths in community versus facility settings.

PMID- 24112750
TI  - Tropical hemostasis/thrombosis.

PMID- 24112749
TI  - Mid-term results of self-testing of the international normalized ratio in adults
      with a mechanical heart valve.
AB  - BACKGROUND: Commonly the frequency of international normalized ratio (INR)
      monitoring with a conventional laboratory test in stable patients is once a
      month. When using a dedicated personal device for INR assessment, the frequency
      may be increased to two or more times a month. OBJECTIVE: To show that INR
      assessed by self-measurement at home is reliable and feasible in the mid-term and
      improves medical care. PATIENTS AND METHODS: All patients in the study on INR
      self-measurement (clinical trial.gov: NCT00925197), conducted between 2004 and
      2007, were re-contacted for mid-term follow-up. One hundred and seventy eight out
      of 192 patients who participated in the study answered a questionnaire. The
      average follow-up time was 4.2 years (+/-1) for the self-measurement group and
      4.9 years (+/-1) for the laboratory-analyzed control group. RESULTS: Only 26
      patients (group A) continued to use INR self-measurement to monitor treatment
      with vitamin K antagonists (VKA). The main reasons to stop INR self-measurement
      were its high cost and difficulty in obtaining strips. There were significantly
      fewer bleeding complications (p=0.04) and complications related to VKA (p=0.01)
      in self-measured patients compared to the control group. Feelings of security and
      quality of life were also significantly better (p=0.002) for self-measured
      patients. CONCLUSION: Many patients with a mechanical heart valve, who self
      measured INR, continue to use this method for their follow-up because of its
      positive effects on their health and quality of life.

PMID- 24112751
TI  - CRUSADE bleeding risk score validation for ST-segment-elevation myocardial
      infarction undergoing primary percutaneous coronary intervention.
AB  - INTRODUCTION: The CRUSADE bleeding risk score (CBRS) accurately predicts major
      bleeding in non-ST segment elevation myocardial infarction NSTEMI patients.
      However, little information exists about its application in ST segment elevation
      myocardial infarction STEMI. We aimed to assess the ability of CBRS to predict in
      hospital major bleeding in STEMI patients undergoing primary percutaneous
      coronary intervention (PPCI). MATERIALS AND METHODS: We prospectively analyzed
      consecutive STEMI patients undergoing PPCI. Baseline characteristics, in-hospital
      complications and mid term mortality were recorded. Major bleeding was defined by
      the CRUSADE definition. Predictive ability of the CBRS was assessed by logistic
      regression method and the area under the ROC curve (AUC). RESULTS: We included
      1064 patients (mean age 63years). Mean CBRS value was 24. Most of patients
      (740/1064 (69.6%)) were in the two lowest risk quintiles of CBRS. Incidence of in
      hospital major bleeding was 33/1064 (3.1%). The rates of in-hospital bleeding
      across the quintiles of risk groups were 0.4% (very low risk), 2.6% (low), 4.6%
      (moderate), 7.2% (high), and 13.4% (very high) (p 0.001). AUC was 0.80 (95% CI
      0.73-0.87 p 0.001). In patients with radial access angiography (n=621) AUC was
      0.81 (95% CI: 0.65-0.97). Mean follow up was 344days. Patients with bleeding
      events had higher mortality during follow up (HR 6.91; 95% CI 3.72-12.82; p
      0.001). CONCLUSIONS: Our patients had a significantly lower bleeding risk as
      compared to CRUSADE NSTEMI population. CBRS accurately predicted major in
      hospital bleeding in this different clinical scenario, including patients with
      radial artery approach.

PMID- 24112752
TI  - Antifibrinolytic thereapy.

PMID- 24112753
TI  - Anticoagulation duration in heterozygous factor V Leiden: a decision analysis.
AB  - BACKGROUND: Current anticoagulation guidelines suggest that optimal
      anticoagulation duration for unprovoked venous thromboembolism is determined by
      an individual risk assessment, balancing risks of anticoagulation bleeding with
      venous thromboembolism recurrence. Among individuals heterozygous for the factor
      V Leiden mutation, while venous thromboembolism recurrence risk is greater, the
      risk for bleeding is recognized to be lower, suggesting longer duration
      anticoagulation could be considered. OBJECTIVE: The objective of this study was
      to compare standard vs. lifelong anticoagulation in 20-year-old factor V Leiden
      heterozygotes with unprovoked venous thromboembolism. METHODS: A Markov state
      transition model was used, incorporating risks of major, minor, and fatal
      anticoagulation bleeding, bleeding and thromboembolism morbidity and mortality,
      and quality of life utilities. Model parameter values favoring lifelong
      anticoagulation in factor V Leiden heterozygotes were determined in sensitivity
      analyses. Outcomes were in quality-adjusted life years, discounted at 3% per
      year. RESULTS: In general population groups with odds ratios for venous
      thromboembolism recurrence and anticoagulation bleeding of 1.0, a short-term
      anticoagulation strategy gained 0.09 quality-adjusted life years more than a
      lifelong anticoagulation strategy. By contrast, in factor V Leiden heterozygotes,
      lifetime anticoagulation was favored if their relative risk of venous
      thromboembolism was greater than 1.07 or their relative risk for bleeding was
      less than 0.91. Results were relatively insensitive to individual variation in
      other parameter values. CONCLUSION: Lifelong anticoagulation may benefit
      individuals heterozygous for factor V Leiden and previous idiopathic venous
      thromboembolism. Studies assessing bleeding risk with anticoagulation in factor V
      Leiden heterozygotes and the costs of indefinite anticoagulation are needed to
      determine if lifelong anticoagulation is the optimal strategy.

PMID- 24112754
TI  - Is 1H NMR metabolomics becoming the promising early biomarker for neonatal sepsis
      and for monitoring the antibiotic toxicity?
AB  - Metabolomics, the latest of omics disciplines, has been successfully used in
      various fields of basic research such as pharmacology and toxicology. Recently,
      this new science has gained an important role in the translational research of
      diagnostics. In this regard, the challenge for neonatologists and medical
      laboratories is to diagnose neonatal sepsis, a disease with high mortality and
      morbidity due to the difficulty in diagnosing it. Metabolomics, through its
      ability to identify perturbations caused by this condition, aims at recognizing
      metabolites that characterize neonatal sepsis with high specificity and
      sensitivity. The purpose of this review is to highlight the ability of
      metabolomics to find early biomarkers for this condition, as well as to predict
      the toxic effects caused by antibiotics. 

PMID- 24112755
TI  - Antiviral efficacy of entecavir in nucleos(t)ide-naive patients of Black/African
      descent with chronic hepatitis B.
AB  - This single-arm, open-label, descriptive study assessed the efficacy and safety
      of entecavir (ETV) in nucleos(t)ide-naive Black/African American patients with
      chronic hepatitis B (CHB), a patient population underrepresented in ETV
      registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of
      self-described Black/African American race received ETV 0.5 mg daily for 52
      weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%,
      noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50
      IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%)
      were high, possibly due to the high HBV genotype A prevalence (70%). No patient
      experienced virological breakthrough. Samples for resistance testing were
      available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment
      visit. No ETV resistance was detected. The safety profile of ETV was consistent
      with that observed in ETV registration trials. This study shows that in
      Black/African American patients with CHB, ETV was well tolerated and demonstrated
      comparable antiviral efficacy to that observed in White and Asian patients in ETV
      Phase III studies. 

PMID- 24112756
TI  - A test method for quantification of stimulus-induced depression effects on
      perceptual threshold in epiretinal prosthesis.
AB  - PURPOSE: As part of a clinical trial, an investigational epiretinal implant (IMI
      Intelligent Medical Implant) was implanted in a retinitis pigmentosa patient. The
      prosthesis was wirelessly controlled by a visual interface containing a
      microcamera, providing wireless data and energy transmission. Forty-nine (49)
      electrodes were used for pattern recognition. This study examined the changes of
      perceptual thresholds over time and its relation to long-term stimulation. The
      goal of the study was to introduce stimulus-related depression of perceptual
      threshold (StirDepth) measurements as a method to gain further insight into the
      safety profile of electrical stimulation. METHODS: The perceptual threshold was
      defined as the level of stimulation intensity at which a phosphene perception
      with a probability of 50% was detected using the Best-PEST method. StirDepth was
      measured by comparing the threshold changes immediately before and after a
      stimulation session of using three active electrodes and one passive electrode,
      which served as control. RESULTS: The initial threshold of the day remained
      stable over the observed period. In StirDepth measurement all thresholds raised
      significantly after the stimulation sessions. The threshold increase of the
      active electrodes never exceeded that of the inactive control electrode.
      CONCLUSIONS: StirDepth measurement is feasible in epiretinal implants. The
      prolonged stimulation raised no safety concerns in the patient. The threshold
      increase of both the active electrodes and the control electrode leads one to
      hypothesise that cognitive or neurophysiological effects are the cause rather
      than the desensitizing of the retinal network or incipient retinal damage.

PMID- 24112757
TI  - Rust disease of eucalypts, caused by Puccinia psidii, did not originate via host
      jump from guava in Brazil.
AB  - The rust fungus, Puccinia psidii, is a devastating pathogen of introduced
      eucalypts (Eucalyptus spp.) in Brazil where it was first observed in 1912. This
      pathogen is hypothesized to be endemic to South and Central America and to have
      first infected eucalypts via a host jump from native guava (Psidium guajava). Ten
      microsatellite markers were used to genotype 148 P. psidii samples from eucalypts
      and guava plus five additional myrtaceous hosts across a wide geographic range of
      south-eastern Brazil and Uruguay. Principal coordinates analysis, a Bayesian
      clustering analysis and a minimum-spanning network revealed two major genetic
      clusters among the sampled isolates, one associated with guava and another
      associated with eucalypts and three additional hosts. Multilocus genotypes
      infecting guava differed by multiple mutational steps at eight loci compared with
      those infecting eucalypts. Approximate Bayesian computation revealed that
      evolutionary scenarios involving a coalescence event between guava- and eucalypt
      associated pathogen populations within the past 1000 years are highly unlikely.
      None of the analyses supported the hypothesis that eucalypt-infecting P. psidii
      in Brazil originated via host jump from guava following the introduction of
      eucalypts to Brazil approximately 185 years ago. The existence of host-associated
      biotypes of P. psidii in Brazil indicates that this diversity must be considered
      when assessing the invasive threat posed by this pathogen to myrtaceous hosts
      worldwide. 

PMID- 24112758
TI  - Onychomatricoma has channel-like structures on in vivo reflectance confocal
      microscopy.
AB  - BACKGROUND: Onychomatricoma is a benign fibroepithelial nail matrix tumor that
      infiltrates the nail plate leading to multiple tunneled cavities lined with
      matrix epithelium and filled with serum. Diagnostic features of onychomatricoma
      on reflectance confocal microscopy (RCM) have not been previously described.
      OBJECTIVE: We sought to demonstrate the feasibility of using RCM to diagnose
      onychomatricoma. METHODS: Reflectance confocal microscopy was used to evaluate
      four patients with onychomatricoma before tumor excision. We evaluated the
      affected nail and one unaffected nail of each patient with VivaScope 1500 (Lucid
      Inc., Rochester, NY, USA). RESULTS: Reflectance confocal microscopy evaluation of
      onychomatricomas revealed longitudinal dark areas and bright/grey lines, forming
      channel like structures. The channels were outlined by bright circular lines with
      grey dot centers. These RCM features correlated with the pathology of the
      onychomatricomas within the nail plate. LIMITATIONS: Proximal portion of
      onychomatricoma was not reach by RCM. CONCLUSIONS: Reflectance confocal
      microscopy can assist in rapid and noninvasive diagnosis of onychomatricoma
      showing characteristic channel like structures within nail plates.

PMID- 24112759
TI  - Pharyngolaryngeal zoster: indeed challenging, but also dreadful.

PMID- 24112760
TI  - HPV-related oropharyngeal squamous cell carcinomas: a comparison between three
      diagnostic approaches.
AB  - PURPOSE: HPV-related oropharyngeal squamous cell carcinomas clearly represent a
      growing entity in the head and neck with distinct carcinogenesis, clinico
      pathological presentation and survival profile. We aimed to compare the HPV
      prevalence rates and clinico-pathological correlations obtained with three
      distinct commonly used HPV detection methods. MATERIALS AND METHODS: p16
      immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV
      genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were
      performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46
      patients treated for single primary oropharyngeal carcinomas. RESULTS: Twenty
      eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%)
      harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO
      LiPA. The concordance analysis revealed a good agreement between both HPV DNA
      detection methods (kappa=0.65); when both tests were positive, the depicted HPV
      subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement
      was moderate between IHC and qPCR (kappa=0.59) and fair between IHC and INNO-LiPA
      (kappa=0.22). CONCLUSIONS: Certain highly sensitive methods are able to detect
      the mere presence of HPV without any carcinogenetic involvement while other more
      specific tests provide proof of viral transcriptional activity and thus evidence
      of clinically relevant infections. The use of a stepwise approach allows reducing
      false positives; p16-immunostaining seems to be an excellent screening test and
      in situ hybridization may overcome some of the PCR limitations.

PMID- 24112761
TI  - Cochlear implantation in 13q deletion syndrome.
AB  - PURPOSE: The advent of cochlear implantation has been followed by an explosion in
      surgical and technological advances with subsequent alterations in the treatment
      of sensorineural hearing loss management. Many individuals with rare genetic
      abnormalities who once may have not been considered candidates for cochlear
      implantation are now benefiting from cochlear implantation. One of these unusual
      syndromes is the 13q deletion syndrome. The clinical features of 13q deletion
      syndrome, a rare chromosomal abnormality, were originally described in the early
      1960s, though the literature currently lacks defined phenotypic abnormalities.
      Patients with 13q deletion syndrome present with varying degrees of cognitive and
      growth delay, craniofacial dysmorphisms, and congenital malformations. The
      etiology of the sensorineural hearing loss has not been elucidated, and genes
      associated with other syndromes which include sensorineural hearing loss have
      been proposed as the causative agents. We describe the unique clinical and
      surgical considerations for 13q deletion syndrome and review the considerations
      when deliberating on cochlear implantation in syndromic hearing loss. MATERIALS
      AND METHODS: Case report. RESULTS: Successful cochlear implantation in a patient
      with 13q deletion syndrome. CONCLUSION: Many patients with 13q deletion syndrome
      suffer from sensorineural hearing loss, and when appropriately selected may
      likely benefit from cochlear implantation. Many other syndromic patients
      following careful selection may also benefit from cochlear implantation and
      should not be excluded from consideration until appropriately evaluated.

PMID- 24112762
TI  - Metal-sensitive and thermostable trypsin from the crevalle jack (Caranx hippos)
      pyloric caeca: purification and characterization.
AB  - BACKGROUND: Over the past decades, the economic development and world population
      growth has led to increased for food demand. Increasing the fish production is
      considered one of the alternatives to meet the increased food demand, but the
      processing of fish leads to by-products such as skin, bones and viscera, a source
      of environmental contamination. Fish viscera have been reported as an important
      source of digestive proteases with interesting characteristics for
      biotechnological processes. Thus, the aim of this study was to purify and to
      characterize a trypsin from the processing by-products of crevalle jack (Caranx
      hippos) fish. RESULTS: A 27.5 kDa trypsin with N-terminal amino acid sequence
      IVGGFECTPHVFAYQ was easily purified from the pyloric caeca of the crevalle jack.
      Its physicochemical and kinetic properties were evaluated using N-alpha-benzoyl
      DL-arginine-p-nitroanilide (BApNA) as substrate. In addition, the effects of
      various metal ions and specific protease inhibitors on trypsin activity were
      determined. Optimum pH and temperature were 8.0 and 50 degrees C, respectively.
      After incubation at 50 degrees C for 30 min the enzyme lost only 20% of its
      activity. Km, kcat, and kcat/Km values using BApNA as substrate were 0.689 mM,
      6.9 s-1, and 10 s-1 mM-1, respectively. High inhibition of trypsin activity was
      observed after incubation with Cd2+, Al3+, Zn2+, Cu2+, Pb2+, and Hg2+ at 1 mM,
      revealing high sensitivity of the enzyme to metal ions. CONCLUSIONS: Extraction
      of a thermostable trypsin from by-products of the fishery industry confirms the
      potential of these materials as an alternative source of these biomolecules.
      Furthermore, the results suggest that this trypsin-like enzyme presents
      interesting biotechnological properties for industrial applications.

PMID- 24112763
TI  - Sample entropy characteristics of movement for four foot types based on plantar
      centre of pressure during stance phase.
AB  - BACKGROUND: Motion characteristics of CoP (Centre of Pressure, the point of
      application of the resultant ground reaction force acting on the plate) are
      useful for foot type characteristics detection. To date, only few studies have
      investigated the nonlinear characteristics of CoP velocity and acceleration
      during the stance phase. The aim of this study is to investigate whether CoP
      regularity is different among four foot types (normal foot, pes valgus, hallux
      valgus and pes cavus); this might be useful for classification and diagnosis of
      foot injuries and diseases. To meet this goal, sample entropy, a measure of time
      series regularity, was used to quantify the CoP regularity of four foot types.
      METHODS: One hundred and sixty five subjects that had the same foot type
      bilaterally (48 subjects with healthy feet, 22 with pes valgus, 47 with hallux
      valgus, and 48 with pes cavus) were recruited for this study. A Footscan(r)
      system was used to collect CoP data when each subject walked at normal and steady
      speed. The velocity and acceleration in medial-lateral (ML) and anterior
      posterior (AP) directions, and resultant velocity and acceleration were derived
      from CoP. The sample entropy is the negative natural logarithm of the conditional
      probability that a subseries of length m that matches pointwise within a
      tolerance r also matches at the next point. This was used to quantify variables
      of CoP velocity and acceleration of four foot types. The parameters r (the
      tolerance) and m (the matching length) for sample entropy calculation have been
      determined by an optimal method. RESULTS: It has been found that in order to
      analyze all CoP parameters of velocity and acceleration during the stance phase
      of walking gait, for each variable there is a different optimal r value. On the
      contrary, the value m=4 is optimal for all variables.Sample entropies of both
      velocity and acceleration in AP direction were highly correlated with their
      corresponding resultant variables for r>0.91. The sample entropy of the velocity
      in AP direction was moderately correlated with the one of the acceleration in the
      same direction (r>=0.673), as well as with the resultant acceleration (r>=0.660).
      The sample entropy of resultant velocity was moderately correlated with the one
      of the acceleration in AP direction, as well as with the resultant acceleration
      (for the both r>=0.689). Moderate correlations were found between variables for
      the left foot and their corresponding variables for the right foot.Sample
      entropies of AP velocity, resultant velocity, AP acceleration, and resultant
      acceleration of the right foot as well as AP velocity and resultant velocity of
      the left foot were, respectively, significantly different among the four foot
      types. CONCLUSIONS: It can be concluded that the sample entropy of AP velocity
      (or the resultant velocity) of the left foot, ML velocity, resultant velocity, ML
      acceleration and resultant acceleration could serve for evaluation of foot types
      or selection of appropriate footwear.

PMID- 24112764
TI  - Skin temperature over the carotid artery provides an accurate noninvasive
      estimation of core temperature in infants and young children during general
      anesthesia.
AB  - BACKGROUND: The accurate measurement of core temperature is an essential aspect
      of intraoperative management in children. Invasive measurement sites are accurate
      but carry some health risks and cannot be used in certain patients. An accurate
      form of noninvasive thermometry is therefore needed. Our aim was to develop, and
      subsequently validate, separate models for estimating core temperature using
      different skin temperatures with an individualized correction factor. METHODS:
      Forty-eight pediatric patients (0-36 months) undergoing elective surgery were
      separated into a modeling group (MG, n = 28) and validation group (VG, n = 20).
      Skin temperature was measured over the carotid artery (Tsk_carotid ), upper
      abdomen (Tsk_abd ), and axilla (Tsk_axilla ), while nasopharyngeal temperature
      (Tnaso ) was measured as a reference. RESULTS: In the MG, derived models for
      estimating Tnaso were: Tsk_carotid  + 0.52; Tsk_abd  + (0.076[body mass] + 0.02);
      and Tsk_axilla  + (0.081[body mass]-0.66). After adjusting raw Tsk_carotid,
      Tsk_abd , and Tsk_axilla values in the independent VG using these models, the
      mean bias (Predicted Tnaso - Actual Tnaso [with 95% confidence intervals]) was
      +0.03[+0.53, -0.50] degrees C, -0.05[+1.02, -1.07] degrees C, and -0.06[+1.21, 
      1.28 degrees C], respectively. The percentage of values within +/-0.5 degrees C
      of Tnaso was 93.2%, 75.4%, and 66.1% for Tsk_carotid, Tsk_abd , and Tsk_axilla ,
      respectively. Sensitivity and specificity for detecting hypothermia (Tnaso  <
      36.0 degrees C) was 0.88 and 0.91 for Tsk_carotid , 0.61 and 0.76 for Tsk_abd ,
      and 0.91 and 0.73 for Tsk_axilla . Goodness-of-fit (R(2) ) relative to the line
      of-identity was 0.74 (Tsk_carotid ), 0.34 (Tsk_abd ), and 0.15 (Tsk_axilla ).
      CONCLUSIONS: Skin temperature over the carotid artery, with a simple correction
      factor of +0.52 degrees C, provides a viable noninvasive estimate of Tnaso in
      young children during elective surgery with a general anesthetic.

PMID- 24112765
TI  - Male-sterile maize plants produced by targeted mutagenesis of the cytochrome P450
      like gene (MS26) using a re-designed I-CreI homing endonuclease.
AB  - The I-CreI homing endonuclease from Chlamydomonas reinhardti has been used as a
      molecular tool for creating DNA double-strand breaks and enhancing DNA
      recombination reactions in maize cells. The DNA-binding properties of this
      protein were re-designed to recognize a 22 bp target sequence in the 5th exon of
      MS26, a maize fertility gene. Three versions of a single-chain endonuclease,
      called Ems26, Ems26+ and Ems26++, cleaved their intended DNA site within the
      context of a reporter assay in a mammalian cell line. When the Ems26++ version
      was delivered to maize Black Mexican Sweet cells by Agrobacterium-mediated
      transformation, the cleavage resulted in mutations at a co-delivered extra
      chromosomal ms26-site in up to 8.9% of the recovered clones. Delivery of the same
      version of Ems26 to immature embryos resulted in mutations at the predicted
      genomic ms26-site in 5.8% of transgenic T(0) plants. This targeted mutagenesis
      procedure yielded small deletions and insertions at the Ems26 target site
      consistent with products of double-strand break repair generated by non
      homologous end joining. One of 21 mutagenized T(0) plants carried two mutated
      alleles of the MS26 gene. As expected, the bi-allelic mutant T(0) plant and the
      T(1) progeny homozygous for the ms26 mutant alleles were male-sterile. This paper
      described the second maize chromosomal locus (liguless-1 being the first one)
      mutagenized by a re-designed I-CreI-based endonuclease, demonstrating the general
      utility of these molecules for targeted mutagenesis in plants.

PMID- 24112766
TI  - Neoadjuvant radiation therapy and its impact on complications after
      pancreaticoduodenectomy for pancreatic cancer: analysis of the American College
      of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).
AB  - OBJECTIVES: This study investigated the impact of neoadjuvant radiation therapy
      (XRT) on postoperative outcomes following pancreaticoduodenectomy for pancreatic
      cancer. METHODS: The American College of Surgeons National Quality Improvement
      Program database was queried for the period 2005-2010 to assess complication
      rates following pancreaticoduodenectomy for pancreatic cancer. Two groups of
      patients were identified, comprising those who received neoadjuvant XRT and those
      who did not (control group). RESULTS: A total of 4416 patients were identified,
      including 200 in the XRT group and 4216 in the control group. There were
      differences in patient characteristics between the groups, including in age,
      hypertension and bilirubin level. Despite the fact that weight loss was more
      common, median operative time was longer (423 min versus 368 min; P < 0.001), and
      vascular reconstruction was more commonly required (20.5% versus 8.4%; P < 0.001)
      in the XRT group. In addition, the XRT group had a shorter median hospital stay
      than the control group (9 days versus 10 days; P = 0.005). Mortality (3.0% versus
      2.7%; P = 0.818) and morbidity (40.5% versus 37.6%; P = 0.404) rates were not
      influenced by neoadjuvant XRT. Blood transfusion rates were increased in the XRT
      group (13.0% versus 7.4%; P = 0.003). Severe complications were influenced by age
      >70 years, American Society of Anesthesiologists (ASA) class >2, preoperative
      sepsis, dyspnoea, weight loss, impaired functional status, peripheral vascular
      disease and operative time of >8 h. CONCLUSIONS: Neoadjuvant XRT is not
      associated with an increase in complications after pancreaticoduodenectomy.

PMID- 24112767
TI  - Poly-L-glutamate/glutamine synthesis in the cell wall of Mycobacterium bovis is
      regulated in response to nitrogen availability.
AB  - BACKGROUND: The cell wall of pathogenic mycobacteria is known to possess poly-L
      glutamine (PLG) layer. PLG synthesis has been directly linked to glutamine
      synthetase (GS) enzyme. glnA1 gene encodes for GS enzyme in mycobacteria. PLG
      layer is absent in cell wall of avirulent Mycobacterium smegmatis, although M.
      smegmatis strain expressing GS enzyme of pathogenic mycobacteria can synthesize
      PLG layer in the cell wall. The role of GS enzyme has been extensively studied in
      Mycobacterium tuberculosis, however, little is known about GS enzyme in other
      mycobacterial species. Mycobacterium bovis, as an intracellular pathogen
      encounters nitrogen stress inside macrophages, thus it has developed nitrogen
      assimilatory pathways to survive in adverse conditions. We have investigated the
      expression and activity of M. bovis GS in response to nitrogen availability and
      effect on synthesis of PLG layer in the cell wall. M. smegmatis was used as a
      model to study the behaviour of glnA1 locus of M. bovis. RESULTS: We observed
      that GS expression and activity decreased significantly in high nitrogen grown
      conditions. In high nitrogen conditions, the amount of PLG in cell wall was
      drastically reduced (below detectable limits) as compared to low nitrogen
      condition in M. bovis and in M. smegmatis strain complemented with M. bovis
      glnA1. Additionally, biofilm formation by M. smegmatis strain complemented with
      M. bovis glnA1 was increased than the wild type M. smegmatis strain. CONCLUSIONS:
      The physiological regulation of GS in M. bovis was found to be similar to that
      reported in other mycobacteria but this data revealed that PLG synthesis in the
      cell wall of pathogenic mycobacteria occurs only in nitrogen limiting conditions
      and on the contrary high nitrogen conditions inhibit PLG synthesis. This
      indicates that PLG synthesis may be a form of nitrogen assimilatory pathway
      during ammonium starvation in virulent mycobacteria. Also, we have found that M.
      smegmatis complemented with M. bovis glnA1 was more efficient in biofilm
      formation than the wild type strain. This indicates that PLG layer favors biofilm
      formation. This study demonstrate that the nitrogen availability not only
      regulates GS expression and activity in M. bovis but also affects cell surface
      properties by modulating synthesis of PLG.

PMID- 24112768
TI  - Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and
      further modified by proton pump inhibitors.
AB  - Gastro-oesophageal reflux can cause inflammation, metaplasia, dysplasia and
      cancer of the oesophagus. Despite the increased use of proton pump inhibitors
      (PPIs) to treat reflux, the incidence of oesophageal adenocarcinoma has increased
      rapidly in Europe and in the United States in the last 25 years. The reasons for
      this increase remain unclear. In this study, we aimed to determine whether the
      microbiota of the gastric refluxate and oesophageal biopsies differs between
      patients with heartburn and normal-appearing oesophageal mucosa versus patients
      with abnormal oesophageal mucosa [oesophagitis or Barrett's oesophagus (BE)] and
      to elucidate the effect of PPIs on the bacterial communities using 16S rRNA gene
      pyrosequencing. Significant differences in the composition of gastric fluid
      bacteria were found between patients with heartburn and normal oesophageal tissue
      versus patients with oesophagitis or BE, but in the oesophagus-associated
      microbiota differences were relatively modest. Notably, increased levels of
      Enterobacteriaceae were observed in the gastric fluid of oesophagitis and BE
      patients. In addition, treatment with PPIs had dramatic effects on microbial
      communities both in the gastric fluids and the oesophageal tissue. In conclusion,
      gastric fluid microbiota is modified in patients with oesophagitis and BE
      compared with heartburn patients with normal biopsies. Furthermore, PPI treatment
      markedly alters gastric and oesophageal microbial populations. Determining
      whether the changes in bacterial composition caused by PPIs are beneficial or
      harmful will require further investigation. 

PMID- 24112769
TI  - Genome-wide analysis and molecular dissection of the SPL gene family in Salvia
      miltiorrhiza.
AB  - SQUAMOSA promoter binding protein-likes (SPLs) are plant-specific transcription
      factors playing vital regulatory roles in plant growth and development. There is
      no information about SPLs in Salvia miltiorrhiza (Danshen), a significant
      medicinal plant widely used in Traditional Chinese medicine (TCM) for >1,700
      years and an emerging model plant for TCM studies. Through genome-wide
      identification and subsequent molecular cloning, we identified a total 15 SmSPLs
      with divergent sequence features, gene structures, and motifs. Comparative
      analysis showed sequence conservation between SmSPLs and their Arabidopsis
      counterparts. A phylogenetic tree clusters SmSPLs into six groups. Many of the
      motifs identified commonly exist in a group/subgroup, implying their functional
      redundancy. Eight SmSPLs were predicted and experimentally validated to be
      targets of miR156/157. SmSPLs were differentially expressed in various tissues of
      S. milltiorrhiza. The expression of miR156/157-targeted SmSPLs was increased with
      the maturation of S. miltiorrhiza, whereas the expression of miR156/157 was
      decreased, confirming the regulatory roles of miR156/157 in SmSPLs and suggesting
      the functions of SmSPLs in S. miltiorrhiza development. The expression of
      miR156/157 was negatively correlated with miR172 during the maturation of S.
      miltiorrhiza. The results indicate the significance and complexity of SmSPL-,
      miR156-, and miR172-mediated regulation of developmental timing in S.
      miltiorrhiza. 

PMID- 24112770
TI  - Discovering isozyme-selective inhibitor scaffolds of human carbonic anhydrases
      using structural alignment and de novo drug design approaches.
AB  - The development of isozyme-selective carbonic anhydrase inhibitors is currently
      still a great challenge. In the present study, protein-ligand complex structures
      were obtained by AutoDock Vina with SBR ((R)-N-(3-indol-1-yl-2-methyl-propyl)-4
      sulfamoyl-benzamide) as the only inhibitor docked into the binding pockets of
      human isozymes CA I, II, IV, VI, IX, XII, and XIII. To make the spatial
      structures of complexes comparable, the co-ordinates for CA domains were
      reassigned based on structural alignments. With preferred docking poses of SBR
      been reduced to seed structures, the LigBuilder was used to build up inhibitor
      molecules. The results suggested that sulfonamide derivatives with naphthalene,
      fluorene, and acridan as the scaffold structures can be the potential isozyme
      selective CAIs, especially for isozymes CA II, IV, and IX. 

PMID- 24112771
TI  - The ADP-glucose pyrophosphorylase from Streptococcus mutans provides evidence for
      the regulation of polysaccharide biosynthesis in Firmicutes.
AB  - Streptococcus mutans is the leading cause of dental caries worldwide. The
      bacterium accumulates a glycogen-like internal polysaccharide, which mainly
      contributes to its carionegic capacity. S.mutans has two genes (glgC and glgD)
      respectively encoding putative ADP-glucose pyrophosphorylases (ADP-Glc PPase), a
      key enzyme for glycogen synthesis in most bacteria. Herein, we report the
      molecular cloning and recombinant expression of both genes (separately or
      together) followed by the characterization of the respective enzymes. When
      expressed individually GlgC had ADP-Glc PPase activity, whereas GlgD was
      inactive. Interestingly, the coexpressed GlgC/GlgD protein was one order of
      magnitude more active than GlgC alone. Kinetic characterization of GlgC and
      GlgC/GlgD pointed out remarkable differences between them. Fructose-1,6-bis
      phosphate activated GlgC by twofold, but had no effect on GlgC/GlgD. Conversely,
      phospho-enol-pyruvate and inorganic salts inhibited GlgC/GlgD without affecting
      GlgC. However, in the presence of fructose-1,6-bis-phosphate GlgC acquired a
      GlgC/GlgD-like behaviour, becoming sensitive to the stated inhibitors. Results
      indicate that S. mutans ADP-Glc PPase is an allosteric regulatory enzyme
      exhibiting sensitivity to modulation by key intermediates of carbohydrates
      metabolism in the cell. The particular regulatory properties of the S.mutans
      enzyme agree with phylogenetic analysis, where GlgC and GlgD proteins found in
      other Firmicutes arrange in distinctive clusters.

PMID- 24112772
TI  - Insight into the photosynthetic apparatus in evergreen and deciduous European
      oaks during autumn senescence using OJIP fluorescence transient analysis.
AB  - Climate change is one of the major issues nowadays, and Mediterranean broadleaf
      species have been suggested to fill possible future gaps created by climate
      change in Central European forests. To provide a scientific-based foundation for
      such practical strategies, it is important to obtain a general idea about
      differences and similarities in the physiology of Central European and
      Mediterranean species. In the present study, we evaluated the onset of leaf
      senescence of a broad spectrum of oak species under the Central European climate
      in a common garden experiment. Degradation of the photosynthetic apparatus of
      evergreen (Quercus ilex, Q. suber), semi-evergreen (Q.*turneri, Q.*hispanica) and
      deciduous oaks (Q. robur, Q. cerris, Q. frainetto, Q. pubescens) was monitored as
      chlorophyll content and analysed chlorophyll fluorescence induction transients.
      In the deciduous species, a significant decline in chlorophyll content was
      observed during autumn/winter, with Q. pubescens showing the slowest decline.
      Analysis of fluorescence induction transients revealed a significant decline in
      quantum efficiency of the primary photochemistry and reaction centre density and
      later, a decrease in quantum efficiency of end acceptor reduction. Alterations in
      fluorescence parameters were compared to the decline in chlorophyll content,
      which occurred much more slowly than expected from the fluorescence data. The
      evergreen species showed no decline in chlorophyll content, nor different
      chlorophyll a fluorescence induction behaviour despite temperature falling below
      0  degrees C. The hybrids showed intermediate behaviour between their parental
      evergreen and deciduous taxa.

PMID- 24112773
TI  - A robust prognostic signature for hormone-positive node-negative breast cancer.
AB  - BACKGROUND: Systemic chemotherapy in the adjuvant setting can cure breast cancer
      in some patients that would otherwise recur with incurable, metastatic disease.
      However, since only a fraction of patients would have recurrence after surgery
      alone, the challenge is to stratify high-risk patients (who stand to benefit from
      systemic chemotherapy) from low-risk patients (who can safely be spared treatment
      related toxicities and costs). METHODS: We focus here on risk stratification in
      node-negative, ER-positive, HER2-negative breast cancer. We use a large database
      of publicly available microarray datasets to build a random forests classifier
      and develop a robust multi-gene mRNA transcription-based predictor of relapse
      free survival at 10 years, which we call the Random Forests Relapse Score (RFRS).
      Performance was assessed by internal cross-validation, multiple independent data
      sets, and comparison to existing algorithms using receiver-operating
      characteristic and Kaplan-Meier survival analysis. Internal redundancy of
      features was determined using k-means clustering to define optimal signatures
      with smaller numbers of primary genes, each with multiple alternates. RESULTS:
      Internal OOB cross-validation for the initial (full-gene-set) model on training
      data reported an ROC AUC of 0.704, which was comparable to or better than those
      reported previously or obtained by applying existing methods to our dataset.
      Three risk groups with probability cutoffs for low, intermediate, and high-risk
      were defined. Survival analysis determined a highly significant difference in
      relapse rate between these risk groups. Validation of the models against
      independent test datasets showed highly similar results. Smaller 17-gene and 8
      gene optimized models were also developed with minimal reduction in performance.
      Furthermore, the signature was shown to be almost equally effective on both
      hormone-treated and untreated patients. CONCLUSIONS: RFRS allows flexibility in
      both the number and identity of genes utilized from thousands to as few as 17 or
      eight genes, each with multiple alternatives. The RFRS reports a probability
      score strongly correlated with risk of relapse. This score could therefore be
      used to assign systemic chemotherapy specifically to those high-risk patients
      most likely to benefit from further treatment.

PMID- 24112774
TI  - Do the coach and athlete have the same "picture" of the situation? Distributed
      Situation Awareness in an elite sport context.
AB  - Athletes and their coach interpret the training situations differently and this
      can have important implications for the development of an elite athlete's
      performance. It is argued that, from a schema-theoretic perspective, the
      difference in these interpretations needs to be better understood. A post
      performance, self-confrontation, interview was conducted with a number of
      athletes and their coaches. The interviews revealed differences between the
      athlete and their coach in the information they are aware of. In comparison with
      athletes, coaches more frequently compared the phenotype with genotype schemata
      rather than just describing the phenotype schemata. Results suggest SA
      information elements showed some common ground but also revealed some important
      differences between the athlete and coach. The awareness was directed externally
      towards the environment and internally, towards the individual, depending on
      his/her role. The investigation showed that the schemata used to 'frame' the
      information elements were different, but compatible, between athlete and coach. 

PMID- 24112775
TI  - Frequency and duration of nursing care related to older patient mobility.
AB  - PURPOSE: To evaluate the frequency and duration of nursing care activity related
      to mobilizing older patients in acute care settings and determining who initiates
      the mobility event (patient or nurse). METHODS: This was an observation study
      using time and motion. Observers shadowed 15 registered nurses (RNs) each for two
      to three 8-hr periods using hand-held computer tablets to collect data on
      frequency and duration of six mobility events (standing, transferring, walking to
      and from the patient bathroom, walking in the patient room, and walking in the
      hallway) that occurred in the nurse's presence. Chart reviews were conducted on
      47 adult patients (> 65 years of age) who were cared for by the nurses during the
      observation periods. Descriptive statistics (mean, median, standard deviation,
      frequency, and proportion) were used to describe the occurrence of mobility
      events among all 47 patients and among a subgroup of 16 patients identified as
      dependent (needing human assistance of another to ambulate) at the time of
      admission. RESULTS: Thirty-two percent of older patients were not engaged by an
      RN in any mobility event during an 8-hr period. For all patients, standing and
      transferring were the most frequent mobility activity. Mean duration for
      ambulation was less than 2 min per observation period. Patients who were
      dependent had fewer mobility events with no events related to ambulation
      initiated by nurses. The majority of mobility events were initiated by patients.
      CONCLUSIONS: Nurses infrequently initiated mobility events for hospitalized older
      patients and most often engaged patients in low-level activity (standing and
      transferring). CLINICAL RELEVANCE: Limited mobility (standing and transferring
      only) is an independent predictor of negative outcomes for hospitalized older
      patients. Nurses are in a key position to improve outcomes for hospitalized older
      patients by engaging them in mobility activity, particularly ambulation, but
      further research is needed to determine how best to engage nurses in these
      activities.

PMID- 24112776
TI  - Cryoablation for locally advanced clinical stage T3 prostate cancer: a report
      from the Cryo-On-Line Database (COLD) Registry.
AB  - OBJECTIVE: To assess the oncological and functional outcomes of primary prostate
      cryoablation for men with clinical stage T3 (cT3) prostate cancer, as although
      radical prostatectomy (RP) or external beam radiotherapy (EBRT) are the standard
      treatments for locally advanced cT3 prostate cancer some patients opt for
      nonextirpative prostate cryoablation instead. PATIENTS AND METHODS: The Cryo-On
      Line Database (COLD) Registry was queried to identify patients with cT3 prostate
      cancer treated with whole-gland cryoablation (366 patients). We assessed
      biochemical disease-free survival (bDFS) using the Phoenix definition and
      determined reported rates of urinary incontinence and retention, sexual activity,
      and rectourethral fistulisation after treatment. Patients were subsequently
      assessed according to whether they were administered neoadjuvant androgen
      deprivation therapy or not (ADT; 115 patients, 31.4%). RESULTS: For the entire
      cohort, the 36- and 60-month bDFS rates were 65.3% and 51.9%, respectively.
      Patients who received neoadjuvant ADT had statistically nonsignificantly higher
      36- and 60-month bDFS rates (68.0% and 55.4%, respectively) than patients who did
      not receive neoadjuvant ADT (55.3% and 36.9%, respectively). The after treatment
      urinary incontinence rate was 2.6%; urinary retention rate, 6.0%; sexual activity
      rate, 30.4%; and rectourethral fistulisation rate, 1.1%. CONCLUSIONS:
      Cryoablation for patients with cT3 prostate cancer leads to less favourable bDFS
      than that after RP or RT for the same group of men. The after treatment
      rectourethral fistulisation rates for patients with cT3 disease are higher than
      in those with organ-confined prostate cancer treated with cryoablation; however,
      urinary dysfunction and sexual activity rates are similar for men with cT3 to
      those reported from this same registry in men with cT2 disease. The addition of
      neoadjuvant ADT (though not studied prospectively here) should be strongly
      considered if a patient with cT3 prostate cancer is to be treated with
      cryoablation.

PMID- 24112777
TI  - An edge-directed interpolation method for fetal spine MR images.
AB  - BACKGROUND: Fetal spinal magnetic resonance imaging (MRI) is a prenatal routine
      for proper assessment of fetus development, especially when suspected spinal
      malformations occur while ultrasound fails to provide details. Limited by
      hardware, fetal spine MR images suffer from its low resolution.High-resolution MR
      images can directly enhance readability and improve diagnosis accuracy. Image
      interpolation for higher resolution is required in clinical situations, while
      many methods fail to preserve edge structures. Edge carries heavy structural
      messages of objects in visual scenes for doctors to detect suspicions, classify
      malformations and make correct diagnosis. Effective interpolation with well
      preserved edge structures is still challenging. METHOD: In this paper, we propose
      an edge-directed interpolation (EDI) method and apply it on a group of fetal
      spine MR images to evaluate its feasibility and performance. This method takes
      edge messages from Canny edge detector to guide further pixel modification.
      First, low-resolution (LR) images of fetal spine are interpolated into high
      resolution (HR) images with targeted factor by bi-linear method. Then edge
      information from LR and HR images is put into a twofold strategy to sharpen or
      soften edge structures. Finally a HR image with well-preserved edge structures is
      generated. The HR images obtained from proposed method are validated and compared
      with that from other four EDI methods. Performances are evaluated from six
      metrics, and subjective analysis of visual quality is based on regions of
      interest (ROI). RESULTS: All these five EDI methods are able to generate HR
      images with enriched details. From quantitative analysis of six metrics, the
      proposed method outperforms the other four from signal-to-noise ratio (SNR), peak
      signal-to-noise ratio (PSNR), structure similarity index (SSIM), feature
      similarity index (FSIM) and mutual information (MI) with seconds-level time
      consumptions (TC). Visual analysis of ROI shows that the proposed method
      maintains better consistency in edge structures with the original images.
      CONCLUSIONS: The proposed method classifies edge orientations into four
      categories and well preserves structures. It generates convincing HR images with
      fine details and is suitable in real-time situations. Iterative curvature-based
      interpolation (ICBI) method may result in crisper edges, while the other three
      methods are sensitive to noise and artifacts.

PMID- 24112778
TI  - Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance
      in HIV-/HBV-coinfected patients.
AB  - The aim of this retrospective study was the identification of clinically useful
      viral determinants for the prediction of hepatitis B surface antigen (HBsAg)
      seroclearance and sustained virological response in hepatitis B virus/human
      immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active
      combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV
      DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV
      coinfected patients was performed. Calculations of receiver operating
      characteristics (ROC) and Kaplan-Meier analysis were used for the identification
      of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and
      HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on
      treatment decline >= 1 log IU/mL per year achieved higher HBsAg loss rates (P =
      0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg
      seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of
      HBsAg <= 100 IU/mL was highly predictive for HBsAg seroclearance. No significant
      influence of the HBV genotype on HBsAg seroclearance was observed among the
      entire cohort. Quantitative determination of HBsAg provides a clinically useful
      viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and
      HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART.

PMID- 24112779
TI  - Hypoxia-induced downregulation of miR-30c promotes epithelial-mesenchymal
      transition in human renal cell carcinoma.
AB  - MicroRNAs (miRNAs), which negatively regulate protein expression by binding
      protein-coding mRNAs, have been integrated into cancer development and
      progression as either oncogenes or tumor suppressor genes. miR-30c was reported
      to be downregulated in several types of cancer. However, its role in human renal
      cell carcinoma (RCC) remains largely unknown. Here, we show that miR-30c is
      significantly downregulated in human RCC tissues and cell lines. We found that
      miR-30c downregulation could be induced by hypoxia in RCC cells in a hypoxia
      inducible factors (HIFs) dependent manner. Repression of miR-30c through its
      inhibitor resulted in reduction of E-cadherin production and promotion of
      epithelial-mesenchymal transition (EMT), while overexpression of miR-30c
      inhibited EMT in RCC cells. We identified Slug as a direct target of miR-30c in
      RCC cells. Slug was upregulated in RCC tissues and its expression could be
      induced by hypoxia, which is consistent with downregulation of miR-30c by
      hypoxia. Forced overexpression of Slug in 786-O cells reduced E-cadherin
      production, and promoted EMT as well as cell migration. Moreover, Slug
      overexpression abrogated the inhibitory role of miR-30c in regulating EMT and
      cell migration, indicating miR-30c regulates EMT through Slug in RCC cells. Our
      findings propose a model that hypoxia induces EMT in RCC cells through
      downregulation of miR-30c, which leads to subsequent increase of Slug expression
      and repression of E-cadherin production, and suggest a potential application of
      miR-30c in RCC treatment. 

PMID- 24112780
TI  - Catheter ablation of atrial fibrillation: to freeze, or not to freeze, that is
      the question.

PMID- 24112781
TI  - Tendon extracellular matrix damage detection and quantification using automated
      edge detection analysis.
AB  - The accumulation of sub-rupture tendon fatigue damage in the extracellular
      matrix, particularly of type I collagen fibrils, is thought to contribute to the
      development of tendinopathy, a chronic and degenerative pathology of tendons.
      Quantitative assessment of collagen fibril alignment is paramount to
      understanding the importance of matrix injury to cellular function and remodeling
      capabilities. This study presents a novel application of edge detection analysis
      to calculate local collagen fibril orientation in tendon. This technique
      incorporates damage segmentation and stratification by severity which will allow
      future analysis of the direct effect of matrix damage severity on the cellular
      and molecular response. 

PMID- 24112782
TI  - A comprehensive experimental study on material properties of human brain tissue.
AB  - A comprehensive study on the biomechanical response of human brain tissue is
      necessary to investigate traumatic brain injury mechanisms. Published brain
      material property studies have been mostly performed under a specific type of
      loading, which is insufficient to develop accurate brain tissue constitutive
      equations. In addition, inconsistent or contradictory data in the literature made
      it impossible for computational model developers to create a single brain
      material model that can fit most, if not all, experimental results. In the
      current study, a total of 240 brain tissue specimens were tested under tension
      (n=72), compression (n=72), and shear (n=96) loading modes at varying strain
      rates. Gray-white matter difference, regional difference, and directional
      difference within white matter were also investigated. Stress-strain
      relationships of human brain tissue were obtained up to 50% of engineering
      strain. Strain rate dependency was observed under all three loading modes. White
      matter was stiffer than gray matter in compression and shear. Corona radiata was
      found to be stiffer than cortex, thalamus, and corpus callosum in tension and
      compression. Directional dependency of white matter was observed under shear
      loading. 

PMID- 24112783
TI  - Relationship between frequent swimming pool use and lacrimal duct obstruction.

PMID- 24112784
TI  - Synthetic nucleases for genome engineering in plants: prospects for a bright
      future.
AB  - By inducing double-strand breaks (DSB), it is possible to initiate DNA
      recombination. For a long time, it was not possible to use DSB induction for
      efficient genome engineering due to the lack of a means to target DSBs to
      specific sites. This limitation was overcome by development of modified
      meganucleases and synthetic DNA-binding domains. Domains derived from zinc-finger
      transcription factors or transcription activator-like effectors may be designed
      to recognize almost any DNA sequence. By fusing these domains to the endonuclease
      domains of a class II restriction enzyme, an active endonuclease dimer may be
      formed that introduces a site-specific DSB. Recent studies demonstrate that gene
      knockouts via non-homologous end joining or gene modification via homologous
      recombination are becoming routine in many plant species. By creating a single
      genomic DSB, complete knockout of a gene, sequence-specific integration of
      foreign DNA or subtle modification of individual amino acids in a specific
      protein domain may be achieved. The induction of two or more DSBs allows complex
      genomic rearrangements such as deletions, inversions or the exchange of
      chromosome arms. The potential for controlled genome engineering in plants is
      tremendous. The recently discovered RNA-based CRISPR/Cas system, a new tool to
      induce multiple DSBs, and sophisticated technical applications, such as the in
      planta gene targeting system, are further steps in this development. At present,
      the focus remains on engineering of single genes; in the future, engineering of
      whole genomes will become an option. 

PMID- 24112785
TI  - Intracranial hypertension presenting with severe visual failure, without
      concurrent headache, in a child with nephrotic syndrome.
AB  - BACKGROUND: Idiopathic intracranial hypertension is a condition typically
      characterised by headache, normal level of consciousness, papilloedema and raised
      cerebrospinal fluid pressure. Children often present with visual loss and
      atypical features of raised pressure, posing a diagnostic and management
      challenge. A range of renal disorders can predispose to developing this raised
      intracranial pressure syndrome. We present a case of severe visual failure in a
      child with nephrotic syndrome, with no headache when elevated pressure was
      proven. In nephrotic syndrome, visual failure related to elevated intracranial
      pressures without concurrent headache symptoms has not been reported previously.
      CASE PRESENTATION: We discuss a 5-year-old Caucasian girl with steroid sensitive
      nephrotic syndrome who went on to become a late non-responder and presented with
      intracranial hypertension. Following initial response to steroids, she had a
      relapse of her nephrotic syndrome; her proteinuria did not resolve on steroid
      treatment, requiring addition of cyclosporine therapy to manage her nephrotic
      syndrome. Three months following this, she presented with visual failure in the
      right eye with bilateral central scotoma and papilloedema. At the time of
      presentation of visual impairment, she was otherwise well, with no symptoms of a
      raised intracranial pressure syndrome or associated systemic illness. Medical
      management was initiated following confirmation of a raised intracranial
      pressure. Her intracranial pressure remained elevated requiring serial
      therapeutic lumbar punctures before some improvement in visual acuity was
      observed. Later in the clinical course, she presented with worsening of her
      visual impairment with further deterioration of the vision in the left eye, again
      associated with elevated intracranial pressure. An urgent surgical cerebrospinal
      fluid diversion procedure was performed. At review, three years after
      presentation our patient has severe visual impairment with no perception of light
      in her right eye and 6/36 Snellen acuity in the left secondary to optic atrophy.
      CONCLUSION: Our case demonstrates the occurrence of intracranial hypertension in
      nephrotic syndrome, highlighting the atypical presentation of severe visual
      failure without concurrent headache at presentation. This demonstrates the
      management complexities and the need for clear guidelines for ophthalmological
      surveillance to aim to reduce permanent visual impairment.

PMID- 24112786
TI  - Lapatinib plus capecitabine for HER2-positive advanced breast cancer: a
      multicentre study of Anatolian Society of Medical Oncology (ASMO).
AB  - Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth
      factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR).
      The present study evaluated the efficacy and tolerability of the combination of
      lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who
      progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total
      of 203 patients with a median age of 48 years (range: 25-82 years) were evaluated
      retrospectively in 11 centres between September 2007 and May 2011. All the
      patients had HER2-positive MBC progressing after trastuzumab and chemotherapy
      including an anthracycline and/or taxane. All patients were treated with the
      combination of lapatinib (1250 mg/day, continuously) and capecitabine (2000
      mg/m(2) on days 1 through 14 of a 21-day cycle). Data on demographics, clinical
      outcome, and toxicity were collected for descriptive analyses. The median follow
      up was 10.7 months (range: 1-40 months). An overall response rate (ORR) of 33.4%
      was achieved including 7 complete responses (CR, 3.4%), 61 partial responses (PR,
      30.0%), and 44 stable disease (37.9%). Clinical benefit rate of 71.3% was
      achieved. Median progression-free survival (PFS) was 7 months (95% CI: 6-10
      months), with a median overall survival (OS) of 15 months (95% CI: 12-18 months).
      The most common side effects were hand-foot syndrome (46.8%), nausea (42.3%),
      fatigue (42.2%), anorexia (38.5%), diarrhea (31.5%), and rash (29.6%). Grade 3-4
      toxicities were identified as hand foot syndrome (7.9%), diarrhea (6.9%), fatigue
      (5.9%), and rash (5.4%). There were no symptomatic cardiac events. Lapatinib and
      capecitabine combination therapy is effective and well tolerated in patients with
      MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline
      therapy, as evidenced by this retrospective evaluation. Toxicity was mild to
      moderate with low grade 3-4 toxicity. 

PMID- 24112787
TI  - Systematic mutational analysis of FBXO7 in a Parkinson's disease population from
      southern Spain.
AB  - Mutations in FBXO7 (PARK15) have been associated with a syndrome characterized by
      early-onset progressive parkinsonism with and without pyramidal tract signs.
      Therefore, our aim was to analyze this gene in a population from southern Spain
      (338 Parkinson's disease [PD] patients and 330 unrelated control subjects) to
      elucidate the potential involvement of FBXO7 in PD pathogenesis. We identified 17
      variants (11 novel), including 10 missense substitutions, 3 synonymous, and 4
      intronic alterations. Six substitutions were described as putatively damaging by
      the bioinformatics tools and 1 intronic variation was described to affect
      splicing. Minor allele frequencies of the highly polymorphic coding single
      nucleotide polymorphisms (SNPs) in PD patients and control subjects were similar.
      All rare variants were heterozygous. No deletions or duplications involving FBXO7
      exons were identified. Our results suggest that the involvement of the FBXO7 gene
      in PD is very rare, at least in this population from southern Spain. 

PMID- 24112788
TI  - Increased pro-nerve growth factor and decreased brain-derived neurotrophic factor
      in non-Alzheimer's disease tauopathies.
AB  - Alterations in the expression and signaling of brain-derived neurotrophic factor
      (BDNF) and the precursor to nerve growth factor (NGF), proNGF, play a role in the
      neuronal and cognitive dysfunction of Alzheimer's disease. Aggregated amyloid
      beta has been shown to down-regulate specific BDNF transcripts in Alzheimer's
      disease, but the role of tau pathology in neurotrophin dysregulation has not been
      investigated. We measured levels of BDNF mRNA and protein using real-time
      quantitative reverse transcription-polymerase chain reaction and enzyme-linked
      immunosorbent assay and proNGF protein using Western blotting in parietal cortex
      of subjects with tauopathies, neurodegenerative diseases exhibiting tau pathology
      without amyloid-beta accumulation. We observed a significant increase in the
      level of proNGF protein in Pick's disease and a significant decrease in BDNF mRNA
      and protein levels in Pick's disease and corticobasal degeneration, but no
      neurotrophin alterations in progressive supranuclear palsy. The decrease in total
      BDNF mRNA levels in these tauopathies was predominantly due to down-regulation of
      transcript IV. These findings implicate tau pathology in neurotrophin
      dysregulation, which may represent a mechanism through which tau confers toxicity
      in Alzheimer's disease and related non-Alzheimer's dementias. 

PMID- 24112789
TI  - Nature of the neurotoxic membrane actions of amyloid-beta on hippocampal neurons
      in Alzheimer's disease.
AB  - The mechanism by which amyloid-beta (Abeta) produces brain dysfunction in
      patients with Alzheimer's disease is largely unknown. According to previous
      studies, Abeta might share perforating properties with gramicidin, a well
      accepted membrane-disrupting peptide. Therefore, we hypothesize that the key
      steps leading to synaptotoxicity by Abeta and gramicidin involve peptide
      aggregation, pore formation, and calcium dysregulation. Here, we show that Abeta
      and gramicidin form aggregates enriched in beta-sheet structures using electron
      microscopy, and Thioflavin and Congo Red staining techniques. Also, we found that
      Abeta and gramicidin display fairly similar actions in hippocampal cell
      membranes, i.e. inducing Ca(2+) entry and synaptoxicity characterized by the loss
      of synaptic proteins and a decrease in neuronal viability. These effects were not
      observed in a Ca(2+) free solution, indicating that both Abeta and gramicidin
      induce neurotoxicity by a Ca(2+)-dependent mechanism. Using combined perforated
      patch clamp and imaging recordings, we found that only Abeta produced a
      perforation that progressed from a small (Cl(-)-selective pore) to a larger
      perforation that allowed the entry of fluorescent molecules. Therefore, based on
      these results, we propose that the perforation at the plasma membrane by Abeta is
      a dynamic process that is critical in producing neurotoxicity similar to that
      found in the brains of AD patients. 

PMID- 24112790
TI  - Aging-related changes in RP3V kisspeptin neurons predate the reduced activation
      of GnRH neurons during the early reproductive decline in female mice.
AB  - Kisspeptin neurons in the rostral periventricular area of the third ventricle
      (RP3V) play a key role in relaying the positive feedback effects of estradiol
      that activate gonadotropin-releasing hormone (GnRH) neurons and drive a surge in
      the GnRH/luteinizing hormone (LH) level. However, the precise role of kisspeptin
      neurons during female reproductive senescence remains unclear. Focusing on middle
      aged intact female mice with irregular estrous cycles, we found a parallel
      decline in c-Fos-positive kisspeptin neurons and c-Fos-positive GnRH neurons at
      the time of the GnRH/LH surge. Furthermore, in kisspeptin neurons, the expression
      of estrogen receptor alpha (ERalpha), but not progesterone receptor (PR),
      decreased with age. Interestingly, some kisspeptin neurons in the RP3V, but none
      of the GnRH neurons in the rostral preoptic area (rPOA), had a characteristic
      cellular senescence in middle-aged mice and old mice. These data suggest that,
      among the groups of neurons involved in reproductive control, the kisspeptin
      neurons in the RP3V are likely among the earliest to undergo aging processes and
      thus participate in initiating the early reproductive decline. 

PMID- 24112791
TI  - Effects of the neurotrophic agent T-817MA on oligomeric amyloid-beta-induced
      deficits in long-term potentiation in the hippocampal CA1 subfield.
AB  - Formation of oligomeric amyloid-beta (oAbeta) is 1 of the most likely causes of
      Alzheimer's disease (AD). We hypothesized that in the early phase of AD,
      cognitive impairments observed before marked neuronal loss and brain atrophy
      might be associated with oAbeta-induced synaptic dysfunction. T-817MA [1-{3-[2-(1
      benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] has both neuroprotective
      and neurotrophic effects and is used to treat AD. Although T-817MA has been shown
      to ameliorate amyloid-induced learning deficits in experimental AD models, it
      remains unclear whether this drug would be able to prevent oAbeta-induced
      synaptotoxicity. In the present study, we investigated the effects of T-817MA on
      the disturbances in synaptic plasticity induced by oAbeta42 and oligomeric photo
      cross-linked Abeta42 (oXLAbeta42) in a slice preparation of the CA1 subfield of
      mouse hippocampus. Both oAbeta42 and oXLAbeta42 treatments significantly reduced
      the induction of long-term potentiation (LTP). In addition, oAbeta42 treatment
      significantly facilitated long-term depression (LTD). Treatment with T-817MA
      ameliorated the LTP reduction; however, T-817MA treatment did not inhibit the
      facilitation of LTD induction by oAbeta42. These results suggest that T-817MA
      reverses oAbeta-induced LTP reduction as it may occur in the early phase of AD. 

PMID- 24112792
TI  - Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in
      aged mice.
AB  - Age-related cognitive decline is accompanied by an increase of neuronal apoptosis
      and a dysregulation of neuroplasticity-related molecules such as brain-derived
      neurotrophic factor and neurotoxic factors including beta amyloid (Abeta)
      peptide. Because it has been previously demonstrated that phosphodiesterase-5
      inhibitors (PDE5-Is) protect against hippocampal synaptic dysfunction and memory
      deficits in mouse models of Alzheimer's disease and physiological aging, we
      investigated the effect of a treatment with the PDE5-I, sildenafil, on cell
      death, pro- and antiapoptotic molecules, and Abeta production. We demonstrated
      that chronic intraperitoneal injection of sildenafil (3 mg/kg for 3 weeks)
      decreased terminal deoxyuridine triphosphate nick end labeling-positive cells in
      the CA1 hippocampal area of 26-30-month-old mice, downregulating the proapoptotic
      proteins, caspase-3 and B-cell lymphoma 2-associated X, and increasing
      antiapoptotic molecules such as B-cell lymphoma protein-2 and brain-derived
      neurotrophic factor. Also, sildenafil reverted the shifting of amyloid precursor
      protein processing toward Abeta42 production and the increase of the
      Abeta42:Abeta40 ratio in aged mice. Our data suggest that PDE5-I might be
      beneficial to treat age-related detrimental features in a physiological mouse
      model of aging.

PMID- 24112793
TI  - Interactions between GSK3beta and amyloid genes explain variance in amyloid
      burden.
AB  - The driving theoretical framework of Alzheimer's disease (AD) has been built
      around the amyloid-beta (Abeta) cascade in which amyloid pathology precedes and
      drives tau pathology. Other evidence has suggested that tau and amyloid pathology
      may arise independently. Both lines of research suggest that there may be
      epistatic relationships between genes involved in amyloid and tau
      pathophysiology. In the current study, we hypothesized that genes coding glycogen
      synthase kinase 3 (GSK-3) and comparable tau kinases would modify genetic risk
      for amyloid plaque pathology. Quantitative amyloid positron emission tomography
      data from the Alzheimer's Disease Neuroimaging Initiative served as the
      quantitative outcome in regression analyses, covarying for age, gender, and
      diagnosis. Three interactions reached statistical significance, all involving the
      GSK3beta single nucleotide polymorphism rs334543-2 with APBB2 (rs2585590,
      rs3098914) and 1 with APP (rs457581). These interactions explained 1.2%, 1.5%,
      and 1.5% of the variance in amyloid deposition respectively. Our results add to a
      growing literature on the role of GSK-3 activity in amyloid processing and
      suggest that combined variation in GSK3beta and APP-related genes may result in
      increased amyloid burden. 

PMID- 24112794
TI  - Cognitive and motor aging in female chimpanzees.
AB  - We present the first longitudinal data on cognitive and motor aging in the
      chimpanzee (Pan troglodytes). Thirty-eight adult female chimpanzees (10-54 years
      old) were studied. The apes were tested longitudinally for 3 years in a modified
      Primate Cognition Test Battery, which comprised 12 tests of physical and social
      cognition. The chimpanzees were also administered a fine motor task requiring
      them to remove a steel nut from rods of various complexity. There was little
      evidence for an age-related decline in tasks of Physical Cognition: for most
      tasks, performance was either stable or improved with repeated testing across age
      groups. An exception was Spatial Memory, for which 4 individuals more than 50
      years old experienced a significant performance decline across the 3 years of
      testing. Poorer performance with age was found in 2 tasks of Social Cognition, an
      attention-getting task and a gaze-following task. A slight motor impairment was
      also observed, with old chimpanzees improving less than younger animals with
      repeated testing on the simplest rod. Hormonal status effects were restricted to
      spatial memory, with non-cycling females outperforming cycling females
      independently of age. Unexpectedly, older chimpanzees were better than younger
      individuals in understanding causality relationships based on sound. 

PMID- 24112795
TI  - Alteration of olfactory perceptual learning and its cellular basis in aged mice.
AB  - Olfactory perceptual learning reflects an ongoing process by which animals learn
      to discriminate odorants thanks to repeated stimulations by these odorants. Adult
      neurogenesis is required for this learning to occur in young adults. The
      experiments reported here showed that olfactory perceptual learning is impaired
      with aging and that this impairment is associated with a reduction of
      neurogenesis and a decrease in granule cell responsiveness to the learned odorant
      in the olfactory bulb. Interestingly, we showed that the pharmacological
      stimulation of the noradrenergic system using dexefaroxan mimics olfactory
      perceptual learning in old mice, which is accompanied by an increase of granule
      cell responsiveness in response to the learned odorant without any improvement in
      neurogenesis. We provide the first published evidence that, in contrast to young
      adult mice, the improvement of olfactory performances in old mice is independent
      of the overall level of neurogenesis. In addition, restoring behavioral
      performances in old mice by stimulation of the noradrenergic system underlies the
      importance of this neuromodulatory system in regulating bulbar network
      plasticity. 

PMID- 24112796
TI  - Drinking context-specific associations between intimate partner violence and
      frequency and volume of alcohol consumption.
AB  - AIMS: To quantify two specific aspects of drinking in various venues (past-year
      frequency of drinking in each venue and volume consumed per venue) and assess
      their relationships with intimate partner violence. DESIGN, SETTING AND
      PARTICIPANTS: A geographic sample of married or cohabiting couples residing in 50
      medium-to-large cities in California, USA (n = 1585 couples) was obtained. Cross
      sectional survey data were collected via confidential telephone interviews.
      MEASUREMENTS: Each partner in the couple provided information about past-year
      male-to-female and female-to-male intimate partner violence (IPV), drinking
      contexts and psychosocial and demographic factors. Frequency of drinking in six
      contexts and volume consumed in those contexts were used in censored Tobit models
      to evaluate associations between IPV and male and female drinking contexts.
      FINDINGS: Risks for IPV differed among drinking contexts and were sometimes
      related to heavier volumes consumed. In fully adjusted models, male partners'
      frequency of drinking at parties at another's home {beta [standard error (SE)
      0.130 (0.060]; P = 0.030} was associated with risk for male-to-female IPV and
      frequency of drinking during quiet evenings at home was associated with risk for
      female-to-male IPV [beta (SE) 0.017 (0.008); P = 0.033]. Female partners'
      frequency of drinking with friends at home [beta (SE) -0.080 (0.037); P = 0.030]
      was associated with decreased male-to-female IPV, but volume consumed was
      associated with increased risk [beta (SE) 0.049 (0.024); P = 0.044]. CONCLUSIONS:
      The social context in which drinking occurs appears to play a role in violence
      against partners, with male violence being linked to drinking away from home and
      female violence being linked to drinking at home.

PMID- 24112797
TI  - 'It really makes good sense': the role of outcome evaluation in aphasia therapy
      in Denmark.
AB  - BACKGROUND: Measuring or evaluating outcomes is a common activity for many speech
      language therapists (SLTs). A major focus has been on external forces claiming
      outcome evaluation to optimize quality and the use of resources without
      integrating the viewpoints of SLTs. AIMS: To identify the purpose of outcome
      evaluation by letting SLTs identify not only the actual demands for outcome
      evaluation, but also the role of outcome evaluation in aphasia therapy in the
      clinic. METHODS & PROCEDURES: Twelve SLTs participated in semi-structured
      interviews to identify the demands they met for outcome evaluation as well as the
      role the outcome evaluation had in their work with people with aphasia. The
      interviews were transcribed verbatim and analysed by means of qualitative
      thematic analysis. OUTCOMES & RESULTS: Six themes corresponding with the aims of
      this study were identified. These show that the SLTs initially evaluated outcomes
      because of external demands and interests. However, they also describe the
      process as a necessary activity inherent to therapy and state that they would not
      want to be without it. The outcome evaluation is seen as an interactive process
      between SLTs, clients and possibly significant others. Not only it is seen as a
      product in which outcome and/or client satisfaction is documented, but also it is
      described as a dynamic process that benefits the clients, significant others, the
      therapy and the SLTs themselves in various ways. This role of outcome evaluation
      ranges from enhancement of insight and promotion of acceptance for the clients
      and significant others to planning the next step in therapy or in life with
      aphasia after therapy. In all of which the clients play a significant role, since
      their active participation is sought throughout the sessions. CONCLUSION &
      IMPLICATIONS: The results suggest an interesting relationship between treatment
      policy and treatment practice, where an initial administrative initiative to
      conduct outcome evaluation is adopted by the SLTs and made into a meaningful part
      of therapy in which the clients play a significant role.

PMID- 24112798
TI  - Ultrasound-guided rectus sheath block for pyloromyotomy in infants: a
      retrospective analysis of a case series.
AB  - OBJECTIVES: To analyze the applicability of US-guided rectus sheath block and to
      find out the efficacy of analgesia provided using this method without the need
      for opioids in conventional Hypertrophic pyloric stenosis (HPS) surgery in
      infants. BACKGROUND: This study describes the provision of intra- as well as
      postoperative analgesia by the use of an ultrasound-guided rectus sheath block in
      infants undergoing conventional HPS surgery under general anesthesia.
      METHODS/MATERIALS: The anesthetic protocols of 26 infants undergoing HPS surgery
      were reviewed retrospectively. RESULTS: The weight of the infants ranged from 2.6
      to 4.6 kg. The rectus sheath block was regarded as successful in all patients as
      there was no heart rate increase upon surgical skin incision in any of the
      patients. Two out of 26 (7.6%) babies needed additional intraoperative rescue
      analgesia and were administered fentanyl at 20 and 40 min after skin incision.
      Two more (a total of 4; 15.3%) babies required postoperative analgesia and were
      administered tramadol droplets and liquid ibuprofen at 15, 120 and 150 min
      postoperatively. Duration of surgery was significantly longer in those two
      patients who required intraoperative rescue analgesia (Wilcoxon-Mann-Whitney
      test: P < 0.05). These were also the only two patients who received one intra-
      and one postoperative dose of opioid each (7.6%). CONCLUSION: US-guided rectus
      sheath block seems to be a simple and quick method for the provision of intra-
      and postoperative analgesia in infants undergoing conventional HPS surgery.

PMID- 24112799
TI  - Increased expression of IL-17A and limited involvement of IL-23 in patients with
      palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised
      controlled trial.
AB  - BACKGROUND: Palmo-plantar pustular psoriasis (PPPP) and palmo-plantar pustulosis
      (PPP) are chronic skin diseases with significant impact on quality of life.
      OBJECTIVES: The purpose of this study was to study the efficacy of ustekinumab in
      PPPP and PPP and gain more knowledge on the pathophysiology and the role of the
      interleukin-23 (IL-23) signalling pathway in these diseases. METHODS: Thirty
      three patients with either PPPP (20) or PPP (13) and seven volunteers with normal
      palmo-plantar skin were recruited. Patients with PPP or PPPP were randomised (1 :
      1) to receive either an anti IL-12/IL-23 antibody (ustekinumab 45 mg) or placebo
      at day 0 and week 4 with subsequent placebo cross-over to ustekinumab at week 16.
      The primary endpoint was the proportion of patients randomized to ustekinumab
      achieving a 50% improvement in the Palmo-Plantar Pustular Area and Severity Index
      (PPPASI-50) as compared to placebo. Skin biopsies of the palms and soles of
      normal subjects and patients with PPP or PPPP were performed and analysed by RT
      PCR and immunohistochemistry. RESULTS: There was no statistically significant
      difference in the proportion of patients randomised to ustekinumab as compared to
      those randomised to placebo achieving PPPASI-50 at week 16 for patients with PPPP
      (10%, 20%; P = 1.000) or PPP (20%, 37.5%; P = 1.000) respectively. Compared to
      normal subjects an 89-fold increase in IL-17A expression was found in palms/soles
      of patients with PPPP (P = 0.006) and a 190-fold increase for patients with PPP
      (P = 0.051). There were no statistically significant changes in cytokine
      expression at week 16 in the palms and soles of patients with PPP or PPPP.
      CONCLUSION: Taken together these results suggest that ustekinumab at a dose of 45
      mg has limited efficacy in PPPP and PPP. IL-17A may have a more important role
      than IL-23 in patients with PPPP and PPP. Conclusions are limited by the small
      sample size of this study.

PMID- 24112800
TI  - Effects of family structure on risk of institutionalisation of disabled older
      people in Japan.
AB  - AIM: To examine the relationship between family structure and the risk of
      institutionalisation of disabled older people. METHODS: The participants were 286
      disabled older people aged 65 or older who were eligible to receive formal care
      services under the long-term care insurance system in a town in western Japan.
      Family structure was categorised as living alone, living only with a spouse,
      living with a son, living with a daughter and living other relatives. The risks
      of institutionalisation were estimated by logistic regression analyses. RESULTS:
      Participants living with a daughter had a significantly low odds ratio (OR) for
      institutionalisation (OR: 0.35, 95% confidence interval (CI): 0.13-0.93) and
      those living alone had a significantly high OR (OR: 2.31, 95% CI: 1.02-5.20),
      when compared to participants living with a son (regarded as the reference). The
      ORs of participants living only with a spouse and living with other relatives
      were 1.50 (95% CI: 0.59-3.79) and 0.66 (95% CI: 0.15-2.82), respectively.
      CONCLUSION: Living with a daughter could reduce the risk of institutionalisation
      for disabled older people.

PMID- 24112801
TI  - Physicochemical analysis of blood and urine in the course of acute kidney injury
      in critically ill patients: a prospective, observational study.
AB  - BACKGROUND: Sequential physicochemical alterations in blood and urine in the
      course of acute kidney injury (AKI) development have not been previously
      described. We aimed to describe these alterations in parallel to traditional
      renal and acid-base parameters. METHODS: One hundred and sixty eight consecutive
      critically ill patients with no previous kidney disease, who had an indwelling
      urinary catheter at ICU admission and who remained with the catheter for at least
      two days without dialysis were included. A sample of blood and spot urine were
      collected simultaneously, once daily, until catheter removal or dialysis
      requirement. Traditional acid-base and renal parameters were sequentially
      evaluated in parallel to blood and urinary physicochemical parameters. Patients
      were classified during this period as having or not AKI and, for patients with
      AKI, duration (transient or persistent) and severity (creatinine-based AKIN
      stage) were evaluated. RESULTS: One hundred and thirteen patients (67.3%) had
      AKI: 92 at ICU admission and 21 during the observation period. AKI development
      was characterized in blood by increased values of phosphate and unmeasured anions
      (SIG), decreased albumin, and in urine by decreased values of sodium (NaU),
      chloride (ClU) as well as high urinary strong ion difference (SIDu). These
      alterations began to occur before AKI diagnosis, and they reverted in transient
      AKI but remained in persistent AKI. NaU, ClU and albumin decreased, and
      phosphate, SIG and SIDu increased with AKI severity progression. NaU and ClU
      values increased again when AKIN stage 3 was reached. CONCLUSIONS: Simultaneous
      physicochemical analysis of blood and urine revealed standardized alterations
      that characterize AKI development in critically ill patients. These alterations
      paralleled AKI duration and severity. Future studies should consider including
      sequential evaluation of urine biochemistry as part of the armamentarium for AKI
      diagnosis and management.

PMID- 24112802
TI  - Antimicrobial activity and SAR study of new gemini imidazolium-based chlorides.
AB  - A series of 70 new 3,3'(alpha,omega-dioxaalkyl)bis(1-alkylimidazolium) chlorides
      were synthesized. They were characterized with respect to surface active
      properties and antimicrobial activity against the following pathogens:
      Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii,
      Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas
      aeruginosa, Candida krusei, and Candida albicans. In this article, besides
      description of the synthesis, we characterize a set of features of these
      compounds, concerning their structure (described by the length of the dioxaalkan
      spacer and the length of the alkyl substituent in the aromatic ring) and surface
      active properties (critical micelle concentration, value of surface tension at
      critical micelle concentration, value of surface excess, molecular area of a
      single particle, and free energy of adsorption of molecule). Then, we present a
      SAR study for Staphylococcus aureus, as one of the most widespread pathogenic
      strains, conducted with the help of the Dominance-based Rough Set Approach
      (DRSA), that involves identification of relevant features and relevant
      combinations of features being in strong relationship with a high antimicrobial
      activity of the compounds. The SAR study shows, moreover, that the antimicrobial
      activity is dependent on the type of substituents and their position at the
      chloride moiety, as well as on the surface active properties of the compounds. 

PMID- 24112803
TI  - A pH and thermosensitive choline phosphate-based delivery platform targeted to
      the acidic tumor microenvironment.
AB  - Solid tumors generally exhibit an acidic microenvironment which has been
      recognized as a potential route to distinguishing tumor from normal tissue for
      purposes of drug delivery or imaging. To this end we describe a pH and
      temperature sensitive polymeric adhesive that can be derivatized to carry drugs
      or other agents and can be tuned synthetically to bind to tumor cells at pH 6.8
      but not at pH 7.4 at 37  degrees C. The adhesive is based on the universal
      reaction between membrane phosphatidyl choline (PC) molecules and polymers
      derivatized with multiple copies of the inverse motif, choline phosphate (CP).
      The polymer family we use is a linear copolymer of a CP terminated
      tetraethoxymethacrylate and dimethylaminoethyl (DMAE) methacrylate, the latter
      providing pH sensitivity. The copolymer exhibits a lower critical solution
      temperature (LCST) just below 37  degrees C when the DMAE is uncharged at pH 7.4
      but the LCST does not occur when the group is charged at pH 6.8 due to the
      ionization hydrophilicity. At 37  degrees C the polymer binds strongly to
      mammalian cells at pH 6.8 but does not bind at pH 7.4, potentially targeting
      tumor cells existing in an acidic microenvironment. We show the binding is
      strong, reversible if the pH is raised and is followed rapidly by cellular uptake
      of the fluorescently labeled material. Drug delivery utilizing this dually
      responsive family of polymers should provide a basis for targeting tumor cells
      with minimal side reactions against untransformed counterparts. 

PMID- 24112804
TI  - The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs
      with high cell viability.
AB  - In the present study, we report on the combined efforts of material chemistry,
      engineering and biology as a systemic approach for the fabrication of high
      viability 3D printed macroporous gelatin methacrylamide constructs. First, we
      propose the use and optimization of VA-086 as a photo-initiator with enhanced
      biocompatibility compared to the conventional Irgacure 2959. Second, a parametric
      study on the printing of gelatins was performed in order to characterize and
      compare construct architectures. Hereby, the influence of the hydrogel building
      block concentration, the printing temperature, the printing pressure, the
      printing speed, and the cell density were analyzed in depth. As a result,
      scaffolds could be designed having a 100% interconnected pore network in the
      gelatin concentration range of 10-20 w/v%. In the last part, the fabrication of
      cell-laden scaffolds was studied, whereby the application for tissue engineering
      was tested by encapsulation of the hepatocarcinoma cell line (HepG2). Printing
      pressure and needle shape was revealed to impact the overall cell viability.
      Mechanically stable cell-laden gelatin methacrylamide scaffolds with high cell
      viability (>97%) could be printed. 

PMID- 24112805
TI  - A genetically-encoded KillerRed protein as an intrinsically generated
      photosensitizer for photodynamic therapy.
AB  - Photodynamic therapy (PDT) has received considerable attention as a therapeutic
      treatment for cancer and other diseases; however, it is frequently accompanied by
      prolonged phototoxic reaction of the skin due to slow clearance of synthetic
      photosensitizers (PSs) administered externally. This study was designed to
      investigate the genetic use of pKillerRed-mem, delivered using complexes of
      chitosan (CS) and poly(gamma-glutamic acid) (gammaPGA), to intracellularly
      express a membrane-targeted KillerRed protein that can be used as a potential PS
      for PDT. Following transfection with CS/pKillerRed/gammaPGA complexes, a red
      fluorescence protein of KillerRed was clearly seen at the cellular membranes.
      When exposed to green-light irradiation, the KillerRed-positive cells produced an
      excessive amount of reactive oxygen species (ROS) in a time-dependent manner.
      Data from viability assays indicate that ROS have an important role in mediating
      KillerRed-induced cytotoxicity, apoptosis, and anti-proliferation, suggesting
      that KillerRed can be used as an intrinsically generated PS for PDT treatments.
      Notably, the phototoxic reaction of KillerRed toward cells gradually became
      negligible over time, presumably because of its intracellular degradability.
      These experimental results demonstrate that this genetically encoded KillerRed is
      biodegradable and has potential for PDT-induced destruction of diseased cells. 

PMID- 24112806
TI  - Controlled release from a mechanically-stimulated thermosensitive self-heating
      composite hydrogel.
AB  - Temperature has been extensively explored as a trigger to control the delivery of
      a payload from environment-sensitive polymers. The need for an external heat
      source only allows limited spatiotemporal control over the delivery process. We
      propose a new approach by using the dissipative properties of a hydrogel matrix
      as an internal heat source when the material is mechanically loaded. The system
      is comprised of a highly dissipative hydrogel matrix and thermo-sensitive
      nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel
      to a cyclic mechanical loading for a period of 5 min leads to an increase of
      temperature of the nanoparticles. The concomitant decrease in the volume of the
      nanoparticles increases the permeability of the hydrogel network facilitating the
      release of its payload. As a proof-of-concept, we showed that the payload of the
      hydrogel is released after 5-8 min following the initiation of the mechanical
      loading. This delivery method would be particularly suited for the release of
      growth factor as it has been shown that cell receptor to growth factor is
      activated 5-20 min following a mechanical loading.

PMID- 24112807
TI  - Subjective impact of traumatic brain injury on long-term outcome at a minimum of
      10 years after trauma- first results of a survey on 368 patients from a single
      academic trauma center in Germany.
AB  - BACKGROUND: Traumatic Brain Injury (TBI) may lead to significant impairments in
      personal, social and professional life. However, knowledge of the influence on
      long-term outcome after TBI is sparse. We therefore aimed to investigate the
      subjective effects of TBI on long-term outcome at a minimum of 10 years after
      trauma in one of the largest study populations in Germany. METHODS: The current
      investigation represents a retrospective cohort study at a level I trauma center
      including physical examination or standardized questionnaires of patients with
      mild, moderate or severe isolated TBI with a minimum follow-up of 10 years. We
      investigated the subjective physical, psychological and social outcome evaluating
      the Glasgow Outcome Scale, short-form 12, and social as well as vocational living
      circumstances. RESULTS: 368 patients aged 0 to 88 years were included. Patients
      with severe TBI were younger compared to patients with moderate or mild TBI (p <
      0.05). Patients with severe TBI lived more often as single after the trauma
      impact. A significantly worse outcome was associated with higher severity of TBI
      resulting in an increased incidence of mental disability. A professional decline
      was analyzed in case of severe TBI resulting in significant loss of salary.
      CONCLUSIONS: The severity of TBI significantly influenced the subjective social
      and living conditions. Subjective mental and physical outcome as well as
      professional life depended on the severity of TBI 10 years after the injury.

PMID- 24112808
TI  - Local application of periodontal ligament stromal cells promotes soft tissue
      regeneration.
AB  - OBJECTIVES: To test the potential stimulatory effect of local application of
      periodontal ligament (PDL) stromal cells on soft tissue regeneration. MATERIALS
      AND METHODS: Fluorescently labeled PDL cells outgrown from extracted human
      premolars or phosphate-buffered saline were locally injected to the cutaneous
      wounds created on mice. Soft tissue regeneration was evaluated for 14 days using
      photographs and histomorphometry. PDL cell engraftment was tracked with confocal
      microscopy. To detect the paracrine effect of the PDL cells on soft tissue
      regeneration, PDL cell-conditioned medium (CM) was evaluated for the
      concentration of secretory factors, transforming growth factor-beta 1 (TGFbeta1).
      The effect of PDL CM on the proliferation and migration of dermal fibroblast and
      keratinocyte was tested using MTT assay and migration assay. RESULTS: The
      application of PDL cells significantly promoted soft tissue regeneration compared
      with the application of PBS. Self-replicating PDL cells were engrafted into the
      hair follicles of the host tissue. Dermal fibroblast proliferation and
      keratinocyte migration were significantly enhanced by the treatment with PDL CM.
      Physiologically significant amount of TGFbeta1 was secreted from PDL cells into
      the CM. CONCLUSION: Local injection of PDL cells promoted soft tissue
      regeneration in part by the enhancement of fibroblast proliferation and
      keratinocyte migration through a paracrine mechanism.

PMID- 24112809
TI  - Unveiling abundance and distribution of planktonic Bacteria and Archaea in a
      polynya in Amundsen Sea, Antarctica.
AB  - Polynyas, areas of open water surrounded by sea ice, are sites of intense primary
      production and ecological hotspots in the Antarctic Ocean. This study determined
      the spatial variation in communities of prokaryotes in a polynya in the Amundsen
      Sea using 454 pyrosequencing technology, and the results were compared with
      biotic and abiotic environmental factors. The bacterial abundance was correlated
      with that of phytoplankton, Phaeocystis spp. and diatoms. A cluster analysis
      indicated that the bacterial communities in the surface waters of the polynya
      were distinct from those under the sea ice. Overall, two bacterial clades,
      Polaribacter (20-64%) and uncultivated Oceanospirillaceae (7-34%), dominated the
      surface water in the polynya while the Pelagibacter clade was abundant at all
      depths (7-42%). The archaeal communities were not as diverse as the bacterial
      communities in the polynya, and marine group I was dominant (> 80%). Canonical
      correspondence analysis indicated that the oceanographic properties facilitated
      the development of distinct prokaryotic assemblages in the polynya. This analysis
      of the diversity and composition of the psychrophilic prokaryotes associated with
      high phytoplankton production provides new insights into the roles of prokaryotes
      in biogeochemical cycles in high-latitude polynyas. 

PMID- 24112810
TI  - Comparing the effects of meal replacements with an isocaloric reduced-fat diet on
      nutrient intake and lower urinary tract symptoms in obese men.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) in men are associated with
      obesity, particularly central obesity as measured by waist circumference (WC),
      and may improve with weight loss. We aimed to compare effects of a meal
      replacement based diet with isocaloric reduced-fat plan on LUTS and nutrient
      intake in obese Asian men. METHODS: Obese Asian [mean (range) body mass index of
      32.9 (30.5-42.3) kg m(-2) ] men [mean (range) age 40.2 (30-61) years] were
      randomised to a reduced-fat (< 30% of energy) diet [conventional reduced-fat diet
      (CD) group; n = 23] or meal-replacement-based plan [meal replacement (MR) group;
      n = 23], to reduce daily intake by 2000 kJ for 12 weeks. RESULTS: CD and MR
      groups had statistically significant and similar reductions in weight (-2.6 +/-
      1.9 kg versus -4.2 +/- 3.8 kg), overall LUTS severity measured with International
      Prostate Symptom Scale (IPSS) scores (-1.71 +/- 1.93 points versus -2.42 +/- 2.12
      points) and insulin resistance [homeostasis model assessment (HOMA) calculated
      from plasma glucose and insulin]. The MR group had significantly greater
      decreases in WC (-4.8 +/- 3.3 cm versus -2.5 +/- 2.3 cm), fat mass (-2.47 +/-
      3.63 kg versus -1.59 +/- 2.32 kg), fat intake, plasma C-reactive protein, and in
      storage LUTS score (-1.59 +/- 1.33 points versus -1.00 +/- 0.87 points), which
      was associated with a decreased fat intake (r = 0.48, P = 0.03). A decrease in
      overall IPSS score was associated with reductions in weight, WC and HOMA.
      CONCLUSIONS: Weight loss as a result of CD or MR had similar efficacy in
      relieving LUTS. MR produced greater reductions in fat intake, adiposity and
      storage LUTS.

PMID- 24112811
TI  - Do strigolactones contribute to plant defence?
AB  - Strigolactones are multifunctional molecules involved in several processes
      outside and within the plant. As signalling molecules in the rhizosphere, they
      favour the establishment of arbuscular mycorrhizal symbiosis, but they also act
      as host detection cues for root parasitic plants. As phytohormones, they are
      involved in the regulation of plant architecture, adventitious rooting, secondary
      growth and reproductive development, and novel roles are emerging continuously.
      In the present study, the possible involvement of strigolactones in plant defence
      responses was investigated. For this purpose, the resistance/susceptibility of
      the strigolactone-deficient tomato mutant Slccd8 against the foliar fungal
      pathogens Botrytis cinerea and Alternaria alternata was assessed. Slccd8 was more
      susceptible to both pathogens, pointing to a new role for strigolactones in plant
      defence. A reduction in the content of the defence-related hormones jasmonic
      acid, salicylic acid and abscisic acid was detected by high-performance liquid
      chromatography coupled to tandem mass spectrometry in the Slccd8 mutant,
      suggesting that hormone homeostasis is altered in the mutant. Moreover, the
      expression level of the jasmonate-dependent gene PinII, involved in the
      resistance of tomato to B. cinerea, was lower than in the corresponding wild
      type. We propose here that strigolactones play a role in the regulation of plant
      defences through their interaction with other defence-related hormones,
      especially with the jasmonic acid signalling pathway.

PMID- 24112812
TI  - Major molecular response during the first year of dasatinib, imatinib or
      nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta
      analysis.
AB  - OBJECTIVE: No randomized trials have directly compared dasatinib with nilotinib
      for the treatment of newly diagnosed chronic myeloid leukemia in the chronic
      phase. The objective of this study was to indirectly compare these therapies
      using evidence from randomized trials versus imatinib, the current standard of
      care. METHODS: Randomized trials that included either dasatinib or nilotinib as
      first-line treatment for chronic myeloid leukemia were identified in a systematic
      review. Inclusion and exclusion criteria, baseline characteristics and endpoint
      definitions were compared across trials. The outcome of interest was major
      molecular response by or at 12 months. A network meta-analysis was conducted to
      compare rates of major molecular response among therapies while adjusting for
      measurement of response by or at 12 months. RESULTS: One trial of nilotinib
      versus imatinib (ENESTnd) and two trials of dasatinib versus imatinib (DASISION
      and the S0325 Intergroup Trial) were identified. Major molecular response was
      reported by and at 12 months in ENESTnd, by 12 months in DASISION, and at 12
      months in the S0325 Intergroup Trial. In the network meta-analysis, nilotinib had
      a 97% chance of having the highest rate of major molecular response compared to
      dasatinib and imatinib, corresponding to absolute rates of major molecular
      response by month 12 of 55.2%, 44.8% and 26.7%, respectively. CONCLUSIONS: In
      this network meta-analysis, nilotinib was associated with the highest rate of
      major molecular response, compared to dasatinib and imatinib, during the first
      year of treatment in patients with newly diagnosed chronic myeloid leukemia in
      the chronic phase.

PMID- 24112813
TI  - The impact of personalized medicine on survival: comparisons of results in
      metastatic breast, colorectal and non-small-cell lung cancers.
AB  - Breast, colorectal and lung cancers represent the three most incident forms of
      cancer worldwide. Among these three "big killers", lung cancer is considered the
      one with the worst prognosis due to its high mortality even in early stages. Due
      to their more favorable prognosis, breast and colorectal cancers might appear to
      have benefited from major advances. Most oncologists who are faced with
      metastatic non-small cell lung cancer (NSCLC) find the reported results very
      frustrating when compared with those for metastatic breast (MBC) and colorectal
      cancers (MCRC). The aim of this analysis was to quantify and compare the relative
      magnitude of overall survival (OS) improvements in the first-line approaches in
      metastatic NSCLC, MBC and MCRC through the analysis of the main landmark meta
      analyses and randomized clinical trials (RCTs) of commercially available drugs.
      Five items were considered and analyzed for each cancer. Moreover we evaluated
      the real clinical impact of the results reported by each item on the entire
      population; for each "big killer" an overall hazard ratio (HR) was estimated:
      0.88 (95%(+) CI: 0.72-1.07) for MBC, 0.94 (95%(+) CI: 0.82-1.07) for MCRC, and
      about 0.80 (95%(+) CI: 0.73-0.90) for advanced NSCLC. We showed that, in the last
      decades, these three tumors had important and constant OS improvements reached
      step by step. The relative magnitude of OS improvement seems higher in metastatic
      NSCLC than MBC and MCRC. 

PMID- 24112814
TI  - The seed and soil hypothesis revisited: current state of knowledge of inherited
      genes on prognosis in breast cancer.
AB  - The crucial event in the course of malignancies such as breast cancer is its
      metastatic spread from the primary tumor of origin to distant organs. The natural
      history of a tumor is determined by the expression of its genes, and in this
      sense, knowledge has advanced dramatically in recent decades. However, much less
      is known about the role that the patient plays in the behavior of a tumor. In
      this article, we review the evidence regarding the genetic background of the host
      in metastatic tumor dissemination, providing information from epidemiological
      studies as well as from animal models and human studies. Undoubtedly, the
      elucidation of possible interpersonal variability in susceptibility to developing
      metastases would significantly contribute to improve management of cancer
      patients.

PMID- 24112815
TI  - Atrial potential in the distal great cardiac vein and the anterior
      interventricular vein as a guide for mapping and ablation of focal atrial
      tachycardia originating from the left atrial appendage.

PMID- 24112816
TI  - Tissue factor purified from different cellular sources and non-glycosylated
      tissue factor show similar procoagulant activity.

PMID- 24112818
TI  - When abstracts conflict with published papers.

PMID- 24112817
TI  - Effect of transcranial direct current stimulation combined with gait and mobility
      training on functionality in children with cerebral palsy: study protocol for a
      double-blind randomized controlled clinical trial.
AB  - BACKGROUND: The project proposes three innovative intervention techniques
      (treadmill training, mobility training with virtual reality and transcranial
      direct current stimulation that can be safely administered to children with
      cerebral palsy. The combination of transcranial stimulation and physical therapy
      resources will provide the training of a specific task with multiple rhythmic
      repetitions of the phases of the gait cycle, providing rich sensory stimuli with
      a modified excitability threshold of the primary motor cortex to enhance local
      synaptic efficacy and potentiate motor learning. METHODS/DESIGN: A prospective,
      double-blind, randomized, controlled, analytical, clinical trial will be carried
      out.Eligible participants will be children with cerebral palsy classified on
      levels I, II and III of the Gross Motor Function Classification System between
      four and ten years of age. The participants will be randomly allocated to four
      groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2)
      gait training on a treadmill with active transcranial stimulation; 3) mobility
      training with virtual reality and placebo transcranial stimulation; 4) mobility
      training with virtual reality and active transcranial stimulation. Transcranial
      direct current stimulation will be applied with the anodal electrode positioned
      in the region of the dominant hemisphere over C3, corresponding to the primary
      motor cortex, and the cathode positioned in the supraorbital region contralateral
      to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training
      and mobility training with virtual reality will be performed in 30-minute
      sessions five times a week for two weeks (total of 10 sessions). Evaluations will
      be performed on four occasions: one week prior to the intervention; one week
      following the intervention; one month after the end of the intervention;and 3
      months after the end of the intervention. The evaluations will involve three
      dimensional gait analysis, analysis of cortex excitability (motor threshold and
      motor evoked potential), Six-Minute Walk Test, Timed Up-and-Go Test, Pediatric
      Evaluation Disability Inventory, Gross Motor Function Measure, Berg Balance
      Scale, stabilometry, maximum respiratory pressure and an effort test. DISCUSSION:
      This paper offers a detailed description of a prospective, double-blind,
      randomized, controlled, analytical, clinical trial aimed at demonstrating the
      effect combining transcranial stimulation with treadmill and mobility training on
      functionality and primary cortex excitability in children with Cerebral Palsy
      classified on Gross Motor Function Classification System levels I, II and III.
      The results will be published and will contribute to evidence regarding the use
      of treadmill training on this population. TRIAL REGISTRATION: ReBEC RBR-9B5DH7.

PMID- 24112819
TI  - Emissions generated by sugarcane burning promote genotoxicity in rural workers: a
      case study in Barretos, Brazil.
AB  - BACKGROUND: To determine the possible genotoxic effect of exposure to the smoke
      generated by biomass burning on workers involved in manual sugar cane harvesting.
      METHODS: The frequency of micronuclei in exfoliated buccal cells and peripheral
      blood lymphocytes was determined in sugarcane workers in the Barretos region of
      Brazil, during the harvest season and compared to a control population, comprised
      of administrative employees of Barretos Cancer Hospital. RESULTS: The frequency
      of micronuclei was higher in the sugar cane workers. The mean frequency in blood
      lymphocytes (micronuclei/1000 cells) in the test group was 8.22 versus 1.27 in
      the control group. The same effect was observed when exfoliated buccal cells were
      considered (22.75 and 9.70 micronuclei/1000 cells for sugar cane workers and
      controls, respectively). CONCLUSION: Exposure to emissions produced by the
      burning of sugar cane during harvesting induces genomic instability in workers,
      indicating the necessity of adopting more advanced techniques of harvesting sugar
      cane to preserve human health.

PMID- 24112820
TI  - Feeding tubes and health costs postinsertion in nursing home residents with
      advanced dementia.
AB  - CONTEXT: The best evidence suggests that feeding tubes are ineffective in persons
      with advanced dementia. Little is known about their health care costs.
      OBJECTIVES: To estimate Medicare costs attributable to inpatient care among
      nursing home (NH) residents with advanced dementia during the year following the
      placement of a percutaneous endoscopic gastrostomy (PEG) tube during an index
      hospitalization. METHODS: Medicare claims (1999-2009) and Minimum Data Set data
      (1999-2009) were used to estimate Medicare costs attributable to inpatient care
      among NH residents with advanced dementia during the year following the placement
      of a PEG tube and compared with those who did not get a PEG tube. The study used
      a 3:1 propensity-matched cohort design. RESULTS: Matched residents with (n=1924,
      68.9% female, 28.8% African American, average age 83.1 years) and without
      (weighted n=1924, unique n=4337) PEG insertion showed comparable sociodemographic
      characteristics, similar rates of feeding tube risk factors, and similar
      mortality (51.9% 180 day mortality among those with a feeding tube vs. 49.8%
      among those without a feeding tube, P=0.11). One year hospital costs were $2224
      higher in NH residents with a feeding tube ($10,191 vs. $7967, 95% CI of
      difference=$1514, $2933), with those with a feeding tube likely to spend more
      time in an intensive care unit (1.92 vs. 1.29 days, 95% CI of difference=0.34,
      0.92 days). CONCLUSION: In an analysis controlling for selection bias, PEG tube
      insertion is associated with a small but significant increase in annual inpatient
      health care costs, as well as in hospital and intensive care unit days,
      postinsertion.

PMID- 24112822
TI  - The relationship between cannabis outcome expectancies and cannabis refusal self
      efficacy in a treatment population.
AB  - BACKGROUND AND AIMS: Self-efficacy beliefs and outcome expectancies are central
      to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and
      clinical utility of applying both SCT constructs. This study examined the
      relationship between refusal self-efficacy and outcome expectancies in a sample
      of cannabis users, and tested formal mediational models. DESIGN: Patients
      referred for cannabis treatment completed a comprehensive clinical assessment,
      including recently validated cannabis expectancy and refusal self-efficacy
      scales. SETTING: A hospital alcohol and drug out-patient clinic. PARTICIPANTS:
      Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard
      deviation (SD) 9.39]. MEASUREMENTS: The Cannabis Expectancy Questionnaire (CEQ)
      and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along
      with measures of cannabis severity [Severity of Dependence Scale (SDS)] and
      cannabis consumption. FINDINGS: Positive (beta = -0.29, P < 0.001) and negative
      (beta = -0.19, P < 0.001) cannabis outcome expectancies were associated
      significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully
      mediated the association between negative expectancy and weekly consumption [95%
      confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of
      positive expectancy on weekly consumption (95% CI = 0.06, 0.17). CONCLUSIONS:
      Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief
      that he or she can abstain from cannabis use) mediates part of the association
      between cannabis outcome expectancies (perceived consequences of cannabis use)
      and cannabis use.

PMID- 24112821
TI  - The index 'Treatment Duration Control' for enabling randomized controlled trials
      with variation in duration of treatment of chronic pain patients.
AB  - BACKGROUND: Treatment duration varies with the type of therapy and a patient's
      recovery speed. Including such a variation in randomized controlled trials (RCTs)
      enables comparison of the actual therapeutic potential of different therapies in
      clinical care. An index, Treatment Duration Control (TDC) of outcome scores was
      developed to help decide when to end treatment and also to determine treatment
      outcome by a blinded assessor. In contrast to traditional Routine Outcome
      Monitoring which considers raw score changes, TDC uses relative change. METHODS:
      Our theory shows that if a patient with the largest baseline scores in a sample
      requires a relative decrease by treatment factor T to reach a zone of low score
      values (functional status), any patient with smaller baselines will attain
      functional status with T. Furthermore, the end score values are proportional to
      the baseline. These characteristics concur with findings from the literature that
      a patient's assessment of 'much improved' following treatment (related to
      attaining functional status) is associated with a particular relative decrease in
      pain intensity yielding a final pain intensity that is proportional to the
      baseline. Regarding the TDC-procedure: those patient's scores that were related
      to pronounced signs and symptoms, were selected for adaptive testing (reference
      scores). A Contrast-value was determined for each reference score between its
      reference level and a subsequent level, and averaging all Contrast-values yielded
      TDC. A cut-off point related to factor T for attaining functional status, was the
      TDC-criterion to end a patient's treatment as being successful. The use of TDC
      has been illustrated in RCT data from 118 chronic pain patients with myogenous
      Temporomandibular Disorders, and the TDC-criterion was validated. RESULTS: The
      TDC-criterion of successful/unsuccessful treatment approximated the cut-off
      separating two patient subgroups in a bimodal post-treatment distribution of TDC
      values. Pain intensity decreased to residual levels and Health-Related Quality of
      Life (HRQoL) increased to normal levels, following successful treatment according
      to TDC. The post-treatment TDC-values were independent from the baseline values
      of pain intensity or HRQoL, and thus independent from the patient's baseline
      severity of myogenous Temporomandibular Disorders. CONCLUSIONS: TDC enables RCTs
      that have a variable therapy- and patient-specific duration.

PMID- 24112823
TI  - The isolation and characterization of a telomerase immortalized goat trophoblast
      cell line.
AB  - Trophoblast cells play vital roles in the processes of embryonic implantation and
      placentation. Many toxicological compounds can induce the malfunction of
      trophoblast cells, resulting in implantation failure or early embryonic loss. The
      finite lifespan of primary trophoblast cells limits investigation of the long
      term effects of some toxicological compounds on trophoblast cells in vitro. In
      this study, primary goat trophoblast cells were purified by density gradient
      centrifugation and specific immuno-affinity purification. Then, the purified
      cells were immortalized through transfection of a plasmid containing the human
      telomerase reverse transcriptase (hTERT) gene. hTERT-transfected goat trophoblast
      cells (hTERT-GTCs) could steadily express hTERT gene and exhibit higher
      telomerase activity, and persistently proliferate without any signs of senescence
      up to 50 passages. The immortalized goat trophoblast cells still possessed the
      basic and key properties of normal primary goat trophoblast cells to express the
      specific intracellular marker cytokeratin 7 (CK-7) and secrete chorionic
      gonadotrophin beta-subunit (CG-beta) and placental lactogen (PL). Further studies
      showed that the immortalized goat trophoblast cells expressed vimentin and non
      classical MHC class I antigen and exhibited invasive phenotype, suggesting that
      the immortalized goat trophoblasts resembled human extravillous trophoblasts. In
      addition, this cell line did not show neoplastic transformation either in vivo or
      in vitro. We concluded the immortalized goat trophoblast cells by hTERT
      transfection retained the basic and key characteristics of primary trophoblast
      cells and may provide a useful model to study the effects of some toxicological
      compounds on trophoblast cells. 

PMID- 24112824
TI  - Geometry of the randomized evidence for treatments of pulmonary hypertension.
AB  - OBJECTIVE: We studied the entire agenda of randomized clinical trials in
      pulmonary hypertension (PH) using sociological methods. We explored the geometry
      of the PH network to interpret the evidence on multiple competing treatments for
      the same indication. DESIGN: We searched MEDLINE, Embase and Cochrane Library
      Databases for published studies. We queried clinicaltrials.gov and WHO
      International Clinical Trials Registry platform for non-published studies.
      RESULTS: We found 75 randomized trials (41 published [n = 4136 participants] and
      34 registered unpublished [planned n = 3470 participants]). Of the published
      randomized studies, all used placebo as the comparator arm except for two
      nonindustry-sponsored comparisons between phosphodiestearase-5 (PDE-5) inhibitors
      and endothelin receptor antagonists (ERA), and one study comparing two different
      regimens of treprostinil. Similarly, only five unpublished/ongoing trials used an
      active PH treatment as comparator (PDE-5 inhibitors versus ERA (n = 3), different
      doses of sildenafil (n = 1) and two formulations of epoprostenol (n = 1). Of the
      75 trials, 47 were sponsored by the manufacturer of the tested active product(s),
      and only two trials were sponsored by two companies comparing their products.
      CONCLUSIONS: The relative merits of different treatment options are not directly
      known, as there are very few head-to-head comparisons. A limited number of
      ongoing studies are using active FDA-approved PH-treatments for comparison. This
      lack of information can be overcome by carefully designing comparative
      effectiveness trials.

PMID- 24112825
TI  - Grip strength measurement in older adults in Taiwan: a comparison of three
      testing positions.
AB  - AIM: The purpose of this study was to explore the effects of three commonly used
      positions on grip strength measurement in older people. METHOD: A total of 249
      (113 women, 136 men) older participants, 72.8 +/- 6.5 years old, participated in
      this study. Grip strength (kg) was measured in three positions: (i) the standard
      posture (sitting, elbow flexed 90 degrees ) suggested by the American Society of
      Hand Therapists; (ii) standing, elbow flexed 90 degrees ; and (3) standing, elbow
      fully extended. RESULTS: One-way repeated measures analysis of variance showed
      that grip strength was significantly greater in the standing position with the
      elbow fully extended than in the other two positions. CONCLUSIONS: The grip
      strengths obtained from the three positions were not all comparable in our
      community-dwelling older adults. Clinicians and researchers need to be cautious
      when choosing testing position for assessing and interpreting grip strength
      results obtained from these positions.

PMID- 24112826
TI  - Matrix solid phase dispersion assisted enzymatic hydrolysis as a novel approach
      for cocaine and opiates isolation from human hair.
AB  - The possibility of assisting enzymatic hydrolysis (EH) procedures by sample
      disruption mechanisms inherent to matrix solid phase dispersion (MSPD) has been
      explored in the current study. EH of hair specimens from poly-drug abusers was
      assisted by dispersing/blending the sample (0.05 g) with alumina (2.25 g) before
      loading the dissolved enzyme (6 mL of 1 mg mL(-1) Pronase E in 1.4 M/1.4 M
      Tris/HCl, pH 7.3) through the hair-alumina solid phase packaged inside a
      disposable MSPD syringe. The MSPD-EH method was developed, and it proved to offer
      quantitative results when isolating cocaine, benzoylecgonine (BZE), codeine,
      morphine and 6-monoacethylmorphine (6-MAM) from human hair samples. The procedure
      allows an on column clean-up/pre-concentration procedure of the isolated targets
      by attaching a previously conditioned Oasis HLB cartridge to the end of the MSPD
      syringe. The EH procedure of human hair with Pronase E can therefore be shortened
      to approximately 30 min. Within this time, sample blending/dispersion, MSPD
      syringe package, elution (EH when dissolved Pronase E is passing through the
      sample-dispersant bed), and extract clean-up and target pre-concentration stages
      are achieved. Gas chromatography-mass spectrometry (GC-MS) was used for
      determining each target after elution from the Oasis HLB cartridges with 2 mL of
      2% (v/v) acetic acid in methanol, concentration by N2 stream evaporation, and
      dried extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide
      (BSTFA) and chlorotrimethylsilane (TMCS). The method was validated according to
      the guidance for bioanalytical method validation of the US Department of Health
      and Human Services, Food and Drug Administration. The simplicity of the proposed
      approach makes it a useful procedure for screening/quantifying drugs of abuse in
      hair specimens from poly-drug abusers.

PMID- 24112827
TI  - Acute molecular responses in untrained and trained muscle subjected to aerobic
      and resistance exercise training versus resistance training alone.
AB  - AIM: This study assessed and compared acute muscle molecular responses before and
      after 5-week training, employing either aerobic (AE) and resistance exercise (RE)
      or RE only. METHODS: Ten men performed one-legged RE, while the contralateral
      limb performed AE followed by RE 6 h later (AE+RE). Before (untrained) and after
      (trained) the intervention, acute bouts of RE were performed with or without
      preceding AE. Biopsies were obtained from m. vastus lateralis of each leg pre-
      and 3 h post-RE to determine mRNA levels of VEGF, PGC-1alpha, MuRF-1, atrogin-1,
      myostatin and phosphorylation of mTOR, p70S6K, rpS6 and eEF2. RESULTS: PGC-1alpha
      and VEGF expression increased (P < 0.05) after acute RE in the untrained, but not
      the trained state. These markers showed greater response after AE+RE than RE in
      either condition. Myostatin was lower after AE+RE than RE, both before and after
      training. AE+RE showed higher MuRF-1 and atrogin-1 expression than RE in the
      untrained, not the trained state. Exercise increased (P < 0.05) p70S6K
      phosphorylation both before and after training, yet this increase tended to be
      more prominent for AE+RE than RE before training. Phosphorylation of p70S6K was
      greater in trained muscle. Changes in these markers did not correlate with
      exercise-induced alterations in strength or muscle size. CONCLUSION: Concurrent
      exercise in untrained skeletal muscle prompts global molecular responses
      consistent with resulting whole muscle adaptations. Yet, training blunts the more
      robust anabolic response shown after AE+RE compared with RE. This study
      challenges the concept that single molecular markers could predict training
      induced changes in muscle size or strength.

PMID- 24112828
TI  - [Limitation of therapeutic effort: Approach to a combined view].
AB  - Over the past few decades, we have been witnessing that increasing fewer people
      pass away at home and increasing more do so within the hospital. More
      specifically, 20% of deaths now occur in an intensive care unit (ICU). However,
      death in the ICU has become a highly technical process. This sometimes originates
      excesses because the resources used are not proportionate related to the purposes
      pursued (futility). It may create situations that do not respect the person's
      dignity throughout the death process. It is within this context that the
      situation of the clinical procedure called "limitation of the therapeutic effort"
      (LTE) is reviewed. This has become a true bridge between Intensive Care and
      Palliative Care. Its final goal is to guarantee a dignified and painless death
      for the terminally ill.

PMID- 24112829
TI  - Epicutaneous application of house dust mite induces thymic stromal lymphopoietin
      in nonlesional skin of patients with atopic dermatitis.

PMID- 24112830
TI  - Bacterial pathogens, virulence mechanism and host defence in marine macroalgae.
AB  - Macroalgae are important ecosystem engineers in temperate marine waters. The
      function of macroalgae is intimately linked to the composition and structure of
      their epibiotic bacterial, communities, and evidence has emerged that bacteria
      can also have a negative impact on their host by causing disease. A few examples
      exist where bacteria have been unambiguously linked to macroalgal disease,
      however in many cases, pathogenicity has not been clearly separated from
      saprophytic behaviour or secondary colonization after disease initiation.
      Nevertheless, pathogenic pressure by bacteria might be substantial, as macroalgae
      have evolved a range of innate and induced defence mechanism that have the
      potential to control bacterial attacks. The presence and abundance of virulence
      factors in marine bacteria, which have not previously been recognized as
      pathogens, also represents an underappreciated, opportunistic potential for
      disease. Given that virulence expression in opportunistic pathogens is often
      dependent on environmental conditions, we predict that current and future
      anthropogenic changes in the marine environment will lead to an increase in the
      occurrence of macroalgal disease. This review highlights important areas of
      research that require future attention to understand the link between
      environmental change, opportunistic pathogens and macroalgal health in the
      world's oceans. 

PMID- 24112831
TI  - A fatal case of acquired hemophagocytic lymphohistiocytosis (macrophage
      activation syndrome) in the initial course of dermatomyositis with anti-Jo-1
      antibody.

PMID- 24112832
TI  - Chemical inhibition of acetyl coenzyme A carboxylase as a strategy to increase
      polyhydroxybutyrate yields in transgenic sugarcane.
AB  - Polyhydroxybutyrate (PHB) is a naturally occurring bacterial polymer that can be
      used as a biodegradable replacement for some petrochemical-derived plastics.
      Polyhydroxybutyrate is produced commercially by fermentation, but to reduce
      production costs, efforts are underway to produce it in engineered plants,
      including sugarcane. However, PHB levels in this high-biomass crop are not yet
      commercially viable. Chemical ripening with herbicides is a strategy used to
      enhance sucrose production in sugarcane and was investigated here as a tool to
      increase PHB production. Class A herbicides inhibit ACCase activity and thus
      reduce fatty acid biosynthesis, with which PHB production competes directly for
      substrate. Treatment of PHB-producing transgenic sugarcane plants with 100 MUM of
      the class A herbicide fluazifop resulted in a fourfold increase in PHB content in
      the leaves, which peaked ten days post-treatment. The minimum effective
      concentration of herbicide required to maximize PHB production was 30 MUM for
      fluazifop and 70 MUM for butroxydim when applied to saturation. Application of a
      range of class A herbicides from the DIM and FOP groups consistently resulted in
      increased PHB yields, particularly in immature leaf tissue. Butroxydim or
      fluazifop treatment of mature transgenic sugarcane grown under glasshouse
      conditions increased the total leaf biomass yield of PHB by 50%-60%. Application
      of an ACCase inhibitor in the form of a class A herbicide to mature sugarcane
      plants prior to harvest is a promising strategy for improving overall PHB yield.
      Further testing is required on field-grown transgenic sugarcane to more precisely
      determine the effectiveness of this strategy.

PMID- 24112833
TI  - Anionic surfactant enhanced phosphate desorption from Mg/Al-layered double
      hydroxides by micelle formation.
AB  - Desorption of interlayer hydrogen phosphate (HPO4) from hydrogen phosphate
      intercalated Mg/Al-layered double hydroxide (LDH-HPO4) by anion exchange with
      surfactant anions has been investigated under controlled conditions. Three types
      of surfactant, Dodecylbenzenesulphonate (DBS), Dodecylsulphate (DS) and 1
      Octanesulphonate (OS), anions were used for intercalation experiments over a
      range of concentrations, and for all solutions, it was shown that the desorption
      of hydrogen phosphate is enhanced at concentrations close to the critical micelle
      concentration (CMC). Intercalation of the surfactant anions into LDH-HPO4 was
      confirmed by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT
      IR) and Scanning electron microscopy (SEM). More than 90% removal of the hydrogen
      phosphate was achieved at CMC. Repeat adsorption tests to investigate
      recyclability showed that desorption with 0.005 M DBS improved subsequent
      phosphate re-adsorption, allowing around 90% of the original adsorption over
      three cycles. This is much higher than when desorption was conducted using either
      Na2CO3 or NaCl-NaOH solutions, even at much higher concentrations. This study
      suggests potential economic and environmental advantages in using these
      surfactants in improving the cycling performance of LDH materials as absorbents
      for clean-up of water systems.

PMID- 24112834
TI  - Forces of interactions between iron and aluminum silicates: effect of water
      chemistry and polymer coatings.
AB  - Atomic force microscopy-based force spectroscopy (AFM) was employed to
      investigate the forces of interaction between aluminum silicates (mica and a
      synthetic aluminum-silicate) and iron particles, both bare and coated with
      carboxymethyl cellulose (CMC) polymer. Experiments were conducted in water and
      salt solutions (100mM NaCl and 100mM CaCl2) at pH 5.5, in water at pH 4 and 8,
      and in 10mg/l humic acid solutions. In addition, humic acid sorption onto the
      synthetic aluminum-silicate was probed with a quartz crystal microbalance with
      dissipation monitoring (QCM-D). Interactions between bare iron particles and
      aluminum silicate were attractive except at pH 8 and in the presence of humic
      acids in which case forces upon approach were repulsive. Interactions between
      bare iron and mica were similar, except that repulsive forces upon approach were
      measured in 100mM NaCl solutions, possibly due to increased hydration of mica
      compared to aluminum silicate. Interactions between CMC coated iron particles and
      aluminum-silicates were either repulsive or at most weakly attractive, likely due
      to repulsive electro-steric forces associated with the CMC. QCM-D results
      indicated that humic acids adsorbed to aluminum silicate, producing electro
      steric repulsion to coated and uncoated iron. AFM data were successfully modeled
      using extended DLVO theory and a modified Ohshima's model. This modeling provided
      insights into the contributions of various processes to the measured interaction
      forces, highlighting the importance of van der Waals and hydration forces. 

PMID- 24112835
TI  - Low-frequency dielectric properties of three bentonites at different adsorbed
      water states.
AB  - Three bentonites of varying smectite content were investigated by dielectric
      spectroscopy in the frequency range 10(-4) to 10(6) Hz after storage at well
      defined humidities. The identification of relaxation processes from complex
      permittivity measurements was difficult, since conductivity effects were
      superimposed on the underlying relaxations. Relaxation peaks revealed by the
      dissipation factor indicated the occurrence of interfacial processes between
      10(2) and 10(6) Hz. The intensity of the polarization of the electrochemical
      double-layer at the clay-water interface was promoted by increasing water content
      and was shifted to higher frequencies the higher the water content in the
      bentonites. Below ~1 Hz, electrode polarization (EP) was shown to be a
      participating process with capacitance values ranging from 0.6*10(-3) to 7.3*10(
      3)F due to the accumulated charges. An equivalent circuit model was introduced
      that successfully described the low-frequency dielectric behavior of bentonites
      at low moisture levels. An included series R-CPE connection was used to describe
      the double-layer relaxation. At water contents up to 17%, the bulk resistivity
      was mainly influenced by smectite content and cation exchange capacity, whereas
      at water contents of >=19%, interlayer occupation and hydration state became more
      important.

PMID- 24112836
TI  - Statistical optimization, interaction analysis and desorption studies for the azo
      dyes adsorption onto chitosan films.
AB  - Chitosan films (CF) were applied to remove azo dyes (tartrazine and amaranth)
      from aqueous solutions by adsorption. CF were prepared by casting technique and
      characterized. Response surface methodology was employed to optimize the
      adsorption process as a function of pH (2, 3 and 4) and CF concentration (100,
      150 and 200 mg L(-1)). The possible interactions CF-dyes were investigated by
      Fourier transform infrared spectroscopy, dispersive energy X-ray spectroscopy,
      thermogravimetric analysis and color parameters. Adsorption-desorption cycles
      were also performed. The more appropriate conditions for the adsorption of both
      dyes were pH of 2 and CF concentration of 100 mg L(-1). Under these conditions,
      the tartrazine and amaranth adsorption capacities were 413.8 and 278.3 mg g(-1),
      respectively. The interactions between the CF protonated amino groups and anionic
      form of the dyes at pH 2 were confirmed. Desorption experiments showed that the
      CF can keep its adsorption capacity maximum for two cycles.

PMID- 24112837
TI  - Macroporous polypyrrole-TiO2 composites with improved photoactivity and
      electrochemical sensitivity.
AB  - Macroporous polypyrrole (PPy)-TiO2 composites were prepared by in situ oxidative
      polymerization of pyrrole in the macropores of TiO2. The formation mechanism of
      the PPy nanoparticles, including nucleation and further growth, was proposed by
      studying the particle growth process with increasing reaction time. The special
      growth process favors the formation of good cohesion and stabilized interface
      between the inorganic and organic phases. The conversion ratio of pyrrole monomer
      is in the range of 65.3-97.5%, and PPy content in the composites can reach as
      high as 21.04% with well preservation of the macroporous framework. Furthermore,
      dispersed PPy particles of ~100 nm in size can be obtained by etching the
      composites in HF acid, which is smaller than the PPy particles synthesized in the
      absence of the TiO2 template due to the pore-confinement effect. The composites
      show improved photoactivity on degradation of dye under simulated sunlight
      irradiation and electrocatalytic activity toward the detection of H2O2 in 0.1M
      phosphate buffer solution. Synergetic interaction between the two components and
      the porous structure is considered to be responsible for the enhanced properties
      of the new composites.

PMID- 24112838
TI  - Fabrication of monodisperse anisotropic silica hollow microspheres using
      polymeric cave particles as templates.
AB  - Monodisperse anisotropic poly(styrene-co-divinylbenzene) (PS-DVB) particles with
      single cavity structures were synthesized using a modified dispersion
      polymerization method. The effects of DVB adding modes and speeds on the particle
      morphologies were studied. Using the PS-DVB cave particles as templates,
      monodisperse anisotropic silica (SiO2) hollow microspheres were fabricated
      facilely. The obtained anisotropic silica hollow spheres had a potential
      application in rapid waste removal and detoxification extraction with a very
      simple procedure. 

PMID- 24112839
TI  - Micellization of true amphoteric surfactants.
AB  - The physical chemical behavior of a series of N-alkyl amino acid-based
      surfactants has been investigated. The series comprises four different types of
      amino acids as polar headgroups: glycine, aminomalonic acid, aspartic acid and
      glutamic acid, and for each type three homologues were synthesized: the octyl,
      decyl and dodecyl derivative. Aminomalonic acid, aspartic acid and glutamic acid
      are dicarboxylic amino acids with one, two and three methylene groups as spacer
      between the carboxylic groups, respectively. Compared with the more common N-acyl
      surfactants based on the same amino acids, many of the N-alkyl derivatives
      exhibited relatively high Krafft temperatures. The N-alkyl derivatives also had
      considerably lower critical micelle concentrations (CMCs) and they gave low
      values of surface tension at the CMC. The length of the spacer between the two
      carboxylic groups did not much influence the micellization. Some of the
      surfactants, in particular the lower homologues of N-alkylglycinate surfactants,
      gave unusually low surface tension values. The low values are most likely due to
      formation of a mixed monolayer at the surface, comprising of alternating anionic
      N-alkylglycinate and cationic N-protonated-N-alkylglycine. In a plot of
      conductivity vs. surfactant concentration there was no kink on the curve around
      the CMC, as determined by tensiometry. The absence of such a kink is in
      accordance with the view that self-assembly of the N-alkyl amino acid-based
      surfactants involves formation of mixed micelles consisting of alternating N
      alkyl amino acid anion and N-protonated-N-alkyl amino acid also in the bulk
      solution. The protonation of the N-alkyl amino acid anion, which generates
      hydroxyl ions, is driven by the energetically favorable formation of mixed
      micelles consisting of anionic and cationic amphiphiles. 

PMID- 24112840
TI  - Influence of particle size and tunable interactions on isotropic-nematic
      transition of block copolymer single crystal platelet suspensions.
AB  - We have studied the influence of the particle size and the tunable lateral
      interactions on the isotropic-nematic (I-N) phase transition of a plate-like
      colloidal system. The particles are single crystals of a block copolymer PS-b
      PLLA (BCSC) prepared using a self-seeding procedure. These lozenge shape crystals
      have a uniform thickness and a narrowly distributed lateral size. The equilibrium
      phase behavior and I-N phase transition have been characterized using crossed
      polarizers at the room temperature. A nematic phase exists for all systems with
      size ranging from 700 to 4000 nm. For smaller crystals (<1200 nm), the I-N phase
      transition follows a process of slow sedimentation and subsequent macroscopic
      phase separation, resulting in a highly oriented nematic phase with a sharp I-N
      interface. For larger crystals (>=1200 nm), the I-N phase transition follows a
      process of nucleation and subsequent sedimentation, resulting in a random
      orientation of crystals in the nematic phase and a rough I-N interface. The I-N
      transition occurs at a very low volume fraction (<0.2%) for all systems, which is
      at least one order of magnitude lower than the theoretical prediction (2-7%).
      However, addition of a small amount of ethanol into the solution, the I-N
      transition can be significantly suppressed. These results demonstrate the
      existence of a lateral attraction between crystals, which is due to the polar
      attraction between the uncovered PLLA crystalline domains. Polar ethanol
      molecules can adsorb to the PLLA crystalline surface and screen the attraction.
      The attraction exhibits highly orientation-dependent. To further demonstrate this
      highly directional attraction, we have prepared two composite single crystal
      suspensions with PLLA homopolymer, which have a much wider open angle for the
      polar attraction. Indeed, the resulting liquid crystalline phases show much less
      horizontal ordering.

PMID- 24112841
TI  - Room temperature thermotropic liquid crystalline phases of catanionic surfactants
      derived from quaternary ammonium surfactants and bis(2-ethylhexyl)sulfosuccinate.
AB  - HYPOTHESIS: Properties of catanionic surfactants can be tailored by the choice of
      appropriate headgroups and hydrocarbon tails. Thermal behavior of catanionic
      surfactants can be influenced by the length and number of alkyl chains.
      EXPERIMENTS: A series of eight catanionic surfactants were synthesized from
      quaternary ammonium surfactants as the cationic counterpart and bis(2
      ethylhexyl)sulfosuccinate (AOT) as the anionic counterpart. The thermal
      properties and the liquid crystalline properties of these catanionic surfactants
      were studied by the following methods: Thermal Gravimetric Analysis (TGA),
      Differential Scanning Calorimetry (DSC), Hot-Stage Polarized Light Microscopy
      (HSPLM), and X-ray Diffraction (XRD). FINDINGS: The results indicate that
      transition temperatures, enthalpies of transition, and mesophase structures vary
      with the length and number of chains attached to the quaternary nitrogen. These
      compounds exhibit room temperature liquid crystalline (LC) textures that are
      predominantly "fan-like," as observed by HSPLM, and phases that are hexagonal
      columnar, as observed by XRD, with the exception of one compound which exists as
      a nematic liquid crystal at 25 degrees C. Additionally, all of the surfactants
      also exhibit thermal stability in the range of 256-300 degrees C.

PMID- 24112842
TI  - Green synthesis and photo-catalytic performances for ZnO-reduced graphene oxide
      nanocomposites.
AB  - The zinc oxide (ZnO)-reduced graphene oxide (RGO) nanocomposites were greenly
      synthesized by one-step hydrothermal reaction with ZnCl2 and graphite oxide (GO)
      as precursors without extra reductant. The photo-catalytic performances
      consisting of the photo-degradation of Rhodamine B (RhB) and the photo-reduction
      of CO2 under the illumination of simulated solar light at ambient temperature
      were investigated. It was validated that the ZnO spherical particles assembled by
      ZnO nanorods with an average diameter of 150nm are uniformly deposited on the RGO
      sheets. Meanwhile, due to the introduction of RGO, the light adsorption scope of
      ZnO is enlarged, the size of ZnO is decreased, the degree of crystallinity is
      improved and the self-aggregation of the ZnO particles is effectively prevented.
      Comparing with the pure ZnO particles, the efficiency of the nanocomposites for
      the photo-degradation of RhB is increased by 39% and the yield of methanol from
      the reduction of CO2 is improved by 75%. The mechanisms that may explain the
      enhanced properties of as-synthesized ZnO-RGO for both the photo-degradation of
      RhB and the reduction of CO2 were also proposed. 

PMID- 24112843
TI  - Hybrid cellulase aggregate with a silica core for hydrolysis of cellulose and
      biomass.
AB  - Cellulase is an important enzyme for hydrolyzing cellulose to form glucose. To
      recycle cellulase after the reaction, cellulase is often immobilized on solid
      supports but its activity is also compromised. In this study, we show a new
      hybrid cellulase aggregate with a silica core, which is prepared by physical
      adsorption of cross-linked cellulase on a highly porous solid support silica gel.
      The hybrid cellulase aggregate exhibits highest activity at pH 4.8 and 51 degrees
      C, similar to the optimum condition of free cellulase. This hybrid cellulase
      aggregate can produce 3.4 g/L of glucose within 2 h, which is two times higher
      than glucose produced by using cross-linked cellulase aggregate alone (without
      silica core). Another advantage of the hybrid cellulase aggregate is that it can
      settle down naturally after the hydrolysis of cellulose, thanks to the presence
      of the silica core. To show its practical applications, we also study the
      hydrolysis of palm oil fiber by using the hybrid cellulase aggregate. Up to 5.0
      g/L of glucose can be produced within 24h, and this process can be repeated five
      times with only 19% decrease in activity.

PMID- 24112844
TI  - Formation mechanism of highly luminescent silica capsules incorporating multiple
      hydrophobic quantum dots with various emission wavelengths.
AB  - A synthesis process was reconsidered for encapsulating hydrophobic quantum dots
      (QDs) into silica capsules with high photoluminescent (PL) efficiency. The
      process comprises three steps: silanization of QD surfaces, seed formation by
      assembly of the QDs, and coating of the QD seeds with a silica shell. Analysis of
      the encapsulation mechanism enabled this process to be adapted for application to
      CdSe-based core-shell QDs with various organic ligands such as oleic acid and
      with various emission wavelengths. Formation of the seeds is the key step in
      synthesizing the silica capsules, so that they have high PL efficiency. Due to
      the differences in QD size and in the affinity of the ligands on their surfaces,
      the concentration of QDs used in the synthesis must be optimized to maximize
      emission efficiency. Contrary to an initial assumption, several ligands remained
      on the QD surfaces even after the QDs were transferred from organic solution to
      water. This greatly affected the size and PL efficiency of the seeds. Judicious
      selection of the conditions for seed and silica capsule synthesis resulted in
      seeds with PL efficiency greater than 70% and in silica capsules encapsulating
      multiple CdSe/CdZnS QDs with PL efficiency as high as 41%. Silica capsules
      incorporating QDs with various emission peak wavelengths from green to red were
      also prepared. The process presented serves as a guideline for encapsulating
      various types of hydrophobic QDs into silica capsules for biological tagging
      applications. 

PMID- 24112845
TI  - Laparoscopic partial nephrectomy: An experience in 227 cases.
AB  - OBJECTIVE: To evaluate our long-term experience with laparoscopic partial
      nephrectomy (LPN) and to review the literature. MATERIAL AND METHODS: We
      performed a retrospective chart review, evaluating 227 consecutives laparoscopic
      partial nephrectomies performed between June 1995 and June 2010. Perioperative
      were recorded along with clinical a oncological outcomes. RESULTS: Mean age was
      56.4 years (18-87) and clinical stages were T1a, T1b and T2 in 90.74% (206/227),
      7.48% (17/227) and 1.76% (4/227), respectively. Median blood loss was 250 mL (10
      1800). The mean operative time was 108.42 minutes (30-240) and median warm
      ischemia time was 25 minutes (10-60). The intraoperative complication rate was
      2.64% (6/227), 5 (2.2%) secondary to bleeding. The postoperative complication
      rate was 5.72% (13/227) and bleeding is also the most frequent in 3% (7/227) of
      the cases. According to the Clavien classification, 1.32% (3/227), 0.88% (2/227)
      and 3.52% (8/227) were grade I, II and IIIb, respectively. The mean hospital stay
      was 3.66 days (1-12). Clear cell carcinoma was the most common histological
      finding in 74.6% (150 patients). TNM clasification was T1a, T1b y T2 in 90.74%
      (206/227), 7.48% (17/227) and 1,76% (4/227), respectively. No conversion or
      mortality was reported. Positive surgical margins were found in 4 patients
      (2.7%), with no local recurrence after long-term follow-up. At a mean follow up
      of 27 months, one patient had port site and peritoneal recurrence. CONCLUSION:
      Laparoscopic partial nephrectomy is a safe and viable alternative to open partial
      nephrectomy, providing equivalent oncologic outcomes and comparable morbidity to
      the traditional approach in experienced centers.

PMID- 24112846
TI  - Predicting native papilla biliary cannulation success using a multinational
      Endoscopic Retrograde Cholangiopancreatography (ERCP) Quality Network.
AB  - BACKGROUND: Success in deep biliary cannulation via native ampullae of Vater is
      an accepted measure of competence in ERCP training and practice, yet prior
      studies focused on predicting adverse events alone, rather than success. Our aim
      is to determine factors associated with deep biliary cannulation success, with/
      without precut sphincterotomy. METHODS: The ERCP Quality Network is a unique
      prospective database of over 10,000 procedures by over 80 endoscopists over
      several countries. After data cleaning, and eliminating previously stented or cut
      papillae, two multilevel fixed effect multivariate models were used to control
      for clustering within physicians, to predict biliary cannulation success, with
      and without allowing "precut" to assist an initially failed cannulation. RESULTS:
      13018 ERCPs were performed by 85 endoscopists (March 2007 - May 2011).
      Conventional (without precut) and overall cannulation rates were 89.8% and 95.6%,
      respectively. Precut was performed in 876 (6.7%). Conventional success was more
      likely in outpatients (OR 1.21), but less likely in complex contexts (OR 0.59),
      sicker patients (ASA grade (II, III/V: OR 0.81, 0.77)), teaching cases (OR 0.53),
      and certain indications (strictures, active pancreatitis). Overall cannulation
      success (some precut-assisted) was more likely with higher volume endoscopists (>
      239/year: OR 2.79), more efficient fluoroscopy practices (OR 1.72), and lower
      with moderate (versus deeper) sedation (OR 0.67). CONCLUSION: Biliary cannulation
      success appears influenced by both patient and practitioner factors. Patient- and
      case-specific factors have greater impact on conventional (precut-free)
      cannulation success, but volume influences ultimate success; both may be used to
      select appropriate cases and can help guide credentialing policies.

PMID- 24112847
TI  - Prognostic indicators of acute transverse myelitis in 39 children.
AB  - BACKGROUND: The Transverse Myelitis Consortium Working Group has proposed new
      diagnostic criteria for acute transverse myelitis. The purpose of the present
      study is to evaluate the relations between clinical variables and functional
      prognosis using new criteria. METHODS: We reviewed 39 Chinese cases meeting the
      new criteria, recorded clinical epidemiological data, and followed activities of
      daily living measuring scale (Modified Barthel Index). RESULTS: Thirty-nine
      children met new criteria for definite acute transverse myelitis in the past 14
      years between 1995 and 2008. Mean follow-up time was 102.7 months. Conversion to
      multiple sclerosis occurred in two patients (5.1%). Those children with a short
      time to maximal deficits, long time of peak neurological impairment and initial
      time of treatment, increased protein levels of the cerebrospinal fluid, and
      secondary infection were more likely to have residual neurological deficits,
      resulting in lower qualities of life (P = 0.005, P = 0.003, P = 0.011, P =
      0.0012, P = 0.000, respectively). CONCLUSIONS: A short time to maximal deficits,
      long time of peak neurological impairment and initial time of treatment,
      increased protein levels of cerebrospinal fluid, and secondary infection played
      important roles in predicting poor prognosis.

PMID- 24112848
TI  - Human periodontal ligament cell sheets cultured on amniotic membrane substrate.
AB  - OBJECTIVE: Periodontal ligament (PDL) cells and their substrates play key roles
      in periodontal regeneration. However, there has been no report on the use of
      amniotic membrane (AM) as a substrate for culturing PDL cells. In the current
      study, we conducted an analysis of PDL cells cultivated on AM to determine the
      distribution of factors responsible for maintaining the characteristics of PDL.
      MATERIALS AND METHODS: Amniotic membrane was obtained from women undergoing
      cesarean sections, whereas PDL tissue was obtained from human maxillary third
      molars. The harvested PDL cells were maintained in explant culture for three or
      four passages, following which they were cultured on AM. RESULTS: After 3 weeks
      of culture, the PDL cells had grown well on AM. Immunofluorescence showed that
      these cells were capable of proliferating and potentially maintaining their PDL
      like properties. In addition, strong cell-cell adhesion structures, namely
      desmosomes and tight junctions, were shown to be present between cells. Electron
      microscopy images showed that the cultured PDL cells had differentiated and
      proliferated on AM with lateral conjugation and adhesion to AM. CONCLUSION: We
      conclude that AM may represent a suitable substrate for culturing PDL cells and
      that PDL cells cultured on AM show sheet formation.

PMID- 24112849
TI  - Polyvictimization and its relationship to symptoms of psychopathology in a
      southern European sample of adolescent outpatients.
AB  - This study examined the relationship between accumulated experiences of
      victimization and symptoms of psychopathology in 132 adolescent outpatients aged
      12-17 years (M=14.27; SD=1.42). The Juvenile Victimization Questionnaire and the
      Youth Self-Report were used to analyze polyvictimization and symptoms of
      psychopathology, respectively. The interviews were conducted between December
      2009 and May 2012. Cluster analysis identified a subgroup of polyvictimized
      patients (n=17) whose general psychological impairment was significantly worse
      and who presented significantly more externalizing and internalizing symptoms in
      comparison to the rest of the sample. This difference remained significant when
      taking into account the clinical severity of these symptoms. These results should
      be taken into account when assessing and treating adolescent outpatients, for
      whom an adequate prognosis must be made in line with their experiences and
      distress. Both the self-report technique and the statistical procedure used have
      been shown to be suitable for identifying victimization experiences in
      outpatients, although this new evidence requires confirmation in future research.

PMID- 24112850
TI  - Residents' knowledge of standard drink equivalents: implications for screening
      and brief intervention for at-risk alcohol use.
AB  - BACKGROUND AND OBJECTIVES: Screening and brief intervention for reducing alcohol
      consumption has been demonstrated to be effective in various medical settings.
      The NIAAA has recommended that physicians screen all patients for at-risk and
      problem drinking. Often, screening is based on the concept of a "standard drink."
      METHODS: We administered a survey to residents (N=270) in order to assess their
      knowledge of standard drink equivalents and quantities of alcohol in various
      sizes of bottles. RESULTS: Although 89% of the responders stated that they had
      previously learned about screening for at-risk alcohol use, the majority did not
      know basic facts about standard drink equivalents. DISCUSSION AND CONCLUSIONS:
      Many trainees are not familiar with typical standard drink equivalents. This can
      have a significant impact on the screening of patients for problem drinking using
      screening tools that rely on standard drink equivalents.

PMID- 24112851
TI  - Life cycle assessment of energy from waste via anaerobic digestion: a UK case
      study.
AB  - Particularly in the UK, there is potential for use of large-scale anaerobic
      digestion (AD) plants to treat food waste, possibly along with other organic
      wastes, to produce biogas. This paper presents the results of a life cycle
      assessment to compare the environmental impacts of AD with energy and organic
      fertiliser production against two alternative approaches: incineration with
      energy production by CHP and landfill with electricity production. In particular
      the paper investigates the dependency of the results on some specific assumptions
      and key process parameters. The input Life Cycle Inventory data are specific to
      the Greater London area, UK. Anaerobic digestion emerges as the best treatment
      option in terms of total CO2 and total SO2 saved, when energy and organic
      fertiliser substitute non-renewable electricity, heat and inorganic fertiliser.
      For photochemical ozone and nutrient enrichment potentials, AD is the second
      option while incineration is shown to be the most environmentally friendly
      solution. The robustness of the model is investigated with a sensitivity
      analysis. The most critical assumption concerns the quantity and quality of the
      energy substituted by the biogas production. Two key issues affect the
      development and deployment of future anaerobic digestion plants: maximising the
      electricity produced by the CHP unit fuelled by biogas and to defining the future
      energy scenario in which the plant will be embedded. 

PMID- 24112852
TI  - Does the entity of scientific paper production render justice to a virtuous
      academic practice?

PMID- 24112853
TI  - Direct and indirect generation of waste in the Spanish paper industry.
AB  - The paper industry has a relatively high degree of reliance on suppliers when
      compared to other industries. Exploring the role of the paper industry in terms
      of consumption of intermediate inputs from other industries may help to
      understand how the production of paper does not only generate waste by itself but
      also affects the amount of waste generated by other industries. The product Life
      Cycle Assessment (LCA) is a useful analytical tool to examine and assess
      environmental impacts over the entire life cycle of a product "from cradle to
      grave" but it is costly and time intensive. In contrast, Economic Input Output
      Life Cycle Assessment Models (IO-LCA) that combine LCA with Input-Output analysis
      (IO) are more accurate and less expensive, as they employ publicly available
      data. This paper represents one of the first Spanish studies aimed at estimating
      the waste generated in the production of paper by applying IO-LCA. One of the
      major benefits is the derivation of the contribution of direct and indirect
      suppliers to the paper industry. The results obtained show that there was no
      direct relationship between the impact on output and the impact on waste
      generation exerted by the paper industry. The major contributors to waste
      generation were the mining industry and the forestry industry. 

PMID- 24112854
TI  - Prediction of future disposal of end-of-life refrigerators containing CFC-11.
AB  - The objective of this study was to predict the number of refrigerators containing
      CFC-11 blown isolation foam and the amount of CFC-11 banked in these
      refrigerators. By using a Weibull-based survival function, the number of CFC-11
      containing and still-functioning refrigerators was estimated to be approximately
      1.6 million in 2013 in Turkey. In order to determine the amount of CFC-11 in the
      isolation foam of these refrigerators, polyurethane (PU) foam samples were taken
      from a refrigerator manufactured in 1993 and the quantity of CFC-11 was analyzed
      by a GC-MS. It was determined that 113-195 mg CFC-11/g PU remains in the PU foam
      depending on the location such as door, sides, top and bottom. Knowing that a mid
      sized refrigerator contains 4 kg PU on average, the total amount of PU foam to be
      disposed of is 6344 tons when the CFC-11 containing refrigerators in Turkey
      become obsolete in the near future. Furthermore, 717-1237 tons of CFC-11 are
      expected to be banked in the PU foam of these refrigerators which will exert an
      equivalent amount of ozone depleting potential (ODP). In addition, the global
      warming potential will vary between 3.4 and 5.9 million tons of CO2.

PMID- 24112855
TI  - Measuring health literacy in populations: illuminating the design and development
      process of the European Health Literacy Survey Questionnaire (HLS-EU-Q).
AB  - BACKGROUND: Several measurement tools have been developed to measure health
      literacy. The tools vary in their approach and design, but few have focused on
      comprehensive health literacy in populations. This paper describes the design and
      development of the European Health Literacy Survey Questionnaire (HLS-EU-Q), an
      innovative, comprehensive tool to measure health literacy in populations.
      METHODS: Based on a conceptual model and definition, the process involved item
      development, pre-testing, field-testing, external consultation, plain language
      check, and translation from English to Bulgarian, Dutch, German, Greek, Polish,
      and Spanish. RESULTS: The development process resulted in the HLS-EU-Q, which
      entailed two sections, a core health literacy section and a section on
      determinants and outcomes associated to health literacy. The health literacy
      section included 47 items addressing self-reported difficulties in accessing,
      understanding, appraising and applying information in tasks concerning decisions
      making in healthcare, disease prevention, and health promotion. The second
      section included items related to, health behaviour, health status, health
      service use, community participation, socio-demographic and socio-economic
      factors. CONCLUSIONS: By illuminating the detailed steps in the design and
      development process of the HLS-EU-Q, it is the aim to provide a deeper
      understanding of its purpose, its capability and its limitations for others using
      the tool. By stimulating a wide application it is the vision that HLS-EU-Q will
      be validated in more countries to enhance the understanding of health literacy in
      different populations.

PMID- 24112856
TI  - A retrospective study of multimodal analgesic treatment after laparoscopic
      appendectomy in children.
AB  - BACKGROUND: Laparoscopic appendectomy is a common emergency pediatric surgery
      procedure accompanied by substantial pain (pain scores >4 for >60% of the time)
      in 33% of these patients. We introduced a bundle of pain management interventions
      including local anesthetic infiltration at the incision site, intravenous (IV)
      opioids by patient-controlled analgesia (PCA), and scheduled doses of IV
      ketorolac and oral acetaminophen/hydrocodone. OBJECTIVES: To evaluate the effect
      of these pain management interventions on pain control after laparoscopic
      appendectomy. METHODS: We retrospectively studied pain in 206 children above 7
      years of age undergoing laparoscopic appendectomy from December 2011 to February
      2012 at our institution. We extracted data on patient demographics, duration of
      anesthesia and surgery, intraoperative opioids, local anesthetic infiltration,
      surgical procedure reports, along with pain scores, postoperative PCA use, and
      opioid-related complications and hospital stays. Patients were divided into two
      groups - simple appendicitis without peritonitis and appendicitis with
      generalized peritonitis. RESULTS: The incidence of substantial pain when the
      multimodal regimen was used was 12%, which is significantly lower than earlier
      reports (Fisher's exact test P < 0.001). Patients with generalized peritonitis
      experienced more pain, consumed more opioids, had more unmet PCA demands, and a
      higher incidence of respiratory depression compared with those with simple
      appendicitis. CONCLUSION: The multimodal regimen of local anesthetic
      infiltration, opioid by PCA, NSAIDs, and oral acetaminophen/hydrocodone reduced
      the incidence of substantial pain. Additional studies are required to identify
      subgroups of patients with minimal opioid requirements who can benefit from
      modifications of this regimen.

PMID- 24112858
TI  - Reply: To PMID 23664629.

PMID- 24112857
TI  - Treatment of mouse liver slices with cholestatic hepatotoxicants results in down
      regulation of Fxr and its target genes.
AB  - BACKGROUND: Unexpected cholestasis substantially contributes to drug failure in
      clinical trials. Current models used for safety assessment in drug development do
      not accurately predict cholestasis in humans. Therefore, it is of relevance to
      develop new screening models that allow identifying drugs with cholestatic
      properties. METHODS: We employed mouse precision cut liver slices (PCLS), which
      were incubated 24 h with two model cholestatic compounds: cyclosporin A (CsA) and
      chlorpromazine (CPZ). Subsequently, transcriptome analysis using DNA microarrays
      and q-PCR were performed to identify relevant biological processes and
      biomarkers. Additionally, histology was carried out and levels of triglycerides
      (TG) and bile acids (BA) were measured. To verify the ex vivo mouse data, these
      were compared with publically available human data relevant for cholestasis.
      RESULTS: Whole genome gene expression analysis showed that CsA up-regulated
      pathways related to NF-kappaB, ER stress and inflammation. Both CsA and CPZ down
      regulated processes related to extracellular matrix (ECM) remodelling, BA
      homeostasis, Fxr signalling, and energy metabolism. The differential expression
      of a number of characteristic genes (e.g. Abcg5, Abcg8, Klf15, and Baat) could be
      confirmed by q-PCR. Histology revealed that CsA but not CPZ induced "ballooning"
      of hepatocytes. No effects on TG and BA levels were observed after incubation of
      PCLS with CsA and CPZ. A substantial number of processes altered in CsA- and CPZ
      treated mouse PCLS ex vivo was also found to be affected in liver biopsies of
      cholestatic patients. CONCLUSION: The present study demonstrated that mouse PCLS
      can be used as a tool to identify mechanisms of action of cholestatic model
      compounds. The induction of general stress responses and down-regulated Fxr
      signalling could play a role in the development of drug induced cholestasis.
      Importantly, comparative data analysis showed that the ex vivo mouse findings are
      also relevant for human pathology. Moreover, this work provides a set of genes
      that are potentially useful to assess drugs for cholestatic properties.

PMID- 24112859
TI  - Kikuchi disease in Connecticut.
AB  - Kikuchi disease is a self-limited disorder of unknown etiology characterized by
      focal painful lymphadenitis, fever, and weight loss that can be mistaken for
      malignancy. Diagnosis is established by node biopsy. Kikuchi disease is endemic
      in Asia; 10 cases have been reported in the US to date. We report 3 cases and
      review other US cases. 

PMID- 24112860
TI  - An anorexic girl with severe peripheral vasospasm.

PMID- 24112862
TI  - Routine surveillance ultrasound for the management of central venous catheters in
      neonates.
AB  - OBJECTIVES: To evaluate the frequency of central venous catheter (CVC)-related
      thrombi detected by routine surveillance ultrasound, and to assess whether
      positive findings had an impact on management or outcomes. STUDY DESIGN: All
      neonates in a tertiary neonatal intensive care unit who had a CVC inserted for
      >14 days underwent routine surveillance ultrasound biweekly between January 2003
      and December 2009. Data were reviewed retrospectively. RESULTS: Although all
      neonates were asymptomatic at time of surveillance ultrasound, 645 of the total
      1333 CVCs inserted in 1012 neonates underwent surveillance ultrasound, and
      thrombi were detected in 69 (10.7%). The CVCs with thrombi were more likely to be
      removed for nonelective reasons compared with CVCs without thrombi (59% vs 38%; P
      = .001; OR, 2.4, 95% CI 1.4-3.9). A total of 955 surveillance ultrasounds were
      performed to detect and monitor 69 CVCs with thrombi. The majority of thrombi
      were nonocclusive and nonprogressive. A change in management occurred in 8 cases
      of CVC-related thrombi (12%), or 1% of all screened cases. An average of 14
      ultrasounds were required to detect and monitor 1 CVC with thrombus, at a cost of
      $951 per CVC with thrombus and $8106 per case of CVC-related thrombi with a
      change in treatment. CONCLUSION: Asymptomatic thrombi were detected in a
      significant proportion of CVCs by routine surveillance ultrasound. There were
      significant costs, but infrequent changes to patient management.

PMID- 24112861
TI  - Vitamin D, race, and risk for anemia in children.
AB  - OBJECTIVE: To examine the association between 25-hydroxyvitamin D [25(OH)D]
      deficiency and anemia in a cohort of otherwise-healthy children and to determine
      whether race modifies the association between 25(OH)D status and hemoglobin
      (Hgb). STUDY DESIGN: Cross-sectional study of 10,410 children and adolescents
      ages 1-21 years from the 2001-2006 National Health and Nutrition Examination
      Survey. Anemia was defined as Hgb less than the 5th percentile for age and sex
      based on National Health and Nutrition Examination Survey III (1988-1994) data.
      RESULTS: Lower 25(OH)D levels were associated with increased risk for anemia; <30
      ng/mL, adjusted OR 1.93, 95% CI 1.21-3.08, P = .006, and <20 ng/mL, OR 1.47, 95%
      CI 1.14-1.89, P = .004. In linear regression, small but significant increases in
      Hgb were noted in the upper quartiles of 25(OH)D compared with the lowest
      quartile (<20 ng/mL) in the full cohort. Results of race-stratified linear
      regression by 25(OH)D quartile in white children were similar to those observed
      in the full cohort, but in black children, an increase in Hgb in the upper
      25(OH)D quartiles was only apparent compared with the lowest black race-specific
      quartile (<12 ng/mL). CONCLUSION: 25(OH)D deficiency is associated with increased
      risk of anemia in healthy US children, but the 25(OH)D threshold levels for lower
      Hgb are lower in black children in comparison with white children.

PMID- 24112863
TI  - Susceptibility-weighted imaging in pantothenate kinase-associated
      neurodegeneration.

PMID- 24112864
TI  - Mood disorders after traumatic brain injury in adolescents and young adults: a
      nationwide population-based cohort study.
AB  - OBJECTIVE: To delineate the relationship between traumatic brain injury (TBI) and
      mood disorders from population-based data in Taiwan. STUDY DESIGN: This
      prospectively followed cohort study involved a subset of the National Health
      Insurance Research Database containing complete inpatient and outpatient data of
      1 million randomly drawn beneficiaries. We included 10- to 24-year-old patients
      (n = 15,203) receiving the diagnosis of TBI in ambulatory visits or
      hospitalization from 2000-2004 and their age- and sex-matched comparison insureds
      using health service in the same year (n = 76,015). Diagnosis of mood disorders
      was recorded within 5 years after the traumatic event or index use of health
      service. Baseline demographics, clinical characteristics, and premorbid
      psychiatric conditions were compared using chi(2) analysis. Increased risk during
      the 5-year follow-up period was represented by crude and adjusted hazard ratios
      with 95% CI using a Cox proportional hazard regression. RESULTS: A total of
      451/15,203 patients with TBI (2.97%) received a diagnosis of mood disorders in
      the 5-year follow-up period compared with 1153/97,445 individuals (1.52%) without
      antecedent TBI. After adjusting for select premorbid comorbidities, TBI remained
      a significant predisposing factor with a 1.96-fold (95% CI 1.74-2.22) increase in
      risk of mood disorders. CONCLUSIONS: Our findings show a higher likelihood of
      manifesting mood disorders in adolescents and young adults who sustained a prior
      TBI. Health professionals should carefully monitor both the physical and
      psychological impacts of head trauma.

PMID- 24112865
TI  - Peristaltic waves in infantile hypertrophic pyloric stenosis.

PMID- 24112866
TI  - Suppressing childhood fever with antipyretics: inducing a false sense of
      security.

PMID- 24112867
TI  - Severe bacterial infection in patients with heterotaxy syndrome.
AB  - OBJECTIVE: To determine the incidence of sepsis in patients with heterotaxy
      syndrome. STUDY DESIGN: From our institutional database, we identified patients
      with heterotaxy syndrome and other complex congenital heart disease (CHD) born
      between 2001 and 2011. Severe bacterial infection was defined as sepsis with
      positive culture result or infection with abscess formation. RESULTS: We enrolled
      95 patients with heterotaxy syndrome (88 with right atrial isomerism and 7 with
      left atrial isomerism) and 142 patients with complex CHD. With 1026 person-years
      follow-up, the 5-year survival was 52% and 65.7% in heterotaxy and complex CHD
      groups, respectively (P = .239). Community-acquired severe bacterial infection
      occurred only in heterotaxy syndrome (13 episodes in 10 patients, 3 of whom had
      spleen noted at imaging study) with 2- and 5 years cumulative severe bacterial
      infection rate of 9.6% and 14.5%, respectively. The overall mortality rate of
      those with community-acquired severe bacterial infection was 31%. Pneumococcus
      and Citrobacter freundii were the most common pathogens. Nosocomial severe
      bacterial infection occurred in 33.3% of all patients and 12.5% of all
      procedures. The rates (0.59 and 0.52/100 hospitalization days in heterotaxy and
      complex CHD group) and the pathogens of nosocomial severe bacterial infection
      were similar between heterotaxy and complex CHD groups. CONCLUSIONS: Patients
      with heterotaxy syndrome are at high risk for community-acquired severe bacterial
      infection and also have high mortality rate whether the spleen is present or not.
      The risk of nosocomial severe bacterial infection seems similar to that of
      patients with other complex CHD.

PMID- 24112868
TI  - Not just a diaper rash: LUMBAR syndrome.

PMID- 24112869
TI  - Presence of varicose veins in cancer patients increases the risk for occurrence
      of venous thromboembolism.
AB  - BACKGROUND: Cancer patients are at increased risk of venous thromboembolism
      (VTE). OBJECTIVE: We investigated the association of a history of VTE,
      superficial thrombophlebitis, or the presence of varicose veins with the
      occurrence of VTE during the course of cancer. METHODS: Cancer patients were
      recruited in a prospective cohort study, the Vienna Cancer and Thrombosis Study.
      Patients who had VTE within 3 months before study inclusion were excluded. At
      study inclusion, history of VTE, history of superficial thrombophlebitis, and
      presence of varicose veins were recorded. Primary end point was the occurrence of
      symptomatic VTE. Hazard ratios were obtained using the competing risk analysis
      according to Fine and Gray. RESULTS: The cohort consisted of 1270 patients
      followed over a median of 590 days. A history of VTE was found in 66 patients
      (5.2%), superficial thrombophlebitis in 79 patients (6.2%), and varicose veins in
      160 patients (12.6%). Ninety-eight patients (7.7%) developed VTE during follow
      up. The hazard ratios for the risk of VTE in patients with a history of VTE or
      superficial thrombophlebitis were 1.44 (95% confidence interval: 0.67-3.07) and
      1.94 (1.04-3.61), respectively, and 2.01 (1.26-3.21) in those with varicose
      veins. In multivariable analysis including history of VTE, history of superficial
      thrombophlebitis, presence of varicose veins, and other patient-related factors,
      the presence of varicose veins (2.10 [1.29-3.41]) remained significantly
      associated with an increased risk of VTE. CONCLUSION: The presence of varicose
      veins is associated with an elevated risk of VTE in cancer patients. This
      clinical parameter could be useful for individual risk assessment of VTE in these
      patients.

PMID- 24112870
TI  - [Analysis of quality of life using the generic SF-36 questionnaire in patients
      with heart failure].
AB  - OBJECTIVE: Heart failure is one of the major chronic diseases that affect health
      related quality of life. The objective of this study was to evaluate the quality
      of life in patients with New York Heart Association functional class I-III using
      the SF-36 on a cohort of survivors of the EPICOUR Study Group and compare the
      quality of life with the general Spanish population of the same sex and age
      group. MATERIAL AND METHODS: A cohort study, observational, and prospective study
      was conducted on survivors of the EPICOUR Study Group, on whom a clinical
      progression-outcome review was performed along with the SF-36. RESULTS: The
      quality of life was studied in 50 patients (60% male). The average age of men was
      64.8 years and women 68.3. When analyzing the SF-36, it was observed that the
      results were lower in the physical dimensions than in the mental dimensions. The
      quality of life worsened with increasing functional class (statistically
      significant differences for scales of physical functioning, social functioning
      and borderline significance in mental health scale). When comparing patients with
      the general population of the same age and sex, patients with heart failure
      showed lower scores on all scales (significant differences in physical
      functioning, body pain, vitality, and social role for men, and physical function
      and emotional role for women). CONCLUSIONS: Heart failure causes a negative
      impact on quality of life, physical functioning, as well as psychosocial
      function, with the impairment becoming worse with increased functional class.

PMID- 24112871
TI  - Increased accumulation of magnetic nanoparticles by magnetizable implant
      materials for the treatment of implant-associated complications.
AB  - BACKGROUND: In orthopaedic surgery, accumulation of agents such as anti
      infectives in the bone as target tissue is difficult. The use of magnetic
      nanoparticles (MNPs) as carriers principally enables their accumulation via an
      externally applied magnetic field. Magnetizable implants are principally able to
      increase the strength of an externally applied magnetic field to reach also deep
      seated parts in the body. Therefore, the integration of bone-addressed
      therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant
      could improve the treatment of implant related infections. In this study a
      martensitic steel platelet as implant placeholder was used to examine its
      accumulation and retention capacity of MNPs in an in vitro experimental set up
      considering different experimental frame conditions as magnet quantity and
      distance to each other, implant thickness and flow velocity. RESULTS: The
      magnetic field strength increased to approximately 112% when a martensitic
      stainless steel platelet was located between the magnet poles. Therewith a
      significantly higher amount of magnetic nanoparticles could be accumulated in the
      area of the platelet compared to the sole magnetic field. During flushing of the
      tube system mimicking the in vivo blood flow, the magnetized platelet was able to
      retain a higher amount of MNPs without an external magnetic field compared to the
      set up with no mounted platelet during flushing of the system. Generally, a
      higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity
      of magnets and a lower distance between magnets led to a higher magnetic field
      strength. Albeit not significantly the magnetic field strength tended to increase
      with thicker platelets. CONCLUSION: A martensitic steel platelet significantly
      improved the attachment of magnetic nanoparticles in an in vitro flow system and
      therewith indicates the potential of magnetic implant materials in orthopaedic
      surgery. The use of a remanent magnetic implant material could improve the
      efficiency of capturing MNPs especially when the external magnetic field is
      turned off thus facilitating and prolonging the effect. In this way higher drug
      levels in the target area might be attained resulting in lower inconveniences for
      the patient.

PMID- 24112872
TI  - Attention network test: assessment of cognitive function in chronic fatigue
      syndrome.
AB  - Information processing difficulties are common in patients with chronic fatigue
      syndrome (CFS). It has been shown that the time it takes to process a complex
      cognitive task, rather than error rate, may be the critical variable underlying
      CFS patients' cognitive complaints. The Attention Network Task (ANT) developed by
      Fan and colleagues may be of clinical utility to assess cognitive function in
      CFS, because it allows for simultaneous assessment of mental response speed, also
      called information processing speed, and error rate under three conditions
      challenging the attention system. Comparison of data from two groups of CFS
      patients (those with and without comorbid major depressive disorder; n = 19 and
      22, respectively) to controls (n = 29) consistently showed that error rates did
      not differ among groups across conditions, but speed of information processing
      did. Processing time was prolonged in both CFS groups and most significantly
      affected in response to the most complex task conditions. For simpler tasks,
      processing time was only prolonged in CFS participants with depression. The data
      suggest that the ANT may be a task that could be used clinically to assess
      information processing deficits in individuals with CFS.

PMID- 24112873
TI  - Phylogeography and population structure of the biologically invasive
      phytopathogen Erwinia amylovora inferred using minisatellites.
AB  - Erwinia amylovora causes a major disease of pome fruit trees worldwide, and is
      regulated as a quarantine organism in many countries. While some diversity of
      isolates has been observed, molecular epidemiology of this bacterium is hindered
      by a lack of simple molecular typing techniques with sufficiently high
      resolution. We report a molecular typing system of E. amylovora based on variable
      number of tandem repeats (VNTR) analysis. Repeats in the E. amylovora genome were
      identified with comparative genomic tools, and VNTR markers were developed and
      validated. A Multiple-Locus VNTR Analysis (MLVA) was applied to E. amylovora
      isolates from bacterial collections representing global and regional distribution
      of the pathogen. Based on six repeats, MLVA allowed the distinction of 227
      haplotypes among a collection of 833 isolates of worldwide origin. Three
      geographically separated groups were recognized among global isolates using
      Bayesian clustering methods. Analysis of regional outbreaks confirmed presence of
      diverse haplotypes but also high representation of certain haplotypes during
      outbreaks. MLVA analysis is a practical method for epidemiological studies of E.
      amylovora, identifying previously unresolved population structure within
      outbreaks. Knowledge of such structure can increase our understanding on how
      plant diseases emerge and spread over a given geographical region. 

PMID- 24112874
TI  - Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of
      psychopathology in healthy twins at high and low risk for affective disorder.
AB  - Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective
      disorder. However, longitudinal studies evaluating a potential predictive role of
      BDNF on subsequent psychopathology are lacking. The aim of this study was to
      investigate whether BDNF alone or in interaction with the BDNF Val66Met
      polymorphism predict onset of affective disorder in healthy individuals at
      heritable risk for affective disorder. In a high-risk study, we assessed whole
      blood levels of BDNF in 234 healthy monozygotic and dizygotic twins with or
      without a co-twin history of affective disorder (high and low risk twins,
      respectively). Participants were followed up longitudinally with questionnaires
      at 6-month intervals for mean seven years and then reassessed with a personal
      interview to obtain information about whether they had developed psychiatric
      illness. At follow-up 36 participants (15.4%) had developed psychiatric disorder.
      Cox regression analysis revealed that BDNF levels at baseline were not associated
      with onset of illness in this explorative study. Further, two-way interactions
      between BDNF levels and the Val66Met polymorphism or between familial risk and
      the Val66Met polymorphism did not predict illness onset. 

PMID- 24112875
TI  - Light microscopic features and morphometry of sperm in the emu (Dromaius
      novaehollandiae).
AB  - A comprehensive morphologic description of emu sperm at the light microscopy
      level, an essential prerequisite for the routine evaluation of semen quality in
      this species, is not currently available. In this study, sperm morphology and
      morphometry were evaluated using conventionally prepared Romanowsky-stained semen
      smears of samples collected from the distal ductus deferens from 15 adult birds
      and fixed in 2.5% glutaraldehyde. Examination of the smears using phase contrast
      under 100* magnification readily resolved the various components of the cell,
      namely, the acrosome, nucleus, midpiece, principal piece, and endpiece. This
      technique was simple to use and produced consistently reproducible results.
      Normal emu sperm were typically filiform in appearance and closely resembled
      sperm of the ostrich and other non-passerine species, particularly poultry. A
      previously undescribed cytoplasmic appendage, associated with the base of the
      head, was a novel morphologic feature. The acrosome was short (1.84 +/- 0.31 MUm;
      mean +/- standard deviation), whereas the nucleus measured 11.77 +/- 0.93 MUm in
      length. The length of the segments of the flagellum were 2.91 +/- 0.4 MUm for the
      midpiece, 47.45 +/- 2.8 MUm for the principal piece, and 3.69 +/- 0.82 MUm for
      the endpiece. The total sperm length was 67.64 +/- 3.13 MUm (range, 60.14-79.49)
      and the head:tail ratio was 1:4. Sperm dimensions in the emu were similar to
      those of other ratites. 

PMID- 24112876
TI  - Smoking and osteoarthritis.

PMID- 24112878
TI  - [Benzodiazepine prescription in the elderly in different health care levels:
      characteristics and related factors].
AB  - OBJECTIVES: To determine the prevalence of benzodiazepine (BZD) prescription and
      the factors related to prescribing them in the elderly in the community, in an
      acute general hospital (AH) and in a convalescence geriatric unit (CGU). MATERIAL
      AND METHODS: Retrospective study of 334 CGU inpatients discharged from an AH. A
      comprehensive geriatric assessment included functional and cognitive evaluation
      before hospitalization, at admission and at discharge from CGU (Barthel index,
      Lawton index and Folstein Mini-Mental State Examination), as well as comorbidity
      (Charlson index), polypharmacy and social situation. The percentage of
      benzodiazepine prescriptions at the different healthcare levels was compared and
      their related factors were evaluated (Chi-squared test). RESULTS: The prevalence
      of benzodiazepine prescriptions in the community was 23.6%, and being female and
      polypharmacy were related factors to prescribing at this level. During AH
      admission, this proportion increased up to 38.6%, and after CGU admission
      decreased to 21.,9%. Factors related to prescription in AH were, being female,
      polypharmacy and osteoarticular-fracture related diagnosis, and in CGU, being
      female and polypharmacy. CONCLUSIONS: The prevalence of benzodiazepine
      prescribing was high among elderly people at every healthcare level (community,
      AH and CGU), and polypharmacy was one of the significant factors associated with
      prescribing. This prescribing was increased during AH admission due to a medical
      or surgical process.

PMID- 24112877
TI  - Exploring the role of auditory analysis in atypical compared to typical language
      development.
AB  - The relationship between auditory processing and language skills has been debated
      for decades. Previous findings have been inconsistent, both in typically
      developing and impaired subjects, including those with dyslexia or specific
      language impairment. Whether correlations between auditory and language skills
      are consistent between different populations has hardly been addressed at all.
      The present work presents an exploratory approach of testing for patterns of
      correlations in a range of measures of auditory processing. In a recent study, we
      reported findings from a large cohort of eleven-year olds on a range of auditory
      measures and the data supported a specific role for the processing of short
      sequences in pitch and time in typical language development. Here we tested
      whether a group of individuals with dyslexic traits (DT group; n = 28) from the
      same year group would show the same pattern of correlations between auditory and
      language skills as the typically developing group (TD group; n = 173). Regarding
      the raw scores, the DT group showed a significantly poorer performance on the
      language but not the auditory measures, including measures of pitch, time and
      rhythm, and timbre (modulation). In terms of correlations, there was a tendency
      to decrease in correlations between short-sequence processing and language
      skills, contrasted by a significant increase in correlation for basic, single
      sound processing, in particular in the domain of modulation. The data support the
      notion that the fundamental relationship between auditory and language skills
      might differ in atypical compared to typical language development, with the
      implication that merging data or drawing inference between populations might be
      problematic. Further examination of the relationship between both basic sound
      feature analysis and music-like sound analysis and language skills in impaired
      populations might allow the development of appropriate training strategies. These
      might include types of musical training to augment language skills via their
      common bases in sound sequence analysis.

PMID- 24112880
TI  - Principles of electrical stimulation of neural tissue.
AB  - Deep brain stimulation is a remarkable therapy that has mainstreamed electrical
      stimulation of the brain for the treatment of neurological dysfunction. To
      appreciate the mechanisms of deep brain stimulation, we need to understand the
      excitability of neural tissue. Here, we survey the pertinent principles of
      electrical excitation in the brain. The amount of current delivered and the
      tissue conductivity together determine the strength and extent of potentials
      generated by stimulation. The electrode-tissue interface is an important junction
      where electrical charge carriers in the stimulation hardware are converted to
      ionic charge carriers in the tissue. Cathodic stimulation tends to depolarize
      neural elements more easily than anodic stimulation. The current-distance
      relationship describes how the amount of current needed to excite an axon
      increases as a function of its distance from the electrode. This relationship
      also depends on the axon's diameter because large-diameter axons are excited more
      easily than small-diameter axons. For a given axon, the strength-duration
      relationship describes the inverse relationship between threshold current
      amplitude and pulse duration. Specific stimulation parameters must be considered
      to avoid stimulation-induced tissue damage. A strong foundation in these
      principles facilitates understanding of the complex effects of electrical
      stimulation in the brain. 

PMID- 24112879
TI  - Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass
      spectrometry (MALDI-MSI) reveals novel cancer-associated field effects.
AB  - Matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-MSI)
      is a rapidly advancing technique for intact tissue analysis that allows
      simultaneous localisation and quantification of biomolecules in different
      histological regions of interest. This approach can potentially offer novel
      insights into tumour microenvironmental (TME) biochemistry. In this study we
      employed MALDI-MSI to evaluate fresh frozen sections of colorectal cancer (CRC)
      tissue and adjacent healthy mucosa obtained from 12 consenting patients
      undergoing surgery for confirmed CRC. Specifically, we sought to address three
      objectives: (1) To identify biochemical differences between different
      morphological regions within the CRC TME; (2) To characterise the biochemical
      differences between cancerous and healthy colorectal tissue using MALDI-MSI; (3)
      To determine whether MALDI-MSI profiling of tumour-adjacent tissue can identify
      novel metabolic 'field effects' associated with cancer. Our results demonstrate
      that CRC tissue harbours characteristic phospholipid signatures compared with
      healthy tissue and additionally, different tissue regions within the CRC TME
      reveal distinct biochemical profiles. Furthermore we observed biochemical
      differences between tumour-adjacent and tumour-remote healthy mucosa. We have
      referred to this 'field effect', exhibited by the tumour locale, as cancer
      adjacent metaboplasia (CAM) and this finding builds on the established concept of
      field cancerisation. 

PMID- 24112881
TI  - Deep brain stimulation in animal models.
AB  - Deep brain stimulation (DBS) as a therapy in neurological and psychiatric
      disorders is applied widely. In this respect, DBS in animal models is performed
      to study the underlying mechanisms and to evaluate new indications and
      technology. This chapter summarizes our experience with DBS in animal models, and
      relevant literature. Electrodes for DBS in animal models have been developed
      using translational principles, to allow DBS under anesthesia and in freely
      moving conditions. The stimulation parameters have been adjusted for the animals
      using current density calculations. This paradigm of experimental DBS has been
      validated in a variety of animal models of neurological and psychiatric
      disorders. During the process of development and validation of DBS in animal
      models, specific problems have been encountered, which are discussed in the
      chapter. DBS in animal models is an adequate paradigm to explore the underlying
      mechanisms and new indications for DBS, and to refine DBS technology. 

PMID- 24112882
TI  - Deep brain stimulation surgical techniques.
AB  - Stereotactic techniques for placement of deep brain stimulation (DBS) electrodes
      have undergone continuous refinement since the introduction of human stereotaxis
      in the 1940s. Volumetric imaging techniques, including magnetic resonance imaging
      and computed tomography, have replaced ventriculography, and increasingly
      sophisticated computer systems now allow highly refined targeting of subcortical
      structures. This chapter reviews the underlying principles of stereotactic
      surgery, including imaging, targeting, and registration, and describes the
      surgical approach to DBS placement using both framed and frameless techniques. 

PMID- 24112883
TI  - Deep brain stimulation: how does it work?
AB  - Chronic deep brain stimulation (DBS) has become a widely accepted surgical
      treatment for medication-refractory movement disorders and is under evaluation
      for a variety of neurological disorders. In order to create opportunities to
      improve treatment efficacy, streamline parameter selection, and foster new
      potential applications, it is important to have a clear and comprehensive
      understanding of how DBS works. Although early hypothesis proposed that high
      frequency electrical stimulation inhibited neuronal activity proximal to the
      active electrode, recent studies have suggested that the output of the stimulated
      nuclei is paradoxically activated by DBS. Such regular, time-locked output is
      thought to override the transmission of pathological bursting and oscillatory
      activity through the stimulated nuclei, as well as inducing synaptic plasticity
      and network reorganization. This chapter reviews electrophysiological
      experiments, biochemical analyses, computer modeling and imaging studies positing
      that, although general principles exist, the therapeutic mechanism(s) of action
      depend both on the site of stimulation and on the disorder being treated. 

PMID- 24112884
TI  - Computational modeling of deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an effective clinical treatment for several
      medically refractory neurological disorders. However, even after decades of
      clinical success, explicit understanding of the response of neurons to applied
      electric fields remains limited, and scientific definition of the therapeutic
      mechanisms of DBS remains elusive. In addition, it is presently unclear which
      electrode designs and stimulation paradigms are optimal for maximal therapeutic
      benefit and minimal side-effects with DBS. Detailed computer modeling of DBS has
      emerged recently as a powerful technique to enhance our understanding of the
      effects of DBS and to create a virtual testing ground for new stimulation
      strategies. This chapter summarizes the fundamentals of neurostimulation
      modeling, presents some scientific contributions of computer models to the field
      of DBS, and demonstrates the application of DBS modeling tools to augment the
      clinical utility of DBS. 

PMID- 24112885
TI  - Therapeutic stimulation versus ablation.
AB  - The renaissance of functional stereotactic neurosurgery was pioneered in the mid
      1980s by Laitinen's introduction of Leksell's posteroventral pallidotomy for
      Parkinson's disease (PD). This ablative procedure experienced a worldwide spread
      in the 1990s, owing to its excellent effect on dyskinesias and other symptoms of
      post-l-dopa PD. Modern deep brain stimulation (DBS), pioneered by Benabid and
      Pollak in 1987 for the treatment of tremor, first became popular when it was
      applied to the subthalamic nucleus (STN) in the mid 1990s, where it demonstrated
      a striking effect on all cardinal symptoms of advanced PD, and permitted reduced
      dosages of medication. DBS, as a nondestructive, adaptable, and reversible
      procedure that is proving safe in bilateral surgery on basal ganglia, has great
      appeal to clinicians and patients alike, despite the fact that it is expensive,
      laborious, and relies on very strict patient selection criteria, especially for
      STN DBS. Psychiatric surgery has experienced the same phenomenon, with DBS
      supplanting completely stereotactic ablative procedures. This chapter discusses
      the pros and cons of ablation versus stimulation and investigates the reasons why
      DBS has overshadowed proven efficient ablative procedures such as pallidotomy for
      PD, and capsulotomy and cingulotomy for obsessive-compulsive disorder and
      depression. 

PMID- 24112886
TI  - Magnetic resonance imaging safety of deep brain stimulator devices.
AB  - Magnetic resonance imaging (MRI) has become the standard of care for the
      evaluation of different neurological disorders of the brain and spinal cord due
      to its multiplanar capabilities and excellent soft tissue resolution. With the
      large and increasing population of patients with implanted deep brain stimulation
      (DBS) devices, a significant proportion of these patients with chronic
      neurological diseases require evaluation of their primary neurological disease
      processes by MRI. The presence of an implanted DBS device in a magnetic resonance
      environment presents potential hazards. These include the potential for induction
      of electrical currents or heating in DBS devices, which can result in
      neurological tissue injury, magnetic field-induced device migration, or
      disruption of the operational aspects of the devices. In this chapter, we review
      the basic physics of potential interactions of the MRI environment with implanted
      DBS devices, summarize results from phantom studies and clinical series, and
      discuss present recommendations for safe MRI in patients with implanted DBS
      devices. 

PMID- 24112887
TI  - Brain stimulation and functional imaging with fMRI and PET.
AB  - The use of functional brain imaging techniques, including positron emission
      tomography (PET), single-photon emission computed tomography (SPECT), and
      functional magnetic resonance imaging (fMRI), has allowed for monitoring neuronal
      and neurochemical activities in the living human brain and identifying abnormal
      changes in various neurological and psychiatric diseases. Combining these methods
      with techniques such as deep brain stimulation (DBS) and transcranial magnetic
      stimulation (TMS) has greatly advanced our understanding of the effects of such
      treatment on brain activity at targeted regions as well as specific disease
      related networks. Indeed, recent network-level analysis focusing on inter
      regional covarying activities in data interpretation has unveiled several key
      mechanisms underlying the therapeutic effects of brain stimulation. However, non
      negligible discrepancies have been reported in the literature, attributable in
      part to the heterogeneity of both imaging and brain stimulation techniques. This
      chapter summarizes recent studies that combine brain imaging and brain
      stimulation, and includes discussion of future direction in these lines of
      research. 

PMID- 24112888
TI  - Deep brain stimulation for Parkinson's disease - patient selection.
AB  - Proper selection of patients who will reliably benefit from deep brain
      stimulation (DBS) is critical to its success. This requires careful evaluation
      that should be delivered by an expert multidisciplinary team involving a movement
      disorder neurologist, a neurosurgeon, a neuropsychologist, and a psychiatrist.
      The most suitable candidates for DBS suffer from Parkinson's disease with motor
      fluctuations and/or dyskinesias that are not adequately controlled with optimized
      medical therapy, or with medication-refractory tremor. During the best on-motor
      periods, gait difficulties, instability, and speech problems should be minimal,
      reflecting an excellent response to levodopa in the ideal candidate. The
      cognitive, psychiatric, and behavioral status must be normal or minimally
      affected, with the exception of dopamine agonist drug-induced impulse control
      disorders, which are usually improved after successful surgery and drug
      withdrawal. Moreover, the patients have no serious comorbidities. Most patients
      corresponding to this profile suffer from a relatively young onset of Parkinson's
      disease, and are aged less than 70 years at the time of surgery. Indeed, most
      patients fall outside this ideal description, and the medical art is to
      appreciate for each patient the extent to which the alterations of these features
      can be accepted. Eventually, patients make their own decision from detailed
      information of their individualized risks and benefits of DBS. Patient
      expectations, cooperation, and familial support are also important
      considerations. 

PMID- 24112889
TI  - Clinical outcome of deep brain stimulation for Parkinson's disease.
AB  - Deep brain stimulation is one of the most effective treatments of Parkinson's
      disease (PD). This report summarizes the state of the art as at January 2013.
      Stimulation of the subthalamic nucleus is the most commonly used approach. It
      improves the core motor symptoms better than medication in patients with advanced
      disease. It also improves the majority of nonmotor symptoms, such as mood,
      impulse control disorders, sleep, and some autonomic dysfunctions. Quality of
      life (QoL) is improved significantly more than with medication. Long-term data
      show that the treatment is effective for up to 10 years, but the late appearance
      of l-dopa-resistant symptoms is seemingly not influenced. Internal globus
      pallidus (GPi) stimulation is less well studied but seems to have similar short
      term efficacy. Importantly l-dopa use cannot be reduced with GPi DBS, which is a
      major disadvantage for patients suffering from medication side-effects, although
      gait may be influenced more positively. Although short-term QoL improvement seems
      to be similar to that for subthalamic nucleus (STN) DBS - gait and speech may be
      better improved - long-term data are rare for GPi DBS. Thalamic stimulation in
      the ventral intermediate nucleus (VIM) is applied only in tremor-dominant elderly
      patients. The treatment improves the dopa-sensitive symptoms and effectively
      reduces fluctuations leading to an overall QoL improvement. Although most of the
      controlled studies have been on advanced PD, the recently published EARLYSTIM
      study suggests that even patients with a very short duration of their
      fluctuations and dyskinesia are doing significantly better with neurostimulation
      in terms of QoL and all major motor outcome parameters. 

PMID- 24112890
TI  - Postoperative management of deep brain stimulation in Parkinson's disease.
AB  - Deep brain stimulation has become an established treatment for advanced
      Parkinson's disease. Its postoperative management is a delicate phase, dedicated
      to finding the optimal balance between stimulation and dopaminergic treatment.
      Postoperative management can be divided into an acute phase, aimed at the
      selection of the best stimulation contact, and a stabilization phase, aimed at
      the progressive adjustment of stimulation parameters and medications. A good
      knowledge of the electrophysiological anatomy of the target and surrounding
      structures, of the potential consequences of dopaminergic treatment
      modifications, and of the time course and interactions between stimulation and
      medication effects is mandatory for optimal outcome. This chapter focuses on the
      main strategies for the acute and chronic management of stimulation parameters
      and medication in the three main nuclei targeted in Parkinson's disease, namely
      the subthalamic nucleus, the ventral intermediate thalamic nucleus, and the
      internal part of the globus pallidus. 

PMID- 24112891
TI  - Psychiatric considerations in deep brain stimulation for Parkinson's disease.
AB  - Deep brain stimulation targeting the subthalamic nucleus or globus pallidus
      internus are highly effective for the symptomatic treatment of Parkinson's
      disease. The assessment and management of psychiatric issues is relevant to
      preoperative patient selection and to optimal postoperative outcomes. This
      chapter reviews the evidence on psychiatric symptoms in the perioperative state
      including suicidal behaviors, depression, anxiety, mania, apathy, and impulse
      control disorders. 

PMID- 24112892
TI  - Deep brain stimulation for essential tremor.
AB  - Essential tremor is the most common tremor disorder and is characterized by a
      postural and kinetic tremor. Most commonly, the disease involves the upper
      extremities, although other body parts may be affected. Essential tremor is seen
      most often in adults and may markedly limit abilities to perform daily
      activities. Medications often fail to control the tremor adequately. In the past,
      ventral intermediate nucleus of the thalamus (VIM) thalamotomy was the surgery of
      choice for medication-resistant patients with disabling tremor. With
      technological advances, deep brain stimulation (DBS) to the VIM has replaced
      thalamotomy as the operation of choice for patients with essential tremor, given
      the heightened risk of permanent neurological deficits associated with ablative
      surgery. Multiple studies have demonstrated that unilateral VIM DBS has
      significant short- and long-term benefits for targeted tremor. Unilateral VIM DBS
      may also improve head and voice tremor, although most commonly bilateral
      stimulation is required for adequate control. However, bilateral thalamic
      stimulation is associated with a higher incidence of neurological deficits,
      particularly speech and gait problems. Investigations of DBS of other brain
      target areas for essential tremor, such as the posterior subthalamic area and the
      subthalamic nucleus, are ongoing. 

PMID- 24112893
TI  - Deep brain stimulation for dystonia.
AB  - The few reported controlled studies show that bilateral stimulation of the globus
      pallidus interna (GPi) is a safe and effective long-term treatment for
      hyperkinetic disorders. However, the recently published data on deep brain
      stimulation (DBS) applied to different targets or patients (especially those with
      secondary dystonia) are mainly uncontrolled case reports, precluding a clear
      determination of its efficacy, and providing little guidance as to the choice of
      a "good" target in a "good" patient. This chapter reviews the literature on DBS
      in primary dystonia, paying particular attention to the risk:benefit ratio in
      focal and segmental dystonias (cervical dystonia, cranial dystonia) and to the
      predictive factors for a good outcome. The chapter also highlights recent data on
      the marked benefits of the technique in myoclonus dystonia (in which pallidal, as
      opposed to thalamic, stimulation is more effective) and in tardive dystonia
      dyskinesia. Although, the decision to treat appears relatively straightforward in
      patients with primary dystonia, myoclonus-dystonia, and tardive dystonia who have
      a normal findings on magnetic resonance imaging and normal cognitive function,
      there are still no reliable tools to help predict the timescale of postoperative
      benefit. This chapter provides a comprehensive analysis of the use of the
      treatment in various types of secondary dystonia, with little to moderate benefit
      in most cases, based on single cases or small series. Beyond the reduction in the
      severity of dystonia, the global motor and functional outcome is difficult to
      determine owing to the paucity of adequate evaluation tools. Because of the large
      interpatient variability, different targets may be effective depending on the
      symptoms in each individual. 

PMID- 24112894
TI  - Role of deep brain stimulation in the treatment of secondary dystonia-dyskinesia
      syndromes.
AB  - Dystonia-dyskinesia syndromes (DDS) are severe disabling movement disorders,
      characterized by twisting and repetitive movements or abnormal postures. Movement
      disorders are differentiated as primary or secondary. Primary movement disorders
      are of genetic or idiopathic origin, whereas secondary forms result from
      exogenous injuries. A PubMed literature search identified 32 clinical research
      studies reporting on a total of 153 patients with secondary dystonia treated with
      deep brain stimulation. For 116 patients, the mean Burke-Fahn-Marsden Dystonia
      Rating Scale (BFMDRS) score improved by 49%. The greatest mean BFMDRS improvement
      was achieved for tardive dyskinesia. The majority of patients were implanted in
      the globus pallidus. Fewer patients received thalamic or subthalamic nucleus
      stimulation. Electrical neuromodulation of subcortical structures can be very
      useful for a small number of patients with movement disorders due to a structural
      damage of the brain. 

PMID- 24112895
TI  - Deep brain stimulation for other tremors, myoclonus, and chorea.
AB  - Deep brain stimulation (DBS) is a well established treatment for essential tremor
      and for the tremor associated with Parkinson's disease. The efficacy of DBS in
      these common tremors has led some investigators to apply the technique to rarer
      tremors such as such as Holmes' tremor, posttraumatic tremor, orthostatic tremor,
      and the tremor associated with multiple sclerosis. Likewise, DBS of the thalamus
      and globus pallidus directly suppresses levodopa-induced dyskinesias in
      Parkinson's disease, suggesting the application of DBS to other hyperkinetic
      states such as Huntington's disease, tardive dyskinesia, and hemiballism.
      Myoclonus has also been treated with DBS, especially in cases where it is
      associated with dystonia. This chapter reviews the reported results of DBS for
      these conditions. Due to the rarity of these indications, most of the literature
      reviewed takes the form of case reports or small single-center case series. 

PMID- 24112896
TI  - Deep brain stimulation for epilepsy.
AB  - Deep brain stimulation for seizures has been applied to cerebellum, caudate,
      locus coeruleus, subthalamic nucleus, mammillary bodies, centromedian thalamus,
      anterior nucleus of thalamus, hippocampus and amygdala, hippocampal commissure,
      corpus callosum, neocortex, and occasionally to other sites. Animal and clinical
      studies have primarily investigated seizure prevention and, to a lessersmaller
      extent, seizure interruption. No studies have yet shown stimulation able to cure
      epilepsy. A wide variety of stimulation parameters have been employed in multiple
      different combinations of frequencies, amplitudes, and durations. Literature
      review identifies at least 52 clinical studies of brain stimulation for epilepsy
      in 817 patients. Two studies were large, randomized, and controlled, one in the
      anterior nucleus of thalamus and another at the cortical or hippocampal seizure
      focus; both of these studies showed efficacy and tolerability of stimulation.
      Many questions remain. We do not know the mechanisms, the best stimulation
      parameters, the best patient population, or how to predict benefit in advance. We
      do not know why benefit of neurostimulation for epilepsy seems to increase over
      time or whether there are long-term deleterious effects. All of these questions
      may be answerable with a combination of laboratory research and clinical
      experience. 

PMID- 24112897
TI  - Deep brain stimulation for major depression.
AB  - A third of patients suffering from major depression cannot be helped by
      conventional treatment methods. These patients face reduced quality of life, high
      risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is
      under scientific evaluation as a new treatment option for these treatment
      resistant patients. First clinical studies with small samples have been
      stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the
      capsula interna (ALIC), and the nucleus accumbens (NAcc). Long-term
      antidepressant effects, augmentation of social functioning, and normalization of
      brain metabolism have been shown in about 50% of patients. Cognitive safety
      regarding attention, learning, and memory has been reported. Adverse events were
      wound infection, suicide, and hypomania, amongst others. Larger studies are under
      way to confirm these preliminary encouraging results. New hypothesis-guided
      targets (e.g., medial forebrain bundle, habenula) are about to be assessed in
      clinical trials. The application of DBS for other psychiatric diseases (e.g.,
      bipolar disorder, alcohol dependency, opioid addiction, schizophrenia) is debated
      and single case studies are under way. Standards are needed for study
      registration, target selection, patient inclusion and monitoring, and publication
      of results to guarantee safety for the patients and scientific exchange. 

PMID- 24112898
TI  - Deep brain stimulation in obsessive-compulsive disorder: neurocircuitry and
      clinical experience.
AB  - The last decade has seen a significant rise in interest in the use of deep brain
      stimulation (DBS) for the management of obsessive-compulsive disorder (OCD), one
      of psychiatry's most challenging conditions. The prominent role of both thought
      (obsessions) and motor (compulsions) dysfunction in OCD place the condition at
      the border between the neurological and the psychiatric. This is supported by a
      growing body of literature that implicates structures in decision-making, reward,
      and action-selection circuits in the disorder. Here, we provide an overview of
      the neurocircuitry of OCD while reviewing the DBS literature to date for the
      condition. Results of DBS trials in treatment- resistant OCD have been remarkably
      similar, with clinical response rates in the range of 40-60%, despite the use of
      a diverse range of targets. These results imply that a common underlying circuit
      is being modulated, and moreover that there is room for improvement, and debate,
      in the development of an evidence-driven DBS treatment for this chronic,
      debilitating illness. 

PMID- 24112899
TI  - Deep brain stimulation for Tourette syndrome.
AB  - Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal
      tics, often associated with behavioral disorders, with typical onset in early
      childhood. In most patients, the symptoms decrease spontaneously when adulthood
      is reached, or can be treated with behavioral therapy or medication. Only a small
      proportion of patients are candidates for surgical treatment. In 1999, thalamic
      deep brain stimulation (DBS) was introduced for intractable Tourette syndrome.
      Since then, a diversity of targets have been used, located mainly at the level of
      the medial part of the thalamus, in the globus pallidus internus (anteromedial
      limbic and posteroventrolateral motor part), the globus pallidus externus, and
      the internal capsule/nucleus accumbens. The pathophysiology of Tourette syndrome
      is still a matter of considerable debate. Current knowledge of cortical-basal
      ganglia-thalamocortical circuits provides explanations for the beneficial effects
      of DBS on tics. Inclusion and exclusion criteria have been formulated to identify
      good candidates for DBS. Because of the small number of patients, there is a
      strong need for multicenter double-blind trials with standard protocols. 

PMID- 24112900
TI  - Deep brain stimulation in addiction due to psychoactive substance use.
AB  - Addiction is one of the most challenging health problems. It is associated with
      enormous individual distress and tremendous socioeconomic consequences.
      Unfortunately, its underlying mechanisms are not fully understood, and
      pharmacological, psychological, or social interventions often fail to achieve
      long-lasting remission. Next to genetic, social, and contextual factors, a
      substance-induced dysfunction of the brain's reward system is considered a
      decisive factor for the establishment and maintenance of addiction. Due to its
      successful application and approval for several neurological disorders, deep
      brain stimulation (DBS) is known as a powerful tool for modulating dysregulated
      networks and has also been considered for substance addiction. Initial promising
      case reports of DBS in alcohol and heroin addiction in humans have recently been
      published. Likewise, results from animal studies mimicking different kinds of
      substance addiction point in a similar direction. The objective of this review is
      to provide an overview of the published results on DBS in addiction, and to
      discuss whether these preliminary results justify further research, given the
      novelty of this treatment approach. 

PMID- 24112901
TI  - Evaluating the potential of deep brain stimulation for treatment-resistant
      anorexia nervosa.
AB  - Anorexia nervosa is a chronic and debilitating psychiatric disorder associated
      with one of the highest mortality rates of any psychiatric condition. Despite
      advances in neuroimaging, genetics, pharmacology, and psychosocial interventions
      in the last half-century, little progress has been made in altering the natural
      history of the condition or its outcomes. Evidence is now emerging that the
      condition is, at least in part, maintained by dysfunctional activity in key
      neuroanatomic circuits subserving illness-maintaining symptoms. Abnormal reward
      processing, compulsive hyperactivity, chronic anxiety, and depression, all
      suggest that anorexia nervosa shares much in common with other conditions, such
      as major depression and obsessive-compulsive disorder, for which surgical therapy
      with deep brain stimulation (DBS) has been tried, with promising results. As a
      result, the use of DBS in treatment-resistant anorexia nervosa should be
      evaluated in carefully designed, early-phase feasibility trials. 

PMID- 24112902
TI  - Deep brain stimulation for pain.
AB  - Deep brain stimulation (DBS) is a neurosurgical intervention whose efficacy,
      safety, and utility have been shown in the treatment of movement disorders. For
      the treatment of chronic pain refractory to medical therapies, many prospective
      case series have been reported, but few have published findings from patients
      treated during the past decade using current standards of neuroimaging and
      stimulator technology. We summarize the history, science, selection, assessment,
      surgery, and personal clinical experience of DBS of the ventral posterior
      thalamus, periventricular/periaqueductal gray matter, and, latterly, the rostral
      anterior cingulate cortex (Cg24) in 100 patients treated now at two centers (John
      Radcliffe Hospital, Oxford, UK, and Hospital de Sao Joao, Porto, Portugal) over
      12 years. Several experienced centers continue DBS for chronic pain with success
      in selected patients, in particular those with pain after amputation, brachial
      plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other
      successes include pain after multiple sclerosis and spine injury. Somatotopic
      coverage during awake surgery is important in our technique, with cingulate DBS
      considered for whole-body pain or after unsuccessful DBS of other targets.
      Findings discussed from neuroimaging modalities, invasive neurophysiological
      insights from local field potential recording, and autonomic assessments may
      translate into improved patient selection and enhanced efficacy, encouraging
      larger clinical trials. 

PMID- 24112903
TI  - Central thalamic deep brain stimulation for support of forebrain arousal
      regulation in the minimally conscious state.
AB  - This chapter considers the use of central thalamic deep brain stimulation
      (CT/DBS) to support arousal regulation mechanisms in the minimally conscious
      state (MCS). CT/DBS for selected patients in a MCS is first placed in the
      historical context of prior efforts to use thalamic electrical brain stimulation
      to treat the unconscious clinical conditions of coma and vegetative state. These
      previous studies and a proof of concept result from a single-subject study of a
      patient in a MCS are reviewed against the background of new population data
      providing benchmarks of the natural history of vegetative and MCSs. The
      conceptual foundations for CT/DBS in selected patients in a MCS are then
      presented with consideration of both circuit and cellular mechanisms underlying
      recovery of consciousness identified from empirical studies. Directions for
      developing future generalizable criteria for CT/DBS that focus on the integrity
      of necessary brain systems and behavioral profiles in patients in a MCS that may
      optimally response to support of arousal regulation mechanisms are proposed. 

PMID- 24112904
TI  - Deep brain stimulation for cognitive disorders.
AB  - Disorders of cognition are a major societal burden. As the population grows and
      ages, these conditions demand urgent attention, as healthcare resources stretch
      to accommodate the growing number of patients. Although much is known about the
      neurobiology of dementia and Alzheimer's disease (AD), few treatments are
      available to arrest or slow down the illness. By targeting specific structures
      within known circuits, deep brain stimulation (DBS) can have effects across
      memory and cognitive networks, and is therefore a potentially promising avenue
      for novel dementia treatments. This chapter reviews the literature on DBS for AD
      and dementia associated with Parkinson's disease, and highlight some of the
      neuroanatomical targets that offer the most promise in modulating the underlying
      pathological activity in brain circuitry. 

PMID- 24112905
TI  - Ethics guidance for neurological and psychiatric deep brain stimulation.
AB  - The consideration of ethical and social issues related to current uses of deep
      brain stimulation (DBS) as well as investigational uses should now be an integral
      part of contemporary DBS practice. Scholarship, interdisciplinary work groups,
      and peer processes have helped articulate standards that need to be respected and
      implemented in current DBS practice. Integrating new knowledge and
      interdisciplinary ethical perspectives could be considered a sign of the maturity
      and rigor of a DBS program. Still, investigational uses of DBS carry tremendous
      hope but also touch on sensitive and thorny ethical questions. These questions
      can benefit from the ethical wisdom generated for standard uses of DBS but also
      challenge current practices and professional conduct. Realizing this,
      interdisciplinary expert groups have been convened to identify and flesh out
      ethical guideposts for cutting-edge research in DBS. By implementing these
      ethical frameworks, DBS is an opportunity to develop promising treatments for a
      set of vulnerable and sometimes underserved patients while keeping their best
      interests in sight. 

PMID- 24112906
TI  - Transcranial electric and magnetic stimulation: technique and paradigms.
AB  - Transcranial electrical and magnetic stimulation techniques encompass a broad
      physical variety of stimuli, ranging from static magnetic fields or direct
      current stimulation to pulsed magnetic or alternating current stimulation with an
      almost infinite number of possible stimulus parameters. These techniques are
      continuously refined by new device developments, including coil or electrode
      design and flexible control of the stimulus waveforms. They allow us to influence
      brain function acutely and/or by inducing transient plastic after-effects in a
      range from minutes to days. Manipulation of stimulus parameters such as pulse
      shape, intensity, duration, and frequency, and location, size, and orientation of
      the electrodes or coils enables control of the immediate effects and after
      effects. Physiological aspects such as stimulation at rest or during attention or
      activation may alter effects dramatically, as does neuropharmacological drug co
      application. Non-linear relationships between stimulus parameters and
      physiological effects have to be taken into account. 

PMID- 24112907
TI  - Epidural and subdural stimulation.
AB  - Cortical stimulation, either transcranial or by means of electrodes implanted
      epidurally or subdurally, is used increasingly to treat neuropsychiatric
      diseases. In cases where transcranial stimulation gives only short-term success,
      implanted electrodes can yield results that are similar but long-term. Epidural
      stimulation is used widely to treat chronic neuropathic pain, whereas newer
      fields are in movement disorders, tinnitus, depression, and functional
      rehabilitation after stroke. For epidural stimulation, computational models
      explain the geometry of stimulation parameters (anodal, cathodal, and bifocal)
      and are used for targeting to yield the best clinical results. Nevertheless, the
      role of the cerebrospinal fluid layer also has to be taken into consideration.
      Subdural or intrasulcal stimulation allows a more focused stimulation with lower
      current intensities. This advantage, however, is counterbalanced by a higher
      complication rate with regard to epileptic seizures, subdural or intracerebral
      hemorrhages, and wound infections. 

PMID- 24112908
TI  - Physics of effects of transcranial brain stimulation.
AB  - The effects of transcranial stimulation are determined to a large extent by the
      spatial distribution and temporal variation of the electric field produced in the
      brain. In this chapter, we first describe some of the factors that affect the
      electric field in the brain generally, such as the effect of tissue heterogeneity
      and anisotropy, or focality. These are common to transcranial magnetic
      stimulation (TMS) and to several forms of transcranial current stimulation (tCS),
      such as transcranial direct current stimulation (tDCS), transcranial alternating
      current stimulation (tACS), and transcranial random noise stimulation (tRNS).
      Then the main features of the electric field in the human brain during TMS and
      tCS are presented. This knowledge is important to predict the location and extent
      of the stimulated region as well as the stimulation intensity in the brain. 

PMID- 24112909
TI  - Biological effects of non-invasive brain stimulation.
AB  - By incorporating the known physiology of the spinal cord epidural activity evoked
      by single-pulse, paired-pulse, and repetitive transcranial magnetic stimulation
      (TMS) with the anatomical and computational characteristics of the canonical
      model of the cerebral cortex circuit, and composed of layer II and III and layer
      V excitatory pyramidal cells, inhibitory interneurons, corticocortical and
      thalamocortical inputs, the characteristics and nature of the corticospinal
      activity evoked by TMS including its regular and rhythmic nature, the dose
      dependence, and pharmacological modulation of the discharge might be explained
      elegantly. TMS inducing strong depolarization of the superficial excitatory cells
      of the circuit may lead to the recruitment of fully synchronized clusters of
      excitatory neurons, including layer V pyramidal tract neurons (PTNs), and
      inhibitory neurons producing a high-frequency (~670Hz) repetitive discharge of
      the corticospinal axons. The role of the inhibitory circuits is crucial to
      entrain the firing of the excitatory networks to produce a high-frequency
      discharge. The integrative properties of the circuit might also provide a good
      framework for interpretation of the changes in corticospinal activity produced by
      paired and repetitive TMS. The changes can be produced presynaptically to PTN
      cells or at the level of these cells, depending mainly on the intensity of
      magnetic stimuli. 

PMID- 24112910
TI  - Central motor conduction time.
AB  - Central motor conduction time (CMCT) is the time taken for neural impulses to
      travel through the central nervous system on their way to the target muscles.
      When the motor cortex is stimulated with transcranial magnetic stimulation (TMS),
      CMCT is calculated by subtracting the peripheral conduction time from the motor
      evoked potential latency elicited by motor cortical TMS. CMCT in infants and
      children reaches adult level at about age of 6 years for the lower limbs. The
      alterations of CMCT in various neurological conditions are reviewed in this
      chapter. Prolongation of CMCT occurs due to slowing of conduction through rapidly
      conducting corticospinal fibers, as seen in various disorders such as
      demyelinating diseases (multiple sclerosis, MS), amyotrophic lateral sclerosis,
      structural lesions in the corticospinal tract such as stroke and compressive
      myelopathy, and neurodegenerative disorders including multiple system atrophy and
      progressive supranuclear palsy. As CMCT is prolonged in certain clinical
      conditions, it is of diagnostic value in some neurological disorders such as
      myelopathy, amyotrophic lateral sclerosis, and MS when used together with other
      clinical and electrophysiological measures. It could also be used as a prognostic
      marker in some of neurological conditions, such as myelopathy and MS. 

PMID- 24112911
TI  - Pharmaco-transcranial magnetic stimulation studies of motor excitability.
AB  - Application of a single dose of a central nervous system (CNS) active drug with a
      defined single mode of action has been proven useful to explore and characterize
      the pharmacophysiological properties of transcranial magnetic stimulation (TMS)
      measures of motor cortical and corticospinal excitability in humans. With this
      pharmaco-TMS approach, it was demonstrated that different TMS measures reflect
      axon excitability (motor threshold), or inhibitory (cortical silent period, short
      interval intracortical inhibition, long-interval intracortical inhibition, short
      latency afferent inhibition) or excitatory synaptic excitability (motor evoked
      potential amplitude, intracortical facilitation, short-interval intracortical
      facilitation) of distinct neuronal elements in the CNS. Pharmaco-TMS has opened
      an exciting window into human cortical physiology. The array of
      pharmacophysiologically well defined TMS measures is now used by neurologists,
      psychiatrists, and clinical neurophysiologists for diagnosis or treatment
      monitoring in neuropsychiatric disease. This chapter reviews systematically the
      TMS measures of motor cortical and corticospinal excitability from the
      perspective of pharmacophysiological characterization. For example, it is
      demonstrated that blockers of voltage-gated sodium channels specifically increase
      motor threshold but do not alter other TMS measures of excitability, whereas
      positive modulators at gamma-butyric acid (GABA) type A receptors, such as
      benzodiazepines, enhance short-interval intracortical inhibition and depress
      motor evoked potential amplitude but have no effect on motor threshold. 

PMID- 24112912
TI  - Treating the depressions with superficial brain stimulation methods.
AB  - Many, if not most, of the different superficial brain stimulation methods are
      being either used or investigated to treat the depressions. There are likely many
      reasons why there is this much interest and research involving brain stimulation
      treatments for depression, including that the depressions are common, there is
      dissatisfaction with other treatments, and some patients do not respond to
      medications or talking therapies. This is coupled with the fact that depressive
      episodes are a periodic or temporary state of the brain, and that when patients
      are no longer in that state they return to normal functioning. Additionally, the
      oldest brain stimulation method, electroconvulsive therapy (ECT), is also the
      most effective antidepressant available for the acute treatment of depression in
      patients who do not respond to medications. The newer brain stimulation methods
      have followed in the path blazed by ECT, showing that stimulation of key regions
      can cause a change in brain state and treat the depression. After almost 20 years
      of research, repeated daily repetitive transcranial magnetic stimulation (rTMS)
      of the prefrontal cortex for several weeks is now also an established clinical
      treatment for acute episodes. The data are less convincing for the other brain
      stimulation methods, but all are being investigated. Using brain stimulation (as
      opposed to medications or talking therapy) to treat depression is a rapidly
      expanding area of research with already established clear indications. Much more
      work is needed to understand best which methods should be used in any given
      patient, and in what order. 

PMID- 24112913
TI  - Other therapeutic psychiatric uses of superficial brain stimulation.
AB  - The majority of literature on superficial brain stimulation for the treatment of
      psychiatric conditions is focused on transcranial magnetic stimulation (TMS) for
      major depressive disorder. Given its versatility and mode of action, TMS use has
      been now extended to other psychiatric disorders including anxiety disorders,
      bipolar disorder, psychotic disorders, and disorders of executive function. In
      this chapter we review the rationale and available evidence for the use of TMS as
      a treatment option in conditions other than major depression - post-traumatic
      stress disorder, obsessive-compulsive disorder, panic disorder, generalized
      anxiety disorder, attention-deficit/hyperactivity disorder, catatonia,
      schizophrenia, and bipolar disorder. Although the rationale for its use in the
      treatment of the above-mentioned conditions is strong, the available evidence is
      mixed and limited. At this juncture no definitive conclusions or recommendations
      can be drawn; however, given the existing positive signals and the significant
      limitations of the presented evidence, further research is warranted to assess
      the actual role of TMS in the treatment of psychiatric conditions other than
      unipolar depression. 

PMID- 24112914
TI  - Pain.
AB  - Invasive stimulation of the motor (precentral) cortex using surgically implanted
      epidural electrodes is indicated for the treatment of neuropathic pain that is
      refractory to medical treatment. Controlled trials have demonstrated the efficacy
      of epidural motor cortex stimulation (MCS), but MCS outcome remains variable and
      validated criteria for selecting good candidates for implantation are lacking.
      Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach
      that could be used as a preoperative tool to predict MCS outcome and also could
      serve as a therapeutic procedure in itself to treat pain disorders. This requires
      repeated rTMS sessions and a maintenance protocol. Other studies have also
      demonstrated the efficacy of transcranial direct current stimulation (tDCS) in
      relieving chronic pain syndromes. The most studied target is the precentral
      cortex, but other targets, such as the prefrontal and parietal cortices, could be
      of interest. The analgesic effects of cortical stimulation relate to the
      activation of various circuits modulating neural activities in remote structures,
      such as the thalamus, limbic cortex, insula, or descending inhibitory controls.
      In addition to the treatment of refractory neuropathic pain by epidural MCS, new
      developments of this type of strategy are ongoing, for other types of pain
      syndrome and stimulation techniques. 

PMID- 24112915
TI  - Tinnitus: therapeutic use of superficial brain stimulation.
AB  - Tinnitus is a common disorder and traditional treatment approaches such as
      medication, active or passive sound enhancement, and cognitive behavioral therapy
      have limited efficacy. Thus, there is an urgent need for more effective treatment
      approaches. Functional imaging studies in patients with tinnitus have revealed
      alterations in neuronal activity of central auditory pathways, probably resulting
      as a consequence of sensory deafferentation. However, nonauditory brain areas are
      also involved. These nonauditory brain areas might represent both an "awareness"
      network involved in the conscious perception of the tinnitus signal as well as
      areas related to a nontinnitus-specific distress network consisting of the
      anterior cingulate cortex, anterior insula, and amygdala. Moreover, memory
      mechanisms involving the hippocampus and the parahippocampal region may play a
      role in the persistence of the awareness of the phantom percept, as well as in
      the reinforcement of the associated distress. All of these networks represent
      potential targets for treatment via pharmacological treatment or noninvasive and
      invasive brain stimulation. Repetitive transcranial magnetic stimulation (rTMS)
      is a noninvasive method of applying electromagnetic fields to the brain that can
      induce alterations of neuronal activity that outlast the stimulation period.
      Single sessions of rTMS over the temporal or temporoparietal cortex have been
      successful in transiently reducing tinnitus perception. Repeated sessions of rTMS
      have resulted in tinnitus relief in a subgroup of patients, lasting from several
      days to several months. However, effect sizes of rTMS in the treatment of
      tinnitus are only moderate, and interindividual variability is high. Larger and
      longer lasting effects have been observed with direct electrical stimulation of
      the auditory cortex via implanted epidural electrodes. Transcranial direct
      current stimulation (tDCS) has also shown potential for the treatment of
      tinnitus. Both auditory and frontal tDCS have shown tinnitus reduction in a
      subgroup of patients. In spite of the promising results of the different brain
      stimulation approaches, further research is needed before these techniques can be
      recommended for routine clinical use. 

PMID- 24112916
TI  - Parkinson's disease.
AB  - In advanced Parkinson's disease (PD), the emergence of symptoms refractory to
      conventional therapy poses therapeutic challenges. The success of deep brain
      stimulation (DBS) and advances in the understanding of the pathophysiology of PD
      have raised interest in noninvasive brain stimulation as an alternative
      therapeutic tool. The rationale for its use draws from the concept that reversing
      abnormalities in brain activity and physiology thought to cause the clinical
      deficits may restore normal functioning. Currently the best evidence in support
      of this concept comes from DBS, which improves motor deficits, and modulates
      brain activity and motor cortex physiology, although whether a causal interaction
      exists remains largely undetermined. Most trials of noninvasive brain stimulation
      in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting
      the motor cortex. Current studies suggest a possible therapeutic potential for
      rTMS and transcranial direct current stimulation (tDCS), but clinical effects so
      far have been small and negligible with regard to functional independence and
      quality of life. Approaches to potentiate the efficacy of rTMS include increasing
      stimulation intensity and novel stimulation parameters that derive their
      rationale from studies on brain physiology. These novel parameters are intended
      to simulate normal firing patterns or to act on the hypothesized role of
      oscillatory activity in the motor cortex and basal ganglia with regard to motor
      control and its contribution to the pathogenesis of motor disorders. Noninvasive
      brain stimulation studies will enhance our understanding of PD pathophysiology
      and might provide further evidence for potential therapeutic applications. 

PMID- 24112917
TI  - Dystonia.
AB  - Focal dystonias such as writer's cramp or blepharospasm are treatable with
      botulinum toxin injections and medications, but both therapies provide largely
      symptomatic relief. Because the basic abnormality in dystonia is at the synaptic
      level, brain modulating therapies with repetitive transcranial magnetic
      stimulation (rTMS) may well be able to produce lasting clinical improvement. Low
      frequency threshold or subthreshold rTMS over the premotor cortex or anterior
      cingulate cortex, for hand dystonia and blepharospasm, respectively, could in the
      future become a more curative treatment, perhaps in conjunction with the current
      therapies. 

PMID- 24112918
TI  - Epilepsy.
AB  - Noninvasive brain stimulation, particularly transcranial magnetic stimulation
      (TMS) and transcranial direct current stimulation (tDCS), are emerging as
      realistic tools for seizure control. Numerous open-label trials and a few recent
      randomized controlled trials suggest the capacity of both techniques to suppress
      seizures. Additionally, specialized TMS protocols aimed to map cortical function
      and to measure cortical excitability may have realistic roles as diagnostic tools
      in epilepsy. As the prevalence of drug-resistant epilepsy has not changed in
      recent years, TMS and tDCS offer noninvasive and nonpharmacological options to
      improve control of intractable seizures. 

PMID- 24112920
TI  - Plasticity.
AB  - A variety of noninvasive brain stimulation techniques have been used to study
      neuronal plasticity. Mostly, noninvasive techniques have been employed, and the
      bulk of studies have focused on the motor system, because its physiology is more
      readily accessible and physiological properties can be studied with greater
      detail than in other systems. In many of the protocols, general conclusions have
      been drawn from the motor potentials evoked by transcranial magnetic stimulation
      of the primary motor cortex. Several of the phenomena induced by noninvasive
      brain stimulation have been mapped on to cellular physiological mechanisms such
      as synaptic long-term potentiation or long-term depression. Although some
      parallelisms are intriguing, this approach has also its limitations, and more
      direct verification of physiological phenomena by animal studies is needed. 

PMID- 24112921
TI  - Parkinson's disease.
AB  - There have been a large number of basic research studies of noninvasive brain
      stimulation in Parkinson's disease. Initial work focused on measuring: (1) the
      excitability of corticospinal output with threshold and input-output measures,
      and (2) the effectiveness of intracortical gamma-aminobutyric acid (GABA)ergic
      inhibitory systems using short-interval intracortical inhibition (SICI), long
      interval intracortical inhibition (LICI), and silent period measures. Early
      suggestions of increased excitability and reduced inhibition have been
      progressively modified. There are conflicting reports on changes in excitability,
      silent period, and LICI, and the more consistent reduction in SICI is now viewed
      as a superimposed excitation rather than a primary deficit in a GABAergic
      mechanism. A small number of studies have suggested that premovement increases in
      corticospinal excitability may be prolonged in Parkinson's disease, consistent
      with the suggestion of slower buildup of the motor command to move; there are
      also modifications of interhemispheric connections in patients with mirror
      movements. Transcranial magnetic stimulation (TMS) has also been used to explore
      the involvement of motor cortex and cerebellum in resting and postural tremors by
      examining how readily they can be reset by single TMS pulses over each area. It
      can also probe the effects of deep brain stimulation of motor cortex
      excitability. Finally, new TMS techniques that examine synaptic plasticity in
      motor cortex have shown reduced excitability in patients off therapy which is
      restored when on therapy. Data are also emerging about the possible role of
      cortical plasticity in compensating for gradual loss of dopaminergic function
      prior to onset of clinical symptoms. 

PMID- 24112922
TI  - Transcranial magnetic stimulation in dystonia.
AB  - Transcranial magnetic stimulation (TMS) is a method of noninvasive brain
      stimulation that directly affects the cerebral cortex but not deep structures.
      TMS has been used extensively in patients with primary dystonia to test the
      excitability of connections within and among motor areas of the cortex, and has
      provided useful information on pathophysiology; however, interindividual
      variability in the responses has resulted in difficulties in translating this
      method into a clinically applicable diagnostic use. In addition, TMS studies have
      disclosed that dystonia is a disorder linked to a disruption of synaptic
      "scaling," with an excess of synaptic plasticity that is in keeping with findings
      obtained in animal models of dystonia. This alteration is a unique feature of
      organic dystonia and may be helpful in differentiating patients with psychogenic
      dystonia. Finally, TMS can potentially be used as a therapeutic tool to treat
      some forms of dystonia, such as focal hand dystonia, where pharmacological
      options or injections of botulinum toxin are often ineffective. 

PMID- 24112919
TI  - Noninvasive brain stimulation in neurorehabilitation.
AB  - Stroke is the major cause of long-term disability worldwide, with impaired manual
      dexterity being a common feature. In the past few years, noninvasive brain
      stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS)
      and transcranial direct current stimulation (tDCS), have been investigated as
      adjuvant strategies to neurorehabilitative interventions. These NIBS techniques
      can be used to modulate cortical excitability during and for several minutes
      after the end of the stimulation period. Depending on the stimulation parameters,
      cortical excitability can be reduced (inhibition) or enhanced (facilitation).
      Differential modulation of cortical excitability in the affected and unaffected
      hemisphere of patients with stroke may induce plastic changes within neural
      networks active during functional recovery. The aims of this chapter are to
      describe results from these proof-of-principle trials and discuss possible
      putative mechanisms underlying such effects. Neurophysiological and neuroimaging
      changes induced by application of NIBS are reviewed briefly. 

PMID- 24112923
TI  - Noninvasive brain stimulation in Huntington's disease.
AB  - Several important advances in the pathophysiology of Huntington's disease (HD)
      have been achieved by means of neurophysiological techniques designed to
      investigate the excitability and plasticity of brainstem and cortical circuits in
      patients with the condition. Studies designed to investigate brainstem reflexes,
      with paired-pulse and repetitive stimulation of the supraorbital nerve (blink
      reflex), have demonstrated abnormal excitability and plasticity of brainstem
      interneurons. In addition, several authors have tested the excitability of the
      primary motor cortex (M1) with the transcranial magnetic stimulation (TMS)
      technique and reported abnormal excitability of inhibitory intracortical circuits
      (cortical silent period, short afferent inhibition). Studies investigating
      plasticity processes by means of repetitive TMS (rTMS) protocols have
      demonstrated altered short-term as well as long-term M1 plasticity. Abnormal
      cortical excitability and plasticity can be present in the early phase of HD and
      in asymptomatic HD carriers. Evidence from a single study of small cohorts of
      patients with HD supports the therapeutic application of rTMS for symptomatic
      improvement of chorea in HD. 

PMID- 24112924
TI  - Utility of transcranial magnetic stimulation in delineating amyotrophic lateral
      sclerosis pathophysiology.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative
      disorder of the motor neurons in the motor cortex, brainstem, and spinal cord.
      The clinical phenotype of ALS is underscored by a combination of upper and lower
      motor neuron dysfunction. Although this phenotype was observed over 100 years
      ago, the site of ALS onset and the pathophysiological mechanisms underlying the
      development of motor neuron degeneration remain to be elucidated. Transcranial
      magnetic stimulation (TMS) enables noninvasive assessment of the functional
      integrity of the motor cortex and its corticomotoneuronal projections. To date,
      TMS studies have established cortical dysfunction in ALS, with cortical
      hyperexcitability being an early feature in sporadic forms of ALS and preceding
      the clinical onset of familial ALS. Taken together, a central origin of ALS is
      supported by TMS studies, with an anterograde dying-forward mechanism implicated
      in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish
      ALS from mimic disorders, despite a compatible peripheral disease burden, thereby
      suggesting a potential diagnostic utility of TMS in ALS. This chapter reviews the
      mechanisms underlying the generation of TMS parameters utilized in assessment of
      cortical excitability, the contribution of TMS in enhancing the understanding of
      ALS pathophysiology, and the potential diagnostic utility of TMS techniques in
      ALS. 

PMID- 24112925
TI  - Superficial brain stimulation in multiple sclerosis.
AB  - Central motor conduction time (CMCT) is the most frequently studied measure
      derived from transcranial magnetic stimulation (TMS) in multiple sclerosis (MS);
      it is abnormal in 57-93% of patients. Addition of the triple stimulation
      technique and combining motor with other evoked potentials (EPs) increases
      sensitivity. Cross-sectional correlations of TMS measures with clinical
      assessments of motor dysfunction or global disability are high. Longitudinally,
      CMCT is sensitive to both worsening and improvement of motor function, showing
      its potential to detect therapeutic responses. Moreover, combined multimodal EPs
      are valid quantitative predictors of the clinical course over periods ranging
      from 2 to 14 years. Measures of transcallosal connectivity (ipsilateral silent
      period and interhemispheric inhibition) are altered even in early MS, and yield
      complementary information on subclinical changes. Pathological brain plasticity
      in MS has been demonstrated by paired associative stimulation studies revealing a
      compensatory role of the ipsilateral motor and premotor areas. Central motor
      fatigue is associated with reduced motor EP amplitudes and increased cortical
      silent periods in normal controls, whereas patients with MS suffering from
      subjective fatigue show various abnormalities in cortical modulation of the motor
      system. 

PMID- 24112926
TI  - Brain stimulation in migraine.
AB  - Migraine is a very prevalent disease with great individual disability and
      socioeconomic burden. Despite intensive research effort in recent years, the
      etiopathogenesis of the disease remains to be elucidated. Recently, much
      importance has been given to mechanisms underlying the cortical excitability that
      has been suggested to be dysfunctional in migraine. In recent years, noninvasive
      brain stimulation techniques based on magnetic fields (transcranial magnetic
      stimulation, TMS) and on direct electrical currents (transcranial direct current
      stimulation, tDCS) have been shown to be safe and effective tools to explore the
      issue of cortical excitability, activation, and plasticity in migraine. Moreover,
      TMS, repetitive TMS (rTMS), and tDCS, thanks to their ability to interfere with
      and/or modulate cortical activity inducing plastic, persistent effects, have been
      also explored as potential therapeutic approaches, opening an interesting
      perspective for noninvasive neurostimulation for both symptomatic and preventive
      treatment of migraine and other types of headache. In this chapter we critically
      review evidence regarding the role of noninvasive brain stimulation in the
      pathophysiology and treatment of migraine, delineating the advantages and limits
      of these techniques together with potential development and future application. 

PMID- 24112927
TI  - Dementia.
AB  - Transcranial magnetic stimulation (TMS) has been used extensively to characterize
      motor system pathophysiology in Alzheimer's disease (AD) and other forms of
      dementia, as well to monitor the effects of certain pharmacological agents. Among
      the studies focusing on motor cortical excitability measures, the most consistent
      finding is a significant reduction of short-latency afferent inhibition (SAI) in
      AD and other forms of dementia in which the cholinergic system is affected, such
      as dementia with Lewy bodies. SAI evaluation may thus provide a reliable
      biomarker of cortical cholinergic dysfunction in dementias. Moreover, most TMS
      studies have demonstrated cortical hyperexcitability and asymptomatic motor
      cortex functional reorganization in the early stages of the disease. Integrated
      approaches utilizing TMS together with high-density EEG have indicated impaired
      cortical plasticity and functional connectivity across different neural networks
      in AD. Paired associative stimulation-induced plasticity has also been found to
      be abnormal in patients with AD. The development of novel noninvasive methods of
      brain stimulation, in particular repetitive TMS (rTMS) and transcranial direct
      current stimulation (tDCS), has increased the interest in neuromodulatory
      techniques as potential therapeutic tools for cognitive rehabilitation in AD.
      Preliminary studies have revealed that rTMS and tDCS can induce beneficial
      effects on specific cognitive functions in AD. Future studies are warranted to
      replicate and extend the initial findings. 

PMID- 24112928
TI  - Addiction.
AB  - Drug and alcohol addiction is a debilitating disorder characterized by persistent
      drug-seeking behaviors despite negative physiological, medical, or social
      consequences. Neurobiological models of addiction propose that the reinforcing
      effects of addictive drugs are associated with altered neurotransmission within
      the reward 'mesocorticolimbic' circuitry in the brain. Immense efforts are
      therefore designed to target the mesocorticolimbic circuitry in attenuating drug
      dependence and addiction-related behaviors. Yet, to date, most addiction
      treatments have demonstrated only limited success in reducing addiction-related
      behaviors. Accumulating and compelling evidence suggests that novel nonsurgical
      brain stimulation techniques, such as transcranial magnetic stimulation and
      transcranial direct current stimulation, could serve as promising tools for
      indexing altered neurotransmission associated with repetitive drug use, and
      moreover, may hold therapeutic potential for the treatment of drug dependence and
      addiction-related behaviors. This chapter reviews and discusses the current and
      potential applications of such techniques in the study and treatment of
      addiction; we focus on a number of common drugs of abuse, including nicotine,
      alcohol, cocaine, cannabis, and ecstasy. 

PMID- 24112929
TI  - Tourette syndrome.
AB  - This chapter addresses research applications of transcranial magnetic stimulation
      (TMS) in Tourette syndrome (TS). TS is a primary, idiopathic, neurological
      disorder characterized by multiple motor and vocal tics of childhood onset, with
      duration greater than 1 year, and associated in the majority of cases with
      attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder
      (OCD), and/or other psychiatric disorders. The majority of the chapter is a
      critical synopsis of case-control studies applying basic single- and paired-pulse
      TMS techniques to "resting" motor cortex. Newer applications of theta-burst
      stimulation are also analyzed. A number of intriguing findings have emerged,
      which may reflect abnormalities in several disrupted inhibitory or modulatory
      pathways that may underlie the tendency to manifest tics as well as commonly co
      occurring problems such as ADHD and OCD. Chapter sections are organized by type
      of TMS measurement, with each section describing briefly the technique, the
      pitfalls of the technique with regard to the above-described challenges, the
      findings in TS using that technique, and the possible implications for those
      findings in furthering our understanding of TS. Possible future applications for
      TMS in studying TS are also discussed. 

PMID- 24112930
TI  - Cerebellum.
AB  - The cerebellum plays an essential role in movement execution and motor control by
      modulating the primary motor cortex (M1) through cerebellothalamocortical
      connections. Transcranial electrical and magnetic stimulation (TMS) allows direct
      investigations of neural networks by stimulating neural structures noninvasively
      in humans. The motor evoked potential (MEP) to single-pulse TMS of M1 is used to
      measure the motor cortical excitability. A conditioning stimulus over the
      cerebellum preceding a test stimulus of the contralateral M1 enables us to study
      the cerebellar regulatory effects on M1. In this chapter we describe this
      cerebellar stimulation method and its usefulness as a diagnostic tool in clinical
      neurophysiology. 

PMID- 24112931
TI  - Transcranial magnetic stimulation and vision.
AB  - The challenge in visual neuroscience is to characterize the neuronal properties
      and functional significance of the numerous regions of the visual cortex, and to
      understand how they interact during the processing of visual information. The
      strength of transcranial magnetic stimulation (TMS) in this endeavor is its
      ability to assess the necessity of visual cortical areas in perceptual functions
      and to trace the corticocortical interactions that underlie them. Most of the
      early studies in this field were carried out using the so-called "virtual lesion"
      approach, in which the impact of TMS was thought to be akin to inducing a brain
      lesion in the stimulated area. This approach established causal links between
      specific visual areas and perceptual functions such as motion perception, object
      processing, and visual awareness. Recently, the view of TMS as a tool for
      inducing "virtual lesion" has been challenged by a number of experimental
      findings, giving rise to the conceptualization of TMS effects as a state
      dependent interaction between the initial state of the stimulated area and the
      parameters of the TMS pulse. This state dependency is the basis of paradigms
      aiming selectively to target specific neuronal representations and thus reveal
      neuronal tuning properties, a major challenge in the understanding of the
      cortical visual system. 

PMID- 24112932
TI  - Transcranial magnetic stimulation techniques to study the somatosensory system:
      research applications.
AB  - The introduction of brain stimulation research techniques such as transcranial
      magnetic stimulation (TMS) has greatly advanced the understanding of the
      somatosensory system in humans. Over the last several years, several studies have
      focused on applying TMS in a variety of contexts to alter transiently the
      excitability of the somatosensory cortex or regions that project to it and exert
      some control over its activity in specific behavioral contexts. Specific foci
      that are discussed in this chapter are methods of repetitive TMS, including theta
      burst protocols, delivered to the primary somatosensory cortex that have been
      shown to affect behavioral indices of somatic sensation such as tactile
      perception. Similar stimulation techniques can also be applied to distant areas
      that interact with and modulate activity in somatosensory cortex (i.e.,
      attentional or motor networks). For example, suppression of the dorsolateral
      prefrontal cortex modifies the attention-modulation of somatosensory information
      in modality-specific cortices. Overall this chapter is focused on understanding
      the interaction of activity in systems that function with the somatosensory
      system in behavioral contexts. These include systems such as those that control
      attention, whether sustained or selective between sensory modalities, or those
      that control movement based on targets present in other sensory systems. 

PMID- 24112933
TI  - Language.
AB  - Noninvasive focal brain stimulation by means of transcranial magnetic stimulation
      (TMS) has been used extensively in the past 20 years to investigate normal
      language functions. The picture emerging from this collection of empirical works
      is that of several independent modular functions mapped on left-lateralized
      temporofrontal circuits originating dorsally or ventrally to the auditory cortex.
      The identification of sounds as language (i.e., phonological transformations) is
      modulated by TMS applied over the posterior-superior temporal cortex and over the
      caudal inferior frontal gyrus/ventral premotor cortex complex. Conversely,
      attribution of semantics to words is modulated successfully by applying TMS to
      the rostral part of the inferior frontal gyrus. Speech production is typically
      interfered with by TMS applied to the left inferior frontal gyrus, onto the same
      cortical areas that also contain phonological representations. The cortical
      mapping of grammatical functions has been investigated with TMS mainly regarding
      the category of verbs, which seem to be represented in the left middle frontal
      gyrus. Most TMS studies have investigated the cortical processing of single words
      or sublexical elements. Conversely, complex elements of language such as syntax
      have not been investigated extensively, although a few studies have indicated a
      left temporal, frontal, and parietal system also involving the neocerebellar
      cortex. Finally, both the perception and production of nonlinguistic
      communicative properties of speech, such as prosody, have been mapped by TMS in
      the peri-Silvian region of the right hemisphere. 

PMID- 24112935
TI  - Transcranial stimulation and cognition.
AB  - Noninvasive brain stimulation (NIBS) is a unique method for studying cognitive
      function. For the study of cognition, NIBS has gained popularity as a
      complementary method to functional neuroimaging. By bypassing the correlative
      approaches of standard imaging techniques, it is possible to establish a putative
      relationship between brain cognition. In fact, functional neuroimaging data
      cannot demonstrate the actual role of a particular cortical activation in a
      specific function because an activated area may simply be correlated with task
      performance, rather than being responsible for it. NIBS can induce a temporary
      modification of performance only if the stimulated area is causally engaged in
      the task. In analogy with lesion studies, NIBS can provide information about
      where and when a particular process occurs. Based on this assumption, NIBS has
      been used in many different cognitive domains. However, one of the most
      interesting questions in neuroscience may not be where and when, but how
      cognitive activity occurs. Beyond localization approaches, NIBS can be employed
      to study brain mechanisms. NIBS techniques have the potential to influence
      behavior transiently by altering neuronal activity, which may have facilitatory
      or inhibitory behavioral effects. NIBS techniques include transcranial magnetic
      stimulation (TMS) and transcranial electrical stimulation (tES). TMS has been
      shown transiently to modulate neural excitability in a manner that is dependent
      mainly on the timing and frequency of stimulation (high versus low). The
      mechanism underlying tES is a change in neuronal membrane potentials that appears
      to be dependent mainly on the direction of current flow (anodal versus cathodal).
      Nevertheless, the final effects induced by TMS or tES depend on many technical
      parameters used during stimulation, such as the intensity of stimulation, coil
      orientation, site of the reference electrode, and time of application. Moreover,
      an important factor is the possible interactions between these factors and the
      physiological and cognitive state of the subject. To use NIBS in cognition, it is
      important to understand not only how NIBS functions but also the brain mechanisms
      being studied and the features of the area of interest. To describe better the
      advanced knowledge provided by NIBS in cognition, we will treat each NIBS
      technique separately and underline the related hypotheses beyond applications. 

PMID- 24112936
TI  - Preface. Discovery of electricity.

PMID- 24112937
TI  - Foreword. Scholarly contribution.

PMID- 24112938
TI  - Link up and fold up--templating the formation of spectrin tetramers.

PMID- 24112934
TI  - Learning and memory.
AB  - Learning and memory functions are crucial in the interaction of an individual
      with the environment and involve the interplay of large, distributed brain
      networks. Recent advances in technologies to explore neurobiological correlates
      of neuropsychological paradigms have increased our knowledge about human learning
      and memory. In this chapter we first review and define memory and learning
      processes from a neuropsychological perspective. Then we provide some
      illustrations of how noninvasive brain stimulation can play a major role in the
      investigation of memory functions, as it can be used to identify cause-effect
      relationships and chronometric properties of neural processes underlying
      cognitive steps. In clinical medicine, transcranial magnetic stimulation may be
      used as a diagnostic tool to understand memory and learning deficits in various
      patient populations. Furthermore, noninvasive brain stimulation is also being
      applied to enhance cognitive functions, offering exciting translational
      therapeutic opportunities in neurology and psychiatry. 

PMID- 24112939
TI  - Cooperative KaiA-KaiB-KaiC interactions affect KaiB/SasA competition in the
      circadian clock of cyanobacteria.
AB  - The circadian oscillator of cyanobacteria is composed of only three proteins,
      KaiA, KaiB, and KaiC. Together, they generate an autonomous ~24-h biochemical
      rhythm of phosphorylation of KaiC. KaiA stimulates KaiC phosphorylation by
      binding to the so-called A-loops of KaiC, whereas KaiB sequesters KaiA in a
      KaiABC complex far away from the A-loops, thereby inducing KaiC
      dephosphorylation. The switch from KaiC phosphorylation to dephosphorylation is
      initiated by the formation of the KaiB-KaiC complex, which occurs upon
      phosphorylation of the S431 residues of KaiC. We show here that formation of the
      KaiB-KaiC complex is promoted by KaiA, suggesting cooperativity in the initiation
      of the dephosphorylation complex. In the KaiA-KaiB interaction, one monomeric
      subunit of KaiB likely binds to one face of a KaiA dimer, leaving the other face
      unoccupied. We also show that the A-loops of KaiC exist in a dynamic equilibrium
      between KaiA-accessible exposed and KaiA-inaccessible buried positions.
      Phosphorylation at the S431 residues of KaiC shift the A-loops toward the buried
      position, thereby weakening the KaiA-KaiC interaction, which is expected to be an
      additional mechanism promoting formation of the KaiABC complex. We also show that
      KaiB and the clock-output protein SasA compete for overlapping binding sites,
      which include the B-loops on the CI ring of KaiC. KaiA strongly shifts the
      competition in KaiB's favor. Thus, in addition to stimulating KaiC
      phosphorylation, it is likely that KaiA plays roles in switching KaiC from
      phosphorylation to dephosphorylation, as well as regulating clock output. 

PMID- 24112940
TI  - The structure of Xis reveals the basis for filament formation and insight into
      DNA bending within a mycobacteriophage intasome.
AB  - The recombination directionality factor, Xis, is a DNA bending protein that
      determines the outcome of integrase-mediated site-specific recombination by
      redesign of higher-order protein-DNA architectures. Although the attachment site
      DNA of mycobacteriophage Pukovnik is likely to contain four sites for Xis
      binding, Xis crystals contain five subunits in the asymmetric unit, four of which
      align into a Xis filament and a fifth that is generated by an unusual domain
      swap. Extensive intersubunit contacts stabilize a bent filament-like arrangement
      with Xis monomers aligned head to tail. The structure implies a DNA bend of ~120
      degrees , which is in agreement with DNA bending measured in vitro. Formation of
      attR-containing intasomes requires only Int and Xis, distinguishing Pukovnik from
      lambda. Therefore, we conclude that, in Pukovnik, Xis-induced DNA bending is
      sufficient to promote intramolecular Int-mediated bridges during intasome
      formation. 

PMID- 24112941
TI  - Deciphering protein stability in cells.

PMID- 24112942
TI  - The molecular V brake.

PMID- 24112943
TI  - The effect of Porphyromonas gingivalis lipopolysaccharide on pregnancy in the
      rat.
AB  - OBJECTIVE: Periodontitis, mostly associated with Porphyromonas gingivalis, has
      frequently been related to adverse pregnancy outcomes. We therefore investigated
      whether lipopolysaccharides of P. gingivalis (Pg-LPS) induced pregnancy
      complications in the rat. METHODS: Experiment 1: pregnant rats (day 14) received
      increasing Pg-LPS doses (0.0-50.0 MUg kg(-1) bw; n = 2/3 p per dose). Maternal
      intra-aortic blood pressure, urinary albumin excretion, placental and foetal
      weight and foetal resorptions were documented. Experiment 2: 10.0 MUg kg(-1) bw
      (which induced the highest blood pressure together with decreased foetal weight
      in experiment 1) or saline was infused in pregnant and non-pregnant rats (n = 7/9
      p per group). Parameters of experiment 1 and numbers of peripheral leucocytes as
      well as signs of inflammation in the kidney and placenta were evaluated. RESULTS:
      Pg-LPS infusion in pregnant rats increased maternal systolic blood pressure,
      reduced placental weight (dose dependently) and decreased foetal weight and
      induced foetal resorptions. It, however, did not induce proteinuria or a
      generalised inflammatory response. No effects of Pg-LPS were seen in non-pregnant
      rats. CONCLUSION: Pg-LPS increased maternal blood pressure, induced placental and
      foetal growth restriction, and increased foetal resorptions, without inducing
      proteinuria and inflammation. Pg-LPS may therefore play a role in pregnancy
      complications induced by periodontitis.

PMID- 24112944
TI  - Long-term outcomes in patients with retinal vein occlusion treated with
      ranibizumab: the RETAIN study.
AB  - OBJECTIVE: To determine long-term outcomes of patients with ranibizumab-treated
      retinal vein occlusion (RVO). DESIGN: Prospective follow-up of a subset of
      patients from 2 phase 3 trials. PARTICIPANTS: Thirty-four patients with branch
      RVO (BRVO) and 32 with central RVO (CRVO) who completed the Genentech-sponsored
      ranibizumab study RVO trials. METHODS: Patients seen every month in year 1 and at
      least every 3 months in year 2 were treated with ranibizumab for intraretinal
      fluid. Patients requiring injections on consecutive visits were treated with
      ranibizumab plus scatter photocoagulation. MAIN OUTCOME MEASURES: Mean
      improvement in best-corrected visual acuity (BCVA) and percentage of patients
      with edema resolution. RESULTS: With a mean follow-up of 49.0 months, 17 of 34
      BRVO patients (50%) had edema resolution defined as no intraretinal fluid for 6
      months or more after the last injection. The last injection was given within 2
      years of treatment initiation in 76%. The mean number of injections required in
      unresolved patients in year 4 was 3.2. In patients with resolved edema mean
      improvement in BCVA was 25.9 letters versus 17.1 letters (P = 0.09) in unresolved
      patients, and in both groups, approximately 80% had a final BCVA of 20/40 or
      better. With a mean follow-up of 49.7 months, 14 of 32 CRVO patients (44%) had
      edema resolution, with 71% receiving their last injection within 2 years of
      treatment initiation. The mean number of injections in unresolved patients in
      year 4 was 5.9. Compared with patients with unresolved CRVO, patients with
      resolved disease had greater improvement in BCVA (25.2 vs. 4.3 letters; P =
      0.002), and a greater percentage had a final BCVA of 20/40 or better (64.3% vs.
      27.8%; P = 0.04). Nine patients with BRVO and 9 with CRVO received scatter
      photocoagulation, and with mean follow-up of 9 months (BRVO) and 11 months (CRVO)
      after last laser, only 1 in each group had resolution of edema. CONCLUSIONS: Long
      term outcomes in BRVO patients treated with ranibizumab were excellent, and
      although half still required occasional injections after 4 years, they maintained
      good visual potential. A substantial minority (44%) of patients with ranibizumab
      treated CRVO had edema resolution and a good outcome within 4 years, but most
      (56%) still required frequent injections, had reduced visual potential, and have
      a guarded prognosis.

PMID- 24112945
TI  - Assessing the effectiveness of surface cleaning methods in intravitreal injection
      procedure rooms.
AB  - PURPOSE: To assess cleaning effectiveness of room surfaces in an office-based
      intravitreal injection practice by using adenosine triphosphate (ATP)
      luminometry. DESIGN: Prospective, comparative case series. PARTICIPANTS: A total
      of 792 intravitreal injection room surfaces were sampled (396 before cleaning,
      396 after cleaning) using 3 cleaning methods. METHODS: Three cleaning methods
      were evaluated: baseline terminal cleaning, directed terminal cleaning, and
      enhanced terminal cleaning. For each method, residual ATP bioburden (relative
      light units [RLUs]/sample) was sampled from 9 high-touch injection room surfaces
      before and after terminal cleaning using the 3M Clean-Trace ATP System (3M Inc,
      St. Paul, MN). Surface ATP RLUs were used to compare cleaning methods and against
      an ATP benchmark of fewer than 250 RLU. Differences between cleaning methods were
      compared by using paired t tests with Bonferroni correction for 3 comparisons.
      MAIN OUTCOME MEASURES: Surface ATP RLU levels. RESULTS: In baseline terminal
      cleaning and directed terminal cleaning, the median ATP level of all surfaces
      exceeded threshold when sampled after terminal cleaning (391 RLU and 264 RLU,
      respectively), and levels were increased significantly at the completion of the
      injection clinic and before terminal cleaning (780 RLU and 626 RLU, respectively;
      P < 0.003). In enhanced terminal cleaning, the median ATP level was below
      threshold after terminal cleaning (71 RLU), was unchanged at the completion of
      injection clinic and before terminal cleaning (63 RLU; P = 0.27), and was
      significantly lower than after the baseline terminal and directed terminal
      cleaning methods (P < 0.003). CONCLUSIONS: An easily adopted enhanced terminal
      cleaning program reduced surface ATP bioburden in intravitreal injection rooms to
      less than clean benchmarks used in nonophthalmologic healthcare settings.

PMID- 24112946
TI  - Differential impairment of social cognition factors in bipolar disorder with and
      without psychotic features and schizophrenia.
AB  - While it is well-established that patients with schizophrenia and bipolar
      disorder exhibit deficits in social cognition, few studies have separately
      examined bipolar disorder with and without psychotic features. The current study
      addressed this gap by comparing patients with bipolar disorder with (BD+) and
      without (BD-) psychotic features, patients with schizophrenia (SZ), and healthy
      controls (NC) across social cognitive measures. Principal factor analysis on five
      social cognition tasks extracted a two-factor structure comprised of
      social/emotional processing and theory of mind. Factor scores were compared among
      the four groups. Results identified differential patterns of impairment between
      the BD+ and BD- group on the social/emotional processing factor while all
      clinical groups performed poorer than controls on the theory of mind factor. This
      provides evidence that a history of psychosis should be taken into account while
      evaluating social cognition in patients with bipolar disorder and also raises
      hypotheses about the relationship between social cognition and psychosis. 

PMID- 24112947
TI  - The beneficial effects of combining pharmacological and psychosocial treatment on
      remission and functional outcome in outpatients with schizophrenia.
AB  - OBJECTIVE: The effects of pharmacological and psychosocial treatment on remission
      and the functional outcome in outpatients with schizophrenia were evaluated.
      Remission was assessed according to the criteria proposed by the Remission in
      Schizophrenia Working group and psychosocial functioning according to the Global
      Assessment of Functioning with a score > 60. Functional outcome was the result of
      these two variables. METHOD: One hundred fifty two patients were randomized to
      receive either, antipsychotic treatment as usual (TAU) or social skills training
      and family psychoeducation in addition to TAU. A final sample of 119 patients: n
      = 68 in the social skills training group, and n = 51 in the TAU group completed
      the study protocol. Patients were assessed at baseline and at 6-month follow-up.
      RESULTS: At the end of the study, 80% of the patients fulfilled the criteria for
      symptomatic remission: 62 patients (91.2%) in the social skills training group in
      contrast to 34 patients (66.7%) in the TAU group. Functional improvement criteria
      were accomplished by 41 patients (34.5%) at the endpoint of the study. Forty of
      these patients (58.8%) belonged to social skills training and one patient to
      customary treatment (chi(2) = 41.7, df 1, p < 0.001) and when criteria for
      symptomatic remission and functional improvement were combined, 39 patients
      (97.5%) of the social skills training group and one patient (1.9%) of the
      customary treatment group achieved functional outcome. CONCLUSION: The results
      emphasize the need for psychosocial interventions as conjoint to pharmacological
      treatment to improve functional outcome in schizophrenia patients.

PMID- 24112948
TI  - Effectiveness and feasibility of early physical rehabilitation programs for
      geriatric hospitalized patients: a systematic review.
AB  - BACKGROUND: Old adults admitted to the hospital are at severe risk of functional
      loss during hospitalization. Early in-hospital physical rehabilitation programs
      appear to prevent functional loss in geriatric patients. The first aim of this
      review was to investigate the effect of early physical rehabilitation programs on
      physical functioning among geriatric patients acutely admitted to the hospital.
      The second aim was to evaluate the feasibility of early physical rehabilitation
      programs. METHODS: Two searches, one for physical functioning and one for
      feasibility, were conducted in PubMed, CINAHL, and EMBASE. Additional studies
      were identified through reference and citation tracking. To be included articles
      had to report on in-hospital early physical rehabilitation of patients aged 65
      years and older with an outcome measure of physical functioning. Studies were
      excluded when the treatment was performed on specialized units other than
      geriatric units. Randomized controlled trials were included to examine the effect
      of early physical rehabilitation on physical functioning, length of stay and
      discharge destination. To investigate feasibility also non randomized controlled
      trials were added. RESULTS: Fifteen articles, reporting on 13 studies, described
      the effect on physical functioning. The early physical rehabilitation programs
      were classified in multidisciplinary programs with an exercise component and
      usual care with an exercise component. Multidisciplinary programs focussed more
      on facilitating discharge home and independent ADL, whereas exercise programs
      aimed at improving functional outcomes. At time of discharge patients who had
      participated in a multidisciplinary program or exercise program improved more on
      physical functional tests and were less likely to be discharged to a nursing home
      compared to patients receiving only usual care. In addition, multidisciplinary
      programs reduced the length of hospital stay significantly. Follow-up
      interventions improved physical functioning after discharge. The feasibility
      search yielded four articles. The feasibility results showed that early physical
      rehabilitation for acutely hospitalized old adults was safe. Adherence rates
      differed between studies and the recruitment of patients was sometimes
      challenging. CONCLUSIONS: Early physical rehabilitation care for acutely
      hospitalized old adults leads to functional benefits and can be safely executed.
      Further research is needed to specifically quantify the physical component in
      early physical rehabilitation programs.

PMID- 24112949
TI  - Activation of heme oxygenase recovers motor function after spinal cord injury in
      rats.
AB  - Characterization of auto-destructive mechanisms, leading to cell death after
      spinal cord injury (SCI) is important to prevent further damage to tissue. Heme
      oxygenase (HO) catalyzes the oxidation of heme to biliverdin and carbon monoxide
      (CO), as a response to cell damage. Products of HO action have biological
      effects, as antioxidant biliverdin. We evaluated the changes of HO activity after
      injury, and the effect of pharmacological treatments with hemin (an inducer) and
      (Sn)-protoporphyrin (an inhibitor, Sn-PPIX) of HO, upon motor recovery after SCI.
      Female Wistar rats were submitted to SCI by trauma and sacrificed at several
      times (2, 4, 8, 12 and 24h) after injury to evaluate HO activity. Additional
      groups of rats were treated with either hemin or Sn-PPIX, to evaluate motor
      recovery, spared spinal cord tissue and HO activity. Results showed that HO
      control activity was increased by effect of SCI, at all times evaluated, as
      compared to sham group values. Twenty-four hours after injury, HO activity was
      increased 7.2-fold by hemin treatment, as compared to SCI plus vehicle group
      values. In addition, animals treated with hemin 2 and 8h after SCI, showed a
      better motor recovery and higher spared cord tissue, as compared to control group
      values. Our findings indicate that activation of HO is a beneficial mechanism
      when attained during the acute phase after SCI. 

PMID- 24112950
TI  - The Swedish version of the multidimensional scale of perceived social support
      (MSPSS)--a psychometric evaluation study in women with hirsutism and nursing
      students.
AB  - BACKGROUND: The Multidimensional Scale of Perceived Social Support (MSPSS) is a
      short instrument, developed to assess perceived social support. The original
      English version has been widely used. The original scale has demonstrated
      satisfactory psychometric properties in different settings, but no validated
      Swedish version has been available. The aim was therefore to translate, adapt and
      psychometrically evaluate the Multidimensional Scale of Perceived Social Support
      for use in a Swedish context. METHOD: In total 281 participants accepted to join
      the study, a main sample of 127 women with hirsutism and a reference sample of
      154 nursing students. The MSPSS was translated and culturally adapted according
      to the rigorous official process approved by WHO. The psychometric evaluation
      included item analysis, evaluation of factor structure, known-group validity,
      internal consistency and reproducibility. RESULTS: The original three-factor
      structure was reproduced in the main sample of women with hirsutism. An
      equivalent factor structure was demonstrated in a cross-validation, based on the
      reference sample of nursing students. Known-group validity was supported and
      internal consistency was good for all scales (alpha = 0.91-0.95). The test-retest
      showed acceptable to very good reproducibility for the items (kappaw = 0.58-0.85)
      and the scales (ICC = 0.89-0.92; CCC = 0.89-0.92). CONCLUSION: The Swedish
      version of the MSPSS is a multidimensional scale with sound psychometric
      properties in the present study sample. The simple and short format makes it a
      useful tool for measuring perceived social support.

PMID- 24112951
TI  - Safety and pharmacokinetics of a recombinant fusion protein linking coagulation
      factor VIIa with albumin in healthy volunteers.
AB  - BACKGROUND: Development of neutralizing antibodies remains the most problematic
      complication in treating congenital hemophilia. Control and prevention of
      bleeding events in such patients with recombinant factor VIIa (rFVIIa) is limited
      by the short half-life of the available product. Here, we report on the
      pharmacokinetics and safety of a novel, recombinant fusion protein linking
      coagulation FVIIa with albumin (rVIIa-FP) in a first-in-human study in healthy
      male subjects. METHODS: Forty healthy male subjects between 18 and 35 years of
      age were included and dosed in five consecutive cohorts. In each cohort, six
      subjects were randomized to a single dose of rVIIa-FP (140, 300, 500, 750, or
      1000 MUg kg(-1) ) and two to placebo. All subjects received anticoagulation with
      an oral vitamin K antagonist to reach an international normalized ratio between 2
      and 3 prior to dosing with rVIIa-FP/placebo. Dosing with oral vitamin K
      antagonist was continued at a fixed dose for 6 days after injection of rFVIIa.
      RESULTS AND CONCLUSIONS: Tolerance of rVIIa-FP was good at all dose levels. No
      serious adverse events were observed. None of the subjects developed anti-drug
      antibodies. The maximum baseline-corrected mean (SD) FVIIa plasma activity
      increased in a dose-proportional manner. Across the dose range, the median half
      life was consistent, ranging from 6.1 to 9.7 h. At the highest dose of 1000 MUg
      kg(-1) , the median FVIIa activity-based half-life was 8.5 h. Clearance ranged
      from 7.62 to 12.74 mL h(-1) kg(-1) . Compared with the commercially available
      rFVIIa product, rVIIa-FP had a reduced clearance resulting in an approximately 3-
      to 4-fold increase in half-life.

PMID- 24112952
TI  - Fibroblastic rheumatism: immunosuppressive therapy is not always required.
AB  - Fibroblastic rheumatism is a very rare cause of distal and bilateral
      polyarthritis characterized by cutaneous nodules, sclerodactylitis, thickened
      palmar fascia and Raynaud phenomenon. Physiopathology remains unknown and the
      diagnosis is histologic. Despite the use of immunosuppressive agents in some
      isolated cases with a variable efficacy, we report a case of typical fibroblastic
      rheumatism with severe digital retraction who dramatically improved after
      intensive physical therapy without immunosuppressive drugs prescription. Such a
      case illustrates that improvement may be spontaneous and that non pharmacological
      approach is a cornerstone in the management of this disease. 

PMID- 24112953
TI  - Fine structure of the urnulae of Balaustium mites (Actinotrichida: Erythraeidae)
      representing peculiar defense organs.
AB  - The urnulae, until now the enigmatic paired dorsal protrusions on idiosoma dorsum
      in active postlarval forms of Balaustium mites, were studied using electron
      microscopy. They consist of walls made of unmodified integument, which form a
      cylinder covered by a roof of thin cuticle. At the posterior border of the
      urnula, the roof has a crescent slit. On its inner surface, a rather large muscle
      inserts with several tendons. The roof forms a flap under which the modified
      columnar epidermal cells containing numerous lipid inclusions are located. These
      lipids are probably secreted through pore canals of the overlying cuticle.
      Materials mainly originating from an extensive vesicular tissue situated
      underneath the columnar cells of the urnula and under the adjacent unmodified
      epidermis are extruded through the mentioned slit. Our results support previous
      studies that have suggested a function of the urnulae as defensive organs. Our
      study further suggests that the agent that provides the repellent effect comes
      mainly from the vesicular tissue, whereas the columnar cells with their lipid
      secretions are likely to restore the external secretion layer of the epicuticle
      after its destruction during the repellent release. Further structural and
      functional details are discussed and compared with other putative defensive
      secretory organs. 

PMID- 24112954
TI  - Dependent heroin use and associated risky behaviour: the role of rash
      impulsiveness and reward sensitivity.
AB  - Impulsive temperament has long been considered as a risk factor for substance use
      disorders (SUD). Considering the heterogeneity of impulsivity, a biologically
      based 2-factor model incorporating reward sensitivity and rash impulsiveness
      facets, has been proposed. Here we report how these two facets of impulsiveness
      could be associated with different aspects of dependent heroin use and associated
      risky behaviour. Two hundred and ninety three dependent heroin users and 232 non
      users were assessed on reward sensitivity, rash impulsivity, and the related
      trait of punishment sensitivity. After adjusting for multiple comparisons, heroin
      users were found to be more rash-impulsive and reward-sensitive than non-users
      (p<0.001). Within users, rash impulsivity was associated with high risk behaviour
      including escalating heroin consumption, injecting heroin use, hazardous
      drinking, low treatment-seeking and risky sexual behaviour. Reward sensitivity
      was uniquely associated with early onset of drug use. While greater impulsivity
      is a common trait in drug users compared with non-users, the use of a 2-factor
      model of impulsivity provides additional information regarding specific aspects
      of drug initiation and maintenance that can be targeted in the prevention and
      treatment of heroin dependence. 

PMID- 24112955
TI  - N-Acetylcysteine affects obesity-related protein expression in 3T3-L1 adipocytes.
AB  - OBJECTIVES: Oxidative stress plays critical roles in the pathogeneses of
      diabetes, hypertension, and atherosclerosis, but its effect on fat accumulation
      is still unclear. In this study, we analyzed the role of the well-known
      antioxidant and a glutathione (GSH) precursor N-acetylcysteine (NAC) in fat
      accumulation and the expression of obesity-associated proteins. METHODS: We
      studied the effects of 10 uM NAC on obesity-related protein expression in
      cultured 3T3-L1 preadipocytes, which are able to differentiate into mature
      adipocytes and accumulate lipids. RESULTS: NAC treatment inhibited fat
      accumulation and reduced the expression of obesity-related proteins, including
      monoamine oxidase A, heat shock protein 70 (HSP70), aminoacylase -1 (ACY-1), and
      transketolase. DISCUSSION: Our results suggest that the effects of NAC on
      triglycerides (Tgs) and protein expression are correlated. In support of this, we
      showed that NAC treatment affected both the Tg synthesis pathway and the
      expression levels of proteins implicated in human obesity.

PMID- 24112956
TI  - Vitamin complex (ascorbic acid, alpha-tocopherol and beta-carotene) induces
      micronucleus formation in PBMNC unrelated to ROS production.
AB  - OBJECTIVES: To evaluate the correlation between reactive oxygen species (ROS)
      production and micronucleus formation induced by a vitamin complex in peripheral
      blood mononuclear cells from healthy people aged between 40 and 85 years old.
      METHODS: Peripheral blood mononuclear cells (PBMNCs) were purified utilizing
      ficoll-hypaque gradient. ROS production by PBMNCs was quantified by luminol
      dependent chemiluminescence in the presence or in the absence of the vitamin
      complex. DNA damage in PBMNC by the vitamin complex was detected by the
      micronucleus technique. Statistical analyses were made with the Student's 't'
      test and the Pearson correlation. P < 0.05 was considered significant. RESULTS:
      The vitamin complex induced MN formation in PBMNC but did not augment ROS
      production. There was no correlation between ROS production and MN formation
      either in the presence or in the absence of the vitamin complex. DISCUSSION:
      There was no increase in the ROS production in the presence of the vitamin
      complex. The vitamin complex induced an augmentation in the MN formation. There
      was no correlation between ROS production and the induction of MN formation.
      Since no association could be detected between ROS production and MN formation,
      additional studies are required in order to investigate the possible mechanism of
      vitamin-induced MN formation.

PMID- 24112957
TI  - Ameliorating effects of troxerutin on nickel-induced oxidative stress in rats.
AB  - OBJECTIVE: This study investigates the effects of troxerutin on nickel (Ni)
      induced oxidative stress in rats. METHODS: Nickel as nickel sulfate (20 mg/kg
      body weight (b.w.)) was administered intraperitoneally for 20 days to induce
      toxicity in the subject rats. The levels of stress markers AST, ALT, ALP, LDH,
      and GGT in the hepatic tissue were significantly increased while a decrease in
      the levels of enzymic and non-enzymic antioxidants was observed in Ni intoxicated
      rats. RESULTS: Oral administration of troxerutin along with Ni for 20 days in a
      dose-dependent manner significantly reverted the stress markers in the liver
      tissue to near normal level. Troxerutin exhibited significant protection at 100
      mg/kg b.w. Histopathological studies also supported the above findings.
      CONCLUSIONS: Thus, we conclude that troxerutin preserved the histo-architecture
      and ameliorated stress markers in the liver tissue of Ni-intoxicated rats.

PMID- 24112958
TI  - Nitric oxide concentrations in gas emanating from the tails of obese rats.
AB  - This study was undertaken to investigate the effects of oral L-arginine
      administration and exercising training on the NO concentration emanating from rat
      tail and NOx in plasma. Obese (fa/fa) Zucker rats (n = 22) were divided into four
      groups: (1) oral L-arginine administration (A) (n = 6), (2) exercise training
      (E), (3) exercise training + L-arginine administration (E + A) (n = 5), and (4)
      non-exercise training + non-L-arginine administration (N) (n = 6). The control
      (+/+) Zucker rats (n = 22) were also divided into the same four groups. The body
      weight of the E + A and the A groups was significantly lower than that of the N
      group. The NO concentration emitted from the tail was higher in the L-arginine (E
      + A and A) groups than in the non-L-arginine (E and N) groups in both obese and
      control rats. Exercise training did not affect the skin gas NO concentration in
      either obese or control rats. Plasma NOx concentrations in four obese rats were
      significantly higher than those observed in control rats. Exercise training did
      not influence the level of plasma NOx in obese or control rats. In conclusion,
      this study confirmed that L-arginine administration increases the skin gas NO
      concentration and obesity increases the plasma NOx level. The plasma NOx
      concentrations were not affected by L-arginine administration or exercise
      training in obese or control rats. 

PMID- 24112959
TI  - Tocotrienol prevents AAPH-induced neurite degeneration in neuro2a cells.
AB  - OBJECTIVES: Reactive oxygen species induce neurite degeneration before inducing
      cell death. However, the degenerative mechanisms have not yet been elucidated.
      While tocotrienols have a known neuroprotective function, the underlying
      mechanism remains unclear and may or may not involve antioxidant action. In this
      study, we hypothesize that free radical-derived membrane injury is one possible
      mechanism for inducing neurite degeneration. Therefore, we examined the potential
      neuroprotective effect of tocotrienols mediated through its antioxidant activity.
      METHODS: Mouse neuroblastoma neuro2a cells were used to examine the effect of the
      water-soluble free radical generator 2,2'-azobis(2-methylpropionamide)
      dihydrochloride (AAPH) on neurite dynamics. After 24 hours of AAPH treatment,
      cell viability, neurite number, and the number of altered neurites were measured
      in the presence or absence of alpha-tocotrienol. RESULTS: Treatment of neuro2a
      cells with a low concentration of AAPH induces neurite degeneration, but not cell
      death. Treatment with 5 uM alpha-tocotrienol significantly inhibited neurite
      degeneration in AAPH-treated neuro2a cells. Furthermore, morphological changes in
      AAPH-treated neuro2a cells were similar to those observed with colchicine
      treatment. CONCLUSIONS: alpha-Tocotrienol may scavenge AAPH-derived free radicals
      and alkoxyl radicals that are generated from AAPH-derived peroxyl radicals on
      cell membranes. Therefore, alpha-tocotrienol may have a neuroprotective effect
      mediated by its antioxidant activity.

PMID- 24112960
TI  - The Yin and Yang of redox regulation.
AB  - Mammalian cells produce reactive oxygen and nitrogen species (ROS/RNOS) in
      response to an oxidative environment. Powerful antioxidant mechanisms have been
      developed in order to avoid oxidative stress by contributing to the maintenance
      of redox homeostasis. Traditionally, accumulation of ROS/RNOS is considered
      deleterious for cells as it can lead to loss of cellular function, aging, and
      cell death. Consequently, ROS/RNOS imbalance has been implicated in the etiology
      and/or progression of numerous pathologies such as cardiovascular diseases,
      inflammation, and cancer. An interesting concept that has emerged more recently
      is that not only have cells developed efficient systems to cope with ROS/RNOS
      accumulation but they have also learned to profit of them under certain
      circumstances. This notion is supported by data showing that ROS/RNOS can act as
      signaling molecules affecting the function and activity of a multiplicity of
      protein kinases and phosphatases controlling cellular homeostasis. This review
      does not provide an exhaustive overview of molecular mechanisms linked to
      ROS/RNOS generation and processing but includes relevant examples highlighting
      the dichotomic nature of these small molecules and the multitude of effects
      elicited by their accumulation. This aspect of ROS/RNOS ought to be taken into
      account particularly in novel therapeutic setups that aim to achieve high
      efficiency and minimal or no side effects. 

PMID- 24112961
TI  - [Anaerobic bacteraemia in paediatric patients].

PMID- 24112962
TI  - A qualitative study of 'fear' as a regulator of children's independent physical
      activity in the suburbs.
AB  - A crisis discourse has developed within the health and physical activity
      literature that paints a disparaging picture about the decline of children's
      participation in active play and independent mobility. Fear as a moderator of
      children's mobility, in this case focused on independent active school travel
      (IAST), remains a poorly understood construct. Within the popular press and
      academic literature, middle class parents have been characterised as overly
      anxious towards culturally reinforced dangers whilst being ignorant of the
      benefits of IAST during childhood. Fear of strangers, dangers and risk-taking are
      portrayed as nebulous and irrational anxiety states that are contributing to
      another great fear, a fear that our children are getting fat. The study draws
      upon Tudor's, (2003), parameters of fear framework to explore parent negotiations
      of fear and risk associated with IAST. In depth individual and focus group
      interviews with parents (N=24) provide insight into meanings, rules and customs
      that govern the way in which fear is experienced and expressed within a middle
      class white suburb in Australia. Far from being irrational, and operating purely
      from drivers at a cultural level, parents were aware of the consequences of their
      decisions on a range of outcomes. Parents could articulate their own anxieties
      and in many cases the rational probabilities of anything bad happening. Fear was
      being constructed through complex relations, negotiated individually and
      collectively within a specific cultural and environmental context. In the process
      of their decision-making, there remained a constant negotiation between a desire
      to allow their child independence and the question 'what if?' Those seeking to
      mediate increased opportunities for children's IAST are encouraged to remove the
      rational/irrational focus that was redundant for parents in this study, and
      consider shifting the message toward the positive side of what is a highly
      contested decision making space for parents. 

PMID- 24112963
TI  - Socioeconomic inequalities in injury mortality in small areas of 15 European
      cities.
AB  - This study analysed socioeconomic inequalities in mortality due to injuries in
      small areas of 15 European cities, by sex, at the beginning of this century. A
      cross-sectional ecological study with units of analysis being small areas within
      15 European cities was conducted. Relative risks of injury mortality associated
      with the socioeconomic deprivation index were estimated using hierarchical
      Bayesian model. The number of small areas varies from 17 in Bratislava to 2666 in
      Turin. The median population per small area varies by city (e.g. Turin had 274
      inhabitants per area while Budapest had 76,970). Socioeconomic inequalities in
      all injury mortality are observed in the majority of cities and are more
      pronounced in men. In the cities of northern and western Europe, socioeconomic
      inequalities in injury mortality are found for most types of injuries. These
      inequalities are not significant in the majority of cities in southern Europe
      among women and in the majority of central eastern European cities for both
      sexes. The results confirm the existence of socioeconomic inequalities in injury
      related mortality and reveal variations in their magnitude between different
      European cities. 

PMID- 24112965
TI  - Attempts to reduce exposure to fungi, beta-glucan, bacteria, endotoxin and dust
      in vegetable greenhouses and a packaging unit.
AB  - Indoor handling of large amounts of plant materials occurs in different
      occupational settings including greenhouses and causes exposure to bioaerosols.
      The bioaerosol components fungi, beta-glucan, bacteria and endotoxin are involved
      in different airway symptoms and health effects can be dose-dependent. Therefore,
      there is a persistent need to reduce exposure. The aims of this study were to
      identify tasks causing exposure and to evaluate preventive measures aimed at
      reducing exposure of greenhouse workers to bioaerosols, and to study factors
      affecting the exposure. We have focused on different exposure scenarios; one with
      high short-term exposure found during clearing of old cucumber plants; the other
      with long-term, mid-level exposure found during tomato picking, leaf nipping,
      stringing up tomato plants, and packaging of cucumbers. Clearing of non-dried
      cucumber plants compared with clearing of dried cucumber plants significantly
      reduced the exposure to dust, endotoxin, bacteria, fungal spores and beta-glucan.
      More endotoxin and fungi are emitted and more of the emitted particles were of
      respirable size if the leaves were dried. Along the cucumber packaging line,
      exposure levels were highly specific to each personal subtask. The subtask
      'unloading of cucumbers' was the source of exposure making task ventilation or
      shielding of the process a possibility. Elimination of leaf debris on the floor
      reduced the exposure to fungi significantly. However, leaf debris on the floor
      did not contribute significantly to the exposure to dust, endotoxin and bacteria.
      Furthermore, to eliminate leaf debris, it had to be cleared away and this was
      associated with a higher exposure to dust and endotoxin. The age of the plants
      affected the exposure level to bioaerosols with higher exposures from old plants.
      In conclusion, different tasks and subtasks cause very different exposure levels.
      It is possible to reduce exposure by identifying subtasks causing the exposure
      and by modifying work processes, e.g., not drying out of plants. 

PMID- 24112966
TI  - Lead loading of urban roadways by motor vehicle wheel weights: some Australian
      observations using novel methodology.
AB  - Wheel weights fall off motor vehicles, accumulate on urban roadways and
      contribute to lead loading of the environment. The objective of the present
      research was to determine mass distribution, deposition rate, residence time,
      mass loss, and lead loading per annum on roadways in Melbourne, the capital city
      of Victoria, Australia. We surveyed wheel weights on 3-3.5 km segments of
      local/secondary roads over five years, and an 8.2 km segment of a primary
      arterial road over five month periods. The approach to steady state was also
      monitored using Global Positioning System (GPS) tracking of the position of
      weights deposited by motor vehicles. The average deposition rate and residence
      time were estimated using Poisson modeling of the observations. The distribution
      of wheel weight masses generally reflected the quantities supplied to the new car
      and tire market, with the 10 to 30 g range making up almost 70% of the total
      observed. The number of wheel weights observed was correlated with the commercial
      content of the route, but residence times depended on the location. The weighted
      average mass loss of wheel weights deposited on a primary arterial road was 5.9%
      and the average residence time was 38.1 days. Lead loading on Melbourne roadways
      was estimated to be 10.9 tonnes/year with 10.3 tonnes/year as intact pieces and
      0.6 tonne/year as particulates (or dissolved).

PMID- 24112967
TI  - A mathematical model of the initial interaction between Mycobacterium
      tuberculosis and macrophages.
AB  - There is a large body of literature describing molecular level interactions
      between Mycobacterium tuberculosis (Mtb) and macrophages. Macrophages initiate a
      range of anti-bacterial mechanisms in response to infection, and Mtb is capable
      of surviving and circumventing many of these responses. We apply a computational
      approach to ask: what are the effects on the cellular level of these opposing
      interactions? The model considers the interplay between bacterial killing and the
      pathogen's interference with macrophage function. The results reveal an
      oscillating balance between host and pathogen, but the balance is transient and
      varies in length, indicating that stochasticity in the bacterial population or
      host response could contribute to the diverse incubation periods observed in
      exposed individuals. The model captures host and strain variation and gives new
      insight into host-pathogen compatibility and co-evolution. 

PMID- 24112968
TI  - Leaf hydraulics I: scaling transport properties from single cells to tissues.
AB  - In leaf tissues, water may move through the symplast or apoplast as a liquid, or
      through the airspace as vapor, but the dominant path remains in dispute. This is
      due, in part, to a lack of models that describe these three pathways in terms of
      experimental variables. We show that, in plant water relations theory, the use of
      a hydraulic capacity in a manner analogous to a thermal capacity, though it
      ignores mechanical interactions between cells, is consistent with a special case
      of the more general continuum mechanical theory of linear poroelasticity. The
      resulting heat equation form affords a great deal of analytical simplicity at a
      minimal cost: we estimate an expected error of less than 12%, compared to the
      full set of equations governing linear poroelastic behavior. We next consider the
      case for local equilibrium between protoplasts, their cell walls, and adjacent
      air spaces during isothermal hydration transients to determine how accurately
      simple volume averaging of material properties (a 'composite' model) describes
      the hydraulic properties of leaf tissue. Based on typical hydraulic parameters
      for individual cells, we find that a composite description for tissues composed
      of thin walled cells with air spaces of similar size to the cells, as in
      photosynthetic tissues, is a reasonable preliminary assumption. We also expect
      isothermal transport in such cells to be dominated by the aquaporin-mediated cell
      to-cell path. In the non-isothermal case, information on the magnitude of the
      thermal gradients is required to assess the dominant phase of water transport,
      liquid or vapor. 

PMID- 24112969
TI  - Raynaud's phenomenon (primary).
AB  - INTRODUCTION: Raynaud's phenomenon is an episodic, reversible vasospasm of the
      peripheral arteries (usually digital). It causes pallor, followed by cyanosis
      and/or redness, often with pain and, at times, paraesthesia. On rare occasions,
      it can lead to ulceration of the fingers and toes (and, in some cases, of the
      ears or nose). This review focuses on primary (idiopathic) Raynaud's phenomenon,
      occurring in the absence of an underlying disease. The prevalence of primary
      Raynaud's phenomenon varies by sex, country, and exposure to workplace vibration.
      METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the
      following clinical question: What are the effects of drug treatments for primary
      Raynaud's phenomenon? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to August 2013 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 9 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review we present information relating to the effectiveness and safety
      of the following interventions: amlodipine, diltiazem, nicardipine, and
      nifedipine.

PMID- 24112970
TI  - Effects of smoking on outcomes after acute atherothrombotic stroke in Japanese
      men.
AB  - BACKGROUND: The effects of smoking on clinical outcomes following acute stroke
      remain controversial. METHODS: We evaluated the influence of smoking on 90-day
      outcomes after acute atherothrombotic stroke in 292 Japanese men extracted from
      the database of the Edaravone and Argatroban Stroke Therapy for Acute Ischemic
      Stroke randomized parallel-group trial that tested the safety and efficacy of
      edaravone and argatroban therapy in 814 patients in 2004-2008. Smokers were
      matched with non-smokers of the same age for identical age distribution in the
      smoker and non-smoker groups. Poor 90-day outcomes (defined as death, Barthel
      index<60, or modified Rankin score>3) were evaluated using a logistic regression
      model. Significant variables (P<0.05) in univariate analysis were further
      evaluated by multivariate logistic regression analysis using a forward-selection
      method. RESULTS: Body temperature, age, National Institute of Health Stroke Scale
      score at admission, systolic blood pressure, and smoking status were selected in
      the final model. Smokers had significantly increased odds of poor 90-day
      functional outcomes independent of other statistically significant predictor
      variables (adjusted odds ratio, 2.28; 95% confidence interval, 1.15-4.55;
      P=0.019). CONCLUSIONS: In Japanese men, smoking leads to poor functional outcomes
      at 3 months after acute atherothrombotic stroke.

PMID- 24112971
TI  - The impact of the receptor binding profiles of the vascular endothelial growth
      factors on their angiogenic features.
AB  - BACKGROUND: Vascular endothelial growth factors (VEGFs) are potential therapeutic
      agents for treatment of ischemic diseases. Their angiogenic effects are mainly
      mediated through VEGF receptor 2 (VEGFR2). METHODS: Receptor binding, signaling,
      and biological efficacy of several VEGFR2 ligands were compared to determine
      their characteristics regarding angiogenic activity and vascular permeability.
      RESULTS: Tested VEGFR2 ligands induced receptor tyrosine phosphorylation with
      different efficacy depending on their binding affinities. However, the tyrosine
      phosphorylation pattern and the activation of the major downstream signaling
      pathways were comparable. The maximal angiogenic effect stimulated by different
      VEGFR2 ligands was dependent on their ability to bind to co-receptor Neuropilin
      (Nrp), which was shown to form complexes with VEGFR2. The ability of these VEGFR2
      ligands to induce vascular permeability was dependent on their concentration and
      VEGFR2 affinity, but not on Nrp binding. CONCLUSIONS: VEGFR2 activation alone is
      sufficient for inducing endothelial cell proliferation, formation of tube-like
      structures and vascular permeability. The level of VEGFR2 activation is dependent
      on the binding properties of the ligand used. However, closely similar activation
      pattern of the receptor kinase domain is seen with all VEGFR2 ligands. Nrp
      binding strengthens the angiogenic potency without increasing vascular
      permeability. GENERAL SIGNIFICANCE: This study sheds light on how different
      structurally closely related VEGFR2 ligands bind to and signal via VEGFR2/Nrp
      complex to induce angiogenesis and vascular permeability. The knowledge of this
      study could be used for designing VEGFR2/Nrp ligands with improved therapeutic
      properties.

PMID- 24112972
TI  - The expanding roles of the Sd(a)/Cad carbohydrate antigen and its cognate
      glycosyltransferase B4GALNT2.
AB  - BACKGROUND: The histo-blood group antigens are carbohydrate structures present in
      tissues and body fluids, which contribute to the definition of the individual
      immunophenotype. One of these, the Sd(a) antigen, is expressed on the surface of
      erythrocytes and in secretions of the vast majority of the Caucasians and other
      ethnic groups. SCOPE OF REVIEW: We describe the multiple and unsuspected aspects
      of the biology of the Sd(a) antigen and its biosynthetic enzyme beta1,4-N
      acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and
      pathological settings. MAJOR CONCLUSIONS: The immunodominant sugar of the Sd(a)
      antigen is a beta1,4-linked N-acetylgalactosamine (GalNAc). Its cognate
      glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression,
      is regulated by unknown mechanisms - including promoter methylation, and encodes
      at least two different proteins, one of which with an unconventionally long
      cytoplasmic portion. In different settings, the Sd(a) antigen plays multiple and
      unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a
      potential role in the overexpression of sialyl Lewis antigens, increasing
      metastasis formation. 2) It is involved in the lytic function of murine cytotoxic
      T lymphocytes. 3) It prevents the development of muscular dystrophy in various
      dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates
      the circulating half-life of the von Willebrand factor (vWf), determining the
      onset of a bleeding disorder in a murine model. GENERAL SIGNIFICANCE: The
      expression of the Sd(a) antigen has a wide impact on the physiology and the
      pathology of different biological systems.

PMID- 24112973
TI  - Synthesizing and staining manganese oxide nanoparticles for cytotoxicity and
      cellular uptake investigation.
AB  - BACKGROUND: For decades, contrast agents have been used to reduce longitudinal
      (T1) or transverse (T2) relaxation times. High toxicity of gadolinium-based
      contrast agents leads researchers to new T1 contrast agents. Manganese oxide
      (MnO) nanoparticle (NP) with the lower peril and good enough signal change
      ability has been offered as a new possibility for magnetic resonance imaging
      (MRI). METHODS: The synthesized NPs were investigated for physicochemical and
      biological properties by X-ray diffraction, Fourier transform infrared
      spectroscopy, transmission electron microscope, dynamic light scattering (DLS),
      inductively coupled plasma, enzyme-linked immunosorbent assay, and 3T magnetic
      resonance imaging. RESULTS: Due to physical contact importance of T1 contrast
      agents with tissues' protons, extremely thin layer of the surfactant, less than
      2nm, was coated on NPs for aqueous stabilizing. The hydrophilic gentisic acid
      with low Dalton, around 154, did that role truly. Moreover, decreasing NP size to
      5nm which increases available surface for the proton relaxation is another
      important parameter to reach an appropriate longitudinal relaxation rate. The NPs
      didn't reveal any side effects on the cells, and cellular uptake was
      considerable. CONCLUSIONS: The synthesized NPs represented a promising result in
      comparison to clinical gadolinium chelates, due to higher r1 relaxivity and lower
      toxicity. GENERAL SIGNIFICANCE: In addition to considerable signal change and
      cellular uptake, Prussian blue was tried on MnO NPs for the initial time, which
      can be observed within cells by pale blue color.

PMID- 24112974
TI  - Spindle pole bodies.

PMID- 24112975
TI  - Anomalocaridids.

PMID- 24112976
TI  - Nematodes.

PMID- 24112977
TI  - Adaptation through horizontal gene transfer in the cryptoendolithic red alga
      Galdieria phlegrea.

PMID- 24112978
TI  - Contamination of beach sediments of a subalpine lake with microplastic particles.

PMID- 24112979
TI  - Eco-evolutionary dynamics: community consequences of (mal)adaptation.
AB  - Contemporary evolution can shape ecological dynamics at population, community and
      ecosystem levels. Innovative new experiments with walking sticks confirm this
      expectation by showing that adaptation to predatory birds has large effects on
      walking stick population sizes, arthropod communities and herbivory. 

PMID- 24112980
TI  - Cellular aging: symmetry evades senescence.
AB  - Cellular aging programs typically rely on the asymmetric shape and growth pattern
      of cells. A new study shows that symmetric fission yeast cells escape classic
      signs of aging until they encounter environmental stress. 

PMID- 24112981
TI  - Evolution: skipping school.
AB  - Some individual fish like to be close together in 'schools', while other
      individuals like to be alone. A pair of recent papers dissects the genetic basis
      of schooling behavior, showing that genetic changes in sensory systems are
      involved when this social behavior is lost during evolution.

PMID- 24112983
TI  - Animal evolution: trilobites on speed.
AB  - A new study quantifies rates of morphological and molecular evolution for
      arthropods during the critical Cambrian explosion. Both morphological and
      molecular evolution are accelerated--but not so much to break any speed limits.

PMID- 24112982
TI  - Chromosome segregation: not to put too fine a point (centromere) on it.
AB  - Localization of the histone H3 variant Cse4 (CENP-A) at the ~125 base pair point
      centromere in budding yeast directs assembly of a kinetochore that binds one
      microtubule. Recent work suggests there is more Cse4 at point centromeres than
      originally thought.

PMID- 24112984
TI  - Rapamycin resistance: mTORC1 substrates hold some of the answers.
AB  - The mechanism of action of the mTOR inhibitor rapamycin is poorly understood and
      why certain mTORC1 phosphorylation sites are rapamycin insensitive remains
      elusive. Site-specific analysis of mTORC1 substrates now suggests that the
      sequence composition of a phosphorylation site determines whether it is sensitive
      to rapamycin and starvation.

PMID- 24112985
TI  - Chromosome segregation: learning to let go.
AB  - To ensure accurate chromosome segregation, cohesion between sister chromatids
      must be released in a controlled manner during mitosis. A new study reveals how
      distinct centromere populations of the cohesin protector Sgo1 are regulated by
      microtubule attachments, cyclin-dependent kinases, and the kinetochore kinase
      Bub1. 

PMID- 24112986
TI  - Evolution: sperm, cryptic choice, and the origin of species.
AB  - In two fruit fly species, in vivo observations of competing sperm reveal how
      differences in sperm size, female behavior and reproductive architecture promote
      retention of same-species sperm. Sexual selection continues after mating and may
      play an important role in speciation.

PMID- 24112987
TI  - Mechanotransduction: the elusive hair cell transduction channel revealed?
AB  - A family of transmembrane proteins has been shown to modulate both the calcium
      permeability and single-channel conductance of the vertebrate hair-cell
      mechanosensor, implicating them directly in inner ear mechanosensation.

PMID- 24112989
TI  - Bone marrow edema induced by a bullet after a self-inflicted accidental firing.
AB  - We present a case of a postmortem finding of bone marrow edema in postmortem
      magnetic resonance imaging (PMMR) indirectly induced by a bullet, which barely
      missed the bone of a 92-year-old man found kneeling in front of his bed of a tidy
      apartment. Additionally, a selective postmortem computed tomography angiography
      (PMCTA) of the left leg was performed, visualizing a laceration of the left
      femoral vein by the bullet with consecutive contrast media extravasation. A vast
      pulmonary fat embolism was diagnosed and together with the blood loss found to be
      the cause of death.

PMID- 24112988
TI  - Dynamin assembly strategies and adaptor proteins in mitochondrial fission.
AB  - Mitochondrial fission is mediated by a dynamin-related GTPase that assembles at
      constricted sites on the organelle. The mechanism of action of this GTPase in
      fission is related to that of classical dynamin, which severs the necks of
      clathrin-coated pits at the plasma membrane. The scale of these membrane
      remodeling events differs by an order of magnitude, however, and structural
      studies have revealed variations in the assembly properties of classical and
      mitochondrial dynamins that accommodate these differences. Despite this progress,
      structural and mechanistic models have not yet incorporated a growing number of
      adaptor proteins that are required for the membrane recruitment and function of
      mitochondrial dynamins. Here, we review the structure and assembly properties of
      the yeast and mammalian mitochondrial dynamins and discuss what is known about
      the activities of their adaptor proteins. 

PMID- 24112990
TI  - An autopsy case of otogenic intracranial abscess and meningitis with Bezold's
      abscess: evaluation of inflammatory bone destruction by postmortem cone-beam CT.
AB  - The deceased was an unidentified young male found unconscious on a walkway. On
      autopsy, outer and inner fistulae of the left temporal bone, subcutaneous abscess
      in the left side of the neck and head, and an intracranial abscess were noted. A
      portion of the left temporal bone was removed and scanned by cone-beam computed
      tomography (CT) (normally used for dentistry applications) to evaluate the
      lesion. The cone-beam CT image revealed roughening of the bone wall and
      hypolucency of the mastoid air cells, consistent with an inflammatory bone
      lesion. According to autopsy and imaging findings, the cause of death was
      diagnosed as intracranial abscess with Bezold's abscess secondary to left
      mastoiditis as a complication of otitis media. Although determining the
      histopathology of bone specimens is time-consuming and costly work, we believe
      that use of cone-beam CT for hard tissue specimens can be useful in forensic
      practice. 

PMID- 24112991
TI  - Allele frequencies of 37 short tandem repeat loci in a Japanese population.
AB  - Allele frequencies for 37 STR autosomal loci (D1S1656, D2S1338, D2S1360, D2S441,
      D3S1358, D3S1744, D4S2366, D5S2500, D5S818, D6S474, D7S1517, D7S820, D8S1132,
      D8S1179, D10S1248, D10S2325, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11,
      D21S2055, D22S1045, CSF1PO, F13A01, F13B, FESFPS, FGA, LPL, Penta C, Penta D,
      Penta E, SE33, TH01, TPOX, vWA) were obtained from a sample of 175 unrelated
      individuals in a Japanese population. 

PMID- 24112992
TI  - Neutrality of miniSTR D22S1045 marker by Ewing's sarcoma phenotype.
AB  - Neutrality investigations of markers with forensic use are important to see if a
      phenotypic trait is being expressed in relation to the alleles of the marker.
      MiniSTR marker D22S1045 (locus 22q12.3) is localized near the breakpoint region
      of the EWS gene (22q12.2), which leads to the development of Ewing's Sarcoma.
      Analyzing allele frequencies and linkage disequilibrium in Ewing's sarcoma
      patients and non-affected populations, we found that the marker mD22S1045 was
      neutral when related to Ewing's Sarcoma. 

PMID- 24112993
TI  - [Myasthenia, from the internist's point of view].
AB  - Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a
      neuromuscular transmission defect causing muscle fatigability. If onset of the
      disease may be at any age, myasthenia gravis concerns mostly young adults, in
      majority females. The disease characteristic features are the following: ocular
      symptoms (ptosis or diplopia) as main initial manifestation, extension to other
      muscles in 80 % of the cases, variability of the deficit, effort induced
      worsening, successive periods of exacerbation during the disease course, severity
      depending on respiratory and swallowing impairment (if rapid worsening, a
      myasthenic crisis is to be suspected), association with thymoma in 20 % of
      patients and with other various autoimmune diseases, most commonly
      hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical
      features, improvement with cholinesterase inhibitors, detection of specific
      autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by
      electrophysiological tests. The points concerning specifically the internist have
      been highlighted in this article: diagnostic traps, associated autoimmune
      diseases, including inflammatory myopathies that may mimic myasthenia gravis,
      adverse effects of medications commonly used in internal medicine, some of them
      inducing myasthenic syndromes. The treatment is well codified: the treatment is
      well codified: (1) respect of adverse drugs contra-indications, systematically
      use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with
      radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in
      severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or
      intravenous immunoglobulins for patients with myasthenic crisis.

PMID- 24112994
TI  - Less and less-influence of volume on hand coverage and bactericidal efficacy in
      hand disinfection.
AB  - BACKGROUND: Some manufacturers recommend using 1.1 mL per application of alcohol
      based handrubs for effective hand disinfection. However, whether this volume is
      sufficient to cover both hands, as recommended by the World Health Organization,
      and fulfills current efficacy standards is unknown. This study aimed to determine
      hand coverage for three handrubs (two gels based on 70% v/v and 85% w/w ethanol
      and a foam based on 70% v/v ethanol) applied at various volumes. METHODS:
      Products were tested at product volumes of 1.1 mL, 2 mL, 2.4 mL as well as 1 and
      2 pump dispenser pushes; the foam product was tested in addition at foam volumes
      of 1.1 mL, 2 mL, and 2.4 mL. Products were supplemented with a fluorescent dye
      and 15 participants applied products using responsible application techniques
      without any specific steps but the aim of completely covering both hands.
      Coverage quality was determined under ultraviolet light by two blinded
      investigators. Efficacy of the three handrubs was determined according to ASTM E
      1174-06 and ASTM E 2755-10. For each experiment, the hands of 12 participants
      were contaminated with Serratia marcescens and the products applied as
      recommended (1.1 mL for 70% v/v ethanol products; 2 mL for the 85% w/w ethanol
      product). Log10-reduction was calculated. RESULTS: Volumes < 2 mL yielded high
      rates of incomplete coverage (67%-87%) whereas volumes >= 2 mL gave lower rates
      (13%-53%). Differences in coverage were significant between the five volumes
      tested for all handrubs (p < 0.001; two-way ANOVA) but not between the three
      handrubs themselves (p = 0.796). Application of 1.1 mL of 70% v/v ethanol rubs
      reduced contamination by 1.85 log10 or 1.60 log10 (ASTM E 1174-06); this failed
      the US FDA efficacy requirement of at least 2 log10. Application of 2 mL of the
      85% w/w ethanol rub reduced contamination by 2.06 log10 (ASTM E 1174-06),
      fulfilling the US FDA efficacy requirement. Similar results were obtained
      according to ASTM E 2755-10. CONCLUSIONS: Our data indicated that handrubs based
      on 70% ethanol (v/v) with a recommended volume of 1.1 mL per application do not
      ensure complete coverage of both hands and do not achieve current ASTM efficacy
      standards.

PMID- 24112995
TI  - A meta-analysis: neoadjuvant chemotherapy versus primary surgery in ovarian
      carcinoma FIGO stageIII and IV.
AB  - BACKGROUND: The purpose of the current study is to analyze the existing data
      comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in
      patients with advanced ovarian carcinoma. METHODS: Patients with stage IIIC and
      IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane
      Library, and EMBASE database (1989 to February 2013). Two authors independently
      extracted the data. To assess the risk of bias of included literatures, Cochrane
      Collaboration's risk of bias tool was used. Meta-analysis on literatures was
      conducted by using RevMan 5.2 software. RESULTS: Two high-quality randomized
      controlled trials (RCTs) met the inclusion criteria. These multicenter trials
      randomized 1,220 women with stage IIIc/IV ovarian cancer to NACT or PDS followed
      by chemotherapy. There were no significant differences between the study groups
      with regard to overall survival (OS) (1,120 women; HR 0.98; 95% CI 0.85 to 1.14)
      or progression-free survival (PFS) (1,120 women; HR 1.03; 95% CI 0.91 to 1.16).
      CONCLUSION: There was no statistical difference in median OS and PFS between the
      two treatment groups. With regard to selecting who will benefit from NACT,
      treatment should be tailored to the patient and should take into account
      respectability, age, histology, stage, and performance status.

PMID- 24112996
TI  - Early intersubjective skills and the understanding of intentionality in young
      children with Down syndrome.
AB  - This study examined the relationship between early intersubjective skills (joint
      attention and affect sharing) and the development of the understanding of
      intentionality in 16 young children with Down syndrome (DS) and 16
      developmentally matched children with other developmental disabilities (DD). The
      study of intentionality focuses on how children come to understand the goal
      directed actions of others and is an important precursor to the development of
      more complex social cognitive skills, such as theory of mind. Joint attention and
      affect sharing were examined using the Early Social Communication Scales (Mundy,
      Sigman, & Kasari, 1990; Seibert, Hogan, & Mundy, 1982). Meltzoff's (1995)
      behavioral reenactment paradigm was used to examine the understanding of
      intentionality. For children with DS, higher rates of affect sharing were
      associated with poorer intention reading abilities. This pattern was not observed
      in children with other DD. These results suggest that the intersubjective
      strengths associated with DS may not support the development of intentionality
      interpretation skills. Future research is needed to explore if children with DS
      have the joint attention behaviors needed to be intentional. 

PMID- 24112997
TI  - Association between maternal iron supplementation during pregnancy and risk of
      celiac disease in children.
AB  - BACKGROUND & AIMS: The aim of our study was to determine whether the use of iron
      supplements during pregnancy affects the risk for celiac disease in children.
      METHODS: We assessed data from the prospective Norwegian Mother and Child cohort
      study, in which individuals with celiac disease were identified by answers on
      questionnaires and linkage to the Norwegian Patient Register. Complete data were
      available for 78,846 children (mean age 5.9 years, range 2-12 years); 314
      children were identified with celiac disease. Questionnaires were given to
      pregnant women to collect information on use of iron-containing supplements,
      diet, anemia, and levels of hemoglobin. RESULTS: Celiac disease was diagnosed in
      4.65 of 1000 children whose mothers took iron supplements while they were
      pregnant, compared with 3.15 of 1000 children whose mothers did not. After
      adjusting for children's age, sex, and age of gluten introduction, and the
      presence of celiac disease in mothers, iron supplementation during pregnancy
      remained significantly associated with celiac disease in children (odds ratio
      [OR], 1.33; 95% confidence interval [CI], 1.05-1.68; P = .019). However, celiac
      disease was not associated with the mothers' intake of iron from foods (adjusted
      OR, 1.00; 95% CI, 0.97-1.03). Anemia before or during the early stages of
      pregnancy was not significantly associated with the risk of celiac disease in
      children (adjusted OR, 1.24; 95% CI, 0.84-2.00; P = .24). The use of iron
      supplements during pregnancy remained significantly associated with celiac
      disease in children after adjusting for children who were given iron supplements
      before 18 months of age, which itself was associated with celiac disease.
      CONCLUSIONS: In a prospective Norwegian Mother and Child cohort study, we found
      an increased risk of celiac disease in children whose mothers used iron
      supplements during pregnancy; this association does not appear to arise from
      maternal anemia.

PMID- 24112998
TI  - Body mass index and liver stiffness affect accuracy of ultrasonography in
      detecting steatosis in patients with chronic hepatitis C virus genotype 1
      infection.
AB  - BACKGROUND & AIMS: Few studies have evaluated the accuracy of ultrasonography in
      detecting steatosis in patients with chronic hepatitis C. We assessed its
      accuracy in detecting steatosis and factors that affect its diagnostic
      performance in consecutive patients with chronic hepatitis C virus genotype 1
      infection. METHODS: We analyzed data from 515 patients with chronic hepatitis C,
      confirmed by liver biopsy, assessing anthropometric, biochemical, metabolic,
      virologic, and ultrasonography features. Transient elastography was performed to
      measure liver stiffness. Steatosis was identified with ultrasonography based on
      detection of a bright liver echo pattern. RESULTS: Ultrasonography identified
      steatosis in 5% or more of parenchyma of the liver with 63.6% sensitivity, 90.4%
      specificity, an 87.5% positive predictive value (PPV), and a 70.3% negative
      predictive value (NPV). The higher the degree of steatosis (based on histology
      analysis), the higher the sensitivity values and NPVs (up to values of 75.3% and
      93.8%, respectively, for steatosis in >=30% of liver), and the lower the
      specificity values and PPVs (down to values of 69.8% and 31.7% for steatosis in
      >=30% of liver, respectively). Body mass index of 30 kg/m(2) or greater (odds
      ratio, 2.761; 95% confidence interval, 1.156-6.595; P = .02) and liver stiffness
      measurements of 8.9 kPa or higher (odds ratio, 3.128; 95% confidence interval,
      1.715-5.706; P < .001) were independent risk factors for false-negative results
      from ultrasonography when there was 5% or more steatosis, as well as when there
      was 10% or more, 20% or more, or 30% or more steatosis. CONCLUSIONS:
      Ultrasonography detects steatosis with low levels of accuracy in patients with
      chronic hepatitis C virus genotype 1 infection; it has low NPVs for amounts of
      steatosis of 5% or more and low PPVs for livers with moderate-severe amounts.
      Higher body mass indexes and liver stiffness measurements are associated with
      false-negative results in steatosis detection by ultrasonography.

PMID- 24112999
TI  - Neurophysiologic effects of repeated exposure to antidepressant medication: are
      brain functional changes during antidepressant administration influenced by
      learning processes?
AB  - Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that
      many individuals require multiple courses of antidepressant medication treatment.
      While some patients respond completely to each course of treatment, many do not,
      and with each unsuccessful antidepressant trial the likelihood that a patient
      will respond decreases. This raises the possibility that neurophysiologic
      response in subsequent antidepressant treatment may be influenced by learning
      processes including sensitization, habituation, and/or classical conditioning.
      Classical conditioning would entail the association of cues such as pill-taking
      (conditioned stimuli; CS) with the effects of active medication (unconditioned
      stimulus; US), such that later presentation of the CS alone would come to elicit
      a conditioned response (CR). Such effects could be revealed by blinded
      administration of placebo following a period of treatment with active medication.
      Habituation effects (tolerance), or sensitization effects (increased response),
      which require only repeated exposure to a stimulus, might be evidenced after
      repeated courses of antidepressant treatment. Knowledge of how learning processes
      impact neurophysiologic response to successive courses of antidepressant
      treatment would have relevance for clinical populations. Specific hypotheses,
      however, may be tested in healthy non-clinical samples to avoid potential
      confounding factors related to severity or chronicity of illness. Learning
      theories would suggest two hypotheses: (1) neurophysiologic response to placebo
      will differ between subjects who were previously treated with antidepressant
      treatment as compared to placebo (classical conditioning hypothesis); and (2)
      neurophysiologic response to an initial course of antidepressant treatment will
      differ from response to a repeated course of antidepressant treatment. Pilot data
      addressed these hypotheses in healthy never-depressed women who had previously
      received four weeks of venlafaxine IR, 150 mg (antidepressant-experienced
      subjects; n=2) or matching placebo (antidepressant-naive subjects; n=4) under
      double-blind conditions. Six-and-a-half years later, we treated these six women
      with placebo for one week, followed by four weeks of double-blind treatment with
      venlafaxine IR, 150 mg. Brain functional changes over the course of treatment
      were assessed using quantitative electroencephalography (qEEG) to compare
      prefrontal neurophysiologic responses between subjects who had, versus had not,
      previously been exposed to venlafaxine. Antidepressant-experienced versus
      antidepressant-naive subjects showed greater decreases in prefrontal cordance
      (PFC) during venlafaxine administration (sensitization hypothesis) but did not
      show significantly different PFC changes during treatment with placebo in this
      small pilot sample (classical conditioning hypothesis). Data suggest that brief
      treatment with antidepressant medication may have an enduring impact on
      neurophysiologic responses to a subsequent course of antidepressant treatment.
      Hypotheses should be tested in larger samples.

PMID- 24113000
TI  - Phylogenetic analysis and molecular characteristics of 17 porcine reproductive
      and respiratory syndrome virus isolates in Southern China from 2010 to 2011.
AB  - We analyzed the complete genomic sequences of 17 porcine reproductive and
      respiratory syndrome virus (PRRSV) isolates from Southern China obtained between
      2010 and 2011 and found that four of seven isolates from 2011 were closely
      related to the JXA1-R strain (vaccine virus of JXA1). This close relationship
      between field isolates and China domestic vaccine viruses has not been reported
      to date. The occurrence of vaccine-like viruses potentially creates a threat for
      the pig breeding industry and brings difficulties for control of this disease. 

PMID- 24113001
TI  - [Treatment choice after EGFR-TKI resistance].

PMID- 24113002
TI  - [Progressive patterns of gifitinib treating advanced non-small cell lung cancer
      after obtained resistance].
AB  - BACKGROUND AND OBJECTIVE: Clinical observation was conducted on the resistance to
      epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib
      (Iressa) therapy for advanced non-small cell lung cancer (NSCLC) patients.
      METHODS: Ninety-three NSCLC patients in our hospital, showing effective or stable
      condition after 6-month previous gefitinib therapy, were included in this
      investigation. Among the patients, 94.6% of them were suffering from
      adenocarcinoma. The percentage of female is 79.6%; the percentage of non-smoking
      is 80.6%. During the therapy period, follow-up was preformed every 2 months.
      RESULTS: Among the 93 patients, median therapy time was 16 months (range: 8 to 70
      months), and 21.5% (20/93) of them had received therapy for more than 2 years,
      while 8.6% (8/93) had received that for more than 3 years. The progression
      included 80% (72/90) for intrapleural progression, 38.9% (35/90) for primary
      tumor plus recurrence after sugary especially, 51.1% (46/90) for intrapulmonary
      metastasis, 25.6% (23/90) for pleural metastasis, 30% (30/90) for intracranial
      progression and 15.6% (14/90) for intraperitoneal progression. CONCLUSION:
      Resistance to EGFR-TKI shows diversification in clinical observation, therefore,
      close clinical follow-up is necessary for early attention and timely treatment.

PMID- 24113003
TI  - [Local treatment combined with EGFR-TKIs for advanced non-small cell lung cancer
      with solitary progression during EGFR-TKI treatment].
AB  - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) are routine treatments for non-small cell lung cancer
      (NSCLC) with EGFR mutation. Different clinical modes can be used to treat
      patients with TKI resistance, one of which is solitary progression. The aim of
      this study is to analyze available treatments for patients undergoing solitary
      progression. METHODS: Clinical data of 45 patients with advanced NSCLC who
      received local radiotherapy combined with EGFR-TKI after solitary progression
      were reviewed and analyzed. RESULTS: Among the 45 patients, 11 showed partial
      response, 23 achieved stable disease state, and 11 experienced progressive
      disease. The median of progression-free survival (PFS) was 5.9 months.
      CONCLUSION: Local therapies combined with EGFR-TKIs can prolong the PFS of
      patients with NSCLC who exhibited solitary progression during EGFR-TKI treatment.

PMID- 24113004
TI  - [Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced
      non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Advanced non-small cell lung cancer (NSCLC) is a common
      malignancy that is incurable. No standard treatment exists for recurrent
      patients. This article analyzed the efficacy and safety of sunitinib (37.5 mg qd)
      on a continuous daily dosing (CDD) schedule in treating recurrent advanced NSCLC.
      METHODS: We retrospectively analyzed the short-term efficacy and toxicity of
      sunitinib CDD in treating 17 patients who had previously undergone multiple
      cycles of therapy for advanced NSCLC in our hospital from January 2011 to
      December 2012. Treatment-related survival was also analyzed. RESULTS: Among the
      17 patients, the best overall response was partial response in 1 patient (5.9%),
      stable disease in 7 patients (41.2%), and progressive disease in 9 patients
      (52.9%). The overall response rate was 5.9%, and the disease control rate was
      47.1%. The median progression-free survival was 4.4 months (95%CI: 4.05-7.46).
      The main grade 3/4 toxicity was hand-foot skin reaction. CONCLUSION: Sunitinib
      (37.5 mg QD) CDD enabled good objective response in advanced NSCLC patients who
      had previously received multiple cycles of treatment and was well tolerated.

PMID- 24113005
TI  - [Treatment choice for advanced non-small cell lung cancer patients who had
      gradual progression after EGFR-TKIs: 32 cases report].
AB  - BACKGROUND AND OBJECTIVE: The epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) have been widely used in the treatment of the advanced non
      small cell lung cancer (NSCLC), especially in the adenocarcinoma patients with
      activating EGFR mutations. But there is no published overview of the following
      treatment. This report through observing the efficacy, toxicity and overall
      survival of different treatments to the advanced NSCLC patients who had gradual
      progression after EGFR-TKIs, evaluates the influence of the continued treatment
      and switching chemotherapy. METHODS: Retrospective review is conducted on 32
      cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs.
      One group accepted the continued treatment and the other group accepted the
      switching chemotherapy. RESULTS: The median overall survival of the continued
      treatment group is 36.0 months. The respose rate of the switching chemotherapy
      group is 43.75%, and clinical benefit rate (complete and partial response and
      stable disease) is 87.5%. The median overall survival is 15.5 months. The main
      toxicities are nausea, vomiting and hematological toxicities. CONCLUSION: For the
      advanced NSCLC patients who had gradual progression after EGFR-TKIs, the
      continued treatment is one of the acceptable choices.

PMID- 24113006
TI  - [Efficacy of chemotherapy after EGFR-TKIs resistance in 191 patients with Unknow
      EGFR gene mutation in advanced lung adenocarcinoma].
AB  - BACKGROUND AND OBJECTIVE: Subsequent chemotherapy were needed in patients with
      advanced pulmonary adenocarcinoma experiencing disease progression after
      epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)
      treatment. The study is to explore factors potentially influencing efficacy of
      subsequent chemotherapy. METHODS: One hundred and ninety-one patients with
      advanced lung adenocarcinoma, who were resistant from EGFR-TKIs and then received
      subsequent chemotherapy, were identified. Data of patient's characteristics,
      responses to chemotherapy and survival time were analyzed retrospectively.
      RESULTS: The overall response rate of the pemetrexed-based chemotherapy (9.3%)
      was higher than non-pemetrexed-based regimen (1.1%), P=0.011. Furthermore, the
      response in the second-line was more obvisous [objective response rate (ORR)
      14.3% vs 3.7%, P=0.041]. The patients who achieved response of partial response
      (PR) showed longer progression-free survival (PFS) than those who achieved non-PR
      (PFS 10.1 months and 2.3 months, P=0.012). The patients treated with platinum
      based chemotherapy had longer PFS and OS than those with non-platinum-based
      chemotherapy, therefore platinum-based regimen was independent prognosis factors
      for PFS and OS (PFS: RR=0.634, 95%CI: 0.466-0.832, P=0.004; OS: RR=0.666, 95%CI:
      0.460-0.960, P=0.030), especially the pateients who were aquired EGFR-TKIs
      resistance and who got drmatic progression from EGFR-TKIs treatment might got
      more benefits from platinum-based chemotherapy. However there was no significant
      difference in ORR, PFS or OS between patients with TKIs primary resistance and
      acquired resistance, or between dramtic progression and gradual/local
      progression. CONCLUSION: The patients with advanced lung adenocarcinoma might get
      benefits from pemetrexed-based or platinum-based chemotherapy after they were
      EGFR-TKIs resistace.

PMID- 24113007
TI  - [Research progress of the resistance mechanism of non-small cell lung cancer to
      EGFR-TKIs].
AB  - Nowadays, lung cancer is the malignant tumor of the highest morbidity and
      mortality over the world, and non-small cell lung cancer (NSCLC) makes up about
      80%. There is a great many NSCLC patients have been in advanced stage when
      diagnosed. As a result, people pay more attention to curing advanced NSCLC. The
      standard treatment to advanced NSCLC is platinum-based combined chemotherapy.
      However, chemotherapy drugs usually have limited effects on improving the
      survival of the patients. Then exploring new therapies is extremely urgent to us.
      Now, molecular targeted therapy has been the most promising research area for the
      treatment of NSCLC with researches going deep into pathogenesis and biological
      behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase
      inhibitors (EGFR-TKIs) have achieved a great success in the treatment of advanced
      NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been
      widely used to treat advanced NSCLCs worldwide, especially for the patients with
      EGFR activating mutations. However, after a period of treatment (median time is 6
      to 12 months), most patients will develop drug resistance to EGFR-TKIs. Intense
      research in these NSCLCs has identified two major mechanisms of resistance to
      TKIs: primary and acquired resistances. The research about resistance mechanism
      of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on
      improving overall and progression-free survival. The aim of this article was to
      summarize the development of the resistance mechanisms. 

PMID- 24113008
TI  - [Expression of PEPT2 mRNA in lung tissue of rats with pulmonary fibrosis].
AB  - BACKGROUND AND OBJECTIVE: Pulmonary fibrosis is a common pathological phenomenon
      in lung cancer patients after chemotherapy or radiotherapy. It is also a key
      hindrance to the transport of drugs to lung tissue. Peptide transporters have
      become a target of the rational design of peptides and peptide drugs. The aim of
      this study is to investigates the expression of peptide transporter 2 (PEPT2)
      mRNA in the lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis.
      METHODS: Fifty healthy adult Sprague-Dawley rats were randomly divided into five
      groups. One group was untreated (control), the second group was injected with
      normal saline solution (NS), and the three remaining groups were treated with a
      single dose of bleomycin to induce pulmonary fibrosis (BLM). Rats from the NS
      group were killed by exsanguination on day 14. Rats from the BLM group were
      killed by exsanguination on days 7, 14, and 28. The lung samples were observed
      under light microscopy and the hydroxyproline concentration was determined. The
      expression levels of PEPT2 mRNA were measured by RT-PCR. RESULTS: The
      morphological study showed that collagenous fiber proliferated in the lungs of
      rats injected with BLM, indicating pulmonary fibrosis. This proliferation was
      apparent at 14 d post-injection and especially at 28 d post-injection.
      Hydroxyproline levels increased seven days post-injection compared with the
      control group and NS group, but there was no significant statistical difference
      (P>0.05). Hydroxyproline levels significantly increased (P<0.05) 14 d and 28 d
      post-infection. The change in the lung tissue pathology coincided with the change
      in hydroxyproline levels. There were no significant changes of pulmonary PEPT2
      mRNA expression levels among the different groups (P>0.05). CONCLUSION: PEPT2 is
      a potential peptide drug target in the treatment of pulmonary fibrosis, although
      there were no significant changes of PEPT2 mRNA expression in the lungs of rats
      with bleomycin-induced pulmonary fibrosis.

PMID- 24113009
TI  - [Correlation between expression of TUBB3/STMN1 and EGFR signaling pathway in non
      small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that biomarkers play a key role in
      the individualized treatment of lung cancer. Correlations between expressions of
      TUBB3/STMN1 and gene mutations of epidermal growth factor receptor (EGFR),
      Kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral
      oncogene homolog B (BRAF), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)
      in non-small cell lung cancer (NSCLC) would be investigated and this may provide
      essential significance on prognosis and predictions of drug efficiency. METHODS:
      This study total enrolled 46 NSCLC patients. Tumor specimens were resected. The
      gene expressions of TUBB3, STMN1 were analyzed using branched DNA-liquidchip, and
      EGFR, KRAS, BRAF, PI3K gene mutations were detected by xTAG-liquidchip.
      Correlations between gene expressions and gene mutations were further analyzed by
      Spearman. RESULTS: Co-expressions between TUBB3 and STMN1 are strongly
      demonstrated, and high expression of TUBB3 always exists as well as high
      expression of STMN1 (P=0.006). Meanwhile mutation of EGFR E21 is negatively
      correlated with TUBB3, and wild type of EGFR E21 always exists toghther with high
      expression of TUBB3 (P=0.004,6), whereas mutation of KRAS E2 is positively
      associated with expression level of STMN1 (P=0.038,6). CONCLUSION:
      Antimicrotubule drug resistance factors of TUBB3 and STMN1 may be related with
      mutations of EGFR signal pathway, suggesting that EGFR mutation and KRAS mutation
      may be important factors in regulation of TUBB3/STMN1 expression, which provided
      basic references for chemotherapeutic resistance.

PMID- 24113010
TI  - [Advance of lung cancer screening with low-dose spiral CT].
AB  - Lung cancer has become the leading cause of cancer mortality globally, and 5-year
      survival rate is very poor. Screening and early detection are vital to improve
      survival and decrease mortality of lung cancer. In recent 20 years, low-dose
      spiral CT (LDCT) screening has become a research focus in this area. Randomized
      controlled trials have confirmed that LDCT can decrease lung cancer mortality.
      However, there are still some problems of LDCT. In this paper, we summarized the
      controversy that whether low-dose helical CT screening can reduce lung cancer
      mortality or not before its effectiveness was been confirmed, the results and
      problems in the randomized controlled trials and gave a prospect of low-dose
      helical CT screening's future application. 

PMID- 24113011
TI  - [Research status on targeted therapy for squamous cell lung cancer].
AB  - With the research of driver mutations, targeted therapy for lung cancer has made
      a great progress. Compared with lung adenocarcinoma, treatment of squamous cell
      lung cancer (SCC) has been far behind. While targeted therapies have improved
      outcomes for patients with lung adenocarcinoma, such as EGFR-TKIs, EML4-ALK
      inhibitors, molecularly targeted drugs are poorly active for SCC. SCC currently
      lacks therapeutically exploitable genetic alterations. These observations
      emphasize the need for new driver mutations and "druggable" targets in SCC
      patients. Combining with the research in recent years, this review will discuss
      the research status in targeted therapy for SCC. 

PMID- 24113012
TI  - [A case report of primary mediastinal seminoma diagnosised as pulmonary
      fibrosis].

PMID- 24113013
TI  - Synthesis, spectroscopic and DFT studies of novel fluorescent dyes: 3
      aminoimidazo[1,2-a]pyridines possessing 4-pyrone moieties.
AB  - A series of novel imidazo[1,2-a]pyridines possessing 4-pyrone ring were
      synthesized by three-component condensation of 4-pyrone carbaldehydes, 2
      aminopyridines and isocyanides. Bismuth (III) chloride was used as a catalyst in
      these reactions and desired products were synthesized in good yields at a very
      short period of time under solvent free conditions. UV-Vis absorption and
      fluorescence emission spectra of these compounds were investigated. It shown that
      two of these compounds (10f and 10g) exhibit intense fluorescence in
      dichloromethane. Optimized ground-state molecular geometries and orbital
      distributions of these two fluorescent dyes were obtained using density
      functional theory (DFT). Thermogravimetric analysis and electrochemical
      properties of these compounds were also studied.

PMID- 24113014
TI  - Structural, optical and morphological analyses of pristine titanium di-oxide
      nanoparticles--synthesized via sol-gel route.
AB  - Pure titanium di-oxide nanoparticles (TiO2) were synthesized by sol-gel technique
      at room temperature with appropriate reactants. The synthesis of anatase phase
      TiO2 nanoparticles was achieved by tetraisopropyl orthotitanate and 2-propanol as
      common starting materials and the product was annealed at 450  degrees C for 4 h.
      The synthesized product was characterized by X-ray diffraction analysis (XRD),
      Fourier transform infrared spectroscopy (FTIR), UV-VIS-Diffuse reflectance
      spectroscopy (DRS), Photoluminescence (PL) spectroscopy and Scanning electron
      microscopy (SEM) with Energy dispersive X-ray (EDX) analysis. XRD pattern
      confirmed the crystalline nature and tetragonal structure of synthesized
      composition. Average grain size was determined from X-ray line broadening, using
      the Debye-Scherrer relation. The functional groups present in the sample were
      identified by FTIR spectroscopy. Diffuse reflectance measurement indicated an
      absorption band edge on UV-region. The allowed direct and indirect band gap
      energies, as well as the crystallite size of pure TiO2 nanoparticles are
      calculated from DRS analysis. The microstructure and elemental identification
      were done by SEM with EDX analysis.

PMID- 24113015
TI  - Static and dynamic model fluorescence quenching of laser dye by carbon
      tetrachloride in binary mixtures.
AB  - The fluorescence quenching of laser dye namely 4,4(''')-Bis (2-butyloctyl-oxy)-p
      quaterphenyl [BIBUQ] by carbon tetrachloride has been studied in different
      solvent mixtures of 1-4 dioxane (DN) and acetonitrile (AN) at room temperature.
      The quenching is found to be appreciable and a positive deviation from linearity
      was observed in the Stern-Volmer plot in all the solvent mixtures. Various
      parameters for the quenching process have been determined by sphere of action
      static quenching model and finite sink approximation model. The magnitudes of
      these rate parameters indicate that positive deviation in the Stern-Volmer (S-V)
      plot is both due to static and dynamic processes. 

PMID- 24113016
TI  - Spectroscopic characterization of charge transfer complexes of 2,3
      diaminopyridine with chloranilic acid and dihydroxy-p-benzoquinone in polar
      solvent.
AB  - Charge transfer (CT) complexes formed between 2,3-aminopyridine (2,3-DAP) as
      electron donor with the pi-electron acceptors chloranilic acid (CHA) and
      dihydroxy-p-benzoquinone (DHBQ) were investigated spectrophotometrically in
      ethanol. Minimum-maximum absorbance method has been used for estimating the
      formation constants of the charge transfer reactions (KCT). Job's method of
      continuous variation and photometric titration studies were used to detect the
      stoichiometric ratios of the formed complexes and they showed that 1:1 complexes
      were produced. The molar extinction coefficient (epsilon), oscillator strength
      (f), dipole moment (MU), charge transfer energy (ECT), ionization potential (IP)
      and the dissociation energy (W) of the formed complexes were estimated, they
      reached acceptable values suggesting the stability of the formed CT-complexes.
      The solid CT-complexes were synthesized and characterized by elemental analyses,
      (1)H NMR and FTIR spectroscopies where the formed complexes included proton and
      electron transfer. 

PMID- 24113017
TI  - Electrical stimulation of somatic afferent nerves in the foot increases bladder
      capacity in healthy human subjects.
AB  - PURPOSE: We determined whether electrical stimulation of somatic afferent nerves
      in the foot could delay bladder filling sensations and increase bladder capacity
      in healthy humans without overactive bladder. MATERIALS AND METHODS: Eight
      subjects underwent 90-minute foot stimulation using skin surface electrodes
      connected to a transcutaneous electrical nerve stimulator. The electrodes were
      attached to the bottom of the foot. Subjects completed a 3-day voiding diary,
      during which foot stimulation was applied on day 2. Stimulation parameters were
      pulse frequency 5 Hz, rectangular waveform pulse width 0.2 milliseconds and
      intensity 2 to 6 times the minimal stimulation current necessary to induce toe
      twitch. Stimulation intensity was set by each subject to a maximal level without
      causing discomfort. Subjects were provided with 500 to 1,000 ml of water to drink
      during stimulation. RESULTS: Average +/- SE volume per void was 350 +/- 22 ml
      during the 24 hours before foot stimulation. This voided volume increased to a
      mean of 547 +/- 52 ml for up to 5 hours after stimulation (p <0.01). Average
      voided volume returned to 363 +/- 21 ml within 36 hours after stimulation. There
      were no adverse events. CONCLUSIONS: Foot stimulation can delay bladder filling
      sensations and significantly increase bladder capacity in healthy humans without
      overactive bladder. Although the study group was small, our results support
      moving forward with clinical trials of foot neuromodulation in patients with
      overactive bladder.

PMID- 24113019
TI  - Clinical indications and results after chest wall resection for recurrent
      mesothelioma.
AB  - OBJECTIVE: The ipsilateral hemithorax is the most common site of recurrence after
      surgical resection for malignant pleural mesothelioma. Salvage treatment has
      generally been ineffective. We reviewed the outcomes after resection of isolated
      ipsilateral chest recurrence after cytoreductive surgery in patients with
      malignant pleural mesothelioma. METHODS: Patients with malignant pleural
      mesothelioma who underwent initial surgical resection at our institution from
      1988 to 2011 and were subsequently treated for localized recurrence with an
      additional chest resection were identified and their data retrospectively
      reviewed. RESULTS: A total of 1142 patients underwent either extrapleural
      pneumonectomy (n = 794) or pleurectomy/decortication (n = 348). Of the patients
      who returned for follow-up, 47 (4.1%) had chest wall recurrence amenable to
      resection. The location of recurrence was predominantly incisional (49%) and/or
      costophrenic (38%). The median time to recurrence after either extrapleural
      pneumonectomy or pleurectomy/decortication was 16.1 months (range, 2.7-58.2). No
      30-day mortality was found for chest wall resection, and the median length of
      stay in the hospital was 3 days (range, 0-12). The median overall survival
      duration after chest wall resection correlated positively with the time to
      recurrence (epithelial: median, 8.9, 17.2, and 35.8 months for a time to
      recurrence of <12, 12 to <24, and >=24 months, respectively; biphasic: median,
      2.7 and 15.9 months for a time to recurrence of <10 and >=10 months,
      respectively). CONCLUSIONS: Chest wall resection is a safe and effective
      therapeutic option in the management of localized chest wall recurrence of
      malignant pleural mesothelioma. The time to recurrence appears to be predictive
      of the expected survival benefit in both epithelial and biphasic malignant
      pleural mesothelioma.

PMID- 24113020
TI  - Salvage periaortic pericardial baffle equalizes mortality in bleeding patients
      undergoing aortic surgery.
AB  - OBJECTIVE: Bleeding is a potentially serious complication of aortic surgery. We
      report our experience with the use of a periaortic bovine pericardial baffle to
      control intractable intraoperative bleeding. METHODS: All patients who underwent
      aortic root, ascending, or arch replacements between January 2002 and April 2013
      were reviewed. A bovine pericardial periaortic baffle was created to shunt shed
      blood into the right atrium. The transverse sinus was sutured closed in patients
      undergoing primary sternotomy. Baffle recipients were compared with the remaining
      patients undergoing aortic surgery. The Fisher exact test was used to determine
      statistical significance for categoric variables. Continuous variables were
      compared using the nonparametric Wilcoxon rank-sum test. All factors with a P
      value less than .2 were considered for multivariate logistic regression to
      determine independent associations with baffle use. RESULTS: A total of 413
      patients were identified, of whom 23 received a baffle. Operative mortality for
      patients receiving a baffle was 4% (1/23) compared with 6% (25/390) (P = 1) for
      the remaining patients. Prolonged ventilation was more common in the baffle
      recipients (P < .0005); otherwise, there were no differences in postoperative
      morbidity. Multivariate analysis of all patients undergoing aortic surgery
      revealed infectious endocarditis (P < .0005; odds ratio, 15.1; 95% confidence
      interval, 4.8-47.2), redo sternotomy (P < .0005; odds ratio, 11.9; 95% confidence
      interval, 4.1-34.1), and male gender (P = .04; odds ratio, 4.6; 95% confidence
      interval, 1.1-19.3) to be predictive of baffle placement. CONCLUSIONS: Patients
      requiring salvage periaortic pericardial baffle for intractable intraoperative
      hemorrhage experienced an operative mortality similar to that in the remaining
      patients undergoing aortic surgery. Infectious endocarditis requiring root
      replacement or reoperative aortic surgery should alert the surgeon to the
      potential need for baffle placement, including prophylactic transverse sinus
      closure.

PMID- 24113021
TI  - Historical perspectives of The American Association for Thoracic Surgery: Frank
      S. Dolley (1884-1961).

PMID- 24113022
TI  - Hemodynamic outcomes of geometric ring annuloplasty for aortic valve repair: a 4
      center pilot trial.
AB  - OBJECTIVES: A geometric annuloplasty ring could improve efficacy and stability of
      aortic valve repair. Toward this goal, a 1-piece 3-dimensional titanium
      annuloplasty ring with Dacron covering was developed and tested successfully in
      animals. The purpose of this study was to define hemodynamic outcomes with this
      device used as the annuloplasty component of human aortic valve repair. METHODS:
      In a 4-center pilot trial with informed consent, 16 patients underwent aortic
      valve repair for aortic insufficiency, with the annuloplasty device sutured into
      the annulus beneath the leaflets. Preoperative annular diameter averaged 26.5 +/-
      2.0 (mean +/- standard deviation) mm, and average ring size was 22.3 +/- 1.2 mm.
      After annuloplasty, leaflet defects were easy to identify, and 14 of 16 patients
      (88%) required leaflet plication and/or autologous pericardial reconstruction for
      leaflet defects. Three patients had ascending aortic replacement, and 2 had
      remodeling root replacement. One had ultrasonic leaflet decalcification and
      another tricuspid valve annuloplasty. Follow-up data were from site-specific
      studies at the 6-month postoperative time point. RESULTS: There were no in
      hospital mortalities or major complications. Preoperative aortic insufficiency
      grade (0-4 scale) was 3.6 +/- 1.0 and fell to 1.0 +/- 0.8 at 6 months (P <
      .0001). New York Heart Association class fell from 2.5 +/- 0.5 to 1.1 +/- 0.3 (P
      < .0001). Postrepair valve area was 2.7 +/- 0.2 cm(2), and 6-month mean systolic
      gradient was 11.3 +/- 3.3 mm Hg. Left ventricular end-diastolic diameter and
      ejection fraction both normalized (both P < .0001). CONCLUSIONS: Geometric ring
      annuloplasty facilitated aortic valve repair, allowing more precise
      reconstruction of leaflet defects. Aortic insufficiency reduction and systolic
      gradients were excellent, and expansion of valve reconstruction into broader
      categories of aortic valve disease seems indicated.

PMID- 24113023
TI  - Surgical site infections and bloodstream infections in infants after cardiac
      surgery.
AB  - OBJECTIVE: Few recent studies have assessed the epidemiology of and risk factors
      for surgical site infections (SSIs) and bloodstream infections (BSIs) in infants
      after cardiac surgery. We hypothesized that infants younger than 30 days old and
      those with higher Risk Adjustment in Congenital Heart Surgery-1 scores would have
      an increased risk of SSIs, but not an increased risk of BSIs after surgery.
      METHODS: We performed a retrospective cohort study of infants younger than 1 year
      of age undergoing cardiac surgery from January 2010 to December 2011 to determine
      the rates of SSIs and BSIs occurring within 3 months of surgery, risk factors
      associated with these infections, and causative pathogens. Multivariable
      associations using Cox proportional hazard modeling assessed potential risk
      factors for BSIs or SSIs. RESULTS: Overall, 8.7% (48 of 552) of surgical
      procedures were complicated by SSIs (n = 19) or BSIs (n = 29). Thus, SSIs and
      BSIs occurred after 3.4% and 5.3% of procedures, respectively. Multivariate
      models found age younger than 30 days, incorrect timing of preoperative
      antibiotics, and excessive bleeding within 24 hours of surgery to be significant
      predictors for SSIs, and duration of use of arterial lines to be a significant
      predictor for BSIs. Gram-positive bacteria caused 75% of SSIs and BSIs and
      methicillin-susceptible Staphylococcus aureus caused 63% of SSIs. DISCUSSION: We
      identified some potential strategies to reduce risk, including closer monitoring
      of timing of preoperative antimicrobial prophylaxis and enhanced efforts to
      achieve intraoperative hemostasis and earlier removal of arterial lines.
      CONCLUSIONS: SSIs and BSIs remain important complications after cardiac surgery
      in infants.

PMID- 24113024
TI  - Hospital costs associated with depression in a cohort of older men living in
      Western Australia.
AB  - BACKGROUND: There is lack of information of the hospital costs related to
      depression. Here, we compare the costs associated with general hospital
      admissions over 2 years between older men with and without a documented past
      history of depression. METHODS: A community-based cohort of older men living in
      Perth, Western Australia, was assessed at baseline between 2001 and 2004 and
      followed up for 2 years by prospective data linkage. The participants were
      selected randomly from the Australia electoral roll. Two-year hospital costs were
      estimated. RESULTS: Among 5411 patients, 75% of 339 men with depressive symptoms
      had at least one hospital admission compared with 61% of 5072 men without
      depression (P<.001). Two-year median hospital costs in the depressed group were
      A$4153 compared with A$1671 in participants free from depression (P<.001). In
      multivariate analysis, the presence of clinically significant depressive symptoms
      remained an independent predictor of higher cost [incident rate ratios (RR)=1.44,
      95% confidence interval (CI): 1.23-1.68] and was associated with being a high
      cost user of health services (RR=2.04, 95% CI: 1.43-2.92). LIMITATIONS: The
      estimation of costs was solely based on the main diagnosis, potentially leading
      to underestimates of the real cost differences. CONCLUSIONS: Hospital care cost
      was higher for older men with documented evidence of past depression than those
      without. The issue of depression in later life must be tackled if we want to
      optimize the use of limited hospital resources available.

PMID- 24113025
TI  - Aptitude-treatment interaction effects in psychooncological interventions.
AB  - OBJECTIVE: To examine aptitude-treatment interaction (ATI) effects in cancer
      patients receiving psychooncological interventions (POIs). METHOD: N=36 cancer
      patients were treated with POI. Hierarchical linear regression was used to test
      two interaction effects between patient baseline characteristics (aptitudes) and
      process analyses of therapy sessions (treatment) on change in mental health
      during POI. RESULTS: Patients with high emotional distress did best when their
      therapy reduced arousal, and patients with lower emotional distress benefited
      most if therapists emphasized arousal induction. The interaction between the
      coping style of the patient (internalizing vs. externalizing) and the focus of
      the treatment (emotion vs. behavior) did not predict POI outcomes. CONCLUSIONS:
      The ATI effect of patient's distress and therapist's arousal induction/reduction
      may help therapists to make differential treatment decisions in POI. Tailoring
      treatments to cancer patients based on their personal characteristics may enhance
      the effectiveness of POI.

PMID- 24113026
TI  - Phase resetting and its implications for interval timing with intruders.
AB  - Time perception in the second-to-minutes range is crucial for fundamental
      cognitive processes like decision making, rate calculation, and planning. We used
      a striatal beat frequency (SBF) computational model to predict the response of an
      interval timing network to intruders, such as gaps in conditioning stimulus (CS),
      or distracters presented during the uninterrupted CS. We found that, depending on
      the strength of the input provided to neural oscillators by the intruder, the SBF
      model can either ignore it or reset timing. The significant delays in timing
      produced by emotionally charged distracters were numerically simulated by a
      strong phase resetting of all neural oscillators involved in the SBF network for
      the entire duration of the evoked response. The combined effect of emotional
      distracter and pharmacological manipulations was modeled in our SBF model by
      modulating the firing frequencies of neural oscillators after they are released
      from inhibition due to emotional distracters. This article is part of a Special
      Issue entitled: SI: Associative and Temporal Learning. 

PMID- 24113027
TI  - Degradation of nitrobenzene in aqueous solution by dual-pulse ultrasound enhanced
      electrochemical process.
AB  - The present work reports a novel dual-pulse ultrasound enhanced electrochemical
      degradation (US-ECD) process that synchronizes alternatively ultrasound pulses
      and potential pulses to degrade nitrobenzene in aqueous solution with a high
      percentage degradation and low energy consumption. In comparison to the test
      results generated from the conventional US-ECD and original electrochemical
      degradation (ECD) process, the dual-pulse US-ECD process increased degradation
      percentages to nitrobenzene by 2% and 17%, respectively, while energy used in the
      pulse process was only about 46.5% of that was used in the conventional US-ECD
      process. Test results demonstrated a superior performance of the dual-pulse US
      ECD process over those of other conventional ones. Impacts of pulse mode, initial
      pH value, cell voltage, supporting electrolyte concentration and ultrasonic power
      on the process performances were investigated. With operation conditions
      optimized in the study at pH=3.0, cell voltage=10 V, ultrasonic power=48.84 W,
      electrolyte concentration=0.1M and an experiment running time of 30 min, the
      percentage degradation of nitrobenzene could reach 80% (US pulse time=50 ms and
      ECD pulse time=50 ms). This process provided a reliable and effective technical
      approach to degrade nitrobenzene in aqueous solution and significantly reduced
      energy consumption in comparison to the conventional US-ECD or original ECD
      treatment.

PMID- 24113029
TI  - SNX18 tubulates recycling endosomes for autophagosome biogenesis.
AB  - The role of membrane remodeling and phosphoinositide-binding proteins in
      autophagy remains elusive. PX domain proteins bind phosphoinositides and
      participate in membrane remodeling and trafficking events and we therefore
      hypothesized that one or several PX domain proteins are involved in autophagy.
      Indeed, the PX-BAR protein SNX18 was identified as a positive regulator of
      autophagosome formation using an image-based siRNA screen. We show that SNX18
      interacts with ATG16L1 and LC3, and functions downstream of ATG14 and the class
      III PtdIns3K complex in autophagosome formation. SNX18 facilitates recruitment of
      ATG16L1 to perinuclear recycling endosomes, and its overexpression leads to
      tubulation of ATG16L1- and LC3-positive membranes. We propose that SNX18 promotes
      LC3 lipidation and tubulation of recycling endosomes to provide membrane for
      phagophore expansion. 

PMID- 24113030
TI  - Progesterone receptor membrane component 1/Sigma-2 receptor associates with
      MAP1LC3B and promotes autophagy.
AB  - Autophagy resembles a recycling process in which proteins, organelles, or regions
      of the cytoplasm are enveloped and degraded. We have found that two of the
      central autophagy proteins, MAP1LC3 (microtubule-associated protein 1 light chain
      3, also described as LC3) and UVRAG (UV radiation resistance associated/UV
      radiation associated gene), complex with PGRMC1/S2R (progesterone receptor
      membrane component 1, also known as sigma-2 receptor). PGRMC1 is a cytochrome
      that is induced in cancer and is essential for tumor formation, invasion, and
      metastasis. Autophagy contributes to the turnover of long-lived and/or
      ubiquitinated proteins and the clearance of damaged organelles, and we have shown
      that PGRMC1 promotes both processes. Inhibition of PGRMC1 by RNAi or small
      molecule inhibitors causes autophagy substrates to increase and aberrant
      mitochondria to accumulate. We propose that this disruption of autophagy upon
      PGRMC1 inhibition increases AMPK activation, elevating the levels of TSC1
      (tuberous sclerosis complex) and TSC2 and inactivating MTOR and RPS6KB/p70S6K,
      causing cleaved MAP1LC3B levels to increase. Thus, PGRMC1 binds to key components
      of the autophagy machinery and is required for the degradative activity of
      autophagy. 

PMID- 24113031
TI  - Evolutionarily conserved role and physiological relevance of a STX17/Syx17
      (syntaxin 17)-containing SNARE complex in autophagosome fusion with endosomes and
      lysosomes.
AB  - Phagophores engulf cytoplasmic material and give rise to autophagosomes, double
      membrane vesicles mediating cargo transport to lysosomes for degradation. The
      regulation of autophagosome fusion with endosomes and lysosomes during autophagy
      has remained poorly characterized. Two recent papers conclude that STX17/syntaxin
      17 (Syx17 in Drosophila) has an evolutionarily conserved role in autophagosome
      fusion with endosomes and lysosomes, acting in one SNARE complex with SNAP29
      (ubisnap in Drosophila) and the endosomal/lysosomal VAMP8 (CG1599/Vamp7 in
      Drosophila). Surprisingly, a third report suggests that STX17 might also
      contribute to proper phagophore assembly. Although several experiments presented
      in the two human cell culture studies yielded controversial results, the
      essential role of STX17 in autophagic flux is now firmly established, both in
      cultured cells and in an animal model. Based on these data, we propose that
      genetic inhibition of STX17/Syx17 may be a more specific tool in autophagic flux
      experiments than currently used drug treatments, which impair all lysosomal
      degradation routes and also inactivate MTOR (mechanistic target of rapamycin), a
      major negative regulator of autophagy. Finally, the neuronal dysfunction and
      locomotion defects observed in Syx17 mutant animals point to the possible
      contribution of defective autophagosome clearance to various human diseases. 

PMID- 24113032
TI  - Distinct electrophysiological potentials for intention in action and prior
      intention for action.
AB  - The role of conscious intention in relation to motoric movements has become a
      major topic of investigation in neuroscience. Traditionally, reports of conscious
      intention have been compared to various features of the readiness-potential (RP)-
      an electrophysiological signal that appears before voluntary movements.
      Experiments, however, tend to study intentions in immediate relation to movements
      (proximal intentions), thus ignoring other aspects of intentions such as planning
      or deciding in advance of movement (distal intentions). The current study
      examines the difference in electrophysiological activity between proximal
      intention and distal intention, using electroencephalography (EEG). Participants
      had to form an intention to move and then wait 2.5 sec before performing the
      actual movement. In this way, the electrophysiological activity related to
      forming a conscious intention was separated from any confounding activity related
      to automated motor activity. This was compared to conditions in which
      participants had to act as soon as they had the intention and a condition where
      participants acted upon an external cue 2.5 sec prior to movement. We examined
      the RP for the three conditions. No difference was found in early RP, but late RP
      differed significantly depending on the type of intention. In addition, we
      analysed signals during a longer time-interval starting before the time of distal
      intention formation until after the actual movement concluded. Results showed a
      slow negative electrophysiological "intention potential" above the mid-frontal
      areas at the time participants formed a distal intention. This potential was only
      found when the distal intention was self-paced and not when the intention was
      formed in response to an external cue.

PMID- 24113033
TI  - [Rotational coronary atherectomy remains an important strategy in the era of drug
      eluting stents].

PMID- 24113034
TI  - [Explanation of comparative studies on global burden of disease between 1990 and
      2010].

PMID- 24113035
TI  - [Safety and efficacy of rotational atherectomy followed by drug-eluting stenting
      for treating patients with heavily calcified coronary lesions].
AB  - OBJECTIVE: To investigate the safety and efficacy of rotational atherectomy
      followed by drug-eluting stent implantation for treating patients with heavily
      calcified coronary lesions. METHODS: From March 1, 2010 to September 1, 2012, 65
      cases with 78 heavily calcified coronary lesions which were treated with
      rotational atherectomy followed by drug-eluting stent implantation in Peking
      University People's Hospital were included, and 36 cases also underwent
      intravascular ultrasound to guide the rotational atherectomy procedure and drug
      eluting stent implantation.All patients were followed up in hospital and post
      discharge. Procedure parameters, complications and major adverse cardiovascular
      events (cardiac death, non-fatal myocardial infarction, percutaneous coronary
      intervention related myocardial infarction, target vessel revascularization,
      recurrent angina, intra-stent restenosis and stent thrombosis) were analyzed.
      RESULTS: Direct rotational atherectomy was performed in 64.6%(42/65) patients,
      rescued rotational atherectomy in 35.4%(23/65) patients, drug-eluting stents
      implantation was applied to all cases after rotational atherectomy. The immediate
      procedural success rate was 100% (78/78). The average burr/artery ratio was 0.50
      +/- 0.04, the average number of burr used per case was 1.15 +/- 0.36. The average
      burr/artery ratio was 0.52 +/- 0.03 and the average number of burr used per cases
      was 1.19 +/- 0.40 in 36 cases guided with intravascular ultrasound. Five cases
      (7.7%) developed complications and were treated accordingly during procedure with
      satisfactory results. The incidence of major adverse cardiovascular events was
      13.8% (9/65) during (17.6 +/- 8.5) months follow-up. CONCLUSION: Rotational
      atherectomy followed by drug-eluting stent implantation is a safe and efficient
      technique for treating heavily calcified coronary lesions.

PMID- 24113036
TI  - [Clinical outcomes of rotational atherectomy followed by drug-eluting stenting
      via the transradial approach for the treatment of heavily calcified coronary
      lesions].
AB  - OBJECTIVE: To assess the clinical outcomes of rotational atherectomy followed by
      drug-eluting stenting via the transradial approach for the treatment of heavily
      calcified coronary lesions. METHODS: From January 2009 to October 2012, 114
      consecutive patients with heavily calcified coronary lesions underwent rotational
      atherectomy and drug-eluting stents via transradial approach in our hospital were
      enrolled in this retrospective study. Characteristics of heavily calcified
      coronary lesions, the success rates of rotational atherectomy and stenting, rates
      of complication during perioperative treatments, and adverse cardiovascular
      events during hospitalization and follow up were analyzed. RESULTS: All 114
      patients were successfully treated with rotational atherectomy and drug-eluting
      stent placement, and totally 120 target lesions of type B or C were treated
      including 8 left main lesions, 93 left anterior descending and 2 circumflex, 17
      right coronary lesions. No-reflow was observed in 7 patients during the
      procedure, there was one case of entrapped rotablator burr which was successfully
      retrieved together with guiding catheter without serious complication. During the
      6 months (median) follow-up, angina was reported in 11 patients and
      revascularization was performed in 8 patients due to stent restenosis and
      intensified medical therapy was applied in 3 patients. There was no acute
      myocardial infarction and death during follow-up. CONCLUSION: Rotational
      atherectomy followed by drug-eluting stenting via transradial approach is
      feasible, effective and safe and the short-term outcome is satisfactory for
      patients with heavily calcified coronary lesions.

PMID- 24113037
TI  - [Feasibility and outcome of rotational atherectomy for treating resistant chronic
      total occlusions].
AB  - OBJECTIVE: To assess the application of rotational atherectomy to improving the
      success rate and outcome of percutaneous recanalization of resistant chronic
      total occlusion (CTO), i.e. the guidewire could cross the lesion but it is
      impossible to advance any device over the wire through the occluded segment.
      METHODS: From August 2008 to December 2012, 26 consecutive patients with 27
      resistant CTO lesions were additionally treated by high-speed rotational
      atherectomy (rotational atherectomy group). The control group included 751 non
      resistant CTO lesions. Drug-eluting stents were implanted in two groups after the
      balloon catheter crossed the CTO lesions. The successful rate of rotational
      atherectomy and in hospital major adverse cardiovascular events (including
      cardiac death, interventional treatment related myocardial infarction and target
      vessel revascularization) were observed. RESULTS: The rate of heavily calcified
      coronary lesions was significantly higher in rotational atherectomy group than in
      the control group[63.0% (17/27) vs. 21.2% (159/751), P < 0.05] according to pre
      procedural coronary angiography. Rotational atherectomy was successful in 25 out
      of 27 resistant CTO lesions (92.6 %). The rate of cardiac death [0 vs. 0.5%
      (4/751), P > 0.05], interventional treatment related myocardial infarction [38.5%
      (10/26) vs. 22.2% (167/751), P > 0.05] and target vessel revascularization [0 vs.
      1.2% (9/751), P > 0.05] were similar between the rotational atherectomy group and
      the control group. CONCLUSION: Rotational atherectomy is a safe and helpful
      technique to overcome the inability of balloon catheter to cross a resistant CTO.

PMID- 24113038
TI  - [Analysis of coronary rotational atherectomy related complications].
AB  - OBJECTIVE: To analysis the complications of coronary rotational atherectomy and
      evaluate the safety of this procedure. METHOD: A total of 250 rotational
      atherectomy cases from April 1994 to February 2012 were screened retrospectively
      and 22 cases patients (8.8%) with rotational atherectomy-related complications
      were included in this analysis. RESULTS: Among these 22 patients, all lesions
      were either type B2 or C calcified lesions as evidenced by coronary angiography.
      After the rotation procedure, there were seven cases (2.8%) with slow reflow and
      two (0.8%) cases with no reflow. Seven cases (2.8%) developed severe coronary
      spasm and two cases (0.8%) had sinus bradycardia. Coronary dissection occurred in
      two cases (0.8%), while one case (0.4%) had coronary perforation and cardiac
      tamponade. Burr entrapment happened in one case (0.4%). There was no malignant
      arrhythmia, acute myocardial infarction, emergent coronary artery bypass graft or
      device related death during and post procedure. Comparison with baseline data,
      the concentration of CK-MB elevated significantly after the rotational
      atherectomy [(31.2 +/- 4.8) mmol/L vs. (11.4 +/- 6.5) mmol/L, P < 0.05].
      CONCLUSION: Coronary rotational atherectomy is safe and procedure-related
      complications are rare.

PMID- 24113039
TI  - [Anticoagulant efficacy and safety of argatroban for patients undergoing elective
      percutaneous coronary intervention].
AB  - OBJECTIVE: To investigate the anticoagulant efficacy and safety of argatroban for
      patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A
      total of 300 consecutive patients with coronary heart disease undergoing elective
      PCI were enrolled and randomized into heparin group (100 U/kg via artery sheaths,
      n = 150) and argatroban group (200 ug/kg bolus, followed by 350 ug.kg(-1).h(-1)
      i.v. infusion, n = 150). The primary efficacy endpoint was the activated clotting
      time (ACT) results (10 min and 60 min after anticoagulant administration and at
      the point at the end of PCI). The additional dosage of heparin or argatroban was
      given if the ACT value during PCI procedure < 250 s. Activated partial
      thromboplastin time (APTT) was also measured at pre-procedure, 10 min after
      anticoagulant injection and 60 min after PCI. The primary safety endpoint was
      thrombosis and hemorrhagic events during PCI procedure and hospital stay.
      RESULTS: All patients in the two groups attained the target ACT ( >= 250 s), and
      ACT in heparin group was significantly prolonged [(343.32 +/- 44.70) s vs.
      (289.60 +/- 20.88) s, P < 0.01], at 10 min after anticoagulation injection. ACT
      was similar between the two groups at 60 min after anticoagulation injection
      [(291.26 +/- 46.79) s vs. (288.40 +/- 21.61) s, P > 0.05]. The ACT value in
      argatroban group was similar at 10 min and 60 min after injection (P > 0.05).
      Supplemental anticoagulant was needed for 13 (8.7%) patients in heparin group and
      2 (1.3%) patients in argatroban group because of ACT under 250 s (P < 0.05) . At
      the end of PCI procedure, ACT in heparin group was significantly shorter than in
      argatroban group [(247.16 +/- 41.38)s vs. (278.65 +/- 20.51) s, P < 0.01]. APTT
      in heparin group was significantly prolonged than in argatroban group not only at
      10 min point [(182.16 +/- 4.37) s vs. (81.69 +/- 21.49) s, P < 0.01] after
      anticoagulant injection but also at the point of 60 min after PCI
      procedure[(169.13 +/- 6.35)s vs. (56.21 +/- 15.68) s, P < 0.01]. There was no
      thrombus event in two groups and no bleeding event in argatroban group, and there
      was three bleeding events in heparin group [2.0% (3/150) vs.0, P > 0.05].
      CONCLUSION: Argatroban is an effective and safe anticoagulation agent during
      elective PCI procedure, anticoagulant efficacy and risk of bleeding side effects
      of argatroban are similar to heparin.

PMID- 24113040
TI  - [Blood pressure lowering efficacy of telmisartan and amlodipine taking on the
      morning or at bedtime: ABPM results].
AB  - OBJECTIVE: To observe the blood lowering effect of telmisartan and amlodipine
      taking on the morning or at bedtime in hypertensive patients. METHODS: A total of
      108 individuals with hypertension (grade 2 or above) were randomized to receive
      telmisartan and amlodipine in one of the following four therapeutic schemes:
      Group A (26 cases): both medications taken on the morning; Group B (28 cases):
      both medication taken at bedtime; Group C (27 cases): telmisartan on the morning
      and amlodipine at bedtime; or Group D (27 cases): amlodipine on the morning and
      telmisartan at bedtime. ABPM was performed before and after 8 weeks treatment.
      RESULTS: BP was significantly reduced in 4 groups and the value of 24 hours
      SBP/DBP decline for each group after treatment was 29.94/16.32, 31.37/18.35,
      29.49/17.30 and 25.80/15.51 mm Hg (1 mm Hg = 0.133 kPa) respectively (P < 0.05
      vs. baseline). SI (smooth index) of 24 hours SBP/DBP was 1.79/1.34, 2.07/1.54,
      1.70/1.43 and 1.55/1.32 respectively (P > 0.05). The night-time BP decline and
      the distributive difference of dipper, non-dipper, extreme dipper and reverse
      dipper pattern were similar among groups at both baseline and after various
      treatment regimens (all P > 0.05) . Morning blood pressure surge (MBPS) after
      treatment in group B declined more significantly than other groups (P < 0.05).
      CONCLUSION: Telmisartan/amlodipine administered either on the morning or at
      bedtime can effectively reduce blood pressure. The efficacy of BP lowering is
      independent of the drug taking time. There is a trend both in better BP lowering
      and less BP variability when two medications are administered at bedtime.

PMID- 24113041
TI  - [Effects of policosanol combined with simvastatin on serum lipids and sex
      hormones in male patients with hyperlipidemia].
AB  - OBJECTIVE: To evaluate the effects and safety of policosanol combined with
      simvastatin on serum lipids and sex hormones in male patients with
      hyperlipidemia. METHODS: This randomized, single-blinded, placebo-controlled
      study included 120 male patients with hyperlipidemia. Patients were divided
      randomly into treatment group(n = 60) and control group(n = 60). Patients in the
      treatment group were administrated with simvastatin (40 mg/d) plus policosanol
      (20 mg/d),and those in the control group were treated with simvastatin (40 mg/d)
      plus placebo (20 mg/d). The values of total cholesterol(TC), triglyceride(TG),
      high density lipoprotein cholesterol (HDL-C), low-density lipoprotein
      cholesterol(LDL-C), testosterone(T) and estradiol (E2) were assessed before and
      after 16 weeks treatment.Drug-induced adverse effects were observed. RESULTS:
      Baseline characteristics were similar between groups. TC,TG, LDL-C were (5.74 +/-
      0.99) , (1.62 +/- 0.69), (3.60 +/- 0.56) mmol/L in the treatment group at
      baseline and significantly reduced after 16 weeks treatment (4.57 +/- 0.58),
      (1.54 +/- 0.55), (2.68 +/- 0.38) mmol/L (all P < 0.05). TC, LDL-C were (5.99 +/-
      0.93) , (3.76 +/- 0.42) mmol/L in the control group at baseline and significantly
      reduced after 16 weeks treatment (5.03 +/- 0.59) , (2.98 +/- 0.28) mmol/L (all P
      < 0.05) while TG remained unchanged post 16 weeks therapy in the control group.
      Simvastatin plus policosanol achieved a significantly greater reduction in LDL-C
      and TC than simvastatin plus placebo (P < 0.05). HDL-C,T and E2 were similar
      before and after 16 weeks treatments in both groups (P > 0.05) .The adverse
      reactions were similar between the two groups, most of them were mild and
      happened at the beginning of drug therapy and could be well tolerated.
      CONCLUSION: Simvastatin/policosanol produces greater decreases in TC, LDL-C than
      simvastatin/placebo without resulting more side effects and changes on sex
      hormones.

PMID- 24113042
TI  - [Effects of ambrisentan in treatment of pulmonary arterial hypertension: a pilot
      study with 15 patients].
AB  - OBJECTIVE: To investigate the preliminary efficacy and safety of ambrisentan, a
      selective endothelin receptor antagonist, in patients with pulmonary arterial
      hypertension (PAH). METHODS: A total of 15 patients with PAH, including 10
      patients with idiopathic PAH and 5 patients with associated connective-tissue
      disease, received 2.5 mg or 5 mg of ambrisentan once daily for 12 weeks. Before
      and after 12 weeks treatment, 6-minute walk test (6-MWD), WHO functional
      classification (WHO FC) and N-terminal pro-brain natriuretic peptide (NT-proBNP)
      were measured. RESULTS: After 12 weeks treatment, the 6-MWD was significantly
      increased [(376.5 +/- 108.2) m vs.(460.3 +/- 95.7) m, P = 0.021] and the systolic
      pulmonary artery was significantly decreased [(85.0 +/- 33.3) mm Hg (1 mm Hg =
      0.133 kPa)vs. (70.5 +/- 30.5) mm Hg,P = 0.015] and NT-proBNP was significantly
      reduced [892.0 (99.0-2245.0) ng/L vs. 205.0 (56.0-534.0) ng/L, P = 0.026] than
      before treatment. WHO FC was improved in 4 patients after 12 weeks treatment. No
      patient was withdrawn from this study for safety reasons. CONCLUSIONS:
      Ambrisentan treatment can effectively improve the exercise capacity, and reduce
      systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan use
      is safe and could be well tolerated in Chinese PAH patients.

PMID- 24113043
TI  - [Value of cardiopulmonary exercise test in assessment of cardiac function of
      patients with pulmonary hypertension].
AB  - OBJECTIVE: To explore the role of peak oxygen consumption in assessment of heart
      function of patients with pulmonary hypertension. METHODS: From September 2010 to
      April 2012, 101 patients [29 male, mean age: (32.6 +/- 11.4 )years] with
      pulmonary hypertension diagnosis by right heart catheterization were enrolled.
      Correlations among peak oxygen consumption, New York Heart Association (NYHA)
      class, NT-proBNP, 6 minute walking distance (6MWD) and cardiac index are
      analyzed. RESULTS: There were 44 cases with NYHA class II (43.6%), 49 cases with
      NYHA class III (48.5%), mean 6MWD was (421 +/- 91 )m, NT-proBNP was (1262 +/-
      816) ng/L, pulmonary vascular resistance was (1031 +/- 582) dyn.s(-1).cm(-5), CI
      was (3.5 +/- 2.3) L.min(-1).m(-2), peak oxygen consumption was( 13.8 +/-
      4.1)ml.min(-1).kg(-1). 6MWD, pulmonary vascular resistance and peak oxygen
      consumption were related to CI (r = 0.299, -0.541, 0.341, respectively, all P <
      0.05), but NYHA class and NT-proBNP were not correlated to CI. Multiple
      regression analysis demonstrated that peak oxygen consumption (B = 0.135, P =
      0.004) but not 6MWD was correlated with CI after adjusting age, sex and pulmonary
      vascular resistance. ROC analysis found that the sensitivity and specificity
      using peak oxygen consumption <15.2 ml.min(-1).kg(-1) as a cut-off value was
      92.6% and 57.5%, respectively, for diagnosing severe heart dysfunction.
      CONCLUSIONS: The correlation between peak oxygen consumption and CI is better
      than that of NYHA class, 6MWD, and NT-proBNP with CI. Peak oxygen consumption
      less than 15.2 ml.min(-1).kg(-1) could be used to detect reduced CI in patients
      with pulmonary hypertension.

PMID- 24113044
TI  - [Pretreatment with cyclosporin A nanoparticles emulsion protects apoptosis of
      swine adipose tissue-derived stem cells].
AB  - OBJECTIVE: To investigate the effect of cyclosporine A-nanoparticles emulsion
      (CsA-NP) on protecting apoptosis of swine adipose tissue-derived stem cells (ASC
      ) and related mechanisms. METHODS: ASC were randomized to six groups: control
      group,single H2O2 group,CsA or CsA-NP 0.1 mg/ml+H2O2 group,CsA or CsA-NP 1.0
      mg/ml+H2O2 group, CsA or CsA-NP 5.0 mg/ml+H2O2 group,CsA or CsA-NP 10.0
      mg/ml+H2O2 group. ASC apoptosis was induced by hydrogen peroxide (H2O2100 umol/L)
      in vitro. The morphology of apoptotic cells was observed and the number of
      apoptotic cells was measured. Apoptosis of ASC was detected by flow cytometry
      using an apoptosis kit. Cell activity was determined by CCK-8 assay. Caspase-3
      activity was detected by applying a caspase-3 assay kit. Expression of cytochrome
      C was investigated by Western blot. RESULTS: H2O2 induced ASC apoptosis was
      evidenced by morphological and biochemical changes,which could be significantly
      reduced by pre-treatment with CsA or CsA-NP at concentration of 0.1-10.0 mg/ml,
      and the best effect was observed at concentration of 5 mg/ml (apoptosis rate:
      CsA: 10.6% +/- 2.8% vs. 25.2% +/- 3.8%; CsA-NP: 6.2% +/- 2.6% vs. 25.2% +/- 3.6%
      in control group, all P < 0.01). The cell activity was significantly higher in
      CsA or CsA-NP pre-treated ASC at concentration of 0.1-10.0 mg/ml than in H2O2
      group (P < 0.01). Pre-treatment with CsA or CsA-NP (0.1-10.0 mg/ml) significantly
      down -regulated caspase-3 activity. Furthermore, CsA or CsA-NP (5 mg/ml)
      completely inhibited the H2O2-induced release of cytochrome C. CONCLUSIONS: These
      results suggest that CsA-NP and CsA could protect the oxidative stress-induced
      ASC apoptosis through decreasing the activation of caspase-3 and inhibiting the
      release of cytochrome C.

PMID- 24113045
TI  - [MicroRNA-133a attenuates isoproterenol-induced neonatal rat cardiomyocyte
      hypertrophy by downregulating L-type calcium channel alpha1C subunit gene
      expression].
AB  - OBJECTIVE: To investigate the effects of microRNA-133a on isoproterenol (ISO)
      induced neonatal rat cardiomyocyte hypertrophy and related molecular mechanism
      focusing on the changes of L-type calcium channel alpha1C subunit. METHODS:
      Neonatal rat cardiomyocytes were cultured, cardiomyocyte hypertrophy was induced
      by isoproterenol (ISO, 10 umol/L). The cell surface area was measured by phase
      contrast microscope and Leica image analysis system. The mRNA expressions of
      atrial natriuretic peptide (ANP), beta-myosin heavy chain (beta-MHC), miR-133a
      and the alpha1C were detected by qRT-PCR. The protein expression of alpha1C was
      evaluated by Western blot. MiR-133a mimic was transfected into cardiomyocytes to
      investigate the effects of miR-133a on ISO-induced cardiomyocyte hypertrophy. The
      targets of miR-133a were predicted by online database Targetscan. The 3'
      untranslated region sequence of alpha1C was cloned into luciferase reporter
      vector and then transiently transfected into HEK293 cells. The luciferase
      activities of samples were measured to verify the expression of luciferase
      reporter vector. The expression level of alpha1C was inhibited by RNAi to
      determine the effects of alpha1C on cardiomyocyte hypertrophy. Intracellular
      Ca(2+) content was measured by confocal laser microscope. RESULTS: (1) The
      expression of miR-133a was significantly reduced in ISO-induced cardiomyocyte
      hypertrophy (P < 0.01) . Upregulating miR-133a level could suppress the increase
      of cell surface area, the mRNA expression of ANP and beta-MHC (P < 0.01) . (2)
      alpha1C was the one of potential target of miR-133a by prediction using online
      database Targetscan. The luciferase activities of HEK293 cells with the plasmid
      containing wide type alpha1C 3'UTR sequence were significantly decreased compared
      with control group (P < 0.01) . Upregulation of the miR-133a level by miR-133a
      mimic transfection could suppress the protein expression of alpha1C (P < 0.05) .
      (3) The expression of alpha1C was significantly increased in ISO treated
      cardiomyocytes (P < 0.05) . Downregulation of alpha1C by RNAi could markedly
      inhibit the increase of cell surface area, the mRNA expression of ANP and beta
      MHC (P < 0.01, P < 0.05, P < 0.05). (4) Downregulation of alpha1C expression by
      RNAi or upregulation of miR-133a level by miR-133a mimic transfection
      significantly inhibited intracellular Ca(2+) content (P < 0.01) . CONCLUSIONS:
      Our data confirms that alpha1C is the target of miR-133a. MiR-133a can negatively
      regulate the expression of L-type calcium alpha1C subunit, resulting in the
      decrease of intracellular Ca(2+) content and the attenuation of ISO-induced
      cardiomyocyte hypertrophy.

PMID- 24113046
TI  - [Impact of baseline pulse pressure on new-onset cardio-and cerebrovascular events
      in diabetic population].
AB  - OBJECTIVE: To observe the association between baseline pulse pressure (PP) level
      and new-onset cardio-cerebrovascular events in diabetic population. METHODS:
      Physical examination data between July 2006 to October 2007 from a total of 101
      510 employees of Kailuan Group were reviewed, 8306 subjects with a fasting plasma
      glucose level of >= 7.0 mmol/L or with confirmed diabetes diagnosis and were
      enrolled in this prospective cohort study. Subjects were followed up for 38-53
      (48.1 +/- 3.1) months and the cardio-cerebrovascular events were obtained every
      six months, association between baseline PP and new-onset cardio-cerebrovascular
      events in the diabetic population were analyzed. RESULTS: (1) Incidences of total
      cardio-cerebrovascular events in the PP groups were 3.4%, 2.8%, 4.5%, 6.4%,
      respectively. Incidences of cerebral infarction events and myocardial infarction
      were 2.1%, 1.6%, 2.9%, 3.9% and 1.1%, 0.7%, 1.0%, 1.7%, respectively. (2)
      Multivariate Cox's proportional hazards regression analysis indicated that
      baseline PP group was the risk factor for total cardio-cerebrovascular events,
      cerebral infarction events and myocardial infarction, and the risk for all the
      events of the PP >= 60 mm Hg (1 mm Hg = 0.133 kPa) group was increasing. The
      values of RR(95%CI) were 1.88 (95%CI 1.34-2.65, P < 0.01), 1.92 (95%CI 1.23-2.99,
      P < 0.01) and 1.52 (95%CI 0.82-2.81, P > 0.05) after adjust the other factors.(3)
      In line with increasing level of baseline PP, age, BMI, SBP, DBP, HDL-C, and hs
      CRP levels significantly increased in this diabetic population (P < 0.01 or P <
      0.05). CONCLUSION: The level of high baseline PP is a risk factor for new-onset
      cardio-cerebrovascular events in diabetic population.

PMID- 24113047
TI  - [Myocardial infarction, pericardial effusion and right atrium mass in a patient
      with Behcet's disease].

PMID- 24113049
TI  - [Current research status on lifetime risk estimation of cardiovascular disease].

PMID- 24113048
TI  - [Acute myocardial infarction after anaphylactic reaction to wasps sting: a case
      report of Kounis syndrome].

PMID- 24113050
TI  - [Research update on Kounis syndrome].

PMID- 24113051
TI  - [Research progress in relationship between smads protein and cardiovascular
      diseases].

PMID- 24113052
TI  - Effects of constructivist teaching methods on bioethics education for nursing
      students: a quasi-experimental study.
AB  - BACKGROUND: In order to help nurses advocate for the patient's human rights and
      ensure respect for life in clinical situations, it is of utmost importance to
      improve nursing students' capacity to make ethical decisions. OBJECTIVES: This
      study compares the effects of two constructivist teaching strategies (action
      learning and cross-examination debate) on nursing students' recognition of
      bioethical issues, experience of bioethical issues, and attainment of ethical
      competence. DESIGN: This study used a quasi-experimental (two-group pretest
      posttest) design. SETTING: A nursing college in South Korea. PARTICIPANTS: A
      total of 93 Korean nursing students participated in the study (46 in the action
      learning group and 47 in the cross-examination debate group). METHODS:
      Participants took a bioethics class employing one or the other of the strategies
      mentioned, 2h a week for 15 weeks. All participants responded twice to a set of
      questionnaires, at the beginning of the first session and at the end of the last
      session. RESULTS: After their bioethics education, the students' recognition of
      bioethical issues improved for both classes; however, the knowledge of students
      who had participated in action learning improved more than that of the students
      in the debate-based class. Students in both groups reported more experience of
      bioethics and exposure to better-quality instruction in bioethics after their
      classes than previously. Students in both groups also reported improved ethical
      competency after this education. CONCLUSION: Positive effects of action learning
      and cross-examination debate implemented as teaching strategies on nursing
      students' understanding of bioethical issues and their ethical competency were
      identified; these findings will be important in the essential task of teaching
      bioethics to nursing students in order to foster more ethical decision-making and
      other ethical behavior.

PMID- 24113053
TI  - Taking another look at independent double checks.

PMID- 24113054
TI  - Subcellular spatial correlation of particle traversal and biological response in
      clinical ion beams.
AB  - PURPOSE: To report on the spatial correlation of physical track information
      (fluorescent nuclear track detectors, FNTDs) and cellular DNA damage response by
      using a novel hybrid detector (Cell-Fit-HD). METHODS AND MATERIALS: The FNTDs
      were coated with a monolayer of human non-small cell lung carcinoma (A549) cells
      and irradiated with carbon ions (270.55 MeV u(-1), rising flank of the Bragg
      peak). Phosphorylated histone variant H2AX accumulating at the irradiation
      induced double-strand break site was labeled (RIF). The position and direction of
      ion tracks in the FNTD were registered with the location of the RIF sequence as
      an ion track surrogate in the cell layer. RESULTS: All RIF sequences could be
      related to their corresponding ion tracks, with mean deviations of 1.09 MUm and 
      1.72 MUm in position and of 2.38 degrees  in slope. The mean perpendicular
      between ion track and RIF sequence was 1.58 MUm. The mean spacing of neighboring
      RIFs exhibited a regular rather than random spacing. CONCLUSIONS: Cell-Fit-HD
      allows for unambiguous spatial correlation studies of cell damage with respect to
      the intracellular ion traversal under therapeutic beam conditions.

PMID- 24113055
TI  - Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus
      intensity modulated radiation therapy on the high-dose arm of the Radiation
      Therapy Oncology Group 0126 prostate cancer trial.
AB  - PURPOSE: To give a preliminary report of clinical and treatment factors
      associated with toxicity in men receiving high-dose radiation therapy (RT) on a
      phase 3 dose-escalation trial. METHODS AND MATERIALS: The trial was initiated
      with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow
      intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a
      planning target volume that included the prostate and seminal vesicles, then 23.4
      Gy to prostate only. The IMRT patients were treated to the prostate and proximal
      seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation
      Therapy Oncology Group/European Organization for Research and Treatment of Cancer
      late morbidity scores were used for acute and late effects. RESULTS: Of 763
      patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126
      protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT
      and IMRT, respectively. For both bladder and rectum, the volumes receiving 65,
      70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+
      acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and
      multivariate analyses showed a statistically significant decrease in G2+ acute
      collective GI/GU toxicity for IMRT. There were no significant differences with 3D
      CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed
      a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039).
      On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity
      (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With
      dose-volume histogram data in the multivariate analysis, RT modality was not
      significant, whereas white race (P=.001) and rectal V70 >=15% were associated
      with G2+ rectal toxicity (P=.034). CONCLUSIONS: Intensity modulated RT is
      associated with a significant reduction in acute G2+ GI/GU toxicity. There is a
      trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT.
      The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are
      associated with late rectal toxicity.

PMID- 24113056
TI  - Hematopoietic stem and progenitor cell migration after hypofractionated radiation
      therapy in a murine model.
AB  - PURPOSE: To characterize the recruitment of bone marrow (BM)-derived
      hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment
      after radiation therapy (RT) in a murine, heterotopic tumor model. METHODS AND
      MATERIALS: Lewis lung carcinoma tumors were established in C57BL/6 mice and
      irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with
      positron emission tomography/computed tomography (PET/CT) and measured daily with
      digital calipers. The HSPC and myelomonocytic cell content was assessed via
      immunofluorescent staining and flow cytometry. Functionality of tumor-associated
      HSPCs was verified in vitro using colony-forming cell assays and in vivo by
      rescuing lethally irradiated C57BL/6 recipients. RESULTS: Irradiation
      significantly reduced tumor volumes and tumor regrowth rates compared with
      nonirradiated controls. The number of CD133(+) HSPCs present in irradiated tumors
      was higher than in nonirradiated tumors during all stages of regrowth. CD11b(+)
      counts were similar. PET/CT imaging and growth rate analysis based on
      standardized uptake value indicated that HSPC recruitment directly correlated to
      the extent of regrowth and intratumor cell activity after irradiation. The BM
      derived tumor-associated HSPCs successfully formed hematopoietic colonies and
      engrafted irradiated mice. Finally, targeted treatment with a small animal
      radiation research platform demonstrated localized HSPC recruitment to defined
      tumor subsites exposed to radiation. CONCLUSIONS: Hypofractionated irradiation
      resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly
      as a mechanism to promote tumor regrowth. These data indicate for the first time
      that radiation therapy regulates HSPC content within regrowing tumors.

PMID- 24113057
TI  - Hypofractionated radiation therapy for breast ductal carcinoma in situ.
AB  - PURPOSE: Conventional radiation therapy (RT) administered in 25 fractions after
      breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in
      situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16
      fractions have been shown to be equivalent to conventional RT for invasive breast
      cancer, few studies have reported results of using hypofractionated RT in DCIS.
      METHODS AND MATERIALS: In this multicenter collaborative effort, we
      retrospectively reviewed the records of all women with DCIS at 3 institutions
      treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in
      16 fractions. RESULTS: Between 2003 and 2010, 440 patients with DCIS underwent
      BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy
      (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients
      (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a
      median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse,
      resulting in a local recurrence-free survival of 97% at 5 years. Positive
      surgical margins, high nuclear grade, age less than 50 years, and a premenopausal
      status were all statistically associated with an increased occurrence of local
      recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and
      administration of additional boost RT did not have an impact on local control in
      our cohort. On multivariate analysis, positive margins, premenopausal status, and
      nuclear grade 3 tumors had a statistically significant worse local control rate.
      CONCLUSIONS: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent
      local control for patients with DCIS undergoing BCS.

PMID- 24113058
TI  - Combined recipe for clinical target volume and planning target volume margins.
AB  - PURPOSE: To develop a combined recipe for clinical target volume (CTV) and
      planning target volume (PTV) margins. METHODS AND MATERIALS: A widely accepted
      PTV margin recipe is M(geo) = aSigma(geo) + bsigma(geo), with Sigma(geo) and
      sigma(geo) standard deviations (SDs) representing systematic and random geometric
      uncertainties, respectively. On the basis of histopathology data of breast and
      lung tumors, we suggest describing the distribution of microscopic islets around
      the gross tumor volume (GTV) by a half-Gaussian with SD Sigma(micro), yielding as
      possible CTV margin recipe: M(micro) = f(N(i)) * Sigma(micro), with N(i) the
      average number of microscopic islets per patient. To determine f(N(i)), a
      computer model was developed that simulated radiation therapy of a spherical GTV
      with isotropic distribution of microscopic disease in a large group of virtual
      patients. The minimal margin that yielded D(min) <95% in maximally 10% of
      patients was calculated for various Sigma(micro) and N(i). Because Sigma(micro)
      is independent of Sigma(geo), we propose they should be added quadratically,
      yielding for a combined GTV-to-PTV margin recipe: M(GTV-PTV) = ?{[aSigma(geo)](2)
      + [f(N(i))Sigma(micro)](2)} + bsigma(geo). This was validated by the computer
      model through numerous simultaneous simulations of microscopic and geometric
      uncertainties. RESULTS: The margin factor f(N(i)) in a relevant range of
      Sigma(micro) and N(i) can be given by: f(N(i)) = 1.4 + 0.8log(N(i)). Filling in
      the other factors found in our simulations (a = 2.1 and b = 0.8) yields for the
      combined recipe: M(GTV-PTV) = ?({2.1Sigma(geo)}(2) + {[1.4 + 0.8log(N(i))] *
      Sigma(micro)}(2)) + 0.8sigma(geo). The average margin difference between the
      simultaneous simulations and the above recipe was 0.2 +/- 0.8 mm (1 SD).
      Calculating M(geo) and M(micro) separately and adding them linearly overestimated
      PTVs by on average 5 mm. Margin recipes based on tumor control probability (TCP)
      instead of D(min) criteria yielded similar results. CONCLUSIONS: A general recipe
      for GTV-to-PTV margins is proposed, which shows that CTV and PTV margins should
      be added in quadrature instead of linearly.

PMID- 24113059
TI  - Argon plasma coagulation therapy versus topical formalin for intractable rectal
      bleeding and anorectal dysfunction after radiation therapy for prostate
      carcinoma.
AB  - PURPOSE: To evaluate and compare the effect of argon plasma coagulation (APC) and
      topical formalin for intractable rectal bleeding and anorectal dysfunction
      associated with chronic radiation proctitis. METHODS AND MATERIALS: Thirty men
      (median age, 72 years; range, 49-87 years) with intractable rectal bleeding
      (defined as >=1* per week and/or requiring blood transfusions) after radiation
      therapy for prostate carcinoma were randomized to treatment with APC (n=17) or
      topical formalin (n=13). Each patient underwent evaluations of (1) anorectal
      symptoms (validated questionnaires, including modified Late Effects in Normal
      Tissues-Subjective, Objective, Management, and Analytic and visual analogue
      scales for rectal bleeding); (2) anorectal motor and sensory function (manometry
      and graded rectal balloon distension); and (3) anal sphincteric morphology
      (endoanal ultrasound) before and after the treatment endpoint (defined as
      reduction in rectal bleeding to 1* per month or better, reduction in visual
      analogue scales to <=25 mm, and no longer needing blood transfusions). RESULTS:
      The treatment endpoint was achieved in 94% of the APC group and 100% of the
      topical formalin group after a median (range) of 2 (1-5) sessions of either
      treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in
      each group needed further treatment. Reductions in rectal compliance and volumes
      of sensory perception occurred after APC, but no effect on anorectal symptoms
      other than rectal bleeding was observed. There were no differences between APC
      and topical formalin for anorectal symptoms and function, nor for anal
      sphincteric morphology. CONCLUSIONS: Argon plasma coagulation and topical
      formalin had comparable efficacy in the durable control of rectal bleeding
      associated with chronic radiation proctitis but had no beneficial effect on
      anorectal dysfunction.

PMID- 24113061
TI  - Synthesis and biological evaluation of hydrazidomycin analogues.
AB  - Hydrazidomycin A is an unusual secondary metabolite of Streptomyces atratus that
      features a rare enehydrazide core. To learn more about structure-activity
      relationships of the reported cytotoxic and antiproliferative agent several
      synthetic routes were explored to synthesize a variety of hydrazidomycin
      derivatives. Specifically, the size of the side chains, the nature of the double
      bond and the polar head group were altered. Overall, fourteen analogues were
      tested for their cytotoxic and antiproliferative effects. Re-examination of
      synthetic hydrazidomycin A suggests that the antiproliferative activity is
      attributed to a yet unknown compound that results from degradation or
      rearrangement. Several of the less complex analogues, however, show
      antiproliferative activities against individual cancer cell lines and turned out
      to be more potent than hydrazidomycin A. 

PMID- 24113060
TI  - Clinical implementation of intrafraction cone beam computed tomography imaging
      during lung tumor stereotactic ablative radiation therapy.
AB  - PURPOSE: To develop and clinically evaluate a volumetric imaging technique for
      assessing intrafraction geometric and dosimetric accuracy of stereotactic
      ablative radiation therapy (SABR). METHODS AND MATERIALS: Twenty patients
      received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At
      the beginning of each fraction, pretreatment cone beam computed tomography (CBCT)
      was used to align the soft-tissue tumor position with that in the planning CT.
      Concurrent with dose delivery, we acquired fluoroscopic radiograph projections
      during VMAT using the Varian on-board imaging system. Those kilovolt projections
      acquired during millivolt beam-on were automatically extracted, and intrafraction
      CBCT images were reconstructed using the filtered backprojection technique. We
      determined the time-averaged target shift during VMAT by calculating the center
      of mass of the tumor target in the intrafraction CBCT relative to the planning
      CT. To estimate the dosimetric impact of the target shift during treatment, we
      recalculated the dose to the GTV after shifting the entire patient anatomy
      according to the time-averaged target shift determined earlier. RESULTS: The mean
      target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the
      95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6,
      and 4.9 mm along the anterior-posterior, left-right, and superior-inferior
      directions. Thus, the time-averaged intrafraction gross tumor volume (GTV)
      position was always within the planning target volume. We observed some degree of
      target blurring in the intrafraction CBCT, indicating imperfect breath-hold
      reproducibility or residual motion of the GTV during treatment. By our estimated
      dose recalculation, the GTV was consistently covered by the prescription dose
      (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100%
      PD for 18 patients and >95% PD for all patients. CONCLUSIONS: Intrafraction CBCT
      during VMAT can provide geometric and dosimetric verification of SABR valuable
      for quality assurance and potentially for treatment adaptation.

PMID- 24113062
TI  - Investigation of aryl halides as ketone bioisosteres: refinement of potent and
      selective inhibitors of human cytochrome P450 19A1 (aromatase).
AB  - Bioisosteric replacement of cyclic ketone functionality with aryl halides was
      investigated on a centrally-flexible, five-component 1,2,3-triazole-containing
      pharmacophore, resulting in enhanced inhibition of aromatase (CYP450 19A1).
      Structure-activity data generated from both syn- and anti-aldol precursors
      provides significant insights into the requirements for enhanced potency,
      validating this novel ketone-to-aryl halide bioisostere hypothesis. 

PMID- 24113063
TI  - Introductory pictorial atlas of 3D tomosynthesis.
AB  - Mammography is an essential tool for early detection of breast cancer. Breast
      imaging based on three-dimensional digital breast tomosynthesis (DBT) is a new
      method for breast cancer screening and diagnosis that uses three-dimensional
      digital images to allow separation of overlapping breast structures, which may
      allow for improved visualization of potentially significant findings. This
      article will highlight the utility of DBT as a tool for the detection of breast
      pathology; it will demonstrate normal findings as well as breast pathology on DBT
      and two-dimensional conventional mammography. DBT is a very promising modality,
      which may decrease the false-positive rate of mammography and find additional
      abnormalities not seen on two-dimensional mammography. 

PMID- 24113064
TI  - Two different approaches to restore renal nitric oxide and prevent hypertension
      in young spontaneously hypertensive rats: l-citrulline and nitrate.
AB  - Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is
      involved in the development of hypertension. NO synthesis occurs via 2 pathways:
      nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the
      development of hypertension is prevented by restoration of NO by dietary l
      citrulline or nitrate supplementation in young spontaneously hypertensive rats
      (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks
      were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that
      received 0.25% l-citrulline for 8 weeks. In our second series of studies, we
      replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed
      at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented
      by dietary supplementation of l-citrulline or nitrate. Both treatments restored
      NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline
      therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an
      endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR
      kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA
      concurrently in SHRs. Our findings suggest that both NOS-dependent and 
      independent approaches in the prehypertensive stage toward augmentation of NO can
      prevent the development of hypertension in young SHRs. 

PMID- 24113065
TI  - Efficient and rapid derivation of primitive neural stem cells and generation of
      brain subtype neurons from human pluripotent stem cells.
AB  - Human pluripotent stem cells (hPSCs), including human embryonic stem cells and
      human induced pluripotent stem cells, are unique cell sources for disease
      modeling, drug discovery screens, and cell therapy applications. The first step
      in producing neural lineages from hPSCs is the generation of neural stem cells
      (NSCs). Current methods of NSC derivation involve the time-consuming, labor
      intensive steps of an embryoid body generation or coculture with stromal cell
      lines that result in low-efficiency derivation of NSCs. In this study, we report
      a highly efficient serum-free pluripotent stem cell neural induction medium that
      can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for
      time-consuming, laborious embryoid body generation or rosette picking. The pNSCs
      expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were
      negative for Oct4; could be expanded for multiple passages; and could be
      differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the
      brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor
      neurons. Global gene expression of the transcripts of pNSCs was comparable to
      that of rosette-derived and human fetal-derived NSCs. This work demonstrates an
      efficient method to generate expandable pNSCs, which can be further
      differentiated into central nervous system neurons and glia with temporal,
      spatial, and positional cues of brain regional heterogeneity. This method of pNSC
      derivation sets the stage for the scalable production of clinically relevant
      neural cells for cell therapy applications in good manufacturing practice
      conditions. 

PMID- 24113066
TI  - Generation of glycosylphosphatidylinositol anchor protein-deficient blood cells
      from human induced pluripotent stem cells.
AB  - PIG-A is an X-linked gene required for the biosynthesis of
      glycosylphosphatidylinositol (GPI) anchors; thus, PIG-A mutant cells have a
      deficiency or absence of all GPI-anchored proteins (GPI-APs). Acquired mutations
      in hematopoietic stem cells result in the disease paroxysmal nocturnal
      hemoglobinuria, and hypomorphic germline PIG-A mutations lead to severe
      developmental abnormalities, seizures, and early death. Human induced pluripotent
      stem cells (iPSCs) can differentiate into cell types derived from all three germ
      layers, providing a novel developmental system for modeling human diseases. Using
      PIG-A gene targeting and an inducible PIG-A expression system, we have
      established, for the first time, a conditional PIG-A knockout model in human
      iPSCs that allows for the production of GPI-AP-deficient blood cells. PIG-A-null
      iPSCs were unable to generate hematopoietic cells or any cells expressing the
      CD34 marker and were defective in generating mesodermal cells expressing
      KDR/VEGFR2 (kinase insert domain receptor) and CD56 markers. In addition, PIG-A
      null iPSCs had a block in embryonic development prior to mesoderm differentiation
      that appears to be due to defective signaling through bone morphogenetic protein
      4. However, early inducible PIG-A transgene expression allowed for the generation
      of GPI-AP-deficient blood cells. This conditional PIG-A knockout model should be
      a valuable tool for studying the importance of GPI-APs in hematopoiesis and human
      development. 

PMID- 24113067
TI  - Changing epidemiology of candidemia in a medical center in middle Taiwan.
AB  - BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the
      health care setting, and the epidemiology of Candida infection is changing.
      METHODS: Clinical and laboratory data from patients with candidemia were
      collected retrospectively at a tertiary medical center in Taiwan from July 1,
      2009 to June 30, 2012 (a 36-month period). Demographics, clinical
      characteristics, and drug susceptibility of the invading Candida species of
      patients at the onset of candidemia were analyzed and compared with previous
      study from January 1, 2001 to June 30, 2003 (a 30-month period). RESULTS: A total
      of 209 episodes of candidemia in 205 patients were identified in this study
      period. When compared with the previous study period, more patients were admitted
      for medical conditions at percentages ranging from 49.5% to 69.8%; the incidence
      rate of health care-associated candidemia increased from 0.76 to 1.14 per 1000
      discharges; the proportion of Candida albicans in patients with candidemia
      decreased from 64.8% to 43.6% whereas the proportion of Candida glabrata
      increased greatly from 1.1% to 21.6% and the proportions of Candida tropicalis
      and Candida parapsilosis were slightly elevated (19.8-22.0% and 2.2-7.3%,
      respectively). All of the C. albicans isolates remained susceptible to
      fluconazole, whereas 66.7% of C. glabrata isolates were dose-dependent
      susceptible, and 4.4% of C. glabrata isolates and 11.6% C. tropicalis isolates
      were resistant. There was one C. glabrata and one Candida guilliermondii
      resistant to echinocandin. The predictors for 30-day mortality included the high
      Acute Physiology and Chronic Health Evaluation II (APACHE II) score, use of
      parenteral nutrition, underlying malignancy, liver cirrhosis, and neutropenia
      whereas candidemia by C. parapsilosis or C. glabrata is a favorable predictor
      when compared with C. albicans. CONCLUSION: The distribution of Candida species
      in candidemia was changed. Although C. albicans remained the major species, the
      isolation of non-C. albicans spp., especially C. glabrata, increased. Patients
      with candidemia still had high mortalities due to severity of illness and
      underlying conditions.

PMID- 24113068
TI  - Prevalence of and associated factors with chronic kidney disease in human
      immunodeficiency virus-infected patients in Taiwan.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an important issue for individuals
      who live with human immunodeficiency virus (HIV) following the use of highly
      active antiretroviral therapy; however, the prevalence rate of CKD varies between
      countries. METHODS: The present study screened HIV-infected patients in a medical
      center and a regional teaching hospital in southern Taiwan from January 2008 to
      December 2012. CKD was defined as a urine microalbumin-to-creatinine ratio >=30
      mg/g, and/or a protein >=1 + on urine dipstick examination, and/or an estimated
      glomerular filtration rate <60 mL/min/1.73 m(2) for 3 months. The prevalence rate
      and the analyzed associated factors of CKD were determined. RESULTS: Among 1639
      HIV-infected patients, only 512 had adequate data to be enrolled in the study.
      Thirty-six (7.03%) of these patients had CKD, and 476 did not. In a univariate
      analysis, CKD was associated with an older age, a higher peak HIV RNA load,
      diabetes mellitus (DM), hypertension, exposure to antiretroviral therapy, and
      cholesterol levels >=240 mg/dL. Multivariate analysis revealed that DM,
      hypertension, and cholesterol >=240 mg/dL were statistically significant factors.
      CONCLUSION: In Taiwan, the prevalence of CKD in HIV-infected patients was low
      (7.03%). The classical risk factors for CKD, such as DM, hypertension, and
      hypercholesterolemia, were demonstrated to be associated with CKD in Taiwanese
      HIV-infected patients.

PMID- 24113069
TI  - Rapid identification of Mycobacterium avium clinical isolates by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry.
AB  - BACKGROUND: Rapid and accurate discrimination of Mycobacterium avium from other
      mycobacteria is essential for appropriate therapeutic management and timely
      intervention for infection control. However, routine clinical identification
      methods for M. avium are both time consuming and labor intensive. In the present
      study, matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) was used to identify specific cellular protein
      pattern for rapid identification of M. avium isolates. METHODS: A total of 40
      clinically relevant Mycobacterium strains comprising 13 distinct species were
      enrolled for the MALDI-TOF MS identification. A 10-minute extraction-free
      examination procedure was set up to obtain mass spectral fingerprints from whole
      bacterial cells. RESULTS: The characteristic mass spectral peak patterns in the
      m/z (mass/charge ratio) range of 5-20 kDa can be obtained within 10 minutes. The
      species-specific mass spectra for M. avium is identified and can be
      differentiated from as Mycobacterium strains. This technique shortens and
      simplifies the identification procedure of MALDI-TOF MS and may further extend
      the mycobacterial MALDI-TOF MS database. CONCLUSION: Simplicity and rapidity of
      identification procedures make MALDI-TOF MS an attractive platform in routine
      identification of mycobacteria. MALDI-TOF MS is applicable for rapid
      discrimination of M. avium from other Mycobacterium species, and shows its
      potential for clinical application.

PMID- 24113070
TI  - A report on the first outbreak of a single clone group A Streptococcus (emm-type
      89) tonsillopharyngitis in China.
AB  - In 2012, 28 out of 140 staff working for a film crew in a Beijing movie and
      television base experienced a sudden onset of fever, sore throat, and/or
      tiredness, headache within the 24 hour period of July 26-27. All of the patients
      visited the hospital and were diagnosed as having tonsillopharyngitis. On July
      28, 2012, a team of Centers for Disease Control and Prevention staff arrived and
      initiated an outbreak investigation. Pharyngeal swabs were obtained from patients
      for microbiologic analysis. All isolates of the outbreak were analyzed for toxin
      genes and drug-resistance genes by polymerase chain reaction, and were performed
      for the emm typing and pulsed-field gel electrophoresis typing. On July 30, 2012,
      Group A Streptococcus was isolated from eight of the 16 throat swab specimens
      obtained on site. These isolates were found to have the same genotype emm 89.
      This is the first report to identify Group A Streptococcus emm type-89 as a cause
      of tonsillopharyngitis in Beijing, China. 

PMID- 24113071
TI  - Development and characterization of a novel controlled release drug delivery
      system based on nanostructured lipid carriers gel for meloxicam.
AB  - AIM: The main objective of the current investigation was to develop
      nanostructured lipid carriers (NLC) based gel for the enhancement of transdermal
      absorption of meloxicam (MLX) to achieve local as well as systemic drug action
      without concurrent gastrointestinal toxicity. MAIN METHODS: NLC gel containing
      MLX was prepared and characterized for particle size, polydispersity, zeta
      potential, pH, rheology, entrapment efficiency, occlusion factor, and thermal
      behavior. In vitro drug release, in vitro skin permeation and deposition studies
      were carried out using Franz diffusion cells. Differential scanning calorimetry
      (DSC) and Fourier transform infrared spectroscopy (FTIR) of MLX-NLC gel treated
      stratum corneum (SC) were undertaken to get an insight into the skin permeation
      enhancement mechanism of MLX-NLC gel. Toxicity potential of the developed gel
      formulation was assessed by in vitro hemolysis and histopathological
      examinations. The rat paw edema test was performed to evaluate the anti
      inflammatory activity of MLX-NLC gel. KEY FINDINGS: MLX-NLC gel demonstrated
      sustained release and enhanced the skin permeation and deposition of meloxicam
      especially into the dermis in comparison to meloxicam gel (control). MLX-NLC had
      an impact on the barrier properties of the skin and acted via protein and lipid
      modifications in the stratum corneum. MLX-NLC gel turned out to be
      hemocompatible, non-irritant, and non toxic with significant anti-inflammatory
      activity. SIGNIFICANCE: The results suggest that NLC gel could be a promising
      carrier for the transdermal delivery of meloxicam.

PMID- 24113072
TI  - Emergence and properties of spice and bath salts: a medicinal chemistry
      perspective.
AB  - Over the past five years the number of internet sites advertising "legal highs"
      has literally exploded, as have user reports of experiences (both pleasurable and
      frightening) with these substances and the number of emergency room visits by
      users. Although the majority of these "legal highs" have been described as bath
      salts and herbal extracts, most contain neither plant derived compounds nor
      components of personal hygiene products. So-called "bath salts" largely contain
      synthetic analogs of the natural compound Khat; spice-related materials, claimed
      to be "legal marijuana," are mostly synthetic analogs of cannabinoid receptor
      ligands that were developed as research tools. This review describes the
      emergence and properties of these two groups of "legal highs" from a medicinal
      chemist's perspective. 

PMID- 24113073
TI  - Effects of N-acetyl-L-cysteine on adhesive strength between breast cancer cell
      and extracellular matrix proteins after ionizing radiation.
AB  - AIMS: To evaluate the effect of N-acetyl-L-cysteine (LNAC), a common ROS
      scavenger, on the adhesive affinity between MDA-MB-231 breast cancer cells and
      extracellular matrix (ECM) proteins after IR. MAIN METHODS: Using static cell
      adhesion assays to determine the effect of various times and duration of LNAC
      (10mM) treatment on IR (20Gy)-altered adhesive affinity between MDA-MB-231 breast
      cancer cells and ECM, especially fibronectin; using fluorescence dye carboxy- 2,7
      dichlorodihydrofluorescein diacetate to determine intracellular levels of ROS;
      using flow cytometry to determine cell surface integrin beta1; and using Western
      blot analysis to determine vimentin expression. KEY FINDINGS: Our results
      indicated that continuously treating the breast cancer cells with LNAC for 24h,
      starting immediately after IR, could inhibit IR-induced cell adhesion to ECM
      proteins at 24h post-IR. The reduction of cell adhesive affinity was correlated
      with a down-regulation of IR-induced ROS production and surface expression of
      activated integrin beta1. When the cells were pretreated for 1h, the inhibitory
      effects of LNAC were found to be either reduced or completely abrogated followed
      by 24h or 2h treatments, respectively. In addition to cell adhesion, treatment
      with LNAC inhibited IR-induced expression of vimentin, an epithelial-mesenchymal
      transition marker (EMT). SIGNIFICANCE: The benefits of administering antioxidants
      during radiation therapy have been the subject of much controversy. Our results
      suggest that if antioxidant treatment is to be combined with IR therapy, time of
      administration and treatment duration are important variables to consider.

PMID- 24113074
TI  - The antiangiogenic activity of Kushecarpin D, a novel flavonoid isolated from
      Sophora flavescens Ait.
AB  - AIMS: Kushecarpin D (KD) is a novel flavonoid isolated from the traditional
      Chinese herbal medicine Kushen (the dried root of Sophora flavescens Ait). As
      part of our continuous effort to explore Chinese traditional medicinal herbs and
      to identify novel natural anticancer products, the antiangiogenic properties of
      KD were examined in vitro using a human umbilical vein endothelial cell line
      (ECV304). MAIN METHODS: The SRB and Trypan Blue exclusion assays were used to
      evaluate the effect of KD on cell proliferation. The antiangiogenic activities of
      KD were evaluated through studies of cell migration, cell adhesion, and tube
      formation. DCFH-DA and DHE fluorescent assays were used to detect the reactive
      oxygen species (ROS) levels. Catalase activity was detected using the
      colorimetric ammonium molybdate method. Cell cycle and apoptosis were measured
      using flow cytometry and the Hoechst 33258 staining assay. KEY FINDINGS: The
      results indicated that KD showed antiangiogenic activity via inhibitory effects
      on cell proliferation, cell migration, cell adhesion, and tube formation. ROS
      levels were down-regulated and catalase activity was up-regulated after treatment
      with KD. The cell cycle was arrested at the G2/M phase, while no apoptosis was
      observed using the Hoechst 33258 staining assay or following the flow cytometric
      analysis of the sub-G1 proportion. SIGNIFICANCE: The antiangiogenic properties of
      KD, in combination with its anti-proliferative effect and ability to induce cell
      cycle arrest without inducing apoptosis, make it a good candidate for development
      as antitumor agent. However, further studies are essential to elucidate its
      mechanism of action.

PMID- 24113075
TI  - Differences in clinician-oriented outcomes among controls, copers, and chronic
      ankle instability groups.
AB  - OBJECTIVE: To compare clinician-oriented outcome measures among uninjured
      controls, copers, and chronic ankle instability (CAI) groups. DESIGN: Case
      control study. SETTING: Research Laboratory. PARTICIPANTS: Participants were 25
      active adults with unilateral CAI ([mean +/- SD] age: 23.7 +/- 4.9 years), 21
      copers ([mean +/- SD] age: 23.2 +/- 4.7 years), and 20 uninjured controls ([mean
      +/- SD] age: 21.1 +/- 2.5 years). MAIN OUTCOME MEASURES: Range of motion and
      posterior talar glide were assessed via a weight-bearing lunge and a talar glide
      test, respectively. Cutaneous sensation was measured during a Semmes-Weinstein
      Monofilament test. Dynamic balance was measured during the Star Excursion Balance
      Test (SEBT). Muscular strength was assessed during manual muscle tests of the
      dorsiflexors, plantar flexors, invertors, and evertors. RESULTS: The CAI group
      had decreased dorsiflexion range of motion relative to controls (p = 0.02). Those
      with CAI also had decreased balance during the posterior-medial reach of the SEBT
      compared to copers and controls (p < 0.01). Both copers and the CAI group had
      decreased normalized dorsiflexion strength compared to controls (p < 0.01) but
      only the CAI group had normalized plantar flexion strength deficits relative to
      controls (p = 0.04). CONCLUSIONS: Some clinician-oriented outcomes, but not all,
      can detect differences among uninjured controls, copers, and those with CAI.

PMID- 24113077
TI  - Nonstationarity of dynamic cerebral autoregulation.
AB  - Dynamic cerebral autoregulation (dCA), the transient response of cerebral blood
      flow (CBF) to rapid changes in arterial blood pressure (BP), is usually
      quantified by parameters extracted from time- or frequency-domain analysis.
      Reproducibility studies of dCA parameters and consideration of the physiological
      determinants of the dynamic BP-CBF relationship provide strong indications that
      dCA is a nonstationary process. As a consequence, new analytical approaches are
      needed to estimate dCA parameters with greater temporal resolution thus allowing
      its longitudinal patterns of variability to be assessed in health and disease
      states. Techniques proposed for this task include ARMA models with moving
      windows, recursive least-squares, Laguerre-Volterra networks, wavelet phase
      synchronisation, and multimodal pressure-flow analysis. Initial results with
      these techniques have revealed the influence of some key determinants of dCA
      nonstationarity, such as PaCO2, as well as their ability to reflect dCA
      impairment in different clinical conditions. One key priority for future work is
      the development and validation of multivariate time-varying techniques to
      minimise the influence to the many co-variates which contribute to dCA
      nonstationarity. 

PMID- 24113076
TI  - Optimizing the ingredients for imagery-based interpretation bias modification for
      depressed mood: is self-generation more effective than imagination alone?
AB  - Negative interpretation is thought to be crucial in the development and
      maintenance of depression. Recently developed cognitive bias modification
      paradigms, intending to change these biases towards a more optimistic
      interpretation tendency (CBM-I), seem to offer new promising implications for
      cognitive therapy innovation. This study aimed to increase our knowledge of the
      underlying mechanisms of action of imagery-based CBM-I in the context of
      depressed mood. We therefore compared the efficacy of CBM-I requiring
      participants to imagine standardized positive resolutions to a novel, more active
      training version that required participants to generate the positive
      interpretations themselves. Fifty-four participants were randomly allocated to
      (1) standardized CBM-I, (2) self-generation CBM-I or (3) a control group. Outcome
      measures included self-report mood measures and a depression-related
      interpretation bias measure. Both positive training variants significantly
      increased the tendency to interpret fresh ambiguous material in an optimistic
      manner. However, only the standardized imagery CBM-I paradigm positively
      influenced mood. 

PMID- 24113078
TI  - Depleted TGF-beta1 levels in end stage renal disease patients from North India.
AB  - End stage renal disease is a clinical state that extends from chronic renal
      failure and is marked by an irreversible loss of renal function. TGF-beta1
      mediated renal fibrosis is a common pathology implicated in this form of kidney
      disease. In this study circulating protein and mRNA levels of TGF-beta1 cytokine
      were investigated among ESRD patients and respective controls from North India.
      Physician diagnosed 192 ESRD patients, on hemodialysis, and 130 normal controls
      participated in the present study. TGF-beta1 circulating levels were measured by
      ELISA and its expression was quantified using competitive-PCR. Mean TGF-beta1
      protein levels were 2.7-fold lower in ESRD patients as compared to normal
      controls (p<0.001). Additionally, TGF-beta1 mRNA transcripts of this cytokine
      were also significantly lower in the diseased population compared to controls
      (p<0.001). These results imply that TGF-beta1 has not played its anticipated pro
      fibrotic role and anti-inflammatory function in the studied population. 

PMID- 24113079
TI  - Two mitochondrial genes under episodic positive selection in subterranean
      octodontoid rodents.
AB  - Tuco-tucos (Ctenomys) and related coruros (Spalacopus) are South American
      subterranean rodents. An energetically demanding lifestyle within the hypoxic,
      underground atmosphere may change the selective regime on oxidative
      phosphorylation. We examined whether weak and/or episodic positive directional
      selection affected the evolution of two mitochondrial genes (COX2, CytB), in a
      background of purifying selection in these lineages. We estimated rates of
      synonymous (dS) and non-synonymous (dN) substitutions and found: 1) significantly
      higher dN/dS ratio in subterranean groups relative to non-subterranean related
      species, and 2) two codons in each gene under episodic selection: 94 and 277 of
      COX2 and 269 and 307 of CytB. 

PMID- 24113081
TI  - MK-801-induced and scopolamine-induced hyperactivity in rats neonatally treated
      chronically with MK-801.
AB  - This study investigated the effects of chronic neonatal blockade of N-methyl-D
      aspartate (NMDA) receptors on NMDA and muscarinic acetylcholine receptor-mediated
      neurotransmission in adulthood. Rats neonatally treated chronically with MK
      801/saline were tested for 40 min, at the age of 14-16 weeks, for locomotor
      activity in an open field immediately after acute administration of MK-801 (0.2
      mg/kg) or scopolamine (0.4-2.0 mg/kg). Rats neonatally treated with MK-801 showed
      significantly higher locomotor activity than those treated with saline. Acute MK
      801 administration caused hyperlocomotion regardless of neonatal treatment, but
      the effect was more potent in rats neonatally treated with MK-801. In contrast,
      acute scopolamine administration did not cause hyperlocomotion in rats neonatally
      treated with saline, but significantly increased locomotion in those neonatally
      treated with MK-801. The results suggest that chronic neonatal NMDA receptor
      blockade causes changes in glutamatergic and cholinergic transmission in
      adulthood long after the cessation of treatment. 

PMID- 24113080
TI  - The dopamine D2 antagonist eticlopride accelerates extinction and delays
      reacquisition of food self-administration in rats.
AB  - Dopamine receptors are implicated in the reinforcing effects of food and drug
      reinforcement. The purpose of this study was to evaluate whether blocking D2
      dopamine receptors during extinction (secondary reinforcement) would affect
      reacquisition of responding for food pellets (primary reinforcement). Food
      restricted rats self-administered (fixed-ratio 1) food pellets in 1-h daily
      sessions for 7 days. For the next 7 days rats responded in extinction conditions.
      Before each extinction session rats were injected with saline or the dopamine D2
      antagonist eticlopride (0.03 mg/kg, subcutaneously). After the extinction phase,
      rats were allowed to reacquire food pellet self-administration in seven daily
      sessions, and received saline or eticlopride before each session. Four treatment
      groups were represented: saline extinction, saline reacquisition; eticlopride
      extinction, saline reacquisition; saline extinction, eticlopride reacquisition;
      and eticlopride extinction, eticlopride reacquisition. Locomotor activity did not
      differ between eticlopride-treated and saline-treated rats throughout the study.
      Extinction was accelerated in eticlopride-treated rats. Eticlopride also delayed
      reacquisition of food self-administration compared with saline-treated rats. Rats
      administered eticlopride during extinction showed delayed reacquisition and a
      decreased response rate for food during the reacquisition phase. Indirectly
      reducing the value of a reinforcer in this way may provide a novel approach for
      reducing addiction-related food or drug self-administration behaviors. 

PMID- 24113082
TI  - Prevalence and genetic diversity of arginine catabolic mobile element (ACME) in
      clinical isolates of coagulase-negative staphylococci: identification of ACME
      type I variants in Staphylococcus epidermidis.
AB  - Arginine catabolic mobile element (ACME), a genomic island consisting of the arc
      and/or opp3 gene clusters found in staphylococcal species, is related to
      increased bacterial adaptability to hosts. Staphylococcus epidermidis is
      considered a major ACME reservoir; however, prevalence and genetic diversity of
      ACME in coagulase-negative staphylococci (CNS) have not yet been well
      characterized for clinical isolates in Japan. A total of 271 clinical isolates of
      CNS in a Japanese hospital were investigated for the presence and genotype of
      ACME and SCCmec. The prevalence of ACME-arcA was significantly higher (p<0.001)
      in S. epidermidis (45.8%) than in other CNS species (3.7%). ACME in S.
      epidermidis isolates (n=87) were differentiated into type I (n=33), variant forms
      of type I (DeltaI, n=26) newly identified in this study, type II (n=6), and type
      DeltaII (n=19). ACME-type DeltaI, which were further classified into three
      subtypes, lacked some genetic components between the arc and opp3 clusters in
      archetypal type I, whereas the arc and opp3 clusters were intact. The arc cluster
      exhibited high sequence identity (95.8-100%) to that of type I ACME; in contrast,
      the opp3 cluster was highly diverse, and showed relatively lower identities (94.8
      98.7%) to the identical regions in type I ACME. Twenty-one isolates of DeltaI
      ACME-carrying S. epidermidis possessed SCCmec IVa and belonged to ST5 (clonal
      complex 2). Phylogenetic analysis revealed that isolates harboring ACME DeltaI in
      this study clustered with previously reported S. epidermidis strains with other
      lineges, suggesting that S. epidermidis originally had some genetic variations in
      the opp3 cluster. In summary, ACME type DeltaI, a truncated variant of ACME-I,
      was first identified in S. epidermidis, and revealed to be prevalent in ST5 MRSE
      clinical isolates with SCCmec IVa. 

PMID- 24113083
TI  - Genetic variability of human respiratory syncytial virus in Pune, Western India.
AB  - Human respiratory syncytial virus (RSV) is one of the most important respiratory
      viruses causing acute respiratory tract infections amongst children. Based on
      genotyping of the attachment glycoprotein (G) gene, it is divided into two
      groups, RSV-A and RSV-B. Infection with one group does not confer immunity
      against the other and children infected with one antigenic group are more likely
      to be reinfected with the heterologous group. We tested 854 samples of patients
      with influenza like illness (ILI)/severe respiratory illness (SARI) during the
      period 2009-2012 for RSV using a conventional multiplex RT-PCR and found 159
      (18.61%) samples to be positive for RSV of which 130 (15.22%) were positive for
      RSV-B and 29 (3.39%) for RSV-A suggesting that RSV-B was the predominant group
      circulating in Western India during the study period. Seasonal RSV outbreaks were
      observed in the monsoon and winter months. RSV was more prevalent amongst
      children in the 0-24 month age group (21.53%) in comparison to children in the 24
      60 month age group (13.01%). Phylogenetic analysis using the G gene of 27
      representative RSV-A positive samples revealed that all sequences belonged to the
      NA1 genotype. Of these, 5 sequences exhibited the novel 72 nucleotide duplication
      in the C-terminal of the G gene first reported from Ontario, Canada and clustered
      in the newly designated ON1 genotype. Also, 32 of the 33 RSV-B sequences
      exhibited the 60 nucleotide duplication associated with genotype BA and
      phylogenetic analysis showed that these sequences belonged to the genotype BA9
      and BA12. We also found one RSV-B sequence belonging to genotype GB2, which has
      not been previously reported in India.

PMID- 24113084
TI  - Health education literacy in patients with chronic musculoskeletal diseases:
      development of a new questionnaire and sociodemographic predictors.
AB  - It was our aim to develop a questionnaire for patients with chronic
      musculoskeletal diseases to self-report their health education literacy, to
      analyse the psychometric properties of the instrument and to test hypotheses
      concerning sociodemographic predictors of health education literacy. A total of
      577 patients with chronic back pain or osteoarthritis who underwent inpatient
      rehabilitation were surveyed. The resulting 'HELP questionnaire' (health
      education literacy of patients with chronic musculoskeletal diseases) consists of
      18 items and three scales (comprehension of medical information, applying medical
      information, communicative competence in provider interactions). The instrument's
      psychometric properties are good (Cronbach's alpha between 0.88 and 0.95,
      unidimensionality and Rasch model fit established). Our sample's average level of
      self-reported health education literacy is quite high. However, 20-30% of the
      patients admitted to having difficulty understanding important aspects of health
      education programmes (i.e. comprehending what medical information means in
      relation to their disease). The variance explained by sociodemographic and basic
      medical variables is small (4-8%). Greater effort is required to make health
      education programmes easier to understand. There is a need for more research on
      interindividual variability of complex aspects of health literacy. 

PMID- 24113085
TI  - Electronic sensitization of the response to C2H5OH of p-type NiO nanofibers by Fe
      doping.
AB  - Pure and 0.18-13.2 at.% Fe-doped NiO nanofibers were prepared by electrospinning
      and their gas sensing characteristics and microstructural evolution were
      investigated. The responses ((Rg - Ra)/Ra, where Rg is the resistance in gas and
      Ra is the resistance in air) to 5 ppm C2H5OH, toluene, benzene, p-xylene, HCHO,
      CO, H2, and NH3 at 350-500  degrees  C were significantly enhanced by Fe doping
      of the NiO nanofibers, while the responses of pure NiO nanofibers to all the
      analyte gases were very low ((Rg - Ra)/Ra = 0.07-0.78). In particular, the
      response to 100 ppm C2H5OH was enhanced up to 217.86 times by doping of NiO
      nanofibers with 3.04 at.% Fe. The variation in the gas response was closely
      dependent upon changes in the base resistance of the sensors in air. The enhanced
      gas response of Fe-doped NiO nanofibers was explained in relation to electronic
      sensitization, that is, the increase in the chemoresistive variation due to the
      decrease in the hole concentration induced by Fe doping.

PMID- 24113086
TI  - Pivotal role of tissue plasminogen activator in the mechanism of action of
      electroconvulsive therapy.
AB  - Electroconvulsive therapy is an important treatment option for major depressive
      disorders, acute mania, mood disorders with psychotic features, and catatonia.
      Several hypotheses have been proposed as electroconvulsive therapy's mechanism of
      action. Our hypothesis involves many converging pathways facilitated by increased
      synthesis and release of tissue-plasminogen activator. Human and animal
      experiments have shown that tissue-plasminogen activator participates in many
      mechanisms of action of electroconvulsive therapy or its animal variant,
      electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor
      mediated signaling, activation of both brain-derived neurotrophic factor and
      vascular endothelial growth factor, increased bioavailability of zinc, purinergic
      release, and increased mobility of dendritic spines. As a result, tissue
      plasminogen activator helps promote neurogenesis in limbic structures, modulates
      synaptic transmission and plasticity, improves cognitive function, and mediates
      antidepressant effects. Notably, electroconvulsive therapy seems to influence
      tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus
      increases the expression of glutamate decarboxylase 65 isoform in gamma
      aminobutyric acid-releasing neurons, which enhances the release of tissue
      plasminogen activator, and the expression of p11, a protein involved in
      plasminogen and tissue-plasminogen activator assembling. This paper reviews how
      electroconvulsive therapy correlates with tissue-plasminogen activator. We
      suggest that interventions aiming at increasing tissue-plasminogen activator
      levels or its bioavailability - such as daily aerobic exercises together with a
      carbohydrate-restricted diet, or normalization of homocysteine levels - be
      evaluated in controlled studies assessing response and remission duration in
      patients who undergo electroconvulsive therapy. 

PMID- 24113088
TI  - Salient collinear grouping diminishes local salience in visual search: an eye
      movement study.
AB  - Our eyes and attention are easily attracted to salient items in search displays.
      When a target is spatially overlapped with a salient distractor (overlapping
      target), it is usually detected more easily than when it is not (nonoverlapping
      target). Jingling and Tseng (2013), however, found that a salient distractor
      impaired visual search when the distractor was comprised of more than nine bars
      collinearly aligned to each other. In this study, we examined whether this search
      impairment is due to reduction of salience on overlapping targets. We used the
      short-latency saccades as an index for perceptual salience. Results showed that a
      long collinear distractor decreases perceptual salience of local overlapping
      targets in comparison to nonoverlapping targets, reflected by a smaller
      proportion of the short-latency saccades. Meanwhile, a salient noncollinear
      distractor increases salience of overlapping targets. Our results led us to
      conclude that a long collinear distractor diminishes the perceptual salience of
      the target, a factor which poses a counter-intuitive condition in which a target
      on a salient region becomes less salient. We discuss the possible causes for our
      findings, including crowding, the global precedence effect, and the filling-in of
      a collinear contour. 

PMID- 24113087
TI  - Real-time recording and classification of eye movements in an immersive virtual
      environment.
AB  - Despite the growing popularity of virtual reality environments, few laboratories
      are equipped to investigate eye movements within these environments. This primer
      is intended to reduce the time and effort required to incorporate eye-tracking
      equipment into a virtual reality environment. We discuss issues related to the
      initial startup and provide algorithms necessary for basic analysis. Algorithms
      are provided for the calculation of gaze angle within a virtual world using a
      monocular eye-tracker in a three-dimensional environment. In addition, we provide
      algorithms for the calculation of the angular distance between the gaze and a
      relevant virtual object and for the identification of fixations, saccades, and
      pursuit eye movements. Finally, we provide tools that temporally synchronize gaze
      data and the visual stimulus and enable real-time assembly of a video-based
      record of the experiment using the Quicktime MOV format, available at
      http://sourceforge.net/p/utdvrlibraries/. This record contains the visual
      stimulus, the gaze cursor, and associated numerical data and can be used for data
      exportation, visual inspection, and validation of calculated gaze movements. 

PMID- 24113089
TI  - A simple protocol for producing high-titer lentivirus.

PMID- 24113090
TI  - The Zalpha domain of fish PKZ converts DNA hairpin with d(GC)(n) inserts to Z
      conformation.
AB  - PKZ, protein kinase containing Z-DNA domains, is a novel member of the vertebrate
      eIF2alpha kinase family. Containing a catalytic domain in C-terminus and two Z
      DNA binding domains (Zalpha1 and Zalpha2) in N-terminus, PKZ can be activated
      through the binding of Zalpha to Z-DNA. However, the regulatory function of PKZ
      Zalpha remains to be established. Here, to understand the impact of PKZ Zalpha on
      DNA conformational transition, wild-type Zalpha1Zalpha2 and 11 mutant proteins
      were expressed and purified. At the same time, several different lengths of DNA
      hairpins-d(GC)nT4(GC)n (n = 2-6) and an RNA hairpin-r(GC)6T4(GC)6 were
      synthesized. The effects of Zalpha1Zalpha2 and mutant proteins on the
      conformation of these synthetic DNA or RNA hairpins were investigated by using
      circular dichroism spectrum and gel mobility shift assays. The results showed
      that DNA hairpins retained a conventional B-DNA conformation in the absence of
      Zalpha1Zalpha2, while some of the DNA hairpins (n>=3) were converted to Z
      conformation under Zalpha1Zalpha2 induction. The tendency was proportionally
      associated with the increasing amount of GC repeat. In comparison with
      Zalpha1Zalpha2, Zalpha1Zalpha1 rather than Zalpha2Zalpha2 displayed a higher
      ability in converting d(GC)6T4(GC)6 from B- to Z-DNA. These results demonstrated
      that Zalpha1 sub-domain played a more essential role in the process of B-Z
      conformational transition than Zalpha2 sub-domain did. Mutant proteins (K34A,
      N38A, R39A, Y42A, P57A, P58A, and W60A) could not convert d(GC)6T4(GC)6 into Z
      DNA, whereas S35A or K56A retained some partial activities. Interestingly,
      Zalpha1Zalpha2 was also able to induce r(GC)6T4(GC)6 RNA from A-conformation to Z
      conformation under appropriate conditions. 

PMID- 24113028
TI  - Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized,
      controlled trial.
AB  - Cost-effective strategies to maintain healthy active lifestyle in aging
      populations are required to address the global burden of age-related diseases.
      ASPREE will examine whether the potential primary prevention benefits of low dose
      aspirin outweigh the risks in older healthy individuals. Our primary hypothesis
      is that daily oral 100 mg enteric-coated aspirin will extend a composite primary
      endpoint termed 'disability-free life' including onset of dementia, total
      mortality, or persistent disability in at least one of the Katz Activities of
      Daily Living in 19,000 healthy participants aged 65 years and above ('US
      minorities') and 70 years and above (non-'US minorities'). ASPREE is a double
      blind, randomized, placebo-controlled trial of oral 100mg enteric-coated acetyl
      salicylic acid (ASA) or matching placebo being conducted in Australian and US
      community settings on individuals free of dementia, disability and cardiovascular
      disease (CVD) events. Secondary endpoints are all-cause and cause specific
      mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer
      (excluding non-melanoma skin cancer), dementia, mild cognitive impairment,
      depression, physical disability, and clinically significant bleeding. To 20
      September 2013 14,383 participants have been recruited. Recruitment and study
      completion are anticipated in July 2014 and December 2018 respectively. In
      contrast to other aspirin trials that have largely focused on cardiovascular
      endpoints, ASPREE has a unique composite primary endpoint to better capture the
      overall risk and benefit of aspirin to extend healthy independent lifespan in
      older adults in the US and Australia.

PMID- 24113091
TI  - Selection of reference genes for quantitative gene expression studies in the
      house fly (Musca domestica L.) using reverse transcription quantitative real-time
      PCR.

PMID- 24113092
TI  - A probabilistic model estimating oil spill clean-up costs--a case study for the
      Gulf of Finland.
AB  - Existing models estimating oil spill costs at sea are based on data from the
      past, and they usually lack a systematic approach. This make them passive, and
      limits their ability to forecast the effect of the changes in the oil combating
      fleet or location of a spill on the oil spill costs. In this paper we make an
      attempt towards the development of a probabilistic and systematic model
      estimating the costs of clean-up operations for the Gulf of Finland. For this
      purpose we utilize expert knowledge along with the available data and information
      from literature. Then, the obtained information is combined into a framework with
      the use of a Bayesian Belief Networks. Due to lack of data, we validate the model
      by comparing its results with existing models, with which we found good
      agreement. We anticipate that the presented model can contribute to the cost
      effective oil-combating fleet optimization for the Gulf of Finland. It can also
      facilitate the accident consequences estimation in the framework of formal safety
      assessment (FSA). 

PMID- 24113093
TI  - [Building the Chinese system for food safety based on the frame of risk
      assessment].

PMID- 24113094
TI  - [The pollution of fine particulate matter(PM2.5) and population health during the
      smog period].

PMID- 24113096
TI  - [Etiology of acute respiratory tract infection in hospitalized children in Suzhou
      from 2005 to 2011].
AB  - OBJECTIVE: To elucidate the etiology of acute respiratory tract infection (ARI)
      in hospitalized children in Suzhou from 2005 to 2011. METHODS: A total of 10 243
      hospitalized children with ARI in Children's Hospital Affiliated to Soochow
      University from September 2005 to October 2011 were enrolled in the study. The
      clinical information was collected; and the nasopharyngeal aspiration fluid and
      serum samples were sent for multi-pathogen detection. Respiratory syncytial virus
      (RSV), influenza virus type A and B (IV-A, IV-B), parainfluenza virus type 1-3
      (PIV-1-PIV-3) and adenovirus (ADV) were detected by direct immunofluorescence
      assay. Human bocavirus (HBoV), mycoplasma pneumoniae (MP) and chlamydia
      pneumoniae (CP) were detected by fluorescent quantitative PCR while human
      metapneumovirus (hMPV) was detected by reverse transcription PCR (RT-PCR). Sputum
      culture was applied to detect bacterial infection and quantitative ELISA was
      adopted to detect the specific antibodies of MP and CP. The results of the above
      detections were analyzed, and thereby to explore the prevalent pathogens among
      different aging children and the seasonal distribution and characteristics of the
      disease. RESULTS: At least one type of pathogen was detected in 5871 out of 10
      243 hospitalized children and the overall positive rate was 57.32%; including
      3326 virus samples with positive rate at 32.47% (3326/10 243), 2870 bacteria
      samples with positive rate at 28.02% (2870/10 243) and 2759 atypical pathogen
      samples,with positive rate at 26.94% (2759/10 243). MP was the most common
      pathogen,whose detected rate was 25.74% (2637/10 243). The median age of children
      with RSV (6 months) or PIV-3(8 months) infection was younger than the median age
      of all hospitalized children (12 months) (chi(2) = 380.992, 34.826, P < 0.05).
      While the median age of children with ADV (42 months), HBoV (14 months) or IV-A
      (24 months) infection was older than it of all hospitalized children (chi(2) =
      83.583, 13.169, 18.012, P < 0.05). The median age of children with MP (30
      months),streptococcus pneumoniae (17 months) or haemophilus parainfluenzae (21
      months) infection was older than it of all hospitalized children (chi(2) =
      728.299, 60.463, 8.803, P < 0.05). The detected rate of RSV in the groups of
      children aging less than 6 months, 7-12 months, 2-3 years, 4-5 years and over 6
      years was separately 25.59% (840/3283), 17.05% (333/1953), 11.85% (310/2615),
      6.68% (90/1347), and 2.87% (30/1045); which decreased while the age grew (chi(2)
      = 178.46, P < 0.01). Conversely, the positive rate of MP increased with the age
      growing (chi(2) = 379.21, P < 0.01). The rate in the above groups was 8.25%
      (271/3283), 19.46% (380/1953), 33.00% (863/2615), 41.43% (558/1347), 54.07%
      (565/1045), respectively. RSV and IV-A were prevalent in winter, whose detected
      rates were 35.73% (941/2634) and 4.44% (117/2634) respectively.hMPV infection was
      common in spring, with the detected rate at 10.55% (278/2634); while HBoV
      infection was common in summer and autumn, with the positive rate at 9.99%
      (149/1491) and 9.71% (98/1009). MP and CP were frequently detected in summer, up
      to 31.27% (819/2619) and 10.07% (43/427) respectively. RSV was the most common
      pathogen in bronchiolitis (33.27% (866/2603)) and MP was the most common pathogen
      in bronchopneumonia (26.05% (1152/4422)) and lober pneumonia (52.25% (267/511)).
      CONCLUSION: MP and RSV were the most common pathogens in respiratory tract
      infection in hospitalized children. The novel virus included hMPV and HBoV, which
      also played an important role in ARI. Different pathogens were prevalent in
      different ages; with respective seasonal distribution and characteristics.

PMID- 24113095
TI  - [The application of suspension array technology in multiplex detection of typical
      environmental chemical pollutants].

PMID- 24113097
TI  - [Analysis on coverage rate of primary immunization of measles vaccine among
      migrant children in Yiwu, Zhejiang province from 2007 to 2010].
AB  - OBJECTIVE: To investigate the coverage rate of primary immunization of measles
      containing vaccine (MCV1) among migrant children in Yiwu,Zhejiang province.
      METHODS: Household cluster sampling survey and probability proportion to size
      sampling method were adopted. A total of 967 migrant children born from 1st July
      2007 to 1st July 2010 and their caregivers were selected as target population.
      Standard face-to-face interviews were conducted to investigate the subjects'
      knowledge, attitude, practice (KAP) of immunization, MCV1 vaccination and
      determinants. Multi-variable weighted average score method was adopted to
      evaluate the result of our survey on KAP. Kaplan-Meier analysis was adopted to
      assess the coverage of MCV1 and Cox regression analysis was adopted to explore
      the influencing factors associated with the coverage of MCV1. RESULTS: Out of the
      967 children, 104 were born in 2007, accounting for 10.8%; 301 were born in 2008,
      accounting for 31.1%; 343 were born in 2009, accounting for 35.5% and 219 were
      born in 2010, accounting for 22.6%. Among the surveyed caregivers, 71.9%
      (695/967) were mothers and 90.2% (872/976) were migrant from other provinces.
      According to the result of survey on KAP among caregivers, 56.2% (543/967) scored
      >= 4 points on knowledge, 75.8% (734/967) scored >= 4 points on attitude and
      48.7% (471/967) scored >= 4 points on behavior. 86.6% (838/967) of surveyed
      caregivers' education levels were under junior middle school.85.9% (831/967) of
      the migrant children were born in hospitals.36.3% (351/967) of the surveyed
      families' household income were under 2000 yuan per month.32.7% (316/967) of
      surveyed caregivers waited less than 15 min for immunization for each time.
      Coverage rate of MCV1 was 85.9% (831/967; 95%CI: 83.7%-88.1%). The timely
      coverage rates at 8 months, 12 months, and 24 months were 58.8% (569/967; 95%CI:
      55.5%-62.1%), 88.2% (853/967; 95%CI: 86.0%-90.4%) and 98.6% (953/967; 95%CI:
      97.8%-99.4%), respectively. The average age of MCV1 immunization for each birth
      cohort between 2007 and 2010 were 10.4, 10.1, 10.1 and 9.3 month, respectively;
      without statistical significance (chi(2) = 0.722, P = 0.398). According to the
      analysis by Cox regression, the caregivers aged <= 25 years (24.3% (235/967), RR
      = 1.520 (95%CI: 1.280-1.800)), the caregivers' education level above college
      (2.8% (27/967), RR = 3.841 (95%CI: 2.287-6.451)), delivered in county-level
      hospital (49.4% (478/967), RR = 6.048 (95%CI: 4.311-8.485)), household income >
      4000 yuan per month (21.7% (210/967), RR = 1.366 (95%CI:1.163-1.604)), the
      average score of attitude towards immunization >= 4 points (75.9%(734/967), RR =
      2.613 (95%CI: 1.026-6.655)), the average waiting time for each vaccination <= 15
      min (32.7% (316/967), RR = 2.116 (95%CI: 1.341-3.339)) were the important factors
      to improve the timely immunization coverage rate of MCV1 among migrant children.
      CONCLUSION: The coverage of MCV1 were obviously delayed among migrant children in
      Yiwu, Zhejiang province. We suggest that the investigation of migrant children
      should be strengthened and remind or recall mechanism for immunization should be
      established. Increasing the open days for immunization clinics and reducing the
      waiting time for vaccination could also improve the coverage and timeliness of
      the MCV vaccination.

PMID- 24113098
TI  - [The infection status of Leptospira in rodents on the Heixiazi island of
      Heilongjiang province, China,in 2011].
AB  - OBJECTIVE: To study the infection status of Leptospira in rodents on Heixiazi
      island Heilongjiang province in 2011. METHODS: A total of 356 rodents were
      captured by night trap on the Heixiazi island from April to October 2011. The
      kidney tissue samples were collected by asepsis operation and the genomic DNA
      were extracted from them. Leptospira strains were confirmed by polymerase chain
      reaction(PCR) amplification of the 482 bp 23 S rDNA gene. Fifteen PCR products
      selected by the month were purified and sequenced by the methods of Sanger
      dideoxy, the sequences then compared with other Leptospira strains in Genebank,
      and phylogenetic analyses were drafted by software Mega 4.0. RESULTS: Among 356
      rodents, the dominant species were Clethrionomys rutilus (39.3%, 140/356) and
      Apodemus agrarius (36.0%, 128/356). The infection rate of Leptospira was 11.0%,
      with 39 rodent samples detected positive. All the rodent species were infected
      except for Rattus norvegicus. The infection rate was 9.4% (12/128) in Apodemus
      agrarius, 12.9%(18/140) in Clethrionomys rutilus, 10.8%(7/65) in Microtus fortis
      Buchner. No significant difference was found between the infection rate and the
      species of rodents by chi square test(chi(2) = 1.92, P > 0.05). Among months, the
      infection rate was 5.6% (4/72) in May, 8.8% (5/57) in June, 12.8% (5/39) in July,
      9.8% (5/51) in August, 33.3% (11/33) in September, 22.5% (9/40) in October,but no
      infection in April. There was significant difference in infection in different
      months (chi(2) = 32.92, P < 0.05). All the Leptospira in rodents on the Heixiazi
      island were in the same phylogenetic branch with a high similarity of 97.1%
      99.6%, close with the Australia strain U90865 by the similarity above 96.3%.
      CONCLUSION: Leptospira is probably prevalent in rodents on the Heixiazi island,
      and the phylogene of the strains were similar. The infection rate in rodents was
      significantly different in months but not in hosts.

PMID- 24113099
TI  - [Genetic evolution analysis of matrix protein 2 gene of avian influenza H5N1
      viruses from boundary of Yunnan province].
AB  - OBJECTIVE: To elucidate the variation in characterizations and genetic evolution
      of the matrix protein 2 or ion channel protein(M2) genes of avian influenza
      subtype H5N1 viruses in the boundary region of Yunnan province from 2008 to 2012.
      METHODS: A total of swab samples were collected from foreign poultry such as the
      junction between Yunnan and Vietnam, Laos,myanmar and wild birds in boundary
      region of Yunnan province from 2008 to 2012 and screened by H5N1 subtype-specific
      multiplex RT-PCR. The M genes of H5N1 virus from the positive samples were
      amplified by RT-PCR and cloned into pMD18-T vectors for sequencing. The alignment
      and phylogenetic analysis of M2 genes were performed with sequences of the known
      reference strains. RESULTS: A total of 71 positive samples were found out of 1240
      samples and the positive rate was 5.72%. A total of 14 different M2 sequences
      were obtained from 30 positive samples and were divided into 3 distinct clades or
      sub-clades(1.2.1, 1.2.2 and 2) by phylogenetic analysis, 5, 7 and 2,
      respectively. The M2 genes and Hemagglutinin(HA) genes of H5N1 viruses from the
      boundary region of Yunnan province had showed different relationship of genetic
      evolution. The substitution or mutation of key amino acids sites had been found
      among the domains of epitope, adamantane-resistance, and poultry or human
      original viral strains. CONCLUSION: The M2 genes of H5N1 subtype viruses in
      boundary region of Yunnan province from 2008 to 2012 showed genetic divergence
      and the virus of clade 1.2.2 had become dominant epidemic strain in this region.

PMID- 24113100
TI  - [Epidemiological survey on the hepatitis C virus and its genotyping analysis in
      Henan province in 2012].
AB  - OBJECTIVE: To investigate the prevalence and distribution of hepatitis C virus
      (HCV) genotypes in Henan province in 2012. METHODS: A total of 32 203 permanent
      residents (1 to 74 years old) in Henan were recruited using multi-stage random
      samping method from March to June 2012. All participants were asked to complete a
      questionnaire to collect demographic information, past medical history and the
      exposure history of risk factors. A blood sample of 5 ml was collected at the
      same time. The condition of anti-HCV and HCV RNA was determined through the ELISA
      test and nested RT-PCR. HCV RNA positive samples were further subject to the
      nonstructural protein 5 region (NS5B) gene amplification and sequencing. The
      sequence was amplified for the phylogenetic tree and genetic analysis. The
      differences of the positive rate of anti-HCV and HCV RNA and the HCV genetic
      subtype distribution in different respondents'characteristics were analyzed.
      RESULTS: Among 32 203 subjects, the overall positive rate of anti-HCV and HCV RNA
      were 0.48% (153/32 203) and 0.24% (78/32 203), in which men were 0.42% (65/15
      634), and 0.23% (36/15 634), and women were 0.53% (88/16 569) and 0.25% (42/16
      596). The differences between men and women were not statistically significant
      (chi(2) values were 2.26, 0.18, respectively, both P values > 0.05). The results
      of NS5B genotyping and molecular evolution analysis showed that there were six
      subtypes in the 71 HCV RNA positive samples.In those six subtypes, the proportion
      of genotypes 1b, 6a, 3a, 2a, 3b and 1a were 56.3% (40/71), 19.7% (14/71), 11.3%
      (8/71), 8.5% (6/71), 2.8% (2/71) and 1.4% (1/71), respectively. The HCV genetic
      subtypes of infestor were mainly present with two branches of 1b and 6a, and the
      two subtypes Bootstrap values were 0.95. CONCLUSION: The prevalence of HCV
      infection was high in Henan. The major HCV genotypes in patients with HCV
      infection were 1b and 6a.

PMID- 24113101
TI  - [Interaction effects of breastfeeding and passive smoking on asthma and asthma
      related symptoms among children].
AB  - OBJECTIVE: To evaluate the interaction effects of breastfeeding and passive
      smoking on asthma and asthma related symptoms among children. METHODS: Using a
      cluster random sampling method, 2 elementary schools and 1 kindergarten were
      randomly selected from 7 cities of Liaoning province. The resulting 25 elementary
      schools and 50 kindergartens were included, and 31 049 children from the selected
      schools living up to 2 years were recruited in this survey. The information about
      the children's type of feeding up, living environment, passive smoking exposure,
      respiratory diseases and symptoms were collected. The interaction effects of
      breastfeeding and passive smoking on asthma and asthma related symptoms
      (persistent cough,persistent phlegm, current wheeze and allergic rhinitis) were
      evaluated with Glimmix procedure. RESULTS: There were 31 049 children involved in
      this investigation. The age was (8.32 +/- 2.75) years old. There were 23 987
      (77.26%) children with breastfeeding and 11 820 (38.07%) children with passive
      smoking. The prevalence of asthma and allergic rhinitis were 6.22%(1491/23 987),
      4.67%(1120/23 987) in children with breastfeeding, and were 7.70%(544/7062),
      5.48%(387/7062) in children without breastfeeding,compared to the children
      without breastfeeding, the children with breastfeeding had lower risk of
      asthma(OR = 0.79, 95%CI:0.72-0.88) and allergic rhinitis(OR = 0.85, 95%CI:0.75
      0.95); The prevalence of current wheeze was 7.89%(929/11 770) in children with
      father smoking, and was 5.37%(1036/19 279) in children without father smoking,
      compared to the children without father smoking, the children with father smoking
      increased the risk of current wheeze(OR = 1.51, 95%CI:1.38-1.65). The prevalence
      of persistent cough was 18.96%(51/269) in children with mother smoking, and was
      9.51%(2926/30 780) in children without mother smoking,compared to the children
      without mother smoking, the children with mother smoking increased the risk of
      persistent cough(OR = 2.23, 95%CI:1.64-3.03). The prevalence of persistent phlegm
      was 5.69%(871/5316) in children with anyone smoking, and was 3.50%(550/15 733) in
      children without anyone smoking, compared to the children without anyone smoking,
      the children with anyone smoking increased the risk of persistent phlegm(OR =
      1.67, 95%CI:1.49-1.86).Glimmix procedure analysis showed there was a significant
      interaction effects between breastfeeding and passive smoking. The estimated OR
      for father smoking among breastfeeding children were consistently lower than
      those among non-breastfeeding children for asthma. The estimated OR for mother
      smoking among breastfeeding children were consistently lower than those among non
      breastfeeding children for allergic rhinitis. The estimated OR for anyone smoking
      among breastfeeding children were consistently lower than those among non
      breastfeeding children for asthma and allergic rhinitis(all P values < 0.05).
      CONCLUSION: Breastfeeding decreases the detrimental effects of passive smoking on
      asthma and asthma related symptoms in children.

PMID- 24113102
TI  - [Association between mortality rate of hepatic carcinoma and the distance from
      Suihe River in Lingbi county, Anhui province].
AB  - OBJECTIVE: To explore the association between mortality rate of hepatic carcinoma
      and the distance from Suihe River in Lingbi county, Suzhou, Anhui province.
      METHODS: Using the disease mapping and spatial statistical analysis techniques,we
      described the spatial distributions of the mortality rate of hepatic carcinoma
      from 2005 to 2010 in Lingbi county. Taking the distance between villages and
      polluted rivers as proxy variable of environmental exposure, mortality rate of
      hepatic carcinoma in each village as dependant variable, and using the Glimmix
      model and Bayesian spatial model (BYM) to undertake the univariate and
      multivariate analysis, we investigatived the association between mortality rate
      of hepatic carcinoma and the water pollution of Suihe River in Lingbi county.
      RESULTS: Obvious clustering of high mortality rate of hepatic carcinoma along the
      polluted river was observed in Lingbi county. Results of Glimmix model showed
      that whether spatial autocorrelation was considered or not, closer to the
      polluted river has higher mortality rate of hepatic carcinoma. Results of
      univariate analysis of the BYM model showed that, compared with the villages far
      from the polluted river more than 12 km (the mortality rate of hepatic carcinoma
      was 33.12/100 000(1068/3 224 562) ), the RR values of the hepatic carcinoma
      mortality was 1.38(95%CI:1.06-1.82) for the villages apart from the polluted
      river within 6 km (the mortality rate of hepatic carcinoma was 42.48/100
      000(777/1 829 064)), and 1.13 (95%CI:0.92-1.39) for villages apart from the river
      between 6 and 12 km (the mortality rate of hepatic carcinoma was 35.65/100
      000(651/1 825 848)). In the BYM model multivariate analysis, adding the volume of
      fertilizer and pesticides used per cultivated area, GDP per capita to do
      multivariate analysis were, the relation between mortality rate of hepatic
      carcinoma and distance from polluted rivers remains unchanged. CONCLUSION: The
      mortality rate of hepatic carcinoma was associated with the exposure to the
      polluted river in Lingbi county. The polluted river may increase the hepatic
      carcinoma mortality of nearby residents.

PMID- 24113103
TI  - [The human body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans and
      dioxin-like polychlorinated biphenyls in residents' human breast milk from
      Beijing in 2007].
AB  - OBJECTIVE: To investigate contamination levels of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl
      PCBs) in human breast milk from Beijing residents, and evaluate the human body
      burden of PCDD/Fs and dl-PCBs of general population. METHODS: A total of 110
      human milk samples were collected from 11 regions in Beijing in 2007. After 11
      pooled samples were made, concentrations of PCDD/Fs and dl-PCBs in breast milk
      pooled samples were measured by a high resolution gas chromatography - high
      resolution mass spectrometry (HRCG-HRMS) with isotope dilution. RESULTS: For
      congeners of PCDD/Fs and dl-PCBs in human breast milk from Beijing, the highest
      content of congeners was octachlorodibenzo-p-dioxin (OCDD), polychlorinated
      biphenyl (PCB)-118, and PCB-105 with the median of 20.6 pg/g fat, 4.07 ng/g fat
      and 1.63 ng/g fat, respectively. The concentration median of total dioxins in 11
      pooled human milk samples from Beijing was 7.4 pg TEQ/g fat. The highest was 13.5
      pg TEQ/g fat from Tongzhou, and the lowest was 4.3 pg TEQ/g fat from Pinggu.
      CONCLUSION: The contamination level of PCDD/Fs and dl-PCBs in human milk from
      Beijing is relatively low. However, with the rapid industrialization in China,
      the human body burden of PCDD/Fs and dl-PCBs will be likely to rise. Thus,
      further studies should be conducted to continuously monitor the trend of
      contamination level.

PMID- 24113104
TI  - [Association of polymorphisms of potassium voltage-gated channel, KQT-like
      subfamily, member 1 and type 2 diabetes in Jiangsu province, China].
AB  - OBJECTIVE: To study the association of polymorphisms in the potassium voltage
      gated channel, KQT-like subfamily,member 1(KCNQ1) gene with type 2 diabetes in
      Chinese population from Jiangsu province. METHODS: Subjects consisting of 2925
      cases and 3281 controls were enrolled from a community based cohort study of type
      2 diabetes in Wuxi in 2007 and a community based cross-sectional survey on
      chronic non-communicable disease in Nantong in 2009. Epidemiological
      questionnaire survey and physical examinations were conducted and 10 h overnight
      fasting blood samples of 5 ml were drawn for all subjects.Genotypes were
      determined by TaqMan OpenArray Genotyping System and i-PLEX Sequenom MassARRAY
      platform. The relationship between KCNQ1 gene polymorphism and risk of type 2
      diabetes after adjustment for age,sex and body mass index (BMI) was analyzed.
      RESULTS: The C allele of rs2237897, rs2237892 and rs2237895 at KCNQ1 increased
      the risk of type 2 diabetes with adjusted OR (95%CI) value being 1.41(1.30-1.54),
      1.35(1.24-1.47), 1.22(1.12-1.33) respectively (all P value < 0.05) under the
      additive genetic model after adjusted by age,sex and BMI. Stratification analyses
      in additive genetic model showed that the C allele of rs2237897 increased the
      risk of type 2 diabetes in subgroups stratified by age ( <= 56 years and > 56
      years), sex (females and males), BMI (< 24 kg/m(2) and >= 24 kg/m(2)) with OR
      (95%CI) value being 1.39(1.22-1.59), 1.43(1.28-1.60), 1.40(1.26-1.55), 1.44(1.26
      1.66), 1.48(1.33-1.66), 1.34(1.17-1.53) respectively (all P value< 0.05).
      CONCLUSION: Polymorphisms of rs2237897, rs2237892 and rs2237895 in the KCNQ1 gene
      were associated with occurrence of type 2 diabetes among Jiangsu province
      population.

PMID- 24113105
TI  - [Impact of evening exercise on college students' sleep quality].
AB  - OBJECTIVE: To investigate the impact of college students' evening exercise on
      their sleep quality, so as to provide a scientific basis for college students to
      choose an appropriate method of exercise and improve their sleep quality.
      METHODS: From September to October in 2012, Multi-stage cluster random sampling
      method was used to select the 5997 college students in Anhui province. The status
      of college students' exercise and their sleep quality were investigated by the
      general situation questionnaire, Physical activity rating scale-3(PARS-3), Rating
      of perceived exertion(RPE) and Pittsburgh sleep quality index(PSQI). Kruskal
      Wallis test was used to analyze the impact of evening exercise on sleep quality
      and multivariate unconditional logistic regression was used to analyze the
      factors of sleep quality in evening excise students. RESULTS: The median of PSQI
      total score among 5806 college students was 5 and 1030(17.7%) students had poor
      sleep quality. The median of the PSQI scores was the same (5 points) for evening
      exercise group, daytime exercise group,daytime and evening exercise group and non
      exercise group (1406, 1514, 1244, 1642 respectively). The difference was not
      statistically significant (chi(2) = 2.80, P = 0.42). Compared to non-exercise
      population, the OR (95%CI) value of evening exercise' impact on sleep quality was
      0.90(0.73-1.10). Compared to very light evening exercise, the OR (95%CI) value of
      moderate and large amount of evening exercise' impact on sleep quality was 0.58
      (0.44-0.75) and 0.67 (0.48-0.93) respectively; Compared to other sports, the OR
      (95%CI) value of badminton, rope skipping and jogging' impact on sleep quality
      was 0.72 (0.55-0.93), 0.38 (0.21-0.70) and 0.76 (0.60-0.95) respectively and they
      were all protective factors of sleep quality. Compared to small exercise
      intensity, the OR (95%CI) value of moderate, vigorous and very vigorous exercise
      intensity' impact on sleep quality was 1.68 (1.13-2.52), 2.38 (1.48-3.83) and
      3.18 (1.72-5.90) respectively and they were harmful factors of sleep quality.
      CONCLUSION: There was no impact of evening exercise on sleep quality for college
      students. Type of sports should be adequately chosen for evening exercise.
      College students can take moderate and large amount of evening exercise but
      should avoid activities of vigorous intensity.

PMID- 24113106
TI  - [Cost-effectiveness analysis of HIV testing strategy in hospitals from 2006 to
      2010 in Guangzhou].
AB  - OBJECTIVE: To evaluate the cost effectiveness of HIV testing strategy in
      hospitals from 2006 to 2010 in Guangzhou. METHODS: According to the HIV test
      strategy costs and the number of HIV patients found in Guangzhou, following
      aspects were calculated as the total cost of HIV testing strategy in hospitals
      from 2006 to 2010 of Guangzhou, the cost of finding each HIV patient, and the
      cost of obtaining one quality adjusted life year (QALY) using Markov model.
      RESULTS: The total HIV test strategy costs increased from 11 106.98 thousand Yuan
      to 25 105.58 thousand Yuan, and 4599 HIV positive patients were found due to this
      strategy. The cost-effectiveness of HIV testing were different in hospitals from
      2006 to 2010 in Guangzhou. The lowest cost-effectiveness ratio of HIV testing
      strategy was 11 810 Yuan per HIV positive patient, the highest was 23 510 Yuan,
      and the average was 16 070 Yuan. According to the Markov model result, 7.2855
      QALYs could be gained per HIV patient on average via HIV testing strategy in 113
      hospitals in Guangzhou, and the cost of obtaining one QALY was 2210 Yuan.
      CONCLUSION: The cost effectiveness ratio of HIV testing strategy in hospitals in
      Guangzhou was significantly lower than the standard of WHO recommended, and it
      was cost-effective to carry out the HIV testing strategy in Guangzhou.

PMID- 24113107
TI  - [Fatty acid composition of edible marine fish in Zhoushan, Zhejiang province].
AB  - OBJECTIVE: To analyze the main fatty acids in edible marine fish from Zhoushan,
      Zhejiang province. METHODS: From September to October 2011, a total of 186 edible
      marine fish (31 species,6 individual fishes/species) were collected in local
      markets. Total lipids of edible part were extracted by Folch's method and fatty
      acids were separated and quantified by gas chromatographic after the
      homogenization of edible part. The differences of composition of n-6
      polyunsaturated fatty acid (n-6 PUFA), n-3 polyunsaturated fatty acid (n-3
      PUFA),saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) among
      fishes were analyzed. RESULTS: Among the 31 fishes, total lipids were highest in
      Auxis thazard ((13.2 +/- 1.2)g/100 g edible part) and lowest in Thamnaconus
      modestus ((0.6 +/- 0.1)g/100 g edible part). Total n-6 PUFA were highest in Mugil
      cephalus ((875.7 +/- 506.4)mg/100 g edible part) and lowest in Seriola
      quinqueradiata((2.1 +/- 1.9)mg/100 g edible part). Total n-3 PUFA were highest in
      Auxis thazard ((2623.8 +/- 426.1)mg/100 g edible part) and lowest in Scoliodon
      sorrakowah ((82.0 +/- 13.9)mg/100 g edible part). SFA were highest in Trachinotus
      ovatus((3014.9 +/- 379.0)mg/100 g edible part) and lowest in Seriola
      quinqueradiata ((89.7 +/- 5.8)mg/100 g edible part). MUFA were highest in Coilia
      nasus ((3335.7 +/- 383.5)mg/100 g edible part) and lowest in Thamnaconus modestus
      ((32.1 +/- 16.9)mg/100 g edible part). CONCLUSION: There were significant
      differences of composition of total lipids and of fatty acids among 31 edible
      marine fish species from Zhoushan.

PMID- 24113108
TI  - [The influence of microcystin-LR on monocytes and lymphocytes of mice].
AB  - OBJECTIVE: To investigate the influence of microcystin-LR (MC-LR) on monocytes
      and lymphocytes in blood of mice and to find a sensitive index of toxic effects.
      METHODS: Specific pathogen free Kunming male mice, aging 1 month-old,were
      randomly divided into 5 groups by weights, 7 mice for each group. The mice in 5
      groups were exposed to MC-LR through intraperitoneal injection at 0, 3.125,6.250,
      12.500 and 25.000 ug/kg respectively for 7 days. Then cytokine levels in the
      serum were measured by radioimmunoassay, DNA-protein crosslinks (DPC) was
      measured by the SDS/KCl precipitation technique, and the phagocytosis and ROS of
      leukocytes were detected by flow cytometry. RESULTS: The levels of interleukin 6
      in the 6.250, 12.500 and 25.000 ug.kg(-1).d(-1) dose groups were (346.837 +/-
      25.536), (360.847 +/- 37.886) and (434.245 +/- 35.858)pg/ml respectively, which
      were significantly higher than those in the control group which the value was
      (232.775 +/- 32.816) pg/ml (t values were -7.258, -6.760 and -10.966
      respectively, P values were all < 0.05).While the level of tumor necrosis factor
      alpha was(10.782 +/- 0.966) fmol/ml in 25 ug.kg(-1).d(-1) dose group was
      statistically lower than it in the control group which the value was (16.878 +/-
      3.378) fmol/ml (t value was 4.591, P < 0.05). The DPC levels of lymphocytes in
      6.250, 12.500 ug.kg(-1).d(-1) dose group were (242.576 +/- 7.545),(241.472 +/-
      2.793) ng/ml,higher than it in the control group while the value was (228.657 +/-
      4.130) ng/ml (t value was -4.282, -6.801, P values were all <0.05). The
      fluorescence intensity of DCF in lymphocytes in the 4 treated groups were
      separately 3299.37 +/- 120.54, 3281.38 +/- 58.34, 3308.06 +/- 136.12 and 3346.92
      +/- 108.69, all significantly lower than 3770.81 +/- 131.39 in the control group
      (t values were 6.995, 9.007, 6.472 and 6.577 respectively, and P values were all
      <0.05). The fluorescence intensity of DCF in monocytes in the 4 treated groups
      (3271.51 +/- 140.79, 3270.05 +/- 117.92, 3326.90 +/- 114.39 and 3292.49 +/-
      145.97 respectively) were also significantly lower than the value in the control
      group was 3841.72 +/- 130.92 (t values were 7.847, 8.584, 7.835 and 7.411
      respectively, P values were all <0.05). There was no significant difference in
      other index among the four experiment groups and the control group. CONCLUSION:
      The MC-LR administered via intraperitoneal injection to mice induced the
      alterations of some cytokines of monocytes and lymphocytes in blood. By
      comparison, the ROS of leukocyte was the most sensitive index.

PMID- 24113109
TI  - [Influence of chronic fluorosis on the expression of mitochondrial fission
      protein dynamin-related 1 in the cortical neurons of rats].
AB  - OBJECTIVE: To explore the changes of protein expression of mitochondrial fission
      gene dynamin-related 1(Drp 1) in the cortical neurons of rats with chronic
      fluorosis. METHODS: A total of 120 one-month-old SD rats (each weighing
      approximately 100-120 g at the beginning of the experiment) were randomly divided
      into three groups, and fed with the different doses of fluoride containing in
      drinking water (untreated control containing 0 mg/L fluoride, and low-fluoride &
      high-fluoride supplemented with 10 and 50 mg/L fluoride,respectively). After 3 or
      6 months exposure, 20 rats from each group were killed. Then the protein
      expression of mitochondrial fission gene, Drp1, was detected by
      immunohistochemistry and western-blotting method. RESULTS: Dental fluorosis and
      urinary fluorosis were obviously found in the rats exposed to fluoride. At the
      experiment period of 3 months, the numbers of positive cells of Drp1 detected by
      immunohistochemistry changed. Compared with the control group (36.3 +/- 5.8), the
      changes in low-fluoride group (34.7 +/- 4.1) showed no significant difference (t
      = 1.5, P > 0.05),but the increase in high-fluoride group (45.0 +/- 4.7) had
      statistical significance (t = 8.8, P < 0.05). The western-blotting method had
      consistent results. Compared with the control group (0.59 +/- 0.03), a
      significant increase of the average topical density in low- fluoride (0.62 +/-
      0.03) and high-fluoride (0.71 +/- 0.02) groups were found (t = 0.02,0.11, P <
      0.05). At the experiment period of 6 months, the numbers of positive cells of
      Drp1 detected by immunohistochemistry significantly changed. Compared with the
      control group (33.2 +/- 4.4), the number in low- fluoride and high-fluoride
      groups were separately (36.6 +/- 3.8) and (39.4 +/- 4.2),both increased
      significantly (t = 3.5,6.3, P < 0.05). Same results could be found in western
      blotting method,compared with the control group (0.65 +/- 0.06), the average
      topical density in low- fluoride (0.80 +/- 0.09) and high-fluoride (0.76 +/-
      0.08) groups both increased significantly (t = 0.1,0.1, P < 0.05). CONCLUSIONS:
      Taking excessive amount of fluoride might result in the changes of expression of
      Drp1, and the neurons damage from the chronic fluorosis might be associated with
      the hyperfunction of mitochondrial fusion.

PMID- 24113110
TI  - [Development of a model diets for consumers with high exposure to food
      chemicals].
AB  - OBJECTIVE: To develop and verify a model diet for consumers with high exposure to
      food chemicals. METHODS: Based on the assumption that a person might consume
      average amounts of several different foods but only two or three at high levels,
      a model diet were put forward to calculate the high exposures to certain food
      chemical.Important parameters of this model were selected by comparing the
      outputs of this model with those of a reference model-semi-probabilistic model
      that is based on individual data. The concentration data of lead, cadmium and
      mercury (45 832, 43 862 and 25 243 samples respectively) from the national risk
      surveillance for chemical contaminations and harmful factors (2011), and the
      consumption data from the national survey on nutrition and health status in
      Chinese population (2002) were used in this model optimization process. The final
      model was verified using concentration data of eight chemical contaminations from
      national surveillance database of 2010. RESULTS: When 90, 95 and 97.5 percentile
      exposure being calculated under the conditions that 7, 12, 20 and 30 food
      categories was used respectively, the model containing two high consumption foods
      (2+x model) got results lower than the reference values (the relative deviation <
      0) , the model containing three high consumption foods (3+x model) got results
      higher than the reference values (the relative deviation > 0 ),but the relative
      deviation of the two models were both within 20%. The verification results showed
      that the dietary exposure results of 8 food contaminations got from 3+x model
      were all higher than and(or) close to those got from semi-probabilistic model,
      and the relative deviations were between -5% and 25%. CONCLUSION: The 3+x model
      diet can fulfill the demands of "conservative" and "accurate" on exposure
      assessment model, and can give reliable estimations of high exposure to food
      chemicals occurred in various food categories.

PMID- 24113111
TI  - [Applicability of thresholds of toxicological concern in the chronic dietary risk
      assessment of transformation products of pesticide active substance].
AB  - OBJECTIVE: To establish the threshold of toxicological concern(TTC) approach and
      to apply it in the risk assessment of metabolites, degradation and reaction
      products of pirimicarb. METHODS: TTC decision tree approach based on Cramer
      classification was established and Lazar software was used to predict the
      genotoxicity of the seven transformation products of pirimicarb, namely, R34836,
      R34885, R35140, R31805, R34865, R16210 and R16192. Dietary exposure in general
      population as well as in six age population groups was estimated by using data
      from the Chinese National Nutrition and Health Survey and pirimicarb residue data
      from national chemical surveillance data in 2011. TTC decision tree approach was
      used for risk assessment and the exposure was compared with the corresponding TTC
      values. RESULTS: Of the seven transformations of pirimicarb active substance,
      namely, R34836, R34885, R35140, R31805, R34865, R16210 and R16192, the maximum
      dietary exposure of mean and large portion(P 97.5) were all belong to 2-6 age
      group. The mean exposures of the seven transformation products for 2-6 age
      group,were 0.0290, 0.0207, 0.0015, 0.0320, 0.0005, 0.6918 and 0.1274
      ug/kg,respectively, and the corresponding P 97.5 exposures were
      0.0817,0.0581,0.0042,0.0900,0.0014, 1.9459 and 0.3585 ug/kg. Besides, the mean
      and P 97.5 exposure of R16210 for 2-6 age group was the largest,which were 0.6918
      and 1.9459 ug/kg, accounting for 46.12% and 129.73% of the TTC
      threshold,respectively. CONCLUSION: TTC decision tree approach is a useful tool
      for prior screening and primary risk assessment of the transformation products of
      pesticide active substance.

PMID- 24113112
TI  - Activation of urocortin 1 and ghrelin signaling in the basolateral amygdala
      induces anxiogenesis.
AB  - Prior anatomical and functional studies have demonstrated the importance of the
      basolateral region of the amygdala in the regulation of anxiogenic and anxiolytic
      behaviors. In the present report we investigated the anxiety-inducing effects of
      the corticotropin-releasing hormone-related peptide urocortin 1 (Ucn1) and the
      gut-brain peptide ghrelin. Both peptides were injected directly into the
      basolateral amygdala of male Sprague-Dawley rats and performance in the elevated
      plus maze was assessed. Ghrelin was administered at doses of 3-300 pmol and Ucn1
      at doses of 0.01-1.0 pmol. Separate groups of rats were pretreated with Ucn1
      before ghrelin treatment. In all experiments each test was performed as a single
      trial per animal. Results indicated that both ghrelin and Ucn1 elicited an
      increase in anxiogenic behavior. Moreover, Ucn1 pretreament potentiated the
      anxiogenic action of ghrelin. Overall these findings provide support for an
      integrated role of ghrelin and urocortin signaling within the basolateral
      amygdala in the expression of anxiogenesis. 

PMID- 24113113
TI  - Cerebellar-related long latency motor response in upper limb musculature by
      transcranial magnetic stimulation of the cerebellum.
AB  - In this study, we aimed to identify the cerebellum-related electromyographic
      (EMG) response that appeared in the upper limbs musculature. Thirty times
      averaged transcranial magnetic stimulation (TMS) with a double-cone coil placed
      over the cerebellar hemisphere elicited long latency EMG responses at the
      bilateral extensor carpi radialis (ECR) muscles. The peak latency of this EMG
      response was 70.7+/-12.7 ms in the ipsilateral ECR and 62.9+/-10.2 ms in the
      contralateral ECR of the TMS side. These latencies were much longer than the
      latency of the muscle evoked potential when we stimulated pyramidal tracts at the
      foramen magnum level. Cerebellar hemisphere loading by the finger target pursuit
      test made this EMG response faster during TMS on the ipsilateral side of the
      cerebellum and slower during TMS on the contralateral side of the cerebellum.
      Furthermore, the deeper the level of drowsiness, the slower the peak latency of
      this EMG response became. These results suggest that this EMG potential is a
      specific response of the cerebellum and brainstem reticular formation, and may be
      conducted from the cerebellar structure to the ECR muscle through the
      polysynaptic transmission of the reticulospinal tract. 

PMID- 24113114
TI  - Stimulus frequency otoacoustic emissions evoked by swept tones.
AB  - Otoacoustic emissions (OAEs) are soft sounds generated by the cochlea and the
      measurements of OAEs are useful in detecting cochlear damages. Stimulus frequency
      otoacoustic emissions (SFOAEs) are evoked by one single tone and they are the
      most frequency specific in probing functional status of the cochlea than other
      types of OAEs. However, SFOAEs are currently restricted to research only because
      of the difficulty and low efficiency of their measurements. To solve these
      problems, an efficient method of using swept tones to measure SFOAEs was proposed
      in this study. The swept tones had time-varying frequencies and therefore could
      efficiently measure SFOAEs over a wide frequency range with a resolution
      dependent on the sweep rate. A three-interval paradigm and a tracking filter were
      used to separate the swept-tone SFOAEs from background noises. The reliability of
      the swept-tone SFOAEs was examined by a repeated-measure design, and the accuracy
      was evaluated by the comparison with a standard method using pure tones as the
      stimuli. The pilot results of this study showed that SFOAEs could be measured
      successfully using swept tones in human ears with normal hearing. The amplitude
      and phase of the swept-tone SFOAEs were highly reproducible in the repeated
      measures, and were nearly equivalent to SFOAEs evoked by pure tones under various
      signal conditions. These findings suggest that the proposed swept-tone SFOAEs
      could be a useful method in estimating the cochlear functions and developing an
      efficient approach of OAE measurements to help with accurate hearing diagnoses in
      the clinic. 

PMID- 24113115
TI  - Neuronal basis of speech comprehension.
AB  - Verbal communication does not rely only on the simple perception of auditory
      signals. It is rather a parallel and integrative processing of linguistic and non
      linguistic information, involving temporal and frontal areas in particular. This
      review describes the inherent complexity of auditory speech comprehension from a
      functional-neuroanatomical perspective. The review is divided into two parts. In
      the first part, structural and functional asymmetry of language relevant
      structures will be discus. The second part of the review will discuss recent
      neuroimaging studies, which coherently demonstrate that speech comprehension
      processes rely on a hierarchical network involving the temporal, parietal, and
      frontal lobes. Further, the results support the dual-stream model for speech
      comprehension, with a dorsal stream for auditory-motor integration, and a ventral
      stream for extracting meaning but also the processing of sentences and
      narratives. Specific patterns of functional asymmetry between the left and right
      hemisphere can also be demonstrated. The review article concludes with a
      discussion on interactions between the dorsal and ventral streams, particularly
      the involvement of motor related areas in speech perception processes, and
      outlines some remaining unresolved issues. This article is part of a Special
      Issue entitled Human Auditory Neuroimaging.

PMID- 24113116
TI  - Effects of symbiotic food consumption in diabetic patients: reply to Wachholz PA
      et al.

PMID- 24113117
TI  - [Vesical esquistosomiasis: a new imported case].

PMID- 24113118
TI  - [Ante-natal corticosteroids and prevention of respiratory distress in the
      premature newborn: usefulness of rescue treatment].
AB  - The effectiveness of antenatal corticosteroid therapy for foetal lung maturation
      in pre-term infants is well known, but there is uncertainty about the time that
      the treatment remains effective. A descriptive, longitudinal study was conducted
      to determine whether the need for surfactant administration was determined by the
      time-lapse between corticosteroids administration and delivery, and when
      repeating the doses of maternal corticosteroids should be considered. A total of
      91 premature infants <=32 weeks and/or <=1,500 g (limit 34+6 weeks) whose mothers
      had received a complete course of corticosteroids were included. In patients at
      27-34+6 weeks, we found that the longer the time elapsed between delivery and
      administration of corticosteroids, most likely were the babies to require
      treatment with surfactant (P=.027). The resulting ROC curve determined an 8-days
      cut-off after which repeating a dose of corticosteroids should be assessed. 

PMID- 24113119
TI  - [Hypothermia risk factors in the very low weight newborn and associated morbidity
      and mortality in a neonatal care unit].
AB  - INTRODUCTION: Heat loss in the newborn after delivery could interfere with post
      natal adaptation due to metabolic and hemodynamic instability. Associated
      perinatal factors and their relationship with morbidity and mortality during the
      neonatal period have not been systematically studied in our unit. OBJECTIVES: To
      determine the temperature of very low birth weight (VLBW) infants on admission to
      our NICU, and to determine the associated perinatal variables, and the
      association of temperature with morbidity and mortality. PATIENTS AND METHODS:
      Infants born in our maternity from January 2006 to November 2012, with birth
      weights (BW) 401 g to 1,499 g and/or less than 30 weeks gestational age, were
      included. A multivariate analysis was performed using the perinatal variables and
      the temperature on admission, as well as a logistic regression between these and
      the morbidity-mortality variables, in order to detect any independent
      associations. RESULTS: A total of 635 infants were included, with a mean (+/- SD)
      birth weight and gestational age of 1,137.6 +/- 257.6g, and 29.5 +/- 2.0 weeks,
      respectively. The mean admission temperature was 35.8 +/- 0.6 degrees C (range:
      33.0-37.8 degrees C). The proportion of infants with a temperature < 36 degrees C
      was 44.4%. Independently associated perinatal variables were chorioamnionitis,
      birth weight, vaginal delivery, and advanced cardiopulmonary resuscitation (CPR).
      Admission hypothermia was associated with severe intraventricular haemorrhage
      (IVH) (grades 3 and 4) (OR: 0.377; 95% CI: 0.221-0.643; P<.001), and mortality
      (OR: 0.329; 95% CI: 0.208-0.519; P=.012). CONCLUSIONS: Hypothermia on admission
      is frequent among our VLBW infants. Birth weight, vaginal delivery, and advanced
      CPR were the principal variables associated with hypothermia. A low temperature
      on admission was related to an increased risk of IVH and mortality.

PMID- 24113120
TI  - [New population curves in spanish extremely preterm neonates].
AB  - INTRODUCTION: Most anthropometric reference data for extremely preterm infants
      used in Spain are outdated and based on non-Spanish populations, or are derived
      from small hospital-based samples that failed to include neonates of borderline
      viability. OBJECTIVES: To develop gender-specific, population-based curves for
      birth weight, length, and head circumference in extremely preterm Caucasian
      infants, using a large contemporary sample size of Spanish singletons. PATIENTS
      AND METHODS: Anthropometric data from neonates <= 28 weeks of gestational age
      were collected between January 2002 and December 2010 using the Spanish database
      SEN1500. Gestational age was estimated according to obstetric data (early
      pregnancy ultrasound). The data were analyzed with the SPSS.20 package, and
      centile tables were created for males and females using the Cole and Green LMS
      method. RESULTS: This study presents the first population-based growth curves for
      extremely preterm infants, including those of borderline viability, in Spain. A
      sexual dimorphism is evident for all of the studied parameters, starting at early
      gestation. CONCLUSIONS: These new gender-specific and population-based data could
      be useful for the improvement of growth assessments of extremely preterm infants
      in our country, for the development of epidemiological studies, for the
      evaluation of temporal trends, and for clinical or public health interventions
      seeking to optimize fetal growth.

PMID- 24113122
TI  - Relationship between insulin resistance, dyslipidaemia and positive symptom in
      Chinese antipsychotic-naive first-episode patients with schizophrenia.
AB  - Controversial results concerning insulin resistance and lipid metabolism have
      been reported in antipsychotic-naive first-episode psychosis (AN-FEP) patients
      with schizophrenia of different countries. We aimed at determining whether
      schizophrenia-related psychopathology was associated with insulin resistance
      and/or dyslipidaemia in Chinese patients with AN-FEP schizophrenia. A cross
      sectional study was performed in Chinese patients newly diagnosed with
      schizophrenia (n = 49, antipsychotic-naive or antipsychotic medications< 2 weeks)
      and healthy volunteers (n = 30). The serum levels of insulin and triglyceride
      levels as well as homeostasis model of assessment-insulin resistance (HOMA-IR)
      index were significantly increased in AN-FEP patients, when compared with healthy
      volunteers. The gender difference had a significant impact on the insulin
      resistance and dyslipidaemia in these AN-FEP subjects. Multiple linear regression
      analysis demonstrated that the severity of positive symptoms of schizophrenia was
      negatively related to insulin resistance. No difference of serum glucose level,
      total cholesterol content, body mass index (BMI) and smoking status was detected
      between patients with schizophrenia and healthy controls. In conclusion, Chinese
      AN-FEP patients were more prone to insulin resistance and dyslipidaemia as
      compared to the healthy population, which is negatively correlated to positive
      symptoms. The results may contribute to the understanding of the relationship
      between the glucose/lipidaemia metabolic dysfunction and the psychopathology in
      patients with schizophrenia. 

PMID- 24113121
TI  - A genome-wide analysis of annexins from parasitic organisms and their vectors.
AB  - In this study, we conduct an in-depth analysis of annexin proteins from a diverse
      range of invertebrate taxa, including the major groups that contain the parasites
      and vector organisms that are harmful to humans and domestic animals. Using
      structure-based amino acid sequence alignments and phylogenetic analyses, we
      present a classification for this protein group and assign names to sequences
      with ambiguous annotations in public databases. Our analyses reveal six distinct
      annexin clades, and the mapping of genes encoding annexins to the genome of the
      human blood fluke Schistosoma mansoni supports the hypothesis of gene duplication
      as a major evolutionary event in annexin genesis. This study illuminates annexin
      diversity from a novel perspective using contemporary phylogenetic hypotheses of
      eukaryote evolution, and will aid the consolidation of annexin protein identities
      in public databases and provide a foundation for future functional analysis and
      characterisation of these proteins in parasites of socioeconomic importance. 

PMID- 24113123
TI  - Evaluation of physical fitness parameters in patients with schizophrenia.
AB  - The aims of this study were to compare aerobic and anaerobic exercise capacities,
      pulmonary functions, body composition and fat distribution parameters in patients
      with schizophrenia and healthy controls and to investigate the associations among
      these parameters. Sixty (30 male, 30 female) patients with schizophrenia and 60
      (30 male, 30 female) healthy controls were included in the study. Maximal aerobic
      capacity was estimated with the Astrand submaximal exercise protocol, and
      anaerobic performance was determined with a Wingate test. Body composition was
      established with a bioelectrical impedance analyzer. Pulmonary function tests,
      skinfold thickness and body circumference measurements were also carried out.
      Maximal aerobic capacity, maximal anaerobic power, anaerobic capacity and
      pulmonary function tests (forced vital capacity and maximal voluntary
      ventilation) were found to be lower in male and female schizophrenic groups as
      compared to the controls. Body fat percentage, waist and abdomen circumferences,
      and waist to hip ratio were found to be higher in female schizophrenic patients
      than in controls. We suggest that maximal aerobic capacity, maximal anaerobic
      power, and anaerobic capacity are poor in the schizophrenia patients as compared
      to healthy controls. Low cardiorespiratory fitness is related to reduced
      pulmonary function and impaired body composition in schizophrenia patients. 

PMID- 24113124
TI  - Social support and functional outcome in severe mental illness: the mediating
      role of proactive coping.
AB  - Individuals with Severe Mental Illness (SMI) are faced with wide-spread social
      and occupational impairment, yet some are able to achieve a meaningful degree of
      functional improvement. A structural model based on Proactive Coping Theory was
      developed and tested in a longitudinal context to better understand: (1) the
      impact of proactive processes on functioning for people with SMI, and (2) the
      stability of the theoretical framework over time for this population. A latent
      path analysis examining social support, positive reappraisal, intrinsic
      motivation, and role functioning was tested with 148 severely mentally ill
      individuals receiving psychosocial rehabilitation treatment at baseline. An
      observed path analysis of the model was examined at six months post-baseline with
      102 people. The baseline model displayed an excellent fit to the data and
      accounted for 54% of the variance in role functioning. Results at time 2 also
      suggest the empirical promise and potential longitudinal viability of the model.
      In line with Proactive Coping Theory and a social resources model of coping,
      social support may facilitate proactive coping processes to enhance role
      functioning, and these processes may be stable over time for people with SMI. 

PMID- 24113125
TI  - Left versus right repetitive transcranial magnetic stimulation in treating major
      depression: a meta-analysis of randomised controlled trials.
AB  - Although the majority of randomised controlled trials suggest that major
      depressive disorder (MDD, major depression) and treatment-resistant depression
      can be effectively treated by applying either high- (HF) or low-frequency (LF)
      repetitive transcranial magnetic stimulation (rTMS) to the left and right
      dorsolateral prefrontal cortex (DLPFC), respectively, it is not clear which rTMS
      approach is more effective or safer. This systematic review and meta-analysis was
      conducted on randomised controlled trials on HF and LF rTMS applied to the left
      and right DLPFC, respectively, for the treatment of MDD. Eight randomised
      controlled trials composed of 249 patients were selected to compare the effects
      of LF (<= 1 Hz) rTMS over the right DLPFC to HF (10-20 Hz) rTMS over the left
      DLPFC. The therapeutic effects of both approaches were similar (odds ratio (OR) =
      1.15; 95% confidence interval = 0.65-2.03). Dropout analysis based on only two
      studies was insufficient to draw a conclusion on the tolerability of LF rTMS. The
      pooled examination demonstrated that both rTMS methods were equally effective
      therapies for MDD. However, considering that LF right-sided rTMS produces fewer
      side effects and is more protective against seizures, its clinical applicability
      shows greater promise and should be explored further.

PMID- 24113126
TI  - Neurotransmitter receptor and regulatory gene expression in peripheral blood of
      Brazilian drug-naive first-episode psychosis patients before and after
      antipsychotic treatment.
AB  - Little is known about how genes expressed in blood relate to schizophrenia or
      antipsychotic use. We analyzed gene expression in 10 first-episode psychosis
      patients and nine controls using PCR Arrays. GABRR2 and CHRNA3 were found to be
      differentially expressed after risperidone treatment. These genes may be
      regulated by antipsychotic use. 

PMID- 24113127
TI  - Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated
      patients with schizophrenia.
AB  - Oxidative stress has been implicated in the pathophysiology of schizophrenia.
      Taurine and glutathione (GSH) have antioxidant and central nervous system
      protective properties, and are proposed to be involved in the pathology of
      schizophrenia. The aim of this study was to compare the blood and cerebrospinal
      fluid (CSF) levels of taurine and GSH in patients with schizophrenia, medicated
      with oral olanzapine, compared with controls. In total, 37 patients with
      schizophrenia and 45 healthy volunteers were recruited. We found the plasma
      taurine levels to be elevated in patients compared with controls. No differences
      were, however, found between patients and controls regarding taurine in CSF or
      GSH concentrations in plasma and CSF. Moreover, in the patient group no
      correlations between taurine and GSH levels and the symptoms or function of the
      disorder were found. The higher levels of plasma but not CSF taurine in patients
      with schizophrenia treated with OLA may implicate the involvement of taurine in
      the pathophysiology of the disease. The absence of GSH differences both in plasma
      and CSF between patients and controls is interesting in the perspective of
      earlier research proposing a dysregulation of GSH metabolism as a vulnerability
      factor for the development of schizophrenia. 

PMID- 24113129
TI  - Impact of oral fluids on dental ceramics: what is the clinical relevance?
AB  - OBJECTIVES: In this brief and selective overview, basic factors contributing to
      aqueous induced dissolution, phase changes of zirconia and mechanical strength
      degradation of dental ceramics are considered. METHODS: Dissolution is important
      for porcelain and glass-ceramic materials as they predominantly contain a silica
      glass structure with various other cations incorporated which disrupt the silica
      network. In glass-ceramic materials and porcelains containing crystalline
      components the situation is more complex as the difference in the dissolution
      rate may increase the surface roughness and contribute to abrasion of the
      opposing definition. RESULTS: Factors contributing to the aqueous dissolution of
      silicate based dental ceramics and induced destabilization of Y-TZP zirconia or
      low temperature degradation (LTD) are considered. It is also noted that there
      have been a number of reports of spontaneous fracture of 3Y-TZP specimens because
      of LTD in the absence of external stress. A simple analysis of this situation is
      presented which indicates a strong specimen-size effect and also implicates the
      role of the remnant "pseudo-grain" structure resulting from the pressing of spray
      dried powder agglomerates. SIGNIFICANCE: The final section of this review
      addresses the consequences of various environments on crack growth and strength
      degradation. In some situations it is suggested that the aqueous environment may
      enhance the strength of restorative materials. In all instances discussed above
      the clinical consequences are pointed out.

PMID- 24113128
TI  - Notch3 inhibition enhances sorafenib cytotoxic efficacy by promoting GSK3b
      phosphorylation and p21 down-regulation in hepatocellular carcinoma.
AB  - Sorafenib (Nexavar), a multiple kinase inhibitor, is the only clinically approved
      drug for patients with advanced HCC. However, its therapeutic success is limited
      by the emergence of drug resistance. Here we found that p21 and pGSK3betaSer9 are
      major players in the resistance to sorafenib. We recently reported that aberrant
      Notch3 expression in HCC contributes to doxorubicin resistance in vitro and,
      therefore, we focused on the mechanisms that associate Notch3 to acquired drug
      resistance. In this study we first found that Notch3 inhibition significantly
      increased the apoptosis inducing effect of sorafenib in HCC cells via specific
      down-regulation of p21 and up-regulation of pGSK3betaSer9. Using a mouse
      xenograft model we further found that Notch3 depletion combined with 21 days of
      sorafenib treatment exerts a substantial antitumor effect in vivo. Interestingly,
      we showed that, upon exposure to sorafenib treatment, Notch3 depleted xenografts
      maintain lower levels of p21 and higher levels of pGSK3betaSer9 than control
      xenografts. Thus, this study demonstrated that inhibition of Notch3 signaling
      prevents HCC-mediate drug resistance and sensitizes HCC cells to sorafenib.
      Finally, we validated our in vitro and in vivo results in primary human HCCs
      showing that Notch3 protein expression positively correlated with p21 protein
      expression and negatively correlated with pGSK3betaSer9 expression. In
      conclusion, the results presented in this study demonstrated that Notch3
      silencing enhances the effect of sorafenib by overcoming drug resistance. Notch3
      inhibition in combination with sorafenib can be a promising strategy for
      treatment of HCC. 

PMID- 24113130
TI  - From bench-top to chair-side: how scientific evidence is incorporated into
      clinical practice.
AB  - OBJECTIVES: The objective of this manuscript is to describe the process through
      which bench-top research is incorporated into clinical practice from an evidence
      based dentistry perspective. METHODS: Relevant literature is reviewed to describe
      the translation of bench-top research to clinical practice through the steps of
      preclinical testing; human clinical trials; systematic review development
      (question development, search/screen methods, evidence synthesis, and evidence
      appraisal); clinical recommendation development; dissemination strategies; the
      role of the clinician in finding and appraising relevant evidence; barriers to
      implementation with strategies to overcome those barriers; and finally, the
      fusion of evidence with clinician experience and patient needs and preferences in
      clinical decision-making. SIGNIFICANCE: Descriptions of processes, methodologies,
      tools, and resources are provided to help researchers and clinicians alike
      understand the steps that lie between bench-top research and clinical
      implementation. With mutual understanding of the complexity involved in
      translating research into practice, it is hoped that barriers to implementation
      can be overcome that should lead to improved patient health outcomes.

PMID- 24113131
TI  - Present and future of glass-ionomers and calcium-silicate cements as bioactive
      materials in dentistry: biophotonics-based interfacial analyses in health and
      disease.
AB  - OBJECTIVE: Since their introduction, calcium silicate cements have primarily
      found use as endodontic sealers, due to long setting times. While similar in
      chemistry, recent variations such as constituent proportions, purities and
      manufacturing processes mandate a critical understanding of service behavior
      differences of the new coronal restorative material variants. Of particular
      relevance to minimally invasive philosophies is the potential for ion supply,
      from initial hydration to mature set in dental cements. They may be capable of
      supporting repair and remineralization of dentin left after decay and cavity
      preparation, following the concepts of ion exchange from glass ionomers. METHODS:
      This paper reviews the underlying chemistry and interactions of glass ionomer and
      calcium silicate cements, with dental tissues, concentrating on dentin
      restoration interface reactions. We additionally demonstrate a new optical
      technique, based around high resolution deep tissue, two-photon fluorescence and
      lifetime imaging, which allows monitoring of undisturbed cement-dentin interface
      samples behavior over time. RESULTS: The local bioactivity of the calcium
      silicate based materials has been shown to produce mineralization within the
      subjacent dentin substrate, extending deep within the tissues. This suggests that
      the local ion-rich alkaline environment may be more favorable to mineral repair
      and re-construction, compared with the acidic environs of comparable glass
      ionomer based materials. SIGNIFICANCE: The advantages of this potential re
      mineralization phenomenon for minimally invasive management of carious dentin are
      self-evident. There is a clear need to improve the bioactivity of restorative
      dental materials and these calcium silicate cement systems offer exciting
      possibilities in realizing this goal.

PMID- 24113132
TI  - Biodegradation of resin composites and adhesives by oral bacteria and saliva: a
      rationale for new material designs that consider the clinical environment and
      treatment challenges.
AB  - OBJECTIVE: To survey the recent literature from the late 1980s to recent years in
      order to assess the relationship between resin degradation, catalyzed by
      biological factors, and clinical failure outcomes such as marginal breakdown.
      METHODS: The literature shows that degradation occurs in many manufacturers'
      products despite varied vinyl acrylate compositions. The authors examine salivary
      enzyme activity and their ability to degrade the polymeric matrix of resin
      composites and adhesives, as well as oral microorganisms that can promote
      demineralization of the tooth surface at the marginal interface. A survey of
      recent research relating matrix metalloproteinase (MMPs) to the degradation of
      the exposed collagen at the dentin adhesive interface is also discussed in the
      context of marginal breakdown. RESULTS: The literature provides strong support
      that together, the above factors can breakdown the marginal interface and limit
      the longevity of resin composite restorations. The authors have found that the
      field's current understanding of resin biodegradation in the oral cavity is just
      beginning to grasp the role of bacteria and enzymes in the failure of resin-based
      restorations. SIGNIFICANCE: Knowledge of these biodegradation processes is
      pertinent to areas where innovative strategies in the chemistry of restorative
      materials are anticipated to enhance the longevity of resin composites.

PMID- 24113133
TI  - S-nitroso albumin enhances bone formation in a rabbit calvaria model.
AB  - Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore
      examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO
      HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves
      (8 mm diameter, two per animal) were created by a trephine drill in the cortical
      bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone
      filled with a collagen sponge soaked with either 100 MUL S-NO-HSA (5%, 20%) or
      human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to
      histological and histomorphometric analysis. Bone formation and the volume of the
      residual collagen sponge were evaluated. S-NO-HSA treatment groups had a
      significantly higher volume of newly formed bone underneath the titanium
      hemispheres compared to the albumin control groups (5%: 15.5 +/- 4.0% versus 10.6
      +/- 2.9%; P < 0.05; 20%: 14.0 +/- 4.6% versus 6.0 +/- 3.8%; P < 0.01). The volume
      of residual collagen sponge was also significantly lower in the S-NO-HSA groups
      compared to the control groups (5%: 0.4 +/- 0.5% versus 2.6 +/- 2.4%; P < 0.05
      and 20%: 1.5 +/- 2.7% versus 13.0 +/- 18.7%; P < 0.01). This study demonstrates
      for the first time that S-NO-HSA promotes bone formation by slow NO release.
      Additionally, S-NO-HSA increases collagen sponge degradation.

PMID- 24113134
TI  - Re: "Treatment of low subcondylar fractures--a 5-year retrospective study".

PMID- 24113135
TI  - Development of 3D carbon nanotube interdigitated finger electrodes on polymer
      substrate for flexible capacitive sensor application.
AB  - This study reports a novel approach to the implementation of 3D carbon nanotube
      (CNT) interdigitated finger electrodes on flexible polymer, and the detection of
      strain, bending curvature, tactile force and proximity distance are demonstrated.
      The merits of the presented CNT-based flexible sensor are as follows: (1) the
      silicon substrate is patterned to enable the formation of 3D vertically aligned
      CNTs on the substrate surface; (2) polymer molding on the silicon substrate with
      3D CNTs is further employed to transfer the 3D CNTs to the flexible polymer
      substrate; (3) the CNT-polymer composite (~70 MUm in height) is employed to form
      interdigitated finger electrodes to increase the sensing area and initial
      capacitance; (4) other structures such as electrical routings, resistors and
      mechanical supporters are also available using the CNT-polymer composite. The
      preliminary fabrication results demonstrate a flexible capacitive sensor with 50
      MUm high CNT interdigitated electrodes on a poly-dimethylsiloxane substrate. The
      tests show that the typical capacitance change is several dozens of fF and the
      gauge factor is in the range of 3.44-4.88 for strain and bending curvature
      measurement; the sensitivity of the tactile sensor is 1.11% N(-1); a proximity
      distance near 2 mm away from the sensor can be detected.

PMID- 24113136
TI  - Diversity of trypanosomatids (Kinetoplastea: Trypanosomatidae) parasitizing fleas
      (Insecta: Siphonaptera) and description of a new genus Blechomonas gen. n.
AB  - To further investigate the diversity of Trypanosomatidae we have examined the
      species present within the flea (Siphonaptera) population in the Czech Republic.
      Out of 1549 fleas, 239 were found to be infected by trypanosomatids. Axenic
      cultures were established from 90 infected specimens and 29 of them were further
      characterized. Molecular phylogenetic analysis of the SL RNA, gGAPDH, and SSU
      rRNA genes revealed a striking diversity within this group and analyzed isolates
      were classified into 16 Typing units (TUs) of which 15 typified new species. In
      addition to one Trypanosoma species, two TUs grouped within the sub-family
      Leishmaniinae, two clustered together with Herpetomonas, wheras 11 TUs formed a
      novel clade branching off between Trypanosoma spp. and remaining trypanosomatids.
      We propose to recognize this clade as a new genus Blechomonas and a new subfamily
      Blechomonadinae, and provide molecular and morphological description of 11 TUs
      representing this genus. Our finding of such an ancient host-specific group sheds
      new light at the origin of Trypanosomatidae and the roots of dixenous parasitism.
      The strict host restriction of Blechomonas to Siphonaptera with adult fleas'
      dependence on blood meal may reflect passing of parasites from larvae through
      pupae to adults and implies potential transmission to the warm-blooded
      vertebrates. 

PMID- 24113137
TI  - Attitudes of U.K. breast and plastic surgeons to lipomodelling in breast surgery.
AB  - Lipomodelling is increasingly popular in breast surgery. The aims of this study
      were to elucidate the prevalence and practice of lipomodelling by surgeons in the
      UK and explore their attitudes and reservations to the technique. METHODOLOGY: A
      study specific questionnaire was circulated to Breast and Plastic Surgeons with
      an interest in breast reconstruction. RESULTS: 228 surgeons responded.
      Lipomodelling in breast surgery was performed by 48/70 (69%) plastic surgeons and
      17/158 (11%) breast surgeons (p < 0.0001). Most attitudes were positive with over
      60% surgeons agreeing that the benefits of lipomodelling outweighed the risks.
      Critics cited the lack of prospective, long term follow up data (16%) in addition
      to oncological (4%), radiological (8%) and efficacy (4%) concerns. CONCLUSIONS:
      Lipomodelling is performed by the majority of plastic surgeons who responded.
      Despite oncological, radiological and efficacy concerns, the majority of surgeons
      feel that the benefits of lipomodelling in the breast outweigh the risks.

PMID- 24113138
TI  - Fms-like tyrosine kinase 3 ligand-dependent dendritic cells in autoimmune
      inflammation.
AB  - Dendritic cells (DCs) are specialized in capture, processing and presentation of
      antigens to T cells. Depending on the type of DC and its activation state, the
      interaction of DCs with naive T cells can lead to different types of immune
      response, or to T-cell tolerance. The existence of many specialized subtypes of
      DCs with particular functions has raised the need to distinguish DCs formed in
      steady-state from those produced during an inflammatory response. In patients
      with autoimmune disease and in experimental animal models of autoimmunity, DCs
      show abnormalities in both numbers and activation state, expressing immunogenic
      levels of co-stimulatory molecules and pro-inflammatory cytokines. Initial in
      vitro studies of cytokines in DC development revealed distinct and important
      roles for the receptor tyrosine kinases, granulocyte-macrophage colony
      stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF, also
      called CSF1) and fms-like tyrosine kinase 3 ligand (Flt3L) in the generation of
      DCs. Flt3L is critical for instructing DC generation throughout different organs
      and regulates DC development from Flt3(+) lymphoid and myeloid-committed
      progenitors to DCs in vivo. The aim of this review is to provide an overview of
      the role of Flt3L-dependent DCs in the immunopathogenesis of autoimmunity and
      chronic inflammation and its potential as therapeutic targets. 

PMID- 24113139
TI  - Phage lysis: do we have the hole story yet?
AB  - In infections of Gram-negative bacteria, lysis is a three step process, with a
      choice of two effectors for each step. At a precise, allele-specific time, the
      inner membrane (IM) is fatally permeabilized by either a holin or a pinholin.
      This allows a muralytic enzyme, either a canonical endolysin, escaping from the
      cytoplasm, or a SAR endolysin, activated in the periplasm, to degrade the
      peptidoglycan. Surprisingly, a third class of lysis protein, the spanin, is
      required for disruption of the outer membrane (OM). Key steps are regulated by
      membrane protein dynamics, both in terms of bilayer topology and subcellular
      distribution, by the energization of the membrane, and by holin-specific
      inhibitors called antiholins. 

PMID- 24113141
TI  - Immediate and delayed effects of mammographic screening on breast cancer
      mortality and incidence in birth cohorts.
AB  - BACKGROUND: Trend studies investigating the impact of mammographic screening
      usually display age-specific mortality and incidence rates over time, resulting
      in an underestimate of the benefit of screening, that is, mortality reduction,
      and an overestimate of its major harmful effect, that is, overdiagnosis. This
      study proposes a more appropriate way of analysing trends. METHODS: Breast cancer
      mortality (1950-2009) and incidence data (1975-2009) were obtained from
      Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer
      Registry in the Netherlands for women aged 25-85 years. Data were visualised in
      age-birth cohort and age-period figures. RESULTS: Birth cohorts invited to
      participate in the mammographic screening programme showed a deflection in the
      breast cancer mortality rates within the first 5 years after invitation.
      Thereafter, the mortality rate increased, although less rapidly than in uninvited
      birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in
      invasive breast cancer incidence rate during the first 5 years of invitation,
      followed by a moderate increase during the following screening years and a
      decline after passing the upper age limit. CONCLUSION: When applying a trend
      study to estimate the impact of mammographic screening, we recommend using a
      birth cohort approach.

PMID- 24113140
TI  - Repair kinetics of acrolein- and (E)-4-hydroxy-2-nonenal-derived DNA adducts in
      human colon cell extracts.
AB  - omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) play a role in the
      pathogenesis of colon cancer. Upon oxidation, PUFAs generate alpha,beta
      unsaturated aldehydes or enals, such as acrolein (Acr) and (E)-4-hydroxy-2
      nonenal (HNE), which can form cyclic adducts of deoxyguanosine (Acr-dG and HNE
      dG, respectively) in DNA. Both Acr-dG and HNE-dG adducts have been detected in
      human and animal tissues and are potentially mutagenic and carcinogenic. In vivo
      levels of Acr-dG in DNA are at least two orders of magnitude higher than those of
      HNE-dG. In addition to the facile reaction with Acr, the higher levels of Acr-dG
      than HNE-dG in vivo may be due to a lower rate of repair. Previous studies have
      shown that HNE-dG adducts are repaired by the NER pathway (Choudhury et al.
      [42]). We hypothesize that Acr-dG adducts are repaired at a slower rate than HNE
      dG and that HNE-dG in DNA may influence the repair of Acr-dG. In this study,
      using a DNA repair synthesis assay and a LC-MS/MS method, we showed that Acr-dG
      in a plasmid DNA is repaired by NER proteins, but it is repaired at a much slower
      rate than HNE-dG in human colon cell extracts, and the slow repair of Acr-dG is
      likely due to poor recognition/excision of the lesions in DNA. Furthermore, using
      a plasmid DNA containing both adducts we found the repair of Acr-dG is
      significantly inhibited by HNE-dG, however, the repair of HNE-dG is not much
      affected by Acr-dG. This study demonstrates that the NER repair efficiencies of
      the two major structurally-related in vivo cyclic DNA adducts from lipid
      oxidation vary greatly. More importantly, the repair of Acr-dG can be
      significantly retarded by the presence of HNE-dG in DNA. Therefore, this study
      provides a mechanistic explanation for the higher levels of Acr-dG than HNE-dG
      observed in tissue DNA. 

PMID- 24113142
TI  - A microRNA-based prediction algorithm for diagnosis of non-small lung cell
      carcinoma in minimal biopsy material.
AB  - BACKGROUND: Diagnosis is jeopardised when limited biopsy material is available or
      histological quality compromised. Here we developed and validated a prediction
      algorithm based on microRNA (miRNA) expression that can assist clinical diagnosis
      of lung cancer in minimal biopsy material to improve clinical management.
      METHODS: Discovery utilised Taqman Low Density Arrays (754 miRNAs) in 20 non
      small cell lung cancer (NSCLC) tumour/normal pairs. In an independent set of 40
      NSCLC patients, 28 miRNA targets were validated using qRT-PCR. A prediction
      algorithm based on eight miRNA targets was validated blindly in a third
      independent set of 47 NSCLC patients. The panel was also tested in formalin-fixed
      paraffin-embedded (FFPE) specimens from 20 NSCLC patients. The genomic
      methylation status of highly deregulated miRNAs was investigated by
      pyrosequencing. RESULTS: In the final, frozen validation set the panel had very
      high sensitivity (97.5%), specificity (96.3%) and ROC-AUC (0.99, P=10(-15)). The
      panel provided 100% sensitivity and 95% specificity in FFPE tissue (ROC-AUC=0.97
      (P=10(-6))). DNA methylation abnormalities contribute little to the deregulation
      of the miRNAs tested. CONCLUSION: The developed prediction algorithm is a
      valuable potential biomarker for assisting lung cancer diagnosis in minimal
      biopsy material. A prospective validation is required to measure the enhancement
      of diagnostic accuracy of our current clinical practice.

PMID- 24113143
TI  - The potential contribution of tumour-related factors to the development of FOLFOX
      induced sinusoidal obstruction syndrome.
AB  - BACKGROUND: Chemotherapy-associated liver injury (CALI) has been linked to
      increased morbidity and poorer disease-specific outcomes in patients undergoing
      resection of colorectal liver metastases (CRLM). The aim of this study was to
      assess the contribution of tumour-related factors to the development of FOLFOX
      induced liver injury. METHODS: We assessed the effect of FOLFOX treatment on the
      murine liver either in the presence or absence of CRLM to evaluate the
      contribution of both chemotherapy and tumour death to the development of CALI.
      RESULTS: In the presence of liver metastases, there was increased hepatic
      expression of plasminogen activator inhibitor-1 (146-fold; P<0.01) and vWF (2.4
      fold; P<0.01) transcript as compared with sham-operated controls. In addition, we
      detected large clusters of megakaryocytes in the spleen of FOLFOX-treated tumour
      bearing animals. The livers of FOLFOX-treated animals also showed changes in
      matrix remodelling genes such as TGFbeta (P<0.01), MMP2 (P<0.001), TIMP1
      (P<0.001) and Pro-Collagen I (P<0.05) which was exacerbated in the presence of
      tumour. These genes have previously been demonstrated to have a key role in
      FOLFOX-induced liver injury. CONCLUSION: It appears that the toxicity of FOLFOX
      chemotherapy is enhanced by tumour-related factors.

PMID- 24113144
TI  - Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U
      box protein CHIP.
AB  - Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder
      characterized by ataxia and hypogonadism. Recently, it was suggested that
      disordered ubiquitination underlies GHS though the discovery of exome mutations
      in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing
      in a family with two of three siblings afflicted with ataxia and hypogonadism and
      identified a homozygous mutation in STUB1 (NM_005861) c.737C->T, p.Thr246Met, a
      gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein).
      CHIP plays a central role in regulating protein quality control, in part through
      its ability to function as an E3 ligase. Loss of CHIP function has long been
      associated with protein misfolding and aggregation in several genetic mouse
      models of neurodegenerative disorders; however, a role for CHIP in human
      neurological disease has yet to be identified. Introduction of the Thr246Met
      mutation into CHIP results in a loss of ubiquitin ligase activity measured
      directly using recombinant proteins as well as in cell culture models. Loss of
      CHIP function in mice resulted in behavioral and reproductive impairments that
      mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss
      of-function mutation in CHIP. Our findings further highlight the role of
      disordered ubiquitination and protein quality control in the pathogenesis of
      neurodegenerative disease and demonstrate the utility of combining whole-exome
      sequencing with molecular analyses and animal models to define causal disease
      polymorphisms. 

PMID- 24113145
TI  - Left atrial size quantification using non-contrast-enhanced cardiac computed
      tomography - association with cardiovascular risk factors and gender-specific
      distribution in the general population: the Heinz Nixdorf Recall study.
AB  - BACKGROUND: Left atrial (LA) size is associated with cardiovascular mortality and
      morbidity. Once cardiac computed tomography (CT) is performed, information on LA
      size is readily available without additional contrast media or radiation
      exposure. PURPOSE: To determine the association of CT-derived LA area and body
      surface area-adjusted (BSA) LA index with cardiovascular risk factors and
      describe age- and gender-specific normative values in a general population
      cohort. MATERIAL AND METHODS: This study included 3945 participants (mean age, 59
      +/- 8 years; 53% women) from the community-based Heinz Nixdorf Recall Study. LA
      area in an axial image at the level of the mitral valve was quantified from non
      contrast-enhanced electron-beam CT by manual delineations of the boundaries of
      the LA with exclusion of subjects with prevalent cardiovascular disease.
      Definition of normative values was performed in subjects without predictors of LA
      enlargement. RESULTS: LA quantification was feasible in all subjects. Men had
      larger LA size (1856 mm(2) vs. 1677 mm(2), P < 0.0001), while after adjustment
      for BSA, this effect was inverted (910 mm(2)/m(2) vs. 933 mm(2)/m(2) for men and
      women, P < 0.0001). Determinants of body size were major predictors of LA size
      (body mass index [BMI]: R(2) = 0.195, BSA: R(2 )= 0.216, both P < 0.0001). Blood
      pressure was associated with LA size (parameter-estimate [95% confidence
      interval] = 51.0 (4.9-57.1) mm(2)/10 mmHg for systolic, 31.4 (25.4-37.4) mm(2)/5
      mmHg for diastolic blood pressure, 214.6 (186.9-242.3) mm(2) for antihypertensive
      medication, P < 0.0001 for all). Cholesterol levels, lipid-lowering therapy, and
      diabetes were associated with LA in univariable analysis, however, correlations
      were low (r(2 )<= 0.026). Current smoking was associated with reduced LA size (
      115.9 [-149.0 - -82.8] mm(2), P < 0.0001). In multivariable regression, BMI,
      blood pressure, antihypertensive medication, and smoking remained associated with
      LA size (P < 0.005). CONCLUSION: Non-contrast-enhanced cardiac CT enables LA
      quantification with body size, hypertension, and smoking status being predictors
      of LA size.

PMID- 24113146
TI  - What place for lisdexamfetamine in children and adolescents with ADHD?
AB  - Attention deficit hyperactivity disorder (ADHD) is the commonest behavioural
      disorder in the UK, affecting 2-5% of school-aged children and young people.(1)
      Guidelines from the National Institute for Health and Care Excellence (NICE)
      state that medication is not indicated as first-line treatment for school-age
      children and young people with ADHD, but should be reserved for those with severe
      symptoms and impairment, or those with moderate levels of impairment who have
      refused non-drug interventions, or those whose symptoms have not responded
      sufficiently to parent-training/education programmes or group psychological
      treatment.(2) Current drug options include methylphenidate (first-line),
      atomoxetine (first- or second-line) or dexamfetamine (second- or third-line).(2)
      Lisdexamfetamine (Elvanse-Shire Pharmaceuticals) is a prodrug of dexamfetamine,
      licensed as part of a comprehensive treatment programme for ADHD in children aged
      6 years and over when response to previous methylphenidate treatment is
      considered clinically inadequate.(3,4) Here we review the place of
      lisdexamfetamine in the management of ADHD in children and adolescents.

PMID- 24113147
TI  - Understanding systematic reviews and meta-analyses.
AB  - Systematic reviews and meta-analyses of randomised controlled trials are
      increasingly being used by healthcare professionals, policy makers, budget
      holders and patients to inform decisions relating to the effectiveness of
      competing interventions or healthcare delivery programmes. Well-conducted
      systematic reviews can help to address the challenge presented by the ever
      increasing volume of original research.1 In 2009, DTB published an article that
      introduced the basic concepts relating to systematic reviews and meta-analyses.2
      In this article we build on our original article and take a more detailed look at
      what a reader should be aware of when reading a systematic review to ensure that
      the appropriate techniques have been used. 

PMID- 24113150
TI  - Improved atomic force microscope infrared spectroscopy for rapid nanometer-scale
      chemical identification.
AB  - Atomic force microscope infrared spectroscopy (AFM-IR) can perform IR
      spectroscopic chemical identification with sub-100 nm spatial resolution, but is
      relatively slow due to its low signal-to-noise ratio (SNR). In AFM-IR, tunable IR
      laser light is incident upon a sample, which results in a rise in temperature and
      thermomechanical expansion of the sample. An AFM tip in contact with the sample
      senses this nanometer-scale photothermal expansion. The tip motion induces
      cantilever vibrations, which are measured either in terms of the peak-to-peak
      amplitude of time-domain data or the integrated magnitude of frequency-domain
      data. Using a continuous Morlet wavelet transform to the cantilever dynamic
      response, we show that the cantilever dynamics during AFM-IR vary as a function
      of both time and frequency. Based on the observed cantilever response, we tailor
      a time-frequency-domain filter to identify the region of highest vibrational
      energy. This approach can increase the SNR of the AFM cantilever signal, such
      that the throughput is increased 32-fold compared to state-of-the art procedures.
      We further demonstrate significant increases in AFM-IR imaging speed and chemical
      identification of nanometer-scale domains in polymer films.

PMID- 24113148
TI  - Pharmacokinetic assessment of efflux transport in sunitinib distribution to the
      brain.
AB  - This study quantitatively assessed transport mechanisms that limit the brain
      distribution of sunitinib and investigated adjuvant strategies to improve its
      brain delivery for the treatment of glioblastoma multiforme (GBM). Sunitinib has
      not shown significant activity in GBM clinical trials, despite positive results
      seen in preclinical xenograft studies. We performed in vivo studies in transgenic
      Friend leukemia virus strain B mice: wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and
      Mdr1a/b(-/-)Bcrp1(-/-) genotypes were examined. The brain-to-plasma area under
      the curve ratio after an oral dose (20 mg/kg) was similar to the steady-state
      tissue distribution coefficient, indicating linear distribution kinetics in mice
      over this concentration range. Furthermore, the distribution of sunitinib to the
      brain increased after administration of selective P-glycoprotein (P-gp) or breast
      cancer resistance protein (Bcrp) pharmacological inhibitors and a dual inhibitor,
      elacridar, comparable to that of the corresponding transgenic genotype. The brain
      to-plasma ratio after coadministration of elacridar in wild-type mice was ~ 12
      compared with ~ 17.3 in Mdr1a/b(-/-)Bcrp1(-/-) mice. Overall, these findings
      indicate that there is a cooperation at the blood-brain barrier (BBB) in
      restricting the brain penetration of sunitinib, and brain delivery can be
      enhanced by administration of a dual inhibitor. These data indicate that the
      presence of cooperative efflux transporters, P-gp and Bcrp, in an intact BBB can
      protect invasive glioma cells from chemotherapy. Thus, one may consider the use
      of transporter inhibition as a powerful adjuvant in the design of future clinical
      trials for the targeted delivery of sunitinib in GBM.

PMID- 24113149
TI  - Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal
      metabolic status.
AB  - In utero environmental perturbations have been associated with epigenetic changes
      in the offspring and a lifelong susceptibility to cardiovascular diseases (CVD).
      DNA methylation at the ATP-binding cassette transporter A1 (ABCA1) gene was
      previously associated with CVD, but whether these epigenetic marks respond to
      changes in the maternal environment is unknown. This study was undertaken to
      assess the associations between the maternal metabolic profile and ABCA1 DNA
      methylation levels in placenta and cord blood. Placenta and cord blood samples
      were obtained at delivery from 100 women including 26 with impaired glucose
      tolerance (IGT) diagnosed following a 75 g-oral glucose tolerance test (OGTT)
      between week 24 and 28 of gestation. ABCA1 DNA methylation and mRNA levels were
      measured using bisulfite pyrosequencing and quantitative real-time PCR,
      respectively. We report that ABCA1 DNA methylation levels on the maternal side of
      the placenta are correlated with maternal high density lipoprotein cholesterol
      (HDL-C) levels (r<-0.21; P<0.04) and glucose levels 2 h post-OGTT (r = 0.25; P =
      0.02). On the fetal side of the placenta, ABCA1 DNA methylation levels are
      associated with cord blood triglyceride levels (r = -0.28; P = 0.01). ABCA1 DNA
      methylation variability on both sides of the placenta are also associated with
      ABCA1 mRNA levels (r<-0.35; P = 0.05). As opposed to placenta, cord blood DNA
      methylation levels are negatively correlated with maternal glucose 2 h post-OGTT
      (r = -0.26; P = 0.02). In conclusion, the epivariations observed in placenta and
      cord blood likely contribute to an optimal materno-fetal cholesterol transfer.
      These in utero epigenetics adaptations may also potentially trigger the long-term
      susceptibility of the newborn to dyslipidemia and CVD. 

PMID- 24113151
TI  - Primary progressive dynamic aphasia and Parkinsonism: generation, selection and
      sequencing deficits.
AB  - MC is the first reported case of dynamic aphasia in the context of non-fluent
      progressive aphasia and Parkinson's disease. MC's language profile was
      characterised by the hallmark propositional language impairment despite well
      preserved naming, reading, repetition and comprehension skills. The severity of
      MC's propositional language deficit was comparable to other dynamic aphasic
      patients. Word and sentence generation performance was severely impaired only
      when many competing responses were activated by a stimulus. Thus, when a dominant
      response was available verbal generation was satisfactory. MC also presented with
      a deficit in idea generation and fluent sequencing of novel thoughts as discourse
      generation was extremely reduced and perseverative. In addition, non-verbal
      generation was impaired although dissociations emerged. MC was able to generate
      novel designs and gestures but his performance was highly perseverative, and his
      motor movement selection was abnormal, resembling a non-random pattern. MC is the
      first dynamic aphasic case with concurrent deficits in three mechanisms thought
      crucial for conceptual preparation processes; namely impaired selection, impaired
      generation of ideas and impaired fluent sequencing of novel thoughts. The
      findings are discussed in relation to conceptual preparation processes and their
      organisation, accounts of dynamic aphasia and the roles of the left inferior
      frontal and basal ganglia regions in conceptual preparation processes for verbal
      and non-verbal generation. 

PMID- 24113152
TI  - Effects of electroacupuncture on stress-related symptoms in medical students: a
      randomised placebo-controlled study.
AB  - OBJECTIVE: To assess the effects of electroacupuncture (EA) on relieving stress
      related symptoms-sleep disorders, anxiety, depression and burnout-in medical
      students. METHODS: Eighty-two students were randomised into an EA treatment group
      (n=30), a sham TENS group (n=18) and an untreated control group (n=34). EA was
      applied at a continuous frequency of 2 Hz to the limbs, face, ears and scalp for
      20 min once a week, over 6-8 weeks. Sham transcutaneous electrical nerve
      stimulation (TENS) was performed on similar sites for the same number of times in
      each session and for the same length of time. Outcome measurements included a
      comparison of the indices obtained by different self-applied questionnaires
      before and after treatment. The surveys used were the Mini-Sleep Questionnaire
      (MSQ), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the
      Beck Depression and Anxiety Inventories (BDI and BAI) and the Maslach Burnout
      Inventory-Student Survey (MBI-SS), in addition to the Quality of Life
      Questionnaire-abbreviated version (WHOQOL-bref). RESULTS: EA significantly
      improved scores on the MSQ, PSQI, BDI and the cynicism and academic efficacy (AE)
      dimensions of the MBI-SS in relation to the control. Sleep quality (MSQ) improved
      from 36.9 (SD 7.6) to 25.0 (5.7) with EA, 37.6 (6.0) to 32.1 (6.9) with sham
      TENS, and 36.5 (5.9) to 33.6 (6.7) in the controls (p=0.0000). Compared with the
      sham TENS group, EA significantly reduced scores on the PSQI. Score improvements
      in the sham TENS group in relation to control group were significant in the MSQ,
      BDI and AE. In the EA group, the number of students with better scores after
      intervention was significantly higher for the MSQ, PSQI, ESS and BAI. This only
      occurred for the MSQ in the sham TENS group and for the MSQ and ESS in the
      control group. CONCLUSIONS: EA significantly reduced stress-related mental
      symptoms. The improvement obtained by sham TENS compared with the control group
      confirmed the presence of a placebo effect resulting from the treatment ritual.

PMID- 24113153
TI  - Oxidative 1,2-difunctionalization of activated alkenes with benzylic C(sp3)-H
      bonds and aryl C(sp2)-H bonds.
AB  - DTBP (di-tert-butyl peroxide) is utilized to mediate oxidative 1,2
      difunctionalization of activated alkenes with an aryl C(sp(2))-H bond and a
      benzylic C(sp(3))-H bond for the synthesis of functionalized oxindoles. This
      reaction is a new organomediated strategy for alkene difunctionalization
      facilitated by Lewis acids. 

PMID- 24113154
TI  - Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish
      cohort of older adults.
AB  - BACKGROUND: Vitamin E includes eight natural antioxidant compounds (four
      tocopherols and four tocotrienols), but alpha-tocopherol has been the main focus
      of investigation in studies of cognitive impairment and Alzheimer's disease.
      OBJECTIVE: To investigate the association between serum levels of tocopherols and
      tocotrienols, markers of vitamin E oxidative/nitrosative damage (alpha
      tocopherylquinone, 5-nitro-gamma-tocopherol) and incidence of cognitive
      impairment in a population-based study. DESIGN: A sample of 140 non-cognitively
      impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging,
      and Dementia (CAIDE) study was followed-up for 8years to detect cognitive
      impairment, defined as development of mild cognitive impairment (MCI) or
      Alzheimer's dementia. The association between baseline serum vitamin E and
      cognitive impairment was analyzed with multiple logistic regression after
      adjusting for several confounders. RESULTS: The risk of cognitive impairment was
      lower in subjects in the middle tertile of the gamma-tocopherol/cholesterol ratio
      than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95%
      confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive
      impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest
      [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-gamma-tocopherol/gamma
      tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower
      risk of cognitive impairment in subjects with higher levels of gamma-tocopherol,
      beta-tocotrienol, and total tocotrienols. CONCLUSIONS: Elevated levels of
      tocopherol and tocotrienol forms are associated with reduced risk of cognitive
      impairment in older adults. The association is modulated by concurrent
      cholesterol concentration. Various vitamin E forms might play a role in cognitive
      impairment, and their evaluation can provide a more accurate measure of vitamin E
      status in humans.

PMID- 24113155
TI  - Placental autophagy regulation by the BOK-MCL1 rheostat.
AB  - Autophagy is the catabolic degradation of cellular cytoplasmic constituents via
      the lysosomal pathway that physiologically elicits a primarily cytoprotective
      function, but can rapidly be upregulated in response to stressors thereby
      inducing cell death. We have reported that the balance between the BCL2 family
      proteins BOK and MCL1 regulates human trophoblast cell fate and its alteration
      toward cell death typifies preeclampsia. Here we demonstrate that BOK is a potent
      inducer of autophagy as shown by increased LC3B-II production, autophagosomal
      formation and lysosomal activation in HEK 293. In contrast, using JEG3 cells we
      showed that prosurvival MCL1 acts as a repressor of autophagy via an interaction
      with BECN1, which is abrogated by BOK. We found that MCL1-cleaved products,
      specifically MCL1c157, trigger autophagy while the splicing variant MCL1S has no
      effect. Treatment of JEG3 cells with nitric oxide donor SNP resulted in BOK-MCL1
      rheostat dysregulation, favoring BOK accumulation, thereby inducing autophagy.
      Overexpression of MCL1 rescued oxidative stress-induced autophagy. Of clinical
      relevance, we report aberrant autophagy levels in the preeclamptic placenta due
      to impaired recruitment of BECN1 to MCL1. Our data provided the first evidence
      for a key role of the BOK-MCL1 system in regulating autophagy in the human
      placenta, whereby an adverse environment as seen in preeclampsia tilts the BOK
      MCL1 balance toward the build-up of isoforms that triggers placental autophagy. 

PMID- 24113156
TI  - Food choking hazards in children.
AB  - OBJECTIVES: To review the literature on pediatric food choking risks, with the
      long-term goal of supporting legislation regulating the production, labeling, and
      distribution of high-risk foods. METHODS: A PubMed search (Keywords: choking,
      obstruction, asphyxiation, foreign body, food) was conducted in July-September
      2010 with publication dates ranging from 1966 to 2010. STUDY SELECTION: Articles
      related to pediatric foreign body aspiration (FBA) were selected by three
      independent reviewers. 1145 articles were initially identified. Abstracts were
      then screened utilizing a tool designed to isolate relevant pediatric choking
      events; this tool helped to only select abstracts which presented data on
      patients younger than 18 years of age who had choked on food items. Through this,
      a total of 72 pertinent articles were isolated (55 observational studies, 17 case
      reports/series). DATA EXTRACTION: For each study, patient age, sex, foreign body
      location, presenting signs and symptoms, utility of radiographic studies, and
      type of foreign body detected in the majority of study participants were
      determined. A "majority" of patients for each study was predetermined arbitrarily
      to be 2/3 of the studied population. RESULTS: The majority of patients in each
      observational study was determined to be: male (87% of all studies) and age <5
      years (95% of all studies). Aspirated foreign bodies were mostly detected in the
      right main bronchus foreign body (72% of all studies), and there were abnormal
      radiographic signs (81% of all studies) at the time of evaluation. Food-object
      foreign bodies were the most frequent factors associated with choking (94% of all
      studies). CONCLUSION: Childhood aspiration of food-objects is a significant
      public health issue. Although there is substantial legislation regulating non
      food items that pose a choking hazard, equivalent guidelines do not exist for
      high-risk foods. Our study identifies and confirms several risk factors for
      pediatric FBA events. In doing so, it echoes the concerns and suggestions of
      various groups in supporting the development of legislation which may reduce the
      incidence of food-object aspiration.

PMID- 24113157
TI  - TACRD and VACTERL associations in a fetus: case report and review of the
      literature.
AB  - Tracheal agenesis is a rare and potentially lethal congenital anomaly. The
      incidence is less than 1/50,000, with a male:female ratio of 2:1. We report the
      case of a male fetus with complete agenesis of the trachea and a
      tracheoesophageal fistula arising from the esophagus that connected through the
      carina, as well as several abnormalities (congenital cardiac abnormalities,
      duodenal atresia, vertebral defects, anal atresia, renal defects, limb defects,
      and diaphragmatic hernia). To our knowledge, few cases of infants with VACTERL or
      TACRD association have been reported to date. Here, we report a new case of a
      fetus that showed the full range of VACTERL and TACRD associations. 

PMID- 24113158
TI  - A study of the role of different forms of chronic rhinitis in the development of
      otitis media with effusion in children affected by adenoid hypertrophy.
AB  - OBJECTIVE: The aim of the present study was to evaluate the role of the different
      forms of chronic rhinitis in the pathogenesis of otitis media with effusion in
      children affected by obstructive adenoid hypertrophy. METHODS: 81 patients, aged
      between 4 and 15 years (mean age of 6.9 years), affected by obstructive adenoid
      hypertrophy were evaluated. All patients underwent accurate history taking,
      physical examination with endoscopy of the nasopharynx, skin prick test, nasal
      cytology and hearing evaluation. RESULTS: Nasal citology showed that 21% of
      patients had a non-allergic rhinitis (NAR) subtype, 17.4% NAR overlapping with
      infectious rhinitis (IR), 29.6% IR, 4.9% allergic rhinitis (AR), 2.5% AR
      overlapping with IR and the remaining 24.6% a negative cytology. The presence of
      OME was positively correlated with neutrophils (p = 0.01) and mast cells (p =
      0.022), while it was negatively correlated with the presence of eosinophils (p =
      0.02) and bacteria (p = 0.02). CONCLUSIONS: A chronic rhinitis was present in
      more than 70% of children with AH and 60% of them showed OME. Nasal cytology
      together with SPT showed that AR was rarely present in this group of children,
      while the mast-cells and neutrophils positively correlated with OME.

PMID- 24113159
TI  - Pituitary apoplexy associated with cabergoline therapy.
AB  - Pituitary apoplexy is a rare medical emergency which results from hemorrhage or
      infarction in the pituitary gland. One of the predisposing factors is treatment
      with dopamine agonists, especially bromocriptine. We report a 20-year-old Chinese
      man with prolactinoma who developed pituitary apoplexy 6 weeks after initiation
      of cabergoline. He was treated conservatively with supportive therapy, and
      recovered well with no loss of pituitary function. A literature search was
      conducted and a review of the reported patients with pituitary apoplexy during
      treatment with dopamine agonists is discussed.

PMID- 24113160
TI  - Intraoperative aneurysmal subarachnoid hemorrhage after rupture of a previously
      undiagnosed intracranial aneurysm during Chiari decompression.
AB  - A type I Chiari malformation occurs when caudal displacement of the cerebellar
      tonsils below the level of the foramen magnum obstructs the normal flow of
      cerebrospinal fluid (CSF) between the cranial and spinal spaces, a condition that
      often needs surgical decompression to restore normal CSF circulation. Abrupt
      changes in CSF flow dynamics after Chiari decompression can affect the
      intracranial CSF dynamics to the extent that a previously undiagnosed
      intracranial aneurysm remote from the site can rupture. The authors describe the
      development of an intraoperative aneurysmal subarachnoid hemorrhage that occurred
      as a result of spontaneous rupture of a previously undiagnosed right distal
      posterior inferior cerebellar artery in a 57-year-old woman with type I Chiari
      malformation who was undergoing surgical decompression. The mechanism of the
      aneurysmal rupture appears to be related to the changes of CSF flow dynamics
      during surgical decompression. Normally, pressure equilibrium between the two
      sides of the aneurysmal wall prevents its rupture, but factors that significantly
      affect this equilibrium, such as systemic hypertension, can cause the aneurysm to
      rupture. To our knowledge, the concept of spontaneous intraoperative rupture of
      intracranial aneurysm remote from the site of surgery has been described twice
      previously but under different scenarios. This scenario, to our knowledge, has
      not been previously described. 

PMID- 24113162
TI  - Cyber support: describing concerns of caregivers of people with pulmonary
      hypertension.
AB  - The purpose of this study was to gain an understanding of how caregivers of
      people with pulmonary hypertension are using an online discussion board. The
      chronicity and complex medical needs of people with pulmonary hypertension
      warrant a holistic nursing approach combining the patient and caregiver concerns
      to adequately address their needs. A qualitative descriptive approach was
      utilized. A convenience sample over an 18-month period of those caregivers who
      posted Internet messages to the Pulmonary Hypertension Discussion Board was
      included. Sociodemographics collected were age and gender of the person with
      pulmonary hypertension and the relationship of the caregiver to the person with
      pulmonary hypertension. Clinical variables collected were medications and oxygen
      use and years since diagnosis. Thematic analysis was used to identify themes. A
      total of 98 caregivers posted to the discussion board during the 18-month period;
      46% of those posting were mothers of children with pulmonary hypertension. Four
      themes emerged: fear and frustration, questions and concerns, someone to listen
      to, and moving on with life. These themes characterize how caregivers of people
      with pulmonary hypertension were using the discussion board. Caregivers of people
      with pulmonary hypertension may need more information and support from their
      healthcare providers to adequately care for those with pulmonary hypertension. 

PMID- 24113163
TI  - Research methodology for real-time stress assessment of nurses.
AB  - This article presents a research methodology for analysis of stress effects and
      allostatic load of nurses during daily activities. Stress-related health issues
      are critical in healthcare workers, in particular nurses. Typical causes of
      stress include inadequate staffing of nurses for the number and acuity of
      patients, dealing with difficult patients and families, and lack of autonomy in
      care delivery decisions. This is all compounded by lack of recovery time while on
      shift, variable shifts with limited recovery time between days worked, and
      fatigue from dealing with difficult patients, families, and healthcare workers.
      Under unresolved stress, the heart rate and other vital parameters may fail to
      return to the baseline. This study examined the physiological responses of nurses
      during care on a high-fidelity patient simulation to develop a research
      methodology and identify physiological parameters suitable for real-time
      assessment of allostatic load during work. Our results demonstrated that heart
      rate and heart rate variability can be reliably measured using wearable sensors
      to assess allostatic load. During this study and our previous related work, we
      acquired valuable experience regarding selection and deployment of commercially
      available sensors, system integration, recruitment of subjects, and general
      research methodology. The research methodology developed and presented in this
      article can be applied to a number of other applications and experimental
      protocols. 

PMID- 24113161
TI  - Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential
      of cells by activating the CREB pathway.
AB  - Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in
      human tissues, which catalyzes the formation of cyclic adenosine-3',5'
      monophosphate (cAMP). However, our transcriptome analysis of gastric cancer
      tissue samples (NCBI GEO GSE30727) revealed that ADCY3 expression was
      specifically altered in cancer samples. Here we investigated the tumor-promoting
      effects of ADCY3 overexpression and confirmed a significant correlation between
      the upregulation of ADCY3 and Lauren's intestinal-type gastric cancers. ADCY3
      overexpression increased cell migration, invasion, proliferation, and
      clonogenicity in HEK293 cells; conversely, silencing ADCY3 expression in SNU-216
      cells reduced these phenotypes. Interestingly, ADCY3 overexpression increased
      both the mRNA level and activity of matrix metalloproteinase 2 (MMP2) and MMP9 by
      increasing the levels of cAMP and phosphorylated cAMP-responsive element-binding
      protein (CREB). Consistent with these findings, treatment with a protein kinase A
      (PKA) inhibitor decreased MMP2 and MMP9 expression levels in ADCY3-overexpressing
      cells. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer
      cells suppressed tumor growth in a tumor xenograft model. Thus, ADCY3
      overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB
      pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region revealed
      that gene expression was reduced by hypermethylation of CpG sites, and increased
      by 5-Aza-2'-deoxycytidine (5-Aza-dC)-induced demethylation. Our study is the
      first to report an association of ADCY3 with gastric cancer as well as its
      tumorigenic potentials. In addition, we demonstrate that the expression of ADCY3
      is regulated through an epigenetic mechanism. Further study on the mechanism of
      ADCY3 in tumorigenesis will provide the basis as a new molecular target of
      gastric cancer. 

PMID- 24113164
TI  - Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in
      cervical cancer cells.
AB  - Cancer cells often develop drug resistance. In cisplatin-resistant HeLa cisR
      cells, fibroblast growth factor 13 (FGF13/FHF2) gene and protein expression was
      strongly upregulated, and intracellular platinum concentrations were kept low.
      When the FGF13 expression was suppressed, both the cells' resistance to platinum
      drugs and their ability to keep intracellular platinum low were abolished.
      Overexpression of FGF13 in parent cells led to greater resistance to cisplatin
      and reductions in the intracellular platinum concentration. These cisplatin
      resistant cells also showed increased resistance to copper. In preoperative
      cervical cancer biopsy samples from poor prognoses patients after cisplatin
      chemoradiotherapy, FGF13-positive cells were detected more abundantly than in the
      biopsy samples from patients with good prognoses. These results suggest that
      FGF13 plays a pivotal role in mediating resistance to platinum drugs, possibly
      via a mechanism shared by platinum and copper. Our results point to FGF13 as a
      novel target and useful prognostic guide for cancer therapy. 

PMID- 24113165
TI  - Transcription patterns of genes encoding four metallothionein homologs in Daphnia
      pulex exposed to copper and cadmium are time- and homolog-dependent.
AB  - Metallothioneins are proteins that play an essential role in metal homeostasis
      and detoxification in nearly all organisms studied to date. Yet discrepancies
      between outcomes of chronic and acute exposure experiments hamper the
      understanding of the regulatory mechanisms of their isoforms following metal
      exposure. Here, we investigated transcriptional differences among four identified
      homologs (mt1-mt4) in Daphnia pulex exposed across time to copper and cadmium
      relative to a control. Transcriptional upregulation of mt1 and mt3 was detected
      on day four following exposure to cadmium, whereas that of mt2 and mt4 was
      detected on day two and day eight following exposure to copper. These results
      confirm temporal and metal-specific differences in the transcriptional induction
      of genes encoding metallothionein homologs upon metal exposure which should be
      considered in ecotoxicological monitoring programs of metal-contaminated water
      bodies. Indeed, the mRNA expression patterns observed here illustrate the complex
      regulatory system associated with metallothioneins, as these patterns are not
      only dependent on the metal, but also on exposure time and the homolog studied.
      Further phylogenetic analysis and analysis of regulatory elements in upstream
      promoter regions revealed a high degree of similarity between metallothionein
      genes of Daphnia pulex and Daphnia magna, a species belonging to the same genus.
      These findings, combined with a limited amount of available expression data for
      D. magna metallothionein genes, tentatively suggest a potential generalization of
      the metallothionein response system between these Daphnia species. 

PMID- 24113166
TI  - Evaluation of toxicity and oxidative stress induced by copper oxide nanoparticles
      in the green alga Chlamydomonas reinhardtii.
AB  - Copper oxide nanoparticles (CuO NP) are frequently employed for their
      antimicrobial properties in antifouling paints. Their extensive use can
      contaminate aquatic ecosystems. However, the toxicological effects of this NP in
      the environment are poorly known. In this study, we evaluated the toxicity and
      oxidative stress induced by CuO NP on Chlamydomonas reinhardtii using several
      toxicological assays. CuO NP was found to induce growth inhibition and a
      significant decrease in carotenoids levels. From data on cells density after 72 h
      of CuO NP exposure in light, the EC50 value was calculated to be 150.45+/-1.17 mg
      L(-1) and the NOEC<=100 mg L(-1). Evaluation of esterase activity demonstrates a
      decrease in cell metabolism activity with the increase of CuO NP concentration.
      The CuO NP induced an increase of reactive species level (190+/-0.45% at 1000 mg
      L(-1) after 72 h of exposition, compared to control) and lipid peroxidation of
      cellular membranes (73+/-2% at 1000 mg L(-1) of CuO NP in 72 h of exposition,
      compared to control). Investigation of CuO NP uptake showed the presence of NP
      into C. reinhardtii cells in different sites of the cell and, biomarkers of
      enzymatic antioxidants showed a change of activity after CuO NP exposition. In
      conclusion, C. reinhardtii was shown to be sensitive to the presence of CuO NP in
      their environment and CuO NP treatments induced a toxic response from 0.1 mg L(
      1) after 72 h of treatment.

PMID- 24113167
TI  - The p53 protein and its molecular network: modelling a missing link between DNA
      damage and cell fate.
AB  - Various molecular pharmacokinetic-pharmacodynamic (PK-PD) models have been
      proposed in the last decades to represent and predict drug effects in anticancer
      chemotherapies. Most of these models are cell population based since clearly
      measurable effects of drugs can be seen much more easily on populations of cells,
      healthy and tumour, than in individual cells. The actual targets of drugs are,
      however, cells themselves. The drugs in use either disrupt genome integrity by
      causing DNA strand breaks, and consequently initiate programmed cell death, or
      block cell proliferation mainly by inhibiting factors that enable cells to
      proceed from one cell cycle phase to the next through checkpoints in the cell
      division cycle. DNA damage caused by cytotoxic drugs (and also cytostatic drugs
      at high concentrations) activates, among others, the p53 protein-modulated
      signalling pathways that directly or indirectly force the cell to make a decision
      between survival and death. The paper aims to become the first-step in a larger
      scale enterprise that should bridge the gap between intracellular and population
      PK-PD models, providing oncologists with a rationale to predict and optimise the
      effects of anticancer drugs in the clinic. So far, it only sticks at describing
      p53 activation and regulation in single cells following their exposure to DNA
      damaging stress agents. We show that p53 oscillations that have been observed in
      individual cells can be reconstructed and predicted by compartmentalising
      cellular events occurring after DNA damage, either in the nucleus or in the
      cytoplasm, and by describing network interactions, using ordinary differential
      equations (ODEs), between the ATM, p53, Mdm2 and Wip1 proteins, in each
      compartment, nucleus or cytoplasm, and between the two compartments. This article
      is part of a Special Issue entitled: Computational Proteomics, Systems Biology &
      Clinical Implications. 

PMID- 24113168
TI  - Modelling the behaviour of uranium-series radionuclides in soils and plants
      taking into account seasonal variations in soil hydrology.
AB  - In a previous paper, a mathematical model for the behaviour of (79)Se in soils
      and plants was described. Subsequently, a review has been published relating to
      the behaviour of (238)U-series radionuclides in soils and plants. Here, we bring
      together those two strands of work to describe a new mathematical model of the
      behaviour of (238)U-series radionuclides entering soils in solution and their
      uptake by plants. Initial studies with the model that are reported here
      demonstrate that it is a powerful tool for exploring the behaviour of this decay
      chain or subcomponents of it in soil-plant systems under different hydrological
      regimes. In particular, it permits studies of the degree to which secular
      equilibrium assumptions are appropriate when modelling this decay chain. Further
      studies will be undertaken and reported separately examining sensitivities of
      model results to input parameter values and also applying the model to sites
      contaminated with (238)U-series radionuclides. 

PMID- 24113169
TI  - Thermally oxidized zinc oxide nanowires for use as chemical sensors.
AB  - Zinc oxide (ZnO) mat-based conductometric devices were fabricated using a thermal
      oxidation technique. A metallic zinc layer was deposited on the alumina
      transducer and then oxidized in a controlled atmosphere, in order to obtain ZnO
      nanostructures. Two different batches of sensors have been prepared, and their
      sensing performances have been evaluated towards oxidizing and reducing gases.
      Functional measurements showed very good sensing performances towards ethanol and
      acetone at 500  degrees C, and NO2 at 200  degrees C, indirectly confirming the n
      type behaviour of the material. The influence of the humidity on the response has
      been explored. In practical conditions the interference of humidity is very
      small, and could be neglected in many applications. Simultaneous measurements on
      different devices from the same batch confirm the high reproducibility of the
      response within the batch.

PMID- 24113170
TI  - The type of implicit motive enactment is modulated by sex hormones in naturally
      cycling women.
AB  - Sex hormones have been reported to dynamically modulate the expression of
      implicit motives, a concept that has previously been thought to be relatively
      stable over time. This study investigates to what extent the need for
      affiliation, power, and achievement, as well as the form of enactment of these
      needs as measured with the Operant Motive Test (OMT), is affected by cycle-phase
      dependent sex hormone fluctuations. In addition to measuring the strength of
      motive expression, the OMT also captures different forms of motive enactment. In
      an intra-subject design with repeated measures, no evidence for cycle-phase
      related variation in overall motive scores was found. However, when different
      forms of motive enactment were considered, an effect of menstrual cycle was
      observed. The incentive-based inhibition of the power motive was significantly
      reduced at the time of ovulation, compared to the menstrual and to the mid-luteal
      phase, in naturally cycling women. In women with relatively stable hormone
      concentrations (due to using hormonal contraceptives), no significant changes in
      the form of motive enactment were evident. The results indicate a specific
      hormonal influence on motive-related cognitive processes that are related to
      inhibitive processes in behavior control. 

PMID- 24113171
TI  - Gonadal status-dependent effects of in vivo beta-estradiol administration to
      female rats on in vitro epileptiform activity induced by low [Mg2+]0 in combined
      hippocampus-entorhinal cortex slices.
AB  - There are controversial data regarding estrogen effects on neuronal excitability.
      We investigated whether beta-estradiol (EB) administration to ovariectomized
      (OVX) or gonadally intact female rats alters epileptiform activity within the
      dentate gyrus network induced in vitro by removing [Mg2+]o in combined
      hippocampus-entorhinal cortex slices. In vivo EB administration significantly
      influenced the epileptiform activity in gonadal status-dependent manner. The
      onset of epileptiform discharges was modestly delayed in slices from OVX rats
      replaced with physiologically relevant doses of EB but the number of discharges
      was not affected. In contrast, EB administration to gonadally intact rats had
      robust effects such that: EB delayed the onset of discharges but significantly
      increased their number within the dentate gyrus network. Our data suggest that EB
      in physiologically relevant concentrations does not seem to negatively affect
      hippocampal neuronal excitability, nevertheless supraphysiological EB levels may
      enhance seizure severity.

PMID- 24113173
TI  - ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for
      TRAIL-induced apoptosis.
AB  - The pathways of reactive oxygen species (ROS)-mediated apoptosis induction, of
      Bax activation and the sensitization of tumor cells for TRAIL (TNF-related
      apoptosis-inducing ligand)-induced apoptosis are still largely elusive. Here,
      sensitization of melanoma cells for TRAIL by the PI3-kinase inhibitor wortmannin
      correlated to the activation of mitochondrial apoptosis pathways. Apoptosis was
      dependent on Bax and abrogated by Bcl-2 overexpression. The synergistic
      enhancement was explained by Bax activation through wortmannin, which tightly
      correlated to the characteristic Bax phosphorylation patterns. Thus, wortmannin
      resulted in early reduction of the Bax-inactivating phosphorylation at serine
      184, whereas the Bax-activating phosphorylation at threonine-167 was enhanced.
      Proving the responsibility of the pathway, comparable effects were obtained with
      an Akt inhibitor (MK-2206); while suppressed phosphorylation of serine-184 may be
      attributed to reduced Akt activity itself, the causes of enhanced threonine-167
      phosphorylation were addressed here. Characteristically, production of ROS was
      seen early in response to wortmannin and MK-2206. Providing the link between ROS
      and Bax, we show that abrogated ROS production by alpha-tocopherol or by NADPH
      oxidase 4 (NOX4) siRNA suppressed apoptosis and Bax activation. This correlated
      with reduced Bax phosphorylation at threonine-167. The data unraveled a mechanism
      by which NOX4-dependent ROS production controls apoptosis via Bax
      phosphorylation. The pathway may be considered for proapoptotic, anticancer
      strategies. 

PMID- 24113172
TI  - Autophagy and chemotherapy resistance: a promising therapeutic target for cancer
      treatment.
AB  - Induction of cell death and inhibition of cell survival are the main principles
      of cancer therapy. Resistance to chemotherapeutic agents is a major problem in
      oncology, which limits the effectiveness of anticancer drugs. A variety of
      factors contribute to drug resistance, including host factors, specific genetic
      or epigenetic alterations in the cancer cells and so on. Although various
      mechanisms by which cancer cells become resistant to anticancer drugs in the
      microenvironment have been well elucidated, how to circumvent this resistance to
      improve anticancer efficacy remains to be defined. Autophagy, an important
      homeostatic cellular recycling mechanism, is now emerging as a crucial player in
      response to metabolic and therapeutic stresses, which attempts to
      maintain/restore metabolic homeostasis through the catabolic lysis of excessive
      or unnecessary proteins and injured or aged organelles. Recently, several studies
      have shown that autophagy constitutes a potential target for cancer therapy and
      the induction of autophagy in response to therapeutics can be viewed as having a
      prodeath or a prosurvival role, which contributes to the anticancer efficacy of
      these drugs as well as drug resistance. Thus, understanding the novel function of
      autophagy may allow us to develop a promising therapeutic strategy to enhance the
      effects of chemotherapy and improve clinical outcomes in the treatment of cancer
      patients. 

PMID- 24113174
TI  - Recombinant human arginase induced caspase-dependent apoptosis and autophagy in
      non-Hodgkin's lymphoma cells.
AB  - Arginase, an arginine-degrading enzyme, has gained increased attention recently
      as a new experimental therapeutics for a variety of malignant solid cancers. In
      this study, we found that recombinant human arginase (rhArg) could induce
      remarkable growth inhibition, cell cycle arrest, and caspase-dependent apoptosis
      in Raji and Daudi non-Hodgkin's lymphoma (NHL) cells through arginine
      deprivation. Interestingly, rhArg-treatment resulted in the appearance of
      autophagosomes and upregulation of microtubule-associated protein light chain 3
      II, indicating that rhArg induced autophagy in lymphoma cells. Further study
      suggested that mammalian target of rapamycin/S6k signaling pathway may be
      involved in rhArg-induced autophagy in NHL cells. Moreover, blocking autophagy
      using pharmacological inhibitors (3-methyladenine and chloroquine) or genetic
      approaches (small interfering RNA targeting autophagy-related gene 5 and Beclin
      1) enhanced the cell killing effect of rhArg. These results demonstrated that
      rhArg has a potent anti-lymphoma activity, which could be improved by in
      combination with autophagic inhibitors, suggesting that rhArg, either alone or in
      combination with autophagic inhibitors, could be a potential novel therapeutics
      for the treatment of NHL. 

PMID- 24113175
TI  - Death receptor 6 (DR6) antagonist antibody is neuroprotective in the mouse
      SOD1G93A model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by the death of motor neurons, axon degeneration, and denervation of
      neuromuscular junctions (NMJ). Here we show that death receptor 6 (DR6) levels
      are elevated in spinal cords from post-mortem samples of human ALS and from
      SOD1(G93A) transgenic mice, and DR6 promotes motor neuron death through
      activation of the caspase 3 signaling pathway. Blocking DR6 with antagonist
      antibody 5D10 promotes motor neuron survival in vitro via activation of Akt
      phosphorylation and inhibition of the caspase 3 signaling pathway, after growth
      factor withdrawal, sodium arsenite treatment or co-culture with SOD1(G93A)
      astrocytes. Treatment of SOD1(G93A) mice at an asymptomatic stage starting on the
      age of 42 days with 5D10 protects NMJ from denervation, decreases gliosis,
      increases survival of motor neurons and CC1(+) oligodendrocytes in spinal cord,
      decreases phosphorylated neurofilament heavy chain (pNfH) levels in serum, and
      promotes motor functional improvement assessed by increased grip strength. The
      combined data provide clear evidence for neuroprotective effects of 5D10.
      Blocking DR6 function represents a new approach for the treatment of
      neurodegenerative disorders involving motor neuron death and axon degeneration,
      such as ALS. 

PMID- 24113176
TI  - IBP-mediated suppression of autophagy promotes growth and metastasis of breast
      cancer cells via activating mTORC2/Akt/FOXO3a signaling pathway.
AB  - Interferon regulatory factor-4 binding protein (IBP) is a novel upstream
      activator of Rho GTPases. Our previous studies have shown that ectopic expression
      of IBP was correlated with malignant behaviors of human breast cancer cells, and
      invasive human breast cancer had high expression of IBP that promoted the
      proliferation of these cells. However, it remains unknown whether autophagy
      inhibition contributes to IBP-mediated tumorigenesis. In this study, we for the
      first time, reported that upregulation of IBP expression significantly suppressed
      the autophagy of breast cancer cells, and downregulation of IBP expression
      markedly induced autophagy of these cells. Further investigation revealed that
      IBP effectively counteracted autophagy by directly activating mammalian target of
      rapamycin complex 2 (mTORC2) and upregulating phosphorylation of Akt on ser473
      and FOXO3a on Thr32. Moreover, IBP-mediated suppression of autophagy was
      dependent on mTORC2/Akt/FOXO3a signaling pathway. Finally, our results
      demonstrated that IBP-mediated breast cancer cell growth in vitro and in vivo was
      strongly correlated with suppression of mTORC2-dependent autophagy. These
      findings suggest that the anti-autophagic property of IBP has an important role
      in IBP-mediated tumorigenesis, and IBP may serve as an attractive target for
      treatment of breast cancer. 

PMID- 24113177
TI  - CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of
      catecholaminergic polymorphic ventricular tachycardia.
AB  - Induced pluripotent stem cells (iPSC) offer a unique opportunity for
      developmental studies, disease modeling and regenerative medicine approaches in
      humans. The aim of our study was to create an in vitro 'patient-specific cell
      based system' that could facilitate the screening of new therapeutic molecules
      for the treatment of catecholaminergic polymorphic ventricular tachycardia
      (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of
      a cardiac model of CPVT through the generation of iPSC from a CPVT patient
      carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2)
      and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch
      clamp and intracellular electrical recordings of spontaneously beating cells
      revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in
      resting conditions and after beta-adrenergic stimulation, resembling the cardiac
      phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2
      hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N
      methylbenzylamine), an antiarrhythmic drug that inhibits Ca(2+)/calmodulin
      dependent serine-threonine protein kinase II (CaMKII), drastically reduced the
      presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by
      catecholaminergic stress. In addition, intracellular calcium transient
      measurements on 3D beating clusters by fast resolution optical mapping showed
      that CPVT clusters developed multiple calcium transients, whereas in the wild
      type clusters, only single initiations were detected. Such instability is
      aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen
      in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed
      in these human iPSC-derived cardiac cells, supporting the role of this in vitro
      system for drug screening and optimization of clinical treatment strategies. 

PMID- 24113178
TI  - Autophagy prevents irradiation injury and maintains stemness through decreasing
      ROS generation in mesenchymal stem cells.
AB  - Stem cells were characterized by their stemness: self-renewal and pluripotency.
      Mesenchymal stem cells (MSCs) are a unique type of adult stem cells that have
      been proven to be involved in tissue repair, immunoloregulation and
      tumorigenesis. Irradiation is a well-known factor that leads to functional
      obstacle in stem cells. However, the mechanism of stemness maintenance in human
      MSCs exposed to irradiation remains unknown. We demonstrated that irradiation
      could induce reactive oxygen species (ROS) accumulation that resulted in DNA
      damage and stemness injury in MSCs. Autophagy induced by starvation or rapamycin
      can reduce ROS accumulation-associated DNA damage and maintain stemness in MSCs.
      Further, inhibition of autophagy leads to augment of ROS accumulation and DNA
      damage, which results in the loss of stemness in MSCs. Our results indicate that
      autophagy may have an important role in protecting stemness of MSCs from
      irradiation injury. 

PMID- 24113179
TI  - miR-30e reciprocally regulates the differentiation of adipocytes and osteoblasts
      by directly targeting low-density lipoprotein receptor-related protein 6.
AB  - Reciprocal relationship usually exists between osteoblastogenesis and
      adipogenesis, with factors stimulating one of these processes at the same time
      inhibiting the other. In the present study, miR-30e was found to be involved in
      the reciprocal regulation of osteoblast and adipocyte differentiation. Our data
      indicated that miR-30e was induced in primarily cultured mouse bone marrow
      stromal cell, mesenchymal cell line C3H10T1/2 and preadipocyte 3T3-L1 after
      adipogenic treatment. Conversely, it was reduced in mouse stromal line ST2 and
      preosteoblast MC3T3-E1 after osteogenic treatment. Enforced expression of miR-30e
      in 3T3-L1 significantly suppressed the growth of the cells and induced the
      preadipocytes to differentiate into mature adipocytes, along with increased
      expression of adipocyte-specific transcription factors peroxisome proliferator
      activated receptor-gamma (PPARgamma), CCAAT/enhancer binding protein-alpha
      (C/EBPalpha) and C/EBPbeta, and the marker gene aP2. In contrast, inhibition of
      the endogenous miR-30e enhanced the cell growth and repressed preadipocytes to
      differentiate. Conversely, supplementing miR-30e activity blocked, whereas
      knocking down miR-30e enforced the preosteoblast MC3T3-E1 to fully differentiate.
      Furthermore, miR-30e overexpression stimulated adipocyte formation and inhibited
      osteoblast differentiation from marrow stromal cells. Low-density lipoprotein
      receptor-related protein 6 (LRP6), one of the critical coreceptor for Wnts, was
      shown to be a direct target of miR-30e by using the luciferase assay. Knockdown
      of LRP6 in 3T3-L1 cells downregulated beta-catenin/T-cell factor (TCF)
      transcriptional activity and dramatically potentiated the differentiation of the
      cells into mature adipocytes. Taken together, the present work suggests that the
      expression of miR-30e is indispensable for maintaining the balance of adipocytes
      and osteoblasts by targeting the canonical Wnt/beta-catenin signaling. 

PMID- 24113180
TI  - A novel role for the anti-senescence factor TBX2 in DNA repair and cisplatin
      resistance.
AB  - The emergence of drug resistant tumours that are able to escape cell death pose a
      major problem in the treatment of cancers. Tumours develop resistance to DNA
      damaging chemotherapeutic agents by acquiring the ability to repair their DNA.
      Combination therapies that induce DNA damage and disrupt the DNA damage repair
      process may therefore prove to be more effective against such tumours. The
      developmentally important transcription factor TBX2 has been suggested as a novel
      anticancer drug target, as it is overexpressed in several cancers and possesses
      strong anti-senescence and pro-proliferative functions. Importantly, we recently
      showed that when TBX2 is silenced, we are able to reverse several features of
      transformation in both breast cancer and melanoma cells. Overexpression of TBX2
      has also been linked to drug resistance and we have shown that its ectopic
      expression results in genetically unstable polyploidy cells with resistance to
      cisplatin. Whether the overexpression of endogenous TBX2 levels is associated
      with cisplatin resistance in TBX2-driven cancers has, however, not been shown. To
      address this we have silenced TBX2 in a cisplatin-resistant breast cancer cell
      line and we show that knocking down TBX2 sensitises the cells to cisplatin by
      disrupting the ATM-CHK2-p53 signalling pathway. Cell cycle analyses demonstrate
      that when TBX2 is knocked down there is an abrogation of an S-phase arrest but a
      robust G2/M arrest that correlates with a reduction in phosphorylated CHK2 and
      p53 levels. This prevents DNA repair resulting in TBX2-deficient cells entering
      mitosis with damaged DNA and consequently undergoing mitotic catastrophe. These
      results suggest that targeting TBX2 in combination with chemotherapeutic drugs
      such as cisplatin could improve the efficacy of current anticancer treatments. 

PMID- 24113181
TI  - The AKT1/NF-kappaB/Notch1/PTEN axis has an important role in chemoresistance of
      gastric cancer cells.
AB  - The inherent resistance of tumors to DNA damage often limits the efficacy of
      chemotherapy. The aim of this work is to explore the potential mechanism for
      development of chemoresistance in gastric cancer. Our data revealed that AKT1
      mRNA and protein expression were induced by doxorubicin (a chemotherapeutic
      agent); the doxorubicin-induced AKT1 expression and activation increased the
      binding of NF-kappaB on Notch1 DNA promoter and then promoted the Notch1
      transcription and expression; enhanced expression of Notch1 further upregulated
      PTEN expression through CBF-1 binding to PTEN DNA promoter; and inhibition of
      AKT1 expression and activity sensitized the gastric cancer cell to doxorubicin
      treatment in cultured gastric cancer cell lines and xenograft nude mice gastric
      cancer model. Furthermore, our data demonstrated that both Notch1 and PTEN were
      absent or minimally expressed in gastric cancer tissue but abundant in paired
      normal gastric mucosa, and the expression of Notch1 correlated with that of PTEN.
      Together, these novel results suggested that a novel AKT1/NF-kappaB/Notch1/PTEN
      axis has an important role in the development of chemoresistance in gastric
      cancer. Notch1 has an anti-cancer role in gastric cancer. 

PMID- 24113182
TI  - Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive
      epithelial-mesenchymal transition of cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression,
      and the TGFbeta-SMAD signaling pathway as an inductor of EMT in many tumor types
      is well recognized. However, the role of non-canonical TGFbeta-TAK1 signaling in
      EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin
      squamous cell carcinoma earlier into EMT that is conditional on the elevated
      cellular ROS level. The expression of TAK1 is consistently reduced in invasive
      squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also
      exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a
      more mesenchymal morphology characterized by higher number of focal adhesions,
      increase surface expression of integrin alpha5beta1 and active Rac1. Notably,
      these mutant cells exert an increased cell traction force, an early cellular
      response during TGFbeta1-induced EMT. The mRNA level of ZEB1 and SNAIL,
      transcription factors associated with mesenchymal phenotype is also upregulated
      in TAK1-deficient cancer cells compared with control cancer cells. We further
      show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent
      downregulation of RhoA by Rac1, which involves the oxidative modification of low
      molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1
      deficient cancer cells with Y27632, a selective inhibitor of Rho-associated
      protein kinase and antioxidant N-acetylcysteine augment and hinders EMT,
      respectively. Our findings suggest that a dysregulated balance in the activation
      of TGFbeta-TAK1 and TGFbeta-SMAD pathways is pivotal for TGFbeta1-induced EMT.
      Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced
      ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT. 

PMID- 24113183
TI  - Bringing back the help: autologous bone marrow infusion restores CD4+ T cells in
      AIDS patients with chronic liver disease.

PMID- 24113184
TI  - HIV gp120- and methamphetamine-mediated oxidative stress induces astrocyte
      apoptosis via cytochrome P450 2E1.
AB  - HIV-1 glycoprotein 120 (gp120) is known to cause neurotoxicity via several
      mechanisms including production of proinflammatory cytokines/chemokines and
      oxidative stress. Likewise, drug abuse is thought to have a direct impact on the
      pathology of HIV-associated neuroinflammation through the induction of
      proinflammatory cytokines/chemokines and oxidative stress. In the present study,
      we demonstrate that gp120 and methamphetamine (MA) causes apoptotic cell death by
      inducing oxidative stress through the cytochrome P450 (CYP) and NADPH oxidase
      (NOX) pathways. The results showed that both MA and gp120 induced reactive oxygen
      species (ROS) production in concentration- and time-dependent manners. The
      combination of gp120 and MA also induced CYP2E1 expression at both mRNA (1.7+/
      0.2- and 2.8+/-0.3-fold in SVGA and primary astrocytes, respectively) and protein
      (1.3+/-0.1-fold in SVGA and 1.4+/-0.03-fold in primary astrocytes) levels,
      suggesting the involvement of CYP2E1 in ROS production. This was further
      confirmed by using a selective inhibitor of CYP2E1, diallylsulfide (DAS), and
      CYP2E1 knockdown using siRNA, which significantly reduced ROS production (30
      60%). As the CYP pathway is known to be coupled with the NOX pathway, including
      Fenton-Weiss-Haber (FWH) reaction, we examined whether the NOX pathway is also
      involved in ROS production induced by either gp120 or MA. Our results showed that
      selective inhibitors of NOX, diphenyleneiodonium (DPI), and FWH reaction,
      deferoxamine (DFO), also significantly reduced ROS production. These findings
      were further confirmed using specific siRNAs against NOX2 and NOX4 (NADPH oxidase
      family). We then showed that gp120 and MA both induced apoptosis (caspase-3
      activity and DNA lesion using TUNEL (terminal deoxynucleotidyltransferase
      mediated dUTP nick-end labeling) assay) and cell death. Furthermore, we showed
      that DAS, DPI, and DFO completely abolished apoptosis and cell death, suggesting
      the involvement of CYP and NOX pathways in ROS-mediated apoptotic cell death. In
      conclusion, this is the first report on the involvement of CYP and NOX pathways
      in gp120/MA-induced oxidative stress and apoptotic cell death in astrocytes,
      which has clinical implications in neurodegenerative diseases, including
      neuroAIDS. 

PMID- 24113185
TI  - Translational control in the stress adaptive response of cancer cells: a novel
      role for the heat shock protein TRAP1.
AB  - TNF receptor-associated protein 1 (TRAP1), the main mitochondrial member of the
      heat shock protein (HSP) 90 family, is induced in most tumor types and is
      involved in the regulation of proteostasis in the mitochondria of tumor cells
      through the control of folding and stability of selective proteins, such as
      Cyclophilin D and Sorcin. Notably, we have recently demonstrated that TRAP1 also
      interacts with the regulatory protein particle TBP7 in the endoplasmic reticulum
      (ER), where it is involved in a further extra-mitochondrial quality control of
      nuclear-encoded mitochondrial proteins through the regulation of their
      ubiquitination/degradation. Here we show that TRAP1 is involved in the
      translational control of cancer cells through an attenuation of global protein
      synthesis, as evidenced by an inverse correlation between TRAP1 expression and
      ubiquitination/degradation of nascent stress-protective client proteins. This
      study demonstrates for the first time that TRAP1 is associated with ribosomes and
      with several translation factors in colon carcinoma cells and, remarkably, is
      found co-upregulated with some components of the translational apparatus (eIF4A,
      eIF4E, eEF1A and eEF1G) in human colorectal cancers, with potential new
      opportunities for therapeutic intervention in humans. Moreover, TRAP1 regulates
      the rate of protein synthesis through the eIF2alpha pathway either under basal
      conditions or under stress, favoring the activation of GCN2 and PERK kinases,
      with consequent phosphorylation of eIF2alpha and attenuation of cap-dependent
      translation. This enhances the synthesis of selective stress-responsive proteins,
      such as the transcription factor ATF4 and its downstream effectors BiP/Grp78, and
      the cystine antiporter system xCT, thereby providing protection against ER
      stress, oxidative damage and nutrient deprivation. Accordingly, TRAP1 silencing
      sensitizes cells to apoptosis induced by novel antitumoral drugs that inhibit cap
      dependent translation, such as ribavirin or 4EGI-1, and reduces the ability of
      cells to migrate through the pores of transwell filters. These new findings
      target the TRAP1 network in the development of novel anti-cancer strategies. 

PMID- 24113186
TI  - Multisite phosphorylation of c-Jun at threonine 91/93/95 triggers the onset of c
      Jun pro-apoptotic activity in cerebellar granule neurons.
AB  - Cerebellar granule cell (CGC) apoptosis by trophic/potassium (TK) deprivation is
      a model of election to study the interplay of pro-apoptotic and pro-survival
      signaling pathways in neuronal cell death. In this model, the c-Jun N-terminal
      kinase (JNK) induces pro-apoptotic genes through the c-Jun/activator protein 1
      (AP-1) transcription factor. On the other side, a survival pathway initiated by
      lithium leads to repression of pro-apoptotic c-Jun/AP-1 target genes without
      interfering with JNK activity. Yet, the mechanism by which lithium inhibits c-Jun
      activity remains to be elucidated. Here, we used this model system to study the
      regulation and function of site-specific c-Jun phosphorylation at the S63 and
      T91/T93 JNK sites in neuronal cell death. We found that TK-deprivation led to c
      Jun multiphosphorylation at all three JNK sites. However, immunofluorescence
      analysis of c-Jun phosphorylation at single cell level revealed that the S63 site
      was phosphorylated in all c-Jun-expressing cells, whereas the response of T91/T93
      phosphorylation was more sensitive, mirroring the switch-like apoptotic response
      of CGCs. Conversely, lithium prevented T91T93 phosphorylation and cell death
      without affecting the S63 site, suggesting that T91T93 phosphorylation triggers c
      Jun pro-apoptotic activity. Accordingly, a c-Jun mutant lacking the T95 priming
      site for T91/93 phosphorylation protected CGCs from apoptosis, whereas it was
      able to induce neurite outgrowth in PC12 cells. Vice versa, a c-Jun mutant
      bearing aspartate substitution of T95 overwhelmed lithium-mediate protection of
      CGCs from TK-deprivation, validating that inhibition of T91/T93/T95
      phosphorylation underlies the effect of lithium on cell death. Mass spectrometry
      analysis confirmed multiphosphorylation of c-Jun at T91/T93/T95 in cells.
      Moreover, JNK phosphorylated recombinant c-Jun at T91/T93 in a T95-dependent
      manner. On the basis of our results, we propose that T91/T93/T95
      multiphosphorylation of c-Jun functions as a sensitivity amplifier of the JNK
      cascade, setting the threshold for c-Jun pro-apoptotic activity in neuronal
      cells. 

PMID- 24113187
TI  - Gpr97 is essential for the follicular versus marginal zone B-lymphocyte fate
      decision.
AB  - Gpr97 is an orphan adhesion GPCR and is highly conserved among species. Up to
      now, its physiological function remains largely unknown. Here, we show that Gpr97
      deficiency results in an extensive reduction in B220(+) lymphocytes in mice. More
      intensive analyses reveal an expanded marginal zone but a decreased follicular B
      cell population in Gpr97(-/-)spleen, which displays disorganized architecture
      characterized by diffuse, irregular B-cell areas and the absence of discrete
      perifollicular marginal and mantle zones. In vivo functional studies reveal that
      the mutant mice could generate antibody responses to T cell-dependent and
      independent antigens, albeit enhanced response to the former and weakened
      response to the latter. By screening for the molecular events involved in the
      observed phenotypes, we found that lambda 5 expression is downregulated and its
      upstream inhibitor Aiolos is increased in the spleen of mutant mice, accompanied
      by significantly enhanced phosphorylation and nuclear translocation of cAMP
      response element-binding protein. Interestingly, increased constitutive Nf-kappab
      p50/p65 expression and activity were observed in Gpr97(-/-) spleen, implicating a
      crucial role of Gpr97 in regulating Nf-kappab activity. These findings uncover a
      novel biological function of Gpr97 in regulating B-cell development, implying
      Gpr97 as a potential therapeutic target for treatment of immunological disorders.

PMID- 24113188
TI  - Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and
      induced mitotic catastrophe.
AB  - Chromosomal missegregation is a common feature of many human tumors. Recent
      studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal
      segregation during mitosis; however, the molecular details have yet to be fully
      established. Observed through live cell imaging and flow cytometry, here we show
      that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest,
      metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation
      disrupted importin/karyopherin beta1 as well as the expression and localization
      of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2
      interacted with the N-terminal of importin beta1. Moreover, at least a portion of
      RanBP2 partially localizes at the centrosome during mitosis. Notably, we also
      found that GTPase Ran is also involved in the regulation of RanBP2-importin beta1
      interaction. Overall, our results suggest that mitotic arrest and the following
      cell death were caused by depletion of RanBP2. Our findings point to a crucial
      role for RanBP2 in proper mitotic progression and faithful chromosomal
      segregation. 

PMID- 24113189
TI  - Lysyl oxidase activity regulates oncogenic stress response and tumorigenesis.
AB  - Cellular senescence, a stable proliferation arrest, is induced in response to
      various stresses. Oncogenic stress-induced senescence (OIS) results in blocked
      proliferation and constitutes a fail-safe program counteracting tumorigenesis.
      The events that enable a tumor in a benign senescent state to escape from OIS and
      become malignant are largely unknown. We show that lysyl oxidase activity
      contributes to the decision to maintain senescence. Indeed, in human epithelial
      cell the constitutive expression of the LOX or LOXL2 protein favored OIS escape,
      whereas inhibition of lysyl oxidase activity was found to stabilize OIS. The
      relevance of these in vitro observations is supported by in vivo findings: in a
      transgenic mouse model of aggressive pancreatic ductal adenocarcinoma (PDAC),
      increasing lysyl oxidase activity accelerates senescence escape, whereas
      inhibition of lysyl oxidase activity was found to stabilize senescence, delay
      tumorigenesis, and increase survival. Mechanistically, we show that lysyl oxidase
      activity favors the escape of senescence by regulating the focal-adhesion kinase.
      Altogether, our results demonstrate that lysyl oxidase activity participates in
      primary tumor growth by directly impacting the senescence stability. 

PMID- 24113190
TI  - Rapid reuptake of granzyme B leads to emperitosis: an apoptotic cell-in-cell
      death of immune killer cells inside tumor cells.
AB  - A cell-in-cell process refers to the invasion of one living cell into another
      homotypic or heterotypic cell. Different from non-apoptotic death processes of
      internalized cells termed entosis or cannibalism, we previously reported an
      apoptotic cell-in-cell death occurring during heterotypic cell-in-cell formation.
      In this study, we further demonstrated that the apoptotic cell-in-cell death
      occurred only in internalized immune killer cells expressing granzyme B (GzmB).
      Vacuole wrapping around the internalized cells inside the target cells was the
      common hallmark during the early stage of all cell-in-cell processes, which
      resulted in the accumulation of reactive oxygen species and subsequent
      mitochondrial injury of encapsulated killer or non-cytotoxic immune cells.
      However, internalized killer cells mediated rapid bubbling of the vacuoles with
      the subsequent degranulation of GzmB inside the vacuole of the target cells and
      underwent the reuptake of GzmB by killer cells themselves. The confinement of
      GzmB inside the vacuole surpassed the lysosome-mediated cell death occurring in
      heterotypic or homotypic entosis processes, resulting in a GzmB-triggered caspase
      dependent apoptotic cell-in-cell death of internalized killer cells. On the
      contrary, internalized killer cells from GzmB-deficient mice underwent a typical
      non-apoptotic entotic cell-in-cell death similar to that of non-cytotoxic immune
      cells or tumor cells. Our results thus demonstrated the critical involvement of
      immune cells with cytotoxic property in apoptotic cell-in-cell death, which we
      termed as emperitosis taken from emperipolesis and apoptosis. Whereas entosis or
      cannibalism may serve as a feed-on mechanism to exacerbate and nourish tumor
      cells, emperitosis of immune killer cells inside tumor cells may serve as an in
      cell danger sensation model to prevent the killing of target cells from inside,
      implying a unique mechanism for tumor cells to escape from immune surveillance. 

PMID- 24113191
TI  - A single, multi-faceted, enhanced strategy to quantify the chromatographically
      diverse constituents in the roots of Euphorbia kansui.
AB  - Kansui radix is a famous poisonous traditional Chinese medicine. However, due to
      its different types of constituents with broad polarity, a variety of UV
      absorptions and lack of the reference standards, it was difficult to
      simultaneously determine the main component in kanui radix. A single, multi
      faceted, enhanced strategy, exogenous reference standard - single standard to
      determine multi-components method (ERS-SSDMC), was proposed. Thirteen major
      components of kansui radix, including three jatrophane diterpenoids, eight
      ingenane diterpenoids and two triterpenes, among which there were three pairs of
      isomers, were simultaneously assayed. A C8 column, packed with 2.7MUm core-shell
      particles, was optimized to separate these constituents in 25min on HPLC
      instrument detected at a program wavelength. Ethyl benzoate employed as single
      exogenous reference standard. The method was fully validated with respect to
      linearity (r(2)>0.9995), LOQs (0.1-0.4MUg/mL), precision, accuracy (92-114%,
      RSD<4.4%) and stability. The robustness of the method was performed by Plackett
      Burmantest tests which eight primary chromatographic parameters were
      investigated. It was found that the two factors, wavelength and flow rate, should
      be strictly controlled. A total of 75 batches of kansui radix and its three
      different processing products were successfully analyzed and discriminated by
      applying the proposed method. This work demonstrates an effective strategy for
      the SSDMC method making the simultaneous assay of complex multi-component TCM
      system achievable. 

PMID- 24113193
TI  - Similarities and differences in perspectives on interdisciplinary collaboration
      among hospice team members.
AB  - This study surveyed 4 core hospice professionals (physicians, nurses, social
      workers, and chaplains) on their perceived level of interdisciplinary
      collaboration, the influences of interdisciplinary collaboration, and job
      satisfaction to determine potential similarities and differences based on
      profession and various demographic characteristics of the members or member
      hospices. Analysis found that there are overall no differences based on
      demographic characteristics. Differences between professions, while few, were
      largely in the area of perceptions on relationships between members of the
      hospice team. Specifically, social workers appear to perceive themselves as less
      connected to the other members of the interdisciplinary team, an area theorized
      to influence interdisciplinary collaboration. Difference between professions was
      also found in job satisfaction. Implications for hospice practice and
      interdisciplinary education are discussed. 

PMID- 24113192
TI  - Nitric oxide-sensing H-NOX proteins govern bacterial communal behavior.
AB  - Heme-nitric oxide/oxygen binding (H-NOX) domains function as sensors for the
      gaseous signaling agent nitric oxide (NO) in eukaryotes and bacteria. Mammalian
      NO signaling is well characterized and involves the H-NOX domain of soluble
      guanylate cyclase. In bacteria, H-NOX proteins interact with bacterial signaling
      proteins in two-component signaling systems or in cyclic-di-GMP metabolism.
      Characterization of several downstream signaling processes has shown that
      bacterial H-NOX proteins share a common role in controlling important bacterial
      communal behaviors in response to NO. The H-NOX pathways regulate motility,
      biofilm formation, quorum sensing, and symbiosis. Here, we review the latest
      structural and mechanistic studies that have elucidated how H-NOX domains
      selectively bind NO and transduce ligand binding into conformational changes that
      modulate activity of signaling partners. Furthermore, we summarize the recent
      advances in understanding the physiological function and biochemical details of
      the H-NOX signaling pathways. 

PMID- 24113194
TI  - Palliative care physicians' practices and attitudes regarding advance care
      planning in palliative care units in Japan: a nationwide survey.
AB  - To clarify physicians' practices and attitudes regarding advance care planning
      (ACP) in palliative care units (PCUs) in Japan, we conducted a self-completed
      questionnaire survey of 203 certificated PCUs in 2010. Ninety-nine physicians
      participated in the survey. Although most Japanese palliative care physicians
      recognized the importance of ACP, many failed to implement aspects of patient
      directed ACP that they acknowledged to be important, such as recommending
      completion of advance directives (ADs), designation of health care proxies, and
      implementing existing ADs. The physicians' general preference for family-centered
      decision making and their feelings of difficulty and low confidence regarding ACP
      most likely underlie these results. The discrepancy between physicians' practices
      and their recognition of the importance of ACP suggests an opportunity to improve
      end-of-life care. 

PMID- 24113195
TI  - How can we improve surgical research and innovation?: the IDEAL framework for
      action.

PMID- 24113196
TI  - Gonococcemia mimicking a lupus flare in a young woman.
AB  - Gonorrhea is a common sexually transmitted infection, which can present as the
      'arthritis-dermatitis syndrome'. Patients with systemic lupus erythematosus often
      develop disseminated neisserial infections, because of inherited and acquired
      complement deficiencies. Neisserial infection, and particularly gonococcemia, can
      mimic a lupus flare. We report one case of gonococcemia presenting as acral
      papulo-vesiculous lesions of the digits in a young woman with lupus. 

PMID- 24113197
TI  - Effect of raloxifene on disease activity and vascular biomarkers in patients with
      systemic lupus erythematosus: subgroup analysis of a double-blind randomized
      controlled trial.
AB  - OBJECTIVES: The purpose of this study was to identify the effect of raloxifene on
      disease activity and vascular biomarkers in patients with systemic lupus
      erythematosus (SLE). METHODS: Subgroup data were analyzed for postmenopausal
      female SLE patients who participated in a randomized controlled trial of
      raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a
      stable daily dose of prednisolone (<=10 mg) for >=6 months were assigned to
      receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D.
      Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus
      National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians'
      global assessment (PGA) every three months. Lupus flares were assessed by the
      SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C
      reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured. RESULTS:
      A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 +/- 6.7
      years; SLE duration 9.3 +/- 7.6 years; menopause duration 7.2 +/- 6.6 years). The
      SLEDAI at entry was 1.8 +/- 2.3 (SLEDAI >= 6 in 8%). After 12 months, a
      significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p =
      0.02), and reduction in bone resorption and formation markers was observed in the
      raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA
      scores area under the curve over 12 months were not significantly different
      between the two groups. There were three episodes of mild/moderate lupus flares
      (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to
      nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological)
      in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol
      level increased significantly in the placebo but not raloxifene treated patients.
      No significant changes in homocysteine, hsCRP and sTM levels were observed in
      either group of patients. CONCLUSIONS: Raloxifene significantly improves lumbar
      spine BMD in SLE patients but does not cause an increase in lupus activity or
      flares.

PMID- 24113198
TI  - [Antiphospholipid syndrome in nephrology. Kidney damage and practical aspects of
      the management].
AB  - The antiphospholipid syndrome is a thrombophilia characterized by the combination
      of arterial and/or venous thrombotic events or obstetric clinical events,
      associated with persistent presence of antiphospholipid antibodies. In this
      syndrome, thromboses may affect all of the vascular tree, renal damage is
      frequently associated with a specific antiphospholipid syndrome nephropathy. We
      propose in this review to provide updated recommendations on the management of
      antiphospholipid syndrome in nephrology. Treatment is based on long-term
      anticoagulant therapy with or without antiplatelet agents according to clinical
      events. The use of a conventional nephroprotection must not be forgotten (strict
      control of blood pressure with drugs blocking the renin-angiotensin-aldosterone
      system). Catastrophic antiphospholipid syndrome is an extremely severe
      complication which can threaten the vital prognosis of the patient. This
      justifies particular surveillance, as well as prevention in high-risk situations.
      We also illustrate the difficulties of long-term management in these patients,
      both in dialysis or kidney transplantation. 

PMID- 24113199
TI  - [Renal replacement therapy by hemodialysis in Constantine (Algeria)].
AB  - End-stage renal failure is considered a public heath problem that constitutes a
      heavy cost on communities worldwide. To be able to plan the treatment of this
      pathology, we must have reliable and updated information through health network
      which represents the best mean for planning and reflexion locally and nationwide.
      The aim of our study was to answer to this need through a local registry of renal
      replacement therapy and nephrology network that we have for the first time an
      inventory of this pathology in an Algerian town (Constantine), and in this
      article we present the first results concerning patients under chronic
      hemodialysis. 

PMID- 24113200
TI  - [Super high-flux continuous hemodialysis in septic shock: a case report].
AB  - Continuous renal replacement therapy (CRRT) with a high cutoff (HCO) membrane is
      proposed for septic shock as a blood purification technique. The aim of this
      therapy is to modulate the immune response through the increase of the clearances
      of the inflammatory mediators as compared to standard CRRT. The use of HCO
      membranes in daily clinical practice is limited due to the related theoretical
      albumin loss. Super high-flux (SHF) membranes have an optimized cutoff and, when
      used in a diffusive mode, may allow for high clearances of middle molecules with
      limited albumin loss. We report the case of a patient with pneumonia and septic
      shock treated with continuous hemodialysis with a SHF membrane in order to
      present the clinical application of this new extracorporeal blood purification
      technique. 

PMID- 24113201
TI  - [Intravenous iron during predialysis period improves anemia management and
      cardiovascular parameters in incident hemodialysis patients].
AB  - Individualized use of iron therapy (IT) and erythropoiesis-stimulating agents
      (ESA) may effectively correct anemia and its symptoms in CKD patients (Pts). The
      aim of this retrospective study was to precise the anemia management (AM) in
      incident HD Pts, and to compare Pts treated by intravenous (i.v.) IT and ESA
      during predialysis to those treated by oral IT and ESA on AM and cardiovascular
      parameters during the first year of HD. One hundred and two Pts performed their
      first dialysis in the unit, mean age 58.5 (15.9) years, 70% males, 27% diabetes.
      Ninety Pts started with a native arteriovenous fistula. Charlson comorbidity
      index was 7.3 (3.5). Mortality rate was 3% at one year. Hb level was at start
      10.6 (1.7) and at one year 11.7 (1.1) g/dL (P<0.0001). DA injected every 2weeks
      was at the beginning at 107 (56) MUg and then at 61 (46) (P<0.0001). i.v. IT
      injected every week was at the dosage of 87 (23) mg and then at 57 (40mg) per
      injection (P<0.001). Out of 102 Pts, 33 received i.v. IT during predialysis.
      These Pts started dialysis with a better Hb level: 11.1 (1.3) versus 10.4 (1.55)
      g/dL (P<0.01), had a TSAT at 50.0 (19.2) versus 30.1 (15.2) % (P<0.001), received
      less ESA 0.58 (0.28) versus 0.82 (0.37) MUg/kg per week (P<0.01). More important
      were the changes on the cardiovascular functions: left ventricular mass at 116
      (34) versus 134 (39) g/m(2) (P<0.02), left ventricular ejection fraction at 64.7
      (4.4) versus 61.4 (8.7) % (P<0.02) and mean arterial pressure at 104.7 (80)
      versus 109 (13.2) mmHg (P<0.02). These Pts were also less hospitalized. This
      study revealed the importance of i.v. IT during predialysis care not only on AM
      but also on cardiovascular status in HD Pts starting dialysis. 

PMID- 24113202
TI  - [Spectrum of renal manifestations in sickle cell disease].
AB  - Sickle cell disease (SCD), the most common hemoglobinopathy, is an increasing
      cause of chronic kidney disease. In the last decade, we have witnessed a better
      understanding in the characterization of clinical manifestations and pathogenesis
      of sickle cell nephropathy. The spectrum of renal diseases during SCD includes
      various renal manifestations such as impairment of urinary concentrating ability,
      defect in urine acidification, renal papillary necrosis and proteinuria related
      to glomerular injury leading to progressive end-stage renal disease. Endothelial
      dysfunction related to chronic hemolysis and the relative renal hypoxia caused by
      vaso-occlusive sickle red blood cells are probably two key factors for SCN
      development. Optimal therapeutic management (including the use of blockers of the
      renin-angiotensin system) of patients with proteinuria remains to be determined.
      Renal replacement therapy with dialysis is required in SCD patients with end
      stage renal disease but these patients should probably undergo kidney
      transplantation that requires careful management.

PMID- 24113203
TI  - [The histone mark in acute renal failure].

PMID- 24113204
TI  - Is rapid hepatitis C virus testing from corpses a screening option for index
      persons who have died after mass-casualty incidents in high-prevalence settings
      in the field?
AB  - INTRODUCTION: We tested a commercially available rapid hepatitis C virus (HCV)
      test assay for its potential use for analyses of corpses as a screening option
      for index persons who have died after mass-casualty incidents in high-prevalence
      settings in the field. MATERIALS AND METHODS: 50 blood samples were drawn from 16
      recently deceased confirmed HCV-positive patients whose corpses were stored at 4
      degrees C in the mortuary and were analysed at admission and up to 48 h post
      mortem by rapid serological testing using the ImmunoFlow HCV test (Core
      Diagnostics, Birmingham, UK) in comparison with automated serological assays and
      PCR. Samples from 50 HCV-negative corpses were also analysed. RESULTS: The blood
      of only four of the 16 HCV-positive corpses reacted clearly with the ImmunoFlow
      HCV test, while in five cases the result was only weakly reactive and three cases
      showed very weak reactivity. Four of the infected corpses showed initially
      negative results, three of which became very weakly reactive 48 h post mortem. 49
      out of 50 samples (98%) from HCV-negative corpses tested negative. DISCUSSION:
      The rapid test system we investigated showed insufficient sensitivity regarding
      the identification of HCV positivity. Automated serological testing or PCR should
      be preferred if it is realistically available in the deployed military setting.

PMID- 24113205
TI  - A model of memory impairment in schizophrenia: cognitive and clinical factors
      associated with memory efficiency and memory errors.
AB  - BACKGROUND: Memory impairments in patients with schizophrenia have been
      associated with various cognitive and clinical factors. Hallucinations have been
      more specifically associated with errors stemming from source monitoring failure.
      METHODS: We conducted a broad investigation of verbal memory and visual memory as
      well as source memory functioning in a sample of patients with schizophrenia.
      Various memory measures were tallied, and we studied their associations with
      processing speed, working memory span, and positive, negative, and depressive
      symptoms. RESULTS: Superficial and deep memory processes were differentially
      associated with processing speed, working memory span, avolition, depression, and
      attention disorders. Auditory/verbal and visual hallucinations were
      differentially associated with specific types of source memory error.
      CONCLUSIONS: We integrated all the results into a revised version of a previously
      published model of memory functioning in schizophrenia. The model describes the
      factors that affect memory efficiency, as well as the cognitive underpinnings of
      hallucinations within the source monitoring framework.

PMID- 24113206
TI  - Effects of maternal immune activation on adult neurogenesis in the subventricular
      zone-olfactory bulb pathway and olfactory discrimination.
AB  - Maternal infection and maternal immune activation (MIA) during pregnancy increase
      risks for psychiatric disorders such as schizophrenia and autism. Many deficits
      related to psychiatric disorders are observed in adult offspring of MIA animal
      models, including behavioral abnormalities, morphological defects in various
      brain regions, and dysregulation of neurotransmitter systems. It has previously
      been shown that MIA impairs adult neurogenesis in the dentate gyrus of the
      hippocampus. In this study, we examined whether MIA affects adult neurogenesis in
      the subventricular zone (SVZ)-olfactory bulb (OB) pathway. Polyinosinic
      polycytidylic acid (PolyI:C), a synthetic analog of double-stranded RNA mimicking
      viral infection, was injected into pregnant mice on gestation day 9.5 to activate
      immune systems. In the SVZ-OB pathway of adult offspring, different cell types of
      the neural stem cell lineage responded differently to MIA. Neural stem cells and
      neuroblasts were decreased. Cell proliferation of transit-amplifying cells was
      impaired. Consequently, newborn neurons were reduced in the OB. Olfactory
      deficiency has been suggested as a biomarker for schizophrenia. Here we found
      that olfactory discrimination was compromised in adult MIA offspring. Taken
      together, these findings show that MIA leads to defective adult neurogenesis in
      the SVZ-OB pathway, and the impairment of adult neurogenesis may lead to deficits
      in olfactory functions.

PMID- 24113207
TI  - Silicon species in seawater.

PMID- 24113209
TI  - A Mobius strip of scientific imagination. How deep does the relationship between
      science fiction and science go?

PMID- 24113210
TI  - StaR Child Health: improving global standards for child health research.
AB  - Standards for Research (StaR) in Child Health, founded in 2009, addresses the
      current scarcity of and deficiencies in pediatric clinical trials. StaR Child
      Health brings together leading international experts devoted to developing
      practical, evidence-based standards to enrich the reliability and relevance of
      pediatric clinical research. Through a systematic "knowledge to action" plan,
      StaR Child Health creates opportunities to improve the evidence base for child
      health across the world. To date, six standards have been published and four more
      are under development. It is now time to use these standards. Improving the
      design, conduct and reporting of pediatric clinical trials will ultimately
      advance the quality of health care provided to children across the globe. 

PMID- 24113208
TI  - No need for a power stroke in ISWI-mediated nucleosome sliding.
AB  - Nucleosome remodelling enzymes of the ISWI family reposition nucleosomes in
      eukaryotes. ISWI contains an ATPase and a HAND-SANT-SLIDE (HSS) domain.
      Conformational changes between these domains have been proposed to be critical
      for nucleosome repositioning by pulling flanking DNA into the nucleosome. We
      inserted flexible linkers at strategic sites in ISWI to disrupt this putative
      power stroke and assess its functional importance by quantitative biochemical
      assays. Notably, the flexible linkers did not disrupt catalysis. Instead of
      engaging in a power stroke, the HSS module might therefore assist DNA to ratchet
      into the nucleosome. Our results clarify the roles had by the domains and suggest
      that the HSS domain evolved to optimize a rudimentary remodelling engine. 

PMID- 24113211
TI  - Weight corrected percentiles for blood vessel diameters used in flow measurements
      in preterm infants.
AB  - BACKGROUND: Blood flow measurements are an integral part of haemodynamic
      assessment of the newborn infant. Most variability of Doppler derived blood flow
      is caused by diameter measurements. Population based percentiles of diameter
      measurements would be useful for training of clinicians undertaking blood flow
      measurements and allow rapid identification of outliers. METHODS: Diameter
      measurements of pulmonary valve annulus, ascending aorta and the superior vena
      cava using standardised methodology were collected retrospectively from 9
      prospective studies on transitional haemodynamics in preterm infants. Data were
      analysed to calculate weight corrected percentiles of diameters used for blood
      flow measurements. RESULTS: We analysed 2870 measurements in 694 preterm infants
      less than 1750 g. The median gestational age was 27 weeks (range 23 to 34 weeks)
      and the median time of measurement was 22 h after birth (range 0.5 h to 70 days).
      76% of measurements were performed while the infant received mechanical
      ventilation and 20% received cardiovascular support. Mean diameters increased
      with weight and standard deviations were comparable over the weight range.
      CONCLUSION: Data from this large combined series provide a reference range for
      blood vessel diameters in the population most often measured. The data permits
      recognition of outliers and could be used to trigger review of measurements that
      fall outside the normal range.

PMID- 24113212
TI  - Neonatal and longer term management following substance misuse in pregnancy.
AB  - Substance misuse in pregnancy is not a new problem, but although impaired foetal
      growth and the risk of developing neonatal abstinence syndrome are widely
      appreciated, relatively little attention has been paid to longer term
      consequences for the infant. Available evidence indicates that prenatal exposure
      to opioids and other drugs of misuse is detrimental to the developing foetal
      brain; consistent with this, poor in utero head growth, delayed infant visual
      maturation and impaired general neurodevelopmental progress independent of social
      confounders are increasingly being recognised. This review considers current
      evidence and discusses best practice in the neonatal management and follow-up of
      affected babies. More studies are required to explore alternatives to methadone
      maintenance in pregnancy and to define optimal treatment for neonatal abstinence
      syndrome. All infants born to drug-misusing mothers must be considered
      vulnerable, even if they have not required treatment for neonatal abstinence
      syndrome. 

PMID- 24113213
TI  - A comprehensive review of microbial electrochemical systems as a platform
      technology.
AB  - Microbial electrochemical systems (MESs) use microorganisms to covert the
      chemical energy stored in biodegradable materials to direct electric current and
      chemicals. Compared to traditional treatment-focused, energy-intensive
      environmental technologies, this emerging technology offers a new and
      transformative solution for integrated waste treatment and energy and resource
      recovery, because it offers a flexible platform for both oxidation and reduction
      reaction oriented processes. All MESs share one common principle in the anode
      chamber, in which biodegradable substrates, such as waste materials, are oxidized
      and generate electrical current. In contrast, a great variety of applications
      have been developed by utilizing this in situ current, such as direct power
      generation (microbial fuel cells, MFCs), chemical production (microbial
      electrolysis cells, MECs; microbial electrosynthesis, MES), or water desalination
      (microbial desalination cells, MDCs). Different from previous reviews that either
      focus on one function or a specific application aspect, this article provides a
      comprehensive and quantitative review of all the different functions or system
      constructions with different acronyms developed so far from the MES platform and
      summarizes nearly 50 corresponding systems to date. It also provides discussions
      on the future development of this promising yet early-stage technology. 

PMID- 24113215
TI  - Sex differences in the effect of cytochrome P450 2C19 polymorphisms on the risk
      of diabetic retinopathy: a retrospective longitudinal study in Japanese patients
      with type 2 diabetes.
AB  - Cytochrome P450 2C19 (CYP2C19) is expressed in human endothelial cells and
      catalyzes the biosynthesis of vasoprotective epoxyeicosatrienoic acids and 19
      hydroxyeicosatetraenoic acid from arachidonic acid. This study investigated the
      association between CYP2C19 polymorphisms and an increased risk of diabetic
      retinopathy (DR). A clinic-based retrospective longitudinal analysis was carried
      out that included 383 Japanese patients with type 2 diabetes mellitus. Compared
      with male extensive metabolizers, female intermediate metabolizers [adjusted odds
      ratio (OR), 2.43; 95% confidence interval (95% CI), 1.17-5.06] and poor
      metabolizers (OR, 7.49; 95% CI, 2.64-21.26) were at a significantly higher risk
      of developing DR. Furthermore, the CYP2C19 poor metabolizer genotype was found to
      be an independent risk factor for DR only in women when patients were stratified
      by sex (OR, 4.18; 95% CI, 1.42-12.26). This is the first report showing the
      interactive effect of sex and CYP2C19 polymorphisms on microvascular disease in
      humans, although further investigations are needed to verify these findings. 

PMID- 24113216
TI  - Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome
      proliferator-activated receptor-alpha are associated with the development of new
      onset diabetes after transplantation in kidney transplant recipients treated with
      tacrolimus.
AB  - BACKGROUND: New-onset diabetes after transplantation (NODAT) is an important
      complication after kidney transplantation. The etiology of the malady is
      multifactorial and includes both environmental and genetic factors. NODAT is a
      polygenic disease and many single-nucleotide polymorphisms could constitute
      potential risk factors. Peroxisome proliferator-activated receptor alpha
      (PPARalpha) and P450 oxidoreductase (POR) play a central role in the control of
      energy metabolism in humans. Some recent data highlighted a possible functional
      impact of two single-nucleotide polymorphisms in PPARalpha (rs4253728 G>A and
      rs4823613 A>G) and one coding variant in POR (rs1057868; POR*28; A503V) on the
      activity of their respective encoded proteins. In the present study, we assessed
      the association between these variants and the risk of developing NODAT after
      kidney transplantation. METHODS: Development of NODAT was investigated in 101
      renal transplant recipients receiving tacrolimus-based immunosuppressive therapy.
      Patients were genotyped for PPARalpha and POR. The incidence of NODAT was
      compared between different genotypes. Kaplan-Meier and Cox's proportional-hazard
      analysis were used to evaluate the association of NODAT with potential risk
      factors. Potential nongenetic risk factors were also considered. RESULTS: The
      PPARalpha rs4253728A>G and POR*28 variant alleles were both independently
      associated with an increased risk for NODAT with respective odds ratios of 8.6
      [95% confidence interval (CI)=1.4-54.2; P=0.02] and 8.1 (95% CI=1.1-58.3;
      P=0.04). Other risk predictors included sex and body weight. CONCLUSION: This
      candidate-gene study shows that polymorphisms in PPARalpha and POR might
      predispose patients being treated with tacrolimus to the development of NODAT
      after kidney transplantation. Patient management after organ transplantation
      might benefit from genotype data.

PMID- 24113214
TI  - Nanoparticles containing insoluble drug for cancer therapy.
AB  - Nanoparticle drug formulations have been extensively researched and developed in
      the field of drug delivery as a means to efficiently deliver insoluble drugs to
      tumor cells. By mechanisms of the enhanced permeability and retention effect,
      nanoparticle drug formulations are capable of greatly enhancing the safety,
      pharmacokinetic profiles and bioavailability of the administered treatment. Here,
      the progress of various nanoparticle formulations in both research and clinical
      applications is detailed with a focus on the development of drug/gene delivery
      systems. Specifically, the unique advantages and disadvantages of polymeric
      nanoparticles, liposomes, solid lipid nanoparticles, nanocrystals and lipid
      coated nanoparticles for targeted drug delivery will be investigated in detail. 

PMID- 24113217
TI  - Enhanced adaptive management: integrating decision analysis, scenario analysis
      and environmental modeling for the Everglades.
AB  - We propose to enhance existing adaptive management efforts with a decision
      analytical approach that can guide the initial selection of robust restoration
      alternative plans and inform the need to adjust these alternatives in the course
      of action based on continuously acquired monitoring information and changing
      stakeholder values. We demonstrate an application of enhanced adaptive management
      for a wetland restoration case study inspired by the Florida Everglades
      restoration effort. We find that alternatives designed to reconstruct the pre
      drainage flow may have a positive ecological impact, but may also have high
      operational costs and only marginally contribute to meeting other objectives such
      as reduction of flooding. Enhanced adaptive management allows managers to guide
      investment in ecosystem modeling and monitoring efforts through scenario and
      value of information analyses to support optimal restoration strategies in the
      face of uncertain and changing information. 

PMID- 24113218
TI  - A novel chemodosimeter for fluoride ions based on deprotonation of the C-H group
      followed by an autoxidative decyanation process.
AB  - A novel chemodosimeter for fluoride ions (F(-)) based on deprotonation of the C-H
      group followed by an autoxidative decyanation process has been developed for the
      first time, with a "naked-eye" response (OFF-ON-OFF) and ratiometric
      chromofluorogenic selective sensing for F(-). 

PMID- 24113219
TI  - Heat dissipation from suspended self-heated nanowires: gas sensor prospective.
AB  - The strong temperature dependence of the electrical conductivity in
      semiconductors was employed for gas and pressure sensing with a self-heated Si
      nanowire resistor. The electrical conductivity in such a device depends on heat
      dissipation and partitioning inside the device and was studied comparatively for
      suspended and supported device architectures. The appearance of the exhaustion
      region in the temperature-dependent resistivity of a Joule-heated nanowire was
      used as a temperature marker for implementation of the quasi-constant temperature
      operation mode. At low pressures, the sensor is idle due to dominant heat
      dissipation from the nanowire to the substrate and/or electrodes. Above ca. 10
      Torr the sensitivity to gases has a strong dependence on pressure as well as on
      the type of gas and is determined by conductive heat transfer between the
      nanowire surface and ambient. This implies that, in contrast to macroscopic
      devices, the heat dissipation via the convection mechanism does not contribute
      significantly to the heat transfer from the self-heated nanowire. The thermal
      sensitivity of the sensor to reactive gases depends on the effectiveness of the
      particular endothermic/exothermic reaction at the surface of the nanowire and was
      explored for the case of acetone-air mixture. The strong coupling of the
      electrical and thermal properties in the individual Joule-heated semiconducting
      nanowire allows fabrication of power-efficient multi-parametric nanoscopic
      gas/pressure sensors that are analogs of Pirani and pellistor type detectors.

PMID- 24113221
TI  - Characterization of swarming and mating behaviour between Anopheles coluzzii and
      Anopheles melas in a sympatry area of Benin.
AB  - The swarm structure of two sibling species, Anopheles gambiae coluzzii and
      Anopheles melas, was characterize to explore the ecological and environmental
      parameters associated with the formation of swarms and their spatial
      distribution. Swarms and breeding sites were searched and sampled between January
      and December 2010, and larval and adult samples were identified by PCR. During
      the dry season, 456 swarms of An. gambiae s.l. were sampled from 38 swarm sites
      yielding a total of 23,274 males and 76 females. Of these 38 swarming sites, 18
      were composed exclusively of An. gambiae coluzzii and 20 exclusively of An.
      melas, presenting clear evidence of reproductive swarm segregation. The species
      makeup of couples sampled from swarms also demonstrated assortative mating. The
      swarm site localization was close to human dwellings in the case of the An.
      gambiae coluzzii and on salt production sites for An. melas. At the peak of the
      rainy season, swarms of An. melas were absent. These findings offer evidence that
      the ecological speciation of these two sibling species of mosquitoes is
      associated with spatial swarm segregation and assortative mating, providing
      strong support for the hypothesis that mate recognition is currently maintaining
      adaptive differentiation and promoting ecological speciation. Further studies on
      the swarming and mating systems of An. gambiae, with the prospect of producing a
      predictive model of swarm distribution, are needed to inform any future efforts
      to implement strategies based on the use of GMM or SIT. 

PMID- 24113220
TI  - Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency:
      role of LDL receptor upregulation.
AB  - Adiponectin is an adipokine that can suppress the proliferation of various human
      carcinoma cells. Although its anti-tumor activities have been suggested by many
      clinical investigations and animal studies, the underlying mechanisms are not
      fully characterized. In MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic
      mice models, reduced- or complete loss-of-adiponectin expression promotes mammary
      tumor development. The present study demonstrated that while tumor development in
      control MMTV-PyVT mice is associated with a progressively decreased circulating
      cholesterol concentration, adiponectin deficient MMTV-PyVT mice showed
      significantly elevated total- and low density lipoprotein (LDL)-cholesterol
      levels. Cholesterol contents in tumors derived from adiponectin deficient mice
      were dramatically augmented. High fat high cholesterol diet further accelerated
      the tumor development in adiponectin deficient PyVT mice. The protein levels of
      LDL receptor (LDLR) were found to be upregulated in adiponectin-deficient tumor
      cells. In human breast carcinoma cells, treatment with LDL-cholesterol or
      overexpressing LDLR elevates nuclear beta-catenin activity and facilitates tumor
      cell proliferation. On the other hand, adiponectin decreased LDLR protein
      expression in breast cancer cells and inhibited LDL-cholesterol-induced tumor
      cell proliferation. Both in vivo and in vitro evidence demonstrated a stimulatory
      effect of adiponectin on autophagy process, which mediated the down-regulation of
      LDLR. Adiponectin-induced reduction of LDLR was blocked by treatment with a
      specific inhibitor of autophagy, 3-methyladenine. In conclusion, the study
      demonstrates that adiponectin elicits tumor suppressive effects by modulating
      cholesterol homeostasis and LDLR expression in breast cancer cells, which is at
      least in part attributed to its role in promoting autophagic flux. 

PMID- 24113222
TI  - Advancing avian behavioral neuroendocrinology through genomics.
AB  - Genome technologies are transforming all areas of biology, including the study of
      hormones, brain and behavior. Annotated reference genome assemblies are rapidly
      being produced for many avian species. Here we briefly review the basic concepts
      and tools used in genomics. We then consider how these are informing the study of
      avian behavioral neuroendocrinology, focusing in particular on lessons from the
      study of songbirds. We discuss the impact of having a complete "parts list" for
      an organism; the transformational potential of studying large sets of genes at
      once instead one gene at a time; the growing recognition that environmental and
      behavioral signals trigger massive shifts in gene expression in the brain; and
      the prospects for using comparative genomics to uncover the genetic roots of
      behavioral variation. Throughout, we identify promising new directions for
      bolstering the application of genomic information to further advance the study of
      avian brain and behavior. 

PMID- 24113223
TI  - The assessment of the quality of life of adults with intellectual disability: the
      use of self-report and report of others assessment strategies.
AB  - Assessment strategies that reliably and validly assess the indicators of quality
      of life (QOL) of individuals with intellectual disability (ID) are necessary for
      planning interventions and evaluating outcomes. In the present study, inter-rater
      reliability and concordance of the two assessment strategies report of others and
      self-report were evaluated in a group of 176 Italian adults with ID using the
      Personal Outcomes Scale, which employs the same QOL indicators in the self-report
      and report of others versions. Report of others resulted a reliable assessment
      strategy. Clients' point of view was compared with both the estimation of their
      point of view and third-party-point-of-view obtained by two independent
      caregivers for each client. Results indicated that both self-report and report of
      others assessment strategies are necessary and that estimation of the client's
      point of view may be a valid and reliable substitute of self-report when clients
      are not able to answer. 

PMID- 24113224
TI  - Transcriptional regulation of secondary metabolite biosynthesis in plants.
AB  - Plants produce thousands of secondary metabolites (a.k.a. specialized
      metabolites) of diverse chemical nature. These compounds play important roles in
      protecting plants under adverse conditions. Many secondary metabolites are valued
      for their pharmaceutical properties. Because of their beneficial effects to
      health, biosynthesis of secondary metabolites has been a prime focus of research.
      Many transcription factors have been characterized for their roles in regulating
      biosynthetic pathways at the transcriptional level. The emerging picture of
      transcriptional regulation of secondary metabolite biosynthesis suggests that the
      expression of activators and repressors, in response to phytohormones and
      different environmental signals, forms a dynamic regulatory network that fine
      tune the timing, amplitude and tissue specific expression of pathway genes and
      the subsequent accumulation of these compounds. Recent research has revealed that
      some metabolic pathways are also controlled by posttranscriptional and
      posttranslational mechanisms. This review will use recent developments in the
      biosynthesis of flavonoids, alkaloids and terpenoids to highlight the complexity
      of transcriptional regulation of secondary metabolite biosynthesis. 

PMID- 24113225
TI  - Characteristics and outcome of liver transplantation in children with Alagille
      syndrome: a single-center experience.
AB  - BACKGROUND: This study was carried out in Chang Gung Memorial Hospital-Kaohsiung
      Medical Center, Taiwan, with the aim of reviewing the characteristics and the
      outcome of liver transplantation (LT) in children with Alagille syndrome (AGS).
      METHODS: We performed a retrospective analysis of transplant records of children
      diagnosed with AGS and undergoing LT between 1987 and 2010. RESULTS: Nine
      patients underwent living donor LT. Cholestasis and characteristic facies were
      seen in all patients. Posterior embryotoxon was seen in 4/9 (44.4%), butterfly
      vertebrae in 3/9 (33.3%), heart defect (pulmonary stenosis in 2) in 3/9 (33.3%),
      and renal disease in 2/9 (22.2%) patients. Five cases had cholestasis prior to
      the age of 60 days, whereas four cases had cholestasis after 60 days of age.
      Iminodiacetic acid scans showed no excretion of isotope into the bowel in four
      cases and suggested a false diagnosis of biliary atresia. All patients underwent
      diagnostic laparotomy and liver biopsy. Results of liver biopsy showed
      characteristic features of paucity of interlobular bile ducts in all patients.
      Kasai portoenterostomy was not performed in any patient prior to being referred
      for LT. The mean age at the time of LT was 4.6 years. The 5-year overall survival
      rate after living donor LT was 88.9%. CONCLUSION: Our conclusion is that the
      clinical features of AGS are informative. In addition, histological confirmation
      is important in the diagnosis. AGS children with severe liver disease had good
      prognoses with LT.

PMID- 24113226
TI  - Candidemia and death by Candida orthopsilosis and Candida metapsilosis in
      neonates and children.

PMID- 24113227
TI  - Influenza B virus-associated pneumonia in pediatric patients: clinical features,
      laboratory data, and chest X-ray findings.
AB  - BACKGROUND: The clinical significance of influenza B is frequently overlooked,
      and reports on influenza B pneumonia in children are limited. Therefore, the
      clinical features of associated complications have rarely been reported. The aim
      of this study is to evaluate the clinical characteristics in pediatric patients
      with influenza B virus-associated pneumonia. METHODS: From January 2009 to
      February 2012, 389 consecutive patients under 18 years old with influenza B virus
      infection were enrolled into the study. Thirty-four patients were defined as the
      pneumonia group by clinical symptoms and chest X-ray (CXR) findings, and 90
      patients who had laboratory data and normal CXR findings were recruited to form
      the nonpneumonia group. RESULTS: The age of the patients in the pneumonia group
      was significantly younger (median of 5.3 vs. 6.6 years). The white blood cell
      count (median of 7.5 vs. 5.7 * 10(9) cells/L) and C-reactive protein level
      (median of 21.1 vs. 5.7 mg/L) were higher, but the hemoglobin level was lower
      (median of 12.6 vs. 13.2 g/dL) in the pneumonia group. The CXR findings revealed
      that 29.4% of patients had alveolar consolidation, 32.4% had interstitial
      infiltration, and 38.2% had ground glass opacity. Two of four patients with
      pleural effusion had a positive bacteria culture, and both of them died.
      CONCLUSION: Pneumonia should be considered in pediatric patients with influenza B
      virus infection presenting with younger age, higher white blood cell count, lower
      hemoglobin, and higher C-reactive protein level. The CXR findings were varied.
      Patients with pleural effusion and positive bacterial culture may have more
      severity of clinical outcome.

PMID- 24113228
TI  - X-linked lymphoproliferative syndromes and related autosomal recessive disorders.
AB  - PURPOSE OF REVIEW: X-linked lymphoproliferative (XLP) syndromes and related
      autosomal disorders are severe primary immune deficiencies triggered by infection
      with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis.
      Recent findings reviewed herein provided key new insights into the genetic and
      immunological basis of these diseases. They also improved our comprehension of
      the immunological mechanisms controlling EBV infection. RECENT FINDINGS:
      Mutations of an X-linked gene, SH2D1A, which encodes the signaling lymphocytic
      activation molecule (SLAM)-associated protein (SAP), are responsible for most
      cases of XLP disorders. More recently, other genetic causes for XLP syndromes and
      autosomal recessive variants of this disease were elucidated. Mutations in genes
      such as XIAP, ITK, and CD27 were identified. The clinical manifestations and
      immunological defects seen in these patients were characterized. SUMMARY: The
      similarities and differences in immunological defects and clinical manifestations
      between XLP syndromes and related autosomal recessive disorders enabled important
      new insights into the pathogenesis of these diseases. They also helped our
      comprehension of the mechanisms implicated in the control of EBV infection. They
      suggested that CD8+ T cells, natural killer (NK) cells, and NKT cells are
      critically involved.

PMID- 24113229
TI  - Recent advances in understanding and managing adenosine deaminase and purine
      nucleoside phosphorylase deficiencies.
AB  - PURPOSE OF THE REVIEW: To review the recent advances in the understanding and
      management of the immune and nonimmune effects of inherited adenosine deaminase
      (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. RECENT FINDINGS:
      Abnormal thymocyte development and peripheral T-cell activation in ADA-deficient
      and PNP-deficient patients cause increased susceptibility to infections and
      immune dysregulation. The impaired purine homeostasis also damages many other
      cell types and tissues. Animal studies suggest that defects in surfactant
      metabolism by alveolar macrophages cause the pulmonary alveolar proteinosis
      commonly seen in ADA-deficient infants, while toxicity of purine metabolites to
      cerebellar Purkinje cells may lead to the ataxia frequently observed in PNP
      deficiency. Patients' outcome with current treatments including enzyme
      replacement and stem cell transplantations are inferior to those achieved in most
      severe immunodeficiency conditions. New strategies, including intracellular
      enzyme replacement, gene therapy and innovative protocols for stem cell
      transplantations hold great promise for improved outcomes in ADA and PNP
      deficiency. Moreover, newborn screening and early diagnosis will allow prompt
      application of these novel treatment strategies, further improving survival and
      reducing morbidity. SUMMARY: Better understanding of the complex immune and
      nonimmune effects of ADA and PNP deficiency holds great promise for improved
      patients' outcome.

PMID- 24113230
TI  - Plastics bags reduce hypothermia in newly born infants in the developing world.

PMID- 24113231
TI  - Modest weight loss does not decrease cardiovascular morbidity and mortality in
      adults with type 2 diabetes.

PMID- 24113232
TI  - Ibuprofen does not seem to increase global malformation risk but NSAID use in
      late pregnancy remains a concern.

PMID- 24113233
TI  - Cardiovascular benefits of HRT may differ by patient age.

PMID- 24113234
TI  - High-performance liquid chromatographic method for the determination of dasatinib
      in rabbit plasma using fluorescence detection and its application to a
      pharmacokinetic study.
AB  - A highly selective, sensitive, and rapid high performance liquid chromatographic
      (HPLC) method has been developed and validated to quantify dasatinib, a tyrosine
      kinase inhibitor, in rabbit plasma. Montelukast was used as internal standard
      (IS). Dasatinib and IS were extracted by deproteinization technique, followed by
      injection of aliquot of supernatant into chromatographic system. Chromatographic
      separation was achieved on a reversed phase C18 column with a mobile phase of
      0.02M potassium dihydrogen phosphate:methanol (10:90, v/v) pumped at flow rate of
      2.0mL/min. The analytes were detected at 340 and 374nm for excitation and
      emission, respectively. The assay exhibited a linear range of 50.0-3000ng/mL,
      with a lower detection limit of 15.0ng/mL. The method was statistically validated
      for linearity, accuracy, precision, selectivity and stability following FDA
      guidelines. The intra- and inter-assay coefficients of variation did not exceed
      13.5% from the nominal concentration. The accuracy of dasatinib was within +/-15%
      of the theoretical value. The assay has been applied successfully in a
      pharmacokinetic study. 

PMID- 24113235
TI  - Comparison of three methods for measuring thiopurine methyltransferase activity
      in red blood cells and human leukemia cells.
AB  - Thiopurine efficacy is partly reflected by the genetic polymorphism of the
      thiopurine methyltransferase (TPMT) enzyme, which is responsible for variation in
      the metabolism, toxicity and therapeutic efficacy of the thiopurines azathioprine
      (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). Determination of TPMT
      activity before administration of thiopurines is thus crucial for individualized
      dosing in order to prevent toxicity in TPMT deficient individuals. These
      individuals must be treated with markedly lower (eg, 5-10% of the standard) doses
      of the prescribed medications. This paper describes a comparison of three
      different methods for the quantification of TPMT activity in red blood cells
      (RBC) and cultured human cell lines. We succeeded to perform the measurement of
      TPMT activity in a minimum amount of 1*10(6) cultured cells with an HPLC-UV
      system modified and optimized in our laboratory. The TPMT activity was linearly
      correlated with the cell concentration of the cultured cell line in a range of 1
      10*10(6) cells. A significant correlation of determination of TPMT activity in
      RBC between radiometric detection by HPLC, classic radiochemical detection and UV
      detection by HPLC, was observed, correlation coefficient (r) were 0.72 and 0.73,
      respectively. The within-day and day-to-day coefficients of variation of the HPLC
      UV-based method were 8% and 16%, respectively. The evaluation of the methods was
      demonstrated by studying the TPMT activity in RBC isolated from 198 patients, as
      well as in MOLT4 leukemic cell line and its sub-cell lines with acquired
      resistance to 6-MP and 6-TG. 

PMID- 24113236
TI  - Quantitative determination of arenobufagin in rat plasma by ultra fast liquid
      chromatography-tandem mass spectrometry and its application in a pharmacokinetic
      study.
AB  - A rapid, sensitive, and selective ultra fast liquid chromatography-tandem mass
      spectrometry method was developed for quantitative determination of arenobufagin
      in rat plasma. Sample pretreatment involved a one-step protein precipitation with
      methanol using 0.1mL rat plasma. The separation was carried out on a Shim-pack XR
      ODS II (75mm*2.0mm, i.d. 2.1MUm) column with gradient elution at a flow rate of
      0.30mLmin(-1). The mobile phase was acetonitrile and 0.1% formic acid in water. A
      post-column switching valve was applied to reduce the matrix effect. The
      detection was performed on a triple-quadruple tandem mass spectrometer in the
      multiple reaction monitoring mode after electrospray ionization. Linear
      calibration curves for arenobufagin were obtained over the concentration range
      1.056-1056ngmL(-1), with a lower limit of quantification of 1.056ngmL(-1). The
      intra-day and inter-day precision values were lower than 15% and the accuracy
      ranged from 5.4% to 9.8% at all quality control levels. The method was
      successfully applied to the determination and pharmacokinetic study of
      arenobufagin in rat plasma following intraperitoneal administration. 

PMID- 24113237
TI  - Simultaneous quantification of mycotoxins and pesticide residues in ginseng with
      one-step extraction using ultra-high performance liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - This study describes the development and validation of a simple, accurate and
      sensitive ultra high-performance liquid chromatography-electrospray ionization
      tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the simultaneous
      quantification of 10 mycotoxins and 29 pesticides in ginseng. The method featured
      a fast and straightforward one-step extraction procedure using
      acetonitrile/water/formic acid (99:33:1, v/v/v) without further cleanup. Rapid LC
      separation in 8min was successfully achieved on a Phenomenex Kinetex C18 column
      (2.1mm*100mm, 2.6MUm) with a flow rate of 0.30mL/min using a mobile phase of
      water containing 0.1% formic acid and methanol. Simultaneous acquisition was
      performed in the positive and negative ion modes. For some analytes, enhanced
      responses were acquired in negative ion mode (e.g., Zearalenone, alpha-Zearalenol
      and beta-Zearalenol); however, the majority of analytes were monitored in
      positive ion mode with multiple reaction monitoring (MRM). Two MS/MS transitions
      for each analyte were acquired to ensure reliable identification and accurate
      quantification. The method was validated in house through linearity, selectivity,
      precision, and recovery studies. Analytical data were satisfactory with typical
      recoveries of 70-120% and relative standard deviations (RSDs) below 20%. The
      limits of detection (LODs) ranged from 0.01 to 0.25ng/mL, which are below the
      maximum residue levels (MRLs) established by European legislation for mycotoxins
      or pesticides in foods and foodstuffs. Forty-three ginseng samples (ginseng
      (n=30), American ginseng (n=6), red ginseng (n=7)) collected from Chinese markets
      were analyzed and the most frequently detected pesticide was chlorpyrifos with an
      incidence of 97% and ranged from 37.63 to 158.60MUg/kg. Ion ratios, retention
      times and experimental Q/q ratios were also compared with those of the
      corresponding reference standard in order to avoid false-positive results. 

PMID- 24113238
TI  - Design and synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4
      dihydropyridines as small molecule BACE-1 inhibitors.
AB  - Alzheimer disease (AD) is a neuronal dementia for which no treatment has been
      consolidated yet. Major pathologic hallmark of AD is the aggregated extracellular
      amyloid-beta plaques in the brains of disease sufferers. Abeta-peptide is a major
      component of amyloid plaques and is produced from amyloid precursor protein (APP)
      via the proteolysis action. An aspartyl protease known as beta-site amyloid
      precursor protein cleaving enzyme (BACE-1) is responsible for this proteolytic
      action. Distinctive role of BACE-1 in AD pathogenesis has made it a validated
      target to develop anti-Alzheimer agents. Our structure-based virtual screening
      method led to the synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl
      1,4-dihydropyridine BACE-1 inhibitors (6a-6p; in vitro hits). Molecular docking
      and DFT-based ab initio studies using B3LYP functional in association with triple
      zeta basis set (TZV) proposed binding mode and binding energies of ligands in the
      active site of the receptor. In vitro BACE-1 inhibitory activities were
      determined by enzymatic fluorescence resonance energy transfer (FRET) assay. Most
      of the synthesized dihydropyridine scaffolds were active against BACE-1 while 6d,
      6k, 6n and 6a were found to be the most potent molecules with IC50 values of
      4.21, 4.27, 4.66 and 6.78 MUM, respectively. Superior BACE-1 inhibitory
      activities were observed for dihydropyridine derivatives containing
      fused/nonfused thiazole containing groups, possibly attributing to the additional
      interactions with S2-S3 subpocket residues. Relatively reliable correlation
      between calculated binding energies and experimental BACE-1 inhibitory activities
      was achieved (R(2)=0.51). Moreover, compounds 6d, 6k, 6n and 6a exhibited
      relatively no calcium channel blocking activity with regard to nifedipine
      suggesting them as appropriate candidates for further modification(s) to BACE-1
      inhibitory scaffolds.

PMID- 24113239
TI  - 5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2.
AB  - Based on previous reports of certain 5-deazaflavin derivatives being capable of
      activating the tumour suppressor p53 in cancer cells through inhibition of the
      p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity
      relationship (SAR) analysis through systematic modification of the 5-deazaflavin
      template. This analysis shows that HDM2-inhibitory activity depends on a
      combination of factors. The most active compounds (e.g., 15) contain a
      trifluoromethyl or chloro substituent at the deazaflavin C9 position and this
      activity depends to a large extent on the presence of at least one additional
      halogen or methyl substituent of the phenyl group at N10. Our SAR results, in
      combination with the HDM2 RING domain receptor recognition model we present, form
      the basis for the design of drug-like and potent activators of p53 for potential
      cancer therapy. 

PMID- 24113240
TI  - Acidic biphenyl derivatives: synthesis and biological activity of a new series of
      potent 5-HT(4) receptor antagonists.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the
      central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin
      mediates a positive chronotropic and inotropic response through 5-HT4 receptors
      in the atrium and ventricle of the heart. Recent investigations have revealed
      increased expression of the 5-HT4(b) isoform in cardiomyocytes of chronic
      arrhythmic and failing hearts, and that the use of 5-HT4 receptor antagonists may
      be beneficial for treating these conditions. The 5-HT4 receptor possesses a
      transmembrane (TM) binding site important for ligand affinity and recognition, as
      well as a capacity to accommodate bulky ligands. A new series of peripherally
      acting 5-HT4 receptor antagonists were prepared by combining the acidic biphenyl
      group from the class of angiotensin II receptor blockers (ARBs) with the SB207266
      (piboserod) scaffold. The new compounds were pharmacologically evaluated and
      carboxylic acid 21 was identified as a potent and promising 5-HT4 receptor
      antagonist with moderate affinity for the AT1 receptor. The permeability of
      carboxylic acid 21 in a Caco-2 assay was low and the corresponding prodrug esters
      23a-f were therefore prepared. The pharmacokinetics of methyl ester 20 and n
      butyl ester 23c were evaluated in a rat model, revealing incomplete metabolism to
      carboxylic acid 21. However, methyl ester 20 is a potent 5-HT4 receptor
      antagonist with binding affinities in the low picomolar range. Methyl ester 20
      has promising oral bioavailability and pharmacokinetics and may target 5-HT4
      receptors in both CNS and peripheral organs. 

PMID- 24113241
TI  - Recession depression: mental health effects of the 2008 stock market crash.
AB  - Do sudden, large wealth losses affect mental health? We use exogenous variation
      in the interview dates of the 2008 Health and Retirement Study to assess the
      impact of large wealth losses on mental health among older U.S. adults. We
      compare cross-wave changes in wealth and mental health for respondents
      interviewed before and after the October 2008 stock market crash. We find that
      the crash reduced wealth and increased feelings of depression and use of
      antidepressant drugs, and that these effects were largest among respondents with
      high levels of stock holdings prior to the crash. These results suggest that
      sudden wealth losses cause immediate declines in subjective measures of mental
      health. However, we find no evidence that wealth losses lead to increases in
      clinically-validated measures of depressive symptoms or indicators of depression.

PMID- 24113243
TI  - Surgical treatment of injuries caused by fishing gear in the intracoelomic
      digestive tract of sea turtles.
AB  - We report the surgical techniques used to remove accidentally ingested hooks and
      branchlines localized in different parts of the digestive tract of 129 loggerhead
      sea turtles Caretta caretta, together with the characteristics and localization
      of lesions, and final outcome related to their severity. Hooks were removed from
      the cervical esophagus via the ventral surface of the neck, while the
      supraplastron approach was performed for hooks wedged in the intracoelomic
      portion of the esophagus. An approach through the left axillary region was
      preferred for fishhooks in the stomach, while hooks and long branchlines in the
      intestine or pyloric area were removed by approaching the coelomic cavity through
      the right or left prefemoral fossa. The ingestion of fishhooks, and/or longlines,
      often induces severe injuries in the digestive tract that could lead to the death
      of the turtles, with the extent of damage engendered by lines often more severe
      than that caused by hooks, leading to strangulation, intussusception, and tears
      that require resection of long tracts of intestine. Spontaneous expulsion of
      hooks, even where possible, involves long waiting times, with the possible
      impairment of the turtle's clinical condition, and should be avoided when the
      line is evident or suspected. The development of diversified surgical techniques
      enabled us to approach the coelomic cavity with minimally invasive and easy-to
      perform methods, and survival rates proved very satisfactory. 

PMID- 24113244
TI  - Universal reverse-transcriptase real-time PCR for infectious hematopoietic
      necrosis virus (IHNV).
AB  - Infectious hematopoietic necrosis virus (IHNV) is an acute pathogen of salmonid
      fishes in North America, Europe and Asia and is reportable to the World
      Organization for Animal Health (OIE). Phylogenetic analysis has identified 5
      major virus genogroups of IHNV worldwide, designated U, M, L, E and J; multiple
      subtypes also exist within those genogroups. Here, we report the development and
      validation of a universal IHNV reverse-transcriptase real-time PCR (RT-rPCR)
      assay targeting the IHNV nucleocapsid (N) gene. Properties of diagnostic
      sensitivity (DSe) and specificity (DSp) were defined using laboratory-challenged
      steelhead trout Oncorhynchus mykiss, and the new assay was compared to the OIE
      accepted conventional PCR test and virus isolation in cell culture. The IHNV N
      gene RT-rPCR had 100% DSp and DSe and a higher estimated diagnostic odds ratio
      (DOR) than virus culture or conventional PCR. The RT-rPCR assay was highly
      repeatable within a laboratory and highly reproducible between laboratories.
      Field testing of the assay was conducted on a random sample of juvenile steelhead
      collected from a hatchery raceway experiencing an IHN epizootic. The RT-rPCR
      detected a greater number of positive samples than cell culture and there was 40%
      agreement between the 2 tests. Overall, the RT-rPCR assay was highly sensitive,
      specific, repeatable and reproducible and is suitable for use in a diagnostic
      setting. 

PMID- 24113245
TI  - Characterization of perch rhabdovirus (PRV) in farmed grayling Thymallus
      thymallus.
AB  - Two Finnish fish farms experienced elevated mortality rates in farmed grayling
      Thymallus thymallus fry during the summer months, most typically in July. The
      mortalities occurred during several years and were connected with a few
      neurological disorders and peritonitis. Virological investigation detected an
      infection with an unknown rhabdovirus. Based on the entire glycoprotein (G) and
      partial RNA polymerase (L) gene sequences, the virus was classified as a perch
      rhabdovirus (PRV). Pairwise comparisons of the G and L gene regions of grayling
      isolates revealed that all isolates were very closely related, with 99 to 100%
      nucleotide identity, which suggests the same origin of infection. Phylogenetic
      analysis demonstrated that they were closely related to the strain isolated from
      perch Perca fluviatilis and sea trout Salmo trutta trutta caught from the Baltic
      Sea. The entire G gene sequences revealed that all Finnish grayling isolates, and
      both the perch and sea trout isolates, were most closely related to a PRV
      isolated in France in 2004. According to the partial L gene sequences, all of the
      Finnish grayling isolates were most closely related to the Danish isolate DK5533
      from pike. The genetic analysis of entire G gene and partial L gene sequences
      showed that the Finnish brown trout isolate ka907_87 shared only approximately 67
      and 78% identity, respectively, with our grayling isolates. The grayling isolates
      were also analysed by an immunofluorescence antibody test. This is the first
      report of a PRV causing disease in grayling in Finland. 

PMID- 24113242
TI  - The antimalarial amodiaquine causes autophagic-lysosomal and proliferative
      blockade sensitizing human melanoma cells to starvation- and chemotherapy-induced
      cell death.
AB  - Pharmacological inhibition of autophagic-lysosomal function has recently emerged
      as a promising strategy for chemotherapeutic intervention targeting cancer cells.
      Repurposing approved and abandoned non-oncological drugs is an alternative
      approach to the identification and development of anticancer therapeutics, and
      antimalarials that target autophagic-lysosomal functions have recently attracted
      considerable attention as candidates for oncological repurposing. Since
      cumulative research suggests that dependence on autophagy represents a specific
      vulnerability of malignant melanoma cells, we screened a focused compound library
      of antimalarials for antimelanoma activity. Here we report for the first time
      that amodiaquine (AQ), a clinical 4-aminoquinoline antimalarial with unexplored
      cancer-directed chemotherapeutic potential, causes autophagic-lysosomal and
      proliferative blockade in melanoma cells that surpasses that of its parent
      compound chloroquine. Monitoring an established set of protein markers (LAMP1,
      LC3-II, SQSTM1) and cell ultrastructural changes detected by electron microscopy,
      we observed that AQ treatment caused autophagic-lysosomal blockade in malignant
      A375 melanoma cells, a finding substantiated by detection of rapid inactivation
      of lysosomal cathepsins (CTSB, CTSL, CTSD). AQ-treatment was associated with
      early induction of energy crisis (ATP depletion) and sensitized melanoma cells to
      either starvation- or chemotherapeutic agent-induced cell death. AQ displayed
      potent antiproliferative effects, and gene expression array analysis revealed
      changes at the mRNA (CDKN1A, E2F1) and protein level (TP53, CDKN1A, CCND1,
      phospho-RB1 [Ser 780]/[Ser 807/811], E2F1) consistent with the observed
      proliferative blockade in S-phase. Taken together, our data suggest that the
      clinical antimalarial AQ is a promising candidate for repurposing efforts that
      aim at targeting autophagic-lysosomal function and proliferative control in
      malignant melanoma cells. 

PMID- 24113246
TI  - Identification of an iron acquisition machinery in Flavobacterium columnare.
AB  - Flavobacterium columnare, a fastidious Gram-negative pathogen and the causative
      agent of columnaris disease, is one of the most harmful pathogens in the
      freshwater fish-farming industry. Nevertheless the virulence mechanisms of F.
      columnare are not well understood. Bacterial iron uptake from the host during
      infection is an important mechanism of virulence. Here we identified and analyzed
      part of the iron uptake machinery of F. columnare. Under iron-limited conditions
      during in vitro growth, synthesis of an outer membrane protein of ~86 kDa was
      upregulated. This protein was identified as a TonB-dependent ferrichrome-iron
      receptor precursor (FhuA). Synthesis of siderophores in F. columnare was
      corroborated by chrome azurol S assays. A putative ferric uptake regulator (Fur)
      protein was also identified in the F. columnare genome. Structural analysis of
      the F. columnare Fur protein revealed that it was similar to Fur proteins
      involved in iron uptake regulation of other bacteria. Furthermore, Salmonella
      enterica serovar Typhimurium (S. Typhimurium) Deltafur mutants were partially
      complemented by the F. columnare fur gene. We conclude that a siderophore
      mediated iron uptake system exists in F. columnare, and fur from F. columnare
      could partially complement S. Typhimurium Deltafur mutant. 

PMID- 24113247
TI  - Population model for Amyloodinium ocellatum infecting the spotted seatrout
      Cynoscion nebulosus and the red snapper Lutjanus campechanus.
AB  - The dinoflagellate Amyloodinium ocellatum, a major pathogen in warm water
      mariculture, has a trophont, a tomont and a dinospore life history stage. This
      paper presents a population model for A. ocellatum infecting spotted seatrout
      Cynoscion nebulosus and red snapper Lutjanus campechanus and evaluates the
      relative effect of each vital rate on the A. ocellatum population growth rate.
      The vital rates were estimated by incubating trophonts in vitro and tracking
      their development through the successive life history stages at 25 degrees C and
      33 ppt. The A. ocellatum population growth rate was 1.90 d-1 for spotted seatrout
      and 1.92 d-1 for red snapper. Highest elasticity values (0.24 and 0.23 in spotted
      seatrout and red snapper, respectively) corresponded to transitions from the
      dinospore to the trophont stage, the trophont stage to the tomont stage and the
      tomont stage back to the dinospore stage in both host species (self-loops not
      included). A 50% change in vital rates showed that the mean number of dinospores
      produced by a tomont had the largest effect on the A. ocellatum population growth
      rate (15%), followed by the dinospore infection rate (14%), the tomont
      sporulation rate (12%) and the dinospore mortality rate (10%) in both host
      species. A comparison of modeled and experimental vital rate threshold values
      revealed a 2.5- (spotted seatrout) or a 2.6-fold (red snapper) difference in the
      values for dinospore mortality, which is the smallest difference among all the
      modeled and experimental vital rates. Therefore, measures that increase dinospore
      mortality have a greater likelihood of influencing the outcome of an epidemic. 

PMID- 24113248
TI  - Antigenic characterization of Enteromyxum leei (Myxozoa: Myxosporea).
AB  - Enteromyxum leei, an intestinal myxozoan parasite affecting a wide range of fish,
      was partially purified, and the immunogenic composition of its glycoproteins as
      well as the proteolytic activity were studied. Parasite extracts, mainly
      containing spores, were separated by SDS-PAGE, and thereafter, immunoblots were
      carried out with a polyclonal antiserum (Pab) raised against E. leei. Periodic
      acid/Schiff staining of gels, periodate- and Proteinase K-treated Western blots
      and Lectin blots were performed to analyse the terminal carbohydrate composition
      of the parasite's antigens. Additionally, the cross-reaction of the parasite
      extracts with a Pab raised against the polar filament of the myxozoan Myxobolus
      pendula was studied. Both Pabs detected proteic epitopes on antigenic proteins
      and glycoproteins of E. leei, ranging between 15 and 280 kDa. In particular, 2
      glycoproteic bands (15 and 165 kDa), immunoreactive to both Pabs and with glucose
      and mannose moieties, could correspond to common antigens shared among myxozoans.
      The 165 kDa band also presented galactose, N-acetyl-galactosamine and N-acetyl
      glucosamine, pointing to its possible origin on chitin-built spore valves and to
      its possible involvement in host-parasite interactions. The molecular weight of
      the 15 kDa glycoproteic antigen matches that of minicollagen, a cnidarian
      specific protein of nematocysts with a myxozoan homologue. Several proteases with
      apparent molecular weights ranging between 43 and 245 kDa were found in
      zymographies of E. leei extracts, and these may have a potential role in the
      parasite's pathogenesis. This is a useful approach for further studies to detect
      targets for antiparasitic therapy. 

PMID- 24113249
TI  - Postmonorchis sp. inq. (Digenea: Monorchiidae) metacercariae infecting natural
      beds of wedge clam Donax trunculus in Italy.
AB  - The wedge clam Donax trunculus Linnaeus, 1758 is one of the most common bivalve
      molluscs inhabiting the sandy shores of the Mediterranean Sea and is considered
      an important commercial resource. In this study, we report the first molecular,
      morphological and histopathological descriptions of metacercariae from a
      trematode belonging to the genus Postmonorchis (Digenea: Monorchiidae) that
      infects D. trunculus in natural beds of the Italian Tyrrhenian coast (Campania,
      Lazio and Tuscany). Morphological analysis of the parasite revealed a combination
      of features that exist in the 3 previously identified species of Postmonorchis,
      viz. P. donacis, P. variabilis and P. orthopristis, with the addition of new,
      distinctive morphological characteristics. The pathogen exhibited a predilection
      for the gill; however, it was also present in the labial palp and mantle in
      addition to the gut, kidney epithelium and foot. The inflammatory response was
      characterised by either a focal or diffuse haemocyte infiltration followed by the
      formation of multiple, large multi-layered capsules associated with tissue
      destruction. The prevalence of the pathogen ranged from 75 to 100%, while the
      infection intensity fluctuated among the study areas. Further studies regarding
      the life cycle of this parasite and the identification of other larval and adult
      stages and their respective hosts may confirm the identification of a new species
      of Postmonorchis that infects wedge clams in Mediterranean waters. The study of
      the parasite is completed by molecular analysis of the ITS1 and ITS2 rDNA
      sequences. 

PMID- 24113250
TI  - Detection of Bonamia exitiosa (Haplosporidia) in European flat oysters Ostrea
      edulis cultivated in mainland Britain.
AB  - Following a reported mortality event of European flat oysters Ostrea edulis in
      southwestern England in December 2010, a sample of 30 oysters was examined using
      histology and molecular techniques. Histological examination of the oysters
      revealed the presence of microcell stages in the haemocytes and connective
      tissues of 3 out of the 30 animals examined. One animal showing marked haemocyte
      infiltration of the connective tissues was considered to be infected with Bonamia
      ostreae based on the presence of small uninucleate microcells measuring
      approximately 1 to 1.5 um in diameter. Two other oysters were considered by
      histology to be infected with B. exitiosa. Infected haemocytes contained up to 5
      microcells, measuring approximately 2 to 3 um in diameter with a central or
      subcentral nucleus. Rarely, larger plasmodia-like multinucleated stages were
      noted in the haemocyte cytoplasm characterised by its irregular shape and
      increased eosinophilic cytoplasm. Haemocyte infiltration of the connective
      tissues surrounding the digestive gland and the mantle was noted along with
      necrosis of the tissues associated with the infection. Molecular analysis of the
      infected animals confirmed the presence of B. exitiosa in the sample. This study
      describes the parasite from flat oysters cultured in the UK; subsequent targeted
      sampling has not detected the parasite in flat oyster populations at this or
      other sites within the UK. 

PMID- 24113251
TI  - Contrasting recovery following removal of growth anomalies in the corals Acropora
      and Montipora.
AB  - Growth anomalies (GAs) in scleractinian corals drain energy from the host and can
      result in partial or entire colony mortality. Here I show that growth anomaly
      removal is an effective treatment for the branching coral Acropora acuminata,
      with 90% of subjects remaining GA-free 9 mo following the procedure. In contrast,
      the encrusting coral Montipora efflorescens did not respond positively to
      treatment, with GAs re-developing in 100% of treated subjects. There was no clear
      evidence that injuries sustained during GA removal increased susceptibility to GA
      development in either coral species. Based on these results, I hypothesize that
      the factors inducing GAs in Acropora acuminata are localized, whereas those in
      Montipora efflorescens appear more systemic throughout the colony-perhaps the
      result of a genetically-based factor, or a persistent causative agent such as a
      virus. GA removal may therefore be effective for targeted rescues of particular
      coral species and morphologies in reef systems with low overall disease
      prevalence and is likely to be most effective for scleractinian corals if
      complimented by management actions that address the ultimate drivers of GAs on
      coral reefs. 

PMID- 24113252
TI  - Sensor arrays from multicomponent micropatterned nanoparticles and graphene.
AB  - A novel approach for multicomponent patterning metal/metal oxide nanoparticles on
      graphene was developed, which involves region-specific plasma treatment, followed
      by region-selective substrate-enhanced electroless deposition of Au nanoparticles
      and solution alkalization of ferrous chloride tetrahydrate in the presence of
      ammonia into Fe3O4 nanoparticles. The resultant Fe3O4/Au multicomponent
      micropatterned-graphene films were found to be highly selective sensor arrays for
      detecting low levels of chemical vapor molecules at ppm levels. This novel
      concept could be applied to the development of various multicomponent patterned
      nanomaterials for many potential applications, ranging from nanoscale region
      specific chemical-/bio-sensor arrays to multifunctional optoelectronic devices. 

PMID- 24113253
TI  - Facile synthesis of trifluoroethyl compounds by the Suzuki cross-coupling
      reactions of CF3CH2OTs with arylboronic acids.
AB  - This research provides a novel approach for introducing a CF3CH2 group onto
      aromatic rings using Pd(OAc)2/palladacycle as a catalyst for the Suzuki cross
      coupling reaction of CF3CH2OTs (OTs = 4-methylbenzene sulfonate) with arylboronic
      acids. 

PMID- 24113255
TI  - The case for an electronic fetal heart rate monitoring credentialing examination.
AB  - The Perinatal Quality Foundation has created an examination containing both
      knowledge-based and judgment questions relating to the interpretation of
      electronic fetal heart rate monitoring for credentialing all medical and nursing
      personnel working on a labor and delivery floor. A description of the examination
      and the rationale for its use throughout the United States is presented. 

PMID- 24113256
TI  - Perinatal psychiatric disorders: an overview.
AB  - Perinatal mental illness has a significant implication on maternal health, birth
      outcomes, and the offspring's development. Prevalence estimates of perinatal
      psychiatric illnesses range widely, with substantial heterogeneity in different
      population studies, with a lower prevalence rate in high- rather than low- or
      middle-income countries. Because of the potential negative impact on maternal and
      child outcomes and the potential lability of these disorders, the perinatal
      period is a critical time to identify psychiatric illnesses. Thus, obstetricians
      and midwives play a crucial role in assessing women's mental health needs and to
      refer identified women promptly for multidisciplinary specialist assessment.
      However, there is still limited evidence on best practice assessment and
      management policies during pregnancy and postpartum. This review focuses on the
      prevalence of common perinatal mental disorders and antenatal screening policies
      to identify women at risk. The effect of these conditions and their management on
      pregnancy, fetal outcomes, and child development are discussed. 

PMID- 24113254
TI  - Relationship between 17-alpha hydroxyprogesterone caproate concentration and
      spontaneous preterm birth.
AB  - OBJECTIVE: 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent
      spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%.
      The dose is not based on pharmacologic considerations. A therapeutic
      concentration has not been determined hampering any attempt to optimize
      treatment. This study evaluated the relationship between 17-alpha
      hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous
      preterm birth in women with singleton gestation. STUDY DESIGN: A single blood
      sample was obtained between 25 and 28 weeks' gestation from 315 women with a
      spontaneous preterm birth who participated in a placebo-controlled, prospective,
      randomized clinical trial evaluating the benefit of omega-3 supplementation in
      reducing preterm birth. All women in the parent study received 17-alpha
      hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418
      received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha
      hydroxyprogesterone caproate concentration. RESULTS: There were no differences
      between placebo and omega-3 supplemented groups in demographic variables,
      outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma
      concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL.
      Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the
      lowest quartile had a significantly higher risk of spontaneous preterm birth (P =
      .03) and delivered at significantly earlier gestational ages (P = .002) than did
      women in the second to fourth quartiles. The lowest preterm birth rates were seen
      when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4
      ng/mL. CONCLUSION: Low plasma 17-alpha hydroxyprogesterone caproate concentration
      is associated with an increased risk of spontaneous preterm birth. This finding
      validates efficacy of this treatment but suggests that additional studies are
      needed to determine the optimal dosage.

PMID- 24113257
TI  - Making valid causal inferences from observational data.
AB  - The ability to make strong causal inferences, based on data derived from outside
      of the laboratory, is largely restricted to data arising from well-designed
      randomized control trials. Nonetheless, a number of methods have been developed
      to improve our ability to make valid causal inferences from data arising from
      observational studies. In this paper, I review concepts of causation as a
      background to counterfactual causal ideas; the latter ideas are central to much
      of current causal theory. Confounding greatly constrains causal inferences in all
      observational studies. Confounding is a biased measure of effect that results
      when one or more variables, that are both antecedent to the exposure and
      associated with the outcome, are differentially distributed between the exposed
      and non-exposed groups. Historically, the most common approach to control
      confounding has been multivariable modeling; however, the limitations of this
      approach are discussed. My suggestions for improving causal inferences include
      asking better questions (relates to counterfactual ideas and "thought" trials);
      improving study design through the use of forward projection; and using
      propensity scores to identify potential confounders and enhance exchangeability,
      prior to seeing the outcome data. If time-dependent confounders are present (as
      they are in many longitudinal studies), more-advanced methods such as marginal
      structural models need to be implemented. Tutorials and examples are cited where
      possible. 

PMID- 24113258
TI  - Non-neuronal cell responses differ between normal and Down syndrome developing
      brains.
AB  - Down syndrome (DS), the most common genetic cause of mental retardation, is
      characterized by reduced number of neurons and delayed myelination. Though non
      neuronal cells in the brain are vital for the development, survival, and function
      of neurons, there is a paucity of comparative studies of normal development and
      DS, in particular in the temporal lobe, a region of interest for cognitive
      decline. We evaluated immunoreactivity for CD68 (macrophage), HLA-DR (microglia),
      Olig2 and TPPP/p25 (oligodendroglia), and GFAP (astroglia) in the germinal matrix
      (GM), temporal lobe white matter (TeWM) and hippocampus from 14 weeks of
      gestations to newborn in 28 DS patients and 30 age-matched controls. The rate of
      increase of CD68 positive cells in the GM, CA1 hippocampal subregion and
      subiculum was significantly higher in DS. The density of Olig2 positive cells in
      the GM was lower in DS brains at early stages, then showed a transient increase
      contrasting controls. Olig2 expression increased more in the TeWM in DS,
      suggesting an altered pattern of oligodendrocyte progenitor generation. GFAP
      immunoreactivity in DS was significantly lower in the middle pregnancy period in
      the TeWM and did not increase between early and middle periods in the GM compared
      to controls, likely reflecting a defect in astrocyte production. The altered
      expression of non-neuronal cell markers during normal development and DS may play
      a role in, or reflect, defective neurogenesis, leading to reduced number of
      neurons and delayed myelination in the developing DS brain. This has implications
      for the understanding of the mental retardation in DS patients. 

PMID- 24113259
TI  - The role of ERK1/2 in the regulation of proliferation and differentiation of
      astrocytes in developing brain.
AB  - Extracellular signal regulated kinases (ERK) are important components of the Ras
      Raf-MEK-ERK signaling pathway cascades that mediate intracellular stimuli
      transduction and gene expression. ERK1 (44kDa) and ERK2 (42kDa) are homologous
      subtypes of the ERK family, which participate in regulation of a variety of cell
      activities, including cell proliferation, migration and differentiation,
      especially in the central nervous systerm (CNS). Hence, they exert critical
      effects on neuron and astrocyte development. Astrocytes are critically involved
      in maintaining CNS homeostasis and supporting neuron growth. When exposed to an
      extracellular stimulus, such as inflammation or oxidative stress, the
      corresponding cell response can be regulated by the ERK1/2 signaling pathway.
      Furthermore, several lines of evidence have demonstrated a correlation between
      astrocyte activity and the Ras-Raf-MEK-ERK signaling pathway. However many
      questions remain unanswered regarding the role of ERK1/2 in astrocyte
      development. This review summarizes the possible role of ERK1/2 signaling
      cascades in modulating the proliferation, differentiation and apoptosis of
      astrocytes in both physiological and pathological conditions. In addition, this
      review also briefly elucidates the participation of ERK1/2 in the process of
      human brain glia tumor oncogenesis and metastasis, which will provide some
      concepts for treatment strategies to delay the process of tumor evolution. 

PMID- 24113260
TI  - Comparison of influenza virus yields and apoptosis-induction in an adherent and a
      suspension MDCK cell line.
AB  - Cell culture-based manufacturing of influenza vaccines is ideally based on easily
      scalable platforms using suspension cells that grow in chemically defined media.
      Consequently, different adherent cell lines selected for high virus yields were
      adapted to grow in suspension culture. This includes the MDCK suspension cell
      line MDCK.SUS2, which was shown to be a suitable substrate for influenza virus
      propagation in previous studies. In this study, we investigated options for
      further improvement of influenza A/PR/8 (H1N1) virus titres and cell-specific
      virus yields. Best results were achieved by performing a 1:2 dilution with fresh
      medium at time of infection. In shake flask cultivations, even for multiplicities
      of infection as low as 10-5, all cells were infected at 36 h post infection as
      determined by flow cytometry. In addition, these cells showed a better viability
      than cells infected without previous washing steps, which was reflected by a
      reduced level of apoptotic cells, and virus yields exceeding 3 log10 HAU/100 MUL.
      Comparison of bioreactor infections of MDCK.SUS2 cells to the parental adherent
      MDCK cells showed similar HA titres of 2.94 and 3.15 log10 HAU/100 MUL and TCID50
      of 1 * 109 and 2.37 * 109 infectious virions/mL. Surprisingly, virus-induced
      apoptosis differed between the two cell lines, with the MDCK.SUS2 cells showing a
      much stronger apoptosis induction than the adherent MDCK cells. Obviously,
      despite their resistance to anoikis, the suspension cells were more susceptible
      to virus-induced apoptosis. Whether this is related to the adaptation process
      itself and/or to changes in cell survival pathways influenced by adhesion
      molecules or influenza virus proteins needs to be clarified in additional
      studies.

PMID- 24113261
TI  - Recombinant protein YbgF induces protective immunity against Rickettsia
      heilongjiangensis infection in C3H/HeN mice.
AB  - BACKGROUND: Surface proteins YbgF and PrsA are major seroreactive antigens of
      Rickettsia heilongjiangensis, the etiological agent of Far-Eastern spotted fever.
      This study investigated their potential immunogenicity for protective immunity.
      METHODS: Recombinant YbgF and PrsA were used to immunize C3H/HeN mice and
      rickettsial loads in immunized mouse organs were assessed after R.
      heilongjiangensis challenge. Anti-sera from immunized mice were applied to
      neutralize rickettsiae. CD4+ and CD8+ T cells isolated from R. heilongjiangensis
      infected mice were stimulated with YbgF or PrsA, and proliferation and cytokine
      production assessed. RESULTS: The IgG2a/IgG1 ratio of sera was markedly increased
      in YbgF-immunized mice but was unaltered in PrsA-immunized mice after
      immunization. The rickettsial load in YbgF-immunized mice was significantly lower
      than in PrsA-immunized mice after R. heilongjiangensis challenge. Incubation with
      anti-serum to YbgF, but not PrsA, significantly reduced the number of rickettsiae
      adhering to and invading endothelial cells. The proliferation level and tumor
      necrosis factor-alpha secretion level of CD4+ T cells from R. heilongjiangensis
      infected mice were significantly higher than in uninfected mice after stimulation
      with YbgF but not PrsA. CONCLUSION: YbgF is a novel protective antigen that
      induces a Th1-type of protective immune response against R. heilongjiangensis
      infection.

PMID- 24113262
TI  - Appendiceal actinomycosis complicated by multiple hepatic abscesses.
AB  - We report the case of a patient with appendicitis due to actinomycosis,
      complicated by multiple liver abscesses. Definitive diagnosis was based on
      histopathologic examination of the resected appendix. Accurate identification of
      the pathogen led to curative antibiotic therapy of the liver abscesses. 

PMID- 24113263
TI  - A randomized trial of calorie labeling on menus.
AB  - BACKGROUND: Food consumed outside the home accounts for a growing proportion of
      the North American diet and has been associated with increased obesity. PURPOSE:
      To examine the effect of nutrition labeling on menus on awareness, use, and food
      consumption, including the impact of "traffic light" labeling and adding other
      nutrients. METHODS: Blinded, randomized trial with 635 Canadian adults conducted
      in 2010-2011. Participants ordered a free meal from one of four experimental
      menus: 1) no nutritional information shown, 2) calorie amounts only, 3) calorie
      amounts in "traffic lights", and 4) calorie, fat, sodium, and sugar shown in
      "traffic lights". Recall of nutrition information, knowledge of calorie content
      and nutrient consumption were assessed. RESULTS: Participants in the calorie
      conditions were more likely to recall the calorie content of meals and to report
      using nutrition information when ordering. The calorie content of meals was not
      significantly different across conditions; however, calorie consumption was
      significantly lower among participants in the Calorie-only condition compared to
      the No information condition (mean=-96 kcal, p=.048). CONCLUSIONS: Menu labeling
      increased awareness and use of nutrition information and reduced consumption.
      Adding "traffic lights", fat, sodium, and sugar amounts to menus had little
      impact compared to calorie-only labeling.

PMID- 24113266
TI  - Administrative issues to ensure safe anesthesia care in the office-based setting.
AB  - PURPOSE OF REVIEW: Office-based practice is distinct from other ambulatory
      practices and has unique considerations for an effective administrative structure
      to support its operations. RECENT FINDINGS: National guidelines have been
      promulgated by various entities addressing both management and clinical care
      aspects of the practice. Specific regulations vary by practice location, and
      practitioners need to comply with the pertinent accreditation and licensing
      requirements. Anesthesiologists have been at the forefront of promoting the
      culture of safety in the office-based setting. Specific practice considerations
      include provider credentialing, maintenance of documentation, quality assessment,
      professional liability, facility safety, patient health information, billing, and
      finance. Although there is emerging literature linking office accreditation to
      improved patient outcomes, more work is needed in this area. SUMMARY: Office
      based practice will continue to evolve with the national emphasis on patient
      safety, cost reduction, value-based care, and outcomes measurement and reporting.
      Each practice must comply with the state and national regulations that could
      limit the types of procedures being performed and who can administer sedation or
      anesthesia, and require the facility to be accredited by a nationally recognized
      accrediting agency.

PMID- 24113265
TI  - Beyond crisis resource management: new frontiers in human factors training for
      acute care medicine.
AB  - PURPOSE OF REVIEW: Error is ubiquitous in medicine, particularly during critical
      events and resuscitation. A significant proportion of adverse events can be
      attributed to inadequate team-based skills such as communication, leadership,
      situation awareness and resource utilization. Aviation-based crisis resource
      management (CRM) training using high-fidelity simulation has been proposed as a
      strategy to improve team behaviours. This review will address key considerations
      in CRM training and outline recommendations for the future of human factors
      education in healthcare. RECENT FINDINGS: A critical examination of the current
      literature yields several important considerations to guide the development and
      implementation of effective simulation-based CRM training. These include defining
      a priori domain-specific objectives, creating an immersive environment that
      encourages deliberate practice and transfer-appropriate processing, and the
      importance of effective team debriefing. Building on research from high-risk
      industry, we suggest that traditional CRM training may be augmented with new
      training techniques that promote the development of shared mental models for team
      and task processes, address the effect of acute stress on team performance, and
      integrate strategies to improve clinical reasoning and the detection of cognitive
      errors. SUMMARY: The evolution of CRM training involves a 'Triple Threat'
      approach that integrates mental model theory for team and task processes,
      training for stressful situations and metacognition and error theory towards a
      more comprehensive training paradigm, with roots in high-risk industry and
      cognitive psychology. Further research is required to evaluate the impact of this
      approach on patient-oriented outcomes.

PMID- 24113264
TI  - Regional anesthesia and ambulatory surgery.
AB  - PURPOSE OF REVIEW: Advances in surgery and anesthesia have allowed for more
      surgeries to be done on an outpatient basis. A recent important advance entails
      availability of suitable recovery criteria to capitalize on the benefits of
      regional anesthesia for ambulatory surgery. With ever-escalating healthcare costs
      and expectations for faster recovery, anesthesiologists are now challenged to
      design anesthesia plans focused on Phase I postanesthesia care unit bypass and
      early facility discharge. Satisfying the recently published WAKE Score criteria
      upon operating room exit is associated with hospital cost reductions. This review
      highlights regional anesthesia techniques with focus on outpatient orthopedics.
      We also discuss 'multimodalities' addressing postoperative nausea and vomiting
      prophylaxis, perioperative analgesia (including perineural analgesia), and
      sedation-hypnosis, which are all central to timely recovery using now-available
      suitable recovery criteria. RECENT FINDINGS: Ultrasound-guided regional
      anesthesia has increased the comfort level for many anesthesiologists performing
      blocks. Other advances include better monitoring of anesthetic depth for
      titration of sedatives, en route to avoiding emetogenic and hyperalgesic volatile
      anesthetics. SUMMARY: Routine regional anesthesia use, multimodal postoperative
      nausea and vomiting prophylaxis, multimodal sedation-hypnosis, and multimodal
      analgesia, along with avoiding volatile agents and short-duration opioids, can
      lead to both routine Phase 1 postanesthesia care unit bypass and expedited same
      day discharge, when using suitable recovery criteria.

PMID- 24113267
TI  - The use of simulation in teaching the basic sciences.
AB  - PURPOSE OF REVIEW: To assess the current use of simulation in medical education,
      specifically, the teaching of the basic sciences to accomplish the goal of
      improved integration. RECENT FINDINGS: Simulation is increasingly being used by
      the institutions to teach the basic sciences. Preliminary data suggest that it is
      an effective tool with increased retention and learner satisfaction. SUMMARY:
      Medical education is undergoing tremendous change. One of the directions of that
      change is increasing integration of the basic and clinical sciences to improve
      the efficiency and quality of medical education, and ultimately to improve the
      patient care. Integration is thought to improve the understanding of basic
      science conceptual knowledge and to better prepare the learners for clinical
      practice. Simulation because of its unique effects on learning is currently being
      successfully used by many institutions as a means to produce that integration
      through its use in the teaching of the basic sciences. Preliminary data indicate
      that simulation is an effective tool for basic science education and garners high
      learner satisfaction.

PMID- 24113268
TI  - Threat and error management for anesthesiologists: a predictive risk taxonomy.
AB  - PURPOSE OF REVIEW: Patient care in the operating room is a dynamic interaction
      that requires cooperation among team members and reliance upon sophisticated
      technology. Most human factors research in medicine has been focused on analyzing
      errors and implementing system-wide changes to prevent them from recurring. We
      describe a set of techniques that has been used successfully by the aviation
      industry to analyze errors and adverse events and explain how these techniques
      can be applied to patient care. RECENT FINDINGS: Threat and error management
      (TEM) describes adverse events in terms of risks or challenges that are present
      in an operational environment (threats) and the actions of specific personnel
      that potentiate or exacerbate those threats (errors). TEM is a technique widely
      used in aviation, and can be adapted for the use in a medical setting to predict
      high-risk situations and prevent errors in the perioperative period. A threat
      taxonomy is a novel way of classifying and predicting the hazards that can occur
      in the operating room. TEM can be used to identify error-producing situations,
      analyze adverse events, and design training scenarios. SUMMARY: TEM offers a
      multifaceted strategy for identifying hazards, reducing errors, and training
      physicians. A threat taxonomy may improve analysis of critical events with
      subsequent development of specific interventions, and may also serve as a
      framework for training programs in risk mitigation.

PMID- 24113269
TI  - Anesthesia education across borders.
AB  - PURPOSE OF REVIEW: Changing attitudes toward global health are affecting medical
      education programs at all levels in the USA and abroad. This review describes
      some of these changes, and how these affect the educational aspects of US global
      health programs and anesthesia training in developing countries. RECENT FINDINGS:
      Interest in global health has surged in the past decade, and support for programs
      has increased in medical schools, university hospitals and from the US
      government. Recognition of the surgical burden of disease as a global public
      health problem has been slow but is also increasing. Anesthesia involvement in
      building healthcare education infrastructure and workforce in low-resource
      countries is needed and important, and benefits can be had on both sides of the
      border. SUMMARY: The past 5 years have brought a new global focus on workforce
      development and education in anesthesia. Programs need to be supported by all
      stakeholders and monitored for safety, quality and outcomes.

PMID- 24113270
TI  - Introduction to the 2013 ambulatory anesthesia series.

PMID- 24113271
TI  - Aspirin-induced Bcl-2 translocation and its phosphorylation in the nucleus
      trigger apoptosis in breast cancer cells.
AB  - Here, we report that B-cell lymphoma 2 (Bcl-2) is a novel target molecule of
      aspirin in breast cancer cells. Aspirin influenced the formation of a complex by
      Bcl-2 and FKBP38 and induced the nuclear translocation of Bcl-2 and its
      phosphorylation. These events inhibited cancer cell proliferation and
      subsequently enhanced MCF-7 breast cancer cell apoptosis. Bcl-2 knockdown using
      small interfering RNA (siRNA) delayed apoptotic cell death, which correlated with
      increased proliferation following aspirin exposure. In contrast, Bcl-2
      overexpression enhanced the onset of aspirin-induced apoptosis, which was also
      associated with a significant increase in Bcl-2 phosphorylation in the nucleus.
      Therefore, this study may provide novel insight into the molecular mechanism of
      aspirin, particularly its anticancer effects in Bcl-2- and estrogen receptor
      positive breast cancer cells. 

PMID- 24113272
TI  - Discriminant analysis of prion sequences for prediction of susceptibility.
AB  - Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE),
      human kuru and Creutzfeldt-Jakob disease (CJD), originate from a conformational
      change of the normal cellular prion protein (PrP(C)) into abnormal protease
      resistant prion protein (PrP(Sc)). There is concern regarding these prion
      diseases because of the possibility of their zoonotic infections across species.
      Mutations and polymorphisms of prion sequences may influence prion-disease
      susceptibility through the modified expression and conformation of proteins.
      Rapid determination of susceptibility based on prion-sequence polymorphism
      information without complex structural and molecular biological analyses may be
      possible. Information regarding the effects of mutations and polymorphisms on
      prion-disease susceptibility was collected based on previous studies to classify
      the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the
      position-specific scoring matrix were utilised to determine the distance of
      target sequences. The k-nearest neighbour analysis was validated with cross
      validation methods. The results indicated that the number of polymorphisms did
      not influence prion-disease susceptibility, and three and four k-objects showed
      the best accuracy in identifying the susceptible group. Although sequences with
      negative polymorphisms showed relatively high accuracy for determination,
      polymorphisms may still not be an appropriate factor for estimating variation in
      susceptibility. Discriminant analysis of prion sequences with scoring matrices
      was attempted as a possible means of determining susceptibility to prion
      diseases. Further research is required to improve the utility of this method. 

PMID- 24113273
TI  - A novel instrument for dye injection and aspiration aiding the removal of
      internal limiting membranes and epiretinal membranes.

PMID- 24113274
TI  - Ocriplasmin: a medical or surgical therapy?

PMID- 24113275
TI  - Jazz improvisation, creativity, and brain plasticity.

PMID- 24113276
TI  - Approaching the limit of predictability in human mobility.
AB  - In this study we analyze the travel patterns of 500,000 individuals in Cote
      d'Ivoire using mobile phone call data records. By measuring the uncertainties of
      movements using entropy, considering both the frequencies and temporal
      correlations of individual trajectories, we find that the theoretical maximum
      predictability is as high as 88%. To verify whether such a theoretical limit can
      be approached, we implement a series of Markov chain (MC) based models to predict
      the actual locations visited by each user. Results show that MC models can
      produce a prediction accuracy of 87% for stationary trajectories and 95% for non
      stationary trajectories. Our findings indicate that human mobility is highly
      dependent on historical behaviors, and that the maximum predictability is not
      only a fundamental theoretical limit for potential predictive power, but also an
      approachable target for actual prediction accuracy. 

PMID- 24113277
TI  - A qualitative participatory study to identify experiences of coronary heart
      disease patients to support the development of online self-management services.
AB  - OBJECTIVE: Web-based self-management services remain underutilized in current
      practice. Our aim was to gain insight into disease and self-management
      experiences of patients in early and progressive stages of coronary heart disease
      (CHD), to understand moderating effects of daily life experiences on the
      utilization of web-based self-management services and preconditions for use.
      METHODS: We applied generative research techniques, which stem from the field of
      product design and are characterized by the use of creative processes. Three
      groups of patients with CHD received a sensitizing package to document and
      reflect on their health, and were subsequently either interviewed or participated
      in a focus group session. RESULTS: In total, 23 patients participated in this
      study. Emerging themes were (1) fear for recurrent events, (2) experiences with
      professional care, (3) the perceived inability to prevent disease progression,
      (4) the desire to go on living without thinking about the disease every day, (5)
      the social environment as a barrier to or facilitator for self-management, and
      (6) the need for information tailored to personal preferences. CONCLUSION: How
      patients experience their disease varies between stable and post-acute stages, as
      well as between early and progressive stages of CHD. Patients in post-acute
      stages of the disease seem to be most amenable to support, while patients in
      stable stages want to live their life without being reminded of their disease. In
      the context of self-management, web-based services should be adapted to the
      variation in needs that occur in the different stages of CHD and new strategies
      to fit such services to these needs should be developed. Furthermore, they should
      be tailored to patients' individual health situation and preferences, support
      patient empowerment, and manage expectations regarding the progression of their
      disease.

PMID- 24113278
TI  - Population attributable risk of modifiable risk factors associated with invasive
      breast cancer in women aged 45-69 years in Queensland, Australia.
AB  - OBJECTIVES: To quantify the population attributable risk of key modifiable risk
      factors associated with breast cancer incidence in Queensland, Australia. STUDY
      DESIGN: Population attributable fractions (PAFs) for high body mass index (BMI),
      use of hormone replacement therapy (HRT), alcohol consumption and inadequate
      physical activity were calculated, using prevalence data from a representative
      survey of women attending mammographic screening at BreastScreen Queensland in
      2008 and relative risk estimates sourced from published literature. Attributable
      cancers were calculated using 'underlying' breast cancer incidence data for 2008
      based on Poisson regression models, adjusting for the inflation of incidence due
      to the effects of mammographic screening. MAIN OUTCOME MEASURES: Attributable
      burden of breast cancer due to high body mass index (BMI), use of hormone
      replacement therapy (HRT), alcohol consumption and inadequate physical activity.
      RESULTS: In Queensland women aged 45-69 years, an estimated 12.1% (95% CI: 11.6
      12.5%) of invasive breast cancers were attributable to high BMI in post
      menopausal women who have never used HRT; 2.8% (95% CI: 2.7-2.9%) to alcohol
      consumption; 7.6% (95% CI: 7.4-7.9%) to inadequate physical activity in post
      menopausal women and 6.2% (95% CI: 5.5-7.0%) to current use of HRT after
      stratification by BMI and type of HRT used. Combined, just over one quarter
      (26.0%; 95% CI: 25.4-26.6%) of all invasive breast cancers in Queensland women
      aged 45-69 years in 2008 were attributable to these modifiable risk factors.
      CONCLUSIONS: There is benefit in targeting prevention strategies to modify
      lifestyle behaviours around BMI, physical activity, HRT use and alcohol
      consumption, as a reduction in these risk factors could decrease invasive breast
      cancer incidence in the Queensland population.

PMID- 24113279
TI  - When viewing empathy-eliciting scenarios, incarcerated men with high psychopathy
      display differences in brain activity compared with those with low psychopathy.

PMID- 24113280
TI  - Novel behavior of monolayer quantum gases on graphene, graphane and
      fluorographene.
AB  - This article discusses the behavior of submonolayer quantum films (He and H2) on
      graphene and newly discovered surfaces that are derived from graphene. Among
      these substrates are graphane (abbreviated GH), which has an H atom bonded to
      each C atom, and fluorographene (GF). The subject is introduced by describing the
      related problem of monolayer films on graphite. For that case, extensive
      experimental and theoretical investigations have revealed that the phase diagrams
      of the Bose gases (4)He and para-H2 are qualitatively similar, differing
      primarily in a higher characteristic temperature scale for H2 than for He. The
      phase behavior of these films on one side of pristine graphene, or both sides of
      free-standing graphene, is expected to be similar to that on graphite. We point
      out the possibility of novel phenomena in adsorption on graphene related to the
      large flexibility of the graphene sheet, to the non-negligible interaction
      between atoms adsorbed on opposite sides of the sheet and to the perturbation
      effect of the adsorbed layer on the Dirac electrons. In contrast, the behavior
      predicted on GF and GH surfaces is very different from that on graphite, a result
      of the different corrugation, i.e., the lateral variation of the potential
      experienced by these gases. This arises because on GF, for example, half of the F
      atoms are located above the C plane while the other half are below this plane.
      Hence, the He and H2 gases experience very different potentials from those on
      graphite or graphene. As a result of this novel geometry and potential, distinct
      properties are observed. For example, the (4)He film's ground state on graphite
      is a two-dimensional (2D) crystal commensurate with the substrate, the famous
      [Formula: see text] phase; on GF and GH, instead, it is predicted to be an
      anisotropic superfluid. On GF the anisotropy is so extreme that the roton
      excitations are very anisotropic, as if the bosons are moving in a multiconnected
      space along the bonds of a honeycomb lattice. Such a novel phase has not been
      predicted or observed previously on any substrate. Also, in the case of (3)He the
      film's ground state is a fluid, thus offering the possibility of studying an
      anisotropic Fermi fluid with a tunable density. The exotic properties expected
      for these films are discussed along with proposed experimental tests.

PMID- 24113281
TI  - Sirtuin 7 plays a role in ribosome biogenesis and protein synthesis.
AB  - It has been shown that SIRT7 regulates rDNA transcription and that reduced SIRT7
      levels inhibit tumor growth. This anti-tumor effect could be due to reduced Pol I
      activity and perturbed ribosome biogenesis. In this study, using pulse labeling
      with RNA and amino acid analogs, we found that SIRT7 knockdown efficiently
      suppressed both RNA and protein synthesis. Surprisingly, SIRT7 knockdown
      preferentially inhibited protein synthesis over rDNA transcription, whereas the
      levels of both were reduced to similar extents following Pol I knockdown. Using
      an affinity purification mass spectrometry approach and functional analyses of
      the resulting SIRT7 interactome, we identified and validated SIRT7 interactions
      with proteins involved in ribosomal biogenesis. Indeed, SIRT7 co-fractionated
      with monoribosomes within a sucrose gradient. Using reciprocal isolations, we
      determined that SIRT7 interacts specifically with mTOR and GTF3C1, a component of
      the Pol III transcription factor TFIIIC2 complex. Further studies found that
      SIRT7 knockdown triggered an increase in the levels of LC3B-II, an autophagosome
      marker, suggesting a link between SIRT7 and the mTOR pathway. Additionally, we
      provide several lines of evidence that SIRT7 plays a role in modulating Pol III
      function. Immunoaffinity purification of SIRT7-GFP from a nuclear fraction
      demonstrated specific SIRT7 interaction with five out of six components of the
      TFIIIC2 complex, but not with the TFIIIA or TFIIIB complex, the former of which
      is required for Pol III-dependent transcription of tRNA genes. ChIP assays showed
      SIRT7 localization to the Pol III targeting genes, and SIRT7 knockdown triggered
      a reduction in tRNA levels. Taken together, these data suggest that SIRT7 may
      regulate Pol III transcription through mTOR and the TFIIIC2 complex. We propose
      that SIRT7 is involved in multiple pathways involved in ribosome biogenesis, and
      we hypothesize that its down-regulation may contribute to an antitumor effect,
      partly through the inhibition of protein synthesis. 

PMID- 24113283
TI  - Energy estimation and measurement in critically ill patients.
AB  - The estimation of caloric needs of critically ill patients is usually based on
      energy expenditure (EE), while current recommendations for caloric intake most
      often rely on a fixed amount of calories. In fact, during the early phase of
      critical illness, caloric needs are probably lower than EE, as a substantial
      proportion of EE is covered by the non-inhibitable endogenous glucose production.
      Hence, the risk of overfeeding is higher during the early phase than the late
      phase, while the risk of underfeeding is higher during the late phase of critical
      illness. Therefore, an accurate measurement of EE can be helpful to prevent early
      overfeeding and late underfeeding. Available techniques to assess EE include
      predictive equations, calorimetry, and doubly labeled water, the reference
      method. The available predictive equations are often inaccurate, while indirect
      calorimetry is difficult to perform for several reasons, including a shortage of
      reliable devices and technical limitations. In this review, the authors intend to
      discuss the different techniques and the influence of the method used on the
      interpretation of the results of clinical studies. 

PMID- 24113282
TI  - A human proteome microarray identifies that the heterogeneous nuclear
      ribonucleoprotein K (hnRNP K) recognizes the 5' terminal sequence of the
      hepatitis C virus RNA.
AB  - Stem-loop I (SL1) located in the 5' untranslated region of the hepatitis C virus
      (HCV) genome initiates binding to miR-122, a microRNA required for hepatitis HCV
      replication. However, proteins that bind SL1 remain elusive. In this study, we
      employed a human proteome microarray, comprised of ~17,000 individually purified
      human proteins in full-length, and identified 313 proteins that recognize HCV
      SL1. Eighty-three of the identified proteins were annotated as liver-expressing
      proteins, and twelve of which were known to be associated with hepatitis virus.
      siRNA-induced silencing of eight out of 12 candidate genes led to at least 25%
      decrease in HCV replication efficiency. In particular, knockdown of heterogeneous
      nuclear ribonucleoprotein K (hnRNP K) reduced HCV replication in a concentration
      dependent manner. Ultra-violet-crosslinking assay also showed that hnRNP K, which
      functions in pre-mRNA processing and transport, showed the strongest binding to
      the HCV SL1. We observed that hnRNP K, a nuclear protein, is relocated in the
      cytoplasm in HCV-expressing cells. Immunoprecipitation of the hnRNP K from Huh7.5
      cells stably expressing HCV replicon resulted in the co-immunoprecipitation of
      SL1. This work identifies a cellular protein that could have an important role in
      the regulation of HCV RNA gene expression and metabolism. 

PMID- 24113285
TI  - An Amplex Red-based fluorometric and spectrophotometric assay for L-asparaginase
      using its natural substrate.
AB  - We report on the development of a sensitive real-time assay for monitoring the
      activity of L-asparaginase that hydrolyzes L-asparagine to L-aspartate and
      ammonia. In this method, L-aspartate is oxidized by L-aspartate oxidase to
      iminoaspartate and hydrogen peroxide (H2O2), and in the detection step
      horseradish peroxidase uses H2O2 to convert the colorless, nonfluorescent reagent
      Amplex Red to the red-colored and highly fluorescent product resorufin. The assay
      was validated in both the absorbance and the fluorescence modes. We show that,
      due to its high sensitivity and substrate selectivity, this assay can be used to
      measure enzymatic activity in human serum containing L-asparaginase.

PMID- 24113284
TI  - Essential role of conformational selection in ligand binding.
AB  - Two competing and mutually exclusive mechanisms of ligand recognition -
      conformational selection and induced fit - have dominated our interpretation of
      ligand binding in biological macromolecules for almost six decades.
      Conformational selection posits the pre-existence of multiple conformations of
      the macromolecule from which the ligand selects the optimal one. Induced fit, on
      the other hand, postulates the existence of conformational rearrangements of the
      original conformation into an optimal one that are induced by binding of the
      ligand. In the former case, conformational transitions precede the binding event;
      in the latter, conformational changes follow the binding step. Kineticists have
      used a facile criterion to distinguish between the two mechanisms based on the
      dependence of the rate of relaxation to equilibrium, kobs, on the ligand
      concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been
      seen as diagnostic of conformational selection, while a value of kobs increasing
      hyperbolically with [L] has been considered diagnostic of induced fit. However,
      this simple conclusion is only valid under the rather unrealistic assumption of
      conformational transitions being much slower than binding and dissociation
      events. In general, induced fit only produces values of kobs that increase with
      [L] but conformational selection is more versatile and is associated with values
      of kobs that increase with, decrease with or are independent of [L]. The richer
      repertoire of kinetic properties of conformational selection applies to kinetic
      mechanisms with single or multiple saturable relaxations and explains the
      behavior of nearly all experimental systems reported in the literature thus far.
      Conformational selection is always sufficient and often necessary to account for
      the relaxation kinetics of ligand binding to a biological macromolecule and is
      therefore an essential component of any binding mechanism. On the other hand,
      induced fit is never necessary and only sufficient in a few cases. Therefore, the
      long assumed importance and preponderance of induced fit as a mechanism of ligand
      binding should be reconsidered. 

PMID- 24113286
TI  - Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical
      technology.
AB  - In this work the use of a high-throughput nanomechanical detection system based
      on a DVD-ROM optical drive and cantilever sensors is presented for the detection
      of urokinase plasminogen activator receptor inflammatory biomarker (uPAR).
      Several large scale studies have linked elevated levels of soluble uPAR (suPAR)
      to infectious diseases, such as HIV, and certain types of cancer. Using hundreds
      of cantilevers and a DVD-based platform, cantilever deflection response from
      antibody-antigen recognition is investigated as a function of suPAR
      concentration. The goal is to provide a cheap and portable detection platform
      which can carry valuable prognostic information. In order to optimize the
      cantilever response the antibody immobilization and unspecific binding are
      initially characterized using quartz crystal microbalance technology. Also, the
      choice of antibody is explored in order to generate the largest surface stress on
      the cantilevers, thus increasing the signal. Using optimized experimental
      conditions the lowest detectable suPAR concentration is currently around 5 nM.
      The results reveal promising research strategies for the implementation of
      specific biochemical assays in a portable and high-throughput microsensor-based
      detection platform. 

PMID- 24113287
TI  - Screening of the chemical reactivity of three different graphite sources using
      the formation of reductively alkylated graphene as a model reaction.
AB  - Reductive alkylation of three graphite starting materials G(flake), G(powder),
      and G(spherical) reveals pronounced differences in the obtained covalently
      functionalized graphene with respect to the degree of functionalization,
      exfoliation efficiency and product homogeneity, as demonstrated by statistical
      Raman microscopy (SRM), TGA/MS, IR-spectroscopy and solubility behavior. 

PMID- 24113289
TI  - Identifying major depressive disorder using Hurst exponent of resting-state brain
      networks.
AB  - Resting-state functional magnetic resonance imaging (fMRI) studies of major
      depressive disorder (MDD) have revealed abnormalities of functional connectivity
      within or among the resting-state networks. They provide valuable insight into
      the pathological mechanisms of depression. However, few reports were involved in
      the "long-term memory" of fMRI signals. This study was to investigate the "long
      term memory" of resting-state networks by calculating their Hurst exponents for
      identifying depressed patients from healthy controls. Resting-state networks were
      extracted from fMRI data of 20 MDD and 20 matched healthy control subjects. The
      Hurst exponent of each network was estimated by Range Scale analysis for further
      discriminant analysis. 95% of depressed patients and 85% of healthy controls were
      correctly classified by Support Vector Machine with an accuracy of 90%. The right
      fronto-parietal and default mode network constructed a deficit network (lower
      memory and more irregularity in MDD), while the left fronto-parietal,
      ventromedial prefrontal and salience network belonged to an excess network
      (longer memory in MDD), suggesting these dysfunctional networks may be related to
      a portion of the complex of emotional and cognitive disturbances. The abnormal
      "long-term memory" of resting-state networks associated with depression may
      provide a new possibility towards the exploration of the pathophysiological
      mechanisms of MDD. 

PMID- 24113288
TI  - Activation of an innate immune response in the schistosome-transmitting snail
      Biomphalaria glabrata by specific bacterial PAMPs.
AB  - Injection of crude lipopolysaccharide (LPS) from Escherichia coli into the
      hemocoel of Biomphalaria glabrata stimulates cell proliferation in the amebocyte
      producing organ (APO). However, it is not known if mitogenic activity resides in
      the lipid A or O-polysaccharide component of LPS. Moreover, the possible role of
      substances that commonly contaminate crude LPS and that are known to stimulate
      innate immune responses in mammals, e.g., peptidoglycan (PGN), protein, or
      bacterial DNA, is unclear. Therefore, we tested the effects of the following
      injected substances on the snail APO: crude LPS, ultrapurified LPS (lacking
      lipoprotein contamination), two forms of lipid A, (diphosphoryl lipid A and Kdo2
      lipid A), O-polysaccharide, Gram negative PGN, both crude and ultrapurified (with
      and without endotoxin activity, respectively), Gram positive PGN, PGN components
      Tri-DAP and muramyl dipeptide, and bacterial DNA. Whereas crude LPS,
      ultrapurified LPS, and crude PGN were mitogenic, ultrapurified PGN was not.
      Moreover, LPS components, PGN components, and bacterial DNA were inactive. These
      results suggest that it is the intact LPS molecule which stimulates cell division
      in the APO.

PMID- 24113290
TI  - Test-retest reliability of the ABILHAND questionnaire in persons with chronic
      stroke.
AB  - BACKGROUND: Reliable and valid outcome measures are needed to be able to evaluate
      recovery, effects of rehabilitation interventions, and changes over time. The
      ABILHAND Questionnaire is a measure of a patient's self-reported ability to
      perform complex daily activities involving use of the hand. This instrument is
      commonly used in stroke rehabilitation settings, but data about the measurement
      variability are missing. OBJECTIVE: To assess the test-retest reliability of the
      ABILHAND Questionnaire in persons with chronic stroke and to define limits for
      the smallest change that indicates a real change, both for a group of individuals
      and for a single individual. DESIGN: A test-retest reliability study. SETTINGS:
      University hospital. PARTICIPANTS: A convenience sample of 43 persons (11 women
      and 32 men; mean age 64 years) with mild to moderate impairments of hand function
      6-48 months after sustaining a stroke. INTERVENTION: Not applicable. MAIN OUTCOME
      MEASUREMENTS: The ABILHAND Questionnaire is Rasch analyzed, enabling ordinal data
      to be converted into an interval scale (logits) and the use of parametric
      statistical analyses. The participants responded to 23 items in the ABILHAND
      Questionnaire on 2 occasions, 2 weeks apart. Reliability was assessed with the
      intraclass correlation coefficient (ICC22.1), the mean difference between the
      test sessions (d) together with the 95% confidence intervals for d, the standard
      error of measurement (SEM and SEM%), the smallest real difference (SRD and SRD%),
      and a Bland and Altman graph. RESULTS: Four outliers with high mean logit scores
      (>4.0) were identified in the sample. The results therefore are presented both
      for the entire sample (n = 43) and without the 4 outliers (n = 39). The test
      retest agreement was high: ICC2,1 = 0.85 (n = 43) and 0.91 (n = 39). The SEM%,
      which represents the smallest change that indicates a real improvement for a
      group of individuals, was 21% (n = 43) and 15% (n = 39). The SRD%, which
      represents the smallest change that indicates a real clinical improvement for a
      single individual, was 59% (n = 43) and 42% (n = 39), respectively. CONCLUSION:
      The ABILHAND Questionnaire is reliable in persons with chronic stroke and can be
      recommended to evaluate recovery, rehabilitation interventions, and changes over
      time in a group of individuals but is less suitable for a single individual.

PMID- 24113291
TI  - Correlative multimodal probing of ionically-mediated electromechanical phenomena
      in simple oxides.
AB  - The local interplay between the ionic and electronic transport in NiO is explored
      using correlative imaging by first-order reversal curve measurements in current
      voltage and electrochemical strain microscopy. Electronic current and
      electromechanical response are observed in reversible and electroforming regime.
      These studies provide insight into local mechanisms of electroresistive phenomena
      in NiO and establish universal method to study interplay between the ionic and
      electronic transport and electrochemical transformations in mixed electronic
      ionic conductors. 

PMID- 24113292
TI  - A pore scale investigation of crude oil distribution and removal from homogeneous
      porous media during surfactant-induced remediation.
AB  - A pore-scale study was conducted to understand interfacial processes contributing
      to the removal of crude oils from a homogeneous porous medium during surfactant
      induced remediation. Synchrotron X-ray microtomography (SXM) was used to obtain
      high-resolution three-dimensional images of the two-fluid-phase oil/water system,
      and quantify temporal changes in oil blob distribution, blob morphology, and blob
      surface area before and after sequential surfactant flooding events. The
      reduction of interfacial tension in conjunction with the sufficient increase in
      viscous forces as a result of surfactant flushing was most likely responsible for
      mobilization and recovery of the two lighter oil fractions. However,
      corresponding increases in viscous forces as a result of a reduction of
      interfacial tension were insufficient to initiate and maintain the displacement
      (recovery) of the heavy crude oil fraction during surfactant flushing. In
      contrast to the heavy oil system, changes in trapping number for the lighter
      fraction crude oils were sufficient to initiate mobilization as a result of
      surfactant flushing. Both light and medium oil fractions showed an increase in
      the number of blobs and total blob surface area, and a reduction in the total
      volume after 2 pore volumes (PVs) of surfactant flooding. This increase in
      surface area was attributed to the change in blob morphology from spherical to
      more complex non-spherical ganglia shape characteristics. Moreover, the increase
      in the number of oil blobs from larger to smaller particles after surfactant
      flushing may have contributed to the greater cumulative oil surface area.
      Complete recovery of light and medium oil fractions resulted after 5 PVs of
      surfactant flooding, whereas the displacement efficiency of heavy-oil fraction
      was severely limited, even after extended periods of flushing. The results of
      these experiments demonstrate the utility of SXM for quantifying pore-scale
      interfacial characteristics for specific crude-oil-fraction/porous-medium
      systems, critical for understanding mobilization/removal relationships in which
      surfactant-enhanced remediation techniques will be most successful. 

PMID- 24113293
TI  - Preterm prelabor rupture of membranes (PPROM) is not associated with presence of
      viral genomes in the amniotic fluid.
AB  - BACKGROUND: The role of viral infections in preterm prelabor rupture of the
      membranes (PPROM) is not established. Studies on the presence of viral genomes in
      the amniotic fluid (AF) collected in pregnancies complicated by PPROM show
      contradictory outcomes. OBJECTIVES: To investigate AF samples of PPROM
      pregnancies for the presence of viral genomes. STUDY DESIGN: AF samples from
      patients with PPROM were collected during a 4-year (2008-2012) observational
      study. 174 women were included with selection criteria of singleton pregnancy,
      PPROM, and maternal age of 18 years and above. PCR was used for detection of
      human cytomegalovirus (HCMV), herpes simplex virus (HSV), parvovirus B19, human
      adenoviruses (HAdV), enteroviruses (EV) and human parechovirus (HPeV). The
      selection of these viral targets was based on literature regarding screening of
      AF for presence of viral genomes. RESULTS: Only a single sample was positive out
      of the 174 tested AFs, HCMV DNA was detected. CONCLUSIONS: PPROM is not
      associated with active viral infections.

PMID- 24113294
TI  - Evaluation of the Bio-Rad Multispot HIV-1/HIV-2 Rapid Test as an alternative to
      Western blot for confirmation of HIV infection.
AB  - BACKGROUND: In the United States, a new HIV diagnostic algorithm has been
      proposed that uses an HIV-1/HIV-2 antibody differentiation immunoassay instead of
      Western blot or immunofluoresence for confirmatory testing. OBJECTIVES: To
      evaluate the Multispot HIV-1/HIV-2 Rapid Test (Multispot) as an alternative to
      Western blot analysis for confirmation of HIV infection. STUDY DESIGN: A series
      of 205 serum and plasma specimens positive for HIV-1 or HIV-2 were used to
      compare the performance of Multispot to a standard HIV-1 Western blot. Positive
      samples included 63 specimens from patients>18 months of age, 33 proficiency
      survey specimens, and 109 specimens from nine commercial seroconversion and
      performance panels. In addition, 63 specimens from 51 HIV-exposed, uninfected
      children<=18 months of age in various stages of seroreversion and 192 HIV
      negative samples were tested. Specimens were initially screened using a 4th
      generation HIV Ag/Ab Combo assay. RESULTS: Multispot readily discriminated
      between individuals with HIV-1 or HIV-2 infection and those who were uninfected.
      Of the 205 samples repeatedly reactive by the 4th generation screening assay,
      infection status was correctly confirmed by Multispot in 83.9% (172/205) compared
      to 68.8% (141/205) for Western blot. Multispot detected HIV-1 earlier in 27.6% of
      low-titer antibody specimens called indeterminate by Western blot, and
      effectively reduced the number of indeterminate results in seroreverting HIV-1
      exposed, uninfected infants and for HIV-2 infections misinterpreted as
      indeterminate or positive by HIV-1 Western blot. CONCLUSIONS: Multispot offers
      speed and simplicity over Western blot and has an excellent performance for
      differentiation and confirmation of antibodies to HIV-1 and HIV-2.

PMID- 24113295
TI  - Lithium incorporation at the MoS2/graphene interface: an ab initio investigation.
AB  - Based on ab initio calculations, we examine the incorporation of Li atoms in the
      MoS2/graphene interface. We find that the intercalated Li atoms are energetically
      more stable than Li atoms adsorbed on the MoS2 surface. The intercalated atoms
      interact with both graphene sheet and MoS2 layer, increasing the Li binding
      energies. However, the equilibrium geometries are ruled by the MoS2 layer, where
      the intercalated Li atoms lie on the top (LiT) and hollow (LiH) sites of the MoS2
      layer. We calculate the Li diffusion barriers, along the LiT -> LiH diffusion
      path, where we find similar energy barriers compared with that obtained for Li
      adatoms on the MoS2 surface. Our results allow us to infer that the Li storage
      capacity increases at MoS2/G interfaces, in comparison with Li adatoms on the
      MoS2 surface-however, with no reduction on the mobility of the intercalated Li
      atoms. Those properties are interesting/useful to the development of Li batteries
      based on MoS2.

PMID- 24113296
TI  - Osteodistraction of mandibles with a small bone defect at the planned osteotomy
      site: a histological pilot study in dogs.
AB  - AIM: To develop a treatment plan for cases in which a bone defect is located on
      the osteotomy line of mandibular osteodistraction (DO). SUBJECTS AND METHODS:
      Bilateral DO was performed in 17 Mongrel dogs. Prior to surgery, the 34 hemi
      mandibles were randomly allocated to three groups: C (n = 10; a standard DO was
      performed), D - G (n = 12; a bone defect was created on the DO osteotomy line),
      and D + G (n = 12; the bone defect on the osteotomy line was grafted). After one
      week of latency, 8 days of distraction, and 4 weeks of consolidation the animals
      were sacrificed, and the newly formed bone were examined. RESULTS: In group C,
      two zones of immature trabecular bone originating from host bone margins were
      separated by a central fibrous zone. In group D + G uniform new bone formation of
      the entire distraction gap was observed. In group D - G the distraction gap was
      mainly filled with fibrous tissue. The values for the newly formed bone volume
      and trabecular thickness were not significantly different between groups D + G
      and C, but were higher than values in group D - G (p < 0.05). CONCLUSION: When a
      mandibular defect is located at the site of distraction osteotomy, DO can be
      performed simultaneous with bone grafting of the defect.

PMID- 24113298
TI  - Cement lines and interlamellar areas in compact bone as strain amplifiers -
      contributors to elasticity, fracture toughness and mechanotransduction.
AB  - Bone is multi-scale hierarchical composite material making the prediction of
      fragility, as well as pinning it to a certain cause, complicated. For proper
      mechanical simulation and reflection of bone properties in models, microscopic
      structural features of bone tissue need to be included. This study sets out to
      gain a mechanistic insight into the role of various microstructural features of
      bone tissue in particular cement lines and interlamellar areas. Further the
      hypothesis that compliant interlamellar areas and cement lines within osteonal
      bone act as strain amplifiers was explored. To this end, a series of
      experimentally-based micromechanical finite element models of bovine osteonal
      bone were developed. Different levels of detail for the bone microstructure were
      considered and combined with the results of physical three-point bending tests
      and an analytical composite model of a single osteon. The objective was to
      examine local and global effects of interface structures. The geometrical and
      microstructural characteristics of the bone samples were derived from microscopy
      imaging. Parametric finite element studies were conducted to determine optimal
      values of the elastic modulus of interstitial bone and interlamellar areas. The
      average isotropic elastic modulus of interfaces suggested in this study is
      88.5MPa. Based on the modelling results, it is shown that interfaces are areas of
      accumulated strain in bone and are likely to act as potential paths for crack
      propagation. The strain amplification capability of interface structures in the
      order of 10 predicted by the models suggests a new explanation for the levels of
      strain required in bone homoeostasis for maintenance and adaptation. 

PMID- 24113297
TI  - Effects of different post-spin stretching conditions on the mechanical properties
      of synthetic spider silk fibers.
AB  - Spider silk is a biomaterial with impressive mechanical properties, resulting in
      various potential applications. Recent research has focused on producing
      synthetic spider silk fibers with the same mechanical properties as the native
      fibers. For this study, three proteins based on the Argiope aurantia Major
      ampullate Spidroin 2 consensus repeat sequence were expressed, purified and spun
      into fibers. A number of post-spin draw conditions were tested to determine the
      effect of each condition on the mechanical properties of the fiber. In all cases,
      post-spin stretching improved the mechanical properties of the fibers. Aqueous
      isopropanol was the most effective solution for increasing extensibility, while
      other solutions worked best for each fiber type for increasing tensile strength.
      The strain values of the stretched fibers correlated with the length of the
      proline-rich protein sequence. Structural analysis, including X-ray diffraction
      and Raman spectroscopy, showed surprisingly little change in the initial as-spun
      fibers compared with the post-spin stretched fibers. 

PMID- 24113299
TI  - Simulative and experimental investigation on the cleavage site that generates the
      soluble human LOX-1.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger
      receptor that mediates the recognition, the binding and internalization of ox
      LDL. A truncated soluble form of LOX-1 (sLOX-1) has been identified that, at
      elevated levels, has been associated to acute coronary syndrome. Human sLOX-1 is
      the extracellular part of membrane LOX-1 which is cleaved in the NECK domain with
      a mechanism that has not yet been identified. Purification of human sLOX-1 has
      been carried out to experimentally identify the cleavage site region within the
      NECK domain. Molecular modelling and classical molecular dynamics simulation
      techniques have been used to characterize the structural and dynamical properties
      of the LOX-1 NECK domain in the presence and absence of the CTLD recognition
      region, taking into account the obtained proteolysis results. The simulative data
      indicate that the NECK domain is stabilized by the coiled-coil heptad repeat
      motif along the simulations, shows a definite flexibility pattern and is
      characterized by specific electrostatic potentials. The detection of a mobile
      inter-helix space suggests an explanation for the in vivo susceptibility of the
      NECK domain to the proteolytic cleavage, validating the assumption that the NECK
      domain sequence is composed of a coiled-coil motif destabilized in specific
      regions of functional significance.

PMID- 24113300
TI  - Histological changes of high axial myopia.
AB  - To describe pathological changes in the anatomy of highly myopic (axially
      elongated) eyes, enucleated globes were examined by light microscopy and ocular
      structures were measured histomorphometrically. These studies revealed that
      highly axially myopic eyes show continuous thinning of the sclera starting at or
      behind the equator with a maximal thinning at the posterior pole; a profound
      thinning of the choroid decreasing from ~ 250 to <10 MUm in extreme axial myopia,
      secondary macular defects in the Bruch's membrane associated with a complete loss
      of retinal pigment epithelium and choriocapillaris, and retinal photoreceptors; a
      Bruch's membrane of normal thickness in contrast to the profound thinning of the
      choroid and the sclera; an up to 10-fold elongation and thinning of the
      peripapillary scleral flange as anterior roof of the orbital cerebrospinal fluid
      space, and subsequently a retrobulbar extension of the cerebrospinal fluid space;
      an increased distance of the peripapillary arterial circle of Zinn-Haller to the
      optic disc border; an elongation and thinning of the lamina cribrosa with a
      subsequently decreased distance between the intraocular pressure compartment and
      the retrobulbar orbital cerebrospinal fluid pressure compartment; an increasing
      exposure of the peripheral posterior lamina cribrosa surface to the cerebrospinal
      fluid space, no longer buffered by the solid optic nerve tissue; and the
      development and enlargement of parapapillary gamma zone, in contrast to a myopia
      independent parapapillary beta zone. These anatomical changes may be associated
      with high axial myopia-related complications such as an increased susceptibility
      of glaucomatous optic neuropathy and myopic retinopathy.

PMID- 24113301
TI  - Analyses of shape of eyes and structure of optic nerves in eyes with tilted disc
      syndrome by swept-source optical coherence tomography and three-dimensional
      magnetic resonance imaging.
AB  - PURPOSE: To evaluate the deeper structures of the optic nerve and to analyze the
      shape of eyes with tilted disc syndrome (TDS) by swept-source optical coherence
      tomography (OCT) and three-dimensional magnetic resonance imaging (3D MRI).
      METHODS: The medical records of 54 eyes of 36 patients with TDS were reviewed.
      The patients with TDS and high myopia were analyzed separately from those without
      high myopia. All the eyes were examined with a swept-source OCT, and 22 of the
      eyes were examined by 3D MRI. RESULTS: A total of 38 eyes of 29 patients were
      highly myopic and 16 eyes of 15 patients were not highly myopic. The
      representative OCT findings of the optic disc were: a sloping of the lamina
      cribrosa posteriorly from the upper part to the lower part, a protrusion of the
      upper edge of Bruch's membrane, and choroid. The distance and the depth of the
      most protruded point from the fovea were significantly greater in the eyes with
      non-highly myopic TDS than those with highly myopic TDS. In the 3D MRI, the lower
      part of the posterior segment was protruded outward, and the optic nerves
      attached at the upper nasal edge of the protrusion. CONCLUSIONS: The
      abnormalities detected by swept-source OCT and 3D MRI analyses indicate the
      possibility that the essential pathology of TDS is a deformity of the inferior
      globe below the optic nerve, and the positional relation between the fovea and
      the inferior protrusion determines the degree of myopia.

PMID- 24113302
TI  - Response to Fajgenbaum.

PMID- 24113304
TI  - Is the mechanism of 'poppers maculopathy' photic injury?

PMID- 24113303
TI  - Ophthalmic manifestations in a Chinese family with familial amyloid
      polyneuropathy due to a TTR Gly83Arg mutation.
AB  - PURPOSE: To describe the characteristic ophthalmic phenotypes of a large Chinese
      family with familial amyloid polyneuropathy due to a missense mutation in
      transthyretin (TTR) (c.307 C>G). METHODS: Twenty-seven individuals (12 affected,
      15 unaffected) from a five-generation Chinese family underwent general medical
      examination and comprehensive ophthalmic examination, including best correct
      visual acuity, intraocular pressure measurements, Schirmer test, slitlamp
      examination, fundoscopy, and ocular ultrasonography. Histological examination of
      vitreous biopsies using Congo red staining and immunohistochemistry was
      performed. Cardiovascular magnetic resonance (CMR), electrocardiogram, and
      echocardiogram were used to evaluate cardiac amyloidosis. Electromyography was
      used to evaluate nerve function. All four exons of TTR were amplified by PCR,
      sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an
      ABI 3700XL Genetic Analyzer. RESULTS: All 12 affected individuals in the family
      had ocular manifestations, including severe vitreous opacities, secondary
      glaucoma, xerophthalmia, dyscoria, and attenuated retinal arteries. Congo red
      staining demonstrated amyloid deposits in the vitreous, and immunohistochemical
      staining confirmed the deposition of TTR proteins in the vitreous. Twelve
      individuals had polyneuropathy, and electromyography detected functional damage
      in peripheral nerves. One individual was diagnosed with cardiac amyloidosis by
      CMR. Direct sequencing revealed the heterozygous missense mutation in TTR (c.307
      C>G p.Gly83Arg) in all 12 affected individuals. The mutation co-segregated with
      the disease phenotype and was absent in 100 normal controls. CONCLUSIONS:
      Vitreous opacity is very common in patients with the TTR Gly83Arg mutation; other
      clinical characteristics associated with the mutation include polyneuropathy and
      cardiac amyloidosis.

PMID- 24113306
TI  - Acute effects of diesel exhaust particles and cisplatin on oxidative stress in
      cultured human kidney (HEK 293) cells, and the influence of curcumin thereon.
AB  - Particulate air pollution with particle diameters less than 2.5MUm contribute to
      respiratory and extra-respiratory morbidity and mortality. We have recently
      reported the first in vivo experimental evidence that Diesel exhaust particles
      (DEP) in the lung aggravated the renal, pulmonary, and systemic effects of
      cisplatin (CP)-induced acute renal failure in rats. This in vitro study sought to
      determine whether and to what extent does DEP exposure exacerbate the effects of
      CP-induced oxidative stress in human embryonic kidney (HEK-293) cells, and to
      examine if these effects could be mitigated/prevented with curcumin (the yellow
      pigment isolated from turmeric). Cells viability, cysteine uptake and oxidative
      stress indices [glutathione (GSH), total antioxidant capacity (TAC), and the
      activities of antioxidant enzymes (catalase; glutathione peroxidase; superoxide
      dismutase)] were evaluated in all study groups. DEP aggravated the CP- induced
      HEK-293 cells toxicity, as evidenced by decreasing cell viability and by inducing
      oxidative stress (GSH depletion, TAC impairment, and antioxidant enzymes
      inhibition). DEP, but not CP, significantly reduced cysteine uptake. Curcumin
      prevented the observed DEP and CP-induced cellular insults. These findings
      suggest that DEP augmented the CP-induced toxicity in HEK-293 cells. Curcumin
      exhibited a strong potential for protection against DEP and CP-induced
      cytotoxicity. 

PMID- 24113307
TI  - Translocation-associated salivary gland tumors: a review and update.
AB  - In recent years the discovery of translocations and the fusion oncogenes that
      they result in has changed the way diagnoses are made in the salivary gland.
      These genetic aberrations are recurrent and reproducible and at the very least
      serve as powerful diagnostic tools in salivary gland diagnosis and salivary gland
      classification. They also show promise as prognostic markers and hopefully as
      targets of therapy. Many of these fusions have been found in other tumor types
      that show little to no overlap with their salivary gland counterparts, but
      effectively they are specific within the salivary gland. In this review the 5
      tumors currently known to harbor translocations will be discussed, namely
      pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, mammary
      analog secretory carcinoma, and hyalinizing clear cell carcinoma. The discovery
      and implications of each fusion will be highlighted and how they have helped
      reshape the current classification of salivary gland tumors. 

PMID- 24113308
TI  - Identifying Lynch syndrome in patients with ovarian carcinoma: the significance
      of tumor subtype.
AB  - Up to 15% of ovarian cancers are etiologically linked with hereditary
      susceptibility. Within this group, germline mutations in mismatch repair (MMR)
      genes, known otherwise as Lynch syndrome (LS), account for the majority of cases
      that are not associated with mutations in BRCA1 or BRCA2. Clinical schemas
      specific for gynecologic cancers have been developed to identify patients with
      LS; however, many of the recommendations are poorly defined. Few case series of
      germline-confirmed LS-associated ovarian cancers have been reported, limited by
      small sample size and often lacking central pathology review. Much insight has
      been gained from studies of unselected cohorts, using immunohistochemical
      assessment of MMR protein expression or microsatellite instability analysis. In
      spite of contradictory results, likely reflective of differences in study design,
      sample size and methodology, a recurring observation is the overrepresentation of
      "endometriosis-associated tumors," namely, endometrioid and clear cell subtypes,
      in the group of ovarian tumors with MMR deficiency. In this review, we summarize
      the clinical and histomorphologic features of LS-associated/MMR-deficient ovarian
      epithelial cancers and recommend that reflex testing be performed on the basis of
      tumor subtype. 

PMID- 24113309
TI  - Classification of rhabdomyosarcoma and its molecular basis.
AB  - Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, has
      traditionally been classified into embryonal rhabdomyosarcoma (ERMS) and alveolar
      rhabdomyosarcoma (ARMS) for pediatric oncology practice. This review outlines the
      historical development of classification of childhood RMS and the challenges that
      have been associated with it, particularly problems with the diagnosis of "solid
      variant" ARMS and its distinction from ERMS. In addition to differences in
      clinical presentation and outcome, a number of genetic features underpin
      separation of ERMS from ARMS. Genetic differences associated with RMS
      subclassification include the presence of reciprocal translocations and their
      associated fusions in ARMS, amplification of genes in ARMS and its fusion
      subsets, chromosomal losses and gains that mostly occur in ERMS, and allelic
      losses and mutations usually associated with ERMS. Chimeric proteins encoded in
      most ARMS from the fusion of PAX3 or PAX7 with FOXO1 are expressed, result in a
      distinct pattern of downstream protein expression, and appear to be the proximate
      cause of the bad outcome associated with this subtype. A sizeable minority of
      ARMS lacks these fusions and shares the clinical and biological features of ERMS.
      A battery of immunohistochemical tests may prove useful in separating ERMS from
      ARMS and fusion-positive ARMS from fusion-negative ARMS. Because of limitation of
      predicting outcome solely based on histologic classification, treatment protocols
      will begin to utilize fusion testing for stratification of affected patients into
      low-risk, intermediate-risk, and high-risk groups. 

PMID- 24113310
TI  - GI tract tumors with melanocytic differentiation.
AB  - Gastrointestinal (GI) tract tumors with melanocytic differentiation may present
      significant diagnostic challenges both for the pathologist and the clinician.
      This comprehensive review discusses the relatively common as well as rare
      entities that have melanocytic differentiation in the GI tract. Clinical,
      histologic, immunohistochemical and molecular features are discussed along with
      prognosis and differential diagnosis. 

PMID- 24113311
TI  - Radiation-induced vascular lesions of the skin: an overview.
AB  - Radiation-induced cutaneous vascular neoplasms occur infrequently and comprise
      benign, so-called atypical vascular lesions (AVL) and angiosarcomas (AS), often
      being high-grade malignant tumors. Both arise most frequently within previously
      irradiated skin in breast-conserving-treated mammary cancer patients. Because of
      the different clinical course and, consequently, different therapeutic
      approaches, histopathologic distinction of AVL and AS is essential but
      significant morphologic overlap has been documented. Furthermore, the coexistence
      of these lesions or progression of AVL into AS has rarely been reported. Whether
      AVL is a precursor of AS is much debated and unresolved to date. Recent interest
      has focused on genetic changes and their differences in AS and AVL. MYC
      amplification and expression of the corresponding protein has been identified in
      AS in comparison with AVL. Therefore, MYC fluorescent in situ hybridization and
      anti-MYC immunohistochemical analysis are diagnostically useful in difficult
      cases. Furthermore, advanced tailored treatment strategies in AS, one of the most
      aggressive type of sarcoma, rely on identifying genes and proteins involved in
      malignant angiogenesis. 

PMID- 24113312
TI  - Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic
      entity!
AB  - Proliferative verrucous leukoplakia (PVL) is a rare less recognized form of oral
      leukoplakia. Patients with this condition represent a unique clinically and
      pathologically progressive characteristic from conventional leukoplakia. Because
      of the lack of defined pathologic lesions, identifying patients with the early
      diagnosis of PVL is challenging. This is largely due to the overlapping clinical
      and pathologic early features with conventional multifocal leukoplakia with
      dysplasia. The diagnosis can only be achieved through the keen clinical
      observation of the temporal progression in individual patients to verrucous
      and/or conventional squamous carcinoma. We present a brief view of the
      clinicopathologic and biological characteristics of PVL and discuss diagnosis,
      differential diagnosis, and management. 

PMID- 24113313
TI  - Modern approaches to the treatment of amyloidosis: the critical importance of
      early detection in surgical pathology.
AB  - The amyloidoses comprise a group of disorders of diverse etiology, in which
      different proteins undergo abnormal folding, leading to their deposition in
      tissues and concomitant tissue toxicity. This process ultimately leads to tissue
      destruction, with organ failure and progressive disease. Recent progress in the
      treatment of the systemic amyloidoses has dramatically changed the outlook for
      affected patients and their families. From a relatively rare and esoteric
      disorder that was typically diagnosed only at autopsy, or was invariably fatal if
      diagnosed during life, it has now become a disease for which, with modern
      therapies, durable responses and long-term survival can be achieved. The clinical
      symptoms are largely nonspecific, and therefore misdiagnosis, or late diagnosis,
      have been major detriments in achieving better treatment outcomes. Despite
      advances in laboratory medicine, amyloidoses are still diagnosed on the basis of
      the pathologic detection of deposits in tissues. Thus, effective primary
      screening for these diseases requires the active engagement of the pathology
      community at large, while specialized laboratories and treatment centers can
      offer secondary consultation and assistance with further steps. This review
      provides an update on pathogenesis, the clinical and pathologic features, and
      treatments of various amyloidoses, as well as the current terminology,
      classification, and practical considerations that are relevant to the diagnosis. 

PMID- 24113314
TI  - A silicon-based electrochemical sensor for highly sensitive, specific, label-free
      and real-time DNA detection.
AB  - We herein present a new kind of silicon-based electrochemical sensor using a gold
      nanoparticles-decorated silicon wafer (AuNPs@Si) as a high-performance electrode,
      which is facilely prepared via in situ AuNPs growth on a silicon wafer.
      Particularly significantly, the resultant electrochemical sensor is efficacious
      for label-free DNA detection with high sensitivity due to the unique merits of
      the prepared silicon-based electrode. Typically, DNA at remarkably low
      concentrations (1-10 fM) could be readily detected without requiring additional
      signal-amplification procedures, which is better than or comparable to the lowest
      DNA concentration ever detected via well-studied signal-amplification-assisted
      electrochemical sensors. Moreover, the silicon-based sensor features high
      specificity, allowing unambiguous discrimination of single-based mismatches. We
      further show that real-time DNA assembly is readily monitored via recording the
      intensity changes of current signals due to the robust thermal stability of the
      silicon-based electrode. The unprecedented advantages of the silicon-based
      electrochemical sensor would offer new opportunities for myriad sensing
      applications.

PMID- 24113315
TI  - Reprint of 'The psychometric properties of the McCarron assessment of
      neuromuscular development as a longitudinal measure with Australian youth'.
AB  - The importance of considering age and sex differences in the assessment of motor
      performance has been largely overlooked. This study examines the psychometric
      properties of the US developed McCarron Assessment of Neuromuscular Development
      (MAND) using data from a longitudinal sample of 986 Australian youth at 10, 14
      and 17 years. A key finding was the sex and age interaction of the Neuromuscular
      Developmental Index (NDI) (F=121.46, p<.001). Males had a significantly lower
      mean NDI score at 10 years and the females had a lower score at 17 years. The
      factor structure differed from the US samples (McCarron, 1997) at each age and
      between males and females. The sex specific analyses showed that the underlying
      structure was more complex for younger females. Although the MAND remains a
      useful test of motor performance for Australian children, further consideration
      is warranted regarding sex differences, the relevance of the US based normative
      tables and factor structures.

PMID- 24113316
TI  - Thymoquinone inhibits microtubule polymerization by tubulin binding and causes
      mitotic arrest following apoptosis in A549 cells.
AB  - Microtubule-Targeting agents (MTA) are indispensable for cancer therapeutics. We
      here report thymoquinone (TQ) as a new MTA that already has been appreciated for
      its anticancer effects. TQ induced G2/M cell cycle arrest in human non-small lung
      epithelial cells (A549) and majority of arrested cells were in mitosis. TQ
      depolymerized the microtubule (MT) network and disrupted mitotic spindle
      organization of A549 cells. MT depolymerization by TQ was followed by apoptosis
      and subsequent loss in cell viability (IC50 value of ~10 MUM). Interestingly, TQ
      didn't affect the MT network of normal HUVEC cells at and below the IC50
      concentration for A549 cells. TQ also inhibited tubulin polymerization in cell
      free system with an IC50 of 27 MUM and bound to tubulin heterodimers at a single
      site with a dissociation constant of 1.19 MUM at 25  degrees C. Binding of TQ to
      tubulin quenched the tryptophan fluorescence of protein in a time-dependent
      manner. The TQ-tubulin binding kinetics was biphasic in nature and equilibrated
      in 30 min. TQ competed with colchicine for tubulin binding with a Ki of 1.9 MUM
      as determined by modified Dixon plot analysis, this suggests TQ may bind tubulin
      at or near the colchicine binding site and in silico modeling study supported
      that. Our results establish a novel antimitotic mechanism of TQ by its direct
      binding to tubulin-MT network in A549 cells.

PMID- 24113317
TI  - Studies on peroxynitrite-modified H1 histone: implications in systemic lupus
      erythematosus.
AB  - Peroxynitrite is a powerful nitrating and oxidizing molecule and capable of
      modifying proteins' structure. Hyper-nitration of tyrosine residues has been seen
      in various pathological states, including autoimmune disorders like systemic
      lupus erythematosus (SLE) and rheumatoid arthritis. SLE, a chronic autoimmune
      disease, is primarily characterized by increased levels of autoantibodies,
      predominantly against ds-DNA. However, the initial antigenic stimulus for the
      disease etiopathogenesis has remained elusive. Carbonyl and nitrotyrosine have
      been extensively used as a biomarker of oxidative and nitrosative stress. In this
      study, commercially available H1 histone was exposed to increasing concentrations
      of peroxynitrite for 30 min. The peroxynitrite-mediated structural changes in
      histone were studied by ultraviolet & fluorescence spectroscopy, CD, HPLC, 1
      anilinonaphthalene-8-sulfonic acid binding and polyacrylamide gel
      electrophoresis. Analysis of results revealed that carbonyl and nitrotyrosine
      contents were significantly increased in peroxynitrite-modified H1 compared to
      native H1. In experimental animal, peroxynitrite-modified H1 induced high titre
      antibodies as compared to native H1, and the immunogenicity was found to be
      directly proportional to nitrotyrosine content. Further, the induced antibodies
      showed specificity for the immunogen and appreciable cross-reactions with
      tyrosine rich nitrated proteins. Formation of high molecular weight immune
      complex with retarded mobility further supports the specificity of induced anti
      peroxynitrite-modified H1 antibodies for the immunogen. Binding of SLE anti-DNA
      autoantibodies with peroxynitrite-modified H1 was analyzed by direct binding and
      competition ELISA. The data show preferential binding of SLE autoantibodies to
      peroxynitrite-modified H1 as compared to native H1 histone and native DNA. The
      results point towards the possible role of peroxynitrite-modified H1 histone in
      SLE etiopathogenesis.

PMID- 24113318
TI  - Autism and EMF? Plausibility of a pathophysiological link part II.
AB  - Autism spectrum conditions (ASCs) are defined behaviorally, but they also involve
      multileveled disturbances of underlying biology that find striking parallels in
      the physiological impacts of electromagnetic frequency and radiofrequency
      radiation exposures (EMF/RFR). Part I (Vol 776) of this paper reviewed the
      critical contributions pathophysiology may make to the etiology, pathogenesis and
      ongoing generation of behaviors currently defined as being core features of ASCs.
      We reviewed pathophysiological damage to core cellular processes that are
      associated both with ASCs and with biological effects of EMF/RFR exposures that
      contribute to chronically disrupted homeostasis. Many studies of people with ASCs
      have identified oxidative stress and evidence of free radical damage, cellular
      stress proteins, and deficiencies of antioxidants such as glutathione. Elevated
      intracellular calcium in ASCs may be due to genetics or may be downstream of
      inflammation or environmental exposures. Cell membrane lipids may be peroxidized,
      mitochondria may be dysfunctional, and various kinds of immune system
      disturbances are common. Brain oxidative stress and inflammation as well as
      measures consistent with blood-brain barrier and brain perfusion compromise have
      been documented. Part II of this paper documents how behaviors in ASCs may emerge
      from alterations of electrophysiological oscillatory synchronization, how EMF/RFR
      could contribute to these by de-tuning the organism, and policy implications of
      these vulnerabilities. It details evidence for mitochondrial dysfunction, immune
      system dysregulation, neuroinflammation and brain blood flow alterations, altered
      electrophysiology, disruption of electromagnetic signaling, synchrony, and
      sensory processing, de-tuning of the brain and organism, with autistic behaviors
      as emergent properties emanating from this pathophysiology. Changes in brain and
      autonomic nervous system electrophysiological function and sensory processing
      predominate, seizures are common, and sleep disruption is close to universal. All
      of these phenomena also occur with EMF/RFR exposure that can add to system
      overload ('allostatic load') in ASCs by increasing risk, and can worsen
      challenging biological problems and symptoms; conversely, reducing exposure might
      ameliorate symptoms of ASCs by reducing obstruction of physiological repair.
      Various vital but vulnerable mechanisms such as calcium channels may be disrupted
      by environmental agents, various genes associated with autism or the interaction
      of both. With dramatic increases in reported ASCs that are coincident in time
      with the deployment of wireless technologies, we need aggressive investigation of
      potential ASC-EMF/RFR links. The evidence is sufficient to warrant new public
      exposure standards benchmarked to low-intensity (non-thermal) exposure levels now
      known to be biologically disruptive, and strong, interim precautionary practices
      are advocated. 

PMID- 24113319
TI  - A multicentre year-long randomised controlled trial of exercise training
      targeting physical functioning in men with prostate cancer previously treated
      with androgen suppression and radiation from TROG 03.04 RADAR.
AB  - BACKGROUND: Long-term prostate cancer (PCa) survivors are at increased risk for
      comorbidities and physical deconditioning. OBJECTIVE: To determine the
      effectiveness of a year-long randomised controlled trial of exercise training in
      PCa survivors >5 yr postdiagnosis on physical functioning. DESIGN, SETTING, AND
      PARTICIPANTS: Between 2010 and 2011, 100 long-term PCa survivors from Trans
      Tasman Radiation Oncology Group 03.04 Randomised Androgen Deprivation and
      Radiotherapy previously treated with androgen-deprivation therapy and radiation
      therapy were randomly assigned to 6 mo of supervised exercise followed by 6 mo of
      a home-based maintenance programme (n=50) or printed educational material about
      physical activity (n=50) for 12 mo across 13 university-affiliated exercise
      clinics in Australia and New Zealand. INTERVENTION: Supervised resistance and
      aerobic exercise or printed educational material about physical activity. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was a 400-m walk as
      a measure of cardiovascular fitness. Secondary end points were physical function,
      patient-reported outcomes, muscle strength, body composition, and biomarkers.
      Analysis of covariance was used to compare outcomes for groups at 6 and 12 mo
      adjusted for baseline values. RESULTS AND LIMITATIONS: Participants undergoing
      supervised exercise showed improvement in cardiorespiratory fitness performance
      at 6 mo (-19 s [p=0.029]) and 12 mo (-13 s [p=0.028]) and better lower-body
      physical function across the 12-mo period (p<0.01). Supervised exercise also
      improved self-reported physical functioning at 6 (p=.006) and 12 mo (p=0.002),
      appendicular skeletal muscle at 6 mo (p=0.019), and objective measures of muscle
      strength at 6 and 12 mo (p<0.050). Limitations included the restricted number of
      participants undertaking body composition assessment, no blinding to group
      assignment for physical functioning measures, and inclusion of well-functioning
      individuals. CONCLUSIONS: Supervised exercise training in long-term PCa survivors
      is more effective than physical activity educational material for increasing
      cardiorespiratory fitness, physical function, muscle strength, and self-reported
      physical functioning at 6 mo. Importantly, these benefits were maintained in the
      long term with a home-based programme with follow-up at 12 mo. CLINICAL TRIAL
      REGISTRY: The effect of an exercise intervention on cardiovascular and metabolic
      risk factors in prostate cancer patients from the RADAR study, ACTRN:
      ACTRN12609000729224.

PMID- 24113320
TI  - Reply to Donald L. Lamm and Nilay M. Gandhi's letter to the editor re: Behfar
      Ehdaie, Richard Sylvester, Harry W. Herr. Maintenance bacillus Calmette-Guerin
      treatment of non-muscle-invasive bladder cancer: a critical evaluation of the
      evidence. Eur Urol 2013;64:579-85.

PMID- 24113321
TI  - Sex and age differences in the effect of obesity on incidence of hypertension in
      the Japanese population: A large historical cohort study.
AB  - Elevated risk of death from any cause and stroke associated with high body mass
      index (BMI) values decline with aging. However, it is not clear whether the
      effect of obesity on the incidence of hypertension varies by sex or age. Cox
      regression analyses were performed using a large historical cohort composed of
      6803 men and 22,800 women. In the final model, which included the main effect
      (sex, age, and BMI), all two-way interactions (sex*age, sex*BMI, and age*BMI), a
      three-way interaction (sex*age*BMI), and adjusted variables determined by
      backward elimination, the three-way interaction and two of the two-way
      interactions (age*sex and age*BMI) were not significant; the remaining two-way
      interaction between sex and BMI was significant (P = .016). In the next step, the
      effect of BMI on the incidence of hypertension stratified by sex was evaluated.
      Hazard ratios (HRs) were significantly higher for BMI 27.0 to <29.0 and >=29.0
      kg/m(2) than for the HR for BMI 21.0 to <23.0 kg/m(2) in women (HR, 1.45; 95%
      confidence interval [CI], 1.32-1.59 and HR, 1.46; 95% CI, 1.29-1.65,
      respectively), but not in men (HR, 1.14; 95% CI, 0.98-1.33 and HR, 1.01; 95% CI,
      0.77-1.32, respectively). The effect of obesity on the incidence of hypertension
      is stronger in women than in men.

PMID- 24113322
TI  - The depletion of donor macrophages reduces ischaemia-reperfusion injury after
      mouse lung transplantation.
AB  - OBJECTIVES: Macrophages (M) are one of the most important cells of the innate
      immune system for first line defense. Upon transplantation (Tx), M play a
      prominent role during lung ischaemia reperfusion (I/R) injury. Here, we
      hypothesize that the depletion of donor M ameliorates the post-transplant lung
      I/R injury. METHODS: Orthotopic single-lung Tx was performed between syngeneic
      BALB/c mice after a cold ischaemic time of 8 h and a reperfusion time of 10 h.
      Prior to graft implantation, alveolar macrophages of donor lungs were selectively
      depleted applying the 'suicide technique' by intratracheal application of
      clodronate liposomes (experimental, n = 6) vs the application of empty liposomes
      (control, n = 6). Cell count (number of F4/80(+)-macrophages) and graft injury
      were evaluated by histology and immunohistochemistry, and levels of lactat
      dehydrogenase (LDH) (apoptosis assay), enzyme linked immunosorbent assay for
      nuclear protein high-mobility-group-protein B1 (HMGB1), tumor necrosis factor
      alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in plasma were
      analysed. RESULTS: Clodronate liposomes successfully reduced 70% of M from donor
      lungs when compared with grafts treated with empty liposome only. M-depleted
      transplants showed improved histology and revealed considerably less graft damage
      when compared with control recipients (LDH, P = 0.03; HMGB1, P = 0.3).
      Oxygenation capacity was ameliorated in M-depleted transplants, if not
      significant (P = 0.114); however, wet/dry ratio did not differ between groups (P
      = 0.629). The inflammatory response was significantly reduced in M-depleted mice
      when compared with control recipients (TNF-alpha, P = 0.042; TGF-beta1, P =
      0.039). CONCLUSIONS: The selective depletion of M in donor lung transplants can
      be successfully performed and results in a sustained anti-inflammatory response
      upon I/R-injury. The beneficial effect of this preconditioning method should be
      further evaluated as a promising tool for the attenuation of I/R prior to graft
      implantation in clinical Tx.

PMID- 24113324
TI  - Direct comparison of adjacent endocardial and epicardial electrograms:
      implications for substrate mapping.
AB  - BACKGROUND: Analysis of unipolar voltage maps has been used to detect epicardial
      scar, but data to define optimal parameters to identify scar remote from the
      recording site is limited. This study compares the characteristics of
      electrograms at endocardial sites adjacent to abnormal epicardial sites. METHODS
      AND RESULTS: Data obtained from endocardial and epicardial electroanatomical maps
      of 31 patients with scar-related ventricular tachycardia were reviewed. Five
      hundred twenty-three pairs of endo- and epicardial points were selected according
      to predefined criteria. The endocardial points adjacent to epicardial scar
      (bipolar voltage < 1.5 mV) had smaller unipolar voltage than those distant from
      epicardial scar (P < 0.001). In multivariable analysis, unipolar voltage was the
      only endocardial electrogram predictor of epicardial scar (P < 0.001, OR 0.94,
      95% CI 0.93 to 0.97). An endocardial unipolar amplitude < 4.4 mV in the right
      ventricular (RV) (sensitivity 93%, specificity 76%) and < 5.1 mV in the left
      ventricular (LV) (sensitivity 91%, specificity 75%) was the optimal cutoff
      predicting epicardial scar. Applying these thresholds to electroanatomical maps,
      revealed a good match between endocardial unipolar abnormality and epicardial
      scar for 67% of LV and 75% of RV maps, respectively, but notably poor matches
      occurred in 8 (29%) maps (7 with nonischemic cardiomyopathy). Site-by-site
      correlations were better for ischemic than nonischemic cardiomyopathy.
      CONCLUSIONS: This study supports the contention that unipolar electrograms are
      capable of indicating overlying epicardial scar during endocardial mapping, but
      illustrates limitations that appear to differ with nonischemic as compared to
      ischemic cardiomyopathy. The presence of epicardial arrhythmia substrate cannot
      be excluded by analysis of unipolar endocardial maps in some patients.

PMID- 24113323
TI  - Critical involvement of the motor cortex in the pathophysiology and treatment of
      Parkinson's disease.
AB  - This review examines the involvement of the motor cortex in Parkinson's disease
      (PD), a debilitating movement disorder typified by degeneration of dopamine cells
      of the substantia nigra. While much of PD research has focused on the
      caudate/putamen, many aspects of motor cortex function are abnormal in PD
      patients and in animal models of PD, implicating motor cortex involvement in
      disease symptoms and their treatment. Herein, we discuss several lines of
      evidence to support this hypothesis. Dopamine depletion alters regional
      metabolism in the motor cortex and also reduces interneuron activity, causing a
      breakdown in intracortical inhibition. This leads to functional reorganization of
      motor maps and excessive corticostriatal synchrony when movement is initiated.
      Recent work suggests that electrical stimulation of the motor cortex provides a
      clinical benefit for PD patients. Based on extant research, we identify a number
      of unanswered questions regarding the motor cortex in PD and argue that a better
      understanding of the contribution of the motor cortex to PD symptoms will
      facilitate the development of novel therapeutic approaches. 

PMID- 24113325
TI  - Circulating omega-3 polyunsaturated fatty acids and subclinical brain
      abnormalities on MRI in older adults: the Cardiovascular Health Study.
AB  - BACKGROUND: Consumption of tuna or other broiled or baked fish, but not fried
      fish, is associated with fewer subclinical brain abnormalities on magnetic
      resonance imaging (MRI). We investigated the association between plasma
      phospholipid omega-3 polyunsaturated fatty acids (PUFAs), objective biomarkers of
      exposure, and subclinical brain abnormalities on MRI. METHODS AND RESULTS: In the
      community-based Cardiovascular Health Study, 3660 participants aged >= 65
      underwent brain MRI in 1992-1994, and 2313 were rescanned 5 years later. MRIs
      were centrally read by neuroradiologists in a standardized, blinded manner.
      Participants with recognized transient ischemic attacks or stroke were excluded.
      Phospholipid PUFAs were measured in stored plasma collected in 1992-1993 and
      related to cross-sectional and longitudinal MRI findings. After multivariable
      adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60
      (95% CI, 0.44 to 0.82; P for trend = 0.001) in the highest versus lowest long
      chain omega-3 PUFA quartile. Higher long-chain omega-3 PUFA content was also
      associated with better white matter grade, but not with sulcal or ventricular
      grades, markers of brain atrophy, or with incident subclinical infarcts. The
      phospholipid intermediate-chain omega-3 PUFA alpha-linolenic acid was associated
      only with modestly better sulcal and ventricular grades. However, this finding
      was not supported in the analyses with alpha-linolenic acid intake. CONCLUSIONS:
      Among older adults, higher phospholipid long-chain omega-3 PUFA content was
      associated with lower prevalence of subclinical infarcts and better white matter
      grade on MRI. Our results support the beneficial effects of fish consumption, the
      major source of long-chain omega-3 PUFAs, on brain health in later life. The role
      of plant-derived alpha-linolenic acid in brain health requires further
      investigation.

PMID- 24113326
TI  - The advancing field of cell-based therapy: insights and lessons from clinical
      trials.

PMID- 24113327
TI  - Cellular encapsulation enhances cardiac repair.
AB  - BACKGROUND: Stem cells for cardiac repair have shown promise in preclinical
      trials, but lower than expected retention, viability, and efficacy. Encapsulation
      is one potential strategy to increase viable cell retention while facilitating
      paracrine effects. METHODS AND RESULTS: Human mesenchymal stem cells (hMSC) were
      encapsulated in alginate and attached to the heart with a hydrogel patch in a rat
      myocardial infarction (MI) model. Cells were tracked using bioluminescence (BLI)
      and cardiac function measured by transthoracic echocardiography (TTE) and cardiac
      magnetic resonance imaging (CMR). Microvasculature was quantified using von
      Willebrand factor staining and scar measured by Masson's Trichrome. Post-MI
      ejection fraction by CMR was greatly improved in encapsulated hMSC-treated
      animals (MI: 34 +/- 3%, MI + Gel: 35 +/- 3%, MI + Gel + hMSC: 39 +/- 2%, MI + Gel
      + encapsulated hMSC: 56 +/- 1%; n = 4 per group; P < 0.01). Data represent mean
      +/- SEM. By TTE, encapsulated hMSC-treated animals had improved fractional
      shortening. Longitudinal BLI showed greatest hMSC retention when the cells were
      encapsulated (P < 0.05). Scar size at 28 days was significantly reduced in
      encapsulated hMSC-treated animals (MI: 12 +/- 1%, n = 8; MI + Gel: 14 +/- 2%, n =
      7; MI + Gel + hMSC: 14 +/- 1%, n = 7; MI+Gel+encapsulated hMSC: 7 +/- 1%, n = 6;
      P < 0.05). There was a large increase in microvascular density in the peri
      infarct area (MI: 121 +/- 10, n = 7; MI + Gel: 153 +/- 26, n = 5; MI + Gel +
      hMSC: 198 +/- 18, n = 7; MI + Gel + encapsulated hMSC: 828 +/- 56 vessels/mm2, n
      = 6; P < 0.01). CONCLUSIONS: Alginate encapsulation improved retention of hMSCs
      and facilitated paracrine effects such as increased peri-infarct microvasculature
      and decreased scar. Encapsulation of MSCs improved cardiac function post-MI and
      represents a new, translatable strategy for optimization of regenerative
      therapies for cardiovascular diseases.

PMID- 24113328
TI  - More or less irregularity in understanding an irregular rhythm: atrial
      fibrillation classification and racial differences.

PMID- 24113329
TI  - EEG driving response during low-frequency stimulation of anterior thalamic
      nucleus: Is it a good predictor of the correct location of DBS electrode?

PMID- 24113330
TI  - Mismatch Negativity in essential tremor: role of age at onset in pre-attentive
      auditory discrimination.
AB  - OBJECTIVE: To investigate whether pre-attentive auditory discrimination is
      impaired in patients with essential tremor (ET) and to evaluate the role of age
      at onset in this function. METHODS: Seventeen non-demented patients with ET and
      seventeen age- and sex-matched healthy controls underwent an EEG recording during
      a classical auditory MMN paradigm. RESULTS: MMN latency was significantly
      prolonged in patients with elderly-onset ET (>65 years) (p=0.046), while no
      differences emerged in either latency or amplitude between young-onset ET
      patients and controls. CONCLUSIONS: This study represents a tentative indication
      of a dysfunction of auditory automatic change detection in elderly-onset ET
      patients, pointing to a selective attentive deficit in this subgroup of ET
      patients. SIGNIFICANCE: The delay in pre-attentive auditory discrimination, which
      affects elderly-onset ET patients alone, further supports the hypothesis that ET
      represents a heterogeneous family of diseases united by tremor; these diseases
      are characterized by cognitive differences that may range from a disturbance in a
      selective cognitive function, such as the automatic part of the orienting
      response, to more widespread and complex cognitive dysfunctions.

PMID- 24113331
TI  - Possible second motor neuron damage in neuromyelitis optica.

PMID- 24113332
TI  - A tetrazine templated method for the synthesis of ternary conjugates.
AB  - Conjugation is an important reaction that enables coupling of molecules. Many
      protocols exist for the synthesis of binary conjugates from two different
      molecules or for the polyvalent display of a single molecule. There aren't many
      methods for the synthesis of ternary conjugates. However, methods for ternary
      conjugation are important for understanding the interplay of interactions between
      three biomolecules (or any three molecules per se). A strategy for ternary
      bioconjugation using inverse electron demand Diels-Alder reaction with tetrazine
      is studied. Ternary conjugation was demonstrated by the reaction of a model glyco
      peptide binary conjugate with a fluorescent tagged olefin. 

PMID- 24113333
TI  - Stability of core-shell magnetite nanoparticles.
AB  - In the paper, we present three different types of magnetite nanoparticles which
      were prepared from co-percipitation of iron (II) and (III) chlorides in aqueous
      solution with and without SiO2 and from thermal decomposition of iron (III)
      acetylacetonate in nonaqeous solutions. The obtained core-shell nanoparticles
      were tested in respect of their stability in distilled water, 10% acetic acid,
      0.01 M citric acid, 0.9% NaCl and commercial white wine (12% of alcohol). Changes
      of the nanoparticles were examined by infrared spectroscopy, atomic absorption
      spectroscopy, transmission electron microscopy, X-ray diffraction and
      differential scanning calorimetry methods. Modification of magnetic properties
      was measured by Mossbauer spectroscopy.

PMID- 24113334
TI  - Atomistic simulations of stainless steels: a many-body potential for the Fe-Cr-C
      system.
AB  - Stainless steels found in real-world applications usually have some C content in
      the base Fe-Cr alloy, resulting in hard and dislocation-pinning carbides-Fe3C
      (cementite) and Cr23C6-being present in the finished steel product. The higher
      complexity of the steel microstructure has implications, for example, for the
      elastic properties and the evolution of defects such as Frenkel pairs and
      dislocations. This makes it necessary to re-evaluate the effects of basic
      radiation phenomena and not simply to rely on results obtained from purely
      metallic Fe-Cr alloys. In this report, an analytical interatomic potential
      parameterization in the Abell-Brenner-Tersoff form for the entire Fe-Cr-C system
      is presented to enable such calculations. The potential reproduces, for example,
      the lattice parameter(s), formation energies and elastic properties of the
      principal Fe and Cr carbides (Fe3C, Fe5C2, Fe7C3, Cr3C2, Cr7C3, Cr23C6), the Fe
      Cr mixing energy curve, formation energies of simple C point defects in Fe and
      Cr, and the martensite lattice anisotropy, with fair to excellent agreement with
      empirical results. Tests of the predictive power of the potential show, for
      example, that Fe-Cr nanowires and bulk samples become elastically stiffer with
      increasing Cr and C concentrations. High-concentration nanowires also fracture at
      shorter relative elongations than wires made of pure Fe. Also, tests with Fe3C
      inclusions show that these act as obstacles for edge dislocations moving through
      otherwise pure Fe.

PMID- 24113335
TI  - Cobalt monoxide-doped porous graphitic carbon microspheres for supercapacitor
      application.
AB  - A novel design and facile synthesis process for carbon based hybrid materials,
      i.e., cobalt monoxide (CoO)-doped graphitic porous carbon microspheres (Co
      GPCMs), have been developed. With the synthesis strategy, the mixture of cobalt
      gluconate, alpha-cyclodextrin and poly (ethylene oxide)106-poly (propylene
      oxide)70-poly (ethylene oxide)106 is treated hydrothermally, followed by
      pyrolysis in argon. The resultant Co-GPCMs exhibits a porous carbon matrix with
      localized graphitic structure while CoO nanodots are embedded in the carbon
      frame. Thus, the Co-GPCMs effectively combine the electric double-layer
      capacitance and pseudo-capacitance when used as the electrode in supercapacitor,
      which lead to a higher operation voltage (1.6 V) and give rise to a significantly
      higher energy density. This study provides a new research strategy for electrode
      materials in high energy density supercapacitors.

PMID- 24113336
TI  - Predicting clinically significant changes in motor and functional outcomes after
      robot-assisted stroke rehabilitation.
AB  - OBJECTIVE: To investigate the predictors of minimal clinically important changes
      on outcome measures after robot-assisted therapy (RT). DESIGN: Observational
      cohort study. SETTING: Outpatient rehabilitation clinics. PARTICIPANTS: A cohort
      of outpatients with stroke (N=55). INTERVENTIONS: Patients with stroke received
      RT for 90 to 105min/d, 5d/wk, for 4 weeks. MAIN OUTCOME MEASURES: Outcome
      measures, including the Fugl-Meyer Assessment (FMA) and Motor Activity Log (MAL),
      were measured before and after the intervention. Potential predictors include
      age, sex, side of lesion, time since stroke onset, finger extension, Box and
      Block Test (BBT) score, and FMA distal score. RESULTS: Statistical analysis
      showed that the BBT score (odds ratio[OR]=1.06; P=.04) was a significant
      predictor of clinically important changes in the FMA. Being a woman (OR=3.9;
      P=.05) and BBT score (OR=1.07; P=.02) were the 2 significant predictors of
      clinically significant changes in the MAL amount of use subscale. The BBT score
      was the significant predictor of an increased probability of achieving clinically
      important changes in the MAL quality of movement subscale (OR=1.07; P=.02). The
      R(2) values for the 3 logistic regression models were low (.114-.272).
      CONCLUSIONS: The results revealed that patients with stroke who had greater
      manual dexterity measured by the BBT appear to have a higher probability of
      achieving clinically significant motor and functional outcomes after RT. Further
      studies are needed to evaluate other potential predictors to improve the models
      and validate the findings.

PMID- 24113337
TI  - Prestroke weight loss is associated with poststroke mortality among men in the
      Honolulu-Asia Aging Study.
AB  - OBJECTIVE: To examine baseline prestroke weight loss and poststroke mortality
      among men. DESIGN: Longitudinal study of late-life prestroke body mass index
      (BMI), weight loss, and BMI change (midlife to late life) with up to 8-year
      incident stroke and mortality follow-up. SETTING: Community-based aging study
      data. PARTICIPANTS: Japanese-American men (N=3581; age range, 71-93y) who were
      stroke free at baseline. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      Poststroke mortality: 30 days poststroke, analyzed with stepwise multivariable
      logistic regression; and long-term poststroke (up to 8y), analyzed with stepwise
      multivariable Cox regression. RESULTS: Weight loss (4.5kg decrements) was
      associated with increased 30-day poststroke mortality (adjusted odds ratio=1.48;
      95% confidence interval [CI], 1.14-1.92), long-term mortality after incident
      stroke (all types, n=225; adjusted hazards ratio (aHR)=1.25; 95% CI, 1.09-1.44),
      and long-term mortality after incident thromboembolic stroke (n=153; aHR=1.19;
      95% CI, 1.01 to 1.40). Men with overweight/obese late-life BMI (>=25kg/m(2),
      compared with healthy/underweight BMI) had increased long-term mortality after
      incident hemorrhagic stroke (n=54; aHR=2.27; 95% CI, 1.07-4.82). Neither
      desirable nor excessive BMI reductions (vs no change/increased BMI) were
      associated with poststroke mortality. In the overall sample (N=3581), nutrition
      factors associated with increased long-term mortality included the following: (1)
      weight loss (10lb decrements; aHR=1.15; 95% CI, 1.09-1.21), (2) underweight BMI
      (vs healthy BMI; aHR=1.76; 95% CI, 1.40-2.20), and (3) both desirable and
      excessive BMI reductions (vs no change or gain, separate model from weight loss
      and BMI; aHR range, 1.36-1.97; P<.001). CONCLUSIONS: Although obesity is a risk
      factor for stroke incidence, prestroke weight loss was associated with increased
      poststroke (all types and thromboembolic) mortality. Overweight/obese late-life
      BMI was associated with increased posthemorrhagic stroke mortality. Desirable and
      excessive BMI reductions were not associated with poststroke mortality. Weight
      loss, underweight late-life BMI, and any BMI reduction were all associated with
      increased long-term mortality in the overall sample.

PMID- 24113339
TI  - Comparison of sedentary behaviors between children with autism spectrum disorders
      and typically developing children.
AB  - Time spent in sedentary behavior is largely due to time spent engaged with
      electronic screen media. Little is known about the extent to which sedentary
      behaviors for children with autism spectrum disorder differ from typically
      developing children. We used parental report to assess and compare time spent in
      sedentary behaviors for 53 children with autism spectrum disorder and 58
      typically developing children aged 3-11 years. We also determined how sedentary
      behavior was related to child weight status (body mass index z-score). Overall,
      children with autism spectrum disorder spent an hour more in sedentary behaviors
      on weekdays compared to typically developing children (5.2 vs 4.2 h, p = 0.03),
      and most of this difference was due to screen time. The age- and sex-adjusted
      estimate of weekday total daily screen time was 1.6 h (typically developing)
      compared to 2.5 h (autism spectrum disorder, p = 0.004 for difference). A
      significant relationship between BMI z-score and total sedentary behavior time on
      weekend days was observed among young children with ASD, but not among TD
      children. The modest association between weekend sedentary behaviour time and BMI
      z-score among children with ASD suggests that sedentary behaiour is linked to
      relative weight status in these children. Further research is needed to confirm
      these findings and identify causal pathways. 

PMID- 24113340
TI  - Effects of repetitive transcranial magnetic stimulation in performing eye-hand
      integration tasks: four preliminary studies with children showing low-functioning
      autism.
AB  - This report, based on four studies with children with low-functioning autism,
      aimed at evaluating the effects of repetitive transcranial magnetic stimulation
      delivered on the left and right premotor cortices on eye-hand integration tasks;
      defining the long-lasting effects of high-frequency repetitive transcranial
      magnetic stimulation; and investigating the real efficacy of high-frequency
      repetitive transcranial magnetic stimulation by comparing three kinds of
      treatments (high-frequency repetitive transcranial magnetic stimulation, a
      traditional eye-hand integration training, and both treatments combined). Results
      showed a significant increase in eye-hand performances only when high-frequency
      repetitive transcranial magnetic stimulation was delivered on the left premotor
      cortex; a persistent improvement up to 1 h after the end of the stimulation;
      better outcomes in the treatment combining high-frequency repetitive transcranial
      magnetic stimulation and eye-hand integration training. Based on these
      preliminary findings, further evaluations on the usefulness of high-frequency
      repetitive transcranial magnetic stimulation in rehabilitation of children with
      autism are strongly recommended. 

PMID- 24113341
TI  - Training of child and adolescent psychiatry fellows in autism and intellectual
      disability.
AB  - Patients with autism spectrum disorders and intellectual disability can be
      clinically complex and often have limited access to psychiatric care. Because
      little is known about post-graduate clinical education in autism spectrum
      disorder and intellectual disability, we surveyed training directors of child and
      adolescent psychiatry fellowship programs. On average, child and adolescent
      psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum
      disorder and intellectual disability, respectively. Training directors commonly
      reported that trainees see 1-5 patients with autism spectrum disorder or
      intellectual disability per year for outpatient pharmacological management and
      inpatient treatment. Overall, 43% of directors endorsed the need for additional
      resources for training in autism spectrum disorder and intellectual disability,
      which, coupled with low didactic and clinical exposure, suggests that current
      training is inadequate. 

PMID- 24113342
TI  - Investigating the cross-cultural validity of DSM-5 autism spectrum disorder:
      evidence from Finnish and UK samples.
AB  - The recent Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition
      (DSM-5) reformulation of autism spectrum disorder has received empirical support
      from North American and UK samples. Autism spectrum disorder is an increasingly
      global diagnosis, and research is needed to discover how well it generalises
      beyond North America and the United Kingdom. We tested the applicability of the
      DSM-5 model to a sample of Finnish young people with autism spectrum disorder (n
      = 130) or the broader autism phenotype (n = 110). Confirmatory factor analysis
      tested the DSM-5 model in Finland and compared the fit of this model between
      Finnish and UK participants (autism spectrum disorder, n = 488; broader autism
      phenotype, n = 220). In both countries, autistic symptoms were measured using the
      Developmental, Diagnostic and Dimensional Interview. Replicating findings from
      English-speaking samples, the DSM-5 model fitted well in Finnish autism spectrum
      disorder participants, outperforming a Diagnostic and Statistical Manual of
      Mental Disorders-Fourth Edition (DSM-IV) model. The DSM-5 model fitted equally
      well in Finnish and UK autism spectrum disorder samples. Among broader autism
      phenotype participants, this model fitted well in the United Kingdom but poorly
      in Finland, suggesting that cross-cultural variability may be greatest for milder
      autistic characteristics. We encourage researchers with data from other cultures
      to emulate our methodological approach, to map any cultural variability in the
      manifestation of autism spectrum disorder and the broader autism phenotype. This
      would be especially valuable given the ongoing revision of the International
      Classification of Diseases-11th Edition, the most global of the diagnostic
      manuals. 

PMID- 24113343
TI  - Maternal verbal responses to communication of infants at low and heightened risk
      of autism.
AB  - This study investigates mothers' responses to infant communication among infants
      at heightened genetic risk (high risk) of autism spectrum disorder compared to
      infants with no such risk (low risk). A total of 26 infants, 12 of whom had an
      older sibling with autism spectrum disorder, were observed during naturalistic in
      home interaction and semistructured play with their mothers at 13 and 18 months
      of age. Results indicate that overall, mothers of low-risk and high-risk infants
      were highly and similarly responsive to their infants' communicative behaviors.
      However, examination of infant vocal and gestural communication development
      together with maternal verbal responses and translations (i.e. verbally labeling
      a gesture referent) suggests that delays in early communication development
      observed among high-risk infants may alter the input that these infants receive;
      this in turn may have cascading effects on the subsequent development of
      communication and language.

PMID- 24113344
TI  - Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy:
      importance of periodic reassessment.
AB  - PURPOSE: Major advances have been made in our understanding and clinical
      application of genetic testing in hypertrophic cardiomyopathy. Determining
      pathogenicity of a single-nucleotide variant remains a major clinical challenge.
      This study sought to reassess single-nucleotide variant classification in
      hypertrophic cardiomyopathy probands. METHODS: Consecutive probands with
      hypertrophic cardiomyopathy with a reported pathogenic mutation or variation of
      uncertain significance were included. Family and medical history were obtained.
      Each single-nucleotide variant was reassessed by a panel of four reviewers for
      pathogenicity based on established criteria together with updated cosegregation
      data and current population-based allele frequencies. RESULTS: From 2000 to 2012,
      a total of 136 unrelated hypertrophic cardiomyopathy probands had genetic
      testing, of which 63 (46%) carried at least one pathogenic mutation. MYBPC3 (n =
      34; 47%) and MYH7 (n = 23; 32%) gene variants together accounted for 79%. Five
      variants in six probands (10%) were reclassified: two variation of uncertain
      significance were upgraded to pathogenic, one variation of uncertain significance
      and one pathogenic variant were downgraded to benign, and one pathogenic variant
      (found in two families) was downgraded to variation of uncertain significance.
      None of the reclassifications had any adverse clinical consequences. CONCLUSION:
      Given the rapid growth of genetic information available in both disease and
      normal populations, periodic reassessment of single-nucleotide variant data is
      essential in hypertrophic cardiomyopathy.

PMID- 24113345
TI  - Patient decisions for disclosure of secondary findings among the first 200
      individuals undergoing clinical diagnostic exome sequencing.
AB  - PURPOSE: Exome sequencing of a single individual for a clinical indication may
      result in the identification of incidental deleterious variants unrelated to the
      indication for testing (secondary findings). Given the recent availability of
      clinical exome testing, there is a limited knowledge regarding the disclosure
      preferences and impact of secondary findings in a clinical diagnostic setting. In
      this article, we provide preliminary data regarding the preferences for secondary
      findings results disclosure based on the first 200 families referred to Ambry
      Genetics for diagnostic exome sequencing. METHODS: Secondary findings were
      categorized into four groups in the diagnostic exome sequencing consent: carrier
      status of recessive disorders, predisposition to later-onset disease,
      predisposition to increased cancer risk, and early-onset disease. In this study,
      we performed a retrospective analysis of patient responses regarding the
      preferences for secondary findings disclosure. RESULTS: The majority of patients
      (187/200; 93.5%) chose to receive secondary results for one or more available
      categories. Adult probands were more likely than children to opt for blinding of
      secondary data (16 vs. 4%, respectively). Among responses for blinding,
      preferences were evenly scattered among categories. CONCLUSION: These data
      represent the unprecedented results of a large reference laboratory providing
      clinical exome sequencing. We report, for the first time, the preferences of
      patients and families for the receipt of secondary findings based on clinical
      genome sequencing. Overwhelmingly, families undergoing exome sequencing opt for
      the disclosure of secondary findings. The data may have implications regarding
      the development of guidelines for secondary findings reporting among patients
      with severe and/or life-threatening disease undergoing clinical genomic
      sequencing.

PMID- 24113346
TI  - The integration of next-generation sequencing panels in the clinical cancer
      genetics practice: an institutional experience.
AB  - PURPOSE: The advent of next-generation sequencing for cancer susceptibility genes
      holds promise for clinical genetics application, but the practical issues
      surrounding integration of this testing into the clinical setting have not been
      well addressed. This article describes the clinical experience of genetic
      counselors in an academic and community setting with next-generation sequencing
      cancer panels. METHODS: Between April 2012 and January 2013, 60 next-generation
      sequencing panels were ordered. A retrospective review was conducted to determine
      the indication for ordering the results of the tests and the patient management
      based on the results. RESULTS: Ten tests were canceled due to out-of-pocket costs
      or previously identified mutations. Among the 50 tests, 5 (10%) showed a positive
      result. Moreover, 15 of the 50 (30%) panels detected variant(s) of uncertain
      significance or variant(s) suspected benign. CONCLUSION: We propose clinical
      guidelines for identifying high-risk patients who should be offered this testing.
      Our data support the National Comprehensive Cancer Network recommendations that
      next-generation sequencing be ordered as a second-tier test for high-risk
      individuals with cancer by trained cancer genetics providers. Literature review
      and expert knowledge should be used to create management plans for the
      identification of both positive and variants of uncertain significance results.
      Providers should be aware of limitations regarding reimbursement for testing and
      recommended management strategies.

PMID- 24113347
TI  - Similar prevalence of expanded CGG repeat lengths in the fragile X mental
      retardation I gene among infertile women and among women with proven fertility: a
      prospective study.
AB  - PURPOSE: We sought to determine the usefulness of fragile X mental retardation 1
      (FMR1) carrier testing among young infertile women with or without signs of
      ovarian insufficiency as compared with fertile women. METHODS: Three cohorts of
      women were recruited to determine the cytosine-guanine-guanine (CGG) repeats
      trinucleotide repeat length in the 5'-untranslated region of the FMR1 gene in
      lymphocyte DNA. A total of 199 fertile women, who were reported to have conceived
      within 3 months, were recruited together with 372 infertile women with ongoing
      menstrual cycles and 48 infertile women with primary ovarian insufficiency. The
      various ranges of FMR1 CGG repeat lengths among infertile women were compared
      with those of fertile controls. In infertile women with ongoing menstrual cycles,
      the serum concentrations of follicle-stimulating hormone, anti-Muellerian
      hormone, and inhibin B were measured during the early follicular phase. RESULTS:
      None of the three categories of FMR1 CGG repeat length expansions (premutation,
      intermediate range, and high normal range) were more prevalent among infertile
      women than among fertile women. The CGG repeat length was not correlated with any
      of the ovarian reserve parameters. CONCLUSION: In comparison with a generalized
      preconception screening strategy, infertility as a criterion, even together with
      reduced ovarian reserve, is not suitable for identifying a higher proportion of
      women with expanded FMR1 CGG repeat length.

PMID- 24113348
TI  - Receptor for advanced glycation end-products promotes premature senescence of
      proximal tubular epithelial cells via activation of endoplasmic reticulum stress
      dependent p21 signaling.
AB  - Premature senescence is a key process in the progression of diabetic nephropathy
      (DN). In our study, we hypothesized that receptors for advanced glycation end
      products (RAGE) mediate endoplasmic reticulum (ER) stress to induce premature
      senescence via p21 signaling activation in diabetic nephropathy. Here, we
      demonstrated that elevated expression of RAGE, ER stress marker glucose-regulated
      protein 78 (GRP78), and cell-cycle regulator p21 was all positively correlated
      with enhanced senescence-associated-beta-galactosidase (SA-beta-gal) activity in
      DN patients. In addition, the fraction of SA-beta-gal or cells in the G0G1 phase
      were enhanced in cultured mouse proximal tubular epithelial cells (PTECs) and the
      expression of RAGE, GRP78 and p21 was up-regulated by advanced glycation end
      products (AGEs) in a dose- and time-dependent manner. Interestingly, ER stress
      inducers or RAGE overexpression mimicked AGEs induced-premature senescence, and
      this was significantly suppressed by p21 gene silencing. However, RAGE blocking
      successfully attenuated AGEs-induced ER stress and p21 expression, as well as
      premature senescence. Moreover, ER stress inducers directly caused p21
      activation, premature senescence, and also enhanced RAGE expression by positive
      feedback. These observations suggest that RAGE promotes premature senescence of
      PTECs by activation of ER stress-dependent p21 signaling. 

PMID- 24113349
TI  - LncRNA expression signatures of twist-induced epithelial-to-mesenchymal
      transition in MCF10A cells.
AB  - The epithelial-to-mesenchymal transient (EMT) is associated with tumor
      metastasis. Twist is one of the key transcription factors for EMT and relates to
      tumor cell migration. Long non-coding RNAs (lncRNAs) have recently emerged as
      important regulatory molecules involved in a broad range of biological processes
      and complicated diseases. However, it is unknown whether a signal network and
      lncRNAs are involved in Twist-induced EMT program. Taking MCF10A/Twist as a
      model, more than 99 lncRNAs and 3164 genes are regulated in the Twist-induced EMT
      process using lncRNA-array and cDNA micro-array. We establish a downstream signal
      network associated with EMT induced by Twist using bioinformatic analysis (Gene
      Ontology, pathway analysis) and experimental data. A set of multiple canonical
      signal pathways (such as WNT, MAPK, JAK/STAT, TGF-beta, mTOR, Hedgehog and P53
      signaling pathways) and several lncRNAs [such as lncRNA (chr6, 26124411-26139312,
      +), lncRNA (chr1, 41944445-41949874, -), lncRNA (chr17, 44833874-44834830, +)]
      are altered in MCF10A/Twist cells. More interestingly, lncRNA (chr17, 44833874
      44834830, +), lncRNA (chr17, 21142183-21156578, -), lncRNA (chr6, 26124411
      26139312, +) and lncRNA (chr19, 438420-2083745, -) may be involved in regulation
      or activation of WNT signaling pathway in the Twist-induced EMT process. These
      findings first determine that Twist contributes to invasion and metastasis by
      inducing wide-ranging transcriptional and functional changes of lncRNAs and
      signal pathways in our study. 

PMID- 24113350
TI  - Real-time image-guided recontouring in the management of craniofacial fibrous
      dysplasia.
AB  - OBJECTIVE: This report presents our experience using computer-aided recontouring
      in the surgical management of complex craniofacial fibrous dysplasia with the use
      of a navigation system developed by the authors. STUDY DESIGN: A total of 21
      patients (9 men and 12 women) with craniofacial fibrous dysplasia and mean age of
      23 years (range, 17-32 years) were included in this study from 2007 to 2012. By
      creating a mirror image of the unaffected side on the affected side as a virtual
      treatment template, we completed the recontouring procedures in real time with
      the aid of the navigation system that we developed (Accu-Navi). The surgical
      outcome was assessed by superimposing the postoperative computed tomography (CT)
      images onto the preoperative CT images. RESULTS: The precise preoperative
      simulation and intraoperative navigation enabled the surgeon to complete the
      recontouring procedure visually. Postoperative CT was compared with the
      preoperative plan, yielding an average discrepancy of <1.0 mm. Postoperative
      follow-up found that both facial aesthetics and patient satisfaction improved
      remarkably. CONCLUSIONS: Navigation-guided recontouring shows benefits in
      improving accuracy and safety for this complicated procedure.

PMID- 24113351
TI  - Reconstruction of a complex midface defect from excision of a squamous cell
      carcinoma, according to regional aesthetic units.
AB  - Extensive squamous cell carcinoma involving the skin of the upper lip, nasal ala,
      and cheek is relatively rare. Although numerous reconstruction techniques for the
      midface including lip, nose, and cheek have been described in the literature,
      reconstruction of large defects in this area continues to be challenging, as it
      is difficult to obtain satisfactory results with single-stage surgery. This case
      report concerns a 53-year-old woman with squamous cell carcinoma extending from
      the upper lip to the alar base and the cheek. It describes a step-by-step surgery
      undertaken according to defined regional aesthetic units of the face using
      several reconstruction methods, including a microvascular free flap, forehead
      flap, and conchal cartilage graft, rather than multistage reconstruction
      surgeries after first immediate reconstruction. Satisfactory functional and
      aesthetic results were achieved despite the extensive facial defects.

PMID- 24113352
TI  - Is preoperative brain midline shift a determinant factor for neurological
      improvement after cranioplasty?
AB  - BACKGROUND/PURPOSE: In patients with traumatic brain injury, the degree of brain
      midline shift is related to prognosis. In this study, we evaluated the impact of
      the presence of a preoperative brain midline shift on the Glasgow Coma Scale
      (GCS) scores and muscle power (MP) improvement after cranioplasty. METHODS: In
      this 6-year retrospective cohort study, we compared cranioplasty patients from
      Taiwan with and without a preoperative brain midline shift. We assigned the
      patients to the following two groups: the midline shift group and the nonmidline
      shift group. The GCS score and MP contralateral to the lesion site were recorded
      and analyzed both prior to and 1 year after the operation. RESULTS: We enrolled
      56 cranioplasty patients (35 patients with a midline shift and 21 without a
      midline shift) and analyzed their complete clinical characteristics. There were
      significant improvements in the GCS (p = 0.0078), arm MP (p = 0.0056), and leg MP
      (p = 0.0006) scores after cranioplasty. There was also a significant improvement
      in the GCS score in the brain midline shift group (0.4 +/- 0.149 in the brain
      midline shift group vs. 0.05 +/- 0.48 in the nonmidline shift group, p = 0.03).
      CONCLUSION: For patients who underwent craniectomy, an improvement in
      neurological function 1 year after cranioplasty was observed. The patients with
      brain midline shift showed more improvement in consciousness after cranioplasty
      than those without a brain midline shift. The presence of a preoperative brain
      midline shift may be an isolated determinant for the prediction of the outcome
      after cranioplasty.

PMID- 24113353
TI  - A new single crystal diamond dosimeter for small beam: comparison with different
      commercial active detectors.
AB  - Recent developments of new therapy techniques using small photon beams, such as
      stereotactic radiotherapy, require suitable detectors to determine the delivered
      dose with a high accuracy. The dosimeter has to be as close as possible to tissue
      equivalence and to exhibit a small detection volume compared to the size of the
      irradiation field, because of the lack of lateral electronic equilibrium in small
      beam. Characteristics of single crystal diamond (tissue equivalent material Z =
      6, high density) make it an ideal candidate to fulfil most of small beam
      dosimetry requirements. A commercially available Element Six electronic grade
      synthetic diamond was used to develop a single crystal diamond dosimeter (SCDDo)
      with a small detection volume (0.165 mm(3)). Long term stability was studied by
      irradiating the SCDDo in a (60)Co beam over 14 h. A good stability (deviation
      less than +/- 0.1%) was observed. Repeatability, dose linearity, dose rate
      dependence and energy dependence were studied in a 10 * 10 cm(2) beam produced by
      a Varian Clinac 2100 C linear accelerator. SCDDo lateral dose profile, depth dose
      curve and output factor (OF) measurements were performed for small photon beams
      with a micro multileaf collimator m3 (BrainLab) attached to the linac. This study
      is focused on the comparison of SCDDo measurements to those obtained with
      different commercially available active detectors: an unshielded silicon diode
      (PTW 60017), a shielded silicon diode (Sun Nuclear EDGE), a PinPoint ionization
      chamber (PTW 31014) and two natural diamond detectors (PTW 60003). SCDDo presents
      an excellent spatial resolution for dose profile measurements, due to its small
      detection volume. Low energy dependence (variation of 1.2% between 6 and 18 MV
      photon beam) and low dose rate dependence of the SCDDo (variation of 1% between
      0.53 and 2.64 Gy min(-1)) are obtained, explaining the good agreement between the
      SCDDo and the efficient unshielded diode (PTW 60017) in depth dose curve
      measurements. For field sizes ranging from 0.6 * 0.6 to 10 * 10 cm(2), OFs
      obtained with the SCDDo are between the OFs measured with the PinPoint ionization
      chamber and the Sun Nuclear EDGE diode that are known to respectively
      underestimate and overestimate OF values in small beam, due to the large
      detection volume of the chamber and the non-water equivalence of both detectors. 

PMID- 24113354
TI  - Dependence of global superconductivity on inter-island coupling in arrays of long
      SNS junctions.
AB  - We present measurements of the superconducting transition temperature, Tc, for
      arrays of mesoscopic Nb islands patterned on Au films, for large island spacings
      d. We show that Tc ~ 1/d(2), and explain this dependence in terms of the
      quasiclassical prediction that the Thouless energy, rather than the
      superconducting gap, governs the inter-island coupling at large spacings. We also
      find that the temperature dependence of the critical current, Ic(T), in our
      arrays is similar to that of single SNS junctions. However, our results deviate
      from the quasiclassical theory in that Tc is sensitive to island height, because
      the islands are mesoscopic.

PMID- 24113355
TI  - Leigh syndrome with Fukuyama congenital muscular dystrophy: a case report.
AB  - We report the first case of Leigh syndrome (LS) with Fukuyama congenital muscular
      dystrophy (FCMD). A neonate suffered from lactic acidosis and subsequently
      presented with poor feeding, muscle weakness, hypotonia, cardiopulmonary
      dysfunction, and hydrocephalus. He died at 17 months. The findings of brain
      magnetic resonance imaging indicated some specific features of both LS and FCMD,
      and FCMD gene mutation was detected. Decreased mitochondrial respiratory complex
      I and II activity was noted. Mitochondrial DNA sequencing showed no pathogenic
      mutation. A case with complex I+II deficiency has rarely been reported,
      suggesting a nuclear gene mutation.

PMID- 24113356
TI  - Foreword. New frontiers in molecular and cellular therapy.

PMID- 24113357
TI  - New targets in pediatric Acute Myeloid Leukemia.
AB  - In the last few years the improvements of chemotherapy regimens and supportive
      care has progressively ameliorated the prognosis of children suffering from Acute
      Myeloid Leukemia (AML). However, a still high percentage of children do not
      respond to first line treatments or relapse and need to undergo further
      treatments. The need to explore new agents other than chemotherapy has been
      highlighted in the last years in order to overcome drug related resistance and
      toxicity. Recently, novel therapies have been studied within early phases
      pediatric trials and seem to show encouraging results. In fact, the knowledge of
      molecular abnormalities related to AML pathogenesis has permitted to identify
      selective drugs that may represent an important tool for the development of
      patient-tailored treatments. Nowadays, FLT3, Aurora Kinases, mTORS's and
      proteasome inhibitors represents the most promising drugs that are being used in
      pediatric AML studies. 

PMID- 24113358
TI  - Cervical radiographical alignment: comprehensive assessment techniques and
      potential importance in cervical myelopathy.
AB  - STUDY DESIGN: Narrative review. OBJECTIVE: To provide a comprehensive narrative
      review of cervical alignment parameters, the methods for quantifying cervical
      alignment, normal cervical alignment values, and how alignment is associated with
      cervical deformity and myelopathy with discussions of health-related quality of
      life. SUMMARY OF BACKGROUND DATA: Indications for surgery to correct cervical
      alignment are not well-defined and there is no set standard to address the amount
      of correction to be achieved. In addition, classifications of cervical deformity
      have yet to be fully established and treatment options defined and clarified.
      METHODS: A survey of the cervical spine literature was conducted. RESULTS: New
      normative cervical alignment values from an asymptomatic volunteer population are
      introduced, updated methods for quantifying cervical alignment are discussed, and
      describing the relationship between cervical alignment, disability, and
      myelopathy are outlined. Specifically, methods used to quantify cervical
      alignment include cervical lordosis, cervical sagittal vertical axis, and
      horizontal gaze with the chin-brow vertical angle. Updated methods include T1
      slope. Evidence from a few recent studies suggests correlations between
      radiographical parameters in the cervical spine and health-related quality of
      life. Analysis of the cervical regional alignment with respect to overall spinal
      pelvic alignment is emerging and critical. Cervical myelopathy and sagittal
      alignment of the cervical spine are closely related as cervical deformity can
      lead to spinal cord compression and tension. CONCLUSION: Cervical deformity
      correction should take on a comprehensive approach in assessing global cervical
      pelvic relationships and the radiographical parameters that effect health-related
      quality of life scores are not well-defined. Cervical alignment may be important
      in assessment and treatment of cervical myelopathy. Future work should
      concentrate on correlation of cervical alignment parameters to disability scores
      and myelopathy outcomes. SUMMARY STATEMENTS: STATEMENT 1: Cervical sagittal
      alignment (cervical SVA and kyphosis) is related to thoracolumbar spinal pelvic
      alignment and to T1 slope. STATEMENT 2: When significant deformity is clinically
      or radiographically suspected, regional cervical and relative global spinal
      alignment should be evaluated preoperatively via standing 3-foot scoliosis X-rays
      for appropriate operative planning. STATEMENT 3: Cervical sagittal alignment (C2
      C7 SVA) is correlated to regional disability, general health scores and to
      myelopathy severity. STATEMENT 4: When performing decompressive surgery for CSM,
      consideration should be given to correction of cervical kyphosis and cervical
      sagittal imbalance (C2-C7 SVA) when present.

PMID- 24113359
TI  - Alternative procedures for the treatment of cervical spondylotic myelopathy:
      arthroplasty, oblique corpectomy, skip laminectomy: evaluation of comparative
      effectiveness and safety.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To perform an evidence synthesis of
      the literature assessing the efficacy of arthroplasty, oblique corpectomy without
      fusion, and skip laminectomy to treat symptomatic cervical spondylotic myelopathy
      (CSM). SUMMARY OF BACKGROUND DATA: Traditionally, patients with symptomatic
      cervical spinal cord compression due to degenerative disease have been treated
      with anterior or posterior approaches or both. Recent reports suggest that there
      are several nontraditional management strategies that merit attention. The
      anterior procedures include decompression and anterior reconstruction with an
      artificial disc and oblique corpectomy without fusion. A posterior option is
      decompression, using the skip laminectomy technique. METHODS: We conducted a
      systematic search in MEDLINE and the Cochrane Collaboration Library for
      literature published through October 15, 2012, on human studies published in the
      English language containing abstracts to answer the following key questions: (1)
      Is there evidence that artificial disc replacement after neural decompression
      results in equal or improved outcomes compared with anterior cervical
      decompression and fusion for CSM? (2) Describe the outcomes of oblique corpectomy
      without fusion for CSM? (3) Is there evidence that skip laminectomy results in
      equal or improved outcomes compared with laminoplasty for CSM? RESULTS: The
      initial literature search yielded 141 unique, potentially relevant citations,
      which were evaluated against the inclusion/exclusion criteria set a priori. A
      total of 10 studies were selected for inclusion. For question 1, 2 studies
      suggested that neurological outcomes favored artificial disc replacement compared
      with anterior cervical decompression and fusion, whereas functional and pain
      outcomes were inconsistently reported. For question 2, 5 reported case series
      suggested favorable neurological, functional, and pain outcomes associated with
      oblique corpectomy in subjects with CSM, compared with the pretreatment
      condition. For question 3, 3 studies comparing laminoplasty with skip laminectomy
      suggested similar neurological outcomes between treatment groups, although
      functional and pain outcomes were inconsistently reported. CONCLUSION: A paucity
      of high-quality literature exists regarding treatment outcomes associated with
      arthroplasty, oblique corpectomy without fusion, and skip laminectomy for
      symptomatic CSM. Comparative prospective studies with long-term follow-up and
      standardized outcome measures are needed to assess treatment outcomes associated
      with these alternative techniques appropriately. EVIDENCE-BASED CLINICAL
      RECOMMENDATIONS: RECOMMENDATION 1: No recommendation can be made from comparative
      literature regarding treatment outcomes comparing ADR with ACDF for CSM. OVERALL
      STRENGTH OF EVIDENCE: Insufficient. STRENGTH OF RECOMMENDATION: Strong.
      RECOMMENDATION 2: No recommendation can be made from comparative literature
      regarding treatment outcomes comparing laminoplasty with skip laminectomy for
      CSM. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH OF RECOMMENDATION: Strong.
      SUMMARY STATEMENTS: Oblique corpectomy is an option in selected cases of CSM. It
      should not be considered a first-line treatment strategy because of the
      relatively high morbidity associated with this procedure.

PMID- 24113360
TI  - Pathogen burden and hypertension: more questions than answers.

PMID- 24113361
TI  - Characterization and application of aminoamide-oxidizing enzyme from Aspergillus
      carbonarius AIU 205.
AB  - We isolated Aspergillus carbonarius AIU 205 as a new producer of an enzyme
      catalyzing oxidative deamination of 4-aminobutanamide (4-ABAD) to 4-oxobutanamide
      with the subsequent release of ammonia and hydrogen peroxide. Since the strain
      produced three enzymes with different Km values for 4-ABAD, the enzyme with
      lowest Km value (0.31 mM) was purified and revealed certain remarkable
      properties. The enzyme also oxidized aliphatic monoamines, aromatic amines and
      aliphatic aminoalcohols, but did not oxidize l-amino acids and aliphatic
      diamines. The Vmax/Km values for aliphatic monoamines were higher than that for 4
      ABAD, and the enzyme activity was strongly inhibited by inhibitors of copper
      containing amine oxidases. Thus, it was concluded that the enzyme might belong to
      a group of copper-containing amine oxidase. The 4-ABAD oxidase activity of this
      enzyme was optimum at pH 7.0, and the enzyme activity at pH 6.0 was 65% of that
      at pH 7.0. The enzyme was useful for increasing the sensitivity of l-lysine assay
      using l-amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813.

PMID- 24113362
TI  - Innate immunity in an in vitro murine blastocyst model using embryonic and
      trophoblast stem cells.
AB  - The immune system has two broad components-innate and adaptive immunity. Adaptive
      immunity becomes established only after the onset of hematopoiesis, whereas the
      innate immune system may be actively protecting organisms from microbial invasion
      much earlier in development. Here, we address the question of whether the innate
      immune system functions in the early-stage embryo, i.e., the blastocyst. The
      innate immune system was studied by using in vitro blastocyst models, e.g.,
      embryonic stem (ES) and trophoblast stem (TS) cell cultures. The expression of
      Toll-like receptors (TLR)-2, -3, and -5 could be detected in both ES and TS
      cells. The expression of interferon (IFN)-beta was induced by the addition of
      polyinosinic:polycytidylic acid [poly(I:C)] in TS cells, but not ES cells,
      although TLR-3 was expressed at the same level in both cell types. In turn, ES
      cells responded to IFN-beta exposure by expressing IFN-induced anti-viral genes,
      e.g., RNA-dependent protein kinase and 2', 5'-oligoadenylate synthetase (OAS).
      Neither a reduction in ES cell proliferation nor cell death in these cultures was
      observed after IFN-beta stimulation. Furthermore, OAS1a expression was induced in
      ES/TS co-cultures after poly(I:C) stimulation, but was not induced when either
      cell type was cultured alone. In conclusion, TS cells react to poly(I:C)
      stimulation by producing IFN-beta, which induces IFN-inducible genes in ES cells.
      This observation suggests that the trophectoderm, the outer layer of the
      blastocyst, may respond to viral infection, and then induce anti-viral gene
      expression via IFN-beta signaling to the blastocyst inner cell mass.

PMID- 24113363
TI  - Guanine binding to gold nanoparticles through nonbonding interactions.
AB  - Gold nanoparticles have been widely used as nanocarriers in gene delivery.
      However, the binding mechanism between gold nanoparticles and DNA bases remains a
      puzzle. We performed density functional theory calculations with and without
      dispersion correction on Au(N)( (N = 13, 55, or 147) nanoparticles in high
      symmetry cuboctahedral structures to understand the mechanism of their binding
      with guanine at the under-coordinated sites. Our study verified that: (i)
      negative charges transfer from the inner area to the surface of a nanoparticle as
      a result of the surface quantum trapping effect; and (ii) the valence states
      shift up toward the Fermi level, and thereby participate more actively in the
      binding to guanine. These effects are more prominent in a smaller nanoparticle,
      which has a larger surface-to-volume ratio. Additional fragment orbital analysis
      revealed that: (i) electron donation from the lone-pair orbital of N to the
      unoccupied orbital of the Au cluster occurs in all complexes; (ii) pi back
      donation occurs from the polarized Au d(yz) orbital to the N p(y)-pi* orbital
      when there is no Au...H-N hydrogen bond, and, (iii) depending on the
      configuration, Au...H-N hydrogen bonding can also exist, to which the Au occupied
      orbital and the H-N unoccupied orbital contribute.

PMID- 24113364
TI  - Synthesis and evaluation of (Z)-2,3-diphenylacrylonitrile analogs as anti-cancer
      and anti-microbial agents.
AB  - In the present study, a series of (Z)-2,3-diphenylacrylonitrile analogs were
      synthesized and then evaluated in terms of their cytotoxic activities against
      four human cancer cell lines, e.g. lung cancer (A549), ovarian cancer (SK-OV-3),
      skin cancer (SK-MEL-2), and colon cancer (HCT15), as well as anti-microbial
      activities against three microbes, e.g. Staphylococcus aureus, Salmonella typhi,
      and Aspergillus niger. The title compounds were synthesized by Knoevenagel
      condensation reaction of benzyl cyanide or p-nitrobenzyl cyanide with substituted
      benzaldehydes in good yields. Most of the compounds exhibited significant
      suppressive activities against the growth of all cancer cell lines. Compound 3c
      was most active in inhibiting the growth of A549, SK-OV-3, SK-MEL-2, and HCT15
      cells lines with IC50 values of 0.57, 0.14, 0.65, and 0.34 mg/mL, respectively,
      followed by compounds 3f, 3i, and 3h. Compound 3c exhibited 2.4 times greater
      cytotoxic activity against HCT15 cells, whereas it showed similar potency against
      SK-OV-3 cells to that of the standard anti-cancer agent doxorubicin. Structure
      activity relationship study revealed that electron-donating groups at the para
      position of phenyl ring B were more favorable for improved cytotoxic activity,
      whereas the presence of electron-withdrawing groups was unfavorable compare to
      unsubstituted acrylonitrile. An optimal electron density on phenyl ring A of (Z)
      2,3-diphenylacrylonitrile analogs was crucial for their cytotoxic activities
      against human cancer cell lines used in the present study. Qualitative structure
      cytotoxic activity relationships were studied using physicochemical parameters; a
      good correlation between calculated polar surface area (PSA), a lipophobic
      parameter, and cytotoxic activity was found. Moreover, all compounds showed
      significant anti-bacterial activities against S. typhi, whereas compound 3k
      showed potent inhibition against both S. aureus and S. typhi bacterial strains.

PMID- 24113365
TI  - Pyranoxanthones: Synthesis, growth inhibitory activity on human tumor cell lines
      and determination of their lipophilicity in two membrane models.
AB  - The benzopyran and dihydrobenzopyran moieties can be considered as "privileged
      motifs" in drug discovery being good platforms for the search of new bioactive
      compounds. These moieties are commonly found fused to the xanthonic scaffold
      belonging to the biologically important family of the generally designated
      prenylated xanthones. Several pyranoxanthones have shown promising antitumor
      activity and since most of them are from natural origin, the biosynthetic pathway
      only allows a particular pattern of substitution which limits their structural
      diversity and renders any broad structure-activity study hard to be established.
      Accordingly, with the aim of rationalizing the importance of the fused ring
      orientation and oxygenation pattern in pyranoxanthones, this study describes the
      synthesis of 14 new pyranoxanthones and evaluation of their cell growth
      inhibitory activity in four human tumor cell lines as well as their lipophilicity
      in two membrane models. This systematic approach allowed establishing structure
      activity and structure-lipophilicity relationships for the obtained compounds in
      combination with 6 previously described compounds. From this work an angular
      pyranoxanthone scaffold emerged as particularly promising, presenting a potent
      cell growth inhibitory activity and suitable drug-like lipophilicity. 

PMID- 24113366
TI  - Synthesis of novel benzo[4,5]thiazolo[1,2-a]pyrimidine-3-carboxylate derivatives
      and biological evaluation as potential anticancer agents.
AB  - A novel series of building blocks consisting of benzo[4,5]thiazolo[1,2
      a]pyrimidine-3-carboxylate have been synthesized as potential anticancer
      compounds. These compounds were prepared from 2-aminobenzothiazole, benzaldehyde
      and ethyl acetoacetate in ethylene glycol by catalysing with TBAHS to give
      benzo[4,5]thiazo[1,2-a]pyrimidine derivative 4 followed by the formation of amide
      by reaction with several secondary amines in good yields. The cytotoxicity of
      these compounds was evaluated against human cancer cell lines in vitro (A549,
      HeLa, MDA-MB-231 and MCF-7). Compound 5b exhibited promising cytotoxicity with
      IC50 values of 0.58 and 1.58 MUM specifically against human breast adenocarcinoma
      cell lines, MCF-7 and MDA-MB-231, while compound 5a showed promising cytotoxicity
      against MDA-MB-231 (IC50 value of 5.01 MUM).

PMID- 24113367
TI  - Prenatal exposure to selective serotonin reuptake inhibitors and childhood
      overweight at 7 years of age.
AB  - PURPOSE: To investigate a possible association between prenatal selective
      serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years
      of age. METHODS: Information on pregnancy exposures and prevalence of childhood
      overweight at 7 years of age was obtained from the Danish National Birth Cohort.
      Overweight was classified as body mass index >85th percentile, based on age and
      sex. Based on an a priori hypothesis, we conducted analyses stratified by child
      sex to examine sex-specific differences. RESULTS: Of eligible pregnant women, 127
      reported using an SSRI, 490 reported having a psychiatric illness but no
      psychotropic medication use, and 35,568 reported no psychiatric illness and no
      psychotropic medication use. In comparison to children of mothers with a
      psychiatric illness but no SSRI use during pregnancy, prenatal SSRI exposure
      overall was not associated with an increased risk of childhood overweight
      (adjusted prevalence ratio [aPR] 1.12; 95% confidence interval 0.71 to 1.77).
      However, when stratified according to child sex, an increased risk was observed
      among males (aPR 1.78; 95% CI, 1.01 to 3.12) but not females (aPR 0.86; 95% CI,
      0.37 to 1.99). In contrast, female children of mothers with a psychiatric illness
      but no SSRI use during pregnancy were more likely to be overweight than female
      children of unexposed mothers (aPR 1.45; 95% CI, 1.05 to 2.02). This association
      was not mirrored among males (aPR 1.06; 95% CI, 0.76 to 1.50). CONCLUSIONS: We
      observed the potential for opposing sex-specific differences in the long-term
      effects of prenatal exposure to SSRI use and/or maternal psychiatric illness on
      childhood overweight. Limitations of the present study suggest that further
      research in this area may be warranted with larger sample sizes and longer follow
      up.

PMID- 24113368
TI  - 5-Fluorouracil for epithelial downgrowth after Descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To report the use of intracameral 5-fluorouracil (5-FU) to treat
      epithelial downgrowth after performing a Descemet-stripping automated endothelial
      keratoplasty (DSAEK). METHODS: We describe the case of a 79-year-old woman who
      underwent a DSAEK for pseudophakic Fuchs endothelial corneal dystrophy. The
      patient required 2 repeat DSAEKs for graft failure and persistent, visually
      significant interface haze. Six months after the third and most recent DSAEK, the
      patient was followed up and found to have a visual acuity of 20/100. On
      examination, the patient continued to have a persistent interface haze. However,
      the patient also had a cellular anterior chamber reaction despite the
      administration of frequent topical corticosteroids, and subtle findings of a
      translucent, membranous growth over the iris. Argon laser photocoagulation of the
      area resulted in a whitening response, characteristic of epithelial growth.
      RESULTS: Epithelial downgrowth was diagnosed, and intracameral 5-FU was
      administered. One month after the injection was given, the patient's examination
      results and vision improved to 20/60. Six months after the single injection, the
      patient had a clear DSAEK graft without interface haze, a quiet chamber, and
      20/30 visual acuity. CONCLUSIONS: Epithelial downgrowth that occurs after
      performing a DSAEK can be treated successfully using intracameral 5-FU.

PMID- 24113369
TI  - Bimanual technique for insertion and positioning of endothelium-Descemet membrane
      graft in Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To describe a new bimanual technique for insertion and positioning of
      endothelium-Descemet membrane (EDM) grafts in Descemet membrane endothelial
      keratoplasty (DMEK). METHODS: Prospective, noncomparative, consecutive
      interventional case series, including 15 pseudophakic eyes of 15 patients treated
      with DMEK at the Instituto de Microcirugia Ocular, Barcelona, Spain. A bimanual
      infusion technique was used to introduce and position donor's EDM. Partial
      tamponade was achieved with 20% sulfur hexafluoride (SF6). Intraocular
      manipulation time of EDM grafts, rebubbling rate, and endothelial cell density
      were evaluated. RESULTS: Six months postoperatively, mean uncorrected visual
      acuity and best spectacle-corrected visual acuity (BSCVA) improved from 20/100 to
      20/50 and from 20/80 to 20/25, respectively (P < 0.001). Six eyes (40%) had >=
      20/20 BSCVA, and 13 (86%) eyes had >= 20/30 BSCVA. Mean donor cell density
      decreased from 2690 +/- 302 to 1998 +/- 621 cells per square millimeter,
      representing a mean cell loss of 26% +/- 20%. EDM was stripped successfully in
      all cases. Mean intraocular manipulation time of donor's EDM (interval between
      main incision closure and final EDM positioning) was 4.10 +/- 0.5 minutes.
      Intracameral air reinjection was needed in 1 case (6.6%) with a partial
      peripheral graft detachment. No episodes of immunologic graft rejection were
      documented. CONCLUSIONS: Insertion and positioning of EDM grafts in DMEK was
      successfully achieved using this bimanual infusion technique and 20% SF6 partial
      tamponade, with a low intraocular manipulation time and very low postoperative
      rebubbling rates, regardless of the preservation method and the donor's age.
      However, prospective comparative studies are required to demonstrate the long
      term safety compared with other approaches.

PMID- 24113370
TI  - Individual phenotypic variances in a family with Thiel-Behnke corneal dystrophy.

PMID- 24113371
TI  - Corneal keloid: report of natural history and outcome of surgical management in
      two cases.
AB  - PURPOSE: To report the natural history and the outcome after the surgical
      management of 2 cases of corneal keloids. METHODS: Two male patients, 21 and 24
      years old, with a history of corneal opacity for 5 and 17 years, respectively,
      with no history of an ocular trauma were studied. RESULTS: The first patient
      initially underwent a superficial keratectomy (SK), after which the corneal
      opacification recurred. He subsequently underwent 2 SK procedures combined with
      phototherapeutic keratectomy and mitomycin C, followed by a femtosecond laser
      assisted deep anterior lamellar keratoplasty. The second patient underwent a
      bilateral SK followed by a penetrating keratoplasty in the left eye with the
      rapid recurrence of the lesion. The patient subsequently underwent an
      implantation of a Boston type 1 keratoprosthesis in the right eye, with a
      favorable outcome. The histopathologic features of both excised corneal specimens
      were consistent with the diagnosis of a corneal keloid. CONCLUSIONS: Corneal
      keloids recur after SK and phototherapeutic keratectomy, indicating that
      keratoplasty procedures may be more effective than keratectomy procedures in
      their management. However, corneal keloids may recur even after a penetrating
      keratoplasty, in which case keratoprosthesis implantation represents a viable
      option for visual rehabilitation.

PMID- 24113372
TI  - Changes in rabbit corneal innervation induced by the topical application of
      benzalkonium chloride.
AB  - PURPOSE: To investigate the effect of benzalkonium chloride (BAK) on corneal
      nerves. METHODS: Fifty-four adult New Zealand Albino rabbits were randomly
      divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was
      applied once daily to 1 eye of each rabbit for 9 days. The contralateral
      untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous
      tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining
      scores were compared with those of control values on days 3, 6, and 9. Corneal
      whole mounts were immunostained with a specific antitubulin betaIII antibody to
      label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal
      nerve fiber densities were quantified. The structure of the central cornea was
      examined by means of in vivo confocal microscopy on day 9. RESULTS: The topical
      application of BAK resulted in lower corneal sensitivity and higher Rose Bengal
      staining scores on day 3, whereas there were no significant changes in the BUT,
      Schirmer, and corneal fluorescein scores. Decreased nerve densities in
      superficial and subbasal layers were observed in BAK-treated eyes on days 3 and
      6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced
      Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein
      staining scores on day 9. Corneal superficial epithelial cell size was
      significantly larger in all BAK-treated eyes compared with that in control eyes.
      CONCLUSIONS: The topical application of BAK can quickly cause corneal
      hypoesthesia without tear deficiency. Changes in corneal innervation
      significantly correlate with BAK-induced ocular surface changes.

PMID- 24113373
TI  - Depth dependence of the single chamber response function of the I'mRT MatriXX
      array in a 6 MV photon beam.
AB  - One of the factors which influence the spatial resolution of a 2D detector array
      is the size of the single detector, another the transport of the secondary
      electrons from the walls into the measuring volume. In this study, the single ion
      chamber dose response function of an I'mRT MatriXX array was determined by
      comparison between slit beam dose profiles measured with the array and with EBT2
      radiochromic film in a solid water-equivalent phantom at a shallow depth of 0.5cm
      and at a depth of 5cm beyond the depth dose maximum for a 6 MV photon beam. The
      dose response functions were obtained using two methods, the best fit method and
      the deconvolution method. At the shallow depth, a Lorentz function and at 5cm
      depth a Gaussian function, both with the same FWHM of 7.4mm within limits of
      uncertainty, were identified as the best suited dose response functions of the
      4.5mm diameter single array chamber. These dose response functions were then
      tested on various dose profiles whose true shape had been determined with EBT2
      film and with the IC03 ionization chamber. By convolving these with the Lorentz
      kernel (at shallow depth) and the Gaussian kernel (at 5cm depth) the signal
      profiles measured with the I'mRT MatriXX array were closely approximated. Thus,
      the convolution of TPS-calculated dose profiles with these dose response
      functions can minimize the differences between calculation and measurement which
      occur due to the limited spatial resolution of the I'mRT MatriXX detector. 

PMID- 24113374
TI  - Deflectometric analysis of high volume injection molds for production of
      occupational eye wear.
AB  - PURPOSE: Most of the protective eye wear devices currently on the market are
      manufactured on simple polycarbonate shields, produced by injection molding
      techniques. Despite high importance of optical quality, injection molds are
      rarely inspected for surface quality before or during the manufacturing process.
      Quality degradation is mainly monitored by optical testing of the molded parts.
      The purpose of this work was to validate a non-contact deflectometric measurement
      technique for surface and shape analysis of injection molds to facilitate
      deterministic surface quality control and to monitor minor conformity of the
      injection mold with the design data. MATERIAL AND METHODS: The system is based on
      phase-measuring deflectometry with a operating measurement field of 80*80 mm(2)
      (+/-18 degrees  slope), a lateral resolution of 60MUm and a local sensitivity of
      some nanometers. The calibration was tested with a calibration normal and a
      reference sphere. The results were crosschecked against a measurement of the same
      object with a tactile coordinate measuring machine. Eight injection molds for
      production of safety goggles with radii of +58mm (convex) and -60mm (concave)
      were measured in this study. The molds were separated into two groups (cavity 1
      and 2 of the tool with different polishing techniques) and measured to test
      whether the measurement tool could extract differences. The analysis was
      performed on difference height between the measured surface and the spherical
      model. RESULTS: The device could derive the surface change due to polishing and
      discriminate between both polishing techniques, on the basis of the measured
      data. The concave nozzle sides of the first group (cavity 1) showed good shape
      conformity. In comparison, the nozzle sides of the second group (cavity 2) showed
      local deviations from design data up to 14.4MUm. Local form variations of about
      5MUm occurred in the field of view. All convex ejector sides of both groups
      (cavity 1 and 2) showed rotational symmetric errors and the molds were measured
      in general flatter than design data. CONCLUSION: We applied a deflectometric
      system for measuring and evaluating specular reflective injection molding tools
      to optimize the production process of occupational eye wear. The surface quality
      could be inline monitored in the production processes for actual spectacle
      models.

PMID- 24113375
TI  - Effects of quantum noise in 4D-CT on deformable image registration and derived
      ventilation data.
AB  - Quantum noise is common in CT images and is a persistent problem in accurate
      ventilation imaging using 4D-CT and deformable image registration (DIR). This
      study focuses on the effects of noise in 4D-CT on DIR and thereby derived
      ventilation data. A total of six sets of 4D-CT data with landmarks delineated in
      different phases, called point-validated pixel-based breathing thorax models
      (POPI), were used in this study. The DIR algorithms, including diffeomorphic
      morphons (DM), diffeomorphic demons (DD), optical flow and B-spline, were used to
      register the inspiration phase to the expiration phase. The DIR deformation
      matrices (DIRDM) were used to map the landmarks. Target registration errors (TRE)
      were calculated as the distance errors between the delineated and the mapped
      landmarks. Noise of Gaussian distribution with different standard deviations
      (SD), from 0 to 200 Hounsfield Units (HU) in amplitude, was added to the POPI
      models to simulate different levels of quantum noise. Ventilation data were
      calculated using the DeltaV algorithm which calculates the volume change
      geometrically based on the DIRDM. The ventilation images with different added
      noise levels were compared using Dice similarity coefficient (DSC). The root mean
      square (RMS) values of the landmark TRE over the six POPI models for the four DIR
      algorithms were stable when the noise level was low (SD <150 HU) and increased
      with added noise when the level is higher. The most accurate DIR was DD with a
      mean RMS of 1.5 +/- 0.5 mm with no added noise and 1.8 +/- 0.5 mm with noise (SD
      = 200 HU). The DSC values between the ventilation images with and without added
      noise decreased with the noise level, even when the noise level was relatively
      low. The DIR algorithm most robust with respect to noise was DM, with mean DSC =
      0.89 +/- 0.01 and 0.66 +/- 0.02 for the top 50% ventilation volumes, as compared
      between 0 added noise and SD = 30 and 200 HU, respectively. Although the landmark
      TRE were stable with low noise, the differences between ventilation images
      increased with noise level, even when the noise was low, indicating ventilation
      imaging from 4D-CT was sensitive to image noise. Therefore, high quality 4D-CT is
      essential for accurate ventilation images. 

PMID- 24113377
TI  - Lysophosphatidic acid induces reactive oxygen species generation by activating
      protein kinase C in PC-3 human prostate cancer cells.
AB  - Prostate cancer is one of the most frequently diagnosed cancers in males, and PC
      3 is a cell model popularly used for investigating the behavior of late stage
      prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates
      multiple behaviors in cancer cells, such as proliferation, migration and
      adhesion. We have previously demonstrated that LPA enhances vascular endothelial
      growth factor (VEGF)-C expression in PC-3 cells by activating the generation of
      reactive oxygen species (ROS), which is known to be an important mediator in
      cancer progression. Using flow cytometry, we showed that LPA triggers ROS
      generation within 10min and that the generated ROS can be suppressed by
      pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In
      addition, transfection with LPA1 and LPA3 siRNA efficiently blocked LPA-induced
      ROS production, suggesting that both receptors are involved in this pathway.
      Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C
      (PKC) were also suggested to participate in LPA-induced ROS generation. Overall,
      we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and
      this is mediated through the PLC/PKC/Nox pathway. 

PMID- 24113378
TI  - Biliverdin reductase plays a crucial role in hypoxia-induced chemoresistance in
      human glioblastoma.
AB  - Hypoxia-induced alterations in the cellular redox status play a critical role in
      the development of hypoxia-induced chemoresistance in cancer cells. Human
      biliverdin reductase (hBVR), an enzyme involved in the conversion of biliverdin
      into bilirubin in heme metabolism, was recently identified as an important
      cytoprotectant against oxidative stress and hypoxia. However, the role of hBVR on
      hypoxia-induced drug resistance has not been previously investigated. Using human
      glioblastoma cell lines, we evaluated the potential role of hBVR in hypoxia
      induced drug resistance. We found that hypoxia caused a significant increase in
      hBVR expression in glioblastoma cells that was accompanied by chemoresistance. We
      also observed that siRNA-based targeting of hBVR genes attenuated the hypoxia
      induced chemoresistance. Furthermore, knocking down hBVR induced a marked
      increase in the levels of intracellular reactive oxygen species under hypoxic
      conditions, and the chemosensitizing effect of hBVR depletion was reversed by
      pretreatment with the antioxidant N-acetylcysteine. These findings suggest that
      hBVR significantly contributes to the modulation of hypoxia-induced
      chemoresistance of glioblastoma cells by adjusting their cellular redox status. 

PMID- 24113379
TI  - Nspc1 regulates the key pluripotent Oct4-Nanog-Sox2 axis in P19 embryonal
      carcinoma cells via directly activating Oct4.
AB  - Nspc1 is an identified transcription repressor. However, transiently up-regulated
      or down-regulated Nspc1 in P19 embryonal carcinoma cells affects expression
      levels of Oct4, Sox2 and Nanog in a positive correlation. Luciferase activity
      assays verified that Nspc1 regulates the Oct4 promoter in a dose dependent
      manner. ChIP assay shows that Nspc1 activates Oct4 by directly binding to the (
      1021 to -784) region of Oct4 promoter. Dominant negative analysis indicated the
      activation is dependent on the retinoid acid response element (RARE). We
      demonstrated Nspc1 has a positive role in maintaining the pluripotency of P19
      cells by directly regulating Oct4. 

PMID- 24113376
TI  - A lipidomic perspective on inflammatory macrophage eicosanoid signaling.
AB  - Macrophages are central to essential physiological processes including the
      regulation of innate and adaptive immunity, but they are also central to a number
      of inflammatory disease states. These immune cells also possess remarkable
      plasticity and display various shades of functionalities based on changes in the
      surrounding molecular environment. Macrophage biology has defined various
      phenotypes and roles in inflammation based primarily on cytokine and chemokine
      profiles of cells in different activation states. Importantly, macrophages are
      elite producers of eicosanoids and other related lipid mediators during
      inflammation, but specific roles of these molecules have not generally been
      incorporated into the larger context of macrophage biology. In this review, we
      discuss the current classification of macrophage types and their roles in
      inflammation and disease, along with the practical challenges of studying
      biologically relevant phenotypes ex vivo. Using the latest advances in eicosanoid
      lipidomics, we highlight several key studies from our laboratory that provide a
      comprehensive understanding of how eicosanoid metabolism differs between
      macrophage phenotypes, along with how this metabolism is altered by changes in
      membrane fatty acid distribution and varied durations of Toll-like receptor (TLR)
      priming. In conclusion, we summarize several examples of the benefit of
      macrophage plasticity to develop accurate cellular mechanisms of lipid
      metabolism, and insights from lipidomic analyses about the differences in
      eicosanoid pathway enzyme activity in vitro vs. in cells ex vivo. Examples of new
      techniques to further understand the role of macrophage eicosanoid signaling in
      vivo are also discussed. 

PMID- 24113380
TI  - Different phosphorylation rates among vertebrate cone visual pigments with
      different spectral sensitivities.
AB  - Cone photoreceptor subtypes having different spectral sensitivities exhibit
      different recovery kinetics in their photoresponses in some vertebrates.
      Phosphorylation by G protein-coupled receptor kinase (GRK) is essential for the
      rapid inactivation of light-activated visual pigment, which is the rate-limiting
      step of the cone photoresponse recovery in salamander. In this study we compared
      the rate of light-dependent phosphorylation by GRK7 of carp green- and blue
      sensitive cone visual pigments. Blue pigment was phosphorylated significantly
      less effectively than green pigment, suggesting that the difference in the
      pigment phosphorylation rate is responsible for the difference in photoresponse
      kinetics among cone photoreceptor subtypes. 

PMID- 24113381
TI  - GRP78 secreted by tumor cells stimulates differentiation of bone marrow
      mesenchymal stem cells to cancer-associated fibroblasts.
AB  - Cancer-associated fibroblasts (CAFs), one type of tumor-associated stromal cells,
      have been shown to provide a favorable environment for the malignant tumor
      progression. Extensive reports have demonstrated that mesenchymal stem cells
      (MSCs) can function as precursors for CAFs. However, the mechanisms by which
      tumor cells induce the transition of MSCs to CAFs have not been well established.
      GRP78, traditionally known as an endoplasmic reticulum (ER) chaperone, has been
      identified to overexpress in a variety of tumor entities and be involved in
      promoting survival and chemoresistance of tumor cells. Here, we interrogated the
      role of GRP78 in the generation of CAFs from MSCs. The results showed that GRP78
      treatment induced expression of alpha-smooth muscle actin (alpha-SMA), a marker
      for CAFs, in human bone marrow mesenchymal stem cells (HBMSCs) as well as murine
      bone marrow mesenchymal stem cells (BMMSCs). This phenomenon was correlated with
      the stimulated phosphorylation of Smad2/3. Furthermore, the GRP78-induced alpha
      SMA expression in HBMSCs was obviously attenuated by SB431542, a TGF-beta type I
      receptor kinase inhibitor. Taken together, the present data suggested that tumor
      derived secreted GRP78 elicited the differentiation of bone marrow-derived
      mesenchymal stem cells (BMSCs) to CAFs through activating TGF-beta/Smad signaling
      pathway, which may represent a novel mechanism for transition of BMSCs to CAFs
      and a hitherto unknown function of GRP78 in the tumor microenvironment. 

PMID- 24113383
TI  - Lipopolysaccharide-induced multinuclear cells: increased internalization of
      polystyrene beads and possible signals for cell fusion.
AB  - A murine macrophage-derived line, RAW264.7, becomes multinuclear on stimulation
      with lipopolysaccharide (LPS), an outer membrane component of Gram-negative
      bacteria. These multinuclear cells internalized more polystyrene beads than
      mononuclear cells or osteoclasts (Nakanishi-Matsui, M., Yano, S., Matsumoto, N.,
      and Futai, M., 2012). In this study, we analyzed the time courses of cell fusion
      in the presence of large beads. They were internalized into cells actively fusing
      to become multinuclear. However, the multinuclear cells once formed showed only
      low phagocytosis activity. These results suggest that formation of the
      multinuclear cells and bead internalization took place simultaneously. The
      formation of multinuclear cells was blocked by inhibitors for phosphoinositide 3
      kinase, phospholipase C, calcineurin, and c-Jun N-terminal kinase. In addition,
      interleukin 6 and 10 also exhibited inhibitory effects. These signaling molecules
      and cytokines may play a crucial role in the LPS-induced multinuclear cell
      formation. 

PMID- 24113382
TI  - Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA
      synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous
      fatty acids.
AB  - In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members
      of a highly conserved family of proteins, which function in fatty acid transport
      proceeding through vectorial acylation and in the activation of very long chain
      fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4,
      for example directly function in fatty acid transport and very long chain fatty
      acids activation while FATP5 does not function in fatty acid transport but
      activates secondary bile acids. In the present work, we have used stable
      isotopically labeled fatty acids differing in carbon length and saturation in
      cells expressing FATP2 to gain further insights into how this protein functions
      in fatty acid transport and intracellular fatty acid trafficking. Our previous
      studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA
      and significantly increased C18:3-CoA and C22:6-CoA after 4h. The increases in
      C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain
      acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial
      acylation. The very long chain acyl CoA synthetase activity of FATP2 is
      consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport
      from their respective exogenous fatty acids. The trafficking of exogenous fatty
      acids into phosphatidic acid (PA) and into the major classes of phospholipids
      (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol
      (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed
      with the expression of FATP2. The trafficking of exogenous C16:0 and C22:6 into
      PA was significant where there was 6.9- and 5.3-fold increased incorporation,
      respectively, over the control; C18:3 and C20:4 also trended to increase in the
      PA pool while there were no changes for C18:1 and C18:2. The trafficking of C18:3
      into PC and PI trended higher and approached significance. In the case of C20:4,
      expression of FATP2 resulted in increases in all four classes of phospholipid,
      indicating little selectivity. In the case of C22:6, there were significant
      increases of this exogenous fatty acids being trafficking into PC and PI.
      Collectively, these data support the conclusion that FATP2 has a dual function in
      the pathways linking the transport and activation of exogenous fatty acids. We
      discuss the differential roles of FATP2 and its role in both fatty acid transport
      and fatty acid activation in the context of lipid homeostasis. 

PMID- 24113384
TI  - Effects of professional support on nausea, vomiting, and quality of life during
      early pregnancy.
AB  - The purpose of this study was to examine the effectiveness of a professional
      support (PS) intervention (including individualized health education and
      supportive phone calls) in reducing the severity of nausea and vomiting (NV) and
      improving the quality of life (QOL) of women in early pregnancy. An experimental
      pretest/posttest design with a control group was used. Participants were
      recruited from a regional teaching hospital in southern Taiwan. The women in the
      experimental group (n = 40) received the PS intervention, while those in the
      control group (n = 39) only received routine nursing care. Analysis of covariance
      and mixed models were used to compare the experimental and control groups while
      adjusting for covariates. The severity of NV and the perceived level of symptom
      distress were significantly lower in the experimental group than in the control
      group during weeks 2 and 4, and the women in the experimental group showed a
      significant improvement in their QOL in week 4 (p < .05). However, there was no
      significant difference between the two groups in body weight at week 4 (p =
      .501). These findings provide empirical evidence in support of the effectiveness
      of PS in reducing the severity of NV and improving QOL for women during early
      pregnancy. This intervention could be routinely applied in prenatal nursing
      health education. Future studies could apply the concept of PS to different
      populations and health issues. 

PMID- 24113385
TI  - Self-organized noise resistance of oscillatory neural networks with spike timing
      dependent plasticity.
AB  - Intuitively one might expect independent noise to be a powerful tool for
      desynchronizing a population of synchronized neurons. We here show that,
      intriguingly, for oscillatory neural populations with adaptive synaptic weights
      governed by spike timing-dependent plasticity (STDP) the opposite is true. We
      found that the mean synaptic coupling in such systems increases dynamically in
      response to the increase of the noise intensity, and there is an optimal noise
      level, where the amount of synaptic coupling gets maximal in a resonance-like
      manner as found for the stochastic or coherence resonances, although the
      mechanism in our case is different. This constitutes a noise-induced self
      organization of the synaptic connectivity, which effectively counteracts the
      desynchronizing impact of independent noise over a wide range of the noise
      intensity. Given the attempts to counteract neural synchrony underlying tinnitus
      with noisers and maskers, our results may be of clinical relevance. 

PMID- 24113387
TI  - Prediction and characterization of protein-protein interaction network in
      Xanthomonas oryzae pv. oryzae PXO99 A.
AB  - Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight disease
      in rice, is one of the most serious plant pathogens worldwide. In the current
      analysis, we constructed a protein-protein interaction network of Xoo strain
      PXO99(A) with two computational approaches (interolog method and domain
      combination method), and verified by K-Nearest Neighbors classification method.
      The predicted PPI network of Xoo PXO99(A) contains 36,886 interactions among 1988
      proteins. KNN verification and GO annotation confirm the reliability of the
      network. Detailed analysis of flagellar synthesis and chemotaxis system shows
      that sigma factors (especially sigma(28), sigma(54)) in Xoo PXO99(A) are very
      important for flagellar synthesis and motility, and transcription factors RpoA,
      RpoB and RpoC are hubs to connect most sigma factors. Furthermore, Xoo PXO99(A)
      may have both cAMP and c-di-GMP signal transduction system, and the latter is
      especially important for this plant pathogen. This study therefore provides
      valuable clues to explore the pathogenicity and metabolic regulation of Xoo
      PXO99(A). 

PMID- 24113386
TI  - NADPH oxidase subunit p22(phox)-mediated reactive oxygen species contribute to
      angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in
      prostate cancer.
AB  - Excessive generation of reactive oxygen species (ROS) in cancer cells is
      associated with cancer development, but the underlying mechanisms and therapeutic
      significance remain elusive. In this study, we reported that levels of ROS and
      p22(phox) expression are greatly increased in human prostate cancer tissues, and
      knockdown of p22(phox) by specific small interfering RNA (siRNA) decreased ROS
      levels in prostate cancer cells. We also showed that stable downregulation of
      p22(phox) in prostate cancer cells inhibited cell proliferation and colony
      formation, which was mediated by AKT and extracellular signal-regulated kinase
      (ERK)1/2 signaling pathways and their downstream molecules hypoxia-inducible
      factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). The
      NADPH oxidase subunit NOX1 was also elevated in prostate cancer cells, and was
      involved in activation of AKT/ERK/HIF-1/VEGF pathway and regulation of cell
      proliferation. Knockdown of p22(phox) resulted in inhibition of tumor
      angiogenesis and tumor growth in nude mice. These findings reveal a new function
      of p22(phox) in tumor angiogenesis and tumor growth, and suggest that p22(phox)
      is a potential novel target for prostate cancer treatment. 

PMID- 24113388
TI  - Pre-chiasmatic transection of the optic nerve can save contralateral vision in
      patients with optic nerve sheath meningioms.
AB  - OBJECTIVES: With respect to its characteristic pattern of growth from the orbit
      into the intracranial space toward the chiasm, patients with optic nerve sheath
      meningiomas (ONSM) are threatened to loose function of both optic nerves.
      Fortunately, in less than 5% both optic nerves are involved initially. Hence,
      prevention of vision of the contralateral eye is the foremost aim of any therapy.
      Performing pre-chiasmatic transection might offer a further treatment option to
      avoid further tumor growth toward the chiasm. PATIENTS AND METHODS: In this
      retrospective study 12 patients with ONSM and blindness of the affected eye were
      included. The surgical approach was performed either from pterional intradural or
      as a combined approach from pterional extra- and intradural. RESULTS: Without any
      exceptions, vision of the contralateral eye could be preserved and did not show
      any deterioration after surgery or during the follow-up time of 50.6 months.
      Furthermore in 58.3% of patients gross total tumor resection could be achieved.
      During follow up observation in 67% of patients no further tumor progress or
      recurrences could be observed. 4 patients, however, showed delayed tumor progress
      or recurrences that were treated by radiotherapy. CONCLUSION: Pre-chiasmatic
      transection of the optic nerve might offer a surgical treatment option to control
      tumor growth and to preserve vision of the contralateral eye.

PMID- 24113389
TI  - Spin fluctuations and pairing symmetry in AxFe2-ySe2: dual effect of the
      itinerant and the localized nature of electrons.
AB  - We investigate the spin fluctuations and the pairing symmetry in AxFe2-ySe2 by
      the fluctuation exchange approximation. Besides the on-site interactions, the
      next-nearest-neighbor antiferromagnetic coupling J2 is also included. We find
      that both the itinerant and the localized natures of electrons are important to
      describe recent experimental results on the spin fluctuations and the pairing
      symmetry. In particular, a small J2 coupling can change the pairing gap from the
      d-wave symmetry to the extended s-wave symmetry. We have also studied the real
      space structures of the gap functions for different orbits in order to gain more
      insight into the nature of the pairing mechanism. 

PMID- 24113390
TI  - [Are temporary vena cava filters becoming permanent?].

PMID- 24113391
TI  - [Duplex ultrasound detection of type II endoleaks by after endovascular aneurysm
      repair: interest of contrast enhancement].
AB  - OBJECTIVE: Type II endoleaks (EFII) are related to retrograde flow via aorta
      tributaries. They are the most frequent complication after endovascular aneurysm
      repair (EVAR). We hypothesized that the use of contrast-enhanced ultrasound
      (CEUS) by an experienced vascular physician could increase the sensitivity of
      detecting EFII compared with computed tomography angiography (CTA) taken as the
      gold standard. MATERIAL AND METHOD: From November 2010 to February 2013, patients
      with EVAR were included prospectively. All patients had a color duplex ultrasound
      (CDU), CEUS and CTA. Sensitivity, specificity and kappa's coefficient were
      determined to estimate the performance of CDU and CEUS to assess EFII compared
      with CTA. RESULTS: Sixty CDU and 60 CEUS explorations were compared to 60 CTA
      explorations. Nineteen type EFII were detected by CTA, 14 by CDU and 15 by CEUS.
      CDU sensitivity was 74% (kappa=0.75), and CEUS sensitivity was 78% (kappa=0.8).
      Both tests exhibited 97% specificity. There was good agreement between CDU
      results (kappa=0.75) and CEUS results (kappa=0.8) compared with CTA. There was
      very good agreement between CDU and CEUS results for detection of EFII
      (kappa=0.93). There was no statistically significant difference between the
      sensitivity of CDU and CEUS (P=0.32). CONCLUSION: Our results suggest that
      contrast enhancement does not increase yield for ultrasound detection of type II
      endoleaks when performed by an experienced vascular physician.

PMID- 24113392
TI  - CH2OO Criegee biradical yields following photolysis of CH2I2 in O2.
AB  - Yields of CH2OO and CH2IO2 from the reaction of CH2I radicals with O2 are
      reported as a function of total pressure, [N2] and [O2] at T = 295 K using three
      complementary methods. Results from the three methods are similar, with no
      observed additional dependence on [O2]. The CH2I + O2 reaction has a yield of
      ~18% CH2OO at atmospheric pressure.

PMID- 24113393
TI  - Morphology of the abdominal muscles in ballet dancers with and without low back
      pain: a magnetic resonance imaging study.
AB  - OBJECTIVES: To evaluate the morphology of transversus abdominis and obliquus
      internus abdominis muscles and the ability to "draw in" the abdominal wall, in
      professional ballet dancers without low back pain, with low back pain or both hip
      region and low back pain. DESIGN: Observational study. METHODS: Magnetic
      resonance images of 31 dancers were taken at rest and during voluntary abdominal
      muscle contraction. Measurements included the thickness of transversus abdominis
      and obliquus internus abdominis muscles, lateral slide of the anterior extent of
      the transversus abdominis muscles (transversus abdominis slide) and reduction in
      total cross sectional area of the trunk. RESULTS: The transversus abdominis and
      obliquus internus abdominis muscles were thicker in male dancers and the right
      side was thicker than the left in both genders. There was no difference in muscle
      thickness as a proportion of the total thickness, between dancers with and
      without pain, although there was a trend for female dancers with low back pain
      only to have a smaller change in transversus abdominis muscle thickness with
      contraction than those without pain. Transversus abdominis slide was less in
      female dancers than in male dancers. When gender was ignored, the extent of
      transversus abdominis slide was less in dancers with low back pain only.
      Reduction in trunk cross sectional area with contraction was not different
      between genders or groups. CONCLUSIONS: This study provides evidence that the
      abdominal muscles (transversus abdominis and obliquus internus abdominis) are
      asymmetrical in dancers and although the abdominal muscles are not different in
      structure (resting thickness) in dancers with LBP, there is preliminary evidence
      for the behavioural change of reduced slide of transversus abdominis during the
      'draw in' of the abdominal wall.

PMID- 24113394
TI  - Ceramides are associated with inflammatory processes in human mediastinal adipose
      tissue.
AB  - BACKGROUND AND AIM: Ceramides are poorly characterized in human adipose tissue.
      The aim of this study was to investigate concentrations of different ceramide
      species in human subcutaneous and visceral adipose tissue depots and to determine
      associations between ceramides and global gene expression profiles. METHODS AND
      RESULTS: Concentrations of six ceramide species were determined in plasma and in
      subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4
      +/- 4.9 kg/m(2)). In the adipose tissue biopsies gene expression arrays were
      performed and relationships between ceramides and gene expression analyzed.
      Immunostaining of the two adipose tissue depots was performed in an independent
      group of 10 patients. Mediastinal adipose tissue contained significantly higher
      concentrations (p < 0.05) of all six ceramide species than the subcutaneous
      depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0
      and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding
      species in mediastinal adipose tissue, but there were no significant correlations
      between ceramides in plasma and subcutaneous adipose tissue. Multivariate
      analysis identified significant correlations between the total ceramide
      concentration and global gene expression within mediastinal, but not subcutaneous
      adipose tissue, according to cross-validation. Gene ontology analysis of genes
      related to ceramides in the mediastinal depot revealed that genes positively
      correlated with ceramides were associated mainly with immune and inflammatory
      categories, while genes negatively correlated with ceramides were associated
      mainly with lipid and carbohydrate metabolism. CONCLUSIONS: Ceramides in human
      mediastinal adipose tissue may be involved in inflammation and lipid and
      carbohydrate metabolism.

PMID- 24113395
TI  - Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub
      Saharan Africa.
AB  - OBJECTIVE: To describe immunologic, virologic, and clinical HIV disease
      progression by HIV-1 subtype among Africans with well documented estimated dates
      of HIV infection (EDIs). DESIGN: Prospective cohort. METHODS: Adults and youth
      with documented HIV-1 infection in the past 12 months were recruited from
      seroincidence cohorts in East and Southern Africa and followed at 3-6 month
      intervals. Blood for lymphocyte subset and viral load determination was collected
      at each visit. Pol was sequenced from the first positive specimen to ascertain
      subtype. Preantiretroviral therapy disease progression was measured by three time
      to-event endpoints: CD4 cell count 350 cells/MUl or less, viral load measurement
      at least 1 * 10 copies/ml, and clinical AIDS. RESULTS: From 2006 to 2011, 615
      participants were enrolled at nine research centers in Kenya, Rwanda, South
      Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed.
      Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%).
      After adjustment for age, sex, and human leukocyte antigen alleles in Cox
      regression analyses, subtype C-infected participants progressed faster than
      subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence
      interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and
      AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants
      reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and
      progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93,
      95% CI 1.21, 3.09). CONCLUSION: Subtype-specific differences in HIV disease
      progression suggest that the local subtype distribution be considered when
      planning HIV programs and designing and defining clinical endpoints for HIV
      prevention trials.

PMID- 24113397
TI  - Neonatal isolated rectal bleeding and the risk of hypersensitivity syndromes.
AB  - OBJECTIVE: When rectal bleeding occurs in an otherwise asymptomatic child, it can
      be classified as isolated rectal bleeding (IRB). Among the different etiologies
      suggested for IRB, one of the most common is a hypersensitivity reaction of the
      bowel mucosa to digested antigens. The objective of this study was to assess the
      long-term outcomes and the risk of developing hypersensitivity syndromes among
      infants following an IRB event. STUDY DESIGN: A historical prospective
      comparative study was carried out. The study compared 77 infants who were born at
      the Sheba Medical Center in Israel during the period 2002 to 2009 and who
      experienced a neonatal IRB event to 77 infants with the same gestational age, but
      without IRB. Data were obtained from hospital records and from phone interviews
      with the parents regarding hypersensitivity syndrome between the ages of 3 and 10
      years. RESULT: The IRB group was not at an increased risk of developing a
      hypersensitivity syndrome or gastrointestinal symptoms compared to the control
      group. Longer duration of breast-feeding was found to be related to a lower
      incidence of hypersensitivity symptoms. CONCLUSION: An IRB event in the neonatal
      period does not increase the risk of developing hypersensitivity syndromes or
      food allergies during childhood.

PMID- 24113398
TI  - Measurement of tritium in the free water of milk : spotting and quantifying some
      biases and proposing ways of improvement.
AB  - As one of the three natural isotopes of hydrogen, tritium is ubiquitous and may
      potentially be present in any water or organic molecule that constitutes a
      biological matrix. Milk is one of the most frequently monitored foodstuffs in the
      vicinity of chronic release of radionuclides, as it is a very common food product
      and also because it integrates deposition on large areas of grass or crops at a
      local scale. Different parameters have been studied to assess their impact on the
      reliability of tritium measurements in the free water of milk. The volume of the
      sample, the technique used to extract the water and the level of dehydration
      modulate the results but in different ways: dispersion of results and under- or
      over-estimation of the tritium activity. The influence of sample storage and
      preparation has also been investigated. Methodological improvements of tritium
      measurements in the free water of milk are proposed. An original fractionation
      effect during distillation of milk is also described. 

PMID- 24113400
TI  - Characterization of single alpha-tracks by photoresist detection and AFM analysis
      focus on biomedical science and technology.
AB  - The interactions between energetic ions and biological and/or organic target
      materials have recently attracted theoretical and experimental attention, due to
      their implications for detector and device technologies, and for therapeutic
      applications. Most of the attention has focused on detection of the primary
      ionization tracks, and their effects, while recoil target atom tracks remain
      largely unexplored. Detection of tracks by a negative tone photoresist (SU-8),
      followed by standard development, in combination with analysis by atomic force
      microscopy, shows that both primary and recoil tracks are revealed as conical
      spikes, and can be characterized at high spatial resolution. The methodology has
      the potential to provide detailed information about single impact events, which
      may lead to more effective and informative detector technologies and advanced
      therapeutic procedures. In comparison with current characterization methods the
      advantageous features include: greater spatial resolution by an order of
      magnitude (20 nm); detection of single primary and associated recoil tracks;
      increased range of fluence (to 2.5 * 10(9) cm(-2)); sensitivity to impacts at
      grazing angle incidence; and better definition of the lateral interaction volume
      in target materials. 

PMID- 24113401
TI  - Near elimination of genital warts in Australia predicted with extension of human
      papillomavirus vaccination to males.
AB  - BACKGROUND: The National Human Papillomavirus (HPV) Vaccination Program for
      females delivering the quadrivalent vaccine Gardasil has been included in the
      National Immunisation Program in Australia since 2007. Sentinel surveillance data
      show that genital wart incidence has been steadily declining since then. The
      objective of this study was to estimate the additional impact on genital warts as
      a result of male vaccination, which was approved by the Australian government in
      2012 and commenced in 2013. METHODS: We use a mathematical model of HPV
      transmission in the Australian heterosexual population to predict the impact of
      male vaccination on the incidence of genital warts. RESULTS: Our model produced
      results that are consistent with the actual observed decline in genital warts and
      predicted a much lower incidence, approaching elimination, in coming decades with
      the introduction of male vaccination. CONCLUSIONS: Results from our model
      indicate that the planned extension of the National HPV Vaccination Program to
      males will lead to the near elimination of genital warts in both the female and
      male heterosexual populations in Australia.

PMID- 24113396
TI  - A risk prediction model for severe intraventricular hemorrhage in very low birth
      weight infants and the effect of prophylactic indomethacin.
AB  - OBJECTIVE: Develop a risk prediction model for severe intraventricular hemorrhage
      (IVH) in very low birth weight infants (VLBWI). STUDY DESIGN: Prospectively
      collected data of infants with birth weight 500 to 1249 g born between 2001 and
      2010 in centers from the Neocosur Network were used. Forward stepwise logistic
      regression model was employed. The model was tested in the 2011 cohort and then
      applied to the population of VLBWI that received prophylactic indomethacin to
      analyze its effect in the risk of severe IVH. RESULT: Data from 6538 VLBWI were
      analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in
      the 2011 cohort. The prophylactic indomethacin group had lower incidence of
      severe IVH, especially in the highest-risk groups. CONCLUSION: A model for early
      severe IVH prediction was developed and tested in our population. Prophylactic
      indomethacin was associated with a lower risk-adjusted incidence of severe IVH.

PMID- 24113399
TI  - Control of gene expression in Helicobacter pylori using the Tet repressor.
AB  - The lack of a versatile system to control gene expression in Helicobacter pylori
      has hampered efforts to study H. pylori physiology and pathogenesis. To overcome
      these limitations, we evaluated the utility of an inducible system based on the
      well-characterized Tet repressor (TetR) and Tet operator (tetO). As validation of
      this system, we introduced three copies of tetO into the promoter region upstream
      of the cagUT operon (encoding two virulence factors required for function of the
      H. pylori Cag type IV secretion system) and expressed tetR by introducing a codon
      optimized gene into the chromosomal ureA locus. Introduction of the tetO copies
      upstream of cagUT did not disrupt promoter activity, as determined by
      immunoblotting for CagT. The subsequent introduction of tetR, however, did
      repress CagT synthesis. Production of CagT was restored when strains were
      cultured in the presence of the inducer, anhydrotetracycline. To demonstrate one
      potential application of this new tool, we analyzed the function of the Cag type
      IV secretion system. When the modified H. pylori strains were co-cultured with
      AGS cells, activity of the Cag type IV secretion system was dependent on the
      presence of anhydrotetracycline as evidenced by inducer-dependent induction of IL
      8 secretion, CagA translocation, and appearance of type IV secretion system pili
      at the bacteria-host interface. These studies demonstrate the effectiveness of
      the tetR-tetO system to control gene expression in H. pylori and provide an
      improved system for studying H. pylori physiology and pathogenesis. 

PMID- 24113402
TI  - Sexual history taking and sexually transmitted infection screening in patients
      initiating erectile dysfunction medication therapy.
AB  - BACKGROUND: Erectile dysfunction medications are being prescribed frequently;
      however, little is known about the amount of sexual health screening occurring in
      this setting. METHODS: A retrospective cohort study evaluating sexual health and
      sexually transmitted infection screening occurring in veterans receiving initial
      erectile dysfunction medication prescription was conducted. RESULTS: A total of
      252 patients received initial erectile dysfunction medication prescriptions
      between October 1, 2009, and December 31, 2009; had at least 1 health care
      provider visit 12 months before the date of initial prescription; and had no
      documentation of previous erectile dysfunction medication use. Approximately 3%
      of these patients had any aspect of a sexual history recorded in the 24 months
      surrounding initial erectile dysfunction medication prescription. Sexually
      transmitted infection screening was 9.9% for syphilis, 4.8% for HIV, and 4.3% for
      gonorrhea/chlamydia before prescription, with only a slight increase in HIV
      screening after prescription. CONCLUSIONS: Minimal sexual health assessment is
      being performed during the time surrounding initial prescription of erectile
      dysfunction medication. Further work needs to evaluate patient and provider
      barriers to basic elements of sexual health care, such as taking sexual histories
      or screening for sexually transmitted infections.

PMID- 24113403
TI  - The footprint of old syphilis: using a reverse screening algorithm for syphilis
      testing in a U.S. Geographic Information Systems-Based Community Outreach
      Program.
AB  - The impact of syphilis reverse sequence screening has not been evaluated in
      community outreach. Using reverse sequence screening in neighborhoods identified
      with geographic information systems, we found that among 239 participants, 45
      (19%) were seropositive. Of these, 3 (7%) had untreated syphilis, 33 (73%) had
      previously treated syphilis infection, and 9 (20%) had negative nontreponemal
      test results. 

PMID- 24113404
TI  - Positive Chlamydia trachomatis serology result in women seeking care for
      infertility is a negative prognosticator for intrauterine pregnancy.
AB  - BACKGROUND: There are no prior studies that assess the non-in vitro fertilization
      (IVF) pregnancy rates in chlamydia serology-positive versus serology-negative
      women. Therefore, we wanted to determine whether a positive Chlamydia trachomatis
      immunoglobulin G serology result predicts reduced clinical pregnancy rates
      without IVF. METHODS: A prospective observational study was performed at a
      university-affiliated reproductive center. A total of 1279 new infertility
      patients seen at the Continuum Reproductive Center between January 2007 and June
      2009 underwent C. trachomatis immunoglobulin G screening. Charts were later
      reviewed for hysterosalpingography, laparoscopy, treatment cycles, and ultrasound
      evidence of an intrauterine pregnancy. The main outcome measure was non-IVF
      cumulative pregnancy rates. RESULTS: Seventy (5.5%) of 1279 of the participants
      were found to have a positive chlamydia serology result. Serology-positive
      participants had significantly more tubal block on hysterosalpingography (37.5%
      vs. 10.1%, P = 0.001) and laparoscopically confirmed tubal damage (85.7% vs.
      48.9%, P = 0.002). The percent of all participants who achieved an ultrasound
      documented clinical pregnancy, at our center, without IVF was significantly lower
      among Chlamydia-positive participants (10.0% versus 21.7%) in seronegative
      participants (P < 0.02). The hazard rate of non-IVF clinical pregnancy among
      chlamydia antibody testing-positive patients was 57% less than the rate of
      pregnancy among chlamydia antibody testing-negative patients (hazard ratio, 0.43;
      95% confidence interval, 0.20-0.92). Both the per-cycle and the cumulative IVF
      pregnancy rates were equivalent in seropositive and in seronegative participants.
      CONCLUSIONS: This is the first large study to report that a positive serology
      screening result is both predictive of tubal damage and a reduced cumulative
      pregnancy rate when excluding treatment with IVF.

PMID- 24113405
TI  - Integration of preventing mother-to-child transmission of HIV and syphilis
      testing and treatment in antenatal care services in the Northern Cape and Gauteng
      provinces, South Africa.
AB  - BACKGROUND: South Africa recommends universal syphilis and HIV testing in
      pregnancy, with prompt antiretroviral therapy or penicillin treatment for women
      testing positive. METHODS: We used a multistage, purposeful sampling strategy to
      retrospectively identify clinical records from a sample (7.3%) of 32,518 women
      delivering from January 2005 to June 2006 at 6 public clinics in the Northern
      Cape and Gauteng. Descriptive analyses and logistic regression were used to
      assess coverage and factors related to testing and treatment of HIV and syphilis.
      RESULTS: Of 2379 women sampled, 93% accessed antenatal care (ANC) services during
      pregnancy and 71% before the third pregnancy trimester. Testing during pregnancy
      or delivery was 74% for HIV and 84% for syphilis; testing at the first ANC visit
      was 41% and 71%; and infection prevalence at delivery was 14% and 5%,
      respectively. Of 243 women with reactive HIV tests, 104 (43%) had treatment
      documented (single-dose nevirapine) before delivery. Of 98 women with reactive
      syphilis tests, 73% had documented receipt of 1 penicillin injection and 36% had
      all 3 recommended injections. Multivariable analysis found women tested for
      syphilis were almost 4 times more likely to have had no HIV test compared with
      those without syphilis testing (adjusted odds ratios, 3.9; 95% confidence
      interval, 1.7-5.5). CONCLUSIONS: Integration and provision of a package of HIV
      and syphilis testing at the first ANC visit and decentralizing treatments of both
      infections to primary care settings could increase the coverage of testing and
      treatment services, thus enhancing the effectiveness of current programs
      eliminating mother-to-child transmission of HIV and syphilis.

PMID- 24113406
TI  - Syphilitic posterior placoid chorioretinitis.
AB  - We present a case of syphilitic posterior placoid chorioretinitis, an uncommon
      but distinct ocular manifestation of syphilis. Because of the ocular findings, a
      lumbar puncture was performed to evaluate for neurosyphilis, which was positive.
      The ocular symptoms resolved with intravenous penicillin. 

PMID- 24113407
TI  - Image-based noninvasive evaluation of colorectal mucosal injury in sheep after
      topical application of microbicides.
AB  - BACKGROUND: Successful development of topical rectal microbicides requires
      preclinical evaluation in suitable large animal models. Our previous studies have
      demonstrated the benefits of high-resolution optical coherence tomography (OCT)
      to visualize subclinical microbicide toxicity in the sheep vagina. In the current
      study, we evaluated the potential application of colonoscopy and OCT to visualize
      and quantify the effects of topical products on sheep colorectal tissue, as
      assessed by advanced imaging techniques. METHODS: Yearling virginal female sheep
      were treated rectally with a single 8-mL dose of 0.2% benzalkonium chloride (BZK)
      solution or phosphate-buffered saline control. Imaging was performed before and
      30 minutes after treatment. Colonoscopy findings were evaluated based on mucosal
      disruption. Optical coherence tomography images were graded based on the
      integrity of the mucosal layer. Biopsies collected after treatment were evaluated
      by histology for validation of OCT scoring. RESULTS: Mucosal disruption was
      observed by colonoscopy in BZK-treated animals, whereas none was present in
      controls. In contrast to colonoscopy, high-resolution in-depth OCT imaging
      provided visualization of the morphology of the mucosal layer and underlying
      muscularis, thus enabling detection of microscopic abnormalities. Noninvasive
      quantification of drug-induced injury after validation of the scoring system
      (categories 1, 2, 3) showed increased scores after treatment with BZK (P <
      0.001), indicating mucosal injury. CONCLUSIONS: High-resolution OCT can be used
      as highly sensitive tool to evaluate rectal microbicide effects. Because the
      sheep rectum has both gross and microscopic similarities to the human, this model
      is a useful addition to current methods of rectal product toxicity.

PMID- 24113408
TI  - Trends in seroprevalence of herpes simplex virus type 2 among non-Hispanic blacks
      and non-Hispanic whites aged 14 to 49 years--United States, 1988 to 2010.
AB  - OBJECTIVES: Genital herpes simplex virus type 2 (HSV-2) is one of the most
      prevalent sexually transmitted infections in the United States. We sought to
      assess differences in HSV-2 seroprevalence among non-Hispanic blacks and non
      Hispanic whites and describe trends over time from 1988 to 2010. METHODS: Data
      from National Health and Nutrition Examination Surveys (NHANES) were used to
      determine national HSV-2 seroprevalence estimates from National Health and
      Nutrition Examination Surveys 1988 to 1994, 1999 to 2002, 2003 to 2006, and 2007
      to 2010. Persons aged 14 to 49 years were included in the analyses.
      Race/Ethnicity was defined by self-report as non-Hispanic white or non-Hispanic
      black. Purified glycoprotein specific for HSV-2 was used to detect type-specific
      antibodies using an immunodot assay. The same assay was used in all surveys.
      History of diagnosed genital herpes was self-reported. RESULTS: Overall, HSV-2
      seroprevalence decreased in the United States between 1988 to 1994 and 2007 to
      2010, from 21.2% to 15.5%. Among non-Hispanic white females, HSV-2 seroprevalence
      decreased from 19.5% (1988-1994) to 15.3% (2007-2010; P < 0.001); HSV-2
      seroprevalence remained stable among non-Hispanic black females, 52.5% (1988
      1994) to 49.9% (2007-2010; P = 0.1). The female black/white prevalence ratio was
      2.7 (95% confidence interval [CI], 2.4-3.0) in 1988 to 1994 increasing to 3.3
      (95% CI, 2.9-3.7) in 2007 to 2010 (P = 0.01). Among males, the black/white
      prevalence ratio was 2.4 (95% CI, 1.9-2.9) in 1988 to 1994 increasing to 4.4 (95%
      CI, 3.3-5.8) in 2007 to 2010 (P = 0.001). The overall percentage of HSV-2
      seropositive survey participants who reported never being told by a doctor or
      health care professional that they had genital herpes did not change
      significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and
      87.4%, respectively). CONCLUSIONS: Although HSV-2 seroprevalence decreased
      overall, the decrease was most marked among non-Hispanic whites, and racial
      disparities significantly increased over time. These persistent disparities
      demonstrate the need for innovative prevention strategies among this at-risk
      population.

PMID- 24113409
TI  - Trichomonas vaginalis in selected U.S. sexually transmitted disease clinics:
      testing, screening, and prevalence.
AB  - BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually
      transmitted infection in the United States, affecting 3.1% of women of
      reproductive age. Infection is associated with HIV acquisition and pelvic
      inflammatory disease. In the United States, Centers for Disease Control and
      Prevention guidelines recommend testing all women with vaginal discharge for T.
      vaginalis, but except for HIV-infected women, there are no national guidelines
      for screening asymptomatic persons. The objective of this analysis is to assess
      testing and screening practices for T. vaginalis among symptomatic and
      asymptomatic women in the sexually transmitted disease (STD) clinic setting.
      METHODS: We analyzed data on demographics, clinical presentation, and laboratory
      testing for all women visiting a clinician in 2010 to 2011 at any of 15 STD
      clinics participating in the STD Surveillance Network. Prevalence of laboratory
      confirmed T. vaginalis infection was calculated among symptomatic women tested
      and among asymptomatic women screened. RESULTS: A total of 59,176 women visited
      STD clinicians: 39,979 were considered symptomatic and 19,197 were considered
      asymptomatic for T. vaginalis infection, whereas 211 were HIV-infected.
      Diagnostic practices varied by jurisdiction: 4.0% to 96.1% of women were tested
      or screened for T. vaginalis using any laboratory test. Among 17,952 symptomatic
      women tested, prevalence was 26.2%. Among 3909 asymptomatic women screened,
      prevalence was 6.5%. Among 92 HIV-infected women tested/screened, prevalence was
      29.3%. CONCLUSIONS: Trichomoniasis is common among STD clinic patients. In this
      analysis, most STD clinics tested symptomatic women seeking care, in accordance
      with national guidelines. All HIV-infected women should be screened annually.
      Additional evidence and national guidance are needed regarding potential benefits
      of T. vaginalis screening in other asymptomatic women.

PMID- 24113410
TI  - Effect of multiple freeze and thaw cycles on the sensitivity of IgG and IgM
      immunoglobulins in the sera of patients with syphilis.
AB  - We describe the effects of multiple freeze and thaw cycles on the sensitivity of
      the immunoglobulins IgG and IgM measured by enzyme-linked immunoassays in the
      sera of patients with syphilis. Stored frozen sera can withstand repeated
      freezing and thawing cycles with a minimal detrimental effect on the sensitivity
      of the sera. 

PMID- 24113411
TI  - Prevalence and molecular epidemiological typing of penicillinase-producing
      Neisseria gonorrhoeae and their bla(TEM-135) gene variants in Nanjing, China.
AB  - BACKGROUND: This study aimed to investigate the prevalence of penicillinase
      producing Neisseria gonorrhoeae (PPNG) and their blaTEM-135 gene variant in 2007
      and 2012 in Nanjing, China. In addition, molecular epidemiological typing of all
      isolates was performed to elucidate the genetic relationships of the PPNG
      strains. METHODS: A total of 199 and 77 N. gonorrhoeae isolates were collected at
      the National Center for STD Control in 2007 and 2012, respectively. Nitrocefin
      tests were performed to identify PPNG. Mismatch amplification mutation assay was
      used to identify blaTEM-135. All isolates were genotyped using N. gonorrhoeae
      multiantigen sequence typing (NG-MAST), and additionally, porB-based phylogenetic
      analysis was performed for the PPNG isolates. RESULTS: The total prevalence of
      PPNG isolates was 41% (114/276) and 58% (66/114) of these PPNG isolates possessed
      bla(TEM-135). In 2007, 45% (90/199) produced beta-lactamase, and of those PPNG,
      58% (52/90) possessed bla(TEM-135). In 2012, 31% (24/77) were PPNG, and 58%
      (14/24) of those isolates contained bla(TEM-135). There were 162 NG-MAST STs
      among the 276 isolates, and 89 of those were novel STs. A strong association
      between specific NG-MAST STs and bla(TEM-135) was found, and the porB-based
      phylogenetic analysis showed a distant evolutionary relationship between isolates
      in 2007 and isolates in 2012. CONCLUSIONS: A high prevalence of PPNG and blaTEM
      135 was found in Nanjing, China. bla(TEM-135) might be a precursor in the
      evolution into an extended-spectrum beta-lactamase that can degrade ceftriaxone,
      which stresses the need to continuously monitor PPNG, blaTEM-135, and additional
      evolving blaTEM gene variants.

PMID- 24113412
TI  - Retrospective review of pharyngeal gonorrhea treatment failures in Alberta,
      Canada.
AB  - Our review of Neisseria gonorrhoeae pharyngeal treatment failures from sexually
      transmitted infection clinics in Alberta suggests that treatment failures with
      oral cefixime monotherapy were not related to elevated cefixime minimum
      inhibitory concentrations. Dual therapy with oral cefixime and azithromycin may
      be a suitable alternate for the treatment of pharyngeal gonorrhea. 

PMID- 24113413
TI  - Filiform papules on the labia minora.

PMID- 24113414
TI  - Expedited partner therapy in federally qualified health centers--New York City,
      2012.
AB  - BACKGROUND: Management of patients' sex partners is a critical element of
      sexually transmitted disease (STD) control. Expedited partner therapy (EPT), a
      practice in which patients deliver medication or a prescription directly to their
      partners, is one option for partner management. As of 2009, New York State law
      specifically allows EPT for chlamydial infection. Federally qualified health
      centers (FQHCs) in New York City (NYC) care for patients at risk for STDs. We
      describe the policies and practices surrounding EPT and other STD management in
      NYC FQHCs. METHODS: In 2012, we surveyed medical directors at all NYC FQHC parent
      entities and clinicians at a sample of their corresponding clinical sites about
      written policies and actual practices regarding EPT for chlamydial infection and
      other STD management. RESULTS: Twenty-two entities (22/29; 76%) and 51 sites
      (51/72; 70%) responded to the survey. More than half of entities have a written
      policy permitting EPT, and 80% of sites provide EPT. Most entity policies allow
      EPT for, and most sites provide EPT to, adolescents and adults with both opposite
      sex and/or same-sex partners. Most sites use electronic health records and
      provide EPT by prescriptions, and one third of sites do not provide educational
      materials with EPT. CONCLUSIONS: Our results indicate widespread EPT provision by
      NYC FQHCs; however, areas for improvement exist, specifically in following
      guidelines that recommend providing educational materials with EPT and do not
      recommend EPT for men with male partners. The use of prescriptions for EPT and
      electronic health records were identified as potential barriers to EPT provision.

PMID- 24113415
TI  - Toward enhancing sexually transmitted infection clinic efficiency in an era of
      molecular diagnostics: the role of physical examination and risk stratification
      in men.
AB  - BACKGROUND: In an era of constrained resources, new molecular techniques may make
      it possible to detect common sexually transmitted infections (STIs) without
      physical examination in selected groups of men. Our objectives were to define the
      contribution of the physical examination in detecting clinically meaningful
      diagnoses that may not be identified by current laboratory methods and to
      identify characteristics that can stratify men into the appropriate risk
      category. METHODS: A retrospective study from a database of all male visits to 2
      urban STI clinics in Baltimore between 1990 and 2001 was conducted. Men were
      stratified on the basis of reason for visit. Proportions for diagnoses that would
      have been missed without physical examination were compared using the chi2 test.
      Logistic regression was used to assess which factors were most predictive of
      missed diagnoses. RESULTS: A total of 58,073 of 140,052 records were included:
      29,172 were asymptomatic, 23,972 were symptomatic, and 4929 were asymptomatic
      contacts of an infected partner. In addition, 2.7% of ASYM, 10.4% of symptomatic,
      and 4.5% of contact patients would have had missed diagnoses if no physical
      examination had been performed. For symptomatic patients, if those reporting
      rash, lesion, or genital itch were examined, the percent with missed diagnoses
      would drop to 3.7%. CONCLUSIONS: Asymptomatic men may be candidates for
      accelerated STI testing, which includes the submission of genital and
      extragenital swabs as well as blood samples for HIV and syphilis testing without
      a physical examination. A significant proportion of symptomatic men would miss
      the opportunity for same-day treatment of gonococcal or nongonococcal urethritis.

PMID- 24113416
TI  - Adolescents' attitudes toward expedited partner therapy for sexually transmitted
      infections.
AB  - Adolescents (N = 392) attending 2 urban adolescent health clinics in 2010 were
      surveyed regarding likelihood completing expedited partner therapy (EPT), by
      bringing a partner exposed to chlamydia a prescription. Eighty-five percent
      (330/387; 95% confidence interval, 81%-89%), reported acceptance of EPT. Adjusted
      analyses showed higher education, notification self-efficacy, and romantic
      partner were associated with EPT acceptance. 

PMID- 24113417
TI  - Crystal field and magnetism of Pr3+ and Nd3+ ions in orthorhombic perovskites.
AB  - Fifteen parameters characterizing the crystal field of rare-earth ions in the
      RMO3 perovskites (R=Pr, Nd, M=Ga, Co) are calculated using a first-principles
      electronic structure and the Wannier projection. The method contains a single
      adjustable parameter that characterizes the hybridization of R(4f) states with
      the states of oxygen ligands. Subsequently the energy levels and magnetic moments
      of the trivalent R ion are determined by diagonalization of an effective
      Hamiltonian which, besides the crystal field, contains the 4f electron-electron
      repulsion, spin-orbit coupling and interaction with magnetic field. In the Ga
      compounds the energy levels of the ground multiplet agree within a few meV with
      those determined experimentally by other authors. For all four compounds in
      question the temperature dependence of magnetic susceptibility is measured on
      polycrystalline samples and compared with the results of calculation. For NdGaO3
      the theory is also compared with the magnetic measurements on a single crystal
      presented by Luis et al (1998 Phys. Rev. B 58 798). Good agreement between the
      experiment and theory is found.

PMID- 24113419
TI  - Theoretical study of the photochemical generation of triplet acetophenone.
AB  - Acetophenone has a rich photochemistry, which strongly depends on the absorbing
      state. For example, the excitation to the lowest singlet excited state (S1) leads
      to a triplet population with a phosphorescence quantum yield of one, while the
      excitation to S2 leads to photocleavage reactions. Here, we rationalize the
      photochemistry of acetophenone after being absorbed into the S1, S2 and S3 states
      by performing a systematic study of all the singlet and triplet minimum energy
      structures and state crossings between the relevant electronic states. We
      calculate these structures at the complete-active space self-consistent field
      (CASSCF) level of theory and at the correlated extended second-order quasi
      degenerate multi-reference perturbation theory (XMCQDPT2), emphasizing the
      importance of correlation effects in the determination of structures. 

PMID- 24113418
TI  - Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect
      of hyperbaric oxygen in mice.
AB  - Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2)
      can elicit an antinociceptive response in models of acute pain. We have
      demonstrated that this antinociceptive effect is centrally-mediated and is
      dependent on opioid receptors. The purpose of the present study was to examine
      the role of endogenous opioid peptides and opioid receptors specifically in the
      spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss
      mice were exposed to HBO2 (100% oxygen at 3.5atm absolute) for 11min and their
      antinociceptive responsiveness was determined using the glacial acetic acid
      induced abdominal constriction test. HBO2-induced antinociception was sensitive
      to antagonism by intrathecal (i.t.) pretreatment with the kappa- and MU-selective
      opioid antagonists norbinaltorphimine and beta-funaltrexamine, respectively, but
      not the delta-selective antagonist naltrindole. The antinociceptive effect of
      HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit
      antiserum against rat dynorphin1-13 but not antisera against beta-endorphin or
      methionine-enkephalin. Based on these experimental findings, the acute
      antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin
      and activation of kappa- and MU-opioid receptors in the spinal cord. 

PMID- 24113420
TI  - Accelerated event-by-event Monte Carlo microdosimetric calculations of electrons
      and protons tracks on a multi-core CPU and a CUDA-enabled GPU.
AB  - For microdosimetric calculations event-by-event Monte Carlo (MC) methods are
      considered the most accurate. The main shortcoming of those methods is the
      extensive requirement for computational time. In this work we present an event-by
      event MC code of low projectile energy electron and proton tracks for accelerated
      microdosimetric MC simulations on a graphic processing unit (GPU). Additionally,
      a hybrid implementation scheme was realized by employing OpenMP and CUDA in such
      a way that both GPU and multi-core CPU were utilized simultaneously. The two
      implementation schemes have been tested and compared with the sequential single
      threaded MC code on the CPU. Performance comparison was established on the speed
      up for a set of benchmarking cases of electron and proton tracks. A maximum
      speedup of 67.2 was achieved for the GPU-based MC code, while a further
      improvement of the speedup up to 20% was achieved for the hybrid approach. The
      results indicate the capability of our CPU-GPU implementation for accelerated MC
      microdosimetric calculations of both electron and proton tracks without loss of
      accuracy. 

PMID- 24113421
TI  - A hybrid semi-automatic method for liver segmentation based on level-set methods
      using multiple seed points.
AB  - The present study developed a hybrid semi-automatic method to extract the liver
      from abdominal computerized tomography (CT) images. The proposed hybrid method
      consists of a customized fast-marching level-set method for detection of an
      optimal initial liver region from multiple seed points selected by the user and a
      threshold-based level-set method for extraction of the actual liver region based
      on the initial liver region. The performance of the hybrid method was compared
      with those of the 2D region growing method implemented in OsiriX using abdominal
      CT datasets of 15 patients. The hybrid method showed a significantly higher
      accuracy in liver extraction (similarity index, SI=97.6 +/- 0.5%; false positive
      error, FPE = 2.2 +/- 0.7%; false negative error, FNE=2.5 +/- 0.8%; average
      symmetric surface distance, ASD=1.4 +/- 0.5mm) than the 2D (SI=94.0 +/- 1.9%; FPE
      = 5.3 +/- 1.1%; FNE=6.5 +/- 3.7%; ASD=6.7 +/- 3.8mm) region growing method. The
      total liver extraction time per CT dataset of the hybrid method (77 +/- 10 s) is
      significantly less than the 2D region growing method (575 +/- 136 s). The
      interaction time per CT dataset between the user and a computer of the hybrid
      method (28 +/- 4 s) is significantly shorter than the 2D region growing method
      (484 +/- 126 s). The proposed hybrid method was found preferred for liver
      segmentation in preoperative virtual liver surgery planning.

PMID- 24113422
TI  - A model-based method for computation of correlation dimension, Lyapunov exponents
      and synchronization from depth-EEG signals.
AB  - In order to predict epileptic seizures many precursory features, extracted from
      the EEG signals, have been introduced. Before checking out the performance of
      features in detection of pre-seizure state, it is required to see whether these
      features are accurately extracted. Evaluation of feature estimation methods has
      been less considered, mainly due to the lack of a ground truth for the real EEG
      signals' features. In this paper, some simulated long-term depth-EEG signals,
      with known state spaces, are generated via a realistic neural mass model with
      physiological parameters. Thanks to the known ground truth of these synthetic
      signals, they are suitable for evaluating different algorithms used to extract
      the features. It is shown that conventional methods of estimating correlation
      dimension, the largest Lyapunov exponent, and phase coherence have non-negligible
      errors. Then, a parameter identification-based method is introduced for
      estimating the features, which leads to better estimation results for synthetic
      signals. It is shown that the neural mass model is able to reproduce real depth
      EEG signals accurately; thus, assuming this model underlying real depth-EEG
      signals, can improve the accuracy of features' estimation. 

PMID- 24113423
TI  - Validity and reliability of isometric, isokinetic and isoinertial modalities for
      the assessment of quadriceps muscle strength in patients with total knee
      arthroplasty.
AB  - Reliability of isometric, isokinetic and isoinertial modalities for quadriceps
      strength evaluation, and the relation between quadriceps strength and physical
      function was investigated in 29 total knee arthroplasty (TKA) patients, with an
      average age of 63 years. Isometric maximal voluntary contraction torque,
      isokinetic peak torque, and isoinertial one-repetition maximum load of the
      involved and uninvolved quadriceps were evaluated as well as objective (walking
      parameters) and subjective physical function (WOMAC). Reliability was good and
      comparable for the isometric, isokinetic, and isoinertial strength outcomes on
      both sides (intraclass correlation coefficient range: 0.947-0.966; standard error
      of measurement range: 5.1-9.3%). Involved quadriceps strength was significantly
      correlated to walking speed (r range: 0.641-0.710), step length (r range: 0.685
      0.820) and WOMAC function (r range: 0.575-0.663), independent from the modality
      (P < 0.05). Uninvolved quadriceps strength was also significantly correlated to
      walking speed (r range: 0.413-0.539), step length (r range: 0.514-0.608) and
      WOMAC function (r range: 0.374-0.554) (P < 0.05), except for WOMAC
      function/isokinetic peak torque (P > 0.05). In conclusion, isometric, isokinetic,
      and isoinertial modalities ensure valid and reliable assessment of quadriceps
      muscle strength in TKA patients.

PMID- 24113424
TI  - Effects of different movement directions on electromyography recorded from the
      shoulder muscles while passing the target positions.
AB  - PURPOSE: We compared electromyography (EMG) recorded from the shoulder joint
      muscles in the same position for different movement directions. METHODS: Fifteen
      healthy subjects participated. They performed shoulder elevation from 0 degrees 
      to 120 degrees , shoulder depression from 120 degrees  to 0 degrees , shoulder
      horizontal adduction from -15 degrees  to 105 degrees , and shoulder horizontal
      abduction from 105 degrees  to -15 degrees . The target positions were 90 degrees
      shoulder elevation in the 0 degrees , 30 degrees , 60 degrees , and 90 degrees 
      planes (0 degrees , 30 degrees , 60 degrees , and 90 degrees  positions). EMG
      signals were recorded from the supraspinatus (SSP) muscle by fine-wire
      electrodes. EMG signals from the infraspinatus (ISP), anterior deltoid, middle
      deltoid, and posterior deltoid muscles were recorded using active surface
      electrodes. RESULTS: During elevation and horizontal abduction, the SSP showed
      significantly higher activity than that shown during depression and during
      horizontal adduction in the 0 degrees , 30 degrees , and 60 degrees  positions.
      During elevation, the ISP showed significantly higher activity than during
      depression and during horizontal adduction in the 90 degrees  position. During
      horizontal abduction, the ISP showed significantly higher activity than during
      depression in the 90 degrees  position. CONCLUSIONS: When the movement tasks were
      performed in different movement directions at the same speed, each muscle showed
      characteristic activity.

PMID- 24113425
TI  - Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory
      effects of mesenchymal stromal cells in models of acute organ injury.
AB  - The purpose of this review is to systematize data from many studies and
      observations of proliferative, anti-apoptotic and anti-inflammatory effects of
      mesenchymal stromal cell (MSC) paracrine factors and their biologic effects in
      models of acute organ injury. 

PMID- 24113426
TI  - Mesenchymal stromal cells from unconventional model organisms.
AB  - Mesenchymal stromal cells (MSCs) are multipotent, plastic, adherent cells able to
      differentiate into osteoblasts, chondroblasts and adipocytes. MSCs can be
      isolated from many different body compartments of adult and fetal individuals.
      The most commonly studied MSCs are isolated from humans, mice and rats. However,
      studies are also being conducted with the use of MSCs that originate from
      different model organisms, such as cats, dogs, guinea pigs, ducks, chickens,
      buffalo, cattle, sheep, goats, horses, rabbits and pigs. MSCs derived from
      unconventional model organisms all present classic fibroblast-like morphology,
      the expression of MSC-associated cell surface markers such as CD44, CD73, CD90
      and CD105 and the absence of CD34 and CD45. Moreover, these MSCs have the ability
      to differentiate into osteoblasts, chondroblasts and adipocytes. The MSCs
      isolated from unconventional model organisms are being studied for their
      potential to heal different tissue defects and injuries and for the development
      of scaffold compositions that improve the proliferation and differentiation of
      MSCs for tissue engineering. 

PMID- 24113427
TI  - Activation of extracellular signal-regulated kinase 1/2 and Sp1 may contribute to
      the expression of tissue inhibitor of metalloproteinases-1 induced by
      transforming growth factor-beta1 in human pulmonary arterial smooth muscle cells.
AB  - BACKGROUND AIMS: Tissue inhibitor of metalloproteinases-1 (TIMP-1) plays an
      important role in the development of pulmonary arterial hypertension. However,
      the molecular regulatory mechanisms of TIMP-1 in the pulmonary arteries are not
      fully understood, especially in human pulmonary arterial smooth muscle cells
      (HPASMCs). We investigated the signaling pathway involved in the regulation of
      TIMP-1 in HPASMCs induced by transforming growth factor (TGF)-beta1. METHODS:
      Cultured HPASMCs were incubated with different concentrations of TGF-beta1 (0-40
      ng/mL) for 24 h or with 10 ng/mL TGF-beta1 for different times (1-48 h). RESULTS:
      Western blot, real-time polymerase chain reaction and enzyme-linked immunosorbent
      assay analyses showed that TGF-beta1 enhanced the expression and secretion of
      TIMP-1 in a time-dependent and dose-dependent fashion. TGF-beta1 could
      phosphorylate two of the three mitogen-activated protein kinases-extracellular
      signal-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun NH2-terminal kinase.
      Of these kinases, only the inhibition of ERK1/2 by U0126, which was a specific
      inhibitor of mitogen-activated protein kinase/ERK1/2, effectively blocked the TGF
      beta1-induced expression of TIMP-1. Mithramycin, an inhibitor of Sp1
      transcription factor, also significantly inhibited the expression of TIMP-1.
      Additionally, electrophoretic mobility shift assay showed that TGF-beta1 could up
      regulate the DNA-binding activity of Sp1 and that U0126 and mithramycin could
      effectively inhibit these events. CONCLUSIONS: TGF-beta1 could stimulate the
      expression and secretion of TIMP-1 in HPASMCs in a time-dependent and dose
      dependent fashion, and ERK1/2 and Sp1 signaling pathways might be involved in
      these activities.

PMID- 24113428
TI  - Regulation of advanced therapy medicinal products in Europe and the role of
      academia.
AB  - BACKGROUND AIMS: Advanced therapy medicinal products (ATMP) are gene therapy,
      somatic cell therapy or tissue-engineered products regulated under (EC) No.
      1394/2007 to ensure their free movement within the European Union while
      guaranteeing the highest level of health protection for patients. Academic good
      manufacturing practice (GMP) centers are major contributors in the development of
      ATMPs and this study assessed the impact of regulations on them. METHODS:
      European academic and non-industrial facilities (n = 747) were contacted, and a
      representative sample of 50 replied to a detailed questionnaire. Experienced
      centres were further selected in every Member State (MS) for semi-structured
      interviews. Indicators of ATMP production and development success were
      statistically assessed, and opinions about directive implementation were
      documented. RESULTS: Facilities experienced in manufacturing cell therapy
      transplant products are the most successful in developing ATMPs. New centres
      lacking this background struggle to enter the field, and there remains a shortage
      of facilities in academia participating in translational research. This is
      compounded by heterogeneous implementation of the regulations across MS.
      CONCLUSIONS: GMP facilities successfully developing ATMPs are present in all MS.
      However, the implementation of regulations is heterogeneous between MS, with
      substantial differences in the definition of ATMPs and in the approved
      manufacturing environment. The cost of GMP compliance is underestimated by
      research funding bodies. This is detrimental to development of new ATMPs and
      commercialization of any that are successful in early clinical trials. Academic
      GMP practitioners should strengthen their political visibility and contribute to
      the development of functional and effective European Union legislation in this
      field.

PMID- 24113429
TI  - Human amniotic epithelial cells induce apoptosis of cancer cells: a new anti
      tumor therapeutic strategy.
AB  - BACKGROUND AIMS: Amniotic membrane (AM), the innermost layer of human placenta,
      is composed of a single layer of epithelial cells, a basement membrane and an
      avascular stroma. The AM has many functions and properties, among which
      angiogenic modulatory and immunoregulatory effects are applicable in cancer
      therapy. Because these functions belong to amniotic epithelial cells, in this
      study we compared the anti-cancer effect of amniotic epithelial cells and the
      whole AM. METHODS: The effect of the AM and the amniotic epithelial cells on
      cancer cell apoptosis was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium assay, terminal deoxynucleotidyl transferase dUTP nick end
      labeling assay and immunocytochemistry. The effect of the AM on angiogenesis in
      conditions both with and without epithelial cells was also evaluated using rat
      aortic ring assay. RESULTS: There was a decrease in cancer cell viability after
      adding either AM or amniotic epithelial cell supernatant to cancer cells. A
      significant increase in caspase-3 and caspase-8 expression in cancer cells
      treated with amniotic epithelial cell supernatant was observed. The recorded
      media also demonstrated the possible induction of apoptosis in cancer cells
      treated with the amniotic epithelial cell supernatant. In the aorta ring assay,
      the AM showed an anti-angiogenic effect in the presence of its epithelial cells;
      however, this effect was altered to initiate angiogenesis when amniotic
      epithelial cells were removed from the AM. CONCLUSIONS: These results suggest
      that amniotic epithelial cells, with their anti-angiogenic effect and induction
      of apoptosis, are candidates for cancer therapeutic agents in the near future.

PMID- 24113430
TI  - Incremental benefits of repeated mesenchymal stromal cell administration compared
      with solitary intervention after myocardial infarction.
AB  - BACKGROUND AIMS: Traditionally, stem cell therapy for myocardial infarction (MI)
      has been administered as a single treatment in the acute or subacute period after
      MI. These time intervals coincide with marked differences in the post-infarct
      myocardial environment, raising the prospect that repeat cell dosing could
      provide incremental benefit beyond a solitary intervention. This prospect was
      evaluated with the use of mesenchymal stromal cells (MSCs). METHODS: Three groups
      of rats were studied. Single-therapy and dual-therapy groups received allogeneic,
      prospectively isolated MSCs (1 * 10(6) cells) by trans-epicardial injection
      immediately after MI, with additional dosing 1 week later in the dual-therapy
      cohort. Control animals received cryopreservant solution only. Left ventricular
      (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic
      resonance immediately before MI and at 1, 2 and 4 weeks after MI. RESULTS:
      Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 +/-
      3.1% (dual group, n = 12) and 35.2 +/- 2.2% (single group, n = 15) at 1 week
      after MI compared with 22.1 +/- 1.9% in controls (n = 17, P < 0.01). In animals
      receiving a second dose of MSCs, EF increased to 40.7 +/- 3.1% by week 4, which
      was significantly higher than in the single-therapy group (EF 35.9 +/- 1.8%, P <
      0.05). Dual MSC treatment was also associated with greater myocardial mass and
      arteriolar density, with trends toward reduced myocardial fibrosis. These
      incremental benefits were especially observed in remote (non-infarct) segments of
      LV myocardium. CONCLUSIONS: Repeated stem cell intervention in both the acute and
      the sub-acute period after MI provides additional improvement in ventricular
      function beyond solitary cell dosing, largely owing to beneficial changes remote
      to the area of infarction.

PMID- 24113431
TI  - Bone suppressed images improve radiologists' detection performance for pulmonary
      nodules in chest radiographs.
AB  - OBJECTIVES: To assess the effect of bone suppression imaging on observer
      performance in detecting lung nodules in chest radiographs. MATERIALS AND
      METHODS: Posteroanterior (PA) and lateral digital chest radiographs of 111
      (average age 65) patients with a CT proven solitary nodule (median diameter 15
      mm), and 189 (average age 63) controls were read by 5 radiologists and 3
      residents. Conspicuity of nodules on the radiographs was classified in obvious (n
      = 32), moderate (n = 32), subtle (n = 29) and very subtle (n = 18). Observers
      read the PA and lateral chest radiographs without and with an additional PA bone
      suppressed image (BSI) (ClearRead Bone Suppression 2.4, Riverain Technologies,
      Ohio) within one reading session. Multi reader multi case (MRMC) receiver
      operating characteristics (ROC) were used for statistical analysis. RESULTS: ROC
      analysis showed improved detection with use of BSI compared to chest radiographs
      alone (AUC = 0.883 versus 0.855; p = 0.004). Performance also increased at high
      specificities exceeding 80% (pAUC = 0.136 versus 0.124; p = 0.0007). Operating at
      a specificity of 90%, sensitivity increased with BSI from 66% to 71% (p =
      0.0004). Increase of detection performance was highest for nodules with moderate
      and subtle conspicuity (p = 0.02; p = 0.03). CONCLUSION: Bone suppressed images
      improve radiologists' detection performance for pulmonary nodules, especially for
      those of moderate and subtle conspicuity.

PMID- 24113432
TI  - Body surface area adapted iopromide 300 mg/ml versus 370 mg/ml contrast medium
      injection protocol: influence on quantitative and clinical assessment in combined
      PET/CT.
AB  - PURPOSE: To investigate the quantitative and qualitative differences between
      combined positron emission tomography and computed X-ray tomography (PET/CT)
      enhanced with contrast medium with either an iodine concentration 300 mg/ml or
      370 mg/ml. MATERIALS AND METHODS: 120 consecutive patients scheduled for F-18
      Fluorodeoxyglucose (FDG) PET/CT were included. The first (second) 60 patients
      received contrast medium with 300 (370) mg iodine/ml. Intravenous injection
      protocols were adapted for an identical iodine delivery rate (1.3mg/s) and body
      surface area (BSA) adapted iodine dose (22.26 gI/m(2)). Maximum and mean
      standardized uptake values (SUV(max); SUV(mean)) and contrast enhancement (HU)
      were determined in the ascending aorta, the abdominal aorta, the inferior vena
      cava, the portal vein, the liver and the right kidney in the venous contrast
      medium phase. PET data were evaluated visually for the presence of malignancy and
      image quality. RESULTS: Both media caused significantly higher values for HU,
      SUV(mean) and SUV(max) for the enhanced PET/CT than the non-enhanced one (all
      p<0.01). There were no significant differences in the degree of increase of HU,
      SUV(mean) and SUV(max) between the two contrast media at any anatomic site (all
      p>0.05). Visual evaluation of lesions showed no differences between contrast and
      non-contrast PET/CT or between the two different contrast media (p=0.77).
      CONCLUSION: When using a constant iodine delivery rate and total iodine dose in a
      BSA adapted injection protocol, there are no quantitative or qualitative
      differences in either CT or PET between contrast media with an iodine
      concentration of 300 mg/ml and 370 mg/ml, respectively.

PMID- 24113434
TI  - Analysing exhaled breath during endovenous laser ablation of varicose veins using
      an electronic nose and gas chromatography-mass spectrometry.

PMID- 24113433
TI  - Bioinspired tilt-angle fabricated structure gradient fibers: micro-drops fast
      transport in a long-distance.
AB  - Issues of surfaces, e.g., inspired from beetle's back, spider silk, cactus stem,
      etc., become the active area of research on designing novel materials in need of
      human beings to acquire fresh water resource from air. However, the design of
      materials on surface structure is little achieved on controlling of micro-scale
      drop transport in a long distance. Here, we report the ability of micro-drop
      transport in a long distance on a bioinspired Fibers with Gradient Spindle-knots
      (BFGS), which are fabricated by tilt angle dip-coating method. The micro-drop of
      ~0.25 MUL transports in distance of ~5.00 mm, with velocity of 0.10-0.22 m s-1 on
      BFGS. It is attributed to the multi-level cooperation of the release energy of
      drop coalescence along the gradient spindle-knots, in addition to capillary
      adhesion force and continuous difference of Laplace pressure, accordingly, water
      drops are driven to move fast directionally in a long distance on BFGS.

PMID- 24113435
TI  - Triple signal amplification using gold nanoparticles, bienzyme and platinum
      nanoparticles functionalized graphene as enhancers for simultaneous multiple
      electrochemical immunoassay.
AB  - Here we demonstrated an ultrasensitive electrochemical immunoassay employing
      graphene, platinum nanoparticles (PtNPs), glucose oxidase (GOD) and horseradish
      peroxidase (HRP) as enhancers to simultaneously detect carcinoembryonic antigen
      (CEA) and alpha-fetoprotein (AFP). This immunosensor is based on the observation
      that multiple-labeled antibodies (thionine-labeled anti-CEA and ferrocene-labeled
      anti-AFP) recognition event yielded a distinct voltammetric peak through
      "sandwich" immunoreaction, whose position and size reflected the identity and
      level of the corresponding antigen. Greatly enhanced sensitivity for cancer
      markers is based on a triple signal amplification strategy. Experimental results
      revealed that the immunoassay enabled simultaneous determination of CEA and AFP
      in a single run with wide working ranges of 0.01-100 ng mL(-1). The detection
      limits reached 1.64 pg mL(-1) for CEA and 1.33 pg mL(-1) for AFP. No obvious
      cross-talk was observed during the experiment. In addition, through the analysis
      of clinical serum samples, the proposed method received a good correlation with
      ELISA as a reference. The signal amplification strategy could be easily modified
      and extended to detect other multiple targets.

PMID- 24113436
TI  - [A report on laboratory medicine in France].

PMID- 24113437
TI  - [Investigation of hyperhomocysteinemia].
AB  - Hyperhomocysteinemia has been described as a risk factor for venous and arterial
      thromboembolic diseases but may be also involved in neurodegenerative and
      neuropsychiatric disorders. Considering some arguments for homocysteine (Hcy)
      toxicity, a systematic investigation tool of hyperhomocysteinemia is needed.
      Understanding of the complexity of homocysteine metabolism can help to improve
      etiologic diagnosis of hyperhomocysteinemia, especially in determining the
      genetic or nutritional origin of the anomaly. We propose here a brief description
      of different clinical presentations and a strategy for biological investigation
      of hyperhomocysteinemia. 

PMID- 24113439
TI  - [Evaluation of (-2)proPSA in combination with total PSA and free PSA for the
      early detection of prostate cancer].
AB  - The analytical and clinical validation of new biomarkers for the early detection
      of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to
      calculate a standardized PHI index linked to a higher probability of a positive
      biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for
      prostate cancer diagnosis. The purpose of this study is to validate the
      analytical performance of the (-2)proPSA and to determine the predictive value of
      PHI for the early detection of prostate cancer. Analytical performances are
      correct. It is not necessary to dilute samples before analysis. The stability of
      (-2)proPSA is good until at least 3 hours at room temperature before
      centrifugation. The study of the PSAT, PSAL, (-2)proPSA and PHI values in a
      population of patients consulting for an early prostate cancer diagnosis shows
      that the index PHI is the most powerful predictive marker of cancer with an area
      under ROC curve of 0.70, whereas it is only 0.56 for total PSA. 

PMID- 24113438
TI  - [Anti-angiogenic therapies: from theory to practice].
AB  - During recent years clear progress has been made in support of tumor pathology.
      However, the treatment of metastatic disease is now a real therapeutic challenge.
      Among the new therapeutic strategies, blocking angiogenesis has been the subject
      of numerous clinical trials. However, if this approach was validated in 2004 by
      the approval of the first humanized anti-VEGF antibody (bevacizumab or
      Avastin((r)), Roche, 2004), the pre-clinical and clinical studies conducted in
      the last 5 years have moderated the enthusiasm that these therapies had led in
      the early 2000s. In November 2011, the US Food and drug administration (FDA)
      revoke the agency's approval of the breast cancer indication for Avastin((r))
      because of benefit-risk balance appears negative. This review describes
      successively the mechanisms of action of antiangiogenic agents, the main anti
      angiogenic drugs and the theoretical advantages and practical limitations of
      these therapies. 

PMID- 24113440
TI  - [Interest of the combination of high-sensitivity troponine and copeptin in
      diagnosis of non ST elevation myocardial infarction].
AB  - The diagnosis of non ST elevation myocardial infarction (NSTEMI) is very
      important for the emergency doctor. According to the literature copeptin, a
      marker of the endogenous stress, combined with troponin could be of interest in
      this diagnosis. The objective of the study was to investigate the association of
      high-sensitivity (HS) troponin and copeptine to eliminate the diagnosis of NSTEMI
      or unstable angina (UA) in patients arriving in Casualty with a thoracic pain.
      This prospective study included patients showing up at Casualty with a thoracic
      pain less than 12 hours old. Copeptin was measured by the BRAHMS method at
      admission and HS troponin was measured at admission, after 2 and 6 hours. The
      patients also had a follow-up phone call after 3 months. The study included 114
      patients with an average age of 54.6 years. NSTEMI was diagnosed for 8.8% of them
      and UA for 6.1%. The patients presenting NSTEMI or UA had a copeptin rate at
      admission higher than the others (24.7 pmol/L versus 7.1; p < 0.002). The
      negative predictive value of the association of HS troponin and copeptin was 95%
      whereas the sensitivity was 76.5% and the specificity 78.4%. The ROC curve
      analysis of the copeptin results brought to light a positivity limit which would
      have been more successful at 10.3 pmol/L than at 14.0. The association of
      copeptin and HS troponin can be useful to exclude the diagnosis of NSTEMI and
      favours faster treatment in Casualty. 

PMID- 24113441
TI  - Fifth international congress of the Federation of the European societies for
      Trace Elements and Minerals. Bridging between new advances and public health
      issues.

PMID- 24113442
TI  - [Interest of the study of a not identified peak on a hemoglobin chromatogram:
      delta variant or inter-sample contaminations?].
AB  - D-10((r)) (Bio-Rad) analyzer using cationic exchange high performance
      chromatography (HPLC) allows the detection of the main hemoglobin variants. This
      observation shows the presence of a peak on chromatogram with a low intensity and
      no quantifiable which can lead to different diagnosis. Inter-sample
      contaminations can be confused with the presence of an hemoglobin variant. This
      case highlights the importance of the knowledge of technicals limits for
      validation and clinical use of results. 

PMID- 24113443
TI  - [Association between multiple myeloma and acute myeloid leukemia secondary to
      myelodysplastic syndrome].
AB  - We report a rare case of association of two distinct hematologic malignancies:
      refractory cytopenia with multilineage dysplasia associated with del(5q) and
      symptomatic multiple myeloma associated with del(17p) and del(13q). After 16
      months, the patient presented an acute leukemic transformation of the
      myelodysplasic syndrome. 

PMID- 24113444
TI  - [A melanesian smile...].
AB  - We have detected an ovalo-stomatocytosis in a military 24-years-old man. We have
      sent a blood specimen to haematology laboratory in Kremlin-Bicetre (France) to
      test ektacytometry. The test concludes to an asymptomatic Melanesian
      ovalocytosis. 

PMID- 24113445
TI  - [Campylobacter fetus bacteremia complicating a dysenteric syndrome in a young
      epileptic].
AB  - Campylobacter fetus bacteremia is rare and occurs mainly in elderly and
      immunosuppressed patients. We report an original observation of C. fetus
      bacteremia complicating acute mucoid diarrhea in a young epileptic with no known
      risk factors. Our observation suggests that antiepileptic treatment could
      increase the risk of blood-borne of C. fetus infection. 

PMID- 24113446
TI  - [Extensive bone marrow necrosis and sickle cell disease].
AB  - A 24-years old Gabonese women with sickle cell disease had a severe vaso
      occlusive crisis, which was treated by exchange transfusion. Then, she developed
      an extended bone marrow necrosis and needed repeated blood transfusion. The aim
      of this article is to relate an rare sickle cell disease complication. 

PMID- 24113447
TI  - [Smartphone application for blood gas interpretation].
AB  - Ninety four per cent of health professionals use their smartphone for business
      purposes and more than 50% has medical applications. The "Blood Gas" application
      was created to be part of this dynamic and participate to e-health development in
      France. The "Blood Gas" application facilitates interpretation of the results of
      blood gas analysis using an algorithm developed with reference to a medical
      bibliography. It can detect some complex or intricate acid-base disorders in
      evaluating the effectiveness of the secondary response. The application also
      studied the respiratory status of the patient by calculating the PaO2/FiO2 ratio
      and the alveol-arterial gradient. It also indicates the presence of a shunt
      effect. Finally, a specific module to calculate the SID (strong ion difference)
      depending on the model of Stewart can detect complex acid-base disorders. 

PMID- 24113448
TI  - [Evaluation of high resolution Luminex technology for specific HLA-DRB1* typing
      in the Moroccan population].
AB  - The aim of this study is to evaluate the possibility of using routinely Luminex
      high definition technology for the specific HLA typing of donors and recipients
      of hematopoietic stem cells. 340 HLA-DRB1 *, all from Moroccan individuals were
      first tested at the generic level and then at the specific level by PCR-SSO
      Luminex high definition. Alleles identified correspond to those originally found
      with the generic typing. The specificity could be determined only in 41.5% of
      cases. The percentage of specific alleles identified for DRB1 * 04 was 78.7% and
      varies between 17.6% and 34.6% for other alleles. Of the eight haplotypes tested,
      blanks obtained by PCR-SSP were all resolved. Our results confirm the reliability
      of the method, since we confirm the alleles identified at the generic level.
      Luminex high definition technology can be used for HLA-DRB1 * 04 typing, and for
      the resolution of ambiguities and blanks. However, it must be completed by other
      techniques (PCR-SSP, SBT) in the context of hematopoietic stem cells. 

PMID- 24113449
TI  - [Method validation according to ISO 15189 and SH GTA 04: application for the
      detection of KRAS mutations using PCR TaqMan assay].
AB  - Since January 16(th) 2010, the French legislation requires that the medical
      laboratories must be accredited according to ISO 15189 standards. Thus, all
      medical laboratories in France must be accredited for at least part of their
      biological tests before the end of October 2013. Molecular biology tests are also
      concerned by the accreditation. Validation of molecular biology methods is made
      difficult, for reasons related to the methods, but also by the type of analytes
      that are basically rare. This article describes the validation of the qualitative
      detection of KRAS mutations in metastatic colorectal cancer using TaqMan PCR
      according to ISO 15189 and to the technical guide for accreditation in Human
      Health, SH-GTA-04, edited by the COFRAC. 

PMID- 24113450
TI  - [Method validation according to ISO 15189 and SH GTA 04: application for the
      extraction of DNA and its quantitative evaluation by a spectrophotometric assay].
AB  - According to the French legislation on medical biology (January 16th, 2010), all
      biological laboratories must be accredited according to ISO 15189 for at least
      50% of their activities before the end of 2016. The extraction of DNA from a
      sample of interest, whether solid or liquid is one of the critical steps in
      molecular biology and specifically in somatic or constitutional genetic. The
      extracted DNA must meet a number of criteria such quality and also be in
      sufficient concentration to allow molecular biology assays such as the detection
      of somatic mutations. This paper describes the validation of the extraction and
      purification of DNA using chromatographic column extraction and quantitative
      determination by spectrophotometric assay, according to ISO 15189 and the
      accreditation technical guide in Human Health SH-GTA-04. 

PMID- 24113451
TI  - [Internal audit in medical laboratory: what means of control for an effective
      audit process?].
AB  - To prepare the French Accreditation Committee (COFRAC) visit for initial
      certification of our medical laboratory, our direction evaluated its quality
      management system (QMS) and all its technical activities. This evaluation was
      performed owing an internal audit. This audit was outsourced. Auditors had an
      expertise in audit, a whole knowledge of biological standards and were
      independent. Several nonconformities were identified at that time, including a
      lack of control of several steps of the internal audit process. Hence, necessary
      corrective actions were taken in order to meet the requirements of standards, in
      particular, the formalization of all stages, from the audit program, to the
      implementation, review and follow-up of the corrective actions taken, and also
      the implementation of the resources needed to carry out audits in a pre
      established timing. To ensure an optimum control of each step, the main concepts
      of risk management were applied: process approach, root cause analysis, effects
      and criticality analysis (FMECA). After a critical analysis of our practices,
      this methodology allowed us to define our "internal audit" process, then to
      formalize it and to follow it up, with a whole documentary system. 

PMID- 24113452
TI  - [Diagnosis of a non-excretory myeloma].

PMID- 24113453
TI  - Hyperglycemia impairs atherosclerosis regression in mice.
AB  - Diabetic patients are known to be more susceptible to atherosclerosis and its
      associated cardiovascular complications. However, the effects of hyperglycemia on
      atherosclerosis regression remain unclear. We hypothesized that hyperglycemia
      impairs atherosclerosis regression by modulating the biological function of
      lesional macrophages. HypoE (Apoe(h/h)Mx1-Cre) mice express low levels of
      apolipoprotein E (apoE) and develop atherosclerosis when fed a high-fat diet.
      Atherosclerosis regression occurs in these mice upon plasma lipid lowering
      induced by a change in diet and the restoration of apoE expression. We examined
      the morphological characteristics of regressed lesions and assessed the
      biological function of lesional macrophages isolated with laser-capture
      microdissection in euglycemic and hyperglycemic HypoE mice. Hyperglycemia induced
      by streptozotocin treatment impaired lesion size reduction (36% versus 14%) and
      lipid loss (38% versus 26%) after the reversal of hyperlipidemia. However,
      decreases in lesional macrophage content and remodeling in both groups of mice
      were similar. Gene expression analysis revealed that hyperglycemia impaired
      cholesterol transport by modulating ATP-binding cassette A1, ATP-binding cassette
      G1, scavenger receptor class B family member (CD36), scavenger receptor class B1,
      and wound healing pathways in lesional macrophages during atherosclerosis
      regression. Hyperglycemia impairs both reduction in size and loss of lipids from
      atherosclerotic lesions upon plasma lipid lowering without significantly
      affecting the remodeling of the vascular wall.

PMID- 24113454
TI  - Bacterial infection increases periodontal bone loss in diabetic rats through
      enhanced apoptosis.
AB  - Periodontal disease is the most common osteolytic disease in humans and is
      significantly increased by diabetes mellitus. We tested the hypothesis that
      bacterial infection induces bone loss in diabetic animals through a mechanism
      that involves enhanced apoptosis. Type II diabetic rats were inoculated with
      Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor,
      ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL;
      osteoblasts and bone area were measured in H&E sections. New bone formation was
      assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels.
      Osteoclast number, eroded bone surface, and new bone formation were measured by
      tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed
      with an antibody against tumor necrosis factor-alpha. Bacterial infection doubled
      the number of tumor necrosis factor-alpha-expressing cells and increased
      apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase
      inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone
      surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly
      greater net bone area because of an increase in new bone formation, osteoblast
      numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic
      rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic
      cells that reduces osseous coupling through a caspase-3-dependent mechanism.

PMID- 24113456
TI  - PTGER1 deletion attenuates renal injury in diabetic mouse models.
AB  - We hypothesized that the EP1 receptor promotes renal damage in diabetic
      nephropathy. We rendered EP1 (PTGER1, official symbol) knockout mice (EP1(-/-))
      diabetic using the streptozotocin and OVE26 models. Albuminuria, mesangial matrix
      expansion, and glomerular hypertrophy were each blunted in EP1(-/-)
      streptozotocin and OVE26 cohorts compared with wild-type counterparts. Although
      diabetes-associated podocyte depletion was unaffected by EP1 deletion, EP1
      antagonism with ONO-8711 in cultured podocytes decreased angiotensin II-mediated
      superoxide generation, suggesting that EP1-associated injury of remaining
      podocytes in vivo could contribute to filtration barrier dysfunction.
      Accordingly, EP1 deletion in OVE26 mice prevented nephrin mRNA expression down
      regulation and ameliorated glomerular basement membrane thickening and foot
      process effacement. Moreover, EP1 deletion reduced diabetes-induced expression of
      fibrotic markers fibronectin and alpha-actin, whereas EP1 antagonism decreased
      fibronectin in cultured proximal tubule cells. Similarly, proximal tubule megalin
      expression was reduced by diabetes but was preserved in EP1(-/-) mice. Finally,
      the diabetes-associated increase in angiotensin II-mediated constriction of
      isolated mesenteric arteries was blunted in OVE26EP1(-/-) mice, demonstrating a
      role for EP1 receptors in the diabetic vasculature. These data suggest that EP1
      activation contributes to diabetic nephropathy progression at several locations,
      including podocytes, proximal tubule, and the vasculature. The EP1 receptor
      facilitates the actions of angiotensin II, thereby suggesting that targeting of
      both the renin-angiotensin system and the EP1 receptor could be beneficial in
      diabetic nephropathy.

PMID- 24113455
TI  - Hepatic loss of miR-122 predisposes mice to hepatobiliary cyst and hepatocellular
      carcinoma upon diethylnitrosamine exposure.
AB  - Loss of miR-122 causes chronic steatohepatitis and spontaneous hepatocellular
      carcinoma. However, the consequence of miR-122 deficiency on genotoxic stress
      induced liver pathogenesis is poorly understood. Here, we investigated the impact
      of miR-122 depletion on liver pathobiology by treating liver-specific miR-122
      knockout (LKO) mice with the hepatocarcinogen diethylnitrosamine (DEN). At 25
      weeks post-DEN injection, all LKO mice developed CK-19-positive hepatobiliary
      cysts, which correlated with DEN-induced transcriptional activation of Cdc25a
      mediated through E2f1. Additionally, LKO livers were more fibrotic and vascular,
      and developed larger microscopic tumors, possibly due to elevation of the Axl
      oncogene, a receptor tyrosine kinase as a novel target of miR-122, and several
      protumorigenic miR-122 targets. At 35 weeks following DEN exposure, LKO mice
      exhibited a higher incidence of macroscopic liver tumors (71%) and cysts (86%)
      compared to a 21.4% and 0% incidence of tumors and cysts, respectively, in
      control mice. The tumors in LKO mice were bigger (ninefold, P = 0.015) and
      predominantly hepatocellular carcinoma, whereas control mice mostly developed
      hepatocellular adenoma. DEN treatment also reduced survival of LKO mice compared
      to control mice (P = 0.03). Interestingly, induction of oxidative stress and
      proinflammatory cytokines in LKO liver shortly after DEN exposure indicates
      predisposition of a pro-tumorigenic microenvironment. Collectively, miR-122
      depletion facilitates cystogenesis and hepatocarcinogenesis in mice on DEN
      challenge by up-regulating several genes involved in proliferation, growth factor
      signaling, neovascularization, and metastasis.

PMID- 24113457
TI  - TRPC4 inactivation confers a survival benefit in severe pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary
      arterial pressure with lumen-occluding neointimal and plexiform lesions.
      Activation of store-operated calcium entry channels promotes contraction and
      proliferation of lung vascular cells. TRPC4 is a ubiquitously expressed store
      operated calcium entry channel, but its role in PAH is unknown. We tested the
      hypothesis that TRPC4 promotes pulmonary arterial constriction and occlusive
      remodeling, leading to right ventricular failure in severe PAH. Severe PAH was
      induced in Sprague-Dawley rats and in wild-type and TRPC4-knockout Fischer 344
      rats by a single subcutaneous injection of SU5416 [SU (semaxanib)], followed by
      hypoxia exposure (Hx; 10% O2) for 3 weeks and then a return to normoxia (Nx; 21%
      O2) for 3 to 10 additional weeks (SU/Hx/Nx). Although rats of both backgrounds
      exhibited indistinguishable pulmonary hypertensive responses to SU/Hx/Nx, Fischer
      344 rats died within 6 to 8 weeks. Normoxic and hypertensive TRPC4-knockout rats
      recorded hemodynamic parameters similar to those of their wild-type littermates.
      However, TRPC4 inactivation conferred a striking survival benefit, due in part to
      preservation of cardiac output. Histological grading of vascular lesions revealed
      a reduction in the density of severely occluded small pulmonary arteries and in
      the number of plexiform lesions in TRPC4-knockout rats. TRPC4 inactivation
      therefore provides a survival benefit in severe PAH, associated with a decrease
      in the magnitude of occlusive remodeling.

PMID- 24113458
TI  - Whole-genome methylation sequencing reveals distinct impact of differential
      methylations on gene transcription in prostate cancer.
AB  - DNA methylation is one of the most important epigenetic mechanisms in regulating
      gene expression. Genome hypermethylation has been proposed as a critical
      mechanism in human malignancies. However, whole-genome quantification of DNA
      methylation of human malignancies has rarely been investigated, and the
      significance of the genome distribution of CpG methylation is unclear. We
      performed whole-genome methylation sequencing to investigate the methylation
      profiles of 13 prostate samples: 5 prostate cancers, 4 matched benign prostate
      tissues adjacent to tumor, and 4 age-matched organ-donor prostate tissues.
      Alterations of methylation patterns occurred in prostate cancer and in benign
      prostate tissues adjacent to tumor, in comparison with age-matched organ-donor
      prostates. More than 95% alterations of genome methylation occurred in sequences
      outside CpG islands. Only a small fraction of the methylated CpG islands had any
      effect on RNA expression. Both intragene and promoter CpG island methylations
      negatively affected gene expression. However, suppressions of RNA expression did
      not correlate with levels of CpG island methylation, suggesting that CpG island
      methylation alone might not be sufficient to shut down gene expression. Motif
      analysis revealed a consensus sequence containing Sp1 binding motif significantly
      enriched in the effective CpG islands.

PMID- 24113459
TI  - Brucella abortus induces collagen deposition and MMP-9 down-modulation in hepatic
      stellate cells via TGF-beta1 production.
AB  - In patients with active brucellosis, the liver is frequently affected by
      histopathologic lesions, such as granulomas, inflammatory infiltrations, and
      parenchymal necrosis. Herein, we examine some potential mechanisms of liver
      damage in brucellosis. We demonstrate that Brucella abortus infection inhibits
      matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and
      tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic
      stellate cells (LX-2). These phenomena depend on transforming growth factor-beta1
      induction. In contrast, supernatants from B. abortus-infected hepatocytes and
      monocytes induce MMP-9 secretion and inhibit collagen deposition in hepatic
      stellate cells. Yet, if LX-2 cells are infected with B. abortus, the capacity of
      supernatants from B. abortus-infected hepatocytes and monocytes to induce MMP-9
      secretion and inhibit collagen deposition is abrogated. These results indicate
      that depending on the balance between interacting cells and cytokines of the
      surrounding milieu, the response of LX-2 cells could be turned into an
      inflammatory or fibrogenic phenotype. Livers from mice infected with B. abortus
      displayed a fibrogenic phenotype with patches of collagen deposition and
      transforming growth factor-beta1 induction. This study provides potential
      mechanisms of liver immune response induced by B. abortus-infected hepatic
      stellate cells. In addition, these results demonstrate that the cross talk of
      these cells with hepatocytes and macrophages implements a series of interactions
      that may contribute to explaining some of mechanisms of liver damage observed in
      human brucellosis.

PMID- 24113460
TI  - Management of corneal decompensation 4 decades after Sputnik intraocular lens
      implantation.
AB  - OBJECTIVES: We report an unusual case of corneal decompensation occurring four
      decades after complicated cataract extraction with implantation of a Sputnik
      intraocular lens (IOL) and highlight the clinical and practical issues faced in
      managing corneal decompensation with a Sputnik IOL. METHODS: A 72-year-old woman
      presented with deterioration of the vision in her left eye, four decades after
      intracapsular cataract extraction with Sputnik IOL implantation. Ocular
      examination revealed diffuse corneal edema and thickened vitreous strands in the
      anterior chamber. Her best-corrected visual acuity (BCVA) worsened to 6/60 within
      3 months. Anterior vitrectomy and inferior iridectomy combined with Descemet
      stripping automated endothelial keratoplasty was performed. RESULTS: The
      procedure was successful, with the patient achieving best-corrected visual acuity
      of 6/6 at 8 months postoperatively. CONCLUSION: Corneal decompensation after
      Sputnik IOL implantation can occur four decades later. When the historical
      preoperative visual acuity is good in such cases, careful anterior vitrectomy
      with Descemet-stripping automated endothelial keratoplasty provides good visual
      rehabilitation.

PMID- 24113461
TI  - Effects of corneal collagen crosslinking on corneal topographic indices in
      patients with keratoconus.
AB  - OBJECTIVES: To evaluate the effects of corneal crosslinking (CXL) on corneal
      topographic indices in patients with progressive keratoconus using Scheimpflug
      imaging system. METHODS: This retrospective study comprised 59 eyes of 47
      patients who underwent CXL treatment for confirmed progressive keratoconus.
      Changes in corrected distance visual acuity (CDVA, logMAR equivalent), maximum
      keratometry (K), and corneal topographic indices included index of surface
      variance (ISV), index of vertical asymmetry, keratoconus index, center
      keratoconus index (CKI), index of height asymmetry (IHA), index of height
      decentration, and minimum radius of curvature (Rmin) were analyzed at 1-year
      follow-up. Correlations between topographic indices and visual acuity were
      sought. RESULTS: The study included 59 eyes of 47 patients with progressive
      keratoconus. The mean CDVA (P<0.001), maximum K (P<0.001), ISV, Rmin, and CKI (P
      =0.013, P < 0.001, respectively) significantly improved after CXL treatment.
      Moreover, we found a significant negative correlation between the change in IHA
      value and the improvement in CDVA (r = -0.351; P = 0.006). CONCLUSIONS: In
      patients with progressive keratoconus, cornea becomes more optically regular
      after CXL treatment. Changes in topographic indices might be valuable to follow
      up the normalization of keratoconic cornea during the postoperative course and
      superior-inferior height symmetry seems to be associated with visual improvement.

PMID- 24113462
TI  - Contact lens care solutions downregulate membrane-associated mucins 1 and 16 in
      cultured human corneal epithelial cells and at the rat corneal surface in vivo.
AB  - OBJECTIVE: The purpose of this study was first to evaluate the effect of
      multipurpose contact lens care solutions (MPSs) on the expression of membrane
      associated mucins (MUC1 and MUC16) in SV40-transformed human corneal epithelial
      (HCE-T) cells and in vivo rat cornea. The second aim of this study was to
      determine the role of the common MPS additive boric acid in reducing mucin
      expression and release. METHODS: The HCE-T cells were exposed to different
      concentrations of MPS-F, MPS-G, MPS-H, MPS-I, and MPS-J with 100% treatment for
      30 minutes and 10% treatment for 24 hours. MUC1 and MUC16 expressions were
      subsequently analyzed by Western blotting. Wister rats were also subjected to MPS
      A, MPS-B, MPS-C, MPS-D, and MPS-E and received phosphate-buffered saline exposure
      (1 drop in the right eye every 10 minutes for 1 hour). The left eye was used as
      control. Cornea sections and lysates were used for the immunohistochemical assay
      of MUC1 and MUC16 expressions. Conditioned media from treated HCE-T cells were
      also analyzed using Western blotting. RESULTS: The MPSs containing boric acid
      downregulated MUC1 and MUC16 in the rat cornea, whereas MPSs without boric acid
      had no effect as demonstrated by the Western blotting and immunohistochemical
      analysis. Conditioned media from MPS-containing boric acid revealed some trace of
      MUC16. CONCLUSIONS: The clinical use of MPSs containing boric acid that reduce
      MUC1 and MUC16 availability should be avoided. Additionally, the presence of
      MUC16 in the conditioned media suggests that boric acid may have enhanced
      cleavage of MUC16 at the cell membrane surface.

PMID- 24113463
TI  - Infectious crystalline keratopathy caused by Pseudomonas fluorescens.
AB  - OBJECTIVE: To demonstrate a case of infectious crystalline keratopathy (ICK)
      caused by Pseudomonas fluoresecens (PF). METHODS: Case report description.
      RESULTS: A 15-year-old female contact lens wearer presented complaining of eye
      pain and redness in the left eye. The patient reported that she had suffered a
      corneal scratch a few months earlier, which was treated by her family physician,
      and that she had felt some discomfort since then. The biomicroscopy showed a
      central corneal abscess with a crystalline appearance, stromal edema, the Tyndall
      effect, and abundant fibrin in the anterior chamber. A diagnosis of ICK was made.
      The culture was positive for gram-negative PF. Pseudomonas fluoresecens was
      sensitive to cephalosporins, quinolones, and tobramycin. CONCLUSIONS: No cases of
      ICK caused by PF have been reported previously. Two previous studies reported
      that the gram-negative Pseudomonas aeruginosa caused ICK. Unlike other ICK cases
      in which there is minimal stromal inflammation, the patient presented with an
      intense inflammatory reaction in the anterior chamber.

PMID- 24113464
TI  - DNA extraction and a cost-effective detection method for Echinococcus granulosus
      protoscoleces.
AB  - Most methods of DNA purification from protoscoleces of Echinococcus granulosus
      involve the use of expensive kits and may also require a second step after
      extraction for an effective purification. The present work describes an optimized
      cost-effective method that is fast and simple. This method is based on a chemical
      lysis with proteinase K with a subsequent one-step PCR detection. In this study
      we used already available primers and newly designed primers to amplify two
      fragments of different size corresponding to the mitochondrial cytochrome C
      oxidase subunit 1 gene. By one-step PCR, both fragments were successfully
      amplified from even a single protoscolex. This result demonstrates that this
      method of extraction is efficient even with small amounts of sample and that PCR
      is highly sensitive. The major advantage of this lysis-PCR method is that it
      avoids a second step of purification resulting in a simpler and more economical
      method. Our research will serve as a base for future studies on E. granulosus
      genotyping, mainly with wild mammals with a low number of cysts. 

PMID- 24113465
TI  - Ascaridia galli infection affects pullets differently when feed is contaminated
      with the Fusarium toxin deoxynivalenol (DON).
AB  - The Fusarium mycotoxin deoxynivalenol (DON) is a common contaminant of cereal
      grains used as animal feed. DON is known for its cytotoxic and anti-proliferative
      properties and might adversely affect the health of poultry. The prevalence of
      the intestinal parasitizing roundworm Ascaridia galli is higher in outdoor
      housing systems and has been associated with maldigestion and malabsorption. It
      was hypothesized that ingested DON might not only affect the pullet itself but
      could also act on the nematode parasitizing in the ingesta. To examine these
      interactions between A. galli infection and DON contamination of feed 4 groups of
      9 pullets in each were tested; non-infected groups were fed either an
      uncontaminated control (CON-) or a Fusarium toxin contaminated and mainly DON
      containing diet (FUS-), and the corresponding A. galli inoculated groups were fed
      accordingly (CON+, FUS+). A. galli infection significantly reduced the jejunal
      villi height and increased the thickness of the tunica muscularis with the effect
      being more pronounced when the DON-containing diet was fed (Group FUS+). Only in
      this group significantly increased weights of jejunal and ileal tissues and of
      livers were noticed. Moreover, DON was detected in plasma of the pullets at
      higher frequencies when they were infected suggesting a facilitated absorption of
      DON. Group FUS+ was characterized by a significantly higher excretion of A. galli
      eggs and a concomitant lower proportion of pullets with detectable antibodies
      against a somatic antigen of A. galli while worm burden and worm characteristics
      were not affected by diet. Other effects of feeding the FUS diet to the infected
      pullets included an increased mass per length of male worms. In conclusion,
      infection of pullets with A. galli might increase the susceptibility towards DON
      as indicated by an increased DON absorption rate and a compromised antibody
      formation. The effects of DON on fecundity and worm morphology require further
      examination.

PMID- 24113466
TI  - Solar ultraviolet radiation response of EBT2 Gafchromic, radiochromic film.
AB  - Measurement of solar ultraviolet (UV) radiation is an important aspect of
      dosimetry for the improved knowledge of UV exposure and its associated health
      related issues. EBT2 Gafchromic film has been designed by its manufacturers as an
      improved tool for ionizing radiation dosimetry. The film is stated as exhibiting
      a significant reduction in UV response. However, results have shown that when
      exposed to UV from the 'bottom side' i.e. from the thick laminate side, the film
      exhibits a sensitivity to solar UV radiation which is both measurable and
      accurate for UV dosimetry. Films were irradiated in this position to known solar
      UV exposures and results are quantified showing a reproducibility of measurement
      to within +/-7% (1 SD) when compared to calibrated UV meters. With an exposure of
      20 J cm(-2) broad spectrum solar UV, the films net OD change was found to be
      0.248 OD +/- 0.021 OD when analysing the results using the red channel region of
      an Epson V700 desktop scanner. This was compared to 0.0294 OD +/- 0.0053 OD
      change with exposure to the same UV exposure from the top side. This means that
      solar UV dosimetry can be performed using EBT2 Gafchromic film utilizing the
      underside of the film for dosimetry. The main advantages of this film type for
      measurement of UV exposure is the visible colour change and thus easy analysis
      using a desktop scanner as well as its uniformity in response and its robust
      physical strength for use in outside exposure situations. 

PMID- 24113467
TI  - Radiation dose reduction in paranasal sinus CT using model-based iterative
      reconstruction.
AB  - BACKGROUND AND PURPOSE: CT performed with Veo model-based iterative
      reconstruction has shown the potential for radiation-dose reduction. This study
      sought to determine whether Veo could reduce noise and improve the image quality
      of low-dose sinus CT. MATERIALS AND METHODS: Twenty patients consented to
      participate and underwent low- and standard-dose sinus CT on the same day.
      Standard-dose CT was created with filtered back-projection (120 kV[peak], 210 mA,
      0.4-second rotation, and 0.531 pitch). For low-dose CT, mA was decreased to 20
      (the remaining parameters were unchanged), and images were generated with
      filtered back-projection and Veo. Standard- and low-dose datasets were
      reconstructed by using bone and soft-tissue algorithms, while the low-dose Veo
      reconstruction only had a standard kernel. Two blinded neuroradiologists
      independently evaluated the image quality of multiple osseous and soft-tissue
      craniofacial structures. Image noise was measured by using multiple regions of
      interest. RESULTS: Eight women and 12 men (mean age, 63.3 years) participated.
      Volume CT dose indices were 2.9 mGy (low dose) and 31.6 mGy (standard dose), and
      mean dose-length products were 37.4 mGy-cm (low dose) and 406.1 mGy-cm (standard
      dose). Of all the imaging series, low-dose Veo demonstrated the least noise (P <
      .001). Compared with filtered back-projection low-dose CT using soft-tissue and
      bone algorithms, Veo had the best soft-tissue image quality but the poorest bone
      image quality (P < .001). CONCLUSIONS: Veo significantly reduces noise in low
      dose sinus CT. Although this reduction improves soft-tissue evaluation, thin bone
      becomes less distinct.

PMID- 24113468
TI  - Predators and cranks.

PMID- 24113469
TI  - An exponential growth in incidence of thyroid cancer: trends and impact of CT
      imaging.
AB  - BACKGROUND AND PURPOSE: Workup of incidental thyroid nodules detected on CT
      imaging could be contributing to the increased diagnosis of small thyroid
      cancers. The purpose of this study was to evaluate recent trends in the incidence
      of thyroid cancer, and to determine the relationship between annual CT imaging
      volume and rate of thyroid cancer diagnosis. MATERIALS AND METHODS: This
      retrospective cohort study used data bases for thyroid cancer and CT imaging
      volume. Thyroid cancer data from 1983-2009 were obtained from the Surveillance,
      Epidemiology, and End Results data base. National Council of Radiation Protection
      and Measurements Report No. 160 provided data on hospital and nonhospital CT
      imaging volume for 1993-2006. Trends in thyroid cancer were modeled for overall
      incidence on the basis of patient age, tumor histologic features, and tumor size
      and stage. Linear regression analysis was performed to evaluate the strength of
      the relationship between annual CT scan volume and the incidence of thyroid
      cancer by tumor size and histologic type. RESULTS: In 2009, the incidence of
      thyroid cancer was 14 per 100,000, which represented a 1.9-fold increase compared
      with 2000. The growth in incidence was exponential compared with a minimal linear
      increase in thyroid cancer mortality rate. The subgroup with the greatest change
      was subcentimeter papillary carcinoma, with doubling in incidence approximately
      every 6.2 years. The linear relationship between annual CT scan volume and the
      incidence of subcentimeter papillary carcinoma was very strong (R(2) = 0.98; P <
      .0001). CONCLUSIONS: The incidence of subcentimeter papillary carcinoma is
      growing at an exponential rate without significant change in mortality rate. The
      strong linear relationship between new cases of subcentimeter papillary
      carcinomas and the number of CT scans per year suggests that an increase in CT
      scans may increase the detection of incidental thyroid cancers.

PMID- 24113470
TI  - Frontotemporal cortical thinning in amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging
      techniques has undoubtedly improved our knowledge of the pathophysiology of
      amyotrophic lateral sclerosis. Nevertheless, the precise extent of
      neurodegeneration throughout the central nervous system is not fully understood.
      In the present study, we assessed the spatial distribution of cortical damage in
      amyotrophic lateral sclerosis by using a cortical thickness measurement approach.
      MATERIALS AND METHODS: Surface-based morphometry was performed on 20 patients
      with amyotrophic lateral sclerosis and 18 age- and sex-matched healthy control
      participants. Clinical scores of disability and disease progression were
      correlated with measures of cortical thickness. RESULTS: The patients with
      amyotrophic lateral sclerosis showed a significant cortical thinning in multiple
      motor and extramotor cortical areas when compared with healthy control
      participants. Gray matter loss was significantly related to disease disability in
      the left lateral orbitofrontal cortex (P = .04), to disease duration in the right
      premotor cortex (P = .007), and to disease progression rate in the left
      parahippocampal cortex (P = .03). CONCLUSIONS: Cortical thinning of the motor
      cortex might reflect upper motor neuron impairment, whereas the extramotor
      involvement seems to be related to disease disability, progression, and duration.
      The cortical pattern of neurodegeneration depicted resembles what has already
      been described in frontotemporal dementia, thereby providing further structural
      evidence of a continuum between amyotrophic lateral sclerosis and frontotemporal
      dementia.

PMID- 24113471
TI  - Toward patient-tailored perfusion thresholds for prediction of stroke outcome.
AB  - BACKGROUND AND PURPOSE: Multiple patient-specific clinical and radiologic
      parameters impact traditional perfusion thresholds used to classify/determine
      tissue outcome. We sought to determine whether modified baseline perfusion
      thresholds calculated by integrating baseline perfusion and clinical factors
      better predict tissue fate and clinical outcome. MATERIALS AND METHODS: CTP
      within 4.5 hours of acute anterior circulation stroke onset and 5- to 7-day MR
      imaging were performed for 203 patients with stroke, divided into derivation (n =
      114) and validation (n = 89) data bases. Affected regions were operationally
      classified as infarct and noninfarct according to baseline CTP and follow-up
      FLAIR imaging. Perfusion thresholds were derived for each of the infarct and
      noninfarct regions, without and with transformation by baseline clinical and
      radiologic variables by using a general linear mixed model. Performance of
      transformed and nontransformed perfusion thresholds for tissue fate and 90-day
      clinical outcome prediction was then tested in the derivation data base.
      Reproducibility of models was verified by using bootstrapping and validated in an
      independent cohort. RESULTS: Perfusion threshold transformation by clinical and
      radiologic baseline parameters significantly improved tissue fate prediction for
      both gray matter and white matter (P < .001). Transformed thresholds improved the
      90-day outcome prediction for CBF and time-to-maximum (P < .001). Transformed
      relative CBF and absolute time-to-maximum values demonstrated maximal GM and WM
      accuracies in the derivation and validation cohorts (relative CBF GM: 91%, 86%;
      WM: 86%, 83%; absolute time-to-maximum 88%, 79%, and 80%, 76% respectively).
      CONCLUSIONS: Transformation of baseline perfusion parameters by patient-specific
      clinical and radiologic parameters significantly improves the accuracy of tissue
      fate and clinical outcome prediction.

PMID- 24113473
TI  - Discharge of perfluorinated compounds from rivers and their influence on the
      coastal seas of Hyogo prefecture, Japan.
AB  - The aim of this study was to investigate 12 perfluorinated compounds (PFCs)
      including perfluorinated carboxylates (C4-C12) and perfluorinated alkyl
      sulfonates (C4, C6, and C8) in river and seawater samples to determine
      contamination levels in the aquatic environment of Hyogo prefecture, Japan. High
      levels of perfluorohexanoic acid (PFHxA; 2300-16,000 ng/L) were detected in the
      Samondogawa River at Tatsumi Bridge downstream of a PFC production facility; this
      location also had the highest mass flow rate of PFCs (3900-29,000 kg/y).
      Widespread contamination of coastal waters was confirmed with PFHxA as the
      dominant compound. Perfluorooctanoic acid was also prevalent in coastal waters.
      The concentration of PFHxA in coastal seawater and the distance from the mouth of
      the Samondogawa River were inversely related. This discharge of high
      concentrations of PFHxA from the Samondogawa River may have affected
      concentrations of PFCs in Osaka Bay. 

PMID- 24113472
TI  - SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88,
      XPO1 and TP53 in 1160 untreated CLL patients.
AB  - We analyzed a large cohort of 1160 untreated CLL patients for novel genetic
      markers (SF3B1, NOTCH1, FBXW7, MYD88, XPO1) in the context of molecular,
      immunophenotypic and cytogenetic data. NOTCH1 mutations (mut) (12.3%), SF3B1mut
      (9.0%) and TP53mut (7.1%) were more frequent than XPO1mut (3.4%), FBXW7mut (2.5%)
      and MYD88mut (1.5%). SF3B1mut, NOTCH1mut, TP53mut and XPO1mut were highly
      correlated to unmutated, whereas MYD88mut were associated with mutated IGHV
      status. Associations of diverse cytogenetic aberrations and mutations emerged:
      (1) SF3B1mut with del(11q), (2) NOTCH1mut and FBXW7mut with trisomy 12 and nearly
      exclusiveness of SF3B1mut, (3) MYD88mut with del(13q) sole and low frequencies of
      SF3B1mut, NOTCH1mut and FBXW7mut. In patients with normal karyotype only SF3B1mut
      were frequent, whereas NOTCH1mut rarely occurred. An adverse prognostic impact on
      time to treatment (TTT) and overall survival (OS) was observed for SF3B1mut,
      NOTCH1mut and TP53 disruption. In multivariate analyses SF3B1mut, IGHV mutational
      status and del(11q) were the only independent genetic markers for TTT, whereas
      for OS SF3B1mut, IGHV mutational status and TP53 disruption presented with
      significant impact. Finally, our data suggest that analysis of gene mutations
      refines the risk stratification of cytogenetic prognostic subgroups and confirms
      data of a recently proposed model integrating molecular and cytogenetic data. 

PMID- 24113474
TI  - Characterization of polybrominated diphenyl ethers (PBDEs) and hydroxylated and
      methoxylated PBDEs in soils and plants from an e-waste area, China.
AB  - In order to characterize polybrominated diphenyl ethers (PBDEs), and hydroxylated
      and methoxylated PBDEs (OH-PBDEs and MeO-PBDEs) in the soil-plant system, soil
      and plant samples were collected from an e-waste recycling area in China. Forty
      one PBDEs, twelve OH-PBDEs and MeO-PBDEs were detected in the soil and plant
      samples. Concentrations of PBDEs in roots were significantly correlated to their
      concentrations in the soils, but the percentages of lower brominated congeners in
      the plants were higher than those in the soils. Significant positive linear
      relationships exist between concentrations of ?OH-PBDEs and ?MeO-PBDEs with
      higher levels of ?MeO-PBDEs than those of ?OH-PBDEs in the soils, plant roots and
      leaves. A majority of the OH-/MeO-PBDEs had the hydroxyl or methoxy group at the
      ortho-positions to the biphenyl bond for most of the plant species. However the
      occurrence of meta- and para- substituted OH-/MeO-PBDEs in soils and plants were
      also confirmed. 

PMID- 24113475
TI  - Procalcitonin as a reliable biomarker in acute coronary syndromes: what is its
      role?

PMID- 24113476
TI  - Endoscopic removal of pharmacobezoar in case of intentional potassium overdose.
AB  - BACKGROUND: Hyperkalemia is a potentially life-threatening electrolyte
      abnormality commonly seen in the emergency department (ED). Intentional overdose
      of potassium supplements is an uncommon occurrence. OBJECTIVE: This case
      illustrates a novel approach to treatment of pharmacobezoar with
      esophagogastroduodenoscopy (EGD) and demonstrates its effectiveness in the
      setting of extended-release potassium chloride overdose. CASE REPORT: A 44-year
      old female presented to the ED with intentional ingestion of an unknown amount of
      extended-release potassium chloride (K-Dur(r)) tablets and alprazolam (Xanax(r)).
      The patient's serum potassium was initially 7.3 mmol/L and she was treated with
      standard treatments, including albuterol, calcium gluconate, insulin, dextrose,
      and sodium bicarbonate. Radiographic investigation showed a pharmacobezoar in the
      gastric fundus. Treatment was then augmented with whole bowel irrigation (WBI)
      using polyethylene glycol solution via nasogastric tube. Patient did not tolerate
      the nasogastric tube, became combative with increasing alteration in her level of
      consciousness, and WBI therapy was stopped. After discussion with the
      gastroenterologist, the patient was treated with EGD to remove the
      pharmacobezoar. The EGD was successful in the removal of the pharmacobezoar and
      the patient's potassium normalized without complications. CONCLUSIONS: We
      recommend that in cases of suspected or confirmed potassium drug bezoar in the
      stomach, physicians consider EGD for removal. This allows for normalization of
      potassium level while preventing adverse sequelae.

PMID- 24113477
TI  - Acute appendicitis: investigating an optimal outer appendiceal diameter cut-point
      in a pediatric population.
AB  - BACKGROUND: Acute appendicitis is the most common cause of abdominal pain in
      children requiring operative intervention. Among a number of sonographic criteria
      to aid in the diagnosis of appendicitis, an outer diameter >6 mm is the most
      objective and widely accepted. However, there is a lack of evidence-based
      standards governing this consensus. STUDY OBJECTIVES: The aim of this study was
      to determine the outer appendiceal diameter that maximizes sensitivity and
      specificity in a pediatric population. METHODS: A retrospective review of all
      urgent diagnostic ultrasounds (US) was performed over 2 years in children aged
      <18 years. The diagnostic accuracy of various cut-points was assessed by
      calculating the sensitivity and specificity and plotting a receiver operating
      characteristic (ROC) curve. RESULTS: The study sample consisted of 398 patients
      in whom the appendix was visualized on US. The median outer appendiceal diameter
      was significantly higher in the surgical group compared to the nonsurgical group
      (9.4 mm; range = 8.1-12.0 vs. 5.5 mm; range = 4.4-6.5, p < 0.01). The optimal cut
      point with the greatest area under the ROC curve was determined to be an outer
      appendiceal diameter of 7.0 mm. CONCLUSIONS: In our patients, adopting a 7-mm
      rather than a 6-mm appendiceal diameter threshold would balance a greater number
      of missed cases of acute appendicitis for a reduction in the number of
      unnecessary surgeries.

PMID- 24113478
TI  - The heat is on... thermal epiglottitis as a late presentation of airway steam
      injury.
AB  - BACKGROUND: Thermal epiglottitis is a rare but potentially life-threatening
      disease. Diagnosis requires a thorough history and high clinical level of
      suspicion, particularly in children. Thermal epiglottitis from steam inhalation
      can have a slow onset without oropharyngeal signs of thermal injury, findings
      that can hide the clinical diagnosis. OBJECTIVE: Our aim was to review the
      pathophysiology and clinical presentation of thermal epiglottitis and the
      challenges involved in diagnosis and management of this form of atypical
      epiglottitis. CASE REPORT: We describe the case of a 22-month-old male presenting
      to the pediatric emergency department after a scald burn from steam and boiling
      water resulting in 12% body surface area burns to his chin, chest, and shoulder,
      with no obvious oropharyngeal or neck injuries. At the time of presentation, he
      was afebrile and well appearing. Six hours after the injury, he was sitting in
      the "tripod position," drooling, with pooled saliva in his mouth and inspiratory
      stridor. Intubation in the operating room using conventional direct laryngoscopy
      was not successful and he was intubated using an operative endoscope.
      Laryngoscopy demonstrated thermal epiglottitis. A tracheostomy was performed to
      secure the airway, and he was admitted to the pediatric intensive care unit. He
      was discharged home and decannulated 4 weeks later, when airway endoscopy showed
      complete recovery with normal airway structures. CONCLUSION: A thorough history
      and physical examination together with a high level of suspicion and aggressive,
      collaborative airway management is vital in preventing catastrophic airway
      obstruction in atypical forms of epiglottitis.

PMID- 24113479
TI  - Radiolucent circular line in pelvis on plain x-rays.

PMID- 24113480
TI  - Ultrasound exposure during gross anatomy.
AB  - BACKGROUND: As medical schools seek to standardize ultrasound training and
      incorporate clinical correlations into the basic science years, we proposed that
      ultrasonography should have a greater role in the anatomy curriculum. OBJECTIVES:
      To describe the introduction of ultrasound into the curriculum of a first-year
      medical student anatomy course and evaluate the utility of this introduction.
      METHODS: First-year medical students attended two ultrasound lectures and three
      small-group hands-on sessions that focused on selected aspects of
      musculoskeletal, thoracic, abdominal, and neck anatomy. Pre and post surveys were
      administered to assess student perception of their ability to obtain and
      interpret ultrasound images and the utility of ultrasound in the anatomy course.
      Understanding of basic ultrasound techniques and imaging was tested in the
      practical examinations. RESULTS: Of the 269 first-year medical students who
      completed the course, 144 students completed both surveys entirely, with a
      response rate of 53%. Students' interest and self-perceived experience, comfort,
      and confidence in ultrasound skills significantly increased (p < 0.001) as a
      result of this early introduction to ultrasonography. Objective evidence,
      provided by practical examination scores on ultrasound images, is consistent with
      this self-perceived confidence reported by students. CONCLUSIONS: Ultrasound can
      be effectively incorporated into an anatomy course for first-year medical
      students by utilizing didactics and hands-on exposure. Medical students found the
      addition of ultrasound training to be valuable, not only in enhancing their
      understanding of anatomy, but also in increasing their interest and experience in
      ultrasound imaging.

PMID- 24113481
TI  - Lead toxicity as an etiology for abdominal pain in the emergency department.
AB  - BACKGROUND: Abdominal pain is an uncommon presentation of lead toxicity in the
      emergency department (ED). However, making the diagnosis is important in avoiding
      unnecessary testing and the long-term sequelae of lead toxicity. OBJECTIVES: To
      illustrate possible presentations of abdominal pain secondary to lead toxicity
      and highlight the importance of taking a thorough patient history. CASE REPORT:
      We report 2 patients who presented to the ED with abdominal pain and underwent
      extensive evaluations that did not reveal an etiology. At follow-up visits, their
      occupational histories revealed possible lead exposures from working for a bullet
      recycling company. Tests revealed that each patient had extremely high lead
      levels and they were both treated for lead toxicity. Their abdominal pain
      resolved as their lead levels decreased. CONCLUSION: These cases demonstrate a
      rare but significant cause of abdominal pain in the ED. Although history-taking
      in the ED is necessarily brief, these cases underscore the importance of
      obtaining an occupational history.

PMID- 24113482
TI  - Facial palsy complicated by masked otomastoiditis in a 3-month-old infant.
AB  - BACKGROUND: The most common cause of facial palsy is idiopathic or Bell's palsy.
      Although uncommon in the postantibiotic era, otomastoiditis should receive more
      attention as a cause of facial palsy, especially in young children. Delay of
      identification and treatment may result in permanent neurological sequelae.
      OBJECTIVES: To describe a 3-month-old infant eventually diagnosed with masked
      otomastoiditis with initial presentation of facial palsy. CASE REPORT: We report
      a case of facial palsy complicated by masked otomastoiditis in a 3-month-old male
      infant. The facial palsy completely recovered after parenteral antibiotics and
      myringotomy. CONCLUSION: We use this case to emphasize that otomastoiditis should
      be considered in the differential diagnosis of young children with facial palsy.
      Diagnosis may be difficult as signs and symptoms of otitis media in young
      children are often nonspecific and subtle, particularly in infants. Early
      diagnosis and careful investigation of middle ear regions should be performed to
      avoid permanent sequelae.

PMID- 24113483
TI  - Does the experience of the writer affect the evaluative components on the
      standardized letter of recommendation in emergency medicine?
AB  - BACKGROUND: The Standardized Letter of Recommendation (SLOR) was developed in an
      attempt to standardize the evaluation of applicants to an emergency medicine (EM)
      residency. OBJECTIVE: Our aim was to determine whether the Global Assessment
      Score (GAS) and Likelihood of Matching Assessment (LOMA) of the SLOR for
      applicants applying to an EM residency are affected by the experience of the
      letter writer. We describe the distribution of GAS and LOMA grades and compare
      the GAS and LOMA scores to length of time an applicant knew the letter writer and
      number of EM rotations. METHODS: We conducted a retrospective review of all SLORs
      written for all applicants applying to three EM residency programs for the 2012
      match. Median number of letters written the previous year were compared across
      the four GAS and LOMA scores using an equality of medians test and test for trend
      to see if higher scores on the GAS and LOMA were associated with less experienced
      letter writers. Distributions of the scores were determined and length of time a
      letter writer knew an applicant and number of EM rotations were compared with GAS
      and LOMA scores. RESULTS: There were 917 applicants representing 27.6% of the
      total applicant pool for the 2012 United States EM residency match and 1253 SLORs
      for GAS and 1246 for LOMA were analyzed. The highest scores on the GAS and LOMA
      were associated with the lowest median number of letters written the previous
      year (equality of medians test across groups, p < 0.001; test for trend, p <
      0.001). Less than 3% received the lowest score for GAS and LOMA. Among letter
      writers that knew an applicant for more than 1 year, 45.3% gave a GAS score of
      "Outstanding" and 53.4% gave a LOMA of "Very Competitive" compared with 31.7% and
      39.6%, respectively, if the letter writer knew them 1 year or less (p = 0.002; p
      = 0.005). Number of EM rotations was not associated with GAS and LOMA scores.
      CONCLUSIONS: SLORs written by less experienced letter writers were more likely to
      have a GAS of "Outstanding" (p < 0.001) and a LOMA of "Very Competitive" (p <
      0.001) than more experienced letter writers. The overall distribution of GAS and
      LOMA was heavily weighted to the highest scores. The length of time a letter
      writer knew an applicant was significantly associated with GAS and LOMA scores.

PMID- 24113484
TI  - Traumatic diaphragmatic hernia.

PMID- 24113485
TI  - Bilateral perilunate dislocation after a fall.

PMID- 24113486
TI  - Questions on the role of the EPR effect in tumor targeting.

PMID- 24113487
TI  - In vivo real-time monitoring system of electroporation mediated control of
      transdermal and topical drug delivery.
AB  - Electroporation (EP) is a physical method for the delivery of molecules into
      cells and tissues, including the skin. In this study, in order to control the
      degree of transdermal and topical drug delivery, EP at different amplitudes of
      electric pulses was evaluated. A new in vivo real-time monitoring system based on
      fluorescently labeled molecules was developed, for the quantification of
      transdermal and topical drug delivery. EP of the mouse skin was performed with
      new non-invasive multi-array electrodes, delivering different amplitudes of
      electric pulses ranging from 70 to 570 V, between the electrode pin pairs.
      Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD),
      doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after
      EP. The new monitoring system was developed based on the delivery of FD to and
      through the skin. FD relative quantity was determined with fluorescence
      microscopy imaging, in the treated region of the skin for topical delivery and in
      a segment of the mouse tail for transdermal delivery. The application of electric
      pulses for FD delivery resulted in enhanced transdermal delivery. Depending on
      the amplitude of electric pulses, it increased up to the amplitude of 360 V, and
      decreased at higher amplitudes (460 and 570 V). Topical delivery steadily
      enhanced with increasing the amplitude of the delivered electric pulses, being
      even higher than after tape stripping used as a positive control. The non
      invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug,
      qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V
      pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360
      and 570 V pulse amplitudes verified the observed effects as obtained with FD and
      DOX, by the measured physiological responses of the mice as well as FEN plasma
      concentration. This study demonstrates that with the newly developed non-invasive
      multi-array electrodes and with the varying electric pulse amplitude, the amount
      of topical and transdermal drug delivery to the skin can be controlled.
      Furthermore, the newly developed monitoring system provides a tool for rapid real
      time determination of both, transdermal and topical delivery, when the delivered
      molecule is fluorescent.

PMID- 24113488
TI  - Innovation in healthcare. The challenge for laboratory medicine.
AB  - The delivery of healthcare is the product of a complex organization and it is not
      entirely surprising that innovation is not always considered to deliver on the
      expectations generated by invention. As policymakers and payers seek to improve
      the quality and value-for-money of healthcare, more attention is being directed
      at the barriers to innovation, and the challenges of translating inventions into
      outcomes. Laboratory medicine is one facet of healthcare that has generated
      considerable levels of invention but, while showing increasing volumes of
      activity over the past decades, it has not been recognized for generating the
      benefit in outcomes that might have been expected. One of the major reasons for
      this position has been the poor quality of evidence available to demonstrate the
      impact of laboratory investigations on health outcomes. Consequently an absence
      of evidence stifles the opportunity to develop the business case that
      demonstrates the link between test result and improved outcome. This has a major
      influence on the success of innovation in laboratory medicine. This review
      explores the process of innovation applied to laboratory medicine and offers an
      insight into how the impact of laboratory medicine on health outcomes can be
      improved. 

PMID- 24113491
TI  - Statistical mechanics of ribbons under bending and twisting torques.
AB  - We present an analytical study of ribbons subjected to an external torque. We
      first describe the elastic response of a ribbon within a purely mechanical
      framework. We then study the role of thermal fluctuations in modifying its
      elastic response. We predict the moment-angle relation of bent and twisted
      ribbons. Such a study is expected to shed light on the role of twist in DNA
      looping and on bending elasticity of twisted graphene ribbons. Our quantitative
      predictions can be tested against future single molecule experiments. 

PMID- 24113490
TI  - Molecular properties and fibril ultrastructure of types II and XI collagens in
      cartilage of mice expressing exclusively the alpha1(IIA) collagen isoform.
AB  - Until now, no biological tools have been available to determine if a cross-linked
      collagen fibrillar network derived entirely from type IIA procollagen isoforms,
      can form in the extracellular matrix (ECM) of cartilage. Recently, homozygous
      knock-in transgenic mice (Col2a1(+ex2), ki/ki) were generated that exclusively
      express the IIA procollagen isoform during post-natal development while type IIB
      procollagen, normally present in the ECM of wild type mice, is absent. The
      difference between these Col2a1 isoforms is the inclusion (IIA) or exclusion
      (IIB) of exon 2 that is alternatively spliced in a developmentally regulated
      manner. Specifically, chondroprogenitor cells synthesize predominantly IIA mRNA
      isoforms while differentiated chondrocytes produce mainly IIB mRNA isoforms.
      Recent characterization of the Col2a1(+ex2) mice has surprisingly shown that
      disruption of alternative splicing does not affect overt cartilage formation. In
      the present study, biochemical analyses showed that type IIA collagen extracted
      from ki/ki mouse rib cartilage can form homopolymers that are stabilized
      predominantly by hydroxylysyl pyridinoline (HP) cross-links at levels that
      differed from wild type rib cartilage. The findings indicate that mature type II
      collagen derived exclusively from type IIA procollagen molecules can form hetero
      fibrils with type XI collagen and contribute to cartilage structure and function.
      Heteropolymers with type XI collagen also formed. Electron microscopy revealed
      mainly thin type IIA collagen fibrils in ki/ki mouse rib cartilage.
      Immunoprecipitation and mass spectrometry of purified type XI collagen revealed a
      heterotrimeric molecular composition of alpha1(XI)alpha2(XI)alpha1(IIA) chains
      where the alpha1(IIA) chain is the IIA form of the alpha3(XI) chain. Since the N
      propeptide of type XI collagen regulates type II collagen fibril diameter in
      cartilage, the retention of the exon 2-encoded IIA globular domain would
      structurally alter the N-propeptide of type XI collagen. This structural change
      may subsequently affect the regulatory function of type XI collagen resulting in
      the collagen fibril and cross-linking differences observed in this study. 

PMID- 24113492
TI  - Clinical venous thromboembolism following joint surgery: effect of extended
      thromboprophylaxis on its annual frequency and postoperative pattern over 22
      years.
AB  - We describe annual incidences and 6-month postoperative patterns of clinical
      venous thromboembolism (VTE) in 9078 patients undergoing major joint surgery in a
      Scandinavian hospital. In cohort I (1989-1999), low-molecular-weight heparin
      thromboprophylaxis for 7 to 10 days was uniformly introduced, 5-week
      thromboprophylaxis becoming routine after total hip replacement (THR), partially
      applied after hip fracture surgery (HFS), but not used after total knee
      replacement (TKR) thereafter (2003-2011; cohort II). Mean annual VTE incidence
      was lower in cohort II than in cohort I after THR and HFS but not after TKR. In
      cohort I, the cumulative VTE incidence increased sharply during the first 5
      postoperative weeks in all groups, subsequently plateauing up to 6 months
      postsurgery. In cohort II, this incidence remained low and stable during 5 weeks
      post-THR, rising gradually up to 6 months, with a comparable but less pronounced
      pattern following HFS but not TKR. In conclusion, the VTE risk after major joint
      surgery seems to persist after 5- and 1-week prophylaxis in patients undergoing
      hip surgery and TKR, respectively. 

PMID- 24113493
TI  - Evaluation of the Practice Pattern of Medical Patients' VTE Prophylaxis With a
      Standard Risk Assessment Model Form: MERAM Study.
AB  - Hospitalized acutely ill patients face high risk for venous thromboembolism (VTE)
      unless appropriate thromboprophylaxis is applied. This study aimed to determine
      VTE prophylaxis practices for inpatients in Turkey and to evaluate the impact of
      physicians' training via a modified "Standard Medical Patients' VTE Risk
      Assessment Model (MERAM)." A total of 607 inpatients included in this national
      multicenter noninterventional observational registry were evaluated in terms of
      demographics, VTE risk, and preventive measures at 2 consecutive cross-sectional
      visits. Physicians were asked to complete a questionnaire on current VTE method
      risk assessment and other models including MERAM. The VTE prophylaxis rates
      significantly increased from 49.4% to 62.4% between visits (P < .05). The lack of
      risk evaluation decreased from 74.6% to 19.5% (P < .001). Percentage of
      physicians using prophylaxis and use of MERAM increased between visits. Physician
      training proved effective for providing general "awareness" of VTE prophylaxis
      and led to higher rates of risk assessment model-based appropriate VTE
      prophylaxis. 

PMID- 24113495
TI  - Family and relationship influences on parenting behaviors of young parents.
AB  - PURPOSE: Assess the influence of relationship and family factors during pregnancy
      on parenting behavior 6 months postpartum among low-income young parents.
      METHODS: Some 434 young expectant couples were recruited from obstetrics clinics
      during pregnancy and followed 6 months postpartum. Using a series of general
      estimating equations to control for the correlated nature of the data, we
      assessed the influence of relationship factors (e.g., relationship satisfaction,
      attachment) and family factors (e.g., family functioning, family history) during
      pregnancy on parenting (e.g., parenting involvement, time spent caregiving,
      parenting experiences, and parenting sense of competence) 6 months postpartum
      controlling for covariates. RESULTS: Relationship functioning related to
      parenting involvement, caregiving, parenting experiences, and parenting sense of
      competence. In addition, several family factors related to parenting. Mother
      involvement during childhood was related to more parenting involvement, parenting
      positive experiences, and parenting sense of competence. History of being spanked
      as a child related to less time spent caregiving and less positive life change
      from being a parent. Further, gender significantly moderated the associations
      between relationship and family factors and parenting behavior. Male parenting
      behavior was more influenced by relationship and family factors than female
      parenting. CONCLUSIONS: This study suggests the importance of relationship and
      family contexts for parenting behaviors of young mothers and fathers,
      highlighting the potential utility of involving both young mothers and fathers in
      parenting programs, and developing interventions that focus on strengthening
      young parents' romantic relationships and that address negative parenting
      experienced during childhood.

PMID- 24113496
TI  - Laser Doppler flux measurement for the assessment of cutaneous microcirculatio-
      critical remarks.
AB  - Back scattered Laser Doppler (LD) signals are composed of two different
      individual signals. The number of the moving particles and the speed of the
      particles in the measured tissue volume determine the frequency shift and the
      band width of the Doppler signal. The dependence of the Laser Doppler flux on the
      number of scattering particles is highly nonlinear: at very low hematocrit and
      high speed the axial migration of the cells to the centre of the blood vessels is
      very strong, so that in these cases - because of the parabolic flow profile - the
      Doppler flux measurement overestimates the mean real blood flow (up to two- or
      three-fold). The opposite is the case when the hematocrit is very high, then the
      blood flow might be underestimated (due to the increased amounts of blood cells
      near the vessel wall). In addition, a very change in number of moving particles -
      as can occur during the postprandial phase or during therapy - can change the
      signal also at a constant cell number. Also, it must be mentioned that the LD
      signal possibly is not only reflected by moving blood cells in the different skin
      layers but also by blood cells flowing in tissues below the skin (particularly
      below atrophied skin areas of older patients) so that in such cases the LD Flux
      signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest
      may still be within the normal range even in advanced states of disease, since
      the scattered light is sampled from a tissue volume which may contain also non
      nutritive shunt vessels. This critical analysis of the LD signals of course shall
      not lead to an overall rejection of the application of laser Doppler systems.
      Actual progress only can, however, be obtained under the exact consideration of
      anatomical conditions, technical restrictions and when generalizations are
      avoided. 

PMID- 24113497
TI  - Preoperative diagnosis of thyroid adenomas using high resolution contrast
      enhanced ultrasound (CEUS).
AB  - To evaluate the impact of high-resolution contrast-enhanced ultrasound (CEUS),
      Color Coded and Power Doppler Sonography (CCDS/PD), in the preoperative
      recognition of thyroid adenomas. A total of 64 patients (36 female, median age 54
      years) underwent surgery for thyroid adenoma. CEUS with linear multifrequency
      probes (6-9 or 6-15 MHz) and CCDS/PD was performed in all patients preoperatively
      by an experienced examiner and images were stored in PACS. Reading of the
      ultrasound images was performed in consensus by two experienced radiologists.
      Histopathology was achieved as standard of reference in all patients. Median
      diameter of the tumor lesions was 27 mm. 31 nodules were found on the left side.
      In B-Scan mode 13 (20%) adenomas showed complex cystic echo pattern and 44 (69%)
      had a complete and sharp hypoechoic edge. 43 (67%) thyroid adenomas had strong
      hypervascularization in CCDS/PD. In 61 (95%) adenomas early contrast enhancement
      was present in CEUS and 50 (78%) adenomas proved no wash-out or central wash-out
      with persisting edge enhancement. In 47 (73%) cases early contrast enhancement
      was combined with no washout or with central wash-out with persisting edge
      enhancement. 45 (70%) thyroid lesions had preoperatively been classified as
      benign lesions correctly. Dynamic evaluation of microcirculation by CEUS and
      CCDS/PD enables a more reliable preoperative characterization of thyroid
      adenomas. 

PMID- 24113498
TI  - Aggregated time intensity curves after transarterial chemoembolization with
      degradable starch microspheres: a feasibility study.
AB  - PURPOSE: To evaluate tumor perfusion by means of dynamic contrast-enhanced
      ultrasonography (DCEUS) and aggregated time intensity curves (TICs) after
      transarterial chemoembolization with degradable starch microspheres (DSM-TACE).
      MATERIAL AND METHODS: 18 patients underwent 36 DCEUS examinations conducted via
      contrast agent application before and after DSM-TACE. Based on time intensity
      curves (TICs), we analyzed the microcirculation of the embolized HCC lesions with
      a dedicated perfusion software. RESULTS: Signal intensity was significantly
      reduced (p <= 0.001) after DSM-TACE at all time points measured. The mean signal
      intensity after 5, 10, 15, 20 and 25 s was 375.18 +/- 16.41, 455.66 +/- 17.92,
      294.47 +/- 19.91, 246.51 +/- 20.99 and 173.45 +/- 25.80 before TACE and 49.47 +/-
      2.43, 49.51 +/- 2.40, 37.40 +/- 2.45, 27.48 +/- 2.65 and 27.96 +/- 3.01 after
      TACE. CONCLUSION: In this study, tumor perfusion could be accurately evaluated by
      means of DCEUS and aggregated TICs after DSM-TACE.

PMID- 24113499
TI  - Rheological parameters in the umbilical cord blood in moderate and severe forms
      of preeclampsia.
AB  - INTRODUCTION: Previous studies have dealt with maternal blood rheology in
      preeclampsia (PE), but only a few focused on the fetal rheological parameters in
      this maternal state. PE is one of the most common severe complications of
      pregnancy world-wide associated with high maternal morbidity and mortality and
      intrauterine fetal growth restriction. Our objective was to explore the
      rheological parameters in the umbilical cord blood at term in the presence of
      moderate and severe forms of PE. METHODS: A subgroup analysis was performed in a
      community based retrospective study of 4,951 consecutively recorded singleton
      pregnant women of whom 423 had PE. In the latter, umbilical cord blood was
      collected during delivery for testing of hematological and blood rheological
      parameters of their fetus. Fetal results from uneventful pregnancy were compared
      with those associated with preeclampsia. Furthermore, results were also evaluated
      in the presence of moderate and severe forms of PE. Plasma viscosity (pv) was
      examined using KSPV 1 Fresenius and Red Blood Cell (RBC) aggregation (stasis: E0
      and low shear: E1) using MA1-Aggregometer; Myrenne. RESULTS: According to the
      definition of the German Society of Gynecology and Obstetrics (DGGG) 314 women
      had moderate (74.2%), while 109 had severe forms of PE due to the presence of a
      blood pressure > 170/110 mmHg (n = 41; 9.7%), and/or IUGR < 5th percentile (n =
      28; 6.6%), and/or HELLP-Syndrome (n = 10; 2.4%), and/or proteinuria >= 5 g/24 h
      (n = 30; 7.1%). When comparing the fetal results from pregnancies with and
      without preeclampsia mean hemoglobin values (p < 0.001) and hematocrit (p <
      0.001) were markedly higher, while plasma viscosity (p = 0.006) and erythrocyte
      aggreagtion (stase: p = 0.35; low shear: p = 0.08) were lower in association with
      preeclampsia. Gestational age, fetal birth-weight and umbilical arterial cord
      blood pH in women with severe PE was statistically significant lower as compared
      to those with moderate disease (p < 0.001). Mean hemoglobin level and hematocrit
      were higher in fetus from women with severe compared to moderate PE, while plasma
      viscosity (1.03 +/- 0.07 mPas vs. 1.05 +/- 0.07; p = 0.05) and erythrocyte
      aggregation in stase (2.3 +/- 2.47 vs. 2.41 +/- 2.46; p = 0.11) as well as under
      low shear (7.86 +/- 4.63 vs. 8.06 +/- 4.60; p = 0.15) were lower. HELLP-Syndrome
      was associated with the lowest plasma viscosity (1.00 +/- 0.07 mPas; p = 0.019)
      and erythrocyte aggregation (low shear: 5.1 +/- 5.0; p = 0.04) in fetus.
      CONCLUSION: The results of this study including a notable number of patients with
      PE and their newborns revealed an in part statistically significant association
      between variables of blood rheology and the presence, severity and type of
      preeclampsia with a trend towards hyperviscosity in severe forms of preeclampsia.
      The behaviour of blood rheological components in the neonate is remarkable since
      the number of red blood cells is raised while RBC aggregability and plasma
      viscosity is low.

PMID- 24113500
TI  - Viscosity of radiographic contrast media.
AB  - The data on the viscosities of radiographic contrast media (RCM) in the
      literature diverge, sometimes considerably. A direct comparative study of RCM
      appears reasonable and necessary, since different studies have been based on the
      assumption of the correctness of historical data from the literature. RCM
      viscosities in the literature differ for one and the same contrast medium by up
      to 19.1%. Therefore, the measurement of these substances was carried out in terms
      of their viscosity with the same device under identical experimental conditions
      at virtually the same time. Of the 15 investigated RCMs, the viscosities were in
      9 cases higher than the highest specification in the literature, the values were
      in the range of literature in three substances, and in three cases the values
      were a little below the lowest values in literature. 

PMID- 24113501
TI  - Influence of iodine-containing radiographic contrast media on the phenotype of
      erythrocytes from different laboratory animal species.
AB  - It is well known that clinically relevant concentrations of iodine-containing
      radiographic contrast media (CM) induce morphological changes in human
      erythrocytes. However, there are only few reports about CM effects on
      erythrocytes of animals (e.g. mice, rats, rabbits, and pigs). Thus, two
      conventional iodine-containing CM (iodixanol, VisipaqueTM 320; iomeprol,
      IomeprolTM 350) were tested for their effects on the morphology of erythrocytes
      from these. After venous blood sampling and blood centrifugation, the autologous
      plasma was supplemented with 40 vol% CM. Then, a defined number of erythrocytes
      was incubated in this CM-supplemented plasma for 5 min at body temperature (37
      degrees C). Subsequently, 10 MUL of the cell suspension were transferred to a
      purified glass slide and the number of discocytes, echinocytes, and acanthocytes
      was counted within a total number of 100 erythrocytes (40 fold primary
      magnification, transmitted light mode). Shape changes of the erythrocytes from
      all animal species strongly depended on the type of CM and compared to the
      effects which have already been described for human erythrocytes. Incubation in
      both CM resulted in morphological changes of the erythrocytes. Incubation in a
      iodixanol/plasma mixture induced the lowest echinocyte or acanthocyte formation.
      Porcine erythrocytes showed a much more distinct shape change than those of other
      animal species and humans. These results suggest erythrocytes from mice, rats,
      and rabbits are a suitable model system for a model system for human erythrocytes
      when CM effects on the cellular shape of erythrocytes have to be tested. The
      distinct deformation of the pig erythrocytes could be due to differences in the
      pig erythrocyte membrane or the physical and chemical constitution of pig
      erythrocytes. 

PMID- 24113502
TI  - Influence of a silicon (Si14)-based coating substrate for biomaterials on
      fibroblast growth and human C5a.
AB  - Despite considerable efforts in biomaterial development there is still a lack on
      substrates for cardiovascular tissue engineering approaches which allow the
      establishment of a tight a functional endothelial layer on their surface to
      provide hemocompatibility. The study aimed to test the biocompatibility of a
      silicon (Si14)-based coating substrate (Supershine Medicare, Permanon) which was
      designed to resist temperatures from -40 degrees C up to 300 degrees C and which
      allows the use of established heat-inducing sterilization techniques
      respectively. By X-ray photoelectron spectroscopy it could be validated that this
      substrate is able to establish a 40-50 nm thick layer of silica, oxygen and
      carbon without including any further elements from the substrate on an exemplary
      selection of materials (silicone, soda-lime-silica glass, stainless steel).
      Analysis of the LDH-release, the cell activity/proliferation (MTS assay) and the
      cell phenotype after growing 3T3 cells with extracts of the coated materials did
      not indicate any signs of cytotoxicity. Additionally by measuring the C5a release
      after exposure of the coated materials with human serum it could be demonstrated,
      that the coating had no impact on the activation of the complement system. These
      results generally suggest the tested substrate as a promising candidate for the
      coating of materials which are aimed to be used in cardiovascular tissue
      engineering approaches. 

PMID- 24113503
TI  - Heparinized blood better preserves cellular energy charge and vascular functions
      of intraoperatively stored saphenous vein grafts in comparison to isotonic sodium
      chloride-solution.
AB  - OBJECTIVE: Several studies have addressed the optimal storage conditions for
      vascular grafts during surgery. The results remain contradictionary. This may be
      attributed to the fact, that the various vascular beds have a different
      sensitivity to storage. We analyzed the impact of storage in isotonic saline
      solution (NaCl) or heparinized blood the vascular functions of human saphenous
      vein grafts. Special care was taken to choose storage conditions which are
      relevant for intraoperative storage of a saphenous vein graft in a setting of
      coronary artery bypass grafting with vein and internal mammary artery as grafts.
      METHODS: Intraoperatively isolated V. saphena-segments (n = 36) were stored in
      NaCl or heparinized blood for approximately 30 minutes at room temperature.
      Subsequently, the segments were examined in a Mulvany-myograph. Following
      preconstriction with norepinephrine, concentration-relaxation curves were
      assessed for bradykinin and sodium-nitroprusside to assess developed vessel-wall
      tension as well as endothelium- and smooth-muscle-cell dependent vasorelaxation.
      The availability of adenosintriphosphate (energy charge) was determined based on
      liquid chromatography measurements of nucleotide tissue levels. RESULTS: Mean
      storage time was 27.4 +/- 2.4 min in NaCl- and 26.3 +/- 2.7 min in blood-group,
      respectively. After this period, receptor-dependent and-independent maximum of
      developed vessel wall tension was significantly reduced in NaCl-group (p = 0.05
      and p = 0.045, respectively). Furthermore, the energy charge was significantly (p
      = 0.046) better preserved after blood storage (74 +/- 1%) in comparison to NaCl
      group (68 +/- 2%). Endothelium-induced vasodilatation in response to bradykinin
      reached only 12.3 +/- 2.5% in NaCl-group, but 19.3 +/- 5.2% in blood-group (p =
      0.033). Alike, EC50-concentration of bradykinin for half-maximal relaxation was
      significantly lower in blood- than in NaCl-group (log EC50 -7.08 +/- 0.3 and 
      5.91 +/- 0.4; respectively; p = 0.046). Endothelium-independent smooth muscle
      relaxation in response to sodium-nitroprusside was not different between both
      groups. CONCLUSION: Heparinized blood better preserves vascular contractile and
      endothelial functions of the saphenous vein graft. Storage in NaCl rapidly
      compromises vascular functions and impaires cellular energy. NaCl should no
      longer be recommended for intraoperative storage of harvested V. saphena grafts.

PMID- 24113504
TI  - Prospective clinical trial on dosage optimizing of tranexamic acid in non
      emergency cardiac surgery procedures.
AB  - After withdrawal of aprotinin in 2008 only tranexamic acid (TxA, Cyclocapron,
      Pfitzer, Germany) remains available as antihyperfibrinolytic agent in Europe.
      Dosage (from 1 g to 20 g) and application strategy (single shot i.v., infusion
      i.v., topical) reflect an indiscriminate use of TXA in cardiac surgery. We use
      data analysis of three registries to evaluate safety issues and sufficiency of
      different TxA dosages in our center. METHODS: Registry 1: Single shot ultra-low
      dose TxA (1 g in priming volume). Registry 2: Single shot medium dose TxA (5 g in
      priming volume). Registry 3: Single shot medium dose TxA (3 g in priming volume)
      and continuous, weight-adapted administration during cross clamping. Independence
      of surgeon's preference was achieved by changing dosage every surgery day
      regardless of operation schedule. RESULTS: Data analysis was carried out on 1182
      consecutive, elective patients (1 g TxA n = 415; 3 g + x g TA n = 367; mean TxA
      dose 4.4 g +/- 1.0 g; 5 g TxA n = 400). Patient characteristics were well matched
      in all three registries (mean age: 69 +/- 9.5y, BMI 28.2 +/- 4.7, Creatinin 107.5
      +/- 52.8 MUM), as were performed surgical procedures (excluding organ
      transplantation). Postoperative data showed no significant differences for blood
      loss and major adverse events (1 g vs. 3 + g vs. 5 g: blood loss: 894 +/- 1479
      vs. 903 +/- 1282 vs. 1004 +/- 1604 ml; stroke: 1.5 vs. 1.6 vs. 1.5%; myocardial
      infarction 2.7 vs. 3.3 vs. 1.3%; 30d mortality 3.9 vs. 4.2 vs. 4.8%,
      respectively). Secondary endpoints (de novo dialysis, transfusion requirement,
      ICU and total treatment time) showed no significant differences between
      registries. CONCLUSION: Use of 1 g TxA is safe and sufficient for elective
      patients with on pump cardiac surgery and thus has been established as strategy
      of choice in our center.

PMID- 24113505
TI  - Distribution of actin of the human erythrocyte membrane cytoskeleton after
      interaction with radiographic contrast media.
AB  - A type-dependent chemotoxic effect of radiographic contrast media on erythrocytes
      and endothelial cells was reported several times. While mechanisms of toxicity
      are still unclear the cellular reactions e.g. echinocyte formation in
      erythrocytes and the buckling of endothelial cells coincided with deterioration
      of capillary perfusion (in patients with coronary artery disease) and tissue
      oxygen tension (in the myocardium of pigs). Whether the shape changes in
      erythrocytes coincide with changes in the arrangement of actin, the core of the
      actin-spectrin cytoskeletal network and possible actor in membrane stresses and
      deformation is not known until now. To get specific informations actin was
      stained using two different staining methods (antibodies to beta-actin staining
      oligomeric G-actin and polymeric F-actin and Phalloidin-Rhodamin staining
      polymeric F-actin only). In addition, an advanced version of confocal laser
      scanning microscopes was used enabling the display of the actin arrangement near
      substrate surfaces. Blood smears were produced after erythrocyte suspension in
      autologous plasma or in two different plasma/RCM mixtures. In this study an even
      homogenous distribution of fine grained globular actin in the normal human
      erythrocyte could be demonstrated. After suspension of erythrocytes in a
      plasma/Iodixanol mixture an increased number of membrane protrusions appeared
      densely filled with intensely stained actin similar to cells suspended in
      autologous plasma, however, there in less numbers. Suspension in Iopromide, in
      contrast, induced a complete reorganization of the cytoskeletal actin: the fine
      grained globular actin distribution disappeared and only few, long and thick
      actin filaments bundled and possibly polymerized appeared, instead, shown here
      for the first time. 

PMID- 24113506
TI  - Influence of fibre diameter and orientation of electrospun
      copolyetheresterurethanes on smooth muscle and endothelial cell behaviour.
AB  - Polymers exhibiting cell-selective effects represent an extensive research field
      with high relevance for biomedical applications e.g. in the cardiovascular field
      supporting re-endothelialization while suppressing smooth muscle cell overgrowth.
      Such an endothelial cell-selective effect could be recently demonstrated for a
      copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and
      poly(epsilon-caprolactone) segments, which selectively enhanced the adhesion of
      human umbilical vein endothelial cells (HUVEC) while suppressing the attachment
      of smooth muscle cells (SMC). In this study we investigated the influence of the
      fibre orientation (random and aligned) and fibre diameter (2 MUm and 500 nm) of
      electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC
      and SMC. Adhesion, viability and proliferation of HUVEC was diminished when the
      fibre diameter was reduced to a submicron scale, while the orientation of the
      microfibres did only slightly influence the cellular behaviour. In contrast, a
      submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds
      with micron-sized single fibres could be promising candidate materials for cell
      selective stent coatings. 

PMID- 24113507
TI  - Leukocyte-endothelial interactions within the ocular microcirculation in
      inflammation and infection.
AB  - Leukocyte-endothelial interactions within the microvasculature represent a
      hallmark of inflammation regardless of whether the inflammation results from non
      infectious or infectious triggers. In this review, we highlight features of
      leukocyte recruitment in ocular disease and postulate mechanisms by which the
      infiltrating cells may lead to the progression of the ocular inflammatory
      response, including cytokine and chemokine production, T cell or non-T cell
      responses. Additionally, ex-vivo and in vivo methods used to study the general
      features of the immune response are discussed, with a specific focus on
      intravital imaging, which allows real-time non-invasive examination of leukocyte
      endothelial interactions in the ocular microvasculature. At the present time
      there are still significant gaps in our understanding of the process of leukocyte
      recruitment in vivo in different microvascular beds. Further studies using non
      invasive imaging approaches, such as intravital microscopy, provide an
      opportunity to study dynamic tissue-specific leukocyte-endothelial interactions
      in vivo and identify novel targets for early intervention in the inflammatory
      process. This knowledge is essential to the rational use of therapeutics to
      resolve inflammation in ocular disease. 

PMID- 24113508
TI  - Case-oriented self-learning and review in pharmacology teaching.
AB  - BACKGROUND: To cultivate students' ability to use the pharmacology principles in
      medical practice, case-oriented self-learning and review has partly replaced
      lecture-based teaching in our pharmacology course. The aim of this study is to
      investigate the effects of an innovative teaching model in pharmacology teaching
      on the performance of medical undergraduates. METHODS: A total of 185 third-year
      medical students participated in the study in 2011 and 2012. The students were
      randomized into the study group (case-oriented self-learning and review) and
      control group (traditional lecture-based teaching). Examination performances
      between the students in the 2 groups were compared, and questionnaires were
      designed for both the students participating in the study group and the teachers
      to assess the new teaching method. RESULTS: Mid-term examination performances in
      2011 and 2012 were significantly better for the students in the study group than
      those in the control group (P<0.01). On the final examination in 2011,
      significantly more students received an assessment of "excellent" in the study
      group than in the control group (P<0.05). Moreover, students in the study group
      performed better than those in the control group on the final examination in
      2012. The data from the questionnaires indicated that both teachers and students
      in the study group generally held positive attitudes toward the innovative
      teaching model. CONCLUSIONS: Case-oriented self-learning and review can improve
      students' internalization of basic pharmacological principles and provide a
      greater opportunity for self-study and collaborative study. The examination
      composition can affect the efficacy of the assessment of problem solving
      abilities.

PMID- 24113510
TI  - Importance of dispersion forces for prediction of thermodynamic and transport
      properties of some common ionic liquids.
AB  - An extensive study of interaction energies in ion pairs of pyrrolidinium and
      imidazolium ionic liquids is presented. The Cnmpyr and Cnmim cations with varying
      alkyl chains from Methyl, Ethyl, n-Propyl to n-Butyl were combined with a wide
      range of routinely used IL anions such as chloride, bromide, mesylate (CH3SO3 or
      Mes), tosylate (CH3PhSO3 or Tos), bis(trifluoromethanesulfonyl)amide (NTf2),
      dicyanamide (N(CN)2 or dca), tetrafluoroborate (BF4) and hexafluorophosphate
      (PF6). A number of energetically favourable conformations were studied for each
      cation-anion combination. The interaction energy and its dispersion component of
      the single ion pairs were calculated using a sophisticated state-of-the-art
      approach: a second-order of Symmetry Adapted Perturbation Theory (SAPT). A
      comparison of energetics depending on the cation-anion type, as well as the mode
      of interaction was performed. Dispersion forces were confirmed to be of
      importance for the overall stabilisation of ionic liquids contributing from 28 kJ
      mol(-1) in pyrrolidinium ion pairs to 59 kJ mol(-1) in imidazolium ion pairs. The
      previously proposed ratio of total interaction energy to dispersion components
      and melting points was assessed for this set of ionic liquids and was found to
      correlate with their melting points for the anionic series, producing separate
      trends for the Cnmim and Cmpyr series of cations. Chlorides, bromides and
      tetrafluoroborates formed close-to-ideal correlations when both types of cations,
      Cnmim and Cnmpyr, were combined in the same trend. Correlation of the dispersion
      component of the interaction energy with transport properties such as
      conductivity and viscosity was also considered. For imidazolium-based ionic
      liquids strong linear correlations were obtained, whereas pyrrolidinium ionic
      liquids appeared to be insensitive to this correlation. 

PMID- 24113509
TI  - Microfluidic-based patterning of embryonic stem cells for in vitro development
      studies.
AB  - In vitro recapitulation of mammalian embryogenesis and examination of the
      emerging behaviours of embryonic structures require both the means to engineer
      complexity and accurately assess phenotypes of multicellular aggregates. Current
      approaches to study multicellular populations in 3D configurations are limited by
      the inability to create complex (i.e. spatially heterogeneous) environments in a
      reproducible manner with high fidelity thus impeding the ability to engineer
      microenvironments and combinations of cells with similar complexity to that found
      during morphogenic processes such as development, remodelling and wound healing.
      Here, we develop a multicellular embryoid body (EB) fusion technique as a higher
      throughput in vitro tool, compared to a manual assembly, to generate
      developmentally relevant embryonic patterns. We describe the physical principles
      of the EB fusion microfluidic device design; we demonstrate that >60 conjoined
      EBs can be generated overnight and emulate a development process analogous to
      mouse gastrulation during early embryogenesis. Using temporal delivery of bone
      morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day
      6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation
      in murine embryonic stem cells leading to expression of Brachyury-T-green
      fluorescent protein (T-GFP), an indicator of primitive streak development and
      mesoderm differentiation during gastrulation. The proposed microfluidic approach
      could be used to manipulate hundreds or more of individual embryonic cell
      aggregates in a rapid fashion, thereby allowing controlled differentiation
      patterns in fused multicellular assemblies to generate complex yet spatially
      controlled microenvironments. 

PMID- 24113511
TI  - Evaluation of Streptomyces strains isolated from herbal vermicompost for their
      plant growth-promotion traits in rice.
AB  - Six actinomycetes, CAI-13, CAI-85, CAI-93, CAI-140, CAI-155 and KAI-180, isolated
      from six different herbal vermi-composts were characterized for in vitro plant
      growth-promoting (PGP) properties and further evaluated in the field for PGP
      activity in rice. Of the six actinomycetes, CAI-13, CAI-85, CAI-93, CAI-140 and
      CAI-155 produced siderophores; CAI-13, CAI-93, CAI-155 and KAI-180 produced
      chitinase; CAI-13, CAI-140, CAI-155 and KAI-180 produced lipase; CAI-13, CAI-93,
      CAI-155 and KAI-180 produced protease; and CAI-13, CAI-85, CAI-140 and CAI-155
      produced beta-1-3-glucanase whereas all the six actinomycetes produced cellulase,
      hydrocyanic acid and indole acetic acid (IAA). The actinomycetes were able to
      grow in NaCl concentrations of up to 8%, at pH values between 7 and 11,
      temperatures between 20 and 40  degrees C and compatible with fungicide bavistin
      at field application levels. In the rice field, the actinomycetes significantly
      enhanced tiller numbers, panicle numbers, filled grain numbers and weight, stover
      yield, grain yield, total dry matter, root length, volume and dry weight over the
      un-inoculated control. In the rhizosphere, the actinomycetes also significantly
      enhanced total nitrogen, available phosphorous, % organic carbon, microbial
      biomass carbon and nitrogen and dehydrogenase activity over the un-inoculated
      control. Sequences of 16S rDNA gene of the actinomycetes matched with different
      Streptomyces species in BLAST analysis. Of the six actinomycetes, CAI-85 and CAI
      93 were found superior over other actinomycetes in terms of PGP properties, root
      development and crop productivity. qRT-PCR analysis on selected plant growth
      promoting genes of actinomycetes revealed the up-regulation of IAA genes only in
      CAI-85 and CAI-93.

PMID- 24113513
TI  - Lack of correlation between preoperative and intraoperative liver hemodynamics: a
      descriptive analysis.
AB  - BACKGROUND: Adult living-donor liver transplantation recipients undergo important
      hemodynamic changes during the procedure, which in turn have proven to be of the
      upmost importance when dealing with small grafts, to avoid the so-called "small
      for-size" syndrome. METHODS: Back in 2003, we started a hemodynamic monitoring
      protocol in adult living-donor liver transplantation recipients, which evaluated
      the hemodynamic status of the patient 24 hr before, during, and 3 days after
      transplantation. We analyzed the correlation between the same hemodynamic
      variables measured in the hemodynamic laboratory and those taken in the operating
      room. RESULTS: With the exception of cardiac index and indexed systemic vascular
      resistance, all the other hepatic and systemic hemodynamic parameters measured
      before and during the intervention, as well as during and after the intervention,
      showed a lack of correlation. CONCLUSION: The observed lack of correlation may
      happen due to many factors, such as the influence of vasoactive and anesthetic
      drugs, total muscular relaxation, or the presence of an open abdomen. As a
      result, a direct comparison between hemodynamic values should only be done when
      measured in the same conditions.

PMID- 24113512
TI  - Prognostic factors affecting survival at recurrence of hepatocellular carcinoma
      after living-donor liver transplantation: with special reference to
      neutrophil/lymphocyte ratio.
AB  - BACKGROUND: In living-donor liver transplantation (LDLT) for hepatocellular
      carcinoma (HCC), it is important to predict not only who may be susceptible to
      recurrence but also who may survive longer. The neutrophil/lymphocyte ratio (NLR)
      is useful to properly assess the patient without decreasing the long-term
      survival after LDLT. In this study, we investigated the relationship between NLR
      and prognosis of patients with recurrent HCC after LDLT. METHODS: In total, 167
      LDLTs for HCC were enrolled in this study. Clinicopathologic factors for HCC
      recurrence after LDLT were investigated and prognostic factors were examined with
      respect to survival. RESULTS: The following factors were found to be significant
      in patients with HCC recurrence compared with the controls: alpha-fetoprotein
      ?300 ng/mL, des-gamma-carboxyprothrombin ?300 mAU/mL, NLR ?4, tumor number >3,
      tumor size ?5 cm, duration of last treatment of HCC to LDLT <3 months, Milan
      criteria exceeded, histologic tumor number ?10, histologic tumor size >5 cm, poor
      differentiation, presence of histologic vascular invasion, adjuvant chemotherapy,
      and interferon therapy against patients with hepatitis C virus. Male sex,
      interferon therapy against patients with hepatitis C virus, alpha-fetoprotein
      ?300 ng/mL at recurrence, NLR ?4 at recurrence, and nonsurgical resection for
      recurrent HCC were significantly related to poor prognosis. The 3-year survival
      rate after recurrence was 0% in patients with NLR ?4 and 43.6% in patients with
      NLR <4. NLR was reelevated after LDLT in patients who later died; however, NLR
      gradually decreased in surviving patients. CONCLUSION: NLR at recurrence is a
      prognostic factor affecting survival after recurrence in LDLT for HCC.

PMID- 24113514
TI  - Functional status and survival after kidney transplantation.
AB  - BACKGROUND: Older patients constitute a growing proportion of U.S. kidney
      transplant recipients and often have a high burden of comorbidities. A summary
      measure of health such as functional status might enable transplant professionals
      to better evaluate and counsel these patients about their prognosis after
      transplant. METHODS: We linked United Network for Organ Sharing registry data
      about posttransplantation survival with pretransplantation functional status data
      (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among
      individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We
      examined the relationship between survival and functional status with
      multivariable Cox regression, adjusted for age. Using logistic regression models
      for 3-year survival, we also estimated the reduction in deaths in the
      hypothetical scenario that recipients with poor functional status in this cohort
      experienced modest improvements in function. RESULTS: The cohort comprised 10,875
      kidney transplant recipients with a mean age of 50 years; 14% were >=65.
      Differences in 3-year mortality between highest and lowest PF groups ranged from
      3% among recipients <35 years to 14% among recipients >=65 years. In
      multivariable Cox regression, worse PF was associated with higher mortality
      (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions
      between PF and age were nonsignificant. We estimated that 11% fewer deaths would
      occur if kidney transplant recipients with the lowest functional status
      experienced modest improvements in function. CONCLUSIONS: Across a wide age
      range, functional status was an independent predictor of posttransplantation
      survival. Functional status assessment may be a useful tool with which to counsel
      patients about posttransplantation outcomes.

PMID- 24113516
TI  - [The importance of adherence to oral therapies in the field of oncology: the
      example of breast cancer].
AB  - Today, over 40 different oral anticancer therapies are available in the French
      prescription pricing authority dictionary. Adherence to these therapies has
      become a major issue in the field of oncology. Most of the available research has
      focused on adherence to hormonal therapy for breast cancer (BC). The objective of
      this paper is to synthesize current knowledge on adherence and persistence to
      hormonal therapy for BC. Available studies display significant heterogeneity due
      to variability in the measurements and data sources used, as well as in the
      timing of the measurements. Adherence and persistence estimates have recently
      been summarized in a meta-regression analysis. For tamoxifen, adherence ranges
      from 79% at one year to 65% at five years, and for Aromatase Inhibitors (AI),
      from 80% at one year to 72% at five years. Persistence decreases with the
      increasing duration of treatment: from a high of 86% of patients persistent at 1
      year to a low of 53% at five years for tamoxifen, and from 88% to 69% for AI.
      Some of the modifiable determinants of adherence are directly linked to the
      patient-physician relation, to information provided during consultations, or to
      the specialty of the physician involved in the patient follow-up. Non-modifiable
      determinants, such as age or comorbidities, can be used to identify sub-groups of
      patients at high risk of non-adherence in order to target interventions. Few
      trials have been conducted in oncology to evaluate the efficacy of interventions
      to improve adherence. Adherence directly impacts both the efficacy of treatment
      and long-term treatment costs. Interventions to improve adherence to oral
      therapies should be systematically promoted in oncology. Improving adherence
      should be considered a priority in the field, lest physicians continue writing
      inefficient prescriptions for highly efficacious treatments. 

PMID- 24113515
TI  - The clinical potential of targeted nanomedicine: delivering to cancer stem-like
      cells.
AB  - Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment
      resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to
      eliminate CSCs is a desirable approach for developing a more effective anticancer
      therapy. We have developed a tumor-targeting nanodelivery platform (scL) for
      systemic administration of molecular medicines. Following treatment with the scL
      nanocomplex carrying various payloads, we have observed exquisite tumor-targeting
      specificity and significant antitumor response with long-term survival benefit in
      numerous animal models. We hypothesized that this observed efficacy might be
      attributed, at least in part, to elimination of CSCs. Here, we demonstrate the
      ability of scL to target both CSCs and differentiated nonstem cancer cells (non
      CSCs) in various mouse models including subcutaneous and intracranial xenografts,
      syngeneic, and chemically induced tumors. We also show that systemic
      administration of scL carrying the wtp53 gene was able to induce tumor growth
      inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal
      cancer xenografts suggesting that this could be an effective method to reduce
      cancer recurrence and treatment resistance. This scL nanocomplex is being
      evaluated in a number of clinical trials where it has been shown to be well
      tolerated with indications of anticancer activity. 

PMID- 24113518
TI  - Development of a behaviour change communication tool for medical students: the
      'Tent Pegs' booklet.
AB  - OBJECTIVE: To describe the development and validation of a behaviour change
      communication tool for medical students. METHODS: Behaviour change techniques
      (BCTs) were identified within the literature and used to inform a communication
      tool to support medical students in discussing health-related behaviour change
      with patients. BCTs were organized into an accessible format for medical students
      (the 'Tent Pegs' booklet) and validated using discriminant content validity
      methods with 11 expert judges. RESULTS: One-sample t-tests showed that judges
      reliably mapped BCTs onto six of the seven Tent Pegs domains (confidence rating
      means ranged from 4.0 to 5.1 out of 10, all p<=0.002). Only BCTs within the
      'empowering people to change' domain were not significantly different from the
      value zero (mean confidence rating=1.2, p>0.05); these BCTs were most frequently
      allocated to the 'addressing thoughts and emotions' domain instead. CONCLUSION:
      BCTs within the Tent Pegs booklet are reliably allocated to corresponding
      behaviour change domains with the exception of those within the 'empowering
      people to change' domain. PRACTICE IMPLICATIONS: The existing evidence-base on
      BCTs can be used to directly inform development of a communication tool to
      support medical students facilitate health behaviour change with patients.

PMID- 24113519
TI  - Response to Nasir et al.

PMID- 24113521
TI  - Physical objects as vehicles of cultural transmission: maintaining harmony and
      uniqueness through colored geometric patterns.
AB  - We examined how cultural values of harmony and uniqueness are represented and
      maintained through physical media (i.e., colorings of geometric patterns) and how
      individuals play an active role in selecting and maintaining such cultural
      values. We found that colorings produced by European American adults and children
      were judged as more unique, whereas colorings produced by Japanese adults and
      children were judged as more harmonious, reflecting cultural differences in
      values. Harmony undergirded Japanese participants' preferences for colorings,
      whereas uniqueness undergirded European American participants' preferences for
      colorings. These cultural differences led participants to prefer own-culture
      colorings over other-culture colorings. Moreover, bicultural participants'
      preferences acculturated according to their identification with their host
      culture. Furthermore, child rearers in Japan and Canada gave feedback about the
      children's colorings that were consistent with their culture's values. These
      findings suggest that simple geometric patterns can embody cultural values that
      are socialized and reinforced from an early age. 

PMID- 24113522
TI  - Suppression of voltage-gated Na(+) channels and neuronal excitability by
      imperatorin.
AB  - Imperatorin is a naturally occurring furocoumarin compound isolated from plants
      such as Angelica archangelica and Cnidium monnieri. It has multiple
      pharmacological effects including anticonvulsant effects. Here we determined the
      effects of imperatorin on voltage-gated Na(+) channels (VGSC) using whole-cell
      patch clamp techniques in differentiated neuronal NG108-15 cells. We showed that
      imperatorin inhibited VGSC; such inhibition did not show state-dependence.
      Imperatorin caused a left shift in the steady-state inactivation curve without
      affecting activation gating. The inhibition of VGSC by imperatorin displayed a
      mild frequency-dependence. Imperatorin was also shown to inhibit VGSC and action
      potential amplitude without affecting voltage-gated K(+) channels in rat
      hippocampal CA1 neurons. In conclusion, our results suggest that imperatorin
      dampens neuronal excitability by inhibiting VGSC. 

PMID- 24113523
TI  - Chlorbipram: a novel PDE4 inhibitor with improved safety as a potential
      antidepressant and cognitive enhancer.
AB  - Major depressive disorder is a common, but serious, psychiatric dysfunction that
      affects 21% of the population worldwide. Rolipram, a first-generation
      phosphodiesterase-4 (PDE4) inhibitor, has been shown to have significant
      antidepressant and cognitive enhancement effects; however, it was unsuccessful in
      clinic trials because of PDE4-dependent side effects such as nausea and emesis.
      In this study, we investigated the neuropharmacology of the novel PDE4 inhibitor
      chlorbipram and the classical PDE4 inhibitor rolipram. Using antidepressant
      sensitive behavioral tests, we demonstrated that the acute single administration
      of chlorbipram (0.075-0.6 mg/kg) produced antidepressant-like effects, as
      evidenced by decreases in the duration of immobility in Kunming mice in the
      forced swim and tail suspension tests, and no significant changes in locomotor
      activity. Scopolamine-induced cognitive dysfunction was also significantly
      attenuated in the Morris water maze test after the treatment of Sprague Dawley
      rats with different doses of chlorbipram (0.5-1.5mg/kg). Furthermore, we
      evaluated the emetic potential of chlorbipram in beagle dogs. After oral
      administration, 0.5mg/kg rolipram showed emetic profiles in all dogs within 20
      minutes, whereas chlorbipram did not induce any emesis during the 120-min
      observation period, even at the 1.0mg/kg dose. Together, our data suggest that
      chlorbipram is a novel antidepressant and cognitive enhancer with little or no
      emetic potency.

PMID- 24113524
TI  - Sirtuin 1 is upregulated in young obese Zucker rat cerebral arteries.
AB  - Many diseases, including metabolic syndrome, are characterised by endothelial
      dysfunction mediated by reduced nitric oxide bioavailability and oxidative
      stress. Sirtuin 1 is a protein deacetylase that targets endothelial nitric oxide
      synthase resulting in enhanced nitric oxide bioavailability. Although it has been
      highlighted as a potential therapeutic target, we still have no understanding of
      vascular SIRT1 changes during obesity. Therefore, the aim of the present study
      was to measure vascular function, SIRT1 protein levels of expression and markers
      of oxidative stress in obese Zucker rats. Middle cerebral arteries from
      nondiabetic obese and lean Zucker rats were mounted in a pressure myograph to
      assess nitric oxide-dependent dilations. Western blotting was used to measure
      protein levels of SIRT1, p53, acetylated p53, eNOS, phosphorylated eNOS and
      markers of oxidative stress (nitrotyrosine, Nox4 and SOD2) in cerebral vascular
      tissue. SIRT1 expression was two-fold greater in both cerebral arteries and aorta
      from obese compared to lean Zucker rats. Acetylation of p53 at the SIRT1-specific
      lysine 379 site was markedly decreased. At the same time, there was noted
      cerebral vascular impairment however markers of oxidative stress were not
      increased. In fact, Nox4 appeared to be downregulated in obesity. Thus, SIRT1
      protein levels within the vasculature are greater in obese compared to lean
      Zucker rats and are associated with higher SIRT1 activity and lower Nox4
      expression. We propose that the increased expression and activity of SIRT1 may be
      a vascular adaptive mechanism in obesity, aiming to prevent oxidative stress. 

PMID- 24113525
TI  - Effect of the Schiff base complex diaqua-(N-salicylidene-l-glutamato)copper(II)
      monohydrate on human tumor cells.
AB  - The aim of our study was to estimate cytostatic/cytotoxic activity of the
      copper(II) Schiff base complex of the composition [Cu(N-salicylidene-l
      glutamato)(H2O)2].H2O, further Cu(SG-L)H2O, against human colon carcinoma cell
      line HT-29, as well as to determine type of cell death and to find out the
      molecular mechanism of apoptosis induced by this complex. Two highest
      concentrations (50, 100 umol/l) of the complex showed a strong cytotoxic activity
      against human colon carcinoma cells HT-29 after 72 h of influence. Other
      concentrations had a cytostatic activity. Unchelated copper(II) ions and free
      ligands had no effect on the cell growth. Cu(SG-L)H2O preferentially reduced
      cancer cell viability compared to healthy cells (NIH-3T3). Cu(SG-L)H2O induced
      apoptosis of cells HT-29 at all concentrations used (1-100 umol/l) after 48 h of
      influence. Apoptosis was carried out by the mitochondrial pathway with active
      caspases 3 and 9. By the spin-trapping technique combined with electron
      paramagnetic resonance we found that our complex is photochemically stable in
      aqueous systems and does not exhibit radical-scavenging activity when 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonate) cation radical was used as an oxidant.
      The complex exhibits a strong prooxidant property in the initial stages of
      thermal decomposition of K2S2O8 in water solutions leading to the massive
      production of (.)OH radicals. Therefore, this complex could strongly participate
      in anticancer action via a free radical mechanism.

PMID- 24113520
TI  - Nanocarriers for delivery of platinum anticancer drugs.
AB  - Platinum based anticancer drugs have revolutionized cancer chemotherapy, and
      continue to be in widespread clinical use especially for management of tumors of
      the ovary, testes, and the head and neck. However, several dose limiting
      toxicities associated with platinum drug use, partial anti-tumor response in most
      patients, development of drug resistance, tumor relapse, and many other
      challenges have severely limited the patient quality of life. These limitations
      have motivated an extensive research effort towards development of new strategies
      for improving platinum therapy. Nanocarrier-based delivery of platinum compounds
      is one such area of intense research effort beginning to provide encouraging
      preclinical and clinical results and may allow the development of the next
      generation of platinum chemotherapy. This review highlights current understanding
      on the pharmacology and limitations of platinum compounds in clinical use, and
      provides a comprehensive analysis of various platinum-polymer complexes,
      micelles, dendrimers, liposomes and other nanoparticles currently under
      investigation for delivery of platinum drugs.

PMID- 24113526
TI  - Sarcoplasmic reticulum Ca(2+) refilling is determined by L-type Ca(2+) and store
      operated Ca(2+) channels in guinea pig airway smooth muscle.
AB  - Sarcoplasmic reticulum Ca(2+) refilling (SRREF) is crucial to sustain the
      agonists induced airway smooth muscle contraction. Nevertheless, its mechanisms
      have not been clearly described yet, although L-type voltage dependent, store
      operated, receptor operated channels and the Na(+)/Ca(2+) exchanger in its
      reverse mode (NCXREV) have been proposed as Ca(2+) handling proteins
      participating in this process. We found that in guinea pig and bovine tracheal
      smooth muscle, SRREF induced by caffeine was completely abolished by
      thapsigargin, even in the presence of Bay K8644, an activator of the L-type
      Ca(2+) channel. Activation of NCXREV in guinea pig tracheal myocytes increased
      SRREF in ~70%, while opening of the L-type Ca(2+) channels with Bay K8644 and
      favoring the capacitative Ca(2+) entry with 2-APB (32 MUM) also augmented the
      SRREF by ~170% and ~71%, respectively. Methoxyverapamil (D-600, an L-type Ca(2+)
      channel blocker), 2-APB (100 uM, antagonist of the capacitative Ca(2+) entry) and
      PPADS (NCXREV blocker) diminished the SRREF by ~63%, ~72% and ~31%, respectively.
      The simultaneous addition of D-600 and 2-APB annulled SRREF. These last results
      were also seen when carbachol was used instead of caffeine. In tracheal rings, 2
      APB and nifedipine abolished the carbachol-induced contraction. We concluded that
      the sarcoplasmic reticulum Ca(2+) pump is the only mechanism involved in the
      SRREF and that L-type Ca(2+) voltage dependent and store operated Ca(2+) channels
      are the principal membranal Ca(2+) handling proteins that provide extracellular
      Ca(2+) for SRREF and carbachol-induced contraction in the guinea pig airway
      smooth muscle; NCXREV seems to play a minor role.

PMID- 24113527
TI  - Hierarchical modelling of elastic behaviour of human enamel based on synchrotron
      diffraction characterisation.
AB  - Human enamel is a hierarchical mineralized tissue with a two-level composite
      structure. Few studies have focused on the structure-mechanical property
      relationship and its link to the multi-scale architecture of human enamel,
      whereby the response to mechanical loading is affected not only by the rod
      distribution at micro-scale, but also strongly influenced by the mineral
      crystallite shape, and spatial arrangement and orientation. In this study, two
      complementary synchrotron X-ray diffraction techniques, wide and small angle X
      ray scattering (WAXS/SAXS) were used to obtain multi-scale quantitative
      information about the structure and deformation response of human enamel to in
      situ uniaxial compressive loading. The apparent modulus was determined linking
      the external load and the internal strain in hydroxyapatite (HAp) crystallites.
      An improved multi-scale Eshelby model is proposed taking into account the two
      level hierarchical structure of enamel. This framework has been used to analyse
      the experimental data for the elastic lattice strain evolution within the HAp
      crystals. The achieved agreement between the model prediction and experiment
      along the loading direction validates the model and suggests that the new multi
      scale approach reasonably captures the structure-property relationship for the
      human enamel. The ability of the model to predict multi-directional strain
      components is also evaluated by comparison with the measurements. The results are
      useful for understanding the intricate relationship between the hierarchical
      structure and the mechanical properties of enamel, and for making predictions of
      the effect of structural alterations that may occur due to the disease or
      treatment on the performance of dental tissues and their artificial replacements.

PMID- 24113528
TI  - Understanding specificity of the mycosin proteases in ESX/type VII secretion by
      structural and functional analysis.
AB  - Mycobacteria use specialized ESX secretion systems to transport proteins across
      their cell membranes in order to manipulate their environment. In pathogenic
      Mycobacterium tuberculosis there are five paralogous ESX secretion systems, named
      ESX-1 through ESX-5. Each system includes a subtilisin-like protease (mycosin or
      MycP) as a core component essential for secretion. Here we report crystal
      structures of MycP1 and MycP3, the mycosins expressed by the ESX-1 and ESX-3
      systems, respectively. In both mycosins the putative propeptide wraps around the
      catalytic domain and does not occlude the active site. The extensive contacts
      between the putative propeptide and catalytic domain, which include a disulfide
      bond, suggest that the N-terminal extension is an integral part of the active
      mycosin. The catalytic residues of MycP1 and MycP3 are located in a deep active
      site groove in contrast with an exposed active site in majority of subtilisins.
      We show that MycP1 specifically cleaves ESX-1 secretion-associated protein B
      (EspB) in vitro at residues Ala358 and Ala386. We also systematically
      characterize the specificity of MycP1 using peptide libraries, and show that it
      has evolved a narrow specificity relative to other subtilisins. Finally,
      comparison of the MycP1 and MycP3 structures suggest that both enzymes have
      stringent and different specificity profiles that result from the structurally
      distinct active site pockets, which could explain the system specific functioning
      of these proteases. 

PMID- 24113530
TI  - Intraosseous vascular access for alert patients:.
AB  - Nurses are often faced with the challenge of starting an IV line in a patient who
      is dehydrated, has suffered trauma, or is in shock. Even the efforts of the most
      skilled clinician may fail, while valuable time is lost. Intraosseous access is a
      rapid, safe, and effective route for delivering fluids and medications, and is
      recommended by numerous professional and specialty organizations for both
      pediatric and adult patients. Yet many clinicians remain unaware of the
      procedure. This article outlines the procedure and devices used, describes
      support for use in the literature, and discusses various considerations and
      nursing implications.

PMID- 24113529
TI  - Web-based visualisation and analysis of 3D electron-microscopy data from EMDB and
      PDB.
AB  - The Protein Data Bank in Europe (PDBe) has developed web-based tools for the
      visualisation and analysis of 3D electron microscopy (3DEM) structures in the
      Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB). The tools
      include: (1) a volume viewer for 3D visualisation of maps, tomograms and models,
      (2) a slice viewer for inspecting 2D slices of tomographic reconstructions, and
      (3) visual analysis pages to facilitate analysis and validation of maps,
      tomograms and models. These tools were designed to help non-experts and experts
      alike to get some insight into the content and assess the quality of 3DEM
      structures in EMDB and PDB without the need to install specialised software or to
      download large amounts of data from these archives. The technical challenges
      encountered in developing these tools, as well as the more general considerations
      when making archived data available to the user community through a web
      interface, are discussed. 

PMID- 24113531
TI  - Routine dyspnea assessment on unit admission.
AB  - Dyspnea assessment is valuable in diagnosis, prognosis, symptom management, and
      targeted intervention, and in the allotment and management of patient care
      resources. The assessment of dyspnea, like that of pain, depends on patient self
      report. Expert consensus panels have called for dyspnea to be measured
      quantitatively and documented on a routine basis, as is the practice with pain.
      But little information is available on how to measure and record dyspnea ratings
      systematically. Consequently, the prevalence of dyspnea in hospital settings may
      be greater than is generally recognized, and dyspnea may be insufficiently
      managed. This article describes a pilot study that sought to test the feasibility
      of measuring dyspnea as part of the initial patient assessment performed by
      nurses within several inpatient units of a large urban hospital.

PMID- 24113535
TI  - Estimating farm to catchment nutrient fluxes using dynamic simulation modelling-
      can agri-environmental BMPs really do the job?
AB  - A dynamic model of Phosphorus (P) movement through the Peel-Harvey catchment in
      South Western Australia was developed using system dynamics modelling software.
      The model was developed to illustrate watershed P flux and to predict future P
      loss rates under a range of management scenarios. Model input parameters were
      sourced from extensive surveys of local agricultural practices and regional soil
      testing data. Model P-routing routines were developed from the known interactions
      between the various watershed P compartments and fluxes between the various P
      stores. Phosphorus-retention characteristics of a variety of management practices
      were determined from local field trials where available and published values
      where not. The model simulated a 200 year time frame to reflect 100 years to the
      present day since initial land development, and forecast 100 years into the
      future. Although the catchment has an annual P-loss target of 70 tonnes per annum
      (tpa), the measured (and modelled) present-day loss is double this amount (140
      tpa) and this is projected to rise to 1300 tpa if current land management
      practices continue. Broad implementation of neither "biological" BMPs such as
      perennial pastures and managed riparian zones, or of "chemical" BMPs such as
      reduced water solubility fertilisers and P-retentive soil amendments, produces
      reductions in P-loss from present-day levels. Even if broad-scale implementation
      of the large suite of BMPs tested in this research occurs, catchment P-losses are
      likely to increase from the present level of 140 tpa to approximately 200 tpa
      over the next 100 years. This has significant implications for both future land
      use and subsequent water quality in the catchment as well as questioning the
      wisdom and perceptions of efficacy of past and future BMP implementation
      strategies. 

PMID- 24113536
TI  - Comparative performance of free surface and sub-surface flow systems in the
      phytoremediation of hydrocarbons using Scirpus grossus.
AB  - Two types of flow system, free surface flow (FSF) and sub-surface flow (SSF),
      were examined to select a better way to remove total petroleum hydrocarbons (TPH)
      using diesel as a hydrocarbon model in a phytotoxicity test to Scirpus grossus.
      The removal efficiencies of TPH for the two flow systems were compared. Several
      wastewater parameters, including temperature (T,  degrees C), dissolved oxygen
      (DO, mgL(-1)), oxidation-reduction potential (ORP, mV), and pH were recorded
      during the experimental runs. In addition, overall plant lengths, wet weights,
      and dry weights were also monitored. The phytotoxicity test using the bulrush
      plant S. grossus was run for 72 days with different diesel concentrations (1%,
      2%, and 3%) (Vdiesel/Vwater). A comparison between the two flow systems showed
      that the SSF system was more efficient than the FSF system in removing TPH from
      the synthetic wastewater, with average removal efficiencies of 91.5% and 80.2%,
      respectively. The SSF system was able to tolerate higher diesel concentrations
      than was the FSF system.

PMID- 24113537
TI  - Strong heterogeneity in mutation rate causes misleading hallmarks of natural
      selection on indel mutations in the human genome.
AB  - Elucidating the mechanisms of mutation accumulation and fixation is critical to
      understand the nature of genetic variation and its contribution to genome
      evolution. Of particular interest is the effect of insertions and deletions
      (indels) on the evolution of genome landscapes. Recent population-scaled
      sequencing efforts provide unprecedented data for analyzing the relative impact
      of selection versus nonadaptive forces operating on indels. Here, we combined
      McDonald-Kreitman tests with the analysis of derived allele frequency spectra to
      investigate the dynamics of allele fixation of short (1-50 bp) indels in the
      human genome. Our analyses revealed apparently higher fixation probabilities for
      insertions than deletions. However, this fixation bias is not consistent with
      either selection or biased gene conversion and varies with local mutation rate,
      being particularly pronounced at indel hotspots. Furthermore, we identified an
      unprecedented number of loci with evidence for multiple indel events in the
      primate phylogeny. Even in nonrepetitive sequence contexts (a priori not prone to
      indel mutations), such loci are 60-fold more frequent than expected according to
      a model of uniform indel mutation rate. This provides evidence of as yet
      unidentified cryptic indel hotspots. We propose that indel homoplasy, at known
      and cryptic hotspots, produces systematic errors in determination of ancestral
      alleles via parsimony and advise caution interpreting classic selection tests
      given the strong heterogeneity in indel rates across the genome. These results
      will have great impact on studies seeking to infer evolutionary forces operating
      on indels observed in closely related species, because such mutations are
      traditionally presumed homoplasy-free. 

PMID- 24113538
TI  - Modeling gene expression evolution with an extended Ornstein-Uhlenbeck process
      accounting for within-species variation.
AB  - Much of the phenotypic variation observed between even closely related species
      may be driven by differences in gene expression levels. The current availability
      of reliable techniques like RNA-Seq, which can quantify expression levels across
      species, has enabled comparative studies. Ornstein-Uhlenbeck (OU) processes have
      been proposed to model gene expression evolution as they model both random drift
      and stabilizing selection and can be extended to model changes in selection
      regimes. The OU models provide a statistical framework that allows comparisons of
      specific hypotheses of selective regimes, including random drift, constrained
      drift, and expression level shifts. In this way, inferences may be made about the
      mode of selection acting on the expression level of a gene. We augment this model
      to include within-species expression variance, allowing for modeling of
      nonevolutionary expression variance that could be caused by individual genetic,
      environmental, or technical variation. Through simulations, we explore the
      reliability of parameter estimates and the extent to which different selective
      regimes can be distinguished using phylogenies of varying size using both the
      typical OU model and our extended model. We find that if individual variation is
      not accounted for, nonevolutionary expression variation is often mistaken for
      strong stabilizing selection. The methods presented in this article are
      increasingly relevant as comparative expression data becomes more available and
      researchers turn to expression as a primary evolving phenotype. 

PMID- 24113539
TI  - Efficacy of verapamil as an adjunctive treatment in children with drug-resistant
      epilepsy: a pilot study.
AB  - PURPOSE: Verapamil, a voltage-gated calcium channel blocker, has been
      occasionally reported to have some effect on reducing seizure frequency in drug
      resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of
      verapamil as add-on treatment in children with drug-resistant epilepsy. METHODS:
      Seven children with drug-resistant structural-metabolic, unknown or genetic
      (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to
      baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of
      1mg/kg/day and titrated up to 1.5mg/kg/day. After completing the titration
      period, patients entered a 14-month maintenance period and were followed up at 3,
      8, and 14 months. Heart monitoring was performed at baseline and at each follow
      up. The primary outcome measure was the response of seizures to verapamil.
      RESULTS: Three subjects with genetically determined DS showed a partial
      (reduction of 50-99%) response for all types of seizures. A patient with DS
      without known mutation showed a partial control of all types of seizures in the
      first 13 months; then seizures worsened and verapamil was suspended. Two patients
      with structural epilepsy and one with Lennox-Gastaut syndrome showed no
      improvement. Any side effects were recorded. CONCLUSIONS: Add-on treatment with
      verapamil seems to have some effect in controlling seizures in patients with
      genetically determined DS. Our observations justify further research on the
      relationship between calcium channels, calcium channel blockers, and
      channelopathies.

PMID- 24113540
TI  - Use of ipilimumab in the treatment of melanoma.
AB  - Ipilimumab is a monoclonal antibody directed against cytotoxic T-lymphocyte
      antigen-4 that has been approved by the US Food and Drug Administration for the
      treatment of metastatic melanoma. Phase III trials have demonstrated an overall
      survival benefit with its use when compared with standard treatments and other
      investigational therapies. However, the drug poses a notable challenge, given its
      propensity for toxicity, and requires close surveillance when administered in
      clinical practice. This review discusses the mechanism of action for ipilimumab,
      its preclinical data, and the clinical trials that led to its approval by the
      Food and Drug Administration in 2011. 

PMID- 24113542
TI  - Catalytic activity of NiMnO3 for visible light-driven and electrochemical water
      oxidation.
AB  - NiMnO3 was found to be an efficient catalyst for light-driven water oxidation
      using [Ru(bpy)3](2+) and S2O8(2-) as a photosensitiser and a sacrificial oxidant,
      respectively. NiMnO3 exhibited remarkably high catalytic activity in comparison
      with manganese oxides and nickel oxide. For electrochemical water oxidation, the
      highest catalytic current was also obtained with NiMnO3 among the manganese
      oxides. 

PMID- 24113541
TI  - Attenuation of systemic morphine-induced analgesia by central administration of
      ghrelin and related peptides in mice.
AB  - Ghrelin, an acylated 28-amino peptide secreted in the gastric endocrine cells,
      has been demonstrated to stimulate the release of growth hormone, increase food
      intake, and inhibit pro-inflammatory cascade, etc. Ghrelin mainly combines with
      its receptor (GHS-R1alpha) to play the role in physiological and pathological
      functions. It has been reported that ghrelin plays important roles in the control
      of pain through interaction with the opioid system in inflammatory pain and acute
      pain. However, very few studies show the effect of supraspinal ghrelin system on
      antinociception induced by intraperitoneal (i.p.) administration of morphine. In
      the present study, intracerebroventricular (i.c.v.) injection of ghrelin (0.1, 1,
      10 and 100 nmol/L) produced inhibition of systemic morphine (6 mg/kg, i.p.)
      analgesia in the tail withdrawal test. Similarly, i.c.v. injection GHRP-6 and
      GHRP-2 which are the agonists of GHS-R1alpha, also decreased analgesia effect
      induced by morphine injected intraperitoneally in mice. Furthermore, these anti
      opioid activities of ghrelin and related peptides were not blocked by
      pretreatment with the GHS-R1alpha selective antagonist [d-Lys(3)]-GHRP-6 (100
      nmol/L, i.c.v.). These results demonstrated that central ghrelin and related
      peptides could inhibit the analgesia effect induced by intraperitoneal (i.p.)
      administration of morphine. The anti-opioid effects of ghrelin and related
      peptides do not interact with GHS-R1a. These findings may pave the way for a new
      strategy on investigating the interaction between ghrelin system and opioids on
      pain modulation.

PMID- 24113544
TI  - Association between erythrocyte n-3 polyunsaturated fatty acids and biomarkers of
      inflammation and oxidative stress in patients with and without depression.
AB  - Associations between n-3 polyunsaturated fatty acids (PUFAs), inflammation,
      oxidative stress and the risk of depression have been suggested. We hypothesize
      that erythrocyte n-3 PUFAs are inversely associated with biomarkers for
      inflammation and oxidative stress in Koreans with and without depression. Study
      participants comprised 80 cases diagnosed with depression based on the Center for
      Epidemiological Studies Depression Scale Korea version (CES-D-K) scores >=25 and
      psychiatrist confirmation and 80 age- and sex-matched healthy controls without
      histories of depression. Depressed patients had lower levels of n-3 PUFAs and
      higher circulating levels of inducible nitric oxide synthase (iNOS), superoxide
      dismutase, interferon-gamma, and nitrotyrosine compared to the controls. CES-D-K
      scores and levels of iNOS and tumor necrosis factor (TNF)-alpha were negatively
      associated with Omega-3 Index (erythrocyte levels of eicosapentaenoic acid and
      docosahexaenoic acid) after adjusting for confounding factors. Concentrations of
      iNOS, TNF-alpha, thiobarbituric acid reactive substances, and nitrotyrosine were
      negatively correlated with erythrocyte levels of n-3 PUFAs, but positively with
      erythrocyte levels of n-6 PUFAs. Erythrocyte levels of n-3 PUFAs were inversely
      associated with circulating markers of inflammation and oxidative stress in
      Koreans with and without depression in this case control study. Future randomized
      controlled trials are needed to determine whether dietary or supplemental n-3
      PUFAs can reduce inflammation and oxidative stress, and reduce depressive
      symptoms in humans. 

PMID- 24113543
TI  - One-step microfluidic generation of pre-hatching embryo-like core-shell
      microcapsules for miniaturized 3D culture of pluripotent stem cells.
AB  - A novel core-shell microcapsule system is developed in this study to mimic the
      miniaturized 3D architecture of pre-hatching embryos with an aqueous liquid-like
      core of embryonic cells and a hydrogel-shell of zona pellucida. This is done by
      microfabricating a non-planar microfluidic flow-focusing device that enables one
      step generation of microcapsules with an alginate hydrogel shell and an aqueous
      liquid core of cells from two aqueous fluids. Mouse embryonic stem (ES) cells
      encapsulated in the liquid core are found to survive well (>92%). Moreover, ~20
      ES cells in the core can proliferate to form a single ES cell aggregate in each
      microcapsule within 7 days while at least a few hundred cells are usually needed
      by the commonly used hanging-drop method to form an embryoid body (EB) in each
      hanging drop. Quantitative RT-PCR analyses show significantly higher expression
      of pluripotency marker genes in the 3D aggregated ES cells compared to the cells
      under 2D culture. The aggregated ES cells can be efficiently differentiated into
      beating cardiomyocytes using a small molecule (cardiogenol C) without complex
      combination of multiple growth factors. Taken together, the novel 3D microfluidic
      and pre-hatching embryo-like microcapsule systems are of importance to facilitate
      in vitro culture of pluripotent stem cells for their ever-increasing use in
      modern cell-based medicine.

PMID- 24113546
TI  - Impact of blend ratio on the co-firing of a commercial torrefied biomass and coal
      via analysis of oxidation kinetics.
AB  - Incorporation of torrefied biomass into coal-fired power plants could potentially
      lower the SOx and net CO2 emissions resulting from electricity generation.
      However, concerns over lower heating values and slightly higher ash content of
      torrefied biomass suggest that blending it with coal in industrial boilers may be
      preferable to complete fuel transition. By studying the oxidation kinetics of
      coal-torrefied biomass blends in a thermogravimetric analyzer at a heating rate
      of 100 degrees C/min, we find an additive nature among the fuels for peak mass
      loss rates and enthalpies of combustion. The activation energy required to
      initiate decomposition decreases from 132.6 to 77.6 kJ/mol as the torrefied
      biomass increases from 0 to 100 wt%, with a sharp decrease between 0 and 40 wt%.
      Data suggest that incorporation of torrefied biomass into coal-fired boilers is
      dependent on the ability to sacrifice heating value for the lower emissions of
      SOx and net CO2 garnered using bio-coal.

PMID- 24113545
TI  - Eicosanoid post-mortem induction in kidney tissue is prevented by microwave
      irradiation.
AB  - Previously, we, and others, have demonstrated a rapid and significant post-mortem
      increase in brain prostanoid (PG) levels analyzed without microwave fixation, and
      this is not the result of PG trapping or destruction in microwave-irradiated
      brain tissue. In the present study, we demonstrate a dramatic increase in kidney
      eicosanoid levels when analyzed without microwave fixation which was mainly
      accounted for by the 142-, 81-, and 62-fold increase in medullary 6
      ketoPGF1alpha, PGE2, and PGF2alpha, levels, respectively, while PGD2 and TXB2
      levels were increased ~7-fold. Whole kidney and cortex PG were also significantly
      increased in non-microwaved tissue, but at lesser extent. Arachidonic acid and
      the lipoxygenase products hydroxyeicosatetraenoic acids (HETE) were also induced
      in whole kidney, cortex, and medulla 1.5- to 5.5-fold depending upon tissue and
      metabolite. Cyclooxygenase inhibition with indomethacin decreased PG mass in non
      microwaved tissue to basal levels, however HETE and arachidonic acid were not
      decreased. These data demonstrate the critical importance of kidney tissue
      fixation to limiting artifacts during kidney eicosanoid analysis. 

PMID- 24113547
TI  - Production of acetol from glycerol using engineered Escherichia coli.
AB  - Escherichia coli Lin43 is a strain which has some mutations in glycerol kinase
      (GlpK) and the repressor for the glycerol 3-phosphate regulon (GlpR). When
      exposed to glycerol, it quickly accumulates lethal levels of methylglyoxal, which
      is a precursor of acetol; acetol is important for the manufacture of polyols,
      acrolein, dyes, and skin tanning agents. This work reports the engineering of E.
      coli Lin 43 for the conversion of glycerol into acetol. First, the glyoxalase
      system was interrupted by deleting the gloA gene, which increased the acetol
      yield by 32%. In addition, the aldehyde reductase YqhD was overexpressed which
      led to an increase of acetol production by 11.4-fold. Acetol production was
      optimized by varying the cell density, glycerol concentration, supplemental
      carbon source, pH and temperature. Under the optimal conditions (OD600=20, 20 g/L
      glycerol, 2g/L succinate, pH 7.0, and 28 degrees C), we obtained 5.4 g/L acetol
      in 21 h.

PMID- 24113548
TI  - The effects of the antibiotics ampicillin, florfenicol, sulfamethazine, and
      tylosin on biogas production and their degradation efficiency during anaerobic
      digestion.
AB  - The impacts of four common animal husbandry antibiotics (ampicillin, florfenicol,
      sulfamethazine, and tylosin) on anaerobic digestion (AD) treatment efficiency and
      the potential for antibiotic degradation during digestion were evaluated.
      Sulfamethazine and ampicillin exhibited no impact on total biogas production up
      to 280 and 350 mg/L, respectively, although ampicillin inhibited biogas
      production rates during early stages of AD. Tylosin reduced biogas production by
      10-38% between 130 and 913 mg/L. Florfenicol reduced biogas by ~ 5%, 40% and 75%
      at 6.4, 36 and 210 mg/L, respectively. These antibiotic concentrations are higher
      than commonly seen for mixed feedlot manure, so impacts on full scale AD should
      be minimal. Antibiotic degradation products were found, confirming AD effectively
      degraded ampicillin, florfenicol, and tylosin, although some products were
      persistent throughout the process. Contamination of AD solid and liquid effluents
      with sulfamethazine and antibiotic transformation products from florfenicol and
      tylosin could present an environmental concern.

PMID- 24113550
TI  - Local treatment of oligometastatic recurrence in patients with resected non-small
      cell lung cancer.
AB  - OBJECTIVES: We previously reported a retrospective study indicating the
      prognostic impact of the local treatment of oligometastatic recurrence after a
      complete resection for non-small cell lung cancer (NSCLC). In the present study,
      we prospectively observed postoperative oligometastatic patients and investigated
      the effects of local treatment on progression-free survival (PFS). METHODS: Using
      a prospectively maintained database of patients with completely resected NSCLC
      treated between October 2007 and December 2011, we identified 52 consecutive
      patients with postoperative recurrence, excluding second primary lung cancer. Of
      these patients, 31 suffering from distant metastases alone without primary site
      recurrence were included in this study. According to the definition of
      'oligometastases' as a limited number of distant metastases ranging from one to
      three, 17 patients had oligometastatic disease. Of those 17 patients, four
      patients with only brain metastasis were excluded from the analysis. RESULTS: The
      oligometastatic sites included the lungs in five patients, bone in four patients,
      the lungs and brain in two patients, the adrenal glands in one patient and soft
      tissue in one patient. Eleven of the 13 patients first received local treatment.
      Three patients (lung, adrenal gland, soft tissue) underwent surgical resection,
      and the remaining eight patients received radiotherapy. The median PFS was 20
      months in the oligometastatic patients who received local treatment. There were
      five patients with a PFS of longer than two years. The metastatic sites in these
      patients varied, and one patient had three lesions. On the other hand, the two
      remaining patients first received a systemic chemotherapy of their own selection.
      The PFS of these two patients was five and 15 months, respectively. CONCLUSION:
      Local therapy is a choice for first-line treatment in patients with postoperative
      oligometastatic recurrence.

PMID- 24113549
TI  - CHK1 levels correlate with sensitization to pemetrexed by CHK1 inhibitors in non
      small cell lung cancer cells.
AB  - OBJECTIVE: Overexpression of checkpoint kinase 1 (CHK1) is associated with poorer
      patient outcome and therapeutic resistance in multiple tumor models. Inhibition
      of CHK1 has been proposed as a strategy to increase the effectiveness of
      chemotherapeutic agents, especially in p53-deficient tumors. In this study, we
      evaluated the effects of a novel CHK1 inhibitor, MK-8776, in combination with
      pemetrexed (PMX) on cell proliferation and survival in a panel of p53 mutant non
      small cell lung cancer (NSCLC) cell lines. METHODS: We examined CHK1 expression
      in 442 resected lung adenocarcinoma specimens using Affymetrix U133A gene
      expression arrays. We correlated CHK1 mRNA expression with patient survival,
      tumor differentiation and genomic complexity. We evaluated CHK1 levels in NSCLC
      cell lines and identified four p53 mutant cell lines with variable CHK1
      expression (H1993, H23, H1437 and H1299) based on publicly available gene
      expression data. We confirmed differential CHK1 mRNA and CHK1 protein levels by
      qRT-PCR, ELISA, Western Blot analysis (WB) and immunohistochemistry. We examined
      cell line sensitization to PMX in response to CHK1 inhibition with MK-8776 using
      WST-1 and clonogenic survival assays. RESULTS: We found that elevated CHK1
      expression in primary lung adenocarcinomas correlates with poor tumor
      differentiation and significantly worse patient survival. Tumors with elevated
      CHK1 mRNA levels have a higher number of gene mutations and DNA copy number gain
      or amplifications. CHK1 inhibition by MK-8776 enhances sensitivity of NSCLC cell
      lines to PMX. CHK1 mRNA and protein expression are variable among NSCLC cell
      lines, and cells expressing higher levels of CHK1 protein are more sensitive to
      the CHK1 inhibition by MK-8776 as compared to low CHK1 expressing cells.
      CONCLUSIONS: These findings suggest that CHK1 levels may not only serve as a
      biomarker of poor prognosis in surgically-resected lung adenocarcinomas, but
      could also be a predictive marker for CHK1 inhibitor sensitivity, pending in vivo
      and clinical confirmation.

PMID- 24113551
TI  - An upscaling method for cover-management factor and its application in the loess
      Plateau of China.
AB  - The cover-management factor (C-factor) is important for studying soil erosion. In
      addition, it is important to use sampling plot data to estimate the regional C
      factor when assessing erosion and soil conservation. Here, the loess hill and
      gully region in Ansai County, China, was studied to determine a method for
      computing the C-factor. This C-factor is used in the Universal Soil Loss Equation
      (USLE) at a regional scale. After upscaling the slope-scale computational
      equation, the C-factor for Ansai County was calculated by using the soil loss
      ratio, precipitation and land use/cover type. The multi-year mean C-factor for
      Ansai County was 0.36. The C-factor values were greater in the eastern region of
      the county than in the western region. In addition, the lowest C-factor values
      were found in the southern region of the county near its southern border. These
      spatial differences were consistent with the spatial distribution of the soil
      loess ratios across areas with different land uses. Additional research is needed
      to determine the effects of seasonal vegetation growth changes on the C-factor,
      and the C-factor upscaling uncertainties at a regional scale. 

PMID- 24113552
TI  - [History of leprosy in Reunion Island from the beginning of the 18th century
      until today].
AB  - This article traces the history of leprosy in Reunion from the early eighteenth
      century, which long paralleled the slave trace. Lepers were confined to a
      lazaretto and treated with herbs. Father Raimbault, "doctor" and chaplain of the
      lepers in the middle of the twentieth century, is still honored today. The
      improvement in living standards and the use of sulfones finally resulted in the
      control of leprosy. Nonetheless, from 2005 to 2011, an average of three new cases
      per year were detected among a population of 800,000 inhabitants.

PMID- 24113553
TI  - Histomorphometry and bone mechanical property evolution around different implant
      systems at early healing stages: an experimental study in dogs.
AB  - PURPOSE: Commercial implants differ at macro-, micro-, and nanolevels, which
      makes it difficult to distinguish their effect on osseointegration. The aim of
      this study was to evaluate the early integration of 5 commercially available
      implants (Astra OsseoSpeed, Straumann SLA, Intra-Lock Blossom Ossean, Nobel
      Active, and OsseoFix) by histomorphometry and nanoindentation. MATERIALS AND
      METHODS: Implants were installed in the tibiae of 18 beagle dogs. Samples were
      retrieved at 1, 3, and 6 weeks (n = 6 for each time point) and were
      histologically and nanomechanically evaluated. RESULTS: The results presented
      that both time (P < 0.01) and implant system and time interaction (P < 0.02)
      significantly affected the bone-to-implant contact (BIC). At 1 week, the
      different groups presented statistically different outcomes. No significant
      changes in BIC were noted thereafter. There were no significant differences in
      rank elastic modulus (E) or in rank hardness (H) for time (E: P > 0.80; H: P >
      0.75) or implant system (E: P > 0.90; H: P > 0.85). CONCLUSIONS: The effect of
      different implant designs on osseointegration was evident especially at early
      stages of bone healing.

PMID- 24113554
TI  - Evaluation of possible prognostic factors for the success, survival, and failure
      of dental implants.
AB  - PURPOSE: To analyze the prognostic factors that are associated with the success,
      survival, and failure rates of dental implants. MATERIAL AND METHODS: Data
      including implant sizes, insertion time, implant location, and prosthetic
      treatment of 1656 implants have been collected, and the association of these
      factors with success, survival, and failure of implants was analyzed. RESULTS:
      The success rate was lower for short and maxillary implants. The failure rate of
      maxillary implants exceeded that of mandibular implants, and the failure rate of
      implants that were placed in the maxillary anterior region was significantly
      higher than other regions. The failure rates of implants that were placed 5 years
      ago or more were higher than those that were placed later. CONCLUSIONS: Anterior
      maxilla is more critical for implant loss than other sites. Implants in the
      anterior mandible show better success compared with other locations, and longer
      implants show better success rates. The learning curve of the clinician
      influences survival and success rates of dental implants.

PMID- 24113556
TI  - The relationship between abnormalities of saccadic and manual response times in
      Parkinson's disease.
AB  - BACKGROUND: Clinicians normally use subjective rating scales to estimate the
      impairment of patients with Parkinson's disease (PD). More objective and
      quantitative methods of assessment would greatly aid our understanding of the
      disease. One promising approach is to measure reaction time: the large amount of
      data recorded in a short period provides precise, reproducible evaluation of the
      underlying neural decision processes. Manual evoked reaction times and repetitive
      tapping speed are often used, but differences of experimental design and analysis
      tend to obscure their interpretation. Saccadic latency, in many ways a simpler
      and more standardised task, is also normally affected in PD, but its relation to
      the kind of movement impairment that affects patients' quality of life is less
      obvious. OBJESTIVE: The aim of this study was to evaluate these tasks in detail
      and also see whether their use in combination could provide a better measure than
      each in isolation. METHODS: We compared three reaction time tasks: saccadometry,
      and evoked and spontaneous tapping, using protocols as similar as possible,
      correlating the measurements within a group of PD patients and of age-matched
      controls. RESULTS: Surprisingly, manual and saccadic performance is uncorrelated
      in the normal population; but both are similarly affected by PD. The differences
      between groups are strengthened when the three measures are combined.
      CONCLUSIONS: Saccadic latency can be regarded as an appropriate surrogate for
      more general kinds of motor impairment. The combination of saccadic and manual
      parameters enhances their potential use in quantifying disease status and
      evaluating treatments.

PMID- 24113555
TI  - High-throughput metabolic genotoxicity screening with a fluidic microwell chip
      and electrochemiluminescence.
AB  - A high throughput electrochemiluminescent (ECL) chip was fabricated and
      integrated into a fluidic system for screening toxicity-related chemistry of drug
      and pollutant metabolites. The chip base is conductive pyrolytic graphite onto
      which are printed 64 microwells capable of holding one-MUL droplets. Films
      combining DNA, metabolic enzymes and an ECL-generating ruthenium metallopolymer
      (Ru(II)PVP) are fabricated in these microwells. The system runs metabolic enzyme
      reactions, and subsequently detects DNA damage caused by reactive metabolites.
      The performance of the chip was tested by measuring DNA damage caused by
      metabolites of the well-known procarcinogen benzo[a]pyrene (B[a]P). Liver
      microsomes and cytochrome P450 (cyt P450) enzymes were used with and without
      epoxide hydrolase (EH), a conjugative enzyme required for multi-enzyme
      bioactivation of B[a]P. DNA adduct formation was confirmed by determining
      specific DNA-metabolite adducts using similar films of DNA/enzyme on magnetic
      bead biocolloid reactors, hydrolyzing the DNA, and analyzing by capillary liquid
      chromatography-mass spectrometry (CapLC-MS/MS). The fluidic chip was also used to
      measure IC50-values of inhibitors of cyt P450s. All results show good correlation
      with reported enzyme activity and inhibition assays. 

PMID- 24113557
TI  - Falls in Parkinson disease: analysis of a large cross-sectional cohort.
AB  - BACKGROUND: Falls remain a significant cause of morbidity in PD. Risk factors are
      not well understood. OBJECTIVE: In this study we explore risk factors for falls
      in PD utilizing the cross-sectional, baseline data in the National Parkinson
      Foundation Quality Improvement Initiative (NPF-QII) database. Subjects are being
      followed prospectively, and this study will provide the basis for subsequent
      longitudinal analyses. METHODS: A cross-sectional analysis of data from 2,876
      ambulatory patients with Parkinson disease enrolled in the NPF-QII at 18 sites.
      Main outcome measure was falling history in the 3 months preceding assessment.
      The following were considered as possible predictor variables: age, sex, height,
      weight, body mass index, disease duration, age at disease onset, investigator's
      confidence in the diagnosis, Hoehn and Yahr stage, rest tremor, ability to stand
      unassisted, coexistent pathologies (cardiovascular, respiratory, diabetes,
      cancer, neurological, osteoarthritis, and "other" comorbidities),
      anticholinergics, antidepressants, antipsychotics, cognitive enhancers, deep
      brain stimulation surgery, timed-up-and-go, semantic fluency, and 5 word recall.
      Variables with associations to the outcome measure in univariate analyses were
      analyzed in multivariable models using logistic regression. RESULTS: 37.2% of
      subjects experienced falls. In the multivariable regression model the following
      variables were found to be independently associated with falls: disease duration;
      Hoehn and Yahr stage; absence of rest tremor; cardiovascular, arthritis, or
      "other" comorbidity; antidepressants; deep brain stimulation surgery; timed-up
      and-go; and, semantic fluency. CONCLUSION: Disease duration but not age is
      independently associated with falls in Parkinson disease. Timed-up-and-go
      accurately reflects falls risk. Impaired semantic fluency is independently
      associated with falls, while verbal memory is not. Comorbidities,
      antidepressants, and deep brain stimulation also contribute to falls risk.

PMID- 24113558
TI  - Iron deficiency in parkinsonism: region-specific iron dysregulation in
      Parkinson's disease and multiple system atrophy.
AB  - Alpha synuclein pathology is widespread and found in diverse cell types in
      multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason
      for this differential distribution is unknown. Regional differences in the
      distribution of iron are associated with neurodegenerative diseases, and here we
      characterize the relationship between iron homeostasis proteins and regional
      concentration, distribution and form of iron in MSA and PD. In PD substantia
      nigra, tissue iron and expression of the iron export protein ferroportin
      increased, while the iron storage protein ferritin expression was unchanged. In
      the basis pontis of MSA cases, increased total iron concentration coupled with a
      disproportionate increase in ferritin in dysmorphic microglia and a reduction in
      ferroportin expression. This is supported by isothermal remanent magnetisation
      evidence consistent with elevated concentrations of ferritin-bound iron in MSA
      basis pontis. Conventional opinion holds that excess iron is involved in
      neurodegeneration. Our data support that this may be the case in PD. While region
      specific changes in iron are evident in both PD and MSA, the mechanisms of iron
      dysregulation appear quite distinct, with a failure to export iron from the MSA
      basis pontis coupling with significant intracellular accumulation of ferritin
      iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite
      the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of
      changes in anemia of chronic disease, and our preliminary data, coupled with the
      widespread pathology and involvement of multiple cell types, may evidence a
      deficit in bioavailabile iron. 

PMID- 24113560
TI  - A complex association of ABCA7 genotypes with sporadic Alzheimer disease in
      Chinese Han population.
AB  - PURPOSE: Recently, a large genome-wide association study has revealed that
      polymorphism of alleles and genotypes in rs3,764,650 within ABCA7 gene is
      associated with Alzheimer disease in whites. We conducted a case-control study to
      investigate whether these susceptible genetic variants are risk factors for
      sporadic Alzheimer disease (SAD) in Chinese Han population. DESIGN AND METHODS: A
      total of 633 participants consisting of 350 SAD and 283 nondemented elderly
      controls matched for sex and age were recruited and genetic variants in ABCA7
      (rs3,764,650) were genotyped using DNA sequencing. RESULTS: On the basis of
      allele and genotype frequencies in both groups, we found a significant
      association (P=0.004) between ABCA7 genotypes and SAD in Chinese Han population,
      and the results were influenced by age and ApoEepsilon4 status. ApoEepsilon4
      carrier and aging are linked to enhancing ABCA7 risk-associated SAD. However, the
      prevalence of the minor allele G in rs3,764,650 within ABCA7 showed no
      significant difference between the 2 groups in this study. CONCLUSIONS: ABCA7
      (rs3,764,650) was associated with SAD in the Chinese population, with both
      ApoEepsilon4-carrier and aging being factors enhancing its risk.

PMID- 24113559
TI  - Comparison of 2 informant questionnaire screening tools for dementia and mild
      cognitive impairment: AD8 and IQCODE.
AB  - BACKGROUND: Dementia and mild cognitive impairment (MCI) are underrecognized in
      community settings. This may be due in part to the lack of brief dementia
      screening tools available to clinicians. We compared 2 brief, informant-based
      screening tests: the AD8 and the Informant Questionnaire on Cognitive Decline in
      the Elderly (IQCODE) in a community-based neurology practice in the midwestern
      United States. METHODS: We examined 186 consecutive patients (44 controls, 13
      with MCI, and 129 with dementia). Receiver operator characteristic curves were
      used to examine the ability of AD8 and IQCODE to discriminate between controls
      and MCI or dementia. Sensitivity, specificity, predictive values, and likelihood
      ratios were reported. RESULTS: AD8 differentiated healthy controls from MCI
      (P<0.001) or dementia (P<0.001), and MCI from dementia (P=0.008). The IQCODE
      differentiated controls and MCI from dementia (both P<0.001), and between
      controls and MCI (P=0.002). Both AD8 (AUC=0.953; 95% confidence interval, 0.92
      0.99) and IQCODE (AUC=0.930, 95% confidence interval, 0.88-0.97) provided
      discrimination between controls and patients with dementia; however, the AD8 had
      superior sensitivity detecting dementia (99.2%) and MCI (100%) compared with the
      IQCODE (79.1% for dementia, 46.1% for MCI) with nonoverlapping confidence
      intervals. Using published cut-offs (AD8>=2, IQCODE>=3.4), only 1 case of
      dementia was missed with the AD8, whereas the IQCODE failed to detect dementia in
      27 individuals. The AD8 detected MCI in all 13 individuals, whereas the IQCODE
      misclassified 7 individuals. CONCLUSIONS: Both the AD8 and IQCODE were able to
      detect dementia in a community setting. The AD8, however, was more successful
      than IQCODE in detecting MCI. If simple and efficient screening for early
      cognitive impairment is the goal, particularly in the early stages (e.g., for
      prevention trials or public screening), the combination of an informant interview
      (the AD8) and a brief performance measure could be considered as they meet the
      basic requirements of the Personalized Prevention Plan for Medicare
      beneficiaries.

PMID- 24113561
TI  - Medication adherence in patients with dementia: an Austrian cohort study.
AB  - Sustained treatment with effective doses of cholinesterase inhibitors or
      memantine is crucial to transfer treatment effects in dementia. Numerous studies,
      with often small samples sizes, describe low adherence rates. The purpose of
      current study was to examine the medical adherence of antidementia therapy in
      Austria. We analyzed the data of 10 Austrian Health Insurance Funds, including
      treatment-naive dementia patients. Study outcome measures were discontinuation,
      switching, number of days on therapy, Medication-Possession-Ratio, and
      compliance. A total of 15,809 patients (mean age: 79.9 y, female: 67.3%) met the
      study's inclusion criteria. After stratification by index medication there were
      40.3% on donepezil (n=6371); 26.6% on rivastigmine (n=4206); 15.3% on galantamine
      (n=2424); and 17.8% on memantine (n=2808). After 6 and 12 months on therapy, 5376
      (34.0%) and 9243 (58.5%) patients stopped the initially prescribed antidementia
      therapy; after 12 months the highest discontinuation rate was seen for patients
      taking rivastigmine (67.3%), whereas patients on memantine (45.0%) had the
      lowest. After 12 months, a total of 1874 (11.9%) patients switched from their
      index medication to another cholinesterase inhibitor or memantine. A total of
      6163 patients (39.0%) were compliant (Medication-Possession-Ratio >80%) during
      the first 6 months and 5366 patients (33.9%) during 12 months of the study. Our
      study shows that memantine-treated patients adhere significantly better to
      treatment. Specifically, after 12 months, 45.0% discontinued medication, 7.9%
      switched, and 50.8% of patients on therapy were compliant. 

PMID- 24113562
TI  - Social workers' and nurses' illness representations about Alzheimer disease: an
      exploratory study.
AB  - Professionals' perceptions of patients' diseases (illness representations) are a
      major factor influencing the quality of treatment they provide. The aim of the
      study was to examine and compare Alzheimer disease (AD) illness representations
      among 2 main professional groups involved in the care of Alzheimer patients. A
      total of 327 nurses and social workers in Israel were asked to report their
      cognitive representations (dimensions of identity, cause, timeline, consequences,
      control, coherence, timeline cycle) and emotional representations. Knowledge
      about AD, demographic, and occupational characteristics were also obtained.
      Participants perceived AD as a chronic disease associated with severe
      consequences. Statistically significant differences were found between the
      groups, as nurses attributed psychological reasons to AD more than the social
      workers. Nevertheless, social workers perceived AD as more chronic with severe
      consequences compared with the nurses. Despite some resemblance, there were
      differences between the social workers and nurses regarding AD illness
      representations. Therefore, continuing to distribute materials to professionals
      regarding AD is recommended, with attention to the unique characteristics of each
      professional group. Furthermore, the findings encourage the development of
      training and support programs that will not only deal with the organizational and
      instrumental levels of treating AD patients but also with the assessment and
      consequences of professionals' illness representations. 

PMID- 24113563
TI  - Effectiveness of a psychoeducational intervention group program in the reduction
      of the burden experienced by caregivers of patients with dementia: the EDUCA-II
      randomized trial.
AB  - We conducted a multicenter, prospective, evaluator-blinded, 2-arm parallel
      randomized trial to compare the effectiveness of a group psychoeducational
      intervention (PIP) with that of standard care in dementia caregivers. The primary
      outcome was the burden experience evaluated by the Zarit Burden Interview.
      Secondary outcomes were psychological distress evaluated with the scaled General
      Health Questionnaire-28 items, and quality of life evaluated with the Short-Form
      Health Survey 12. Effectiveness endpoint was at 4 months since inception.
      Statistical analyses used complete case and intention-to-treat analysis (ITT).
      The trial recruited 238 caregivers from 22 research sites (115 randomized to PIP,
      123 randomized to standard care). No differences were found in the Zarit Burden
      Interview scores (complete case analysis: mean difference=-1.02, 95% confidence
      interval=-4.41 to 2.37; ITT analysis: MD=-0.55, 95% confidence interval=-3.64 to
      2.55), the Short-Form Health Survey 12 domain scores (all P>0.05), and total
      General Health Questionnaire-28 items scores and some of its subscales (all
      P>0.05) except the anxiety and insomnia subscale for the ITT analysis (P=0.03).
      In summary, PIP in modality of group intervention was not better than standard
      care to reduce caregiver burden and overall psychological distress or to improve
      quality-of-life domains. EDUCA-II trial registry: ISRCTN14411440. 

PMID- 24113564
TI  - Life enhancing activities for family caregivers of people with frontotemporal
      dementia.
AB  - Aberrant psychological and behavioral symptoms are common in patients with
      dementia. These symptoms have negative consequences for family caregivers,
      causing stress and burden. Frontotemporal dementia (FTD) symptoms cause more
      pronounced stress and burden on caregivers than those associated with Alzheimer
      dementia. In this randomized, attention control pilot study, we delivered 5
      weekly, one-on-one, positive affect intervention sessions to family caregivers of
      people with FTD. The program, Life Enhancing Activities for Family Caregivers:
      LEAF was conducted in-person or by videoconference with caregivers across the
      United States. Measures of affect, caregiver mood, stress, distress, and
      caregiver burden were assessed at baseline, end of sessions, and 1 month after
      completion. Twenty-four caregivers (12 intervention and 12 attention control)
      participated. At the end of the intervention, scores on positive affect, negative
      affect, burden, and stress all improved in the intervention compared with the
      control group. These scores continued to show improvement at the assessment done
      1 month after intervention. Subjects were receptive to the skills and the
      delivery methods. The positive emotion skill-building intervention proved
      feasible especially in the internet videoconference delivery format. The
      intervention promoted positive affect and improved psychological outcomes for
      family caregivers of people with FTD. 

PMID- 24113566
TI  - The mechanism of electroacupuncture for predicting the efficacy of deep brain
      stimulation in pharmacoresistant epilepsy may be involved in the
      melanocortinergic signal.

PMID- 24113567
TI  - Magnetoencephalography in the study of epilepsy and consciousness.
AB  - The neural bases of altered consciousness in patients with epilepsy during
      seizures and at rest have raised significant interest in the last decade. This
      exponential growth has been supported by the parallel development of techniques
      and methods to investigate brain function noninvasively with unprecedented
      spatial and temporal resolution. In this article, we review the contribution of
      magnetoencephalography to deconvolve the bioelectrical changes associated with
      impaired consciousness during seizures. We use data collected from a patient with
      refractory absence seizures to discuss how spike-wave discharges are associated
      with perturbations in optimal connectivity within and between brain regions and
      discuss indirect evidence to suggest that this phenomenon might explain the
      cognitive deficits experienced during prolonged 3/s spike-wave discharges.

PMID- 24113568
TI  - Video-electroencephalography investigation of ictal alterations of consciousness
      in epilepsy and nonepileptic attack disorder: practical considerations.
AB  - The ictal assessment of consciousness is of central importance in the
      differential diagnosis of epilepsy and nonepileptic attack disorder (NEAD). Long
      term video-electroencephalography (video-EEG) is currently considered the gold
      standard investigative technique for the evaluation of patients with recurrent
      attacks associated with transient alterations of arousal (responsiveness) and/or
      awareness (experiential states). This paper offers a concise review focusing on
      the practical aspects of clinical relevance in the video-EEG diagnostic workout
      of inpatients with suspected epilepsy or NEAD, as outlined in existing guidelines
      and recommendations. The reviewed literature implies that both implementation of
      specific procedures (e.g., activation maneuvers) and interpersonal approach
      (e.g., monitoring protocols) during video-EEG should be tailored to the
      individual patient's presentation.

PMID- 24113565
TI  - Complex metabolically demanding sensory processing in the olfactory system:
      implications for epilepsy.
AB  - Although the olfactory system is not generally associated with seizures, sharp
      application of odor eliciting activity in a large number of olfactory sensory
      neurons (OSNs) has been shown to elicit seizures. This is most likely due to
      increased ictal activity in the anterior piriform cortex-an area of the olfactory
      system that has limited GABAergic interneuron inhibition of pyramidal output cell
      activity. Such hyperexcitability in a well-characterized and highly accessible
      system makes olfaction a potentially powerful model system to examine
      epileptogenesis.

PMID- 24113569
TI  - The quantitative measurement of consciousness during epileptic seizures.
AB  - The assessment of consciousness is a fundamental element in the classification of
      epileptic seizures. It is, therefore, of great importance for clinical practice
      to develop instruments that enable an accurate and reliable measurement of the
      alteration of consciousness during seizures. Over the last few years, three
      psychometric scales have been specifically proposed to measure ictal
      consciousness: the Ictal Consciousness Inventory (ICI), the Consciousness Seizure
      Scale (CSS), and the Responsiveness in Epilepsy Scale--versions I and II (RES-I
      and RES-II). The ICI is a self-report psychometric instrument which
      retrospectively assesses ictal consciousness along the dimensions of the
      level/arousal and contents/awareness. The CSS has been used by clinicians to
      quantify the impairment of consciousness in order to establish correlations with
      the brain mechanisms underlying alterations of consciousness during temporal lobe
      seizures. The most recently developed observer-rated instrument is the RES-I,
      which has been used to assess responsiveness during epileptic seizures in
      patients undergoing video-EEG. The implementation of standardized psychometric
      tools for the assessment of ictal consciousness can complement clinical
      observations and contribute to improve accuracy in seizure classification.

PMID- 24113570
TI  - Selenium dietary supplementation as a mechanism to restore hepatic selenoprotein
      regulation in rat pups exposed to alcohol.
AB  - Ethanol exposure during gestation and lactation decreases selenium (Se) intake,
      disrupting body Se balance and inducing oxidative stress in rat offspring.
      Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20%
      v/v) dams during gestation and lactation. When the dams' pups were 21 days old,
      the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1
      and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into
      control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS)
      groups. The purpose was to evaluate the effect of the selenium-supplemented diet
      on the levels of Se deposits present in the livers of their pups. Alcohol
      decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol
      increases GPx4 and SelP expression. Se was measured by furnace graphite atomic
      absorption spectrometry, the antioxidant activity of GPx and concentration of
      hepatic phospholipids (PL) were determined by spectrophotometry, and the
      selenoprotein expressions were detected by Western blotting. Selenite treatment
      prevented alcohol's effects of diminishing the Se deposits, GPx activity, and
      GPx1 expression, while maintaining the high levels of the expression of GPx4 and
      SelP. These results suggest that depletion of hepatic Se levels in rat pups,
      caused by ethanol exposure to their dams, affects the synthesis of the 3 main
      hepatic selenoproteins in different ways, which is related to a decrease in GPx
      activity and PL concentration, and an increase in serum Se levels. Selenium
      supplementation to the dams increased the expression of GPx1, GPx4, and SelP in
      their pups.

PMID- 24113572
TI  - Survival after lung transplantation in systemic sclerosis. A systematic review.
AB  - BACKGROUND: Lung transplantation is a life-saving option for systemic sclerosis
      (SSc)-associated pulmonary arterial hypertension (PAH) and interstitial lung
      disease (SSc-ILD) patients. However, some programs may be concerned about the
      possibility of excess post-transplantation mortality related to the extra
      pulmonary manifestations of SSc. The objective of this study was to evaluate
      survival of SSc patients post-lung transplantation. We secondarily evaluated SSc
      lung transplant recipient characteristics (age, sex, and type of SSc lung
      disease), and discussed post-lung transplantation survival of SSc patients and
      non-SSc patients (idiopathic PAH, and ILD). METHODS: A systematic review of
      MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials and CINAHL (all
      inception to 2012) was performed to identify studies evaluating post-lung
      transplant survival in SSc compared to PAH and ILD patients. Two reviewers
      independently abstracted study and survival data. RESULTS: Two hundred twenty-six
      citations were screened to identify 7 observational studies reporting SSc
      patients who underwent single lung, double lung, or heart-lung transplantation.
      Mean age at transplantation ranged 46-53 years. SSc post-transplantation survival
      ranged 69%-91% at 30-days, 69%-85% at 6-months, 59%-93% at 1-year, 49%-80% at 2
      years, and 46%-79% at 3-years. Causes of death included graft failure, infection,
      cardiac events, hemorrhagic stroke, respiratory failure, malignancy, pulmonary
      hypertension, complications of bronchiolitis obliterans syndrome, anesthetic
      complication, and scleroderma renal crisis. There were no reports of recurrence
      of SSc in the lung allograft. CONCLUSION: The short-term and intermediate-term
      survival post-lung transplantation are similar to IPAH and ILD patients requiring
      lung transplantation.

PMID- 24113571
TI  - Septins promote dendrite and axon development by negatively regulating
      microtubule stability via HDAC6-mediated deacetylation.
AB  - Neurite growth requires two guanine nucleotide-binding protein polymers of
      tubulins and septins. However, whether and how those cytoskeletal systems are
      coordinated was unknown. Here we show that the acute knockdown or knockout of the
      pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their
      interhemispheric and cerebrospinal axon projections and dendritogenesis in
      perinatal mice, when the microtubules are severely hyperacetylated. The resulting
      hyperstabilization and growth retardation of microtubules are demonstrated in
      vitro. The phenotypic similarity between SEPT7 depletion and the pharmacological
      inhibition of alpha-tubulin deacetylase HDAC6 reveals that HDAC6 requires SEPT7
      not for its enzymatic activity, but to associate with acetylated alpha-tubulin.
      These and other findings indicate that septins provide a physical scaffold for
      HDAC6 to achieve efficient microtubule deacetylation, thereby negatively
      regulating microtubule stability to an optimal level for neuritogenesis. Our
      findings shed light on the mechanisms underlying the HDAC6-mediated coupling of
      the two ubiquitous cytoskeletal systems during neural development. 

PMID- 24113573
TI  - Siganus oramin recombinant L-amino acid oxidase is lethal to Cryptocaryon
      irritans.
AB  - A novel antimicrobial and antiparasitic protein (APP/SR-LAAO) isolated from serum
      of the rabbitfish (Siganus oramin) was confirmed to be lethal to Cryptocaryon
      irritans, an important marine parasitic ciliate that causes marine white spot
      disease in a variety of wild and cultured fish. In this study, a recombinant SR
      LAAO (rSR-LAAO) was expressed on a large scale in Escherichia coli Rosetta
      gamiTM(DE3)pLysS cells. rSR-LAAO was expressed as an inactive form in the
      inclusion bodies. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay showed that after purification, refolding and
      ultrafiltration, rSR-LAAO had a significantly cytotoxic effect on C. irritans
      theronts. Using light microscopy, scanning electron microscopy and fluorescence
      microscopy, we found that theronts rapidly became weakly motile, cilia became
      detached, cells became rounded, membranes eventually lysed in different cell
      positions and cytoplasmic contents leaked out of the cell. These results
      suggested the recombinant SR-LAAO was significantly lethal to C. irritans and the
      death process of the parasite incubated with rSR-LAAO was remarkably similar
      compared to the SR-LAAO group as reported earlier.

PMID- 24113574
TI  - Substrate stiffness regulates temporary NF-kappaB activation via actomyosin
      contractions.
AB  - Physical properties of the extracellular matrix (ECM) can control cellular
      phenotypes via mechanotransduction, which is the process of translation of
      mechanical stresses into biochemical signals. While current research is
      clarifying the relationship between mechanotransduction and cytoskeleton or
      adhesion complexes, the contribution of transcription factors to
      mechanotransduction is not well understood. The results of this study revealed
      that the transcription factor NF-kappaB, a major regulator for immunoreaction and
      cancer progression, is responsive to substrate stiffness. NF-kappaB activation
      was temporarily induced in H1299 lung adenocarcinoma cells grown on a stiff
      substrate but not in cells grown on a soft substrate. Although the activation of
      NF-kappaB was independent of the activity of integrin beta1, an ECM-binding
      protein, the activation was dependent on actomyosin contractions induced by
      phosphorylation of myosin regulatory light chain (MRLC). Additionally, the
      inhibition of MRLC phosphorylation by Rho kinase inhibitor Y27632 reduced the
      activity of NF-kappaB. We also observed substrate-specific morphology of the
      cells, with cells grown on the soft substrate appearing more rounded and cells
      grown on the stiff substrate appearing more spread out. Inhibiting NF-kappaB
      activation caused a reversal of these morphologies on both substrates. These
      results suggest that substrate stiffness regulates NF-kappaB activity via
      actomyosin contractions, resulting in morphological changes. 

PMID- 24113576
TI  - Rational design, characterization and catalytic application of metal clusters
      functionalized with hydrophilic, chiral ligands: a proof of principle study.
AB  - A proof of principle is presented for the rational design of metal clusters
      functionalized with hydrophilic, chiral ligands. A colloidal method is used to
      prepare "unprotected" metal clusters of well-defined size that are subsequently
      functionalized in a separate step with hydrophilic, chiral ligands. As clusters
      from the same batch are functionalized with different organic molecules while the
      cluster size is maintained, the approach allows for systematic investigations and
      the differences in the observed properties to be related to the influence of the
      functionalizing ligand. Within this work cysteine and two cysteine derivatives
      (glutathione and N-acetyl-cysteine) are used as functionalizing ligands for Pt
      clusters. The materials are characterized using various methods allowing for the
      determination of ligand coverage, binding mode and chiro-optical properties.
      Finally, 2-butanone hydrogenation is used as a simple model reaction to
      demonstrate that these systems exhibit the potential to be used as asymmetric,
      heterogeneous catalysts. The observed differences in selectivity and reactivity
      are discussed based on the knowledge gained from the characterization. 

PMID- 24113575
TI  - Galvanic microparticles increase migration of human dermal fibroblasts in a wound
      healing model via reactive oxygen species pathway.
AB  - Electrical signals have been implied in many biological mechanisms, including
      wound healing, which has been associated with transient electrical currents not
      present in intact skin. One method to generate electrical signals similar to
      those naturally occurring in wounds is by supplementation of galvanic particles
      dispersed in a cream or gel. We constructed a three-layered model of skin
      consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel
      barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic
      of a cream containing galvanic particles applied to skin). Using this model, we
      investigated the effects of the properties and amounts of Cu/Zn galvanic
      particles on adult human dermal fibroblasts in terms of the speed of wound
      closing and gene expression. The collected data suggest that the effects on wound
      closing are due to the ROS-mediated enhancement of fibroblast migration, which is
      in turn mediated by the BMP/SMAD signaling pathway. These results imply that
      topical low-grade electric currents via microparticles could enhance wound
      healing.

PMID- 24113577
TI  - Capture and 3D culture of colonic crypts and colonoids in a microarray platform.
AB  - Crypts are the basic structural and functional units of colonic epithelium and
      can be isolated from the colon and cultured in vitro into multi-cell spheroids
      termed "colonoids". Both crypts and colonoids are ideal building blocks for
      construction of an in vitro tissue model of the colon. Here we proposed and
      tested a microengineered platform for capture and in vitro 3D culture of colonic
      crypts and colonoids. An integrated platform was fabricated from
      polydimethylsiloxane which contained two fluidic layers separated by an array of
      cylindrical microwells (150 MUm diameter, 150 MUm depth) with perforated bottoms
      (30 MUm opening, 10 MUm depth) termed "microstrainers". As fluid moved through
      the array, crypts or colonoids were retained in the microstrainers with a >90%
      array-filling efficiency. Matrigel as an extracellular matrix was then applied to
      the microstrainers to generate isolated Matrigel pockets encapsulating the crypts
      or colonoids. After supplying the essential growth factors, epidermal growth
      factor, Wnt-3A, R-spondin 2 and noggin, 63 +/- 13% of the crypts and 77 +/- 8% of
      the colonoids cultured in the microstrainers over a 48-72 h period formed viable
      3D colonoids. Thus colonoid growth on the array was similar to that under
      standard culture conditions (78 +/- 5%). Additionally the colonoids displayed the
      same morphology and similar numbers of stem and progenitor cells as those under
      standard culture conditions. Immunofluorescence staining confirmed that the
      differentiated cell-types of the colon, goblet cells, enteroendocrine cells and
      absorptive enterocytes, formed on the array. To demonstrating the utility of the
      array in tracking the colonoid fate, quantitative fluorescence analysis was
      performed on the arrayed colonoids exposed to reagents such as Wnt-3A and the
      gamma-secretase inhibitor LY-411575. The successful formation of viable, multi
      cell type colonic tissue on the microengineered platform represents a first step
      in the building of a "colon-on-a-chip" with the goal of producing the physiologic
      structure and organ-level function of the colon for controlled experiments. 

PMID- 24113578
TI  - Sensing at the nanoscale.

PMID- 24113579
TI  - Digit ratio (2D:4D), aggression, and testosterone in men exposed to an aggressive
      video stimulus.
AB  - The relative lengths of the 2(nd) and 4(th) digits (2D:4D) is a negative
      biomarker for prenatal testosterone, and low 2D:4D may be associated with
      aggression. However, the evidence for a 2D:4D-aggression association is mixed.
      Here we test the hypothesis that 2D:4D is robustly linked to aggression in
      "challenge" situations in which testosterone is increased. Participants were
      exposed to an aggressive video and a control video. Aggression was measured after
      each video and salivary free testosterone levels before and after each video.
      Compared to the control video, the aggressive video was associated with raised
      aggression responses and a marginally significant increase in testosterone. Left
      2D:4D was negatively correlated with aggression after the aggressive video and
      the strength of the correlation was higher in those participants who showed the
      greatest increases in testosterone. Left 2D:4D was also negatively correlated to
      the difference between aggression scores in the aggressive and control
      conditions. The control video did not influence testosterone concentrations and
      there were no associations between 2D:4D and aggression. We conclude that 2D:4D
      moderates the impact of an aggressive stimulus on aggression, such that an
      increase in testosterone resulting from a "challenge" is associated with a
      negative correlation between 2D:4D and aggression.

PMID- 24113580
TI  - Changes in women's attractiveness perception of masculine men's dances across the
      ovulatory cycle: preliminary data.
AB  - Women's preferences for putative cues of genetic quality in men's voices, faces,
      bodies, and behavioral displays are stronger during the fertile phase of the
      ovulatory cycle. Here we show that ovulatory cycle-related changes in women's
      attractiveness perceptions of male features are also found with dance movements,
      especially those perceived as highly masculine. Dance movements of 79 British men
      were recorded with an optical motion-capture system whilst dancing to a basic
      rhythm. Virtual humanoid characters (avatars) were created and converted into 15
      second video clips and rated by 37 women on masculinity. Another 23 women judged
      the attractiveness of the 10 dancers who scored highest and those 10 who scored
      lowest on masculinity once in days of high fertility and once in days of low
      fertility of their ovulatory cycle. High-masculine dancers were judged higher on
      attractiveness around ovulation than on other cycle days, whilst no such
      perceptual difference was found for low-masculine dancers. We suggest that women
      may gain fitness benefits from evolved preferences for masculinity cues they
      obtain from male dance movements. 

PMID- 24113582
TI  - Genetic correction of stem cells in the treatment of inherited diseases and focus
      on xeroderma pigmentosum.
AB  - Somatic stem cells ensure tissue renewal along life and healing of injuries.
      Their safe isolation, genetic manipulation ex vivo and reinfusion in patients
      suffering from life threatening immune deficiencies (for example, severe combined
      immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene therapy.
      Similarly, adult epidermal stem cells have the capacity to renew epidermis, the
      fully differentiated, protective envelope of our body. Stable skin replacement of
      severely burned patients have proven life saving. Xeroderma pigmentosum (XP) is a
      devastating disease due to severe defects in the repair of mutagenic DNA lesions
      introduced upon exposure to solar radiations. Most patients die from the
      consequences of budding hundreds of skin cancers in the absence of
      photoprotection. We have developed a safe procedure of genetic correction of
      epidermal stem cells isolated from XP patients. Preclinical and safety
      assessments indicate successful correction of XP epidermal stem cells in the long
      term and their capacity to regenerate a normal skin with full capacities of DNA
      repair. 

PMID- 24113583
TI  - New insights in the pathogenesis of multiple sclerosis--role of acrolein in
      neuronal and myelin damage.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      (CNS) characterized by an inappropriate inflammatory reaction resulting in
      widespread myelin injury along white matter tracts. Neurological impairment as a
      result of the disease can be attributed to immune-mediated injury to myelin,
      axons and mitochondria, but the molecular mechanisms underlying the neuropathy
      remain incompletely understood. Incomplete mechanistic knowledge hinders the
      development of therapies capable of alleviating symptoms and slowing disease
      progression in the long-term. Recently, oxidative stress has been implicated as a
      key component of neural tissue damage prompting investigation of reactive oxygen
      species (ROS) scavengers as a potential therapeutic option. Despite the
      establishment of oxidative stress as a crucial process in MS development and
      progression, ROS scavengers have had limited success in animal studies which has
      prompted pursuit of an alternative target capable of curtailing oxidative stress.
      Acrolein, a toxic beta-unsaturated aldehyde capable of initiating and
      perpetuating oxidative stress, has been suggested as a viable point of
      intervention to guide the development of new treatments. Sequestering acrolein
      using an FDA-approved compound, hydralazine, offers neuroprotection resulting in
      dampened symptom severity and slowed disease progression in experimental
      autoimmune encephalomyelitis (EAE) mice. These results provide promise for
      therapeutic development, indicating the possible utility of neutralizing acrolein
      to preserve and improve neurological function in MS patients. 

PMID- 24113581
TI  - Non-coding RNAs: the "dark matter" of cardiovascular pathophysiology.
AB  - Large-scale analyses of mammalian transcriptomes have identified a significant
      number of different RNA molecules that are not translated into protein. In fact,
      the use of new sequencing technologies has identified that most of the genome is
      transcribed, producing a heterogeneous population of RNAs which do not encode for
      proteins (ncRNAs). Emerging data suggest that these transcripts influence the
      development of cardiovascular disease. The best characterized non-coding RNA
      family is represented by short highly conserved RNA molecules, termed microRNAs
      (miRNAs), which mediate a process of mRNA silencing through transcript
      degradation or translational repression. These microRNAs (miRNAs) are expressed
      in cardiovascular tissues and play key roles in many cardiovascular pathologies,
      such as coronary artery disease (CAD) and heart failure (HF). Potential links
      between other ncRNAs, like long non-coding RNA, and cardiovascular disease are
      intriguing but the functions of these transcripts are largely unknown. Thus, the
      functional characterization of ncRNAs is essential to improve the overall
      understanding of cellular processes involved in cardiovascular diseases in order
      to define new therapeutic strategies. This review outlines the current knowledge
      of the different ncRNA classes and summarizes their role in cardiovascular
      development and disease. 

PMID- 24113584
TI  - Transcriptional regulation of a chitinase gene by 20-hydroxyecdysone and
      starvation in the oriental fruit fly, Bactrocera dorsalis.
AB  - Insect chitinases are hydrolytic enzymes that are required for the degradation of
      glycosidic bonds of chitin. In this study, we identified and characterized a full
      length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera
      dorsalis. The cDNA contains an open reading frame (ORF) of 1449 bp that encodes
      483 amino acid residues and 126- and 296-bp non-coding regions at the 5'- and 3'
      ends, respectively. The BdCht2 genome has four exons and three introns. The
      predicted molecular mass of the deduced BdCht2 is approximately 54.3 kDa, with an
      isoelectric point of 5.97. The 977 bp 5' flanking region was identified and the
      transcription factor binding sites were predicted. Bioinformatic analyses showed
      that the deduced amino acid sequence of BdCht2 had 34%-66% identity to that of
      chitinases identified in other insect species. Quantitative real-time PCR (qPCR)
      analyses indicated that BdCht2 was mainly expressed during the larval-pupal and
      pupal-adult transitions. The tissue-specific expression showed that the highest
      expression was in the integument, followed by the fat body and other tissues.
      Moreover, the expression of BdCht2 was upregulated significantly upon 20
      hydroxyecdysone (20E) at different dose injections after 8 h compared to that of
      the control. Starvation also increased the expression of BdCht2 in the third
      instar larvae and was suppressed again by re-feeding the insects. These results
      suggest that BdCht2 plays an important role in the molting process of B. dorsalis
      larvae and can be regulated by 20E. 

PMID- 24113585
TI  - Marine polysaccharide networks and diatoms at the nanometric scale.
AB  - Despite many advances in research on photosynthetic carbon fixation in marine
      diatoms, the biophysical and biochemical mechanisms of extracellular
      polysaccharide production remain significant challenges to be resolved at the
      molecular scale in order to proceed toward an understanding of their functions at
      the cellular level, as well as their interactions and fate in the ocean. This
      review covers studies of diatom extracellular polysaccharides using atomic force
      microscopy (AFM) imaging and the quantification of physical forces. Following a
      brief summary of the basic principle of the AFM experiment and the first AFM
      studies of diatom extracellular polymeric substance (EPS), we focus on the
      detection of supramolecular structures in polysaccharide systems produced by
      marine diatoms. Extracellular polysaccharide fibrils, attached to the diatom cell
      wall or released into the surrounding seawater, form distinct supramolecular
      assemblies best described as gel networks. AFM makes characterization of the
      diatom polysaccharide networks at the micro and nanometric scales and a clear
      distinction between the self-assembly and self-organization of these complex
      systems in marine environments possible. 

PMID- 24113586
TI  - Disease animal models of TDP-43 proteinopathy and their pre-clinical
      applications.
AB  - Frontotemperal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)
      are two common neurodegenerative diseases. TDP-43 is considered to be a major
      disease protein in FTLD/ALS, but it's exact role in the pathogenesis and the
      effective treatments remains unknown. To address this question and to determine a
      potential treatment for FTLD/ALS, the disease animal models of TDP-43
      proteinopathy have been established. TDP-43 proteinopathy is the histologic
      feature of FTLD/ALS and is associated with disease progression. Studies on the
      disease animal models with TDP-43 proteinopathy and their pre-clinical
      applications are reviewed and summarized. Through these disease animal models,
      parts of TDP-43 functions in physiological and pathological conditions will be
      better understood and possible treatments for FTLD/ALS with TDP-43 proteinopathy
      may be identified for possible clinical applications in the future. 

PMID- 24113588
TI  - Determination of homoarginine, arginine, NMMA, ADMA, and SDMA in biological
      samples by HPLC-ESI-mass spectrometry.
AB  - N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-methyl-L-arginine (NMMA) are
      endogenous inhibitors of nitric oxide synthase (NOS). In contrast, N(G),N'(G)
      dimethyl-L-arginine (SDMA) possesses only a weak inhibitory potency towards
      neuronal NOS and it is known to limit nitric oxide (NO) production by competing
      with L-arginine for cellular uptake. The inhibition of NOS is associated with
      endothelial dysfunction in cardiovascular diseases as well in chronic renal
      failure. L-homoarginine (HArg), a structural analog of L-arginine (Arg), is an
      alternative but less efficient substrate for NOS. Besides, it inhibits arginase,
      leading to an increased availability of L-arginine for NOS to produce NO.
      However, its relation with cardiovascular disease remains unclear. To date,
      several analytical methods for the quantitative determination of Arg, HArg, NMMA,
      AMDA, and SDMA in biological samples have been described. Here, we present a
      simple, fast, and accurate HPLC-ESI-MS/MS method which allows both the
      simultaneous determination and quantification of these compounds without needing
      derivatization, and the possibility to easily modulate the chromatographic
      separation between HArg and NMMA (or between SDMA and ADMA). Data on biological
      samples revealed the feasibility of the method, the minimal sample preparation,
      and the fast run time which make this method very suitable and accurate for
      analysis in the basic and clinical settings.

PMID- 24113587
TI  - Role of hepatic progenitor cells in nonalcoholic fatty liver disease development:
      cellular cross-talks and molecular networks.
AB  - Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging
      from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may
      progress to cirrhosis and hepatocellular carcinoma. NASH has been independently
      correlated with atherosclerosis progression and cardiovascular risk. NASH
      development is characterized by intricate interactions between resident and
      recruited cells that enable liver damage progression. The increasing general
      agreement is that the cross-talk between hepatocytes, hepatic stellate cells
      (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid
      homeostasis, insulin resistance, danger recognition, immune tolerance response
      and fibrogenesis. Moreover, several evidences have suggested that hepatic
      stem/progenitor cell (HPCs) activation is a component of the adaptive response of
      the liver to oxidative stress in NAFLD. HPC activation determines the appearance
      of a ductular reaction. In NASH, ductular reaction is independently correlated
      with progressive portal fibrosis raising the possibility of a periportal
      fibrogenetic pathway for fibrogenesis that is parallel to the deposition of
      subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that
      adipokines, a class of circulating factors, have a key role in the cross-talk
      among HSCs, HPCs and liver macrophages. This review will be focused on cellular
      cross-talk and the relative molecular networks which are at the base of NASH
      progression and fibrosis. 

PMID- 24113590
TI  - Thermal diffusion of 67Ga from irradiated Zn targets.
AB  - Gallium-67 is a cyclotron produced radionuclide and 67Ga-citrate complex scans
      are performed in a variety of applications in Nuclear Medicine. The aim of this
      study was to evaluate a new method for the chemical separation of 67Ga from Zn
      targets. The method has 2 steps, first the thermal diffusion of 67Ga with
      concentrated acetic acid and then purification by cation exchange in ammonium
      medium. The final 67Ga solution was obtained in 0.1 mol L-1 HCl with the
      desirable high purity.

PMID- 24113589
TI  - Characterization of apoptosis induced by emodin and related regulatory mechanisms
      in human neuroblastoma cells.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb,
      has a wide range of therapeutic applications. Recent studies have shown that
      emodin can induce or prevent cell apoptosis, although the precise molecular
      mechanisms underlying these effects are unknown. Experiments from the current
      study revealed that emodin (10-20 MUM) induces apoptotic processes in the human
      neuroblastoma cell line, IMR-32, but exerts no injury effects at treatment doses
      below 10 MUM. Treatment with emodin at concentrations of 10-20 MUM led to a
      direct increase in the reactive oxygen species (ROS) content in IMR-32 cells,
      along with significant elevation of cytoplasmic free calcium and nitric oxide
      (NO) levels, loss of mitochondrial membrane potential (MMP), activation of
      caspases-9 and -3, and cell death. Pretreatment with nitric oxide (NO) scavengers
      suppressed the apoptotic biochemical changes induced by 20 MUM emodin, and
      attenuated emodin-induced p53 and p21 expression involved in apoptotic signaling.
      Our results collectively indicate that emodin at concentrations of 10-20 MUM
      triggers apoptosis of IMR-32 cells via a mechanism involving both ROS and NO.
      Based on the collective results, we propose a model for an emodin-triggered
      apoptotic signaling cascade that sequentially involves ROS, Ca2+, NO, p53,
      caspase-9 and caspase-3.

PMID- 24113591
TI  - IVF endocrinology: the Edwards era.
AB  - Through pioneering human IVF as a global infertility treatment, Robert Edwards
      and his clinical partner Patrick Steptoe launched the field of IVF endocrinology.
      Following repeated failures with oocytes collected in human menopausal
      gonadotrophin (HMG) primed cycles timed to injection of human chorionic
      gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous
      menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory
      follicular development and collect a single ripe egg timed to the natural LH
      surge. Despite this groundbreaking achievement, ovulation induction was clearly
      required to make IVF treatment clinically robust and reliable. Ovarian
      stimulation with clomiphene citrate was used to achieve the first maternity from
      a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully
      introduced-including substitution of 'pure' follicle-stimulating hormone as the
      principal ovarian stimulant. The application and success of IVF treatment were
      dramatically enhanced by the introduction of gonadotrophin-releasing hormone
      analogues that enabled elective control of endogenous gonadotrophin release
      during ovarian stimulation. Programmed gonadotrophin regimes yielding double
      digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards
      expressed increasing concern over the cost, complexity and potential long-term
      health risks of such high-order ovarian stimulation. In later life he repeatedly
      called for a return to minimalist approaches based on the natural menstrual cycle
      to improve oocyte quality over quantity. This article reviews the application of
      ovulation induction to human IVF and celebrates Edwards' abiding impact on the
      field, which firmly grounds him in the reproductive endocrinology pantheon. 

PMID- 24113593
TI  - Emerging combination therapies to overcome resistance in EGFR-driven tumors.
AB  - The epidermal growth factor receptor (EGFR) is responsible for the growth and
      progression of tumor cells; its overexpression and deregulation of its downstream
      signaling pathway have been found in many different neoplasms. These
      characteristics make it an ideal target for cancer treatment. Two classes of EGFR
      inhibitors, which bind to different parts of this molecule, have been developed
      and studied: monoclonal antibodies, such as cetuximab and panitumumab and
      tyrosine kinase inhibitors, including erlotinib and gefitinib. The effectiveness
      of these new drugs is considerably reduced by a number of mechanisms of
      resistance developed by tumor cells. Hence, there is a clear need for better
      characterization of these processes and finding new therapeutic strategies to
      make the action of these drugs more incisive. Here, we describe some of the
      mechanisms of resistance to EGFR inhibitors and review the main innovations
      attempting to overcome these drawbacks. 

PMID- 24113592
TI  - Thermally targeted p21 peptide enhances bortezomib cytotoxicity in androgen
      independent prostate cancer cell lines.
AB  - Prostate cancer remains one of the most common malignancies in men. Besides
      surgical resection, treatments for prostate cancer include hormone therapy,
      chemotherapy, and radiation therapy. Advancement of prostate cancer to an
      androgen-independent state limits the potential of conventional therapeutic
      approaches. Bortezomib, an FDA-approved proteosomal inhibitor for the treatment
      of myeloid leukemia, has been shown to have a positive effect on the inhibition
      of prostate cancer growth. Unfortunately, bortezomib has a very narrow
      therapeutic window, which can lead to severe side effects. Elastin-like
      polypeptide (ELP) is a genetically engineered, thermally responsive
      macromolecular carrier that enables a targeted delivery of the bound molecule
      because of its soluble property under normal physiologic conditions. In addition,
      ELP aggregates in response to mild hyperthermia. Using ELP as a carrier, it is
      possible to improve the pharmacological properties of the therapeutic drug as
      well as reduce toxicity in normal tissues. In this work, we have investigated the
      combination treatment of androgen-independent prostate cancer cells with
      bortezomib and the C-terminal part of the p21(WAF1/CIP1) protein bound to the ELP
      carrier. We have found that combination treatment with bortezomib and ELP-bound
      p21(WAF1/CIP1) protein leads to increased cell cycle arrest as well as apoptosis
      with respect to single treatments. We believe that this approach represents a
      promising direction for the treatment of androgen-independent prostate cancer.

PMID- 24113594
TI  - Multiagent chemotherapy for metastatic adenocarcinoma of the seminal vesicle.
AB  - Adenocarcinoma of the seminal vesicle is a rare condition, with fewer than 60
      cases described in the literature. Most reports highlight the histopathological
      characteristics of the tumor; however, the role of chemotherapy, especially in
      the metastatic setting, is poorly described. In this paper, we describe a patient
      with metastatic disease, who sustained a response to modified FOLFOX6 as first
      line therapy. This platinum-based combination therapy seems effective in this
      scenario and may provide an opportunity for extended survival and relief of
      symptoms. 

PMID- 24113595
TI  - Sustained improvement in hand hygiene adherence: utilizing shared accountability
      and financial incentives.
AB  - OBJECTIVE: To evaluate the impact of an institutional hand hygiene accountability
      program on healthcare personnel hand hygiene adherence. DESIGN: Time-series
      design with correlation analysis. SETTING: Tertiary care academic medical center,
      including outpatient clinics and procedural areas. PARTICIPANTS: Medical center
      healthcare personnel. METHODS: A comprehensive hand hygiene initiative was
      implemented in 2 major phases starting in July 2009. Key facets of the initiative
      included extensive project planning, leadership buy-in and goal setting,
      financial incentives linked to performance, and use of a system-wide shared
      accountability model. Adherence was measured by designated hand hygiene
      observers. Adherence rates were compared between baseline and implementation
      phases, and monthly hand hygiene adherence rates were correlated with monthly
      rates of device-associated infection. RESULTS: A total of 109,988 observations
      were completed during the study period, with a sustained increase in hand hygiene
      adherence throughout each implementation phase (P < .001) as well as from one
      phase to the next (P < .001), such that adherence greater than 85% has been
      achieved since January 2011. Medical center departments were able to reclaim some
      rebate dollars allocated through a self-insurance trust, but during the study
      period, departments did not achieve full reimbursement. Hand hygiene adherence
      rates were inversely correlated with device-associated standardized infection
      ratios (R(@) = 0.70). CONCLUSIONS: Implementation of this multifaceted,
      observational hand hygiene program was associated with sustained improvement in
      hand hygiene adherence. The principles of this program could be applied to other
      medical centers pursuing improved hand hygiene adherence among healthcare
      personnel.

PMID- 24113596
TI  - Hand hygiene behavior: translating behavioral research into infection control
      practice.
AB  - BACKGROUND: In 2009, the World Health Organization (WHO) recommended "My Five
      Moments for Hand Hygiene" (5MHH) to optimize hand hygiene (HH). Uptake of these
      recommendations by healthcare workers (HCWs) remains uncertain. METHODS: We
      prospectively observed HCW compliance to 5 MHH. After observations, eligible HCWs
      who consented to interviews completed surveys on factors associated with HH
      compliance based on constructs from the transtheoretical model of behavioral
      change (TTM) and the theory of planned behavior (TPB). Survey results were
      compared with observed HCW behaviors. RESULTS: There were 968 observations among
      123 HCWs, of whom 110 (89.4%) were female and 63 (51.3%) were nurses. The mean HH
      compliance for all 5 MHH was 23.2% (95% confidence interval [CI], 18.1%-28.3%) by
      direct observation versus 82.4% (95% CI, 79.9%-84.9%) by self report. The HCW 5
      MHH compliance was associated with critical care unit encounters (P < .05),
      medicine unit encounters (P - 0.08, P < .001]), immunocompromised patient
      encounters (P < .05), and HCW prioritized patient advocacy (P < .001). Self
      reported TTM stages of action or maintenance (P < .08) and the total TPB behavior
      score correlated with observed 5 MHH (r = 0.21, P < .02) and with self-reported 5
      MHH compliance (r = 0.53, P < .001). CONCLUSION: Observed HCW compliance to 5 MHH
      was associated with the type of hospital unit, type of provider-patient
      encounter, and theory-based behavioral measures of 5 MHH commitment.

PMID- 24113597
TI  - Factors associated with hand hygiene compliance at a tertiary care teaching
      hospital.
AB  - OBJECTIVE: To identify factors associated with hand hygiene compliance during a
      multiyear period of intervention. DESIGN: Observational study. SETTING: A 719-bed
      tertiary care teaching hospital. PARTICIPANTS: Nursing, physician, technical, and
      support staff. METHODS: Light-duty staff performed hand hygiene observations
      during the period July 2008-December 2012. Infection control implemented hospital
      wide hand hygiene initiatives, including education modules; posters and table
      tents; feedback to units, medical directors and the executive board; and an
      increased number of automated alcohol hand hygiene product dispensers. RESULTS:
      There were 161,526 unique observations; overall compliance was 83%. Significant
      differences in compliance were observed between physician staff (78%) and support
      staff (69%) compared with nursing staff (84%). Pediatric units (84%) and
      intensive care units (84%) had higher compliance than did medical (82%) and
      surgical units (81%). These findings persisted in the controlled multivariate
      model for noncompliance. Additional factors found to be significant in the model
      included greater compliance when healthcare workers were leaving patient rooms,
      when the patient was under contact precautions, and during the evening shift. The
      overall rate of compliance increased from 60% in the first year of observation to
      a peak of 96% in the fourth year, and it decreased to 89% in the final year, with
      significant improvements occurring in each of the 4 professional categories.
      CONCLUSIONS: A multipronged hand hygiene initiative is effective in increasing
      compliance rates among all categories of hospital workers. We identified a
      variety of factors associated with increased compliance. Additionally, we note
      the importance of continuous interventions in maintaining high compliance rates.

PMID- 24113598
TI  - Bacteremia and mortality with urinary catheter-associated bacteriuria.
AB  - OBJECTIVE: Although catheter-associated urinary tract infection (CAUTI) and
      catheter-associated asymptomatic bacteriuria (CAABU) are clinically distinct
      conditions, most literature describing the risks of bacteriuria does not
      distinguish between them. We studied the relationship between catheter-associated
      bacteriuria and bacteremia from a urinary source in CAUTI relative to that in
      CAABU. Second, we investigated whether the presence or absence of urinary
      symptoms in catheterized patients with bacteriuria was associated with bacteremia
      from any source or mortality. Finally, we explored the effect of antimicrobial
      treatment of bacteriuria on subsequent bacteremia from any source and mortality.
      DESIGN: We performed a retrospective cohort study with 30 days of follow-up after
      an initial positive urine culture. CAUTI and CAABU were defined by Infectious
      Diseases Society of America guidelines. SETTING: A large tertiary care facility.
      PATIENTS: All inpatients with a urinary catheter (external or indwelling) and a
      positive urine culture between October 2010 and June 2011. RESULTS: We captured
      444 episodes of catheter-associated bacteriuria in 308 patients; 128 (41.6%)
      patients had CAUTI, and 180 (58.4%) had CAABU. Three episodes of bacteriuria were
      followed by bacteremia from a urinary source (0.7%). CAUTI, rather than CAABU,
      was associated with bacteremia from any source, but neither CAUTI nor CAABU
      predicted subsequent mortality. Use of antimicrobial agents to treat bacteriuria
      was not associated with either bacteremia from any source or mortality.
      CONCLUSIONS: Bacteremia from a urinary source was infrequent, and there was no
      evidence of an association of mortality with symptomatic versus asymptomatic
      bacteriuria in this population. Antibiotic treatment of bacteriuria did not
      affect outcomes.

PMID- 24113599
TI  - The effect of a hospital-wide urine culture screening intervention on the
      incidence of extended-spectrum beta-lactamase-producing Escherichia coli and
      Klebsiella species.
AB  - OBJECTIVE: Optimal strategies for limiting the transmission of extended-spectrum
      beta-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the
      hospital setting remain unclear. The objective of this study was to evaluate the
      impact of a urine culture screening strategy on the incidence of ESBL-EK. DESIGN:
      Prospective quasi-experimental study. SETTING: Two intervention hospitals and one
      control hospital within a university health system from 2005 to 2009. PATIENTS
      AND INTERVENTION: All clinical urine cultures with E. coli or Klebsiella spp were
      screened for ESBL-EK. Patients determined to be colonized or infected with ESBL
      EK were placed in a private room with contact precautions. The primary outcome of
      interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases
      occurring more than 48 hours after admission). Changes in monthly ESBL-EK
      incidence rates were evaluated with mixed-effects Poisson regression models, with
      adjustment for institution-level characteristics (eg, total admissions). RESULTS:
      The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to
      2.16/10,000 patient-days during the study period. The incidence of community
      acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to
      0.92/10,000 patient-days (P < .001). On multivariable analysis, the intervention
      was not significantly associated with a reduction in nosocomial ESBL-EK incidence
      (incidence rate ratio, 1.38 [95% confidence interval, 0.83-2.31]; P - .21).
      CONCLUSIONS: Universal screening of clinical urine cultures for ESBL-EK did not
      result in a reduction in nosocomial ESBL-EK incidence rates, most likely because
      of increases in importation of ESBL-EK cases from the community. Further studies
      are needed on elucidating optimal infection control interventions to limit spread
      of ESBL-producing organisms in the hospital setting.

PMID- 24113600
TI  - Central line-associated bloodstream infection in neonatal intensive care units.
AB  - OBJECTIVE: Describe the epidemiology of central line-associated bloodstream
      infections (CLABSIs) in neonatal intensive care units (NICUs) participating in a
      standardized and mandatory CLABSI surveillance program. DESIGN: Retrospective
      cohort. Setting. We included patients admitted (April 2007-March 2011) to 7 level
      II/III NICUs who developed a CLABSI (as defined by the National Healthcare Safety
      Network). METHODS: CLABSIs/1,000 central line-days and device utilization ratio
      were calculated; chi(2) test, Student t test, Kruskal-Wallis, and Poisson
      regression were used. RESULTS: Overall, 191 patients had 202 CLABSI episodes for
      a pooled mean rate of 4.0 CLABSIs/1,000 central line-days and a device
      utilization ratio of 0.20. Annual pooled mean CLABSI rates increased from 3.6 in
      2007-2008 to 5.1 CLABSIs/1,000 central line-days in 2010-2011 (P - .01). The all
      cause 30-day case fatality proportion was 8.9% (n = 17) and occurred a median of
      8 days after CLABSI. Coagulase-negative Staphylococcus was identified in 112
      (50.5%) cases. Staphylococcus aureus was identified in 22 cases, and 3 (13.6%)
      were resistant to methicillin. An underlying intra-abdominal pathology was found
      in 20% (40/202) of CLABSI cases, 50% of which were reported in the last year of
      study. When adjusted for mean birth weight, annual CLABSI incidence rates were
      independently associated with the proportion of intra-abdominal pathology (P =
      .007) and the proportion of pulmonary pathology (P = .016) reported. CONCLUSION:
      The increase in CLABSI rates in Quebec NICUs seems to be associated with an
      increased proportion of cases with underlying intra-abdominal and pulmonary
      pathologies, which needs further investigation.

PMID- 24113601
TI  - Comparison of visual versus microscopic methods to detect blood splatter from an
      intravascular catheter with engineered sharps injury protection.
AB  - OBJECTIVE: To determine whether retractable intravenous devices produced blood
      splatter and whether blood splatter frequency differed between visual and
      microscopy detection methods. METHODS: In this laboratory-based experiment, 105
      venipunctures were performed in a simulated brachial vein containing mock venous
      blood. The retraction mechanism was activated in a testing chamber with precut
      fabric filters, placed at 3 different locations, to capture blood splatter.
      Differences in filter mass, visual inspection, and microscopic analysis for
      presence of blood on filters were the units of analysis. Descriptive statistics,
      paired Student t tests, and kappa statistics were used for data analysis.
      RESULTS: Blood splatter was detected visually and microscopically as follows:
      filter A, 70% and 71%, respectively; filter B, 12% and 9%, respectively; and
      filter C, 13% and 10%, respectively. A statistically significant difference was
      observed in the mean mass of filter A between before and after activation when
      confirmed by the naked eye (P = .014) and microscopically (P = .0092).
      Substantial agreement between methods was observed for filter A (kappa - 0.78
      [95% confidence interval, 0.64-0.92]), filter B (kappa - 0.73 [95% confidence
      interval, 0.51-0.95]), and filter C (kappa - 0.75 [95% confidence interval, 0.55
      0.96]). However, blood was detected by microscopy and not by the naked eye in 7
      instances (7%). CONCLUSIONS: Our findings demonstrate that splatter, which can
      potentially expose healthcare workers (HCWs) to bloodborne pathogens, is
      associated with the activation of intravascular catheters with retraction
      mechanisms. HCWs may not detect this splatter when it occurs and may not report a
      splash to mucous membranes or nonintact skin. The need to wear personal
      protective equipment when using such devices is reinforced.

PMID- 24113602
TI  - Mathematical modeling of pathogen trajectory in a patient care environment.
AB  - OBJECTIVE: Minimizing healthcare worker exposure to airborne infectious pathogens
      is an important infection control practice. This study utilized mathematical
      modeling to evaluate the trajectories and subsequent concentrations of particles
      following a simulated release in a patient care room. DESIGN: Observational
      study. SETTING: Biocontainment unit patient care room at a university-affiliated
      tertiary care medical center. METHODS: Quantitative mathematical modeling of
      airflow in a patient care room was achieved using a computational fluid dynamics
      software package. Models were created on the basis of a release of particles from
      various locations in the room. Computerized particle trajectories were presented
      in time-lapse fashion over a blueprint of the room. A series of smoke tests were
      conducted to visually validate the model. RESULTS: Most particles released from
      the head of the bed initially rose to the ceiling and then spread across the
      ceiling and throughout the room. The highest particle concentrations were
      observed at the head of the bed nearest to the air return vent, and the lowest
      concentrations were observed at the foot of the bed. CONCLUSIONS: Mathematical
      modeling provides clinically relevant data on the potential exposure risk in
      patient care rooms and is applicable in multiple healthcare delivery settings.
      The information obtained through mathematical modeling could potentially serve as
      an infection control modality to enhance the protection of healthcare workers.

PMID- 24113603
TI  - Improving stethoscope disinfection at a children's hospital.
AB  - OBJECTIVE: Stethoscopes are contaminated with pathogenic bacteria and pose a risk
      for transmission of infections, but few clinicians disinfect their stethoscope
      after every use. We sought to improve stethoscope disinfection rates among
      pediatric healthcare providers by providing access to disinfection materials and
      visual reminders to disinfect stethoscopes. DESIGN: Prospective intervention
      study. SETTING: Inpatient units and emergency department of a major pediatric
      hospital. PARTICIPANTS: Physicians and nurses with high anticipated stethoscope
      use. METHODS: Baskets filled with alcohol prep pads and a sticker reminding
      providers to regularly disinfect stethoscopes were installed outside of patient
      rooms. Healthcare providers' stethoscope disinfection behaviors were directly
      observed before and after the intervention. Multivariable logistic regression
      models were created to identify independent predictors of stethoscope
      disinfection. RESULTS: Two hundred twenty-six observations were made in the
      preintervention period and 261 in the postintervention period (83% were of
      physicians). Stethoscope disinfection compliance increased significantly from a
      baseline of 34% to 59% postintervention (P < .001). In adjusted analyses, the
      postintervention period was associated with improved disinfection among both
      physicians (odds ratio [OR], 2.3 [95% confidence interval (CI), 1.4-3.5]) and
      nurses (OR, 14.3 [95% CI, 4.6-44.6]). Additional factors independently associated
      with disinfection included subspecialty unit (vs general pediatrics; OR, 0.5 [95%
      CI, 0.3-0.8]) and contact precautions (OR, 2.3 [95% CI, 1.2-4.1]). CONCLUSIONS:
      Providing stethoscope disinfection supplies and visible reminders outside of
      patient rooms significantly increased stethoscope disinfection rates among
      physicians and nurses at a children's hospital. This simple intervention could be
      replicated at other healthcare facilities. Future research should assess the
      impact on patient infections.

PMID- 24113604
TI  - A successful strategy for increasing the influenza vaccination rate of healthcare
      workers without a mandatory policy outside of the United States: a multifaceted
      intervention in a Japanese tertiary care center.
AB  - OBJECTIVE: Although mandatory vaccination programs have been effective in
      improving the vaccination rate among healthcare workers, implementing this type
      of program can be challenging because of varied reasons for vaccine refusal. The
      purpose of our study is to measure improvement in the influenza vaccination rate
      from a multifaceted intervention at a Japanese tertiary care center where
      implementing a mandatory vaccination program is difficult. DESIGN: Before-and
      after trial. PARTICIPANTS AND SETTING: Healthcare workers at a 550-bed, tertiary
      care, academic medical center in Sapporo, Japan. INTERVENTIONS: We performed a
      multifaceted intervention including (1) use of a declination form, (2) free
      vaccination, (3) hospital-wide announcements during the vaccination period, (4)
      prospective audit and real-time telephone interview for healthcare workers who
      did not receive the vaccine, (5) medical interview with the hospital executive
      for noncompliant (no vaccine, no declination form) healthcare workers during the
      vaccination period, and (6) mandatory submission of a vaccination document if
      vaccinated outside of the study institution. RESULTS: With the new multifaceted
      intervention, the vaccination rate in the 2012-2013 season increased
      substantially, up to 97%. This rate is similar to that reported in studies with a
      mandatory vaccination program. Improved vaccination acceptance, particularly
      among physicians, likely contributed to the overall increase in the vaccination
      rate reported in the study. CONCLUSIONS: Implementation of comprehensive
      strategies with strong leadership can lead to substantial improvements in vaccine
      uptake among healthcare workers even without a mandatory vaccination policy. The
      concept is especially important for institutions where implementing mandatory
      vaccination programs is challenging.

PMID- 24113605
TI  - Public reporting of healthcare-associated infections: epidemiologists'
      perspectives.
AB  - Public reporting of healthcare-associated infections is pervasive, with 33 states
      and the District of Columbia mandating public disclosure. We surveyed hospital
      epidemiologists on the perceived value of state public reports. Respondents
      believed consumers are unaware and do not consider the information important, but
      they indicated that epidemiologists have a role in consumer education. 

PMID- 24113606
TI  - Inappropriate testing for urinary tract infection in hospitalized patients: an
      opportunity for improvement.
AB  - Urine cultures are frequently obtained for hospitalized patients. We reviewed
      documented indications for culture and compared these with professional society
      guidelines. Lack of documentation and important clinical scenarios (before
      orthopedic procedures and when the patient has altered mental status without a
      urinary catheter) are highlighted as areas of use outside of current guidelines. 

PMID- 24113607
TI  - Beyond the bundle: a survey of central line-associated bloodstream infection
      prevention practices used in US and Canadian pediatric hospitals.
AB  - We surveyed US and Canadian pediatric hospitals about their use of central line
      associated bloodstream infection (CLABSI) prevention strategies beyond typical
      insertion and maintenance bundles. We found wide variation in supplemental
      strategies across hospitals and in their penetration within hospitals. Future
      studies should assess specific adjunctive prevention strategies and CLABSI rates.

PMID- 24113608
TI  - Baseline measure of alcohol-based skin preparation agents before 2011 National
      Quality Forum recommendation in a general surgery population.
AB  - The National Quality Forum (2011) recommends the use of alcohol-based skin
      preparation agents before surgery to help prevent infections. This multihospital
      study (n = 3,794) evaluates its use in a general surgery patient population
      before the National Quality Forum recommendation. Forty-seven percent of cases
      received an alcohol-based skin preparation agent.

PMID- 24113609
TI  - Outbreak of joint infections associated with magnetic resonance arthrograms
      performed at an outpatient radiology center.
AB  - An outbreak of methicillin-susceptible Staphylococcus aureus joint infections
      occurred at an outpatient radiology center. We identified 7 case patients; all
      had undergone magnetic resonance arthrograms with intra-articular joint
      injections. The outbreak was likely due to unsafe injection practices in
      preparation of contrast solution for intra-articular injection. 

PMID- 24113610
TI  - Estimated burden of methicillin-resistant Staphylococcus aureus in California
      hospitals after changes to administrative codes, 2005-2010.
AB  - We assess the impact of revised International Classification of Diseases, Ninth
      Revision, codes on methicillin-resistant Staphylococcus aureus burden in
      California hospitals. Codes were rapidly adopted, demonstrating new capture of
      colonization and continued relatively stable capture of infections. Nevertheless,
      despite new colonization codes, coded data demonstrated poor retention between
      serial hospitalizations. 

PMID- 24113611
TI  - A Clostridium difficile infection (CDI) stewardship initiative improves adherence
      to practice guidelines for management of CDI.
AB  - A Clostridium difficile infection (CDI) stewardship initiative reduced
      inappropriate prescription of empirical CDI therapy and improved timeliness of
      treatment and adherence to clinical practice guidelines for management of CDI.
      The initiative required minimal resources and could easily be incorporated into
      traditional antimicrobial stewardship programs. 

PMID- 24113612
TI  - Laboratory-confirmed influenza B infection in immunized long-term care facility
      residents receiving oseltamivir prophylaxis in Ontario.
AB  - We report on an influenza B outbreak in an Ontario long-term care facility in
      which 2 immunized residents receiving oseltamivir prophylaxis for at least 5 days
      developed laboratory-confirmed influenza B infection. All isolates were tested
      for the most common oseltamivir resistance, and none of them had resistance
      identified. 

PMID- 24113613
TI  - Assessing the relative burden of hospital-acquired infections in a network of
      community hospitals.

PMID- 24113614
TI  - Efficacy of dilute hypochlorite solutions and an electrochemically activated
      saline solution containing hypochlorous acid for disinfection of methicillin
      resistant Staphylococcus aureus in a pig skin model.

PMID- 24113615
TI  - Effective hospital waste classification to overcome occupational health issues
      and reduce waste disposal cost.

PMID- 24113616
TI  - Associations between carbapenem use, carbapenem-resistant Pseudomonas aeruginosa,
      and carbapenem-resistant Acinetobacter baumannii.

PMID- 24113618
TI  - Estimation of mouth level exposure to smoke constituents of cigarettes with
      different tar levels using filter analysis.
AB  - A nicotine part-filter method can be applied to estimate smokers' mouth level
      exposure (MLE) to smoke constituents. The objectives of this study were (1) to
      generate calibration curves for 47 smoke constituents, (2) to estimate MLE to
      selected smoke constituents using Japanese smokers of commercially available
      cigarettes covering a wide range of International Organization for
      Standardization tar yields (1-21mg/cigarette), and (3) to investigate
      relationships between MLE estimates and various machine-smoking yields. Five
      cigarette brands were machine-smoked under 7 different smoking regimes and smoke
      constituents and nicotine content in part-filters were measured. Calibration
      curves were then generated. Spent cigarette filters were collected from a target
      of 50 smokers for each of the 15 brands and a total of 780 filters were obtained.
      Nicotine content in part-filters was then measured and MLE to each smoke
      constituent was estimated. Strong correlations were identified between nicotine
      content in part-filters and 41 out of the 47 smoke constituent yields. Estimates
      of MLE to acetaldehyde, acrolein, 1,3-butadiene, benzene, benzo[a]pyrene, carbon
      monoxide, and tar showed significant negative correlations with corresponding
      constituent yields per mg nicotine under the Health Canada Intense smoking
      regime, whereas significant positive correlations were observed for N
      nitrosonornicotine and (4-methylnitrosoamino)-1-(3-pyridyl)-1-butanone.

PMID- 24113619
TI  - Multidisciplinary one-stage risk-reducing gynaecological and breast surgery with
      immediate reconstruction in BRCA-gene carrier women.
AB  - Familial breast cancer accounts for 5-10% of all breast cancers. Due to BRCA1/2
      tumour suppressor gene mutation, hereditary breast and ovarian syndrome is the
      most common form. Risk-reducing gynaecological and breast surgery is offered to
      such patients in ever-increasing numbers. Hence, the development of a multi
      specialty combined treatment approach is called for. Twenty-two BRCA gene
      mutation carrier women underwent one-stage gynaecological and breast risk
      reducing surgery and immediate reconstruction between January 2005 and December
      2011 at the Belfast City Hospital. Their mean age was 41.2 years (median 41
      years). Nearly half of the patients were BRCA2 and a quarter were BRCA1 carriers.
      The rest were positive for both genes. Hormone-replacement therapy was initiated
      in 14 women. Average theatre time and stay in the hospital were three hours and
      two and a half days, respectively. Two patients developed complications unrelated
      to combining the procedures. Both were treated conservatively and recovered. The
      one-stage approach logically proves economical by limiting the time the patients
      are in the hospital and away from work. We describe our multidisciplinary team
      service that is offering safe and economical one-stage risk-reducing surgery and
      reconstruction to young BRCA gene-mutation carrier women in Northern Ireland. 

PMID- 24113620
TI  - Diabetes mellitus without metformin intake is associated with worse oncologic
      outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.
AB  - AIMS: Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer
      incidence and outcomes. To date, the effect of DM and its treatment on prognosis
      in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the
      hypothesis that DM and metformin use impact oncologic outcomes of patients
      treated with radical nephroureterectomy (RNU) for UTUC. METHODS: Retrospective
      analysis of 2492 patients with UTUC treated at 23 institutions with RNU without
      neoadjuvant therapy. Cox regression models addressed the association of DM and
      metformin use with disease recurrence, cancer-specific mortality and any-cause
      mortality. RESULTS: A total of 365 (14.3%) patients had DM and 194 (7.8%)
      patients used metformin. Within a median follow-up of 36 months, 663 (26.6%)
      patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and
      884 (35.5%) patients died from any cause. Diabetic patients who did not use
      metformin were at significantly higher risk of disease recurrence and cancer
      specific death compared to non-diabetic patients and diabetic patients who used
      metformin. In multivariable Cox regression analyses, DM treated without metformin
      was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p
      = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008).
      CONCLUSIONS: Diabetic UTUC patients without metformin use have significantly
      worse oncologic outcomes than diabetics who used metformin and non-diabetics. The
      possible mechanism behind the impact of DM on UTUC biology and the potentially
      protective effect of metformin need further elucidation.

PMID- 24113621
TI  - Selective axillary dissection after axillary reverse mapping to prevent breast
      cancer-related lymphoedema.
AB  - BACKGROUND: It has recently been reported that, using axillary reverse mapping
      (ARM), the lymphatics from the arm can be spared to reduce the incidence of
      breast-cancer-related lymphoedema (BCRL). The aim of this study was to assess the
      feasibility of selective axillary dissection (SAD) after using ARM and partially
      preserving arm drainage, and to assess the occurrence of BCRL. METHODS: Using a
      radioisotope and lymphoscintigraphy, ARM was performed in 60 patients scheduled
      for SAD, who were subsequently divided for the purpose of comparing the BCRL
      rates into: group A, comprising 45 patients who successfully underwent SAD with a
      residual lymphatic hot spot; and group B with 15 whose hot nodes were removed as
      is normally the case during complete axillary lymph node dissection (ALND).
      RESULTS: SAD was feasible in 75% of the 60 patients. SAD was completed
      successfully in 19 of the first 30 patients, and in 26 of the second 30 patients
      (p = 0.072). The median follow-up was 16 months (6-36), during which 9 patients
      developed a BCRL, 4 in group A (9%) and 5 in group B (33%); p = 0.035. None of
      the patients had nodal relapses during the follow-up. CONCLUSIONS: Using a
      radioisotope enables an effective and safe SAD in a large proportion of patients.
      There was evidence of a trend to suggest a learning curve. The rate of BCRL after
      SAD was less than one third of the rate recorded after ALND, a result that should
      encourage the development of the former technique.

PMID- 24113622
TI  - Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient
      mice.
AB  - Despite the established role of alveolar type II epithelial cells for the
      maintenance of pulmonary function, little is known about the deregulation of
      lipid composition in the pathogenesis of pulmonary fibrosis. The elongation of
      long-chain fatty acids family member 6 (Elovl6) is a rate-limiting enzyme
      catalysing the elongation of saturated and monounsaturated fatty acids. Here we
      show that Elovl6 expression is significantly downregulated after an intratracheal
      instillation of bleomycin (BLM) and in human lung with idiopathic pulmonary
      fibrosis. Elovl6-deficient (Elovl6-/-) mice treated with BLM exhibit severe
      fibroproliferative response and derangement of fatty acid profile compared with
      wild-type mice. Furthermore, Elovl6 knockdown induces a change in fatty acid
      composition similar to that in Elovl6-/- mice, resulting in induction of
      apoptosis, TGF-beta1 expression and reactive oxygen species generation. Our
      findings demonstrate a previously unappreciated role for Elovl6 in the regulation
      of lung homeostasis, and in pathogenesis and exacerbation of BLM-induced
      pulmonary fibrosis.

PMID- 24113623
TI  - What has been achieved in HIV prevention, treatment and care for people who
      inject drugs, 2010-2012? A review of the six highest burden countries.
AB  - OBJECTIVE: In 2010 the international HIV/AIDS community called on countries to
      take action to prevent HIV transmission among people who inject drugs (PWID). To
      set a baseline we proposed an "accountability matrix", focusing upon six
      countries accounting for half of the global population of PWID: China, Malaysia,
      Russia, Ukraine, Vietnam and the USA. Two years on, we review progress. DESIGN:
      We searched peer-reviewed literature, conducted online searches, and contacted
      experts for 'grey' literature. We limited searches to documents published since
      December 2009 and used decision rules endorsed in earlier reviews. RESULTS:
      Policy shifts are increasing coverage of key interventions for PWID in China,
      Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral
      treatment (ART) and opioid substitution treatment (OST) in both Vietnam and
      China, and a shift in Malaysia from a punitive law enforcement approach to
      evidence-based treatment are promising developments. The USA and Russia have had
      no advances on PWID access to needle and syringe programmes (NSP), OST or ART.
      There have also been policy setbacks in these countries, with Russia reaffirming
      its stance against OST and closing down access to information on methadone, and
      the USA reinstituting its Congressional ban on Federal funding for NSPs.
      CONCLUSIONS: Prevention of HIV infection and access to HIV treatment for PWID is
      possible. Whether countries with concentrated epidemics among PWID will meet
      goals of achieving universal access and eliminating new HIV infections remains
      unknown. As long as law enforcement responses counter public health responses,
      health-seeking behaviour and health service delivery will be limited.

PMID- 24113624
TI  - It pays to be Herr Kaiser: Germans with noble-sounding surnames more often work
      as managers than as employees.
AB  - In the field study reported here (N = 222,924), we found that Germans with noble
      sounding surnames, such as Kaiser ("emperor"), Konig ("king"), and Furst
      ("prince"), more frequently hold managerial positions than Germans with last
      names that either refer to common everyday occupations, such as Koch ("cook"),
      Bauer ("farmer"), and Becker/Backer ("baker"), or do not refer to any social
      role. This phenomenon occurs despite the fact that noble-sounding surnames never
      indicated that the person actually held a noble title. Because of basic
      properties of associative cognition, the status linked to a name may spill over
      to its bearer and influence his or her occupational outcomes. 

PMID- 24113626
TI  - Cortical surface alignment in multi-subject spatiotemporal independent EEG source
      imaging.
AB  - Brain responses to stimulus presentations may vary widely across subjects in both
      time course and spatial origins. Multi-subject EEG source imaging studies that
      apply Independent Component Analysis (ICA) to data concatenated across subjects
      have overlooked the fact that projections to the scalp sensors from functionally
      equivalent cortical sources vary from subject to subject. This study demonstrates
      an approach to spatiotemporal independent component decomposition and alignment
      that spatially co-registers the MR-derived cortical topographies of individual
      subjects to a well-defined, shared spherical topology (Fischl et al., 1999). Its
      efficacy for identifying functionally equivalent EEG sources in multi-subject
      analysis is demonstrated by analyzing EEG and behavioral data from a stop-signal
      paradigm using two source-imaging approaches, both based on individual subject
      independent source decompositions. The first, two-stage approach uses temporal
      infomax ICA to separate each subject's data into temporally independent
      components (ICs), then estimates the source density distribution of each IC
      process from its scalp map and clusters similar sources across subjects (Makeig
      et al., 2002). The second approach, Electromagnetic Spatiotemporal Independent
      Component Analysis (EMSICA), combines ICA decomposition and source current
      density estimation of the artifact-rejected data into a single spatiotemporal ICA
      decomposition for each subject (Tsai et al., 2006), concurrently identifying both
      the spatial source distribution of each cortical source and its event-related
      dynamics. Applied to the stop-signal task data, both approaches gave IC clusters
      that separately accounted for EEG processes expected in stop-signal tasks,
      including pre/postcentral mu rhythms, anterior-cingulate theta rhythm, and right
      inferior frontal responses, the EMSICA clusters exhibiting more tightly
      correlated source areas and time-frequency features. 

PMID- 24113627
TI  - Antimicrobial peptides isolated from Phyllomedusa nordestina (Amphibia) alter the
      permeability of plasma membrane of Leishmania and Trypanosoma cruzi.
AB  - Nature has provided inspiration for Drug Discovery studies and amphibian
      secretions have been used as a promising source of effective peptides which could
      be explored as novel drug prototypes for neglected parasitic diseases as
      Leishmaniasis and Chagas disease. In this study, we isolated four antimicrobial
      peptides (AMPs) from Phyllomedusa nordestina secretion, and studied their
      effectiveness against Leishmania (L.) infantum and Trypanosoma cruzi. The
      antiparasitic fractions were characterized by mass spectrometry and Edman
      degradation, leading to the identification of dermaseptins 1 and 4 and
      phylloseptins 7 and 8. T. cruzi trypomastigotes were susceptible to peptides,
      showing IC50 values in the range concentration of 0.25-0.68 MUM. Leishmania (L.)
      infantum showed susceptibility to phylloseptin 7, presenting an IC50 value of 10
      MUM. Except for phylloseptin 7 which moderate showed cytotoxicity (IC50=34 MUM),
      the peptides induced no cellular damage to mammalian cells. The lack of
      mitochondrial oxidative activity of parasites detected by the MTT assay,
      suggested that peptides were leishmanicidal and trypanocidal. By using the
      fluorescent probe SYTOX((r)) Green, dermaseptins 1 and 4 and phylloseptins 7 and
      8 showed time-dependent plasma membrane permeabilization of T. cruzi;
      phylloseptin 7 also showed a similar effect in Leishmania parasites. The present
      study demonstrates for the first time that AMPs target the plasma membrane of
      Leishmania and T. cruzi, leading to cellular death. Considering the potential of
      amphibian peptides against protozoan parasites and the reduced mammalian
      toxicity, they may contribute as scaffolds for drug design studies.

PMID- 24113628
TI  - Paliperidone palmitate versus oral risperidone and risperidone long-acting
      injection in patients with recently diagnosed schizophrenia: a tolerability and
      efficacy comparison.
AB  - Early in the course of illness, patients with schizophrenia may be particularly
      susceptible to adverse events (AEs). In this post-hoc, subgroup analysis of a 13
      week, double-blind, double-dummy, multicenter study, patients recently diagnosed
      with schizophrenia (<= 5 years) were administered once-monthly flexible-dose
      paliperidone palmitate (PP) (n=161; initiation doses, 150 mg eq day 1 and 100 mg
      eq day 8) [PP doses can be expressed as milligram equivalents (mg eq) of
      paliperidone or as milligrams (mg) of PP. 150 mg eq paliperidone=234 mg PP; 100
      mg eq paliperidone=156 mg PP. In the USA, dosing tends to be expressed in mg] or
      oral risperidone [during initiation of risperidone long-acting injection (RLAI)
      days 1-28] and biweekly flexible-dose RLAI (n=173; initial injection day 8).
      Assessments were performed at baseline and days 4, 15, 22, 36, 64, and 92.
      Because of RLAI's release profile, data through day 22 correspond to oral
      risperidone in the RLAI arm. During this period, the AE profile and onset of
      efficacy of PP and oral risperidone were similar. The overall AE rates at week 13
      for PP and RLAI were 54.7 and 50.3%, respectively, for any AE; 11.2 and 8.1% for
      extrapyramidal symptom-related AEs; and 2.5 and 2.3% for prolactin-related AEs.
      No significant differences in the mean weight change, most metabolic parameters,
      or mean efficacy measures were observed at end point. In patients with recently
      diagnosed schizophrenia, the tolerability and efficacy of PP and RLAI were
      generally similar over 13 weeks.

PMID- 24113625
TI  - Quantitative magnetic susceptibility mapping without phase unwrapping using
      WASSR.
AB  - The magnetic susceptibility of tissue within and around an image voxel affects
      the magnetic field and thus the local frequency in that voxel. Recently, it has
      been shown that spatial maps of frequency can be used to quantify local
      susceptibility if the contributions of surrounding tissue can be deconvolved.
      Currently, such quantitative susceptibility mapping (QSM) methods employ gradient
      recalled echo (GRE) imaging to measure spatial differences in the signal phase
      evolution as a function of echo time, from which frequencies can be deduced.
      Analysis of these phase images, however, is complicated by phase wraps, despite
      the availability and usage of various phase unwrapping algorithms. In addition,
      lengthy high-resolution GRE scanning often heats the magnet bore, causing the
      magnetic field to drift over several Hertz, which is on the order of the
      frequency differences between tissues. Here, we explore the feasibility of
      applying the WAter Saturation Shift Referencing (WASSR) method for 3D whole brain
      susceptibility imaging. WASSR uses direct saturation of water protons as a
      function of frequency irradiation offset to generate frequency maps without phase
      wraps, which can be combined with any image or spectroscopy acquisition. By
      utilizing a series of fast short-echo-time direct saturation images with multiple
      radiofrequency offsets, a frequency correction for field drift can be applied
      based on the individual image phases. Regions of interest were delineated with an
      automated atlas-based method, and the average magnetic susceptibilities
      calculated from frequency maps obtained from WASSR correlated well with those
      from the phase-based multi-echo GRE approach at 3T. 

PMID- 24113629
TI  - Pragmatic diabetes management in nursing homes: individual care plan.
AB  - Although the management of diabetes as a simple entity has been extensively
      developed, there is a dearth of evidence in elderly, frail patients with multiple
      comorbidities and polymedication. This population represents a large proportion
      of the residents of nursing homes (NHs). As a multidisciplinary group of French
      experts (geriatricians, endocrinologists, diabetologists, and general
      practitioners) with practical experience in this area, which is growing in
      magnitude throughout the world, we convened to compile pragmatic, simple advice
      on the management of elderly, frail diabetic patients. Given demands on NH
      personnel (manager, medical coordinator, nurses, and, at the front line of care
      provision, the undertrained and overworked carers), coupled with the
      quasiconstant of high staff turnover, the foundation stone of a patient's
      diabetes management is an Individual Care Plan (ICP) expressed in layman's
      language. This document that is opened on the patient's admission aims to make
      sure that the prescriptions established at admission are followed, notably to
      ensure correct treatment and adapted, regular monitoring with dates and times
      when examinations and tests are due. This includes monitoring of the diabetes
      control (HbA1c and, if necessary, blood and urine glucose) and its complications
      (cardiovascular disease, hypoglycemia, ocular problems, foot disorders,
      malnutrition, peripheral neuropathy, kidney failure). A necessary corollary is
      the training of staff to understand the specificities of caring for a frail
      patient with diabetes, on what to do in a potential emergency, and how to keep
      the ICP up to date for consultation by doctors and nurses. 

PMID- 24113630
TI  - Making delirium prevention acceptable in nursing homes.

PMID- 24113631
TI  - Standard business practice has been around in academia.

PMID- 24113632
TI  - Strategic continuity planning: the first critical step.
AB  - Many companies (and business continuity professionals) believe a company needs a
      comprehensive, all-inclusive business continuity plan. Often they reach this
      conclusion after other companies or potential clients have requested to see their
      business continuity plan as a precondition of doing business. Companies without
      'a plan' are then tempted to go out and hire a business continuity person and
      tell them to 'Create a plan!' This makes perfect sense to the executive team, but
      this approach will probably not work in a real event. This paper addresses the
      shortcomings of producing tactical documentation and calling it 'The Plan', and
      discusses ways to engage management in the development of a corporate strategy to
      be used during and after an event. 

PMID- 24113633
TI  - Digital detectives and virtual volunteers: Integrating emergent online
      communities into disaster response operations.
AB  - The demonstration of altruistic behaviours by disaster survivors, and even those
      observing emergencies from afar, is well documented. Over the past few decades,
      government-sponsored crisis planning has evolved to include affiliated volunteer
      agencies, with a general acknowledgment of the need to plan for unaffiliated or
      spontaneous volunteers. Just as the understanding of the need for volunteers has
      grown, so too have the ways in which volunteers are able to donate their time and
      skills. The popularity of social media networks and online communities provide
      new ways for the public to get involved in disaster response. Public service
      agencies should be proactive in investigating these emerging platforms and
      understanding their impacts during crises. Established methods of integrating on
      scene volunteers into post-disaster response operations can be used as templates
      for creating virtual volunteer programmes. 

PMID- 24113634
TI  - Identifying single points of failure in your organisation.
AB  - Single points of failure may spell disaster for businesses that have not
      adequately identified and mitigated these critical risks. A single point of
      failure audit will identify the single points of failure in all functional areas
      that may negatively impact organisational processes and process flows. This paper
      provides a holistic approach to constructing a successful single point of failure
      audit and identifies the systems that are frequently the sources of single points
      of failure. It also examines the internal and external risks that may spawn
      single points of failure and provides various mitigation strategies for the
      systems identified. 

PMID- 24113635
TI  - National mass care strategy: a national integrated approach.
AB  - Mass care refers to a wide range of humanitarian activities that collectively
      provide life- sustaining services, such as emergency sheltering, feeding,
      reunification, distribution of emergency supplies and recovery information,
      before or in the aftermath of an emergency or disaster. Most services are
      coordinated and provided by non-governmental organisations and/or local
      government. Based on the lessons learned in the aftermath of Hurricanes Katrina
      and Rita in 2005, the American Red Cross, the Federal Emergency Management Agency
      and the National Voluntary Organizations Active in Disasters joined efforts to
      expand national mass care capabilities in order to support survivors in the wake
      of catastrophic events, as well as to enhance the integration of volunteers and
      non-governmental organisations into the broader national effort. These efforts
      resulted in the creation of the National Mass Care Council in 2010, with
      representatives of Federal and State agencies, voluntary organisations and the
      private sector working together to develop a unified approach to mass care and to
      ensure the provision of consistent and uniform services across the USA,
      regardless of the magnitude of the event. 

PMID- 24113636
TI  - A winning combination: the 3Cs of business continuity.
AB  - Contingency planning is a natural part of business life and is used across
      identified strategic, financial and operational risks. But is it being done well
      and is it the right approach all of the time? This paper shows how contingency
      planning forms one layer of a three-line defence termed 'the 3Cs of business
      continuity': contingency planning; continuity capability; crisis response.
      Collectively, 'the 3Cs' help organisations deliver a robust response to the risks
      that can be seen and those that cannot. 

PMID- 24113637
TI  - 'Plans are useless'.
AB  - An essential element in crisis recovery is the protection and/or recovery of
      reputation. This calls for a crisis communications function that is of more than
      passing interest to the business continuity specialist and which presents two
      major challenges in this era of process-driven management: (1) it is an inexact
      science, more about common sense, psychology, empathy and 'playing it by ear'
      than about box ticking; (2) it does not lend itself to detailed, rigid plans,
      although some degree of planning is essential. This paper outlines a flexible
      approach that will help the crisis team to develop a workable communications plan
      that strikes a balance between being too detailed and too sketchy. It argues that
      the whole management team should be involved in developing the plan and sets a
      number of questions, which, on being answered, will help a realistic, achievable
      and effective plan to evolve. 

PMID- 24113638
TI  - Improving decision making in crisis.
AB  - The most critical activity during emergencies or crises is making decisions about
      what to do next. This paper provides insights into the challenges that people
      face in making decisions at any time, but particularly during emergencies and
      crises. It also introduces the reader to the concept of different sense
      making/decision-making domains, the human behaviours that can adversely affect
      decision making - decision derailers - and ways in which emergency responders can
      leverage this knowledge to make better decisions. While the literature on
      decision making is extensive, this paper is focused on those aspects that apply
      particularly to decision making in emergencies or times of crisis. 

PMID- 24113639
TI  - Developing an ontological explosion knowledge base for business continuity
      planning purposes.
AB  - Industrial accidents are among the most known challenges to business continuity.
      Many organisations have lost their reputation following devastating accidents. To
      manage the risks of such accidents, it is necessary to accumulate sufficient
      knowledge regarding their roots, causes and preventive techniques. The required
      knowledge might be obtained through various approaches, including databases.
      Unfortunately, many databases are hampered by (among other things) static data
      presentations, a lack of semantic features, and the inability to present accident
      knowledge as discrete domains. This paper proposes the use of Protege software to
      develop a knowledge base for the domain of explosion accidents. Such a structure
      has a higher capability to improve information retrieval compared with common
      accident databases. To accomplish this goal, a knowledge management process model
      was followed. The ontological explosion knowledge base (EKB) was built for
      further applications, including process accident knowledge retrieval and risk
      management. The paper will show how the EKB has a semantic feature that enables
      users to overcome some of the search constraints of existing accident databases. 

PMID- 24113640
TI  - Part two: against the motion. young patients with good risk factors should not be
      treated with EVAR.

PMID- 24113641
TI  - Antioxidant and photoprotective effects of blanch water, a byproduct of the
      almond processing industry.
AB  - The aim of the present work was to evaluate the antioxidant and photoprotective
      effect of blanch water (BW), a byproduct of the almond processing industry. The
      polyphenolic content of a BW extract, the level of proanthocyanidins and the
      vanillin index determination were determined. The antioxidant activity and the
      radical scavenging activity of the BW were evaluated by a range of in vitro
      tests. The in vivo photoprotective effect was investigated using a formulation
      containing 2% of the BW extract on skin erythema induced by acute UV-B exposure
      in twelve volunteers. Results confirmed the presence of added-value antioxidant
      compounds in the industrial BW extract, and the most representative compounds
      were naringenin-7-O-glucoside and kaempferol-7-O-rutinoside. The proanthocyanidin
      content was 71.84 +/- 5.21 cyanidin equivalents/g of BW extract. The good
      antiradical activity of the BW extract was demonstrated in both the DPPH* test
      and in the Reducing Power test. The percentage inhibition of erythema obtained
      using a formulation of BW was 50.48, value clearly demonstrating an effect
      against photooxidative damage in vivo. 

PMID- 24113642
TI  - Evolutionary history predicts the stability of cooperation in microbial
      communities.
AB  - Cooperation fundamentally contributes to the success of life on earth, but its
      persistence in diverse communities remains a riddle, as selfish phenotypes
      rapidly evolve and may spread until disrupting cooperation. Here we investigate
      how evolutionary history affects the emergence and spread of defectors in
      multispecies communities. We set up bacterial communities of varying diversity
      and phylogenetic relatedness and measure investment into cooperation (proteolytic
      activity) and their vulnerability to invasion by defectors. We show that
      evolutionary relationships predict the stability of cooperation: phylogenetically
      diverse communities are rapidly invaded by spontaneous signal-blind mutants
      (ignoring signals regulating cooperation), while cooperation is stable in closely
      related ones. Maintenance of cooperation is controlled by antagonism against
      defectors: cooperators inhibit phylogenetically related defectors, but not
      distant ones. This kin-dependent inhibition links phylogenetic diversity and
      evolutionary dynamics and thus provides a robust mechanistic predictor for the
      persistence of cooperation in natural communities. 

PMID- 24113643
TI  - [Retinal damage caused by a metallic intraocular foreign body].

PMID- 24113644
TI  - A microfluidic approach to synthesizing high-performance microfibers with tunable
      anhydrous proton conductivity.
AB  - Here, we demonstrate a new approach for the synthesis of ion exchange microfibers
      with finely tuned anhydrous conductivity. This work presents microfluidics as a
      system to control the size and phosphoric acid (PA) doping level of the
      polybenzimidazole (PBI) microfibers. It has been shown that the PA doping level
      can be controlled by varying the flow ratios in the microfluidic channel. The
      diameter of the microfibers increased with extending mixing time, whereas the
      doping level decreased with increasing flow ratio. The highest doping level, 16,
      was achieved at the flow ratio of 0.175. The anhydrous proton conductivity of the
      microfibers was found to be adjustable between 0.01 and 0.1 S cm(-1) at 160 
      degrees C, which is considerably higher than for conventionally doped PBI cast
      membranes (0.004 S cm(-1)). Furthermore, molecular dynamic simulation of proton
      conduction through the microfibers at different doping levels was in good
      agreement with the experimental results. These results demonstrate the potential
      of the microfluidic technique to precisely tune the physicochemical properties of
      PBI microfibers for various electrochemical applications such as hydrogen
      sensors, fuel cells as well as artificial muscles. 

PMID- 24113645
TI  - Increased risk of intraoperative awareness in patients with a history of
      awareness.
AB  - BACKGROUND: Patients with a history of intraoperative awareness with explicit
      recall (AWR) are hypothesized to be at higher risk for AWR than the general
      surgical population. In this study, the authors assessed whether patients with a
      history of AWR (1) are actually at higher risk for AWR; (2) receive different
      anesthetic management; and (3) are relatively resistant to the hypnotic actions
      of volatile anesthetics. METHODS: Patients with a history of AWR and matched
      controls from three randomized clinical trials investigating prevention of AWR
      were compared for relative risk of AWR. Anesthetic management was compared with
      the use of the Hotelling's T statistic. A linear mixed model, including
      previously identified covariates, assessed the effects of a history of AWR on the
      relationship between end-tidal anesthetic concentration and bispectral index.
      RESULTS: The incidence of AWR was 1.7% (4 of 241) in patients with a history of
      AWR and 0.3% (4 of 1,205) in control patients (relative risk = 5.0; 95% CI, 1.3
      19.9). Anesthetic management did not differ between cohorts, but there was a
      significant effect of a history of AWR on the end-tidal anesthetic concentration
      versus bispectral index relationship. CONCLUSIONS: Surgical patients with a
      history of AWR are five times more likely to experience AWR than similar patients
      without a history of AWR. Further consideration should be given to modifying
      perioperative care and postoperative evaluation of patients with a history of
      AWR.

PMID- 24113646
TI  - Neural and immune consequences of traumatic brain injury: does propofol reduce
      the impact?

PMID- 24113647
TI  - Complications of laryngeal masks in children: big data comes to pediatric
      anesthesia.

PMID- 24113648
TI  - Cu-Zn powders as potential Cr(VI) adsorbents for drinking water.
AB  - This work examines the possibility of applying CuZn alloys as a reducing medium
      for the efficient removal of hexavalent chromium from drinking water. In an
      effort to develop a route for producing powders of CuZn alloys under mild
      conditions and investigate the optimum composition for such application, a series
      of alloys in the form of powders were prepared, by a sequence of Cu and Zn ball
      milling and low temperature annealing. Batch Cr(VI) removal tests, performed to
      evaluate and compare the efficiency of the products under typical natural water
      parameters (pH 7 and natural-like water), indicated that the best performing
      material have a composition around 50 wt% Cu. The dominant reduction mechanisms
      are both the corrosion of the alloy surface and the electron transfer to the
      solution. The behavior of granulated CuZn media was tested in rapid-scale column
      tests using the commercial KDF which verified the high potential of CuZn alloys
      in Cr(VI) removal. Nevertheless, Cu and Zn leaching problems should be also
      considered.

PMID- 24113649
TI  - Flame spray pyrolysis for sensing at the nanoscale.
AB  - Progress in developing novel gas sensors based on semiconducting metal oxides
      (SMOX) has been hindered by the cumbersome fabrication technologies currently
      employed. They involve time intensive synthesis procedures for gaining sensitive
      materials and preparation of the inks employed for realizing sensing layers. In
      this paper we review the opportunities offered by the relatively young method of
      flame spray pyrolysis, with which it is possible not only to synthesize a broad
      selection of SMOX in pure or doped form, but also to simultaneously deposit thick
      and highly porous gas sensitive films on a variety of substrates. In less than
      ten years the properties of nine base materials have been evaluated for all most
      relevant target gases and the obtained results are promising for future
      development. 

PMID- 24113650
TI  - The role of arthroscopy in chronic elbow instability.
AB  - PURPOSE: Elbow arthroscopy has had an emerging role in the management of many
      disorders of the elbow. In patients with chronic elbow instability, several
      arthroscopic techniques have been described in the diagnosis and management of
      posterolateral rotatory instability and valgus instability. METHODS: We performed
      a systematic review investigating the role of arthroscopy in posterolateral
      rotatory instability and valgus instability in the elbow using the PubMed and
      CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases, and
      the Cochrane Database of Systematic Reviews, consisting of articles from peer
      reviewed journals published in the English language after January 1, 1991.
      RESULTS: Search criteria initially identified 249 articles. Twenty-five articles
      met criteria for inclusion. This included 17 review articles, 4 cadaveric
      studies, 3 retrospective studies, and 1 prospective study. Two of the
      retrospective studies compared arthroscopic and open techniques. Articles
      included in this systematic review concluded that arthroscopy is an accurate
      adjunct to physical examination and imaging in the diagnosis of chronic elbow
      instability and affords an exceptional view of the joint with the ability to
      address intra-articular pathologic conditions. Arthroscopic surgical techniques
      have shown equivalent clinical outcomes in a comparison of arthroscopic and open
      techniques. CONCLUSIONS: Elbow arthroscopy is a valuable tool in the diagnosis
      and management of chronic elbow instability. Patients treated arthroscopically
      benefit from additional diagnostic techniques, improved visualization of the
      elbow joint, the ability to address coexisting intra-articular pathologic
      conditions, and minimal soft tissue injury with no clinical consequences in
      outcomes. With such significant advantages, the use of elbow arthroscopy is
      likely to expand in the management of chronic elbow instability. LEVEL OF
      EVIDENCE: Level IV, systematic review.

PMID- 24113651
TI  - Modeling biofilms with dual extracellular electron transfer mechanisms.
AB  - Electrochemically active biofilms have a unique form of respiration in which they
      utilize solid external materials as terminal electron acceptors for their
      metabolism. Currently, two primary mechanisms have been identified for long-range
      extracellular electron transfer (EET): a diffusion- and a conduction-based
      mechanism. Evidence in the literature suggests that some biofilms, particularly
      Shewanella oneidensis, produce the requisite components for both mechanisms. In
      this study, a generic model is presented that incorporates the diffusion- and the
      conduction-based mechanisms and allows electrochemically active biofilms to
      utilize both simultaneously. The model was applied to S. oneidensis and Geobacter
      sulfurreducens biofilms using experimentally generated data found in the
      literature. Our simulation results show that (1) biofilms having both mechanisms
      available, especially if they can interact, may have a metabolic advantage over
      biofilms that can use only a single mechanism; (2) the thickness of G.
      sulfurreducens biofilms is likely not limited by conductivity; (3) accurate
      intrabiofilm diffusion coefficient values are critical for current generation
      predictions; and (4) the local biofilm potential and redox potential are two
      distinct parameters and cannot be assumed to have identical values. Finally, we
      determined that simulated cyclic and squarewave voltammetry based on our model
      are currently not capable of determining the specific percentages of
      extracellular electron transfer mechanisms in a biofilm. The developed model will
      be a critical tool for designing experiments to explain EET mechanisms. 

PMID- 24113653
TI  - Generation and characterization of a rabbit monoclonal antibody site-specific for
      tau O-GlcNAcylated at serine 400.
AB  - Aggregation of tau into paired helical filaments is a pathological process
      leading to neurotoxicity in Alzheimer's disease and other tauopathies. Tau is
      posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc), and
      increasing tau O-GlcNAcylation may protect against its aggregation. Research
      tools to study the relationship between tau aggregation and tau O-GlcNAcylation
      have not been widely available. Here we describe the generation of a rabbit
      monoclonal antibody specific for tau O-GlcNAcylated at Ser400 (O-tau(S400)). We
      show the utility of this antibody for in vitro and in vivo experiments to
      investigate the function of O-GlcNAc modifications of tau at Ser400. 

PMID- 24113654
TI  - Remaining structures at the N- and C-terminal regions of alpha-synuclein
      accurately elucidated by amide-proton exchange NMR with fitting.
AB  - Alpha-synuclein is analyzed in physiological conditions by CLEANEX-PM
      methodology, in which the amide-proton exchange can be monitored at millisecond
      scale. The relationship between kex and [OH](-) is confirmed as a linear
      correlation with slope 1, indicating EX2 regime. There are significant residual
      structures at the N- and C-terminal regions. The structure at the C-terminal
      region is more stable than that of the N-terminal region. The middle part
      including NAC region is not completely protected. The data acquired at various pH
      and mixing time conditions followed by linear fitting give accurate information
      about residual structures. 

PMID- 24113652
TI  - Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from
      adaptive responses to psychopathologies.
AB  - A proper response against stressors is critical for survival. In mammals, the
      stress response is primarily mediated by secretion of glucocorticoids via the
      hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines
      through adrenergic neurotransmission. Activation of these pathways results in a
      quick physical response to the stress and, in adaptive conditions, mediates long
      term changes in the brain that lead to the formation of long-term memories of the
      experience. These long-term memories are an essential adaptive mechanism that
      allows an animal to effectively face similar demands again. Indeed, a moderate
      stress level has a strong positive effect on memory and cognition, as a single
      arousing or moderately stressful event can be remembered for up to a lifetime.
      Conversely, exposure to extreme, traumatic, or chronic stress can have the
      opposite effect and cause memory loss, cognitive impairments, and stress-related
      psychopathologies such as anxiety disorders, depression and post-traumatic stress
      disorder (PTSD). While more effort has been devoted to the understanding of the
      negative effects of chronic stress, much less has been done thus far on the
      identification of the mechanisms engaged in the brain when stress promotes long
      term memory formation. Understanding these mechanisms will provide critical
      information for use in ameliorating memory processes in both normal and
      pathological conditions. Here, we will review the role of glucocorticoids and
      glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore,
      we will discuss recent findings on the molecular cascade of events underlying the
      effect of GR activation in adaptive levels of stress that leads to strong, long
      lasting memories. Our recent data indicate that the positive effects of GR
      activation on memory consolidation critically engage the brain-derived
      neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis
      that stress promotes the formation of strong long-term memories because the
      activation of hippocampal GRs after learning is coupled to the recruitment of the
      growth and pro-survival BDNF/cAMP response element-binding protein (CREB)
      pathway, which is well-know to be a general mechanism required for long-term
      memory formation. We will then speculate about how these results may explain the
      negative effects of traumatic or chronic stress on memory and cognitive
      functions. 

PMID- 24113656
TI  - O-glycosylation of the non-canonical T-cadherin from rabbit skeletal muscle by
      single mannose residues.
AB  - O-mannosylation is a vital protein modification. In humans, defective O
      mannosylation of alpha-dystroglycan results in severe congenital muscular
      dystrophies. However, other proteins bearing this modification in vivo are still
      largely unknown. Here, we describe a highly reliable method combining glycosidase
      treatment with LC-MS analyses to identify mammalian O-mannosylated proteins from
      tissue sources. Our workflow identified T-cadherin (H-cadherin, CDH13) as a novel
      O-mannosylated protein. In contrast to known O-mannosylated proteins, single
      mannose residues (Man-alpha-Ser/Thr) are attached to this cell adhesion molecule.
      Conserved O-glycosylation sites in T-, E- and N-cadherins from different species,
      point to a general role of O-mannosyl glycans for cadherin function. 

PMID- 24113655
TI  - Prolyl isomerase Pin1 enhances osteoblast differentiation through Runx2
      regulation.
AB  - Peptidyl-prolyl isomerase 1 (Pin1) is the only enzyme known to catalyze
      isomerization of the pSer/Thr-Pro peptide bond. Pin1 induces conformational
      change of substrates and subsequently regulates diverse cellular processes.
      However, its role in osteoblast differentiation is not well understood. Here we
      show that Pin1 enhances osteoblast differentiation. Pin1 interacts and affects
      the protein stability and transcriptional activity of an important osteogenic
      transcriptional factor Runx2. Our results indicate that this regulation is likely
      due to suppression of poly-ubiquitination-mediated proteasomal degradation of
      Runx2. Our current finding suggests that Pin1 is a novel regulator of osteoblast
      differentiation that acts through the regulation of Runx2 function. 

PMID- 24113657
TI  - Structural and functional relationships of natural and artificial dimeric bovine
      ribonucleases: new scaffolds for potential antitumor drugs.
AB  - Protein aggregation via 3D domain swapping is a complex mechanism which can lead
      to the acquisition of new biological, benign or also malignant functions, such as
      amyloid deposits. In this context, RNase A represents a fascinating model system,
      since by dislocating different polypeptide chain regions, it forms many diverse
      oligomers. No other protein displays such a large number of different quaternary
      structures. Here we report a comparative structural analysis between natural and
      artificial RNase A dimers and bovine seminal ribonuclease, a natively dimeric
      RNase with antitumor activity, with the aim to design RNase A derivatives with
      improved pharmacological potential. 

PMID- 24113658
TI  - Interplay between polymerase II- and polymerase III-assisted expression of
      overlapping genes.
AB  - Up to 15% of the genes in different genomes overlap. This architecture, although
      beneficial for the genome size, represents an obstacle for simultaneous
      transcription of both genes. Here we analyze the interference between RNA
      polymerase II (Pol II) and RNA-polymerase III (Pol III) when transcribing their
      target genes encoded on opposing strands within the same DNA fragment in
      Arabidopsis thaliana. The expression of a Pol II-dependent protein-coding gene
      negatively correlated with the transcription of a Pol III-dependent, tRNA-coding
      gene set. We suggest that the architecture of the overlapping genes introduces an
      additional layer of control of gene expression. 

PMID- 24113659
TI  - Addressing the controversy of rate-versus-rhythm control in atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia and
      significantly increases patient risk of stroke, cardiomyopathy, and mortality.
      Rate versus rhythm control as the "best" treatment strategy remains an issue of
      considerable, ongoing debate. A multitude of clinical trials have compared the 2
      strategies and have not shown any benefit of one approach over the other.
      However, the trials were conducted in specific subgroups of patients and
      demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high
      incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that
      successful rhythm control with sinus rhythm restoration is associated with a
      significant reduction in patient mortality. More recently, radiofrequency
      ablation (RFA) has emerged as a relatively effective procedure for maintaining
      sinus rhythm compared with use of AADs. Prospective randomized studies have shown
      good treatment results after the use of RFA, with acceptable risk. Given the
      limitation of pharmacologic rate versus rhythm control studies, and the promise
      of RFA, rhythm control should again be reconsidered as the "best" approach for
      managing many subgroups of patients with atrial fibrillation. 

PMID- 24113660
TI  - Use of antiplatelet agents in patients with atherosclerotic disease.
AB  - Platelets play a key role in the initiation of hemostatic mechanisms during
      vascular injury. When contemplating prescription of antiplatelet agents (APAs)
      for patients as primary prevention for cardiovascular events, the physician
      should carefully weigh the potential benefits of cardiovascular risk reduction
      with the likelihood of harm, related mostly to hemorrhagic complications. The
      role of APAs in secondary prevention of atherosclerosis and coronary artery
      disease is well established, however, optimal duration of therapy and intensity
      of patient treatment are not settled and probably need to be individualized per
      patient. We describe the data emerging from contemporary trials on the efficacy
      and safety of the use of oral APAs in various patient subpopulations. We also
      discuss the advantages and potential roles of new APAs during and following acute
      coronary syndromes, percutaneous coronary interventions, and symptomatic
      atherosclerosis. We propose certain strategies and directions for future research
      to enhance the safety and efficacy prevention by optimizing the beneficial
      effects of APAs along with other contemporary treatment modalities of primary and
      secondary prevention. 

PMID- 24113661
TI  - Transcatheter aortic valve replacement: techniques, complications, and bailout
      strategies.
AB  - Transcatheter aortic valve replacement has emerged as an alternative option for
      inoperable or very high-risk patients with severe aortic stenosis-however, there
      are serious complications associated with the procedure, such as patient
      mortality, stroke, conduction disturbances, paravalvular regurgitation, and
      vascular concerns. Our review focuses on the most common complications related to
      transcatheter aortic valve replacement procedures and potential bailout
      strategies and techniques. 

PMID- 24113662
TI  - Renal artery stenosis - an update.
AB  - Renal artery stenosis (RAS) is a common form of peripheral arterial disease. The
      most common cause of RAS is atherosclerosis. It is predominantly unilateral. The
      pathophysiologic mechanism stems from renal underperfusion resulting in the
      activation of the renin- angiotensin-aldosterone pathway. Even though the
      majority of patients with RAS are asymptomatic, it can clinically present with
      hypertension, nephropathy and congestive heart failure. This progressive disease
      can lead to resistant hypertension and end stage kidney failure. Screening
      patients for RAS with either Doppler ultrasonography, computed tomographic
      angiography, or magnetic resonance angiography is preferred. Adequate blood
      pressure control, goal-directed lipid-lowering therapy, smoking cessation, and
      other preventive measures form the foundation of management of patients with RAS.
      Catheter-based percutaneous revascularization with angioplasty and stenting
      showed modest clinical benefit for patients in small retrospective studies, but
      data from randomized clinical trials failed to confirm these beneficial results.
      The current ongoing Cardiovascular Outcomes in Renal Atherosclerotic Lesions
      (CORAL) trial may provide more concrete data regarding the role of stenting in
      RAS. Surgical revascularization is considered only if catheter-based
      revascularization is unsuitable or unsuccessful. The American College of
      Cardiology/American Heart Association guidelines on evaluation and management of
      patients with RAS provide the framework for determining individualized assessment
      and treatment plans for patients with RAS. 

PMID- 24113663
TI  - Intravitreal triamcinolone acetonide compared with bevacizumab for the treatment
      of patients with macular edema secondary to central retinal vein occlusion.
AB  - PURPOSE: To compare 12-month outcomes achieved using intravitreal triamcinolone
      acetonide (IVTA) injections with those achieved using intravitreal bevacizumab
      (IVB) injections for the treatment of patients with macular edema (ME) secondary
      to central retinal vein occlusion (CRVO). MATERIALS AND METHODS: Between 2007 and
      2011, 17 patient eyes were administered IVTA (4 mg/0.1 mL) and 30 patient eyes
      were administered IVB (1.25 mg/0.05 mL) injections for the treatment of ME
      secondary to CRVO. Patients were retrospectively evaluated within and between
      treatment groups. RESULTS: Patients in both groups (IVTA and IVB) were similar in
      terms of demographic characteristics. Improvements in log of the minimum angle of
      resolution-visual acuity (logMAR-VA) at 3-month follow-up (P = 0.02), and in the
      logarithmic transformation of optical coherence tomography (OCT)-determined
      central subfoveal thickness (logOCT) at all visits, were significantly greater in
      the IVTA-treated group than in the group treated with IVB (P < 0.05). In patient
      eyes with nonischemic CRVO (n = 21), while no significant difference in
      improvement in logMAR-VA was seen between the groups, significantly greater
      improvements in logOCT were observed in the IVTA-treated group for all visits (P
      < 0.05). In patient eyes with ischemic CRVO (n = 26) treated with IVTA (n = 9),
      improvement in logMAR-VA was significantly greater at months 1 and 3 (P = 0.01),
      and was significantly greater for logOCT at months 6 and 12 (P < 0.05). A
      significantly higher percentage (29.4%) of eyes treated with IVTA had an
      intraocular pressure >= 30 mm Hg (P = 0.004), 2 eyes (11%) developed glaucoma,
      and 23.5% of eyes developed cataracts at the 12-month follow-up examination (P =
      0.05). CONCLUSION: Treatment with IVTA injections seems to be more effective in
      improving best-corrected visual acuity during the early postinjection period in
      patients with ischemic CRVO, and in decreasing central subfoveal thickness in
      patients with nonischemic CRVO. However, higher intraocular pressure and
      development of glaucoma and cataracts must be considered seriously in patients
      with CRVO who receive IVTA injections. Change in logOCT may be used to monitor
      patient response to treatments for CRVO-related ME.

PMID- 24113664
TI  - Impact of an electronic medical record system on emergency department discharge
      instructions for patients with hypertension.
AB  - BACKGROUND: Uncontrolled hypertension is associated with significant patient
      morbidity and health care costs. Many patients evaluated in the emergency
      department (ED) do not regularly consult health care providers and have
      socioeconomic barriers to receiving primary care. Hypertension screening and
      counseling has been advocated as a routine part of ED care. Previous work has
      shown poor referral rates and education for ED patients presenting with elevated
      blood pressure (BP). We sought to determine whether implementation of an
      electronic medical record (EMR) would improve these rates. METHODS: We performed
      a retrospective study conducted in 2 urban academic EDs, comparing pre-EMR
      (handwritten discharge) to post-EMR discharge instructions for patient referral
      for BP management and education on lifestyle modification. Medical records of
      patients aged >= 18 years with a systolic BP rate >= 140 or diastolic BP rate >=
      90 mm Hg were included. Patient data included demographics, BP rate, presenting
      symptoms, and administration of antihypertensive medication while in the ED.
      Discharge instructions were reviewed for a directed referral for outpatient BP
      management, prescriptions for antihypertensive medication, and lifestyle
      modifications. RESULTS: Of the 1000 medical records reviewed, 500 were pre- and
      500 were post-EMR, including a total of 389 patients who had persistently
      elevated BP on reassessment. At discharge, acknowledgment of elevated BP occurred
      in 45% of patients in the pre-EMR phase and only 26% in the post-EMR phase (P <
      0.0001). Provision of all 5 lifestyle modifications occurred in none of the pre
      EMR patients and in 15% of the post-EMR patients (P < 0.0001). Factors associated
      with a directed referral for the patient included increasing BP rate,
      pharmacologic treatment of hypertension in the ED, or provision of a prescription
      for an antihypertensive medication at discharge. The post-EMR phase was
      negatively associated with a directed referral for outpatient BP management.
      CONCLUSION: Overall, the initiation of EMR led to a decrease in outpatient
      referrals and acknowledgment of elevated BP rates in discharge instructions. The
      provision of more complete lifestyle modifications improved in the post-EMR
      phase.

PMID- 24113665
TI  - Treatment of the obese patient in primary care: targeting and meeting goals and
      expectations.
AB  - Obesity is a serious disease associated with increased patient risk of several
      comorbidities, including type 2 diabetes mellitus, cardiovascular disease,
      dyslipidemia, hypertension, some cancers, and greater mortality. Furthermore,
      obesity has a deleterious impact on quality of life and increases health care
      costs. Moderate weight loss of 5% to 10% has been shown to significantly improve
      several patient cardiometabolic risk factors and physical functioning, however,
      it is often difficult to begin the weight-loss conversation with patients.
      Primary care providers play a critical role in discussing the health effects of
      excess weight with patients, managing obesity-related comorbidities, and
      recommending appropriate weight-loss strategies. Open communication, realistic
      goal setting, and consistent monitoring are key factors in implementing an
      effective weight-loss program in the primary care setting. Although diet and
      lifestyle modifications are the first lines of approach and the foundation of any
      weight-loss strategy, in many cases, additional interventions may be necessary,
      including medical or surgical management. Herein, we discuss the approaches that
      primary care providers should consider when recommending appropriate weight-loss
      strategies for overweight/obese patients to achieve clinically meaningful weight
      loss, including pharmacotherapies approved for chronic management of patients
      with obesity, to be used as adjuncts to diet and lifestyle modifications, and
      surgical options. 

PMID- 24113666
TI  - Herpes zoster: diagnostic, therapeutic, and preventive approaches.
AB  - Herpes zoster (Hz), which generally presents as a localized, painful cutaneous
      eruption, is a common clinical problem, particularly among adults >= 50 years of
      age and immunocompromised patients. The diagnosis of Hz is mainly made
      clinically, except in patients with atypical manifestations or certain
      complications, such as central nervous system involvement, in which laboratory
      virologic testing is required. In addition to having a higher mortality rate,
      immunocompromised individuals have atypical and severe clinical findings and are
      at greater risk for complications and recurrence of Hz. Treatment of Hz includes
      the use of antiviral agents, analgesics for control of acute zoster pain, good
      skin care for healing, and prevention of secondary bacterial infection. Antiviral
      agents, preferably valacyclovir or famciclovir, should be started within 72 hours
      of onset to reduce the severity of the infection, the duration of the eruptive
      phase, and the intensity of acute pain. Herpes zoster has been associated with
      several complications, of which post-herpetic neuralgia (PHN) is the most common
      and debilitating. Varicella-zoster virus vaccine and early treatment with either
      famciclovir or valacyclovir are the only measures proven to prevent PHN. The
      options for treating PHN include topical agents, such as lidocaine patches, and
      systemic agents, such as the anticonvulsants gabapentin and pregabalin. Measures
      for preventing Hz include infection control through routine hand hygiene and
      appropriate use of isolation precautions and personal protective equipment;
      immunoglobulins, such as the varicella-zoster virus immunoglobulin and vaccine;
      and antiviral agents. The zoster vaccine has been shown to be effective in
      reducing the incidence of Hz and PHN. The vaccine is recommended for all
      individuals aged >= 60 years who have no contraindications, including individuals
      who report a previous episode of Hz. 

PMID- 24113667
TI  - Impact of sodium glucose cotransporter 2 inhibitors on weight in patients with
      type 2 diabetes mellitus.
AB  - Most patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Both
      T2DM and overweight/obesity are associated with increased patient risk of
      cardiovascular events and mortality. Despite being the recognized cornerstone of
      treatment, weight loss and maintenance of weight loss are difficult for patients
      with T2DM, particularly as treatments for T2DM may cause weight gain. Sodium
      glucose cotransporter 2 (SGLT2) inhibitors, a new class of drug for the treatment
      of patients with T2DM, reduce renal glucose reabsorption, resulting in urinary
      glucose excretion. Due to the caloric loss associated with decreased glucose in
      urine, treatment with SGLT2 agents offers the benefit of weight loss to patients,
      as well as reduction in hyperglycemia. Clinical trials of SGLT2 inhibitors in
      patients with T2DM, ranging in length from 4 to 90 weeks, have shown patient
      weight reductions from baseline of up to 4.7 kg. Such weight loss may have
      beneficial effects on adherence to medication, glycemic control, and
      cardiovascular risk in patients with T2DM. 

PMID- 24113668
TI  - Exenatide once weekly versus daily basal insulin as add-on treatment to metformin
      with or without a sulfonylurea: a retrospective pooled analysis in patients with
      poor glycemic control.
AB  - Basal insulin (b-INS) is typically the add-on treatment of choice for patients
      with poor glycemic control (ie, glycated hemoglobin [HbA1c] level >= 8.5%), but
      it is unclear whether b-INS is the best option. In this post hoc analysis, the
      efficacy and tolerability of exenatide once weekly (EQW) were compared with those
      of b-INS in patients with type 2 diabetes mellitus and a baseline HbA1c level
      8.5% who were undergoing treatment with metformin +/- a sulfonylurea. Data were
      pooled from two 26-week, randomized, controlled trials (EQW vs insulin glargine
      and EQW vs insulin detemir [EQW, N = 137; b-INS, N = 126]). Treatment with either
      EQW or b-INS for 26 weeks was associated with significant improvements in HbA1c
      level compared with baseline, although patients treated with EQW experienced a
      significantly greater decrease in HbA1c level than those treated with b-INS
      (least squares [LS] mean +/- SE: -2.0% +/- 0.08% vs -1.6% +/- 0.08%; P = 0.0008).
      Treatment with EQW was associated with a weight loss of 2.4 kg +/- 0.23 kg (LS
      mean +/- SE), whereas treatment with b-INS was associated with a weight gain of
      2.0 kg +/- 0.24 kg (LS mean difference between groups, -4.4 kg +/- 0.33; P <
      0.0001). Patients in the EQW group were significantly more likely to achieve the
      composite endpoint of an HbA1c level < 7.0%, no weight gain, and no hypoglycemic
      events (defined as a blood glucose level < 54 mg/dL requiring self-treatment or
      assistance to resolve) than patients in the b-INS group (33.6% vs 3.2%; P <
      0.0001). The exposure-adjusted hypoglycemic event rates were 0.08 and 0.37 events
      per patient-year in the EQW and b-INS groups, respectively. Gastrointestinal
      adverse events occurred at a higher rate in patients who underwent EQW treatment
      than those who were treated with b-INS. These results show that EQW treatment was
      associated with significantly greater improvement in HbA1c level compared with b
      INS treatment among patients with poor glycemic control, with the added benefits
      of weight loss (vs weight gain with b-INS therapy) and a lower incidence of
      hypoglycemic events. These results suggest that EQW is an alternative treatment
      to b-INS for patients with type 2 diabetes mellitus and a baseline HbA1c level >=
      8.5%. 

PMID- 24113669
TI  - Prostate cancer and the increasing role of active surveillance.
AB  - Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second
      leading cause of cancer-related death among men in the United States. As a
      result, for many years the American Urological Association (AUA) and the American
      Cancer Society have issued statements recommending screening for PC, resulting in
      its widespread implementation in the United States. Recently, the United States
      Preventative Services Task Force gave PC screening a recommendation of D, that
      is, against PC screening for all men. The AUA countered this recommendation,
      stating that since the development of PC screening using prostate-specific
      antigen, a reduction in PC-specific mortality has been seen, and that the risk
      reduction occurred in a setting in which many of the patients were not
      aggressively treated for prostate cancer. Active surveillance may be described as
      a method to potentially delay or obviate the need for treatment in men with
      clinically insignificant PC or PC thought to be at low risk for progression.
      Studies have shown no significant difference in outcome or pathology between men
      with low risk PC who receive treatment at the point of progression and those
      undergoing immediate treatment. Ongoing studies are evaluating the efficacy and
      utility of active surveillance for low-risk PC. Interim results of these studies
      have shown that approximately 30% of patients progress on active surveillance.
      However, "progression" does not necessarily mean treatment failure; rarely do
      patients develop locally advanced or metastatic disease. Active surveillance has
      also been shown to be cost-effective when compared with immediate treatment for
      PC. Longer follow-up may continue to show an increased benefit of active
      surveillance as a reasonable initial approach to the management of men with low
      risk, clinically localized PC. 

PMID- 24113670
TI  - Weight considerations in psychotropic drug prescribing and switching.
AB  - Our review describes potential weight-altering effects of psychotropic
      medications (antipsychotics, antidepressants, anti-anxiety medications, mood
      stabilizers, sedative-hypnotics, medications for attention-deficit/hyperactivity
      disorder, and other psychotropic medications) and offers guidance on switching a
      medication if its weight-altering effect becomes problematic. For second
      generation antipsychotics, the risk of weight gain is high with clozapine and
      olanzapine, low with amisulpride, aripiprazole, and ziprasidone, and medium with
      other second-generation antipsychotics. Switching from a high-risk antipsychotic
      to a low-risk antipsychotic usually mitigates or reverses weight gain. For second
      generation antidepressants, there may be modest weight loss with bupropion and
      modest weight gain with mirtazapine and paroxetine. Other second-generation
      antidepressants are weight neutral but individual variations can occur. If
      significant change in weight occurs, switching to or adding a low-risk second
      generation antidepressant should be considered. Mood stabilizers include lithium,
      valproate, carbamazepine, lamotrigine, oxcarbazepine, and most second-generation
      antipsychotics. Risk of weight gain is high with lithium and valproate and low
      with carbamazepine, lamotrigine, and oxcarbazepine. Given the complexity of
      bipolar disorder and its management, a switch of a mood stabilizer would be best
      done by a psychiatrist. Benzodiazepines, non-benzodiazepine and melatonergic
      hypnotics, doxepin, and trazodone are weight neutral. Diphenhydramine may cause
      weight-gain and can be switched to a weight-neutral hypnotic if needed.
      Stimulants can cause varying degrees of weight loss and switching to atomoxetine
      or bupropion may reverse this problem. If that fails, switching to clonidine or
      guanfacine can be tried. Switching must be evidence-based and take into account
      status of the condition being treated, efficacy, side effect profile, potential
      drug-drug interactions, required laboratory monitoring and cost of the drug(s)
      being considered, and patient's pregnancy status or plan. Non-pharmacological
      interventions both for mental disorders and overweight/obesity must be fully
      availed. 

PMID- 24113671
TI  - Lower-dose diclofenac submicron particle capsules provide early and sustained
      acute patient pain relief in a phase 3 study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs are prescribed for the
      treatment of patients with acute pain but use of such analgesics is associated
      with dose-dependent adverse events (AEs). Diclofenac submicron particle capsules
      have been developed using SoluMatrix technology to provide analgesia at lower
      doses than available solid oral dosing forms. Our study evaluated the analgesic
      efficacy and safety of lower-dose diclofenac submicron particle capsules in
      patients with acute pain following elective surgery. METHODS: A phase 3,
      multicenter, double-blind study enrolled 428 patients, aged 18 to 65 years, with
      moderate-to-severe pain following bunionectomy under regional anesthesia.
      Patients experiencing a pain intensity rating of >= 40 mm on a 100-mm Visual
      Analog Scale were randomized to receive lower-dose diclofenac submicron particle
      capsules (35 or 18 mg, 3 times daily [TID]), celecoxib (200 mg, twice daily
      [BID], 400-mg loading dose), or placebo. The primary efficacy parameter was the
      overall (summed) pain intensity difference measured over 0 to 48 hours (SPID-48).
      Secondary efficacy parameters included pain intensity difference (PID) at
      scheduled assessments. RESULTS: Lower-dose diclofenac submicron particle capsules
      35 mg TID (524.05; P < 0.001), 18 mg TID (393.25; P = 0.010), and celecoxib 200
      mg BID (390.22; P = 0.011) demonstrated significant pain control compared with
      placebo (77.10) for the primary efficacy parameter, mean SPID-48. Diclofenac
      submicron particle capsules 35 mg TID (4.52) provided some pain control (higher
      mean PID) at 30 minutes following administration, in contrast to celecoxib 200 mg
      BID (0.80), diclofenac submicron particle capsules 18 mg TID (0.31), and placebo
      (0.12). Better pain control (PID) was noted across all active treatment groups at
      5 hours compared with placebo (P <= 0.03), and pain relief was sustained
      throughout the treatment period. The most frequent non-procedure-related AEs were
      nausea, headache, dizziness, and vomiting. CONCLUSION: Lower-dose diclofenac
      submicron particle capsules provided effective analgesia in this phase 3 clinical
      study in patients with acute pain and are a potentially promising option for the
      treatment of patients with acute pain.

PMID- 24113672
TI  - Asterixis related to gabapentin intake: a case report and review.
AB  - Asterixis has been reported as a side effect of toxic and metabolic
      abnormalities. The current literature contains very little evidence of gabapentin
      related neurotoxicity. Our observations reveal that neurotoxic side effects of
      gabapentin use may be seen even when dose adjustments are made for patients with
      mild-to-moderate renal dysfunction. Clinical vigilance for possible neurotoxic
      effects of gabapentin therapy in patients with renal dysfunction is warranted. 

PMID- 24113673
TI  - A case report that suggested that aspirin's effects on valproic acid metabolism
      may contribute to valproic acid's inducer effects on clozapine metabolism.

PMID- 24113674
TI  - Population pharmacokinetic-pharmacodynamic modeling of haloperidol in patients
      with schizophrenia using positive and negative syndrome rating scale.
AB  - The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PKPD)
      model that quantifies the efficacy of haloperidol, accounting for the placebo
      effect, the variability in exposure-response, and the dropouts. Subsequently, the
      developed model was utilized to characterize an effective dosing strategy for
      using haloperidol as a comparator drug in future antipsychotic drug trials. The
      time course of plasma haloperidol concentrations from 122 subjects and the
      Positive and Negative Syndrome Scale (PANSS) scores from 473 subjects were used
      in this analysis. A nonlinear mixed-effects modeling approach was utilized to
      describe the time course of PK and PANSS scores. Bootstrapping and simulation
      based methods were used for the model evaluation. A 2-compartment model
      adequately described the haloperidol PK profiles. The Weibull and Emax models
      were able to describe the time course of the placebo and the drug effects,
      respectively. An exponential model was used to account for dropouts. Joint
      modeling of the PKPD model with dropout model indicated that the probability of
      patients dropping out is associated with the observed high PANSS score. The model
      evaluation results confirmed that the precision and accuracy of parameter
      estimates are acceptable. Based on the PKPD analysis, the recommended oral dose
      of haloperidol to achieve a 30% reduction in PANSS score from baseline is 5.6
      mg/d, and the corresponding steady-state effective plasma haloperidol exposure is
      2.7 ng/mL. In conclusion, the developed model describes the time course of PANSS
      scores adequately, and a recommendation of haloperidol dose was derived for
      future antipsychotic drug trials. 

PMID- 24113675
TI  - Mirtazapine add-on improves olanzapine effect on negative symptoms of
      schizophrenia.

PMID- 24113676
TI  - Pseudopathologic vertebral body enhancement in the presence of superior vena cava
      obstruction on computed tomography.
AB  - BACKGROUND CONTEXT: Superior vena cava (SVC) obstruction can cause the
      development of collateral vessels. During contrast-enhanced thoracic computed
      tomography (CT), contrast material may reflux into the collaterals such as
      paravertebral venous plexus. However, an unusual pseudopathologic vertebral body
      enhancement on CT in the presence of SVC obstruction has not been studied
      previously. PURPOSE: To demonstrate clinical presentation and imaging findings of
      pseudopathologic vertebral body enhancement in patients with SVC obstruction.
      STUDY DESIGN: Retrospective study of diagnostic CT images examined at our clinic.
      PATIENT SAMPLE: From March, 2009 to September, 2012, a retrospective radiologic
      database review was performed to identify patients with obstruction of SVC
      causing contrast reflux into collateral vessels and presented with an unusual
      vertebral body enhancement on thoracic CT. Thirteen patients (11 men, mean age
      51.4 years) with vertebral body enhancement were enrolled. OUTCOME MEASURES:
      Enhancement patterns of vertebral bodies were classified as nodular enhancement
      with round shape occupying less than one-third of vertebral body or polygonal
      enhancement occupying greater than or equal to one-third of vertebral body on
      axial image. The locations of enhanced areas within vertebral bodies were
      described using right lateral/central/left lateral, anterior/posterior, and
      upper/middle/lower in the x-, y-, or z-axis directions, respectively. MATERIALS
      AND METHODS: Enhancement patterns, locations, and the presence of a connection
      between vertebral body enhancement and the paravertebral venous plexus were
      evaluated. RESULTS: A total of 39 vertebral body enhancements were found in the
      13 patients, involving cervical (n=12), thoracic (n=25), or lumbar (n=2)
      vertebrae. Vertebral body enhancements showed a nodular (n=19) or a polygonal
      (n=20) pattern. The central portions of vertebral bodies were more frequently
      involved. The connection to the paravertebral venous plexus was observed in 34
      lesions (87.2%). CONCLUSIONS: Patients with SVC obstruction with extensive
      collateral vessels might exhibit a pseudopathologic vertebral enhancement. They
      tended to involve the central portion of the vertebral body, and most of them
      showed connection to the paravertebral venous plexus.

PMID- 24113678
TI  - 2013 "Heads-up": medicare is preparing for ICD-10-CM. Are you?

PMID- 24113677
TI  - Torque modulates nucleosome stability and facilitates H2A/H2B dimer loss.
AB  - The nucleosome, the fundamental packing unit of chromatin, has a distinct
      chirality: 147 bp of DNA are wrapped around the core histones in a left-handed,
      negative superhelix. It has been suggested that this chirality has functional
      significance, particularly in the context of the cellular processes that generate
      DNA supercoiling, such as transcription and replication. However, the impact of
      torsion on nucleosome structure and stability is largely unknown. Here we perform
      a detailed investigation of single nucleosome behaviour on the high-affinity 601
      positioning sequence under tension and torque using the angular optical trapping
      technique. We find that torque has only a moderate effect on nucleosome
      unwrapping. In contrast, we observe a dramatic loss of H2A/H2B dimers on
      nucleosome disruption under positive torque, whereas (H3/H4)2 tetramers are
      efficiently retained irrespective of torsion. These data indicate that torque
      could regulate histone exchange during transcription and replication.

PMID- 24113679
TI  - Issues related to overadherence to oral chemotherapy or targeted agents.
AB  - Use of oral chemotherapy or targeted agents is shifting how cancer treatment is
      administered, moving it from supervised office visits to self-administration at
      home. This study examines issues related to overadherence to oral agents that
      were noted during a trial conducted by the authors comparing an automated voice
      system to strategies to reduce symptom severity and improve adherence.
      Overadherence to oral agents may be a significant clinical problem, occurring
      more often in patients with complex dosing regimens, and may lead to increased
      symptom severity from side effects of treatment. Avoiding overadherence may be
      important for the reduction or prevention of symptoms and potentially life
      threatening toxicity. Nurses need to discuss with their patients the importance
      of the timing of the administration of their oral oncolytic regimen, as well as
      to provide prompts to assist in self-administration as prescribed so that
      overadherence can be avoided. 

PMID- 24113680
TI  - Force sensitive handles and capacitive touch sensor for driving a flexible haptic
      based immersive system.
AB  - In this article, we present an approach that uses both two force sensitive
      handles (FSH) and a flexible capacitive touch sensor (FCTS) to drive a haptic
      based immersive system. The immersive system has been developed as part of a
      multimodal interface for product design. The haptic interface consists of a strip
      that can be used by product designers to evaluate the quality of a 3D virtual
      shape by using touch, vision and hearing and, also, to interactively change the
      shape of the virtual object. Specifically, the user interacts with the FSH to
      move the virtual object and to appropriately position the haptic interface for
      retrieving the six degrees of freedom required for both manipulation and
      modification modalities. The FCTS allows the system to track the movement and
      position of the user's fingers on the strip, which is used for rendering visual
      and sound feedback. Two evaluation experiments are described, which involve both
      the evaluation and the modification of a 3D shape. Results show that the use of
      the haptic strip for the evaluation of aesthetic shapes is effective and supports
      product designers in the appreciation of the aesthetic qualities of the shape. 

PMID- 24113681
TI  - Harmful gas recognition exploiting a CTL sensor array.
AB  - In this paper, a novel cataluminescence (CTL)-based sensor array consisting of
      nine types of catalytic materials is developed for the recognition of several
      harmful gases, namely carbon monoxide, acetone, chloroform and toluene. First,
      the experimental setup is constructed by using sensing nanomaterials, a heating
      plate, a pneumatic pump, a gas flow meter, a digital temperature device, a camera
      and a BPCL Ultra Weak Chemiluminescence Analyzer. Then, unique CTL patterns for
      the four types of harmful gas are obtained from the sensor array. The harmful
      gases are successful recognized by the PCA method. The optimal conditions are
      also investigated. Finally, experimental results show high sensitivity, long-term
      stability and good linearity of the sensor array, which combined with simplicity,
      make our system a promising application in this field. 

PMID- 24113682
TI  - Improving electronic sensor reliability by robust outlier screening.
AB  - Electronic sensors are widely used in different application areas, and in some of
      them, such as automotive or medical equipment, they must perform with an
      extremely low defect rate. Increasing reliability is paramount. Outlier detection
      algorithms are a key component in screening latent defects and decreasing the
      number of customer quality incidents (CQIs). This paper focuses on new spatial
      algorithms (Good Die in a Bad Cluster with Statistical Bins (GDBC SB) and Bad Bin
      in a Bad Cluster (BBBC)) and an advanced outlier screening method, called Robust
      Dynamic Part Averaging Testing (RDPAT), as well as two practical improvements,
      which significantly enhance existing algorithms. Those methods have been used in
      production in Freescale(r) Semiconductor probe factories around the world for
      several years. Moreover, a study was conducted with production data of 289,080
      dice with 26 CQIs to determine and compare the efficiency and effectiveness of
      all these algorithms in identifying CQIs. 

PMID- 24113683
TI  - A spherically-shaped PZT thin film ultrasonic transducer with an acoustic
      impedance gradient matching layer based on a micromachined periodically
      structured flexible substrate.
AB  - This paper presents the microfabrication of an acoustic impedance gradient
      matching layer on a spherically-shaped piezoelectric ultrasonic transducer. The
      acoustic matching layer can be designed to achieve higher acoustic energy
      transmission and operating bandwidth. Also included in this paper are a
      theoretical analysis of the device design and a micromachining technique to
      produce the novel transducer. Based on a design of a lead titanium zirconium
      (PZT) micropillar array, the constructed gradient acoustic matching layer has
      much better acoustic transmission efficiency within a 20-50 MHz operation range
      compared to a matching layer with a conventional quarter-wavelength thickness
      Parylene deposition. To construct the transducer, periodic microcavities are
      built on a flexible copper sheet, and then the sheet forms a designed curvature
      with a ball shaping. After PZT slurry deposition, the constructed PZT micropillar
      array is released onto a curved thin PZT layer. Following Parylene conformal
      coating on the processed PZT micropillars, the PZT micropillars and the
      surrounding Parylene comprise a matching layer with gradient acoustic impedance.
      By using the proposed technique, the fabricated transducer achieves a center
      frequency of 26 MHz and a -6 dB bandwidth of approximately 65%. 

PMID- 24113684
TI  - Thermal tracking in mobile robots for leak inspection activities.
AB  - Maintenance tasks are crucial for all kind of industries, especially in extensive
      industrial plants, like solar thermal power plants. The incorporation of robots
      is a key issue for automating inspection activities, as it will allow a constant
      and regular control over the whole plant. This paper presents an autonomous
      robotic system to perform pipeline inspection for early detection and prevention
      of leakages in thermal power plants, based on the work developed within the
      MAINBOT (http://www.mainbot.eu) European project. Based on the information
      provided by a thermographic camera, the system is able to detect leakages in the
      collectors and pipelines. Beside the leakage detection algorithms, the system
      includes a particle filter-based tracking algorithm to keep the target in the
      field of view of the camera and to avoid the irregularities of the terrain while
      the robot patrols the plant. The information provided by the particle filter is
      further used to command a robot arm, which handles the camera and ensures that
      the target is always within the image. The obtained results show the suitability
      of the proposed approach, adding a tracking algorithm to improve the performance
      of the leakage detection system. 

PMID- 24113685
TI  - Silicon carbide-based hydrogen gas sensors for high-temperature applications.
AB  - We investigated SiC-based hydrogen gas sensors with metal-insulator-semiconductor
      (MIS) structure for high temperature process monitoring and leak detection
      applications in fields such as the automotive, chemical and petroleum industries.
      In this work, a thin tantalum oxide (Ta2O5) layer was exploited with the purpose
      of sensitivity improvement, because tantalum oxide has good stability at high
      temperature with high permeability for hydrogen gas. Silicon carbide (SiC) was
      used as a substrate for high-temperature applications. We fabricated Pd/Ta2O5/SiC
      based hydrogen gas sensors, and the dependence of their I-V characteristics and
      capacitance response properties on hydrogen concentrations were analyzed in the
      temperature range from room temperature to 500  degrees C. According to the
      results, our sensor shows promising performance for hydrogen gas detection at
      high temperatures. 

PMID- 24113686
TI  - Micronutrient status in phenylketonuria.
AB  - Patients with phenylketonuria (PKU) encompass an 'at risk' group for
      micronutrient imbalances. Optimal nutrient status is challenging particularly
      when a substantial proportion of nutrient intake is from non-natural sources. In
      PKU patients following dietary treatment, supplementation with micronutrients is
      a necessity and vitamins and minerals should either be added to supplement
      phenylalanine-free l-amino acids or given separately. In this literature review
      of papers published since 1990, the prevalence of vitamin and mineral deficiency
      is described, with reference to age of treatment commencement, type of treatment,
      dietary compliance, and dietary practices. Biological micronutrient inadequacies
      have been mainly reported for zinc, selenium, iron, vitamin B12 and folate. The
      aetiology of these results and possible clinical and biological implications are
      discussed. In PKU there is not a simple relationship between the dietary intake
      and nutritional status, and there are many independent and interrelated complex
      factors that should be considered other than quantitative nutritional intake. 

PMID- 24113688
TI  - Hot spots in different metal nanostructures for plasmon-enhanced Raman
      spectroscopy.
AB  - Noble metal nanostructures are able to concentrate light into small volumes,
      which enhances greatly the local electromagnetic (EM) field near the metal
      nanostructures. The areas with greatly enhanced EM field become "hot spots" for
      surface-enhanced Raman spectroscopy (SERS), which utilizes the field enhancement
      properties of metal nanostructures to amplify the usually weak Raman scattering
      signals. The preparation of metal nanostructures with superior SERS performances
      is one of the main topics in the SERS field and is important for the applications
      of SERS in sensing and analysis. In this feature article, we review several
      different kinds of metal structures for SERS, including coupled metal
      nanostructures, nanostructure arrays, nano/micro structures with textured
      surfaces and graphene-mediated SERS substrates. Tip-enhanced Raman spectroscopy
      (TERS) using the metal tip of the scanning tunneling microscope is also
      discussed. Besides the intensity enhancement in SERS and TERS, some less studied
      aspects are highlighted; for example, the remote excitation technique, tuning the
      nanogap of gold nanorod dimers through strain control on an elastomeric
      substrate, manipulating Raman emission polarization using asymmetric
      nanoantennas, and investigating plasmon-enhanced chemical reactions by TERS. 

PMID- 24113687
TI  - Dietary management of urea cycle disorders: European practice.
AB  - BACKGROUND: There is no published data comparing dietary management of urea cycle
      disorders (UCD) in different countries. METHODS: Cross-sectional data from 41
      European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany,
      4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected
      by questionnaire describing management of patients with UCD on prescribed protein
      restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase
      (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29;
      ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108;
      argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported.
      The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y.
      Prescribed median protein intake/kg body weight decreased with age with little
      variation between disorders. The UK tended to give more total protein than other
      European countries particularly in infancy. Supplements of essential amino acids
      (EAA) were prescribed for 38% [n=174] of the patients overall, but were given
      more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%).
      Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most
      frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds,
      most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy
      supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between
      different conditions, and between and within European IMD centres. Further
      studies examining the outcome of treatment compared with the type of dietary
      therapy and nutritional support received are required.

PMID- 24113689
TI  - Silica nanoparticles for cell imaging and intracellular sensing.
AB  - There is increasing interest in the use of nanoparticles (NPs) for biomedical
      applications. In particular, nanobiophotonic approaches using fluorescence offers
      the potential of high sensitivity and selectivity in applications such as cell
      imaging and intracellular sensing. In this review, we focus primarily on the use
      of fluorescent silica NPs for these applications and, in so doing, aim to enhance
      and complement the key recent review articles on these topics. We summarize the
      main synthetic approaches, namely the Stober and microemulsion processes, and, in
      this context, we deal with issues in relation to both covalent and physical
      incorporation of different types of dyes in the particles. The important issue of
      NP functionalization for conjugation to biomolecules is discussed and strategies
      published in the recent literature are highlighted and evaluated. We cite recent
      examples of the use of fluorescent silica NPs for cell imaging in the areas of
      cancer, stem cell and infectious disease research, and we review the current
      literature on the use of silica NPs for intracellular sensing of oxygen, pH and
      ionic species. We include a short final section which seeks to identify the main
      challenges and obstacles in relation to the potential widespread use of these
      particles for in vivo diagnostics and therapeutics. 

PMID- 24113690
TI  - Construction of a microfluidic chip, using dried-down reagents, for LATE-PCR
      amplification and detection of single-stranded DNA.
AB  - LATE-PCR is an advanced form of non-symmetric PCR that efficiently generates
      single-stranded DNA which can readily be characterized at the end of
      amplification by hybridization to low-temperature fluorescent probes. We
      demonstrate here for the first time that monoplex and duplex LATE-PCR
      amplification and probe target hybridization can be carried out in double layered
      PDMS microfluidics chips containing dried reagents. Addition of a set of reagents
      during dry down overcomes the common problem of single-stranded oligonucleotide
      binding to PDMS. These proof-of-principle results open the way to construction of
      inexpensive point-of-care devices that take full advantage of the analytical
      power of assays built using LATE-PCR and low-temperature probes. 

PMID- 24113691
TI  - Enhanced ultraviolet responses in thin-film InGaP solar cells by down-shifting.
AB  - Layers of poly(methyl methacrylate) doped with the Eu complex Eu(DPEPO)(hfac)3
      (EuDH) provide a means for down-shifting incident ultraviolet (UV) light into the
      visible range, with beneficial effects on the performance of solar cells, as
      demonstrated with thin-film InGaP devices formed by epitaxial liftoff.
      Experimental and computational results establish important aspects of gain and
      loss mechanisms in the UV range. Measurements show that InGaP cells with coatings
      of EuDH doped PMMA exhibit enhanced currents (8.68 mA cm(-2)) and power
      conversion efficiencies (9.48%), both due to increased responses at wavelengths
      between 300-360 nm. 

PMID- 24113692
TI  - The post-cardiac arrest microcirculation: more than meets the eye?

PMID- 24113693
TI  - Starch structure modulates metabolic activity and gut microbiota profile.
AB  - Normal maize starch and high amylose maize starch (HAS) either in native or
      thermally treated forms were used to investigate the effect of starch structure
      on the production of metabolites and gut microbiota profile using an anaerobic in
      vitro system. The changes in starch structure during fermentation were
      investigated using scanning electron microscopy (SEM), high-performance liquid
      chromatography (HPLC) and Fourier transform infra-red spectroscopy (FTIR). The
      native normal starch showed a porous structure during fermentation, indicating it
      was quickly metabolized by gut bacteria, whereas the HAS showed a smooth
      structure, suggesting it was utilized gradually. HPLC chromatography showed that
      amylose fraction with low molecular weight (MW) had a higher resistance to be
      fermented by gut bacteria than other starch molecular fractions. Thermal
      treatment enhanced starch fermentation kinetics, especially for amylopectin and
      high MW amylose fractions. FTIR analysis suggests that the structure of the
      normal starch, either in native or thermally treated, was less organized compared
      to HAS, and this structural character led to the normal starch to be utilized
      more quickly by gut bacteria with a faster increase in the IR ratio 1047/1022 cm(
      1) (P < 0.01) during fermentation. The measurement of metabolic activity
      indicates that the normal starch with a less organized structure was utilized
      faster and generated more acetate and lactate during fermentation; HAS with a
      highly organized structure was more likely to produce butyrate, corresponding the
      significant increase (P < 0.001) in the populations of butyrate-producing strains
      (Faecalibacterium prausnitzii and Eubacterium hallii) in the cultures. This study
      reveals that fermentation kinetics of starch substrate is one of important
      characteristics for manipulating gut microbiota fermentation behaviours.

PMID- 24113696
TI  - Comparing rates of distal edge necrosis in deep-plane vs subcutaneous
      cervicofacial rotation-advancement flaps for facial cutaneous Mohs defects.
AB  - IMPORTANCE: The cervicofacial rotation-advancement flap is commonly used for
      facial defects. Decreasing the rate of distal edge necrosis (DEN) encountered
      with this flap would help prevent complications in sensitive areas such as the
      eyelid, lip, and nose. OBJECTIVE: To compare the untoward occurrence of DEN
      between 2 surgical dissection methods for reconstructive cervicofacial rotation
      advancement flaps. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: A review was
      conducted of 88 patients who underwent cervicofacial flap reconstruction for Mohs
      ablative surgery between January 1, 2003, and June 30, 2012, by the senior author
      (A.A.J.). All patients had periorbital, midfacial, cervical, and/or lateral
      temporal/forehead defects following Mohs surgical ablation. Patients were
      categorized into 1 of 2 groups on the basis of the surgical technique used:
      subcutaneous (SC) cervicofacial elevation or deep-plane (DP) cervicofacial
      elevation. Subcategories of smokers and nonsmokers within each group were further
      reviewed. Statistical analysis of DEN between categories and subcategories was
      performed. RESULTS: Sixty-nine patients were in the SC group and 19 were in the
      DP group. The mean defect size among both groups was 14.3 cm(2). The rate of
      active or recent smokers was 23% in the SC group and 11% in the DP group. The
      rate of DEN among nonsmokers in the SC group was 23% (n = 53) compared with 0% in
      the 17 DP nonsmokers (P = .03). The rate of smokers with DEN in the SC group was
      75% and 0% in the DP group (P = .09). The mean area of DEN in the SC group was
      0.8 cm(2). CONCLUSIONS AND RELEVANCE: Our statistically significant data indicate
      that DP dissection is a superior technique for avoiding DEN in nonsmokers. We
      found better outcomes in smokers as well. Thus, we strongly advocate the use of
      the DP approach as the criterion standard in cervicofacial flap elevation. LEVEL
      OF EVIDENCE: 3.

PMID- 24113694
TI  - Potential roles of arginine-vasotocin in the regulation of aggressive behavior in
      the mudskipper (Periophthalmus modestus).
AB  - The hypothalamic hormones, arginine-vasotocin (VT) and isotocin (IT), play
      central roles in osmoregulation and in the regulation of social behaviors
      including aggressive behavior in many vertebrates including fish. Here, we
      examined whether these hormones are associated with aggressive behavior in the
      mudskipper (Periophthalmus modestus). The mudskipper is an amphibious fish, which
      lives in the brackish water of river mouths and displays unique aggressive
      behavior. Upon introduction to each other in an experimental tank with aquatic
      and terrestrial areas, a pair of males can be classified as aggressive dominant
      or submissive subordinate based on the frequency of their aggressive acts, which
      is significantly higher in dominant male. Additionally, the length of stay in
      terrestrial area of dominant was longer than that of the subordinate. The latter
      remained in aquatic area almost throughout the period of behavioral observation.
      The expression of brain VT mRNA was significantly higher in subordinate than in
      dominant, whereas neither IT mRNA expression nor plasma cortisol level differed
      between subordinate and dominant male. On the other hand, an
      intracerebroventricular injection of VT increased aggressive behaviors in
      mudskippers. In addition to known roles of VT in mediation of aggressive
      behavior, these results may shed light on the role of endogenous VT toward water
      migration in submissive mudskippers. The amphibious fish is a valuable
      experimental model to observe the relationship between effects of central VT on
      the osmoregulation and social behavioral regulation in vertebrates. 

PMID- 24113697
TI  - [Polytrauma in children and adolescents. Choice of the primary care clinic and
      importance of pediatric traumatology competence centers].
AB  - BACKGROUND: The number of (seriously) injured children increased again for the
      first time in 2011. The aim of this study was to analyse differences compared to
      multiple injured adults and to show the reality of daily treatment. METHODS: All
      cases of the DGU Trauma Registry from the years 1997 to 2010 were examined. The
      documented cases were divided into different the age groups. The study
      investigated, e.g. the mechanism of accident, injury pattern, the number of
      hospital and ICU days, and lethality. RESULTS: At 38.8% the largest percentage of
      severely injured children and adolescents belongs to the group of 16-17 year
      olds. The group of 0-5 year olds (15.9%) has the lowest percentage. The most
      common accident cause was traffic accidents (58.5%). The mechanism of accident
      and the injury patterns changes with age. Younger patients are often treated in
      supraregional trauma centers (0-5 year olds: 78.2% vs. 16-17 year olds: 73.1% vs.
      > 65 years: 63.2%). The average lethality rate was 14.8% (16.3% RISC).
      CONCLUSIONS: The percentage of severely injured children in the overall
      population is only 7.4%. Because the majority of patients are primarily treated
      in supraregional trauma centers, trauma centers with specialisation in paediatric
      traumatology are mandatory.

PMID- 24113699
TI  - A review of the management of patellofemoral pain syndrome.
AB  - OBJECTIVE: Patellofemoral pain syndrome (PFPS) is one of the most frequently
      diagnosed knee conditions in the primary care, orthopedic, and sports medicine
      settings. Although strength training and stretching programs have traditionally
      been the mainstay of patient treatment, there are no consensus recovery protocols
      for runners experiencing PFPS. The purpose of our review is to examine recent
      literature regarding the efficacy of various treatment modalities in the
      management of patients with PFPS. METHODS: Our review included 33 articles from a
      PubMed literature search using the search term PFPS treatment. The search was
      limited to randomized controlled trials, crossover case-controlled studies, and
      cohort studies with >= 10 participants, with trial data that were published
      within the last 5 years. RESULTS: Strength training and stretching exercises
      continue to be strongly supported by research as effective treatment options for
      runners with PFPS. Recent studies have confirmed that quadriceps and hip
      strengthening combined with stretching in a structured physiotherapy program
      comprise the most effective treatment for reducing knee pain symptoms and
      improving functionality in patients with PFPS. As previous studies have shown,
      therapies such as proprioceptive training, orthotics, and taping may offer
      benefits as adjunctive therapies but do not show a significant benefit when they
      are used alone in patients with PFPS. Additionally, recent research has confirmed
      that surgical and pharmacologic therapies are not effective for the management of
      patients with PFPS. CONCLUSION: A large number of athletes are impacted by PFPS
      every year, particularly young runners. Sports medicine researchers have
      investigated many possible therapies for patients with PFPS; however, no clear
      guidelines have emerged regarding the management of the syndrome. Our review
      analyzes recent literature on PFPS and identifies specific treatment
      recommendations. The most effective and strongly supported treatment modality for
      patients with PFPS is a combined physiotherapy program, including strength
      training of the quadriceps and hip abductors and stretching of the quadriceps
      muscle group. Adjunctive therapies, including taping, biofeedback devices, and
      prefabricated orthotic inserts, may provide limited additive benefits in select
      populations. Surgery should be avoided in all patients with PFPS.

PMID- 24113698
TI  - Autologous bone marrow concentrate: review and application of a novel intra
      articular orthobiologic for cartilage disease.
AB  - Younger adults, aged < 65 years, increasingly present to their physicians with
      advanced cartilage disease or post-traumatic osteoarthritis. A number of
      treatments exist for lessening patient pain and improving patient function.
      However, many patients are becoming aware of the potential of regenerative
      therapies and are now seeking solutions to the impaired biology underlying their
      conditions rather than addressing only their symptoms. Patients do not want to
      merely lessen their symptoms temporarily with a surgical procedure that replaces
      damaged tissue, but instead seek correction and repair of the underlying biology
      to regenerate damaged tissue and alleviate their symptoms altogether. Current
      therapies for patients with cartilage disease or osteoarthritis range from non
      surgical intra-articular injections with biologics, such as hyaluronic acid (HA),
      to total joint arthroplasty for advanced stages of disease. Total joint
      arthroplasty is a successful procedure for patients aged > 65 years; however, the
      limited long-term durability of implanted prostheses decreases the preference of
      using such methods in more active patients aged < 65 years. The potential of cell
      based orthobiologic injection therapies (pertaining to therapeutic injectables
      that aim to restore the biologic environment and/or structural components of
      diseased or damaged musculoskeletal tissue) is of tremendous interest for
      younger, more active patients, and is even more appealing in that such therapy
      can be delivered at point-of-care in the clinic during an office visit. Notably,
      the exponential rate of progress in biotechnology has allowed for immediate
      application of myriad novel therapies prior to clear evidence of benefit from
      randomized clinical trials. Orthobiologic intra-articular injection therapies
      include HA and platelet-rich plasma (PRP). We report on current, available
      findings for a third-generation intra-articular orthobiologic injectable therapy
      for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate
      contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets
      (containing growth factors), and cytokines. The anti-inflammatory and
      immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate
      regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage
      repair by increasing aggrecan content and tissue firmness. Following bone marrow
      aspiration (BMA), BMC is easily prepared using centrifugation, and is available
      for a same-day procedure with minimal manipulation of cells, thus complying with
      US Food and Drug Association (FDA) restrictions. To date, there are no published
      randomized controlled trials on the efficacy of use of autologous BMC intra
      articular injections performed as a same-day in-office procedure for treating
      patients with cartilage disease; however, several publications have reported the
      ease of use of this method, its strong safety profile, and the fundamental
      science suggesting great therapeutic potential. 

PMID- 24113700
TI  - Cissus quadrangularis reduces joint pain in exercise-trained men: a pilot study.
AB  - BACKGROUND: Strenuous, high-volume exercise is often associated with inflammation
      and joint pain. Cissus quadrangularis (CQ) has been reported to have anti
      inflammatory activity. The purpose of our study was to determine the therapeutic
      effects of CQ supplementation in healthy, exercise-trained men with joint
      specific pain. METHODS: Twenty-nine men between the ages of 20 and 46 years, who
      reportedly experienced chronic joint pain as a result of strenuous exercise,
      participated in our pilot study. All men received CQ 3200 mg daily for 8 weeks.
      Before and after the 8-week intervention period, subjects completed a
      questionnaire to determine their degree of joint pain (Western Ontario and
      McMaster Universities Index of Osteoarthritis [WOMAC]). Clinical measures (eg,
      heart rate, blood pressure, blood biomarkers) were also collected for each
      subject pre- (baseline) and post-intervention. RESULTS: Subject ratings for
      multiple variables within the WOMAC Index improved (decreased) significantly (P <
      0.05), with the subject mean total WOMAC score decreasing from 25.4 +/- 2.4 to
      17.4 +/- 2.1 (~31%), pre- to post-intervention. No clinical measure was
      significantly impacted by use of CQ supplementation. CONCLUSION: An 8-week course
      of supplementation with CQ reduced joint pain in a sample of 29 young, otherwise
      healthy, exercise-trained men. Additional study is needed to extend these
      findings, including comparison with a placebo-controlled cohort, and possibly,
      examining effects of CQ use in women and older adult subjects.

PMID- 24113701
TI  - Tendinopathy: a review of the pathophysiology and evidence for treatment.
AB  - The understanding of tendinopathy has evolved over the past several decades.
      Initially thought to be a primarily inflammatory process, histologic evaluation
      has revealed that there is an absence of inflammatory cells, and rather,
      tendinopathy is more of a degenerative process. Various types of medications,
      rehabilitation, modalities, injections, and minimally invasive procedures have
      been described as treatment for this condition. The purpose of our article is to
      describe the pathophysiology of tendinopathy as currently understood and the
      evidence for the various available treatments. We performed a literature search
      to determine the types of reviews that have been performed previously regarding
      treatment for tendinopathy, and summarized these reviews. We then performed a
      systematic review of randomized controlled trials for treating patients with
      tendinopathy. It is our hope that our review of trial data will help providers to
      determine optimal management for their patients with tendinopathy. 

PMID- 24113702
TI  - A review of guidelines and pharmacologic options for asthma treatment, with a
      focus on exercise-induced bronchoconstriction.
AB  - Asthma affects millions of individuals worldwide. Exercise-induced
      bronchoconstriction is common in patients diagnosed with asthma, but may also
      occur in patients without chronic asthma. Patients with isolated exercise-induced
      bronchoconstriction may require pretreatment with inhaled short-acting beta
      agonists prior to exercise. Patients diagnosed with asthma can achieve good
      control of the symptoms of exercise-induced bronchoconstriction with appropriate
      treatment of underlying chronic asthma. Current guidelines suggest staging
      patients with asthma based on severity of symptoms and initiating therapy
      according to their stage. Pharmacotherapy for asthma management consists of both
      quick-relief medications (short-acting beta-agonists) as well as maintenance, or
      long-term control, medications (inhaled corticosteroids, long-acting beta
      agonists, leukotriene receptor antagonists, cromolyn, and theophylline). 

PMID- 24113703
TI  - Association between cardiac dimensions and athlete lineup position: analysis
      using echocardiography in NCAA football team players.
AB  - In determining what is "abnormal"-in terms of cardiac electrical and morphologic
      remodeling in athletes-it is important to identify what is "normal" or expected.
      With specialization for each position in a football team lineup, we attempted to
      describe the association between the position played and the physiologic cardiac
      changes of designated players. We evaluated data from 85 National College
      Athletic Association football players from a single team. The participants were
      assigned to 1 of 3 groups based on position and training regimen: lineman (n =
      34), mobility/power players (n = 13), and skill players (n = 38). Players
      underwent assessment with electrocardiography and echocardiography (ECHO), with
      results interpreted by reviewers blinded to players' positions. Linemen were
      found to have greater body mass index and body surface area (BSA), as well as
      longer QRS duration (102 +/- 10 ms vs 101 +/- 7 ms in mobility/power players, and
      96 +/- 7 ms in skill players; P < 0.007). Left ventricular (LV) voltage values
      were lower in linemen (27.7 +/- 6.5 mV vs 28.8 +/- 7 mV in mobility/power
      players, and 31.8 +/- 7.6 mV in skill players; both, P < 0.05). No differences in
      ejection fraction between groups were revealed on ECHO, but ECHO did show greater
      calculated LV mass, LV end-diastolic diameter, aortic root diameter, and LV
      outflow tract diameter in linemen, whether adjusted for BSA or not, and the
      differences were statistically different. Multivariate analysis showed that
      position (P < 0.0004 and QRS duration (P = 0.03) predicted LV mass.
      Echocardiographic variables found to be associated with player position included
      LV mass adjusted for BSA (P < 0.0001), LV end-diastolic diameter adjusted for BSA
      (P < 0.0003), and QTc interval (P = 0.007). On multivariate analysis, racial
      identity did not demonstrate significant differences; however, differences
      existed on univariate analysis of electrocardiography and ECHO variables, mostly
      in skill players. In skill players, QRS duration was shorter in the African
      American (AA) subgroup compared with that in the white/other subgroup. Lateral ST
      elevation and LV end-systolic volume were greater in AA players after adjustment
      for BSA, and AA linemen had greater LV posterior wall thickness after adjustment
      for BSA. In summary, we found that football players who are linemen had greater
      heart mass than did other players, despite adjustments for body size. 

PMID- 24113704
TI  - Energy expenditure, cardiorespiratory, and perceptual responses to shallow-water
      aquatic exercise in young adult women.
AB  - INTRODUCTION: Aquatic exercise (AE) is a popular form of physical activity, yet
      few studies have assessed the individual's energy expenditure (EE) associated
      with a continuous bout of AE. Studies using indirect calorimetry to measure EE
      have reported limitations associated with test methodology and the ability to
      control individual's exercise intensity or tempo. PURPOSE: To evaluate EE and
      cardiorespiratory (CR) responses during a 40-minute shallow-water AE session in
      young adult women. METHODS: Twenty-one healthy women (aged 21.7 +/- 3.4 years)
      completed an orientation practice session and a 40-minute shallow-water AE
      session using a traditional exercise class format and the SWEAT video-based
      instructional cuing program. The high-intensity interval format included the
      following segments: 1) warm-up (3 minutes); 2) CR segment ( 22 minutes); 3)
      muscular endurance segment (ME; 10 minutes); and 4) cool-down (5 minutes).
      Subject oxygen consumption (VO2; mL/kg/min), heart rate (HR) and OMNI overall
      ratings of perceived exertion (RPE-O) were assessed each minute. Average
      kcal/min1, metabolic equivalents (METs; 1 MET = 3.5 mL/kg/min), and total kcals
      per segment and for the overall session were calculated. RESULTS: The total
      subject EE throughout the 40-minute trial (including warm-up and cool-down
      segments) was 264 kcals, with an overall average of 6.3 kcals/min (5.6 METs).The
      average kcals/min expended throughout CR segments 2 through 6 was 8.05 (7.1
      METs), with the Hoverjog segment producing the greatest average kcals/min at 8.3
      (7.3 METs). The CR portion (22 min) contributed 65% of the total EE (171 kcals)
      of the 40-minute AE trial. For the overall AE trial, the highest and average
      subject VO2 achieved were 33.3 and 19.7 mL/kg/min, respectively. The average
      highest subject heart rate achieved was 177 beats per minute (bpm), equivalent to
      90% of the participant's age-predicted HRmax. CONCLUSION: Energy expenditure
      during a 40-minute AE session met national recommendations for a daily moderate
      to-vigorous bout of physical activity offering a viable alternative to land-based
      exercise. Because AE serves as a partial-weight bearing modality, future studies
      are needed to clarify the EE of shallow-water AE in apparently healthy and
      clinical populations.

PMID- 24113705
TI  - Shoulder surgeons' perceptions of interscalene nerve blocks and a review of
      complications rates in the literature.
AB  - BACKGROUND: Interscalene nerve blocks (ISBs) have been shown to be an effective
      option for regional anesthesia in shoulder surgery. Our study presents survey
      results of shoulder surgeons' perceptions of ISBs and a literature summary of
      complications rates with ISB use. METHODS: A survey addressing demographics,
      preferences, treatment patterns, risks/benefits, and patient recommendations
      regarding the use of ISBs was created. Respondents were also asked whether they
      would elect an ISB if personally undergoing shoulder surgery, and results of
      other questions were stratified based on this personal preference. The survey was
      administered electronically to all members of the American Shoulder and Elbow
      Surgeons. A literature review of ISB-related complication rates was compiled from
      13 studies of shoulder surgery using ISB. RESULTS: Of all respondents, 58.7%
      would elect a single-shot ISB, 15.0% would elect a continuous catheter, and 26.3%
      would not elect the use of an ISB if undergoing shoulder surgery. Respondents
      from a university hospital were 1.44 times more likely to elect any ISB than
      respondents from a non-university hospital. Improved post-operative pain control
      was considered the greatest benefit, whereas persistent neuropathy was considered
      the greatest risk of ISB use. Of the respondents, 76.1% would recommend use of
      ISB to their patients undergoing shoulder surgery. Our literature review yielded
      13 applicable studies that utilized a total of 6243 ISBs, with data resulting in
      a 0.35% major complication rate and an 11.32% minor complication rate in
      patients. CONCLUSION: The majority of shoulder surgeons surveyed in our study
      would elect to have a single-shot interscalene nerve block if undergoing shoulder
      surgery themselves, indicating that ISB use is considered a safe and effective
      anesthetic option among shoulder surgeon specialists.

PMID- 24113706
TI  - Nutrition programs enhance exercise effects on body composition and resting blood
      pressure.
AB  - The purpose of our study was to examine the effects of exercise alone and
      exercise combined with specific nutrition programs on body composition and
      resting blood pressure rate. Adult participants (99 women, 22 men; aged 20-86
      years) completed a combined strength and endurance exercise program (Exercise
      Only), or in conjunction with 1 of 2 nutrition plans (Exercise/Protein;
      Exercise/Protein/Diet). The Exercise-Only group performed 1 set of 9 resistance
      machines regimens interspersed with 3 bouts of recumbent cycling (5 minutes
      each). The Exercise/Protein group performed the same exercise program as Exercise
      Only group, plus consumed 1.5 g of protein per kg of ideal body weight on a daily
      basis. The Exercise/Protein/Diet group followed an identical Exercise/Protein
      protocol along with a restricted daily caloric intake (1200-1500 cals/day for
      women; 1500-1800 cals/day for men). After 10 weeks of training, the
      Exercise/Protein group attained greater increases (P < 0.05) in lean weight and
      greater decreases (P < 0.05) in diastolic blood pressure (DBP) rate than the
      Exercise-Only group. The Exercise/Protein/Diet group experienced greater
      reductions (P < 0.05) in body weight, body mass index (BMI), percent fat, fat
      weight, waist circumference (WC), systolic blood pressure (SBP) rate, and DBP
      rate than the Exercise-Only group, as well as greater reductions (P < 0.05) in
      body weight, BMI, percent fat, fat weight, and WC than the Exercise/Protein
      group. Our findings suggest that a higher protein nutrition plan may enhance the
      effects of exercise for increasing subject lean weight and decreasing DBP rate.
      The findings further indicate that a higher protein and lower calorie nutrition
      plan may enhance the effects of exercise for decreasing subject body weight, BMI,
      percent fat, fat weight, WC, SBP rate, and DBP rate, while attaining similar
      gains in lean body mass. 

PMID- 24113707
TI  - Anterior cruciate ligament bracing: evidence in providing stability and
      preventing injury or graft re-rupture.
AB  - Ligamentous knee injuries are common and costly, both in financial terms and time
      missed from work and recreational activities. Furthermore, ligamentous injuries
      appear to predispose patients to future osteoarthritis and other morbidities.
      Therefore, prevention strategies are important in limiting the potential impact
      of these injuries. Knee braces are one of the most often prescribed devices in
      the billion-dollar orthotic industry. Despite widespread use of prophylactic and
      functional knee braces, the evidence supporting their efficacy in reducing and/or
      preventing injury remains limited. Knee braces have been shown to be more
      effective in preventing medial collateral ligament injuries than anterior
      cruciate ligament injuries in both cadaveric and clinical studies. The use of
      functional braces after anterior cruciate ligament reconstruction has been
      supported and refuted in both postoperative and long-term studies. 

PMID- 24113708
TI  - The effects of resistance exercise training on body composition and strength in
      obese prepubertal children.
AB  - OBJECTIVE: To assess the effects of resistance exercise training on body
      composition and muscular strength in obese prepubertal children. DESIGN: Study
      participants, who were between the ages of 8 and 12 years, met Tanner I (stage)
      criteria, had a body mass index >= 95th percentile for age and sex, were
      randomized to either high-repetition, moderate-intensity resistance training (n =
      12) or to the non-intervention control group (n = 7) for 12 weeks. Exercise
      training was performed twice a week for 75 minutes per session. Body composition
      was assessed using dual energy x-ray absorptiometry and muscular strength was
      evaluated using a 1-repetition-maximum test. RESULTS: Exercise-group participants
      attended 98% of the 24 total sessions and showed a significant increase in body
      weight (57.6+/- 13.5 vs 59.6+/- 14.1 kg), height (144.9+/- 9 vs 146.6+/- 10.4
      cm), lean body mass (32.6+/- 6.8 vs 34.0+/- 7.0 kg), lean body mass index (lean
      body mass in kg/height2; 15.3+/- 1.6 vs 15.6+/- 1.5 kg/m2), arm strength (28.4+/-
      5.8 vs 31.2+/- 6.0 kg), and leg strength (89.4+/- 31.7 vs 113.4+/- 34 2 kg) from
      baseline measures (P < 0.05). Control group participants also showed significant
      increases in weight, height, and lean body mass from baseline measures (P < 0.05)
      but not in arm or leg strength. When the changes in participant body composition
      and muscular strength were compared between the exercise and control groups,
      significant differences were found in leg lean mass and leg strength (P < 0.05).
      There were no changes in percent body fat and fat mass index [FM/height2(kg/m2)]
      in either group. CONCLUSION: Resistance training increases leg lean mass and leg
      strength in obese prepubertal youth and may have a positive effect on overall
      physical activity and health.

PMID- 24113709
TI  - Eminence-based medicine versus evidence-based medicine: when can the athlete with
      a sprained ankle return to play?
AB  - When can the athlete with a sprained ankle to return to play? The medical
      literature provides no definitive answer to this question, so we surveyed 500
      experts in sports medicine, and asked them if they agree with the following
      statement: "For patients with an acute ankle injury, the ability to hop on the
      sidelines is sufficient evidence to allow the athlete to return to the field."
      Overall, the experts did not endorse this statement. Further, a review of the
      medical literature failed to lend support for the statement. Taken together, some
      level V (expert opinion) evidence emerges, namely, that a patient's ability to
      successfully complete the hop test is not necessarily sufficient evidence to
      allow a return to play. That finding does not mean that a physician must shun the
      test; rather, the conclusion is that it cannot be relied on in isolation. The hop
      test, used in context with other findings, along with a consideration of the
      risks and benefits of continued play, may help the physician on the field reach a
      reasonable conclusion. To date, however, there is no single, easily applied test
      that can correctly determine whether an athlete is safe to return to the field. 

PMID- 24113710
TI  - Review of: effect of vitamin D supplementation on progression of knee pain and
      cartilage volume loss in patients with symptomatic osteoarthritis.

PMID- 24113711
TI  - Pellino3 targets RIP1 and regulates the pro-apoptotic effects of TNF-alpha.
AB  - Tumour necrosis factor-alpha (TNF) can activate NF-kappaB to induce pro
      inflammatory genes but can also stimulate the caspase cascade to promote
      apoptosis. Here we show that deficiency of the ubiquitin E3 ligase, Pellino3,
      sensitizes cells to TNF-induced apoptosis without inhibiting the NF-kappaB
      pathway. Suppressed expression of Pellino3 leads to enhanced formation of the
      death-induced signalling complex, complex II, in response to TNF. We show that
      Pellino3 targets RIP1, in a TNF-dependent manner, to inhibit TNF-induced complex
      II formation and caspase 8-mediated cleavage of RIP1 in response to
      TNF/cycloheximide co-stimulation. Pellino3-deficient mice also show increased
      sensitivity to TNF-induced apoptosis and greatly increased lethality in response
      to TNF administration. These findings define Pellino3 as a novel regulator of TNF
      signalling and an important determining factor in dictating whether TNF induces
      cell survival or death. 

PMID- 24113712
TI  - Review on measurement techniques of transport properties of nanowires.
AB  - Physical properties at the nanoscale are novel and different from those in bulk
      materials. Over the last few decades, there has been an ever growing interest in
      the fabrication of nanowire structures for a wide variety of applications
      including energy generation purposes. Nevertheless, the study of their transport
      properties, such as thermal conductivity, electrical conductivity or Seebeck
      coefficient, remains an experimental challenge. For instance, in the particular
      case of nanostructured thermoelectrics, theoretical calculations have shown that
      nanowires offer a promising way of enhancing the hitherto low efficiency of these
      materials in the conversion of temperature differences into electricity.
      Therefore, within the thermoelectrical community there has been a great
      experimental effort in the measurement of these quantities in actual nanowires.
      The measurements of these properties at the nanoscale are also of interest in
      fields other than energy, such as electrical components for microchips, field
      effect transistors, sensors, and other low scale devices. For all these
      applications, knowing the transport properties is mandatory. This review deals
      with the latest techniques developed to perform the measurement of these
      transport properties in nanowires. A thorough overview of the most important and
      modern techniques used for the characterization of different kinds of nanowires
      will be shown. 

PMID- 24113713
TI  - Factors determining the success of endovascular treatments among patients with
      spinal dural arteriovenous fistulas.
AB  - INTRODUCTION: Despite improvements of embolization agents and techniques,
      endovascular treatment of spinal dural arteriovenous fistula (SDAVF) is still
      limited by inconsistent success. The aim of embolization is to occlude initial
      portion of the draining vein by liquid embolic materials. This study investigates
      factors that contribute to the success of embolization treatments among SDAVF
      patients. METHODS: We performed a retrospective analysis on consecutive SDAVF
      patients who received N-butyl cyanoacrylate (NBCA) glue embolization between
      January 1992 and June 2012. Univariable and multivariable logistic regression
      analyses were performed to calculate the probability of successful draining vein
      occlusion for variable procedure-related factors. RESULTS: We attempted
      endovascular approach as the first intention treatment in 66 out of 90
      consecutive patients. Among them, a total of 43 NBCA glue injections were
      performed in 40 patients. Successful embolization was achieved in 24 patients (60
      %). In multivariable analyses, antegrade flow during microcatheter test injection
      (OR 13.2, 95 % CI 1.7 to 105.4) and use of glue concentration >= 30 % (OR 0.1, 95
      % CI 0.01 to 0.8) were detected as significant positive and negative predictors
      of successful venous penetration, respectively. With persistent antegrade flow,
      the success rates using a glue mixture of more than 30 % dropped significantly
      from 85.0 to 42.9 % (p = 0.049). If contrast stagnated during microcatheter
      injections, success rates were low regardless of glue concentrations.
      CONCLUSIONS: Presence of antegrade flow toward the draining vein and injection of
      NBCA glue less than 30 % are associated with higher chance of draining vein
      penetration and, therefore, successful endovascular SDAVF obliteration.

PMID- 24113714
TI  - Diffusion tensor imaging to evaluate commissural disconnection after corpus
      callosotomy.
AB  - INTRODUCTION: Corpus callosum transection can prevent propagation of epileptic
      discharges. If seizures persist after surgery, assessment of the efficacy of the
      transection requires knowledge that the commissural fibers have been disrupted.
      We evaluated whether diffusion tensor imaging (DTI) and diffusion tensor fiber
      tracking can assess the degree of callosal transection and determine which white
      matter pathways remain intact. METHODS: This HIPAA-compliant retrospective study
      was performed after Institutional Review Board approval. Patients who underwent
      corpus callosotomy with postoperative magnetic resonance imaging (MRI) that
      included DTI were identified. Axial DTI was performed with either 15 or 25
      noncollinear directions of encoding. MRI and DTI were reviewed by two board
      certified neuroradiologists to evaluate commissural disconnection. RESULTS: One
      hundred eleven patients underwent corpus callosotomy with postoperative MRI, of
      which 32 had postoperative DTI. Of these 32, there were 16 males and 16 females,
      with a mean age of 12.2 +/- 6.3 years (range 0.24 to 32.8 years, median 12.3).
      Eighteen patients had undergone complete callosal transection and 14 patients had
      partial callosal transection. Seventeen of 18 patients undergoing complete
      callosal transection had structural and diffusion tensor fiber tracking (DT-FT)
      evidence of complete transection. The forceps major was intact in all patients
      undergoing partial transection. At least some commissural fibers originating from
      the precuneus, postcentral gyrus, and posterior cingulate were intact in all six
      partial transections which spared the callosal isthmus. CONCLUSION: DTI and DT-FT
      aid in the postoperative characterization in patients with callosal transection
      for seizure control. This can confirm whether the intended fibers have been
      disconnected, helping in the planning for possible further surgical intervention
      versus other therapies.

PMID- 24113715
TI  - Trilayer-cubic core-shell structure of PbS/EuS nanocrystals revealed by the
      combination of the synchrotron small-angle X-ray scattering method and energy
      dispersive X-ray spectroscopy.
AB  - Multilayer nanostructure analysis has been carried out for core-shell PbS/EuS
      nanocrystals by the combination of the synchrotron small-angle X-ray scattering
      (SAXS) method and energy-dispersive X-ray spectroscopy (EDS). SAXS patterns of a
      dilute hexane solution of the PbS/EuS nanocrystals were measured at a high signal
      to-noise ratio by using synchrotron radiation. Initial structure models used for
      SAXS data analyses were obtained from EDS images of the particle where Eu and O
      atoms are localized only in the shell part of a quasi-cubic particle and, on the
      other hand, Pb and S atoms in the core. By simulating the intensity of SAXS using
      multilayer-cubic models with various core-shell electron density distributions,
      it was found that the particle structure was explained approximately as a
      trilayer-cubic model having the PbS core and the EuS/Eu2O3 shell. The diagonal
      length of the cubic particle was ca. 9.4 nm and the estimated thicknesses of EuS
      and Eu2O3 layers in the shell were ca. 1.9 and 2.9 nm at maximum, respectively. 

PMID- 24113716
TI  - Preparation of pharmaceutical important fluorinated 1-arylethanols using isolated
      enzymes.
AB  - Fluorinated 1-arylethanols are important building blocks in medicinal chemistry
      especially for preparing kinase inhibitors for cancer therapy, NK1 receptor
      antagonists and drugs used in treatment of osteoporosis. Asymmetric reduction of
      carbonyl groups using enzymes is one of the key technologies to obtain such
      molecules in enantiomerically pure form. By using isolated enzymes coupled with
      cofactor recycling, highly concentrated, robust and economical processes can be
      developed. The aim of this review is to give an overview of biocatalytic carbonyl
      reduction with special focus on processing of fluoro containing 1-arylethanones
      with enzymes in cell free systems. The methodologies applied to improve the
      reactions are highlighted, alongside potential application of the building blocks
      in bioactive compounds. Enzymatic ketone reduction is concluded to be most
      beneficial as compared to chemo catalytic methods in transformations of highly
      fluorinated and therefore electron deficient ketones. A high enantiomeric excess
      can be achieved, and by changing the catalyst, both enantiomers are accessible.
      High rates are often seen for such electron deficient ketones, and the reactions
      have a favourable equilibrium position. 

PMID- 24113717
TI  - Characteristics of plaque progression detected by serial coronary computed
      tomography angiography.
AB  - We previously reported that serial coronary computed tomography angiography (CTA)
      had a potential to evaluate the interval change of plaque morphology of coronary
      arteries. The aim of this study was to evaluate variables associated with the
      plaque progression by serial CTA. We included 148 patients (age 66.3 +/- 9.8
      years, male 81.1 %, median scan interval 12 months) with coronary artery disease
      undergoing serial CTA. Each coronary artery was compared visually between
      baseline and follow-up CTA to detect plaque progression. Baseline characteristics
      between progression and nonprogression patients did not demonstrate any
      significant differences. Logistic analysis revealed that only low-density
      lipoprotein cholesterol (LDL-C) >=100 mg/dl at follow-up was associated with
      plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P =
      0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0
      mg/dl based on receiver-operator characteristic curves analyses. Of the 36
      progressive lesions in 32 patients, plaque composition at baseline included 13
      lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12
      lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions
      (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up.
      There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at
      baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of
      coronary arteries by serial CTA was associated with LDL-C >=100 mg/dl at follow
      up regardless of baseline LDL-C level. There was no specific finding to predict
      plaque progression on the baseline plaque characteristics. 

PMID- 24113718
TI  - Suppression of ventricular fibrillation by electrical modification of the
      Purkinje system in hypertrophic cardiomyopathy.
AB  - A 56-year-old man in hypertrophic cardiomyopathy had an electrical storm caused
      by ventricular fibrillation (VF). Mapping during the initiation of the VF
      triggered by a premature ventricular contraction (PVC1), with right bundle branch
      block (RBBB)-like morphology and superior axis, demonstrated a prominent Purkinje
      muscle junction (PMJ) delay at the distal portion of the left posterior fascicle.
      Delivery of radiofrequency (RF) energy to this area abolished the VF triggered by
      the PVC1. However, VF emerged by triggering another PVC (PVC2) with RBBB-like
      morphology and inferior axis. Similarly, the initiation of VF was associated with
      the PMJ delay at the peripheral left anterior fascicle, where RF delivery
      completely suppressed the VF. The PMJ delay and subsequent Purkinje-muscle
      reentry-like activity could be essential for the initiation of the Purkinje
      related VF.

PMID- 24113720
TI  - Graphene-based charge sensors.
AB  - We discuss graphene nanoribbon-based charge sensors and focus on their
      functionality in the presence of external magnetic fields and high frequency
      pulses applied to a nearby gate electrode. The charge detectors work well with in
      plane magnetic fields of up to 7 T and pulse frequencies of up to 20 MHz. By
      analyzing the step height in the charge detector's current at individual charging
      events in a nearby quantum dot, we determine the ideal operation conditions with
      respect to the applied charge detector bias. Average charge sensitivities of 1.3
      * 10(-3)e Hz(-1/2) can be achieved. Additionally, we investigate the back action
      of the charge detector current on the quantum transport through a nearby quantum
      dot. By varying the charge detector bias from 0 to 4.5 mV, we can increase the
      Coulomb peak currents measured at the quantum dot by a factor of around 400.
      Furthermore, we can completely lift the Coulomb blockade in the quantum dot.

PMID- 24113719
TI  - In planta protein interactions of three alphacryptoviruses and three
      betacryptoviruses from White Clover, Red Clover and Dill by bimolecular
      fluorescence complementation analysis.
AB  - Plant-infecting viruses of the genera Alpha- and Betacryptovirus within the
      family Partitiviridae cause no visible effects on their hosts and are only
      transmitted by cell division and through gametes. The bipartite dsRNA genome is
      encoding a RNA-dependent RNA polymerase (RdRp) and a coat protein (CP). Aside
      from sequence and structural analysis, the investigation of protein interactions
      is another step towards virus characterization. Therefore, ORFs of two type
      members White Clover Cryptic Virus 1 and 2 (WCCV-1 and WCCV-2), as well as the
      related viruses from Red Clover and Dill were introduced into a bimolecular
      fluorescence complementation assay. We showed CP-CP dimerization for all tested
      viruses with localization for alphacryptoviruses at the nuclear membrane and for
      betacryptoviruses close to cell walls within the cytoplasm. For CPs of WCCV-1 and
      WCCV-2, deletion mutants were created to determine internal interaction sites.
      Moreover, RdRp self-interaction was found for all viruses, whereas CP-RdRp
      interactions were only detectable for the alphacryptoviruses. An intra-genus test
      of CPs was successful in various virus combinations, whereas an inter-genus
      interaction of WCCV-1CP and WCCV-2CP was absent. This is the first report of in
      vivo protein interactions of members in the family Partitiviridae, indicating
      distinct features of the alpha- and betacryptoviruses. 

PMID- 24113721
TI  - Use of Facebook as a teaching tool in a veterinary communications course.
AB  - First-year veterinary students enrolled in a Professional Development course were
      invited to join a Facebook group with the goal of having the instructor use that
      tool to promote student practice of client communication skills. All members of
      the class were surveyed to determine any difference in educational outcomes
      between those students who joined the Facebook group (FB) and those who did not
      (non-FB). Fifty-one students joined the Facebook group out of a class of 99, and
      33 responded to the survey. Forty-four of the non-FB students completed the
      survey, for a total response of 77%. There was no difference between groups in
      their general use of Facebook. The only educational outcome that differed between
      the groups was increased practice of communication skills outside of school by
      the FB group. Students in the FB group cited interest and desire to access all
      course materials as the most common reason for joining. They were much more
      likely to read postings than to post anything themselves. Barriers to greater use
      of the tool by the FB group included lack of time and hesitance to post when
      others were not. Students were ambivalent about the use of Facebook as an
      educational tool. The instructor was unaware of the extent of use of the tool
      until survey results were gathered and felt that it would be most useful as a
      teaching tool for those instructors who already used Facebook as part of their
      personal routine. 

PMID- 24113722
TI  - Service learning: Priority 4 Paws mobile surgical service for shelter animals.
AB  - The increasing attention given to competencies needed to enter the workforce has
      revealed a need for veterinary students to gain more experience in performing
      small-animal elective surgery before graduation. In addition, guidelines for
      standards of care for shelter animals recommend that all dogs and cats should be
      spayed or neutered before adoption. Teaching surgical skills while serving the
      needs of local animal shelters represents an ideal service-learning opportunity.
      Following a pilot study and the benchmarking of other programs, an elective
      course in shelter medicine and surgery was created at Purdue University College
      of Veterinary Medicine (PVM) to allow senior DVM students an opportunity to spend
      2 weeks on a mobile surgery unit (Priority 4 Paws) and 1 week at an animal
      shelter. With financial assistance from sponsors and donors, PVM purchased and
      equipped a mobile surgery unit, hired a full-time veterinarian and a registered
      veterinary technician, and established relationships with 12 animal shelters.
      From July 30, 2012, to March 22, 2013, 1,941 spays and neuters were performed
      with excellent postsurgical outcomes while training 33 veterinary students on
      rotation and 26 veterinary technician students. The program was well accepted by
      both students and the shelters being served. The Priority 4 Paws program is an
      example of an integrated, community-based service-learning opportunity that not
      only helps to improve the surgical skills of veterinary students but also helps
      to meet an identified community need. 

PMID- 24113723
TI  - Frequency of interactions between veterinarians and other professionals to guide
      interprofessional education.
AB  - The objective of this study was to determine the frequency with which
      veterinarians interact with individuals in other health professions and related
      fields of work. Four thousand members of the American Veterinary Medical
      Association (AVMA) were surveyed. Demographic information was collected, and
      participants were asked how frequently they interacted with members of various
      professions. General comments were solicited regarding which professions
      veterinarians should reach out to in order to enhance veterinary health care and
      which professions veterinarians could interact with to improve human health care.
      The overall response rate was 18.6%. Demographic information suggested that the
      sample was representative of the profession. Frequency of interactions ranged
      from never to regularly, but for no group or profession was frequent interaction
      the norm. For practitioners, interactions with pharmacists, both dispensing and
      compounding, and with drug company representatives were most common. For
      educators, interaction with pharmacists and drug company representatives was also
      high compared to other professions, and they were also more likely to interact
      with laboratory technicians and physicians. For those in industry, interactions
      with laboratory technicians, physicians, drug and food company representatives,
      and public health officials were most common. All other respondents described
      their most common interactions as being with public health officials. The
      veterinarians surveyed cited a need for greater interaction with physicians
      regarding zoonotic disease and parasitism. Veterinarians do not frequently
      interface with human health care professionals. Those with whom practitioners
      have the greatest interaction are pharmacists and representatives of drug
      companies. Greater interaction may benefit management of zoonotic disease and
      parasitism. 

PMID- 24113724
TI  - Using authentic client interactions in communication skills training: predictors
      of proficiency.
AB  - Communication training has become a focus of concern in recent years in
      veterinary medicine. Existing literature to date indicates that Colleges of
      Veterinary Medicine (CVMs) have implemented various communication training
      protocols. The present study focused on the evaluation of a communication
      training protocol implemented in 2007 at Kansas State University (KSU) in a
      sample of veterinary medical students (N=415) across five cohorts. The protocol
      includes video review of authentic client interactions, feedback from authentic
      clients, and small-group communication training. Findings indicate that targeted
      communication skills improved through video-review feedback and small-group
      communication training. Communication scores were particularly affected by
      students' attention to improving communication deficiencies during a second
      student-client video. Baseline scores from the first student-client video in four
      specific areas (using nonverbal communication, setting expectations, building
      rapport, and being able to clarify) were predictive of overall performance during
      the second evaluation. Based on the results of the present study, using videos of
      authentic client interactions is recommended as a valuable communication training
      teaching tool. 

PMID- 24113725
TI  - Impact of fatigue on health-related quality of life in patients with Parkinson's
      disease: a prospective study.
AB  - OBJECTIVE: To investigate the longitudinal association between the impact of
      fatigue and health-related quality of life and to determine if potential
      confounders distorted this association. DESIGN: Baseline, 3-, 6- and 12-week
      assessments of a randomized clinical trial were used. SETTING: Outpatient
      rehabilitation centre. SUBJECTS: Patients with idiopathic Parkinson's disease.
      METHODS: Quality of life was assessed with the Parkinson's Disease Questionnaire
      39 and the Multidimensional Fatigue Inventory was used to assess fatigue. Time
      independent and time-dependent factors were investigated for their bivariate
      association with quality of life by applying random coefficient analysis.
      Candidate confounders were successively added to the longitudinal association
      model to determine if the relationship between quality of life and fatigue was
      distorted. A change beyond 15% of found regression coefficient of the
      Multidimensional Fatigue Inventory was considered significant. RESULTS: One
      hundred and fifty-three patients were included. Impact of fatigue was
      significantly associated with poorer quality of life (beta = 0.24, 95% confidence
      interval = 0.18 to 0.30). This association was significantly distorted by
      depression (30.0%) and anxiety (24.1%). No distortion was found for other
      factors. After controlling for confounders, fatigue remained significantly
      associated with quality of life (beta = 0.12, 95% confidence interval = 0.06 to
      0.18, r (2) = 2.3%). CONCLUSIONS: Our results suggest that patients who
      experience fatigue tend to report lower levels of quality of life. However, this
      longitudinal relationship is confounded by depression and anxiety and suggests
      that the unique contribution of fatigue to overall quality of life is rather
      small.

PMID- 24113726
TI  - Assessment of the internal construct validity of the revised High-Level Mobility
      Assessment Tool for traumatic orthopaedic injuries.
AB  - OBJECTIVE: To determine whether the revised High-Level Mobility Assessment Tool
      (HiMAT) was valid for measuring mobility for people with multi-trauma orthopaedic
      lower limb injuries. DESIGN: Cross-sectional study. SUBJECTS: Participants with
      lower limb multi-trauma orthopaedic injuries. METHODS: One complete revised HiMAT
      was obtained for 106 people within 12 weeks of being allowed to fully weight
      bear. Rasch analysis was used to assess the overall fit of the model for
      individuals and items, differential item functioning, local dependency, targeting
      of items and dimensionality. RESULTS: The mean revised HiMAT score was 10.5 (SD =
      6.8) with a range of 5-30. Rasch analysis of revised HiMAT showed adequate
      overall fit to the model (P = 0.29) with no misfitting items (fit residual SD =
      0.69) or persons (fit residual SD = 0.62). The scale showed good internal
      consistency (Person Separation Index = 0.91). One item (hopping) demonstrated
      disordered thresholds, however this item had good fit to the model in all other
      aspects. The revised HiMAT was unidimensional, and no differential item
      functioning was detected for gender or age. The revised HiMAT was well targeted
      for this group with a range of items across all ability levels. CONCLUSION: The
      results of this study support the internal construct validity of the revised
      HiMAT as a well-targeted, unidimensional measure of high-level mobility with no
      ceiling or floor effect for males and females recovering from multi-trauma
      orthopaedic lower limb injuries.

PMID- 24113727
TI  - Developing complex interventions: lessons learned from a pilot study examining
      strategy training in acute stroke rehabilitation.
AB  - OBJECTIVE: To examine the feasibility of a strategy training clinical trial in a
      small group of adults with stroke-related cognitive impairments in inpatient
      rehabilitation, and to explore the impact of strategy training on disability.
      DESIGN: Non-randomized two-group intervention pilot study. SETTING: Two inpatient
      rehabilitation units within an academic health centre. PARTICIPANTS: Individuals
      with a primary diagnosis of acute stroke, who were admitted to inpatient
      rehabilitation and demonstrated cognitive impairments were included. Individuals
      with severe aphasia; dementia; major depressive disorder, bipolar, or psychotic
      disorder; recent drug or alcohol abuse; and anticipated length of stay less than
      five days were excluded. INTERVENTION: Participants received strategy training or
      an attention control session in addition to usual rehabilitation care. Sessions
      in both groups were 30-40 minutes daily, five days per week, for the duration of
      inpatient rehabilitation. MAIN OUTCOME MEASURES: We assessed feasibility through
      participants' recruitment and retention; research intervention session number and
      duration; participants' comprehension and engagement; intervention fidelity; and
      participants' satisfaction. We assessed disability at study admission, inpatient
      rehabilitation discharge, 3 and 6 months using the Functional Independence
      Measure. RESULTS: Participants in both groups (5 per group) received the assigned
      intervention (>92% planned sessions; >94% fidelity) and completed follow-up
      testing. Strategy training participants in this small sample demonstrated
      significantly less disability at six months (M (SE) = 117 (3)) than attention
      control participants (M(SE) = 96 (14); t 8 = 7.87, P = 0.02). CONCLUSIONS: It is
      feasible and acceptable to administer both intervention protocols as an adjunct
      to acute inpatient rehabilitation, and strategy training shows promise for
      reducing disability.

PMID- 24113728
TI  - Do children participate in the activities they prefer? A comparison of children
      and youth with and without physical disabilities.
AB  - OBJECTIVE: To assess the discrepancy between the leisure activities children
      prefer and the leisure activities they actually participate in, for children with
      and without a physical disability, and to explore how in both groups this is
      related to age and gender. DESIGN: Cross-sectional comparison. SUBJECTS: Children
      with and without physical disabilities that were recruited from schools for
      special education and regular schools in the Netherlands. MAIN MEASURES: The
      Children's Assessment of Participation and Enjoyment (CAPE) and the Preferences
      for Activities of Children (PAC). A discrepancy score was calculated representing
      high preference but no participation in the activity in the past four months.
      RESULTS: A total of 141 children (6-18 years) with a physical disability (mean
      age 12.5, 43% girls, 57% boys) and 156 children without physical disabilities
      (mean age 11.5, 55% girls,45% boys) were included in the study. There was no
      significant difference in discrepancy scores between children with and without
      physical disabilities (informal activities 9.8 +/- 5.0 vs. 9.8 +/- 4.6, formal
      activities 6.4 +/- 3.4 vs. 6.6 +/- 2.8). Discrepancy between preference and
      performance varied by age and gender for children without disabilities but not
      for children with disabilities. CONCLUSIONS: Both groups are equally able to
      participate in the activities they prefer. Age and gender had a significant
      effect on the discrepancy scores for children and adolescents without physical
      disabilities but not for children with physical disabilities.

PMID- 24113729
TI  - The expression and clinical significance of PA28 gamma in colorectal cancer.
AB  - OBJECTIVE: The aims of this study were to detect differences in PA28 gamma
      expression between healthy colorectal, colorectal adenoma, and colorectal cancer
      (CRC) tissues and to explore the significance of PA28 gamma in the development of
      CRC. METHODS: Western blotting was used to assay the PA28 gamma expression
      protein in the healthy colorectal and the CRC tissue. Tissue array was used to
      assay the PA28 gamma expression in the healthy colorectal, colorectal adenoma,
      and CRC tissues. Follow-up was performed in the patients with CRC, and survival
      analysis was used to assay the correlation between PA28 gamma and the survival
      time after surgical resections. RESULTS: The Western blotting results revealed
      that the PA28 gamma expression was higher in the CRC tissue than in the healthy
      colorectum. Tissue array showed that PA28 gamma was low in the healthy
      colorectum, higher in the colorectal adenoma, and highest in the CRC tissue. The
      expression of PA28 gamma correlated with differentiation and TNM stage of the CRC
      tissue. However, there was no significant difference in the PA28 gamma expression
      between CRC and rectal cancer. No significant difference was found in survival
      rate between PA28 positive staining and PA28 negative staining. The Cox
      proportional hazard model showed that the survival time correlated with only the
      differentiation degree of CRC. CONCLUSIONS: PA28 gamma was involved in the early
      events of CRC. It contributes to the carcinogenesis and progression of CRC and
      may be a biomarker for the early diagnosis of CRC.

PMID- 24113730
TI  - Ultrasound assessment for the rapid classification of early arthritis patients.
AB  - OBJECTIVE: The present study aimed to assess the role of ultrasound (US) in the
      rapid classification of early rheumatoid arthritis (RA) by investigating whether
      the US features of inflammation and bone damage in early arthritis overlap with
      the actual clinical concept of classifying and identifying an aggressive disease.
      METHODS: Patients with recent-onset arthritis of at least 1 peripheral joint of
      the hands and/or the feet were consecutively included in this study. Clinical
      examination, laboratory tests, the Disease Activity Score 28 (DAS28), and the
      2010 American College of Rheumatology/European League Against Rheumatism
      (ACR/EULAR) classification criteria for RA were assessed for all patients.
      Medication with disease-modifying antirheumatic drugs was recorded. Ultrasound
      assessment was performed at the following anatomical sites: wrists,
      metacarpophalangeal joints 2 to 5, and metatarsophalangeal joints 2 to 5 for
      assessing the presence/absence of synovial hypertrophy, the presence/absence of
      power Doppler signal, and the presence/absence of bone erosions.The US features
      of inflammation and bone damage were analyzed in comparison with the DAS28, with
      the presence/absence of rheumatoid factor and anti-cyclic citrullinated peptide,
      with the fulfillment of the new 2010 ACR/EULAR classification criteria, and with
      the initiated disease-modifying antirheumatic drug. The prescription of
      methotrexate was considered a marker of an aggressive disease. RESULTS: The US
      features of inflammation and bone damage correlated with the activity scores
      measured by the DAS28. The presence of US bone erosions overlapped with the
      presence of rheumatoid factor and anti-cyclic citrullinated antibodies. Synovial
      hypertrophy, intra-articular power Doppler signal, and bone erosions detected in
      at least 1 anatomical site were seen in patients fulfilling (77.7%) and in
      patients not fulfilling (72.7%) the 2010 ACR/EULAR classification criteria for
      RA. Synovial hypertrophy was found in at least 1 site in 83.3% and 58.8% of
      patients in whom methotrexate was prescribed and in whom methotrexate was not
      prescribed, respectively (P = 0.01). The US features were not correlated with the
      initiation of sulfasalazine or hydroxychloroquine. The patients presenting bone
      erosions received in significantly higher percentages the indication for
      methotrexate (50%) compared with sulfasalazine (20%), P = 0.03, or
      hydroxychloroquine (26%), P = 0.05. CONCLUSIONS: The US features of inflammation
      might be of help in classifying early arthritis patients despite the presence of
      the immune markers for RA. Together with the US features of bone damage, these
      might be used as an indicator of a more aggressive disease. The absence of
      correlation between the US findings of RA and the 2010 ACR/EULAR classification
      criteria indicates a possible independent contribution of US in the understanding
      of the future evolution of these patients.

PMID- 24113731
TI  - Course of graves disease in interferon-treated patients with chronic hepatitis C
      virus infection and in uninfected patients.
AB  - BACKGROUND: The development of thyroid antibodies and the alteration of thyroid
      function are the most common disorders associated with interferon alfa therapy in
      individuals with chronic hepatitis C (CHC).In this study, we compared the course
      of Graves disease (GD) between patients diagnosed with CHC and treated with
      interferon alfa and uninfected patients. METHODS: We retrospectively analyzed
      data from 39 GD patients (15 men and 24 women, group 1) affected by CHC and
      treated with interferon alfa and from 43 uninfected GD patients (19 men and 24
      women, group 2) who were seen at our institution from 1999 to 2011. All GD
      patients were treated with methimazole (MMI). Daily dose of MMI, duration of MMI
      therapy, and remission rate were evaluated in both groups. RESULTS: The daily
      dose of MMI was found to be lower in group 1 as compared with group 2 (9.74 +/-
      5.94 mg/d vs 14.12 +/- 8.64 mg/d in group 1 vs group 2, respectively, P < 0.01).
      In addition, the duration of MMI treatment was found to be lower in group 1 as
      compared with group 2 (13.98 +/- 13.0 months vs 38.86 +/- 27.13 months in group 1
      vs group 2, respectively; P < 0.01). The remission rate from GD was higher in the
      patients of group 1 in comparison with the patients of group 2 (87.17 % vs 48.86%
      in group 1 vs group 2, respectively, P < 0.005). CONCLUSION: Altogether, our data
      demonstrate a more favorable course of GD in the patients with CHC treated with
      interferon alfa compared with GD occurring in the patients without CHC.

PMID- 24113732
TI  - Clinical judgment does not circumvent the need for diagnostic endoscopy in upper
      gastrointestinal hemorrhage.
AB  - BACKGROUND: To better understand the ability of physicians to predict the need
      for endoscopic therapy and to accurately predict specific endoscopic lesions, we
      performed a prospective, nonrandomized, observational cohort study in patients
      presenting with upper gastrointestinal hemorrhage (UGIH) who were undergoing
      endoscopy. AIM: We aimed to evaluate the pre-endoscopy diagnostic accuracy and
      the correct prediction of high-risk lesions in patients with UGIH according to
      the level of clinical expertise. METHODS: One hundred twenty-one patients
      presenting with hematemesis and/or melena within 48 hours were studied. A
      questionnaire was given to primary physicians, gastroenterology fellows, and
      gastroenterology faculty, asking them to predict the need for endoscopic therapy
      and the cause of the bleed. RESULTS: The need for endoscopic therapy was
      predicted accurately by 68% of the primary physicians, 70% of the fellows, and
      74% of the faculty physicians (P = 0.61). The faculty were able to predict which
      patients did not need therapy more accurately than the fellows and the residents:
      85%, 78%, and 68%, respectively (P = 0.03). The diagnostic accuracy of the
      clinicians--that is, the ability to accurately predict the bleeding lesion among
      the primary physicians, fellows, and faculty physicians, was similar at 46%, 52%,
      and 48%, respectively (P = 0.65). CONCLUSIONS: The accuracy of predicting the
      need for endoscopic therapy and the culprit cause of UGIH, based on clinical
      evaluation, was similar across levels of expertise. However, the faculty
      gastroenterologists were better than the gastroenterology fellows and the primary
      providers in predicting which patients do not require endoscopic treatment. We
      conclude that the relative inability of any group of physicians to accurately
      predict the presence of high-risk lesions requiring endoscopic therapy suggests
      that most patients with UGIH should undergo upper endoscopy for diagnosis and
      possible therapy.

PMID- 24113733
TI  - The effects of suplatast tosilate treatment and prophylaxis on lung
      histopathology in a mouse model of chronic asthma.
AB  - INTRODUCTION: Suplatast tosilate is a medication that inhibits TH2-type
      cytokines. We aimed to investigate the effects of suplatast tosilate treatment
      and prophylaxis on lung histopathology and cytokine levels in a mouse model of
      chronic asthma. MATERIALS AND METHODS: Forty-two BALB/c mice were divided into 6
      groups: group I (control), group II (vehicle control), group III (dexamethasone),
      group IV (prophylaxis with suplatast tosilate), group V (treatment with suplatast
      tosilate), and group VI (prophylaxis and treatment with suplatast tosilate). All
      of the groups, except for the control and vehicle control groups, were sensitized
      and challenged with ovalbumin. The mice in the study groups, except those in the
      group receiving suplatast tosilate for prophylaxis only, were treated with study
      drugs. After the mice were killed, IL-4, IL-5, and interferon-gamma levels were
      quantified in the lung tissue, which were examined histologically by light and
      electron microscopy. RESULTS: There were significant improvements in all
      histopathological parameters in the group treated with suplatast tosilate
      compared with the vehicle control group. Similar improvements were observed when
      the group receiving prophylaxis and treatment with suplatast tosilate was
      compared with the vehicle control as well. There were no significant differences
      between the group receiving only prophylaxis with suplatast tosilate and the
      vehicle control group. Cytokine levels were significantly higher in the vehicle
      control group when compared with the control group. Although all of the groups
      had lower cytokine levels than those of the vehicle control group, the
      differences were not statistically significant. CONCLUSIONS: Treatment with
      suplatast tosilate was effective in improving all histopathological parameters in
      a mouse model of chronic asthma. It was observed that the use of prophylactic
      suplatast tosilate was ineffective and had no additional effects when
      administered together with treatment.

PMID- 24113734
TI  - The effect of dietary counseling on nutrient intakes in gastric banding surgery
      patients.
AB  - BACKGROUND: There is some evidence that bariatric surgery patients who undergo
      the purely restrictive procedures, such as the gastric banding (GB) or the
      vertical banded gastroplasty surgery, do not meet the dietary reference intakes
      for several nutrients. Whether dietary counseling improves micronutrient and
      macronutrient intakes was examined in GB surgery patients. METHODS: Twenty-three
      GB surgery patients received dietary and behavioral counseling for 12 weeks to
      limit energy intake and improve nutrient intakes. Food intake was assessed by 3
      day food record at baseline and 6 and 12 weeks. Postintervention data were
      available in 21 patients. RESULTS: At baseline, more than 50% of the subjects
      reported inadequate dietary intakes of 13 nutrients but overconsumption of sodium
      and percent energy from saturated and trans-fatty acids. Mixed-effects model for
      repeated measures revealed a significant reduction in energy (P = 0.0007),
      absolute protein (P = 0.04), cholesterol (P = 0.045), and potassium (P = 0.01)
      intake and an increase in vitamin K (P = 0.03) intake and percent energy from
      protein (P = 0.005) during the 12 weeks. The McNemar test showed a reduction in
      the proportion of the subjects with an inadequate intake of vitamin K (P = 0.008)
      but an increase in the proportion of the subjects with an inadequate intake of
      thiamin (P = 0.03) at 12 weeks. The proportion of the subjects who did not meet
      the nutrient requirements for the remaining 27 nutrients was generally high and
      remained unchanged. CONCLUSIONS: Dietary intervention improved the intake of some
      nutrients in the GB surgery patients. However, most nutrient intake requirements
      remained unmet by many subjects. These results indicate that nutritional
      counseling beyond 12 weeks is warranted in GB surgery patients to improve their
      dietary nutrient intakes.

PMID- 24113735
TI  - A cut-point value of uncarboxylated to carboxylated index is associated with
      glycemic status markers in type 2 diabetes.
AB  - BACKGROUND: The uncarboxylated osteocalcin (ucOC) has been described as a
      regulator of glucose metabolism in mice, and it is decreased in human type 2
      diabetes mellitus (T2D). Although inversely correlated with serum glucose,
      insulin, and glycated hemoglobin, it is unclear if ucOC decrement is caused by
      diabetes or plays a role in the pathogenesis and/or progression of the disease.
      Whatever the case may be, diabetes affects osteoblast gene expression, and
      possibly the proportion of ucOC over carboxylated OC (cOC). The association of
      ucOC/cOC index with glycemic status markers in patients with T2D has not been
      described before. OBJECTIVE: The objective of this study was to assess the
      ucOC/cOC index and its relationship with glycemic status markers in patients with
      T2D. METHODS: The ucOC/cOC index was determined by the quotient of ucOC and cOC
      serum levels in 80 T2D patients and 160 healthy subjects. The relationship
      between the ucOC/cOC index and glycemic status markers was evaluated. RESULTS:
      The ucOC/cOC index was low and negatively correlated to fasting plasma glucose
      and homeostasis assessment-insulin resistance model in T2D patients. The odds
      ratio for T2D patients with an ucOC/cOC index below the cut-point obtained by
      receiver operating characteristic analysis was 12.64 (confidence interval, 5.75
      27.77; P < 0.001). CONCLUSIONS: A value of ucOC/cOC index less than 0.3 is
      associated with markers of poor metabolic control in patients with T2D.

PMID- 24113736
TI  - Plasma adropin levels predict endothelial dysfunction like flow-mediated
      dilatation in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: This study investigated the role of plasma adropin levels to show
      endothelial dysfunction in individuals with type 2 diabetes mellitus and to
      compare these with flow-mediated dilatation. METHODS: A total of 92 individuals
      with diagnosed type 2 diabetes mellitus were included and divided into 2 groups
      according to their brachial flow-mediated dilatation. The endothelial dysfunction
      group consisted of 46 participants with flow-mediated dilatation change of less
      than 7%, whereas 46 participants with flow-mediated dilatation change of more
      than 7% were accepted as the nonendothelial dysfunction group. Venous blood
      samples were taken from all study participants, and plasma adropin levels were
      measured using an enzyme-linked immunosorbent assay kit. RESULTS: The mean flow
      mediated dilatation values were 13.2% +/- 4.9% in the nonendothelial dysfunction
      group, and 3.5% +/- 3.4% in the endothelial dysfunction group. Mean hemoglobin
      A1c levels were significantly higher in the endothelial dysfunction group than in
      the nonendothelial dysfunction group (8.7% +/- 1.9% vs 7.9% +/- 1.6%,
      respectively; P < 0.038). Mean plasma adropin levels were 3.04 +/- 0.79 ng/mL in
      the endothelial dysfunction group and 4.67 +/- 1.43 ng/mL in the nonendothelial
      dysfunction group; P < 0.001. Plasma adropin levels showed no correlation with
      body mass index (r = -0.072, P = 0.497) but were positively correlated with flow
      mediated dilatation values (r = 0.537, P < 0.001). In the linear regression
      analysis, adropin and hemoglobin A1c were independent risk factors for
      endothelial dysfunction in individuals with type 2 diabetes mellitus. CONCLUSION:
      Adropin is a new marker for use in demonstrating endothelial dysfunction.

PMID- 24113737
TI  - Modeling thermal sensation in a Mediterranean climate-a comparison of linear and
      ordinal models.
AB  - A simple thermo-physiological model of outdoor thermal sensation adjusted with
      psychological factors is developed aiming to predict thermal sensation in
      Mediterranean climates. Microclimatic measurements simultaneously with interviews
      on personal and psychological conditions were carried out in a square, a street
      canyon and a coastal location of the greater urban area of Athens, Greece.
      Multiple linear and ordinal regression were applied in order to estimate thermal
      sensation making allowance for all the recorded parameters or specific,
      empirically selected, subsets producing so-called extensive and empirical models,
      respectively. Meteorological, thermo-physiological and overall models -
      considering psychological factors as well - were developed. Predictions were
      improved when personal and psychological factors were taken into account as
      compared to meteorological models. The model based on ordinal regression
      reproduced extreme values of thermal sensation vote more adequately than the
      linear regression one, while the empirical model produced satisfactory results in
      relation to the extensive model. The effects of adaptation and expectation on
      thermal sensation vote were introduced in the models by means of the exposure
      time, season and preference related to air temperature and irradiation. The
      assessment of thermal sensation could be a useful criterion in decision making
      regarding public health, outdoor spaces planning and tourism. 

PMID- 24113738
TI  - Quantification of climate tourism potential of Croatia based on measured data and
      regional modeling.
AB  - Tourism is one of the most important economic sectors in Croatia. The Adriatic
      coast is a popular travel destination for tourists, especially during the summer
      months. During their activities, tourists are affected by atmospheric conditions
      and therefore by weather and climate. Therefore, it is important to have reliable
      information about thermal conditions as well as their impacts on human beings.
      Here, the climate tourism potential of Croatia is presented and quantified on the
      basis of three selected stations in different climatic regions. The
      physiologically equivalent temperature is used for analysis as well as other
      climatic parameters relevant for tourism and recreation. The results already
      point to hot conditions for outdoor activities in summer during afternoons,
      especially along the coast but also for continental regions, resulting in a
      reduction of the climate tourism potential. In the future, this trend looks set
      to increase, possibly leading to a changing tourism sector in Croatia requiring
      adaptation and new strategies. 

PMID- 24113739
TI  - Dissecting the salt dependence of the Tus-Ter protein-DNA complexes by high
      throughput differential scanning fluorimetry of a GFP-tagged Tus.
AB  - The analysis of the salt dependence of protein-DNA complexes provides useful
      information about the non-specific electrostatic and sequence-specific parameters
      driving complex formation and stability. The differential scanning fluorimetry of
      GFP-tagged protein (DSF-GTP) assay has been geared with an automatic Tm peak
      recognition system and was applied for the high-throughput (HT) determination of
      salt-induced effects on the GFP-tagged DNA replication protein Tus in complex
      with various Ter and Ter-lock sequences. The system was designed to generate two
      dimensional heat map profiles of Tus-GFP protein stability allowing for a
      comparative study of the effect of eight increasing salt concentrations on ten
      different Ter DNA species at once. The data obtained with the new HT DSF-GTP
      allowed precise dissection of the non-specific electrostatic and sequence
      specific parameters driving Tus-Ter and Tus-Ter-lock complex formation and
      stability. The major factor increasing the thermal resistance of Tus-Ter-lock
      complexes in high-salt is the formation of the TT-lock, e.g. a 10-fold higher
      Kspe was obtained for Tus-GFP:Ter-lockB than for Tus-GFP:TerB. It is anticipated
      that the system can be easily adapted for the study of other protein-DNA
      complexes. 

PMID- 24113740
TI  - Citric acid modulated electrochemical synthesis and photocatalytic behavior of
      BiOCl nanoplates with exposed {001} facets.
AB  - Well-crystallized BiOCl nanoplates with exposed {001} facets were synthesized by
      a facile electrochemical anodic oxidation method. The thickness of the nanoplates
      decreases with increasing citric acid content in the electrolyte. The optical
      absorption edge of the BiOCl nanoplates shifts to a longer wavelength with citric
      acid. The BiOCl nanoplates obtained with citric acid show a high photocatalytic
      activity for degrading rhodamine B (RhB) as compared with that without citric
      acid. The photocatalytic activity of BiOCl nanoplates is higher in degrading RhB
      dyes than in degrading rhodamine 6G, methyl orange and methyl blue dyes. The
      superoxide radical and holes are the two major active species in photocatalytic
      degradation of RhB by BiOCl nanoplates. Citric acid can decrease the overlap in
      the layered structure of BiOCl and reduce the nanoplates thickness, leading to
      the increase in the exposure of {001} facets and the enhanced photocatalytic
      activity. 

PMID- 24113741
TI  - Tale taming radioactive fears: Linking nuclear waste disposal to the "continuum
      of the good".
AB  - We examine how the constructor of the world's first repository for the final
      disposal of spent nuclear fuel in Eurajoki, Finland, aims to shape lay
      understanding of the facility's risks and to tame the nuclear fears of the local
      community by producing positive associations, imagery and tales. Our empirical
      material consists of the constructor's newsletters targeted mainly at the local
      residents. In the narrative analysis, we identified a storyline where the
      construction of the repository is linked into the "continuum of the good" in the
      municipality of the construction site and the surrounding areas. The storyline
      consists of five different themes all emphasizing the "continuum of the good" in
      the area: cultural heritage, well-being, developing expertise, natural
      environment, and local families. Our study contributes to the literature on pro
      nuclear storytelling by showing how the inclination is towards narratives that
      are constructed around local symbols, cultural landmarks, and institutions. 

PMID- 24113742
TI  - The Aeolus project: Science outreach through art.
AB  - With a general decline in people's choosing to pursue science and engineering
      degrees there has never been a greater need to raise the awareness of lesser
      known fields such as acoustics. Given this context, a large-scale public
      engagement project, the 'Aeolus project', was created to raise awareness of
      acoustics science through a major collaboration between an acclaimed artist and
      acoustics researchers. It centred on touring the large singing sculpture Aeolus
      during 2011/12, though the project also included an extensive outreach programme
      of talks, exhibitions, community workshops and resources for schools. Described
      here are the motivations behind the project and the artwork itself, the ways in
      which scientists and an artist collaborated, and the public engagement activities
      designed as part of the project. Evaluation results suggest that the project
      achieved its goal of inspiring interest in the discipline of acoustics through
      the exploration of an other-worldly work of art.

PMID- 24113743
TI  - Do alternative methods of measuring tumor size, including consideration of
      multicentric/multifocal disease, enhance prognostic information beyond TNM
      staging in women with early stage breast cancer: an analysis of the NCIC CTG MA.5
      and MA.12 clinical trials.
AB  - The AJCC staging criteria consider tumor size to be the largest dimension of
      largest tumor. Some case series suggest using summation of all tumor dimensions
      in patients with multicentric/multifocal (MC/MF) disease. We used data from NCIC
      CTG MA.5 and MA.12 clinical trials to examine alternative methods of assessing
      tumor size on breast-cancer-free-interval (BCFI). The 710 MA.5 pre-/peri
      menopausal node positive and 672 MA.12 pre-menopausal node-negative/-positive
      patients have 10-year median follow-up. All patients received adjuvant
      chemotherapy. Tumors were centrally reviewed for grade, hormone receptor, and
      HER2 status. Continuous pathologic tumor size was: (1) largest dimension of
      largest tumor (cm); (2) tumor area (cm(2)); (3) volume of tumor (cm(3)); (4) with
      MC/MF disease, summation of (1)-(3) for up to 3 foci. We examined univariate and
      multivariate effects of tumor size on BCFI utilizing (un)stratified Cox
      regression and the Wald test statistic. In univariate analysis, larger tumor
      dimension was significantly associated with worse BFCI in node positive patients:
      p < 0.0001 for MA.5; p = 0.01 for MA.12. In MA.5 multivariate analysis, larger
      summation of largest tumor dimensions was associated with worse BCFI (p =
      0.0003), while larger single dimension was associated with worse BCFI (p = 0.02)
      for MA.12. Presence of MC/MF and other tumor size measurements were not
      associated (p > 0.05) with BFCI. While physicians could consider the largest
      diameter of the largest focus of disease or the sum of the largest diameters of
      all foci in their T-stage determination, it appears that the current method of T
      staging offers equivalent determinations of prognosis.

PMID- 24113744
TI  - Prospective clinical experience with research biopsies in breast cancer patients.
AB  - There are ethical concerns regarding the performance of biopsies in patients for
      research purposes. We examined our single-institution experience regarding
      acceptance, safety, and success rate with research biopsies in patients with
      breast cancer. Among patients with data from paired samples, receptor status
      agreement between primary and metastatic samples was examined, either on first
      recurrence or after progression on one or more lines of therapy. An IRB-approved
      prospective study at the Dana-Farber Cancer Institute collects research biopsies
      as additional passes at the time of a clinical biopsy (AB, additional biopsy) or
      as a separate procedure for banking purposes (RPOB, research purposes only
      biopsy). Biopsies are not linked to a specific therapeutic or correlative trial.
      Grade 2-5 adverse events are prospectively collected. 151 patients were included
      in the analytic cohort (total procedures = 161); 80.8 % underwent AB, 17.2 %
      underwent RPOB, and 2.0 % underwent both AB and RPOB. Most patients were white
      (88.7 %) with a performance status of 0-1 (94.0 %). 96.0 % of patients underwent
      a biopsy in the setting of known or suspected metastatic disease. Receptor status
      between primary cancer and recurrent research biopsies differed in 43.2 % of
      patients with available data (18.8 % among patients who underwent the research
      biopsy before any systemic treatment, 48.1 % after treatment). Tissue was
      successfully collected in 92.3 % of patients undergoing AB and 100 % patients
      undergoing RPOB. Only three (2.0 %) patients had adverse events >= grade-2: one
      grade-2 pain; one grade-2 pneumothorax; and one grade-3 pain. Our experience
      suggests research biopsies can be performed safely with a high rate of successful
      tissue collection. Consistent with previous reports we found a high rate of
      discordance between primary and metastatic samples, which was even higher among
      treated patients. This supports continued efforts to study tissue samples at
      multiple points in a patient's disease course.

PMID- 24113746
TI  - Tunable fiber Bragg grating based on responsive photonic crystals.
AB  - A tunable fiber Bragg grating (FBG) was developed by using stress-responsive
      colloidal crystals. In addition, the FBGs with the function of dynamically
      filtering multiple wavelengths were also demonstrated by incorporating multiple
      colloidal crystal segments into the fibers. 

PMID- 24113745
TI  - Long-term surveillance mammography and mortality in older women with a history of
      early stage invasive breast cancer.
AB  - Annual surveillance mammograms in older long-term breast cancer survivors are
      recommended, but this recommendation is based on little evidence and with no
      guidelines on when to stop. Surveillance mammograms should decrease breast cancer
      mortality by detecting second breast cancer events at an earlier stage. We
      examined the association between surveillance mammography beyond 5 years after
      diagnosis on breast cancer-specific mortality in a cohort of women aged >= 65
      years diagnosed 1990-1994 with early stage breast cancer. Our cohort included
      women who survived disease free for >= 5 years (N = 1,235) and were followed from
      year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic
      surveillance mammograms were ascertained through medical record review. We used
      Cox proportional hazards regression stratified by follow-up year to calculate the
      association between time-varying surveillance mammography and breast cancer
      specific and other-than-breast mortality adjusting for site, stage, primary
      surgery type, age and time-varying Charlson Comorbidity Index. The majority (85
      %) of the 1,235 5-year breast cancer survivors received >= 1 surveillance
      mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women
      received >= 1 surveillance mammogram in years 10-14. A total of 120 women died of
      breast cancer and 393 women died from other causes (average follow-up 7.3 years).
      Multivariable models and lasagna plots suggested a modest reduction in breast
      cancer-specific mortality with surveillance mammogram receipt in the preceding
      year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause
      mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer
      survivors, surveillance mammography may reduce breast cancer-specific mortality
      even after 5 years of disease-free survival. Continuing surveillance mammography
      in older breast cancer survivors likely requires physician-patient discussions
      similar to those recommended for screening, taking into account comorbid
      conditions and life-expectancy.

PMID- 24113748
TI  - FK506-binding protein 12 modulates MU-opioid receptor phosphorylation and protein
      kinase C(epsilon)-dependent signaling by its direct interaction with the
      receptor.
AB  - Protein kinase C (PKC) activation plays an important role in morphine-induced MU
      opioid receptor (OPRM1) desensitization and tolerance development. It was
      recently shown that receptor phosphorylation by G protein-coupled receptor kinase
      regulates agonist-dependent selective signaling and that inefficient
      phosphorylation of OPRM1 leads to PKCepsilon activation and subsequent responses.
      Here, we demonstrate that such receptor phosphorylation and PKCepsilon activation
      can be modulated by FK506-binding protein 12 (FKBP12). Using a yeast two-hybrid
      screen, FKBP12 was identified as specifically interacting with OPRM1 at the
      Pro(353) residue. In human embryonic kidney 293 cells expressing OPRM1, the
      association of FKBP12 with OPRM1 decreased the agonist-induced receptor
      phosphorylation at Ser(375). The morphine-induced PKCepsilon activation and the
      recruitment of PKCepsilon to the OPRM1 signaling complex were attenuated both by
      FKBP12 short interfering RNA (siRNA) treatment and in cells expressing OPRM1 with
      a P353A mutation (OPRM1P353A), which leads to diminished activation of PKC
      dependent extracellular signal-regulated kinases. Meanwhile, the overexpression
      of FKBP12 enabled etorphine to activate PKCepsilon. Further analysis of the
      receptor complex demonstrated that morphine treatment enhanced the association of
      FKBP12 and calcineurin with the receptor. The blockade of the FKBP12 association
      with the receptor by the siRNA-mediated knockdown of endogenous FKBP12 or the
      mutation of Pro(353) to Ala resulted in a reduction in PKCepsilon and calcineurin
      recruitment to the receptor signaling complex. The receptor-associated
      calcineurin modulates OPRM1 phosphorylation, as demonstrated by the ability of
      the calcineurin autoinhibitory peptide to increase the receptor phosphorylation.
      Thus, the association of FKBP12 with OPRM1 attenuates the phosphorylation of the
      receptor and triggers the recruitment and activation of PKCepsilon. 

PMID- 24113749
TI  - Identification of novel functionally selective kappa-opioid receptor scaffolds.
AB  - The kappa-opioid receptor (KOR)-dynorphin system has been implicated in the
      control of affect, cognition, and motivation, and is thought to be dysregulated
      in mood and psychotic disorders, as well as in various phases of opioid
      dependence. KOR agonists exhibit analgesic effects, although the adverse effects
      produced by some KOR agonists, including sedation, dysphoria, and hallucinations,
      have limited their clinical use. Interestingly, KOR-mediated dysphoria, assessed
      in rodents as aversion, has recently been attributed to the activation of the p38
      mitogen-activated protein kinase pathway following arrestin recruitment to the
      activated KOR. Therefore, KOR-selective G protein-biased agonists, which do not
      recruit arrestin, have been proposed to be more effective analgesics, without the
      adverse effects triggered by the arrestin pathway. As an initial step toward
      identifying novel biased KOR agonists, we applied a multifaceted screening
      strategy utilizing both in silico and parallel screening approaches. We
      identified several KOR-selective ligand scaffolds with a range of signaling bias
      in vitro. The arylacetamide-based scaffold includes both G protein- and beta
      arrestin-biased ligands, while the endogenous peptides and the diterpene
      scaffolds are G protein biased. Interestingly, we found scaffold screening to be
      more successful than library screening in identifying biased ligands. Many of the
      identified functionally selective ligands are potent selective KOR agonists that
      are reported to be active in the central nervous system. They therefore represent
      excellent candidates for in vivo studies aiming at determining the behavioral
      effects mediated by specific KOR-mediated signaling cascades. 

PMID- 24113750
TI  - The antiallergic mast cell stabilizers lodoxamide and bufrolin as the first high
      and equipotent agonists of human and rat GPR35.
AB  - Lack of high potency agonists has restricted analysis of the G protein-coupled
      receptor GPR35. Moreover, marked variation in potency and/or affinity of current
      ligands between human and rodent orthologs of GPR35 has limited their productive
      use in rodent models of physiology. Based on the reported modest potency of the
      antiasthma and antiallergic ligands cromolyn disodium and nedocromil sodium, we
      identified the related compounds lodoxamide and bufrolin as high potency agonists
      of human GPR35. Unlike previously identified high potency agonists that are
      highly selective for human GPR35, both lodoxamide and bufrolin displayed
      equivalent potency at rat GPR35. Further synthetic antiallergic ligands, either
      sharing features of the standard surrogate agonist zaprinast, or with lodoxamide
      and bufrolin, were also shown to display agonism at either human or rat GPR35.
      Because both lodoxamide and bufrolin are symmetric di-acids, their potential mode
      of binding was explored via mutagenesis based on swapping between the rat and
      human ortholog nonconserved arginine residues within proximity of a key conserved
      arginine at position 3.36. Computational modeling and ligand docking predicted
      the contributions of different arginine residues, other than at 3.36, in human
      GPR35 for these two ligands and were consistent with selective loss of potency of
      either bufrolin or lodoxamide at distinct arginine mutants. The computational
      models also suggested that bufrolin and lodoxamide would display reduced potency
      at a low-frequency human GPR35 single nucleotide polymorphism. This prediction
      was confirmed experimentally. 

PMID- 24113751
TI  - [Clinical and pathological features of the best candidates for active
      surveillance-retrospective analysis of patients with radical prostatectomy].
AB  - To develop a more clinically relevant protocol and identify the best candidates
      for active surveillance (AS), we examined the pathological features of radical
      prostatectomy (RP) specimens of patients who met the Japanese AS protocol
      criteria. Of 342 patients who underwent RP between 2000 and 2010, 58 (17.0%)
      eligible for the Japanese AS protocol were retrospectively identified.
      Pathological features of biopsy specimens and RP specimens were compared to
      reveal the incidences of up-grading, up-staging and insignificant cancer. We also
      tried to identify preoperative clinical and pathological factors that accurately
      predicted the insignificant cancer in the surgical specimens. Up-grading (Gleason
      score >=7) and upstaging (>=pT3) were observed in 32 (55.2%) and 6 (10.3%)
      patients, respectively. Insignificant cancer was observed in 19 (32.8%). Dominant
      tumors were located in the peripheral zone (PZ) in 34 (58.6%) patients and in the
      transition zone (TZ) in 24 (41.4%). Multivariate analysis revealed that prostate
      specific antigen density <0.15 ng/ml/cm3 was a significant independent factor to
      predict insignificant cancer (odds ratio 6.70, p=0.036). Larger dominant tumors
      were associated more frequently with up-grading and up-staging (p=0.038 and
      p=0.021, respectively), and were more likely to be located in the TZ (P = 0.027).
      Our results suggest that the risk of up-grading and up-staging should be
      considered in patients who met the Japanese protocol. Larger dominant tumors were
      associated more frequently with up-grading and up-staging.

PMID- 24113752
TI  - [Efficacy of mirabegron, a beta3-adrenergic agonist, switched from an
      anticholinergic agent for female patients aged over 70 years].
AB  - In the present study, we investigated the efficacy of mirabegron, a beta3
      adrenergic agonist, in patients aged >70 years who did not respond to treatment
      with an anticholinergic agent. From February 2012 to May 2012, we examined 37
      patients who did not respond to treatment with an anticholinergic agent. We
      assessed the overactive bladder symptom score (OABSS), thirst, and constipation
      at baseline, as well as at 3 and 6 months from the start of drug administration.
      Theme an age of the female patients was 79.9+/-6.08 years. The OABSS indicated
      significant improvement in nocturia and urge incontinence at 3 and 6 months.
      Furthermore, mirabegron significantly relieved thirst (in 95.2% of cases) and
      constipation (in 87.5% of cases). Thus, mirabegron is considered useful for
      female patients aged >70 years who did not respond to treatment with an
      anticholinergic agent.

PMID- 24113753
TI  - [Case of renal subcapsular hematoma caused by flexible transurethral
      lithotripsy].
AB  - A 39-year-old man with macroscopic hematuria was admitted to our hospital. A
      stone, 5 mm in diameter was detected in the right ureteropelvic junction after
      abdominal computed tomography and plain abdominal radiography. We performed
      flexible transurethral lithotripsy (f-TUL) and crushed the stone and extracted
      almost all stone fragments without any complications. However, almost immediately
      after the operation, the patient began to complain about pain in the right back.
      In the results of abdominal plain computed tomography right renal subcapsular
      hematoma was detected. Because active bleeding was not observed in the results of
      enhanced computed tomography, only conservative treatment was performed. The
      patient was discharged from the hospital on day 11 of hospitalization. One month
      after the operation, plain computed tomography was performed and diminished
      subcapsular hematoma was detected. Renal subcapsular hematoma is assumed to be a
      unique complication of extracorporeal shock wave lithotripsy. This is the first
      report of a case of renal subcapsular hematoma caused by f-TUL. The onset of
      renal subcapsular hematoma following f-TUL could have been caused either because
      the laser fiber thrust into the renal lithiasis unintentionally or because the
      internal pressure of the renal pelvis increased substantially during the
      operation. 

PMID- 24113754
TI  - [Renal metastasis originating from colon cancer : a case report].
AB  - In 2008, a 65-year-old woman was referred to our department because of a right
      renal tumor detected by computed tomography (CT) that was associated with
      macroscopic hematuria. She underwent right hemicolectomy for ascending colon
      cancer in 2003, and right lower lobectomy for lung metastasis of colon cancer in
      2004. CT, magnetic resonance imaging, fluorodeoxyglucose positron emission
      tomography computed tomography and bone scintigraphy did not indicate any other
      metastatic lesion except the right renal mass ; therefore, open right nephrectomy
      was performed. Results of the histopathologic examination demonstrated renal
      metastasis of colon cancer. Although administration of chemotherapy was
      continued, the patient died of multiple metastases 8 months after the right
      nephrectomy.

PMID- 24113755
TI  - [Pre- surgical therapy with sunitinib for adrenal metastasis from renal cell
      carcinoma : a case report].
AB  - A 60-year-old woman received a right radical nephrectomy for a right renal cell
      carcinoma (8.5*5.4 cm), cT2N0M0, in August 2000. The histopathological findings
      revealed a clear cell carcinoma, pT2, grade 1, INFalpha, v (-). She was started
      on interferon alpha (sumiferon : 300 IU) because of an adrenal metastasis from
      the renal cell carcinoma in August 2008. However, the tumor gradually enlarged
      and there was a potential to infiltrate the pancreatic body-tail. Therefore, we
      began the administration of sunitinib for pre-surgical therapy in June 2010,
      because she had a good performance status, no metastasis to other organs except
      for the left adrenal gland, and the passage of eight years from the time of
      resection of the primary origin tumor. She had a good response to therapy, which
      shrank the tumor by 40% (partial response). Therefore we performed a left
      adrenalectomy in June 2011. The histopathological findings revealed a metastatic
      renal cell carcinoma. We stopped the administration of after the operation
      sunitinib after the operation. She has since preserved her quality of life
      without any recurrence for 19 months. 

PMID- 24113756
TI  - [Case of metastatic malignant melanoma of the urinary bladder].
AB  - A 54-year-old woman underwent resection of malignant melanoma of the left leg and
      inguinal lymph node metastases and subsequent radiation therapy (60 Gy) following
      three courses of dacarbazine, nimustine, vincristine and interferon-beta
      chemotherapy in January 2010. In September 2011, she was referred to our
      department with the chief complaint of asymptomatic gross hematuria. A non
      papillary bladder tumor was detected on cystoscopy and fluorodeoxyglucose (FDG)
      positron emission fomography-computed tomography revealed increased uptake of FDG
      only in the area of the bladder tumor. Melanoma cells were also found on urinary
      cytology. Our diagnosis was metastatic malignant melanoma of the bladder.
      Complete transurethral resection of the bladder tumor was performed, and
      pathological examination confirmed metastatic malignant melanoma. Metastatic
      bladder tumors constitute less than 5% of all bladder tumors. There are
      metastases in other organs at the time of diagnosis in almost all cases. In
      Japan, metastatic malignant melanoma of the urinary bladder is rare in clinical
      practice, there having been about a dozen reported cases. Solitary metastasis as
      in our case is even rarer. 

PMID- 24113757
TI  - [Case of primary malignant lymphoma of the bladder].
AB  - We report a case of primary malignant lymphoma of the bladder. An 87-year-old
      female visited our hospital for incidental bladder tumor. Cystoscopic examination
      demonstrated a non-papillary tumor over 10 mm in diameter. We performed
      transurethral resection of the bladder tumor. Histological examination showed
      malignant lymphoma, diffuse large B cell type. After further examination, it was
      diagnosed as primary malignant lymphoma of the bladder, stage IA E(Ann Arbor
      classification). We performed six courses of R-CHOP regimen (rituximab,
      cyclophosphamide, vincristine, doxorubicin, predonisolone). We did not find any
      local or distant recurrences after eight months' follow up. 

PMID- 24113758
TI  - [Case of prostate cancer associated with bisphosphonate-related osteonecrosis of
      the jaw followed by retropharyngeal abscess].
AB  - A 67-year-old man with castration-resistant prostate cancer associated with
      multiple bone metastases had been treated with zoledronic acid and docetaxel.
      Although there was no evidence of damage around the right lower jaw bone, the
      patient complained of pain in May 2011, which worsened during the next 2 weeks
      and was followed by difficulty with breathing. Computed tomographic (CT) findings
      of the cervical area showed swelling of the cervical tissue with air and
      tightening of the trachea, suggesting cellulitis caused by gas gangrene. He was
      intubated and treated with antibiotics. On the 12th hospital day, CT scan
      revealed a pharyngeal abscess and we performed a drainage operation. On the 20th
      hospital day, bone of the intraoral lower jaw was exposed, revealing that the
      infection was caused by osteonecrosis. Additional CT findings showed the abscess
      extending to the mediastinum and multiple liver metastases. Although antibiotic
      therapy was continued, the patient died of liver failure on the 61st day. 

PMID- 24113759
TI  - [Case of septic shock caused by extended spectrum beta-lactamase producing
      Escherichia coli after transrectal prostate biopsy, successfully treated by
      endotoxin adsorption therapy].
AB  - A 62-year-old man, with a family history of prostate cancer, referred to our
      hospital because of elevated prostate-specific antigen (PSA) (6.02 ng/ml). After
      prophylactic administration of antibiotics (cefotiam), transrectal needle biopsy
      of the prostate was performed. He was admitted to the hospital due to high fever
      the next evening. His blood pressure was below the shock level, and his renal
      function deteriorated progressively. Suspecting septic shock, the patient was
      treated with Meropenem, gamma-globulin, and dopamine, which were not effective.
      Then, endotoxin adsorption therapy was employed and the condition of the patient
      recovered soon after the initiation of the therapy. Extended spectrum beta 
      lactamase-producing Escherichia coli was found in his urine. Pathological
      diagnosis of the biopsy specimen was atypical glands. 

PMID- 24113760
TI  - [Primary adenocarcinoma of the seminal vesicle difficult to differentiate from
      rectal carcinoma : a case report].
AB  - A 78-year-old man with urinary retention visited our hospital in June 2011. He
      presented with intestinal bleeding one month later and was admitted immediately.
      Contrast enhancement computed tomography revealed a lobulated intrapelvic tumor
      and liver metastasis. The prostate specific antigen level was normal, but his
      carcinoembryonic antigen level was elevated. Based on these results, his tumor
      was diagnosed as rectal carcinoma. On day 26, total pelvic exenteration and
      pelvic lymph node dissection to arrest bleeding were performed. We created an
      ileal conduit for urinary diversion and performed a sigmoid colostomy. The final
      histopathological assessment confirmed that he had primary adenocarcinoma of the
      seminal vesicle. The patient received the best supportive care because he
      rejected postoperative adjuvant chemotherapy and hormonal therapy. He died three
      months postoperatively. Primary adenocarcinoma of the seminal vesicle is very
      rare. The prognosis for this carcinoma is poor.

PMID- 24113761
TI  - [Malignant mesotheliomas of the tunica vaginalis testis].
AB  - Malignant mesothelioma of the tunica vaginalis is rare, and is usually not
      diagnosed until surgery is undertaken. We report here a case in a 62-year-old man
      with malignant mesothelioma tunica vaginalis testis. He was referred to our
      hospital with a painless swelling of the left scrotal contents. There is a
      thickening of mesothelia of the tunica vaginalis with left sided hydrocele by
      ultrasonography and computed tomography scan. The tumor was resected under the
      diagnosis of testicular malignant tumor. However, the pathologist reported
      malignant mesothelioma and positive margin. He received external beam radiation
      therapy at a total dose of 44 Gy. Disease progression was not apparent 2 years
      after treatment. To our knowledge, 26 cases of malignant mesothelioma in the
      perineum or intrascrotum have been reported in Japan and this case is thought to
      be the 27th case in Japan. 

PMID- 24113762
TI  - Congenital megacaruncle: a unique and innocent ocular adnexal anomaly.

PMID- 24113763
TI  - Neuro-ophthalmologic features of chordoid glioma.
AB  - Chordoid glioma is a rare intracranial tumor typically arising in the third
      ventricle, particularly along the anterior aspect of the hypothalamic wall. We
      describe the clinical, neuroimaging, and pathologic factors of this neoplasm in a
      patient presenting with a chiasmal syndrome.

PMID- 24113764
TI  - For whom does it work? moderators of outcome on the effect of a transdiagnostic
      internet-based maintenance treatment after inpatient psychotherapy: randomized
      controlled trial.
AB  - BACKGROUND: Recent studies provide evidence for the effectiveness of Internet
      based maintenance treatments for mental disorders. However, it is still unclear
      which participants might or might not profit from this particular kind of
      treatment delivery. OBJECTIVE: The study aimed to identify moderators of
      treatment outcome in a transdiagnostic Internet-based maintenance treatment
      (TIMT) offered to patients after inpatient psychotherapy for mental disorders in
      routine care. METHODS: Using data from a randomized controlled trial (N=400)
      designed to test the effectiveness of TIMT, we performed secondary analyses to
      identify factors moderating the effects of TIMT (intervention) when compared with
      those of a treatment-as-usual control condition. TIMT involved an online self
      management module, asynchronous patient-therapist communication, a peer support
      group, and online-based progress monitoring. Participants in the control
      condition had unstructured access to outpatient psychotherapy, standardized
      outpatient face-to-face continuation treatment, and psychotropic management. Self
      reports of psychopathological symptoms and potential moderators were assessed at
      the start of inpatient treatment (T1), at discharge from inpatient
      treatment/start of TIMT (T2), and at 3-month (T3) and 12-month follow-up (T4).
      RESULTS: Education level, positive outcome expectations, and diagnoses
      significantly moderated intervention versus control differences regarding changes
      in outcomes between T2 and T3. Only education level moderated change differences
      between T2 and T4. The effectiveness of the intervention (vs control) was more
      pronounced among participants with a low (vs high) education level (T2-T3: B=
      0.32, SE 0.16, P=.049; T2-T4: B=-0.42, SE 0.21, P=.049), participants with high
      (vs low) positive outcome expectations (T2-T3: B=-0.12, SE 0.05, P=.02) and
      participants with anxiety disorder (vs mood disorder) (T2-T3: B=-0.43, SE 0.21,
      P=.04). Simple slope analyses revealed that despite some subgroups benefiting
      less from the intervention than others, all subgroups still benefited
      significantly. CONCLUSIONS: This transdiagnostic Internet-based maintenance
      treatment might be suitable for a wide range of participants differing in various
      clinical, motivational, and demographic characteristics. The treatment is
      especially effective for participants with low education levels. These findings
      may generalize to other Internet-based maintenance treatments.

PMID- 24113765
TI  - ALOHA: a novel probability fusion approach for scoring multi-parameter drug
      likeness during the lead optimization stage of drug discovery.
AB  - Automated lead optimization helper application (ALOHA) is a novel fitness scoring
      approach for small molecule lead optimization. ALOHA employs a series of
      generalized Bayesian models trained from public and proprietary pharmacokinetic,
      absorption, distribution, metabolism, and excretion, and toxicology data to
      determine regions of chemical space that are likely to have excellent drug-like
      properties. The input to ALOHA is a list of molecules, and the output is a set of
      individual probabilities as well as an overall probability that each of the
      molecules will pass a panel of user selected assays. In addition to providing a
      summary of how and when to apply ALOHA, this paper will discuss the validation of
      ALOHA's Bayesian models and probability fusion approach. Most notably, ALOHA is
      demonstrated to discriminate between members of the same chemical series with
      strong statistical significance, suggesting that ALOHA can be used effectively to
      select compound candidates for synthesis and progression at the lead optimization
      stage of drug discovery. 

PMID- 24113766
TI  - Peristalsis and propulsion of colonic content can occur after blockade of major
      neuroneuronal and neuromuscular transmitters in isolated guinea pig colon.
AB  - We recently identified hexamethonium-resistant peristalsis in the guinea pig
      colon. We showed that, following acute blockade of nicotinic receptors,
      peristalsis recovers, leading to normal propagation velocities of fecal pellets
      along the colon. This raises the fundamental question: what mechanisms underlie
      hexamethonium-resistant peristalsis? We investigated whether blockade of the
      major receptors that underlie excitatory neuromuscular transmission is required
      for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements
      was used to make spatiotemporal maps and determine the velocity of peristalsis.
      Propagation of artificial fecal pellets in the guinea pig distal colon was
      studied in hexamethonium, atropine, omega-conotoxin (GVIA), ibodutant (MEN
      15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In
      contrast, omega-conotoxin abolished peristalsis in some preparations and reduced
      the velocity of propagation in all remaining specimens. Peristalsis could still
      occur in some animals in the presence of hexamethonium + atropine + ibodutant +
      omega-conotoxin. Peristalsis never occurred in the presence of TTX. The major
      finding of the current study is the unexpected observation that peristalsis can
      occur after blockade of the major excitatory neuroneuronal and neuromuscular
      transmitters. Also, the colon retained an intrinsic polarity in the presence of
      these antagonists and was only able to expel pellets in an aboral direction. The
      nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and
      facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory
      neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be
      identified. 

PMID- 24113767
TI  - Dietary fat sources differentially modulate intestinal barrier and hepatic
      inflammation in alcohol-induced liver injury in rats.
AB  - Endotoxemia is a causal factor in the development of alcoholic liver injury. The
      present study aimed at determining the interactions of ethanol with different fat
      sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or
      ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber
      DeCarli formula, with 30% total calories derived from corn oil (rich in
      polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in
      the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain
      saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium
      chain saturated fatty acids). Ethanol feeding increased hepatic lipid
      accumulation and inflammatory cell infiltration and perturbed hepatic and serum
      metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced
      liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and
      MCT also normalized ethanol-induced hepatic macrophage activation, cytokine
      expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin
      level, which was normalized by MCT but not CB. In accordance, ethanol-induced
      downregulations of intestinal occludin and zonula occludens-1 were normalized by
      MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level
      in association with upregulation of an endotoxin detoxifying enzyme,
      argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in
      impaired endotoxin clearance and upregulated cytokine expression. These data
      demonstrate that the protection of saturated fats against alcohol-induced liver
      injury occur via different actions at the gut-liver axis and are chain length
      dependent. 

PMID- 24113768
TI  - Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis
      development in a rodent model.
AB  - Gut microbiota alterations are associated with various disorders. In this study,
      gut microbiota changes were investigated in a methionine-choline-deficient (MCD)
      diet-induced nonalcoholic steatohepatitis (NASH) rodent model, and the effects of
      administering Lactobacillus casei strain Shirota (LcS) on the development of NASH
      were also investigated. Mice were divided into three groups, given the normal
      chow diet (NCD), MCD diet, or the MCD diet plus daily oral administration of LcS
      for 6 wk. Gut microbiota analyses for the three groups revealed that lactic acid
      bacteria such as Bifidobacterium and Lactobacillus in feces were markedly reduced
      by the MCD diet. Interestingly, oral administration of LcS to MCD diet-fed mice
      increased not only the L. casei subgroup but also other lactic acid bacteria.
      Subsequently, NASH development was evaluated based on hepatic histochemical
      findings, serum parameters, and various mRNA and/or protein expression levels.
      LcS intervention markedly suppressed MCD-diet-induced NASH development, with
      reduced serum lipopolysaccharide concentrations, suppression of inflammation and
      fibrosis in the liver, and reduced colon inflammation. Therefore, reduced
      populations of lactic acid bacteria in the colon may be involved in the
      pathogenesis of MCD diet-induced NASH, suggesting normalization of gut microbiota
      to be effective for treating NASH. 

PMID- 24113769
TI  - Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion
      within liver sinusoids during endotoxemia.
AB  - A key pathological feature of the systemic inflammatory response of
      sepsis/endotoxemia is the accumulation of neutrophils within the microvasculature
      of organs such as the liver, where they cause tissue damage and vascular
      dysfunction. There is emerging evidence that the vascular endothelium is critical
      to the orchestration of inflammatory responses to blood-borne microbes and
      microbial products in sepsis/endotoxemia. In this study, we aimed to understand
      the role of endothelium, and specifically endothelial TLR4 activation, in the
      regulation of neutrophil recruitment to the liver during endotoxemia. Intravital
      microscopy of bone marrow chimeric mice revealed that TLR4 expression by non-bone
      marrow-derived cells was required for neutrophil recruitment to the liver during
      endotoxemia. Furthermore, LPS-induced neutrophil adhesion in liver sinusoids was
      equivalent between wild-type mice and transgenic mice that express TLR4 only on
      endothelium (tlr4(-/-)Tie2(tlr4)), revealing that activation of endothelial TLR4
      alone was sufficient to initiate neutrophil adhesion. Neutrophil arrest within
      sinusoids of endotoxemic mice requires adhesive interactions between neutrophil
      CD44 and endothelial hyaluronan. Intravital immunofluorescence imaging
      demonstrated that stimulation of endothelial TLR4 alone was sufficient to induce
      the deposition of serum-derived hyaluronan-associated protein (SHAP) within
      sinusoids, which was required for CD44/hyaluronan-dependent neutrophil adhesion.
      In addition to endothelial TLR4 activation, Kupffer cells contribute to
      neutrophil recruitment via a distinct CD44/HA/SHAP-independent mechanism. This
      study sheds new light on the control of innate immune activation within the liver
      vasculature during endotoxemia, revealing a key role for endothelial cells as
      sentinels in the detection of intravascular infections and coordination of
      neutrophil recruitment to the liver. 

PMID- 24113771
TI  - Inspiratory muscle training improves antireflux barrier in GERD patients.
AB  - The crural diaphragm (CD) is an essential component of the esophagogastric
      junction (EGJ), and inspiratory exercises may modify its function. This study's
      goal is to verify if inspiratory muscle training (IMT) improves EGJ motility and
      gastroesophageal reflux (GER). Twelve GER disease [GERD; 7 males, 20-47 yr, 9
      esophagitis, and 3 nonerosive reflex disease (NERD)] and 7 healthy volunteers (3
      males, 20-41 yr) performed esophageal pH monitoring, manometry, and heart rate
      variability (HRV) studies. A 6-cm sleeve catheter measured average EGJ pressure
      during resting, peak inspiratory EGJ pressures during sinus arrhythmia maneuver
      (SAM) and inhalations under 17-, 35-, and 70-cmH2O loads (TH maneuvers), and
      along 1 h after a meal. GERD patients entered a 5-days-a-week IMT program. One
      author scored heartburn and regurgitation before and after IMT. IMT increased
      average EGJ pressure (19.7 +/- 2.4 vs. 29.5 +/- 2.1 mmHg; P < 0.001) and
      inspiratory EGJ pressure during SAM (89.6 +/- 7.6 vs. 125.6 +/- 13.3 mmHg; P =
      0.001) and during TH maneuvers. The EGJ-pressure gain across 35- and 70-cmH2O
      loads was lower for GERD volunteers. The number and cumulative duration of the
      transient lower esophageal sphincter relaxations decreased after IMT. Proximal
      progression of GER decreased after IMT but not the distal acid exposure. Low
      frequency power increased after IMT and the higher its increment the lower the
      increment of supine acid exposure. IMT decreased heartburn and regurgitation
      scores. In conclusion, IMT improved EGJ pressure, reduced GER proximal
      progression, and reduced GERD symptoms. Some GERD patients have a CD failure, and
      IMT may prove beneficial as a GERD add-on treatment. 

PMID- 24113770
TI  - Increased plasma corticosterone contributes to the development of alcoholic fatty
      liver in mice.
AB  - Ethanol ingestion increases endogenous glucocorticoid levels in both humans and
      rodents. The present study aimed to define a mechanistic link between the
      increased glucocorticoids and alcoholic fatty liver in mice. Plasma
      corticosterone levels were not affected in mice on a 2-wk ethanol diet regimen
      but significantly increased upon 4 wk of ethanol ingestion. Accordingly, hepatic
      triglyceride levels were not altered after 2 wk of ethanol ingestion but were
      elevated at 4 wk. Based on the observation that 2 wk of ethanol ingestion did not
      significantly increase endogenous corticosterone levels, we administered
      exogenous glucocorticoids along with the 2-wk ethanol treatment to determine
      whether the elevated glucocorticoid contributes to the development of alcoholic
      fatty liver. Mice were subjected to ethanol feeding for 2 wk with or without
      dexamethasone administration. Hepatic triglyceride contents were not affected by
      either ethanol or dexamethasone alone but were significantly increased by
      administration of both. Microarray and protein level analyses revealed two
      distinct changes in hepatic lipid metabolism in mice administered with both
      ethanol and dexamethasone: accelerated triglyceride synthesis by diacylglycerol O
      acyltransferase 2 and suppressed fatty acid beta-oxidation by long-chain acyl-CoA
      synthetase 1, carnitine palmitoyltransferase 1a, and acyl-CoA oxidase 1. A
      reduction of hepatic peroxisome proliferation activator receptor-alpha (PPAR
      alpha) was associated with coadministration of ethanol and dexamethasone. These
      findings suggest that increased glucocorticoid levels may contribute to the
      development of alcoholic fatty liver, at least partially, through hepatic PPAR
      alpha inactivation. 

PMID- 24113772
TI  - Differential expression of heat shock proteins in healthy and diseased human
      renal allografts.
AB  - BACKGROUND: Determining patterns of heat shock protein (Hsp) induction in normal
      kidneys and transplanted kidneys could provide insight into pathogenesis. The aim
      was to evaluate Hsp expression in normal kidneys, normal renal allografts and
      diseased renal allografts. MATERIAL AND METHODS: Immunohistochemical staining for
      Hsp27, 60, 70i and 72/73 was performed on 11 morphologically normal human kidney
      nephrectomy specimens and needle biopsies of 32 human renal allografts. RESULTS:
      Within the normal kidney, Hsp27 was detected in the endothelium, distal tubules
      and collecting ducts. Hsp60 was present within the distal convoluted tubules and
      ascending thick limb. Inducible Hsp70 (Hsp70i) was identified in the collecting
      ducts and ascending thick limb. Constitutively-expressed Hsp72/73 stained within
      podocytes and parietal epithelium. In renal allografts the low grade constitutive
      expression of Hsp in normal allografts became changed in disease. In acute
      cellular rejection and cyclophilin toxicity, distal tubules showed increased
      cytoplasmic immunopositivity for Hsp27, 60 and 70i. In chronic allograft
      nephropathy there was also induction of Hsp27, 60 and 70i in the distal tubules
      but this was less pronounced. Constitutively-expressed Hsp72/73 wasn't
      significantly induced in any diseased grafts. CONCLUSIONS: Multiple Hsps are
      induced in diseased renal allografts, particularly within the distal nephron and
      the induction profile differs between diseases.

PMID- 24113774
TI  - Electrochemical detection of commercial silver nanoparticles: identification,
      sizing and detection in environmental media.
AB  - The electrochemistry of silver nanoparticles contained in a consumer product has
      been studied. The redox properties of silver particles in a commercially
      available disinfectant cleaning spray were investigated via cyclic voltammetry
      before particle-impact voltammetry was used to detect single particles in both a
      typical aqueous electrolyte and authentic seawater media. We show that particle
      impact voltammetry is a promising method for the detection of nanoparticles that
      have leached into the environment from consumer products, which is an important
      development for the determination of risks associated with the incorporation of
      nanotechnology into everyday products. 

PMID- 24113773
TI  - Inferring tumour purity and stromal and immune cell admixture from expression
      data.
AB  - Infiltrating stromal and immune cells form the major fraction of normal cells in
      tumour tissue and not only perturb the tumour signal in molecular studies but
      also have an important role in cancer biology. Here we describe 'Estimation of
      STromal and Immune cells in MAlignant Tumours using Expression data' (ESTIMATE)-
      a method that uses gene expression signatures to infer the fraction of stromal
      and immune cells in tumour samples. ESTIMATE scores correlate with DNA copy
      number-based tumour purity across samples from 11 different tumour types,
      profiled on Agilent, Affymetrix platforms or based on RNA sequencing and
      available through The Cancer Genome Atlas. The prediction accuracy is further
      corroborated using 3,809 transcriptional profiles available elsewhere in the
      public domain. The ESTIMATE method allows consideration of tumour-associated
      normal cells in genomic and transcriptomic studies. An R-library is available on
      https://sourceforge.net/projects/estimateproject/.

PMID- 24113776
TI  - Highly cited publications in pediatric neurosurgery: part 2.
AB  - PURPOSE: Citation counting can be used to evaluate the impact an article has made
      on its discipline. This study characterizes the most cited articles related to
      clinical pediatric neurosurgery as of July 2013. METHODS: A list of search terms
      was computed using Thomson Reuters Web of Science(r) (WOS) to capture the 100
      most cited articles in the overall literature and the top 50 articles from 2002
      to 2012 related to clinical pediatric neurosurgery from non-dedicated pediatric
      neurosurgical journals. The following information was recorded for each article:
      number of authors, country of origin, citation count adjusted for number of years
      in print, topic, and level of evidence. RESULTS: The 100 most cited articles
      appeared in 44 journals. Publication dates ranged from 1986 to 2008; two were
      class 1 evidence, nine class 2, 26 class 3, and 52 class 4. Citations ranged from
      90 to 321 (mean = 131); average time-adjusted citation count was 10. The 50 most
      cited articles from 2002 to 2012 appeared in 31 journals; four were class 2
      evidence, 15 class 3, and 21 class 4. Citations ranged from 68 to 245 (mean =
      103); average time-adjusted citation count was 13. CONCLUSION: Overall, papers
      from non-pediatric neurosurgical journals had higher citation counts and improved
      level of evidence grades compared to articles from pediatric neurosurgical
      periodicals. An original paper related to clinical pediatric neurosurgery in a
      non-pediatric neurosurgical journal having a total citation count of 100-150 or
      more and an average citation count of 10-15 per year or more can be considered a
      high-impact publication.

PMID- 24113779
TI  - Sensitive and selective detection of cesium via fluorescence quenching.
AB  - Herein we report a robust and easy method for detecting cesium metal ion (Cs(+))
      in partially aqueous solutions using the fluorescence quenching of 2,4-bis[4-(N,N
      dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both
      highly sensitive (low limits of detection) and selective (limited response to
      other metals) for cesium ion detection. The detection is likely based on the
      metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor
      acceptor-donor architecture and leads to efficient quenching. 

PMID- 24113780
TI  - Arterial aneurysms: autosomal dominant polycystic kidney disease, Marfan syndrome
      or both?

PMID- 24113777
TI  - Tissue distribution and thyroid hormone effects on mRNA abundance for membrane
      transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in
      a teleost fish.
AB  - Many of the actions of thyroid hormones (THs) occur via TH binding to
      intracellular receptors. Although it was long thought that THs diffused passively
      across plasma membranes, it is now recognized that cellular entry is mediated by
      a variety of membrane transporter proteins. In this study, we identified cDNAs
      encoding the TH transporters monocarboxylate transferases 8 (mct8) and 10 (mct10)
      as well as eight distinct organic anion-transporting polypeptide (oatp) proteins
      from fathead minnow (Pimephales promelas). Analysis of the tissue distribution of
      transporter mRNAs revealed that mct8 and mct10 transcripts were both abundant in
      liver, but also present at lower levels in brain, gonad and other tissues.
      Transcripts encoding oatp1c1 were highly abundant in brain, liver and gonad, and
      exhibited significant sex differences in the liver and gonad. Treatment of adult
      male minnows with 3,5,3'-triiodothyronine (T3) or the goitrogen methimazole
      altered gene transcript abundance for several transporters. Fish given exogenous
      T3 had reduced mct8 and oapt1c1 mRNA levels in the liver compared to methimazole
      treated fish. In the brain, transcripts for mct8, mct10, oatp2b1, and oatp3a1
      were each reduced in abundance in fish with elevated T3. As a whole, these
      results provide evidence that TH status influences the transcriptional dynamics
      of mct8, mct10 and several Oatp genes including oatp1c1 in teleost fish. 

PMID- 24113781
TI  - Tolvaptan increases urine and ultrafiltration volume for patients with oliguria
      undergoing peritoneal dialysis.
AB  - BACKGROUND: Hypoalbuminemia caused by peritoneal dialysate protein loss,
      frequently occurs in patients on peritoneal dialysis (PD) and is associated with
      an increased risk of death. We investigate whether PD dialysis exchange volume
      (PD volume) could be reduced with tolvaptan (TVP) through increased urine volume
      (UV). METHODS: The study included 11 stable patients with oliguria undergoing PD.
      The following parameters were examined-diuretic response and the effect of TVP on
      peritoneal ultrafiltration (UF), body weight, serum albumin, sodium, arm muscle
      area (AMA), PD volume, dialysis efficiency calculator (K t/V), and urine and
      serum osmolarity (OSM). RESULTS: The average UV increased from 428 +/- 178 to 906
      +/- 285 mL (p = 0.018 by paired t test). Average weekly PD volume decreased from
      28,836 +/- 5,699 to 23,872 +/- 3,569 mL (p = 0.04 by paired t test). Average UF
      increased from 283 +/- 147 to 575 +/- 135 mL (p = 0.019 by paired t test). On the
      other hand, there was no significant difference in the average dialysate K t/V
      before and after TVP treatment. Serum sodium, AMA, and serum albumin levels were
      not statistically different before and after TVP treatment. The urine and serum
      OSM ratio of effective cases before TVP treatment was higher than that of
      ineffective cases (p = 0.024 by unpaired t test). CONCLUSION: Our results
      indicate that TVP is useful for patients on continuous ambulatory PD who have
      oliguria and high urine osmolarity. Furthermore, we can reduce PD volume to
      maintain their nutritional status.

PMID- 24113782
TI  - Association between warfarin use and incidence of ischemic stroke in Japanese
      hemodialysis patients with chronic sustained atrial fibrillation: a prospective
      cohort study.
AB  - BACKGROUND: Although generally recommended for atrial fibrillation (AF) in the
      general population, the efficacy and safety of warfarin in hemodialysis patients
      remains controversial. Warfarin use in hemodialysis patients may confer an
      additional risk of bleeding that is not appreciated in patients without renal
      failure because hemodialysis patients have platelet defects and receive
      anticoagulation agents during dialysis. The incidence of major bleeding was
      reported to be higher in Japanese AF patients on warfarin therapy compared to
      patients in other countries, suggesting that racial differences may influence
      bleeding tendency. Thus, examining risks and benefits of warfarin therapy in
      Japanese hemodialysis patients with AF is important. METHODS: In order to
      determine associations between warfarin use and new ischemic stroke events, major
      bleeding, and all-cause mortality, a prospective cohort study of 60 Japanese
      hemodialysis patients with chronic sustained AF was conducted using Cox
      proportional modeling and propensity score matching. RESULTS: The mean patient
      age was 68.1 years. During 110 person-years of follow-up, 13 ischemic strokes
      occurred. After adjusting for CHADS2 score, warfarin use was not associated with
      a significant reduction in ischemic stroke events [hazard ratio (HR) 3.36; 95 %
      confidence interval (CI) 0.94-11.23]. Similar results were obtained after
      propensity score matching (HR 3.36; 95 % CI 0.67-16.66). Warfarin use was not
      associated with significant increases in major bleeding or all-cause mortality.
      CONCLUSIONS: These results suggest that warfarin may not prevent ischemic stroke
      in Japanese hemodialysis patients with chronic sustained AF. Adequately powered
      studies are needed to determine the risks and benefits of anticoagulation therapy
      in these patients.

PMID- 24113783
TI  - Initial exploration of oral pazopanib in healthy participants and patients with
      age-related macular degeneration.
AB  - IMPORTANCE: Neovascular age-related macular degeneration (AMD) is managed with
      intravitreal anti-vascular endothelial growth factor therapy; however, the burden
      of care is high and alternate approaches could be beneficial. OBJECTIVE To
      identify an acceptable dose of oral pazopanib for investigation in AMD. DESIGN,
      SETTING, AND PARTICIPANTS: Fourteen-day, placebo-controlled, dose-rising study in
      72 healthy participants and 28-day phase 2a open-label study in 15 patients with
      subfoveal choroidal neovascularization secondary to AMD at a clinical unit for
      healthy participants and outpatient for patients with AMD. INTERVENTION: Oral
      pazopanib tablets, 5 to 30 mg daily (healthy participants) and 15 mg daily
      (patients with AMD). MAIN OUTCOMES AND MEASURES: Safety, pharmacokinetics, best
      corrected visual acuity, central retinal lesion thickness, and central retinal
      thickness at day 29. RESULTS: Oral pazopanib up to 30 mg daily in healthy
      participants and 15 mg daily in patients with AMD was well tolerated. Six of 15
      patients received rescue therapy before day 29; all had the CFH Y402H CC "high
      risk" genotype for AMD. Nine patients completed the study without rescue with
      improvements from baseline in best-corrected visual acuity (8 Early Treatment
      Diabetic Retinopathy Study letters), central retinal lesion thickness (-50.94
      um), and central retinal thickness (-50.28 um). There was a trend for association
      between the CFH Y402H T allele ("low risk" for AMD, n = 6) and improvement.
      CONCLUSIONS AND RELEVANCE: Oral pazopanib (15 mg daily) was well tolerated and
      resulted in improvements in mean best-corrected visual acuity, central retinal
      lesion thickness, and central retinal thickness at day 29 in a per-protocol,
      nonrescued AMD population (n = 9). It is postulated that CFH Y402H genotype may
      help predict which patients respond to pazopanib. The size and length limitations
      of this study warrant further investigation to determine if oral pazopanib may be
      an appropriate treatment for a subset of neovascular patients with AMD or as an
      adjunct to standard of care. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01051700 and NCT01154062.

PMID- 24113784
TI  - Subcellular calcium measurements in mammalian cells using jellyfish photoprotein
      aequorin-based probes.
AB  - The jellyfish Aequorea victoria produces a 22-kDa protein named aequorin that has
      had an important role in the study of calcium (Ca(2+)) signaling. Aequorin reacts
      with Ca(2+) via oxidation of the prosthetic group, coelenterazine, which results
      in emission of light. This signal can be detected by using a special luminescence
      reader (called aequorinometer) or luminescence plate readers. Here we describe
      the main characteristics of aequorin as a Ca(2+) probe and how to measure Ca(2+)
      in different intracellular compartments of animal cells (cytosol, different
      mitochondrial districts, nucleus, endoplasmic reticulum (ER), Golgi apparatus,
      peroxisomes and subplasma-membrane cytosol), ranging from single-well analyses to
      high-throughput screening by transfecting animal cells using DNA vectors carrying
      recombinant aequorin chimeras. The use of aequorin mutants and modified versions
      of coelenterazione increases the range of calcium concentrations that can be
      recorded. Cell culture and transfection takes ~3 d. An experiment including
      signal calibration and the subsequent analyses will take ~1 d. 

PMID- 24113785
TI  - High-throughput analysis of meiotic crossover frequency and interference via flow
      cytometry of fluorescent pollen in Arabidopsis thaliana.
AB  - During meiosis, reciprocal exchange between homologous chromosomes occurs as a
      result of crossovers (COs). CO frequency varies within genomes and is subject to
      genetic, epigenetic and environmental control. As robust measurement of COs is
      limited by their low numbers, typically 1-2 per chromosome, we adapted flow
      cytometry for use with Arabidopsis transgenic fluorescent protein-tagged lines
      (FTLs) that express eCFP, dsRed or eYFP fluorescent proteins in pollen.
      Segregation of genetically linked transgenes encoding fluorescent proteins of
      distinct colors can be used to detect COs. The fluorescence of up to 80,000
      pollen grains per individual plant can be measured in 10-15 min using this
      protocol. A key element of CO control is interference, which inhibits closely
      spaced COs. We describe a three-color assay for the measurement of CO frequency
      in adjacent intervals and calculation of CO interference. We show that this
      protocol can be used to detect changes in CO frequency and interference in the
      fancm zip4 double mutant. By enabling high-throughput measurement of CO frequency
      and interference, these methods will facilitate genetic dissection of meiotic
      recombination control. 

PMID- 24113786
TI  - Microfabrication of human organs-on-chips.
AB  - 'Organs-on-chips' are microengineered biomimetic systems containing microfluidic
      channels lined by living human cells, which replicate key functional units of
      living organs to reconstitute integrated human organ-level pathophysiology in
      vitro. These microdevices can be used to test efficacy and toxicity of drugs and
      chemicals, and to create in vitro models of human disease. Thus, they potentially
      represent low-cost alternatives to conventional animal models for pharmaceutical,
      chemical and environmental applications. Here we describe a protocol for the
      fabrication, microengineering and operation of these microfluidic organ-on-chip
      systems. First, microengineering is used to fabricate a multilayered microfluidic
      device that contains two parallel elastomeric microchannels separated by a thin
      porous flexible membrane, along with two full-height, hollow vacuum chambers on
      either side; this requires ~3.5 d to complete. To create a 'breathing' lung-on-a
      chip that mimics the mechanically active alveolar-capillary interface of the
      living human lung, human alveolar epithelial cells and microvascular endothelial
      cells are cultured in the microdevice with physiological flow and cyclic suction
      applied to the side chambers to reproduce rhythmic breathing movements. We
      describe how this protocol can be easily adapted to develop other human organ
      chips, such as a gut-on-a-chip lined by human intestinal epithelial cells that
      experiences peristalsis-like motions and trickling fluid flow. Also, we discuss
      experimental techniques that can be used to analyze the cells in these organ-on
      chip devices. 

PMID- 24113788
TI  - Ubiquitin: molecular modeling and simulations.
AB  - The synthesis and destruction of proteins are imperative for maintaining their
      cellular homeostasis. In the 1970s, Aaron Ciechanover, Avram Hershko, and Irwin
      Rose discovered that certain proteins are tagged by ubiquitin before degradation,
      a discovery that awarded them the 2004 Nobel Prize in Chemistry. Compelling data
      gathered during the last several decades show that ubiquitin plays a vital role
      not only in protein degradation but also in many cellular functions including DNA
      repair processes, cell cycle regulation, cell growth, immune system
      functionality, hormone-mediated signaling in plants, vesicular trafficking
      pathways, regulation of histone modification and viral budding. Due to the
      involvement of ubiquitin in such a large number of diverse cellular processes,
      flaws and impairments in the ubiquitin system were found to be linked to cancer,
      neurodegenerative diseases, genetic disorders, and immunological disorders.
      Hence, deciphering the dynamics and complexity of the ubiquitin system is of
      significant importance. In addition to experimental techniques, computational
      methodologies have been gaining increasing influence in protein research and are
      used to uncover the structure, stability, folding, mechanism of action and
      interactions of proteins. Notably, molecular modeling and molecular dynamics
      simulations have become powerful tools that bridge the gap between structure and
      function while providing dynamic insights and illustrating essential mechanistic
      characteristics. In this study, we present an overview of molecular modeling and
      simulations of ubiquitin and the ubiquitin system, evaluate the status of the
      field, and offer our perspective on future progress in this area of research. 

PMID- 24113787
TI  - Optimized RNA ISH, RNA FISH and protein-RNA double labeling (IF/FISH) in
      Drosophila ovaries.
AB  - In situ hybridization (ISH) is a powerful technique for detecting nucleic acids
      in cells and tissues. Here we describe three ISH procedures that are optimized
      for Drosophila ovaries: whole-mount, digoxigenin-labeled RNA ISH; RNA fluorescent
      ISH (FISH); and protein immunofluorescence (IF)-RNA FISH double labeling
      (IF/FISH). Each procedure balances conflicting requirements for permeabilization,
      fixation and preservation of antigenicity to detect RNA and protein expression
      with high resolution and sensitivity. The ISH protocol uses alkaline phosphatase
      conjugated digoxigenin antibodies followed by a color reaction, whereas FISH
      detection involves tyramide signal amplification (TSA). To simultaneously
      preserve antigens for protein detection and enable RNA probe penetration for
      IF/FISH, we perform IF before FISH and use xylenes and detergents to permeabilize
      the tissue rather than proteinase K, which can damage the antigens. ISH and FISH
      take 3 d to perform, whereas IF/FISH takes 5 d. Probe generation takes 1 or 2 d
      to perform. 

PMID- 24113789
TI  - Dynamics of adhesion molecule domains on neutrophil membranes: surfing the
      dynamic cell topography.
AB  - Lateral organization and mobility of adhesion molecules play a significant role
      in determining the avidity with which cells can bind to target cells or surfaces.
      Recently, we have shown that the lateral mobility of the principal adhesion
      molecules on neutrophils is lower for rolling associated adhesion molecules
      (RAAMs: L-selectin and PSGL-1) than for beta2 integrins (LFA-1 and Mac-1). Here
      we report that all four adhesion molecules exhibit distinct punctate
      distributions that are mobile on the cell surface. Using uniform illumination
      image correlation microscopy, we measure the lateral mobility of these
      topologically distinct domains. For all four molecules, we find that diffusion
      coefficients calculated from domain mobility agree with measurements we made
      previously using fluorescence recovery after photobleaching. This agreement
      indicates that the transport of receptors on the surface of the resting
      neutrophil is dominated by the lateral movement of domains rather than individual
      molecules. The diffusion of pre-assembled integrin domains to zones of
      neutrophil/endothelial contact may provide a mechanism to facilitate high avidity
      adhesion during the earliest stages of firm arrest. 

PMID- 24113790
TI  - Taming the ABO barrier in transplantation.

PMID- 24113791
TI  - Genotype of proband and thrombophilia screening.

PMID- 24113792
TI  - Two targets for the price of one.

PMID- 24113793
TI  - Therapy of pediatric ALL: from Bowie to Obama.

PMID- 24113794
TI  - Another piece of the AML puzzle.

PMID- 24113795
TI  - Sitosterolemia: platelets on high-sterol diet.

PMID- 24113796
TI  - HO-1 and CO: fighters vs sickle cell disease?

PMID- 24113797
TI  - Body size in early life and breast cancer risk in African American and European
      American women.
AB  - PURPOSE: There is growing evidence that body size in early life influences
      lifetime breast cancer risk, but little is known for African American (AA) women.
      METHODS: We evaluated body size during childhood and young adulthood and breast
      cancer risk among 1,751 cases [979 AA and 772 European American (EA)] and 1,673
      controls (958 AA and 715 EA) in the Women's Circle of Health Study. Odds ratio
      (OR) and 95 % confidence intervals (CI) were computed using logistic regression
      models while adjusting for potential covariates. RESULTS: Among AA women, being
      shorter at 7-8 years compared to peers was associated with increased
      postmenopausal breast cancer risk (OR 1.68, 95 % CI 1.02-2.74), and being heavier
      at menarche with decreased postmenopausal breast cancer risk, although of
      borderline significance (OR 0.45, 95 % CI 0.20-1.02). For EA women, being shorter
      from childhood through adolescence, particularly at menarche, was associated with
      reduced premenopausal breast cancer risk (OR 0.55, 95 % CI 0.31-0.98). After
      excluding hormone replacement therapy users, an inverse association with
      postmenopausal breast cancer was found among EA women reporting to be heavier
      than their peers at menarche (OR 0.18, 95 % CI 0.04-0.79). The inverse
      relationship between BMI at age 20 and breast cancer risk was stronger and only
      statistically significant in EA women. No clear association with weight gain
      since age 20 was found. CONCLUSIONS: Findings suggest that the impact of
      childhood height on breast cancer risk may differ for EA and AA women and confirm
      the inverse association previously reported in EA populations with adolescent
      body fatness, in AA women.

PMID- 24113799
TI  - Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60
      publications with 111 individual studies.
AB  - Several potentially functional variants of Nijmegen breakage syndrome 1 (NBS1)
      have been implicated in cancer risk, but individually studies showed inconclusive
      results. In this study, a meta-analysis based on 60 publications with a total of
      39 731 cancer cases and 64 957 controls was performed. The multivariate method
      and the model-free method were adopted to determine the best genetic model. It
      was found that rs2735383 variant genotypes were associated with significantly
      increased overall risk of cancer under the recessive genetic model [odds ratio
      (OR) =1.12, 95% confidence interval (CI): 1.02-1.22, P = 0.013]. Similar results
      were found for rs1063054 under the dominant model effect (OR = 1.12, 95% CI: 1.01
      1.23, P = 0.024). The I171V mutation, 657del5 mutation and R215W mutation also
      contribute to the development of cancer (for I171V, OR = 3.93, 95% CI: 1.68-9.20,
      P = 0.002; for 657del5, OR = 2.79, 95% CI: 2.17-3.68, P < 0.001; for R215W, OR =
      1.77, 95% CI: 1.07-2.91, P = 0.025). From stratification analyses, an effect
      modification of cancer risks was found in the subgroups of tumour site and
      ethnicity for rs2735383, whereas the I171V, 657del5 and R215W showed a
      deleterious effect of cancer susceptibility in the subgroups of tumour site.
      However, rs1805794, D95N and P266L did not appear to have an effect on cancer
      risk. These results suggest that rs2735383, rs1063054, I171V, 657del5 and R215W
      are low-penetrance risk factors for cancer development. 

PMID- 24113798
TI  - Safety of purified chick embryo cell rabies vaccine (Vaxirab N) after pre
      exposure prophylaxis against rabies in children: is only adverse event profile
      enough?

PMID- 24113801
TI  - Six-year trend analysis of nosocomial candidemia and risk factors in two
      intensive care hospitals in Mato Grosso, midwest region of Brazil.
AB  - We conducted this cross-sectional retrospective study using clinical and
      laboratory data from two tertiary hospitals in Cuiaba, Mato Grosso, Brazil, in
      order to explore the risk factors and estimate mortality, prevalence and
      lethality of candidemia between 2006 and 2011. A total of 130 episodes of
      candidemia were identified. The prevalence of candidemia was 1.8 per 1,000
      admissions, the mortality rate was 0.9 per 1,000 admissions, and the lethality
      was 49.2 %. The main agent in this population was Candida parapsilosis (n = 50),
      followed by C. albicans (n = 45). Comparison between the numbers of episodes in
      the two triennia revealed that the non-albicans group grew by 48.2 %. The
      distribution of yeast species of Candida per hospital unit revealed that C.
      albicans was more prevalent than C. parapsilosis in the adult ICU and C.
      parapsilosis was more prevalent than C. albicans in the neonatal ICU. Patients
      remained hospitalized for an average of 53.5 days. Central venous catheters,
      parenteral nutrition and age were the variables that proved to be independent in
      the multivariate analysis and that maintained a statistically significant
      association with the incidence of death in patients with candidemia. The annual
      prevalence of candidemia showed a significant increase in the second triennium
      (2009-2011) compared with the first (2006-2008) probably due to increased
      exposure to risk factors: central venous catheter, H2 blockers, nutrition
      parenteral corticosteroids and mean hospital duration. 

PMID- 24113802
TI  - Database queries for hospitalizations for acute congestive heart failure:
      flexible methods and validation based on set theory.
AB  - BACKGROUND AND OBJECTIVE: Electronic health records databases are increasingly
      used for identifying cohort populations, covariates, or outcomes, but discerning
      such clinical 'phenotypes' accurately is an ongoing challenge. We developed a
      flexible method using overlapping (Venn diagram) queries. Here we describe this
      approach to find patients hospitalized with acute congestive heart failure (CHF),
      a sampling strategy for one-by-one 'gold standard' chart review, and calculation
      of positive predictive value (PPV) and sensitivities, with SEs, across different
      definitions. MATERIALS AND METHODS: We used retrospective queries of
      hospitalizations (2002-2011) in the Indiana Network for Patient Care with any CHF
      ICD-9 diagnoses, a primary diagnosis, an echocardiogram performed, a B
      natriuretic peptide (BNP) drawn, or BNP >500 pg/mL. We used a hybrid between
      proportional sampling by Venn zone and over-sampling non-overlapping zones. The
      acute CHF (presence/absence) outcome was based on expert chart review using a
      priori criteria. RESULTS: Among 79,091 hospitalizations, we reviewed 908. A query
      for any ICD-9 code for CHF had PPV 42.8% (SE 1.5%) for acute CHF and sensitivity
      94.3% (1.3%). Primary diagnosis of 428 and BNP >500 pg/mL had PPV 90.4% (SE 2.4%)
      and sensitivity 28.8% (1.1%). PPV was <10% when there was no echocardiogram, no
      BNP, and no primary diagnosis. 'False positive' hospitalizations were for other
      heart disease, lung disease, or other reasons. CONCLUSIONS: This novel method
      successfully allowed flexible application and validation of queries for patients
      hospitalized with acute CHF.

PMID- 24113803
TI  - Renalase mRNA levels in the brain, heart, and kidneys of spontaneously
      hypertensive rats with moderate and high hypertension.
AB  - BACKGROUND: Renalase is a recently discovered secretory protein involved in
      regulation of arterial blood pressure in humans and animals. Results of animal
      experiments from independent laboratories indicate that administration of human
      recombinant renalase decreases blood pressure and some genetically predisposed
      hypertensive rats have lowered renalase levels. MATERIAL AND METHODS: The levels
      of renalase mRNA expression in brain hemispheres, heart, and kidneys of
      spontaneously hypertensive rats (SHR) with moderate (140-180 mm Hg) or high (>180
      mm Hg) hypertension and of control Wistar-Kyoto (WKY) rats were analyzed using
      real-time PCR. RESULTS: Spontaneously hypertensive rats with high hypertension
      (>180 mm Hg) had a lower renalase mRNA level in brain hemispheres, and higher
      heart and kidney renalase mRNA levels compared with control WKY rats. In SHR with
      a moderate increase in arterial blood pressure (140-180 mm Hg), the tissue
      renalase mRNA changed in the same direction but did not reach the level of
      statistical significance as compared with control rats. CONCLUSIONS: The results
      indicate that the development of hypertension in SHR is accompanied by altered
      expression of the renalase gene in the examined organs as compared with control
      WKY rats. The brain and peripheral tissues renalase mRNA levels demonstrate
      opposite trends, which are obviously crucial for impaired regulation of blood
      pressure in SHR.

PMID- 24113804
TI  - A pain in the...ventricle.

PMID- 24113805
TI  - Physicians' roles in creating health literate organizations: a call to action.

PMID- 24113807
TI  - Non-pharmacologic interventions to improve the sleep of hospitalized patients: a
      systematic review.
AB  - OBJECTIVES: Despite the known adverse effects of sleep deprivation on recovery
      from illness, studies have shown that sleep deprivation remains an incompletely
      addressed problem among acutely ill inpatients. Behavioral interventions are
      recommended as first-line therapy prior to using pharmacologic therapy due to the
      side effects of sedative hypnotics. The objective of this systematic review was
      to identify non-pharmacologic interventions that have been used to improve sleep
      quality and quantity of non-intensive care unit (ICU) inpatients. DATA SOURCES:
      PubMed, Embase, Web of Science, CINAHL, and Cochrane Library through January
      2013; manual searches of reference lists. STUDY ELIGIBILITY CRITERIA,
      PARTICIPANTS, INTERVENTIONS: Any study in which a non-pharmacologic intervention
      was conducted in a general inpatient setting, and nighttime sleep quantity or
      quality was assessed. STUDY APPRAISAL AND SYNTHESIS METHODS: Information on study
      design, populations, interventions, comparators, outcomes, time frame, and risk
      of bias were independently abstracted by two investigators. RESULTS: 13
      intervention studies with 1,154 participants were included. Four studies were
      randomized controlled trials. Seven studies had a low to medium risk of bias, and
      there was significant heterogeneity in the interventions. Relaxation techniques
      improved sleep quality 0-38%, interventions to improve sleep hygiene or reduce
      sleep interruptions improved sleep quantity 5%, and daytime bright light exposure
      improved sleep quantity 7-18%. LIMITATIONS: The heterogeneity in the types and
      dose of interventions, outcome measures, length of follow-up, differences in
      patient populations, and dearth of randomized trials may dilute effects seen or
      make it more difficult to draw conclusions. CONCLUSIONS AND IMPLICATIONS OF KEY
      FINDINGS: There is insufficient to low strength of evidence that any non
      pharmacologic intervention improves sleep quality or quantity of general
      inpatients. Further studies are needed in this area to guide clinicians.

PMID- 24113806
TI  - Awareness, treatment and control of hypertension among Filipino immigrants.
AB  - BACKGROUND: Filipino Americans have high rates of hypertension, yet little
      research has examined hypertension awareness, treatment, and control in this
      group. OBJECTIVE: In a community-based sample of hypertensive Filipino American
      immigrants, we identify 1) rates of hypertension awareness, treatment, and
      control; and 2) factors associated with awareness, treatment, and control.
      DESIGN: Cross-sectional analysis of survey data from health screenings collected
      from 2006 to 2010. PARTICIPANTS: A total of 566 hypertensive Filipino immigrants
      in New York City, New York and Jersey City, New Jersey. MAIN MEASURES:
      Hypertension awareness, treatment, and control. Participants were included in
      analysis if they were hypertensive, based on: a past physician diagnosis,
      antihypertensive medication use, and/or high blood pressure (BP) screening
      measurements. Demographic variables included sex, age, time in the United States,
      location of residence, and English spoken language fluency. Health-related
      variables included self-reported health, insurance status, diabetes diagnosis,
      high cholesterol diagnosis, clinical measures (body mass index [BMI], glucose,
      and cholesterol), exercise frequency, smoking status, cardiac event history,
      family history of cardiac event, and family history of hypertension. RESULTS:
      Among the hypertensive individuals, awareness, treatment, and control rates were
      suboptimal; 72.1 % were aware of their status, 56.5 % were on medication, and
      only 21.7 % had controlled BP. Factors related to awareness included older age,
      worse self-reported health, family history of hypertension, and a diagnosis of
      high cholesterol or diabetes; factors related to treatment included older age,
      longer time lived in the United States, and being a non-smoker; having health
      insurance was found to be the main predictor of hypertension control. Many
      individuals had other cardiovascular disease (CVD) risk factors; 60.4 % had a BMI
      >=25, 12.0 % had at-risk glucose measurements and 12.8 % had cholesterol >= 240.
      CONCLUSIONS: Hypertensive Filipinos exhibit poor hypertension management,
      warranting increased efforts to improve awareness, treatment and control.
      Culturally tailored public health strategies must be prioritized to reduce CVD
      risk factors among at-risk minority populations.

PMID- 24113808
TI  - Directive counsel and morally controversial medical decision-making: findings
      from two national surveys of primary care physicians.
AB  - BACKGROUND: Because of the potential to unduly influence patients' decisions,
      some ethicists counsel physicians to be nondirective when negotiating morally
      controversial medical decisions. OBJECTIVE: To determine whether primary care
      providers (PCPs) are less likely to endorse directive counsel for morally
      controversial medical decisions than for typical ones and to identify predictors
      of endorsing directive counsel in such situations. DESIGN AND PARTICIPANTS:
      Surveys were mailed to two separate national samples of practicing primary care
      physicians. Survey 1 was conducted from 2009 to 2010 on 1,504 PCPs; Survey 2 was
      conducted from 2010 to 2011 on 1,058 PCPs. MAIN MEASURES: Survey 1: After
      randomization, half of the PCPs were asked if physicians should encourage
      patients to make the decision that the physician believes is best (directive
      counsel) with respect to "typical" medical decisions and half were asked the same
      question with respect to "morally controversial" medical decisions. Survey 2:
      After reading a vignette in which a patient asked for palliative sedation to
      unconsciousness, PCPs were asked whether it would be appropriate for the
      patient's physician to encourage the patient to make the decision the physician
      believes is best. KEY RESULTS: Of 1,427 eligible physicians, 896 responded to
      Survey 1 (63 %). Physicians asked about morally controversial decisions were half
      as likely (35 % vs. 65 % for typical decisions, p < 0.001) to endorse directive
      counsel. Of 986 eligible physicians, 600 responded to Survey 2 (61 %). Two in
      five physicians (41 %) endorsed directive counsel after reading a vignette
      describing a patient requesting palliative sedation to unconsciousness; these
      physicians tended to be male and more religious. CONCLUSIONS: PCPs are less
      likely to endorse directive counsel when negotiating morally controversial
      medical decisions. Male physicians and those who are more religious are more
      likely to endorse directive counsel in these situations.

PMID- 24113809
TI  - The role of dendritic spine morphology in the compartmentalization and delivery
      of surface receptors.
AB  - Since AMPA receptors are major molecular players in both short- and long-term
      plasticity, it is important to identify the time-scales of and factors affecting
      the lateral diffusion of AMPARs on the dendrite surface. Using a mathematical
      model, we study how the dendritic spine morphology affects two processes: (1)
      compartmentalization of the surface receptors in a single spine to retain local
      chemistry and (2) the delivery of receptors to the post-synaptic density (PSD) of
      spines via lateral diffusion following insertion onto the dendrite shaft.
      Computing the mean first passage time (MFPT) of surface receptors on a sample of
      real spine morphologies revealed that a constricted neck and bulbous head serve
      to compartmentalize receptors, consistent with previous works. The residence time
      of a Brownian diffusing receptor on the membrane of a single spine was computed
      to be ~ 5 s. We found that the location of the PSD corresponds to the location at
      which the maximum MFPT occurs, the position that maximizes the residence time of
      a diffusing receptor. Meanwhile, the same geometric features of the spine that
      compartmentalize receptors inhibit the recruitment of AMPARs via lateral
      diffusion from dendrite insertion sites. Spines with narrow necks will trap a
      smaller fraction of diffusing receptors in the their PSD when considering
      competition for receptors between the spines, suggesting that ideal geometrical
      features involve a tradeoff depending on the intent of compartmentalizing the
      current receptor pool or recruiting new AMPARs in the PSD. The ultimate
      distribution of receptors among the spine PSDs by lateral diffusion from the
      dendrite shaft is an interplay between the insertion location and the shape and
      locations of both the spines and their PSDs. The time-scale for delivery of
      receptors to the PSD of spines via lateral diffusion was computed to be ~ 60 s. 

PMID- 24113810
TI  - Towards a quantitative understanding of palladium metal scavenger performance: an
      electronic structure calculation approach.
AB  - Dispersion corrected density functional theory (DFT-D) has been applied to
      understand the performance of several palladium metal scavengers. Nine different
      sulfur-based ligands and three different palladium metal sets have been
      investigated in detail. Based on a thorough analysis of the thermodynamic binding
      parameters DeltaH, DeltaG and DeltaS, we have identified the best binding modes
      for all scavenger ligands. Bis-monodentate coordination is favoured over
      chelation in DeltaH and DeltaG values for most of the scavenger ligands. Special
      attention has been paid to the ligand strain energies, which account for the
      structural changes of the ligands upon complexation indicating that small (5
      membered) chelates are considerably less favourable than expected. Some ligands
      can use their longest chain (>7-atoms) to yield trans chelates, which ligands
      with shorter chains (<=6-atoms) are unable to form. A secondary amino nitrogen
      (RR'NH) is found to be the best donor with highest binding enthalpy for Pd(ii)
      metal systems. In terms of the strength of the initial binding interactions, -SMe
      > -SH; capping thiols (-SH) as thioethers (-SMe) is therefore suggested to be an
      effective strategy in scavenger design. These observations mark the beginning of
      a knowledge base of the full range of possible interactions, leading to the
      construction of a sulfur ligand database for the design of scavenger systems. 

PMID- 24113811
TI  - Detection of adenosine triphosphate through polymerization-induced aggregation of
      actin-conjugated gold/silver nanorods.
AB  - We have developed a simple and selective nanosensor for the optical detection of
      adenosine triphosphate (ATP) using globular actin-conjugated gold/silver nanorods
      (G-actin-Au/Ag NRs). By simply mixing G-actin and Au/Ag NRs (length ~56 nm and
      diameter ~12 nm), G-actin-Au/Ag NRs were prepared which were stable in
      physiological solutions (25 mM Tris-HCl, 150 mM NaCl, 5.0 mM KCl, 3.0 mM MgCl2
      and 1.0 mM CaCl2; pH 7.4). Introduction of ATP into the G-actin-Au/Ag NR
      solutions in the presence of excess G-actin induced the formation of filamentous
      actin-conjugated Au/Ag NR aggregates through ATP-induced polymerization of G
      actin. When compared to G-actin-modified spherical Au nanoparticles having a size
      of 13 nm or 56 nm, G-actin-Au/Ag NRs provided better sensitivity for ATP, mainly
      because the longitudinal surface plasmon absorbance of the Au/Ag NR has a more
      sensitive response to aggregation. This G-actin-Au/Ag NR probe provided high
      sensitivity (limit of detection 25 nM) for ATP with remarkable selectivity (>10
      fold) over other adenine nucleotides (adenosine, adenosine monophosphate and
      adenosine diphosphate) and nucleoside triphosphates (guanosine triphosphate,
      cytidine triphosphate and uridine triphosphate). It also allowed the
      determination of ATP concentrations in plasma samples without conducting tedious
      sample pretreatments; the only necessary step was simple dilution. Our
      experimental results are in good agreement with those obtained from a commercial
      luciferin-luciferase bioluminescence assay. Our simple, sensitive and selective
      approach appears to have a practical potential for the clinical diagnosis of
      diseases (e.g. cystic fibrosis) associated with changes in ATP concentrations.

PMID- 24113812
TI  - Characterization of a putative stereoselective oxidoreductase from Gluconobacter
      oxydans and its application in producing ethyl (R)-4-chloro-3-hydroxybutanoate
      ester.
AB  - A gene encoding an NADH-dependent short-chain dehydrogenase/reductase (gox2036)
      from Gluconobacter oxydans 621H was cloned and heterogeneously expressed in
      Escherichia coli. The protein (Gox2036) was purified to homogeneity and
      biochemically characterized. Gox2036 was a homotetramer with a subunit size of
      approximately 28 kDa. Gox2036 had a strict requirement for NAD+/NADH as the
      cofactor. Gox2036 displayed preference for oxidation of secondary alcohols and
      2,3-diols as well as for reduction of alpha-diketones, hydroxy ketones, alpha
      ketoesters, and beta-ketoesters. However, Gox2036 was poorly active on 1,2-diols
      and acetoin and showed no activity on primary alcohols, polyols, and aldehydes.
      The optimum pH values for the oxidation and reduction reactions were 9 and 6,
      respectively. Gox2036 was highly selective in the reduction of various beta
      ketones and beta-ketoesters. Among the substrates tested, ethyl 4-chloro
      acetoacetate was reduced to ethyl (R)-4-chloro-3-hydroxybutanoate ester with an
      excellent conversion yield of 96.9 % and optical purity of >99 % e.e. using an
      efficient in situ NADH-recycling system involving glucose and a glucose
      dehydrogenase from Bacillus subtilis (BsGDH).

PMID- 24113813
TI  - Successes of a national study of the Chronic Disease Self-Management Program:
      meeting the triple aim of health care reform.
AB  - BACKGROUND: Emerging health care reform initiatives are of growing importance
      amidst concerns about providing care to increasing numbers of adults with
      multiple chronic conditions. Evidence-based self-management strategies are
      recognized as central to managing a variety of chronic diseases by improving the
      medical, emotional, and social role management demands of chronic conditions.
      OBJECTIVES: To examine the effectiveness of the Chronic Disease Self-Management
      Program (CDSMP) among a national sample of participants organized around the
      Triple Aim goals of better health, better health care, and better value in terms
      of reduced health care utilization. RESEARCH DESIGN: Utilizing data collected
      from small-group CDSMP workshops, baseline, 6-month, and 12-month assessments
      were examined using 3 types of mixed-effects models to provide unbiased estimates
      of intervention effects. SUBJECTS: Data were analyzed from 1170 community
      dwelling CDSMP participants. MEASURES: Triple Aim-related outcome measures:
      better health (eg, self-reported health, pain, fatigue, depression), better
      health care (eg, patient-physician communication, medication compliance,
      confidence completing medical forms), and better value [eg, reductions in
      emergency room (ER) visits and hospitalizations in the past 6 mo]. RESULTS:
      Significant improvements for all better health and better health care outcome
      measures were observed from baseline to 12-month follow-up. The odds of ER visits
      significantly reduced from baseline to 12-month follow-up, whereas significant
      reductions in hospitalization were only observed from baseline to 6-month follow
      up. CONCLUSIONS: This National Study of CDSMP (National Study) demonstrates the
      successful translation of CDSMP into widespread practice and its potential for
      helping the nation achieve the triple aims of health care reform.

PMID- 24113814
TI  - Response to letter with regard to our paper "Engagement with automated patient
      monitoring and self-management support calls": experience with a thousand
      chronically ill patients.

PMID- 24113815
TI  - Delayed and unmet need for medical care among publicly insured adults with
      disabilities.
AB  - BACKGROUND: While Medicaid is an important source of insurance coverage for
      persons with disabilities, barriers remain to accessing care for this population.
      OBJECTIVES: This study addresses 3 research questions: (1) do adults with
      disabilities experience greater unmet need/delayed care?; (2) do barriers related
      to cost, providers, or structure vary by disability status?; and (3) do barriers
      mediate the relationship between disability and access to care? RESEARCH DESIGN:
      Data were obtained from a 2008 stratified random sample of Minnesota Health Care
      Program's nonelderly adult enrollees (n=1880). The survey was administered by
      mail, with a telephone follow-up for nonresponders. MEASURES: Disability is
      defined by self-report. Access to care is measured by reported delayed and unmet
      need for medical care within the past year. Respondents were asked about their
      experiences with a variety of cost-related, provider-related, and structural
      barriers to care. RESULTS: Respondents with a disability were more likely to
      experience delayed (40%) and unmet need (23%) for medical care than persons
      without disabilities (24% and 10%, respectively). Persons with disabilities also
      reported multiple barriers to health care, especially structural barriers, such
      as making a timely appointment and accessing transportation (74% vs. 59%). The
      greater likelihood of facing a structural barrier partially explained increased
      risk of delayed or unmet care among adults with disabilities. CONCLUSIONS:
      Disparities in access to health care based on disability status remain even for
      persons who have insurance. These disparities deserve further research and policy
      attention to better address the particular needs of this population.

PMID- 24113816
TI  - Bending the cost curve? Results from a comprehensive primary care payment pilot.
AB  - BACKGROUND: There is much interest in understanding how using bundled primary
      care payments to support a patient-centered medical home (PCMH) affects total
      medical costs. RESEARCH DESIGN AND SUBJECTS: We compare 2008-2010 claims and
      eligibility records on about 10,000 patients in practices transforming to a PCMH
      and receiving risk-adjusted base payments and bonuses, with similar data on
      approximately 200,000 patients of nontransformed practices remaining under fee
      for-service reimbursement. METHODS: We estimate the treatment effect using
      difference-in-differences, controlling for trend, payer type, plan type, and
      fixed effects. We weight to account for partial-year eligibility, use propensity
      weights to address differences in exogenous variables between control and
      treatment patients, and use the Massachusetts Health Quality Project algorithm to
      assign patients to practices. RESULTS: Estimated treatment effects are sensitive
      to: control variables, propensity weighting, the algorithm used to assign
      patients to practices, how we address differences in health risk, and whether/how
      we use data from enrollees who join, leave, or change practices. Unadjusted PCMH
      spending reductions are 1.5% in year 1 and 1.8% in year 2. With fixed patient
      assignment and other adjustments, medical spending in the treatment group seems
      to be 5.8% (P=0.20) lower in year 1 and 8.7% (P=0.14) lower in year 2 than for
      propensity-weighted, continuously enrolled controls; the largest proportional 2
      year reduction in spending occurs in laboratory test use (16.5%, P=0.02).
      CONCLUSIONS: Although estimates are imprecise because of limited data and quasi
      experimental design, risk-adjusted bundled payment for primary care may have
      dampened spending growth in 3 practices implementing a PCMH.

PMID- 24113817
TI  - Alterations of the enteric smooth musculature in diverticular disease.
AB  - BACKGROUND: The pathogenesis of diverticular disease (DD) is considered to be
      multifactorial and involves intestinal motor disturbances and an underlying
      enteric neuromuscular pathology. While an enteric neuropathy has been well
      documented, actual studies on concomitant alterations of the enteric musculature
      are limited. This study is aimed at reassessing the smooth muscle tissue by
      histological, ultrastructural and molecular-biological approaches. METHODS: Full
      thickness sigmoid specimens were obtained from patients with DD (n = 20) and
      controls (n = 19). Morphometric analysis was performed to evaluate the thickness
      and connective tissue index of the circular and longitudinal muscle layers as
      well as the myenteric plexus. Structural alterations were determined by light and
      transmission electron microscopy. mRNA profiles of components of the contractile
      smooth muscle apparatus including smooth muscle alpha-actin, smoothelin, histone
      deacetylase 8, and smooth muscle myosin heavy chain (SMMHC) were assessed by
      qPCR. Altered gene expression levels were confirmed at protein level by
      immunohistochemistry. RESULTS: Compared to controls, patients with DD showed (1)
      increased thickness of the circular and longitudinal muscle layers, (2)
      architectural alterations of smooth muscle cells, (3) increased connective tissue
      index of the longitudinal muscle layer, (4) focally reduced density of
      myofilaments at ultrastructural level, (5) specific down-regulation of SMMHC mRNA
      levels, (6) decreased immunoreactivity of SMMHC, (7) oligo-neuronal
      hypoganglionosis. CONCLUSIONS: DD is associated with distinct structural and
      functional alterations of the enteric musculature. The enteric myopathy is
      characterized by disturbed muscular architecture, connective tissue replacement
      and loss of specific myofilaments and thus may contribute to the pathogenesis and
      progression of DD.

PMID- 24113818
TI  - Impact of hospital volume on outcomes in acute pancreatitis: a study using a
      nationwide administrative database.
AB  - BACKGROUND: Although several population-based studies have shown higher hospital
      volume (HV) to be associated with better outcomes in acute pancreatitis, they
      failed to adjust for disease severity and did not take into account the
      potentially non-linear relationship between HV and outcomes. Using a Japanese
      nationwide administrative database, this study aimed to evaluate the volume
      outcome relationship in acute pancreatitis by means of statistical methods that
      permitted such considerations. METHODS: In-hospital mortality, length of stay,
      and total costs for patients with acute pancreatitis were analyzed using
      multivariate regression models fitted with generalized estimating equations.
      Adjustment for severity was based on the Japanese Severity Scoring System and
      other patient characteristics. We used restricted cubic spline functions to
      examine the potential non-linear relationships between HV and outcomes. RESULTS:
      In all, 17,415 eligible patients with acute pancreatitis were identified from
      1,032 hospitals between 1 July 2010 and 30 September 2011. The in-hospital
      mortality rate was 2.6 %, and the median total costs were US $7,740
      (interquartile range, 5,150-11,920). The overall and non-linear volume-outcome
      relationships were not significant either for in-hospital mortality or total
      costs. The median length of stay was 14 days (interquartile range, 10-22), and
      high HV was positively associated with shorter hospitalization (overall, P <
      0.001; non-linear, P = 0.194). CONCLUSIONS: Despite the shorter hospitalization
      with higher HV, no inverse volume-outcome relationship was evident for acute
      pancreatitis. Further evidence is required to justify the volume-based selective
      referral of acute pancreatitis patients.

PMID- 24113820
TI  - SYBR(r)Green qPCR Salmonella detection system allowing discrimination at the
      genus, species and subspecies levels.
AB  - In this work, a three-level Salmonella detection system based on a combination of
      seven SYBR(r)Green qPCR was developed. This detection system discriminates
      Salmonella at the genus, species and subspecies levels using a single 96-well
      plate. The SYBR(r)Green qPCR assays target the invA, rpoD, iroB and safC genes,
      as well as the STM0296 locus, putatively coding for a cytoplasmic protein. This
      study includes the design of primer pairs, in silico and in situ selectivity,
      sensitivity, repeatability and reproducibility evaluations of the seven
      SYBR(r)Green qPCR assays. Each detection level displayed a selectivity of 100 %.
      This combinatory SYBR(r)Green qPCR system was also compared with three
      commercially available Salmonella qPCR detection kits. This comparison
      highlighted the importance of using a multi-gene detection system to be able to
      detect every target strain, even those with deletion or mutation of important
      genes. 

PMID- 24113819
TI  - Classification of posterior polymorphous corneal dystrophy as a corneal ectatic
      disorder following confirmation of associated significant corneal steepening.
AB  - IMPORTANCE: The identification of steep corneal curvatures in a significant
      percentage of patients with posterior polymorphous corneal dystrophy (PPCD)
      confirms this previously reported association and suggests a role for the ZEB1
      protein in keratocyte function. OBJECTIVE: To determine whether PPCD is
      characterized by significant corneal steepening. DESIGN, SETTING, AND
      PARTICIPANTS: Cross-sectional study at university-based and private ophthalmology
      practices of 38 individuals (27 affected and 11 unaffected) from 23 families with
      PPCD. EXPOSURE: Slitlamp examination and corneal topographic imaging were
      performed for individuals with PPCD and unaffected family members. Saliva or
      blood samples were obtained from each individual for DNA isolation and ZEB1
      sequencing. Corneal ZEB1 expression was measured using immunohistochemistry. MAIN
      OUTCOMES AND MEASURES: Percentage of individuals affected with PPCD and controls
      with an average keratometric value greater than 48.0 diopters (D) in each eye;
      the mean keratometric value averaged for both eyes of individuals with PPCD and
      controls; and the correlation of ZEB1 mutation with keratometric value. RESULTS:
      ZEB1 coding region mutations were identified in 7 of the 27 affected individuals.
      Ten of the 38 individuals (26.3%) had average keratometric values greater than
      48.0 D OU: 10 of 27 individuals with PPCD (37.0%; 6 of 7 individuals with ZEB1
      mutations [85.7%] and 4 of 20 individuals without ZEB1 mutations [20.0%]) and 0
      of 11 unaffected individuals (P = .04 for unaffected vs affected individuals; P =
      .004 for individuals with PPCD with vs without ZEB1 mutation). The mean
      keratometric value of each eye of affected individuals (48.2 D) was significantly
      greater than that of each eye of unaffected family members (44.1 D) (P = .03).
      Affected individuals with ZEB1 mutations demonstrated a mean keratometric value
      of 53.3 D, which was significantly greater than that of affected individuals
      without ZEB1 mutations (46.5 D; P = .004). Fluorescence immunohistochemistry
      demonstrated ZEB1 expression in keratocyte nuclei. CONCLUSIONS AND RELEVANCE:
      Abnormally steep corneal curvatures are identified in 37% of all individuals with
      PPCD and 86% of affected individuals with PPCD secondary to ZEB1 mutations. ZEB1
      is present in keratocyte nuclei, suggesting a role for ZEB1 in keratocyte
      function. Therefore, ZEB1 may play a role in both corneal stromal and endothelial
      development and function, and PPCD should be considered both an endothelial
      dystrophy and an ectatic disorder.

PMID- 24113821
TI  - Characterization of soybean beta-expansin genes and their expression responses to
      symbiosis, nutrient deficiency, and hormone treatment.
AB  - Expansins are plant cell wall-loosening proteins encoded by a superfamily of
      genes including alpha-expansin, beta-expansin, expansin-like A, and expansin-like
      B proteins. They play a variety of biological roles during plant growth and
      development. Expansin genes have been reported in many plant species, and results
      primarily from graminaceous members indicate that beta-expansins are more
      abundant in monocots than in dicots. Soybean [Glycine max (L.) Merr] is an
      important legume crop. This work identified nine beta-expansin gene family
      members in soybean (GmEXPBs) that were divided into two distinct classes based on
      phylogeny and gene structure, with divergence between the two groups occurring
      more in introns than in exons. A total of 887 hormone-responsive and
      environmental stress-related putative cis-elements from 188 families were found
      in the 2-kb upstream region of GmEXPBs. Variations in number and type of cis
      elements associated with each gene indicate that the function of these genes is
      differentially regulated by these signals. Expression analysis confirmed that the
      family members were ubiquitously, yet differentially expressed in soybean.
      Responsiveness to nutrient deficiency stresses and regulation by auxin (indole-3
      acetic acid) and cytokinin (6-benzylaminopurine) varied among GmEXPBs. In
      addition, most beta-expansin genes were associated with symbiosis of soybean
      inoculated with Rhizobium or abuscular mycorrhizal fungi (AMF). Taken together,
      these results systematically investigate the characteristics of the entire GmEXPB
      family in soybean and comprise the first report analyzing the relationship of
      GmEXPBs with rhizobial or AMF symbiosis. This information is a valuable step in
      the process of understanding the expansin protein functions in soybean and opens
      avenues for continued researches.

PMID- 24113822
TI  - Novel multispecies microbial consortia involved in lignocellulose and 5
      hydroxymethylfurfural bioconversion.
AB  - To develop a targeted metagenomics approach for the analysis of novel
      multispecies microbial consortia involved in the bioconversion of lignocellulose
      and furanic compounds, we applied replicated sequential batch aerobic enrichment
      cultures with either pretreated or untreated wheat straw as the sources of carbon
      and energy. After each transfer, exponential growth of bacteria was detected
      using microscopic cell counts, indicating that the substrate was being utilized.
      In batch, the final bacterial abundances increased from an estimated 5 to 8.7-9.5
      log 16S rRNA gene copy numbers/ml. The abundances of fungal propagules showed
      greater variation, i.e., between 5.4 and 8.0 log ITS1 copies/ml. Denaturing
      gradient gel electrophoresis analyses showed that the bacterial consortia in both
      treatments reached approximate structural stability after six transfers.
      Moreover, the structures of the fungal communities were strongly influenced by
      substrate treatment. A total of 124 bacterial strains were isolated from the two
      types of enrichment cultures. The most abundant strains were affiliated with the
      genera Raoultella/Klebsiella, Kluyvera, Citrobacter, Enterobacter, Pseudomonas,
      Acinetobacter, Flavobacterium and Arthrobacter. Totals of 43 and 11 strains
      obtained from the untreated and pretreated substrates, respectively, showed
      (hemi)cellulolytic activity (CMC-ase and xylanase), whereas 96 strains were
      capable of growth in 7.5 mM 5-hydroxymethylfurfural. About 50 % of the latter
      showed extracellular oxidoreductase activity as detected by a novel iodide
      oxidation method. Also, (hemi)cellulolytic fungal strains related to Coniochaeta,
      Plectosphaerella and Penicillium were isolated. One Trichosporon strain was
      isolated from pretreated wheat straw. The two novel bacterial-fungal consortia
      are starting points for lignocellulose degradation applications.

PMID- 24113823
TI  - Current knowledge on mycolic acids in Corynebacterium glutamicum and their
      relevance for biotechnological processes.
AB  - Corynebacterium glutamicum is the world's largest producer of glutamate and
      lysine. Industrial glutamate overproduction is induced by empirical processes,
      such as biotin limitation, supplementation with specific surfactants or addition
      of sublethal concentration of certain antibiotics to the culture media. Although
      Gram-positive bacteria, C. glutamicum and related bacterial species and genera
      contain, in addition to the plasma membrane, an outer permeability membrane
      similar to that of Gram-negative microorganisms. As the amino acids have to cross
      both membranes, their integrity, composition and fluidity influence the export
      process. While the precise mechanism of the export of the amino acids by C.
      glutamicum is not fully understood, the excretion of amino acids through the
      inner membrane involved at least a major export system mechanosensitive channel
      MscS family (MscCG) encoded by NCgl1221. As the various industrial treatments
      have been shown to affect the lipid content of the bacterial cell, it is strongly
      believed that defects in the hallmark of the outer membrane, 2-alkyl, 3
      hydroxylated long-chain fatty acids (mycolic acids), could be key factors in the
      glutamate overproduction. This review aims at giving an overview of the current
      knowledge on mycolic acids structure, biosynthesis and transfer in C. glutamicum
      and their relevance for amino acid biotechnological production. 

PMID- 24113824
TI  - Caecal fermentation, putrefaction and microbiotas in rats fed milk casein, soy
      protein or fish meal.
AB  - To clarify the effect of soy protein (SP) and fish meal (FM), compared to milk
      casein (MC), on the intestinal environment, we examined caecal environment of
      rats fed the test diets. Four-week-old rats were fed AIN-76-based diet containing
      20 %, w/w MC, SP or FM for 16 days. Caecal organic acids were analysed by HPLC.
      Caecal putrefactive compounds (indole, phenol, H2S and ammonia) were analysed by
      colorimetric assays. Caecal microflora was determined by 16S rRNA gene-DGGE and
      pyrosequencing with bar-coded primers targeting the bacterial 16S rRNA gene. n
      Butyric and lactic acid levels were high in rats fed SP and FM, respectively.
      Butyrate-producing bacteria, such as Oscillibacter, and lactate-producing
      bacteria, such as Lactobacillus, were detected in each diet group. Also, the
      putrefactive compound contents were high in rats fed SP and FM. In this study,
      both DGGE and pyrosequencing analyses were able to evaluate the dynamics of the
      intestinal microbiota. The results indicate that dietary proteins can alter the
      intestinal environment, affecting fermentation by the intestinal microbiota and
      the generation of putrefactive compounds.

PMID- 24113825
TI  - Penicillium decumbens BrlA extensively regulates secondary metabolism and
      functionally associates with the expression of cellulase genes.
AB  - Penicillium decumbens has been used in the industrial production of
      lignocellulolytic enzymes in China for more than 15 years. Conidiation is
      essential for most industrial fungi because conidia are used as starters in the
      first step of fermentation. To investigate the mechanism of conidiation in P.
      decumbens, we generated mutants defective in two central regulators of
      conidiation, FluG and BrlA. Deletion of fluG resulted in neither "fluffy"
      phenotype nor alteration in conidiation, indicating possible different upstream
      mechanisms activating brlA between P. decumbens and Aspergillus nidulans.
      Deletion of brlA completely blocked conidiation. Further investigation of brlA
      expression in different media (nutrient-rich or nutrient-poor) and different
      culture states (liquid or solid) showed that brlA expression is required but not
      sufficient for conidiation. The brlA deletion strain exhibited altered hyphal
      morphology with more branches. Genome-wide expression profiling identified BrlA
      dependent genes in P. decumbens, including genes previously reported to be
      involved in conidiation as well as previously reported chitin synthase genes and
      acid protease gene (pepB). The expression levels of seven secondary metabolism
      gene clusters (from a total of 28 clusters) were drastically regulated in the
      brlA deletion strain, including a downregulated cluster putatively involved in
      the biosynthesis of the mycotoxins roquefortine C and meleagrin. In addition, the
      expression levels of most cellulase genes were upregulated in the brlA deletion
      strain detected by real-time quantitative PCR. The brlA deletion strain also
      exhibited an 89.1 % increase in cellulase activity compared with the wild-type
      strain. The results showed that BrlA in P. decumbens not only has a key role in
      regulating conidiation, but it also regulates secondary metabolism extensively as
      well as the expression of cellulase genes.

PMID- 24113826
TI  - The role of coproporphyrinogen III oxidase and ferrochelatase genes in heme
      biosynthesis and regulation in Aspergillus niger.
AB  - Heme is a suggested limiting factor in peroxidase production by Aspergillus spp.,
      which are well-known suitable hosts for heterologous protein production. In this
      study, the role of genes coding for coproporphyrinogen III oxidase (hemF) and
      ferrochelatase (hemH) was analyzed by means of deletion and overexpression to
      obtain more insight in fungal heme biosynthesis and regulation. These enzymes
      represent steps in the heme biosynthetic pathway downstream of the siroheme
      branch and are suggested to play a role in regulation of the pathway. Based on
      genome mining, both enzymes deviate in cellular localization and protein domain
      structure from their Saccharomyces cerevisiae counterparts. The lethal phenotype
      of deletion of hemF or hemH could be remediated by heme supplementation
      confirming that Aspergillus niger is capable of hemin uptake. Nevertheless, both
      gene deletion mutants showed an extremely impaired growth even with hemin
      supplementation which could be slightly improved by media modifications and the
      use of hemoglobin as heme source. The hyphae of the mutant strains displayed
      pinkish coloration and red autofluorescence under UV indicative of cellular
      porphyrin accumulation. HPLC analysis confirmed accumulation of specific
      porphyrins, thereby confirming the function of the two proteins in heme
      biosynthesis. Overexpression of hemH, but not hemF or the aminolevulinic acid
      synthase encoding hemA, modestly increased the cellular heme content, which was
      apparently insufficient to increase activity of endogenous peroxidase and
      cytochrome P450 enzyme activities. Overexpression of all three genes increased
      the cellular accumulation of porphyrin intermediates suggesting regulatory
      mechanisms operating in the final steps of the fungal heme biosynthesis pathway. 

PMID- 24113827
TI  - Construction and characterization of a novel chimeric antibody c3C7 specific for
      the integrin alphaIIbbeta3 complex.
AB  - A murine monoclonal antibody (mAb) 3C7 against integrin alphaIIbbeta3 was
      previously obtained as a potential antithrombotic agent in our laboratory. The
      epitope of 3C7 is a specific conformation of the alphaIIbbeta3 complex, but not
      either of the two subunits, which makes it different from abciximab, a
      supplementary antibody drug used in percutaneous coronary intervention which has
      a cross-reaction with other integrins sharing the beta3 subunit. To reduce the
      human anti-mouse antibody reactions of 3C7, the variable regions of this antibody
      were cloned and fused with the constant counterparts of human IgG1. Two vectors
      of light and heavy chains were constructed and co-transfected into CHO-dhfr(-)
      cells. The chimeric antibody c3C7 was purified and the properties of c3C7 were
      compared with 3C7. Identical to its parent antibody 3C7, c3C7 binds to the
      alphaIIbbeta3 complex, but not to either of the subunits. The K(d) value of c3C7
      was in the same order of magnitude as 3C7 (1.570 +/- 0.326 vs 0.780 +/- 0.182
      nmol/L). Human platelet aggregation induced by adenosine diphosphate was
      effectively inhibited by c3C7 in a dose-dependent manner. In conclusion, after
      the modification, c3C7 retained the properties of its parent mAb with no loss of
      its biological activity. Therefore, c3C7 has the potential to become a novel
      agent for the treatment of thrombosis.

PMID- 24113828
TI  - Metabolic engineering of Escherichia coli for biosynthesis of poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) from glucose.
AB  - The Escherichia coli XL1-blue strain was metabolically engineered to synthesize
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] through 2
      ketobutyrate, which is generated via citramalate pathway, as a precursor for
      propionyl-CoA. Two different metabolic pathways were examined for the synthesis
      of propionyl-CoA from 2-ketobutyrate. The first pathway is composed of the
      Dickeya dadantii 3937 2-ketobutyrate oxidase or the E. coli pyruvate oxidase
      mutant (PoxB L253F V380A) for the conversion of 2-ketobutyrate into propionate
      and the Ralstonia eutropha propionyl-CoA synthetase (PrpE) or the E. coli acetyl
      CoA:acetoacetyl-CoA transferase for further conversion of propionate into
      propionyl-CoA. The second pathway employs pyruvate formate lyase encoded by the
      E. coli tdcE gene or the Clostridium difficile pflB gene for the direct
      conversion of 2-ketobutyrate into propionyl-CoA. As the direct conversion of 2
      ketobutyrate into propionyl-CoA could not support the efficient production of
      P(3HB-co-3HV) from glucose, the first metabolic pathway was further examined.
      When the recombinant E. coli XL1-blue strain equipped with citramalate pathway
      expressing the E. coli poxB L253F V380A gene and R. eutropha prpE gene together
      with the R. eutropha PHA biosynthesis genes was cultured in a chemically defined
      medium containing 20 g/L of glucose as a sole carbon source, P(3HB-co-2.3 mol%
      3HV) was produced up to the polymer content of 61.7 wt.%. Moreover, the 3HV
      monomer fraction in P(3HB-co-3HV) could be increased up to 5.5 mol% by additional
      deletion of the prpC and scpC genes, which are responsible for the metabolism of
      propionyl-CoA in host strains.

PMID- 24113829
TI  - Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a
      mouse model of auditory neuropathy.
AB  - Ouabain application to the round window can selectively destroy type-I spiral
      ganglion cells, producing an animal model of auditory neuropathy. To assess the
      long-term effects of this deafferentation on synaptic organization in the organ
      of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show
      any post-injury plasticity in the adult, we quantified the peripheral and central
      synapses of type-I neurons at posttreatment times ranging from 1 to 3 months.
      Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs)
      confirmed the neuropathy phenotype. Counts of presynaptic ribbons and
      postsynaptic glutamate receptor patches in the inner hair cell area decreased
      with post-exposure time, as did counts of cochlear nerve terminals in the
      cochlear nucleus. Although these counts provided no evidence of new synapse
      formation via branching from surviving neurons, the regular appearance of ectopic
      neurons in the inner hair cell area suggested that neurite extension is not
      uncommon. Correlations between pathophysiology and histopathology showed that ABR
      thresholds are very insensitive to even massive neural degeneration, whereas the
      amplitude of ABR wave 1 is a better metric of synaptic degeneration.

PMID- 24113831
TI  - Jack-of-all-trades master of all? Snake vertebrae have a generalist inner
      organization.
AB  - Snakes are a very speciose group of squamates that adapted to various habitats
      and ecological niches. Their ecological diversity is of particular interest and
      functional demands associated with their various styles of locomotion are
      expected to result in anatomical specializations. In order to explore the
      potential adaptation of snakes to their environment we here analyze variation in
      vertebral structure at the microanatomical level in species with different
      locomotor adaptations. Vertebrae, being a major element of the snake body, are
      expected to display adaptations to the physical constraints associated with the
      different locomotor modes and environments. Our results revealed a rather
      homogenous vertebral microanatomy in contrast to what has been observed for other
      squamates and amniotes more generally. We here suggest that the near-absence of
      microanatomical specializations in snake vertebrae might be correlated to their
      rather homogeneous overall morphology and reduced range of morphological
      diversity, as compared to lizards. Thus, snakes appear to retain a generalist
      inner morphology that allows them to move efficiently in different environments.
      Only a few ecologically highly specialized taxa appear to display some
      microanatomical specializations that remain to be studied in greater detail. 

PMID- 24113832
TI  - High-efficiency localization of Na(+)-K(+) ATPases on the cytoplasmic side by
      direct stochastic optical reconstruction microscopy.
AB  - We describe a concise and effective strategy towards precisely mapping Na(+)-K(+)
      ATPases on the cytoplasmic side of cell membranes by direct stochastic optical
      reconstruction microscopy (dSTORM). We found that most Na(+)-K(+) ATPases are
      localized in different sizes of clusters on human red blood cell (hRBC)
      membranes, revealed by Ripley's K-function analysis. Further evidence that
      cholesterol depletion causes the dispersion of Na(+)-K(+) ATPase clusters
      indicates that such clusters could be localized in cholesterol-enriched domains.
      Our results suggest that Na(+)-K(+) ATPases might aggregate within the lipid
      rafts to fulfill their functions. 

PMID- 24113833
TI  - Single-balloon enteroscopy: a single-center experience of 48 procedures.
AB  - The aim of this study was to report the analysis of a single-center experience
      with single-balloon enteroscopy (SBE). A retrospective analysis of patients with
      small-bowel disorder who underwent SBE procedure from February 2011 to February
      2013 was carried out. A total of 40 patients underwent 48 SBE procedures.
      Antegrade and retrograde approaches were used in 68.8 % and 31.2 % of subjects,
      respectively. The main indications were obscure gastrointestinal bleeding (n =
      28), chronic diarrhea (n = 6), and chronic abdominal pain (n = 6). Average (SD)
      insertion length by antegrade approach was 150.6 (31.4) cm (range 90-210 cm)
      beyond the duodenojejunal flexure and by retrograde approach was 106.6 (29.4) cm
      (range 40-140 cm) proximal to the ileocecal junction. Average procedure time for
      antegrade approach was 46.3 (9.0) min (range 25-60 min) and for retrograde
      approach was 61.3 (12.8) min (range 45-90 min). Panendoscopy was not possible in
      any of the eight patients in whom antegrade and retrograde approaches were
      performed. Overall diagnostic yield was 55 % and therapeutic procedures were done
      in 20 % of patients. There were no significant complications. SBE is a safe and
      effective method to diagnose patients with small-bowel disease and provides a
      useful tool for intervention.

PMID- 24113834
TI  - Professor N. Rangabashyam (1933-2013).

PMID- 24113835
TI  - Risk stratification in arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic
      cardiomyopathy characterized by myocyte death and fibrofatty replacement mostly
      in the right ventricle. It is a leading cause of sudden cardiac death (SCD) in
      individuals under the age of 35 years. The main goal in the treatment of the
      disease is the prevention of SCD. An implantable cardioverter-defibrillator (ICD)
      is the only proven life-saving therapeutic option able to improve survival in
      ARVC patients. This therapy is not free from side effects and it accounts for a
      relatively high rate of morbidity because of the occurrence of inappropriate ICD
      interventions and of complications, both at implantation and during the follow
      up. In recent years, the approach to ICD implantation has been changing on the
      basis of new emerging data on risk stratification. The usefulness of ICD
      implantation for secondary prevention has been definitively proven; the most
      challenging question is how to treat patients with no history of previous cardiac
      arrest or hemodynamically unstable ventricular tachycardia (VT). The value of ECG
      abnormalities, syncope, VT, and right/left ventricular involvement as predictors
      of SCD has been assessed in different studies with the purpose of better defining
      risk stratification in ARVC. Nevertheless, in spite of the growing amount of
      data, primary prevention in ARVC patients remains mostly an individual decision.

PMID- 24113830
TI  - Metabolic targets for cancer therapy.
AB  - Malignant cells exhibit metabolic changes, when compared to their normal
      counterparts, owing to both genetic and epigenetic alterations. Although such a
      metabolic rewiring has recently been indicated as yet another general hallmark of
      cancer, accumulating evidence suggests that the metabolic alterations of each
      neoplasm represent a molecular signature that intimately accompanies and allows
      for different facets of malignant transformation. During the past decade,
      targeting cancer metabolism has emerged as a promising strategy for the
      development of selective antineoplastic agents. Here, we discuss the intimate
      relationship between metabolism and malignancy, focusing on strategies through
      which this central aspect of tumour biology might be turned into cancer's
      Achilles heel.

PMID- 24113836
TI  - Boron functionalization of BODIPY by various alcohols and phenols.
AB  - The synthesis of new B-O BODIPY derivatives functionalized with different alkoxy
      or diarylalkoxy derivatives is described. These compounds were synthesized from
      the reaction of different B-F BODIPY precursors with various alcohols and
      phenols, in the presence of AlCl3. Water-soluble dyes could be synthesized as
      well with this method, specifically by the introduction of polyethyleneglycol
      (PEG) groups. A photophysical study of the different compounds was performed, and
      showed that the B-O BODIPY derivatives exhibit rich fluorescence properties.
      Finally, the conjugation of the BODIPY core has been extended using two distyryl
      groups, hence providing NIR emitting BODIPY derivatives, in which one or two PEG
      groups have been anchored, making these systems very promising for future medical
      imaging applications. 

PMID- 24113837
TI  - Osteoporosis in the European Union: medical management, epidemiology and economic
      burden. A report prepared in collaboration with the International Osteoporosis
      Foundation (IOF) and the European Federation of Pharmaceutical Industry
      Associations (EFPIA).
AB  - This report describes the epidemiology, burden, and treatment of osteoporosis in
      the 27 countries of the European Union (EU27). INTRODUCTION: Osteoporosis is
      characterized by reduced bone mass and disruption of bone architecture, resulting
      in increased risk of fragility fractures which represent the main clinical
      consequence of the disease. Fragility fractures are associated with substantial
      pain and suffering, disability and even death for affected patients and
      substantial costs to society. The aim of this report was to characterize the
      burden of osteoporosis in the EU27 in 2010 and beyond. METHODS: The literature on
      fracture incidence and costs of fractures in the EU27 was reviewed and
      incorporated into a model estimating the clinical and economic burden of
      osteoporotic fractures in 2010. RESULTS: Twenty-two million women and 5.5 million
      men were estimated to have osteoporosis; and 3.5 million new fragility fractures
      were sustained, comprising 610,000 hip fractures, 520,000 vertebral fractures,
      560,000 forearm fractures and 1,800,000 other fractures (i.e. fractures of the
      pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral
      fractures). The economic burden of incident and prior fragility fractures was
      estimated at <euro> 37 billion. Incident fractures represented 66 % of this cost,
      long-term fracture care 29 % and pharmacological prevention 5 %. Previous and
      incident fractures also accounted for 1,180,000 quality-adjusted life years lost
      during 2010. The costs are expected to increase by 25 % in 2025. The majority of
      individuals who have sustained an osteoporosis-related fracture or who are at
      high risk of fracture are untreated and the number of patients on treatment is
      declining. CONCLUSIONS: In spite of the high social and economic cost of
      osteoporosis, a substantial treatment gap and projected increase of the economic
      burden driven by the aging populations, the use of pharmacological interventions
      to prevent fractures has decreased in recent years, suggesting that a change in
      healthcare policy is warranted.

PMID- 24113838
TI  - Osteoporosis in the European Union: a compendium of country-specific reports.
AB  - This report describes epidemiology, burden, and treatment of osteoporosis in each
      of the 27 countries of the European Union (EU27). INTRODUCTION: In 2010, 22
      million women and 5.5 million men were estimated to have osteoporosis in the EU;
      and 3.5 million new fragility fractures were sustained, comprising 620,000 hip
      fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000
      other fractures. The economic burden of incident and prior fragility fractures
      was estimated at ? 37 billion. Previous and incident fractures also accounted for
      1,180,000 quality-adjusted life years lost during 2010. The costs are expected to
      increase by 25 % in 2025. The majority of individuals who have sustained an
      osteoporosis-related fracture or who are at high risk of fracture are untreated
      and the number of patients on treatment is declining. The aim of this report was
      to characterize the burden of osteoporosis in each of the EU27 countries in 2010
      and beyond. METHODS: The data on fracture incidence and costs of fractures in the
      EU27 were taken from a concurrent publication in this journal (Osteoporosis in
      the European Union: Medical Management, Epidemiology and Economic Burden) and
      country specific information extracted. RESULTS: The clinical and economic burden
      of osteoporotic fractures in 2010 is given for each of the 27 countries of the
      EU. The costs are expected to increase on average by 25 % in 2025. The majority
      of individuals who have sustained an osteoporosis-related fracture or who are at
      high risk of fracture are untreated and the number of patients on treatment is
      declining. CONCLUSIONS: In spite of the high cost of osteoporosis, a substantial
      treatment gap and projected increase of the economic burden driven by aging
      populations, the use of pharmacological prevention of osteoporosis has decreased
      in recent years, suggesting that a change in healthcare policy concerning the
      disease is warranted.

PMID- 24113840
TI  - Mercury dynamics in groundwater across three distinct riparian zone types of the
      US Midwest.
AB  - Although the intense biogeochemical gradients present in riparian zones have the
      potential to affect mercury (Hg) cycling, Hg dynamics in riparian zones has
      received relatively little attention in the literature. Our study investigated
      groundwater filtered total mercury (THg) and methylmercury (MeHg) dynamics in
      three riparian zones with contrasting hydrogeomorphic (HGM) characteristics
      (till, alluvium, outwash) in the US Midwest. Despite high Hg deposition rates
      (>16 MUg m(-2)) in the region, median THg (<1.05 ng L(-1)) and MeHg (<0.05 ng L(
      1)) concentrations were low at the study sites. Methylmercury concentrations were
      significantly (p < 0.05) correlated to THg (R = 0.82), temperature (R = 0.55),
      and dissolved organic carbon (DOC) (R = 0.62). THg also correlated with
      groundwater DOC (R = 0.59). The proportion of MeHg in THg (%MeHg) was
      significantly correlated to temperature (R = 0.58) and MeHg (R = 0.50). Results
      suggest that HGM characteristics, the presence of tile drains, and the propensity
      for overbank flooding at a riparian site determined the extent to which stream
      water Hg concentrations influenced riparian groundwater Hg levels or vice versa.
      Differences in hydrogeomorphic characteristics between sites did not translate
      however in significant differences in groundwater MeHg or %MeHg. Overall,
      widespread Hg contamination in the most common riparian hydrogeomorphic types of
      the US Midwest is unlikely to be a major concern. However, for frequently flooded
      riparian zones located downstream from a potentially large source of Hg (e.g.,
      concentrated urban development), Hg concentrations are likely to be higher than
      at other sites. 

PMID- 24113839
TI  - Longitudinal relationships between whole body and central adiposity on weight
      bearing bone geometry, density, and bone strength: a pQCT study in young girls.
AB  - Longitudinal relationships between adiposity (total body and central) and bone
      development were assessed in young girls. Total body and android fat masses were
      positively associated with bone strength and density parameters of the femur and
      tibia. These results suggest adiposity may have site-specific stimulating effects
      on the developing bone. INTRODUCTION: Childhood obesity may impair bone
      development, but the relationships between adiposity and bone remain unclear.
      Failure to account for fat pattern may explain the conflicting results. PURPOSE:
      Longitudinal associations of total body fat mass (TBFM) and android fat mass
      (AFM) with 2-year changes in weight-bearing bone parameters were examined in 260
      girls aged 8-13 years at baseline. Peripheral quantitative computed tomography
      was used to measure bone strength index (BSI, square milligrams per quartic
      millimeter), strength-strain index (SSI, cubic millimeters), and volumetric bone
      mineral density (vBMD, milligrams per cubic centimeter) at distal metaphyseal and
      diaphyseal regions of the femur and tibia. TBFM and AFM were assessed by dual
      energy x-ray absorptiometry. RESULTS: Baseline TBFM and AFM were positively
      associated with the change in femur BSI (r = 0.20, r = 0.17, respectively) and
      femur trabecular vBMD (r = 0.19, r = 0.19, respectively). Similarly, positive
      associations were found between TBFM and change in tibia BSI and SSI (r = 0.16, r
      = 0.15, respectively), and femur total and trabecular vBMD (r = 0.12, r = 0.14,
      respectively). Analysis of covariance showed that girls in the middle thirds of
      AFM had significantly lower femur trabecular vBMD and significantly higher tibia
      cortical vBMD than girls in the highest thirds of AFM. All results were
      significant at p < 0.05. CONCLUSIONS: Whereas baseline levels of TBFM and AFM are
      positive predictors of bone strength and density at the femur and tibia, higher
      levels of AFM above a certain level may impair cortical vBMD growth at weight
      bearing sites. Future studies in obese children will be needed to test this
      possibility.

PMID- 24113841
TI  - Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ
      induced diabetic rats.
AB  - Diabetes mellitus increases the risk of central nervous system (CNS) disorders
      such as stroke, seizures, dementia, and cognitive impairment. Berberine, a
      natural isoquinoline alkaloid, is reported to exhibit beneficial effect in
      various neurodegenerative and neuropsychiatric disorders. Moreover, astrocytes
      are proving critical for normal CNS function, and alterations in their activity
      and impaired oxidative stress could contribute to diabetes-related cognitive
      dysfunction. Metabolic and oxidative insults often cause rapid changes in glial
      cells. Key indicators of this response are increased synthesis of glial
      fibrillary acidic protein (GFAP) as an astrocytic marker. Therefore, we examined
      the effects of berberine on glial reactivity of hippocampus in streptozotocin
      (STZ)-induced diabetic rats, using GFAP immunohistochemistry. Lipid peroxidation,
      superoxide dismutase (SOD) activity, and nitrite levels were assessed as the
      parameters of oxidative stress. Eight weeks after diabetes induction, we observed
      increased numbers of GFAP(+) astrocytes immunostaining associated with increased
      lipid peroxidation, decreased superoxide dismutase activity, and elevated nitrite
      levels in the hippocampus of STZ-diabetic rats. In contrast, chronic treatment
      with berberine (50 and 100 mg/kg p.o. once daily) lowered hyperglycemia, reduced
      oxidative stress, and prevented the upregulation of GFAP in the brain of diabetic
      rats. In conclusion, the present study demonstrated that the treatment with
      berberine resulted in an obvious reduction of oxidative stress and GFAP
      immunoreactive astrocytes in the hippocampus of STZ-induced diabetic rats.

PMID- 24113842
TI  - TDP-43 regulates the microprocessor complex activity during in vitro neuronal
      differentiation.
AB  - TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA
      metabolism at several levels. Even if ubiquitously expressed, it is considered as
      a neuronal activity-responsive factor and a major signature for neurological
      pathologies, making the comprehension of its activity in the nervous system a
      very challenging issue. TDP-43 has also been described as an accessory component
      of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor
      complex, which is crucially involved in basal and tissue-specific RNA processing
      events. In the present study, we exploited in vitro neuronal differentiation
      systems to investigate the TDP-43 demand for the microprocessor function,
      focusing on both its canonical microRNA biosynthetic activity and its alternative
      role as a post-transcriptional regulator of gene expression. Our findings reveal
      a novel role for TDP-43 as an essential factor that controls the stability of
      Drosha protein during neuronal differentiation, thus globally affecting the
      production of microRNAs. We also demonstrate that TDP-43 is required for the
      Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating
      neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha
      target, resulted to be TDP-43-independent. These results implicate a previously
      uncovered contribution of TDP-43 in regulating the abundance and the substrate
      specificity of the microprocessor complex and provide new insights into TDP-43 as
      a key player in neuronal differentiation.

PMID- 24113844
TI  - The effect of ambient illumination on handheld display image quality.
AB  - Handheld devices such as smartphones and tablets are becoming useful in the
      medical field, as they allow physicians, radiologists, and researchers to analyze
      images with the benefit of mobile accessibility. However, for handheld devices to
      be effective, the display must be able to perform well in a wide range of ambient
      illumination conditions. We conducted visual experiments to quantify user
      performance for testing the image quality of two current-generation devices in
      different ambient illumination conditions while measuring ambient light levels
      with a real-time illuminance meter. We found and quantified that due to the high
      reflectivity of handheld devices, performance deteriorates as the user moves from
      dark areas into environments of greater ambient illumination. The quantitative
      analysis suggests that differences in display reflection coefficients do not
      affect the low illumination performance of the device but rather the performance
      at higher levels of illumination. 

PMID- 24113843
TI  - The role of secretory phospholipase A2 in the central nervous system and
      neurological diseases.
AB  - Secretory phospholipase A2 (sPLA2s) are small secreted proteins (14-18 kDa) and
      require submillimolar levels of Ca(2+) for liberating arachidonic acid from cell
      membrane lipids. In addition to the enzymatic function, sPLA2 can exert various
      biological responses by binding to specific receptors. Physiologically, sPLA2s
      play important roles on the neurotransmission in the central nervous system and
      the neuritogenesis in the peripheral nervous system. Pathologically, sPLA2s are
      involved in the neurodegenerative diseases (e.g., Alzheimer's disease) and
      cerebrovascular diseases (e.g., stoke). The common pathology (e.g., neuronal
      apoptosis) of Alzheimer's disease and stroke coexists in the mixed dementia,
      suggesting common pathogenic mechanisms of the two neurological diseases. Among
      mammalian sPLA2s, sPLA2-IB and sPLA2-IIA induce neuronal apoptosis in rat
      cortical neurons. The excess influx of calcium into neurons via L-type voltage
      dependent Ca(2+) channels mediates the two sPLA2-induced apoptosis. The elevated
      concentration of intracellular calcium activates PKC, MAPK and cytosolic PLA2.
      Moreover, it is linked with the production of reactive oxygen species and
      apoptosis through activation of the superoxide producing enzyme NADPH oxidase.
      NADPH oxidase is involved in the neurotoxicity of amyloid beta peptide, which
      impairs synaptic plasticity long before its deposition in the form of amyloid
      plaques of Alzheimer's disease. In turn, reactive oxygen species from NADPH
      oxidase can stimulate ERK1/2 phosphorylation and activation of cPLA2 and result
      in a release of arachidonic acid. sPLA2 is up-regulated in both Alzheimer's
      disease and cerebrovascular disease, suggesting the involvement of sPLA2 in the
      common pathogenic mechanisms of the two diseases. Thus, our review presents
      evidences for pathophysiological roles of sPLA2 in the central nervous system and
      neurological diseases.

PMID- 24113845
TI  - Mammographic artifacts on full-field digital mammography.
AB  - This study investigates the incidence of full-field digital mammographic (FFDM)
      artifacts with three systems at two institutions and compares the artifacts
      between two detector types and two grid types. A total of 4,440 direct and 4,142
      indirect FFDM images were reviewed by two radiologists, and artifacts were
      classified as patient related, hardware related, and software processing. The
      overall incidence of FFDM artifacts was 3.4% (292/8,582). Patient related
      artifacts (motion artifacts and skin line artifacts) were the most commonly
      detected types (1.7%). Underexposure among hardware related artifacts and high
      density artifacts among software processing artifacts also were common (0.7 and
      0.5%, respectively). These artifacts, specific to digital mammography, were more
      common with the direct detector type and the crossed air grid type than with the
      indirect type and linear grid type (p < 0.05). The most common mammographic
      artifacts on FFDM were patient related, which might be controlled by the
      instruction of a patient and technologist. Underexposure and high-density
      artifacts were more common with direct detector and crossed air type of grid.

PMID- 24113846
TI  - Musculoskeletal symptoms amongst clinical radiologists and the implications of
      reporting environment ergonomics--a multicentre questionnaire study.
AB  - This multicentre study aimed to assess compliance of the reporting environment
      with best ergonomic practice and to determine the prevalence of musculoskeletal
      symptoms related to working as a radiologist. All 148 radiology trainees and
      consultants in 10 hospitals across the region were invited to complete a
      musculoskeletal symptoms and reporting ergonomics questionnaire. Best ergonomic
      reporting practice was defined, following literature review, as being able to
      alter the following: monitor, desk, chair and armrest height, chair back support,
      ambient light, and temperature. The frequency that these facilities were
      available and how often they were used was determined. One hundred and twenty
      three out of 148 (83%) radiologists responded, and 38% reported radiology
      associated occupational injury. Lower back discomfort was the commonest radiology
      associated musculoskeletal symptom (41%). Only 13% of those with occupational
      injury sought the advice of occupational health. No reporting environments
      conformed completely to best ergonomic practice. Where certain facilities were
      available, less than a third of radiologists made personal ergonomic adjustments
      prior to starting a reporting session. Radiologists who had good self-assessed
      knowledge of best ergonomic practice had significantly less back discomfort than
      those with poor self-assessed knowledge (P < 0.005). We demonstrated high
      prevalence of musculoskeletal symptoms amongst radiologists. Poor compliance of
      the reporting environment with best ergonomic practice, in combination with our
      other findings of a low level of ergonomic awareness, low rates of making
      ergonomic adjustments and seeking appropriate help, may be implicated. We hope
      this study raises awareness of this issue and helps prevent long-term
      occupational injury amongst radiologists from poor ergonomic practice.

PMID- 24113848
TI  - A New Target for Glaucoma Therapy.

PMID- 24113847
TI  - Strategies for radiology reporting and communication part 3: patient
      communication and education.

PMID- 24113849
TI  - Tumor necrosis factor-alpha gene promoter -308 and -238 polymorphisms in patients
      with lung cancer as a second primary tumor.
AB  - BACKGROUND: Lung cancer is the most common second primary cancer. We investigated
      whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms were associated with
      the susceptibility and severity of lung cancer as the second primary cancer
      (LC2). MATERIAL/METHODS: This study included 104 patients from the group LC2. The
      control subjects included 2 groups. The first control group (LC1) comprised 201
      unrelated patients with lung cancer as a first primary cancer. The second control
      group (HC) comprised 230 healthy blood donors, matched for sex and age to the
      study group. RESULTS: The frequencies of the TNF-alpha-238 polymorphism GG
      genotype and the G allele were higher in the LC2 group than in the LC1 group, but
      the differences did not reach significance (p=0.054 and p=0.057, respectively).
      Similar differences were found in the TNF-alpha-238 polymorphism GG genotype and
      G allele between the LC2 group and the HC group (p=0.054 and p=0.057,
      respectively). In terms of the different types of lung cancer, patients with a
      second primary NSCLC (non-small cell lung cancer) more frequently had TNF-alpha
      238 polymorphism GG genotypes and G alleles than patients with a first primary
      NSCLC (the differences approached statistical significance: p=0.060, p=0.064,
      respectively). All (100%) patients of group LC2 (n=104) had the GG genotype and
      the G allele. GG genotype was exclusive and no A allele was found in group LC2.
      CONCLUSIONS: TNF-alpha-238 polymorphism GG genotype and the G allele could have a
      promotional effect on the development of NSCLC in the group of patients with LC2.

PMID- 24113850
TI  - Immediate and medium-term outcomes of cryoballoon-based pulmonary vein isolation
      in patients with paroxysmal and persistent atrial fibrillation: single-centre
      experience.
AB  - BACKGROUND: Pulmonary vein (PV) isolation with cryoballoon is a recently
      developed technique for the treatment of atrial fibrillation (AF) with acceptable
      mid-term results in terms of the success and safety. The purpose of our study is
      to identify the periprocedural complications, mid-term success rates and
      predictors of recurrence after AF ablation with cryoballoon. METHOD: A total of
      236 patients (54% male, mean age 54.6 +/- 10.45 years and 79.6% paroxysmal AF)
      with symptomatic AF underwent PV isolation with cryoballoon due to failure with
      >=1 antiarrhythmic drug previously. Procedural success, complications and follow
      up data were defined according to recent guidelines. RESULTS: Acute procedural
      success rate was 99.5%. Mean procedural and fluoroscopy times were 72.5 +/- 5.3
      and 14 +/- 3.5 min. At a median of 18 (6-27) months follow-up, 80.8% of
      paroxysmal AF patients and 50.0% of persistent AF patients were free from AF
      recurrence. In multivariate regression analysis, body mass index (BMI) (hazard
      ratio (HR), 1.35; 95% confidence interval (CI), 1.18-2.93, p = 0.001), smoking
      (HR, 2.12; 95% CI, 1.36-6.67, p < 0.001), non-paroxysmal AF (HR, 1.26; 95% CI,
      1.12-2.56, p = 0.024), duration of AF (HR, 1.42; 95% CI, 1.18-2.61, p = 0.015),
      left atrium (LA) diameter (HR, 2.42; 95% CI, 1.64-5.88, p < 0.001) and early AF
      recurrence (HR, 4.88; 95% CI, 2.86-35.6, p < 0.001) were independent predictors
      of AF recurrence following cryoablation. CONCLUSION: Our results showed that AF
      ablation with cryoballoon is effective and safe. Non-paroxysmal AF, duration of
      AF, smoking, BMI, LA diameter and early recurrence were found to be the most
      powerful predictors and could be helpful to select patients for appropriate
      therapeutic strategy.

PMID- 24113851
TI  - Comparison of left atrial electrophysiologic abnormalities during sinus rhythm in
      patients with different type of atrial fibrillation.
AB  - OBJECTIVE: The purpose of this study is to explore the left atrium (LA)
      electrophysiologic abnormalities in atrial fibrillation (AF) patients detected
      during sinus rhythm and to determine the relationship between the type of AF and
      the electrophysiologic substrate in the LA. METHODS: Eighty patients with AF (30
      paroxysmal AF, 22 persistent AF, and 28 long-standing AF) and 20 age- and sex
      matched patients with left-sided accessory pathway were prospectively studied.
      High-density three-dimensional electroanatomic mapping was performed during sinus
      rhythm in LA, which was divided into six segments for regional analysis. Mean
      bipolar voltage, low voltage zone (LVZ) distribution, LA activation time, and
      electrogram complexity were assessed. RESULTS: The LA mean voltage was 3.67 +/-
      0.68 mV in no AF group, 2.16 +/- 0.63 mV in the paroxysmal, 1.81 +/- 0.36 mV in
      the persistent, and 1.48 +/- 0.34 mV in the long-standing AF patients (P <
      0.001). The total LA activation time was 75.3 +/- 5.4 ms in no AF, 89.7 +/- 12.3
      ms in paroxysmal AF, 104.9 +/- 6.1 ms in persistent AF, and 115.6 +/- 12.1 ms in
      the long-standing AF patients, respectively (P < 0.001). With the progression of
      AF, there was a higher incidence of LVZ detection and increased prevalence of
      complex electrograms with 95 % of complex electrograms in areas with the bipolar
      voltage <= 1.3 mV in persistent and long-standing AF patients. CONCLUSION:
      Patients with AF have abnormal electrophysiologic substrate in sinus rhythm
      characterized by lower mean bipolar voltage, more prevalent complex electrograms,
      and longer LA activation time. This substrate progresses parallel to progression
      of AF type.

PMID- 24113852
TI  - Effect of defibrillation threshold testing-induced ventricular fibrillation on
      renal function.
AB  - INTRODUCTION: The effect of defibrillation threshold (DFT) testing with induction
      of ventricular fibrillation (VF) on renal function is currently unknown. This
      study examined the acute effect of DFT testing on renal function in patients
      undergoing implantable cardioverter defibrillator (ICD) implantation. METHODS AND
      RESULTS: We performed a prospective cohort study of 148 consecutive patients who
      underwent ICD implantation from January 1, 2007 to May 30, 2008. Patients were
      assigned to one of two cohorts: a DFT group who underwent DFT testing at device
      implantation and a no-DFT group that was not tested. Baseline and 24-h
      postprocedure renal function were assessed with measurements of serum creatinine
      and estimated glomerular filtration rate (GFR) by the Modified Diet in Renal
      Disease equation. Changes in serum creatinine and estimated GFR were compared
      between cohorts. Ninety-eight patients (66%) underwent DFT testing (average VF
      induction count, 1.5 +/- 0.9; mean VF duration, 10 +/- 4 s). Fifty patients (34%)
      were not tested. Patients in the no-DFT group had lower mean left ventricular
      ejection fraction, higher New York Heart Association class, higher atrial
      fibrillation incidence, and greater intravenous contrast utilization at device
      implant. Baseline and postprocedure serum creatinine values were similar between
      groups (baseline, 1.25 +/- 0.45 mg/dL; post-ICD, 1.26 +/- 0.5 mg/dL). Baseline
      GFR was lower in the DFT cohort (55.2 +/- 18.8 mL/min/BSA vs 63.7 +/- 22.7
      mL/min/BSA, p = 0.023). No significant differences between groups were observed
      in the mean change in serum creatinine or estimated GFR. CONCLUSIONS: DFT testing
      at the time of ICD implantation is not associated with acute adverse effects on
      renal function.

PMID- 24113853
TI  - [Prevention of bipolar disorders].
AB  - In the past, preventive measures for psychoses have focused mainly on
      schizophrenic disorders. Bipolar disorders are often diagnosed and treated with a
      significant delay. The expansion of preventive measures for bipolar disorders
      aims at minimizing the substantial negative consequences associated with the
      disease. Some of the shared aspects of prevention in psychoses and bipolar
      disorders are that the first symptoms commonly appear during adolescence and
      early adulthood and that there is a symptomatic overlap between the disorders. To
      improve efforts to seek early help, public information about mental illness, low
      threshold services as well as cooperation between adult, child and adolescent
      psychiatry are needed for this target group. One differences is that psychotic
      symptoms play a minor role in bipolar disorders. Specific biological markers,
      such as disturbances of sleep and circadian rhythm and clinical characteristics,
      such as substance use and behavioral problems in childhood and youth supplement
      (subsyndromal) clinical symptoms in a multifactorial risk model. Besides severity
      and frequency of symptoms, specific periodic course patterns are crucial.
      Strategies of early intervention require a careful consideration of risks and
      benefits. Two aims should be distinguished: the improvement of current
      symptomatology and the prevention of conversion to bipolar disorder. Currently,
      studies evaluating risks and benefits of such interventions are first conducted.
      Expertise and resources for early recognition of psychoses and bipolar disorders
      should be pooled. Common standards are the basis for advancement and
      implementation of preventive strategies for bipolar disorders. 

PMID- 24113854
TI  - [Long-acting injectable antipsychotics. Overview and advice for daily routine
      care].
AB  - Recent investigations have demonstrated a significant reduction of relapse and
      hospitalization rates associated with the use of long-acting injectable
      antipsychotics (LAIs) in the treatment of schizophrenia. There are only marginal
      differences in the effectiveness of different specific LAIs. Furthermore, LAIs
      are comparable to the oral equivalents with respect to effectiveness and side
      effects. The occurrence of extrapyramidal motor disorders (EPD) is less frequent
      in second generation (SG) LAIs than in first generation (FG) LAIs. Moreover,
      specific characteristics of some substances should be considered: In SG-LAIs
      immediate onset of action is only applicable for olanzapine and paliperidone and
      FG-LAIs should always be given as a test dose first to assure a general
      tolerance. All LAIs have a high variability of plasma levels which complicates
      the dose titration. Last but not least, current research concerning long-term
      consequences of continuous treatment with antipsychotics and the potentially
      poorer response to antipsychotics should be considered. 

PMID- 24113855
TI  - [Obituary for Christian Muller (1921-2013)].

PMID- 24113856
TI  - [Psychopathology in the social context].
AB  - In his treatise "Allgemeine Psychopathologie"(1913) (general psychopathology),
      Karl Jaspers contrasted the avoidance of methodical one-sidedness, which today is
      described as being interdisciplinary, and the danger of making partial
      conceptions absolute. He argued in favor of the combined observation of the
      psychopathological phenomena of the "natural human being" to be analyzed and
      explained by scientific (and epidemiological) methods along with understanding
      the individual case study of the "cultural human being", which a person is as
      well, by using humanitarian hermeneutic methods. Because he discussed the social
      context only briefly, we will illustrate this in the following with specific
      examples: 1. social influences on the contents and forms of the appearance of
      psychopathological phenomena together with definitions that separate these
      pathological from abnormal psychic phenomena, 2. social conditions, i.e.
      imprinting of dispositions as risk factors and the social situation of
      psychopathological phenomena and 3. their social consequences. Taken together
      these are arguments for a biopsychosocial model, which, however, to date is seen
      as arbitrary in respect to causal explanations, which remains vague and which
      present no rules for weighting the relevance of individual determinants. However,
      the educational and didactic value of the model, to consider systematically the
      patient in its entirety, is undisputed and should encourage psychiatrists to
      investigate in depth the complex constellations of conditions of psychic
      disturbances on the microlevel.

PMID- 24113857
TI  - The scientific basis for chelation: animal studies and lead chelation.
AB  - This presentation summarizes several of the rodent and non-human studies that we
      have conducted to help inform the efficacy and clinical utility of succimer (meso
      2,3-dimercaptosuccincinic acid) chelation treatment. We address the following
      questions: (1) What is the extent of body lead, and in particular brain lead
      reduction with chelation, and do reductions in blood lead accurately reflect
      reductions in brain lead? (2) Can succimer treatment alleviate the
      neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in
      the absence of lead poisoning, produce neurobehavioral deficits? Results from our
      studies in juvenile primates show that succimer treatment is effective at
      accelerating the elimination of lead from the body, but chelation was only
      marginally better than the complete cessation of lead exposure alone. Studies in
      lead-exposed adult primates treated with a single 19-day course of succimer
      showed that chelation did not measurably reduce brain lead levels compared to
      vehicle-treated controls. A follow-up study in rodents that underwent one or two
      21-day courses of succimer treatment showed that chelation significantly reduced
      brain lead levels, and that two courses of succimer were significantly more
      efficacious at reducing brain lead levels than one. In both the primate and
      rodent studies, reductions in blood lead levels were a relatively poor predictor
      of reductions in brain lead levels. Our studies in rodents demonstrated that it
      is possible for succimer chelation therapy to alleviate certain types of lead
      induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment
      protocol that produced a substantial reduction of brain lead levels could be
      identified for humans, a functional benefit might be derived. Finally, we also
      found that succimer treatment produced lasting adverse neurobehavioral effects
      when administered to non-lead-exposed rodents, highlighting the potential risks
      of administering succimer or other metal-chelating agents to children who do not
      have elevated tissue lead levels. It is of significant concern that this type of
      therapy has been advocated for treating autism. 

PMID- 24113859
TI  - Commentary on the abuse of metal chelation therapy in patients with autism
      spectrum disorders.
AB  - Approximately half a million patients with autism spectrum disorders are
      subjected to chelation therapy in the US annually. The overwhelming majority of
      such cases are chelated for non-accepted medical indications. These patients may
      seek evaluation when a urine sample is assayed after the administration of a
      chelating agent and the values obtained have been improperly compared to
      references ranges for non-chelated urines, causing falsely elevated results.
      Legitimate practitioners confronted with such data must decide, preferably in
      consultation with the patient or their guardian(s), whether to do further testing
      using legitimate methodology or to simply dismiss the results of the improper
      testing. Bayesian principles tell us that further testing is likely to yield
      results within normal reference ranges. However, under some circumstances, it is
      useful to do such testing in order to demonstrate that there is no need for
      chelation therapy. Unnecessary chelation therapy is expensive, can cause
      significant acute adverse effects, and may be associated with long-term
      consequences. 

PMID- 24113858
TI  - The role of chelation in the treatment of other metal poisonings.
AB  - These proceedings will review the role of chelation in five metals-aluminum,
      cadmium, chromium, cobalt, and uranium-in order to illustrate various chelation
      concepts. The process of "chelation" can often be oversimplified, leading to
      incorrect assumptions and risking patient harm. For chelation to be effective,
      two critical assumptions must be fulfilled: the presumed "metal toxicity" must
      correlate with a given body or a particular compartment burden, and reducing this
      compartmental or the body burden (through chelation) attenuates toxicity.
      Fulfilling these assumptions requires an established dose-response relationship,
      a validated, reproducible means of toxicity assessment (clinical, biochemical, or
      radiographical), and an appropriate assessment mechanisms of body or compartment
      burden. While a metal might "technically" be capable of chelation (and readily
      demonstrable in urine or feces), this is an insufficient endpoint. Clinical
      relevance must be affirmed. Deferoxamine is an accepted chelator for
      appropriately documented aluminum toxicity. There is a very minimal treatment
      window in order to address chelation in cadmium toxicity. In acute toxicity,
      while no definitive chelation benefit is described, succimer (DMSA),
      diethylenetriaminepentaacetate (DTPA), and potentially ethylenediaminetetraacetic
      acid (EDTA) have been considered. In chronic toxicity, chelation is unsupported.
      There is little evidence to suggest that currently available chromium chelators
      are efficacious. Similarly, scant human evidence exists with which to provide
      recommendation for cobalt chelation. DTPA has been recommended for cobalt
      radionuclide chelation, although DMSA, EDTA, and N-acetylcysteine have also been
      suggested. DTPA is unsupported for uranium chelation. Sodium bicarbonate is
      currently recommended, although animal evidence is conflicting. 

PMID- 24113860
TI  - Current use of chelation in American health care.
AB  - The National Center for Health Statistics estimates that more than 100,000
      Americans receive chelation each year, although far fewer than 1 % of these cases
      are managed by medical toxicologists. Unfortunately, fatalities have been
      reported after inappropriate chelation use. There are currently 11 FDA-approved
      chelators available by prescription although chelation products may also be
      obtained through compounding pharmacies and directly over the internet. Promotion
      of chelation training is prominent on some alternative and complementary medicine
      websites. 

PMID- 24113861
TI  - Recommendations for provoked challenge urine testing.
AB  - "Urine mobilization test," "challenge test," and "provoked urine test" are all
      terms used to describe the administration of a chelating agent to a person prior
      to collection of their urine to test for metals. There is no standard, validated
      challenge test. Despite recommendations by professional and government
      organizations against the use of provoked urine testing, the tests are still
      commonly used and recommended by some practitioners. Challenge testing utilizes a
      variety of chelating agents, including dimercaptosuccinic acid (DMSA),
      dimercaptopropanesulfonate (DMPS), and ethylenediaminetetraacetic acid (EDTA).
      The agents are given by a variety of routes of administration, doses used are
      inconsistent, and urine collection procedures vary. Additional problems with
      challenge tests include comparison of results to inappropriate reference ranges
      and creatinine correction of urine obtained within hours of chelator
      administration. Human volunteer studies demonstrate that mercury is detected in
      the urine of most people even in the absence of known exposure or chelator
      administration, and that urinary mercury excretion rises after administration of
      a chelator, regardless of exposure history and in an unpredictable fashion.
      Studies also demonstrate that challenge testing fails to reveal a "body burden"
      of mercury due to remote exposure. Chelating agents have been associated with
      adverse reactions. Current evidence does not support the use of DMPS, DMSA, or
      other chelation challenge tests for the diagnosis of metal toxicity. Since there
      are no established reference ranges for provoked urine samples in healthy
      subjects, no reliable evidence to support a diagnostic value for the tests, and
      potential harm, these tests should not be utilized. 

PMID- 24113862
TI  - Sweet's syndrome in a patient with metastatic melanoma after ipilimumab therapy.
AB  - Sweet's syndrome, a neutrophilic dermatosis, is a known paraneoplastic
      complication occurring with various malignancies. It has been infrequently
      reported in association with melanoma. Ipilimumab is an antibody against an
      inhibitory cytotoxic T-lymphocyte-associated antigen 4 receptor on T cells. It is
      associated with a range of immune-related toxicities. Sweet's syndrome in
      association with ipilimumab has been reported only briefly in the literature.
      However, neutrophilic infiltration has been seen in biopsies of patients with
      ipilimumab-associated enterocolitis. We report, in detail, the case of a woman
      with metastatic melanoma undergoing ipilimumab therapy. After the second cycle of
      immunotherapy, the patient presented with high-grade fever followed by a rash on
      her hands. No infectious etiology was elucidated after an extensive workup.
      Pathologic examination of the skin biopsy from the hands confirmed neutrophilic
      dermatosis. The patient was treated with systemic steroids achieving complete
      remission of the skin lesions. Physicians should be aware of Sweet's syndrome as
      a possible cutaneous side effect of ipilimumab therapy and be familiar with its
      management. 

PMID- 24113863
TI  - Combination of necroptosis and apoptosis inhibition enhances cardioprotection
      against myocardial ischemia-reperfusion injury.
AB  - PURPOSE: Necroptosis has been proposed as a mode of cell death that is a caspase
      independent programmed necrosis. We investigated whether necroptosis is involved
      in myocardial ischemia-reperfusion injury in isolated guinea pig hearts and, if
      so, whether simultaneous inhibition of necroptosis and apoptosis confers enhanced
      cardioprotection. METHODS: Isolated perfused guinea pig hearts were subjected to
      30 min ischemia and 4 h reperfusion (control = CTL, n = 8). Necrostatin-1
      (necroptosis inhibitor, 10 MUM), Z-VAD (apoptosis inhibitor, 0.1 MUM) and both
      inhibitors were administered starting 5 min before ischemia and during the
      initial 30 min of reperfusion (Nec, Z-VAD, Nec + Z-VAD; n = 8 each). Contractile
      recovery was monitored by left ventricular developed (LVDP) and end-diastolic
      (LVEDP) pressure. Infarct size was determined by triphenyltetrazolium chloride
      staining. Tissue samples were obtained after 4 h reperfusion to determine
      expression of receptor-interacting protein 1 (RIP1) and activated caspase 3 by
      Western blot analysis. RESULTS: After reperfusion, Nec + Z-VAD had higher LVDP
      and lower LVEDP compared with CTL. Infarct size was reduced in Nec and Z-VAD
      compared with CTL. Combination of necroptosis and apoptosis inhibition further
      reduced infarct size. Expression of activated caspase 3 was not increased in Z
      VAD and Nec + Z-VAD compared with Nec and CTL. Expression of RIP1 was preserved
      in Z-VAD and Nec + Z-VAD compared with CTL, suggesting RIP1-mediated necrosis is
      involved in myocardial ischemia-reperfusion injury. CONCLUSION: Necroptosis is
      involved in myocardial ischemia-reperfusion injury, and simultaneous inhibition
      of necroptosis and apoptosis enhances the cardioprotective effect. These findings
      may provide a novel, additive strategy for cardioprotection in acute myocardial
      infarction.

PMID- 24113865
TI  - Chemical to electrical transduction mechanisms from single metal oxide nanowire
      measurements: response time constant analysis.
AB  - Insight into chemical to electrical transduction mechanisms taking place at the
      surface of a single metal oxide nanowire is reported due to its outstanding
      importance for determining the characteristics of resistive solid state gas
      sensors. The surface chemical reaction kinetics is discussed considering
      competitiveness phenomena among different active sites and gas species on the
      nanowire taken as a metal oxide monocrystal at the nanoscale level. Experimental
      results for different representative gas molecules are shown to determine and
      understand sensor selectivity. The reported gas species are carbon monoxide and
      water vapour as general reference molecules, and ethanol and ammonia species as
      special references for gas-solid interactions, respectively, on acid and basic
      sites. Kinetic properties are proposed as particular signatures for each of the
      possible surface chemical reactions, allowing their identification and
      distinction. Likewise, features such as thermal inertia limitation and effects of
      the molecular and monoatomic absorbed oxygen are also estimated considering
      operation working modes based on nanowire self-heating. Furthermore, the
      applicability of a surface electrical field on a one-dimensional metal oxide
      nanostructure to enhance the surface ionization of the absorbed molecules is also
      reviewed as a new type of metal oxide based nanosensor for achieving improved
      selectivity.

PMID- 24113864
TI  - Subanalgesic ketamine enhances morphine-induced antinociceptive activity without
      cortical dysfunction in rats.
AB  - PURPOSE: Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has
      been used for the treatment of cancer pain as an analgesic adjuvant to opioids.
      However, ketamine is known to produce psychotomimetic side effects including
      cognitive impairments under a high-dose situation, presumably as the result of
      cortical dysfunction. Here, we investigated whether low-dose ketamine was useful
      as an analgesic adjuvant to morphine for pain control, focusing on frontocortical
      function. METHODS: To assess the analgesic effects of ketamine with or without
      morphine, we performed behavioral and histochemical experiments, using the hot
      plate test and c-Fos expression analysis in rats. The effect on cortical function
      was also determined by prepulse inhibition (PPI) of the acoustic startle and
      evoked potentials in the hippocampal CA1-medial prefrontal cortex (mPFC) synapses
      as measures of synaptic efficacy. RESULTS: Coadministration of ketamine as a
      subanalgesic dose significantly enhanced intraperitoneal morphine-induced
      antinociceptive response, which was measured as the increased reaction latency in
      the hot plate test. In addition, the noxious thermal stimulus-induced c-Fos
      expression in the ventrolateral periaqueductal gray matter was significantly
      suppressed by concomitant ketamine and morphine. In contrast, the subanalgesic
      dose of ketamine did not impair PPI and synaptic efficacy in the mPFC.
      CONCLUSION: The present results indicate that the morphine-induced analgesic
      effect is enhanced by a concomitant subanalgesic dose of ketamine without
      affecting cortical function. Our findings possibly support the clinical notion
      that low-dose ketamine as an analgesic adjuvant has therapeutic potential to
      reduce opioid dosage, thereby improving the quality of life in cancer pain
      patients.

PMID- 24113866
TI  - Want to neutralize HIV? Get help!

PMID- 24113867
TI  - Cancer immunotherapy for the elderly.

PMID- 24113869
TI  - Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A
      bioavailability and secreting VEGF-D.
AB  - Lymphangiogenesis is an important physiological response to inflammatory insult,
      acting to limit inflammation. Macrophages, dendritic cells, and lymphocytes are
      known to drive lymphangiogenesis. In this study, we show that neutrophils
      recruited to sites of inflammation can also coordinate lymphangiogenesis. In the
      absence of B cells, intranodal lymphangiogenesis induced during prolonged
      inflammation as a consequence of immunization is dependent on the accumulation of
      neutrophils. When neutrophils are depleted in wild-type mice developing skin
      inflammation in response to immunization or contact hypersensitization,
      lymphangiogenesis is decreased and local inflammation is increased. We
      demonstrate that neutrophils contribute to lymphangiogenesis primarily by
      modulating vascular endothelial growth factor (VEGF)-A bioavailability and
      bioactivity and, to a lesser extent, secreting VEGF-D. We further show that
      neutrophils increased VEGF-A bioavailability and bioactivity via the secretion of
      matrix metalloproteinases 9 and heparanase. Together, these findings uncover a
      novel function for neutrophils as organizers of lymphangiogenesis during
      inflammation. 

PMID- 24113870
TI  - Cbl ubiquitination of p85 is essential for Epo-induced EpoR endocytosis.
AB  - Erythropoietin (Epo) binding to the Epo receptor (EpoR) elicits downstream
      signaling that is essential for red blood cell production. One important negative
      regulatory mechanism to terminate Epo signaling is Epo-induced EpoR endocytosis
      and degradation. Defects in this mechanism play a key role in the overproduction
      of erythrocytes in primary familial and congenital polycythemia (PFCP). Here we
      have identified a novel mechanism mediating Epo-dependent EpoR internalization.
      Epo induces Cbl-dependent ubiquitination of the p85 regulatory subunit of PI3K,
      which binds to phosphotyrosines on EpoR. Ubiquitination allows p85 to interact
      with the endocytic protein epsin-1, thereby driving EpoR endocytosis. Knockdown
      of Cbl, expression of its dominant negative forms, or expression of an epsin-1
      mutant devoid of ubiquitin-interacting motifs all compromise Epo-induced EpoR
      internalization. Mutated EpoRs mimicking those from PFCP patients cannot bind
      p85, co-localize with epsin-1, or internalize on Epo stimulation and exhibit Epo
      hypersensitivity. Similarly, knockdown of Cbl also causes Epo hypersensitivity in
      primary erythroid progenitors. Restoring p85 binding to PFCP receptors rescues
      Epo-induced epsin-1 co-localization and EpoR internalization and normalizes Epo
      hypersensitivity. Our results uncover a novel Cbl/p85/epsin-1 pathway in EpoR
      endocytosis and show that defects in this pathway contribute to excessive Epo
      signaling and erythroid hyperproliferation in PFCP. 

PMID- 24113871
TI  - How I treat severe combined immunodeficiency.
AB  - Severe combined immunodeficiency (SCID) arises from different genetic defects
      associated with lymphocyte development and function and presents with severe
      infections. Allogeneic hematopoietic stem cell transplantation is an extremely
      effective way of restoring immunity in these individuals. Numerous multicenter
      studies have identified the factors determining successful outcome, and survival
      for SCID has shown great improvement. Advances in understanding the genetic basis
      of disease also mean that we increasingly tailor transplant protocols to the
      specific SCID form. Wherever possible, we attempt to transplant SCID patients
      without the use of cytoreductive conditioning, but it is clear that this is only
      successful for specific SCID forms and, although survival is good, in specific
      patients there are ongoing humoral defects. We aim to use matched related and
      unrelated donors (including cord blood) whenever possible and have limited the
      use of mismatched haploidentical donors. The development of autologous
      hematopoietic stem cell gene therapy provides another treatment of the X-linked
      and adenosine deaminase-deficient forms of SCID, and we discuss how we have
      integrated gene therapy into our treatment strategy. These developments together
      with the advent of universal newborn screening for SCID should allow for a highly
      favorable outcome for this otherwise lethal condition. 

PMID- 24113868
TI  - T-bet: a bridge between innate and adaptive immunity.
AB  - Originally described over a decade ago as a T cell transcription factor
      regulating T helper 1 cell lineage commitment, T-bet is now recognized as having
      an important role in many cells of the adaptive and innate immune system. T-bet
      has a fundamental role in coordinating type 1 immune responses by controlling a
      network of genetic programmes that regulate the development of certain immune
      cells and the effector functions of others. Many of these transcriptional
      networks are conserved across innate and adaptive immune cells and these shared
      mechanisms highlight the biological functions that are regulated by T-bet. 

PMID- 24113872
TI  - LRRK2 phosphorylates novel tau epitopes and promotes tauopathy.
AB  - Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most
      frequent cause of familial Parkinson's disease (PD). The neuropathology of LRRK2
      related PD is heterogeneous and can include aberrant tau phosphorylation or
      neurofibrillary tau pathology. Recently, LRRK2 has been shown to phosphorylate
      tau in vitro; however, the major epitopes phosphorylated by LRRK2 and the
      physiological or pathogenic consequences of these modifications in vivo are
      unknown. Using mass spectrometry, we identified multiple sites on recombinant tau
      that are phosphorylated by LRRK2 in vitro, including pT149 and pT153, which are
      phospho-epitopes that to date have been largely unexplored. Importantly, we
      demonstrate that expression of transgenic LRRK2 in a mouse model of tauopathy
      increased the aggregation of insoluble tau and its phosphorylation at T149, T153,
      T205, and S199/S202/T205 epitopes. These findings indicate that tau can be a
      LRRK2 substrate and that this interaction can enhance salient features of human
      disease.

PMID- 24113874
TI  - Brewers' spent grain (BSG) protein hydrolysates decrease hydrogen peroxide (H2O2)
      induced oxidative stress and concanavalin-A (con-A) stimulated IFN-gamma
      production in cell culture.
AB  - The present study investigated the bioactivity of protein hydrolysates and
      fractionated hydrolysates prepared from brewers' spent grain (BSG) using
      proteases, including Alcalase 2.4L, Flavourzyme and Corolase PP. Hydrolysates
      were designated K-Y, including fractionated hydrolysates with molecular weight
      (m.w.) < 3, <5 and >5 kDa. Where computable, IC50 values were lower in U937 (1.38
      9.78%) than Jurkat T cells (1.15-13.82%). Hydrolysates L, Q and R and
      fractionated hydrolysates of U and W (<3, <5, >5 kDa) significantly (P < 0.01)
      protected against hydrogen peroxide (H2O2)-induced reduction of superoxide
      dismutase (SOD) activity. A fractionated hydrolysate of W (<5 kDa) protected
      against H2O2-induced DNA damage, P < 0.01. Hydrolysates K, N, P, U, U > 5 kDa, V,
      V > 5 kDa, W, W > 5 kDa significantly (P < 0.05) reduced a concanavlin-A (con-A)
      stimulated production of interferon-gamma (IFN-gamma). In conclusion, BSG protein
      hydrolysates demonstrate bioactivity in vitro; lower m.w. hydrolysates (<3, <5
      kDa) show greatest antioxidant activity and unfractionated or higher m.w.
      hydrolysates (>5 kDa) possess anti-inflammatory effects. 

PMID- 24113873
TI  - Human neuroimaging as a "Big Data" science.
AB  - The maturation of in vivo neuroimaging has led to incredible quantities of
      digital information about the human brain. While much is made of the data deluge
      in science, neuroimaging represents the leading edge of this onslaught of "big
      data". A range of neuroimaging databasing approaches has streamlined the
      transmission, storage, and dissemination of data from such brain imaging studies.
      Yet few, if any, common solutions exist to support the science of neuroimaging.
      In this article, we discuss how modern neuroimaging research represents a
      multifactorial and broad ranging data challenge, involving the growing size of
      the data being acquired; sociological and logistical sharing issues;
      infrastructural challenges for multi-site, multi-datatype archiving; and the
      means by which to explore and mine these data. As neuroimaging advances further,
      e.g. aging, genetics, and age-related disease, new vision is needed to manage and
      process this information while marshalling of these resources into novel results.
      Thus, "big data" can become "big" brain science. 

PMID- 24113875
TI  - Lighting up cysteine and homocysteine in sequence based on the kinetic difference
      of the cyclization/addition reaction.
AB  - A novel one- and two-photon fluorescent probe CB1 has been developed for
      discriminating Cys and Hcy in a successive manner with high selectivity. The
      discrete time-dependent fluorescent responses enable us to sequentially detect
      Cys and Hcy in different time windows. Two-step reaction and kinetic modes were
      used to explain the sensing mechanism. As a promising biosensor for cell imaging,
      CB1 has been confirmed to exhibit membrane permeability to intact cells, low
      cytotoxicity to viable cells and photostability to ultraviolet light excitation.
      Furthermore, the results from the control assay have shown that the one- and two
      photon fluorescence of CB1 within cells is associated with intracellular mercapto
      biomolecules but yet there is little interference with physiological pH value,
      viscosity and common bioanalytes. Finally one- and two-photon fluorescent images
      of CB1 within living SiHa cells have been presented. 

PMID- 24113876
TI  - Double suicide gene therapy using human neural stem cells against glioblastoma:
      double safety measures.
AB  - With recent advancements in stem cell-based gene therapy, concerns about safety
      have grown. Stem cell-based gene therapies may pose the risk of immunological
      problems and oncogenesis. We investigated the feasibility of treating
      glioblastomas with neural stem cells [(NSCs), HB1.F3 cells] expressing double
      prodrug enzymes [cytosine deaminase (CD) and tyrosine kinase (TK)] to eliminate
      the NSCs following treatment for safety purposes. First, the in vitro and in vivo
      therapeutic efficacies of NSCs engineered with double prodrug enzymes (HB1.F3
      CD.TK cells) were compared to cells expressing a single prodrug enzyme (HB1.F3
      CD). Second, the degree of safety achieved by NSC elimination was compared with
      an in vitro viability assay of the NSCs after treatment with the double prodrugs.
      We further compared the differences in in vivo proliferation of control, single
      prodrug enzyme and double prodrug enzyme expressing NSCs. HB1.F3-CD.TK cells
      showed a better or comparable treatment outcome than HB1.F3-CD cells in vitro and
      in vivo. For safety, HB1.F3-CD.TK cells showed the least viability in vitro after
      treatment with prodrugs compared to HB1.F3 and HB1.F3-CD cells. Additionally, the
      in vivo proliferation among the injected NSCs found in the tumor was the smallest
      for HB1.F3-CD.TK cells. Double-prodrug enzyme-directed gene therapy shows good
      therapeutic efficacy as well as efficient eradication of the NSCs to ensure
      safety for clinical applications of stem cell-based gene therapies. 

PMID- 24113877
TI  - Measurements of the pons as a biomarker of progression for pediatric DIPG.
AB  - Treatment of pediatric diffuse intrinsic pontine glioma (DIPG) remains
      challenging, and reliable biomarkers of response are lacking. Radiographic
      response is a primary endpoint in many investigational studies of brain tumors,
      but there is no standard method of tumor measurement for DIPG, significant inter
      observer variability exists given the invasive nature of these tumors, and tumor
      measurements are not predictive of outcome. Because DIPGs involve a significant
      portion of the pons, we evaluated the reliability and prognostic value of one
      dimensional (1D) and two-dimensional (2D) pons measurements using anatomical
      landmarks rather than tumor boundaries. Patients with DIPG (n = 75) were
      evaluated longitudinally at our institution using MRI. Four readers independently
      performed 1D and 2D measurements of the pons using FLAIR images. Agreement and
      inter-reader variability were evaluated using differences among the six reader
      pairs and the coefficient of variation (CV). Prognostic value of pons
      measurements was calculated using Cox proportional hazards models, where relative
      hazard (RH) represents risk of death. Readers evaluated 384 exams. Agreement of
      readers' 1D and 2D measurements was strong (median difference between reader
      pairs 3.1 and 5.4%, respectively), with low inter-reader variability (median CV =
      3.1% and median CV = 4.8%, respectively). Increases in 1D and 2D pons
      measurements over time indicated poorer prognosis (RH = 2.29, p = 0.0025 and RH =
      1.13, p = 0.0016, respectively), with shorter overall survival. Pons measurements
      had low inter-reader variability compared to previously reported tumor
      measurement techniques and correlated with outcome in children with DIPG.
      Measurements of the pons (as opposed to direct measurements of tumor) are a
      viable in vivo biomarker for DIPG.

PMID- 24113878
TI  - Management of type 1 diabetes in children and adolescents.
AB  - Type 1 diabetes (T1D) is estimated to have a prevalence of approximately 1 in
      5000 among Indian children. Living with T1D is a challenge for the child and the
      family because of the significant burden of treatment in terms of regular
      injections and monitoring of blood sugar, and risk of acute and long term
      complications that this condition imposes. Optimal glycemic control in T1D
      requires a meticulous balance of insulin therapy with diet and exercise. With the
      earlier insulin regimens this required lot of discipline in the eating and
      activity pattern, which led to significant curtailment of the lifestyle. Now,
      with availability of better insulins, delivery and monitoring devices, greater
      flexibility in lifestyle has become possible. The ultimate breakthrough in terms
      of therapy of T1D shall be easy availability of accurate and affordable closed
      loop systems, and 'cure' through islet or stem cell transplant. A review of the
      ambulatory management of T1D in children and adolescents and the upcoming
      therapeutic advances is being presented in this paper. 

PMID- 24113879
TI  - First hour initiation of breastfeeding and exclusive breastfeeding at six weeks:
      prevalence and predictors in a tertiary care setting.
AB  - OBJECTIVE: To assess the prevalence of first hour breastfeeding initiation and
      exclusive breastfeeding at 6 wk and identify its barriers in healthy term babies
      born in a tertiary hospital setting. METHODS: A prospective observational cohort
      study was carried out in consecutively selected 400 mothers who delivered
      (normal, instrumental or cesarean) term healthy babies in a tertiary care
      hospital setting. All mother-infant dyads were enrolled within 48 h of delivery.
      RESULTS: Breastfeeding was initiated within first hour in 255 out of 400, i.e.,
      64 % of babies. Cesarean delivery and male gender were strongest risk factors for
      delayed initiation of breastfeeding [OR (95 % CI) = 1.99 (1.14-3.48) and 34.17
      (17.10-70.40) respectively]. Among the babies followed up till 6-8 wk, 83 % were
      exclusively breastfed. Breast milk substitutes were given in 172/400 (43 %)
      babies on day one, which emerged as an independent predictor of failure to
      continue exclusive breastfeeding at 6 wk (OR 2.96; 95 % CI 1.09-8.06). Odds of
      exclusive breastfeeding were two times higher in babies breastfed within first
      hour (n = 255/400, 64 %) when compared to babies initiated breastfeeds beyond
      first hour (n = 145/400, 36 %) (OR 2.01;05 % CI 1.12-3.61). CONCLUSIONS: Cesarean
      section and male gender emerged as significant risk factors for delayed
      initiation (beyond first hour) of breastfeeding in the index study cohort. In
      addition, use of breast milk substitute emerged as the only predictor for failure
      to continue exclusive breastfeeding at six weeks in a tertiary care hospital.

PMID- 24113880
TI  - ADad 2: the validation of the Screen for Child Anxiety Related Emotional
      Disorders for Anxiety Disorders among adolescents in a rural community population
      in India.
AB  - OBJECTIVE: Screen for Child Anxiety Related Emotional Disorders (SCARED), a
      measure found useful in different settings and cultures has not been validated in
      the subcontinent. This study validated this measure for identifying Anxiety
      Disorder (AD) among adolescents in an Indian community context. METHODS: Five
      hundred adolescents were assessed with SCARED and DSM-IV-TR reference standard
      for diagnosis of AD. The interviewers were experienced raters who were further
      trained to interview participants using Schedule for Affective Disorders and
      Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL).
      Sensitivity, specificity, likelihood ratios and predictive values for various
      SCARED cut-off scores were calculated. Test-retest reliability and inter-rater
      reliability of SCARED were examined. The dichotomized SCARED score was correlated
      with the DSM-IV-TR clinical diagnosis of AD to establish the criterion validity
      of SCARED as a measure of AD. RESULTS: A SCARED total score of >=21(Sn = 84.62%,
      Sp = 87.36%; AUC = 90%) is suggested for diagnostic use in Indian population.
      Specific threshold scores were identified for the Panic Disorder, Generalized
      Anxiety Disorder, Separation Anxiety Disorder and Social Anxiety Disorder
      subscales. The inter-rater reliability (ICC = 0.87) and test-retest reliability
      (ICC = 0.90) for SCARED is good. Besides the adequate face and content validity,
      SCARED demonstrates good internal consistency (Cronbach's alpha = 0.89) and item
      total correlation. There is a high concordance rate with the reference standard,
      DSM-IV-TR diagnosis [81%; Cohen's kappa = 0.42 (95% CI = 0.31 to 0.52); P =
      0.001] in classifying AD. CONCLUSIONS: SCARED has adequate psychometric
      properties and is now available for clinical and research work in India.

PMID- 24113881
TI  - Congenital Plasmodium vivax malaria and intracranial hemorrhage.

PMID- 24113882
TI  - Childhood Polyarteritis Nodosa: a prospective multicentre study from eastern
      India.
AB  - OBJECTIVE: To delineate the spectrum of clinical presentation and system
      involvement in childhood Polyarteritis Nodosa (PAN) in a multicentre follow up.
      METHODS: This prospective observational study included all children less than 12
      y attending pediatric rheumatological clinic of four different institutes in West
      Bengal or admitted with rheumatological symptoms and were diagnosed as childhood
      PAN by ACR and EULAR/PRES/PRINTO criteria. During the study period of 8 y, 15
      cases were categorized as childhood PAN with organ involvement. The children
      diagnosed as microscopic polyangiitis or cutaneous PAN were excluded. RESULTS:
      The mean age of presentation was 8.6 +/- 2.09 y with male to female ratio of 7:8.
      All had prolonged fever, severe myalgia, skin involvement and elevated acute
      phase reactants. Hypertension (93 %) and peripheral neuropathy (46 %) were
      notable findings. Nine had typical peripheral gangrene with ulceration, whereas
      rash of livedo reticularis was seen in 6 patients. None had renal, pulmonary or
      testicular involvement. Diagnosis was established in all patients by skin biopsy
      which showed necrotizing vasculitis of the medium sized vessels. The clinical
      presentations and diagnostic parameters were compared between the genders and no
      statistically significant difference was noted. All patients required
      corticosteroids while 10 patients needed additional immunosuppressives where
      there were uncontrolled symptoms of peripheral neuropathy or progressive gangrene
      despite treatment with corticosteroids. Cyclophosphamide was used most commonly
      (n = 7). Two required methyl prednisolone. Two children were lost to follow up.
      One patient had two relapses within three years. No mortality was observed.
      CONCLUSIONS: This multicentric study on childhood PAN, first of its kind from
      India, demonstrated a distinctive pattern of system involvement and clinical
      presentations.

PMID- 24113883
TI  - Revisiting extra hepatic portal vein obstruction in children from the north
      Indian gangetic plain.
AB  - OBJECTIVES: To study the demographic features, etiology, clinical, radiology and
      laboratory findings in children with Extra hepatic portal vein obstruction
      (EHPVO) from the North Indian Gangetic Plain. METHODS: A prospective analysis of
      53 patients of EHPVO (<14 y of age) was done. Data for clinical presentation,
      laboratory workup, endoscopic procedures, growth and development, management and
      outcome were analyzed. RESULTS: A total of 53 patients (32 male, 21 female) with
      mean age of 8.66 +/- 3.32 y at presentation were included. Growth retardation was
      present in 30 (56.60 %) patients at time of diagnosis. The most common presenting
      symptoms were upper gastrointestinal bleeding (86.80 %) and an incidental finding
      of splenomegaly (13.2 %). Hematological parameters of hypersplenism were present
      in 9 (17 %) patients. Protein C (PC), Protein S (PS), antithrombin III (AT)
      deficiency were found in 8 (20 %), 4 (10 %) and 6 (15 %) of the patients
      respectively in 40 patients tested. On first endoscopy, esophageal varices were
      present in all patients. Endoscopic sclerotherapy (EST)/band ligation (EBL) was
      performed in 46 bleeder patients and success rate was 83.3 % for sclerotherapy
      and 90 % for band ligation. CONCLUSIONS: The etiology of EHPVO in the majority of
      patients remains elusive. It results in impaired somatic growth. Sclerotherapy
      and endoscopic banding are effective means for treatment for bleeding varices. It
      is still not clear whether deficiency of anticoagulant proteins is a primary
      event or secondary to disease process.

PMID- 24113884
TI  - Severe pulmonary interstitial emphysema in a premature baby.

PMID- 24113885
TI  - Characteristics of incidentally discovered thyroid cancer.
AB  - IMPORTANCE: The incidence of thyroid cancer has been steadily increasing;
      however, no clear reason for the increase in incidence has been identified.
      OBJECTIVES: To compare incidentally discovered (ID) thyroid cancer via non
      thyroid-related imaging with nonincidentally discovered (NID) thyroid cancer, as
      well as determine if differences in tumor characteristics and patient
      presentation in ID thyroid cancer may help elucidate the increasing incidence of
      this disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record
      review at an academic tertiary care medical center of 31 patients with ID thyroid
      cancer and 207 patients with NID thyroid cancer evaluated at our institution
      during a 12-month period. MAIN OUTCOMES AND MEASURES: Patient demographics, tumor
      pathology, stage, tumor size, invasion, and metastasis were recorded. RESULTS:
      Mean age at diagnosis was 56.4 years for the ID group and 41.8 years for the NID
      group (P < .001). The ID group was 54.8% male compared with 13.5% in the NID
      group (P < .001). The ID group had higher stage disease compared with the NID
      group (P = .003). There was no difference in tumor size (P = .91), invasion (P =
      .76), lymph node involvement, or distant metastases (P > .99). CONCLUSIONS AND
      RELEVANCE: Patients with ID thyroid cancer tend to be older at presentation, have
      higher stage disease, and are more likely to be male compared with patients with
      NID thyroid cancer. There does not appear to be a significant difference in the
      size, pathology, or behavior of the tumor at presentation between ID and NID
      thyroid cancers. These findings imply that improved detection may not represent
      the only cause of the increased incidence of thyroid cancer.

PMID- 24113886
TI  - [New developments in X-PAP therapy for obstructive and central sleep-disordered
      breathing].

PMID- 24113887
TI  - [How Carl-Bertil Laurell and Sten Eriksson detected the alpha-1-antitrypsin
      deficiency 50 years ago and what then came--a somewhat headstrong and personal
      retrospection].

PMID- 24113888
TI  - Why we cannot grow a human arm.
AB  - There are several significant issues that prevent us from growing a human arm
      now, or within the next 10-20 years. From a tissue engineering perspective, while
      we can grow many of the components necessary for construction of a human arm, we
      can only grow them in relatively small volumes, and when scaled up to large
      volumes we lack the ability to develop adequate blood/nerve supply. From a
      genetic engineering perspective, we will probably never be able to turn on the
      specific genes necessary to "grow an arm" unless it is attached to a fetus and
      this presents enormous ethical issues related to farming of human organs and
      structures. Perhaps the most daunting problem facing the transplantation of a
      tissue engineered or transplanted arm is that of re-innervation of the structure.
      Since the sensory and motor nerve cells of the arm are located outside of the
      structure, re-innervation requires those nerves to regenerate over relatively
      large distances to repopulate the nervous system of the arm. This is something
      with which we have had little success. We can grow repair parts, but "growing an
      arm" presents too many insurmountable problems. The best we could possibly do
      with tissue engineering or genetic engineering would be the equivalent of a fetal
      arm and the technical problems, costs, and ethical hurdles are enormous. A more
      likely solution is a functional, permanent, neuroelectronically-controlled
      prosthesis. These are nearly a reality today. 

PMID- 24113889
TI  - Influence of nanostructures on the biological properties of Ti implants after
      anodic oxidation.
AB  - Anodic oxidation was applied to produce nanostructures on the surface of titanium
      (Ti) implants. The bioactivity of the Ti implants was evaluated by simulated body
      fluid soaking test. The biocompatibility was investigated by in vitro cell
      culture test. The results showed that bone-like apatite was formed on the
      anodized Ti surface, but not on the as-polished Ti surface after immersion in
      simulated body fluid for 2 weeks. Cells cultured on the anodized Ti surface
      showed enhanced cell adhesion and proliferation, compared to those cultured on
      the as-polished Ti surface. Based on these results, it can be concluded that
      anodic oxidation improved the bioactivity and biocompatibility of Ti surface,
      which was attributed to the formation of nanostructures as well as the
      nanostructure induced high surface roughness and hydrophilicity.

PMID- 24113890
TI  - Coating with artificial matrices from collagen and sulfated hyaluronan influences
      the osseointegration of dental implants.
AB  - Dental implants are an established therapy for oral rehabilitation. High success
      rates are achieved in healthy bone, however, these rates decrease in compromised
      host bone. Coating of dental implants with components of the extracellular matrix
      is a promising approach to enhance osseointegration in compromised peri-implant
      bone. Dental titanium implants were coated with an artificial extracellular
      matrix (aECM) consisting of collagen type I and either one of two
      regioselectively low sulfated hyaluronan (sHA) derivatives (coll/sHA1Delta6s and
      coll/sHA1) and compared to commercial pure titanium implants (control). After
      extraction of the premolar teeth, 36 implants were inserted into the maxilla of 6
      miniature pigs (6 implants per maxilla). The healing periods were 4 and 8 weeks,
      respectively. After animal sacrifice, the samples were evaluated
      histomorphologically and histomorphometrically. All surface states led to a
      sufficient implant osseointegration after 4 and 8 weeks. Inflammatory or foreign
      body reactions could not be observed. After 4 weeks of healing, implants coated
      with coll/sHA1Delta6s showed the highest bone implant contact (BIC;
      coll/sHA1Delta6s: 45.4%; coll/sHA1: 42.2%; control: 42.3%). After 8 weeks, a
      decrease of BIC could be observed for coll/sHA1Delta6s and controls
      (coll/sHA1Delta6s: 37.3%; control: 31.7 %). For implants coated with coll/sHA1,
      the bone implant contact increased (coll/sHA1: 50.8%). Statistically significant
      differences could not be observed. Within the limits of the current study, aECM
      coatings containing low sHA increase peri-implant bone formation around dental
      implants in maxillary bone compared to controls in the early healing period.

PMID- 24113891
TI  - Identification of a vitamin D3-specific hydroxylase genes through actinomycetes
      genome mining.
AB  - We previously completed whole-genome sequencing of a rare actinomycete named
      Sebekia benihana, and identified the complete S. benihana cytochrome P450
      complement (CYPome), including 21 cytochrome P450 hydroxylase (CYP), seven
      ferredoxin (FD), and four ferredoxin reductase (FDR) genes. Through targeted
      CYPome disruption, a total of 32 S. benihana CYPome mutants were obtained.
      Subsequently, a novel cyclosporine A region-specific hydroxylase was successfully
      determined to be encoded by a CYP-sb21 gene by screening the S. benihana CYPome
      mutants. Here, we report that S. benihana is also able to mediate vitamin D3
      (VD3) hydroxylation. Among the 32 S. benihana CYPome mutants tested, only a
      single S. benihana CYP mutant, DeltaCYP-sb3a, failed to show regio-specific
      hydroxylation of VD3 to 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3.
      Moreover, the VD3 hydroxylation activity in the DeltaCYP-sb3a mutant was restored
      by CYP-sb3a gene complementation. Since all S. benihana FD and FDR disruption
      mutants maintained VD3 hydroxylation activity, we conclude that CYP-sb3a, a
      member of the bacterial CYP107 family, is the only essential component of the in
      vivo regio-specific VD3 hydroxylation process in S. benihana. Expression of the
      CYP-sb3a gene exhibited VD3 hydroxylation in the VD3 non-hydroxylating
      Streptomyces coelicolor, implying that the regio-specific hydroxylation of VD3 is
      carried out by a specific P450 hydroxylase in S. benihana. 

PMID- 24113892
TI  - Overexpression of NADH-dependent fumarate reductase improves D-xylose
      fermentation in recombinant Saccharomyces cerevisiae.
AB  - Deviation from optimal levels and ratios of redox cofactors NAD(H) and NADP(H) is
      common when microbes are metabolically engineered. The resulting redox imbalance
      often reduces the rate of substrate utilization as well as biomass and product
      formation. An example is the metabolism of D-xylose by recombinant Saccharomyces
      cerevisiae strains expressing xylose reductase and xylitol dehydrogenase encoding
      genes from Scheffersomyces stipitis. This pathway requires both NADPH and NAD(+).
      The effect of overexpressing the glycosomal NADH-dependent fumarate reductase
      (FRD) of Trypanosoma brucei in D-xylose-utilizing S. cerevisiae alone and
      together with an endogenous, cytosol directed NADH-kinase (POS5Delta17) was
      studied as one possible solution to overcome this imbalance. Expression of FRD
      and FRD + POS5Delta17 resulted in 60 and 23 % increase in ethanol yield,
      respectively, on D-xylose under anaerobic conditions. At the same time, xylitol
      yield decreased in the FRD strain suggesting an improvement in redox balance. We
      show that fumarate reductase of T. brucei can provide an important source of
      NAD(+) in yeast under anaerobic conditions, and can be useful for metabolic
      engineering strategies where the redox cofactors need to be balanced. The effects
      of FRD and NADH-kinase on aerobic and anaerobic D-xylose and D-glucose metabolism
      are discussed. 

PMID- 24113894
TI  - Implementation of the sludge biotic index in a petrochemical WWTP in Brazil:
      improving operational control with traditional methods.
AB  - Microbiological analysis of activated sludge is an important tool for monitoring
      wastewater treatment plants (WWTP). The utilization of the sludge biotic index
      (SBI) provides helpful information in examining the quality of biological
      treatment process and has been tested for several different systems. Although its
      utilization has been increasing, it is still not widespread, especially in
      Brazil. Also, its applicability has been considered limited for some particular
      systems. Thus, it becomes important to evaluate the relations among operational
      and biological parameters of each WWTP in order to characterize the system and
      its variations. In this work, microscopic analysis were performed once a week for
      1 year (n = 54) and the results were compared to the physicochemical, operational
      parameters and efficiency of the plant along the period. The four seasons were
      comprised and analyzed, as we cannot neglect the influence of environmental
      changes in this subtropical region. Not only had we found a strong influence of
      the evaluated parameters on the structure of the biological community but there
      is also a good correspondence of SBI with the performance of the WWTP. More
      importantly, including microscopic analysis in the operational routine made it
      possible to notice even the slightest changes in the biological community that
      were not enough to diminish the SBI classification of the sludge, but were
      satisfactorily informative to show in advance to operators when to take
      corrective actions about an increase of COD and BOD in the influent and when it
      was necessary to discard the exceeding sludge. 

PMID- 24113893
TI  - Enhanced expression of genes involved in initial xylose metabolism and the
      oxidative pentose phosphate pathway in the improved xylose-utilizing
      Saccharomyces cerevisiae through evolutionary engineering.
AB  - Fermentation of xylose in lignocellulosic hydrolysates by Saccharomyces
      cerevisiae has been achieved through heterologous expression of the xylose
      reductase (XR)-xylitol dehydrogenase (XDH) pathway. However, the fermentation
      efficiency is far from the requirement for industrial application due to high
      yield of the byproduct xylitol, low ethanol yield, and low xylose consumption
      rate. Through evolutionary engineering, an improved xylose-utilizing strain
      SyBE005 was obtained with 78.3 % lower xylitol production and a 2.6-fold higher
      specific ethanol production rate than those of the parent strain SyBE004, which
      expressed an engineered NADP(+)-preferring XDH. The transcriptional differences
      between SyBE005 and SyBE004 were investigated by quantitative RT-PCR. Genes
      including XYL1, XYL2, and XKS1 in the initial xylose metabolic pathway showed the
      highest up-regulation in SyBE005. The increased expression of XYL1 and XYL2
      correlated with enhanced enzymatic activities of XR and XDH. In addition, the
      expression level of ZWF1 in the oxidative pentose phosphate pathway increased
      significantly in SyBE005, indicating an elevated demand for NADPH from XR. Genes
      involved in the TCA cycle (LAT1, CIT1, CIT2, KGD1, KGD, SDH2) and gluconeogenesis
      (ICL1, PYC1) were also up-regulated in SyBE005. Genomic analysis revealed that
      point mutations in transcriptional regulators CYC8 and PHD1 might be responsible
      for the altered expression. In addition, a mutation (Y89S) in ZWF1 was identified
      which might improve NADPH production in SyBE005. Our results suggest that
      increasing the expression of XYL1, XYL2, XKS1, and enhancing NADPH supply are
      promising strategies to improve xylose fermentation in recombinant S. cerevisiae.

PMID- 24113896
TI  - Massive left atrium thrombus.
AB  - The image shows a left atrium completely occupied by a giant non-homogeneous,
      irregularly-surfaced mass, obstructing the disc motion, mimicking severe mitral
      prosthetic stenosis. 

PMID- 24113897
TI  - Anterior mediastinal fat in Behcet's disease: qualitative and quantitative CT
      analysis.
AB  - The fat-rich anterior mediastinum could be a sensitive window for monitoring
      minute changes in vascularity induced by systemic vasculitis. To evaluate this
      hypothesis, an analysis of anterior mediastinal fat in patients with Behcet's
      disease and a control group was conducted. This study included 43 patients
      diagnosed with Behcet's disease within the last 11 years who underwent CT scan;
      55 patients were selected as a control population. Mediastinal fat was classified
      according to CT morphology. Comparison of serum inflammatory markers was
      performed for evaluation of disease activity according to morphologic types, and
      average Hounsfield unit of the anterior mediastinum was measured. Significantly
      higher mean CT attenuation was observed in the Behcet's disease group, compared
      with the control group (-48.5 +/- 33.5 vs. -67.7 +/- 18.7, respectively, P <
      0.05). Mediastinal fat types were classified as follows: pure fatty tissue (2 vs.
      31 % [Behcet's disease vs. control group]), diffuse soft tissue infiltration (16
      vs. 29 %), tubular structures (21 vs. 4 %), mixed infiltration with tubular
      structures (42 vs. 15 %), and evident thymic tissue (19 vs. 22 %). The value for
      mean mediastinal attenuation was significantly higher in the group with a high
      level of C-reactive protein than in the normal level group. The mean CT
      attenuation of anterior mediastinal fat is significantly higher in the Behcet's
      disease group, compared with the normal group. Although pathologic confirmation
      is needed, the cause is postulated to be either inflammatory neovascularization
      or minimal thymic hyperplasia induced by Behcet's disease.

PMID- 24113898
TI  - Application of decision-making theory to the regulation of muscular work rate
      during self-paced competitive endurance activity.
AB  - Successful participation in competitive endurance activities requires continual
      regulation of muscular work rate in order to maximise physiological performance
      capacities, meaning that individuals must make numerous decisions with regards to
      the muscular work rate selected at any point in time. Decisions relating to the
      setting of appropriate goals and the overall strategic approach to be utilised
      are made prior to the commencement of an event, whereas tactical decisions are
      made during the event itself. This review examines current theories of decision
      making in an attempt to explain the manner in which regulation of muscular work
      is achieved during athletic activity. We describe rational and heuristic
      theories, and relate these to current models of regulatory processes during self
      paced exercise in an attempt to explain observations made in both laboratory and
      competitive environments. Additionally, we use rational and heuristic theories in
      an attempt to explain the influence of the presence of direct competitors on the
      quality of the decisions made during these activities. We hypothesise that
      although both rational and heuristic models can plausibly explain many observed
      behaviours in competitive endurance activities, the complexity of the environment
      in which such activities occur would imply that effective rational decision
      making is unlikely. However, at present, many proposed models of the regulatory
      process share similarities with rational models. We suggest enhanced
      understanding of the decision-making process during self-paced activities is
      crucial in order to improve the ability to understand regulation of performance
      and performance outcomes during athletic activity. 

PMID- 24113899
TI  - Kayaking fatalities: could more appropriate helmets prevent fatal consequences?

PMID- 24113900
TI  - Reply: To PMID 23553415.

PMID- 24113901
TI  - Notes from the field: acute hepatitis and liver failure following the use of a
      dietary supplement intended for weight loss or muscle building--May-October 2013.
AB  - On September 9, 2013, the Hawaii Department of Health (HDOH) was notified of
      seven patients with severe acute hepatitis and fulminant liver failure of unknown
      etiology. Patients were previously healthy and sought medical care during May
      September 2013. Clinicians reported that the seven patients had all used OxyELITE
      Pro, a dietary supplement marketed for weight loss and muscle gain, before
      illness onset. 

PMID- 24113902
TI  - Effect of patient navigation on time to diagnostic resolution among patients with
      colorectal cancer-related abnormalities.
AB  - The objective of this study is to evaluate whether a patient navigation (PN)
      program is effective in reducing delay in diagnostic resolution among medically
      underserved patients with colorectal cancer (CRC)-related abnormalities in Tampa
      Bay, Florida. This study involved ten primary care clinics randomized either to
      receive navigation or to serve as controls (five clinics per arm). Each clinic
      identified all subjects with CRC-related abnormalities in the year prior to the
      clinic beginning participation in the Moffitt Patient Navigator Research Program.
      Patients with CRC-related abnormalities were navigated from the time of a
      colorectal abnormality to diagnostic resolution. Control patients received usual
      care, and outcome information was obtained from medical record abstraction. Using
      a frailty Cox proportional hazard model, we examined the length of time between
      colorectal abnormality and definitive diagnosis. One hundred ninety-three
      patients were eligible for the study because of a CRC-related abnormality (75
      navigated and 118 controls). Analysis of PN effect by two time periods of
      resolution (0-4 and >4 months) showed a lagged effect of PN. The adjusted time
      varying PN effect on diagnostic resolution compared to the controls was
      marginally significant (adjusted hazard ratio [aHR] = 1.15, 95% confidence
      interval = 1.02-1.29) after controlling for insurance status. The predicted aHR
      at 4 months was 1.2, but showed no significant effect until 12 months. For
      patients having an abnormal symptom of CRC, PN appeared to have a positive effect
      over time and sped diagnostic resolution after 4 months. However, the small
      sample size limits drawing a definitive conclusion regarding the positive PN
      effect.

PMID- 24113903
TI  - Influences of patient sociodemographics on cancer information received through
      the first 9 months of treatment.
AB  - This study evaluates the amount and change of information cancer patients report
      receiving related to disease, diagnostic tests, treatments, physical care, and
      psychosocial resources over 9 months of treatment. Information received by newly
      diagnosed, stages II-IV cancer patients receiving treatment (N = 139) at
      baseline, 4, and 9 months is examined through a two-stage latent growth model.
      Each information-received category was modeled with latent variables of intercept
      and slope. Random intercept and slope factors are then regressed on multiple
      sociodemographic covariates. The mean amount of information received does not
      change over time, but significant inter-individual variability was observed. Age
      (younger) and marital status (married) are significantly associated with a higher
      total amount of information received while education (less) and race (African
      American) are significantly associated with slower declines of information
      received over time. While the mean amount of information cancer patients receive
      is relatively constant over the course of treatment for the first 9 months, the
      level and rate of information received is somewhat varied based on patient
      characteristics. Healthcare professionals need to be aware of the varying amounts
      of information received by patients and ensure that the amount is consistent with
      the patient's individual needs.

PMID- 24113904
TI  - [Magnetic resonance imaging in patients with magnetic hearing implants: overview
      and procedural management].
AB  - BACKGROUND: Every year in Germany approximately 3,500 patients receive a cochlear
      implant or other hearing implants with an implantable magnet. At the same time
      more and more patients are examined by magnetic resonance imaging (MRI). For the
      indications and execution of this imaging modality a number of restrictions and
      safety measures have to be considered. METHODS: This article is based on the
      restrictions of the manufacturers and a selective literature search in PubMed
      using the following keywords: MRI compatibility/MRI safety + cochlea
      implant/auditory brainstem implant/Bonebridge/Carina/Esteem/Otomag/Sophono
      alpha/Vibrand Soundbridge. We included all 20 publications of this search
      concerning the MRI compatibility of the hearing implants complemented by papers
      cited in the primary articles. RESULTS: High electromagnetic field intensities as
      used in MRI can cause malfunction and dislocation of the implant or the magnet in
      the device. Older cochlear implants (CI) and the current CIs produced by Advanced
      bionics without explantation of the magnet, some CI models produced by the
      company Cochlear and the middle ear implants Carina(r)/Esteem(r) (older models)
      and Vibrant-Soundbridge(r) are not approved for MRI examinations. Other hearing
      prostheses are approved for 0.2 T, 1.0 T or 1.5 T MRI and in exceptional
      circumstances 3 T MRI. Recommendations of the manufacturers have to be followed,
      notably wearing a head bandage during the imaging procedure. The longitudinal
      axis of the patient's head has to be to positioned parallel to the main magnetic
      field of the scanner. The patient may not move the head laterally during the
      examination. Possible artefacts and the reduced validity of the results of skull
      MRI have to be considered when evaluating the indications for the examination.
      CONCLUSION: For patients wearing hearing implants with an implantable magnet the
      indications for MRI in devices with MRI certification should be rigorously
      restricted. Possible defects/dislocation of the implants may occur and the
      quality of the skull MRI images is reduced. A close contact between the
      radiologist and the implanting team is required. Other diagnostic procedure
      options should be exhausted before employing MRI.

PMID- 24113906
TI  - An OFF-ON chemosensor for biological and environmental applications: sensing Cd2+
      in water using catanionic vesicles and in living cells.
AB  - A new OFF-ON fluorescent chemosensor (L(1)) for Cd(2+) recognition based on a 5
      chloro-8-hydroxyquinoline pendant arm derivative of 1,4,7-triazacyclononane
      ([9]aneN3) will be presented and its photochemical features in an MeCN-H2O 1 : 1
      (v/v) mixture, in pure water, after inclusion within catanionic vesicles, and in
      living cells will be discussed. The coordination properties of L(1) both in
      solution and in the solid state were preliminarily studied and its selectivity
      towards Cd(2+)versus a set of different metal ions (Cu(2+), Zn(2+), Cd(2+),
      Pb(2+), Al(3+), Hg(2+), Co(2+), Ni(2+), Mn(2+), Mg(2+), K(+), Ca(2+), Ag(+), and
      Na(+)) was verified in MeCN-H2O 1 : 1 (v/v). In water, upon addition of
      increasing amounts of Cd(2+) to L(1) an enhancement of the fluorescence emission
      was detected. To overcome this serious drawback, L(1) was dissolved in an
      innovative catanionic vesicular solution based on sodium bis(2-ethylhexyl)
      sulfosuccinate, a traditional surfactant, and 1-dodecyl-3-methylimidazolium
      bromide, an ionic liquid. When enclosed within the vesicle bilayers in water,
      L(1) restored its fluorescence emission property upon addition of Cd(2+).
      Remarkably, L(1) enters the cellular membrane of living cells thus allowing the
      detection of intracellular Cd(2+). These findings encourage the application of
      this new fluorescent chemosensor in real samples for histological and
      environmental analyses. 

PMID- 24113905
TI  - Optical coherence tomography (OCT) of collagen in normal skin and skin fibrosis.
AB  - Optical coherence tomography (OCT) is a non-invasive imaging modality that is
      transforming clinical diagnosis in dermatology and other medical fields. OCT
      provides a cross-sectional evaluation of the epidermis and dermis and allows in
      vivo imaging of skin collagen. Upregulated collagen content is a key feature of
      fibrotic skin diseases. These diseases are often managed by the practitioner's
      subjective assessment of disease severity and response to therapies. The purpose
      of this review is to provide an overview of the principles of OCT and present
      available evidence on the ability of OCT to image skin collagen in vivo for the
      diagnosis and management of diseases characterized by skin fibrosis. We review
      OCT studies that characterize the collagen content in normal skin and fibrotic
      skin diseases including systemic sclerosis and hypertrophic scars secondary to
      burn, trauma, and other injury. We also highlight several limitations of OCT and
      suggest enhancements to improve OCT imaging of skin fibrosis. We conclude that
      OCT imaging has the potential to serve as an objective, non-invasive measure of
      collagen's status and disease progression for use in both research trials and
      clinical practice. The future use of OCT imaging as a quantitative imaging
      biomarker of fibrosis will help identify fibrosis and facilitate clinical
      examination in monitoring response to treatment longitudinally without relying on
      serial biopsies. The use of OCT technology for quantification of fibrosis is in
      the formative stages and we foresee tremendous growth potential, similar to the
      ultrasound development paradigm that evolved over the past 30 years.

PMID- 24113907
TI  - Arbuscular mycorrhizal symbiosis modulates antioxidant response in salt-stressed
      Trigonella foenum-graecum plants.
AB  - An experiment was conducted to evaluate the influence of Glomus intraradices
      colonization on the activity of antioxidant enzymes [superoxide dismutase (SOD),
      catalase (CAT), peroxidase (PX), ascorbate peroxidase (APX), and glutathione
      reductase (GR)] and the accumulation of nonenzymatic antioxidants (ascorbic acid,
      alpha-tocopherol, glutathione, and carotenoids) in roots and leaves of fenugreek
      plants subjected to varying degrees of salinity (0, 50, 100, and 200 mM NaCl) at
      two time intervals (1 and 14 days after saline treatment, DAT). The antioxidative
      capacity was correlated with oxidative damage in the same tissue. Under salt
      stress, lipid peroxidation and H2O2 concentration increased with increasing
      severity and duration of salt stress (DoS). However, the extent of oxidative
      damage in mycorrhizal plants was less compared to nonmycorrhizal plants. The
      study reveals that mycorrhiza-mediated attenuation of oxidative stress in
      fenugreek plants is due to enhanced activity of antioxidant enzymes and higher
      concentrations of antioxidant molecules. However, the significant effect of G.
      intraradices colonization on individual antioxidant molecules and enzymes varied
      with plant tissue, salinity level, and DoS. The significant effect of G.
      intraradices colonization on antioxidative enzymes was more evident at 1DAT in
      both leaves and roots, while the concentrations of antioxidant molecules were
      significantly influenced at 14DAT. It is proposed that AM symbiosis can improve
      antioxidative defense systems of plants through higher SOD activity in M plants,
      facilitating rapid dismutation of O2 (-) to H2O2, and subsequent prevention of
      H2O2 build-up by higher activities of CAT, APX, and PX. The potential of G.
      intraradices to ameliorate oxidative stress generated in fenugreek plants by
      salinity was more evident at higher intensities of salt stress. 

PMID- 24113908
TI  - Soft tissue angiofibroma: a case report.
AB  - Soft tissue angiofibroma is a recently described neoplasm that typically presents
      as a slowly growing, painless mass in the soft tissues of the lower extremities.
      Cytogenetic and molecular studies have identified a recurrent t(5;8)
      translocation. Treatment is simple excision. Existing data suggest that this
      tumor is benign and has a low rate of local recurrence. The radiologic and
      pathologic differential diagnoses for this lesion include both benign and
      malignant lesions, including plantar fibromatosis, tenosynovial giant cell tumor,
      fibroma of tendon sheath, epithelioid sarcoma, and low-grade myxofibrosarcoma.
      Proper identification of this benign lesion through radiologic and pathologic
      correlation is important to prevent misdiagnosis of a low-grade sarcoma. 

PMID- 24113909
TI  - Disposition of elderly patients after head and neck reconstruction.
AB  - IMPORTANCE: A patient's needs at discharge, particularly the need for nursing
      facility placement, may affect hospital length of stay and health care costs. The
      association between age and disposition after microvascular reconstruction of the
      head and neck has yet to be reported in the literature. OBJECTIVE: To determine
      whether elderly patients are more likely to be discharged to a nursing or other
      care facility as opposed to returning home after microvascular reconstruction of
      the head and neck. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2001,
      through December 31, 2010, patients undergoing microvascular reconstruction at an
      academic medical center were identified and their medical records systematically
      reviewed. During the study period, 457 patients were identified by Current
      Procedural Terminology codes for microvascular free tissue transfer for a head
      and neck defect regardless of cause. Seven patients were excluded for inadequate
      data on the postoperative disposition or American Society of Anesthesiologists
      (ASA) score. A total of 450 were included for analysis. MAIN OUTCOMES AND
      MEASURES: Demographic and surgical data were collected, including the patient
      age, ASA score, and postoperative length of stay. These variables were then
      compared between groups of patients discharged to different posthospitalization
      care facilities. RESULTS: The mean age of participants was 59.1 years. Most
      patients (n = 386 [85.8%]) were discharged home with or without home health
      services. The mean age of those discharged home was 57.5 years; discharge to home
      was the reference for comparison and odds ratio (OR) calculation. For those
      discharged to a skilled nursing facility, mean age was 67.1 years (OR, 1.055; P <
      .001). Mean age of those discharged to a long-term acute care facility was 71.5
      years (OR, 1.092; P = .002). Length of stay also affected the disposition to a
      skilled nursing facility (OR, 1.098), as did the ASA score (OR, 2.988).
      CONCLUSIONS AND RELEVANCE: Elderly patients are less likely to be discharged home
      after free flap reconstruction. Age, ASA score, and length of stay are
      independent factors for discharge to a nursing or other care facility.

PMID- 24113910
TI  - Lipoprotein subfraction profile and HDL-associated enzymes in sickle cell disease
      patients.
AB  - Although hypocholesterolemia is a reported finding in sickle cell disease (SCD),
      low-density lipoprotein (LDL)/high-density lipoprotein (HDL) subfractions and HDL
      associated enzymes have not been determined in SCD patients. Blood was collected
      from 38 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients who had not
      received blood transfusions in the last 3 months. Serum lipids were measured by
      automated analyzer while LDL and HDL subfraction analysis was done by continuous
      disc polyacrylamide gel electrophoresis. Serum levels of cholesteryl ester
      transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT),
      apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme
      linked immunosorbent assay (ELISA). Total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)
      levels were significantly decreased, while TG levels were significantly increased
      in SCD patients compared to controls. A significant decrease in intermediate
      density lipoprotein (IDL)-C, IDL-B, IDL-A and LDL-1 fractions were seen in SCD
      patients, while no significant difference was observed in small dense LDL
      particles. A significant decrease was seen in HDL-large, HDL-intermediate and HDL
      small fractions in SCD patients versus controls. Levels of LCAT and ApoA-1
      protein measured in SCD patients were significantly lower while no significant
      difference was observed in CETP and ApoB protein levels compared to controls. The
      reduction observed in LDL- and HDL-C in SCD patients was reflected as
      significantly decreased IDL, LDL-1 and HDL-subfractions. Decreased HDL
      subfractions may possibly lead to the reduced ApoA-1 and LCAT protein levels
      observed in SCD patients.

PMID- 24113911
TI  - Identification of plasmalogen cardiolipins from Pectinatus by liquid
      chromatography-high resolution electrospray ionization tandem mass spectrometry.
AB  - High resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS)
      was used to analyze cardiolipins (Ptd2Gro) including their plasmalogen forms from
      three species of the anaerobic beer-spoilage bacterial genus Pectinatus.
      Cardiolipins including their plasmalogens were analyzed by HR-ESI-MS/MS on
      Orbitrap and almost 100 cardiolipins (i.e. tetra-acyl--Ptd2Gro, plasmenyl-tri
      acyl--PlsPtd2Gro, and di-plasmenyl-di-acyl--Pls2Ptd2Gro) of three classes were
      identified. The structures of the molecular species that consist of various
      regioisomers and structurally similar compounds were revealed in detail. The high
      resolution mass spectrometry allowed the unambiguous structural assignment of
      Ptd2Gro, PlsPtd2Gro, and Pls2Ptd2Gro in the three species of Pectinatus, which
      contain predominantly odd numbered fatty acids.

PMID- 24113912
TI  - The interplay between partners' responsiveness and patients' need for emotional
      expression in couples coping with cancer.
AB  - The central aim of this longitudinal observational study was to test whether
      patients with a high need for emotional expression are especially sensitive to
      their partners' responsive behavior, and therefore at risk for depressive
      symptoms when responsiveness is withheld. Patients with colorectal cancer and
      their partners (n = 58) participated in a longitudinal study (3, 5 and 9 months
      after the diagnosis). Additionally to self-report measurements (i.e., patients'
      need for emotional expression, patients' depressive symptoms and patients'
      relationship satisfaction) couples were videotaped discussing cancer-related
      concerns. External observers coded partners' responsiveness (i.e., understanding,
      validation and caring) and patients' self-disclosures. Partner responsiveness
      predicted lower levels of depressive symptoms over time in patients who had a
      relatively high need for emotional expression above and beyond the effect of
      relationship satisfaction. We demonstrated that partners' understanding and
      validation are more important in explaining patients' depressive symptoms than
      partners' caring behavior. Our findings highlight the importance of the
      relational context in improving adaptation to cancer taking into account
      individual differences. 

PMID- 24113913
TI  - Chemistry of spices: bornyl 4-methoxybenzoate from Ferula ovina (Boiss.) Boiss.
      (Apiaceae) induces hyperalgesia in mice.
AB  - Ferula ovina (Boiss.) Boiss. is a traditional Iranian flavoring agent used as an
      ingredient of spices and condiments. METHODS AND RESULTS: GC-MS analyses of F.
      ovina aerial parts' essential oil revealed the presence of a number of rare
      aromatic esters of monoterpenic alcohols. The structures of these esters were
      corroborated by synthesis, and one of them, bornyl 4-methoxybenzoate, turned out
      to be a new natural compound. The antinociceptive activities of the oil and the
      new ester were assessed in mice using several different laboratory models. The
      oil exerted strong peripheral and moderate central analgesic activities.
      Surprisingly, mice treated with bornyl 4-methoxybenzoate had an increased
      sensitivity to the noxious stimulus compared to that of the control group. A
      dynamic hot plate test was used to demonstrate that bornyl 4-methoxybenzoate
      induces hyperalgesia and not allodynia. CONCLUSION: Essential oil constituents
      impart this spice with both antinociceptive and hyperalgesic potentially flavor
      related properties.

PMID- 24113914
TI  - A unique visual rhythm does not pop out.
AB  - We investigated attentional demands in visual rhythm perception of periodically
      moving stimuli using a visual search paradigm. A dynamic search display consisted
      of vertically "bouncing dots" with regular rhythms. The search target was defined
      by a unique visual rhythm (i.e., a shorter or longer period) among rhythmic
      distractors with identical periods. We found that search efficiency for a faster
      or a slower periodically moving target decreased as the number of distractors
      increased, although searching for a faster target was about one second faster
      than searching for a slower target. We conclude that perception of a visual
      rhythm defined by a unique period is not a "pop-out" process, but a serial one
      that demands considerable attention. 

PMID- 24113915
TI  - Understanding of action-related and abstract verbs in comparison: a behavioral
      and TMS study.
AB  - Does the comprehension of both action-related and abstract verbs rely on motor
      simulation? In a behavioral experiment, in which a semantic task was used,
      response times to hand-action-related verbs were briefer than those to abstract
      verbs and both decreased with repetition of presentation. In a transcranial
      magnetic stimulation (TMS) experiment, single-pulse stimulation was randomly
      delivered over hand motor area of the left primary motor cortex to measure
      cortical-spinal excitability at 300 or 500 ms after verb presentation. Two blocks
      of trials were run. In each block, the same verbs were randomly presented. In the
      first block, stimulation induced an increase in motor evoked potentials only when
      TMS was applied 300 ms after action-related verb presentation. In the second
      block, no modulation of motor cortex was found according to type of verb and
      stimulation-delay. These results confirm that motor simulation can be used to
      understand action rather than abstract verbs. Moreover, they suggest that with
      repetition, the semantic processing for action verbs does not require activation
      of primary motor cortex anymore. 

PMID- 24113916
TI  - Pattern randomness aftereffect.
AB  - Humans can easily discriminate a randomly spaced from a regularly spaced visual
      pattern. Here, we demonstrate that observers can adapt to pattern randomness.
      Following their adaption to prolonged exposure to two-dimensional patterns with
      varying levels of physical randomness, observers judged the randomness of the
      pattern. Perceived randomness decreased (increased) following adaptation to high
      (low) physical randomness (Experiment 1). Adaptation to 22.5 degrees -rotated
      adaptor stimuli did not cause a randomness aftereffect (Experiment 2), suggesting
      that positional variation is unlikely to be responsible for the pattern
      randomness perception. Moreover, the aftereffect was not selective to contrast
      polarity (Experiment 3) and was not affected by spatial jitter (Experiment 4).
      Last, the aftereffect was not affected by adaptor configuration (Experiment 5).
      Our data were consistent with a model assuming filter-rectify-filter processing
      for orientation inputs. Thus, we infer that neural processing for orientation
      grouping/segregation underlies the perception of pattern randomness. 

PMID- 24113917
TI  - The role of paediatricians in oral health of preschool children in the United
      Kingdom: a national survey of paediatric postgraduate specialty trainees.
AB  - AIM: There is little information available about oral health knowledge of
      paediatricians in the UK. The aim of this study was to assess the knowledge,
      training and attitudes of postgraduate (PG) paediatric trainees regarding oral
      health and determine the willingness to play an active role in promotion of
      better dental health in preschool children. METHODS: A web-based anonymous survey
      of PG paediatric trainees was sent to all 3,180 registered PG specialty trainees
      through their E-Portfolio by the Education and Training Support Team of the Royal
      College of Paediatrics and Child Health. RESULTS: A total of 479 PG speciality
      trainees at different levels of training completed the survey, resulting in a
      response rate of 15 %. Seven questions assessed the related training and
      attitudes of the PG specialty trainees towards their role in children's oral
      health. 96 % of respondents found the amount of training in oral health too
      little and 95 % responded they had not received any teaching during their
      training. Although 74 % of participants agreed that paediatricians should assess
      children's oral health, 61 % rated their ability as below average. The last three
      questions inquired about more specific oral health knowledge. Regarding
      recommended fluoride concentration in children's toothpastes in the UK, only 20 %
      of the PG specialty trainees responded correctly according to the current
      Department of Heath guidelines that it should be 1,000 ppm or more. CONCLUSIONS:
      Although the surveyed PG specialty trainees overwhelmingly believed they should
      play an active part in promoting better oral health for young children, a
      reported lack of training and up-to-date information appears to limit their role
      in education of parents and prevention of oral disease at an early stage.

PMID- 24113918
TI  - Effects of stress hormone cortisol on the mRNA expression of myogenenin, MyoD,
      Myf5, PAX3 and PAX7.
AB  - The present investigation was carried out to evaluate the effect of stress
      hormone cortisol on the myogenic markers in the C2C12 cells co-cultured with 3T3
      L1 preadipocytes. Co-culturing was achieved by transwell inserts with a 0.4 MUm
      porous membrane. C2C12 and 3T3-L1 cells were grown independently on the transwell
      plates. After differentiation, inserts containing 3T3-L1 cells were transferred
      to C2C12 plates for co-culturing. 10 MUg/MUl of cortisol was added to the medium.
      After 72 h of treatment, C2C12 cells which were in the lower well were harvested
      for analysis. RT-PCR analysis of myogenic markers such as of myogenin, MyoD,
      Myf5, PAX3 and PAX7 showed a significant reduction in the mRNA expression of
      these myogenic markers. In addition, cortisol increased calpain activity, which
      led to accelerated protein degradation, which in turn reduced the myogenic rate.
      In conclusion, cortisol treatment reduced mRNA expression of myogenic markers in
      the co-cultured C2C12 cells, which is quite distinct from one dimensional mono
      cultured C2C12 cells. 

PMID- 24113919
TI  - Primary culture of human face skin melanocytes for the study of
      hyperpigmentation.
AB  - Facial epidermal pigmentation and skin tumors can be caused by UV exposure and
      other physical and chemical irritations. In this report we describe the primary
      culture of melanocytes from human face skin. The ability to culture these
      melanocytes will enable their morphological and biological properties to be
      investigated. Skin specimens were obtained from patients who had undergone lower
      blepharoplasty procedures. Digestion with neutral protease and trypsin was used
      to obtain single cell suspensions of epidermal cells. The cells were cultured in
      M254 medium supplemented with human melanocyte growth solution. Cell morphology
      was observed using inverted microscopy. Melanocytes were positively identified
      using both L-DOPA staining and S-100 protein immunohistochemical staining.
      Immunofluorescence was used to confirm the expression of tyrosinase-related
      protein-1, a melanocyte-specific protein. The cellular ultrastructure of the
      melanocytes was observed by transmission electron microscopy. The cultured human
      melanocytes from face skin were multi-dendritic, and many mature melanosomes were
      observed. Therefore, using a specific culture medium, melanocytes from face skin
      can be successfully cultured and made available for further investigations. 

PMID- 24113920
TI  - The protective effects of Achyranthes bidentata root extract on the antimycin A
      induced damage of osteoblastic MC3T3-E1 cells.
AB  - Achyranthes bidentata (A. bidentata) Blume is a medicinal herb with the property
      of strengthening bones and muscles and ensuring proper downward flow of blood in
      terms of the therapeutic theory of traditional medicine. In the present study,
      the effect of A. bidentata root extract (AE) on osteoblast function was
      investigated in osteoblastic MC3T3-E1 cells. AE caused a significant elevation of
      alkaline phosphatase activity, collagen synthesis, osteocalcin production, and
      mineralization in the cells (P < 0.05). AE also decreased the production of TNF
      alpha, IL-6, and RANKL induced by antimycin A, mitochondrial electron transport
      inhibitor. Exposure of MC3T3-E1 cells to antimycin A caused significant reduction
      of cell viability and mineralization. However, pretreatment with AE prior to
      antimycin A exposure significantly reduced antimycin A-induced cell damage by
      preventing mitochondrial membrane potential dissipation, ATP loss, ROS release,
      and nitrotyrosine increase, suggesting that AE may be useful for protecting
      mitochondria against a burst of oxidative stress. Moreover, AE increased the
      phosphorylation of cAMP-response element-binding protein inhibited by antimycin
      A. Our study demonstrates that A. bidentata could significantly prevent
      osteoblast damage in aged patients. 

PMID- 24113921
TI  - Development of an Exergame for individual rehabilitation of patients with
      cardiovascular diseases.
AB  - An Exergame prototype for improved and patient-adapted rehabilitation was
      developed. A target heart rate for individual users was defined and tracked using
      a chest belt. Physical activity was tracked by two 3-axis accelerometers, fixed
      to both wrists. Dependent on the recorded heart rate and by means of a supporting
      factor and linear regression the movement of the user within the game was
      supported or hindered. The Exergame was evaluated on 15 healthy users regarding
      entertaining aspects, physical effort, and impressions concerning the handling of
      the whole setup. The support factor algorithm to reach the target heart rate was
      reliable in all subjects. 

PMID- 24113922
TI  - Analysis of postoperative bleeding and risk factors in transoral surgery of the
      oropharynx.
AB  - IMPORTANCE: With an increasing incidence of oropharyngeal carcinoma and
      prevalence of transoral surgical techniques, postoperative bleeding, with its
      associated risk factors, deserves evaluation. OBJECTIVE: To classify and review
      postoropharyngectomy hemorrhage rates and associated risk factors. DESIGN,
      SETTING, AND PARTICIPANTS: Single-institution, multicenter retrospective medical
      chart review analyzing surgical procedures in 906 patients treated with transoral
      surgery for oropharyngeal carcinoma at a tertiary care, academic referral center
      from 1994 to 2012. Tumor stage, previous treatment, resection method, and
      transcervical external carotid branch ligation were analyzed in relationship to
      postoperative hemorrhage rate, and severity. A novel classification system was
      created, grading bleeding episodes as minor, intermediate, major, or severe based
      on management method and related sequelae. RESULTS: Postoperative bleeding
      occurred in 5.4% of patients (49 of 906) with 67.3% of these (33 of 49) requiring
      operative intervention. Severe bleeding episodes were very rare (1.1% of
      patients). Transcervical external carotid system vessel ligation was performed
      with the primary resection in 15.6% of patients with no overall difference in
      bleeding rate or severity of bleeding in patients who underwent ligation vs those
      who did not (P = .21 and P = .66, respectively). Vessel ligation was performed
      more frequently in patients with a higher T stage (P = .002). In previously
      treated patients, severity of bleeding was decreased if vessels were ligated (P >
      .05). Higher T-stage tumors had a higher bleeding rate (P = .02). Bleeding rates
      were similar between those treated with laser (5.6%) and robotic (5.9%)
      oropharyngectomy (P = .80); however, patients with significantly higher T-stage
      tumors were treated with laser vs robot techniques (P < .001). CONCLUSIONS AND
      RELEVANCE: Transoral resection of oropharyngeal carcinoma is safe, and severe
      life-threatening hemorrhage is rare. Although transcervical vessel ligation did
      not result in an overall decrease in bleeding rate, there is a trend toward
      reduced postoropharyngectomy bleeding severity with ligation. We recommend
      ligation for higher T-stage tumors, primary tonsil tumors, and patients
      undergoing revision surgery.

PMID- 24113924
TI  - Salt and UV-B induced changes in Anabaena PCC 7120: physiological, proteomic and
      bioinformatic perspectives.
AB  - This study examines response of Anabaena sp. PCC 7120 to salt and UV-B stress by
      combining physiological, biochemical, proteomics and bioinformatics approaches.
      Sixty five significantly altered protein spots corresponding to 51 protein genes
      identified using MALDI-TOF MS/MS were divided into nine functional categories.
      Based on relative abundance, these proteins were grouped into four major sets. Of
      these, 27 and 5 proteins were up- and downregulated, respectively, both under
      salt and UV-B while 8 and 11 proteins showed accumulation in salt and UV-B
      applied singly. Some responses common to salt and UV-B included (i) enhanced
      expression of FeSOD, alr3090 and accumulation of MDA indicating oxidative stress,
      (ii) accumulation of PDH, G6P isomerase, FBPaldolase, TK, GAPDH and PGK
      suggesting enhanced glycolysis, (iii) upregulation of 6-PGD, 6PGL and NADPH
      levels signifying operation of pentose phosphate pathway, (iv) upregulation of
      Dps, NDK and alr3199 indicating DNA damage, and (v) accumulation of proteins of
      ribosome assembly, transcriptional and translational processing. In contrast,
      enhanced expression of RUBISCO, increased glycolate oxidase activity and ammonium
      content under salt signify the difference. Salt was found to be more damaging
      than UV-B probably due to a cumulative effect of ionic, osmotic and oxidative
      damage. A group of proteins having common expression represent decreased toxicity
      of salt and UV-B when applied in combination. 

PMID- 24113923
TI  - Govindjee at 80: more than 50 years of free energy for photosynthesis.
AB  - We provide here a glimpse of Govindjee and his pioneering contributions on the
      two light reactions and the two pigment systems, particularly on the water
      plastoquinone oxido-reductase, Photosystem II. His focus has been on excitation
      energy transfer; primary photochemistry, and the role of bicarbonate in electron
      and proton transfer. His major tools have been kinetics and spectroscopy
      (absorption and fluorescence), and he has provided an understanding of both
      thermoluminescence and delayed light emission in plants and algae. He pioneered
      the use of lifetime of fluorescence measurements to study the phenomenon of
      photoprotection in plants and algae. He, however, is both a generalist and a
      specialist all at the same time. He communicates very effectively his passion for
      photosynthesis to the novice as well as professionals. He has been a prolific
      author, outstanding lecturer and an editor par excellence. He is the founder not
      only of the Historical Corner of Photosynthesis Research, but of the highly
      valued Series Advances in Photosynthesis and Respiration Including Bioenergy and
      Related Processes. He reaches out to young people by distributing Z-scheme
      posters, presenting Awards of books, and through tri-annual articles on
      "Photosynthesis Web Resources". At home, at the University of Illinois at Urbana
      Champaign, he has established student Awards for Excellence in Biological
      Sciences. On behalf of all his former graduate students and associates, I wish
      him a Happy 80th birthday. I have included here several tributes to Govindjee by
      his well-wishers. These write-ups express the high regard the photosynthesis
      community holds for "Gov" and illuminate the different facets of his life and
      associations. 

PMID- 24113926
TI  - Synthesis of integerrimide A by an on-resin tandem Fmoc-deprotection
      macrocyclisation approach.
AB  - A solid-phase total synthesis of integerrimide A (1) is reported. This work
      employs a safety-catch linker which enables head-to-tail cyclisation of the
      required linear peptide 6 as a method of cleaving the peptide from the solid
      support, and highlights a new tandem approach to direct macrocyclisation. It
      provides access to useful quantities of 1 in 16 steps and 19% overall yield,
      based on the manufacturer's stated resin substitution from commercially available
      materials, and also verifies the absolute stereochemistry of the natural product.

PMID- 24113925
TI  - Regulation of cyclic electron flow in Chlamydomonas reinhardtii under fluctuating
      carbon availability.
AB  - The chloroplast must rapidly and precisely adjust photosynthetic ATP and NADPH
      output to meet changing metabolic demands imposed by fluctuating environmental
      conditions. Cyclic electron flow (CEF) around photosystem I is thought to
      contribute to this adjustment by providing ATP in excess of that supplied by
      linear electron low, balancing chloroplast energy budget when relative demand for
      ATP is high. We assessed the kinetics and energy production of CEF activation in
      Chlamydomonas reinhardtii under rapid changes of organic and inorganic carbon
      availability. Comparisons of transient electric field and chlorophyll
      fluorescence measurements indicated CEF was activated under conditions where ATP
      demand is expected to be high, consistent with a role in balancing the cellular
      ATP/NADPH budget under fluctuating environmental or metabolic conditions. CEF
      activation was not correlated with antenna state transitions, both in wild-type
      and the state transition mutant stt7-9, suggesting that CEF is rapidly regulated
      by allosteric or redox modulators. Comparing the CEF under ambient and high CO2
      conditions suggests an increase in required energy output of approximately
      1ATP/CO2 fixed, nearly sufficient to power proposed mechanistic models for the
      carbon-concentrating mechanism. Additionally, we see three-fold higher CEF rates
      in cells under steady-state conditions than cells under similar conditions with
      inhibited photosystem II, and up to five times higher in cells with severe
      depletion of inorganic carbon, implying that CEF has larger energetic capacity
      than predicted from some previous work. 

PMID- 24113927
TI  - Menthol cigarette use predicts treatment outcomes of weight-concerned smokers.
AB  - BACKGROUND: Studies have shown that individuals who smoke menthol cigarettes are
      less likely to quit smoking and more likely to relapse during a quit attempt. The
      current study investigated menthol cigarette use as a potential predictor of
      smoking cessation outcomes in a sample of treatment-seeking smokers. METHODS:
      This is a secondary analysis of data from a randomized controlled trial of low
      dose naltrexone augmentation of nicotine replacement designed to examine smoking
      cessation and postcessation weight gain in weight-concerned smokers. RESULTS:
      Analyses revealed that menthol use predicted lower quit rates. Among menthol
      smokers (N = 61), 13% were abstinent at week 26, and among nonmenthol smokers (N
      = 105), 30% were abstinent (Wald = 4.15, p = .04; odds ratio [OR] = 2.47; 95% CI
      = 1.04-5.90). Further, menthol smokers who quit smoking gained significantly more
      weight at week 26 (M = 14.87 lbs, SD = 9.08; t(37) = -2.22, p = .03) than
      nonmenthol smokers who quit (M = 7.95 lbs, SD = 7.53). CONCLUSIONS: Menthol
      cigarette use has not typically been evaluated as a predictor of smoking
      cessation outcomes, but emerging evidence suggests that consumption of menthol
      may make cessation more difficult. This study adds to the literature supporting
      the claim that smoking menthol cigarettes can have adverse effects on smoking
      cessation efforts and on other cessation-related outcomes, such as postcessation
      weight gain.

PMID- 24113928
TI  - Hostility as a predictor of affective changes during acute tobacco withdrawal.
AB  - INTRODUCTION: Hostility--a personality trait reflective of cynical attitudes and
      a general mistrust of others--is associated with smoking status and relapse risk.
      Yet, the mechanisms linking hostility and smoking are not entirely clear. In this
      lab study, we tested a socioaffective model that purports that high-hostility
      individuals smoke to cope with maladaptive social mood states (i.e., anger and
      low friendliness), which become expressed and exacerbated during acute tobacco
      withdrawal. METHODS: Following a baseline visit at which trait hostility was
      assessed, adult smokers (n = 153, >=10 cig/day) attended two counterbalanced lab
      visits: a deprived session following 16 hr of deprivation, and a nondeprived
      session. At both lab visits, affect and withdrawal symptoms were assessed at a
      single time point. RESULTS: Higher trait hostility predicted larger deprivation
      induced increases in several forms of negative affect (anxiety, depression,
      confusion; betas >= .20, ps <= .01) and a composite tobacco withdrawal symptom
      index (beta = .16, p = .04) but did not predict changes in positive emotions.
      These effects persisted after statistically controlling for gender, nicotine
      dependence, and depression. Other aspects of trait aggression (i.e., verbal
      aggression, physical aggression, anger) did not predict deprivation-induced
      changes in affect and withdrawal other than state anger. DISCUSSION: High
      hostility individuals appear to experience generalized exacerbations in several
      negative affective states during acute tobacco withdrawal. Increases in negative
      affect during tobacco withdrawal may motivate negative reinforcement-mediated
      smoking and could underlie tobacco addiction in high-hostility smokers.

PMID- 24113930
TI  - Do we really care about caries?

PMID- 24113929
TI  - Effects of smoking abstinence on cigarette craving, nicotine withdrawal, and
      nicotine reinforcement in smokers with and without schizophrenia.
AB  - INTRODUCTION: Schizophrenia is associated with a high prevalence of cigarette
      smoking. The aims of this study were to compare smokers with schizophrenia (SS)
      and control smokers without psychiatric illness (CS) on (a) cigarette craving and
      nicotine withdrawal symptom severity during a 72-hr smoking abstinence period;
      (b) nicotine reinforcement, before and after abstinence; and (c) latency to
      smoking lapse following abstinence. We also explored mediators of smoking lapse
      in SS and CS. METHODS: SS (n = 28) and CS (n = 27) underwent a nicotine versus
      denicotinized cigarette puff choice task before and after a 72-hr period of
      smoking abstinence that was experimentally controlled by providing cash
      reinforcement contingent on biochemical verification of abstinence. Twenty-four
      hours after the second choice task, participants could receive a low-value
      reinforcer if they had continued to abstain since the previous day. Those who
      remained abstinent were recontacted a week later to determine time of their
      smoking lapse. RESULTS: SS reported more severe cigarette craving and nicotine
      withdrawal symptoms throughout the 72-hr abstinence period, had greater nicotine
      preference after abstinence, and lapsed back to smoking significantly sooner than
      CS. The relationship between group and smoking lapse latency was mediated by
      baseline depression and nicotine withdrawal symptom severity but not by effects
      of abstinence on craving or nicotine reinforcement. CONCLUSIONS: Overall, these
      results indicate that negative affect is a key contributor to poor smoking
      cessation outcomes among those with schizophrenia.

PMID- 24113931
TI  - Verging on the dangerous.

PMID- 24113932
TI  - Congratulations.

PMID- 24113933
TI  - Crack link.

PMID- 24113934
TI  - Minocycline staining.

PMID- 24113935
TI  - Not ahead of the game.

PMID- 24113940
TI  - HIV-positive dentists.

PMID- 24113948
TI  - Improved access to care or lowered standard of care?
AB  - Health disparities abound in every profession, dentistry included. The most
      recent attempt to solve dental disparities that has been brought to light is the
      idea of training dental therapists in order to expand the dental workforce. While
      dental therapists have been around since the 1970s, only recently has the issue
      of allowing them to practice in the continental US been so forcefully raised and
      questioned. With the new healthcare act that will provide access to millions more
      starting in 2014, these disparities are getting much harder to ignore. We as
      healthcare professionals have a duty to strive to improve access to quality care
      and we will not know what quality of care is being provided until these
      therapists prove (or disprove) themselves. However, we must remember that all
      three populations - patients, therapists and dentists - must be heard, respected
      and protected as we navigate this new road to collaboration. 

PMID- 24113949
TI  - Oral surgery: part 3. Temporomandibular disorders.
AB  - Temporomandibular disorders (TMDs) are a collection of conditions affecting the
      temporomandibular joint (TMJ), the muscles of mastication and/or associated
      structures. They are probably one of the most commonly presenting chronic
      orofacial pain complaints to the dental profession. TMDs are recognised as a
      chronic illness and exert biopsychosocial effects on the patient and should
      therefore be managed in a biopsychosocial manner. This chapter will firstly cover
      the basic anatomy of the TMJ and its associated structures and then go on to
      discuss the signs and symptoms, aetiology, diagnosis, and broad management
      options for TMDs. 

PMID- 24113954
TI  - Summary of: the behaviour of preschool children receiving fluoride varnish
      application in a community setting.

PMID- 24113955
TI  - Summary of: permanent dentition caries through the first half of life.

PMID- 24113956
TI  - Can we learn, teach and practise dentistry anywhere, anytime?
AB  - Dentistry-related applications for mobile phones are becoming a popular way of
      accessing information for students, practitioners and patients. The aim of this
      article is to review the use of mobile technology, such as 'apps', within
      dentistry. Over time, there has been a change from desktop learning (D-learning)
      to mobile learning (M-learning) and this has only been possible with the aid of
      electronic media and the growth of the Internet. In spite of the increase in
      mobile applications, there is a need for any information to have a strong
      underlying evidence base. Several good examples of dental applications which take
      full advantage of this electronic medium are available. However, developers of
      mobile applications should provide good quality, peer-reviewed evidence to
      validate their material. 

PMID- 24113957
TI  - Guidance on the core content of an undergraduate curriculum in special care
      dentistry.
AB  - This paper has been previously published in the Journal of Disability and Oral
      Health and provides guidance on the core content of an undergraduate curriculum
      in special care dentistry by featuring three abstracts, published over the last
      year in the European Journal of Dental Education, on the context and
      methodological approach to the curriculum process. 

PMID- 24113958
TI  - The tooth -- a treasure chest of stem cells.
AB  - Mesenchymal stem cells can be obtained with ease from dental/oral tissue, making
      them an attractive source of autologous stem cells. They offer a biological
      solution for restoring damaged dental tissues such as vital pulp engineering,
      regeneration of periodontal ligament lost in periodontal disease, and for
      generation of complete or partial tooth structures to form biological implants.
      Dental mesenchymal stem cells share properties with mesenchymal stem cells from
      bone marrow and there is a considerable potential for these cells to be used in
      different stem-cell-based therapies, such as bone and muscle regeneration. In
      addition, their immunosuppressive-immunomodulatory properties make these cells a
      suitable source for treating immunodisorders like systematic lupus erythematosus.
      In addition, gingival tissue might also be a very good source of epithelial cells
      used in the treatment of severe ocular surface disorders. Being such an
      accessible source for different stem cells, the tooth and the attached gingival
      tissue (usually discarded in the clinics) represent an ideal source of autologous
      or allogeneic stem cells that can be used in the treatment of many clinical
      conditions in dentistry and medicine. 

PMID- 24113989
TI  - The behaviour of preschool children receiving fluoride varnish application in a
      community setting.
AB  - BACKGROUND: The behaviour of young children receiving mildly invasive dental
      preventive procedures in a community setting warrants more extensive research due
      to limitations in the literature.Objectives To document the behavioural profile
      of preschool children undergoing a preventive oral health intervention (fluoride
      varnish application) and to investigate this behaviour across children with
      different previous experience of the procedure, ages and initial anxiety states.
      METHOD: Nurse-child interactions were video recorded and child behaviours coded
      and analysed using a specially developed coding scheme (SABICS). Behaviour
      frequency was measured and presented diagrammatically, followed by independent
      sample non-parametric tests to distinguish behavioural group differences.
      RESULTS: Three hundred and three interactions were coded out of 456 recorded
      application sessions. 'Nonverbal agreement' behaviour was observed most
      frequently compared to disruptive behaviours. Younger preschool children tended
      to exhibit 'interact with instrument' behaviour more frequently than older
      children regardless of whether they had had previous application experience.
      Children who showed signs of initial anxiety were likely to display more
      disruptive behaviours during the later stage of the procedure compared with non
      anxious children. CONCLUSIONS: Dental staff working with preschool children are
      recommended to use encouragement-centred strategies to promote nonverbal
      cooperative behaviours in children. In addition, procedure instruments could be
      considered as a tool to gain child cooperation. Evidence of an autocorrelation
      effect of child behaviour was found, indicating that the early presentation of
      child behaviour predicted the behaviour of the child at later stages.

PMID- 24113990
TI  - Permanent dentition caries through the first half of life.
AB  - AIM: To describe the occurrence of dental caries at the person, tooth and tooth
      surface level from childhood to early mid-life. BACKGROUND: No studies have
      reported on age and caries experience in a population-based sample through the
      first half of life. METHODS: Prospective cohort study of a complete birth cohort
      (n = 1,037) born in 1972/73 in Dunedin, New Zealand. Dental examinations were
      conducted at ages 5, 9, 15, 18, 26, 32 and 38, and participation rates remained
      high. Surface-level caries data were collected at each age (WHO basic methods).
      Statistical analyses and graphing of data were undertaken using Intercooled Stata
      Version 10. RESULTS: Data are presented on dental caries experience in the
      permanent dentition at ages 9, 15, 18, 26, 32 and 38. Percentile curves are
      charted and reported for person-level caries experience. Data are also presented
      on the number of decayed teeth and tooth surfaces, (including root surfaces at
      age 38), as a function of the number of teeth and surfaces present, respectively.
      Across the cohort, the number of tooth surfaces affected by dental caries
      increased by approximately 0.8 surfaces per year (on average), while the
      percentage of at-risk tooth surfaces affected by caries increased by
      approximately 0.5% per year, with negligible variation in that rate throughout
      the observation period. CONCLUSION: These unique data show clearly that dental
      caries continues as a disease of adulthood, remaining important beyond childhood
      and adolescence and that rates of dental caries over time remain relatively
      constant.

PMID- 24113991
TI  - Safety and predictability of conscious sedation in dentistry -- a multi-centre
      regional audit: South and West Wales experience.
AB  - INTRODUCTION: There are no previously published reports of audits in conscious
      sedation from a group comprising the general dental services (GDS), community
      dental services (CDS) and hospital dental services (HDS). AIM: The main aim of
      this audit was to assess current practice within the group in relation to the
      safety and predictability of dental treatment undertaken with the aid of
      conscious sedation. METHODS: A total of nine centres collected data prospectively
      on 1,037 sedation episodes over the course of one year. Audit standards were
      locally agreed based on current evidence and local experience. They were set at a
      completion rate of 90% and an adverse incident rate of 2% or less. RESULTS: Based
      on the data collected, a completion rate of 92% and a minor adverse incident rate
      of 2.6% were recorded. CONCLUSIONS: The participating centres met the standards
      set locally for this audit. Current practice in the participating centres was
      found to be safe and predictable. The audit tool is being refined to improve the
      quality of data collection. Further research and service evaluation is
      recommended.

PMID- 24113992
TI  - The impact of the body mass index (BMI) on laparoscopic hysterectomy for benign
      disease.
AB  - PURPOSE: To investigate the influence of the body mass index (BMI) on
      laparoscopic hysterectomy, including all intra- and postoperative findings and
      complications. METHODS: We reviewed and analyzed the medical records of 200
      patients who underwent laparoscopic hysterectomy for benign disease at the
      Saarland University Hospital. The patient collective was subdivided into four
      weight groups on the basis of the current WHO BMI classification. Data analysis
      was carried out by a professional statistician. RESULTS: Over half of the women
      screened were overweight or obese. The operating times increased together with
      the BMI (p = 0.017). Blood losses differed significantly between the weight
      groups (p = 0.027), but ranged to a maximum of only 300 ml. One laparoconversion
      had to be performed. No other intraoperative complications occurred. During our
      follow-up time of 13.2 +/- 5.4 months, the overall rate of postoperative
      complications differed significantly between the weight groups (p = 0.008). The
      group of overweight women had the highest rate of complications and the group of
      obese women had the lowest. However, the rate of women who required readmission
      and reoperation was not elevated in the overweight group. CONCLUSION:
      Laparoscopic hysterectomy is a safe and feasible method even in obese and
      morbidly obese patients. Overweight and obesity increase the time needed to
      perform laparoscopic hysterectomy but do not seem to relevantly influence the
      rate of major intra- or postoperative complications.

PMID- 24113993
TI  - [Vena cava cement embolism after percutaneous kyphoplasty. Interventional
      radiological recovery in metastasized urothelial cancer].
AB  - For patients suffering from vertebral metastases vertebroplasty and kyphoplasty
      offer two relatively new treatment options for the stabilization of vertebral
      compression fractures. This can help to reduce the fracture-associated symptoms
      and can improve the quality of life. Cement extravasation is a specific
      complication of this therapy. This article reports a case of multiple cement
      paravasations in the paravertebral veins, the vena cava inferior and peripheral
      segmental and subsegmental pumonary arteries after kyphoplasty of an extensive
      pathological vertebral body fracture in a 64-year-old man suffering from
      metastatic urothelial cancer. 

PMID- 24113994
TI  - Colorectal carcinomas, KRAS p.G13D mutant allele-specific imbalance, and anti
      epidermal growth factor receptor therapy.

PMID- 24113995
TI  - Laryngeal release with slide tracheoplasty for long-segment congenital tracheal
      stenosis.
AB  - Slide tracheoplasty is a standard treatment for long-segment congenital tracheal
      stenosis (LCTS). However, in severe cases of LCTS, aggressive divisions of
      inferior constrictor muscle from the thyroid cartilage and extensive
      circumferential dissection of the upper tracheal segment are often necessary to
      mobilize the upper tracheal segment enough to make an anastomosis, but they
      increase the risks of anastomotic dehiscence, recurrent nerve injury, and
      impaired deglutition. Alternatively, laryngeal release provides safe mobilization
      of the upper tracheal segment, minimizing dissection of the inferior constrictor
      muscle and preserving the lateral tissue pedicle without circumferential
      dissection. We successfully performed laryngeal release with slide tracheoplasty
      on six patients with severe LCTS, and report our findings. 

PMID- 24113996
TI  - A successful patch angioplasty with auto-pulmonary wall for congenital coronary
      left main trunk occlusion in a young child.
AB  - Congenital occlusion of the left main coronary trunk is a life-threatening
      abnormality, and its optimal management remains controversial. This report
      describes a case of successful patch angioplasty with auto-pulmonary artery for a
      12-year-old boy with congenital left main trunk occlusion. We divided the main
      pulmonary artery, harvested a pulmonary artery wall strip, and performed patch
      angioplasty of the occluded left main trunk ostium. We were able to clearly
      expose the left main trunk behind the pulmonary artery because the obstruction
      was divided for the patch material. The postoperative course was uneventful, and
      coronary angiography at 4 months after surgery showed excellent patency of the
      left main trunk. The auto-pulmonary arterial wall was easy to handle during
      angioplasty, and its favorable durability has been established both in the Ross
      procedures and in an arterial switch procedure. Therefore, we conclude that patch
      angioplasty using a piece of the pulmonary arterial wall represents a good
      alternative to conventional coronary artery bypass grafting.

PMID- 24113997
TI  - Three-dimensional imaging of the inner limiting membrane folding on the
      vitreomacular interface in diabetic macular edema.
AB  - PURPOSE: To report the findings of fine folds on the retina obtained by spectral
      domain optical coherence tomography (OCT). METHODS: A retrospective non
      comparative case series; 26 eyes of diabetic macular edema (DME) patients who
      underwent vitrectomy were observed using three-dimensional (3D) images of OCT
      preoperatively and postoperatively. The specimens were investigated
      immunohistochemically. RESULTS: Using only tomography, non-tractional
      vitreoretinal interfaces were observed in 15 eyes and tractional vitreoretinal
      interfaces in the other 11 eyes. Using 3D imaging, we observed fine folds in 11
      eyes among 15 cases showing non-tractional interfaces. Based on these findings,
      the state of the vitreoretinal interface was classified into 3 patterns. Group 1,
      both tomography and 3D imaging showed smooth retinal surfaces. Group 2,
      tomography showed a smooth retinal surface, but 3D imaging showed fine folds on
      the retina. Group 3, both tomography and 3D imaging showed a tractional
      vitreoretinal interface with an obvious epiretinal membrane and/or taut posterior
      vitreous cortex. The fine folds in group 2 disappeared and macular edema improved
      after inner limiting membrane (ILM) peeling, and the CRT of groups 2 and 3
      reduced significantly. The fine folds were confirmed to involve the ILM because
      type IV collagen expression was detected in the surgically obtained specimens.
      CONCLUSION: We observed tangential fine folds of the ILM. These were detected by
      using only 3D imaging, and might be useful for investigating the optimal
      indication of vitrectomy for DME.

PMID- 24113998
TI  - AO spine classification system for thoracolumbar fractures.

PMID- 24113999
TI  - Co-expression of HLA-B7 and HLA-B27 alleles is associated with B7-restricted
      immunodominant responses following influenza infection.
AB  - It is recognized that host response following viral infection is characterized by
      immunodominance, but deciphering the different factors contributing to
      immunodominance has proved a challenge due to concurrent expression of multiple
      MHC class I alleles. To address this, we generated H2-K(-/-)/D(-/-) double
      knockout transgenic mice expressing either one or two human MHC-I alleles. We
      hypothesized that co-expression of different allele combinations figures
      critically in immunodominance and examined this in influenza-infected, double Tg
      MHC-I mice. In A2/B7 or A2/B27 mice, using ELISpot assays with the A2-restricted
      matrix I.58-66, the B7-restricted NP418-426 or the B27-restricted NP383-391
      influenza A (flu) epitopes, we observed the expected recognition of both peptides
      for both alleles. In contrast, in flu-infected B7/B27 mice, a significantly
      reduced level of B27/NP383-restricted CTL response was detected while there was
      no change in the B7/NP418-restricted CTL response. Flu-specific tetramer studies
      revealed a partial deletion of Vbeta8.1(+) NP383/B27-restricted CD8(+) T cells,
      and a diminished Vbeta12(+) CD8(+) T-cell expansion in B7/B27 Tg mice. Using HLA
      Tg chimeric mice, we confirmed these findings. These findings shed light on the
      immune consequences of co-dominant expression of MHC-I alleles for host immune
      response to pathogens. 

PMID- 24114000
TI  - Introductory paragraph - Volume 27, Issue 11.

PMID- 24114004
TI  - Sustained safety and efficacy of extended-shelf-life (90)Y glass microspheres:
      long-term follow-up in a 134-patient cohort.
AB  - PURPOSE: To validate our initial pilot study and confirm sustained safety and
      tumor response of extended-shelf-life (90)Y glass microspheres. We hypothesized
      that for the same planned tissue dose, the increase in number of glass
      microspheres (decayed to the second week of their allowable shelf-life)
      administered for the same absorbed dose would result in better tumor distribution
      of the microspheres without causing additional adverse events. METHODS: Between
      June 2007 and January 2010, 134 patients underwent radioembolization with
      extended-shelf-life (90)Y glass microspheres; data from 84 new patients were
      combined with data from our 50-patient pilot study cohort. Baseline and follow-up
      imaging and laboratory data were obtained 1 and 3 months after therapy and every
      3 months thereafter. Clinical and biochemical toxicities were prospectively
      captured and categorized according to the Common Terminology Criteria. Response
      in the index lesion was assessed using WHO and EASL guidelines. RESULTS: The mean
      delivered radiation dose was 123 Gy to the target liver tissue. The mean increase
      in number of microspheres with this approach compared to standard (90)Y glass
      microsphere dosimetry was 103%, corresponding to an increase from 3.84 to 7.78
      million microspheres. Clinical toxicities included fatigue (89 patients, 66%),
      abdominal pain (49 patients, 36.6%), and nausea/vomiting (25 patients, 18.7%).
      Grade 3/4 bilirubin toxicity was seen in three patients (2%). Two (1%) of the
      initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers
      were not seen in any of the subsequent 84 patients. According to WHO and EASL
      guidelines, response rates were 48% and 57%, respectively, and 21% demonstrated a
      complete EASL response. CONCLUSION: This study showed sustained safety and
      efficacy of extended-shelf-life (90)Y glass microspheres in a larger, 134-patient
      cohort. The increase in number of microspheres administered theoretically
      resulted in better tumor distribution of the microspheres without an increase in
      adverse events.

PMID- 24114005
TI  - Cost-effectiveness of (99m)Tc-MIBI in the evaluation of thyroid nodules for
      malignancy: a new lease of life for an old radiopharmaceutical?

PMID- 24114007
TI  - Stress and hemostasis: an update.
AB  - Numerous naturalistic, experimental, and mechanistic studies strongly support the
      notion that-as part of fight-or-flight response-hemostatic responses to acute
      psychosocial stress result in net hypercoagulability, which would protect a
      healthy organism from bleeding in case of injury. Sociodemographic factors,
      mental states, and comorbidities are important modulators of the acute
      prothrombotic stress response. In patients with atherosclerosis, exaggerated and
      prolonged stress-hypercoagulability might accelerate coronary thrombus growth
      following plaque rupture. Against a background risk from acquired prothrombotic
      conditions and inherited thrombophilia, acute stress also might trigger venous
      thromboembolic events. Chronic stressors such as job strain, dementia caregiving,
      and posttraumatic stress disorder as well as psychological distress from
      depressive and anxiety symptoms elicit a chronic low-grade hypercoagulable state
      that is no longer viewed as physiological but might impair vascular health.
      Through activation of the sympathetic nervous system, higher order cognitive
      processes and corticolimbic brain areas shape the acute prothrombotic stress
      response. Hypothalamic-pituitary-adrenal axis and autonomic dysfunction,
      including vagal withdrawal, are important regulators of hemostatic activity with
      longer lasting stress. Randomized placebo-controlled trials suggest that several
      cardiovascular drugs attenuate the acute prothrombotic stress response.
      Behavioral interventions and psychotropic medications might mitigate chronic low
      grade hypercoagulability in stressed individuals, but further studies are clearly
      needed. Restoring normal hemostatic function with biobehavioral interventions
      bears the potential to ultimately decrease the risk of thrombotic diseases. 

PMID- 24114008
TI  - Mental disorders and thrombotic risk.
AB  - Patients with psychosis, severe depression, or chronic stress are at increased
      risk for thromboembolism. Evidence suggests that tissue plasminogen activator
      (tPA) and plasminogen activator inhibitor-1 (PAI-1) imbalance may play an
      important role in pathophysiology of mental and thromboembolic disorders. tPA
      facilitates clot dissolution and participates in several brain functions,
      including response to stress, learning, and memory. Depression is characterized
      by high PAI-1 levels, and conditions related to a hypofibrinolytic status, such
      as polycystic ovary syndrome and metabolic syndrome, are associated with an
      increased risk for both depression and cardiovascular events.
      Depression/psychosis may occur when estrogen and progesterone levels decrease.
      Estrogen inhibits synthesis of transforming growth factor-beta (TGF-beta), a
      protein increasing PAI-1 synthesis, whereas progesterone induces brain-derived
      neurotrophic factor release, stimulating tPA expression in neurons. Synthetic
      progestogens (progestins) may cause severe depression. Notably, progestin
      metabolites, which may prevent synthesis of natural progesterone by feedback, do
      not cross the blood-brain barrier. Intense suprapubic menstrual cramp, which may
      relate to difficulty to dissolve clots, correlates with severe premenstrual
      tension. Exercise, which increases tPA synthesis, has antidepressive and
      antithrombotic effects. We suggest that thromboembolism and some mental disorders
      are mechanistically related: tPA-PAI-1 imbalance seems to be a common
      denominator. 

PMID- 24114009
TI  - Traumatic brain injury and its effect on coagulopathy.
AB  - Polytraumatic injury results in tissue factor (TF) release from damaged cells.
      The acute coagulopathy of trauma (ACT) occurs early and results from significant
      tissue injury and tissue hypoperfusion. ACT is augmented by therapies resulting
      in acidemia, hypothermia, and hemodilution contributing to trauma-induced
      coagulopathy. Coagulopathy associated with traumatic brain injury (TBI) results
      from the interplay of numerous variables. Because of the high concentration of TF
      in brain tissue, TBI has been believed to be associated with a greater degree of
      coagulopathy compared with injury in other body systems. TBI has also recently
      been shown to cause platelet dysfunction. Platelet receptor inhibition prevents
      cellular initiation and amplification of the clotting cascade, limiting thrombin
      incorporation, and stabilization of clot to stop hemorrhage. Therefore, head
      injury in the presence of polytrauma does appear to augment ACT and warrants
      close monitoring and appropriate intervention. 

PMID- 24114010
TI  - Intracerebral bleeding in patients on antithrombotic agents.
AB  - Patients treated with oral anticoagulants (OAC) carry a 7- to 10-fold higher risk
      of intracerebral hemorrhage (ICH) than patients without OAC. ICH related to oral
      anticoagulation (OAC-ICH) is a particularly severe form of stroke. The overall
      incidence of OAC-ICH ranges between 2 and 9 per 100,000 population/year and is
      expected to increase as the number of patients treated with OAC rises. Besides
      common risk factors of ICH such as age and hypertension, the intensity of
      anticoagulation, previous ischemic stroke, and the presence of cerebral
      vasculopathies (e.g., amyloid angiopathy, subcortical hypertensive arteriopathy)
      are associated with a greater risk of OAC-ICH. Mortality rates in OAC-ICH of 52
      to 67% considerably exceed those of ICH in nonanticoagulated patients. Factors
      that mediate worse outcome in OAC-ICH are more frequent and prolonged secondary
      hematoma enlargement and intraventricular hemorrhage, The current concept of
      emergency treatment in OAC-ICH is rapid restoration of effective coagulation
      using hemostatic factors such as prothrombin complex concentrate, fresh frozen
      plasma, factor IX concentrates, and recombinant factor VIIa in addition to
      vitamin K. Emergency management of ICH under treatment with the new direct OAC is
      a major challenge. In the absence of specific antidotes, prothrombin concentrates
      are recommended mainly on the basis of preclinical data. 

PMID- 24114011
TI  - BCL6 overexpression is associated with decreased p19 ARF expression and confers
      an independent prognosticator in gallbladder carcinoma.
AB  - B cell lymphoma 6 (BCL6) is a protein that is vital for lymphogenesis. Its
      expression has been well established in lymphoma, especially in diffuse large B
      cell lymphoma. Its role in carcinogenesis is less well understood. Previous study
      shows that BCL6 expression may regulate p19 functions, an important regulator for
      the p53 pathway. No prior study has attempted to evaluate the significance of
      BCL6 and p19(ARF) expression in a large cohort of patients with gallbladder
      carcinomas (GBCs). We selected 164 patients with GBC and performed immunostains
      for BCL6 and p19(ARF). BCL6 expression and p19(ARF) expression were evaluated
      using a histochemical score (H-score). We then correlated the results with
      various clinicopathological factors, disease-specific survival (DSS), and disease
      free survival (DFS). BCL6 overexpression was significantly associated with high
      pT status, high TNM stage, higher histological grade (p = 0.029), vascular
      invasion, perineurial invasion, high Ki-67 labeling index, and low p19
      expression. Importantly, BCL6 overexpression in GBC was strongly associated with
      worse DSS (p < 0.0001) and DFS (p < 0.0001) in the univariate analysis, and
      remained independently predictive of adverse outcomes (p = 0.001, hazard ratio
      (H.R.) = 3.098 for DSS; p = 0.002, H.R. = 2.255 for DFS). Low p19(ARF) expression
      was correlated with a poor DSS (p = 0.0144) and DFS (p = 0.0032) in the
      univariate analysis but was not prognosticatory in the multivariate analysis. In
      GBC, BCL6 overexpression correlated with adverse phenotypes and decreased
      p19(ARF) expression. BCL6 overexpression also independently predicts worse DSS
      and DFS, suggesting it has a role in tumorigenesis or carcinogenesis and could be
      a potential prognostic indicator in GBC.

PMID- 24114013
TI  - Association between the P53 codon 72 polymorphism and nasopharyngeal cancer risk.
AB  - The P53 codon 72 polymorphism has been identified as a critical biomarker in
      modifying the risk of nasopharyngeal cancer (NPC). Many studies have investigated
      the association between the polymorphism of P53 codon 72 and NPC risk; however,
      the findings across the published studies are inconsistent and inconclusive. To
      acquire a more precise assessment for this association, we conducted an updated
      meta-analysis. The PubMed, Embase, Web of Science, and Wanfang databases were
      searched for relevant case-control studies. Totally, seven independent
      publications with 1,133 cases and 1,678 controls were retrieved. The pooled odds
      ratio (OR) with corresponding 95% confidence interval (95% CI) was calculated.
      Increased risk of NPC was observed among individuals carrying the variant allele
      and genotypes of P53 codon 72 (OR Pro vs. Arg = 1.32, 95% CI 1.18-1.47, P OR <
      0.001; OR ProPro vs. ArgArg = 1.90, 95% CI 1.51-2.39, P OR < 0.001; OR ProArg +
      ProPro vs. ArgArg = 1.33, 95% CI 1.13-1.57, P OR = 0.001; OR ProPro vs. ArgArg +
      ProArg = 1.65, 95% CI 1.35-2.01, P OR < 0.001). Stratified analyses by ethnicity
      and source of controls also identified this significant relationship in Asians,
      Caucasians, and hospital-based case-control studies. There was no publication
      bias risk in our study. The updated meta-analysis supports the evidence that the
      polymorphism of P53 codon 72 is a risk factor for the development of NPC among
      the populations of both Asian and Caucasian.

PMID- 24114012
TI  - CD95 rs1800682 polymorphism and cervical cancer risk: evidence from a meta
      analysis.
AB  - CD95 is the first death receptor identified and characterized in recent years,
      and it plays important roles in the molecular network regulating cell death and
      survival. CD95 rs1800682 polymorphism is a common genetic polymorphism identified
      in the CD95 gene. Many publications evaluated the association between CD95
      rs1800682 polymorphism and cervical cancer risk, but the association remained
      inconclusive. To provide a more precise estimate on the association, a meta
      analysis was carried out. The association between CD95 rs1800682 polymorphism and
      cervical cancer risk was assessed by calculating the pooled odds ratio (OR) with
      its 95% confidence intervals (95% CI). On the basis of our inclusion criteria,
      ten studies with a total of 5,481 individuals were included into the meta
      analysis. There was obvious heterogeneity among the included studies. Meta
      analysis of the ten studies suggested that there was no association between CD95
      rs1800682 polymorphism and cervical cancer risk under all four genetic models
      (allele model: OR = 1.05, 95% CI 0.92-1.18, P = 0.478; homozygous model: OR =
      1.08, 95% CI 0.83-1.41, P = 0.550; dominant model: OR = 1.12, 95% CI 0.88-1.42, P
      = 0.347; recessive model: OR = 1.00, 95% CI 0.76-1.31, P = 0.978). Subgroup
      analysis by ethnicity suggested that there was no association between CD95
      rs1800682 polymorphism and cervical cancer risk in Asians, Caucasians, and
      Africans. Thus, the meta-analysis suggests that CD95 rs1800682 polymorphism is
      not associated with cervical cancer risk.

PMID- 24114014
TI  - Inhibition of Six1 promotes apoptosis, suppresses proliferation, and migration of
      osteosarcoma cells.
AB  - Sineoculis homeobox homolog 1 (Six1) is one of the transcription factors that act
      as master regulators of development and is frequently dysregulated in cancers.
      However, the biological role of Six1 is not clear in osteosarcoma. To address the
      expression of Six1 in osteosarcoma cells, three osteosarcoma cell lines (U2OS,
      SaOS-2, and MG63) and a human osteoblastic cell line (hFOB1.19) were used to
      detect the expression of Six1 by quantitative real-time polymerase chain reaction
      and western blotting. The results showed that Six1 was upregulated in
      osteosarcoma cell lines compared to human osteoblastic cell line hFOB1.19. To
      investigate the role of Six1 in osteosarcoma cells, 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay, flow cytometry analysis, and transwell
      chamber assays were used to determine the effects of Six1 on the cell viability,
      cycle, apoptosis, and migration properties in U2OS cells. The results showed that
      Six1 could promote U2OS cell proliferation and migration, and suppress U2OS cell
      apoptosis. In addition, we investigated the effects of Six1 on the expression of
      following proteins (cyclin D1, caspase-3, and vascular endothelial growth factor
      C (VEGF-C)). Results showed that Six1 could increase the expression of cyclin D1
      and VEGF-C, and decrease the expression of caspase-3. All these data suggested
      that Six1 might be involved in the promotion of growth, proliferation, and
      migration of U2OS cells, as well as the inhibition of apoptosis of U2OS cells.
      These data might provide information for the prediction of osteosarcoma prognosis
      and potential targets for therapy of osteosarcoma. 

PMID- 24114015
TI  - Mortality and recurrence patterns of breast cancer patients diagnosed under a
      screening programme versus comparable non-screened breast cancer patients from
      the same population: analytical survey from 2002 to 2012.
AB  - Breast cancer screening programmes seem to bring about significant benefits,
      including decreased mortality, although they may also have some drawbacks such as
      false-negative and false-positive results. This study aims to compare the
      clinical outcome of a group of patients undergoing a breast cancer screening
      programme with that of a synchronous non-screened group of patients matched for
      age and follow-up period. We studied basic characteristics of epidemiology,
      immunohistochemistry, loco-regional relapse, distant metastases, disease-free
      interval and overall and specific mortality. We compared 510 patients in the
      screened group with 394 non-screened patients, along the period of 2002-2012.
      Screening was applied on a target population of 49,847 and was based on double
      projection, double-read mammograms. Two years were allowed per round. Overall
      participation for the five rounds considered was 75.2%, with 86.5% coverage, and
      a total cumulative population of 123,445. The non-participant women amounted
      40,794. Tumour detection rate for the screened women was 3.8 per thousand
      (475/123,445), while the corresponding rate for non-participants was 9.4 per
      thousand (382/40,797). Incidence of luminal A subtype was 15% higher in screened
      than that in non-screened patients (95% confidence interval (CI) 8-22%).
      Conversely, the triple-negative subtype was 6% higher in the non-screened group
      (95% CI 2-10%). Incidence of breast conservative treatments and sentinel node
      biopsies was significantly higher in the screened group. Overall mortality was
      2.6 times higher in non-screened than that in screened group (95% CI 1.2-5.6)
      After 10 years of experience with our own screening programme, we believe that
      included patients receive a benefit versus comparable non-screened breast cancer
      patients, with acceptable benefit-risk relation.

PMID- 24114016
TI  - Prognostic role of D-dimer in patients with lung cancer: a meta-analysis.
AB  - D-dimer detection in patients suffering from a variety of different types of
      cancer has become a hot point as an emerging and promising biomarker. In this
      study, therefore, we evaluated the prognostic role of D-dimer in lung cancer.
      Initial literature was identified using the PubMed, EMBASE, and CNKI. The primary
      data was hazard ratio (HR) with 95% confidence interval (CI) of survival outcomes
      in candidate articles, including overall survival (OS) and disease-free survival
      (DFS). Finally, 11 eligible studies were included in this meta-analysis, which
      were published between 1996 and 2013. The estimated pooled HR and 95% CI for OS
      of all studies was 2.06 (95% CI 1.64-2.58, p < 0.00001) and the HR and 95% CI for
      DFS in one study was 3.38 (95% CI 1.17-9.75, p = 0.002). The HRs and 95% CIs for
      OS in Asian and non-Asian patients were 2.48 (95% CI 1.60-3.84, p < 0.0001) and
      1.89 (95% CI 1.44-2.47, p < 0.00001), respectively. When we further analyzed the
      data by various detecting methods, the pooled HR and 95% CI for OS were 3.22 (95%
      CI 1.99-5.21, p < 0.00001) for ELISA, 1.52 (95% CI 1.25-1.86, p < 0.0001) for
      Latex assay, and 1.79 (95% CI 1.19-2.69, p = 0.005) for immunoturbidimetry assay.
      We also did subgroup analysis according to the ratio of histological type and
      clinical stage. All the above analysis had positive results. This meta-analysis
      showed that D-dimer had a fine predictive role in lung cancer patients,
      especially in Asian group. Also, it demonstrated that D-dimer had a stronger
      predictive value by using the method ELISA.

PMID- 24114018
TI  - Squeeze on NHS has not yet resulted in worse care, report says.

PMID- 24114017
TI  - IL-12Rbeta1 deficiency and disseminated Mycobacterium tilburgii disease.
AB  - Mycobacterium tilburgii rarely causes disseminated disease. We describe a case of
      M. tilburgii infection in an otherwise healthy 33-year-old woman, who was found
      to carry bi-allelic mutations of the gene encoding the beta1 chain of the IL-12
      receptor. 

PMID- 24114019
TI  - Review of spectral imaging technology in biomedical engineering: achievements and
      challenges.
AB  - Spectral imaging is a technology that integrates conventional imaging and
      spectroscopy to get both spatial and spectral information from an object.
      Although this technology was originally developed for remote sensing, it has been
      extended to the biomedical engineering field as a powerful analytical tool for
      biological and biomedical research. This review introduces the basics of spectral
      imaging, imaging methods, current equipment, and recent advances in biomedical
      applications. The performance and analytical capabilities of spectral imaging
      systems for biological and biomedical imaging are discussed. In particular, the
      current achievements and limitations of this technology in biomedical engineering
      are presented. The benefits and development trends of biomedical spectral imaging
      are highlighted to provide the reader with an insight into the current
      technological advances and its potential for biomedical research.

PMID- 24114020
TI  - Innovative Troxler-free measurement of macular pigment and lens density with
      correction of the former for the aging lens.
AB  - Simplified measurement of macular pigment optical density (MPOD) is important
      because of the ocular health benefits that are attributed to these retinal
      carotenoids. Here, we describe a novel instrument designed for this purpose,
      based on heterochromatic flicker photometry (HFP), which removes a number of
      difficulties that subjects often experience with traditional HFP. The instrument
      generates 1.5- and 15-deg diameter, centrally viewed stimuli that alternate
      between blue and green colors generated by light emitting diodes (LED). The 15
      deg stimulus replaces the small, eccentrically viewed stimulus used in
      traditional HFP. Subjects adjust the blue LED intensity until flicker is
      eliminated in the case of the 1.5 deg stimulus and eliminated around the
      periphery in the case of the 15 deg stimulus. A microprocessor computes the
      subject's MPOD, in addition to the lens OD, and uses the latter to correct the
      MPOD. Good repeatability was confirmed through test-retest measurements on 52
      subjects. The overwhelming majority of them stated that they found the test easy.
      The importance of the lens correction on MPOD measurements was confirmed in a
      simulation study. The study showed that, without the correction, MPOD would show
      an apparent age-related decline in a population for whom there was no real age
      dependence.

PMID- 24114021
TI  - Confounding psychosis in the postpartum period.
AB  - This case report alerts the psychiatric clinician to consider nonpsychiatric
      etiologies of psychosis appearing during the postpartum period besides postpartum
      psychosis. The case includes a description of the patient's psychiatric
      presentation, admission to the inpatient psychiatric unit with subsequent
      transfer to the medicine department including neuroimaging and neurological
      consultation. The patient had a remission of psychosis after only two and half
      days of antipsychotic medication administration. Positive findings on the MRI
      suggested a demyelinating disease and a 4-month follow up MRI continued to be
      positive. The etiology was presumed to be a demyelinating disease. In conclusion,
      psychiatrists need to be alert to include nonpsychiatric pathologies in the
      differential diagnosis when a patient presents with psychosis in the postpartum
      period. 

PMID- 24114022
TI  - Combination of the serum carbohydrate antigen 19-9 and carcinoembryonic antigen
      is a simple and accurate predictor of mortality in pancreatic cancer patients.
AB  - PURPOSE: The aim of this study was to detect high-performance prognostic
      biomarkers of pancreatic cancer which would enable the identification of high
      risk patients. METHODS: The subjects were 324 patients who underwent radical
      surgery for pancreatic ductal adenocarcinoma without neoadjuvant therapy. We
      evaluated the prognostic impact of four perioperative serum tumor markers,
      including carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA).
      We also evaluated the indices by multiplying the values of two tumor markers
      (e.g., CA19-9 * CEA). RESULTS: The preoperative CA19-9 * CEA index had a strong
      correlation with the prognosis of patients with pancreatic cancer, even when the
      cut-off was set at the median value. CA19-9 * CEA >=500 was an independent
      predictor of mortality (hazard ratio: 1.642, p = 0.021). In the ROC curve
      analysis of early mortality after surgery, the CA19-9 * CEA index had the highest
      goodness of fit. The presence of CA19-9 * CEA >=500 had the largest attributable
      risk proportion because of its combined high predictive performance and
      prevalence. The postoperative CA19-9 * CEA index was also a significant
      predictive marker of mortality. CONCLUSION: The CA19-9 * CEA index is a strong
      prognostic biomarker that could help identify pancreatic cancer patients expected
      to have a poor prognosis so that they can be administered appropriate
      multidisciplinary treatment.

PMID- 24114036
TI  - Pelvic floor disorders: what's the best test?
AB  - Pelvic floor dysfunctions represent a common health problem affecting
      particularly post-menopausal women impacting significantly the quality of life. A
      large number of these patients suffer for many years without proper treatment
      often due to the lack of objective findings necessary to plan proper treatment.
      Because abnormalities of the different pelvic compartments are frequently
      associated, thorough diagnostic characterization of how many compartments are
      affected is paramount in order to plan the management approach that can include a
      multidisciplinary surgical approach. This pictorial essay will review the
      different imaging methods used for the characterization of these disorders, how
      to do them and its rationale providing a clinically understandable interpretation
      with clinical correlates and a correlation between fluoroscopic and MR
      defecography in order to illustrate the strengths and shortcomings of each. The
      need to use a standardized, reliable, and clinically understandable method of
      quantification has become more obvious in the last decades with the increasing
      rate of scientific and professional interchanges. A review of the grading systems
      used to convey the imaging findings also highlights the importance of using a
      standardized tool for comparing and communicating clinical findings
      understandable to referring physicians with proven inter-observer and intra
      observer agreement of the examinations. 

PMID- 24114037
TI  - The symptom burden of cancer: Evidence for a core set of cancer-related and
      treatment-related symptoms from the Eastern Cooperative Oncology Group Symptom
      Outcomes and Practice Patterns study.
AB  - BACKGROUND: A set of common cancer-related and treatment-related symptoms has
      been proposed for quality of care assessment and clinical research. Using data
      from a large, multicenter, prospective study, the authors assessed the effects of
      disease site and stage on the percentages of patients rating these proposed
      symptoms as moderate to severe. METHODS: The severity of 13 symptoms proposed to
      represent "core" oncology symptoms was rated by 3106 ambulatory patients with
      cancer of the breast, prostate, colon/rectum, or lung, regardless of disease
      stage or phase of care; 2801 patients (90%) repeated the assessment 4 to 5 weeks
      later. RESULTS: At the time of the initial assessment, approximately 33% of the
      patients reported >= 3 symptoms in the moderate-to-severe range; 11 of the 13
      symptoms were rated as moderate to severe by at least 10% of all patients and 6
      were rated as moderate to severe by at least 20% of those receiving active
      treatment. Fatigue/tiredness was the most severe symptom, followed by disturbed
      sleep, pain, dry mouth, and numbness/tingling. More patients with lung cancer and
      patients receiving active treatment reported moderate to severe symptoms.
      Percentages of symptomatic patients increased by disease stage, less adequate
      response to therapy, and declining Eastern Cooperative Oncology Group performance
      status. The percentages of patients reporting moderate to severe symptoms were
      stable across both assessments. CONCLUSIONS: The results of the current study
      support a core set of moderate to severe symptoms that are common across
      outpatients with solid tumors, that can guide consideration of progression-free
      survival as a trial outcome, and that should be considered in clinical care and
      in assessments of quality of care and treatment benefit.

PMID- 24114038
TI  - Chemically triggered C-ON bond homolysis in alkoxyamines: regioselectivity and
      chemoselectivity.
AB  - Recently, we examplified the activation of the C-ON bond homolysis by
      protonation, alkylation, benzylation, acylation, oxidation and complexation with
      a Lewis acid of the nitrogen atom of the 1-(pyridin-4-yl)ethyl fragment (Chem.
      Commun., 2011, 4291 and Org. Lett., 2012, 358) and of the 1-(pyridin-2-yl)ethyl
      fragment (J. Org. Chem. ASAP Doi:10.1021/jo401674v) of (N-(2-methylpropyl)-N-(1
      diethylphosphono-2,2-dimethylpropyl)-N-oxyl) SG1-based alkoxyamines. The
      quaternization of the 1-(pyridin-3-yl)ethyl fragment by the aforementioned
      reactions was investigated for the corresponding SG1-based alkoxyamines. In sharp
      contrast to the quaternization at ortho and para positions of the pyridyl moiety,
      the effect of the quaternization at the meta position was weak. The effects of
      quaternization at ortho, meta and para positions were investigated through
      natural bond orbital and Mulliken charges, HOMO-LUMO interactions in the starting
      materials and the radical stabilization energy of the released 1-puridylmethyl
      radicals using DFT calculations with the B3LYP/6-31G(d) and UBMK/6
      311+G(3df,2p)//R(O)B3LYP/6-31G(d) methods, respectively. 

PMID- 24114040
TI  - Regulation of deleted in liver cancer 1 tumor suppressor by protein-protein
      interactions and phosphorylation.
AB  - The deleted in liver cancer 1 (DLC1) tumor suppressor is an important RhoGTP
      activating protein (RhoGAP) that plays a crucial role in many types of human
      cancers. Small GTPases regulate normal cellular processes but aberrant expression
      and activation of GTPases contribute to tumorigenesis. RhoGAP suppresses Rho
      activity. DLC1's RhoGAP activity and the focal adhesion localization are critical
      to the tumor suppressor functions of DLC1. Frequent DLC1 underexpression is
      commonly seen in human cancers and has been ascribed to genomic deletion and
      epigenetic inactivation. Somatic mutation has been shown to deregulate the RhoGAP
      activity of DLC1. Deregulation of DLC1 in cells results in the elevation of
      active Rho. Compelling studies of the molecular mechanisms of DLC1 action have
      identified various interacting partners of DLC1 such as tensins and caveolin-1,
      and revealed the associated signaling pathways. DLC1 has been shown to be a
      promiscuous interacting protein. Recent interest has also focused on the
      phosphorylation of DLC1. The upstream kinases such as PKA, PKB/Akt and PKC, and
      the effects of phosphorylation on the biological activities of DLC1 have been
      demonstrated. Although DLC1 is a RhoGAP, RhoGAP-independent pathways have been
      involved via its interacting partners and upon phosphorylation regulation. Recent
      studies of DLC1 point to the complexity of the signaling pathways it regulates.
      This review summarizes the current understanding of the interacting potentials of
      DLC1 and phosphorylation of DLC1. 

PMID- 24114041
TI  - If you have a low adenoma detection rate, don't blame your fellows.

PMID- 24114039
TI  - Environmental chemicals and type 2 diabetes: an updated systematic review of the
      epidemiologic evidence.
AB  - The burden of diabetes is increasing globally. Identifying novel preventable risk
      factors is an urgent need. In 2011, the U.S. National Toxicological Program (NTP)
      conducted a workshop to evaluate the epidemiologic and experimental evidence on
      the relationship of environmental chemicals with obesity, diabetes, and metabolic
      syndrome. Although the evidence was insufficient to establish causality, the NTP
      workshop review identified an overall positive association between some
      environmental chemicals and diabetes. In the present systematic review, our
      objective was to summarize the epidemiological research published since the NTP
      workshop. We identified a total of 29 articles (7 on arsenic, 3 on cadmium, 2 on
      mercury, 11 on persistent organic pollutants, 3 on phthalates, and 4 on bisphenol
      A), including 7 prospective studies. Considering consistency, temporality,
      strength, dose-response relationship, and biological plausibility (confounding),
      we concluded that the evidence is suggestive but not sufficient for a
      relationship between arsenic and persistent organic pollutants and is
      insufficient for mercury, phthalates, and bisphenol A. For cadmium, the
      epidemiologic evidence does not seem to suggest an association with diabetes.
      Important research questions include the need for additional prospective studies
      and the evaluation of the dose-response relationship, the role of joint
      exposures, and effect modification with other comorbidities and genetic variants.

PMID- 24114042
TI  - Nitric oxide synthase gene polymorphisms in functional dyspepsia.
AB  - OBJECTIVE: Nitrinergic control is important in meal-induced satiety. The aim of
      this study was to assess functional polymorphisms in nitric oxide synthase (NOS)
      genes in the susceptibility to functional dyspepsia (FD). METHODS: Genomic DNA
      from 89 patients with FD and 180 healthy subjects matched for age and gender were
      typed for the gene of neuronal NOS (nNOS, rs2682826), inducible NOS (iNOS,
      rs2297518) and a variable number tandem repeat in intron 4 of endothelial NOS
      (eNOS). Patients ingested 500 mL of Ensure((r)) during a 20 min period and
      dyspeptic symptoms were scored. RESULTS: Genotype frequencies of eNOS and iNOS
      were not significantly different between FD patients and controls. The frequency
      of the T allele in nNOS was significantly higher in FD patients compared to the
      controls (49 vs. 16 %; odds ratio 5.01; 95 % confidence interval 2.83-9.01; p <
      0.05). Patients with the T allele in the nNOS polymorphism reported a higher
      satiation score than those with the CC genotype during the nutrition drink test
      (median 179 vs. 117; p < 0.05). CONCLUSION: The nNOS gene polymorphism is
      associated with susceptibility to FD and influences satiation in FD patients. Our
      data support the importance of NOS gene polymorphisms in the pathogenesis of FD.

PMID- 24114043
TI  - MicroRNAs in gastric cancer: from benchtop to bedside.
AB  - Gastric carcinogenesis represents a stepwise progression from chronic
      inflammation to invasive adenocarcinomas and distant metastasis. It has been
      widely accepted that these pathologic changes are contributed by aberrant
      activation or inactivation of protein-coding proto-oncogenes and tumor suppressor
      genes. However, recent discoveries in microRNA research have reshaped our
      understanding of the role of non-protein-coding genes in carcinogenesis.
      MicroRNAs (miRNAs) are a family of 18-25-nucleotide small RNAs that negatively
      regulate gene expression at the post-transcriptional level during various crucial
      cell processes such as apoptosis, differentiation and development. Changes in
      miRNA expression profiles have been observed in a variety of human tumors,
      including gastric cancer. Further studies demonstrated that miRNAs may function
      as tumor suppressors and oncogenes. These findings have shown great potential of
      miRNAs as a novel class of therapeutic targets. In addition, it was found that
      some miRNAs were directly involved in patients with gastric cancer, including
      prognosis prediction, treatment selection, and in the search for unknown primary
      sites. MiRNAs have also been proved to be detectable in serum and plasma. In this
      review, we summarize the function of miRNAs in gastric cancer. Furthermore, we
      describe the pathophysiological roles of these miRNAs and their clinical
      potential as diagnostic biomarkers and therapeutic targets.

PMID- 24114044
TI  - Fibrocytes, inflammation, and fibrosis in Crohn's disease: another piece of the
      puzzle.

PMID- 24114045
TI  - Impaired sleep quality in Crohn's disease depends on disease activity.
AB  - BACKGROUND: Little is known concerning the relationship of disease activity and
      sleep disturbances in inflammatory bowel disease (IBD) and specifically in
      patients with Crohn's disease. AIM: This study examined the prevalence of poor
      sleep quality in patients with active and inactive Crohn's disease compared with
      healthy controls. METHODS: Participants included 108 patients with Crohn's
      disease attending the IBD clinic of a tertiary medical center in 2009-2010 and 36
      healthy volunteers. All prospectively completed a demographic questionnaire and
      the Pittsburgh sleep quality index (PSQI). Patients with Crohn's disease
      completed the Crohn's disease activity index (CDAI) and were divided into two
      groups accordingly: inactive disease (CDAI <=150) and active disease (CDAI >150).
      Data on disease duration, medications, complications, and treatment were
      collected from the medical files. RESULTS: Seventy-one patients had inactive
      Crohn's disease and 37 had active disease. All three groups were similar in mean
      age, sex distribution, and body mass index. Mean duration of Crohn's disease was
      10.22 +/- 8.6 years; 40 patients (37 %) had ileal disease, 16 (15 %) colonic
      disease, and 56 (50 %) ileo-colonic disease. Patients with active disease had a
      significantly higher mean +/- SD global score on the PSQI (8.6 +/- 2.4;
      indicating poorer sleep quality) than patients with inactive disease (4.6 +/-
      1.9) or control subjects (5.1 +/- 1.7) (p < 0.0001 for both), with no significant
      difference between the inactive-disease and control groups. The correlation
      between the CDAI and PSQI scores was statistically significant (p < 0.001).
      CONCLUSIONS: Impaired sleep quality is associated with active Crohn's disease,
      but not inactive disease.

PMID- 24114047
TI  - Primary sclerosing cholangitis in the setting of normal liver chemistries can be
      associated with severe ductal disease and dominant strictures.

PMID- 24114046
TI  - No significant effects of smoking or alcohol consumption on risk of Barrett's
      esophagus.
AB  - BACKGROUND: Smoking, but not higher alcohol consumption, is associated with
      increased risk of esophageal adenocarcinoma (EAC) and progression from Barrett's
      esophagus (BE) to EAC. However, it is still unclear whether smoking or alcohol is
      implicated in the development of BE. AIM: To evaluate the associations between
      smoking, alcohol and the risk of BE. METHODS: The study included eligible
      patients scheduled for elective esophagogastroduodenoscopy (EGD) and a sample of
      patients eligible for screening colonoscopy recruited from primary care clinics.
      We compared 258 patients with definitive BE with two separate control groups: 453
      patients from the primary care group ("colonoscopy controls") and 1,145 patients
      from the elective EGD group ("endoscopy controls") with no endoscopic or
      histopathologic BE. We calculated odds ratios (OR) and 95 % confidence intervals
      (95 % CI) using multivariable logistic regression models. RESULTS: Seventy-seven
      percent of BE cases, 75 % of colonoscopy controls and 72 % of endoscopy controls
      were ever smokers. Of these, approximately 45 % were current smokers. Overall, 91
      % of study participants were ex or current alcohol drinkers, with the majority
      drinking beer. We found no association between various measure of smoking
      exposure (status, intensity, age at initiation, duration, pack-years and
      cessation) and risk of BE. Alcohol consumption was not associated with increased
      risk of BE. Conversely, moderate intake was associated with lower risk (14 to <28
      drinks/week, OR 0.39, 95 % CI 0.15-1.00). CONCLUSION: Smoking and alcohol were
      not strong or consistent risk factors for BE. The likely role of smoking in
      increasing risk of EAC is through promoting progression from BE to cancer.

PMID- 24114048
TI  - First reported case of intentional use of a duodenal stent to treat gastric
      outlet obstruction prior to pancreaticoduodenectomy in a patient with pancreatic
      cancer.

PMID- 24114049
TI  - Sustained virological response after 4 weeks of telaprevir, peginterferon, and
      ribavirin in an Asian patient with genotype 1 chronic hepatitis C and IL28B
      genotype CC.

PMID- 24114051
TI  - Genetic analysis and molecular mapping of low amylose gene du12(t) in rice (Oryza
      sativa L.).
AB  - KEY MESSAGE: We obtained interesting results for genetic analysis and molecular
      mapping of the du12(t) gene. Control of the amylose content in rice is the major
      strategy for breeding rice with improved quality. In this study, we conducted
      genetic analysis and molecular mapping to identify the dull gene in the dull
      rice, Milyang262. A single recessive gene, tentatively designated as du12(t), was
      identified as the dull gene that leads to the low amylose character of
      Milyang262. To investigate the inheritance of du12(t), genetic analysis on an F2
      population derived from a cross between the gene carrier, Milyang262, and a
      moderate amylose content variety, Junam, was conducted. A segregation ratio of
      3:1 (chi (2) = 1.71, p = 0.19) was observed, suggesting that du12(t) is a single
      recessive factor that controls the dull character in Milyang262. Allelism tests
      confirmed that du12(t) is not allelic to other low amylose controlling genes, wx
      or du1. Recessive class analysis was performed to localize the du12(t) locus.
      Mapping of du12(t) was conducted on F2 and F3 populations of
      Baegokchal/Milyang262 cross. Linkage analysis of 120 F2 plants revealed that
      RM6926 and RM3509 flank du12(t) at a 2.38-Mb region. To refine the du12(t) locus
      position, 986 F2 and 289 F3 additional normal plants were screened by the
      flanking markers. Twenty-six recombinant plants were identified and later
      genotyped with four additional adjacent markers located between RM6926 and
      RM3509. Finally, du12(t) was mapped to an 840-kb region on the distal region of
      the long arm of chromosome 6, delimited by SSR markers RM20662 and RM412, and co
      segregated by RM3765 and RM176.

PMID- 24114050
TI  - Association mapping, patterns of linkage disequilibrium and selection in the
      vicinity of the PHYTOCHROME C gene in pearl millet.
AB  - KEY MESSAGE: Linkage analysis confirmed the association in the region of PHYC in
      pearl millet. The comparison of genes found in this region suggests that PHYC is
      the best candidate. Major efforts are currently underway to dissect the phenotype
      genotype relationship in plants and animals using existing populations. This
      method exploits historical recombinations accumulated in these populations.
      However, linkage disequilibrium sometimes extends over a relatively long
      distance, particularly in genomic regions containing polymorphisms that have been
      targets for selection. In this case, many genes in the region could be
      statistically associated with the trait shaped by the selected polymorphism.
      Statistical analyses could help in identifying the best candidate genes into such
      a region where an association is found. In a previous study, we proposed that a
      fragment of the PHYTOCHROME C gene (PHYC) is associated with flowering time and
      morphological variations in pearl millet. In the present study, we first
      performed linkage analyses using three pearl millet F2 families to confirm the
      presence of a QTL in the vicinity of PHYC. We then analyzed a wider genomic
      region of ~100 kb around PHYC to pinpoint the gene that best explains the
      association with the trait in this region. A panel of 90 pearl millet inbred
      lines was used to assess the association. We used a Markov chain Monte Carlo
      approach to compare 75 markers distributed along this 100-kb region. We found the
      best candidate markers on the PHYC gene. Signatures of selection in this region
      were assessed in an independent data set and pointed to the same gene. These
      results foster confidence in the likely role of PHYC in phenotypic variation and
      encourage the development of functional studies.

PMID- 24114052
TI  - Perioperative antimicrobial prophylaxis for intra-abdominal surgery in patients
      with cancer: a retrospective study comparing ertapenem and nonertapenem
      antibiotics.
AB  - BACKGROUND: To evaluate the role of ertapenem versus other standard antibiotic
      prophylaxis in patients with cancer undergoing intra-abdominal surgery. METHODS:
      Our study was a retrospective cohort study consisting 615 patients who underwent
      intra-abdominal surgery at our institution between January 2007 and December
      2010. The groups were divided among patients who received ertapenem as
      perioperative prophylaxis (ertapenem group) and patients who received other
      antibiotics (nonertapenem group). Groups were similar with respect to age,
      gender, and type of surgery. RESULTS: A total of 315 patients underwent
      colorectal and 300 noncolorectal surgeries. In a multivariate logistic regression
      model, the main factors associated with risk of surgical site infections (SSI)
      were as follows: antibiotics within 3 months of surgery (odds ratio [OR] 1.2, 95%
      confidence interval [CI] 1.04-1.54; p = 0.05), prior hospitalization within 1
      year (OR 1.21, 95% CI 1.02-1.43; p = 0.05), diabetes mellitus (OR 2.1, 95% CI 1.7
      3.4; p = 0.04), and perioperative prophylaxis other than ertapenem (OR 1.7, 95%
      CI 1.2-2.3; p = 0.04). Notably, patients who underwent colorectal surgery and
      received ertapenem had a lower rate of SSI (4% ertapenem vs. 13% nonertapenem, p
      = 0.01), whereas the frequency of infections was not different in patients who
      underwent other intra-abdominal surgery whether they received ertapenem or not.
      CONCLUSIONS: The use of ertapenem for perioperative prophylaxis in patients with
      colorectal surgery was associated with lower rates of SSI, while there was no
      difference in rates of infection in other intra-abdominal surgery.

PMID- 24114053
TI  - Intensity of follow-up after melanoma surgery.
AB  - This contemporary review of melanoma surveillance strategies seeks to help
      practitioners examine and improve their surveillance protocols based on the
      currently available data. In general, there is no definitive benefit from
      increased screening or more aggressive use of interval imaging. Low-intensity
      surveillance strategies do not appear to adversely affect patient outcomes and
      should be the preferred approach compared with high-intensity strategies for most
      melanoma patients. All surveillance programs should emphasize education in order
      to maximize the effectiveness of patient-based detection of recurrent disease. 

PMID- 24114054
TI  - Review of the impact of antineoplastic therapies on the risk for cholelithiasis
      and acute cholecystitis.
AB  - BACKGROUND: Development of cholecystitis in patients with malignancies can
      potentially disrupt their treatment and alter prognosis. This review aims to
      identify antineoplastic interventions associated with increased risk of
      cholecystitis in cancer patients. METHODS: A comprehensive search strategy was
      developed to identify articles pertaining to risk factors and complications of
      cholecystitis in cancer patients. FDA-issued labels of novel antineoplastic drugs
      released after 2010 were hand-searched to identify more therapies associated with
      cholecystitis in nonpublished studies. RESULTS: Of an initial 2,932 articles, 124
      were reviewed in the study. Postgastrectomy patients have a high (5-30 %)
      incidence of gallstone disease, and 1-7 % develop symptomatic disease. One
      randomized trial addressing the role of cholecystectomy concurrent with
      gastrectomy is currently underway. Among other risk groups, patients with
      neuroendocrine tumors treated with somatostatin analogs have a 15 % risk of
      cholelithiasis, and most are symptomatic. Hepatic artery based therapies carry a
      risk of cholecystitis (0.02-24 %), although the risk is reduced with selective
      catheterization. Myelosuppression related to chemotherapeutic agents (0.4 %),
      bone marrow transplantation, and treatment with novel multikinase inhibitors are
      associated with high risk of cholecystitis. CONCLUSIONS: There are several risk
      factors for gallbladder-related surgical emergencies in patients with advanced
      malignancies. Incidental cholecystectomy at index operation should be considered
      in patients planned for gastrectomy, and candidates for regional therapies to the
      liver or somatostatin analogs. While prophylactic cholecystectomy is currently
      recommended for patients with cholelithiasis receiving myeloablative therapy,
      this strategy may have value in patients treated with multikinase inhibitors,
      immunotherapy, and oncolytic viral therapy based on evolving evidence.

PMID- 24114055
TI  - AQP5 expression predicts survival in patients with early breast cancer.
AB  - BACKGROUND: Our previous study showed the association of aquaporin 5 (AQP5) up
      regulation with cancer proliferation and migration in estrogen receptor (ER)
      positive breast cancer cell line (MCF-7) and with unfavorable prognosis in a
      small number of patients with breast cancer. Accordingly, we analyzed the
      prognostic impact of AQP5 expression in a large number of patients with early
      breast cancer (EBC). METHODS: AQP5 expression was investigated on the basis of
      the immunohistochemistry of tissue microarray specimens from 447 EBC patients who
      underwent surgery between 2003 and 2008. We scored the staining intensity (0
      through 3) and percentage of positive tumor cells (0 through 4), and the staining
      score was defined as sum of these scores used to categorize the AQP5 expression
      as negative (0 through 2), weak (3 through 5), or strong (6 or more). RESULTS: A
      total of 267 (59.7%) patients were identified as AQP5-positive (staining score
      >2), including 123 (27.5%) cases of strong expression (stating score >5). In a
      univariate analysis, AQP5 overexpression was significantly associated with
      survival for the patients with ER/progesterone receptor (PR)-positive and human
      epidermal growth factor receptor 2 (HER2)-overexpressed EBC. Moreover, a
      multivariate survival analysis revealed that AQP5 overexpression was an
      independent prognostic marker of survival for the EBC patients, which was
      prominent in patients with ER/PR-positive tumor. However, no difference in AQP5
      expression was observed on the basis of patient and tumor characteristics.
      CONCLUSIONS: AQP5 expression in tumor tissue can be considered a prognostic
      marker in patients with EBC after curative surgery.

PMID- 24114057
TI  - Dysregulation of Treg cells in antineutrophil cytoplasmic antibody-associated
      vasculitis: comment on the article by Free et al.

PMID- 24114056
TI  - Overexpression of membrane proteins in primary and metastatic gastrointestinal
      neuroendocrine tumors.
AB  - BACKGROUND: Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs)
      are rare tumors whose incidence is increasing. Drugs targeting the somatostatin
      receptor are beneficial in these tumors. To identify additional cell-surface
      targets, we recently found receptors and membrane proteins with gene expression
      significantly different from adjacent normal tissues in a small number of primary
      SBNETs and PNETs. We set out to validate these expression differences in a large
      group of primary neuroendocrine tumors and to determine whether they are present
      in corresponding liver and lymph node metastases. METHODS: Primary SBNETs and
      PNETs, normal tissue, nodal, and liver metastases were collected and mRNA
      expression of six target genes was determined by quantitative PCR. Expression was
      normalized to GAPDH and POLR2A internal controls, and differences as compared to
      normal tissue were assessed by Welch's t test. RESULTS: Gene expression was
      determined in 45 primary PNETs with 20 nodal and 17 liver metastases, and 51
      SBNETs with 50 nodal and 29 liver metastases. Compared to normal tissue, the
      oxytocin receptor (OXTR) showed significant overexpression in both primary and
      metastatic SBNETs and PNETs. Significant overexpression was observed for MUC13
      and MEP1B in PNET primary tumors, and for GPR113 in primary SBNETs and their
      metastases. SCTR and ADORA1 were significantly underexpressed in PNETs and their
      metastases. OXTR protein expression was confirmed by immunohistochemistry.
      CONCLUSIONS: OXTR is significantly overexpressed relative to normal tissue in
      primary SBNETs and PNETs, and this overexpression is present in their liver and
      lymph node metastases, making OXTR a promising target for imaging and therapeutic
      interventions.

PMID- 24114058
TI  - Neuroprotective efficacy of prophylactic enteral and parenteral nimodipine
      treatment in vestibular schwannoma surgery: a comparative study.
AB  - BACKGROUND AND STUDY AIMS/OBJECT: Oral nimodipine improves neurologic outcome
      after aneurysmal subarachnoid hemorrhage. In addition, the neuroprotective
      efficacy of nimodipine has been revealed following skull base, laryngeal, and
      maxillofacial surgery. Pharmacokinetic investigations showed nimodipine to reach
      higher serum levels following parenteral versus enteral administration.
      Furthermore, a correlation between nimodipine levels in serum, cerebrospinal
      fluid, and nerve tissue could be quantified. These observations raise the
      question whether the proven neuroprotective effect of nimodipine is related to
      its serum level. PATIENTS/MATERIAL AND METHODS: A consecutive series of 37
      patients with vestibular schwannoma treated with nimodipine from the day before
      surgery until the seventh postoperative day was analyzed retrospectively. Both
      groups received standard dosages for enteral (n = 17) and parenteral (n = 20)
      nimodipine medication. Nimodipine levels were measured in pre- and postoperative
      serum and cerebrospinal fluid samples. Cochlear and facial nerve functions were
      documented before surgery, in the early postoperative course, and 1 year after
      surgery. RESULTS: Facial nerve outcome was significantly better in the group with
      parenteral nimodipine medication (p = 0.038). Logistical regression analysis
      revealed a seven times smaller risk for a deterioration of facial nerve function
      in the group with parenteral treatment. There was no difference in hearing
      preservation between both groups despite tumor size tending to be larger in the
      parenteral group. Intraoperative (p = 0.004), postoperative (p = 0.001), and
      serum and cerebrospinal fluid (p = 0.024) nimodipine levels were significantly
      higher following parenteral administration as compared with enteral
      administration. Both groups were comparable regarding tumor size and extent of
      resection. CONCLUSIONS: These results support a dependency of nimodipine's
      neuroprotective efficacy on its serum levels. Parenteral nimodipine treatment
      produces higher serum levels and has a higher neuroprotective potency in
      vestibular schwannoma surgery compared with enteral treatment.

PMID- 24114059
TI  - Absorption and bioavailability of antioxidant phytochemicals and increase of
      serum oxidation resistance in healthy subjects following supplementation with
      raisins.
AB  - The aim of this study was to examine the postprandial impact of raisin
      supplementation in serum resistance to oxidation of healthy subjects, to quantify
      the bioavailable phenolic compounds and oleanolic acid. The content of
      phytochemicals in raisins was determined by GC-MS. Fifteen healthy volunteers who
      consumed 144 g of raisins were subjected to blood collection at time 0 and 1, 2,
      3 and 4 h after consumption. Blood samples were used for the quantification of
      (a) serum oxidizability (b) plasma total polyphenol content and (c) phenolic
      compounds and oleanolic acid by applying GC-MS analysis. A total of 25
      phytochemicals were identified and quantified in raisins, while the triterpenoid
      oleanolic acid was present at the highest concentration. The peak of plasma total
      phenolics and serum oxidation resistance appeared 1 h after raisin
      supplementation (p < 0.05) and correlated strongly with each other. Seventeen
      phytochemicals (16 phenolics and oleanolic acid) were clearly identified and
      quantified in volunteers' plasma. Each compound followed different kinetics,
      however 13 out of 17 peaked in plasma also 1 h after supplementation. The results
      indicate that raisins influence antioxidant potential in vivo, while the
      contained phytochemicals are bioavailable. 

PMID- 24114060
TI  - Roles of BOR2, a boron exporter, in cross linking of rhamnogalacturonan II and
      root elongation under boron limitation in Arabidopsis.
AB  - Boron (B) is required for cross linking of the pectic polysaccharide
      rhamnogalacturonan II (RG-II) and is consequently essential for the maintenance
      of cell wall structure. Arabidopsis (Arabidopsis thaliana) BOR1 is an efflux B
      transporter for xylem loading of B. Here, we describe the roles of BOR2, the most
      similar paralog of BOR1. BOR2 encodes an efflux B transporter localized in plasma
      membrane and is strongly expressed in lateral root caps and epidermis of
      elongation zones of roots. Transfer DNA insertion of BOR2 reduced root elongation
      by 68%, whereas the mutation in BOR1 reduced it by 32% under low B availability
      (0.1 um), but the reduction in shoot growth was not as obvious as that in the
      BOR1 mutant. A double mutant of BOR1 and BOR2 exhibited much more severe growth
      defects in both roots and shoots under B-limited conditions than the
      corresponding single mutants. All single and double mutants grew normally under B
      sufficient conditions. These results suggest that both BOR1 and BOR2 are required
      under B limitation and that their roles are, at least in part, different. The
      total B concentrations in roots of BOR2 mutants were not significantly different
      from those in wild-type plants, but the proportion of cross-linked RG-II was
      reduced under low B availability. Such a reduction in RG-II cross linking was not
      evident in roots of the BOR1 mutant. Thus, we propose that under B-limited
      conditions, transport of boric acid/borate by BOR2 from symplast to apoplast is
      required for effective cross linking of RG-II in cell wall and root cell
      elongation. 

PMID- 24114061
TI  - Gentamicin conditioning confers auditory protection against noise trauma.
AB  - Auditory conditioning consists of the pre-exposure to low levels of a potential
      harmful agent to protect against a subsequent harmful presentation. The agent
      that was first tested was noise. This paradigm was more recently successfully
      tested with other agents. Nonetheless, the vast majority of the studies utilize
      the same agent to condition and to cause the trauma. The aim of this study was to
      verify whether conditioning with an agent different from the agent used to cause
      the trauma can also be effective. Thus, the following groups were organized:
      group Cont, which is the noise trauma control group, was exposed to 110-dB
      broadband noise centered at 4 kHz for 72 h; group Gent, which is the gentamicin
      conditioning control group, was administered 30 mg/kg of gentamicin daily for 30
      consecutive days; and group Expt was conditioned with gentamicin similarly to
      group Gent and then subjected to a noise trauma similarly to group Cont. The
      animals were functionally and morphologically evaluated through the measurement
      of the auditory brainstem response and scanning electron microscopy,
      respectively. The following variables were investigated: outer hair cell injury
      and auditory threshold shift. The group that was conditioned with the drug
      exhibited significantly less outer hair cell damage, 10.8 and 22.9%, respectively
      (p = 0.0146), although did not maintain the proper functioning of the auditory
      system. We, therefore, conclude that conditioning with a different agent from
      that used to cause the trauma is effective, which suggests that both agents that
      were used promote similar mechanisms of self-protection.

PMID- 24114062
TI  - Incidence and localization of abnormal mucosa findings in patients consulting ENT
      outpatient clinics and data analysis of a cancer registry.
AB  - For patients without symptoms and at risk, there is no established early
      detection program to discover carcinomas of the upper aerodigestive tract in the
      sense of secondary prevention. Such type of prevention seems even more desirable
      because the chances for a cure and the quality of life are strongly dependent on
      the stage of the tumor and the time of the initial diagnosis. Six hundred and
      eight patients without symptoms but at least one of the self-reported risk
      factors "smoking", "alcohol consumption" or "reflux" were examined with an
      endoscope or an optical microscope for pathological findings in the upper
      aerodigestive tract once a year. In addition, the incidence of malignancies of
      the upper aerodigestive tract between 2001 and 2010 was determined through the
      Cancer Registry of Schleswig-Holstein. Tissue samples were taken from 18 of the
      608 patients. Eleven patients (1.8%) had a squamous cell carcinoma. Another
      patient suffered from non-Hodgkin's lymphoma and one from larynx tuberculosis.
      The ratio of detected malignancies in the oral cavity and the oropharynx on the
      one hand and the hypopharynx and larynx, which can only be examined by
      endoscopes, on the other hand were in our cohorts and in our survey according to
      the cancer registry was 5/6. The above-described methods allow examining risk
      patients easily and safely. According to current publications, the ratio of the
      found malignancies exceeds the expected ratio significantly, which presumably was
      caused by the examination targeting patients at risk. Due to the expanded
      examination area using optical instruments more than doubles the rate of
      discoverable malignancies compared to the limitations posed by the examination of
      directly visible areas of the oral cavity of the oropharynx.

PMID- 24114063
TI  - Assessment of functional outcomes in head and neck cancer.
AB  - The goals of the present publication are (a) to identify standardised methods and
      tools applied in clinical trials and cohort studies to assess key functional
      aspects in HNC, using the Brief ICF Core Set for head and neck cancer (ICF-HNC)
      as a reference and (b) to propose a set of sound standardised methods and tools
      suitable to assess functional problems in HNC. This work contributed to the
      development of practical ICF-HNC based guidelines targeting the standardised
      measurement of functional outcomes in HNC follow-up and clinical research in
      Germany. A systematic review of randomised and clinical controlled trials, and
      observational studies in HNC were carried out to identify standardised methods
      and tools. Suitable methods and tools were then selected based on pre-defined
      criteria. 210 assessment methods and tools were identified in 136 studies: 146
      patients reported outcomes (PRO) and 64 tools rated by health professionals.
      Altogether 59 tools were considered suitable to be included in guidelines: four
      side effects classifications, two performance status scales, 31 PROs, 10
      assessment criteria for clinical examinations, seven assessment methods and tools
      for the evaluation of technical, equipment-based procedures and five technical,
      equipment-based procedures. It was possible to identify and select sound and
      standardised assessment methods and tools for almost all functioning areas
      defined in the ICF-HNC. Since no tool sufficiently covers support provision by
      immediate family and by health professionals as well as economic self
      sufficiency, we recommend a corresponding update of existing tools. 

PMID- 24114064
TI  - Oval and round window vibroplasty: a comparison of hearing results, risks and
      failures.
AB  - The aim of this study was to compare oval and round window vibroplasty. Eighteen
      (18) patients implanted with Vibrant Soundbridge (VSB) were enrolled. Two groups
      were formed depending on FMT placement: on round window in ten cases (RW group)
      and on oval window in eight (OW group). Pre and postoperative audiological tests
      were performed both under headphones and free-field settings, VSB on and off. One
      (1) RW patient experienced sudden hearing loss at the operated side after 4
      months from surgery and was excluded from the analysis. Both groups showed good
      hearing results. Significant differences were measured at free-field pure-tone
      test with VSB on at 0.5 kHz (RW better than OW, p = 0.026) and 4 kHz (OW better
      than RW, p = 0.043). Both techniques share similar good results and are
      considered safe. However, we had one failure with deep and sudden hearing
      threshold worsening after some months of good results. From a surgical point of
      view OW vibroplasty is easier and safer to perform, when the stapes
      suprastructure is absent, as it does not require any drilling and should be
      preferred in such cases. More reports are needed to explain if RW vibroplasty is
      risky in a mid to long term.

PMID- 24114065
TI  - Vasospasm of labyrinthine artery in cerebellopontine angle surgery: evidence
      brought by distortion-product otoacoustic emissions.
AB  - In cerebellopontine angle (CPA) surgery, postoperative deafness can be due to
      alteration of cochlear blood flow that is supplied by the labyrinthine artery
      (LA). In particular, vasospasm is likely to occur and, if so, can be reversed.
      This work attempted to track down vascular events occurring during CPA surgery.
      Twenty consecutive patients with vestibular schwannoma were tested with useful
      preoperative hearing and presence of otoacoustic emissions (OAEs). Distortion
      product otoacoustic emissions (DPOAEs), well-known to react within seconds to
      cochlear ischemia, were used intraoperatively to indirectly monitor cochlear
      blood flow. Continuous intraoperative monitoring of DPOAEs revealed three
      different time patterns associated with distinct auditory outcomes. Pattern P1
      acute (n = 4) happened when the LA was severed: DPOAEs immediately and
      irreversibly foundered and led to postoperative deafness. Pattern P2-protracted
      (n = 7) revealed a progressive deterioration of DPOAEs from the beginning of
      tumor debulking, likely due to a steady decrease of cochlear blood flow, with
      postoperative deafness. Pattern P3-unstable (n = 5) corresponded to large DPOAE
      oscillations between their normal level and noise floor. It was due to acute LA
      vasospasm that could be reversed in three cases by topical nimodipin. Last, four
      patients had uneventful cochlear monitoring. In conclusion, cochlear ischemia can
      occur in vestibular schwannoma surgery, giving three different patterns among
      which vasospasm can be reversed if detected early.

PMID- 24114066
TI  - A longitudinal study of changes in distortion-product otoacoustic emissions and
      pure-tone thresholds in an industrial setting.
AB  - In a longitudinal study of 76 noise-exposed industrial workers, 34 (68 ears) of
      them were available for final evaluation after 9 years of observation. Distortion
      product otoacoustic emissions (DP) at 65/55 dB SPL and pure-tone audiometry were
      used to detect noise-induced inner ear changes. Repeated measures analyses of
      variance were made on the subjects and in a control group, whereas significant
      threshold shifts (STS) and significant emission shifts (SES) were calculated.
      Both hearing thresholds and DP showed a high-frequency deterioration, but there
      was absence of statistical correlation between elevation of hearing thresholds
      and decrease of DP. There was no clear pattern between individual changes in
      audiometric thresholds and DP, and all combinations were present: ears with only
      STS, ears with only SES, ears with both STS and SES and ears with absence of STS
      and SES. Audiometric changes were maximal at 4 and 6 kHz and DP changes at 2 and
      3 kHz. Since significant individual emission changes do not necessarily follow
      the same pattern as the group-averaged results, the use of DP for monitoring of
      individual subjects is not advised. However, its use in conjunction with
      audiometry in hearing conservation programs is highly recommended.

PMID- 24114067
TI  - Use of a microsecond Er:YAG laser in laryngeal surgery reduces collateral thermal
      injury in comparison to superpulsed CO2 laser.
AB  - Despite causing significant thermocoagulative insult, use of the carbon dioxide
      (CO2) laser is considered gold standard in surgery for early stage larynx
      carcinoma. Limited attention has been paid to the use of the erbium:yttrium
      aluminium-garnet (Er:YAG) laser in laryngeal surgery as a means to reduce thermal
      tissue injury. The objective of this study is to compare the extent of thermal
      injury and precision of vocal fold incisions made using microsecond Er:YAG and
      superpulsed CO2 lasers. In the optics laboratory ex vivo porcine vocal folds were
      incised using Er:YAG and CO2 lasers. Lateral epithelial and subepithelial thermal
      damage zones and cutting gap widths were histologically determined. Environmental
      scanning electron microscopy (ESEM) images were examined for signs of
      carbonization. Temperature rise during Er:YAG laser incisions was determined
      using infrared thermography (IRT). In comparison to the CO2 laser, Er:YAG laser
      incisions showed significantly decreased epithelial (236.44 MUm) and
      subepithelial (72.91 MUm) damage zones (p < 0.001). Cutting gaps were
      significantly narrower for CO2 (878.72 MUm) compared to Er:YAG (1090.78 MUm; p =
      0.027) laser. ESEM revealed intact collagen fibres along Er:YAG laser cutting
      edges without obvious carbonization, in comparison to diffuse carbonization and
      tissue melting seen for CO2 laser incisions. IRT demonstrated absolute
      temperature rise below 70  degrees C for Er:YAG laser incisions. This study has
      demonstrated significantly reduced lateral thermal damage zones with wider basal
      cutting gaps for vocal fold incisions made using Er:YAG laser in comparison to
      those made using CO2 laser. 

PMID- 24114068
TI  - Efficient parameter estimation for models of healthcare-associated pathogen
      transmission in discrete and continuous time.
AB  - We describe two novel Markov chain Monte Carlo approaches to computing estimates
      of parameters concerned with healthcare-associated infections. The first approach
      frames the discrete time, patient level, hospital transmission model as a
      Bayesian network, and exploits this framework to improve greatly on the
      computational efficiency of estimation compared with existing programs. The
      second approach is in continuous time and shares the same computational
      advantages. Both methods have been implemented in programs that are available
      from the authors. We use these programs to show that time discretization can lead
      to statistical bias in the underestimation of the rate of transmission of
      pathogens. We show that the continuous implementation has similar running time to
      the discrete implementation, has better Markov chain mixing properties, and
      eliminates the potential statistical bias. We, therefore, recommend its use when
      continuous-time data are available. 

PMID- 24114069
TI  - A new phosphorus paradigm for the Baltic proper.
AB  - The external phosphorus (P) loading has been halved, but the P content in the
      water column and the area of anoxic bottoms in Baltic proper has increased during
      the last 30 years. This can be explained by a temporary internal source of
      dissolved inorganic phosphorus (DIP) that is turned on when the water above the
      bottom sediment becomes anoxic. A load-response model, explaining the evolution
      from 1980 to 2005, suggests that the average specific DIP flux from anoxic
      bottoms in the Baltic proper is about 2.3 g P m-2 year-1. This is commensurable
      with fluxes estimated in situ from anoxic bottoms in the open Baltic proper and
      from hydrographic data in the deep part of Bornholm Basin. Oxygenation of anoxic
      bottoms, natural or manmade, may quickly turn off the internal P source from
      anoxic bottoms. This new P-paradigm should have far-reaching implications for
      abatement of eutrophication in the Baltic proper.

PMID- 24114070
TI  - Evidence of large-scale chronic eutrophication in the Great Barrier Reef:
      quantification of chlorophyll a thresholds for sustaining coral reef communities.
AB  - Long-term monitoring data show that hard coral cover on the Great Barrier Reef
      (GBR) has reduced by >70 % over the past century. Although authorities and many
      marine scientists were in denial for many years, it is now widely accepted that
      this reduction is largely attributable to the chronic state of eutrophication
      that exists throughout most of the GBR. Some reefs in the far northern GBR where
      the annual mean chlorophyll a (Chl a) is in the lower range of the proposed
      Eutrophication Threshold Concentration for Chl a (~0.2-0.3 mg m-3) show little or
      no evidence of degradation over the past century. However, the available evidence
      suggests that coral diseases and the crown-of-thorns starfish will proliferate in
      such waters and hence the mandated eutrophication Trigger values for Chl a (~0.4
      0.45 mg m-3) will need to be decreased to ~0.2 mg m-3 for sustaining coral reef
      communities.

PMID- 24114071
TI  - An interactive governance and fish chain approach to fisheries rebuilding: a case
      study of the Northern Gulf cod in eastern Canada.
AB  - Rebuilding collapsed fisheries is a multifaceted problem, requiring a holistic
      governance approach rather than technical management fixes. Using the Northern
      Gulf cod case study in eastern Canada, we illustrate how a "fish chain"
      framework, drawn from the interactive governance perspective, is particularly
      helpful in analyzing rebuilding challenges. The analysis demonstrates that
      factors limiting rebuilding exist along the entire fish chain, i.e., the pre
      harvest, harvest, and post-harvest stages. These challenges are embedded in both
      the ecological and social systems associated with the Northern Gulf cod
      fisheries, as well as in the governing systems. A comparative analysis of the pre
      and post-collapse of the cod fisheries also reveals governance opportunities in
      rebuilding, which lie in policy interventions such as integrated and ecosystem
      based management, livelihood transitional programs, and cross-scale institutional
      arrangements. Lessons from the Northern Gulf cod case study, especially the
      missed opportunities to explore alternative governing options during the
      transition, are valuable for rebuilding other collapsed fisheries. 

PMID- 24114072
TI  - Nodal promotes the generation of M2-like macrophages and downregulates the
      expression of IL-12.
AB  - Nodal, a member of the TGF-beta superfamily, is an embryonic morphogen that is
      upregulated in different types of tumors. Nodal increases the tumorigenesis by
      inducing angiogenesis and promoting metastasis. Importantly, Nodal inhibition
      suppresses the growth and invasion of tumor. Since tumor-associated macrophages
      (TAMs) are the major infiltrating leukocytes in most cancers, we investigated
      whether Nodal is involved in the differentiation of TAMs. Our results revealed
      that Nodal inhibition in tumor microenvironment upregulated the production of IL
      12 in macrophages and reversed TAMs to classically activated macrophage
      phenotype. In contrast, treatment with recombinant Nodal (rNodal) decreased the
      expression of IL-12 in murine macrophages. Furthermore, rNodal promoted
      macrophage polarization to an alternatively activated macrophage-like/TAM
      phenotype and modulated its function. These results suggest that Nodal may play
      an important role in macrophage polarization and downregulation of IL-12. The
      rescued antitumor function of TAMs via the inhibition of Nodal expression could
      be a new therapeutic strategy for cancer treatment. 

PMID- 24114073
TI  - Electrical source imaging of sleep spindles.
AB  - To identify and compare cortical source generators of slow and fast sleep
      spindles in healthy subjects, electroencephalographic (EEG) signals were obtained
      from 256 channels, and sources on neuroanatomical Montreal Neurological Institute
      (MNI) space estimated with low-resolution brain electromagnetic tomography
      analysis (LORETA). Spindle activity was recorded in 18 healthy volunteers during
      daytime napping. Because of lack of sleep or excessive artifacts, data from 13
      subjects were analyzed off-line. Spindles were visually scored, marked, and
      bandpass filtered (slow 10-12 Hz or fast 12-14 Hz). EEG was segmented on the
      marker, and segments separately averaged. LORETA projected cortical sources on
      the MNI brain. Maximal intra- and inter-individual intensities were compared
      using the Wilcoxon test (P < .05) and cortical sources distribution compared
      using a chi2 test. Two to three slow spindles generators were consistently
      identified in frontal lobes, with additional sources in parietal and limbic lobes
      in half cases. Fast spindles had multiple temporo-parietal sources, with an
      inconstant frontal source. Inter-individual (P = 0.44), and intra-individual (P =
      0.09 slow and P = 0.10 fast spindles) source intensities were comparable. Slow
      spindles sources were preferentially concentrated over frontal cortices in
      comparison with fast spindles (P = 0.0009). Our results demonstrate multiple,
      synchronous, and equipotent spindles cortical generators in healthy subjects,
      with more anterior generators for slow spindles.

PMID- 24114074
TI  - A patient with progressive cognitive decline and periodic abnormal waves in EEG:
      PLEDs of neurosyphilis or PSDs of Creutzfeldt-Jakob disease?
AB  - We report one Chinese patient with neurosyphilis exhibiting periodic lateralized
      epileptiform discharges (PLEDs) in the electroencephalogram (EEG). The patient
      (male, 59 years old) manifested with progressive cognitive decline and abnormal
      behavior. After several days, he gradually lost contact with others, and fell
      into a coma. EEG revealed periodic abnormal waves, predominantly located in the
      right anterior frontal region. The serum and cerebrospinal fluid Venereal Disease
      Research Laboratory test and Treponema pallidum hemagglutination assay were
      positive. Magnetic resonance imaging (MRI) of brain showed focal atrophy in the
      right frontal and temporal region. Diffusion-weighted MRI showed "lace sign" in
      cortex, which could be seen as an early and special feature in Creutzfeldt-Jakob
      disease (CJD). To differentiate "PLEDs of neurosyphilis on EEG" from "periodic
      synchronous discharges (PSD) of CJD on EEG," we treated this patient with
      diazepam 20 mg intravenously. After 10 minutes, periodic abnormal waves on EEG
      disappeared, with improved mental status, which confirmed the diagnosis of PLEDs
      of neurosyphilis. Then, after the treatment with penicillin, the patient improved
      and returned to work.

PMID- 24114075
TI  - Prognostic value of chronic hepatitis B virus infection in patients with
      nasopharyngeal carcinoma: analysis of 1301 patients from an endemic area in
      China.
AB  - BACKGROUND: The current study investigated the prevalence and prognostic value of
      chronic hepatitis B virus (HBV) infection in patients with nasopharyngeal
      carcinoma (NPC) from an area in southern China in which HBV and NPC are endemic.
      METHODS: A total of 1301 patients with nonmetastatic, histologically proven NPC
      who were treated with radiotherapy or chemoradiotherapy were retrospectively
      reviewed. RESULTS: In this series, 142 of the 1301 patients (10.9%) had chronic
      HBV infection (hepatitis B surface antigen [HBsAg] seropositive). The percentages
      of non-cancer-related deaths (15.0% vs 12.1%; P = .618) and severe hepatic
      adverse events (3.5% vs 0.9%; P = .145) were similar among patients with NPC with
      and without HBV infection. The 5-year overall survival (OS), progression-free
      survival (PFS), and locoregional recurrence-free survival (LRFS) rates for
      patients with NPC with or without HBV infection were 70.9% and 80.8% (P = .003),
      63.7% and 73.0% (P = .016), and 81.7% and 88.2% (P = .035), respectively.
      Multivariate analysis identified chronic HBV infection in patients with NPC as an
      independent unfavorable prognostic factor for OS (hazards ratio [HR], 1.684; P =
      .003), PFS (HR, 1.451; P = .015), and LRFS (HR, 1.573; P = .048). Further
      analysis revealed that chronic HBV infection was an unfavorable, independent
      prognostic factor in patients with locoregionally advanced NPC, but not those
      with early-stage disease. In patients with stage III/IV NPC, HBsAg-positive
      patients had poorer OS (64.0% vs 77.2%; P = .003), PFS (56.2% vs 70.6%; P =
      .004), and LRFS (76.2% vs 88.3%; P = .002) compared with HBsAg-negative patients.
      On multivariate analysis, chronic HBV infection was found to be an independent
      adverse prognostic predictor for OS (HR, 1.734; P = .004), PFS (HR, 1.644; P =
      .003), and LRFS (HR, 2.108; P = .003) in patients with stage III/IV NPC.
      CONCLUSIONS: Chronic HBV infection is an independent adverse prognostic factor in
      patients with locoregionally advanced NPC.

PMID- 24114076
TI  - Emergence of the white-collar sign after coil embolization of cerebral aneurysms.
AB  - BACKGROUND: The white-collar sign (WCS) is represented by the formation of
      neointimal tissue at the level of the aneurysm neck as the successful outcome on
      follow-up angiography after coil embolization. WCS has been reported only in
      aneurysms treated with Matrix(r) coils. This is the first study to report WCS
      emergence in aneurysms treated with bare platinum coils, and potential factors
      associated with WCS emergence were evaluated. METHOD: Total 130 unruptured
      (female: male ratio, 100: 30; mean age, 60 years) cerebral aneurysms were treated
      with coil embolization. Embolization status was assessed immediately and 1 year
      after treatment, and emergence of WCS in follow-up angiography was assessed. We
      evaluated the association between WCS emergence and aneurysm location, dome
      diameter, neck diameter, dome-neck ratio, and type of coil used (bare platinum or
      bioactive). RESULTS: WCS appeared in nine aneurysms (6.9%), of which six were
      treated only with bare platinum coils. Neck diameter was significantly smaller in
      the WCS-positive group than in the WCS-negative group. The proportion of
      aneurysms treated with bioactive coils was not significantly different between
      the groups. Immediate embolization status in the WCS-positive group tended to be
      slightly better than that in the WCS-negative group. No aneurysmal morphological
      characteristics other than small neck diameter were associated with WCS
      emergence. CONCLUSIONS: WCS is not specific to bioactive coil usage. Small neck
      diameter was significantly associated with WCS emergence in our series. Further
      investigations to clarify the predictors of WCS will contribute to progress of
      aneurysmal embolization.

PMID- 24114077
TI  - Long-term outcome of the Cloward procedure for single-level cervical degenerative
      spondylosis. Clinical and radiological assessment after a 22-year mean follow-up.
AB  - PURPOSE: To evaluate the long-term outcomes of the classical Cloward procedure in
      single-level cervical spondylosis. METHODS: A retrospective study of 28 patients
      who were affected by cervical degenerative spondylosis at C4-C7 segments and
      treated by the Cloward technique at a single level from 1985-1995 was conducted.
      The average follow-up period was 22 years (range, 17-27 years). Preoperative
      clinical complaints were recorded and compared to the current clinical status.
      Preoperative, 3-6 months postoperative and a current radiographic study were
      analysed by evaluating the segmental and global sagittal alignment of the
      cervical spine as well as the occurrence of adjacent disc degeneration. RESULTS:
      The most frequently operated segment was C5-C6 (57.1 %), followed by C6-C7 (32.1
      %) and C4-C5 (7.1 %). Pain relief and symptom recovery experienced 3-6 months
      following the surgery was maintained at the most recent follow-up in 85 % of
      patients. Adjacent disc degeneration was detected in a total of 17 cases (60.7
      %). Overall, a group of 14 cases (50 %) had increased lordosis at C2-C7 at the
      most recent follow-up, with a mean gain of 1.5o Cobb. According to Odom's
      criteria, 17 patients (60.8 %) presented with excellent clinical outcome, 6 (21.4
      %) presented with good outcome, 5 had a (17.8 %) fair outcome, and none had a
      poor outcome. CONCLUSIONS: The Cloward technique provided excellent long-term
      clinical outcome in the treatment of single-level cervical degenerative
      spondylosis. There were no major alterations of the cervical sagittal balance,
      and the development of adjacent segment disease (ASD) was not specifically
      associated with the previous surgery.

PMID- 24114078
TI  - Free-standing Ag/C coaxial hybrid electrodes as anodes for Li-ion batteries.
AB  - Free-standing coaxially structured Ag/carbon hybrid electrodes were prepared as
      potential anodes for micro-Li-ion batteries, which show excellent electrochemical
      performance, being essentially due to the beneficial effect of the unique
      structure, i.e. the Ag-core enhances the flexibility and electrochemical
      kinetics, while the carbon shell buffers volumetric change during cycling. 

PMID- 24114079
TI  - End-tidal versus manually-controlled low-flow anaesthesia.
AB  - During low-flow manually-controlled anaesthesia (MCA) the anaesthetist needs
      constantly adjust end-tidal oxygen (EtO2) and anaesthetic concentrations (EtAA)
      to assure an adequate and safe anaesthesia. Recently introduced anaesthetic
      machines can automatically maintain those variables at target values, avoiding
      the burden on the anaesthetist. End-tidal-controlled anaesthesia (EtCA) and MCA
      provided by the same anaesthetic machine under the same fresh gas flow were
      compared. Eighty patients were prospectively observed: in MCA group (n = 40)
      target end-tidal sevoflurane (1%) and EtO2 concentrations (>= 35%) were manually
      controlled by the anaesthetist. In EtCA group (n = 40) the same anaesthetic
      machine with an additional end-tidal control feature was used to reach the same
      targets, rendering automatic the achievement and maintenance of those targets.
      Anaesthetic machine characteristics, amount of consumed gases, oxygen and
      sevoflurane efficiencies, and the amount of interventions by the anaesthetist
      were recorded. In EtCA group EtAA was achieved later (145 s) than in MCA (71 s)
      and remained controlled thereafter. Even though the target expired gas fractions
      were achieved faster in MCA, manual adjustments were required throughout
      anaesthesia for both oxygen and sevoflurane. In MCA patients the number of manual
      adjustments to stabilize EtAA and EtO2 were 137 and 107, respectively; no
      adjustment was required in EtCA. Low-flow anaesthesia delivered with an
      anaesthetic machine able to automatically control EtAA and EtO2 provided the same
      clinical stability and avoided the continuous manual adjustment of delivered
      sevoflurane and oxygen concentrations. Hence, the anaesthetist could dedicate
      more time to the patient and operating room activities.

PMID- 24114081
TI  - Thirty years of research on the functional analysis of problem behavior.
AB  - Hanley, Iwata, and McCord (2003) reviewed studies published through 2000 on the
      functional analysis (FA) of problem behavior. We update that review for 2001
      through 2012, including 158 more recent studies that reported data from 445 FAs.
      Combined with data obtained from Hanley et al., 435 FA studies, with line graphs
      for 981 FAs, have been published since 1961. We comment on recent trends in FA
      research and introduce the studies in the 2013 special issue of the Journal of
      Applied Behavior Analysis. 

PMID- 24114080
TI  - Epidemiology of pulmonary arterial hypertension.
AB  - The epidemiology of pulmonary arterial hypertension (PAH) has changed over the
      last decade. Remarkable advances in understanding the pathobiology and clinical
      care required in PAH have resulted in improved quality of life and survival.
      Despite such important progress, the long-term rate of survival is still
      unacceptable. The epidemiology of PAH could not be easily generalized globally,
      due to the fact that nearly all of the present data has been gathered from
      Western, multicenter, prospective registries. There are potentially marked
      differences in PAH patients from Western and Eastern populations, and from
      developed and developing countries. Therefore, it is clear that more registry
      data will be needed to address novel questions emerging with improved knowledge
      of PAH. 

PMID- 24114082
TI  - Effects of fixed versus random condition sequencing during multielement
      functional analyses.
AB  - It has been suggested that a fixed condition sequence might facilitate
      differential responding during multielement functional analyses (FAs) by
      capitalizing on or limiting sequence effects (Iwata, Pace, et al., 1994);
      however, the effects of condition sequence have not been examined empirically. We
      conducted fixed- and random-sequence FAs for 7 individuals with developmental
      disabilities to determine the relative effects that sequence may have on
      assessment outcomes. Experimental conditions during the fixed sequence were
      conducted in the following order: ignore, attention, play, and demand; condition
      order during the random sequence was determined randomly. Results showed that
      sequence had no influence on the FA outcomes for 3 subjects, whereas differential
      responding emerged either faster (1 subject) or only (3 subjects) under the fixed
      sequence for the remaining subjects. These results suggest that the fixed
      sequence, a simple modification, should be used when conducting multielement FAs
      to accommodate the influence of establishing operations across assessment
      conditions. 

PMID- 24114083
TI  - Conducting functional analyses of problem behavior via telehealth.
AB  - Behavior consultants conducted functional analyses (FAs) via telehealth with 20
      young children with autism spectrum disorders between the ages of 29 and 80
      months who displayed problem behavior and lived an average of 222 miles from the
      tertiary hospital that housed the behavior consultants. Participants' parents
      conducted all procedures during weekly telehealth consultations in regional
      clinics located an average of 15 miles from the participants' homes. Behavior
      consultants briefly trained parent assistants to provide on-site support for
      families during consultations. FAs completed within a multielement design
      identified environmental variables that maintained problem behavior for 18 of the
      20 cases, and interrater agreement averaged over 90%. Results suggested that
      behavior analysts can conduct FAs effectively and efficiently via telehealth. 

PMID- 24114084
TI  - Functional analysis screening for problem behavior maintained by automatic
      reinforcement.
AB  - A common finding in previous research is that problem behavior maintained by
      automatic reinforcement continues to occur in the alone condition of a functional
      analysis (FA), whereas behavior maintained by social reinforcement typically is
      extinguished. Thus, the alone condition may represent an efficient screening
      procedure when maintenance by automatic reinforcement is suspected. We conducted
      a series of 5-min alone (or no-interaction) probes for 30 cases of problem
      behavior and compared initial predictions of maintenance or extinction to
      outcomes obtained in subsequent FAs. Results indicated that data from the
      screening procedure accurately predicted that problem behavior was maintained by
      automatic reinforcement in 21 of 22 cases and by social reinforcement in 7 of 8
      cases. Thus, results of the screening accurately predicted the function of
      problem behavior (social vs. automatic reinforcement) in 28 of 30 cases. 

PMID- 24114085
TI  - Test-specific control conditions for functional analyses.
AB  - Most functional analyses of problem behavior include a common condition (play or
      noncontingent reinforcement) as a control for both positive and negative
      reinforcement. However, test-specific conditions that control for each potential
      source of reinforcement may be beneficial occasionally. We compared responding
      during alone, ignore, play, and differential reinforcement of other behavior
      (DRO) control conditions for individuals whose problem behavior was maintained by
      positive or negative reinforcement. Results showed that all of the conditions
      were effective controls for problem behavior maintained by positive
      reinforcement; however, the DRO condition was consistently ineffective as a
      control for problem behavior maintained by negative reinforcement. Implications
      for the design of functional analyses and future research are discussed. 

PMID- 24114086
TI  - Evaluation of the divided attention condition during functional analyses.
AB  - A common condition included in most functional analyses (FAs) is the attention
      condition, in which the therapist ignores the client by engaging in a solitary
      activity (antecedent event) but delivers attention to the client contingent on
      problem behavior (consequent event). The divided attention condition is similar,
      except that the antecedent event consists of the therapist conversing with an
      adult confederate. We compared the typical and divided attention conditions to
      determine whether behavior in general (Study 1) and problem behavior in
      particular (Study 2) were more sensitive to one of the test conditions. Results
      showed that the divided attention condition resulted in faster acquisition or
      more efficient FA results for 2 of 9 subjects, suggesting that the divided
      attention condition could be considered a preferred condition when resources are
      available. 

PMID- 24114087
TI  - Therapist and setting influences on functional analysis outcomes.
AB  - Functional analyses (FAs) of problem behavior typically are conducted in
      controlled settings to minimize potential sources of confounding. Several studies
      have reported that results of FAs conducted in controlled settings occasionally
      differ from those conducted under more naturalistic conditions, although little
      is known about factors that may contribute to the different outcomes. We examined
      correspondence between FAs conducted by staff in a clinic and those conducted
      either by caregivers as therapists or in the home setting. If results of the 2
      analyses were dissimilar, we conducted further analyses to identify variables
      responsible for the different outcomes. Results showed that, in most cases,
      correspondence of function was observed across familiar and unfamiliar stimuli.
      Results are discussed in terms of implications for research and clinical practice
      for the evaluation of problem behavior. 

PMID- 24114088
TI  - Initial functional analysis outcomes and modifications in pursuit of
      differentiation: a summary of 176 inpatient cases.
AB  - The functional analysis (FA) described by Iwata, Dorsey, Slifer, Bauman, and
      Richman (1982/1994) delineated not only a set a specific procedures, but also a
      model that involves the use of analogue conditions wherein antecedent and
      consequent variables are systematically manipulated. This consecutive case-series
      analysis describes FAs of 176 individuals with intellectual disabilities who had
      been admitted to an inpatient unit for severe problem behavior. Following an
      initial standardized FA, additional modifications were performed in pursuit of
      differentiation. Ultimately, a function was identified in 86.9% of the 176 cases
      and in 93.3% of the 161 cases for which the FA, if necessary, was modified up to
      2 times. All modifications were documented and classified as involving changes to
      antecedents, consequences, or design (or some combination of these). Outcomes for
      each type of modification are reported. The results support the utility of
      ongoing hypothesis testing through individualized modifications to FA procedures,
      and provide information regarding how each type of modification affected results.

PMID- 24114089
TI  - Experimental analysis of precursors to severe problem behavior.
AB  - Some individuals engage in both mild and severe forms of problem behavior.
      Research has shown that when mild behaviors precede severe behaviors (i.e., the
      mild behaviors serve as precursors), they can (a) be maintained by the same
      source of reinforcement as severe behavior and (b) reduce rates of severe
      behavior observed during assessment. In Study 1, we developed an objective
      checklist to identify precursors via videotaped trials for 16 subjects who
      engaged in problem behavior and identified at least 1 precursor for every
      subject. In Study 2, we conducted separate functional analyses of precursor and
      severe problem behaviors for 8 subjects, and obtained correspondence between
      outcomes in 7 cases. In Study 3, we evaluated noncontingent reinforcement
      schedule thinning plus differential reinforcement of alternative behavior to
      reduce precursors, increase appropriate behavior, and maintain low rates of
      severe behavior during 3 treatment analyses for 2 subjects. Results showed that
      this treatment strategy was effective for behaviors maintained by positive and
      negative reinforcement. 

PMID- 24114090
TI  - Using modified visual-inspection criteria to interpret functional analysis
      outcomes.
AB  - The development of functional analysis (FA) methodologies allows the
      identification of the reinforcers that maintain problem behavior and improved
      intervention efficacy in the form of function-based treatments. Despite the
      profound impact of FA on clinical practice and research, questions still remain
      about the methods by which clinicians and researchers interpret FA graphs. In the
      current study, 141 FA data sets were evaluated using the structured visual
      inspection criteria developed by Hagopian et al. (1997). However, the criteria
      were modified for FAs of varying lengths. Interobserver agreement assessments
      revealed high agreement coefficients across expert judges, postdoctoral
      reviewers, master's-level reviewers, and postbaccalaureate reviewers. Once the
      validity of the modified visual-inspection procedures was established, the
      utility of those procedures was examined by using them to categorize the
      maintaining reinforcement contingency related to problem behavior for all 141
      data sets and for the 101 participants who contributed to the 141 data sets. 

PMID- 24114091
TI  - Assessment and treatment of social avoidance.
AB  - Problem behavior maintained by social-negative reinforcement often is evoked by a
      specific type of social interaction--the presentation of task demands. This study
      involved assessment and treatment of a more general form of social avoidance in
      which the establishing operation (EO) for problem behavior consisted of social
      interaction per se. Four subjects exhibited high rates of problem behavior during
      the play or demand conditions of a functional analysis (FA). A subsequent FA in
      which problem behavior produced escape from social interaction confirmed social
      avoidance for all subjects. A series of interventions aimed at attenuating
      aversive characteristics of social interaction then was implemented with 3 of the
      subjects. These interventions included vicarious reinforcement, conditioning of
      social interaction as a reinforcer, stimulus fading, and differential
      reinforcement (DRA) plus extinction (EXT). DRA plus EXT was the only condition in
      which decreases in problem behavior and increases in social interactions were
      observed reliably.

PMID- 24114092
TI  - An individualized and comprehensive approach to treating sleep problems in young
      children.
AB  - We evaluated the effects of assessment-based interventions on the treatment of
      sleep problems in 3 young children, 2 of whom had been diagnosed with autism. We
      used sleep diaries and infrared nighttime video in the child's bedroom to obtain
      measures of sleep onset, sleep-interfering behaviors, night waking, total sleep,
      parental presence, and medication administration each night. We then identified
      environmental factors that contributed to sleep problems using an open-ended
      interview called the Sleep Assessment and Treatment Tool. Individualized
      treatment packages were designed with the children's parents based on the
      idiosyncratic results of the assessment. Treatment packages included adjustment
      of the sleep schedule based on developmental norms and current sleep phases,
      design of a sleep-conducive environment, elimination of inappropriate sleep
      dependencies, and function-based interventions to decrease sleep-interfering
      behaviors by disrupting the contingency between the interfering behavior and its
      likely reinforcement. A nonconcurrent multiple baseline design across subjects
      revealed that treatment was effective for all 3 children. In addition, social
      acceptability measures showed that the parents were satisfied with the assessment
      process, the treatment, and the amount of behavior change. 

PMID- 24114093
TI  - Assessment and treatment of chronic hand mouthing.
AB  - Hand mouthing (HM) is a chronic problem in many individuals with intellectual
      disabilities. Although the prevalence of mouthing has been estimated, data on the
      frequency, severity, or functions of the behavior were not included. In Study 1,
      we examined the prevalence and risk of HM. Results obtained from interviews
      showed that the prevalence of HM in two institutional samples (N = 802) was
      12.7%, whereas direct observation yielded a lower estimate of prevalence (8%).
      Moreover, a large proportion of observed HM (39.1%) was self-injurious in nature.
      In Study 2, we used modified functional analyses (FAs) to examine the HM of 64
      individuals. Results indicated that maintenance by automatic reinforcement
      accounted for 98.4% of the cases (all but one case). In Study 3, we implemented a
      progressive series of interventions for HM exhibited by 14 individuals. The
      following interventions were implemented in sequential order: (a) noncontingent
      reinforcement (NCR, effective with 6 subjects), (b) either NCR plus differential
      reinforcement of alternative behavior (DRA) plus response blocking (effective
      with 5 subjects) or NCR plus response blocking only (effective with 2 subjects),
      and (c) NCR plus brief manual restraint (effective with 1 subject).

PMID- 24114094
TI  - A functional analysis of moderate-to-vigorous physical activity in young
      children.
AB  - Inadequate physical activity increases the risks related to a number of health
      problems in children, most notably obesity and the corresponding range of
      associated health problems. The purpose of the current study was to conduct a
      functional analysis to investigate the effects of several consequent variables on
      moderate-to-vigorous physical activity (MVPA). We observed the level of MVPA
      exhibited by 2 preschool children in 4 conditions: alone, attention contingent on
      MVPA, adult interaction contingent on MVPA, and escape from task demands
      contingent on MVPA. These four conditions were compared to a naturalistic
      baseline and to a control condition. Overall, results indicated that the children
      were most active when attention and interactive play were contingent on MVPA.
      Social environments that encourage MVPA could be arranged based on this
      information, with these arrangements tailored to the individual child. 

PMID- 24114095
TI  - Teacher-conducted trial-based functional analyses as the basis for intervention.
AB  - Previous studies have focused on whether a trial-based functional analysis (FA)
      yields the same outcomes as more traditional FAs, and whether interventions based
      on trial-based FAs can reduce socially maintained problem behavior. We included a
      full range of behavior functions and taught 3 teachers to conduct a trial-based
      FA with 3 boys with developmental and intellectual disabilities who engaged in
      problem behavior. Based on the results of the trial-based FAs, we developed and
      conducted 5 function-based interventions, using differential reinforcement of an
      alternative behavior and extinction in all but 1 case. In the remaining case, we
      used noncontingent reinforcement. All interventions led to reductions in problem
      behavior and increases in alternative behavior. 

PMID- 24114096
TI  - A component analysis of schedule thinning during functional communication
      training.
AB  - One limitation of functional communication training (FCT) is that individuals may
      request reinforcement via the functional communication response (FCR) at
      exceedingly high rates. Multiple schedules with alternating periods of
      reinforcement and extinction of the FCR combined with gradually lengthening the
      extinction-component interval can effectively address this limitation. However,
      the extent to which each of these components contributes to the effectiveness of
      the overall approach remains uncertain. In the current investigation, we
      evaluated the first component by comparing rates of the FCR and problem behavior
      under mixed and multiple schedules and evaluated the second component by rapidly
      switching from dense mixed and multiple schedules to lean multiple schedules
      without gradually thinning the density of reinforcement. Results indicated that
      multiple schedules decreased the overall rate of reinforcement for the FCR and
      maintained the strength of the FCR and low rates of problem behavior without
      gradually thinning the reinforcement schedule. 

PMID- 24114098
TI  - A simplified methodology for identifying the function of elopement.
AB  - Functional analyses of elopement (i.e., leaving a specific area without
      permission) are challenging to conduct because clients must have repeated
      opportunities to elope from one room (or area) to another safely. These analyses
      often require two or more adjoining rooms and retrieval of the client following
      each instance of elopement (e.g., Piazza et al., 1997). These room arrangements
      may be impractical in some settings, and therapist delivery of attention or
      demands during retrieval may confound the results. To address these issues, we
      evaluated the viability of conducting a functional analysis (FA) of elopement
      within a single room. Participants were 2 children and 2 adults with
      developmental disabilities who eloped from rooms at their day programs. Results
      of the single-room assessments were compared to those of a second FA that was
      conducted using methods similar to those described in previous studies. Function
      based treatments were implemented for each participant. Results suggest that the
      single-room assessment may be a viable alternative for identifying the function
      of elopement. 

PMID- 24114097
TI  - Does supplementary reinforcement of stereotypy facilitate extinction?
AB  - Results of several studies suggest that delivery of supplemental (social)
      reinforcement for stereotypy might facilitate its subsequent extinction. We
      examined this possibility with 9 subjects who engaged in stereotypy by including
      methodological refinements to ensure that (a) subjects' stereotypy was maintained
      in the absence of social consequences, (b) supplementary reinforcers were highly
      preferred and were shown to be reinforcers for some behavior, and (c) subjects
      were exposed to lengthy reinforcement and extinction conditions. In spite of
      these modifications, only 4 subjects' stereotypy increased when supplementary
      reinforcement was delivered contingent on stereotypy, and no subject's stereotypy
      decreased below initial baseline levels when social reinforcement was
      subsequently withheld. Decreases in stereotypy occurred with the implementation
      of noncontingent reinforcement. Thus, delivery of supplementary reinforcers
      either did not increase stereotypy or did not facilitate extinction of stereotypy
      maintained by automatic reinforcement. We discuss the practical and conceptual
      bases of these results with respect to our current understanding of function
      based interventions. 

PMID- 24114099
TI  - Reliability and validity of the functional analysis screening tool.
AB  - The Functional Analysis Screening Tool (FAST) is a 16-item questionnaire about
      antecedent and consequent events that might be correlated with the occurrence of
      problem behavior. Items are organized into 4 functional categories based on
      contingencies that maintain problem behavior. We assessed interrater reliability
      of the FAST with 196 problem behaviors through independent administration to
      pairs of raters (Study 1). Mean item-by-item agreement between pairs of raters
      was 71.5%. Agreement for individual items ranged from 53.3% to 84.5%. Agreement
      on FAST outcomes, based on comparison of informants' highest totals, was 64.8%.
      We assessed the validity of the FAST by comparing its outcomes with results of 69
      functional analyses (Study 2). The FAST score predicted the condition of the
      functional analysis in which the highest rate of problem behavior occurred in 44
      cases (63.8%). Potential uses of the FAST in the context of a clinical interview,
      as well as limitations, are discussed. 

PMID- 24114100
TI  - On the origin and functions of the term functional analysis.
AB  - In this essay, we note that although Iwata, Dorsey, Slifer, Bauman, and Richman
      (1982) established the standard framework for conducting functional analyses of
      problem behavior, the term functional analysis was probably first used in
      behavior analysis by B. F. Skinner in 1948. We also remind readers that a
      functional analysis is really an experimental analysis, words that were contained
      in the title of Skinner's first book, The Behavior of Organisms: An Experimental
      Analysis (1938). We further describe how Skinner initially applied the concept of
      functional analysis to an understanding of verbal behavior, and we suggest that
      the same tactic be applied to the verbal behavior of behavior analysts, in the
      present case, to the term functional analysis. 

PMID- 24114101
TI  - Functional analysis and treatment of problem behavior in early education
      classrooms.
AB  - We conducted functional analyses (FA) with 4 typically developing preschool
      children during ongoing classroom activities and evaluated treatments that were
      based on FA results. Results of each child's FA suggested social-positive
      reinforcement functions, and differential reinforcement of alternative behavior
      plus time-out was effective in decreasing problem behavior and increasing
      appropriate behavior. We discuss the utility of classroom-based FAs and potential
      compromises to experimental control. 

PMID- 24114102
TI  - Training residential staff to conduct trial-based functional analyses.
AB  - We taught 6 supervisors of a residential service provider for adults with
      developmental disabilities to train 9 house managers to conduct trial-based
      functional analyses. Effects of the training were evaluated with a nonconcurrent
      multiple baseline. Results suggest that house managers can be trained to conduct
      trial-based functional analyses with a high degree of procedural fidelity. 

PMID- 24114103
TI  - Evaluation of the utility of a discrete-trial functional analysis in early
      intervention classrooms.
AB  - We evaluated a discrete-trial functional analysis implemented by regular
      classroom staff in a classroom setting. The results suggest that the discrete
      trial functional analysis identified a social function for each participant and
      may require fewer staff than standard functional analysis procedures. 

PMID- 24114104
TI  - Functional assessment and treatment of perseverative speech about restricted
      topics in an adolescent with Asperger syndrome.
AB  - A functional analysis showed that a 14-year-old boy with Asperger syndrome
      displayed perseverative speech (or "restricted interests") reinforced by
      attention. To promote appropriate speech in a turn-taking format, we implemented
      differential reinforcement (DR) of nonperseverative speech and DR of on-topic
      speech within a multiple schedule with stimuli that signaled the contingencies in
      effect and who was to select the topic. Both treatments reduced perseverative
      speech, but only DR of on-topic speech increased appropriate turn taking during
      conversation. Treatment effects were maintained when implemented by family
      members and novel therapists. 

PMID- 24114105
TI  - Latency of response during the functional analysis of elopement.
AB  - Elopement is a dangerous behavior sometimes exhibited by individuals with
      intellectual disabilities. We conducted trial-based functional analyses in which
      latency was the index of elopement for 2 students. Two unobtrusive safety
      monitors were placed outside the building to eliminate potential confounding
      caused by having to retrieve a student. Results of both students' assessments
      indicated that elopement served multiple functions. Results are discussed in
      terms of the study's methodological and applied implications. 

PMID- 24114106
TI  - A functional analysis of crying.
AB  - Crying has yet to be examined systematically in isolation from other problem
      behavior, such as aggression or tantrums, during functional analyses (Hanley,
      Iwata, & McCord, 2003). Identification of variables that may maintain crying is
      especially important for populations who are susceptible to psychiatric
      interventions (e.g., individuals who have intellectual disabilities and
      communication deficits). The current study extended functional analysis
      methodology to crying with an adolescent boy who had been diagnosed with
      intellectual disabilities. Results suggested that crying was maintained by
      caregiver attention delivered in a sympathetic manner. 

PMID- 24114107
TI  - Functional analysis and treatment of diurnal bruxism.
AB  - An analogue functional analysis identified attention as a function for a 5-year
      old boy's bruxism (teeth grinding). Functional communication training resulted in
      a reduction of bruxism and an increase in alternative mands for attention.
      Results were maintained 3 weeks following the intervention. 

PMID- 24114108
TI  - Functional analysis and intervention for chronic rumination.
AB  - We conducted a functional analysis and treatment evaluation of chronic rumination
      in a 19-year-old man with intellectual disabilities. Outcomes of the functional
      analysis suggested that rumination was maintained by automatic reinforcement.
      Results of the intervention evaluation suggested that (a) noncontingent access to
      food after meals reduced rumination more effectively than did noncontingent
      access to inedible stimuli, (b) a particular type of food was associated with
      lower levels of rumination than other types of food, and (c) both presession and
      continuous access to food reduced levels of rumination more effectively than did
      fixed-time access to food. 

PMID- 24114109
TI  - Persistence during extinction: examining the effects of continuous and
      intermittent reinforcement on problem behavior.
AB  - This study examined behavioral persistence during extinction following continuous
      or intermittent reinforcement in the context of an analogue functional analysis
      of problem behavior. Participants were 4 children who had been diagnosed with an
      autism spectrum disorder and who engaged in problem behavior maintained by social
      reinforcement. Experimental sessions included 4 successive 5-min components: no
      social interaction, continuous or intermittent reinforcement for problem behavior
      (alternating across sessions), extinction, and no social interaction. All
      participants' problem behavior was more persistent during extinction following
      continuous reinforcement, suggesting that behavior during extinction was affected
      by the preceding schedule of reinforcement. 

PMID- 24114111
TI  - Functional analysis of verbal behavior: a brief review.
AB  - A variation of the preintervention functional analysis of problem behavior has
      recently been extended to identify the function of verbal behavior emitted by
      children with autism. Recent research suggests that a functional analysis of
      verbal behavior might be beneficial in evaluating previous instruction and
      guiding the selection of future educational targets and instructional procedures.
      The present paper reviews previous literature on the functional analysis of
      verbal behavior and identifies avenues for future research. 

PMID- 24114110
TI  - Idiosyncratic variables that affect functional analysis outcomes: a review (2001
      2010).
AB  - Although typical functional analyses often produce clear outcomes, some studies
      have reported ambiguous results that cannot be interpreted. Such undifferentiated
      outcomes may occur if test conditions do not include relevant antecedent or
      consequent events. Clinicians then may try to modify the functional analysis
      conditions to include those events. Hanley, Iwata, and McCord (2003) reviewed the
      functional analysis literature through 2000 and described idiosyncratic variables
      included in modified functional analyses. The objective of the present review was
      to present a quantitative analysis of idiosyncratic antecedents and consequences
      in modified functional analyses during the past decade (2001 to 2010). We discuss
      the range of stimulus parameters tested and the assessment strategies used for
      informing the modified analysis conditions. 

PMID- 24114112
TI  - A measure for characterizing sliding on lung boundaries.
AB  - The lobes of the lung slide relative to each other during breathing. Quantifying
      lobar sliding can aid in better understanding lung function, better modeling of
      lung dynamics, and for studying phenomenon such as pleural adhesion. We propose a
      novel measure to characterize lobe sliding in the lung based on the displacement
      field obtained from image registration of CT scans. When two sliding lobes are
      modeled as a continuum, the discontinuity in the displacement field at the
      fissure will manifest as elevated maximum shear--the proposed measure--which is
      capable of capturing both the level and orientation of sliding. Six human lungs
      were analyzed using scans spanning functional residual capacity to total lung
      capacity. The lung lobes were segmented and registered on a lobe-by-lobe basis to
      obtain the displacement field from which the proposed sliding measure was
      calculated. The sliding measure was found to be insignificant in the parenchyma,
      as relatively little tissue shear occurs here. On the other hand, it was elevated
      along the fissures. Thus, a map of the proposed sliding measure of the entire
      lung clearly delineates and quantifies sliding between lung lobes. Sliding is a
      key aspect of lung deformation during breathing. The proposed measure may help
      resolve artifacts introduced by sliding in deformation analysis techniques used
      for radiotherapy.

PMID- 24114113
TI  - Immune cell-mediated inflammation and the early improvements in glucose
      metabolism after gastric banding surgery.
AB  - AIMS/HYPOTHESIS: The contribution of immune cells to the inflammasome that
      characterises type 2 diabetes mellitus and obesity is under intense research
      scrutiny. We hypothesised that early changes in glucose metabolism following
      gastric banding surgery may relate to systemic inflammation, particularly cell
      mediated immunity. METHODS: Obese participants (BMI 43.4 +/- 4.9 kg/m(2), n = 15)
      with diabetes or impaired glucose tolerance (IGT) underwent laparoscopic
      adjustable gastric banding surgery. Measurements taken before, and at 2 and 12
      weeks after surgery included: fasting glucose, glucose levels 2 h after a 75 g
      oral load, glucose incremental AUC, oral glucose insulin sensitivity index
      (OGIS), circulating immune cell numbers and activation, and adipokine levels.
      Subcutaneous and visceral adipose tissue were collected at surgery, and
      macrophage number and activation measured. RESULTS: There were significant
      reductions in fasting and 2 h glucose, as well as improved OGIS at 2 and 12
      weeks. At 12 weeks, 80% of the diabetic participants reverted to normal glucose
      tolerance or IGT, and all IGT participants had normalised glucose tolerance. The
      12 week fall in fasting glucose was significantly related to baseline lymphocyte
      and T lymphocyte numbers, and to granulocyte activation, but also to the
      magnitude of the 12 week reduction in lymphocyte and T lymphocyte numbers and TNF
      alpha levels. In a model that explained 75% of the variance in the change in
      fasting glucose, the 12 week change in T lymphocytes was independently associated
      with the 12 week fall in fasting glucose. CONCLUSIONS/INTERPRETATION: Rapid
      improvements in glucose metabolism after gastric banding surgery are related to
      reductions in circulating pro-inflammatory immune cells, specifically T
      lymphocytes. The contribution of immune cell-mediated inflammation to glucose
      homeostasis in type 2 diabetes and its improvement after bariatric surgery
      require further investigation.

PMID- 24114114
TI  - Mortality trends in patients with and without diabetes in Ontario, Canada and the
      UK from 1996 to 2009: a population-based study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate
      ratio of mortality and changes over time in individuals with vs without diabetes.
      METHODS: Annual age- and sex-adjusted mortality rates were compared for adults
      (>20 years) with and without diabetes in Ontario, Canada, and the UK from January
      1996 to December 2009 using The Health Improvement Network (THIN) and Ontario
      databases. The total number of individuals evaluated increased from 8,757,772 in
      1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals
      with diabetes in both cohorts was significantly lower during later vs earlier
      years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate
      ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in
      2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In
      Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were
      1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11
      (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively.
      Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64
      (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18
      (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess
      risk of mortality in individuals with vs without diabetes has decreased over time
      in both Canada and the UK. This may be in part due to earlier detection and
      higher prevalence of early diabetes, as well as to improvements in diabetes care.

PMID- 24114115
TI  - Glucose-stimulated insulin secretion: the hierarchy of its multiple cellular and
      subcellular mechanisms.
AB  - Glucose-stimulated insulin secretion is ensured by multiple molecular, cellular
      and tissue events. In this issue of Diabetologia, Low et al (DOI: 10.1007/s00125
      013-3019-5 ) have taken an important new step towards understanding the
      hierarchical organisation of these events, by monitoring in vitro the individual
      exocytosis of multiple beta cells within intact mouse islets. The authors show
      that glucose stimulation markedly increases the number of exocytotic events per
      cell and, to a lesser extent, the number of beta cells contributing to this
      event. In this commentary we discuss these novel observations and propose that
      metabolic and electrical coupling of islet beta cells is responsible for a more
      homogeneous glucose-induced secretory response of cells in an intact islet as
      compared with isolated beta cells. 

PMID- 24114116
TI  - Low temperature n-butyllithium-induced [3,3]-sigmatropic
      rearrangement/electrophile trapping reactions of allyl-1,1-dichlorovinyl ethers.
      Synthesis of beta-, gamma- and delta-lactones.
AB  - Treatment of allyl-1,1-dichlorovinyl ethers with n-BuLi at -78  degrees C,
      followed by quenching with ketones, epoxides, and oxetanes, leads to highly
      substituted beta-, gamma-, and delta-lactones in good to excellent yields. 

PMID- 24114117
TI  - Axial computed tomography pulmonary angiogram.

PMID- 24114118
TI  - Many states lagging in efforts to curb prescription drug misuse, says report.

PMID- 24114119
TI  - Structural adaptation of tooth enamel protein amelogenin in the presence of SDS
      micelles.
AB  - Amelogenin, the major extracellular matrix protein of developing tooth enamel is
      intrinsically disordered. Through its interaction with other proteins and
      mineral, amelogenin assists enamel biomineralization by controlling the formation
      of highly organized enamel crystal arrays. We used circular dichroism (CD),
      dynamic light scattering (DLS), fluorescence, and NMR spectroscopy to investigate
      the folding propensity of recombinant porcine amelogenin rP172 following its
      interaction with SDS, at levels above critical micelle concentration. The rP172
      SDS complex formation was confirmed by DLS, while an increase in the structure
      moiety of rP172 was noted through CD and fluorescence experiments. Fluorescence
      quenching analyses performed on several rP172 mutants where all but one Trp was
      replaced by Tyr at different sequence regions confirmed that the interaction of
      amelogenin with SDS micelles occurs via the N-terminal region close to Trp25
      where helical segments can be detected by NMR. NMR spectroscopy and structural
      refinement calculations using CS-Rosetta modeling confirm that the highly
      conserved N-terminal domain is prone to form helical structure when bound to SDS
      micelles. Our findings reported here reveal interactions leading to significant
      changes in the secondary structure of rP172 upon treatment with SDS. These
      interactions may reflect the physiological relevance of the flexible nature of
      amelogenin and its sequence specific helical propensity that might enable it to
      structurally adapt with charged and potential targets such as cell surface,
      mineral, and other proteins during enamel biomineralization.

PMID- 24114121
TI  - A phase I study of vorinostat in combination with bortezomib in patients with
      advanced malignancies.
AB  - BACKGROUND: A phase I study to assess the maximum-tolerated dose (MTD), dose
      limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of
      vorinostat in combination with bortezomib in patients with advanced solid tumors.
      METHODS: Patients received vorinostat orally once daily on days 1-14 and
      bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose
      (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing
      was increased using a standard phase I dose-escalation schema. PKs were evaluated
      during cycle 1. RESULTS: Twenty-three patients received 57 cycles of treatment on
      four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was
      established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted
      of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and
      grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2
      toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%),
      anorexia (30.4%) and constipation (26.1%). Objective partial responses were
      observed in one patient with NSCLC and in one patient with treatment-refractory
      soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however,
      the Cmax and AUC of the acid metabolite were significantly increased on day 2
      compared with day 1. CONCLUSIONS: This combination was generally well-tolerated
      at doses that achieved clinical benefit. The MTD was established at vorinostat
      400 mg daily * 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21
      day cycle.

PMID- 24114122
TI  - UGT1A1 genotype-guided phase I study of irinotecan, oxaliplatin, and
      capecitabine.
AB  - PURPOSE: We performed a UGT1A1 genotype-guided study to determine the maximum
      tolerated dose (MTD) and evaluate the toxicities and pharmacokinetics of the
      combination of capecitabine (CAP), oxaliplatin (OX), and irinotecan (IRIN).
      EXPERIMENTAL DESIGN: Patients were screened for UGT1A1 *28 genotype prior to
      treatment. The starting dose (mg/m(2)) was IRIN (150), OX (85) and CAP (400),
      days 2-15. Doses were escalated or de-escalated within each genotype group
      (*28/*28, *1/*28 and *1/*1). IRIN pharmacokinetics was performed at the MTD.
      RESULTS: 50 patients were evaluable for toxicity [11 (*28/*28); 18 (*1/*28); 21
      (*1/*1)]. UGT1A1 *28/*28 patients experienced hematologic dose limiting toxicity
      (DLT), requiring dose-de-escalation. The UGT1A1 *28/*28 recommended phase 2 dose
      (RP2D) was IRIN (75), OX (85), and CAP (400). In contrast, both UGT1A1 *1/*28 and
      *1/*1 tolerated higher doses of IRIN and non-hematologic toxicity was dose
      limiting for UGT1A1 *1/*1. The RP2D was IRIN (150), OX (85), and CAP (400) for
      UGT1A1*1/*28 and IRIN (150), OX (100), and CAP (1600) for UGT1A1 *1/*1. UGT1A1
      *1/*28 and *1/*1 patients treated with IRIN (150) had similar AUCs for the active
      irinotecan metabolite, SN38 (366 +/- 278 and 350 +/- 159 ng/ml*hr, respectively).
      UGT1A1 *28/*28 patients (n = 3) treated with a lower IRIN dose (100) had non
      significantly higher mean SN38 exposures (604 +/- 289 ng/ml*hr, p = 0.14).
      Antitumor activity was observed in all genotype groups. CONCLUSIONS: UGT1A1
      genotype affects the dose and pharmacokinetics of the CAPIRINOX regimen and
      UGT1A1 genotype-guided dosing of CAPIRINOX is ongoing in a phase II study of
      small bowel cancer (NCT00433550).

PMID- 24114123
TI  - A Phase I study of intermittently dosed vorinostat in combination with bortezomib
      in patients with advanced solid tumors.
AB  - BACKGROUND: Accumulating evidence shows evidence of efficacy with the combination
      of vorinostat and bortezomib in solid tumors. We previously examined a once-daily
      continuous dosing schedule of vorinostat in combination with bortezomib which was
      well tolerated in cycles 1 and 2; however, there was concern regarding the
      tolerability through multiple cycles. This study was conducted to evaluate an
      intermittent dosing schedule of vorinostat with bortezomib. METHODS: Vorinostat
      was initially administered orally twice daily on days 1-14 with bortezomib IV on
      days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were
      observed at dose level 1, thus the protocol was amended to administer vorinostat
      intermittently twice daily on days 1-4 and 8-11. RESULTS: 29 patients were
      enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic,
      colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose
      level included thrombocytopenia, fatigue, increased ALT, elevated INR, and
      diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and
      fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to
      those observed in the daily dosing. In this heavily pretreated population, stable
      disease was observed in patients with sarcoma, colorectal adenocarcinoma and
      GIST. CONCLUSIONS: The MTD was established at vorinostat 300 mg BID on days 1-4
      and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle.
      Tolerability was not improved with the intermittent dosing schedule of vorinostat
      when compared to continuous dosing.

PMID- 24114127
TI  - Entopic image of dislocated intraocular lens.

PMID- 24114124
TI  - Characterization and preclinical development of LY2603618: a selective and potent
      Chk1 inhibitor.
AB  - Interference with DNA damage checkpoints has been demonstrated preclinically to
      be a highly effective means of increasing the cytotoxicity of a number of DNA
      damaging cancer therapies. Cell cycle arrest at these checkpoints protects
      injured cells from apoptotic cell death until DNA damage can be repaired. In the
      absence of functioning DNA damage checkpoints, cells with damaged DNA may proceed
      into premature mitosis followed by cell death. A key protein kinase involved in
      activating and maintaining the S and G2/M checkpoints is Chk1. Pharmacological
      inhibition of Chk1 in the absence of p53 functionality leads to abrogation of DNA
      damage checkpoints and has been shown preclinically to enhance the activity of
      many standard of care chemotherapeutic agents. LY2603618 is a potent and
      selective small molecule inhibitor of Chk1 protein kinase activity in vitro
      (IC(50) = 7 nM) and the first selective Chk1 inhibitor to enter clinical cancer
      trials. Treatment of cells with LY2603618 produced a cellular phenotype similar
      to that reported for depletion of Chk1 by RNAi. Inhibition of intracellular Chk1
      by LY2603618 results in impaired DNA synthesis, elevated H2A.X phosphorylation
      indicative of DNA damage and premature entry into mitosis. When HeLa cells were
      exposed to doxorubicin to induce a G2/M checkpoint arrest, subsequent treatment
      with LY2603618 released the checkpoint, resulting in cells entering into
      metaphase with poorly condensed chromosomes. Consistent with abrogation of the
      Chk1 and p53-dependent G2/M checkpoint, mutant TP53 HT-29 colon cancer cells were
      more sensitive to gemcitabine when also treated with LY2603618, while wild-type
      TP53 HCT116 cells were not sensitized by LY2603618 to gemcitabine. Treatment of
      Calu-6 human mutant TP53 lung cancer cell xenografts with gemcitabine resulted in
      a stimulation of Chk1 kinase activity that was inhibited by co-administration of
      LY2603618. By all criteria, LY2603618 is a highly effective inhibitor of multiple
      aspects of Chk1 biology.

PMID- 24114128
TI  - Choroidal detachment due to hypotony after intravitreal injection of
      dexamethasone implant.

PMID- 24114131
TI  - Uveal coloboma.

PMID- 24114132
TI  - Intraocular and orbital hemorrhage in a patient with dengue fever during cataract
      surgery.

PMID- 24114133
TI  - Initial presentation of pseudoxanthoma elasticum.

PMID- 24114134
TI  - An eye chart for Edgar Degas.
AB  - The French Impressionist painter Edgar Degas had progressive visual loss from a
      type of maculopathy during the last 40 years of his life. The effects of this
      visual failure are evident in a comparison of early and later pastels, which
      shows a loss of precision in outlining, shading, and detail over the years. A
      remarkable oil painting, Scene from the Steeplechase: The Fallen Jockey, provides
      on one canvas an historical record of his visual struggles. It was begun in 1866
      and reworked in 1880 and 1897, during which his visual acuity fell from near
      normal to 20/200. Computer simulations show Degas' own view of this painting at
      each of these times and demonstrate how his style changed: details became rougher
      and larger in correspondence with his failing acuity. The painting is an eye
      chart of his career. 

PMID- 24114135
TI  - When you can have the bird without shooting it!: Extramacular enhanced depth
      optical coherence tomography in birdshot chorioretinopathy.

PMID- 24114136
TI  - When you can have the bird without shooting it!: Extramacular enhanced depth
      optical coherence tomography in birdshot chorioretinopathy--reply.

PMID- 24114137
TI  - Complications of pneumatic retinopexy.

PMID- 24114138
TI  - Complications of pneumatic retinopexy--reply.

PMID- 24114139
TI  - Detection of antiretinal autoantibodies in serum by Western blotting.

PMID- 24114140
TI  - Detection of antiretinal autoantibodies in serum by Western blotting--reply.

PMID- 24114141
TI  - Recurrent herpes simplex keratitis adjacent to femtosecond laser arcuate
      keratotomies.

PMID- 24114142
TI  - Near-field electrospinning of light-emitting conjugated polymer nanofibers.
AB  - The authors report on the realization of ordered arrays of light-emitting
      conjugated polymer nanofibers by near-field electrospinning. The fibers, made
      from poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene], have diameters of
      a few hundreds of nanometers and their emission peaked at 560 nm. The observed
      blue-shift compared to the emission from reference films is attributed to
      different polymer packing in the nanostructures. Optical confinement in the
      fibers is also analyzed through self-waveguided emission. These results open
      interesting perspectives for the realization of complex and ordered architectures
      by light-emitting nanofibers, such as photonic circuits, and for the precise
      positioning and integration of conjugated polymer fibers into light-emitting
      devices. 

PMID- 24114143
TI  - CD8(+) T-cell priming and boosting: more antigen-presenting DC, or more antigen
      per DC?
AB  - RNA transfection is a standard method to load dendritic cells (DC) with antigen
      for therapeutic cancer vaccination. While electroporation yields high
      transfection efficiency and satisfying expression levels, lipofection results in
      only few cells expressing high amounts of antigen. We compared antigen loading of
      human monocyte-derived DC by MelanA RNA electroporation and lipofection. No
      differences in phenotype or migrational capacity were detected, but lipofected DC
      induced stronger cytokine secretion by antigen-specific T cells and were superior
      in priming and boosting of MelanA-specific CD8(+) T cells. Interestingly, T cells
      stimulated with the differently transfected DC did not differ in their functional
      avidity. To determine whether the amount of antigen per cell is indeed
      responsible for the superiority of the lipofected DC, we increased the amount of
      MelanA RNA fivefold and mixed those DC with mock-electroporated ones to mimic the
      antigen distribution of lipofected cells. This significantly improved the
      stimulatory capacity, indicating that indeed the amount of antigen per cell seems
      to be the responsible feature for the observed superiority of lipofected DCs.
      These data suggest that a few DC that express high amounts of antigen are more
      immunogenic than many DC expressing lower amounts, although this needs to be
      tested in a two-armed immunogenicity trial.

PMID- 24114144
TI  - Expansion of CD11b(+)Ly6G (+)Ly6C (int) cells driven by medroxyprogesterone
      acetate in mice bearing breast tumors restrains NK cell effector functions.
AB  - The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a
      hormone replacement therapy in postmenopausal women and as contraceptive.
      However, prolonged administration of MPA is associated with increased incidence
      of breast cancer through ill-defined mechanisms. Here, we explored whether
      exposure to MPA during mammary tumor growth affects myeloid-derived suppressor
      cells (MDSCs; CD11b(+)Gr-1(+), mostly CD11b(+)Ly6G(+)Ly6C(int) and CD11b(+)Ly6G(
      )Ly6C(high) cells) and natural killer (NK) cells, potentially restraining tumor
      immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does
      not express the classical progesterone receptor and expands MDSCs) to challenge
      BALB/c mice in the absence or in the presence of MPA. We observed that MPA
      promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with
      reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA
      induced a preferential expansion of CD11b(+)Ly6G(+)Ly6C(int) cells in spleen and
      bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear
      mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these
      cells with the ability to promote a preferential differentiation of bone marrow
      cells into CD11b(+)Ly6G(+)Ly6C(int) cells that displayed suppressive activity on
      NK cell degranulation. Sorted CD11b(+)Gr-1(+) cells from MPA-treated tumor
      bearing mice exhibited higher suppressive activity on NK cell degranulation than
      CD11b(+)Gr-1(+) cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting
      through the GR, endows tumor cells with an enhanced capacity to expand
      CD11b(+)Ly6G(+)Ly6C(int) cells that subsequently display a stronger suppression
      of NK cell-mediated anti-tumor immunity. Our results describe an alternative
      mechanism by which MPA may affect immunosurveillance and have potential
      implication in breast cancer incidence.

PMID- 24114145
TI  - Understanding the anatomy of dystonia: determinants of penetrance and phenotype.
AB  - The dystonias comprise a group of syndromes characterized by prolonged
      involuntary muscle contractions resulting in repetitive movements and abnormal
      postures. Primary dystonia has been associated with over 14 different genotypes,
      most of which follow an autosomal dominant inheritance pattern with reduced
      penetrance. Independent of etiology, the disease is characterized by extensive
      variability in disease phenotype and clinical severity. Recent neuroimaging
      studies investigating this phenomenon in manifesting and non-manifesting genetic
      carriers of dystonia have discovered microstructural integrity differences in the
      cerebello-thalamo-cortical tract in both groups related to disease penetrance.
      Further study suggests these differences to be specific to subrolandic white
      matter regions somatotopically related to clinical phenotype. Clinical severity
      was correlated to the degree of microstructural change. These findings suggest a
      mechanism for the penetrance and clinical variability observed in dystonia and
      may represent a novel therapeutic target for patients with refractory limb
      symptoms. 

PMID- 24114146
TI  - Association between hospital case volume and the use of bronchoscopy and
      esophagoscopy during head and neck cancer diagnostic evaluation.
AB  - BACKGROUND: There are no clinical guidelines on best practices for the use of
      bronchoscopy and esophagoscopy in diagnosing head and neck cancer. This
      retrospective cohort study examined variation in the use of bronchoscopy and
      esophagoscopy across hospitals in Michigan. METHODS: A total of 17,828 patients
      were identified with head and neck cancer in the 2006 to 2010 Michigan State
      Ambulatory Surgery Databases. A hierarchical, mixed-effect logistic regression
      was used to examine whether a hospital's risk-adjusted rate of concurrent
      bronchoscopy or esophagoscopy was associated with its case volume (< 100, 100
      999, or >= 1000 cases per hospital) for those undergoing diagnostic laryngoscopy.
      RESULTS: Of 9218 patients undergoing diagnostic laryngoscopy, 1191 (12.9%)
      received concurrent bronchoscopy and 1675 (18.2%) underwent concurrent
      esophagoscopy. The median hospital rate of bronchoscopy was 2.7% (range, 0%
      61.1%), and low-volume (odds ratio [OR] = 27.1; 95% confidence interval [CI] =
      1.9, 390.7) and medium-volume (OR = 28.1; 95% CI = 2.0, 399.0) hospitals were
      more likely to perform concurrent bronchoscopy compared to high-volume hospitals.
      The median hospital rate of esophagoscopy was 5.1% (range, 0%-47.1%), and low
      volume (OR = 9.8; 95% CI = 1.5, 63.7) and medium-volume (OR = 8.5; 95% CI = 1.3,
      55.0) hospitals were significantly more likely to perform concurrent
      esophagoscopy relative to high-volume hospitals. CONCLUSIONS: Patients with head
      and neck cancer who are undergoing diagnostic laryngoscopy are much more likely
      to undergo concurrent bronchoscopy and esophagoscopy at low- and medium-volume
      hospitals than at high-volume hospitals. Whether this represents overuse of
      concurrent procedures or appropriate care that leads to earlier diagnosis and
      better outcomes merits further investigation.

PMID- 24114147
TI  - Genomic analysis of pandemic and post-pandemic influenza A pH1N1 viruses isolated
      in Rio Grande do Sul, Brazil.
AB  - During the 2009 influenza A pH1N1 pandemics in Brazil, the state that was most
      affected was Rio Grande do Sul (RS), with over 3,000 confirmed cases, including
      298 deaths. While no cases were confirmed in 2010, 103 infections with 14 deaths
      by pH1N1 were reported in 2011. Genomic analysis of the circulating viruses is
      fundamental for understanding viral evolution and supporting vaccine development
      against these pathogens. This study investigated whole genomes of six pH1N1 virus
      isolates from pandemic and post-pandemic periods in RS, Brazil. Phylogenetic
      analysis using the concatenated genome segments demonstrated that at least two
      lineages of the virus co-circulated in RS during the 2009 pandemic period.
      Moreover, our analysis showed that the post-pandemic pH1N1 virus from 2011
      constitutes a distinct clade whose ancestor belongs to clade 7. All six isolates
      contained amino acid substitutions in their proteins when compared to the
      archetype strains California/04/2009 and California/07/2009. The 2011 isolates
      contained more amino acid substitutions, and most of their genes were under
      purifying selection. Based on the amino acid substitutions in HA epitopes from
      strains isolated in RS, Brazil, in silico analysis predicted a decrease in
      vaccine efficacy against post-pandemic strains (median 31.562 %) in relation to
      pandemic ones (median 39.735 %). 

PMID- 24114148
TI  - Association of meteorological factors with childhood viral acute respiratory
      infections in subtropical China: an analysis over 11 years.
AB  - The objective of this study was to obtain a better understanding of the effects
      of meteorological factors on the prevalence and seasonality of common respiratory
      viruses in China, which has a subtropical climate. A retrospective study was
      conducted by identifying children admitted to a hospital with acute respiratory
      infections due to seven common viruses between January 2001 and December 2011. A
      total of 42,104 nasopharyngeal samples were tested for respiratory syncytial
      virus (RSV), influenza A and B viruses (IV-A and IV-B), parainfluenza viruses 1-3
      (PIV-1, PIV-2, PIV-3), and adenovirus (ADV) by direct immunofluorescence assay.
      Meteorological data were obtained from Suzhou Weather Bureau. Correlations of
      viral prevalence with meteorological factors were evaluated using Spearman rank
      correlation and partial correlation. Multivariate time-series analysis including
      an autoregressive integrated moving average (ARIMA) model and generalized linear
      Poisson models was conducted to study the effect of meteorological factors on the
      prevalence of respiratory virus infection. RSV and IV-A activity showed
      distinctive winter peak, whereas PIV-3 and ADV peaked in the summer. Incidence of
      RSV was correlated with low environmental temperature, and PIV-3 only with high
      temperature. IV-A activity was correlated with both low temperature and high
      relative humidity. ADV activity was correlated with high total rainfall. In the
      ARIMA model, RSV-associated hospitalizations were predictable, and the monthly
      number of RSV cases decreased by 11.25 % (95 % CI: 5.34 % to 16.79 %) for every 1
      degrees C increase in the average temperature. Seasonality of certain
      respiratory virus may be explained by meteorological influences. The impact of
      meteorological factors on the prevalence of RSV may be useful for predicting the
      activity of this virus. 

PMID- 24114150
TI  - Anatase TiO2 nanorod-decoration for highly efficient photoenergy conversion.
AB  - In recent studies of inorganic materials for energy applications, surface
      modification processes have been shown to be among the most effective methods to
      enhance the performance of devices. Here, we demonstrate a facile nano-decoration
      method which is generally applicable to anatase TiO2 nanostructures, as well as a
      nano-decorated hierarchical TiO2 nanostructure which improves the energy
      conversion efficiency of a dye-sensitized solar cell (DSSC). Using a facile sol
      gel method, 0-D, 1-D, and 2-D type anatase TiO2 nanostructures were decorated
      with 200 nm long anatase TiO2 nanorods to create various hierarchical
      nanostructures. A structural analysis reveals that the branched nanorod has a
      highly crystalline anatase phase with anisotropic growth in the [001]
      longitudinal direction. When one of the hierarchical structures, a chestnut bur
      like nanostructure, was employed in a dye-sensitized solar cell as a scattering
      layer, offering increased dye-loading properties, preserving a sufficient level
      of light-scattering ability and preserving superior charge transport and
      recombination properties as well, the energy conversion efficiency of the cell
      improved by 19% (from 7.16% to 9.09%) compared to a cell with a 0-D TiO2 sphere
      as a scattering layer. This generally applicable anatase nanorod-decorating
      method offers potential applications in various energy-conversion applications,
      especially in DSSCs, quantum-dot solar cells, photoelectrochemical water
      splitting devices, photocatalysis, and lithium ion batteries. 

PMID- 24114149
TI  - CD8+ Treg cells suppress CD8+ T cell-responses by IL-10-dependent mechanism
      during H5N1 influenza virus infection.
AB  - Although Treg-cell-mediated suppression during infection or autoimmunity has been
      described, functions of Treg cells during highly pathogenic avian influenza virus
      infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic
      mice, CD8(+) Foxp3(+) Treg cells, but not CD4(+) Foxp3(+) Treg cells, were
      remarkably induced during H5N1 infection. In addition to expressing CD25, the
      CD8(+) Foxp3(+) Treg cells showed a high level of GITR and produced IL-10. In an
      adoptive transfer model, CD8(+) Treg cells suppressed CD8(+) T-cell responses and
      promoted H5N1 virus infection, resulting in enhanced mortality and increased
      virus load in the lung. Furthermore, in vitro neutralization of IL-10 and studies
      with IL-10R-deficient mice in vitro and in vivo demonstrated an important role
      for IL-10 production in the capacity of CD8(+) Treg cells to inhibit CD8(+) T
      cell responses. Our findings identify a previously unrecognized role of CD8(+)
      Treg cells in the negative regulation of CD8(+) T-cell responses and suggest that
      modulation of CD8(+) Treg cells may be a therapeutic strategy to control H5N1
      viral infection. 

PMID- 24114152
TI  - Prevention of problem behavior by teaching functional communication and self
      control skills to preschoolers.
AB  - We evaluated the effects of the preschool life skills program (PLS; Hanley, Heal,
      Tiger, & Ingvarsson, 2007) on the acquisition and maintenance of functional
      communication and self-control skills, as well as its effect on problem behavior,
      of small groups of preschoolers at risk for school failure. Six children were
      taught to request teacher attention, teacher assistance, and preferred materials,
      and to tolerate delays to and denial of those events during child-led, small
      group activities. Teaching strategies included instruction, modeling, role play,
      and differential reinforcement. Six additional children randomly assigned to
      similarly sized control groups participated in small-group activities but did not
      experience the PLS program. Within-subject and between-groups designs showed that
      the PLS teaching procedures were functionally related to the improvements and
      maintenance of the skills and prevention of problem behavior. Stakeholder
      responses on a social acceptability questionnaire indicated that they were
      satisfied with the form of the targeted social skills, the improvements in the
      children's performance, and the teaching strategies.

PMID- 24114151
TI  - How do life-course trajectories of socioeconomic position affect quality of life
      in patients with diabetes mellitus?
AB  - PURPOSE: This study evaluated the association of life-course economic trajectory
      with health-related quality of life in patients with diabetes mellitus. METHODS:
      The study subjects were 183 outpatients over 20 years of age with diabetes
      mellitus. A questionnaire was administered to collect information about current
      and childhood economic status, and health-related quality of life was assessed
      through the 12-item short-form health survey (SF-12). Economic trajectory was
      categorized into five groups according to the change between current and
      childhood economic status. The mental component summary score and physical
      component summary score of the SF-12 were compared with average scores for the US
      population due to lack of domestic data. RESULTS: Physical health-related quality
      of life was more likely to be affected by current economic status than by
      economic position in childhood. On the other hand, mental health-related quality
      of life was associated not only with the self-rated economic status (p = 0.01)
      but also socioeconomic trajectory (p = 0.04), even after controlling for
      potential confounding factors. These results suggest that early economic status
      may affect mental health throughout one's lifetime. CONCLUSIONS: Economic status
      and trajectory throughout life may influence health-related quality of life in
      patients with diabetes mellitus.

PMID- 24114153
TI  - Effects of a reduced time-out interval on compliance with the time-out
      instruction.
AB  - Time-out is a negative punishment procedure that parents and teachers commonly
      use to reduce problem behavior; however, specific time-out parameters have not
      been evaluated adequately. One parameter that has received relatively little
      attention in the literature is the mode of administration (verbal or physical) of
      time-out. In this study, we evaluated a procedure designed to reduce problem
      behavior and increase compliance with the verbal instruction to go to time-out.
      Specifically, we reduced the time-out interval contingent on compliance with the
      time-out instruction. Six preschool-aged boys participated in the study. Time-out
      effectively reduced the problem behavior of all 6 participants, and the procedure
      to increase compliance with the time-out instruction was effective for 4 of 6
      participants. 

PMID- 24114154
TI  - An evaluation of programmed treatment-integrity errors during discrete-trial
      instruction.
AB  - This study evaluated the effects of programmed treatment-integrity errors on
      skill acquisition for children with an autism spectrum disorder (ASD) during
      discrete-trial instruction (DTI). In Study 1, we identified common treatment
      integrity errors that occur during academic instruction in schools. In Study 2,
      we simultaneously manipulated 3 integrity errors during DTI. In Study 3, we
      evaluated the effects of each of the 3 integrity errors separately on skill
      acquisition during DTI. Results showed that participants either demonstrated
      slower skill acquisition or did not acquire the target skills when instruction
      included treatment-integrity errors. 

PMID- 24114155
TI  - Performance pay improves engagement, progress, and satisfaction in computer-based
      job skills training of low-income adults.
AB  - Advancing the education of low-income adults could increase employment and
      income, but adult education programs have not successfully engaged low-income
      adults. Monetary reinforcement may be effective in promoting progress in adult
      education. This experiment evaluated the benefits of providing incentives for
      performance in a job-skills training program for low-income, unemployed adults.
      Participants worked on typing and keypad programs for 7 months. Participants
      randomly assigned to Group A (n = 23) earned hourly and productivity pay on the
      typing program (productivity pay), but earned only equalized hourly pay on the
      keypad program (hourly pay). Group B (n = 19) participants had the opposite
      contingencies. Participants worked more on, advanced further on, and preferred
      their productivity pay program. These results show that monetary incentives can
      increase performance in a job-skills training program, and indicate that payment
      in adult education programs should be delivered contingent on performance in the
      training program instead of simply on attendance. 

PMID- 24114156
TI  - Treating stereotypy in adolescents diagnosed with autism by refining the tactic
      of "using stereotypy as reinforcement".
AB  - Use of automatically reinforced stereotypy as reinforcement has been shown to be
      successful for increasing socially desirable behaviors in persons with
      intellectual disabilities (Charlop, Kurtz, & Casey, 1990; Hanley, Iwata,
      Thompson, & Lindberg, 2000; Hung, 1978). A component analysis of this treatment
      was conducted with 3 adolescents who had been diagnosed with autism, and then
      extended by (a) progressively increasing the quantitative and qualitative aspects
      of the response requirement to earn access to stereotypy, (b) arranging objective
      measures of client preference for contingent access to stereotypy compared to
      other relevant treatments for their automatically reinforced stereotypy, and (c)
      assessing the social validity of this treatment with other relevant stakeholders.
      Implications for addressing stereotypy and increasing the leisure skills of
      adolescents with autism are discussed. 

PMID- 24114157
TI  - On the representativeness of behavior observation samples in classrooms.
AB  - School consultants who rely on direct observation typically conduct observational
      samples (e.g., 1 30-min observation per day) with the hopes that the sample is
      representative of performance during the remainder of the day, but the
      representativeness of these samples is unclear. In the current study, we recorded
      the problem behavior of 3 referred students for 4 consecutive school days between
      9:30 a.m. and 2:30 p.m. using duration recording in consecutive 10-min sessions.
      We then culled 10-min, 20-min, 30-min, and 60-min observations from the complete
      record and compared these observations to the true daily mean to assess their
      accuracy (i.e., how well individual observations represented the daily occurrence
      of target behaviors). The results indicated that when behavior occurred with low
      variability, the majority of brief observations were representative of the
      overall levels; however, when behavior occurred with greater variability, even 60
      min observations did not accurately capture the true levels of behavior. 

PMID- 24114158
TI  - On the efficacy of a computer-based program to teach visual Braille reading.
AB  - Scheithauer and Tiger (2012) created an efficient computerized program that
      taught 4 sighted college students to select text letters when presented with
      visual depictions of Braille alphabetic characters and resulted in the emergence
      of some braille reading. The current study extended these results to a larger
      sample (n = 81) and compared the efficacy and efficiency of the instructional
      program using 2 different response modalities. One variation of the program
      required a response in a multiple-choice format, and the other variation required
      a keyed response. Both instructional programs resulted in increased braille
      letter identification and braille reading. These skills were maintained at a
      follow-up session 7 to 14 days later. The mean time needed to complete the
      program was 22.8 min across participants. Implications of these results for
      future research, as well as practical implications for teaching the braille
      alphabet, are discussed.

PMID- 24114159
TI  - An evaluation of generalization of mands during functional communication
      training.
AB  - The primary purpose of this study was to evaluate the generalization of mands
      during functional communication training (FCT) and sign language training across
      functional contexts (i.e., positive reinforcement, negative reinforcement). A
      secondary purpose was to evaluate a training procedure based on stimulus control
      to teach manual signs. During the treatment evaluation, we implemented sign
      language training in 1 functional context (e.g., positive reinforcement by
      attention) while continuing the functional analysis conditions in 2 other
      contexts (e.g., positive reinforcement by tangible item; negative reinforcement
      by escape). During the generalization evaluation, we tested for the
      generalization of trained mands across functional contexts (i.e., positive
      reinforcement; negative reinforcement) by implementing extinction in the 2
      nontarget contexts. The results suggested that the stimulus control training
      procedure effectively taught manual signs and treated destructive behavior.
      Specific patterns of generalization of trained mands and destructive behavior
      also were observed. 

PMID- 24114160
TI  - Evaluation of some components of choice making.
AB  - Providing access to choice-making opportunities is a useful addition to
      behavioral interventions, although the critical features of choice making may
      differ greatly across individuals. In this study, results of an initial 3-choice
      concurrent-operants preference assessment with 4 subjects with autism spectrum
      disorder suggested that 2 subjects preferred the choice-making condition and
      participated in subsequent assessments to examine the potential influences of
      reinforcer variability and differential access to high-preference reinforcers on
      their preferences for choice making. Two other subjects did not prefer the choice
      making condition and participated in subsequent assessments to explore conditions
      under which they might prefer choice-making opportunities. Results suggested that
      a wide range of variables influenced preference for choice-making conditions. 

PMID- 24114161
TI  - Training adults with an autism spectrum disorder to conduct discrete-trial
      training for young children with autism: a pilot study.
AB  - We evaluated a behavioral skills training program for adults with autism spectrum
      disorder and mild or no intellectual disabilities who were interested in learning
      the skills used by behavior therapists to work with young children with autism
      and other developmental disabilities. Four adults, aged 21 to 30 years,
      participated. We trained each individually using verbal and written instructions,
      modeling, and role play with feedback to teach 2 basic skills to an adult who
      played the role of a young child with autism. We evaluated generalization of the
      discrete-trial training skills by having the participant (a) teach the adult
      confederate 2 additional targets that we had not included in training and (b)
      teach a new skill to a young child with autism. Results indicated that 3 of the 4
      participants rapidly acquired discrete-trial training skills and that these
      skills generalized to new targets with the confederate adults and to teaching an
      actual child with autism. 

PMID- 24114162
TI  - Quantifying contingent relations from direct observation data: transitional
      probability comparisons versus Yule's Q.
AB  - Measuring contingencies or sequential associations may be applied to a broad
      range of response-stimulus, stimulus-stimulus, or response-response relations.
      Within behavior analysis, response-stimulus contingencies have been quantified by
      comparing 2 transitional probabilities and plotting them in contingency space.
      Within and outside behavior analysis, Yule's Q has become a recommended statistic
      used to quantify sequential associations between 2 events. In the current paper,
      we identify 2 methods of transitional probability comparisons used in the
      behavior-analytic literature to estimate contingencies in natural settings. We
      compare each of these methods to the more established Yule's Q statistic and
      evaluate relations between each pair of indices. Advantages and disadvantages of
      each method are identified, with recommendations as to which approach may be most
      appropriate for measuring contingencies. 

PMID- 24114163
TI  - Some guidelines for conducting research in applied behavioral pharmacology.
AB  - The Journal of Applied Behavior Analysis (JABA) has published a number of
      articles on the behavioral effects of psychomotor stimulant drugs in individuals
      with attention deficit hyperactivity disorder. Some additional JABA publications
      have included investigations of the behavioral effects of other drugs. However, a
      review of these articles revealed many methodological differences among studies,
      which makes it difficult to evaluate the relative contribution of each research
      effort to the overall database. In this context, we offer some guidelines to
      solidify the methodological rigor of behavior pharmacological research published
      in JABA. 

PMID- 24114164
TI  - Assessment of problem behavior evoked by disruption of ritualistic toy
      arrangements in a child with autism.
AB  - A functional analysis suggested that the problem behavior of a 9-year-old girl
      with autism was maintained by gaining the opportunity to restore ritualistic toy
      arrangements that had been disrupted. Functional communication training and
      extinction produced clear decreases in problem behavior in 2 contexts: 1 in which
      we removed a play item, and 1 in which we merely relocated the item and blocked
      its rearrangement. 

PMID- 24114165
TI  - Delay discounting of hypothetical and real money: the effect of holding
      reinforcement rate constant.
AB  - We examined the effect of holding reinforcement rate constant on delay
      discounting of hypothetical and real money when delays were actually experienced.
      In some conditions, participants were required to wait for the delayed rewards,
      and in some conditions, reinforcement rate was held constant by adding blackout
      periods after immediate rewards. Typical discounting occurred with the standard
      procedure and when there were no blackouts, but not when we held rate of
      reinforcement constant. Real and hypothetical money produced the same outcomes. 

PMID- 24114166
TI  - The effects of verbal instruction and shaping to improve tackling by high school
      football players.
AB  - We evaluated verbal instruction and shaping using TAG (teaching with acoustical
      guidance) to improve tackling by 3 high school football players. Verbal
      instruction and shaping improved tackling for all 3 participants. In addition,
      performance was maintained as participants moved more quickly through the
      tackling procedure. 

PMID- 24114167
TI  - Effects of preference on the emergence of untrained verbal operants.
AB  - The current study replicated and extended the findings of Wallace, Iwata, and
      Hanley (2006), who demonstrated conditions that facilitated the transfer from
      tact to mand relations. Students in the current study were taught to tact both
      high-preference (HP) and low-preference (LP) items and subsequently were assessed
      on their ability to mand for those items. The results showed the emergence of
      mands for HP items but not LP items following tact training. 

PMID- 24114168
TI  - Teaching young adults with disabilities to respond appropriately to lures from
      strangers.
AB  - We taught 5 adults with mild intellectual disabilities to respond appropriately
      to lures from strangers. Skills were taught in the classroom first and then in
      situ. Before training, participants did not walk away from confederate strangers
      who tried to lure them away. Participants demonstrated appropriate responses
      during classroom and in situ training, although performance during assessments
      was somewhat inconsistent. Appropriate responses were observed during weekly
      maintenance probes and at follow-up assessments for up to 3 months after
      training. 

PMID- 24114169
TI  - An evaluation of repeating the discriminative stimulus when using least-to-most
      prompting to teach intraverbal behavior to children with autism.
AB  - A common recommendation with least-to-most prompting is to repeat the
      discriminative stimulus (S(D) ) with each successive prompt (Cooper, Heron, &
      Heward, 2007). However, few studies have evaluated this recommendation. We
      compared repeating the S(D) to presenting the S(D) once when teaching intraverbal
      behavior to children with autism. Results showed that both methods produced
      acquisition, and repeating the S(D) produced no greater efficiency in
      acquisition. 

PMID- 24114170
TI  - An evaluation of texture manipulations to increase swallowing.
AB  - The purpose of the current investigation was to identify an appropriate texture
      for initial treatment of 1 child's feeding problem. Variability in mouth clean (a
      product measure of swallowing) during a texture assessment suggested that
      individual pureed foods differentially affected feeding behavior. A single-food
      assessment identified individual problematic foods. We used the results of these
      assessments to inform treatment, resulting in high levels of mouth clean across
      foods. 

PMID- 24114171
TI  - Assessment and treatment of vocal stereotypy associated with television: a pilot
      study.
AB  - A 6-year-old boy who had been diagnosed with autism participated in a pilot study
      that showed that (a) television was associated with increased vocal stereotypy
      and (b) sitting was associated with lower levels of vocal stereotypy.
      Subsequently, we reduced vocal stereotypy while the television was on by
      reinforcing sitting on a variable-interval schedule. Results suggest that
      conditional percentages may be useful for the identification of alternative
      behaviors as part of treatments for stereotypy. 

PMID- 24114172
TI  - Response interruption and redirection: current research trends and clinical
      application.
AB  - The objective of this paper is to provide a review of recent literature on
      response interruption and redirection (RIRD), a treatment for stereotypy. We
      discuss procedural variations and the potential mechanisms that are responsible
      for the effectiveness of RIRD. Clinical considerations and suggestions for future
      research are also discussed. 

PMID- 24114173
TI  - Anandamide produced by Ca(2+)-insensitive enzymes induces excitation in primary
      sensory neurons.
AB  - The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other
      effects, has been shown to be involved in nociceptive processing both in the
      central and peripheral nervous systems. Anandamide is thought to be synthesised
      by several enzymatic pathways both in a Ca(2+)-sensitive and Ca(2+)-insensitive
      manner, and rat primary sensory neurons produce anandamide. Here, we show for the
      first time, that cultured rat primary sensory neurons express at least four of
      the five known Ca(2+)-insensitive enzymes implicated in the synthesis of
      anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
      N-arachidonoyl, the common substrate of the anandamide-synthesising pathways,
      results in anandamide production which is not changed by the removal of
      extracellular Ca(2+). We also show that anandamide, which has been synthesised in
      primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-N-arachidonoyl induces a transient receptor potential
      vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by
      concomitant activation of the cannabinoid type 1 receptor. Finally, we show that
      sub-populations of transient receptor potential vanilloid type 1 ion channel
      expressing primary sensory neurons also express some of the putative Ca(2+)
      insensitive anandamide-synthesising enzymes. Together, these findings indicate
      that anandamide synthesised by primary sensory neuron via a Ca(2+)-insensitive
      manner has an excitatory rather than an inhibitory role in primary sensory
      neurons and that excitation is mediated predominantly through autocrine
      signalling. Regulation of the activity of the Ca(2+)-insensitive anandamide
      synthesising enzymes in these neurons may be capable of regulating the activity
      of these cells, with potential relevance to controlling nociceptive processing. 

PMID- 24114174
TI  - Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with
      the beta1 and beta3 but not beta2 adrenergic receptors, and induces apoptosis.
AB  - Hydrogen sulfide (H2S) as a novel gasotransmitter regulates variety of processes,
      including calcium transport systems. Sodium calcium exchanger (NCX) is one of the
      key players in a regulation calcium homeostasis. Thus, the aims of our work were
      to determine effect of sulfide signaling on the NCX type 1 (NCX1) expression and
      function in HeLa cells, to investigate the relationship of beta-adrenergic
      receptors with the NCX1 in the presence and/or absence of H2S, and to determine
      physiological importance of this potential communication. As a H2S donor, we used
      morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate-GYY4137. We
      observed increased levels of the NCX1 mRNA, protein, and activity after 24 h of
      GYY4137 treatment. This increase was accompanied by elevated cAMP due to the
      GYY4137 treatment, which was completely abolished, when NCX1 was silenced.
      Increased cAMP levels would point to upregulation of beta-adrenergic receptors.
      Indeed, GYY4137 increased expression of beta1 and beta3 (but not beta2)
      adrenergic receptors. These receptors co-precipitated, co-localized with the
      NCX1, and induced apoptosis in the presence of H2S. Our results suggest that
      sulfide signaling plays a role in regulation of the NCX1, beta1 and beta3
      adrenergic receptors, their co-localization, and stimulation of apoptosis, which
      might be of a potential importance in cancer treatment.

PMID- 24114175
TI  - Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family.
AB  - The SLC13 family in humans and other mammals consists of sodium-coupled
      transporters for anionic substrates: three transporters for
      dicarboxylates/citrate and two transporters for sulfate. This review will focus
      on the di- and tricarboxylate transporters: NaDC1 (SLC13A2), NaDC3 (SLC13A3), and
      NaCT (SLC13A5). The substrates of these transporters are metabolic intermediates
      of the citric acid cycle, including citrate, succinate, and alpha-ketoglutarate,
      which can exert signaling effects through specific receptors or can affect
      metabolic enzymes directly. The SLC13 transporters are important for regulating
      plasma, urinary and tissue levels of these metabolites. NaDC1, primarily found on
      the apical membranes of renal proximal tubule and small intestinal cells, is
      involved in regulating urinary levels of citrate and plays a role in kidney stone
      development. NaDC3 has a wider tissue distribution and high substrate affinity
      compared with NaDC1. NaDC3 participates in drug and xenobiotic excretion through
      interactions with organic anion transporters. NaCT is primarily a citrate
      transporter located in the liver and brain, and its activity may regulate
      metabolic processes. The recent crystal structure of the Vibrio cholerae homolog,
      VcINDY, provides a new framework for understanding the mechanism of transport in
      this family. This review summarizes current knowledge of the structure, function,
      and regulation of the di- and tricarboxylate transporters of the SLC13 family. 

PMID- 24114176
TI  - Critical role for peripherally-derived interleukin-10 in mediating the
      thermoregulatory manifestations of fever and hypothermia in severe forms of
      lipopolysaccharide-induced inflammation.
AB  - Although peripherally released interleukin (IL)-10 has a critical regulatory role
      in limiting fever in mild-to-moderate forms of inflammation, its role in
      regulating the more complex thermoregulatory manifestations of hypothermia and
      fever noted during severe inflammation is less clear. Using cytokine antagonism,
      we therefore investigated the involvement of peripherally released IL-10 in
      mediating hypothermia, fever and inflammation induced by intraperitoneal (IP)
      administration of a large dose of lipopolysaccharide (LPS). Male Wistar rats (200
      250 g) were anaesthetized and implanted intra-abdominally with temperature
      sensitive radiotelemeters. Rats were randomly assigned to receive IL-10 antiserum
      (IL-10AS) or normal sheep serum IP, 4 h before receiving an IP injection of LPS
      (10 mg/kg) or phosphate-buffered saline (PBS). Inflammatory responses were
      measured in plasma and tissue samples (spleen, liver and brain) at 90 min and 6 h
      after the IP injection of LPS or PBS. Administration of LPS induced an initial
      period of hypothermia (~90 min) after which fever developed. Pre-treating rats
      with IL-10AS abolished the LPS-induced increase in plasma IL-10 levels,
      attenuated the hypothermia and increased the amplitude of the fever. Moreover, IL
      10AS pre-treatment augmented the LPS-induced increase in plasma levels of tumor
      necrosis factor-alpha (90 min and 6 h), IL-1beta (90 min), prostaglandin E2 (90
      min) and IL-6 (6 h), in the periphery, but not the hypothalamus, over the
      duration of hypothermia and fever. Via its action on the synthesis of
      inflammatory mediators in the spleen and liver, endogenous IL-10 plays a crucial
      regulatory role in mediating hypothermia and fever during severe aspectic (LPS
      induced) systemic inflammation.

PMID- 24114178
TI  - Yet another polymorph of alpha-synuclein: solid-state sequential assignments.
AB  - Parkinson's disease is a neurological human proteinopathy, which is caused by the
      accumulation of protein aggregates of high molecular mass. alpha-Synuclein is a
      major component of these fibrillar, beta-sheet rich, insoluble assemblies and is
      deposited in the form of amyloids. Structural characterization of amyloids is
      possible by solid-state NMR, although no atomic-resolution structure is available
      as of today. alpha-Synuclein, as many other pathology-related fibril-forming
      proteins, can form a number of different polymorphs that are sometimes tricky to
      obtain in pure form. Here, we describe the chemical shifts and secondary
      structure analysis of a polymorph that also adopts mainly beta-sheet
      conformation, with a fibrillar core ranging from residues 38 to 94. In addition,
      residues 15-20 from the N-terminus found to be part of a rigid ordered beta
      sheet. The chemical shifts differ substantially from the polymorph we previously
      assigned. 

PMID- 24114177
TI  - A comparison of in vitro ADME properties and pharmacokinetics of azithromycin and
      selected 15-membered ring macrolides in rodents.
AB  - The purpose of this study was to evaluate the impact of structural modifications
      on the 15-membered macrolactone ring and/or substituents on the in vitro ADME
      properties and in vivo pharmacokinetic (PK) profile for selected derivatives in
      rodents in comparison to azithromycin. Azithromycin and seven selected 15
      membered macrolide derivatives, modified either by removal of the sugar moieties,
      replacement of the amine with a lactam, or addition of lipophilic substituents,
      were screened in several in vitro ADME assays and in vivo PK studies in rodents.
      In vitro ADME profiling included assessment of passive permeability and P-gp
      substrate, metabolic stability in liver microsomes and hepatocytes, as well as
      CYP direct inhibition measurements. In vivo PK studies were performed in rats
      (Sprague-Dawley), mice (Balb/c), and P-gp wild-type and deficient mice (CF-1TM).
      Different structural modifications on the azithromycin scaffold resulted in
      substantial changes in disposition kinetics and oral bioavailability in both
      rodent species. However, these differences in vivo cannot be predicted based on
      in vitro results since most of these molecules are classified in the same
      category. Therefore, in the case of 15-membered ring macrolides, the in vitro
      ADME screens presented here seem to have low predictive value for in vivo
      prediction, making their use as routine in vitro screens prior to PK assessments
      questionable. 

PMID- 24114179
TI  - Animal welfare at the group level: more than the sum of individual welfare?
AB  - Currently assessment and management of animal welfare are based on the
      supposition that welfare status is something experienced identically by each
      individual animal when exposed to the same conditions. However, many authors
      argue that individual welfare cannot be seen as an 'objective' state, but is
      based on the animal's own self-perception; such perception might vary
      significantly between individuals which appear to be exposed to exactly the same
      challenges. We argue that this has two implications: (1) actual perceived welfare
      status of individuals in a population may vary over a wide range even under
      identical environmental conditions; (2) animals that appear to an external
      observer to be in better or poorer welfare condition may all in fact perceive
      their own individual status as the same. This would imply that optimum welfare of
      a social group might be achieved in situations where individual group members
      differ markedly in apparent welfare status and perceive their own welfare as
      being optimal under differing circumstances. Welfare phenotypes may also vary
      along a continuum between self-regarding and other-regarding behaviour; a variety
      of situations exist where (social) individuals appear to invest in the welfare of
      other individuals instead of maximising their own welfare; in such a case it is
      necessary to re-evaluate individual welfare within the context of a social group
      and recognise that there may be consequences for the welfare of individuals, of
      decisions made at the group level or by other group members. 

PMID- 24114181
TI  - Comparison of the photophysical properties of three phenothiazine derivatives:
      transient detection and singlet oxygen production.
AB  - New methylene blue (NMB+) and methylene violet (MV) are known for their
      photosensitizing properties for singlet oxygen ((1)O2) generation upon visible
      light irradiation, and various examples of their use in the photodynamic
      inactivation of microorganisms and for photomedicinal purposes have been
      reported. However, their photophysical properties have never been extensively and
      systematically analyzed and compared. In the current work, we studied their
      absorption and fluorescence behavior relative to their parent compound, methylene
      blue (MB+), detected the transient species generated upon excitation of the
      photosensitizers and determined their quantum yields of singlet oxygen
      production. We could measure very high quantum yields of singlet oxygen
      production for all the studied compounds. NMB+ appeared similar to MB+, even
      though it produces (1)O2 much more efficiently, and was slightly influenced by
      the solvent. MV, in contrast, was much more sensitive to the chemical
      environment, and the transient species formed upon irradiation were different in
      methanol and acetonitrile. It appeared to be a very good singlet oxygen
      sensitizer, but the influence of the chemical environment should be carefully
      considered for any application. The comparative characterization of these
      sensitizers will represent a support for the determination and the understanding
      of the photochemical mechanisms occurring by using these phenothiazine dyes for
      various photobiological applications.

PMID- 24114180
TI  - A mixed culture of endophytic fungi increases production of antifungal
      polyketides.
AB  - Secondary metabolites produced by endophytic microorganisms can provide benefits
      to host plants, such as stimulating growth and enhancing the plant's resistance
      toward biotic and abiotic factors. During its life, a host plant may be inhabited
      by many species of endophytes within a restrictive environment. This condition
      can stimulate secondary metabolite production that improves microbial competition
      and may consequently affect both the neighboring microorganisms and the host
      plant. The interactions between the endophytes that co-habit the same host plant
      have been studied. However, the effect of these interactions on the host plant
      has remained neglected. When using mixed microbial cultures, we found that the
      endophytic fungus Alternaria tenuissima significantly increased the production of
      some polyketides, including antifungal stemphyperylenol in response to the
      endophytic Nigrospora sphaerica. Biological activity assays revealed that
      stemphyperylenol can cause cytotoxic effects against N. sphaerica, although no
      phytotoxicity was observed in the host plant Smallanthus sonchifolius, even at
      concentrations much higher than those toxic to the fungus. The polyketides
      produced by A. tenuissima may be important for the ecological relationships
      between endophyte-endophyte and endophytes-host plants in the natural
      environment. 

PMID- 24114182
TI  - Indications for and early complications associated with use of temporary invasive
      distraction for osteochondral graft transfer procedures for treatment of lateral
      osteochondral lesions of the talus.
AB  - BACKGROUND: A recent cadaveric study demonstrated that a novel technique termed
      temporary invasive distraction (TID), which uses intraoperative external
      fixation, can improve lateral talar dome exposure for osteochondral graft
      transfer procedures for treatment of lateral osteochondral lesions of the talus
      (OCLTs). The current study was performed to report our early complications using
      TID during open treatment of lateral OCLTs to determine whether this technique
      poses any risk of increased short-term patient morbidity. METHODS: Electronic and
      manual surgeon logs were searched for all cases of osteochondral graft
      procedures. Lateral lesions treated with TID were analyzed. Inpatient and
      outpatient medical records were reviewed for early complications associated with
      TID for this application to assess initial safety of this new technique.
      Complications were defined as pin tract infection, fracture, neurovascular
      injury, pin site pain, or pin site wound-healing problems. Complications were
      stratified into major and minor based on severity. Twelve consecutive patients
      had open osteochondral graft transfer procedures using temporary invasive
      distraction with and without fibular osteotomies. All patients were male, active
      duty US military service members with an average age of 38.4 (range, 23.8-52.5)
      years. RESULTS: Use of TID resulted in no early major complications and only 2
      early minor complications. Minor complications included 2 cases of residual
      postoperative pin site pain that resolved completely at 12 weeks postoperatively.
      By 12 weeks postoperatively, no patients demonstrated any residual complications
      or symptoms related to the use of TID. At mean latest follow-up of 90.5 weeks
      (20.9 months), there were no residual complications directly associated with the
      use of the TID device. CONCLUSIONS: Temporary invasive distraction with use of
      intraoperative external fixation can be safely performed with minimal risk of
      increased morbidity and offers potential technical advantages during open
      osteochondral graft transfer procedures for treatment of lateral OCLTs. LEVEL OF
      EVIDENCE: Level IV, retrospective chart study.

PMID- 24114183
TI  - Molecular determinants of the binding specificity of BH3 ligands to BclXL
      apoptotic repressor.
AB  - B-cell lymphoma extra-large protein (BclXL) serves as an apoptotic repressor by
      virtue of its ability to recognize and bind to BH3 domains found within a diverse
      array of proapoptotic regulators. Herein, we investigate the molecular basis of
      the specificity of the binding of proapoptotic BH3 ligands to BclXL. Our data
      reveal that while the BH3 ligands harboring the LXXX[A/S]D and [R/Q]XLXXXGD motif
      bind to BclXL with high affinity in the submicromolar range, those with the
      LXXXGD motif afford weak interactions. This suggests that the presence of a
      glycine at the fourth position (G+4)--relative to the N-terminal leucine (L0)
      within the LXXXGD motif--mitigates binding, unless the LXXXGD motif also contains
      arginine/glutamine at the -2 position. Of particular note is the observation that
      the residues at the +4 and -2 positions within the LXXX[A/S]D and [R/Q]XLXXXGD
      motifs appear to be energetically coupled-replacement of either [A/S]+4 or [R/Q]
      2 with other residues has little bearing on the binding affinity of BH3 ligands
      harboring one of these motifs. Collectively, our study lends new molecular
      insights into understanding the binding specificity of BH3 ligands to BclXL with
      important consequences on the design of novel anticancer drugs.

PMID- 24114184
TI  - The cross-talk between estrogen receptor and peroxisome proliferator-activated
      receptor gamma in thyroid cancer.
AB  - BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor
      gamma (PPARgamma) are associated with thyroid tumorigenesis and treatment.
      However, the interaction between them has not been studied. METHODS: The impact
      of ER over-expression or down-expression by DNA/small interfering RNA (siRNA)
      transfection, ERalpha agonists, and the ERbeta agonist diarylpropiolnitrile (DPN)
      on PPARgamma expression/activity was examined in papillary thyroid carcinoma
      (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARgamma
      modulation by rosiglitazone (RTZ), a PPARgamma ligand, and of PPARgamma siRNA on
      ER expression were determined. Cellular functions reflected by cell proliferation
      and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated
      by Western blot analysis. RESULTS: PPARgamma protein and activity were reduced by
      the over-expression of either ERalpha or ERbeta, whereas repression of ERalpha or
      ERbeta increased PPARgamma expression. The administration of RTZ counteracted the
      effects of ER and also reduced their expression, particularly in PTC cells.
      Moreover, knockdown of PPARgamma increased ER expression and activity.
      Functionally, ERalpha activation offset the inhibitory effect of PPARgamma on
      cellular functions, but ERbeta activation aggregated it and induced apoptosis,
      particularly in PTC cells. Finally, the interaction between ERbeta and PPARgamma
      enhanced the expression of proapoptotic molecules, such as caspase-3 and
      apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a
      cross-talk between ER and PPARgamma. The reciprocal interaction between PPARgamma
      and ERbeta significantly inhibits the proliferation and migration of thyroid
      cancer cells, providing a new therapeutic strategy against thyroid cancer.

PMID- 24114185
TI  - Soil biological attributes in arsenic-contaminated gold mining sites after
      revegetation.
AB  - Recovery of arsenic contaminated areas is a challenge society faces throughout
      the world. Revegetation associated with microbial activity can play an essential
      role in this process. This work investigated biological attributes in a gold
      mining area with different arsenic contents at different sites under two types of
      extant revegetation associated with cover layers of the soil: BS, Brachiaria sp.
      and Stizolobium sp., and LEGS, Acacia crassicarpa, A. holosericea, A. mangium,
      Sesbania virgata, Albizia lebbeck and Pseudosamanea guachapele. References were
      also evaluated, comprising the following three sites: B1, weathered sulfide
      substrate without revegetation; BM, barren material after gold extraction and
      PRNH (private reserve of natural heritage), an uncontaminated forest site near
      the mining area. The organic and microbial biomass carbon contents and substrate
      induced respiration rates for these sites from highest to lowest were: PRNH >
      LEGS > BS > B1 and BM. These attributes were negatively correlated with soluble
      and total arsenic concentration in the soil. The sites that have undergone
      revegetation (LEGS and BS) had higher densities of bacteria, fungi, phosphate
      solubilizers and ammonium oxidizers than the sites without vegetation. Principal
      component analysis showed that the LEGS site grouped with PRNH, indicating that
      the use of leguminous species associated with an uncontaminated soil cover layer
      contributed to the improvement of the biological attributes. With the exception
      of acid phosphatase, all the biological attributes were indicators of soil
      recovery, particularly the following: microbial carbon, substrate-induced
      respiration, density of culturable bacteria, fungi and actinobacteria, phosphate
      solubilizers and metabolic quotient.

PMID- 24114186
TI  - Toxicological aspects of injectable gold-hyaluronan combination as a treatment
      for neuroinflammation.
AB  - Secondary inflammatory reactions to stroke or trauma contribute to irreplaceable
      loss of brain tissue of the affected patients. Likewise, neuroinflammatory
      processes are the main pathophysiological feature in Multiple Sclerosis (MS), a
      common neurodegenerative disease among young adults. In the search for safe and
      efficient ways to reduce inflammation within nervous tissue older
      immunosuppressive remedies have been re-investigated. The anti-inflammatory
      properties of gold salts are well known but result in uncontrollable systemic
      spread of gold ions, generating side effects such as nephrotoxicity, limiting
      their use. Recent studies have circumvented this obstacle by introducing metallic
      gold implants as a localized source of immune-modulating gold ions and suspension
      in hyaluronic acid (HA) enables injection of small amounts of gold in the natural
      spaces of the brain. By injecting >25 MUm gold beads in HA intracerebrally we
      recently showed a slowing of disease progression in a rodent model of MS. The
      toxicological aspects were, however, not assessed. The present study investigates
      the viability of neuronal and macrophage cell cultures exposed to the gold/HA
      combination and the possible risk associated with unilateral gold/HA injection in
      young Balb/CA mice in the first 7 to 21 days of gold-exposure. Tracing by
      autometallography of gold accumulations throughout the brain exhibited sparse
      gold uptake in glia and neurons of hippocampus and cortex, and striatum and
      cerebellum were void of staining. No systemic spread of gold was seen in liver or
      kidney, nor were there signs of obstruction of the ventricular system. Both cell
      cultures of J774 macrophages and CCL neurons accumulated gold from gold/HA
      exposure with no signs of reduced viability. In conclusion, our findings indicate
      that gold/HA is not overtly neuro- or cytotoxic, nor does intraventricular
      exposure result in widespread gold accumulation or tissue damage, warranting
      further studies into the pharmacological properties of this novel form of gold
      treatment.

PMID- 24114187
TI  - Functional imaging to predict tumor response in locally advanced cervical cancer.
AB  - Worldwide, cervical cancer is the third commonest cancer. Prognostic factors for
      cervical cancer include tumor size, histological subtype, histological grade,
      International Federation of Gynecology and Obstetrics (FIGO) stage, nodal status
      and performance status. However these known parameters are not sufficient to
      accurately predict treatment response or prognosis. There is a clinical need for
      noninvasive prognostic biomarkers to provide more detailed tumor characterization
      at the baseline and/or early during therapy, which may permit personalized
      treatment and potentially improve outcomes. Functional imaging techniques have
      been developing rapidly over the past decade. Imaging parameters derived from
      PET/CT and functional MRI techniques are emerging as promising response
      biomarkers. This review details the current evidence and future potential of
      functional imaging to predict tumor response in locally advanced cervical
      carcinoma. 

PMID- 24114188
TI  - Clear cell carcinoma of ovary and uterus.
AB  - Clear cell carcinomas of the female genital tract are rare tumours with a
      fearsome reputation for having poor responses to conventional platinum-based
      chemotherapy and poor prognosis. However, it is now clear that early-stage
      ovarian clear cell carcinoma has an excellent prognosis and may not require any
      adjuvant therapy. In addition, radiotherapy may also have a key role to play in
      adjuvant management of clear cell tumours. Identification of patients who truly
      do not need adjuvant chemotherapy is important. The past 3 years has seen a
      significant improvement in our understanding of clear cell carcinoma biology-in
      particular, the role of mutations in the chromatin remodelling gene ARID1A as key
      drivers that are common to clear cell carcinomas of ovarian and endometrial
      origin. Moreover, gynaecological clear cell carcinomas appear to share many
      features with renal clear cell tumours, suggesting a common pathogenesis. This
      raises the possibility of clinical trials that include patients with clear cell
      tumours from different organs of origin. Dissecting the role of disordered
      chromatin organisation in clear cell carcinoma pathogenesis is a key priority.
      Finally, the role of endometriosis and the attendant chronic inflammation are
      recognised. The inflammatory cytokine interleukin-6 appears to play a key role in
      clear cell carcinoma biology and is an excellent potential therapeutic target.

PMID- 24114192
TI  - Mycobacterial pseudotumor of the skin.
AB  - Inflammatory pseudotumors have a diverse etiology, mycobacterial pseudotumor (MP)
      being one of them. MP is a rare entity; it has been reported infrequently in
      various organs and is extremely rare in the skin. We report a cutaneous MP in an
      immunosuppressed liver transplant recipient. The lesion consisted mostly of
      spindle cells, with small numbers of lymphocytes. Conventional acid-fast bacilli
      (AFB) stain revealed a large number of acid-fast bacilli within spindled
      histiocytes and the presence of Mycobacterium avium was determined by polymerase
      chain reaction. Given that the patient had a prior history of cutaneous squamous
      cell carcinoma resected and reconstructed in the same area, establishing the
      diagnosis was challenging. Immunohistochemical staining for lysosome-associated
      membrane protein was strongly positive, suggesting the presence of numerous
      mature lysosomes within infected spindle cells. Mycobacterial spindle cell
      pseudotumors can mimic malignant or benign neoplasms and should be considered in
      differential diagnosis of spindle cell lesions, especially in immunocompromised
      patients. Further studies are needed to determine mechanisms that permit the
      survival of mycobacteria within the lesions and that cause this unusual
      manifestation of infection.

PMID- 24114189
TI  - Role of aspirin in cancer prevention.
AB  - Since its first synthesis in 1897, several medicinal roles and mechanisms of
      action of aspirin have become apparent; the latest among these being its role in
      cancer prevention and treatment. A large body of evidence supports aspirin's
      effect in reducing cancer incidence and cancer mortality, but duration of use
      needs to be at least 5 years. The beneficial effects are particularly large for
      colorectal, oesophageal and gastric cancers, with apparently smaller reductions
      for breast, prostate and lung cancer. The major harm is gastrointestinal
      bleeding, but serious sequelae are minimal at ages <70 years. It is very likely
      that use of prophylactic aspirin in the general population aged 50-70+ years will
      result in net overall benefit. Outstanding issues are: whether standard dose
      (~300 mg/day) can lead to greater net benefits than low dose (75-100 mg/day), the
      optimum duration of use, and appropriate ages for use in average-risk
      individuals.

PMID- 24114193
TI  - Current sickle cell disease management practices in Nigeria.
AB  - BACKGROUND: Although Nigeria has the highest burden of sickle cell disease (SCD)
      worldwide, there is still variable and poor utilisation of standard-of-care
      practices for SCD patients in the country. METHODS: This was a questionnaire
      survey of doctors in some dedicated SCD clinics in Nigeria in order to document
      the facilities available and common management practices. RESULTS: There were
      responses from 18 clinics based in 11 institutions. The number of patients being
      followed in each centre ranged from 15 to approximately 11 000. All clinics
      provided malaria prophylaxis and folic acid routinely to their patients. Only
      eight clinics prescribe penicillin prophylaxis. Eight prescribe hydroxyurea to
      patients who can afford it when indicated. All of the centres except three have
      electronic cell counters, but all had access to haemoglobin electrophoresis.
      Three had high-performance liquid chromatography machines installed but none was
      being routinely used. One institution had a functioning molecular biology
      laboratory. There is no official newborn screening programme in the country. All
      had access to microbiology and chemistry laboratories. Nine institutions had CT,
      six had MRI and three had transcranial Doppler facilities. CONCLUSION: The care
      available for SCD in Nigeria is still suboptimal and there is an urgent need for
      concerted effort to tackle the problem, but to make a significant impact on the
      burden of the disease would require more focus at the primary care level. Some
      steps to achieving this are outlined.

PMID- 24114194
TI  - Effects of novel cathepsin K inhibitor ONO-5334 on bone resorption markers: a
      study of four sustained release formulations with different pharmacokinetic
      patterns.
AB  - The purpose of the study was clarify the effect of the cathepsin K inhibitor ONO
      5334 on bone resortion markers using sustained release (SR) formulations with
      different pharmacokinetic (PK) patterns, and identify the optimal SR formulation.
      The PK profiles and pharmacodynamic effect on bone resorption markers of 4 SR
      candidates formulations were evaluated in healthy postmenopausal women within a
      randomized, 2-part, open-label crossover study. In Part A, subject received a
      single dose of each formulation orally in the fed state. In Part B, two selected
      formulations were evaluated in the fasted state. From the results from Part A,
      C(max) was reduced and plasma concentrations of ONO-5334 were sustained with all
      SR formulations compared with an immediate release tablet. In pharmacodynamics,
      the level of C-terminal telopeptide of type I collagen (CTX) in serum and urine
      were inhibited with SR tablets rather than with granules. C max and area under
      the concentration-time curve from time 0 to the last measurable time point (AUC(0
      t)) of SR tablets were higher than those of granules. From Part B, C max in the
      fasted condition was lower than that in the fed condition with two SR tablets. In
      contrast, C(24 h) in the fasted condition was slightly higher than that in the
      fed condition, but AUC(0-t) was similar. The inhibitory effect on CTX in serum
      and urine may depend on the PK pattern of ONO-5334. The SR tablets was well
      tolerated in postmenopausal women and has the optimal SR profiles on
      pharmacodynamics effect on bone resortion markers and PK profile. These results
      suggest that SR tablets of ONO-5334 are an excellent drug candidate for
      osteoporosis.

PMID- 24114195
TI  - Low level irradiation in mice can lead to enhanced trabecular bone morphology.
AB  - Charged particle radiation such as iron ions and their secondary fragmentation
      products are of particular concern to the skeleton due to their high charge and
      energy deposition. However, little is known about the long-term effects of these
      particles on trabecular and cortical bone morphology when applied at relatively
      low levels. We hypothesized that even a 4.4 cGy dose of a complex secondary iron
      ion radiation field will compromise skeletal quantity and architecture in adult
      mice. One year after radiation exposure and compared to age-matched controls, 4.4
      cGy irradiated mice had 51 % more trabecular bone, 56 % greater trabecular bone
      volume fraction, 16 % greater trabecular number, and 17 % less trabecular
      separation in the distal metaphysis of the femur. Similar to the metaphysis,
      trabecular bone of the distal femoral epiphysis in 4.4 cGy mice had 33 % more
      trabecular bone, 31 % greater trabecular bone volume fraction, and a 33 % smaller
      structural model index. Cortical bone morphology, whole bone mechanical
      properties, and lower leg muscle mass were unaffected. When compared to two
      additional groups, irradiated at either 8.9 or 17.8 cGy, a (negative) dose
      response relationship was observed for trabecular bone in the metaphysis but not
      in the epiphysis. In contrast to our original hypothesis, these data indicated
      that a secondary field of low-level, high-linear energy transfer iron radiation
      may cause long-term augmentation, rather than deterioration, of trabecular bone
      in the femoral metaphysis and epiphysis of mice.

PMID- 24114196
TI  - Is the negative relationship between obesity and bone mineral content greater for
      older women?
AB  - Obesity and osteoporosis are two important body composition problems with
      increasing prevalences in aged populations. Traditionally, obesity has been
      regarded as being beneficial to bone health. However, the protective effect of
      obesity on osteoporosis has been questioned. In some recent studies, obesity, as
      defined by percentage body fat, was regarded as a risk factor for osteoporosis.
      The purpose of this study was to (1) evaluate the effect of waist circumference,
      a surrogate measure for abdominal obesity, on bone mineral content (BMC) and (2)
      examine whether the effect of waist circumference increases with advancing age.
      The study population is made up of women aged over 45 years who completed the
      body composition and bone mineral density examinations in the fifth Korea
      National Health and Nutrition Examination Survey in 2010. Subjects who take
      estrogen or are under medical treatment for osteoporosis were excluded. Stroke
      patients are also excluded. Femoral neck, total-hip, and whole-body BMC were
      measured by dual-energy X-ray absorptiometry. A total of 1,434 subjects were
      included in the analysis. Waist circumference was negatively associated with BMC
      in all tested regions after correction for weight, menopausal status, smoking,
      drinking, and exercise. In addition, the negative association between waist
      circumference and BMC in the femoral neck and total hip increases with age, after
      correction for confounding factors, showing an interaction effect between waist
      circumference and age on BMC. In conclusion, this study shows that the negative
      relationship between waist circumference and BMC in the femoral neck and total
      hip is greater for older women.

PMID- 24114197
TI  - Utility of p40 in the Differential Diagnosis of Small Round Blue Cell Tumors of
      the Sinonasal Tract.
AB  - The sinonasal tract may give rise to a broad range of neoplasms that share a
      "small round blue cell" tumor (SBRCT) appearance on routine histology, but
      treatment strategies depend on precise tumor classification. Immunohistochemistry
      for p63 is often employed in the sinonasal SRBCT differential diagnosis because
      it is highly sensitive for squamous cell carcinoma (SCC). However, p63 staining
      may be observed in other tumor types, a potential diagnostic pitfall. P40 is a
      more squamous-specific isoform of p63, and it may be more useful in
      distinguishing poorly differentiated SCC from its mimickers in the sinonasal
      tract. Immunohistochemistry for p40 and p63 was performed on 171 sinonasal
      neoplasms with SRBCT morphology: 73 SCCs (67 poorly differentiated, non
      keratinizing, or basaloid types and 6 nasopharyngeal carcinomas), 46
      esthesioneuroblastomas, 11 sinonasal undifferentiated carcinomas (SNUCs), 11
      lymphomas, 9 melanomas, 7 alveolar rhabdomyosarcomas, 4 solid adenoid cystic
      carcinomas, 4 NUT midline carcinomas, 4 primitive neuroectodermal tumors (PNETs),
      and 2 small cell carcinomas. P40 was positive in 72 of 73 SCCs, and showed a
      diffuse distribution in all but one positive case. P40 immunoexpression was also
      observed in 13 of 46 (28 %) esthesioneuroblastomas, 6 of 11 (55 %) SNUCs, 2 of 4
      (50 %) adenoid cystic carcinomas, 3 of 4 (75 %) NUT midline carcinomas, 1 of 2
      (50 %) small cell carcinomas, and 1 of 4 (25 %) PNETs; in the non-SCC tumors, p40
      staining was focal in most cases. P63 was positive in every p40-positive tumor.
      In addition, a p63+/p40- phenotype was seen 5 of 11 (45 %) lymphomas, 4 of 7 (57
      %) alveolar rhabdomyosarcomas, 1 of 4 (25 %) PNETs, and 3 of 46 (7 %)
      esthesioneuroblastomas. All sinonasal melanomas were negative for both markers.
      In the sinonasal SRBCT differential diagnosis, both p40 and p63 are highly
      sensitive for SCC, but p40 is more specific. Notably, p40 is consistently
      negative in lymphomas and alveolar rhabdomyosarcomas, two tumors that are
      frequently p63-positive. It must be remembered, however, that even diffuse p40
      immunostaining is not entirely specific for the squamous phenotype, and therefore
      it should be utilized as part of an immunohistochemical panel. 

PMID- 24114198
TI  - miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral
      cancer by silencing neuropilin 1.
AB  - Tumor angiogenesis is a critical process during cancer progression that modulates
      tumor growth and metastasis. Here, we identified an anti-angiogenic microRNA, miR
      320, which is decreased in oral squamous cell carcinoma (OSCC) cell lines and
      tumor tissues from OSCC patients, down-regulated in blood vessels and inversely
      correlated with vascularity in OSCC tissues. Neuropilin 1 (NRP1), an important
      regulator of angiogenesis, was found to be a target of miR-320. The 3'
      untranslated region of NRP1 mRNA contains multiple miR-320 binding sites, and its
      expression was regulated by miR-320. By administering either miR-320 precursor or
      antagonist, we found that miR-320 suppressed the migration, adhesion and tube
      formation of vascular endothelial cells. Knockdown of NRP1 abolished antagomiR
      320-induced cell migration. Additionally, miR-320 expression was regulated by
      hypoxia in growth factor-deficient conditions by the hypoxia-inducible factor 1
      alpha. Furthermore, lentivirus carrying the miR-320 precursor suppressed the
      tumorigenicity of OSCC cells and tumor angiogenesis in vivo. Taken together,
      these data show that miR-320 regulates the function of vascular endothelial cells
      by targeting NRP1 and has the potential to be developed as an anti-angiogenic or
      anti-cancer drug. 

PMID- 24114200
TI  - VEGFA gene locus analysis across 80 human tumour types reveals gene amplification
      in several neoplastic entities.
AB  - BACKGROUND: Angiogenesis plays a pivotal role in neoplastic growth and metastasis
      formation. Vascular endothelial growth factor A (VEGFA) is a major player in
      physiological and tumour-induced angiogenesis and numerous human tumours have
      been show to overexpress VEGFA. Moreover increased VEGFA gene expression has been
      found frequently to correlate with tumour progression, recurrences and survival.
      Interestingly, several studies have demonstrated that gene amplification may
      result in protein overexpression and that amplification of the therapeutics'
      target gene can serve as an excellent predictive marker (i.e. HER2 and
      trastuzumab). However the impact of VEGFA gene amplification has been only
      recently assessed for some cancer types such as osteosarcoma, colorectal, breast
      and liver cancer. AIMS: This study aimed to assess VEGFA gene amplification
      status using fluorescent in situ hybridization (FISH) in a large cohort of
      different tumour entities. Thus, we investigated the incidence of VEGFA
      amplification using a multi-tumour tissue microarray (TMA) containing 2,837
      evaluable specimens from 80 different tumour entities and 31 normal tissue types.
      Moreover, we validated FISH analysis as reference method to evaluate VEGFA gene
      status by comparing it to comparative genomic hybridization (CGH). RESULTS: We
      observed that VEGFA locus amplification and/or polysomy represented a small but
      regularly detected population in several tumour entities while was not present in
      normal tissues. VEGFA gene alterations were predominantly observed in
      hepatocarcinomas, adenocarcinomas of the pancreas and intestine, large cell
      carcinoma of the lung and in endometrium serous carcinoma. Furthermore our data
      demonstrated that VEGFA detection by FISH provided highly comparable results to
      those generated by CGH. CONCLUSION: Albeit with low percentage, VEGFA
      amplification is commonly observed across several tumour entities. Furthermore,
      our results demonstrated that FISH test could be used as a reliable diagnostic
      tool to evaluate VEGFA gene status in human specimens.

PMID- 24114199
TI  - The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates
      vascular permeability through endothelial production of PDGF-B and ANGPTL4.
AB  - Semaphorin 4D (SEMA4D) is a member of a family of transmembrane and secreted
      proteins that have been shown to act through its receptor Plexin-B1 to regulate
      axon growth cone guidance, lymphocyte activation, and bone density. SEMA4D is
      also overexpressed by some malignancies and plays a role in tumor-induced
      angiogenesis similar to vascular endothelial growth factor (VEGF), a protein that
      has been targeted as part of some cancer therapies. In an attempt to examine the
      different effects on tumor growth and vascularity for these two pro-angiogenic
      factors, we previously noted that while inhibition of both VEGF and SEMA4D
      restricted tumor vascularity and size, vessels forming under conditions of VEGF
      blockade retained their association with pericytes while those arising in a
      background of SEMA4D/Plexin-B1 deficiency did not, an intriguing finding
      considering that alteration in pericyte association with endothelial cells is an
      emerging aspect of anti-angiogenic intervention in the treatment of cancer. Here
      we show through array analysis, immunoblots, migration and co-culture assays and
      VE-cadherin immunohistochemistry that SEMA4D production by head and neck
      carcinoma tumor cells induces expression of platelet-derived growth factor-B and
      angiopoietin-like protein 4 from endothelial cells in a Plexin-B1/Rho-dependent
      manner, thereby influencing proliferation and differentiation of pericytes and
      vascular permeability, whereas VEGF lacks these effects. These results partly
      explain the differences observed between SEMA4D and VEGF in pathological
      angiogenesis and suggest that targeting SEMA4D function along with VEGF could
      represent a novel anti-angiogenic therapeutic strategy for the treatment of solid
      tumors. 

PMID- 24114203
TI  - Facilitated charge transport in ternary interconnected electrodes for flexible
      supercapacitors with excellent power characteristics.
AB  - Flexible and high performance supercapacitors are very critical in modern
      society. In order to develop the flexible supercapacitors with high power
      density, free-standing and flexible three-dimensional graphene/carbon
      nanotubes/MnO2 (3DG/CNTs/MnO2) composite electrodes with interconnected ternary
      3D structures were fabricated, and the fast electron and ion transport channels
      were effectively constructed in the rationally designed electrodes. Consequently,
      the obtained 3DG/CNTs/MnO2 composite electrodes exhibit superior specific
      capacitance and rate capability compared to 3DG/MnO2 electrodes. Furthermore, the
      3DG/CNTs/MnO2 based asymmetric supercapacitor demonstrates the maximum energy and
      power densities of 33.71 W h kg(-1) and up to 22,727.3 W kg(-1), respectively.
      Moreover, the asymmetric supercapacitor exhibits excellent cycling stability with
      95.3% of the specific capacitance maintained after 1000 cycle tests. Our proposed
      synthesis strategy to construct the novel ternary 3D structured electrodes can be
      efficiently applied to other high performance energy storage/conversion systems.

PMID- 24114202
TI  - Meta - and combined - QTL analysis of different experiments on immune traits in
      chickens.
AB  - Meta and/or combined QTL analysis from multiple studies can improve quantitative
      trait loci (QTL) position estimates compared to the individual experiments.
      Hereby we present results of a meta-analysis of QTL on chicken chromosome 9, 14
      and 18 using data from three separate experiments and joint QTL analysis for
      chromosome 14 and 18. Meta QTL analysis uses information from multiple QTLs
      studies. Joint QTL analysis is based on combining raw data from different QTL
      experimental populations. QTLs under the study were related to specific antibody
      response to keyhole lymphet hemocyanin (KLH), and natural antibodies to
      environmental antigens, lipopolisaccharide (LPS) and lipoteichoic acid (LTA).
      Meta QTL analysis resulted in narrowing down the confidence interval for two QTLs
      on GGA14. The first one for natural antibodies against LTA and the second one for
      specific antibody response toward KLH. Also, a confidence interval of a QTL for
      natural antibodies against LPS located on GGA18 was narrowed down. Combined QTL
      analysis was successful for two QTLs: for specific antibody response toward KLH
      on GGA14, and for natural antibodies against LPS on GGA18. The greatest
      statistical power for QTL detection in joint analysis was achieved when raw data
      from segregating half-sib families from different populations under the study was
      used. 

PMID- 24114201
TI  - LXRalpha gene expression, genetic variation and association analysis between
      novel SNPs and growth traits in Chinese native cattle.
AB  - Liver X receptor alpha (LXRalpha) has emerged as an important regulator of lipid
      and energy metabolism. In this study, to better understand the effects of
      LXRalpha gene on growth traits in cattle, the mRNA tissue expression patterns and
      the polymorphisms of some exons of LXRalpha were revealed. The expression profile
      of the bovine LXRalpha gene was detected by quantitative real-time polymerase
      chain reaction (qRT-PCR) in 11 different Jiaxian cattle tissues and was found
      mainly expressed in spleen, liver, fat tissue, kidney, muscle, and lung.
      Meanwhile, it showed that four single nucleotide polymorphisms (SNPs), named
      g.1028 T>C, g.1514 T>C, g.2929G>A, and g.3493 T>C, were detected and 12 different
      haplotypes were constructed. Haplotype with CCGT was dominant with frequency of
      40.8 %. There was a strong link between g.1028 T>C and g.1514 T>C (r (2) =
      0.374). Association analysis of SNPs with growth- and body-related traits was
      carried out in 445 Chinese native cattle. The results displayed that the
      heterozygous genotypes of g.1028 T>C and g.1514 T>C showed a molecular heterosis
      on four performance traits related to body size: height at withers, body length,
      hipbone width, and hip width (P < 0.05). The multiple effects of four sites
      showed that the height at withers, body length, hipbone width, and hip width of
      individuals of TC-TC-GG-TT combined genotypes were significantly higher than
      other genotypes (P < 0.05). The effects of the four loci genotype combination on
      conformation traits were consistent with the effects of g.1028 T>C and g.1514 T>C
      loci. The SNPs of g.1028 T>C and g.1514 T>C of the bovine LXRalpha gene could be
      potential genetic markers for growth traits in cattle. These results suggest that
      LXRalpha gene is expressed in many tissues and may provide primary molecular
      information for further studies on body size traits in Chinese indigenous cattle.

PMID- 24114205
TI  - CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in
      mice.
AB  - The chemokine receptor CCR6 is expressed by various cell subsets implicated in
      atherogenesis, such as monocytes, Th17 and regulatory T cells. In order to
      further define the role of CCR6 in atherosclerosis, CCR6-deficient (Ccr6-/-) mice
      were crossed with low-density lipoprotein receptor-deficient (Ldlr-/-) mice to
      generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldlr-/-
      controls, atherosclerotic burden in the aortic sinus and aorta were reduced in
      Ccr6-/-Ldlr-/- mice fed a high fat diet, associated with a profound depression in
      lesional macrophage accumulation. Local and systemic distributions of T cells,
      including frequencies of Th1, Th17 and regulatory T cells were unaltered. In
      contrast, circulating counts of both Gr-1(high) and Gr1(low) monocytes were
      reduced in Ccr6-/-Ldlr-/- mice. Moreover, CCR6 was revealed to promote monocyte
      adhesion to inflamed endothelium in vitro and leukocyte adhesion to carotid
      arteries in vivo. Finally, CCR6 selectively recruited monocytes but not T cells
      in an acute inflammatory air pouch model. We here show that CCR6 functions on
      multiple levels and regulates the mobilisation, adhesion and recruitment of
      monocytes/macrophages to the inflamed vessel, thereby promoting atherosclerosis,
      but is dispensable for hypercholesterolaemia-associated adaptive immune priming.
      Targeting CCR6 or its ligand CCL20 may therefore be a promising therapeutic
      strategy to alleviate atherosclerosis.

PMID- 24114206
TI  - Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a
      gastric adenocarcinoma cell line (PG100).
AB  - There is a constant search for new cancer treatments that are less aggressive and
      economically affordable. In this context, natural products extracted from plants,
      fungi, and microorganisms are of great interest. Pestheic acid, or
      dihidromaldoxin, is a chlorinated diphenylic ether extracted from the
      phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed
      the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric
      adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed.
      Pestheic acid also induced significant increases in both micronucleus and
      nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle
      kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic
      ethers may explain the genotoxicity and mutagenicity of pestheic acid. The
      absence of repair checkpoints that we observed is probably due to the fact that
      the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even
      though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory
      concentration was high, which shows that pestheic acid is not an active
      anticancer compound under these conditions. 

PMID- 24114207
TI  - Molecular cloning, sequence characterization, and gene expression profiling of a
      novel water buffalo (Bubalus bubalis) gene, AGPAT6.
AB  - Several 1-acylglycerol-3-phosphate-O-acyltransferases (AGPATs) can acylate
      lysophosphatidic acid to produce phosphatidic acid. Of the eight AGPAT isoforms,
      AGPAT6 is a crucial enzyme for glycerolipids and triacylglycerol biosynthesis in
      some mammalian tissues. We amplified and identified the complete coding sequence
      (CDS) of the water buffalo AGPAT6 gene by using the reverse transcription
      polymerase chain reaction, based on the conversed sequence information of the
      cattle or expressed sequence tags of other Bovidae species. This novel gene was
      deposited in the NCBI database (accession No. JX518941). Sequence analysis
      revealed that the CDS of this AGPAT6 encodes a 456-amino acid enzyme (molecular
      mass = 52 kDa; pI = 9.34). Water buffalo AGPAT6 contains three hydrophobic
      transmembrane regions and a signal 37-amino acid peptide, localized in the
      cytoplasm. The deduced amino acid sequences share 99, 98, 98, 97, 98, 98, 97 and
      95% identity with their homologous sequences from cattle, horse, human, mouse,
      orangutan, pig, rat, and chicken, respectively. The phylogenetic tree analysis
      based on the AGPAT6 CDS showed that water buffalo has a closer genetic
      relationship with cattle than with other species. Tissue expression profile
      analysis shows that this gene is highly expressed in the mammary gland,
      moderately expressed in the heart, muscle, liver, and brain; weakly expressed in
      the pituitary gland, spleen, and lung; and almost silently expressed in the small
      intestine, skin, kidney, and adipose tissues. Four predicted microRNA target
      sites are found in the water buffalo AGPAT6 CDS. These results will establish a
      foundation for further insights into this novel water buffalo gene. 

PMID- 24114208
TI  - Correlation of growth-related traits and their effects on body weight of the mud
      crab (Scylla paramamosain).
AB  - In this study, we analyzed the correlation of 20 growth-related traits and their
      effects on body weight of Scylla paramamosain. The correlation coefficients in
      all trait pairs were significantly high, ranging from 0.551 to 0.999. Among 19 X
      Y pairs, the correlation coefficient between traits X1 and Y was the highest,
      whereas that between X13 and Y was the lowest. Path analysis indicated that only
      two traits (X1 and X14) can significantly affect body weight (Y) directly, with
      the path coefficients being 0.800 and 0.198, respectively. The determination
      coefficients (di) of traits X1 and X14 to body weight were 0.640 and 0.039,
      respectively, and the total di was 0.965, indicating that both traits were the
      key factors affecting body weight. Moreover, traits X1 and X14 were confirmed to
      be significantly related to body weight. Finally, a best-fit linear regression
      equation was constructed as Y = 4.192X1 + 2.242X14 - 169.737. 

PMID- 24114210
TI  - Molecular characterization of the pseudorabies virus UL2 gene.
AB  - A 948-bp sequence of the UL2 gene was amplified from the pseudorabies virus (PRV)
      Becker strain genome using polymerase chain reaction, and the gene identity was
      confirmed through further cloning and sequencing. Bioinformatic analysis
      indicated that the PRV UL2 gene encodes a putative polypeptide with 315-amino
      acid residues. Its encoding protein, designated UL2, has a conserved uracil-DNA
      glycosylase (UDG)_F1 domain, which is closely related to the herpesvirus UDG
      family and is highly conserved among its counterparts encoded by UDG genes.
      Multiple nucleic acid and amino acid sequence alignments suggested that the
      product of PRV UL2 has a relatively higher homology with UL2-like proteins of
      Alphaherpesvirinae than that of other subfamilies of Herpesviridae. In addition,
      phylogenetic analysis showed that PRV UL2 had a close evolutionary relationship
      with members of Alphaherpesvirinae, especially members of the genus
      Varicellovirus of bovine herpesvirus 1 and bovine herpesvirus 5. Antigen
      prediction indicated the presence of several potential B-cell epitopes in PRV
      UL2. In addition, secondary structure and 3-dimensional structure prediction
      revealed that PRV UL2 consisted predominantly of an alpha-helix. Taken together,
      these results provide molecular biological insight for the further study of the
      function and mechanism of UL2 during PRV infection. 

PMID- 24114209
TI  - Effect of the Jianpi Bushen Prescription on expressions of the Wnt3a and Cyclin
      D1 genes in radiation-damaged mice.
AB  - The effects of the traditional Chinese drug Jianpi Bushen Prescription (JBP) were
      investigated on expressions of Wnt3a and Cyclin D1 genes in radiation-damaged
      mice. The radiation damage model was induced in Kumming mice by single total body
      irradiation treatment for 9 days. Mice were divided into the radiation group, low
      dose (100%) JBP group, high-dose (200%) JBP group, or batyl alcohol group
      (positive control), which were administered twice a day for 9 days. mRNA and
      protein expressions of Wnt3a were detected in bone marrow mononuclear cells by
      real-time polymerase chain reaction and Western blot, whereas Cyclin D1 mRNA was
      detected by in situ hybridization. Wnt3a expressions were significantly
      downregulated in the radiation damage model group compared with all other groups
      (P < 0.05). The positive cell rate of Cyclin D1 mRNA expression and the number of
      granulocyte macrophage colonies were significantly decreased in the radiation
      damage model group relative to all other groups (P < 0.05). Furthermore, mRNA and
      protein expressions of Wnt3a, the positive cell rate of Cyclin D1 mRNA expression
      in bone marrow cells, and the number of granulocyte macrophage colonies were all
      significantly higher in the low-dose JBP group than in the high-dose JBP group (P
      < 0.05). In summary, JBP plays a protective role on radiation-induced bone marrow
      through the activation of the Wnt3a signaling pathway, and promotes the
      transcription and expression of Cyclin D1. 

PMID- 24114211
TI  - Expression profiling analysis of hypoxic pulmonary disease.
AB  - Exposure of humans to low levels of environmental oxygen results in alveolar
      hypoxia and normally causes chronic pulmonary hypertension and morphological
      alterations of precapillary pulmonary vessels. In this study, the microarray
      dataset GSE11341 was used to identify potential differentially expressed genes
      related with human lung microvascular endothelial cell hypoxia. In addition, gene
      ontology term enrichment analysis was performed to explore their underlying
      functions. In addition, we also investigated the small molecules by comparing
      with the Connectivity Map. We found that hypoxia samples of 3, 24, and 48 h
      relative to 0 h displayed 22, 21, and 29 differentially expressed genes,
      respectively. Among them, six genes (ADM, HMOX1, VEGFA, EGLN3, APOLD1, and
      ANGPTL4) were closely related to pulmonary microvascular endothelial cell hypoxia
      response. Three drugs (pindolol, sulfapyridine, and ciclopirox) were selected as
      candidates to treat hypoxia-related pulmonary diseases. In conclusion, our
      results provide some underlying drug targets for treatment of hypoxic pulmonary
      patients. 

PMID- 24114212
TI  - Marker-assisted selection in breeding silkworm strains with high silk production
      and resistance to the densonucleosis virus.
AB  - In the silkworm (Bombyx mori), resistance to the Zhenjiang (China) strain of the
      densonucleosis virus (DNV-Z) is controlled by the recessive gene nsd-Z (non
      susceptible to DNV-Z), which is linked to 7 simple-sequence repeat markers.
      Marker-assisted evaluation and selection of DNV-Z-resistant silkworms were used
      for predicting DNV-resistance in backcrossed animals. A silkworm race was bred
      using this method, and its economic characteristics were found to be similar to
      those of commercial silkworm races. These markers will therefore be useful for
      silkworm breeding programs and in screening for densonucleosis resistance in
      segregating populations. 

PMID- 24114213
TI  - Molecular cloning and expression analysis of the ethylene insensitive3 (EIN3)
      gene in cucumber (Cucumis sativus).
AB  - The plant gaseous hormone ethylene regulates many aspects of plant growth,
      development, and responses to the environment. Ethylene insensitive3 (EIN3) is a
      key transcription factor involved in the ethylene signal transduction pathway. To
      gain a better understanding of this particular pathway in cucumber, the full
      length cDNA encoding EIN3 (designated as CsEIN3) was cloned from cucumber for the
      first time by rapid amplification of cDNA ends. The full length of CsEIN3 was
      2560 bp, with an open reading frame of 1908 bp encoding 635 amino acids. Sequence
      alignment and phylogenetic analyses revealed that CsEIN3 has high homology with
      other plant EIN3/EIL proteins that were derived from a common ancestor during
      evolution, and CsEIN3 was grouped into a cluster along with melon. Homology
      modeling demonstrated that CsEIN3 has a highly similar structure to the specific
      DNA-binding domain contained in EIN3/EIL proteins. Based on quantitative reverse
      transcription-polymerase chain reaction analysis, we found that CsEIN3 was
      constitutively expressed in all organs examined, and was increased during flower
      development and maturation in both male and female flowers. Our results suggest
      that CsEIN3 is involved in processes of flower development. In conclusion, this
      study will provide the basis for further study on the role of EIN3 in relevant
      biological processes of cucumber and on the molecular mechanism of the cucumber
      ethylene signaling pathway. 

PMID- 24114215
TI  - Expressions of Src homology 2 domain-containing phosphatase and its clinical
      significance in laryngeal carcinoma.
AB  - We investigated the expression of Src homology 2 domain-containing phosphatase
      (SHP-2) in laryngeal carcinoma and its clinical significance. Expression of SHP-2
      was detected by immunohistochemical staining in normal mucosal tissues and
      various grades of laryngeal carcinoma. We looked for possible correlations
      between expression of SHP-2 in laryngeal carcinoma and clinical staging and lymph
      node metastasis. Immunochemical staining results revealed that the SHP-2
      expression was significantly higher (88.24%) in laryngeal carcinoma than in
      normal mucosal tissue (25%). Additionally, the expression of SHP-2 was
      significantly correlated with lymph node metastasis, but not with clinical stage
      and gender of patients with laryngeal carcinoma. Therefore, SHP-2 may be useful
      as a prognostic marker for laryngeal carcinoma and as a therapeutic target in
      laryngeal carcinoma treatment. 

PMID- 24114214
TI  - Differential expression of L-FABP and L-BABP between fat and lean chickens.
AB  - Liver fatty acid-binding protein (L-FABP) and liver bile acid-binding protein (L
      BABP), in the liver intra-cytoplasm of chicken, are members of the fatty acid
      binding protein subfamily. This study was designed to analyze and compare L-FABP
      and L-BABP expression levels between fat and lean lines in chicken liver tissue,
      and to determine the relationship between their expression and lipid metabolism.
      Real-time polymerase chain reaction (PCR) and Western blotting were used to
      detect the mRNA and protein expression in liver tissue between the lean and fat
      lines. Real-time PCR showed that L-FABP mRNA expression in fat male chickens was
      higher than that in lean male chickens at 2, 3, 4, 5, 6, and 10 weeks of age (P <
      0.05), and L-BABP mRNA expression in fat male chickens was higher than that in
      lean male chickens at 1, 2, 3, 4, 8, and 10 weeks of age (P < 0.05). Western
      blotting showed that the L-FABP protein expression in fat male chickens was
      higher than that in lean male chickens at 3, 5, 6, and 7 weeks of age (P < 0.05),
      and L-BABP protein expression in fat male chickens was higher than that in lean
      male chickens at 3, 4, 5, and 6 weeks of age (P < 0.05). These results suggested
      that chicken L-FABP and L-BABP affect abdominal fat deposition through
      differences in their expression level, and the possible mechanism is that a high
      expression level of L-FABP and L-BABP leads to a high lipogenesis rate and,
      ultimately, to lipid deposition. 

PMID- 24114216
TI  - Identification of UV-B-induced microRNAs in wheat.
AB  - MicroRNAs (miRNAs) play critical roles in post-transcriptional gene regulation
      and act as important endogenous regulators to various stressors. Ultraviolet-B
      (UV-B) radiation is a major factor influencing crop growth and development. In
      this study, we isolated a novel wheat miRNA, named Tae-miR6000, and confirmed its
      expression diversity after UV-B treatments. Additionally, using the Northern
      blotting technique, we found that six miRNAs were highly responsive to UV-B
      stress in wheat. Of these six miRNAs, miR159, miR167a, and miR171 were
      significantly upregulated, and the remaining three miRNAs were downregulated, at
      different time points after UV-B treatment. This result indicates that miRNAs may
      be involved in the regulation of targets after induction by UV-B stress.
      Furthermore, promoter analysis of the UV-B-responsive miRNA genes revealed some
      light-relevant cis-elements, such as the I-box and G-box. Taken together, the
      results of this study suggest that wheat miRNAs play important roles in the
      response to UV-B stress. 

PMID- 24114217
TI  - Relationship between serum neopterin levels and coronary heart disease.
AB  - The relationship between serum neopterin levels and coronary heart disease (CHD)
      was investigated. Eighty-six CHD patients were divided into an acute myocardial
      infarction (AMI) group (N = 21), an unstable angina pectoris (UAP) group (N =
      35), and a stable angina pectoris (SAP) group (N = 30), based on coronary
      angiography (CAG), 30 subjects without CHD served as the control group. Serum
      neopterin levels were determined by enzyme linked immunosorbent assay (ELISA),
      and relationships between neopterin and the severity of stenosis, stenosis
      number, and the stability of coronary artery were analyzed. Serum neopterin
      levels were higher in the AMI and UAP groups than in the SAP and control groups
      (P < 0.01), but no significant differences were observed between the AMI and UAP
      groups or between the SAP and control groups (P > 0.05). Mean serum neopterin
      levels were higher in the single, double, and three vessel lesion groups than in
      the control group (P < 0.05), whereas there were no significant differences among
      the lesion groups (P > 0.05). Serum levels of neopterin were significantly higher
      in the type II than in the type I or type III, plaque groups (P < 0.01), the
      incidence of type II plaque was significantly higher in the AMI and UAP groups
      compared to the SAP group (P < 0.01). Neopterin likely plays a role in the
      occurrence and development of athermanous plaque and can serve as a useful
      biomarker of vulnerable plaques. Immunoreaction may be involved in the
      pathophysiological process of CHD. 

PMID- 24114218
TI  - Production and identification of doubled haploids in tropical maize.
AB  - The production of maize doubled haploid (DH) lines is a technique commonly used
      by private companies, but not by Brazilian public institutions. Research on this
      technique is essential to develop and improve the production of DH lines grown
      under tropical conditions. We assessed the ability of a gynogenetic haploid
      inducer system to induce haploids in a tropical environment, assessed the
      induction rate of haploids identified using the R-navajo morphological marker,
      checked for interference from the generation of hybrid donors on haploid
      induction, measured the ability of flow cytometry, and simple sequence repeat
      marker techniques to identify doubled haploids. Seeds from the inducer Krasnodar
      Embryo Marker Synthetic (KEMS) line were sown in Ponta Grossa, PR, and Cravinhos,
      SP, and the plants were crossed to produce six hybrids and their F2 generations.
      The seeds were separated according to the R-navajo morphological marker indicator
      of haploidy (purple endosperm and white embryo) and germinated in a controlled
      environment. Chromosomal duplication was performed in seedlings selected as
      putative haploids. We performed subsequent confirmation of ploidy and the success
      of duplication using flow cytometry and SSR marker techniques. We concluded that
      DH lines can be obtained from hybrids crossed with the inducer KEMS line. The
      generation of inbred hybrids did not affect the induction rate or chromosomal
      duplication in haploids. The use of flow cytometry and SSR markers was effective
      in verifying chromosomal duplication in haploids. 

PMID- 24114219
TI  - Effects of peer mediation on preschoolers' compliance and compliance precursors.
AB  - We used a multiple baseline design across participants to evaluate the effects of
      teaching 4 typically developing preschoolers to attend to their names and to a
      group call (referred to as precursors) on their compliance with typical classroom
      instructions. We then measured the extent to which the effects on both precursors
      and compliance were maintained when the teaching procedures were removed. Levels
      of compliance eventually decreased for all children. A multiple baseline design
      across participants was then used to evaluate the effects of peer mediation on
      the maintenance of precursors and compliance. Peer mediation involved teaching
      the children to either remind one another to engage in a precursor or praise one
      another for engaging in a precursor. Compliance improved with all children as a
      function of teaching precursors, and these changes were maintained through the
      use of peer mediation. 

PMID- 24114220
TI  - Internet-based contingency management increases walking in sedentary adults.
AB  - Despite the link between inactivity and premature mortality, most adults exercise
      less than the Centers for Disease Control and Prevention (2008) recommends; thus,
      interventions to increase exercise are needed. The present study employed an
      Internet-based intervention to increase walking in 12 sedentary adults over 50
      years of age. In Experiment 1, participants received monetary consequences for
      meeting an increasing series of step goals on at least 3 days during consecutive
      5-day blocks. Across participants, steps increased 182% from screening to the end
      of the intervention, and 87% of step goals were met. In Experiment 2, goals were
      set using the same schedule as in Experiment 1, but no monetary consequences were
      provided for meeting them. Across participants, steps increased 108%, and 52% of
      goals were met. Across both studies, 11 of 12 participants increased their steps
      according to experimenter-arranged criteria. These results support the efficacy
      of an Internet-based intervention to increase walking in sedentary adults. 

PMID- 24114222
TI  - Peer presence and the emergence of conditioned reinforcement from observation.
AB  - We examined the effects of peer presence on the conditioning of new reinforcers
      via observation. At the outset, strings and toothpicks did not reinforce
      maintenance or acquisition responses for 3 preschoolers with and without
      developmental delays. In the first intervention, the stimuli were placed in a cup
      in front of an empty chair next to the participant, and the participant was
      denied access to those stimuli. The second intervention was identical to the
      first, except that a peer was present. Postintervention tests revealed that only
      the peer intervention was successful in conditioning neutral stimuli as
      reinforcers for both maintenance and acquisition responses for all 3
      participants. The presence of a peer appears to facilitate the conditioning of
      reinforcers by observation. 

PMID- 24114221
TI  - Monetary incentives to reinforce engagement and achievement in a job-skills
      training program for homeless, unemployed adults.
AB  - The current study examined whether monetary incentives could increase engagement
      and achievement in a job-skills training program for unemployed, homeless,
      alcohol-dependent adults. Participants (n=124) were randomized to a no
      reinforcement group (n=39), during which access to the training program was
      provided but no incentives were given; a training reinforcement group (n=42),
      during which incentives were contingent on attendance and performance; or an
      abstinence and training reinforcement group (n=43), during which incentives were
      contingent on attendance and performance, but access was granted only if
      participants demonstrated abstinence from alcohol. abstinence and training
      reinforcement and training reinforcement participants advanced further in
      training and attended more hours than no-reinforcement participants. Monetary
      incentives were effective in promoting engagement and achievement in a job-skills
      training program for individuals who often do not take advantage of training
      programs.

PMID- 24114223
TI  - Effects of alternative responses on behavior exposed to noncontingent
      reinforcement.
AB  - Noncontingent reinforcement (NCR) may decrease the frequency of behavior by
      either inducing satiation or terminating the response-reinforcer contingency
      (extinction). Another possibility is that the target behavior is replaced by
      other behaviors maintained by preexisting contingencies. We conducted 2
      experiments in which we allowed access to a target response and several
      alternatives. In Experiment 1, NCR, preceded by contingent reinforcement (CR) for
      the target, produced a reduction in the target and an increase in the
      alternatives in 2 subjects with intellectual disabilities. To separate the
      effects of NCR from the availability of alternative responses, we presented CR
      conditions to 4 subjects in Experiment 2 with and without the availability of
      alternatives. The availability of alternatives decreased the target in only 1
      subject. Subsequent manipulations showed that reductions in the target were
      solely a function of NCR for the other 3 subjects. Thus, response competition may
      have marginal effects on response suppression during NCR. 

PMID- 24114224
TI  - Some indirect effects of positive practice overcorrection.
AB  - We evaluated the effects of positive practice overcorrection (PP OC) on levels of
      motor stereotypy and appropriate engagement in the activity practiced during
      treatment with 3 young men with autism. We also measured preference for the
      practiced activities during preference probes to determine if these activities
      might acquire aversive properties as a result of the frequent pairing with PP OC.
      Treatment reduced motor stereotypy for all 3 participants, and engagement
      increased for 2 of the 3 participants. Relative preference for the activities was
      not disrupted by the implementation of PP OC, although overall contact with the
      activities decreased for 1 participant. Results from 1 participant suggest that
      PP OC may be less effective when stereotypy results in access to a more highly
      preferred activity. 

PMID- 24114225
TI  - An assessment of error-correction procedures for learners with autism.
AB  - Prior research indicates that the relative effectiveness of different error
      correction procedures may be idiosyncratic across learners, suggesting the
      potential benefit of an individualized assessment prior to teaching. In this
      study, we evaluated the reliability and utility of a rapid error-correction
      assessment to identify the least intrusive, most effective procedure for teaching
      discriminations to 5 learners with autism. The initial assessment included 4
      commonly used error-correction procedures. We compared the total number of trials
      required for the subject to reach the mastery criterion under each procedure.
      Subjects then received additional instruction with the least intrusive procedure
      associated with the fewest number of trials and 2 less effective procedures from
      the assessment. Outcomes of the additional instruction were consistent with those
      from the initial assessment for 4 of 5 subjects. These findings suggest that an
      initial assessment may be beneficial for identifying the most appropriate error
      correction procedure. 

PMID- 24114226
TI  - Effects of two variations of differential reinforcement on prompt dependency.
AB  - Prompt dependency is an often referenced but little studied problem. The current
      study evaluated 2 iterations of differential reinforcement (DR) for overcoming
      prompt dependency and facilitating skill acquisition with 4 individuals who had
      been diagnosed with an autism spectrum disorder (ASD). Preference and reinforcer
      assessments were conducted to determine moderately and highly preferred
      reinforcers for each participant. Three sets of word-picture relations were
      taught to each of the participants using 1 of 3 DR procedures. Reinforcement for
      independent responses entailed delivery of the highest preference stimulus across
      all 3 procedures. Consequences for prompted responses entailed delivery of the
      highest preference stimulus (no DR), delivery of the moderately preferred
      stimulus (DR high/moderate), or no delivery of reinforcers (DR high/extinction).
      Results indicated that the DR high/moderate condition was most effective for 3 of
      4 participants, whereas the DR high/extinction condition was most effective for
      the remaining participant. 

PMID- 24114227
TI  - Behavioral economic analysis of demand for fuel in North America.
AB  - Emerging research clearly indicates that human behavior is contributing to
      climate change, notably, the use of fossil fuels as a form of energy for everyday
      behaviors. This dependence on oil in North America has led to assertions that the
      current level of demand is the social equivalent to an "addiction." The purpose
      of this study was to apply behavioral economic demand curves-a broadly applicable
      method of evaluating relative reinforcer efficacy in behavioral models of
      addiction-to North American oil consumption to examine whether such claims of oil
      addiction are warranted. Toward this end, we examined government data from the
      United States and Canada on per capita energy consumption for transportation and
      oil prices between 1995 and 2008. Our findings indicate that consumption either
      persisted or simultaneously increased despite sharp increases in oil price per
      barrel over the past decade. 

PMID- 24114228
TI  - Effects of operant discrimination training on the vocalizations of nonverbal
      children with autism.
AB  - We evaluated the effects of operant discrimination training (ODT) on the
      vocalizations of 3 boys with autism. We compared ODT to a stimulus-stimulus
      pairing (SSP) condition and a control condition in an adapted alternating
      treatments design. ODT increased the target vocalizations of all participants
      compared to the control condition, and its effects were similar to SSP. All
      participants preferred ODT to SSP. 

PMID- 24114229
TI  - Using video modeling with substitutable loops to teach varied play to children
      with autism.
AB  - Children with autism often engage in repetitive play with little variation in the
      actions performed or items used. This study examined the use of video modeling
      with scripted substitutable loops on children's pretend play with trained and
      untrained characters. Three young children with autism were shown a video model
      of scripted toy play that included a substitutable loop that allowed various
      characters to perform the same actions and vocalizations. Three characters were
      modeled with the substitutable loop during training sessions, and 3 additional
      characters were present in the video but never modeled. Following video modeling,
      all the participants incorporated untrained characters into their play, but the
      extent to which they did so varied. 

PMID- 24114230
TI  - The effects of tact training on the emergence of categorization and listener
      behavior in children with autism.
AB  - We evaluated the effects of tact training on the emergence of categorization and
      listener behavior using a nonconcurrent multiple baseline design across 2
      children with autism. Participants learned to tact the category name of 9
      pictures that belonged to 3 different categories. We assessed whether
      participants accurately matched pictures by category and selected the correct
      comparisons when hearing their category names. After training, participants
      categorized and emitted listener behavior. One participant did not categorize
      until asked to tact the samples. These results suggest that tact training may be
      an efficient way to produce listener and categorization in children diagnosed
      with autism. 

PMID- 24114231
TI  - Increasing responding to others' joint attention directives using circumscribed
      interests.
AB  - Children with autism show significant deficits in joint attention (JA), which
      occurs when 2 people engage in verbalizations, gestures, or eye contact with each
      other and a common object. Children with autism also exhibit intense interests in
      specific topics (i.e., circumscribed interests; CI). This study investigated the
      effectiveness of teaching responding to JA directives (RJA) to 3 children with
      autism while engaged in CI activities. RJA increased during intervention and
      generalized from CI to preferred activities. 

PMID- 24114232
TI  - The effect of rules on differential reinforcement of other behavior.
AB  - Previous research on the treatment of problem behavior has shown differential
      reinforcement of other behavior (DRO) to be an effective behavior-reduction
      procedure. However, the extent to which presession descriptions of the DRO
      contingency enhance intervention effects has not been examined. In the current
      study, we compared a condition in which a presession rule that described the DRO
      contingency was given to a condition in which no rule was given for 4
      participants. The target behavior was toy play, which served as an analogue to
      problem behavior maintained by automatic reinforcement. Results showed that DRO
      was more efficient for 1 participant and more effective for 2 participants when a
      rule was given. 

PMID- 24114233
TI  - Precursor manic behavior in the assessment and treatment of episodic problem
      behavior for a woman with a dual diagnosis.
AB  - A functional analysis examined the relation between consequences that maintained
      episodic problem behavior (aggression, property destruction, and elopement) in
      the presence and absence of manic behaviors (MB). Results suggested that the
      presence of MB was correlated with the sensitivity of problem behavior to
      attention as a reinforcer during a functional analysis and that problem behaviors
      were maintained by attention. Noncontingent reinforcement was subsequently
      implemented and demonstrated to be effective in reducing problem behavior during
      the presence of manic behaviors. 

PMID- 24114234
TI  - Including unfamiliar stimuli in preference assessments for young children with
      autism.
AB  - This study examined the inclusion of familiar and unfamiliar stimuli in a paired
      stimulus preference assessment and subsequent progressive-ratio reinforcer
      assessment for 3 children with an autism spectrum disorder (ASD). Results showed
      that highly preferred unfamiliar stimuli functioned as reinforcers. These
      findings suggest that the inclusion of unfamiliar stimuli in preference
      assessments may facilitate the identification of additional reinforcers for
      children with an ASD. 

PMID- 24114235
TI  - The effects of awareness training on tics in a young boy with Tourette syndrome,
      Asperger syndrome, and attention deficit hyperactivity disorder.
AB  - Previous research has shown habit reversal training (HRT) to be effective in
      reducing tics. In some studies, tics have been reduced by implementing only a few
      components of HRT. The current study investigated the first step, awareness
      training, for treating tics in a young boy with Asperger syndrome, Tourette
      syndrome, and attention deficit hyperactivity disorder. The results showed a
      reduction in all tics. 

PMID- 24114236
TI  - Positive reinforcement as treatment for problem behavior maintained by negative
      reinforcement.
AB  - Functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) have
      been useful in determining function-based treatments for problem behavior.
      Recently, however, researchers have evaluated the use of arbitrary reinforcers
      (e.g., positive reinforcers) to decrease problem behavior maintained by negative
      reinforcement, particularly in the absence of extinction. We provide a brief
      review of recent research on this topic and discuss implications regarding
      mechanisms, practice, and future research directions. 

PMID- 24114237
TI  - Influence of calcium lactate and modified atmosphere on respiration rate, optical
      and mechanical properties of sliced persimmon.
AB  - The aim of this study was to evaluate the effect of a modified atmosphere (5% and
      10% of CO2) and calcium lactate treatment on the respiratory metabolism of
      minimally processed persimmon. A static system to measure changes in the
      composition of the headspace was used. Composition, texture and colour were also
      analysed. Persimmon slices were evaluated immediately after the washing treatment
      and after the O2 composition had decreased to 17% to avoid changes in the
      metabolic pathway. All samples were stored at 4 C. The results showed that
      modified atmosphere did not affect compositional properties, although there was a
      slight increase in pH values at the end of each treatment. Calcium lactate
      treatment reduced the respiration rate, in terms of O2, in samples kept in air.
      Additionally, a calcium lactate effect was immediately observed on mechanical
      properties after the washing stage. On the other hand, luminosity and b*
      coordinate decreased in unwashed and calcium lactate samples kept in 5% CO2. 

PMID- 24114238
TI  - Development and validation of risk models and molecular diagnostics to permit
      personalized management of cancer.
AB  - Despite the advances made in cancer management over the past few decades,
      improvements in cancer diagnosis and prognosis are still poor, highlighting the
      need for individualized strategies. Toward this goal, risk prediction models and
      molecular diagnostic tools have been developed, tailoring each step of risk
      assessment from diagnosis to treatment and clinical outcomes based on the
      individual's clinical, epidemiological, and molecular profiles. These approaches
      hold increasing promise for delivering a new paradigm to maximize the efficiency
      of cancer surveillance and efficacy of treatment. However, they require stringent
      study design, methodology development, comprehensive assessment of biomarkers and
      risk factors, and extensive validation to ensure their overall usefulness for
      clinical translation. In the current study, the authors conducted a systematic
      review using breast cancer as an example and provide general guidelines for risk
      prediction models and molecular diagnostic tools, including development,
      assessment, and validation.

PMID- 24114240
TI  - A systematic review and meta-analysis of the ethnic density effect in psychotic
      disorders.
AB  - PURPOSE: A number of studies have found an ethnic density effect in psychotic
      disorders, where the incidence for ethnic minorities increases as the
      neighbourhood proportional ethnic composition decreases [Morgan and Hutchinson,
      Psychol Med 40:705-709, (2010); Singh, Psychol Med 39:1402-1403, (2009);
      Schofield et al., Psychol Med 41:1263-1269, (2010)]. However, there is a mixed
      picture with some studies reporting no effect [Schofield et al., Psychol Med
      41:1263-1269, (2010)]. This review aimed to establish the existence of the effect
      by answering the review question: is there an ethnic density dose effect in the
      prevalence of psychotic disorders? METHODS: A systematic review and meta-analysis
      was conducted by two independent reviewers using PsychINFO, Web of Science and
      PubMed databases. Studies were measured against eligibility criteria and then
      pooled with any discrepancies discussed between reviewers. Studies were then
      assessed for quality using a standardised quality assessment. RESULTS: In total,
      eight studies were included. A meta-analysis was conducted which found that the
      incidence of psychotic disorders was higher in low ethnic density areas than high
      ethnic density areas. A narrative synthesis reflected the complexity when results
      were broken down by individual ethnic groups where some ethnic groups had inverse
      or no associations with ethnic density. The synthesis also analysed
      methodological differences between studies. CONCLUSIONS: The review reports
      evidence of an overall ethnic density dose effect for ethnic minorities, but with
      more mixed results for individual ethnic groups. The possible mechanisms behind
      this effect are explored, including exposure to racism, social capital and social
      cohesion hypotheses. The wide-ranging implications of the review are discussed
      along with recommendations for future research to continue to inform public
      health policy.

PMID- 24114239
TI  - A proteolytic pathway that controls glucose uptake in fat and muscle.
AB  - Insulin regulates glucose uptake by controlling the subcellular location of GLUT4
      glucose transporters. GLUT4 is sequestered within fat and muscle cells during low
      insulin states, and is translocated to the cell surface upon insulin stimulation.
      The TUG protein is a functional tether that sequesters GLUT4 at the Golgi matrix.
      To stimulate glucose uptake, insulin triggers TUG endoproteolytic cleavage.
      Cleavage accounts for a large proportion of the acute effect of insulin to
      mobilize GLUT4 to the cell surface. During ongoing insulin exposure, endocytosed
      GLUT4 recycles to the plasma membrane directly from endosomes, and bypasses a TUG
      regulated trafficking step. Insulin acts through the TC10alpha GTPase and its
      effector protein, PIST, to stimulate TUG cleavage. This action is coordinated
      with insulin signals through AS160/Tbc1D4 and Tbc1D1 to modulate Rab GTPases, and
      with other signals to direct overall GLUT4 targeting. Data support the idea that
      the N-terminal TUG cleavage product, TUGUL, functions as a novel ubiquitin-like
      protein modifier to facilitate GLUT4 movement to the cell surface. The C-terminal
      TUG cleavage product is extracted from the Golgi matrix, which vacates an
      "anchoring" site to permit subsequent cycles of GLUT4 retention and release.
      Together, GLUT4 vesicle translocation and TUG cleavage may coordinate glucose
      uptake with physiologic effects of other proteins present in the GLUT4-containing
      vesicles, and with potential additional effects of the TUG C-terminal product.
      Understanding this TUG pathway for GLUT4 retention and release will shed light on
      the regulation of glucose uptake and the pathogenesis of type 2 diabetes. 

PMID- 24114241
TI  - Review of new guidelines for the management of glucocorticoid induced
      osteoporosis.
AB  - The chronic use of glucocorticoids results in osteoporosis. Several sets of
      guidelines have been published on the management of glucocorticoid induced
      osteoporosis (GIO). These guidelines vary on their focus and highlight different
      aspects of the current concepts in the management of GIO. In this current
      article, we summarize recent guidelines for management of GIO and highlight
      similarities and differences as well as address some of the controversies
      generated by these guidelines. 

PMID- 24114242
TI  - Reply to Letter regarding article by Wang et al: "Internal fixation of distal
      tibiofibular syndesmotic injuries: a systematic review with meta-analysis".

PMID- 24114243
TI  - Biomechanical comparison of two angular stable plate constructions for
      periprosthetic femur fracture fixation.
AB  - PURPOSE: Fractures of the femur associated with total hip arthroplasty are a
      significant concern in orthopaedic and trauma surgery. However, little is known
      about the different biomechanical properties of internal fixation systems in
      combination with periprosthetic fractures. In this study two new internal
      fixation systems for periprosthetic fractures are investigated using a cadaver
      fracture model simulating a Vancouver B1 periprosthetic femur fracture. METHODS:
      Nine pairs of fresh-frozen cadaver femurs were scanned by dual X-ray
      absorptiometry. Cementless total hip prostheses were implanted and a
      periprosthetic femur fracture was simulated. Fractures were randomly fixed either
      with the fixed angle locking attachment plate (LAP(r), Depuy Synthes(r),
      Solothurn, Switzerland) or the variable angle non-contact bridging plate (NCB(r),
      Zimmer GmbH, Winterthur, Switzerland). Each construct was cyclically loaded to
      failure in axial compression. RESULTS: Axial stiffness and cycles to failure were
      significantly higher in the NCB group. Both systems were able to be fixed well
      around the femoral stem. CONCLUSION: The two different internal fixation systems
      for periprosthetic fractures differed significantly in our setup. The non-contact
      bridging plate system revealed significantly higher failure load and may be the
      preferred option where high stability and load capacity is needed right after
      operation.

PMID- 24114244
TI  - Variability of gait in the early postoperative period of total knee arthroplasty
      with different surgical technique.
AB  - PURPOSE: The purpose of this study was to work out an objective and sensitive
      method for the early postoperative period following total knee arthroplasty (TKA)
      in which analysis of the gait parameters is possible and also to investigate the
      influence of different surgical approaches for TKA on the gait during stepping in
      the first three months of the postoperative period. METHODS: Three groups of
      patients: age-matched healthy elderly patients as a control group, patients
      operated upon by the conventional technique and finally by the minimally invasive
      technique combined with computer-assisted navigation. All three groups included
      ten patients. The motions of knee, shoulder and pelvis were measured by ZEBRIS
      ultrasound-based system preoperatively plus six and 12 weeks postoperatively.
      From the joint motion, the variability of cadence, and the variability of knee
      joint motion and that of pelvis and shoulder girdle was determined. RESULTS:
      Osteoarthritis (OA) of the knee joint and TKA using both operation techniques
      significantly influenced the variability of stepping parameters compared to the
      controls. In the early postoperative period a significant difference was detected
      between the two groups of the operated patients in all parameters. CONCLUSION:
      Our data prove that our method seems appropriate to provide objective measurement
      of the gait in the early postoperative period. The variability of motion of the
      patient groups approaches that of the healthy control group steadily, but does
      not reach them.

PMID- 24114245
TI  - Reply to Comment on Zhou et al.: Do we really need closed-suction drainage in
      total hip arthroplasty? A meta-analysis.

PMID- 24114246
TI  - Platelet-rich-plasma injections for chronic plantar fasciitis.

PMID- 24114247
TI  - Reply to letter to the editor: Platelet-rich plasma injections for chronic
      plantar fasciitis.

PMID- 24114248
TI  - Subclinical bilateral involvement of the hip in patients with slipped capital
      femoral epiphysis: a multicentre study.
AB  - PURPOSE: This study was conducted to assess the posterior inclination of the
      contralateral femoral epiphysis in patients with unilateral slipped capital
      femoral epiphysis (SCFE). METHODS: The posterior sloping angle (PSA) was measured
      using lateral radiographs in 67 patients with a unilateral SCFE and in 41 age
      matched normal controls. A symptomatic epiphyseal slip was defined as the
      development of SCFE. RESULTS: The contralateral PSA in SCFE patients was more
      widely distributed and significantly larger compared to controls (15.0 degrees 
      vs. 9.0 degrees , p < 0.0001). Forty-seven hips (70.1%) had a PSA of greater than
      12.8 degrees , which was +2SD of the control hips. Of the 65 hips excluding the
      two cases with prophylactic pinning, 11 hips (16.9%) eventually developed a
      contralateral SCFE during adolescence and their PSA at the initial visit was
      significantly larger compared to patients without a contralateral SCFE (18.0
      degrees  vs. 14.3 degrees , p < 0.005) with a cutoff value of 19 degrees .
      CONCLUSIONS: These findings suggested the possibility of bilateral hip
      involvement in SCFE patients. Hips with greater degrees of PSA (> 19 degrees )
      are likely to become symptomatic.

PMID- 24114249
TI  - Antithrombotic prophylaxis in major orthopaedic surgery: an historical overview
      and update of current recommendations.
AB  - The risk of venous thromboembolism following major orthopaedic procedures, such
      as joint arthroplasty and hip fracture surgery, are well recognised and represent
      one of the major challenges in orthopaedic practice, having in mind the
      increasing number of arthroplasties of the hip and knee done worldwide per year
      and their successful outcome. This potentially fatal complication remains a
      challenge in orthopaedic practice. The percentage of patients in whom
      antithrombotic prophylaxis has not been administrated or has been inadequate may
      reach 50%. Until recently, anticoagulant prophylaxis with low molecular weight
      heparins (LMWHs) has been a "gold standard". LMWHs are indirect inhibitors of the
      clotting factors Xa and thrombin and are administered by daily subcutaneous
      injection. Their efficacy has been proven in numerous clinical trials and the
      rate of complications with their use is relatively low. However these compounds
      are associated with a failure rate and are inconvenient to administer, requiring
      subcutaneous injection, leading to inadequate compliance. For these reasons
      postoperative thrombembolism continues to occur in up to 10% of this patient
      population. Recently, novel oral anticoagulants have been introduced into
      practice for thromboprophylaxis after joint arthroplasy and hip fracture surgery.
      These drugs are direct thrombin inhibitors (dabigatran) or direct factor Xa
      inhibitors (rivaroxaban, apixaban and edoxaban). These oral drugs have the same
      efficacy as the LMWHs with the same or slightly more clinically significant
      haemorrhage as their main side effect. Their ease of administration and
      favourable clinical profile makes them an important addition to the therapeutic
      armamentarium available for venous thromboprophylaxis. In this paper we review
      the aetiology and pathogenesis of venous thromboembolism and present the various
      alternatives for its prevention after major orthopaedic surgical procedures with
      emphasis on the new oral drugs.

PMID- 24114250
TI  - A cementless hip system with a new surface for osseous integration.
AB  - PURPOSE: The failure of total hip systems caused by wear-particle-induced
      loosening has focused interest on factors potentially affecting wear rate.
      Remnants of the blasting material were reported on grit-blasted surfaces for
      cementless fixation. These particles are believed to cause third-body wear and
      implant loosening. The purpose of this study was to evaluate the early clinical
      and radiological outcomes of a cementless hip system with a new, contamination
      free, roughened surface with regard to prosthesis-related failures. METHODS:
      Between May 2004 and March 2009, 202 consecutive primary total hip arthroplasties
      (THAs) (192 patients with a mean age of 62.6 years) were performed using a
      cementless stem (Hipstar(r)) and a hemispherical acetabular cup (Trident(r)).
      RESULTS: At a minimum follow-up of two years, five revisions (2.5%) due to
      aseptic loosening of the stem and three (1.5%) of the cup were necessary. The
      cumulative rate of prostheses survival, counting revision of both components and
      with aseptic failure as end point, was 92.9% at 8.8 years. Radiolucent lines up
      to three millimetres were evaluated in the proximal part of the femur in 61% of
      cases. CONCLUSIONS: Although the incidence of radiolucent lines was decreased,
      the revision rate was considerably increased compared to other uncemented hip
      implants with grit-blasted surfaces in the short- to mid-term follow-up of our
      study. Subsequent studies are needed to confirm whether these changes in implant
      material and surface affect the radiological and clinical outcome in the long
      term.

PMID- 24114251
TI  - Platelet-rich plasma prevents blood loss and pain and enhances early functional
      outcome after total knee arthroplasty: a prospective randomised controlled study.
AB  - PURPOSE: The purpose of this study was to determine whether platelet-rich plasma
      (PRP) might prevent blood loss and postoperative pain and expedite wound healing
      following total knee arthroplasty (TKA). METHODS: Forty consecutive patients with
      knee arthritis who were matched for age, sex and body mass index (BMI) were
      randomly allocated to either receive or not receive PRP application over the
      wound, including capsule, medial and lateral recesses, during TKA. Postoperative
      haemoglobin, blood loss, blood transfusion, visual analogue scale (VAS) score,
      wound score, Knee Society Score (KSS) and Western Ontario and McMaster
      Osteoarthritis Index (WOMAC) score were recorded and evaluated. RESULTS: The
      platelet-rich plasma and control groups comprised 17 and 23 patients,
      respectively. The PRP group recorded significantly less reduction in haemoglobin
      and need for blood transfusion (p = 0.00 and p = 0.001, respectively),
      experienced less pain (p = 0.00) and required fewer narcotics than the control (p
      = 0.00). There was significant difference in range of motion (ROM) at three
      months (p = 0.01), no significant difference in wound scores (p = 0.311) and
      significant difference in KSS and WOMAC scores at 12 weeks (p = 0.00, 0.00).
      However no significant difference was found at six months. CONCLUSIONS: PRP has
      significant effect in preventing blood loss, postoperative pain and need for
      narcotics after TKA and has a positive effect on short-term clinical outcome.

PMID- 24114252
TI  - Factors contributing to severe early childhood caries in south-west Germany.
AB  - OBJECTIVES: The purpose of this study is to investigate the contribution of
      selected variables to the occurrence of severe early childhood caries (S-ECC) in
      3- to 5-year-old kindergarten children. METHODS: A cross-sectional study was
      conducted in 2010 in 30 randomly selected kindergartens in the German Rhein
      Neckar district. After informed consent, parents were asked to complete a
      questionnaire. The oral examinations took place in the selected kindergartens and
      the WHO methods as well as the criteria proposed by the American Academy of
      Pediatric Dentistry were followed. Logistic regression was applied to explore the
      main factors contributing to S-ECC in a multivariate model. RESULTS: In all,
      1,007 children aged 3 to 5 years with an average age of 4.1 (SD = 0.8) years were
      examined. Five variables were associated significantly with the occurrence of S
      ECC: breastfeeding for more than 12 months (OR = 3.27), use of the nursing bottle
      in bed (OR = 3.08), start of tooth brushing after the first anniversary (OR =
      2.42), regular visits at the dentists (OR = 0.14) and mother with immigration
      background (OR = 4.05). Prevalence rate of S-ECC was 9.5 %. The mean d(3+4)mft
      values were 5.69 (S-ECC group) and 0.23 (non-S-ECC group). CONCLUSION: These
      results show that occurrence of S-ECC is a complex interaction between
      socioeconomic, psychological and behavioural factors of parents. New and specific
      ways to provide preventive dental care for toddlers and infants of caries risk
      groups have to be developed. CLINICAL RELEVANCE: Parents of newborn children have
      to receive information about timely start of tooth brushing and adequate use of
      nursing bottles.

PMID- 24114253
TI  - 9, 10-Bis(8-Quinolinoxymethyl)Anthracene--A Fluorescent Sensor for Nanomolar
      Detection of Cu(2+) with Unusual Acid Stability of Cu(2+)-Complex.
AB  - In this work, the dipod 9,10-bis(8-quinolinoxymethyl)anthracene (1) and for
      comparison, monopod 9-(8-quinolinoxymethyl)anthracene (2) have been synthesized.
      The fluoroionophore 1 in pH 7.1 HEPES buffered CH3CN:H2O (4:1 v/v) solution shows
      quenching only with Cu(2+) with lowest limit of detection 150 nM, amongst various
      metal ions. Fluoroionophore 1 could also be applied to sense Co(2+) with lowest
      limit of detection 600 nM. By modulating the pH of the solution and concentration
      of Cu(2+), 1 shows respective "On-Off-On" and "On-Off" fluorescent switching. The
      self-assembly of two Cu(2+) ions and two molecules of fluoroionophore 1 to form
      closed structure [Cu2(L)2](4+) seems to be responsible for nanomolar sensitivity
      towards Cu(2+). The combination of delayed second protonation of 1 (pK(a2) = 2.6)
      and stepwise protonation of [Cu2 L2](4+) causes unusual stability of
      [Cu(LH)2](4+) even at pH < 2.

PMID- 24114254
TI  - Tuning Photophysical and Electrochemical Properties of Phosphorescent
      Heteroleptic Iridium Complex Salts-as Chemosensors.
AB  - Photophysical and electrochemical studies of cyclometalated cationic heteroleptic
      iridium(III) complex salts have been carried out. For these complex salts the
      intense absorption bands appeared around 263 nm and are assigned to spin-allowed
      pi-pi* transitions of phenanthroline ligands. Moderately intense and weak
      absorption bands observed around 341 and 440 nm, respectively. These bands are
      assigned to spin-allowed metal to ligand charge transfer (1)MLCT and (3)MLCT
      transitions, respectively. The influence of anions and proton on the
      photophysical and electrochemical studies were also carried out. The emission
      wavelength was red shifted and emission color changed from yellow to red by the
      addition of CF3CO2H. The solution color changed from green to brown and the
      emission was quenched by the addition anions such as of F(-), CH3COO(-) and
      H2PO4(-).

PMID- 24114255
TI  - Urban sediment contamination in a former Hg mining district, Idrija, Slovenia.
AB  - Road sediments from gully pots of the drainage system and stream sediments from
      local streams were investigated for the first time in the urban area of Idrija
      town, the central part of the second largest and strongly contaminated Hg mining
      district in the world. Hg concentrations in road sediments were lower than in
      stream sediments. They ranged from 16 to 110 mg/kg (Md = 29 mg/kg) for <0.125 mm
      particles and from 7 to 125 mg/kg (Md = 35 mg/kg) for <0.04 mm particles, while
      Hg concentrations in stream sediments ranged from 10 to 610 mg/kg (Md = 95 mg/kg)
      for <0.125 particles and from 10 to 440 mg/kg (Md = 105 mg/kg) for <0.04 mm
      particles. High Hg loadings in stream sediments were successfully linked with
      identified mercury sources (rocks containing mercury ore, areas of former ore
      roasting sites, ore residue dumps), because they are located in the drainage
      areas of streams, from which the sediments were collected. Links between Hg
      loadings in road sediments and identified mercury sources were not recognized.
      Solid phases of Hg were determined by thermo-desorption technique and are similar
      for both types of sediments. Results show the occurrence of three different
      forms: elemental mercury, mercury bound to matrix components and cinnabar.
      Approximately 50 % of Hg in samples consist of non-cinnabar fractions. This is
      important, since they are potentially bioavailable. An interesting new discovery
      according to previous research of environmental media from Idrija area by solid
      phase Hg thermo-desorption technique is that elemental mercury was determined in
      almost all investigated sediments in minor amounts (Md = 3 %).

PMID- 24114256
TI  - Unsuccessful treatment of severe pyruvate carboxylase deficiency with
      triheptanoin.
AB  - Pyruvate carboxylase (PC) deficiency (OMIM 266150) is an autosomal recessive
      disorder that usually presents with lactic acidaemia and severe neurological
      dysfunction, leading to death in infancy. Because the enzyme is involved in
      gluconeogenesis and anaplerosis of the Krebs cycle, therapeutic strategies have
      included avoiding fasting and attempts to correct the defect of anaplerosis.
      Triheptanoin is a triglyceride of C7 fatty acids. The oxidation of odd chain
      fatty acids leads to the production not only of acetyl-CoA but also of propionyl
      CoA, which is an anaplerotic substrate for the Krebs cycle. One infant with PC
      deficiency has previously been treated with triheptanoin as well as citrate and 2
      chloropropionate. We report two further patients with PC deficiency, who were
      treated with triheptanoin, continuously from 11 and 21 days of age. They were
      also given citrate, aspartate and dichloroacetate. Triheptanoin did not lead to
      any clinical or biochemical improvement. The plasma and CSF lactate
      concentrations remained high with episodes of severe ketoacidosis and lactic
      acidosis. Both patients had severe hearing loss, roving eye movements, seizures
      and very limited neurodevelopmental progress; they died at the ages of 7 and 8
      months. CONCLUSION: Though triheptanoin did not alter the clinical course in our
      patients, it was well tolerated. It remains possible that less severely affected
      patients might benefit from this form of therapy.

PMID- 24114257
TI  - Lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor
      Screening Program.
AB  - In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the
      Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency
      (EPA) to implement a screening program to investigate the potential of pesticide
      chemicals and drinking water contaminants to adversely affect endocrine pathways.
      Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP)
      to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening
      assays and to produce standardized and harmonized test guidelines for regulatory
      application. In 2009, the EPA issued the first set of test orders for EDSP
      screening and a total of 50 pesticide actives and 2 inert ingredients have been
      evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro
      assays and six in vivo assays). To provide a framework for retrospective analysis
      of the data generated and to collect the insight of multiple stakeholders
      involved in the testing, more than 240 scientists from government, industry,
      academia, and non-profit organizations recently participated in a workshop titled
      "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor
      Screening Program." The workshop focused on the science and experience to date
      and was organized into three focal sessions: (a) Performance of the EDSP Tier 1
      Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical
      Applications of Tier 1 Data; and (c) Indications and Opportunities for Future
      Endocrine Testing. A number of key learnings and recommendations related to
      future EDSP evaluations emanated from the collective sessions.

PMID- 24114260
TI  - Qualitative gas chromatography-mass spectrometry analyses using amines as
      chemical ionization reagent gases.
AB  - Ammonia is a very useful chemical ionization (CI) reagent gas for the qualitative
      analyses of compounds by positive ion gas chromatography-mass spectrometry
      (GCMS). The gas is readily available, inexpensive, and leaves no carbon
      contamination in the MS source. Compounds of interest to our laboratory typically
      yield abundant protonated or ammoniated species, which are indicative of a
      compound's molecular weight. Nevertheless, some labile compounds fragment
      extensively by substitution and elimination reactions and yield no molecular
      weight information. In these cases, a CI reagent gas mixture of methylamine in
      methane prepared dynamically was found to be very useful in obtaining molecular
      weight data. Likewise, deuterated ammonia and deuterated methylamine are useful
      CI reagent gases for determining the exchangeable protons in organic compounds.
      Deuterated methylamine CI reagent gas is conveniently prepared by dynamically
      mixing small amounts of methylamine with excess deuterated ammonia. 

PMID- 24114261
TI  - False-positive rate determination of protein target discovery using a covalent
      modification- and mass spectrometry-based proteomics platform.
AB  - Detection and quantitation of protein-ligand binding interactions is important in
      many areas of biological research. Stability of proteins from rates of oxidation
      (SPROX) is an energetics-based technique for identifying the proteins targets of
      ligands in complex biological mixtures. Knowing the false-positive rate of
      protein target discovery in proteome-wide SPROX experiments is important for the
      correct interpretation of results. Reported here are the results of a control
      SPROX experiment in which chemical denaturation data is obtained on the proteins
      in two samples that originated from the same yeast lysate, as would be done in a
      typical SPROX experiment except that one sample would be spiked with the test
      ligand. False-positive rates of 1.2-2.2% and <0.8% are calculated for SPROX
      experiments using Q-TOF and Orbitrap mass spectrometer systems, respectively. Our
      results indicate that the false-positive rate is largely determined by random
      errors associated with the mass spectral analysis of the isobaric mass tag (e.g.,
      iTRAQ(r)) reporter ions used for peptide quantitation. Our results also suggest
      that technical replicates can be used to effectively eliminate such false
      positives that result from this random error, as is demonstrated in a SPROX
      experiment to identify yeast protein targets of the drug, manassantin A. The
      impact of ion purity in the tandem mass spectral analyses and of background
      oxidation on the false-positive rate of protein target discovery using SPROX is
      also discussed.

PMID- 24114262
TI  - Manual small incision cataract surgery (MSICS) with posterior chamber intraocular
      lens versus phacoemulsification with posterior chamber intraocular lens for age
      related cataract.
AB  - BACKGROUND: Age-related cataract is a major cause of blindness and visual
      morbidity worldwide. It is therefore important to establish the optimal technique
      of lens removal in cataract surgery. OBJECTIVES: To compare manual small incision
      cataract surgery (MSICS) and phacoemulsification techniques. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2013, Issue 6), Ovid MEDLINE, Ovid MEDLINE In
      Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE
      (January 1946 to July 2013), EMBASE (January 1980 to July 2013), Latin American
      and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2013),
      Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January
      1970 to July 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled
      trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 23 July 2013. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) for age-related cataract that compared MSICS and phacoemulsification. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed all studies. We
      defined two primary outcomes: 'good functional vision' (presenting visual acuity
      of 6/12 or better) and 'poor visual outcome' (best corrected visual acuity of
      less than 6/60). We collected data on these outcomes at three and 12 months after
      surgery. Complications such as posterior capsule rupture rates and other intra-
      and postoperative complications were also assessed. In addition, we examined cost
      effectiveness of the two techniques. Where appropriate, we pooled data using a
      random-effects model. MAIN RESULTS: We included eight trials in this review with
      a total of 1708 participants. Trials were conducted in India, Nepal and South
      Africa. Follow-up ranged from one day to six months, but most trials reported at
      six to eight weeks after surgery. Overall the trials were judged to be at risk of
      bias due to unclear reporting of masking and follow-up. No studies reported
      presenting visual acuity so data were collected on both best-corrected (BCVA) and
      uncorrected (UCVA) visual acuity. Most studies reported visual acuity of 6/18 or
      better (rather than 6/12 or better) so this was used as an indicator of good
      functional vision. Seven studies (1223 participants) reported BCVA of 6/18 or
      better at six to eight weeks (pooled risk ratio (RR) 0.99 95% confidence interval
      (CI) 0.98 to 1.01) indicating no difference between the MSICS and
      phacoemulsification groups. Three studies (767 participants) reported UCVA of
      6/18 or better at six to eight weeks, with a pooled RR indicating a more
      favourable outcome with phacoemulsification (0.90, 95% CI 0.84 to 0.96). One
      trial (96 participants) reported UCVA at six months with a RR of 1.07 (95% CI
      0.91 to 1.26).Regarding BCVA of less than 6/60: there were only 11/1223 events
      reported. The pooled Peto odds ratio was 2.48 indicating a more favourable
      outcome using phacoemulsification but with wide confidence intervals (0.74 to
      8.28) which means that we are uncertain as to the true effect.The number of
      complications reported were also low for both techniques. Again this means the
      review is underpowered to detect a difference between the two techniques with
      respect to these complications. One study reported on cost which was more than
      four times higher using phacoemulsification than MSICS. AUTHORS' CONCLUSIONS: On
      the basis of this review, removing cataract by phacoemulsification may result in
      better UCVA in the short term (up to three months after surgery) compared to
      MSICS, but similar BCVA. There is a lack of data on long-term visual outcome. The
      review is currently underpowered to detect differences for rarer outcomes,
      including poor visual outcome. In view of the lower cost of MSICS, this may be a
      favourable technique in the patient populations examined in these studies, where
      high volume surgery is a priority. Further studies are required with longer-term
      follow-up to better assess visual outcomes and complications which may develop
      over time such as posterior capsule opacification.

PMID- 24114263
TI  - At the crossroads of anthropology and epidemiology: current research in cultural
      psychiatry in the UK.
AB  - Cultural psychiatry research in the UK comprises a broad range of diverse
      methodologies, academic disciplines, and subject areas. Methodologies range from
      epidemiological to anthropological/ethnographic to health services research;
      mixed methods research is becoming increasingly popular, as are public health and
      health promotional topics. After briefly outlining the history of cultural
      psychiatry in the UK we will discuss contemporary research. Prominent themes
      include: the epidemiology of schizophrenia among Africans/Afro-Caribbeans,
      migration and mental health, racism and mental health, cultural identity,
      pathways to care, explanatory models of mental illness, cultural competence, and
      the subjective experiences of healthcare provision among specific ethnic groups
      such as Bangladeshis and Pakistanis. Another strand of research that is
      attracting increasing academic attention focuses upon the relationship between
      religion, spirituality, and mental health, in particular, the phenomenology of
      religious experience and its mental health ramifications, as well as recent work
      examining the complex links between theology and psychiatry. The paper ends by
      appraising the contributions of British cultural psychiatrists to the discipline
      of cultural psychiatry and suggesting promising areas for future research. 

PMID- 24114264
TI  - Can the "stripping of the boss" be more than a joke?
AB  - In January 2011, uprisings and demonstrations broke out in Egypt, and the
      reverberations of the revolution are felt up to this day. The events that lead
      President Hosni Mubarak to resign were violent, disturbing, and definitely
      serious, but at the same time they were fuelled by and caused a plethora of jokes
      and funny slogans which circulated among the protesters. Previous studies on the
      functions of humour have suggested that among other things, humour can be used to
      enhance group cohesion by lifting up the spirits or to attack the (political)
      enemy by sharp sarcasm, the duality of which is captured in the metaphors of a
      shield and a sword. The present article builds upon "Stripping the Boss: The
      Powerful Role of Humor in the Egyptian Revolution 2011" by Helmy and Frerichs
      (2013), offering another perspective on the functionality Egyptian political
      jokes grounded in the current sociological approaches to humour. It aims to argue
      that humour as an ambiguous phenomenon is unreliable in reaching serious aims and
      thus cannot be conceptualised as a predictably functioning tool in conflicts,
      although it can sometimes give insights into the functioning of a society as a
      mirror of the social reality. 

PMID- 24114266
TI  - Morris F. Collen at 100: a tribute to "the father of medical informatics".

PMID- 24114265
TI  - Factors associated with disclosure of HIV status among a cohort of individuals on
      antiretroviral therapy in British Columbia, Canada.
AB  - We sought to examine the prevalence and correlates of HIV-disclosure among
      treatment-experienced individuals in British Columbia, Canada. Study participants
      completed an interviewer-administered survey between July 2007 and January 2010.
      The primary outcome of interest was disclosing one's HIV-positive status to all
      new sexual partners within the last 6 months. An exploratory logistic regression
      model was developed to identify variables independently associated with
      disclosure. Of the 657 participants included in this analysis, 73.4 % disclosed
      their HIV-positive status to all of their sexual partners. Factors independently
      associated with non-disclosure included identifying as a woman (adjusted odds
      ratio [AOR] 1.92; 95 % confidence interval [95 % CI] 1.13-3.27) or as a gay or
      bisexual man (AOR 2.45; 95 % CI 1.47-4.10). Behaviours that were independently
      associated with non-disclosure were having sex with a stranger (AOR 2.74; 95 % CI
      1.46-5.17), not being on treatment at the time of interview (AOR 2.67; 95 % CI
      1.40-5.11), and not always using a condom (AOR 1.78; 95 % CI 1.09-2.90). Future
      preventative strategies should focus on environmental and social factors that may
      inhibit vulnerable HIV-positive populations, such as women and gay or bisexual
      men, from safely disclosing their positive status. 

PMID- 24114268
TI  - Concepts relating magnetic interactions, intertwined electronic orders, and
      strongly correlated superconductivity.
AB  - Unconventional superconductivity (SC) is said to occur when Cooper pair formation
      is dominated by repulsive electron-electron interactions, so that the symmetry of
      the pair wave function is other than an isotropic s-wave. The strong, on-site,
      repulsive electron-electron interactions that are the proximate cause of such SC
      are more typically drivers of commensurate magnetism. Indeed, it is the
      suppression of commensurate antiferromagnetism (AF) that usually allows this type
      of unconventional superconductivity to emerge. Importantly, however, intervening
      between these AF and SC phases, intertwined electronic ordered phases (IP) of an
      unexpected nature are frequently discovered. For this reason, it has been
      extremely difficult to distinguish the microscopic essence of the correlated
      superconductivity from the often spectacular phenomenology of the IPs. Here we
      introduce a model conceptual framework within which to understand the
      relationship between AF electron-electron interactions, IPs, and correlated SC.
      We demonstrate its effectiveness in simultaneously explaining the consequences of
      AF interactions for the copper-based, iron-based, and heavy-fermion
      superconductors, as well as for their quite distinct IPs. 

PMID- 24114271
TI  - Mapping strain rate dependence of dislocation-defect interactions by atomistic
      simulations.
AB  - Probing the mechanisms of defect-defect interactions at strain rates lower than
      10(6) s(-1) is an unresolved challenge to date to molecular dynamics (MD)
      techniques. Here we propose an original atomistic approach based on transition
      state theory and the concept of a strain-dependent effective activation barrier
      that is capable of simulating the kinetics of dislocation-defect interactions at
      virtually any strain rate, exemplified within 10(-7) to 10(7) s(-1). We apply
      this approach to the problem of an edge dislocation colliding with a cluster of
      self-interstitial atoms (SIAs) under shear deformation. Using an activation
      relaxation algorithm [Kushima A, et al. (2009) J Chem Phys 130:224504], we
      uncover a unique strain-rate-dependent trigger mechanism that allows the SIA
      cluster to be absorbed during the process, leading to dislocation climb. Guided
      by this finding, we determine the activation barrier of the trigger mechanism as
      a function of shear strain, and use that in a coarse-graining rate equation
      formulation for constructing a mechanism map in the phase space of strain rate
      and temperature. Our predictions of a crossover from a defect recovery at the low
      strain-rate regime to defect absorption behavior in the high strain-rate regime
      are validated against our own independent, direct MD simulations at 10(5) to
      10(7) s(-1). Implications of the present approach for probing molecular-level
      mechanisms in strain-rate regimes previously considered inaccessible to atomistic
      simulations are discussed. 

PMID- 24114270
TI  - MicroRNA-26a targets ten eleven translocation enzymes and is regulated during
      pancreatic cell differentiation.
AB  - Ten eleven translocation (TET) enzymes (TET1/TET2/TET3) and thymine DNA
      glycosylase (TDG) play crucial roles in early embryonic and germ cell development
      by mediating DNA demethylation. However, the molecular mechanisms that regulate
      TETs/TDG expression and their role in cellular differentiation, including that of
      the pancreas, are not known. Here, we report that (i) TET1/2/3 and TDG can be
      direct targets of the microRNA miR-26a, (ii) murine TETs, especially TET2 and
      TDG, are down-regulated in islets during postnatal differentiation, whereas miR
      26a is up-regulated, (iii) changes in 5-hydroxymethylcytosine accompany changes
      in TET mRNA levels, (iv) these changes in mRNA and 5-hydroxymethylcytosine are
      also seen in an in vitro differentiation system initiated with FACS-sorted adult
      ductal progenitor-like cells, and (v) overexpression of miR-26a in mice increases
      postnatal islet cell number in vivo and endocrine/acinar colonies in vitro. These
      results establish a previously unknown link between miRNAs and TET expression
      levels, and suggest a potential role for miR-26a and TET family proteins in
      pancreatic cell differentiation. 

PMID- 24114273
TI  - Genotoxicity evaluation of 1,2 dichlorobenzene in the Indian major carp, Catla
      catla L. using alkaline comet assay.
AB  - The genotoxic effect of 1,2 dichlorobenzene (1,2 DCB), a volatile organic
      compound in the Indian Major Carp, Catla catla L. was assessed using the alkaline
      comet assay in the gills and blood. Fish were exposed to various sub-lethal
      concentrations of 1,2 DCB in vivo. At 24 h, DNA damage scores (expressed as
      arbitrary units) increased at 0.35 and 0.7 mg/L whereas at 28 days, there was a
      statistically significant increase in the DNA damage score at all the doses
      tested (0.175, 0.23, 0.35 and 0.7 mg/L). When the DNA damage scores were
      considered in the blood samples, the trend was similar to that observed in the
      gills - significant increase at 0.35 and 0.7 mg/L at 24 h and at all doses at 28
      days. The results indicate that 1,2 DCB induces genotoxicity in the form of
      strand breaks in the DNA of fish as evidenced by the alkaline comet assay. 

PMID- 24114272
TI  - Evolutionary etiology of high-grade astrocytomas.
AB  - Glioblastoma (GBM), the most common brain malignancy, remains fatal with no
      effective treatment. Analyses of common aberrations in GBM suggest major
      regulatory pathways associated with disease etiology. However, 90% of GBMs are
      diagnosed at an advanced stage (primary GBMs), providing no access to early
      disease stages for assessing disease progression events. As such, both
      understanding of disease mechanisms and the development of biomarkers and
      therapeutics for effective disease management are limited. Here, we describe an
      adult-inducible astrocyte-specific system in genetically engineered mice that
      queries causation in disease evolution of regulatory networks perturbed in human
      GBM. Events yielding disease, both engineered and spontaneous, indicate ordered
      grade-specific perturbations that yield high-grade astrocytomas (anaplastic
      astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression
      yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS) network drives progression to grade III
      disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields
      GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to
      KRAS activation, but before grade III progression. The stochastic appearance of
      mutations identical to those observed in humans, particularly the same spectrum
      of p53 amino acid changes, supports the validity of engineered lesions and the
      ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1)
      mutation, asymptomatic low grade disease, and rapid emergence of GBM combined
      with a mesenchymal transcriptome signature reflect characteristics of primary GBM
      and provide insight into causal relationships. 

PMID- 24114274
TI  - Comparative study of organohalogen contamination between two populations of
      Eastern Atlantic loggerhead sea turtles (Caretta caretta).
AB  - We evaluated the presence of 37 organohalogen contaminants in plasma samples from
      162 juvenile and 197 adult loggerhead turtles (Caretta caretta) from the
      archipelagos of the Canary Islands and Cape Verde, respectively, and compared the
      contamination profiles found. We detected five organochlorine pesticides (OCP)
      and 16 polychlorinated biphenyls (PCBs). The concentrations of the two groups of
      contaminants were higher in turtles from the Canary Islands (OCPs, 1.04 vs. 0.37
      ng/mL; PCBs, 1.92 vs. 0.08 ng/mL). We also observed a different profile of PCB
      contamination between the two populations. In addition, there was a negative
      correlation between body size and the total concentration of PCBs in the Canary
      Islands turtles, but not in turtles from Cape Verde. The present study presents
      the first data on the organochlorine contaminants (OCs) of live turtles from
      Canary Islands. In addition, we perform a comparison of the levels and profiles
      of OCs between these two different groups of loggerhead sea turtles from the
      Eastern Atlantic. 

PMID- 24114275
TI  - Consensus statement from the International Consensus Meeting on Periprosthetic
      Joint Infection.

PMID- 24114276
TI  - Uptake of heavy metals by some edible vegetables irrigated using wastewater: a
      preliminary study in Accra, Ghana.
AB  - The heavy metals (Fe, Zn, Pb, Ni, Cr, Co, and Cd) burden in wastewater, soil, and
      vegetable samples from a wastewater irrigated farm located at KorleBu, Accra has
      been investigated. Flame atomic absorption spectrometry after microwave digestion
      using a combination of HNO3, HCl, and H2O2 (for water), and HNO3 and HCl (for
      soil and vegetables). The mean concentrations (in milligrams per kilogram) of
      heavy metals in the soil samples were in the order of Fe (171 +/- 5.22) > Zn
      (36.06 +/- 4.54) > Pb (33.35 +/- 35.62) > Ni (6.31 +/- 8.15) > Cr (3.40 +/- 3.63)
      > Co (1.36 +/- 0.31) > Cd (0.43 +/- 0.24), while the vegetables were in the order
      of Fe (183.11 +/- 161.2) > Zn (5.38 +/- 3.50) > Ni (3.52 +/- 1.27) > Pb (2.49 +/-
      1.81) > Cr (1.46 +/- 0.51) > Co (0.66 +/- 0.25) > Cd (0.36 +/- 0.15). The
      bioconcentration factors suggest environmental monitoring for the heavy metals as
      follows: Cd (0.828), Cr (0.431), Ni (0.558), Co (0.485), and Fe (1.067).
      Estimated daily intakes were very low for both children and adults except Fe
      (0.767 mg/kg/day) in children. The population that consume vegetables from the
      study area were, however, estimated to be safe based on the results obtained from
      the health risk index, which were all < <1. The sodium absorption ratio according
      to FAO (1985) classifications indicate that the wastewater in the study area is
      unsuitable for irrigation purposes. 

PMID- 24114277
TI  - Human factors and tidal influences on water quality of an urban river in Can Tho,
      a major city of the Mekong Delta, Vietnam.
AB  - In this study, we focused on water quality in an urban canal and the Mekong River
      in the city of Can Tho, a central municipality of the Mekong Delta region,
      southern Vietnam. Water temperature, pH, electrical conductivity, BOD5, CODCr,
      Na(+), Cl(-), NH4 (+)-N, SO4 (2-)-S, NO3 (-)-N, and NO2 (-)-N for both canal and
      river, and tide level of the urban canal, were monitored once per month from May
      2010 to April 2012. The urban canal is subject to severe anthropogenic
      contamination, owing to poor sewage treatment. In general, water quality in the
      canal exhibited strong tidal variation, poorer at lower tides and better at
      higher tides. Some anomalies were observed, with degraded water quality under
      some high-tide conditions. These were associated with flow from the upstream
      residential area. Therefore, it was concluded that water quality in the urban
      canal changed with a balance between dilution effects and extent of contaminant
      supply, both driven by tidal fluctuations in the Mekong River. 

PMID- 24114278
TI  - Relations between macroinvertebrates, nutrients, and water quality criteria in
      wadeable streams of Maryland, USA.
AB  - In an ongoing effort to propose biologically protective nutrient criteria, we
      examined how total nitrogen (TN) and its forms were associated with
      macroinvertebrate communities in wadeable streams of Maryland. Taxonomic and
      functional metrics of an index of biological integrity (IBI) were significantly
      associated with multiple nutrient measures; however, the highest correlations
      with nutrients were for ammonia-N and nitrite-N and among macroinvertebrate
      measures were for Beck's Biotic Index and its metrics. Since IBI metrics showed
      comparatively less association, we evaluated how macroinvertebrate taxa related
      to proposed nutrient criteria previously derived for those same streams instead
      of developing nutrient-biology thresholds. We identified one tolerant and three
      intolerant taxa whose occurrence appeared related to a TN benchmark.
      Individually, these taxa poorly indicated whether streams exceeded the benchmark,
      but combining taxa notably improved classification rates. We then extracted major
      physiochemical gradients using principal components analysis to develop models
      that assessed their influence on nutrient indicator taxa. The response of
      intolerant taxa was predominantly influenced by a nutrient-forest cover gradient.
      In contrast, habitat quality had a greater effect on tolerant taxa. When taxa
      were aggregated into a nutrient sensitive index, the response was primarily
      influenced by the nutrient-forest gradient. Multiple lines of evidence highlight
      the effects of excessive nutrients in streams on macroinvertebrate communities
      and taxa in Maryland, whose loss may not be reflected in metrics that form the
      basis of biological criteria. Refinement of indicator taxa and a nutrient
      sensitive index is warranted before thresholds in aquatic life to water quality
      are quantified. 

PMID- 24114279
TI  - Revisiting the Chesapeake Bay phytoplankton index of biotic integrity.
AB  - In 2006, a phytoplankton index of biotic integrity (PIBI) was published for
      Chesapeake Bay Lacouture et al. (Estuaries 29(4):598-616, 2006). The PIBI was
      developed from data collected during the first 18 years (1985-2002) of the
      Chesapeake Bay Program long-term phytoplankton and water quality monitoring
      programs. Combinations of up to nine phytoplankton metrics were selected to
      characterize bay habitat health according to plankton community condition in
      spring and summer seasons across four salinity zones. The independent data
      available at the time for index validation was not sufficient to test the PIBI
      because they lacked critical index parameters (pheophytin and dissolved organic
      carbon) and reference samples for some seasons and salinity zones. An additional
      8 years of monitoring data (2003-2010) are now available to validate the original
      index, reassess index performance and re-examine long-term trends in PIBI
      conditions in the Bay. The PIBI remains sensitive to changes in nutrient and
      light conditions. Evaluation of the PIBI results over the entire 1985-2010 time
      period shows no discernible trends in the overall health of Bay habitat based on
      phytoplankton community conditions. This lack of overall PIBI trend appears to be
      a combined response to declines in water clarity and improvements in dissolved
      inorganic nitrogen and dissolved phosphorus conditions in the bay. 

PMID- 24114280
TI  - Accumulation of endocrine disrupting chemicals (EDCs) in the polychaete
      Paraprionospio sp. from the Yodo River mouth, Osaka Bay, Japan.
AB  - This study presents the levels of endocrine disrupting chemicals (EDCs)
      accumulated by Paraprionospio sp. from the Yodo River mouth, Osaka Bay. Since
      high concentrations of nonylphenol (NP), bisphenol A (BP), octylphenol (OP),
      17beta-estradiol (E2), and estrone (E1) have been measured in sediment from Osaka
      Bay, some bioaccumulation could be expected particularly in benthic animals. EDCs
      were analysed in Paraprionospio sp., a dominant benthic species in Osaka Bay. The
      results showed that Paraprionospio sp. had accumulated varying concentrations
      (wet weight; w.w.) of NP at 1,460-4,410 ng/g; BP at 22.5-39.6 ng/g; OP at 18.9
      45.4 ng/g; E2 at 0.89-4.35 ng/g; and E1 at 0.06-2.50 ng/g. Accumulation of NP and
      OP were highest among the samples gathered in summer (July 2008), while
      concentrations of BP, E2, and E1 did not much differs within 3 years. EDC levels
      in Paraprionospio sp. were apparently greater than those in sediments showing
      bioaccumulation. 

PMID- 24114281
TI  - Taxonomic assessment and enzymes production by yeasts isolated from marine and
      terrestrial Antarctic samples.
AB  - The aim of the present study was to investigate the taxonomic identity of yeasts
      isolated from the Antarctic continent and to evaluate their ability to produce
      enzymes (lipase, protease and xylanase) at low and moderate temperatures. A total
      of 97 yeast strains were recovered from marine and terrestrial samples collected
      in the Antarctica. The highest amount of yeast strains was obtained from marine
      sediments, followed by lichens, ornithogenic soils, sea stars, Salpa sp., algae,
      sea urchin, sea squirt, stone with lichens, Nacella concinna, sea sponge, sea
      isopod and sea snail. Data from polyphasic taxonomy revealed the presence of 21
      yeast species, distributed in the phylum Ascomycota (n = 8) and Basidiomycota (n
      = 13). Representatives of encapsulated yeasts, belonging to genera Rhodotorula
      and Cryptococcus were recovered from 7 different Antarctic samples. Moreover,
      Candida glaebosa, Cryptococcus victoriae, Meyerozyma (Pichia) guilliermondii,
      Rhodotorula mucilaginosa and R. laryngis were the most abundant yeast species
      recovered. This is the first report of the occurrence of some species of yeasts
      recovered from Antarctic marine invertebrates. Additionally, results from enzymes
      production at low/moderate temperatures revealed that the Antarctic environment
      contains metabolically diverse cultivable yeasts, which could be considered as a
      target for biotechnological applications. Among the evaluated yeasts in the
      present study 46.39, 37.11 and 14.43 % were able to produce lipase (at 15 
      degrees C), xylanase (at 15  degrees C) and protease (at 25  degrees C),
      respectively. The majority of lipolytic, proteolytic and xylanolytic strains were
      distributed in the phylum Basidiomycota and were mainly recovered from sea stars,
      lichens, sea urchin and marine sediments. 

PMID- 24114282
TI  - Disclosure pattern and follow-up after the molecular diagnosis of BRCA/CHEK2
      mutations.
AB  - Five to 10% of all breast cancer cases are due to mutations of high penetrance
      susceptibility genes, especially BRCA1 and BRCA2. In families with known BRCA
      mutations, disclosure of genetic test results could induce relatives to undergo
      genetic testing themselves and adopt cancer risk management strategies, if
      necessary. This study examines disclosure patterns of individuals tested for
      mutations in the BRCA1, BRCA2 and CHEK2 genes to first-degree relatives with
      emphasis on a possible gender difference. It also assesses which management
      strategy is preferred by mutation-positive women in Belgium and the influence of
      psychological characteristics on communication and choice of management strategy.
      Ninety-nine adults from BRCA/CHEK2 families, selected from the Centre of Medical
      Genetics of Antwerp, were included in the study. They were provided with medical
      and psychological questionnaires, the latter being the Self-Assessment
      Questionnaire, which is the Dutch version of the Spielberger State-Trait Anxiety
      Inventory and the Dutch version of the Coping Inventory for Stressful Situations
      (CISS-NL). The survey focused on disclosure, coping and management strategies
      with special attention on possible gender differences. The influence of socio
      demographic and medical data on disclosure and cancer risk management as well as
      the influence of psychological features were examined by means of various
      statistical analyses. Ninety-nine patients were included, of whom 25 (25 %) were
      male. Eighty-seven percent of the participants informed all of their adult first
      degree relatives about their mutation status without any gender discrimination.
      Seventy-eight percent of highly-educated participants informed all of their adult
      first-degree relatives, compared to 98 % of less formally-educated participants
      (p = 0.006). The majority of mutation-positive women preferred prophylactic
      surgery to surveillance. Psychological differences appeared to have little
      influence on disclosure patterns and management strategies. The gender difference
      seems to be less pronounced than previously assumed. A striking observation,
      however, is the fact that significantly more participants who were less formally
      educated informed all of their adult first-degree relatives, compared to
      participants who were highly-educated. In our study population, most female
      mutation carriers opted for prophylactic surgery. Since the study population is
      small, further studies are needed to enhance the generalizability of these
      results.

PMID- 24114283
TI  - Introduction to the special issue on genetic counseling: a global perspective.
AB  - This special issue of the Journal of Genetic Counseling is focused on the global
      genetic counselling community and includes commentaries, original research and
      multiple brief reports describing both established formal genetic counselling
      services and training programs as well as services and programs that are
      currently in development. 

PMID- 24114284
TI  - Benefits and harm of niacin and its analog for renal dialysis patients: a
      systematic review and meta-analysis.
AB  - PURPOSE: Clinical trials have shown that niacin and its analog, niacinamide,
      significantly reduce serum phosphate in patients undergoing dialysis. This review
      aimed to assess the benefits and harm of niacin and niacinamide in renal dialysis
      patients. METHODS: PubMed, EMBASE, and Cochrane Library were searched, without
      language limitation, randomized controlled trials (RCTs). Standard methods,
      consistent with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines, were used. Reviewer Manager software, version 5.2,
      was used for meta-analysis. RESULTS: Five RCTs with a sample size of 230 patients
      were included. The meta-analysis showed that niacin and niacinamide significantly
      decreased serum phosphorus levels [weight mean difference (WMD) -0.88; 95 %
      confidence interval (CI) -1.19 to -0.57] as well as the calcium * phosphorus
      product (Ca * P) (WMD -9.15; 95 % CI -13.23 to -5.08), and increased high-density
      lipoprotein (HDL) levels (WMD 9.30; 95 % CI 5.86-12.74) in renal dialysis
      patients. Niacin significantly increased the risk of flushing [relative risk (RR)
      33; 95 % CI 4.71-232.12] in these patients, while the risk of thrombocytopenia
      was significantly increased in the niacinamide group (RR 2.82; 95 % CI 1.14
      6.94). However, sensitivity analysis showed that our finding regarding
      thrombocytopenia should be regarded with a low degree of certainty. CONCLUSION:
      Niacin and its analog effectively improved phosphorus metabolism in renal
      dialysis patients. However, niacin can cause flushing and niacinamide probably
      cause thrombocytopenia. Further larger sample size and well-designed RCTs are
      needed.

PMID- 24114285
TI  - Prevalence and related factors of the absence of anemia among Chinese chronic
      hemodialysis patients: a multicenter cross-sectional study.
AB  - BACKGROUND: Some chronic hemodialysis (HD) patients can maintain normal
      hemoglobin levels without requiring erythropoiesis-stimulating agents (ESAs).
      However, the prevalence and the factors associated with this condition in Chinese
      chronic HD patients have not been reported. The aim of this study was to
      investigate clinical features, iron metabolism, and other characteristics to
      survey the prevalence rate and the related factors of this condition among
      Chinese chronic HD patients. METHODS: A total of 1,318 chronic HD patients
      participated in this study. The patients were classified into a non-ESA group (n
      = 11) and an ESA group (n = 1,307). The r-HuEPO-independent (non-ESA) HD patients
      were defined as having hemoglobin greater than 12 g/dl for more than 6 months
      without r-HuEPO injection, blood transfusion, or androgen therapy.
      Epidemiological and laboratory data were collected. Renal sonography was also
      performed on each patient to evaluate the formation of renal and liver cysts, and
      the number and size of the cysts were recorded. RESULTS: Approximately 0.84 % of
      all HD patients were found to be r-HuEPO independent. The non-ESA group had a
      higher proportion of men (79.6 vs. 58.3 %), a longer duration of renal
      replacement therapy (RRT) (8.6 +/- 6.1 vs. 5.1 +/- 3.3 years), a higher
      prevalence of adult polycystic kidney disease (APKD) (46.3 vs. 9.7 %), a higher
      prevalence of hepatitis C virus (HCV) liver disease (26.2 vs. 3.2 %, P < 0.01),
      and had older patients (63.3 +/- 13.6 vs. 49.6 +/- 13.5 years). Endogenous
      erythropoietin levels in the non-ESA group were significantly higher than those
      in the ESA group (61.8 +/- 27.1 vs. 29.3 +/- 11.7 mU/ml). Non-ESA patients had a
      significantly higher number of renal (38.1 vs. 13.2 %) and hepatic cysts (9.3 vs.
      1.9 %), which were also larger in size (2.9 +/- 1.6 vs. 1.3 +/- 0.3 cm) compared
      with those of patients in the ESA group. No significant difference in iron
      metabolism was found between two groups. In the multivariate Cox analysis, the
      independent predictor factors for the absence of anemia in these HD patients were
      the number of renal cysts >6 cysts (95 % CI 1.058-1.405; P = 0.00), endogenous
      erythropoietin levels (95 % CI 1.139-1.361; P = 0.05), HCV+ liver disease (95 %
      CI 1.129-1.316; P = 0.01), and time on RRT (95 % CI 1.019-1.263; P = 0.05).
      CONCLUSIONS: To our knowledge, this study is the first to report on r-HuEPO
      independence among Chinese HD patients. The prevalence among Chinese chronic HD
      patients is significantly lower than that reported in the literature. Factors
      contributing to this condition are complex and multiple. The frequency of this
      condition is higher in men and in older patients with long-term RRT, in patients
      with HCV+ liver disease, and in APKD patients. This condition is associated with
      increased endogenous erythropoietin production and the presence of renal and
      hepatic cysts.

PMID- 24114286
TI  - A survey of patterns of practice on palliative radiation therapy for bone
      metastasis in Korea.
AB  - PURPOSE: The aim of this study was to understand the practice patterns of
      palliative radiation therapy for bone metastasis in Korea among Korean radiation
      oncologists by survey and to determine the decision factors affecting the
      prescription of radiation therapy fractionation schedules. METHODS: An Internet
      based survey was performed from October 5 to October 23, 2009, among 177 active
      full members of the Korean Society for Radiation and Oncology (KOSRO). The survey
      questionnaire included general information about the respondent, three types of
      clinical scenario, depending on the life expectancy of the patients, and the
      decision factors that affected the prescription of a radiation therapy schedule.
      RESULTS: The most prescribed schedule was 30 Gy in 10 fractions regardless of the
      life expectancy of the patient. Also, it was found that a single fraction was
      seldom prescribed routinely in Korea. An increasing number prescribed fewer than
      10 fractions as the life expectancy shortened; however, the prescription rate of
      a single fraction was still low. The general performance (and/or accompanying
      diseases) of patients and the life expectancy were the most considered factors in
      deciding the prescription of radiation therapy. CONCLUSIONS: Despite the abundant
      evidence supporting the equivalence of single- and multi-fraction radiation
      therapy, still, most Korean radiation oncologists continue to prescribe multi
      fraction schedules depending on the general performance and life expectancy of
      the patients. Thus, we confirmed that there was a gap between evidence and
      practice, and treatment prescriptions can be strongly affected by decision
      factors other than published literature results.

PMID- 24114287
TI  - Fms-like tyrosine kinase 3 receptor ligand (Flt3L)-based vaccination administered
      with an adenoviral vector prevents tumor growth of colorectal cancer in a BALB/c
      mouse model.
AB  - PURPOSE: Colorectal cancer is the third most frequent cancer in industrial
      nations. Therapeutic strategies to treat metastatic disease and prevent
      recurrence are needed. Anti-tumor immunity can be induced by dendritic cells.
      Dendritic cells can be expanded by the fms-like tyrosine kinase 3 ligand (Flt3L)
      in vivo. The aim of this study was to develop an adenoviral-based immune-gene
      therapy of colorectal cancer with Flt3L in a BALB/c mouse model. METHODS: A new
      Flt3L-encoding adenoviral vector (pAdFlt3L) was administered in two approaches in
      a CT26 colon cancer model in female BALB/c mice. In the therapeutic approach,
      pAdFlt3L was injected into the tail vein or directly into subcutaneous CT26 colon
      carcinoma tumors in BALB/c mice. In the vaccination protocol, mice were
      vaccinated with CT26 cell lysate and pAdFlt3L subcutaneous prior to subcutaneous
      application of vital CT26 cells. RESULTS: Application of pAdFlt3L led to high
      levels of Flt3L in vitro and in vivo. Significant expansion of dendritic cells
      after application of pAdFlt3L in vivo was confirmed by the use of CD11c and CD11b
      surface markers in immunohistochemistry and flow cytometry (p = 0.019). In the
      therapeutic approach, neither intravenous nor intratumoral treatments with
      pAdFlt3L lead to regression of CT26 tumors. In the vaccination protocol,
      vaccination completely prevented tumor growth and resulted in superior survival
      compared to control mice (p < 0.001). CONCLUSIONS: Our results demonstrate that
      immunostimulatory therapy with pAdFlt3L is effective to prevent tumor development
      through vaccination and may represent a therapeutic tool to prevent metastatic
      disease.

PMID- 24114289
TI  - Direct assessment of preferences for social interactions in children with autism.
AB  - Qualitative and quantitative differences in social interactions are core symptoms
      of the autism spectrum disorder (ASD) diagnostic criteria, although there is
      heterogeneity among individuals with ASDs. This study used a concurrent operants
      arrangement to evaluate whether social interactions functioned as positive
      reinforcement, negative reinforcement, or as neutral stimuli for 6 individuals
      with autism. Data suggest that clinicians who work with individuals with ASD
      should ascertain the functional properties of social interactions prior to using
      them as a consequence in interventions. 

PMID- 24114290
TI  - Direct comparison of laser Doppler flowmetry and laser Doppler imaging for
      assessment of experimentally-induced inflammation in human skin.
AB  - OBJECTIVE AND DESIGN: Laser Doppler imaging (LDI) and laser Doppler flowmetry
      (LDF) can measure localized skin perfusion. The purpose of the study was to
      directly compare LDF with LDI as a tool for measuring skin blood changes in an
      experimental model of chemically-induced skin inflammation. METHODS: Regions of
      interest 1.8 cm2 in area on the forearm skin of eight healthy volunteers were
      randomized and exposed to 0.25, 0.5, 1, or 2 % topical sodium lauryl sulfate
      (SLS) or vehicle for 24 h. Mean blood flow was measured by LDI and LDF at 24, 48,
      and 72 h. Inflammation was clinically graded using a standardized, clinical
      score. RESULTS: Sodium lauryl sulfate induced significant, dose-dependent local
      inflammation. Both Doppler methods were significantly correlated with the
      clinical grading (LDF, r = 0.755; LDI, r = 0.836). LDF and LDI showed similar
      significance differences with regard to dose- and time-response patterns compared
      to the vehicle. The absolute and relative LDF and LDI values were significantly
      correlated. CONCLUSIONS: Laser Doppler flowmetry and LDI showed similar dose- and
      time-response relations in irritant-induced inflammatory skin reactions. For the
      assessment of localized skin reactions, LDI possesses no apparent advantages over
      the less expensive LDF method for grading dermal inflammatory reactions.

PMID- 24114288
TI  - Dll4-Notch signaling in regulation of tumor angiogenesis.
AB  - Tumor angiogenesis is a complex process and involves the tight interplay of tumor
      cells, endothelial cells, phagocytes and their secreted factors, which may act as
      promoters or inhibitors of angiogenesis. Many signaling pathways involved in
      these processes such as vascular endothelial growth factor (VEGF), fibroblast
      growth factors, Wnt and mTOR signaling pathway. Though research has confirmed
      that VEGF can play an important role in tumor angiogenesis, and has designed a
      lot of drugs that target VEGF, both experimental and clinical studies showed that
      these pathways mentioned above including VEGF did not play key roles in tumor
      angiogenesis. With the deepening of the research, people find that of all the
      signaling pathways involved in tumor angiogenesis, Notch signaling is the most
      notable one and plays crucial role in tumor angiogenesis. It was previously
      recognized that the Notch signaling plays a key role only in physiological
      angiogenesis such as development, wound healing and pregnancy. However, an
      increasing number of studies have proved that Notch signaling is also involved in
      pathological angiogenesis such as tumor angiogenesis and plays a critical role in
      these processes. More importantly, compared to resistance caused by anti-VEGF or
      other signaling pathways, experimental evidence revealed that Notch was involved
      in anticancer drug resistance, indicating that targeting Notch could be a novel
      therapeutic approach to the treatment for cancer by overcoming drug resistance of
      cancer cells. More recently, research has demonstrated that Notch ligands Delta
      like 4 (Dll4) plays a key role in tumor angiogenesis. Data show that Dll4
      functions as a negative regulator of tumor angiogenesis and is upregulated in
      tumor vasculature. This review focus on recent insights into Dll4-Notch signaling
      in tumor angiogenesis and its mechanisms, which may be utilized for a potential
      pharmacological use as a target for anti-angiogenic cancer therapy. 

PMID- 24114291
TI  - Nebulized epinephrine for croup in children.
AB  - BACKGROUND: Croup is a common childhood illness characterized by barky cough,
      stridor, hoarseness and respiratory distress. Children with severe croup are at
      risk for intubation. Nebulized epinephrine may prevent intubation. OBJECTIVES: To
      assess the efficacy (measured by croup scores, rate of intubation and health care
      utilization such as rate of hospitalization) and safety (frequency and severity
      of side effects) of nebulized epinephrine versus placebo in children with croup,
      evaluated in an emergency department (ED) or hospital setting. SEARCH METHODS: We
      searched CENTRAL 2013, Issue 6, MEDLINE (1966 to June week 3, 2013), EMBASE (1980
      to July 2013), Web of Science (1974 to July 2013), CINAHL (1982 to July 2013) and
      Scopus (1996 to July 2013). SELECTION CRITERIA: Randomized controlled trials
      (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to
      hospital. Comparisons were: nebulized epinephrine versus placebo, racemic
      nebulized epinephrine versus L-epinephrine (an isomer) and nebulized epinephrine
      delivered by intermittent positive pressure breathing (IPPB) versus nebulized
      epinephrine without IPPB. Primary outcome was change in croup score post
      treatment. Secondary outcomes were rate and duration of intubation and
      hospitalization, croup return visit, parental anxiety and side effects. DATA
      COLLECTION AND ANALYSIS: Two authors independently identified potentially
      relevant studies by title and abstract (when available) and examined relevant
      studies using a priori inclusion criteria, followed by methodological quality
      assessment. One author extracted data while the second checked accuracy. We use
      the standard methodological procedures expected by the Cochrane Collaboration.
      MAIN RESULTS: Eight studies (225 participants) were included. In general,
      children included in the studies were young (average age less than two years in
      the majority of included studies). Severity of croup was described as moderate to
      severe in all included studies. Six studies took place in the inpatient setting,
      one in the ED and one setting was not specified. Six of the eight studies were
      deemed to have a low risk of bias and the risk of bias was unclear in the
      remaining two studies.Nebulized epinephrine was associated with croup score
      improvement 30 minutes post-treatment (three RCTs, standardized mean difference
      (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I(2) statistic = 0%).
      This effect was not significant two and six hours post-treatment. Nebulized
      epinephrine was associated with significantly shorter hospital stay than placebo
      (one RCT, MD -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L
      epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33;
      95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant
      reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to
      1.65). There was no significant difference in croup score between administration
      of nebulized epinephrine via IPPB versus nebulization alone at 30 minutes (one
      RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to
      0.42). None of the studies sought or reported data on adverse effects. AUTHORS'
      CONCLUSIONS: Nebulized epinephrine is associated with clinically and
      statistically significant transient reduction of symptoms of croup 30 minutes
      post-treatment. Evidence does not favor racemic epinephrine or L-epinephrine, or
      IPPB over simple nebulization.The authors note that data and analyses were
      limited by the small number of relevant studies and total number of participants
      and thus most outcomes contained data from very few or even single studies.

PMID- 24114293
TI  - Age-related ptosis of the buttock: an anthropometric gender-specific analysis.
AB  - Buttock reshaping has received a lot of attention, although to date there are no
      anthropometric gender-specific datasets to show the aging of the gluteal region
      from infancy to old age to guide surgical planning of gender-specific buttock
      reshaping. To make surgical planning easier, we analyzed the characteristics of
      the aging buttock in 280 volunteers ranging in age from 15 to 85 years and
      classified the age characteristics of the gluteal region into gender-specific
      categories to establish a classification system that could guide surgical
      techniques needed to reshape and rejuvenate the buttock. Based on our
      measurements it was evident that males showed fewer signs of atrophy and less
      ptosis of their buttock with less reduction of the gluteal volume as they aged
      than did females. Based on the results, it is concluded that gender-specific
      surgical rejuvenation of the buttock area should include shortening of the
      gluteal crease, lifting the gluteal mass, adding volume, and smoothening of
      curvature to the lateral sides of the gluteal region. LEVEL OF EVIDENCE IV: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24114294
TI  - Single treatment of grades II and III cellulite using a minimally invasive 1,440
      nm pulsed Nd:YAG laser and side-firing fiber: an institutional review board
      approved study with a 24-month follow-up period.
AB  - BACKGROUND: Cellulite represents one of the common topographic alterations to the
      skin surface and one of the structural changes to the subdermal fat and septal
      band of the posterolateral thighs. Currently, no treatment exists to address this
      entity with a multifactorial genesis that produces long-term beneficial outcomes.
      This clinical study evaluated the safety and efficacy of the 1,440-nm laser and
      the duration of the clinical benefits during 2 years. METHODS: Initially, 25
      healthy women with thigh cellulite were enrolled in this prospective
      institutional review board (IRB)-approved study. For grade II cellulite, the
      laser fiber delivered up to 1,000 J of energy to the undersurface of the entire
      involved skin. For grade III cellulite, the laser fiber distributed 1,300 to
      1,500 J of energy to melt the subdermal fat, subcise the taut septal bands, and
      heat the reticular dermis. Baseline and posttreatment analyses included
      standardized high-resolution photography, skin elasticity measurements,
      ultrasound scanning for dermal thickness, histology, investigator global
      assessment scores, and recording of adverse events. RESULTS: Of the 24 subjects
      who underwent treatment, only 20 were available for the 6-month follow-up
      assessment. Objective measurements at 2 years demonstrated an increase over the
      baseline mean skin elasticity (34 %) and mean dermal thickness (11 %), as well as
      an increase in the average percentage of dermal thickening determined by
      ultrasound imaging. Independent investigator global assessments were rated higher
      for grade II subjects than for grade III subjects throughout the 2-year follow-up
      period. Mild adverse events disappeared by the third month. CONCLUSIONS: This IRB
      conducted clinical trial, as part of a multicenter study for Food and Drug
      Administration approval, demonstrated the safety and efficacy of a single
      minimally invasive treatment for grades II and III thigh cellulite during a 2
      year follow-up period. LEVEL OF EVIDENCE II: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 24114295
TI  - Treatment of irradiated expanders: protective lipofilling allows immediate
      prosthetic breast reconstruction in the setting of postoperative radiotherapy.
AB  - BACKGROUND: Immediate two-stage prosthetic breast reconstruction in the setting
      of postmastectomy radiotherapy (PMRT) currently is hardly achieved with the fast
      track expander exchange proposed by Cordeiro and colleagues or the delayed
      immediate breast reconstruction proposed by Kronowitz and Robb. Each of these
      techniques has important drawbacks and complications. To overcome these problems,
      the authors in 2011 described lipofilling on irradiated expanders in patients
      undergoing unplanned PMRT (Cagliari University Hospital [CUH] protocol) for early
      breast cancers with specific risk factors. The authors report their experience
      after expanding the use of such a protocol for any immediate expander/implant
      reconstruction in a patient undergoing PMRT. METHODS: The timing for advanced
      breast cancer involves immediate reconstruction with a tissue expander, complete
      tissue expansion, radiotherapy (RT) after neoadjuvant chemotherapy starting 2-3
      months after mastectomy, one or two fresh fat-grafting sessions at least 6 weeks
      after RT, and an expander-implant exchange with anterior capsulectomy at least 3
      months after the completion of fat grafting. The timing for early breast cancers
      with specific risk factors involves immediate reconstruction with a tissue
      expander, complete tissue expansion during postoperative chemotherapy, RT 6
      months after mastectomy, one or two fat-grafting sessions 6 weeks after RT, and
      an expander-implant exchange with anterior capsulectomy at least 3 months after
      the completion of fat grafting. From 2008 to 2012, 16 patients undergoing total
      mastectomy and immediate expander-implant breast reconstruction with subsequent
      PMRT were treated according to the CUH protocol. RESULTS: The results have been
      extremely encouraging, with rates of ulceration and implant exposure in the
      radiotreated area dropping to 0 %. These results were retrospectively compared
      with those for a control group of 16 patients who underwent immediate
      implantation of an expander. In this latter group, the extrusion rate of the
      implant in the end was 31.25 %, and this was statistically significant (p <
      0.03). The shape and symmetry also were significantly better in the lipofilled
      patients. CONCLUSION: Protective lipofilling on irradiated expanders appears to
      be a valid technique for avoiding ulceration and implant exposure after PMRT
      while allowing a complete expansion. LEVEL OF EVIDENCE IV: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 24114296
TI  - Immunoexpression of proliferating cell nuclear antigen (PCNA) in spleen of
      splenectomized rats with preservation of inferior pole, submitted to hyperbaric
      oxygenation.
AB  - PURPOSE: To analyze PCNA immunoexpression on the inferior pole of the spleen of
      splenectomized rats submitted to hyperbaric oxygenation (HBO). METHODS: Were
      analyzed fragments of the inferior pole of the spleen of 20 male Wistar rats
      submitted to splenectomy with preservation of the inferior pole. The rats were
      divided in two groups: group A (n=10) without HBO and group B (n=10) submitted to
      HBO at 2, 5 atmospheres per 120 minutes, twice a day for three days and once a
      day for seven days. The groups were then subdivided in four subgroups: A15 (n=5),
      with euthanasia on the 15th day; A45 (n=5), with euthanasia on the 45th day; B15
      (n=5) with euthanasia on the 15th day and B45 with euthanasia on the 45th day.
      Respectively on these days, fragments of the inferior pole of the spleen of all
      animals were collected and analyzed with the immunohistochemistry technique in
      order to evaluate PCNA expression. RESULTS: There was an expressive increase in
      PCNA immunoreactivity in the group B. The 45 day postoperative period resulted in
      a higher level of positivity than the 15 day postoperative period (p<0.01).
      CONCLUSION: The quantitative analysis of proliferating cell nuclear antigen
      positive suggests that hyperbaric oxygenation increases cellular proliferation,
      contributing to splenic regeneration.

PMID- 24114297
TI  - Experimental model for the study of soft tissue fixation methods on skin
      pericranium flaps in rats.
AB  - PURPOSE: To develop an experimental model to study and radiologically monitor
      displacement of skin flaps in the pericranium of rats subjected to traction and
      surgical fixation using suture anchored in a skull bone tunnel or with N-butyl-2
      cyanoacrylate (HistoacrylTM) surgical adhesive. METHODS: Radiological markers
      were placed in the subcutis of Wistar rats undergoing subperiosteal detachment of
      the pericranium with pulling and fixation of the flap. We performed radiography
      on postoperative days 3, 7, 14, 21, and 45. A p-value of <0.05 was considered
      significant. RESULTS: Qualitative analysis of the data indicated that the flaps
      in the surgical adhesive group remained in place with no change from the
      immediate postoperative position. However, the flaps in the suture anchored in
      the skull bone tunnel group and in the control group showed similar healing, with
      a loss of attachment of 9.7% and 22%, respectively, compared with the immediate
      postoperative position. There was no quantitative difference between the groups.
      CONCLUSIONS: This experimental model created acceptable experimental conditions
      for testing different soft tissue fixation methods. The use of tissue fixatives
      contributed to better placement of pericranium-cutaneous flaps, and surgical
      adhesive was superior to suture anchor in the skull bone tunnel for fixation of
      pericranium-cutaneous flaps.

PMID- 24114298
TI  - Does acute alcohol intoxication interfere with colonic anastomosis wound healing?
      A rat model of nondestructive colon trauma.
AB  - PURPOSE: To evaluate the effects of acute alcohol intoxication on healing of
      colonic anastomosis. METHODS: Thirty-six rats were allocated into two groups.
      Animals in the alcohol (A) were given 2 mL of ethanol diluted in 0.9% saline
      solution to a concentration of 40% by gavage immediately before anesthesia,
      whereas control (C) animals received 2 mL of 0.9% saline solution via the same
      route. A colonic anastomosis was then performed in all animals. On postoperative
      days 1, 3, and 7, anastomotic breaking strength was assessed and
      histopathological examination was performed. Change in body weight and mortality
      were also evaluated. RESULTS: The median of anastomotic tensile strength on the
      postoperative day 1 was 0.09 Newtons for group A and 0.13 for group C. (p>0.05).
      The median of anastomotic tensile strength on the postoperative day 3 was 0.13
      Newtons for group A and 0.17 for group C. (p>0.05). The median of anastomotic
      tensile strength on the postoperative day 7 was 0.30 Newtons for group A and 0.35
      for group C. (p>0.05). There was no significant difference between the groups A
      and C, in the first, third or seventh POD (p>0.05), in any of the analyzed
      parameters. There were no statistical differences between groups in the weight.
      Three animals died, all from the group A. CONCLUSION: Acute alcohol intoxication
      did not interfere with wound healing of colonic anastomoses, although it caused
      early postoperative mortality.

PMID- 24114299
TI  - Evaluation of lipoic acid topical application on rats skin wound healing.
AB  - PURPOSE: To evaluate the effects of lipoic acid (thioctic acid) topical
      application on wound healing on rats skin, and the consequences of lipoic acid
      nanoencapsulation on this process. METHODS: The model used was the healing
      activity on wounds induced by surgical incision on rats skin (n = 44). The
      parameters analyzed (11 days) were wound healing rate and histology (vascular
      proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or
      reepithelialization), after application of free lipoic acid or lipoic acid-
      loaded nanocapsules. The antioxidant activity of these formulations was evaluated
      by lipid peroxidation test. RESULTS: It was demonstrated for the first time that
      the topical application of lipoic acid improves wound healing. On the seventh day
      after surgery, the animals treated with lipoic acid showed increased healing rate
      (60.7 +/- 8.4%) compared to the negative control group (43.0 +/- 17.4%), as so
      improvement of histological parameters. The nanoencapsulation reverted the pro
      oxidant activity presented in vitro by lipoic acid, whereas diminished wound
      repair. CONCLUSIONS: The topical application of lipoic acid produced an increase
      in the skin wound healing, which may be related to its pro-oxidant activity. On
      the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant
      activity, although presented minor healing activity.

PMID- 24114300
TI  - Evaluation of the use of raw extract of Euphorbia tirucalli L. in the healing
      process of skin wounds in mice.
AB  - PURPOSE: To evaluate the effects of crude extract of Euphorbia tirucalli in
      cutaneous wound healing. METHODS: A total of 20 Swiss mice were randomly divided
      into two groups, aveloz (GA) and control (CG), and each group was further divided
      into two subgroups based on the deaths scheduled for the 7th and 14th days after
      surgery. The animals underwent a resection of cutaneous fragment with 1cm in
      diameter on the dorsum; the GA was applied in each animal on the subsequent days,
      0.1 mL (30 mg/mL) hydroalcoholic extract of Euphorbia tirucalli was applied on
      the wound, while the same volume of 0.9% saline solution was applied to the GC.
      It was evaluated the lesion diameter and after programmed death, a surgical
      specimen was resected for histopathology. RESULTS: In the macroscopic analysis,
      no statistically significant difference was observed (p = 0.120 and p = 0.186,
      for the 7th and 14th days of death, respectively). The histological evaluation
      revealed no statistically significant difference in the variables acute
      inflammation (p = 0.014) and fibrosis (p = 0.018), when compared the group aveloz
      with the control group on day 14. CONCLUSION: The crude hydroalcoholic extract of
      Euphorbia tirucalli L. demonstrated better outcomes in the healing process, acute
      inflammation and fibrosis on the 14 day postoperatively.

PMID- 24114302
TI  - Sulfane sulfur deficiency in malignant cells, increasing the inhibiting action of
      acetone cyanohydrin in tumor growth.
AB  - PURPOSE: To demonstrate the irreversible poisoning action of the acetone
      cyanohydrin (AC) in malignant cells. METHODS: Thirty male Swiss mice were
      inoculated with 1 x 103 Ehrlich tumor (ET) cells. The mice were divided into
      three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg
      of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were
      euthanized and the number of viable cells in ascites was determined. In the
      meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 MUg/mL). Cell viability
      and percentage of growth inhibition (PGI) were checked after one, two, three,
      four, 18 and 24 hours. RESULTS: There was reduction in volume and number of
      viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not
      present ascites. In ACG2 two mice did not present ascites and in CG none of the
      mice present ascites. The action of AC was dose and time dependent and there was
      no significant difference among the three doses. CONCLUSION: The acetone
      cyanohydrin promoted reduction of the tumor and also prevented tumor development
      in 20% of the treated animals.

PMID- 24114301
TI  - Ponderal behavior of rats fed an omegas 3, 6 and 9 enriched diet submitted to
      colon carcinogenesis induced by azoxymethane.
AB  - PURPOSE: To assess weight changes in rats fed diets with different ratios of
      omegas 3, 6 and 9 submitted to colonic carcinogenesis induced by Azoxymethane
      (AOM). METHODS: Sixty rats with three weeks of life were distributed into five
      groups of specific diets containing 12 animals each: GI- Standard diet without
      administration of AOM, GII- Standard diet with administration of AOM; GIII-
      Hyperlipidic diet with administration of AOM; GIV-Normolipidic diet with
      administration of AOM; GV- Hypolipidic diet with administration of AOM. The
      weight and food intake of each group were assessed four times in each week
      throughout the experiment until euthanasia at 36th week. RESULTS: GI and GII had
      no significant difference in weight. GI showed a significant increase when
      compared to GIII, GIV and GV. GII also showed a significant increase when
      compared to GIII, GIV and GV. When comparing intake of GI as compared to GII no
      significant difference was found, however such groups had higher intake than
      groups III, IV and V. There were found no difference in weight when comparing
      among rats with and without cancer within each groups: GII, GIII, GIV and GV.
      CONCLUSIONS: Diets rich in omega 3, 6 and 9 reduced food intake and weight. Rats
      with colorectal cancer had no decrease in weight as compared to those without
      this condition in the same group.

PMID- 24114303
TI  - Evaluation of nutritional indicators and body composition in patients with
      advanced liver disease enrolled for liver transplantation.
AB  - PURPOSE: Malnutrition is prevalent in patients with advanced liver disease (LD)
      related to multifactorial causes. Fluid retention can underestimate the
      nutritional status based on anthropometric measures. We evaluated nutritional
      indicators and body composition (BC) in patients with liver cirrhosis and
      correlated them with LD severity. METHODS: Forty three patients with LD enrolled
      for liver transplantation were evaluated by Anthropometric measures, subjective
      evaluation (Global Assessment of Nutritional Status - SGA) and biochemical
      indicators. Single-frequency electrical bioimpedance (SFE-BIA) was used to
      evaluate body composition (BC). It measured resistance (R), reactance (Xc) and
      the phase angle (PA). LD severity was estimated by Child-Pugh and Meld criteria
      (Model for End-Stage Liver Disease). RESULTS: Child-Pugh index between patients
      was 7.11 +/- 1.70 and Meld was 12.23 +/- 4.22. Arm Circumference, Arm Muscle
      Circumference and Arm Muscle Area, SGA, hemoglobin, hematocrit and albumin showed
      better correlation with disease severity. Xc and PA showed correlation both with
      Meld and Child-Pugh score when BC were evaluated. PA was depleted in 55.8% of the
      patients. CONCLUSIONS: Diagnosis of malnutrition varied according to the method.
      Global assessment of nutritional status showed better correlation with disease
      severity than with objective methods. Single-frequency electrical bioimpedance
      for body composition analysis in cirrhotic patients must be cautiously used;
      however, primary vectors seems to be valid and promising in clinical practice.

PMID- 24114304
TI  - Intraoperative cholangiography during elective laparoscopic cholecystectomy:
      selective or routine use?
AB  - PURPOSE: To investigate clinical, laboratory and ultrasonographic parameters in
      patients with and without preoperative criteria for intraoperative
      cholangiography (IOC) during laparoscopic cholecystectomy in order to define
      predictive factors of choledocolithiasis. METHODS: As a criterion for inclusion
      in the study the patients should present chronic calculous cholecystitis in the
      presence or absence of any recent clinical, laboratory of ultrasonographic
      finding suggesting choledocolithiasis, who were therefore submitted to
      cholangiography during surgery. RESULTS: A total of 243 laparoscopic
      cholecystectomies with IOC were performed on patients with chronic calculous
      cholecystitis with or without a preoperative formal indication for contrast
      examination. Choledocolithiasis was detected in 33 (13.58%) of the 243 patients
      studied. The incidence of previously unsuspected choledocolithiasis was only one
      case (1.0%) among 100 patients without an indication for this exam. However, 32
      (22.37%) cases of choledocolithiasis were observed among the 143 patients with a
      preoperative indication for IOC. CONCLUSION: The use of selective cholangiography
      is safe for the diagnosis of choledocolithiasis. Only 22.37% of the
      cholangiography results were positive in cases of suspected choledocolithiasis.

PMID- 24114305
TI  - System evaluation on reamed and non-reamed intramedullary nailing in the
      treatment of closed tibial fracture.
AB  - PURPOSE: To systematically evaluate the clinical efficacy of reamed and nonreamed
      intramedullary nailing in treatment of closed tibial fractures with Cochrane
      systematic review methods. METHODS: According to the Cochrane systematic review
      methods, literatures were retrieved from Cochrane library, PubMed, EMbase and
      other database. Randomized controlled trials (RCTs) and quasi-randomized
      controlled clinical trials about reamed and nonreamed intramedullary nailing in
      the treatment of closed tibial fractures were collected and RevMan 5.0 was chosen
      for meta-analysis. RESULTS: A total of seven studies were included in this meta
      analysis. Reamed intramedullary nailing was better than nonreamed intramedullary
      nailing in nonunion rate [P = 0.02, RR = 0.46, 95% CI: (0.24, 0.91)] and implant
      failure rate [P <0.0001, RR = 0.36, 95% CI: (0.22, 0.57)]. No statistically
      significant difference was observed in malunion rate, compartment syndrome rate,
      postoperative infection [P = 0.18, RR = 0.50, 95% CI: (0.18, 1.383); P = 0 43, RR
      = 0.77, 95% CI: (0.40, 1.48); P = 0.27, RR = 0.38, 95% CI: (0.01, 7.87)].
      CONCLUSION: Compared with the nonreamed intramedullary nailing, reamed
      intramedullary nailing can lead to better outcome in the treatment of closed
      tibial fractures.

PMID- 24114307
TI  - Longer GP opening hours would require L2bn shift of funding into primary care,
      says GP leader.

PMID- 24114306
TI  - Clinical score and rapid antigen detection test to guide antibiotic use for sore
      throats: randomised controlled trial of PRISM (primary care streptococcal
      management).
AB  - OBJECTIVE: To determine the effect of clinical scores that predict streptococcal
      infection or rapid streptococcal antigen detection tests compared with delayed
      antibiotic prescribing. DESIGN: Open adaptive pragmatic parallel group randomised
      controlled trial. SETTING: Primary care in United Kingdom. PATIENTS: Patients
      aged >= 3 with acute sore throat. INTERVENTION: An internet programme randomised
      patients to targeted antibiotic use according to: delayed antibiotics (the
      comparator group for analyses), clinical score, or antigen test used according to
      clinical score. During the trial a preliminary streptococcal score (score 1,
      n=1129) was replaced by a more consistent score (score 2, n=631; features: fever
      during previous 24 hours; purulence; attends rapidly (within three days after
      onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN).
      OUTCOMES: Symptom severity reported by patients on a 7 point Likert scale (mean
      severity of sore throat/difficulty swallowing for days two to four after the
      consultation (primary outcome)), duration of symptoms, use of antibiotics.
      RESULTS: For score 1 there were no significant differences between groups. For
      score 2, symptom severity was documented in 80% (168/207 (81%) in delayed
      antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in
      antigen test group). Reported severity of symptoms was lower in the clinical
      score group (-0.33, 95% confidence interval -0.64 to -0.02; P=0.04), equivalent
      to one in three rating sore throat a slight versus moderate problem, with a
      similar reduction for the antigen test group (-0.30, -0.61 to -0.00; P=0.05).
      Symptoms rated moderately bad or worse resolved significantly faster in the
      clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63)
      but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics
      group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score
      group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval
      0.50 to 0.95; P=0.02) and in the antigen test group (58/164) was 27% lower (0.73,
      0.52 to 0.98; P=0.03). There were no significant differences in complications or
      reconsultations. CONCLUSION: Targeted use of antibiotics for acute sore throat
      with a clinical score improves reported symptoms and reduces antibiotic use.
      Antigen tests used according to a clinical score provide similar benefits but
      with no clear advantages over a clinical score alone. TRIAL REGISTRATION:
      ISRCTN32027234.

PMID- 24114308
TI  - MERS coronovirus has probably been present in bats for many years, research
      shows.

PMID- 24114309
TI  - Watchdog advises patients to fight for their rights.

PMID- 24114310
TI  - Dismissing child attachment and discordance for subjective and neuroendocrine
      responses to vulnerability.
AB  - Emerging evidence suggests that as with adults, dismissing children underreport
      their psychological distress relative to physiological indicators of their
      experience (startle response, neural signals). In this report, we extend these
      observations to neuroendocrine reactivity. One hundred and six 8-12-year-old
      children completed the Child Attachment Interview and a computer-based paradigm
      comprised of vignettes reflecting vulnerability in interpersonal contexts.
      Dismissing children's cortisol responses remained comparable from pre-to-post
      paradigm, while secure children's cortisol responses decreased from pre-to-post
      paradigm. Furthermore, compared to secure children, dismissing children reported
      less distress than their cortisol response would suggest. Implications for
      dismissing children's coping and self-regulation are discussed.

PMID- 24114311
TI  - Techniques in electron microscopy of animal tissue.
AB  - Technical improvements in electron microscopy, both instrumental and preparative,
      permit increasingly accurate analyses. Digital images for transmission electron
      microscopy (TEM) can be processed by software programs that automate tasks and
      create custom tools that allow for image enhancement for brightness, contrast and
      coloration; for creation of rectangular, ellipsoidal or irregular area
      selections; and for measurement of mean area and standard deviation. Sample
      preparation remains a source of error since organelles and spatial arrangements
      of macromolecules rapidly change after anoxia. Guidelines for maintaining
      consistency in preparation, examination and interpretation are presented for
      different electron microscopy (EM) modalities. 

PMID- 24114312
TI  - Recovery coefficients determination for partial volume effect correction in
      oncological PET/CT images considering the effect of activity outside the field of
      view.
AB  - OBJECTIVES: The partial volume effect (PVE) has a great impact in quantitative
      PET/CT imaging. Correction methods have been recently proposed by many authors to
      make the image quantification more accurate. This work presents a methodology for
      determining the recovery coefficients (RCs) for PVE correction in PET/CT images.
      It was taken into account the radioactivity outside the field of view (FOV),
      which is expected in a patient image acquisition. METHODS: The NEMA image quality
      phantom and the NEMA scatter phantom were used. The phantoms were filled with
      (18)F-FDG for different sphere-to-background ratios. The RCs have been determined
      from image acquisitions in a Siemens Biograph 16 Hi-Rez PET/CT scanner with and
      without the scatter phantom. RESULTS: The RC values that ranged from 0.38 to 1.00
      without the scatter phantom exhibited a wider variation when this latter was
      taken into account (from 0.27 to 1.02). This more realistic estimation must be
      considered if one takes into account that an incorrect SUV measure in tumors
      leads to errors in the evaluation of the response to therapy based on PET/CT
      images. CONCLUSIONS: The activity outside the FOV should be considered in RCs
      determination to improve the RC-based PVE correction method.

PMID- 24114313
TI  - Utilization patterns and perceptions of playground users in New York City.
AB  - Playgrounds are assumed to be an important resource for physical activity. This
      study investigates seasonal utilization, user preferences, and perceptions of
      safety and upkeep of public playgrounds in New York City. A cross-sectional
      survey was conducted from May 2010 to January 2011 across 10 playgrounds in
      low/middle income neighborhoods in each of the five boroughs in New York City. A
      total of 1,396 adults accompanying children were surveyed. Outcomes included
      playground as main place of outdoor play, and perceptions of playground upkeep
      and safety. Covariates included socio-demographics and other characteristics of
      playground users. Multivariable logistic regression with playground/season fixed
      effects were used. Utilization varied substantially across the four seasons.
      Blacks had higher odds of reporting the playground as the main place of outdoor
      play (AOR 1.78, 95 % CI 1.13-2.80, p < .05). High income users had lower odds of
      reporting the playground as the main place of outdoor play ($60-$80,000: AOR
      0.47, 95 % CI 0.29-0.76, p < .01, $80,000+: AOR 0.47, 95 % CI 0.28-0.79, p <
      .01). Racial differences in perceived upkeep and safety were not significant once
      playground/season fixed effects were included, highlighting the importance of
      neighborhood conditions. Women were more likely to report feeling unsafe within
      playgrounds (AOR 1.51, 95 % CI 1.12-2.02, p < .01). While some playground
      utilization is driven by individual characteristics, perceptions of public
      resources influences utilization and cannot be separated from neighborhood
      conditions. Increasing access to opportunities for physical activity for children
      requires new strategies beyond playground improvements.

PMID- 24114314
TI  - Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch
      syndrome in one local population.
AB  - Germline mutations in DNA mismatch repair (MMR) genes, such as MSH2, cause Lynch
      syndrome, an autosomal dominant predisposition to colorectal as well as other
      cancers. Our research clinic focuses on hereditary colorectal cancer, and over
      the past 9 years we have identified germline mutations in DNA MMR genes in 101
      patients using commercial genetic reference laboratories. We also collected
      samples from twelve patients with absent MSH2 protein expression and
      microsatellite instability in tumor tissue, with a family history suggestive of
      Lynch syndrome, but negative germline test results. The most likely explanation
      for this set of results is that the germline testing did not detect true germline
      mutations in these patients. Two of our patients with failed commercial testing
      were later found to have deletions in the 3' region of EPCAM, the gene just
      upstream of MSH2, but no explanation could be found for inactivation of MSH2 in
      the other ten patients. We used allelic dropout in long PCR to look for potential
      regions of rearrangement in the MSH2 gene. This method detected a potential
      rearrangement breakpoint in the same region of MSH2 where one breakpoint of a 10
      Mb inversion was reported previously. We tested these ten patients for this
      inversion. Six of 10 patients had the inversion, indicating the importance of
      including testing for this inversion in patients suspected of having MSH2-type
      Lynch syndrome in our population. Additionally, this method could be further
      developed to look for inversions in other genes where current methods of testing
      fail to find a causative mutation. 

PMID- 24114315
TI  - RAD51 135G>C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer
      in Serbian women.
AB  - Breast cancer is a complex disease with both genetic and environmental factors
      involved in its etiology. An important role of polymorphisms in genes involved in
      DNA repair has been reported related to breast cancer risk. We conducted a case
      control study in order to investigate the association of RAD51 135G>C and TP53
      Arg72Pro polymorphisms with breast cancer in Serbian women.48 BRCA negative women
      with breast cancer and family history of breast/ovarian cancer (hereditary
      group), 107 women with breast cancer but without family history of the disease
      (sporadic group) and 114 healthy women without a history of the disease (control
      group) were included. Restriction fragment length polymorphism was used for
      genotyping. Genotype and allelic frequencies, the odds ratio (OR) and the 95 %
      confidence interval (CI) were calculated as an estimate of relative risk. The
      Hardy-Weinberg equilibrium was tested using chi(2) test. Significance was
      considered for p < 0.05. RAD51 135G>C showed statistically significant
      association of CC genotype and increased breast cancer risk (OR 10.28, 95 % CI
      1.12-94.5) in hereditary group of patients compared to the control group.
      Regarding the TP53 Arg72Pro, we showed statistical significance for ProPro +
      ProArg comparing to ArgArg (OR 2.34, 95 %, CI 1.17-4.70) in hereditary compared
      to sporadic group. RAD51 135G>C contributes to hereditary breast cancer in
      Serbian population, with CC genotype as a risk factor. We also found that
      carriers of Pro allele of TP53 codon 72 is related to hereditary cancer comparing
      to sporadic one, which indicates it as a potential risk factor for hereditary
      form of disease. 

PMID- 24114316
TI  - Bacterial community compositions of tomato (Lycopersicum esculentum Mill.) seeds
      and plant growth promoting activity of ACC deaminase producing Bacillus subtilis
      (HYT-12-1) on tomato seedlings.
AB  - Study of endophytic bacteria within plant seeds is very essential and meaningful
      on account of their heritability and versatility. This study investigated
      Bacillus bacterial communities within the seeds of four commercial tomato
      varieties, by 16S rRNA gene PCR-RFLP (restriction fragment length polymorphism).
      Phylogenetic analysis of 16S rRNA gene sequences indicated that the 22
      representative isolates belonged to five species of genus Bacillus and the
      bacterial compositions showed remarkable differences among tomato varieties.
      Isolates exhibited multiple plant growth promoting (PGP) traits: 37 % of indole-3
      acetic acid production; 37 % of phosphate solubilization; 24 % of siderophores
      production; 85 % of potential nitrogen fixation and 6 % of 1-aminocyclopropane-1
      carboxylate (ACC) deaminase activity. Isolate HYT-12-1 was shown to have highest
      ACC deaminase activity (112.02 nmol alpha-ketobutyrate mg-1 protein h-1) among
      the five ACC deamiase producing strains. 16S rRNA gene sequencing indicated that
      the isolate HYT-12-1 shared the highest sequence similarity (100 %) with B.
      subtilis. PGP experiments under gnotobiotic and greenhouse conditions revealed
      the ability of strain HYT-12-1 to enhance the growth of tomato seedlings. This is
      the first study to describe endophytic Bacillus communities within tomato seeds,
      and the results suggest that B. subtilis strain HYT-12-1 would have a great
      potential for industrial application as biofertilizer in the future.

PMID- 24114317
TI  - Analysis of biofilm bacterial communities responsible for carbon removal through
      a reactor cascade treating wastewater.
AB  - In this study molecular microbiological and multivariate statistical analyses
      were carried out to determine the structure and dynamics of bacterial communities
      through a biofilm based, pilot-scale wastewater treatment cascade system
      comprised of eight reactors. Results indicated a vertical as well as horizontal
      differentiation of biofilm bacterial communities within individual reactors and
      through the reactor series, respectively. The richness of biofilm samples taken
      from dissolved oxygen rich sections of reactors were relatively lower than of
      samples taken from less oxygenized sections (one-way ANOVA P = 0.07). The
      Euclidean distance based one-way ANOSIM pointed out that in bacteriological point
      of view: (1) no statistically significant difference could be observed among the
      first five reactors (P >= 0.1); (2) the first seven reactors differed
      significantly from the last reactor, (P <= 0.03); (3) reactors 1 and 2 differed
      significantly from reactors 6 and 7 (P ~ 0.02) and (4) reactor 3 from reactor 7
      (P ~ 0.03). 16S rRNA gene cloning revealed that through the cascade system the
      initially dominant heterotrophic bacteria (Acinetobacter, Acidovorax,
      Parabacteroides, Thauera, Desulfobacterium and Desulfomicrobium) were gradually
      replaced or supplemented by autotrophic nitrifying bacteria (Nitrosomonas,
      'Candidatus Nitrotoga' and Nitrospira). Our results indicate that the vertical
      alteration of bacterial community structure within a particular reactor was
      driven by the alteration of dissolved oxygen concentration, while the horizontal
      alteration of bacterial community structure through the cascade system was driven
      mainly by the gradually decreasing dissolved organic matter content and
      increasing dissolved oxygen concentration. 

PMID- 24114318
TI  - The accurate recognition of delirium in the ICU: the emperor's new clothes?

PMID- 24114319
TI  - An attempt to validate the modification of the American-European consensus
      definition of acute lung injury/acute respiratory distress syndrome by the Berlin
      definition in a university hospital.
AB  - PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is
      a new proposal for changing the American-European consensus definition but has
      not been assessed prospectively as yet. In the present study, we aimed to
      determine (1) the prevalence and incidence of ARDS with both definitions, and (2)
      the initial characteristics of patients with ARDS and 28-day mortality with the
      Berlin definition. METHODS: We performed a 6-month prospective observational
      study in the ten adult ICUs affiliated to the Public University Hospital in Lyon,
      France, from March to September 2012. Patients under invasive or noninvasive
      mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end
      expiratory pressure (PEEP) level, and acute onset of new or increased bilateral
      infiltrates or opacities on chest X-ray were screened from ICU admission up to
      discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were
      further classified into specific categories by using the American-European
      Consensus Conference and the Berlin definition criteria. The complete data set
      was measured at the time of inclusion. Patient outcome was measured at day 28
      after inclusion. RESULTS: During the study period 3,504 patients were admitted
      and 278 fulfilled the American-European Consensus Conference criteria. Among
      them, 18 (6.5 %) did not comply with the Berlin criterion PEEP >= 5 cmH2O and 20
      (7.2 %) had PaO2/FiO2 ratio <=200 while on noninvasive ventilation. By using the
      Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n
      = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 %
      for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three
      groups). The incidence of ARDS amounted to 32 per 100,000 population per year,
      with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000
      population per year, respectively (P < 0.05 between the three groups). The 28-day
      mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3
      % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70
      between mild and moderate). In the Cox proportional hazard regression analysis
      ARDS stage was not significantly associated with patient death at day 28.
      CONCLUSIONS: The present study did not validate the Berlin definition of ARDS.
      Neither the stratification by severity nor the PaO2/FiO2 at study entry was
      independently associated with mortality.

PMID- 24114320
TI  - Stability and detergent compatibility of a predominantly beta-sheet serine
      protease from halotolerant B. aquimaris VITP4 strain.
AB  - The present study deals with the characterization of halotolerant protease
      produced by Bacillus aquimaris VITP4 strain isolated from Kumta coast, Karnataka,
      India. The studies were performed at 40  degrees C and pH 8 in Tris buffer. Metal
      ions such as Mn(2+) and Ca(2+) increased the proteolytic activity of the enzyme
      by 34 and 30 %, respectively, at 10 mM concentration. Cu(2+) at 1 mM
      concentration was found to enhance the enzyme activity by 16 %, whereas
      inhibition was observed at higher concentration (>5 mM). Slight inhibition was
      observed even with lower (>1 mM) concentrations of Zn(2+), Hg(2+), Fe(3+),
      Ni(2+), and Co(2+).The activity of protease was completely inhibited by
      phenylmethylsulfonyl fluoride, indicating that the VITP4 protease is a serine
      protease. The presence of ethylenediaminetetraacetic acid and 1,10-phenanthroline
      (>5 mM) moderately inhibited the activity, suggesting that the enzyme is
      activated by metal ions. The protease was purified to homogeneity with a
      purification fold of 15.7 with ammonium sulfate precipitation and 46.65 with gel
      filtration chromatography using Sephadex G-100, resulting in a specific activity
      of 424 +/- 2.6 U mg(-1). The VITP4 protease consists of a single polypeptide
      chain with a molecular mass of 34.7 kDa as determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and matrix-assisted laser
      desorption/ionization-time of flight. Among the different substrates used
      (casein, egg albumin, gelatin, and bovine serum albumin), the activity was higher
      with casein with V max, K m, and k cat values of 0.817 mg ml min(-1), 0.472 mg
      ml(-1), and 2.31 s(-1), respectively. Circular dichroism studies revealed that
      the VITP4 protease has a predominantly beta-sheet structure (51.6 %) with a
      temperature for half denaturation of 85.8  degrees C in the presence of 1 mM
      CaCl2. Additionally, the VITP4 protease was found to retain more than 70 %
      activity in the presence of 10 mM concentration of different detergents (CTAB,
      urea, and sodium dodecyl sulfate) and surfactants (Triton X-100, Tween-20, and
      Tween-80), and the results of wash performance test with various commercial
      detergents confirmed that it can be used in detergent formulations. 

PMID- 24114321
TI  - Purification and characterization of a glucosamine-binding antifungal lectin from
      Phaseolus vulgaris cv. Chinese pinto beans with antiproliferative activity
      towards nasopharyngeal carcinoma cells.
AB  - A lectin has successfully been isolated from Phaseolus vulgaris cv. Chinese pinto
      bean using affinity chromatography, ion exchange chromatography, and gel
      filtration in succession, with a 15.4-fold purification. Investigation of its
      characteristics revealed that Chinese pinto bean lectin (CPBL) was a 58-kDa
      dimeric glucosamine-binding protein. Its Mg(2+)-dependent hemagglutinating
      activity was stable at pH 7-8 and at or below 60  degrees C. When the purified
      lectin was tested against six fungal species including Phyllosticta citriasiana,
      Magnaporthe grisea, Bipolans maydis, Valsa mali, Mycosphaerella arachidicola, and
      Setosphaeria turcica, only the mycelial growth of V. mali was reduced by 30.6 %
      by the lectin at 30 MUM. The lectin did not exert any discernible
      antiproliferative effects on breast cancer MCF-7 cells, but was able to suppress
      proliferation of nasopharyngeal carcinoma HONE-1 cells, with an IC50 of 17.3 MUM,
      as revealed by the MTT assay. Since few plant lectins demonstrate antifungal
      activity against V. mali, and not many others have inhibitory effects on HONE-1
      cells, CPBL is a distinctive lectin which may be exploited for development into
      an agent against V. mali and HONE-1 cells. 

PMID- 24114322
TI  - Superparamagnetic polymer emulsion particles from a soap-free seeded emulsion
      polymerization and their application for lipase immobilization.
AB  - Using emulsion copolymer of styrene (St), glycidyl methacrylate (GMA) and 2
      hydroxyethyl methacrylate (HEMA) as seed latexes, the superparamagnetic polymer
      emulsion particles were prepared by seeded emulsion copolymerization of butyl
      methacrylate (BMA), vinyl acetate (VAc) and ethylene glycol dimethacrylate in the
      presence of the seed latexes and superparamagnetic Fe3O4/SiOx nanoparticles (or
      Fe3O4-APTS nanoparticles) through a two-step process, without addition of any
      emulsifier. The magnetic emulsion particles named P(St-GMA-HEMA)/P(BMA-VAc) were
      characterized by transmission electron microscope and vibrating sample
      magnetometry. The results showed that the magnetic emulsion particles held a
      structure with a thinner shell (around 100 nm) and a bigger cavity (around 200
      nm), and possessed a certain level of magnetic response. The resulting magnetic
      emulsion particles were employed in the immobilization of lipase by two
      strategies to immobilized lipase onto the resulting magnetic composites directly
      (S-1) or using glutaraldehyde as a coupling agent (S-2), thus, experimental data
      showed that the thermal stability and reusability of immobilized lipase based on
      S-2 were higher than that of S-1. 

PMID- 24114324
TI  - Optimal time for initiating antiretroviral therapy (ART) in HIV-infected,
      treatment-naive children aged 2 to 5 years old.
AB  - BACKGROUND: The use of combination antiretroviral therapy (cART) comprising three
      antiretroviral medications from at least two classes of drugs is the current
      standard treatment for HIV infection in adults and children. Current World Health
      Organization (WHO) guidelines for antiretroviral therapy recommend early
      treatment regardless of immunologic thresholds or the clinical condition for all
      infants (less than one years of age) and children under the age of two years. For
      children aged two to five years current WHO guidelines recommend (based on low
      quality evidence) that clinical and immunological thresholds be used to identify
      those who need to start cART (advanced clinical stage or CD4 counts <= 750
      cells/mm(3) or per cent CD4 <= 25%). This Cochrane review will inform the current
      available evidence regarding the optimal time for treatment initiation in
      children aged two to five years with the goal of informing the revision of WHO
      2013 recommendations on when to initiate cART in children. OBJECTIVES: To assess
      the evidence for the optimal time to initiate cART in treatment-naive, HIV
      infected children aged 2 to 5 years. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS
      conference database, specific relevant conferences, www.clinicaltrials.gov, the
      World Health Organization International Clinical Trials Registry platform and
      reference lists of articles. The date of the most recent search was 30 September
      2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared
      immediate with deferred initiation of cART, and prospective cohort studies which
      followed children from enrolment to start of cART and on cART. DATA COLLECTION
      AND ANALYSIS: Two review authors considered studies for inclusion in the review,
      assessed the risk of bias, and extracted data on the primary outcome of death
      from all causes and several secondary outcomes, including incidence of CDC
      category C and B clinical events and per cent CD4 cells (CD4%) at study end. For
      RCTs we calculated relative risks (RR) or mean differences with 95% confidence
      intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from
      adjusted analyses. We combined results from RCTs using a random effects model and
      examined statistical heterogeneity. MAIN RESULTS: Two RCTs in HIV-positive
      children aged 1 to 12 years were identified. One trial was the pilot study for
      the larger second trial and both compared initiation of cART regardless of
      clinical-immunological conditions with deferred initiation until per cent CD4
      dropped to <15%. The two trials were conducted in Thailand, and Thailand and
      Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages
      2 to 5 years were included in this review. There was one death in the immediate
      cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In
      the subgroup analysis of children aged 24 to 59 months, there was one CDC C event
      in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the
      immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In
      this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI
      2.7 to 9.1). One cohort study from South Africa, which compared the effect of
      delaying cART for up to 60 days in 573 HIV-positive children starting
      tuberculosis treatment (median age 3.5 years), was also included. The adjusted
      hazard ratios for the effect on mortality of delaying ART for more than 60 days
      was 1.32 (95% CI 0.55 to 3.16). AUTHORS' CONCLUSIONS: This systematic review
      shows that there is insufficient evidence from clinical trials in support of
      either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5
      years. Programmatic issues such as the retention in care of children in ART
      programmes in resource-limited settings will need to be considered when
      formulating WHO 2013 recommendations.  

PMID- 24114326
TI  - A theoretical investigation into the cooperativity effect between the H???O and
      H???F- interactions and electrostatic potential upon 1:2 (F-:N
      (Hydroxymethyl)acetamide) ternary-system formation.
AB  - The cooperativity effects between the O/N-H???F(-) anionic hydrogen-bonding and
      O/N-H???O hydrogen-bonding interactions and electrostatic potentials in the 1:2
      (F(-):N-(Hydroxymethyl)acetamide (signed as "ha")) ternary systems are
      investigated at the B3LYP/6-311++G** and MP2/6-311++G** levels. A comparison of
      the cooperativity effect in the "F(-)???ha???ha" and "FH???ha(-)???ha" systems is
      also carried out. The result shows that the increase of the H???O interaction
      energy in the O-H???O-H, N-H???O-H or N-H???O = C link is more notable than that
      in the O-H???O = C contact upon ternary-system formation. The cooperativity
      effect is found in the complex formed by the O/N-H???F(-) and O/N-H???O
      interactions, while the anti-cooperativity effect is present in the system with
      only the O/N-H???F(-) H-bond or the "FH???ha(-)???ha" complex by the N(-)???H-F
      contact. Atoms in molecules (AIM) analysis and shift of electron density confirm
      the existence of cooperativity. The most negative surface electrostatic potential
      (V(S,min)) correlates well with the interaction energy E' int.(ha???F-) and
      synergetic energy E(syn.), respectively. The relationship between the change of
      V(S,min) (i.e., DeltaV(S,min)) and E(syn.) is also found.

PMID- 24114325
TI  - Epigenetic choreography of stem cells: the DNA demethylation episode of
      development.
AB  - Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic
      information in eukaryotes. DNA demethylation plays a very significant role during
      embryonic development and stands out for its contribution in molecular
      reconfiguration during cellular differentiation for determining stem cell fate.
      DNA demethylation arbitrated extensive make-over of the genome via reprogramming
      in the early embryo results in stem cell plasticity followed by commitment to the
      principal cell lineages. This article attempts to highlight the sequential phases
      and hierarchical mode of DNA demethylation events during enactment of the
      molecular strategy for developmental transition. A comprehensive knowledge
      regarding the pattern of DNA demethylation during embryogenesis and organogenesis
      and study of the related lacunae will offer exciting avenues for future
      biomedical research and stem cell-based regenerative therapy. 

PMID- 24114328
TI  - Why do people high in self-control eat more healthily? Social cognitions as
      mediators.
AB  - BACKGROUND: Trait self-control and social cognitions both predict dietary
      behaviors, but whether self-control is associated with more beneficial diet
      related cognitions, and the effect of self-control on diet mediated by them, has
      rarely been examined. PURPOSE: We hypothesized that the effect of self-control on
      healthy diet is explained by more proximal diet-related social cognitive factors.
      METHODS: Altogether, 854 military conscripts (age M = 20) completed
      questionnaires on trait self-control and social cognitive factors (self-efficacy,
      outcome expectations, risk perceptions, intentions and planning) upon entering
      the service and a food frequency questionnaire after 8 weeks. RESULTS: Trait self
      control was associated with more positive cognitions regarding healthy diet. The
      mediation hypothesis received support for fruit and vegetable but only partially
      for fast food consumption. CONCLUSION: Individuals high in trait self-control eat
      more healthily because they have higher self-efficacy, more positive taste
      expectations, stronger intentions and more plans, compared to those low in self
      control.

PMID- 24114327
TI  - Interleukin-32beta stimulates migration of MDA-MB-231 and MCF-7cells via the VEGF
      STAT3 signaling pathway.
AB  - BACKGROUND: IL-32 is known to play an important role in inflammatory and
      autoimmune disease responses. In addition to its role in these responses, IL-32
      and its different isoforms have in recent years been implicated in the
      development of various cancers. As of yet, the role of IL-32 in breast cancer has
      remained largely unknown. RESULTS: By performing immunohistochemical assays on
      primary breast cancer samples, we found that the level of IL-32beta expression
      was positively correlated with tumor size, number of lymph node metastases and
      tumor stage. In addition, we found that breast cancer-derived MDA-MB-231 cells
      exogenously expressing IL-32beta exhibited increased migration and invasion
      capacities. These increased capacities were found to be associated with an
      increased expression of the epithelial mesenchymal transition (EMT) markers
      vimentin and Slug, the latter of which is responsible for the increase in
      vimentin transcription. To next investigate whether IL-32beta enhances migration
      and invasion through a soluble factor, we determined the levels of several
      migration-stimulating ligands, and found that the production of VEGF was
      increased by IL-32beta. In addition, we found that IL-32beta-induced VEGF
      increased migration and invasion through STAT3 activation. CONCLUSION: The IL
      32beta-VEGF-STAT3 pathway represents an additional pathway that mediates the
      migration and invasion of breast cancer cells under the conditions of normoxia
      and hypoxia.

PMID- 24114329
TI  - Data science and informatics: when it comes to biomedical data, is there a real
      distinction?

PMID- 24114330
TI  - Biomedical imaging informatics in the era of precision medicine: progress,
      challenges, and opportunities.

PMID- 24114332
TI  - Trypanosoma epinepheli n. sp. (Kinetoplastida) from a farmed marine fish in
      China, the brown-marbled grouper (Epinephelus fuscoguttatus).
AB  - An outbreak of trypanosomosis occurred in farmed Epinephelus fuscoguttatus in
      Xincun Bay, province of Hainan, South China Sea. The infected fish showed loss of
      appetite, lethargy, emaciation, severe anemia, and splenomegaly. Light and
      scanning electron microscopic examination of bloodstream trypomastigotes revealed
      morphological features typical for small-sized marine fish trypanosomes. The
      trypanosome possesses a short body length (mean 22.3 MUm, range 17.6-25.9 MUm)
      and narrow body width (mean1.7 MUm, range 1.3-2.0 MUm), a central nucleus, a
      narrow but distinct undulating membrane, and a relatively long free flagellum
      (mean 10.1 MUm, range 7.4-13.3 MUm). The kinetoplast is situated at approximately
      one quarter of body length from posterior extremity. The division process of this
      trypanosome was observed in the peripheral blood of the host, and occurred by
      transverse constriction at a point between the kinetoplasts. Comparison of the
      small subunit rDNA (SSU rDNA) sequences revealed that the trypanosome from E.
      fuscoguttatus showed 93.4-97.1% identity with the available sequences from
      Trypanosoma spp. from other piscine hosts. Phylogenetic analysis supported the
      existence of an aquatic clade, and the present trypanosome grouped with other
      marine fish trypanosomes, in a subclade together with Trypanosoma senegalense.
      Based on the differences in morphological characteristics, host species, and
      molecular data, the trypanosome infecting E. fuscoguttatus is considered to be a
      new species, for which we propose the name Trypanosoma epinepheli n. sp.

PMID- 24114333
TI  - Differences in placentophagia in relation to reproductive status in the
      California mouse (Peromyscus californicus).
AB  - Parturient females ingest placenta in most mammalian species, whereas fathers may
      do so in species in which both parents provide care for their offspring. To
      determine if the propensity to eat placenta varies with reproductive status in
      the biparental California mouse, we presented placenta to virgin (housed with a
      same-sex pairmate), expectant (pregnant with their first litter), and multiparous
      adult males and females. Liver was presented identically, 3-7 days later, as a
      control. Multiparous females were more likely to eat placenta than expectant and
      virgin females (p-values <0.016), whereas both multiparous and expectant males
      had higher incidences of placentophagia than virgins (p-values <0.016). Liver
      consumption did not differ among groups within either sex. These results suggest
      that propensity to eat placenta increases with maternal/birthing experience in
      females, and with paternal experience and/or cohabitation with a pregnant female
      in males.

PMID- 24114334
TI  - Management of COPD exacerbations in primary care: a clinical cohort study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations are
      associated with lung function decline, lower quality of life, and increased
      mortality, and can be prevented by pharmacological treatment and rehabilitation.
      AIMS: To examine management including examination, treatment, and planned follow
      up of COPD exacerbation visits in primary care patients and to explore how
      measures and management at exacerbation visits are related to subsequent
      exacerbation risk. METHODS: A clinical population of 775 COPD patients was
      randomly selected from 56 Swedish primary healthcare centres. Data on patient
      characteristics and management of COPD exacerbations were obtained from medical
      record review and a patient questionnaire. In the study population of 458
      patients with at least one exacerbation, Cox regression analyses estimated the
      risk of a subsequent exacerbation with adjustment for age and sex. RESULTS:
      During a follow-up period of 22 months, 238 patients (52%) had a second
      exacerbation. A considerable proportion of the patients were not examined and
      treated as recommended by guidelines. Patients with a scheduled extra visit to an
      asthma/COPD nurse following an exacerbation had a decreased risk of further
      exacerbations compared with patients with no extra follow-up other than regularly
      scheduled visits (adjusted hazard ratio 0.60 (95% confidence interval 0.37 to
      0.99), p=0.045). CONCLUSIONS: Guidelines for examination and emergency treatment
      at COPD exacerbation visits are not well implemented. Scheduling an extra visit
      to an asthma/COPD nurse following a COPD exacerbation may be associated with a
      decreased risk of further exacerbations in primary care patients.

PMID- 24114335
TI  - Thyreophagus corticalis as a vector of hypovirulence in Cryphonectria parasitica
      in chestnut stands.
AB  - The natural spread of hypovirulence in Cryphonectria parasitica (Murr.) Barr.
      occurs in chestnut (Castanea sativa Mill) stands and orchards in Italy and other
      European countries, leading to spontaneous recovery of the diseased trees. Little
      is known about how hypovirulence spreads in chestnut stands but various
      corticolous mite species frequently detected on chestnut cankers could be one of
      the many factors playing a role in the spread. Artificial virulent cankers
      created in inoculation field tests and treated with Thyreophagus corticalis
      (Acari, Sarcoptiformes, Acaridae) raised on hypovirulent cultures showed similar
      growth to those treated with mycelia of the hypovirulent strain over 18 months of
      inoculation. Cultures re-isolated from virulent cankers treated with mites were
      found to contain hypovirus like those derived from pairings of virulent and
      hypovirulent strains. Viral dsRNA could be carried externally and/or ingested by
      mites from the hypovirulent mycelia and then transmitted to the mycelia of
      virulent strains, causing their conversion. In a laboratory study, all fecal
      pellets collected from mites reared on hypovirulent and virulent strains grown on
      semi-selective media gave rise to colonies of C. parasitica with similar
      morphological characters and virulence to the original cultures. Field
      inoculation of stump sprouts with the resulting colonies revealed that mite
      digestive tract passage did not alter the virulence of the studied strains. These
      results are of interest for the biological control of chestnut blight.

PMID- 24114336
TI  - Acaricidal activities of bicyclic monoterpene ketones from Artemisia iwayomogi
      against Dermatophagoides spp.
AB  - The acaricidal properties of 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one isolated
      from Artemisia iwayomogi and its structural analogues were evaluated against
      Dermatophagoides farinae and D. pteronyssinus, and their effects were compared
      with that of the commercial acaricide benzyl benzoate. Based on the 50 % lethal
      dose (LD50) values against D. farinae, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one
      (0.82 MUg/cm(2)) was 9.71 times more effective than benzyl benzoate (7.96
      MUg/cm(2)), followed by (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (1.03
      MUg/cm(2)), (1S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (1.58 MUg/cm(2)), and
      (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one oxime (3.05 MUg/cm(2)) in a filter
      paper bioassay. The acaricidal activities of 1,7,7-trimethylbicyclo[2.2.1]heptan
      2-one and its structural analogues against D. pteronyssinus were similar to those
      against D. farinae. These results demonstrate that naturally occurring A.
      iwayomogi-isolated 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one and its structural
      analogues are suitable for the production of natural acaricides against house
      dust mites.

PMID- 24114337
TI  - The impact of insecticides applied in apple orchards on the predatory mite
      Kampimodromus aberrans (Acari: Phytoseiidae).
AB  - Kampimodromus aberrans is an effective predatory mite in fruit orchards. The side
      effects of insecticides on this species have been little studied. Field and
      laboratory experiments were conducted to evaluate the effects of insecticides on
      K. aberrans. Field experiments showed the detrimental effects of etofenprox, tau
      fluvalinate and spinosad on predatory mites. Spider mite (Panonychus ulmi)
      populations reached higher densities on plots treated with etofenprox and tau
      fluvalinate than in the other treatments. Single or multiple applications of
      neonicotinoids caused no detrimental effects on predatory mites. In the
      laboratory, spinosad and tau-fluvalinate caused 100 % mortality. Etofenprox
      caused a significant mortality and reduced fecundity. The remaining insecticides
      did not affect female survival except for imidacloprid. Thiamethoxam,
      clothianidin, thiacloprid, chlorpyrifos, lufenuron and methoxyfenozide were
      associated with a significant reduction in fecundity. No effect on fecundity was
      found for indoxacarb or acetamiprid. Escape rate of K. aberrans in laboratory was
      relatively high for etofenprox and spinosad, and to a lesser extent thiacloprid.
      The use of etofenprox, tau-fluvalinate and spinosad was detrimental for K.
      aberrans and the first two insecticides induced spider mite population increases.
      The remaining insecticides caused no negative effects on predatory mites in field
      trials. Some of them (reduced fecundity and repellence) should be considered with
      caution in integrated pest management programs.

PMID- 24114338
TI  - Single versus multiple enemies and the impact on biological control of spider
      mites in cassava fields in West-Africa.
AB  - To determine whether to use single or multiple predator species for biological
      pest control requires manipulative field experiments. We performed such tests in
      Benin (West Africa) in cassava fields infested by the cassava green mite
      Mononychellus tanajoa, and the cotton red mite Oligonychus gossypii. These fields
      also harboured the cassava apex-inhabiting predator Typhlodromalus aripo and
      either the leaf-inhabiting predator Amblydromalus manihoti or Euseius fustis. We
      manipulated predator species composition on individual plants to determine their
      effect on prey and predator densities. In fields with T. aripo plus A. manihoti,
      M. tanajoa densities were reduced by T. aripo alone or together with A. manihoti,
      but neither of these predators, alone or together, reduced O. gossypii densities.
      In fields with T. aripo plus E. fustis, T. aripo alone or together with E. fustis
      exerted significant control over O. gossypii, but weak control over M. tanajoa.
      Densities of any of the predator species were not affected by co-occurring
      predator species, suggesting a minor role for intraguild predation in the field,
      contrary to earlier experiments on small plants in the laboratory. We conclude
      that (1) T. aripo is the most effective predator species in suppressing M.
      tanajoa, (2) two predator species, T. aripo and E. fustis, are needed to suppress
      O. gossypii, and (3) predator species together on the same plant do not
      negatively affect each other nor the extent to which they control their prey. We
      argue that intraguild predation is reduced due to partial niche separation among
      predator species.

PMID- 24114339
TI  - The effect of herbivore faeces on the edaphic mite community: implications for
      tapeworm transmission.
AB  - Oribatid mites may be of epidemiological and medical importance because several
      species have been shown to serve as intermediate hosts for anoplocephalid
      tapeworms of wild and domestic animals. Despite their economic and conservation
      significance, relatively few studies examined factors influencing the effective
      number of oribatid mites that can serve as intermediate hosts. We examined
      variation in the structure of the edaphic arthropod community in functionally
      different territory parts of the Alpine marmot (Marmota marmota latirostris), a
      known definitive host of a prevalent anoplocephalid tapeworm, Ctenotaenia
      marmotae. We used a field experiment to test whether the abundance of oribatid
      mites in marmot pastures is affected by the presence of fresh herbivore faeces.
      We found that the abundance of soil and litter dwelling oribatid mites in marmot
      pastures did not change shortly after faeces addition. In contrast, numbers of
      other predominant soil-litter and phoretic microarthropods increased after faeces
      addition. The abundance of the two predominant phoretic mites colonizing the
      faeces was inversely related to the abundance of oribatid mites. In contrast, the
      abundance of a ubiquitous soil-litter mesostigmatid mite was a positive function
      of oribatid numbers. Although absolute numbers of oribatid mites did not change
      after faeces addition, our study suggests that, depending on soil quality or
      type, the probability of tapeworm egg ingestion by oribatid mites can be reduced
      due to increased interspecific prey-predatory and trophic interactions. Latrine
      site selection in Alpine marmots is consistent with a reduced probability of
      tapeworm transmission by oribatids.

PMID- 24114340
TI  - Different feeding behaviors in a single predatory mite species. 1. Comparative
      life histories of three populations of Phytoseiulus longipes (Acari:
      Phytoseiidae) depending on prey species and plant substrate.
AB  - The spider mites Tetranychus evansi and T. urticae are key pests of tomato crops,
      for which no sustainable practical control strategy is available yet. A Brazilian
      (B) and an Argentinean (A) population of a phytoseiid predatory mite species,
      Phytoseiulus longipes, are able to develop and reproduce on T. evansi on tomato,
      whereas a Chilean (C) population is not. In order to better characterize the two
      distinct feeding behaviours of these three populations, life table data were
      assessed when the predator was offered T. evansi or T. urticae as prey on bean or
      tomato leaves. No effect of the prey offered nor the plant substrate was
      demonstrated on development durations of the three populations. However, immature
      mortality was low for the Argentinean and the Brazilian populations whatever the
      prey or plant substrate, whereas 89 % of P. longipes from Chile died before
      reaching adulthood when fed T. evansi on tomato. No difference in effect on
      female longevity was detected among the three populations. Finally, the
      demographic parameters of all populations were lower in presence of tomato
      compared to beans. Possible explanations for these results are discussed.

PMID- 24114342
TI  - Species differentiation of scutacarid mites (Heterostigmatina) using multivariate
      morphometric methods.
AB  - The genera of the mite family Scutacaridae (Heterostigmatina) can be easily
      distinguished by certain qualitative traits, whereas the species of these genera
      are lacking conspicuous distinctive features and thus, species descriptions are
      often based on quantitative characters. However, the intraspecific variability of
      these traits can be pronounced and the applicability of multivariate morphometric
      methods for species differentiation has not been studied so far. In the present
      study, four members of the genus Scutacarus, referred to as the acarorum species
      complex, were analysed using traditional and geometric morphometric methods. The
      results showed that multivariate morphometric methods are perfectly suitable for
      differentiating even between morphologically similar scutacarid species, with
      traditional morphometrics performing better than geometric morphometrics. Despite
      their morphological similarity, morphometric analyses support the species status
      of the four members of the species-complex.

PMID- 24114341
TI  - Different feeding behaviours in a single predatory mite species. 2. Responses of
      two populations of Phytoseiulus longipes (Acari: Phytoseiidae) to various prey
      species, prey stages and plant substrates.
AB  - Tritrophic studies involving several populations of the predatory mite
      Phytoseiulus longipes showed distinct life history traits depending on the prey
      offered and/or the plant substrate. In order to better understand the biology of
      this predator, the response to several combinations of prey species (Tetranychus
      evansi and Tetranychus urticae), prey stages (eggs and mobile stages) and plant
      substrates (bean and tomato leaf discs) has been assessed for two populations of
      P. longipes. Unlike what was found for life history traits, both populations
      displayed similar behaviour: they went and stayed more on tomato than on bean,
      they preferred T. urticae over T. evansi and mobile stages over eggs. Combining
      the previous life history data with the present results suggests that P. longipes
      may display host-plant mediated specialization on a prey species, T. evansi.
      Possible underlying mechanisms are discussed, as well as directions for future
      work.

PMID- 24114343
TI  - Retention versus sacrifice of the posterior cruciate ligament in total knee
      arthroplasty for treating osteoarthritis.
AB  - BACKGROUND: The functional and clinical basis on which to choose whether or not
      to retain the posterior cruciate ligament during total knee arthroplasty surgery
      remained unclear after a Cochrane systematic review and meta-analysis in 2005,
      which contained eight clinical trials. Several new trials have been conducted
      since then. Hence, an update of the review was performed. OBJECTIVES: Our aim was
      to assess the benefits and harms of retention compared to sacrifice of the
      posterior cruciate ligament in total knee arthroplasty in patients with
      osteoarthritis of the knee. SEARCH METHODS: An extensive search was conducted in
      CENTRAL, MEDLINE (PubMed), EMBASE, Web of Science, CINAHL, Academic Search
      Premier, Current Contents Connect and Science Direct. All databases were
      searched, without any limitations, up to 6 December 2012. References of the
      articles were checked and citation tracking was performed. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials comparing retention with
      sacrifice of the posterior cruciate ligament in primary total knee arthroplasty
      in patients with osteoarthritis of the knee. DATA COLLECTION AND ANALYSIS: Data
      were collected with a pre-developed form. Risk of bias was assessed independently
      by two authors (WV, LB). The level of evidence was graded using the GRADE
      approach. Meta-analysis was performed by pooling the results of the selected
      studies, when possible. Subgroup analyses were performed for posterior cruciate
      ligament retention versus sacrifice using the same total knee arthroplasty
      design, and for studies using a posterior cruciate ligament retaining or
      posterior stabilised design, and when sufficient studies were available subgroup
      analyses were performed for the same brand. MAIN RESULTS: Seventeen randomised
      controlled trials (with 1810 patients and 2206 knees) were found, described in 18
      articles. Ten of these were new studies compared to the previous Cochrane Review.
      One study from the original Cochrane review was excluded. Most new studies
      compared a posterior cruciate ligament retaining design with a posterior
      stabilised design, in which the posterior cruciate ligament is sacrificed (a
      posterior stabilised design has an insert with a central post which can engage on
      a femoral cam during flexion).The quality of evidence (graded with the GRADE
      approach) and the risk of bias were highly variable, ranging from moderate to low
      quality evidence and with unclear or low risk of bias for most domains,
      respectively.The performance outcome 'range of motion' was 2.4  degrees  higher
      in favour of posterior cruciate ligament sacrifice (118.3  degrees  versus 115.9 
      degrees ; 95% confidence interval (CI) of the difference 0.13 to 4.67; P = 0.04),
      however the results were heterogeneous. On the item 'knee pain' as experienced by
      patients, meta-analysis could be performed on the Knee Society knee pain score;
      this score was 48.3 in both groups, yielding no difference between the groups.
      Implant survival rate could not be meta-analysed adequately since randomised
      controlled trials lack the longer term follow-up in order to evaluate implant
      survival. A total of four revisions in the cruciate-retention and four revisions
      in the cruciate-sacrifice group were found. The well-validated Western Ontario
      and McMaster Universities osteoarthritis index (WOMAC) total score was not
      statistically significantly different between the groups (16.6 points for
      cruciate-retention versus 15.0 points for cruciate-sacrifice). One study reported
      a patient satisfaction grade (7.7 points for cruciate-retention versus 7.9 points
      for cruciate-sacrifice on a scale from 0 to 10, 10 being completely satisfied)
      which did not differ statistically significantly. Complications were distributed
      equally between both groups. Only one study reported several re-operations other
      than revision surgery; that is patella luxations, surgical manipulation because
      of impaired flexion.The mean functional Knee Society Score was 2.3 points higher
      (81.2 versus 79.0 points; 95% CI of the difference 0.37 to 4.26; P = 0.02) in the
      posterior cruciate ligament sacrificing group. Results from the outcome Knee
      Society functional score were homogeneous. All other outcome measures (extension
      angle, knee pain, adverse effects, clinical questionnaire scores, Knee Society
      clinical scores, radiological rollback, radiolucencies, femorotibial angle and
      tibial slope) showed no statistically significant differences between the groups.
      In the subgroup analyses that allowed pooling of the results of the different
      studies, no homogeneous statistically significant differences were identified.
      AUTHORS' CONCLUSIONS: The methodological quality and the quality of reporting of
      the studies were highly variable. With respect to range of motion, pain,
      clinical, and radiological outcomes, no clinically relevant differences were
      found between total knee arthroplasty with retention or sacrifice of the
      posterior cruciate ligament. Two statistically significant differences were
      found; range of motion was 2.4  degrees  higher in the posterior cruciate
      ligament sacrificing group, however results were heterogeneous; and the mean
      functional Knee Society Score was 2.3 points higher in the posterior cruciate
      ligament sacrificing group. These differences are clinically not relevant.

PMID- 24114344
TI  - Dimethoate induces kidney dysfunction, disrupts membrane-bound ATPases and
      confers cytotoxicity through DNA damage. Protective effects of vitamin E and
      selenium.
AB  - Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and
      industry and has toxic effects on non-target organisms especially mammalian.
      However, we still know little about DM-induced kidney injury and its alleviation
      by natural antioxidants. In the present study, selenium (Se), vitamin E, DM,
      Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma
      creatinine and uric acid, kidney MDA, PC, H2O2 and AOPP levels were higher, while
      Na(+)-K(+)-ATPase and LDH values were lower in the DM group than those of
      controls. A smear without ladder formation on agarose gel was shown in the DM
      group, indicating random DNA degradation and DM-induced genotoxicity. A decrease
      in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and
      catalase activities were observed in the DM group when compared to those of
      controls. Plasma cystatin C levels increased, indicating a decrease in glomerular
      filtration rate. When Se or vitamin E was added through diet, the biochemical
      parameters cited above were partially restored in Se+DM and vitamin E+DM than DM
      group. The joint effect of Se and vitamin E was more powerful against DM-induced
      oxidative stress and kidney dysfunction. The changes in biochemical parameters
      were substantiated by histological data. In conclusion, our results indicated a
      possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was
      noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and
      vitamin E ameliorated the toxic effects of this pesticide in renal tissue
      suggesting their role as potential antioxidants.

PMID- 24114345
TI  - Arctigenin exhibits relaxation effect on bronchus by affecting transmembrane flow
      of calcium.
AB  - Arctigenin, a lignan extract from Arctium lappa (L.), exhibits anti-inflammation,
      antioxidation, vasodilator effects, etc. However, the effects of arctigenin on
      bronchus relaxation are not well investigated. This study aimed to investigate
      how arctigenin regulates bronchus tone and calcium ion (Ca(2+)) flow. Trachea
      strips of guinea pigs were prepared for testing the relaxation effect of
      arctigenin to acetylcholine, histamine, KCl, and CaCl2, respectively.
      Furthermore, L-type calcium channel currents were detected by patch-clamp, and
      intracellular Ca(2+) concentration was detected by confocal microscopy. The
      results showed that arctigenin exhibited relaxation effect on tracheae to
      different constrictors, and this was related to decreasing cytoplasmic Ca(2+)
      concentration by inhibiting Ca(2+) influx partly through L-type calcium channel
      as well as promoting Ca(2+) efflux. In summary, this study provides new insight
      into the mechanisms by which arctigenin exhibits relaxation effect on bronchus
      and suggests its potential use for airway disease therapy. 

PMID- 24114346
TI  - Increasing instructional efficiency by presenting additional stimuli in learning
      trials for children with autism spectrum disorders.
AB  - The current study examined the effectiveness and efficiency of presenting
      secondary targets within learning trials for 4 children with an autism spectrum
      disorder. Specifically, we compared 4 instructional conditions using a
      progressive prompt delay. In 3 conditions, we presented secondary targets in the
      antecedent or consequence portion of learning trials, or in the absence of
      prompts and reinforcement. In the fourth condition (control), we did not include
      secondary targets in learning trials. Results replicate and extend previous
      research by demonstrating that the majority of participants acquired secondary
      targets presented in the antecedent and consequent events of learning trials. 

PMID- 24114347
TI  - Lead accumulation and its effects on the branchial physiology of Prochilodus
      lineatus.
AB  - The purpose of this work was to determine the tissue accumulation of lead (Pb)
      and its effects on osmoregulatory processes of the freshwater fish Prochilodus
      lineatus. Juvenile fish were exposed to Pb (from 1.7 to 0.7 mg of dissolved Pb L(
      1)) for 6, 24 and 96 h and Pb accumulation was analyzed in the gills, liver,
      kidneys, blood cells and muscle. The following parameters were also analyzed:
      hematologic (hemoglobin content, hematocrit and number of red blood cells),
      metabolic (blood glucose), endocrine (blood cortisol), osmo ionic (plasma
      osmolality and Na(+), K(+), Cl(-) and Ca(+2) concentrations), gill enzymes
      (Na(+)/K(+)-ATPase and carbonic anhydrase), chloride cell (CC) density and CC
      location in the gills. Pb accumulated in all the analyzed tissues, with the
      kidneys showing the highest concentration, followed by the gills and liver. The
      lowest Pb concentrations were found in blood cells and muscle. Pb promoted an
      increase in blood glucose after 6 and 24 h exposure. Gill Na(+)/K(+)-ATPase was
      inhibited after 24 h of exposure, but its activity was restored at 96 h, probably
      due to the increase in CC in gill lamellae. Plasma Na(+) was reduced after 6 and
      96 h, while K(+) concentrations increased at all the experimental times. Fish
      exposed to Pb showed reduced plasma Ca(+2) at all experimental periods.
      Hematologic parameters remained unchanged. Overall, this study demonstrated that
      Pb interferes in osmoregulatory processes of P. lineatus and the proliferation of
      CC in the gills is a response in order to reestablish adequate ion
      concentrations. 

PMID- 24114348
TI  - Farmer participation in U.S. Farm Bill conservation programs.
AB  - Conservation policy in agricultural systems in the United States relies primarily
      on voluntary action by farmers. Federal conservation programs, including the
      Environmental Quality Incentives Program, offer incentives, both financial and
      technical, to farmers in exchange for adoption of conservation practices.
      Understanding motivations for (as well as barriers to) participation in voluntary
      programs is important for the design of future policy and effective outreach.
      While a significant literature has explored motivations and barriers to
      conservation practice adoption and participation in single programs, few studies
      in the U.S. context have explored general participation by farmers in one place
      and time. A mixed-methods research approach was utilized to explore farmer
      participation in all U.S. Farm Bill programs in Indiana. Current and past program
      engagement was high, with nearly half of survey respondents reporting
      participation in at least one program. Most participants had experience with the
      Conservation Reserve Program, with much lower participation rates in other
      programs. Most interview participants who had experience in programs were
      motivated by the environmental benefits of practices, with incentives primarily
      serving to reduce the financial and technical barriers to practice adoption. The
      current policy arrangement, which offers multiple policy approaches to
      conservation, offers farmers with different needs and motivations a menu of
      options. However, evidence suggests that the complexity of the system may be a
      barrier that prevents participation by farmers with scarce time or resources.
      Outreach efforts should focus on increasing awareness of program options, while
      future policy must balance flexibility of programs with complexity. 

PMID- 24114349
TI  - On individual genome-wide association studies and their meta-analysis.
AB  - Individual genome-wide association (GWA) studies and their meta-analyses
      represent two approaches for identifying genetic loci associated with complex
      diseases/traits. Inconsistent findings and non-replicability between individual
      GWA studies and meta-analyses are commonly observed, hence posing the critical
      question as to how to interpret their respective results properly. In this study,
      we performed a series of simulation studies to investigate and compare the
      statistical properties of the two approaches. Our results show that (1) as
      expected, meta-analysis of larger sample size is more powerful than individual
      GWA studies under the ideal setting of population homogeneity among individual
      studies; (2) under the realistic setting of heterogeneity among individual
      studies, detection of heterogeneity is usually difficult and meta-analysis (even
      with the random-effects model) may introduce elevated false positive and/or
      negative rates; (3) despite relatively small sample size, well-designed
      individual GWA study has the capacity to identify novel loci for complex traits;
      (4) replicability between meta-analysis and independent individual studies or
      between independent meta-analyses is limited, and thus inconsistent findings are
      not unexpected. 

PMID- 24114351
TI  - Stacked multilayers of alternating reduced graphene oxide and carbon nanotubes
      for planar supercapacitors.
AB  - A simple layer-by-layer approach has been developed for constructing 2D planar
      supercapacitors of multi-stacked reduced graphene oxide and carbon nanotubes.
      This sandwiched 2D architecture enables the full utilization of the maximum
      active surface area of rGO nanosheets by using a CNT layer as a porous physical
      spacer to enhance the permeation of a gel electrolyte inside the structure and
      reduce the agglomeration of rGO nanosheets along the vertical direction. As a
      result, the stacked multilayers of rGO and CNTs are capable of offering higher
      output voltage and current production. 

PMID- 24114350
TI  - A genome-wide association study of severe teenage acne in European Americans.
AB  - Despite the family aggregation of severe teenage acne, the genetic basis of this
      common skin condition remains unclear. We conducted a genome-wide association
      study (GWAS) on severe teenage acne in 928 European Americans. The SNP rs4133274
      on chromosome 8q24 (72 kb upstream of MYC) revealed the most significant
      association with severe teenage acne (p value = 1.7 * 10(-6)). The variant allele
      of this SNP (G allele) was associated with an increased risk of severe teenage
      acne with odds ratio of 4.01 (95 % confidence interval = 2.37-6.82). Upon further
      replication, our findings suggest new genetic basis of acne and may explain the
      association between acne and cancer risk observed in the epidemiological studies.

PMID- 24114352
TI  - The effect of thigh muscle activity on anterior knee laxity in the uninjured and
      anterior cruciate ligament-injured knee.
AB  - PURPOSE: The main purpose of this study was to describe the nature of the
      relationship between hamstring muscle activity and anterior knee laxity. METHODS:
      This was a cross-sectional study. Anterior knee laxity was measured at 133N and
      manual maximal forces using the KT2000 knee arthrometer, in 8 ACL-injured and 13
      uninjured individuals. Electromyographic activity of the lateral hamstrings was
      measured during laxity testing. Subjects contracted the hamstrings during
      anterior knee laxity testing at eight predetermined levels of maximal voluntary
      isometric contraction. RESULTS: Volitional contraction of the lateral hamstrings
      reduced anterior knee laxity logarithmically for both the 133N and manual maximal
      tests in both the ACL-injured and uninjured knees. A simple linear regression
      model, with the log of percentage of maximum lateral hamstrings activity as the
      sole predictor, explained approximately 70-80% of the variation in anterior knee
      laxity. Both ACL-injured and uninjured subjects reduced anterior knee laxity at
      the same rate with increases in muscle activity. However, initial lateral
      hamstrings muscle activity had a greater effect on percentage anterior knee
      laxity scores in the ACL-injured as compared to the uninjured knee. CONCLUSIONS:
      Lateral hamstrings activity reduces anterior knee laxity in a nonlinear manner,
      whereby the initial lower level of activation produces the greatest change in
      anterior knee laxity. Therefore, hamstrings muscle activity must be monitored
      during anterior knee laxity testing.

PMID- 24114353
TI  - Assessment of in vivo loading history of the patellofemoral joint: a study
      combining patellar position, tilt, alignment and bone SPECT/CT.
AB  - PURPOSE: The current study investigates whether patella height and tilt or leg
      alignment influence the intensity values as well as the distribution pattern of
      single photon emission computerized tomography/computerized tomography (SPECT/CT)
      tracer uptake in the patellofemoral joint. METHODS: 99mTc-HDP-SPECT/CT and
      radiographs of consecutive 84 knees were prospectively obtained. Lateral
      radiographs were analyzed in terms of patellar height, Insall-Salvati index and
      modified Insall-Salvati index. Skyline views were analyzed for Laurin's lateral
      patellofemoral angle. On long-leg radiographs, the mechanical leg alignment was
      classified as varus, valgus or neutral. SPECT/CT was analyzed for each anatomical
      region using a previously validated SPECT/CT localization and grading algorithm.
      Mean, standard deviation, minimum and maximum of grading for each area of the
      localization scheme were recorded. Nonparametric Spearman's correlations were
      used to correlate patellar height, lateral patellar angle and leg alignment with
      the tracer uptake intensity. Chi-square statistics were used for categorical data
      (p < 0.05). RESULTS: A patella baja correlated significantly with higher SPECT/CT
      tracer uptake in all patellar and lateral femoral regions (p < 0.001). A higher
      lateral patellar tilt correlated significantly with higher tracer uptake in the
      superior lateral femoral parts and the tibial tubercle. In mechanically varus
      aligned knees, there was significantly higher SPECT/CT tracer uptake on the
      medial and in valgus knees on the lateral part of the patellofemoral joint (p <
      0.05). CONCLUSIONS: As the intensity and distribution of the SPECT/CT
      significantly correlated with patella baja and patellar tilt, SPECT/CT might be
      considered as imaging modality for evaluating patients with patellofemoral
      disorders and for follow-up of patients after patellofemoral realignment
      procedures. LEVEL OF EVIDENCE: Diagnostic study, Level II.

PMID- 24114354
TI  - Evolution of C-reactive protein values in the first month after anterior cruciate
      ligament reconstruction: reference values.
AB  - PURPOSE: C-reactive protein (CRP) is often used as an infection marker in
      orthopaedic patients and in particular after anterior cruciate ligament (ACL)
      reconstruction surgery. The aim of this study is to obtain the reference values
      of CRP during the first month after an ACL reconstruction and to analyse the
      epidemiological and surgical parameters that affect these values. METHODS: One
      hundred and twenty ACL reconstructions were included. A CRP determination was
      performed preoperatively and 1, 7, 14, 21 and 28 days after surgery. CRP values
      under 5 mg/l were considered to be normal. RESULTS: One patient developed a
      septic arthritis in the second week postoperatively and was excluded. One hundred
      and seventeen patients [93 males and 24 females; mean age (standard deviation)
      31.6 years (7.6)] underwent 119 ACL reconstructions with different techniques and
      grafts. Preoperative CRP (n = 119) was 1.80 mg/ml (2.6). Mean values at 1, 7, 14,
      21 and 28 days were, respectively, 8.5 mg/ml (11.6), 10.5 mg/ml (17.0), 4.5 mg/ml
      (3.43), 4.4 mg/ml (7.59) and 3.4 mg/ml (3.03). Multivariate analysis showed that
      males had postoperative CRP levels 1.7 higher than females (p < 0.0001; 95 % CI
      1.8-2.5); the patients operated by less experienced surgeons had levels 2.5 times
      higher than those operated by a highly experienced surgeons (p = 0.007; 95 % CI
      1.2-3.4) and that if microfracture of a chondral lesion was associated, the
      levels increased 1.9 times (p = 0.021; 95 % CI 1.1-3.4). CONCLUSIONS: There are
      significant variations in CRP levels after ACL reconstruction in half of patients
      without infectious complications. Males, patients operated by less experienced
      surgeons and those with chondral lesions treated with microfracture had increased
      postoperative CRP levels. CRP values up to five times the normal limit are common
      in the month after an ACL reconstruction and are not necessarily associated with
      infection, especially in these groups.

PMID- 24114355
TI  - Changing grasp position on a wielded object provides self-training for the
      perception of length.
AB  - Calibration of perception to environmental properties typically requires
      experiences in addition to the perceptual task, such as feedback about
      performance. Recently, it has been shown that such experiences need not come from
      an external source or from a different perceptual modality. Rather, in some
      cases, a given perceptual modality can train itself. In this study, we sought to
      expand on the range of experiences in which this can occur for perception of the
      length of a wielded occluded object. Specifically, in two experiments, we
      investigated whether the act of perceiving the length of a wielded object from a
      given grasp position could recalibrate the perception of length from a different
      grasp position. In both experiments, three groups of participants perceived the
      lengths of wielded rods in a pretest, practice, and a posttest. The practice
      included either (a) experimenter feedback, (b) changing the grasp position on the
      object (and again attempting to perceive length), or (c) no additional
      experiences. In Experiment 1, participants changed their grasp position from the
      middle to the end of each rod, and in Experiment 2, they did so from the end to
      the middle of each rod. In both experiments, the results showed that perceiving
      length from a different grasp position can recalibrate (i.e., provide self
      training for) the perception of length. 

PMID- 24114356
TI  - Attentional sampling of multiple wagon wheels.
AB  - Attending to a periodic motion stimulus can induce illusory reversals of the
      direction of motion. This continuous wagon wheel illusion (c-WWI) has been taken
      to reflect discrete sampling of motion information by visual attention. An
      alternative view is that it is caused by adaptation. Here, we attempt to
      discriminate between these two interpretations by asking participants to attend
      to multiple periodic motion stimuli: The discrete attentional sampling account,
      but not the adaptation account, predicts a decrease of c-WWI temporal-frequency
      tuning with set size (with a single periodic motion stimulus the c-WWI is tuned
      to a temporal frequency of 10 Hz). We presented one to four rotating gratings
      that occasionally reversed direction while participants counted reversals. We
      considered reversal overestimations as manifestations of the c-WWI and determined
      the temporal-frequency tuning of the illusion for each set size. Optimal temporal
      frequency decreased with increasing set size. This outcome favors the discrete
      attentional sampling interpretation of the c-WWI, with a sampling rate for each
      individual stimulus dependent on the number of stimuli attended. 

PMID- 24114357
TI  - Conceptualizing the Research Culture in Postgraduate Medical Education:
      Implications for Leading Culture Change.
AB  - By recognizing symbols of research culture in postgraduate medical education,
      educators and trainees can gain a deeper understanding of the existing culture
      and mechanisms for its transformation. First, I identify symbolic manifestations
      of the research culture through a case narrative of a single anesthesia residency
      program, and I offer a visual conceptualization of the research culture. In the
      second part, I theorize the application of Senge's (1994) disciplines of a
      learning organization and discuss leverage for enhancing research culture. This
      narrative account is offered to inform the work of enhancing the broader research
      culture in postgraduate medical education. 

PMID- 24114358
TI  - The impact of being the intermediate caring generation and intergenerational
      transfers on self-reported health of women in Ireland.
AB  - OBJECTIVES: To investigate the associations with being the "sandwich generation"
      in older women in Ireland and its impact on self-reported health. METHODS:
      Analysis of 3,196 women from wave 1 of the Irish Longitudinal Study on Ageing
      (TILDA) was undertaken. Poisson regression was used to determine whether
      intergenerational transfers, were associated with self-rated physical health and
      depression, when controlling for other socio-demographic variables. RESULTS:
      Multivariate analysis found that women in the sandwich generation who financially
      supported their children had better self-rated physical health (poor/fair health
      relative to excellent; RR 0.84, 95 % CI 0.72-0.97). Conversely, the women who
      provided other care for their children showed evidence of poorer mental health
      (case-level depression, RR 1.35, 95 %CI 1.05-1.73). Providing financial support
      for parents was associated with case-level depression (RR 2.21, 95 %CI 1.26
      3.86). CONCLUSIONS: Supporting two generations was associated with both better
      self-rated health and poorer mental health, depending on the type and direction
      of the transfers. This generation of women have substantial caring
      responsibilities. Strategies to address the stresses associated with bi
      directional intergenerational transfers are needed.

PMID- 24114359
TI  - Automated CT scan scores of bronchiectasis and air trapping in cystic fibrosis.
AB  - BACKGROUND: Computer analysis of high-resolution CT (HRCT) scans may improve the
      assessment of structural lung injury in children with cystic fibrosis (CF). The
      goal of this cross-sectional pilot study was to validate automated, observer
      independent image analysis software to establish objective, simple criteria for
      bronchiectasis and air trapping. METHODS: HRCT scans of the chest were performed
      in 35 children with CF and compared with scans from 12 disease control subjects.
      Automated image analysis software was developed to count visible airways on
      inspiratory images and to measure a low attenuation density (LAD) index on
      expiratory images. Among the children with CF, relationships among automated
      measures, Brody HRCT scanning scores, lung function, and sputum markers of
      inflammation were assessed. RESULTS: The number of total, central, and peripheral
      airways on inspiratory images and LAD (%) on expiratory images were significantly
      higher in children with CF compared with control subjects. Among subjects with
      CF, peripheral airway counts correlated strongly with Brody bronchiectasis scores
      by two raters (r=0.86, P<.0001; r=0.91, P<.0001), correlated negatively with lung
      function, and were positively associated with sputum free neutrophil elastase
      activity. LAD (%) correlated with Brody air trapping scores (r=0.83, P<.0001;
      r=0.69, P<.0001) but did not correlate with lung function or sputum inflammatory
      markers. CONCLUSIONS: Quantitative airway counts and LAD (%) on HRCT scans appear
      to be useful surrogates for bronchiectasis and air trapping in children with CF.
      Our automated methodology provides objective quantitative measures of
      bronchiectasis and air trapping that may serve as end points in CF clinical
      trials.

PMID- 24114361
TI  - Blocking autophagy enhances the apoptosis effect of bufalin on human
      hepatocellular carcinoma cells through endoplasmic reticulum stress and JNK
      activation.
AB  - Bufalin extracts are a part of traditional Chinese medicine, Chansu. In the
      current study, we investigated the effect of bufalin on the proliferation of the
      human hepatocellular carcinoma (HCC) cell lines, Huh-7 and HepG-2, and explored
      the therapeutic potential of the drug. Our results demonstrated that bufalin
      markedly inhibited cell proliferation and promoted apoptosis in the Huh-7 and
      HepG-2 cells in vitro. The underlying mechanism of the bufalin-induced apoptosis
      was the induction of endoplasmic reticulum (ER) stress via the IRE1-JNK pathway.
      In addition, during the ER stress response, the autophagy pathway, characterized
      by the conversion of LC3-I to LC3-II, was activated, resulting in increased
      Beclin-1 protein levels, decreased p62 expression and stimulation of autophagic
      flux. Our data supported the pro-survival role of bufalin-induced autophagy when
      the autophagy pathway was blocked with specific chemical inhibitors; the
      involvement of the IRE1 pathway in the ER stress-induced autophagy was also
      demonstrated when the expression of IRE1 and CHOP was silenced using siRNA. These
      data indicate that combining bufalin with a specific autophagy inhibitor could be
      a promising therapeutic approach for the treatment of HCC. 

PMID- 24114360
TI  - The MEK/ERK pathway is the primary conduit for Borrelia burgdorferi-induced
      inflammation and P53-mediated apoptosis in oligodendrocytes.
AB  - Lyme neuroborreliosis (LNB) affects both the central and peripheral nervous
      systems. In a rhesus macaque model of LNB we had previously shown that brains of
      rhesus macaques inoculated with Borrelia burgdorferi release inflammatory
      mediators, and undergo oligodendrocyte and neuronal cell death. In vitro analysis
      of this phenomenon indicated that while B. burgdorferi can induce inflammation
      and apoptosis of oligodendrocytes per se, microglia are required for neuronal
      apoptosis. We hypothesized that the inflammatory milieu elicited by the bacterium
      in microglia or oligodendrocytes contributes to the apoptosis of neurons and
      glial cells, respectively, and that downstream signaling events in NFkB and/or
      MAPK pathways play a role in these phenotypes. To test these hypotheses in
      oligodendrocytes, several pathway inhibitors were used to determine their effect
      on inflammation and apoptosis, as induced by B. burgdorferi. In a human
      oligodendrocyte cell line (MO3.13), inhibition of the ERK pathway in the presence
      of B. burgdorferi markedly reduced inflammation, followed by the JNK, p38 and
      NFkB pathway inhibition. In addition to eliciting inflammation, B. burgdorferi
      also increased total p53 protein levels, and suppression of the ERK pathway
      mitigated this effect. While inhibition of p53 had a minimal effect in reducing
      inflammation, suppression of the ERK pathway or p53 reduced apoptosis as measured
      by active caspase-3 activity and the TUNEL assay. A similar result was seen in
      primary human oligodendrocytes wherein suppression of ERK or p53 reduced
      apoptosis. It is possible that inflammation and apoptosis in oligodendrocytes are
      divergent arms of MAPK pathways, particularly the MEK/ERK pathway. 

PMID- 24114362
TI  - Perturbation of apoptosis upon binding of tRNA to the heme domain of cytochrome
      c.
AB  - In response to apoptotic stimuli, cytochrome c, an inter-membrane space protein
      is released from mitochondria to activate the cascade of caspases that leads to
      apoptosis. Recent evidence suggests that cytochrome c interacts with tRNA in the
      cytoplasm and this interaction was shown to inhibit the caspase mediated
      apoptotic process. Interestingly, cytochrome c does not contain any putative RNA
      binding domain. In this report, we sought to define the structural component of
      cytochrome c that is involved in binding of tRNA. By using gel mobility shift
      assays, we show that holocytochrome c can interact with tRNA but not
      apocytochrome c that lacks the heme domain suggesting that heme is essential for
      the interaction of cytochrome c to tRNA. In addition, using in vitro cross
      linking and circular dichroism spectroscopic studies, we show that cytochrome c
      can undergo heme mediated oligomerization. Prevention of heme mediated
      oligomerization of cytochrome c by potassium ferricyanide treatment prevents the
      binding of tRNA and promotes caspase activation. Our studies provide a novel
      regulation of apoptosis by heme dependent tRNA interaction to cytochrome c. 

PMID- 24114363
TI  - Role of DAPK in neuronal cell death.
AB  - Neuronal cell death happens as a result of the normal physiological process that
      occurs during development, or as part of the pathological process that occurs
      during disease. Death-associated protein kinase (DAPK) is an intracellular
      protein that mediates cell death by its serine/threonine kinase activity, and
      transmits apoptotic cell death signals in various cells, including neurons. DAPK
      is elevated in injured neurons in acute models of injury such as ischemia and
      seizure. The absence of DAPK has been shown to protect neurons from a wide
      variety of acute toxic insults. Moreover, DAPK also regulates neuronal cell death
      during central nervous system development. Neurons are initially overproduced in
      the developing nervous system, following which approximately one-half of the
      original cell population dies. This "naturally-occurring" or "programmed" cell
      death is essential for the construction of the developing nervous system. In this
      review, we focus on the role of DAPK in neuronal cell death after neuronal
      injury. The participation of DAPK in developmental neuronal death is also
      explained. 

PMID- 24114364
TI  - Perceptual narrowing in the context of increased variation: Insights from
      bilingual infants.
AB  - Human infants become native-language listeners through a process of perceptual
      narrowing. Monolingual infants are initially sensitive to a wide range of
      language-relevant contrasts. However, as they mature and gain native-language
      experience, their sensitivity to nonnative contrasts declines. Here, we consider
      the case of infants growing up bilingual as a window into how increased variation
      affects early perceptual development. These infants encounter different
      meaningful contrasts in each of their languages, and must also attend to
      contrasts that occur between their languages. Bilingual infants share many
      classic developmental patterns with monolinguals. However, they also show unique
      developmental patterns in the perception of native distinctions such as U-shaped
      trajectories and dose-response relationships, and show some enhanced sensitivity
      to nonnative distinctions. Analogous developmental patterns can be observed in
      individuals exposed to two nonlinguistic systems in domains such as music and
      face perception. Some preliminary evidence suggests that bilingual individuals
      might retain more sensitivity to nonnative contrasts, reaching a less narrow end
      state than monolinguals. Nevertheless, bilingual infants do become perceptually
      specialized native listeners to both of their languages, despite increased
      variation and differing patterns of perceptual development in comparison to
      monolinguals.

PMID- 24114365
TI  - Profound plasmacytosis in a patient with dengue.

PMID- 24114366
TI  - Factors influencing surgeons' intraoperative leadership: video analysis of
      unanticipated events in the operating room.
AB  - BACKGROUND: The achievement of surgical goals and the successful functioning of
      operating room (OR) teams are dependent on leadership. The attending surgeon is a
      team leader during an operation, with responsibility for task accomplishment by
      the clinical team. This study examined surgeons' leadership behaviors during
      surgical procedures, with particular reference to the effect of intraoperative
      events on leadership. METHODS: Videos of operations (n = 29) recorded at three UK
      teaching hospitals were analyzed to identify and classify surgeons'
      intraoperative leadership behaviors using the Surgeons' Leadership Inventory. The
      frequency and type of leadership behaviors were compared before and after the
      point of no return (PONR) (n = 24), and during an unexpected intraoperative event
      (n = 5). RESULTS: Most of the surgeons' leadership behaviors were directed toward
      the resident during an operation. No significant differences were found for the
      overall number or type of leadership behaviors pre- and post-PONR. The frequency
      of leadership behaviors classified as "Training" and "Supporting others"
      significantly decreased during an unanticipated intraoperative event. DISCUSSION:
      Overall, surgeons engaged in the same leadership behaviors throughout the course
      of an operation unless they were dealing with an unanticipated event. Surgeons
      appeared to adopt a "one size fits all" leadership style approach regardless of
      the team or situation. Additionally, surgeons seemed to limit their
      intraoperative leadership focus to other surgeons rather than to the wider OR
      team.

PMID- 24114367
TI  - Preoperative education in cholecystectomy in the context of a multimodal protocol
      of perioperative care: a randomized, controlled trial.
AB  - BACKGROUND: Preoperative education is a key point in multimodal protocols of
      perioperative care. We investigated whether preoperative education for patients
      undergoing open cholecystectomy would reduce the incidence of perioperative
      symptoms. METHODS: This was a randomized, single-blinded, clinical trial that
      included adult (18-65 years old) candidates for elective open cholecystectomy.
      All patients took part in the ERAS/ACERTO protocol of perioperative care except
      that only the intervention group received preoperative education. The main
      endpoints of the study were the presence and intensity of postoperative symptoms
      (e.g., nausea, vomiting, pain) measured by a visual analogue scale, 24 h after
      the operation. RESULTS: A total of 74 patients (34 in the intervention group, 40
      in the control group) completed the study. The intervention group had
      significantly lower median (interquartile range) scores for nausea [0 (4) vs. 2.5
      (5.8), p = 0.04] and pain [0.2 (2.3) vs. 3.1 (3.45), p < 0.01] than the controls.
      High well-being (score >= 6) was reported by 79.4 % (27 patients) of the
      intervention group in contrast to 57.5 % (23 patients) of the controls (p =
      0.04). CONCLUSIONS: Preoperative education is highly effective in the context of
      a multimodal protocol for enhancing the recovery of patients submitted to open
      cholecystectomy.

PMID- 24114368
TI  - HER2 expression in carcinomas of the true cardia (Siewert type II esophagogastric
      junction carcinoma).
AB  - OBJECTIVES: To evaluate the HER2 status in patients with Siewert type II
      esophagogastric junction carcinoma. BACKGROUND: Trastuzumab is now approved for
      use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive
      unresectable metastatic gastric or esophagogastric junction (EGJ) carcinoma.
      Several studies have evaluated HER2 status in EGJ carcinoma, but none has
      addressed the implication of HER2 positivity in patients with Siewert type II EGJ
      carcinoma. METHODS: We retrospectively evaluated the frequency of HER2 positivity
      in a large single-center cohort of 208 patients with Siewert type II tumors. The
      relations between HER2 expression and the outcomes and other clinicopathologic
      features were examined. RESULTS: Overall, 18.2 % (38/208) of patients in our
      cohort had HER2-positive tumors. HER2 positivity was associated only with
      differentiated carcinomas. The 5-year overall survival (OS) rate was 58.7 %. The
      5-year OS rates in the patient groups with HER2-negative and HER2-positive tumors
      were 61.2 and 48.5 %, respectively. There was no significant difference between
      the groups. Recurrence in the liver was observed in 23.7 % patients of the HER2
      positive group and 7.6 % patients of the HER2-negative group. Multivariate
      analysis to identify the risk factors for liver recurrence revealed only HER2
      positivity (p = 0.0155) as an independent predictive factor. CONCLUSIONS: HER2
      positivity is a powerful predictor of liver recurrence in patients with Siewert
      type II EGJ carcinoma. Use of trastuzumab in combination with chemotherapy in an
      adjuvant setting can be a potentially useful therapeutic strategy to prevent
      hepatic recurrence in patients with resectable EGJ adenocarcinoma showing HER2
      overexpression.

PMID- 24114369
TI  - The impact of functional limitations on long-term outcomes among African-American
      and white women with breast cancer: a cohort study.
AB  - OBJECTIVES: We examined the impact of functional limitations and functional
      decline during the first year following breast cancer diagnosis on the risk of
      mortality from breast cancer and other causes among African-American and white
      women, respectively. DESIGN: The Health and Functioning in Women (HFW) cohort
      study. SETTING: Detroit, Michigan, USA. PARTICIPANTS: A total of 162 African
      American and 813 white women aged 40-84 years with newly diagnosed breast cancer
      identified through the Metropolitan Detroit Cancer Surveillance System over a 7
      month period between 1984 and 1985 and followed for up to 28 years (median 11
      years). OUTCOME MEASURES: Risk of mortality from breast cancer and other causes.
      RESULTS: Statistically significant increases in the risk of other-cause mortality
      were found for each unit increase in the number of self-reported functional
      limitations (HR=1.08, 95% CI 1.03 to 1.14), 0 vs >=1 functional limitations
      (HR=1.47, 95% CI 1.13 to 1.91), difficulty in pushing or pulling large objects
      (HR=1.34, 95% CI 1.04 to 1.73), writing or handling small objects (HR=1.56, 95%
      CI 1.00 to 2.44), and walking half a mile (HR=1.60, 95% CI 1.19 to 2.14).
      Functional limitations and functional decline did not explain racial disparities
      in the survival of this cohort. Functional decline was associated with increased
      risk of other-cause mortality in women with regional and remote disease but not
      in women with localised disease. Whereas measures of functional limitation were
      not associated with breast cancer-specific mortality, each unit of functional
      decline (HR=1.17, 95% CI 1.05 to 1.31) and decline in the ability to sit >=1 h
      (HR=2.06, 95% CI 1.13 to 3.76) were associated with increased risk of breast
      cancer-specific mortality. Measures of functional decline were associated with
      increased risk of breast cancer mortality in overweight and obese women, but not
      in women of normal weight. CONCLUSIONS: Whereas functional limitations were
      associated with increased risk of other-cause mortality, functional decline was
      associated with increased risk of breast cancer mortality.

PMID- 24114370
TI  - The effects of a mindfulness-based lifestyle programme for adults with
      Parkinson's disease: protocol for a mixed methods, randomised two-group control
      study.
AB  - INTRODUCTION: Parkinson's disease (PD) is the second most common
      neurodegenerative disorder in developed countries. There is an increasing
      interest in the use of mindfulness-related interventions in the management of
      patients with a chronic disease. In addition, interventions that promote personal
      control, stress-management and other lifestyle factors, such as diet and
      exercise, assist in reducing disability and improving quality of life in people
      with chronic illnesses. There has been little research in this area for people
      with PD. METHODS: A prospective mixed-method randomised clinical trial involving
      community living adults with PD aged <76 years and with moderate disease severity
      (Hoehn and Yahr stage 2) PD. Participants will be randomised into the ESSENCE 6
      week programme or a matched wait list control group. ESSENCE is a multifaceted,
      healthy lifestyle and mindfulness programme designed to improve quality of life.
      We aim to determine whether participation in a mindfulness and lifestyle
      programme could improve PD-related function and explore self-management related
      experiences and changing attitudes towards self-management. The outcome measures
      will include 5 self-administered questionnaires: PD function and well-being
      questionnaire (PDQ39), Health Behaviours, Mental health, Multidimensional locus
      of control, and Freiburg mindfulness inventory. An embedded qualitative protocol
      will include in-depth interviews with 12 participants before and after
      participation in the 6-week programme and a researcher will observe the programme
      and take notes. ANALYSIS: Repeated measures of Analysis of Variance (ANOVA) will
      examine the outcome measures for any significant effects from the group
      allocation, age, sex, adherence score and attendance. Qualitative data will be
      analysed thematically. We will outline the benefits of, and barriers to, the
      uptake of the intervention. ETHICS: This protocol has received ethics approval
      from the Monash University Human Research Ethics Committee project number
      CF11/2662-2011001553. DISSEMINATION: This is the first research of its kind in
      Australia involving a comprehensive, lifestyle-based programme for people with PD
      and has the potential to involve a broader range of providers than standard care.
      The findings will be disseminated through peer reviewed journals, primary care
      conferences in Australia as well as abroad and through the Parkinson's community.
      REGISTRATION DETAILS: Australian New Zealand Clinical Trials Registry (ANZCTR)
      ACTRN12612000440820.

PMID- 24114371
TI  - Drugs causing adverse events in patients aged 45 or older: a randomised survey of
      Australian general practice patients.
AB  - OBJECTIVE: To determine prevalence of adverse drug events (ADEs) in patients aged
      45 years or older presenting to Australian general practitioners (GPs) and
      identify drug groups related to ADEs, their severity and manifestation. DESIGN:
      Substudy of the Bettering the Evaluation and Care of Health continuous survey of
      Australian GP clinical activity in which randomly selected GPs collected survey
      data from patients. Data are reported with 95% CIs. SETTING: General practice in
      Australia. MAIN OUTCOME MEASURES: Prevalence in the preceding 6 months, type,
      implicated drugs, severity (including hospitalisation) and manifestation of ADEs.
      PARTICIPANTS: From three survey samples, January-October 2007, and two samples,
      January-March 2010, responses were received from 482 GPs about 7561 patients aged
      45 years or older. RESULTS: Of a final sample of 7518 patients (after duplicate
      patients removed), 871 (11.6%) reported ADEs in the previous 6 months. The type
      of ADE was recognised side effect (75.8%, 95% CI 72.0 to 79.7), drug sensitivity
      (9.9%, 95% CI 7.2 to 12.7) and drug allergy (7.4%, 95% CI 4.7 to 10.1). Drug
      interaction (1.0%, 95% CI 0.1 to 1.8), overdose (0.8%, 95% CI 0.0 to 1.5) and
      contraindications (0.2%, 95% CI 0.0 to 0.6) were very infrequent. A severity
      rating was provided for 846 patients. Almost half (45.9%, 95% CI 42.0 to 49.7)
      were rated as 'mild' events, 42.2% (95% CI 38.8 to 45.6) 'moderate', 11.8% (95%
      CI 9.5 to 14.1) severe and 5.4% (95% CI 3.8 to 7.0) had been hospitalised as a
      result of the most recent ADE. Thirteen commonly prescribed drug groups accounted
      for 58% of all ADEs, opioids being the group most often implicated. CONCLUSION:
      ADEs in patients aged 45 or older are frequent and are associated with
      significant morbidity. Most of ADEs result from commonly prescribed drugs at
      therapeutic dosage. The list of causative agents bears little relationship to
      published lists of 'inappropriate medications'.

PMID- 24114372
TI  - Validity of AHRQ patient safety indicators derived from ICD-10 hospital discharge
      abstract data (chart review study).
AB  - OBJECTIVE: To assess if the Agency for Healthcare Research and Quality  patient
      safety indictors (PSIs) could be used for case findings in the International
      Classification of Disease 10th revision (ICD-10) hospital discharge abstract
      data. DESIGN: We identified and randomly selected 490 patients with a foreign
      body left during a procedure (PSI 5-foreign body), selected infections (IV site)
      due to medical care (PSI 7-infection), postoperative pulmonary embolism (PE) or
      deep vein thrombosis (DVT; PSI 12-PE/DVT), postoperative sepsis (PSI 13
      sepsis)and accidental puncture or laceration (PSI 15-laceration) among patients
      discharged from three adult acute care hospitals in Calgary, Canada in 2007 and
      2008. Their charts were reviewed for determining the presence of PSIs and used as
      the reference standard, positive predictive value (PPV) statistics were
      calculated to determine the proportion of positives in the administrative data
      representing 'true positives'. RESULTS: The PPV for PSI 5-foreign body was 62.5%
      (95% CI 35.4% to 84.8%), PSI 7-infection was 79.1% (67.4% to 88.1%), PSI 12
      PE/DVT was 89.5% (66.9% to 98.7%), PSI 13-sepsis was 12.5% (1.6% to 38.4%) and
      PSI 15-laceration was 86.4% (75.0% to 94.0%) after excluding those who presented
      to the hospital with the condition. CONCLUSIONS: Several PSIs had high PPV in the
      ICD administrative data and are thus powerful tools for true positive case
      finding. The tools could be used to identify potential cases from the large
      volume of admissions for verification through chart reviews. In contrast, their
      sensitivity has not been well characterised and users of PSIs should be cautious
      if using them for 'quality of care reporting' presenting the rate of PSIs because
      under-coded data would generate falsely low PSI rates.

PMID- 24114373
TI  - Correlation of chronic renal dysfunction and albuminuria with severity of
      coronary artery lesions in patients with coronary artery disease.
AB  - This study was conducted to investigate the possible correlation of chronic renal
      dysfunction and albuminuria with the severity of coronary artery lesions in
      patients with coronary artery disease (CAD). Two-hundred and ninety-nine patients
      who had undergone coronary angiography for suspected CAD were stratified into
      three groups according to the glomerular filtration rate (GFR): group I included
      144 patients with normal renal function GFR >90 ml/(min * 1.73 m(2)), group II
      included 97 patients with mild renal impairment GFR 60-89 ml/(min * 1.73 m(2)),
      and group III included 58 patients with moderate renal impairment GFR <60 ml/(min
      * 1.73 m(2)). Patients were then stratified into two groups according to the
      albuminuria level (0; minimal, 1+, 2+, 3+): the albuminuria negative group
      (negative = 0) included 171 patients and the albuminuria positive group (positive
      = minimal, 1+, 2+, 3+) included 128 patients. Clinical features and coronary
      lesion characteristics were compared among these groups. Patients with more
      severe renal dysfunction and positive albuminuria had a higher incidence of CAD
      (66.7 vs. 70.1 vs. 72.4%, p = 0.025 and 64.2 vs. 75.0%, p = 0.032), more multi
      vessel disease (31.2 vs. 41.2 vs. 53.4 %, p = 0.004 and 33.3 vs. 46.1%, p =
      0.015), more left anterior descending branch lesions (50.7 vs. 56.7 vs. 60.3%, p
      = 0.012 and 49.1 vs. 61.7 %, p = 0.009), and a higher Gensini score (42.3 +/-
      14.7 vs. 46.1 +/- 19.9 vs. 52.8 +/- 21.2, p = 0.026 and 44.0 +/- 16.0 vs. 50.5 +/
      20.2, p = 0.017). In conclusion, chronic renal dysfunction and albuminuria may
      be important factors determining the occurrence and the severity of CAD.
      Albuminuria was an especially significant indicator at the early stage of renal
      dysfunction.

PMID- 24114374
TI  - Teaching "How?" mand-for-information frames to children with autism.
AB  - The current study extends the mand-for-information literature by examining a
      method to teach mand-for-information frames, targeting 2 frames for the "How?"
      mand ("How do I?" and "How many?"). Using separate behavior chains to target the
      2 frames, we taught 3 children with autism to emit mands for information with 1
      behavior chain and assessed generalization with the remaining behavior chains.
      Behavior chains that the participants were unable to perform independently and
      that produced a desirable outcome for the participant (e.g., tornado water) were
      used to contrive the relevant motivating operation. For all 3 participants, mands
      for information generalized across motivating operations and response
      topographies.

PMID- 24114375
TI  - Micronutrient supplementation for children with HIV infection.
AB  - BACKGROUND: Micronutrient deficiencies are widespread and compound the effects of
      HIV disease in children, especially in poor communities. Micronutrient
      supplements may be effective and safe in reducing the burden of HIV disease. This
      review is an update of an earlier Cochrane review of micronutrient
      supplementation in children and adults which found that vitamin A and zinc are
      beneficial and safe in children exposed to HIV and living with HIV infection
      (Irlam 2010). OBJECTIVES: To assess whether micronutrient supplements are
      effective and safe in reducing mortality and morbidity in children with HIV
      infection. SEARCH METHODS: The CENTRAL, EMBASE, and PubMed databases were
      searched for randomised controlled trials of micronutrient supplements (vitamins,
      trace elements, and combinations of these) using the search methods of the
      Cochrane HIV/AIDS Group. SELECTION CRITERIA: Randomised controlled trials were
      selected that compared the effects of micronutrient supplements with other
      supplements, or placebo or no treatment on the primary outcomes of mortality,
      morbidity, and HIV-related hospitalisations. Indicators of HIV disease
      progession, anthropometric measures, and any adverse effects of supplementation
      were secondary outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently screened and selected trials for inclusion, assessed the risk of
      bias using standardised criteria, and extracted data. Review Manager 5.1 was used
      to calculate the risk ratio (RR) for dichotomous data and the weighted mean
      difference (WMD) for continuous data, and to perform random effects meta-analysis
      where appropriate. MAIN RESULTS: We included three new studies in addition to the
      eight studies in the earlier version of the review (Irlam 2010). Eleven studies
      with a total of 2412 participants were therefore included: five trials of vitamin
      A, one trial of vitamin D, two trials of zinc, and three trials of multiple
      micronutrient supplements. All except one trial were conducted in African
      children.Vitamin A halved all-cause mortality in a meta-analysis of three trials
      in African children, had inconsistent impacts on diarrhoeal and respiratory
      morbidity, and improved short-term growth in a Tanzanian trial. No significant
      adverse effects were reported.A single small trial of vitamin D in North American
      adolescents and children demonstrated safety but no clinical benefits. Zinc
      supplements reduced diarrhoeal morbidity and had no adverse effects on disease
      progression in one small South African trial. Another trial in South African
      children with and without HIV infection did not show benefit from the the
      prophylactic use of zinc or multiple supplements versus vitamin A in the small
      subgroup of children with HIV infection.Multiple micronutrient supplements at
      twice the RDA did not alter mortality, growth, or CD4 counts at 12 months in
      Ugandan children aged one to five years. Short-term supplementation until
      hospital discharge significantly reduced the duration of all hospital admissions
      in poorly nourished South African children, and supplementation for six months
      after discharge improved appetite and nutritional indicators. AUTHORS'
      CONCLUSIONS: Vitamin A supplementation is beneficial and safe in children with
      HIV infection. Zinc is safe and appears to have similar benefits on diarrhoeal
      morbidity in children with HIV as in children without HIV infection. Multiple
      micronutrient supplements have some clinical benefit in poorly nourished children
      with HIV infection.Further trials of single supplements (vitamin D, zinc, and
      selenium) are required to build the evidence base. The long-term effects and
      optimal composition and dosing of multiple micronutrient supplements require
      further investigation in children with diverse HIV disease status.

PMID- 24114376
TI  - Differential expression and regulatory roles of FABP5 and FABP7 in
      oligodendrocyte lineage cells.
AB  - Fatty-acid-binding proteins (FABPs) are key intracellular molecules involved in
      the uptake, transportation and storage of fatty acids and in the mediation of
      signal transduction and gene transcription. However, little is known regarding
      their expression and function in the oligodendrocyte lineage. We evaluate the in
      vivo and in vitro expression of FABP5 and FABP7 in oligodendrocyte lineage cells
      in the cortex and corpus callosum of adult mice, mixed cortical culture and
      oligosphere culture by immunofluorescent counter-staining with major
      oligodendrocyte lineage markers. In all settings, FABP7 expression was detected
      in NG2(+)/PDGFRalpha(+) oligodendrocyte progenitor cells (OPCs) that did not
      express FABP5. FABP5 was detected in mature CC1(+)/MBP(+) oligodendrocytes that
      did not express FABP7. Analysis of cultured OPCs showed a significant decrease in
      the population of FABP7-knockout (KO) OPCs and their BrdU uptake compared with
      wild-type (WT) OPCs. Upon incubation of OPCs in oligodendrocyte differentiation
      medium, a significantly lower percentage of FABP7-KO OPCs differentiated into
      O4(+) oligodendrocytes. The percentage of mature MBP(+) oligodendrocytes relative
      to whole O4(+)/MBP(+) oligodendrocytes was significantly lower in FABP7-KO and
      FABP5-KO than in WT cell populations. The percentage of terminally mature
      oligodendrocytes with membrane sheet morphology was significantly lower in FABP5
      KO compared with WT cell populations. Thus, FABP7 and FABP5 are differentially
      expressed in oligodendrocyte lineage cells and regulate their proliferation
      and/or differentiation. Our findings suggest the involvement of FABP7 and FABP5
      in the pathophysiology of demyelinating disorders, neuropsychiatric disorder and
      glioma, conditions in which OPCs/oligodendrocytes play central roles. 

PMID- 24114377
TI  - Internal deletions of transposable elements: the case of Lemi elements.
AB  - Mobile elements using a "cut and paste" mechanism of transposition (Class II) are
      frequently prone to internal deletions and the question of the origin of these
      copies remains elusive. In this study, we looked for copies belonging to the Lemi
      Family (Tc1-mariner-IS630 SuperFamily) in the plant genomes, and copies within
      internal deletions were analyzed in detail. Lemi elements are found exclusively
      in Eudicots, and more than half of the copies have been deleted. All deletions
      occur between microhomologies (direct repeats from 2 to 13 bp). Copies less than
      500 bp long, similar to MITEs, are frequent. These copies seem to result from
      large deletions occurring between microhomologies present within a region of 300
      bp at both extremities of the element. These regions are particularly A/T rich,
      compared to the internal part of the element, which increases the probability of
      observing short direct repeats. Most of the molecular mechanisms responsible for
      double strand break repair are able to induce deletions between microhomologies
      during the repair process. This could be a quick way to reduce the population of
      active copies within a genome and, more generally, to reduce the overall activity
      of the element after it has entered a naive genome.

PMID- 24114378
TI  - Pericentromeric location of the telomeric DNA sequences on the European grayling
      chromosomes.
AB  - The chromosomal characteristics, locations and variations of the C-band positive
      heterochromatin and telomeric DNA sequences were studied in the European grayling
      karyotype (Thymallus thymallus, Salmonidae) using conventional C-banding,
      endonucleases digestion banding, silver nitrate (AgNO3), chromomycin A3 and 4',6
      diamidino-2-phenylindole staining techniques as well as fluorescence in situ
      hybridization (FISH) and primed in situ labelling. Original data on the
      chromosomal distribution of segments resistant to AluI restriction endonuclease
      and identification of the C-banded heterochromatin presented here have been used
      to characterize the grayling karyotype polymorphism. Structural and length
      polymorphism of the chromosome 21 showing a conspicuous heterochromatin block
      adjacent to the centromere seems to be the result of the deletion and inversion.
      Two pairs of nuclear organizer regions (NOR)-bearing chromosomes were found to be
      polymorphic in size and displaying several distinct forms. FISH with telomeric
      peptide nucleic acid probe enabled recognition of the conservative telomeric DNA
      sequences. The karyotype of the thymallid fish is thought to experienced numerous
      pericentric inversions and internal telomeric sites (ITSs) observed at the
      pericentromeric regions of the six European grayling metacentric chromosomes are
      likely relics of the these rearrangements. None of the ITS sites matched either
      chromosome 21 or NOR bearing chromosomes. 

PMID- 24114379
TI  - Fitting correlated residual error structures in nonlinear mixed-effects models
      using SAS PROC NLMIXED.
AB  - Nonlinear mixed-effects (NLME) models remain popular among practitioners for
      analyzing continuous repeated measures data taken on each of a number of
      individuals when interest centers on characterizing individual-specific change.
      Within this framework, variation and correlation among the repeated measurements
      may be partitioned into interindividual variation and intraindividual variation
      components. The covariance structure of the residuals are, in many applications,
      consigned to be independent with homogeneous variances, [Formula: see text], not
      because it is believed that intraindividual variation adheres to this structure,
      but because many software programs that estimate parameters of such models are
      not well-equipped to handle other, possibly more realistic, patterns. In this
      article, we describe how the programmatic environment within SAS may be utilized
      to model residual structures for serial correlation and variance heterogeneity.
      An empirical example is used to illustrate the capabilities of the module. 

PMID- 24114380
TI  - Learning experience of linear endobronchial ultrasound among pulmonary trainees.
AB  - BACKGROUND: Linear endobronchial ultrasound (EBUS) allows real-time guidance of
      transbronchial needle aspiration of thoracic structures and has become an
      increasingly important diagnostic tool for chest physicians. Little has been
      published about the learning experience of operators with this technology. The
      purpose of this study was to define the learning experience of EBUS-guided
      transbronchial needle aspiration (EBUS-TBNA) among pulmonary trainees. METHODS:
      This was a multicenter cohort study of fellows in pulmonary medicine over the
      first 2 years of their training. Prior to performing EBUS-TBNA, all participants
      had to complete 30 conventional bronchoscopies, an EBUS-specific didactic
      curriculum, and a simulation session with a plastic airway model. Each
      consecutive EBUS procedure was scored with a checklist that evaluated the ability
      to pass a bronchoscope through vocal cords, identify the appropriate node for
      sampling, acquire adequate ultrasound images, guide the bronchoscopy team through
      the technical steps of EBUS-TBNA, and obtain adequate tissue samples. RESULTS:
      Thirteen pulmonary trainees from three training programs were enrolled in the
      study and were observed over a 2-year period. The majority of trainees were able
      to perform all essential steps of EBUS-TBNA and obtain adequate tissue after
      performing an average of 13 (95% CI, 7-16) procedures. CONCLUSIONS: Pulmonary
      trainees needed an average of 13 procedures to achieve first independent
      successful performance of EBUS-TBNA following a training protocol that included a
      didactic curriculum and simulation-based practice. Our findings could guide
      pulmonary fellowship directors in planning EBUS training and establishing a
      reasonable juncture to assess EBUS skills with validated assessment tools.

PMID- 24114381
TI  - [Transcranial cerebral oxymetry in interventional neuroradiology. Sources of
      error in interpretation of measurement data].
AB  - Transcranial cerebral oximetry is a non-invasive method to support the estimation
      of the balance in cerebral oxygen metabolism status during interventional
      neuroradiological procedures. The simple data acquisition can lead to errors by
      oversimplification in interpretation of the displayed data. To avoid fatal
      mistakes of the acquired data the complex interactions of the examined substrate
      with physiological and pathophysiological interactions have to be critically
      judged as well as the procedural approach and methodological limitations. 

PMID- 24114382
TI  - Employment specialist competencies for supported employment programs.
AB  - PURPOSE: Supported employment (SE) programs are evidence-based programs offered
      to people with severe mental illness to facilitate obtaining and keeping
      competitive work. However, significant variations in individuals' vocational
      success may be partly explained by differences in their employment specialists'
      competencies. Aim The main objectives of this study were to develop a
      questionnaire measuring the behaviors, attitudes and knowledge of employment
      specialists working in SE programs and to link specific competencies to
      vocational outcomes. METHODS: A total of 153 employment specialists working in
      Canadian and Dutch supported employment programs completed the Behaviors,
      Attitudes, and Knowledge in Employment Specialists (BAKES) questionnaire and
      provided information about their clients' vocational outcomes. RESULTS:
      Exploratory Factor Analyses results found 90 items over 12 subscales (e.g.,
      Relationships with employers and supervisors). Regression analyses indicated that
      the two most useful subscales for predicting vocational success were: (1)
      Relationships with employers and supervisors, and (2) support and client-centered
      approach. CONCLUSION: Employment specialists require specific competencies to
      help people with severe mental illness obtain and maintain competitive
      employment. Validating the BAKES will better define the broad range of
      competencies expected for this position, and this tool may facilitate training of
      employment specialists.

PMID- 24114383
TI  - Assessment of growth and yield losses in two Zea mays L. cultivars (quality
      protein maize and nonquality protein maize) under projected levels of ozone.
AB  - Rapid industrialization and economic developments have increased the tropospheric
      ozone (O3) budget since preindustrial times, and presently, it is supposed to be
      a major threat to crop productivity. Maize (Zea mays L.), a C4 plant is the third
      most important staple crop at global level with a great deal of economic
      importance. The present study was conducted to evaluate the performance of two
      maize cultivars [HQPM1: quality protein maize (QPM)] and [DHM117: nonquality
      protein maize (NQPM)] to variable O3 doses. Experimental setup included filtered
      chambers, nonfiltered chambers (NFC), and two elevated doses of O3 viz. NFC+15
      ppb O3 (NFC+15) and NFC+30 ppb O3 (NFC+30). During initial growth period, both
      QPM and NQPM plants showed hormetic effect that is beneficial due to exposure of
      low doses of a toxicant (NFC and NFC+15 ppb O3), but at later stages, growth
      attributes were negatively affected by O3. Growth indices showed the variable
      pattern of photosynthate translocation under O3 stress. Foliar injury in the form
      of interveinal chlorosis and reddening of leaves due to increased production of
      anthocyanin pigments was observed at higher concentrations of O3. One-dimensional
      gel electrophoresis of leaves taken from NFC+30 showed reductions of major
      photosynthetic proteins, and differential response was observed between the two
      test cultivars. Decline in the number of male flowers at elevated O3 doses
      suggested damaging effect of O3 on reproductive structures which might be a cause
      of productivity losses. Variable carbon allocation pattern particularly to husk
      leaves, foliar injury, and damage of photosynthetic proteins led to significant
      reductions in economic yield at higher O3 doses. PCA showed that both the
      cultivars responded more or less similarly to O3 stress in their respective
      groupings of growth and yield parameters, but magnitude of their response was
      variable. It is further supported by difference in the significance of
      correlations between variables of yield and AOT40. Cultivar response reflects
      that QPM performed better than NQPM against elevated O3.

PMID- 24114384
TI  - Effects of temperature and amendments on nitrogen mineralization in selected
      Australian soils.
AB  - The effects of temperature (18, 24, and 37  degrees C) and form of nitrogen (N)
      input from various sources (organic-green waste compost, biosolids, and chicken
      manure; inorganic-urea) on N transformation in three different Australian soils
      with varying pH (4.30, 7.09, and 9.15) were examined. Ammonification rate
      (ammonium concentration) increased with increase in temperature in all soil
      types. The effect of temperature on nitrification rate (nitrate concentration)
      followed 24 > 37 > 18  degrees C. Nitrification rate was higher in neutral and
      alkaline soils than acidic soil. Mineral N (bioavailable N) concentration was
      high in urea treatments than in organic N source treatments in all soil types.
      Acidic soil lacked nitrification activity resulting in low nitrate (NO3) buildup
      in urea treatment, whereas a significant NO3 buildup was noticed in green waste
      compost treatment. In neutral and alkaline soils, the nitrification activity was
      low at 37  degrees C in urea treatment but with a significant NO3 buildup in
      organic amendment added soils. Addition of organic N sources supplied ammonia
      oxidizing bacteria thereby triggering nitrification in the soils (even at 37 
      degrees C). This study posits the following implications: (1) inorganic
      fertilizer accumulate high NO3 content in soils in a short period of incubation,
      thereby becoming a potential source of NO3 leaching; (2) organic N sources can
      serve as possible source of nitrifying bacteria, thereby increasing bioavailable
      N (NO3) in soils regardless of the soil properties and temperature.

PMID- 24114385
TI  - Characterization and potential application in mercury bioremediation of highly
      mercury-resistant marine bacterium Bacillus thuringiensis PW-05.
AB  - Bacillus thuringiensis PW-05 was isolated from the Odisha coast and was found to
      resist 50 ppm of Hg as HgCl2 as well as higher concentrations of CdCl2, ZnSO4,
      PbNO3 and Na2HAsO4. Resistance towards several antibiotics, viz amoxycillin,
      ampicillin, methicillin, azithromycin and cephradine (CV) was also observed. The
      mer operon possessed by most of the mercury-resistant bacteria was also found in
      this isolate. Atomic absorption spectroscopy revealed that the isolate can
      volatilize >90 % of inorganic mercury. It showed biofilm formation in the
      presence of 50 ppm HgCl2 and can produce exopolysaccharide under same conditions.
      The isolate was found to volatilize mercury efficiently under a wide range of
      environmental parameters, i.e. pH (7 to 8), temperature (25  degrees C to 40 
      degrees C) and salinity (5 to 25 ppt). merA gene expression has been confirmed by
      real-time reverse transcriptase PCR study. Fourier transform infrared study
      revealed that -SH and -COOH groups play a major role in the process of adaptation
      to Hg. Hence, this isolate B. thuringiensis PW-05 shows an interesting potential
      for bioremediation of mercury.

PMID- 24114386
TI  - Seasonal variation in expression pattern of genes under HSP70 : Seasonal
      variation in expression pattern of genes under HSP70 family in heat- and cold
      adapted goats (Capra hircus).
AB  - Heat shock protein 70 (HSP70) is one of the most abundant and best characterized
      heat shock protein family that consists of highly conserved stress proteins,
      expressed in response to stress, and plays crucial roles in environmental stress
      tolerance and adaptation. The present study was conducted to identify major types
      of genes under the HSP70 family and to quantify their expression pattern in heat-
      and cold-adapted Indian goats (Capra hircus) with respect to different seasons.
      Five HSP70 gene homologues to HSPA8, HSPA6, HSPA1A, HSPA1L, and HSPA2 were
      identified by gene-specific primers. The cDNA sequences showed high similarity to
      other mammals, and proteins have an estimated molecular weight of around 70 kDa.
      The expression of HSP70 genes was observed during summer and winter. During
      summer, the higher expression of HSPA8, HSPA6, and HSPA1A was observed, whereas
      the expression levels of HSPA1L and HSPA2 were found to be lower. It was also
      observed that the expression of HSPA1A and HSPA8 was higher during winter in both
      heat- and cold-adapted goats but downregulates in case of other HSPs. Therefore,
      both heat and cold stress induced the overexpression of HSP70 genes. An
      interesting finding that emerged from the study is the higher expression of HSP70
      genes in cold-adapted goats during summer and in heat-adapted goats during
      winter. Altogether, the results indicate that the expression pattern of HSP70
      genes is species- and breed-specific, most likely due to variations in thermal
      tolerance and adaptation to different climatic conditions.

PMID- 24114387
TI  - Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related
      renal dysfunction induced by TCDD in Wistar rats.
AB  - Humans are systemically exposed to persistent organic pollutants, of which
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental
      concern. Exposure to TCDD results in a wide variety of adverse health effects
      which is mediated by oxidative stress through CYP1A1 activation and arachidonic
      acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and
      competes with arachidonic acid in membrane phospholipids and produces anti
      inflammatory EPA derivatives. Since both EPA and its derivatives have been
      reported to enhance the antioxidant mechanism, the present study aimed at
      studying whether EPA could offer protection against TCDD-induced oxidative stress
      and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and
      creatinine) and histopathological studies revealed that EPA treatment
      significantly reduced TCDD-induced renal damage. TCDD-induced oxidative damage
      was reflected in a significant increase in CYP1A1 activity and lipid peroxide
      levels with a concomitant decline in non-enzymic antioxidant (GSH) and various
      enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione
      S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced
      oxidative stress also resulted in decline in Na(+)-K(+) and Mg(2+)ATPases
      activities with increase in Ca(2+) ATPases activity. Oral treatment with EPA
      showed a significant cytoprotection against TCDD-induced renal oxidative stress
      by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced
      alterations in ATPase enzyme activities were also prevented by EPA treatment. Our
      results show clear evidence that EPA ameliorates TCDD-induced oxidative stress
      and kidney damage; thus suggest the potential of EPA as an effective therapeutic
      agent against toxic effects mediated through redox imbalance.

PMID- 24114389
TI  - Comment: are the measurements of water-filled and air-charged catheters the same
      in urodynamics?

PMID- 24114388
TI  - Dilation and surgical management in vaginal agenesis: a systematic review.
AB  - INTRODUCTION: The management of vaginal agenesis is currently determined by
      geographical location and surgeon preference. The optimal treatment is unknown
      and the majority of articles on technique and outcome focus on personal case
      series with little standardisation of reporting and follow-up. METHODS: Six
      thousand six hundred and ninety-one articles concerning the management of vaginal
      agenesis were systematically reviewed, with 162 fitting the inclusion criteria.
      RESULTS: Only one randomised control trial was included with the remaining
      articles made up of case series or case reports. The bowel vaginoplasty method
      was most commonly reported historically with 945 patients and 45 articles
      included. The Vecchietti procedure had the shortest operative time, but the
      highest number of urological injuries (2.1 %). The split thickness procedure had
      the highest infection rate (4.2 %) and re-operation rate (7.84 %). CONCLUSION:
      Overall, the conservative method using dilation had the fewest complications,
      with an average vaginal length of 6.65 cm (+/- 1.39 cm). However, with an
      operative procedure full consent is imperative, as is an understanding of the
      need for postoperative dilation with the majority of techniques.

PMID- 24114390
TI  - Examining the possible functions of kissing in romantic relationships.
AB  - Recent research suggests that romantic kissing may be utilized in human sexual
      relationships to evaluate aspects of a potential mate's suitability, to mediate
      feelings of attachment between pair-bonded individuals, or to facilitate arousal
      and initiate sexual relations. This study explored these potential functions of
      romantic kissing by examining attitudes towards the importance of kissing in the
      context of various human mating situations. The study involved an international
      online questionnaire, which was completed by 308 male and 594 female participants
      aged 18-63 years. Support was found for the hypothesis that kissing serves a
      useful mate-assessment function: women, high mate-value participants, and
      participants high in sociosexual orientation placed greater importance on kissing
      in romantic relationships and stated that an initial kiss was more likely to
      affect their attraction to a potential mate than did men, low-mate value
      participants or low sociosexual orientation participants. Kissing also seemed to
      be utilized in the mediation of pair-bond attachments: kissing was seen to be
      more important at established stages of relationships by low sociosexual
      participants, kissing was generally seen as more important in long-term
      relationship contexts (but particularly so by women), and kissing frequency was
      found to be related to relationship satisfaction. The findings of this research
      showed very little evidence to support the hypothesis that the primary function
      of kissing is to elevate levels of arousal.

PMID- 24114391
TI  - Can palmar creases serve as landmarks for the deeper neuro-vascular structures?
AB  - PURPOSE: The aim of this study was the examination of the superficial anatomy of
      palmar creases and their relation to deeper neuro-vascular structures. METHODS:
      Four creases: distal wrist flexion crease, thenar crease, proximal palmar crease
      and distal palmar crease were evaluated with reference to the following
      structures: palmar cutaneous branch of median nerve, palmar cutaneous branch of
      ulnar nerve, the nerve of Henle, transverse palmar branches from ulnar nerve,
      recurrent motor branch of median nerve, radial proper palmar digital nerve to the
      index and the ulnar proper palmar digital nerve to the thumb, Berrettini's
      communicating branch, ulnar nerve and artery, superficial palmar arch. We
      performed dissections of 20 cadaveric upper limbs derived from a homogenous
      Caucasian group. In our study we measured the location of surgically important
      structures with reference to palmar skin creases. RESULTS: Among the other
      observations we noticed that the palmar cutaneous branches of the median and
      ulnar nerves were located at least 0.5 cm away from the thenar crease. The
      superficial palmar arch was found between the thenar and proximal palmar crease
      and never crossed the proximal or distal palmar creases. CONCLUSIONS: These
      anatomical dissections will provide reference material for further ultrasound
      studies on the arrangements of neuro-vascular structures in reference to
      superficial palmar creases.

PMID- 24114392
TI  - Dynamic scheduling with due dates and time windows: an application to
      chemotherapy patient appointment booking.
AB  - We study a scheduling problem in which arriving patients require appointments at
      specific future days within a treatment specific time window. This research is
      motivated by a study of chemotherapy scheduling practices at the British Columbia
      Cancer Agency (Canada). We formulate this problem as a Markov Decision Process
      (MDP). Since the resulting MDPs are intractable to exact methods, we employ
      linear-programming-based Approximate Dynamic Programming (ADP) to obtain
      approximate solutions. Using simulation, we compare the performance of the
      resulting ADP policies to practical and easy-to-use heuristic decision rules
      under diverse scenarios. The results indicate that ADP is promising in several
      scenarios, and that a specific easy-to-use heuristic performs well in the
      idealized chemotherapy scheduling setting we study. 

PMID- 24114394
TI  - The number needed to offend: a cross-sectional study of potential offensiveness
      of rheumatic diagnostic labels.
AB  - This study aims to explore the different connotations and potential offensiveness
      of ten mechanistic labels in newly referred Mexican patients with rheumatic
      symptoms as well as in Mexican and Canadian rheumatologists. Patients with
      musculoskeletal complaints newly referred for a rheumatology assessment were
      interviewed consecutively before they saw the rheumatologist. Patients were asked
      to choose one of nine feelings provoked by ten different illness mechanism
      labels. Rheumatologists gave a medical diagnosis after seeing the patients.
      Mexican and Canadian rheumatologists were invited to answer a structured
      questionnaire about their feelings at the moment they identified each of the ten
      different provided scenarios. Patients' and rheumatologists' feelings were
      classified as "offended" or "nonoffended." The "offensive score" was used to
      calculate a "number needed to offend" (NNO). One hundred and fifty patients were
      included. Inherited, immunological, and inflammatory labels had the fewest
      negative connotations (NNOs 17, 12, and 14, respectively), and psychological,
      functional, idiopathic, and sleep disturbance labels had the most (NNO 2 and 3,
      respectively). Functional labels were almost four times more offensive than
      organic labels. Stratified by rheumatologist diagnosis, patients with functional
      disorders were more accepting of organic-based mechanistic labels. A higher
      potential to offend was observed when patients with functional somatic conditions
      were given functional mechanistic labels (NNOs 1 to 4). The survey was completed
      by 186 Mexican rheumatologists and 71 Canadian rheumatologists. Primarily
      functional disorders such as somatization and anxiety had a high potential to
      evoke offensive feelings (NNOs 3 to 7). No significant differences in the NNO
      were found between Mexican and Canadian rheumatologists. Getting or giving
      mechanistic/explanatory labels is emotional. Both patients and rheumatologists
      experienced offended feelings with functional or idiopathic labels. 

PMID- 24114393
TI  - BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated
      production of apurinic/apyrimidinic endonuclease 1.
AB  - Brain-derived neurotrophic factor (BDNF) promotes the survival and growth of
      neurons during brain development and mediates activity-dependent synaptic
      plasticity and associated learning and memory in the adult. BDNF levels are
      reduced in brain regions affected in Alzheimer's, Parkinson's, and Huntington's
      diseases, and elevation of BDNF levels can ameliorate neuronal dysfunction and
      degeneration in experimental models of these diseases. Because neurons accumulate
      oxidative lesions in their DNA during normal activity and in neurodegenerative
      disorders, we determined whether and how BDNF affects the ability of neurons to
      cope with oxidative DNA damage. We found that BDNF protects cerebral cortical
      neurons against oxidative DNA damage-induced death by a mechanism involving
      enhanced DNA repair. BDNF stimulates DNA repair by activating cyclic AMP response
      element-binding protein (CREB), which, in turn, induces the expression of
      apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision
      DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference
      abolishes the ability of BDNF to protect neurons against oxidized DNA damage
      induced death. The ability of BDNF to activate CREB and upregulate APE1
      expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3
      kinase, and Akt kinase. Voluntary running wheel exercise significantly increases
      levels of BDNF, activates CREB, and upregulates APE1 in the cerebral cortex and
      hippocampus of mice, suggesting a novel mechanism whereby exercise may protect
      neurons from oxidative DNA damage. Our findings reveal a previously unknown
      ability of BDNF to enhance DNA repair by inducing the expression of the DNA
      repair enzyme APE1. 

PMID- 24114395
TI  - Learning rates and known-to-unknown flash-card ratios: comparing effectiveness
      while holding instructional time constant.
AB  - Using alternating treatments designs, we compared learning rates across 2
      computer-based flash-card interventions (3 min each): a traditional drill
      intervention with 15 unknown words and an interspersal intervention with 12 known
      words and 3 unknown words. Each student acquired more words under the traditional
      drill intervention. Discussion focuses on the need to account for instructional
      time when learning procedures are evaluated and compared. 

PMID- 24114396
TI  - beta-Adrenergic receptor antagonists and fracture risk: a meta-analysis of
      selectivity, gender, and site-specific effects.
AB  - By meta-analysis, the risk of fracture was 15% lower in patients treated with
      beta-adrenergic blockers compared to controls independent of gender, fracture
      site, and dose. This might be attributable to beta1-selective blockers.
      INTRODUCTION: The aim of this study is to determine by meta-analysis whether beta
      adrenergic blockers (BBs) reduce fracture risk and whether the effect, if
      demonstrable, is dependent upon selectivity, dose, gender, or fracture site.
      METHODS: A literature search was performed in electronic databases MEDLINE,
      EMBASE, and reference sections of relevant articles to identify eligible studies.
      Adjusted estimates of fracture risk effect size (ES) were pooled across studies
      using fixed or random-effects (RE) meta-analysis as appropriate. Dose-related
      effects were evaluated using meta-regression. To explore the relative efficacy of
      beta1-selective blockers in comparison to nonselective BBs, adjusted indirect
      comparison was performed. RESULTS: A total of 16 studies (7 cohort and 9 case
      control studies), involving 1,644,570 subjects, were identified. The risk of any
      fracture was found to be significantly reduced in subjects receiving BBs as
      compared to control subjects (16 studies, RE pooled ES = 0.86, 95% CI 0.78-0.93;
      I(2) = 87 %). In a sensitivity analysis limited to those studies deemed to be
      most robust, the BB effect to reduce fracture risk was sustained (four studies,
      pooled ES = 0.79, 95% CI 0.67-0.94; I(2) = 96%). The risk of a hip fracture was
      lower in both women and men receiving BBs (women: pooled ES = 0.86, 95% CI 0.80
      0.91; I(2) = 1% and men: pooled ES = 0.80, 95% CI 0.71-0.90; I(2) = 0%). Similar
      risk reductions were found for clinical vertebral and forearm fractures, although
      statistical significance was not reached. The reduction in risk did not appear to
      be dose-related (test for a linear trend p value 0.150). Using adjusted indirect
      comparisons, it was estimated that beta1-selective agents were significantly more
      effective than nonselective BBs in reducing the risk of any fracture (six
      studies, beta1-selective blockers vs. nonselective BBs: RE pooled ES = 0.82, 95%
      CI = 0.69-0.97). CONCLUSIONS: The findings suggest that the risk of fracture is
      approximately 15% lower in patients treated with BBs compared to controls
      independent of gender, fracture site, and dose. This risk reduction might be
      associated with the effects of beta1-selective blockers.

PMID- 24114397
TI  - Genistein effects on quality of life and depression symptoms in osteopenic
      postmenopausal women: a 2-year randomized, double-blind, controlled study.
AB  - SUMMARY: Postmenopausal estrogen decline is implicated in several age-related
      physical and psychological changes in women, including decreases in perceived
      quality of life. The phytoestrogen genistein at a dose of 54 mg daily in
      osteopenic postmenopausal women after 2 years implies an improvement on quality
      of life and depression symptoms. INTRODUCTION: Postmenopausal estrogen decline is
      implicated in several age-related physical and psychological changes in women,
      including decreases in perceived quality of life (QoL). A number of trials with
      hormone therapy showed beneficial effects of the intervention on quality of life
      parameters. However, because of known or suspected serious side effects of
      conventional hormone therapy, there is a need for alternatives. METHODS: We
      conducted a double-blind randomized placebo-controlled trial using the isoflavone
      genistein, 54 mg, or placebo for 2 years. In this trial, we recruited 262
      postmenopausal women aged 49 to 67 years. RESULTS: At baseline, after 1 year, and
      at final visit, participants filled in the Short Form of 36 questions (SF-36) and
      the Zung Self-rating Depression Scale (ZSDS). For the placebo group, scores on
      all dimensions of the SF-36 decreased after 1 and 2 years. The genistein group
      showed increases on all dimensions of the SF-36 at the end of the study. There
      were, however, statistically significant differences in changes of scores between
      the two intervention groups. For the ZSDS, similarly, significant differences
      were found between groups. CONCLUSION: In conclusion, the findings of this
      randomized trial showed that genistein improves quality of life (health status,
      life satisfaction, and depression) in osteopenic postmenopausal women.

PMID- 24114398
TI  - Comparative cost-effectiveness of bazedoxifene and raloxifene in the treatment of
      postmenopausal osteoporosis in Europe, using the FRAX algorithm.
AB  - Bazedoxifene and raloxifene were evaluated in the treatment of postmenopausal
      osteoporosis from health economic perspective in Europe. Based on a computer
      based algorithm calculating efficacy of the treatments, bazedoxifene appears to
      be a cost-effective strategy compared to raloxifene, particularly in patients at
      high fracture risk. INTRODUCTION: The purpose of this study was to compare cost
      effectiveness of bazedoxifene and raloxifene in eight European countries:
      Belgium, France, Germany, Ireland, Italy, Spain, Sweden, and the UK. METHODS: The
      Fracture Risk Assessment Tool, which is a computer-based algorithm to calculate
      fracture probability using clinical risk factors alone or with bone mineral
      density, was incorporated in a Markov Tunnel model to evaluate cost-effectiveness
      of bazedoxifene 20 or 40 mg vs. raloxifene 60 mg in postmenopausal osteoporotic
      women. The efficacy of bazedoxifene and raloxifene for vertebral and non
      vertebral fractures was measured as a function of the 10-year probability of a
      major osteoporotic fracture. The model estimated the incremental cost
      effectiveness ratio and net monetary benefit (NMB) from a healthcare perspective,
      given the willingness to pay <euro>30,000. RESULTS: In postmenopausal
      osteoporotic women, bazedoxifene was a cost saving strategy compared to
      raloxifene in the countries studied. The median NMB of bazedoxifene compared to
      raloxifene increased monotonically with the 10-year fracture probability. In
      general, the median NMB became greater than 0 in women with 10-year probabilities
      of a major osteoporotic fracture between 5 and 10% or above. The impact on
      results by varying the assumptions in the model was examined in sensitivity
      analysis. CONCLUSION: Bazedoxifene appears to be a cost-effective strategy
      compared to raloxifene for the treatment of postmenopausal osteoporotic women in
      Europe, particularly in patients at high fracture risk.

PMID- 24114399
TI  - The clinical utility of FRAX to discriminate fracture status in men and women
      with chronic kidney disease.
AB  - We assessed the ability of the World Health Organization's fracture risk
      assessment tool (FRAX), bone mineral density (BMD), and age to discriminate
      fracture status in adults with pre-dialysis chronic kidney disease (CKD). In
      adults with CKD, FRAX was able to discriminate fracture status but performed no
      better than BMD alone. INTRODUCTION: Patients with CKD are at increased risk for
      fracture but the best method to assess fracture risk is not known. METHODS: We
      assessed the ability of the World Health Organization's FRAX, compared with BMD
      at the femoral neck (FN), and age to discriminate fracture status (prevalent
      clinical nonspine and/or morphometric vertebral) in men and women, 18 years and
      older with pre-dialysis CKD. Results are presented as area under receiver
      operator characteristic curves (AUC) with 95% confidence intervals (CI). RESULTS:
      We enrolled 353 subjects; mean age was 65 +/- 14 years; weight was 79 +/- 18 kg,
      and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third
      of the subjects had a prevalent clinical nonspine and/or morphometric vertebral
      fracture. FRAX was able to discriminate among those with prevalent clinical
      nonspine fractures (AUC, 0.72; 95% CI, 0.65-0.78), morphometric vertebral
      fractures (AUC, 0.66; 95% CI, 0.59-0.73), and any fracture (AUC, 0.71; 95% CI,
      0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX
      for morphometric vertebral and any fractures; FRAX performed better than BMD for
      prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95% CI, 0.60
      0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types.
      CONCLUSIONS: Among men and women with CKD, FRAX is able to discriminate fracture
      status but performs no better than BMD alone.

PMID- 24114400
TI  - The Auckland calcium study: 5-year post-trial follow-up.
AB  - Five years after completion of a randomised placebo-controlled trial of calcium
      supplements, there was no effect of calcium on total fracture incidence, a
      significant reduction in vertebral and forearm fractures and, in a subset, no
      effect on bone density. There was no increased risk of cardiovascular events
      after discontinuation of calcium. INTRODUCTION: The Auckland calcium study was a
      5-year randomised controlled trial of 1 g/day calcium citrate in 1,471
      postmenopausal women. Calcium did not reduce total, vertebral or forearm fracture
      incidence, increased hip fracture incidence and had beneficial effects on bone
      mineral density (BMD). A secondary analysis raised concerns about the
      cardiovascular safety of calcium. The purpose of this study was to determine
      whether the effects of calcium on fracture incidence, BMD and cardiovascular
      endpoints persisted after supplement discontinuation. METHODS: Approximately 5
      years post-trial, we collected information on the 1,408 participants alive at
      trial completion from the national databases of hospital admissions and deaths.
      We contacted 1,174 women by phone, and from these we obtained information on
      medical events and post-trial calcium use. We undertook BMD measurements at 10
      years in a selected subset of 194 women who took study medication for 5 years in
      the original trial, and did not take bone-active medications post-trial. RESULTS:
      Over the 10-year period, there was no effect on total fracture (HR 0.90, 95% CI
      0.75-1.07) or hip fracture incidence (1.40, 0.89-2.21), but significant
      reductions in forearm (0.62, 0.43-0.89) and vertebral fractures (0.52, 0.32-0.85)
      in those assigned to calcium. There were no between-group differences in BMD at
      10 years at any site. The adverse cardiovascular outcomes observed in the 5-year
      trial did not persist post-trial. CONCLUSION: Calcium supplementation for 5 years
      had no effect on total fracture incidence at 10 years. The positive benefits on
      BMD and the adverse cardiovascular effects did not persist once supplements were
      stopped.

PMID- 24114401
TI  - Isolation and characterization of human osteoblasts from needle biopsies without
      in vitro culture.
AB  - SUMMARY: We isolate and characterize osteoblasts from humans without in vitro
      culture. These techniques should be broadly applicable to studying the
      pathogenesis of osteoporosis and other bone disorders. INTRODUCTION: There is
      currently no data regarding the expression of specific genes or pathways in human
      osteoblasts that have not been subjected to extensive in vitro culture. Thus, we
      developed methods to rapidly isolate progressively enriched osteoblast
      populations from humans and characterized these cells. METHODS: Needle bone
      biopsies of the posterior iliac crest were subjected to sequential collagenase
      digests. The cells from the second digest were stained with an alkaline
      phosphatase (AP) antibody, and the AP+ cells were isolated using magnetic cell
      sorting. RESULTS: Relative to AP- cells, the AP+ cells contained virtually all of
      the mineralizing cells and were enriched for key osteoblast marker genes. The AP+
      cells were further purified by depletion of cells expressing CD45, CD34, or CD31
      (AP+/CD45/34/31- cells), which represented a highly enriched human osteoblast
      population devoid of hematopoietic/endothelial cells. These cells expressed
      osteoblast marker genes but very low to undetectable levels of SOST. We next used
      high-throughput RNA sequencing to compare the transcriptome of the AP+/CD45/34/31
      cells to human fibroblasts and identified genes and pathways expressed only in
      human osteoblasts in vivo, but not in fibroblasts, including 448 genes unique to
      human osteoblasts. CONCLUSIONS: We provide a detailed characterization of highly
      enriched human osteoblast populations without in vitro culture. These techniques
      should be broadly applicable to studying the pathogenesis of osteoporosis and
      other bone disorders.

PMID- 24114402
TI  - A school-based resistance intervention improves skeletal growth in adolescent
      females.
AB  - SUMMARY: Twenty-two sixth-grade girls who participated in a 7-month school-based
      resistance-training program were compared to 22 controls. In a subanalysis of
      Tanner breast II (T2) and III (T3) subjects (n = 21 controls subjects (CON), n =
      17 subjects in the high-intervention (INT)-dose group (HI)), T2 HI had greater
      narrow neck (NN) width gains than T2 CON (p < 0.05) and T3 HI had greater L3 bone
      mineral density (BMD) gains than T3 CON (p < 0.05). INTRODUCTION: Physical
      activity modulates bone growth during adolescence, but an effective activity has
      not been identified for general use. The purpose of this study was to examine the
      effect of a school-based resistance-training program on skeletal growth in pre
      menarcheal females. METHODS: Sixth-grade girls participated in a 7-month,
      resistance-training program (INT) embedded in physical education (PE) classes.
      Age- and maturity-matched CON from a neighboring school participated in the
      standard PE classes. INT dose defined high (HI) and low (LO) groups. At baseline
      (BL) and follow-up (FU), non-INT organized physical activity (PA, hours per week)
      and maturity status were recorded; DXA scans assessed total body, distal radius,
      proximal femur, and lumbar spine. Regression models analyzed growth in bone
      outcomes for HI versus CON, accounting for age, Tanner stage, height, and PA.
      RESULTS: Forty-four girls (22 HI, 22 CON) were 11.7 +/- 0.3 years of age at BL;
      all were <=6 months postmenarche and did not differ in bone growth over the
      course of the intervention (p > 0.05). However, in a subanalysis limited to
      subjects who were T2 or T3 at BL (n = 21 CON, n = 17 HI), T2 HI had greater gains
      in NN width (p = 0.01) compared to T2 CON, while T3 HI had greater gains in L3
      BMD (p = 0.03) compared to T3 CON. CONCLUSIONS: In a group of T2 and T3 sixth
      grade girls, a school-based resistance-training intervention produced maturity
      specific differential gains for HI versus CON at the hip and spine.

PMID- 24114403
TI  - Bird community responses to the edge between suburbs and reserves.
AB  - New insights into community-level responses at the urban fringe, and the
      mechanisms underlying them, are needed. In our study, we investigated the
      compositional distinctiveness and variability of a breeding bird community at
      both sides of established edges between suburban residential areas and woodland
      reserves in Canberra, Australia. Our goals were to determine if: (1) community
      level responses were direct (differed with distance from the edge, independent of
      vegetation) or indirect (differed in response to edge-related changes in
      vegetation), and (2) if guild-level responses provided the mechanism underpinning
      community-level responses. We found that suburbs and reserves supported
      significantly distinct bird communities. The suburban bird community,
      characterised by urban-adapted native and exotic species, had a weak direct edge
      response, with decreasing compositional variability with distance from the edge.
      In comparison, the reserve bird community, characterised by woodland-dependent
      species, was related to local tree and shrub cover. This was not an indirect
      response, however, as tree and shrub cover was not related to edge distance. We
      found that the relative richness of nesting, foraging and body size guilds also
      displayed similar edge responses, indicating that they underpinned the observed
      community-level responses. Our study illustrates how community-level responses
      provide valuable insights into how communities respond to differences in
      resources between two contrasting habitats. Further, the effects of the suburban
      matrix penetrate into reserves for greater distances than previously thought.
      Suburbs and adjacent reserves, however, provided important habitat resources for
      many native species and the conservation of these areas should not be discounted
      from continued management strategies. 

PMID- 24114404
TI  - Sleep apnea syndrome and hypothyroidism.

PMID- 24114405
TI  - Clinical implication of elevated CA 19-9 level and the relationship with glucose
      control state in patients with type 2 diabetes.
AB  - The aim is to investigate whether there is a difference in CA 19-9 levels between
      diabetes and healthy subjects except malignancies and associated factors with CA
      19-9 in diabetes. We performed a retrospective analysis in 146 type 2 diabetes
      and 154 healthy subjects who visited our medical institution from 2005 to 2009.
      We compared the CA 19-9 in each group, and analyzed clinical and biochemical
      variables in diabetes. The average value of CA 19-9 in diabetes was higher than
      that of healthy subjects significantly (14.1 vs 8.1 U/mL, p < 0.01). CA 19-9 had
      a positive correlation with HbA1c (r = 0.22), fasting plasma glucose (r = 0.24),
      and C-reactive protein (r = 0.38) in diabetes (p < 0.05). 48 type 2 diabetes who
      showed decreased CA 19-9 during follow-up of 1.8 +/- 1.0 years were also improved
      in glucose control state. The proportion of insulin use for glucose control was
      significantly higher in the group of CA 19-9 >= 37 U/mL (75.0 %) as compared with
      the group of CA 19-9 < 37 U/mL (34.0 %). CA 19-9 was significantly higher in the
      patients with diabetic peripheral neuropathy (DPN) as compared with those without
      DPN (p = 0.02). However, after excluding the influences from glycemic control
      state, significant difference was not observed. Our results indicate not only
      that CA 19-9 is influenced by glycemic control state but also can be elevated
      irrespective of any malignancy in diabetes. Therefore, CA 19-9 should be
      interpreted carefully in diabetic patients when CA 19-9 is used as the tool for
      malignancy screening.

PMID- 24114407
TI  - Serum ischaemic-modified albumin levels might not be a marker of oxidative stress
      in patients with hypothyroidism.

PMID- 24114406
TI  - Knockdown of prolactin receptors in a pancreatic beta cell line: effects on DNA
      synthesis, apoptosis, and gene expression.
AB  - Prolactin (PRL) and placental lactogen stimulate beta cell replication and
      insulin production in vitro and in vivo. The molecular mechanisms by which
      lactogens promote beta cell expansion are unclear. We treated rat insulinoma
      cells with a PRL receptor (PRLR) siRNA to determine if PRLR signaling is required
      for beta cell DNA synthesis and cell survival and to identify beta cell cycle
      genes whose expression depends upon lactogen action. Effects of PRLR knockdown
      were compared with those of PRL treatment. PRLR knockdown (-80 %) reduced DNA
      synthesis, increased apoptosis, and inhibited expression of cyclins D2 and B2,
      IRS-2, Tph1, and the anti-apoptotic protein PTTG1; p21 and BCL6 mRNAs increased.
      Conversely, PRL treatment increased DNA synthesis, reduced apoptosis, and
      enhanced expression of A, B and D2 cyclins, CDK1, IRS-2, FoxM1, BCLxL, and PTTG1;
      BCL6 declined. PRLR signaling is required for DNA synthesis and survival of rat
      insulinoma cells. The effects of lactogens are mediated by down-regulation of
      cell cycle inhibitors (BCL6, p21) and induction of A, B, and D2 cyclins, IRS-2,
      Tph1, FoxM1, and the anti-apoptotic proteins BCLxL and PTTG1.

PMID- 24114408
TI  - County workforce, reimbursement, and organizational factors associated with
      behavioral health capacity in health centers.
AB  - This study describes on-site behavioral health treatment capacity in health
      centers in 2007 and examines whether capacity was associated with health center
      characteristics, county-level behavioral health workforce, and same-day billing
      restrictions. Cross-sectional data from the 2007 Area Resource File and Uniform
      Data System were linked with data on Medicaid same-day billing restrictions.
      Mental health treatment capacity was common; almost four in five health centers
      provided on-site mental health services. Additional services such as crisis
      counseling (20 %), treatment from a psychiatrist (29 %), and substance abuse
      treatment were offered by fewer health centers (51 % provide on-site services and
      only 20 % employ substance abuse specialists). In multivariate analysis, larger
      health centers, health centers located in counties with a larger behavioral
      health workforce per capita, and those located in the West and Northeast were
      more likely to have behavioral health capacity. Same-day billing restrictions
      were associated with lower odds of substance use treatment capacity and providing
      24 hr crisis counseling services. 

PMID- 24114409
TI  - Health promotion behaviors in adolescents: prevalence and association with mental
      health status in a statewide sample.
AB  - The purpose of this study is to estimate the proportion of adolescents meeting
      Healthy People 2020 health behavior recommendations for the prevention of chronic
      disease and to determine the association between mental health status (depression
      and/or conduct problems) and the likelihood of meeting these recommendations. The
      data used for this study are from the 2010 Washington State Healthy Youth Survey.
      Descriptive statistics and linear regression were utilized to estimate the
      proportion of adolescents meeting recommendations and associations between youth
      mental health status indicators and health-promoting behaviors. A small minority
      (5.8 %) of youth met all six recommendations in domains of tobacco abstinence,
      substance use abstinence, daily physical activity, breakfast consumption, weight
      below obese levels, and adequate sleep, though most (84.3 %) met at least three.
      At the aggregate level, the proportion of Washington State youth who met Healthy
      People 2020 guidelines exceeded targets, with the exception of substance use
      abstinence. A minority of youth reported guideline levels of daily physical
      activity (23.3 %) and sleep (39.8 %). Mental health status was strongly
      associated with the number of health-promoting behaviors adolescents endorsed.
      Interventions to increase the adoption of sleep hygiene and exercise habits
      should be added to an integrative positive youth development framework within
      school-, community-, and primary care-based adolescent health initiatives.
      Attention to adolescent mental health and shared risk factors may be critical for
      reducing barriers to healthy behavior. 

PMID- 24114410
TI  - Differences in end-of-life care in the ICU across patients cared for by medicine,
      surgery, neurology, and neurosurgery physicians.
AB  - BACKGROUND: Some of the challenges in the delivery of high-quality end-of-life
      care in the ICU include the variability in the characteristics of patients with
      certain illnesses and the practice of critical care by different specialties.
      METHODS: We examined whether ICU attending specialty was associated with quality
      of end-of-life care by using data from a clustered randomized trial of 14
      hospitals. Patients died in the ICU or within 30 h of transfer and were
      categorized by specialty of the attending physician at time of death (medicine,
      surgery, neurology, or neurosurgery). Outcomes included family ratings of
      satisfaction, family and nurse ratings of quality of dying, and documentation of
      palliative care in medical records. Associations were tested using multipredictor
      regression models adjusted for hospital site and for patient, family, or nurse
      characteristics. RESULTS: Of 3,124 patients, the majority were cared for by an
      attending physician specializing in medicine (78%), with fewer from surgery
      (12%), neurology (3%), and neurosurgery (6%). Family satisfaction did not vary by
      attending specialty. Patients with neurology or neurosurgery attending physicians
      had higher family and nurse ratings of quality of dying than patients of
      attending physicians specializing in medicine (P < .05). Patients with surgery
      attending physicians had lower nurse ratings of quality of dying than patients
      with medicine attending physicians (P < .05). Chart documentation of indicators
      of palliative care differed by attending specialty. CONCLUSIONS: Patients cared
      for by neurology and neurosurgery attending physicians have higher family and
      nurse ratings of quality of dying than patients cared for by medicine attending
      physicians and have a different pattern of indicators of palliative care.
      Patients with surgery attending physicians had fewer documented indicators of
      palliative care. These findings may provide insights into potential ways to
      improve the quality of dying for all patients. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00685893; URL: www.clinicaltrials.gov.

PMID- 24114412
TI  - Technical note: geometric morphometrics and sexual dimorphism of the greater
      sciatic notch in adults from two skeletal collections: the accuracy and
      reliability of sex classification.
AB  - The greater sciatic notch (GSN) is one of the most important and frequently used
      characteristics for determining the sex of skeletons, but objective assessment of
      this characteristic is not without its difficulties. We tested the robustness of
      GSN sex classification on the basis of geometric morphometrics (GM) and support
      vector machines (SVM), using two different population samples. Using photographs,
      the shape of the GSN in 229 samples from two assemblages (documented collections
      of a Euroamerican population from the Maxwell Museum, University of New Mexico,
      and a Hispanic population from Universidad Nacional Autonoma de Mexico, Mexico
      City) was segmented automatically and evaluated using six curve representations.
      The optimal dimensionality for each representation was determined by finding the
      best sex classification. The classification accuracy of the six curve
      representations in our study was similar but the highest and concurrently
      homologous cross-validated accuracy of 92% was achieved for a pooled sample using
      Fourier coefficient and Legendre polynomial methods. The success rate of our
      classification was influenced by the number of semilandmarks or coefficients and
      was only slightly affected by GSN marginal point positions. The intrapopulation
      variability of the female GSN shape was significantly lower compared with the
      male variability, possibly as a consequence of the intense selection pressure
      associated with reproduction. Males were misclassified more often than females.
      Our results show that by using a suitable GSN curve representation, a GM
      approach, and SVM analysis, it is possible to obtain a robust separation between
      the sexes that is stable for a multipopulation sample.

PMID- 24114411
TI  - Cis-suppression to arrest protein aggregation in mammalian cells.
AB  - Protein misfolding and aggregation are implicated in numerous human diseases and
      significantly lower production yield of proteins expressed in mammalian cells.
      Despite the importance of understanding and suppressing protein aggregation in
      mammalian cells, a protein design and selection strategy to modulate protein
      misfolding/aggregation in mammalian cells has not yet been reported. In this
      work, we address the particular challenge presented by mutation-induced protein
      aggregation in mammalian cells. We hypothesize that an additional mutation(s) can
      be introduced in an aggregation-prone protein variant, spatially near the
      original mutation, to suppress misfolding and aggregation (cis-suppression). As a
      model protein, we chose human copper, zinc superoxide dismutase mutant (SOD1(A4V)
      ) containing an alanine to valine mutation at residue 4, associated with the
      familial form of amyotrophic lateral sclerosis. We used the program RosettaDesign
      to identify Phe20 in SOD1(A4V) as a key residue responsible for SOD1(A4V)
      conformational destabilization. This information was used to rationally develop a
      pool of candidate mutations at the Phe20 site. After two rounds of mammalian-cell
      based screening of the variants, three novel SOD1(A4V) variants with a
      significantly reduced aggregation propensity inside cells were selected. The
      enhanced stability and reduced aggregation propensity of the three novel
      SOD1(A4V) variants were verified using cell fractionation and in vitro stability
      assays.

PMID- 24114413
TI  - Quantification of bacterial uropathogens in preclinical samples using real-time
      PCR assays.
AB  - Uropathogenic Escherichia coli (UPEC) and Staphylococcus saprophyticus (S.
      saprophyticus) are responsible for the majority of community-acquired urinary
      tract infections (UTI). Agar plating, a gold standard for detection of bacterial
      uropathogens, is labor intensive, limited for distinguishing between
      environmental contaminants and pathogens, and fails to effectively detect mixed
      infections. A reliable method for specific and sensitive quantitative assessment
      of infections would allow cost-effective evaluation of large numbers of
      experimental samples. A methodology such as quantitative PCR (qPCR) addresses the
      limitations of agar plating. We developed and validated highly specific and
      sensitive qPCR assays to assist researchers in the evaluation of potential
      vaccines and interventions in preclinical models of UPEC and S. saprophyticus
      UTI. The developed UPEC PCR targeted a highly conserved region of the UPEC
      hemolysin D (hlyD) gene that reproducibly detected type strains CFT073 and J96
      over a 9 log range with high precision. To quantify S. saprophyticus genomes, a
      separate qPCR assay targeting the Trk transport gene was developed with an 8 log
      range. Neither assay detected bacterial species predicted to be sample
      contaminants. Using our optimized workflow that includes automated steps, up to
      200 urine or tissue samples can be processed in as few as 3 h. Additionally,
      sequence comparisons of our primers and probe to other UTI bacterial strains
      indicated the broad applicability of these assays. These optimized qPCR assays
      provide a cost-effective and time-saving method for quantification of bacterial
      burdens in tissues and body fluids to assess the effectiveness of candidate
      vaccines or interventions. 

PMID- 24114414
TI  - Sensitivity to antibiotics of Clostridium difficile toxigenic nosocomial strains.
AB  - Clostridium difficile is the etiological agent of diarrhoea and colitis,
      especially in elderly patients. The incidence of these diseases has increased
      during the last 10 years. Emergence of so-called hypervirulent strains is
      considered as one of the main factors responsible for the more severe disease and
      changed profile of sensitivity to antimicrobial agents. The aim of this work was
      to determine the sensitivity profile of toxigenic strains of C. difficile in the
      Czech Republic in 2011-2012 to selected antibiotics. The antibiotics clindamycin,
      metronidazole, vancomycin and amoxicillin with clavulanic acid were used for this
      purpose. Isolates cultured on Brazier's C. difficile selective agar were analysed
      for the presence of toxin genes using Xpert detection system. Xpert analysis
      revealed that 33 strains carried the genes for toxins tcdB, cdt and tcdCDelta117,
      thus showing characteristics typical for the hypervirulent ribotype 027/PFGE type
      NAP1/REA type B1. The remaining 29 strains carried only the gene for toxin B
      (tcdB) and not cdt and tcdCDelta117. Our results indicate the higher
      susceptibility of C. difficile hypertoxigenic strains to three out of four tested
      antibiotics (except vancomycin) than it is for the other toxigenic strains. We
      found that only 10.34% of other toxigenic strains were resistant to clindamycin,
      and no resistance was found in all other cases. All the isolates were sensitive
      to amoxicillin/clavulanic acid in vitro. However, its use is not recommended for
      therapy of infections caused by C. difficile.

PMID- 24114415
TI  - Feedback modeling of non-esterified fatty acids in obese Zucker rats after
      nicotinic acid infusions.
AB  - This study investigates the impact of disease on nicotinic acid (NiAc)-induced
      changes in plasma concentrations of non-esterified fatty acids (NEFA). NiAc was
      given by constant intravenous infusion to normal Sprague-Dawley and obese Zucker
      rats, and arterial blood samples were taken for analysis of NiAc, NEFA, insulin
      and glucose plasma concentrations. The intravenous route was intentionally
      selected to avoid confounding processes, such as absorption, following
      extravascular administration. Data were analyzed using nonlinear mixed effects
      modeling (NONMEM, version VI). The disposition of NiAc in the normal rats was
      described by a two-compartment model with endogenous synthesis of NiAc and two
      parallel capacity-limited elimination processes. In the obese rats disposition
      was described by a one-compartment model with endogenous synthesis of NiAc and
      one capacity-limited elimination process. The plasma concentration of NiAc drove
      NEFA (R) turnover via an inhibitory drug-mechanism function acting on the
      formation of NEFA. NEFA turnover was described by a feedback model with a
      moderator distributed over a series of transit compartments, where the first
      compartment (M 1 ) inhibited the formation of R and the last compartment (M N )
      stimulated the loss of R. All processes regulating plasma NEFA concentrations
      were assumed to be captured by the moderator function. Differences in the
      pharmacodynamic response of the two strains included, in the obese animals, an
      increased NEFA baseline, diminished rebound and post-rebound oscillation, and a
      more pronounced slowly developing tolerance during the period of constant drug
      exposure. The feedback model captured the NiAc-induced changes in NEFA response
      in both the normal and obese rats. Differences in the parameter estimates between
      the obese and normal rats included, in the former group, increases in R 0 , k in
      and p by 44, 41 and 78 %, respectively, and decreases in k out and gamma by 64
      and 84 %, respectively. The estimates of k tol and IC 50 were similar in both
      groups. The NiAc-NEFA concentration-response relationship at equilibrium was
      substantially different in the two groups, being shifted upwards and to the
      right, and being shallower in the obese rats. The extent of such shifts is
      important, as they demonstrate the impact of disease at equilibrium and, if
      ignored, will lead to erroneous dose predictions and, in consequence, poorly
      designed studies. The proposed models are primarily aimed at screening and
      selecting candidates with the highest potential of becoming a viable drug in man.

PMID- 24114416
TI  - Introduction: children and consent to treatment.

PMID- 24114417
TI  - [In Process Citation].

PMID- 24114418
TI  - [Acute appendicitis mimicking cholecystitis. Case reports and review with focus
      on medicolegal aspects].
AB  - Since 1955 simultaneous presentation of acute appendicitis und acute
      cholecystitis have been described. These cases are understood as concomitance on
      the one hand and as imitation or induction of acute cholecystitis due to acute
      appendicitis. In laparoscopic surgery for inflammatory diseases, in particular
      acute cholecystitis, exploration of the entire abdomen should be more than
      cursory. In remarkable postoperative courses after cholecystectomy in acute
      cholecystitis, acute appendicitis should be taken into account if it could not be
      excluded intraoperatively. 

PMID- 24114419
TI  - [Prevalence of metastasis in T1 squamous cell carcinoma of the esophagus: a
      retrospective analysis of 295 patients].

PMID- 24114420
TI  - [Early laparoscopic cholecystectomy as therapy of choice for acute
      cholecystitis].

PMID- 24114421
TI  - Intense pulsed light versus benzoyl peroxide 5% gel in treatment of acne
      vulgaris.
AB  - Acne is a common disorder affecting the pilosebaceous unit. Despite many advances
      in the treatments of acne vulgaris the best option is still controversial as the
      pathogenesis of acne is rather complex, necessitating various combination
      therapies. The objective of this study is to compare the clinical efficacy of
      intense pulsed light therapy (IPL) versus benzoyl peroxide 5% for the treatment
      of inflammatory acne. Fifty patients of both sexes, (15 males and 35 females)
      aged (18-27 years), with mild-to-severe acne and Fitzpatrick skin phototype IV
      were enrolled in this study. The patients were equally divided into two groups.
      The first group was treated by benzoyl peroxide while the second group was
      treated by IPL. For both therapies, patients experienced a significant reduction
      in the mean of the inflammatory lesion counts over the treatment period.
      Comparing the effects of both therapies, BP produced better results than IPL. The
      difference in the results was statistically significant at the midpoint of the
      study. However, this difference was insignificant at the end of study. Treatment
      with both benzoyl peroxide and IPL resulted in considerable improvement of the
      acne after 5 weeks of treatment. Comparing the effects of both therapies, BP
      produced better results than IPL. The difference in the results was statistically
      significant at the midpoint of the study. However, this difference was
      insignificant at the end of study.

PMID- 24114423
TI  - Effects of dictation-taking and match-to-sample training on listing and spelling
      responses in adults with intellectual disabilities.
AB  - Several studies have demonstrated that conditions can be arranged to promote
      increases in a nontargeted verbal operant following instruction of another verbal
      operant. In the current study, we used a multiple baseline design to evaluate the
      effects of 2 instructional protocols on nontargeted verbal repertoires (listing
      of synonyms and vocal spelling of these synonyms) in adults with intellectual
      disabilities. In Experiment 1, participants were instructed in taking dictation
      and were tested for the vocal spelling of the words taught during instruction. In
      Experiment 2, participants were taught to match printed words to their printed
      synonyms and tested for the vocal spelling and listing of synonyms. In both
      experiments, interventions promoted increases in nontargeted verbal skills. 

PMID- 24114422
TI  - Carboplatin synergistically triggers the efficacy of photodynamic therapy via
      caspase 3-, 8-, and 12-dependent pathways in human anaplastic thyroid cancer
      cells.
AB  - Anaplastic thyroid cancer is one of the most aggressive forms of malignancies
      which grow very rapidly. Several conventional methods have been applied for the
      treatment of anaplastic thyroid cancer, but most of them were not successful in
      complete recovery of the patients. Therefore, a combination of two or more
      conventional modalities is being applied nowadays for the treatment of this type
      of cancer. In this present study, the combination of photodynamic therapy (PDT)
      and chemotherapy has been studied in anaplastic thyroid cancer. Human anaplastic
      thyroid cancer cells FRO were treated with a chemotherapy drug, carboplatin (cis
      diammine-1,1-cyclobutanedicarboxyl-ateplatinum II (CBDCA)), and radachlorin
      mediated PDT individually and in combination. Several parameters like
      cytotoxicity assay by MTT, apoptosis study by annexin V and propidium iodide,
      cell cycle analysis by flow cytometry, confocal microscopic study, and Western
      blot analysis for different apoptosis-related proteins like Bax, cytochrome c,
      caspases 3, 9, 8, and 12, etc. were studied to check the efficacy of the
      combination treatment as well as to find out the mechanism of this enhanced
      efficacy. Results showed that both PDT and CBDCA can induce apoptosis in FRO
      cells. However, a synergistic efficacy was observed when the cells were treated
      with CBDCA and PDT in combination. Changes in mitochondrial membrane potential
      and an increase in reactive oxygen species generation were observed in
      combination treatments. The enhanced expression of different apoptotic pathway
      related proteins like Bax, cytochrome c, caspase 3, caspase 8, caspase 12, etc.
      also confirmed the higher efficacy of combination treatment. Therefore, with this
      combination treatment, not only a higher efficacy can be achieved but also the
      effective dose of the chemotherapy drug can be reduced, and hence, the adverse
      side effects of the chemotherapy drugs can also be controlled. 

PMID- 24114424
TI  - Sex offenders and sex crime recidivism: investigating the role of sentence length
      and time served.
AB  - The relationship between criminal justice sanctions and sex crime recidivism
      remains largely unexplored. Therefore, using a sample of 8,461 previously
      incarcerated male sex offenders from 13 states in the United States, we focus on
      the sentence meted out for the sex crime conviction and the amount of time sex
      offenders served as a result of their conviction. Sex offenders were grouped into
      four categories: rapists, sexual assaulters, child molesters, and all sex
      offenders combined. Recidivism was operationalized as rearrest and reconviction.
      Findings suggest how recidivism is operationalized matters. When recidivism is
      measured as rearrest for another sex offense, sentence length and time served are
      unrelated to sex crime recidivism. On the other hand, when recidivism is
      operationalized as reconviction for another sex offense, sentence length is
      positively related to recidivism for rapists, sexual assaulters, child molesters,
      and all sex offenders combined, while time served is negatively related to
      recidivism for child molesters and all sex offenders combined. 

PMID- 24114425
TI  - Acute effects of mecamylamine and varenicline on cognitive performance in non
      smokers with and without schizophrenia.
AB  - RATIONALE: Nicotinic acetylcholine receptors (nAChRs) have been implicated in the
      pathophysiology of cognitive deficits in the domains of attention and memory in
      schizophrenia. While nicotinic agonists and antagonists have been proposed as
      smoking cessation aids, few comparisons have been made of these agents on
      cognitive performance in individuals with schizophrenia. OBJECTIVES: This study
      investigated the acute effects of a nAChR antagonist, mecamylamine, and partial
      agonist, varenicline, on cognitive function in non-smokers with and without
      schizophrenia. METHODS: Single oral doses of mecamylamine 10 mg, varenicline 1
      mg, and placebo were administered 1 week apart in random order to adults with
      schizophrenia (n = 30) and to healthy volunteers (n = 41) in a double-blind,
      crossover design. The primary outcome of interest was sustained attention as
      assessed with hit reaction time variability (HRT-SD) on the identical pairs
      continuous performance test (CPT-IP). RESULTS: Mecamylamine worsened performance
      on CPT-IP HRT-SD, a measure of attention, compared to varenicline in both groups.
      Performance on mecamylamine was worse than performance on both placebo and
      varenicline on several additional measures of attention, including CPT-IP hit
      reaction time (HRT) and random errors at various levels of task difficulty. There
      was a treatment by diagnosis interaction, such that mecamylamine worsened
      performance on CPT-IP 2-digit HRT, 3-digit random errors, and 4-digit hit rate
      compared to placebo and varenicline in participants with schizophrenia; effects
      not observed in controls. CONCLUSIONS: These findings support a role for nAChRs
      in attention and suggest that those with schizophrenia may be particularly
      sensitive to nAChR blockade.

PMID- 24114426
TI  - Depression, impulsiveness, sleep, and memory in past and present polydrug users
      of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).
AB  - RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide
      recreational drug of abuse. Unfortunately, the results from human research
      investigating its psychological effects have been inconsistent. OBJECTIVES: The
      present study aimed to be the largest to date in sample size and 5HT-related
      behaviors; the first to compare present ecstasy users with past users after an
      abstinence of 4 or more years, and the first to include robust controls for other
      recreational substances. METHODS: A sample of 997 participants (52 % male) was
      recruited to four control groups (non-drug (ND), alcohol/nicotine (AN),
      cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy
      polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed
      a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness
      Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which,
      in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups
      tended to record greater deficits than the non-drug controls, the MDMA and EX
      MDMA groups recorded greater deficits than all the control groups on ten of the
      13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98;
      range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with
      present ecstasy users, the past users showed no change for ten measures,
      increased impairment for two measures, and improvement on just one measure.
      CONCLUSIONS: Given this record of impaired memory and clinically significant
      levels of depression, impulsiveness, and sleep disturbance, the prognosis for the
      current generation of ecstasy users is a major cause for concern.

PMID- 24114427
TI  - Time-dependent decreases in nucleus accumbens AMPA/NMDA ratio and incubation of
      sucrose craving in adolescent and adult rats.
AB  - RATIONALE AND OBJECTIVE: There is evidence that cue-induced sucrose seeking
      progressively increases after cessation of oral sucrose self-administration
      (incubation of sucrose craving) in both adolescent and adult rats. The synaptic
      plasticity changes associated with this incubation at different age groups are
      unknown. We assessed whether incubation of sucrose craving in rats trained to
      self-administer sucrose as young adolescents, adolescents, or adults is
      associated with changes in 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic
      acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio (a measure of postsynaptic changes
      in synaptic strength) in nucleus accumbens. METHODS: Three age groups initiated
      oral sucrose self-administration training (10 days) on postnatal day (P) 35
      (young adolescents), P42 (adolescents), or P70 (adults). They were then tested
      for cue-induced sucrose seeking (assessed in an extinction test) on abstinence
      days 1 and 21. Separate groups of rats were trained to self-administer sucrose or
      water (a control condition), and assessed for AMPA/NMDA ratio in nucleus
      accumbens on abstinence days 1-3 and 21. RESULTS: Adult rats earned more sucrose
      rewards, but sucrose intake per body weight was higher in young adolescent rats.
      Time-dependent increases in cue-induced sucrose seeking (incubation of sucrose
      craving) were more pronounced in adult rats, less pronounced in adolescents, and
      not detected in young adolescents. On abstinence day 21, but not days 1-3,
      AMPA/NMDA ratio in nucleus accumbens were decreased in rats that self
      administered sucrose as adults and adolescents, but not young adolescents.
      CONCLUSIONS: Our data demonstrate age-dependent changes in magnitude of
      incubation of sucrose craving and nucleus accumbens synaptic plasticity after
      cessation of sucrose self-administration.

PMID- 24114428
TI  - On the behavioural specificity of hypophagia induced in male rats by mCPP,
      naltrexone, and their combination.
AB  - RATIONALE: Serotonergic (5-hydroxytryptamine, 5-HT) and opioidergic mechanisms
      are intimately involved in appetite regulation. OBJECTIVES: In view of recent
      evidence of positive anorectic interactions between opioid and various non-opioid
      substrates, our aim was to assess the behavioural specificity of anorectic
      responses to the opioid receptor antagonist naltrexone, the 5-HT2C/1B receptor
      agonist mCPP and their combination. METHODS: Behavioural profiling techniques,
      including the behavioural satiety sequence (BSS), were used to examine acute drug
      effects in non-deprived male rats tested with palatable mash. Experiment 1
      characterised the dose-response profile of mCPP (0.1-3.0 mg/kg), while experiment
      2 assessed the effects of combined treatment with a sub-anorectic dose of mCPP
      (0.1 mg/kg) and one of two low doses of naltrexone (0.1 and 1.0 mg/kg). RESULTS:
      Experiment 1 confirmed the dose-dependent anorectic efficacy of mCPP, with robust
      effects on intake and feeding-related measures observed at 3.0 mg/kg. However,
      that dose was also associated with other behavioural alterations including
      increased grooming, reductions in locomotion and sniffing, and disruption of the
      BSS. In experiment 2, naltrexone dose-dependently reduced food intake and time
      spent feeding, effects accompanied by a behaviourally selective acceleration in
      the BSS. However, the addition of 0.1 mg/kg mCPP did not significantly alter the
      behavioural changes observed in response to either dose of naltrexone given
      alone. CONCLUSIONS: In contrast to recently reported positive anorectic
      interactions involving low-dose combinations of opioid receptor antagonists or
      mCPP with cannabinoid CB1 receptor antagonists, present results would not appear
      to provide any support for potentially clinically relevant anorectic interactions
      between opioid and 5-HT2C/1B receptor mechanisms.

PMID- 24114429
TI  - A study of N-methyl-D-aspartate receptor gene (GRIN2B) variants as predictors of
      treatment-resistant major depression.
AB  - RATIONALE: In clinical practice, ketamine, an antagonist of the N-methyl-D
      aspartate receptor (NMDAR), is used to alleviate depressive symptoms in patients
      with major depressive disorder (MDD), especially in those with treatment
      resistant depression (TRD). Accordingly, the human gene coding for the 2B subunit
      of the NMDAR (GRIN2B) is considered a promising candidate gene for MDD
      susceptibility. OBJECTIVES: The primary aim of this study is to examine whether
      potentially functional polymorphisms of GRIN2B confer risk for MDD, and second to
      investigate whether GRIN2B acts as a genetic predictor for TRD in MDD patients.
      METHODS: We enrolled 178 TRD and 612 non-TRD patients as well as 779 healthy
      controls. RESULTS: Four potentially functional polymorphisms (rs1805502, rs890,
      rs1806201, and rs7301328) within GRIN2B were genotyped in all participants. The
      haplotype analysis found significant differences in the distribution of the G-T
      haplotype between the TRD and control groups (corrected P = 0.007), and the
      frequency of the G-T haplotype in TRD group was significantly higher than that in
      the controls (TRD/control ratio 0.31:0.21). Statistically significant differences
      in allele and genotype frequencies were detected between TRD and non-TRD groups
      for the rs1805502 polymorphism within GRIN2B. There was a significant allelic
      association between rs1805502 and TRD with an excess of the G allele in the TRD
      group, compared to non-TRD group (OR = 1.55, 95 % CI = 1.18-2.05, corrected P =
      0.008). CONCLUSIONS: These initial findings strengthen the hypothesis that GRIN2B
      not only confers susceptibility to TRD, but also plays a genetic predictor for
      TRD in MDD patients.

PMID- 24114430
TI  - Treatment with a carbon monoxide-releasing molecule inhibits chronic inflammatory
      pain in mice: nitric oxide contribution.
AB  - RATIONALE: Carbon monoxide synthetized by inducible heme oxygenase (HO-1) exerts
      potent anti-inflammatory and antinociceptive effects during acute and neuropathic
      pain, but its role in the modulation of chronic inflammatory pain and the
      possible involvement of nitric oxide in this action remain unknown. OBJECTIVES
      AND METHODS: The antiallodynic and antihyperalgesic effects of a carbon monoxide
      releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), daily
      administered from days 4 to 14 after complete Freund's adjuvant (CFA) injection
      in wild-type (WT), neuronal (NOS1-KO), and inducible (NOS2-KO) nitric oxide
      synthases knockout mice, were evaluated using von Frey filaments and plantar
      tests. Effects of CORM-2 treatment on the expression of HO-1, NOS1, and NOS2 at
      14 days after inflammation induction were assessed by Western blot. RESULTS: Main
      inflammatory pain symptoms induced by CFA in WT, NOS1-KO, and NOS2-KO mice were
      significantly reduced in a time-dependent manner by CORM-2 treatment. In all
      genotypes, inflammation increased the dorsal root ganglia and paw expression of
      HO-1, but CORM-2 treatment only over-expressed this enzyme in the paw of all
      genotypes. The increased NOS1 expression induced by inflammation in WT mice was
      abolished by CORM-2 treatment, while there was no effect of the inflammation in
      neither CORM-2 treatment in the expression of NOS2 in WT and NOS1-KO mice.
      CONCLUSIONS: CORM-2 treatment inhibits inflammatory pain through enhancing HO-1
      paw expression in all genotypes and reducing NOS1 over-expression in WT mice. An
      interaction between HO-1/carbon monoxide and NOS1/nitric oxide systems was also
      demonstrated. CORM-2 treatment may represent a new approach for management
      chronic inflammatory pain.

PMID- 24114431
TI  - SNPs within the GH-signaling pathway are associated with the early IGF1 response
      to GH replacement therapy in GHD adults.
AB  - OBJECTIVE: GH-deficient (GHD) adults have reduced serum concentrations of IGF1.
      GH replacement therapy increases serum IGF1 concentrations, but the
      interindividual variation in treatment response is large and likely influenced by
      genetic factors. This study was designed to test the hypothesis that single
      nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway
      influence the serum IGF1 response to GH replacement. DESIGN AND METHODS: A total
      of 313 consecutive GHD adults (58.1% men; mean age 49.7 years) were studied
      before and after 1 week, 6 months, and 1 year of GH treatment. GH dose was
      individually titrated to normalize serum IGF1 levels. Six SNPs in the GH receptor
      (GHR) and the GH signaling pathway (JAK2, STAT5B, SOCS2, and PIK3CB) genes were
      selected for genotyping. The GHR exon 3-deleted/full-length (d3/fl) polymorphism
      was analyzed using tagSNP rs6873545. RESULTS: After 1 week of GH replacement,
      homozygotes of the fl-GHR showed a better IGF1 response to GH than carriers of
      the d3-GHR (P=0.016). Conversely, homozygotes of the minor allele of PIK3CB SNP
      rs361072 responded better than carriers of the major allele (P=0.025). Compared
      with baseline, both SNPs were associated with the IGF1 response at 6 months
      (P=0.041 and P=0.047 respectively), and SNP rs6873545 was further associated with
      the IGF1 response at 1 year (P=0.041). CONCLUSIONS: Our results indicate that
      common genetic variants in the GH signaling pathway may be of functional
      relevance to the response to GH replacement in GHD adults.

PMID- 24114432
TI  - Right ventricular and right atrial function and deformation in patients with
      subclinical hypothyroidism: a two- and three-dimensional echocardiographic study.
AB  - BACKGROUND: We sought to investigate right ventricular (RV) function and
      deformation assessed by three-dimensional echocardiography (3DE) and speckle
      tracking in patients with subclinical hypothyroidism (SHT), and to evaluate the
      influence of levothyroxine (L-T4) therapy on RV remodeling. METHODS: We included
      50 untreated women with SHT and 45 healthy control women matched by age. The L-T4
      therapy was prescribed to all SHT patients who were followed 1 year after
      euthyroid status was achieved. All study participants underwent laboratory
      analyses which included thyroid hormone levels, and complete two-dimensional
      echocardiography (2DE) and 3DE examinations. RESULTS: 3DE RV end-diastolic volume
      and ejection fraction were significantly reduced in the SHT patients before
      therapy in comparison with the healthy controls and treated SHT subjects. RV
      longitudinal strain, systolic, and early diastolic strain rates (SRs) were
      significantly decreased, whereas RV late diastolic SR was increased in the SHT
      patients before therapy when comparing with the controls. 2DE speckle tracking
      imaging revealed that L-T4 substitution therapy significantly improved RV
      systolic mechanics, whereas RV diastolic deformation was not completely
      recovered. Right atrial (RA) function and deformation were significantly impacted
      by SHT. Replacement L-T4 treatment improved but did not completely restore RA
      mechanics in the SHT patients. CONCLUSION: RV and RA function and mechanics are
      significantly affected by SHT. L-T4 therapy and 1-year maintenance of euthyroid
      status improved but did not completely recover RV and RA function and deformation
      in the SHT patients, which implies that right heart remodeling caused by SHT is
      not reversible in a 1-year period.

PMID- 24114433
TI  - Longitudinal trends in thyroid function in relation to iodine intake: ongoing
      changes of thyroid function despite adequate current iodine status.
AB  - OBJECTIVE: Several cross-sectional studies on populations with iodine deficiency
      showed that TSH-levels are negatively associated with age, while in populations
      with high iodine intake TSH is positively associated with age. The question is
      whether such an age-thyroid function relation is an ongoing process apparent also
      in longitudinal studies and whether it reflects an actual iodine deficiency or an
      iodine insufficiency in the past. METHODS: In an area with a borderline iodine
      status in the past, we studied 980 participants of the Nijmegen Biomedical Study.
      We measured serum TSH, free thyroxine (FT4), total triiodothyronine (T3),
      peroxidase antibodies, and the urine iodine and creatinine concentration 4 years
      after our initial survey of thyroid function, in which we reported a negative
      association between TSH and age. RESULTS: within 4 years, TSH decreased by 5.4%
      (95% ci 2.58.3%) and FT4 increased by 3.7% (95% ci 2.94.6%). median urinary
      iodine concentration was 130 MUg/l. estimated 24-h iodine excretion was not
      associated with TSH, T3, change of TSH, or FT4 over time or with the presence of
      antibodies against thyroid peroxidase. Only FT4 appeared to be somewhat higher at
      lower urine iodine levels: a 1.01% (95% CI 0.17-1.84%) higher FT4 for each lower
      iodine quintile. CONCLUSIONS: In this longitudinal study, we found an ongoing
      decrease in TSH and increase in FT4 in a previously iodine insufficient
      population, despite the adequate iodine status at present. This suggests that low
      iodine intake at young age leads to thyroid autonomy (and a tendency to
      hyperthyroidism) that persists despite normal iodine intake later in life.

PMID- 24114434
TI  - Improvement of selective screening strategy for gestational diabetes through a
      more accurate definition of high-risk groups.
AB  - OBJECTIVE: This study aimed to assess the predictive value of risk factors (RFs)
      for gestational diabetes mellitus (GDM) established by selective screening (SS)
      and to identify subgroups of women at a higher risk of developing GDM. DESIGN: A
      retrospective, single-center study design was employed. METHODS: Data of 1015
      women screened for GDM at 24-28 weeks of gestation and diagnosed according to the
      International Association of Diabetes and Pregnancy Study Groups criteria were
      evaluated. Information on RFs established by SS was also collected and their
      association with GDM was determined. To identify distinct and homogeneous
      subgroups of patients at a higher risk, the RECursive Partitioning and
      AMalgamation (RECPAM) method was used. RESULTS: Overall, 113 (11.1%) women were
      diagnosed as having GDM. The application of the SS criteria would result in the
      execution of an oral glucose tolerance test (OGTT) in 58.3% of women and 26
      (23.0%) cases of GDM would not be detected due to the absence of any RF. The
      RECPAM analysis identified high-risk subgroups characterized by fasting plasma
      glucose values >5.1 mmol/l (odds ratio (OR)=26.5; 95% CI 14.3-49.0) and pre
      pregnancy BMI (OR=7.0; 95% CI 3.9-12.8 for overweight women). In a final logistic
      model including RECPAM classes, previous macrosomia (OR=3.6; 95% CI 1.1-11.6),
      and family history of diabetes (OR=1.8; 95% CI 1.1-2.8), but not maternal age,
      were also found to be associated with an increased risk of developing GDM. A
      screening approach based on the RECPAM model would reduce by over 50% (23.0 vs
      10.6%) the number of undiagnosed GDM cases when compared with the current SS
      approach, at the expense of 50 additional OGTTs required. CONCLUSIONS: A
      screening approach based on our RECPAM model results in a significant reduction
      in the number of undetected GDM cases compared with the current SS procedure.

PMID- 24114435
TI  - Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone
      and somatostatin in postmenopausal women.
AB  - OBJECTIVE: Estrogen stimulates pulsatile secretion of GH, via mechanisms that are
      largely unknown. An untested hypothesis is that estradiol (E2) drives GH
      secretion by amplifying interactions among GH-releasing hormone (GHRH),
      somatostatin (SS), and GH-releasing peptide (GHRP). DESIGN: The design comprised
      double-blind randomized prospective administration of transdermal E2 vs placebo
      to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions
      for 13 h overnight with or without continuous GHRP2 stimulation. METHODS: End
      points were mean concentrations, deconvolved secretion, and approximate entropy
      (ApEn; a regularity measure) of GH. RESULTS: By generalized ANOVA models, it was
      observed that E2 vs placebo supplementation: i) augmented mean (13-h) GH
      concentrations (P=0.023), GHRH-induced pulsatile GH secretion over the first 3 h
      (P=0.0085) and pulsatile GH secretion over the next 10 h (P=0.054); ii) increased
      GHRP-modulated (P=0.022) and SS-modulated (P<0.001) GH ApEn; and iii) did not
      amplify GHRH/GHRP synergy during pulsatile GH secretion. By linear regression, E2
      concentrations were found to be positively correlated with GH secretion during
      GHRP2 infusion (P=0.022), whereas BMI was found to be negatively correlated with
      GH secretion during GHRH (P=0.006) and combined GHRH/GHRP (P=0.015) stimulation.
      E2 and BMI jointly determined triple (combined l-arginine, GHRH, and GHRP2)
      stimulation of GH secretion after saline (R2=0.44 and P=0.003) and pulsatile GHRH
      (R2=0.39 and P=0.013) infusions. CONCLUSION: In summary, in postmenopausal women,
      E2 supplementation augments the amount (mass) and alters the pattern (regularity)
      of GH secretion via interactions among GHRH, SS, GHRP, and BMI. These outcomes
      introduce a more complex model of E2 supplementation in coordinating GH secretion
      in aging women.

PMID- 24114436
TI  - Murder-suicide by carbon dioxide (CO2) poisoning: a family case from Berlin,
      Germany.
AB  - This report demonstrates how carbon dioxide (CO(2)) may be a potent weapon in
      murder-suicide, where the death scene offers virtually no clues as to the lethal
      modality and the autopsy findings are nonspecific. Four bodies were discovered in
      an apartment in midsummer 2012 in Berlin, Germany. The bodies were those of a
      father (a 69-year-old business consultant), his wife (aged 26-years), and two
      sons (aged 3 and 6 years, respectively). The police found the wife and two sons
      lying in their beds and the husband in a supine position on the floor with a
      plastic bag over his head tied loosely around his neck with a rope. A 500 g
      single-use CO(2) cylinder was standing on the floor. The container was almost
      empty and according to the label had been sold as a CO(2)-fertilizer for aquarium
      plants. Two synthetic inhalation face masks and tubing were also found, which
      tested positive for the DNA of all four deceased family members. It is
      hypothesized that the husband placed an inhalation mask over the mouths and noses
      of his wife and children while they were sleeping. Inhalation of pure CO(2)
      ensured their rapid unconsciousness due to hypercapnia and severe anoxia. The
      rapid increase in CO(2) concentration would render a victim helpless, with no
      time to wake and defend themselves, or others. The proximate cause of death in
      all cases was attributed to CO(2) intoxication, based on the scene findings, the
      reconstructed sequence of events, the autopsy, and results of toxicological
      studies.

PMID- 24114438
TI  - The self-report fecal incontinence and constipation questionnaire in patients
      with pelvic-floor dysfunction seeking outpatient rehabilitation.
AB  - BACKGROUND: Fecal incontinence and constipation affect men and women of all ages.
      OBJECTIVE: The purpose of this study was to psychometrically analyze the Fecal
      Incontinence and Constipation Questionnaire (FICQ) in patients seeking outpatient
      rehabilitation services due to pelvic-floor dysfunction (PFD). DESIGN: This was a
      retrospective analysis of cross-sectional data from 644 patients (mean age=52
      years, SD=16, range=18-91) being treated for PFD in 64 outpatient rehabilitation
      clinics in 20 states (United States). METHODS: We assessed the 20-item FICQ for
      unidimensionality and local independence, differential item functioning (DIF),
      item fit, item hierarchical structure, and test precision using an item response
      theory model. RESULTS: Factor analyses supported the 2-factor subscales as
      originally defined; items related to severity of leakage or constipation. Removal
      of 2 leakage items improved unidimensionality and local independence of the
      leakage scale. Among the remaining items, 2 items were suggestive of adjustment
      for DIF by age group and by number of PFD comorbid conditions. Item difficulties
      were suitable for patients with PFD with no ceiling or floor effect. Mean item
      difficulty parameters for leakage and constipation subscales ranged from 38.8 to
      62.3 and 28.1 to 63.3 (0-100 scale), respectively. Endorsed leakage items
      representing highest difficulty levels were related to delay defecation and
      confidence to control bowel leakage. Endorsed constipation items representing
      highest difficulty levels were related to the need to strain during a bowel
      movement and the frequency of bowel movements. LIMITATIONS: A limitation of this
      study was the lack of medical diagnostic criteria to classify patients.
      CONCLUSIONS: After removing 2 items and adjusting for DIF, the results supported
      sound psychometric properties of the FICQ items and its initial use for patients
      with PFD in outpatient rehabilitation services.

PMID- 24114437
TI  - Spinal Cord Injury Functional Ambulation Profile: a preliminary look at
      responsiveness.
AB  - BACKGROUND: The Spinal Cord Injury Functional Ambulation Profile (SCI-FAP) is a
      valid, reliable measure of walking skill (eg, walking while negotiating
      obstacles, doors, and stairs). OBJECTIVE: The responsiveness of the SCI-FAP was
      assessed at least 7 months after spinal cord injury (SCI) and compared with that
      of the 10-Meter Walk Test (10MWT) and the Six-Minute Walk Test (6MWT). DESIGN: A
      secondary analysis of data collected during a randomized, single-blind, crossover
      trial was performed. METHODS: Participants had incomplete SCI and could walk at
      least 5 m without manual assistance. After 3 or 4 baseline assessments,
      participants completed 2 months of precision training (stepping over obstacles
      and onto targets on the ground) and 2 months of endurance training (treadmill
      training with body weight support, if needed). Walking function was assessed with
      the SCI-FAP, 10MWT, and 6MWT. Internal responsiveness was evaluated through
      change scores and standardized response means (SRMs). External responsiveness was
      gauged by correlating change scores on the SCI-FAP, 10MWT, and 6MWT. The minimal
      detectable change was calculated from the standard error of measurement from the
      baseline assessments. RESULTS: The SCI-FAP scores improved with both
      interventions. The magnitude of change was greater for participants whose
      pretraining self-selected speed was less than 0.5 m/s. The SCI-FAP had moderate
      SRMs. The 10MWT (fastest speed) and 6MWT had the largest SRMs after precision
      training and endurance training, respectively. The minimal detectable change in
      the SCI-FAP was 96 points. LIMITATIONS: The convenience sample was small and all
      participants could ambulate independently (with devices); therefore, the
      generalizability of the findings is limited. CONCLUSIONS: The SCI-FAP was
      responsive to changes in walking ability in participants who had incomplete SCI
      and walked at slow speeds, but overall the 10MWT and 6MWT were more responsive.

PMID- 24114439
TI  - Long-term exercise training for an individual with mixed corticobasal
      degeneration and progressive supranuclear palsy features: 10-year case report
      follow-up.
AB  - BACKGROUND AND PURPOSE: This case report describes the effects of long-term (10
      year) participation in a community exercise program for a client with mixed
      features of corticobasal degeneration (CBD) and progressive supranuclear palsy
      (PSP). The effects of exercise participation on both functional status and brain
      volume are described. CASE DESCRIPTION: A 60-year-old male dentist initially
      reported changes in gait and limb coordination. He received a diagnosis of
      atypical CBD at age 66 years; PSP was added at age 72 years. At age 70 years, the
      client began a therapist-led community group exercise program for people with
      Parkinson disease (PD). The program included trunk and lower extremity stretching
      and strengthening, upright balance and strengthening, and both forward and
      backward treadmill walking. The client participated twice weekly for 1 hour for
      10 years and was reassessed in years 9 to 10. OUTCOMES: Falls (self-reported
      weekly over the 10-year period of the study by the client and his wife) decreased
      from 1.9 falls per month in year 1 to 0.3 falls per month in year 10. Balance,
      walking endurance, and general mobility declined slightly. Gait speed (both
      comfortable and fast) declined; the client was unable to vary gait speed.
      Quantitative brain measurements indicated a slow rate of whole brain volume loss
      and ventricular expansion compared with clients with autopsy-proven CBD or PSP.
      DISCUSSION: This client has participated consistently in a regular group exercise
      program for 10 years. He has reduced fall frequency, maintained balance and
      endurance, and retained community ambulation using a walker. Combined with the
      slow rate of brain volume loss, this evidence supports the efficacy of a regular
      exercise program to prolong longevity and maintain function in people with CBD or
      PSP.

PMID- 24114440
TI  - CT scan-measured pulmonary artery to aorta ratio and echocardiography for
      detecting pulmonary hypertension in severe COPD.
AB  - BACKGROUND: COPD is associated with significant morbidity primarily driven by
      acute exacerbations. Relative pulmonary artery (PA) enlargement, defined as a PA
      to ascending aorta (A) diameter ratio greater than one (PA:A>1) identifies
      patients at increased risk for exacerbations. However, little is known about the
      correlation between PA:A, echocardiography, and invasive hemodynamics in COPD.
      METHODS: A retrospective observational study of patients with severe COPD being
      evaluated for lung transplantation at a single center between 2007 and 2011 was
      conducted. Clinical characteristics, CT scans, echocardiograms, and right-sided
      heart catheterizations were reviewed. The PA diameter at the bifurcation and A
      diameter from the same CT image were measured. Linear and logistic regression
      were used to examine the relationships between PA:A ratio by CT scan and PA
      systolic pressure (PASP) by echocardiogram with invasive hemodynamics. Receiver
      operating characteristic analysis assessed the usefulness of the PA:A ratio and
      PASP in predicting resting pulmonary hypertension (PH) (mean pulmonary artery
      pressure [mPAP]>25 mm Hg). RESULTS: Sixty patients with a mean predicted FEV1 of
      27%+/-12% were evaluated. CT scan-measured PA:A correlated linearly with mPAP
      after adjustment for multiple covariates (r=0.30, P=.03), a finding not observed
      with PASP. In a multivariate logistic model, mPAP was independently associated
      with PA:A>1 (OR, 1.44; 95% CI, 1.02-2.04; P=.04). PA:A>1 was 73% sensitive and
      84% specific for identifying patients with resting PH (area under the curve,
      0.83; 95% CI, 0.72-0.93; P<.001), whereas PASP was not useful. CONCLUSIONS: A
      PA:A ratio>1 on CT scan outperforms echocardiography for diagnosing resting PH in
      patients with severe COPD.

PMID- 24114442
TI  - Two single nucleotide polymorphisms in the GDF5 gene are associated with
      development dysplasia of the hip in Chinese female population.

PMID- 24114441
TI  - Drug susceptibility of matrix-encapsulated Candida albicans nano-biofilms.
AB  - The rise in the use of biomedical devices and implants has seen a concomitant
      surge in the advent of device-related nosocomial (hospital-acquired) infections
      of bacterial and fungal origins. The most common nosocomial fungal infection is
      candidiasis caused mainly by Candida albicans biofilms. Candidiasis is associated
      with an unacceptably high mortality rate, and there is an urgent need for the
      discovery of new antifungal drugs that prevent or control biofilm formation. To
      this end, we recently developed an ultra-high-throughput microarray platform
      consisting of nano-scale biofilms of C. albicans encapsulated in collagen or
      alginate hydrogel matrices for antifungal drug screening. Here, we report that
      the choice of matrix influences the apparent susceptibility of C. albicans to the
      common antifungal drugs, amphotericin B, and caspofungin. While amphotericin B is
      equally effective against biofilms grown in collagen and alginate matrices,
      caspofungin is effective only against biofilms grown only in alginate, but not in
      collagen. We demonstrate differences in the distribution of the drugs in the two
      matrices may contribute to the susceptibility of C. albicans nano-biofilms. In a
      larger context, our results highlight the importance of the choice of matrix as a
      parameter in 3D cell encapsulation, and suggest a screening strategy to predict
      drug performance in vivo.

PMID- 24114443
TI  - Metabolic alteration in tumorigenesis.
AB  - Altered metabolism in cancer was first discovered by Otto Warburg early last
      century. Although the Warburg Effect has been widely used in tumor detection,
      relatively little progress had been made in mechanistic understanding of cancer
      metabolism in the subsequent eight decades. Genetic studies have recently
      identified mutations in human cancer targeting multiple enzymes involved in
      intermediate metabolism. One emerging mechanism common to these mutant enzymes is
      the accumulation of a metabolite that alters the epigenetic control. 

PMID- 24114444
TI  - Platelet proteomics and its advanced application for research of blood stasis
      syndrome and activated blood circulation herbs of Chinese medicine.
AB  - The development of novel and efficient antiplatelet agents that have few adverse
      effects and methods that improve antiplatelet resistance has long been the focus
      of international research on the prevention and treatment of cardiovascular and
      cerebrovascular diseases. Recent advances in platelet proteomics have provided a
      technology platform for high-quality research of platelet pathophysiology and the
      development of new antiplatelet drugs. The study of blood stasis syndrome (BSS)
      and activated blood circulation of traditional Chinese medicine (TCM) is one of
      the most active fields where the integration of TCM and western medicine in China
      has been successful. Activated blood circulation herbs (ABC herbs) of Chinese
      medicine are often used in the treatment of BSS. Most ABC herbs have antiplatelet
      and anti-atherosclerosis activity, but knowledge about their targets is lacking.
      Coronary heart disease (CHD), BSS, and platelet activation are closely related.
      By screening and identifying activated platelet proteins that are differentially
      expressed in BSS of CHD, platelet proteomics has helped researchers interpret the
      antiplatelet mechanism of action of ABC herbs and provided many potential
      biomarkers for BSS that could be used to evaluate the clinical curative effect of
      new antiplatelet drugs. In this article the progress of platelet proteomics and
      its advanced application for research of BSS and ABC herbs of Chinese medicine
      are reviewed. 

PMID- 24114445
TI  - Frequency of HLA-A 03 associates with HIV-1 infection in a Chinese cohort.
AB  - During the early mid-1990s, a number of rural farmers across central China were
      employed to the unregulated plasmaselling-activity and many of them were infected
      by HIV-1. However, AIDS progression in the former blood donors (FBDs) is various.
      The aim of this study is to assess human leukocyte antigen (HLA) class I allele
      distribution in FBDs and evaluate its association with HIV-1 infection and
      disease progression. A total of 353 FBDs were enrolled in the cohort including
      294 ART naive HIV-1 seropositive and 59 HIV-1 seronegative age-matched subjects.
      The viral load and CD4/CD8 T cell counts were assessed in all subjects. Compared
      with HIV-seropositive group, the frequency of HLA-A 03 in control was
      significantly higher. After classifying the HLA-B alleles of the subjects
      according to the presence of Bw4/Bw6 serological epitopes, detrimental effect of
      HLA Bw6/ Bw6 homozygosity was also confirmed in the HIV-seropositive subjects.
      This study provides novel evidence on HLA class I allele distribution and
      association of HLA-A 03 frequency with HIV-1 infection and viremia in the HIV-1
      infected FBDs, which may throw light on intervention strategy for the HIV-1
      infection and our understanding how host immunity and genetic background affect
      HIV infection and AIDS progression.

PMID- 24114446
TI  - Yeast nutrient transceptors provide novel insight in the functionality of
      membrane transporters.
AB  - In the yeast Saccharomyces cerevisiae several nutrient transporters have been
      identified that possess an additional function as nutrient receptor. These
      transporters are induced when yeast cells are starved for their substrate, which
      triggers entry into stationary phase and acquirement of a low protein kinase A
      (PKA) phenotype. Re-addition of the lacking nutrient triggers exit from
      stationary phase and sudden activation of the PKA pathway, the latter being
      mediated by the nutrient transceptors. At the same time, the transceptors are
      ubiquitinated, endocytosed and sorted to the vacuole for breakdown. Investigation
      of the signaling function of the transceptors has provided a new read-out and new
      tools for gaining insight into the functionality of transporters. Identification
      of amino acid residues that bind co-transported ions in symporters has been
      challenging because the inactivation of transport by site-directed mutagenesis is
      not conclusive with respect to the cause of the inactivation. The discovery of
      nontransported agonists of the signaling function in transceptors has shown that
      transport is not required for signaling. Inactivation of transport with
      maintenance of signaling in transceptors supports that a true proton-binding
      residue was mutagenised. Determining the relationship between transport and
      induction of endocytosis has also been challenging, since inactivation of
      transport by mutagenesis easily causes loss of all affinity for the substrate.
      The use of analogues with different combinations of transport and signaling
      capacities has revealed that transport, ubiquitination and endocytosis can be
      uncoupled in several unexpected ways. The results obtained are consistent with
      transporters undergoing multiple substrate-induced conformational changes, which
      allow interaction with different accessory proteins to trigger specific
      downstream events. 

PMID- 24114447
TI  - Emodin-6-O-beta-D--glucoside inhibits high-glucose-induced vascular inflammation.
AB  - Emodin-6-O-beta-D-glucoside (EG), a new active compound from Reynoutria japonica,
      has recently been shown to exert potent anti-inflammatory and barrier protective
      effects in human umbilical vein endothelial cells (HUVECs) and in mice. Vascular
      inflammatory process has been suggested to play a key role in initiation and
      progression of atherosclerosis, a major complication of diabetes mellitus. Thus,
      we attempted to determine whether EG can suppress the vascular inflammatory
      process induced by high glucose (HG) in HUVECs and mice. Data showed that HG
      induced markedly increased vascular permeability, monocyte adhesion, expressions
      of CAMs, formation of ROS, and activation of NF-kappaB. Remarkably, all of the
      above-mentioned vascular inflammatory effects of HG were attenuated by
      pretreatment with EG. Vascular inflammatory responses induced by HG are critical
      events underlying development of various diabetic complications; therefore, our
      results suggest that EG may have significant therapeutic benefits against
      diabetic complications and atherosclerosis. 

PMID- 24114448
TI  - Long-term stability of uveitis with faint anterior chamber flare treated with
      once-daily topical ophthalmic betamethasone.
AB  - The aim of our study is to investigate the long-term transitions of intraocular
      pressure (IOP) and aqueous flare values in uveitis patients with faint anterior
      chamber flare who were treated with once-daily topical ophthalmic betamethasone
      for more than 6 months. The study included a total of 111 eyes of 68 outpatients.
      The mean follow-up period was 26.8 months. The average IOP and aqueous flare
      value of patients divided by the 5-months follow-up period showed no significant
      difference. Six eyes (of four patients) were followed-up for more than 1 year
      after termination of the treatment. Among these patients, the average aqueous
      flare value was significantly higher, and the average period to reach more than
      1.5 times the former aqueous flare value significantly decreased after
      termination than before. Once-daily topical ophthalmic betamethasone is not
      expected to cause steroid-induced ocular hypertension but to have prophylactic
      effect.

PMID- 24114449
TI  - Is extrapolation of the safety and efficacy data in one indication to another
      appropriate for biosimilars?
AB  - CT-P13, the world's first biosimilar monoclonal antibody to infliximab, was
      approved for marketing in South Korea for all the six indications of infliximab,
      which Europe may follow, although the product was tested only in rheumatoid
      arthritis (RA) with a limited pharmacokinetic comparison in ankylosing
      spondylitis. However, the extrapolation of the efficacy and safety findings of CT
      P13 in RA to the other indications appears scientifically challenging when
      assessed by the current regulatory requirements. RA is not a sensitive clinical
      model to detect potential differences between CT-P13 and infliximab, and other
      mechanisms of action than antagonizing tumor necrosis factor alpha appear to be
      also important, which could be different by the approved indications.
      Furthermore, the immunogenicity and safety profiles of CT-P13 were not
      sufficiently characterized in that immunogenicity potential was lowest in RA,
      which was even further suppressed by the concomitant use of methotrexate.
      Extrapolation of the safety and efficacy data in one indication to another may be
      inappropriate for biosimilars unless backed up by strong scientific
      justification, which may include the mechanistic exposure-relationship approach.
      Therefore, regulatory agencies need to exercise caution before granting
      extrapolated indications to biosimilars. 

PMID- 24114451
TI  - Response to letter regarding article, "Urgent best medical therapy may obviate
      the need for urgent surgery in patients with symptomatic carotid stenosis".

PMID- 24114450
TI  - Impact of epigenetic dietary compounds on transgenerational prevention of human
      diseases.
AB  - The etiology of most human diseases involves complicated interactions of multiple
      environmental factors with individual genetic background which is initially
      generated early in human life, for example, during the processes of embryogenesis
      and fetal development in utero. Early embryogenesis includes a series of
      programming processes involving extremely accurate time-controlled gene
      activation/silencing expressions, and epigenetic control is believed to play a
      key role in regulating early embryonic development. Certain dietary components
      with properties in influencing epigenetic processes are believed to have
      preventive effects on many human diseases such as cancer. Evidence shows that in
      utero exposure to certain epigenetic diets may lead to reprogramming of primary
      epigenetic profiles such as DNA methylation and histone modifications on the key
      coding genes of the fetal genome, leading to different susceptibility to diseases
      later in life. In this review, we assess the current advances in dietary
      epigenetic intervention on transgenerational human disease control. Enhanced
      understanding of the important role of early life epigenetics control may lead to
      cost-effective translational chemopreventive potential by appropriate
      administration of prenatal and/or postnatal dietary supplements leading to early
      disease prevention. 

PMID- 24114452
TI  - Age and ethnic disparities in incidence of stroke over time: the South London
      Stroke Register.
AB  - BACKGROUND AND PURPOSE: Data on continuous monitoring of stroke risk among
      different age and ethnic groups are lacking. We aimed to investigate age and
      ethnic disparities in stroke incidence over time from an inner-city population
      based stroke register. METHODS: Trends in stroke incidence and before-stroke risk
      factors were investigated with the South London Stroke Register, a population
      based register covering a multiethnic population of 357 308 inhabitants. Age-,
      ethnicity-, and sex-specific incidence rates with 95% confidence intervals were
      calculated, assuming a Poisson distribution and their trends over time tested by
      the Cochran-Armitage test. RESULTS: Four thousand two hundred forty-five patients
      with first-ever stroke were registered between 1995 and 2010. Total stroke
      incidence reduced by 39.5% during the 16-year period from 247 to 149.5 per 100
      000 population (P<0.0001). Similar declines in stroke incidence were observed in
      men, women, white groups, and those aged>45 years, but not in those aged 15 to 44
      years (12.6-10.1; P=0.2034) and black groups (310.1-267.5; P=0.3633). The mean
      age at stroke decreased significantly from 71.7 to 69.6 years (P=0.0001). The
      reduction in prevalence of before-stroke risk factors was mostly seen in white
      patients aged>55 years, whereas an increase in diabetes mellitus was observed in
      younger black patients aged 15 to 54 years. CONCLUSIONS: Total stroke incidence
      decreased during the 16-year time period. However, this was not seen in younger
      age groups and black groups. The advances in risk factor reduction observed in
      white groups aged>55 years failed to be transferred to younger age groups and
      black groups.

PMID- 24114453
TI  - IMS-III and SYNTHESIS Expansion trials of endovascular therapy in acute ischemic
      stroke: how can we improve?

PMID- 24114454
TI  - Intra-arterial delivery is not superior to intravenous delivery of autologous
      bone marrow mononuclear cells in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Bone marrow-derived mononuclear cells (MNCs) are an
      investigational autologous cell-based therapy for acute ischemic stroke. Both
      intravenous (IV) and intra-arterial (IA) administration routes have been used in
      clinical trials. However, the route of administration to optimize the effect of
      MNCs is unknown. In this study, we compared the effect of IV versus IA route of
      administration of MNCs in the rat stroke model. METHODS: Long Evans rats were
      subjected to transient middle cerebral artery occlusion. At 24 hours after
      stroke, animals were randomly assigned to receive autologous bone marrow-derived
      MNCs using either the IV or IA delivery route. IV saline served as control. One
      million cells/kg (low dose) and 30 million cells/kg (high dose) were assessed.
      Neurological testing, cavity size, serum cytokines, neuroregenerative end points,
      and MNC biodistribution were evaluated. RESULTS: High-dose MNCs improved
      functional recovery, reduced lesion size and proinflammatory cytokines, and
      increased vessel density and neurogenesis markers compared with saline treatment
      (P<0.05). However, there were no significant differences between IV and IA MNC
      treated groups, although IV MNCs reduced serum interleukin-1beta levels compared
      with IA MNCs (P<0.05). IA MNCs at high dose led to a greater number of cells in
      the brain at 1 and 6 hours after injection but not in the lungs and spleen. Low
      dose MNCs (by IV or IA) did not improve any functional or structural end point
      compared with saline. CONCLUSIONS: At low and high doses of MNCs, we found that
      IV or IA achieves similar structural and functional outcomes after stroke.

PMID- 24114455
TI  - Letter by Naylor regarding article, "Urgent best medical therapy may obviate the
      need for urgent surgery in patients with symptomatic carotid stenosis".

PMID- 24114456
TI  - Combined 18F-FDG PET-CT and DCE-MRI to assess inflammation and
      microvascularization in atherosclerotic plaques.
AB  - BACKGROUND AND PURPOSE: Hallmarks of vulnerable atherosclerotic plaques are
      inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron
      emission tomography/computed tomography, and increased neovascularization that
      can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether
      these parameters are correlated or represent independent imaging parameters. This
      study determines whether there is a correlation between inflammation and
      neovascularization in atherosclerotic carotid plaques. METHODS: A total of 58
      patients with transient ischemic attack or minor stroke in the carotid territory
      and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients
      underwent positron emission tomography/computed tomography and dynamic contrast
      enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake
      values with target/background ratio were determined. Neovascularization was
      quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank
      correlation coefficients between target/background ratio and Ktrans were
      calculated. RESULTS: Images suitable for further analysis were obtained in 49
      patients. A weak but significant positive correlation between target/background
      ratio and mean Ktrans (Spearman rho=0.30 [P=0.035]) and 75th percentile Ktrans
      (Spearman rho=0.29 [P=0.041]) was found. CONCLUSIONS: There is a weak but
      significant positive correlation between inflammation on positron emission
      tomography/computed tomography and neovascularization as assessed with dynamic
      contrast-enhanced-MRI. Future studies should investigate which imaging modality
      has the highest predictive value for recurrent stroke, as these are not
      interchangeable. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00451529.

PMID- 24114459
TI  - Substrate oscillations boost recombinant protein release from Escherichia coli.
AB  - Intracellular production of recombinant proteins in prokaryotes necessitates
      subsequent disruption of cells for protein recovery. Since the cell disruption
      and subsequent purification steps largely contribute to the total production
      cost, scalable tools for protein release into the extracellular space is of
      utmost importance. Although there are several ways for enhancing protein release,
      changing culture conditions is rather a simple and scalable approach compared to,
      for example, molecular cell design. This contribution aimed at quantitatively
      studying process technological means to boost protein release of a periplasmatic
      recombinant protein (alkaline phosphatase) from E. coli. Quantitative analysis of
      protein in independent bioreactor runs could demonstrate that a defined
      oscillatory feeding profile was found to improve protein release, about 60 %,
      compared to the conventional constant feeding rate. The process technology
      included an oscillatory post-induction feed profile with the frequency of 4 min.
      The feed rate was oscillated triangularly between a maximum (1.3-fold of the
      maximum feed rate achieved at the end of the fed-batch phase) and a minimum (45 %
      of the maximum). The significant improvement indicates the potential to maximize
      the production rate, while this oscillatory feed profile can be easily scaled to
      industrial processes. Moreover, quantitative analysis of the primary metabolism
      revealed that the carbon dioxide yield can be used to identify the preferred
      feeding profile. This approach is therefore in line with the initiative of
      process analytical technology for science-based process understanding in process
      development and process control strategies. 

PMID- 24114458
TI  - Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive
      impairment in subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) can leave patients with
      memory impairments that may not recover fully. Molecular mechanisms are poorly
      understood, and no treatment is available. The sulfonylurea receptor 1-transient
      receptor potential melastatin 4 (Sur1-Trpm4) channel plays an important role in
      acute central nervous system injury. We evaluated upregulation of Sur1-Trpm4 in
      humans with SAH and, in rat models of SAH, we examined Sur1-Trpm4 upregulation,
      its role in barrier dysfunction and neuroinflammation, and its consequences on
      spatial learning. METHODS: We used Forster resonance energy transfer to detect
      coassociated Sur1 and Trpm4 in human autopsy brains with SAH. We studied rat
      models of SAH involving filament puncture of the internal carotid artery or
      injection of blood into the subarachnoid space of the entorhinal cortex. In rats,
      we used Forster resonance energy transfer and coimmunoprecipitation to detect
      coassociated Sur1 and Trpm4, we measured immunoglobulin G extravasation and tumor
      necrosis alpha overexpression as measures of barrier dysfunction and
      neuroinflammation, and we assessed spatial learning and memory on days 7 to 19.
      RESULTS: Sur1-Trpm4 channels were upregulated in humans and rats with SAH. In
      rats, inhibiting Sur1 using antisense or the selective Sur1 inhibitor
      glibenclamide reduced SAH-induced immunoglobulin G extravasation and tumor
      necrosis alpha overexpression. In models with entorhinal SAH, rats treated with
      glibenclamide for 7 days after SAH exhibited better platform search strategies
      and better performance on incremental and rapid spatial learning than vehicle
      treated controls. CONCLUSIONS: Sur1-Trpm4 channels are upregulated in humans and
      rats with SAH. Channel inhibition with glibenclamide may reduce neuroinflammation
      and the severity of cognitive deficits after SAH.

PMID- 24114460
TI  - Acetone-butanol-ethanol production from corn stover pretreated by alkaline twin
      screw extrusion pretreatment.
AB  - In this study, the alkaline twin-screw extrusion pretreated corn stover was
      subjected to enzymatic hydrolysis after washing. The impact of solid loading and
      enzyme dose on enzymatic hydrolysis was investigated. It was found that 68.2 g/L
      of total fermentable sugar could be obtained after enzymatic hydrolysis with the
      solid loading of 10 %, while the highest sugar recovery of 91.07 % was achieved
      when the solid loading was 2 % with the cellulase dose of 24 FPU/g substrate.
      Subsequently, the hydrolyzate was fermented by Clostridium acetobutylicum ATCC
      824. The acetone-butanol-ethanol (ABE) production of the hydrolyzate was compared
      with the glucose, xylose and simulated hydrolyzate medium which have the same
      reducing sugar concentration. It was shown that 7.1 g/L butanol and 11.2 g/L ABE
      could be produced after 72 h fermentation for the hydrolyzate obtained from
      enzymatic hydrolysis with 6 % solid loading. This is comparable to the glucose
      and simulated hydrozate medium, and the overall ABE yield could reach 0.112 g/g
      raw corn stover. 

PMID- 24114461
TI  - Short-term impact of low-dose atorvastatin on serum proprotein convertase
      subtilisin/kexin type 9.
AB  - BACKGROUND AND OBJECTIVE: Several small studies have found that moderate- to high
      dose statins (HMG-CoA reductase inhibitors) could increase the serum proprotein
      convertase subtilisin/kexin type 9 (PCSK9) level. However, little is known
      regarding the short-term, dose-dependent effects of low-dose atorvastatin and the
      rapid effects of a single dose of atorvastatin on PCSK9. The objective of this
      study was to investigate the short-term impact of low-dose atorvastatin on PCSK9
      in humans. METHODS: In this randomized study, data from 66 subjects were
      analyzed. In protocol I, 32 patients were randomized to atorvastatin 10 mg/day (n
      = 19) or 20 mg/day (n = 13) and eight healthy subjects without therapy were
      controls for 8 weeks. Serum PCSK9 and lipid profile were determined at day 0,
      week 4, and week 8. In protocol II, 26 patients were randomized to a single dose
      of atorvastatin 10 mg (n = 11) or 80 mg (n = 15), and serum levels of PCSK9 were
      measured at 24 h after treatment. RESULTS: Atorvastatin 10 mg/day decreased low
      density lipoprotein cholesterol (LDL-C) by 32 % at 4 weeks and by 33 % at 8
      weeks, and atorvastatin 20 mg/day resulted in reduction of LDL-C by 41 % at 4
      weeks and by 38 % at 8 weeks. Atorvastatin 10 mg/day slightly increased serum
      PCSK9 by 5-7 % but without a significant difference, while atorvastatin 20 mg/day
      significantly increased serum PCSK9 by 30 % at 4 weeks and by 35 % at 8 weeks (p
      = 0.009 and p = 0.002, respectively). In addition, 24 h after a single dose,
      atorvastatin 10 mg significantly increased serum PCSK9 by 13 % and atorvastatin
      80 mg by 27 % (p = 0.042 and p = 0.001, respectively). CONCLUSION: The short-term
      impact of low-dose atorvastatin on PCSK9 was time and dose dependent, with a
      rapid increase in PCSK9 levels being observed within 24 h of dosing.

PMID- 24114462
TI  - Monounsaturated fatty acids in serum triacylglycerols are associated with
      response to neoadjuvant chemotherapy in breast cancer patients.
AB  - Changes in cellular lipid metabolism are a common feature in most solid tumors,
      which occur already in early stages of the tumor progression. However, it remains
      unclear if the tumor-specific lipid changes can be detected at the level of
      systemic lipid metabolism. The objective of this study was to perform
      comprehensive analysis of lipids in breast cancer patient serum samples.
      Lipidomic profiling using an established analytical platform was performed in two
      cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The
      analyses were performed for 142 patients before and after neoadjuvant
      chemotherapy, and the results before chemotherapy were validated in an
      independent cohort of 194 patients. The analyses revealed that in general the
      tumor characteristics are not reflected in the serum samples. However, there was
      an association of specific triacylglycerols (TGs) in patients' response to
      chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower
      levels in those patients showing pathologic complete response before receiving
      chemotherapy. Some of these TGs were also associated with estrogen receptor
      status and overall or disease-free survival of the patients. The results suggest
      that the altered serum levels of oleic acid in breast cancer patients are
      associated with their response to chemotherapy. 

PMID- 24114463
TI  - Functional communication training with and without alternative reinforcement and
      punishment: an analysis of 58 applications.
AB  - Functional communication training (FCT) is an empirically supported treatment for
      problem behavior displayed by individuals with intellectual disabilities.
      Hagopian, Fisher, Sullivan, Acquisto, and LeBlanc (1998) analyzed 25 applications
      of FCT and showed that extinction was a necessary component of FCT, but sometimes
      punishment was needed to maintain low levels of problem behavior. The current
      consecutive case series summarized data from 58 applications of FCT in more
      recent cases. This analysis extended and updated Hagopian et al. by examining FCT
      when used in combination with alternative reinforcement (noncontingent and
      differential reinforcement) and multiple schedules during schedule thinning.
      Although it is difficult to make direct comparisons with the 1998 study, the
      results of the current case series analysis suggest that FCT can be enhanced when
      used in combination with alternative reinforcement and when multiple schedules
      are used during schedule thinning. 

PMID- 24114464
TI  - Questioning the use of privately-owned apes in anthropological research.

PMID- 24114465
TI  - Structural screening by multiple reaction monitoring as a new approach for tandem
      mass spectrometry: presented for the determination of pyrrolizidine alkaloids in
      plants.
AB  - In tandem mass spectrometry the multiple reaction monitoring (MRM) mode is
      normally used for targeted analysis but this mode also has the potential to
      screen for structural similarities of analytes. On the basis of the fact that in
      general similar molecular structures result in similar fragments or losses of
      neutrals, this approach was used for pyrrolizidine alkaloid (PA) screening but
      could also be easily adapted to screen for other compound classes. PA are plant
      toxins of which several hundred individual compounds have been identified. Our
      MRM screening approach uses the structural relation and similar core structure of
      all PA which results in a common and thus predictable mass spectrometric
      fragmentation behaviour. On this basis a method was developed which screens for
      PA structures by MRM transitions and allows the detection of each individual PA
      down to a low microgram per kilogram concentration range. The approach was
      applied to investigate plants from the families of Asteraceae (several species of
      Senecio and Eupatorium), Boraginaceae (Echium, Cynoglossum, Borago and Anchusa
      officinalis as well as Heliotropium europaeum) and Fabaceae (Crotalaria incana)
      for a complete qualitative and quantitative PA characterisation. All analytes
      that were detected as possible PA by MRM screening were further investigated by
      recording product ion spectra. Analytes which exhibited a typical PA
      fragmentation pattern were either confirmed as PA or otherwise deleted as false
      positive signals (false positive rate was below 10 %). Sum formulas of confirmed
      PA were determined by additional measurements applying high resolution mass
      spectrometry. In that way 121 unknown PA were identified and for the first time
      complete PA profiles of different PA plants were delivered. 

PMID- 24114466
TI  - A sensitive and selective LC-MS/MS analysis coupled with an online sample
      enrichment technique for H295R steroidogenesis assay and its application in the
      investigation of the effect of sildenafil on steroidogenesis.
AB  - An in vitro steroidogenesis assay using H295R human adenocarcinoma cells is a
      useful tool for the fast identification of compounds that affect the production
      of testosterone and 17beta-estradiol. Selective and sensitive hormone measurement
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can make this assay
      more reliable. Therefore, in the present study, a sensitive and selective method
      for the quantification of testosterone and 17beta-estradiol in the H295R
      steroidogenesis assay was developed and fully validated using LC-MS/MS coupled
      with an online sample enrichment technique. To prove its usefulness, the method
      developed was applied to investigate the effect of sildenafil on steroidogenesis.
      Cell medium samples were diluted and prepared using solid-phase extraction. The
      samples were prepared on ice and were not kept for more than 30 min to prevent
      degradation of hormones. The extracts were dried, reconstituted, filtered, and
      analyzed by LC-MS/MS with polarity switching electrospray ionization. The
      validation results for selectivity, matrix effect, recovery, linearity,
      precision, and accuracy were satisfactory. The limits of detection for
      testosterone and 17beta-estradiol were 5 and 10 pg/mL, respectively, and the
      limit of quantification for both testosterone and 17beta-estradiol was 10 pg/mL,
      which was in accordance with the OECD guideline. No degradation was observed
      under the storage conditions for 7 and 14 days at -80  degrees C as well as after
      three freeze-thaw cycles, whereas 17beta-estradiol was degraded after 1 h on ice
      during sample processing. The method developed was successfully used for the
      investigation of the effect of sildenafil on steroidogenesis. This method can be
      very useful for the initial selection of drugs with androgenic and/or estrogenic
      effects for specific purposes, e.g., in the selection of drugs that are used to
      reverse the effects of chemical castration.

PMID- 24114467
TI  - Comparison of retention behavior of oligolysine and oligoarginine in ion-pairing
      chromatography using heptafluorobutyric acid.
AB  - This paper describes the retention behavior of oligolysine and oligoarginine
      peptides of different lengths as a function of heptafluorobutyric acid (HFBA)
      concentration in ion-pairing reversed-phase chromatography in isocratic elution.
      A mixture of oligolysine and a mixture of oligoarginine with number of amino acid
      residues (dp) from two to eight were conveniently prepared by one-pot protease
      catalyzed synthesis. Analysis of the logarithm of the retention factor k as a
      function of [HFBA] for each oligopeptide component, using a closed pairing model,
      provided values for (1) number (n) of paired HFBA anions per peptide molecule,
      (2) equilibrium constant (K(ip,m)) for ion pairing between oligopeptides and HFBA
      anions, and (3) product of the phase ratio and the distribution constant of the
      paired oligopeptide between the mobile and stationary phases (betaK(d,ip)). We
      found that betaK(d,ip) of oligoarginine is larger compared with oligolysine
      having the same dp. A linear relationship was obtained for ln betaK(d,ip) as a
      function of n + g . dp. By optimizing constant g separately for oligolysine and
      oligoarginine, we determined that g is larger for oligoarginine, in agreement
      with the higher hydrophobicity of arginine residues. Plotting the fraction of
      paired oligoarginine and oligolysine as a function of [HFBA] shows that the
      cooperative effect in forming ion pairs is greater for oligoarginine than
      oligolysine.

PMID- 24114468
TI  - [Foot lesions].
AB  - The foot is the target organ of a variety of internal diseases. Of upmost
      importance is the diabetic foot syndrome (DFS). Its complex pathophysiology is
      driven by the diabetic neuropathy, a vastly worsening effect is contributed by
      infection and ischemia. Seemingly localised lesions have the potential for
      phlegmone and septicaemia if not diagnosed and drained early. The acral lesions
      of peripheral artery occlusive disease (PAOD) have unique features as well.
      However, their life-threatening potential is lower than that of DFS even if the
      limb is critical. Notably, isolated foot lesions with a mere venous cause may
      arise from insufficient perforator veins; the accompanying areas of
      haemosiderosis will lead the diagnostic path. Cholesterol embolization (blue toe
      syndrome, trash foot) elicits a unique clinical picture and will become more
      frequent with increasing numbers of catheter-based procedures. Finally,
      descriptions are given of podagra and of foot mycosis as disease entities not
      linked to perfusion. The present review focuses on the depiction of disease and
      its diagnosis, leaving therapeutic considerations untouched. 

PMID- 24114469
TI  - 1.2 A X-ray structure of the renal potassium channel Kv1.3 T1 domain.
AB  - Here we present the structure of the T1 domain derived from the voltage-dependent
      potassium channel K(v)1.3 of Homo sapiens sapiens at 1.2 A resolution
      crystallized under near-physiological conditions. The crystals were grown without
      precipitant in 150 mM KP(i), pH 6.25. The crystals show I4 symmetry typical of
      the natural occurring tetrameric assembly of the single subunits. The obtained
      structural model is based on the highest resolution currently achieved for
      tetramerization domains of voltage-gated potassium channels. We identified an
      identical fold of the monomer but inside the tetramer the single monomers show a
      significant rotation which leads to a different orientation of the tetramer
      compared to other known structures. Such a rotational movement inside the
      tetrameric assembly might influence the gating properties of the channel. In
      addition we see two distinct side chain configurations for amino acids located in
      the top layer proximal to the membrane (Tyr109, Arg116, Ser129, Glu140, Met142,
      Arg146), and amino acids in the bottom layer of the T1-domain distal from the
      membrane (Val55, Ile56, Leu77, Arg86). The relative populations of these two
      states are ranging from 50:50 for Val55, Tyr109, Arg116, Ser129, Glu140, 60:40
      for Met142, 65:35 for Arg86, 70:30 for Arg146, and 80:20 for Ile56 and Leu77. The
      data suggest that in solution these amino acids are involved in an equilibrium of
      conformational states that may be coupled to the functional states of the whole
      potassium channel.

PMID- 24114470
TI  - Cloning, expression, and characterization of a methionine sulfoxide reductase B
      gene from Nicotiana tabacum.
AB  - Reactive oxygen species (ROS) are generated during normal aerobic metabolism and
      in plants exposed to environmental stress. Methionine (Met) residues are
      particularly sensitive to ROS-mediated oxidation, leading to the formation of
      methionine sulfoxide (MetSO) under mild oxidative conditions. Methionine
      sulfoxide reductase (MSR) repairs oxidized Met and protects plants from oxidative
      damage. Herein, we identified a tobacco (Nicotiana tabacum) MSRB gene, referred
      to as NtMSRB3. Analysis of the sequence showed that the NtMSRB3 protein had four
      typical motifs in a SelR domain, which is known as the catalytic region of MSRBs.
      NtMSRB3 specifically reduced the R epimer of MetSO and converted either free
      MetSO or Dabsyl-MetSO in the presence of dithiothreitol. Escherichia coli cells
      harboring NtMSRB3 displayed relative high viability under H2O2 stress.
      Subcellular localization of NtMSRB3 revealed that it was a plastid-targeted
      protein. Furthermore, the semi-quantitative reverse transcription polymerase
      chain reaction assay showed that NtMSRB3 was upregulated apparently by abscisic
      acid, salt, cold, and methyl viologen stress within 24 h of treatment.

PMID- 24114471
TI  - The role of metabolic carcinogenesis in cancer causation and prevention: evidence
      from the European Prospective Investigation into Cancer and Nutrition.
AB  - The theory that nutrition might be involved in the causation and prevention of
      cancer arose over 100 years ago from laboratory studies of the effect of diet on
      tumour growth. During the mid-20th century, the major focus of cancer
      epidemiology was on the role of tobacco and alcohol. It was not until the early
      1980s, following a seminal report from Doll and Peto on cancer causes, that major
      research programmes on nutrition and cancer were instigated. The European
      Prospective Investigation into Cancer and Nutrition (EPIC) was established at
      IARC-WHO as a large prospective cohort study designed specifically to investigate
      the relationship of diet, nutritional factors, anthropometry and physical
      activity with cancer risk. Since the early 1990s, EPIC has made a major
      contribution to understanding the effect of these factors on population risk of
      cancer. This chapter summarises the development of the field of nutritional
      cancer epidemiology, and describes how the EPIC study was designed to investigate
      cancer and nutrition. Key findings from EPIC in the role of nutrition and
      metabolic factors and cancer are highlighted. 

PMID- 24114472
TI  - Obesity, energy balance, and cancer: a mechanistic perspective.
AB  - Nearly 36 % of adults and 20 % of children in the USA are obese, defined as a
      body mass index (BMI) >=30 kg/m(2). Obesity, which is accompanied by metabolic
      dysregulation often manifesting in the metabolic syndrome, is an established risk
      factor for many cancers. Within the growth-promoting, proinflammatory environment
      of the obese state, cross talk between macrophages, adipocytes, and epithelial
      cells occurs via obesity-associated hormones, cytokines, and other mediators that
      may enhance cancer risk and/or progression. This chapter synthesizes the evidence
      on key biological mechanisms underlying the obesity-cancer link, with particular
      emphasis on obesity-associated enhancements in growth factor signaling,
      inflammation, and vascular integrity processes, as well as obesity-dependent
      microenvironmental perturbations, including the epithelial-to-mesenchymal
      transition. These interrelated pathways represent possible mechanistic targets
      for disrupting the obesity-cancer link.

PMID- 24114473
TI  - Fruits and vegetables: updating the epidemiologic evidence for the WCRF/AICR
      lifestyle recommendations for cancer prevention.
AB  - The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR)
      current dietary recommendations for cancer prevention include "eating at least
      five portions/servings of a variety of non-starchy vegetables and or fruits every
      day". The most recent report coordinated by WCRF/AICR (2007) concluded that the
      evidence of a protective effect of fruits and vegetables on cancer was either
      "probable"-mouth, pharynx and larynx, oesophagus stomach, lung- or "limited
      suggestive"-nasopharynx, lung, colorectum, ovary, endometrium, pancreas, liver-.
      In a previous report published by WCRF/AICR in 1997, the evidence of the
      association of fruits and vegetables with cancer risk was considered convincing.
      This judgement was based mainly on the results of case-control studies. The
      association of fruit and vegetable intake and the risk of colorectal, breast and
      pancreatic cancer was re-examined in the Continuous Update Project (CUP) and the
      results were quantitatively summarised in meta-analyses. The CUP, with more data
      available, has confirmed the conclusion of the WCRF/AICR second expert report
      that there is no convincing evidence that fruits and vegetables play a role on
      cancer aetiology. On the other hand, evidence that is more consistent has been
      collected in the CUP about the role of dietary fibre and colorectal cancer. The
      evidence on the role of dietary fibre in colorectal cancer aetiology has been
      recently upgraded by the CUP expert panel from probable to convincing. 

PMID- 24114475
TI  - Mediterranean dietary pattern and chronic diseases.
AB  - The study of the relationship between the Mediterranean way of eating and the
      occurrence of diseases typical of the economically developed countries has been
      considered the starting point of nutritional epidemiology. From the Seven
      Countries Study in the 1950s to the recent European EPIC collaboration, the
      evaluation of the components of diet-affecting chronic diseases such as
      cardiovascular disease and cancer has been crucially based on the analysis of
      foods and nutrients characterizing the Mediterranean dietary habits. This long
      research history has been marked by a consistency of data over time when either
      single nutrients/food groups or more complex dietary patterns have been analyzed:
      The Mediterranean way of eating is a protective tool from cardiovascular diseases
      and many cancers. Italy has been a natural point of observation, starting from
      cardiovascular disease in the mid-1950s and continuing with major cancers. In
      spite of unfavorable lifestyle changes in the Italian population mostly due to
      globalization of unhealthy habits (richer diet and lower levels of physical
      activity), those individuals still close to the Mediterranean style are
      significantly protected. The very recent Italian data derived from the
      observation of about 50,000 individuals, participating in the Italian cohorts of
      the EPIC study, confirm these findings and are consistent with results from other
      European populations and in some cases also from North American populations.
      Moreover, several dietary trials suggest that such a way of eating improves both
      the metabolic risk condition for chronic disease and the occurrence of those
      diseases. In conclusion, a way of eating inspired by a Mediterranean dietary
      pattern is not only based on evidence but is also a palatable style that has
      contributed to protection from the epidemic of chronic diseases. 

PMID- 24114476
TI  - Dietary salt intake and risk of gastric cancer.
AB  - Humans began to use large amounts of salt for the main purpose of food
      preservation approximately 5,000 years ago and, although since then advanced
      technologies have been developed allowing drastic reduction in the use of salt
      for food storage, excess dietary salt intake remains very common. Gastric cancer
      is a common neoplasia, and dietary factors, including salt consumption, are
      considered relevant to its causation. A number of experimental studies supported
      the cocarcinogenic effect of salt through synergic action with Helicobacter
      pylori infection, in addition to some independent effects such as increase in the
      rate of cell proliferation and of endogenous mutations. Many epidemiological
      studies analyzed the relationship between excess salt intake and risk of gastric
      cancer. Both cross-sectional and prospective studies indicated a possibly dose
      dependent positive association. In particular, a comprehensive meta-analysis of
      longitudinal studies detected a strong adverse effect of total salt intake and
      salt-rich foods on the risk of gastric cancer in the general population.
      Altogether, the epidemiological, clinical, and experimental evidence supports the
      possibility of a substantial reduction in the rates of gastric cancer through
      progressive reduction in population salt intake.

PMID- 24114474
TI  - The diet as a cause of human prostate cancer.
AB  - Asymptomatic prostate inflammation and prostate cancer have reached epidemic
      proportions among men in the developed world. Animal model studies implicate
      dietary carcinogens, such as the heterocyclic amines from over-cooked meats and
      sex steroid hormones, particularly estrogens, as candidate etiologies for
      prostate cancer. Each acts by causing epithelial cell damage, triggering an
      inflammatory response that can evolve into a chronic or recurrent condition. This
      milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type
      of focal atrophy that represents the earliest of prostate cancer precursor
      lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression,
      shortened telomere segments, and epigenetic silencing of genes such as GSTP1,
      encoding the pi-class glutathione S-transferase, all characteristic of prostatic
      intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes,
      such as the gene translocations/deletions that generate fusion transcripts
      between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family
      transcription factors (such as ERG1), arise in PIN lesions and may promote
      invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate
      cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing,
      which seems to arise in response to the inflamed microenvironment generated by
      dietary carcinogens and/or estrogens as part of an epigenetic "catastrophe"
      affecting hundreds of genes, persists to drive clonal evolution through
      metastatic dissemination. The cause of the initial epigenetic "catastrophe" has
      not been determined but likely involves defective chromatin structure maintenance
      by over-exuberant DNA methylation or histone modification. With dietary
      carcinogens and estrogens driving pro-carcinogenic inflammation in the developed
      world, it is tempting to speculate that dietary components associated with
      decreased prostate cancer risk, such as intake of fruits and vegetables,
      especially tomatoes and crucifers, might act to attenuate the ravages of the
      chronic or recurrent inflammatory processes. Specifically, nutritional agents
      might prevent PIA lesions or reduce the propensity of PIA lesions to suffer
      "catastrophic" epigenome corruption. 

PMID- 24114477
TI  - Alcoholic beverages and carbonated soft drinks: consumption and gastrointestinal
      cancer risks.
AB  - Alcoholic beverages (ABs) and carbonated soft drinks (CSDs) are widely consumed
      worldwide. Given the high consumption of these beverages, the scientific
      community has increased its focus on their health impact. There is
      epidemiological evidence of a causal association between AB intake and digestive
      cancer, but the role of alcohol in determining cancer is not fully defined.
      Experimental studies have so far identified multiple mechanisms involved in
      carcinogenesis; ethanol itself is not carcinogenic but available data suggest
      that acetaldehyde (AA) and reactive oxygen species-both products of ethanol
      metabolism-have a genotoxic effect promoting carcinogenesis. Other carcinogenetic
      mechanisms include nutritional deficits, changes in DNA methylation, and impaired
      immune surveillance. As CSDs are often suspected to cause certain
      gastrointestinal disorders, consequently, some researchers have hypothesized
      their involvement in gastrointestinal cancers. Of all the ingredients, carbon
      dioxide is prevalently involved in the alteration of gastrointestinal physiology
      by a direct mucosal effect and indirect effects mediated by the mechanical
      pressure determined by gas. The role of sugar or artificial sweeteners is also
      debated as factors involved in the carcinogenic processes. However, several
      surveys have failed to show any associations between CSDs and esophageal,
      gastric, or colon cancers. On the other hand, a slight correlation between risk
      of pancreatic cancer and CSD consumption has been found. 

PMID- 24114478
TI  - Anti-inflammatory and anticancer drugs from nature.
AB  - Over the centuries, plant extracts have been used to treat various diseases.
      Until now, natural products have played an important role in anticancer therapy
      as there are more than 500 compounds from terrestrial and marine plants or
      microorganisms, which have antioxidant, antiproliferative, or antiangiogenic
      properties and are therefore able to reduce tumor growth. The recent discovery of
      new natural products has been accelerated by novel technologies (high throughput
      screening of natural products in plants, animals, marine organisms, and
      microorganisms). Vincristine, irinotecan, etoposide, and paclitaxel are examples
      of compounds derived from plants that are used in cancer treatment. Similarly,
      actinomycin D, mitomycin C, bleomycin, doxorubicin, and L-asparaginase are drugs
      derived from microorganisms. In this review, we describe the molecular mechanisms
      of natural compounds with anti-inflammatory and anticancer activities. 

PMID- 24114479
TI  - Selenium and cancer: a story that should not be forgotten-insights from genomics.
AB  - Selenium (Se) is an essential micronutrient that is incorporated into
      selenoproteins. Although epidemiological studies suggest that low Se intake is
      associated with increased risk of various cancers, the results of supplementation
      trials have been confusing. These conflicting results may be due to different
      baseline Se status and/or genetic factors. In addition, mechanistic links between
      Se intake, selenoproteins and carcinogenesis are not clear. In this article, we
      discuss the functional significance of single-nucleotide polymorphisms (SNP) in
      selenoprotein genes and the evidence as to whether or not they influence risk of
      colorectal, prostate, lung or breast cancers. Both in vitro and in vivo studies
      have shown that a small number of SNPs in genes encoding glutathione peroxidases
      1 and 4, selenoprotein P, selenoprotein S and 15-kDa selenoprotein have
      functional consequences. Data from case-control studies suggest that a variant at
      codon 198 in glutathione peroxidase 1 influences the effect of Se status on
      prostate cancer and risk, and it has also been associated with breast cancer and
      lung cancer risk, whereas variants in glutathione peroxidase 4, selenoprotein P
      and selenoprotein S may influence the risk of colorectal cancer. In addition, the
      results of gene microarray (transcriptomic) studies have identified novel
      selenoprotein biomarkers of Se status and novel downstream Se-targeted pathways.
      The work highlights the need to take baseline Se status and genetic factors into
      account in the design of future intervention trials. 

PMID- 24114480
TI  - Resveratrol: from basic studies to bedside.
AB  - Plants produce a remarkable amount of low molecular mass natural products endowed
      with a large array of pivotal biological activities. Among these molecules,
      resveratrol (3,5,4'-trihydroxystilbene) has been identified as an important
      modulator of cell phenotype with a complex and pleiotropic mode of action.
      Extensive literature regarding its activity, mainly employing cellular models,
      suggests that this polyphenol controls cell proliferation, induces
      differentiation, and activates apoptosis and autophagy. The compound also
      modulates angiogenesis and inflammation. Similarly, studies on implanted cancers
      and chemical-induced tumors confirm the potential chemotherapeutical interest of
      the compound. Likewise, several reports clearly demonstrated, in animal models,
      that the compound might positively affect the development and evolution of
      chronic diseases including type 2 diabetes, obesity, coronary heart disease,
      metabolic syndrome, and neurogenerative pathologies. Finally, a number of
      investigations stated that the toxicity of the molecule is scarce. Despite these
      promising observations, few clinical trials have yet been performed to evaluate
      the effectiveness of the molecule both in prevention and treatment of human
      chronic disease. Preliminary findings therefore suggest the need for more
      extensive clinical investigations. 

PMID- 24114481
TI  - Quercetin: a pleiotropic kinase inhibitor against cancer.
AB  - Increased consumption of fruits and vegetables can represent an easy strategy to
      significantly reduce the incidence of cancer. From this observation, derived
      mostly from epidemiological data, the new field of chemoprevention has emerged in
      the primary and secondary prevention of cancer. Chemoprevention is defined as the
      use of natural or synthetic compounds able to stop, reverse, or delay the process
      of tumorigenesis in its early stages. A large number of phytochemicals are
      potentially capable of simultaneously inhibiting and modulating several key
      factors regulating cell proliferation in cancer cells. Quercetin is a flavonoid
      possessing potential chemopreventive properties. It is a functionally pleiotropic
      molecule, possessing multiple intracellular targets, affecting different cell
      signaling processes usually altered in cancer cells, with limited toxicity on
      normal cells. Simultaneously targeting multiple pathways may help to kill
      malignant cells and slow down the onset of drug resistance. Among the different
      substrates triggered by quercetin, we have reviewed the ability of the molecule
      to inhibit protein kinases involved in deregulated cell growth in cancer cells. 

PMID- 24114482
TI  - Sulforaphane as a promising molecule for fighting cancer.
AB  - Cancer is a complex disease characterized by multiple genetic and molecular
      alterations involving transformation, deregulation of apoptosis, proliferation,
      invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors
      need host components and primary dysfunction in the tumor microenvironment, in
      addition to cell dysfunction, can be crucial for carcinogenesis. A great variety
      of phytochemicals have been shown to be potentially capable of inhibiting and
      modulating several relevant targets simultaneously and is therefore non-specific.
      Because of the enormous biological diversity of cancer, this pleiotropism might
      constitute an advantage. Phytochemicals, in particular diet-derived compounds,
      have therefore been proposed and applied in clinical trials as cancer
      chemopreventive/chemotherapeutic agents. Sulforaphane (SFN) is an isothiocyanate
      found in cruciferous vegetables. SFN has proved to be an effective
      chemoprotective agent in cell culture, in carcinogen-induced and genetic animal
      cancer models, as well as in xenograft models of cancer. It promoted potent
      cytostatic and cytotoxic effects orchestrated by the modulation of different
      molecular targets. Cell vulnerability to SFN-mediated apoptosis was subject to
      regulation by cell-cycle-dependent mechanisms but was independent of a mutated
      p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the
      cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its potential
      therapeutic benefit in clinical settings. Overall, SFN appears to be an effective
      and safe chemopreventive molecule and a promising tool to fight cancer. 

PMID- 24114483
TI  - Functions, aberrations, and advances for chromatin modulation in cancer.
AB  - Cancer initiation and progression is causally connected to genome and epigenome
      deregulations. Epigenetic deregulations (such as DNA methylation, histone
      modifications, and miRNA-based modulation) have been increasingly reported in
      tumorigenesis and different chromatin-modulating enzymes have been discovered and
      classified and their aberrations connected to cancer. A better insight into
      alterations occurring on chromatin enzymes and their impact in cancer thus
      represents a crucial step in exploiting epigenetic targeting in cancer prevention
      and treatment. 

PMID- 24114484
TI  - Epigenetics and epidemiology: models of study and examples.
AB  - Epidemiological studies have successfully identified several environmental causes
      of disease, but often these studies are limited by methodological problems (e.g.
      lack of sensitivity and specificity in exposure assessment; confounding).
      Proposed approaches to improve observational studies of environmental
      associations are Mendelian randomization and the meet-in-the-middle (MITM)
      approach. The latter uses signals from the growing field of -omics as putative
      intermediate biomarkers in the pathogenetic process that links exposure with
      disease. The first part of this approach consists in the association between
      exposure and disease. The next step consists in the study of the relationship
      between (biomarkers of) exposure and intermediate -omic biomarkers of early
      effect; thirdly, the relation between the disease outcome and intermediate -omic
      biomarkers is assessed. We propose that when an association is found in all three
      steps it is possible that there is a casual association. One of the associations
      that have been investigated extensively in the recent years but is not completely
      understood is that between environmental endocrine disruptors and breast cancer.
      Here we present an example of how the "meet-in-the-middle" approach can be used
      to address the role of endocrine disruptors, by reviewing the relevant
      literature. 

PMID- 24114486
TI  - Breast cancer and the importance of early life nutrition.
AB  - Epigenetic processes play a central role in regulating the tissue-specific
      expression of genes. Alterations in these processes can lead to profound changes
      in phenotype and have been implicated in the pathogenesis of many human diseases
      including human cancer. There is growing evidence that the environment,
      particularly variations in diet, during specific developmental periods can induce
      changes in the epigenome, which are then stably maintained throughout life
      influencing susceptibility to cancer in later life. This chapter will review the
      evidence that alterations in early life nutritional exposure can affect breast
      cancer risk through the altered epigenetic regulation of genes and discuss how
      detection of such altered epigenetic marks in early life may provide biomarkers
      to detect individuals at increased risk of disease. 

PMID- 24114485
TI  - Dietary epigenetics in cancer and aging.
AB  - Although epigenetic aberrations frequently occur in aging and cancer and form a
      core component of these conditions, perhaps the most useful aspect of epigenetic
      processes is that they are readily reversible. Unlike genetic effects that also
      play a role in cancer and aging, epigenetic aberrations can be relatively easily
      corrected. One of the most widespread approaches to the epigenetic alterations in
      cancer and aging is dietary control. This can be achieved not only through the
      quality of the diet, but also through the quantity of calories that are consumed.
      Many phytochemicals such as sulforaphane from cruciferous vegetables and green
      tea have anticancer epigenetic effects and are also efficacious for preventing or
      treating the epigenetic aberrations of other age-associated diseases besides
      cancer. Likewise, the quantity of calories that are consumed has proven to be
      advantageous in preventing cancer and extending the lifespan through control of
      epigenetic mediators. The purpose of this chapter is to review some of the most
      recent advances in the epigenetics of cancer and aging and to provide insights
      into advances being made with respect to dietary intervention into these
      biological processes that have vast health implications and high translational
      potential. 

PMID- 24114487
TI  - Olive oil and other dietary lipids in breast cancer.
AB  - Breast cancer is the most frequent malignant neoplasia among women worldwide. In
      addition to genetic and endocrine factors, the environment, and specifically
      nutritional factors, plays a key role in its aetiology. Epidemiological and in
      particular experimental studies have shown the link between dietary fat and
      breast cancer. Abundant data have attributed a potentially chemopreventive effect
      for extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean
      diet, which is associated with low incidence and mortality rates from chronic
      diseases such as breast cancer. We have demonstrated the differential modulatory
      effect of dietary lipids on mammary carcinogenesis, mainly in studies developed
      in an experimental model. Thus, diets high in n-6 polyunsaturated fatty acids
      (PUFA) have a clear stimulating influence, whereas EVOO diets mainly have a
      negative modulatory effect on breast cancer development. The specific mechanisms
      involved are not fully understood, but nowadays, it is widely accepted that they
      are numerous and complex. Our group has contributed to improving the knowledge of
      these mechanisms by demonstrating the influence of dietary lipids on the
      structure and function of cell membranes, the modulation of cell-signalling
      transduction pathways, the regulation of gene expression and growth and sexual
      maturity. 

PMID- 24114488
TI  - A holistic approach to study the effects of natural antioxidants on inflammation
      and liver cancer.
AB  - The limited effectiveness of chemotherapy and the high recurrence rate of cancers
      highlight the urgent need to identify new molecular targets and to develop new
      treatments. Numerous epidemiological studies have recently highlighted the
      existence of an inverse association between fruit and vegetable consumption,
      natural antioxidants, and cancer risk; in fact, antioxidant intake through diet
      or supplements of plant origin is strongly recommended for cancer prevention and
      cure. In general, antioxidants are substances of vegetable, mineral, or animal
      origin that neutralize free radicals and protect the body from their negative
      actions on the plasma membrane, proteins, and DNA. Hence, cancer can be prevented
      by the stimulation of the immune system to destroy cancer cells or to block their
      proliferation. Since living organisms may be studied as a whole complex system by
      the "omics sciences" which tend toward understanding and describing the global
      information of genes, mRNA, proteins, and metabolites, our aim is to use
      bioinformatics and systems biology to study cytokinome, which plays an important
      role in the evolution of inflammatory processes and is also a key component in
      the evolution of cancer, a disease recognized as depending on chronic
      inflammation and also with the concomitant presence of type 2 diabetes and
      obesity. On the whole, we define cytokinome as the totality of these proteins and
      their interactions in and around biological cells. Understanding the complex
      interaction network of cytokines in patients affected by cancers should be very
      useful both to follow the evolution of cancer from its early stages and to define
      innovative therapeutic strategies by using systems biology approaches. In this
      paper, we review some results of our group in the light of the "omics" logic, and
      in particular (1) the need for a global approach to study complex systems such as
      multifactorial cancer and, in particular, hepatocellular carcinoma, (2) the
      correlation between natural antioxidants, inflammation, and liver cancer, (3) the
      challenge and significance of the cytokinome profile, (4) the evaluation of the
      cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C
      infection, and (5) adipokine interactome. 

PMID- 24114489
TI  - Extra virgin olive oil: from composition to "molecular gastronomy".
AB  - The aim of this chapter is to provide a brief overview of the recent results of
      studies on extra virgin olive oil (EVOO) and its interactions with other food
      ingredients during cooking, to highlight basic molecular aspects of the "magic"
      of EVOO and its role in Mediterranean gastronomy. The use of raw EVOO added to
      foods after cooking (or as a salad oil) is the best way to express the original
      flavour and to maximize the intake of natural antioxidants and compounds related
      to positive effects on human health (hypotensive, anti-inflammatory, and anti
      cancerogenic, among others). EVOO, however, also exhibits its protective
      properties during/after cooking. Different chemical interactions between
      biophenolic compounds and other food ingredients (water, milk proteins,
      carotenoids of tomato, omega-3 polyunsaturated fatty acids in canned-in-oil fish
      and meat or fish proteins) occur. Even during cooking, EVOO exhibits strong
      antioxidant properties and influences the overall flavour of cooked foods. The
      physical (partitioning, emulsion) and chemical (hydrolysis, covalent binding,
      antioxidant properties) phenomena occurring during cooking of EVOO are discussed
      with emphasis on the changes in the sensory (bitterness and fruity flavour) and
      nutritional qualities of some traditional Mediterranean foods. In particular,
      tomato-oil interactions during cooking, fish canning in EVOO, meat marinated in
      EVOO before cooking and roasting and frying in EVOO are examined. The
      interactions between EVOO antioxidants and flavours with milk proteins are also
      briefly discussed. 

PMID- 24114490
TI  - Life style prevention of cancer recurrence: the yin and the yang.
AB  - There is increasing evidence that lifestyle after the diagnosis of cancer may
      affect prognosis. Several studies have shown that a Western dietary pattern,
      obesity, weight gain, a sedentary lifestyle, metabolic syndrome, high serum
      levels of insulin, growth factors, and inflammatory cytokines after the diagnosis
      of cancer are associated with an increased incidence of recurrences. Most studies
      have been on breast and colon cancer. However, in the clinical management of
      cancer, little attention is presently paid to improving lifestyle and controlling
      body weight. Lifestyle intervention trials are needed to corroborate or confute
      the observational results on cancer recurrences, but, even now, there is no
      contraindication to promoting moderate physical exercise, moderate calorie
      restriction (CR), and a Mediterranean dietary pattern. In fact, the AICR/WCRF
      2007 systematic literature review recommends cancer patients to adopt the
      lifestyle recommended for the prevention of cancer. Interestingly, the evidence
      based AICR/WCRF recommendations coincide with traditional rules, based on far
      Eastern philosophy, of avoiding extremely yin food, such as sugared beverages and
      calorie-dense foods, and extremely yang food, such as processed meat, and relying
      on the equilibrium of slightly yang food, such as whole-grain unprocessed
      cereals, eaten with slightly yin food, such as legumes and vegetables.

PMID- 24114491
TI  - New perspective for an old antidiabetic drug: metformin as anticancer agent.
AB  - Metformin, an inexpensive, well-tolerated oral agent that is commonly used in the
      first-line treatment for type 2 diabetes, has become the focus of intense
      research as a potential anticancer agent. This research reflects a convergence of
      epidemiologic, clinical, and preclinical evidence, suggesting that metformin may
      lower cancer risk in diabetics and improve outcomes of many common cancers.
      Notably, metformin mediates an approximately 30 % reduction in the lifetime risk
      of cancer in diabetic patients. There is growing recognition that metformin may
      act (1) directly on cancer cells, primarily by impacting mitochondrial
      respiration leading to the activation of the AMP-activated protein kinase (AMPK),
      which controls energy homeostasis in cells, but also through other mechanisms or
      (2) indirectly on the host metabolism, largely through AMPK-mediated reduction in
      hepatic gluconeogenesis, leading to reduced circulating insulin levels and
      decreased insulin/IGF-1 receptor-mediated activation of the PI3K pathway. Support
      for this comes from the observation that metformin inhibits cancer cell growth in
      vitro and delays the onset of tobacco carcinogen-induced lung cancer in mice and
      that metformin and its analog phenformin delay spontaneous tumor development
      cancer-prone transgenic mice. The potential for both direct antitumor effects and
      indirect host-mediated effects has sparked enormous interest, but has led to
      added challenges in translating preclinical findings to the clinical setting.
      Nonetheless, the accumulation of evidence has been sufficient to justify
      initiation of clinical trials of metformin as an anticancer agent in the clinical
      setting, including a large-scale adjuvant study in breast cancer, with additional
      studies planned.

PMID- 24114493
TI  - Inflammatory angiogenesis and the tumor microenvironment as targets for cancer
      therapy and prevention.
AB  - In addition to aberrant transformed cells, tumors are tissues that contain host
      components, including stromal cells, vascular cells (ECs) and their precursors,
      and immune cells. All these constituents interact with each other at the cellular
      and molecular levels, resulting in the production of an intricate and
      heterogeneous complex of cells and matrix defined as the tumor microenvironment.
      Several pathways involved in these interactions have been investigated both in
      pathological and physiological scenarios, and diverse molecules are currently
      targets of chemotherapeutic and preventive drugs. Many phytochemicals and their
      derivatives show the ability to inhibit tumor progression, angiogenesis, and
      metastasis, exerting effects on the tumor microenvironment. In this review, we
      will outline the principal players and mechanisms involved in the tumor
      microenvironment network and we will discuss some interesting compounds aimed at
      interrupting these interactions and blocking tumor insurgence and progression.
      The considerations provided will be crucial for the design of new preventive
      approaches to the reduction in cancer risk that need to be applied to large
      populations composed of apparently healthy individuals.

PMID- 24114494
TI  - Nutriomes and personalised nutrition for DNA damage prevention, telomere
      integrity maintenance and cancer growth control.
AB  - DNA damage at the base sequence and chromosome level is a fundamental cause of
      developmental and degenerative diseases. Multiple micronutrients and their
      interactions with the inherited and/or acquired genome determine DNA damage and
      genomic instability rates. The challenge is to identify for each individual the
      combination of micronutrients and their doses (i.e. the nutriome) that optimises
      genome stability, including telomere integrity and functionality and DNA repair.
      Using nutrient array systems with high-content analysis diagnostics of DNA
      damage, cell death and cell growth, it is possible to define, on an individual
      basis, the optimal nutriome for DNA damage prevention and cancer growth control.
      This knowledge can also be used to improve culture systems for cells used in
      therapeutics such as stem cells to ensure that they are not genetically aberrant
      when returned to the body. Furthermore, this information could be used to design
      dietary patterns that deliver the micronutrient combinations and concentrations
      required for preventing DNA damage by micronutrient deficiency or excess. Using
      this approach, new knowledge could be obtained to identify the dietary
      restrictions and/or supplementations required to control specific cancers, which
      is particularly important given that reliable validated advice is not yet
      available for those diagnosed with cancer. 

PMID- 24114492
TI  - Gut microbes, diet, and cancer.
AB  - An expanding body of evidence supports a role for gut microbes in the etiology of
      cancer. Previously, the focus was on identifying individual bacterial species
      that directly initiate or promote gastrointestinal malignancies; however, the
      capacity of gut microbes to influence systemic inflammation and other downstream
      pathways suggests that the gut microbial community may also affect risk of cancer
      in tissues outside of the gastrointestinal tract. Functional contributions of the
      gut microbiota that may influence cancer susceptibility in the broad sense
      include (1) harvesting otherwise inaccessible nutrients and/or sources of energy
      from the diet (i.e., fermentation of dietary fibers and resistant starch); (2)
      metabolism of xenobiotics, both potentially beneficial or detrimental (i.e.,
      dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial
      cells and maintenance of mucosal integrity; and (4) affecting immune system
      development and activity. Understanding the complex and dynamic interplay between
      the gut microbiome, host immune system, and dietary exposures may help elucidate
      mechanisms for carcinogenesis and guide future cancer prevention and treatment
      strategies. 

PMID- 24114495
TI  - Novel approaches in melanoma prevention and therapy.
AB  - The incidence of cutaneous melanoma has risen at a rate significantly higher than
      that for other malignancies. This increase persists despite efforts to educate
      the public about the dangers of excess exposure to UV radiation from both the sun
      and tanning beds. Melanoma affects a relatively younger population and is
      notorious for its propensity to metastasize and for its poor response to current
      therapeutic regimens. These factors make prevention an integral component to the
      goal of decreasing melanoma-related mortality. Transformation of melanocytes into
      malignant melanoma involves the interplay between genetic factors, UV exposure,
      and the tumor microenvironment. The roles of UV radiation in the etiology of
      melanoma are mediated by both direct damage of DNA through formation of
      photoproducts and production of reactive oxygen species (ROS). Many of the
      promising antioxidant agents under development for the prevention of melanoma are
      derived from foodstuffs. B-Raf is a member of the Raf kinase family of
      serine/threonine-specific protein kinases that plays a role in regulating the MAP
      kinase/ERKs signaling pathway. About 50 % of melanomas harbor activating BRAF
      mutations. BRAF mutations are found in 59 % of the melanomas arising in skin with
      intermittent sun exposure, such as trunk and arms, as compared with only 23 % of
      the acral melanomas, 11 % of mucosal melanomas, and 0 % of uveal melanomas. Two
      new agents, ipilimumab and vemurafenib, have been shown to improve outcome of
      advanced melanoma as presented at the plenary session of the 2011 annual meeting
      of the American Society of Clinical Oncology. Vemurafenib is the first
      personalized compound which demonstrated an improvement in progression-free
      survival (PFS) and overall survival (OS) in metastatic melanoma harboring the
      BRAFV600 mutation and represents the first drug of a class that exerts its anti
      proliferative activity through inhibition of a highly specific molecular target.
      GSK2118436 (dabrafenib), the second BRAF inhibitor, in phase I and II trial
      obtained similar results to vemurafenib. A phase III trial is now ongoing. Taken
      together, the early clinical development of vemurafenib and dabrafenib clearly
      confirms that BRAF inhibitors can halt or reverse disease in patients with
      melanomas carrying this mutation, improving survival times compared with
      historically standard treatments (chemotherapy and interleukin-2). The clinical
      development of other new BRAF inhibitors such as RAF265 and LGX818 is now
      ongoing. Combination strategies of BRAF inhibitors with ipilimumab, an anti-CTLA
      4 antibody, and/or MEK inhibitors or metformin are now under investigation in
      clinical trials. 

PMID- 24114496
TI  - Concluding remarks.

PMID- 24114497
TI  - Cancer incidence and mortality patterns in women with anorexia nervosa.
AB  - Caloric restriction in animals is an effective way to reduce carcinogenesis.
      Anorexia nervosa (AN) is considered a model of extreme caloric restriction in
      humans. The aim of our study was to assess cancer incidence and mortality in
      women with AN. A total of 6,009 women with at least one inpatient treatment for
      AN during the period 1973-2003 were included in the study. Standardized incidence
      ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall,
      there was no statistically significant difference in cancer incidence compared to
      women in the general population. At a statistically significant or borderline
      significant level, a higher incidence for lung cancer and cancer of lymphoid,
      hematopoietic and related tissue was observed along with a reduced breast cancer
      incidence. Women with AN had twice as high mortality from cancer in general, and
      more specifically from melanoma, cancers of genital organs and cancers of ill
      defined, secondary and unspecified sites. The increased lung cancer incidence may
      be due to smoking habits among women with AN. The worse prognosis with higher
      mortality from melanoma, cancers of genital organs and cancers of ill-defined,
      secondary and unspecified sites may be explained by AN-specific attitudes toward
      seeking medical care, adherence to treatment or worse biological precondition due
      to starvation and cachexia. 

PMID- 24114498
TI  - Increased risk of exacerbation and hospitalization in subjects with an overlap
      phenotype: COPD-asthma.
AB  - BACKGROUND: Several COPD phenotypes have been described; the COPD-asthma overlap
      is one of the most recognized. The aim of this study was to evaluate the
      prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the
      Latin American Project for the Investigation of Obstructive Lung Disease
      (PLATINO) study population, to describe their main characteristics, and to
      determine the association of the COPD-asthma overlap group with exacerbations,
      hospitalizations, limitations due to physical health, and perception of general
      health status (GHS). METHODS: The PLATINO study is a multicenter population-based
      survey carried out in five Latin American cities. Outcomes were self-reported
      exacerbations (defined by deterioration of breathing symptoms that affected usual
      daily activities or caused missed work), hospitalizations due to exacerbations,
      physical health limitations, and patients' perception of their GHS obtained by
      questionnaire. Subjects were classified in three specific groups: COPD--a
      postbronchodilator (post-BD) FEV1/FVC ratio of < 0.70; asthma--presence of
      wheezing in the last year and a minimum post-BD increase in FEV1 or FVC of 12%
      and 200 mL; and overlap COPD-asthma--the combination of the two. RESULTS: Out of
      5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD
      asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory
      symptoms, had worse lung function, used more respiratory medication, had more
      hospitalization and exacerbations, and had worse GHS. After adjusting for
      confounders, the COPD-asthma overlap was associated with higher risks for
      exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations
      (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85)
      compared with those with COPD. CONCLUSIONS: The coexisting COPD-asthma phenotype
      is possibly associated with increased disease severity.

PMID- 24114499
TI  - The impact of germline mutations on targeted therapy.
AB  - Targeted therapies provide clinical benefit and improved therapeutic index. They
      have a growing prominence in patient management and focus in drug development.
      Their development is fuelled by our deepening knowledge of complex disease
      phenotypes and the need for improvement in new therapeutic efficacy.
      Extrapolation of the biological discovery through to new therapy targeting the
      causal biological variants to drive clinical gain is challenging. Here, we review
      the impact of germline mutations on targeted therapies. Historically, germline
      changes have contributed most to our understanding of disease mechanisms, drug
      metabolism and exposure, the latter of which has enabled safer positioning of
      therapies, such as clopidogrel and irinotecan. Similarly, prescreening for
      germline variants can avoid potentially fatal hypersensitivity reactions with
      abacavir. However, germline mutations continue to emerge as a central player in
      targeting therapeutics; ivacaftor drives partial restoration of mucus secretion
      in cystic fibrosis patients harbouring specific mutations, and treatment with
      olaparib exploits germline mutations in BRCA genes to drive synthetic lethality
      as an anti-cancer mechanism. Central is definition of the causal link,
      association or contribution to the biological variance - and that we believe it
      is drugable for therapeutic gain. The demand for better therapies to treat modern
      diseases provides the appetite for continued investigation of the biological
      variance associated with germline mutations, inevitably leading to increased
      impact on the development of targeted therapeutics.

PMID- 24114501
TI  - Comparison of postmortem proteolysis between Pekin and Muscovy duck breast
      muscles.
AB  - BACKGROUND: Duck muscle is a popular source of red meat in Asia. However,
      information regarding the postmortem proteolysis of skeletal muscle between duck
      species is very limited. Therefore, the purpose of this study was to compare the
      postmortem calpain and desmin degradations between Pekin (PD) and Muscovy (MD)
      duck breast muscles stored at 5 degrees C. RESULTS: The pH and MU/m-calpain
      activity were not different (P > 0.05) between PD and MD postmortem muscles.
      However, MU-calpain activity and desmin content decreased more rapidly (P < 0.05)
      in PD than in MD samples. CONCLUSION: Therefore, our results suggest that the
      postmortem proteolysis is more rapid and extensive in breast muscle from PD
      compared to MD.

PMID- 24114502
TI  - Long-term refractive outcomes of posterior chamber phakic (spheric and toric
      implantable collamer lens) intraocular lens implantation.
AB  - To report the long-term refractive outcomes, safety, predictability, efficacy and
      complications of 349 eyes treated with posterior chamber phakic intraocular
      lenses (pIOLs). A retrospective review of consecutive clinical cases of patients
      who underwent spheric implantable collamer lens (ICL) and toric ICL (TICL)
      implantation. The study included 349 eyes of 216 patients with sphere between +8
      to -24 diopters (D) and 0 to -6.5 D of astigmatism. Statistical analysis was
      performed to identify differences between preoperative and postoperative
      refractive outcomes. Main outcome measures were preoperative and postoperative
      uncorrected distance visual acuity (UDVA), corrected distance visual acuity
      (CDVA), spherical and cylindrical errors and spherical equivalent and significant
      postoperative complications. 194 eyes were treated with TICL and 155 eyes with
      ICL. The mean age of the patients was 29 +/- 6.7 years. The mean preoperative
      sphere was -10.35 +/- 5.1 D (+8 to -24) and the postoperative sphere was -0.09 +/
      1.06 D (+3.25 to -6.5), p < 0.001. Preoperative cylinder was -2.63 +/- 1.44 (0
      to -6.5 D) and postoperative cylinder was -0.97 +/- 0.89 D (0 to -3.5), p <
      0.001. The preoperative mean spherical equivalent was -11.6 +/- 5.12 D (+7.875 to
      -25.625) and postoperative spherical equivalent was -0.52 +/- 1.03 (+2.25 to 
      6.75), p < 0.001. The mean preoperative UDVA was 1.72 +/- 0.49 and postoperative
      UDVA was 0.23 +/- 0.22, p < 0.001. The mean preoperative CDVA was 0.21 +/- 0.17
      and postoperative CDVA was 0.12 +/- 0.138, p < 0.001. The implantation of
      posterior chamber pIOLs is a safe, predictable and effective strategy to manage
      refractive errors during long-term follow-up.

PMID- 24114503
TI  - Comparison of photorefraction, autorefractometry and retinoscopy in children.
AB  - Photorefractive devices have been evaluated for their effectiveness in detecting
      anisometropia, hyperopia, myopia, and astigmatism. We investigated the
      reliability of Plusoptix S08, the newest photoscreener, and Topcon
      autorefractometer by comparing them with cycloplegic retinoscopy. Plusoptix S08,
      cycloplegic retinoscopy, and cycloplegic autorefractometer measurements for 235
      eyes of 118 children (59 female, 59 male) with a mean age of 4.9 +/- 2.6 and
      median age of 5 years (range 1-12) were conducted. The Plusoptix S08 produced the
      following mean (+/- SD) results--spherical 0.27 +/- 1.64, cylindrical power -0.81
      +/- 0.71, axis 89.73 +/- 61.18, and spherical equivalent -0.05 +/- 1.61. The
      cycloplegic retinoscopy produced the following mean (+/- SD) results--spherical
      0.12 +/- 1.35, cylindrical power -0.89 +/- 0.71, axis 92.18 +/- 68.39, and
      spherical equivalent -0.15 +/- 1.31. The cycloplegic autorefractometer produced
      the following mean (+/- SD) results--spherical 0.16 +/- 1.44, cylindrical power 
      0.88 +/- 0.72, axis 90.86 +/- 68.21, and spherical equivalent -0.12 +/- 1.41.
      This study has shown that cycloplegic autorefractometer and retinoscopy results
      are similar and Plusoptix S08 is a very safe, easy-to-use and reliable screening
      method of refraction, especially for ophthalmologists unskilled in retinoscopy.
      Plusoptix S08 is a useful tool for estimating refraction in patients for whom
      conventional autorefraction is not an option.

PMID- 24114504
TI  - Vitreous hemorrhage secondary to retinal vasculopathy in a patient with
      dyskeratosis congenita.
AB  - The aim of this study was to report a case of vitreous hemorrhage secondary to
      retinal vasculitis in a patient with dyskeratosis congenita. A 16-year-old white
      male was referred to the Ophthalmology Clinic due to deterioration of vision in
      his left eye. Medical history was significant for dyskeratosis congenita
      associated with thrombocytopenia. General physical examination revealed reticular
      pigmentation on the upper half of the chest, vertical ridges and splitting of
      finger nails, and oral mucosal leukoplakia. Ophthalmological examination of the
      anterior segment was unremarkable. Retinal examination revealed vitreous
      hemorrhage in the left eye veiling the retinal details. A possible history of
      trauma was denied. Fundus examination of the right eye showed retinal vascular
      sheathing with a few dot and blot retinal hemorrhages. Fluorescein angiography
      revealed extensive areas of non-perfusion beyond the equator in the right eye,
      later treated with scatter laser photocoagulation. We performed a 23-gauge
      vitrectomy with endolaser treatment of the new vascularization areas in the left
      eye. After 6 months, best-corrected visual acuity in the right and left eye was
      20/20 and 20/25, respectively. Rather than being confined to anterior segment
      abnormalities like conjunctivitis, blepharitis and nasolacrimal duct obstruction
      which are reported in the literature, dyskeratosis congenita can cause
      significant visual loss due to retinal vasculitis and vitreous hemorrhage.
      Therefore physicians and ophthalmologists should be aware of this possibility and
      prompt diagnosis and treatment could prevent further visual loss in such
      patients.

PMID- 24114505
TI  - Cognitive recovery and restoration of cell proliferation in the dentate gyrus in
      the 5XFAD transgenic mice model of Alzheimer's disease following 2-hydroxy-DHA
      treatment.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder in the
      elderly. In the last years, abnormalities of lipid metabolism and in particular
      of docosahexaenoic acid (DHA) have been recently linked with the development of
      the disease. According to the recent studies showing how hydroxylation of fatty
      acids enhances their biological activity, here we show that chronic treatment
      with a hydroxylated derivative of DHA, the 2-hydroxy-DHA (2OHDHA) in the 5XFAD
      transgenic mice model of AD improves performance in the radial arm maze test and
      restores cell proliferation in the dentate gyrus, with no changes in the presence
      of beta amyloid (Abeta) plaques. These results suggest that 2OHDHA induced
      restoration of cell proliferation can be regarded as a major component in memory
      recovery that is independent of Abeta load thus, setting the starting point for
      the development of a new drug for the treatment of AD. 

PMID- 24114506
TI  - "Pull and push back" concepts of longevity and life span extension.
AB  - The negative relation between metabolism and life span is a fundamental
      gerontological discovery well documented in a variety of ontogenetic and
      phylogenetic models. But how the long-lived species and populations sustain lower
      metabolic rate and, in more general terms, what is the efficient way to decline
      the metabolism? The suggested 'pull and push back' hypothesis assumes that
      decreased Po2 (hypoxia) and/or increased [Formula: see text] (hypercapnia) may
      create preconditions for the declined metabolic and aging rates. However, wider
      implementation of such ideas is compromised because of little advances in
      modification of the metabolic rate. Artificial atmosphere with controlled
      [Formula: see text] and [Formula: see text] could be a promising approach because
      of the minimal external invasions and involvement of the backward and forward
      loops ensuring physiological self-regulation of the metabolic perturbations.
      General considerations and existing data indicate that manipulations of [Formula:
      see text] may be more efficient in life span extension than [Formula: see text].
      Thus, maximum life span of mammals positively correlates with the blood [Formula:
      see text] and HCO3 (-) but not with [Formula: see text]. Yet, proportional
      decease of the body [Formula: see text] and increase of [Formula: see text] seems
      the most optimal regime ensuring lower losses of the energy equivalents.
      Furthermore, especially rewarding results could be expected when such changes are
      modeled without major external invasions using the animals' inner capacity to
      consume O2 and generate CO2, as it is typical for the extreme longevity. 

PMID- 24114507
TI  - Immunosurveillance of senescent cells: the bright side of the senescence program.
AB  - Cellular senescence, a state of irreversible cell cycle arrest, is a robust
      mechanism used to mediate tumor suppression and control the tissue damage
      response following short-term insults. In addition, the senescence associated
      secretory phenotype (SASP), one of the most profound characteristics of the
      senescence program, facilitates the immunosurveillance of senescent cells. The
      SASP includes many chemokines, cytokines and adhesion molecules that can recruit
      and activate distinct immune cells from both the innate and adaptive immune
      system such as NK cells, monocytes/macrophages and T cells. Furthermore,
      senescent cells can upregulate specific immune ligands on their cell surface that
      can mediate the recognition of these cells by specific immune cell subsets and
      lead to activation of the immune cells. Consequently, the activated immune cells
      engage explicit regulatory mechanisms to eliminate senescent cells. For example,
      recent work from our laboratory showed that perforin-granzyme exocytosis mediates
      NK-cell killing of senescent cells. Here, we summarize the current advances in
      our knowledge of the mechanisms underlying specific immune-mediated elimination
      of senescent cells. 

PMID- 24114508
TI  - Abstracts of the Convegno Monotematico SIF - Neuroimmune Pharmacology:
      Challenging Paradigms Beyond Boundaries, November 15th-16th, 2013, Varese, Italy.

PMID- 24114509
TI  - Identifying risk factors for HIV-associated neurocognitive disorders using the
      international HIV dementia scale.
AB  - HIV-associated neurocognitive disorders (HAND) persist despite great advancements
      in combination antiretroviral therapy (cART). The gold standard for diagnosing
      cognitive impairment consists of a time-consuming neuropsychological battery of
      tests given by a trained neuropsychologist, however in the outpatient HIV clinic
      this is not feasible. The International HIV Dementia Scale (IHDS) was developed
      to help identify individuals with cognitive impairment in the outpatient setting.
      The IHDS is moderately sensitive for detecting more symptomatic forms of HAND but
      sensitivity has been shown to be poor in mild impairment. The IHDS has not been
      evaluated in developed countries in large cohort populations. We conducted a
      prospective cross-sectional study of only HIV+ individuals in an urban clinic and
      evaluated the prevalence of HAND and associated risk factors for cognitive
      impairment using the IHDS. A total of 507 HIV+ individuals participated in the
      study of which the majority were male (65 %) and African American (68 %); and 41
      % had cognitive impairment. On multivariate analysis, African American race (p =
      2.21), older age (p = 1.03), high school education or less (p = 2.03) and
      depression (p = 1.05) were associated with cognitive impairment. The high
      prevalence of HAND in this group suggests that more severe forms of HAND persist
      despite cART. Identified risk factors were non-HIV-related and suggest that
      environmental and sociodemographic factors have a significant impact on cognitive
      functioning and should be given more attention. The IHDS should be further
      evaluated in large cohort HIV+ and HIV- populations in the United States, as
      there remains a significant need to identify an effective brief screening tool
      for cognitive impairment. 

PMID- 24114510
TI  - Increased response conflict in recreational cocaine polydrug users.
AB  - Recent studies suggest that recreational use of cocaine is associated with
      significant impairments in the same cognitive control functions that are affected
      by chronic use. Here we tested whether recreational cocaine use can impact the
      emergence and resolution of response conflict in conflict-inducing tasks.
      Recreational cocaine polydrug users (n = 17) and cocaine-free controls (n = 17),
      matched for sex, age, intelligence, and alcohol consumption, performed a Simon
      task-which is known to induce response conflict. Recreational users showed a
      larger Simon effect, indicating that they had more difficulty resolving stimulus
      induced response conflict. This finding is consistent with the recent literature
      showing that even small doses of cocaine are sufficient to compromise key
      cognitive control functions.

PMID- 24114511
TI  - Adaptation of visual tracking synchronization after one night of sleep
      deprivation.
AB  - The temporal delay between sensory input and motor execution is a fundamental
      constraint in interactions with the environment. Predicting the temporal course
      of a stimulus and dynamically synchronizing the required action with the stimulus
      are critical for offsetting this constraint, and this prediction-synchronization
      capacity can be tested using visual tracking of a target with predictable motion.
      Although the role of temporal prediction in visual tracking is assumed, little is
      known of how internal predictions interact with the behavioral outcome or how
      changes in the cognitive state influence such interaction. We quantified and
      compared the predictive visual tracking performance of military volunteers before
      and after one night of sleep deprivation. The moment-to-moment synchronization of
      visual tracking during sleep deprivation deteriorated with sensitivity changes
      greater than 40 %. However, increased anticipatory saccades maintained the
      overall temporal accuracy with near zero phase error. Results suggest that acute
      sleep deprivation induces instability in visuomotor prediction, but there is
      compensatory visuomotor adaptation. Detection of these visual tracking features
      may aid in the identification of insufficient sleep.

PMID- 24114512
TI  - Pathways enrichment analysis for differentially expressed genes in squamous lung
      cancer.
AB  - Squamous lung cancer (SQLC) is a common type of lung cancer, but its oncogenesis
      mechanism is not so clear. The aim of this study was to screen the potential
      pathways changed in SQLC and elucidate the mechanism of it. Published microarray
      data of GSE3268 series was downloaded from Gene Expression Omnibus (GEO).
      Significance analysis of microarrays was performed using software R, and
      differentially expressed genes (DEGs) were harvested. The functions and pathways
      of DEGs were mapped in Gene Otology and KEGG pathway database, respectively. A
      total of 2961 genes were filtered as DEGs between normal and SQLC cells. Cell
      cycle and metabolism were the mainly changed functions of SQLC cells. Meanwhile
      genes such as MCM, RFC, FEN1, and POLD may induce SQLC through DNA replication
      pathway, and genes such as PTTG1, CCNB1, CDC6, and PCNA may be involved in SQLC
      through cell cycle pathway. It is demonstrated that pathway analysis is useful in
      the identification of target genes in SQLC. 

PMID- 24114513
TI  - Guidelines for laparoscopic treatment of ventral and incisional abdominal wall
      hernias (International Endohernia Society (IEHS)-part 1.
AB  - Guidelines are increasingly determining the decision process in day-to-day
      clinical work. Guidelines describe the current best possible standard in
      diagnostics and therapy. They should be developed by an international panel of
      experts, whereby alongside individual experience, above all, the results of
      comparative studies are decisive. According to the results of high-ranking
      scientific studies published in peer-reviewed journals, statements and
      recommendations are formulated, and these are graded strictly according to the
      criteria of evidence-based medicine. Guidelines can therefore be valuable in
      helping particularly the young surgeon in his or her day-to-day work to find the
      best decision for the patient when confronted with a wide and confusing range of
      options. However, even experienced surgeons benefit because by virtue of a heavy
      workload and commitment, they often find it difficult to keep up with the ever
      increasing published literature. All guidelines require regular updating, usually
      every 3 years, in line with progress in the field. The current Guidelines focus
      on technique and perioperative management of laparoscopic ventral hernia repair
      and constitute the first comprehensive guidelines on this topic. In this issue of
      Surgical Endoscopy, the first part of the Guidelines is published including
      sections on basics, indication for surgery, perioperative management, and key
      points of technique. The next part (Part 2) of the Guidelines will address
      complications and comparisons between open and laparoscopic techniques. Part 3
      will cover mesh technology, hernia prophylaxis, technique-related issues, new
      technologic developments, lumbar and other unusual hernias, and
      training/education.

PMID- 24114514
TI  - Clinical validity of the expanded criteria for endoscopic resection of
      undifferentiated-type early gastric cancer based on long-term outcomes.
AB  - BACKGROUND: According to the Japanese Gastric Cancer Treatment Guidelines, the
      expanded criteria for endoscopic resection (ER) of undifferentiated-type early
      gastric cancer (UEGC) is ulcer-negative, intramucosal cancer 20 mm or less in
      diameter without lymphovascular invasion. The aim of this study was to confirm
      validity of the expanded criteria for curative ER of UEGC. METHODS: Subjects were
      125 patients from whom 125 UEGCs were resected endoscopically between April 1990
      and March 2011. Endoscopic mucosal resection (EMR) (28 lesions, 28 patients) or
      endoscopic submucosal dissection (ESD) (97 lesions, 97 patients) was performed.
      We determined the complete resection rate, post-ER bleeding rate, perforation
      rate, and outcome in both groups, and analyzed the survival outcomes of 84
      patients who were followed for more than 5 years (mean, 101.9 months) according
      to the indication for ER [expanded criteria for curative (n = 52) vs. criteria
      for noncurative (n = 32)]. RESULTS: Complete resection rates for EMR and ESD were
      54 % (15 of 28) and 89 % (86 of 97), respectively, with that for ESD being
      significantly higher (p < 0.01). Outcomes after ER were as follows: among 52
      cases of UEGC meeting the expanded criteria, additional surgical resection was
      performed in 11 cases of incomplete resection. No local recurrence or lymph node
      metastasis was observed. Forty-eight patients who were simply surveyed clinically
      (93.6 +/- 38.4 months) after ER survived without recurrence; the remaining 7
      patients died of other causes. Among the 32 cases of UEGC meeting the criteria
      for noncurative resection, additional surgical resection was performed in 13
      cases. Among the 19 follow-up cases (108.3 +/- 38.7 months), death due to
      metastasis of the primary disease occurred in 3 cases, death from other causes
      occurred in 5 cases, and local residual submucosal recurrence occurred in 1 case.
      CONCLUSIONS: ESD is a useful technique for complete resection as a total
      excisional biopsy compared with EMR and radical cure of UEGCs meeting the
      expanded criteria.

PMID- 24114515
TI  - Completely medial versus hybrid medial approach for laparoscopic complete
      mesocolic excision in right hemicolon cancer.
AB  - OBJECTIVE: To explore the feasibilities between operational approaches for
      laparoscopic complete mesocolic excision (CME) to right hemicolon cancer.
      METHODS: This prospective randomized controlled trial included patients admitted
      to a Shanghai minimally invasive surgical center to receive laparoscopic CME from
      September 2011 to January 2013 randomized into two groups: hybrid medial approach
      (HMA) and completely medial approach (CMA). The feasibilities and strategies of
      the two techniques were studied and compared. Furthermore, the operation time and
      vessel-related complications were designed to be the primary end points, and
      other operational findings, including the classification of the surgical plane
      and postoperative recovery, were designed to be the secondary end points for this
      study. RESULTS: After screening, 50 cases were allocated to the HMA group and 49
      to the CMA group. Within the HMA group, there were 48 cases graded with mesocolic
      plane and 2 with intramesocolic plane. For the CMA group, there were 42 cases
      graded with mesocolic plane and seven with intramesocolic plane. The differences
      between the two were insignificant, as were the number of lymph nodes retrieved.
      The mean+/-standard deviation total operation time for the CMA group was 128.3 +/
      36.4 min, which was significantly shorter than that for the HMA group, 142.6 +/-
      34.8 min. For the CMA group, the time involved in central vessel ligations and
      laparoscopic procedures was 58.5 %, 14.1 and 81.2 +/- 23.5 min, respectively,
      which were shorter than the HMA group. The vessel-related complication rate was
      significantly higher in the HMA group. CONCLUSIONS: Laparoscopic CME via the
      total medial approach is technically feasible after the precise identification of
      the surgical planes and spaces for the right hemicolon. The procedure has a
      shorter operation time and fewer vessel-related complications.

PMID- 24114516
TI  - Self-expanding metal stents or nonstent endoscopic therapy: which is better for
      anastomotic leaks after total gastrectomy?
AB  - BACKGROUND: Anastomotic leaks are a life-threatening complication of
      gastrectomies with high mortality after surgical reintervention. Endoscopic
      therapy using fibrin glue injection, endoclip, and other devices is an
      alternative to surgical intervention for anastomotic leaks. Recently, self
      expanding metal stents (SEMS) were introduced to treat anastomotic leaks. The
      purpose of this study was to assess the clinical characteristics and therapeutic
      outcomes of SEMS and nonstent endoscopic therapy (NSET) for treatment of
      anastomotic leaks after total gastrectomy with the aim of assisting endoscopists
      in choosing a treatment method. METHODS: Between July 2002 and March 2013, 13
      patients treated with SEMS and 14 patients treated with NSET for anastomotic
      leaks after total gastrectomy were enrolled onto the study. Enrolled patients
      received 16 SEMS placement sessions and 21 NSET sessions. RESULTS: No significant
      differences in baseline characteristics or clinical characteristics related to
      leakage were detected in patients with SEMS compared to NSET. The successful
      sealing rate at the first attempt by SEMS was significantly better than that of
      NSET (80.0 vs. 28.6 %, P = 0.036), whereas the successful sealing rate after
      multiple endoscopic treatments was not statistically different (80.0 vs. 64.3 %,
      P = 0.653). The main reason for reintervention with SEMS was complications and
      with NSET was nonseal (P = 0.004). Clinical outcomes including length of hospital
      stay, endoscopic treatment-related mortality, and all-cause mortality were not
      significantly different between the 2 groups. CONCLUSIONS: In terms of efficacy
      by single effort, SEMS was superior to other methods for treating anastomotic
      leaks after total gastrectomy. However, complications with SEMS should be
      considered when choosing an endoscopic treatment method.

PMID- 24114517
TI  - Optimizing working space in laparoscopy: CT measurement of the effect of pre
      stretching of the abdominal wall in a porcine model.
AB  - BACKGROUND: Determinants of working space in minimal access surgery have not been
      well studied. Using computed tomography (CT) to measure volumes and linear
      dimensions, we are studying the effect of a number of determinants of CO2 working
      space in a porcine laparoscopy model. Here we report the effects of pre
      stretching of the abdominal wall. METHODS: Earlier we had noted an increase in
      CO2 pneumoperitoneum volume at repeat insufflation with an intra-abdominal
      pressure (IAP) of 5 mmHg after previous stepwise insufflation up to an IAP of 15
      mmHg. We reviewed the data of this serendipity group; data of 16 pigs were
      available. In a new group of eight pigs, we also explored this effect at repeat
      IAPs of 10 and 15 mmHg. Volumes and linear dimensions of the CO2 pneumoperitoneum
      were measured on reconstructed CT images and compared between the initial and
      repeat insufflation runs. RESULTS: Previous stepwise insufflation of the abdomen
      with CO2 up to 15 mmHg significantly (p < 0.01) increased subsequent working
      space volume at a repeat IAP of 5 mmHg by 21 %, 7 % at a repeat IAP of 10 mmHg
      and 3 % at a repeat IAP of 15 mmHg. The external anteroposterior diameter
      significantly (p < 0.01) increased by 0.5 cm (14 %) at repeat 5 mmHg. Other
      linear dimensions showed a much smaller change. There was no statistically
      significant correlation between the duration of the insufflation run and the
      volume increase after pre-stretching at all IAP levels. CONCLUSIONS: Pre
      stretching of the abdominal wall allows for the same surgical-field exposure at
      lower IAPs, reducing the negative effects of prolonged high-pressure CO2
      pneumoperitoneum on the cardiorespiratory system and microcirculation. Pre
      stretching has important scientific consequences in studies addressing ways of
      increasing working space in that its effect may confound the possible effects of
      other interventions aimed at increasing working space.

PMID- 24114518
TI  - Prescription of antibiotics in the dental practice: a survey of dentists in
      Switzerland.
AB  - In dentistry, antibiotics are prescribed both for prophylactic and therapeutic
      purposes. Their unwarranted use, however, may lead to the selection of resistant
      microorganisms. The aim of this study was to evaluate the indications and the
      extent of antibiotic prescription by dentists in Switzerland. A questionnaire was
      sent to 800 dentists during the winter of 2008/2009. Responses to the
      questionnaire were received from 20% of them. Many respondents indicated that
      they tried to prescribe antibiotics in a selective and cautious manner.
      Nevertheless, uncertainties existed regarding the indications. For example, the
      frequency of prescribing an antibiotic when it was not absolutely necessary was
      related to the respondents' uncertainty regarding the correct diagnosis and
      therapy. Not surprisingly, two-thirds of the respondents would prefer to have
      precise guidelines for the use of these drugs.

PMID- 24114519
TI  - Association of intraprocedural blood pressure and end tidal carbon dioxide with
      outcome after acute stroke intervention.
AB  - BACKGROUND: General anesthesia (GA) for acute stroke interventions may be
      associated with inferior functional outcomes. Our goal was to identify
      physiologic parameters that mediate this association. METHODS: Consecutive
      patients treated at our institution between August 2007 and December 2010 were
      identified from a prospective database. Clinical data were then extracted by
      retrospective chart review. Variables significantly associated with outcome in
      univariate analysis were also examined in multivariate analysis, controlling for
      well-established prespecified predictors of functional outcome. RESULTS: Of the
      106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS
      and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased
      significantly after induction of GA, but there was no association between BP and
      outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were
      significantly associated with outcomes in both univariate and multivariate
      analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale
      (mRS) 0-3) was higher than in those with unfavorable outcomes (mRS 4-6): 35.2
      mmHg versus 32.2 (p = 0.03) at 60 min and 34.9 versus 31.9 (p = 0.04) at 90 min.
      The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were
      the same: 0.76 (95 % CI 0.65-0.92; p = 0.004) at 60 min and 0.76 (95 % CI 0.61
      0.93; p = 0.01) at 90 min. CONCLUSIONS: While BP decreased significantly in
      patients undergoing GA for acute stroke intervention, it did not correlate with
      patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated
      with 90-day mRS.

PMID- 24114520
TI  - Fading a concurrent activity during self-control training for children with
      autism.
AB  - We evaluated a modified technique for teaching self-control and increasing the
      duration of waiting for access to a preferred item among 3 children with autism.
      Participants initially chose an immediate small reinforcer over a delayed large
      reinforcer and a delayed large reinforcer with a concurrent activity requirement
      for the duration of the delay. When the delay to the larger reinforcer with the
      concurrent activity requirement was gradually increased from 0 s to the terminal
      delay, participants switched to and maintained selection of that option, thereby
      demonstrating increased self-control. Finally, the duration of the concurrent
      activity was gradually reduced without changing the duration of the delay to the
      large reinforcer. All 3 participants continued to select the delayed large
      reinforcer, showing self-controlled responding in the absence of a concurrent
      activity. 

PMID- 24114521
TI  - TCR-engineered T cells: a model of inducible TCR expression to dissect the
      interrelationship between two TCRs.
AB  - TCR gene modified T cells for adoptive therapy simultaneously express the Tg TCR
      and the endogenous TCR, which might lead to mispaired TCRs with harmful unknown
      specificity and to a reduced function of TCR-Tg T cells. We generated dual TCR T
      cells in two settings in which either TCR was constitutively expressed by a
      retroviral promoter while the second TCR expression was regulable by a Tet-on
      system. Constitutively expressed TCR molecules were reduced on the cell surface
      depending on the induced TCR expression leading to strongly hampered function.
      Besides that, using fluorescence resonance energy transfer we detected mispaired
      TCR dimers and different pairing behaviors of individual TCR chains with a mutual
      influence on TCR chain expression. The loss of function and mispairing could not
      be avoided by changing the TCR expression level or by introduction of an
      additional cysteine bridge. However, in polyclonal T cells, optimized TCR formats
      (cysteineization, codon optimization) enhanced correct pairing and function. We
      conclude from our data that (i) the level of mispairing depends on the individual
      TCRs and is not reduced by increasing the level of one TCR, and (ii)
      modifications (cysteineization, codon optimization) improve correct pairing but
      do not completely exclude mispairing (cysteineization). 

PMID- 24114522
TI  - Somatic copy number alterations by whole-exome sequencing implicates YWHAZ and
      PTK2 in castration-resistant prostate cancer.
AB  - Castration-resistant prostate cancer (CRPC) is the most aggressive form of
      prostate cancer (PCa) and remains a significant therapeutic challenge. The key to
      the development of novel therapeutic targets for CRPC is to decipher the
      molecular alterations underlying this lethal disease. The aim of our study was to
      identify therapeutic targets for CRPC by assessing somatic copy number
      alterations (SCNAs) by whole-exome sequencing on five CRPC/normal paired formalin
      fixed paraffin-embedded (FFPE) samples, using the SOLiD4 next-generation
      sequencing (NGS) platform. Data were validated using fluorescence in situ
      hybridization (FISH) on a PCa progression cohort. PTK2 and YWHAZ amplification,
      mRNA and protein expression were determined in selected PCa cell lines. Effects
      of PTK2 inhibition using TAE226 inhibitor and YWHAZ knock-down on cell
      proliferation and migration were tested in PC3 cells in vitro. In a larger
      validation cohort, the amplification frequency of YWHAZ was 3% in localized PCa
      and 48% in CRPC, whereas PTK2 was amplified in 1% of localized PCa and 35% in
      CRPC. YWHAZ knock-down and PTK2 inhibition significantly affected cell
      proliferation and migration in the PC3 cells. Our findings suggest that
      inhibition of YWHAZ and PTK2 could delay the progression of the disease in CRPC
      patients harbouring amplification of the latter genes. Furthermore, our validated
      whole-exome sequencing data show that FFPE tissue could be a promising
      alternative for SCNA screening using next-generation sequencing technologies.

PMID- 24114523
TI  - Nanooncology: the future of cancer diagnosis and therapy.
AB  - In recent years, there has been an unprecedented expansion in the field of
      nanomedicine with the development of new nanoparticles for the diagnosis and
      treatment of cancer. Nanoparticles have unique biological properties given their
      small size and large surface area-to-volume ratio, which allows them to bind,
      absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and
      probes with high efficiency. Their tunable size, shape, and surface
      characteristics also enable them to have high stability, high carrier capacity,
      the ability to incorporate both hydrophilic and hydrophobic substances and
      compatibility with different administration routes, thereby making them highly
      attractive in many aspects of oncology. This review article will discuss how
      nanoparticles are able to function as carriers for chemotherapeutic drugs to
      increase their therapeutic index; how they can function as therapeutic agents in
      photodynamic, gene, and thermal therapy; and how nanoparticles can be used as
      molecular imaging agents to detect and monitor cancer progression.

PMID- 24114524
TI  - Predicting survival across chronic interstitial lung disease: the ILD-GAP model.
AB  - BACKGROUND: Risk prediction is challenging in chronic interstitial lung disease
      (ILD) because of heterogeneity in disease-specific and patient-specific
      variables. Our objective was to determine whether mortality is accurately
      predicted in patients with chronic ILD using the GAP model, a clinical prediction
      model based on sex, age, and lung physiology, that was previously validated in
      patients with idiopathic pulmonary fibrosis. METHODS: Patients with idiopathic
      pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206),
      connective tissue disease-associated ILD (n=281), idiopathic nonspecific
      interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from
      an ongoing database (N=1,012). Performance of the previously validated GAP model
      was compared with novel prediction models in each ILD subtype and the combined
      cohort. Patients with follow-up pulmonary function data were used for
      longitudinal model validation. RESULTS: The GAP model had good performance in all
      ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all
      stages of disease severity and during follow-up evaluation. The GAP model had
      similar performance compared with alternative prediction models. A modified ILD
      GAP Index was developed for application across all ILD subtypes to provide
      disease-specific survival estimates using a single risk prediction model. This
      was done by adding a disease subtype variable that accounted for better adjusted
      survival in connective tissue disease-associated ILD, chronic hypersensitivity
      pneumonitis, and idiopathic nonspecific interstitial pneumonia. CONCLUSION: The
      GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model
      accurately predicts mortality in major chronic ILD subtypes and at all stages of
      disease.

PMID- 24114525
TI  - Microwave and micronization treatments affect dehulling characteristics and
      bioactive contents of dry beans (Phaseolus vulgaris L.).
AB  - BACKGROUND: Heat pretreatment is considered the first step in grain milling. This
      study therefore evaluated microwave and micronization heat treatments in
      improving the dehulling characteristics, phenolic composition and antioxidant and
      alpha-amylase activities of bean cultivars from three market classes. RESULTS:
      Heat treatments improved dehulling characteristics (hull yield, rate coefficient
      and reduced abrasive hardness index) depending on bean cultivar, whereas
      treatment effects increased with dehulling time. Micronization increased minor
      phenolic components (tartaric esters, flavonols and anthocyanins) of all beans
      but had variable effects on total phenolic content depending on market class.
      Microwave treatment increased alpha-amylase inhibitor concentration, activity and
      potency, which were strongly correlated (r2  = 0.71, P < 0.0001) with the
      flavonol content of beans. Heat treatment had variable effects on the phenolic
      composition of bean hulls obtained by abrasive dehulling without significantly
      altering the antioxidant activity of black and pinto bean hulls. Principal
      component analysis on 22 constituents analyzed in this study demonstrated the
      differences in dehulling characteristics and phenolic components of beans and
      hulls as major factors in segregating the beneficial heat treatment effects.
      CONCLUSION: Heat treatment may be useful in developing novel dietary fibers from
      beans with variable composition and bioactivity with a considerable range of
      applications as functional food ingredients.

PMID- 24114527
TI  - High prevalence of psoriatic arthritis in dermatological patients with psoriasis:
      a cross-sectional study.
AB  - The exact prevalence of psoriatic arthritis (PsA) among patients with psoriasis
      is still not conclusive. Data in the literature vary between 5.8 and 30 %.
      Objective of this study was to gain more information on the prevalence of PsA
      among patients with psoriasis in Germany. Between 09/2010 and 05/2011,
      consecutive patients from dermatological private practices and a university
      hospital with psoriasis were asked to fill out the validated German Psoriatic
      Arthritis Diagnostic (GEPARD) Questionnaire. Patients who answered >=4 questions
      with "yes" were invited to come for a rheumatological check up. Those patients
      who refused a rheumatological examination were counted as "absence of PsA".
      Laboratory tests for inflammatory markers as well as the severity of skin
      manifestations were assessed. The diagnosis of PsA was made according to the
      CASPAR criteria, and imaging was performed in addition. A total of 404
      questionnaires were evaluated; 50.5 % answered >=4 questions positively; 19.3 %
      had a history of PsA confirmed by a rheumatologist; and in 10.9 %, PsA or
      spondyloarthritis was newly diagnosed during the present study. This leads to an
      overall prevalence of PsA in patients with psoriasis of 30.2 %. The frequency of
      psoriatic arthritis in the present study is higher than expected from previous
      studies in Germany. The prevalence is consistent with findings of a large
      observational survey from Scandinavia. Using the CASPAR criteria and imaging in
      all patients, certainty of the diagnosis is very high. The GEPARD Questionnaire
      is a helpful tool to identify people at risk for psoriatic arthritis. 

PMID- 24114528
TI  - Behavioral and emotional problems on the Teacher's Report Form: a cross-national,
      cross-clinic comparative analysis of gender dysphoric children and adolescents.
AB  - For gender dysphoric children and adolescents, the school environment may be
      challenging due to peer social ostracism and rejection. To date, information on
      the psychological functioning and the quality of peer relations in gender
      dysphoric children and adolescents has been studied via parental report, peer
      sociometric methods, and social interactions in laboratory play groups. The
      present study was the first cross-national investigation that assessed behavior
      and emotional problems and the quality of peer relations, both measured by the
      Teacher's Report Form (TRF), in a sample of 728 gender dysphoric patients (554
      children, 174 adolescents), who were referred to specialized gender identity
      clinics in the Netherlands and Canada. The gender dysphoric adolescents had
      significantly more teacher-reported emotional and behavioral problems than the
      gender dysphoric children. In both countries, gender dysphoric natal boys had
      poorer peer relations and more internalizing than externalizing problems compared
      to the gender dysphoric natal girls. Furthermore, there were significant between
      clinic differences: both the children and the adolescents from Canada had more
      emotional and behavioral problems and a poorer quality of peer relations than the
      children and adolescents from the Netherlands. In conclusion, gender dysphoric
      children and adolescents showed the same pattern of emotional and behavioral
      problems in both countries. The extent of behavior and emotional problems was,
      however, higher in Canada than in the Netherlands, which appeared, in part, an
      effect of a poorer quality of peer relations. Per Bronfenbrenner's (American
      Psychologist, 32, 513-531, 1977) ecological model of human development and well
      being, we consider various interpretations of the cross-national, cross-clinic
      differences on TRF behavior problems at the level of the family, the peer group,
      and the culture at large. 

PMID- 24114530
TI  - Ethnic disparities in mental health treatment gap in a community-based survey and
      in access to care in psychiatric clinics.
AB  - BACKGROUND: Contrasting social status of ethnic groups differentially impacts the
      use of psychiatric services, including in Israel, despite its universal health
      system. However, relevant studies are limited. AIMS: To examine ethnic
      differences in mental health treatment gap and in access to specialized care.
      METHODS: Data were gathered from two sources. Study I included Mizrahi (Jews of
      North African/Asian origin, socially disadvantaged, n = 136) and Ashkenazi (Jews
      of European American origin, socially advantaged, n = 69) who were diagnosed with
      common mental disorders in the preceding 12 months in the Israeli component of
      the World Mental Health Survey. Study II included Mizrahi (n = 133) and Ashkenazi
      (n = 96) service users entering ambulatory mental health care. RESULTS: Study I
      showed that the treatment gap was larger among Mizrahi compared with Ashkenazi
      respondents (28% standard error (SE) = 4.1 and 45% SE = 6.2, respectively, sought
      services) following adjustment for sociodemographic confounders (adjusted odds
      ratio (AOR) = 2.28, 95% confidence interval (CI) = 1.1-4.8). Study II showed that
      the access to specialized care lagged over a year among 40% of service users of
      both ethnic groups. No significant ethnic differences emerged in variables
      related to delay in accessing care. CONCLUSIONS: Treatment gap was larger among
      ethnically disadvantaged compared with the advantaged group. However, once in
      treatment, service users of both ethnic groups report similar barriers to care.

PMID- 24114532
TI  - Fluorene biodegradation and identification of transformation products by white
      rot fungus Armillaria sp. F022.
AB  - A diverse surfactant, including the nonionic Tween 80 and Brij 30, the anionic
      sodium dodecyl sulphate, the cationic surfactant Tetradecyltrimethylammonium
      bromide, and biosurfactant Rhamnolipid were investigated under fluorine-enriched
      medium by Armilaria sp. F022. The cultures were performed at 25  degrees C in
      malt extract medium containing 1 % of surfactant and 5 mg/L of fluorene. The
      results showed among the tested surfactants, Tween-80 harvested the highest cell
      density and obtained the maximum specific growth rate. This due Tween-80 provide
      a suitable carbon source for fungi. Fluorane was also successfully eliminated
      (>95 %) from the cultures within 30 days in all flasks. During the experiment,
      laccase production was the highest among other enzymes and Armillaria sp. F022
      enriched culture containing Non-ionic Tween 80 showed a significant result for
      laccase activity (1,945 U/L). The increased enzyme activity was resulted by the
      increased biodegradation activity as results of the addition of suitable
      surfactants. The biotransformation of fluorene was accelerated by Tween 80 at the
      concentration level of 10 mg/L. Fluorene was initially oxidized at C-2,3
      positions resulting 9-fluorenone. Through oxidative decarboxylation, 9-fluorenone
      subjected to meta-cleavage to form salicylic acid. One metabolite detected in the
      end of experiment, was identified as catechol. Armillaria sp. F022 evidently
      posses efficient, high effective degrader and potential for further application
      on the enhanced bioremediation technologies for treating fluorene-contaminated
      soil.

PMID- 24114533
TI  - The effects of goal setting, contingent reward, and instruction on writing
      skills.
AB  - Writing is one of the primary skills that children learn in school. Interventions
      that address performance deficits and skill deficits have been shown to improve
      aspects of elementary school children's writing. This study demonstrates
      performance-based interventions (goal setting, feedback, and contingent reward)
      and a skill-based intervention (instruction) on the writing skills of a 10-year
      old child. Results indicated that the performance intervention increased the
      number of correctly spelled words, and the combination of performance and
      instructional intervention increased the number of complete sentences. 

PMID- 24114531
TI  - Obesity induced a leptin-Notch signaling axis in breast cancer.
AB  - To investigate whether obesity induces a leptin-Notch signaling axis in breast
      cancer (BC), leptin-induced Notch was determined in human MCF-7 and MDA-MB231 and
      mouse E0771 cells and in E0771-BC hosted by syngeneic lean and diet-induced
      obesity (DIO) C57BL/6J female mice. Lean and DIO mice were treated for 3 weeks
      with leptin inhibitor (PEG-LPrA2) 1 week after the inoculation of E0771 cells.
      Leptin induced Notch1, 3 and 4 in BC cells, but Notch2 expression showed opposite
      pattern in MCF-7 compared to MDA-MB231 cells. Notch loss-of-function (DAPT and
      dominant negative [R218H] RBP-Jk [CSL/CBF1]) showed that a functional leptin
      Notch signaling axis was involved in the proliferation and migration of E0771
      cells. E0771-BC onset was affected by obesity (lean mice7/10 [70%] vs. DIO mice:
      11/12 [92%]; Pearson chi(2) : p = 0.06]). PEG-LPrA2 significantly reduced BC
      growth (untreated: 19/42; [45%] vs. treated: 8/42 [19%]; Pearson chi(2) : p =
      0.008). PEG-LPrA2 did not influence the caloric intake of mice but increased
      carcass and/or body weights of lean and DIO mice inoculated with E0771 cells,
      which could be related to the improvement of health conditions (less aggressive
      disease). Importantly, BC from obese mice had higher levels of Notch3, JAG1 and
      survivin than lean mice. Inhibition of leptin signaling reduced protein levels of
      Notch (NICD1, NICD4, Notch3, JAG1 and survivin) and significantly decreased mRNA
      expression of Notch receptors, ligands and targets. PEG-LPrA's effects were more
      prominent in DIO mice. Present data suggest that leptin induces Notch, which
      could be involved in the reported higher incidence and aggressiveness and, poor
      prognosis of BC in obese patients.

PMID- 24114534
TI  - Signal normalization reduces systematic measurement differences between spectral
      domain optical coherence tomography devices.
AB  - PURPOSE: To test the effect of a novel signal normalization method for reducing
      systematic optical coherence tomography (OCT) measurement differences among
      multiple spectral-domain (SD) OCT devices. METHODS: A total of 109 eyes from 59
      subjects were scanned with two SD-OCT devices (Cirrus and RTVue) at the same
      visit. Optical coherence tomography image data were normalized to match their
      signal characteristics between the devices. To compensate signal strength
      differences, custom high dynamic range (HDR) processing was also applied only to
      images with substantially lower signal strength. Global mean peripapillary
      retinal nerve fiber layer (RNFL) thicknesses were then measured automatically
      from all images using custom segmentation software and were compared to the
      original device outputs. Structural equation models were used to analyze the
      absolute RNFL thickness difference between original device outputs and our
      software outputs after signal normalization. RESULTS: The device-measured RNFL
      thickness showed a statistically significant difference between the two devices
      (mean absolute difference 10.58 MUm, P < 0.05), while there was no significant
      difference after normalization on eyes with 62.4-MUm or thicker RNFL (mean
      absolute difference 2.95 MUm, P < 0.05). CONCLUSIONS: The signal normalization
      method successfully reduces the systematic difference in RNFL thickness
      measurements between two SD-OCT devices. Enabling direct comparison of RNFL
      thickness obtained from multiple devices would broaden the use of OCT technology
      in both clinical and research applications.

PMID- 24114536
TI  - Retinal segmentation as noninvasive technique to demonstrate hyperplasia in
      ataxia of Charlevoix-Saguenay.
AB  - PURPOSE: To present a new retinal layer segmentation technique for evaluation of
      nerve fiber hyperplasia in patients with autosomal recessive spastic ataxia of
      Charlevoix-Saguenay (ARSACS). METHODS: Five patients with a molecular diagnosis
      of ARSACS and five age- and sex-matched healthy controls underwent a full
      ophthalmologic examination, which included a new technique to segment the retinal
      layers using Spectralis optical coherence tomography (OCT). Images and data were
      correlated with diffusion tensor color-encoded magnetic resonance imaging maps,
      diffusion tensor tractographies, and retinal anatomopathologic analysis. RESULTS:
      Optical coherence tomography evaluation revealed increased thickness in the
      internal layers of the retina (inner limiting membrane, nerve fiber layer, and
      ganglion cell layer) in each patient with ARSACS compared with controls. These
      findings suggest that the presence of neurofilamentous hyperplasia in the retinas
      of patients with ARSACS correlates with the anatomopathologic findings.
      CONCLUSIONS: We found evidence of ganglion cell and nerve fiber hyperplasia in
      the retinas of ARSACS patients. The etiopathogenic mechanisms of this disease
      thus require reconsideration.

PMID- 24114535
TI  - TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3
      inflammasome activation in geographic atrophy.
AB  - PURPOSE: Accumulation of Alu RNA transcripts due to DICER1 deficiency in the
      retinal pigmented epithelium (RPE) promotes geographic atrophy. Recently we
      showed that Alu RNA activated the NLRP3 inflammasome, leading to RPE cell death
      via interleukin-18 (IL-18)-mediated MyD88 signaling. However, the molecular basis
      for NLRP3 inflammasome activation by Alu RNA is not well understood. We sought to
      decipher the key signaling events triggered by Alu RNA that lead to priming and
      activation of the NLRP3 inflammasome and, ultimately, to RPE degeneration by
      investigating the roles of the purinoreceptor P2X7, the transcription factor NF
      kappaB, and the Toll-like receptors (TLRs) in these processes. METHODS: Human and
      mouse RPE cells were transfected with a plasmid encoding an Alu element (pAlu) or
      an in vitro-transcribed Alu RNA. Inflammasome priming was assessed by measuring
      NLRP3 and IL18 mRNA levels by real-time quantitative PCR. Using immunoblotting,
      we assessed NF-kappaB activation by monitoring phosphorylation of its p65
      subunit, and inflammasome activation by monitoring caspase-1 cleavage into its
      active form. RPE degeneration was induced in mice by subretinal transfection of
      pAlu or Alu RNA. The NF-kappaB inhibitor BAY 11-7082, the P2X7 receptor
      antagonist A-740003, and the NLRP3 inflammasome inhibitor glyburide were
      delivered by intravitreous injections. We studied wild-type (WT) C57Bl/6J, P2rx7(
      /-), Nfkb1(-/-), and Tlr23479(-/-) mice. RPE degeneration was assessed by fundus
      photography and zonula occludens-1 (ZO-1) staining of mouse RPE. RESULTS: Alu RNA
      induced NF-kappaB activation, independent of TLR-1, -2, -3, -4, -6, -7, and -9
      signaling, was required for priming the NLRP3 inflammasome. Nfkb1(-/-) and P2rx7(
      /-) mice and WT mice treated with the pharmacological inhibitors of NF-kappaB,
      P2X7, or NLRP3, were protected against Alu RNA-induced RPE degeneration.
      CONCLUSIONS: NF-kappaB and P2X7 are critical signaling intermediates in Alu RNA
      induced inflammasome priming and RPE degeneration. These molecules are novel
      targets for rational drug development for geographic atrophy.

PMID- 24114537
TI  - Orphan receptor GPR179 forms macromolecular complexes with components of
      metabotropic signaling cascade in retina ON-bipolar neurons.
AB  - PURPOSE: In the mammalian retina, synaptic transmission between light-excited rod
      photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision,
      and disruption of this process leads to congenital stationary night blindness in
      human patients. The ON-bipolar neurons use the metabotropic signaling cascade,
      initiated by the mGluR6 receptor, to generate depolarizing responses to light
      induced changes in neurotransmitter glutamate release from the photoreceptor
      axonal terminals. Evidence for the identity of the components involved in
      transducing these signals is growing rapidly. Recently, the orphan receptor,
      GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been
      shown to be indispensable for the synaptic responses of ON-bipolar cells. In our
      study, we investigated the interaction of GPR179 with principle components of the
      signal transduction cascade. METHODS: We used immunoprecipitation and proximity
      ligation assays in transfected cells and native retinas to characterize the
      protein-protein interactions involving GPR179. The influence of cascade
      components on GPR179 localization was examined through immunohistochemical
      staining of the retinas from genetic mouse models. RESULTS: We demonstrated that,
      in mouse retinas, GPR179 forms physical complexes with the main components of the
      metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination
      of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic
      targeting or GPR179 expression. CONCLUSIONS: These observations suggest that the
      mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the
      interactions between the components ensure the optimal spatiotemporal
      characteristics of signal transduction.

PMID- 24114538
TI  - Upregulated stromal cell-derived factor 1 (SDF-1) expression and its interaction
      with CXCR4 contribute to the pathogenesis of severe pterygia.
AB  - PURPOSE: Stromal cell-derived factor 1 (SDF-1) and its interaction with chemokine
      receptor 4 (CXCR4) have been noted for participating in the wound healing
      process, and may paradoxically develop hypertrophic scarring. With viewing
      pterygia as a product of exaggerated wound formation, we evaluated the effects of
      SDF-1 and CXCR4 on determining the severity of pterygia. METHODS: Human pterygial
      fibroblasts were cultured from excised tissues. Then, expression levels of SDF-1
      and CXCR4 were assessed at both the mRNA and protein levels and analyzed with
      respect to the severity (grade T1 to T3) of pterygia. Expression patterns of SDF
      1 and CXCR4 in pterygium tissues were evaluated by immunohistochemistry.
      Additionally, to investigate the SDF-1-induced myofibroblast transformation of
      pterygial fibroblasts, the correlation between SDF-1 and alpha-smooth muscle
      actin (alpha-SMA) expression levels was evaluated. Furthermore, alpha-SMA levels
      in pterygial fibroblasts were determined before and after knockdown of SDF-1 and
      blockade of CXCR4 by AMD3100. RESULTS: Stromal cell-derived factor 1 and CXCR4
      were expressed in identical areas in severe pterygium tissues (grade T3) and
      CXCR4-immunopositive cells were concentrated at perivascular regions. Stromal
      cell-derived factor 1 levels in cultured pterygial fibroblasts correlated
      positively with the severity of pterygia. Stromal cell-derived factor 1 levels
      had a significant, positive correlation with alpha-SMA levels in pterygial
      fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF
      1/CXCR4 signaling in severe pterygia significantly reduced alpha-SMA levels.
      CONCLUSIONS: Stromal cell-derived factor 1 expression is upregulated in severe
      pterygia, and SDF-1 and CXCR4 interaction may contribute to the myofibroblast
      transformation, which can be possibly restored through the downregulation of the
      SDF-1/CXCR4 axis.

PMID- 24114539
TI  - Ability of different scanning protocols of spectral domain optical coherence
      tomography to diagnose preperimetric glaucoma.
AB  - PURPOSE: To evaluate the ability of the optic nerve head (ONH), retinal nerve
      fiber layer (RNFL), and ganglion cell complex (GCC) parameters of spectral domain
      optical coherence tomograph (SDOCT) in detecting preperimetric glaucoma. METHODS:
      In a cross-sectional study, 34 preperimetric glaucoma eyes (34 patients) and 72
      control eyes (72 subjects) with large physiologic optic disc cupping underwent
      ONH, RNFL, and GCC imaging with SDOCT. Preperimetric glaucoma was diagnosed in
      the presence of glaucomatous optic neuropathy on masked evaluation of optic disc
      photographs by two glaucoma experts and normal visual fields. The ability of
      SDOCT parameters to discriminate preperimetric glaucoma eyes from eyes with large
      physiologic cups was evaluated by areas under the receiver operating
      characteristic curves (AUC), sensitivities at fixed specificities, and likelihood
      ratios (LR). RESULTS: All SDOCT parameters were significantly different (P <
      0.05) between the two groups. The ONH, RNFL, and GCC parameters with best AUCs to
      differentiate preperimetric glaucoma from eyes with large physiologic cups were
      vertical cup to disc ratio (0.76), inferior quadrant RNFL thickness (0.76), and
      inferior quadrant GCC thickness (0.75), respectively. Sensitivities at 95%
      specificity of SDOCT parameters ranged between 15% and 29%. Likelihood ratios of
      outside normal limits category of parameters ranged between 3 and 11, and within
      normal limits category between 0.5 and 0.8. CONCLUSIONS: Diagnostic abilities of
      ONH, RNFL, and GCC parameters of SDOCT to differentiate preperimetric glaucoma
      eyes from control eyes with large physiologic cupping were only moderate.

PMID- 24114540
TI  - Expression and distribution of claudin subtypes in human corneal endothelium.
AB  - PURPOSE: To investigate the expression pattern of claudins in human corneal
      endothelium, and to evaluate the functional role of the claudin-10b subtype.
      METHODS: Corneal endothelium with Descemet's membrane and the corneal epithelium
      were stripped from donor human corneal stroma. Reverse transcription-polymerase
      chain reaction (RT-PCR) was performed to evaluate the claudin subtypes expressed
      in corneal endothelium, stroma, and epithelium. Immunohistochemistry was
      performed to confirm the expression of claudin subtypes in corneal endothelium,
      and the expression pattern was compared to that of corneal epithelium. Finally,
      transendothelial resistance (TER), short-circuit current (SCC), and potential
      difference (PD) were measured in human corneal endothelial cell line B4G12 cells
      with or without claudin-10 small interfering RNA (siRNA) transfection by Ussing
      chamber system. RESULTS: Transcripts for claudin-1, -2, -3, -4, -7, -10b, -11, 
      15, -22, -23, and -24 were identified in corneal endothelium sample by RT-PCR.
      Immunohistochemistry confirmed the expression of claudin-1, -2, -4, -7, -10, -11 
      15, -22, and -23 in corneal endothelium. In corneal stroma, claudin-1, -2, -3, 
      4, -5, -6, -7, -8, -10b, -11, -12, -14, -15, -22, -23, and -24 were identified by
      RT-PCR. In corneal epithelium, claudin-1, -3, -4, -7, -11, -14, and -23 were
      identified by immunohistochemistry and RT-PCR. Downregulation of claudin-10b by
      siRNA resulted in the decrease of SCC and PD, but not TER, in B4G12 cells.
      CONCLUSIONS: The expression pattern of claudin-10b(+)/claudin-14(-) was specific
      in corneal endothelium among the three corneal layers. Claudin-10b may play an
      important role in the tight junction of corneal endothelium.

PMID- 24114541
TI  - Stimulation of pontine reticular formation in monkeys with strabismus.
AB  - PURPOSE: Saccade disconjugacy in strabismus could result from any of a number of
      factors, including abnormalities of eye muscles, the plant, motoneurons, near
      response cells, or atypical tuning of neurons in saccade-related areas of the
      brain. This study was designed to investigate the possibility that saccade
      disconjugacy in strabismus is associated with abnormalities in paramedian pontine
      reticular formation (PPRF). METHODS: We applied microstimulation to 22 sites in
      PPRF and 20 sites in abducens nucleus in three rhesus macaque monkeys (one
      normal, one esotrope, and one exotrope). RESULTS: When mean velocity was compared
      between the two eyes, a slight difference was found for 1/5 sites in the normal
      animal. Significant differences were found for 5/6 sites in an esotrope and 10/11
      sites in an exotrope. For five sites in the strabismic monkeys, the directions of
      evoked movements differed by more than 40 degrees  between the two eyes. When
      stimulation was applied to abducens nucleus (20 sites), the ipsilateral eye moved
      faster for 4/6 sites in the normal animal and all nine sites in the esotrope. For
      the exotrope, however, the left eye always moved faster, even for three sites on
      the right side. For the strabismic animals, stimulation of abducens nucleus often
      caused a different eye to move faster than stimulation of PPRF. CONCLUSIONS:
      These data suggest that PPRF is organized at least partly monocularly in
      strabismus and that disconjugate saccades are at least partly a consequence of
      unbalanced saccadic commands being sent to the two eyes.

PMID- 24114542
TI  - Association between geographic atrophy progression and reticular pseudodrusen in
      eyes with dry age-related macular degeneration.
AB  - PURPOSE: To evaluate geographic atrophy (GA) progression in eyes with dry AMD and
      to determine factors related to GA expansion, notably reticular pseudodrusen
      (RPD), also known as subretinal drusenoid deposits (SDD) or reticular macular
      disease (RMD). METHODS: This was a retrospective cohort study of patients with
      dry AMD who were diagnosed with GA in at least one eye and were imaged with
      sequential fundus autofluorescence (FAF) and/or near infrared reflectance (NIR-R)
      imaging. Images were analyzed for the presence of GA within the macular region.
      Geographic atrophy progression was measured in the fields of a modified Wisconsin
      grid and spatially correlated with RPD. Factors also evaluated for association
      with GA progression included initial GA size and pattern. RESULTS: The study
      sample included 126 eyes of 92 patients, with an average follow up of 20.4 months
      (SD = 11.7). At baseline, 93.6% of eyes had RPD, and the average GA area was 2.8
      mm(2) (SD = 2.9). The average GA progression rate was 0.8 mm(2)/y (SD = 0.6),
      with a statistically significant difference between the unilobular and
      multilobular phenotype groups (0.3 mm(2)/y vs. 0.9 mm(2)/y, P = 0.02). Patients
      in the lower 50th percentile of initial GA area had a lower progression rate than
      patients in the upper 50th percentile (0.6 mm(2)/y vs. 1.1 mm(2)/y, P < 0.001).
      Geographic atrophy progression was more frequent in fields with RPD than in those
      without RPD (74.2% vs. 41.7%, P < 0.001). CONCLUSIONS: The high correlation
      between the presence of RPD (also known as SDD or RMD) and the presence of GA,
      and the expansion of GA into areas with these lesions suggest that they are an
      early manifestation of the process leading to GA.

PMID- 24114543
TI  - Functional principal component analysis reveals discriminating categories of
      retinal pigment epithelial morphology in mice.
AB  - PURPOSE: To determine whether multivariate, functional principal component
      analysis of the size and shape of retinal pigment epithelial (RPE) cell
      morphology allows discrimination of mouse RPE genotypes and age. METHODS:
      Flatmounts of RPE sheets obtained from C57BL/6J (n = 50) and rd10 (n = 61) mice
      at postnatal days 30 to 720 were stained for zonula occludens-1 (ZO-1) and imaged
      with confocal microscopy. A total of 111 flatmounts were prepared. Twenty-one
      morphometric measurements were made on tiled, composite images of complete
      flatmounts, including cell location, area, and eccentricity, using automated
      image analysis software for quantitatively measuring cell phenotypes. RESULTS: In
      young (<=61-day-old) C57BL/6J mice, the RPE morphology resembled a regular
      hexagonal array of cells of uniform size throughout the retina, except near the
      ciliary body, where the shapes of RPE resembled a soft network. Old (>=180-day
      old) C57BL/6J eyes had a subpopulation of large cells. A clear disruption of the
      regular cell size and shape appeared in rd10 mutants. Aspect ratio and cell area
      gave rise to principal components that predictively classified mouse age and
      genotype. CONCLUSIONS: Quantitative differences in the RPE sheet morphology
      allowed discrimination of rd10 from C57BL/6J strains despite the confounding
      effect of aging. This has implications for RPE sheet morphology as a potential
      early biomarker for diagnosis of eye disease and prognosis of the eye at early
      stages when disease is subtle. We conclude that an RPE cell's area and aspect
      ratio are very early quantitative indicators that predict progression to advanced
      RPE disease as manifested in rd10.

PMID- 24114544
TI  - The relationship of retinal vessel caliber with erectile dysfunction in patients
      with type 2 diabetes.
AB  - PURPOSE: To investigate the relationship of retinal vessel caliber with erectile
      dysfunction (ED) in males with type 2 diabetes. METHODS: A hospital-based cross
      sectional study. Male patients with type 2 diabetes were recruited from the
      Diabetic Management Project. All underwent a complete eye examination, a
      comprehensive interview, and blood and urine tests. Retinal vessel diameter was
      measured from retinal photographs by trained graders using semiautomated
      software. ED was defined as problems achieving or maintaining an erection and was
      assessed using a self-reported questionnaire. RESULTS: A total of 289 male
      patients with a mean (+/-SD) age of 65.3 years (+/-11.2) were assessed. After
      adjusting for age, diastolic blood pressure, duration of diabetes, HbA1c, total
      cholesterol, presence of diabetic retinopathy, and any diabetic complication,
      narrower retinal arteriolar diameter (odds ratio [OR] 1.66; 95% confidence
      interval [CI] 1.09-2.54; P = 0.019) and wider venular diameter (OR 1.58; 95% CI
      1.03-2.44; P = 0.038) were associated with ED. CONCLUSIONS: Narrower retinal
      arteriolar and wider venular diameter are independently associated with an
      increased risk of self-reported ED. These results suggest a microvascular
      component in the pathogenesis of this condition.

PMID- 24114545
TI  - Rapid and reliable assessment of the contrast sensitivity function on an iPad.
AB  - PURPOSE: Letter acuity, the predominant clinical assessment of vision, is
      relatively insensitive to slow vision loss caused by eye disease. While the
      contrast sensitivity function (CSF) has demonstrated the potential to monitor the
      slow progress of blinding eye diseases, current tests of CSF lack the reliability
      or ease-of-use to capture changes in vision timely. To improve the current state
      of home testing for vision, we have developed and validated a computerized
      adaptive test on a commercial tablet device (iPad) that provides an efficient and
      easy-to-use assessment of the CSF. METHODS: We evaluated the reliability,
      accuracy, and flexibility of tablet-based CSF assessment. Repeated tablet-based
      assessments of the spatial CSF, obtained from four normally-sighted observers,
      which each took 3 to 5 minutes, were compared to measures obtained on CRT-based
      laboratory equipment; additional tablet-based measures were obtained from six
      subjects under three different luminance conditions. RESULTS: A Bland-Altman
      analysis demonstrated that tablet-based assessment was reliable for estimating
      sensitivities at specific spatial frequencies (coefficient of repeatability 0.14
      0.40 log units). The CRT- and tablet-based results demonstrated excellent
      agreement with absolute mean sensitivity differences <0.05 log units. The tablet
      based test also reliably identified changes in contrast sensitivity due to
      different luminance conditions. CONCLUSIONS: We demonstrate that CSF assessment
      on a mobile device is indistinguishable from that obtained with specialized
      laboratory equipment. We also demonstrate better reliability than tests used
      currently for clinical trials of ophthalmic therapies, drugs, and devices.

PMID- 24114546
TI  - Retinal arterial and venous oxygen saturation is altered in diabetic patients.
AB  - PURPOSE: To determine the retinal oxygen saturation trend with onset of diabetes
      and increasing severity of diabetic retinopathy by comparing diabetic groups with
      and without retinopathy to controls. METHODS: A fundus camera-based dual
      wavelength snapshot oximeter imaged retinas of healthy subjects and patients with
      and without diabetic retinopathy. The images were analyzed to determine oxygen
      saturation in major retinal arteries and veins, which is inversely proportional
      to optical density ratio. RESULTS: Control retinal oxygen saturation (n = 14) in
      arteries was 92.3 +/- 4.2% and in veins, 57.2 +/- 6.0%. Retinal oxygen saturation
      for diabetic patients with no signs of diabetic retinopathy (NDR, n = 45) in
      arteries was 96.3 +/- 8.6% (P = 0.662) and in veins, 58.7 +/- 7.5% (P = 0.998).
      Retinal oxygen saturation for diabetics with mild to moderate nonproliferative
      diabetic retinopathy (NPDR, n = 23) in arteries was 97.7 +/- 5.8% (P = 0.590) and
      in veins, 61.1 +/- 7.6% (P = 0.658). Retinal oxygen saturation for diabetics with
      severe NPDR (n = 12) in arteries was 102 +/- 10.2% (P = 0.023) and in veins, 66.8
      +/- 8.4% (P < 0.001). Retinal oxygen saturation for patients with proliferative
      diabetic retinopathy (PDR, n = 13) in arteries was 103.6 +/- 8.7% (P = 0.003) and
      in veins, 66.6 +/- 10.2% (P = 0.026). Retinal oxygen saturation for all diabetics
      with retinopathy combined (all DR, n = 48) in arteries was 100.4 +/- 7.6% (P =
      0.004) and in veins, 64.2 +/- 8.4% (P = 0.007). CONCLUSIONS: A trend of
      increasing retinal oxygen saturation was found from controls to NDR group to
      increasing levels of diabetic retinopathy, though significance was only reached
      for the comparison of controls to severe-NPDR, PDR, and all-DR groups.

PMID- 24114547
TI  - Three-dimensional distribution of transverse collagen fibers in the anterior
      human corneal stroma.
AB  - PURPOSE: Recent investigations of human corneal structure and biomechanics have
      shown that stromal collagen fibers (lamellae) are organized into a complex,
      highly intertwined three-dimensional meshwork of transverse oriented fibers that
      increases stromal stiffness and controls corneal shape. The purpose of this study
      was to characterize the three-dimensional distribution of transverse collagen
      fibers along the major meridians of the cornea using an automated method to
      rapidly quantify the collagen fibers' angular orientation. METHODS: Three eyes
      from three donors were perfusion-fixed under pressure, excised, and cut into four
      quadrants. Quadrants were physically sectioned using a vibratome and scanned
      using nonlinear optical high-resolution macroscopy. Planes were analyzed
      numerically using software to identify collagen fiber angles relative to the
      corneal surface, stromal depth, and radial position within the anterior 250 MUm
      of the stroma. RESULTS: The range of fiber angles and the fiber percentage having
      an angular displacement greater than +/-3.5 degrees  relative to the corneal
      surface ("transverse fibers") was highest in the anterior stroma and decreased
      with depth. Numerical analysis showed no significant differences in fiber angles
      and transverse fibers between quadrants, meridians, and radial position.
      CONCLUSIONS: These results match our previous observation of a depth-dependent
      gradient in stromal collagen interconnectivity in the central cornea, and show
      that this gradient extends from the central cornea to the limbus. The lack of a
      preferred distribution of angled fibers with regard to corneal quadrant or radial
      position likely serves to evenly distribute loads and to avoid the formation of
      areas of stress concentration.

PMID- 24114548
TI  - Ameloblastoma: an aggressive lesion of the mandible.
AB  - Ameloblastoma is a benign locally invasive epithelial odontogenic tumour
      comprising 1% of all tumours and cysts arising in the jaws. It is commonly found
      in the third and fourth decade in the molar ramus region of the mandible. Among
      all types of ameloblastoma, multicystic ameloblastoma is believed to be locally
      aggressive lesion that has the tendency for recurrence. In this report we present
      a large multicystic ameloblastoma in the left body-ramus region of the mandible
      in a 55-year-old woman. This large lesion was diagnosed with the help of CT and
      was successfully managed by hemimandibulectomy with simultaneous reconstruction
      using iliac crest bone. 

PMID- 24114549
TI  - Successful treatment, despite a non-surgical approach, of severe infective
      endocarditis.
AB  - A 60-year-old man with a history of Child-Pugh class B cirrhosis was admitted to
      the hospital with 4-5 days of nausea, vomiting and altered mental status.
      Following the development of fever in the intensive care unit and methicillin
      sensitive Staphylococcus aureus bacteraemia, a large (15 mm) vegetation was
      discovered on the anterolateral papillary muscle of the mitral valve. Following a
      thorough multidisciplinary evaluation, the patient was considered to be a poor
      surgical candidate due to the significant perioperative complications associated
      with Child-Pugh class B cirrhosis. The patient was treated with 6 weeks
      intravenous nafcillin as an outpatient. Echocardiography following the treatment
      course revealed that the vegetation had completely resolved without any valvular
      dysfunction. This case report emphasises that medical management remains an
      effective alternative to surgery in complicated cases of infective endocarditis. 

PMID- 24114550
TI  - The effects of connectedness on health-promoting and health-compromising
      behaviors in adolescents: evidence from a statewide survey.
AB  - Using a social ecological perspective, we examined the effects of connectedness
      in multiple domains on health-promoting and health-compromising behaviors among
      Asian American (AA), Pacific Islander (PI), and Caucasian/White American (WA)
      adolescents in California. After adjusting for age, gender, and socioeconomic
      status, the following consistent results emerged across the three ethnic groups:
      (a) community connectedness increased the odds of physical activity; (b)
      internal, family, and school connectedness decreased, whereas friend
      connectedness increased, the odds of substance use; and (c) internal and family
      connectedness decreased the odds of violent behavior. We also found specific
      ethnic variations pertaining to the effects of connectedness. Friend
      connectedness increased the odds of violent behavior for AAs and WAs, but not for
      PIs. Meanwhile, community connectedness increased the odds of substance use and
      violent behavior for AAs and PIs, but decreased the odds of these behaviors for
      WAs. Findings for healthy dietary behavior were inconsistent across ethnic groups
      and connectedness domains. Our overall findings suggest that the effects of
      connectedness were more salient for health-compromising behaviors than for health
      promoting behaviors. Health prevention and intervention efforts in adolescents
      could target the role of their connectedness to their multiple social domains. 

PMID- 24114551
TI  - Text messaging to increase readiness to change alcohol use in college students.
AB  - We tested the feasibility and effectiveness of an alcohol counseling intervention
      delivered via personalized text messages for college students with problem
      alcohol use. College students aged 18-23 completed online substance use and
      mental health questionnaires that served as a screening tool for problem alcohol
      use. We invited students who screened positive to be randomized to intervention
      (n = 8) or control groups (n = 10) and assessed them at 1 month after they
      received their last text message. The intervention group received between four
      and six text messages daily for 4 days that required brief participant responses
      during the week following the web-based baseline assessment. Participants in the
      intervention group could also request booster texts for additional support. We
      personalized all texts, using data collected at baseline. Using a repeated
      measures ANOVA, we found that compared to the control group, the intervention
      group increased in readiness to change from baseline to follow-up (p < .01).
      Other promising trends were an increase in the intervention relative to the
      control group's confidence in their ability to change drinking behavior, and an
      increase in intentions to reduce alcohol use. These exploratory results indicate
      that the automated texting program we developed works well with college students
      and that text messaging as a means to deliver preventive interventions is a
      promising delivery platform.

PMID- 24114552
TI  - Independent associations of circulating 25-hydroxyvitamin D and parathyroid
      hormone concentrations with blood pressure among Koreans: The Korea National
      Health and Nutrition Examination Survey (KNHANES), 2009-2010.
AB  - Although lower vitamin D and higher parathyroid hormone (PTH) concentrations have
      been associated with hypertension, their independent contribution to blood
      pressure (BP) is unclear. The independent associations of serum 25-hydroxyvitamin
      D (25[OH]D) and PTH levels with BP were therefore investigated. This is a
      population-based cross-sectional study from the Korea National Health and
      Nutrition Examination Surveys, which includes a total of 4,513 participants
      (2,019 men and 2,494 women) aged >= 50 years. 25(OH)D and PTH were measured by
      radioimmunoassays, and BP was determined with a sphygmomanometer. Hypertensive
      subjects had significantly lower 25(OH)D (p = 0.023) and significantly higher PTH
      (p < 0.001) concentrations than normotensives. In subjects not taking
      antihypertensive medications, 25(OH)D showed reverse correlations with systolic
      and diastolic BP, both in men (p = 0.038-0.061 and p = 0.011-0.038, respectively)
      and in women (p = 0.006-0.018 and p = 0.001-0.011, respectively), while serum PTH
      concentrations showed positive correlations with systolic and diastolic BP in men
      (p = 0.001-0.014 and p < 0.001, respectively) and women (p < 0.001-0.008 and p =
      0.001-0.040, respectively). When 25(OH)D and PTH were included in the same model,
      both remained independently associated with BP in men and women. In conclusion,
      both lower 25(OH)D and higher PTH may be independent factors for the development
      of hypertension.

PMID- 24114555
TI  - [Amelogenesis imperfecta. Pitted hypoplastic form].

PMID- 24114554
TI  - Crosstalk between human DC subsets promotes antibacterial activity and CD8+ T
      cell stimulation in response to bacille Calmette-Guerin.
AB  - To date, little is known about the unique contributions of specialized human DC
      subsets to protection against tuberculosis (TB). Here, we focus on the role of
      human plasmacytoid (p)DCs and myeloid (m)DCs in the immune response to the TB
      vaccine bacille Calmette-Guerin (BCG). Ex vivo DC subsets from human peripheral
      blood were purified and infected with BCG expressing GFP to distinguish between
      infected and noninfected cells. BDCA-1(+) myeloid DCs were more susceptible than
      BDCA-3(+) mDCs to BCG infection. Plasmacytoid DCs have poor phagocytic activity
      but are equipped with endocytic receptors and can be activated by bystander
      stimulation. Consequently, the mutual interaction of the two DC subsets in
      response to BCG was analyzed. We found that pDCs were activated by BCG-infected
      BDCA-1(+) mDCs to upregulate maturation markers and to produce granzyme B, but
      not IFN-alpha. Reciprocally, the presence of activated pDCs enhanced
      mycobacterial growth control by infected mDCs and increased IL-1beta
      availability. The synergy between the two DC subsets promoted BCG-specific CD8(+)
      T-cell stimulation and the role of BCG-infected BDCA-1(+) mDCs could not be
      efficiently replaced by infected BDCA-3(+) mDCs in the crosstalk with pDCs. We
      conclude that mDC-pDC crosstalk should be exploited for rational design of next
      generation TB vaccines. 

PMID- 24114556
TI  - Characterization of Sulfolobus solfataricus beta-galactosidase mutant F441Y
      expressed in Pichia pastoris.
AB  - BACKGROUND: beta-Galactosidases are used to synthesize galactooligosaccharides
      (GOS). Since thermostable beta-galactosidases have the advantages of high optimal
      temperature, thermostability as well as prevention of bacterial contamination in
      the production of GOS, they have received more attention in research. In this
      study a mutant of Sulfolobus solfataricus beta-galactosidase, F441Y, was
      expressed in Pichia pastoris KM71. RESULTS: The activity of the recombinant
      enzyme reached 204.9 U mL-1 after induction by methanol in a 3 L bioreactor for
      80 h. Purification using ion exchange and hydrophobic interaction
      chromatographies resulted in a substantially pure recombinant beta-galactosidase
      that migrated with an apparent molecular weight of 56 kDa in an SDS-PAGE gel. The
      enzymatic properties were measured and the optimal pH was 5 and the optimal
      temperature was 85  degrees C. Using lactose as substrate, the K(m) and k(cat)
      values were found to be 26.3 mmol L-1 and 160.1 min-1 respectively. After
      optimizing the reaction conditions for GOS production, the yield of GOS produced
      by the recombinant enzyme at pH 6 and 75  degrees C with 700 g L-1 lactose
      solution and an enzyme quantity of 9 U mL-1 reached 61%. CONCLUSION: The F441Y of
      beta-galactosidase expressed in P. pastoris KM71 has potential application in the
      industrial preparation of GOS.

PMID- 24114557
TI  - BF-30 effectively inhibits ciprofloxacin-resistant bacteria in vitro and in a rat
      model of vaginosis.
AB  - Bacterial infections are becoming increasingly difficult to treat due to the
      increasing number of multidrug-resistant strains. Cathelicidin-BF (BF-30) is a
      cathelicidin-like antimicrobial peptide and exhibits broad antimicrobial activity
      against bacteria. In the present study, the antibacterial activity of BF-30
      against ciprofloxacin-resistant Escherichia coli and Staphylococcus aureus was
      examined, and the protective effects of this peptide against these bacteria in
      rats with bacterial vaginosis were identified for the first time. The data showed
      that BF-30 had effective antimicrobial activities against ciprofloxacin-resistant
      E. coli and S. aureus. The minimal inhibitory concentrations for both bacterial
      strains were 16 MUg/ml, and the minimal bactericidal concentrations were 64 and
      128 MUg/ml, respectively. A time course experiment showed that the CFU counts
      rapidly decreased after BF-30 treatment, and the bacteria were nearly eliminated
      within 4 h. BF-30 could reduce the fold change (CFU/ml) in local colonization by
      drug-resistant E. coli and S. aureus to 0.01 at a dose of 0.8 mg/kg/day in the
      rats' vaginal secretions. In addition, BF-30 induced membrane permeabilization
      and bound to the genomic DNA, interrupting protein synthesis. Taken together, our
      data demonstrate that BF-30 has potential therapeutic value for the prevention
      and treatment of bacterial vaginosis.

PMID- 24114558
TI  - Application of 13C-labeling and 13C-13C COSY NMR experiments in the structure
      determination of a microbial natural product.
AB  - The elucidation of the structures of complex natural products bearing many
      quaternary carbons remains challenging, even in this advanced spectroscopic era.
      (13)C-(13)C COSY NMR spectroscopy shows direct couplings between (13)C and (13)C,
      which comprise the backbone of a natural product. Thus, this type of experiment
      is particularly useful for natural products bearing consecutive quaternary
      carbons. However, the low sensitivity of (13)C-based NMR experiments, due to the
      low natural abundance of the (13)C nucleus, is problematic when applying these
      techniques. Our efforts in the (13)C labeling of a microbial natural product,
      cyclopiazonic acid (1), by feeding (13)C-labeled glucose to the fungal culture,
      enabled us to acquire (13)C-(13)C COSY NMR spectra on a milligram scale that
      clearly show the carbon backbone of the compound. This is the first application
      of (13)C-(13)C COSY NMR experiments for a natural product. The results suggest
      that (13)C-(13)C COSY NMR spectroscopy can be routinely used for the structure
      determination of microbial natural products by (13)C-enrichment of a compound
      with (13)C-glucose. 

PMID- 24114559
TI  - Fabrication and in vitro biological evaluation of photopolymerisable
      hydroxyapatite hydrogel composites for bone regeneration.
AB  - The aim of this study was to improve the bioactive and compressive properties of
      photopolymerisable polyethylene glycol hydrogels with the incorporation of
      hydroxyapatite at different loadings. The synthesis of pure hydroxyapatite was
      verified through Fourier transform infrared spectroscopy (FTIR) analysis by the
      complete reaction of all constituents. The formation of a bioactive layer of the
      hydrogel based composites was confirmed through the formation of carbonate
      hydroxyapatite after soaking the samples in simulated body fluid. The
      incorporation of hydroxyapatite into the system resulted in an increase in
      Young's modulus from 4.36 to 12.73 MPa and an increase in the stress at limit
      value from 1.20 to 4.42 MPa. This was due to the hydroxyapatite absorbing the
      compressive load, the polymer matrix distributing the load, a reduction in
      swelling and the presence of physical crosslinking between both components. Drug
      dissolution testing showed that the release rate of a drug from the hydrogels was
      dependent on the molecular weight of the polymer and the type of drug used.

PMID- 24114560
TI  - Geographical distribution of publications in the scientific field of surgical
      oncology.

PMID- 24114561
TI  - [Reticular drusen over time with SD-OCT].
AB  - AIM: The aim of the study was the analysis of reticular drusen (RDR) in patients
      with age-related macular degeneration using simultaneous confocal scanning laser
      ophthalmoscopy (cSLO) and spectral domain optical coherence tomography (SD-OCT)
      at different time points. METHODS: Included in this retrospective analysis were
      47 eyes from 32 patients (median age 80.1 years, range 66-89 years) with RDR at
      baseline and at least one follow-up visit. Registration of the cSLO near-infrared
      reflectance image and the SD-OCT B-scan (Spectralis HRA + OCT, Heidelberg
      Engineering, Heidelberg) at different time points was carried out using the
      AutoRescan tool. RESULTS: While either no alterations or increase in the RDR area
      (n=19 eyes) or RDR density (n=15) were seen by cSLO imaging, the analysis of the
      SD-OCT B-scans at different time points revealed a more complex picture. An
      increase in two well visible lesions at the baseline visit was detected in 8 eyes
      at the first follow-up and in 3 eyes at the second follow-up examination. A
      regression was seen in 5 eyes at the first follow-up and in 3 eyes at the second
      follow-up visit. In most eyes (n=23), an increase of one with a parallel decrease
      of the second RDR lesion in the identical B-scan was identified at the first
      follow-up visit, whereas individual RDR showed an increase at the second follow
      up examination that had initially shown a decrease in size at the first follow-up
      visit. CONCLUSIONS: The results indicate underlying dynamic processes in the
      development and changes of RDR over time. For a more accurate analysis, the exact
      registration of SD-OCT B-scans at different time points and the use of high
      resolution very dense volume scans would be helpful in order to assess such
      discrete changes of miniscule intraretinal lesions over time.

PMID- 24114562
TI  - Association between clean indoor air laws and voluntary smokefree rules in homes
      and cars.
AB  - OBJECTIVES: This study examines the influence that smokefree workplaces,
      restaurants and bars have on the adoption of smokefree rules in homes and cars,
      and whether there is an association with adopting smokefree rules in homes and
      cars. METHODS: Bivariate probit models were used to jointly estimate the
      likelihood of living in a smokefree home and having a smokefree car as a function
      of law coverage and other variables. Household data were obtained from the
      nationally representative Social Climate Survey of Tobacco Control 2001, 2002 and
      2004-2009; clean indoor air law data were from the American Nonsmokers' Rights
      Foundation Tobacco Control Laws Database. RESULTS: 'Full coverage' and 'partial
      coverage' smokefree legislation is associated with an increased likelihood of
      having voluntary home and car smokefree rules compared with 'no coverage'. The
      association between 'full coverage' and smokefree rule in homes and cars is 5%
      and 4%, respectively, and the association between 'partial coverage' and
      smokefree rules in homes and cars is 3% and 4%, respectively. There is a positive
      association between the adoption of smokefree rules in homes and cars.
      CONCLUSIONS: Clean indoor air laws provide the additional benefit of encouraging
      voluntary adoption of smokefree rules in homes and cars.

PMID- 24114563
TI  - Tax, price and cigarette brand preferences: a longitudinal study of adult smokers
      from the ITC Mexico Survey.
AB  - BACKGROUND: Recent tax increases in Mexico differed in structure and provided an
      opportunity to better understand tobacco industry pricing strategies, as well as
      smokers' responses to any resulting price changes. OBJECTIVES: To assess if taxes
      were passed onto consumers of different cigarette brands, the extent of brand
      switching and predictors of preference for cheaper national brands. METHODS:
      Using data from three waves of the Mexican administration of the International
      Tobacco Control Survey, we analysed self-reported brand and price paid at last
      cigarette purchase. Generalised estimating equations were used to determine
      predictors of price and preference for national brands. RESULTS: The average
      price of premium/international brands increased each year from 2008 to 2011;
      however, the price for discount/national brands increased only from 2010 to 2011.
      The percentage of smokers who smoked national brands remained stable between 2008
      and 2010 but dropped in 2011. Factors related to smoking national brands as
      opposed to international brands included being male and having relatively older
      age, lower education, lower income and higher consumption. CONCLUSIONS: Tobacco
      industry pricing strategies in the wake of ad valorem taxes implemented in Mexico
      prior to 2011 had the impact of segmenting the market into discount national
      brands and premium international brands. The specific tax increase implemented in
      2011 reduced the price gap between these two segments by raising the price of the
      national brands relative to the international brands. Evidence for trading up was
      found after the 2011 tax increase. These results provide further evidence for the
      relevance of tax policy as a tobacco control strategy; in particular, they
      illustrate the importance of how specific rather than ad valorem taxes can reduce
      the potential for downward brand switching in the face of decreasing cigarette
      affordability.

PMID- 24114564
TI  - Human rights and ethical considerations for a tobacco-free generation.
AB  - In recent years, a new tobacco 'endgame' has been proposed: the denial of tobacco
      sale to any citizen born after a certain year, thus creating new tobacco-free
      generations. The proposal would not directly affect current smokers, but would
      impose a restriction on potential future generations of smokers. This paper
      examines some key legal and ethical issues raised by this proposal, critically
      assessing how an obligation to protect human rights might limit or support a
      state's ability to phase out tobacco. 

PMID- 24114565
TI  - Molecular markers for variation in spawning date in a hatchery population of
      rainbow trout (Oncorhynchus mykiss).
AB  - We examined the distribution of alleles at 63 microsatellite loci distributed
      across 29 linkage groups in broodstock females from a commercial population of
      rainbow trout spawning on different dates throughout the season (August to
      January). A total of 368 females, 184 and 117 females from each of the tail-ends
      of the spawning distribution and a subsample of 67 females spawning in the
      middle, were used to detect marker-trait associations. Twenty-one loci in a
      subset of genomic regions (RT-5, 7, 8, 10, 12, 14, 15, 22, 23, 24, 25, 29, 30,
      and 31) were significantly associated with variation in spawning date. Many of
      these markers localize to regions with known spawning date quantitative trait
      loci based on previous studies. An individual assignment analysis was used to
      test how well the molecular data could be used to assign individuals to their
      correct spawning group, and markers were given a ranking reflecting their
      contribution to the accuracy of assignment. The top 15 ranked markers were
      successful at assigning the majority of females to the correct spawning group
      based on genotype with an average accuracy of 76 %. The most likely genes that
      could contribute to these differences in spawning date are discussed. Together,
      these data indicate that the loci could be incorporated into a selection index
      with phenotype data to increase the accuracy of selection for spawning date. 

PMID- 24114566
TI  - A case of fatal cetuximab-induced interstitial lung disease during the first
      weeks of treatment.
AB  - Cetuximab is a monoclonal antibody targeting the epidermal growth factor
      receptor. It has demonstrated activity against a number of cancers including
      lung, head and neck, and colorectal. The most common side effects associated with
      this agent are dermatological; however, other types of toxicities have been
      reported with varying frequencies. Here, we report a case of interstitial lung
      disease that developed within the first 4 weeks of cetuximab treatment initiation
      in a patient with metastatic colorectal cancer and led to patient death. Early
      fatal pulmonary events secondary to cetuximab is rarely reported in the
      literature; this case report highlights the importance of awareness among
      treating health care professionals of this potentially fatal toxicity.

PMID- 24114567
TI  - Effects of white noise on off-task behavior and academic responding for children
      with ADHD.
AB  - We evaluated the effects of white noise played through headphones on off-task
      behavior, percentage of items completed, and percentage of items completed
      correctly for 3 students with attention deficit hyperactivity disorder (ADHD).
      Headphones plus white noise were associated with decreases in off-task behavior
      relative to baseline and headphones-only (no white noise) control conditions.
      Little change in academic responding occurred across conditions for all
      participants. 

PMID- 24114568
TI  - Breast cancer statistics, 2013.
AB  - In this article, the American Cancer Society provides an overview of female
      breast cancer statistics in the United States, including data on incidence,
      mortality, survival, and screening. Approximately 232,340 new cases of invasive
      breast cancer and 39,620 breast cancer deaths are expected to occur among US
      women in 2013. One in 8 women in the United States will develop breast cancer in
      her lifetime. Breast cancer incidence rates increased slightly among African
      American women; decreased among Hispanic women; and were stable among whites,
      Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006
      to 2010. Historically, white women have had the highest breast cancer incidence
      rates among women aged 40 years and older; however, incidence rates are
      converging among white and African American women, particularly among women aged
      50 years to 59 years. Incidence rates increased for estrogen receptor-positive
      breast cancers in the youngest white women, Hispanic women aged 60 years to 69
      years, and all but the oldest African American women. In contrast, estrogen
      receptor-negative breast cancers declined among most age and racial/ethnic
      groups. These divergent trends may reflect etiologic heterogeneity and the
      differing effects of some factors, such as obesity and parity, on risk by tumor
      subtype. Since 1990, breast cancer death rates have dropped by 34% and this
      decrease was evident in all racial/ethnic groups except American Indians/Alaska
      Natives. Nevertheless, survival disparities persist by race/ethnicity, with
      African American women having the poorest breast cancer survival of any
      racial/ethnic group. Continued progress in the control of breast cancer will
      require sustained and increased efforts to provide high-quality screening,
      diagnosis, and treatment to all segments of the population.

PMID- 24114570
TI  - Cranberry-derived proanthocyanidins prevent formation of Candida albicans
      biofilms in artificial urine through biofilm- and adherence-specific mechanisms.
AB  - OBJECTIVES: Candida albicans is a common cause of nosocomial urinary tract
      infections (UTIs) and is responsible for increased morbidity and healthcare
      costs. Moreover, the US Centers for Medicare & Medicaid Services no longer
      reimburse for hospital-acquired catheter-associated UTIs. Thus, development of
      specific approaches for the prevention of Candida urinary infections is needed.
      Cranberry juice-derived proanthocyanidins (PACs) have efficacy in the prevention
      of bacterial UTIs, partially due to anti-adherence properties, but there are
      limited data on their use for the prevention and/or treatment of Candida UTIs.
      Therefore, we sought to systematically assess the in vitro effect of cranberry
      derived PACs on C. albicans biofilm formation in artificial urine. METHODS: C.
      albicans biofilms in artificial urine were coincubated with cranberry PACs at
      serially increasing concentrations and biofilm metabolic activity was assessed
      using the XTT assay in static microplate and silicone disc models. RESULTS:
      Cranberry PAC concentrations of >=16 mg/L significantly reduced biofilm formation
      in all C. albicans strains tested, with a paradoxical effect observed at high
      concentrations in two clinical isolates. Further, cranberry PACs were additive in
      combination with traditional antifungals. Cranberry PACs reduced C. albicans
      adherence to both polystyrene and silicone. Supplementation of the medium with
      iron reduced the efficacy of cranberry PACs against biofilms. CONCLUSIONS: These
      findings indicate that cranberry PACs have excellent in vitro activity against C.
      albicans biofilm formation in artificial urine. We present preliminary evidence
      that cranberry PAC activity against C. albicans biofilm formation is due to anti
      adherence properties and/or iron chelation.

PMID- 24114571
TI  - The timing of activity is a regulatory signal during development of neural
      connections.
AB  - In PNS and CNS remarkable rearrangements occur soon after the connections are
      laid down in the course of embryonic life. These processes clearly follow the
      period of developmental cell death and mostly take place during the very
      beginning of postnatal life. They consist in changes of the peripheral fields of
      neurons, marked by elimination of many inputs, while others undergo further
      maturation and strengthening. Along the efforts to uncover the signals that
      regulate development, it turned out that while the initial construction of the
      circuits is heavily based on chemical cues, the subsequent rearrangement is
      markedly influence by activity. Here we describe experiments testing the
      influence on developmental plasticity of a particular aspect of activity, the
      timing of nerve impulses in the competing inputs. Two recent investigations are
      reviewed, indicating strikingly similar developmental features in quite different
      systems, neuromuscular and visual. A sharp contrast between the effects of
      synchrony and asynchrony emerges, indicating that Hebb-related activity rules are
      important not only for learning but also for development. 

PMID- 24114573
TI  - Is office-based myringoplasty a suitable alternative to surgical tympanoplasty?

PMID- 24114572
TI  - Kruppel-like factor 8 ameliorates Alzheimer's disease by activating beta-catenin.
AB  - A sustained loss of Wnt signaling function may be involved in the pathology of
      Alzheimer's disease (AD). Kruppel-like factor 8 (KLF8) induces the activation of
      Wnt/beta-catenin signaling pathway. Thus, KLF8 may be related with the risk of
      AD. We want to know the role of KLF8 in the development of AD. A rat brain slice
      model for AD was established. Quantitative RT-PCR, western blotting, and
      fluorescence staining assays were carried out to examine the effects of KLF8 on
      the protein expression of some important molecules, which are associated with the
      development of AD. The enhanced expression level of KLF8 could increase the
      protein expression level of beta-catenin, which interacted with and inhibited
      nuclear factor-kappa B (NF-kappaB). The protein levels of KLF8 and beta-catenin
      were increased, while the level of NF-kappaB was decreased in the AD model. The
      inhibition of NF-kappaB was followed by the decrease of the protein expression
      levels of amyloid precursor protein (APP) and phosphorylated tau (Phospho-Tau).
      The protein level of KLF8 was decreasing from stages I to IV in patients with AD.
      This study provides evidence that KLF8 can inhibit the progression of AD.

PMID- 24114574
TI  - Multi-modality imaging in the assessment of a metastatic cardiac rhabdomyosarcoma
      presenting with recurrent ventricular tachycardia.

PMID- 24114575
TI  - Visualization of pericarditis by fluorodeoxyglucose PET.

PMID- 24114576
TI  - Reversible restenosis after transcatheter aortic valve implantation.

PMID- 24114577
TI  - Multimodality imaging of coronary artery dissection and cardiac contusion after
      blunt chest trauma.

PMID- 24114578
TI  - Giant pulmonary mass complicating pulmonary homograft replacement.

PMID- 24114579
TI  - Reference intervals of serum cystatin C/creatinine ratio of 30 postnatal days in
      neonates.
AB  - BACKGROUND: A number of recent reports have suggested that the cystatin
      C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in
      pediatric patients. In this study we investigated the reference intervals of the
      serum CysC/Cr ratio for neonates including very low birth weight infants. CASE
      DIAGNOSIS/TREATMENT: A total of 883 blood samples were collected from 246
      neonates during the first 30 days of life for the concurrent measurement of serum
      CysC and Cr levels. Infants with symptoms or signs of acute kidney injury,
      systemic illness, congenital anomaly, or renal pathology were excluded. The
      association between serum CysC/Cr ratio and the subgroups of patients was also
      analyzed. Reference intervals of serum CysC/Cr ratio were determined according to
      the postnatal age and post-conceptional age (PCA). CysC/Cr ratio level increased
      according to PCA, except in the first three postnatal days. The serum CysC/Cr
      ratio correlated positively with gestational age at birth, birth weight,
      postnatal age, and PCA, and negatively with serum CysC and Cr (P < 0.001).
      CONCLUSIONS: Reference levels of serum CysC/Cr ratio were determined according to
      postnatal age and PCA. As the serum CysC/Cr ratio is dependent on several
      clinical parameters, these should be considered when assessing the serum CysC/Cr
      ratio in neonates.

PMID- 24114580
TI  - Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD):
      kidney-related and non-kidney-related phenotypes.
AB  - Autosomal recessive polycystic kidney disease (ARPKD), although less frequent
      than the dominant form, is a common, inherited ciliopathy of childhood that is
      caused by mutations in the PKHD1-gene on chromosome 6. The characteristic
      dilatation of the renal collecting ducts starts in utero and can present at any
      stage from infancy to adulthood. Renal insufficiency may already begin in utero
      and may lead to early abortion or oligohydramnios and lung hypoplasia in the
      newborn. However, there are also affected children who have no evidence of renal
      dysfunction in utero and who are born with normal renal function. Up to 30 % of
      patients die in the perinatal period, and those surviving the neonatal period
      reach end stage renal disease (ESRD) in infancy, early childhood or adolescence.
      In contrast, some affected patients have been diagnosed as adults with renal
      function ranging from normal to moderate renal insufficiency to ESRD. The
      clinical spectrum of ARPKD is broader than previously recognized. While bilateral
      renal enlargement with microcystic dilatation is the predominant clinical
      feature, arterial hypertension, intrahepatic biliary dysgenesis remain important
      manifestations that affect approximately 45 % of infants. All patients with ARPKD
      develop clinical findings of congenital hepatic fibrosis (CHF); however, non
      obstructive dilation of the intrahepatic bile ducts in the liver (Caroli's
      disease) is seen at the histological level in only a subset of patients.
      Cholangitis and variceal bleeding, sequelae of portal hypertension, are life
      threatening complications that may occur more often in advanced cases of liver
      disease. In this review we focus on common and uncommon kidney-related and non
      kidney-related phenotypes. Clinical management of ARPKD patients should include
      consideration of potential problems related to these manifestations.

PMID- 24114581
TI  - Indications and outcomes of endoscopic CO2 laser cricopharyngeal myotomy.
AB  - OBJECTIVES/HYPOTHESIS: To describe indications, management, and outcomes of
      endoscopic CO2 laser cricopharyngeal myotomy (CPM). STUDY DESIGN: Case series
      with chart review. METHODS: All patients treated with endoscopic CO2 laser CPM
      over a 6-year period were identified. A retrospective chart review was performed
      for surgical indication, history and physical examinations, and swallow
      evaluations. Swallowing outcomes were assessed using the Functional Outcome
      Swallowing Scale (FOSS); findings were compared across groups. RESULTS: Eighty
      seven patients underwent endoscopic CO2 laser CPM during the study period for
      cricopharyngeal dysfunction. Indications included Zenker's diverticulum (ZD)
      (39), DiGeorge syndrome (two), stroke (five), nerve injury (two), radiation for
      head and neck cancer (15), idiopathic (16), hyperfunctional tracheoesophageal
      speech (five) and dysphagia from cricopharyngeus stricture after laryngectomy
      (three). Mean, median, and mode time to feeding postoperatively were 1.4, 1, and
      0 days respectively. Mean, median, and mode hospital stays were 1.8, 1, and 1 day
      respectively. Overall, FOSS scores improved from 2.6 to 1.6 (P < .001).
      Improvement was greatest for patients with ZD (2.4 to 1.0) and cricopharyngeal
      dysfunction from nerve injury (3.3 to 1.8) and least for those with prior
      radiation (3.9 to 3.2). All patients undergoing CPM for poor tracheoesophageal
      speech regained speech postoperatively. No patients developed mediastinitis,
      abscess, or fistula. CONCLUSIONS: Endoscopic CO2 laser CPM is a safe treatment
      for cricopharyngeal dysfunction of various causes, though swallowing outcomes may
      vary depending on the surgical indication. Early feeding postoperatively after
      CPM is safe and facilitates early hospital discharge. LEVEL OF EVIDENCE: 4.

PMID- 24114582
TI  - The reciprocal relationship of ASD, ADHD, depressive symptoms and stress in
      parents of children with ASD and/or ADHD.
AB  - This study investigated the role of parental Autism spectrum disorder (ASD),
      attention-deficit/hyperactivity disorder (ADHD), and depressive symptoms on
      parenting stress in 174 families with children with ASD and/or ADHD, using
      generalized linear models and structural equation models. Fathers and mothers
      reported more stress when parenting with their child with ASD and/or ADHD than
      when parenting with the unaffected sibling; they also experienced more stress
      than a norm population. Depressive symptoms were most pronounced in the parents
      of children with ASD and ASD+ADHD. Spouse correlations were found for ASD,
      depression, and parenting stress. Paternal ASD and maternal ADHD symptoms were
      related to increased parenting stress, and parental ADHD symptoms with depressive
      symptoms and parenting stress. The results highlight the increased burden of
      raising a child with ASD and/or ADHD and the reciprocal relationship this has
      with parents' ASD, ADHD, and depressive symptoms, and levels of stress. 

PMID- 24114584
TI  - Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial
      epithelial cells at a low concentration of aflatoxin B1.
AB  - Cytochrome P450 2A13 (CYP2A13), mainly expressed in human respiratory tract, is
      highly efficient in the metabolic activation of aflatoxin (AF) B1 (AFB1) and is
      assumed to play a role in human lung tumorigenesis in airborne AFB1 exposure. To
      validate the assumption, we exposed human bronchial epithelial (BEAS-2B) cells
      stably expressing CYP2A13 (B-2A13), CYP1A2 (B-1A2) and CYP2A6 (B-2A6) to 0.1-10
      nM AFB1 for 30-50 passages. B-2A13 cells showed increased sensitivity to 0.1 nM
      AFB1-induced neoplastic transformation and the formation of tumors in nude mice
      were observed at passage 30 (P30) while it occurred at P50 B-1A2 cells. B-2A6,
      similar to vector control, showed no neoplastic transformation in this condition.
      Additionally, AFB1-DNA adducts and 8-OHdG significantly increased in transformed
      P40 B-2A13, in parallel with the upregulation of p-ATR, p-BRCA1, Mre11, Rad50 and
      Rad51. However, the apoptosis of P40 cells was near normal, while the expression
      of Bax, C-Caspase 3 and C-PARP increased passage-dependently. Inhibition of ATR
      (ATR siRNA or NU6027) reversely increased the apoptosis of P40 B-2A13 cells in
      parallel with the upregulation of Bax, C-Caspase 3 and C-PARP, suggesting that
      ATR plays an important role in maintaining cell survival via antiapoptosis.
      Additionally, activation of ATR was necessary to neoplastic transformation since
      blockage of ATR in P40 cells inhibited DNA damage repair response and anchorage
      independent growth. Our data demonstrated that CYP2A13 played a critical role in
      AFB1-induced neoplastic transformation. ATR-mediated the dysfunction of apoptosis
      and DNA damage repair might be involved. These results help establish a linkage
      between airborne AFB1 and human respiratory carcinoma. 

PMID- 24114583
TI  - The evolving genomic classification of lung cancer.
AB  - EGFR gene mutations and ALK gene fusions are well-characterized molecular targets
      in NSCLC. Activating alterations in a variety of potential oncogenic driver genes
      have also been identified in NSCLC, including ROS1, RET, MET, HER2, and BRAF.
      Together with EGFR and ALK, these mutations account for ~20% of NSCLCs. The
      identification of these oncogenic drivers has led to the design of rationally
      targeted therapies that have produced superior clinical outcomes in tumours
      harbouring these mutations. Many patients, however, have de novo or acquired
      resistance to these therapies. In addition, most NSCLCs are genetically complex
      tumours harbouring multiple potential activating events. For these patients,
      disease subsets are likely to be defined by combination strategies involving a
      number of targeted agents. These targets include FGFR1, PTEN, MET, MEK, PD-1/PD
      L1, and NaPi2b. In light of the myriad new biomarkers and targeted agents,
      multiplex testing strategies will be invaluable in identifying the appropriate
      patients for each therapy and enabling targeted agents to be channelled to the
      patients most likely to gain benefit. The challenge now is how best to interpret
      the results of these genomic tests, in the context of other clinical data, to
      optimize treatment choices in NSCLC.

PMID- 24114585
TI  - Long-term effects of exposure to disease-modifying drugs in the offspring of
      mothers with multiple sclerosis: a retrospective chart review.
AB  - INTRODUCTION: Multiple sclerosis (MS) mainly affects women of fertile age. To
      date, the only recommendation for women with MS intending to become pregnant is
      to stop all treatment. This recommendation reflects the concerns about the
      effects of disease-modifying drugs (DMDs) on the offspring. The objective of the
      present study was to assess the potential long-term effects of maternal exposure
      to DMDs on the offspring. METHOD: This was a retrospective study revising medical
      data on the offspring of women with MS. These women now have children aged at
      least 1 year and include a group of patients that were not exposed to any DMDs
      for at least 3 months prior to pregnancy and during the whole gestation (control
      group). Another group of patients had at least 2 weeks of exposure to DMDs,
      mainly to interferon beta or glatiramer acetate RESULTS: The women with MS
      participating in this study have children currently aged, on average, 6.6 years
      (range 1-39 years). There was no pattern of drug-related adverse events or
      complications in the children whose mothers were exposed to DMDs. No specific
      long-term adverse events were observed in the offspring of women with MS who were
      exposed to drugs during pregnancy. The profile of relevant diagnoses in their
      children was similar to that of children whose mothers had not been exposed to
      DMDs. CONCLUSIONS: The present retrospective study did not show a specific
      profile of long-term deleterious drug effects on children born from mothers who
      were exposed to drugs for MS treatment.

PMID- 24114586
TI  - Second generation antipsychotic-induced type 2 diabetes: a role for the
      muscarinic M3 receptor.
AB  - Second generation antipsychotics (SGAs) are widely prescribed to treat various
      disorders, most notably schizophrenia and bipolar disorder; however, SGAs can
      cause abnormal glucose metabolism that can lead to insulin-resistance and type 2
      diabetes mellitus side-effects by largely unknown mechanisms. This review
      explores the potential candidature of the acetylcholine (ACh) muscarinic M3
      receptor (M3R) as a prime mechanistic and possible therapeutic target of interest
      in SGA-induced insulin dysregulation. Studies have identified that SGA binding
      affinity to the M3R is a predictor of diabetes risk; indeed, olanzapine and
      clozapine, SGAs with the highest clinical incidence of diabetes side-effects, are
      potent M3R antagonists. Pancreatic M3Rs regulate the glucose-stimulated
      cholinergic pathway of insulin secretion; their activation on beta-cells
      stimulates insulin secretion, while M3R blockade decreases insulin secretion.
      Genetic modification of M3Rs causes robust alterations in insulin levels and
      glucose tolerance in mice. Olanzapine alters M3R density in discrete nuclei of
      the hypothalamus and caudal brainstem, regions that regulate glucose homeostasis
      and insulin secretion through vagal innervation of the pancreas. Furthermore,
      studies have demonstrated a dynamic sensitivity of hypothalamic and brainstem
      M3Rs to altered glucometabolic status of the body. Therefore, the M3R is in a
      prime position to influence glucose homeostasis through direct effects on
      pancreatic beta-cells and by potentially altering signalling in the hypothalamus
      and brainstem. SGA-induced insulin dysregulation may be partly due to blockade of
      central and peripheral M3Rs, causing an initial disruption to insulin secretion
      and glucose homeostasis that can progressively lead to insulin resistance and
      diabetes during chronic treatment. 

PMID- 24114589
TI  - Emerging scholar best article award, 2013.

PMID- 24114588
TI  - Contextual socioeconomic status and mental health counseling use among US
      adolescents with depression.
AB  - Most adolescents with depressive disorders do not receive any mental health
      services, even though effective treatments exist. Although research has examined
      numerous individual-level factors associated with mental health service use among
      depressed adolescents, less is known about the role of contextual factors. This
      study examines the relationship between contextual-level socioeconomic status
      (SES) and clinic-based mental health counseling use among US adolescents with
      high depressive symptoms in urban and suburban areas. Data from the first two
      waves of the National Longitudinal Study of Adolescent Health (N = 1,133; 59 %
      female) were analyzed using multilevel logistic models in which adolescents were
      nested within counties. After controlling for individual-level predisposing,
      enabling, and need characteristics, as well as county racial/ethnic composition,
      county SES was positively associated with clinic-based counseling use among
      depressed youth. A one standard deviation increase in the county affluence index
      was associated with 43 % greater odds of receiving any clinical counseling
      services. Furthermore, the positive relationship between county affluence and
      clinical counseling use was no longer significant after controlling for the
      county supply of mental health specialist physicians. The results indicate that
      county residential context is a key correlate of mental health service use among
      depressed adolescents, such that those who live in lower SES counties with fewer
      mental health specialists are less likely to receive treatment. 

PMID- 24114587
TI  - Novel delivery systems for nicotine replacement therapy as an aid to smoking
      cessation and for harm reduction: rationale, and evidence for advantages over
      existing systems.
AB  - Nicotine replacement therapy (NRT) has been used in the treatment of tobacco
      dependence for over three decades. Whilst the choice of NRT was limited early on,
      in the last ten years there has been substantial increase in the number of
      nicotine delivery devices that have become available. This article briefly
      summarises existing forms of NRT, evidence of their efficacy and use, and reviews
      the rationale for the development of novel products delivering nicotine via
      buccal, transdermal or pulmonary routes (including nicotine mouth spray, nicotine
      films, advanced nicotine inhalers and electronic cigarettes). It presents
      available evidence on the efficacy, tolerability and abuse potential of these
      products, with a focus on their advantages as well as disadvantages compared with
      established forms of NRT for use as an aid to both smoking cessation as well as
      harm reduction. 

PMID- 24114590
TI  - Attachment security to mothers and fathers and the developmental trajectories of
      depressive symptoms in adolescence: which parent for which trajectory?
AB  - This longitudinal study investigated the links between adolescents' perceptions
      of attachment security in their relationships with their mothers and fathers and
      developmental trajectories of depressive symptoms in a community sample of 414
      adolescents (45 % males). The participants were followed annually from age 11
      (end of elementary school) to 16 (end of high school). Group-based trajectory
      modeling analyses conditional on risk and protective factors identified four
      trajectories of depressive symptoms across adolescence: moderate stable (MS;
      54.57 % of the sample), low stable (LS; 27.16 %), moderate increasing (MI; 11.30
      %), and high declining (HD; 6.97 %). Membership in the HD versus LS trajectory
      group was predicted by attachment security to both the mother and father at
      baseline (age 11), whereas attachment security to the mother increased the odds
      of belonging to the MS and MI groups. These relationships were statistically
      significant after controlling for gender, anxiety symptoms, and academic
      competence. The findings are discussed with respect to their contribution to
      attachment theory and the research on the complementary contributions of mothers
      and fathers to the prevention of depressive symptomatology during adolescence.

PMID- 24114591
TI  - Extranodal natural killer/T-Cell lymphoma: A population-based comparison of
      sinonasal and extranasal disease.
AB  - OBJECTIVES/HYPOTHESIS: Extranodal natural killer/T-cell Lymphoma (ENKTL) is a
      rare, aggressive malignancy that preferentially affects the paranasal region.
      This study analyzes the demographic, clinicopathologic, incidence, and survival
      characteristics of sinonasal ENKTL (SN-ENKTL) and extranasal ENKTL (EN-ENKTL) in
      a comparative fashion. STUDY DESIGN: Retrospective analysis. METHODS: The
      Surveillance, Epidemiology, and End Results database was queried; 528 cases were
      available for frequency and incidence analysis, and 473 for survival analysis.
      Data were examined according to age, gender, race, histology, the presence of
      systemic (or B) symptoms, treatment, and Ann Arbor stage. RESULTS: Extranasal
      disease was a poor prognostic factor (hazard ratio [HR] = 1.69, 95% confidence
      interval [CI] = 1.30-2.19, P < .05). Patients with EN-ENKTL were older (mean 53.8
      vs. 49.9 years, P < .05), most were male (72.5% vs. 59.8%, P < .05), and they
      were more likely to present with stage IIIE/IV disease (38.33% vs. 18.26%, P <
      .05). B symptoms were present in 38.41% of the EN-ENKTL group (vs. 22.86%, P <
      .05), and were a poor prognostic factor in this group only (HR = 1.6593, 95% CI =
      1.05-2.62, P < .05). Radiation therapy demonstrated a survival advantage among
      both groups, especially in early stage disease. CONCLUSIONS: SN-ENKTL carries a
      significantly better prognosis than EN-ENKTL, which presents at more advanced
      stages. Radiation therapy was associated with increased survival in both groups,
      especially in cases of localized disease. LEVEL OF EVIDENCE: 2b.

PMID- 24114593
TI  - The vestibulo-ocular reflex and subjective balance after vestibular schwannoma
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the vestibulo-ocular reflex and its
      relationship with subjective balance in a long-term follow-up after vestibular
      schwannoma surgery. STUDY DESIGN: Retrospective cohorts study in a tertiary
      referral hospital. Forty-nine consecutive patients on which vestibular schwannoma
      surgery was performed at least 1 year before. METHODS: Patients are classified in
      accordance with the morphology of the vestibulo-ocular reflex (VOR) into two
      groups: Group A, in which covert and overt saccades always occur in an organized
      fashion; and group B, in which covert and overt saccades randomly occur during
      head impulse and once finished. We evaluate the presence of covert and overt
      saccades and the morphology of the VOR measured by the video head impulse test
      (vHIT) and its relationship with subjective balance measured by Dizziness
      Handicap Inventory (DHI). RESULTS: The group B patients returned a higher score
      in total DHI and all three subscales without any predominant subscale (P =
      0,0002; t test). Group B patients were older than those in group A (P = 0,024; t
      test). No differences were found in sex distribution, tumor size, or side or time
      interval after surgery. Regarding the unaffected side, overt saccades were found
      to be more frequent in group B patients (P = 0.05; X(2)). CONCLUSIONS: Long-term
      follow-up after vestibular schwannoma surgery has shown that 22% of the patients
      display a particular abnormality in the VOR because refixation saccades occur in
      a random fashion after elicitation of the reflex in the HIT test. These patients
      report the higher level of vestibular disability and handicap. LEVEL OF EVIDENCE:
      2b.

PMID- 24114592
TI  - Structural and compositional changes in erythrocyte membrane of obese compared to
      normal-weight adolescents.
AB  - Unhealthy dietary habits are key determinants of obesity in adolescents. Assuming
      that dietary fat profile influences membrane lipid composition, the aim of this
      study was to analyze structural changes in the erythrocyte membrane of obese
      compared to normal-weight adolescents. The study was conducted in a group of 11
      obese and 11 normal-weight adolescent subjects. The lipid profile, lipid
      peroxidation and acetylcholinesterase enzyme (AChE) activity were analyzed by
      conventional methods. The structural properties of reconstituted erythrocyte
      membrane were characterized by X-ray diffraction. Erythrocyte membrane from obese
      adolescents had a lipid profile characterized by a higher
      cholesterol/phospholipid ratio, an increase in saturated fatty acid and a
      decrease in monounsaturated and n-6 polyunsaturated fatty acid concentrations.
      Differences in lipid content were associated with changes in the structural
      properties of reconstituted membranes and the oxidative damage of erythrocyte
      membrane. The lower oxidative level shown in the obese group (0.15 +/- 0.04 vs.
      0.20 +/- 0.06 nmol/mg for conjugated diene concentrations and 2.43 +/- 0.25 vs.
      2.83 +/- 0.31 nmol/mg protein for malondialdehyde levels) was related to a lower
      unsaturation index. These changes in membrane structural properties were
      accompanied by a lower AChE activity (1.64 +/- 0.13 vs. 1.91 +/- 0.24 nmol
      AChE/[min mg protein]) in the obese group. The consequences of unhealthy dietary
      habits in adolescents are reflected in the membrane structural properties and may
      influence membrane-associated protein activities and functions. 

PMID- 24114594
TI  - Human plasma cells express granzyme B.
AB  - While studying the plasma cell (PC) compartment in human tonsils, we identified
      that immunoglobulin kappa or lambda chain-expressing PCs are the main cells
      expressing granzyme B (GrzB). In vitro studies revealed that activated B cells
      differentiated into GrzB-expressing PCs when co-cultured with macrophages and
      follicular helper T cells. This effect could be reproduced on combined
      stimulation of IL-15 (produced by macrophages) and IL-21 (produced by T
      follicular helper cells) in a STAT3-dependent manner. Whereas IL-21 triggers the
      transcription of mRNA of GrzB, IL-15 synergizes the translation of GrzB proteins.
      The precise role of GrzB in PC biology remains to be understood and studies in
      mice will not help as their PCs do not express GrzB. 

PMID- 24114595
TI  - Thioglucose-bound gold nanoparticles increase the radiosensitivity of a triple
      negative breast cancer cell line (MDA-MB-231).
AB  - BACKGROUND: Gold nanoparticles (GNPs) have been conceived to cause increased
      cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by
      cells may induce increased radiation effects. Here we report the
      radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes
      (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays.
      METHODS: Transmission electron microscopy (TEM) was used to observe the
      distribution of Glu-GNPs in cells. Inductively coupled plasma atomic emission
      spectroscopy (ICP-AES) was used to measure the quantities of Glu-GNPs absorbed by
      cells. After treatment of Glu-GNPs with a series of concentrations, we used the
      MTT and clonogenic assays to confirm the radiation enhancement effect of Glu-GNPs
      on MDA-MB-231 cells. The cell cycle distribution was analyzed by flow cytometry
      to further explore the mechanisms of enhanced radiosensitivity of Glu-GNPs.
      RESULTS: TEM showed that Glu-GNPs are mainly distributed in the cytoplasm of
      cells, including endosomes and lysosomes. ICP-AES indicates that MDA-MB-231 cells
      absorb more 49-nm Glu-GNPs than 16-nm Glu-GNPs in number (P < 0.05). Glu-GNPs
      have little cytotoxicity toward MDA-MB-231 cells with a concentration below 20
      nM. In the clonogenic assay, the combination of Glu-GNPs with radiation induced a
      significant growth inhibition, compared with radiation alone (P < 0.05). Moreover
      49-nm Glu-GNPs induced much greater radiation effects than 16-nm Glu-GNPs (P <
      0.05). Flow cytometry shows that Glu-GNPs can help radiation arrest more cells in
      the G2/M phase, with greater effect with 49-nm Glu-GNPs than 16-nm Glu-GNPs.
      CONCLUSIONS: Glu-GNPs can increase the cytotoxicity of radiation toward MDA-MB
      231 cells, probably by regulating the distribution of the cell cycle, with more
      cells in the G2/M phase. The effect of radiation enhancement may be related to
      the quantities of Glu-GNPs in the cells.

PMID- 24114596
TI  - [Facial pain- a rare cause. Impacted lower third molars causing primarily
      "unclear" facial pain: a case report].
AB  - Orofacial pain often causes special difficulties to patients and dentists.
      Numerous differential diagnoses require the utilization of a coordinated
      diagnostic concept. Often, multiple causes lead to the need for a complex
      treatment plan. Impacted third molars are a potential cause of a variety of
      complications. Caries, pulp necrosis, and periapical infection are some of the
      infrequent causes of such pain. The presented case shows just such a
      constellation, resulting in primarily "unclear" orofacial pain. A diagnostic
      sequence generally leads to the correct diagnosis and thereby allows for fast and
      effective therapy. This shows how important structured diagnostics are,
      especially in cases of "unclear" pain. 

PMID- 24114598
TI  - Subcutaneous emphysema of the abdominal wall.

PMID- 24114597
TI  - Influence of casein hydrolysates on exopolysaccharide synthesis by Streptococcus
      thermophilus and Lactobacillus delbrueckii ssp. bulgaricus.
AB  - BACKGROUND: A lot of interesting research has been undertaken to enhance the
      yield of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB). The
      objective of this study was to determine the influence of casein hydrolysates
      (CH) with molecular weight less than 3 kDa on cell viability, EPS synthesis and
      the enzyme activity involved in EPS synthesis during the co-culturing of
      Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus in MRS
      broth for 72 h at 37 +/- 0.1  degrees C. RESULTS: The highest EPS yield (150.1 mg
      L-1) was obtained on CH prepared with papain (CHP) at 48 h. At 24 h, EPS were
      composed of galactose, glucose and rhamnose in a molar ratio of 1.0:2.4:1.5. The
      monosaccharide composition changed with extension of the fermentation time. The
      activities of alpha-phosphoglucomutase, uridine 5'-diphosphate (UDP)-glucose
      pyrophosphorylase and UDP-galactose 4-epimerase were associated with EPS
      synthesis. Moreover, the activities of beta-phosphoglucomutase and deoxythymadine
      5'-diphosphate (dTDP)-glucose pyrophosphorylase involved in rhamnose synthesis
      were very low at the exponential growth phase and could not be detected during
      other given periods. CONCLUSION: The influence of different CH (<3 kDa) on LAB
      viability, EPS production, EPS monomeric composition and activity levels of key
      metabolic enzymes was distinct. Besides, their influence was related to the
      distribution of amino acids.

PMID- 24114599
TI  - Peripheral T-cell lymphoma in a patient with Crohn's disease.
AB  - A 46-year-old man with a long-standing history of Crohn's disease who was treated
      with multiple therapies over a period of 9 years presented with oral lesions
      which on biopsy demonstrated peripheral T-cell lymphoma. Initially, the
      development of T-cell lymphoma was presumed to be secondary to prolonged
      immunosuppression but it did not respond to withholding immunosuppressive
      therapy. On treatment with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin
      and prednisone) chemotherapy, complete remission was achieved. Although
      development of malignancies in the immune-suppressed patient with Crohn's disease
      has been previously described but we present a rare case of T-cell lymphoma in a
      similar patient, which has not been reported before. 

PMID- 24114600
TI  - Concurrent granulomatous hepatitis, pneumonitis and sepsis as a complication of
      intravesical BCG immunotherapy.
AB  - Intravesical administration of BCG is a relatively simple procedure used
      successfully in the treatment of superficial transitional cell carcinoma of the
      urinary bladder. It is usually well tolerated with few major side effects. The
      authors report the case of an 80-year-old man who presented with sepsis,
      jaundice, hepatic and pulmonary failure 10 days after his last BCG instillation
      therapy, that was attributed to concurrent granulomatous hepatitis and
      pneumonitis due to Mycobacterium bovis dissemination. In rare instances severe
      life-threatening complications occur in relation with BCG instillation
      immunotherapy that may involve multiple organs and have different presentations
      and require a high index of suspicion and clinical awareness in a wide range of
      medical specialties. 

PMID- 24114601
TI  - Disseminated fusariosis with immune reconstitution syndrome and cracking mycotic
      aortic aneurysm in a 55-year-old patient with acute myeloid leukaemia.

PMID- 24114602
TI  - Itchy lesions in pigmented skin.
AB  - A 37-year-old woman with type VI skin presented with 1-year history of pruritic
      lesions affecting her arms, chest and legs. The lesions were approximately 5 mm
      in diameter, annular and with a raised border. A skin biopsy was performed which
      showed a diagnosis of disseminated superficial actinic porokeratosis.
      Porokeratosis is an unusual presentation in pigmented skin and there are very
      limited reports of this occurrence in the literature. 

PMID- 24114603
TI  - Management of ST elevation myocardial infarction in pregnancy.
AB  - A 33-year-old lady in the second trimester of pregnancy presented to the
      emergency department having suffered a cardiac arrest at home. An emergency
      caesarean section was performed in the resuscitation area. On return of
      spontaneous circulation, a 12-lead ECG showed anterior ST elevation myocardial
      infarction. She was transferred to our tertiary centre for an emergency coronary
      angiography and was successfully treated, making a full recovery. This case
      report examines the relatively rare entity of myocardial infarction in pregnancy
      and looks at the mechanisms underlying this. 

PMID- 24114604
TI  - A large abdominal wall abscess as a presentation of gallstone disease in an
      elderly woman.

PMID- 24114605
TI  - Atypical vitamin B6 deficiency: a rare cause of unexplained neonatal and
      infantile epilepsies.
AB  - ALDH7A1 and PNPO deficiencies are rare inborn errors of vitamin B6 metabolism
      causing perinatal seizure disorders. The phenotypic variability, however, is
      broad. To assess the frequency of these deficiencies in unexplained infantile
      epilepsy, we screened 113 patients for mutations in both genes. We identified 1
      patient with an epilepsy phenotype resembling Dravet syndrome and likely
      pathogenic mutations in ALDH7A1. Presenting features were highly atypical of
      pyridoxine-dependent epilepsy, including febrile seizures, response to
      anticonvulsive drugs, and periods of seizure freedom without pyridoxine
      treatment. "Hidden" vitamin B6 deficiencies might be rare but treatable causes of
      unexplained epilepsy extending beyond the classical phenotypes. 

PMID- 24114606
TI  - Long-term follow-up in infantile-onset lambert-eaton myasthenic syndrome.
AB  - Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder
      characterized by proximal limb muscle weakness, fatigability, decreased deep
      tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton
      myasthenic syndrome: one most frequently associated with small-cell lung cancer
      (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune
      form (NP-Lambert-Eaton myasthenic syndrome). Lambert-Eaton myasthenic syndrome is
      a very rare disorder in children younger than age 12 years. Herein, we report a
      25-year-old man with NP-Lambert-Eaton myasthenic syndrome, which onset was at the
      age of 10 years. To date, this is the most long-term follow-up of NP-Lambert
      Eaton myasthenic syndrome in childhood. In our patient, the only symptomatic
      treatment with 3,4-diaminopyridine phosphate has been sufficient to guarantee him
      a good quality of life. Our data remind physicians to keep in mind the diagnosis
      of Lambert-Eaton myasthenic syndrome in children with a proximal myopathic
      pattern and they confirm the specificity of compound muscle action potential
      incremental pattern after brief maximal effort in Lambert-Eaton myasthenic
      syndrome. 

PMID- 24114607
TI  - Estimating the number of young Black men who have sex with men (YBMSM) on the
      south side of Chicago: towards HIV elimination within US urban communities.
AB  - The rate of HIV infection among young Black men who have sex with men (YBMSM)
      aged 16-29 is increasing significantly in the United States. Prevention in this
      population would considerably impact future health-care resources given the need
      for lifelong antiretrovirals. A YBMSM population estimate is needed to assist HIV
      prevention program planning. This analysis estimates the number of YBMSM aged 16
      29 living on the south side of Chicago (SSC), the Chicago HIV epicenter, as the
      first step in eliminating HIV in this population. Three methods were utilized to
      estimate the number of YBMSM in the SSC. First, an indirect approach following
      the formula a = k/b; where a = the estimated number of YBMSM, k = the average
      YBMSM HIV prevalence estimate, and b = the YBMSM population-based HIV
      seropositivity rate. Second, data from the most recent National Survey of Family
      Growth (NSFG) was used to estimate the proportion of Black men who report having
      sex with a man. Third, a modified Delphi approach was used, which averaged
      community expert estimates. The indirect approach yielded an average estimate of
      11.7 % YBMSM, the NSFG yielded a 4.2 % (95 % CI 2.28-6.21) estimate, and the
      modified Delphi approach yielded estimates of 3.0 % (2.3-3.6), 16.8 % (14.5
      19.1), and 25 % (22.0-27.0); an average of 14.9 %. The crude average of the three
      methods was 10.2 %. Applied to SSC, this results to 5,578 YBMSM. The estimate of
      5,578 YBMSM represents a group that can be feasibly reached with HIV prevention
      efforts. Population estimates of those most at risk for HIV will help public
      health officials allocate resources, offering potential for elimination of new
      HIV cases. 

PMID- 24114608
TI  - Self-expanding metal stent insertion by colorectal surgeons in the management of
      obstructing colorectal cancers: a 6-year experience.
AB  - BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients
      presenting with colorectal cancer as an acute large bowel obstruction may obviate
      emergency surgery, potentially effectively palliating incurable cancers and
      acting as a bridge to surgery in patients with operable tumours. We present our
      experience with stenting for malignant acute large bowel obstruction over a 6
      year period (2006-2011). METHODS: A prospectively compiled colorectal cancer
      database was reviewed to identify all patients presenting to our unit with
      malignant acute large bowel obstruction who had stenting carried out to achieve
      colonic decompression. All 44 procedures were performed by colorectal surgeons
      using a combined endoscopic and fluoroscopic technique. RESULTS: Overall,
      successful decompression was achieved in 42 patients by SEMS insertion (95.5%).
      Technical and clinical success was achieved in all 30 patients undergoing
      stenting as a palliative measure (100%). There was no clinical perforation in any
      of the 44 patients. CONCLUSIONS: SEMSs insertion is a safe and effective
      technique for colonic decompression in the setting of acute malignant large bowel
      obstruction as either a palliative measure or as a bridge to subsequent
      resection.

PMID- 24114610
TI  - Onward to the eighth edition of TNM -- the blending of anatomic and molecular
      prognostic factors in cancer staging.

PMID- 24114612
TI  - Characterization, isolation, and culture of mouse and human spermatogonial stem
      cells.
AB  - Spermatogenesis is a special process by which spermatogonial stem cells (SSCs)
      divide and differentiate to male gametes called mature spermatozoa. SSCs are the
      unique cells because they are adult stem cells that transmit genetic information
      to subsequent generations. Accumulating evidence has demonstrated that SSCs can
      be reprogrammed to acquire pluripotency to become embryonic stem-like cells that
      differentiate into all cell lineages of the three germ layers, highlighting
      potential important applications of SSCs for regenerative medicine. Recent
      studies from peers and us have made great achievements on the characterization,
      isolation, and culture of mouse and human SSCs, which could lead to better
      understanding the biology of SSCs and the applications of SSCs in both
      reproductive and regenerative medicine. In this review, we first compared the
      cell identity and biochemical phenotypes between mouse SSCs and human SSCs.
      Notably, the cell types of mouse and human SSCs are distinct, and human SSCs
      share some but not all phenotypes with mouse SSCs. The approaches for isolating
      SSCs as well as short- and long-term culture of mouse SSCs and short-period
      culture of human SSCs were also discussed. We further addressed the new advances
      on the self-renewal of SSCs with an aim to establish the long-term culture of
      human SSCs which has not yet been achieved.

PMID- 24114613
TI  - Peripheral CD45RO, PD-1, and TLR4 expression in metastatic colorectal cancer
      patients treated with bevacizumab, fluorouracil, and irinotecan (FOLFIRI-B).
AB  - CD45RO, PD-1, and TLR4 immune pathways have proven pivotal in regulating
      antitumor response and correlate with survival for localized colorectal cancer
      (CRC). We evaluated if their peripheral expression was associated with outcome in
      metastatic CRC (mCRC). Thirty-one mCRC patients were eligible for this
      prospective study ( clinicaltrial.gov NCT01533740) and treated with first-line
      FOLFIRI-B. Blood was drawn before the first and third cycle and analyzed by flow
      cytometry for frequency (%) of CD4+, CD8+, CD45RO+, and PD1+ mononuclear cells
      and for TLR4 expression on neutrophils. Two cycles of chemotherapy determined
      changes in immune variables that were prognostically meaningful. Pre-third-cycle
      (ptc) CD45RO+CD8+cell% displayed a statistically significant association with
      progression-free survival (PFS) (median PFS 22.4 vs. 9.4 months for patients with
      CD45RO+CD8+cell%> vs. <the median value of 12%, respectively, p 0.02) and overall
      survival (OS) (2-year OS rate 62 vs. 44%, respectively, p 0.04). Surprisingly,
      ptc-PD1 overexpression was also associated with improved PFS of borderline
      statistical significance (HR 0.42, p 0.06). A Cox regression multivariate
      analysis for PFS including ptc-CD45RO+CD8+cell%, ptc-PD1+cell%, CEA, LDH, and
      Kohne risk class demonstrated CD45RO+CD8+cell% to be the only independent
      prognostic factor (HR 0.23, p 0.04). TLR4 and CD4 were not associated with the
      outcome. Peripheral CD8+CD45RO+ cells were confirmed to be of independent
      prognostic value in mCRC patients. Overexpression of the PD-1 immunosuppressor
      after two cycles of therapy may be a negative feedback mechanism, and therefore,
      an indirect sign of chemotherapy induced antitumor immune response with a
      favorable association with outcome. Enhancement of CD8+CD45RO+ cell response may
      be a fascinating therapeutic target to improve the efficacy of FOLFIRI-B.

PMID- 24114614
TI  - Efficacy of the stranger safety abduction-prevention program and parent-conducted
      in situ training.
AB  - Using a control group design, we evaluated the effectiveness of the Stranger
      Safety DVD (The Safe Side, 2004) and parent training of abduction-prevention
      skills with 6- to 8-year-old children. Children in the training or control group
      who did not demonstrate the safety skills received in situ training from their
      parents. There was no significant difference in safety skills between the
      training and control groups after the training group viewed the DVD. Children in
      both groups scored significantly better after receiving in situ training, with no
      significant difference in performance between groups. 

PMID- 24114615
TI  - Racial disparities in functional disability among older women with newly
      diagnosed nonmetastatic breast cancer.
AB  - BACKGROUND: This study sought to assess racial differences in functional
      disability among older women with nonmetastatic breast cancer. METHODS: In this
      cross-sectional study, between April 2008 and December 2012, women aged >= 65
      years with newly diagnosed stage I through III breast cancer were recruited from
      ambulatory oncology clinics at an academic center. Prior to receiving any
      adjuvant treatment, participants completed a comprehensive geriatric assessment.
      The primary outcome was functional disability, defined as dependency in any basic
      or instrumental activity of daily living, categorized as "yes" or "no." Logistic
      regression analyses were undertaken. RESULTS: The study enrolled 190 women whose
      mean age was 75.0 years at diagnosis (standard deviation = 7.0, range = 65-93
      years). Thirty-two percent were African American (AA), and 39% had functional
      disability. Controlling for age, participants with functional disability were
      more likely to be AA (versus non-Hispanic white), odds ratio = 4.19, 95%
      confidence interval = 2.12-8.27. Fifty-nine percent of the racial difference in
      functional disability was explained by a higher prevalence of lower income and
      education among AAs. In addition, the higher prevalence of chronic medical
      conditions and obesity among AAs, after accounting for socioeconomic factors,
      further explained 40% of the black-white difference in functional disability.
      CONCLUSIONS: Among older women with newly diagnosed nonmetastatic breast cancer,
      functional disability is highly prevalent, and AAs are disproportionately
      affected. Interventions to optimize the functional status of at-risk individuals,
      particularly AAs, during and after cancer treatment may improve treatment
      tolerance and overall survival outcomes.

PMID- 24114616
TI  - Insect chemoreception: a tribute to John G. Hildebrand.

PMID- 24114617
TI  - The shark Chiloscyllium griseum can orient using turn responses before and after
      partial telencephalon ablation.
AB  - This study assessed spatial memory and orientation strategies in Chiloscyllium
      griseum. In the presence of visual landmarks, six sharks were trained in a fixed
      turn response. Group 1 started from two possible compartments approaching two
      goal locations, while group 2 started from and approached only one location,
      respectively. The learning criterion was reached within 9 +/- 5.29 (group 1) and
      8.3 +/- 3.51 sessions (group 2). Transfer tests revealed that sharks had applied
      a direction strategy, possibly in combination with some form of place learning.
      Without visual cues, sharks relied solely on the former. To identify the
      underlying neural substrate(s), telencephalic were lesioned and performance
      compared before and after surgery. Ablation of the dorsal and medial pallia only
      had an effect on one shark (group 1), indicating that the acquisition and
      retention of previously gained knowledge were unaffected in the remaining four
      individuals. Nonetheless, the shark re-learned the task. In summary, C. griseum
      can utilize fixed turn responses to navigate to a goal; there is also some
      evidence for the use of external visual landmarks while orienting. Probably,
      strategies can be used alone or in combination. Neither the dorsal nor medial
      pallium seems to be responsible for the acquisition and processing of egocentric
      information. 

PMID- 24114619
TI  - Analysis of the effects of inter-individual variation in the distribution of
      plutonium in skeleton and liver.
AB  - One important parameter for biokinetic plutonium modelling is the ratio between
      the contents of plutonium in liver and skeleton. Autopsy data show a vast inter
      individual variation in the partitioning between these organs. The capacity of
      recent biokinetic models for plutonium to reproduce these variations was studied.
      Autopsy data for plutonium amounts in liver and skeleton for both (238)Pu and
      (239)Pu isotopes can be merged into a single data set following several
      statistical tests. Simulations with different parameter values generate a mapping
      between the autopsy values and the model parameters. The observed partitioning
      distribution can be transformed into a distribution of transfer rates, which
      would result in the observed data. Besides, the variation in the partitioning
      between liver and skeleton leads via biliary pathway to a variation in the
      excretion ratio. This can be used to estimate an individual partitioning factor,
      which can be used in individual case assessments. 

PMID- 24114618
TI  - Place learning prior to and after telencephalon ablation in bamboo and coral cat
      sharks (Chiloscyllium griseum and Atelomycterus marmoratus).
AB  - This study assessed complex spatial learning and memory in two species of shark,
      the grey bamboo shark (Chiloscyllium griseum) and the coral cat shark
      (Atelomycterus marmoratus). It was hypothesized that sharks can learn and apply
      an allocentric orientation strategy. Eight out of ten sharks successfully
      completed the initial training phase (by locating a fixed goal position in a
      diamond maze from two possible start points) within 14.9 +/- 7.6 sessions and
      proceeded to seven sets of transfer tests, in which sharks had to perform under
      altered environmental conditions. Transfer tests revealed that sharks had
      oriented and solved the tasks visually, using all of the provided environmental
      cues. Unintentional cueing did not occur. Results correspond to earlier studies
      on spatial memory and cognitive mapping in other vertebrates. Future experiments
      should investigate whether sharks possess a cognitive spatial mapping system as
      has already been found in several teleosts and stingrays. Following the
      completion of transfer tests, sharks were subjected to ablation of most of the
      pallium, which compromised their previously acquired place learning abilities.
      These results indicate that the telencephalon plays a crucial role in the
      processing of information on place learning and allocentric orientation
      strategies. 

PMID- 24114620
TI  - Percutaneous injection laryngoplasty.

PMID- 24114621
TI  - The genetic complexity of common cancers and the promise of personalized
      medicine: is there any hope?
AB  - Molecular characterization of frequent cancers has shown that these entities
      actually include a very large number of rare genomic diseases. The progression of
      each of these rare diseases is being driven by specific genomic alterations,
      leading to abnormal proteins that can be targeted. Based on this observation,
      several personalized medicine programmes have been launched. They consist in
      profiling the tumour samples from each patient, identifying key oncogenic
      drivers, and treating the patient accordingly. Several preliminary data suggest
      that this approach is feasible and could lead to anti-tumour effects that are
      currently modest. Several reasons could explain why personalized medicine
      programmes only report modest activity to targeted agents. First, the
      identification of key oncogenic drivers among several genomic alterations can be
      challenging. Second, the intratumour heterogeneity could lead to the emergence of
      resistant clones. Finally, several genomic alterations could contribute to cancer
      progression. These observations are leading to the second generation of
      personalized medicine trials, where targeted therapies are combined with each
      other and with immunotherapeutics, and where patients are selected to present a
      tumour with a low level of genetic instability.

PMID- 24114624
TI  - Septal perforation repair without intraoperative mucosal closure.
AB  - OBJECTIVES/HYPOTHESIS: To report a technique for septal perforation repair that
      does not rely on intraoperative mucosal closure of the perforation defect. STUDY
      DESIGN: Case series with prospective and retrospective data collection. METHODS:
      Nine patients received multilayer interposition grafts and no attempt at
      intraoperative mucosal closure for repair of septal perforations. Eight patients
      received multilayer interposition grafts consisting of temporoparietal fascia on
      one side, polydioxanone plate in the middle, and deep temporal fascia on the
      other side. One patient received a variant graft consisting of acellular dermal
      matrix, polydioxanone plate, and full-thickness temporal fascia. Silastic or
      silicone sheets were placed bilaterally for at least 12 weeks to protect the
      septum during healing. This technique was applied to a variety of challenging
      surgical candidates. RESULTS: The eight patients who received interposition
      grafts with bilateral temporal fascia had complete repair of septal perforation
      sites. The variant interposition graft had complete loss on the acellular dermal
      matrix side but good integration of temporal fascia on the contralateral side.
      CONCLUSIONS: This tension-free technique does not rely on intraoperative mucosal
      closure of the septal perforation. It has been used to successfully obtain
      complete repair in a variety of challenging surgical candidates when combined
      with temporal fascia autografts.

PMID- 24114625
TI  - [Modern pain management: is it all good, what goes? Abstracts of the German Pain
      Congress 2013. October 23-26, 2013. Hamburg, Germany].

PMID- 24114623
TI  - Current management of iron deficiency anemia in inflammatory bowel diseases: a
      practical guide.
AB  - Anemia and iron deficiency anemia are very common in inflammatory bowel disease
      (IBD). In most cases, anemia is a consequence of mixed pathogenesis; inflammation
      and iron deficiency being the most important factors. Iron status should be
      evaluated carefully, as ferritin is unreliable in the presence of inflammation.
      It is always necessary to control disease activity; however, supplementation is
      usually required to fully correct iron deficiencies. Oral iron, intravenous iron,
      erythropoietin, and blood transfusions can be used in different clinical
      scenarios. Oral iron may be used in mild cases if the disease has no clinical
      activity. Intravenous iron should be preferred where oral iron is poorly
      tolerated or where it has failed in moderate to severe anemia, and in combination
      with erythropoietin. Iron sucrose is very safe and effective, but not very
      convenient, as the total needed dose must be divided into several infusions.
      Ferric carboxymaltose is much more convenient, and has been shown to be more
      effective than iron sucrose in a large randomized trial. Iron isomaltose shows
      theoretical promise, but very limited data are available from IBD populations.
      Blood transfusion can be necessary, especially in acute life-threatening
      situations, but the trigger for indication should be in the low range. With the
      correct use of available resources, anemia and iron deficiency should be well
      controlled in practically all IBD patients. 

PMID- 24114622
TI  - Pharmacology of the new P2Y12 receptor inhibitors: insights on pharmacokinetic
      and pharmacodynamic properties.
AB  - The P2Y(12) receptor is a key player in platelet activation and represents an
      effective pharmacological target for the inhibition of platelet aggregation and
      prevention of atherothrombotic events. Indeed, the clinical use of the P2Y(12)
      receptor inhibitor clopidogrel is an effective strategy for inhibiting platelet
      activity in patients with acute coronary syndrome, and for preventing thrombotic
      events in those undergoing percutaneous coronary intervention with stenting.
      However, clopidogrel has several drawbacks, which include delayed onset of
      action, large inter-individual variability in platelet response, genetic
      polymorphism of the metabolizing enzyme, drug-drug interactions (DDIs), and the
      two-step activation process catalyzed by a series of cytochrome P450 (CYP)
      isoenzymes. For these reasons, new P2Y(12) receptor inhibitors have been
      developed in an attempt to improve on the pharmacological and clinical profile of
      clopidogrel. Three new P2Y(12) receptor inhibitors--prasugrel, cangrelor, and
      ticagrelor--have arrived, and more are coming into clinical use. Each of these
      antagonists has individual properties and, according to their mechanism of
      inhibition, can be divided into irreversible (prasugrel) and reversible
      inhibitors (ticagrelor, cangrelor). These agents also have different metabolic
      pathways: prasugrel is a prodrug that requires metabolic activation through a
      cytochrome-dependent pathway, while ticagrelor and cangrelor do not require
      metabolic conversion. However, ticagrelor is a CYP3A4 substrate/inhibitor and
      thus it can be involved in DDIs. Indeed, ticagrelor significantly increases the
      plasma levels of CYP3A4 substrates such as statins. Moreover, concomitant use
      with strong CYP3A4 inhibitors (such as ketoconazole, itraconazole,
      clarithromycin, ritonavir, telithromycin, etc.) is contraindicated, while the co
      administration of ticagrelor with potent CYP3A inducers (carbamazepine,
      rifampicin, phenytoin, phenobarbital) is discouraged. Prasugrel and ticagrelor
      determine a faster, greater, and more consistent adenosine diphosphate (ADP)
      receptor inhibition than clopidogrel, with a near complete inhibition of platelet
      aggregation between 1-2 h after administration of an oral loading dose, while
      cangrelor shows a rapid and potent platelet inhibitory effect with intravenous
      infusion. Thus, the different pharmacokinetic and pharmacodynamic characteristics
      of the P2Y(12) receptor inhibitors enable clinicians to personalize therapy
      according to patient-specific medical requirements for better prevention of
      atherothrombotic events. In the present review, we describe the pharmacological
      properties, the pharmacokinetic and pharmacodynamic differences, and the clinical
      efficacy of the currently available P2Y(12) receptor inhibitors.

PMID- 24114626
TI  - Clival keloid after nasopharyngeal radium irradiation masquerading as skull base
      malignancy.
AB  - OBJECTIVES/HYPOTHESIS: Nonchordomatous lesions of the clivus are rare entities.
      Nasopharyngeal radium irradiation (NRI) treatment consists of application of
      radium to the posterior nasopharynx near the orifice of the Eustachian tubes, an
      area adjacent to the clivus. Here we present a unique case of a patient with a
      history of NRI 70 years prior to presentation with a space-occupying clival
      lesion suspicion for a skull-based malignancy. This lesion was resected using an
      endoscopic endonasal approach. Histopathological analysis revealed a clival
      keloid, an entity not previously reported in the literature.

PMID- 24114627
TI  - Anthropometric, medical history and lifestyle risk factors for myeloproliferative
      neoplasms in the Iowa Women's Health Study cohort.
AB  - Classical myeloproliferative neoplasms (MPNs) are composed of essential
      thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), the etiology
      of which is largely unknown. We investigated the role of anthropometric, medical
      and lifestyle factors with risk of MPN in a prospective cohort of 27,370 women
      aged 55-69 years at enrollment. After >250,000 person-years of follow-up, 257
      cases of MPN were identified (172 ET, 64 PV, 21 MF). Risk factor profiles were
      mostly unique for the two most common types, ET and PV. ET was associated with
      energy balance factors including body mass index (RR = 1.52 for >29.3 vs. <23.4
      kg/m(2) ; p-trend = 0.042), physical activity (RR = 0.66 for high vs. low; p
      trend = 0.04) and adult onset diabetes (RR = 1.82; p = 0.009), while PV was not.
      PV was associated with current smoking (RR = 2.83; p-trend = 0.016), while ET was
      not. Regular use of aspirin was associated with lower risk of ET (RR = 0.68; p =
      0.017). These results broadly held in multivariate models. Our results suggest
      distinct etiologies for these MPN subtypes and raise mechanistic hypotheses
      related to obesity-related inflammatory pathways for ET and smoking-related
      carcinogenic pathways for PV. Regular aspirin use may lower risk for ET.

PMID- 24114628
TI  - Blastocyst expansion score and trophectoderm morphology strongly predict
      successful clinical pregnancy and live birth following elective single embryo
      blastocyst transfer (eSET): a national study.
AB  - PURPOSE: To determine which characteristics of blastocyst embryo morphology may
      predict clinical pregnancy and live birth rates. METHODS: A retrospective
      analysis of data from 3,151 cycles of fresh, non-donor eSET cycles from 2008 to
      2009 was performed. Data were obtained from the Society for Assisted Reproductive
      Technologies (SART) underwent. All eSET were performed at the blastocyst stage.
      Main outcome measures were clinical pregnancy and live birth rates. RESULTS:
      Trophectoderm morphology, embryo stage and patient age are highly significant
      independent predictors of both clinical pregnancy and live birth. Neither inner
      cell mass morphology nor embryo grade predicted clinical pregnancy or live birth.
      CONCLUSIONS: Better trophectoderm morphology, younger patient age and further
      blastocyst progression all result in higher clinical pregnancy and live birth
      rates. Therefore, trophectoderm morphology and blastocyst stage should
      preferentially be used as the most important factors in choosing the best embryo
      for transfer.

PMID- 24114629
TI  - Analysis of clinical outcomes with respect to spermatozoan origin after
      artificial oocyte activation with a calcium ionophore.
AB  - PURPOSE: Fertilization failures have occurred repeatedly in reproductive centers
      after intracytoplasmic sperm injection (ICSI) and artificial oocyte activation
      (AOA) has been used to prevent it. This study was performed to investigate
      whether spermatozoan origin influences clinical outcomes of AOA with a calcium
      ionophore. METHODS: A total of 185 ICSI cycles with a history of no or low
      fertilization was included in this retrospective study. The outcomes of AOA after
      ICSI were compared with ejaculated-normal, ejaculated-oligo-astheno-terato or
      extracted-testicular spermatozoa. RESULTS: There were significant differences
      between the previous standard ICSI cycles and AOA cycles in the rate of
      fertilization and clinical outcomes among cases with different sperm origins.
      Thirty-eight healthy babies (20 singles and 18 twins, 29 cycles) were
      successfully delivered, and no congenital birth defects were observed.
      CONCLUSIONS: Most patients with a no or low fertilization history obtained an
      increased fertilization rate and a positive clinical outcome with AOA regardless
      of the origin of spermatozoa.

PMID- 24114630
TI  - An interleukin-6 gene promoter polymorphism is associated with polycystic ovary
      syndrome in South Indian women.
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is a most common endocrine disorder of
      reproductive age women. Interleukin-6 is involved in the pathophysiological
      characteristics associated with polycystic ovary syndrome (PCOS). The-174 G/C IL
      6 gene promoter region single nucleotide polymorphism (SNP) may influence or
      modulate gene function and/or transcriptional efficiency. The current study was
      aimed to evaluate the association between IL-6 gene -174 G/C promoter
      polymorphism and Polycystic Ovary Syndrome in South Indian women. METHODS: In the
      present study, we examined the genotypic and allele distribution among the PCOS
      patients (n = 104) and controls (n = 156). The genotypes of IL-6 -174 G/C SNP
      were analyzed by polymerase chain reaction (PCR) and sequencing analysis. The
      allele frequency and genotype distributions of cases and controls were analyzed
      using Fisher's exact test. RESULTS: The genotype frequencies observed among the
      104 cases and 156 controls were G/G 66.3 % and 49.4 %, G/C 29.8 % and 46.8 %, and
      C/C 3.8 % and 3.8 % (OR: 1.6226, CI: 1.0574-2.4899). The G and C allele
      frequencies were 81.25 % and 72.8 %, and 18.75 % and 27.2 %, respectively. The
      genotype and allele distribution revealed significant differences between PCOS
      patients and controls (all P values < 0.05). CONCLUSION: Our findings showed a
      significant statistical association between IL-6 -174 G/C SNP and PCOS risk in
      South Indian women. The 'G' allele frequency influences significantly higher in
      PCOS patients than controls. However, the exact mechanism by which 'G' allele
      frequency influence PCOS patients is yet to be determined.

PMID- 24114633
TI  - Getting beyond the notion of genes in reproductive medicine.
AB  - As we sink ever more deeply into the realm of bioinformatics, looking beyond
      traditional genetics becomes a welcomed imperative for those seeking insights
      into the fundamental complexities that underscore our successes and failures when
      it comes to human reproduction.

PMID- 24114632
TI  - Electrical activation of rabbit oocytes increases fertilization and embryo
      development by intracytoplasmic sperm injection using sperm from deceased male.
AB  - PURPOSE: We investigated the effect of electrical stimulation on rabbit oocyte
      activation using intracytoplasmic sperm injection (ICSI) to determine whether
      viable offspring can be produced from deceased rabbit sperm using ICSI. METHODS:
      Sperm were collected from a heterozygote GFP male rabbit 5 h after sacrifice and
      cryopreserved in liquid nitrogen. Mature oocytes were fertilized using ICSI. A
      series of electrical pulse procedures were used to activate oocytes before and/or
      after ICSI. Following ICSI, zygotes were cultured in B2 medium for 4 days or
      transferred into the oviducts of recipient rabbits at the 2- or 4-cell stage.
      RESULTS: The blastocyst formation rate was significantly greater in oocytes that
      received one or two pulses prior to ICSI compared to controls and other
      electrically stimulated groups. In the single pulse before ICSI group, 23 % of
      the blastocysts expressed GFP, which was significantly greater than all other
      groups. However, those that received treatment before and after, or just
      following ICSI, showed a significant decrease in embryo survival. Finally,
      embryos from the single pulse before ICSI group were transferred into recipient
      female rabbits and a full-term kit was successfully delivered. CONCLUSIONS: One
      pulse of electrical stimulation prior to sperm injection was an effective method
      to activate rabbit oocytes for fertilization. Sperm collected from a deceased
      rabbit is able to produce viable embryos through ISCI that are capable of normal
      fetal and kit development.

PMID- 24114631
TI  - The current challenges to efficient immature oocyte cryopreservation.
AB  - Oocyte cryopreservation represents an important tool for assisted reproductive
      technology. It offers the opportunity to preserve fertility in women at risk of
      loss of the ovarian function for various pathologies. It also represents a
      treatment alternative for couples that cannot benefit from embryo
      cryopreservation because of moral, religious, or legal constrains. On the other
      hand, in vitro oocyte maturation has a range of applications. It can be applied
      in patients with a contraindication to ovarian stimulation to prevent ovarian
      hyperstimulation syndrome or to eliminate the risk of stimulation of hormone
      sensitive tumours in cancer patients. However, while mature oocyte
      cryopreservation has found wide-spread application and oocyte in vitro maturation
      has a place for the treatment of specific clinical conditions, data on the
      efficiency of freezing of immature or in vitro matured oocytes are poorer. In
      this review we will focus on the combination of oocyte in vitro maturation with
      oocyte cryopreservation with particular emphasis on the biological implications
      of the cryopreservation of immature or in vitro matured oocytes. The two
      cryopreservation approaches, slow freezing and vitrification, will be discussed
      in relation to possible cryodamage occurring to subcellular structures of the
      oocyte and the functional interaction between oocyte and cumulus cells. 

PMID- 24114635
TI  - What causes alzheimer's disease?
AB  - Since the earliest descriptions of Alzheimer's disease (AD), many theories have
      been advanced as to its cause. These include: (1) exacerbation of aging, (2)
      degeneration of anatomical pathways, including the cholinergic and cortico
      cortical pathways, (3) an environmental factor such as exposure to aluminium,
      head injury, or malnutrition, (4) genetic factors including mutations of amyloid
      precursor protein (APP) and presenilin (PSEN) genes and allelic variation in
      apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood
      brain barrier, (7) immune system dysfunction, and (8) infectious agents. This
      review discusses the evidence for and against each of these theories and
      concludes that AD is a multifactorial disorder in which genetic and environmental
      risk factors interact to increase the rate of normal aging ('allostatic load').
      The consequent degeneration of neurons and blood vessels results in the formation
      of abnormally aggregated 'reactive' proteins such as beta-amyloid (Abeta) and
      tau. Gene mutations influence the outcome of age-related neuronal degeneration to
      cause early onset familial AD (EO-FAD). Where gene mutations are absent and a
      combination of risk factors present, Abeta and tau only slowly accumulate not
      overwhelming cellular protection systems until later in life causing late-onset
      sporadic AD (LO-SAD). Abeta and tau spread through the brain via cell to cell
      transfer along anatomical pathways, variation in the pathways of spread leading
      to the disease heterogeneity characteristic of AD. 

PMID- 24114634
TI  - Th1 cytokines are more effective than Th2 cytokines at licensing anti-tumour
      functions in CD40-activated human macrophages in vitro.
AB  - CD40 agonists are showing activity in early clinical trials in patients with
      advanced cancer. In animal models, CD40 agonists synergise with T-cell-activating
      therapies to inhibit tumour growth by driving tumour macrophage repolarisation
      from an immunosuppressive to a Th1 immunostimulatory, tumouricidal phenotype. We
      therefore tested the hypothesis that T-cell-derived cytokines license anti-tumour
      functions in CD40-activated human macrophages. CD40 ligand (CD40L) alone
      activated macrophages to produce immunosuppressive IL-10, in a similar fashion to
      bacterial LPS, but failed to promote anti-tumour functions. The Th1 cytokine IFN
      gamma optimally licensed CD40L-induced macrophage anti-tumour functions, inducing
      a switch from IL-10 to IL-12p70 production, promoting macrophage-mediated Th1 T
      cell skewing and enhancing tumouricidal activity. We found that even the Th2
      cytokines IL-4 and IL-13 promoted IL-12p70 production (albeit without inhibiting
      IL-10 production) and enhanced Th1 T-cell skewing by CD40L-activated macrophages.
      However, IL-4 and IL-13 did not enhance tumouricidal activity in CD40L-activated
      macrophages. Thus, while both Th1 and Th2 cytokines biased macrophages to a Th1
      immunostimulatory phenotype, only Th1 cytokines promoted tumouricidal activity in
      CD40L-activated macrophages. The presence of tumour-infiltrating Th1 or Th2 cells
      might therefore be predictive for patient response to CD40 agonism. 

PMID- 24114636
TI  - Cellular mechanisms of white matter regeneration in an adult dysmyelinated rat
      model.
AB  - Cellular mechanisms of regeneration after the white matter injury are difficult
      to study because of severe, inflammatory response to massively damaged myelin.
      Myelin-lacking CNS of the adult Long Evans Shaker (LES) rat supplies a model
      where neuroregeneration can be studied conveniently. The crush site in the dorsal
      spinal column in LES rats implanted with the normal rat choroid plexus was
      studied under the light and electron microscopy at 5 time points 3-56 days post
      op. While the crush injury in normal rats resulted in severe inflammation active
      beyond 8 weeks, the same injury in LES rats resulted in a brief inflammation that
      resolved before day 7 post-op. In a clear fluid-filled crush cavity, ependymal
      cells from the implanted choroid plexus encased multiple regenerating axons,
      apparently guided them across the crush cavity and participated in establishing
      of a zone of neuroregeneration, morphologically similar to the white matter, at
      the interface of the crush cavity and the surrounding tissue of the spinal cord.
      Axons that were not encased by implanted cells failed to cross the crush cavity
      and persisted as markedly swollen end bulbs filled with organelles. At 8 weeks
      post-op, a large proportion of axons in the zone of neuroregeneration became
      myelinated by Schwann cells, likely originating from dorsal nerve roots or by
      oligodendrocytes that formed thin sheaths with a major dense line and likely
      originated from the implanted choroid plexus. The LES rat can serve as a
      convenient model to study mechanisms of neuroregeneration including axonal
      regeneration in the adult CNS injury. 

PMID- 24114637
TI  - Transcription factor Pax6 is expressed by astroglia after transient brain
      ischemia in the rat model.
AB  - Reactive astrogliosis is regarded as an universal astrocytic response to
      different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP)
      up-regulation, cellular hypertrophy and proliferation. The origin of reactive and
      proliferating cells in the adult brain is still disputable. Persistent
      progenitors as well as de-differentiating adult cells of various glial lineages
      are regarded as possible candidates. Pax6 transcription factor is one of the
      characteristic markers of astroglial de-differentiation, also important for
      regulation of neural and glial proliferation. Various kinds of pathological
      stimuli evoke reactive response, differentiated in its morphological, biochemical
      and immunological character. The aim of this study was to assess the dynamics of
      astroglial morphological and proliferative response to ischemic injury. One-hour
      transient focal cerebral ischemia was applied to evoke the reactive astrogliosis
      in twenty five adult male Wistar rats. The astrocytic morphological and
      proliferative reactions to ischemia were studied in the period of 6 weeks by
      means of GFAP and Pax6 immunofluorescent staining. A strong reactive astroglial
      response was observed in the cerebral cortex and striatum, manifested by GFAP and
      Pax6 up-regulation and astrocytic hypertrophy. Apparent morphological changes
      appeared within 24 hrs after ischemia. The GFAP/Pax6 colocalization was numerous
      and observed 24 hrs after ischemia. A characteristic spatial distribution of
      GFAP/Pax6 double-labelled astrocytes and Pax6 single-labelled nuclei was
      revealed, with the latter situated more distantly from the ischemic core. The
      maximal intensity of astrocytic reaction was present from the first post-ischemic
      week. Astroglial hypertrophic changes and proliferative reaction were more
      intense in the striatum than in the cerebral cortex. Our observations reveal
      intensive astroglial de-differentiation and proliferative response, reflected by
      dynamic Pax6 up-regulation within GFAP-immunoreactive astrocytes. Transient
      cerebral ischemia evokes strong reactive astrogliosis, which is apparently
      differentiated in respect to the post-ischemic period and particular brain
      structure. 

PMID- 24114638
TI  - High fructose solution induces neuronal loss in the nucleus of the solitary tract
      of rats.
AB  - Nucleus tractus solitarius (NTS) is the main region for the cardiovascular
      regulation including the baroreceptor reflex. Although the physiological and
      biochemical aspects of a high fructose diet on the brain have been studied, its
      effects on the quantitative aspects of the NTS have received less attention. The
      objective of the present study was to quantify the structural changes in the NTS
      after the consumption of high fructose solution, using stereological methods.
      Male rats were distributed randomly into two groups. One group received fructose
      (10%) in tap water for six weeks and the other one received tap water without
      fructose. The total volume of the NTS and number of the neurons of the nucleus
      were estimated using stereological methods including Cavalieri and disector
      methods. The coefficient of error (CE) of the estimators was calculated. Fasting
      plasma concentrations of glucose, triglyceride, cholesterol and insulin were
      obtained. Also a glucose tolerance test was done. The results showed no
      significant changes in glucose, triglyceride, cholesterol and insulin
      concentrations between the two groups. The glucose tolerance test did not show
      any differences, either. The mean (coefficient of variation) volume of the NTS
      and the neuronal number was 0.68 (0.2) mm3 and 68000 (0.13) in the control rats,
      respectively. But the volume of the NTS and total number of the neurons decreased
      by 41% in the fructose-treated group (p <= 0.01). Consumption of high fructose
      solution for six weeks led to a decrement in the volume and number of the neurons
      in the NTS in rats. 

PMID- 24114639
TI  - Erythrocyte transketolase activity in patients with diabetic and alcoholic
      neuropathies.
AB  - INTRODUCTION: The activity of erythrocyte transketolase induced by thiamine
      pyrophosphate and normalized to age of the patient is a marker of thiamine
      metabolism disturbances with pathological consequences in the central and
      peripheral nervous system. The measurement of erythrocyte transketolase activity
      enables evaluation of the thiamine status and therapeutic decisions in the
      disorders of the nervous system related to its deficiency. The aim of the study
      was to compare different modes of expression of transketolase activity in the
      most frequent acquired neuropathies. MATERIAL AND METHODS: The study included 29
      patients with type 2 diabetes mellitus (21 males, 8 females) aged 48.3 years
      (range: 20-70 years) and 31 subjects with a history of alcohol dependence (23
      males, 8 females) aged 54.5 years (range: 28-60 years). All participants of the
      study showed signs and symptoms of neuropathy. The cases in both groups presented
      the involvement of either axon, myelin, or both, what was evidenced by
      electrophysiological tests (electromyography and estimation of nerve conduction
      velocity). The control group consisted of 20 healthy persons aged 49.1 years
      (range: 23-70 years). Transketolase activity in erythrocytes (TK) was assessed by
      means of the spectrophotometric method. Basic TK activity was expressed as units
      per gram of haemoglobin (g Hb), moreover the normalized transketolase activity
      ratio (NTKZ) and percentage of activation of thiamine pyrophosphate (TPP) were
      calculated. RESULTS: The basal TK activity was decreased in cases with diabetic
      neuropathy (0.64 +/- 0.342 U/g Hb, p = 0.0131), whereas in patients with
      alcoholic neuropathy only a trend (p = 0.058) of the decrease was noticed (0.85
      +/- 0.484 U/g Hb), in relation to the control group (1.005 +/- 0.390 U/g Hb).
      Normalized transketolase activity ratio in erythrocytes has not shown any
      statistically significant differences. The median TPP did not indicate any
      thiamine deficiency, both in the group of diabetic and alcoholic neuropathy.
      CONCLUSIONS: The decrease in transketolase activity in diabetic neuropathy may be
      independent of thiamine deficiency. Abnormalities in transketolase activity, when
      expressed in three modalities: basal activity, normalized transketolase activity
      ratio and the activity after the stimulation with thiamine pyrophosphate may be
      differentiated as thiamine-dependent or resulting from posttranslational
      modification.

PMID- 24114640
TI  - Disturbed regulation of the isolated middle cerebral artery in acute
      hyponatremia.
AB  - Hyponatremia is a common disorder of water-electrolyte balance characterized by
      the decrease of plasma sodium ions concentration below 135 mM. Although water
      electrolyte balance is regulated by a kidney, symptoms of hyponatremia are
      related to the disturbances of intracranial homeostasis and are attributed to
      brain swelling. Despite the importance of blood vessels function for the
      homeostasis of the brain, little is known about the influence of hyponatremia on
      cerebrovascular regulation. In the present study isolated, perfused and
      pressurized rat middle cerebral arteries (MCAs) were subjected to hyponatremia in
      the organ chamber by lowering the concentration of sodium ions from 145 to 121
      mM. The response of the MCAs to the changes in intravascular pressure and to
      endothelium-dependent and independent vasodilators was compared in normo- and
      hyponatremia. The following results were obtained: the contraction of the MCA
      during progressive increases in intravascular pressure was similar in normo- and
      hyponatremia; the dilation in response to acetylcholine (10-6 M, 10-5 M and 10-4
      M), which is endothelium- and nitric oxide-dependent, was severely impaired in
      hyponatremia; the contraction after administration of the nonselective inhibitor
      of nitric oxide synthesis - NG-nitro-L-arginine methyl ester (L-NAME, 10-5 M) was
      similar in normo- and hyponatremia; the nitric oxide donor - S-nitroso-N
      acetylpenicillamine (SNAP, 10-5 M) dilated MCA only in normonatremia. The results
      of this study show that myogenic response and shear stress-dependent relaxation
      of the MCA are not affected by acute hyponatremia. However, agonist-stimulated,
      endothelial nitric oxide synthase (eNOS)-mediated relaxation is severely impaired
      which is associated with a decreased smooth muscle response to nitric oxide (NO).
      In conclusion, our results demonstrate that the regulation of isolated middle
      cerebral artery is impaired in acute hyponatremia which may contribute to the
      disturbance of intracranial homeostasis associated with hyponatremia. 

PMID- 24114641
TI  - The neuroprotective effect of long-term n-3 polyunsaturated fatty acids
      supplementation in the cerebral cortex and hippocampus of aging rats.
AB  - The purpose of this study was to determine whether hippocampus and cerebral
      cortex fatty acids (FA) composition can be altered as a result of n-3 enriched
      diet, or modifications in FA can affect the age-related histological changes in
      these brain tissues. The study was performed on eighteen rats which were fed
      control (CD) or fish oil supplemented diet (FOD) for 12 months. We investigated
      the n-3 and n-6 brain FA profile by gas-chromatography analysis. Histomorphometry
      included the measurement of the quantity of pyramidal cells in the cerebral
      cortex (layer II-III) and in the hippocampal formation (CA1, CA3 and DG). The
      number of apoptotic cells (neuron and glial cells) was also calculated separately
      in three hippocampal areas and in the pyramidal cerebral cortex layer. Rats fed
      supplemented diet showed a significantly poorer content of the arachidonic acid
      (AA, 20:4n6) in all brain regions when compared to the control group.
      Furthermore, the level of the docosahexaenoic acid (DHA, 22:6n3) was
      significantly higher in the cerebral cortex in fish oil fed rats vs. the control
      group. The neurons of the pyramidal cortex showed significant changes in cell
      density in control animals when compared to the group of fish oil fed rats.
      Furthermore, the number of positive apoptotic cells was significantly higher in
      the CA1 area and cerebral pyramidal layer in rats fed control diet. Following
      dietary n-3 fatty acids supplementation, the increase in DHA content in the
      cerebral cortex resulted in consequential changes in histology of this tissue.
      The results obtained indicate that dietary intake of fish n-3 fatty acids may
      reduce the risk of age-related brain impairments. 

PMID- 24114642
TI  - The association between cerebral amyloid angiopathy and atherosclerosis in
      patients with intracerebral hemorrhages.
AB  - aim of the study: To analyze the incidence and grade of cerebral amyloid
      angiopathy (CAA) and atherosclerosis (AS) in cerebral vessels in patients who
      died from spontaneous intracerebral hemorrhage. MATERIAL AND METHODS: The
      clinical diagnosis, based on CT scans of the brain, was made and
      immunohistochemic neuropathological examinations were performed in patients with
      intracerebral hemorrhages due to CAA. Cerebral amyloid angiopathy was diagnosed
      according to the Boston criteria. The Vonsattel and Mountoy scales were used to
      assess the grade and score of CAA. Atherosclerosis was assessed according to a
      four-grade scale presented in the Coding Guide from Collaborative Study of
      Epidemiological Factors in Cerebral Vascular Disease. RESULTS: Of the 189
      patients who died due to intracerebral hemorrhages 42 (22%) presented CAA.
      According to the Vonsattel scale this group comprised 32 (76%) patients who
      showed severe, 6 (14%) moderate and 4 (10%) mild CAA. Atherosclerosis was
      diagnosed in the CAA group of patients as follows: 6 (14%) with grade 1; 20 (49%)
      with grade 2; 9 (20%) with grade 3; and 7 (17%) patients with grade 4.
      CONCLUSIONS: There was no correlation between CAA and AS. The CAA was probably
      the direct cause of death in part of cases with advanced CAA. The different
      mechanisms presumably can cause CAA and AS.

PMID- 24114643
TI  - Circulated CD4+CD28- lymphocytes rate and their cytotoxicity and morphological
      parameters of internal carotid artery atheromatous plaques in patients with
      atherosclerosis-related ischemic stroke.
AB  - BACKGROUND: The question about the role of CD4+CD28- lymphocytes in the
      pathogenesis of atherosclerosis-related ischemic stroke is still open. MATERIAL
      AND METHODS: The study included patients, who underwent endarterectomy of
      internal carotid arteries. The group consisted of patients after stroke and ones
      without previous stroke. The histopathologic examination of obtained plaques has
      been performed. The percentage of CD4+CD28- lymphocytes in peripheral blood and
      their cytotoxicity has been assessed for each patient. RESULTS: The global
      percentage of CD4+CD28- lymphocytes in blood was higher in the group of patients
      with plaques where connective tissue fibers consisted significantly of collagen
      fibers. The cytotoxicity of analysed cells related to less plaques calcification
      and presence of cholesterol crystals in the plaque. A multifactor regression of
      dependent variable presented the last relationship above as a only strong.
      CONCLUSIONS: CD4+CD28- cytotoxic lymphocytes seem to be involved in carotid
      atherosclerotic plaques development. Intraplaque cholesterol deposits may
      contribute to this process.

PMID- 24114644
TI  - Pituitary metastases from the oncocytic variant of follicular thyroid carcinoma:
      a case report and diagnostic dilemmas.
AB  - Metastases to the pituitary gland and sella turcica are uncommon. The distinction
      between primary and secondary metastatic pituitary tumours is challenging as
      carcinomas from distant sites might closely resemble, both clinically and
      histopathologically, non-functional adenomas or primary pituitary carcinomas.
      Among metastases to pituitary gland ones from thyroid carcinoma are extremely
      rare. We present a unique case of a 53-year-old male patient with a past history
      of thyroid carcinoma who underwent repeated surgeries over a period of 7 years
      for a sellar-parasellar mass with paranasal sinus involvement. Morphologically,
      the tumour was composed of solid sheaths of monomorphic cells exhibiting
      oncocytic features. In electron microscope images, the cytoplasm of tumour cells
      was filled with numerous mitochondria. The tumour was negative for pituitary
      hormones but exhibited immunoreactivity for cytokeratin AE1/AE3, thyroglobulin
      and thyroid transcription factor 1 (TTF-1). Based on the clinical data and
      immunophenotypic profile, the tumour was finally diagnosed as an oncocytic
      variant of follicular thyroid carcinoma. To our knowledge, this is probably the
      first report of such peculiar histopathological variant of follicular thyroid
      carcinoma metastasizing to the pituitary gland. The diagnostic dilemmas
      considering oncocytic features of the presented case are discussed. 

PMID- 24114645
TI  - The coexistence of pleomorphic xanthoastrocytoma and arteriovenous malformation.
      A case report.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumour
      corresponding to WHO grade II that is usually diagnosed in adolescents and young
      adults with epileptic seizures. Pleomorphic xanthoastrocytoma typically appears
      as a superficial, often cystic mass lesion predominantly affecting the temporal
      lobe. Cases with typical pathology and total tumour excision have a favourable
      prognosis. Occasionally, the tumour reveals anaplastic features and behaves more
      aggressively due to local recurrences or subarachnoid spread. The treatment of
      PXA includes gross total resection followed by neuroradiological monitoring. The
      association between vascular malformations and cerebral gliomas is rarely
      encountered, especially if both such lesions occur as separate parts of the same
      tumour. The vascular pathology of such changes most often refers to arteriovenous
      malformation (AVM), less frequently - cavernous angioma. The coexistence of PXA
      and AVM is extremely rare, especially when dealing with two distinct patterns
      found within the same tumour mass. We present a 36-year-old woman with tumour of
      parasagittal localization in the right occipital lobe that was composed of two
      different and clearly demarcated components: PXA and vascular lesion of AVM
      morphology. The pathogenesis of such coexistence remains still unclear. 

PMID- 24114649
TI  - Attention and psychophysics in the development of stimulus control.
AB  - Rats responded in a six-stimulus, two-response temporal classification procedure.
      A successive-reversal design was used in which the relationship between stimulus
      class (short vs. long) and correct comparison location (left or right) reversed
      every 15 sessions. After several reversals, the relative probability of
      reinforcement for each correct classification was manipulated across subsequent
      reversals. In each condition, the asymptotic level of preference for the
      comparison location (response bias) correlated with the greater probability of
      reinforcement was demonstrated in the first session following a reversal, whereas
      discrimination accuracy took several more sessions to return to asymptotic
      levels. A modified version of the attending-augmented Davison-Nevin-Alsop
      (Davison & Nevin, 1999) model offered by Nevin, Davison, & Shahan (2005) provided
      an accurate description of the reacquisition data. The comparison-attending
      parameters remained high and relatively constant following reversals, while
      sample-attending parameters initially decreased following reversals, and then
      increased gradually across sessions. These findings support key assumptions of
      the attending model; sample- and comparison-attending are independent processes
      that modulate the expression of discriminative control exerted by those stimuli
      over operant behavior. 

PMID- 24114648
TI  - Phenolic-enriched fractions from brewers' spent grain possess cellular
      antioxidant and immunomodulatory effects in cell culture model systems.
AB  - BACKGROUND: Large quantities of brewers' spent grain (BSG), a co-product of the
      brewing industry, are produced annually. BSG contains hydroxycinnamic acids, and
      phenolic-rich extracts from BSG have previously demonstrated the ability to
      protect against oxidant-induced DNA damage. The present study investigated the
      anti-inflammatory potential of eight phenolic extracts from BSG: four pale (P1
      P4) and four black (B1-B4) extracts. RESULTS: BSG extracts were more cytotoxic in
      Jurkat T than U937 cells, with lower IC50 values in Jurkat T cells, measured
      using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. Pale BSG extracts P2 and P3 showed the greatest anti-inflammatory
      potential, significantly (P < 0.05) reducing interleukin-2 (IL-2), interleukin-4
      (IL-4, P2 only), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma)
      production. In addition, extracts P1-P3 and B2-B4 showed significant (P < 0.05)
      antioxidant effects, determined by the cellular antioxidant activity assays
      superoxide dismutase, catalase and glutathione content (GSH). CONCLUSION:
      Phenolic extracts from BSG, particularly the pale BSG extracts, have the ability
      to reduce a stimulated cytokine production and may also protect against cellular
      oxidative stress. Results of the present study highlight the potential of BSG
      phenolic extracts to act as functional food ingredients, providing an alternative
      use and improving the value of this brewing industry co-product.

PMID- 24114647
TI  - G protein-coupled receptors and adipogenesis: a focus on adenosine receptors.
AB  - G-protein coupled receptors (GPCRs) are a large family of proteins that
      coordinate extracellular signals to produce physiologic outcomes. Adenosine
      receptors (AR) are one class of GPCRs that have been shown to regulate functions
      as diverse as inflammation, blood flow, and cellular differentiation. Adenosine
      signals through four GPCRs that either inhibit (A1AR and A3AR) or activate (A2aAR
      and A2bAR) adenylyl cyclase. This review will focus on the role of GPCRs, and in
      particular, adenosine receptors, in adipogenesis. Preadipocytes differentiate to
      mature adipocytes as the adipose tissue expands to compensate for the consumption
      of excess nutrients. These newly generated adipocytes contribute to maintaining
      metabolic homeostasis. Understanding the key drivers of this differentiation
      process can aid the development of therapeutics to combat the growing obesity
      epidemic and associated metabolic consequences. Although much literature has
      covered the transcriptional events that culminate in the formation of an
      adipocyte, less focus has been on receptor-mediated extracellular signals that
      direct this process. This review will highlight GPCRs and their downstream
      messengers as significant players controlling adipocyte differentiation.

PMID- 24114650
TI  - Microfluidic sorting of fluorescently activated cells depending on gene
      expression level.
AB  - During the last few years, fluorescence activated cell sorter has played an
      important role in a variety of biological investigations as well as clinical
      diagnostics. However, the conventional fluorescence activated cell sorter has
      several limitations, such as large size, large sample volumes required for
      operation, and high cost. In this paper, we present a novel microfluidic device
      that can separate cells based on various fluorescent protein expression levels.
      Our system consists of three major parts: focusing, detection, and separation.
      The operating principles are briefly as follows: first fluorescent cells were
      delivered into the microfluidic chip and focused in the center of channel by
      sheath flow. Subsequently, the cells were excited by a 532 nm laser at 30 MUW and
      concurrently detected by a photomultiplier tube. Based on their fluorescence
      intensities, the cells were separated into three outlets by a dielectrophoretic
      force. Using this system, we successfully separated the genetically modified
      cells at 0.1 MUL/min (sample flow rate) to sheath flow rate at 1:5, 5 Vpp
      voltage, and 800 kHz frequency. The separation efficiency was measured as high as
      94.7%. In conclusion, we found that our system has the capability of separating
      genetically modified cells with various fluorescent intensities and help study
      biology and medicine in a molecular level. 

PMID- 24114651
TI  - A pain in the neck: lateral thyrohyoid ligament syndrome.
AB  - A lateralized pain in the neck is a common symptom encountered by the
      otolaryngologist. This complaint, frequently caused by lateral thyrohyoid
      ligament syndrome, is often misdiagnosed. The pathophysiology of this syndrome
      may relate to overuse and inflammation. [change made here after initial online
      publication]. Typically, patients present with chronic unilateral neck pain often
      associated with odynophagia. The point of maximum tenderness localizes over the
      axis of the lateral thyrohyoid ligament. We present a series of 15 patients, in
      whom treatment with depot steroid and local anesthetic injection (n = 14)
      improved symptoms in 12 (86%), with complete resolution in nine (64%) patients.

PMID- 24114652
TI  - Modeling disordered morphologies in organic semiconductors.
AB  - Organic thin film devices are investigated for many diverse applications,
      including light emitting diodes, organic photovoltaic and organic field effect
      transistors. Modeling of their properties on the basis of their detailed
      molecular structure requires generation of representative morphologies, many of
      which are amorphous. Because time-scales for the formation of the molecular
      structure are slow, we have developed a linear-scaling single molecule deposition
      protocol which generates morphologies by simulation of vapor deposition of
      molecular films. We have applied this protocol to systems comprising argon,
      buckminsterfullerene, N,N-Di(naphthalene-1-yl)-N,N'-diphenyl-benzidine, mer
      tris(8-hydroxy-quinoline)aluminum(III), and phenyl-C61-butyric acid methyl ester,
      with and without postdeposition relaxation of the individually deposited
      molecules. The proposed single molecule deposition protocol leads to formation of
      highly ordered morphologies in argon and buckminsterfullerene systems when
      postdeposition relaxation is used to locally anneal the configuration in the
      vicinity of the newly deposited molecule. The other systems formed disordered
      amorphous morphologies and the postdeposition local relaxation step has only a
      small effect on the characteristics of the disordered morphology in comparison to
      the materials forming crystals.

PMID- 24114653
TI  - Resource analysis of tonsillectomy in children.
AB  - OBJECTIVES/HYPOTHESIS: To analyze variables that affect time and cost parameters
      of pediatric adenotonsillectomy. STUDY DESIGN: Longitudinal 7-month retrospective
      review of sequential tonsil and adenoid surgery at a university pediatric
      tertiary care hospital. METHODS: All children aged 2 to 12 years who underwent
      adenotonsillectomy from May 2008 to October 2008 had charts and billing records
      analyzed for variations in charges and times of adenotonsillectomy according to
      patient age, body mass index for age (BMIFA), American Society of
      Anesthesiologists (ASA) status, surgical indication, technology used, and
      teaching status of case. A total of 214 children had records reviewed. RESULTS:
      Statistically significant variations were observed for all measured parameters
      except for indications for surgery. Children 3 years and younger had shorter
      procedures (P = .005) and total operating room times (P = .037). Charges for
      supplies were lower for ASA 1 patients than for ASA 2 patients (P = .010). Obese
      children with elevated BMIFA required longer procedures (P = .039) and more
      expensive surgery (P = .003). Procedure times were shorter for Coblation
      (ArthroCare, Austin, TX) compared with electrocautery (P = .27) and for
      microdebrider compared with electrocautery (P < .001). Charges for Coblation were
      substantially higher (P < .001). Teaching cases took longer (P < .001).
      CONCLUSIONS: Charges and times for adenotonsillectomy surgery varied by patient
      age, BMIFA, ASA status, tonsillectomy technique, and teaching case status.
      Clinically salient differences were noted for ASA status, BMIFA, and surgical
      technique. This method of cost analysis provides useful information for resource
      management in tonsillectomy.

PMID- 24114654
TI  - Somatic alterations as the basis for resistance to targeted therapies.
AB  - Recent advances in genetics and genomics have revealed new genes and pathways
      that are somatically altered in human malignancies. This wealth of knowledge has
      translated into molecularly defined targets for therapy over the past two
      decades, serving as key examples that translation of laboratory findings can have
      great impact on the ability to treat patients with cancer. However, given the
      genetic instability and heterogeneity that are characteristic of all human
      cancers, drug resistance to virtually all therapies has emerged, posing further
      and future challenges for clinical oncology. Here we review the history of
      targeted therapies, including examples of genetically defined cancer targets and
      their approved therapies. We also discuss resistance mechanisms that have been
      uncovered, with an emphasis on somatic genetic alterations that lead to these
      phenotypes.

PMID- 24114655
TI  - Selecting an appropriate caliper can be essential for achieving good balance with
      propensity score matching.
AB  - Matching on the propensity score is widely used to estimate the effect of an
      exposure in observational studies. However, the quality of the matches can be
      affected by decisions made during the matching process, particularly the order in
      which subjects are selected for matching and the maximum permitted difference
      between matched subjects (the "caliper"). This study used simulations to explore
      the effects of these decisions on both the imbalance of covariates and the
      closeness of matching, while allowing the numbers of potential matches and
      strengths of association between the confounding variable and the exposure to
      vary. It was found that, without a caliper, substantial bias was possible,
      particularly with a relatively small reservoir of potential matches and strong
      confounder-exposure association. Use of the recommended caliper reduced the bias
      considerably, but bias remained if subjects were selected by increasing or
      decreasing propensity score. A tighter caliper led to greatly reduced bias and
      closer matches, although some subjects could not be matched. This study suggests
      that a narrow caliper can improve the performance of propensity score matching.
      In situations where it is impossible to find appropriate matches for all exposed
      subjects, it is better to select subjects in order of the best available matches,
      rather than increasing or decreasing the propensity score.

PMID- 24114657
TI  - Assessing stimulus control and promoting generalization via video modeling when
      teaching social responses to children with autism.
AB  - We taught social responses to young children with autism using an adult as the
      recipient of the social interaction and then assessed generalization of
      performance to adults and peers who had not participated in the training.
      Although the participants' performance was similar across adults, responding was
      less consistent with peers, and a subsequent probe suggested that the recipient
      of the social behavior (adults vs. peers) controlled responding. We then
      evaluated the effects of having participants observe a video of a peer engaged in
      the targeted social behavior with another peer who provided reinforcement for the
      social response. Results suggested that certain irrelevant stimuli (adult vs.
      peer recipient) were more likely to exert stimulus control over responding than
      others (setting, materials) and that video viewing was an efficient way to
      promote generalization to peers. 

PMID- 24114656
TI  - Ammonia transport across the skin of adult rainbow trout (Oncorhynchus mykiss)
      exposed to high environmental ammonia (HEA).
AB  - Recent molecular evidence points towards a capacity for ammonia transport across
      the skin of adult rainbow trout. A series of in vivo and in vitro experiments
      were conducted to understand the role of cutaneous ammonia excretion (J amm)
      under control conditions and after 12-h pre-exposure to high environmental
      ammonia (HEA; 2 mmol/l NH4HCO3). Divided chamber experiments with bladder
      catheterized, rectally ligated fish under light anesthesia were performed to
      separate cutaneous J amm from branchial, renal, and intestinal J amm. Under
      control conditions, cutaneous J amm accounted for 4.5 % of total J amm in vivo.
      In fish pre-exposed to HEA, plasma total ammonia concentration increased 20-fold
      to approximately 1,000 MUmol/l, branchial J amm increased 1.5- to 2.7-fold, and
      urinary J amm increased about 7-fold. Urinary J amm still accounted for less than
      2 % of total J amm. Cutaneous J amm increased 4-fold yet amounted to only 5.7 %
      of total J amm in these fish. Genes (Rhcg1, Rhcg2, Rhbg, NHE-2, v-type H(+)
      ATPase) known to be involved in ammonia excretion at the gills of trout were all
      expressed at the mRNA level in the skin, but their expression did not increase
      with HEA pre-exposure. In vitro analyses using [(14)C] methylamine (MA), an
      ammonia analog which is transported by Rh proteins, demonstrated that MA
      permeability in isolated skin sections was higher in HEA pre-exposed fish than in
      control fish. The addition of basolateral ammonia (1,000 MUmol/l) to this system
      abolished this increase in permeability, suggesting ammonia competition with MA
      for Rh-mediated transport across the skin of HEA pre-exposed trout; this did not
      occur in skin sections from control trout. Moreover, in vitro J amm by the skin
      of fish which had been pre-exposed to HEA was also higher than in control fish in
      the absence of basolateral ammonia, pointing towards a possible cutaneous ammonia
      loading in response to HEA. In vitro MA permeability was reduced upon the
      addition of amiloride (10(-4) mol/l), but not phenamil (10(-5) mol/l) suggesting
      a role for a Na/H-exchanger (NHE) in cutaneous ammonia transport, as has been
      previously described in the skin of larval fish. Overall, it appears that under
      control conditions and in response to HEA pre-exposure, the skin makes only a
      very minor contribution to total J amm, but the observed increases in cutaneous J
      amm in vivo and in cutaneous J amm and MA permeability in vitro demonstrate the
      capacity for ammonia transport in the skin of adult trout. It remains unclear if
      this capacity may become significant under certain environmental challenges or if
      it is merely a remnant of cutaneous transport capacity from early life stages in
      these fish.

PMID- 24114658
TI  - Chimeric mice transplanted with human hepatocytes as a model for prediction of
      human drug metabolism and pharmacokinetics.
AB  - Preclinical studies in animal models are used routinely during drug development,
      but species differences of pharmacokinetics (PK) between animals and humans have
      to be taken into account in interpreting the results. Human hepatocytes are also
      widely used to examine metabolic activities mediated by cytochrome P450 (P450)
      and other enzymes, but such in vitro metabolic studies also have limitations.
      Recently, chimeric mice with humanized liver (h-chimeric mice), generated by
      transplantation of human donor hepatocytes, have been developed as a model for
      the prediction of metabolism and PK in humans, using both in vitro and in vivo
      approaches. The expression of human-specific metabolic enzymes and metabolic
      activities was confirmed in humanized liver of h-chimeric mice with high
      replacement ratios, and several reports indicate that the profiles of P450 and
      non-P450 metabolism in these mice adequately reflect those in humans. Further,
      the combined use of h-chimeric mice and r-chimeric mice, in which endogenous
      hepatocytes are replaced with rat hepatocytes, is a promising approach for
      evaluation of species differences in drug metabolism. Recent work has shown that
      data obtained in h-chimeric mice enable the semi-quantitative prediction of not
      only metabolites, but also PK parameters, such as hepatic clearance, of drug
      candidates in humans, although some limitations remain because of differences in
      the metabolic activities, hepatic blood flow and liver structure between humans
      and mice. In addition, fresh h-hepatocytes can be isolated reproducibly from h
      chimeric mice for metabolic studies.

PMID- 24114659
TI  - Hrd1 participates in the regulation of collagen I synthesis in renal fibrosis.
AB  - The production and accumulation of collagen-rich extracellular matrix are common
      hallmarks during the process of renal fibrogenesis. However, the mechanisms of
      the regulation of collagen synthesis in renal fibrosis are still unclear. Hrd1,
      an E3 ubiquitin ligase, plays important roles for protein folding in ER and
      transport to Golgi. Here, we examined the hypothesis that Hrd1
      posttranslationally regulates collagen synthesis in renal interstitial
      fibrogenesis. Unilateral ureteral obstruction induced Hrd1 expression,
      predominantly in the renal interstitium and tubular epithelium of fibrotic
      kidneys. Transforming growth factor beta1, as a key mediator in kidney fibrosis,
      significantly increased the expressions of Hrd1, alpha-smooth muscle actin,
      fibronectin as well as procollagen I and mature collagen I in dose-dependent
      manner in tubular epithelial cells, suggesting that collagen I maturation might
      be modulated during renal fibrosis. In cultured renal fibroblasts, Hrd1 knockdown
      decreased secreted collagen I ~60% in the supernatant of NRK-49F cells.
      Conversely, Hrd1 overexpression increased secreted collagen I ~1.5-fold. Hrd1
      overexpression significantly increased the expressions of both procollagen I and
      mature collagen I, ~2.2-fold and ~1.8-fold, respectively. However, Hrd1 knockdown
      markedly decreased the expression of mature collagen I ~80%, while procollagen I
      expression only was decreased ~21%. Moreover, short interfering RNA-induced
      knockdown of Sec23A blunted the increase in collagen I expression (both immature
      and mature form) by Hrd1 overexpression and returned collagen I expression toward
      control levels. These results indicate that Hrd1 plays an important role in the
      maturation of collagen I in renal fibrosis, and that Sec23A pathway is required
      for ER-to-Golgi procollagen trafficking to promote collagen synthesis.

PMID- 24114660
TI  - Antioxidant effect of doxycycline decreases MMP activity and blood pressure in
      SHR.
AB  - Increased matrix metalloproteinase (MMP) levels are involved in vascular
      remodeling of hypertension. In this study, we hypothesized that doxycycline (a
      MMP inhibitor) could exert antioxidant effects, reverse establish vascular
      remodeling, and lower blood pressure in spontaneously hypertensive rats (SHR).
      SHR and Wistar-Kyoto rats received either doxycycline at 30 mg/kg/day by gavage
      or vehicle. Systolic blood pressure (SBP) was assessed weekly by tail cuff. After
      5 weeks of treatment, morphologic changes in the aortic wall were studied in
      hematoxylin/eosin sections. MMP activity and expression were determined by in
      situ zymography using DQ gelatin and immunofluorescence for MMP-2.
      Dihydroethidium was used to evaluate aortic reactive oxygen species (ROS)
      production by fluorescence microscopy. Doxycycline reduced SBP by 25 mmHg.
      However, the antihypertensive effects were not associated with significant
      reversal of hypertension-induced vascular hypertrophy. SHR showed increased
      aortic MMP-2 levels which co-localized with higher aortic MMP activity and ROS
      levels, and all those biochemical alterations associated with hypertension were
      blunted by treatment with doxycycline. These results show that MMP inhibition
      with doxycycline in SHR with established hypertension resulted in antioxidant
      effects, lower gelatinolytic activity, and antihypertensive effects which were
      not associated with reversal of hypertension-induced vascular remodeling. 

PMID- 24114661
TI  - Pyrroloquinoline quinone inhibits oxygen/glucose deprivation-induced apoptosis by
      activating the PI3K/AKT pathway in cardiomyocytes.
AB  - The purposes of this study were to examine the protective effect of
      pyrroloquinoline quinone (PQQ) on oxygen/glucose deprivation (OGD)-induced injury
      to H9C2 rat cardiomyocytes and to investigate the mechanism. Using H9C2 cells
      cultured in vitro, we examined changes in cell viability with an MTT assay at 12,
      24, and 48 h after injury induced by OGD. Various concentrations of PQQ (1, 10,
      and 100 MUM) were added, and the effect of PQQ on cell viability after OGD was
      assessed using the MTT assay. Thus, the optimal concentration of PQQ for the
      protection of cardiomyocytes against oxygen and glucose deprivation injury was
      determined. We also used flow cytometry analysis to examine the effect of PQQ on
      H9C2 cells with OGD-induced injury. The molecular probe 2',7'-dichlorofluorescin
      diacetate was used to label the H9C2 cells, and flow cytometry was used to detect
      the effect of PQQ on reactive oxygen species (ROS) content. After labeling the
      H9C2 cells using a mitochondrial green fluorescent probe (Mito-Tracker Green), we
      measured the change in the mitochondrial content of PQQ-treated H9C2 cells.
      Western blotting was used to examine the effect of PQQ on the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the H9C2 cells. The results
      of the MTT assay showed that 48 h of OGD significantly injured the H9C2 cells (p
      < 0.01) and that treatment with 100 MUM PQQ effectively decreased the level of
      OGD-induced injury (p < 0.01). The results of the flow cytometry analysis showed
      that PQQ significantly reduced apoptosis in H9C2 cells subjected to OGD (p <
      0.05). In addition, OGD significantly increased the ROS level in H9C2 cells (p <
      0.01), and PQQ significantly inhibited this increase (p < 0.05). The results of
      the Mito-Tracker Green staining suggested that PQQ effectively inhibited the
      decrease in mitochondrial content caused by OGD (p < 0.05). Western blot analysis
      showed that PQQ partially reversed the decrease in Akt phosphorylation that was
      caused by OGD (p < 0.05). PQQ treatment dose-dependently protects H9C2 cells from
      OGD-induced injury by reducing apoptosis, decreasing intracellular ROS levels,
      and rescuing the OGD-induced decrease in mitochondrial content. The protective
      effect of PQQ may be related to its effects on the PI3K/Akt pathway. 

PMID- 24114662
TI  - PU-H71 effectively induces degradation of IkappaB kinase beta in the presence of
      TNF-alpha.
AB  - This study is to determine if PU-H71, a heat shock protein inhibitor, induces
      killing of malignant breast cells together with treatment of tumor necrosis
      factor-alpha (TNF-alpha). The related molecular mechanisms were also studied. A
      primary mammary epithelial cell line HMEC2595 cells and the highly metastatic
      breast cell line MDA-MB-231, the HER2-positive BT-474 cells, and the ER-positive
      MCF7 cells were treated with PU-H71 in the presence or absence of TNF-alpha. The
      effects of PU-H71 and TNF-alpha treatments on cells viabilities and on
      intracellular signaling pathway proteins were determined using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assays,
      immunoblot assays, and luciferase assays. It was found that TNF-alpha enhances
      the toxic effects of PU-H71 on tumor cells but not normal cells. PU-H71
      treatments lead to degradation of IKKbeta. Moreover, PU-H71 down-regulates the NF
      kappaB transcriptional activity induced by TNF-alpha treatment. The experimental
      results indicated PU-H71 effectively induces cell killing of malignant breast
      cells in the presence of TNF-alpha, possibly through a mechanism related to
      degradation of IKKbeta. It is suggested that combination of PU-H71 and TNF-alpha
      treatments might be an effective therapeutic strategy of breast malignancies. 

PMID- 24114663
TI  - Isoorientin attenuates lipopolysaccharide-induced pro-inflammatory responses
      through down-regulation of ROS-related MAPK/NF-kappaB signaling pathway in BV-2
      microglia.
AB  - Isoorientin (ISO) is a flavonoid compound in the human diet, and has been known
      to possess various bioactivities. However, the effects of ISO on microglia
      inflammation have not been investigated. The current study investigates the
      neuroprotective effect of ISO in LPS-activated mouse microglial (BV-2) cells. ISO
      significantly increased the BV-2 cells viability, blocked the protein expression
      of inducible nitric oxide synthase and cyclooxygenase-2, and decreased the
      production of nitric oxide, pro-inflammatory cytokines including tumor necrosis
      factor-alpha and interleukin-1beta. The activation of mitogen-activated protein
      kinases (MAPKs) was blocked by ISO, and NF-kappaB nuclear translocation was
      decreased by ISO both alone and together with NF-kappaB inhibitor (PDTC) and
      MAPKs inhibitors (U0126, SP 600125, and SB 203580). Furthermore, ISO strongly
      quenched intracellular reactive oxygen species (ROS) generation. ROS inhibitor (N
      acetyl cysteine, NAC) significantly inhibited pro-inflammatory cytokines release
      and NF-kappaB and MAPKs activation, indicating that ISO attenuated
      neuroinflammation by inhibiting the ROS-related MAPK/NF-kappaB signaling pathway.

PMID- 24114664
TI  - Purification of coumarin compounds from Cortex fraxinus by adsorption
      chromatography.
AB  - In this paper, a chromatographic method for isolation and purification of
      coumarin compounds from Cortex fraxinus was established by using Superose 12 as
      the separation media for the first time. The conditions for separation were
      optimized. Four kinds of coumarin compounds including aesuletin, aesculin,
      fraxetin and fraxin were obtained. The purity of these compounds were 98.5, 99.1,
      97.9 and 97.3%, respectively, which were determined by HPLC area normalization
      method. The chemical structures of the separated compounds were identified
      according to (1)H and (13)C nuclear magnetic resonance data. The retention
      behavior of the separated coumarin compounds on Superose 12 was also discussed.
      The retention is based on a mixture of hydrogen bonding and hydrophobic
      interactions between the coumarin compounds and the residues of the cross-linking
      reagents used in the manufacturing process of Superose 12. The results of this
      paper indicate that Superose 12 is not only suitable for size-exclusion
      chromatography of proteins and other biological macromolecules but also for low
      molecular-weight natural products. 

PMID- 24114665
TI  - Use of calcium supplements, vitamin D supplements and specific osteoporosis drugs
      among French women aged 75-85 years: patterns of use and associated factors.
AB  - BACKGROUND: Despite the availability of effective preventive and curative
      medications for osteoporosis, and guidelines for its diagnosis and management,
      few individuals are treated for osteoporosis, even among those who have already
      had a fracture. OBJECTIVES: Our objective was to describe the patterns of use of
      medication for osteoporosis, i.e., calcium supplements, vitamin D supplements,
      and specific anti-osteoporotic drugs, such as bisphosphonates, in a large sample
      of French older women living at home, and to identify individual factors
      associated with use of these medications overall and in two specific clinical
      situations. METHODS: Cross-sectional analysis of data from 4,221 women aged 75-85
      years who participated in a balance and mobility examination as part of the
      screening procedure for the Ossebo study, a randomized controlled trial testing
      the effectiveness of exercise for the prevention of fall-related injuries.
      Electoral rolls were used to invite women in 16 towns to participate
      (participation rate 10.3 %). Information collected through questionnaires
      included current medication use and, in particular, use of osteoporosis
      medications (specific osteoporosis drugs, calcium and vitamin D supplementation)
      in the past 6 months, and history of fracture since the age of 50, including
      fracture locations. Fractures were categorized in three groups: no fracture,
      major osteoporotic fracture (hip, humerus, wrist, pelvis, and vertebra), and
      other fracture. RESULTS: Nearly 48 % of the participants reported they did not
      take calcium or vitamin D supplements or any specific osteoporosis drugs. Of the
      2,133 women who reported using osteoporosis medication, 85 % used vitamin D
      supplements (25 % as the sole medication against this disease), 59 % calcium
      supplements, and 42 % a specific anti-osteoporotic drug (75 % of them combining
      it with vitamin D supplementation). The use of any osteoporosis medication was
      significantly associated (p < 0.001) with a history of a major osteoporotic
      fracture, lower weight, dual-energy X-ray absorptiometry (DXA) bone-density
      measurement in the past 5 years, a cancer-screening examination in the past 5
      years, and a positive attitude toward medication use in general. Living alone was
      associated with a lower likelihood of using a specific anti-osteoporotic drug,
      and a higher education level was associated with a higher likelihood of vitamin D
      supplementation. Of the 1,553 women who had already had a major osteoporotic
      fracture, one-third (34.8 %) were not taking any osteoporosis medication. In this
      subgroup, use of this medication was associated with the same factors as in the
      overall study population. In particular, neither older age nor a history of falls
      in the previous 12 months was associated with a higher likelihood of using
      osteoporosis medication. Among the 909 women who reported using a specific
      osteoporosis drug, vitamin D use was associated with a higher educational level
      and a more frequent preventive attitude. CONCLUSION: In France, as in other
      western countries, women aged 75 years and over are not managed according to
      guidelines. Further studies should address the barriers encountered in improving
      quality of care in osteoporosis management.

PMID- 24114666
TI  - Integrating research into dental student training: a global necessity.
AB  - The integration of research into dental education is necessary to ensure that
      evidence-based practice reaches the clinical setting and that dentistry remains a
      scientifically driven health profession. Consequently, dental accreditation
      standards in the United States and Canada require dental schools to integrate
      research components into curricula. Organizations (e.g., NIDCR, ADEA, AADR, IADR,
      and NSRG) provide some opportunities for dental students to experience research.
      Assessment of the integration of research into dental curricula suggests that US
      students are interested in learning and utilizing evidence-based practice, but
      lack adequate time for research participation. Records show limited student
      involvement in research organizations internationally (i.e., AADR and IADR).
      Vague accreditation standards and limited research opportunities outside of
      dental schools may be barriers. We lack an understanding of the status of
      integration of research into dental curricula internationally, but predict that
      similar issues exist. We propose that dental institutions consider implementing
      the following: (1) curriculum components to assess the use of evidence-based
      practice, (2) faculty and student seminars for discussing evidence-based
      practice, (3) subsidization of student membership in dental research
      organizations (e.g., AADR and IADR), and (4) sponsorship of students as
      institutional representatives at annual research meetings (e.g., IADR, AADR, ADA,
      and ADEA meetings), with subsequent school-wide dissemination of knowledge
      attained from attendance. 

PMID- 24114667
TI  - Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity
      and breast cancer?
AB  - Women with breast cancer (BC) and antithyroid peroxidase (TPO) autoantibodies
      (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with
      TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not
      apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that
      provides a target for humoral or cell-mediated immune activity; candidates
      include the sodium/iodide symporter (expressed in thyroid and BC), cross-reacting
      epitopes in TPO and lactoperoxidase (LPO) or TPO itself. As the association is
      with TPOAb, we investigated TPO expression in BC, breast peritumoral tissue (PT),
      other tissues (tumoral and not) and thyroid as positive control. Transcripts for
      known and novel TPO isoforms were detected in BC (n = 8) and PT (n = 8) but at
      approximately 10(4) -fold lower than in thyroid while in non-BC tumors (n = 5)
      they were at the limit of detection. TPO was expressed also in adipose tissue (n
      = 17), 10(3) -fold lower than in thyroid. Full length TPO (Mr 105-110 kDa) was
      detected in Western blots in the majority of examined tissues; preabsorption of
      the TPO antibody with recombinant TPO (but not LPO) reduced the signal,
      indicating specificity. The same occurred with some lower molecular weight bands,
      which could correspond to smaller TPO transcript isoforms, present in all
      samples. In conclusion, TPO is weakly expressed in BC and other tissues; this
      could partly explain the high frequency and protective role of TPOAb in BC
      patients. Further studies will investigate tissue specificity, function and
      immunogenicity of the novel TPO variants (some BC-specific) identified.

PMID- 24114668
TI  - Intermittent versus continuous erlotinib with concomitant modified "XELOX" (q3W)
      in first-line treatment of metastatic colorectal cancer: correlation with serum
      amphiregulin and transforming growth factor alpha.
AB  - BACKGROUND: This study evaluated the activity of 2 schedules of erlotinib in
      combination with chemotherapy, and the prognostic significance of serum
      amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic
      colorectal cancer. METHODS: A total of 60 untreated patients were randomized to a
      "continuous" (CON; erlotinib 100 mg daily) or an "intermittent" (INT; erlotinib
      150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21)
      schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin)
      regimen. Serum levels of AREG and TGFa were determined serially. RESULTS:
      Baseline characteristics were similar between the 2 arms. Of the 58 patients
      evaluated for response, there was a nonsignificant trend toward a slightly higher
      overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a
      median follow-up of 2.8 years, the median overall survival was 18.8 months (95%
      confidence interval = 11.3-22.9 months) and 20.7 months (95% confidence interval
      = 12.5-31 months, P = .19) for the CON and INT arm, respectively. KRAS mutation
      did not predict drug response. The 2 arms did not differ significantly in
      toxicity. Baseline serum TGFa was an independent predictor of progression-free
      survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of
      treatment were associated with shorter progression-free survival and overall
      survival, respectively. CONCLUSIONS: The intermittent erlotinib schedule was
      associated with a higher response rate, although this is not statistically
      significant. Serum TGFa and AREG levels have prognostic significance in erlotinib
      treated patients with colorectal cancer, and further studies are warranted.

PMID- 24114669
TI  - Outcome with immediate direct anastomosis of recurrent laryngeal nerves injured
      during thyroidectomy.
AB  - OBJECTIVES/HYPOTHESIS: Management of unrecognized recurrent laryngeal nerve
      injury typically entails delayed phonosurgical intervention and laryngeal
      reinnervation, but in cases of recognized injury, nerve anastomosis has been
      considered standard management. However, the well-organized outcome analysis of
      nerve anastomosis has been insufficient. We performed immediate direct
      anastomosis of recurrent laryngeal nerves injured during surgery for thyroid
      cancer, and subsequent patient outcomes were analyzed. STUDY DESIGN: A total 14
      patients sustaining recurrent laryngeal nerve injury during thyroidectomy were
      recruited for the study. Patients undergoing immediate direct reparative
      anastomosis of the injured nerves constituted the test group, whereas the
      controls of group 2 (n = 4) did not. METHODS: At follow-up, all patients
      submitted to rigid laryngoscopy at 3, 6, and 12 months postoperatively.
      Subjective and objective outcomes of the two groups were then compared. RESULTS:
      At 12 months postoperatively, group 1 showed greater improvement in maximum
      phonation time, glottic gap scores, GRBAS (grade, roughness, breathiness,
      asthenia, and strain) scales, aspiration scoring, and Voice Handicap Index than
      controls of group 2. Moreover, group 1 showed an improvement in all five
      categories at 12 months postoperatively, compared with status at 3 months. None
      of the patients in group 1 showed laryngoscopic evidence of vocal cord atrophy.
      CONCLUSION: In this study, patients undergoing immediate direct recurrent
      laryngeal nerve anastomosis demonstrated better phonation and perceptually rated
      voice quality than those who did not undergo repair. LEVEL OF EVIDENCE: 3b.

PMID- 24114670
TI  - Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by
      improving its bioavailability and pharmacokinetics.
AB  - BACKGROUND: Mangiferin is a xanthonoid present in Mangifera indica. It has been
      reported for a variety of pharmacological activities, including hepatoprotection.
      However, the major disadvantage of mangiferin is its reduced biological activity
      due to poor absorption, low bioavailability and rapid elimination from the body
      after administration. The aim of this study was to prepare a phospholipid complex
      of mangiferin to overcome these limitations and to investigate the impact of the
      complex on hepatoprotective activity and bioavailability. RESULTS: The results
      showed that the complex has an enhanced hepatoprotective and in vivo antioxidant
      activity as compared to pure mangiferin at the same dose level (30 and 60 mg kg
      1). The complex restored the levels of serum hepatic marker enzymes and liver
      antioxidant enzymes with respect to carbon tetrachloride-treated animals. The
      complex also increased the bioavailability of mangiferin in rat serum by 9.75
      fold compared to pure mangiferin at the same dose level and enhanced the
      elimination half-life (t(1/2 el)) from 1.71 +/- 0.12 h-1 to 3.52 +/- 0.27 h-1.
      CONCLUSION: The results suggested that the complexation of mangiferin with soya
      phospholipid enhanced the hepatoprotection and in vivo antioxidant activity,
      which may be due to the improved bioavailability and pharmacokinetics of
      mangiferin in rat serum.

PMID- 24114671
TI  - Longitudinal study of lower urinary tract function in children with anorectal
      malformation.
AB  - Neurogenic bladder dysfunction (NBD) in children with anorectal malformation
      (ARM) has been reported in many publications, but with variations in prevalence
      and connection to type of ARM and spinal cord/sacral malformations. The
      prevalence of ARM patients with functional nonneurogenic dysfunction, on the
      contrary, has been addressed only sparsely. Since constipation and soiling have
      been shown to often accompany functional urinary tract symptoms in children
      without malformations, and treatment of constipation often improves bladder
      symptoms, it is interesting to assess such a connection in ARM patients. This
      study assessed lower urinary tract dysfunction (LUTD) overall in ARM children.
      Special attention was paid to whether patients with poor bowel function had more
      LUT symptoms, excluding those with urological reasons for the LUTD (NBD and
      urogenital malformations). PATIENTS AND METHODS: Children with ARM, excluding
      those with perineal fistula, were included (n = 41). Bladder function was
      investigated at 5 (n = 25), 10 (n = 28), and 15 (n = 13) years using a structured
      questionnaire and flow residual. A scoring system was used. In addition, healthy
      children of comparable age were assessed using the same questionnaire. Data on
      bowel function were also available, as presented in a recent article. In children
      with NBD, cystometry was also used at follow-up. RESULTS: NBD was seen in 9
      children (22%), whereas nonneurogenic LUTD was diagnosed in 14 cases (34%). A
      clear difference between the groups was seen, with a permanent dysfunction in
      neurogenic and often transient and mild in the nonneurogenic LUTD. A significant
      correlation between LUTD and bowel dysfunction was identified when all LUTD was
      included (p = 0.045). When children with neurogenic and urological causes of LUTD
      were excluded, the remaining children with LUTD had lower scores for bowel
      function than those with normal bladder function, but the difference was not
      significant (p = 0.1291). CONCLUSION: Poor bowel function was often seen together
      with LUTD. In children with NBD, the connection was attributable to a mutual
      impairment of the nerve supply to both systems. Children with nonneurogenic and
      nonurological causes of the LUTD also had lower bowel scores than those with
      normal bladder function; although not significant, it suggests that poor bowel
      function was responsible for an increase in LUT symptoms.

PMID- 24114672
TI  - Identification of a microsporidian isolate from Cnaphalocrocis Medinalis and its
      pathogenicity to Bombyx mori.
AB  - A microsporidian, CmM2, was isolated from Cnaphalocrocis medinalis. The
      biological characters, molecular analysis and pathogenicity of CmM2 were studied.
      The spore of CmM2 is long oval in shape and 3.45 +/- 0.25 * 1.68 +/- 0.18 um in
      size, the life cycle includes meronts, sporonts, sporoblasts, and spores, with
      typical diplokaryon in each stage, propagated in binary fission. There is
      positive coagulation reaction between CmM2 and the polyclonal antibody of Nosema
      bombycis (N.b.). CmM2 spores is binuclear, and has 10-12 polar filament coils.
      The small subunit ribosomal RNA (SSU rRNA) gene sequence of CmM2 was obtained by
      PCR amplification and sequencing, the phylogenetic tree based on SSU rRNA
      sequences had been constructed, and the similarity and genetic distance of SSU
      rRNA sequences were analyzed, showed that CmM2 was grouped in the Nosema clade.
      The 50% infectious concentration of CmM2 to Bombyx mori is 4.72 * 10(4)  spores
      ml(-1) , and the germinative infection rate is 12.33%. The results showed that
      CmM2 is classified into genus Nosema, as Nosema sp. CmM2, and has a heavy
      infectivity to B. mori. The result indicated as well that it is valuable
      taxonomic determination for microsporidian isolates based on both biological
      characters and molecular evidence. 

PMID- 24114673
TI  - Control of the Asian tiger mosquito (Aedes albopictus) in a firmly established
      area in Spain: risk factors and people's involvement.
AB  - BACKGROUND: The tiger mosquito is a competent vector of dengue and chikungunya in
      Europe. Therefore, evaluating control strategies is a priority. In this work we
      aimed to determine the key factors affecting Aedes albopictus production, the
      preferred larval habitats, and we explored the involvement of the citizens in
      Sant Cugat, Spain. METHODS: A source-reduction campaign including door-to-door
      visits and interviews to local inhabitants (2008-2010) and larval surveys (2010)
      was carried out. RESULTS: Civil workers inspected 3720 premises and interviewed
      820 local inhabitants. Larval habitats, detected in 7.2% of the premises (n=266),
      were negatively associated with primary residence OR=0.4 (95% CI 0.3-0.6); and
      positively associated with schools OR=2.4 (95% CI 1.1-5.0), solid waste OR=5.1
      (95% CI 3.0-8.9), scuppers OR=5.0 (95% CI 3.5-7.3) among other variables.
      Preventive measures were taken by 83.2% of householders (n=682). In 2010, 10.3%
      more citizens claimed to avoid having stagnant water compared with 2008.
      Simultaneously another 10.3% stopped using insecticides. CONCLUSION: Solid waste,
      scuppers and vegetable gardens were found to be important factors characterizing
      premises with larval habitats. People claimed to know about this insect and they
      considered it to be an important issue that diminished their quality of life.

PMID- 24114674
TI  - Should mortality data for the elderly be collected routinely in emergencies? The
      practical challenges of age-disaggregated surveillance systems.
AB  - Data on the elderly are rarely collected in humanitarian emergencies. During a
      refugee crisis in South Sudan, Medecins Sans Frontieres developed a prospective
      mortality surveillance system collecting data for those aged >=50 years and found
      that the elderly were dying at five times the rate of those aged 5-49 years.
      Practical and ethical issues arose. Were reported ages accurate? Since no
      baseline exists, what does the mortality rate mean? Should programmatic changes
      be made without evidence that these would reduce the elderly mortality rate? We
      outline issues to be addressed to enable informed decisions on response to
      elderly populations in emergency settings. 

PMID- 24114676
TI  - Ultrasonic surgical aspirator-assisted phonosurgery: a novel technique for
      laryngeal cartilage dissection.

PMID- 24114675
TI  - Activated CD4+ T cells enter the splenic T-cell zone and induce autoantibody
      producing germinal centers through bystander activation.
AB  - CD4(+) T (helper) cells migrate in huge numbers through lymphoid organs. However,
      little is known about traffic routes and kinetics of CD4(+) T-cell subsets within
      different organ compartments. Such information is important because there are
      indications that CD4(+) T cells may influence the function of microenvironments
      depending on their developmental stage. Therefore, we investigated the migration
      of resting (naive), activated, and recently activated (memory) CD4(+) T cells
      through the different compartments of the spleen. Resting and recently activated
      CD4(+) T cells were separated from thoracic duct lymph and activated CD4(+) T
      cells were generated in vitro by cross-linking the T-cell receptor and CD28. The
      present study shows that all three CD4(+) T-cell subsets selectively accumulate
      in the T-cell zone of the spleen. However, only activated T cells induce the
      formation of germinal centers (GCs) and autoantibodies in rats and mice. Our
      results suggest that in a two-step process they first activate B cells
      independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression.
      The activated B cells then form GCs whereby CD154-dependent T-cell help is
      needed. Thus, activated T cells may contribute to the development of autoimmune
      diseases by activating autoreactive B cells in an Ag-independent manner.

PMID- 24114679
TI  - Treatment for perforated gastric ulcer: a multi-institutional retrospective
      review.
AB  - BACKGROUND: The optimal treatment for patients with perforated gastric ulcer
      (PGU) remains controversial. This study therefore investigated the treatment
      status for this disease in clinical practice. METHODS: We retrospectively
      reviewed 183 patients with PGU from 1998 to 2007 across 15 institutions, and
      analyzed patient characteristics and short- and long-term outcomes according to
      treatments received. RESULTS: Of the 183 patients, 57 who were treated
      conservatively had less abdominal tenderness, lower levels of serum C-reactive
      protein, and shorter time to presentation than the 126 patients who underwent
      emergency surgery. There was no significant difference in baseline
      characteristics between the 41 successful patients and 16 failed patients in the
      conservative treatment group; however, the latter had a longer average hospital
      stay. Eighty-three of the emergency surgery patients who underwent gastrectomy
      had longer surgical times, greater blood loss, and shorter time to resumption of
      diet than the 57 patients undergoing stomach-preserving surgery; however, there
      was no significant difference in postoperative complications and hospital stay
      between these groups. Of 91 patients who received stomach-preserving treatment,
      only three had treatment failure in the long-term follow-up period. CONCLUSION:
      Strictly selected patients should be initially considered for conservative
      treatment. The short-term outcomes of stomach-preserving surgery are comparable
      to gastrectomy; however, further evaluation of the long-term outcomes of stomach
      preserving treatment is required.

PMID- 24114677
TI  - Identification and use of biomarkers in treatment strategies for triple-negative
      breast cancer subtypes.
AB  - Triple-negative breast cancer (TNBC) is a heterogeneous disease with distinct
      molecular subtypes that respond differentially to chemotherapy and targeted
      agents. The absence of high-frequency molecular alterations and a limited number
      of known biomarkers have limited the development of therapeutic strategies for
      the disease. Herein, we summarize the results of the first round of targeted
      therapy approaches in TNBC and discuss new preclinical strategies. Common themes
      emerge from the proposed strategies, such as the use of biomarkers to identify
      tumours with genomic instability, targeting adapted molecular states resulting
      from tumour suppressor loss, and targeting altered metabolic pathways.

PMID- 24114680
TI  - Clinical outcomes for neuroendocrine tumors of the duodenum and ampulla of Vater:
      a population-based study.
AB  - BACKGROUND: Previous case series report that neuroendocrine tumors (NETs) of the
      ampulla of Vater have worse overall survival (OS) than NETs in the duodenum. We
      aimed to compare the OS of patients with ampullary NETs to patients with duodenal
      NETs. METHODS: This retrospective comparative cohort study used the Surveillance,
      Epidemiology, and End Results (SEER) registry from 1988 to 2009. OS was evaluated
      using Kaplan-Meier estimates and Cox proportional hazard regression. RESULTS:
      Ampullary NETs (n = 120) were larger (median size 18 vs. 10 mm, p < 0.001),
      higher grade (poorly and undifferentiated tumor 42 % vs. 12 %, p < 0.001), higher
      SEER historic stage (distant metastasis 16 % vs. 7 %, p < 0.001), and more often
      resected (78 % vs. 60 %, p < 0.001) than duodenal NETs (n = 1,360). Median OS was
      significantly worse for patients with ampullary NETs than with duodenal NETs (98
      vs. 143 months, p = 0.037). Local resection was performed for 50.5 % of the
      resected ampullary NETs and resulted in similar OS compared to locally resected
      duodenal NETs (HR 1.37, 95 % CI 0.76-2.48, p = 0.291). CONCLUSIONS: While
      ampullary NETs are more advanced at presentation and have worse OS than duodenal
      NETs, long-term survival is possible with proximal small bowel NETs. For locally
      resected NETs, OS is similar between ampullary and duodenal NETs.

PMID- 24114681
TI  - Laparoscopic splenectomy: perioperative management, surgical technique, and
      results.
AB  - Since their introduction in the early 1990s, minimally invasive techniques have
      gained widespread acceptance because of the significant benefits that patients
      are able to experience. Some of these benefits include reduced postoperative
      pain, earlier return to normal activity, and improved cosmesis when compared with
      open surgery. For these reasons, since its first description by Delaitre and
      Maignien in 1991, laparoscopic splenectomy (LS) has been increasingly utilized
      for a safe surgical removal of the spleen with nearly equivalent or superior
      short- and long-term outcomes when compared with the open approach. In this
      technical report, we aim to describe our preoperative and postoperative
      management of patients undergoing LS and to illustrate our preferred surgical
      technique, its rationale, and our results.

PMID- 24114682
TI  - Short-term but not long-term loss of patency of venous reconstruction during
      pancreatic resection is associated with decreased survival.
AB  - BACKGROUND: Pancreatic surgery with vascular reconstruction is increasingly
      performed to offer the benefits of surgical resection to patients with locally
      advanced disease. The short- and long-term patency rates and the clinical
      significance of thrombosis of such reconstructions are unknown. METHODS: We
      reviewed pancreatectomies requiring venous reconstruction from 1994 to 2011. We
      sought to identify predictors of acute (within 30 days) and late thrombosis. We
      compared survival of patients with thrombosis to patients with patent
      reconstructions. RESULTS: Of 203 pancreatectomies requiring venous
      reconstruction, acute thrombosis occurred in nine (4.4 %) cases and was
      associated with increased perioperative mortality (22.2 versus 4.6 %, p = 0.023).
      Even when nonfatal, acute thrombosis was associated with decreased median
      survival (7.1 versus 15.9 months, p = 0.011) and increased hazard of death
      (hazard ratio 8.6, confidence interval 3.7-19.9, p < 0.001). A late loss of
      patency was seen in 31.2 % of cases at a median of 9.5 months. Later loss of
      patency was not associated with decreased median survival or increased hazard of
      death. CONCLUSIONS: Acute thrombosis of the portal venous reconstructions after
      pancreatectomy is associated with increased perioperative mortality and, even
      when nonfatal, is associated with decreased survival. Late loss of patency occurs
      in one-third of patients but does not affect survival.

PMID- 24114684
TI  - Atrial fibrillation: A kiss of death?

PMID- 24114685
TI  - Main results of the ESC Congress 2013, Amsterdam: moving or standstill in
      cardiology?

PMID- 24114683
TI  - Selective decontamination of the digestive tract in gastrointestinal surgery:
      useful in infection prevention? A systematic review.
AB  - INTRODUCTION: Gastrointestinal surgery is associated with a high incidence of
      infectious complications. Selective decontamination of the digestive tract is an
      antimicrobial prophylaxis regimen that aims to eradicate gastrointestinal
      carriage of potentially pathogenic microorganisms and represents an adjunct to
      regular prophylaxis in surgery. MATERIAL AND METHODS: Relevant studies were
      identified using bibliographic searches of MEDLINE, EMBASE, and the Cochrane
      database (period from 1970 to November 1, 2012). Only studies investigating
      selective decontamination of the digestive tract in gastrointestinal surgery were
      included. RESULTS: Two randomized clinical trials and one retrospective case
      control trial showed significant benefit in terms of infectious complications and
      anastomotic leakage in colorectal surgery. Two randomized controlled trials in
      esophageal surgery and two randomized clinical trials in gastric surgery reported
      lower levels of infectious complications. CONCLUSION: Selective decontamination
      of the digestive tract reduces infections following esophageal, gastric, and
      colorectal surgeries and also appears to have beneficial effects on anastomotic
      leakage in colorectal surgery. We believe these results provide the basis for a
      large multicenter prospective study to investigate the role of selective
      decontamination of the digestive tract in colorectal surgery.

PMID- 24114686
TI  - ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and
      cardiac myofilament function (ENGINE study).
AB  - INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart
      disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is
      characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence
      of another cardiac or systemic disease. At present it lacks specific treatment to
      prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and
      HCM patients. Previous studies have indicated that sarcomere mutations increase
      energetic costs of cardiac contraction and cause myocardial dysfunction and
      hypertrophy. By using a translational approach, we aim to determine to what
      extent disturbances of myocardial energy metabolism underlie disease progression
      in HCM. METHODS: Hypertrophic obstructive cardiomyopathy (HOCM) patients and
      aortic valve stenosis (AVS) patients will undergo a positron emission tomography
      (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with
      tissue tagging before and 4 months after myectomy surgery or aortic valve
      replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to
      determine efficiency of sarcomere contraction in-vitro, and results will be
      compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic
      HCM mutation carriers will serve as a control group. ENDPOINTS: Our study will
      reveal whether perturbations in cardiac energetics deteriorate during disease
      progression in HCM and whether these changes are attributed to cardiac
      remodelling or the presence of a sarcomere mutation per se. In-vitro studies in
      hypertrophied cardiac muscle from HOCM and AVS patients will establish whether
      sarcomere mutations increase ATP consumption of sarcomeres in human myocardium.
      Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired
      cardiac energetics are restored by cardiac surgery.

PMID- 24114687
TI  - Let's talk about sex : (title of a song from 1991 by 'Salt 'n Pepa').

PMID- 24114688
TI  - In vivo deletion of CAR resulted in high bone mass phenotypes in male mice.
AB  - Constitutive androstane receptor (CAR) was originally identified as xenobiotic
      sensor that regulates the expression of cytochrome P450 genes. However, recent
      studies suggest that this nuclear receptor is also involved in the regulation of
      energy metabolism including glucose and lipid homeostasis. This study
      investigated the role of CAR in the regulation of bone mass in vivo using CAR(-/
      ) mice. Endogenous mRNA expression of CAR was observed in both primary
      osteoblasts and osteoclast precursors. CAR(-/-) mice have exhibited significant
      increase in whole body bone mineral density (BMD) by 9.5% (P < 0.01) and 5.5% (P
      < 0.05) at 10 and 15 weeks of age, respectively, compared with WT mice in males.
      Microcomputed tomography analysis of proximal tibia demonstrated a significant
      increase in trabecular bone volume (62.7%), trabecular number (54.1%) in male
      CAR(-/-) mice compared with WT mice. However, primary culture of calvarial cells
      exhibited no significant changes in osteogenic differentiation potential between
      CAR(-/-) and WT. In addition, the number of tartrate-resistant acid-phosphatase
      positive osteoclasts in the femur and serum level of CTx was not different
      between CAR(-/-) and WT mice. The higher BMD and microstructural parameters were
      not observed in female mice. Interestingly, serum level of testosterone in male
      CAR(-/-) mice was 2.5-fold higher compared with WT mice and the mRNA expressions
      of Cyp2b9 and 2b10 in the liver, which regulate testosterone metabolism, were
      significantly down-regulated in male CAR(-/-) mice. Furthermore, the difference
      in BMD between CAR(-/-) and WT mice disappeared at 8 weeks after performing
      orchiectomy. CAR(-/-) mice also exhibited significant increase in serum 1,25(OH)2
      D3 levels but Cyp 27B1 which converts 25(OH)D3 to 1,25(OH)2 D3 was significantly
      down-regulated compared to WT mice. These results suggest that in vivo deletion
      of CAR resulted in higher bone mass, which appears to be a result from reduced
      metabolism of testosterone due to down-regulation of Cyp2b.

PMID- 24114689
TI  - A high-sensitivity LIF detector with silver mirror coating detection window and
      small-angle optical deflection from collinear system for CE.
AB  - An LIF detector was integrated into a CE system based on silver mirror coating
      detection window and small-angle optical deflection from collinear configuration.
      For this detection scheme, the incident light beam was focused on capillary
      through the edge of a lens, resulting in a small deflection angle that deviated
      18 degrees  from the collinear configuration. Meanwhile, the excitation light and
      emitted fluorescence were effectively reflected by silver mirror coating at the
      detection window. The fluorescence was collected through the center of the same
      lens and delivered to a PMT in the vertical direction. In contrast to
      conventional collinear LIF detection systems, the fluorescence intensity was
      greatly enhanced and the background level was significantly eliminated. FITC and
      FITC-labeled amino acids were used as model analytes to evaluate the performance
      with respect to design factors of this system. The limit LOD was estimated to be
      0.5 pM for FITC (S/N = 3), which is comparable to that of optimized confocal LIF
      systems. All the results indicate that the proposed detection scheme will be
      promising for development of sensitive and low-cost CE system. 

PMID- 24114690
TI  - Use of olfactory training in post-traumatic and postinfectious olfactory
      dysfunction.
AB  - OBJECTIVES/HYPOTHESIS: There is evidence that the olfactory system can be
      modulated by repeated exposure to odors, a procedure called olfactory training.
      The aim of this study was to assess the effectiveness of olfactory training in
      patients with postinfectious and post-traumatic olfactory dysfunction. STUDY
      DESIGN: Prospective study of 119 patients with postinfectious and post-traumatic
      olfactory dysfunction. METHODS: Two groups of patients (postinfectious and post
      traumatic) performed the olfactory training (n = 49 and n = 23, respectively)
      over a period of 16 weeks and were compared with two control groups of the same
      etiology (n = 32 and n = 15). Patients with sinunasal, neurologic, or idiopathic
      disease were excluded. Training was performed twice daily with the use of four
      odors (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon],
      and eugenol [cloves]). Olfactory testing was performed by means of the Sniffin'
      Sticks test battery (threshold, discrimination, identification) at the time of
      diagnosis, and 8 and 16 weeks later. All patients evaluated their olfactory
      function by means of a visual analogue scale (0-100). RESULTS: Compared to
      controls, training patients in both groups presented significantly higher scores
      of olfactory function as measured by the Sniffin' Sticks test. This increase was
      measured in 67.8% of postinfectious and 33.2% of post-traumatic patients.
      Subjective ratings were in accordance with the olfactory test results. Subset
      analysis showed that olfactory function mainly increased olfactory identification
      followed by discrimination in both training groups. CONCLUSIONS: The present
      study suggests that a 16-week short-term exposure to specific odors may increase
      olfactory sensitivity in patients with postinfectious and post-traumatic
      olfactory dysfunction.

PMID- 24114691
TI  - Comparing thulium laser and Nd:YAG laser in the treatment of genital and urethral
      condylomata acuminata in male patients.
AB  - BACKGROUND: To date therapies for condylomata acuminata of the male genital are
      known for high recurrence rates and bothersome side effects, while urethral warts
      are not always reachable by most traditional therapies. OBJECTIVE: To compare the
      clinical outcomes in the treatment of condylomata acuminata on the male external
      genitalia and/or urethra using the Thulium laser and the Neodymium:Yttrium
      Aluminum Garnet laser (Nd:YAG). METHODS: From January 1994 to January 2013, 76
      men with condylomata acuminata on the external genitalia or within the urethra
      were treated with the Nd:YAG laser and 39 men with the Thulium laser. Primary
      clearance rate, relapse characteristics and complications were investigated
      retrospectively and compared. RESULTS: Of the total of 115 patients, 39 patients
      (34%) developed recurrences, of which 13 in the Thulium laser group en 26 in the
      Nd:YAG laser group. Two patients in the Thulium group and four in the Nd:YAG
      group had minor complications. CONCLUSION: This first report of the treatment of
      condylomata acuminata with the Thulium laser shows that it is a safe and
      effective treatment for condylomata, both on the external genitalia and in the
      urethra. The recurrence rate is comparable to the Nd:YAG laser and there have
      been minimal complications as a result of minimal scarring.

PMID- 24114692
TI  - Recombination and evolutionary dynamics of human echovirus 6.
AB  - Enterovirus (EV) infections are associated with a wide array of often severe
      disease presentations including aseptic meningitis, encephalitis, and acute
      flaccid paralysis. Surveillance for polioviruses and other EVs is therefore
      important as a public health measure both for patient management and
      epidemiological studies. From 1988 to 2008, echovirus (E) 30 was the predominant
      genotype in Spain (33.7% of the total typed EVs). E6 was also endemic throughout
      this period although isolated less frequently (12.5%). In 2009, however, a
      substantial increase in the incidence of E6 was detected (60%), displacing E30
      type (2%). To investigate the evolution and recombination in the epidemiology and
      transmission of E6 in Spain, a genetic analysis in VP1 and 3Dpol regions of 67
      Spanish strains collected during the period 2004-2010 was performed. All VP1
      sequences clustered monophyletically in the assigned genogroup C, subgroup 9,
      currently the predominant circulating strains identified in Europe and elsewhere
      in the last 10 years. 3Dpol sequences were interspersed with other species B EVs
      resulting from several recombination events that generated at least 12 different
      recombinant forms (RFs) among study samples. These showed typically minimal
      divergence in VP1. The co-circulation of different lineages of E6 in the same
      geographical area associated with its mainly endemic pattern of transmission may
      have contributed to the extremely short estimated half-life of E6 RFs (0.87
      years). This pattern contrasts markedly with other species B EVs and EV71 where
      VP1 lineage expansion and extinction occurred in step with defined recombination
      events and periodic changes in incidence.

PMID- 24114693
TI  - Effectiveness of using noncontingent escape for general behavior management in a
      pediatric dental clinic.
AB  - In a randomized controlled trial, 151 children 2 to 9 years old were exposed to
      either usual behavior management or to a fixed-time schedule of brief breaks
      (noncontingent escape) from ongoing dental treatment. Results demonstrated that
      the routine delivery of scheduled breaks from treatment significantly reduced the
      vocal and physical disruptive behavior and the need for restraint in a
      nonclinical sample of children undergoing restorative dental treatment. In
      addition, the treatment did not add significantly to the typical time spent on
      behavior management by dentists. Together with findings from previous studies,
      these results suggest that using brief breaks from ongoing dental treatment has
      good efficacy, acceptability, and generality and may be a useful management tool,
      both in everyday dental practice and in more demanding instances of specialized
      need. 

PMID- 24114694
TI  - Giant cell tumor of bone in childhood: clinical aspects and novel therapeutic
      targets.
AB  - Giant cell tumor of bone (GCTB) is a rare primary bone tumor that primarily
      affects young adults, but can be seen in children. The primary modality of
      treatment is surgical resection; however, this is not always possible given the
      location and extent of the neoplasm. Recent developments in the understanding of
      the underlying molecular pathogenesis of disease have pointed to interactions
      between the stromal component producing receptor activator of nuclear factor
      kappaB (RANK) and RANK-ligand (RANKL) causing the formation of osteoclast-like
      giant cells that drive bone destruction. The development of a monoclonal
      humanized antibody to RANKL, denosumab, has been shown to reduce skeletal-related
      events from osteoporosis and from bony metastases from solid tumors. Recent phase
      II clinical trials with denosumab in skeletally mature adolescents over age 12
      years and adults with GCTB, have shown both safety and efficacy, leading to its
      accelerated US FDA approval on 13 June 2013. In children who are skeletally
      immature, safety and efficacy has not been established, and there has been only
      published anecdotal use. 

PMID- 24114696
TI  - Expression of the truncated tissue plasminogen activator (K2S) gene in tobacco
      chloroplast.
AB  - As because the plant plastid genome is highly polyploid, the transformation of
      chloroplasts permits the introduction of thousands of copies of foreign genes per
      plant cell and generates extraordinarily high levels of recombinant protein.
      Human tissue-type plasminogen activator is one of the most important
      pharmaceutical proteins involved in the breakdown of blood clots in brain and
      heart blood vessels. We report the introduction and expression of the truncated
      human tissue plasminogen activator (K2S) gene in tobacco chloroplasts. The K2S
      containing vector pKCZK2S was successfully transferred to tobacco plastomes using
      the biolistic delivery procedure. Transplastomic plants were selected on RMOP
      medium containing spectinomycin (500 mg/l). In order to achieve homoplasmy,
      several rounds of selection and regeneration were performed. The presence, site
      specific integration, homoplasmy, expression and activity assay of the transgene
      were confirmed in the transplastomic plants by PCR, Southern-blot, RT-PCR, SDS
      PAGE, ELISA, Dot-blot, Western-blot and zymography analysis. Our results show
      that the tissue plasminogen activator (K2S form) protein to be expressed in
      tobacco chloroplasts in active form.

PMID- 24114697
TI  - In vivo study on the effects of curcumin on the expression profiles of anti
      tumour genes (VEGF, CyclinD1 and CDK4) in liver of rats injected with DEN.
AB  - In this study we investigated the effects of curcumin, derived from plant Curcuma
      longa, on oxidative toxicity, and the possible molecular mechanism of antitumour
      of curcumin in liver cancer rats. Results showed that blood levels of Gamma
      glutamyltransferase, aspartate aminotransferase, alanine aminotransferase,
      glutathione S-transferase, and liver level of MD were significantly decreased
      after curcumin feeding. Levels of the liver malondialdehyde MDA, nitric oxide and
      antioxidant enzymes were significantly increased. Moreover, RT-PCR and Western
      blot analysis results showed that curcumin treatment significantly decreased
      liver vascular endothelial growth factor (VEGF), CyclinD1 and CDK4 mRNA
      expression levels and CyclinD1 and CDK4 proteins levels in liver cancer rats.
      These findings were confirmed by histopathology. It is concluded that curcumin
      can protect the liver from the damage caused by N-nitrosodiethylamine. Moreover,
      curcumin has the potential to be used in a therapy for liver cancer. The present
      data provide evidence to support the presence of free radicals and VEGF, CyclinD1
      and CDK4 mRNA in rat tumour cells. Studies are in progress in order to further
      characterize the role of VEGF, CyclinD1 and CDK4 mRNA in liver cancer cells and
      in hepatic therapeutics. 

PMID- 24114698
TI  - Estimation of thigh muscle cross-sectional area by single- and multifrequency
      segmental bioelectrical impedance analysis in the elderly.
AB  - Bioelectrical impedance analysis (BIA) has been used to estimate skeletal muscle
      mass, but its application in the elderly is not optimal. The accuracy of BIA may
      be influenced by the expansion of extracellular water (ECW) relative to muscle
      mass with aging. Multifrequency BIA (MFBIA) can evaluate the distribution between
      ECW and intracellular water (ICW), and thus may be superior to single-frequency
      BIA (SFBIA) to estimate muscle mass in the elderly. A total of 58 elderly
      participants aged 65-85 years were recruited. Muscle cross-sectional area (CSA)
      was obtained from computed tomography scans at the mid-thigh. Segmental SFBIA and
      MFBIA were measured for the upper legs. An index of the ratio of ECW and ICW was
      calculated using MFBIA. The correlation between muscle CSA and SFBIA was moderate
      (r = 0.68), but strong between muscle CSA and MFBIA (r = 0.85). ECW/ICW index was
      significantly and positively correlated with age (P < 0.001). SFBIA tends to
      significantly overestimate muscle CSA in subjects who had relative expansion of
      ECW in the thigh segment (P < 0.001). This trend was not observed for MFBIA (P =
      0.42). Relative expansion of ECW was observed in older participants. The relative
      expansion of ECW affects the validity of traditional SFBIA, which is lowered when
      estimating muscle CSA in the elderly. By contrast, MFBIA was not affected by
      water distribution in thigh segments, thus rendering the validity of MFBIA for
      estimating thigh muscle CSA higher than SFBIA in the elderly. 

PMID- 24114695
TI  - Drug treatment of pulmonary hypertension in children.
AB  - Pulmonary arterial hypertension (PAH) is a rare disease in infants and children
      that is associated with significant morbidity and mortality. The disease is
      characterized by progressive pulmonary vascular functional and structural changes
      resulting in increased pulmonary vascular resistance and eventual right heart
      failure and death. In the majority of pediatric patients, PAH is idiopathic or
      associated with congenital heart disease and rarely is associated with other
      conditions such as connective tissue or thromboembolic disease. Although
      treatment of the underlying disease and reversal of advanced structural changes
      has not yet been achieved with current therapy, quality of life and survival have
      been improved significantly. Targeted pulmonary vasodilator therapies, including
      endothelin receptor antagonists, prostacyclin analogs, and phosphodiesterase type
      5 inhibitors, have demonstrated hemodynamic and functional improvement in
      children. The management of pediatric PAH remains challenging, as treatment
      decisions continue to depend largely on results from evidence-based adult studies
      and the clinical experience of pediatric experts. This article reviews the
      current drug therapies and their use in the management of PAH in children. 

PMID- 24114699
TI  - Chronic measurement of left ventricular pressure in freely moving rats.
AB  - Measurements of left ventricular pressure (LVP) in conscious freely moving
      animals are uncommon, yet could offer considerable opportunity for understanding
      cardiovascular disease progression and treatment. The aim of this study was to
      develop surgical methods and validate the measurements of a new high-fidelity,
      solid-state pressure-sensor telemetry device for chronically measuring LVP and
      dP/dt in rats. The pressure-sensor catheter tip (2-Fr) was inserted into the left
      ventricular chamber through the apex of the heart, and the telemeter body was
      implanted in the abdomen. Data were measured up to 85 days after implant. The
      average daytime dP/dt max was 9,444 +/- 363 mmHg/s, ranging from 7,870 to 10,558
      mmHg/s (n = 7). A circadian variation in dP/dt max and heart rate (HR) was
      observed with an average increase during the night phase in dP/dt max of 918 +/-
      84 mmHg/s, and in HR of 38 +/- 3 bpm. The beta-adrenergic-agonist isoproterenol,
      beta1-adrenergic agonist dobutamine, Ca(2+) channel blocker verapamil, and the
      calcium sensitizer levosimendan were administered throughout the implant period,
      inducing dose-dependent time course changes and absolute changes in dP/dt max of 
      6,000 to +13,000 mmHg/s. The surgical methods and new technologies demonstrated
      long-term stability, sensitivity to circadian variation, and the ability to
      measure large drug-induced changes, validating this new solution for chronic
      measurement of LVP in conscious rats.

PMID- 24114701
TI  - Regulation of cellular metabolism: programming and maintaining metabolic
      homeostasis.
AB  - Mitochondrial oxidative phosphorylation is programmed to set and maintain
      metabolic homeostasis. This is accomplished through an intrinsic program that
      determines the metabolic [ATP]/[ADP]/[Pi], where [Pi] is the concentration of
      inorganic phosphate (energy state) and maintains it through a bidirectional
      sensory/signaling control network that reaches every aspect of cellular
      metabolism. The program sets the energy state with high precision (to better than
      one part in 10(9)) and can respond to transient changes in energy demand (ATP
      use) to more than 100 times the resting rate. Epigenetic and environmental
      factors are able to "fine tune" the programmed set point over a narrow range to
      meet the special needs associated with cell differentiation and chronic changes
      in metabolic requirements. The result is robust, across platform control of
      metabolism, essential to cellular differentiation and the evolution of complex
      organisms. 

PMID- 24114700
TI  - Time-frequency methods and voluntary ramped-frequency breathing: a powerful
      combination for exploration of human neurophysiological mechanisms.
AB  - We experimentally altered the timing of respiratory motoneuron activity as a
      means to modulate and better understand otherwise hidden human central neural and
      hemodynamic oscillatory mechanisms. We recorded the electrocardiogram, finger
      photoplethysmographic arterial pressure, tidal carbon dioxide concentrations, and
      muscle sympathetic nerve activity in 13 healthy supine young men who gradually
      increased or decreased their breathing frequencies between 0.05 and 0.25 Hz over
      9-min periods. We analyzed results with traditional time- and frequency-domain
      methods, and also with time-frequency methods (wavelet transform, wavelet phase
      coherence, and directional coupling). We determined statistical significance and
      identified frequency boundaries by comparing measurements with randomly generated
      surrogates. Our results support several major conclusions. First, respiration
      causally modulates both sympathetic (weakly) and vagal motoneuron (strongly)
      oscillations over a wide frequency range-one that extends well below the
      frequency of actual breaths. Second, breathing frequency broadly modulates vagal
      baroreflex gain, with peak gains registered in the low frequency range. Third,
      breathing frequency does not influence median levels of sympathetic or vagal
      activity over time. Fourth, phase relations between arterial pressure and
      sympathetic and vagal motoneurons are unaffected by breathing, and are therefore
      likely secondary to intrinsic responsiveness of these motoneurons to other
      synaptic inputs. Finally, breathing frequency does not affect phase coherence
      between diastolic pressure and muscle sympathetic oscillations, but it augments
      phase coherence between systolic pressure and R-R interval oscillations over a
      limited portion of the usual breathing frequency range. These results refine
      understanding of autonomic oscillatory processes and those physiological
      mechanisms known as the human respiratory gate. 

PMID- 24114702
TI  - Evidence of active regulation of cerebral venous tone in individuals undergoing
      embolization of brain arteriovenous malformations.
AB  - Cerebral venous drainage is generally believed to be regulated primarily by
      hydrodynamic forces. To gain further insight into the regulation of this process,
      we investigated the response of blood flow velocity and cross-sectional area
      (CSA) of the internal jugular veins (IJVs) to local hemodynamic shifts. All
      procedures and assessments were performed on patients (n = 30) undergoing
      embolization of brain arteriovenous malformations (AVMs). The procedure
      efficiency was verified by the postembolization reduction in time-averaged
      maximum blood flow velocities, as well as the elevation of pulsatility index and
      resistance index in the arterial feeders. In cerebral veins, the dominant IJV
      pressure remained unchanged during the procedure. At the same time, AVM
      embolization caused a significant reduction in maximal CSA (84 +/- 7.6 to 68 +/-
      7.7 mm(2), P < 0.05) and minimal CSA (68 +/- 7.0 to 51 +/- 7.0 mm(2), P < 0.01)
      of the IJV located ipsilateral to the AVM, while the maximal linear blood flow
      velocity in the IJV remained unchanged (71 +/- 4.9 and 85 +/- 8.4 cm/s, P =
      0.098). Consistent with previously published studies, the data obtained provide
      further evidence of active regulation of the venous outflow, probably mediated by
      certain neurogenic and/or endothelium-dependent mechanisms. 

PMID- 24114703
TI  - Less is more: blunted responses to hypoxia revealed in sea-level Tibetans.

PMID- 24114704
TI  - Tetraplegia is a risk factor for central sleep apnea.
AB  - Sleep-disordered breathing (SDB) is highly prevalent in patients with spinal cord
      injury (SCI); the exact mechanism(s) or the predictors of disease are unknown. We
      hypothesized that patients with cervical SCI (C-SCI) are more susceptible to
      central apnea than patients with thoracic SCI (T-SCI) or able-bodied controls.
      Sixteen patients with chronic SCI, level T6 or above (8 C-SCI, 8 T-SCI; age 42.5
      +/- 15.5 years; body mass index 25.9 +/- 4.9 kg/m(2)) and 16 matched controls
      were studied. The hypocapnic apneic threshold and CO2 reserve were determined
      using noninvasive ventilation. For participants with spontaneous central apnea,
      CO2 was administered until central apnea was abolished, and CO2 reserve was
      measured as the difference in end-tidal CO2 (PetCO2) before and after. Steady
      state plant gain (PG) was calculated from PetCO2 and VE ratio during stable
      sleep. Controller gain (CG) was defined as the ratio of change in VE between
      control and hypopnea or apnea to the DeltaPetCO2. Central SDB was more common in
      C-SCI than T-SCI (63% vs. 13%, respectively; P < 0.05). Mean CO2 reserve for all
      participants was narrower in C-SCI than in T-SCI or control group (-0.4 +/- 2.9
      vs.-2.9 +/- 3.3 vs. -3.0 +/- 1.2 l.min(-1).mmHg(-1), respectively; P < 0.05). PG
      was higher in C-SCI than in T-SCI or control groups (10.5 +/- 2.4 vs. 5.9 +/- 2.4
      vs. 6.3 +/- 1.6 mmHg.l(-1).min(-1), respectively; P < 0.05) and CG was not
      significantly different. The CO2 reserve was an independent predictor of apnea
      hypopnea index. In conclusion, C-SCI had higher rates of central SDB, indicating
      that tetraplegia is a risk factor for central sleep apnea. Sleep-related
      hypoventilation may play a significant role in the mechanism of SDB in higher SCI
      levels. 

PMID- 24114705
TI  - Serpin B5 is a CEA-interacting biomarker for colorectal cancer.
AB  - Serpin B5 is a candidate tumour suppressor, but its oncogenic activity has also
      been reported. Its function may be affected by protein interactions. The aim of
      this study was to assess the relationship between serpin B5 and carcinoembryonic
      antigen (CEA) expression in colorectal cancer (CRC). We also analysed the
      clinicopathological significance of serpin B5 expression in patients with CRC.
      Downregulation of serpin B5 was identified in a CEA-suppressed LoVo cell line
      using two-dimensional gel electrophoresis (2-DE) and matrix-associated laser
      desorption ionisation-mass spectrometry (MALDI-MS). The specific interaction and
      co-localisation of serpin B5 with CEA were confirmed by co-immunoprecipitation
      and confocal microscopy. Western blot analysis and ELISAs revealed significant
      positive correlations between levels of serpin B5 and CEA in human colon cancer
      cell lines and in the blood of patients with CRC. Tissue expression of serpin B5
      in 377 patients with CRC was significantly associated with serum CEA,
      histological grade, stage, lymph node metastasis, lymphatic and perineural
      invasion, and infiltrative border. Strong expression of serpin B5 was also
      associated with a reduced DFS (p = 0.001) and OS (p = 0.017). Together, these
      findings describe a relationship between serpin B5 and CEA expression in CRC.
      Strong expression of serpin B5 was associated with a worse prognosis in patients
      with CRC and its expression may correlate with CEA levels in CRC. 

PMID- 24114706
TI  - Genes and schizophrenia: from a Festschrift Seminar honoring William T. Carpenter
      Jr, MD.
AB  - Recent data have begun to elucidate the genetic architecture of schizophrenia, as
      well as provide new insights into the relationships of specific genetic factors
      across diagnostic boundaries, with specific symptom domains, and in the
      prediction of antipsychotic treatment response. Not surprisingly, work conducted
      at the Maryland Psychiatric Research Center (MPRC), led by Dr William Carpenter,
      has helped to guide the thinking behind much of this work, as well as contributed
      valuable data toward these efforts. In this article, I will briefly summarize
      some of the major findings emerging from these lines of research and highlight
      the role of the Dr Carpenter and his colleagues at the MPRC in this area. 

PMID- 24114707
TI  - An immunochromatographic assay for rapid and direct detection of 3-amino-5
      morpholino-2-oxazolidone (AMOZ) in meat and feed samples.
AB  - BACKGROUND: Furaltadone (FTD) is a type of nitrofuran and has been banned in many
      countries as a veterinary drug in food-producing animals owing to its potential
      carcinogenicity and mutagenicity. FTD is unstable in vivo, rapidly metabolizing
      to 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ); thus AMOZ can be used as an
      indicator for illegal usage of FTD. Usually, for the determination of
      nitrofurans, the analyte is often a derivative of the metabolite rather than the
      metabolite itself. In this study, based on the monoclonal antibody (mAb) against
      AMOZ, a competitive immunochromatographic assay (ICA) using a colloidal gold-mAb
      probe for rapid and direct detection of AMOZ without a derivatization step in
      meat and feed samples was developed. RESULTS: The intensity of red color in the
      test line is inversely related to the analyte concentration and the visual
      detection limit was found to be 10 ng mL-1. The performance of this assay was
      simple and convenient because the tedious and time-consuming derivatization step
      was avoided. The ICA detection was completed within 10 min. The ICA strips could
      be used for 7 weeks at room temperature without significant loss of activity. The
      AMOZ spiked samples were detected by ICA and confirmed by enzyme-linked
      immunosorbent assay. The results of the two methods were in good agreement.
      CONCLUSION: The proposed ICA provides a feasible tool for simple, sensitive,
      rapid, convenient and semi-quantitative detection of AMOZ in meat and feed
      samples on site. To our knowledge, this is the first report of the ICA for direct
      detection of AMOZ.

PMID- 24114708
TI  - Facial disfigurement: restoration of facial dynamics in a patient with
      concomitant facial paralysis and blindness.

PMID- 24114709
TI  - Medial sural artery perforator free flap: legitimate use as a solution for the
      ipsilateral distal lower extremity defect.
AB  - The medial sural artery perforator (MSAP) flap captures the cutaneous territory
      of the medial calf, and can potentially be advantageous as a thin free flap, even
      in the most obese individual, for coverage of most foot and/or ankle defects
      where bulk is a liability. The anatomy is fairly constant, as usually at least
      one reasonably large perforator can always be found emanating from the medial
      head of the gastrocnemius muscle. As a microsurgical tissue transfer, a long
      vascular pedicle of large caliber is routinely possible which facilitates any
      requisite microanastomoses.Over the past decade from our free flap registry, 14
      patients with distal lower extremity wounds were covered specifically with a
      perforator flap based on the ipsilateral medial sural artery; out of which only 2
      (14%) were females.In this series using a MSAP free flap, there was only one
      failure requiring salvage by a different free flap. All but one case was a sequel
      of trauma, and these involved all zones of the foot and ankle. A skin graft of
      the donor site was necessary in 5/14 (36%) patients. In no cases did the flap
      subsequently impede the use of shoes nor hinder ambulation.The study concluded
      the major disadvantage of the MSAP flap is the nonaesthetic scar left at the
      donor site which can be quite conspicuous, especially if a skin graft had to be
      used. Yet even this detriment can be acceptable for ipsilateral distal lower
      extremity defects where reconstruction of the defect itself may be cosmetically
      unappealing. This may be the best indication for the MSAP flap to be considered
      first as the free flap of choice. 

PMID- 24114710
TI  - Intraoperative transfusion of packed red blood cells in microvascular free tissue
      transfer patients: assessment of 30-day morbidity using the NSQIP dataset.
AB  - Although often a life-saving therapeutic maneuver, there is minimal data
      available that details the effects of intraoperative packed red blood cell
      transfusion (IOT) after microvascular free tissue transfer. The National Surgical
      Quality Improvement Program database was queried to identify all patients who
      underwent microvascular free tissue transfer between 2006 and 2010. Multivariate
      logistic regression models were used to determine the association between
      intraoperative transfusion and outcomes. Upon bivariate and multivariate
      analyses, IOT was significantly associated with higher rates of overall
      complications (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.12-3.63),
      medical complications (OR, 3.35; 95% CI, 1.75-6.42), postoperative transfusion
      (OR, 6.02; 95% CI, 2.02-17.97), and reoperation (OR, 2.24; 95% CI, 1.24-4.04).
      IOT was not associated with either surgical complications or free flap loss. IOT
      significantly increases risk for adverse overall and medical complications.
      However, IOT was not associated with surgical complications or free flap loss.
      Transfusion practices in the operating room should be reevaluated to improve
      overall outcomes. 

PMID- 24114711
TI  - Vocal fold pseudocyst: results of 46 cases undergoing a uniform treatment
      algorithm.
AB  - OBJECTIVES/HYPOTHESIS: To describe treatment results and identify predictors of
      the need for surgical intervention in patients with vocal fold pseudocyst. STUDY
      DESIGN: Retrospective cohort study with longitudinal followup via survey.
      METHODS: Clinical records were reviewed for demographic information, VHI-10
      score, and degree of severity of dysphonia. Videostroboscopic examinations were
      evaluated for presence of vocal fold pseudocyst, along with additional clinical
      variables, including laterality, reactive lesion, paresis, varix, and hemorrhage.
      Follow-up surveys were sent to all participants to evaluate current VHI-10 score
      and degree of vocal limitation. Results were analyzed to determine predictors of
      surgery and recurrence of pathology. RESULTS: Forty-six patients (41F:5M) with
      pseudocyst (40 unilateral: 6 bilateral) were reviewed. Twenty-three (50%) had
      reactive lesions, nineteen (41%) had paresis by clinical criteria, 10 (22%) had
      varices, and 6 (13%) had hemorrhage on examination. All underwent initial
      behavioral management (2-12 sessions of voice therapy; mean of 8 sessions).
      Seventeen (37%) eventually required surgical intervention. No demographic or
      clinical variables proved predictive of surgical intervention. Follow-up surveys
      were completed by 63% of patients, and 79% agreed with the statement that they
      were not professionally limited by their voices. CONCLUSION: This experience
      supports behavioral management as an initial intervention in patients with
      pseudocyst, sufficient by itself to restore vocal function in approximately two
      out of three patients. Neither initial severity nor any of the studied clinical
      findings predicted the need for surgery. The large majority of patients with
      pseudocyst are able to be treated effectively without impact in their
      professional function.

PMID- 24114712
TI  - Is total duration of distal compound muscle action potential better than negative
      peak duration in the diagnosis of chronic inflammatory demyelinating
      polyneuropathy?
AB  - INTRODUCTION: The diagnosis of chronic inflammatory demyelinating polyneuropathy
      (CIDP) is difficult, and the role of electrophysiology is crucial. Distal
      compound muscle action potential (CMAP) duration is a useful tool that is
      assessed by measuring negative peak duration (NP). The value of total distal CMAP
      duration (T), which seems more precise from a physiological standpoint, has not
      been studied. METHODS: We reviewed retrospectively the records of 50 patients
      with CIDP and 50 controls with chronic axonal neuropathy. We constructed ROC
      curves for NP and T. RESULTS: Comparison of AUC for T vs. NP showed an advantage
      for the former (P=0.026 for the fibular nerve). Our derived cut-offs offered a
      sensitivity of 42.3% for T vs. 35.3% for NP. CONCLUSION: This study suggests a
      slight advantage for T over NP duration of the distal CMAP in the diagnosis of
      CIDP. However, the clinical relevance of this result must be weighed against the
      feasibility of this measurement.

PMID- 24114713
TI  - Fatty acid profiles of Vibrio parahaemolyticus and its changes with environment.
AB  - The fatty acid (FA) profiles of 15 strains representing four genera (Vibrio,
      Pseudomonas, Aeromonas, and Shewanella) and seven species were compared by
      capillary gas chromatography with flame ionization detection. FA fingerprints of
      Vibrio parahaemolyticus were established by similarity calculation and principle
      component analysis. This provided a simple measure for distinguishing V.
      parahaemolyticus from other bacteria. The similarity scores indicated by
      correlation coefficient and vector cosine were divided into three regions and
      suggested that the strains with scores higher than 0.980 probably belonged to V.
      parahaemolyticus. However, samples with low scores (<0.850) were classified under
      other genera. Furthermore, the alterations in FA profiles of V. parahaemolyticus
      in the presence of various environmental pressures were investigated. The
      production of saturated FA (SFA) increased gradually concomitant with a decreased
      proportion of unsaturated FA (UFA) with rising temperature. Similarly, the SFA
      tended to increase at the expense of UFA with prolonged culture time. In
      addition, V. parahaemolyticus changed its FA profiles to contain increased short
      chained FA to resist an acidic environment, whereas alkaline conditions
      stimulated high production of long-chained FA. Analysis on FA profile is valuable
      for the physiological study of V. parahaemolyticus and its rapid identification. 

PMID- 24114715
TI  - An animal model of obstructive sleep apnea in rabbit.
AB  - OBJECTIVES/HYPOTHESIS: An animal model of obstructive sleep apnea (OSA) may help
      to investigate the pathophysiology of this disorder and develop appropriate
      treatments. We investigated the feasibility of a rabbit model of OSA. STUDY
      DESIGN: Animal study. METHODS: Twelve New Zealand white rabbits were injected at
      the base of their tongues under endoscopic guidance with liquid silicone
      (experimental group, n = 6) or normal saline (control group, n = 6).
      Polysomnography was performed before and after injection. The development of OSA
      and changes in sleep parameters were compared between the two groups. RESULTS:
      Before injection, all rabbits showed normal breathing during sleep without
      hypopnea. In the silicone group, the rabbits had a mean of 29.9 +/- 6.9
      hypopneas/hour and a mean of 10.4 +/- 3.1 apneas/hour 1 month after silicone
      injection and 28.4 +/- 6.9 hypopneas/hour and 10.0 +/- 3.3 apneas/hour 3 months
      after silicone injection (P < 0.05). Mean total sleep time decreased from 260.3
      +/- 70.2 minutes at baseline to 152.5 +/- 38.8 minutes 1 month and 206.8 +/- 60.3
      minutes 3 months after injection, with a decrease in stage II sleep. In the
      saline group, however, there were no breathing events during sleep. CONCLUSIONS:
      These results show that silicone injections into the tongue base of rabbits can
      result in OSA.

PMID- 24114716
TI  - Sluggish cognitive tempo is associated with academic functioning and
      internalizing symptoms in college students with and without attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVES: The purposes of the present studies were to (a) examine the factor
      structure of sluggish cognitive tempo (SCT) and attention-deficit/hyperactivity
      disorder (ADHD) in college students and (b) examine the associations between SCT
      and academic functioning and internalizing symptoms in college students with and
      without ADHD. METHOD: In Study 1, a confirmatory factor analysis of the Barkley
      Adult ADHD Rating Scale-IV (BAARS-IV) was conducted in a sample of 768 college
      students (aged 17-34 years, 68% female). In Study 2, we examined the relation of
      SCT to academic functioning and internalizing symptoms in a sample of 72 college
      students rigorously diagnosed with ADHD (aged 17-35 years, 44% female). RESULTS:
      Study 1 results supported the factor structure of the BAARS-IV, with the optimal
      model comprising 4 correlated but distinct factors: SCT, Inattention,
      Hyperactivity, and Impulsivity. After controlling for correlated demographic
      variables and ADHD symptoms, SCT was significantly related to academic impairment
      (including grade point average), anxiety, and depression. In Study 2, SCT again
      contributed unique variance to internalizing symptoms and academic impairment
      after controlling for correlated participant characteristics (i.e., sex, age,
      race, parent education level, family income, ADHD medication use, and mental
      health service utilization) and ADHD symptom severity. CONCLUSIONS: These results
      fill an important gap in the literature by (a) confirming SCT to be distinct from
      ADHD in emerging adulthood, (b) demonstrating SCT to be strongly linked to
      college student adjustment, and (c) providing support for the hypothesis that SCT
      is associated with psychosocial functioning in both individuals with and without
      ADHD.

PMID- 24114718
TI  - Effects of a cognitive-behaviorally based physical activity treatment for 4- and
      5-year-old children attending US preschools.
AB  - BACKGROUND: Inadequate volumes of physical activity may be associated with the
      increases in inappropriately high weight in children of 5 years of age and
      younger. Preschools have typically lacked sufficient time in daily physical
      activity. PURPOSE: A preschool-administered physical activity treatment based on
      social cognitive and self-efficacy theory (Start For Life) was tested for its
      association with increased physical activity and reduced body mass index (BMI).
      METHODS: Data from accelerometer and BMI assessments over a 9-month preschool
      year (18 treatment and 8 control classes of 17 to 20 children each; mean age =
      4.4 years) were used to contrast the behaviorally based treatment of 30 min per
      day with a usual care condition of the same duration. The sample was primarily
      African-American. Preschool teachers administered all processes. RESULTS: The
      Start For Life treatment was associated with a significantly greater percentage
      of the preschool day in moderate-to-vigorous and vigorous physical activity
      (approximately 30 min per week more), with sedentary time unaffected. The
      treatment was also associated with a significant reduction in BMI, with effect
      sizes greatest in overweight and obese children. CONCLUSIONS: Although results
      were positive in contrast to usual care and other related interventions, the
      specific sample requires that the Start For Life treatment undergo sufficient
      replication to increase confidence in generalizability of the findings to others.
      Although reduction in sedentary time may require a different strategy, the
      practical application of the present treatment suggests possibilities for
      addressing overweight through increasing moderate-to-vigorous physical activity
      in preschool settings.

PMID- 24114717
TI  - In vivo beta-adrenergic receptor responsiveness: ethnic differences in the
      relationship with symptoms of depression and fatigue.
AB  - BACKGROUND: Depressive symptoms and fatigue frequently overlap in clinical
      samples and the general population. The link of depressive symptoms and fatigue
      with increased risk of cardiovascular disease has been partly explained by shared
      biological mechanisms including sympathetic overactivity. Prolonged sympathetic
      overactivity downregulates the responsiveness of the beta-adrenergic receptor
      (beta-AR), a receptor that mediates several end-organ sympathetic responses.
      PURPOSE: The authors studied whether depression and fatigue are related to
      reduced beta-AR responsiveness within the human body (in vivo) in an ethnically
      diverse sample of African and Caucasian Americans. METHODS: The chronotropic25
      dose (CD25) was used to determine in vivo beta-AR responsiveness in 93 healthy
      participants. Psychometric measures included the Center of Epidemiological
      Studies-Depression Scale and the Multidimensional Fatigue Symptom Inventory.
      RESULTS: Hierarchical regression analyses (adjusted for age, gender, body mass
      index, blood pressure, smoking, and ethnicity) revealed that mental fatigue was
      significantly related to reduced beta-AR responsiveness (i.e., higher CD25
      values) in the whole sample. Moderation analyses indicated significant ethnicity
      * depression/fatigue interactions. Depressive symptoms, total fatigue, emotional
      fatigue, mental fatigue, and physical fatigue were related to reduced beta-AR
      responsiveness in Caucasian American but not in African Americans. CONCLUSIONS:
      Our findings suggest that symptoms of depression and fatigue are related to
      decreased in vivo beta-AR responsiveness in Caucasian Americans. The lack of this
      association in African Americans highlights the importance for considering
      ethnicity as a potential moderator in research focusing on associations between
      psychological variables and cardiovascular function.

PMID- 24114719
TI  - Single-cell based high-throughput sequencing of full-length immunoglobulin heavy
      and light chain genes.
AB  - Single-cell PCR and sequencing of full-length Ig heavy (Igh) and Igk and Igl
      light chain genes is a powerful tool to measure the diversity of antibody
      repertoires and allows the functional assessment of B-cell responses through
      direct Ig gene cloning and the generation of recombinant mAbs. However, the
      current methodology is not high-throughput compatible. Here we developed a two
      dimensional bar-coded primer matrix to combine Igh and Igk/Igl chain gene single
      cell PCR with next-generation sequencing for the parallel analysis of the
      antibody repertoire of over 46 000 individual B cells. Our approach provides full
      length Igh and corresponding Igk/Igl chain gene-sequence information and permits
      the accurate correction of sequencing errors by consensus building. The use of
      indexed cell sorting for the isolation of single B cells enables the integration
      of flow cytometry and Ig gene sequence information. The strategy is fully
      compatible with established protocols for direct antibody gene cloning and
      expression and therefore advances over previously described high-throughput
      approaches to assess antibody repertoires at the single-cell level. 

PMID- 24114720
TI  - Assessment for retreatment (ART) score for repeated transarterial
      chemoembolization in patients with hepatocellular carcinoma.

PMID- 24114721
TI  - Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to
      mesenchymal transition in peritoneal metastasis.
AB  - Peritoneal dissemination is a frequent metastatic route for cancers of the ovary
      and gastrointestinal tract. Tumour cells metastasize by attaching to and invading
      through the mesothelial cell (MC) monolayer that lines the peritoneal cavity.
      Metastases are influenced by carcinoma-associated fibroblasts (CAFs), a cell
      population that derives from different sources. Hence, we investigated whether
      MCs, through mesothelial-mesenchymal transition (MMT), were a source of CAFs
      during peritoneal carcinomatosis and whether MMT affected the adhesion and
      invasion of tumour cells. Biopsies from patients with peritoneal dissemination
      revealed the presence of myofibroblasts expressing mesothelial markers in the
      proximity of carcinoma implants. Prominent new vessel formation was observed in
      the peritoneal areas harbouring tumour cells when compared with tumour-free
      regions. The use of a mouse model of peritoneal dissemination confirmed the
      myofibroblast conversion of MCs and the increase in angiogenesis at places of
      tumour implants. Treatment of omentum MCs with conditioned media from carcinoma
      cell cultures resulted in phenotype changes reminiscent of MMT. Adhesion
      experiments demonstrated that MMT enhanced the binding of cancer cells to MCs in
      a beta1-integrin-dependent manner. Scanning electron microscopy imaging showed
      that the enhanced adhesion was mostly due to increased cell-cell interaction and
      not to a mere matrix exposure. Invasion assays suggested a reciprocal stimulation
      of the invasive capacity of tumour cells and MCs. Our results demonstrate that
      CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest
      that MMT renders the peritoneum more receptive for tumour cell
      attachment/invasion and contributes to secondary tumour growth by promoting its
      vascularization.

PMID- 24114722
TI  - Residual viremia in patients on antiretroviral therapy incorporating nevirapine
      is not associated with the gag-specific cellular immune response.
AB  - To determine whether residual plasma viremia in HIV(+) patients on nevirapine
      including antiretroviral therapy (ART) is related to anti-HIV cellular immune
      responses, a case-control study was conducted comparing residual viremia in
      patients with detectable and undetectable Gag-specific T-cell responses. Gag
      specific responses were measured by IFN-gamma ELISpot. Residual viremia was
      determined at two consecutive hospital visits by an ultra-sensitive technique
      with a detection limit of 2 copies/ml. Median residual viremia was not different
      in patients with a positive Gag-specific ELISpot (n = 25) compared to those with
      a negative Gag-specific ELISpot (n = 30, P = 0.91). Ten of 25 (40%) patients with
      consistent detectable residual viremia and 4 of 12 (33%) patients with
      consistently undetectable residual viremia had a positive Gag-specific ELISpot.
      Undetectable residual viremia was associated with the duration of ART including
      nevirapine (P < 0.05), but not with the Gag-specific ELISpot response. Gag
      specific CTL in patients on ART therefore appear to have no impact on the virus
      producing cells that are responsible for residual viremia during ART.

PMID- 24114723
TI  - Autofluorescence properties of murine embryonic stem cells during spontaneous
      differentiation phases.
AB  - BACKGROUND AND OBJECTIVE: The autofluorescence (AF) analysis allows in vivo, real
      time assessment of cell functional activities, depending on the presence of
      biomolecules strictly involved in metabolic reactions and acting as endogenous
      fluorophores. Pluripotent stem cells during differentiation are known to undergo
      changes in their morphofunctional properties, with particular reference to
      bioenergetic metabolic signatures involving endogenous fluorophores such as
      NAD(P)H, flavins, lipofuscin-like lipopigments. Since the development of
      regenerative therapies based on pluripotent cells requires a careful monitoring
      of the successful maturation into the desired phenotype, aim of our work is to
      evaluate the AF potential to assess the differentiation phases in a murine stem
      cell model. STUDY DESIGN/MATERIALS AND METHODS: Mouse embryonic stem cells (ESCs)
      maintained with and without leukemia inhibitory factor (LIF), embryoid bodies
      (EBs), and EB-derived cells undergoing spontaneous differentiation toward the
      hematopoietic lineage have been used as a sample models. Cell AF properties have
      been characterized upon 366-nm excitation, under living conditions and in the
      absence of exogenous markers. Imaging, microspectrofluorometric techniques, and
      spectral fitting analysis based on the spectral parameters of each endogenous
      fluorophore have been applied to estimate their contribution to the whole cell AF
      emission spectra. Specific cytochemical labeling has been performed to validate
      AF data. RESULTS: Depending on the differentiation phases, cells undergo changes
      in morphology, AF distribution patterns, and AF emission spectral profiles. These
      latter reflect variations in the single endogenous fluorophore contribution to
      the overall emission. The coenzyme NAD(P)H accounts for up to 80% of the whole
      spectral area. The free form prevails on the bound one, and their changes have
      been investigated in terms of NAD(P)Hbound/free and redox ratios. These values
      vary in agreement with a slow metabolic activity and prevailing glycolytic
      metabolism in the undifferentiated HM1 cells, an increased metabolic activity
      still relying on glycolysis during the early differentiation phases, and an
      increased oxidative phosphorylation in EB and hematopoietic precursor cells.
      Lipofuscin-like lipopigments decrease following differentiation, and porphyrins
      contributing for less than 5%, prevail in the more actively differentiating
      cells. These results reflect the shift between anaerobic and aerobic respiration
      following differentiation, consistently with a decreased autophagy of cell
      organelles (i.e., mitochondria, as a strategy reported in the literature to keep
      the undifferentiated homeostasis state), higher mitochondrial activity with more
      numerous NADH binding sites and synthesis of heme as prosthetic group of
      proteins, that is, cytochromes. CONCLUSIONS: These data open promising
      perspectives for the monitoring of stem cells differentiation under living
      conditions without labeling with exogenous agents (inducing perturbations when
      used in vivo), or immunomarkers not always available for veterinary and
      zootechnics, by exploiting endogenous fluorophores as intrinsic biomarkers of
      cell morphofunctional changes.

PMID- 24114724
TI  - Characteristics and factors associated with the clinical forms of lipoatrophy
      during highly active antiretroviral therapy in Ouagadougou, Burkina Faso.
AB  - BACKGROUND: We aimed to study the factors associated with clinical forms of
      lipoatrophy in patients receiving highly active antiretroviral therapy (HAART) in
      Yalgado Ouedraogo Teaching Hospital, Ouagadougou, Burkina Faso. METHODS: This
      cross-sectional review from March 10 to November 10, 2011, included a
      nonprobability sample of HIV-infected adults receiving antiretroviral (ARV)
      medications for at least 6 months and monitored in the internal medicine
      department. The diagnosis of lipoatrophy was clinical. RESULTS: Three hundred
      patients were included. The sex ratio was 0.4 and the mean age was 42.1 +/- 8.5
      years. The mean duration of HAART was 73.2 +/- 30.9 months. In all, 97 (32.3%)
      patients had lipoatrophy: 75 (25%) isolated and 22 (7.3%) mixed syndrome. Facial
      lipoatrophy was frequent (61.8%). Isolated lipoatrophy was associated with male
      sex (P = .002) and body mass index <=25 (P < .05). Mixed syndrome was associated
      with female sex (P = .002), age >42 years (P < .05), physical activity (P =
      .003), smoking (P = .001), stavudine (d4T; P = .0001), or protease inhibitors (P
      = .01). CONCLUSION: Prevention of lipoatrophy associated with HAART requires the
      exclusion of modifiable risk factors that we identified.

PMID- 24114725
TI  - Evaluation of parent-child pairs on antiretroviral therapy in separate adult and
      pediatric clinics.
AB  - In Africa, HIV infection is considered a family disease. A retrospective cohort
      analysis was performed to describe the characteristics and outcome in 35 parent
      child pairs taking antiretroviral therapy (ART) in separate adult and pediatric
      HIV clinics. In 26 pairs, ART was first initiated in children. Baseline median
      CD4 count was 122/mm(3) in adults and 376/mm(3) in children. World Health
      Organization stage 3 or 4 disease affected 49% of adults and 83% of children. In
      all, 3 parents and 1 child died. Hospitalization, poor adherence, missed
      appointments, or regimen change affected >50% of pairs on ART. Following
      tuberculosis diagnosis in their parents, 2 of the 5 children were not
      investigated. By week 104, 29 (83%) pairs remained on ART, and 69% of patients on
      ART were virologically suppressed. Parent-child pairs with advanced HIV infection
      had good outcomes when cared for in separate clinics. Establishing lines of
      communication between clinics is important. Family-centered services may provide
      more integrated care. 

PMID- 24114726
TI  - The effect of depressive symptoms and CD4 count on adherence to highly active
      antiretroviral therapy in sub-Saharan Africa.
AB  - BACKGROUND: Studies have identified several programmatic and nonprogrammatic
      indicators that affect adherence to highly active antiretroviral therapy (HAART).
      Depression has been shown to impact adherence to HAART. This cross-sectional
      analysis of data collected from Nigeria, Uganda, Zambia, and Tanzania in 2008
      examined the relationship between levels of depressive symptoms, clinical
      progression, and adherence to HAART. METHODS: A multinational, multicenter,
      observational, retrospective cross-sectional evaluation of a population of focus
      comprised randomly selected patients on HAART. The dependent variable was
      adherence to HAART. The primary variable of interest to be assessed was patients'
      level of depressive symptom score. A multivariable logistic regression model was
      used to examine the relationship between explanatory variables and adherence to
      HAART. RESULTS: A total of 2344 patients were recruited for adherence survey.
      About 70% of the study sample reported having some level of depression. Logistic
      regression results show that patients who reported, respectively, low, moderate,
      and high levels of depressive symptoms are 35% (P < .001), 56% (P < .001), and
      64% (P < .001) less likely to adhere to HAART than those who reported having no
      depressive symptoms. At multivariate analysis, adherence to HAART was
      independently associated with the levels of depressive symptoms, older age, CD4
      count >200 cells/mm3, Truvada (tenofovir [TDF]/emtricitabine [FTC])-based
      regimens, good knowledge about HAART, and longer period on therapy. CONCLUSIONS:
      These results indicate that mental health and clinical parameters are significant
      factors in determining patients' adherence to their HAART, which need to be more
      aggressively addressed as a critical component of care and treatment support.

PMID- 24114727
TI  - Frontal sinus drillout (modified Lothrop procedure): long-term results in 204
      patients.
AB  - OBJECTIVES/HYPOTHESIS: To determine the long-term results of frontal sinus
      drillout (also known as modified Lothrop procedure) for the treatment of advanced
      frontal sinus disease. STUDY DESIGN: Retrospective review. METHODS: The records
      of patients who underwent frontal sinus drillout by a single surgeon at an
      academic medical center from June 1995 through November 2011 were reviewed.
      Patient demographics and perioperative clinical findings were analyzed for their
      impact on surgical outcome. Failure was defined as restenosis of the frontal
      drainage pathways, necessitating additional frontal sinus surgery. RESULTS: A
      total of 204 patients underwent frontal drillout surgery (143 bilateral
      procedures) over the 16-year period. Mean follow-up was 10.2 years (range 0.9-17
      years). Symptomatic re-obstruction of the frontal sinus requiring revision
      surgery occurred in 61 (29.9%) patients. Drillouts performed for a diagnosis of
      mucocele or tumor had significantly higher failure rate (38.9%, odds ratio [OR] =
      2.9, P = 0.022 and 58.3%, OR = 5.3, P = 0.020, respectively). The majority of
      surgical failures (61%) occurred within 2 years of surgery, but delayed failures
      were observed up to 12 years after drillout. Clinical outcome did not correlate
      with a history of smoking, asthma, nasal allergy, aspirin sensitivity, prior
      sinus surgery, nasal polyposis, or the presence of eosinophilic mucin.
      CONCLUSION: For the majority of patients who undergo frontal sinus drillout,
      patency of the frontal sinus outflow tract appears to be maintained for more than
      a decade; nevertheless, almost one-third of patients who undergo this procedure
      will ultimately require additional frontal sinus surgery.

PMID- 24114728
TI  - A novel fabrication technique to minimize poly(dimethylsiloxane)-microchannels
      deformation under high-pressure operation.
AB  - PDMS is one of the most common materials used for the flow delivery in the
      microfluidics chips, since it is clear, inert, nontoxic, and nonflammable. Its
      inexpensiveness, straightforward fabrication, and biological compatibility have
      made it a favorite material in the exploratory stages of the bio-microfluidic
      devices. If small footprint assays want to be performed while keeping the
      throughput, high pressure-rated channels should be used, but PDMS flexibility
      causes an important issue since it can generate a large variation of microchannel
      geometry. In this work, a novel fabrication technique based on the prevention of
      PDMS deformation is developed. A photo-sensible thiolene resin (Norland Optical
      Adhesive 63, NOA 63) is used to create a rigid coating layer over the stiff PDMS
      micropillar array, which significantly reduces the pressure-induced shape
      changes. This method uses the exact same soft lithography manufacturing
      equipment. The verification of the presented technique was investigated
      experimentally and numerically and the manufactured samples showed a deformation
      70% lower than PDMS conventional samples. 

PMID- 24114729
TI  - The effects of presession attention on tacting.
AB  - This study examined the effects of presession attention on tacting. Presession
      intervals of deprivation and satiation of attention were followed by a
      progressive-ratio assessment in which the number of tacts was measured. For 2
      participants, deprivation resulted in increased tacting compared to satiation.
      The 3rd participant showed no differential responding. These results suggest that
      antecedent-based interventions could increase the efficiency of tact training. 

PMID- 24114730
TI  - Preparing clinical pharmacy scientists for careers in clinical/translational
      research: can we meet the challenge?: ACCP Research Affairs Committee Commentary.
AB  - Developing clinical pharmacists' research skills and their ability to compete for
      extramural funding is an important component of the American College of Clinical
      Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating
      the new knowledge used to guide patient pharmacotherapy. Given the recent
      emphasis on clinical/translational research at the National Institutes of Health
      (NIH) and the key role of drug therapy in the management of many diseases, there
      is an unprecedented opportunity for the profession to contribute to this
      enterprise. A crucial question facing the profession is whether we can generate
      enough appropriately trained scientists to take advantage of these opportunities
      to generate the new knowledge to advance drug therapy. Since the 2009 publication
      of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree
      (as opposed to fellowship training) as the optimal method for preparing
      pharmacists as clinical/translational scientists, significant changes have
      occurred in the economic, professional, political, and research environments. As
      a result, the 2012 ACCP Research Affairs Committee was charged with reexamining
      the college's position on training clinical pharmacy scientists in the context of
      these substantial environmental changes. In this commentary, the potential impact
      of these changes on opportunities for pharmacists in clinical/translational
      research are discussed as are strategies for ACCP, colleges of pharmacy, and the
      profession to increase the number and impact of clinical pharmacy scientists.
      Failure of our profession to take advantage of these opportunities risks our
      ability to contribute substantively to the biomedical research enterprise and
      ultimately improve the pharmacotherapy of our patients. 

PMID- 24114731
TI  - Reply to clinical predictors of survival in men with castration-resistant
      prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal
      disease.

PMID- 24114732
TI  - A rapid test for avian influenza detects swine influenza virus.

PMID- 24114733
TI  - A retrospective study of pyometra at five RSPCA hospitals in the UK: 1728 cases
      from 2006 to 2011.
AB  - A retrospective cross-sectional study was used to analyse pyometra cases at five
      RSPCA Animal Hospitals across the UK from 2006 to 2011. A total of 1728 cases of
      pyometra were recovered from a female dog outpatient caseload of 78,469 animals,
      giving a total prevalence of 2.2 per cent over the study period. There was an
      annual increase in the incidence of pyometra within the population, while
      elective ovariohysterectomy caseload has declined. There were variations in breed
      and age at presentation. Bullmastiffs (P<0.0001), golden retrievers (P=0.001) and
      dogue de Bordeaux (P=0.008) were over-represented in the pyometra population when
      compared with the female dog outpatient caseload. Mean age at presentation was
      7.7 years. Some breeds presented at a significantly lower age, including dogue de
      Bordeaux (mean age 3.3 years) and bullmastiffs (mean age 5.4 years), while others
      presented as older dogs, including Yorkshire terriers (mean age 9.4 years) and
      border collies (mean age 10.3 years). Surgical mortality rate at the Greater
      Manchester Animal Hospital was 3.2 per cent. Pyometra is of significant welfare
      concern, and also has cost implications, particularly in charity practice. These
      results serve to highlight this condition so that future change in charity
      practice caseload can be anticipated and strategies can be directed to improve
      animal welfare. 

PMID- 24114734
TI  - Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a
      randomised, controlled, double-blinded trial.
AB  - Antihistaminic drugs are commonly used as symptomatic therapy of atopic
      dermatitis in dogs. Unfortunately, their clinical benefit is largely
      unsubstantiated. In a double-blinded, placebo-controlled, cross-over trial, the
      influence of dimetinden and of a combination of chlorpheniramine and hydroxyzine
      on pruritus and lesions was evaluated in 19 dogs. They were treated with either
      product or a placebo orally for 14 days, each time followed by a 14-day washout
      period. Before and after each period, the dogs were examined and the Canine
      Atopic Dermatitis Extent and Severity Index (CADESI) determined by a clinician,
      and the pruritus and general condition by the owner. Dimetinden improved the
      pruritus significantly (P=0.014) but not the CADESI (P=0.087), the combination of
      hydroxyzine and chlorpheniramine improved the CADESI (P=0.049) and pruritus
      (P=0.05) significantly. Ten of 17 dogs improved by more than 25 per cent in
      pruritus with the combination of hydroxyzine and chlorpheniramine, 12 of 18 with
      dimetindenmaleate and only 2 of 19 with placebo. Antihistamines can help to
      reduce pruritus in atopic dogs, but in most cases, the improvement is limited and
      additional treatment may be needed. 

PMID- 24114735
TI  - Additive effect of the AZGP1, PIP, S100A8 and UBE2C molecular biomarkers improves
      outcome prediction in breast carcinoma.
AB  - The deregulation of key cellular pathways is fundamental for the survival and
      expansion of neoplastic cells, which in turn can have a detrimental effect on
      patient outcome. To develop effective individualized cancer therapies, we need to
      have a better understanding of which cellular pathways are perturbed in a
      genetically defined subgroup of patients. Here, we validate the prognostic value
      of a 13-marker signature in independent gene expression microarray datasets (n =
      1,141) and immunohistochemistry with full-faced FFPE samples (n = 71). The
      predictive performance of individual markers and panels containing multiple
      markers was assessed using Cox regression analysis. In the external gene
      expression dataset, six of the 13 genes (AZGP1, NME5, S100A8, SCUBE2, STC2 and
      UBE2C) retained their prognostic potential and were significantly associated with
      disease-free survival (p < 0.001). Protein analyses refined the signature to a
      four-marker panel [AZGP1, Prolactin-inducible protein (PIP), S100A8 and UBE2C]
      significantly correlated with cycling, high grade tumors and lower disease
      specific survival rates. AZGP1 and PIP were found in significantly lower levels
      in invasive breast tissue as compared with adjacent normal tissue, whereas
      elevated levels of S100A8 and UBE2C were observed. A predictive model containing
      the four-marker panel in conjunction with established clinical variables
      outperformed a model containing the clinical variables alone. Our findings
      suggest that deregulated AZGP1, PIP, S100A8 and UBE2C are critical for the
      aggressive breast cancer phenotype, which may be useful as novel therapeutic
      targets for drug development to complement established clinical variables. 

PMID- 24114736
TI  - Decreasing rates of invasive candidiasis in pediatric hospitals across the United
      States.
AB  - Rates of invasive candidiasis (IC) in children between 2003 and 2011 were
      evaluated in a retrospective cross-sectional analysis. The rate of IC decreased
      72% (P < .001) overall and 91% in neonates (P < .001). Improving infection
      control efforts is thought to be a contributing factor for this decrease. 

PMID- 24114737
TI  - Effect of fish oil and linseed supplementation on the protein composition of milk
      from cows with different beta-lactoglobulin phenotypes.
AB  - BACKGROUND: The objective of this study was to determine the impact of fish oil
      and linseed (FOL) supplements on the protein fraction levels of milk from cows
      with different phenotypes of beta-lactoglobulin. RESULTS: After 21 days of
      supplementation the study showed significantly higher concentrations of whey
      proteins, especially lysozyme (144% increase) and lactoferrin (45.5% increase),
      compared with milk from control cows (total mixed ration with no supplemented
      FOL). A reverse trend was demonstrated for casein, casein index and casein number
      (lower level). The most favourable change (higher level), in terms of
      lactoferrin, alpha-lactalbumin and bovine serum albumin contents in milk, was
      recorded in cows with the BB variant of beta-lactoglobulin. The highest level of
      lysozyme was recorded in the milk of cows with the AB variant of beta
      lactoglobulin. CONCLUSION: The combined supplementation of fish oil and linseed
      had a positive impact on whey proteins in cow's milk. In addition, the phenotype
      of beta-lactoglobulin also played a role in milk protein composition. There is
      therefore a clear indication that nutritional experiments should take into
      account not only food supplements but also the genetic variants of beta
      lactoglobulin.

PMID- 24114738
TI  - Eliciting preferences for prioritizing treatment of rare diseases: the role of
      opportunity costs and framing effects.
AB  - BACKGROUND: Understanding societal preferences regarding resource allocation in
      the health sector has gained importance as countries increasingly base
      reimbursement decisions on economic evaluations. Preference elicitation using
      surveys, a common practice in the health sector, is subject to a range of framing
      effects. OBJECTIVE: This research investigates the importance of (theoretically
      relevant) opportunity costs and (theoretically irrelevant) framing effects on
      stated preferences for prioritizing treatment of rare (orphan) diseases. METHODS:
      We elicited preferences from Norwegians, aged 40-67, using simple trade-off
      exercises. Respondents were randomised to different opportunity costs of the rare
      disease or to different framings of the trade-off exercises. RESULTS: Respondents
      were quite sensitive to the visual presentation of the choice problem, and, to a
      lesser extent, to focusing and labelling effects. Elicited preferences varied
      little in response to large changes in opportunity costs, suggesting scope
      insensitivity among respondents. CONCLUSIONS: Preferences for prioritizing
      treatment of rare diseases elicited using trade-off exercises are insensitive to
      (theoretically relevant) opportunity costs, but sensitive to (theoretically
      irrelevant) framing effects.

PMID- 24114739
TI  - Vemurafenib for the treatment of locally advanced or metastatic BRAF V600
      mutation-positive malignant melanoma: a NICE single technology appraisal.
AB  - Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally
      advanced or metastatic BRAF V600-mutation positive malignant melanoma. The
      manufacturer of vemurafenib, Roche Products Limited, was invited by the National
      Institute for Health and Care Excellence (NICE) to submit evidence of the drug's
      clinical- and cost-effectiveness for its licenced indication, to inform the
      Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and
      Implementation Group (LRiG) at the University of Liverpool was commissioned to
      act as the Evidence Review Group (ERG) for this appraisal. This article
      summarises the ERG's review of the evidence submitted by the manufacturer and
      also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG
      reviewed the clinical- and cost-effectiveness evidence in accordance with the
      decision problem defined by NICE. The ERG's analysis of the submitted economic
      model assessed the appropriateness of the approach taken by the manufacturer in
      modelling the decision problem. It also included an assessment of the reliability
      of model implementation and the extent of conformity to published standards and
      prevailing norms of practice within the health economics modelling community.
      Particular attention was paid to issues likely to impact substantially on the
      base-case cost-effectiveness results. The clinical evidence was derived from BRIM
      3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national,
      phase III, randomised controlled trial (RCT). Clinical outcome results from the
      October 2011 data cut showed that median overall survival for patients treated
      with vemurafenib was 13.2 months compared with 9.6 months for those treated with
      dacarbazine. The ERG's main concern with the trial was the potential for
      confounding because of the early introduction of the crossover from the
      comparator drug to vemurafenib or another BRAF inhibitor. The submitted
      incremental cost-effectiveness ratio (ICER) was considered above the NICE
      threshold, even when end-of-life criteria were taken into account. The ERG
      questioned the submitted economic model on a number of grounds, particularly the
      approach used to project trial results. After the ERG had made appropriate
      corrections to the model and employed an alternative form of projective
      modelling, the ICER per quality-adjusted life year more than doubled. Additional
      evidence was submitted by the manufacturer for consideration at a second AC
      meeting and at their third meeting the AC concluded that vemurafenib could be
      recommended as first-line maintenance treatment for patients with locally
      advanced or metastatic BRAF V600 mutation-positive malignant melanoma. 

PMID- 24114740
TI  - Palliative care communication: linking patients' prognoses, values, and goals of
      care.
AB  - Prognostic communication is a primary component of goals of care conversations in
      palliative care (PC) practice. Little is known about these conversations in the
      natural setting. This study's aim was to describe the processes of prognostic
      communication in PC goals of care consultations. Using line-by-line qualitative
      analysis, we examined prognostic conversation in 66 audio-taped PC consultations.
      We identified five processes by which clinicians link prognoses, values, and
      goals of care: (1) signposting the crossroads; (2) closing off a goal; (3)
      clarifying current path; (4) linking paths and patients' values; and (5) choosing
      among paths. The findings add to our understanding of PC consultation by
      describing how prognoses link with patients' values and choices in goals of care
      conversations.

PMID- 24114741
TI  - Towards an integrated in vitro strategy for estrogenicity testing.
AB  - In order to define an in vitro integrated testing strategy (ITS) for
      estrogenicity, a set of 23 reference compounds representing diverse chemical
      classes were tested in a series of in vitro assays including proliferation and
      reporter gene assays. Outcomes of these assays were combined with published
      results for estrogen receptor (ER) binding assays and the OECD validated BG1Luc
      ER transcriptional activation (TA) assay and compared with the outcomes of the in
      vivo uterotrophic assay to investigate which assays most accurately predict the
      in vivo uterotrophic effect and to identify discrepancies between the in vitro
      assays and the in vivo uterotrophic assay. All in vitro assays used revealed a
      reasonable to good correlation (R(2)  = 0.62-0.87) with the in vivo uterotrophic
      assay but the combination of the yeast estrogen bioassay with the U2OS ERalpha
      CALUX assay seems most promising for an ITS for in vitro estrogenicity testing.
      The main outliers identified when correlating data from the different in vitro
      assays and the in vivo uterotrophic assay were 4-hydroxytamoxifen, testosterone
      and to a lesser extent apigenin, tamoxifen and kepone. Based on the modes of
      action possibly underlying these discrepancies it becomes evident that to further
      improve the ITS and ultimately replace animal testing for (anti-)estrogenic
      effects, the selected bioassays have to be combined with other types of in vitro
      assays, including for instance in vitro models for digestion, bioavailability and
      metabolism of the compounds under investigation.

PMID- 24114742
TI  - Drug shortages in Canadian anesthesia: a national survey.

PMID- 24114743
TI  - Hemodynamic instability and fluid responsiveness.

PMID- 24114745
TI  - Reply: To PMID 23316013.

PMID- 24114744
TI  - Longer length BahaTM abutments decrease wound complications and revision surgery.
AB  - OBJECTIVES/HYPOTHESIS: To study the complication rates of skin overgrowth,
      infection, and the need for revision surgery in longer length BahaTM abutments.
      STUDY DESIGN: Prospective observational cohort study compared with a
      retrospective historical control. METHODS: After the University of Nebraska
      Medical Center (UNMC) Institutional Review Board approval was obtained, data was
      collected from a prospective 8.5-mm abutment study group of 21 subjects with
      informed consent from October 2011 through October 2012, and was compared to a
      retrospective 5.5-mm abutment historical cohort of 23 patients who had undergone
      BahaTM by the same surgeon from May 2010 to October 2011. Patient demographics,
      body mass index (BMI), smoking status, and wound complications (skin overgrowth,
      infection, the need for revision surgery) were statistically investigated and
      compared between the groups. RESULTS: Forty-four patients were studied. The
      groups were similar in smoking status, diabetes, and a female preponderance. The
      8.5-mm abutment group was older (P = 0.012). The average BMI for both groups was
      classified as overweight and nearly obese (BMI 28.8). Rates of infection, skin
      overgrowth, and the need for revision surgery related to wound complications were
      significantly decreased in the longer 8.5-mm abutment group (P = 0.020, P =
      0.012, P = 0.007, respectively). BMI did not correlate with decreased infection,
      skin overgrowth, and the need for revision surgery based on abutment length as
      hypothesized (P = 0.214, P = 0.206, P = 0.408). CONCLUSIONS: The 8.5-mm abutment
      lends to decreased complications postoperatively, including infection, skin
      overgrowth, and the need for revision surgery. LEVEL OF EVIDENCE: 3b.

PMID- 24114746
TI  - Attention training reduces intrusive thoughts cued by a narrative of stressful
      life events: a controlled study.
AB  - OBJECTIVES: Intrusive thoughts are common distressing symptoms that occur after
      exposure to stressful life events. This study tested the idea, based on
      metacognitive theory, that such intrusions may be ameliorated by the Attention
      Training Technique (ATT; Wells,). METHOD: Participants who reported distressing
      intrusions were randomly allocated to two sessions of ATT (plus homework) or a
      filler task and were exposed to a narrative recording of their traumatic
      experience before and after the intervention. Frequencies of intrusions occurring
      during the narrative were measured. A measure of self-reported attention
      flexibility was also examined. RESULTS: Participants in the ATT condition showed
      a significant reduction in intrusion frequency and an increase in attention
      flexibility compared with the control group. ATT was associated with a 3.4 times
      greater reduction in the incidence of intrusions. CONCLUSIONS: ATT may be an
      effective technique for reducing symptoms of stress exposure, reducing the
      incidence of intrusions when exposed to stimuli associated with stressful events.

PMID- 24114747
TI  - 2D TCR-pMHC-CD8 kinetics determines T-cell responses in a self-antigen-specific
      TCR system.
AB  - Two-dimensional (2D) kinetic analysis directly measures molecular interactions at
      cell-cell junctions, thereby incorporating inherent cellular effects. By
      comparison, three-dimensional (3D) analysis probes the intrinsic physical
      chemistry of interacting molecules isolated from the cell. To understand how T
      cell tumor reactivity relates to 2D and 3D binding parameters and to directly
      compare them, we performed kinetic analyses of a panel of human T-cell receptors
      (TCRs) interacting with a melanoma self-antigen peptide (gp100209 -217 ) bound to
      peptide-major histocompatibility complex in the absence and presence of co
      receptor CD8. We found that while 3D parameters are inadequate to predict T-cell
      function, 2D parameters (that do not correlate with their 3D counterparts) show a
      far broader dynamic range and significantly improved correlation with T-cell
      function. Thus, our data support the general notion that 2D parameters of TCR
      peptide-major histocompatibility complex-CD8 interactions determine T-cell
      responsiveness and suggest a potential 2D-based strategy to screen TCRs for tumor
      immunotherapy. 

PMID- 24114748
TI  - Free rehabilitation is safe after isolated meniscus repair: a prospective
      randomized trial comparing free with restricted rehabilitation regimens.
AB  - BACKGROUND: The optimal rehabilitation program after meniscus repair has not been
      established. Numerous regimens have been suggested as beneficial for meniscus
      healing, but no controlled trials exist in the literature. HYPOTHESIS: The
      purpose of this prospective randomized trial was to investigate outcome with a
      free or a restricted rehabilitation regimen after isolated meniscus repair. The
      hypothesis was that free rehabilitation would result in increased failure of
      meniscus healing. STUDY DESIGN: Randomized controlled clinical trial; Level of
      evidence, 1. METHODS: A total of 60 patients were included in this study within 2
      to 3 days after meniscus repair. No patients with concomitant ligament
      reconstruction or cartilage repair surgery were included. Meniscus repair was
      performed with the all-inside technique; only vertical meniscus lesions close to
      the capsule were repaired. Patients were randomized to free (n = 32) or
      restricted (n = 28) rehabilitation. Free rehabilitation consisted of 2 weeks
      (range of motion [ROM], 0 degrees -90 degrees , no brace) and touch
      weightbearing, with unrestricted activity and free ROM allowed thereafter.
      Restricted rehabilitation consisted of 6 weeks of hinged brace use with a gradual
      increase ROM to 90 degrees  and only touch weightbearing during the 6 weeks.
      Patients were seen for follow-up at 3 months, 1 year, and 2 years. Those patients
      with joint line pain at the 3-month follow-up underwent MRI scanning to evaluate
      meniscus healing; a subsequent arthroscopy was performed for final evaluation
      meniscus healing if the MRI indicated lack of meniscus healing. At follow-up, the
      Knee Osteoarthritis Outcome Score (KOOS), Tegner function score, pain assessment,
      and patient satisfaction were used to evaluate outcomes. RESULTS: Eleven patients
      were lost to follow-up. Repeat arthroscopy in patients with persistent symptoms
      demonstrated partial healing or lack of healing in 28% and 36% of patients in the
      free and the restricted rehabilitation groups, respectively (P = .53,
      nonsignificant). The KOOS and Tegner function scores were similar between groups
      at all follow-up times, as was patient satisfaction. Patients who underwent
      subsequent partial meniscectomy because of meniscus repair failure had lower KOOS
      score and Tegner function score than did patients without repair failure.
      CONCLUSION: Free rehabilitation after meniscus repair is safe and does not entail
      increased failure rates compared with restricted rehabilitation. Subjective and
      functional outcomes at 1- and 2-year follow-up were not affected by
      rehabilitation regimen. Clinical outcomes in patients with repair failure who
      underwent subsequent partial meniscectomy were poorer than in those with healed
      meniscus repairs. A concern is the 30% overall lack of healing for patients with
      isolated meniscus lesions repaired with the all-inside technique.

PMID- 24114749
TI  - Graft selection in anterior cruciate ligament reconstruction for smoking
      patients.
AB  - BACKGROUND: There has been no previous study regarding graft selection in
      anterior cruciate ligament (ACL) reconstruction for smoking patients. PURPOSE: To
      compare the clinical outcomes of ACL reconstruction between smokers and
      nonsmokers and to find an optimal graft in ACL reconstruction with regard to
      clinical outcomes for smoking patients. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: A total of 487 patients who underwent unilateral ACL
      reconstruction were retrospectively reviewed. Included patients were divided into
      2 groups according to their history of smoking. Group 1 was composed of patients
      who had never smoked (n = 322), and group 2 consisted of patients who had
      reported smoking before ACL reconstruction and during rehabilitation (n = 165).
      Additionally, each group was divided into 4 subgroups according to the selected
      graft type (bone-patellar tendon-bone autograft, hamstring [semitendinosus
      gracilis] tendon autograft, quadriceps tendon-bone autograft, or Achilles tendon
      bone allograft). Patients were assessed for knee instability with the Lachman and
      pivot-shift tests as well as anterior translation measured by the KT-2000
      arthrometer. Functional outcomes were evaluated with the Lysholm knee score,
      International Knee Documentation Committee (IKDC) subjective score, and IKDC
      objective grade. RESULTS: The minimum follow-up period was 24 months. At the
      final follow-up evaluation, there were significant mean between-group differences
      regarding the side-to-side difference in anterior translation (group 1, 2.15 +/-
      1.11 mm; group 2, 2.88 +/- 1.38 mm; P < .001), Lysholm knee score (group 1, 90.25
      +/- 6.18; group 2, 84.79 +/- 6.67; P < .001), IKDC subjective score (group 1,
      89.16 +/- 5.01; group 2, 83.60 +/- 7.48; P < .001), and IKDC objective grade
      (group 1, grade A = 151, B = 130, C = 36, D = 5 patients; group 2, grade A = 48,
      B = 71, C = 37, D = 9 patients; P < .001). With regard to differences in outcomes
      between the selected grafts within each group, the Achilles tendon-bone allograft
      showed the worst outcomes, with statistically significant mean differences for
      smoking patients in the side-to-side difference in anterior translation (3.59 +/-
      1.26 mm), Lysholm knee score (81.05 +/- 2.82), and IKDC subjective score (79.73
      +/- 4.29). CONCLUSION: Unsatisfactory outcomes with regard to stability and
      functional scores were shown in the smoking group compared with the nonsmoking
      group. In smokers, the patients receiving an Achilles tendon-bone allograft had
      poorer outcomes than those with autografts. The bone-patellar tendon-bone
      autograft is recommendable for ACL reconstruction in a smoking patient.

PMID- 24114750
TI  - Arthroscopic repair of large U-shaped rotator cuff tears without margin
      convergence versus repair of crescent- or L-shaped tears.
AB  - BACKGROUND: For large-sized tears of the rotator cuff, data according to the tear
      shape have not yet been reported for repair methodology, configuration, and
      subsequent integrity. HYPOTHESIS: The retear rate after the repair of large
      mobile tears, such as crescent- or L-shaped tears, is believed to be lower
      compared with retear rates after the repair of large U-shaped tears that are
      accompanied by anterior or posterior leaves of the rotator cuff. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: Data were collected and analyzed
      from 95 consecutive patients with a large-sized rotator cuff tear who underwent
      arthroscopic suture-bridge repair. Patients were divided into 2 groups: those
      having crescent- or L-shaped tears (mobile tear group, 53 patients) and those
      having U-shaped tears (U-shaped tear group, 42 patients). The integrity of the
      repaired constructs was determined by ultrasonography at 4.5, 12, and 24 months.
      Moreover, clinical evaluations were performed by using the Constant score, the
      American Shoulder and Elbow Surgeons (ASES) score, and muscle strength at
      intervals of 3, 6, 12, and 24 months postoperatively. RESULTS: On ultrasonography
      at 4.5, 12, and 24 months, a retear was detected in 6, 2, and 1 patients in the
      mobile tear group and in 5, 2, and 1 patients in the U-shaped tear group,
      respectively. Significant differences in retear rates were not detected between
      the groups overall or at each time point. Moreover, clinical scores were similar
      between groups, except for the presence of a temporarily higher Constant score at
      12 months in the mobile tear group. With regard to shoulder strength, between
      group comparisons indicated no statistically significant difference, either in
      abduction or external rotation, except for the presence of temporarily higher
      external rotation strength at 3 months in the mobile tear group. CONCLUSION:
      Arthroscopic repair of large-sized rotator cuff tears yielded substantial
      improvements in shoulder function, regardless of tear retraction, during midterm
      follow-up. Moreover, the findings did not indicate significant differences in
      retear rates between the repair of crescent- or L-shaped tears and that of U
      shaped tears either overall or at a particular time point.

PMID- 24114751
TI  - Clinical results and MRI evolution of a nano-composite multilayered biomaterial
      for osteochondral regeneration at 5 years.
AB  - BACKGROUND: Several cartilage lesions involve the subchondral bone, and there is
      a need for biphasic scaffolds to treat the entire osteochondral unit to reproduce
      the different biological and functional requirements and guide the growth of the
      2 tissues. PURPOSE: To evaluate the results of a cell-free collagen
      hydroxyapatite osteochondral scaffold at midterm, and to use magnetic resonance
      imaging (MRI) analysis to document the imaging evolution of the tissue
      regeneration process through 5 years of follow-up. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Twenty-seven patients (9 women, 18 men; mean age,
      34.9 +/- 10.2 years) treated for knee chondral or osteochondral lesions (size,
      1.5-6 cm(2)) were followed for 2 and 5 years and were clinically evaluated using
      the International Knee Documentation Committee (IKDC) and Tegner scores. An MRI
      evaluation was performed at both follow-ups in 23 lesions, and the magnetic
      resonance observation of cartilage repair tissue (MOCART) score and specific
      subchondral bone parameters (bone regeneration, bone signal quality, osteophytes
      or upcoming bone front, sclerotic areas, and edema) were analyzed. RESULTS: A
      statistically significant improvement in all clinical scores was observed from
      the initial evaluation to the 2- and 5-year follow-ups, and the results were
      stable over time. The mean IKDC subjective score improved from 40.0 +/- 15.0 to
      76.5 +/- 14.5 (2-year follow-up) and 77.1 +/- 18.0 (5-year follow-up) and the
      mean Tegner score from 1.6 +/- 1.1 to 4.0 +/- 1.8 (2-year follow-up) and 4.1 +/-
      1.9 (5-year follow-up). The MRI evaluation showed a significant improvement in
      both the MOCART score and subchondral bone status from 2 to 5 years. At 5 years,
      complete filling of the cartilage was shown in 78.3% of the lesions, complete
      integration of the graft was detected in 69.6% of cases, the repair tissue
      surface was intact in 60.9%, and the structure of the repair tissue was
      homogeneous in 60.9% of the cases. No correlation was found between MRI findings
      and clinical outcome. CONCLUSION: This osteochondral scaffold was used for the
      treatment of chondral and osteochondral knee defects with a single-step
      procedure. The study results highlighted the safety and potential of this
      procedure, which offered a good clinical outcome with stable results at midterm
      follow-up. Although the MRI findings improved over time, some abnormalities
      persisted, but no correlation was found between the imaging and clinical results.

PMID- 24114752
TI  - A biomechanical evaluation of all-inside 2-stitch meniscal repair devices with
      matched inside-out suture repair.
AB  - BACKGROUND: Many all-inside suture-based devices are currently available,
      including the Meniscal Cinch, FasT-Fix, Ultra FasT-Fix, RapidLoc, MaxFire, and
      CrossFix System. These different devices have been compared in various
      configurations, but to our knowledge, the Sequent meniscal repair device, which
      applies running sutures, has not been compared with the Ultra FasT-Fix, nor has
      it been compared with its suture, No. 0 Hi-Fi, using an inside-out repair
      technique. PURPOSE: To assess the quality of the meniscal repair, all new devices
      should be compared with the gold standard: the inside-out repair. To that end,
      this study aims to compare the biomechanical characteristics of running sutures
      delivered by the Sequent meniscal repair device with 2 vertical mattress sutures
      applied using the Ultra FasT-Fix device and with 2 vertical mattress sutures
      using an inside-out repair technique with No. 0 Hi-Fi suture. STUDY DESIGN:
      Controlled laboratory study. METHODS: Paired (medial and lateral), fresh-frozen
      porcine menisci were randomly assigned to 1 of 3 groups: Sequent (n = 17), Ultra
      FasT-Fix (n = 19), and No. 0 Hi-Fi inside-out repair (n = 20). Bucket-handle
      tears were created in all menisci and were subjected to repair according to their
      grouping. Once repaired, the specimens were subjected to cyclic loading (100,
      300, and 500 cycles), followed by loading to failure. RESULTS: The Sequent and
      Ultra FasT-Fix device repairs and the suture repair exhibited low initial
      displacements. The Sequent meniscal repair device demonstrated the lowest
      displacement in response to cyclic loading. No. 0 Hi-Fi suture yielded the
      highest load to failure. CONCLUSION: With the development of the next generation
      of all-inside meniscal repair devices, surgeons may use these findings to select
      the method best suited for their patients. CLINICAL RELEVANCE: The Sequent
      meniscal repair device displays the least amount of displacement during cyclic
      loading but has a similar failure load to other devices.

PMID- 24114753
TI  - Are root avulsions of the lateral meniscus associated with extrusion at the time
      of acute anterior cruciate ligament injury?: a case control study.
AB  - BACKGROUND: Lateral meniscal avulsions left in situ at the time of anterior
      cruciate ligament (ACL) reconstruction do well subjectively. Limited published
      results measure meniscal extrusion of the lateral compartment in this setting.
      PURPOSE: To determine whether an avulsion of the posterior root of the lateral
      meniscus is associated with meniscal extrusion on magnetic resonance imaging
      (MRI). STUDY DESIGN: Cohort study (prevalence); Level of evidence, 2. METHODS: A
      prospective database of surgically treated ACL tears from 2007 to 2012 was
      reviewed. Isolated ACL tears without a concomitant injury were identified along
      with ACL tears in combination with lateral meniscal tears of the posterior root
      (PRLMTs). Thirty-five patients had ACL tears and PRLMTs verified
      arthroscopically, of which 23 patients had preoperative MRI scans available for
      review. From the same database, 25 isolated ACL tears with no meniscal injury
      were randomly chosen for comparison. Plain radiographs were reviewed for
      degenerative joint disease using the Kellgren-Lawrence scale. A board-certified
      radiologist blinded to arthroscopic findings reviewed each MRI scan using
      midcoronal sections to measure extrusion of the lateral meniscus. The average
      extrusion was calculated for each group and compared using a Student t test.
      RESULTS: In the 48 patients reviewed, 1 patient was excluded because of a complex
      lateral meniscal tear that could not be measured on MRI. The remaining 47
      consisted of 22 with root tears and 25 with intact menisci. None of these
      patients were noted to have degenerative joint disease greater than Kellgren
      Lawrence grade 1. All of the patients with PRLMTs were noted to have intact
      meniscofemoral ligaments at the time of arthroscopic surgery. In the patients
      with ACL tears and PRLMTs, the average extrusion was 0.8 mm, and in the ACL tear
      group with an intact meniscus, the average extrusion measured 0.5 mm. No
      significant difference in the amount of extrusion was observed (P = .22).
      CONCLUSION: At the time of acute ACL injuries, PRLMTs do not appear to result in
      meniscal extrusion on MRI.

PMID- 24114754
TI  - Jogging after total hip arthroplasty.
AB  - BACKGROUND: Jogging has been classified as a high-impact sport, and jogging after
      total hip arthroplasty (THA) has not been well documented. PURPOSE: To
      investigate the participation rate for postoperative jogging as well as jogging
      parameters and the influence of jogging on implant stability and bearing wear.
      STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Included in this
      study were 804 hips in 608 patients (85 men, 523 women) who underwent THA between
      2005 and 2011 with follow-up longer than 1 year. The mean patient age was 62
      years (range, 26-98 years), and mean follow-up duration was 4.8 years (range, 2.3
      7.8 years). Hip resurfacing arthroplasty (HRA) was performed in 81 patients and
      conventional THA in 527 patients. During routine postsurgical visits, patients
      were given a questionnaire concerning preoperative and postoperative jogging
      routines. For joggers, frequency, distance, duration, and velocity of jogging
      were recorded. Patients who did not jog postoperatively were asked to provide
      reasons for not jogging. Radiographs concerning implant migration and
      polyethylene wear were evaluated with specialized software, and serum cobalt and
      chromium ion concentrations were investigated for patients with metal-on-metal
      articulation. RESULTS: A total of 33 patients (5.4%) performed jogging
      preoperatively, and 23 patients (3.8%) performed jogging postoperatively. Of the
      23 who jogged postoperatively, conventional THA was performed in 13 patients and
      HRA in 10 patients. Postoperatively, joggers trained a mean of 4 times (range, 1
      7 times) per week, covering a mean distance of 3.6 km (range, 0.5-15 km) in a
      mean time of 29 minutes (range, 5-90 minutes) per session and at a mean speed of
      7.7 km/h (range, 3-18 km/h). No patient complained of pain or showed serum cobalt
      and chromium ion elevation greater than 7 ppb. No hip showed loosening, abnormal
      component migration, or excessive wear at a mean 5-year follow-up. There were 74
      postoperative non-joggers with an interest in jogging. The reasons given for
      avoiding jogging included anxiety (45 patients; 61%); impossible because of
      several reasons, including pain, decreased range of motion, and muscle weakness
      (18 patients; 24%); and lumbar or knee pain (11 patients; 15%). Multivariate
      analysis revealed that male sex and a history of preoperative jogging
      demonstrated significant relationships with postoperative jogging. CONCLUSION: A
      total of 3.8% of THA patients participated in postoperative jogging. Short-term
      postoperative follow-up did not identify any negative influence of jogging on
      implant survival.

PMID- 24114755
TI  - Does a concomitant exposure to lead influence unfavorably the naphthalene
      subchronic toxicity and toxicokinetics?
AB  - Rats were given 20 times during 40 d either naphthalene per gavage or the same
      and lead acetate intraperitoneally in single doses corresponding to 5% of the
      respective 50% lethal doses. The concomitant exposure to lead not only added some
      typical indicators of lead toxicity to the moderate naphthalene intoxication
      picture but also exaggerated some less specific indices for intoxication.
      However, a number of such indices testified to attenuation of naphthalene's
      adverse effects under the impact of lead. Lead also lowered urinary excretion of
      both total and conjugated naphthalene, while the free- to total naphthalene ratio
      in urine sharply increased. These results corroborate implicitly the initial
      hypothesis that lead, being an inhibitor of cytochrome P450, hinders phase I of
      the naphthalene biotransformation and, thus, the formation of derivates which can
      be more toxic but are capable of entering into reactions of conjugation with
      resulting detoxication and elimination of naphthalene from the body.

PMID- 24114757
TI  - Accuracy and validity of sentinel lymph node biopsy for breast cancer using a
      photosensitizer: 8-year follow-up.
AB  - BACKGROUND AND OBJECTIVE: We evaluated an alternative procedure for sentinel
      lymph node biopsy (SLNB) for breast cancer after approval of the study by the
      Ethics Committee of Tokyo Medical University Hospital in 2004. We examined the
      efficacy and safety of SLNB using the photosensitizer talaporfin sodium
      (Laserphyrin(r), Meiji Seika Pharma, Tokoyo, Japan), compared with current
      methods. STUDY DESIGN/PATIENTS AND METHODS: The study included 21 breast cancer
      patients (Japanese women; median age, 54 years; range, 35-75). All patients
      received a breast cancer operation combined with SLNB between June 2004 and May
      2005. Three milliliters of talaporfin solution was locally injected into the
      subareolar region just before the operation. We attempted to identify a sentinel
      lymph node (SLN) that exhibited fluorescence and was consistent with a
      radioisotope (RI) localization technique. Our purpose was to verify the accuracy
      and validity of the talaporfin fluorescence imaging method after 8 years of
      application. RESULTS: There was no consistent correlation between fluorescence
      and pathological SLN metastasis, although all four cases of pathological SLN
      metastasis revealed positive fluorescence. In some cases in which we could not
      identify SLNs by the RI technique, we could identify SLNs using talaporfin. The
      method using talaporfin did not adversely affect the patients after the
      operation, even the chronic renal failure patient. After 8 years, all patients
      are alive, and none had lymph node recurrence. Side effects were not observed.
      CONCLUSION: SLNB using the photosensitizer talaporfin sodium in breast cancer
      patients is considered to be useful as complementary to other current methods. We
      could evaluate the accuracy and validity of this method 8 years after all of the
      procedures were performed. In the future, a large-scale clinical study with
      statistical analyses should be conducted.

PMID- 24114758
TI  - Recent advances in the application of capillary electromigration methods for food
      analysis and Foodomics.
AB  - In this work, the analysis of foods and food components using capillary
      electromigration methods is reviewed. The present work presents and discusses the
      main CE applications performed in Food Science and Technology including the new
      field of Foodomics, reviewing recent results on food quality and safety,
      nutritional value, storage, bioactivity, as well as applications of CE for
      monitoring food interactions and food processing. The CE analysis of a large
      variety of food-related molecules with different chemical properties, including
      amino acids, peptides, proteins, phenolic compounds, carbohydrates, DNA
      fragments, vitamins, toxins, pesticides, additives, and other minor compounds is
      described. The use of microchips, CE-MS, and chiral-CE in food analysis is also
      discussed as well as other current and foreseen trends in this area of research.
      Following the previous review by Castro-Puyana et al. (Electrophoresis, 2012, 33,
      147-167), the current review covers the papers that were published from February
      2011 to February 2013.

PMID- 24114759
TI  - A comparison of reinforcement schedules to increase independent responding in
      individuals with intellectual disabilities.
AB  - We compared the effects of varying reinforcement schedules on independent
      responding with 3 individuals with intellectual disabilities. Independent
      responding was always reinforced, and responding after a vocal response was
      either (a) always reinforced, (b) never reinforced, or (c) reinforced on a fixed
      ratio 3 schedule. Results showed that for 2 of the 3 participants, independent
      responding was higher when responding after the vocal prompt was never
      reinforced. These data suggest that altering the reinforcement schedule to favor
      independent responding may lead to increased independent responding. 

PMID- 24114756
TI  - Using the molecular classification of glioblastoma to inform personalized
      treatment.
AB  - Glioblastoma is the most common and most aggressive diffuse glioma, associated
      with short survival and uniformly fatal outcome, irrespective of treatment. It is
      characterized by morphological, genetic and gene-expression heterogeneity. The
      current standard of treatment is maximal surgical resection, followed by
      radiation, with concurrent and adjuvant chemotherapy. Due to the heterogeneity,
      most tumours develop resistance to treatment and shortly recur. Following
      recurrence, glioblastoma is quickly fatal in the majority of cases. Recent
      genetic molecular advances have contributed to a better understanding of
      glioblastoma pathophysiology and disease stratification. In this paper we review
      basic glioblastoma pathophysiology, with emphasis on clinically relevant genetic
      molecular alterations and potential targets for further drug development.

PMID- 24114760
TI  - Incidence and management of rhinosinusitis after complex orbitofacial
      reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: To examine the sinus-related sequelae of free flap
      reconstruction for complex orbitofacial defects. STUDY DESIGN: Retrospective
      chart review. METHODS: Demographic, clinical, and radiographic data on a series
      of 55 patients who had undergone free tissue transfer for orbitofacial
      reconstruction was retrospectively reviewed. Follow-up of >= 3 months was
      available for 49 patients. Outcome measures studied included clinical or
      radiographic evidence of sinusitis and the need for sinus surgery. RESULTS: The
      most commonly involved sinuses were the ethmoid (n = 40) and maxillary (n = 38)
      sinuses, and the anterolateral thigh was the most common flap used (n = 41).
      Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10
      patients (20%) required sinus surgery at some point during follow-up. Involvement
      of multiple sinuses in the initial orbitofacial surgery was associated with a
      significantly increased need for subsequent sinus surgery (P = 0.009). Adjuvant
      radiotherapy and adjuvant chemoradiotherapy were associated with a significantly
      increased risk for the development of rhinosinusitis (P = 0.045 and 0.016,
      respectively). CONCLUSION: Rhinosinusitis and the need for operative management
      of sinus obstruction are common in patients having undergone complex orbitofacial
      reconstruction. Careful management of the paranasal sinuses is an important
      component of the multidisciplinary treatment of such patients.

PMID- 24114761
TI  - The role of pharmacogenetics in the treatment of chronic hepatitis C infection.
AB  - Hepatitis C virus (HCV) chronically infects 170 million people worldwide. Until
      recently, combination therapy with peginterferon-alpha (pegIFN) and ribavirin
      (RBV) has been the standard of care. However, for many patients, especially those
      infected with the most common HCV genotype 1 (HCV-1), this treatment has resulted
      in unsatisfactory treatment response rates. Many clinical factors, including
      pharmacogenetics, influence the treatment response rate. Genetic variation in the
      interleukin 28B (IL28B) gene is the major determinant of treatment response, a
      finding that has been replicated in multiple independent cohorts. This review
      focuses on the association between pharmacogenetics and conventional pegIFN/RBV
      therapy in patients infected with HCV non-genotype 1; patients reinfected with
      HCV after liver transplantation; and patients coinfected with HCV and human
      immunodeficiency virus. We also review the pharmacogenetic data for boceprevir
      and telaprevir triple therapy in patients with HCV-1 infection, as well as viral
      genomic polymorphisms and genetic variants that may protect against anemia.
      Pharmacogenetic information offers a personalized medicine approach to help
      clinicians and patients make better informed decisions to maximize response and
      minimize toxicity for the treatment of chronic HCV infection. 

PMID- 24114762
TI  - An exploratory analysis of college students' response and reporting behavior
      regarding intimate partner violence victimization and perpetration among their
      friends.
AB  - Over the last several decades, an extensive literature has documented the
      prevalence of dating violence on college campuses. As a result, initiatives to
      promote awareness of dating violence on college campuses have proliferated and
      models of "bystander intervention" have been developed. Bystander intervention
      asserts that by giving all students information concerning the prevalence and
      warning signs of dating violence, these individuals will "say something" when
      they see problem behavior. However, a paucity of empirical research exists
      concerning whether students actually report their observation of dating violence
      among their peers. In the present study, a sample of college freshman (n = 275)
      was surveyed regarding their willingness to report dating violence behaviors
      among their friends. Findings indicate that a slight majority of respondents
      report that they would report dating violence victimization among their friends
      to university officials (54%) and/or law enforcement (56%) while fewer indicated
      they would report perpetration, 38% and 42%, respectively. Importantly,
      respondents overwhelmingly report that they would attempt to intervene in the
      dating violence victimization (87%) and perpetration (84%). Implications of these
      findings for campus safety initiatives and bystander education models are
      discussed. 

PMID- 24114763
TI  - The influence of religiosity on violent behavior of adolescents: a comparison of
      Christian and Muslim religiosity.
AB  - Different criminological theories assume that religiosity protects against
      violent behavior. Up to now, this assumption is tested empirically almost
      exclusively for the Christian religiosity. The study presented here questions
      whether such a relationship between religiosity and violent behavior could be
      found for Muslims, likewise. Using a German-wide representative school survey of
      16,545 male students in the ninth grade, who belong either to a Christian or an
      Islamic denomination, it can be revealed that only for Christians a higher
      religiosity correlates with a lower rate of violent behavior. This influence of
      Christian religiosity can be explained by mainly control theory variables. For
      Muslims, there is no significant correlation between religiosity and violent
      behavior in a bivariate analysis. A multivariate analysis, however, reveals a
      suppression effect: Controlling for alcohol consumption, Muslim religiosity
      increases violent behavior. In addition, high religious Muslims agree more often
      to norms of masculinity and consume more often media violence, which are risk
      factors of violent behavior. Accordingly, it can be concluded that religiosity is
      not a violence-protecting factor in general; instead, a more differentiated view
      for separate religious groups is necessary. 

PMID- 24114764
TI  - Identification of FOXM1-induced epigenetic markers for head and neck squamous
      cell carcinomas.
AB  - BACKGROUND: Epigenetic reprogramming of the methylome has been implicated in all
      stages of cancer evolution. It is now well accepted that cancer cells exploit
      epigenetic reprogramming, a mechanism that regulates stem/progenitor cell renewal
      and differentiation, to promote cancer initiation and progression. The oncogene
      FOXM1 has been implicated in all major forms of human cancer. METHODS: We have
      recently shown that aberrant upregulation of FOXM1 orchestrated a DNA methylation
      signature that mimics the cancer methylome landscape, from which we have
      identified a number of FOXM1-induced epigenetic markers. Differential promoter
      methylation and gene expression in clinical specimens were measured using
      commercially available bisulfite conversion kits and absolute quantitative PCR,
      respectively. RESULTS: Here, we investigated 8 FOXM1-induced differentially
      methylated genes, SPCS1, FLNA, CHPF, GLT8D1, C6orf136, MGAT1, NDUFA10, and
      PAFAH1B3, using human head and neck tissue specimens donated by 2 geographically
      independent patient cohorts from Norway and the United Kingdom. Two genes (GLT8D1
      and C6orf136) were found to be differentially expressed in head and neck squamous
      cell carcinomas (HNSCCs). Using methylation-specific quantitative PCR, we
      confirmed that the promoters of GLT8D1 and C6orf136 were hypo- and
      hypermethylated, respectively, in HNSCC tissues. CONCLUSIONS: Given that
      epigenetic change precedes gene expression, methylation status of candidate genes
      identified from this study may represent a signature of premalignancy, rendering
      them potentially useful predictive biomarkers for precancer screening and/or
      therapeutic targets for cancer prevention.

PMID- 24114766
TI  - Long-term maintenance of HepaRG cells in serum-free conditions and application in
      a repeated dose study.
AB  - Chronic repeated-dose toxicity studies are still carried out on animals and often
      do not correlate with the effects in human beings mainly due to species-specific
      differences in biotransformation. The human hepatoma cell line HepaRG has been
      used for human relevant toxicity assessment. However, HepaRG cells are commonly
      maintained in serum containing medium which limits their use in 'omics'-based
      toxicology. In this study, we compared the maintenance of HepaRG cells in
      standard serum-supplemented and serum-free conditions. Viability and Cytochrome
      P450 (CYP) activity during long-term cultivation were assessed. Liver-specific
      albumin and urea production was measured. The extracellular metabolome (amino
      acids, glucose, lactate and pyruvate) was measured to compare different
      cultivation conditions using metabolic flux analysis. Although metabolic flux
      analysis reveals differences in certain parts of the metabolism, e.g. production
      of urea, the overall metabolism of serum-free and serum-supplemented cultured
      HepaRG cells is similar. We conclude that HepaRG cells can be maintained in
      optimized serum-free conditions for 30 days without viability change and with
      high CYP activity. We also tested the acute (24 h) and long-term repeated-dose (7
      doses, every second day) toxicity of valproic acid. We calculated an EC50 value
      of 1.4 mM after repeated exposure which is close to the cmax value for valproic
      acid. Maintenance of HepaRG cells in serum-free conditions opens up the
      opportunity for the use of these cells in human long-term repeated-dose
      hepatotoxicity studies and for application in systems toxicology.

PMID- 24114765
TI  - Sequence-dependent combination therapy with doxorubicin and a survivin-specific
      small interfering RNA nanodrug demonstrates efficacy in models of adenocarcinoma.
AB  - The clinical management of cancer reflects a balance between treatment efficacy
      and toxicity. While typically, combination therapy improves response rate and
      time to progression compared with sequential monotherapy, it causes increased
      toxicity. Consequently, in cases of advanced cancer, emerging guidelines
      recommend sequential monotherapy, as a means to enhance quality of life. An
      alternative approach that could overcome nonspecific toxicity while retaining
      therapeutic efficacy, involves the combination of chemotherapy with targeted
      therapy. In the current study, we tested the hypothesis that combination therapy
      targeting survivin (BIRC5) and low-dose doxorubicin (Dox) will show enhanced
      therapeutic potential in the treatment of cancer, as compared to monotherapy with
      Dox. We demonstrate in both in vitro and in vivo models of breast cancer that
      combination therapy with a low dose of Dox and an anti-survivin siRNA nanodrug
      (MN-siBIRC5) is superior to mono-therapy with either low- or high-dose Dox alone.
      Importantly, therapeutic efficacy showed prominent sequence dependence. Induction
      of apoptosis was observed only when the cells were treated with Dox followed by
      MN-siBIRC5, whereas the reverse sequence abrogated the benefit of the drug
      combination. In vivo, confirmation of successful sequence dependent combination
      therapy was demonstrated in a murine xenograft model of breast cancer. Finally,
      to determine if the observed effect is not limited to breast cancer, we extended
      our studies to a murine xenograft model of pancreatic adenocarcinoma and found
      similar outcomes as shown for breast cancer. 

PMID- 24114767
TI  - The evaluation of steerable ultrasonic catheters for minimally invasive MRI
      guided cardiac ablation.
AB  - PURPOSE: The purpose of this study was to develop steerable MR-compatible
      ultrasound catheters suitable for minimally invasive MRI-guided cardiac ablation
      therapies. METHODS: MRI-compatible ultrasound steerable catheters were developed
      and tested for their overall tissue heating performance and safety. Ultrasound
      transducers were mounted on a monodirectional deflectable catheter tip that was
      made to be MRI-compatible. Catheter safety was assessed on the potential to form
      hot spots at the distal end of the catheter throughout fast spin echo and
      thermometry scans. Heating experiments were performed on phantoms and ex vivo
      porcine cardiac samples. RESULTS: During catheter safety experiments, a maximum
      temperature increase of 11.35 +/- 0.83 degrees C was evident after a 12-min, 40-s
      fast spin echo scan with a whole body specific absorption rate (SAR) of 1.9 W/kg
      and 1.07 +/- 0.22 degrees C during thermometry scans (flip angle = 90 degrees ;
      scan time = 12 min, 41 s; whole body SAR = 0.34 W/kg). Temperature elevations
      induced by the sonication were shown to be on the order of 38.1 +/- 5.2 degrees C
      for phantom experiments and 49.3 +/- 9.7 degrees C for ex vivo cardiac samples.
      CONCLUSION: Steerable ultrasound catheters have the potential to be safely placed
      in an MR system with little concern of catheter self-heating and driven to heat
      surrounding structures to cause ablations. In addition, these catheters have the
      added benefit of a deflectable tip that allows the treatment of multiple targets
      from within the bore of the MR scanner.

PMID- 24114768
TI  - Impact of frailty and functional status on outcomes in elderly patients with ST
      segment elevation myocardial infarction undergoing primary angioplasty: rationale
      and design of the IFFANIAM study.
AB  - The IFFANIAM study (Impact of frailty and functional status in elderly patients
      with ST segment elevation myocardial infarction undergoing primary angioplasty)
      is an observational multicenter registry to assess the impact of frailty and
      functional status on outcomes of elderly patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing primary angioplasty. STEMI patients age
      75 years or older undergoing primary angioplasty will be extensively studied
      during admission in 4 tertiary care Hospitals in Spain, assessing their baseline
      functional status (Barthel index, Lawton-Brody index), frailty (Fried criteria,
      FRAIL scale [fatigue, resistance, ambulation, illnesses, and loss of weight]),
      comorbidities (Charlson index), nutritional status (Mini Nutritional Assessment
      Short Form), and quality of life (Seattle Angina Questionnaire). Participants
      will be managed according current recommendations. The primary outcome will be
      the description of 1-year mortality, its causes, and associated factors.
      Secondary outcomes will be functional capacity and quality of life. Results will
      help to better understand the impact of frailty and functional ability on
      outcomes in elderly STEMI patients undergoing primary angioplasty, thus
      potentially contributing to improving their clinical management. Higher life
      expectancy has resulted in a large segment of elderly population and an increase
      in myocardial infarction in these patients. This calls attention to healthcare
      systems to focus on promoting methods to improve the clinical management of this
      population. 

PMID- 24114769
TI  - The revolting self: an interpretative phenomenological analysis of the experience
      of self-disgust in females with depressive symptoms.
AB  - OBJECTIVE: Self-focused disgust has been implicated in depression and other
      mental health problems. However, "self-disgust" as a psychological concept has
      never been properly defined and remains particularly enigmatic. A qualitative
      methodology was used to obtain an informed understanding of self-disgust. METHOD:
      Nine female participants with clinically relevant depressive symptoms completed
      semistructured interviews about their understanding and experiences of self
      disgust. These were analyzed using Interpretative Phenomenological Analysis.
      RESULTS: Four superordinate themes emerged: (a) "The subjective experience of
      self-disgust" revealed how self-disgust was perceived as a consuming, visceral
      experience with trait and state components; (b) "Origins of the revolting self"
      covered antecedent factors and the role of others in the genesis of self-disgust;
      (c) "Consequences of self-disgust" included the psychological and behavioral
      results of a disgusting self; and (d) "Associated emotional states" described
      associations between self-disgust and other feeling states. CONCLUSIONS: The
      current findings suggest self-disgust is a consuming negative psychological
      phenomenon, associated with depression, problems with eating, physical
      appearance, interpersonal relationships, and self-persecution. Implications for
      clinical practice and future research on the topic are discussed.

PMID- 24114770
TI  - Vitamin D fortification of eggs for human health.
AB  - BACKGROUND: Vitamin D is an essential component of vertebrate nutrition, and
      epidemiological surveys confirm a chronic vitamin D insufficiency in the human
      population. Eggs are one of the few natural sources rich in vitamin D, containing
      both vitamin D3 (D3) and 25-hydroxyvitamin D3 (25(OH)D3). 25-Hydroxyvitamin D3 is
      especially useful because it provides five times the relative biological activity
      of vitamin D. In order to establish the potential for enrichment of eggs with D3
      and 25(OH)D3, a total of 162 hens were fed three levels of D3 in combination with
      three levels of 25(OH)D3. Egg yolks were analysed for their D3 and 25(OH)D3
      contents, and egg production, egg weights and feed efficiencies were recorded.
      RESULTS: The contents of D3 and 25(OH)D3 in egg yolk increased significantly with
      increasing dietary concentrations. There were no significant differences in egg
      mass, egg weight or feed efficiency. Depending on the dietary concentrations
      used, it was possible to produce eggs with between 100 and 500 IU vitamin D,
      providing scope to meet the recommended daily requirement of vitamin D for
      children or adults. CONCLUSION: The addition of higher levels of D3 and 25(OH)D3
      produced eggs with sufficient vitamin D to meet the recommended daily
      requirements of adults and children without any detrimental effect on production
      parameters.

PMID- 24114771
TI  - SR-A regulates the inflammatory activation of astrocytes.
AB  - Scavenger receptor Class A (SR-A) participates in the regulation of inflammatory
      processes against pathogens and in inflammatory stimulation. We have recently
      demonstrated the presence of SR-A in astrocytes, but its participation in their
      inflammatory response is unknown. Astrocytes regulate neuroinflammation through
      the regulation of microglial cell activation and the production of cytokines,
      neurotrophic factors, and reactive species. Using astrocytes from SR-A(-/-) mice
      in culture, we assessed the participation of SR-A in their inflammatory
      activation, evaluating the activation of IkappaB/NF-kappaB and MAPK signaling
      pathways and the production of nitric oxide (NO) and IL-1beta in response to SR-A
      ligands. In SR-A(-/-) astrocytes, lipopolysaccharide (LPS) induced higher levels
      of NO and reduced levels of IL-1beta compared to SR-A(+/+) cells. In addition, SR
      A(-/-) astrocytes had a reduced basal and LPS-stimulated JNK phosphorylation, and
      a delayed activation on IkappaB/NF-kappaB signaling pathway in response to LPS.
      Moreover, inhibition of the ERK pathway reduced NO production by SR-A(-/-) cells,
      suggesting that this signaling pathway modulated LPS-induced NO production, an
      effect that depended on the presence of SR-A. Our results suggest that SR-A
      participates in the modulation of signaling pathways involved in the production
      of soluble molecules implicated in the neuroinflammatory response. 

PMID- 24114772
TI  - Quantifying and addressing persistent stroke disparities in Hispanics.

PMID- 24114773
TI  - Down syndrome: an electrophysiological and radiological profile.
AB  - OBJECTIVES/HYPOTHESIS: To assess the hearing status of trisomy 21 patients by
      analyzing electrophysiological and radiological findings of any correlation
      between hearing impairment and major or minor inner ear malformations. STUDY
      DESIGN: Prospective radiological and electrophysiological study. METHODS: A group
      of 34 ears of Down syndrome subjects and 20 ears of a volunteer age- and sex
      matched control group of 10 normal subjects were studied electrophysiologically
      by means of otoacoustic emissions and auditory brainstem response. Temporal bone
      computed tomography (CT) scans were carried out in both groups; radiological
      findings were compared. Inner ear structure measurements were applied attempting
      to disclose subtle bony labyrinthine anomalies. The findings from both groups
      were statistically analyzed employing the t test. RESULTS: The rate of
      sensorineural hearing loss (SNHL) in Down syndrome group was 41%. Temporal bone
      CT scans showed no ossicular malformation in all Down syndrome cases. Major inner
      ear abnormalities were disclosed in 5.8%; they corresponded to two cases of
      lateral semicircular canal dysplasia detected on CT images by visual inspection.
      The application of various inner ear structure measurements increased the overall
      detection rate of common inner ear malformations to 47%. A statistically
      significant correlation was found between hearing level and vestibule length (P =
      .009) and internal auditory canal length (P = .028). Vestibular aqueduct width
      was correlated to different otic abnormalities. CONCLUSIONS: SNHL is mainly
      secondary to the underestimated subtle inner ear malformations that are
      adequately demonstrated by adopting standardized inner ear structure measurements
      on petrous bone imaging. Vestibular height and internal auditory canal length
      were correlated to SNHL. LEVEL OF EVIDENCE: 3b.

PMID- 24114774
TI  - Enhanced visibility of colonic neoplasms using formulaic ratio imaging of native
      fluorescence.
AB  - BACKGROUND AND OBJECTIVES: Colonoscopy is the preferred method for colon cancer
      screening, but can miss polyps and flat neoplasms with low color contrast. The
      objective was to develop a new autofluorescence method that improves image
      contrast of colonic neoplasms. STUDY DESIGN/MATERIALS AND METHODS: We selected
      the three strongest native fluorescence signals and developed a novel method
      where fluorescence images are processed in a ratiometric formula to represent the
      likely cellular and structural changes associated with neoplasia. Native
      fluorescence images of fresh surgical specimens of the colon containing normal
      mucosa, polypoid and flat adenomas as well as adenocarcinoma were recorded using
      a prototype multi-spectral imager. Sixteen patients, with a mean age of 62 years
      (range 28-81) undergoing elective resection for colonic neoplasms were enrolled.
      High contrast images were seen with fluorescence from tryptophan (Tryp), flavin
      adenine dinucleotide (FAD) and collagen. RESULTS: When the image intensity of
      Tryp was divided pixel by pixel, by the intensities of FAD and collagen, the
      resulting formulaic ratio (FR) images were of exceptionally high contrast. The FR
      images of adenomas and adenocarcinomas had increased Weber contrast. CONCLUSIONS:
      FR imaging is a novel imaging process that represents the likely metabolic and
      structural changes in colonic neoplasia that produces images with remarkably high
      contrast.

PMID- 24114775
TI  - Endothelin-1 receptor A blocker darusentan decreases hepatic changes and improves
      liver repopulation after cell transplantation in rats.
AB  - Cell transplantation-induced hepatic ischemia and recruitment of vasoconstrictors
      (e.g., endothelin-1; Edn1) leads to clearance of transplanted cells and poses
      problems for liver repopulation. Therefore, we determined whether darusentan
      (DAR), which potently blocks Edn1 receptor type A, could benefit cell
      engraftment. We transplanted primary F344 rat hepatocytes with or without DAR in
      dipeptidyl peptidase IV-deficient rats. Analysis of microcirculatory events
      included hepatic ischemia, endothelial injury, including with gene expression
      arrays, and activations of Kupffer cells (KCs), neutrophils, or hepatic stellate
      cells (HSCs). The retrorsine-partial hepatectomy model was used for liver
      repopulation studies. Whether DAR was directly cytoprotective was examined in
      cultured rat hepatocytes or CFSC-8B rat HSCs. We found that DAR induced hepatic
      sinusoidal vasodilation, caused more transplanted cells to be deposited in liver
      parenchyma, and decreased hepatic ischemia and endothelial injury. This lessened
      perturbations in expression of endothelial biology genes, including regulators of
      vessel tone, inflammation, cell adhesion, or cell damage, versus drug-untreated
      controls. Moreover, in DAR-treated animals, cell transplantation-induced
      activation of KCs, albeit not of neutrophils, decreased, and fewer HSCs expressed
      desmin. In DAR-treated rats, improvements in cell engraftment led to greater
      extent of liver repopulation, compared to drug-untreated controls. In cell
      culture assays, DAR did not stimulate release of cytoprotective factors, such as
      vascular endothelial growth factor, from HSCs. Moreover, DAR did not protect
      hepatocytes from tumor necrosis factor alpha- or oxidative stress-induced
      toxicity. Endothelin receptor A blockade in vitro did not improve engraftment of
      subsequently transplanted hepatocytes. CONCLUSION: Systemic administration of DAR
      decreases hepatic ischemia-related events and thus indirectly improves cell
      engraftment and liver repopulation. This vascular mechanism may permit the
      development of combinatorial drug-based regimens to help optimize cell therapy.

PMID- 24114776
TI  - Catheter ablation of atrial fibrillation in hypertrophic cardiomyopathy: long
      term outcomes and mechanisms of arrhythmia recurrence.
AB  - BACKGROUND: Pulmonary vein (PV) antrum isolation in patients with hypertrophic
      cardiomyopathy and atrial fibrillation (AF) has been reported to have
      satisfactory results at the mid- and short-term follow-up. We determined the
      outcomes at the long-term follow-up of PV antrum isolation in these patients.
      METHODS AND RESULTS: We enrolled 43 patients with hypertrophic cardiomyopathy and
      AF (28% paroxysmal AF). PV antrum isolation (paroxysmal AF) and posterior wall
      isolation with complex fractionated atrial electrogram ablation (persistent and
      longstanding persistent AF) were the end points at the time of the index
      procedure and for repeat procedures during the first year of follow-up. In case
      of recurrent arrhythmia >1 year, high-dose isoproterenol challenge was used to
      disclose non-PV trigger sites. During the first year, the success rate reached
      91% (mean of 1.6 procedures). After a median follow-up of 42 months (range, 38-48
      months), 49% of the patients remained free from AF/atrial tachycardia. All
      patients underwent an additional procedure. PV antrum and posterior wall remained
      isolated in 82% of the cases, and extra-PV triggers were documented in all
      patients and targeted for ablation. After a median follow-up of 15 months (range,
      8-19 months) subsequent to the last procedure, 94% of the patients remained free
      from AF/atrial tachycardia off antiarrhythmic drugs. CONCLUSIONS: PV isolation in
      patients with hypertrophic cardiomyopathy is feasible and safe, although is not
      effective in preventing late (>=1 year) AF recurrences in ~50% of patients. Non
      PV triggers seem to be responsible of late recurrences, which supports the
      appropriateness of a more extensive ablation beyond PV isolation to improve the
      long-term arrhythmia-free survival.

PMID- 24114777
TI  - Novel electromyographic monitoring technique for prevention of right phrenic
      nerve palsy during cryoballoon ablation.
AB  - BACKGROUND: Right phrenic nerve palsy (PNP) is the most frequent complication of
      cryoballoon ablation. Diaphragmatic electromyography can predict PNP with a
      comfortable safety margin. Our goal was to evaluate the feasibility, efficacy,
      and safety of electromyography-guided PN monitoring using a novel hepatic vein
      approach for prevention of PNP. METHODS AND RESULTS: This study includes 57
      patients (47 males) indicated for cryoballoon ablation for treatment of atrial
      fibrillation. During right superior pulmonary vein ablation, the PN was paced at
      60 beats per minute and diaphragmatic compound motor action potential (CMAP)
      amplitude was recorded via a quadripolar catheter positioned in a
      subdiaphragmatic hepatic vein. If a 30% drop in CMAP amplitude was observed,
      ablation was discontinued with forced deflation. Reliable recording of CMAP
      before ablation was feasible in 50 of 57 patients (88%). In 7 patients (12%),
      stable PN pacing could not be achieved. In 44 of 50 patients, CMAP amplitude
      remained constant during cryoapplication. The mean value of CMAP amplitude was
      639.7+/-240.5 uV; mean variation was 13+/-4.3%. In 6 of 50 patients (12%)
      including 5 treated with a 23-mm cryoballoon and 1 with a 28-mm cryoballoon, the
      30% reduction cutoff was reached and cryoablation was discontinued. Recovery of
      CMAP amplitude after discontinuing cryoablation took <60 seconds in all cases. No
      PNP or complication related to PN monitoring occurred. CONCLUSIONS: Recording of
      diaphragmatic CMAP using a catheter positioned in a subdiaphragmatic hepatic vein
      seems feasible during cryoballoon ablation. Electromyography-guided PN monitoring
      seems safe and potentially helpful for prevention of PNP.

PMID- 24114778
TI  - Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: a
      review.
AB  - The study reviews the current state of knowledge regarding the biotransformation
      of fluorotelomer-based compounds, with a focus on compounds that ultimately
      degrade to form perfluoroalkyl carboxylates (PFCAs). Most metabolism studies have
      been performed with either microbial systems or rats and mice, and comparatively
      few studies have used fish models. Furthermore, biotransformation studies thus
      far have predominately used the 8:2 fluorotelomer alcohol (FTOH) as the
      substrate. However, there have been an increasing number of studies investigating
      6:2 FTOH biotransformation as a result of industry's transition to shorter-chain
      fluorotelomer chemistry. Studies with the 8:2 FTOH metabolism universally show
      the formation of perfluorooctanoate (PFOA) and, to a smaller fraction,
      perfluorononanoate (PFNA) and lower-chain-length PFCAs. In general, the overall
      yield of PFOA is low, presumably because of the multiple branches in the
      biotransformation pathways, including conjugation reactions in animal systems.
      There have been a few studies of non-FTOH biotransformation, which include
      polyfluoroalkyl phosphates (PAPs), 8:2 fluorotelomer acrylate (8:2 FTAC), and
      fluorotelomer carboxylates (FTCAs, FTUCAs). The PAPs compounds and 8:2 FTAC were
      shown to be direct precursors to FTOHs and thus follow similar degradation
      pathways.

PMID- 24114779
TI  - Very fast electrophoretic determination of creatinine and uric acid in human
      urine using a combination of two capillaries with different internal diameters.
AB  - A capillary system formed by combining 25 and 100 MUm id capillaries was used in
      the short-end injection mode to determine creatinine and uric acid in human
      urine. The separation was performed at an electric field intensity of 2.3 kV/cm.
      Creatinine was determined in a BGE with a composition of 20 mM citric acid/NaOH
      (pH 3.0), and uric acid was determined in 20 mM MES/NaOH (pH 6.0). Under these
      conditions, migration times of 12.2 s for creatinine and 8.6 s for uric acid were
      achieved. The LOD value is 2.4 mg/L for creatinine and 0.9 mg/L for uric acid;
      the RSD for the migration time varies in the range 0.7-1.1% (intra day) to 1.0
      7.5% (inter day); RSDs for the peak areas equalled 3.4-4.0% (intra day) and 4.3
      4.7% (inter day). The determined creatinine values in seven urine samples vary in
      the range 221-1394 mg/L for creatinine and 87-615 mg/L for uric acid. t-Test did
      not reveal any statistically significant difference between the developed CE
      methodologies and reference methods - Jaffe reaction for creatinine and enzymatic
      uricase test for uric acid.

PMID- 24114781
TI  - 2000 years of parallel societies in Stone Age Central Europe.
AB  - Debate on the ancestry of Europeans centers on the interplay between Mesolithic
      foragers and Neolithic farmers. Foragers are generally believed to have
      disappeared shortly after the arrival of agriculture. To investigate the relation
      between foragers and farmers, we examined Mesolithic and Neolithic samples from
      the Blatterhohle site. Mesolithic mitochondrial DNA sequences were typical of
      European foragers, whereas the Neolithic sample included additional lineages that
      are associated with early farmers. However, isotope analyses separate the
      Neolithic sample into two groups: one with an agriculturalist diet and one with a
      forager and freshwater fish diet, the latter carrying mitochondrial DNA sequences
      typical of Mesolithic hunter-gatherers. This indicates that the descendants of
      Mesolithic people maintained a foraging lifestyle in Central Europe for more than
      2000 years after the arrival of farming societies. 

PMID- 24114782
TI  - Abrupt shifts in Horn of Africa hydroclimate since the Last Glacial Maximum.
AB  - The timing and abruptness of the initiation and termination of the Early Holocene
      African Humid Period are subjects of ongoing debate, with direct consequences for
      our understanding of abrupt climate change, paleoenvironments, and early human
      cultural development. Here, we provide proxy evidence from the Horn of Africa
      region that documents abrupt transitions into and out of the African Humid Period
      in northeast Africa. Similar and generally synchronous abrupt transitions at
      other East African sites suggest that rapid shifts in hydroclimate are a
      regionally coherent feature. Our analysis suggests that the termination of the
      African Humid Period in the Horn of Africa occurred within centuries,
      underscoring the nonlinearity of the region's hydroclimate. 

PMID- 24114780
TI  - Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T
      cells.
AB  - Immunotherapies that augment antitumor T cells have had recent success for
      treating patients with cancer. Here we examined whether tumor-specific CD4(+) T
      cells enhance CD8(+) T-cell adoptive immunotherapy in a lymphopenic environment.
      Our model employed physiological doses of tyrosinase-related protein 1-specific
      CD4(+) transgenic T cells-CD4(+) T cells and pmel-CD8(+) T cells that when
      transferred individually were subtherapeutic; however, when transferred together
      provided significant (p <= 0.001) therapeutic efficacy. Therapeutic efficacy
      correlated with increased numbers of effector and memory CD8(+) T cells with
      tumor-specific cytokine expression. When combined with CD4(+) T cells, transfer
      of total (naive and effector) or effector CD8(+) T cells were highly effective,
      suggesting CD4(+) T cells can help mediate therapeutic effects by maintaining
      function of activated CD8(+) T cells. In addition, CD4(+) T cells had a
      pronounced effect in the early posttransfer period, as their elimination within
      the first 3 days significantly (p < 0.001) reduced therapeutic efficacy. The
      CD8(+) T cells recovered from mice treated with both CD8(+) and CD4(+) T cells
      had decreased expression of PD-1 and PD-1-blockade enhanced the therapeutic
      efficacy of pmel-CD8 alone, suggesting that CD4(+) T cells help reduce CD8(+) T
      cell exhaustion. These data support combining immunotherapies that elicit both
      tumor-specific CD4(+) and CD8(+) T cells for treatment of patients with cancer. 

PMID- 24114783
TI  - Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron
      peroxidase.
AB  - The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1-phosphonate (S
      HPP) to the antibiotic fosfomycin [(1R,2S)-epoxypropylphosphonate] in an unusual
      1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been
      classified as an oxidase, with proposed mechanisms differing primarily in the
      identity of the O2-derived iron complex that abstracts hydrogen (H*) from C1 of S
      HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate
      is actually H2O2 and that HppE therefore almost certainly uses an iron(IV)-oxo
      complex as the H* abstractor. Reaction with H2O2 is accelerated by bound
      substrate and produces fosfomycin catalytically with a stoichiometry of unity.
      The ability of catalase to suppress the HppE activity previously attributed to
      its direct utilization of O2 implies that reduction of O2 and utilization of the
      resultant H2O2 were actually operant. 

PMID- 24114784
TI  - The Hippo signaling pathway interactome.
AB  - The Hippo pathway controls metazoan organ growth by regulating cell proliferation
      and apoptosis. Many components have been identified, but our knowledge of the
      composition and structure of this pathway is still incomplete. Using existing
      pathway components as baits, we generated by mass spectrometry a high-confidence
      Drosophila Hippo protein-protein interaction network (Hippo-PPIN) consisting of
      153 proteins and 204 interactions. Depletion of 67% of the proteins by RNA
      interference regulated the transcriptional coactivator Yorkie (Yki) either
      positively or negatively. We selected for further characterization a new member
      of the alpha-arrestin family, Leash, and show that it promotes degradation of Yki
      through the lysosomal pathway. Given the importance of the Hippo pathway in tumor
      development, the Hippo-PPIN will contribute to our understanding of this network
      in both normal growth and cancer. 

PMID- 24114785
TI  - Strong premelting effect in the elastic properties of hcp-Fe under inner-core
      conditions.
AB  - The observed shear-wave velocity VS in Earth's core is much lower than expected
      from mineralogical models derived from both calculations and experiments. A
      number of explanations have been proposed, but none sufficiently explain the
      seismological observations. Using ab initio molecular dynamics simulations, we
      obtained the elastic properties of hexagonal close-packed iron (hcp-Fe) at 360
      gigapascals up to its melting temperature Tm. We found that Fe shows a strong
      nonlinear shear weakening just before melting (when T/Tm > 0.96), with a
      corresponding reduction in VS. Because temperatures range from T/Tm = 1 at the
      inner-outer core boundary to T/Tm ~ 0.99 at the center, this strong nonlinear
      effect on VS should occur in the inner core, providing a compelling explanation
      for the low VS observed. 

PMID- 24114786
TI  - Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune
      complex.
AB  - Flagellin perception in Arabidopsis is through recognition of its highly
      conserved N-terminal epitope (flg22) by flagellin-sensitive 2 (FLS2). Flg22
      binding induces FLS2 heteromerization with BRASSINOSTEROID INSENSITIVE 1
      associated kinase 1 (BAK1) and their reciprocal activation followed by plant
      immunity. Here, we report the crystal structure of FLS2 and BAK1 ectodomains
      complexed with flg22 at 3.06 angstroms. A conserved and a nonconserved site from
      the inner surface of the FLS2 solenoid recognize the C- and N-terminal segment of
      flg22, respectively, without oligomerization or conformational changes in the
      FLS2 ectodomain. Besides directly interacting with FLS2, BAK1 acts as a co
      receptor by recognizing the C terminus of the FLS2-bound flg22. Our data reveal
      the molecular mechanisms underlying FLS2-BAK1 complex recognition of flg22 and
      provide insight into the immune receptor complex activation. 

PMID- 24114787
TI  - Improvement in survival of patients with oral cavity squamous cell carcinoma: An
      international collaborative study.
AB  - BACKGROUND: An association between the survival of patients with oral cavity
      squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not
      been established. METHODS: This was a retrospective, longitudinal, international,
      population-based study of 2738 patients who underwent resection of OCSCC during 2
      different decades. Characteristics of patients from 7 international cancer
      centers who received treatment between 1990 and 2000 (group A; n = 735) were
      compared with patients who received treatment between 2001 and 2011 (group B; n =
      2003). RESULTS: Patients in group B had more advanced tumors and tended to
      develop distant metastases more frequently than patients in group A (P = .005).
      More group B patients underwent selective neck dissection and received adjuvant
      radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5
      year overall survival, from 59% for group A to 70% for group B (P < .001). There
      was also a significant improvement in disease-specific survival associated with
      operations performed before and after 2000 (from 69% to 81%, respectively; P <
      .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage
      disease were independent predictors of a better outcome in multivariate analysis.
      The decade of treatment was an independent prognostic factor for cancer-specific
      mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). CONCLUSIONS:
      The survival rate of patients with OCSCC improved significantly during the past 2
      decades despite older age, more advanced disease stage, and a higher rate of
      distant metastases. The current results suggest that the prognosis for patients
      with OCSCC has improved over time, presumably because of advances in imaging and
      therapy.

PMID- 24114788
TI  - Caregiver- and staff-conducted functional analysis outcomes: a summary of 52
      cases.
AB  - In the present study, caregivers were trained as therapists to conduct functional
      analyses (FAs) after staff-conducted FAs were inconclusive with 52 participants.
      Caregiver-conducted FAs identified at least 1 function for problem behavior when
      staff-conducted FAs were undifferentiated. When results of the staff-conducted
      FAs were questionable, subsequent caregiver-conducted FAs resulted in an exact
      match with staff-conducted FA in about 68% of cases but identified new functions
      in about 30% of cases. Function-based treatments based on caregiver-conducted FAs
      were effective in reducing problem behavior by an average of 96% relative to
      baseline. Results suggest that when staff-conducted FA outcomes yield
      inconclusive findings, using caregivers to conduct FAs is likely to produce
      differentiated results and ultimately result in the development of effective
      treatments. 

PMID- 24114790
TI  - Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR
      TKIs and mTOR inhibitor.
AB  - Angiogenesis and immunosuppression work hand-in-hand in the renal cell carcinoma
      (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune
      response in RCC, which involves T cells, natural killer cells, dendritic cells
      (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such
      as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of
      rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both
      antiangiogenic and immunomodulatory functions. Indeed, these agents affect
      neutrophil migration, as well as T lymphocyte-DC cross-talk, DC maturation and
      immune cell metabolism and reactivity. In this review, we overview the essential
      role of innate and adaptive immune response in RCC proliferation, invasion and
      metastasis and the relationship between tumor-associated immune cells and the
      response to targeted agents approved for the treatment of metastatic RCC. 

PMID- 24114789
TI  - High-throughput biophysical analysis and data visualization of conformational
      stability of an IgG1 monoclonal antibody after deglycosylation.
AB  - The structural integrity and conformational stability of an IgG1 monoclonal
      antibody (mAb), after partial or complete enzymatic removal of the N-linked Fc
      glycan, were compared with the untreated mAb over a wide range of temperature (10
      degrees C-90 degrees C) and solution pH (3-8) using circular dichroism,
      fluorescence spectroscopy, and static light scattering combined with data
      visualization employing empirical phase diagrams. Subtle-to-larger stability
      differences between the different glycoforms were observed. Improved detection of
      physical stability differences was then demonstrated over narrower pH range (4.0
      6.0) using smaller temperature increments, especially when combined with an
      alternative data visualization method (radar plots). Differential scanning
      calorimetry and differential scanning fluorimetry were then utilized and also
      showed an improved ability to detect differences in the physical stability of a
      mAb glycoform. On the basis of these results, a two-step methodology was used in
      which conformational stability of a mAb glycoform is first screened with a wide
      variety of instruments and environmental stresses, followed by a second
      evaluation with optimally sensitive experimental conditions, analytical
      techniques, and data visualization methods. With this approach, a high-throughput
      biophysical analysis to assess relatively subtle conformational stability
      differences in protein glycoforms is demonstrated.

PMID- 24114791
TI  - Correlation between bacterial biofilms and osteitis in patients with chronic
      rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Bacterial biofilms (BBF) and osteitis are potential
      contributors to the local inflammatory load in chronic rhinosinusitis (CRS). This
      study investigated the relationship between BBF and osteitis status in CRS
      patients. STUDY DESIGN: Prospective cohort study. METHODS: Eighty-four CRS
      patients undergoing endoscopic sinus surgery and 22 control patients were
      enrolled in this study. Mucosal and bony samples from ethmoid sinus were obtained
      for confocal scanning laser microscopy and microscopic examination. Biofilm
      volume (BV), biofilm score (BS), histopathologic bony grade, Global Osteitis
      Scoring Scale (GOSS) score, and Hounsfield unit (HU) value on computed tomography
      were recorded. Associations between these parameters describing BBF and osteitis
      were assessed. RESULTS: The histopathologic bony grade 2 (0-3) versus 0 (0-3) (P
      < 0.001), GOSS score 4.5 (0-31) versus 0 (0-26) (P = 0.014) and HU value 431.5
      (310-509) versus 354 (288-499) (P < 0.001) in patients with BBF were greater than
      those without BBF. The bony grade (r = 0.683, P < 0.001 and r = 0.664, P <
      0.001), GOSS score (r = 0.314, P = 0.004 and r = 0.312, P = 0.004), and HU value
      (r = 0.539, P < 0.001 and r = 0.520, P < 0.001) were significantly increased with
      higher BV and BS. CONCLUSION: A total of 84.8% of the bone underlying mucosa with
      BBF had some form of osteitis in ethmoid sinus, and approximately 46.4% of CRS
      patients were from a subgroup with both BBF and osteitis. The volume of BBF
      correlated well with severity of osteitis in CRS patients.

PMID- 24114792
TI  - Mobuck virus genome sequence and phylogenetic analysis: identification of a novel
      Orbivirus isolated from a white-tailed deer in Missouri, USA.
AB  - The genus Orbivirus includes a diverse group of segmented dsRNA viruses that are
      transmitted via arthropods, have a global distribution and affect a wide range of
      hosts. A novel orbivirus was co-isolated with epizootic haemorrhagic disease
      virus (EHDV) from a white-tailed deer (Odocoileus virginianus) exhibiting
      clinical signs characteristic of EHDV. Using antiserum generated against EHDV, a
      pure isolate of the novel non-cytopathic orbivirus was obtained in Aedes
      albopictus cell culture. Genomic sequencing and phylogenetic analysis of
      predicted ORFs showed that eight of the ten ORFs were most homologous to Peruvian
      horse sickness virus (PHSV), with amino acid identities of 44.3-73.7 %. The
      remaining two ORFs, VP3 and VP5, were most similar to Middle Point orbivirus
      (35.9 %) and Yunnan orbivirus (59.8 %), respectively. Taxonomic classification of
      orbiviruses is largely based on homology of the major subcore structural protein
      VP2(T2), encoded by segment 2 for mobuck virus. With only 69.1 % amino acid
      identity to PHSV, we propose mobuck virus as the prototype of a new species of
      Orbivirus. 

PMID- 24114794
TI  - Poly-proline motif in HIV-2 Vpx is critical for its efficient translation.
AB  - Human immunodeficiency virus type 2 (HIV-2) carries an accessory protein Vpx that
      is important for viral replication in natural target cells. In its C-terminal
      region, there is a highly conserved poly-proline motif (PPM) consisting of seven
      consecutive prolines, encoded in a poly-pyrimidine tract. We have previously
      shown that PPM is critical for Vpx expression and viral infectivity. To elucidate
      the molecular basis underlying this observation, we analysed the expression of
      Vpx proteins with various PPM mutations by in vivo and in vitro systems. We found
      that the number and position of consecutive prolines in PPM are important for Vpx
      expression, and demonstrated that PPM is essential for efficient Vpx translation.
      Furthermore, mutational analysis to synonymously disrupt the poly-pyrimidine
      tract suggested that the context of PPM amino acid sequences is required for
      efficient translation of Vpx. We similarly analysed HIV-1 and HIV-2 Vpr proteins
      structurally related to HIV-2 Vpx. Expression level of the two Vpr proteins
      lacking PPM was shown to be much lower relative to that of Vpx, and not
      meaningfully enhanced by introduction of PPM at the C terminus. Finally, we
      examined the Vpx of simian immunodeficiency virus from rhesus monkeys (SIVmac),
      which also has seven consecutive prolines, for PPM-dependent expression. A multi
      substitution mutation in the PPM markedly reduced the expression level of SIVmac
      Vpx. Taken together, it can be concluded that the notable PPM sequence enhances
      the expression of Vpx proteins from viruses of the HIV-2/SIVmac group at the
      translational level. 

PMID- 24114793
TI  - Human metapneumovirus inhibits the IL-6-induced JAK/STAT3 signalling cascade in
      airway epithelium.
AB  - The host cytokine IL-6 plays an important role in host defence and prevention of
      lung injury from various pathogens, making IL-6 an important mediator in the
      host's susceptibility to respiratory infections. The cellular response to IL-6 is
      mediated through a Janus kinase/signal transducer and activator of transcription
      3 (JAK/STAT3) signal transduction pathway. Human metapneumovirus (hMPV) is an
      important causative agent of viral respiratory infections known to inhibit the
      IFN-mediated activation of STAT1. However, little is known about the interactions
      between this virus and other STAT signalling cascades. Herein, we showed that
      hMPV can attenuate the IL-6-mediated JAK/STAT3 signalling cascade in lung
      epithelial cells. HMPV inhibited a key event in this pathway by impeding the
      phosphorylation and nuclear translocation of STAT3 in A549 cells and in primary
      normal human bronchial epithelial cells. Further studies established that hMPV
      interrupted the IL-6-induced JAK/STAT pathway early in the signal transduction
      pathway by blocking the phosphorylation of JAK2. By antagonizing the IL-6
      mediated JAK/STAT3 pathway, hMPV perturbed the expression of IL-6-inducible genes
      important for apoptosis, cell differentiation and growth. Infection with hMPV
      also differentially regulated the effects of IL-6 on apoptosis. Thus, hMPV
      regulation of these genes could usurp the protective roles of IL-6, and these
      data provide insight into an important element of viral pathogenesis. 

PMID- 24114795
TI  - Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis
      virus-induced unfolded protein response and benefits viral replication.
AB  - Japanese encephalitis virus (JEV) infection-induced encephalitis causes extensive
      death or long-term neurological damage, especially among children, in south and
      south-east Asia. Infection of mammalian cells has shown induction of an unfolded
      protein response (UPR), presumably leading to programmed cell death or apoptosis
      of the host cells. UPR, a cellular response to accumulation of unfolded or
      misfolded proteins in the endoplasmic reticulum (ER) lumen, is initiated by three
      ER-lumen-resident sensors (PERK, IRE1 and ATF6), and involves transcriptional and
      translational regulation of the expression of several genes. The sensor IRE1
      possesses an intrinsic RNase activity, activated through homo-dimerization and
      autophosphorylation during UPR. Activated IRE1 performs cytoplasmic cleavage of
      Xbp1u transcripts, thus facilitating synthesis of XBP1S transcription factor, in
      addition to cleavage of a cohort of cellular transcripts, the later initiating
      the regulated IRE1-dependent decay (RIDD) pathway. In this study, we report the
      initiation of the RIDD pathway in JEV-infected mouse neuroblastoma cells
      (Neuro2a) and its effect on viral infection. Activation of the RIDD pathway led
      to degradation of known mouse cell target transcripts without showing any effect
      on JEV RNA despite the fact that both when biochemically purified showed
      significant enrichment in ER membrane-enriched fractions. Additionally,
      inhibition of the IRE1 RNase activity by STF083010, a specific drug, diminished
      viral protein levels and reduced the titre of the virus produced from infected
      Neuro2a cells. The results present evidence for the first report of a beneficial
      effect of RIDD activation on the viral life cycle. 

PMID- 24114796
TI  - Predicting the sensitivity of populations from individual exposure to chemicals:
      the role of ecological interactions.
AB  - Population responses to chemical stress exposure are influenced by nonchemical,
      environmental processes such as species interactions. A realistic quantification
      of chemical toxicity to populations calls for the use of methodologies that
      integrate these multiple stress effects. The authors used an individual-based
      model for Daphnia magna as a virtual laboratory to determine the influence of
      ecological interactions on population sensitivity to chemicals with different
      modes of action on individuals. In the model, hypothetical chemical toxicity
      targeted different vital individual-level processes: reproduction, survival,
      feeding rate, or somatic growth rate. As for species interactions, predatory and
      competition effects on daphnid populations were implemented following a worst
      case approach. The population abundance was simulated at different food levels
      and exposure scenarios, assuming exposure to chemical stress solely or in
      combination with either competition or predation. The chemical always targeted
      one vital endpoint. Equal toxicity-inhibition levels differently affected the
      population abundance with and without species interactions. In addition,
      population responses to chemicals were highly sensitive to the environmental
      stressor (predator or competitor) and to the food level. Results show that
      population resilience cannot be attributed to chemical stress only. Accounting
      for the relevant ecological interactions would reduce uncertainties when
      extrapolating effects of chemicals from individuals to the population level.
      Validated population models should be used for a more realistic risk assessment
      of chemicals.

PMID- 24114797
TI  - Narrative enhancement and cognitive therapy (NECT) effectiveness: a quasi
      experimental study.
AB  - OBJECTIVE: Accumulated evidence suggests that approximately one third of people
      with a serious mental illness (SMI) experience elevated self-stigma. Narrative
      enhancement and cognitive therapy (NECT) is a structured group-based intervention
      aimed to reduce self-stigma. The current study aims to examine the effectiveness
      of NECT. A quasi-experimental design. DESIGN: Baseline and follow-up data were
      collected and outcomes were compared between 63 persons with SMI who participated
      in NECT and 56 persons who received treatment as usual. RESULTS: The NECT
      treatment group showed significant (p < .05) reductions in self-stigma and
      increases in self-esteem, quality of life, and Hope-Agency scores between pre-
      and posttreatment assessments, compared with the control group. CONCLUSIONS: The
      current results provide preliminary support for the use of NECT as an effective
      treatment to reduce self-stigma and its implications for treatment and practice
      are discussed.

PMID- 24114798
TI  - Droplet Array Platform for High-Resolution Melt Analysis of DNA Methylation
      Density.
AB  - High-resolution melting (HRM) has garnered significant interest as an analytical
      technique for a number of applications, including DNA methylation detection, due
      to its inherent sensitivity and robustness. In this study, we describe a
      miniaturized assay platform for quantitative methylation density analysis using a
      microfluidic droplet array cartridge. We demonstrate that the DNA methylation
      level of the RASSF1A promoter can be directly analyzed using HRM. PCR products
      were generated by amplifying bisulfite-treated DNA with varying CpG densities
      using CpG island-flanking primer sets. Subsequent HRM analysis on the
      miniaturized droplet platform shows distinct melting curve profiles associated
      with methylation levels, which was verified using a conventional benchtop PCR-HRM
      system. The characteristic melting temperature (Tm) of the PCR products was used
      to directly quantify the respective levels of DNA methylation density. Our
      approach provides a key advantage over current gold standard methods such as
      methylation-specific PCR (MSP), which are incapable of providing specific
      information regarding the overall methylation density of the target genes. The
      miniaturized platform establishes a practical approach to methylation density
      profiling from multiple DNA samples with a potential application in point-of-care
      diagnostics. 

PMID- 24114799
TI  - Circulating microRNAs as biomarkers of retinal toxicity.
AB  - Despite of the attrition due to retinal toxicity during drug development there
      are no early reliable predictive biomarkers of retinal toxicity and this is
      increasingly becoming a concern. Thus far, in pharmacology and toxicology the
      technologies for assessing retinal side effects are limited to inconvenient
      visual behavioral tests, invasive electroretinograms or terminal histopathology.
      To address the lack of convenient early predictive retinal toxicity biomarkers,
      we explored a set of potential novel retinal enriched miRNAs in rats ex vivo and
      in vivo with known retinal toxicant pan-CDK inhibitors to assess circulating
      plasma miRNAs in rats and non-retinal toxicants as controls. Rats were
      administered a single intravitreal (IVT) injection and blood samples were
      collected pre-dose, various time points post-dose and then analyzed for five
      retinal enriched miRNAs (miR-96, miR-124a, miR181a, miR-182 and miR-183) by qRT
      PCR. Ophthalmic exam, electroretinogram and histopathology were performed as
      confirmatory tests. All five miRNAs tested in retinal explants culture were
      highly expressed after pan-CDK inhibitor treatment. In vivo the pan-CDK
      inhibitors caused elevations of miR-96, miR-124a and miR-183 in blood. These
      results highly correlated with ocular exam, electroretinograms and microscopic
      findings. Comparatively, there were no changes in miRNA levels,
      electroretinograms, or histopathology in the negative control treatment groups.
      Although these miRNAs need additional confirmatory evaluation whether they truly
      predict retinal toxicity prior to clinical observations and histopathology, these
      results provide promise for further testing using additional retinal toxicants.

PMID- 24114800
TI  - Characterization of pandemic influenza A (H1N1) virus hemagglutinin specific
      polyclonal antibodies for biosensor applications.
AB  - In this study, recombinant hemagglutinin protein (rH1N1HA) of Pandemic influenza
      virus and polyclonal antibodies against it for biosensor applications have been
      characterized. For rapid and high sensitive detection of H1N1 virus or its
      antibodies, PCR-free and label free detection method based on a surface plasmon
      resonance technique has been proposed. The glycosylated H1N1HA protein was
      expressed in yeast and the authenticity of the expressed protein was confirmed by
      Western blotting. Rabbit polyclonal antibodies developed against rH1N1HA protein
      were evaluated for their ability to neutralize H1N1 virus through plaque
      reduction neutralization test and indirect ELISA. Affinity purified anti-H1N1HA
      IgG were characterized further for their specificity, affinity of interaction,
      the association and dissociation rates at which they interact through surface
      plasmon resonance technique. The equilibrium constant and maximum binding
      capacity of analyte was found to be 49.7 nM and 47.28m degrees , respectively.
      The assay could detect a lowest IgG of 0.5 ng on a rH1N1HA coated chip. Combined
      with the high sensitivity of surface plasmon resonance technique and specificity
      of the reagents, it is possible to develop a rapid detection assay for monitoring
      influenza infections.

PMID- 24114801
TI  - Stable isotope-labelled feed nutrients to assess nutrient-specific feed passage
      kinetics in ruminants.
AB  - Knowledge of digesta passage kinetics in ruminants is essential to predict
      nutrient supply to the animal in relation to optimal animal performance,
      environmental pollution and animal health. Fractional passage rates (FPR) of feed
      are widely used in modern feed evaluation systems and mechanistic rumen models,
      but data on nutrient-specific FPR are scarce. Such models generally rely on
      conventional external marker techniques, which do not always describe digesta
      passage kinetics in a satisfactory manner. Here the use of stable isotope
      labelled dietary nutrients as a promising novel tool to assess nutrient-specific
      passage kinetics is discussed. Some major limitations of this technique include a
      potential marker migration, a poor isotope distribution in the labelled feed and
      a differential disappearance rate of isotopes upon microbial fermentation in non
      steady state conditions. Such limitations can often be circumvented by using
      intrinsically stable isotope-labelled plant material. Data are limited but
      indicate that external particulate markers overestimate rumen FPR of plant fibre
      compared with the internal stable isotope markers. Stable isotopes undergo the
      same digestive mechanism as the labelled feed components and are thus of
      particular interest to specifically measure passage kinetics of digestible
      dietary nutrients.

PMID- 24114802
TI  - Mendelian randomization analysis with multiple genetic variants using summarized
      data.
AB  - Genome-wide association studies, which typically report regression coefficients
      summarizing the associations of many genetic variants with various traits, are
      potentially a powerful source of data for Mendelian randomization investigations.
      We demonstrate how such coefficients from multiple variants can be combined in a
      Mendelian randomization analysis to estimate the causal effect of a risk factor
      on an outcome. The bias and efficiency of estimates based on summarized data are
      compared to those based on individual-level data in simulation studies. We
      investigate the impact of gene-gene interactions, linkage disequilibrium, and
      'weak instruments' on these estimates. Both an inverse-variance weighted average
      of variant-specific associations and a likelihood-based approach for summarized
      data give similar estimates and precision to the two-stage least squares method
      for individual-level data, even when there are gene-gene interactions. However,
      these summarized data methods overstate precision when variants are in linkage
      disequilibrium. If the P-value in a linear regression of the risk factor for each
      variant is less than 1*10-5, then weak instrument bias will be small. We use
      these methods to estimate the causal association of low-density lipoprotein
      cholesterol (LDL-C) on coronary artery disease using published data on five
      genetic variants. A 30% reduction in LDL-C is estimated to reduce coronary artery
      disease risk by 67% (95% CI: 54% to 76%). We conclude that Mendelian
      randomization investigations using summarized data from uncorrelated variants are
      similarly efficient to those using individual-level data, although the necessary
      assumptions cannot be so fully assessed.

PMID- 24114803
TI  - Determination of doxorubicin in plasma by using CE coupled with in-column tapered
      optic-fiber light-emitting diode induced fluorescence detection.
AB  - This paper proposes a novel strategy to enhance detection of doxorubicin in human
      plasma, using homemade CE combined with normal stacking mode (NSM). The detection
      system of CE named as in-column tapered optic-fiber light-emitting diode induced
      fluorescence detection system is economic and more sensitive that has been
      demonstrated in our previous work. The influence of sample matrix, BGE, applied
      voltage, and injection time on the efficiency of NSM were systematically
      investigated. The clean extracts were subjected to CE separation with optimal
      experimental conditions: Ethanol-water (1:1, v/v) was used as sample matrix, pH
      4.12 15 mM sodium phosphate buffer solution containing 70% v/v ACN, applied
      voltage 23 kV and 45 s hydrodynamic injection at a height of 20 cm. The detection
      system displayed linear dynamic range from 6.4 to 1.13 * 10(3) ng/mL with a
      correlation coefficient of 0.9990 and LOD 2.2 ng/mL for doxorubicin (DOX). The
      proposed CE method has been successfully applied to determine DOX in human plasma
      which the recoveries of standard DOX added to human plasma were found to been the
      range of 93.8-104.6%. The results obtained demonstrate that our detection system
      combined with NSM is a good idea to enhance sensitivity in CE for routine
      determination of DOX in some biological specimens. 

PMID- 24114804
TI  - EACVI-ASE-industry initiative to standardize deformation imaging: a brief update
      from the co-chairs.

PMID- 24114806
TI  - The impact of imprisonment on overgeneral autobiographical memory in former
      political prisoners.
AB  - Traumatic experiences may dramatically influence later behavior and cognitive
      processing. This study investigated how trauma shapes the way that we remember
      personal experiences. Specifically, we investigated overgeneral autobiographical
      memory, which is the tendency to remember autobiographical events in an
      overgeneral rather than specific way. We administered the Autobiographical Memory
      Test (Williams & Broadbent,) to 86 survivors of political imprisonment 37 years
      after they had been released from imprisonment. Depression and posttraumatic
      stress disorder were not significantly related to overgeneral autobiographical
      memory. Significant overgeneral autobiographical memory correlates included
      embitterment, r = -.28, and being released to former East Germany, d = 0.67.
      Survivors with social support, r = .30 were better able to recall specific
      memories. Certain trauma characteristics and the way the trauma is processed may
      thus influence how personal memories are later remembered. This study also
      furthers the understanding of memory processes in political prisoners, who are
      not commonly studied in psychological research.

PMID- 24114805
TI  - The alpha2B-adrenergic receptor is mutant in cortical myoclonus and epilepsy.
AB  - OBJECTIVE: Autosomal dominant cortical myoclonus and epilepsy (ADCME) is
      characterized by distal, fairly rhythmic myoclonus and epilepsy with variable
      severity. We have previously mapped the disease locus on chromosome 2p11.1-q12.2
      by genome-wide linkage analysis. Additional pedigrees affected by similar forms
      of epilepsy have been associated with chromosomes 8q, 5p, and 3q, but none of the
      causing genes has been identified. We aim to identify the mutant gene responsible
      for this form of epilepsy. METHODS: Genes included in the ADCME critical region
      were directly sequenced. Coimmunoprecipitation, immunofluorescent, and
      electrophysiologic approaches to transfected human cells have been utilized for
      testing the functional significance of the identified mutation. RESULTS: Here we
      show that mutation in the alpha2 -adrenergic receptor subtype B (alpha2B -AR) is
      associated with ADCME by identifying a novel in-frame insertion/deletion in 2
      Italian families. The mutation alters several conserved residues of the third
      intracellular loop, hampering neither the alpha2B -AR plasma membrane
      localization nor the arrestin-mediated internalization capacity, but altering the
      binding with the scaffolding protein spinophilin upon neurotransmitter
      activation. Spinophilin, in turn, regulates interaction of G protein coupled
      receptors with regulator of G protein signaling proteins. Accordingly, the mutant
      alpha2B -AR increases the epinephrine-stimulated calcium signaling.
      INTERPRETATION: The identified mutation is responsible for ADCME, as the loss of
      alpha2B -AR/spinophilin interaction causes a gain of function effect. This work
      implicates for the first time the alpha-adrenergic system in human epilepsy and
      opens new ways of understanding the molecular pathway of epileptogenesis,
      widening the spectrum of possible therapeutic targets.

PMID- 24114807
TI  - Isolated X-linked hypertrophic cardiomyopathy caused by a novel mutation of the
      four-and-a-half LIM domain 1 gene.
AB  - BACKGROUND: Hypertrophic cardiomyopathy with severe left ventricular diastolic
      dysfunction has been associated with marked exercise intolerance and poor
      prognosis. However, molecular pathogenesis of this phenotype remains unexplained
      in a large proportion of cases. METHODS AND RESULTS: We performed whole exome
      sequencing as an initial genetic test in a large Czech family with 3 males
      affected by nonobstructive hypertrophic cardiomyopathy with severe left
      ventricular diastolic dysfunction in end-stage disease. A novel frameshift
      mutation of four-and-a-half LIM domain 1 gene (FHL1) (c.599_600insT; p.F200fs32X)
      was detected in these individuals. The mutation does not affect transcription,
      splicing, and stability of FHL1 mRNA and results in production of truncated FHL1
      protein, which is contrary to heart tissue homogenate not detectable in frozen
      tissue sections of myocardial biopsy of affected males. The identified mutation
      cosegregated also with abnormal ECG and with 1 case of apical hypertrophic
      cardiomyopathy in heterozygous females. Although skeletal muscle involvement is a
      common finding in FHL1-related diseases, we could exclude myopathy in all
      mutation carriers. CONCLUSIONS: We identified a novel FHL1 mutation causing
      isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.

PMID- 24114808
TI  - An introduction with medical applications to functional data analysis.
AB  - Functional data are data that can be represented by suitable functions, such as
      curves (potentially multi-dimensional) or surfaces. This paper gives an
      introduction to some basic but important techniques for the analysis of such
      data, and we apply the techniques to two datasets from biomedicine. One dataset
      is about white matter structures in the brain in multiple sclerosis patients; the
      other dataset is about three-dimensional vascular geometries collected for the
      study of cerebral aneurysms. The techniques described are smoothing, alignment,
      principal component analysis, and regression.

PMID- 24114809
TI  - Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular
      carcinoma: Evidence from a meta-analysis of individual participant data.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing in Western
      countries. Although several clinical factors have been identified, many
      individuals never develop HCC, suggesting a genetic susceptibility. However, to
      date, only a few single-nucleotide polymorphisms have been reproducibly shown to
      be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the
      PNPLA3 gene is associated with liver damage in chronic liver diseases.
      Interestingly, several studies have reported that the minor rs738409[G] allele is
      more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver
      disease (ALD). However, a significant association with HCC related to CHC has not
      been consistently observed, and the strength of the association between rs738409
      and HCC remains unclear. We performed a meta-analysis of individual participant
      data including 2,503 European patients with cirrhosis to assess the association
      between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was
      strongly associated with overall HCC (odds ratio [OR] per G allele, additive
      model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 * 10(-7) ). This
      association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 * 10(
      15) ) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 * 10(-2) ). After
      adjustment for age, sex, and body mass index, the variant remained strongly
      associated with HCC. CONCLUSION: Overall, these results suggest that rs738409
      exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of
      European descent and provide a strong argument for performing further mechanistic
      studies to better understand the role of PNPLA3 in HCC development.

PMID- 24114810
TI  - Orienting oxygen vacancies for fast catalytic reaction.
AB  - A strategy to enhance the catalytic activity at the surface of an oxide thin film
      is unveiled through epitaxial orientation control of the surface oxygen vacancy
      concentration. By tuning the direction of the oxygen vacancy channels (OVCs) in
      the brownmillerite SrCoO2.5 , a 100-fold improvement in the oxygen reduction
      kinetics is realized in an epitaxial thin film that has the OVCs open to the
      surface. 

PMID- 24114811
TI  - Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose
      escalation study to assess the safety and tolerability of topically applied AG013
      in subjects with locally advanced head and neck cancer receiving induction
      chemotherapy.
AB  - BACKGROUND: Oral mucositis (OM) is a significant toxicity of induction
      chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and
      tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis
      secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a
      phase 1b study in LAHNC subjects who received induction with cisplatin, 5
      fluorouracil, with or without docetaxel. Preliminary efficacy data were also
      obtained. METHODS: A total of 25 of 52 LAHNC subjects who were followed during
      induction cycle 1 developed ulcerative oral mucositis (UOM; World Health
      Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for
      cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 * 10(11) ,
      6 * 10(11) , and 1.2 * 10(12) colony forming units per day, respectively). OM was
      evaluated daily from cycle 2, day 1 through 14, using World Health Organization
      criteria. Pharmacokinetic assessment was also conducted. RESULTS: AG013 bacteria
      were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva
      and oral mucosa were equivalent among treatment groups. The most frequently
      occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal
      inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed
      to the investigational medicinal product: AG013 or placebo. Efficacy analysis
      showed a 35% reduction in percentage of days with UOM in AG013-subjects versus
      placebo. All placebo subjects experienced >= 2 days of UOM, whereas 29% of AG013
      subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office
      and emergency room visits. No differences were noted in mouth and throat
      soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS: AG013 was safe
      and well tolerated. Preliminary efficacy data support further study.

PMID- 24114812
TI  - Isolated myxoma of the external auditory canal.
AB  - The majority of neoplasms within the external auditory canal are benign.
      Management of these primary tumors and their local recurrences are discussed
      herein. We present a case of an isolated myxoma of the external auditory canal
      with a review of the common histopathological and radiographic features. Although
      rare, this highlights the possibility of encountering benign tumor types that
      carry associated morbidity or mortality due to manifestations outside of the head
      and neck.

PMID- 24114813
TI  - Treatment of chronic hepatitis C virus infection in the near future.

PMID- 24114814
TI  - Alcohol, liver and genes: an intricate puzzle.

PMID- 24114815
TI  - Hepatitis E virus: new faces of an old infection.
AB  - Hepatitis E virus is one of the most common causes of acute hepatitis worldwide,
      with the majority of cases occurring in Asia. In recent years, however, an
      increasing number of acute and chronic hepatitis E virus infections have been
      reported in industrialized countries. The importance of this infection resides in
      the associated morbidity and mortality. In acute cases, a high mortality rate has
      been reported in patients with previously undiagnosed alcoholic liver disease.
      Hepatitis E infection can become chronic in immunocompromised patients, such as
      solid organ transplant recipients, patients receiving chemotherapy, and HIV
      infected patients, and lead to the development of hepatic fibrosis and cirrhosis.
      Hence, treatment strategies involving reductions in immunosuppressive regimens
      and therapy with ribavirin or peg-interferon have been evaluated. In terms of
      prevention, a promising new vaccine was recently licensed in China, although its
      efficacy is uncertain and potential adverse effects in risk groups such as
      chronic liver disease patients and pregnant women require investigation. In
      conclusion, physicians should be aware of hepatitis E as a cause of both acute
      and chronic hepatitis in immunocompromised patients. The best treatment option
      for HEV infection remains to be defined, but both ribavirin and peg-interferon
      may have a role in therapy for this condition. 

PMID- 24114816
TI  - Prevalence of insulin resistance in chronic hepatitis C genotype 1 and 3
      patients.
AB  - BACKGROUND AND RATIONALE: Chronic infection with the hepatitis C virus (HCV) is
      associated with a higher prevalence of insulin resistance compared to the general
      population. This finding is associated with hepatic steatosis, increased liver
      fibrosis and lower rates of sustained virological response to interferon based
      therapy. The relationship of insulin resistance and HCV genotype is
      controversial. Our aim was to compare the prevalence of insulin resistance
      between patients with HCV genotype 1 and 3. The association of insulin
      resistance, hepatic steatosis and liver fibrosis was also investigated. RESULTS:
      Forty four consecutive treatment naive patients with HCV genotypes 1 or 3,
      without cirrhosis and without risk factors for metabolic syndrome were
      prospectively included. Insulin resistance was defined as a homeostasis model
      assessment for insulin resistance (HOMA-IR) above 2.0. Steatosis and fibrosis
      were assessed histologically. Insulin resistance was found in 27 (61%) patients
      and significant steatosis in 37 (84%) patients. Comparison between patients with
      HCV genotype 1 and 3 showed insulin resistance in 15 (65%) vs. 12 (57%),
      respectively (P = 0.81) and steatosis in 19 (83%) vs. 18 (86%), respectively (P =
      0.93). Comparison between patients with and without insulin resistance showed,
      respectively, a higher prevalence of significant fibrosis (56% vs. 6%; P =
      0.0001), and a higher mean degree of steatosis (1.3 +/- 0.72 vs. 0.76 +/- 0.56; P
      = 0.01). CONCLUSIONS: Prevalence of insulin resistance was not different between
      HCV infected patients with genotype 1 vs. 3. Nevertheless, independent of HCV
      genotype, there was a statistically significant relationship between insulin
      resistance and a higher amount of liver fibrosis and steatosis.

PMID- 24114817
TI  - Percutaneous liver biopsy--2 decades of experience in a public hospital in the
      South of Brazil.
AB  - INTRODUCTION: Liver biopsy is a complementary method for diagnosis, staging and
      therapeutic guidance in liver diseases, where chronic viral hepatitis are the
      most acknowledged causes for the indication of histopathological study. The
      objective is to assess the patients' profile as well as the indication and
      results of percutaneous liver biopsies in a tertiary hospital. MATERIAL AND
      METHODS: A descriptive, cross-section study was carried out through the review of
      medical charts (retrospective cohort) of patients submitted to blind percutaneous
      liver biopsies (PLB) at a hospital in Porto Alegre, South Brazil, from October
      1993 to December 2011. RESULTS: 1,955 PLB were carried out, the mean patients'
      age was 44.8 years old, and 1,127 (57.65%) were men. Chronic hepatitis C was the
      main indication (60.5%), followed by HCV-HIV coinfection (12.2%) and chronic
      hepatitis B (3.5%). Seven cases (0.3%) had complications, without deaths.
      CONCLUSION: PLB is a safe method and continues to be an important option to
      assist patients with chronic liver disease.

PMID- 24114818
TI  - Hormonal pretreatment preserves liver regenerative capacity and minimizes
      inflammation after partial hepatectomy.
AB  - INTRODUCTION: The treatment of brain dead donors with combined hormonal
      resuscitation protocols, including methylprednisolone (MP) and triiodothyronine
      (T3), among others, was developed to increase the viability and function of
      transplanted organs, primarily heart and lung. Even when it has regarded
      successful results in term of donors and organs recovery, its effects over
      specific parameters in organs like the liver are unknown. MATERIAL AND METHODS:
      Male Sprague-Dawley rats were pretreated with MP (0.34 mg/kg) and/or T3 (0.05
      mg/kg) or their vehicles, and then subjected to partial hepatectomy of 70%. Three
      experimental groups and their respective controls were conformed: a. T3; b. NaOH;
      c. MP; d. vMP; e. MP+T3 and f. vMP+NaOH. The groups were evaluated at 0, 16, 24,
      72 and 120 h post surgery. The effects of this protocol on regeneration, liver
      mass recovery, liver injury, oxidative stress and liver function were analyzed.
      RESULTS: MP+T3 pretreatment does not deleteriously affect liver regeneration
      after partial hepatectomy, as shown in the curve of total mass recovery, Ki67
      staining and mitosis counting, and does not alter liver function. In addition,
      the treatment modestly decreases oxidative stress and liver injury, as evidenced
      by transaminases levels, histological analysis and oxidized proteins content.
      CONCLUSION: These preclinical results indicate that MP+T3 is harmless for liver
      tissue regeneration post hepatectomy and additionally exhibits anti-inflammatory
      and antioxidant effects; therefore, it would not be contraindicated for the
      treatment of multiorgan donors in brain death and particularly, if the occurrence
      of small for size syndrome is suspected.

PMID- 24114819
TI  - Pioglitazone upregulates hepatic angiotensin converting enzyme 2 expression in
      rats with steatohepatitis.
AB  - OBJECTIVE: Angiotensin II, one component of renin-angiotensin system (RAS), is
      formed from Ang I by the catalysing of angiotensin converting enzyme (ACE).
      Angiotensin II plays an important role in the development of insulin resistance.
      ACE2, a homologue of ACE, couterregulate the actions of angiotensin II by
      facilitating its breakdown to angiotensin-(1-7). RAS has been implicated in the
      pathogenesis of non-alcoholic steatohepatitis (NASH). Earlier demonstration that
      thiazolidinediones (TZDs) improve steatohepatitis promoted us to evaluate the
      change of hepatic ACE2 expression in rats with high fat diet (HFD)-induced NASH
      and the effects of TZDs on the hepatic ACE2 expression. MATERIAL AND METHODS:
      Rats were divided into normal control group, high fat diet (HFD) group, and
      pioglitazone group. After 24 weeks of treatment with pioglitazone, a TZD, we
      evaluated changes in liver histology, insulin sensitivity, lipid metabolism,
      circulating RAS levels and hepatic ACE2 expression. RESULTS: Compared with normal
      controls, the concentrations of serum lipid, aminotransaminase, glucose, insulin,
      ACE, angiotensin II, ACE2, angiotensin-(1-7) and the degree of hepatic ACE2
      expression were significantly higher in rats with HFD-induced NASH. Pioglitazone
      significantly reduced the concentrations of serum lipid, aminotransaminase,
      glucose, insulin, ACE, angiotensin II while markedly raised the concentrations of
      serum ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression.
      CONCLUSION: Hepatic ACE2 expression markedly increased in rats with HFD-induced
      NASH and was further upregulated by pioglitazone. Hepatic ACE2 may be a new
      target of pioglitazone treatment for NASH.

PMID- 24114820
TI  - Genetic factors affecting susceptibility to alcoholic liver disease in an Indian
      population.
AB  - INTRODUCTION. Indians are more likely to develop alcoholic cirrhosis compared to
      Caucasians, though the cause remains obscure. North Indians tend to consume more
      alcohol than other parts of the country. Genetic factors are likely to play a
      major role in these observations. This study investigated whether 10 different
      polymorphisms were associated with alcohol dependence and/or cirrhosis in North
      Indians. These were in ADH2*2 (rs1229984), ADH3*2 (rs698), CYP2E1*1D, CYP2E1*5
      (rs3813867 and rs2031920), TNF-alpha(rs1800629), TNF-alpha (rs361525), IL-1beta
      (rs3087258), CD-14 (rs2569190), IL-10 (rs1800872) and PNPLA3 (rs738409). MATERIAL
      AND METHODS. Hundred healthy controls and 120 chronic alcoholics (60 alcoholic
      noncirrhotics and 60 alcoholic cirrhotics) attending various departments of
      PGIMER, Chandigarh were genotyped using PCR-RFLP methods. RESULTS. Alcoholic
      cirrhotics compared to healthy individuals demonstrated a statistically
      significant increase in PNPLA3 (10109G) allele (p = 0.037, OR = 2.12, 95% CI 1.29
      3.4). Rest of the associations were not significant after correction for multiple
      testing. CONCLUSION. PNPLA3 10109G predisposed North Indian subjects to alcoholic
      cirrhosis.

PMID- 24114821
TI  - Metabolic syndrome and nonalcoholic fatty liver disease. The role of endothelial
      progenitor cells.
AB  - BACKGROUND: Endothelial dysfunction has been previously described in metabolic
      syndrome patients. The levels of circulating endothelial progenitor cells (EPCs)
      inversely correlates with the incidence of cardiovascular disease. The aim of
      this study was to investigate the association between NAFLD, metabolic syndrome
      and EPC levels. MATERIAL AND METHODS: A cross-sectional pilot study was performed
      at a university hospital in Mexico. Two groups of patients without previously
      known chronic diseases were studied and classified according to the presence of
      NAFLD. Anthropometric, dietary, and biochemical variables, and circulating EPC
      number were measured and compared between the groups. RESULTS: Forty subjects
      were included and classified into two groups: patients with NAFLD (n = 20) and a
      control group (n = 20). The overall prevalence of insulin resistance and
      metabolic syndrome was 25% and 17.5%, respectively. EPC levels were found to be
      higher in the NAFLD group (p < 0.05) as in the patients with insulin resistance
      (p < 0.01) and metabolic syndrome (p < 0.01). These levels showed correlation
      with the severity of steatosis. CONCLUSIONS: Patients with NAFLD have increased
      levels of EPC, such levels are associated with the severity of NAFLD. These
      findings may suggest that these cells may play a role in the early natural
      history of NAFLD. EPC might be increased in an attempt to repair the endothelial
      damage resulting from metabolic alterations accompanying NAFLD. Further studies
      are needed to establish the dynamics of these cells in NAFLD.

PMID- 24114823
TI  - Noninvasive assessment of hepatic fibrosis using gadoxetate-disodium-enhanced 3T
      MRI.
AB  - INTRODUCTION: Gadoxetate-disodium is a liver-specific MR contrast agent absorbed
      by hepatocytes via organic anion transporting polypeptide 1B3 and is excreted
      into the biliary system by multidrug resistance-associated protein 2. It has been
      suggested that relative parenchymal enhancement on hepatocyte phase image is
      associated with hepatic function. However, it is not clear whether gadoxetate
      disodium-enhanced MRI can be used as a noninvasive fibrosis marker. Thus, the
      purpose of our study was to evaluate the diagnostic performance of gadoxetate
      disodium-enhanced MRI in predicting the hepatic fibrosis stage. MATERIALS AND
      METHODS: A total of 113 patients who had fibrosis staged according to the Batts
      and Ludwig score were enrolled: F0 (n = 13), F1 (n = 18), F2 (n = 15), F3 (n =
      32), and F4 (n = 35). All patients underwent gadoxetate-disodium-enhanced MRI
      before confirmation by biopsy (n = 67) or surgery (n = 46). For quantitative
      analysis, the contrast enhancement index (CEI) was calculated by measuring the
      signal intensity (SI) in liver and paraspinal muscle using a region of interest,
      as follows: CEI = (liver SI/paraspinal muscle SI) 20 min hepatocyte phase
      image/(liver SI/paraspinal muscle SI) pre-contrast T1-weighted image. The
      diagnostic performance was evaluated by the ROC curve, adjusted for the
      prevalence of each fibrosis stage. RESULTS: A significant negative correlation
      was observed between CEI and fibrosis stage (r = -0.545, P < 0.0001). The
      adjusted AUROC for CEI in the prediction of mild (>=?F1), moderate (>= F2), or
      severe fibrosis (>= F3) and liver cirrhosis (F4) was 0.668, 0.703, 0.73, and
      0.84, respectively. IN CONCLUSION: our results demonstrate that quantitative
      analysis of relative hepatic enhancement using gadoxetate-disodium-enhanced MRI
      can predict the hepatic fibrosis stage.

PMID- 24114822
TI  - Prognostic implication of serum vascular endothelial growth factor in advanced
      hepatocellular carcinoma staging.
AB  - BACKGROUND: Staging systems have considerable impact on hepatocellular carcinoma
      (HCC) treatment approaches and outcomes. There is an unmet need to improve their
      stratification ability. We have evaluated four commonly used staging systems and
      assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF)
      could improve their prognostic stratification. MATERIAL AND METHODS: Four staging
      systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic
      Liver Cancer (BCLC), and Child-Pugh were evaluated in 78 HCC patients; their
      stratification abilities were detected by Kaplan-Meier curves and log-rank test;
      their accuracies of predicting survival were compared with the concordance index.
      Serum VEGF levels were measured using ELISA method. Recursive partitioning was
      used to determine the optimal VEGF cutoff. The prognostic significance of VEGF
      cutoff and other parameters were analyzed using univariate and multivariate
      models. RESULTS: None of the staging systems demonstrated better discriminatory
      ability in predicting survival. The four staging systems did not reveal
      significant differences in probability of survival across their intermediate
      advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced
      HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were
      identified as the independent prognostic factors. Survival comparison with high
      and low VEGF levels was significant for advanced HCC, while insignificant for
      early disease. CONCLUSION: Staging systems with conventional parameters did not
      provide good prognostic stratification for survival in advanced HCC population.
      Serum VEGF level was an independent predictor of survival in advanced HCC, and
      provided more survival homogeneity within the advanced stages of conventional
      staging systems.

PMID- 24114824
TI  - ARFI cut-off values and significance of standard deviation for liver fibrosis
      staging in patients with chronic liver disease.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) elastometry quantifies
      hepatic stiffness, and thus degree of fibrosis, non-invasively. Our aim was to
      analyse the diagnostic accuracy of ARFI cut-off values, and the significance of a
      defined limit of standard deviation (SD) as a potential quality parameter for
      liver fibrosis staging in patients with chronic liver diseases (CLD). MATERIAL
      AND METHODS: 153 patients with CLD (various aetiologies) undergoing liver biopsy,
      and an additional 25 patients with known liver cirrhosis, were investigated. ARFI
      measurements were performed in the right hepatic lobe, and correlated with the
      histopathological Ludwig fibrosis score (inclusion criteria: at least 6 portal
      tracts). The diagnostic accuracy of cut-off values was analysed with respect to
      an SD limit of 30% of the mean ARFI value. RESULTS: The mean ARFI elastometry
      showed 1.95 +/- 0.87 m/s (range 0.79-4.40) in 178 patients (80 female, 98 male,
      mean age: 52 years). The cut-offs were 1.25 m/s for F >= 2, 1.72 m/s for F >= 3
      and 1.75 m/s for F = 4, and the corresponding AUROC 80.7%, 86.2% and 88.7%,
      respectively. Exclusion of 31 patients (17.4%) with an SD higher than 30% of the
      mean ARFI improved the diagnostic accuracy: The AUROC for F >= 2, F >= 3 and F =
      4 were 86.1%, 91.2% and 91.5%, respectively. CONCLUSION: The diagnostic accuracy
      of ARFI can be improved by applying a maximum SD of 30% of the mean ARFI as a
      quality parameter--which however leads to an exclusion of a relevant number of
      patients. ARFI results with a high SD should be interpreted with caution.

PMID- 24114825
TI  - Liver retransplantation in adults: a 20-year experience of one center in southern
      Brazil.
AB  - INTRODUCTION: Liver retransplantation (LReTx) is the therapeutic option for
      hepatic graft failure. Survival after LReTx is poorer than after primary liver
      transplantation. Given the organ shortage, it is essential to optimize the use of
      this resource. OBJECTIVE: To evaluate rates, indications and patient survival
      after LReTx and identify factors associated with mortality following LReTx.
      MATERIAL AND METHODS: We conducted a retrospective cohort study of all adults
      undergoing LReTx based on registry data from the Liver Transplantation Group
      (Complexo Hospitalar Santa Casa de Porto Alegre), southern Brazil. RESULTS:
      Between June 16, 1991 and July 19, 2011, 824 patients underwent 866 liver
      transplants. Forty-two procedures corresponded to LReTx (4.8% of all liver
      transplants performed). Thirty-eight patients who underwent a single LReTx
      procedure were included in this study. The leading indication for LReTx was
      hepatic artery thrombosis (HAT) (31.6%), followed by primary nonfunction (PNF)
      (18.4%). The main indication for early LReTx was PNF (58.3%) and for late LReTx
      was HAT (38.5%). During the follow-up period, 26 patients (68.4%) died after
      LReTx. Patient survival at 1 and 3 years after LReTx was 44.7% and 44.7%,
      respectively. Patients infected with hepatitis C virus, serum albumin < 2.5 g/dL
      and receiving mechanical ventilation immediately before LReTx had a significantly
      lower survival rate than the other patients. CONCLUSION: Considering the
      increased mortality when the graft loss is delayed, it is necessary to define the
      minimum acceptable results to indicate LReTx and identify the patients who would
      most benefit from this treatment.

PMID- 24114826
TI  - Impact of untreated portal vein thrombosis on pre and post liver transplant
      outcomes in cirrhosis.
AB  - BACKGROUND AND AIMS: Most portal vein thromboses (PVT) in cirrhotics are
      discovered incidentally. While case series demonstrate improved portal vein
      patency with anti-coagulation, there is little information on impact of PVT on
      morbidity and mortality. This study aimed to compare morbidity and mortality in
      cirrhotics with untreated PVT with those without PVT. MATERIAL AND METHODS:
      Cirrhotics evaluated for orthotopic liver transplant in a single large transplant
      center were prospectively followed. Subjects had contrast CT or MRI at initial
      evaluation and serial imaging every 6 months until transplantation, removal from
      the list or death. Univariate and multivariate Cox regression analysis were used
      to assess associations between new PVT and factors of interest. RESULTS: Of the
      290 prospectively followed cirrhotics who met inclusion criteria, PVT was
      detected in 70 (24.1%)-47 had PVT at the time of initial evaluation and 23
      developed one during the pre-transplant study period. A third of the patients
      with PVT had re-canalization or spontaneous resolution of thrombus while awaiting
      transplantation. There was no difference in the pre or posttransplant mortality
      between cirrhotics with and without PVT. CONCLUSION: Cirrhotics with untreated
      PVT fared equally well as those without PVT before and after transplantation.
      Further studies with larger numbers of patients are needed to determine if
      anticoagulation therapy truly improves outcomes in cirrhotics with portal vein
      thrombosis.

PMID- 24114827
TI  - Association of GST null genotypes with anti-tuberculosis drug induced
      hepatotoxicity in Western Indian population.
AB  - BACKGROUND: The first line anti-tubercular (anti-TB) treatment normally involves
      isoniazid, rifampicin, pyrazinamide, and ethambutol. Clearance of these drugs
      depends on the activity of several enzymes such as N-acetyl transferase 2,
      cytochrome P450 oxidase and glutathione S-transferase (GST). Some of these
      enzymes are highly polymorphic leading to significant inter-individual variation
      in their activity thereby increasing the risk of drug induced hepatotoxicity
      (DIH). AIM: To investigate the possible association of anti-TB DIH with genetic
      polymorphism of GST genes in Western Indian population. MATERIAL AND METHODS: A
      prospective case-control study was undertaken on patients who received anti-TB
      treatment. Cases (n = 50) were distinguished from controls (n = 246) based on
      occurrence of DIH during anti-tubercular treatment. A multiplex polymerase chain
      reaction was employed to identify homozygous null mutation at GSTM1 and GSTT1
      loci. Results. Homozygous null mutation in GSTM1 gene alone or in both GSTM1 and
      T1 genes was found to be significantly associated with anti-TB DIH at p < 0.02
      and p < 0.007, respectively, in our study population. CONCLUSIONS: This is the
      first study to report GSTM1 null and combined GSTM1 and T1 null genotypes to be
      risk factors of anti-TB DIH in Western Indian population. Screening of patients
      for these genotypes prior to anti-TB regimen would provide better control of
      hepatotoxicity.

PMID- 24114828
TI  - Hepatolithiasis with secondary cholangitis and supernumerary left hepatic lobe.
AB  - We report the case of a 31-year old woman with recurrent cholangitis secondary to
      hepatolithiasis. The stones were composed of calcium bilirubinate. The patient
      also had a supernumerary hepatic lobe connected to the inferior aspect of the
      segment III of the liver. The role of the supernumerary hepatic lobe in the
      development of hepatolithiasis is unclear and may be coincidental.

PMID- 24114829
TI  - Portal venous tumor growth-type of hepatocellular carcinoma without liver
      parenchyma tumor nodules: a case report.
AB  - The patient was a 43-year-old man with chronic hepatitis B without history of
      hepatocellular carcinoma (HCC), who was first diagnosed with thrombosis in right
      portal vein trunk and portal vein branches and ruptured esophageal varices in
      October 2011. He underwent endoscopic variceal ligation, but ruptured repeatedly.
      Despite anti-coagulant therapy, the thrombosis expanded from right portal vein
      trunk to upper mesenteric vein in March 2012. Computed tomography (CT) scan
      showed that portal vein thrombosis had low density from early to late phase. No
      focal liver lesions were identified by CT scan or ultrasound, and alpha
      fetoprotein (AFP) was within normal range. He died by intractable esophageal
      variceal bleeding in April 2012. Pathological examination of autopsy specimen
      showed that portal vein thrombosis was consistent with poorly-differentiated HCC.
      The portal vein tumor thrombosis (PVTT) had only a few tumor vessels, which were
      compressed by fibromatous change originating from HCC formation, so were
      represented as low-density lesions from arterial to portal phase of CT. In
      addition, PVTT was negative for AFP, so representing serum value of AFP within
      normal range. PVTT had positive staining for c-kit, which is a liver stem cell
      marker. Liver tumors in the whole liver parenchyma were not found pathologically.
      PVTT might have the characteristics of presumed liver cancer stem cells. We
      experienced the first case of HCC only in portal vein without liver parenchyma
      tumor nodules, with difficult differential diagnosis from a non-malignant portal
      vein thrombosis. We also reported new tumor profiles of the portal venous tumor
      growth- type of HCC. 

PMID- 24114831
TI  - Giant biliary mucinous cystadenoma of the liver.
AB  - Biliary mucinous cystadenomas (BMC) of the liver are rare benign cystic tumors,
      however an estimated 20% undergo malignant transformation. They have recently
      been redefined as mucinous cystic neoplasms in the 2010 WHO classification. The
      preferred treatment is through radical resection, as there are high recurrence
      rates with other treatment modalities; however this is often not possible in
      patients with bilobar or giant cysts, and liver transplantation may be indicated.
      We present a patient with a giant biliary mucinous cystadenoma of the liver and
      discuss the management with reference to the literature. A 47 year-old woman
      presented with a 6-week history of moderate epigastric discomfort on a background
      of 12 months of symptom-free abdominal distension. A giant cystic bilobar tumor
      of the liver measuring 22 x 23 x 17 cm was diagnosed and characterised by
      ultrasound scan and magnetic resonance imaging. Serum bilirubin, alkaline
      phosphatase and gamma-glutamyl transpeptidase were elevated, though other
      laboratory data including tumor markers (CEA, aFP, CA19-9) were within normal
      limits. Total excision of the cyst was not possible due to its size and position,
      and the patient underwent cyst drainage, a sub-total cyst excision and
      omentoplasty. Histology confirmed a benign biliary mucinous cystadenoma with an
      ovarian stroma. Though the patient remained clinically well, routine post
      operative computed tomography (CT) surveillance showed an 11 cm recurrent cyst at
      6 months. A partial cyst resection with close follow-up, regular CA19-9 serology
      and ultrasound/CT imaging, may be a reasonable alternative for bilobar or giant
      cysts. However should any features pathognomonic of malignancy develop, then a
      liver transplantation is indicated. 

PMID- 24114830
TI  - Haemophagocytic syndrome in a liver transplant patient during treatment with
      Telaprevir.
AB  - Haemophagocytic syndrome (HS) is a rare disease that is often fatal despite
      treatment. HS is characterized by fevers, lymphadenopathy, hepatosplenomegaly,
      cytopenias and hyperferritinaemia due to deregulated activation and proliferation
      of macrophages, leading to uncontrolled phagocytosis of platelets, erythrocytes,
      lymphocytes, and their hematopoietic precursors throughout the
      reticuloendothelial system. Mycobacterium tuberculosis-associated HS is a rare
      and underdiagnosed association with only 39 cases reported. We describe a case of
      HS associated with disseminated Mycobacterium tuberculosis in the setting of post
      liver transplantation anti-hepatitis C therapy with pegylated interferon
      (pegIFN), ribavirin (RBV) and telaprevir (TVR). Despite the delay in the
      etiologic diagnosis, the patient was treated properly with corticosteroids,
      cyclosporine and tuberculostatic agents. It is unknown whether telaprevir, a drug
      that only recently has been started off-label in liver transplant recipients, may
      have contributed to the development of the HS. Unfortunately, as in many reported
      cases of HS, the outcome was unfavourable resulting in the death of the patient. 

PMID- 24114832
TI  - Defining renal failure in cirrhosis--acute kidney injury classification or
      traditional criteria?

PMID- 24114833
TI  - Experimental design in formulation of diazepam nanoemulsions: physicochemical and
      pharmacokinetic performances.
AB  - With the aid of experimental design, we developed and characterized nanoemulsions
      for parenteral drug delivery. Formulations containing a mixture of medium-chain
      triglycerides and soybean oil as oil phase, lecithin (soybean/egg) and
      polysorbate 80 as emulsifiers, and 0.1 M phosphate buffer solution (pH 8) as
      aqueous phase were prepared by cold high-pressure homogenization. To study the
      effects of the oil content, lecithin type, and the presence of diazepam as a
      model drug and their interactions on physicochemical characteristics of
      nanoemulsions, a three factor two-level full factorial design was applied. The
      nanoemulsions were evaluated concerning droplet size and size distribution,
      surface charge, viscosity, morphology, drug-excipient interactions, and physical
      stability. The characterization revealed the small spherical droplets in the
      range 195 -220 nm with polydispersity index below 0.15 and zeta potential between
      -30 and - 60 mV. Interactions among the investigated factors, rather than factors
      alone, were shown to more profoundly affect nanoemulsion characteristics. In vivo
      pharmacokinetic study of selected diazepam nanoemulsions with different oil
      content (20%, 30%, and 40%, w/w) demonstrated fast and intense initial
      distribution into rat brain of diazepam from nanoemulsions with 20% and 30% (w/w)
      oil content, suggesting their applicability in urgent situations.

PMID- 24114834
TI  - Protective effect of dexmedetomidine on noise-induced hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: Noise generated by instruments, such as mastoid or
      craniotomy drills, may cause hearing damage by reducing the cochlear blood flow
      (CoBF). This study investigated whether dexmedetomidine can lessen noise-induced
      hearing loss (NIHL) in a guinea pig model. STUDY DESIGN: Animal study using noise
      stimulation and measurement of hearing and CoBF in guinea pigs. METHODS: Guinea
      pigs (n = 8 animals/group) were treated by saline vehicle (control group),
      dexmedetomidine (1, 3, and 10 MUg/kg dex groups), saline and noise (noise group),
      or 3 MUg/kg dexmedetomidine and noise (dex+noise group). For noise exposure,
      octave band noise at 124 dB sound pressure level was administered to animals for
      2 hours. Blood pressure (BP) and CoBF were monitored continuously. Auditory
      function was measured by the auditory brain-stem response (ABR) before and 1
      hour, 3 hours, 8 hours, and 10 days after noise exposure. Plasma norepinephrine
      (NE) was measured at baseline and 30, 60, 90, and 120 minutes after noise
      exposure by high-performance liquid chromatography (HPLC). RESULTS: Noise
      exposure caused temporary and permanent hearing damage. Dexmedetomidine
      concentrations of 1 MUg/kg and 3 MUg/kg dose dependently improved CoBF.
      Administration of 10 MUg/kg dexmedetomidine drastically reduced BP and CoBF.
      Pretreatment with 3 MUg/kg dexmedetomidine alleviated the noise-induced reduction
      in CoBF and improved hearing function by decreasing the permanent and temporary
      threshold shifts. CONCLUSION: Dexmedetomidine displayed protective effects
      against NIHL in this animal model, suppressing activation of the sympathetic
      nervous system and improving CoBF. These findings could have clinical relevance
      and deserve further investigation.

PMID- 24114835
TI  - Chiral primary-amine-catalyzed conjugate addition to alpha-substituted vinyl
      ketones/aldehydes: divergent stereocontrol modes on enamine protonation.
AB  - Enantioselective protonation with a catalytic enamine intermediate represents a
      challenging, yet fundamentally important process for the synthesis of alpha
      chiral carbonyls. We describe herein chiral primary-amine-catalyzed conjugate
      additions of indoles to both alpha-substituted acroleins and vinyl ketones. These
      reactions feature enamine protonation as the stereogenic step. A simple primary
      tertiary vicinal diamine 1 with trifluoromethanesulfonic acid (TfOH) was found to
      enable both of the reactions of acroleins and vinyl ketones with good activity
      and high enantioselectivity. Detailed mechanistic studies reveal that these
      reactions are rate-limiting in iminium formation and they all involve a uniform
      H2 O/acid-bridged proton transfer in the stereogenic steps but divergent
      stereocontrol modes for the protonation stereoselectivity. For the reactions of
      alpha-branched acroleins, facial selections on H2 O-bridged protonation determine
      the enantioselectivity, which is enhanced by an OH???pi interaction with indole
      as uncovered by DFT calculations. On the other hand, the stereoselectivity of the
      reactions with vinyl ketones is controlled according to the Curtin-Hammett
      principle in the C?C bond-formation step, which precedes a highly stereospecific
      enamine protonation. 

PMID- 24114836
TI  - The structure of irisin reveals a novel intersubunit beta-sheet fibronectin type
      III (FNIII) dimer: implications for receptor activation.
AB  - Irisin was recently identified as a putative myokine that is induced by exercise.
      Studies suggest that it is produced by cleavage of the FNDC5 (fibronectin domain
      containing protein 5) receptor; irisin corresponds to the extracellular receptor
      ectodomain. Data suggesting that irisin stimulates white-to-brown fat conversion
      have led to the hypothesis that it does so by binding an unknown receptor, thus
      functioning as a myokine. As brown fat promotes energy dissipation, myokines that
      elicit the transformation of white to brown fat have potentially profound
      benefits in the treatment of obesity and metabolic disorders. Understanding the
      molecular basis for such exercise-induced phenomena is thus of considerable
      interest. Moreover, FNDC5-like receptors are highly conserved and have been shown
      to be critical for neuronal development. However, the structural and molecular
      mechanisms utilized by these proteins are currently unknown. Here, we describe
      the crystal structure and biochemical characterization of the FNDC5 ectodomain,
      corresponding to the irisin myokine. The 2.28 A structure shows that irisin
      consists of an N-terminal fibronectin III (FNIII)-like domain attached to a
      flexible C-terminal tail. Strikingly, the FNIII-like domain forms a continuous
      intersubunit beta-sheet dimer, previously unobserved for any FNIII protein.
      Biochemical data confirm that irisin is a dimer and that dimerization is
      unaffected by glycosylation. This finding suggests a possible mechanism for
      receptor activation by the irisin domain as a preformed myokine dimer ligand or
      as a paracrine or autocrine dimerization module on FNDC5-like receptors. 

PMID- 24114837
TI  - Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4) is an acidocalcisome
      polyphosphate kinase required for in vivo infection.
AB  - Polyphosphate (polyP) is an anionic polymer of orthophosphate groups linked by
      high energy bonds that typically accumulates in acidic, calcium-rich organelles
      known as acidocalcisomes. PolyP synthesis in eukaryotes was unclear until it was
      demonstrated that the protein named Vtc4p (vacuolar transporter chaperone 4) is a
      long chain polyP kinase that localizes to the yeast vacuole. Here, we report that
      TbVtc4 (Vtc4 ortholog of Trypanosoma brucei) encodes, in contrast, a short chain
      polyP kinase that localizes to acidocalcisomes. The subcellular localization of
      TbVtc4 was demonstrated by fluorescence and electron microscopy of cell lines
      expressing TbVtc4 in its endogenous locus fused to an epitope tag and by purified
      polyclonal antibodies against TbVtc4. Recombinant TbVtc4 was expressed in
      bacteria, and polyP kinase activity was assayed in vitro. The in vitro growth of
      conditional knock-out bloodstream form trypanosomes (TbVtc4-KO) was significantly
      affected relative to the parental cell line. This mutant had reduced polyP kinase
      activity and short chain polyP content and was considerably less virulent in
      mice. The wild-type phenotype was recovered when an ectopic copy of the TbVtc4
      gene was expressed in the presence of doxycycline. The mutant also exhibited a
      defect in volume recovery under osmotic stress conditions in vitro, underscoring
      the relevance of polyP in osmoregulation. 

PMID- 24114838
TI  - Insulin secretion and Ca2+ dynamics in beta-cells are regulated by PERK (EIF2AK3)
      in concert with calcineurin.
AB  - Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) (EIF2AK3) is
      essential for normal development and function of the insulin-secreting beta-cell.
      Although genetic ablation of PERK in beta-cells results in permanent neonatal
      diabetes in humans and mice, the underlying mechanisms remain unclear. Here, we
      used a newly developed and highly specific inhibitor of PERK to determine the
      immediate effects of acute ablation of PERK activity. We found that inhibition of
      PERK in human and rodent beta-cells causes a rapid inhibition of secretagogue
      stimulated subcellular Ca(2+) signaling and insulin secretion. These dysfunctions
      stem from alterations in store-operated Ca(2+) entry and sarcoplasmic endoplasmic
      reticulum Ca(2+)-ATPase activity. We also found that PERK regulates calcineurin,
      and pharmacological inhibition of calcineurin results in similar defects on
      stimulus-secretion coupling. Our findings suggest that interplay between
      calcineurin and PERK regulates beta-cell Ca(2+) signaling and insulin secretion,
      and that loss of this interaction may have profound implications in insulin
      secretion defects associated with diabetes. 

PMID- 24114839
TI  - Protein kinase PKN1 represses Wnt/beta-catenin signaling in human melanoma cells.
AB  - Advances in phosphoproteomics have made it possible to monitor changes in protein
      phosphorylation that occur at different steps in signal transduction and have
      aided the identification of new pathway components. In the present study, we
      applied this technology to advance our understanding of the responses of melanoma
      cells to signaling initiated by the secreted ligand WNT3A. We started by
      comparing the phosphopeptide patterns of cells treated with WNT3A for different
      periods of time. Next, we integrated these data sets with the results from a
      siRNA screen that targeted protein kinases. This integration of siRNA screening
      and proteomics enabled us to identify four kinases that exhibit altered
      phosphorylation in response to WNT3A and that regulate a luciferase reporter of
      beta-catenin-responsive transcription (beta-catenin-activated reporter). We
      focused on one of these kinases, an atypical PKC kinase, protein kinase N1
      (PKN1). Reducing the levels of PKN1 with siRNAs significantly enhances activation
      of beta-catenin-activated reporter and increases apoptosis in melanoma cell
      lines. Using affinity purification followed by mass spectrometry, we then found
      that PKN1 is present in a protein complex with a WNT3A receptor, Frizzled 7, as
      well as with proteins that co-purify with Frizzled 7. These data establish that
      the protein kinase PKN1 inhibits Wnt/beta-catenin signaling and sensitizes
      melanoma cells to cell death stimulated by WNT3A. 

PMID- 24114840
TI  - 17beta-Estradiol inhibits phosphorylation of stromal interaction molecule 1
      (STIM1) protein: implication for store-operated calcium entry and chronic lung
      diseases.
AB  - Sex plays a significant role in the development of lung diseases including
      asthma, cancer, chronic bronchitis, and cystic fibrosis. In cystic fibrosis,
      17beta-estradiol (E2) may inhibit store-operated Ca(2+) entry (SOCE) to impinge
      upon airway secretions, leaving females at greater risk of contracting lung
      infections. Stromal interaction molecule 1 (STIM1)-mediated SOCE is essential for
      cell homeostasis and regulates numerous processes including cell proliferation,
      smooth muscle contraction, and secretion. E2 can signal nongenomically to
      modulate Ca(2+) signaling, but little is known of the underlying mechanisms. We
      found that E2 exposure inhibited STIM1 translocation in airway epithelia,
      preventing SOCE. This correlated with a decrease in STIM1-STIM1 FRET and STIM1
      mobility in E2-exposed HEK293T cells co-expressing estrogen receptor alpha. We
      also examined the role of STIM1 phosphorylation in E2-mediated inhibition of
      STIM1 mobility. STIM1 is basally phosphorylated at serine 575, which is required
      for SOCE. Exposure to E2 significantly decreased STIM1 serine phosphorylation.
      Mutating serine 575 to an alanine blocked STIM1 phosphorylation, reduced basal
      STIM1 mobility, and rendered STIM1 insensitive to E2. These data indicate that E2
      can signal nongenomically by inhibiting basal phosphorylation of STIM1, leading
      to a reduction in SOCE. 

PMID- 24114841
TI  - Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK)
      activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6)
      self-association leading to transforming growth factor beta-activated kinase 1
      (TAK1) recruitment.
AB  - Vaccinia virus encodes a number of proteins that inhibit and manipulate innate
      immune signaling pathways that also have a role in virulence. These include A52,
      a protein shown to inhibit IL-1- and Toll-like receptor-stimulated NFkappaB
      activation, via interaction with interleukin-1 receptor-associated kinase 2
      (IRAK2). Interestingly, A52 was also found to activate p38 MAPK and thus enhance
      Toll-like receptor-dependent IL-10 induction, which was TRAF6-dependent, but the
      manner in which A52 manipulates TRAF6 to stimulate p38 activation was unclear.
      Here, we show that A52 has a non-canonical TRAF6-binding motif that is essential
      for TRAF6 binding and p38 activation but dispensable for NFkappaB inhibition and
      IRAK2 interaction. Wild-type A52, but not a mutant defective in p38 activation
      and TRAF6 binding (F154A), caused TRAF6 oligomerization and subsequent TRAF6-TAK1
      association. The crystal structure of A52 shows that it adopts a Bcl2-like fold
      and exists as a dimer in solution. Residue Met-65 was identified as being located
      in the A52 dimer interface, and consistent with that, A52-M65E was impaired in
      its ability to dimerize. A52-M65E although capable of interacting with TRAF6, was
      unable to cause either TRAF6 self-association, induce the TRAF6-TAK1 association,
      or activate p38 MAPK. The results suggest that an A52 dimer causes TRAF6 self
      association, leading to TAK1 recruitment and p38 activation. This reveals a
      molecular mechanism whereby poxviruses manipulate TRAF6 to activate MAPKs (which
      can be proviral) without stimulating antiviral NFkappaB activation. 

PMID- 24114843
TI  - Different Raf protein kinases mediate different signaling pathways to stimulate
      E3 ligase RFFL gene expression in cell migration regulation.
AB  - We previously characterized a Galpha12-specific signaling pathway that stimulates
      the transcription of the E3 ligase RFFL via the protein kinase ARAF and ERK. This
      pathway leads to persistent PKC activation and is important for sustaining
      fibroblast migration. However, questions remain regarding how Galpha12
      specifically activates ARAF, which transcription factor is involved in Galpha12
      mediated RFFL expression, and whether RFFL is important for cell migration
      stimulated by other signaling mechanisms that can activate ERK. In this study, we
      show that replacement of the Galpha12 residue Arg-264 with Gln, which is the
      corresponding Galpha13 residue, abrogates the ability of Galpha12 to interact
      with or activate ARAF. We also show that Galpha12 can no longer interact with and
      activate an ARAF mutant with its C-terminal sequence downstream of the kinase
      domain being replaced with the corresponding CRAF sequence. These results explain
      why Galpha12, but not Galpha13, specifically activates ARAF but not CRAF.
      Together with our finding that recombinant Galpha12 is sufficient for stimulating
      the kinase activity of ARAF, this study reveals an ARAF activation mechanism that
      is different from that of CRAF. In addition, we show that this Galpha12-ARAF-ERK
      pathway stimulates RFFL transcription through the transcription factor c-Myc. We
      further demonstrate that EGF, which signals through CRAF, and an activated BRAF
      mutant also activate PKC and stimulate cell migration through up-regulating RFFL
      expression. Thus, RFFL-mediated PKC activation has a broad significance in cell
      migration regulation. 

PMID- 24114844
TI  - Endoplasmic reticulum-associated degradation controls cell surface expression of
      gamma-aminobutyric acid, type B receptors.
AB  - Metabotropic GABAB receptors are crucial for controlling the excitability of
      neurons by mediating slow inhibition in the CNS. The strength of receptor
      signaling depends on the number of cell surface receptors, which is thought to be
      regulated by trafficking and degradation mechanisms. Although the mechanisms of
      GABAB receptor trafficking are studied to some extent, it is currently unclear
      whether receptor degradation actively controls the number of GABAB receptors
      available for signaling. Here we tested the hypothesis that proteasomal
      degradation contributes to the regulation of GABAB receptor expression levels.
      Blocking proteasomal activity in cultured cortical neurons considerably enhanced
      total and cell surface expression of GABAB receptors, indicating the constitutive
      degradation of the receptors by proteasomes. Proteasomal degradation required
      Lys(48)-linked polyubiquitination of lysines 767/771 in the C-terminal domain of
      the GABAB2 subunit. Inactivation of these ubiquitination sites increased receptor
      levels and GABAB receptor signaling in neurons. Proteasomal degradation was
      mediated by endoplasmic reticulum-associated degradation (ERAD) as shown by the
      accumulation of receptors in the endoplasmic reticulum upon inhibition of
      proteasomes, by the increase of receptor levels, as well as receptor signaling
      upon blocking ERAD function, and by the interaction of GABAB receptors with the
      essential ERAD components Hrd1 and p97. In conclusion, the data support a model
      in which the fraction of GABAB receptors available for plasma membrane
      trafficking is regulated by degradation via the ERAD machinery. Thus, modulation
      of ERAD activity by changes in physiological conditions may represent a mechanism
      to adjust receptor numbers and thereby signaling strength. 

PMID- 24114845
TI  - Prediction of essential oil content of oregano by hand-held and Fourier transform
      NIR spectroscopy.
AB  - BACKGROUND: In the framework of a breeding programme, the analysis of hundreds of
      oregano samples to determine their essential oil content (EOC) is time-consuming
      and expensive in terms of labour. Therefore developing a new method that is
      rapid, accurate and less expensive to use would be an asset to breeders. The aim
      of the present study was to develop a method based on near-inrared (NIR)
      spectroscopy to determine the EOC of oregano dried powder. Two spectroscopic
      approaches were compared, the first using a hand-held NIR device and the second a
      Fourier transform (FT) NIR spectrometer. RESULTS: Hand-held NIR (1000-1800 nm)
      measurements and partial least squares regression allowed the determination of
      EOC with R2 and SEP values of 0.58 and 0.81 mL per 100 g dry matter (DM)
      respectively. Measurements with FT-NIR (1000-2500 nm) allowed the determination
      of EOC with R2 and SEP values of 0.91 and 0.68 mL per 100 g DM respectively. RPD,
      RER and RPIQ values for the model implemented with FT-NIR data were satisfactory
      for screening application, while those obtained with hand-held NIR data were
      below the level required to consider the model as enough accurate for screening
      application. CONCLUSION: The FT-NIR approach allowed the development of an
      accurate model for EOC prediction. Although the hand-held NIR approach is
      promising, it needs additional development before it can be used in practice.

PMID- 24114842
TI  - The antiparasitic clioquinol induces apoptosis in leukemia and myeloma cells by
      inhibiting histone deacetylase activity.
AB  - The antiparasitic clioquinol (CQ) represents a class of novel anticancer drugs by
      interfering with proteasome activity. In the present study, we found that CQ
      induced blood cancer cell apoptosis by inhibiting histone deacetylases (HDACs).
      CQ accumulated the acetylation levels of several key proteins including histone
      H3 (H3), p53, HSP90, and alpha-tubulin. In the mechanistic study, CQ was found to
      down-regulate HDAC1, -3, -4, and -5 in both myeloma and leukemia cells. Computer
      modeling analysis revealed that CQ was well docked into the active pocket of the
      enzyme, where the oxygen and nitrogen atoms in CQ formed stable coordinate bonds
      with the zinc ion, and the hydroxyl group from CQ formed an effective hydrogen
      bond with Asp-267. Moreover, co-treatment with CQ and zinc/copper chloride led to
      decreased Ac-H3. Furthermore, CQ inhibited the activity of Class I and IIa HDACs
      in the cell-free assays, demonstrating that CQ interfered with HDAC activity. By
      inhibiting HDAC activity, CQ induced expression of p21, p27, and p53, cell cycle
      arrest at G1 phase, and cell apoptosis. This study suggested that the HDAC
      enzymes are targets of CQ, which provided a novel insight into the molecular
      mechanism of CQ in the treatment of hematological malignancies. 

PMID- 24114847
TI  - Developments in coupled solid-phase extraction-capillary electrophoresis 2011
      2013.
AB  - This article presents an overview of the design and application of coupled SPE-CE
      systems that have been reported in the literature between January 2011 and June
      2013. The present paper is an update of three previous review papers covering the
      years 2000-2011 (Electrophoresis 2008, 29, 108-128; Electrophoresis 2010, 31, 44
      54; Electrophoresis 2012, 33, 243-250). The use of in-line and on-line SPE-CE
      approaches is described in this review. Emerging technological developments, such
      as the use of in-line frit-free SPE and chip-based SPE for extraction of sample
      components prior to CE analysis, are outlined. Selected examples illustrate the
      applicability of SPE-CE in biomedical, pharmaceutical, and environmental
      analysis. A complete overview of recent SPE-CE studies is given in table format,
      providing information on sample type, SPE sorbent, coupling mode, detection mode,
      and LOD. Finally, some general conclusions and future perspectives are provided.

PMID- 24114846
TI  - A multifaith spiritually based intervention versus supportive therapy for
      generalized anxiety disorder: a pilot randomized controlled trial.
AB  - OBJECTIVES: We have previously reported that a multifaith spiritually based
      intervention (SBI) may have efficacy in the treatment of generalized anxiety
      disorder (GAD). This randomized pilot trial tested whether the SBI had greater
      efficacy than a nonspecific control condition in GAD. METHOD: Twenty-three
      participants with GAD of at least moderate severity were randomized to 12
      individual sessions of the SBI (n = 11) or supportive psychotherapy (SP)--our
      control condition (n = 12). RESULTS: Intent-to-treat analysis revealed the SBI
      fared better than SP in decreasing blind clinician ratings of anxiety and illness
      severity and self-report worry and intolerance of uncertainty, with large between
      group effect sizes. The SBI also produced greater changes in spiritual well
      being. Results remained the same when supplementary analyses were performed on
      the completer sample. Treatment gains were maintained at 3-months follow-up.
      CONCLUSIONS: This small pilot trial demonstrates that a nondenominational SBI has
      greater efficacy than a rigorous control in improving symptoms of GAD and
      enhancing spiritual well-being. These results are encouraging and further
      research on the efficacy of the SBI and its underlying mechanisms is warranted.

PMID- 24114849
TI  - Susceptibility to cytomegalovirus, parvovirus B19 and age-dependent differences
      in levels of rubella antibodies among pregnant women.
AB  - Infections caused by cytomegalovirus (CMV), parvovirus B19 (B19), and rubella can
      lead to serious complications in pregnant women. The aim of this study was to
      determine the susceptibility to CMV, B19, and rubella antibodies in pregnant
      women in Norway. Consecutive sera samples were collected from pregnant women in
      two different regions in Norway. Sera were collected from age groups; <=19, 20
      24, 25-29, 30-34, 35-39, and >=40 years old. Of the 2,000 pregnant women tested,
      anti-CMV IgG was positive in 62.8% anti-parvovirus B19 IgG in 59.7% and anti
      rubella IgG in 94.4%. CMV IgG susceptibility has decreased in pregnant women less
      than 30 years of age, from 60% in a study conducted in 1973-1974 to 37.2% in
      present study. There was a significant difference in CMV IgG seropositivity rate
      between the two regions (58.6% and 67.1%). Serum levels of rubella IgG was lowest
      in age group 25-29 years with a positivity rate of 91.0%. Women born before
      vaccination with two doses of MMR started, had both a higher positivity rate and
      significantly higher levels of rubella antibody titre, 96.1% and 82.2 IU/ml
      compared to those born after 92.9% and 41.7 IU/ml. Significantly lower anti
      rubella IgG titre found in the youngest age groups highlights the need for
      continued antenatal screening. A considerable increase in anti-CMV-IgG
      seropositivity rate was observed and might be associated with higher rate of
      breastfeeding and a higher percentage attending day-care centres.

PMID- 24114848
TI  - A whole-genome simulator capable of modeling high-order epistasis for complex
      disease.
AB  - Genome-wide association studies (GWAS) have been successful in finding numerous
      new risk variants for complex diseases, but the results almost exclusively rely
      on single-marker scans. Methods that can analyze joint effects of many variants
      in GWAS data are still being developed and trialed. To evaluate the performance
      of such methods it is essential to have a GWAS data simulator that can rapidly
      simulate a large number of samples, and capture key features of real GWAS data
      such as linkage disequilibrium (LD) among single-nucleotide polymorphisms (SNPs)
      and joint effects of multiple loci (multilocus epistasis). In the current study,
      we combine techniques for specifying high-order epistasis among risk SNPs with an
      existing program GWAsimulator [Li and Li, 2008] to achieve rapid whole-genome
      simulation with accurate modeling of complex interactions. We considered various
      approaches to specifying interaction models including the following: departure
      from product of marginal effects for pairwise interactions, product terms in
      logistic regression models for low-order interactions, and penetrance tables
      conforming to marginal effect constraints for high-order interactions or
      prescribing known biological interactions. Methods for conversion among different
      model specifications are developed using penetrance table as the fundamental
      characterization of disease models. The new program, called simGWA, is capable of
      efficiently generating large samples of GWAS data with high precision. We show
      that data simulated by simGWA are faithful to template LD structures, and conform
      to prespecified diseases models with (or without) interactions. 

PMID- 24114850
TI  - Xenobiotic metabolism induction and bulky DNA adducts generated by particulate
      matter pollution in BEAS-2B cell line: geographical and seasonal influence.
AB  - Airborne particulate matter (PM) toxicity is of growing interest as diesel
      exhaust particles have been classified as carcinogenic to humans. However, PM is
      a mixture of chemicals, and respective contribution of organic and inorganic
      fractions to PM toxicity remains unclear. Thus, we analysed the link between
      chemical composition of PM samples and bulky DNA adduct formation supported by
      CYP1A1 and 1B1 genes induction and catalytic activities. We used six native PM
      samples, collected in industrial, rural or urban areas, either during the summer
      or winter, and carried out our experiments on the human bronchial epithelial cell
      line BEAS-2B. Cell exposure to PM resulted in CYP1A1 and CYP1B1 genes induction.
      This was followed by an increase in EROD activity, leading to bulky DNA adduct
      formation in exposed cells. Bulky DNA adduct intensity was associated to global
      EROD activity, but this activity was poorly correlated with CYPs mRNA levels.
      However, EROD activity was correlated with both metal and polycyclic aromatic
      hydrocarbon (PAH) content. Finally, principal components analysis revealed three
      clusters for PM chemicals, and suggested synergistic effects of metals and PAHs
      on bulky DNA adduct levels. This study showed the ability of PM samples from
      various origins to generate bulky DNA adducts in BEAS-2B cells. This formation
      was promoted by increased expression and activity of CYPs involved in PAHs
      activation into reactive metabolites. However, our data highlight that bulky DNA
      adduct formation is only partly explained by PM content in PAHs, and suggest that
      inorganic compounds, such as iron, may promote bulky DNA adduct formation by
      supporting CYP activity.

PMID- 24114851
TI  - Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its
      pathogenesis.
AB  - Essential tremor (ET) encompasses a group of progressive neurological diseases in
      which the primary clinical feature is kinetic tremor of the arms. There is
      accumulating evidence to suggest that the cerebellum is involved in the
      pathogenesis of ET; the clinical presentation, neurophysiological data, and
      functional and metabolic abnormalities revealed by neuroimaging studies all point
      toward the dysregulation of cerebellar circuits. Recent neuropathological
      findings at postmortem demonstrate that Purkinje neurons, and some brainstem
      neurons, play an integral role in the pathogenesis of this common neurological
      disorder. The assessment of Purkinje cell linear density shows that Purkinje
      density is abnormal in ET brains. Specific efforts need be devoted to
      understanding the molecular and cellular events occurring in the Purkinje neurons
      of the cerebellar cortex, which are emerging as being of particular importance in
      the pathogenesis of ET in a subgroup of patients.

PMID- 24114852
TI  - Amine-based polar solvent treatment for highly efficient inverted polymer solar
      cells.
AB  - The interfacial dipolar polarization in inverted structure polymer solar cells,
      which arises spontaneously from the absorption of ethanolamine end groups, such
      as amine and hydroxyl groups on ripple-structure zinc oxide (ZnO-R), lowers the
      contact barrier for electron transport and extraction and leads to enhanced
      electron mobility, suppression of bimolecular recombination, reduction of the
      contact resistance and series resistance, and remarkable enhancement of the power
      conversion efficiency. 

PMID- 24114853
TI  - An efficient gold-catalyzed domino process for the construction of tetracyclic
      ketoethers.

PMID- 24114854
TI  - Predictors for return to work for those with occupational respiratory disease:
      clinical and structural factors.
AB  - BACKGROUND: Few occupational researchers have examined "return to work" among
      patients with work-related respiratory diseases. In addition, prior studies have
      emphasized individual patient characteristics rather than a more multi
      dimensional approach that includes both clinical and structural factors. METHODS:
      A retrospective chart review identified patients with occupational respiratory
      diseases in the Occupational Health Clinical Center, Syracuse, NY between 1991
      and 2009. We assessed predictors of work status using an exploratory, sequential
      mixed methods research design, multinomial (n = 188) and Cox regressions (n =
      130). RESULTS: The findings suggest that patients with an increased number of
      diagnoses, non-union members, and those who took more than a year before clinical
      presentation had significantly poorer work status outcomes, after adjusting for
      age, education level, and relevant diagnoses. CONCLUSIONS: Efforts to prevent
      slow return to work after developing occupational respiratory disease should
      recognize the importance of timely access to occupational health services,
      disease severity, union membership, and smoking status.

PMID- 24114855
TI  - Combined HER2 analysis of biopsies and surgical specimens to optimize detection
      of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study.
AB  - BACKGROUND: HER2 is overexpressed in 10 to 20% of gastro-esophageal
      adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients.
      We conducted a study to compare HER2 expression between diagnostic biopsies (DBs)
      and surgical specimens (SSs) of GE-ADK, and to determine the influence of non
      trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression.
      PATIENTS AND METHODS: Pathological specimens from biopsies of 228 patients
      operated on between 2004 and 2011 were collected. Two cohorts treated (n = 141)
      or not (n = 87) with a NAC were constituted. Two blind independent pathological
      HER2 analyses on DB and on SS were carried out using immunohistochemistry (IHC)
      and colorimetric in situ hybridization (CISH). HER-2 overexpression (HER2+) was
      defined by a score 3+ in IHC, or 2+ with a positive CISH test, according to the
      specific HER2 scoring guidelines for GE-ADK. RESULTS: Paired HER2 status could be
      determined for 218 out of the 228 patients (95.6%). HER2+ rates were 13.3% on DB
      (29/218) and 14.7% on SS (32/218). HER2+ tumors were mainly cardial or esophageal
      adenocarcinomas, with a well-differentiated, intestinal histological type. HER2
      status differed between DB and SS in 6% of cases. When DB analyses were added to
      SS analyses, the relative increase in HER2+ cases was 13.5% (17.1% for patients
      with NAC and 23.5% for patients with histological response to NAC, versus 7.1%
      for patients without NAC, P = 0.4, NS). Differences between DB and SS HER2
      expression could be explained by intratumoral heterogeneity and by a HER2
      expression decrease in SS after NAC in responding patients possibly due to a
      higher chemosensitivity of HER2-positive clones. CONCLUSION: The determination of
      HER2 status on DB provides results that complete those obtained with SS.
      Combining the analysis of DB and of SS enables to optimize the selection of
      trastuzumab-eligible patients in case of metastatic relapse, and particularly in
      previously NAC-responding patients.

PMID- 24114856
TI  - Quantitative assessment of lymph vascular space invasion (LVSI) provides
      important prognostic information in node-negative breast cancer.
AB  - BACKGROUND: Some studies investigating the prognostic value of lymph vascular
      space invasion (LVSI) have shown an association between LVSI and disease-free
      survival. Definitive criteria and optimal determination of this parameter remain
      unclear, however, especially regarding the clinical relevance of LVSI
      quantification. PATIENTS AND METHODS: A subset of node-negative breast carcinomas
      from premenopausal patients from the European Organization for the Research and
      Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy
      patients with T1-T3, N0-2, and M0 breast cancer (BC) was selected and scored for
      LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells
      was determined in the largest tumor embolus within the lymph vessels. These two
      parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The
      optimal cutoff for this parameter was calculated in a test set (N = 120), tested
      in a validation set (N = 238), and compared with simple quantitation of the
      number of LVSI foci. RESULTS: Tumors with a single LVSI focus are not associated
      with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval
      (CI) 0.762-2.656]. The LVSI TB had higher sensitivity and specificity compared
      with simple determination of the number of LVSI foci. LVSI TB was independently
      associated with disease-free survival in the validation set (HR 2.366, 95% CI
      1.369-4.090, P = 0.002) in multivariate analysis and provided prognostic
      information in both the low- and high-risk node-negative BC groups (P < 0.001 and
      P = 0.007, respectively). CONCLUSION: The determination of the number of LVSI
      foci multiplied by the number of tumor cells gives the most reliable quantitative
      assessment of this parameter, which can provide prognostic information in node
      negative BC.

PMID- 24114857
TI  - Discordance in ERalpha, PR and HER2 receptor status across different distant
      breast cancer metastases within the same patient.
AB  - BACKGROUND: We studied discordance in estrogen receptor alpha (ERalpha),
      progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)
      status between multiple distant metastases from the same breast cancer patient.
      MATERIAL AND METHODS: Multiple distant metastases from 55 female patients were
      stained for ERalpha, PR and HER2 by immunohistochemistry and in situ
      hybridization for confirmation of the HER2 status. RESULTS: Different metastatic
      sites within the same patient showed discordance in ERalpha receptor status in
      7.3% or 10.9% of patients (using a 10% or 1% threshold for positivity,
      respectively). For PR, 29.1% or 30.9% of patients showed discordance. Taking
      ERalpha and PR together, 36.4% of cases (both thresholds) showed discrepancy
      between metastases. In 10.9% (10% threshold) or 14.5% of patients (1% threshold),
      such discordance could have clinical consequences with regard to hormonal
      treatment. For HER2, there was 3.6% discordance on the immunohistochemical level
      but 0% on the gene level. CONCLUSION: In a significant proportion of metastatic
      breast cancer patients, discordance in ERalpha and PR receptor status between
      different metastatic sites was observed. This implies that multiple metastases
      may need to be biopsied to optimally reassess receptors.

PMID- 24114858
TI  - DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising
      treatment for recurrent advanced squamous cell anal carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease,
      mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with
      mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in
      >20% of the patients. After treatment failure, cisplatin (CDDP)-based
      chemotherapy is the standard option, but complete response (CR) is a rare event
      and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients
      with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel
      75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days
      every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV)
      genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up
      of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1
      months). Four patients achieved a complete remission and remain relapse-free at
      the time of analysis with a progression-free survival of 19, 33, 43 and 88
      months. Three of these patients underwent surgery for all involved metastatic
      sites. For all of them, pathological CR was confirmed. DCF regimen appeared
      feasible in these patients previously exposed to pelvic CRT, and no grade IV
      toxicity occurred. All patients in complete remission had HPV-16-positive SCCA,
      while HPV could only be detected among 50% of the non-responding patients. Of
      interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these
      patients, while none of non-responders expressed p16. CONCLUSION: The high level
      of complete and long-lasting remission among SCCA patients treated with DCF
      regimen supports the assessment of this strategy in prospective cohorts.

PMID- 24114859
TI  - Association of somatic DNA methylation variability with progression-free survival
      and toxicity in ovarian cancer patients.
AB  - BACKGROUND: We have addressed whether inter-individual methylation variation in
      somatic (white blood cells, WBCs) DNA of ovarian cancer patients provides
      potential for prognostic and/or pharmacoepigenetic stratification. PATIENTS AND
      METHODS: WBC DNA methylation was analysed by bisulphite pyrosequencing at ataxia
      telangiectasia mutated (ATM), estrogen receptor 1 (ESR1), progesterone receptor
      (PGR), mutL homologue 1 (MLH1), breast cancer susceptibility gene (BRCA1),
      secreted frizzled-related protein 1 (SFRP1), stratifin (SFN), retinoic acid
      receptor beta (RARB) loci and the repetitive element LINE1 in 880 SCOTROC1 trial
      patients [paclitaxel (Taxol)-carboplatin versus docetaxel (Taxotere)-carboplatin
      as primary chemotherapy for stage Ic-IV epithelial ovarian cancer]. RESULTS: We
      observed no significant associations (P < 0.005, after correction for multiple
      testing) for progression-free survival (PFS) using test and validation sets.
      However, we did identify mean SFN methylation associated with PFS (hazard ratio,
      HR = 1.01 per 1% increase in methylation, q = 0.028); particularly in the
      paclitaxel (HR = 1.01, q = 0.006), but not in the docetaxel arm in stratified
      analyses. Furthermore, higher methylation within the ESR1 gene was associated
      with CA125 response (odds ratio, OR = 1.06, q = 0.04) and with neuropathy (HR =
      0.95, q = 0.002), but only in the paclitaxel arm of the trial. CONCLUSIONS: This
      is the first study linking DNA methylation variability in WBC to clinical
      outcomes for any tumour type; the data generated on novel prognostic and
      pharmacoepigenetic DNA methylation biomarkers in the circulation now need
      independent further evaluation.

PMID- 24114860
TI  - Patterns of multiple victimization among maltreated children in Navy families.
AB  - The current study examined the cumulative risk associated with children's
      exposure to multiple types of parent-inflicted victimization. The sample was
      comprised of 195 children who were 7 to 17 years old (64.1% female and 48.2% non
      White) at the time of referral to the United States Navy's Family Advocacy
      Program due to allegations of sexual abuse, physical abuse, or parental intimate
      partner violence. We conducted an exploratory latent class analysis to identify
      distinct subgroups of children based on lifetime victimization. We hypothesized
      that at least 2 classes or subgroups would be identified, with 1 characterized by
      greater victimization and poorer outcomes. Results indicated that 3 classes of
      children best fit the data: (a) high victimization across all 3 categories, (b)
      high rates of physical abuse and witnessing intimate partner violence, and (c)
      high rates of physical abuse only. Findings indicated that the high victimization
      class was at greatest risk for alcohol and substance use, delinquent behavior,
      and meeting criteria for posttraumatic stress disorder (PTSD) and/or depression 1
      year later (odds ratio = 4.53). These findings highlight the serious mental
      health needs of a small but significantly high-risk portion of multiply
      victimized children entering the child welfare system. 

PMID- 24114861
TI  - Traditional multiplicity adjustment methods in clinical trials.
AB  - This tutorial discusses important statistical problems arising in clinical trials
      with multiple clinical objectives based on different clinical variables,
      evaluation of several doses or regiments of a new treatment, analysis of multiple
      patient subgroups, etc. Simultaneous assessment of several objectives in a single
      trial gives rise to multiplicity. If unaddressed, problems of multiplicity can
      undermine integrity of statistical inferences. The tutorial reviews key concepts
      in multiple hypothesis testing and introduces main classes of methods for
      addressing multiplicity in a clinical trial setting. General guidelines for the
      development of relevant and efficient multiple testing procedures are presented
      on the basis of application-specific clinical and statistical information. Case
      studies with common multiplicity problems are used to motivate and illustrate the
      statistical methods presented in the tutorial, and software implementation of the
      multiplicity adjustment methods is discussed.

PMID- 24114862
TI  - Internet-based contingency management to promote smoking cessation: a randomized
      controlled study.
AB  - We evaluated an Internet-based contingency management intervention to promote
      smoking cessation. Participants in the contingent group (n = 39) earned vouchers
      contingent on video confirmation of breath carbon monoxide (CO) <= 4 parts per
      million (ppm). Earnings for participants in the noncontingent group (n = 38) were
      independent of CO levels. Goals and feedback about smoking status were provided
      on participants' homepages. The median percentages of negative samples during the
      intervention in the noncontingent and contingent groups were 25% and 66.7%,
      respectively. There were no significant differences in absolute CO levels or
      abstinence at 3- and 6-month follow-ups. Compared to baseline, however,
      participants in both groups reduced CO by an estimated 15.6 ppm during the
      intervention phases. The results suggest that the contingency for negative COs
      promoted higher rates of abstinence during treatment, and that other elements of
      the system, such as feedback, frequent monitoring, and goals, reduced smoking. 

PMID- 24114863
TI  - Projected costs and consequences of computed tomography-determined fractional
      flow reserve.
AB  - BACKGROUND: Randomized trials have shown that fractional flow reserve (FFR)
      guided percutaneous coronary intervention (PCI) improves clinical outcome and
      reduces costs compared with visually guided PCI. FFR has been measured during
      invasive coronary angiography (ICA), but can now be derived noninvasively from
      coronary computed tomography (CT) angiography (cCTA) images (FFRCT ). The
      potential value of FFRCT in clinical decision making is unknown. HYPOTHESIS: Use
      of FFRCT can reduce costs and improve outcomes among patients with suspected
      coronary artery disease. METHODS: We used clinical data from 96 patients in the
      DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive
      Fractional Flow Reserve) study and outcomes data from the literature to project
      the initial management costs and 1-year death/myocardial infarction rates
      associated with 5 clinical strategies: (1) ICA with PCI based on visual
      angiographic assessment, (2) ICA with FFRICA -guided PCI, (3) cCTA followed by
      ICA and PCI based on visual assessment, (4) cCTA followed by ICA with FFRICA 
      guided PCI, and (5) cCTA FFRCT and PCI of lesions with FFRCT <=0.80. RESULTS: The
      projected initial management costs were highest for the ICA/visual strategy ($10
      702), and lowest for the cCTA/FFRCT /ICA strategy ($7674). The use of FFRCT to
      select patients for ICA and PCI would result in 30% lower costs and 12% fewer
      events at 1 year compared with the most commonly used ICA/visual strategy.
      CONCLUSIONS: A strategy of using FFRCT to guide the selection of patients for ICA
      and PCI might reduce costs and improve clinical outcomes in patients with
      suspected coronary artery disease.

PMID- 24114864
TI  - beta-Amyloid is transmitted via neuronal connections along axonal membranes.
AB  - OBJECTIVE: beta-amyloid plaque is a critical pathological feature of Alzheimer
      disease. Pathologic studies suggest that neurodegeneration may occur in a
      retrograde fashion from axon terminals near beta-amyloid plaques, and that plaque
      may spread through brain regions. However, there is no direct experimental
      evidence to show transmission of beta-amyloid. METHODS: Microscopic imaging data
      of beta-amyloid transmission was acquired in cortical neuron cultures from
      Sprague-Dawley rat embryos using polydimethylsiloxane (PDMS) microfluidic culture
      chambers and in brain sections from in vivo beta-amyloid injection. RESULTS: We
      present direct imaging evidence in cultured cortical neurons, using PDMS
      microfluidic culture chambers, that beta-amyloid is readily absorbed by axonal
      processes and retrogradely transported to neuronal cell bodies. Transmission of
      beta-amyloid via neuronal connections was also confirmed in mouse brain. beta
      Amyloid absorbed by distal axons accumulates in axonal swellings, mitochondria,
      and lysosomes of the cell bodies. Interestingly, dynasore, an inhibitor of
      dynamin, which is a protein indispensable for endocytosis, did not prevent
      retrograde transport of beta-amyloid, indicating that beta-amyloid is absorbed
      onto axonal membranes and transmitted via them to the cell body. Dynasore did
      decrease the transneuronal transmission of beta-amyloid, suggesting that this
      requires the internalization and secretion of beta-amyloid. INTERPRETATION: Our
      findings provide direct in vitro and in vivo evidence for spreading of beta
      amyloid through neuronal connections, and suggest possible therapeutic approaches
      to blocking this spread.

PMID- 24114865
TI  - Soluble concentrations of the interleukin receptor family member ST2 and beta
      blocker therapy in chronic heart failure.
AB  - BACKGROUND: Concentrations of soluble (s)ST2 predict prognosis in heart failure.
      We recently found changing doses of beta-blocker (BB) may affect sST2
      concentrations. It remains unclear whether sST2 concentrations identify benefit
      of BB therapy, however. METHODS AND RESULTS: A total of 151 subjects with heart
      failure attributable to left ventricular systolic dysfunction were examined in
      this post hoc analysis; >96% were taking BB at enrollment. Medication regimen and
      sST2 values were obtained during 10 months. Cardiovascular events were examined
      as a function of baseline sST2 status (low <=35 versus high >35 ng/mL) and final
      achieved BB dose (high >=50 versus low <50 mg daily equivalent dose of metoprolol
      succinate). Patients with low sST2 titrated to high-dose BB had the lowest
      cardiovascular event rate at 0.53 events (P=0.001), and lowest cumulative hazard
      (P=0.003). Those with low sST2/low-dose BB, or high sST2/high-dose BB had
      intermediate outcomes (0.92 and 1.19 events). Patients with high sST2 treated
      with low-dose BB had the highest cardiovascular event rate (2.08 events) and the
      highest cumulative hazard. Compared with low sST2/high-dose BB, those with high
      sST2 treated with low-dose BB had an odds ratio of 6.77 (P<0.001) for a
      cardiovascular event. Patients with low sST2/low-dose BB or high sST2/high-dose
      BB had intermediate odds ratios for cardiovascular events (P=0.18 and 0.02).
      Similar results were found for heart failure hospitalization and cardiovascular
      death. CONCLUSIONS: Although BB therapy exerted dose-related benefits across all
      study participants, sST2 measurement identifies patients with chronic heart
      failure who may particularly benefit from higher BB doses. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00351390.

PMID- 24114866
TI  - Round window closure affects cochlear responses to suprathreshold stimuli.
AB  - OBJECTIVES/HYPOTHESIS: The round window acts as a vent for releasing inner ear
      pressure and facilitating basilar membrane vibration. Loss of this venting
      function affects cochlear function, which leads to hearing impairment. In an
      effort to identify functional changes that might be used in clinical diagnosis of
      round window atresia, the current investigation was designed to examine how the
      cochlea responds to suprathreshold stimuli following round window closure. STUDY
      DESIGN: Prospective, controlled, animal study. METHODS: A rat model of round
      window occlusion (RWO) was established. With this model, the thresholds of
      auditory brainstem responses (ABR) and the input/output (IO) functions of
      distortion product otoacoustic emissions (DPOAEs) and acoustic startle responses
      were examined. RESULTS: Round window closure caused a mild shift in the
      thresholds of the auditory brainstem response (13.5 +/- 9.1 dB). It also reduced
      the amplitudes of the distortion product otoacoustic emissions and the slope of
      the input/output functions. This peripheral change was accompanied by a
      significant reduction in the amplitude, but not the threshold, of the acoustic
      startle reflex, a motor response to suprathreshold sounds. CONCLUSIONS: In
      addition to causing mild increase in the threshold of the auditory brainstem
      response, round window occlusion reduced the slopes of both distortion product
      otoacoustic emissions and startle reflex input/output functions. These changes
      differ from those observed for typical conductive or sensory hearing loss, and
      could be present in patients with round window atresia. However, future clinical
      observations in patients are needed to confirm these findings.

PMID- 24114867
TI  - Permutation tests for analyzing cospeciation in multiple phylogenies:
      applications in tri-trophic ecology.
AB  - There is a need for a reliable statistical test which is appropriate for
      assessing cospeciation of more than two phylogenies. We have developed an
      algorithm using a permutation method that can be used to test for and infer tri
      trophic evolutionary relationships of organisms given both their phylogenies and
      pairwise interactions. An overall statistic has been developed based on the
      dominant eigenvalue of a covariance matrix, and compared to values of the
      statistic computed when tree labels are permuted. The resulting overall p-value
      is used to test for the presence or absence of cospeciation in a tri-trophic
      system. If cospeciation is detected, we propose new test statistics based on
      partial correlations to uncover more details about the relationships between
      multiple phylogenies. One of the strengths of our method is that it allows more
      parasites than hosts or more hosts than parasites, with multiple associations and
      more than one parasite attached to a host (or one parasite attached to multiple
      hosts). The new method does not require any parametric assumptions of the
      distribution of the data, and unlike the old methods, which utilize several
      pairwise steps, the overall statistic used is obtained in one step. We have
      applied our method to two published datasets where we obtained detailed
      information about the strength of associations among species with calculated
      partial p-values and one overall p-value from the dominant eigenvalue test
      statistic. Our permutation method produces reliable results with a clear
      procedure and statistics applied in an intuitive manner. Our algorithm is useful
      in testing evidence for three-way cospeciation in multiple phylogenies with tri
      trophic associations and determining which phylogenies are involved in
      cospeciation.

PMID- 24114868
TI  - In vitro and in vivo evaluation of a once-weekly formulation of an antidiabetic
      peptide drug exenatide in an injectable thermogel.
AB  - An injectable thermogel composed of poly(lactic acid-co-glycolic acid)
      poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock
      copolymers was evaluated as the matrix of a long-acting drug delivery system of
      exenatide (EXT), an antidiabetic peptide. The optimal gel formulation containing
      2 mg/mL EXT and three pharmaceutical excipients (1.25 wt % zinc acetate, 5 wt %
      PEG200, and 5 wt % sucrose) was injected subcutaneously, and its pharmacokinetics
      was investigated. Both in vitro and in vivo release profiles exhibited a
      sustained release of EXT over 1 week. After a subcutaneous injection of the EXT
      formulation into db/db mice, the blood glucose level was maintained in a normal
      range up to 7 days and meanwhile the growth of body weight was suppressed. The in
      vivo results were consistent with the in vitro EXT-release profile. Moreover,
      twice injections of the gel formulation resulted in the higher blood insulin
      level and lower plasma concentration of glycosylated hemoglobin compared with
      twice-daily injections of an EXT solution for 18 days. Histological observations
      manifested the protection of islet due to administration of the gel formulation.
      Therefore, the PLGA-PEG-PLGA thermogel provided an excellent candidate for a once
      weekly delivery system of EXT, and the optimal EXT formulation not only afforded
      therapeutic efficacy but also improved patient compliance.

PMID- 24114869
TI  - The meaning of urinary hesitancy in women with overactive bladder Re: Park KK,
      Lee SH, Kim YJ, Choi YD, Mah SY: "Association between urinary hesitancy symptoms
      and uroflowmetry measured urinary hesitancy time in men with lower urinary tract
      symptoms. Neurourol Urodyn. 2011 May 01: 30:578-82".

PMID- 24114870
TI  - Cochlear implant fixation using a subperiosteal tight pocket without either
      suture or bone-recess technique.
AB  - OBJECTIVES/HYPOTHESIS: To assess the complication and migration rates associated
      with the fixation of cochlear implant receiver-stimulators using a subperiosteal
      tight pocket without either suture fixation or bone recession. STUDY DESIGN: Dual
      institution retrospective case review. METHODS: A retrospective case review was
      conducted at two tertiary referral centers. All patients who underwent cochlear
      implantation with device fixation using a subperiosteal tight pocket without
      suturing over the device or recessing of the receiver stimulator in bone were
      identified. There was a minimum follow-up period of 6 months. Outcome measures
      included intraoperative and postoperative complications, including evidence of
      device migration associated with interference with external device use or the
      need for revision surgery. Other outcome measures included soft tissue flap
      complications. RESULTS: Sixty-two patients were identified with a mean age of 39
      years, (range 1.5-5 years). The average follow-up period was 32.6 months (range 6
      120 months). Device manufacturers included Cochlear Corporation (Denver, CO)
      (n=44), MED-EL (Durham, NC) (n=12), and Advanced Bionics (Valencia, CA) (n=6).
      There were no associated intraoperative complications related to subperiosteal
      pocket fixation of the receiver stimulator, and no cases of migration were
      identified. CONCLUSION: Fixation of the cochlear implant receiver stimulator
      using a subperiosteal tight pocket without either suture fixation or bone
      recession has been demonstrated to be feasible across a range of patient
      demographics and cochlear implant devices. This method of fixation appears to
      allow for an efficient and minimally invasive approach without compromising
      patient safety or device performance. LEVEL OF EVIDENCE: 4.

PMID- 24114871
TI  - Improved staining of phosphoproteins with high sensitivity in polyacrylamide gels
      using Stains-All.
AB  - An improved Stains-All (ISA) staining method for phosphoproteins in SDS-PAGE was
      described. Down to 0.5-1 ng phosphoproteins (alpha-casein, beta-casein, or
      phosvitin) can be successfully selectively detected by ISA stain, which is
      approximately 120-fold higher than that of original Stains-All stain, but is
      similar to that of commonly used Pro-Q Diamond stain. Furthermore, unlike the
      original Stains-All protocol that was time consuming and light unstable, ISA
      stain could be completed within 60 min without resorting to protect the gels from
      light during the whole staining procedure. According to the results, it is
      concluded that ISA stain is a rapid, sensitive, specific, and economic staining
      method for a broad application to the research of phosphoproteins. 

PMID- 24114872
TI  - Pyridine-enhanced head-to-tail dimerization of terminal alkynes by a rhodium-N
      heterocyclic-carbene catalyst.
AB  - A general regioselective rhodium-catalyzed head-to-tail dimerization of terminal
      alkynes is presented. The presence of a pyridine ligand (py) in a Rh-N
      heterocyclic-carbene (NHC) catalytic system not only dramatically switches the
      chemoselectivity from alkyne cyclotrimerization to dimerization but also enhances
      the catalytic activity. Several intermediates have been detected in the catalytic
      process, including the pi-alkyne-coordinated Rh(I) species [RhCl(NHC)(eta(2)
      HC=CCH2Ph)(py)] (3) and [RhCl(NHC){eta(2)-C(tBu)=C(E)CH=CHtBu}(py)] (4) and the
      Rh(III)-hydride-alkynyl species [RhClH{-C=CSi(Me)3}(IPr)(py)2] (5). Computational
      DFT studies reveal an operational mechanism consisting of sequential alkyne C-H
      oxidative addition, alkyne insertion, and reductive elimination. A 2,1
      hydrometalation of the alkyne is the more favorable pathway in accordance with a
      head-to-tail selectivity.

PMID- 24114873
TI  - The use of nuclear bone scanning after fibula free tissue transfer.
AB  - OBJECTIVES/HYPOTHESIS: To understand the role of nuclear bone scanning in the
      evaluation of threatened osteocutaneous free tissue transfers, identify patients
      who may benefit from nuclear bone scanning after head and neck reconstructive
      surgery, and be able to use nuclear bone scanning to help guide management of the
      threatened free flap. STUDY DESIGN: Retrospective case series design set in a
      tertiary referral center. METHODS: Records of patients undergoing bone scan in
      the context of threatened osteocutaneous free tissue transfer between July 1998
      and December 2008 were reviewed. RESULTS: Over a 10-year period, 205 fibula free
      tissue transfers were performed, with an overall 94% success rate. Fifteen
      fibular free flaps in 14 patients were determined to be threatened in the late
      postoperative period, and nuclear bone scanning was performed. Seven of 15 flaps
      had regions of certain flap nonviability, with five flaps clearly appearing
      viable on bone scanning. No graft read as potentially viable eventually failed.
      All grafts read as nonviable underwent exploration and debridement, with
      confirmation of nonviability in all cases. In eight cases, bone scanning allowed
      preoperative planning for soft tissue flap reconstruction. CONCLUSIONS: In those
      instances in which the skin paddle dies in the late postoperative period and
      determination of bone viability is required, a bone scan can demonstrate whether
      or not the bone is alive. This information can help determine the future
      operative and reconstructive options available for the patient.

PMID- 24114874
TI  - Drinking coffee burns hepatic fat by inducing lipophagy coupled with
      mitochondrial beta-oxidation.

PMID- 24114875
TI  - Physical (in)activity-dependent structural plasticity in bulbospinal
      catecholaminergic neurons of rat rostral ventrolateral medulla.
AB  - Increased activity of the sympathetic nervous system is thought to play a role in
      the development and progression of cardiovascular disease. Recent work has shown
      that physical inactivity versus activity alters neuronal structure in brain
      regions associated with cardiovascular regulation. Our physiological studies
      suggest that neurons in the rostral ventrolateral medulla (RVLM) are more
      responsive to excitation in sedentary versus physically active animals. We
      hypothesized that enhanced functional responses in the RVLM may be due, in part,
      to changes in the structure of RVLM neurons that control sympathetic activity. We
      used retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) to
      identify bulbospinal catecholaminergic (C1) neurons in sedentary and active rats
      after chronic voluntary wheel-running exercise. We then digitally reconstructed
      their cell bodies and dendrites at different rostrocaudal levels. The dendritic
      arbors of spinally projecting TH neurons from sedentary rats were more branched
      than those of physically active rats (P < 0.05). In sedentary rats, dendritic
      branching was greater in more rostral versus more caudal bulbospinal C1 neurons,
      whereas, in physically active rats, dendritic branching was consistent throughout
      the RVLM. In contrast, cell body size and the number of primary dendrites did not
      differ between active and inactive animals. We suggest that these structural
      changes provide an anatomical underpinning for the functional differences
      observed in our in vivo studies. These inactivity-related structural and
      functional changes may enhance the overall sensitivity of RVLM neurons to
      excitatory stimuli and contribute to an increased risk of cardiovascular disease
      in sedentary individuals.

PMID- 24114876
TI  - Glycerophosphocholine utilization by Candida albicans: role of the Git3
      transporter in virulence.
AB  - Candida albicans contains four ORFs (GIT1,2,3,4) predicted to encode proteins
      involved in the transport of glycerophosphodiester metabolites. Previously, we
      reported that Git1, encoded by ORF 19.34, is responsible for the transport of
      intact glycerophosphoinositol but not glycerophosphocholine (GroPCho). Here, we
      report that a strain lacking both GIT3 (ORF 19.1979) and GIT4 (ORF 19.1980) is
      unable to transport [(3)H]GroPCho into the cell. In the absence of a GroPCho
      transporter, C. albicans can utilize GroPCho via a mechanism involving
      extracellular hydrolysis. Upon reintegration of either GIT3 or GIT4 into the
      genome, measurable uptake of [(3)H]GroPCho is observed. Transport assays and
      kinetic analyses indicate that Git3 has the greater transport velocity. We
      present evidence that GDE1 (ORF 19.3936) codes for an enzyme with
      glycerophosphodiesterase activity against GroPCho. Homozygous deletion of GDE1
      results in a buildup of internal GroPCho that is restored to wild type levels by
      reintegration of GDE1 into the genome. The transcriptional regulator, Pho4, is
      shown to regulate the expression of GIT3, GIT4, and GDE1. Finally, Git3 is shown
      to be required for full virulence in a mouse model of disseminated candidiasis,
      and Git3 sequence orthologs are present in other pathogenic Candida species. In
      summary, we have characterized multiple aspects of GroPCho utilization by C.
      albicans and have demonstrated that GroPCho transport plays a key role in the
      growth of the organism in the host. 

PMID- 24114877
TI  - Immunopathogenesis of dengue hemorrhagic fever: contribution to the study of
      human liver lesions.
AB  - Dengue infection is an important tropical disease worldwide. The host immune
      response has been studied in order to better understand lesion mechanisms. It was
      performed an immunohistochemical study in 14 specimens of liver from patients
      with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors
      present in liver lesions and their possible role in the pathogenesis of hepatic
      injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3,
      IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta.
      Cells expressing IL12, IL13, JAk1, STAT1, and NF-kappaB were rarely visualized.
      Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular
      activation and cytokine production. Cytotoxic response seems to play a role.
      Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can
      significantly suppresses their generation. The expression of Treg cells is
      diminished probably as a result of the high frequency of these cytokines. Both
      cytokines play a role in the increased vascular permeability and edema observed
      in dengue liver specimens, with consequent plasma leakage and severity of the
      disease. It was observed a regular expression of IL-18 in hepatocytes and
      lymphocytes of the inflammatory infiltrate in portal tract, which reflects the
      acute inflammatory response that occurs in the liver and contributes to hepatic
      injury. At least in part, the increased number of cells expressing IL-18 could
      play a role of "up" regulation of FasL and correlate to the phenomenon of
      apoptosis, a mechanism of destruction of hepatocytes in DHF.

PMID- 24114878
TI  - Identification of metabolomic biomarkers for drug-induced acute kidney injury in
      rats.
AB  - Nephrotoxicity is a common side effect observed during both nonclinical and
      clinical drug development investigations. The present study aimed to identify
      metabolomic biomarkers that could provide early and sensitive indication of
      nephrotoxicity in rats. Metabolomic analyses were performed using capillary
      electrophoresis-time-of-flight mass spectrometry on rat plasma collected at 9 and
      24 h after a single dose of 2-bromoethylamine or n-phenylanthranilic acid and at
      24 h after 7 days of repeated doses of gentamicin, cyclosporine A or cisplatin.
      Among a total of 169 metabolites identified, 3-methylhistidine (3-MH), 3-indoxyl
      sulfate (3-IS) and guanidoacetate (GAA) were selected as candidate biomarkers.
      The biological significance and reproducibility of the observed changes were
      monitored over time in acute nephrotoxicity model rats treated with a single dose
      of cisplatin, with the glomerular filtration rate monitored by determination of
      creatinine clearance. Increased plasma levels of 3-MH and 3-IS were related to a
      decline in glomerular filtration due to a renal failure. In contrast, the
      decrease in plasma GAA, which is synthesized from arginine and glycine in the
      kidneys, was considered to reflect decreased production due to renal malfunction.
      Although definitive validation studies are required to confirm their usefulness
      and reliability, 3-MH, 3-IS and GAA may prove to be valuable plasma biomarkers
      for monitoring nephrotoxicity in rats.

PMID- 24114879
TI  - Copper-catalyzed trifluoromethylation-cyclization of enynes: highly
      regioselective construction of trifluoromethylated carbocycles and heterocycles.
AB  - Regioselective trifluoromethylation-cyclization: A method for copper-catalyzed
      trifluoromethylation-cyclization of simple enynes using the C?C triple bond as a
      nucleophile is reported for the first time. The reaction proceeds efficiently in
      a highly regioselective manner to give various 5- or 6-exo-dig carbocycles and
      heterocycles in moderate to high yields. 

PMID- 24114880
TI  - Are substantia nigra neurons subject to mitochondrial dysfunction in early life
      more able to adapt?

PMID- 24114881
TI  - GIAO/DFT studies on 1,2,4-triazole-5-thiones and their propargyl derivatives.
AB  - Density functional theory (DFT)/Becke-Lee-Yang-Parr (B3LYP) and gauge-including
      atomic orbital (GIAO) calculations were performed on a number of 1,2,4-triazole
      derivatives, and the optimized structural parameters were employed to ascertain
      the nature of their predominant tautomers. (13)C and (15)N NMR chemical shifts of
      3-substituted 1,2,4-triazole-5-thiones and their propargylated derivatives were
      calculated via GIAO/DFT approach at the B3LYP level of theory with geometry
      optimization using a 6-311++G** basis set. A good agreement between theoretical
      and experimental (13)C and (15)N NMR chemical shifts could be found for the
      systems investigated. The data generated were useful in predicting (15)N chemical
      shifts of all the nitrogen atoms of the triazole ring, some of which could not be
      obtained in solution state (15)N HMBC/HSQC NMR measurements. The energy profile
      computed for the dipropargylated derivatives was found to follow the product
      distribution profile of regioisomers formed during propargylation of 1,2,4
      triazole thiones.

PMID- 24114882
TI  - Stable dropwise condensation for enhancing heat transfer via the initiated
      chemical vapor deposition (iCVD) of grafted polymer films.
AB  - Ultra-thin copolymer films are deposited by initiated chemical deposition (iCVD)
      to investigate their performance under the condensation of water vapor. By
      forming a grafted interface between the coating and the substrate, the films
      exhibit stable dropwise condensation even when subjected to 100  degrees C steam.
      The applicability of the iCVD to complex substrate geometries is demonstrated on
      a copper condenser coil. 

PMID- 24114883
TI  - Longitudinal assessment of amniotic fluid volume in monoamniotic twin gestations.
AB  - OBJECTIVE: The aim of this study is to describe normal amniotic fluid volume
      through gestation in a cohort of normal monoamniotic (MA) twins. METHOD: Our
      ultrasound database was queried for MA twin gestations from 2004 to 2011.
      Monochorionic twin pregnancies mimicking MA gestations, such as twin-twin
      transfusion syndrome, were excluded. Complicated MA gestations and higher-order
      multifetal gestations involving an MA pair were excluded. Thirty subjects were
      followed with serial amniotic fluid index (AFI) measurements from 15 to 32 weeks
      gestation. Using each AFI measurement as a unique data point, a quadratic
      regression model and a multi-level growth model were developed against
      gestational age (GA), providing a predicted AFI at each completed week, with a
      95% confidence interval. RESULTS: The quadratic regression least squares and
      multi-level growth models yielded the same curve comparing the AFI to the GA.
      Figure 1 depicts the model with the 95% confidence interval for normal amniotic
      fluid volume by GA for normal MA twins. Table 2 shows the 5th, 50th, and 95th
      percentiles for AFI by week from 15 to 32 weeks. CONCLUSION: We have generated
      normative data for amniotic fluid volume across gestation in uncomplicated MA
      twins. This can be used as a reference when managing MA pregnancies.

PMID- 24114884
TI  - Variance reduction in randomised trials by inverse probability weighting using
      the propensity score.
AB  - In individually randomised controlled trials, adjustment for baseline
      characteristics is often undertaken to increase precision of the treatment effect
      estimate. This is usually performed using covariate adjustment in outcome
      regression models. An alternative method of adjustment is to use inverse
      probability-of-treatment weighting (IPTW), on the basis of estimated propensity
      scores. We calculate the large-sample marginal variance of IPTW estimators of the
      mean difference for continuous outcomes, and risk difference, risk ratio or odds
      ratio for binary outcomes. We show that IPTW adjustment always increases the
      precision of the treatment effect estimate. For continuous outcomes, we
      demonstrate that the IPTW estimator has the same large-sample marginal variance
      as the standard analysis of covariance estimator. However, ignoring the
      estimation of the propensity score in the calculation of the variance leads to
      the erroneous conclusion that the IPTW treatment effect estimator has the same
      variance as an unadjusted estimator; thus, it is important to use a variance
      estimator that correctly takes into account the estimation of the propensity
      score. The IPTW approach has particular advantages when estimating risk
      differences or risk ratios. In this case, non-convergence of covariate-adjusted
      outcome regression models frequently occurs. Such problems can be circumvented by
      using the IPTW adjustment approach.

PMID- 24114885
TI  - Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis.
AB  - OBJECTIVE: To evaluate the association between the damage to the anterior and
      posterior visual pathway as evidence of the presence of retrograde and
      anterograde trans-synaptic degeneration in multiple sclerosis (MS). METHODS: We
      performed a longitudinal evaluation on a cohort of 100 patients with MS,
      acquiring retinal optical coherence tomography to measure anterior visual pathway
      damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular
      volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual
      pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within
      optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was
      used for MRI analysis. We evaluated the relationships between the damage in the
      anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple
      linear regressions, and general linear models. RESULTS: VBM analysis showed that
      RNFL thinning was specifically associated with atrophy of the visual cortex and
      with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex
      volume (beta = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl
      aspartate in visual cortex (beta = +1.075, 95% CI = +0.190 to +1.961), and lesion
      volume within optic radiations (beta = -2.551, 95% CI = -3.910 to -1.192)
      significantly influenced average RNFL thinning at study inclusion independently
      of other confounders, especially optic neuritis (ON). The model indicates that a
      decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6MUm in RNFL
      thickness. This association was also observed after 1 year of follow-up. Patients
      with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and
      mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower
      adjusted mean visual cortex volume than patients without ON. INTERPRETATION: Our
      results suggest the presence of trans-synaptic degeneration as a contributor to
      chronic axon damage in MS.

PMID- 24114886
TI  - Effect of intratonsillar injection of steroids on the palatine tonsils of
      rabbits.
AB  - OBJECTIVES/HYPOTHESIS: Nasal steroids may significantly improve nasal obstructive
      symptoms with a reduction of adenoid size in children, but they do not
      consistently yield the same concurrent effect on enlarged palatine tonsils.
      Failure of nasal steroids to decrease the size of palatine tonsils is believed to
      be attributable to location and washout by saliva. The purpose of this study was
      to determine if direct application of steroid via intratonsillar injection would
      reduce the size of palatine tonsils in the rabbit model. STUDY DESIGN:
      Prospective animal study. METHODS: Eight rabbits (16 tonsils) were administered
      intratonsillar injections of fluticasone (n = 8, 1 mg/ml) or saline (n = 8, 0.1
      ml) on days 0, 3, 7, 10, 14, and 17. Two rabbits (4 tonsils) received a single
      steroid injection to compare single versus multiple steroid injections. The
      rabbit's tonsil size was measured before each injection. After the fifty
      injections, the tonsils were harvested for histologic analysis. RESULTS: A total
      of 16 tonsils were analyzed. After five steroid injections, the reduction (-7.7
      mm(2)  +/- 4.27) in size was statistically significant when compared to reduction
      (6.12 mm(2)  +/- 6.57) in the saline injected group (P = 0.001). Repeated steroid
      injection was more potent than a single injection (-3.00 mm(2)  +/- 3.08) in
      reducing the size (P = 0.006). In histologic analysis, tonsils after repeated
      steroid injections were significantly smaller than saline-injected tonsils (P =
      0.014), without obvious lymphoid follicles. CONCLUSION: Repeated focal tonsillar
      injections of corticosteroids significantly reduced the size of palatine tonsils
      as compared to saline-injected controls. A single injection of corticosteroids
      appears to be effective, but not as effective, as multiple injections. LEVEL OF
      EVIDENCE: N/A.

PMID- 24114887
TI  - A critical review of the evidence base of imagery rehearsal for posttraumatic
      nightmares: pointing the way for future research.
AB  - In this article, the authors provide information on key characteristics of
      imagery rehearsal treatment protocols and examine the quality of reporting of
      randomized controlled and uncontrolled trials of imagery rehearsal for treating
      posttraumatic nightmares. Using a reliable and valid scale, two independent
      psychologists rated 16 trials. Most reports provided insufficient information on
      a range of variables including the definition of treatment delivery (e.g.,
      therapist supervision, treatment fidelity), description of the participant
      sample, data analysis (e.g., determination of sample size), and treatment
      assignment (e.g., randomization procedures). Low methodological quality and poor
      reporting can lead to inflation of estimates of treatment effects and
      inadequately substantiated conclusions, such as inflated effect sizes in meta
      analytic studies. Numerous imagery rehearsal protocols exist, but in some cases
      are given different names and tested in pilot studies, slowing progression in the
      field. Randomized controlled trials of imagery rehearsal with credible comparison
      conditions, examination of predictors of dropout and outcome, as well as
      dismantling studies of imagery rehearsal treatment components are needed. 

PMID- 24114888
TI  - Revision cochlear implantation following internal auditory canal insertion.
AB  - OBJECTIVES/HYPOTHESIS: In pediatric patients with congenital malformations of the
      inner ear, anomalies within the anatomy may facilitate unintentional insertion of
      the cochlear implant electrode into the internal auditory canal. Revision
      procedures for removal and replacement of cochlear implant electrodes following
      internal auditory canal insertion are fraught with potential danger, including
      the theoretical risk of injury to vasculature within the internal auditory canal,
      repeat insertion within the internal auditory canal, and cerebrospinal fluid
      leak. The objective of this presentation is to describe a technique for revision
      cochlear implantation following internal auditory canal insertion to minimize the
      potential associated risks. STUDY DESIGN: Case series. METHODS: A retrospective
      chart review was performed on all patients at a tertiary care facility who
      underwent revision cochlear implantation for internal auditory canal insertion
      between January 1999 and July 2011. RESULTS: A total of four patients referred
      from outside institutions have undergone revision cochlear implantation for
      internal auditory canal insertion. The records from these patients were reviewed.
      Electrodes were safely removed in all cases without injury to the anterior
      inferior cerebellar artery or its branches (i.e., labyrinthine artery). Complete
      insertion was accomplished on reimplantation. Neural response telemetry was
      performed in all cases, and responses were noted. Fluoroscopy was utilized to
      visualize electrode progression during insertion. A detailed description of the
      operative technique is provided. CONCLUSIONS: This case series describes a
      technique for revision cochlear implantation that appears to be safe and
      effective in preventing potential associated complications.

PMID- 24114889
TI  - Artificial intelligence techniques used in respiratory sound analysis--a
      systematic review.
AB  - Artificial intelligence (AI) has recently been established as an alternative
      method to many conventional methods. The implementation of AI techniques for
      respiratory sound analysis can assist medical professionals in the diagnosis of
      lung pathologies. This article highlights the importance of AI techniques in the
      implementation of computer-based respiratory sound analysis. Articles on computer
      based respiratory sound analysis using AI techniques were identified by searches
      conducted on various electronic resources, such as the IEEE, Springer, Elsevier,
      PubMed, and ACM digital library databases. Brief descriptions of the types of
      respiratory sounds and their respective characteristics are provided. We then
      analyzed each of the previous studies to determine the specific respiratory
      sounds/pathology analyzed, the number of subjects, the signal processing method
      used, the AI techniques used, and the performance of the AI technique used in the
      analysis of respiratory sounds. A detailed description of each of these studies
      is provided. In conclusion, this article provides recommendations for further
      advancements in respiratory sound analysis.

PMID- 24114890
TI  - In vivo validation of the electronic depth control probes.
AB  - In this article, we evaluated the electrophysiological performance of a novel,
      high-complexity silicon probe array. This brain-implantable probe implements a
      dynamically reconfigurable voltage-recording device, coordinating large numbers
      of electronically switchable recording sites, referred to as electronic depth
      control (EDC). Our results show the potential of the EDC devices to record good
      quality local field potentials, and single- and multiple-unit activities in
      cortical regions during pharmacologically induced cortical slow wave activity in
      an animal model.

PMID- 24114891
TI  - The suitability of EIT to estimate EELV in a clinical trial compared to oxygen
      wash-in/wash-out technique.
AB  - INTRODUCTION: Open endotracheal suctioning procedure (OSP) and recruitment
      manoeuvre (RM) are known to induce severe alterations of end-expiratory lung
      volume (EELV). We hypothesised that EIT lung volumes lack clinical validity. We
      studied the suitability of EIT to estimate EELV compared to oxygen wash-in/wash
      out technique. METHODS: Fifty-four postoperative cardiac surgery patients were
      enrolled and received standardized ventilation and OSP. Patients were randomized
      into two groups receiving either RM after suctioning (group RM) or no RM (group
      NRM). Measurements were conducted at the following time points: Baseline (T1),
      after suctioning (T2), after RM or NRM (T3), and 15 and 30 min after T3 (T4 and
      T5). We measured EELV using the oxygen wash-in/wash-out technique (EELVO2) and
      computed EELV from EIT (EELVEIT) by the following formula:
      EELVEITTx,y...=EELVO2+DeltaEELI*VT/DeltaZ. EELVEIT values were compared with
      EELVO2 using Bland-Altman analysis and Pearson correlation. RESULTS: Limits of
      agreement ranged from -0.83 to 1.31 l. Pearson correlation revealed significant
      results. There was no significant impact of RM or NRM on EELVO2-EELVEIT
      relationship (p=0.21; p=0.23). DISCUSSION: During typical routine respiratory
      manoeuvres like endotracheal suctioning or alveolar recruitment, EELV cannot be
      estimated by EIT with reasonable accuracy.

PMID- 24114892
TI  - An exploration of adolescent nonsuicidal self-injury and religious coping.
AB  - Many adolescents who engage in nonsuicidal self-injury (NSSI) self-identify as
      religious, but the role of religion in their NSSI is not known. This exploratory
      study examined the relationship between religious coping and religiousness among
      adolescents who self-injure and the function of their NSSI. Thirty adolescents
      aged 12-19 years who had engaged in NSSI participated in an interview and
      completed questionnaires. Multiple regressions were used to examine the
      relationship between religious coping and NSSI, and Pearson correlations were
      used to assess the relationship between religiousness and function of NSSI.
      Greater use of positive religious coping was associated with lower likelihood of
      engaging in NSSI to rid oneself of unwanted emotions, whereas greater use of
      negative religious coping was associated with greater likelihood of engaging in
      NSSI for this reason as well as to avoid punishment or unwanted responsibility.
      Higher religiousness was associated with greater use of NSSI to communicate with
      or gain attention from others, whereas lower religiousness was associated with
      greater use of NSSI to relieve unwanted emotions. Having a greater understanding
      of how religious constructs are related to the various functions served by NSSI
      may inform treatment of this population, particularly among religious youth who
      self-injure.

PMID- 24114893
TI  - Awareness, acceptability, and use of female condoms among university students in
      Nigeria: implications for STI/HIV prevention.
AB  - BACKGROUND: Most university students in Nigeria are sexually active and engage in
      high risk sexual behaviors. The aim of this study was to assess the acceptability
      and use of female condoms in the context of HIV prevention in order to provide
      basic information that can stimulate female condom programming to promote
      sexually transmitted infection and HIV prevention among youths in tertiary
      institutions. MATERIALS AND METHODS: A descriptive, cross-sectional study was
      carried out among 810 undergraduate students of the University of Port Harcourt
      from October to November 2011, using a stratified sampling method and self
      administered questionnaires. RESULTS: Most of the students, 589 (72.7%) were
      sexually active; 352 (59.7%) reported having just one sexual partner, while 237
      (40.3%) had multiple partners. The mean number of sexual partners in the past six
      months was 2.2 +/- 0. Consistent condom use was reported among 388 (79.2%)
      students, 102 (20.8%) reported occasional usage, while 99 (16.8%) did not use
      condoms at all. Only 384 (65.2%) of the students had ever been screened for HIV.
      Although 723 (89.3%) were aware of female condoms, only 64(8.9%) had ever used
      one due to unavailability, high cost, and difficulty with its insertion.
      Nevertheless, 389 (53.8%) of the students expressed willingness to use them if
      offered, while 502 (69.4%) would recommend it to friends/peers. CONCLUSION: This
      study highlights significant challenges in the use of female condoms among
      university students. These include unavailability, high cost, and difficulty with
      insertion. Therefore, deliberate efforts using social marketing strategies,
      appropriate youth-friendly publicity, and peer education must be exerted to
      provide affordable female condoms and promote usage; such efforts should target
      vulnerable youths in Nigerian tertiary institutions.

PMID- 24114894
TI  - Body image satisfaction and self-esteem in Thai female adolescents: the
      moderating role of self-compassion.
AB  - AIM: Body image satisfaction significantly influences self-esteem in female
      adolescents. Increased reports of lowered satisfaction in this population have
      raised concerns regarding their compromised self-esteem. This research study,
      therefore, sought to identify a culturally significant moderator of the
      association between body image satisfaction and self-esteem in Thai female
      adolescents. Orientation toward self-compassion, found to be particularly high in
      Thailand, was examined. MATERIALS AND METHODS: A total of 302 Thai female
      undergraduates from three large public and private universities in the Bangkok
      metropolitan area responded to a set of questionnaires, which measured
      demographic information, body image satisfaction, self-compassion, and self
      esteem. Data were analyzed using correlation and multiple regression analyses.
      Self-compassion was tested as a moderator of the relationship between body image
      satisfaction and self-esteem. RESULTS: Although its effect was relatively small,
      self-compassion significantly moderated the positive relationship between body
      image satisfaction and self-esteem. The relationship became less stringent for
      those with high self-compassion. DISCUSSION: The cultivation of self-compassion
      was recommended in female adolescents. In addition to moderating the association
      between body image satisfaction and self-esteem, the benefits to health and well
      being of generalizing this cultivation are discussed.

PMID- 24114895
TI  - Suicide attempts and suicides in Bolivia from 2007 to 2012: pesticides are the
      preferred method - females try but males commit suicide!
AB  - BACKGROUND: Suicide attempts and suicides constitute a significant burden on
      communities and health systems, especially in low income countries. However, many
      low income countries lack epidemiological information on which to base future
      preventive strategies. This study reports on gender and age profiles as well as
      the likely background and means used for suicide attempts and suicides in
      Bolivia. METHOD: This study presents 1124 cases from four different sources of
      information: (i) emergency ward data with suicide attempts by poisoning from the
      year 2007, (ii) psychiatric ward data including suicide attempts from July 2011
      to July 2012, (iii) newspaper articles reporting attempted suicides and suicides
      from 2009 to 2011, and (iv) the National Statistics on Crime reporting suicides
      from the years 2010-2011. Data on age was stratified into three age groups:
      adolescents aged 10-19 years, young adults aged 20-29 years, and older adults
      aged above 29 years. Data from the hospital wards and Crime Statistics were
      pooled to compare characteristics of suicide attempts with suicides concerning
      age and gender. Data on age, gender, methods used, and reasons were analyzed
      using IBM SPSS version 21. RESULTS: Hospital data showed that more females
      (403/657, 61%) than males (254/657, 39%) attempted suicide, and females attempted
      suicide at a younger age than males (p<0.05). In contrast to this, more males
      (208/293, 70.5%) than females (85/293, 29.5%) committed suicide, and furthermore
      it was most prevalent among young adults aged 20-29 years of both genders, as
      observed from the Crime Statistics. The dominant method was pesticide poisoning
      varying from 400 out of 657 (70.5%) of the hospital poisoning cases to 65 out of
      172 (37.8%) of the newspaper cases. Newspaper data showed a higher mortality rate
      (65/77, 85.1%) among those using violent methods such as hanging and jumping
      compared to non-violent methods (43/84, 50.9%) such as ingesting chemicals and
      drugs (p<0.05). The reasons were related to interpersonal problems, economic
      problems, depression, and unwanted pregnancies. Many cases of suicide seemed to
      be hidden due to cultural and religious reasons. CONCLUSION: More females
      attempted suicide, whereas more males realized suicide. Suicide attempts were
      most numerous among adolescents in contrast to suicides being most prevalent in
      the older age groups. Self-poisoning with pesticides was the most popular method
      used. Access to potential suicide materials should be restricted and psychosocial
      interventions initiated to prevent suicides.

PMID- 24114896
TI  - Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case
      report.
AB  - Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder
      characterized by prematurity, hypogastric and upper leg swelling of various
      intensities, high serum estradiol and gonadotropin levels, and ovarian follicular
      cyst/cysts. In this paper, we present the first case of POHS presenting with
      vaginal bleeding. A female infant was born via spontaneous vaginal delivery at 25
      weeks of gestation with a birth weight of 610 g. At 36 weeks of post-conception
      age, she developed breast enlargement, swelling of the clitoral hood, labia major
      and minor, hypogastrium and upper legs. Several weeks later, vaginal bleeding
      started and lasted 3 days. The vaginal bleeding continued to occur at monthly
      intervals. The elevated levels of gonadotropins and estrogens, vulvar swelling
      and cysts in both ovaries confirmed the diagnosis of preterm ovarian
      hyperstimulation syndrome.

PMID- 24114897
TI  - Evaluation of bone mineral density in children with type 1 diabetes mellitus.
AB  - BACKGROUND: Factors such as vascular/neurological mechanisms, poor glycemic
      control, abnormalities in vitamin D/calcium, secondary hyperparathyroidism, and
      hypercalciuria have been blamed for the unfavorable effects of type 1 diabetes
      mellitus (type 1 DM) on bone health. In this present study, we aimed to evaluate
      the frequency of low bone mineral density (BMD) in children with type 1 DM.
      METHOD: Among 100 type 1 DM patients, a 25-hydroxy vitamin D level of <10 ng/mL
      was accepted as vitamin D deficiency and the level of 10-20 ng/dL was accepted as
      vitamin D insufficiency. BMD was measured, and Z-scores were evaluated according
      to adjusted Turkish standards. Participants with a Z-score of <=-2 were defined
      as having low BMD; BMD between -2 and -1 were defined as being in the low range
      of normality; and values >=-1 were accepted as normal. RESULTS: The vitamin D
      deficiency and insufficiency ratios were 28% and 43%, respectively. Low BMD and
      BMD in the low range of normality were diagnosed in 10% and 25% of patients,
      respectively. There was no difference in vitamin D, parathormone, and metabolic
      control levels between three groups: with normal BMD, low BMD, and BMD in the low
      range of normality. BMD Z-scores were not different between the pubertal and
      prepubertal groups. CONCLUSION: Detailed evaluation should be performed for BMD
      in the follow-up of DM to prevent complications by decreasing related risks.

PMID- 24114898
TI  - Neural mechanisms underlying chronic fatigue.
AB  - Fatigue is defined as a condition or phenomenon of declined ability and
      efficiency of mental and/or physical activities, caused by excessive mental or
      physical activities, diseases, or syndromes. Acute fatigue is a normal condition
      that disappears after a period of rest; in contrast, chronic fatigue does not
      disappear after an ordinary rest. Chronic fatigue impairs daily activities and
      contributes to various medical conditions and death. In addition, many people
      complain of chronic fatigue. It would thus be of great value to clarify the
      mechanisms underlying chronic fatigue and to develop efficient treatment methods
      to overcome it. Here, we review data primarily from behavioral,
      neurophysiological, and neuroimaging experiments related to the neural mechanisms
      underlying chronic fatigue. We propose that repetitive and prolonged overwork
      and/or stress cause neural damage of a facilitation system, as well as central
      sensitization and classical conditioning of an inhibition system. We also propose
      a new treatment strategy for chronic fatigue on the basis of its underlying
      neural mechanisms.

PMID- 24114899
TI  - Influence of Allium sativum extract on the hypoglycemic activity of
      glibenclamide: an approach to possible herb-drug interaction.
AB  - BACKGROUND: The use of herbs with allopathic medicines increases the possibility
      of herb-drug interaction, which may either be beneficial or harmful. Therefore,
      the present study was undertaken to determine the interaction of glibenclamide, a
      sulfonylurea, with the aqueous extract of garlic (Allium sativum), an herb used
      widely as an antidiabetic agent. METHODS: The interaction was evaluated by an
      acute study, chronic study, oral glucose tolerance test, and body weight
      estimation in streptozotocin-induced diabetic rats. Glibenclamide was given
      orally at two different doses of 0.25 and 0.5 mg/kg, and A. sativum extract (ASE)
      was administered at the dose of 500 mg/kg. Blood glucose level and body weight
      estimation were carried out at various intervals. RESULTS: The hypoglycemic
      effect observed with combinations of glibenclamide and ASE was greater than
      either of the drug given alone. Combined treatments of glibenclamide and ASE
      resulted in higher increase in body weight than alone treatments. CONCLUSIONS: We
      conclude that ASE shows a synergistic effect with glibenclamide. This could be
      important in reducing the dose of glibenclamide to achieve an enhanced
      therapeutic effect with minimal side effects.

PMID- 24114900
TI  - A population pharmacokinetic model of remifentanil in pediatric patients using
      body-weight-dependent allometric exponents.
AB  - BACKGROUND: Allometric exponents in population pharmacokinetic analysis are
      regularly used but the issue of fixing or estimating an allometric exponent
      remains controversial. The objective of the current analysis is to evaluate the
      performance of a body-weight-dependent allometric exponent (BDE) model of
      remifentanil. METHODS: The study was conducted in 34 patients (neonates to 17
      years and 2.5 to 97 kg body weight) following a single intravenous (IV) infusion
      of remifentanil (5 MUg/kg). A population pharmacokinetic approach was taken to
      describe drug clearance by the following BDE equation: CL=CLpop(BW/14.6 kg)L*BW(
      M). Three allometric models were used to explore the impact of allometric
      exponents on the total clearance of remifentanil. RESULTS: All model-fitted
      structural, covariate, and statistical parameters were estimated with good to
      excellent precision (%RSE). However, on the basis of calculated Akaike weights
      (0.000 for model 1, 0.004 for model 2, and 0.996 for model 3), model 3 is the
      most robust model to describe individual clearance estimates. CONCLUSIONS: The
      BDE model performed best for the estimation of remifentanil clearance and is
      realistic and of practical value. Further investigation should be conducted for
      such models.

PMID- 24114901
TI  - Evaluation of partial area under the concentration time curve to estimate
      midazolam apparent oral clearance for cytochrome P450 3A phenotyping.
AB  - BACKGROUND: Midazolam apparent oral clearance (CLORAL) is used to estimate
      intestinal and hepatic cytochrome P450 (CYP) 3A activity. A limited sampling
      approach was performed to access a midazolam partial area under the concentration
      time curve (AUC) to estimate CLORAL. METHODS: Midazolam plasma concentrations
      from healthy adults were obtained during CYP3A baseline (n=116), inhibition
      (n=75), and induction or activation (n=66) from seven published studies. Observed
      CLORAL and partial AUCs of AUC0-2, AUC0-4, AUC0-6, AUC1-2, AUC1-4, AUC2-4, and
      AUC2-6 were determined by noncompartmental analysis. Subject data were randomly
      divided into a training set and a validation set. Linear regression equations,
      derived from partial AUCs, were developed from training set data. Predicted
      CLORAL was determined from these equations from validation set data. Preset
      criterion was a coefficient of determination (r2) greater than or equal to 0.9.
      Bias and precision were evaluated by relative percent mean prediction error
      (%MPE) and relative percent mean absolute error (%MAE). RESULTS: During CYP3A
      baseline conditions, all of the evaluated CLORAL equations had unacceptable r2
      (range: 0.34-0.86). During CYP3A inhibition, all of the evaluated CLORAL
      equations had unacceptable %MAE. Acceptable r2, %MPE, and %MAE were observed
      during CYP3A induction/activation with AUC0-4 (r2=0.99, %MPE=3.9, %MAE=12.5) and
      AUC1-4 (r2=0.99, %MPE=6%, %MAE=11.1%). The same equations also predicted the
      extent of CYP3A induction as a lack of equivalence was observed with AUC0-4 and
      AUC1-4. CONCLUSIONS: Midazolam partial AUCs were unable to estimate CYP3A
      activity during the evaluated baseline and inhibitory conditions. Midazolam
      CLORAL utilizing a partial AUC0-4 and AUC1-4 was able to estimate CYP3A induction
      with rifampin and Ginkgo biloba extract.

PMID- 24114902
TI  - Measuring cardiopulmonary parameters during dual-task while walking.
AB  - BACKGROUND: The purpose of the present study was to examine the metabolic cost of
      dual-task performance of a cognitive task while walking under two conditions:
      comfortable and fast gait speed. METHODS: Twenty-five healthy young adults
      (25.7+/-3.05 years) walked over-ground at a comfortable self-selected speed and
      on a treadmill at a fast speed with and without performing a cognitive task.
      Cardiopulmonary parameters were measured by the metabolic K4b2 system, gait
      parameters were measured with GaitRite and cognitive performance was expressed as
      percentage of correct answers to a set of riddles. RESULTS AND CONCLUSIONS:
      During rest, cognitive load resulted in a metabolic cost indicated by a
      significant increase in VO2 (p<0.01). Breathing rate increased significantly
      during dual-tasking in both walking conditions (p<0.01 for both). Fifty-two
      percent of the participants decreased gait speed during the dual-task condition
      while walking over-ground, accompanied by a significant decrease in tidal volume
      (p<0.01) without a decrease in breathing and heart rates. More than 70% of the
      participants improved or maintained their cognitive performance while walking
      (over-ground, 72% and treadmill, 75%), independently from the alterations in gait
      speed. The current findings confirm that mental processing increases energy
      demands while sitting. In addition, the results contribute new insight into dual
      task paradigm research, by showing that breathing rate is sensitive to an
      additional cognitive load while walking, even in young healthy adults. Moreover,
      the participants were able to adjust the strategy they used to cope with
      cognitive load while walking over-ground when gait speed was imposed.

PMID- 24114903
TI  - Temporal expression of IL-1beta and IL-10 in rat skin, muscle, small bowel, and
      colon wounds: a correlative study.
AB  - BACKGROUND: Cytokines play a major role in coordinated wound healing events. We
      hypothesized that rapid intestinal healing is due to an early upregulation of the
      pro-inflammatory cytokine interleukin-1beta (IL-1beta), followed by increases in
      the expression of the anti-inflammatory cytokine IL-10. METHODS: We characterized
      the time course of IL-1beta and IL-10 release at four wounds (skin, muscle, small
      bowel, and colonic anastomosis) after surgery on 38 juvenile male Sprague-Dawley
      rats. The tissue samples of each site were harvested at 0 (control), 1, 3, 5, 7,
      and 14 days postoperatively (n=6-8 per group) and analyzed by enzyme-linked
      immunosorbent assay kits for IL-1beta and IL-10. RESULTS: IL-1beta expression
      peaked at days 5 and 7 in small bowel and colonic wounds when compared to skin or
      muscle. Similarly, IL-10 showed high expression in these time points in small
      bowel and colonic wounds. However, IL-10 showed the same expression in all time
      points in muscle and skin tissues except at day 1. CONCLUSIONS: The high
      expression in IL-1beta and IL-10 levels in small bowel and colon might explain
      the accelerated healing process in these wounds in comparison to skin and muscle
      tissues. Additional studies are required to determine whether IL-1beta and IL-10
      expression is the major factor defining site-specific differences in healing
      rates in different tissues. Understanding cytokine action in the wound healing
      process could lead to novel and effective therapeutic strategies.

PMID- 24114904
TI  - Ameliorative effect of diallyl trisulphide on arsenic-induced oxidative stress in
      rat erythrocytes and DNA damage in lymphocytes.
AB  - BACKGROUND: Arsenic (As) is a naturally occurring semimetallic element that is
      classified as a toxicant and a human carcinogen. Diallyl trisulphide (DATS), an
      organosulphur compound, is an antioxidative substance that is extracted from
      garlic (Allium sativum). Erythrocytes are very expedient models to understand the
      susceptibility of membrane to oxidative damage induced by different xenobiotic
      compounds. Arsenic has been reported to induce oxidative stress to erythrocytes
      due to lipid peroxidation and alteration in defence mechanism as erythrocytes are
      the first target that arsenic compounds attack in the body after systemic
      absorption. In the light of this fact, the purpose of this study is to
      characterise the ameliorative effect of DATS on arsenic-induced oxidative stress
      in rat erythrocytes. METHODS: Experimental rats were randomly divided into four
      groups and treated orally for 28 days: control, As [5 mg/kg body weight (BW)]
      treated, As+DATS (80 mg/kg BW) treated, DATS (80 mg/kg BW) treated and As+vitamin
      C (100 mg/kg BW) treated. Oxidative stress in erythrocytes was recorded by
      estimating plasma marker enzymes, plasma and erythrocyte membrane oxidative
      stress markers, erythrocyte membrane antioxidant enzymes and non-antioxidant
      enzymes, etc. RESULTS: Oral administration of arsenic at 5 mg/kg BW per day
      elevated the levels of plasma marker enzymes, namely, aspartate transaminase
      (AST), alanine transaminase (ALT), acid phosphatase (ACP), alkaline phosphatase
      (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (gammaGT)
      (U/L) with significantly increased lipid peroxidation markers such as
      thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), lipid
      hydroperoxides (LH), conjugated dienes (CD), and protein carbonyl (PC) contents
      were also elevated in As-treated rat plasma and erythrocytes. The levels of non
      enzymatic antioxidants (reduced glutathione, vitamins C and E) and enzymatic
      antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR),
      and glucose-6-phosphate dehydrogenase (G6PD) were also decreased in As-treated
      rats. The toxic effect of As significantly decreased the activities of membrane
      bound ATPases (Na+/K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase), with a significant
      increase in% tail DNA of rat lymphocytes measured by means of a single-cell gel
      electrophoresis assay. Administration of DATS for 28 days significantly reduced
      the levels of plasma markers. The levels of TBARS, MDA, LH, CD, and PC were
      significantly decreased and there was a significant increase in ATPase activities
      and non-enzymatic and enzymatic antioxidants on treatment with DATS in a dose
      related manner. CONCLUSIONS: All these changes were supported by reduction of DNA
      damage in lymphocytes with DATS treatment. DATS at a dose of 80 mg/kg BW was
      found to be most effective and the results revealed the same. The results of the
      study showed that DATS shows a protective effect against As-induced oxidative
      stress in rat erythrocytes and lymphocytes.

PMID- 24114905
TI  - Distribution of performance-related gene polymorphisms (ACTN3 R577X and ACE ID)
      in different ethnic groups of the Indian Army.
AB  - BACKGROUND: India has a heterogeneous geographical location with varying ethnic
      groups with distinct genetic pools. Polymorphisms R577X and insertion/deletion
      (I/D), occurring in alpha-actinin3 (ACTN3) and angiotensin converting enzyme
      (ACE) genes, respectively, are reportedly associated with sprint and endurance
      performance. The normative genetic background of a population provides the
      baseline genetic diversity of the population. METHODS: We investigated the
      distribution of R577X and I/D polymorphisms in four Indian ethnic populations
      employed in the Indian Army that requires high levels of physical fitness. A
      total of 598 army subjects with four different ethnicities were recruited for the
      study: Rajputs, South Indians, Gorkhas, and Ladakhis. Genotyping was performed
      using polymerase chain reaction-restriction fragment length polymorphism followed
      by statistical analysis. RESULTS: The present study reports for the first time
      the genotypic distribution of ACTN3 R577X polymorphism in four ethnic groups of
      the Indian population with no significant change in distribution of R and X
      alleles among these groups and their overall percentage bearing similarity with
      the Caucasian population. ACE I/D polymorphism showed significant differences
      between Rajputs and Gorkhas, Rajputs and Ladakhis, Gorkhas and South Indians, and
      South Indians and Ladakhis. Combined genotypic analysis showed the highest
      frequencies of ID+RX in all ethnic groups. CONCLUSIONS: Our study reports the
      genetic predominance of ACE I allele in Gorkhas and I allele predominance in
      Ladakhis for the first time, thus suggesting that they could be better endurance
      performers. Both these ethnic groups evolved from the Mongolian race and hence
      could have similar genotypic distribution. This study provides a comparative
      account of the Indian normative genetic data in performance-related genes.

PMID- 24114906
TI  - Hematological profile in neonatal jaundice.
AB  - BACKGROUND: Neonatal morbidity due to neonatal jaundice is an alarming situation,
      which needs to be detected and managed at the earliest possible. Many different
      etiologies come into play together, and at times, it is difficult to isolate the
      cause of neonatal jaundice. Certain diagnostic tests such as hemoglobin levels,
      reticulocyte count, leukocyte count, and blood grouping might hasten the
      diagnosis. This study analyzes the different parameters of hematological profile
      and how they influence the various etiologies of neonatal jaundice. METHODS: One
      hundred jaundiced neonates admitted to the pediatric care unit of MKCG Medical
      Hospital, Odisha, were considered as subjects for this study. Blood tests were
      done, and accordingly, the neonates were grouped into three depending on the
      leukocyte count, reticulocyte count, and hemoglobin levels. Blood grouping of
      mother and baby was done to see the pattern of ABO incompatibility. RESULTS:
      Physiological jaundice cases showed no significant variations in hematological
      profile, while jaundice due to ABO incompatibility, septicemia, Rh
      incompatibility, intracranial hemorrhage, and G6PD deficiency had anemia,
      reticulocytosis, and leukocytosis. CONCLUSIONS: The results can be used for early
      and simple investigation method for the diagnosis of neonatal jaundice.

PMID- 24114907
TI  - Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and
      kwashiorkor based on breath test.
AB  - BACKGROUND: Hepatic metabolism of drugs has been rarely studied in children with
      malnutrition. Caffeine breath test (CBT) has been used to determine the activity
      of cytochrome P450 1A2 (CYP1A2) enzymes in children. We used the CBT to assess
      how marasmus and kwashiorkor differentially affect 13C-caffeine metabolism.
      METHODS: A total of 45 children composed of 15 children per group of malnutrition
      (marasmus, marasmic-kwashiorkor, and kwashiorkor) were studied during
      malnutrition and after nutritional recovery. After an overnight fast, patients
      ingested 3 mg/kg 13C-caffeine at 0900 h. Duplicate breath samples were collected
      into an Exetainer bottle at -20, -10, and -1 min and at 15-min intervals for 2 h.
      The mean cumulative percent dose recovered (CPDR) of 13C-caffeine in the expired
      13CO2 was determined over the study period. RESULTS: The CPDR in the expired
      13CO2 in 2 h significantly increased after nutritional recovery in children with
      marasmus (from 6.80%+/-3.00% to 7.67%+/-2.81%; Student's t-test, p=0.001),
      marasmic-kwashiorkor (from 6.61%+/-2.26% to 7.56%+/-2.46%, p=0.041), and
      kwashiorkor (from 6.29%+/-1.06% to 7.20%+/-1.80%, p=0.002). When the three groups
      of malnutrition were compared, there was no significant difference in their mean
      CPDR in 2 h during malnutrition [p=0.820, analysis of variance (ANOVA)] and after
      nutritional recovery (p=0.810, ANOVA). CONCLUSIONS: Hepatic metabolism of
      caffeine significantly decreased in children with marasmus, marasmic-kwashiorkor,
      and kwashiorkor compared to after they had recovered nutritionally. This suggests
      a decreased CYP1A2 activity in all categories of malnutrition.

PMID- 24114908
TI  - Evaluation of antiulcerogenic potential of antioxidant alpha-tocopherol in
      pylorus-ligated albino rats.
AB  - BACKGROUND: Oxidative free radicals and lipid peroxidation mediate gastric
      injury. alpha-Tocopherol is a redox agent with biological and antioxidant
      property, hence, may provide ulcer protection. METHODS: Pylorus-ligated Shay rats
      (n=6) were used as the experimental gastric ulcer animal model. The rats were
      divided into three groups. Group I received saline (5 mL/kg), Group II alpha
      tocopherol (12.5 mg/kg), and Group III omeprazole (3.6 mg/kg), orally daily for 5
      days prior to ulcerogenic challenge. Nineteen hours after the challenge, the rats
      were sacrificed and their stomachs isolated and studied for degree of gastric
      injury. Formed gastric juice was collected for measurement of volume, titrimetric
      estimation of free and total acidity, and total acid output by the conventional
      methods. The ulcer index and total acid outputs were calculated. RESULTS: alpha
      Tocopherol exerted significant (p<0.05) antiulcer activity (the ulcer index was
      reduced to 7.4 +/- 1.0 from the control value of 19.8 +/- 4.1). alpha-Tocopherol
      also significantly reduced free and total acidity, gastric juice volume, and
      total acid output (p<0.01). The results were analyzed by ANOVA and Scheffe's
      multiple comparison test. CONCLUSIONS: The study demonstrates that alpha
      tocopherol has significant antiulcer activity. It, perhaps, acts by decreasing
      hydrochloric acid output.

PMID- 24114909
TI  - Arrhythmogenesis after acute myocardial necrosis with and without preceding
      ischemia in rats.
AB  - BACKGROUND: The relative role of acute myocardial ischemia and infarction in
      ventricular arrhythmogenesis is incompletely understood. We compared the
      arrhythmia pattern after ischemia/infarction to that observed after direct
      myocardial necrosis without preceding ischemia in rats. METHODS: Coagulation
      necrosis was induced in Wistar rats (n=20, 280+/-3 g) by radiofrequency current
      application (for 15 s) from a 4-mm-tip ablation catheter. Myocardial infarction
      was induced by coronary artery ligation with (n=10) or without (n=10)
      reperfusion. Using 24-h telemetry recording, we examined ventricular arrhythmias,
      voluntary motor activity and indices of sympathetic activation. RESULTS: The
      coagulation-necrosis volume was 24.4%+/-0.6%, comparable to the infarct size in
      the absence of reperfusion. Acute left ventricular failure and sympathetic
      activation were similar in the three groups. Coagulation necrosis induced
      ventricular fibrillation immediately, followed by a second peak after ~1 h.
      Reperfusion decreased ventricular arrhythmias, whereas a second arrhythmogenic
      period (between the third and the eight hour) was noted in non-reperfused
      infarcts (mainly monomorphic ventricular tachycardia). CONCLUSIONS: Distinct
      arrhythmia patterns occur after myocardial infarction (with or without
      reperfusion) and after direct necrosis. They are not produced by differences in
      sympathetic activation and are likely related to the evolution of myocardial
      injury. The necrosis rat model may be useful in studies of arrhythmogenesis.

PMID- 24114911
TI  - Clinical sample stability and measurement uncertainty.

PMID- 24114912
TI  - Comparison of two immunoassays for measurement of faecal calprotectin in
      detection of inflammatory bowel disease: (pre)-analytical and diagnostic
      performance characteristics.
AB  - BACKGROUND: Symptoms of inflammatory bowel disease (IBD) and irritable bowel
      syndrome (IBS) can overlap. Faecal calprotectin has recently been established to
      be a non-invasive marker for neutrophilic intestinal inflammation. We compared
      two devices for extraction of faecal calprotectin. Based on these results, two
      immunoassays for measurement of faecal calprotectin were evaluated. METHODS:
      Samples were extracted using the Thermo Fisher extraction device (Thermo Fisher
      Scientific) and Smart Pep extraction device (Roche Diagnostics) and measured with
      the EliA Calprotectin immunoassay (Thermo Fisher Scientific) on ImmunoCAP 250.
      The performance of both assays was investigated by enrolling 183 consecutive
      patients (79 males, 104 females; median age 32 years) with clinical suspicion of
      IBD. Faecal calprotectin was measured using a recently launched immunoassay, EliA
      Calprotectin in comparison with an established immunochomatographic point-of-care
      test (POCT, Quantum Blue Calprotectin; Buhlmann). Results were compared with
      endoscopic and histological findings. RESULTS: The use of the Thermo Fisher
      extraction device resulted in an underestimation of faecal calprotectin
      concentrations, especially in liquid stool samples. IBD was diagnosed in 51/183
      patients (27.9%) [Crohn's disease (CD, n=37), ulcerative colitis (UC, n=14)].
      After adjusting the optimal cut-off for detection of IBD using receiver operating
      curve analysis, a sensitivity of 94.1% and 90.2% and specificity of 87.9% and
      90.9% for the EliA and POCT assay, respectively, were obtained. CONCLUSIONS: The
      Thermo Fisher device is not reliable for extraction of faecal calprotectin. The
      performance characteristics of the EliA Calprotectin assay are statistically
      equivalent to the Buhlmann POCT.

PMID- 24114913
TI  - Multicenter method evaluation of the ARKTM Methotrexate Immunoassay.

PMID- 24114910
TI  - Septin functions in organ system physiology and pathology.
AB  - Human septins comprise a family of 13 genes that encode for >30 protein isoforms
      with ubiquitous and tissue-specific expressions. Septins are GTP-binding proteins
      that assemble into higher-order oligomers and filamentous polymers, which
      associate with cell membranes and the cytoskeleton. In the last decade, much
      progress has been made in understanding the biochemical properties and cell
      biological functions of septins. In parallel, a growing number of studies show
      that septins play important roles for the development and physiology of specific
      tissues and organs. Here, we review the expression and function of septins in the
      cardiovascular, immune, nervous, urinary, digestive, respiratory, endocrine,
      reproductive, and integumentary organ systems. Furthermore, we discuss how the
      tissue-specific functions of septins relate to the pathology of human diseases
      that arise from aberrations in septin expression.

PMID- 24114914
TI  - Measurement of amino terminal propeptide of type III procollagen (PIIINP)
      employing the ADVIA Centaur platform. Validation, reference interval and
      comparison to UniQ RIA.
AB  - BACKGROUND: Recently, measurement of amino terminal propeptide of type III
      procollagen (PIIINP) was introduced as a part of the hepatic cirrhotic marker
      enhanced liver fibrosisTM test on the automated ADVIA Centaur((r)) immunoassay
      platform (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA). In this
      article, we show that the Centaur PIIINP may be used in place of the much more
      labor-intensive RIA method, and we present an age stratified reference interval.
      METHODS: We analyzed four control samples 20 times over a period of 5 days.
      Centaur PIIINP assay measurements were compared with the widely used UniQ PIIINP
      RIA assay (Orion Diagnostica, Espoo, Finland) using 55 patient samples (range=3.7
      43.3 ug/L). Furthermore, we established a reference interval based on samples
      from 287 blood donors. RESULTS: In the concentration range 2.5-11.9 ug/L, the
      total imprecision was below 8%. Comparison with the UniQ PIIINP RIA assay
      yielded: Centaur PIIINP ug/L = 1.9 * (UniQ PIIINP RIA) + 0.6 ug/L, r2=0.94. The
      reference interval for the Centaur PIIINP assay showed no gender difference but
      was stratified by age [4.0-11.0 ug/L (18-40 years) and 3.5-9.5 ug/L (41-70
      years)]. CONCLUSIONS: We conclude that the Centaur PIIINP assay is suitable for
      routine use with our newly defined reference interval. The results obtained by
      Centaur correlates well with those obtained by the previously employed RIA,
      though the absolute values are higher.

PMID- 24114915
TI  - Estimation of uncertainty in measurements in the clinical laboratory.

PMID- 24114916
TI  - Is magnetic resonance imaging really innocent?

PMID- 24114917
TI  - Vulnerability of point-of-care test reagents and instruments to environmental
      stresses: implications for health professionals and developers.
AB  - Strategic integration of point-of-care (POC) diagnostic tools during crisis
      response can accelerate triage and improve management of victims. Timely
      differential diagnosis is essential wherever care is provided to rule out or rule
      in disease, expedite life-saving treatment, and improve utilization of limited
      resources. POC testing needs to be accurate in any environment in which it is
      used. Devices are exposed to potentially adverse storage and operating
      conditions, such as high/low temperature and humidity during emergencies and
      field rescues. Therefore, characterizing environmental conditions allows
      technology developers, operators, and responders to understand the broad
      operational requirements of test reagents, instruments, and equipment in order to
      improve the quality and delivery of care in complex emergencies, disasters, and
      austere environmental settings. This review aims to describe the effects of
      environmental stress on POC testing performance and its impact on decision
      making, to describe how to study the effects, and to summarize ways to mitigate
      the effects of environmental stresses through good laboratory practice,
      development of robust reagents, and novel thermal packaging solutions.

PMID- 24114918
TI  - A soluble form of the macrophage-related mannose receptor (MR/CD206) is present
      in human serum and elevated in critical illness.
AB  - BACKGROUND: This study tests the hypothesis that the mannose receptor (MR/CD206),
      which is expressed primarily by macrophages and dendritic cells, can be found in
      a soluble form (sMR, sMR) in human serum. Furthermore, we wished to establish and
      validate an enzyme-linked immunosorbent assay (ELISA) for sMR and to perform
      initial studies exploring the potential of sMR as a biomarker. METHODS: Western
      blotting identified a single band of approximately 170 kDa in human serum, and
      MALDI MS/MS of the purified protein confirmed it to be sMR. An ELISA was
      established and validated with a measurement range of 1-256 ug/L. RESULTS: The
      95% reference interval was 0.10-0.43 mg/L based on measurements of serum samples
      from healthy individuals (n=217). Samples from hospitalised patients (n=219)
      revealed that more than 50% of patients had concentrations above 0.43 mg/L. Very
      high concentrations (up to 6.2 mg/L) were observed in critically ill patients
      with sepsis and/or severe liver disease. CONCLUSIONS: This study documents, for
      the first time, the presence of sMR in human serum and describes an optimised
      ELISA suitable for quantitative measurements. Levels of sMR are strongly elevated
      in several disease states, including sepsis and liver disease, and the protein
      therefore shows promise as a new biomarker.

PMID- 24114919
TI  - Reference change values to assess changes in concentrations of biomarkers of
      exposure in individuals participating in a cigarette-switching study.
AB  - BACKGROUND: In a previous clinical study, levels of biomarkers of exposure (BoEs)
      for specific toxicants were significantly reduced in smokers who switched from
      conventional cigarettes to reduced toxicant prototype (RTP) cigarettes. Very
      little is known about the biological variability of tobacco smoke BoEs within
      individuals and sub-groups, and the descriptive group-comparison statistics might
      not be sufficient to understand such changes. Therefore, we assessed how
      different statistical methods could be used to interpret changes in urine BoE
      levels at the individual level. METHODS: We used non-parametric statistical
      reference limits, the empirical rule and reference change values (RCVs) to assess
      changes in levels of BoEs related to four toxicants in cigarettes smoke. Current
      smokers [of 6 mg and 1 mg International Organization for Standardization (ISO)
      tar yields] were allocated to switching to RTP groups or non-switching control
      groups within their respective tar bands. There were two 6 mg tar study groups,
      with a non-switching group (CC6, n=46) and a group switching to an RTP containing
      tobacco-substitute sheet and modified filter (TSS6, n=49); and three 1 mg tar
      smoker groups, with one non-switching (CC1, n=42), a group switching to an RTP
      containing tobacco-substitute sheet and modified filter (TSS1, n=44) and one
      switching to an RTP containing an enzyme-treated tobacco and modified filter
      (BT1, n=47). RESULTS: Assessment of the direction of change showed that up to the
      100% of subjects experienced a decrease in levels of some BoEs. Between 49% and
      64% of subjects in the switching groups were classified as having decreased
      levels of 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) by the non-parametric
      criterion, whereas only 2%-6% had reduced levels of N-nitrosoanatabine (NAT). Of
      non-switchers, in 7%-14% of those smoking 1 mg ISO tar yield cigarettes increases
      were classified across all BoEs. RCVs highlighted patterns with more detail,
      showing that most changes occurred within 14 days of switching. Among smokers who
      switched to 6 mg RTPs, 40%, 44%, 6% and 15%, respectively, were classified as
      experiencing significant decreasing levels of HPMA, 3-hydroxypropylmercapturic
      acid, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and NAT, whereas in the two 1
      mg switching groups 46%, 22%, 11% and 52% and 43%, 27%, 2% and 16% had decreased
      levels of the same biomarkers. Up to five subjects in the 6 mg non-switching
      group were classified as having increased levels of all BoEs. CONCLUSIONS:
      Although we believe that is not possible to determine whether the observed
      changes in BoEs reflect biological relevance, the use of reference values enables
      assessment of changes in BoEs at the individual level. Estimates of the BoE
      variability between subjects might aid study design and setting minimum targets
      for smoke toxicant yields for future development of RTPs.

PMID- 24114920
TI  - Volumetric analysis of endoscopic and traditional surgical approaches to the
      infratemporal fossa.
AB  - OBJECTIVES/HYPOTHESIS: In an effort to decrease morbidity, skull base surgeons
      have explored less invasive approaches to the infratemporal fossa, including
      endonasal-endoscopy, minicraniotomies, and transantral endoscopic and microscopic
      corridors. This project presents quantitative data that assesses the
      practicality, and volumetric exposure afforded by endonasal and open approaches
      to the infratemporal fossa. STUDY DESIGN: First, the study defines the anatomy of
      endoscopic-endonasal and preauricular approaches to the infratemporal fossa.
      Subsequently, the study involved the calculation of anatomical volumes using
      cadaveric and virtual models. METHODS: Computed tomography (CT) scanning of two
      anatomical specimens served to recreate computer simulations of the endonasal and
      preauricular approaches, allowing for the assessment of the infratemporal fossae
      volumes. In addition, the dissections served to identify and mark critical
      surgical landmarks and boundaries. A second CT scan, after the surgical
      dissection, allowed for a reanalysis of the data for a volumetric comparison of
      the surgical approaches. RESULTS: Pre- and postdissection CT scans and computer
      simulations revealed that volumes in the open and endonasal approaches to the
      infratemporal fossa are strikingly similar, suggesting that volumes of surgical
      instrumentation and visualization may also be comparable. However, the entry gate
      for instrumentation differed significantly for each approach. CONCLUSION: This
      study suggests that, although the entry gate for instrumentation is greater
      during an open approach, contrary to intuition, an open approach does not create
      a substantially larger working space or visual field. Analysis of volumetric
      measurements facilitates a better understanding of the indications for each
      procedure.

PMID- 24114921
TI  - Water compatible multicomponent cascade Suzuki/Heck-aldol, Suzuki-aldol-Suzuki,
      and aldol-Suzuki-aldol reactions: an ecofriendly paradigm for multiple carbon
      carbon bond formation in one pot.

PMID- 24114922
TI  - Hot-melt granulation in a twin screw extruder: effects of processing on
      formulations with caffeine and Ibuprofen.
AB  - Hot-melt granulation (HMG) by twin screw extrusion is a novel technology for the
      continuous processing of pharmaceuticals but confidence must still be gained
      regarding whether the environment affects drug properties. In this preliminary
      study, granulation was studied for a model product containing lactose monohydrate
      and active ingredients of differing water solubility, namely ibuprofen versus
      caffeine. The formulations were granulated at 220 rpm and 100 degrees C with
      polyethylene glycol binders of differing molecular weights and at concentrations
      between 6.5% and 20%. In terms of granule properties, the low melting point of
      ibuprofen had a dominant influence by producing larger, stronger granules,
      whereas the caffeine products were more comparable to a blank containing no
      active ingredient. Drug degradation was study by differential scanning
      calorimetry, X-ray diffraction, and high-pressure liquid chromatography. The only
      detected change was the dehydration of lactose monohydrate for the caffeine and
      blank products, whereas the lubricating influence of the ibuprofen protected its
      granules. The short residence time (~60 s) was consider to be influential in
      minimizing damage of the drug despite the high temperature and shear attributed
      to HMG inside a twin screw extruder.

PMID- 24114923
TI  - Mirror-image organometallic osmium arene iminopyridine halido complexes exhibit
      similar potent anticancer activity.
AB  - Four chiral Os(II) arene anticancer complexes have been isolated by fractional
      crystallization. The two iodido complexes, (S(Os),S(C))-[Os(eta(6)-p
      cym)(ImpyMe)I]PF6 (complex 2, (S)-ImpyMe: N-(2-pyridylmethylene)-(S)-1
      phenylethylamine) and (R(Os),R(C))-[Os(eta(6)-p-cym)(ImpyMe)I]PF6 (complex 4, (R)
      ImpyMe: N-(2-pyridylmethylene)-(R)-1-phenylethylamine), showed higher anticancer
      activity (lower IC50 values) towards A2780 human ovarian cancer cells than
      cisplatin and were more active than the two chlorido derivatives, (S(Os),S(C))
      [Os(eta(6)-p-cym)(ImpyMe)Cl]PF6, 1, and (R(Os),R(C))-[Os(eta(6)-p
      cym)(ImpyMe)Cl]PF6, 3. The two iodido complexes were evaluated in the National
      Cancer Institute 60-cell-line screen, by using the COMPARE algorithm. This showed
      that the two potent iodido complexes, 2 (NSC: D-758116/1) and 4 (NSC: D
      758118/1), share surprisingly similar cancer cell selectivity patterns with the
      anti-microtubule drug, vinblastine sulfate. However, no direct effect on tubulin
      polymerization was found for 2 and 4, an observation that appears to indicate a
      novel mechanism of action. In addition, complexes 2 and 4 demonstrated potential
      as transfer-hydrogenation catalysts for imine reduction.

PMID- 24114924
TI  - Engineering liver tissue from induced pluripotent stem cells: a first step in
      generating new organs for transplantation?

PMID- 24114925
TI  - Autoantibodies from long-lived 'memory' plasma cells of NZB/W mice drive immune
      complex nephritis.
AB  - OBJECTIVES: We have previously shown that both short- and long-lived plasma cells
      (PCs) significantly contribute to autoantibody production in NZB/W mice as a
      model of lupus nephritis. The aim of this study was to determine the role of
      autoreactive long-lived (memory) PCs refractory to immunosuppression and B cell
      depletion in the pathogenesis of systemic lupus erythematosus. METHODS: Splenic
      CD138+ antibody-secreting cells (ASCs) from >6-month-old NZB/W mice with high
      titres of anti-dsDNA autoantibodies or from Balb/c mice 5 days after secondary
      immunisation with ovalbumin (OVA) were adoptively transferred to immunodeficient
      Rag1(-/-) mice, in which the development of nephritis was investigated by
      measuring proteinuria. Total IgG and IgM as well as anti-dsDNA and anti-OVA
      antibody levels were followed up by ELISA. After 21 weeks the recipient mice were
      sacrificed so that PCs in spleen and bone marrow could be analysed using ELISPOT
      and flow cytometry and renal immunohistology performed. RESULTS: The adoptive
      transfer of NZB/W and anti-OVA ASCs resulted in the continuous generation of anti
      dsDNA antibodies and anti-OVA antibodies, respectively, exclusively by long-lived
      PCs that had homed to the spleen and bone marrow of recipient Rag1(-/-) mice.
      Rag1(-/-) mice generating autoantibodies including anti-dsDNA had reduced
      survival, proteinuria and immune complex nephritis with C1q, C3, IgG and IgM
      deposits 21 weeks after transfer. CONCLUSIONS: These findings demonstrate that
      autoantibodies exclusively secreted by long-lived (memory) PCs contribute to
      autoimmune pathology and should be considered as candidate targets for future
      therapeutic strategies.

PMID- 24114926
TI  - Postdischarge international normalized ratio testing and long-term clinical
      outcomes of patients with heart failure receiving warfarin: findings from the
      ADHERE registry linked to Medicare claims.
AB  - BACKGROUND: Effective warfarin thromboprophylaxis requires maintaining
      anticoagulation within the recommended international normalized ratio (INR)
      range. INR testing rates and associations between testing and outcomes are not
      well understood. HYPOTHESIS: INR testing rates after hospitalization for acute
      decompensated heart failure are suboptimal, and testing is associated with lower
      risks of mortality and adverse clinical events. METHODS: We conducted a
      retrospective cohort study of patients who were long-term warfarin users and were
      hospitalized for heart failure, had a medical history of atrial fibrillation or
      valvular heart disease, and were enrolled in fee-for-service Medicare. INR
      testing was defined as >=1 outpatient INR test within 45 days after discharge.
      Using Cox proportional hazards models, we examined associations between testing
      and all-cause mortality, all-cause readmission, and adverse clinical events at 1
      year. RESULTS: Among 8558 patients, 7722 (90.2%) were tested. After 1 year,
      tested patients had lower all-cause mortality (23.5% vs 32.6%; P < 0.001) and
      fewer myocardial infarctions (2.0% vs 3.3%; P = 0.02). These differences remained
      significant after multivariable adjustment with hazard ratios of 0.72 (95%
      confidence interval [CI]: 0.63-0.84; P < 0.001) and 0.58 (95% CI: 0.41-0.83; P =
      0.003), respectively. Differences in all-cause readmission, thromboembolic
      events, ischemic stroke, and bleeding events were not statistically significant.
      CONCLUSIONS: Postdischarge outpatient INR testing in patients with heart failure
      complicated by atrial fibrillation or valvular heart disease was high. INR
      testing was associated with improved survival and fewer myocardial infarctions at
      1 year but was not independently associated with other adverse clinical events.

PMID- 24114927
TI  - 1H and 13C NMR investigation of 20-hydroxyecdysone dioxolane derivatives, a novel
      group of MDR modulator agents.
AB  - The synthesis, structure elucidation and the complete (1)H and (13)C signal
      assignment of a series of dioxolane derivatives of 20-hydroxyecdysone,
      synthesized as novel modulators of multidrug resistance, are presented. The
      structures and NMR signal assignment were established by comprehensive one
      dimensional and two-dimensional NMR spectroscopy supported by mass spectrometry.

PMID- 24114928
TI  - Advance of CE and CEC in phytochemical analysis (2012-2013).
AB  - This article presents an overview of the advance of CE and CEC in phytochemical
      analysis, based on the literature not mentioned in our previous review papers
      [Chen, X. J., Zhao, J., Wang, Y. T., Huang, L. Q., Li, S. P., Electrophoresis
      2012, 33, 168-179], mainly covering the years 2012-2013. In this article,
      attention is paid to online preconcentration, rapid separation, and sensitive
      detection. Selected examples illustrate the applicability of CE and CEC in
      biomedical, pharmaceutical, environmental, and food analysis. Finally, some
      general conclusions and future perspectives are given.

PMID- 24114929
TI  - Altered inhibitory modulation of somatosensory cortices in paroxysmal kinesigenic
      dyskinesia.
AB  - BACKGROUND: The objective of this study was to clarify the excitability profiles
      of the somatosensory cortices in patients with paroxysmal kinesigenic dyskinesia.
      METHODS: Whole-head magnetoencephalography was used to record the somatosensory
      evoked fields elicited by paired-pulse electric stimulation of the median nerve
      in 15 patients with paroxysmal kinesigenic dyskinesia and in a control group of
      18 age-matched, healthy volunteers. Twelve of the patients were studied in both
      the drug-off and drug-on state. RESULTS: The paired-pulse inhibition ratios of
      the primary somatosensory cortical P35m responses and the secondary somatosensory
      cortical responses were significantly greater in drug-off patients with
      paroxysmal kinesigenic dyskinesia compared with either the drug-on patients or
      the control group. No significant difference in paired-pulse inhibition ratio was
      observed between the drug-on patients with paroxysmal kinesigenic dyskinesia and
      the control group. CONCLUSIONS: In patients with paroxysmal kinesigenic
      dyskinesia, intracortical inhibition of the primary and secondary somatosensory
      cortical areas is impaired, and the associated hyperexcitable phenomenon is
      modulatable by antiepileptic drugs.

PMID- 24114930
TI  - Close relationship between immunoglobulin secreting-cells and Epstein-Barr virus
      reservoir in patients infected with HIV.
AB  - Individuals infected with HIV have higher circulating Epstein-Barr virus (EBV)
      DNA load compared to healthy carriers. This study investigated whether level of
      spontaneous immunoglobulin secreting cells, one of the major hallmarks of HIV
      infection, is associated with an increase of EBV DNA load in PBMCs and the
      spontaneous EBV lytic cycle ex vivo in patients infected with HIV. Spontaneous
      virus production by cells infected with EBV and EBV DNA loads in PBMCs from which
      CD8(+) T-cells were removed were measured in 20 HIV-aviremic and 14 HIV-viremic
      patients. The number of circulating immunoglobulin-secreting cells (Ig-SCs) and
      CD8(+) T-lymphocyte activation were also investigated. Patients with detectable
      HIV RNA in plasma exhibited higher spontaneous ex vivo EBV secretion and higher
      levels of EBV DNA in PBMCs than their aviremic counterparts. In the two groups
      observed, a positive correlation was found between PBMCs EBV DNA viral load and
      Ig-SCs, CD38(bright) expression on CD8(+) T-cells and EBV DNA load in cell
      culture supernatants. These findings suggest that B-cell polyclonal activation
      and B-cell terminal differentiation into Ig-SCs may fuel EBV DNA reservoir and
      promote EBV production ex vivo in patients infected with HIV.

PMID- 24114931
TI  - Understanding TiO(2) size-dependent electron transport properties of a graphene
      TiO(2) photoanode in dye-sensitized solar cells using conducting atomic force
      microscopy.
AB  - Conducting AFM reveals a continuous conduction network of a TiO2 -graphene
      composite in DSSC due to a more intimate contact between the smaller sized TiO2 
      graphene composite nanosheets,which reduces the internal resistance at TiO2 /TiO2
      and TiO2 /FTO interfaces and ultimately leads to a faster and more efficient
      electron transport in the photoanode. 

PMID- 24114932
TI  - Gene regulation by glucocorticoid in ENaC-mediated Na+ transport by middle ear
      epithelial cells.
AB  - OBJECTIVES/HYPOTHESIS: The epithelial sodium channel (ENaC) is a Na(+) transport
      channel located in the apical membrane of the human middle ear epithelium.
      Although ENaC-mediated sodium transport has been reported to be upregulated by
      dexamethasone in human middle ear epithelium, there has been no study of the
      downstream pathways for increased ENaC expression mediated by glucocorticoids in
      this tissue. We investigated the effect of dexamethasone on the expression of
      ENaC and glucocorticoid regulatory genes for ENaC expression in human middle ear
      epithelial cells (HMEECs). STUDY DESIGN: In vitro investigation. METHODS: Real
      time RT-PCR and Western blot analysis were used to determine the expression level
      of ENaC and its regulatory genes in HMEECs. RESULTS: The transcript and protein
      expression of the alpha-, beta-, and gamma-ENaC subunits were all upregulated by
      dexamethasone (100 nM) in HMEECs. Dexamethasone treatment also increased the
      transcript expression of serum/glucocorticoid-regulated kinase1 (SGK1) and neural
      precursor cell-expressed developmentally downregulated (Nedd) 4-2, and decreased
      the transcript expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1). ENaC transcript expression was not changed after mifepristone (a
      glucocorticoid antagonist, 100 nM) + dexamethasone treatment when compared to the
      control, but increased after spironolactone (a mineralocorticoid antagonist, 100
      nM) + dexamethasone treatment. CONCLUSIONS: These findings indicate that
      dexamethasone increases the transcript and protein expression of the alpha-, beta
      , and gamma-ENaC subunits via the GR-SGK1-Nedd4-2 pathway and provides insight
      into the molecular mechanism of the increased sodium transport mediated by ENaC
      with steroid treatment in HMEECs. LEVEL OF EVIDENCE: N/A.

PMID- 24114933
TI  - Downregulation of Pgc-1alpha expression by tea leaves and their by-products.
AB  - Previous studies indicate that muscle Pgc-1alpha expression governs the
      proportion of muscle fibre types. As a first step in using diet to manipulate the
      proportion of muscle fibre types by using Pgc-1alpha expression, the present
      study investigates the modulation of Pgc-1alpha expression by feedstuffs. A
      luciferase-based Pgc-1alpha reporter construct (Pgc-1alpha(-2553)-luc) that
      contains the mouse Pgc-1alpha promoter (-2553 to +78 bp) was prepared. A screen
      of ethanol extracts from 33 feedstuffs indicated that oolong tea and roasted
      green tea extracts decreased Pgc-1alpha(-2553)-luc expression in C2C12 myoblasts.
      The transcriptional repression of Pgc-1alpha by tea leaf extracts was reproduced
      in hepatic HepG2 cells. We further examined the effects of the alcohol extracts
      of tea waste and its silage on Pgc-1alpha transcription; the tea waste silage
      extract inhibited Pgc-1alpha transcription. Treatment with the extracts of raw
      tea leaves, tea waste and tea waste silage effectively decreased Pgc-1alpha mRNA
      levels during myogenesis of myosatellite cells. The present results suggest that
      tea leaves and their by-products could be used to modulate proportions of muscle
      fibre types.

PMID- 24114936
TI  - Conversion between difluorocarbene and difluoromethylene ylide.
AB  - The interconversion between difluoromethylene ylide and difluorocarbene is
      described. The difluoromethylene ylide precursor, Ph3P(+)CF2CO2(-), could be
      turned into an efficient difluorocarbene reagent, whereas the classical
      difluorocarbene reagents, HCF2Cl and FSO2CF2CO2TMS, could generate highly
      reactive difluoromethylene ylide. Thus the Wittig difluoro-olefination and
      difluorocyclopropanation could be selectively realized by using the same reagent.
      In addition, the ylides obtained from different carbene sources showed different
      reactivity in Wittig reactions.

PMID- 24114935
TI  - Identifying multiple change points in a linear mixed effects model.
AB  - Although change-point analysis methods for longitudinal data have been developed,
      it is often of interest to detect multiple change points in longitudinal data. In
      this paper, we propose a linear mixed effects modeling framework for identifying
      multiple change points in longitudinal Gaussian data. Specifically, we develop a
      novel statistical and computational framework that integrates the expectation
      maximization and the dynamic programming algorithms. We conduct a comprehensive
      simulation study to demonstrate the performance of our method. We illustrate our
      method with an analysis of data from a trial evaluating a behavioral intervention
      for the control of type I diabetes in adolescents with HbA1c as the longitudinal
      response variable.

PMID- 24114934
TI  - Differences in the morphology of spinal V2a neurons reflect their recruitment
      order during swimming in larval zebrafish.
AB  - Networks of neurons in spinal cord generate locomotion. However, little is known
      about potential differences in network architecture that underlie the production
      of varying speeds of movement. In larval zebrafish, as swimming speed increases,
      Chx10-positive V2a excitatory premotor interneurons are activated from ventral to
      dorsal in a topographic pattern that parallels axial motoneuron recruitment.
      Here, we examined whether differences in the morphology and synaptic output of
      V2a neurons reflect their recruitment order during swimming. To do so, we used in
      vivo single-cell labeling approaches to quantify the dorsoventral distribution of
      V2a axonal projections and synapses. Two different classes of V2a neurons are
      described, cells with ascending and descending axons and cells that are only
      descending. Among the purely descending V2a cells, more dorsal cells project
      longer distances than ventral ones. Proximally, all V2a neurons have axonal
      distributions that suggest potential connections to cells at and below their own
      soma positions. At more distal locations, V2a axons project dorsally, which
      creates a cumulative intersegmental bias to dorsally located spinal neurons.
      Assessments of the synapse distribution of V2a cells, reported by synaptophysin
      expression, support the morphological observations and also demonstrate that
      dorsal V2a cells have higher synapse densities proximally. Our results suggest
      that V2a cells with more potential output to spinal neurons are systematically
      engaged during increases in swimming frequency. The findings help explain
      patterns of axial motoneuron recruitment and set up clear predictions for future
      physiological studies examining the nature of spinal excitatory network
      connectivity as it relates to movement intensity.

PMID- 24114937
TI  - Sonographic assessment of fetal secondary palate between 12 and 16 weeks of
      gestation using three-dimensional ultrasound.
AB  - OBJECTIVE: To evaluate fetal secondary palate in fetuses at 12 to 16 weeks'
      gestation by three-dimensional ultrasound. METHODS: Between June 2006 and July
      2008, volumes of palate were prospectively acquired in fetuses at gestational age
      of 12 to 16 weeks. Acquisition was performed when the fetus was facing the
      transducer with head extended at an angle of 30 degrees  to 40 degrees  to the
      ultrasound beam. Secondary palate was assessed off-line. RESULTS: Secondary
      palate was assessed in 45 fetuses with normal face anatomy and 4 fetuses with
      malformations of the face (one with retrognathia, one with retrognathia and
      micrognathia, one with cleft lip and one with cleft lip and primary palate). The
      secondary palate was visualized in 19/49 (38.7%) fetuses: in 2/49, only hard
      palate was demonstrated; in 6/49, only soft palate and in 11/49, both hard and
      soft palate were fully demonstrated. CONCLUSION: Information concerning evenness
      of secondary palate may be provided by three-dimensional ultrasound in 38.7% of
      examined fetuses at 12 to 16 weeks of gestation. This examination should be
      offered in pregnancies at high risk for cleft palate.

PMID- 24114940
TI  - What is the best test for pediatric gastroesophageal reflux disease?

PMID- 24114941
TI  - Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to
      suppress hepatocellular carcinoma vascular invasion by protein tyrosine
      phosphatase 1B recruitment.
AB  - Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor
      suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism
      has not yet been completely defined. Here, we employ a LECT2-affinity column plus
      liquid chromatography coupled with tandem mass spectrometry to identify LECT2
      binding proteins and found that MET receptor strongly interacted with LECT2
      protein. Despite the presence of hepatocyte growth factor, the LECT2 binding
      causes an antagonistic effect to MET receptor activation through recruitment of
      protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET
      activation also mainly contributes to the blockage of vascular invasion and
      metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed
      that the HxGxD motif is primarily responsible for MET receptor binding and its
      antagonistic effects. CONCLUSION: These findings reveal a novel, specific
      inhibitory function of LECT2 in HCC by the direct binding and inactivation of
      MET, opening a potential avenue for treating MET-related liver cancer.

PMID- 24114942
TI  - Comparison of bivalirudin versus heparin(s) during percutaneous coronary
      interventions in patients receiving prasugrel: a propensity-matched study.
AB  - BACKGROUND: Several percutaneous coronary intervention (PCI) trials have
      established that the use of bivalirudin (BIV) is associated with improved patient
      outcomes and substantial hospital cost savings, relative to heparin (HEP)-based
      regimens+/-glycoprotein IIb/IIIa inhibitors (GPIs). Whether these benefits
      persist with the use of prasugrel, a new third-generation oral thienopyridine,
      has not been previously evaluated. METHODS: Using the Premier hospital database,
      6986 patients treated with prasugrel who underwent elective, urgent, or primary
      PCI between quarter 3, 2009 and quarter 4, 2010 from 166 US hospitals were
      identified. These patients received either BIV (n=3377) or HEP+/-GPI (n=3609) as
      procedural anticoagulation. Outcomes of interest included bleeding, transfusions,
      death, and hospital length of stay (LOS). To control for patient and hospital
      level characteristics, propensity score-matching (PSM) analyses were performed.
      RESULTS: Mortality, clinically apparent bleeding, clinically apparent bleeding
      requiring transfusion, any transfusions, and LOS were all lower in patients
      treated with BIV as compared with patients treated with HEP+/-GPI. After PSM, the
      rate of transfusion was significantly lower with BIV (odds ratio: 0.57, 95%
      confidence interval: 0.34-0.96), and the hospital LOS was significantly shorter
      in patients treated with BIV compared with those treated with HEP+/-GPI (0.9+/
      2.0 vs 1.2+/-2.3 days, P<0.0001). CONCLUSIONS: In patients undergoing PCI and
      treated with prasugrel, the use of BIV rather than HEP+/-GPI is associated with
      significantly lower transfusion rate and LOS. These results suggest that the
      previously documented safety and cost-effectiveness benefits of BIV remain
      applicable when prasugrel is used.

PMID- 24114943
TI  - Hypocalcemia after total laryngectomy: incidence and risk factors.
AB  - OBJECTIVES/HYPOTHESIS: Hypocalcemia is common in the initial period after total
      laryngectomy. The purpose of the present study was to study the incidence of and
      risk factors for postlaryngectomy hypocalcemia at our institution. STUDY DESIGN:
      Retrospective review of 65 consecutive total laryngectomies. METHODS: Clinical
      data and calcium levels for the first postoperative week were collected.
      Biochemical hypocalcemia was defined as any corrected calcium level of < 2.0
      mmol/l in the first postoperative week. Severe hypocalcemia was defined as a
      calcium of < 1.8 mmol/l, or symptoms of hypocalcemia. Risk factors for
      hypocalcemia were studied. RESULTS: Five cases were excluded due to concomitant
      abdominal surgery (3), preoperative hypocalcemia (1), and no postoperative
      calcium levels (1). A total of 43% of patients had postoperative biochemical
      hypocalcemia. On univariate analysis, bilateral neck dissection was significant
      for hypocalcemia (P = 0.02), with pT4 classification having borderline
      significance (P = 0.07). On multivariate analysis, bilateral neck dissection (P =
      0.02) and salvage surgery were significant (P = 0.03), with pT4 stage again
      having borderline significance (P = 0.05). Extent of thyroidectomy, extent of
      pharyngectomy, and preoperative tracheostomy were not significant. Fifteen
      patients (25%) had severe hypocalcemia. There were no significant risk factors
      for severe hypocalcemia identified. CONCLUSIONS: Hypocalcemia is common after
      total laryngectomy, particularly in the postradiotherapy setting and in patients
      undergoing bilateral neck dissection. Preservation of one thyroid lobe does not
      appear to significantly reduce the risk.

PMID- 24114944
TI  - Characterization of a nonribosomal peptide antibiotic solid dispersion
      formulation by process analytical technologies sensors.
AB  - The focus of present investigation was to characterize and evaluate the
      variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing
      crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently,
      determining their percentage composition by nondestructive method of process
      analytical technology (PAT) sensors. The SD were prepared by heat fusion method
      and characterized for physicochemical and spectral properties. Enhanced
      dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000
      was observed indicating that the drug was present as solution and dispersed form
      within the polymer. The SD formulations were homogenous as shown by near infrared
      (NIR) chemical imaging data. Principal component analysis (PCA) and partial least
      square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data
      to develop model for quantification of drug and carrier. PLS of both data showed
      correlation coefficient >0.9934 with good prediction capability as revealed by
      smaller value of root mean square and standard error. The model based on NIR and
      PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion,
      the drug dissolution from the SD increased by decreasing crystallinity of PEG
      6000, and the chemometric models showed usefulness of PAT sensor in estimating
      percentage of both VCM and PEG-600 simultaneously.

PMID- 24114945
TI  - Clinical and enterovirus findings associated with acute flaccid paralysis in the
      Republic of Korea during the recent decade.
AB  - Acute flaccid paralysis (AFP) is described as sudden onset of flaccid paralysis
      in one or more limbs in children caused by polioviruses (PVs). PV eradication is
      achieved through intensive immunization and AFP attentive surveillance, according
      to the World Health Organization. Since 1998, the Korea Centers for Disease
      Control and Prevention has conducted surveillance system. This is an overview of
      surveillance in the Republic of Korea during the 10-year period from 2002 to
      2011. The surveillance system for wild PV eradication was conducted through
      reporting and laboratory testing. Cell culture isolates were identified by
      neutralization tests using standard polyclonal antisera typing. The molecular
      methods were used for further characterization to improve specificity. For
      genotyping, semi-nested RT-PCR was used to amplify part of the viral protein 1
      gene. Patients below 5 years of age accounted for the largest proportion of
      cases, and a positive association between age and incidence was found. In the
      total 285 cases, Guillain-Barre syndrome was the major leading causes of AFP. Non
      polio enterovirus was detected in some AFP patients. EV71 was detected in 21
      cases and Coxsackievirus (C) A2, CA6, CA9, CB2, CB3, CB4, CB5, and Echovirus (E)
      25, E30, Sabin strain polio 2, polio 1 and 3 were also detected in some patients.
      The present study represents a comprehensive 10-year country-based survey of AFP
      in the Republic of Korea. This surveillance could provide better understanding of
      the epidemiologic pattern, and clinical manifestations associated with specific
      genotypes of AFP in the Republic of Korea.

PMID- 24114946
TI  - Vocal fold motion impairment in multiple system atrophy.
AB  - OBJECTIVES/HYPOTHESIS: Multiple system atrophy (MSA) is a degenerative neurologic
      disorder that can affect vocal fold mobility. Our aim was to further elucidate
      the impact of vocal fold motion impairment (VFMI) in MSA. STUDY DESIGN:
      Retrospective case series. METHODS: We undertook a retrospective review of all
      MSA patients reporting voice or respiratory symptoms from 1975 to 2010 at Mayo
      Clinic Rochester who also received otolaryngologic examination. RESULTS: Thirty
      eight MSA patients demonstrated VFMI. Median duration of vocal or respiratory
      symptoms prior to diagnosis of MSA was 12.0 months (range, 1-60 months). Stridor
      was present in 25 (68%) of patients. There was bilateral VFMI in 32 (82.4%) of
      the patients and isolated VFMI of the left true vocal fold (TVF) in six (17.6%)
      of the patients. No patients had isolated right VFMI. There was isolated
      unilateral or bilateral paresis in 21 (55.3%) of the patients and unilateral or
      bilateral complete paralysis in 15 (39.5%) of the patients. One patient presented
      with left TVF paralysis and right TVF paresis, whereas one other patient had
      findings of right TVF paralysis and left TVF paresis comprising the remaining
      5.2% of patients with VFMI. The median survival after diagnosis of VFMI was 51.6
      months. Unilateral or bilateral TVF paralysis was statistically associated with a
      decreased overall survival (P = .0384). The presence of stridor was not
      associated with adverse prognosis. CONCLUSIONS: The increasing severity of VFMI
      negatively impacts overall survival in patients with MSA. Therefore,
      otolaryngologic examination is warranted at the time of MSA diagnosis.

PMID- 24114947
TI  - Bidirectional chiral inversion of trantinterol enantiomers after separate doses
      to rats.
AB  - The chiral inversion and pharmacokinetics of two enantiomers of trantinterol, a
      new beta2 agonist, were studied in rats dosed (+)- or (-)-trantinterol
      separately. Plasma concentrations of (+)- and (-)-trantinterol were measured by
      chiral stationary phase liquid chromatography tandem mass spectroscopy (LC
      MS/MS). The apparent inversion ratio was calculated as the ratio of AUC0-t of (-)
      trantinterol or (+)-trantinterol inverted from their antipodes to the sum of the
      AUC0-t of (-)- and (+)-trantinterol. Following single intravenous administration,
      both given enantiomers declined in similar plasma concentrations, suggesting that
      the two enantiomers have approximately the same disposition kinetics by the route
      of intravenous administration. However, after single oral administration, plasma
      concentrations of uninverted (-)-trantinterol at many timepoints were
      significantly higher than those of uninverted (+)-trantinterol, suggesting that
      the two enantiomers undergo apparently different absorption or metabolism after
      oral administration. Significant bidirectional chiral inversion occurred after
      intravenous and oral administration of (+)- or (-)-trantinterol. After dosing
      with optically pure enantiomer, the concentration of the administered enantiomer
      predominated in vivo. The AUC0-36 of (+)-trantinterol after intravenous and oral
      dosing of (-)-trantinterol were 16.6 +/- 5.2 and 33.3 +/- 16%, respectively of
      those of total [(+) + (-)] trantinterol. The AUC0-36 of (-)-trantinterol after
      intravenous and oral dosing of (+)-trantinterol were 19.6 +/- 8.8 and 37.9 +/-
      4.5%, respectively, of those of total [(-) + (+)] trantinterol. After intravenous
      administration of (+)- and (-)-trantinterol the chiral inversion ratios of the
      two enantiomers were not significantly different and similar results were found
      for oral administration. The extent of chiral inversion after intravenous
      administration was apparently lower, indicating that the bidirectional chiral
      inversion was not only systemic but also presystemic.

PMID- 24114948
TI  - Phosphate functionalized graphene with tunable mechanical properties.
AB  - The synthesis of a covalently modified graphene oxide derivative with exceptional
      and tunable compressive strength is reported. Treatment of graphene oxide with
      triethyl phosphite in the presence of LiBr produces monolithic structures
      comprised of lithium phosphate oligomers tethered to graphene through covalent
      phosphonate linkages. Variation of the both phosphate content and associated
      cation produces materials of various compressive strengths and elasticity. 

PMID- 24114949
TI  - Luminescent cyanoruthenate(II)-diimine and cyanoruthenium(II)-diimine complexes.
AB  - To improve the emission and excited-state properties of luminescent
      cyanometalates, new classes of highly solvatochromic luminescent
      cyanoruthenium(II) and cyanoruthenate(II) complexes of the general formulae
      [Ru(PR3)2(CN)2(NN)] and K[Ru(PR3)(CN)3(NN)], respectively, were developed. These
      complexes could be readily synthesized through the ligand-substitution reaction
      of K2[Ru(CN)4(PR3)2] with a diimine ligand. The geometrical isomerism of these
      complexes was characterized by using various spectroscopic techniques. Their
      photophysical properties, solvatochromism, and electrochemistry have also been
      investigated. Our detailed study showed that many of these complexes exhibited
      extremely environmentally sensitive emissions and significantly improved emission
      quantum efficiencies and lifetimes compared with the well-studied
      tetracyanoruthenate systems.

PMID- 24114950
TI  - Characterization of cross-linked gelatin nanoparticles by electrophoretic
      techniques in the liquid and the gas phase.
AB  - Biodegradable nanoparticles (NPs) and hence e.g. NPs prepared from glutaraldehyde
      crosslinked gelatin (gelatin NPs) are lately receiving increased attention in
      various fields like pharmaceutical technology and nutraceutics as biocompatible
      carriers for hardly water soluble drugs, molecules intended for sustained release
      or targeted transport. However, in vivo application of such materials requires a
      thoroughly characterization of corresponding particles. In a previous manuscript
      we demonstrated the applicability of chip electrophoresis for the separation of
      gelatin NPs from NP building blocks. Following our previous results we
      intensified our efforts in the characterization of gelatin NPs by electrophoresis
      in the liquid (capillary and chip format) and the gas phase (gas phase
      electrophoretic mobility molecular analysis, GEMMA). In doing so, we demonstrated
      differences between nominally comparable (from the concentration of initially
      employed material for crosslinking) gelatin NP preparation batches concerning (i)
      the amount of obtained NPs, (ii) the degree of NP crosslinking, (iii) the amount
      of NP building blocks present within samples and (iv) the electrophoretic
      mobility diameter of NPs. Differences were even more pronounced when NP
      preparations from batches with different content of initially employed gelatin
      were compared. Additionally, we compared three setups for the removal of low
      molecular weight components from samples after fluorescence labeling of NPs. In
      overall, the combination of the three employed analytical methods for gelatin NP
      characterization - CE in the capillary and the chip format as well as GEMMA -
      allows a more thoroughly characterization of NP containing samples.

PMID- 24114951
TI  - Comparative analysis of the dendritic organization of principal neurons in the
      lateral and central nuclei of the rhesus macaque and rat amygdala.
AB  - The amygdala plays a critical role in emotional processing and has been
      implicated in the etiology of numerous psychiatric disorders. It is an
      evolutionarily ancient structure that is enlarged in primates relative to
      rodents. Certain amygdala nuclei, such as the lateral nucleus, show relatively
      greater phylogenetic expansion than other nuclei. However, it is unknown whether
      there is also differential alteration in neuronal features. To address this
      question, we examined the dendritic arbors of principal neurons, visualized by
      using the Golgi method, in the lateral and central nuclei of young adult rhesus
      macaques and rats. Total dendritic length is greater in the macaque than in the
      rat. Dendritic trees are increased by 250% in length in the lateral nucleus of
      the monkey compared with the rat (6,009 MUm vs. 2,473 MUm); dendritic tree length
      in the central nucleus is increased by 50% (1,786 MUm vs. 1,232 MUm). Somal
      volume is increased 62% between species in the lateral nucleus and 48% in the
      central nucleus. Spine density is lower on macaque lateral nucleus dendrites
      compared with rat (-22%) but equivalent in the central nucleus. Spines are
      equally long in the lateral nucleus of rat and macaque, but spines are longer by
      about 20% in the central nucleus of the macaque. The alterations in dendritic
      structure that we observed between the two species suggest differences in the
      number and spacing of inputs into these nuclei that undoubtedly influence
      amygdala function.

PMID- 24114952
TI  - Impact of specific executive functions on driving performance in people with
      Parkinson's disease.
AB  - Executive functions encompass various cognitive processes and are critical in
      novel or demanding driving situations. Our aim was to determine the role of
      impairments in specific executive functions (updating, flexibility, inhibition)
      on road performance in drivers with Parkinson's disease (PD), a condition
      commonly associated with early executive dysfunction. In this pilot study, 19
      patients with mild to moderate PD and 21 healthy controls matched for age,
      education, and driving experience were tested using a neuropsychological battery
      assessing global cognitive abilities, updating (n-back task), flexibility (plus
      minus task), and inhibition (Stroop test). Participants also underwent a 45
      minute road test in which they were scored by a driving instructor and a second
      experimenter. To separate "at-risk" drivers from safe drivers, a composite
      driving indicator was calculated from the Test Ride for Investigating Practical
      Fitness to Drive score, the penalty score from the observation grid, and the
      number of safety interventions made by the driving instructor. Eight of the 40
      drivers (all PD) were rated as "at risk." Measures of updating (the n-back task)
      and mental flexibility (the plus-minus task) predicted driving safety even after
      adjustment for group status, explaining 53% of the total variance. These 2 tests
      also discriminated between safe and "at-risk" drivers within the PD group. These
      findings, although preliminary, suggest that updating and mental flexibility are
      critical for safe driving in PD. Assessment batteries for driving fitness should
      probe different aspects of executive functions, specifically when evaluating
      drivers with PD.

PMID- 24114953
TI  - A copper(I)-catalyzed three-component domino process: assembly of complex 1,2,3
      triazolyl-5-phosphonates from azides, alkynes, and H-phosphates.
AB  - Three is better than one! A new copper-catalyzed tricomponent reaction of a
      terminal alkyne, organic azide, and H-phosphate (CuAA[P]C) leads to a
      structurally diverse polysubstituted 1,2,3-triazolyl-5-phosphonate, which
      provides an efficient tool for the direct introduction of phosphonic acid groups
      by a "click reaction". 

PMID- 24114955
TI  - Neuropathic pain in children.
AB  - Neuropathic pain (NP), due to a lesion or disease of the somatosensory nervous
      system, is not well documented or researched in children. NP is a clinical
      diagnosis that can be difficult, especially in younger children. Nevertheless, it
      is important to recognise NP, as pain mechanisms and consequently management and
      prognosis differ from other types of long-term pain. NP is common in adult pain
      clinics but many of the underlying disease states in which it occurs are
      infrequently or never encountered in paediatric practice. However, NP in
      childhood has been reported, even in the very young in certain clinical
      situations. Causes of NP include traumatic injury, complex regional pain syndrome
      type II, cancer and chemotherapy, chronic infection, neurological and metabolic
      disease, and inherited sensory nerve dysfunction. The clinical and laboratory
      study of traumatic peripheral nerve injury has revealed important age-related
      differences in clinical presentation and prognosis. It is clear that mechanisms
      operating during development can profoundly modify the consequences of nerve
      damage and NP. Clinically, diagnosis, assessment and treatment of NP are based on
      methods and evidence derived from data in adults. Improvements in the
      understanding and management of NP are likely to come from developmentally
      appropriate improvements in the clarity and consistency of diagnosis and
      systematic, well-researched approaches to treatment. 

PMID- 24114956
TI  - First trimester maternal serum placental growth factor levels in twin
      pregnancies.
AB  - BACKGROUND: An understanding of the normal behavior of biochemical markers in
      twin pregnancies is necessary in order to offer prenatal screening to this
      subgroup. This study investigates the levels of first trimester maternal serum
      placental growth factor (PlGF) in twin and singleton pregnancies. METHODS: The
      PlGF concentrations were measured by an automated assay in the first trimester
      maternal serum of 440 dichorionic twin, 116 monochorionic twin, and 607 singleton
      pregnancy samples thawed from frozen storage. RESULTS: The PlGF concentrations in
      singleton levels were predicted by gestational age, maternal ethnicity, and
      smoking status. Following the correction for these variables, PlGF levels were,
      on average, 41% higher in dichorionics, but only 16% higher in monochorionics,
      compared to singleton pregnancies. CONCLUSIONS: First trimester maternal serum
      PlGF levels are increased in twin pregnancies compared with singleton
      pregnancies, but to less of an extent than is common with other screening
      markers, especially in monochorionic twins.

PMID- 24114957
TI  - Phase I design for completely or partially ordered treatment schedules.
AB  - The majority of methods for the design of phase I trials in oncology are based
      upon a single course of therapy, yet in actual practice, it may be the case that
      there is more than one treatment schedule for any given dose. Therefore, the
      probability of observing a dose-limiting toxicity may depend upon both the total
      amount of the dose given, as well as the frequency with which it is administered.
      The objective of the study then becomes to find an acceptable combination of both
      dose and schedule. Past literature on designing these trials has entailed the
      assumption that toxicity increases monotonically with both dose and schedule. In
      this article, we relax this assumption for schedules and present a dose-schedule
      finding design that can be generalized to situations in which we know the
      ordering between all schedules and those in which we do not. We present
      simulation results that compare our method with other suggested dose-schedule
      finding methodology.

PMID- 24114958
TI  - Contrasting effects of Kruppel-like factor 4 on X-ray-induced double-strand and
      single-strand DNA breaks in mouse astrocytes.
AB  - Astrocytes, the most common cell type in the brain, play a principal role in the
      repair of damaged brain tissues during external radiotherapy of brain tumours. As
      a downstream gene of p53, the effects of Kruppel-like factor 4 (KLF4) in response
      to X-ray-induced DNA damage in astrocytes are unclear. In the present study, KLF4
      expression was upregulated after the exposure of astrocytes isolated from the
      murine brain. Inhibition of KLF4 expression using lentiviral transduction
      produced less double-strand DNA breaks (DSB) determined by a neutral comet assay
      and flow cytometric analysis of phosphorylated histone family 2A variant and more
      single-strand DNA breaks (SSB) determined by a basic comet assay when the
      astrocytes were exposed to 4 Gy of X-ray radiation. These data suggest that
      radiation exposure of the tissues around brain tumour during radiation therapy
      causes KLF4 overexpression in astrocytes, which induces more DSB and reduces SSB.
      This causes the adverse effects of radiation therapy in the treatment of brain
      tumours.

PMID- 24114959
TI  - Synthesis and biological evaluation of novel 4-(2-fluorophenoxy)-2-(1H-tetrazol-1
      yl)pyridines bearing semicarbazone moieties as potent antitumor agents.
AB  - A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing
      semicarbazone moieties were synthesized and evaluated for their in vitro
      antitumor potency. Some of the compounds (10b, 10c, 10e-10h, 10m-10p, 10r, and
      11b) exhibited moderate to excellent antitumor activity as compared to sorafenib
      and PAC-1, as well as low levels of toxicity toward the human fetal lung
      fibroblast cell line WI-38. The most promising compound 10p (IC50 = 0.08, 0.36,
      0.97 uM) was 45.1-, 6.1-, and 2.4-fold more active than sorafenib (IC50 = 3.61,
      2.19, 2.32 uM), and 17, 3.2, and 2.9 times better than PAC-1 (IC50 = 1.36, 1.17,
      2.83 uM) against three cancer cell lines (HT-29, H460, and MKN-45), respectively.
      In addition, further studies examining enzymatic activity suggested that the
      marked pharmacological activity observed might be ascribed to an inhibitory
      action against CRAf kinase.

PMID- 24114960
TI  - Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and
      observational data.
AB  - The 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society
      (ATS) guidelines proposed "minor" criteria to predict intensive care unit (ICU)
      admission in patients with community-acquired pneumonia. These criteria were
      based on expert opinion. Consequently, the authors of the guidelines asked
      investigators to determine whether the score could be simplified by excluding
      noncontributory variables. Each IDSA/ATS minor criterion was validated using a
      random effects meta-analysis of seven studies. Variables present in <5% of cases
      or that were nonsignificantly associated with mortality/ICU admission were
      excluded. A simplified score excluding these variables was tested for prediction
      of mortality and ICU admission in an established database. Prediction was
      assessed using the area under the receiver operator characteristic curve (AUC).
      Leukopenia (<4000 cells.mm(-3)), thrombocytopenia (<100,000 cells.mm(-3)) and
      hypothermia <36 degrees C occurred in <5% of cases. A simplified score excluding
      these variables was performed similarly for prediction of mortality, AUC 0.77
      (95% CI 0.73-0.81) versus 0.78 (95% CI 0.74-0.82) (p=0.9) and intensive care unit
      admission, AUC 0.85 (95% CI 0.82-0.87) versus 0.85 (95% CI 0.82-0.88) (p=0.9).
      Additional predictors suggested by the IDSA/ATS were associated with mortality
      and ICU admission, but only incorporating acidosis (pH <7.35) altered the AUC
      (0.82 (95% CI 0.78-0.86) (p=0.6) for mortality and 0.86 (95% CI 0.82-0.88)
      (p=0.8) for ICU admission). No improvements were statistically significant. The
      IDSA/ATS criteria can be simplified by removing three infrequent variables.

PMID- 24114961
TI  - Rapidly progressing tuberculosis outbreak in a very low risk group.

PMID- 24114962
TI  - COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Mexican women.
AB  - We hypothesised that biomass smoke exposure is associated with an airway
      predominant chronic obstructive pulmonary disease (COPD) phenotype, while tobacco
      related COPD is associated with an emphysema-predominant phenotype. In this cross
      sectional study, female never-smokers with COPD and biomass exposure (n=21) and
      female ex-cigarette smokers with COPD without biomass exposure (n=22) completed
      computed tomography (CT) at inspiration and expiration, pulmonary function, blood
      gas, exercise tolerance, and quality of life measures. Two radiologists scored
      the extent of emphysema and air trapping on CT. Quantitative emphysema severity
      and distribution and airway wall thickness were calculated using specialised
      software. Women in the tobacco group had significantly more emphysema than the
      biomass group (radiologist score 2.3 versus 0.7, p=0.001; emphysema on CT 27%
      versus 19%, p=0.046; and a larger size of emphysematous spaces, p=0.006). Women
      in the biomass group had significantly more air trapping than the tobacco group
      (radiologist score 2.6 and 1.5, respectively; p=0.02) and also scored lower on
      the symptom, activities and confidence domains of the quality of life assessment
      and had lower oxygen saturation at rest and during exercise (p<0.05). Biomass
      smoke exposure is associated with less emphysema but more air trapping than
      tobacco smoke exposure, suggesting an airway-predominant phenotype. 

PMID- 24114963
TI  - Helicobacter pylori seroprevalence in patients with idiopathic pulmonary
      fibrosis.

PMID- 24114965
TI  - Impact of symptoms of anxiety and depression on COPD Assessment Test scores.

PMID- 24114964
TI  - Second-line therapy in elderly patients with advanced nonsmall cell lung cancer.
AB  - There is no dedicated study on second-line treatment for elderly patients with
      advanced nonsmall cell lung cancer (NSCLC). We report the results on second-line
      erlotinib therapy from our previously published phase III study comparing single
      agent therapy with platinum-based doublet (carboplatin plus paclitaxel) therapy
      in 451 elderly patients. Erlotinib was given to patients exhibiting disease
      progression or experiencing excessive toxicity during first-line therapy, until
      further progression or unacceptable toxicity. In total, 292 (64.7%) patients
      received erlotinib as second-line therapy. Initial performance status 0-1, stage
      IV NSCLC and an Activities of Daily Living score of 6 were independent factors
      for receiving erlotinib. Median (95% CI) overall survival was 4 (3.2-6.7) versus
      6.8 (5.0-8.3) months in the single-agent and doublet arms, respectively
      (p=0.089). Performance status 0-1, never having smoked, adenocarcinoma and weight
      loss <=5% were favourable independent prognostic factors of survival, whereas the
      randomisation arm had no significant impact. Among the 292 patients who received
      erlotinib, 60 (20.5%) experienced grade 3-4 toxic effects, the most frequent
      being rash. Erlotinib as second-line therapy is feasible, leading to efficacy
      results similar to those obtained in a previous randomised study that was not
      dedicated to elderly patients, with acceptable toxicity.

PMID- 24114966
TI  - Tuberculosis transmission between foreign- and native-born populations in the
      EU/EEA: a systematic review.
AB  - Tuberculosis (TB) control programmes of many low TB incidence countries of the
      European Union/European Economic Area (EU/EEA) perceive challenges in controlling
      TB due to high numbers of TB in migrants from high-incidence countries. To assess
      the extent of TB transmission from the foreign-born to the native-born
      population, we quantitatively investigated the dynamics of TB transmission
      between these populations in the EU/EEA, using published molecular
      epidemiological studies. We searched PubMed and EMBASE databases from 1990 to
      August 2012. We identified 15 studies performed during 1992-2007 covering 12,366
      cases, of which median (range) 49.2% (17.7%-86.4%) were foreign-born. The
      proportion of clustered isolates ranged between 8.5% and 49.1% of the total
      number of TB cases genotyped and among these, foreign-born cases were equally or
      more likely to have unique isolates compared to native-born cases. One third of
      the clusters were "mixed", i.e. composed of foreign- and native-born cases,
      involving 0-34.2% of all genotyped cases. Cross-transmission among foreign and
      native populations was bidirectional, with wide differences across studies. This
      systematic review provides evidence that TB in a foreign-born population does not
      have a significant influence on TB in the native population in EU/EEA.

PMID- 24114967
TI  - Neutrophilia independently predicts death in tuberculosis.

PMID- 24114968
TI  - Obesity in COPD: the effect of water-based exercise.

PMID- 24114969
TI  - A comparison of the efficacy and safety of once-daily fluticasone
      furoate/vilanterol with twice-daily fluticasone propionate/salmeterol in moderate
      to very severe COPD.
AB  - Fluticasone furoate/vilanterol trifenatate (FF/VI) is a once-daily inhaled
      corticosteroid/long-acting beta2-agonist combination in development for chronic
      obstructive pulmonary disease (COPD) treatment. We compared the efficacy and
      safety of FF/VI versus fluticasone propionate/salmeterol (FP/SAL) twice daily
      over 12 weeks. Moderate to very severe COPD patients received FF/VI 100/25 MUg
      once daily in the morning (n=266) or FP/SAL 500/50 MUg twice daily (n=262). The
      primary end-point was a change from baseline in 0-24 h weighted mean forced
      expiratory volume in 1 s (wmFEV1) at 12 weeks. Additional end-points included
      time to 100 mL improvement from baseline on day 1 and a change from baseline in
      St George's Respiratory Questionnaire (SGRQ). Safety was also assessed. wmFEV1
      (mean 130 mL) was greater and time to 100 mL improvement shorter (median 16 min)
      with FF/VI than FP/SAL (weighted mean 108 mL, median 28 min). Health status (SGRQ
      total score) improved in both groups (FF/VI -4.3 units, FP/SAL -3.0 units).
      Differences between treatments were not statistically significant. Six patients
      in the FF/VI (2%) and three in the FP/SAL (1%) arm experienced serious adverse
      events, none of which were considered to be drug related. Improvements in lung
      function and health status were not significantly different between FF/VI 100/25
      MUg once daily and FP/SAL 500/50 MUg twice daily; there was no apparent
      difference between the safety profiles of either therapy.

PMID- 24114970
TI  - Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease
      progression and predicts outcome in hepatocellular carcinoma patients.
AB  - Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related
      death. Despite the advances in diagnosis and management of HCC, the biology of
      this tumor remains poorly understood. Recent evidence highlighted long noncoding
      RNAs (lncRNAs) as crucial determinants of HCC development. In this study we
      report the lncRNA HOXA transcript at the distal tip (HOTTIP) as significantly up
      regulated in HCC specimens. The HOTTIP gene is located in physical contiguity
      with HOXA13 and directly controls the HOXA locus gene expression by way of
      interaction with the WDR5/MLL complex. HOX genes encode transcription factors
      regulating embryonic development and cell fate. We previously described HOX genes
      deregulation to be involved in hepatocarcinogenesis. Indeed, we observed the
      marked up-regulation of HOXA13 in HCC. Here, by correlating clinicopathological
      and expression data, we demonstrate that the levels of HOTTIP and HOXA13 are
      associated with HCC patients' clinical progression and predict disease outcome.
      In contrast to the majority of similar studies, our data were obtained from snap
      frozen needle HCC biopsies (n=52) matched with their nonneoplastic counterparts
      collected from patients who had not yet received any HCC-tailored therapeutic
      treatments at the time of biopsy. In addition, taking advantage of gain and loss
      of function experiments in liver cancer-derived cell lines (HuH-6 and HuH-7), we
      uncover a novel bidirectional regulatory loop between HOTTIP/HOXA13. CONCLUSION:
      Our study highlights the key role of HOTTIP and HOXA13 in HCC development by
      associating their expression with metastasis and survival in HCC patients,
      provides novel insights on the function of lncRNA-driven hepatocarcinogenesis,
      and paves the way for further investigation about the possible role of HOTTIP as
      a predictive biomarker of HCC.

PMID- 24114971
TI  - Adiponectin levels are elevated in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: In addition to insulin-sensitizing effects, adiponectin influences
      several mechanisms involved in pulmonary arterial hypertension (PAH)
      pathobiology. Insulin resistance has been associated with PAH, and elevated
      adiponectin levels have been described in left heart failure (HF) as a response
      to the increased metabolic stress. No studies have been performed in right HF or
      PAH patients. HYPOTHESIS: Compared to healthy controls, PAH patients have a
      different plasma adipocytokine profile, higher insulin resistance, and higher
      inflammatory systemic activation. METHODS: A case-control study was conducted in
      PAH patients individually matched for sex, age, and body mass index. We
      characterized the clinical features, functional status (6-minute walking test),
      and hemodynamic profile of cases (n=25). We measured insulin resistance
      (homeostasis model assessment and high-density lipoprotein/triglycerides ratio),
      inflammatory systemic activation (high-sensitivity C-reactive protein), and
      plasma adipocytokine profile (adiponectin, leptin, visfatin, and resistin) in
      cases and controls. RESULTS: PAH patients had significantly higher adiponectin
      levels than controls (12.4+/-6.9 vs 8.1+/-4.5 ug/mL; P<0.05) and higher high
      sensitivity C-reactive protein (2.96+/-3.2 vs 1.08+/-1.1; P<0.05). No
      statistically significant differences were found in plasma levels of leptin,
      visfatin, and resistin between groups. CONCLUSIONS: Adiponectin levels are
      increased in PAH patients compared to controls. Further studies are needed to
      study the potential role of adiponectin as a PAH biomarker.

PMID- 24114972
TI  - Cervical cancer screening by cytology and human papillomavirus testing during
      pregnancy in French women with poor adhesion to regular cervical screening.
AB  - In France, cervical screening is opportunistic and approximately 40% of women do
      not attend regular screening programs. The aim of this study was (1) to assess
      the prevalence of human papillomavirus (HPV) cervical infection and of
      cytological abnormalities in a population of young pregnant women with poor
      adherence to cervical cancer screening and (2) to evaluate the adherence to a
      screening strategy combining HPV testing and cytology during pregnancy. For this
      purpose, pregnant women benefited from a cervical smear associated with HPV DNA
      detection. High-risk HPV types were detected and identified using the HC2 assay
      and the INNO-LiPA HPV genotyping Extra assay. Two hundred forty-seven women (mean
      age 26.6 +/- 5.1 years) were enrolled. Among them, 76.8% did not attend regular
      cervical cancer screening programs. High-risk HPV types were detected in 50
      (20.2%) samples, HPV 16 being the most frequent (N = 12; 14.5%), with multiple
      HPV infection in 17 samples (27%). Nine (3.6%) abnormal cervical smears were
      diagnosed. Follow-up of women with abnormal cytology and/or infection with high
      risk HPV was obtained in 29 cases (55.8%), showing 12 persistent high-risk HPV
      infections. Nine women had colposcopy with a final diagnosis of four normal
      cervixes, three cervical intraepithelial neoplasia grade 1 and two cervical
      intraepithelial neoplasia grade 2. Overall, women adherence to the free post
      partum follow-up visit was 53.5%. This study suggests that a screening program
      combining HPV testing with cervical cytology during pregnancy may be one option
      to target young women with poor adhesion to regular cervical cancer screening.

PMID- 24114973
TI  - In response to Intratympanic dexamethasone injection for refractory tinnitus:
      prospective placebo-controlled study.

PMID- 24114975
TI  - Multiply nitrated high-energy dense oxidizers derived from the simple amino acid
      glycine.
AB  - Various energetic polynitro esters, carbamates, and nitrocarbamates that were
      derived from the amino acid glycine were fully characterized by single-crystal X
      ray diffraction, vibrational spectroscopy (IR and Raman), multinuclear NMR
      spectroscopy, elemental analysis, and differential scanning calorimetry (DSC).
      Owing to their positive oxygen balance, the suitability of these compounds as
      potential oxidizers in energetic formulations was investigated and discussed. In
      addition, the heats of formation of the products were calculated by using the
      Gaussian 09 program package at the CBS-4M level of theory. From these values and
      the calculated densities (from the X-ray data), several detonation parameters,
      such as detonation pressure, velocity, energy, and temperature, were computed by
      using the EXPLO5 code. Furthermore, their sensitivities towards impact, friction,
      and electrostatic discharge were tested by using a drop hammer, a friction tester
      (both BAM certified), and a small-scale electrical-discharge device,
      respectively. 

PMID- 24114974
TI  - Early postnatal expression and localization of matrix metalloproteinases-2 and -9
      during establishment of rat hippocampal synaptic circuitry.
AB  - Matrix metalloproteinases (MMPs) are extracellular proteolytic enzymes that
      contribute to pericellular remodeling in a variety of tissues, including brain,
      where they function in adult hippocampal synaptic structural and functional
      plasticity. Synaptic plasticity and remodeling are also important for development
      of connectivity, but it is unclear whether MMPs--particularly MMP-2 and -9, the
      major MMPs operative in brain--contribute at these stages. Here, we use a
      combination of biochemical and anatomical methods to characterize expression and
      localization of MMP-2 and MMP-9 in early postnatal and adult rat hippocampus.
      Gene and protein expression of these MMPs were evident throughout hippocampus at
      all ages examined, but expression levels were highest during the first postnatal
      week. MMP-2 and MMP-9 immunolocalized to punctate structures within the neuropil
      that codistributed with foci of proteolytic activity, as well as with markers of
      growing axons and synapses. Taken together, discrete foci of MMP proteolysis are
      likely important for actively shaping and remodeling cellular and connectional
      architecture as hippocampal circuitry is becoming established during early
      postnatal life.

PMID- 24114976
TI  - Genetic algorithm guided population pharmacokinetic model development for
      simvastatin, concurrently or non-concurrently co-administered with amlodipine.
AB  - An automated model development was performed for simvastatin, co-administered
      with amlodipine concurrently or non-concurrently (i.e., 4 hours later) in 17
      patients with coexisting hyperlipidemia and hypertension. The single objective
      hybrid genetic algorithm (SOHGA) was implemented in the NONMEM software by
      defining the search space for structural, statistical and covariate models.
      Candidate models obtained from the SOHGA runs were further assessed for
      biological plausibility and the precision of parameter estimates, followed by
      traditional backward elimination process for model refinement. The final
      population pharmacokinetic model shows that the elimination rate constant for
      simvastatin acid, the active form by hydrolysis of its lactone prodrug (i.e.,
      simvastatin), is only 44% in the concurrent amlodipine administration group
      compared with the non-concurrent group. The application of SOHGA for automated
      model selection, combined with traditional model selection strategies, appears to
      save time for model development, which also can generate new hypotheses that are
      biologically more plausible.

PMID- 24114977
TI  - Should patients with posterior nasal packing require ICU admission?

PMID- 24114978
TI  - Significance of the natural occurrence of L- versus D-pipecolic acid: a review.
AB  - Pipecolic acid naturally occurs in microorganisms, plants, and animals, where it
      plays many roles, including the interactions between these organisms, and is a
      key constituent of many natural and synthetic bioactive molecules. This article
      provides a review of current knowledge on the natural occurrence of pipecolic
      acid and the known and potential significance of its L- and D-enantiomers in
      different scientific disciplines. Knowledge gaps with perspectives for future
      research identified within this article include the roles of the L- versus the D
      enantiomer of pipecolic acid in plant resistance, nutrient acquisition, and
      decontamination of polluted soils, as well as rhizosphere ecology and medical
      issues.

PMID- 24114979
TI  - Microchip electrophoresis at elevated temperatures and high separation field
      strengths.
AB  - We report free-solution microchip electrophoresis performed at elevated
      temperatures and high separation field strengths. We used microfluidic devices
      with 11 cm long separation channels to conduct separations at temperatures
      between 22 (ambient) and 45 degrees C and field strengths from 100 to 1000 V/cm.
      To evaluate separation performance, N-glycans were used as a model system and
      labeled with 8-aminopyrene-1,3,6-trisulfonic acid to impart charge for
      electrophoresis and render them fluorescent. Typically, increased diffusivity at
      higher temperatures leads to increased axial dispersion and poor separation
      performance; however, we demonstrate that sufficiently high separation field
      strengths offset the impact of increased diffusivity in order to maintain
      separation efficiency. Efficiencies for these free-solution separations are the
      same at temperatures of 25, 35, and 45 degrees C with separation field strengths
      >= 500 V/cm. 

PMID- 24114980
TI  - Protein carbonylation: proteomics, specificity and relevance to aging.
AB  - Detection and quantification of protein carbonyls present in biological samples
      has become a popular, albeit indirect, method to determine the existence of
      oxidative stress. Moreover, the rise of proteomics has allowed the identification
      of the specific proteins targeted by protein carbonylation. This review discusses
      these methodologies and proteomic strategies and then focuses on the relationship
      between protein carbonylation and aging and the parameters that may explain the
      increased sensitivity of certain proteins to protein carbonylation.

PMID- 24114981
TI  - A 3D hybrid praseodymium-antimony-oxochloride compound: single-crystal-to-single
      crystal transformation and photocatalytic properties.
AB  - A 3D organic-inorganic hybrid compound, (2-MepyH)3[{Fe(1,10
      phen)3}3][{Pr4Sb12O18(OH)Cl(11.5)}(TDC)(4.5)({Pr4Sb12O18(OH)Cl(9.5)} Cl)].3(2
      Mepy).28H2O (1; 2-Mepy=2-methylpyridine, 1,10-phen=1,10-phenanthroline,
      H2TDC=thiophene-2,5-dicarboxylic acid), was hydrothermally synthesized and
      structurally characterized. Unusually, two kinds of high-nuclearity clusters,
      namely [(Pr4Sb12O18(OH)Cl11)(COO)5](5-) and [(Pr4Sb12O18(OH)Cl9)Cl(COO)5](4-),
      coexist in the structure of compound 1; two of the latter clusters are doubly
      bridged by two MU2-Cl(-) moieties to form a new centrosymmetric dimeric cluster.
      An unprecedented spontaneous and reversible single-crystal-to-single-crystal
      transformation was observed, which simultaneously involved a notable organic
      ligand movement between the metal ions and an alteration of the bridging ion in
      the dimeric cluster, induced by guest-release/re-adsorption, thereby giving rise
      to the interconversion between compound 1 and the compound (2-MepyH)3[{Fe(1,10
      phen)3}3][{Pr4Sb12O18(OH)Cl(11.5)}(TDC)4({Pr4Sb12O18Cl(10.5)(TDC)(0.5)(H2O)(1.5)}
      (0.5))].25H2O (1'). The mechanism of this transformation has also been discussed
      in great detail. Photocatalytic H2-evolution activity was observed for compound
      1' under UV light with Pt as a co-catalyst and MeOH as a sacrificial electron
      donor.

PMID- 24114982
TI  - Primary motor cortex long-term plasticity in multiple system atrophy.
AB  - In humans, intermittent and continuous theta-burst stimulation (iTBS and cTBS)
      elicit long-term changes in motor-evoked potentials (MEPs) reflecting long-term
      potentiation (LTP)- and depression (LTD)-like plasticity in the primary motor
      cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients
      with MSA. We also assessed whether responses to TBS reflect M1 excitability as
      tested by short-interval intracortical inhibition (SICI), intracortical
      facilitation (ICF), short-interval intracortical facilitation (SICF), and the
      input/output curves. We studied 20 patients with MSA and 20 healthy subjects
      (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy
      Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded
      from the right first dorsal interosseous muscle before TBS and 5, 15, and 30
      minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by
      SICI, ICF, SICF, and input/output curves, before TBS. Between-group analysis of
      variance showed that at all time points after iTBS MEPs increased, whereas after
      cTBS they decreased only in HS. In both subgroups tested, patients with
      predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs
      unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output
      curves. No correlation was found between patients' clinical features and
      responses to TBS and M1 excitability variables. These findings suggest impaired
      M1 plasticity in MSA.

PMID- 24114983
TI  - Endoscopic repair of an injured internal carotid artery utilizing femoral
      endovascular closure devices.
AB  - OBJECTIVES/HYPOTHESIS: Injury to the internal carotid artery is a feared
      complication of endoscopic endonasal surgery of the skull base. Such an event,
      although rare, is associated with high morbidity and mortality. Even if bleeding
      is controlled, permanent neurological defects frequently persist. Many techniques
      have been developed to manage internal carotid artery rupture with varying
      degrees of success. The purpose of this study was to explore endoscopic
      management of arterial damage with endovascular closure devices used for a
      femoral arteriotomy. The ability to remotely suture a damaged artery permits the
      possible adaptation of this technology in managing endoscopic arterial
      complications. STUDY DESIGN: Technical note. METHODS: After the creation of an
      endoscopic endonasal corridor in a cadaveric specimen, an arteriotomy was created
      at the cavernous portion of the internal carotid artery. The Angio-Seal,
      StarClose, and MynxGrip vascular closure devices were utilized under endoscopic
      guidance to repair the arteriotomy. Angiography was then done on a cadaver
      sutured with the StarClose. RESULTS: Both the Angio-Seal and StarClose were
      deployed quickly and appeared to provide sufficient closure of the arteriotomy.
      The Angio-Seal required the use of a guidewire and was longer to deploy when
      compared with the StarClose. The StarClose deployment was quick and facile. The
      MynxGrip also deployed without difficulty. CONCLUSIONS: The Angio-Seal and
      StarClose systems were both successfully deployed utilizing an endoscopic
      endonasal approach. The MynxGrip was the easiest to deploy and has the greatest
      potential to be of benefit in this application. Further studies with hemodynamic
      models are required to properly assess the appropriateness in this setting. LEVEL
      OF EVIDENCE: NA.

PMID- 24114984
TI  - What is the total number of protein molecules per cell volume? A call to rethink
      some published values.
AB  - Novel methods such as mass-spectrometry enable a view of the proteomes of cells
      in unprecedented detail. Recently, these efforts have culminated in quantitative
      measurements of the number of copies per cell for most expressed proteins in
      organisms ranging from bacteria to mammalian cells. Here, we estimate the
      expected total number of proteins per unit of cell volume using known parameters
      related to the composition of cells such as the fraction of cell mass that is
      protein, and the average protein length. Using simple arguments, we estimate a
      range of 2-4 million proteins per cubic micron (i.e. 1 fL) in bacteria, yeast,
      and mammalian cells. Interestingly, we find that measured values that are
      reported for fission yeast and mammalian cells are often about 3-10 times lower.
      We discuss this apparent discrepancy and how to use the estimate as benchmark to
      recalibrate proteome-wide quantitative censuses or to revisit assumptions about
      cell composition. 

PMID- 24114985
TI  - Verification bias in diagnostic accuracy studies for fine- and core needle biopsy
      of salivary gland lesions in otolaryngology journals: a systematic review and
      analysis.
AB  - BACKGROUND: Diagnostic test accuracy (DTA) studies for needle biopsy are
      frequently published in otolaryngology journals, but this body of literature has
      not been assessed for verification bias. METHODS: We conducted a systematic
      review of DTA studies on needle biopsy of salivary gland lesions appearing in
      otolaryngology journals. Studies were assessed by 2 reviewers for verification
      bias. RESULTS: We identified 95 DTA studies for needle biopsy of salivary gland
      lesions. Eighty-one studies (84%) had verification bias. Five of the biased
      studies provided sufficient data to estimate the extent of bias. Verification
      bias was associated with an overestimate of sensitivity and an underestimate of
      specificity. Studies on core needle biopsy (CNB) had a lower rate of verification
      bias than fine-needle aspiration (FNA) studies. CONCLUSION: Verification bias is
      common in DTA studies of needle biopsy for salivary gland lesions published in
      ear, nose, and throat (ENT) journals. Such studies overestimated sensitivity and
      underestimated specificity.

PMID- 24114986
TI  - Intra-operator and inter-operator reliability of manual and semiautomated
      measurement of fetal nuchal translucency: a cross sectional study.
AB  - OBJECTIVE: The goal of this study was to examine the intra-operator and inter
      operator differences of the manual and semiautomated nuchal translucency (NT)
      measurements and to evaluate if these differences alter women's risk status.
      METHODS: A cross sectional study was performed. Two operators obtained manual and
      semiautomated NT measurements of 153 NT images. The maximal acceptable difference
      in NT measurements within and between operators was 0.15 mm. Intra and inter
      operator differences were analyzed by the paired Student's t-test and homogeneity
      of variances by the Levene's test. Intra-operator and inter-operator agreement
      were quantified with Bland and Altman's limits of agreement, and changes in
      women's risk status were tested with the binomial test. RESULTS: Intra-operator
      agreement was high for each of the measurement methods. Operator 1 had lower SDS
      for manual measurements. Conversely, operator 2 had lower SDS of the differences
      for semiautomated measurements, although the SD never reached the same level as
      operator 1. Inter-operator agreement was highest for the semiautomated
      measurements. Changes in risk status occurred between the manual and inner-middle
      method resulting in different clinical policies in up to 1 out of 20 cases.
      CONCLUSION: Well-trained operators do not seem to benefit from the use of the
      semiautomated measurement methods.

PMID- 24114987
TI  - Synthesis of pyrimidones and evaluation of their xanthine oxidase inhibitory and
      antioxidant activities.
AB  - The increasing prevalence of gout has been accompanied by a growing number of
      patients intolerant to or with disease refractory to the available urate-lowering
      therapies. This metabolic disease is a common disease with a higher prevalence in
      men older than 30 years and in women older than 50 years. These findings
      highlight the need for emerging treatments to effectively lower urate levels. In
      this view, we describe the xanthine oxidase (XO) inhibitory activities of the
      synthesized compounds 5a-j and also their antioxidant activities. Compounds 5c,
      5d, 5f, 5h, and 5j exhibited good inhibitory activities against XO. On the other
      hand, compounds 5g and 5j exhibited moderate antioxidant activity. 

PMID- 24114988
TI  - Occupational fatality risks in the United States and the United Kingdom.
AB  - BACKGROUND: There are very few careful studies of differences in occupational
      fatality rates across countries, much less studies that try to account for those
      differences. METHODS: We compare the rate of work injury fatalities (excluding
      deaths due to highway motor vehicle crashes and those due to violence) identified
      by the US Census of Fatal Occupational Injuries in recent years with the number
      reported to the Health and Safety Executive in the United Kingdom (UK) and by
      other European Union (EU) members through Eurostat. RESULTS: In 2010, the
      fatality rate in the UK was about 1/3 the rate in the US. In construction the
      rate was about 1/4 the US rate, a difference that had grown substantially since
      the 1990s. Several other EU members had rates almost as low as the UK rate.
      Across EU countries, lower rates were associated with high-level management
      attention to safety issues and to in-house preparation of "risk assessments."
      CONCLUSIONS: Although work fatality rates have declined in the US, fatality rates
      are much lower and have declined faster in recent years in the UK. Efforts to
      find out the reasons for the much better UK outcomes could be productive.

PMID- 24114989
TI  - Health workforce in the United Arab Emirates: analytic point of view.
AB  - A strong health system is impossible without health workers who are the ultimate
      resource. Money and medical supplies are needed, but these inputs require an
      efficient workforce. Challenges with respect to human resources vary greatly
      between and within countries, and are associated with the political, economical,
      cultural and societal context of a country. Moreover, the gaps in the workforce
      do not generally relate to doctors but to nurses and other classes of health
      worker who make up the bulk of health workforce. The difficulties caused by low
      staff numbers are compounded by morale problems, skill imbalances and
      geographical maldistribution. This paper will discuss how it is difficult for the
      United Arab Emirates (UAE, a Middle East federation country) to wrestle
      effectively with the demands of a good health system, exploring how they lack the
      basis of health systems-motivated, trained and supported people. Additionally, we
      looked at how the UAE health system further challenged by negative work
      environment, and weak knowledge-base, out-migration and inadequate investment. At
      the end of our discussion, we are providing some suggestions to manage human
      resource problems in the UAE. Highlighting how a national workforce strategic
      plan is important to guide investments in human resources as the core component
      of strengthening the UAE national health system.

PMID- 24114990
TI  - Functional anatomy of the fiddler crab compound eye (Uca vomeris: Ocypodidae,
      Brachyura, Decapoda).
AB  - We describe the structural organization of the ommatidium in the compound eye of
      the fiddler crab, Uca vomeris, at both the light- and the electron-microscopy
      levels. We pay particular attention to the organization of the optical system,
      the retinular cells, the rhabdom, and of pigment cells. Although the fiddler crab
      compound eye is of the apposition type, typical for Brachyuran crabs, we identify
      a number of novel, functionally relevant aspects of ommatidial organization that
      have not previously been described. The flat corneal facet lenses provide the
      main focusing power and therefore must contain a gradient of refractive index.
      Each ommatidium has the typical set of eight retinular cells, with a distal
      retinular cell R8 lying close to the proximal tip of the crystalline cone. R8 is
      shaped into four lobes, which are separated by proximal extensions of the four
      crystalline cone cells and of distal extensions of retinular cells R1-R7. The
      microvilli in the R8 rhabdom are not aligned in a uniform direction, while the
      microvilli of the main rhabdom show the typical crustacean pattern of alternating
      bands of horizontally (R3, R4, R7) and vertically aligned microvilli (R1, R2, R5,
      R6). We describe in detail the distribution and structural properties of
      screening pigment granules in the two types of pigment cells and in the retinular
      cells in the equatorial eye. We discuss the functional significance of this fine
      structural organization of the fiddler crab compound eye in relation to visual
      processing and visual ecology.

PMID- 24114991
TI  - Clinical evaluation of a bioluminescent enzyme immunoassay for detecting
      norovirus in fecal specimens from patients with acute gastroenteritis.
AB  - Noroviruses (NoVs), which belong to the family Caliciviridae, are major causative
      agents of acute gastroenteritis worldwide. Thus, rapid and highly sensitive
      assays for detecting NoVs are required. Recently, a bioluminescent enzyme
      immunoassay (BLEIA) for detecting NoVs in fecal specimens was developed. This new
      assay was evaluated using fecal specimens obtained from acute gastroenteritis
      patients. Of the 107 specimens that were found to be NoV-positive by RT-PCR or RT
      LAMP, 104 specimens produced positive results in the BLEIA (sensitivity: 96.3%).
      On the other hand, no false-positive results were observed during the testing of
      176 NoV-negative specimens containing group A or C rotaviruses, astroviruses,
      sapoviruses, adenovirus type 41, bocaviruses, or parechoviruses. Furthermore, the
      BLEIA was able to detect many NoV genotypes in the tested specimens, including
      three genotypes from genogroup I (genotypes 1, 4, and 8) and ten genotypes
      belonging to genogroup II (genotypes 1, 2, 3, 4, 5, 6, 12, 13, 16, and 19). By
      quantifying the number of NoV genome copies in the clinical specimens tested with
      the BLEIA, its detection limit was estimated to be 10(6) genome copies per gram
      of stool and below. Furthermore, as the BLEIA can be performed with an automated
      device and does not involve complicated procedures it can be used to rapidly test
      many samples. Therefore, the BLEIA is a rapid and highly sensitive method and
      could be used as a diagnostic tool at hospitals and clinical laboratories that
      deal with large numbers of clinical specimens from acute gastroenteritis patients
      or food handlers. J. Med. Virol. 86:1219-1225, 2014. (c) 2013 Wiley Periodicals,
      Inc. 

PMID- 24114992
TI  - Association of rhinosinusitis with nasopharyngeal carcinoma: a population-based
      study.
AB  - OBJECTIVES/HYPOTHESIS: Although it is already known that the inflammation process
      elevates the risk of developing cancer, to date the association between
      rhinosinusitis and nasopharyngeal carcinoma (NPC) remains unknown. This study
      aimed to evaluate the association between rhinosinusitis and NPC based on a
      nationwide database. STUDY DESIGN: Case-control study. METHODS: In total, the
      cases comprised of 2,242 subjects with NPC and 6,726 randomly selected subjects
      as controls. Separate conditional logistic regression analyses were used to
      calculate the odds ratio (OR) for having been previously diagnosed with chronic
      and acute rhinosinusitis between the cases and controls. RESULTS: Of the total
      sample, 607 subjects (6.77%) had been diagnosed with chronic rhinosinusitis prior
      to the index date: 322 (14.36%) cases with NPC and 285 (4.24%) controls (P<.001).
      A conditional logistic regression analysis revealed that the OR of prior chronic
      rhinosinusitis for subjects with NPC is 3.83 (95% confidence interval [CI], 3.23
      4.53) as compared to controls after adjusting for the factors of income,
      urbanization, geographic location, tobacco use disorder, and alcohol
      abuse/dependence syndrome. Furthermore, 1,199 (53.48%) cases and 2,938 (42.19%)
      controls had been diagnosed with acute rhinosinusitis prior to the index date
      (P<.001).The adjusted OR of prior acute rhinosinusitis for subjects with NPC was
      1.57 (95% CI, 1.43-1.73) that of controls. CONCLUSIONS: This study detected an
      association between NPC and rhinosinusitis. We recommend that patients who are
      diagnosed with rhinosinusitis, either acute or chronic, seek out aggressive
      management to reduce the tissue burden and lower the risk of subsequently
      developing NPC. LEVEL OF EVIDENCE: 3b.

PMID- 24114994
TI  - Fullerene "superhalogen" radicals: the substituent effect on electronic
      properties of 1,7,11,24,27-C60X5.
AB  - Hexasubstituted fullerenes with the skew pentagonal pyramid (SPP) addition
      pattern are predominantly formed in many types of reactions and represent
      important and versatile building blocks for supramolecular chemistry, biomedical
      and optoelectronic applications. Regioselective synthesis and characterization of
      the new SPP derivative, C60(CF3)4(CN)H, in this work led to the experimental
      identification of the new family of "superhalogen fullerene radicals", species
      with the gas-phase electron affinity higher than that of the most electronegative
      halogens, F and Cl. Low-temperature photoelectron spectroscopy and DFT studies of
      different C60X5 radicals reveal a profound effect of X groups on their electron
      affinities (EA), which vary from 2.76 eV (X=CH3) to 4.47 eV (X=CN). The measured
      gas-phase EA of the newly synthesized C60(CF3)4CN equals 4.28(1) eV, which is
      about 1 eV higher than the EA of Cl atom. An observed remarkable stability of
      C60(CF3)4CN(-) in solution under ambient conditions opens new venues for design
      of air-stable molecular complexes and salts for supramolecular structures of
      electroactive functional materials.

PMID- 24114995
TI  - Mechanistic intricacies of gold-catalyzed intermolecular cycloadditions between
      allenamides and dienes.
AB  - The mechanism of the gold-catalyzed intermolecular cycloaddition between
      allenamides and 1,3-dienes has been explored by means of a combined experimental
      and computational approach. The formation of the major [4+2] cycloaddition
      products can be explained by invoking different pathways, the preferred ones
      being determined by the nature of the diene (electron neutral vs. electron rich)
      and the type of the gold catalyst (AuCl vs. [IPrAu](+), IPr=1,3-bis(2,6
      diisopropylphenyl)imidazole-2-ylidene). Therefore, in reactions catalyzed by
      AuCl, electron-neutral dienes favor a concerted [4+3] cycloaddition followed by a
      ring contraction event, whereas electron-rich dienes prefer a stepwise cationic
      pathway to give the same type of formal [4+2] products. On the other hand, the
      theoretical data suggest that by using a cationic gold catalyst, such as
      [IPrAuCl]/AgSbF6, the mechanism involves a direct [4+2] cycloaddition between the
      diene and the gold-activated allenamide. The theoretical data are also consistent
      with the observed regioselectivity as well as with the high selectivity towards
      the formation of the enamide products with a Z configuration. Finally, our data
      also explain the formation of the minor [2+2] products that are obtained in
      certain cases.

PMID- 24114993
TI  - Impact of mTORC1 inhibition on keratinocyte proliferation during skin tumor
      promotion in wild-type and BK5.AktWT mice.
AB  - In this study, we examined the impact of rapamycin on mTORC1 signaling during 12
      O-tetradecanoylphorbol-13-acetate (TPA)-induced keratinocyte proliferation and
      skin tumor promotion in both wild-type (FVB/N) and BK5.Akt(WT) mice. TPA
      activated mTORC1 signaling in a time-dependent manner in cultured primary mouse
      keratinocytes and a mouse keratinocyte cell line. Early activation (15-30 min) of
      mTORC1 signaling induced by TPA was mediated in part by PKC activation, whereas
      later activation (2-4 h) was mediated by activation of EGFR and Akt. BK5.Akt(WT)
      transgenic mice, where Akt1 is overexpressed in basal epidermis, are highly
      sensitive to TPA-induced epidermal proliferation and two-stage skin
      carcinogenesis. Targeting mTORC1 with rapamycin effectively inhibited TPA-induced
      epidermal hyperplasia and hyperproliferation as well as tumor promotion in a dose
      dependent manner in both wild-type and BK5.Akt(WT) mice. A significant expansion
      (~threefold) of the label retaining cell (LRC) population per hair follicle was
      observed in BK5.Akt(WT) mice compared to FVB/N mice. There was also a significant
      increase in K15 expressing cells in the hair follicle of transgenic mice that
      coincided with expression of phospho-Akt, phospho-S6K, and phospho-PRAS40,
      suggesting an important role of mTORC1 signaling in bulge-region keratinocyte
      stem cell (KSC) homeostasis. After 2 weeks of TPA treatment, LRCs had moved
      upward into the interfollicular epidermis from the bulge region of both wild-type
      and BK5.Akt(WT) mice. TPA-mediated LRC proliferation and migration was
      significantly inhibited by rapamycin. Collectively, the current data indicate
      that signaling through mTORC1 contributes significantly to the process of skin
      tumor promotion through effects on proliferation of the target cells for tumor
      development.

PMID- 24114997
TI  - The axial rearrangement mixer: working principles and in-depth investigation.
AB  - In the current paper, an axial rearrangement mixer is studied. The mixer aims to
      flatten out occasional composition fluctuations originating from the pump. In a
      first phase, dispersion in a single mixer channel is investigated using pulses
      introduced by a dedicated injection pulse generator. The mixing in the single
      channel is studied for different flow rates and a model is presented based on the
      experimental data. Next, the resulting signal for the whole mixer is studied. 

PMID- 24114996
TI  - Non-enzymatic glycation and glycoxidation protein products in foods and diseases:
      an interconnected, complex scenario fully open to innovative proteomic studies.
AB  - The Maillard reaction includes a complex network of processes affecting food and
      biopharmaceutical products; it also occurs in living organisms and has been
      strictly related to cell aging, to the pathogenesis of several (chronic)
      diseases, such as diabetes, uremia, cataract, liver cirrhosis and various
      neurodegenerative pathologies, as well as to peritoneal dialysis treatment.
      Dozens of compounds are involved in this process, among which a number of protein
      adducted derivatives that have been simplistically defined as early, intermediate
      and advanced glycation end-products. In the last decade, various bottom-up
      proteomic approaches have been successfully used for the identification of
      glycation/glycoxidation protein targets as well as for the characterization of
      the corresponding adducts, including assignment of the modified amino acids. This
      article provides an updated overview of the mass spectrometry-based procedures
      developed to this purpose, emphasizing their partial limits with respect to
      current proteomic approaches for the analysis of other post-translational
      modifications. These limitations are mainly related to the concomitant sheer
      diversity, chemical complexity, and variable abundance of the various derivatives
      to be characterized. Some challenges to scientists are finally proposed for
      future proteomic investigations to solve main drawbacks in this research field.

PMID- 24114998
TI  - Expression, functionality, and localization of apurinic/apyrimidinic
      endonucleases in replicative and non-replicative forms of Trypanosoma cruzi.
AB  - Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to
      overcome oxidative damage by ROS/RNS all along its life cycle to survive and to
      establish a chronic infection. We propose that T. cruzi is able to survive, among
      other mechanisms of detoxification, by repair of its damaged DNA through
      activation of the DNA base excision repair (BER) pathway. BER is highly conserved
      in eukaryotes with apurinic/apirimidinic endonucleases (APEs) playing a
      fundamental role. Previous results showed that T. cruzi exposed to hydrogen
      peroxide and peroxinitrite significantly decreases its viability when co
      incubated with methoxyamine, an AP endonuclease inhibitor. In this work the
      localization, expression and functionality of two T. cruzi APEs (TcAP1, Homo
      sapiens APE1 orthologous and TcAP2, orthologous to Homo sapiens APE2 and to
      Schizosaccaromyces pombe Apn2p) were determined. These enzymes are present and
      active in the two replicative parasite forms (epimastigotes and amastigotes) as
      well as in the non-replicative, infective trypomastigotes. TcAP1 and TcAP2 are
      located in the nucleus of epimastigotes and their expression is constitutive.
      Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are
      inhibited by methoxyamine. Overexpression of TcAP1 increases epimastigotes
      viability when they are exposed to acute ROS/RNS attack. This protective effect
      is more evident when parasites are submitted to persistent ROS/RNS exposition,
      mimicking nature conditions. Our results confirm that the BER pathway is involved
      in T. cruzi resistance to DNA oxidative damage and points to the participation of
      DNA AP endonucleases in parasite survival.

PMID- 24114999
TI  - Differences in perception of hearing handicap between cochlear implant users and
      their spouses.
AB  - OBJECTIVES/HYPOTHESIS: To examine the relationship between patient and proxy
      ratings of health-related quality of life (HRQL) in patients with cochlear
      implants. STUDY DESIGN: Prospective survey. METHODS: Eighty-two adult cochlear
      implant recipients and their spouses/partners were asked to complete the Nijmegen
      Cochlear Implant Questionnaire (NCIQ) and the Hearing Participation Scale (HPS)
      that were mailed to them. RESULTS: For the NCIQ, there were 38 useable responses
      from recipients and 31 useable responses from the partners. There were 27 paired
      and useable questionnaires (i.e., from both the recipient and his/her partner).
      For the HPS, there were 42 useable responses from recipients and 36 useable
      responses from the partners. Of these, there were 35 paired questionnaires. There
      was good agreement between partners and patients with both the HPS (r = 0.62) and
      the NCIQ (r = 0.80). There was a significant statistical difference in the
      scoring of the Basic Sound Perception subscale between the two groups (P = .039),
      with spouses under-rating performance in this subscale. CONCLUSIONS: For patients
      with cochlear implants, patients' partners corroborate patients' self-reported
      HRQL. In cases in which patients have sensory impairment, there may be an
      additional role for proxy ratings of HRQL to give a more complete assessment of
      functional limitations.

PMID- 24115000
TI  - Increase of the plasma alpha-synuclein levels in patients with multiple system
      atrophy.
AB  - Multiple system atrophy, a sporadic neurodegenerative disease, is characterized
      by the presence of high numbers of glial cytoplasmic inclusions mainly formed by
      alpha-synuclein protein, which is encoded by the SNCA gene. To date, however, few
      studies have investigated the plasma alpha-synuclein levels in patients with
      multiple system atrophy. We studied plasma alpha-synuclein concentrations by
      using an enzyme-linked immunosorbent assay in 74 patients with multiple system
      atrophy and 90 healthy controls. The plasma alpha-synuclein levels were
      significantly elevated in patients who had multiple system atrophy compared with
      the control group (P = 0.000). In a subgroup of 48 patients who had probable
      multiple system atrophy, there was a weakly negative correlation between plasma
      alpha-synuclein levels and subscores on Unified Multiple System Atrophy Rating
      Scale item VI (r(s)  = -0.307; P = 0.034). Plasma alpha-synuclein levels were
      elevated in patients with multiple system atrophy, and these levels may be
      decreased with the development of disease.

PMID- 24115001
TI  - Re: Hogan S, Gammie A, Abrams P. Urodynamic features and artifacts. Neurourol
      urodyn 2012; 31:1104-1117.

PMID- 24115002
TI  - Bile salt export pump expression: can immunohistochemistry in isolation mislead?

PMID- 24115003
TI  - The non-coding skin: exploring the roles of long non-coding RNAs in epidermal
      homeostasis and disease.
AB  - Long non-coding RNAs (lncRNAs) have recently gained increasing attention because
      of their crucial roles in gene regulatory processes. Functional studies using
      mammalian skin as a model system have revealed their role in controlling normal
      tissue homeostasis as well as the transition to a diseased state. Here, we
      describe how lncRNAs regulate differentiation to preserve an undifferentiated
      epidermal progenitor compartment, and to maintain a functional skin permeability
      barrier. Furthermore, we will reflect on recent work analyzing the impact of
      lncRNAs on the progression from normal epithelium to the development of skin
      disorders and cancer. 

PMID- 24115004
TI  - Inherently poor survival of elderly patients with nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to determine the features of the
      elderly patient with nasopharyngeal carcinoma (NPC). METHODS: The medical records
      of 212 patients with NPC, aged >=65 years, and receiving radiotherapy were
      retrospectively reviewed. Comorbidity was rated using the Charlson Comorbidity
      Index (CCI). RESULTS: Twenty-four patients (11.3%) scored >=3 and 188 patients
      (88.7%) scored <3 rated by CCI. The median actuarial irradiated dose of the
      nasopharynx was 72 Gy (range, 20-94 Gy) with 87.3% patients receiving >70 Gy. One
      hundred fifty-four patients had stage III/IV disease. The actuarial local
      control, cancer-specific survival (CSS), and overall survival (OS) rates at 5
      years were 68.8%, 63.5%, and 47.0%, respectively. On multivariate analysis, stage
      (hazard ratio [HR], 1.489; 95% confidence interval [CI], 1.168-1.897; p = .001),
      the technique of radiotherapy (HR, 0.674; 95% CI, 0.476-0.953; p = .025), and
      anemia (HR, 3.081; 95% CI, 1.624-5.845; p = .001) were independent prognostic
      factors. CONCLUSION: The elderly patients with NPC may inherently predict poor
      outcomes.

PMID- 24115005
TI  - Stomach herniation predicts fetal death or non-reassuring fetal status in
      gastroschisis at late pregnancy.

PMID- 24115006
TI  - Effects of fat on MR-measured metabolite signal strengths: implications for in
      vivo MRS studies of the human brain.
AB  - Recent MRS studies have indicated that a higher body mass index (BMI) is
      associated with lower brain metabolite levels. Generally, individuals with higher
      BMIs have more body fat deposits than individuals with normal BMIs. This single
      voxel spectroscopy (SVS) study investigated possible effects of fat on MR
      measured metabolite signal areas, which may at least partly explain the observed
      associations of BMI with MR-measured brain metabolite levels in vivo. SVS data
      were acquired at 4 T from a phantom containing N-acetylaspartate, glutamate and
      creatine, as well as from three healthy male adults. Back fat obtained from pig
      was used to assess the effects of fat on metabolite signals. With the same voxel
      size and placement, the phantom was first scanned without fat (baseline), and
      then with 0.7-cm- and 1.4-cm-thick fat layers placed on it. Each participant was
      also scanned first without fat and then with two 0.7-cm fat layers, one placed
      beneath the occiput and the other on the forehead. Two spectra were acquired per
      participant from the anterior cingulate and the parieto-occipital cortices. The
      metabolite resonance and corresponding water peak areas were then fitted and
      metabolite to water signal ratios were used for analyses. In both phantom and in
      vivo experiments, the metabolite-to-water ratios decreased in the presence of fat
      relative to baseline metabolite-to-water ratios. The reduced metabolite signals
      in the presence of fat reported here are reminiscent of the negative correlations
      observed between BMI and MR-measured metabolite levels. These apparent physical
      effects of fat have potentially far-reaching consequences for the accuracy of MR
      measurements of brain metabolite levels and their interpretation, particularly
      when large fat stores exist around the skull, such as in individuals with higher
      BMI.

PMID- 24115007
TI  - Evaluating the impact a proposed family planning model would have on maternal and
      infant mortality in Afghanistan.
AB  - OBJECTIVE: This study aimed to assess the potential impact a proposed family
      planning model would have on reducing maternal and infant mortality in
      Afghanistan. BACKGROUND: Afghanistan has a high total fertility rate, high infant
      mortality rate, and high maternal mortality rate. Afghanistan also has tremendous
      socio-cultural barriers to and misconceptions about family planning services.
      METHODS: We applied predictive statistical models to a proposed family planning
      model for Afghanistan to better understand the impact increased family planning
      can have on Afghanistan's maternal mortality rate and infant mortality rate. We
      further developed a sensitivity analysis that illustrates the number of maternal
      and infant deaths that can be averted over 5 years according to different
      increases in contraceptive prevalence rates. RESULTS: Incrementally increasing
      contraceptive prevalence rates in Afghanistan from 10% to 60% over the course of
      5 years could prevent 11,653 maternal deaths and 317,084 infant deaths, a total
      of 328,737 maternal and infant deaths averted. CONCLUSION: Achieving goals in
      reducing maternal and infant mortality rates in Afghanistan requires a culturally
      relevant approach to family planning that will be supported by the population.
      The family planning model for Afghanistan presents such a solution and holds the
      potential to prevent hundreds of thousands of deaths.

PMID- 24115008
TI  - Evaluating the validity of quality indicators for colorectal cancer care.
AB  - BACKGROUND: Quality indicators (QI) have been developed to measure quality of
      colorectal cancer care in the Netherlands. The aim of this study is to evaluate
      if these QI consistently assess the quality of colorectal cancer care in a
      hospital (internal consistency) and if these QI correlate with each other
      (construct validity). METHODS: The performance of 85 hospitals participating in
      the Dutch Surgical Colorectal Audit between the 1st of January 2010 and 31st of
      December 2010, were evaluated on nine QI: three process indicators for colon
      cancer, three process indicators for rectal cancer and three outcome indicators.
      Consistency between all process indicators was assessed, and correlations between
      all process and outcome indicators were evaluated for colon and rectal cancer
      care separately. RESULTS: Hospital performance on the nine QI ranged widely.
      There was little consistency between the process indicators in assessing hospital
      performance. Most evaluated process indicators for colorectal cancer care did not
      correlate with each other, but were associated with better hospital specific
      patient outcomes. CONCLUSION: QI on colorectal cancer care do provide
      complementary information. Individual QI are not suitable as a surrogate measure
      for the quality of colorectal cancer care. More comprehensive measures are needed
      for true assessment of hospital performance.

PMID- 24115009
TI  - Bilateral sequential adult cochlear implantation: who should receive priority in
      the context of a constrained health care system?
AB  - Resource allocation decisions have become increasingly necessary as the cost of
      health care habitually increases. Bilateral (second side) adult cochlear
      implantation (CI) is an example of a novel technology with accruing evidence of
      benefit, yet expense has limited universal employ. Currently at our centers,
      bilateral implantation is only provided under research protocol. In this article,
      we discuss the need for a principled approach concerning the distribution of a
      second device, both during this period of investigation and if ultimately an
      insured service. Allocation strategies, while extensively addressed in some
      arenas, have yet to be developed for second-side sequential adult CI. We advocate
      that physicians must assume an explicit role when both caring for individual
      patients as well as administering health care programs. We review social justice
      theories that inform resource allocation macrodecisions, and include a defence of
      age-based considerations. Our approach to patient selection for adult second-side
      CI sequentially considers clinical criteria (directly addressed in the article),
      a willingness to participate in rigorous research, and a 65 year cut-off.
      Ultimately, we employ random blinded selection for allocating bilateral CI among
      the remaining similarly situated individuals. This approach functions impartially
      and in a manner that is transparent for both patient and physician.

PMID- 24115011
TI  - Validity and reliability of the Japanese version of the CARE measure in a general
      medicine outpatient setting.
AB  - BACKGROUND: Empathy is an important attribute in medicine, influencing both the
      process and outcome of consultations. However, there are no validated tools
      available in Japan to gather patient feedback on physicians' empathy. The
      Consultation and Relational Empathy (CARE) Measure developed in the UK is widely
      used internationally. OBJECTIVES: To investigate the psychometric properties of a
      Japanese version of the CARE Measure. METHOD: Following two cycles of translation
      and back translation, the Japanese CARE Measure was completed by 317 patients in
      a primary medical care clinic in Japan. Tests of internal reliability and
      validity included Cronbach's alpha, item-total correlations and factor analysis.
      Predicted associations between CARE Measure score and other variables were
      assessed by Spearman's rho. RESULTS: Low numbers of missing values (8.2-9.8%) and
      'not applicable' responses (0-1.3%) suggested high acceptability and face
      validity of the Japanese CARE Measure. Internal reliability was high (Cronbach's
      alpha 0.984) and was reduced by the removal of any of 10 items. High corrected
      item-total correlations (0.897-0.946) suggested homogeneity. Factor analysis
      showed a single solution with high item loadings (0.917-0.957). Construct
      validity was supported by a significant relationship (Spearman's rho 0.74, P <
      0.001) with overall satisfaction with the consultation. CONCLUSION: The Japanese
      CARE Measure appears to be valid and reliable in a primary medical care setting.
      Further work is required to determine its ability to discriminate between
      doctors.

PMID- 24115010
TI  - Roles of age, length of service and job in work-related injury: a prospective
      study of 63,620 person-years in female workers.
AB  - BACKGROUND: The roles of age, length of service and job in various work-related
      injury types are unknown and deserve investigations among female workers. This
      study assessed their roles in the occurrence of injury. METHODS: Three-year
      prospective study of all 22,952 permanently employed women at the French national
      railway company: 63,620 person-years, 756 injuries with working days lost, coded
      using the company's injury classification derived from that of the French health
      insurance scheme. We investigated the incidence of four types of injury: fall on
      same level, fall to lower level, materials/equipment/objects handling, and other
      injuries. Data were analyzed using negative binomial regression. RESULTS: Workers
      aged <25 were subject to a higher risk for all types of injuries. Older workers
      (45-55 years) were subject to a higher injury risk for fall on same level and
      fall to lower level. For fall on same level as for fall to lower level the
      relative risk decreased steadily with increasing length of service with the
      company, from 1.60 for 1 year to 0.50-0.60 for >=30 years. For injuries due to
      materials/equipment/objects handling the relative risk decreased from 1.05 for
      one year to 0.49 for 5-9 years, and then increased to about 1.50 for 20-29 years
      and >=30 years. CONCLUSIONS: Younger and shorter lengths of service were at risk
      for various types of injuries. Higher length of service was at risk for injury
      due to materials/equipment/objects handling. Preventive measures should consider
      the respective risks associated with age, years of employment and job.

PMID- 24115012
TI  - Predictors of exacerbations of asthma and COPD during one year in primary care.
AB  - AIMS: To investigate the incidence of asthma and chronic obstructive pulmonary
      disease (COPD) exacerbations in primary care during one year and to identify risk
      factors for such events. METHODS: The study was carried out at seven general
      practice offices in Norway. Patients aged 40 years or more registered with a
      diagnosis of asthma and/or COPD the previous 5 years were included. After a
      baseline examination, the participants consulted their GP during exacerbations
      for the following 12 months. A questionnaire on exacerbations during the follow
      up year was distributed to all. Univariable and multivariable logistic regression
      was performed to determine predictors of future exacerbations. RESULTS: Three
      hundred and eighty patients attended the baseline examination and complete follow
      up data were retrieved from 340 patients. COPD as defined by forced expiratory
      volume in the first second of expiration/forced vital capacity (FEV1/FVC) < 0.7,
      was found in 132 (38.8%) patients. One hundred and fifty-nine patients (46.8%)
      experienced one exacerbation or more and 101 (29.7%) two exacerbations or more.
      Patients who had an exacerbation treated with antibiotics or systemic
      corticosteroids or leading to hospitalization the year before baseline (N = 88)
      had the highest risk of getting an exacerbation during the subsequent year (odds
      ratio 9.2), whether the FEV1/FVC was below 0.7 or not. Increased risk of future
      exacerbations was also related to age >= 65 years and limitations in social
      activities, but not to the FEV1. CONCLUSIONS: The study confirms that previous
      exacerbations strongly predict future exacerbations in patients with COPD or
      asthma. Identification and a closer follow-up of patients at risk of such events
      could promote earlier treatment when necessary and prevent a rapid deterioration
      of their condition.

PMID- 24115013
TI  - Patterns of primary care service use by families with young children.
AB  - BACKGROUND: In the UK, early years policy emphasizes that all families should
      have access to support tailored to their individual needs. Knowledge of the
      determinants of health service use should help to inform rational and equitable
      planning and delivery of services to parents. OBJECTIVES: We seek to investigate
      the determinants of primary care service use in families with preschool children.
      METHODS: Determinants of service use in two population cohorts (families with
      children aged 0-1 and 2-3 years) from the Growing Up in Scotland study are
      presented. Services related to use of the family doctor or health visitor for
      information on the child's health or behaviour in the last year. RESULTS: A range
      of socio-demographic determinants were significant predictors of service use on
      multivariate analysis. Determinants of service use differed between the health
      visitor and family doctor. CONCLUSIONS: The analysis provides an insight into the
      determinants and patterns of health service use by families with young children
      at two stages of development. While some of our findings are expected or
      supported by previous research, others highlight areas that require further
      investigation.

PMID- 24115014
TI  - Facile tuning of luminescent platinum(II) Schiff base complexes from yellow to
      near-infrared: photophysics, electrochemistry, electrochemiluminescence and
      theoretical calculations.
AB  - The photophysical and related properties of platinum(II) Schiff base complexes
      can be finely and predictably tuned over a wide range of wavelengths by small and
      easily implemented changes to ligand structure. A series of such complexes,
      differing only in the number and positioning of methoxy substituents on the
      phenoxy ring, were synthesised and their photophysical, electrochemical and
      electrochemiluminescent (ECL) properties investigated. Theoretical calculations
      were performed in order to gain further insight into the relationship between
      structure and properties in these materials. By positioning methoxy groups para
      and/or ortho to either the imine or the oxygen group on the ligand, electron
      density could be directed selectively toward the LUMO or HOMO as required. This
      allowed the emission colour (both photoluminescent and electrochemiluminescent)
      to be tuned over a wide range between 587 and 739 nm. The variation in orbital
      energies was also manifested in the positions of the absorption bands and the
      redox properties of the complexes, as well as in the NMR shifts for the
      uncoordinated ligands. All reported complexes displayed intense
      electrochemiluminescence (ECL), which could be initiated either by annihilation
      or co-reactant pathways. The relationship between the electrochemical and
      photophysical properties and the efficiency of the ECL is discussed. For two of
      the complexes solid-state ECL could be generated from electrodeposited layers of
      the complex.

PMID- 24115015
TI  - The succinated proteome.
AB  - The post-translational modifications (PTMs) of cysteine residues include
      oxidation, S-glutathionylation, S-nitrosylation, and succination, all of which
      modify protein function or turnover in response to a changing intracellular redox
      environment. Succination is a chemical modification of cysteine in proteins by
      the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC).
      Intracellular fumarate concentration and succination of proteins are increased by
      hyperpolarization of the inner mitochondrial membrane, in concert with
      mitochondrial, endoplasmic reticulum (ER) and oxidative stress in 3T3 adipocytes
      grown in high glucose medium and in adipose tissue in obesity and diabetes in
      mice. Increased succination of proteins is also detected in the kidney of a
      fumarase deficient conditional knock-out mouse which develops renal cysts. A wide
      range of proteins are subject to succination, including enzymes, adipokines,
      cytoskeletal proteins, and ER chaperones with functional cysteine residues. There
      is also some overlap between succinated and glutathionylated proteins, suggesting
      that the same low pKa thiols are targeted by both. Succination of adipocyte
      proteins in diabetes increases as a result of nutrient excess derived
      mitochondrial stress and this is inhibited by uncouplers, which discharge the
      mitochondrial membrane potential (DeltaPsim) and relieve the electron transport
      chain. 2SC therefore serves as a biomarker of mitochondrial stress or dysfunction
      in chronic diseases, such as obesity, diabetes, and cancer, and recent studies
      suggest that succination is a mechanistic link between mitochondrial dysfunction,
      oxidative and ER stress, and cellular progression toward apoptosis. In this
      article, we review the history of the succinated proteome and the challenges
      associated with measuring this non-enzymatic PTM of proteins by proteomics
      approaches.

PMID- 24115016
TI  - Polyphenol variability in the fruits and juices of a cider apple progeny.
AB  - BACKGROUND: Polyphenols have a favourable antioxidant potential on human health,
      suggesting that their high content in apple is responsible for the beneficial
      effects of apple consumption. They are also linked to the quality of apple juices
      and ciders since they are predominantly responsible for astringency, bitterness
      and colour. Major phenolic compounds were quantified by liquid chromatography in
      fruits and juices from a cider apple progeny harvested for 3 years. The total
      content of procyanidins and their average degree of polymerisation (DPn) were
      also determined in fruits by phloroglucinolysis. Variability and extraction yield
      of these compounds were determined. RESULTS: The variability observed in the
      progeny was representative of the variability observed in many cider apple
      varieties. Hydroxycinnamic acids were the most extractable group, with an average
      extraction yield of 67%, whereas flavonols and anthocyanins were the least.
      CONCLUSION: This study is the first to introduce variability and extraction
      yields of the main phenolic compounds in both fruits and juices of a cider apple
      progeny. This dataset will be used for an upcoming QTL mapping study, an original
      approach that has never been undertaken for cider apple.

PMID- 24115018
TI  - Unusual presentation of Epstein-Barr virus hepatitis treated successfully with
      valganciclovir.
AB  - Described is the case of a 21-year-old male patient who presented with a severe
      Epstein-Barr virus (EBV) hepatitis. The initial diagnosis was challenging, as the
      patient did not have the typical features of the mononucleosis syndrome and
      despite the severity of the hepatitis, the initial serology was negative. In
      addition the liver biopsy did not show the mononuclear cell infiltration
      typically seen in EBV hepatitis. Later, measurements of EBV DNA showed high
      titers and the patient received a course of oral valganciclovir, following which
      he made a rapid clinical and serological response. This case describes an unusual
      presentation of EBV hepatitis, and adds to the body of evidence supporting its
      treatment with valganciclovir.

PMID- 24115017
TI  - Temporal characterization of lymphatic metastasis in an orthotopic mouse model of
      oral cancer.
AB  - BACKGROUND: The overall mortality rate in cases of head and neck squamous cell
      carcinoma (HNSCC) has not improved over the past 30 years, mostly because of the
      high treatment failure rate among patients with regionally metastatic disease. To
      better understand the pathobiologic processes leading to lymphatic metastasis
      development, there is an urgent need for relevant animal models. METHODS: HNSCC
      cell lines were implanted into the tongues of athymic nude mice. Histology,
      immunohistochemistry, and ex vivo 2-photon microscopy were used to evaluate tumor
      progress and spread. RESULTS: Orthotopic xenografts of different HNSCC cell lines
      produced distinct patterns of survival, tumor histology, disease progression
      rate, and lymph node metastasis development. Remarkably, all injected cell types
      reached the lymph nodes within 24 hours after injection, but not all developed
      metastasis. CONCLUSION: This orthotopic xenograft model closely mimics several
      characteristics of human cancer and could be extremely valuable for translational
      studies focusing on lymphatic metastasis development and pathobiology.

PMID- 24115019
TI  - Color-coded fluorescence imaging of lymph-node metastasis, angiogenesis, and its
      drug-induced inhibition.
AB  - Lymph nodes are often the first target of metastatic cancer which can then
      remetastasize to distant organs. The progression of lymph node metastasis is
      dependent on sufficient blood supply provided by angiogenesis. In the present
      study, we have developed a color-coded imaging model to visualize angiogenesis of
      lymph nodes metastasis using green fluorescent protein (GFP) and red fluorescent
      protein (RFP). Transgenic mice carrying GFP under the control of the nestin
      promoter (ND-GFP mice) were used as hosts. Nascent blood vessels express GFP in
      these mice. B16F10-RFP melanoma cells were injected into the efferent lymph
      vessel of the inguinal lymph node of the ND-GFP nude mice, whereby the melanoma
      cells trafficked to the axillary lymph node. Three days after melanoma
      implantation, ND-GFP-expressing nascent blood vessels were imaged in the axillary
      lymph nodes. Seven days after implantation, ND-GFP-expressing nascent blood
      vessels formed a network in the lymph nodes. ND-GFP-positive blood vessels
      surrounded the tumor mass by 14 days after implantation. However, by 28 days
      after implantation, ND-GFP expression was diminished as the blood vessels
      matured. Treatment with doxorubicin significantly decreased the mean nascent
      blood vessel length per tumor volume. These results show that the dual-color ND
      GFP blood vessels/RFP-tumor model is a powerful tool to visualize and quantitate
      angiogenesis of metastatic lymph nodes as well as for evaluation of its
      inhibition.

PMID- 24115020
TI  - MR imaging of protein folding in vitro employing nuclear-Overhauser-mediated
      saturation transfer.
AB  - MR Z-spectroscopy allows enhanced imaging contrast on the basis of saturation
      transfer between the proton pools of cellular compounds and water, occurring via
      chemical exchange (chemical exchange saturation transfer, CEST) or dipole-dipole
      coupling (nuclear Overhauser effect, NOE). In previous studies, signals observed
      in the aliphatic proton region of Z-spectra have been assigned to NOEs between
      protons in water molecules and protons at the surface of proteins. We
      investigated a possible relationship between the signal strength of NOE peaks in
      Z-spectra obtained at B0 = 7 T and protein structure. Here, we report a
      correlation of NOE-mediated saturation transfer with the structural state of
      bovine serum albumin (BSA), which was monitored by fluorescence spectroscopy.
      Encouraged by CEST signal changes observed in tumor tissue, our observation also
      points to a possible contrast mechanism for MRI sensitive to the structural
      integrity of proteins in cells. Therefore, protein folding should be considered
      as an additional property affecting saturation transfer between water and
      proteins, in combination with the microenvironment and physiological quantities,
      such as metabolite concentration, temperature and pH.

PMID- 24115021
TI  - Increase in activation rate of Pro-Tk-subtilisin by a single nonpolar-to-polar
      amino acid substitution at the hydrophobic core of the propeptide domain.
AB  - Tk-subtilisin (Gly70-Gly398) is a subtilisin homolog from Thermococcus
      kodakarensis. Active Tk-subtilisin is produced from its inactive precursor, Pro
      Tk-subtilisin (Gly1-Gly398), by autoprocessing and degradation of the propeptide
      (Tk-propeptide, Gly1-Leu69). This activation process is extremely slow at
      moderate temperatures owing to high stability of Tk-propeptide. Tk-propeptide is
      stabilized by the hydrophobic core. To examine whether a single nonpolar-to-polar
      amino acid substitution at this core affects the activation rate of Pro-Tk
      subtilisin, the Pro-Tk-subtilisin derivative with the Phe17 -> His mutation (Pro
      F17H), Tk-propeptide derivative with the same mutation (F17H-propeptide), and two
      active-site mutants of Pro-F17H (Pro-F17H/S324A and Pro-F17H/S324C) were
      constructed. The crystal structure of Pro-F17H/S324A was nearly identical to that
      of Pro-S324A, indicating that the mutation does not affect the structure of Pro
      Tk-subtilisin. The refolding rate of Pro-F17H/S324A and autoprocessing rate of
      Pro-F17H/S324C were also nearly identical to those of their parent proteins (Pro
      S324A and Pro-S324C). However, the activation rate of Pro-F17H greatly increased
      when compared with that of Pro-Tk-subtilisin, such that Pro-F17H is efficiently
      activated even at 40 degrees C. The far-UV circular dichroism spectrum of F17H
      propeptide did not exhibit a broad trough at 205-230 nm, which is observed in the
      spectrum of Tk-propeptide. F17H-propeptide is more susceptible to chymotryptic
      degradation than Tk-propeptide. These results suggest that F17H-propeptide is
      unfolded in an isolated form and is therefore rapidly degraded by Tk-subtilisin.
      Thus, destabilization of the hydrophobic core of Tk-propeptide by a nonpolar-to
      polar amino acid substitution is an effective way to increase the activation rate
      of Pro-Tk-subtilisin.

PMID- 24115022
TI  - The Warburg effect then and now: from cancer to inflammatory diseases.
AB  - Inflammatory immune cells, when activated, display much the same metabolic
      profile as a glycolytic tumor cell. This involves a shift in metabolism away from
      oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the
      Warburg effect. The result of this change in macrophages is to rapidly provide
      ATP and metabolic intermediates for the biosynthesis of immune and inflammatory
      proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates
      occurs notably in citrate for lipid biosynthesis, and succinate, which activates
      the transcription factor Hypoxia-inducible factor. In this review we take a look
      at the emerging evidence for a role for the Warburg effect in the immune and
      inflammatory responses. The reprogramming of metabolic pathways in macrophages,
      dendritic cells, and T cells could have relevance in the pathogenesis of
      inflammatory and metabolic diseases and might provide novel therapeutic
      strategies. 

PMID- 24115023
TI  - Biocatalytic Michael-type additions of acetaldehyde to nitroolefins with the
      proline-based enzyme 4-oxalocrotonate tautomerase yielding enantioenriched gamma
      nitroaldehydes.
AB  - Call me Michaelase: The enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously
      catalyzes the Michael-type addition of acetaldehyde to a collection of aromatic
      and aliphatic nitroolefins with high stereoselectivity producing precursors of
      gamma-aminobutyric acid (GABA) analogues. 

PMID- 24115025
TI  - Adipose-derived stem cell-containing hyaluronic acid/alginate hydrogel improves
      vocal fold wound healing.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the
      regenerative efficacy of an injectable hyaluronic acid/mildly cross-linked
      alginate hydrogel (HA/ALG hydrogel) containing human adipose-derived mesenchymal
      stem cells (hAdMSCs) for vocal fold (VF) wound healing. STUDY DESIGN: Animal
      research. METHODS: HA/ALG hydrogel containing hAdMSCs was injected into the VFs
      of rabbits immediately after direct injury. Endoscopic evaluations were performed
      at 1 and 3 months after injury, and functional evaluations of mucosal vibration
      and viscoelastic properties were carried out posteuthanization at 3 months after
      injury. Histopathologic and immunohistochemical evaluations of extracellular
      matrix (ECM) components and of hepatocyte growth factor (HGF) activity were
      conducted in injured VFs. The engraftment of implanted hAdMSCs was investigated
      by detecting fluorescent-labeled cells. RESULTS: The administration of hAdMSCs
      and hAdMSCs in HA/ALG hydrogel produced better macroscopic morphologies than the
      injection of phosphate-buffered saline (PBS). Histologic evaluations revealed
      that treatment with hAdMSCs in HA/ALG produced more favorable ECM changes than
      hAdMSC. In particular, the treatment of hAdMSCs in HA/ALG hydrogel ameliorated
      excessive deposition of collagen type I and increased HGF activity in
      regenerating VFs. hAdMSCs in HA/ALG-treated VFs also exhibited functional
      improvements in viscoelastic properties. hAdMSCs in HA/ALG remained viable in
      recipient VFs at 1 month after transplantation, and some were observed to be
      fostered to differentiate into fibroblasts. CONCLUSIONS: The findings of the
      present study suggest that HA/ALG hydrogel is a promising biomaterial for
      prolonging the retention time of stem cells in VFs and for promotion of VF wound
      healing.

PMID- 24115026
TI  - Neurophysiological characterization of transpinal evoked potentials in human leg
      muscles.
AB  - The objectives of this study were to characterize the neurophysiological
      properties of the compound muscle action potentials (CMAPs) evoked by
      transcutaneous electric stimulation of the spine (tsESS), and the effects of
      tsESS on the soleus H-reflex in seated and standing healthy human subjects. In
      seated semi-prone subjects with the trunk semi-flexed, two re-usable self
      adhering electrodes (cathode), connected to act as one electrode, were placed
      bilaterally on the iliac crests. A re-usable pregelled electrode (anode) was
      placed on the thoracolumbar region at thoracic 10-lumbar 1 and held under
      constant pressure throughout the experiment. CMAPs were recorded bilaterally from
      ankle muscles with subjects seated semi-prone at 1.0, 0.3, 0.2, 0.125, and 0.1 Hz
      following tsESS. The soleus H-reflex, evoked by posterior tibial nerve
      stimulation via conventional methods, was measured following tsESS at inter
      stimulus intervals (ISIs) that ranged from -100 to 100 ms with the subjects
      seated semi-prone and during standing. The tsESS-induced CMAPs were not decreased
      at low stimulation frequencies, and the soleus H-reflex excitability was
      profoundly decreased by tsESS at ISIs that ranged from -5 to 20 ms with the
      subjects seated semi-prone and during standing. CMAPs induced by tsESS may be
      utilized to assess spinal-to-muscle conduction time while bypassing spinal
      motoneuron excitability and tsESS can be used as a modality to decrease spinal
      reflex hyper-excitability in neurological disorders.

PMID- 24115027
TI  - Management and clinical outcome of rectal cancer in patients >= 80 years treated
      in southern France (PACA region) between 2006 and 2008.
AB  - BACKGROUND: Rectal cancer is increasingly prevalent in the elderly patients.
      Their clinical history and outcome after treatment are poorly described. This
      retrospective study was undertaken to provide more data and to compare
      therapeutic strategies to the standard of care for younger patients. PATIENTS AND
      METHODS: Data were retrospectively provided by gastroenterologists, oncologists,
      and gerontologists of Provence-Alpes-Cote-d'Azur (PACA). Patients concerned were
      aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008,
      irrespective of stage and (the) treatment of the disease. Overall survival (OS)
      and relapse-free-survival (RFS) were correlated with patient characteristics and
      treatment. The adopted therapeutic strategy was then compared to the standard-of
      care for younger patients. RESULTS: Median follow-up was 36 months. The 3-year OS
      was 47.4% for the 160 patients analyzed, and 59.2% for the 117 patients treated
      with curative intent. The 3-year RFS was 76.6% in the "curative" population. In
      the multivariate analysis, node status and surgery independently influenced OS,
      while RFS was influenced by age, N status, and gender. For T0-T2 tumors, patients
      were treated similar to younger patients with an OS of 83.6% and a RFS of 95.2%,
      respectively. For T3-T4 tumors, 3-year RFS was 65%, even with a less aggressive
      strategy. CONCLUSION: Surgical resection after evaluation using Comprehensive
      Geriatric Assessment (CGA) should be the standard treatment for localized rectal
      cancer (T0-T2) in elderly patients, as it is in younger patients. For locally
      advanced lesions (T3-T4), results obtained after a conservative approach suggest
      that a non-surgical strategy can be used in elderly patients.

PMID- 24115028
TI  - Is voice therapy effective in the management of vocal fold nodules in children?

PMID- 24115029
TI  - High hsCRP is associated with reduced lung function in structural firefighters.
AB  - BACKGROUND: To assess the association between markers of systemic inflammation
      and pulmonary function in a population of structural firefighters. METHODS: We
      studied male career members of a large Midwestern fire department with
      questionnaires, spirometry, and high-sensitivity C-reactive protein (hsCRP) as a
      biomarker of systemic inflammation. We examined percent predicted forced
      expiratory volume in 1 s (FEV1 %-predicted) and forced vital capacity (FVC%
      predicted). RESULTS: Complete data were available for 401 firefighters. Higher
      hsCRP levels were associated with lower lung function values, after adjusting for
      confounding variables. Specifically, for every twofold increase in log10-hsCRP,
      FEV1 %-predicted decreased by a mean 1.5% (95% CI: 0.4, 2.6%) and FVC%-predicted
      decreased by a mean 1.4% (95% CI: 0.4, 2.3%). CONCLUSION: hsCRP as a biomarker of
      systemic inflammation may indicate reduced lung function in structural
      firefighters.

PMID- 24115030
TI  - Expression of type IIA secretory phospholipase A2 inhibits cholesteryl ester
      transfer protein activity in transgenic mice.
AB  - OBJECTIVE: High circulating levels of group IIA secretory phospholipase A2 (sPLA2
      IIA) activity and mass are independent cardiovascular risk factors. Therefore,
      inhibition of sPLA2-IIA may be a target for the treatment of atherosclerotic
      cardiovascular disease. The present study evaluated the effects of sPLA2-IIA
      inhibition with varespladib acid in a novel mouse model, human apolipoprotein B
      (apoB)/human cholesteryl ester transfer protein (CETP)/human sPLA2-IIA triple
      transgenic mice (TTT) fed a Western-type diet. APPROACH AND RESULTS: sPLA2-IIA
      expression increased atherosclerotic lesion formation in TTT compared with human
      apoB/human CETP double transgenic mice (P<0.01). Varespladib acid effectively
      inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of
      varespladib acid to TTT had no impact on atherosclerosis, which could be
      attributed to a proatherogenic plasma lipoprotein profile that appears in
      response to sPLA2-IIA inhibition because of increased plasma CETP activity. In
      the TTT model, sPLA2-IIA decreased CETP activity by reducing the acceptor
      properties of sPLA2-IIA-modified very low-density lipoproteins specifically
      because of a significantly lower apoE content. Increasing very low-density
      lipoprotein-apoE content by means of adenovirus-mediated gene transfer in sPLA2
      IIA transgenic mice restored the acceptor properties for CETP. CONCLUSIONS: These
      data show that in a humanized triple transgenic mouse model with
      hypercholesterolemia, sPLA2-IIA inhibition increases CETP activity via increasing
      the very low-density lipoprotein-apoE content, resulting in a proatherogenic
      lipoprotein profile.

PMID- 24115032
TI  - Hyperglycemia-induced secretion of endothelial heparanase stimulates a vascular
      endothelial growth factor autocrine network in cardiomyocytes that promotes
      recruitment of lipoprotein lipase.
AB  - OBJECTIVE: During diabetes mellitus, coronary lipoprotein lipase increases to
      promote the predominant use of fatty acids. We have reported that high glucose
      stimulates active heparanase secretion from endothelial cells to cleave
      cardiomyocyte heparan sulfate and release bound lipoprotein lipase for transfer
      to the vascular lumen. In the current study, we examined whether heparanase also
      has a function to release cardiomyocyte vascular endothelial growth factor
      (VEGF), and whether this growth factor influences cardiomyocyte fatty acid
      delivery in an autocrine manner. APPROACH AND RESULTS: Acute, reversible
      hyperglycemia was induced in rats, and a modified Langendorff heart perfusion was
      used to separate the coronary perfusate from the interstitial effluent. Coronary
      artery endothelial cells were exposed to high glucose to generate conditioned
      medium, and VEGF release from isolated cardiomyocytes was tested using
      endothelial cell conditioned medium or purified active and latent heparanase.
      Autocrine signaling of myocyte-derived VEGF on cardiac metabolism was studied.
      High glucose promoted latent and active heparanase secretion into endothelial
      cell conditioned medium, an effective stimulus for releasing cardiomyocyte VEGF.
      Intriguingly, latent heparanase was more efficient than active heparanase in
      releasing VEGF from a unique cell surface pool. VEGF augmented cardiomyocyte
      intracellular calcium and AMP-activated protein kinase phosphorylation and
      increased heparin-releasable lipoprotein lipase. CONCLUSIONS: Our data suggest
      that the heparanase-lipoprotein lipase-VEGF axis amplifies fatty acid delivery, a
      rapid and adaptive mechanism that is geared to overcome the loss of glucose
      consumption by the diabetic heart. If prolonged, the resultant lipotoxicity could
      lead to cardiovascular disease in humans.

PMID- 24115031
TI  - Helix-loop-helix factor inhibitor of differentiation 3 regulates interleukin-5
      expression and B-1a B cell proliferation.
AB  - OBJECTIVE: Natural immunity is emerging as an important mediator of protection
      from atherogenesis. Natural IgM antibodies that recognize oxidation-specific
      epitopes on low-density lipoprotein or phospholipids and the B-1a B cells that
      produce them attenuate atherosclerosis. We previously demonstrated that Apoe(-/-)
      mice globally deficient in the helix-loop-helix protein inhibitor of
      differentiation 3 (Id3) develop early diet-induced atherosclerosis. Furthermore,
      B cell-mediated attenuation of atherosclerosis in B cell-deficient mice was
      dependent on Id3. Here, we sought to determine whether Id3 regulates B-1a B cells
      and the natural antibodies that they produce and identify mechanisms mediating
      these effects. APPROACH AND RESULTS: Mice lacking Id3 had significantly fewer B
      1a B cells in the spleen and peritoneal cavity and reduced serum levels of the
      natural antibody E06. B cell-specific deletion of Id3 revealed that this effect
      was not because of the loss of Id3 in B cells. Interleukin (IL)-33 induced
      abundant, Id3-dependent IL-5 production in the recently identified innate
      lymphoid cell, the natural helper (NH) cell, but not Th2 or mast cells. In
      addition, delivery of IL-5 to Id3-deficient mice restored B-1a B cell
      proliferation. B-1a B cells were present in aortic samples also containing NH
      cells. Aortic NH cells produced IL-5, a B-1a B cell mitogen in response to IL-33
      stimulation. CONCLUSIONS: These studies are the first to identify NH and B-1a B
      cells in the aorta and provide evidence that Id3 is a key regulator of NH cell IL
      5 production and B-1a B cell homeostasis.

PMID- 24115033
TI  - Interleukin 6 stimulates endothelial binding and transport of high-density
      lipoprotein through induction of endothelial lipase.
AB  - OBJECTIVE: In the reverse cholesterol transport pathway, high-density lipoprotein
      (HDL) passes the endothelial cell barrier by mechanisms involving the scavenger
      receptor class B type I and the ATP-binding cassette G1. However, little is known
      on how inflammation influences this transendothelial transport. APPROACH AND
      RESULTS: On stimulation with interleukin-6, cultivated primary endothelial cells
      showed increased binding and transport of (125)I-HDL without changing the
      expression of scavenger receptor class B type I and ATP-binding cassette G1.
      Therefore, we analyzed the involvement of endothelial lipase (EL), a known HDL
      binding protein expressed by endothelial cells. Here, we show an increased EL
      expression after interleukin-6 stimulation. Moreover, using pharmacological
      inhibitors or RNA interference against EL, we demonstrated its participation in
      HDL binding and transport through the endothelium. Furthermore, adenovirus
      mediated transfection of endothelial cells with either catalytically active or
      nonactive EL revealed that EL facilitates the endothelial binding and transport
      by both bridging and lipolysis of HDL. EL was also found responsible for the
      reduction of HDL particle size occurring during the specific transport through a
      monolayer of endothelial cells. Finally, pharmacological inhibition of EL
      reversed the inducing effect of interleukin-6 on HDL binding and transport.
      CONCLUSIONS: Interleukin-6 stimulates the translocation of HDL through the
      endothelium, the first step in reverse cholesterol transport pathway, by
      enhancing EL expression. In addition, we demonstrated the role of EL in the
      transendothelial transport of HDL.

PMID- 24115034
TI  - Crucial role for endoplasmic reticulum stress during megakaryocyte maturation.
AB  - OBJECTIVE: Apoptotic-like phase is an essential step for the platelet formation
      from megakaryocytes. How controlled is this signaling pathway remained poorly
      understood. The aim of this study was to determine whether endoplasmic reticulum
      (ER) stress-induced apoptosis occurs during thrombopoiesis. APPROACH AND RESULTS:
      Investigation of ER stress and maturation markers in different models of human
      thrombopoiesis (CHRF, DAMI, MEG-01 cell lines, and hematopoietic stem cells:
      CD34(+)) as well as in immature pathological platelets clearly indicated that ER
      stress occurs transiently during thrombopoiesis. Direct ER stress induction by
      tunicamycin, an inhibitor of N-glycosylation, or by sarco/endoplasmic reticulum
      Ca(2+) ATPase type 3b overexpression, which interferes with reticular calcium,
      leads to some degree of maturation in megakaryocytic cell lines. On the contrary,
      exposure to salubrinal, a phosphatase inhibitor that prevents eukaryotic
      translation initiation factor 2alpha-P dephosphorylation and inhibits ER stress
      induced apoptosis, decreased both expression of maturation markers in MEG-01 and
      CD34(+) cells as well as numbers of mature megakaryocytes and proplatelet
      formation in cultured CD34(+) cells. CONCLUSIONS: Taken as a whole, our research
      suggests that transient ER stress activation triggers the apoptotic-like phase of
      the thrombopoiesis process.

PMID- 24115036
TI  - An unexpected intriguing effect of Toll-like receptor regulator RP105 (CD180) on
      atherosclerosis formation with alterations on B-cell activation.
AB  - OBJECTIVE: In atherosclerosis, Toll-like receptors (TLRs) are traditionally
      linked to effects on tissue macrophages or foam cells. RP105, a structural TLR4
      homolog, is an important regulator of TLR signaling. The effects of RP105 on TLR
      signaling vary for different leukocyte subsets known to be involved in
      atherosclerosis, making it unique in its role of either suppressing (in myeloid
      cells) or enhancing (in B cells) TLR-regulated inflammation in different cell
      types. We aimed to identify a role of TLR accessory molecule RP105 on circulating
      cells in atherosclerotic plaque formation. APPROACH AND RESULTS: Irradiated low
      density lipoprotein receptor deficient mice received RP105(-/-) or wild-type bone
      marrow. RP105(-/-) chimeras displayed a 57% reduced plaque burden. Interestingly,
      total and activated B-cell numbers were significantly reduced in RP105(-/-)
      chimeras. Activation of B1 B cells was unaltered, suggesting that RP105
      deficiency only affected inflammatory B2 B cells. IgM levels were unaltered, but
      anti-oxidized low-density lipoprotein and anti-malondialdehyde-modified low
      density lipoprotein IgG2c antibody levels were significantly lower in RP105(-/-)
      chimeras, confirming effects on B2 B cells rather than B1 B cells. Moreover, B
      cell activating factor expression was reduced in spleens of RP105(-/-) chimeras.
      CONCLUSIONS: RP105 deficiency on circulating cells results in an intriguing
      unexpected TLR-associated mechanisms that decrease atherosclerotic lesion
      formation with alterations on proinflammatory B2 B cells.

PMID- 24115035
TI  - Adenosine monophosphate-activated protein kinase-alpha2 deficiency promotes
      vascular smooth muscle cell migration via S-phase kinase-associated protein 2
      upregulation and E-cadherin downregulation.
AB  - OBJECTIVE: Abnormal proliferation and migration of vascular smooth muscle cells
      (VSMCs) are critical events in the progression of several vasculopathologies.
      Adenosine monophosphate-activated protein kinase (AMPK) has been shown to play a
      pivotal role in cellular proliferation and migration. However, the roles of AMPK
      in VSMC migration and its underlying molecular mechanisms remain elusive.
      APPROACH AND RESULTS: VSMC migration and the neointima formation were studied in
      cultured mouse VSMCs or in carotid artery ligation of wild-type C57BL/6J mice,
      AMPKalpha2, AMPKalpha1 homozygous-deficient (AMPKalpha2(-/-), AMPKalpha1(-/-))
      mice. Deletion of AMPKalpha2, but not AMPKalpha1, led to increased
      phosphorylation of both IkB kinase alpha and its downstream target nuclear factor
      kB2/p100 at serine 866/870. Consequently, phosphor-p100 at S866/870 bound with E3
      ubiquitin ligase beta-transducin repeat-containing protein resulting in the
      proteolytic processing of the p100 precursor and nuclear factor kB2/p52
      induction. Interestingly, acetylation of histone H3 at lysine 56 mediated by
      histone deacetylase-3 reduction was enhanced significantly in AMPKalpha2(-/-)
      VSMCs compared with wild-type or AMPKalpha1(-/-) VSMCs. Moreover, the augmented
      association of p52/acetylation of histone H3 at lysine 56 with the promoter of
      ubiquitin E3 ligase, S-phase kinase-associated protein 2, was shown in
      AMPKalpha2(-/-) VSMCs by chromatin immunoprecipitation assay. Furthermore,
      AMPKalpha2 deletion caused S-phase kinase-associated protein 2-mediated E
      cadherin downregulation. S-Phase kinase-associated protein 2 siRNA abolished the
      increased migration of AMPKalpha2(-/-) VSMCs via E-cadherin upregulation.
      Finally, neointima formation after ligation of carotid artery was increased in
      AMPKalpha2(-/-), but not AMPKalpha1(-/-), mice. CONCLUSIONS: We conclude that
      deletion of AMPKalpha2 causes aberrant VSMC migration with accelerated neointima
      formation in vivo.

PMID- 24115037
TI  - Self-induced plantar-flexion objectively reduces wave amplitude of detrusor
      overactivity and subjectively improve urinary urgency: a pilot study.
AB  - AIMS: To estimate the effect of plantar-flexion on the wave amplitude of
      involuntary detrusor contraction and the severity of urinary urgency during
      filling cystometry in patients with detrusor overactivity (DO). METHODS: Twenty
      two consecutive patients with DO were enrolled. During urodynamics, the mean peak
      detrusor pressures of each contraction were documented and compared. At the
      beginning of the 2nd or 3rd wave, patients were asked to perform continuous
      plantar-flexion by pushing their tiptoes against the floor. Following each wave,
      patients were asked to grade the severity of the urgency by a visual analogue
      scale (VAS). RESULTS: The mean peak detrusor pressure without plantar-flexion was
      58 cmH2 O (95% CI: 46.3-69.7) compared to 31 cmH2 O (95% CI: 23.1-38.9) with
      plantar-flexion (P < 0.001). All patients reported a reduced degree of urgency
      during plantar-flexion reflected in a significant reduction in mean VAS score
      from 9.3 (95% CI: 9-9.5) to 4.7 (95% CI: 3.9-5.4; P < 0.0001). CONCLUSIONS: Self
      performed plantar-flexion maneuver might reduce the severity of urinary urgency
      and the magnitude of overactive detrusor contractions, which may have a role in
      the conservative therapy of detrusor overactivity.

PMID- 24115038
TI  - Anti-lymphangiogenesis effects of a specific anti-interleukin 7 receptor antibody
      in lung cancer model in vivo.
AB  - Interleukin 7 (IL-7) is known to promote lymphangiogenesis. To study the
      relationship between IL-7 and the lymphangiogenesis in lung cancer cells
      xenograft tumors, we investigated how IL-7 regulates lymphangiogenesis by
      Quantitative real-time reverse transcriptase-polymerase chain reaction, Western
      blot, co-immunoprecipitation, chromatin immunoprecipitation, and
      immunohistochemistry methods. We found that, in lung cancer cells xenograft
      tumors IL-7/IL-7 receptor (IL-7R) increase the expression of VEGF-D and
      lymphangiogenesis, induce c-Fos and c-Jun heterodimer formation, and enhance c
      Fos/c-Jun DNA binding activity to regulate VEGF-D. Taken together, our results
      provided evidence that IL-7/IL-7R induce VEGF-D upregulation and promote
      lymphangiogenesis via c-Fos/c-Jun pathway in lung cancer.

PMID- 24115039
TI  - Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes:
      updated criteria and genotype assignment web resource.
AB  - The 2005 consensus proposal for the classification of hepatitis C virus (HCV)
      presented an agreed and uniform nomenclature for HCV variants and the criteria
      for their assignment into genotypes and subtypes. Since its publication, the
      available dataset of HCV sequences has vastly expanded through advancement in
      nucleotide sequencing technologies and an increasing focus on the role of HCV
      genetic variation in disease and treatment outcomes. The current study represents
      a major update to the previous consensus HCV classification, incorporating
      additional sequence information derived from over 1,300 (near-)complete genome
      sequences of HCV available on public databases in May 2013. Analysis resolved
      several nomenclature conflicts between genotype designations and using consensus
      criteria created a classification of HCV into seven confirmed genotypes and 67
      subtypes. There are 21 additional complete coding region sequences of unassigned
      subtype. The study additionally describes the development of a Web resource
      hosted by the International Committee for Taxonomy of Viruses (ICTV) that
      maintains and regularly updates tables of reference isolates, accession numbers,
      and annotated alignments (http://talk.ictvonline.org/links/hcv/hcv
      classification.htm). The Flaviviridae Study Group urges those who need to check
      or propose new genotypes or subtypes of HCV to contact the Study Group in advance
      of publication to avoid nomenclature conflicts appearing in the literature. While
      the criteria for assigning genotypes and subtypes remain unchanged from previous
      consensus proposals, changes are proposed in the assignment of provisional
      subtypes, subtype numbering beyond "w," and the nomenclature of intergenotypic
      recombinant. CONCLUSION: This study represents an important reference point for
      the consensus classification of HCV variants that will be of value to researchers
      working in clinical and basic science fields.

PMID- 24115040
TI  - Part I: the development of the catalytic Wittig reaction.
AB  - We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The
      utilization of an organosilane was pivotal for success as it allowed for the
      chemoselective reduction of a phosphane oxide. Protocol optimization evaluated
      the phosphane oxide precatalyst structure, loading, organosilane, temperature,
      solvent, and base. These studies demonstrated that to maintain viable catalytic
      performance it was necessary to employ cyclic phosphane oxide precatalysts of
      type 1. Initial substrate studies utilized sodium carbonate as a base, and
      further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble
      alternative. The use of DIPEA improved the ease of use, broadened the substrate
      scope, and decreased the precatalyst loading. The optimized protocols were
      compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl,
      and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate
      to-high yields (60-96%) by using a precatalyst loading of 4-10 mol%. Kinetic E/Z
      selectivity was generally 66:34; complete E selectivity for disubstituted
      alpha,beta-unsaturated products was achieved through a phosphane-mediated
      isomerization event. The CWR was applied to the synthesis of 54, a known
      precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram
      scale (12.2 g, 74% yield). In addition, to our knowledge, the described CWR is
      the only transition-/heavy-metal-free catalytic olefination process, excluding
      proton-catalyzed elimination reactions.

PMID- 24115042
TI  - Metastatic melanoma to the upper aerodigestive tract: a systematic review of the
      literature.
AB  - This study is a systematic review of the literature that was performed to clarify
      the natural history and treatment outcomes of upper aerodigestive tract
      metastases from cutaneous melanoma. A search of the MEDLINE database was
      undertaken from 1950 to 2013 to identify relevant manuscripts for this review.
      Article inclusion required cases with documentation of previous cutaneous
      melanoma primary lesions, adequate survival data, and description of metastatic
      treatment. Individual patient data were extracted from source articles for
      analysis of survival outcomes. A systematic search revealed 34 relevant articles
      with 37 cases for inclusion. Metastases were identified throughout the upper
      aerodigestive tract with a predilection for the oropharynx, larynx, and oral
      cavity. Treatment outcomes were estimated with the Kaplan-Meier method, with
      survival of 37% and 16% at 1 and 5 years, respectively. As expected from previous
      reports, 73% presented with disseminated disease burden with almost universally
      poor prognosis despite locoregional or systemic therapy. Conversely, a group of
      patients with limited metastatic burden had improved treatment response with a 1
      year survival of 90%, denoting a hazard ratio of 9.7332 (95% confidence interval,
      4.5-21.1) for disseminated disease in comparison. Upper aerodigestive tract
      metastases of melanoma thus are rare clinical entities that in general present in
      the setting of disseminated disease and evidently necessitate a focus on
      palliation. In contrast, for those with a limited metastatic burden, aggressive
      multimodality therapy including complete metastectomy can produce a significant
      survival advantage.

PMID- 24115041
TI  - Natural and lesion-induced decrease in cell proliferation in the medial nucleus
      of the trapezoid body during hearing development.
AB  - The functional interactions between neurons and glial cells that are important
      for nervous system function are presumably established during development from
      the activity of progenitor cells. In this study we examined proliferation of
      progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in
      the rat auditory brainstem. We performed DNA synthesis labeling experiments to
      demonstrate changes in cell proliferation activity during postnatal stages of
      development. An increase in cell proliferation correlated with MNTB growth and
      the presence of S100beta-positive astrocytes among MNTB neurons. In additional
      experiments we analyzed the fate of newly born cells. At perinatal ages, newly
      born cells colabeled with the astrocyte marker S100beta in higher numbers than
      when cells were generated at postnatal day 6. Furthermore, we identified newly
      born cells that were colabeled with caspase-3 immunohistochemistry and performed
      comparative experiments to demonstrate that there is a natural decrease in cell
      proliferation activity during postnatal development in rats, mice, gerbils, and
      ferrets. Lastly, we found that there is a stronger decrease in MNTB cell
      proliferation after performing bilateral lesions of the auditory periphery in
      rats. Altogether, these results identify important stages in the development of
      astrocytes in the MNTB and provide evidence that the proliferative activity of
      the progenitor cells is developmentally regulated. We propose that the
      developmental reduction in cell proliferation may reflect coordinated signaling
      between the auditory brainstem and the auditory periphery.

PMID- 24115043
TI  - Thyroid hemiagenesis associated with medullary or papillary carcinoma: report of
      cases.
AB  - BACKGROUND: Thyroid hemiagenesis is a rare congenital anomaly in which 1 thyroid
      lobe fails to develop. Co-occurrence of hemiagenesis and thyroid carcinoma is
      extremely rare. Here, we report 2 cases of thyroid hemiagenesis with carcinoma.
      METHODS: The first patient was referred with a left thyroid mass and absent right
      lobe. The frozen section examination revealed medullary thyroid carcinoma (MTC);
      therefore, a left thyroid lobectomy plus neck dissection was performed. Another
      patient was referred with a right thyroid mass and absent left lobe. Fine-needle
      aspiration biopsy was suspicious for papillary carcinoma. The patient underwent
      right thyroid lobectomy plus neck dissection. RESULTS: The operative findings
      confirmed hemiagenesis of the right lobe and MTC in the left lobe for the first
      case, and hemiagenesis of the left lobe and papillary carcinoma in the right lobe
      for the second case. CONCLUSION: Our case represents the first reported case of
      association between thyroid hemiagenesis and MTC.

PMID- 24115044
TI  - Abnormal maximal finger tapping in abstinent cannabis users.
AB  - OBJECTIVE: To investigate movement speed and rhythmicity in abstinent cannabis
      users, we hypothesized that abstinent cannabis users exhibit decreased maximal
      finger tapping frequency and increased variability of tapping compared with non
      drug users. METHODS: The study involved 10 healthy adult cannabis users and 10
      age-matched and gender-matched controls with no history of illicit drug use.
      Subjects underwent a series of screening tests prior to participation. Subjects
      were then asked to tap a strain gauge as fast as possible with the index finger
      of their dominant hand (duration 5 s). RESULTS: The average intertap interval did
      not significantly differ between groups, but the coefficient of variation of the
      intertap interval was significantly greater in the cannabis group than in
      controls (p=0.011). The cannabis group also exhibited a slow tapping frequency at
      the beginning of the task. CONCLUSIONS: Rhythmicity of finger tapping is abnormal
      in individuals with a history of cannabis use. The abnormality appears to be long
      lasting and adds to the list of functional changes present in abstinent cannabis
      users.

PMID- 24115045
TI  - Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell
      cultures.
AB  - The recent development of dissolution dynamic nuclear polarization (DNP) gives
      NMR the sensitivity to follow metabolic processes in living systems with high
      temporal resolution. In this article, we apply dissolution DNP to study the
      metabolism of hyperpolarized U-(13)C,(2)H7-glucose in living, perfused human
      breast cancer cells. Spectrally selective pulses were used to maximize the signal
      of the main product, lactate, whilst preserving the glucose polarization; in this
      way, both C1-lactate and C3-lactate could be observed with high temporal
      resolution. The production of lactate by T47D breast cancer cells can be
      characterized by Michaelis-Menten-like kinetics, with K(m) = 3.5 +/- 1.5 mM and
      V(max) = 34 +/- 4 fmol/cell/min. The high sensitivity of this method also allowed
      us to observe and quantify the glycolytic intermediates dihydroxyacetone
      phosphate and 3-phosphoglycerate. Even with the enhanced DNP signal, many other
      glycolytic intermediates could not be detected directly. Nevertheless, by
      applying saturation transfer methods, the glycolytic intermediates glucose-6
      phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, glyceraldehyde-3
      phosphate, phosphoenolpyruvate and pyruvate could be observed indirectly. This
      method shows great promise for the elucidation of the distinctive metabolism and
      metabolic control of cancer cells, suggesting multiple ways whereby
      hyperpolarized U-(13)C,(2)H7-glucose NMR could aid in the diagnosis and
      characterization of cancer in vivo.

PMID- 24115047
TI  - Palladium-catalyzed asymmetric benzylation of azlactones.
AB  - Asymmetric benzylation of prochiral azlactone nucleophiles enables the catalytic
      introduction of a benzyl group towards the synthesis of alpha,alpha-disubstituted
      amino acids. Herein, we report an enantioselective palladium-catalyzed process
      using chiral bis(diphenylphosphinobenzoyl)diamine (dppba) ligands. Naphthalene-
      and heterocycle-based methyl carbonates react with a number of azlactones derived
      from both natural and unnatural amino acids. Monocyclic benzylic electrophiles,
      for which the barrier to ionization is higher, must employ a phosphate leaving
      group in order to react. Reaction conditions for electron-rich and -neutral
      benzylic electrophiles have been developed, and the scope of the reaction has
      been explored with respect to both reaction partners. The high levels of
      asymmetric induction, as well as the reactivity pattern of the electrophiles,
      suggest an eta(3)-benzyl intermediate that arises through two distinct pathways.

PMID- 24115046
TI  - Recombinant human lecithin-cholesterol acyltransferase Fc fusion: analysis of N-
      and O-linked glycans and identification and elimination of a xylose-based O
      linked tetrasaccharide core in the linker region.
AB  - Recombinant human lecithin-cholesterol acyltransferase Fc fusion (huLCAT-Fc) is a
      chimeric protein produced by fusing human Fc to the C-terminus of the human
      enzyme via a linker sequence. The huLCAT-Fc homodimer contains five N-linked
      glycosylation sites per monomer. The heterogeneity and site-specific distribution
      of the various glycans were examined using enzymatic digestion and LC-MS/MS,
      followed by automatic processing. Almost all of the N-linked glycans in human
      LCAT are fucosylated and sialylated. The predominant LCAT N-linked glycoforms are
      biantennary glycans, followed by triantennary sugars, whereas the level of
      tetraantennary glycans is much lower. Glycans at the Fc N-linked site exclusively
      contain typical asialobiantennary structures. HuLCAT-Fc was also confirmed to
      have mucin-type glycans attached at T407 and S409 . When LCAT-Fc fusions were
      constructed using a G-S-G-G-G-G linker, an unexpected +632 Da xylose-based
      glycosaminoglycan (GAG) tetrasaccharide core of Xyl-Gal-Gal-GlcA was attached to
      S418 . Several minor intermediate species including Xyl, Xyl-Gal, Xyl-Gal-Gal,
      and a phosphorylated GAG core were also present. The mucin-type O-linked glycans
      can be effectively released by sialidase and O-glycanase; however, the GAG could
      only be removed and localized using chemical alkaline beta-elimination and
      targeted LC-MS/MS. E416 (the C-terminus of LCAT) combined with the linker
      sequence is likely serving as a substrate for peptide O-xylosyltransferase.
      HuLCAT-Fc shares some homology with the proposed consensus site near the linker
      sequence, in particular, the residues underlined PPPE416 GS418 GGGGDK. GAG
      incorporation can be eliminated through engineering by shifting the linker Ser
      residue downstream in the linker sequence. 

PMID- 24115048
TI  - 3'UTRs take a long shot in the brain.
AB  - The fast advancing RNA-seq technology has unveiled an unexpected diversity and
      expression specificity of 3' untranslated regions (3'UTRs) of mRNAs. In
      particular, neural mRNAs seem to express significantly longer 3'UTRs, some of
      which are over 10 kb in length. The extensive elongation of 3'UTRs in neural
      tissues provides intriguing possibilities for cell type-specific regulations that
      are governed by miRNAs, RNA-binding proteins and ribonucleoprotein aggregates. In
      this article, we review recent progress in the characterization of mRNA 3'UTRs
      and discuss their implications in the understanding of 3'UTR-mediated gene
      regulation.

PMID- 24115049
TI  - Intracellular gene transcription factor protein-guided MRI by DNA aptamers in
      vivo.
AB  - The mechanisms by which transcription factor (TF) protein AP-1 modulates
      amphetamine's effects on gene transcription in living brains are unclear. We
      describe here the first part of our studies to investigate these mechanisms,
      specifically, our efforts to develop and validate aptamers containing the binding
      sequence of TF AP-1 (5ECdsAP1), in order to elucidate its mechanism of action in
      living brains. This AP-1-targeting aptamer, as well as a random sequence aptamer
      with no target (5ECdsRan) as a control, was partially phosphorothioate modified
      and tagged with superparamagnetic iron oxide nanoparticles (SPIONs), gold, or
      fluorescein isothiothianate contrast agent for imaging. Optical and transmission
      electron microscopy studies revealed that 5ECdsAP1 is taken up by endocytosis and
      is localized in the neuronal endoplasmic reticulum. The results of magnetic
      resonance imaging (MRI) with SPION-5ECdsAP1 revealed that neuronal AP-1 TF
      protein levels were elevated in neurons of live male C57black6 mice after
      amphetamine exposure; however, pretreatment with SCH23390, a dopaminergic
      receptor antagonist, suppressed this elevation. As studies in transgenic mice
      with neuronal dominant-negative A-FOS mutant protein, which has no binding
      affinity for the AP-1 sequence, showed a completely null MRI signal in the
      striatum, we can conclude that the MR signal reflects specific binding between
      the 5ECdsAP1 aptamer and endogenous AP-1 protein. Together, these data lend
      support to the application of 5ECdsAP1 aptamer for intracellular protein-guided
      imaging and modulation of gene transcription, which will thus allow investigation
      of the mechanisms of signal transduction in living brains.

PMID- 24115050
TI  - Comparing the effects of mitochondrial targeted and localized antioxidants with
      cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide.
AB  - Skin cancer and aging are linked to increased cellular reactive oxygen species
      (ROS), particularly following exposure to ultraviolet A (UVA) in sunlight. As
      mitochondria are the main source of cellular ROS, this study compared the
      protective effects of mitochondria-targeted and -localized antioxidants (MitoQ
      and tiron, respectively) with cellular antioxidants against oxidative stress
      induced [UVA and hydrogen peroxide (H2O2)] mitochondrial DNA (mtDNA) damage in
      human dermal fibroblasts. With the use of a long quantitative PCR assay, tiron
      (EC50 10 mM) was found to confer complete (100%) protection (P<0.001) against
      both UVA- and H2O2-induced mtDNA damage, whereas MitoQ (EC50 750 nM) provided
      less protection (17 and 32%, respectively; P<0.05). This particular protective
      effect of tiron was greater than a range of cellular antioxidants investigated.
      The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway provides
      cellular protection against oxidative stress. An ELISA assay for the Nrf2 target
      gene heme oxygenase-1 (HO-1) and studies using Nrf2 small interfering RNA both
      indicated that tiron's mode of action was Nrf2 independent. The comet assay
      showed that tiron's protective effect against H2O2-induced nuclear DNA damage was
      greater than the cellular antioxidants and MitoQ (P<0.001). This study provides a
      platform to investigate molecules with similar structure to tiron as potent and
      clinically relevant antioxidants.

PMID- 24115051
TI  - Identification of volatile compounds associated with the aroma of white
      strawberries (Fragaria chiloensis).
AB  - BACKGROUND: Fragaria chiloensis (L.) Mill spp. chiloensis form chiloensis, is a
      strawberry that produces white fruits with unique aromas. This species, endemic
      to Chile, is one of the progenitors of Fragaria x ananassa Duch. In order to
      identify the volatile compounds that might be responsible for aroma, these were
      extracted, and analyzed by gas chromatography-mass spectrometry (GC-MS), gas
      chromatography-olfactometry (GC-O) and compared with sensory analyses. RESULTS:
      Three methods of extraction were used: solvent-assisted evaporation (SAFE),
      headspace solid phase micro-extraction (HS-SPME) and liquid-liquid extraction
      (LLE). Ninety-nine volatile compounds were identified by GC-MS, of which 75
      showed odor activity using GC-O. Based on the highest dilution factor (FD = 1000)
      and GC-O intensity >=2, we determined 20 major compounds in white strawberry
      fruit that contribute to its aroma. We chose 51 compounds to be tested against
      their commercial standards. The identities were confirmed by comparison of their
      linear retention indices against the commercial standards. The aroma of white
      strawberry fruits was reconstituted with a synthetic mixture of most of these
      compounds. CONCLUSION: The volatile profile of white strawberry fruit described
      as fruity, green-fresh, floral, caramel, sweet, nutty and woody will be a useful
      reference for future strawberry breeding programs.

PMID- 24115052
TI  - Simultaneous confidence intervals for a success probability and intraclass
      correlation, with an application to screening mammography.
AB  - This paper provides asymptotic simultaneous confidence intervals for a success
      probability and intraclass correlation of the beta-binomial model, based on the
      maximum likelihood estimator approach. The coverage probabilities of those
      intervals are evaluated. An application to screening mammography is presented as
      an example. The individual and simultaneous confidence intervals for sensitivity
      and specificity and the corresponding intraclass correlations are investigated.
      Two additional examples using influenza data and sex ratio data among sibships
      are also considered, where the individual and simultaneous confidence intervals
      are provided. 

PMID- 24115053
TI  - The many faces of asthma in obesity.
AB  - Obesity is a major risk factor for the development of asthma, and causes severe,
      uncontrolled disease that responds poorly to therapy. The obese state alters
      early onset allergic asthma, and leads to the development of a novel form of late
      onset asthma secondary to obesity. The presentation of early onset allergic
      asthma is altered through effects on immune function. Factors such as mechanical
      loading, effects of adipokines on airways, altered diet, insulin resistance and
      altered metabolism of nitric oxide likely all contribute to increased airway
      reactivity in obesity, causing late onset asthma in obesity. Obesity also alters
      responses to environmental factors such as ozone and particulate matter. Focused
      studies to understand the importance of these factors in the pathogenesis of
      airway disease in obesity will be essential to develop therapies to intervene in
      this new epidemic of airway disease.

PMID- 24115054
TI  - A kinematic model of Karman gaiting in rainbow trout.
AB  - A mechanistic understanding of how fishes swim in unsteady flows is challenging
      despite its prevalence in nature. Previous kinematic studies of fish Karman
      gaiting in a vortex street behind a cylinder only report time-averaged
      measurements, precluding our ability to formally describe motions on a cycle-by
      cycle basis. Here we present the first analytical model that describes the
      swimming kinematics of Karman gaiting trout with 70-90% accuracy. We found that
      body bending kinematics can be modelled with a travelling wave equation, which
      has also been shown to accurately model free-stream swimming kinematics. However,
      free-stream swimming and Karman gaiting are separated in the parameter space; the
      amplitude, wavelength and frequency values of the traveling wave equation are
      substantially different for each behavior. During Karman gaiting, the wave is
      initiated at the body center, which is 0.2L (where L is total body length)
      further down the body compared with the initiation point in free-stream swimming.
      The wave travels with a constant speed, which is higher than the nominal flow
      speed just as in free-stream swimming. In addition to undulation, we observed
      that Karman gaiting fish also exhibit substantial lateral translations and body
      rotations, which can constitute up to 75% of the behavior. These motions are
      periodic and their frequencies also match the vortex shedding frequency. There is
      an inverse correlation between head angle and body angle: when the body rotates
      in one direction, the head of the fish turns into the opposite direction. Our
      kinematic model mathematically describes how fish swim in vortical flows in real
      time and provides a platform to better understand the effects of flow variations
      as well as the contribution of muscle activity during corrective motions. 

PMID- 24115055
TI  - Non-stressful temperature effect on oxidative balance and life history traits in
      adult fish (Oryzias latipes).
AB  - Temperature is well known to affect many biological and ecological traits,
      especially in ectotherms. From a physiological point of view, temperature is also
      positively correlated to metabolism and is often associated with an increase in
      reactive oxygen species (ROS) production. It has recently been suggested that ROS
      play a role in lifespan and resource allocation. However, only a few authors have
      attempted to explore the relationships between temperature, resource allocation
      and oxidative balance in ectotherms. Here, we measured the effect of temperature
      on growth, reproductive effort, offspring quantity and quality, hatching and
      survival rates, and the associated proximal costs, which were evaluated through
      the quantification of oxidative balance elements. We reared adult fish (Oryzias
      latipes) at two non-stressful temperatures (20 and 30 degrees C) during a
      relatively long period (4 months, approximately the entire adult life). The
      results show a trade-off between reproduction and maintenance because investment
      toward growth could be neglected at the adult stage (confirmed by our results).
      Intriguingly, ROS-dependent damages did not differ between the two groups,
      probably because of the higher rate of activation of the antioxidant enzyme
      superoxide dismutase for warm-acclimated fish. The allocation toward antioxidant
      defences is associated with an earlier reproduction and a lower quality of
      offspring. These interesting results bring new perspectives in terms of the
      prediction of the impact of global warming on biota through the use of ecological
      theories based on oxidative balance and metabolism. 

PMID- 24115056
TI  - Disruptive communication: stealth signaling in the toadfish.
AB  - Male oyster toadfish, Opsanus tau, produce long duration (250 to 650 ms) sexual
      advertisement calls or 'boatwhistles' during the breeding season. When males are
      in close proximity, the fishes alternate the production of boatwhistles with
      other males to avoid call overlap. However, males can also produce a number of
      different sounds, including a single, short duration pulse or 'grunt' (~100 ms).
      The vocalizations of competing males were recorded in situ with multiple
      hydrophones to examine intraspecific interactions. These short grunts were
      emitted almost exclusively during the boatwhistle of a conspecific male. The
      fundamental frequency (or pulse repetition rate) of the boatwhistles were
      modified by this disruptive grunt, 'jamming' the signal and decreasing its
      frequency. The disruptive grunt specifically targeted the second stage or tonal
      portion of the boatwhistle, believed to be the primary acoustic attractant for
      females, and its brevity and precision may allow its emitter to remain
      undetectable. While the acoustic repertoire of teleost fishes may be less diverse
      compared with terrestrial species, the disruptive grunts indicate fish have the
      capacity for complex acoustic interactions. 

PMID- 24115057
TI  - Gecko toe and lamellar shear adhesion on macroscopic, engineered rough surfaces.
AB  - The role in adhesion of the toes and lamellae - intermediate-sized structures -
      found on the gecko foot remains unclear. Insight into the function of these
      structures can lead to a more general understanding of the hierarchical nature of
      the gecko adhesive system, but in particular how environmental topology may
      relate to gecko foot morphology. We sought to discern the mechanics of the toes
      and lamellae by examining gecko adhesion on controlled, macroscopically rough
      surfaces. We used live Tokay geckos, Gekko gecko, to observe the maximum shear
      force a gecko foot can attain on an engineered substrate constructed with
      sinusoidal patterns of varying amplitudes and wavelengths in sizes similar to the
      dimensions of the toes and lamellae structures (0.5 to 6 mm). We found shear
      adhesion was significantly decreased on surfaces that had amplitudes and
      wavelengths approaching the lamella length and inter-lamella spacing, losing 95%
      of shear adhesion over the range tested. We discovered that the toes are capable
      of adhering to surfaces with amplitudes much larger than their dimensions even
      without engaging claws, maintaining 60% of shear adhesion on surfaces with
      amplitudes of 3 mm. Gecko adhesion can be predicted by the ratio of the lamella
      dimensions to surface feature dimensions. In addition to setae, remarkable
      macroscopic-scale features of gecko toes and lamellae that include compliance and
      passive conformation are necessary to maintain contact, and consequently,
      generate shear adhesion on macroscopically rough surfaces. Findings on the larger
      scale structures in the hierarchy of gecko foot function could provide the
      biological inspiration to drive the design of more effective and versatile
      synthetic fibrillar adhesives. 

PMID- 24115058
TI  - Interactive effects of competition and predator cues on immune responses of
      leopard frogs at metamorphosis.
AB  - Recent hypotheses suggest that immunosuppression, resulting from altered
      environmental conditions, may contribute to the increased incidence of amphibian
      disease around the world. Antimicrobial peptides (AMPs) in amphibian skin are an
      important innate immune defense against fungal, viral and bacterial pathogens.
      Their release is tightly coupled with release of the stress hormone noradrenaline
      (norepinephrine). During metamorphosis, AMPs may constitute the primary immune
      response in the skin of some species because acquired immune functions are
      temporarily suppressed in order to prevent autoimmunity against new adult
      antigens. Suppression of AMPs during this transitional stage may impact disease
      rates. We exposed leopard frog tadpoles (Lithobates pipiens) to a factorial
      combination of competitor and caged-predator environments and measured their
      development, growth and production of hydrophobic skin peptides after
      metamorphosis. In the absence of predator cues, or if the exposure to predator
      cues was late in ontogeny, competition caused more than a 250% increase in mass
      standardized hydrophobic skin peptides. Predator cues caused a decrease in mass
      standardized hydrophobic skin peptides when the exposure was late in ontogeny
      under low competition, but otherwise had no effect. Liquid chromatography tandem
      mass spectrometry of the skin peptides showed that they include six AMPs in the
      brevinin and temporin families and at least three of these peptides are
      previously uncharacterized. Both of these peptide families have previously been
      shown to inhibit harmful microbes including Batrachochytrium dendrobatidis, the
      fungal pathogen associated with global amphibian declines. Our study shows that
      amphibians may be able to adjust their skin peptide defenses in response to
      stressors that are experienced early in ontogeny and that these effects extend
      through an important life-history transition. 

PMID- 24115059
TI  - An algorithm to estimate unsteady and quasi-steady pressure fields from velocity
      field measurements.
AB  - We describe and characterize a method for estimating the pressure field
      corresponding to velocity field measurements such as those obtained by using
      particle image velocimetry. The pressure gradient is estimated from a time series
      of velocity fields for unsteady calculations or from a single velocity field for
      quasi-steady calculations. The corresponding pressure field is determined based
      on median polling of several integration paths through the pressure gradient
      field in order to reduce the effect of measurement errors that accumulate along
      individual integration paths. Integration paths are restricted to the nodes of
      the measured velocity field, thereby eliminating the need for measurement
      interpolation during this step and significantly reducing the computational cost
      of the algorithm relative to previous approaches. The method is validated by
      using numerically simulated flow past a stationary, two-dimensional bluff body
      and a computational model of a three-dimensional, self-propelled anguilliform
      swimmer to study the effects of spatial and temporal resolution, domain size,
      signal-to-noise ratio and out-of-plane effects. Particle image velocimetry
      measurements of a freely swimming jellyfish medusa and a freely swimming lamprey
      are analyzed using the method to demonstrate the efficacy of the approach when
      applied to empirical data. 

PMID- 24115060
TI  - Unsteady flow affects swimming energetics in a labriform fish (Cymatogaster
      aggregata).
AB  - Unsteady water flows are common in nature, yet the swimming performance of fishes
      is typically evaluated at constant, steady speeds in the laboratory. We examined
      how cyclic changes in water flow velocity affect the swimming performance and
      energetics of a labriform swimmer, the shiner surfperch, Cymatogaster aggregata,
      during station holding. Using intermittent-flow respirometry, we measured
      critical swimming speed (Ucrit), oxygen consumption rates (O2) and pectoral fin
      use in steady flow versus unsteady flows with either low- [0.5 body lengths (BL)
      s(-1)] or high-amplitude (1.0 BL s(-1)) velocity fluctuations, with a 5 s period.
      Individuals in low-amplitude unsteady flow performed as well as fish in steady
      flow. However, swimming costs in high-amplitude unsteady flow were on average
      25.3% higher than in steady flow and 14.2% higher than estimated values obtained
      from simulations based on the non-linear relationship between swimming speed and
      oxygen consumption rate in steady flow. Time-averaged pectoral fin use (fin-beat
      frequency measured over 300 s) was similar among treatments. However, measures of
      instantaneous fin use (fin-beat period) and body movement in high-amplitude
      unsteady flow indicate that individuals with greater variation in the duration of
      their fin beats were better at holding station and consumed less oxygen than fish
      with low variation in fin-beat period. These results suggest that the costs of
      swimming in unsteady flows are context dependent in labriform swimmers, and may
      be influenced by individual differences in the ability of fishes to adjust their
      fin beats to the flow environment. 

PMID- 24115061
TI  - Compensations for increased rotational inertia during human cutting turns.
AB  - Locomotion in a complex environment is often not steady state, but unsteady
      locomotion (stability and maneuverability) is not well understood. We
      investigated the strategies used by humans to perform sidestep cutting turns when
      running. Previous studies have argued that because humans have small yaw
      rotational moments of inertia relative to body mass, deceleratory forces in the
      initial velocity direction that occur during the turning step, or 'braking'
      forces, could function to prevent body over-rotation during turns. We tested this
      hypothesis by increasing body rotational inertia and testing whether braking
      forces during stance decreased. We recorded ground reaction force and body
      kinematics from seven participants performing 45 deg sidestep cutting turns and
      straight running at five levels of body rotational inertia, with increases up to
      fourfold. Contrary to our prediction, braking forces remained consistent at
      different rotational inertias, facilitated by anticipatory changes to body
      rotational speed. Increasing inertia revealed that the opposing effects of
      several turning parameters, including rotation due to symmetrical anterior
      posterior forces, result in a system that can compensate for fourfold changes in
      rotational inertia with less than 50% changes to rotational velocity. These
      results suggest that in submaximal effort turning, legged systems may be robust
      to changes in morphological parameters, and that compensations can involve
      relatively minor adjustments between steps to change initial stance conditions. 

PMID- 24115062
TI  - An embryonic myosin converter domain influences Drosophila indirect flight muscle
      stretch activation, power generation and flight.
AB  - Stretch activation (SA) is critical to the flight ability of insects powered by
      asynchronous, indirect flight muscles (IFMs). An essential muscle protein
      component for SA and power generation is myosin. Which structural domains of
      myosin are significant for setting SA properties and power generation levels is
      poorly understood. We made use of the transgenic techniques and unique single
      muscle myosin heavy chain gene of Drosophila to test the influence of the myosin
      converter domain on IFM SA and power generation. Replacing the endogenous
      converter with an embryonic version decreased SA tension and the rate of SA
      tension generation. The alterations in SA properties and myosin kinetics from the
      converter exchange caused power generation to drop to 10% of control fiber power
      when the optimal conditions for control fibers - 1% muscle length (ML) amplitude
      and 150 Hz oscillation frequency - were applied to fibers expressing the
      embryonic converter (IFI-EC). Optimizing conditions for IFI-EC fiber power
      production, by doubling ML amplitude and decreasing oscillation frequency by 60%,
      improved power output to 60% of optimized control fiber power. IFI-EC flies
      altered their aerodynamic flight characteristics to better match optimal fiber
      power generation conditions as wing beat frequency decreased and wing stroke
      amplitude increased. This enabled flight in spite of the drastic changes to fiber
      mechanical performance.

PMID- 24115063
TI  - Pegylated leptin antagonist with strong orexigenic activity in mice is not
      effective in chickens.
AB  - A chicken gene orthologous to human leptin receptor (LEPR) has been characterized
      and found to be active in leptin signaling in vitro in response to a variety of
      recombinant leptins and leptin-containing blood samples. However, the endogenous
      ligand of chicken LEPR (cLEPR) - the putative chicken leptin - has been reported
      by us and others to be undetectable at the DNA, mRNA, protein and activity
      levels. These reports have raised questions as to cLEPR's role. Here we analyzed
      the effects of a pegylated superactive mouse leptin antagonist (PEG-SMLA) in
      chicken. We showed that the leptin antagonist efficiently and specifically blocks
      leptin signaling through the cLEPR in vitro. The effect of the leptin antagonist
      was then studied in vivo by daily administration of 10 mg kg(-1) for 10
      consecutive days to white leghorn female chickens (Gallus gallus) at the age of 2
      weeks. Despites the efficient attenuation of the cLEPR in vitro, no effect was
      observed on body mass, feed intake, feed efficiency or fat accumulation in the
      treated birds. Because similar treatment in rodents leads to a highly pronounced
      increase in appetite and body mass that are observed from the first day of
      treatment, it is concluded that the cLEPR is not implicated in the control of
      appetite or adipose homeostasis in chickens. 

PMID- 24115064
TI  - Aerobic scope does not predict the performance of a tropical eurythermal fish at
      elevated temperatures.
AB  - Climate warming is predicted to negatively impact fish populations through
      impairment of oxygen transport systems when temperatures exceed those which are
      optimal for aerobic scope (AS). This concept of oxygen- and capacity-limited
      thermal tolerance (OCLTT) is rapidly gaining popularity within climate change
      research and has been applied to several fish species. Here, we evaluated the
      relevance of aerobic performance of juvenile barramundi (Lates calcarifer) in the
      context of thermal preference and tolerance by (1) measuring standard and maximum
      metabolic rates (SMR and MMR, respectively) and AS of fish acclimated to 29
      degrees C and acutely exposed to temperatures from 23 to 38 degrees C, (2)
      allowing the fish to behaviourally select a preferred temperature between 29 and
      38 degrees C, and (3) quantifying alterations to AS after 5 weeks of acclimation
      to 29 and 38 degrees C. SMR and MMR both increased continuously with temperature
      in acutely exposed fish, but the increase was greater for MMR such that AS was
      highest at 38 degrees C, a temperature approaching the upper lethal limit (40-41
      degrees C). Despite 38 degrees C eliciting maximum AS, when given the opportunity
      the fish selected a median temperature of 31.7 +/- 0.5 degrees C and spent only
      10 +/- 3% of their time at temperatures >36 degrees C. Following acclimation to
      38 degrees C, AS measured at 38 degrees C was decreased to the same level as 29
      degrees C-acclimated fish measured at 29 degrees C, suggesting that AS may be
      dynamically modulated independent of temperature to accommodate the requirements
      of daily life. Together, these results reveal limited power of the OCLTT
      hypothesis in predicting optimal temperatures and effects of climate warming on
      juvenile barramundi.

PMID- 24115065
TI  - Self-supplementation and effects of dietary antioxidants during acute thermal
      stress.
AB  - Thermal stress leads to increased production of reactive oxygen species. If an
      organism is not able to simultaneously mount an efficient antioxidant defense
      system, this may lead to increased oxidative damage, which is potentially
      deleterious in terms of health and fitness. Exposure to cold or heat is therefore
      expected to be associated with a high demand for antioxidants. In agreement,
      several studies have shown that supplementing the diet of thermally stressed
      organisms with antioxidants leads to a reduction of oxidative damage. However,
      whether organisms can actively supplement their diet with antioxidants to
      alleviate temperature-induced oxidative damage is unknown. Here, we show that
      captive Gouldian finches (Erythrura gouldiae) supplement their diet more with
      seeds rich in antioxidants below than within their thermoneutral zone. Moreover,
      having access to seeds rich in antioxidants at temperatures below
      thermoneutrality decreases their oxidative damage. These results indicate that,
      when facing a thermal challenge, animals are able to take advantage of the
      antioxidant properties of their food to improve their oxidative balance. Having
      access to food resources rich in antioxidants may therefore be of primary
      importance for organisms in their natural habitat, as it may help them to cope
      with oxidative constraints due to challenging temperature regimes. 

PMID- 24115066
TI  - Genetics of common forms of heart disease: a long and winding road.

PMID- 24115067
TI  - Are resident c-Kit+ cardiac stem cells really all that are needed to mend a
      broken heart?

PMID- 24115068
TI  - Reactive oxygen species promote vascular smooth muscle cell proliferation.

PMID- 24115069
TI  - Recent developments in cardiovascular genetics.

PMID- 24115070
TI  - Role of NF-kappaB pathway on platelet activation.

PMID- 24115071
TI  - Reply to Schattner.

PMID- 24115072
TI  - Population pharmacokinetic and pharmacodynamic modeling of different formulations
      of ONO-5334, cathepsin K inhibitor, in Caucasian and Japanese postmenopausal
      females.
AB  - ONO-5334, a selective inhibitor of cathepsin K, is a potential new treatment for
      osteoporosis. The objectives of this study were to (1) develop population
      pharmacokinetic-pharmacodynamic (PK-PD) models for ONO-5334 using dose-ascending
      data from healthy postmenopausal females, (2) examine comparability of PK and/or
      PD profile between Caucasian and Japanese, and (3) compare PK-PD profile between
      immediate release tablet (IRT) and sustained release tablet (SRT). The population
      PK-PD models were developed for each formulation for post-dose levels of bone
      resorption markers (serum CTX and NTX). The data were provided from 4 phase 1
      studies with total of 201 Caucasian and 94 Japanese subjects. Plasma
      concentrations of ONO-5334 and bone resorption markers were thoroughly evaluated
      in those studies. An indirect response model described relationships between bone
      resorption markers and plasma concentrations of ONO-5334. There was no
      significant difference in PK and pharmacodynamic potency (IC50 ) between
      Caucasian and Japanese. Based on the developed model, serum CTX and NTX after
      administration of ONO-5334 IRT or SRT were simulated, and the results showed that
      ONO-5334 SRT would provide comparable PD effect on bone resorption markers with
      lower dose relative to IRT. 

PMID- 24115074
TI  - Clinical implications of the titer of serum hepatitis B surface antigen during
      the natural history of hepatitis B virus infection.
AB  - Although there are some differences in hepatitis B surface antigen (HBsAg) titers
      in infection with different hepatitis B virus (HBV) genotypes, the HBsAg titers
      for each HBV genotype have not been evaluated extensively. The aim of this study
      was to investigate HBsAg titers during the natural history of patients infected
      with HBV in Korea, where the HBV genotype C is endemic exclusively. Four hundred
      fifteen patients were enrolled retrospectively and classified according to
      definitions of the natural phases of HBV infection. In total, 73, 118, 147, and
      77 patients were classified in the immune tolerance, immune clearance, low
      replicative, and HBeAg-negative hepatitis phases, respectively. HBsAg titers
      (4.35 +/- 0.67, 3.74 +/- 0.68, 2.39 +/- 1.23, and 3.29 +/- 0.64 log(10)  IU/ml)
      were significantly different in the immune tolerance, immune clearance, low
      replicative, and HBeAg-negative hepatitis phases, respectively (P < 0.001). The
      ratio of HBsAg to HBV DNA was highest in the low replicative phase (1.13 +/-
      0.71, all P < 0.001) and second highest in the HBeAg-negative hepatitis phase
      (0.58 +/- 0.18, all P < 0.05). In multivariate analysis of all patients, the
      HBsAg titers did not correlate with alanine aminotransferase. However, the HBsAg
      titers correlated with age (P = 0.038), platelet count (P < 0.001) and HBV DNA (P
      < 0.001). In subgroup analysis, the HBsAg titers correlated with HBV DNA in all
      phases (P < 0.001), except for the HBeAg-negative hepatitis phase. HBsAg titers
      were significantly different across the four phases of the natural history of the
      infection and correlated significantly with HBV DNA titer in genotype C chronic
      hepatitis B patients. The HBsAg titer could be used as a biomarker to
      differentiate the natural history of HBV infection.

PMID- 24115075
TI  - What is the best imaging modality to investigate olfactory dysfunction in the
      setting of normal endoscopy?

PMID- 24115073
TI  - RANKL inhibitors induce osteonecrosis of the jaw in mice with periapical disease.
AB  - Antiresorptive medications are essential in treating diseases of pathologic
      osteoclastic bone resorption, including bone cancer and osteoporosis.
      Bisphosphonates (BPs) are the most commonly used antiresorptives in clinical
      practice. Although inhibition of bone resorption is important in regulating
      unwanted malignant and metabolic osteolysis, BP treatment is associated with
      potential side effects, including osteonecrosis of the jaws (ONJ). Recently, non
      BP antiresorptive medications targeting osteoclastic function and
      differentiation, such as denosumab, have entered the clinical arena. Denosumab
      treatment results in a similar rate of ONJ as BPs. Animal models of ONJ, using
      high-dose BP treatment in combination with tooth extraction or dental disease,
      provide valuable tools and insight in exploring ONJ pathophysiology. However, the
      ability of other antiresorptives to induce ONJ-like lesions in animal models has
      not been explored. Such studies would be beneficial in providing support for the
      role of osteoclast inhibition in ONJ pathogenesis versus a direct BP effect on
      oral tissues. Here, we tested the ability of the receptor activator of NF-kappaB
      ligand (RANKL) inhibitors RANK-Fc (composed of the extracellular domain of RANK
      fused to the fragment crystallizable [Fc] portion of immunoglobulin G [IgG]) and
      OPG-Fc (composed of the RANKL-binding domains of osteoprotegerin [OPG] linked to
      the Fc portion of IgG) to induce ONJ in mice in the presence of periapical
      disease, but in the absence of dental extractions. We demonstrate radiographic
      evidence of ONJ in RANK-Fc-treated and OPG-Fc-treated mice, including inhibition
      of bone loss, increased bone density, lamina dura thickening, and periosteal bone
      deposition. These findings closely resembled the radiographic appearance of an
      ONJ patient on denosumab treatment. Histologic examination revealed that RANK-Fc
      treatment and OPG-Fc treatment resulted in absence of osteoclasts, periosteal
      bone formation, empty osteocytic lacunae, osteonecrosis, and bone exposure. In
      conclusion, we have successfully induced ONJ in mice with periapical disease,
      using potent osteoclast inhibitors other than BPs. Our findings, coupled with ONJ
      animal models using high-dose BPs, suggest that osteoclast inhibition is pivotal
      to the pathogenesis of ONJ.

PMID- 24115076
TI  - No influence of acute RF exposure (GSM-900, GSM-1800, and UMTS) on mouse retinal
      ganglion cell responses under constant temperature conditions.
AB  - Possible non-thermal effects of radio frequency electromagnetic fields (RF-EMF)
      on retinal ganglion cells were studied in vitro under conditions of constant
      temperature. Isolated mouse retinae were exposed to GSM-900, GSM-1800, and
      universal mobile telecommunication system (UMTS) RF-EMF applying specific
      absorption rates (SAR) of 0 (sham), 0.02, 0.2, 2, and 20 W/kg. Temperature was
      kept constant within +/-0.5 to 1  degrees C for GSM-900 and +/-0.5  degrees C for
      GSM-1800 and UMTS. Responses of retinal ganglion cells to light stimuli of three
      intensities (0.5, 16, and 445 lx) were recorded before, during, and up to 35 min
      after exposure. Experiments were performed under double-blind conditions. Changes
      in light responses during and after exposure were determined for each condition
      (RF-EMF; SAR value; light intensity) with respect to the responses before
      exposure, respectively. Changes were calculated using the Euclidian distance of
      the n-dimensional response vectors, respectively. Some changes already occurred
      during sham (0 W/kg) exposure, reflecting the intrinsic variability in retinal
      ganglion cell responses. Comparison of the distance values from sham exposure
      with those from actual exposure yielded no significant differences. In addition,
      linear regression analysis of the distance values versus SAR values yielded no
      consistent dependence of light response changes. From these results we conclude
      that RF-EMF exposure at three mobile phone frequencies (GSM-900, GSM-1800, UMTS)
      and SARs up to 20 W/kg has no acute effects on retinal ganglion cell responses
      under constant temperature conditions.

PMID- 24115077
TI  - CD34-positive fibroblasts in Reinke's edema.
AB  - OBJECTIVES/HYPOTHESIS: To elucidate whether and to what extent CD34+ fibroblasts
      (so-called CD34+ fibrocytes, CD34+ dendritic cells, and CD34+ stromal cells)
      occur in normal human vocal folds and in Reinke's edema. STUDY DESIGN:
      Histological study. METHODS: Conventional, immunohistochemical, and
      ultrastructural procedures were performed in histological blocks of 18 selected
      cases of Reinke's edema (with typical findings including acellular edematous
      spaces in the subepithelial connective tissue of vocal folds, and disarrangement
      of elastic, collagen, and reticular fibers). For control purposes, four normal
      vocal folds were analyzed. RESULTS: In normal vocal folds, most stromal cells
      were spindle-shaped CD34+ fibroblasts. In Reinke's edema, increased density and
      changes in the morphology and size of this subpopulation of fibroblasts were
      demonstrated in the connective tissue surrounding the edematous spaces,
      particularly in their borders, where together with some macrophages they formed
      boundaries, mimicking the walls of distended lymphatic vessels when conventional
      stains were used. These activated CD34+ fibroblasts acquired a dendritic
      morphology (with long, moniliform, often bifurcated, overlapping multipolar
      processes), and their cytoplasmic organelles were increased in number. In
      addition to CD34, they expressed vimentin, CD10 and CD99, but no alpha-smooth
      muscle actin (alpha-SMA), CD31, CD117, CD68, h-caldesmon, desmin, or S-100
      protein. CONCLUSIONS: CD34+ fibroblasts are a major cell component in the stroma
      of vocal folds in Reinke's edema, and their activation, with increased density
      and morphologic changes around the edematous spaces, occurs without
      immunophenotypic transformation toward myofibroblasts (no expression of alpha
      SMA). The mechanisms by which these cells act in Reinke's edema require further
      study.

PMID- 24115078
TI  - Microchip electrophoresis-copper nanowires for fast and reliable determination of
      monossacharides in honey samples.
AB  - Microchip electrophoresis (ME) with electrochemical detection has been
      demonstrated to be a powerful tool in food analysis. However, the coupling of ME
      with electrochemical detection and nanotechnologies is still in its infancy,
      knowing that nanomaterials can significantly improve the ME analytical
      performance. This work reports the coupling between ME and copper nanowires
      (CuNWs) for the selective analysis of monosaccharides in honey samples. Also, in
      terms of real applicability, the study of analytical reliability of ME is an
      issue of paramount importance. To this end, a representative group of nine honey
      samples were analyzed and the results were compared with those previously
      obtained by HPLC-refractive index. ME-CuNWs approach allowed the separation of
      glucose and fructose in <250 s under optimized separation (20 mM NaOH + 10 mM H3
      BO3 , pH 12; separation voltage + 1000 V) and detection (E = +0.70 V in 20 mM
      NaOH + 10 mM H3 BO3 , pH 12) conditions. An excellent stability of EOF during
      sample analysis was achieved with RSDs for migration times <2% and for
      amperometric currents <9%. The quantitative contents for individual glucose and
      fructose obtained using ME-CuNWs in comparison with those obtained by HPLC
      refractive index were highly in agreement with errors <10% indicating the
      reliability of the approach. The excellent analytical performance obtained
      confirms the analytical potency of ME-CuNWs approach, enhancing the maturity of
      the microchip technology and opening new avenues for future implementation of
      applications in the field of food analysis. 

PMID- 24115080
TI  - Comparative study of voiding and male sexual function following open and
      laparoscopic total mesorectal excision in patients with rectal cancer.
AB  - BACKGROUND: This study aimed to compare voiding and male sexual dysfunction
      between open and laparoscopic rectal cancer surgery. METHODS: Ninety-seven
      patients (62 male and 35 female) who underwent open (n = 41) or laparoscopic (n =
      56) surgery for rectal cancer were prospectively enrolled. Urine flowmetry, the
      international prostate symptom score, and the international index of erectile
      function were assessed preoperatively and postoperatively. RESULTS: Voiding
      function score increased 1 month after surgery (open: 9.3 +/- 4.6 to 14.0 +/-
      8.2, laparoscopic: 8.3 +/- 5.3 to 12.3 +/- 5.2; P = 0.002 and P < 0.001). The
      score was even higher in both groups after 6 months, but the increases were not
      statistically significant (open: 9.9 +/- 4.5, laparoscopic: 9.2 +/- 5.6; P =
      0.546 and P = 0.280). Male patients who underwent open surgery (n = 22)
      experienced declining sexual function until 12 months post surgery (before: 55.2
      +/- 9.8, 12 months: 48.7 +/- 15.9, P = 0.031). In laparoscopic group (n = 28),
      sexual function decreased until 6 months after surgery, but rose again by 12
      months (before: 55.4 +/- 9.0, 12 months: 52.2 +/- 11.7, P = 0.134). CONCLUSIONS:
      Voiding dysfunction recovered after 6 months following both open and laparoscopic
      surgery. Male sexual function recovered more quickly in laparoscopic group and
      returned to preoperative levels after 12 months.

PMID- 24115079
TI  - IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease
      in mice.
AB  - Inflammation plays a central pathogenic role in the pernicious metabolic and end
      organ sequelae of obesity. Among these sequelae, nonalcoholic fatty liver disease
      (NAFLD) has become the most common chronic liver disease in the developed world.
      The twinned observations that obesity is associated with increased activation of
      the interleukin (IL)-17 axis and that this axis can regulate liver damage in
      diverse contexts prompted us to address the role of IL-17RA signaling in the
      progression of NAFLD. We further examined whether microbe-driven IL-17A regulated
      NAFLD development and progression. We show here that IL-17RA(-/-) mice respond to
      high-fat diet stress with significantly greater weight gain, visceral adiposity,
      and hepatic steatosis than wild-type controls. However, obesity-driven lipid
      accumulation was uncoupled from its end-organ consequences in IL-17RA(-/-) mice,
      which exhibited decreased steatohepatitis, nicotinamide adenine dinucleotide
      phosphate (NADPH)-oxidase enzyme expression, and hepatocellular damage.
      Neutralization of IL-17A significantly reduced obesity-driven hepatocellular
      damage in wild-type mice. Further, colonization of mice with segmented
      filamentous bacteria (SFB), a commensal that induces IL-17A production,
      exacerbated obesity-induced hepatocellular damage. In contrast, SFB depletion
      protected from obesity-induced hepatocellular damage. CONCLUSION: These data
      indicate that obesity-driven activation of the IL-17 axis is central to the
      development and progression of NAFLD to steatohepatitis and identify the IL-17
      pathway as a novel therapeutic target in this condition.

PMID- 24115081
TI  - Folding 19 proteins to their native state and stability of large proteins from a
      coarse-grained model.
AB  - We develop an intermediate resolution model, where the backbone is modeled with
      atomic resolution but the side chain with a single bead, by extending our
      previous model (Proteins (2013) DOI: 10.1002/prot.24269) to properly include
      proline, preproline residues and backbone rigidity. Starting from random
      configurations, the model properly folds 19 proteins (including a mutant 2A3D
      sequence) into native states containing beta sheet, alpha helix, and mixed
      alpha/beta. As a further test, the stability of H-RAS (a 169 residue protein,
      critical in many signaling pathways) is investigated: The protein is stable, with
      excellent agreement with experimental B-factors. Despite that proteins containing
      only alpha helices fold to their native state at lower backbone rigidity, and
      other limitations, which we discuss thoroughly, the model provides a reliable
      description of the dynamics as compared with all atom simulations, but does not
      constrain secondary structures as it is typically the case in more coarse-grained
      models. Further implications are described.

PMID- 24115083
TI  - Diabetes mellitus does not affect the efficacy and safety of intravesical
      onabotulinumtoxinA injection in patients with refractory detrusor overactivity.
AB  - AIMS: To investigate the efficacy and safety of intravesical onabotulinumtoxinA
      injection in patients with diabetes mellitus (DM) and refractory detrusor
      overactivity (DO). METHODS: Forty-eight type 2 DM patients with refractory DO
      received intravesical 100 U onabotulinumtoxinA injection. Another 48 age-matched
      patients were randomly selected from a non-diabetic group as controls. Video
      urodynamic studies were performed at baseline and were repeated 3 months after
      treatment. The treatment outcomes were graded on the basis of changes in the
      Patient's Perception of Bladder Condition (PPBC) and a PPBC decrease of 2 or more
      points was considered successful. Treatment-related adverse events including
      acute urinary retention, large post-voiding residual (PVR) volumes, straining to
      void, urinary tract infection, hematuria, and general weakness were recorded.
      RESULTS: The mean ages of the diabetic and non-diabetic patients were 73.1 +/-
      8.8 and 72.0 +/- 9.3 (P = 0.552), respectively. The changes of urodynamic
      parameters were comparable between the two groups. Similar successful results
      were noted at the 6-month follow-up (DM, 56% vs. non-DM, 61%, P = 0.128).
      Diabetic patients had a significantly greater incidence of large PVR volumes (DM,
      60.4% vs. non-DM, 33.3%; P = 0.007) and general weakness (DM, 10.4% vs. non-DM,
      0%; P = 0.03) after treatment. Baseline urodynamic parameters in diabetic
      patients did not predict the occurrence of adverse events. No major complication
      was noted in either group. CONCLUSIONS: Intravesical onabotulinumtoxinA injection
      is a safe and effective treatment for DM patients with refractory DO. Patients
      with DM should be informed of the increased risk of large PVR before initiation
      of treatment.

PMID- 24115082
TI  - Mechanism-based approach using a biomarker response to evaluate tocilizumab
      subcutaneous injection in patients with rheumatoid arthritis with an inadequate
      response to synthetic DMARDs (MATSURI study).
AB  - A multicenter, open-label, dose-escalation phase 1/2 study was undertaken to
      evaluate the optimal subcutaneous tocilizumab dose that would result in exposure
      comparable to the intravenous tocilizumab 8-mg/kg approved dose in patients with
      rheumatoid arthritis. A pharmacokinetic and biomarker approach was used to
      estimate the clinical optimal dose regimen of subcutaneous tocilizumab. Safety
      and efficacy of subcutaneous tocilizumab were assessed as secondary end points.
      Patients received subcutaneous tocilizumab at 81 mg every 2 weeks (q2w) (n = 8),
      162 mg q2w (n = 12), or 162 mg weekly (qw) (n = 12) for 24 weeks. 88% of 162-mg
      q2w patients and 100% of 162-mg qw patients maintained mean serum trough
      tocilizumab concentrations of >=1 ug/mL, and had exposure comparable with the
      approved intravenous tocilizumab dose of 8 mg/kg; this resulted in normalized C
      reactive protein levels and improvement in ACR20/50/70 responses. The most common
      adverse events were abnormal laboratory results, which were mild in severity.
      Anti-tocilizumab antibodies were detected in a few patients in the 81-mg q2w and
      162-mg qw groups. In conclusion, coupled with efficacy and tolerability results,
      the appropriate dose of subcutaneous tocilizumab was determined to be 162 mg q2w
      for Japanese patients. 

PMID- 24115084
TI  - The analysis of asbestos count data with "nondetects": the example of asbestos
      fiber concentrations in the lungs of brake workers.
AB  - OBJECTIVES: In the analysis of tissue for asbestos fibers, some measurements may
      be below the analytical detection limit (nondetects). The use of maximum
      likelihood and survival analysis methods have been recommended to perform
      comparisons between subjects in the presence of nondetects. When the data consist
      of "counts" another method is useful. This method is discussed, and illustrated
      with an analysis of asbestos lung burden data among brake mechanics previously
      analyzed by other methods. METHODS: Statistical models for count data, namely
      Poisson and negative binomial regression, were used to compare the asbestos fiber
      concentrations in the lungs of brake mechanics with those of control subjects.
      The fit of the models was assessed with an analysis of residuals. RESULTS: The
      negative binomial regression models fit the data well. The concentrations of
      Quebec asbestos fibers in the lungs of the brake mechanics were significantly
      higher than in the control population. CONCLUSIONS: Helsel recommended the use of
      maximum likelihood and survival analysis methods to perform comparisons in the
      presence of nondetects. When analyzing asbestos fiber count data, or other count
      data arising in occupational or environmental health, the use of models such as
      the Poisson and negative binomial may be added to the analyst's toolbox. Benefits
      are that neither of these methods requires the substitution of arbitrary values
      for the nondetects and that programs for the computation of count data models are
      contained in popular statistical software packages.

PMID- 24115085
TI  - Identification of nuclear factor-kappaB inhibitors and beta2 adrenergic receptor
      agonists in Chinese medicinal preparation Fuzilizhong pills using UPLC with
      quadrupole time-of-flight MS.
AB  - INTRODUCTION: Fuzilizhong Pills (FZLZ), a modified form of a famous traditional
      Chinese medicine (TCM) Lizhong Wan in Treatise on Febrile Diseases and consisting
      of Panax ginseng C.A.Mey. (Ren Shen), Aconitum carmichaelii Debx. (Fu Zi, Zhi),
      Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.
      (Gan Cao), Atractylodes macrocephala Koidz. (Bai Zhu) and Zingiber offcinale
      Rosc. (Gan Jiang), show strong clinical therapeutic effects for dyspnea and
      pulmonary oedema. However, the bioactive compounds are still unclear. In this
      study, FZLZ was analysed using a rapid detection method to identify its anti
      inflammatory and spasmolytic constituents. OBJECTIVE: To develop a simple
      screening method to detect the anti-inflammatory and spasmolytic constituents of
      FZLZ. METHODS: Ultra-performance liquid chromatography with quadrupole time-of
      flight mass spectrometry combined with dual-bioactive (NF-kappaB and beta2 
      adrenergic receptor) luciferase reporter assay systems was employed. RESULTS: Two
      beta2 -adrenergic receptor agonists (salsolinol and higeramine) and three
      terpenoidal analogues of NF-kappaB inhibitors such as ginsenosides derivatives,
      triperpenoids derivatives and diester-diterpenoid aconitum alkaloid derivatives
      were characterised. Mesaconitine, flaconitine, ginsenosides Rb2, Rf, Rg2, F1 and
      Ro were considered to be new NF-kappaB inhibitors. Furthermore, IL-8 detection by
      enzyme linked immunosorbent assay confirmed the anti-inflammatory effects of the
      potential NF-kappaB inhibitors. CONCLUSION: Compared with conventional
      fingerprints, activity-integrated fingerprints that contain both chemical and
      bioactive details offer a more comprehensive understanding of the chemical
      composition 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- 24115086
TI  - Synthesis and derivatization of expanded [n]radialenes (n=3, 4).
AB  - Versatile, iterative synthetic protocols to form expanded [n]radialenes have been
      developed (n=3 and 4), which allow for a variety of groups to be placed around
      the periphery of the macrocyclic framework. The successful use of the Sonogashira
      cross-coupling reaction to complete the final ring closure demonstrates the
      ability of this reaction to tolerate significant ring strain while producing
      moderate to excellent product yields. The resulting radialenes show good
      stability under normal laboratory conditions in spite of their strained, cyclic
      structures. The physical and electronic characteristics of the macrocycles have
      been documented by UV-visible spectroscopy, electrochemical methods, and X-ray
      crystallography (four derivatives), and these studies provide insight into the
      properties of these compounds as a function of pendent substitution in terms of
      conjugation and donor/acceptor functionalization. 

PMID- 24115087
TI  - Unravelling Robin sequence: considerations of diagnosis and treatment.
AB  - OBJECTIVES/HYPOTHESIS: The airway management of children with Robin sequence is
      controversial. This study provides an overview of a single-center experience with
      the diagnosis and treatment of 59 children with Robin sequence. STUDY DESIGN:
      Retrospective cohort study. METHODS: We conducted a retrospective cohort study of
      59 children (<1 year old) with Robin sequence managed between 2000 and 2010.
      Robin sequence was defined as the presence of mandibular hypoplasia and clinical
      signs of airway obstruction. Data were collected on demographic characteristics,
      the presence of a syndrome, the perinatal period, and the management of airway
      and nutritional problems. RESULTS: Eighteen children (31%) needed respiratory
      support because of severe respiratory distress, and a sleep study found
      obstructive apneas in another eight children who had been managed by prone
      positioning and/or monitoring. In the isolated group significantly fewer children
      needed respiratory support compared to the nonisolated group. After the age of 1
      year, 10% of the Robin sequence cohort was still in need of treatment for
      obstructive symptoms. Almost half (47%) needed temporary nutritional support.
      CONCLUSIONS: The prevalence of respiratory distress in children with Robin
      sequence is high. In most children, treatment with prone positioning was
      sufficient to relieve the airway obstruction. Successful treatment with prone
      positioning was significantly more often seen in children with an isolated Robin
      sequence. About one-third of all Robin sequence children needed respiratory
      support in the neonatal and/or infant period. However, in childhood, only 10% of
      the total Robin sequence cohort was still dependent on respiratory support.

PMID- 24115088
TI  - Sex- and region-specific pubertal maturation of the corticotropin-releasing
      factor receptor system in the rat.
AB  - One of the most reliable findings in psychiatry is in the incidence of anxiety
      and depression. Beginning at puberty, women develop mood disorders twice as often
      as men. Because corticotropin-releasing factor (CRF) receptors are implicated, we
      compared CRF receptor binding in pre- and postpubertal rats. In each brain area,
      CRF receptor binding was sexually dimorphic, but no two areas were alike in the
      way the sexes differed. In the nucleus accumbens and olfactory tubercle, CRF1
      binding was initially the same in juveniles, but became greater in adult females.
      In piriform cortex, CRF1 binding increased in females and decreased in males,
      again becoming sexually dimorphic. CRF1 binding in the anterior cingulate was
      greater in females than in males at both ages. In CA3, CRF1 binding was greater
      in males before puberty but decreased during puberty, abolishing the sex
      difference. CRF2 binding in the posterior bed nucleus of the stria terminalis was
      greater in males irrespective of age. In contrast, in each of three subdivisions
      of the lateral septum, females had greater CRF2 binding than males as juveniles,
      or, as juveniles and as adults. CRF2 binding in the ventromedial hypothalamus was
      the same in juveniles, but binding levels increased in males, leading to an adult
      sex difference. Thus, eight CRF receptor-expressing areas displayed eight
      distinct sex differences. These results show that sex differences pervade the CRF
      receptor system in juvenile and adult rats, and the mechanisms that control them
      are likely to be sex-, region-, and subtype-specific.

PMID- 24115089
TI  - Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell
      growth.
AB  - The deregulation of epigenetics was involved in early and subsequent carcinogenic
      events. Reversing cancer epigenetics to restore a normal epigenetic condition
      could be a rational approach for cancer treatment and specialized prevention. In
      the present study, we found that the expression levels of two epigenetic markers,
      histone H3K27 trimethylation (H3K27me3), was low but histone H3S10
      phosphorylation (pH3Ser10) was high in human bladder cancer tissues, which showed
      opposite expression patterns in their normal counterparts. Thus, we investigated
      whether a natural product, emodin, has the ability to reverse these two
      epigenetic modifications and inhibit bladder cancer cell growth. Emodin
      significantly inhibited the cell growth of four bladder cancer cell lines in a
      dose- and time-dependent manner. Emodin treatment did not induce specific cell
      cycle arrest, but it altered epigenetic modifications. Emodin treatment resulted
      in the suppression of pH3Ser10 and increased H3K27me3, contributing to gene
      silencing in bladder cancer cells. Microarray analysis demonstrated that
      oncogenic genes including fatty acid binding protein 4 (FABP4) and fibroblast
      growth factor binding protein 1 (HBP17), RGS4, tissue inhibitor of
      metalloproteinase 3 (TIMP3), WNT5b, URB, and collagen, type VIII, alpha 1
      (COL8A1) responsible for proliferation, survival, inflammation, and
      carcinogenesis were significantly repressed by emodin. The ChIP assays also
      showed that emodin increased H3K27me3 but decreased pH3Ser10 modifications on the
      promoters of repressed genes, which indicate that emodin reverses the cancer
      epigenetics towards normal epigenetic situations. In conclusion, our work
      demonstrates the significant anti-neoplastic activity of emodin on bladder cancer
      cells and elucidates the novel mechanisms of emodin-mediated epigenetic
      modulation of target genes. Our study warrants further investigation of emodin as
      an effective therapeutic or preventive agent for bladder cancer.

PMID- 24115090
TI  - The isolation of single MMX chains from solution: unravelling the assembly
      disassembly process.
AB  - Herein, we provide a systematic theoretical and experimental study of the
      structural and optical properties of MMX (M=metal, X=halide) chains. The
      influence of solvent, temperature, and concentration has been analyzed to find
      suitable parameters for initial building-block associations in solution. By using
      density functional calculations, we have computed the dissociation energy of
      different MMX oligomers (up to the tetramer) in the gas phase. On the basis of
      these findings, we discuss the most likely disassembly scenario and propose a new
      interpretation of these compounds. We also calculated the charge redistribution
      that occurs upon MM+XMMX binding in vacuum. Time-dependent density functional
      theory (TDDFT) is used to calculate the UV/visible spectra of different MMX
      chains up to the tetramer in the gas phase. The implications of these theoretical
      findings in the analysis of our experiments are discussed in the text. The
      overall body of data presented suggests a new way of looking at such linear
      structures. By taking into account these new data, we have been able to isolate
      single/few MMX chains on mica. 

PMID- 24115091
TI  - Excised larynx evaluation of wedge-shaped adjustable balloon implant for
      minimally invasive type I thyroplasty.
AB  - OBJECTIVES/HYPOTHESIS: To describe the method of inserting a wedge-shaped
      adjustable balloon implant (wABI) via a minithyrotomy for medialization
      thyroplasty and evaluate its effect on a range of phonatory parameters using the
      excised larynx bench apparatus. STUDY DESIGN: Repeated measures with each larynx
      serving as its own control. METHODS: A prototype wABI was deployed in six excised
      canine larynges of various sizes through a minithyrotomy and then filled with
      saline. Mucosal wave, aerodynamic, and acoustic parameters were measured for
      three conditions: normal, vocal fold paralysis, and paralysis with the wABI.
      RESULTS: Phonation threshold pressure (P < .001), flow (P < .001), and power (P =
      .002) were significantly lower for wABI compared to paralysis trials; values did
      not differ significantly from normal trials. Percent jitter (P = .002) and
      percent shimmer (P = .007) were also significantly decreased compared to the
      paralysis condition, and values were not significantly different compared to
      normal. The mucosal wave was preserved after insertion of the wABI. CONCLUSIONS:
      Effective vocal fold medialization with preservation of the mucosal wave was
      observed with the wABI in this preliminary excised larynx experiment. The wABI
      offers the potential for a minimally invasive insertion in addition to
      postoperative adjustability. Further studies in living animals and humans are
      warranted to evaluate clinical utility. LEVEL OF EVIDENCE: NA.

PMID- 24115093
TI  - Myofibroblasts are important contributors to human hepatocellular carcinoma:
      evidence for tumor promotion by proteome profiling.
AB  - Liver cancer typically occurs with a background of chronic fibrosis,
      characterized by the accumulation of myofibroblast-like cells. We performed 2D
      PAGE-based comparative analyses with the aim to identify proteins expressed in
      human hepatocellular carcinoma (HCC) tissue but not in neighboring healthy liver
      tissue, and to make out which cell types are responsible for the expression of
      proteins most characteristic for HCC. LC-MS/MS analysis of the most striking
      spots identified proteins that were mainly related to myofibroblast-like cells.
      To gain more insights into the role of these cells in their contribution to HCC,
      we isolated myofibroblast-like cells as well as hepatocytes, both derived from
      HCC tissues, and subjected them to proteome profiling based on shotgun
      experiments. Comparative analysis, also referring to proteome profiles of other
      cell types previously investigated by us, pointed again to a marked contribution
      of myofibroblast-like cells to HCC. Intriguingly, secretome analysis of these
      cells identified several growth factors that may act as tumor promoters and
      several proteins that have been described as potential biomarkers for HCC
      including dickkopf-1, connective tissue growth factor, and CXCL1. Other biomarker
      candidates presently identified in the secretome of myofibroblasts, including
      lipocalin-1 and pappalysin-1, may be selected for future clinical validation. The
      identification of myofibroblast-like cells as important source of tumor-promoters
      may open new avenues to therapeutic intervention by targeting these stroma cells
      in addition to the cancer cells. 

PMID- 24115092
TI  - Preclinical safety and activity of recombinant VSV-IFN-beta in an immunocompetent
      model of squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Recombinant vesicular stomatitis virus expressing interferon-beta
      (VSV-IFN-beta) has demonstrated antitumor activity in vitro and in vivo. In
      preparation for clinical testing in human squamous cell carcinoma (SCC) of the
      head and neck, we conducted preclinical studies of VSV-IFN-beta in syngeneic SCC
      models. METHODS: In vitro, VSV-IFN-beta (expressing rat or mouse interferon [IFN]
      beta)-induced cytotoxicity and propagated in rat (FAT-7) or mouse (SCC-VII) SCC
      cells during normoxia and hypoxia. In vivo, intratumoral administration of VSV
      rat-IFN-beta or VSV-human-IFN-beta in FAT-7 bearing or non-tumor bearing
      immunocompetent rats did not result in acute organ toxicity or death. RESULTS:
      VSV-r-IFN-beta replicated predominantly in tumors and a dose dependent anti-VSV
      antibody response was observed. Intratumoral or intravenous administration of VSV
      IFN-beta resulted in growth delay and improved survival compared with controls.
      CONCLUSION: The above data confirm safety and feasibility of VSV-IFN-beta
      administration in immunocompetent animals and support its clinical evaluation in
      advanced human head and neck cancer.

PMID- 24115094
TI  - Norovirus infection in immunocompromised children and children with hospital
      acquired acute gastroenteritis.
AB  - Norovirus (NoV) is a leading cause of acute viral gastroenteritis among children,
      yet its burden of disease among immunocompromised hosts and its role in hospital
      acquired infections (HAI) is not well characterized. To determine the prevalence,
      genotypes, and NoV loads among immunocompromised children and children with HAI,
      residual stool samples, and clinical data were collected at two major pediatric
      hospitals in metropolitan Atlanta from 92 children that were immunocompromised
      and/or had a hospital acquired acute gastroenteritis. NoV was identified in 16.3%
      (15/92) of all stool specimens; 23.4% (11/47) in immunocompromised only children,
      and 13.3% (4/30) in children with HAI. All NoV positive cases were genogroup II
      (GII), and GII.4 was the predominant strain followed by GII.3, GII.12, and
      GII.13. The average NoV load for immunocompromised patients was 6.3 +/- 1.4 log
      genome equivalent copies (GEC) per gram of stool compared to 5.8 +/- 1.1 log GEC
      among patients with HAI. NoV infections are common among immunocompromised
      children and children with hospital-acquired gastroenteritis, underscoring the
      urgent need for rapid NoV detection system, and highlighting the importance of
      strict hospital hygiene practices.

PMID- 24115095
TI  - Molecular basis of MAP kinase regulation.
AB  - Mitogen-activated protein kinases (MAPKs; ERK1/2, p38, JNK, and ERK5) have
      evolved to transduce environmental and developmental signals (growth factors,
      stress) into adaptive and programmed responses (differentiation, inflammation,
      apoptosis). Almost 20 years ago, it was discovered that MAPKs contain a docking
      site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence
      known as the D- or KIM-motif (kinase interaction motif). Recent crystal
      structures of MAPK:KIM-peptide complexes are leading to a precise understanding
      of how KIM sequences contribute to MAPK selectivity. In addition, new crystal and
      especially NMR studies are revealing how residues outside the canonical KIM motif
      interact with specific MAPKs and contribute further to MAPK selectivity and
      signaling pathway fidelity. In this review, we focus on these recent studies,
      with an emphasis on the use of NMR spectroscopy, isothermal titration calorimetry
      and small angle X-ray scattering to investigate these processes. 

PMID- 24115097
TI  - The Pleiotropic Effects of miRNAs on Tumor Angiogenesis.
AB  - Angiogenesis, the process of new blood vessel formation and growth from already
      existing venules is critical in vascular development and homeostasis controlled
      by the balance of pro- and anti-angiogenic factors. Emerging evidence indicates
      the development, progression, and metastasis of various human cancers are
      strongly relied on angiogenesis. However, molecular mechanisms that underlie the
      complex regulation of angiogenic processes are still not fully elucidated. Recent
      studies revealed that microRNAs (miRNAs) were important regulators of tumor
      angiogenesis and the entire research in this area has entered into a so-called
      "miRNAs era." Thus, miRNAs might be important therapeutic targets or biomarkers
      for cancer. Due to the complexity of miRNA regulating mechanisms, how specific
      miRNAs intersect with and modulate tumor angiogenesis is still unclear. The
      conflicting results of the same miRNAs from different groups indicated that
      miRNAs might possess potent activity in a cell type or cell context specific
      manner. Here, we present a summary of latest advances in understanding the roles
      of angiogenic miRNAs as potential tools or targets in cancer therapy.

PMID- 24115096
TI  - Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin
      mediated hepatitis in mice.
AB  - Prednisolone is a corticosteroid that has been used to treat inflammatory liver
      diseases such as autoimmune hepatitis and alcoholic hepatitis. However, the
      results have been controversial, and how prednisolone affects liver disease
      progression remains unknown. In the current study we examined the effect of
      prednisolone treatment on several models of liver injury, including T/NKT cell
      hepatitis induced by concanavalin A (ConA) and alpha-galactosylceramide (alpha
      GalCer), and hepatotoxin-mediated hepatitis induced by carbon tetrachloride (CCl4
      ) and/or ethanol. Prednisolone administration attenuated ConA- and alpha-GalCer
      induced hepatitis and systemic inflammatory responses. Treating mice with
      prednisolone also suppressed inflammatory responses in a model of hepatotoxin
      (CCl4 )-induced hepatitis, but surprisingly exacerbated liver injury and delayed
      liver repair. In addition, administration of prednisolone also enhanced
      acetaminophen-, ethanol-, or ethanol plus CCl4 -induced liver injury.
      Immunohistochemical and flow cytometric analyses demonstrated that prednisolone
      treatment inhibited hepatic macrophage and neutrophil infiltration in CCl4 
      induced hepatitis and suppressed their phagocytic activities in vivo and in
      vitro. Macrophage and/or neutrophil depletion aggravated CCl4 -induced liver
      injury and impeded liver regeneration. Finally, conditional disruption of
      glucocorticoid receptor in macrophages and neutrophils abolished prednisolone
      mediated exacerbation of hepatotoxin-induced liver injury. CONCLUSION:
      Prednisolone treatment prevents T/NKT cell hepatitis but exacerbates hepatotoxin
      induced liver injury by inhibiting macrophage- and neutrophil-mediated phagocytic
      and hepatic regenerative functions. These findings may not only increase our
      understanding of the steroid treatment mechanism but also help us to better
      manage steroid therapy in liver diseases.

PMID- 24115098
TI  - Is adenoidectomy alone sufficient for the treatment of airway obstruction in
      children?

PMID- 24115099
TI  - Assessing intervention efficacy on high-risk drinkers using generalized linear
      mixed models with a new class of link functions.
AB  - Unhealthy alcohol use is one of the leading causes of morbidity and mortality in
      the United States. Brief interventions with high-risk drinkers during an
      emergency department (ED) visit are of great interest due to their possible
      efficacy and low cost. In a collaborative study with patients recruited at 14
      academic ED across the United States, we examined the self-reported number of
      drinks per week by each patient following the exposure to a brief intervention.
      Count data with overdispersion have been mostly analyzed with generalized linear
      mixed models (GLMMs), of which only a limited number of link functions are
      available. Different choices of link function provide different fit and
      predictive power for a particular dataset. We propose a class of link functions
      from an alternative way to incorporate random effects in a GLMM, which
      encompasses many existing link functions as special cases. The methodology is
      naturally implemented in a Bayesian framework, with competing links selected with
      Bayesian model selection criteria such as the conditional predictive ordinate
      (CPO). In application to the ED intervention study, all models suggest that the
      intervention was effective in reducing the number of drinks, but some new models
      are found to significantly outperform the traditional model as measured by CPO.
      The validity of CPO in link selection is confirmed in a simulation study that
      shared the same characteristics as the count data from high-risk drinkers. The
      dataset and the source code for the best fitting model are available in
      Supporting Information. 

PMID- 24115100
TI  - Temporal trends in obesity, osteoporosis treatment, bone mineral density, and
      fracture rates: a population-based historical cohort study.
AB  - Diverging international trends in fracture rates have been observed, with most
      reports showing that fracture rates have stabilized or decreased in North
      American and many European populations. We studied two complementary population
      based historical cohorts from the Province of Manitoba, Canada (1996-2006) to
      determine whether declining osteoporotic fracture rates in Canada are
      attributable to trends in obesity, osteoporosis treatment, or bone mineral
      density (BMD). The Population Fracture Registry included women aged 50 years and
      older with major osteoporotic fractures, and was used to assess impact of changes
      in osteoporosis treatment. The BMD Registry included all women aged 50 years and
      older undergoing BMD tests, and was used to assess impact of changes in obesity
      and BMD. Model-based estimates of temporal changes in fracture rates (Fracture
      Registry) were calculated. Temporal changes in obesity and BMD and their
      association with fracture rates (BMD Registry) were estimated. In the Fracture
      Registry (n=27,341), fracture rates declined 1.6% per year (95% confidence
      interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6%
      to 17.4%, the decline in fractures was independent of osteoporosis treatment. In
      the BMD Registry (n=36,587), obesity increased from 12.7% to 27.4%. Femoral neck
      BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after
      covariate adjustment (p<0.001). Major osteoporotic fracture rates decreased in
      models that did not include femoral neck BMD (fully adjusted annual change -1.8%;
      95% CI, -2.9 to -0.5), but adjusting for femoral neck BMD accounted for the
      observed reduction (annual change -0.5%; 95% CI, -1.8 to +1.0). In summary, major
      osteoporotic fracture rates declined substantially and linearly from 1996 to
      2006, and this was explained by improvements in BMD rather than greater rates of
      obesity or osteoporosis treatment.

PMID- 24115101
TI  - Optimal durations of single exposures to a frequency-modulated magnetic field
      immediately after bisection in planarian predict final growth values.
AB  - Planarian (Dugesia tigrinia) were exposed to a frequency-modulated ("Thomas"),
      patterned electromagnetic field (EMF) immediately following transection through
      the pharynx. Subjects were exposed from 15 min to 3 h as well as single versus
      repeated exposures. Results from multiple experiments indicated that those
      planaria exposed from 45 to 90 min regenerated at significantly higher rates than
      those exposed less than 45 min. In addition, the study revealed that exposures
      greater than 45 min were not significantly different beyond this inflection
      point. We suggest that this particular pattern of EMF is capable of inducing
      biochemical pathways associated with cell proliferation, in particular the p38
      MAPK and hsp70 pathways.

PMID- 24115102
TI  - Development and validation of a rapid and high-sensitivity liquid chromatography
      tandem mass spectrometry assay for the determination of neostigmine in small
      volume beagle dog plasma and its application to a pharmacokinetic study.
AB  - A simple, rapid and high sensitive liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method for the determination of neostigmine in small-volume beagle dog
      plasma was developed to assess the plasma pharmacokinetics of neostigmine. After
      protein precipitation in a Sirocco 96-well filtration plate, the filtrate was
      directly injected into the LC-MS/MS system. The analytes were separated on a
      Hanbon Hedera CN column (100 * 4.6 mm, 5 um) with a mobile phase composed of
      methanol-water (60:40, v/v) and the water containing 0.01% formic acid at a flow
      rate of 0.6mL/min, with a split ratio of 1:1 flowing 300 MUL into the mass
      spectrometer. The run time was 3 min. Detection was accomplished by electrospray
      ionization source in multiple reactions monitoring mode with the precursor-to
      product ion transitions m/z 223.0 -> 72.0 and 306.0 -> 140.0 for neostigmine and
      anisodamine (internal standard), respectively. The method was sensitive with a
      lower limit of quantitation of 0.1 ng/mL, and good linearity in the range 0.1
      100ng/mL for neostigmine (r >= 0.998). All the validation data, such as accuracy,
      intra-run and inter-run precision, were within the required limits. The method
      was successfully applied to pharmacokinetic study of neostigmine methylsulfate
      injection in beagle dogs.

PMID- 24115103
TI  - A comparison of the flavor of green teas from around the world.
AB  - BACKGROUND: Green teas can be grouped based on their flavor profiles. The country
      of origin appears to have a strong influence on the flavor of green tea probably
      because similar processing methods are widely used within each particular country
      and flavor is dependent, in part, on processing. The aim of this article is to
      determine what flavor differences exist among a wide range of green teas (n =
      138) produced in various countries. RESULTS: In this study we found that roast
      processed teas were mostly responsible for brown-related flavors and steam
      processed teas were responsible for green-related flavors. The prices of the
      green teas did not differentiate the flavors of the samples. Often highly priced
      green teas were grouped with low-priced green teas from the same manufacturer or
      country of origin according to their flavor attributes. CONCLUSIONS: Differences
      in the tea plant varieties or cultivars likely affects flavors in green tea.
      However, those were not known for many samples in this research and more study
      will be needed to determine the effects of specific differences in varieties or
      cultivars.

PMID- 24115104
TI  - Laparoscopic gastrectomy for advanced gastric cancer: are the long-term results
      comparable with conventional open gastrectomy? A systematic review and meta
      analysis.
AB  - BACKGROUND AND OBJECTIVE: Laparoscopic gastrectomy (LG) for gastric cancer has
      been adopted to treat both early and locally advanced gastric cancer (AGC), but
      there are still concerns about its oncologic safety especially in AGC. The
      purpose of this meta-analysis is to compare the long-term outcomes of LG with
      those of open gastrectomy (OG) in patients with AGC. METHODS: The quantitative
      synthesis of outcomes of studies from three major databases, PubMed, Embase, and
      the Cochrane Central, was performed using common keywords related to gastric
      cancer and laparoscopy on July 31, 2012. RESULTS: Ten studies (one randomized
      controlled trial and nine retrospective cohort studies) with 1,819 participants
      (960 patients in OG, and 859 patients in LG) were included in the current meta
      analysis. Nine studies compared the overall survival rate between LG and OG for
      AGC, and five studies reported the disease-free survival. There was no
      statistical difference in overall survival (hazard ratio [HR]: 0.90, 95%
      confidence interval [CI]: 0.76-1.06, P = 0.22) and disease-free survival (HR:
      1.03, 95% CI: 0.76-1.40, P = 0.86) between the two modalities. CONCLUSIONS: The
      current clinical evidence revealed that there was no evidence that LG is inferior
      to OG even for AGC if the surgeons have sufficient experience.

PMID- 24115105
TI  - Structural and functional characterization of a novel alpha/beta hydrolase from
      cariogenic pathogen Streptococcus mutans.
AB  - The protein Smu.1393c from Streptococcus mutans is annotated as a putative
      alpha/beta hydrolase, but it has low sequence identity to the structure-known
      alpha/beta hydrolases. Here we present the crystal structure of Smu.1393c at 2.0
      A resolution. Smu.1393c has a fully open alkaline substrate pocket, whose
      conformation is unique among other similar hydrolase structures. Three residues,
      Ser101, His251, and Glu125, were identified as the active center of Smu.1393c. By
      screening a series of artificial hydrolase substrates, we demonstrated Smu.1393c
      had low carboxylesterase activity towards short-chain carboxyl esters, which
      provided a clue for exploring the in vivo function of Smu.1393c.

PMID- 24115106
TI  - Characterization of microsatellite loci and repeat density in the gooseneck
      barnacle, Pollicipes elegans, using next generation sequencing.
AB  - Pollicipes elegans is a commercially important and biogeographically significant
      rocky-shore gooseneck barnacle found along the eastern Pacific coasts of Peru, El
      Salvador, and Mexico. Little is known about its reproductive biology, and no
      genetic resources exist despite its growing importance as a fisheries species in
      the region. Next generation sequencing methods can provide rapid and cost
      effective development of molecular markers such as microsatellites, which can be
      applied to studies of paternity, parentage, and population structure in this
      understudied species. Here, we used Roche 454 pyrosequencing to develop
      microsatellite markers in P. elegans and made genomic comparisons of repeat
      density and repeat class frequency with other arthropods and more distantly
      related taxa. We identified 13 809 repeats of 1-6 bp, or a density of 9744 bp of
      repeat per megabase queried, which was intermediate in the range of taxonomic
      groups compared. Comparison of repeat class frequency distributions revealed that
      P. elegans was most similar to Drosophila melanogaster rather than the more
      closely related crustacean Daphnia pulex. We successfully isolated 15 polymorphic
      markers with an average of 9.4 alleles per locus and average observed and
      expected heterozygosities of 0.501 and 0.597, respectively. Four loci were found
      to be out of Hardy-Weinberg equilibrium, likely due to the presence of null
      alleles. A preliminary population genetic analysis revealed low but significant
      differentiation between a Peruvian (n = 47) and Mexican (n = 48) population
      (F(ST) = 0.039) and markedly reduced genetic diversity in Peru. These markers
      should facilitate future studies of paternity, parentage, and population
      structure in this species.

PMID- 24115107
TI  - Reproducibility and correlations of right ventricular end-diastolic volume index
      measured by real-time three-dimensional echocardiography.
AB  - BACKGROUND: To correlate right ventricular volumes measured by real-time three
      dimensional echocardiography (RT3DE) with left ventricular volume indices in
      patients with or without left-sided heart diseases. METHODS: For this
      retrospective, we reviewed 806 consecutive RT3DE examinations with quantitative
      evaluation of both the left and the right (RV) ventricle. We excluded cases of
      disease or surgery that would directly affect the size of the RV (eg,
      intracardiac shunt, significant tricuspid, or pulmonic regurgitation) as well as
      poor sonographic image quality, leaving a total of 701 studies for analysis. RV
      volumetric quantification was performed using dedicated software. RESULTS: Linear
      regression analysis showed that left ventricular stroke volume index
      significantly correlated with RV end-diastolic volume index (RVEDVI) (r = 0.78, p
      < 0.0001). Overall, 4% (28 of 701) of the patients had RVEDVI lower than 50
      ml/m(2) , and 12% (84 of 701) had RVEDVI greater than 100 ml/m(2) . Intraclass
      correlation coefficient ranged from 0.91 to 0.99 for intraobserver and 0.85 to
      0.98 for interobserver reproducibility. CONCLUSIONS: RT3DE was feasible and
      reproducible for quantifying RV volume. In patients without known primary RV
      pathology, RV volume strongly correlated with left ventricular stroke volume.

PMID- 24115108
TI  - Distinct stepwise reduction of a nickel-nickel-bonded compound containing an
      alpha-diimine ligand: from perpendicular to coaxial structures.
AB  - A nickel-nickel-bonded complex, [{Ni(MU-L(.-))}2] (1; L=[(2,6-iPr2C6H3)NC(Me)]2),
      was synthesized from reduction of the LNiBr2 precursor by sodium metal. Further
      controllable reduction of 1 with 1.0, 2.0 and 3.0 equiv of Na, respectively,
      afforded the singly, doubly, and triply reduced compounds [Na(DME)3].[{Ni(MU-L(.
      ))}2] (2; DME=1,2-dimethoxyethane), [Na(Et2O)]Na[(L(.-))Ni-NiL(2-)] (3), and
      [Na(Et2O)]2Na[L(2-)Ni-NiL(2-)] (4). Here L represents the neutral ligand, L(.-)
      denotes its radical monoanion, and L(2-) is the dianion. All of the four
      compounds feature a short Ni-Ni bond from 2.2957(6) to 2.4649(8) A.
      Interestingly, they display two different structures: the perpendicular (1 and 2)
      and the coaxial (3 and 4) structure, in which the metal-metal bond axis is
      perpendicular to or collinear with the axes of the alpha-diimine ligands,
      respectively. The electronic structures, Ni-Ni bonding nature, and energetic
      comparisons of the two structure types were investigated by DFT computations.

PMID- 24115109
TI  - Evaluating the predictive value of doublecortin as a marker for adult
      neurogenesis in canaries (Serinus canaria).
AB  - Doublecortin (DCX) is an important microtubule-associated protein involved in the
      migration of young neurons into the cortical layers of the brain during early
      human development. The continued expression of DCX in brain areas with protracted
      neuron recruitment has promoted this endogenous protein as a popular indirect
      tool to monitor adult neurogenesis in a variety of species. However, little is
      known about its possible involvement in other cellular processes and a thorough
      validation of DCX as a quantitative measure for neurogenesis is generally
      lacking. Here we investigated the relationship between DCX expression and neuron
      recruitment in the brains of adult canaries (Serinus canaria), a species well
      known for its adult neurogenesis. We examined the age and functional state of DCX
      labeled cells by using mitotic and neuron-specific markers, retrograde tracings,
      and immediate early gene colocalizations. Although DCX expression was high in
      brain areas implicated in adult neurogenesis, DCX-expressing neurons were also
      abundant in regions that do not recruit new neurons. Moreover, DCX expression was
      observed in adult, active neurons, differentiated projection neurons, and birth
      dated neurons of up to 1 year of age. Season and testosterone treatment affected
      DCX expression in two song control nuclei, HVC and Area X, but did not correlate
      with known patterns of neuron recruitment. Together, these results demonstrate
      that DCX expression is not exclusive to young migrating neurons, and does not
      predict neuron recruitment equally throughout the canary brain. Therefore, DCX
      labeling needs careful validation for each brain region separately in each
      species analyzed when used to quantify adult neurogenesis.

PMID- 24115110
TI  - Urinary complications and risk factors in symptomatic multiple sclerosis
      patients. Study of a cohort of 328 patients.
AB  - AIMS: Lower urinary tract dysfunctions (LUTD) are very common in Multiple
      Sclerosis (MS), have a significant social impact, while the organic impact is
      discussed. We studied urinary complications and their risk factors in our cohort
      of MS patients, in order to improve the management of LUTD in MS. METHODS:
      Between 2004 and 2009, all patients affected by MS and managed for LUTD were
      included in a retrospective study. We studied the epidemiological data (age,
      gender), the clinical data (duration of MS, EDSS score, progression of MS) and
      the paraclinical data (urinary creatinine clearance, urine culture, urinary tract
      ultrasonography and in some cases urodynamic assessment and cystography). We then
      identified the urinary complications and their risk factors. RESULTS: Three
      hundred twenty eight patients, mean age 49.9 +/- 12.3 years, with a MS for 14.3
      +/- 10 years on average and with a median EDSS score equal to 6 (1-9), were
      managed for LUTD. One hundred seventy eight (54%) patients developed one or more
      urinary complications. We identified duration of MS greater than 8.5 years and an
      EDSS above 7 as risk factors. CONCLUSION: Urinary complications are common in
      symptomatic MS, these results imply screening and specialized care to limit the
      impact on the quality of life but also to prevent urinary complications.

PMID- 24115111
TI  - UPLC-QTOF/MS for a rapid characterisation of phenolic compounds from leaves of
      Myrtus communis L.
AB  - INTRODUCTION: Although continuous research has been conducted on the biological
      activities of myrtle and the characterisation of its essential oil, few studies
      have focused on its phenolic composition despite major beneficial properties.
      OBJECTIVE: To carry out a comprehensive characterisation of infusion and
      methanolic extract from myrtle leaves by UPLC-QTOF/MS. METHODS: Myrtle-leaf
      infusions, prepared using deionised water, and the methanolic extracts were
      analysed by reversed-phase ultra-performance liquid chromatography (UPLC) coupled
      to electrospray ionisation quadrupole time-of-flight mass spectrometry
      (ESI/QTOF/MS). The MS and MS/MS experiments were conducted using the negative
      ionisation mode, in order to provide molecular-mass information and production
      spectra of the compounds for structural elucidation. RESULTS: The analytical
      method applied enabled the characterisation of several compounds such as gallic
      acid and galloyl derivatives, ellagic acid and derivatives, hexahydroxydiphenolyl
      and derivatives, flavonoids, lignans and gallomyrtucommulones. Flavonoids,
      ellagic acid and its derivatives and gallic acid and its derivatives formed the
      major fractions. CONCLUSION: UPLC combined with QTOF/MS is a powerful analytical
      method for characterising infusions and alcoholic extracts from myrtle leaves.

PMID- 24115112
TI  - A model for occupational safety and health intervention diffusion to small
      businesses.
AB  - BACKGROUND: Smaller businesses differ from their larger counterparts in having
      higher rates of occupational injuries and illnesses and fewer resources for
      preventing those losses. Intervention models developed outside the United States
      have addressed the resource deficiency issue by incorporating intermediary
      organizations such as trade associations. METHODS: This paper extends previous
      models by using exchange theory and by borrowing from the diffusion of
      innovations model. It emphasizes that occupational safety and health (OSH)
      organizations must understand as much about intermediary organizations as they do
      about small businesses. OSH organizations ("initiators") must understand how to
      position interventions and information to intermediaries as added value to their
      relationships with small businesses. Examples from experiences in two midwestern
      states are used to illustrate relationships and types of analyses implied by the
      extended model. RESULTS: The study found that intermediary organizations were
      highly attuned to providing smaller businesses with what they want, including OSH
      services. The study also found that there are opinion leader organizations and
      individual champions within intermediaries who are key to decisions and actions
      about OSH programming. CONCLUSIONS: The model places more responsibility on both
      initiators and intermediaries to develop and market interventions that will be
      valued in the competitive small business environment where the resources required
      to adopt each new business activity could always be used in other ways. The model
      is a candidate for empirical validation, and it offers some encouragement that
      the issue of sustainable OSH assistance to small businesses might be addressed.
      Am. J. Ind. Med. 56:1442-1451, 2013. Published 2013. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 24115113
TI  - Central skull base osteomyelitis: an emerging clinical entity.
AB  - OBJECTIVES/HYPOTHESIS: Skull base osteomyelitis (SBO) most commonly results as a
      complication of otitis externa in diabetic patients. Central or atypical
      presentations, unrelated to aural pathology, have been documented, though
      restricted to small patient series or case reports. The current study
      systematically analyzed the literature to construct the clinical profile of this
      rare entity. STUDY DESIGN: Systematic review of case series. METHODS: The MEDLINE
      database was searched for all published cases of central SBO. Four additional
      cases were included from the University of Texas Southwestern Medical Center.
      Statistical analysis was performed to identify trends affecting overall outcomes
      or differences in treatment. RESULTS: A total of 42 cases were included with mean
      age of 52 years and male:female ratio of 2.2:1. The most common presenting
      symptoms were headaches and cranial nerve palsies, including VI (31%), IX (29%),
      and X (29%). Staphylococcus aureus (21%) and Pseudomonas aeruginosa (19%) were
      the two most common causative pathogens. The mean duration of antimicrobial
      therapy was 21 weeks, with 55% requiring intravenous antibiotics for a mean
      duration of 6.9 weeks. Twenty of 42 patients (48%) received surgical biopsy for
      diagnosis, whereas 18 patients (43%) required adjunct surgical debridement. Women
      were more likely than men to require multiple courses of therapy (46% vs. 7%, P =
      .01). The overall mortality was 9.5%, with an additional 31% experiencing
      residual neurological dysfunction. CONCLUSIONS: Osteomyelitis of the central
      skull base poses significant challenges for timely and accurate diagnosis.
      Aggressive management with antimicrobials, coupled with surgical debridement in
      select cases, may avoid serious neurologic morbidity and mortality.

PMID- 24115114
TI  - Genome-wide screening of aberrant DNA methylation which associated with gene
      expression in mouse skin cancers.
AB  - Epigenetic alteration of genomic DNA is a common and key process in
      carcinogenesis. There is considerable evidence indicating that some of the
      somatic alterations occurring during carcinogenesis in humans also involve the
      same processes as those observed in mice. Therefore, we analyzed mouse skin
      cancer tissues induced by the 2-stage carcinogenesis model to identify skin tumor
      specific differentially methylated regions (ST-DMRs) during the multistep
      carcinogenesis process. We have previously identified ST-DMRs using the
      restriction landmark genomic scanning (RLGS) technique and reported that some of
      the mouse ST-DMRs were also epigenetically modified in human cancers, such as
      melanoma, neuroblastoma, and brain tumor. These results encouraged us to pursue
      global methylation screening in mouse skin carcinogenesis. Using the methylated
      DNA immunoprecipitation (MeDIP) method combined with the NimbleGen promoter plus
      CpG island (CpGi) array, we identified 615 ST-DMRs. In combination with global
      gene expression analysis, 91 of these ST-DMRs were shown to be located on or
      around the genes differentially expressed between normal skin and tumor tissues,
      including a candidate human tumor suppressor gene Tfap2e. As observed in human
      colorectal cancers, Tfap2e was methylated at a CpGi located in intron 3 and
      downregulated in skin tumors. Our results identified aberrant methylated regions
      that were associated with gene expression regulation during carcinogenesis, which
      may indicate critical genetic regions also involved in human carcinogenesis. (c)
      2013 Wiley Periodicals, Inc. 

PMID- 24115115
TI  - Long-term functional and quality of life evaluation after treatment for advanced
      pharyngolaryngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to compare total laryngectomy versus
      concurrent chemoradiotherapy (CRT) for functional and long-term quality of life
      (QOL) outcomes in patients with pharyngolaryngeal carcinoma. METHODS: Among 145
      patients treated for advanced pharyngolaryngeal cancer by CRT or total
      laryngectomy between 2000 and 2008, 47 patients who had completed treatment for
      >1 year and were determined to be disease-free were evaluated for function and
      QOL using the European Organization for Research and Treatment of Cancer Quality
      of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30). RESULTS: No significant
      difference was observed between the total laryngectomy group (26 patients) and
      the CRT group (21 patients) concerning feeding tube (p = .72), oral supplements
      (p = .84), and pneumonia (p = 1.00). Laryngeal functional rate after CRT was 72%
      at 2 years. No significant difference was observed between the 2 groups when
      using EORTC-QLQ-C30 scales (p > .05). According to the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and
      Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaire, surgical patients reported
      significantly greater difficulties with smell and taste (p = .005) and
      chemoradiation patients with dry mouth (p = .010) and weight loss (p = .022).
      Differences that seemed clinically meaningful but not statistically significant
      emerged on several other scales. CONCLUSION: Both total laryngectomy and CRT led
      to a similar high rate of dysphagia-related morbidity (feeding tube, oral
      supplements, and pneumonia) and QOL alteration, but the groups differed in the
      specific QOL domains affected.

PMID- 24115116
TI  - Nickel hydroxide nanoparticle activated semi-metallic TiO(2) nanotube arrays for
      non-enzymatic glucose sensing.
AB  - Semi-metallic TiO2 nanotube arrays (TiOx Cy NTs) have been decorated uniformly
      with Ni(OH)2 nanoparticles without the aid of a polymer binder. The resulting
      hybrid nanotube arrays exhibit excellent catalytic activity towards non-enzymatic
      glucose electro-oxidation. The anodic current density of the glucose oxidation is
      significantly improved compared with traditional TiO2 nanotubes decorated with
      Ni(OH)2 . Moreover, the Ni(OH)2 /TiOx Cy NT-based electrode shows a fast
      response, high sensitivity, wide linear range, good selectivity and stability
      towards glucose electro-oxidation, and thus provides a promising and cost
      effective sensing platform for non-enzymatic glucose detection. 

PMID- 24115117
TI  - Molecular characterization of norovirus variants and genetic diversity of
      noroviruses and sapoviruses in Thailand.
AB  - Norovirus (NoV) and Sapovirus (SaV) have been reported as a common cause of acute
      gastroenteritis worldwide. For a decade, surveillances of NoV and SaV have been
      conducted continually in Thailand. To monitor the epidemiological situation and
      to determine the genetic variation of NoV and SaV in Chiang Mai, Thailand, 567
      samples collected from pediatric patients hospitalized with acute gastroenteritis
      were examined during 2007, and 2010-2011 by semi-nested RT-PCR and nucleotide
      sequencing methods. NoV was detected at 15.9%. Phylogenetic analysis revealed
      multiple NoV genotypes, GI/14 (1.1%), GII/1 (1.1%), GII/2 (1.1%), GII/3 (4.4%),
      GII/4 (65.6%), GII/6 (10.0%), GII/7 (2.2%), GII/12 (4.4%), GII/13 (3.3%), GII/16
      (5.7%), and unclassified genotype (1.1%), circulating in this area. Among these,
      NoV GII/4 was the most prevalent genotype with a predominance of GII/4 2009 over
      other variants, 1996, 2006a, and 2006b. For SaV, the prevalence was 1.2% which
      was much lower than those of NoV and only SaV GI/1 was detected. This study
      highlights the epidemiology of NoV and SaV and genetic diversity of viruses
      circulating in pediatric patients hospitalized with acute gastroenteritis in
      Chiang Mai, Thailand.

PMID- 24115118
TI  - Observation versus neck dissection for positron-emission tomography-negative
      lymphadenopathy after chemoradiotherapy.
AB  - OBJECTIVES/HYPOTHESIS: To analyze outcomes among patients with residual positron
      emission tomography (PET)-negative lymphadenopathy after chemoradiotherapy for
      head and neck cancer based on whether or not they underwent neck dissection.
      STUDY DESIGN: Retrospective review. METHODS: Fifty-five patients with stage
      III/IV squamous cell carcinoma of the head and neck were identified with residual
      PET-negative lymphadenopathy based on standardized uptake value of <3. All
      patients had been treated with chemoradiotherapy to a median dose of 70 Gy
      (range, 60-4 Gy). RESULTS: With a median follow-up of 30 months (range, 6-67
      months), the 3-year overall survival (85% vs. 81%, P = .57), progression-free
      survival (88% vs. 88%, P = .42), and local-regional control (96% vs. 100%, P =
      .68), did not differ between patients treated by neck dissection or observation.
      CONCLUSIONS: Omission of neck dissection appears to be reasonable for patients
      with residual lymphadenopathy but negative PET after chemoradiotherapy for head
      and neck cancer. LEVEL OF EVIDENCE: 4.

PMID- 24115120
TI  - Fate and transport of halogenated persistent, bioaccumulative, and toxic
      chemicals: we've come a long way, baby.

PMID- 24115119
TI  - Probing impact of active site residue mutations on stability and activity of
      Neisseria polysaccharea amylosucrase.
AB  - The amylosucrase from Neisseria polysaccharea is a transglucosidase from the GH13
      family of glycoside-hydrolases that naturally catalyzes the synthesis of alpha
      glucans from the widely available donor sucrose. Interestingly, natural molecular
      evolution has modeled a dense hydrogen bond network at subsite -1 responsible for
      the specific recognition of sucrose and conversely, it has loosened interactions
      at the subsite +1 creating a highly promiscuous subsite +1. The residues forming
      these subsites are considered to be likely involved in the activity as well as
      the overall stability of the enzyme. To assess their role, a structure-based
      approach was followed to reshape the subsite -1. A strategy based on stability
      change predictions, using the FoldX algorithm, was considered to identify the
      best candidates for site-directed mutagenesis and guide the construction of a
      small targeted library. A miniaturized purification protocol was developed and
      both mutant stability and substrate promiscuity were explored. A range of 8 
      degrees C between extreme melting temperature values was observed and some
      variants were able to synthesize series of oligosaccharides with distributions
      differing from that of the parental enzyme. The crucial role of subsite -1 was
      thus highlighted and the biocatalysts generated can now be considered as starting
      points for further engineering purposes.

PMID- 24115121
TI  - Progress toward understanding the bioaccumulation of perfluorinated alkyl acids.

PMID- 24115122
TI  - Predicted transport of pyrethroid insecticides from an urban landscape to surface
      water.
AB  - The authors developed a simple screening-level model of exposure of aquatic
      species to pyrethroid insecticides for the lower American River watershed
      (California, USA). The model incorporated both empirically derived washoff
      functions based on existing, small-scale precipitation simulations and empirical
      data on pyrethroid insecticide use and watershed properties for Sacramento
      County, California, USA. The authors calibrated the model to in-stream monitoring
      data and used it to predict daily river pyrethroid concentration from 1995
      through 2010. The model predicted a marked increase in pyrethroid toxic units
      starting in 2000, coincident with an observed watershed-wide increase in
      pyrethroid use. After 2000, approximately 70% of the predicted total toxic unit
      exposure in the watershed was associated with the pyrethroids bifenthrin and
      cyfluthrin. Pyrethroid applications for aboveground structural pest control on
      the basis of suspension concentrate categorized product formulations accounted
      for greater than 97% of the predicted total toxic unit exposure. Projected
      application of mitigation strategies, such as curtailment of structural perimeter
      band and barrier treatments as recently adopted by the California Department of
      Pesticide Regulation, reduced predicted total toxic unit exposure by 84%. The
      model also predicted that similar reductions in surface-water concentrations of
      pyrethroids could be achieved through a switch from suspension concentrate
      categorized products to emulsifiable concentrate-categorized products without
      restrictions on current-use practice. Even with these mitigation actions, the
      predicted concentration of some pyrethroids would continue to exceed chronic
      aquatic life criteria.

PMID- 24115123
TI  - Pesticides in blood from spectacled caiman (Caiman crocodilus) downstream of
      banana plantations in Costa Rica.
AB  - Spectacled caiman (Caiman crocodilus) are fish-eating crocodilians that inhabit
      freshwater habitat in tropical regions of the Americas. To assess the exposure of
      caiman to pesticides from banana plantations, the authors collected whole blood
      samples (30 mL) from 14 adult caiman that were captured in the North Atlantic
      region of Costa Rica. Blood samples were analyzed for 70 legacy- and current-use
      pesticides and breakdown products using newly developed ultra-trace, high
      resolution mass spectrometry (HRMS). Caiman accumulated pesticides ranked by
      concentration as dieldrin > permethrin > mirex > 4,4'-DDE > alpha-endosulfan >
      heptachlor epoxide > oxychlordane > heptachlor > cypermethrin. Caiman within the
      high-intensity banana crop watershed of Rio Suerte had higher pesticide burdens
      relative to other more remote locations (F = 12.79; p = 0.00). Pesticide
      concentration decreased with distance from upstream banana plantations in this
      river system (F = 20.76; p = 0.00). Caiman body condition was negatively
      correlated with total pesticide concentrations (F = 6.23; p = 0.02) and with
      proximity to banana plantations (F = 5.05; p = 0.04). This suggests that either
      pesticides elicited toxic effects in caiman, resulting in diminished overall
      health, or that the quantity or quality of their prey was reduced by pesticides
      downstream of plantation waterways. The authors' results indicate that pesticide
      use in banana plantations is impacting a high trophic level species inhabiting
      one of the most important wilderness areas in Costa Rica (Tortuguero National
      Park).

PMID- 24115124
TI  - Effects of selenium on development, survival, and accumulation in the honeybee
      (Apis mellifera L.).
AB  - Apis mellifera L. (Hymenoptera: Apidae) is an important agricultural pollinator
      in the United States and throughout the world. In areas of selenium (Se)
      contamination, honeybees may be at risk because of the biotransfer of Se from
      plant products such as nectar and pollen. Several forms of Se can occur in
      accumulating plants. In the present study, the toxicity of 4 compounds (selenate,
      selenite, methylselenocysteine, and selenocystine) to honeybee adult foragers and
      larvae was assessed using dose-response bioassays. Inorganic forms were more
      toxic than organic forms for both larvae (lethal concentration [LC50] selenate =
      0.72 mg L(-1) , LC50 selenite = 1.0 mg L(-1) , LC50 methylselenocysteine = 4.7 mg
      L(-1) , LC50 selenocystine = 4.4 mg L(-1) ) and foragers (LC50 selenate = 58 mg
      L(-1) , LC50 selenite = 58 mg L(-1) , LC50 methylselenocysteine = 161 mg L(-1) ,
      LC50 selenocystine = 148 mg L(-1) ). Inorganic forms of Se caused rapid
      mortality, and organic forms had sublethal effects on development. Larvae
      accumulated substantial amounts of Se only at the highest doses, whereas foragers
      accumulated large quantities at all doses. The present study documented very low
      larval LC50 values for Se; even modest transfer to brood will likely cause
      increased development times and mortality. The toxicities of the various forms of
      Se to honeybee larvae and foragers are discussed in comparison with other insect
      herbivores and detritivores.

PMID- 24115125
TI  - Crystal structure of Mycobacterium tuberculosis CarD, an essential RNA polymerase
      binding protein, reveals a quasidomain-swapped dimeric structural architecture.
AB  - Mycobacterium tuberculosis (Mtb) CarD is an essential transcriptional regulator
      that binds RNA polymerase and plays an important role in reprogramming
      transcription machinery under diverse stress conditions. Here, we report the
      crystal structure of CarD at 2.3 A resolution, that represents the first
      structural description of CarD/CdnL-Like family of proteins. CarD adopts an
      overall bi-lobed structural architecture where N-terminal domain resembles 'tudor
      like' domain and C-terminal domain adopts a novel five helical fold that lacks
      the predicted leucine zipper structural motif. The structure reveals dimeric
      state of CarD resulting from beta-strand swapping between the N-terminal domains
      of each individual subunits. The structure provides crucial insights into the
      possible mode(s) of CarD/RNAP interactions.

PMID- 24115126
TI  - Sensitive determination of positional isomers of benzenediols in human urine by
      boronate affinity capillary electrophoresis with chemiluminescence detection.
AB  - A boronate ACE coupled with chemiluminescence (CL) detection was developed for
      sensitive determination of three isomeric benzenediols, which was based on the
      principle of an inhibited effect of borate complexation on the CL reaction
      between luminol and potassium hexacyanoferrate (K3 Fe(CN)6 ) in alkaline
      solution. The effects of some important factors on CE separation and CL intensity
      were systemically investigated. Baseline separation of isomeric benzenediols
      including o-benzenediol, m-benzenediol, and p-benzenediol was achieved by using a
      mobile phase of 40 mmol/L glycine-NaOH buffer at pH 9.4 containing 0.8 mmol/L
      luminol and 0.4 mol/L 4-iodophenylboronic acid. The calibration curves of the
      analytes by plotting the peak height against corresponding concentration were
      linear over the range of 4.5 * 10(-8) ~ 4.5 * 10(-5) mol/L for p-benzenediol, 6.8
      * 10(-8) ~ 2.7 * 10(-5) mol/L for m-benzenediol, and 9.0 * 10(-8) ~ 4.5 * 10(-5)
      mol/L for o-benzenediol. The corresponding detection limits for p-, m-, and o
      benzenediols were 2.8 * 10(-8) mol/L (68 amol), 3.2 * 10(-8) mol/L (108.4 amol),
      and 3.7 * 10(-8) mol/L (125.8 amol; S/N = 3), respectively. The proposed method
      has been successfully applied to the analysis of trace benzenediols in spiked
      human urine sample and the recoveries were >97.2%. Our primary result
      demonstrated the proposed CE-CL method has great potential for biomarker
      determination in clinical diagnosis.

PMID- 24115127
TI  - Interarytenoid botulinum toxin injection for recalcitrant vocal process
      granuloma.
AB  - OBJECTIVES/HYPOTHESIS: This study evaluated the efficacy of botulinum toxin type
      A injected into the interarytenoid muscle to treat recalcitrant vocal process
      granulomas. STUDY DESIGN: Retrospective clinical review at a tertiary care
      center. METHODS: Eight patients with vocal process granulomas refractory to a
      variety of prior treatments including surgical resection, proton pump inhibitor
      therapy, and voice therapy underwent percutaneous injection of botulinum toxin
      type A into the interarytenoid muscle, performed in an office setting. Doses
      ranged from 5 U to 25 U in one to two injections. RESULTS: One patient
      demonstrated no improvement, two patients demonstrated partial resolution, and
      five patients demonstrated complete resolution of their granulomas. Four patients
      noted transient breathiness. There were no other side effects. All patients
      tolerated the injections without difficulty. CONCLUSION: Botulinum toxin
      injection into the interarytenoid muscle appears to be a safe and effective
      modality for treating recalcitrant vocal process granuloma.

PMID- 24115128
TI  - Adaptive immune responses triggered by oxidative stress contribute to hepatic
      inflammation in NASH.
AB  - Previous studies have shown that human nonalcoholic steatohepatitis (NASH) is
      often associated with the presence of circulating antibodies against protein
      adducted by lipid peroxidation products. Here we used the methionine-choline
      deficient (MCD) model of NASH to characterize the possible involvement of
      adaptive immunity in NASH. In mice fed up to 8 weeks with the MCD diet the
      extension of liver injury and lobular inflammation paralleled the development of
      immunoglobulin G (IgG) against malonyldialdehyde (MDA) and 4-hydroxynonenal (4
      HNE)-derived antigens as well as with the hepatic recruitment of CD4(+) and
      CD8(+) T-lymphocytes responsive to the same antigens. Moreover, in these animals
      the individual IgG reactivity against MDA-adducts positively correlated with
      transaminase release and hepatic tumor necrosis factor alpha (TNF-alpha)
      expression. To substantiate the role of immune responses triggered by oxidative
      stress in the progression of NASH, mice were immunized with MDA-adducted bovine
      serum albumin (MDA-BSA) before feeding the MCD diet. MDA-BSA immunization did not
      affect control mice livers, but further stimulated transaminase release, lobular
      inflammation, and the hepatic expression of proinflammatory cytokine in MCD-fed
      mice. The increased severity of NASH in immunized MCD-fed mice involved liver
      recruitment and the T helper (Th)-1 activation of CD4(+) T cells that, in turn,
      further stimulated macrophage M1 responses. Moreover, hepatic fibrosis was also
      evident in these animals in relation with an IL-15-mediated increase of natural
      killer T-cells (NKT) and the up-regulation in liver production of osteopontin by
      NKT cells and hepatic macrophages. CONCLUSION: These results indicate that
      oxidative stress can contribute to the progression of NASH by stimulating both
      humoral and cellular immune responses, pointing to the possible role of adaptive
      immunity in the pathogenesis of the disease.

PMID- 24115129
TI  - Risedronate slows or partly reverses cortical and trabecular microarchitectural
      deterioration in postmenopausal women.
AB  - During early menopause, steady-state bone remodeling is perturbed; the number of
      basic multicellular units (BMUs) excavating cavities upon the endosteal surface
      exceeds the number (generated before menopause) concurrently refilling. Later in
      menopause, steady-state is restored; the many BMUs generated in early menopause
      refill as similarly large numbers of BMUs concurrently excavate new cavities. We
      hypothesized that risedronate reduces the number of cavities excavated. However,
      in younger postmenopausal women, the fewer cavities excavated will still exceed
      the fewer BMUs now refilling, so net porosity increases, but less than in
      controls. In older postmenopausal women, the fewer cavities excavated during
      treatment will be less than the many (generated during early menopause) now
      refilling, so net porosity decreases and trabecular volumetric bone mineral
      density (vBMD) increases. We recruited 324 postmenopausal women in two similarly
      designed double-blind placebo-controlled studies that included 161 younger (Group
      1, <= 55 years) and 163 older (Group 2, >= 55 years) women randomized 2:1 to
      risedronate 35 mg/week or placebo. High-resolution peripheral computed tomography
      was used to image the distal radius and tibia. Cortical porosity was quantified
      using the StrAx1.0 software. Risedronate reduced serum carboxyterminal cross
      linking telopeptide of type 1 bone collagen (CTX-1) and serum amino-terminal
      propeptide of type 1 procollagen (P1NP) by ~50%. In the younger group, distal
      radius compact-appearing cortex porosity increased by 4.2% +/- 1.6% (p = 0.01) in
      controls. This was prevented by risedronate. Trabecular vBMD decreased by 3.6% +/
      1.4% (p = 0.02) in controls and decreased by 1.6% +/- 0.6% (p = 0.005) in the
      risedronate-treated group. In the older group, changes did not achieve
      significance apart from a reduction in compact-appearing cortex porosity in the
      risedronate-treated group (0.9% +/- 0.4%, p = 0.047). No between-group
      differences reached significance. Results were comparable at the distal tibia.
      Between-group differences were significant for compact-appearing cortex porosity
      (p = 0.005). Risedronate slows microstructural deterioration in younger and
      partly reverses it in older postmenopausal women, features likely to contribute
      to antifracture efficacy.

PMID- 24115130
TI  - Patient-based outcomes of in-office KTP ablation of vocal fold polyps.
AB  - OBJECTIVES/HYPOTHESIS: Recent data have suggested that in-office potassium
      titanyl phosphate (KTP) laser treatment for benign vocal fold lesions yields
      significant reduction in lesion size with favorable effects on both mucosal wave
      and glottic closure. However, these previous studies omitted voice-related
      outcomes. We sought to compliment these previous data with voice-related outcomes
      in a cohort of patients undergoing KTP ablation of vocal fold polyps. STUDY
      DESIGN: Retrospective outcomes study. METHODS: Voice Handicap Index (VHI)-10 and
      acoustic measures were reviewed for 31 consecutive patients with benign vocal
      fold polyps treated with in-office KTP laser surgery. All data were analyzed
      statistically via a mixed model fit to analyze the data from each of three
      clinical visits. RESULTS: Across all patients, the mean VHI-10 scores decreased
      at first follow-up from 19.7 to 9.7 (P < .0001). At subsequent follow-up visits,
      the VHI-10 scores remained stable (mean, 8.3). This shift in VHI scores was
      accompanied by favorable improvements in both noise-to-harmonic ratio and
      speaking fundamental frequency in both males and females. CONCLUSIONS: In-office
      KTP ablation of vocal fold polyps had a favorable effect on patient-reported
      handicap as determined by the VHI-10. This treatment also slightly altered
      physiologic measures of voice; however, these measures did not achieve
      statistical significance.

PMID- 24115131
TI  - Role of endolaryngeal surgery (with or without laser) versus radiotherapy in the
      management of early (T1) glottic cancer: a systematic review.
AB  - BACKGROUND: Treatment options for early glottic cancer include transoral
      microsurgery or radiotherapy (RT). There is continuing debate about which is the
      superior treatment. METHODS: The literature was searched from 1996 to 2011 using
      MEDLINE, EMBASE, and Cochrane Library. A quality assessment of each included
      study was conducted and reported. RESULTS: There is no evidence in favor of 1
      treatment modality when considering likelihood of local control or overall
      survival. There is a suggestion that RT may be associated with less measureable
      perturbation of voice as compared to surgery, but no significant differences were
      seen in patient perception. The likelihood of laryngeal preservation may be
      higher when surgery can be offered as initial treatment. CONCLUSION: For patients
      with early (T1) glottic cancer, treatment options include the equally effective
      endolaryngeal surgery, with or without laser, or radiation therapy. The choice
      between treatment modalities should be based on patient and clinician preferences
      and general medical condition.

PMID- 24115132
TI  - Implantable and ingestible medical devices with wireless telemetry
      functionalities: a review of current status and challenges.
AB  - Wireless medical telemetry permits the measurement of physiological signals at a
      distance through wireless technologies. One of the latest applications is in the
      field of implantable and ingestible medical devices (IIMDs) with integrated
      antennas for wireless radiofrequency (RF) communication (telemetry) with exterior
      monitoring/control equipment. Implantable medical devices (MDs) perform an
      expanding variety of diagnostic and therapeutic functions, while ingestible MDs
      receive significant attention in gastrointestinal endoscopy. Design of such
      wireless IIMD telemetry systems is highly intriguing and deals with issues
      related to: operation frequency selection, electronics and powering, antenna
      design and performance, and modeling of the wireless channel. In this paper, we
      attempt to comparatively review the current status and challenges of IIMDs with
      wireless telemetry functionalities. Full solutions of commercial IIMDs are also
      recorded. The objective is to provide a comprehensive reference for scientists
      and developers in the field, while indicating directions for future research.

PMID- 24115133
TI  - Telesonography: virtual 3D image processing of remotely acquired abdominal,
      vascular, and fetal sonograms.
AB  - PURPOSE: To design and test a new telesonography technique using remote volume
      acquisition by untrained operators in locations without access to trained
      sonographers, postprocessing, and interpretation done at expert centers.
      MATERIALS AND METHODS: The technique was tested with 84 sonograms of organs
      acquired in pregnant women (n = 8) and patients with various abdominal pathologic
      conditions (n = 11) located in French Guyana (France), Ceuta (Spain), and
      Murighiol (Romania). An operator inexperienced in sonography (US) placed the
      transducer over the predetermined acoustic window for each organ, then swept it
      from a -45 degrees  to a +45 degrees  position to scan the targeted organ. The
      acquired volume dataset was sent to an expert center via the Internet and
      reconstructed using a proprietary software, which allowed a trained sonographer
      to navigate through the appropriately reconstructed sonograms. RESULTS: After
      three-dimensional processing at the expert center, the organs scanned in the
      obstetrical cases were adequately visualized by the expert in seven of eight
      (88%) examinations of the fetal head, femur, and umbilical cord and eight of
      eight (100%) examinations of the fetal abdomen and placenta, whereas in the
      general abdominal cases, the liver, gallbladder, portal vein, and right kidney
      were correctly visualized in 10 of 11 (91%) examinations. CONCLUSIONS:
      Telesonography allowed untrained operators to scan and transfer the US volume
      datasets over the Internet to an expert center where an expert sonographer could
      navigate through the reconstructed US volume and visualize sonograms of
      diagnostic quality.

PMID- 24115134
TI  - Optimisation of enzymatic synthesis of cocoa butter equivalent from high oleic
      sunflower oil.
AB  - BACKGROUND: High oleic sunflower oil (HOSO) and a fatty acid (FA) mixture were
      inter-esterified in a solvent-free system catalysed by Lipozyme RM IM to produce
      a cocoa butter equivalent (CBE). The effects of reaction conditions on the
      percentage of saturate-oleoyl-saturate (SOS) and saturate-saturate-oleoyl (SSO)
      triacylglycerols (TAGs) were studied. The process was further optimised by
      response surface methodology. A five-factor response surface design was used to
      investigate the influences of the five major factors and their mutual
      relationships. The five factors were substrate ratio (A, FA/HOSO, mol mol-1),
      enzyme load (B, wt% based on substrates), water content (C, wt% based on
      substrates), reaction temperature (D, degrees C) and reaction time (E, in hours)
      varying at three levels together with two star point levels. RESULTS: The highest
      yield (59.1% SOS) and lowest acyl migration (2.9% SSO) was obtained at 10% enzyme
      load, 1% water content, 1:7 substrate mole ratio, 65 degrees C reaction
      temperature and 6 h reaction time. All the investigated factors except substrate
      ratio had significant effect on acyl migration. CONCLUSION: The quadratic
      response models sufficiently described the acidolysis reaction. All parameters
      had significant effect on the percentage of SOS TAGs. Based on the models, the
      reaction was optimised to obtain a maximum yield of SOS TAGs.

PMID- 24115135
TI  - More on lot-to-lot changes.

PMID- 24115136
TI  - The global need to define normality: the 99th percentile value of cardiac
      troponin.
AB  - BACKGROUND: How to select a presumably normal population for the establishment of
      99th percentile cutoffs for cardiac troponin assays has not been adequately
      addressed. Lack of attention to this question can result in misleading medical
      decision cutoffs. CONTENT: From our review of the peer-reviewed literature,
      including international recommendations, no uniform procedure is followed and no
      uniform guideline has been published by experts or regulatory agencies to guide
      researchers or manufacturers of cardiac troponin assays in their quest to define
      the health or "normality" of a reference population that is used to establish an
      accurate 99th percentile value. As we progress globally into the era of high
      sensitivity cardiac troponin assays, we propose several suggested approaches to
      define presumably normal individuals by use of clinical and biomarker surrogates.
      SUMMARY: Our uniform approach to defining who is normal and who may not be normal
      will help to define diagnostic and risk outcomes assessments in the management of
      patients with suspected myocardial injury, both for use in current clinical
      practice and clinical research, as well as for the potential future use of
      cardiac troponin in primary prevention.

PMID- 24115137
TI  - Harmonization of test results: what are the challenges; how can we make it
      better?

PMID- 24115138
TI  - Vitamin D supplementation after parathyroidectomy: effect on bone mineral density
      a randomized double-blind study.
AB  - Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower
      bone mineral density (BMD), and an increased risk of fractures. They also have a
      high incidence of low vitamin D levels (25-OH-vitamin D <50 nmol/L) that could
      worsen the negative effect on the bone. In this double-blinded clinical trial,
      150 patients with PHPT were randomized, after successful parathyroidectomy (PTX),
      to 1-year daily treatment with either cholecalciferol 1600 IU and calcium
      carbonate 1000 mg (D+) or calcium carbonate alone (D-). BMD was measured in the
      lumbar spine, femoral neck, total hip, distal and 33% radius using dual-energy X
      ray absorptiometry (DXA) before surgery and after 1 year of study medication.
      Median age was 60 (range 30-80) years and there were 119 (79%) women and 31 (21%)
      men; 76% had 25-OH-D <50 nmol/L before PTX and 50% had persistent elevated
      parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the
      lumbar spine, femoral neck, and total hip was observed in both groups (D+ : 3.6%,
      3.2%, and 2.7%, p<0.001, respectively; and D-: 3.0%, 2.3%, and 2.1%,
      respectively, p<0.001). Patients with vitamin D supplementation also increased
      their BMD in distal radius (median 2.0%; interquartile range, -1.7% to 5.4%;
      p=0.013). The changes in BMD, especially in the hips, were correlated to the
      baseline concentrations of PTH, ionized calcium, and bone markers (p<0.001). A
      benefit from vitamin D substitution was observed among patients with a persistent
      postoperative PTH elevation, who also improved their BMD at 33% radius and radius
      ultradistal (p<0.05). In conclusion, except for a minor improvement of radius
      BMD, our data show no beneficial effect on BMD or bone turnover markers of
      vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest
      association with improvement in BMD.

PMID- 24115139
TI  - Neuropsychologist experts and neurolaw: cases, controversies, and admissibility
      challenges.
AB  - Clinical neuropsychologists engage increasingly in forensic consulting activities
      because such expert opinions are generally relevant, reliable and helpful in
      resolving certain legal claims, especially those related to traumatic brain
      injury. Consequently, practitioners of law, medicine and psychology would benefit
      from understanding the nature of neuropsychological evidence, the standards for
      its admissibility, and its expanding role in neurolaw. This article reviews
      important evidentiary rules regulating relevance, preliminary questions, and
      expert testimony, while tracing federal key court decisions and progeny. Civil
      and criminal cases are detailed to illustrate the application of these rules and
      case law to neuropsychological evidence, with suggestions for overcoming motions
      to exclude such evidence. Expert neuropsychologists have a role in forensic
      consultation on brain trauma cases, even as the interdisciplinary dialog and
      understanding among law, medicine, and psychology continues to expand.

PMID- 24115140
TI  - Metal cation controls myosin and actomyosin kinetics.
AB  - We have perturbed myosin nucleotide binding site with magnesium-, manganese-, or
      calcium-nucleotide complexes, using metal cation as a probe to examine the
      pathways of myosin ATPase in the presence of actin. We have used transient time
      resolved FRET, myosin intrinsic fluorescence, fluorescence of pyrene labeled
      actin, combined with the steady state myosin ATPase activity measurements of
      previously characterized D.discoideum myosin construct A639C:K498C. We found that
      actin activation of myosin ATPase does not depend on metal cation, regardless of
      the cation-specific kinetics of nucleotide binding and dissociation. The rate
      limiting step of myosin ATPase depends on the metal cation. The rate of the
      recovery stroke and the reverse recovery stroke is directly proportional to the
      ionic radius of the cation. The rate of nucleotide release from myosin and
      actomyosin, and ATP binding to actomyosin depends on the cation coordination
      number. 

PMID- 24115142
TI  - Oncologic safety of breast-conserving surgery compared to mastectomy in patients
      receiving neoadjuvant chemotherapy for locally advanced breast cancer.
AB  - BACKGROUND: Breast-conserving surgery (BCS) in patients with large tumors shrunk
      by neoadjuvant chemotherapy (NCT) remains controversial. We investigated
      oncologic outcomes of BCS in patients receiving NCT to treat locally advanced
      breast cancer (LABC). METHODS: We reviewed 1,994 patients who underwent surgery
      with/without NCT. Patients were categorized into three groups according to
      treatment methods: initial BCS, BCS after NCT (NCT-BCS), and mastectomy after NCT
      (NCT-MX). Their characteristics and outcomes were analyzed. RESULTS: The NCT-BCS
      group had earlier stage cancer, more hormone receptor-negative and triple
      negative breast cancers (TNBC) than the NCT-MX group. However, outcomes did not
      differ statistically between the two groups. BCS patients receiving NCT were
      younger, and had more advanced, hormone receptor-negative, HER2-positive, and
      TNBC breast cancers than BCS patients without NCT. Patients with pathological
      complete remission (pCR) in the NCT-BCS group had better survival outcomes than
      non-pCR patients and the initial BCS group. By multivariate analysis in patients
      receiving NCT, final stage and TNBC were associated with poor overall survival
      (stage III: P = 0.008; TNBC: P = 0.01), however surgery type was not (P = 0.20).
      CONCLUSIONS: BCS after NCT is a safe option for LABC that responded well to NCT.
      Shrinking tumors with NCT allows more opportunities to apply BCS without
      compromising outcomes.

PMID- 24115141
TI  - Antisomnogenic cytokines, quality of life, and chronic rhinosinusitis: a pilot
      study.
AB  - OBJECTIVES/HYPOTHESIS: Sleep disturbance, reduced quality of life (QOL), and
      other components of "sickness behavior" in patients with chronic rhinosinusitis
      (CRS) are poorly understood. These complex changes in central behavior are due to
      the effects of immune mediators acting in the brain. We hypothesized that immune
      mediators that have been associated with CRS are also associated with sickness
      behavior, somnifacient complaints, and CRS disease-specific QOL. STUDY DESIGN:
      Pilot study. METHODS: Twenty patients with CRS were prospectively enrolled and
      completed the Pittsburgh Sleep Quality Index (PSQI), disease-specific QOL, and
      olfactory instruments. Ethmoid mucosa was obtained and reverse transcription
      polymerase chain reaction was performed for the cytokines interleukin (IL)-4, 
      13, and transforming growth factor-beta (TGF-beta). Average change in crossover
      threshold was calculated, and differences in gene expression were correlated with
      sleep quality, CRS-specific QOL, and disease severity. RESULTS: Patients with CRS
      reported overall poor sleep quality and poor CRS-specific QOL with significant
      correlations between them. Increased expression of TGF-beta (r = -0.443; P =
      .050) and IL-4 (r = -0.548; P = .012) correlated with sleep dysfunction, whereas
      IL-13 expression was linearly associated with worse sleep quality (PSQI scores r
      = -0.417; P = .075). IL-4 and TGF-beta expression was not associated with CRS
      disease severity or QOL, whereas significantly higher levels of IL-13 expression
      correlated with worse CRS disease severity and QOL. CONCLUSIONS: Patients with
      CRS exhibited behavioral changes commonly referred to as sickness behavior, which
      include poor sleep quality and reduced QOL. The upregulation of IL-4 and TGF-beta
      may contribute to inflammatory brain-mediated effects on sleep quality, whereas
      IL-13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS
      disease severity. LEVEL OF EVIDENCE: 2b.

PMID- 24115143
TI  - Expanded organic building units for the construction of highly porous metal
      organic frameworks.
AB  - Two new organic building units that contain dicarboxylate sites for their self
      assembly with paddlewheel [Cu2(CO2)4] units have been successfully developed to
      construct two isoreticular porous metal-organic frameworks (MOFs), ZJU-35 and ZJU
      36, which have the same tbo topologies (Reticular Chemistry Structure Resource
      (RCSR) symbol) as HKUST-1. Because the organic linkers in ZJU-35 and ZJU-36 are
      systematically enlarged, the pores in these two new porous MOFs vary from 10.8 A
      in HKUST-1 to 14.4 A in ZJU-35 and 16.5 A in ZJU-36, thus leading to their higher
      porosities with Brunauer-Emmett-Teller (BET) surface areas of 2899 and 4014 m(2)
      g(-1) for ZJU-35 and ZJU-36, respectively. High-pressure gas-sorption isotherms
      indicate that both ZJU-35 and ZJU-36 can take up large amounts of CH4 and CO2,
      and are among the few porous MOFs with the highest volumetric storage of CH4
      under 60 bar and CO2 under 30 bar at room temperature. Their potential for high
      pressure swing adsorption (PSA) hydrogen purification was also preliminarily
      examined and compared with several reported MOFs, thus indicating the potential
      of ZJU-35 and ZJU-36 for this important application. Studies show that most of
      the highly porous MOFs that can volumetrically take up the greatest amount of CH4
      under 60 bar and CO2 under 30 bar at room temperature are those self-assembled
      from organic tetra- and hexacarboxylates that contain m-benzenedicarboxylate
      units with the [Cu2(CO2)4] units, because this series of MOFs can have balanced
      porosities, suitable pores, and framework densities to optimize their volumetric
      gas storage. The realization of the two new organic building units for their
      construction of highly porous MOFs through their self-assembly with [Cu2(CO2)4]
      units has provided great promise for the exploration of a large number of new
      tetra- and hexacarboxylate organic linkers based on these new organic building
      units in which different aromatic backbones can be readily incorporated into the
      frameworks to tune their porosities, pore structures, and framework densities,
      thus targeting some even better performing MOFs for very high gas storage and
      efficient gas separation under high pressure and at room temperature in the near
      future.

PMID- 24115144
TI  - Quantitative analysis of amygdalin and prunasin in Prunus serotina Ehrh. using
      (1) H-NMR spectroscopy.
AB  - INTRODUCTION: Prunus serotina is native to North America but has been invasively
      introduced in Europe since the seventeenth century. This plant contains
      cyanogenic glycosides that are believed to be related to its success as an
      invasive plant. For these compounds, chromatographic- or spectrometric-based
      (targeting on HCN hydrolysis) methods of analysis have been employed so far.
      However, the conventional methods require tedious preparation steps and a long
      measuring time. OBJECTIVE: To develop a fast and simple method to quantify the
      cyanogenic glycosides, amygdalin and prunasin in dried Prunus serotina leaves
      without any pre-purification steps using (1) H-NMR spectroscopy. METHODS:
      Extracts of Prunus serotina leaves using CH3 OH-d4 and KH2 PO4 buffer in D2 O
      (1:1) were quantitatively analysed for amygdalin and prunasin using (1) H-NMR
      spectroscopy. Different internal standards were evaluated for accuracy and
      stability. The purity of quantitated (1) H-NMR signals was evaluated using
      several two-dimensional NMR experiments. RESULTS: Trimethylsilylpropionic acid
      sodium salt-d4 proved most suitable as the internal standard for quantitative (1)
      H-NMR analysis. Two-dimensional J-resolved NMR was shown to be a useful tool to
      confirm the structures and to check for possible signal overlapping with the
      target signals for the quantitation. Twenty-two samples of P. serotina were
      subsequently quantitatively analysed for the cyanogenic glycosides prunasin and
      amygdalin. CONCLUSION: The NMR method offers a fast, high-throughput analysis of
      cyanogenic glycosides in dried leaves permitting simultaneous quantification and
      identification of prunasin and amygdalin in Prunus serotina.

PMID- 24115145
TI  - No evidence that associations of incident, sporadic colorectal adenoma with its
      major modifiable risk factors differ by chromosome 8q24 region rs6983267
      genotype.
AB  - A single nucleotide polymorphism (SNP), rs6983267, in the chromosome 8q24 region,
      has been associated with higher risk for colorectal neoplasms, but its relation
      to carcinogenic mechanisms is unclear. To investigate whether associations of
      colorectal adenoma with its major modifiable risk factors differ according to
      rs6983267 genotype, we performed a pooled analysis of the White participants (n =
      401 cases, 518 controls) from three colonoscopy-based, case-control studies of
      incident, sporadic colorectal adenoma conducted between 1991 and 2002. There was
      a statistically significant direct association of rs6983267 with colorectal
      adenoma that was consistent with those in previous reports. We found no clear
      indications that rs6983267 impacts the association of colorectal adenomas with
      the following risk factors: physical activity, body mass index (BMI),
      nonsteroidal anti-inflammatory drug (NSAID) use, tobacco or alcohol use, hormone
      replacement therapy among women, blood 25-OH-vitamin D3 levels, oxidative
      balance, or total energy, calcium, red meat, vegetable and fruit, and folate
      intakes. These findings, together with previously reported null results on 8q24
      environment interactions for colorectal cancer, suggest that associations of
      colorectal adenoma with its major modifiable risk factors may not differ
      according to chromosome 8q24 region rs6983267 genotype.

PMID- 24115146
TI  - Implications of intratumour heterogeneity for treatment stratification.
AB  - Despite advances in the diagnosis and treatment of cancer, the majority of
      advanced metastatic solid tumours remain incurable. Differential gene expression,
      somatic mutational status, tumour-specific genetic signatures and micro
      environmental selection pressures within individual tumours have implications for
      the success of predictive assays to guide therapeutic intervention. In this
      review we discuss the evidence for genetic and phenotypic heterogeneity and its
      potential implications for clinical decision making. We highlight areas of
      research that could be improved in order to better stratify patient treatment. We
      also discuss the predictive potential of patient-derived models of tumour
      response, including xenograft and cell line-based systems within the context of
      intratumour heterogeneity.

PMID- 24115147
TI  - Successful negative inotropic treatment of acute left ventricular outflow tract
      obstruction by elongated mitral valve leaflet.
AB  - Elongated anterior mitral valve leaflet (EAMVL) has not been reported to cause
      left ventricular outflow tract obstruction (LVOTO) in the absence of left
      ventricular hypertrophy. We report the case of an elderly male patient who
      presented with acute heart failure and severe mitral regurgitation in the setting
      of dehydration. Echocardiography revealed acute LVOTO secondary to EAMVL. The
      patient was ineligible for surgery and was treated with negative inotropic
      agents, which ensured resolution of heart failure and marked improvement in the
      degree of LVOTO. This case demonstrates that, under certain circumstances, EAMVL
      without associated left ventricular hypertrophy may produce hemodynamic
      compromise that can be successfully treated medically.

PMID- 24115148
TI  - SVR_CAF: an integrated score function for detecting native protein structures
      among decoys.
AB  - An accurate score function for detecting the most native-like models among a huge
      number of decoy sets is essential to the protein structure prediction. In this
      work, we developed a novel integrated score function (SVR_CAF) to discriminate
      native structures from decoys, as well as to rank near-native structures and
      select best decoys when native structures are absent. SVR_CAF is a machine
      learning score, which incorporates the contact energy based score (CE_score),
      amino acid network based score (AAN_score), and the fast Fourier transform based
      score (FFT_score). The score function was evaluated with four decoy sets for its
      discriminative ability and it shows higher overall performance than the state-of
      the-art score functions.

PMID- 24115149
TI  - Cerebral arterial and venous blood flow in adolescent multiple sclerosis patients
      and age-matched controls using phase contrast MRI.
AB  - PURPOSE: Altered cerebrovascular blood flow has been proposed as a mechanism for
      multiple sclerosis (MS). The primary objective of this study was to measure
      arterial and venous blood flow in adolescent MS patients and healthy controls
      (HC), in whom confounding factors such as age and lifestyle are less influential.
      MATERIALS AND METHODS: Phase-contrast magnetic resonance imaging (MRI) was used
      to measure flow in 26 MS patients and 26 controls aged 17.7 +/- 1.8 and 17.8 +/-
      2.1 years, respectively. Flow was measured in the left and right internal carotid
      arteries (ICA), vertebral arteries (VA), internal jugular veins (IJV), and
      epidural veins (EV). Eighteen MS patients returned for a second MRI examination
      after 6 months. In all participants, ultrasound criteria for chronic
      cerebrospinal venous insufficiency (CCSVI) were also evaluated. RESULTS: Flows
      (mL/min) in the MS group versus HC group were as follows: right ICA = 262 +/- 57
      vs. 263 +/- 32, left ICA = 260 +/- 67 vs. 270 +/- 36, right VA = 96 +/- 50 vs.
      103 +/- 30, left VA = 104 +/- 37 vs. 118 +/- 41, right IJV = 342 +/- 180 vs. 345
      +/- 195, left IJV = 190 +/- 131 vs. 250 +/- 148, right EV = 33 +/- 29 vs. 48 +/-
      43, and left EV = 36 +/- 35 vs. 44 +/- 28 (P > 0.17 for all comparisons). In MS
      participants, a nonsignificant trend to lower flow in the left IJV was observed,
      and the flow pulsatility index in the epidural veins was higher. Two MS
      participants met ultrasound criteria for CCSVI, but no significant difference in
      flow was detected. CONCLUSION: No population difference in flow rate was detected
      in adolescent MS participants relative to age-matched controls.

PMID- 24115150
TI  - Occupational exposure levels of static magnetic field during routine MRI
      examination in 3T MR system.
AB  - Occupational exposure to the high static magnetic fields (SMFs) during magnetic
      resonance imaging (MRI) examinations raises concerns of adverse health effects.
      In this study, personal exposure monitoring of the magnetic fields during routine
      examinations in two 3 T MRI systems was carried out. A three-axis Hall
      magnetometer was attached to a subject's chest during monitoring. Data
      acquisition started every time the subject entered the scanner room and ended
      when the subject exited the room. Four radiologic technologists from two
      different institutes participated in this study. The maximum exposed field ranged
      from 0 to 1250 mT and the average peak magnetic field (B) was 428 +/- 231 mT
      (mean +/- standard deviation (SD): number of samples (N) = 103). Then, the
      relationship between exposure levels and work duties was analyzed. The MRI
      examination of the head or neck showed the highest average peak B among four work
      categories. These results provide information of real exposure levels for 3 T MRI
      system operators and can also improve the current practical training advice for
      preventing extra occupational field exposure.

PMID- 24115151
TI  - Tailor-made hole-conducting coadsorbents for highly efficient organic dye
      sensitized solar cells.
AB  - The Y-shaped, low molecular mass, hole-conductor (HC), acidic coadsorbents 4-{3,7
      bis[4-(2-ethylhexyloxy)phenyl]-10H-phenothiazin-10-yl}benzoic acid (PTZ1) and 4
      {3,7-bis[4-(2-ethylhexyloxy)phenyl]-10H-phenothiazin-10-yl}biphenyl-4-carboxylic
      acid (PTZ2) were developed. Owing to their tuned and negative-shifted HOMO levels
      (vs. NHE), they were used as HC coadsorbents in dye-sensitized solar cells
      (DSSCs) to improve cell performance through desired cascade-type hole-transfer
      processes. Their detailed functions as HC coadsorbents in DSSCs were investigated
      to obtain evidence for the desired cascade-type hole-transfer processes. They
      have multiple functions, such as preventing pi-pi stacking of dye molecules,
      harvesting light of shorter wavelengths, and faster dye regeneration. By using
      PTZ2 as the tailor-made HC coadsorbent on the TiO2 surface with the organic dye
      NKX2677, an extremely high conversion efficiency of 8.95 % was achieved under 100
      mW cm(-2) AM 1.5G simulated light (short-circuit current JSC =16.56 mA cm(-2) ,
      open-circuit voltage VOC =740 mV, and fill factor of 73 %). Moreover, JSC was
      increased by 13 %, VOC by 27 % and power-conversion efficiency by 49 % in
      comparison to an NKX2677-based DSSC without an HC coadsorbent. This is due to the
      HC coadsorbent having a HOMO energy level well matched to that of the NKX-2677
      dye to induce the desired cascade-type hole-transfer processes, which are
      associated with a slower charge recombination, fast dye regeneration, effective
      screening of liquid electrolytes, and an induced negative shift of the quasi
      Fermi level of the electrode. Thus, this new class of Y-shaped, low molecular
      weight, organic, HC coadsorbents based on phenothiazine carboxylic acid
      derivatives hold promise for highly efficient organic DSSCs.

PMID- 24115152
TI  - Ultra-high-performance liquid chromatography-tandem mass spectrometry for
      pharmacokinetics of bakuchiol in rats.
AB  - Psoralea Corylifolia L. is a traditional Chinese medicine with many beneficial
      effects in medical therapies. Bakuchiol was the main active ingredient of
      Psoralea Corylifolia L., used for the treatment of various diseases and also as a
      natural food additive. A specific and reliable ultra-high performance liquid
      chromatography-tandem mass spectrometry has been developed and fully validated
      for the quantification of bakuchiol in rat plasma. Chromatographic separation of
      bakuchiol and an internal standard, daidzein, was achieved on a Hypersil Gold C18
      column with gradient elution that consisted of methanol and water at a flow rate
      of 0.2 mL/min. The compounds were detected at negative ionization mode using mass
      transition m/z 255.2 -> 172.0 and 252.9 -> 132.0 for bakuchiol and daidzein,
      respectively. Good linearity was obtained over the range of 2-1000 ng/mL and the
      lower limit of quantification was 2 ng/mL. The intra- and inter-day accuracies
      ranged from 91.1 to 105.7% and precisions (relative standard deviations) were
      within 9.3%. Bakuchiol was found to be stable under three freeze-thaw cycles,
      short-term temperature, post-preparative and long-term temperature conditions.
      The method was applied to a pharmacokinetic study of bakuchiol intravenously
      administered to rats at a dose of 5 mg/kg.

PMID- 24115153
TI  - Gradient elution moving boundary electrophoresis with channel current detection
      in relatively long capillaries.
AB  - A variant of gradient elution moving boundary electrophoresis with channel
      current detection is described, which uses relatively long channels (1.5 cm) for
      separation and detection. The signal for each analyte is determined to have the
      shape of a parabola ending with a break in slope. The capabilities of the new
      method are demonstrated for separation and quantitation of ATP and ADP, a
      measurement relevant for high-throughput screening assays. The results indicate
      that the new method is capable of reproducibly measuring the ratio of ADP
      concentration to ATP plus ADP concentration with an analysis time of less than 2
      min and with a 1 SD uncertainty of 0.018 (over a range of 0-1). 

PMID- 24115154
TI  - Proliferative verrucous leukoplakia: recognition and differentiation from
      conventional leukoplakia and mimics.
AB  - The majority of conventional leukoplakia remains constant and only a subset
      progress to high-grade dysplasia or invasive carcinoma. A less recognized form
      known as proliferative verrucous leukoplakia (PVL) represents a unique
      progressive and elusive variant. Identifying patients with this form can only be
      achieved through the keen clinical observation of the temporal gross and
      histologic progression in individual patients with squamous cell carcinoma. The
      difficulty in the early diagnosis of PVL stems from the overlapping clinical and
      pathologic features with conventional multifocal leukoplakia with dysplasia. We
      present the current view on the clinicopathologic and biological characteristics
      of PVL and discuss their diagnosis, differential diagnosis, and management.

PMID- 24115155
TI  - Introduction to this issue: traumatic brain injury.

PMID- 24115156
TI  - Selective CGRP and adrenomedullin peptide binding by tethered RAMP-calcitonin
      receptor-like receptor extracellular domain fusion proteins.
AB  - Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are related
      peptides that are potent vasodilators. The CGRP and AM receptors are heteromeric
      protein complexes comprised of a shared calcitonin receptor-like receptor (CLR)
      subunit and a variable receptor activity modifying protein (RAMP) subunit. RAMP1
      enables CGRP binding whereas RAMP2 confers AM specificity. How RAMPs determine
      peptide selectivity is unclear and the receptor stoichiometries are a topic of
      debate with evidence for 1:1, 2:2, and 2:1 CLR:RAMP stoichiometries. Here, we
      describe bacterial production of recombinant tethered RAMP-CLR extracellular
      domain (ECD) fusion proteins and biochemical characterization of their peptide
      binding properties. Tethering the two ECDs ensures complex stability and enforces
      defined stoichiometry. The RAMP1-CLR ECD fusion purified as a monomer, whereas
      the RAMP2-CLR ECD fusion purified as a dimer. Both proteins selectively bound
      their respective peptides with affinities in the low micromolar range. Truncated
      CGRP(27-37) and AM(37-52) fragments were identified as the minimal ECD complex
      binding regions. The CGRP C-terminal amide group contributed to, but was not
      required for, ECD binding, whereas the AM C-terminal amide group was essential
      for ECD binding. Alanine-scan experiments identified CGRP residues T30, V32, and
      F37 and AM residues P43, K46, I47, and Y52 as critical for ECD binding. Our
      results identify CGRP and AM determinants for receptor ECD complex binding and
      suggest that the CGRP receptor functions as a 1:1 heterodimer. In contrast, the
      AM receptor may function as a 2:2 dimer of heterodimers, although our results
      cannot rule out 2:1 or 1:1 stoichiometries. 

PMID- 24115157
TI  - Osterix and NO66 histone demethylase control the chromatin of Osterix target
      genes during osteoblast differentiation.
AB  - Commitment of Runx2-expressing precursor osteoblasts to functional osteoblasts
      and then to osteocytes is triggered by Osterix (Osx), which activates its target
      genes in those cells during bone formation. It is not yet known whether Osx has a
      role in remodeling the chromatin architecture of its target genes during the
      transition from preosteoblast to osteoblast. In testing the hypothesis that Osx
      is indispensable for active chromatin architecture, we first showed that in Osx
      null calvarial cells occupancy of the transcriptional activators, including
      lysine 4 methyl transferase (Wdr5), c-Myc, and H2A.Z, at the Osx target gene Bsp
      was very markedly decreased. The levels of methylation of lysines 4 and 36 and
      acetylation of histone H3, markers for active chromatin, were also reduced at the
      Bsp gene in these cells. In contrast, occupancy of the transcriptional repressors
      HP1 and the nucleolar protein 66 (NO66), a histone demethylase previously
      identified as an Osx-interacting protein, was increased at the Bsp gene in Osx
      null calvarial cells. Furthermore, the Bsp promoter was hypermethylated in
      embryonic stem (ES) cells and in embryonic day 9.5 (E9.5) embryos but was
      markedly hypomethylated in the calvaria of E18.5 embryos, coinciding with robust
      Bsp expression. In contrast, CpG methylation in the Bsp promoter remained high in
      Osx-null calvaria compared to Osx-wild-type calvaria. Our data also revealed that
      NO66 interacted with DNA Methyltransferase 1A (DNMT1A), histone deacetylase 1A
      (HDAC1A), and HP1, which are known to control histone and DNA methylation. In
      addition, HP1 stimulated the demethylase activity of NO66 for its substrates
      "trimethylation of histone H3 at lysine 4" (H3K4me3) and "trimethylation of
      histone H3 at lysine 36" (H3K36me3). Our findings strongly suggest that in the
      absence of Osx, the chromatin of Osx target genes is transcriptionally inactive.
      We propose that Osx is a molecular switch for the formation of an active
      chromatin state during osteoblast differentiation, whereas NO66 helps gene
      repression through histone demethylation and/or formation of a repressor complex,
      resulting in multilayered control of the chromatin architecture of specific
      osteoblast genes.

PMID- 24115158
TI  - G-protein-coupled receptor 30/adenylyl cyclase/protein kinase A pathway is
      involved in estradiol 17beta-D-glucuronide-induced cholestasis.
AB  - Estradiol-17beta-D-glucuronide (E17G) activates different signaling pathways
      (e.g., Ca(2+) -dependent protein kinase C, phosphoinositide 3-kinase/protein
      kinase B, mitogen-activated protein kinases [MAPKs] p38 and extracellular signal
      related kinase 1/2, and estrogen receptor alpha) that lead to acute cholestasis
      in rat liver with retrieval of the canalicular transporters, bile salt export
      pump (Abcb11) and multidrug resistance-associated protein 2 (Abcc2). E17G shares
      with nonconjugated estradiol the capacity to activate these pathways. G-protein
      coupled receptor 30 (GPR30) is a receptor implicated in nongenomic effects of
      estradiol, and the aim of this study was to analyze the potential role of this
      receptor and its downstream effectors in E17G-induced cholestasis. In vitro,
      GPR30 inhibition by G15 or its knockdown with small interfering RNA strongly
      prevented E17G-induced impairment of canalicular transporter function and
      localization. E17G increased cyclic adenosine monophosphate (cAMP) levels, and
      this increase was blocked by G15, linking GPR30 to adenylyl cyclase (AC).
      Moreover, AC inhibition totally prevented E17G insult. E17G also increased
      protein kinase A (PKA) activity, which was blocked by G15 and AC inhibitors,
      connecting the links of the pathway, GPR30-AC-PKA. PKA inhibition prevented E17G
      induced cholestasis, whereas exchange protein activated directly by cyclic
      nucleotide/MAPK kinase, another cAMP downstream effector, was not implicated in
      cAMP cholestatic action. In the perfused rat liver model, inhibition of the GPR30
      AC-PKA pathway totally prevented E17G-induced alteration in Abcb11 and Abcc2
      function and localization. CONCLUSION: Activation of GPR30-AC-PKA is a key factor
      in the alteration of canalicular transporter function and localization induced by
      E17G. Interaction of E17G with GPR30 may be the first event in the cascade of
      signaling activation.

PMID- 24115160
TI  - Robotic microlaryngeal surgery: feasibility using a newly designed retractor and
      instrumentation.
AB  - OBJECTIVES/HYPOTHESIS: Robotic surgery is increasingly used for a variety of head
      and neck surgical procedures but has yet to be adapted for routine robotic
      microlaryngeal surgery (RMLS). Current retractor technology is limited by the
      following: poor tongue retraction, poor oral commissure retraction, poor larynx
      visualization, and laryngeal blades that do not take advantage of the robot's
      ability to operate without line-of-site exposure. Additionally, adequate
      instrumentation for RMLS is lacking. STUDY DESIGN: Feasibility study. METHODS: We
      performed a feasibility study of RMLS using a newly designed robotic retractor in
      a cadaver model with the goal of routinely exposing the glottis. Microlaryngeal
      instrumentation was also adapted for the da Vinci Surgical Robot effector arms.
      RESULTS: RMLS surgery was successfully performed including microflap elevation,
      anterior commissure surgery, false cordectomy, true cordotomy/cordectomy, and
      arytenoidectomy. Photographic and video documentation was obtained demonstrating
      feasibility. CONCLUSIONS: We present a newly designed laryngeal robotic retractor
      and novel microlaryngeal instrumentation in a cadaveric model. This allows for
      glottic and anterior commissure exposure, effector arm access to the glottis, and
      performance of delicate endolaryngeal procedures with the robot. The overall
      efficacy of our retractor will need to be examined in an in vivo human model.
      LEVEL OF EVIDENCE: NA.

PMID- 24115159
TI  - The role of anterior midcingulate cortex in cognitive motor control: evidence
      from functional connectivity analyses.
AB  - The rostral cingulate cortex has been associated with a multitude of cognitive
      control functions. Recent neuroimaging data suggest that the anterior
      midcingulate cortex (aMCC) has a key role for cognitive aspects of movement
      generation, i.e., intentional motor control. We here tested the functional
      connectivity of this area using two complementary approaches: (1) resting-state
      connectivity of the aMCC based on fMRI scans obtained in 100 subjects, and (2)
      functional connectivity in the context of explicit task conditions using meta
      analytic connectivity modeling (MACM) over 656 imaging experiment. Both
      approaches revealed a convergent functional network architecture of the aMCC with
      prefrontal, premotor and parietal cortices as well as anterior insula, area
      44/45, cerebellum and dorsal striatum. To specifically test the role of the
      aMCC's task-based functional connectivity in cognitive motor control, separate
      MACM analyses were conducted over "cognitive" and "action" related experimental
      paradigms. Both analyses confirmed the same task-based connectivity pattern of
      the aMCC. While the "cognition" domain showed higher convergence of activity in
      supramodal association areas in prefrontal cortex and anterior insula, "action"
      related experiments yielded higher convergence in somatosensory and premotor
      areas. Secondly, to probe the functional specificity of the aMCC's convergent
      functional connectivity, it was compared with a neural network of intentional
      movement initiation. This exemplary comparison confirmed the involvement of the
      state independent FC network of the aMCC in the intentional generation of
      movements. In summary, the different experiments of the present study suggest
      that the aMCC constitute a key region in the network realizing intentional motor
      control.

PMID- 24115161
TI  - Mathematical modelling of digit specification by a sonic hedgehog gradient.
AB  - BACKGROUND: The three chick wing digits represent a classical example of a
      pattern specified by a morphogen gradient. Here we have investigated whether a
      mathematical model of a Shh gradient can describe the specification of the
      identities of the three chick wing digits and if it can be applied to limbs with
      more digits. RESULTS: We have produced a mathematical model for specification of
      chick wing digit identities by a Shh gradient that can be extended to the four
      digits of the chick leg with Shh-producing cells forming a digit. This model
      cannot be extended to specify the five digits of the mouse limb. CONCLUSIONS: Our
      data suggest that the parameters of a classical-type morphogen gradient are
      sufficient to specify the identities of three different digits. However, to
      specify more digit identities, this core mechanism has to be coupled to
      alternative processes, one being that in the chick leg and mouse limb, Shh
      producing cells give rise to digits; another that in the mouse limb, the cellular
      response to the Shh gradient adapts over time so that digit specification does
      not depend simply on Shh concentration.

PMID- 24115162
TI  - Restoration of scarred vocal folds using 5 amino acid-deleted type hepatocyte
      growth factor.
AB  - OBJECTIVES/HYPOTHESIS: Our previous studies demonstrated a regenerative effect of
      recombinant human hepatocyte growth factor (HGF) on vocal fold scarring using
      full-length HGF. However, clinical application has not yet been achieved because
      of the lack of a good manufacturing practice (GMP) for full-length HGF. Another
      natural form of human HGF, 5 amino acid-deleted type HGF (dHGF), has been newly
      produced under a GMP procedure. In the current study, we investigated the effect
      of dHGF in comparison with full-length HGF for the treatment of vocal fold scars
      using a canine model. STUDY DESIGN: Prospective animal experiment. METHODS: The
      vocal folds of nine beagles were unilaterally injured. Four weeks after injury,
      the vocal folds were treated with an intracordal injection of full-length HGF
      (full HGF group), dHGF (dHGF group), or phosphate-buffered saline (sham group).
      Vibratory and histological examinations were performed for each group 6 months
      after injury. RESULTS: Vibratory examinations demonstrated significantly lower
      phonation threshold pressure and a higher ratio of normalized mucosal wave
      amplitude in both the full HGF and dHGF groups as compared to the sham group.
      Histological examination showed restoration of hyaluronic acid in both the full
      HGF and dHGF groups as compared to the sham group. No significant differences
      were observed for each parameter between the full HGF group and the dHGF group.
      CONCLUSIONS: dHGF showed the same potential for regenerative effects on vocal
      fold scars as full-length HGF. dHGF should be applicable for human clinical
      trials in patients with vocal fold scars.

PMID- 24115163
TI  - Preparative isolation of six anti-tumour biflavonoids from Selaginella
      doederleinii Hieron by high-speed counter-current chromatography.
AB  - INTRODUCTION: Biflavonoids are the primary constituents of Selaginella
      doederleinii Hieron, to which different bioactivities have been attributed,
      including anti-cancer, anti-inflammatory, anti-oxidant, anti-fungal and anti
      virus activity. However, effective methods for separation of these compounds are
      not currently available. OBJECTIVE: To develop a high performance and bioassay
      guided method for preparative isolation of biflavonoids from S. doederleini via
      high-speed counter-current chromatography (HSCCC). METHODS: The anti
      proliferation effects of four fractions (70% ethanol, petroleum ether,
      dichloromethane and acetic ether extracts) of S. doederleinii on five human
      cancer cells were monitored. The dichloromethane and acetic ether extracts showed
      good cytotoxicities to the studied cancer cell lines, guiding the subsequent
      separation. Two solvent systems composed of n-hexane:ethyl acetate:methanol:water
      (1:2:1.5:1.5, v/v) and n-hexane:ethyl acetate:methanol:water (3:2:3:2, v/v) were
      developed for separation of the active fractions, respectively. Identification of
      the biflavonoids was performed by EI-MS(n) , (1) H- and (13) C-NMR.' RESULTS:
      Under the optimised conditions, 12.6 mg amentoflavone (91.4%), 6.6 mg
      robustaflavone (90.4%), 7.5 mg 2'', 3''-dihydro-3', 3'''-biapigenin (98.2%) and
      7.3 mg 3', 3'''-binaringenin (90.3%) from acetic ether extract (500 mg) and 6.3
      mg heveaflavone (93.5%) and 5.3 mg 7, 4', 7'', 4'''-tetra-O-methyl-amentoflavone
      (94.5%) from dichloromethane extract (200 mg) were obtained, respectively. The
      anti-proliferation effects of the six biflavonoids on the five human cancer cells
      were further verified. CONCLUSION: The study provides methodological references
      for simultaneously preparative isolation of several bioactive biflavones from the
      herbal family of Selaginella. It is the first report discovering 2'', 3''-dihydro
      3', 3'''-biapigenin and 3', 3'''-binaringenin from this herb and describing their
      cytotoxicities to human cancer cell lines.

PMID- 24115164
TI  - The remission from depression questionnaire as an outcome measure in the
      treatment of depression.
AB  - BACKGROUND: The Remission from Depression Questionnaire (RDQ) assesses multiple
      domains considered by depressed patients to be relevant to the construct of
      remission. The present study is the first to examine the validity of the RDQ as
      an outcome measure. METHODS: One hundred fifty-three depressed patients who
      presented for treatment, or who were in ongoing treatment and had their
      medication changed, were evaluated at baseline and at 4-month follow-up. In
      addition to the RDQ, the patients completed the Quick Inventory of Depressive
      Symptomatology (QIDS), and they were rated on 17-item Hamilton Rating Scale for
      Depression (HAMD). RESULTS: The patients showed significant levels of improvement
      from baseline to 4 months on each scale. The effect size of the RDQ total score
      was similar to the effect sizes of the HAMD and QIDS. Both the RDQ and QIDS were
      significantly associated with patients' self-reported remission status. However,
      the RDQ remained significantly associated with remission status after controlling
      for QIDS scores, whereas the QIDS was not associated with remission status after
      controlling for RDQ scores. DISCUSSION: The RDQ is as sensitive to change as
      purely symptom-based scales such as the QIDS and HAMD. Moreover, the RDQ accounts
      for variation in patients' self-perceived remission status after controlling for
      QIDS scores, but the reverse was not true. The RDQ allows clinicians and
      researchers to gain a broader perspective of depressed patients' status than
      purely symptom measures, and is more consistent with a biopsychosocial approach
      toward the treatment of depression.

PMID- 24115165
TI  - A new approach for the laboratory culture of the fathead minnow, Pimephales
      promelas.
AB  - Fathead minnows are routinely cultured for use in aquatic toxicology studies. A
      new mass culture system described in the present study consisted of 6 stainless
      steel tanks, each containing 68 fish and 20 spawning substrates. Spawning results
      are compared with a previous system of 22 individual glass aquaria, which
      contained 16 fish and 4 spawning substrates per tank. During a 19-mo period, the
      new system produced an average of 4105 eggs/d, compared with an average of 2465
      eggs/d with the previous system. Labor and maintenance were reduced with the new
      system. The stainless steel tanks eliminated aquaria glass breakage, and daily
      water use was reduced by 45%. Analysis of reference toxicant data from fish
      cultured using both systems indicated no change in the sensitivity of the test
      animals. Analyses of 2009 egg production data determined that a 6:1 to 7:1 female
      to male ratio had a significantly positive impact on egg production levels and
      that 6-mo-old breeding stock should be introduced to the spawning tanks in mid
      spring for optimal egg production during the rest of the year. Implementing a
      stainless steel mass culture system significantly increased efficiency of egg
      production; reduced turnaround delay of mature animal availability for toxicity
      and molecular testing; and reduced labor time, costs, and inherent safety
      hazards, compared with glass aquaria systems.

PMID- 24115166
TI  - Therapeutic potentials of ecto-nucleoside triphosphate diphosphohydrolase, ecto
      nucleotide pyrophosphatase/phosphodiesterase, ecto-5'-nucleotidase, and alkaline
      phosphatase inhibitors.
AB  - The modulatory role of extracellular nucleotides and adenosine in relevance to
      purinergic cell signaling mechanisms has long been known and is an object of much
      research worldwide. These extracellular nucleotides are released by a variety of
      cell types either innately or as a response to patho-physiological stress or
      injury. A variety of surface-located ecto-nucleotidases (of four major types;
      nucleoside triphosphate diphosphohydrolases or NTPDases, nucleotide
      pyrophosphatase/phosphodiesterases or NPPs, alkaline phosphatases APs or ALPs,
      and ecto-5'-nucleotidase or e5NT) are responsible for meticulously controlling
      the availability of these important signaling molecules (at their respective
      receptors) in extracellular environment and are therefore crucial for maintaining
      the integrity of normal cell functioning. Overexpression of many of these
      ubiquitous ecto-enzymes has been implicated in a variety of disorders including
      cell adhesion, activation, proliferation, apoptosis, and degenerative
      neurological and immunological responses. Selective inhibition of these ecto
      enzymes is an area that is currently being explored with great interest and hopes
      remain high that development of selective ecto-nucleotidase inhibitors will prove
      to have many beneficial therapeutic implications. The aim of this review is to
      emphasize and focus on recent developments made in the field of inhibitors of
      ecto-nucleotidases and to highlight their structure activity relationships
      wherever possible. Most recent and significant advances in field of NTPDase, NPP,
      AP, and e5NT inhibitors is being discussed in detail in anticipation of providing
      prolific leads and relevant background for research groups interested in
      synthesis of selective ecto-nucleotidase inhibitors. 

PMID- 24115168
TI  - orthAgogue: an agile tool for the rapid prediction of orthology relations.
AB  - MOTIVATION: The comparison of genes and gene products across species depends on
      high-quality tools to determine the relationships between gene or protein
      sequences from various species. Although some excellent applications are
      available and widely used, their performance leaves room for improvement.
      RESULTS: We developed orthAgogue: a multithreaded C application for high-speed
      estimation of homology relations in massive datasets, operated via a flexible and
      easy command-line interface. AVAILABILITY: The orthAgogue software is distributed
      under the GNU license. The source code and binaries compiled for Linux are
      available at https://code.google.com/p/orthagogue/.

PMID- 24115167
TI  - Development of intestinal organoids as tissue surrogates: cell composition and
      the epigenetic control of differentiation.
AB  - Intestinal organoids are multicellular crypt-like structures that can be derived
      from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs) or induced
      pluripotent stem cells (IPSCs). Here we show that intestinal organoids generated
      from mouse ESCs were enriched in ISCs and early progenitors. Treatment of these
      organoids with a gamma-secretase inhibitor increased Math1 and decreased Hes1
      expression, indicating Notch signaling regulates ISC differentiation in these
      organoids. Lgr5 and Tert positive ISCs constituted approximately 10% and 20% of
      the organoids. As found in native tissue, Lgr5 and Tert expressing cells resolved
      into two discreet populations, which were stable over time. Intestinal organoids
      derived from cancer-prone Apc(Min/+) mice showed similar numbers of ISCs, but had
      reduced Math1 expression, indicating a suppressed secretory cell differentiation
      potential (as found in intestinal tissue). Apc(Min/+) organoids were used to
      screen epigenetically active compounds for those that increased Math1 expression
      and organoid differentiation (including HDAC inhibitors, Sirtuin (SIRT)
      modulators and methyltransferase inhibitors). Broad-spectrum HDAC inhibitors
      increased both Math1 and Muc2 expression, indicating an ability to promote the
      suppressed secretory cell differentiation pathway. Other epigenetic compounds had
      a diverse impact on cell differentiation, with a strong negative correlation
      between those that activated the secretory marker Muc2 and those that activated
      the absorptive cell marker Fabp2. These data show that ESC-derived intestinal
      organoids can be derived in large numbers, contain distinct ISC types and can be
      used to screen for agents that promote cell differentiation through different
      lineage pathways.

PMID- 24115169
TI  - A penalized Bayesian approach to predicting sparse protein-DNA binding
      landscapes.
AB  - MOTIVATION: Cellular processes are controlled, directly or indirectly, by the
      binding of hundreds of different DNA binding factors (DBFs) to the genome. One
      key to deeper understanding of the cell is discovering where, when and how
      strongly these DBFs bind to the DNA sequence. Direct measurement of DBF binding
      sites (BSs; e.g. through ChIP-Chip or ChIP-Seq experiments) is expensive, noisy
      and not available for every DBF in every cell type. Naive and most existing
      computational approaches to detecting which DBFs bind in a set of genomic regions
      of interest often perform poorly, due to the high false discovery rates and
      restrictive requirements for prior knowledge. RESULTS: We develop SparScape, a
      penalized Bayesian method for identifying DBFs active in the considered regions
      and predicting a joint probabilistic binding landscape. Using a sparsity-inducing
      penalization, SparScape is able to select a small subset of DBFs with enriched
      BSs in a set of DNA sequences from a much larger candidate set. This
      substantially reduces the false positives in prediction of BSs. Analysis of ChIP
      Seq data in mouse embryonic stem cells and simulated data show that SparScape
      dramatically outperforms the naive motif scanning method and the comparable
      computational approaches in terms of DBF identification and BS prediction.
      AVAILABILITY AND IMPLEMENTATION: SparScape is implemented in C++ with OpenMP
      (optional at compilation) and is freely available at
      'www.stat.ucla.edu/~zhou/Software.html' for academic use.

PMID- 24115170
TI  - Conformational diversity in contryphans from Conus venom: cis-trans isomerisation
      and aromatic/proline interactions in the 23-membered ring of a 7-residue peptide
      disulfide loop.
AB  - Conformational diversity or "shapeshifting" in cyclic peptide natural products
      can, in principle, confer a single molecular entity with the property of binding
      to multiple receptors. Conformational equilibria have been probed in the
      contryphans, which are peptides derived from Conus venom possessing a 23-membered
      cyclic disulfide moiety. The natural sequences derived from Conus inscriptus,
      GCV(D)LYPWC* (In936) and Conus loroisii, GCP(D)WDPWC* (Lo959) differ in the
      number of proline residues within the macrocyclic ring. Structural
      characterisation of distinct conformational states arising from cis-trans
      equilibria about Xxx-Pro bonds is reported. Isomerisation about the C2-P3 bond is
      observed in the case of Lo959 and about the Y5-P6 bond in In936. Evidence is
      presented for as many as four distinct species in the case of the synthetic
      analogue V3P In936. The Tyr-Pro-Trp segment in In936 is characterised by distinct
      sidechain orientations as a consequence of aromatic/proline interactions as
      evidenced by specific sidechain-sidechain nuclear Overhauser effects and ring
      current shifted proton chemical shifts. Molecular dynamics simulations suggest
      that Tyr5 and Trp7 sidechain conformations are correlated and depend on the
      geometry of the Xxx-Pro bond. Thermodynamic parameters are derived for the cis<
      >trans equilibrium for In936. Studies on synthetic analogues provide insights
      into the role of sequence effects in modulating isomerisation about Xxx-Pro
      bonds.

PMID- 24115171
TI  - Ratiometric fluorescent probes for hydrogen peroxide from a focused library.

PMID- 24115172
TI  - Proteomic and redox-proteomic study on the role of glutathione reductase in human
      lung cancer cells.
AB  - Glutathione reductase (GR), a cytosolic protein, plays a vital role in
      maintaining a correct redox status in cells. However, comprehensive
      investigations of GR-modulated cellular responses, including protein level
      alteration and redox regulation, have yet to be performed. In this study, we
      cultured a human lung adenocarcinoma line transfected with empty pLKO.1 vector as
      a control, CL1-0shControl, and its GR-knockdown derivative, CL1-0shDeltaGR, to
      evaluate differential protein level alteration and redox regulation of these two
      cell lines. We identified 34 spots that exhibited marked changes in intensities,
      and 13 proteins showing significant changes in thiol reactivity, in response to
      GR depletion. Several proteins involved in redox regulation, calcium signaling,
      cytoskeleton regulation, and protein folding showed significant changes in
      expression, whereas proteins involved in redox regulation, protein folding, and
      glycolysis displayed changes in thiol reactivity. Interestingly, GR knockdown
      induces peroxiredoxin-1 overexpression in the air-exposed tissue and high oxygen
      consuming tissue such as cornea and liver, but not in the low oxygen consuming
      tissues such as breast and uterine. In summary, we used a comprehensive lung
      adenocarcinoma based proteomic approach for identifying GR-modulated protein
      expression alteration and redox modification. Based on our research, this is the
      first comprehensive proteomic and redox-proteomic analysis used to investigate
      the role of GR in a mammalian cell model. 

PMID- 24115173
TI  - Concerning the structure of apoE.
AB  - Apolipoprotein E (apoE), first described in 1973, is a truly fascinating protein.
      While studies initially focused on its role in cholesterol and lipid metabolism,
      one apoE isoform (apoE4) is a major risk factor for development of late onset
      Alzheimer's disease. Yet the difference between apoE3, the common form, and apoE4
      is a single amino acid of the 299 in this 34 kDa protein. Structure determination
      of the two domain full length apoE3 protein was only accomplished in 2011 and
      supports the notion that mutations in the N-terminal domain can be propagated
      through the structure to the C-terminal domain. Understanding the structural
      differences between apoE3 and apoE4 is critical for finding ways to modulate the
      deleterious effect of apoE4. 

PMID- 24115174
TI  - Body signals during social play in free-ranging rhesus macaques (Macaca mulatta):
      A systematic analysis.
AB  - Social play involves one of the most sophisticated types of communication, that
      is, the use of play signals. Most primate research on play signals has focused on
      the use of the play face. However, some species appear to exhibit a variety of
      play signals. For example, rhesus monkeys (Macaca mulatta) have been reported to
      use body movements or postures that might have signal value during social play,
      in addition to the play face. However, it is not clear whether these body signals
      actually meet several criteria necessary to label them as "play signals." Here we
      examine the forms and possible functions of seven candidate signals that we
      observed exclusively during social play contexts among free-ranging rhesus
      monkeys on Cayo Santiago. We aim to (1) distinguish them from actual play
      behavior (play involving contact or chasing) using loglinear analysis and (2)
      determine whether they predict playful behavior using modified PC-MC methods. Two
      candidate signals did not resemble any behaviors used in actual play. The other
      five signals contained elements that lasted longer or increased their
      conspicuousness over similar play behaviors, suggesting ritualized
      characteristics. Youngsters were likely to initiate contact or chasing play
      significantly sooner after candidate signals than in their absence. Thus, these
      candidate signals appear to meet critical criteria of signals that promote,
      moderate or facilitate play. As such, these findings open the door to questions
      about why multiple play signals have evolved.

PMID- 24115175
TI  - Automatic segmentation of invasive breast carcinomas from dynamic contrast
      enhanced MRI using time series analysis.
AB  - PURPOSE: To accurately segment invasive ductal carcinomas (IDCs) from dynamic
      contrast-enhanced MRI (DCE-MRI) using time series analysis based on linear
      dynamic system (LDS) modeling. MATERIALS AND METHODS: Quantitative segmentation
      methods based on black-box modeling and pharmacokinetic modeling are highly
      dependent on imaging pulse sequence, timing of bolus injection, arterial input
      function, imaging noise, and fitting algorithms. We modeled the underlying
      dynamics of the tumor by an LDS and used the system parameters to segment the
      carcinoma on the DCE-MRI. Twenty-four patients with biopsy-proven IDCs were
      analyzed. The lesions segmented by the algorithm were compared with an expert
      radiologist's segmentation and the output of a commercial software, CADstream.
      The results are quantified in terms of the accuracy and sensitivity of detecting
      the lesion and the amount of overlap, measured in terms of the Dice similarity
      coefficient (DSC). RESULTS: The segmentation algorithm detected the tumor with
      90% accuracy and 100% sensitivity when compared with the radiologist's
      segmentation and 82.1% accuracy and 100% sensitivity when compared with the
      CADstream output. The overlap of the algorithm output with the radiologist's
      segmentation and CADstream output, computed in terms of the DSC was 0.77 and
      0.72, respectively. The algorithm also shows robust stability to imaging noise.
      Simulated imaging noise with zero mean and standard deviation equal to 25% of the
      base signal intensity was added to the DCE-MRI series. The amount of overlap
      between the tumor maps generated by the LDS-based algorithm from the noisy and
      original DCE-MRI was DSC = 0.95. CONCLUSION: The time-series analysis based
      segmentation algorithm provides high accuracy and sensitivity in delineating the
      regions of enhanced perfusion corresponding to tumor from DCE-MRI.

PMID- 24115176
TI  - Using a consensus approach based on the conservation of inter-residue contacts to
      rank CAPRI models.
AB  - Herein we propose the use of a consensus approach, CONSRANK, for ranking CAPRI
      models. CONSRANK relies on the conservation of inter-residue contacts in the
      analyzed decoys ensemble. Models are ranked according to their ability to match
      the most frequently observed contacts. We applied CONSRANK to 19 CAPRI protein
      protein targets, covering a wide range of prediction difficulty and involved in a
      variety of biological functions. CONSRANK results are consistently good, both in
      terms of native-like (NL) solutions ranked in the top positions and of values of
      the Area Under the receiver operating characteristic Curve (AUC). For targets
      having a percentage of NL solutions above 3%, an excellent performance is found,
      with AUC values approaching 1. For the difficult target T46, having only 3.4% NL
      solutions, the number of NL solutions in the top 5 and 10 ranked positions is
      enriched by a factor 30, and the AUC value is as high as 0.997. AUC values below
      0.8 are only found for targets featuring a percentage of NL solutions within
      1.1%. Remarkably, a false consensus emerges only in one case, T42, which happens
      to be an artificial protein, whose assembly details remain uncertain, based on
      controversial experimental data. We also show that CONSRANK still performs very
      well on a limited number of models, provided that more than 1 NL solution is
      included in the ensemble, thus extending its applicability to cases where few
      dozens of models are available.

PMID- 24115177
TI  - Analysis of paspalic acid, lysergic acid, and iso-lysergic acid by capillary zone
      electrophoresis with UV- and quadrupole time-of-flight mass spectrometric
      detection.
AB  - CZE was investigated for separation of lysergic, iso-lysergic, and paspalic acid.
      BGEs were optimized regarding separation selectivity and analysis time as well as
      MS compatibility. BGEs using asparagine, Na-tetraborate, or ammonium acetate
      yielded satisfactory resolution when 40% of methanol was added and the pH
      adjusted to 8.3. Applying acidic BGEs also allowed fast separations but the poor
      stability under acidic conditions of the selected analytes prevented further use.
      With ultraviolet (UV) detection, LODs were 0.45 and 0.40 mg/L for paspalic acid
      and lysergic acid, respectively. Run-to-run precision of peak areas was 1.8% for
      lysergic acid and 1.9% for paspalic acid and day-to-day precision was 2.4 and
      4.0%, respectively. When MS detection was used LODs improved to 0.09 mg/L for
      paspalic acid and 0.07 mg/L for lysergic acid. Repeatability results were
      excellent for a CZE-MS method without internal standard ranging from 3.4% for the
      highest standard concentration to 5.8% for the lowest concentration. Recovery and
      matrix effects were studied with samples taken from different stages of the
      manufacturing process and yielded an average recovery of 100.8% and a RSD of
      5.7%. 

PMID- 24115178
TI  - Persistent tracheostomy after primary chemoradiation for advanced laryngeal or
      hypopharyngeal cancer.
AB  - BACKGROUND: Despite the demonstrated survival equivalence between chemoradiation
      and ablative surgery as primary treatment for advanced laryngeal and
      hypopharyngeal cancers, a subset of patients who undergo organ-preservation
      therapy have persistent tracheostomy requirement after completion of treatment.
      METHODS: Patients who received primary chemoradiation for advanced laryngeal or
      hypopharyngeal cancer in a 3-year interval were identified. Rate of persistent
      posttreatment tracheostomy requirement was evaluated. The 12-month overall
      mortality rate was compared between patients who did and did not receive a
      tracheostomy before treatment. RESULTS: In 60 patients identified for this study,
      T3/T4 status and hemilarynx fixation at the time of presentation were associated
      with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022;
      p < .001; and p = .032; p = .0495, respectively). Twelve-month mortality was
      higher in T3/T4 patients who received pretreatment tracheostomy (p = .034).
      CONCLUSION: Patients with advanced laryngeal or hypopharyngeal cancer who require
      tracheostomy before treatment have low rates of decannulation and higher short
      term mortality than those who do not require tracheostomy before organ
      preservation therapy.

PMID- 24115179
TI  - Cerebral small vessel disease affects white matter microstructure in mild
      cognitive impairment.
AB  - Microstructural white matter deterioration is a frequent finding in mild
      cognitive impairment (MCI), potentially underlying default mode network (DMN)
      dysfunctioning. Thus far, microstructural damage in MCI has been attributed to
      Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the
      role of cerebral small vessel disease (CSVD), received less interest. Here, we
      used diffusion tensor imaging (DTI) to examine the role of CSVD in
      microstructural deterioration within the normal appearing white matter (NAWM) in
      MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31)
      macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural
      integrity comparisons within the whole brain NAWM. Secondly, we segmented white
      matter tracts interconnecting DMN brain regions by means of automated
      tractography segmentation. We used NAWM DTI measures from these tracts as
      dependent variables in a stepwise-linear regression analysis, with structural and
      demographical predictors. Our results indicated microstructural deterioration
      within the anterior corpus callosum, internal and external capsule and
      periventricular white matter in MCI patients with CSVD, while in MCI patients
      without CSVD, deterioration was restricted to the right perforant path, a tract
      along the hippocampus. Within the full cohort of MCI patients, microstructure
      within the NAWM of the DMN fiber tracts was affected by the presence of CSVD.
      Within the cingulum along the hippocampal cortex we found a relationship between
      microstructural integrity and ipsilateral hippocampal volume and the extent of
      white matter hyperintensity. In conclusion, we found evidence of CSVD-related
      microstructural damage in fiber tracts subserving the DMN in MCI.

PMID- 24115180
TI  - Liver regeneration by stem/progenitor cells.
AB  - The liver is renowned for its strong, robust regenerative capacity, employing
      different modes of regeneration according to type and extent of injury. The
      process of compensatory hypertrophy of the liver upon partial hepatectomy has
      been standing as a classical model for studying organ regeneration in mammals and
      a subject of exhaustive analyses. Meanwhile, in view of the physiological
      relevance for many of the human liver pathologies induced upon toxic insults or
      hepatitis, other injury models have recently drawn increasing attention. In those
      damaged livers where hepatocyte proliferation is compromised, adult liver
      stem/progenitor cells (LPCs) are activated and differentiate to hepatocytes and
      cholangiocytes, leading to functional recovery of the organ. Here, we summarize
      and discuss recent findings on the mechanisms underlying the regeneration process
      of the liver. Whereas the primary focus of this article is on those related to
      LPC-mediated regeneration, we also introduce topics on compensatory hypertrophy,
      where application of new technologies and molecular genetics approaches in mice
      has gained a paradigm shift. Identification of various markers for LPC
      populations has expedited their characterization and enabled us to examine their
      differentiation potential in vivo using genetic lineage-tracing approaches.
      Comprehensive studies regarding intercellular signaling pathways and their modes
      of action have succeeded in elucidating novel frameworks for the LPC-niche
      interaction functioning in the regenerating liver. CONCLUSION: Advancing our
      understanding of the cellular and molecular mechanisms for liver regeneration
      should provide a basis for developing therapeutic strategies to treat patients
      with liver disease.

PMID- 24115181
TI  - The seasonal timing of warming that controls onset of the growing season.
AB  - Forecasting how global warming will affect onset of the growing season is
      essential for predicting terrestrial productivity, but suffers from conflicting
      evidence. We show that accurate estimates require ways to connect discrete
      observations of changing tree status (e.g., pre- vs. post budbreak) with
      continuous responses to fluctuating temperatures. By coherently synthesizing
      discrete observations with continuous responses to temperature variation, we
      accurately quantify how increasing temperature variation accelerates onset of
      growth. Application to warming experiments at two latitudes demonstrates that
      maximum responses to warming are concentrated in late winter, weeks ahead of the
      main budbreak period. Given that warming will not occur uniformly over the year,
      knowledge of when temperature variation has the most impact can guide prediction.
      Responses are large and heterogeneous, yet predictable. The approach has
      immediate application to forecasting effects of warming on growing season length,
      requiring only information that is readily available from weather stations and
      generated in climate models. 

PMID- 24115182
TI  - Oil and oil dispersant do not cause synergistic toxicity to fish embryos.
AB  - Atlantic herring (Clupea harengus) embryos were exposed to water accommodated
      fractions (WAFs; oil dissolved in water) and chemically enhanced water
      accommodated fractions (CEWAFs; oil dispersed in water with Corexit 9500A) of
      Medium South American (MESA) crude oil. The CEWAF was approximately 100-fold more
      toxic than WAF based on nominal loadings of test solutions (% v/v). In contrast,
      the ratio of WAF and CEWAF toxicity expressed as measured oil concentrations
      approximated 1.0, indicating that the higher toxicity of CEWAFs was caused by an
      increase in exposure to hydrocarbons with chemical dispersion. In a second
      experiment, the chronic toxicity of Corexit 9500A and chemically dispersed heavy
      fuel oil 7102 (HFO 7102) to rainbow trout (Oncorhynchus mykiss) embryos was
      compared to chemically dispersed Nujol, a nontoxic mineral oil. Dispersant alone
      was toxic, but caused different signs of toxicity than HFO 7102. Nujol at a
      dispersant-to-oil ratio of 1:20 was nontoxic, suggesting that dispersant was
      sequestered by oil and not present at toxic concentrations. In contrast, the same
      nominal loadings of dispersed HFO 7102 caused concentration-dependent increases
      in toxicity. Both experiments suggest that chemically dispersed oil was more
      toxic to fish embryos than solutions created by mechanical mixing due to the
      increased exposure of fish to petroleum hydrocarbons and not to changes in
      hydrocarbon toxicity. The Nujol control discriminated between the toxicity of oil
      and chemical dispersant and would be a practical addition to programs of
      dispersant testing.

PMID- 24115183
TI  - Voice quality after treatment of T1a glottic cancer.
AB  - OBJECTIVES/HYPOTHESIS: To compare voice handicap and quality of life after
      radiotherapy (RT) versus transoral laser surgery (LS) for T1a glottic carcinoma.
      STUDY DESIGN: Retrospective study (1996-2011) of patients treated with RT or LS
      for T1a glottic squamous cell carcinoma with curative intent. METHODS: Disease
      free patients were assessed using Voice Handicap Index (VHI 30) and European
      Organization for Research and Treatment of Cancer Head and Neck Quality of Life
      (EORTC QLQ-HN35) questionnaires. RESULTS: Of 147 patients, 95 (65%) completed the
      questionnaires: fifty-one patients an average of 8 years after RT and 44 patients
      an average of 4 years after LS (no difference in age or sex ratio). The average
      total VHI 30 was 13.1 for RT and 29.2 for LS (P < .0001), with average emotional,
      physical and functional subscores significantly different. The average total
      EORTC QLQ-HN35 was 37.7 for RT versus 40.7 for LS (P = .7), with a difference
      only in the speaking subscore (P = .04). CONCLUSIONS: Long-term subjective voice
      related quality of life was worse after LS, with no difference in other domains.
      These results should be interpreted in light of the biases inherent in
      retrospective studies. LEVEL OF EVIDENCE: 4.

PMID- 24115184
TI  - Effects of calcium and vitamin D supplementation on crypt morphology in normal
      colon mucosa: A randomized clinical trial.
AB  - Calcium and vitamin D modify the molecular phenotypic profiles of colon crypts in
      the normal colorectal mucosa of colorectal adenoma patients, but their effects on
      crypt morphology (length, perimeter, and area) are unknown. We analyzed data from
      a previously conducted pilot, randomized, double-blind, placebo-controlled 2 * 2
      factorial chemoprevention clinical trial of supplemental calcium 2000 mg/d and
      vitamin D3 800 IU/d, alone and in combination, versus placebo over 6 mo.
      Colorectal crypt length, perimeter, and area in the normal-appearing rectal
      mucosa were quantified by image analysis. The mean crypt length increased by 1%
      (P=0.92) in the calcium group, and decreased by 2% (P=0.69) and 4% (P=0.40) in
      the vitamin D and calcium plus vitamin D groups, respectively, relative to the
      placebo group. The mean crypt perimeter decreased by 2% (P=0.70) and 4% (P=0.40)
      in the vitamin D and calcium plus vitamin D groups, respectively, relative to the
      placebo group, but did not change appreciably in the calcium group. The mean
      crypt area decreased by 2% (P=0.74), 5% (P=0.41) and 7% (P=0.30) in the calcium,
      vitamin D and calcium plus vitamin D groups, respectively, relative to the
      placebo group. Calcium and/or vitamin D3 supplementation do not appear to
      appreciably change crypt morphology in the normal colorectal mucosa of sporadic
      adenoma patients. These results, taken together with previous findings, support
      the use of molecular phenotypic over morphologic pre-neoplastic biomarkers of
      risk for colorectal neoplasms.

PMID- 24115185
TI  - The brief aggression questionnaire: psychometric and behavioral evidence for an
      efficient measure of trait aggression.
AB  - A key problem facing aggression research is how to measure individual differences
      in aggression accurately and efficiently without sacrificing reliability or
      validity. Researchers are increasingly demanding brief measures of aggression for
      use in applied settings, field studies, pretest screening, longitudinal, and
      daily diary studies. The authors selected the three highest loading items from
      each of the Aggression Questionnaire's (Buss & Perry, 1992) four subscales-
      Physical Aggression, Verbal Aggression, anger, and hostility--and developed an
      efficient 12-item measure of aggression--the Brief Aggression Questionnaire
      (BAQ). Across five studies (N = 3,996), the BAQ showed theoretically consistent
      patterns of convergent and discriminant validity with other self-report measures,
      consistent four-factor structures using factor analyses, adequate recovery of
      information using item response theory methods, stable test-retest reliability,
      and convergent validity with behavioral measures of aggression. The authors
      discuss the reliability, validity, and efficiency of the BAQ, along with its many
      potential applications.

PMID- 24115187
TI  - Bacterial succession and degradative changes by biofilm on plastic medium for
      wastewater treatment.
AB  - Biofilms contain a diverse range of microorganisms and their varying
      extracellular polysaccharides. The present study has revealed biofilm succession
      associated with degradative effects on plastic (polypropylene) and contaminants
      in sludge. The wet weight of biofilm significantly (p < 0.05) increased; from
      0.23 +/- 0.01 to 0.44 +/- 0.01 g. Similarly, the dry weight of the biofilm
      increased from 0.02 to 0.05 g. Significant reduction in pathogens (E. coli and
      feacal coliforms) by MPN technique (>80%) and in chemical parameters (decrease in
      COD, BOD5 of 73.32 and 69.94%) representing diminution of organic pollutants.
      Energy dispersive X-ray spectroscopy (EDS) of plastic revealed carbon and oxygen
      contents, further surface analysis of plastic by scanning electron microscopy
      (SEM) revealed emergence of profound bacterial growth on the surface. Fourier
      transform infrared (FTIR) spectroscopy conforms its biotransformation under
      aerobic conditions after 8 weeks. New peaks developed at the region 1050 and 969
      cm(-1) indicating CO and CC bond formation. Thus plastic with 6 weeks old aerobic
      biofilm (free of pathogens, max. weight, and OD, efficient COD & BOD removal
      ability) is suggested to be maintained in fixed biofilm reactors for wastewater
      treatment.

PMID- 24115186
TI  - Increased expression of putative cancer stem cell markers in the bone marrow of
      prostate cancer patients is associated with bone metastasis progression.
AB  - BACKGROUND: The number of cells positive for the alpha-6 and alpha-2 integrin
      subunits and the c-Met receptor in primary tumors and bone biopsies from prostate
      cancer patients has been correlated with metastasis and disease progression. The
      objective of this study was to quantify disseminated tumour cells present in bone
      marrow in prostate cancer patients using specific markers and determine their
      correlation with metastasis and survival. METHODS: Patients were included at
      different stage of prostate cancer disease, from localised to metastatic
      castration-resistant prostate cancer. Healthy men were used as a control group.
      Bone marrow samples were collected and nucleated cells separated. These were
      stained for CD45, alpha-2, alpha-6 integrin subunits and c-Met and samples were
      processed for analysis and quantification of CD45-/alpha2+/alpha6+/c-met + cells
      using flow cytometry. Clinical and pathological parameters were assessed and
      survival measured. Statistical analyses were made of associations between disease
      specific parameters, bone marrow flow cytometry data, prostate-specific antigen
      (PSA) progression free survival and bone metastases progression free survival.
      RESULTS: For all markers, the presence of more than 0.1% positive cells in bone
      marrow aspirates was significantly associated with the risk of biochemical
      progression, the risk of developing metastasis and death from prostate cancer.
      CONCLUSIONS: Quantification of cells carrying putative stem cell markers in bone
      marrow is a potential indicator of disease progression. Functional studies on
      isolated cells are needed to show more specifically their property for metastatic
      spread in prostate cancer.

PMID- 24115188
TI  - Augmentation of fluoxetine with lovastatin for treating major depressive
      disorder, a randomized double-blind placebo controlled-clinical trial.
AB  - BACKGROUNDS: There are contradictory evidence about the effect of statins on
      depression. This 6-week-randomized placebo-controlled clinical trial assessed the
      efficacy and safety of lovastatin as an adjuvant agent for treating major
      depressive disorder (MDD). METHODS: The participants were 68 patients with MDD
      according to DSM-IV diagnostic criteria. The sample was randomly allocated into
      fluoxetine (up to 40 mg/day) plus lovastatin (30 mg/day) group or fluoxetine plus
      placebo group. Hamilton Depression Rating scale was used to measure depression
      score at baseline, week 2, and week 6. RESULTS: Both groups showed a significant
      decrease of depression score on the Hamilton Depression scale. However, the
      treatment group decreased depression score more than placebo group [12.8(6.3) vs.
      8.2(4.0), t = 3.4, df = 60, P < .001]. Any serious adverse effect was not found.
      DISCUSSION: These results suggest that lovastatin as an adjuvant treatment may be
      effective for treating patients with MDD.

PMID- 24115189
TI  - The search for the optimal anabolic osteoporosis therapy.

PMID- 24115190
TI  - Spiral-type heteropolyhedral coordination network based on single-crystal
      LiSrPO4: implications for luminescent materials.
AB  - Novel structures of luminescent materials, which are used as light sources for
      next-generation illumination, are continuously being improved for use in white
      light-emitting diodes. Activator-doped known structures are reported as habitual
      down-conversion phosphors in solid-state lightings and displays. Consequently,
      the intrinsic qualities of the existent compounds produce deficiencies that limit
      their applications. Herein we report a spiral-network single-crystal
      orthophosphate (LiSrPO4) prepared in a platinum crucible with LiCl flux through
      crystal-growth reactions of SrCl2 and Li3PO4 in air. It crystallizes in a
      hexagonal system with a=5.0040(2) and c=24.6320(16) A, V=534.15(5) A(3), and Z=6
      in the space group P6(5). The unit cell is comprised of LiO4 and PO4 tetrahedrons
      that form a three-dimensional LiPO4(2-) anionic framework with a helical channel
      structure along the c axis in which the Sr(2+) cation is accommodated. The
      optical band gap of this composition is about 3.65 eV, as determined by using
      UV/Vis absorption and diffuse reflection spectra. We used the crystal-growth
      method to synthesize blue- and red-emitting crystals that exhibited pure color,
      low reabsorption, a large Stokes shift, and efficient conversion of ultraviolet
      excitation light into visible light. Emphasis was placed on the development of
      gratifying structure-related properties of rare-earth luminescent materials and
      their applications.

PMID- 24115191
TI  - Development of a method for urine bikunin/urinary trypsin inhibitor (UTI)
      quantitation and structural characterization: Application to type 1 and type 2
      diabetes.
AB  - Bikunin is a plasma proteinase inhibitor often associated with inflammatory
      conditions. It has a half-life of few minutes and it is rapidly excreted into
      urine as urinary trypsin inhibitor (UTI). UTI levels are usually low in healthy
      individuals but they can increase up to tenfold in both acute and chronic
      inflammatory diseases. This article describes a sensitive method for both direct
      UTI quantitation and structural characterization. UTI purification was performed
      by anion exchange micro-chromatography followed by SDS-PAGE. A calibration curve
      for protein quantitation was set up by using a purified UTI fraction. UTI
      identification and structural characterization was performed by Nano-LC-MS/MS
      analysis. The method was applied on urine samples from 9 patients with type 1
      diabetes, 11 patients with type 2 diabetes, and 28 healthy controls, matched for
      age and sex with patients, evidencing higher UTI levels in both groups of
      patients with respect to controls (p < 0.001 and p = 0.001, respectively).
      Spearman's correlation tests highlighted no association between UTI levels and
      age in each group tested. Owing to the elevated sensitivity and specificity, the
      described method allows UTI quantitation from very low quantities of specimen.
      Furthermore, as UTI concentration is normalized for creatinine level, the
      analysis could be also performed on randomly collected urine samples. Finally,
      MS/MS analysis prospects the possibility of characterizing PTM sites potentially
      able to affect UTI localization, function, and pathophysiological activity.
      Preliminary results suggest that UTI levels could represent a useful marker of
      chronic inflammatory condition in type 1 and 2 diabetes. 

PMID- 24115192
TI  - Histopathological features of clinical perineural invasion of cutaneous squamous
      cell carcinoma of the head and neck and the potential implications for treatment.
AB  - BACKGROUND: Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most
      commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN).
      The cranial nerves are a conduit for skin cancer to reach the brainstem. METHODS:
      The histopathological features of 51 tissue specimens from 49 patients with
      cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and
      longitudinal sections. RESULTS: No skip lesions were identified. Tumor spread was
      contiguous in all specimens. No tumor spread into the perineural space from
      surrounding or adjacent tumor was seen. Proximal large cranial nerves showed
      epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and
      intraneural invasion. CONCLUSION: Perineural tumor spread in cutaneous SCCHN was
      contiguous and no skip lesions were evident in nerve specimens assessed in this
      series. Spread beyond cranial nerve perineurium was uncommon, reflecting its
      multilayer barrier function at this level. These findings may have treatment
      implications.

PMID- 24115193
TI  - Alternative complement pathway activation products in urine and kidneys of
      patients with ANCA-associated GN.
AB  - BACKGROUND AND OBJECTIVES: Previous study revealed that complement activation
      products of the alternative pathway could be detected in renal specimens of human
      ANCA-associated vasculitis. The current study aimed to investigate the clinical
      and pathologic significance of complement activation products in the urine and
      kidneys of patients with ANCA-associated vasculitis. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Renal biopsy specimens from 29 patients with ANCA
      associated vasculitis diagnosed at Peking University First Hospital from January
      of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29
      patients in active stage and 22 ANCA-associated vasculitis patients in complete
      remission who were independent of the above-mentioned 29 patients were collected.
      Urine samples from 28 patients with lupus nephritis and 25 healthy individuals
      were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by
      immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were
      determined by ELISA. RESULTS: The deposition, measured by the mean optical
      density of Bb, which is an alternative complement pathway marker, in glomeruli
      correlated with the proportion of total crescents (r=0.50, P=0.006), the extent
      of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45,
      P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely
      with the proportion of normal glomeruli (r=-0.49, P=0.008). The urinary levels of
      Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared
      with remission stage. The urinary levels of Bb in patients with active ANCA
      associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and
      correlated inversely with the proportion of normal glomeruli in renal specimens
      (r=-0.49, P=0.009). CONCLUSIONS: The present study provides additional evidence
      that complement activation through the alternative pathway occurred in the
      development of ANCA-associated vasculitis. The renal deposition of Bb and urinary
      Bb levels were associated with the severity of renal injury.

PMID- 24115195
TI  - Differences in access to kidney transplantation between Hispanic and non-Hispanic
      whites by geographic location in the United States.
AB  - BACKGROUND AND OBJECTIVES: Hispanic patients undergoing chronic dialysis are less
      likely to receive a kidney transplant compared with non-Hispanic whites. This
      study sought to elucidate disparities in the path to receipt of a deceased donor
      transplant between Hispanic and non-Hispanic whites. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Using the US Renal Data System, 417,801 Caucasians
      who initiated dialysis between January 1, 1995 and December 31, 2007 with follow
      up through 2008 were identified. This study investigated time from first dialysis
      to first kidney transplantation, time from first dialysis to waitlisting, and
      time from waitlisting to kidney transplantation. Multivariable Cox regression
      estimated cause-specific hazard ratios (HRCS) and subdistribution (competing
      risk) hazard ratios (HRSD) for Hispanics versus non-Hispanic whites. RESULTS:
      Hispanics experienced lower adjusted rates of deceased donor kidney
      transplantation than non-Hispanic whites (HRCS, 0.77; 95% confidence interval
      [95% CI], 0.75 to 0.80) measured from dialysis initiation. No meaningful
      differences were found in time from dialysis initiation to placement on the
      transplant waitlist. Once waitlisted, Hispanics had lower adjusted rates of
      deceased donor kidney transplantation (HRCS, 0.66; 95% CI, 0.64 to 0.68), and the
      association attenuated once accounting for competing risks (HRSD, 0.79; 95% CI,
      0.77 to 0.81). Additionally controlling for blood type and organ procurement
      organization further reduced the disparity (HRSD, 0.99; 95% CI, 0.96 to 1.02).
      CONCLUSIONS: After accounting for geographic location and controlling for
      competing risks (e.g., Hispanic survival advantage), the disparity in access to
      deceased donor transplantation was markedly attenuated among Hispanics compared
      with non-Hispanic whites. To overcome the geographic disparities that Hispanics
      encounter in the path to transplantation, organ allocation policy revisions are
      needed to improve donor organ equity.

PMID- 24115194
TI  - Cutaneous manifestations of ESRD.
AB  - A broad range of skin diseases occurs in patients with ESRD: from the benign and
      asymptomatic to the physically disabling and life-threatening. Many of them
      negatively impact on quality of life. Their early recognition and treatment are
      essential in reducing morbidity and mortality. The cutaneous manifestations can
      be divided into two main categories: nonspecific and specific. The nonspecific
      manifestations are commonly seen and include skin color changes, xerosis, half
      and-half nails, and pruritus. The specific disorders include acquired perforating
      dermatosis, bullous dermatoses, metastatic calcification, and nephrogenic
      systemic fibrosis. This review article describes these conditions and considers
      the underlying pathophysiology, clinical presentations, diagnosis, and treatment
      options. 

PMID- 24115196
TI  - Racial and socioeconomic disparities in the allocation of expanded criteria donor
      kidneys.
AB  - BACKGROUND AND OBJECTIVES: In carefully selected individuals, receiving expanded
      criteria donor (ECD) kidneys confer a survival advantage over remaining on
      dialysis. However, wait lists for ECD kidneys often include a significant
      proportion of young patients, who have no predictable survival benefit from ECD
      kidneys. This study hypothesized that educational and socioeconomic factors might
      influence a younger patient's decision to accept an ECD kidney. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study was a retrospective analysis of all
      first single-kidney transplants in the Scientific Registry of Transplant
      Recipients database from 2000 to 2009 in patients aged 18-40 years and waitlisted
      <3 years. The primary outcome measured was the odds of receiving an ECD kidney
      compared with an standard criteria donor kidney in different demographic
      subgroups. Race, income, and education were analyzed in main-effect and two-way
      interaction models, corrected for candidate panel reactive antibodies and sex.
      RESULTS: Of 13,615 ECD transplants, 591 kidneys (4.3%) went to recipients aged
      between 18 and 40 years who were waitlisted <3 years. African Americans (odds
      ratio, 1.71; 95% confidence interval, 1.26 to 2.33) or those with low education
      (odds ratio, 2.32; 95% confidence interval, 1.38 to 3.89) were more likely to
      receive an ECD kidney than Caucasians or those with a college degree,
      respectively. However, African Americans with higher education levels did not
      have significantly higher odds of receiving an ECD kidney than Caucasians with a
      college degree. CONCLUSIONS: In patients aged <40 years and waitlisted <3 years,
      African Americans and those with lower educational status and low income are more
      likely to receive an ECD kidney than Caucasians or those with higher education.
      It is important that health care providers and patients understand such
      disparities to facilitate a more rational use of ECD kidneys.

PMID- 24115197
TI  - Ethics and health policy of dialyzing a patient in a persistent vegetative state.
AB  - Each year, out-of-hospital cardiac arrests occur in approximately 300,000
      Americans. Of these patients, less than 10% survive. Survivors often live with
      neurologic impairments that neurologists classify as anoxic-ischemic
      encephalopathy (AIE). Neurologic impairments under AIE can vary widely, each with
      unique outcomes. According to the American Academy of Neurology Practice
      Parameter paper, the definition of poor outcome in AIE includes death, persistent
      vegetative state (PVS), or severe disability requiring full nursing care 6 months
      after event. In a recent survey, participants deemed an outcome of PVS as "worse
      than dead." Lay persons' assessments of quality of life for those in a PVS
      provide assistance for surrogate decision-makers who are confronted with the
      clinical decision-making for a loved one in a PVS, whereas clinical practice
      guidelines help health care providers to make decisions with patients and/or
      families. In 2000, the Renal Physicians Association and the American Society of
      Nephrology published a clinical practice guideline, "Shared Decision-Making in
      the Appropriate Initiation of and Withdrawal from Dialysis." In 2010, after
      advances in research, a second edition of the guideline was published. The
      updated guideline confirmed the recommendation to withhold or withdraw ongoing
      dialysis in "patients with irreversible, profound neurological impairments such
      that they lack signs of thought, sensation, purposeful behavior and awareness of
      self and environment," such as found in patients with PVS. Here, the authors
      discuss the applicability of this guideline to patients in a PVS. In addition,
      they build on the guideline's conception of shared decision-making and discuss
      how continued dialysis violates ethical and legal principles of care in patients
      in a PVS. 

PMID- 24115199
TI  - Organic chemistry of graphene: the Diels-Alder reaction.
AB  - Herein, by using dispersion-corrected density functional theory, we investigated
      the Diels-Alder chemistry of pristine and defective graphene. Three dienes were
      considered, namely 2,3-dimethoxy-1,3-butadiene (DMBD), 9-methylanthracene (9MA),
      and 9,10-dimethylanthracene (910DMA). The dienophiles that were assayed were
      tetracyanoethylene (TCNE) and maleic anhydride (MA). When pristine graphene acted
      as the dienophile, we found that the cycloaddition products were 47-63 kcal mol(
      1) less stable than the reactants, thus making the reaction very difficult. The
      presence of Stone-Wales translocations, 585 double vacancies, or 555-777
      reconstructed double vacancies did not significantly improve the reactivity
      because the cycloaddition products were still located at higher energy than the
      reactants. However, for the addition of 910DMA to single vacancies, the product
      showed comparable stability to the separated reactants, whereas for unsaturated
      armchair edges the reaction was extremely favorable. With regards the reactions
      with dienophiles, for TCNE, the cycloaddition product was metastable. In the case
      of MA, we observed a reaction product that was less stable than the reactants by
      50 kcal mol(-1) . For the reactions between graphene as a diene and the
      dienophiles, we found that the most-promising defects were single vacancies and
      unsaturated armchair edges, because the other three defects were much-less
      reactive. Thus, we conclude that the reactions with these above-mentioned dienes
      may proceed on pristine or defective sheets with heating, despite being
      endergonic. The same statement also applies to the dienophile maleic anhydride.
      However, for TCNE, the reaction is only likely to occur onto single vacancies or
      unsaturated armchair edges. We conclude that the dienophile character of graphene
      is slightly stronger than its behavior as a diene. 

PMID- 24115198
TI  - Intrinsically disordered regions in autophagy proteins.
AB  - Autophagy is an essential eukaryotic pathway required for cellular homeostasis.
      Numerous key autophagy effectors and regulators have been identified, but the
      mechanism by which they carry out their function in autophagy is not fully
      understood. Our rigorous bioinformatic analysis shows that the majority of key
      human autophagy proteins include intrinsically disordered regions (IDRs), which
      are sequences lacking stable secondary and tertiary structure; suggesting that
      IDRs play an important, yet hitherto uninvestigated, role in autophagy. Available
      crystal structures corroborate the absence of structure in some of these
      predicted IDRs. Regions of orthologs equivalent to the IDRs predicted in the
      human autophagy proteins are poorly conserved, indicating that these regions may
      have diverse functions in different homologs. We also show that IDRs predicted in
      human proteins contain several regions predicted to facilitate protein-protein
      interactions, and delineate the network of proteins that interact with each
      predicted IDR-containing autophagy protein, suggesting that many of these
      interactions may involve IDRs. Lastly, we experimentally show that a BCL2
      homology 3 domain (BH3D), within the key autophagy effector BECN1 is an IDR. This
      BH3D undergoes a dramatic conformational change from coil to alpha-helix upon
      binding to BCL2s, with the C-terminal half of this BH3D constituting a binding
      motif, which serves to anchor the interaction of the BH3D to BCL2s. The
      information presented here will help inform future in-depth investigations of the
      biological role and mechanism of IDRs in autophagy proteins.

PMID- 24115200
TI  - Predicting wear and blood metal ion levels in metal-on-metal hip resurfacing.
AB  - Suboptimal component position and design are thought to lead to edge wear and
      raised blood metal ion levels in metal-on-metal hip resurfacing (MOM-HR). These
      factors are thought to influence the "contact patch to rim distance" (CPRD), and
      calculation of this distance may improve prediction of wear and blood metal ion
      levels. We measured blood cobalt and chromium ion levels and the wear rates of
      the bearing surfaces in 165 MOM-HR retrieval cases. We then determined the
      contribution and effect sizes of cup inclination and version angles, component
      size and design, and CPRD (calculated from case-specific data) on blood metal ion
      levels and component wear rates. Acetabular orientation explained between 16.3%
      and 28.5% of the variation in wear rates and metal ion levels, whereas component
      size and design explained between 7.3% and 21.8% of the variability. In
      comparison, CPRD explained up to 67.7% of the variability, significantly greater
      than any other variable (all p < 0.0001). CPRD is a good predictor of wear and
      improves our understanding of wear performance and the mechanisms leading to edge
      loading.

PMID- 24115201
TI  - Polyacrylonitrile block copolymers for the preparation of a thin carbon coating
      around TiO2 nanorods for advanced lithium-ion batteries.
AB  - Herein, a new method for the realization of a thin and homogenous carbonaceous
      particle coating, made by carbonizing RAFT polymerization derived block
      copolymers anchored on anatase TiO2 nanorods, is presented. These block
      copolymers consist of a short anchor block (based on dopamine) and a long, easily
      graphitizable block of polyacrylonitrile. The grafting of such block copolymers
      to TiO2 nanorods creates a polymer shell, which can be visualized by atomic force
      microscopy (AFM). Thermal treatment at 700  degrees C converts the
      polyacrylonitrile block to partially graphitic structures (as determined by Raman
      spectroscopy), establishing a thin carbon coating (as determined by transmission
      electron microscopy, TEM, analysis). The carbon-coated TiO2 nanorods show
      improved electrochemical performance in terms of achievable specific capacity
      and, particularly, long-term cycling stability by reducing the average capacity
      fading per cycle from 0.252 mAh g(-1) to only 0.075 mAh g(-1) . 

PMID- 24115202
TI  - Functional activity and effective connectivity of the posterior medial prefrontal
      cortex during processing of incongruent mental states.
AB  - The neurocognitive components of Theory of Mind reasoning remain poorly
      understood. In particular the role of the posterior medial prefrontal cortex in
      the processing of other's mental states such as beliefs that are incongruent with
      one's own knowledge of reality is not clear-cut. It is unknown whether this
      region is involved in computing discrepant mental states or in subsequently
      resolving a response conflict between the discrepant others' and one's own
      beliefs. To test this, we adapted a false belief paradigm for the separate
      inspection of functional brain activity related to (1) the computation of
      diverging beliefs and (2) the subsequent consideration and selection of another's
      or one's own belief. Based on statistical parametric findings from functional
      neuroimaging, we employed dynamic causal modelling combined with Bayesian model
      selection to further characterize the interplay of resulting brain regions. In
      the initial computation of diverging beliefs, the posterior medial prefrontal
      cortex (pMPFC) and the bilateral temporoparietal cortex were crucially involved.
      The findings suggest that the bilateral temporal cortex engages in the
      construction and adjustment of diverging mental states by encoding relevant
      environmental information. The pMPFC inhibits this stimulus-bound processing
      which helps to compute discrepant mental states and process another's false
      belief decoupled from one's own perception of reality. In the subsequent question
      phase the right temporoparietal cortex showed increased activity related to
      switching to and reconsidering another's beliefs in order to select the correct
      response.

PMID- 24115203
TI  - Effects of silver nanoparticles on soil enzyme activities with and without added
      organic matter.
AB  - The effects of silver nanoparticles (AgNPs) on terrestrial ecosystems need to be
      better understood and assessed. Cationic silver (Ag+) has well-documented
      toxicity against bacteria, but it is not clear what will be the effect of
      nanoscale Ag. In the present study, the potential effects of AgNPs were
      investigated in soils by measuring activity of the enzymes phosphomonoesterase,
      arylsulfatase, beta-D-glucosidase, and leucine-aminopeptidase. The toxicity of
      AgNPs was compared with that of ionic Ag, and the ameliorating effects of soil
      organic matter were evaluated. To this end, 2 soils with different organic matter
      contents were artificially contaminated with either AgNPs or Ag-acetate at
      equivalent total Ag concentrations. In general, enzyme activities were inhibited
      as a function of the Ag concentration in the soil. In the AgNP exposures, only a
      small fraction of the AgNP was actually truly dissolved (found in the <1-nm
      fraction), suggesting that the particulate forms of AgNPs resulted in a
      significant inhibition of soil enzymes. The addition of organic matter to the
      soils appeared to enhance enzyme activities; however, the mechanism of organic
      matter action is not clear given that dissolved Ag concentrations were similar in
      both the organic-matter-amended and unamended soils. The present study shows that
      the AgNP produces significant negative effects on the soil enzyme activities
      tested. The Ag chemical speciation measurements suggested that the AgNP caused
      greater toxic effects to the soil enzymes at the low Ag concentrations. For the
      larger concentrations of total soil Ag, causes of the negative effects on enzyme
      activities are less obvious but suggest that colloidal forms of Ag play a role.

PMID- 24115204
TI  - Macrophage plasticity and polarization in liver homeostasis and pathology.
AB  - Resident and recruited macrophages are key players in the homeostatic function of
      the liver and in its response to tissue damage. In response to environmental
      signals, macrophages undergo polarized activation to M1 or M2 or M2-like
      activation states. These are extremes of a spectrum in a universe of activation
      states. Progress has been made in understanding the molecular mechanisms
      underlying the polarized activation of mononuclear phagocytes. Resident and
      recruited macrophages are a key component of diverse homeostatic and pathological
      responses of hepatic tissue. Polarized macrophages interact with hepatic
      progenitor cells, integrate metabolic adaptation, mediate responses to infectious
      agents, orchestrate fibrosis in a yin-yang interaction with hepatic stellate
      cells, and are a key component of tumor-promoting inflammation. CONCLUSION: A
      better understanding of macrophage diversity and plasticity in liver homeostasis
      and pathology may pave the way to innovative diagnostic and therapeutic
      approaches.

PMID- 24115205
TI  - Biobanking of derivatives from radical retropubic and robot-assisted laparoscopic
      prostatectomy tissues as part of the prostate cancer biorepository network.
AB  - BACKGROUND: The goal of the Prostate Cancer Biorepository Network (PCBN) is to
      develop a biorepository with high-quality, well-annotated specimens obtained in a
      systematic, reproducible fashion using optimized and standardized protocols, and
      an infrastructure to facilitate the growth of the resource and its wide usage by
      the prostate cancer research community. An emerging area of concern in the field
      of prostate cancer biobanking is an apparent shift in the proportion of surgical
      procedures performed for prostate cancer treatment from radical retropubic
      prostatectomy (RRP) to robot-assisted laparoscopic prostatectomy (RALP). Our
      study aimed to determine the potential impact of the RALP procedure on the
      detection of known prostate cancer biomarkers, and the subsequent suitability of
      RALP-derived specimens for prostate cancer biomarker studies. METHODS: DNA and
      RNA were extracted from RRP and RALP specimens. Quality assessment was conducted
      using spectrophotometric analysis and RNA was analyzed for RNA integrity number
      (RIN) and by real-time reverse-transcription PCR (qRT-PCR) for racemase, hepsin,
      ERG, TMPRSS2-ERG gene fusions, and the microRNAs miR-26a, miR-26b, miR-141, and
      miR-221. RESULTS: We demonstrate that extraction of derivatives from frozen
      tissues from RRP and RALP specimens yields samples of equally high quality as
      assessed by spectrophotometric and RIN analysis. Likewise, expression levels of
      genes analyzed by qRT-PCR did not differ between RRP and RALP-derived tissues.
      CONCLUSIONS: Our studies indicate that samples obtained from RALP specimens may
      be suitable for prostate cancer biomarker studies-an important finding given the
      current shift in surgical procedures for prostate cancer treatment.

PMID- 24115206
TI  - Community composition has greater impact on the functioning of marine
      phytoplankton communities than ocean acidification.
AB  - Ecosystem functioning is simultaneously affected by changes in community
      composition and environmental change such as increasing atmospheric carbon
      dioxide (CO2 ) and subsequent ocean acidification. However, it largely remains
      uncertain how the effects of these factors compare to each other. Addressing this
      question, we experimentally tested the hypothesis that initial community
      composition and elevated CO2 are equally important to the regulation of
      phytoplankton biomass. We full-factorially exposed three compositionally
      different marine phytoplankton communities to two different CO2 levels and
      examined the effects and relative importance (omega(2) ) of the two factors and
      their interaction on phytoplankton biomass at bloom peak. The results showed that
      initial community composition had a significantly greater impact than elevated
      CO2 on phytoplankton biomass, which varied largely among communities. We suggest
      that the different initial ratios between cyanobacteria, diatoms, and
      dinoflagellates might be the key for the varying competitive and thus functional
      outcome among communities. Furthermore, the results showed that depending on
      initial community composition elevated CO2 selected for larger sized diatoms,
      which led to increased total phytoplankton biomass. This study highlights the
      relevance of initial community composition, which strongly drives the functional
      outcome, when assessing impacts of climate change on ecosystem functioning. In
      particular, the increase in phytoplankton biomass driven by the gain of larger
      sized diatoms in response to elevated CO2 potentially has strong implications for
      nutrient cycling and carbon export in future oceans. 

PMID- 24115207
TI  - Optimal b value in diffusion-weighted imaging for differentiation of abdominal
      lesions.
AB  - PURPOSE: To explore the optimal b value in diffusion-weighted imaging (DWI) for
      differentiation of benign and malignant abdominal lesions. MATERIALS AND METHODS:
      A total of 108 consecutive patients (age 60 +/- 12.5 years) with 127
      pathologically confirmed diagnoses of abdominal lesions were included. Single
      shot echoplanar imaging (SH-EPI) DWI (1.5T) with seven b values and eight
      apparent diffusion coefficient (ADC) maps were obtained. The lesions were
      analyzed visually on DWI and ADC maps for benignity/malignity using a 5-point
      scale and by measuring the ADC values and ADC lesion/normal parenchyma ADC ratio.
      ROC analysis was used to evaluate the diagnostic accuracy of ADC for
      differentiating between benign and malignant lesions. Pathology results were the
      reference standard. RESULTS: Differentiation between malignant and benign lesions
      using visual scoring was successful at b values of 600 or higher (sensitivities,
      specificities, and accuracies were 100/93.8/92.5, 84.7/82.6/80.4, and
      94.4/89.7/88.1, respectively, for b600, 800, and 1000). The mean ADC values of
      malignant lesions were significantly lower than those of benign lesions for all b
      value combinations except b0 and 50 s/mm(2) (P = 0.032 for b0 and 50 s/mm(2) , P
      = 0.000 for other b values). The best b-value combination was 0 and 600 s/mm(2)
      and multiple b2. The lesion/normal parenchymal ADC ratio for b600, b1000, and
      multiple b2 better distinguished between benign and malignant lesions.
      CONCLUSION: In DWI, the optimal b value is 600 s/mm(2) ; multiple b values of 600
      s/mm(2) and higher are recommended to differentiate between benign and malignant
      abdominal lesions. The lesion ADC/normal parenchyma ADC ratio is more accurate
      than using lesion ADC only.

PMID- 24115208
TI  - Diverse nodule bacteria were associated with Astragalus species in arid region of
      northwestern China.
AB  - The legume species of Astragalus as traditional Chinese medicine source and
      environmental protection plants showed an extensive distribution in the arid
      region of northwestern China. However, few rhizobia associating with Astragalus
      have been investigated in this region so far. In this study, 78 endophytic
      bacteria were isolated from root nodules of 12 Astragalus species and
      characterized by the PCR-RFLP of 16S rRNA gene and symbiotic genes together with
      the phylogenetic analysis. Results showed that the majority (53%) of isolates are
      non-nodulating Agrobacterium sp. and the rest are Mesorhizobium genomic species
      (41%), Ensifer spp. and Rhizobium gallicum (6%), respectively. Mesorhizobium
      genomic species are broadly distributed in the Astragalus symbioses and most of
      them share similar symbiotic genes. It seems that horizontal gene transfer
      occurred frequently among different genomic species independent of their original
      hosts and sites. Astragalus adsurgens is nodulated by a widely range of rhizobial
      species in the nodulation test, revealing that it could play an important role in
      diversification of Astragalus symbionts and that might be a reason for its wide
      adaptation to diverse environments. 

PMID- 24115209
TI  - Clinical relevance of fatigue as a residual symptom in major depressive disorder.
AB  - Residual symptoms of major depressive disorder (MDD) following treatment are
      increasingly recognized as having a negative impact on the patient because of
      their association with lack of remission, poorer psychosocial functioning, and a
      more chronic course of depression. Although the effects of specific residual
      symptoms have not been as systematically studied, several symptoms, including
      fatigue, sleep disturbance, anxiety, and concentration difficulties, commonly
      occur as part of the residual state in MDD. In particular, the relatively high
      prevalence of residual fatigue suggests that this symptom is not being adequately
      addressed by standard antidepressant therapies. A review of the clinical
      relevance of residual fatigue was undertaken, using the published literature with
      respect to its assessment, neurobiology, and treatment implications. The findings
      of this review suggest that fatigue is highly prevalent as a residual symptom;
      its response to treatment is relatively poor or delayed; and the presence of
      residual fatigue is highly predictive of inability to achieve remission with
      treatment as well as impaired psychosocial functioning. Recognition of the
      significant consequences of residual fatigue should reinforce the need for
      further therapeutic interventions to help reduce the impact of this symptom of
      MDD. 

PMID- 24115210
TI  - Spiropyran photoswitches in the context of DNA: synthesis and photochromic
      properties.
AB  - A new design is presented for the incorporation of spiropyran photoswitches into
      nucleic acids by oligonucleotide solid phase synthesis. This design enables
      interaction of the 6-nitrospirobenzopyran (NitroBIPS) photoswitch with the
      adjacent nucleobases and leaves the photochemical properties of NitroBIPS intact.
      UV/Vis spectroscopy and HPLC revealed that NitroBIPS incorporated into DNA
      consists of up to 40 % merocyanine in its thermal equilibrium and undergoes
      reversible switching between the photoisomeric spiropyran (SP) and merocyanin
      (MC) state by alternating excitation using visible light or heat for at least
      fifteen switching cycles. Exchanging the chromene part of NitroBIPS on the DNA
      level gives access to differently substituted spiropyran derivatives allowing the
      screening for spiropyrans with suitable properties in a straightforward manner.
      Thus, by incorporating the highly hydrolysis-stable pyrido-spiropyran derivative
      PyBIPS pure light-triggered reversible switching of a spiropyran in DNA has been
      realized for the first time. Therefore, this design represents a new useful
      platform for investigating the photochromic behavior of different spiropyran
      photoswitches in a nucleic acid environment and for using spiropyrans to induce
      light- or heat-triggered changes in conformations or in fluorescence quenching
      properties of oligonucleotides. 

PMID- 24115211
TI  - Docking, scoring, and affinity prediction in CAPRI.
AB  - We present the fifth evaluation of docking and related scoring methods used in
      the community-wide experiment on the Critical Assessment of Predicted
      Interactions (CAPRI). The evaluation examined predictions submitted for a total
      of 15 targets in eight CAPRI rounds held during the years 2010-2012. The targets
      represented one the most diverse set tackled by the CAPRI community so far. They
      included only 10 "classical" docking and scoring problems. In one of the
      classical targets, the new challenge was to predict the position of water
      molecules in the protein-protein interface. The remaining five targets
      represented other new challenges that involved estimating the relative binding
      affinity and the effect of point mutations on the stability of designed and
      natural protein-protein complexes. Although the 10 classical CAPRI targets
      included two difficult multicomponent systems, and a protein-oligosaccharide
      complex with which CAPRI participants had little experience, this evaluation
      indicates that the performance of docking and scoring methods has remained quite
      robust. More remarkably, we find that automatic docking servers exhibit a
      significantly improved performance, with some servers now performing on par with
      predictions done by humans. The performance of CAPRI participants in the new
      challenges, briefly reviewed here, was mediocre overall, but some groups did
      relatively well and their approaches suggested ways of improving methods for
      designing binders and for estimating the free energies of protein assemblies,
      which should impact the field of protein modeling and design as a whole.

PMID- 24115213
TI  - RAFT polymerization of 4-vinylphenylboronic acid as the basis for micellar sugar
      sensors.
AB  - Well-defined homo and mPEGylated block (co)polymers of the commercially available
      unprotected 4-vinylphenylboronic acid (4-VBA) monomer are reported based on
      reversible addition-fragmentation chain transfer (RAFT) polymerization. The
      polymerization kinetics are studied in detail for homo and block
      (co)polymerizations with different chain transfer agents (CTAs) to optimize the
      preparation of well-defined polymer structures, eventually leading to
      comparatively low dispersities (D <= 1.25). Subsequently, block (co)polymers with
      methoxy poly(ethylene glycol) mPEG-b-P(4-VBA) are prepared using a mPEG
      functionalized CTA. The formed block copolymer mPEG114 -b-P(4-VBA)30 is
      demonstrated to be pH and glucose responsive as its micellization behavior is
      dictated by pH as well as the presence of glucose. The glucose-responsive pH
      window of mPEG114 -b-P(4-VBA)30 is found to be pH 9-10 based on the DLS and TEM
      measurement. 

PMID- 24115212
TI  - Cyclic AMP regulates the migration and invasion potential of human pancreatic
      cancer cells.
AB  - Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma
      (PDAC) results in poor prognosis and marked lethality. Rho monomeric G protein
      levels are increased in pancreatic cancer tissue. As the mechanisms underlying
      PDAC malignancy are little understood, we investigated the role for cAMP in
      regulating monomeric G protein regulated invasion and migration of pancreatic
      cancer cells. Treatment of PDAC cells with cAMP elevating agents that activate
      adenylyl cyclases, forskolin, protein kinase A (PKA), 6-Bnz-cAMP, or the cyclic
      nucleotide phosphodiesterase inhibitor cilostamide significantly decreased
      migration and Matrigel invasion of PDAC cell lines. Inhibition was dose-dependent
      and not significantly different between forskolin or cilostamide treatment. cAMP
      elevating drugs not only blocked basal migration, but similarly abrogated
      transforming-growth factor-beta-directed PDAC cell migration and invasion. The
      inhibitory effects of cAMP were prevented by the pharmacological blockade of PKA.
      Drugs that increase cellular cAMP levels decreased levels of active RhoA or RhoC,
      with a concomitant increase in phosphorylated RhoA. Diminished Rho signaling was
      correlated with the appearance of thickened cortical actin bands along the
      perimeter of non-motile forskolin or cilostamide-treated cells. Decreased
      migration did not reflect alterations in cell growth or programmed cell death.
      Collectively these data support the notion that increased levels of cAMP
      specifically hinder PDAC cell motility through F-actin remodeling.

PMID- 24115214
TI  - Study on capillaries covalently bound with phospholipid vesicles for open-tubular
      capillary electrochromatography and application to on-line open-tubular capillary
      electrochromatography-mass spectrometry.
AB  - Phospholipid vesicles were covalently attached to iminoaldehyde-coated fused
      silica capillaries and applied to the separation of model steroids by open
      tubular CEC (OT-CEC). The effects of reducing the formed Schiff's base with
      sodium borohydride and of the liposome composition on the stability of the
      coating were investigated. In addition, the studies were focused on the
      optimization of running conditions (pH values and composition of BGE solution)
      when CEC, using capillaries covalently bound with liposome dispersions, was
      coupled to MS. The effect of cholesterol in the liposome dispersion on the
      binding of model analytes was studied, using liposome dispersions comprising
      80/20 mol% zwitterionic 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC)
      and the negatively charged phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho
      L-serine (POPS) and 40/40/20 mol% POPC/POPS/cholesterol. Cholesterol in liposomes
      (greatly) enhanced the stability of the capillaries by making the coatings more
      rigid, resulting in lower retention factors for all the studied model steroids.
      Although most of the studies were carried out by open tubular CEC-UV Vis, the
      applicability of the capillaries to on-line CEC-MS was demonstrated as well. On
      line CEC-MS studies on model steroids proved the suitability of coated
      capillaries for analyte-lipid membrane interaction studies, and especially for
      such analytes that are difficult to detect by conventional on-line UV Vis.

PMID- 24115215
TI  - Superior laryngeal nerve quantitative intraoperative monitoring is possible in
      all thyroid surgeries.
AB  - OBJECTIVES/HYPOTHESIS: To report normative electromyography (EMG) data on the
      external branch of the superior laryngeal nerve (EBSLN) and to compare this to
      analogous data of the recurrent laryngeal nerve (RLN) and vagus nerve (VN) during
      intraoperative neural monitoring (IONM) using both the standard monopolar
      stimulator probe and a novel bipolar stimulator probe. STUDY DESIGN: Prospective
      multiple tertiary care center study. METHOD: A prospective study of EBSLN, RLN
      and VN EMG data in 22 thyroid surgeries was performed. Subjects with preoperative
      vocal fold paralysis were excluded. Postoperative laryngoscopy was normal in all
      subjects. Normative EMG data were acquired using both a standard monopolar and a
      novel bipolar stimulator probe, as well as a novel endotracheal tube.
      Cricothyroid muscle (CTM) twitch response during EBSLN stimulation was analyzed.
      RESULTS: In 100% of cases, EBSLN was identified and quantifiable EMG response was
      observed. EMG amplitude did not change despite extensive nerve dissection and
      multiple nerve stimulations. EBSLN amplitude was similar for left and right sides
      for patients under age 50 and aged 50 or older, for both genders, and with
      monopolar and bipolar stimulators. CONCLUSIONS: Intraoperative neural monitoring
      may be used to safely assist in EBSLN identification during thyroid surgery in
      100% of patients. A novel endotracheal tube allows for quantifiable EBSLN EMG
      activity in 100% of cases. Monopolar and bipolar stimulator probes produce
      similar EMG data. LEVEL OF EVIDENCE: 4.

PMID- 24115216
TI  - A highly efficient palladium-catalyzed decarboxylative ortho-acylation of
      azobenzenes with alpha-oxocarboxylic acids: direct access to acylated azo
      compounds.
AB  - Avoiding additives: A highly efficient and mild Pd-catalyzed decarboxylative
      ortho-acylation of azobenzenes with alpha-oxocarboxylic acids was developed that
      provides an alternative route to acylated azo compounds. This decarboxylative
      acylation process was completed in the absence of any additives at ambient
      temperature, to afford the acylated azobenzenes in moderate to good yields. 

PMID- 24115217
TI  - Association of vascular invasion with increased mortality in patients with
      minimally invasive follicular thyroid carcinoma but not widely invasive
      follicular thyroid carcinoma.
AB  - BACKGROUND: The association of vascular invasion with tumor aggressiveness and
      poor prognosis in follicular thyroid carcinoma (FTC) remains controversial.
      METHODS: We reviewed medical records of 204 patients with histologically
      confirmed FTC. RESULTS: The disease-specific survival rates at 5 and 10 years
      were 94% and 85%, respectively. Using Cox proportional hazard model, the extent
      of invasiveness and the frequency of distant metastasis were found to be
      independent prognostic factors for survival in all patients with FTC. When we
      performed individual analyses stratified by the extent of invasiveness, vascular
      invasion was an independent predictor of disease-specific survival in minimally
      invasive FTC, but that did not independently affect survival in widely invasive
      FTC. CONCLUSION: This study suggests that vascular invasion is associated with
      aggressive features of FTC and independently influences outcomes in minimally
      invasive FTC. For patients aged <45 years with minimally invasive FTC without
      vascular invasion, thyroid lobectomy alone may be adequate.

PMID- 24115218
TI  - Inhibition of EGFR induces a c-MET-driven stem cell population in glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most lethal form of primary brain tumors,
      characterized by highly invasive and aggressive tumors that are resistant to all
      current therapeutic options. GBMs are highly heterogeneous in nature and contain
      a small but highly tumorigenic and self-renewing population of stem or initiating
      cells (glioblastoma stem cells or GSCs). GSCs have been shown to contribute to
      tumor propagation and resistance to current therapeutic modalities. Recent
      studies of human GBMs have elucidated the genetic alterations common in these
      tumors, but much remains unknown about specific signaling pathways that regulate
      GSCs. Here we identify a distinct fraction of cells in a genetically engineered
      mouse model of EGFR-driven GBM that respond to anti-EGFR therapy by inducing high
      levels of c-MET expression. The MET-positive cells displayed clonogenic potential
      and long-term self-renewal ability in vitro and are capable of differentiating
      into multiple lineages. The MET-positive GBM cells are resistant to radiation and
      highly tumorigenic in vivo. Activation of MET signaling led to an increase in
      expression of the stemness transcriptional regulators Oct4, Nanog, and Klf4.
      Pharmacological inhibition of MET activity in GSCs prevented the activation of
      Oct4, Nanog, and Klf4 and potently abrogated stemness. Finally, the MET
      expressing cells were preferentially localized in perivascular regions of mouse
      tumors consistent with their function as GSCs. Together, our findings indicate
      that EGFR inhibition in GBM induces MET activation in GSCs, which is a functional
      requisite for GSCs activity and thus represents a promising therapeutic target.

PMID- 24115219
TI  - Neurogenic differentiation capacity of subacromial bursal tissue-derived stem
      cells.
AB  - In this study, analysis and comprehensive comparison of neurogenic
      differentiation capacity of human bursal tissue-derived-stem cells (hBT-SCs) was
      aimed with human bone marrow derived mesenchymal stem cells (hBM-MSCs). hBT-SCs
      was isolated from subacromial bursa tissue (n = 3) by collagen type-II digestion.
      The expression of stem cell markers, differentiation capacity and telomerase
      activity were determined for both cell lines. The expression levels of neurogenic
      cell markers were compared consecutively. With respect to the surface marker
      profile, both cells display similar pluripotency phenotypes. Both cells
      successfully differentiated into osteo- and adipogenic cell lines. The immune
      staining of mesenchymal, stem cell and neurogenic markers gave positive reaction.
      The gene expression level for Tubb3, Nestin, Gfap, Map2, Nf-h, and Nf-l was
      higher in hBT-SCs than hBM-MSCs. The high level of neurotrophic factors, like
      Tenascin C, NGF, BDNF, VEGF, and CNTF might indicate their regeneration and
      maintenance capacity in damaged neural tissue. Besides they are alternative
      source for human mesenchymal stem cells, hBT-SCs assess the possibility to use in
      clinical studies.

PMID- 24115220
TI  - IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in
      patients with myelodysplastic syndromes and are stable during disease evolution.
AB  - Current information about clinical significance of IDH mutations in
      myelodysplastic syndromes (MDS), their association with other genetic alterations
      and the stability during disease progression is limited. In this study, IDH
      mutations were identified in 4.6% of 477 patients with MDS based on the FAB
      classification and in 2.2 % of 368 patients based on the 2008 WHO classification.
      IDH mutations were closely associated with older age, higher platelet counts, and
      mutations of DNMT3A (36.4% vs. 8.7%, P < 0.001), ASXL1 (47.6% vs. 22.0%, P =
      0.007), and SRSF2 (45.5% vs. 11.8%, P < 0.001). IDH2 mutation was a poor
      prognostic factor for overall survival in patients with lower-risk MDS, based on
      international prognosis scoring system (IPSS), FAB classification, WHO
      classification, or revised IPSS (all P ? 0.001), but not in higher-risk groups.
      Sequential studies in 151 patients demonstrated that all IDH-mutated patients
      retained the same mutation during disease evolution while none of the IDH-wild
      patients acquired a novel mutation during follow-ups. In conclusion, IDH mutation
      is a useful biomarker for risk stratification of patients with lower-risk MDS.
      IDH mutations are stable during the clinical course. The mutation, in association
      with other genetic alterations, may play a role in the development, but not
      progression of MDS.

PMID- 24115221
TI  - Evaluation of ERG responsive proteome in prostate cancer.
AB  - BACKGROUND: Gene fusion between TMPRSS2 promoter and the ERG proto-oncogene is a
      major genomic alteration found in over half of prostate cancers (CaP), which
      leads to aberrant androgen dependent ERG expression. Despite extensive analysis
      for the biological functions of ERG in CaP, there is no systematic evaluation of
      the ERG responsive proteome (ERP). ERP has the potential to define new biomarkers
      and therapeutic targets for prostate tumors stratified by ERG expression.
      METHODS: Global proteome analysis was performed by using ERG (+) and ERG (-) CaP
      cells isolated by ERG immunohistochemistry defined laser capture microdissection
      and by using TMPRSS2-ERG positive VCaP cells treated with ERG and control siRNA.
      RESULTS: We identified 1,196 and 2,190 unique proteins stratified by ERG status
      from prostate tumors and VCaP cells, respectively. Comparative analysis of these
      two proteomes identified 330 concordantly regulated proteins characterizing
      enrichment of pathways modulating cytoskeletal and actin reorganization, cell
      migration, protein biosynthesis, and proteasome and ER-associated protein
      degradation. ERPs unique for ERG (+) tumors reveal enrichment for cell growth and
      survival pathways while proteasome and redox function pathways were enriched in
      ERPs unique for ERG (-) tumors. Meta-analysis of ERPs against CaP gene expression
      data revealed that Myosin VI and Monoamine oxidase A were positively and
      negatively correlated to ERG expression, respectively. CONCLUSIONS: This study
      delineates the global proteome for prostate tumors stratified by ERG expression
      status. The ERP data confirm the functions of ERG in inhibiting cell
      differentiation and activating cell growth, and identify potentially novel
      biomarkers and therapeutic targets.

PMID- 24115223
TI  - Structure of active coagulation factor XIII triggered by calcium binding: basis
      for the design of next-generation anticoagulants.

PMID- 24115222
TI  - Perlecan-containing pericellular matrix regulates solute transport and
      mechanosensing within the osteocyte lacunar-canalicular system.
AB  - The pericellular matrix (PCM), a thin coating surrounding nearly all mammalian
      cells, plays a critical role in many cell-surface phenomena. In osteocytes, the
      PCM is believed to control both "outside-in" (mechanosensing) and "inside-out"
      (signaling molecule transport) processes. However, the osteocytic PCM is
      challenging to study in situ because it is thin (~100 nm) and enclosed in
      mineralized matrix. To this end, we recently developed a novel tracer velocimetry
      approach that combined fluorescence recovery after photobleaching (FRAP) imaging
      with hydrodynamic modeling to quantify the osteocytic PCM in young murine bone.
      In this study, we applied the technique to older mice expressing or deficient for
      perlecan/HSPG2, a large heparan-sulfate proteoglycan normally secreted in
      osteocytic PCM. The objectives were (1) to characterize transport within an
      altered PCM; (2) to test the sensitivity of our approach in detecting the PCM
      alterations; and (3) to dissect the roles of the PCM in osteocyte mechanosensing.
      We found that: (1) solute transport increases in the perlecan-deficient
      (hypomorphic [Hypo]) mice compared with control mice; (2) PCM fiber density
      decreases with aging and perlecan deficiency; (3) osteocytes in the Hypo bones
      are predicted to experience higher shear stress (+34%), but decreased fluid drag
      force (-35%) under 3-N peak tibial loading; and (4) when subjected to tibial
      loading in a preliminary in vivo experiment, the Hypo mice did not respond to the
      anabolic stimuli as the CTL mice did. These findings support the hypothesis that
      the PCM fibers act as osteocyte's sensing antennae, regulating load-induced
      cellular stimulations and thus bone's sensitivity and in vivo bone adaptation. If
      this hypothesis is further confirmed, osteocytic PCM could be new targets to
      develop osteoporosis treatments by modulating bone's intrinsic sensitivity to
      mechanical loading and be used to design patient-specific exercise regimens to
      promote bone formation.

PMID- 24115224
TI  - Anthropogenic nitrogen deposition in boreal forests has a minor impact on the
      global carbon cycle.
AB  - It is proposed that increases in anthropogenic reactive nitrogen (Nr ) deposition
      may cause temperate and boreal forests to sequester a globally significant
      quantity of carbon (C); however, long-term data from boreal forests describing
      how C sequestration responds to realistic levels of chronic Nr deposition are
      scarce. Using a long-term (14-year) stand-scale (0.1 ha) N addition experiment
      (three levels: 0, 12.5, and 50 kg N ha(-1)  yr(-1) ) in the boreal zone of
      northern Sweden, we evaluated how chronic N additions altered N uptake and
      biomass of understory communities, and whether changes in understory communities
      explained N uptake and C sequestration by trees. We hypothesized that understory
      communities (i.e. mosses and shrubs) serve as important sinks for low-level N
      additions, with the strength of these sinks weakening as chronic N addition rates
      increase, due to shifts in species composition. We further hypothesized that
      trees would exhibit nonlinear increases in N acquisition, and subsequent C
      sequestration as N addition rates increased, due to a weakening understory N
      sink. Our data showed that understory biomass was reduced by 50% in response to
      the high N addition treatment, mainly due to reduced moss biomass. A (15) N
      labeling experiment showed that feather mosses acquired the largest fraction of
      applied label, with this fraction decreasing as the chronic N addition level
      increased. Contrary to our hypothesis, the proportion of label taken up by trees
      was equal (ca. 8%) across all three N addition treatments. The relationship
      between N addition and C sequestration in all vegetation pools combined was
      linear, and had a slope of 16 kg C kg(-1)  N. While canopy retention of Nr
      deposition may cause C sequestration rates to be slightly different than this
      estimate, our data suggest that a minor quantity of annual anthropogenic CO2
      emissions are sequestered into boreal forests as a result of Nr deposition. 

PMID- 24115225
TI  - Novel inflammatory biomarkers of portal pressure in compensated cirrhosis
      patients.
AB  - The rationale for screening inflammatory serum biomarkers of the hepatic vein
      pressure gradient (HVPG) is based on the fact that portal hypertension is
      pathogenically related to liver injury and fibrosis, and that in turn these are
      associated with the activation of inflammatory pathways. This was a nested cohort
      study in the setting of a randomized, clinical trial to assess the development of
      gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had
      cirrhosis and portal hypertension but did not have GEV. A total of 90 patients
      who had baseline day-1 sera available were enrolled in the present study. The
      objective of this study was to determine whether inflammatory biomarkers in
      conjunction with clinical parameters could be used to develop a predictive
      paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1beta
      (P=0.0052); IL-1R-alpha (P=0.0085); Fas-R (P=0.0354), and serum VCAM-1 (P=0.0007)
      were highly significant. By using multivariate logistic regression analysis and
      selected parameters (transforming growth factor beta [TGFbeta]; heat shock
      protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG
      >= 12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and
      the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite
      test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg
      and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity
      and costs in these patients. Our diagnostic test was not efficient in predicting
      HVPG >= 12 mmHg. CONCLUSION: A blood test for HVPG could be performed in
      cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy.

PMID- 24115226
TI  - Novel technique for generating macrophage foam cells for in vitro reverse
      cholesterol transport studies.
AB  - Generation of foam cells, an essential step for reverse cholesterol transport
      studies, uses the technique of receptor-dependent macrophage loading with
      radiolabeled acetylated LDL. In this study, we used the ability of a biologically
      relevant detergent molecule, lysophosphatidylcholine (lyso-PtdCho), to form mixed
      micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam
      cells. Fluorescent or radiolabeled cholesterol/lyso-PtdCho mixed micelles were
      prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Results
      showed that such micelles were quite stable at 4 degrees C and retained the
      solubilized cholesterol during one month of storage. Macrophages incubated with
      cholesterol or CE (unlabeled, fluorescently labeled, or radiolabeled)/lyso-PtdCho
      mixed micelles accumulated CE as documented by microscopy, lipid staining,
      labeled oleate incorporation, and by TLC. Such foam cells unloaded cholesterol
      when incubated with HDL but not with oxidized HDL. We propose that stable
      cholesterol or CE/lyso-PtdCho micelles would offer advantages over existing
      methods. 

PMID- 24115228
TI  - Highly strained phenylene bicyclophanes.

PMID- 24115227
TI  - A model of in vitro UDP-glucuronosyltransferase inhibition by bile acids predicts
      possible metabolic disorders.
AB  - Increased levels of bile acids (BAs) due to the various hepatic diseases could
      interfere with the metabolism of xenobiotics, such as drugs, and endobiotics
      including steroid hormones. UDP-glucuronosyltransferases (UGTs) are involved in
      the conjugation and elimination of many xenobiotics and endogenous compounds. The
      present study sought to investigate the potential for inhibition of UGT enzymes
      by BAs. The results showed that taurolithocholic acid (TLCA) exhibited the
      strongest inhibition toward UGTs, followed by lithocholic acid. Structure-UGT
      inhibition relationships of BAs were examined and in vitro-in vivo extrapolation
      performed by using in vitro inhibition kinetic parameters (Ki) in combination
      with calculated in vivo levels of TLCA. Substitution of a hydrogen with a
      hydroxyl group in the R1, R3, R4, R5 sites of BAs significantly weakens their
      inhibition ability toward most UGTs. The in vivo inhibition by TLCA toward UGT
      forms was determined with following orders of potency: UGT1A4 > UGT2B7 > UGT1A3 >
      UGT1A1 ~ UGT1A7 ~ UGT1A10 ~ UGT2B15. In conclusion, these studies suggest that
      disrupted homeostasis of BAs, notably taurolithocholic acid, found in various
      diseases such as cholestasis, could lead to altered metabolism of xenobiotics and
      endobiotics through inhibition of UGT enzymes. 

PMID- 24115230
TI  - Total synthesis of (+)-asperolide C by iridium-catalyzed enantioselective polyene
      cyclization.

PMID- 24115229
TI  - Fluorescence spectroscopy of soluble E. coli SPase I Delta2-75 reveals
      conformational changes in response to ligand binding.
AB  - The bacterial Sec pathway is responsible for the translocation of secretory
      preproteins. During the later stages of transport, the membrane-embedded signal
      peptidase I (SPase I) cleaves the signal peptide from a preprotein. We used
      tryptophan fluorescence spectroscopy of a soluble, catalytically active E. coli
      SPase I Delta2-75 enzyme to study its dynamic conformational changes while in
      solution and when interacting with lipids and signal peptides. We generated four
      single Trp SPase I Delta2-75 mutants, W261, W284, W300, and W310. Based on
      fluorescence quenching experiments, W300 and W310 were found to be more solvent
      accessible than W261 and W284 in the absence of ligands. W300 and W310 inserted
      into lipids, consistent with their location at the enzyme's proposed membrane
      interface region, while the solvent accessibilities of W261, W284, and W300 were
      modified in the presence of signal peptide, suggesting propagation of structural
      changes beyond the active site in response to peptide binding. The signal peptide
      binding affinity for the enzyme was measured via FRET experiments and the Kd
      determined to be 4.4 MUM. The location of the peptide with respect to the enzyme
      was also established; this positioning is crucial for the peptide to gain access
      to the enzyme active site as it emerges from the translocon into the membrane
      bilayer. These studies reveal enzymatic structural changes required for
      preprotein proteolysis as it interacts with its two key partners, the signal
      peptide and membrane phospholipids.

PMID- 24115231
TI  - Successful closure of residual leak following LARIAT procedure in a patient with
      high risk of stroke and hemorrhage.
AB  - Percutaneous left atrial appendage suture ligation with the LARIAT(r) device
      (Sentre HEART, Redwood City, CA) was successfully performed on an 84-year-old
      woman with non-valvular atrial fibrillation who developed intracranial hemorrhage
      on warfarin. However, a large gap developed at follow-up precluding warfarin
      cessation. To the best of our knowledge, this case report represents the first
      description of the use of a Gore(r) Helex(r) Septal Occluder (W. L. Gore and
      Associates, Newark, Delaware) as a novel approach to close a gap following
      percutaneous LAA suture ligation.

PMID- 24115232
TI  - De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early
      onset epileptic encephalopathy.
AB  - Early-onset epileptic encephalopathies (EOEE) are severe neurological disorders
      characterized by frequent seizures accompanied by developmental regression or
      retardation. Whole-exome sequencing of 12 patients together with five pairs of
      parents and subsequent Sanger sequencing in additional 328 EOEE patients
      identified two de novo frameshift and one missense mutations in SLC35A2 at
      Xp11.23, respectively. The three patients are all females. X-inactivation
      analysis of blood leukocyte DNA and mRNA analysis using lymphoblastoid cells
      derived from two patients with a frameshift mutation indicated that only the wild
      type SLC35A2 allele was expressed in these cell types, at least in part likely as
      a consequence of skewed X-inactivation. SLC35A2 encodes a UDP-galactose
      transporter (UGT), which selectively supplies UDP-galactose from the cytosol to
      the Golgi lumen. Transient expression experiments revealed that the missense
      mutant protein was correctly localized in the Golgi apparatus. In contrast, the
      two frameshift mutant proteins were not properly expressed, suggesting that their
      function is severely impaired. Defects in the UGT can cause congenital disorders
      of glycosylation. Of note, no abnormalities of glycosylation were observed in
      three serum glycoproteins, which is consistent with favorably skewed X
      inactivation. We hypothesize that a substantial number of neurons might express
      the mutant SLC35A2 allele and suffer from defective galactosylation, resulting in
      EOEE. 

PMID- 24115233
TI  - On the regio- and stereospecificity of arachidonic acid peroxidation catalyzed by
      mammalian 15-lypoxygenases: a combined molecular dynamics and QM/MM study.
AB  - 15-Lipoxygenases (15-LOs) catalyse the peroxidation reaction of arachidonic acid
      (AA) in mammals with remarkable regio- and stereospecificity. This positional
      specific peroxidation is of paramount importance because it determines the nature
      and biological functions of the final metabolites generated by each LO as a
      result of the oxidative metabolism of AA. Although several hypotheses have been
      formulated concerning the regio- and stereospecificity of LOs, the molecular
      basis of such behaviour is still unclear. Herein, we combined quantum
      mechanics/molecular mechanics calculations with molecular dynamics simulations of
      the complete rabbit 15-LO/AA solvated model to examine the most accepted
      hypotheses for the regio- and stereospecificity of LOs. We have found that the
      clue to explain this specificity is the oxygen-targeting hypothesis through
      steric shielding of specific residues (mainly Leu597, Gln548 and Phe175, as well
      as the AA tail itself). Our deductions are based primarily on the analysis of the
      energy barrier heights from the oxygen addition reaction profiles. 

PMID- 24115234
TI  - Transcriptome profiling analysis of the mechanisms underlying the BDNF Val66Met
      polymorphism induced dysfunctions of the central nervous system.
AB  - Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects postnatal
      behaviors and is associated with a variety of neuropsychiatric disorders.
      However, the mechanisms underlying the BDNF(Met) variant induced dysfunctions of
      the central nervous system remain obscure. In order to identify the candidate
      genes and pathways responsible for the dysfunctions associated with this BDNF
      variation, we analyzed the expression of genes in the hippocampus, prefrontal
      cortex, and amygdala of the BDNF(Met) variant mice in comparison with the wild
      type mice using Illumina bead microarray. Transcriptome profiling analysis
      revealed region-distinctive and gene-dose dependent changes of gene expression
      associated with the BDNF(Met) variant. BDNF(Met) variant mice exhibited altered
      expression of genes associated with translational machinery, neuronal plasticity
      and mitochondrial function based on the gene ontology (GO) annotation. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the
      chemokine, cell adhesion, ubiquitin-proteosome and wnt signaling pathways were
      altered in the BDNF(Met) variant mice brain. Finally, the CX3CL1/CX3CR1 signaling
      was identified to be impaired in the hippocampus and microinjection of CX3CL1
      into the hippocampus could rescue the hippocampal dependent memory deficits in
      BDNF(Met/Met) mice, indicating that CX3CL1 may be an effective treatment option
      for memory disorders in humans with this genetic BDNF variation. These findings
      will help us further understanding the molecular mechanisms involved in the
      BDNF(Met) associated behavior and neuroanatomy alternations.

PMID- 24115235
TI  - Probing DNA mismatched and bulged structures by using 19F NMR spectroscopy and
      oligodeoxynucleotides with an 19F-labeled nucleobase.
AB  - In this study, DNA local structures with bulged bases and mismatched base pairs
      as well as ordinary full-matched base pairs by using (19)F NMR spectroscopy with
      (19)F-labeled oligodeoxynucleotides (ODNs) were monitored. The chemical shift
      change in the (19) F NMR spectra allowed discrimination of the DNA structures.
      Two types of ODNs possessing the bis(trifluoromethyl)benzene unit (F-unit) at
      specified uridines were prepared and hybridized with their complementary or
      noncomplementary strands to form matched, mismatched, or bulged duplexes. By
      using ODN F1, in which an F-unit was connected directly to a propargyl amine
      substituted uridine, three local structures, that is, full-matched, G-U mismatch,
      and A-bulge could be analyzed, whereas other structures could not be
      discriminated. A molecular modeling study revealed that the F-unit in ODN F1
      interacted little with the nucleobases and sugar backbone of the opposite strand
      because the linker length between the F-unit and the uridine base was too short.
      Therefore, the capacity of ODN F1 to discriminate the DNA local structures was
      limited. Thus, ODN F2 was designed to improve this system; aminobenzoic acid was
      inserted between the F-unit and uridine base so the F-unit could interact more
      closely with the opposite strand. Eventually, the G-bulge and T-U mismatch and
      the three aforementioned local structures could be discriminated by using ODN F2.
      In addition, the dissociation processes of these duplexes could be monitored
      concurrently by (19)F NMR spectroscopy.

PMID- 24115236
TI  - Design and preparation of single-chain nanocarriers mimicking disordered proteins
      for combined delivery of dermal bioactive cargos.
AB  - Inspired by the multifunctionality of vitamin D-binding protein and the multiple
      transient-binding behavior of some intrinsically disordered proteins (IDPs), a
      polymeric platform is designed, prepared, and characterized for combined delivery
      of dermal protective and anticancer bioactive cargos on the basis of artificial
      single-chain nano-objects mimicking IDPs. For the first time ever, simultaneous
      delivery of folic acid or vitamin B9 , and hinokitiol, a relevant natural
      bioactive compound that exhibits anticancer activity against human malignant
      melanoma cells, from these multidirectionally self-assembled unimolecular
      nanocarriers is illustrated. 

PMID- 24115237
TI  - Dynamic intraoperative MRI in transsphenoidal resection of pituitary
      macroadenomas: a quantitative analysis.
AB  - PURPOSE: To compare intraoperative dynamic contrast-enhanced (dCE) sequences with
      conventional CE (cCE) in the evaluation of the surgical bed after transsphenoidal
      removal of pituitary macroadenomas. MATERIALS AND METHODS: Twenty-one patients
      with macroadenoma were selected. They all underwent intraoperative magnetic
      resonance imaging (iMRI) (1.5T) acquisitions during transsphenoidal resection of
      the tumor. For each patient, dCE and cCE images were acquired in the operating
      room after tumor removal. The mean values of surgical cavities volumes were
      measured and statistically compared through Student's t-test analysis. Informed
      consent to iMRI was obtained from the patients as a part of the surgical
      procedure. Institutional Review Board (IRB) approval was obtained. RESULTS: No
      patient showed recurrence within at least 1 year of follow-up. Two patients
      showed residual tumor in the iMRI. Intraoperative analysis of the remaining 19
      demonstrated that the mean value of the surgical cavities was significantly
      bigger in dCE than in cCE images (2955 mm(3) vs. 1963 mm(3) , respectively, P =
      0.022). CONCLUSION: This study demonstrated underestimation of surgical cavity by
      conventional iMRI, simulating residual tumor and potentially leading to
      unnecessary surgical revision.

PMID- 24115238
TI  - Comparison of transfer sites for flexor digitorum longus in a cadaveric adult
      acquired flatfoot model.
AB  - Posterior tibialis tendon (PTT) dysfunction (PTTD) is associated with adult
      acquired flatfoot deformity. PTTD is commonly treated with a flexor digitorum
      longus (FDL) tendon transfer (FDLTT) to the navicular (NAV), medial cuneiform
      (CUN), or distal residuum of the degraded PTT (rPTT). We assessed the kinetic and
      kinematic outcomes of these three attachment sites using cadaveric gait
      simulation. Three transfer locations (NAV, CUN, rPTT) were tested on seven
      prepared flatfoot models using a robotic gait simulator (RGS). The FDLTT
      procedures were simulated by pulling on the PTT with biomechanically realistic
      FDL forces (rPTT) or by pulling on the transected FDL tendon after fixation to
      the navicular or medial cuneiform (NAV and CUN, respectively). Plantar pressure
      and foot bone motion were quantified. Peak plantar pressure significantly
      decreased from the flatfoot condition at the first metatarsal (NAV) and hallux
      (CUN). No difference was found in the medial-lateral center of pressure.
      Kinematic findings showed minimal differences between flatfoot and FDLTT
      specimens. The three locations demonstrated only minimal differences from the
      flatfoot condition, with the NAV and CUN procedures resulting in decreased medial
      pressures. Functionally, all three surgical procedures performed similarly.

PMID- 24115239
TI  - The impact of municipal wastewater effluent on field-deployed freshwater mussels
      in the Grand River (Ontario, Canada).
AB  - To examine effects of municipal wastewater effluent (MWWE) on sentinel organisms,
      the authors deployed caged freshwater mussels (Lasmigona costata) in the Grand
      River (ON, Canada) upstream and downstream of an MWWE outfall. Passive sampling
      devices were deployed alongside caged mussels to confirm exposure. Biomarkers of
      xenobiotic biotransformation, oxidative stress, estrogenicity, and
      immunomodulation were investigated. Elevated concentrations of selected
      pharmaceutical and personal care products (PPCPs) and a natural estrogen
      (estrone) were found at the downstream sites. Mussels caged downstream of the
      effluent for 2 wk showed minimal evidence of exposure, while those deployed for 4
      wk exhibited significantly higher levels of lipid peroxidation (LPO) and
      glutathione S-transferase (GST) activity, demonstrating that MWWE-exposed mussels
      exhibit increased activity in xenobiotic conjugation and oxidative stress. With
      respect to immune responses, a significant increase in plasma lysozyme activity
      and hemocyte viability was observed in MWWE-exposed mussels. Vitellogenin (vtg)
      like protein in male mussels showed a trend toward induction after 4 wk of
      deployment at the first downstream site, but mean levels were not significantly
      different. Discriminant function analysis indicated that mussels deployed for 4
      wk upstream and downstream of the MWWE discharge could be discriminated on the
      basis of LPO, GST, plasma lysozyme, and vtg responses. The physiological stress
      observed in caged mussels indicates that wild mussels chronically exposed to MWWE
      in this ecosystem would also be negatively impacted.

PMID- 24115240
TI  - TP53 single nucleotide polymorphism rs1042522 in salivary gland neoplasms.
AB  - BACKGROUND: The TP53 single nucleotide polymorphism (SNP) rs1042522 encodes
      arginine (Arg) or proline (Pro). The Arg variant is more effective at inducing
      apoptosis than the Pro. METHODS: We assessed this SNP through direct sequencing
      of benign and malignant salivary neoplasms of Brazilian patients and compared the
      results with healthy controls' data. BAX, BCL-2, and CASPASE-3 mRNA levels were
      assessed by quantitative polymerase chain reaction (qPCR) in a set of salivary
      tumors, and the results were correlated with the tumor genotype. RESULTS: We
      found a higher frequency of the Arg/Arg genotype in the malignant group. However,
      the SNP did not influence the age of onset in either benign or malignant tumors.
      The SNP was not associated with the transcription levels of
      apoptotic/antiapoptotic genes. CONCLUSION: Malignant salivary neoplasms showed a
      higher frequency of the allele encoding Arg and a higher frequency of the Arg/Arg
      genotype. However, the different genotypes did not impact the transcription of
      genes involved in apoptosis.

PMID- 24115241
TI  - CCAAT/enhancer-binding protein beta expressed by bone marrow mesenchymal stromal
      cells regulates early B-cell lymphopoiesis.
AB  - The transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta)
      regulates the differentiation of a variety of cell types. Here, the role of
      C/EBPbeta expressed by bone marrow mesenchymal stromal cells (BMMSCs) in B-cell
      lymphopoiesis was examined. The size of the precursor B-cell population in bone
      marrow was reduced in C/EBPbeta-knockout (KO) mice. When bone marrow cells from
      C/EBPbeta-KO mice were transplanted into lethally irradiated wild-type (WT) mice,
      which provide a normal bone marrow microenvironment, the size of the precursor B
      cell population was restored to a level equivalent to that generated by WT bone
      marrow cells. In coculture experiments, BMMSCs from C/EBPbeta-KO mice did not
      support the differentiation of WT c-Kit(+) Sca-1(+) Lineage(-) hematopoietic stem
      cells (KSL cells) into precursor B cells, whereas BMMSCs from WT mice did. The
      impaired differentiation of KSL cells correlated with the reduced production of
      CXCL12/stromal cell-derived factor-1 by the cocultured C/EBPbeta-deficient
      BMMSCs. The ability of C/EBPbeta-deficient BMMSCs to undergo osteogenic and
      adipogenic differentiation was also defective. The survival of leukemic precursor
      B cells was poorer when they were cocultured with C/EBPbeta-deficient BMMSCs than
      when they were cocultured with WT BMMSCs. These results indicate that C/EBPbeta
      expressed by BMMSCs plays a crucial role in early B-cell lymphopoiesis.

PMID- 24115242
TI  - Replicated throughfall exclusion experiment in an Indonesian perhumid rainforest:
      wood production, litter fall and fine root growth under simulated drought.
AB  - Climate change scenarios predict increases in the frequency and duration of ENSO
      related droughts for parts of South-East Asia until the end of this century
      exposing the remaining rainforests to increasing drought risk. A pan-tropical
      review of recorded drought-related tree mortalities in more than 100 monitoring
      plots before, during and after drought events suggested a higher drought
      vulnerability of trees in South-East Asian than in Amazonian forests. Here, we
      present the results of a replicated (n = 3 plots) throughfall exclusion
      experiment in a perhumid tropical rainforest in Sulawesi, Indonesia. In this
      first large-scale roof experiment outside semihumid eastern Amazonia, 60% of the
      throughfall was displaced during the first 8 months and 80% during the subsequent
      17 months, exposing the forest to severe soil desiccation for about 17 months. In
      the experiment's second year, wood production decreased on average by 40% with
      largely different responses of the tree families (ranging from -100 to +100%
      change). Most sensitive were trees with high radial growth rates under moist
      conditions. In contrast, tree height was only a secondary factor and wood
      specific gravity had no influence on growth sensitivity. Fine root biomass was
      reduced by 35% after 25 months of soil desiccation while fine root necromass
      increased by 250% indicating elevated fine root mortality. Cumulative aboveground
      litter production was not significantly reduced in this period. The trees from
      this Indonesian perhumid rainforest revealed similar responses of wood and litter
      production and root dynamics as those in two semihumid Amazonian forests
      subjected to experimental drought. We conclude that trees from paleo- or
      neotropical forests growing in semihumid or perhumid climates may not differ
      systematically in their growth sensitivity and vitality under sublethal drought
      stress. Drought vulnerability may depend more on stem cambial activity in moist
      periods than on tree height or wood specific gravity. 

PMID- 24115243
TI  - Transmission of dengue virus from a donor to a recipient after living donor liver
      transplantation.

PMID- 24115244
TI  - 25th anniversary article: CVD polymers: a new paradigm for surface modification
      and device fabrication.
AB  - Well-adhered, conformal, thin (<100 nm) coatings can easily be obtained by
      chemical vapor deposition (CVD) for a variety of technological applications. Room
      temperature modification with functional polymers can be achieved on virtually
      any substrate: organic, inorganic, rigid, flexible, planar, three-dimensional,
      dense, or porous. In CVD polymerization, the monomer(s) are delivered to the
      surface through the vapor phase and then undergo simultaneous polymerization and
      thin film formation. By eliminating the need to dissolve macromolecules, CVD
      enables insoluble polymers to be coated and prevents solvent damage to the
      substrate. CVD film growth proceeds from the substrate up, allowing for
      interfacial engineering, real-time monitoring, and thickness control. Initiated
      CVD shows successful results in terms of rationally designed micro- and
      nanoengineered materials to control molecular interactions at material surfaces.
      The success of oxidative-CVD is mainly demonstrated for the deposition of organic
      conducting and semiconducting polymers. 

PMID- 24115247
TI  - Hip fracture aggravates systemic inflammation and lung injury in aged chronic
      cigarette smoke exposed rats.
AB  - The aim of this investigation was to examine the influence of hip fracture on
      systemic inflammation and lung injury in aged chronic cigarette smoke exposed
      rats. Male Sprague Dawley (SD) aged rats (22-25 months old, 460-570 g) were used.
      Animals were subjected to either chronic cigarette smoke (CS) or air exposure for
      12 weeks. These animals then underwent a sham procedure or hip fracture. Endpoint
      was 24 h. Systemic inflammation was assessed by TNF-alpha, IL-6, and IL-10
      levels. Pulmonary function, inflammatory cell counts and protein concentrations
      in BAL, pulmonary pathological changes and scores were obtained to assess lung
      injury. And TLR4 mRNA expression in lung tissue was determined. The indices
      mentioned above were unchanged in air-exposed rats after hip fracture. However,
      CS-exposed animals were found to have increased serum levels of TNF-alpha, IL-6,
      and IL-10, impaired pulmonary function, increased inflammatory cell counts and
      protein concentrations in BAL, and intensified pathologic changes and scores. In
      addition, lung tissue harvested following CS-exposure demonstrated increased TLR4
      mRNA expression. Our results indicate that systemic inflammation and lung injury
      in aged CS-exposed animals were further aggravated by hip fracture. The
      overexpression of TLR4 mRNA induced by CS exposure may, at least in part, involve
      in this process.

PMID- 24115248
TI  - Lysophosphatidic acid (LPA) and its receptor, LPA1 , influence embryonic schwann
      cell migration, myelination, and cell-to-axon segregation.
AB  - Schwann cell (SC) migration is an important step preceding myelination and
      remyelination in the peripheral nervous system, and can be promoted by peptide
      factors like neuregulins. Here we present evidence that a lipid factor,
      lysophosphatidic acid (LPA), influences both SC migration and peripheral
      myelination through its cognate G protein-coupled receptor (GPCR) known as LPA1 .
      Ultrastructural analyses of peripheral nerves in mouse null-mutants for LPA1
      showed delayed SC-to-axon segregation, polyaxonal myelination by single SCs, and
      thinner myelin sheaths. In primary cultures, LPA promoted SC migration through
      LPA1 , while analysis of conditioned media from purified dorsal root ganglia
      neurons using HPLC/MS supported the production of LPA by these neurons. The
      heterotrimeric G-alpha protein, Galphai , and the small GTPase, Rac1, were
      identified as important downstream signaling components of LPA1 . These results
      identify receptor mediated LPA signaling between neurons and SCs that promote SC
      migration and contribute to the normal development of peripheral nerves through
      effects on SC-axon segregation and myelination.

PMID- 24115249
TI  - Matrix metalloprotease activity shapes the magnitude of EPSPs and spike
      plasticity within the hippocampal CA3 network.
AB  - Matrix metalloproteases (MMP) play a pivotal role in long-term synaptic
      plasticity, learning, and memory. The roles of different MMP subtypes are
      emerging, but the proteolytic activity of certain MMPs was shown to support these
      processes through the structural and functional modification of hippocampal
      Schaeffer collateral and mossy fiber (MF) synapses. However, certain patterns of
      synaptic activity are additionally associated with non-synaptic changes, such as
      the scaling of neuronal excitability. However, the extent to which MMPs affect
      this process remains unknown. We determined whether MMP activity interferes with
      excitatory post-synaptic potential EPSP-to-spike (E-S) coupling under conditions
      of varying synaptic activity. We evoked short- and long-term synaptic plasticity
      at associational/commissural (A/C) synapses of CA3 pyramidal neurons and
      simultaneously recorded population spikes (PSs) and EPSPs in acute rat (P30-60)
      brain slices in the presence of various MMP inhibitors. We found that MMP
      inhibition significantly reduced E-S coupling and shortened the PS latency
      associated with 4* 100 Hz stimulation or paired burst activity of MF-CA3 and A/C
      synapses. Moreover, MMP inhibition interfered with the scaling of amplitude of
      measured signals during high-frequency trains, thus affecting the induction of
      long-term potentiation (LTP). The inhibition of L-type voltage-gated calcium
      channels with 20 uM nifedipine or GABA-A receptors with 1-30 uM picrotoxin did
      not occlude the effects of MMP inhibitors. However, MMP inhibition significantly
      reduced the LTP of NMDA receptor-mediated EPSPs. Finally, the analysis of LTP
      saturation with multiple single (1* 100 Hz) or packed (4* 100 Hz) trains
      indicated that MMPs support E-S coupling evoked by selected synaptic activity
      patterns and set the ceiling for tetanically evoked E-S LTP. In conclusion, the
      activity of MMPs, particularly MMP-3, regulated the magnitude of EPSPs and spike
      plasticity in the CA3 network and may affect information processing. Our data
      provide a novel link between MMP activity and neural excitability. Therefore, by
      limiting the number of firing neurons, MMP may functionally act beyond the
      synapse.

PMID- 24115250
TI  - Assessment of bone microarchitecture in postmenopausal women on long-term
      bisphosphonate therapy with atypical fractures of the femur.
AB  - Reports of atypical femoral fractures (AFFs) in patients receiving long- term
      bisphosphonate therapy have raised concerns regarding the genesis of this rare
      event. Using high-resolution peripheral quantitative computed tomography (HR
      pQCT), we conducted a study to evaluate bone microarchitecture in patients who
      had suffered an AFF during long-term bisphosphonate treatment. The aim of our
      study was to evaluate if bone microarchitecture assessment could help explain the
      pathophysiology of these fractures. We compared bone volumetric density and
      microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20
      patients with AFFs with 35 postmenopausal women who had also received long-term
      bisphosphonate treatment but had not experienced AFFs, and with 54 treatment
      naive postmenopausal women. Control groups were similar in age, body mass index
      (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was
      71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was 
      2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None
      of the patients had other conditions associated with AFFs such as rheumatoid
      arthritis, diabetes or glucocorticoid use. There were no statistically
      significant differences in any of the parameters measured by HR-pQCT between
      postmenopausal women with or without treatment history and with or without
      history of atypical fractures. We could not find any distinctive
      microarchitecture features in the peripheral skeleton of women who had suffered
      an atypical fracture of the femur while receiving bisphosphonate treatment. This
      suggests that risk of developing an atypical fracture is not related to bone
      microarchitecture deterioration. Our results indicate that there may be other
      individual factors predisposing to atypical fractures in patients treated with
      bisphosphonates, and that those are independent of bone microarchitecture. In the
      future, identification of those factors could help prevent and understand the
      complex physiopathology of these rare events.

PMID- 24115251
TI  - Biomimetic total synthesis of (+/-)-merochlorin A.

PMID- 24115252
TI  - Conversations in mid-career: three academic researchers reflect on the field.

PMID- 24115255
TI  - Introduction to a special edition of Annals: Therapeutic prospects.

PMID- 24115256
TI  - Blockbusters for cheap? The difficulties surrounding generic biologics.

PMID- 24115258
TI  - A theoretical DFT-based and experimental study of the transmetalation step in
      Au/Pd-mediated cross-coupling reactions.
AB  - In this work a combined theoretical and experimental investigation of the cross
      coupling reaction involving two metallic reaction centers, namely gold and
      palladium, is described. One metal center (Au) hereby is rather inert towards
      change in its oxidation state, whereas Pd undergoes oxidative insertion and
      reductive elimination steps. Detailed mechanistic and energetic studies of each
      individual step, with the focus on the key transmetalation step are presented and
      compared for different substrates and ligands on the catalytic Pd center.
      Different aryl halides (Cl, Br, I) and aryl triflates were investigated. Hereby
      the nature of the counteranion X turned out to be crucial. In the case of X=Cl
      and L=PMe3 the oxidative addition is rate-determining, whereas in the case of X=I
      the transmetalation step becomes rate-determining in the Au/Pd-cross-coupling
      mechanism. A variety of Au-Pd transmetalation reaction scenarios are discussed in
      detail, favoring a transition state with short intermetallic Au-Pd contacts.
      Furthermore, without a halide counteranion the transmetalation from gold(I) to
      palladium(II) is highly endothermic, which confirms our experimental findings
      that the coupling does not occur with aryl triflates and similar weakly
      coordinating counteranions--a conclusion that is essential in designing new Au-Pd
      catalytic cycles. In combination with experimental work, this corrects a previous
      report in the literature claiming a successful coupling potentially catalytic in
      both metals with weakly coordinating counteranions.

PMID- 24115259
TI  - Low-temperature solution processing of mesoporous metal-sulfide semiconductors as
      light-harvesting photoanodes.

PMID- 24115260
TI  - Severity of X-linked dyskeratosis congenita (DKCX) cellular defects is not
      directly related to dyskerin (DKC1) activity in ribosomal RNA biogenesis or mRNA
      translation.
AB  - Dyskerin (encoded by the DKC1 locus) is the pseudouridine synthase responsible
      for the modification of noncoding RNA. Dyskerin is also an obligate member of the
      telomerase enzyme, and participates in the biogenesis of telomerase. Genetic
      lesions at the DKC1 locus are associated with X-linked dyskeratosis congenita (X
      DC) and the Hoyeraal-Hreidarsson Syndrome (HHS). Both syndromes have been linked
      to deficient telomere maintenance, but little is known about the RNA modification
      activities of dyskerin in X-DC and HHS cells. To evaluate whether X-DC-associated
      dyskerin mutations affect the modification or function of ribosomal RNA, we
      studied five telomerase-rescued X-DC cells (X-DC(T) ). Our data revealed a small
      reproducible loss of pseudouridines in mature rRNA in two X-DC variants. However,
      we found no difference in protein synthesis between telomerized wild-type (WT(T)
      ) and X-DC(T) cells, with an internal ribosomal entry site translation assay, or
      by measuring total protein synthesis in live cells. X-DC(T) cells and WT(T) cells
      also exhibited similar tolerances to ionizing radiation and endoplasmic reticulum
      stress. Despite the loss in rRNA pseudouridine modification, functional
      perturbations from these changes are secondary to the telomere maintenance
      defects of X-DC. Our data show that telomere dysfunction is the primary and
      unifying etiology of X-DC. 

PMID- 24115261
TI  - Role of retinol binding protein 4 in hepatic steatosis.

PMID- 24115262
TI  - Electrophoresis-chemiluminescence detection of phenols catalyzed by hemin.
AB  - Based on the catalytic activity of hemin, an efficient biocatalyst, an indirect
      capillary electrophoresis-chemiluminescence (CE-CL) detection method for phenols
      using a hemin-luminol-hydrogen peroxide system was developed. Through a series of
      static injection experiments, hemin was found to perform best in a neutral
      solution rather than an acidic or alkaline medium. Although halide ions such as
      Br(-) and F(-) could further enhance the CL signal catalyzed by hemin, it is
      difficult to apply these conditions to this CE-CL detection system because of the
      self-polymerization of hemin, as it hinders the CE process. The addition of
      concentrated ammonium hydroxide to an aqueous/dimethyl sulfoxide solution of
      hemin-luminol afforded a stable CE-CL baseline. The indirect CE-CL detection of
      five phenols using this method gave the following limits of detections: 4.8 * 10(
      8) mol/L (o-sec-butylphenol), 4.9 * 10(-8) mol/L (o-cresol), 5.4 * 10(-8) mol/L
      (m-cresol), 5.3 * 10(-8) mol/L (2,4-dichlorophenol) and 7.1 * 10(-8) mol/L
      (phenol).

PMID- 24115263
TI  - Highly efficient etherification of silanes by using a gold nanoparticle catalyst:
      remarkable effect of O(2).
AB  - O2 is acting! A nanosized hydroxylapatite-supported Au nanoparticle (NP) catalyst
      exhibited high activity under aerobic conditions, and various silyl ethers could
      be obtained from diverse combinations of silanes with alcohols. Moreover, O2 was
      found to act not as a stoichiometric oxidizing reagent, but as a non-consumed
      promoter, significantly boosting the catalytic activity of AuNPs. 

PMID- 24115264
TI  - Investigating alternatives to the fish early-life stage test: a strategy for
      discovering and annotating adverse outcome pathways for early fish development.
AB  - The fish early-life stage (FELS) test (Organisation for Economic Co-operation and
      Development [OECD] test guideline 210) is the primary test used internationally
      to estimate chronic fish toxicity in support of ecological risk assessments and
      chemical management programs. As part of an ongoing effort to develop efficient
      and cost-effective alternatives to the FELS test, there is a need to identify and
      describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To
      support this endeavor, the authors outline and illustrate an overall strategy for
      the discovery and annotation of FELS AOPs. Key events represented by major
      developmental landmarks were organized into a preliminary conceptual model of
      fish development. Using swim bladder inflation as an example, a weight-of
      evidence-based approach was used to support linkage of key molecular initiating
      events to adverse phenotypic outcomes and reduced young-of-year survival. Based
      on an iterative approach, the feasibility of using key events as the foundation
      for expanding a network of plausible linkages and AOP knowledge was explored and,
      in the process, important knowledge gaps were identified. Given the scope and
      scale of the task, prioritization of AOP development was recommended and key
      research objectives were defined relative to factors such as current animal-use
      restrictions in the European Union and increased demands for fish toxicity data
      in chemical management programs globally. The example and strategy described are
      intended to guide collective efforts to define FELS-related AOPs and develop
      resource-efficient predictive assays that address the toxicological domain of the
      OECD 210 test.

PMID- 24115265
TI  - Global reaction pathways in the photodissociation of I3 (-) ions in solution at
      267 and 400 nm studied by picosecond X-ray liquidography.
AB  - The mechanism of a photochemical reaction involves the formation and dissociation
      of various short-lived species on ultrafast timescales and therefore its
      characterization requires detailed structural information on the transient
      species. By making use of a structurally sensitive X-ray probe, time-resolved X
      ray liquidography (TRXL) can directly elucidate the structures of reacting
      molecules in the solution phase and thus determine the comprehensive reaction
      mechanism with high accuracy. In this work, by performing TRXL measurements at
      two different wavelengths (400 and 267 nm), the reaction mechanism of I3 (-)
      photolysis, which changes subtly depending on the excitation wavelength, is
      elucidated. Upon 400 nm photoexcitation, the I3 (-) ion dissociates into I2 (-)
      and I. By contrast, upon 267 nm photoexcitation, the I3 (-) ion undergoes both
      two-body dissociation (I2 (-) +I) and three-body dissociation (I(-) +2I) with 7:3
      molar ratio. At both excitation wavelengths, all the transient species ultimately
      disappear in 80 ns by recombining to form the I3 (-) ion nongeminately. In
      addition to the reaction dynamics of solute species, the results reveal the
      transient structure of the solute/solvent cage and the changes in solvent density
      and temperature as a function of time. 

PMID- 24115266
TI  - Is climate warming more consequential towards poles? The phenology of Lepidoptera
      in Finland.
AB  - The magnitude and direction of phenological shifts from climate warming could be
      predictably variable across the planet depending upon the nature of physiological
      controls on phenology, the thermal sensitivity of the developmental processes and
      global patterns in the climate warming. We tested this with respect to the flight
      phenology of adult nocturnal moths (3.33 million captures of 334 species) that
      were sampled at sites in southern and northern Finland during 1993-2012 (with
      years 2005-2012 treated as an independent model validation data set). We compared
      eight competing models of physiological controls on flight phenology to each
      species and found strong support for thermal controls of phenology in 66% of the
      species generations. Among species with strong thermal control of phenology in
      both the south and north, the average development rate was higher in northern vs.
      southern populations at 10  degrees C, but about the same at 15 and 20  degrees
      C. With a 3  degrees C increase in temperature (approximating A2 scenario of IPPC
      for 2090-2099 relative to 1980-1999) these species were predicted to advance
      their phenology on average by 17 (SE +/- 0.3) days in the south vs. 13 (+/-0.4)
      days in the north. The higher development rates at low temperatures of poleward
      populations makes them less sensitive to climate warming, which opposes the
      tendency for stronger phenological advances in the north from greater increases
      in temperature. 

PMID- 24115267
TI  - Spontaneous reactivation of clusters of X-linked genes is associated with the
      plasticity of X-inactivation in mouse trophoblast stem cells.
AB  - Random epigenetic silencing of the X-chromosome in somatic tissues of female
      mammals equalizes the dosage of X-linked genes between the sexes. Unlike this
      form of X-inactivation that is essentially irreversible, the imprinted
      inactivation of the paternal X, which characterizes mouse extra-embryonic
      tissues, appears highly unstable in the trophoblast giant cells of the placenta.
      Here, we wished to determine whether such instability is already present in
      placental progenitor cells prior to differentiation toward lineage-specific cell
      types. To this end, we analyzed the behavior of a GFP transgene on the paternal X
      both in vivo and in trophoblast stem (TS) cells derived from the trophectoderm of
      XX(GFP) blastocysts. Using single-cell studies, we show that not only the GFP
      transgene but also a large number of endogenous genes on the paternal X are
      subject to orchestrated cycles of reactivation/de novo inactivation in placental
      progenitor cells. This reversal of silencing is associated with local losses of
      histone H3 lysine 27 trimethylation extending over several adjacent genes and
      with the topological relocation of the hypomethylated loci outside of the nuclear
      compartment of the inactive X. The "reactivated" state is maintained through
      several cell divisions. Our study suggests that this type of "metastable
      epigenetic" states may underlie the plasticity of TS cells and predispose
      specific genes to relaxed regulation in specific subtypes of placental cells.

PMID- 24115268
TI  - MALDI MS profiling of post-DRE urine samples highlights the potential of beta
      microseminoprotein as a marker for prostatic diseases.
AB  - BACKGROUND: To use spectra acquired by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) from pre- and post-digital
      rectal examination (DRE) urine samples to search for discriminating peaks that
      can adequately distinguish between benign and malignant prostate conditions, and
      identify the peaks' underlying biomolecules. METHODS: Twenty-five participants
      with prostate cancer (PCa) and 27 participants with a variety of benign prostatic
      conditions as confirmed by a 10-core tissue biopsy were included. Pre- and post
      DRE urine samples were prepared for MALDI MS profiling using an automated clean
      up procedure. Following mass spectra collection and processing, peak mass and
      intensity were extracted and subjected to statistical analysis to identify peaks
      capable of distinguishing between benign and cancer. Logistic regression was used
      to combine markers to create a sensitive and specific test. RESULTS: A peak at
      m/z 10,760 was identified as beta-microseminoprotein (beta-MSMB) and found to be
      statistically lower in urine from PCa participants using the peak's average
      areas. By combining serum prostate-specific antigen (PSA) levels with MALDI MS
      measured beta-MSMB levels, optimum threshold values obtained from Receiver
      Operator characteristics curves gave an increased sensitivity of 96% at a
      specificity of 26%. CONCLUSIONS: These results demonstrate that with a simple
      sample clean-up followed by MALDI MS profiling, significant differences of MSMB
      abundance were found in post-DRE urine samples. In combination with PSA serum
      levels, obtained from a classic clinical assay led to high classification
      accuracy for PCa in the studied sample set. Our results need to be validated in a
      larger multicenter prospective randomized clinical trial.

PMID- 24115269
TI  - p16 status, pathologic and clinical characteristics, biomolecular signature, and
      long-term outcomes in head and neck squamous cell carcinomas of unknown primary.
AB  - BACKGROUND: The purpose of this study was to report associations between p16
      status, clinicopathologic characteristics, and outcomes for head and neck
      squamous cell carcinoma of unknown primary (CUP). METHODS: Specimens of squamous
      cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16
      stain. A tissue microarray (TMA) was constructed to evaluate biomarkers
      potentially prognostic in head and neck squamous cell carcinoma (HNSCC). RESULTS:
      A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic
      factors benefiting survival were p16+ status (p < .0001), absence of macroscopic
      extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade
      (p = 0.007). The prognostic implication of worse overall survival (OS) with
      macroscopic ECE (p = .009) remained significant when limited to patients who were
      p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a
      biomolecular difference between squamous cell CUP and known-primary cancer.
      CONCLUSION: The majority of patients with squamous cell CUP were p16+, indicative
      of HPV association. P16 staining and ECE seem to be the most prognostic features
      in squamous cell CUP.

PMID- 24115270
TI  - Why buy a PET/MR for high end research?

PMID- 24115271
TI  - Analysis of the effect of occupational exposure to asbestos based on threshold
      regression modeling of case-control data.
AB  - We analyze the effect of occupational exposure to asbestos on the occurrence of
      lung cancer based on a recent French case-control (CC) study. We build a large
      collection of threshold regression models, data-adaptively select a better model
      by CC-weighted likelihood-based cross-validation and then fit this better model
      by CC-weighted maximum likelihood. The CC-weighting allows us to draw valid
      inferences from CC data without relying on a logistic regression. This is
      possible because the joint distribution of the indicator of being a case and
      matching variable is available beforehand owing to two studies independent from
      our data set. The implications of the fitted model in terms of years of life free
      of lung cancer lost due to the exposure to asbestos are discussed. 

PMID- 24115272
TI  - Revival of the R-group approach: a "CTA-shuttled" grafting from approach for well
      defined cylindrical polymer brushes via RAFT polymerization.
AB  - The synthesis of well-defined cylindrical polymer brushes (CPBs) from a linear
      polymer backbone with a high density of RAFT functionalities ("grafting from"
      approach) is challenging when the chain transfer agent (CTA) is attached to the
      backbone via its R-group. It is proposed that the difficulties of the R-group
      approach in controlling the grafting polymerization are induced by the
      "entrapment" of active free radicals within individual growing CPBs. A facile
      "CTA-shuttled" R-group approach overcoming this entrapment effect is developed,
      and used to synthesize well-defined CPBs with polystyrene or poly(tert-butyl
      acrylate) branches and core-shell CPBs with polystyrene-block-poly(N
      isopropylacrylamide) branches. The polydispersity index (PDI = 1.23) of the
      obtained CPBs with polystyrene branches is much lower than that from the
      conventional R-group approach (PDI = 2.18). Monte Carlo simulations confirm that
      the advantage of the "CTA-shuttled" R-group approach consists in the release of
      the active radicals from the trapping CPB systems. 

PMID- 24115273
TI  - Solvent additive to achieve highly ordered nanostructural semicrystalline DPP
      copolymers: toward a high charge carrier mobility.
AB  - A facile spin-coating method in which a small percentage of the solvent additive,
      1-chloronaphthalene (CN), is found to increase the drying time during film
      deposition, is reported. The field-effect mobility of a PDPPDBTE film cast from a
      chloroform-CN mixed solution is 0.46 cm(2) V(-1) s(-1). The addition of CN to the
      chloroform solution facilitates the formation of highly crystalline polymer
      structures.

PMID- 24115274
TI  - Diarylated bi(thieno[2,3-c]thiophene)s: a ring-fusing strategy for controlling
      the molecular alignment of oligoarenes.

PMID- 24115275
TI  - Nanoscale confinement controls the crystallization of calcium phosphate:
      relevance to bone formation.
AB  - A key feature of biomineralization processes is that they take place within
      confined volumes, in which the local environment can have significant effects on
      mineral formation. Herein, we investigate the influence of confinement on the
      formation mechanism and structure of calcium phosphate (CaP). This is of
      particular relevance to the formation of dentine and bone, structures of which
      are based on highly mineralized collagen fibrils. CaP was precipitated within 25
      300 nm diameter, cylindrical pores of track etched and anodised alumina membranes
      under physiological conditions, in which this system enables systematic study of
      the effects of the pore size in the absence of a structural match between the
      matrix and the growing crystals. Our results show that the main products were
      polycrystalline hydroxapatite (HAP) rods, together with some single crystal
      octacalcium phosphate (OCP) rods. Notably, we demonstrate that these were
      generated though an intermediate amorphous calcium phosphate (ACP) phase, and
      that ACP is significantly stabilised in confinement. This effect may have
      significance to the mineralization of bone, which can occur through a transient
      ACP phase. We also show that orientation of the HAP comparable, or even superior
      to that seen in bone can be achieved through confinement effects alone. Although
      this simple experimental system cannot be considered, a direct mimic of the in
      vivo formation of ultrathin HAP platelets within collagen fibrils, our results
      show that the effects of physical confinement should not be neglected when
      considering the mechanisms of formation of structures, such as bones and teeth. 

PMID- 24115277
TI  - Thromboxane A2 receptor alpha promotes tumor growth through an autoregulatory
      feedback pathway.
AB  - Tobacco smoking can cause a number of cancers. The role of thromboxane synthase
      (TxAS) in smoking-related cancers is largely unknown. In this study, 37 pairs of
      tumor and non-tumor lung tissues of non-small-cell lung cancer, 5 lung cancer
      cell lines, and a mouse tumor model were used to study TxAS and its related
      molecules. A mouse model of smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-1
      butanone (NNK)-induced lung tumor showed an increase in TxAS. Thromboxane A2
      receptor (TP) was aberrant in lung cancer tissues of smokers. TxAS and TP were
      increased in lung tissues of NNK-treated mice. The in vitro studies showed that
      TPalpha rather than TPbeta promoted tumor growth, and NNK increased TPalpha. NNK
      induced TxAS, which depended on activation of cyclooxygenase-2 (COX-2), ERK and
      NF-kappaB, could be inhibited by miR-34b/c. TPalpha played a positive role in NNK
      induced COX-2/ERK/NF-kappaB activation, leading to the upregulation of TxAS
      expression and thromboxane A2 (TxA2) synthesis. The newly synthesized TxA2 could
      further activate TPalpha, forming an autoregulatory feedback loop for TPalpha
      activation. Collectively, NNK promotes lung tumor growth via inducing TxAS and
      TPalpha, which constitutes an auto-positive feedback loop to exaggerate the
      growth. This study suggests that TPalpha and TxAS are the ideal targets against
      smoking-related lung cancer. 

PMID- 24115278
TI  - Developing porous honeycomb films using miktoarm star copolymers and exploring
      their application in particle separation.
AB  - This paper reports for the first time the synthesis and application of miktoarm
      star copolymers to produce highly ordered honeycomb films using the breath figure
      technique. Miktoarm star copolymer containing a cross-linked core and two arm
      species, e.g., polystyrene and poly(t-butyl acrylate), is successfully
      synthesized using ATRP in a one-pot arm-first method. Various experimental
      parameters, including polymer architectures, solvents, polymer concentrations,
      and substrates, are explored to investigate their effects on the structure of the
      honeycomb films. It is found that miktoarm star copolymers with high molecular
      weight and spherical shape could readily produce ordered honeycomb films in a
      broader range of concentrations and humidity than linear block copolymers with
      similar chemical compositions but lower molecular weight. Partial hydrolysis of
      poly(t-butyl acrylate) arm species in the honeycomb film transforms the surface
      property from hydrophobic to hydrophilic while maintaining the film's mechanical
      stability in water. This porous monolayer film with uniform pore size
      distribution and inter-connected pore channels is successfully applied for
      separation of microparticles with different sizes. 

PMID- 24115276
TI  - The regulation and deregulation of Wnt signaling by PARK genes in health and
      disease.
AB  - Wingless/Int (Wnt) signaling pathways are signal transduction mechanisms that
      have been widely studied in the field of embryogenesis. Recent work has
      established a critical role for these pathways in brain development, especially
      of midbrain dopaminergic neurones. However, the fundamental importance of Wnt
      signaling for the normal function of mature neurones in the adult central nervous
      system has also lately been demonstrated by an increasing number of studies.
      Parkinson's disease (PD) is the second most prevalent neurodegenerative disease
      worldwide and is currently incurable. This debilitating disease is characterized
      by the progressive loss of a subset of midbrain dopaminergic neurones in the
      substantia nigra leading to typical extrapyramidal motor symptoms. The aetiology
      of PD is poorly understood but work performed over the last two decades has
      identified a growing number of genetic defects that underlie this condition. Here
      we review a growing body of data connecting genes implicated in PD--most notably
      the PARK genes--with Wnt signaling. These observations provide clues to the
      normal function of these proteins in healthy neurones and suggest that
      deregulated Wnt signaling might be a frequent pathomechanism leading to PD. These
      observations have implications for the pathogenesis and treatment of
      neurodegenerative diseases in general.

PMID- 24115279
TI  - Frustrated Lewis pair catalyzed hydroamination of terminal alkynes.
AB  - Catalytic amounts of the Lewis acid B(C6 F5 )3 enable the hydroamination of
      terminal alkynes by aryl amines to the corresponding enamines. In accord with the
      results of stoichiometric reactions, the mechanism of this reaction involves a
      frustrated Lewis pair (FLP). The hydroamination can be followed by an FLP
      catalyzed hydrogenation, resulting in a one-pot stepwise synthesis of amine
      derivatives. 

PMID- 24115280
TI  - Both expression of cytokines and posterior annulus fibrosus rupture are essential
      for pain behavior changes induced by degenerative intervertebral disc: An
      experimental study in rats.
AB  - The aim of this study was to analyze the relationship between intervertebral disc
      degeneration and low back pain (LBP). Rat L4/5 disc degeneration model was
      established by annular puncture using a 0.4 mm needle anteriorly or posteriorly.
      In both anterior and posterior puncture models, magnetic resonance imaging (MRI)
      and histological analyses revealed marked disc degeneration 2 weeks after
      puncture. Cytokine expression was up-regulated in different level in nucleus
      pulposus (NP) from 3 days after puncture. Pain behavioral tests indicated that
      the anterior disc puncture did not induce pain behavior changes, whereas the
      posterior disc puncture resulted in mechanical allodynia from 1 day to 21 days
      after injury. Besides, cytokine expression was significantly increased in dorsal
      root ganglion (DRG) at 1 and 2 weeks after posterior puncture, but not after the
      anterior puncture. These findings indicate the NP of the degenerative disc
      expresses different levels of inflammatory cytokines, and posterior disc puncture
      produced mechanical allodynia. The expression phase of cytokines in the NP was
      accordance with mechanical hyperalgesia in the posterior disc puncture model.
      Both expression of cytokines and posterior annulus fibrosus (AF) rupture in
      degenerative intervertebral disc are essential for pain behavior changes.

PMID- 24115282
TI  - C-C fragmentation: origins and recent applications.
AB  - It has been 60 years since Eschenmoser and Frey disclosed the archetypal C?C
      fragmentation reaction. New fragmentations and several variants of the original
      quickly followed. Many of these variations, which include the Beckmann, Grob,
      Wharton, Marshall, and Eschenmoser-Tanabe fragmentations, have been reviewed over
      the intervening years. A close examination of the origins of fragmentation has
      not been described. Recently, useful new methods have flourished, particularly
      fragmentations that give alkynes and allenes, and such reactions have been
      applied to a range of complex motifs and natural products. This Review traces the
      origins of fragmentation reactions and provides a summary of the methods,
      applications, and new insights of heterolytic C?C fragmentation reactions
      advanced over the last 20 years. 

PMID- 24115281
TI  - Characterization of a high-spin non-heme {FeNO}(8) complex: implications for the
      reactivity of iron nitroxyl species in biology.
AB  - Stable but able: Chemical and electrochemical reduction of a five-coordinate high
      spin non-heme {FeNO}(7) complex (see structure: N blue, Fe orange, and O red)
      generated the first stable high-spin (S=1) non-heme {FeNO}(8) model complex. The
      finding that the reduction is metal-centered and causes a decrease in Fe?NO
      covalency indicates that in biological systems, reduction activates stable non
      heme Fe?NO units for further transformations. 

PMID- 24115283
TI  - Toxicity associated with repeated administration of artemether-lumefantrine in
      rats.
AB  - Chemotherapy remains an important approach in the fight against malaria.
      Artemether-lumefantrine combination is widely in use due to its effectiveness
      against Plasmodium falciparum. Misuse in the form of multiple repeated doses of
      this anti-malaria drug is rampant in Nigeria. This study was designed to assess
      the hepatotoxic and clastogenic potential of extreme misuse of artemether
      lumefantrine in rats. Graded doses of artemether-lumefantrine (1-5 mg/kg body
      weight) were administered by oral gavage for 6 weeks, twice daily, for 3
      consecutive days per week. Artemether-lumefantrine, at all doses, did not have
      significant effects on the body and relative liver weight of treated group
      compared to the negative control group. The mean gamma-glutamyltransferase,
      alanine, and aspartate aminotransaminase activity in groups of artemether
      lumefantrine treated rats were significantly higher (p < 0.05) than that of the
      negative control group indicating that repeated administration of artemether
      lumefantrine may be hepatotoxic. Findings from histological analyses of liver
      cross-section support the enzyme pattern of hepatoxicity. In addition, the drug,
      at all experimental doses, significantly induced (p < 0.05) formation of
      micronucleated polychromatic erythrocytes in the bone marrow cells of the treated
      rats compared with the negative control indicating clastogenic potential of the
      drug when misused.

PMID- 24115285
TI  - Van der Waals epitaxial double heterostructure: InAs/single-layer graphene/InAs.
AB  - Van der Waals (vdW) epitaxial double heterostructures have been fabricated by vdW
      epitaxy of InAs nanostructures on both sides of graphene. InAs nanostructures
      diametrically form on/underneath graphene exclusively along As-polar direction,
      indicating polarity inversion of the double heterostructures. First-principles
      and density functional calculations demonstrate how and why InAs easily form to
      be double heterostructures with polarity inversion. 

PMID- 24115286
TI  - Aerobic vs. anaerobic scope: sibling species of fish indicate that temperature
      dependence of hypoxia tolerance can predict future survival.
AB  - The temperature dependence of aerobic scope has been suggested to be a major
      determinant of how marine animals will cope with future rises in environmental
      temperature. Here, we present data suggesting that in some animals, the
      temperature dependence of anaerobic scope (i.e., the capacity for surviving
      severe hypoxia) may determine present-day latitudinal distributions and potential
      for persistence in a warmer future. As a model for investigating the role of
      anaerobic scope, we studied two sibling species of coral-dwelling gobies,
      Gobiodon histrio, and G. erythrospilus, with different latitudinal distributions,
      but which overlap in equal abundance at Lizard Island (14 degrees 40'S) on the
      Great Barrier Reef. These species did not differ in the temperature dependence of
      resting oxygen consumption or critical oxygen concentration (the lowest oxygen
      level where resting oxygen consumption can be maintained). In contrast, the more
      equatorial species (G. histrio) had a better capacity to endure anaerobic
      conditions at oxygen levels below the critical oxygen concentration at the high
      temperatures (32-33  degrees C) more likely to occur near the equator, or in a
      warmer future. These results suggest that anaerobic scope, in addition to aerobic
      scope, could be important in determining the impacts of global warming on some
      marine animals. 

PMID- 24115287
TI  - Optical bioassay for measuring sublethal toxicity of insecticides in Daphnia
      pulex.
AB  - Many emerging contaminants tend to be biologically active at very low
      concentrations, occur in water as part of complex mixtures, and impact biota in
      ways that are not detected using traditional toxicity tests (e.g., median lethal
      concentration). To evaluate emerging contaminants, the authors developed a method
      for detecting sublethal behavioral effects by quantifying the swimming behavior
      of Daphnia pulex, a model organism for studying aquatic toxicity. This optical
      tracking technique is capable of measuring many swimming parameters, 2 of which
      cumulative distance and angular change-are presented. To validate this technique,
      2 prototypical compounds that exhibit different modes of action as well as
      corresponding insecticides that are commonly found in surface waters were
      investigated. The acetylcholinesterase (AChE) inhibitor physostigmine was used as
      the prototypical compound for the large number of AChE inhibitor insecticides
      (e.g., chlorpyrifos). Nicotine was used as the prototypical compound for
      neonicotinoid insecticides (e.g., imidacloprid). Results demonstrate that this
      assay is capable of detecting sublethal behavioral effects that are concentration
      dependent and that insecticides with the same mode of action yield similar
      results. The method can easily be scaled up to serve as a high-throughput
      screening tool to detect sublethal toxic effects of a variety of chemicals. This
      method is likely to aid in enhancing the current understanding of emerging
      contaminants and to serve as a novel water-quality screening tool.

PMID- 24115289
TI  - Are improvements in shame and self-compassion early in eating disorders treatment
      associated with better patient outcomes?
AB  - Compassion-focused therapy (CFT; Gilbert, 2005, 2009) is a transdiagnostic
      treatment approach focused on building self-compassion and reducing shame. It is
      based on the theory that feelings of shame contribute to the maintenance of
      psychopathology, whereas self-compassion contributes to the alleviation of shame
      and psychopathology. We sought to test this theory in a transdiagnostic sample of
      eating disorder patients by examining whether larger improvements in shame and
      self-compassion early in treatment would facilitate faster eating disorder
      symptom remission over 12 weeks. Participants were 97 patients with an eating
      disorder admitted to specialized day hospital or inpatient treatment. They
      completed the Eating Disorder Examination-Questionnaire, Experiences of Shame
      Scale, and Self-Compassion Scale at intake, and again after weeks 3, 6, 9, and
      12. Multilevel modeling revealed that patients who experienced greater decreases
      in their level of shame in the first 4 weeks of treatment had faster decreases in
      their eating disorder symptoms over 12 weeks of treatment. In addition, patients
      who had greater increases in their level of self-compassion early in treatment
      had faster decreases in their feelings of shame over 12 weeks, even when
      controlling for their early change in eating disorder symptoms. These results
      suggest that CFT theory may help to explain the maintenance of eating disorders.
      Clinically, findings suggest that intervening with shame early in treatment,
      perhaps by building patients' self-compassion, may promote better eating
      disorders treatment response.

PMID- 24115288
TI  - Genetic basis of congenital erythrocytosis: mutation update and online databases.
AB  - Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and
      heterogeneous clinical entity. It is caused by deregulated red blood cell
      production where erythrocyte overproduction results in elevated hemoglobin and
      hematocrit levels. Primary congenital familial erythrocytosis is associated with
      low erythropoietin (Epo) levels and results from mutations in the Epo receptor
      gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and
      results in increased Epo production. These include hemoglobin variants with
      increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3
      bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in
      the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected
      gene, CE can be inherited either in an autosomal dominant or recessive mode, with
      sporadic cases arising de novo. Despite recent important discoveries in the
      molecular pathogenesis of CE, the molecular causes remain to be identified in
      about 70% of the patients. With the objective of collecting all the published and
      unpublished cases of CE the COST action MPN&MPNr-Euronet developed a
      comprehensive Internet-based database focusing on the registration of clinical
      history, hematological, biochemical, and molecular data
      (http://www.erythrocytosis.org/). In addition, unreported mutations are also
      curated in the corresponding Leiden Open Variation Database. 

PMID- 24115290
TI  - Concise review: bridging the gap: bone regeneration using skeletal stem cell
      based strategies - where are we now?
AB  - Skeletal stem cells confer to bone its innate capacity for regeneration and
      repair. Bone regeneration strategies seek to harness and enhance this
      regenerative capacity for the replacement of tissue damaged or lost through
      congenital defects, trauma, functional/esthetic problems, and a broad range of
      diseases associated with an increasingly aged population. This review describes
      the state of the field and current steps to translate and apply skeletal stem
      cell biology in the clinic and the problems therein. Challenges are described
      along with key strategies including the isolation and ex vivo expansion of
      multipotential populations, the targeting/delivery of regenerative populations to
      sites of repair, and their differentiation toward bone lineages. Finally,
      preclinical models of bone repair are discussed along with their implications for
      clinical translation and the opportunities to harness that knowledge for
      musculoskeletal regeneration.

PMID- 24115291
TI  - The effect of long-term relocation on child and adolescent survivors of Hurricane
      Katrina.
AB  - The current study is designed to increase knowledge of the effects of relocation
      and its association with longer-term psychological symptoms following disaster.
      Following clinical observations and in discussions held with school officials
      expressing concerns about relocated students, it was hypothesized that students
      who relocated to a different city following Hurricane Katrina in 2005 would have
      more symptoms of posttraumatic stress compared to students who returned to New
      Orleans. The effect of Hurricane Katrina relocation was assessed on a sample of
      child and adolescent survivors in 5th through 12th grades (N = 795). Students
      with Orleans Parish zip codes prior to Hurricane Katrina were categorized into
      relocation groupings: (a) relocated to Baton Rouge, (b) returned to prior zip
      code, and (c) moved to a different zip code within Orleans Parish. Overall
      results revealed more trauma symptoms for relocated students. Results also
      revealed that younger relocated students had fewer symptoms compared to older
      students. The opposite was found for students who returned to their same zip
      code, with older students having fewer symptoms. This study supports the need for
      school-based services not only in disaster areas, but also in schools where
      survivors tend to migrate. 

PMID- 24115292
TI  - A role for the endocannabinoid system in exercise-induced spatial memory
      enhancement in mice.
AB  - It is well known that physical exercise has positive effects on cognitive
      functions and hippocampal plasticity. However, the underlying mechanisms have
      remained to be further investigated. Here we investigated the hypothesis that the
      memory-enhancement promoted by physical exercise relies on facilitation of the
      endocannabinoid system. We observed that the spatial memory tested in the object
      location paradigm did not persist in sedentary mice, but could be improved by 1
      week of treadmill running. In addition, exercise up-regulated CB1 receptor and
      BDNF expression in the hippocampus. To verify if these changes required CB1
      activation, we treated the mice with the selective antagonist, AM251, before each
      period of physical activity. In line with our hypothesis, this drug prevented the
      exercise-induced memory enhancement and BDNF expression. Furthermore, AM251
      reduced CB1 expression. To test if facilitating the endocannabinoid system
      signaling would mimic the alterations observed after exercise, we treated
      sedentary animals during 1 week with the anandamide-hydrolysis inhibitor, URB597.
      Mice treated with this drug recognized the object in a new location and have
      increased levels of CB1 and BDNF expression in the hippocampus, showing that
      potentiating the endocanabinoid system equally benefits memory. In conclusion,
      the favorable effects of exercise upon spatial memory and BDNF expression depend
      on facilitation of CB1 receptor signaling, which can be mimic by inhibition of
      anandamide hydrolysis in sedentary animals. Our results suggest that, at least in
      part, the promnesic effect of the exercise is dependent of CB1 receptor
      activation and is mediated by BDNF.

PMID- 24115295
TI  - The aminocyclodextrin/Pd(OAc)2 complex as an efficient catalyst for the Mizoroki
      Heck cross-coupling reaction.
AB  - An aminocyclodextrin/Pd(OAc)2 complex is used as an efficient, reusable catalyst
      in the Mizoroki-Heck reaction of aryl halides/triflates with olefins to give
      carbon-carbon-coupled products in good to excellent yields. This simple,
      efficient catalytic system is applicable to a wide range of aryl and heteroaryl
      halides/triflates and olefins. This environmentally benign procedure is less
      hazardous, milder, uses a catalytic amount of ligand and Pd(OAc)2 , avoids an
      inert atmosphere, and catalyst recovery and reusability are achieved. 

PMID- 24115294
TI  - NF-kappaB RelB negatively regulates osteoblast differentiation and bone
      formation.
AB  - RelA-mediated NF-kappaB canonical signaling promotes mesenchymal progenitor cell
      (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and
      thus negatively regulates bone formation. Previous studies suggest that NF-kappaB
      RelB may also negatively regulate bone formation through noncanonical signaling,
      but they involved a complex knockout mouse model, and the molecular mechanisms
      involved were not investigated. Here, we report that RelB(-/-) mice develop age
      related increased trabecular bone mass associated with increased bone formation.
      RelB(-/-) bone marrow stromal cells expanded faster in vitro and have enhanced OB
      differentiation associated with increased expression of the osteoblastogenic
      transcription factor, Runt-related transcription factor 2 (Runx2). In addition,
      RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly,
      RelB(-/-) bone-derived MPCs formed bone more rapidly than wild-type cells after
      they were injected into a murine tibial bone defect model. Our findings indicate
      that RelB negatively regulates bone mass as mice age and limits bone formation in
      healing bone defects, suggesting that inhibition of RelB could reduce age-related
      bone loss and enhance bone repair.

PMID- 24115297
TI  - Abstracts of the 29th International Conference on Pharmacoepidemiology &
      Therapeutic Risk Management. August 25-28, 2013. Montreal, Canada.

PMID- 24115296
TI  - Improved renal function in liver transplant recipients treated for hepatitis C
      virus with a sustained virological response and mild chronic kidney disease.
AB  - Hepatitis C virus (HCV) is associated with renal complications. We aimed to
      determine whether a sustained virological response (SVR) was associated with
      improvements in renal function (RF) in liver transplant (LT) recipients treated
      for HCV. Changes in RF were compared 1, 3, and 5 years after therapy as a
      function of the stage of chronic kidney disease (CKD) before treatment (BT).
      Variables associated with renal dysfunction [RD; 4-variable Modification of Diet
      in Renal Disease (MDRD-4) value 60 mL/minute] at the last follow-up (LFU) were
      evaluated for all treated LT patients with a minimum follow-up of at least 1 year
      since the end of treatment (EOT; n = 175). There were 99 patients with stage 2
      CKD BT (MDRD-4 value 60-89 mL/minute/1.73 m(2) ), and an improvement in RF was
      observed more frequently among SVR patients versus nonresponders (NRs). The
      median changes in the MDRD-4 values BT to 1, 3, and 5 years after treatment were 
      0.5, 4.5, and 9.4 mL/minute for the SVR patients and -1, -0.3, and -1.5 mL/minute
      for the NRs (P = 0.61, P = 0.06, and P = 0.004, respectively). RD was present in
      31% of the patients at the LFU at a median of 3.8 years after EOT (range 1-9
      years). The follow-up did not differ between SVR patients and NRs. RD was present
      at the LFU in 19% of SVR patients versus 40% of NRs (P = 0.002). In the
      multivariate analysis, RD at the LFU was associated with NRs [relative risk (RR)
      3.8, 95% confidence interval (CI)  = 1.3-11.23, P = 0.01], EOT MDRD-4 values (RR
      = 1.022, 95% CI = 1.001-1.04, P = 0.04), and female sex (RR = 5.6, 95% CI = 1.84
      17.5, P = 0.002). In conclusion, SVR leads to improved RF in HCV-infected LT
      recipients with stage 2 CKD BT.

PMID- 24115298
TI  - Enantioselective copper-catalyzed [3+3] cycloaddition of azomethine ylides with
      azomethine imines.

PMID- 24115299
TI  - Combination of very low energy diets and pharmacotherapy in the treatment of
      obesity: meta-analysis of published data.
AB  - Obesity has reached epidemic proportions globally, with more than 1 billion
      adults overweight - at least 300 million of them clinically obese - and is a
      major contributor to the global burden of chronic disease (heart disease and
      diabetes) and disability. The aim of the study was to perform a systematic review
      and meta-analysis of published data on the combination of very low energy diets
      also known as very low calorie diets and pharmacotherapy for its effectiveness in
      the treatment of obesity. A MEDLINE (Pubmed) search from 1970 to 2009 using
      multiple combinations of the relevant terms was carried out; the matching
      articles were also searched for additional references. Meta-analysis tools were
      used to summarize results. Only randomized controlled trials that compared
      pharmacotherapy with placebo after a very low energy diet period were selected,
      and six articles were finally considered to be appropriate for evaluation. The
      combination of very low energy diet and pharmacotherapy was found to be effective
      for people with obesity in clinical trials. The net effect of 6.1 kg placebo
      subtracted weight loss after 1 year represents a clinically meaningful result
      that is comparable with the effect of drugs given at the start of a weight loss
      programme. The present meta-analysis contributes to the understanding that
      combination therapies are expected to achieve greater weight loss than
      monotherapy; grasping this understanding, researcher has introduced newer anti
      obesity pharmacological approaches have embraced combination therapies.

PMID- 24115300
TI  - Efficient separation of photogenerated electron-hole pairs by the combination of
      a heterolayered structure and internal polar field in pyroelectric BiOIO3
      nanoplates.

PMID- 24115301
TI  - Psychiatric and physical sequelae of childhood physical and sexual abuse and
      forced sexual trauma among individuals with serious mental illness.
AB  - Trauma and posttraumatic stress disorder (PTSD) frequently co-occur with serious
      mental illness, yet the unique mental and physical health influences of childhood
      physical abuse (CPA), childhood sexual abuse (CSA), and forced sexual trauma on
      individuals with serious mental illness remain unevaluated. The present study of
      172 individuals with serious mental illness investigated the adverse effects of
      CPA, CSA, and forced sexual trauma on severity of PTSD and depression, and
      overall mental and physical health functioning. Data analysis consisted of chi
      square tests, independent t tests, bivariate odds ratios, and linear regressions.
      Prevalence of CPA (44.8%), CSA (29.1%), and forced sexual trauma (33.1%) were
      elevated, and nearly one third of participants (31.4%) reported clinical PTSD.
      Participants exposed to CSA or forced sexual trauma evidenced bivariate ORs
      ranging from 4.13 to 7.02 for PTSD, 2.44 to 2.50 for major depression, and 2.14
      to 2.31 for serious physical illness/disability. Sexual trauma exposure
      associated with heightened PTSD and depression, and reduced mental and physical
      health functioning, with CSA uniquely predicting PTSD, depression, and physical
      health difficulties. CPA less significantly affected these clinical domains.
      Sexual traumas have profound negative effects on mental and physical health
      outcomes among individuals with serious mental illness; increased screening and
      treatment of sexual traumas is needed. 

PMID- 24115302
TI  - Unusual forest growth decline in boreal North America covaries with the retreat
      of Arctic sea ice.
AB  - The 20th century was a pivotal period at high northern latitudes as it marked the
      onset of rapid climatic warming brought on by major anthropogenic changes in
      global atmospheric composition. In parallel, Arctic sea ice extent has been
      decreasing over the period of available satellite data records. Here, we document
      how these changes influenced vegetation productivity in adjacent eastern boreal
      North America. To do this, we used normalized difference vegetation index (NDVI)
      data, model simulations of net primary productivity (NPP) and tree-ring width
      measurements covering the last 300 years. Climatic and proxy-climatic data sets
      were used to explore the relationships between vegetation productivity and Arctic
      sea ice concentration and extent, and temperatures. Results indicate that an
      unusually large number of black spruce (Picea mariana) trees entered into a
      period of growth decline during the late-20th century (62% of sampled trees; n =
      724 cross sections of age >70 years). This finding is coherent with evidence
      encoded in NDVI and simulated NPP data. Analyses of climatic and vegetation
      productivity relationships indicate that the influence of recent climatic changes
      in the studied forests has been via the enhanced moisture stress (i.e. greater
      water demands) and autotrophic respiration amplified by the declining sea ice
      concentration in Hudson Bay and Hudson Strait. The recent decline strongly
      contrasts with other growth reduction events that occurred during the 19th
      century, which were associated with cooling and high sea ice severity. The recent
      decline of vegetation productivity is the first one to occur under circumstances
      related to excess heat in a 300-year period, and further culminates with an
      intensifying wildfire regime in the region. Our results concur with observations
      from other forest ecosystems about intensifying temperature-driven drought stress
      and tree mortality with ongoing climatic changes. 

PMID- 24115303
TI  - Bioinspired iron-based catalyst for atom transfer radical polymerization.

PMID- 24115304
TI  - Organocatalytic asymmetric conjugate addition of aldehydes to nitroolefins:
      identification of catalytic intermediates and the stereoselectivity-determining
      step by ESI-MS.

PMID- 24115305
TI  - Assessing global and gene specific DNA methylation in anorexia nervosa: a pilot
      study.
AB  - OBJECTIVE: At present there are no genome-wide methylation data available in
      anorexia nervosa (AN) and no studies have examined the potential dynamic nature
      of DNA methylation during treatment, so it is unclear whether epigenetic
      disruption established over long periods of malnourishment is reversible. The
      current study examined global levels of DNA methylation and methylation at a
      labile imprinted locus in women with AN. METHOD: Buccal swabs were collected from
      10 women who were admitted to hospital for treatment of AN and 10 age-matched
      healthy controls DNA methylation of LINE-1 repetitive elements and the H19
      imprinting control region was measured using previously validated assays using
      the Sequenom Mass Array platform. RESULTS: No evidence for altered global or gene
      specific DNA methylation was observed in association with AN. DISCUSSION: Larger,
      genome-wide studies of epigenetic modifications, encompassing both DNA
      methylation and other epigenetic marks, are required to determine the degree to
      which AN is associated with specific epigenetic changes, potentially modifiable
      through appropriate treatments that improve nutrition.

PMID- 24115306
TI  - Breath figure arrays: unconventional fabrications, functionalizations, and
      applications.
AB  - A breath figure (BF) is the water droplet array that forms when moisture comes in
      contact with a cold substrate. This water droplet array has been widely utilized
      in the past two decades as a versatile soft template for the fabrication of
      polymeric porous films. Accordingly, the ordered pores on the polymer films
      formed with such a method are named a breath figure array (BFA).The BF templating
      technique is undergoing rapid development. Several unconventional BF processes
      have been established to prepare porous films with unique morphologies or primary
      materials, and various newly developed functionalization techniques have
      significantly improved the performance of polymeric films with BFA, leading to
      novel applications, including templates, biosensors, and separation membranes.
      These recent achievements will be described in this Minireview. 

PMID- 24115307
TI  - Reconstruction of two separate defects in the upper extremity using anterolateral
      thigh chimeric flap.
AB  - We presented our experience on the use of anterolateral thigh (ALT) chimeric flap
      to reconstruct two separate defects in upper extremity. From December 2009 to
      August 2012, we used this ALT chimeric flap to reconstruct two separate defects
      in upper extremity on five patients (mean age: 36.6 years; range: 15 ~ 47 years).
      The locations of defect were palm and fingers in four patients and forearm in the
      other patient. The sizes of defect ranged from 4.5 * 1.5 cm to 20 * 10 cm. A
      minimum of two separate perforator vessels in the flap were identified. The skin
      paddle was then split between the two perforators to shape two separate paddles
      with a common vascular supply. There were no cases of flap failure or re
      exploration. Four donor sites were directly closed and one was covered by a skin
      graft. Donor-site morbidity was negligible. The ALT chimeric flap provides
      customized cover for two separate defects in upper extremity.

PMID- 24115309
TI  - Nanotubular crosstalk with distressed cardiomyocytes stimulates the paracrine
      repair function of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) are known to repair broken heart tissues primarily
      through a paracrine fashion while emerging evidence indicate that MSC can
      communicate with cardiomyocytes (CM) through tunneling nanotubes (TNT).
      Nevertheless, no link has been so far established between these two processes.
      Here, we addressed whether cell-to-cell communication processes between MSC and
      suffering cardiomyocytes and more particularly those involving TNT control the
      MSC paracrine regenerative function. In the attempt to mimic in vitro an injured
      heart microenvironment, we developed a species mismatch coculture system
      consisting of terminally differentiated CM from mouse in a distressed state and
      human multipotent adipose derived stem cells (hMADS). In this setting, we found
      that crosstalk between hMADS and CM through TNT altered the secretion by hMADS of
      cardioprotective soluble factors such as VEGF, HGF, SDF-1alpha, and MCP-3 and
      thereby maximized the capacity of stem cells to promote angiogenesis and
      chemotaxis of bone marrow multipotent cells. Additionally, engraftment
      experiments into mouse infarcted hearts revealed that in vitro preconditioning of
      hMADS with cardiomyocytes increased the cell therapy efficacy of naive stem
      cells. In particular, in comparison with hearts treated with stem cells alone,
      those treated with cocultured ones exhibited greater cardiac function recovery
      associated with higher angiogenesis and homing of bone marrow progenitor cells at
      the infarction site. In conclusion, our findings established the first
      relationship between the paracrine regenerative action of MSC and the nanotubular
      crosstalk with CM and emphasize that ex vivo manipulation of these communication
      processes might be of interest for optimizing current cardiac cell therapies.

PMID- 24115308
TI  - Two-stage implantation of the skin- and bone-integrated pylon seeded with
      autologous fibroblasts induced into osteoblast differentiation for direct
      skeletal attachment of limb prostheses.
AB  - Angio- and osteogenesis following the two-stage (TS) implantation of the skin-
      and bone-integrated pylon seeded with autologous fibroblasts was evaluated. Two
      consecutive animal substudies were undertaken: intramedullary subcutaneous
      implantation (15 rabbits) and a TS transcutaneous implantation (12 rabbits). We
      observed enhanced osseointegrative properties of the intramedullary porous
      component seeded with fibroblasts induced into osteoblast differentiation, as
      compared to the untreated porous titanium pylon. The three-phase scintigraphy and
      subsequent histological analysis showed that the level of osteogenesis was 1.5
      fold higher than in the control group, and significantly so (p < 0.05). The
      biocompatibility was further proved by the absence of inflammatory response or
      encapsulation and sequestration on the histology assay. Treatment of the
      transcutaneous component with autologous fibroblasts was associated with nearly a
      2-fold decrease in the period required for the ingrowth of dermal and subdermal
      soft tissues into the implant surface, as compared to the untreated porous
      titanium component. Direct dermal attachment to the transcutaneous implant
      prevented superficial and deep periprosthetic infections in rabbits in vivo.

PMID- 24115310
TI  - Bi-enzyme sensor for phenolic compounds with fluorescent read-out.
AB  - In this paper, the use of tyrosinase (Ty) from Streptomyces antibioticus, labeled
      with a fluorescent tag, in combination with soluble quinoprotein (PQQ-containing)
      glucose dehydrogenase (s-GDH) to measure trace amounts of phenols is explored.
      Proof of concept is provided by a series of experiments, which show a clear
      quantitative dependence of the response on the phenol concentration. One of the
      advantages of the detection system is that apart from a standard fluorimeter no
      further instrumentation is required. 

PMID- 24115312
TI  - S100A6 (calcyclin) is a novel marker of neural stem cells and astrocyte
      precursors in the subgranular zone of the adult mouse hippocampus.
AB  - S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to play
      various roles in the brain, for example, cell proliferation and differentiation,
      calcium homeostasis, and neuronal degeneration. In addition to some limbic
      nuclei, S100A6 is distributed in the rostral migratory stream, one of the major
      neurogenic niches of the adult brain. However, the potential involvement of
      S100A6 in adult neurogenesis remains unclear. In this study, we aimed to
      elucidate the role of S100A6 in the other major neurogenic niche, the subgranular
      zone of the dentate gyrus in the adult mouse hippocampus. Immunofluorescent
      multiple labeling showed that S100A6 was highly expressed in neural stem cells
      labeled by sex determining region Y-box 2, brain lipid-binding protein protein
      and glial fibrillary acidic protein. S100A6+ cells often extended a long process
      typical of radial glial morphology. In addition, S100A6 was found in some
      S100beta+ astrocyte lineage cells. Interestingly, proliferating cell nuclear
      antigen was detected in a fraction of S100A6+/S100beta+ cells. These cells were
      considered to be lineage-restricted astrocyte precursors maintaining mitotic
      potential. On the other hand, S100A6 was rarely seen in neural lineage cells
      labeled by T-box brain protein 2, doublecortin, calretinin and calbindin D28K.
      Cell fate-tracing experiment using BrdU showed that the majority of newly
      generated immature astrocytes were immunoreactive for S100A6, while mature
      astrocytes lacked S100A6 immunoreactivity. Administration of S100 protein
      inhibitor, trifluoperazine, caused a reduction in production of S100beta+
      astrocyte lineage cells, but had no impact on neurogenesis. Overall, our data
      provide the first evidence that S100A6 is a specific marker of neural stem cells
      and astrocyte precursors, and may be especially important for generation of
      astrocytes in the adult hippocampus.

PMID- 24115313
TI  - DNA damage signaling, impairment of cell cycle progression, and apoptosis
      triggered by 5-ethynyl-2'-deoxyuridine incorporated into DNA.
AB  - The "click chemistry" approach utilizing 5-ethynyl-2'-deoxyuridine (EdU) as a DNA
      precursor was recently introduced to assess DNA replication and adapted to flow-
      and imaging-cytometry. In the present study, we observed that EdU, once
      incorporated into DNA, induces DNA damage signaling (DDS) such as phosphorylation
      of ATM on Ser1981, of histone H2AX on Ser139, of p53 on Ser15, and of Chk2 on
      Thr68. It also perturbs progression of cells through the cell cycle and
      subsequently induces apoptosis. These effects were observed in non-small cell
      lung adenocarcinoma A549 as well as in B-cell human lymphoblastoid TK6 and WTK1
      cells, differing in the status of p53 (wt versus mutated). After 1 h EdU pulse
      labeling, the most affected was cells progression through the S phase subsequent
      to that at which they had incorporated EdU. This indicates that DNA replication
      using the template containing incorporated EdU is protracted and triggers DDS.
      Furthermore, progression of cells having DNA pulse-labeled with EdU led to
      accumulation of cells in G2 , likely by activating G2 checkpoint. Consistent with
      the latter was activation of p53 and Chk2. Although a correlation was observed in
      A549 cells between the degree of EdU incorporation and the extent of gammaH2AX
      induction, such correlation was weak in TK6 and WTK1 cells. The degree of
      perturbation of the cell cycle kinetics by the incorporated EdU was different in
      the wt p53 TK6 cells as compared to their sister WTK1 cell line having mutated
      p53. The data are thus consistent with the role of p53 in modulating activation
      of cell cycle checkpoints in response to impaired DNA replication. The confocal
      microscopy analysis of the 3D images of cells exposed to EdU for 1 h pulse and
      then grown for 24 or 48 h revealed an increased number of colocalized gammaH2AX
      and p53BP1 foci considered to be markers of DNA double-strand breaks and enlarged
      nuclei.

PMID- 24115314
TI  - Bolus calculator and wirelessly communicated blood glucose measurement
      effectively reduce hypoglycaemia in type 1 diabetic children - randomized
      controlled trial.
AB  - BACKGROUND: The aim of this study was to assess the effect of bolus calculator
      function and wireless communication between insulin pump and blood glucose metre
      on metabolic control in children with type 1 diabetes, treated with insulin
      pumps. METHODS: In this randomized, controlled, 12-week trial, 156 patients, aged
      12.9 +/- 2.6 years, with a history of diabetes of 5.1 +/- 3.3 years and glycated
      haemoglobin values of 7.3 +/- 1.2% (56.3 +/- 13.44 mmol/mol) were included.
      Children were assigned to one of three arms: group A, subjects using bolus
      calculator and wireless communication between insulin pump and blood glucose
      metre; group B, subjects using bolus calculator without communication between the
      devices and group C, control group. Devices were downloaded at 0, 6 and 12 weeks.
      RESULTS: There were statistically fewer episodes of hypoglycaemia in children
      using bolus calculator compared with the control group: A versus C (3.8 +/- 3.1
      versus 7.8 +/- 5.13 episodes/2 weeks, respectively, p < 0.0001); B versus C (3.6
      +/- 3.3 versus 7.8 +/- 5.1 episodes/2 weeks, respectively, p < 0.0001). Patients
      in group A used bolus calculator function significantly more frequently than
      patients in group B (4.9 +/- 3.4 versus 2.5 +/- 2.9 times/24 h, respectively, p =
      0.0006). No significant differences in glycated haemoglobin levels were found
      between the experimental and the control groups: group A versus C (p = 0.699).
      The use of bolus calculator did not influence post-prandial glycaemia, body mass
      index-SD score or insulin/kg/24 h. CONCLUSIONS: Bolus calculator use reduces
      hypoglycaemic episodes independently of communication between insulin pump and
      blood glucose metre. Wireless communication between devices results in more
      frequent bolus calculator use.

PMID- 24115315
TI  - Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver
      transplantation for unresectable hilar cholangiocarcinoma.
AB  - Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically
      because of its anatomical location and its frequent association with primary
      sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver
      transplantation in lymph node-negative patients has been advanced by select liver
      transplant centers for the treatment of patients with unresectable disease. This
      approach has most commonly used external-beam radiotherapy in combination with
      biliary brachytherapy and 5-fluorouracil-based chemotherapy. Our center recently
      embarked on a protocol using stereotactic body radiation therapy (SBRT) followed
      by capecitabine in lymph node-negative patients until liver transplantation. We,
      therefore, retrospectively determined the tolerability and pathological response
      in this pilot study. During a 3-year period, 17 patients with unresectable hilar
      CCA were evaluated for treatment under this protocol. In all, 12 patients
      qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5
      fractions over the course of 2 weeks). After 1 week of rest, capecitabine was
      initiated at 1330 mg/m(2) /day, and it was continued until liver transplantation.
      During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis
      and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose
      reductions were required on 5 occasions. Ultimately, 9 patients were listed for
      transplantation, and 6 patients received a liver transplant. The explant
      pathology of hilar tumors showed at least a partial treatment response in 5
      patients, with extensive tumor necrosis and fibrosis noted. Additionally, high
      apoptotic indices and low proliferative indices were measured during histological
      examinations. Eleven transplant-related complications occurred, and the 1-year
      survival rate after transplantation was 83%. In this pilot study, neoadjuvant
      therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA
      demonstrated acceptable tolerability. Further studies will determine the overall
      future efficacy of this therapy.

PMID- 24115316
TI  - Congenital heart defects in patients with deletions upstream of SOX9.
AB  - Heterozygous loss-of-function coding-sequence mutations of the transcription
      factor SOX9 cause campomelic dysplasia, a rare skeletal dysplasia with congenital
      bowing of long bones (campomelia), hypoplastic scapulae, a missing pair of ribs,
      pelvic, and vertebral malformations, clubbed feet, Pierre Robin sequence (PRS),
      facial dysmorphia, and disorders of sex development. We report here two unrelated
      families that include patients with isolated PRS, isolated congenital heart
      defect (CHD), or both anomalies. Patients from both families carried a very
      similar ~1 Mb deletion upstream of SOX9. Analysis of ChIP-Seq from mouse cardiac
      tissue for H3K27ac, a marker of active regulatory elements, led us to identify
      several putative cardiac enhancers within the deleted region. One of these
      elements is known to interact with Nkx2.5 and Gata4, two transcription factors
      responsible for CHDs. Altogether, these data suggest that disruption of cardiac
      enhancers located upstream of SOX9 may be responsible for CHDs in humans. 

PMID- 24115318
TI  - Are Food and Drug Administration prescription drug safety plans working? A case
      study of isotretinoin.

PMID- 24115317
TI  - Separating direct and indirect effects of global change: a population dynamic
      modeling approach using readily available field data.
AB  - Two sources of complexity make predicting plant community response to global
      change particularly challenging. First, realistic global change scenarios involve
      multiple drivers of environmental change that can interact with one another to
      produce non-additive effects. Second, in addition to these direct effects, global
      change drivers can indirectly affect plants by modifying species interactions. In
      order to tackle both of these challenges, we propose a novel population modeling
      approach, requiring only measurements of abundance and climate over time. To
      demonstrate the applicability of this approach, we model population dynamics of
      eight abundant plant species in a multifactorial global change experiment in
      alpine tundra where we manipulated nitrogen, precipitation, and temperature over
      7 years. We test whether indirect and interactive effects are important to
      population dynamics and whether explicitly incorporating species interactions can
      change predictions when models are forecast under future climate change
      scenarios. For three of the eight species, population dynamics were best
      explained by direct effect models, for one species neither direct nor indirect
      effects were important, and for the other four species indirect effects mattered.
      Overall, global change had negative effects on species population growth,
      although species responded to different global change drivers, and single-factor
      effects were slightly more common than interactive direct effects. When the
      fitted population dynamic models were extrapolated under changing climatic
      conditions to the end of the century, forecasts of community dynamics and
      diversity loss were largely similar using direct effect models that do not
      explicitly incorporate species interactions or best-fit models; however,
      inclusion of species interactions was important in refining the predictions for
      two of the species. The modeling approach proposed here is a powerful way of
      analyzing readily available datasets which should be added to our toolbox to
      tease apart complex drivers of global change. 

PMID- 24115319
TI  - Highly concave platinum nanoframes with high-index facets and enhanced
      electrocatalytic properties.
AB  - Deeply excavated: Platinum nanoframes with highly concave {740} facets are
      synthesized directly by a facile oleylamine-assisted solvothermal method. Because
      of the unique structure and exposed high-index facets, the as-prepared Pt
      nanoframes exhibit very high electrocatalytic activity and remarkable stability
      for the oxygen reduction reaction and the oxidation of methanol and formic acid. 

PMID- 24115321
TI  - Composition of the bovine uterine proteome is associated with stage of cycle and
      concentration of systemic progesterone.
AB  - Early embryonic loss accounts for over 70% of total embryonic and foetal loss in
      dairy cattle. Early embryonic development and survival is associated with the
      concentration of systemic progesterone. To determine if the uterine proteome is
      influenced by stage of cycle or systemic progesterone concentrations, uterine
      flushings were collected from the ipsi- and contralateral uterine horns of beef
      heifers on Days 7 (n = 10) and 15 (n = 10) of the oestrous cycle. Animals were
      separated into low or high progesterone groups based on plasma progesterone
      concentrations on Day 5 of the cycle. Samples were albumin depleted before iTRAQ
      R labeling and subsequent strong cation exchange-LC-MS/MS analyses. A total of 20
      proteins were up to 5.9-fold higher (p<0.05) and 20 were up to 2.3-fold lower on
      Day 15 compared toDay 7. In addition, the expression of a number of proteins on
      Day 7 and/or 15 of the cycle was correlated with progesterone concentrations
      during Days 3-7 or the rate of change in progesterone between Days 3 and 7. This
      study highlights the dynamic changes occurring in the microenvironment
      surrounding the embryo during this period. The findings here also support the
      hypothesis that progesterone supports embryonic development by altering the
      maternal uterine environment.

PMID- 24115320
TI  - Controlled alignment of filamentous supramolecular assemblies of biomolecules
      into centimeter-scale highly ordered patterns by using nature-inspired magnetic
      guidance.

PMID- 24115322
TI  - Glucosylceramide mimics: highly potent GCase inhibitors and selective
      pharmacological chaperones for mutations associated with types 1 and 2 Gaucher
      disease.
AB  - A series of iminoxylitol derivatives carrying a C-linked di-O-acyl or di-O-alkyl
      glyceryl substituent were prepared and characterized. All of these compounds,
      which were designed as glucosylceramide (GlcCer) mimics, were nanomolar
      inhibitors of lysosomal beta-glucosidase (glucocerebrosidase, GCase). Two of
      these pseudoglycolipids were further evaluated for their ability to enhance the
      activity of mutant GCase in human Gaucher cells. Although the di-O-hexyl ether
      was surprisingly devoid of chaperoning activity on both N370S and L444P GCases,
      the di-O-decanoyl ester was a potent chaperone of the L444P hydrolase, capable of
      increasing the residual activity of the enzyme by a factor of two at a very low
      concentration (50 nM); such a significant effect on the L444P mutation in human
      fibroblasts has not yet been observed. In heat-stress studies, the diether was
      found to be much more effective in stabilizing the wild-type enzyme than the
      diester. Four representative pseudoglycolipids were also assayed as inhibitors of
      GlcCer synthase, because such compounds could find use in the substrate reduction
      therapy approach to treat lysosomal storage diseases, but these compounds
      revealed only moderate activity. As efficient pharmacological chaperones, new
      structures such as the di-C10 -ester constitute leads for the development of
      therapeutic agents for types 2 and 3 Gaucher disease, the most severe
      neuronopathic forms of this lysosomal disease. 

PMID- 24115323
TI  - Enantio- and diastereoconvergent cyclocondensation reactions: synthesis of
      enantiopure cis-decahydroquinolines.
AB  - Up to four stereocenters with a well-defined configuration are generated in a
      single synthetic step by the cyclocondensation of (R)-phenylglycinol or (1S,2R)-1
      amino-2-indanol with stereoisomeric mixtures (racemates, meso forms,
      diastereoisomers) of cyclohexanone-based delta-keto-acid and delta-keto-diacid
      derivatives in enantio- and diastereoconvergent processes that involve dynamic
      kinetic resolution and/or desymmetrization of enantiotopic groups. A detailed
      analysis of the stereochemical outcome of this process is presented. This method
      provides easy access to enantiopure 8- and 6,8-substituted cis
      decahydroquinolines, including alkaloids of the myrioxazine family. 

PMID- 24115324
TI  - Selective imaging of the angiogenic relevant integrins alpha5beta1 and
      alphavbeta3.
AB  - Pattern seekers: For the two angiogenic relevant integrins alpha5beta1 and
      alphavbeta3, functionalized derivatives of the selective antagonists 1 and 2
      could target and discriminate between tumor cells in vivo based on their
      different integrin patterns and also delay tumor growth in vivo. In addition, the
      first alpha5beta1-selective integrin antagonist that enables specific molecular
      imaging by positron emission tomography was developed. 

PMID- 24115326
TI  - 25th anniversary article: no assembly required: recent advances in fully
      conjugated block copolymers.
AB  - Fully conjugated block copolymers have emerged as promising materials that
      combine semiconducting properties with the ability to self-assemble at the
      nanoscale. The convergence of these two features has tremendous implications for
      a number of fundamental molecular assembly and transport questions, while also
      offering unique advantages for a variety of applications. For example, a
      nanostructured active layer in organic photovoltaic (OPV) devices may provide for
      efficient charge separation while simultaneously affording continuous, unimpeded
      pathways for charge carriers to migrate to their respective electrodes within
      each individual microphase. This review details the recent progress made in the
      preparation and application of fully conjugated block copolymers and serves as a
      comprehensive reference for the materials that have been reported in the
      literature to date. Focus is placed on fully conjugated block copolymers prepared
      using chemistries that are relevant to high-performance polymers in organic
      electronics research, for example Stille, Suzuki-Miyaura, and Yamamoto coupling. 

PMID- 24115325
TI  - Palladium-catalyzed three-component diaryl sulfone synthesis exploiting the
      sulfur dioxide surrogate DABSO.

PMID- 24115327
TI  - Digital subtraction angiography in selection of the vascularized greater
      trochanter bone grafting for treatment of osteonecrosis of femoral head.
AB  - The aim of this report is to present our experience on the use of the digital
      subtraction angiography (DSA) in selection of the vascularized greater trochanter
      bone grafting for the treatment of the osteonecrosis of femoral head (ONFH) in
      early stages. Between January 2005 and June 2007, DSA was used to evaluate the
      blood perfusion of the early stages ONFH in 32 patients (45 hips). There were 18
      males and 14 females with an average age of 30 years old. Twenty-one hips were in
      ARCO stage I, and 24 in ARCO stage II. The arterial blood supply insufficiency
      was found in 22 hips by DSA, and the venous stasis in 23 hips. The hips with
      artery blood supply insufficiency received the vascularized greater trochanter
      bone grafting, and the hips with the venous stasis received the core
      decompression. All of patients were followed-up with an average of 4.8 years
      (ranging 2.4-6.6 years). The preoperative Harris Hip score (HHS) in the patients
      with arterial blood supply insufficiency was 48.18 +/- 7.81 and the postoperative
      HHS was 93.27 +/- 3.03. The preoperative HHS in the patients with venous stasis
      was 44.04 +/- 6.40, and the postoperative HHS 92.65 +/- .93. The postoperative
      DSA showed an improved perfusion of the femoral head in 44 hips. Our experience
      showed that DSA would help to select the appropriate procedure for treatment of
      ONFH in the early stage.

PMID- 24115329
TI  - Diagnosis of focal liver lesions with gadoxetic acid-enhanced MRI: is a shortened
      delay time possible by adding diffusion-weighted imaging?
AB  - PURPOSE: To determine whether the diagnostic performance of combined gadoxetic
      acid-enhanced dynamic phases and diffusion-weighted imaging (DWI) is comparable
      to the standard protocol with hepatobiliary phase (HBP) and DWI for detection and
      characterization of focal liver lesions in chronic liver disease. MATERIALS AND
      METHODS: A total of 176 patients with 181 HCCs, 15 cholangiocarcinomas, and 32
      benign lesions were included. Three combined gadoxetic acid-enhanced and DWI sets
      (dynamic phases [arterial, portal, and 3-min delay {3-min set} and dynamic phases
      with 10-min HBP [10-min set] or 20-min HBP [20-min set]) were analyzed by two
      observers to determine the diagnostic accuracy and sensitivity in detection of
      malignancy, and ability for lesion characterization. RESULTS: There was a trend,
      although not statistically significant, toward highest diagnostic accuracy and
      sensitivity for detecting malignancies in the 20-min set (mean, 0.945, 96.2),
      followed by the 10-min set (0.937, 95.9), and the 3-min set (0.923, 94.1) (P >
      0.05). For lesion characterization, three image sets were equivalent (P > 0.05).
      CONCLUSION: For lesion detection and characterization in chronic liver diseases,
      3-min set with DWI showed comparable efficacy to 10-min or 20-min set. However,
      the best diagnostic performance could be achieved by combination of all image
      sets.

PMID- 24115330
TI  - Toll-like receptors-2 and 4 are overexpressed in an experimental model of
      particle-induced osteolysis.
AB  - Aseptic loosening secondary to particle-associated periprosthetic osteolysis
      remains a major cause of failure of total joint replacements (TJR) in the mid-
      and long term. As sentinels of the innate immune system, macrophages are central
      to the recognition and initiation of the inflammatory cascade, which results in
      the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are
      involved in the recognition of pathogen-associated molecular patterns and danger
      associated molecular patterns. Experimentally, polymethylmethacrylate and
      polyethylene (PE) particles have been shown to activate macrophages via the TLR
      pathway. The specific TLRs involved in PE particle-induced osteolysis remain
      largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a
      critical role in the development of PE wear particle-induced osteolysis in the
      murine calvarium model. To test this hypothesis, we first demonstrated that PE
      particles caused observable osteolysis, visible by microCT and bone
      histomorphometry when the particles were applied to the calvarium of C57BL/6
      mice. The number of TRAP positive osteoclasts was significantly greater in the PE
      treated group when compared to the control group without particles. Finally,
      using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle
      induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may
      represent novel therapeutic targets for prevention of wear particle-induced
      osteolysis and accompanying TJR failure.

PMID- 24115334
TI  - The cleavage domain of the amyloid precursor protein transmembrane helix does not
      exhibit above-average backbone dynamics.
AB  - Wobbly backbone: The backbone dynamics of the amyloid precursor protein (APP)
      transmembrane helix was compared to those of other transmembrane domains. In
      contrast to expectation, no above-average backbone dynamics was found for the APP
      transmembrane helix; the dynamics thus appears not to be optimized for cleavage. 

PMID- 24115331
TI  - Pax6 mediates beta-catenin signaling for self-renewal and neurogenesis by
      neocortical radial glial stem cells.
AB  - The Wnt/beta-catenin pathway is a critical stem cell regulator and plays
      important roles in neuroepithelial cells during early gestation. However, the
      role of Wnt/beta-catenin signaling in radial glia, a major neural stem cell
      population expanded by midgestation, remains poorly understood. This study shows
      that genetic ablation of beta-catenin with hGFAP-Cre mice inhibits neocortical
      formation by disrupting radial glial development. Reduced radial glia and
      intermediate progenitors are found in the beta-catenin-deficient neocortex during
      late gestation. Increased apoptosis and divergent localization of radial glia in
      the subventricular zone are also observed in the mutant neocortex. In vivo and in
      vitro proliferation and neurogenesis as well as oligodendrogenesis by cortical
      radial glia or by dissociated neural stem cells are significantly defective in
      the mutants. Neocortical layer patterning is not apparently altered, while
      astrogliogenesis is ectopically increased in the mutants. At the molecular level,
      the expression of the transcription factor Pax6 is dramatically diminished in the
      cortical radial glia and the sphere-forming neural stem cells of beta-catenin
      deficient mutants. Chromatin immunoprecipitation and luciferase assays
      demonstrate that beta-catenin/Tcf complex binds to Pax6 promoter and induces its
      transcriptional activities. The forced expression of Pax6 through lentiviral
      transduction partially rescues the defective proliferation and neurogenesis by
      beta-catenin-deficient neural stem cells. Thus, Pax6 is a novel downstream target
      of the Wnt/beta-catenin pathway, and beta-catenin/Pax6 signaling plays critical
      roles in self-renewal and neurogenesis of radial glia/neural stem cells during
      neocortical development.

PMID- 24115335
TI  - Effects of charge and charge distribution on the cellular uptake of multivalent
      arginine-containing peptide-polymer conjugates.
AB  - Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-methacryloyl-beta
      alaninyl-S-benzyl thioester were prepared by employing free radical or RAFT
      conditions and denominated as "NCL polymers". The copolymer with a polydispersity
      index of 1.2-1.3 was used for the direct conjugation of unprotected peptides and
      peptide mixtures bearing differentially loaded side chains by native chemical
      ligation reactions conducted in aqueous buffer. Uptake into human HeLa cells was
      correlated with the overall surface charge and the zeta potentials of the peptide
      polymer conjugates. Most notable were the differential effects found for various
      multivalent peptide-polymer conjugates containing arginine residues. Although
      positive zeta potentials were required for cellular uptake of the peptide-polymer
      conjugates, this sole charge effect was strongly dominated by the effect exerted
      by the relative distribution of arginine residues. Polymers conjugated with nona
      arginine peptides were over-proportionally taken up, relative to their surface
      charge, compared to polymers with random distribution of single arginine
      residues. In view of these findings, peptide-polymer compositions suitable for
      efficient cellular uptake with negligible toxicity at polymer concentrations
      relevant for intracellular functional studies were determined. 

PMID- 24115336
TI  - Higher temperature sensitivity for stable than for labile soil organic carbon-
      evidence from incubations of long-term bare fallow soils.
AB  - The impact of climate change on the stability of soil organic carbon (SOC)
      remains a major source of uncertainty in predicting future changes in atmospheric
      CO2 levels. One unsettled issue is whether the mineralization response to
      temperature depends on SOC mineralization rate. Long-term (>25 years) bare fallow
      experiments (LTBF) in which the soil is kept free of any vegetation and organic
      inputs, and their associated archives of soil samples represent a unique research
      platform to examine this issue as with increasing duration of fallow, the
      lability of remaining total SOC decreases. We retrieved soils from LTBF
      experiments situated at Askov (Denmark), Grignon (France), Ultuna (Sweden), and
      Versailles (France) and sampled at the start of the experiments and after 25, 50,
      52, and 79 years of bare fallow, respectively. Soils were incubated at 4, 12, 20,
      and 35  degrees C and the evolved CO2 monitored. The apparent activation energy
      (Ea) of SOC was then calculated for similar loss of CO2 at the different
      temperatures. The Ea was always higher for samples taken at the end of the bare
      fallow period, implying a higher temperature sensitivity of stable C than of
      labile C. Our results provide strong evidence for a general relationship between
      temperature sensitivity and SOC stability upon which significant improvements in
      predictive models could be based.

PMID- 24115337
TI  - Characterization of residual beta cell function in long-standing type 1 diabetes.
AB  - BACKGROUND: Some patients with long-standing type 1 diabetes (T1D) maintain
      detectable levels of C-peptide. The quantitative and qualitative aspects of
      insulin secretion in these subjects have not been assessed, but may shed light on
      the basis for maintained beta cell function. Our objective was to characterize
      insulin secretion in subjects with varying duration of T1D. METHODS: Data from
      mixed-meal tolerance tests were collected in this cross-sectional study. We
      screened 58 subjects with T1D <1 year and 34 subjects with T1D >2 years, 20 of
      whom had previously participated in trials of anti-CD3 monoclonal antibody. Data
      from 38 historical non-diabetic controls were utilized. Insulin secretory rates
      were calculated from C-peptide levels from mixed-meal tolerance tests. Patterns
      and rates of insulin secretion were characterized along with relationships
      between insulin secretion and clinical parameters. RESULTS: C-peptide was
      detected in 68% of subjects with T1D duration >2 years. Insulin secretion was
      negatively correlated with HgbA(1c) and insulin use. A decline in total insulin
      secretion was seen with increasing disease duration (p < 0.0001). More subjects
      with long duration of T1D had a delayed time to peak secretion compared with
      those with new onset T1D or non-diabetic subjects. Insulin and glucagon secretory
      responses appeared unrelated. CONCLUSIONS: Meal-stimulated insulin secretory
      responses are seen in those with long-standing T1D and detectable C-peptide.
      Delayed insulin secretory responses are more common in individuals with longer
      disease duration. Residual insulin secretory responses are associated with
      improved clinical parameters.

PMID- 24115338
TI  - Herpes simplex encephalitis relapse with chorea is associated with autoantibodies
      to N-Methyl-D-aspartate receptor or dopamine-2 receptor.
AB  - BACKGROUND: Movement disorder relapses after herpes simplex virus 1 (HSV1)
      encephalitis have been hypothesized to be secondary to postviral autoimmunity.
      Recently, a proportion of patients with HSV1 encephalitis (HSE) were shown to
      produce autoantibodies against N-methyl-D-aspartate receptor (NMDAR). METHODS: We
      measured autoantibodies against NMDAR and dopamine-2 receptor (D2R) expressed at
      the cell surface in the stored acute serum of 9 children with HSE, 3 of whom had
      a relapsing course with chorea. RESULTS: The 3 patients with chorea had elevated
      autoantibodies against NMDAR (n = 1), D2R (n = 1), or both (n = 1), whereas
      patients without chorea were negative (n = 6). The prospectively identified
      patient with chorea and NMDAR autoantibodies improved after early treatment with
      steroids, intravenous immunoglobulin, and cyclophosphamide, with reduction in
      serum NMDAR antibody titers. CONCLUSIONS: These autoantibody findings lend
      support to the autoimmune hypothesis and the early use of immune suppression in
      post-HSE chorea.

PMID- 24115339
TI  - Two-step OFFGEL approach for effective peptide separation compatible with iTRAQ
      labeling.
AB  - Shotgun proteomic analyses are increasingly becoming methods of choice for
      complex samples. The development of effective methods for fractionating peptides
      to reduce the complexity of the sample before mass analysis is a key point in
      this strategy. The OFFGEL technology has recently become a tool of choice in
      proteomic analysis at peptide level. This OFFGEL electrophoresis (OGE) approach
      allows the in-solution separation of peptides from various biological sources by
      isoelectric focusing in highly resolved 24 fractions. It was also demonstrated
      that OGE technology is a filtering tool for pI-based validation of peptide
      identification. As peptide OGE is compatible with iTRAQ labeling, OGE is finding
      valuable applications in quantitative proteomics as well. The aim of this study
      is to explain a new 2D-OGE approach that improves the proteomic coverage of
      complex mixtures such as colorectal cell line lysates, and which is compatible
      with iTRAQ labeling. 

PMID- 24115340
TI  - Does use of tetracyclic antidepressant-mirtazapine reduce cancer risk in
      depression patients?
AB  - PURPOSE: We conducted a nested case-control study to evaluate the association
      between risk of cancer and mirtazapine use in depression patients in Taiwan.
      METHODS: We obtained data from the Taiwan National Health Insurance Research
      Database to conduct a population-based nested case-control study. The study
      cohort included 16 897 patients diagnosed with depression between January 1, 2000
      and December 31, 2008. We identified 530 cancer patients as the study group and
      matched 4 non-cancer subjects with each cancer patient by incident density, age,
      and sex. Odds ratios and 95% confidence intervals were estimated using
      multivariate conditional logistic regression analysis. RESULTS: Use of
      mirtazapine for depression did not have significant effect on overall cancer
      incidence (odds ratio: 1.03, 95% confidence interval: 0.72-1.48). Further
      analysis of annual mirtazapine dosages and the duration of mirtazapine use
      revealed no significant effect on cancer risk. CONCLUSION: The findings of this
      population-based nested case-control study suggest that mirtazapine use may not
      provide a tumor suppression effect in humans such as that seen in the animal
      model. Future large-scale and in-depth investigations in this area are warranted.

PMID- 24115341
TI  - Structural characterization of alpha/beta-peptides having alternating residues: X
      ray structures of the 11/9-helix from crystals of racemic mixtures.

PMID- 24115343
TI  - Psychopathology and cognition in children with 22q11.2 deletion syndrome.
AB  - BACKGROUND: Children with 22q11.2 deletion syndrome (22q11.2DS) have been
      reported to have high rates of cognitive and psychiatric problems. AIMS: To
      establish the nature and prevalence of psychiatric disorder and neurocognitive
      impairment in children with 22q11.2DS and test whether risk of psychopathology is
      mediated by the children's intellectual impairment. METHOD: Neurocognition and
      psychopathology were assessed in 80 children with 22q11.2DS (mean age 10.2 years,
      s.d. = 2.1) and 39 sibling controls (mean age 10.9 years, s.d. = 2.0). RESULTS:
      More than half (54%) of children with 22q11.2DS met diagnostic criteria for one
      or more DSM-IV-TR psychiatric disorder. These children had lower IQ (mean 76.8,
      s.d. = 13.0) than controls (mean 108.6, s.d. = 15.2) (P<0.001) and showed a range
      of neurocognitive impairments. Increased risk of psychopathology was not mediated
      by intellectual impairment. CONCLUSIONS: 22q11.2DS is not related to a specific
      psychiatric phenotype in children. Moreover, the deletion has largely independent
      effects on IQ and risk of psychopathology, indicating that psychopathology in
      22q11.2DS is not a non-specific consequence of generalised cognitive impairment.

PMID- 24115344
TI  - Post-traumatic stress reactions in survivors of the 2011 massacre on Utoya
      Island, Norway.
AB  - BACKGROUND: Although youths in many countries have been exposed to terrorism, few
      studies have examined early risk and protective factors for the subsequent
      development of mental health problems. AIMS: To investigate the levels of post
      traumatic stress in survivors of the 2011 massacre on Utoya Island compared with
      the general population in Norway, and to identify predictive factors. METHOD:
      Four hundred and ninety survivors were invited to participate. Structured face-to
      face interviews were performed 4-5 months after the attack. RESULTS: There were
      325 study participants (response rate 66%). Survivors had been highly exposed to
      danger and loss. Post-traumatic stress levels were more than six times higher in
      survivors than in the general population. Predictors were female gender, minority
      ethnic status, high level of trauma exposure, pain, the loss of someone close and
      social support. CONCLUSIONS: Survivor characteristics that can be assessed in the
      early aftermath of a terrorist attack strongly predict the subsequent mental
      health problems of exposed youths. The highly elevated symptoms observed were
      largely attributable to the traumatic experience and reflect the mental health
      costs of the terrorist attack.

PMID- 24115342
TI  - Dietary patterns and suicide in Japanese adults: the Japan Public Health Center
      based Prospective Study.
AB  - BACKGROUND: Although dietary patterns have been linked to depression, a
      frequently observed precondition for suicide, no study has yet examined the
      association between dietary patterns and suicide risk. AIMS: To prospectively
      investigate the association between dietary patterns and death from suicide.
      METHOD: Participants were 40 752 men and 48 285 women who took part in the second
      survey of the Japan Public Health Center-based Prospective Study (1995-1998).
      Dietary patterns were derived from principal component analysis of the
      consumption of 134 food and beverage items ascertained by a food frequency
      questionnaire. Hazard ratios of suicide from the fourth year of follow-up to
      December 2005 were calculated. RESULTS: Among both men and women, a 'prudent'
      dietary pattern characterised by a high intake of vegetables, fruits, potatoes,
      soy products, mushrooms, seaweed and fish was associated with a decreased risk of
      suicide. The multivariable-adjusted hazard ratio of suicide for the highest v.
      lowest quartiles of the dietary pattern score was 0.46 (95% CI 0.28-0.75) (P for
      trend, 0.005). Other dietary patterns (Westernised and traditional Japanese) were
      not associated with suicide risk. CONCLUSIONS: Our findings suggest that a
      prudent dietary pattern may be associated with a decreased risk of death from
      suicide.

PMID- 24115345
TI  - Feasibility, acceptability and efficacy of a school-based prevention programme
      for eating disorders: cluster randomised controlled trial.
AB  - BACKGROUND: Body image dissatisfaction during adolescence is common but not
      benign. School-based interventions have the potential for wide reach, but
      scalability of previous programmes is limited by a reliance on external
      facilitators. AIMS: To assess the acceptability, feasibility and efficacy of a
      teacher-delivered body image intervention. METHOD: A pilot clustered randomised
      controlled trial in which 16 classes of adolescent girls were allocated to a 6
      session body image programme (n = 261), or usual curriculum control (n = 187)
      (registration: ISRCTN42594993). RESULTS: Students in the intervention group had
      significantly improved body esteem and self-esteem and reduced thin-ideal
      internalisation. Effects for body esteem and thin-ideal internalisation were
      maintained for 3 months. There were no group differences for eating pathology,
      peer factors or depression. Acceptability, feasibility and efficacy varied
      between schools. CONCLUSIONS: Teacher-delivered body image lessons have promise
      but further work is needed to increase efficacy and make interventions suitable
      across a range of schools.

PMID- 24115346
TI  - Prospective prediction of suicide in a nationally representative sample:
      religious service attendance as a protective factor.
AB  - BACKGROUND: Previous research into religious service attendance as a protective
      factor against suicide has been conducted only retrospectively, with
      psychological autopsy studies using proxy informants of completed suicide, rather
      than prospectively, with completed suicide as a dependent variable. AIMS: To
      determine whether individuals who frequently attended religious services were
      less likely to die by suicide than those who did not attend so frequently.
      METHOD: We analysed data from a nationally representative sample (n = 20 014),
      collected in the USA between 1988 and 1994, and follow-up mortality data from
      baseline to the end of 2006. RESULTS: Cox proportional hazard regression analysis
      indicated that those who frequently attended religious services were less likely
      to die by suicide than those who did not attend, after accounting for the effects
      of other relevant risk factors. CONCLUSIONS: Frequent religious service
      attendance is a long-term protective factor against suicide.

PMID- 24115347
TI  - Prenatal maternal depression symptoms and nutrition, and child cognitive
      function.
AB  - BACKGROUND: Little is currently known about how maternal depression symptoms and
      unhealthy nutrition during pregnancy may developmentally interrelate to
      negatively affect child cognitive function. AIMS: To test whether prenatal
      maternal depression symptoms predict poor prenatal nutrition, and whether this in
      turn prospectively associates with reduced postnatal child cognitive function.
      METHOD: In 6979 mother-offspring pairs participating in the Avon Longitudinal
      Study of Parents and Children (ALSPAC) in the UK, maternal depression symptoms
      were assessed five times between 18 weeks gestation and 33 months old. Maternal
      reports of the nutritional environment were assessed at 32 weeks gestation and 47
      months old, and child cognitive function was assessed at age 8 years. RESULTS:
      During gestation, higher depressive symptoms were related to lower levels of
      healthy nutrition and higher levels of unhealthy nutrition, each of which in turn
      was prospectively associated with reduced cognitive function. These results were
      robust to postnatal depression symptoms and nutrition, as well as a range of
      potential prenatal and postnatal confounds (i.e. poverty, teenage mother, low
      maternal education, parity, birth complications, substance use, criminal
      lifestyle, partner cruelty towards mother). CONCLUSIONS: Prenatal interventions
      aimed at the well-being of children of parents with depression should consider
      targeting the nutritional environment.

PMID- 24115348
TI  - Flow cytometric quantification of intraperitoneal free tumor cells in patients
      with peritoneal metastasis.
AB  - BACKGROUND: Peritoneal metastasis (PM) is the most life-threatening type of
      metastasis in abdominal malignancy. To improve the diagnostic accuracy of
      cytologic detection (CY) of free tumor cells (FTC) in the peritoneal cavity, we
      tried to quantify the FTC to leukocyte ratio using flow cytometry in patients
      with peritoneal metastasis. METHODS: Cells were recovered from ascites or
      peritoneal lavages from 106 patients who underwent abdominal surgery and
      additional 89 samples which were obtained from peritoneal catheter or access port
      in patients with PM (+) gastric cancer. The cells were immunostained with
      monoclonal antibodies to CD45 and to CD326 (EpCAM). Using flow cytometry, CD326
      (+) and CD45 (+) cells were classified as either tumor cells (T) or leukocytes
      (L) and the T/L ratio (TLR) was calculated. RESULTS: In 106 samples obtained by
      laparotomy, Median (M) of the TLR of PM (+) patients was 1.39% (0-807.87%) which
      was significantly higher than PM (-) patients (M=0%, 0-2.14%, P < 0.001). In PM
      (+) patients, 86 CY (+) samples showed higher TLR than 61 CY (-) samples
      (M=2.81%, 0.02-1868.44% vs. M=0%, 0-3.45%, p<0.0001). In all of the 24 patients
      who were monitored for TLR before and after intraperitoneal (IP) chemotherapy,
      the TLR was reduced which was more dramatic than the results of the change in
      cytology. CONCLUSIONS: TLR measured with FACS is an excellent reflection of the
      tumor spread in the peritoneal cavity and could be a reliable diagnostic
      biomarker to determine the severity of PM as well as effectiveness of IP
      chemotherapy.

PMID- 24115349
TI  - DFT study on the recovery of Hoveyda-grubbs-type catalyst precursors in enyne and
      diene ring-closing metathesis.
AB  - DFT (B3LYP-D) calculations have been used to better understand the origin of the
      recovered Hoveyda-Grubbs derivative catalysts after ring-closing diene or enyne
      metathesis reactions. For that, we have considered the activation process of five
      different Hoveyda-Grubbs precursors in the reaction with models of usual diene
      and enyne reactants as well as the potential precursor regeneration through the
      release/return mechanism. The results show that, regardless of the nature of the
      initial precursor, the activation process needs to overcome relatively high
      energy barriers, which is in agreement with a relatively slow process. The
      precursor regeneration process is in all cases exergonic and it presents low
      energy barriers, particularly when compared to those of the activation process.
      This indicates that the precursor regeneration should always be feasible, unlike
      the moderate recoveries sometimes observed experimentally, which suggests that
      other competitive processes that hinder recovery should take place. Indeed,
      calculations presented in this work show that the reactions between the more
      abundant olefinic products and the active carbenes usually require lower energy
      barriers than those that regenerate the initial precatalyst, which could prevent
      precursor regeneration. On the other hand, varying the precursor concentration
      with time obtained from the computed energy barriers shows that, under the
      reaction conditions, the precursor activation is incomplete, thereby suggesting
      that the origin of the recovered catalyst probably arises from incomplete
      precursor activation. 

PMID- 24115350
TI  - Solvent- and catalyst-free huisgen cycloaddition to rufinamide in flow with a
      greener, less expensive dipolarophile.
AB  - Give it a flow: A continuous-flow process for the synthesis of a 1,2,3-triazole
      precursor of Rufinamide has been developed. The protocol involves a solvent- and
      catalyst-free operation and utilizes reaction temperatures above the melting
      point of the target product to prevent microreactor clogging, resulting in a
      decrease of the operating time from hours to minutes. 

PMID- 24115351
TI  - Equilibrium of contact and solvent-separated ion pairs in mixtures of protic
      ionic liquids and molecular solvents controlled by polarity.
AB  - Polarity controls the equilibrium constants and free energies of contact ion
      pairs (CIPs) and solvent-separated ion pairs (SIPs) in mixtures of protic ionic
      liquids and molecular solvents. The subtle balance between the ionic species was
      studied by far-infrared difference spectra and related DFT-calculated properties
      for solvents of low and high polarity and for different solvent concentrations. 

PMID- 24115352
TI  - Mitochondrial DNA rearrangements in health and disease--a comprehensive study.
AB  - Mitochondrial DNA (mtDNA) rearrangements cause a wide variety of highly
      debilitating and often fatal disorders and have been implicated in aging and age
      associated disease. Here, we present a meta-analytical study of mtDNA deletions
      (n = 730) and partial duplications (n = 37) using information from more than 300
      studies published over the last 30 years. We show that both classes of mtDNA
      rearrangements are unequally distributed among disorders and their breakpoints
      have different genomic locations. We also demonstrate that 100% of cases with
      sporadic mtDNA deletions and 97.3% with duplications have no breakpoints in the
      16,071 breakage hotspot site, in contrast with deletions from healthy and aged
      tissues. Notably, most deletions removing a section of the D-loop are found in
      tumors. Deleted mtDNA molecules lacking the origin of L-strand replication (O(L))
      represent only 9.5% of all reported cases, whereas extra origins of replication
      occur in all duplications. As previously shown for deletions, imperfect stretches
      of homology are common in duplication breakpoints. Finally, we provide a
      dedicated Website with detailed information on deleted/duplicated mtDNA regions
      to facilitate the design of efficient methods for identification and screening of
      rearranged mitochondrial genomes (available at
      http://www.portugene.com/mtDNArearrangements.html).

PMID- 24115353
TI  - Multilayered Si nanoparticle/reduced graphene oxide hybrid as a high-performance
      lithium-ion battery anode.
AB  - Multilayered Si/RGO anode nanostructures, featuring alternating Si nanoparticle
      (NP) and RGO layers, good mechanical stability, and high electrical conductivity,
      allow Si NPs to easily expand between RGO layers, thereby leading to high
      reversible capacity up to 2300 mAh g(-1) at 0.05 C (120 mA g(-1) ) and 87%
      capacity retention (up to 630 mAh g(-1) ) at 10 C after 152 cycles. 

PMID- 24115354
TI  - Cloning, expression patterns, and preliminary characterization of AccCPR24, a
      novel RR-1 type cuticle protein gene from Apis cerana cerana.
AB  - Cuticular proteins (CPs) are key components of insect cuticle, a structure that
      plays a pivotal role in insect development and defense. In this study, we cloned
      the full-length cDNA of a CP gene from Apis cerana cerana (AccCPR24). An amino
      acid sequence alignment indicated that AccCPR24 contains the conserved Rebers and
      Riddiford consensus sequence and shares high similarity with the genes from other
      hymenopteran insects. We then isolated the genomic DNA and found that the first
      intron, which is present in other CP genes, is absent in AccCPR24. Real-time
      quantitative polymerase chain reaction (qPCR) analysis revealed that AccCPR24 is
      highly expressed in the late pupal stage and midgut. Expression was inhibited by
      an exogenous ecdysteroid in vitro but was enhanced by this hormone in vivo;
      environmental stressors, such as heavy metals and pesticides, also influenced
      gene expression. In addition, a disc diffusion assay showed that AccCPR24
      enhanced the ability of bacterial cells to resist multiple stresses. We infer
      from our results that AccCPR24 acts in honeybee development and in protecting
      these insects from abiotic stresses. 

PMID- 24115355
TI  - End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis,
      purification, and final dosage formation.
AB  - A series of tubes: The continuous manufacture of a finished drug product starting
      from chemical intermediates is reported. The continuous pilot-scale plant used a
      novel route that incorporated many advantages of continuous-flow processes to
      produce active pharmaceutical ingredients and the drug product in one integrated
      system. 

PMID- 24115356
TI  - Probing binding and cellular activity of pyrrolidinone and piperidinone small
      molecules targeting the urokinase receptor.
AB  - The urokinase receptor (uPAR) is a cell-surface protein that is part of an
      intricate web of transient and tight protein interactions that promote cancer
      cell invasion and metastasis. Here, we evaluate the binding and biological
      activity of a new class of pyrrolidinone and piperidinone compounds, along with
      derivatives of previously-identified pyrazole and propylamine compounds.
      Competition assays revealed that the compounds displace a fluorescently labeled
      peptide (AE147-FAM) with inhibition constant (Ki ) values ranging from 6 to 63
      MUM. Structure-based computational pharmacophore analysis followed by extensive
      explicit-solvent molecular dynamics (MD) simulations and free energy calculations
      suggested the pyrazole-based and piperidinone-based compounds adopt different
      binding modes, despite their similar two-dimensional structures. In cells,
      pyrazole-based compounds showed significant inhibition of breast adenocarcinoma
      (MDA-MB-231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but
      piperidinone-containing compounds exhibited no cytotoxicity even at
      concentrations of 100 MUM. One pyrazole-based compound impaired MDA-MB-231
      invasion, adhesion, and migration in a concentration-dependent manner, while the
      piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix
      metalloprotease-9 (gelatinase) activity in a concentration-dependent manner,
      while the piperidinone showed no effect suggesting different mechanisms for
      inhibition of cell invasion. Signaling studies further highlighted these
      differences, showing that pyrazole compounds completely inhibited ERK
      phosphorylation and impaired HIF1alpha and NF-kappaB signaling, while
      pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that
      the effect of the pyrazole-based compound on proliferation was due to cell
      killing through an apoptotic mechanism. The compounds identified represent
      valuable leads in the design of further derivatives with higher affinities and
      potential probes to unravel the protein-protein interactions of uPAR. 

PMID- 24115357
TI  - Brief report: astrogliosis promotes functional recovery of completely transected
      spinal cord following transplantation of hESC-derived oligodendrocyte and
      motoneuron progenitors.
AB  - Spinal cord injury results in neural loss and consequently motor and sensory
      impairment below the injury. Reactive astrocytes contribute to formation of glial
      scar, thus impeding axonal regeneration, through secretion of extracellular
      matrix molecules, chondroitin sulfate proteoglycans (CSPGs). In this study, we
      analyze lesion site tissue to reveal the possible mechanism underlying the
      functional recovery after cell transplantation of human embryonic stem cell
      (hESC)-derived oligodendrocyte progenitor cell (OPC) and motoneuron progenitors
      (MP) and propose that transplanted cells increase astrogliosis through the
      regenerative signaling pathways activated in the host tissue that may crucial for
      restoring locomotor ability. We show that the transplantation of hESC-derived OPC
      and MP promotes astrogliosis, through activation of Jagged1-dependent Notch and
      Jak/STAT signaling that support axonal survival. The transplanted cells in
      synergism with reactive astrocytes create permissive environment in which the
      expression of detrimental genes (Cspg, Tenascins, and genes involved in SLIT/ROBO
      signaling) was significantly decreased while expression of beneficial ones
      (Laminins and Fibronectin) was increased. According to our data, this mechanism
      is activated in all transplantation groups independently of the level of
      locomotor recovery. These results indicate that modifying the beneficial function
      of reactive astrocytes could be a feasible therapeutic strategy for spinal cord
      injury in future.

PMID- 24115358
TI  - Re: High- and low-fat dairy intake, recurrence, and mortality after breast cancer
      diagnosis.

PMID- 24115359
TI  - Re: High- and low-fat dairy intake, recurrence, and mortality after breast cancer
      diagnosis. Response.

PMID- 24115360
TI  - Functional role of CLIC1 ion channel in glioblastoma-derived stem/progenitor
      cells.
AB  - BACKGROUND: Chloride channels are physiologically involved in cell division and
      motility. Chloride intracellular channel 1 (CLIC1) is overexpressed in a variety
      of human solid tumors compared with normal tissues, suggesting a potential
      involvement of CLIC1 in the regulation of tumorigenesis. This led us to
      investigate the role of CLIC1 in gliomagenesis. METHODS: We used the neurosphere
      system to isolate stem/progenitor cells from human glioblastomas (GBMs). CLIC1
      targeting in GBM neurospheres was achieved by both lentiviral-mediated short
      hairpin RNA transduction and CLIC1 antibody treatment, and its effect on stem
      like properties was analyzed in vitro by proliferation and clonogenic assays and
      in vivo by orthotopic injection in immunocompromised mice. Channel activity was
      studied by perforated patch clamp technique. Differences in expression were
      analyzed by analysis of variance with Tamhane's multiple comparison test. Kaplan
      Meier analyses and log-rank test were used to assess survival. All statistical
      tests were two-sided. RESULTS: CLIC1 was statistically significantly
      overexpressed in GBMs compared with normal brain tissues (P < .001) with a better
      survival of patients with CLIC1 low-expressing tumors (CLIC1(low) vs CLIC1(high)
      survival: chi(2) = 74.35; degrees of freedom = 1; log-rank P < .001). CLIC1 was
      variably expressed in patient-derived GBM neurospheres and was found enriched in
      the stem/progenitor compartment. CLIC1 silencing reduced proliferative (P < .01),
      clonogenic (P < .01), and tumorigenic capacity (P < .05) of stem/progenitor
      cells. The reduction of CLIC1 chloride currents with a specific CLIC1 antibody
      mirrored the biological effects of CLIC1 silencing in GBM patient-derived
      neurospheres. CONCLUSIONS: Reduced gliomagenesis after CLIC1 targeting in tumoral
      stem/progenitor cells and the finding that CLIC1 expression is inversely
      associated with patient survival suggest CLIC1 as a potential target and
      prognostic biomarker.

PMID- 24115361
TI  - The prostate, lung, colorectal, and ovarian cancer screening trial and its
      associated research resource.
AB  - The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a
      large-scale research effort conducted by the National Cancer Institute. PLCO
      offers an example of coordinated research by both the extramural and intramural
      communities of the National Institutes of Health. The purpose of this article is
      to describe the PLCO research resource and how it is managed and to assess the
      productivity and the costs associated with this resource. Such an in-depth
      analysis of a single large-scale project can shed light on questions such as how
      large-scale projects should be managed, what metrics should be used to assess
      productivity, and how costs can be compared with productivity metrics. A
      comprehensive publication analysis identified 335 primary research publications
      resulting from research using PLCO data and biospecimens from 2000 to 2012. By
      the end of 2012, a total of 9679 citations (excluding self-citations) have
      resulted from this body of research publications, with an average of 29.7
      citations per article, and an h index of 45, which is comparable with other large
      scale studies, such as the Nurses' Health Study. In terms of impact on public
      health, PLCO trial results have been used by the US Preventive Services Task
      Force in making recommendations concerning prostate and ovarian cancer screening.
      The overall cost of PLCO was $454 million over 20 years, adjusted to 2011
      dollars, with approximately $37 million for the collection, processing, and
      storage of biospecimens, including blood samples, buccal cells, and pathology
      tissues.

PMID- 24115362
TI  - Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography
      pancreatitis after liver transplantation: a retrospective analysis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for
      diagnosis and therapeutic interventions in recipients of liver transplantation
      (LT) who develop biliary complications. Post-endoscopic retrograde
      cholangiopancreatography acute pancreatitis (PEP) is the most common major
      adverse event after ERCP; however, the frequency of PEP in LT recipients is not
      well established. We aimed to determine the rate of PEP in this population and to
      identify its predictors, especially among immunosuppressive agents. We reviewed
      all ERCP procedures performed in LT recipients after duct-to-duct biliary
      anastomoses at 2 high-volume transplant centers. Patients who had undergone
      sphincterotomy or had a surgically altered pancreaticobiliary anatomy before LT
      were excluded. Electronic medical records and endoscopy databases were used to
      obtain clinical, endoscopic, and medication data. A multivariate logistic
      regression analysis was used to determine predictors of PEP in this cohort. In
      all, 730 ERCP procedures were performed in 301 patients during the study period
      with an observed PEP rate of 3% (22/730). A univariate analysis revealed an
      increased risk of PEP with index ERCP after LT [odds ratio (OR) = 4.04, 95%
      confidence interval (CI) = 1.40-11.65] and in cases with difficult biliary
      cannulation (OR = 2.89, 95% CI = 1.10-7.65), whereas prednisone use was found to
      have a protective effect in both univariate (OR = 0.34, 95% CI = 0.14-0.84) and
      multivariate analyses (OR = 0.22, 95% CI = 0.09-0.57) after adjustments for
      difficult biliary cannulation and post-LT index ERCP. This retrospective analysis
      demonstrates that corticosteroid therapy has a protective role in the development
      of PEP in LT recipients. Further studies are warranted to confirm our findings.

PMID- 24115363
TI  - Square-micrometer-sized, free-standing organometallic sheets and their square
      centimeter-sized multilayers on solid substrates.
AB  - Oligofunctional terpyridine-based monomers are spread at an air/water interface,
      where they are connected with transition metal salts such as Fe(II) into
      mechanically coherent monolayer sheets of macroscopic dimension. The conversions
      of these processes are determined by XPS for several monomer/metal ion
      combinations. The sheets are transferred onto TEM grids, the 20 * 20 square
      micrometer sized holes of which can be spanned. AFM indentation experiments
      provide in-plane elastic moduli which are compared with naturally occurring
      sheets such as graphene. The new organometallic sheets are also used to create
      multilayer assemblies on square centimeter length scales on solid substrates.
      Finally some directions are provided where this research can lead to in future
      and where its application potential lies. 

PMID- 24115364
TI  - Plant population differentiation and climate change: responses of grassland
      species along an elevational gradient.
AB  - Mountain ecosystems are particularly susceptible to climate change.
      Characterizing intraspecific variation of alpine plants along elevational
      gradients is crucial for estimating their vulnerability to predicted changes.
      Environmental conditions vary with elevation, which might influence plastic
      responses and affect selection pressures that lead to local adaptation. Thus,
      local adaptation and phenotypic plasticity among low and high elevation plant
      populations in response to climate, soil and other factors associated with
      elevational gradients might underlie different responses of these populations to
      climate warming. Using a transplant experiment along an elevational gradient, we
      investigated reproductive phenology, growth and reproduction of the nutrient-poor
      grassland species Ranunculus bulbosus, Trifolium montanum and Briza media. Seeds
      were collected from low and high elevation source populations across the Swiss
      Alps and grown in nine common gardens at three different elevations with two
      different soil depths. Despite genetic differentiation in some traits, the
      results revealed no indication of local adaptation to the elevation of population
      origin. Reproductive phenology was advanced at lower elevation in low and high
      elevation populations of all three species. Growth and reproduction of T.
      montanum and B. media were hardly affected by garden elevation and soil depth. In
      R. bulbosus, however, growth decreased and reproductive investment increased at
      higher elevation. Furthermore, soil depth influenced growth and reproduction of
      low elevation R. bulbosus populations. We found no evidence for local adaptation
      to elevation of origin and hardly any differences in the responses of low and
      high elevation populations. However, the consistent advanced reproductive
      phenology observed in all three species shows that they have the potential to
      plastically respond to environmental variation. We conclude that populations
      might not be forced to migrate to higher elevations as a consequence of climate
      warming, as plasticity will buffer the detrimental effects of climate change in
      the three investigated nutrient-poor grassland species. 

PMID- 24115365
TI  - Base-pairing behavior of a carbocyclic Janus-AT nucleoside analogue capable of
      recognizing A and T within a DNA duplex.
AB  - Janus-type nucleosides are heterocycles with two faces, each of which is designed
      to complement the H-bonding interactions of natural nucleosides comprising a
      canonical Watson-Crick base pair. By intercepting all of the hydrogen bonds
      contained within the base pair, oligomeric Janus nucleosides are expected to
      achieve sequence-specific DNA recognition through the formation of J-loops that
      will be more stable than D-loops, which simply replaces one base-pair with
      another. Herein, we report the synthesis of a novel Janus-AT nucleoside analogue,
      JAT , affixed on a carbocyclic analogue of deoxyribose that was converted to the
      corresponding phosphoramidite. A single JAT was successfully incorporated into a
      DNA strand by solid phase for targeting both A and T bases, and characterized
      through biophysical and computational methods. Experimental UV-melting and
      circular dichroism data demonstrated that within the context of a standard
      duplex, JAT associates preferentially with T over A, and much more poorly with C
      and G. Density functional theory calculations confirm that the JAT structure is
      well suited to associate only with A and T thereby highlighting the importance of
      the electronic structure in terms of H-bonding. Finally, molecular dynamics
      simulations validated the observation that JAT can substitute more effectively as
      an A-analogue than as a T-analogue without substantial distortion of the B-helix.
      Overall, this new Janus nucleotide is a promising tool for the targeting of A-T
      base pairs in DNA, and will lead to the development of oligo-Janus-nucleotide
      strands for sequence-specific DNA recognition. 

PMID- 24115366
TI  - A novel peptide-modified and gene-activated biomimetic bone matrix accelerating
      bone regeneration.
AB  - The osteogenic differentiation of bone marrow stromal cells (BMSCs) can be
      regulated by systemic or local growth factor, especially by transforming growth
      factor beta 1 (TGF-beta1). However, how to maintain the bioactivity of exogenous
      TGF-beta1 is a great challenge due to its short half-life time. The most
      promising solution is to transfer TGF-beta1 gene into seed cells through
      transgenic technology and then transgenic cells to continuously secret endogenous
      TGF-beta1 protein via gene expression. In this study, a novel non-viral vector
      (K)16GRGDSPC was chemically linked to bioactive bone matrices PLGA-[ASP-PEG]n
      using cross-linker to construct a novel non-viral gene transfer system. TGF-beta1
      gene was incubated with this system and subsequently rabbit-derived BMSCs were co
      cultured with this gene-activated PLGA-[ASP-PEG]n, while co-cultured with PLGA
      [ASP-PEG]n modified with (K)16GRGDSPC only and original PLGA-[ASP-PEG]n as
      control. Thus we fabricated three kinds of composites: Group A (BMSCs-TGF
      beta1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); Group B (BMSCs-(K)16GRGDSPC
      PLGA-[ASP-PEG]n composite); and Group C (BMSCs-PLGA-[ASP-PEG]n composite). TGF
      beta1 and other osteogenic phenotype markers of alkaline phosphatase,
      osteocalcin, osteopontin and type I collagen in Group A were all significantly
      higher than the other two groups ex vivo. In vivo, 15-mm long segmental rabbit
      bone defects were created and randomly implanted the aforementioned composites
      separately, and then fixed with plate-screws. The results demonstrated that the
      implants in Group A significantly accelerated bone regeneration compared with the
      other implants based on X-rays, histological and biomechanical examinations.
      Therefore, we conclude this novel peptide-modified and gene-activated biomimetic
      bone matrix of TGF-beta1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n is a very promising
      scaffold biomaterial for accelerating bone regeneration.

PMID- 24115368
TI  - Usefulness of MR elastography for predicting esophageal varices in cirrhotic
      patients.
AB  - PURPOSE: To evaluate the usefulness of magnetic resonance elastography (MRE) as a
      noninvasive tool for predicting esophageal varices and identifying high-risk
      varices. MATERIALS AND METHODS: In all, 126 patients with liver cirrhosis, and
      who underwent both MRI including MRE of the liver as well as upper
      gastrointestinal endoscopy for variceal screening within 1 month before or after
      the MRI, were included in this study. The relationship between the liver
      stiffness values measured by MRE and the degree of esophageal varices was
      assessed using Spearman's correlation analysis. In addition, the diagnostic
      performance of MRE for predicting the presence of varices or high-risk varices
      (grade>=II) was evaluated using the receiver-operating characteristics (ROC)
      curves. RESULTS: The mean stiffness values of liver parenchyma measured on MRE
      were well correlated with the grade of esophageal varices (r=0.63). In addition,
      the MRE-based liver stiffness values were significantly lower in the lower-risk
      group than in the higher-risk group (P<0.0001). The area under the ROC curve
      values of MRE for predicting the presence of varices or high-risk varices
      (grade>=II) were 0.859 and 0.810, respectively. Using a liver stiffness cutoff
      value of 5.803 kPa, the sensitivity, specificity, positive predictive value, and
      negative predictive value for predicting high-grade (>=II) esophageal varices
      were 96%, 60%, 36%, and 98%, respectively. CONCLUSION: The MRE-based liver
      stiffness value may be useful for noninvasively predicting esophageal varices and
      identifying high-risk varices in cirrhotic patients.

PMID- 24115367
TI  - Desmoid tumor arising from omohyoid muscle: The first report for unusual
      complication after transaxillary robotic thyroidectomy.
AB  - BACKGROUND: Transaxillary robotic (TAR) thyroidectomy has been performed for
      better aesthetic results by many surgeons. In this report, we describe a rare
      case of a desmoid tumor developed after TAR thyroidectomy, which is speculated to
      be a late-term complication. METHODS AND RESULTS: A 61-year-old woman with a
      history of papillary microcarcinoma had experienced a large left neck mass that
      had grown over 2 years. The patient underwent TAR thyroidectomy (right lobectomy
      and isthmectomy) via the right axilla almost 2.5 years previously. Physical
      examination revealed a 6-cm, firm mass fixed to the left anterior neck. The mass
      was fixed to the omohyoid muscle. The 5.9- * 4.7- * 4.5-cm tumor with the
      surrounding muscles was excised in an en bloc fashion. Pathologic examination
      confirmed the diagnosis of a desmoid tumor. CONCLUSION: This case suggests that
      desmoid tumors could develop late after TAR thyroidectomy. Thus, careful
      observation of the surgical wound may be necessary after TAR thyroidectomy.

PMID- 24115369
TI  - Dapagliflozin treatment for type 2 diabetes: a systematic review and meta
      analysis of randomized controlled trials.
AB  - CONTEXT: Type 2 diabetes has reached epidemic proportions and places a heavy
      burden on society. Dapagliflozin is a novel treatment choice for type 2 diabetes.
      OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was conducted
      to assess the efficacy and safety of dapagliflozin treatment. DATA SOURCES:
      Medline (via PubMed), Embase (via OVID) and the Cochrane Library (up to August
      2012) were searched, and RCTs were collected. STUDY SELECTION: Studies included
      type 2 diabetic subjects, who had been treated with dapagliflozin, and recorded
      HbA1c as outcomes. DATA EXTRACTION: Two reviewers independently assessed articles
      and study quality. Patient characteristics, interventions and outcomes were
      collected. DATA SYNTHESIS: Ten RCTs were included. Risk of bias for outcomes was
      low. Fixed or random effects models were used to pool the results. Dapagliflozin
      treatment was associated with a reduction in HbA1c [weighted mean difference
      (WMD): -0.53%; 95% confidence interval (CI): -0.58% to -0.47%; p < 0.00001],
      fasting plasma glucose (WMD: -1.06 mmol/L; 95% CI: -1.20, -0.92; p < 0.00001),
      and body weight (WMD: -1.63 kg; 95% CI: -1.83, -1.43; p < 0.00001). Dapagliflozin
      monotherapy did not lead to hypoglycaemia [relative risk (RR): 1.44; 95% CI: 0.
      86, 2.41; p = 0.17], although hypoglycaemic risk increased (RR: 1.16; 95% CI:
      1.05, 1.29; p = 0.005) when dapagliflozin was combined with other hypoglycaemic
      drugs. Dapagliflozin increased urinary glucose excretion (WMD: 26.98; 95% CI:
      21.72, 32.24; p < 0.00001) and was associated with an increased risk of urinary
      tract infections (RR: 1.33; 95% CI: 1.10, 1.60; p = 0.004) and genital tract
      infections (RR: 3.23; 95% CI: 2.50, 4.18; p = 0.00001). CONCLUSIONS:
      Dapagliflozin appears to be an effective treatment for type 2 diabetes, although
      it may increase the risk of urinary tract infections and genital tract
      infections.

PMID- 24115370
TI  - Silver-mediated formation of a cofacial porphyrin dimer with the ability to
      intercalate aromatic molecules.

PMID- 24115371
TI  - Adult T-cell leukemia/lymphoma with an unusual CD1a positive phenotype.
AB  - BACKGROUND: Acute T-cell leukemia lymphoma (ATLL) tumor cells generally express
      CD2/CD3/CD5, but lack CD7. These T cells are usually CD4+CD8- and strongly
      express CD25, although some variability in this basic pattern may be found. Here
      we report a case with a very unusual CD1a positive phenotype. METHODS: Samples
      from peripheral blood, bone marrow aspirate, lymph node, and cerebrospinal fluid
      obtained from a 45-year-old male patient with a T-cell lymphoproliferative
      disorder were immunophenotyped by multiparametric flow cytometry. Analysis of
      HTLV-I genome integration in tumoral cells was performed by PCR. RESULTS:
      Neoplastic T cells were cCD3, CD2/CD5/CD30/CD25, and CD1a positive, but
      CD3/CD7/CD4/CD8/CD34/CD10/TdT negative. Serology and integration of HTLV-I were
      positive. CONCLUSION: To the best of our knowledge, CD1a expression has not been
      previously described in this entity. Its detection raised the differential
      diagnosis with acute T lymphoblastic leukemia. The rest of the phenotypic
      markers, the morphology of the neoplastic cells, and the demonstration of HTLV-I
      genome integration provided the final diagnosis.

PMID- 24115372
TI  - NMR spectroscopic studies of intrinsically disordered proteins at near
      physiological conditions.

PMID- 24115373
TI  - Fasting plasma adropin concentrations correlate with fat consumption in human
      females.
AB  - OBJECTIVE: This study investigated whether plasma adropin concentrations are
      influenced by sleep restriction and correlate with dietary preferences. METHODS:
      Plasma adropin concentrations were measured by ELISA using samples from a study
      that investigated feeding behavior in sleep deprived lean (body mass index 22-26
      kg/m(2) ) men and women aged 30-45 y. Sleep (habitual or restricted to 4h/night)
      and diet were controlled during a 4-day inpatient period. On day 5, food was self
      selected (FS). Adropin was measured on day 4 in samples collected throughout the
      day, and then after an overnight fast at 0730 on days 5 (Pre-FS) and 6 (Post-FS).
      RESULTS: Plasma adropin concentrations were not affected by sleep restriction.
      However, circulating adropin concentrations correlated with food selection
      preferences in women, irrespective of sleep status. Pre-FS adropin correlated
      positively with fat intake (total fat, r = 0.867, P < 0.05; saturated fat, r =
      0.959, P < 0.01) and negatively with carbohydrate intake (r = -0.894, P < 0.05)
      as a percent total energy. Post-FS adropin correlated with total (r = 0.797, P <
      0.05) and saturated fat intake (r = 0.945, P < 0.01), and negative with total
      carbohydrate intake (r = -0.929, P < 0.01). Pre-FS adropin also correlated with
      fat intake in kcal adjusted for body size (total fat, r = 0.852, P < 0.05;
      saturated fat, r = 0.927, P < 0.01). CONCLUSIONS: Plasma adropin concentrations
      correlate with fat consumption in women.

PMID- 24115374
TI  - Conversion of cellulose into isosorbide over bifunctional ruthenium nanoparticles
      supported on niobium phosphate.
AB  - Considerable effort has been applied to the development of new processes and
      catalysts for cellulose conversion to valuable platform chemicals. Isosorbide is
      among the most interesting products as it can be applied as a monomer and
      building block for the future replacement of fossil resource-based products. A
      sustainable method of isosorbide production from cellulose is presented in this
      work. The strategy relies on a bifunctional Ru catalyst supported on mesoporous
      niobium phosphate in a H2 atmosphere under pressure without further addition of
      any soluble acid. Over 50 % yield of isosorbide with almost 100 % cellulose
      conversion can be obtained in 1 h. The large surface area, pore size, and strong
      acidity of mesoporous niobium phosphate promote the hydrolysis of cellulose and
      dehydration of sorbitol; additionally, the appropriate size of the supported Ru
      nanoparticles avoids unnecessary hydrogenolysis of sorbitol. Under a
      cellulose/catalyst mass ratio of 43.3, the present bifunctional catalyst could be
      stably used up to six times, with its mesoporous structure well preserved and
      without detectable Ru leaching into the reaction solution. 

PMID- 24115375
TI  - Effects of bicycle helmet laws on children's injuries.
AB  - In recent years, many states and localities in the USA have enacted bicycle
      helmet laws. We estimate the effects of these laws on injuries requiring
      emergency department treatment. Using hospital-level panel data and triple
      difference models, we find helmet laws are associated with reductions in bicycle
      related head injuries among children. However, laws also are associated with
      decreases in non-head cycling injuries, as well as increases in head injuries
      from other wheeled sports. Thus, the observed reduction in bicycle-related head
      injuries may be due to reductions in bicycle riding induced by the laws.

PMID- 24115376
TI  - Subcellular proteomic analysis of human host cells infected with H3N2 swine
      influenza virus.
AB  - Cross-species transmissions of swine influenza viruses (SIVs) raise great public
      health concerns. In this study, subcellular proteomic profiles of human A549
      cells inoculated with H3N2 subtype SIV were used to characterize dynamic cellular
      responses to infection. By 2DE and MS, 27 differentially expressed (13
      upregulated, 14 downregulated) cytoplasmic proteins and 20 differentially
      expressed (13 upregulated, 7 downregulated) nuclear proteins were identified.
      Gene ontology analysis suggested that these differentially expressed proteins
      were mainly involved in cell death, stress response, lipid metabolism, cell
      signaling, and RNA PTMs. Moreover, 25 corresponding genes of the differentially
      expressed proteins were quantitated by real time RT-PCR to examine the
      transcriptional profiles between mock- and virus-infected A549 cells. Western
      blot analysis confirmed that changes in abundance of identified cellular proteins
      heterogeneous nuclear ribonucleoprotein (hnRNP) U, hnRNP C, ALDH1A1, tryptophanyl
      tRNA synthetase, IFI35, and HSPB1 in H3N2 SIV-infected cells were consistent with
      results of 2DE analysis. By confocal microscopy, nucleus-to-cytoplasm
      translocation of hnRNP C and colocalization between the viral nonstructural
      protein 1 and hnRNP C as well as N-myc (and STAT) interactor were observed upon
      infection. Ingenuity Pathway Analysis revealed that cellular proteins altered
      during infection were grouped mainly into NFkappaB and interferon signaling
      networks. Collectively, these identified subcellular constituents provide an
      important framework for understanding host/SIV interactions and underlying
      mechanisms of SIV cross-species infection and pathogenesis. 

PMID- 24115377
TI  - Water- and organo-dispersible gold nanoparticles supported by using ammonium
      salts of hyperbranched polystyrene: preparation and catalysis.
AB  - Gold nanoparticles (1 nm in size) stabilized by ammonium salts of hyperbranched
      polystyrene are prepared. Selection of the R groups provides access to both water
      and organo-dispersible gold nanoparticles. The resulting gold nanoparticles are
      subjected to studies on catalysis in solution, which include reduction of 4
      nitrophenol with sodium borohydride, aerobic oxidation of alcohols, and
      homocoupling of phenylboronic acid. In the reduction of 4-nitrophenol, the
      catalytic activity is clearly dependent on the size of the gold nanoparticles.
      For the aerobic oxidation of alcohols, two types of biphasic oxidation are
      achieved: one is the catalyst dispersing in the aqueous phase, whereas the other
      is in the organic phase. The catalysts are reusable more than four times without
      loss of the catalytic activity. Selective synthesis of biphenyl is achieved by
      the homocoupling of phenylboronic acid catalyzed by organo-dispersible gold
      nanoparticles.

PMID- 24115378
TI  - Effect of starvation on lipophorin density in fifth instar larval Manduca sexta.
AB  - Lipophorin (Lp) is a major insect lipoprotein and is responsible for lipid
      transport between organs. In this study, the effect of starvation on Lp
      properties was analyzed in larval Manduca sexta during the fifth instar. Lp
      hemolymph concentrations in larvae at days 1 and 2 were around 2-3 mg/ml and at
      day 3 it increased to 8 mg/ml. When larvae were starved for 24 h, they did not
      grow, but their body mass and hemolymph volume did not decrease significantly.
      Differences in Lp densities were observed. In fed larvae, from days 1 to 4, two
      major Lp populations were found with densities of 1.124 +/- 0.002 (high density
      Lp-larval1 , HDLp-L1 ) and 1.141 +/- 0.002 g/ml (HDLp-L2 ). When larvae were
      starved for 24 h, only one Lp population was present, with density 1.114 +/-
      0.001 g/ml (HDLp-Ls ). When larvae were abdominally ligated at day 1 or 2 of
      fifth instar, only HDLp-Ls was found after 24 h, indicating that the formation of
      this HDLp population was not dependent on any factor released by head. On the
      other hand, larvae that were ligated at day 3 showed the same Lp populations as
      the fed ones. In 24-h starved larvae, lipid load in Lp was higher as compared to
      the fed controls. In 24-h ligated larvae Lp lipid content increased when ligation
      was performed on day 1 or 2, but not on day 3. So, different responses to
      starvation can be observed depending on the developmental phase of the same
      larval instar. 

PMID- 24115379
TI  - An extensive n, pi, sigma-electron delocalized Si(4) ring.
AB  - The tetrasilacyclobutadiene [LSi(MU-SiL')2 SiL] (L=PhC(NtBu)2 , L'=2,6-iPr2 C6 H3
      NSiMe3 ) consists of an aromatic silicon-containing four-membered ring in which
      two pi, two sigma, and two lone-pair electrons are cyclically delocalized. The
      electron delocalization was illustrated by theoretical studies and reactivity
      with elemental sulfur to form the allylic zwitterionic cyclic compound [(LSi)2
      (MU-SiL')(MU-Si(S)L')] with 2pi-electron delocalization along the Si3 skeleton. 

PMID- 24115380
TI  - Disturbance legacies and climate jointly drive tree growth and mortality in an
      intensively studied boreal forest.
AB  - Most North American forests are at some stage of post-disturbance regrowth,
      subject to a changing climate, and exhibit growth and mortality patterns that may
      not be closely coupled to annual environmental conditions. Distinguishing the
      possibly interacting effects of these processes is necessary to put short-term
      studies in a longer term context, and particularly important for the carbon
      dense, fire-prone boreal forest. The goals of this study were to combine
      dendrochronological sampling, inventory records, and machine-learning algorithms
      to understand how tree growth and death have changed at one highly studied site
      (Northern Old Black Spruce, NOBS) in the central Canadian boreal forest. Over the
      1999-2012 inventory period, mean tree diameter increased even as stand density
      and basal area declined significantly. Tree mortality averaged 1.4 +/- 0.6% yr
      (1), with most mortality occurring in medium-sized trees; new recruitment was
      minimal. There have been at least two, and probably three, significant influxes
      of new trees since stand initiation, but none in recent decades. A combined tree
      ring chronology constructed from sampling in 2001, 2004, and 2012 showed several
      periods of extreme growth depression, with increased mortality lagging depressed
      growth by ~5 years. Higher minimum and maximum air temperatures exerted a
      negative influence on tree growth, while precipitation and climate moisture index
      had a positive effect; both current- and previous-year data exerted significant
      effects. Models based on these variables explained 23-44% of the ring-width
      variability. We suggest that past climate extremes led to significant mortality
      still visible in the current forest structure, with decadal dynamics superimposed
      on slower patterns of fire and succession. These results have significant
      implications for our understanding of previous work at NOBS, the carbon
      sequestration capability of old-growth stands in a disturbance-prone landscape,
      and the sustainable management of regional forests in a changing climate.

PMID- 24115381
TI  - Hair analysis as a tool to evaluate the prevalence of synthetic cannabinoids in
      different populations of drug consumers.
AB  - Among the new psychoactive products, herbal mixtures containing synthetic
      cannabimimetics are likely the most abused worldwide. In this study, a specific
      ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS) method for the detection of 23 synthetic cannabinoids in hair samples was
      developed in order to (1) expand the number of screened compounds, coherent with
      new substances emerging in the European territory, (2) evaluate their consumption
      on a large period of examination, and (3) evaluate the diffusion of
      cannabimimetics among different populations of drug consumers. The method employs
      digestion of hair sample with NaOH followed by extraction with n
      hexane/ethylacetate, and injection into the UHPLC-MS/MS system. After validation,
      the method was applied to the analysis of 344 hair samples previously tested in
      our laboratory for the most common drugs. Overall, 15 samples were found positive
      for at least one synthetic cannabinoid. Coherent with previously published
      results, the present data show that young males, former or still active Cannabis
      consumers, represent the population most often involved in synthetic
      cannabimimetics consumption. Several cases of poly-abuse were also determined.
      The drug most frequently detected was JWH-073 (11 samples) generally at low
      concentration (mean 7.69 +/- 14.4 pg/mg, median 1.9 pg/mg, range 1.6-50.5 pg/mg),
      followed by JWH-122 (8 samples, mean concentration: 544 +/- 968 pg/mg, median
      28.4 pg/mg, range 7.4-2800 pg/mg). Other detected drugs included JWH-250, JWH
      081, JWH-018, JWH-210, JWH-019, and AM-1220. For several positive samples, the
      synthetic cannabinoid concentration was lower than 50 pg/mg, underlining the need
      for established cut-off values for discrimination between chronic consumption and
      occasional use (or external contamination).

PMID- 24115382
TI  - Vibration-assisted crystallization improves organic/dielectric interface in
      organic thin-film transistors.
AB  - Solution processability of organic semiconductors allows high-throughput
      fabrication on arbitrary substrates at low-cost, but the films often exhibit low
      performance. Here, we report on a new method for device fabrication, vibration
      assisted crystallization (VAC) that produces superior films, which approach the
      fundamental performance limits shown in corresponding single-crystal
      measurements. 

PMID- 24115383
TI  - A triruthenium complex capped by a triply bridging oxoboryl ligand.

PMID- 24115384
TI  - Assessing patients with hepatocellular carcinoma meeting the Milan criteria: Is
      liver 3 tesla MR with gadoxetic acid necessary in addition to liver CT?
AB  - PURPOSE: To determine the added value of 3 Tesla liver MR in patients with
      hepatocellular carcinoma (HCC) within the liver computed tomography (CT) -based
      Milan criteria. MATERIALS AND METHODS: Liver CT and MR images of 130 patients
      with HCC within the Milan criteria based on liver CT were retrospectively
      reviewed. The number of MR-diagnosed HCCs and that of high risk hypervascular
      nodules (HRHNs), the effect of obtaining MR on patient management and CT
      appearances of MR-diagnosed HCCs and those of HRHNs were evaluated. Independent
      predictor for diagnosing additional HCCs on liver MR was analyzed. RESULTS: A
      total of 18.5% (24/130) of patients had additional 39 HCCs on MR, with a 5.4%
      (7/130) dropout rate from the Milan criteria. 28.5% (37/130) of patients had
      additional 78 HRHNs. Overall, 39.2% (51/130) of patients required changes in
      management. The common CT appearances of MR-diagnosed HCCs were arterial
      enhancing lesions >= 0.5cm (38.4%, 15/39), low density nodules < 1.5 cm (30.8%,
      12/39) and invisibility (28.2%, 11/39). For MR-diagnosed HRHNs, 55.1% (43/78)
      were invisible on CT. The presence of inconclusive lesions on CT was an
      independent predictor for diagnosing additional HCCs on MR. CONCLUSION: For
      patients with HCCs within the Milan criteria on liver CT, liver MR may be
      necessary to detect additional HCCs and HRHNs.

PMID- 24115385
TI  - Supraglottic immunoglobulin-G4 related plasma cell granuloma: case report and
      literature review.
AB  - BACKGROUND: Granuloma of the upper aerodigestive tract is a rare presentation of
      immunoglobulin-G4 (IgG4)-related disease. Since the disease process was defined
      in 2003, only 2 cases affecting the laryngopharynx have been reported in the
      literature. METHODS AND RESULTS: A 62-year-old white man presented with
      persistent productive cough of brown sputum, globus symptoms, dysphagia,
      odynophagia, dysphonia, otalgia, and general malaise over a period of 2 months.
      Investigations revealed IgG4-positive plasma cell granuloma of the supraglottic
      region. This was successfully treated with oral corticosteroids. CONCLUSION:
      Because IgG4 testing is not performed routinely, management recommendations have
      been poorly defined. We reviewed the literature and discuss herein the clinical
      characteristics, pathology, diagnosis, and management. The authors theorize that
      IgG4-related disease involving the larynx and pharynx may be more common than
      suggested by the paucity of reported cases.

PMID- 24115386
TI  - Critical components of the pluripotency network are targets for the p300/CBP
      interacting protein (p/CIP) in embryonic stem cells.
AB  - p/CIP, also known as steroid receptor coactivator 3 (SRC-3)/Nuclear Receptor
      Coactivator 3 (NCoA3), is a transcriptional coactivator that binds liganded
      nuclear hormone receptors, as well as other transcription factors, and
      facilitates transcription through direct recruitment of accessory factors. We
      have found that p/CIP is highly expressed in undifferentiated mouse embryonic
      stem cells (mESCs) and is downregulated during differentiation. siRNA-mediated
      knockdown of p/CIP decreased transcript levels of Nanog, but not Oct4 or Sox2.
      Microarray expression analysis showed that Klf4, Tbx3, and Dax-1 are
      significantly downregulated in mESCs when p/CIP is knocked down. Subsequent
      chromatin immunoprecipitation (ChIP) analysis demonstrated that Tbx3, Klf4, and
      Dax-1 are direct transcriptional targets of p/CIP. Using the piggyBac
      transposition system, a mouse ESC line that expresses Flag-p/CIP in a doxycycline
      dependent manner was generated. p/CIP overexpression increased the level of
      target genes and promoted the formation of undifferentiated colonies.
      Collectively, these results indicate that p/CIP contributes to the maintenance of
      ESC pluripotency through direct regulation of essential pluripotency genes. To
      better understand the mechanism by which p/CIP functions in ESC pluripotency, we
      integrated our ChIP and transcriptome data with published protein-protein
      interaction and promoter occupancy data to draft a p/CIP gene regulatory network.
      The p/CIP gene regulatory network identifies various feed-forward modules
      including one in which p/CIP activates members of the extended pluripotency
      network, demonstrating that p/CIP is a component of this extended network.

PMID- 24115388
TI  - Cluster screening: an effective approach for probing the substrate space of
      uncharacterized cytochrome P450s.
AB  - Cytochrome P450 monooxygenases (P450s) are versatile enzymes with high potential
      for biocatalysis. The number of newly annotated P450 genes has been increasing
      constantly, and these thus represent a rich resource for new biocatalysts.
      However, the substrate scopes of newly identified P450s are often not known, and
      thus their exploitation is difficult. Herein we describe an approach, named
      "cluster screening", and its application for the primary characterization of two
      P450s: CYP154E1 and CYP154A8. A library comprising 51 compounds was designed and
      organized into nine groups according to their chemical properties. The activities
      of both P450s in vitro were maintained with suitable nonphysiological redox
      partners, and the cluster library was screened with these enzymes for product
      formation. From this library, 30 compounds tested positive for CYP154E1 and 23
      were positive for CYP154A8. Cluster screening distinguishes subtle differences in
      activity and selectivity of enzymes as closely related as those of the same P450
      family. For example, the alkaloid pergolide mesylate was converted by CYP154E1 (4
      %) but not by CYP154A8. A building block of vitamin D3 , Grundmann's ketone, was
      converted by both enzymes, although conversion was higher with CYP154E1 (100 vs
      53%).

PMID- 24115387
TI  - Targeted deep resequencing identifies MID2 mutation for X-linked intellectual
      disability with varied disease severity in a large kindred from India.
AB  - We report a novel missense mutation (c.1040G>A, p.Arg347Gln) in MID2, which
      encodes ubiquitin ligase E3, as the likely cause of X-linked mental retardation
      in a large kindred. The mutation was observed in all affected and obligate
      carriers but not in any unaffected males of the family or in population controls
      (n = 200). When transiently expressed in HEK293T cell line, the mutation was
      found to abolish the function of the COS domain in the protein. The GFP-tagged
      mutant protein accumulated in the cytoplasm instead of binding to the
      cytoskeleton resulting in its altered subcellular localization. Screening of
      coding exons of this gene in additional 480 unrelated individuals with idiopathic
      intellectual disability identified another novel variation p.Asn343Ser. This
      study highlights the growing role of the ubiquitin pathway in intellectual
      disability and also, the difference in MID2 determined phenotype observed in this
      study compared with that of its paralogue MID1 reported in literature. 

PMID- 24115389
TI  - Do cortisol and corticosterone play the same role in coping with stressors?
      Measuring glucocorticoid serum in free-ranging guanacos (Lama guanicoe).
AB  - Habitat can constrain and shape successful ecological and physiological
      strategies, thus providing the context for the evolution of life-history traits.
      However, unpredictable challenges, such as storms, natural disasters, and human
      activities can also have great effects on stress. Glucocorticoids (GCs) are
      adrenal steroid hormones that play an important role in how vertebrates cope with
      these predictable and unpredictable environmental challenges. Although assessing
      GCs levels can have many applications in the study of wildlife and/or captive
      animals, with or without capturing individuals, it requires a species-specific
      complete validation (analytical and biological) before its use. In this work, our
      aim was to: (a) validate a radioimmunoassay (RIA) for measuring GCs levels in L.
      guanicoe serum; (b) assess cortisol and corticosterone levels (if present) in
      serum of wild L. guanicoe individuals; and (c) compare the response to acute
      stressors (handling, shearing, and release). Our results successfully: (a)
      validated RIA for asses GCs levels in wild ungulates; (b) confirmed the presence
      for cortisol and corticosterone and showed that both GCs are differently affected
      by environmental stimuli in L. guanicoe; and (c) showed that GCs exhibit
      different patterns in the field and in response to acute stressors, making these
      camelids an interesting endocrinological model when seeking the adaptive
      functions of a given variation and further emphasizing the complexity of GC
      physiology in wild mammals.

PMID- 24115390
TI  - Crystalline supramolecular nanofibers based on dehydrobenzoannulene derivatives.
AB  - Supramolecular nanofibers (SNFs) composed of low-molecular-weight pi-conjugated
      molecules exhibit attractive optical and electrical properties and are expected
      to be the next optoelectronic materials. In this work, five crystalline SNFs have
      been constructed from three dehydrobenzoannulene (DBA) derivatives. The DBAs were
      designed to assemble in one dimension in a strategy based on anisotropic crystal
      growth. The crystallinity of the SNFs allowed the molecular arrangements in the
      SNFs to be determined. Therefore the mechanism of construction and correlations
      between the molecular arrangements and optical and electrical properties could be
      considered. The results clearly indicate that the properties of the SNFs are
      affected by the chemical structures and molecular arrangements. Moreover, one of
      the SNFs exhibits a high charge-carrier mobility (SigmaMU=0.61 cm(2) V(-1) s(-1))
      because of its crystallinity and appropriate molecular arrangement. This
      systematic experimental study based on a proposed strategy has provided
      information for improving the electrical properties of SNFs. This strategy will
      lead to highly functional SNFs.

PMID- 24115392
TI  - Abusive drinking after liver transplantation is associated with allograft loss
      and advanced allograft fibrosis.
AB  - In patients who undergo liver transplantation for alcoholic liver disease (ALD),
      alcohol relapse is common. A return to abusive or excessive drinking likely
      decreases overall survival; however, the effects of alcohol use on allograft
      outcomes and histopathology are less well defined. We reviewed all cases of liver
      transplantation with ALD as an indication between January 1, 1995 and December
      31, 2007. Allograft outcomes and histopathological results were compared for
      patients who relapsed into alcohol use and patients who maintained abstinence.
      Three hundred patients who underwent transplantation for ALD during this period
      survived at least 1 year, and 48 (16.0%) relapsed into alcohol use that came to
      clinical attention. The pattern of relapse was a single event for 10 patients
      (20.8%), intermittent relapses for 22 patients (45.8%), and continuous heavy
      drinking for 16 patients (33.3%). Continuous heavy drinking was associated with
      allograft loss in a univariate Cox proportional hazards analysis [hazard ratio
      (HR) = 2.43, 95% confidence interval (CI) = 1.26-4.68, P = 0.008] and in a
      multivariate Cox proportional hazards regression (HR = 2.57, 95% CI = 1.32-5.00,
      P = 0.006). A matched-pair analysis that controlled for the hepatitis C virus
      status and the time to biopsy compared the results of allograft histopathology
      for patients who relapsed into alcohol use and patients who maintained
      abstinence. Significant steatosis [odds ratio (OR) = 3.46, 95% CI = 1.29-9.31, P
      = 0.01], steatohepatitis (OR = 6.2, 95% CI = 1.70-22.71, P = 0.006), and advanced
      (stage 3 or higher) fibrosis (OR = 23.18, 95% CI = 3.01-177.30, P = 0.003) were
      associated with alcohol relapse. In conclusion, alcohol relapse after liver
      transplantation (particularly heavy drinking) is associated with decreased graft
      survival and advanced allograft fibrosis.

PMID- 24115393
TI  - Controllable multicolor upconversion luminescence by tuning the NaF dosage.
AB  - Multicolor upconversion (UC) luminescence of NaYF4:Yb(3+)/Er(3+) nanoparticles
      (NPs) was successfully tuned by simply controlling the NaF dosage. Unlike UC
      nanocrystals previously reported in the literature with multicolor emission
      obtained by varying the rare-earth dopants, the current work developed a new
      approach to tune the UC emission color by controlling the NaF concentration
      without changing the ratio and dosage of rare-earth ions. TEM and powder XRD were
      used to characterize the shape, size, and composition of the UC luminescent
      nanocrystals. The luminescence images, emission spectra, and multicolor emission
      mechanism of the NPs have also been demonstrated. As a result of the excellent
      ability of this new method to manipulate color emission, this will open up new
      avenues in the areas of bioprobes, light-emitting devices, color displays,
      lasers, and so forth. To demonstrate their biological applications, the water
      stable, biocompatible, and bioconjugatable NaYF4:Yb(3+)/Er(3+) @poly(acrylic
      acid) NPs were synthesized by this developed strategy and applied in targeted
      cell UC luminescence imaging.

PMID- 24115394
TI  - Laparoscopic robot-assisted major hepatectomy.
AB  - BACKGROUND: We herein present a systematic review of English literature on robot
      assisted major hepatectomy (MH). METHODS: Major hepatectomy was defined as
      resection of three or more liver segments. A literature search was performed
      using the Pubmed database. Articles containing more than five robotic MH were
      selected. In case of multiple publications from the same institution, only the
      most recent article was considered in order to avoid double counting of patients
      between series. RESULTS: Five articles were included in this review. A total of
      68 robotic MH were analyzed, including 38 right hepatectomies and 30 left
      hepatectomies. There were no deaths. Two right hepatectomies (5.2%) and one left
      hepatectomy (3.3%) were converted to open surgery. Weighted average of operative
      time and intraoperative blood loss were 418.6 min and 411.4 ml, respectively.
      Four patients received blood transfusions (6.3%) and 17 developed postoperative
      complications (26.9%). Information on tumor type were available for 57 patients
      of whom 42 were diagnosed with malignant tumors (73.6%) and 15 with benign
      diseases (26.3%). No port site metastasis, peritoneal carcinomatosis, or
      intrahepatic recurrence were reported. Three patients had microscopic margin
      positivity. CONCLUSIONS: Major hepatectomy can be performed under robotic
      assistance. Further experience is needed before final conclusions can be drawn.

PMID- 24115395
TI  - Evaluation of a novel tetra-functional branched poly(ethylene glycol) crosslinker
      for manufacture of crosslinked, decellularized, porcine aortic valve leaflets.
AB  - To address concerns over limitations in the clinical use of glutaraldehyde (GA)
      fixation in bioprosthetic heart valves, we manufactured novel, branched
      poly(ethylene glycol) tetraacrylate (PEG-TA) crosslinked valve leaflets and
      evaluated cytotoxic, thrombogenic, hemolytic, and anticalcification effects,
      thermal stability, and mechanical properties, in comparison to decellularized
      valves (control) and GA crosslinked valves. Thermal denaturation temperatures
      were higher for PEG-TA valve leaflets compared to control and GA crosslinked
      valves (p < 0.001). Leaflet hydrolyzation rate was lower for the PEG-TA group
      than for GA and control groups (p < 0.05). Superior cytocompatibility was found
      for PEG-TA group leaflets (MTT, p < 0.01. apoptosis assay, p > 0.05). No
      thrombogenesis was found in platelet activation tests (p < 0.0001). Hemolysis
      assays showed that PEG-TA leaflets would not cause damage to blood cells (p >
      0.05). Excellent anticalcification properties were confirmed by von Kossa
      staining, western blot, and atomic absorption spectroscopy (p < 0.0001) in a rat
      subcutaneous embedding model. Finally, the novel PEG-TA crosslinked material
      exhibits improved mechanical properties as compared to GA crosslinked materials
      (tensile strength, p < 0.001, Young's modulus, p < 0.001). On the basis of all
      results presented, it is clear that the performance characteristics of PEG-TA
      crosslinked valve leaflets make PEG-TA crosslinked leaflets a promising
      alternative for the next generation of bioprosthetic heart valve.

PMID- 24115396
TI  - Interaction of SH-SY5Y cells with nanogratings during neuronal differentiation:
      comparison with primary neurons.
AB  - Controlling neuronal cell adhesion, migration, and axonal outgrowth via contact
      interactions with biomaterials is a critical element for tissue engineering
      applications and for developing artificial neuronal interfaces. One promising
      approach relies on the exploitation of nanostructured surfaces. Here, the human
      neuroblastoma cell line SH-SY5Y is interfaced with plastic nanogratings (NGs;
      anisotropic topographies composed by alternating lines of grooves and ridges with
      sub-micrometer lateral dimension). The SH-SY5Y cells' (SHs) contact guidance is
      investigated under proliferating conditions and upon differentiation after
      treatment with retinoic acid (RA) and brain-derived neurotrophin factor (BDNF),
      and compared with mouse primary hippocampal neurons (HNs). Quantitative readouts
      are obtained by measuring changes in tubulin cytoskeleton organization and cell
      morphology induced by mechanotransduction. Results demonstrate that SHs
      effectively retrieve substrate topographical signals, in particular during
      differentiation. Remarkably, RA/BDNF improves SH responsiveness to NG directional
      cues, and significantly enhances the alignment to the NG lines. HNs behave
      similarly, showing a marked change in network organization if cultured on NGs.
      These results might help the rational engineering of neuro-regenerative scaffolds
      to improve peripheral nerve wound healing, as well as to investigate the basic
      mechanisms of neuronal wiring. 

PMID- 24115397
TI  - Inter-provider comparison of patient-reported outcomes: developing an adjustment
      to account for differences in patient case mix.
AB  - This paper describes the development of a methodology for the case-mix adjustment
      of patient-reported outcome measures (PROMs) data permitting the comparison of
      outcomes between providers on a like-for-like basis. Statistical models that take
      account of provider-specific effects form the basis of the proposed case-mix
      adjustment methodology. Indirect standardisation provides a transparent means of
      case mix adjusting the PROMs data, which are updated on a monthly basis. Recently
      published PROMs data for patients undergoing unilateral knee replacement are used
      to estimate empirical models and to demonstrate the application of the proposed
      case-mix adjustment methodology in practice. The results are illustrative and are
      used to highlight a number of theoretical and empirical issues that warrant
      further exploration. For example, because of differences between PROMs
      instruments, case-mix adjustment methodologies may require instrument-specific
      approaches. A number of key assumptions are made in estimating the empirical
      models, which could be open to challenge. The covariates of post-operative health
      status could be expanded, and alternative econometric methods could be employed.

PMID- 24115398
TI  - Pathoproteomics of testicular tissue deficient in the GARP component VPS54: the
      wobbler mouse model of globozoospermia.
AB  - In human globozoospermia, round-headed spermatozoa lack an acrosome and therefore
      cannot properly interact with oocytes. In the wobbler (WR) mouse, an L967Q
      missense mutation in the vesicular protein-sorting factor VPS54 causes motor
      neuron degeneration and globozoospermia. Although electron microscopy of WR
      testis shows all major components of spermatogenesis, they appear in a deranged
      morphology that prevents the formation of the acrosome. In order to determine
      proteome-wide changes, affected testes were analysed by 2D-DIGE and MS. The
      concentration of 8 proteins was increased and that of 35 proteins decreased as
      compared to wild type. Mass spectrometric analysis identified proteins with an
      altered concentration to be associated with metabolite transport, fatty acid
      metabolism, cellular interactions, microtubule assembly and stress response
      (chaperones Hsp70-2 and Hsp90alpha). Minor changes were observed for proteins
      involved in cell redox homeostasis, cytoskeleton formation, PTMs, detoxification
      and metabolism. The most dramatically decreased protein in WR testis was
      identified as fatty acid binding protein FABP3, as confirmed by immunoblot
      analysis. We conclude that a missense mutation in VPS54, an essential component
      of the Golgi-associated retrograde protein complex, not only prevents the
      formation of an acrosome but also initiates a cascade of metabolic abnormalities
      and a stress reaction. 

PMID- 24115399
TI  - Coagulation of chitin and cellulose from 1-ethyl-3-methylimidazolium acetate
      ionic-liquid solutions using carbon dioxide.
AB  - Chemisorption of carbon dioxide by 1-ethyl-3-methylimidazolium acetate ([C2
      mim][OAc]) provides a route to coagulate chitin and cellulose from [C2 mim][OAc]
      solutions without the use of high-boiling antisolvents (e.g., water or ethanol).
      The use of CO2 chemisorption as an alternative coagulating process has the
      potential to provide an economical and energy-efficient method for recycling the
      ionic liquid. 

PMID- 24115400
TI  - Strongly phosphorescent palladium(II) complexes of tetradentate ligands with
      mixed oxygen, carbon, and nitrogen donor atoms: photophysics, photochemistry, and
      applications.

PMID- 24115401
TI  - Infiltrative patterns of glioblastoma: Identification of tumor progress using
      apparent diffusion coefficient histograms.
AB  - PURPOSE: To investigate whether apparent diffusion coefficient (ADC) histogram
      analysis can differentiate between patients presenting T2-progress and patients
      presenting stable T2-signal in glioblastoma. MATERIALS AND METHODS: Fourteen
      patients presenting an isolated T2-progress and a matched control group
      exhibiting stable disease were included. Relative ADC value distribution within
      tumoral and peritumoral FLAIR hyperintensities were evaluated using ADC-histogram
      analysis. Severity and frequency of ADC shift between baseline, T2-progress, and
      subsequent T1-progress were analyzed using the Wilcoxon test. RESULTS: The shift
      of ADC histograms either to higher or to lower values in case of T2-progress was
      significantly more severe than in the control group (P value 0.05). Furthermore,
      a significant shift toward lower ADC values (P value 0.02) was detected when
      comparing ADC histograms of patients with T2-progress and subsequent T1-progress.
      CONCLUSION: The basis for the observed ADC shift in isolated T2-progress may be
      time dependent: Initially, formation of peritumoral edema may cause an increase
      of ADC values that is followed by tumor cells infiltrating the surrounding
      tissue, causing a subsequent decrease of ADC values. The shift toward lower ADC
      values in case of subsequent T1-progress confirms this hypothesis and provides
      further evidence for T2-progress being an intermediate step between stable
      disease (SD) and T1-progress.

PMID- 24115402
TI  - Ring expansion of 3-oxetanone-derived spirocycles: facile synthesis of saturated
      nitrogen heterocycles.

PMID- 24115403
TI  - Moose (Alces alces) reacts to high summer temperatures by utilizing thermal
      shelters in boreal forests - an analysis based on airborne laser scanning of the
      canopy structure at moose locations.
AB  - The adaptation of different species to warming temperatures has been increasingly
      studied. Moose (Alces alces) is the largest of the ungulate species occupying the
      northern latitudes across the globe, and in Finland it is the most important game
      species. It is very well adapted to severe cold temperatures, but has a
      relatively low tolerance to warm temperatures. Previous studies have documented
      changes in habitat use by moose due to high temperatures. In many of these
      studies, the used areas have been classified according to how much thermal cover
      they were assumed to offer based on satellite/aerial imagery data. Here, we
      identified the vegetation structure in the areas used by moose under different
      thermal conditions. For this purpose, we used airborne laser scanning (ALS) data
      extracted from the locations of GPS-collared moose. This provided us with
      detailed information about the relationships between moose and the structure of
      forests it uses in different thermal conditions and we were therefore able to
      determine and differentiate between the canopy structures at locations occupied
      by moose during different thermal conditions. We also discovered a threshold
      beyond which moose behaviour began to change significantly: as day temperatures
      began to reach 20  degrees C and higher, the search for areas with higher and
      denser canopies during daytime became evident. The difference was clear when
      compared to habitat use at lower temperatures, and was so strong that it provides
      supporting evidence to previous studies, suggesting that moose are able to modify
      their behaviour to cope with high temperatures, but also that the species is
      likely to be affected by warming climate. 

PMID- 24115404
TI  - Identification of mureidomycin analogues and functional analysis of an N
      acetyltransferase in napsamycin biosynthesis.
AB  - Antibiotic abundance: Several new uridyl peptide antibiotics were identified from
      a heterologous producer strain containing the mureidomycin/napsamycin
      biosynthetic gene cluster by using HRMS and LC-ESI-MS/MS. Analysis of the new
      compounds and the corresponding gene cluster revealed NpsB, an N
      acetyltransferase, to be responsible for acetylation of the uridyl peptide
      antibiotic. 

PMID- 24115405
TI  - Coelomocyte-derived fluorescence and DNA markers of composting earthworm species.
AB  - Supravital species identification of morphologically similar syntopic earthworms
      inhabiting dung and compost heaps or those from commercial cultures is difficult.
      The aim of the studies was to find out non-invasive species-specific markers for
      proper segregation of earthworm species from a dense mixed colony of waste
      decomposers. Worms were segregated according to external characteristics into
      Eisenia andrei, Eisenia fetida, and Dendrobaena veneta, and left for reproduction
      and analysis of non-invasively retrieved coelomocyte-containing coelomic fluid
      and/or species-specific partial sequences of cytochrome c oxidase subunit I (COI)
      gene in DNA extracted from amputated tail tips of adults and their offspring.
      Flow cytometric analysis of coelomocyte samples revealed that amount of nuclear
      DNA increases in order D. veneta ? E. andrei < E. fetida, and intensity of
      eleocyte-derived fluorescence is lower in D. veneta than in Eisenia spp.
      Spectrofluorimetry of coelomocyte lysates revealed that the amount of eleocyte
      stored riboflavin is significantly lower in coelomocyte lysates from D. veneta
      than from Eisenia spp., and the emission peak of X-fluorophore is much more
      distinct in D. veneta than in Eisenia spp. Coelomic fluid of E. andrei exhibits a
      very distinct spectra of MUG fluorophore which are absent in D. veneta and in the
      majority of E. fetida, while some E. fetida possess MUG-like fluorophore.
      Sequences of the COI gene in the DNA of the worms from the mixed colony and their
      offspring confirmed species identity. In conclusion, species-specific coelomocyte
      derived markers may be a useful complement to morphological and DNA-based
      taxonomy during studies on syntopic earthworms.

PMID- 24115411
TI  - Prizes. Higgs and cell studies nab Nobels.

PMID- 24115407
TI  - Recent advances in organocatalytic methods for asymmetric C-C bond formation.
AB  - Beyond a doubt organocatalysis belongs to the most exciting and innovative
      chapters of organic chemistry today. Organocatalysis has emerged not only as a
      complement to metal-catalyzed reactions and to biocatalysis over the last decade,
      but also provides new asymmetric organocatalyzed reactions that cannot be
      accomplished by metal- or biocatalyzed reactions so far. A large number of
      organocatalytic processes are already well established in organic synthesis.
      Nevertheless, the number of publications in this field is still on the increase;
      new important results are produced constantly. This review gives a detailed
      overview of the latest developments and main streams in organocatalyzed
      asymmetric C?C bond formation processes of the last three years. It is intended
      to outline the most important current findings focused on especially new
      synthetic methodologies. 

PMID- 24115406
TI  - Immature muscular tissue differentiation into bone-like tissue by bone
      morphogenetic proteins in vitro, with ossification potential in vivo.
AB  - The objective of this study was to induce bone formation from immature muscular
      tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine
      source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition,
      cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to
      determine their in vivo ossification potential. BMPs, extracted from bovine
      cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks
      culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were
      partially identified by hematoxylin-eosin staining 2 weeks after culture.
      Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in
      the osteoid tissues by immunohistochemical staining. OC gene expression remained
      low, but OP and Col-I were upregulated during the culture period. In vivo
      implanted IMTs showed slight radiopacity 1 week after implantation and strong
      radiopacity 2 and 3 weeks after implantation. One week after implantation,
      migration of numerous capillaries was observed and ossification was detected
      after 2 weeks by histological observation. These results suggest that IMTs are
      able to differentiate into bone-like tissue in vitro, with an ossification
      potential after implantation in vivo.

PMID- 24115412
TI  - Prizes. Cell transport win long overdue.

PMID- 24115413
TI  - Science funding. U.S. shutdown tightens its grip on research.

PMID- 24115414
TI  - Policy. NASA meeting bars Chinese students.

PMID- 24115415
TI  - Dual-use research. Dutch H5N1 ruling raises new questions.

PMID- 24115416
TI  - Psychiatric research. Severe autism, often slighted, now targeted for study.

PMID- 24115418
TI  - Japan. Windfall for tiny university with outsized ambitions.

PMID- 24115417
TI  - Ancient DNA. Farming's tangled European roots.

PMID- 24115419
TI  - Impact theory gets whacked.

PMID- 24115420
TI  - Biology's dry future.

PMID- 24115421
TI  - Retraction. A type I-secreted, sulfated peptide triggers XA21-mediated innate
      immunity.

PMID- 24115423
TI  - A model of strength.

PMID- 24115422
TI  - Working together to prepare for disasters.

PMID- 24115424
TI  - The editor's dilemma.

PMID- 24115426
TI  - Medicine. Newborn screening: gaps in the evidence.

PMID- 24115427
TI  - Neuroscience. What are mini-brains?

PMID- 24115428
TI  - Materials Science. Structure and motion of a 2D glass.

PMID- 24115429
TI  - Applied physics. Directing data center traffic.

PMID- 24115430
TI  - Development. Getting your gut into shape.

PMID- 24115431
TI  - Ecology. Cleaner lakes are dirtier lakes.

PMID- 24115432
TI  - Genetics. GWAS to therapy by genome edits?

PMID- 24115433
TI  - Molecular biology. RNAi, Antiviral after all.

PMID- 24115434
TI  - Evidence for water in the rocky debris of a disrupted extrasolar minor planet.
AB  - The existence of water in extrasolar planetary systems is of great interest
      because it constrains the potential for habitable planets and life. We have
      identified a circumstellar disk that resulted from the destruction of a water
      rich and rocky extrasolar minor planet. The parent body formed and evolved around
      a star somewhat more massive than the Sun, and the debris now closely orbits the
      white dwarf remnant of the star. The stellar atmosphere is polluted with metals
      accreted from the disk, including oxygen in excess of that expected for oxide
      minerals, indicating that the parent body was originally composed of 26% water by
      mass. This finding demonstrates that water-bearing planetesimals exist around A-
      and F-type stars that end their lives as white dwarfs. 

PMID- 24115435
TI  - Femtosecond visualization of lattice dynamics in shock-compressed matter.
AB  - The ultrafast evolution of microstructure is key to understanding high-pressure
      and strain-rate phenomena. However, the visualization of lattice dynamics at
      scales commensurate with those of atomistic simulations has been challenging.
      Here, we report femtosecond x-ray diffraction measurements unveiling the response
      of copper to laser shock-compression at peak normal elastic stresses of ~73
      gigapascals (GPa) and strain rates of 10(9) per second. We capture the evolution
      of the lattice from a one-dimensional (1D) elastic to a 3D plastically relaxed
      state within a few tens of picoseconds, after reaching shear stresses of 18 GPa.
      Our in situ high-precision measurement of material strength at spatial (<1
      micrometer) and temporal (<50 picoseconds) scales provides a direct comparison
      with multimillion-atom molecular dynamics simulations. 

PMID- 24115436
TI  - Imaging atomic rearrangements in two-dimensional silica glass: watching silica's
      dance.
AB  - Structural rearrangements control a wide range of behavior in amorphous
      materials, and visualizing these atomic-scale rearrangements is critical for
      developing and refining models for how glasses bend, break, and melt. It is
      difficult, however, to directly image atomic motion in disordered solids. We
      demonstrate that using aberration-corrected transmission electron microscopy, we
      can excite and image atomic rearrangements in a two-dimensional silica glass
      revealing a complex dance of elastic and plastic deformations, phase transitions,
      and their interplay. We identified the strain associated with individual ring
      rearrangements, observed the role of vacancies in shear deformation, and
      quantified fluctuations at a glass/liquid interface. These examples illustrate
      the wide-ranging and fundamental materials physics that can now be studied at
      atomic-resolution via transmission electron microscopy of two-dimensional
      glasses. 

PMID- 24115437
TI  - RNA interference functions as an antiviral immunity mechanism in mammals.
AB  - Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to
      direct antiviral immunity by RNA interference (RNAi). However, it remains unknown
      whether the mammalian RNAi pathway has a natural antiviral function. Here, we
      show that infection of hamster cells and suckling mice by Nodamura virus (NoV), a
      mosquito-transmissible RNA virus, requires RNAi suppression by its B2 protein.
      Loss of B2 expression or its suppressor activity leads to abundant production of
      viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral
      small RNAs detected during virulent infection by NoV do not have the properties
      of canonical siRNAs. These findings have parallels with the induction and
      suppression of antiviral RNAi by the related Flock house virus in fruit flies and
      nematodes and reveal a mammalian antiviral immunity mechanism mediated by RNAi. 

PMID- 24115438
TI  - Antiviral RNA interference in mammalian cells.
AB  - In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived
      double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide
      ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense,
      viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and
      invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here,
      we show that undifferentiated mouse cells infected with encephalomyocarditis
      virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the
      signature features of siRNAs. These derive from viral dsRNA replication
      intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and
      decrease in abundance upon cell differentiation. Furthermore, genetically
      ablating a NoV-encoded VSR that antagonizes DICER during authentic infections
      reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We
      conclude that antiviral RNAi operates in mammalian cells. 

PMID- 24115439
TI  - RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide
      replication.
AB  - Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that
      disassembles telomere loops (T loops) and suppresses telomere fragility to
      maintain the integrity of chromosome ends. We established that RTEL1 also
      associates with the replisome through binding to proliferating cell nuclear
      antigen (PCNA). Mouse cells disrupted for the RTEL1-PCNA interaction (PIP mutant)
      exhibited accelerated senescence, replication fork instability, reduced
      replication fork extension rates, and increased origin usage. Although T-loop
      disassembly at telomeres was unaffected in the mutant cells, telomere replication
      was compromised, leading to fragile sites at telomeres. RTEL1-PIP mutant mice
      were viable, but loss of the RTEL1-PCNA interaction accelerated the onset of
      tumorigenesis in p53-deficient mice. We propose that RTEL1 plays a critical role
      in both telomere and genome-wide replication, which is crucial for genetic
      stability and tumor avoidance. 

PMID- 24115440
TI  - Human influences on nitrogen removal in lakes.
AB  - Human activities have increased the availability of reactive nitrogen in many
      ecosystems, leading to negative impacts on human health, biodiversity, and water
      quality. Freshwater ecosystems, including lakes, streams, and wetlands, are a
      large global sink for reactive nitrogen, but factors that determine the efficacy
      of freshwater nitrogen removal rates are poorly known. Using a global lake data
      set, we show that the availability of phosphorus, a limiting nutrient, affects
      both annual nitrogen removal rate and efficiency. This result indicates that
      increased phosphorus inputs from human activities have stimulated nitrogen
      removal processes in many lakes. Recent management-driven reductions in
      phosphorus availability promote water column accumulation and export of nitrogen
      from large lakes, an unintended consequence of single-element management that
      argues for greater control of nitrogen as well as phosphorus sources. 

PMID- 24115441
TI  - Type 6 secretion system-mediated immunity to type 4 secretion system-mediated
      gene transfer.
AB  - Gram-negative bacteria use the type VI secretion system (T6SS) to translocate
      toxic effector proteins into adjacent cells. The Pseudomonas aeruginosa H1-locus
      T6SS assembles in response to exogenous T6SS attack by other bacteria. We found
      that this lethal T6SS counterattack also occurs in response to the mating pair
      formation (Mpf) system encoded by broad-host-range IncPalpha conjugative plasmid
      RP4 present in adjacent donor cells. This T6SS response was eliminated by
      disruption of Mpf structural genes but not components required only for DNA
      transfer. Because T6SS activity was also strongly induced by membrane-disrupting
      natural product polymyxin B, we conclude that RP4 induces "donor-directed T6SS
      attacks" at sites corresponding to Mpf-mediated membrane perturbations in
      recipient P. aeruginosa cells to potentially block acquisition of parasitic
      foreign DNA. 

PMID- 24115442
TI  - An erythroid enhancer of BCL11A subject to genetic variation determines fetal
      hemoglobin level.
AB  - Genome-wide association studies (GWASs) have ascertained numerous trait
      associated common genetic variants, frequently localized to regulatory DNA. We
      found that common genetic variation at BCL11A associated with fetal hemoglobin
      (HbF) level lies in noncoding sequences decorated by an erythroid enhancer
      chromatin signature. Fine-mapping uncovers a motif-disrupting common variant
      associated with reduced transcription factor (TF) binding, modestly diminished
      BCL11A expression, and elevated HbF. The surrounding sequences function in vivo
      as a developmental stage-specific, lineage-restricted enhancer. Genome
      engineering reveals the enhancer is required in erythroid but not B-lymphoid
      cells for BCL11A expression. These findings illustrate how GWASs may expose
      functional variants of modest impact within causal elements essential for
      appropriate gene expression. We propose the GWAS-marked BCL11A enhancer
      represents an attractive target for therapeutic genome engineering for the beta
      hemoglobinopathies. 

PMID- 24115445
TI  - The potential of neurofeedback in the treatment of eating disorders: a review of
      the literature.
AB  - Neurofeedback is defined as the training of voluntary regulation of localised
      neural activity using real-time feedback through a brain-computer interface. It
      has shown initial success as a potential clinical treatment tool in proof of
      concept studies, but has yet to be evaluated with respect to eating disorders.
      This paper (i) provides a brief overview of the current status of eating disorder
      treatments; (ii) describes the studies to date that use neurofeedback involving
      electroencephalography, real-time functional magnetic resonance imaging or near
      infrared spectroscopy; and (iii) considers the potential of these technologies as
      treatments for eating disorders.

PMID- 24115446
TI  - Non-invasive high-frequency oscillatory ventilation (n-HFOV). Thoughts about a
      bench model.

PMID- 24115444
TI  - Fueling immunity: insights into metabolism and lymphocyte function.
AB  - Lymphocytes face major metabolic challenges upon activation. They must meet the
      bioenergetic and biosynthetic demands of increased cell proliferation and also
      adapt to changing environmental conditions, in which nutrients and oxygen may be
      limiting. An emerging theme in immunology is that metabolic reprogramming and
      lymphocyte activation are intricately linked. However, why T cells adopt specific
      metabolic programs and the impact that these programs have on T cell function
      and, ultimately, immunological outcome remain unclear. Research on tumor cell
      metabolism has provided valuable insight into metabolic pathways important for
      cell proliferation and the influence of metabolites themselves on signal
      transduction and epigenetic programming. In this Review, we highlight emerging
      concepts regarding metabolic reprogramming in proliferating cells and discuss
      their potential impact on T cell fate and function. 

PMID- 24115443
TI  - Ancient DNA reveals key stages in the formation of central European mitochondrial
      genetic diversity.
AB  - The processes that shaped modern European mitochondrial DNA (mtDNA) variation
      remain unclear. The initial peopling by Palaeolithic hunter-gatherers ~42,000
      years ago and the immigration of Neolithic farmers into Europe ~8000 years ago
      appear to have played important roles but do not explain present-day mtDNA
      diversity. We generated mtDNA profiles of 364 individuals from prehistoric
      cultures in Central Europe to perform a chronological study, spanning the Early
      Neolithic to the Early Bronze Age (5500 to 1550 calibrated years before the
      common era). We used this transect through time to identify four marked shifts in
      genetic composition during the Neolithic period, revealing a key role for Late
      Neolithic cultures in shaping modern Central European genetic diversity. 

PMID- 24115447
TI  - Comparative proteomics evaluation of plasma exosome isolation techniques and
      assessment of the stability of exosomes in normal human blood plasma.
AB  - Exosomes are nanovesicles released by a variety of cells and are detected in body
      fluids including blood. Recent studies have highlighted the critical application
      of exosomes as personalized targeted drug delivery vehicles and as reservoirs of
      disease biomarkers. While these research applications have created significant
      interest and can be translated into practice, the stability of exosomes needs to
      be assessed and exosome isolation protocols from blood plasma need to be
      optimized. To optimize methods to isolate exosomes from blood plasma, we
      performed a comparative evaluation of three exosome isolation techniques
      (differential centrifugation coupled with ultracentrifugation, epithelial cell
      adhesion molecule immunoaffinity pull-down, and OptiPrep(TM) density gradient
      separation) using normal human plasma. Based on MS, Western blotting and
      microscopy results, we found that the OptiPrep(TM) density gradient method was
      superior in isolating pure exosomal populations, devoid of highly abundant plasma
      proteins. In addition, we assessed the stability of exosomes in plasma over 90
      days under various storage conditions. Western blotting analysis using the
      exosomal marker, TSG101, revealed that exosomes are stable for 90 days.
      Interestingly, in the context of cellular uptake, the isolated exosomes were able
      to fuse with target cells revealing that they were indeed biologically active. 

PMID- 24115448
TI  - Preparation and hydrogen sorption performances of BCNO porous microbelts with
      ultra-narrow and tunable pore widths.

PMID- 24115449
TI  - The development of an in vitro test method for predicting the abrasion resistance
      of textile and metal components of endovascular stent grafts.
AB  - Implantable endovascular stent grafts have become a frequent option for the
      treatment of abdominal and thoracic aneurysms. Given that such devices are
      permanent implants, the question of long-term biostability needs to be addressed.
      This article describes the development of an in vitro stent graft abrasion test
      method between the graft fabric and metal stent of an endovascular device. Three
      endpoints were established to determine the abrasion resistance between the
      fabric and stent surfaces after a predetermined number of abrasion cycles. During
      initial testing, two types of graft fabric materials, multifilament woven
      polyester fabric and monofilament woven polyester fabric, and two types of stent
      materials, laser cut nitinol stents and regular nitinol stent wire, were
      evaluated under dry and wet conditions. The results have shown that this test
      method is viable for testing the relative abrasion resistance of the components
      of endovascular stent grafts. The abrasion resistance of both fabrics was lower
      in a wet environment compared to being tested dry. Additionally, the
      multifilament polyester fabric had better abrasion resistance than the
      monofilament polyester fabric. The laser cut nitinol stent was more aggressive in
      creating holes and breaking yarns, while the regular nitinol stent wire caused a
      greater loss in fabric strength.

PMID- 24115451
TI  - Can data envelopment analysis provide a scalar index of 'value'?
AB  - The concept of 'value' typically includes a combination of cost and quality
      measures. Some approaches to incorporating value into payment systems treat cost
      and quality as separate dimensions, but policymakers have expressed interest in a
      single scalar index that combines cost and quality. Treating risk-adjusted cost
      as an input and multiple measures of quality as outputs, we examine whether data
      envelopment analysis input efficiency is associated with higher quality and lower
      cost in a sample of physician practices using 2008 US Medicare claims data from
      Colorado. The findings suggest that input efficiency might provide a useful
      scalar measure of value for a value-based payment system for physician services.

PMID- 24115450
TI  - GALNT12 is not a major contributor of familial colorectal cancer type X.
AB  - Previous evidence indicates that mutations in the GALNT12 gene might cause a
      fraction of the unexplained familial colorectal cancer (CRC) cases: GALNT12 is
      located in 9q22-33, in close proximity to a CRC linkage peak; and germline
      missense variants that reduce the enzymatic activity of the protein have been
      identified in CRC patients, some of them with familial CRC history. We
      hypothesized that mutations in GALNT12 might explain part of the high-risk
      families grouped as familial CRC type X (fCRC-X), that is, Amsterdam-positive
      families with mismatch repair proficient tumors. We sequenced the coding regions
      of the gene in 103 probands of fCRC-X families, finding no functionally relevant
      mutations. Our results rule out GALNT12 as a major high CRC susceptibility gene.
      Additional studies are required to provide further evidence about its role as a
      moderate/low susceptibility gene in familial aggregation of cancer. 

PMID- 24115452
TI  - Generation of HNO and HSNO from nitrite by heme-iron-catalyzed metabolism with
      H2S.

PMID- 24115453
TI  - Palladium-catalyzed direct functionalization of 2-aminobutanoic acid derivatives:
      application of a convenient and versatile auxiliary.

PMID- 24115455
TI  - Bicyclic peptide inhibitor of urokinase-type plasminogen activator: mode of
      action.
AB  - The development of protease inhibitors for pharmacological intervention has taken
      a new turn with the use of peptide-based inhibitors. Here, we report the rational
      design of bicyclic peptide inhibitors of the serine protease urokinase-type
      plasminogen activator (uPA), based on the established monocyclic peptide, upain
      2. It was successfully converted to a bicyclic peptide, without loss of
      inhibitory properties. The aim was to produce a peptide cyclised by an amide bond
      with an additional stabilising across-the-ring covalent bond. We expected this
      bicyclic peptide to exhibit a lower entropic burden upon binding. Two bicyclic
      peptides were synthesised with affinities similar to that of upain-2, and their
      binding energetics were evaluated by isothermal titration calorimetry. Indeed,
      compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon
      binding to uPA. We also investigated the solution structures of the bicyclic
      peptide by NMR spectroscopy to map possible conformations. An X-ray structure of
      the bicyclic-peptide-uPA complex confirmed an interaction similar to that for the
      previous upain-1/upain-2-uPA complexes. These physical studies of the peptide
      protease interactions will aid future designs of bicyclic peptide protease
      inhibitors.

PMID- 24115454
TI  - Optimized simultaneous ASL and BOLD functional imaging of the whole brain.
AB  - PURPOSE: To compare a double-excitation combined arterial-spin labeling/blood
      oxygenation level dependent (ASL/BOLD) functional imaging method to a double-echo
      method. ASL provides a useful complement to standard BOLD functional imaging, to
      map effects of cerebral hemodynamics. Whole-brain imaging is necessary to
      properly characterize large functional networks. A challenge of whole-brain
      ASL/BOLD is that images for ASL functional contrast must be acquired before
      significant longitudinal relaxation of the inverted spins occurs; however, a
      longer echo time (TE) is required for optimal BOLD functional contrast,
      lengthening the acquisition time. Thus, existing combined ASL/BOLD studies have
      only partial-brain coverage. MATERIALS AND METHODS: The proposed method allows
      acquisition of images for ASL contrast within a short period after the ASL
      labeling pulse and postinversion delay, then subsequent acquisition of images
      with longer TE for BOLD contrast. The technique is demonstrated using a narrative
      comprehension task in 35 normal children, and the double-excitation method is
      empirically compared with the double-echo method in 7 normal adults. RESULTS:
      Compared with a double-echo sequence, simulations show the double-excitation
      method improves ASL contrast-to-noise ratio (CNR) (~50%) in later-acquired slices
      with minimal (<1%) reduction in BOLD CNR in earlier-acquired slices if reduced
      excitation flip angles for the ASL acquisitions are used. Empirical results from
      adult data are in agreement with the simulations. Group analyses from the
      narrative comprehension task also show greater intersubject sensitivity in BOLD
      versus ASL. CONCLUSION: Our method simultaneously optimizes ASL and BOLD
      acquisitions for CNR while economizing acquisition time.

PMID- 24115456
TI  - Tall shrub and tree expansion in Siberian tundra ecotones since the 1960s.
AB  - Circumpolar expansion of tall shrubs and trees into Arctic tundra is widely
      thought to be occurring as a result of recent climate warming, but little
      quantitative evidence exists for northern Siberia, which encompasses the world's
      largest forest-tundra ecotonal belt. We quantified changes in tall shrub and tree
      canopy cover in 11, widely distributed Siberian ecotonal landscapes by comparing
      very high-resolution photography from the Cold War-era 'Gambit' and 'Corona'
      satellite surveillance systems (1965-1969) with modern imagery. We also analyzed
      within-landscape patterns of vegetation change to evaluate the susceptibility of
      different landscape components to tall shrub and tree increase. The total cover
      of tall shrubs and trees increased in nine of 11 ecotones. In northwest Siberia,
      alder (Alnus) shrubland cover increased 5.3-25.9% in five ecotones. In Taymyr and
      Yakutia, larch (Larix) cover increased 3.0-6.7% within three ecotones, but
      declined 16.8% at a fourth ecotone due to thaw of ice-rich permafrost. In
      Chukotka, the total cover of alder and dwarf pine (Pinus) increased 6.1% within
      one ecotone and was little changed at a second ecotone. Within most landscapes,
      shrub and tree increase was linked to specific geomorphic settings, especially
      those with active disturbance regimes such as permafrost patterned-ground,
      floodplains, and colluvial hillslopes. Mean summer temperatures increased at most
      ecotones since the mid-1960s, but rates of shrub and tree canopy cover expansion
      were not strongly correlated with temperature trends and were better correlated
      with mean annual precipitation. We conclude that shrub and tree cover is
      increasing in tundra ecotones across most of northern Siberia, but rates of
      increase vary widely regionally and at the landscape scale. Our results indicate
      that extensive changes can occur within decades in moist, shrub-dominated
      ecotones, as in northwest Siberia, while changes are likely to occur much more
      slowly in the highly continental, larch-dominated ecotones of central and eastern
      Siberia. 

PMID- 24115457
TI  - Proteomic analysis of Bacillus subtilis strains engineered for improved
      production of heterologous proteins.
AB  - The use of bacterial systems for recombinant protein production has advantages of
      simplicity, time and cost over competing systems. However, widely used bacterial
      expression systems (e.g. Escherichia coli, Pseudomonas fluorescens) are not able
      to secrete soluble proteins directly into the culture medium. This limits yields
      and increases downstream processing time and costs. In contrast, Bacillus spp.
      secrete native enzymes directly into the culture medium at grams-per-litre
      quantities, although the yields of some recombinant proteins are severely
      limited. We have engineered the Bacillus subtilis genome to generate novel
      strains with precise deletions in the genes encoding ten extracytoplasmic
      proteases that affect recombinant protein secretion, which lack chromosomal
      antibiotic resistance genes. The deletion sites and presence of single nucleotide
      polymorphisms were confirmed by sequencing. The strains are stable and were used
      in industrial-scale fermenters for the production of the Bacillus anthracis
      vaccine protein, protective antigen, the productivity of which is extremely low
      in the unmodified strain. We also show that the deletion of so-called quality
      control proteases appears to influence cell-wall synthesis, resulting in the
      induction of the cell-wall stress regulon that encodes another quality control
      protease. 

PMID- 24115458
TI  - Oxytocin and anorexia nervosa: a review of the emerging literature.
AB  - Anorexia nervosa (AN) is an intractable illness that is difficult to treat. The
      identification of neural correlates and novel agents to transform treatment has
      become priority avenues for research. Oxytocin (OT) is a neuropeptide whose
      emerging sphere of influence on mammalian behaviour and demonstrated impact on
      psychiatric illness suggest it may have potential in AN. In this paper, we
      undertake a targeted summary of the existing literature on OT research as it
      pertains to brain based behaviour and psychiatric dysfunction. Then, we conduct a
      systematic review of OT in AN. Papers that addressed any aspect of the OT system
      in AN were examined. The existing literature, although limited and based on small
      sample sizes, suggests a derangement of the OT system in AN that may normalise
      upon recovery. Preliminary pilot data from unpublished studies suggest a
      potential effect of OT administration on eating-related indices.

PMID- 24115459
TI  - Discrete double-to-quadruple aromatic stacks: stepwise integration of face-to
      face geometries in cocrystals based on indolocarbazole.

PMID- 24115460
TI  - Ten-year follow up of hydroxychloroquine treatment for ABCA3 deficiency.
AB  - We present a child with interstitial lung disease (ILD) who was diagnosed with
      desquamative interstitial pneumonitis following CT thorax and open lung biopsy
      aged 2 years. Subsequently, surfactant protein gene analysis revealed mutations
      in the ABCA3 gene. This case of ABCA3 deficient ILD describes a stable clinical
      course over 10 years and highlights the potential benefit of hydroxychloroquine
      for this condition.

PMID- 24115461
TI  - Biochemical and molecular characterisation and cross-resistance in field and
      laboratory chlorpyrifos-resistant strains of Laodelphax striatellus (Hemiptera:
      Delphacidae) from eastern China.
AB  - BACKGROUND: Laboratory selection is often employed in resistance mechanism
      studies because field-derived populations commonly do not have high enough
      resistance for such studies. In the present study, a field-collected Laodelphax
      striatellus population from eastern China was laboratory selected for
      chlorpyrifos resistance and susceptibility, and the developed strains, along with
      a field population, were studied for cross-resistance and resistance mechanisms
      at biochemical and molecular levels. RESULTS: A 158.58-fold chlorpyrifos
      resistant strain (JH-chl) and a chlorpyrifos-susceptible strain (JHS) were
      established after laboratory selection of 25 generations. Cross-resistance to
      deltamethrin, diazinon, methomyl, carbosulfan, acephate and imidacloprid were
      detected in JH-chl and a field-collected strain (JHF). Synergism and enzyme
      activity data suggested potential involvement of P450s and esterases in JH-chl as
      well as AChE alteration. Furthermore, CYP6AY3v2, CYP306A2v2, CYP353D1v2 and
      LSCE36 genes were significantly overexpressed in JH-chl (6.87-12.14-fold).
      Feeding of dsRNAs reduced the expression of the four target genes (35.6-56.8%)
      and caused significant adult mortality (75.21-88.45%), implying resistance
      reduction. However, mechanism(s) conferring chlorpyrifos resistance in JHF were
      unclear. CONCLUSION: In contrast to previous reports, multiple overexpressed
      detoxification genes were potentially associated with chlorpyrifos resistance, as
      confirmed by RNAi feeding tests. Chlorpyrifos resistance exhibits cross
      resistance with insecticides in the same and different classes.

PMID- 24115462
TI  - It seemed like a good idea at the time.

PMID- 24115463
TI  - Determination of asymmetric and symmetric dimethylarginines in human plasma by
      HPLC with electrochemical detection.
AB  - A new HPLC method was developed and validated for the determination of asymmetric
      and symmetric dimethylarginines and l-arginine in human plasma. After SPE and
      evaporation of the eluate, the samples were derivatised with an o
      phthaldialdehyde reagent containing 3-mercaptopropionic acid. The derivatives
      formed were analysed by isocratic RP-HPLC with electrochemical detection at +320
      mV. The mobile phase consisted of 50 mM phosphate buffer (pH 6.1) containing 10%
      v/v acetonitrile, the flow rate was 1 mL/min. The retention times of all
      compounds including monomethylarginine (internal standard) were <24 min. The LODs
      (S/N 3:1) were 0.012 MUM for both dimethylarginines and 0.013 MUM for L-arginine;
      the linearity of the method was from 0.1 to 20 MUM for both dimethylarginines and
      from 1 to 200 MUM for L-arginine. Absolute extraction recoveries measured for all
      analytes ranged from 85 to 88%.

PMID- 24115464
TI  - Advantages of embedment-free section transmission electron microscopy.
AB  - The usefulness of embedment-free section transmission electron microscopy (TEM)
      is stressed for present and future morphological analyses, and several examples
      are demonstrated which are revealed in sections for the first time by this
      method: en-face views of slit diaphragm of renal glomerulus and fenestrated
      diaphragm of capillary endothelium, transparency of neural myelin, attenuated
      endothelium and some basement laminae, labyrinth architecture of vacuoles within
      lipid droplets, and enhanced 3D effect of ultrastructures, the latter of which is
      the case in electron tomography. In addition, the biological significance of
      structured appearance (microtrabecular lattices) of the cytoplasmic matrix, which
      is disclosed by this method, are briefly reviewed in relation to the sol-gel
      transition of cytoplasmic heterogenous proteins. Since the ultrastructures of
      various cells and tissues in this method are confirmed to be well correspondent
      to those in conventional epoxy section TEM except for isotropic dimensional
      changes, and because there is no necessity for any special expensive equipments
      other than those for the conventional TEM, the embedment-free section TEM method
      with these advantages, deserves much more wide application to the morphological
      research including electron tomography.

PMID- 24115465
TI  - Acceleration of dermal wound healing by using electrospun curcumin-loaded
      poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone)
      fibrous mats.
AB  - This study prepared a composite scaffold composed of curcumin and poly(epsilon
      caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL,
      PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin
      into the polymeric matrix had an obvious effect on the morphology and dimension
      of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the
      cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had
      significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be
      sustainably released from the fibrous scaffolds. More importantly, in vivo
      efficacy in enhancing wound repair was also investigated based on a full
      thickness dermal defect model for Wistar rats. The results indicated that the
      PCEC/curcumin fibrous mats had a significant advantage in promoting wound
      healing. At 21 days post-operation, the dermal defect was basically recovered to
      its normal condition. A percentage of wound closure reached up to 93.3 +/- 5.6%
      compared with 76.9 +/- 4.9% of the untreated control (p < 0.05). Therefore, the
      as-prepared PCEC/curcumin composite mats are a promising candidate for use as
      wound dressing.

PMID- 24115466
TI  - Functional magnetic resonance cholangiography enhanced with Gd-EOB-DTPA: effect
      of liver function on biliary system visualization.
AB  - PURPOSE: To evaluate effect of liver function on biliary system visualization
      using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)
      enhanced magnetic resonance cholangiography (CE-MRC). MATERIALS AND METHODS: In
      all, 39 patients were divided into three groups according to their Child-Pugh
      classification: group A, Child-Pugh class A (23); group B, class B (11); and
      group C, class C (5). They underwent Gd-EOB-DTPA CE-MRC. Biliary system
      visualization was qualitatively rated on a 5-point scale. Relative signal
      intensity (RSI) of common bile duct (CBD) and liver was quantitatively measured.
      Laboratory findings and the Model of Endstage Liver Disease (MELD) score were
      recorded. RESULTS: Visualization ratings of CBD, left hepatic duct, right hepatic
      duct, segmental branches of intrahepatic ducts, cystic duct, and gallbladder of
      group A were: 3.61 +/- 0.58, 2.87 +/- 0.97, 2.96 +/- 0.77, 1.17 +/- 0.58, 3.04 +/
      0.83, 3.00 +/- 0.95, respectively; group B: 2.00 +/- 0.61, 1.09 +/- 0.64, 0.91
      +/- 0.54, 0.27 +/- 0.13, 1.36 +/- 0.62, 1.45 +/- 0.54, respectively; group C:
      1.40 +/- 0.73, 1.00 +/- 0.51, 1.00 +/- 0.51, 0.00 +/- 0.00, 0.60 +/- 0.39, 0.60
      +/- 0.39, respectively. RSI of CBD of groups A to C were 17.12 +/- 0.41, 3.95 +/-
      0.63, 3.33 +/- 0.30, respectively. RSI of liver of groups A to C were 6.73 +/-
      0.72, 2.53 +/- 1.02, 2.05 +/- 0.11, respectively. CE-MRC images of group A were
      significantly better than those of group B and C in terms of both visualization
      ratings and RSI of CBD. CBD RSI positively correlated with liver RSI (r = 0.99, P
      < 0.001). The total serum bilirubin level and MELD score were significant
      predictors of RSI of CBD. CONCLUSION: Different liver function according to Child
      Pugh classification significantly affects biliary system visualization of Gd-EOB
      DTPA CE-MRC.

PMID- 24115467
TI  - The S2 state of the oxygen-evolving complex of photosystem II explored by QM/MM
      dynamics: spin surfaces and metastable states suggest a reaction path towards the
      S3 state.

PMID- 24115468
TI  - Backbone FC-H...O hydrogen bonds in 2'F-substituted nucleic acids.

PMID- 24115469
TI  - Cost-utility analysis of individual psychosocial support interventions for breast
      cancer patients in a randomized controlled study.
AB  - OBJECTIVES: The aim was to explore the cost-utility in providing complementary
      individual psychosocial support to breast cancer patients compared with standard
      care (SC). METHODS: Patients just starting adjuvant therapy (n = 168) at Uppsala
      University Hospital, Sweden, were consecutively included and randomized into
      three groups: psychosocial support from a specially trained nurse (INS), from a
      psychologist (IPS), or SC. Psychological effects and healthcare utilization were
      monitored during a 2-year period. The hospital billing system provided cost
      estimates. Quality-adjusted life years (QALYs) were calculated using health
      related quality of life data from the European Organization for Research and
      Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C-30)
      translated into the Euro Quality of Life- 5-Dimensional classification. On the
      basis of the medical cost offset, a cost-utility analysis was performed. RESULTS:
      Health care utilization was mainly related to the breast cancer diagnosis and
      treatment. The intervention costs amounted to about ?500 or 3% of the total
      costs. Total health care costs, including interventions cost, were lower in the
      INS (?18,670) and IPS (?20,419) groups than in the SC group (?25,800). The number
      of QALYs were also higher in the INS (1.52 QALY) and IPS (1.59 QALY) groups,
      compared with the SC group (1.43 QALY). CONCLUSIONS: The cost-utility analysis
      revealed that, during adjuvant treatment for breast cancer, the individual
      psychosocial support interventions provided here was cost effective because the
      health care costs were lower and QALYs were higher compared to SC alone.

PMID- 24115470
TI  - An in vitro skin model to study the effect of mesenchymal stem cells in wound
      healing and epidermal regeneration.
AB  - The development of new wound therapies, such as bioengineered skin equivalents,
      is an ongoing process. Multi-potent mesenchymal stem cells (MSCs) give rise to
      many tissue lineages and have been implicated in wound healing making them a
      potential candidate for cell-based bioengineered products for injured tissue. In
      this study, we investigated the mesenchymal/epithelial interactions of cultured
      MSCs in comparison to cultured fibroblasts on epidermal proliferation,
      differentiation, and extracellular matrix (ECM) protein expression using a de
      epidermalized dermis (DED) skin model. We also studied whether MSCs can
      transdifferentiate to keratinocytes using the same model. Keratinocytes were
      cultured on unseeded DED or DED populated with fibroblasts or MSCs at an air
      liquid interface to induce epidermal differentiation. Fibroblasts or MSCs were
      also seeded on the papillary surface of the DED alone or on the reticular
      surface. General histology and immunostaining was performed on the skin
      equivalents to examine the expression of pan keratin (K) (K1, K5, K6, and K18)
      and protein markers for epidermal differentiation (K10), hyperproliferation (K6),
      proliferation (PCNA), ECM component (collagen type IV), and mesenchymal marker
      (vimentin). Keratinocyte-fibroblast skin model and keratinocyte-MSC skin model
      both displayed an epidermal phenotype similar to epidermis in vivo. Positive
      expression of proliferation, differentiation and ECM protein markers was
      observed. MSCs failed to adopt an epithelial phenotype in the DED skin model. Our
      findings highlight the potential use of MSCs in bioengineered tissue for the
      treatment of wounds.

PMID- 24115471
TI  - Iridium and rhodium complexes within a macroreticular acidic resin: a
      heterogeneous photocatalyst for visible-light driven H2 production without an
      electron mediator.
AB  - Direct ion exchange of cyclometalated iridium(III) and tris-2,2'-bipyridyl
      rhodium(III) complexes, of which the former acts as a photosensitizer and the
      latter as a proton reduction catalyst, within a macroreticular acidic resin has
      been accomplished with the aim of developing a photocatalyst for H2 production
      under visible-light irradiation. Ir L(III)-edge and Rh K-edge X-ray absorption
      fine structure (XAFS) measurements suggest that the Ir and Rh complexes are
      easily accommodated in the macroreticular space without considerable structural
      changes. The photoluminescence emission of the exchanged Ir complex due to a
      triplet ligand charge-transfer ((3)LC) and metal-to-ligand charge-transfer
      ((3)MLCT) transition near 550 nm decreases with increasing the amount of the Rh
      complex, thus suggesting the occurrence of an electron transfer from Ir to Rh.
      The Ir-Rh/resin catalyst behaves as a heterogeneous photocatalyst capable of both
      visible-light sensitization and H2 production in an aqueous medium in the absence
      of an electron mediator. The photocatalytic activitity is strongly dependent on
      the amount of the components and reaches a maximum at a molar ratio of 2:1 of
      Ir/Rh complexes. Moreover, leaching and agglomeration of the active metal
      complexes are not observed, and the recovered photocatalyst can be recycled
      without loss in catalytic activity.

PMID- 24115472
TI  - Deep brain stimulation for anorexia nervosa: a step forward.

PMID- 24115473
TI  - A single mutation at the ferredoxin binding site of P450 Vdh enables efficient
      biocatalytic production of 25-hydroxyvitamin D(3).
AB  - Vitamin D3 hydroxylase (Vdh) from Pseudonocardia autotrophica is a cytochrome
      P450 monooxygenase that catalyzes the two-step hydroxylation of vitamin D3 (VD3 )
      to produce 25-hydroxyvitamin D3 (25(OH)VD3 ) and 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2 VD3 ). These hydroxylated forms of VD3 are useful as
      pharmaceuticals for the treatment of conditions associated with VD3 deficiency
      and VD3 metabolic disorder. Herein, we describe the creation of a highly active
      T107A mutant of Vdh by engineering the putative ferredoxin-binding site.
      Crystallographic and kinetic analyses indicate that the T107A mutation results in
      conformational change from an open to a closed state, thereby increasing the
      binding affinity with ferredoxin. We also report the efficient biocatalytic
      synthesis of 25(OH)VD3 , a promising intermediate for the synthesis of various
      hydroxylated VD3 derivatives, by using nisin-treated Rhodococcus erythropolis
      cells containing VdhT107A . The gene-expression cassette encoding Bacillus
      megaterium glucose dehydrogenase-IV was inserted into the R. erythropolis
      chromosome and expressed to avoid exhaustion of NADH in a cytoplasm during
      bioconversion. As a result, approximately 573 MUg mL(-1) 25(OH)VD3 was
      successfully produced by a 2 h bioconversion.

PMID- 24115474
TI  - The vasculature in diabetic nephropathy: all tied up?

PMID- 24115475
TI  - Obesity in CKD--what should nephrologists know?
AB  - Obesity, the epidemic of the 21st century, carries a markedly increased risk for
      comorbid complications, such as type 2 diabetes, cancer, hypertension,
      dyslipidemia, cardiovascular disease, and sleep apnea. In addition, obesity
      increases the risk for CKD and its progression to ESRD. Paradoxically, even
      morbid obesity associates with better outcomes in studies of ESRD patients on
      maintenance dialysis. Because the number of obese CKD and maintenance dialysis
      patients is projected to increase markedly in developed as well as low- and
      middle-income countries, obesity is a rapidly emerging problem for the
      international renal community. Targeting the obesity epidemic represents an
      unprecedented opportunity for health officials to ameliorate the current
      worldwide increase in CKD prevalence. Nephrologists need more information about
      assessing and managing obesity in the setting of CKD. Specifically, more precise
      estimation of regional fat distribution and the amount of muscle mass should be
      introduced into regular clinical practice to complement more commonly used
      practical markers, such as body mass index. Studies examining the effects of
      obesity on kidney disease progression and other clinical outcomes along with
      weight management strategies are much needed in this orphan area of research. 

PMID- 24115476
TI  - A pegylated leptin antagonist ameliorates CKD-associated cachexia in mice.
AB  - Elevated serum leptin levels correlate with inflammation and predict changes in
      lean body mass in patients with CKD, and activation of the melanocortin system by
      leptin signaling mediates the pathophysiology of CKD-associated cachexia. We
      tested whether treatment with a pegylated leptin receptor antagonist (PLA)
      attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA
      (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels
      in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain,
      improved lean mass and muscle function, reduced energy expenditure, and
      normalized the levels of hepatic TNF-alpha and IL-6 mRNA in mice with CKD.
      Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated
      increase in the transcriptional and protein abundance of uncoupling proteins that
      mediates thermogenesis, and it normalized the molecular signatures of processes
      associated with muscle wasting in CKD, including proteolysis, myogenesis and
      muscle regeneration, and expression of proinflammatory muscle cytokines, such as
      IL-1alpha, -1beta, and -6 and TNF-alpha. Our results suggest that leptin
      antagonism may represent a viable therapeutic strategy for cachexia in CKD. 

PMID- 24115477
TI  - UNC5B receptor deletion exacerbates tissue injury in response to AKI.
AB  - Netrin-1 regulates cell survival and apoptosis by activation of its receptors,
      including UNC5B. However, the in vivo role of UNC5B in cell survival during
      cellular stress and tissue injury is unknown. We investigated the role of UNC5B
      in cell survival in response to stress using mice heterozygously expressing the
      UNC5B gene (UNC5B(-/flox)) and mice with targeted homozygous deletion of UNC5B in
      kidney epithelial cells (UNC5B(-/flox/GGT-cre)). Mice were subjected to two
      different models of organ injury: ischemia reperfusion injury of the kidney and
      cisplatin-induced nephrotoxicity. Both mouse models of UNC5B depletion had normal
      organ function and histology under basal conditions. After AKI, however, UNC5B(
      /flox/GGT-cre) mice exhibited significantly worse renal function and damage,
      increased tubular apoptosis, enhanced p53 activation, and exacerbated
      inflammation compared with UNC5B(-/flox) and wild-type mice. shRNA-mediated
      suppression of UNC5B expression in cultured tubular epithelial cells exacerbated
      cisplatin-induced cell death in a p53-dependent manner and blunted Akt
      phosphorylation. Inhibition of PI3 kinase similarly exacerbated cisplatin-induced
      apoptosis; in contrast, overexpression of UNC5B reduced cisplatin-induced
      apoptosis in these cells. Taken together, these results show that the netrin-1
      receptor UNC5B plays a critical role in cell survival and kidney injury through
      Akt-mediated inactivation of p53 in response to stress. 

PMID- 24115478
TI  - Psychosocial intervention improves depression, quality of life, and fluid
      adherence in hemodialysis.
AB  - Patients with ESRD have high rates of depression, which is associated with
      diminished quality of life and survival. We determined whether individual
      cognitive behavioral therapy (CBT) reduces depression in hemodialysis patients
      with elevated depressive affect in a randomized crossover trial. Of 65
      participants enrolled from two dialysis centers in New York, 59 completed the
      study and were assigned to the treatment-first group (n=33) or the wait-list
      control group (n=26). In the intervention phase, CBT was administered chairside
      during dialysis treatments for 3 months; participants were assessed 3 and 6
      months after randomization. Compared with the wait-list group, the treatment
      first group achieved significantly larger reductions in Beck Depression Inventory
      II (self-reported, P=0.03) and Hamilton Depression Rating Scale (clinician
      reported, P<0.001) scores after intervention. Mean scores for the treatment-first
      group did not change significantly at the 3-month follow-up. Among participants
      with depression diagnosed at baseline, 89% in the treatment-first group were not
      depressed at the end of treatment compared with 38% in the wait-list group
      (Fisher's exact test, P=0.01). Furthermore, the treatment-first group experienced
      greater improvements in quality of life, assessed with the Kidney Disease Quality
      of Life Short Form (P=0.04), and interdialytic weight gain (P=0.002) than the
      wait-list group, although no effect on compliance was evident at follow-up. In
      summary, CBT led to significant improvements in depression, quality of life, and
      prescription compliance in this trial, and studies should be undertaken to assess
      the long-term effects of CBT on morbidity and mortality in patients with ESRD. 

PMID- 24115479
TI  - Prevention and management of non-communicable disease: the IOC consensus
      statement, Lausanne 2013.
AB  - Morbidity and mortality from preventable, non-communicable chronic disease (NCD)
      threatens the health of our populations and our economies. The accumulation of
      vast amounts of scientific knowledge has done little to change this. New and
      innovative thinking is essential to foster new creative approaches that leverage
      and integrate evidence through the support of big data, technology and design
      thinking. The purpose of this paper is to summarise the results of a consensus
      meeting on NCD prevention sponsored by the IOC in April 2013. Within the context
      of advocacy for multifaceted systems change, the IOC's focus is to create
      solutions that gain traction within healthcare systems. The group of participants
      attending the meeting achieved consensus on a strategy for the prevention and
      management of chronic disease that includes the following: (1) Focus on
      behavioural change as the core component of all clinical programmes for the
      prevention and management of chronic disease. (2) Establish actual centres to
      design, implement, study and improve preventive programmes for chronic disease.
      (3) Use human-centred design in the creation of prevention programmes with an
      inclination to action, rapid prototyping and multiple iterations. (4) Extend the
      knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build
      new programmes for the prevention and treatment of chronic disease focused on
      physical activity, diet and lifestyle. (5) Mobilise resources and leverage
      networks to scale and distribute programmes of prevention. True innovation lies
      in the ability to align thinking around these core strategies to ensure
      successful implementation of NCD prevention and management programmes within
      healthcare. The IOC and SEM community are in an ideal position to lead this
      disruptive change. The outcome of the consensus meeting was the creation of the
      IOC Non-Communicable Diseases ad hoc Working Group charged with the
      responsibility of moving this agenda forward. 

PMID- 24115480
TI  - How to minimise the health risks to athletes who compete in weight-sensitive
      sports review and position statement on behalf of the Ad Hoc Research Working
      Group on Body Composition, Health and Performance, under the auspices of the IOC
      Medical Commission.
AB  - A focus on low body weight and body fat content, combined with regulations in
      some weight-sensitive sports, are considered risk factors for extreme dieting,
      eating disorders (EDs) and related health consequences among athletes. At present
      there are, from a health perspective, no generally accepted optimum values for
      body weight or percentage of fat mass in different sports and there is no 'gold
      standard' method for body composition assessment in athletes. On the basis of
      health considerations as well as performance, medical support teams should know
      how to approach elite athletes who seek to achieve an unrealistic body
      composition and how to prevent restrictive eating practices from developing into
      an ED. In addition, these teams must know when to raise the alarm and how to
      advice athletes who are affected by extreme dieting or clinical EDs. However,
      there is no consensus on when athletes struggling with extreme dieting or EDs
      should be referred for specialist medical treatment or removed from competition.
      Based on the present review, we conclude that there is a need for (1) sport
      specific and gender-specific preventive programmes, (2) criteria for raising
      alarm and 'does not start' (DNS) for athletes with EDs and (3) modifications to
      the regulations in some sports. Further, the key areas for research identified
      include the development of standard methods for body composition assessment in
      elite athletes; screening measures for EDs among athletes; development and
      testing of prevention programmes; investigating the short and long-term effects
      of extreme dieting; and EDs on health and performance. 

PMID- 24115481
TI  - Nesting and acoustic ecology, but not phylogeny, influence passerine urban
      tolerance.
AB  - Urbanization is one of the most extensive and ecologically significant changes
      happening to terrestrial environments, as it strongly affects the distribution of
      biodiversity. It is well established that native species richness is reduced in
      urban and suburban areas, but the species traits that predict tolerance to
      urbanization are yet little understood. In birds, one of the most studied groups
      in this respect, evidence is appearing that acoustic traits influence urban
      living, but it remains unknown how this compares to the effects of more obvious
      ecological traits that facilitate urban living. Therefore, it remains unclear
      whether acoustic communication is an important predictor of urban tolerance among
      species. Here, with a comparative study across 140 European and North American
      passerines, I show that high song frequency, which is less masked by the low
      frequency anthropogenic noise, is associated with urban tolerance, with an effect
      size over half that of the most important ecological trait studied: off-ground
      nesting. Other nesting and foraging traits accepted to facilitate urban living
      did not differ for species occurring in urban environments. Thus, the
      contribution of acoustic traits for passerine urban tolerance approximates that
      of more obvious ecological traits. Nonetheless, effect sizes of the biological
      predictors of urban tolerance were low and the phylogenetic signal for urban
      tolerance was null, both of which suggest that factors other than phenotypic
      traits have major effects on urban tolerance. A simple possibility is exposure to
      urbanization, as there was a higher proportion of urban-tolerant species in
      Europe, which is more urbanized than North America. 

PMID- 24115482
TI  - A patient with a unique frameshift mutation in GPC3, causing Simpson-Golabi
      Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a
      large prostatic utricle.
AB  - We present a Hispanic male with the clinical and molecular diagnosis of Simpson
      Golabi-Behmel syndrome (SGBS). The patient was born with multiple anomalies not
      entirely typical of SGBS patients, including penoscrotal hypospadias, a large
      prostatic utricle, and left coronal craniosynostosis. In addition, he
      demonstrated endocrine anomalies including a low random cortisol level suspicious
      for adrenal insufficiency and low testosterone level. To our knowledge, this is
      the first report of a prostatic utricle in SGBS and the second report of
      craniosynostosis. The unique disease-causing mutation likely arose de novo in the
      mother. It is a deletion-insertion that leads to a frameshift at the p.p. S359
      [corrected] residue of GPC3 and a premature stop codon after five more amino
      acids. p. S359 [corrected] is the same residue that is normally cleaved by the
      Furin convertase, although the significance of this novel mutation with respect
      to the patient's multiple anomalies is unknown. We present this case as the
      perinatal course of a patient with unique features of SGBS and a confirmed
      molecular diagnosis.

PMID- 24115483
TI  - Biomimetic synthesis of an ultrathin platinum nanowire network with a high twin
      density for enhanced electrocatalytic activity and durability.

PMID- 24115484
TI  - Thiol-click chemistries for responsive neural interfaces.
AB  - Neural interfaces provide an electrical connection between computers and the
      nervous system: current penetrating devices are orders-of-magnitude stiffer than
      surrounding tissue. In this work, recent efforts in softening electronics and
      utilize thiol-ene and thiol-epoxy "click" reactions are built upon to incorporate
      fluid-sensitive hydrogen bonding into smart substrates for high electrode density
      neural interfaces. The modulus of these substrates drops more than two orders of
      magnitude in response to physiological conditions, despite fluid uptake of less
      than 6%, and can be tuned by the covalent crosslink density and degree of
      hydrogen bonding in the polymer network. Intracortical and intrafascicular
      electrode arrays are fabricated and characterized with impedance spectroscopy and
      cyclic voltammetry. 

PMID- 24115485
TI  - Comparison of the effect of insecticides on three strains of Tyrophagus
      putrescentiae (Acari: Astigmata) using an impregnated filter paper test and a
      growth test.
AB  - BACKGROUND: In this study, we compared the efficacy of insecticides against three
      strains of Tyrophagus putrescentiae using an impregnated filter paper test and a
      growth test. We tested the suppressive activity of commercial insecticides and
      their analytical standards (pirimiphos-methyl, cypermethrin, deltamethrin,
      chlorfenapyr, beta-cyfluthrin). METHODS: The strains of T. putrescentiae
      originated from a laboratory, a field and dog food. The mortality of the mites
      due to active ingredients and analytical standards was tested using an
      impregnated filter paper test after 24 h. Lethal doses, LD50 , LD95 and LD99 were
      determined. A growth test was used to observe the suppressive effect of the
      active ingredients on mites at 21 days after application of the active
      ingredients to wheat grain. The effective doses ED50 , ED95 and ED99 were
      determined, indicating the concentration at which the population was reduced by
      50, 95 and 99% more than control. RESULTS: Cypermethrin, beta-cyfluthrin and a
      formulation of deltamethrin with piperonylbutoxide in the pesticide K-Othrine
      showed low toxicity to mites. High toxicity was observed for chlorfenapyr (LD50 :
      0.1-1 ug cm(-2) ; ED50 : 0.11-1.2 ug g(-1) ) and pirimiphos-methyl (LD50 : 0.01
      0.06 ug cm(-2) ; ED50 : 0.2-12 ug g(-1) ). We did not find significant
      differences among the compared strains in terms of their sensitivity to highly
      toxic insecticides. CONCLUSION: The obtained results showed that a filter paper
      test is a more sensitive method of identifying differences in pesticide
      susceptibility among strains, but the efficacy of pesticides against one species
      should be tested using a growth test.

PMID- 24115486
TI  - Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function
      against oxidative stress.
AB  - SCOPE: Diabetes mellitus is associated with reductions in glutathione, supporting
      the critical role of oxidative stress in its pathogenesis. Antioxidant food
      components such as flavonoids have a protective role against oxidative stress
      induced degenerative and age-related diseases. Flavonoids such as epicatechin
      (EC) constitute an important part of the human diet; they can be found in green
      tea, grapes, and cocoa and possess multiple biological activities. This study
      investigates the chemo-protective effect of EC against oxidative stress induced
      by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. METHODS AND
      RESULTS: Cell viability, oxidative status, phosphorylated Jun kinase (p-JNK)
      expression, and insulin secretion were evaluated. Ins-1E cells treatment with 5
      20 MUM EC for 20 h evoked no cell damage and enhanced antioxidant enzymes and
      insulin secretion. Addition of 50 MUM t-BOOH for 2 h induced reactive oxygen
      species, p-JNK, and carbonyl groups and decreased GSH and insulin secretion.
      Pretreatment of cells with EC prevented the t-BOOH-induced reactive oxygen
      species, carbonyl groups, p-JNK expression and cell death, and recovered insulin
      secretion. CONCLUSION: Ins-1E cells treated with EC showed a remarkable recovery
      of cell viability and insulin secretion damaged by t-BOOH, indicating that
      integrity of secreting and surviving machineries in the EC-treated cells was
      notably protected against the oxidative insult.

PMID- 24115487
TI  - "What does not kill me makes me stronger": is it always true?

PMID- 24115488
TI  - A ball-joint-type host-guest system that consists of conglomerate helical
      metallacyclophanes.

PMID- 24115489
TI  - Patterns of change in different phases of outpatient psychotherapy: a stage
      sequential pattern analysis of change in session reports.
AB  - Knowledge about typical change patterns of psychotherapy patients can help to
      improve treatment guidelines for psychological disorders. Recent studies showed
      that it is possible to identify several patient subgroups with regard to their
      early change pattern. However, although focusing on the early phase of treatment,
      change patterns in later stages have hardly been investigated yet. In this study,
      Growth Mixture Modelling was used to identify latent change classes in different
      phases of therapy in a naturalistic sample of 1229 psychotherapy outpatients.
      Furthermore, this paper inquired into the relation between the change patterns in
      different phases as well as their predictive power for therapy length and
      outcome. Results revealed different change patterns for the three investigated
      phases. While in an early treatment phase, (sessions one-six) five different
      change patterns could be identified: the number of change classes decreased
      considerably over time, resulting in three patterns in the second (sessions 7-12)
      and two in the third phase (sessions 13-18). In each phase, by far, the biggest
      class showed a pattern of good progress with small/no further improvements. KEY
      PRACTITIONER MESSAGES: Most change in patients' progress estimates took place in
      an early phase of the treatment and levelled out on a relatively high level in
      later phases of the treatment. Substantial improvements were still present in
      later phases of the treatment but occurred less frequent than in early stages.
      Continuous outcome monitoring and feedback systems should integrate progress
      measures to monitor patients progress especially in the early phase of the
      treatment and feed the so gained information back to therapists.

PMID- 24115490
TI  - Quantitative assessment of fat infiltration in the rotator cuff muscles using
      water-fat MRI.
AB  - PURPOSE: To evaluate a chemical shift-based fat quantification technique in the
      rotator cuff muscles in comparison with the semiquantitative Goutallier fat
      infiltration classification (GC) and to assess their relationship with clinical
      parameters. MATERIALS AND METHODS: The shoulders of 57 patients were imaged using
      a 3T MR scanner. The rotator cuff muscles were assessed for fat infiltration
      using GC by two radiologists and an orthopedic surgeon. Sequences included
      oblique-sagittal T1-, T2-, and proton density-weighted fast spin echo, and six
      echo gradient echo. The iterative decomposition of water and fat with echo
      asymmetry and least-squares estimation (IDEAL) was used to measure fat fraction.
      Pain and range of motion of the shoulder were recorded. RESULTS: Fat fraction
      values were significantly correlated with GC grades (P < 0.0001, kappa >0.9)
      showing consistent increase with GC grades (grade = 0, 0%-5.59%; grade = 1, 1.1%
      9.70%; grade = 2, 6.44%-14.86%; grade = 3, 15.25%-17.77%; grade = 4, 19.85%
      29.63%). A significant correlation between fat infiltration of the subscapularis
      muscle quantified with IDEAL versus 1) deficit in internal rotation (Spearman
      Rank Correlation Coefficient [SRC] = 0.39, 95% confidence interval [CI] 0.13
      0.60, P < 0.01) and 2) pain (SRC coefficient = 0.313, 95% CI 0.049-0.536, P =
      0.02) was found but was not seen between the clinical parameters and GC grades.
      Additionally, only quantitative fat infiltration measures of the supraspinatus
      muscle were significantly correlated with a deficit in abduction (SRC coefficient
      = 0.45, 95% CI 0.20-0.60, P < 0.01). CONCLUSION: An accurate and highly
      reproducible fat quantification in the rotator cuff muscles using water-fat
      magnetic resonance imaging (MRI) techniques is possible and significantly
      correlates with shoulder pain and range of motion.

PMID- 24115491
TI  - Gene expression profile study on osteoinductive effect of natural hydroxyapatite.
AB  - The aim of this study was to investigate the osteoinductive effect of natural
      hydroxyapatite (NHA). NHA was extracted from pig bones and prepared into disk
      like samples. Then, proliferation of mouse bone mesenchymal stem cells (MSCs)
      cultured on NHA was assessed by the methylthiazoltetrazolium (MTT) assay.
      Furthermore, microarray technology was applied to obtain the gene expression
      profiles of MSCs cultured on NHA at 24, 48, and 72 h. The gene expression profile
      was then comprehensively analyzed by clustering, Gene Ontology (GO), Gene
      Microarray Pathway Profiler (GenMAPP) and Ingenuity Pathway Analysis (IPA).
      According to the results of microarray experiment, 8992 differentially expressed
      genes were obtained. 90 differential expressed genes related to HA osteogenic
      differentiation were determined by GO analysis. These genes included not only 6
      genes related to HA osteogenic differentiation as mentioned in the literatures
      but also newly discovered 84 genes. Some important signaling pathways (TGF-beta,
      MAPK, Wnt, etc.) were influenced by these genes. Gene interaction networks were
      obtained by IPA software, in which the scoring values of two networks were
      highest, and their main functions were related to cell development. The
      comprehensive analysis of these results indicate that NHA regulate some crucial
      genes (e.g., Bmp2, Spp1) and then activate some pathways such as TGF-beta
      signaling pathway, and ultimately osteogenic differentiation was induced.

PMID- 24115492
TI  - Toward GPGPU accelerated human electromechanical cardiac simulations.
AB  - In this paper, we look at the acceleration of weakly coupled electromechanics
      using the graphics processing unit (GPU). Specifically, we port to the GPU a
      number of components of CHeart--a CPU-based finite element code developed for
      simulating multi-physics problems. On the basis of a criterion of computational
      cost, we implemented on the GPU the ODE and PDE solution steps for the
      electrophysiology problem and the Jacobian and residual evaluation for the
      mechanics problem. Performance of the GPU implementation is then compared with
      single core CPU (SC) execution as well as multi-core CPU (MC) computations with
      equivalent theoretical performance. Results show that for a human scale left
      ventricle mesh, GPU acceleration of the electrophysiology problem provided
      speedups of 164 * compared with SC and 5.5 times compared with MC for the
      solution of the ODE model. Speedup of up to 72 * compared with SC and 2.6 *
      compared with MC was also observed for the PDE solve. Using the same human
      geometry, the GPU implementation of mechanics residual/Jacobian computation
      provided speedups of up to 44 * compared with SC and 2.0 * compared with MC.

PMID- 24115493
TI  - Performance of zwitterionic hydrophilic interaction LC for the determination of
      iodinated X-ray contrast agents.
AB  - This study compares the separation performance of a group of iodinated X-ray
      contrast media on four different columns. The first three were two stationary
      phases (SPs) modified with C18 and a polar-embedded SP (polar amide group bonded
      to an alkyl chain), all of which worked under RP-LC mode. The fourth was a
      zwitterionic sulphoalkylbetaine SP, working under the hydrophilic interaction LC
      (HILIC) mode. After the optimisation of the different parameters, the
      zwitterionic column displayed the best separation, which also overcomes the
      problems encountered when these analytes were separated under RP-LC. Moreover,
      when HILIC is coupled to MS/MS, sensitivity is enhanced. However, when sewage
      samples were analysed by SPE followed by the optimal HILIC-MS/MS, the sensitivity
      of the method was affected due to the high matrix effect, which had to be solved
      by dilution of the extract. Finally, the method was preliminarily validated with
      sewage and the figures of merit were comparable to those of the SPE-RP-LC-MS/MS. 

PMID- 24115494
TI  - A "dial-a-receptor" dynamic combinatorial library.
AB  - Making receptors to order: A small dynamic combinatorial library (DCL), formed
      from two dithiols in water, provides a continuous range of six receptors of
      different sizes. The majority of the 30 tested amines and ammonium ions amplified
      receptors from this library, thus spanning the complete receptor-size range and
      showing that this DCL provides a generic platform for the development of
      receptors for this important class of compounds. 

PMID- 24115495
TI  - Thermodynamic phase transition through crystal-to-crystal process of photochromic
      1,2-bis(5-phenyl-2-propyl-3-thienyl)perfluorocyclopentene.
AB  - A photochromic diarylethene, 1,2-bis(5-phenyl-2-propyl-3
      thienyl)perfluorocyclopentene (1a), was found to have two polymorphic crystal
      forms, alpha- and beta-crystals. From X-ray crystallographic analysis, the space
      groups of alpha- and beta-crystals were determined to be P21 /c and C2/c,
      respectively. The difference between two crystal forms is ascribed to the
      orientation of two of four molecules in the unit cell. The thermodynamic phase
      transition from alpha- to beta-forms occurred via a crystal-to-crystal process,
      as confirmed by differential scanning calorimetry measurements, optical
      microscopic observations in the reflection mode and under crossed Nicols, and
      powder X-ray diffraction measurements. The movement of the molecules in the
      crystal was evaluated by analyzing the change of face indices before and after
      the phase transition.

PMID- 24115496
TI  - Managing leaf-cutting ants: peculiarities, trends and challenges.
AB  - Leaf-cutting ants are generally recognized as important pest species in
      Neotropical America. They are eusocial insects that exhibit social organization,
      foraging, fungus-cultivation, hygiene and a complex nest structure, which render
      their management notoriously difficult. A lack of economic thresholds and
      sampling plans focused on the main pest species preclude the management of leaf
      cutting ants; such management would facilitate their control and lessen
      insecticide overuse, particularly the use of insecticidal baits. Recent
      restrictions on the use of synthetic compounds for such purposes impose
      additional challenges for the management of leaf-cutting ants. Considerable
      effort has been exerted regarding these challenges, which are addressed herein,
      but which also remain challenges that are yet to be conquered.

PMID- 24115497
TI  - Accumulation of promutagenic DNA adducts in the mouse distal colon after
      consumption of heme does not induce colonic neoplasms in the western diet model
      of spontaneous colorectal cancer.
AB  - SCOPE: Red meat is considered a risk factor for colorectal cancer (CRC). Heme is
      considered to promote colonic hyperproliferation and cell damage. Resistant
      starch (RS) is a food that ferments in the colon with studies demonstrating
      protective effects against CRC. By utilizing the western diet model of
      spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to
      a high red meat diet would increase colonic DNA adducts and CRC and whether RS
      could abrogate such effects. METHODS AND RESULTS: Four groups of mice: control,
      heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed
      for apoptosis, proliferation, DNA adducts "8-hydroxy-2-deoxyguanosine" and "O(6) 
      methyl-2-deoxyguanosine" (O(6) MeG), and neoplasms. In the short term, heme
      increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed
      increased cell proliferation (p < 0.01) and 8-hydroxy-2-deoxyguanosine adducts (p
      < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01)
      and increased O(6) MeG adducts (p < 0.01). The incidence of colon neoplasms was
      not different between any interventions. CONCLUSION: We identified heme to
      increase proliferation in the short term, inhibit apoptosis over the long term,
      and increase O(6) MeG adducts in the colon over time although these changes did
      not affect colonic neoplasms within this mouse model.

PMID- 24115498
TI  - Enhancement of all-trans retinoic acid-induced differentiation by pH-sensitive
      nanoparticles for solid tumor cells.
AB  - Cancer differentiation therapy is an attractive concept and has been clinically
      used to treat leukemia. However, it is limited to date for solid tumors. In this
      study, the pH-sensitive nanoparticles based on poly(amidoamine) (PAMAM)
      dendrimers are synthesized by coupling 3,4,5,6-tetrahydrophthalic anhydride with
      the first generation PAMAM. The modified dendrimers can self-assemble in aqueous
      solution to form nanoparticles with a diameter of 125-435 nm. The nanoparticles
      are relatively stable at physiological pH (pH 7.4) but dissociated in acidic
      environments (pH 5.0 or 6.0). The present studies show that the proliferation
      inhibition and albumin secretion of hepatoma carcinoma cells are enhanced with
      all-trans retinoic acid (ATRA) encapsulated in the nanoparticles. The enhancement
      of induced differentiation is due to the high internalization of ATRA in the
      cells by the nanoparticles. These experimental results demonstrate that pH
      sensitive nanoparticles may be efficient for improving the differentiation
      therapy for solid tumor.

PMID- 24115499
TI  - How do researchers conceive of spousal grief after cancer? A systematic review of
      models used by researchers to study spousal grief in the cancer context.
AB  - BACKGROUND: Although spouses bereaved after cancer are considered vulnerable
      people, there have been few empirical studies to explore grief specifically in
      this context. METHODS: Using PsycINFO, Medline, and the PRISMA statement, we
      systematically searched the literature by intersecting 'cancer' and 'grie*',
      'cancer' and 'bereave*', and 'cancer' and 'mourn*'. RESULTS: Gathering 76 studies
      (2000-2013) that met the inclusion criteria for bereavement in adulthood,
      bereavement of an adult loved one and evidence-based research, we found the
      following: Spousal relationships are not systematically examined in the current
      dominant models of grief. Theoretically derived determinants of spousal grief
      after cancer and empirically derived ones converge toward the necessity to
      include the caregiving experience as determining grief reactions. A growing body
      of literature concerning prolonged grief disorders now provides integrative
      reflections regarding the characteristics of spousal loss, predictors, and
      associated therapeutic interventions in the cancer context. CONCLUSIONS: Few
      empirical studies (20 of 76) target spousal bereavement specifically after
      cancer. The process of adaptation to loss is usually decontextualized, removing
      any consideration of the relationship to the deceased or the experience of
      caregiving and dying. Our findings suggest that this topic warrants more studies
      that use both prospective and mixed methodologies, as well as explore typical
      grief needs and experiences of bereaved spouses.

PMID- 24115500
TI  - Metal/N-heterocyclic carbene complexes: opportunities for the development of
      anticancer metallodrugs.

PMID- 24115501
TI  - Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to
      the group of FRAS-FREM complex disorders.
AB  - Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare
      congenital malformation syndrome. It overlaps clinically with Fraser syndrome
      (FS; OMIM 219000), which is known to be caused by mutations in either FRAS1,
      FREM2, or GRIP1, encoding components of a protein complex that plays a role in
      epidermal-dermal interactions during morphogenetic processes. We explored the
      hypothesis that AMS might be either allelic to FS or caused by mutations in other
      genes encoding known FRAS1 interacting partners. No mutation in either of these
      genes was found in a cohort of 11 patients with AMS from 10 unrelated families.
      These findings demonstrate that AMS is genetically distinct from FS. It is
      proposed that it constitutes a separate entity within the group of FRAS-FREM
      complex disorders.

PMID- 24115502
TI  - Fabrication and characterization of biomimetic multichanneled crosslinked
      urethane-doped polyester tissue engineered nerve guides.
AB  - Biomimetic scaffolds that replicate the native architecture and mechanical
      properties of target tissues have been recently shown to be a very promising
      strategy to guide cellular growth and facilitate tissue regeneration. In this
      study, porous, soft, and elastic crosslinked urethane-doped polyester (CUPE)
      tissue engineered nerve guides were fabricated with multiple longitudinally
      oriented channels and an external non-porous sheath to mimic the native
      endoneurial microtubular and epineurium structure, respectively. The fabrication
      technique described herein is highly adaptable and allows for fine control over
      the resulting nerve guide architecture in terms of channel number, channel
      diameter, porosity, and mechanical properties. Biomimetic multichanneled CUPE
      guides were fabricated with various channel numbers and displayed an ultimate
      peak stress of 1.38 +/- 0.22 MPa with a corresponding elongation at break of
      122.76 +/- 42.17%, which were comparable to that of native nerve tissue. The CUPE
      nerve guides were also evaluated in vivo for the repair of a 1 cm rat sciatic
      nerve defect. Although histological evaluations revealed collapse of the inner
      structure from CUPE TENGs, the CUPE nerve guides displayed fiber populations and
      densities comparable with nerve autograft controls after 8 weeks of implantation.
      These studies are the first report of a CUPE-based biomimetic multichanneled
      nerve guide and warrant future studies towards optimization of the channel
      geometry for use in neural tissue engineering.

PMID- 24115504
TI  - Long-term response of a Mojave Desert winter annual plant community to a whole
      ecosystem atmospheric CO2 manipulation (FACE).
AB  - Desert annuals are a critically important component of desert communities and may
      be particularly responsive to increasing atmospheric (CO2 ) because of their high
      potential growth rates and flexible phenology. During the 10-year life of the
      Nevada Desert FACE (free-air CO2 enrichment) Facility, we evaluated the
      productivity, reproductive allocation, and community structure of annuals in
      response to long-term elevated (CO2 ) exposure. The dominant forb and grass
      species exhibited accelerated phenology, increased size, and higher reproduction
      at elevated (CO2 ) in a wet El Nino year near the beginning of the experiment.
      However, a multiyear dry cycle resulted in no increases in productivity or
      reproductive allocation for the remainder of the experiment. At the community
      level, early indications of increased dominance of the invasive Bromus rubens at
      elevated (CO2 ) gave way to an absence of Bromus in the community during a
      drought cycle, with a resurgence late in the experiment in response to higher
      rainfall and a corresponding high density of Bromus in a final soil seed bank
      analysis, particularly at elevated (CO2 ). This long-term experiment resulted in
      two primary conclusions: (i) elevated (CO2 ) does not increase productivity of
      annuals in most years; and (ii) relative stimulation of invasive grasses will
      likely depend on future precipitation, with a wetter climate favoring invasive
      grasses but currently predicted greater aridity favoring native dicots. 

PMID- 24115503
TI  - Vicinal disulfide constrained cyclic peptidomimetics: a turn mimetic scaffold
      targeting the norepinephrine transporter.

PMID- 24115505
TI  - Visualization of acute focal lesions in rats with experimental autoimmune
      encephalomyelitis by magnetic nanoparticles, comparing different MRI sequences
      including phase imaging.
AB  - PURPOSE: To compare the sensitivity and specificity of phase imaging (PI) with
      other magnetic resonance imaging (MRI) methods in lesion detection in rats with
      experimental autoimmune encephalomyelitis (EAE), as an animal model for multiple
      sclerosis (MS). MATERIALS AND METHODS: EAE was induced in rats (n = 14) by
      subcutaneous (s.c.) injection of myelin basic protein (MBP) and complete Freund's
      adjuvant (CFA). Control animals (n = 4) were given an s.c. injection of phosphate
      buffered saline mixed with CFA. The development of local inflammatory processes,
      demyelinations, and blood-brain barrier (BBB) disruptions were monitored over 7
      weeks in a 4.7T animal scanner by T1-, T2-, T2*-weighted images, magnetization
      transfer, and PI in the presence or absence of very small superparamagnetic iron
      oxide particles (VSOP) and confirmed by immunostaining using CD31, CD68, MBP, and
      albumin antibodies and Gallyas silver staining. RESULTS: EAE rats developed time
      dependent local inflammations and BBB disruptions but no clear demyelinizations.
      In histological stainings these processes were trackable as accumulations of
      phagocytic monocytes and extravasal albumin. In MRI without application of VSOP
      inflammatory processes were not detectable. MRI in the presence of VSOP revealed
      inflammatory processes by the appearance of hypointense spots (hs). The
      specificity of PI to detect hs was similar to T1- and T2*-weighted images The
      calculated sensitivity was less than in corresponding T2*-weighted images.
      CONCLUSION: The diagnostic use of PI without VSOP as contrast agent to detect
      lesions is not recommended at field strength of 4.7T or lower.

PMID- 24115507
TI  - Assessment of gross motor skills and phenotype profile in children 9-11 years of
      age in survivors of acute lymphoblastic leukemia.
AB  - BACKGROUND: The purpose of this study was to evaluate the usefulness of a new
      gross motor skill test battery in acute lymphoblastic leukemia (ALL) children who
      have been off therapy for at least 1 year and to assess its discriminatory power
      (discriminant analysis) from healthy children. PROCEDURE: Twenty children (10
      males and 10 females) 9-11 years of age (median age = 10.6 years) were assessed
      by the UQAC-UQAM test battery and then compared to recent provincial norms. This
      pilot study was also an opportunity to validate this test battery as a reliable
      tool for clinical or research purposes in the area of chronic or disabling
      diseases in children. Eleven motor skill variables grouped into five factors have
      been measured (speed, agility, balance, coordination, and reaction time).
      RESULTS: Scores from 10 of the 11 motor skill tests showed significant
      differences when compared to the control group (P <= 0.05). Nearly 50% of
      patients obtained an average score below the 15th percentile. Furthermore,
      stepwise discriminant analysis allowed classifying successfully 88.4% of children
      in the correct group (ALL or Control). The normal development of GMS among
      children affected by ALL appears to have been compromised. The UQAC-UQAM test
      battery seems to be sensitive enough to quantify with precision the extent of the
      motor impairment in these children. CONCLUSION: The UQAC-UQAM test battery
      appears to be a useful tool to evaluate the extent to which ALL survivors are
      affected. Early motor intervention should be considered for those patients even
      during the treatment periods.

PMID- 24115506
TI  - Biophysical features of bacillithiol, the glutathione surrogate of Bacillus
      subtilis and other firmicutes.
AB  - Bacillithiol (BSH) is the major low-molecular-weight (LMW) thiol in many low-G+C
      Gram-positive bacteria (Firmicutes). Evidence now emerging suggests that BSH
      functions as an important LMW thiol in redox regulation and xenobiotic
      detoxification, analogous to what is already known for glutathione and mycothiol
      in other microorganisms. The biophysical properties and cellular concentrations
      of such LMW thiols are important determinants of their biochemical efficiency
      both as biochemical nucleophiles and as redox buffers. Here, BSH has been
      characterised and compared with other LMW thiols in terms of its thiol pKa ,
      redox potential and thiol-disulfide exchange reactivity. Both the thiol pKa and
      the standard thiol redox potential of BSH are shown to be significantly lower
      than those of glutathione whereas the reactivities of the two compounds in thiol
      disulfide reactions are comparable. The cellular concentration of BSH in Bacillus
      subtilis varied over different growth phases and reached up to 5 mM, which is
      significantly greater than previously observed from single measurements taken
      during mid-exponential growth. These results demonstrate that the biophysical
      characteristics of BSH are distinctively different from those of GSH and that its
      cellular concentrations can reach levels much higher than previously reported. 

PMID- 24115508
TI  - Emotion and self-cutting: narratives of service users referred to a personality
      disorder service.
AB  - Theory and existing research suggest that emotion regulation capabilities develop
      during the formative years. Emotion dysregulation is associated with
      psychological distress and may contribute towards difficulties such as
      personality disorder and self-harm. This study aimed to explore the contexts in
      which individuals' narratives of emotional experience and self-harm developed.
      Eight participants who cut themselves and were seen by a personality disorder
      service were recruited. Semi-structured interviews were carried out, and
      interview transcripts were analysed using a narrative approach. Five temporal
      themes were generated: 'Seen and not heard', 'A big release ... to get rid of all
      the pain and hurt', 'A vicious circle', 'A different world' and 'Trying to turn
      my life around'. The findings highlight how early experiences may have led
      participants to perceive emotions as unacceptable and subsequently suppress
      emotion in adulthood. Suppression of emotions appeared to be related to
      appraisals of emotions and to secondary emotional distress. Furthermore, cutting
      was linked to suppression of emotions as well as negative self-beliefs formed
      during childhood and reinforced through subsequent experiences. The study
      emphasizes the need for therapeutic approaches to focus on emotions when working
      with individuals who self-cut. Furthermore, the findings indicate the need for
      compassionate and validating health services that may help service users develop
      more optimistic future narratives.

PMID- 24115509
TI  - A systematic comparison between 1-D and 3-D hemodynamics in compliant arterial
      models.
AB  - We present a systematic comparison of computational hemodynamics in arteries
      between a one-dimensional (1-D) and a three-dimensional (3-D) formulation with
      deformable vessel walls. The simulations were performed using a series of
      idealized compliant arterial models representing the common carotid artery,
      thoracic aorta, aortic bifurcation, and full aorta from the arch to the iliac
      bifurcation. The formulations share identical inflow and outflow boundary
      conditions and have compatible material laws. We also present an iterative
      algorithm to select the parameters for the outflow boundary conditions by using
      the 1-D theory to achieve a desired systolic and diastolic pressure at a
      particular vessel. This 1-D/3-D framework can be used to efficiently determine
      material and boundary condition parameters for 3-D subject-specific arterial
      models with deformable vessel walls. Finally, we explore the impact of different
      anatomical features and hemodynamic conditions on the numerical predictions. The
      results show good agreement between the two formulations, especially during the
      diastolic phase of the cycle.

PMID- 24115510
TI  - Interpretative consequences of adopting the Global Lungs 2012 reference equations
      for spirometry for children and adolescents.
AB  - OBJECTIVE: To determine the interpretative consequences of adopting the Global
      Lungs 2012 (GLI-2012) spirometric prediction equations in a pediatric hospital
      population. MATERIAL: Spirometric records from 2,192 white boys and 1,842 white
      girls, and 412 and 334 African-American boys and girls, respectively, aged 6.0
      18.0 years, treated mainly for asthma, cystic fibrosis, cough, and dyspnoea.
      METHODS: Predicted values and lower limits of normal were calculated for FEV1,
      FVC, and FEV1/FVC, using prediction equations from GLI-2012, Hankinson, Knudson,
      Polgar, Wang, and Zapletal. Obstruction was defined as FEV1/FVC < LLN, a
      restrictive pattern as FEV1/FVC > LLN and FVC < LLN. RESULTS: There was good
      agreement for predicted values for FEV1, FVC, and FEV1/FVC from GLI-2012,
      Hankinson and Wang equations within ethnic groups. A near normal FEV1 but above
      normal FVC contributed to a low FEV1/FVC, particularly in African-Americans.
      Polgar, Knudson, and Zapletal predicteds produced disparate results. A
      restrictive pattern occurred in 2.2-11.2% of cases, with no statistical
      difference between GLI-2012 and Hankinson. CONCLUSIONS: Transition from Hankinson
      and Wang equations to GLI-2012 leads to grossly similar prevalence rates of
      abnormally low values for FEV1, FVC, and FEV1/FVC, unlike equations from Knudson,
      Polgar, and Zapletal.

PMID- 24115511
TI  - Lexical and phonological processes in dyslexic readers: evidence from a visual
      lexical decision task.
AB  - The aim of the present study was to investigate whether reading failure in the
      context of an orthography of intermediate consistency is linked to inefficient
      use of the lexical orthographic reading procedure. The performance of typically
      developing and dyslexic Portuguese-speaking children was examined in a lexical
      decision task, where the stimulus lexicality, word frequency and length were
      manipulated. Both lexicality and length effects were larger in the dyslexic group
      than in controls, although the interaction between group and frequency
      disappeared when the data were transformed to control for general performance
      factors. Children with dyslexia were influenced in lexical decision making by the
      stimulus length of words and pseudowords, whereas age-matched controls were
      influenced by the length of pseudowords only. These findings suggest that non
      impaired readers rely mainly on lexical orthographic information, but children
      with dyslexia preferentially use the phonological decoding procedure--albeit
      poorly--most likely because they struggle to process orthographic inputs as a
      whole such as controls do. Accordingly, dyslexic children showed significantly
      poorer performance than controls for all types of stimuli, including words that
      could be considered over-learned, such as high-frequency words. This suggests
      that their orthographic lexical entries are less established in the orthographic
      lexicon.

PMID- 24115512
TI  - Trace analysis of alkaline flavors in cut tobacco by heart-cutting
      multidimensional GC-GC-MS.
AB  - Tobacco is a complex chemical matrix. The analysis of trace alkaline flavors in
      tobacco is very difficult because of the limited peak capacity of monodimensional
      GC. In the present study, a home-assembled twin-oven GC-GC-MS system, with MS
      detection in both dimensions, has been applied to the analysis of 20 alkaline
      volatiles in a variety of cut-tobacco samples. By transferring nine and six heart
      cuts from the first apolar column to the second polar column in two separate
      runs, the potential mutual interference of adjacent isomeric targets and the
      complex matrix could be removed. For comparative purposes, a systematic
      comparison of both quantification and qualification results for the cut-tobacco
      sample as quality control was conducted between GC-GC-MS and GC-MS. The results
      showed that GC-GC-MS provided higher accuracy in peak assignment and
      quantification. And in GC-MS, the interferences of co-elution had caused both low
      matched similarity in peak assignment and false-negative/-positive results in
      quantification for some targets. Advantages of the developed GC-GC-MS method in
      the analysis of alkaline flavors are its high resolving power, reliability, and
      simplicity. 

PMID- 24115513
TI  - Counterintuitive anisotropy of electron transport properties in KC60(THF)5.2THF
      fulleride.

PMID- 24115514
TI  - Macrocyclic bis(phenanthroline-pyrrole): a convenient one-pot synthesis,
      structure(s), spectroscopic, and redox properties, and the binding of amine
      guests, protons, and lanthanide ions.
AB  - This paper reports a convenient, one-pot, easily scalable and readily modifiable
      synthesis of a novel large-ring bis(1,10-phenanthrolinyl-2,5-pyrrole) macrocycle,
      H2LMC, and describes its spectroscopic and electrochemical properties,
      protonation, cooperative amine binding, electrocatalysis of the oxidation of
      primary amines, photosensitization of the decomposition of dichloromethane, and
      the first lanthanide complexes of the hexaaza-dianion LMC(2-) including the novel
      dimer, [(NO3)(LMC)Eu(MU-OH)Eu(LMC )(H2 O)2].2py.

PMID- 24115515
TI  - Kinetic assembly of a thermally stable porous coordination network based on
      labile CuI units and the visualization of I2 sorption.
AB  - A net gain: A kinetically assembled, but thermally stable network is obtained
      using the labile metal species [Cu4 I4 (PPh3 )4 ]. The network uniquely adsorbs
      I2 by chemisorption through I3 (-) formation. The chemisorbed I2 readily desorbs
      above 380 K owing to the dynamic motion of the framework. A thermodynamically
      assembled network physisorbs I2 , which is an exact fit for the channel. 

PMID- 24115516
TI  - A survey of barriers to screening for oral cancer among rural Black Americans.
AB  - OBJECTIVE: Research documents a disparity between Black and White Americans in
      mortality for oral cancer that appears to result in part from behaviors such as
      lower oral cancer screening among Black Americans. We examined barriers to oral
      cancer screening among Black Americans. METHODS: We surveyed Black Americans (N =
      366) living in rural Florida to identify barriers to getting screened for oral
      cancer. RESULTS: Low knowledge/social attention, lack of resources, and
      fear/defensive avoidance predicted screening intentions, with lack of resources
      emerging as the largest barrier. Participants also reported that a recommendation
      from their provider was most likely to increase screening intentions, whereas
      encountering financial barriers was most likely to decrease screening intentions.
      CONCLUSIONS: Low knowledge/social attention, lack of resources, and
      fear/defensive avoidance emerged as independent barriers to oral cancer
      screening, with the latter two barriers accounting for the most variance in
      intentions to get screened.

PMID- 24115517
TI  - Sensitizing potential of enzymatically cross-linked peanut proteins in a mouse
      model of peanut allergy.
AB  - SCOPE: The cross-linking of proteins by enzymes to form high-molecular-weight
      protein, aggregates can be used to tailor the technological or physiological
      functionality of food products. Aggregation of dietary proteins by food
      processing may promote allergic sensitization, but the effects of enzymatic cross
      linking of dietary proteins on the allergenic potential of food are not known. In
      this study, the bioavailability and the sensitizing or tolerizing potential of
      peanut proteins (PE) cross-linked with microbial tyrosinase from Trichoderma
      reesei and mushroom tyrosinase from Agaricus bisporus, were investigated. METHODS
      AND RESULTS: The impact of cross-linking of PE on the in vitro bioavailability of
      fluorescein isothiocyanate-labeled peanut proteins was tested in a Caco-2 cell
      monolayer and by competitive ELISA. The in vivo allergenicity or capacity to
      induce oral tolerance in mice were measured by serum levels of PE-specific
      antibodies and T cell cytokine production after exposure to PE and cross-linked
      PE. CONCLUSION: Enzymatic processing of peanut proteins by the two tyrosinases
      increased the bioavailability of major peanut allergen Ara h 2, but did not
      significantly change the allergenic or tolerizing properties of peanut. Enzymatic
      treatment of peanut proteins yielded cross-linked proteins with preserved
      molecular and immunological features of peanut allergens.

PMID- 24115518
TI  - Rapid multicomponent T2 analysis of the articular cartilage of the human knee
      joint at 3.0T.
AB  - PURPOSE: To determine the feasibility of using multicomponent-driven equilibrium
      single-shot observation of T1 and T2 (mcDESPOT) for evaluating the human knee
      joint at 3.0T and to investigate depth-dependent and regional-dependent
      variations in multicomponent T2 parameters within articular cartilage. MATERIALS
      AND METHODS: mcDESPOT was performed on the knee joint of 10 asymptomatic
      volunteers at 3.0T. Single-component T2 relaxation time (T2single ),
      multicomponent T2 relaxation time for water tightly bound to proteoglycan (T2PG )
      and bulk water loosely bound to the macromolecular matrix (T2BW ), and fraction
      of water tightly bound to proteoglycan (FPG ) were measured in eight cartilage
      subsections and within the superficial and deep layers of patellar cartilage.
      Statistical analysis was used to investigate depth-dependent and regional
      dependent variations in parameters. RESULTS: There was lower (P = 0.001) T2single
      and T2PG and higher (P < 0.001) FPG in the deep than superficial layer of
      patellar cartilage. There was higher (P < 0.001) FPG on the weight-bearing
      surfaces than nonweight-bearing surfaces. There was higher (P < 0.001) T2single ,
      T2PG , and T2BW on the trochlea and posterior medial and lateral femoral condyles
      than the patella, central medial and lateral femoral condyles, and medial and
      lateral tibia plateaus. CONCLUSION: Multicomponent T2 parameters of the articular
      cartilage of the human knee joint can be measured at 3.0T using mcDESPOT and show
      depth-dependent and regional-dependent variations.

PMID- 24115520
TI  - Carbon-temperature-water change analysis for peanut production under climate
      change: a prototype for the AgMIP coordinated climate-crop modeling project
      (C3MP).
AB  - Climate change is projected to push the limits of cropping systems and has the
      potential to disrupt the agricultural sector from local to global scales. This
      article introduces the Coordinated Climate-Crop Modeling Project (C3MP), an
      initiative of the Agricultural Model Intercomparison and Improvement Project
      (AgMIP) to engage a global network of crop modelers to explore the impacts of
      climate change via an investigation of crop responses to changes in carbon
      dioxide concentration ([CO2 ]), temperature, and water. As a demonstration of the
      C3MP protocols and enabled analyses, we apply the Decision Support System for
      Agrotechnology Transfer (DSSAT) CROPGRO-Peanut crop model for Henry County,
      Alabama, to evaluate responses to the range of plausible [CO2 ], temperature
      changes, and precipitation changes projected by climate models out to the end of
      the 21st century. These sensitivity tests are used to derive crop model emulators
      that estimate changes in mean yield and the coefficient of variation for seasonal
      yields across a broad range of climate conditions, reproducing mean yields from
      sensitivity test simulations with deviations of ca. 2% for rain-fed conditions.
      We apply these statistical emulators to investigate how peanuts respond to
      projections from various global climate models, time periods, and emissions
      scenarios, finding a robust projection of modest (<10%) median yield losses in
      the middle of the 21st century accelerating to more severe (>20%) losses and
      larger uncertainty at the end of the century under the more severe representative
      concentration pathway (RCP8.5). This projection is not substantially altered by
      the selection of the AgMERRA global gridded climate dataset rather than the local
      historical observations, differences between the Third and Fifth Coupled Model
      Intercomparison Project (CMIP3 and CMIP5), or the use of the delta method of
      climate impacts analysis rather than the C3MP impacts response surface and
      emulator approach. 

PMID- 24115519
TI  - Highly functionalized terpyridines as competitive inhibitors of AKAP-PKA
      interactions.

PMID- 24115521
TI  - Diabetes mellitus in patients with thalassemia major.
AB  - BACKGROUND: Diabetes mellitus is a major endocrinopathy for patients with
      thalassemia major. Although diabetes mellitus is multifactorial, iron loading is
      its primary cause and its management poses a clinical challenge. Detecting the
      pre-diabetes stage is critical because clinical diabetes can potentially be
      reversed or prevented. PROCEDURE: Patients with thalassemia major who received
      regular blood transfusion therapy from 1994 to 2010 were evaluated for the
      incidence of diabetes mellitus and glucose dysregulation. The association between
      patients' clinical, biochemical, and image parameters was also evaluated.
      RESULTS: The patients with diabetes were significantly older, had higher ferritin
      levels, a smaller pancreas volume, and lower cardiac T2* magnetic resonance
      imaging (MRI) values than the patients without diabetes. The pancreas T2* MRI
      values were higher in the patients without diabetes, but the difference was not
      statistically significant. The liver iron concentration did not differ between
      the patients with and without diabetes. The prevalence of hepatitis C infection
      and hypogonadism was also higher in the patients with diabetes. In the patients
      without diabetes, the cardiac T2* MRI values were higher in patients with normal
      fasting glucose levels (P = 0.03), and the homeostasis model assessment of
      insulin resistance level was associated with hepatitis C infection (P = 0.024, r
      = 0.32) and hypogonadism (P = 0.034, r = 0.301). CONCLUSIONS: Fasting glucose and
      insulin levels were appropriate screening tools for evaluating glucose
      dysregulation and complemented the MRI findings. The cardiac T2* and pancreas
      volumes were significant predictors of diabetes.

PMID- 24115522
TI  - The ATP/ADP substrate specificity switch between Toxoplasma gondii NTPDase1 and
      NTPDase3 is caused by an altered mode of binding of the substrate base.
AB  - Two nucleoside triphosphate diphosphohydrolase isoforms (NTPDase1 and NTPDase3)
      are responsible for the hydrolysis of nucleotides by the intracellular protozoan
      Toxoplasma gondii. They constitute about 3 % of the total parasite protein.
      Despite sharing 97 % sequence identity they exhibit opposite ATP versus ADP
      substrate discrimination ratios. Here we show by mutagenesis that the residues
      G492/G493 in NTPDase3 and R492/E493 in NTPDase1 are predominantly responsible for
      the differences in substrate specificity. Crystal structures of NTPDase1 in
      complexation with analogues of ATP and ADP reveal that the inverted substrate
      specificity of NTPDase1 relative to NTPDase3 is achieved by switching from the
      canonical substrate binding mode to a very different alternative one. Instead of
      being stacked on top of a helix of the C-terminal domain the nucleotide base is
      positioned in the interdomain space between the side chains of R108 and R492,
      recruited from both domains. Furthermore, we show that the NTPDase1 substrate
      specificity is mainly dependent on the presence of the side chain of E493, which
      causes repositioning of the ribose component of the nucleotide. All in all,
      binding by the flexible side chains in the alternative binding mode in NTPDase1
      allows for equally good positioning of ATP and ADP with increased activity toward
      ADP relative to what is seen in the case of NTPDase3.

PMID- 24115523
TI  - Obesity and age as dominant correlates of low testosterone in men irrespective of
      diabetes status.
AB  - Although men with type 2 diabetes (T2D) frequently have lowered testosterone
      levels, it is not well established whether this is ascribable to the diabetic
      state per se, or because of other factors, such as obesity. Our objective was to
      determine the prevalence and correlates of low testosterone in middle-aged men
      with diabetes. We conducted a cross-sectional study in 240 men including 80 men
      with type 1 diabetes (T1D), 80 men with T2D and 80 men without diabetes.
      Prevalence of a total testosterone <=8 nmol/L was low, occurring in none of the
      men with T1D, 6.2% of men with T2D and 2.5% of men without diabetes. Men with T1D
      had higher testosterone levels compared with men without diabetes (p < 0.001),
      even after adjustment for body mass index (BMI) and age (p < 0.02). While men
      with T2D had lower testosterone compared with controls (p = 0.03), this was no
      longer significant when BMI and age were taken into account (p = 0.16). In the
      entire cohort, TT remained inversely associated with BMI independent of age, sex
      hormone-binding globulin and diabetic status (p = 0.01), whereas calculated free
      testosterone (cFT) was independently and inversely associated with age (p <
      0.001), but not with BMI (p = 0.47). These results suggest that marked reductions
      in circulating testosterone are uncommon in middle-aged men with diabetes.
      Increasing BMI and age are dominant drivers of lowered total and cFT,
      respectively, independent of the presence or absence of diabetes. 

PMID- 24115524
TI  - Use of a dietary exposure system for screening of insecticidal compounds for
      their toxicity to the planthopper Laodelphax striatellus.
AB  - We developed a dietary exposure assay for screening insecticidal compounds for
      their toxicity and for assessing the side effects of insecticidal proteins
      produced by genetically engineered (GE) plants on the planthopper Laodelphax
      striatellus Fallen. The fitness bioassay confirmed that the diet fulfills the
      requirements to be used in the dietary exposure system. To validate the efficacy
      of the dietary exposure system, nymphs of L. striatellus were fed diets treated
      with different concentrations of an inorganic stomach poison, potassium arsenate
      (PA), or a cysteine protease inhibitor, E-64. The results showed that with
      increasing concentrations of E-64, the larval development time was prolonged, the
      adult weight was reduced and the survival rate of L. striatellus was decreased.
      Similarly the survival rates of L. striatellus consistently decreased with
      increasing PA content in the diet. The data indicate that the dietary exposure
      assay is able to detect the effects of insecticidal compounds on L. striatellus.
      Subsequently, this assay was successfully used for assessing the potential
      toxicity of Cry2Aa. The results showed that L. striatellus larvae were not
      negatively affected when fed the artificial diet containing purified Cry2Aa at
      300 MUg/g diet. In the assay, the stability and bioactivity of crystal (Cry)
      proteins in the food sources were confirmed by enzyme-linked immunosorbent assay
      and sensitive-insect bioassays. These results show that L. striatellus is not
      sensitive to Cry2Aa. We conclude that the dietary exposure system is valid and
      useful for assessing the toxicity of insecticidal compounds produced by GE plants
      on planthoppers.

PMID- 24115525
TI  - Congenital heart defects in oculodentodigital dysplasia: Report of two cases.
AB  - Oculodentodigital dysplasia is caused by mutations in the GJA1 gene.
      Oculodentodigital dysplasia presents with a spectrum of clinical features
      including craniofacial, ocular, dental, and limb anomalies. Although recent
      findings implicate the major role of GJA1 during cardiac organogenesis,
      congenital heart defects are infrequently reported in oculodentodigital
      dysplasia. Here we report on two patients with GJA1 mutations presenting with
      cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary
      atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis.
      The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the
      fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2
      presented at 6 months with a ventricular septal defect. The child had hypoplastic
      alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de
      novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients
      underscore the importance of cardiac evaluations as part of the initial workup
      for patients with findings of oculodentodigital dysplasia. Conversely, those
      patients with type III syndactyly and congenital heart defect should be screened
      for GJA1 mutations.

PMID- 24115526
TI  - A new procedure to measure children's reading speed and accuracy in Italian.
AB  - Impaired readers in primary school should be early recognized, in order to asses
      a targeted intervention within the school and to start a teaching that respects
      the difficulties in learning to read, to write and to perform calculations.
      Screening procedures, inside the primary schools aimed at detecting children with
      difficulties in reading, are of fundamental importance for guaranteeing an early
      identification of dyslexic children and reducing both the primary negative
      effects--on learning--and the secondary negative effects--on the development of
      the personality--of this disturbance. In this study, we propose a new screening
      procedure measuring reading speed and accuracy. This procedure is very fast (it
      is exactly 1 min long), simple, cheap and can be provided by teachers without
      technical knowledge. On the contrary, most of the currently used diagnostic tests
      are about 10 min long and must be provided by experts. These two major flaws
      prevent the widespread use of these tests. On the basis of the results obtained
      in a survey on about 1500 students attending primary school in Italy, we
      investigate the relationships between variables used in the screening procedure
      and variables measuring speed and accuracy in the currently used diagnostic tests
      in Italy. Then, we analyse the validity of the screening procedure from a
      statistical point of view, and with an explorative factor analysis, we show that
      reading speed and accuracy seem to be two separate symptoms of the dyslexia
      phenomenon.

PMID- 24115527
TI  - 18F-FDG PET study reveals brain functional changes during attention in rats.
AB  - Attentional impairments are seen in many clinical syndromes, including attention
      deficit hyperactivity disorder, schizophrenia, and Alzheimer disease.
      Understanding the mechanism of attention can be helpful for the diagnosis and
      treatment of these diseases. The aim of this study was to assess brain glucose
      metabolic changes in a rat model of attention. METHODS: Small-animal PET studies
      were performed at 4 stages. Statistical parametric mapping was used for image
      analysis. RESULTS: Increased (18)F-FDG uptake was found in the lateral
      hypothalamic area and left accumbens nucleus in the learning condition. Under the
      attentive condition, increased (18)F-FDG uptake was observed in the right
      retrosplenial cortex but (18)F-FDG uptake was decreased in the right medial
      geniculate nucleus. (18)F-FDG uptake change in the right retrosplenial cortex was
      negatively correlated with correct latency of behavior performance. CONCLUSION:
      (18)F-FDG small-animal PET imaging provided novel findings on attention-related
      glucose metabolic changes, which were significantly correlated with the behavior
      performance in this rat model.

PMID- 24115528
TI  - Awake nonhuman primate brain PET imaging with minimal head restraint: evaluation
      of GABAA-benzodiazepine binding with 11C-flumazenil in awake and anesthetized
      animals.
AB  - Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational
      research approaches in humans. However, most NHP studies are conducted under
      anesthesia, which affects the interpretability of receptor binding measures. The
      aims of this study were to develop awake NHP imaging with minimal head restraint
      and to compare in vivo binding of the gamma-aminobutyric acid type A (GABAA)
      benzodiazepine radiotracer (11)C-flumazenil under anesthetized and awake
      conditions. We hypothesized that (11)C-flumazenil binding potential (BPND) would
      be higher in isoflurane-anesthetized monkeys. METHODS: The small animal PET
      scanner was fitted to a mechanical device that raised and tilted the scanner 45
      degrees  while the awake NHP was tilted back 35 degrees  in a custom chair for
      optimal brain positioning, which required acclimation of the animals to the
      chair, touch-screen tasks, intravenous catheter insertion, and tilting. For PET
      studies, the bolus-plus-constant infusion method was used for (11)C-flumazenil
      administration. Two rhesus monkeys were scanned under the awake (n = 6 scans) and
      isoflurane-anesthetized (n = 4 scans) conditions. An infrared camera was used to
      track head motion during PET scans. Under the awake condition, emission and head
      motion-tracking data were acquired for 40-75 min after injection. Anesthetized
      monkeys were scanned for 90 min. Cortisol measurements were acquired during awake
      and anesthetized scans. Equilibrium analysis was used for both the anesthetized
      (n = 4) and the awake (n = 5) datasets to compute mean BPND images in NHP
      template space, using the pons as a reference region. The percentage change per
      minute in radioactivity concentration was calculated in high- and low-binding
      regions to assess the quality of equilibrium. RESULTS: The monkeys acclimated to
      procedures in the NHP chair necessary to perform awake PET imaging. Image quality
      was comparable between awake and anesthetized conditions. The relationship
      between awake and anesthetized values was BPND (awake) = 0.94 BPND (anesthetized)
      + 0.36 (r(2) = 0.95). Cortisol levels were significantly higher under the awake
      condition (P < 0.05). CONCLUSION: We successfully performed awake NHP imaging
      with minimal head restraint. There was close agreement in (11)C-flumazenil BPND
      values between awake and anesthetized conditions.

PMID- 24115529
TI  - 123I-iodobenzamide SPECT is not an independent predictor of dopaminergic
      responsiveness in patients with suspected atypical parkinsonian syndromes.
AB  - The prediction of dopaminergic responsiveness in patients with parkinsonism is
      desirable for effective treatment strategies. We investigated whether striatal
      dopamine D2/D3 receptor (D2R) binding assessed by (123)I-iodobenzamide SPECT is
      an independent predictor of dopaminergic responsiveness in patients with
      parkinsonism. METHODS: Seventy-eight patients with clinically suspected atypical
      parkinsonian syndrome (APS) were prospectively recruited for imaging. To quantify
      striatal D2R binding, (123)I-iodobenzamide SPECT datasets were subjected to an
      observer-independent, regions-of-interest analysis. A final clinical diagnosis of
      Lewy-body disease (LBD) or APS was made after a mean follow-up of 12 mo. On the
      basis of follow-up data, dopaminergic responsiveness was classified as 0 (none),
      1 (transient), 2 (sustained mild), or 3 (sustained strong). Uni- and multivariate
      analyses of the relationship between treatment response, D2R binding, and
      confounding variables were conducted. RESULTS: Sixty patients with clinically
      verified LBD (n = 28; 22/28 with Parkinson disease) or APS (n = 32), in whom
      dopaminergic responsiveness could be assessed (n = 19/13/15/13 in categories
      0/1/2/3; 18 were excluded because of insufficient dosing), were included in the
      statistical analysis. Univariate analyses revealed that a sustained treatment
      response was significantly associated with higher D2R binding, clinical diagnosis
      of LBD, lower Hoehn and Yahr scores, and younger age. After multivariate
      correction of D2R binding for diagnosis, age, symptom duration, Hoehn and Yahr
      score, and dopaminergic pretreatment, no association was found between D2R
      binding and treatment response, either in the pooled group or in LBD or APS
      subgroups. CONCLUSION: Striatal D2R binding assessed by (123)I-iodobenzamide
      SPECT does not provide additional predictive information about treatment response
      beyond other clinical variables, most notably the clinical diagnosis.

PMID- 24115530
TI  - Three methods for 18F labeling of the HER2-binding affibody molecule Z(HER2:2891)
      including preclinical assessment.
AB  - Human epidermal growth factor receptor (HER2)-targeted Affibody molecules
      radiolabeled with (18)F allow the noninvasive assessment of HER2 status in vivo
      through PET imaging. Such agents have the potential to improve patient management
      by selecting individuals for HER2-targeted therapies and allowing therapy
      monitoring. The aim of this study was to assess different (18)F radiolabeling
      strategies of the HER2-specific Affibody molecule Z(HER2:2891), preclinically
      determine the biologic efficacy of the different radiolabel molecules, and select
      a preferred radiolabeling strategy to progress for automated manufacture.
      METHODS: Cysteine was added to the C terminus of the Affibody molecule for the
      coupling of maleimide linkers, and 3 radiolabeling strategies were assessed:
      silicon-fluoride acceptor approach ((18)F-SiFA), (18)F-AlF-NOTA, and 4-(18)F
      fluorobenzaldehyde ((18)F-FBA). The biodistributions of the radiolabeled Affibody
      molecules were then determined in naive CD-1 nude mice, and tumor targeting was
      assessed in CD-1 nude mice bearing high-HER2-expressing NCI-N87 tumors and low
      HER2-expressing A431 tumors. The (111)In-ABY-025 compound, which has demonstrable
      clinical utility, served as a reference tracer. RESULTS: The non-decay-corrected
      radiochemical yields based on starting (18)F-fluoride using the (18)F-FBA, (18)F
      SiFA, and (18)F-AlF-NOTA methods were 13% +/- 3% (n = 5), 38% +/- 2% (n = 3), and
      11% +/- 4% (n = 6), respectively. In naive mice, both the (18)F-AlF-NOTA
      Z(HER2:2891) and the (111)In-ABY-025 compounds showed a significant kidney
      retention (70.3 +/- 1.3 and 73.8 +/- 3.0 percentage injected dose [%ID],
      respectively, at 90 min after injection), which was not observed for (18)F-FBA
      Z(HER2:2891) or (18)F-SiFA-Z(HER2:2891) (4.8 +/- 0.6 and 10.1 +/- 0.7 %ID,
      respectively, at 90 min). The (18)F-SiFA-Z(HER2:2891) conjugate was compromised
      by increasing bone retention over time (5.3 +/- 1.0 %ID/g at 90 min after
      injection), indicating defluorination. All the radiolabeled Affibody molecules
      assessed showed significantly higher retention in NCI-N87 tumors than A431 tumors
      at all time points (P < 0.05), and PET/CT imaging of (18)F-FBA-Z(HER2:2891) in a
      dual NCI-N87/A431 xenograft model demonstrated high tumor-to-background contrast
      for NCI-N87 tumors. CONCLUSION: The HER2 Affibody molecule Z(HER2:2891) has been
      site-selectively radiolabeled by three (18)F conjugation methods. Preliminary
      biologic data have identified (18)F-FBA-Z(HER2:2891) (also known as GE226) as a
      favored candidate for further development and radiochemistry automation.

PMID- 24115531
TI  - Provider-caregiver-child discussions about risks associated with asthma control
      medications: content and prevalence.
AB  - OBJECTIVES: The objectives of this study were to: (1) describe the extent to
      which general pediatric providers discuss risks associated with asthma control
      medications with families, and (2) examine factors that are associated with risk
      discussions. STUDY DESIGN: This study was a cross-sectional secondary analysis of
      audio taped medical visits involving 35 pediatric providers and 248 children with
      asthma with their caregivers. Transcripts of the visits were coded for
      discussions about asthma medication risks. Generalized estimating equations were
      used to analyze the data. RESULTS: Providers discussed asthma control medication
      risks during 23% of visits. Risks were more likely to be discussed when the visit
      was longer and when the provider prescribed a new asthma control medication. When
      providers discussed asthma control medication risks, they were most likely to ask
      the family general questions and make general statements. Across all of the
      visits, caregivers asked a total of 16 questions and made a total of 20
      statements about risks associated with asthma medications; children asked a total
      of 3 questions and made two statements about risks associated with asthma control
      medications. CONCLUSION: Providers discussed risks associated with asthma control
      medications in less than one-quarter of medical visits. Providers should involve
      families in discussions about risks associated with medications during every
      visit to assess potential barriers to medication adherence.

PMID- 24115532
TI  - NHC-stabilized silagermenylidene: a heavier analogue of vinylidene.

PMID- 24115533
TI  - Influence of osteocytes in the in vitro and in vivo beta-tricalcium phosphate
      stimulated osteogenesis.
AB  - Osteocytes, known to act as the main regulators of bone homeostasis, have become
      a major focus in the field of bone research. Bioactive ceramics have been widely
      used for bone regeneration. However, there are few studies about the interaction
      of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in
      vivo osteogenesis of bioceramics are also unclear. The aim of this study was to
      investigate the role of osteocytes on the beta-tricalcium phosphate (beta-TCP)
      stimulated osteogenesis. It was found that osteocytes responded to the beta-TCP
      stimulation, leading to the release of Wnt (wingless-related MMTV integration
      site), which enhanced osteogenic differentiation of bone marrow stromal cells via
      Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an
      osteoclast inducer, was also upregulated, indicating that osteocytes would also
      participated in activation of osteoclasts, which played a major role in the
      degradation process of beta-TCP and new bone remodeling. In vivo studies further
      demonstrated that when the material was completely embedded by newly formed bone,
      the only cell contacting with the material was osteocyte. However, the material
      would eventually be degraded and replaced by the new bone, requiring the
      participation of osteoclasts and osteoblasts, which were demonstrated by using
      immunostaining in this study. As the only cell contacting with the material,
      osteocytes probably acted in a regulatory role to regulate the surrounding
      osteoclasts and osteoblasts. Osteocytes were also found to participate in the
      maturation of osteoblasts and the mineralization process of biomaterials, by
      upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These
      findings indicated that osteocytes involved in bone biomaterial-mediated
      osteogenesis and biomaterial degradation, providing valuable insights into the
      mechanism of material-stimulated osteogenesis, and a novel strategy to optimize
      the evaluating system for the biological properties of biomaterials.

PMID- 24115534
TI  - The role of Wnt/beta-catenin signaling in proliferation and regeneration of the
      developing basilar papilla and lateral line.
AB  - Canonical Wnt/beta-catenin signaling has been implicated in multiple
      developmental events including the regulation of proliferation, cell fate, and
      differentiation. In the inner ear, Wnt/beta-catenin signaling is required from
      the earliest stages of otic placode specification through the formation of the
      mature cochlea. Within the avian inner ear, the basilar papilla (BP), many Wnt
      pathway components are expressed throughout development. Here, using reporter
      constructs for Wnt/beta-catenin signaling, we show that this pathway is active
      throughout the BP (E6-E14) in both hair cells (HCs) and supporting cells. To
      characterize the role of Wnt/beta-catenin activity in developing HCs, we
      performed gain- and loss-of-function experiments in vitro and in vivo in the
      chick BP and zebrafish lateral line systems, respectively. Pharmacological
      inhibition of Wnt signaling in the BP and lateral line neuromasts during the
      periods of proliferation and HC differentiation resulted in reduced proliferation
      and decreased HC formation. Conversely, pharmacological activation of this
      pathway significantly increased the number of HCs in the lateral line and BP.
      Results demonstrated that this increase was the result of up-regulated cell
      proliferation within the Sox2-positive cells of the prosensory domains.
      Furthermore, Wnt/beta-catenin activation resulted in enhanced HC regeneration in
      the zebrafish lateral line following aminoglycoside-induced HC loss. Combined,
      our data suggest that Wnt/beta-catenin signaling specifies the number of cells
      within the prosensory domain and subsequently the number of HCs. This ability to
      induce proliferation suggests that the modulation of Wnt/beta-catenin signaling
      could play an important role in therapeutic HC regeneration.

PMID- 24115535
TI  - Multivariate optimization of surfactant-assisted directly suspended droplet
      microextraction combined with GC for the preconcentration and determination of
      tramadol in biological samples.
AB  - In this work, a novel procedure based on surfactant-assisted directly suspended
      droplet microextraction for the determination of tramadol prior to GC with flame
      ionization detection is proposed. In this technique, a free microdroplet of
      solvent is transferred to the surface of an immiscible aqueous sample containing
      Triton X-100 and tramadol while being agitated by a stirring bar placed on the
      bottom of the sample vial. After the predetermined time, the microdroplet of
      solvent is withdrawn by a syringe and analyzed. The effective parameters such as
      the type of organic solvent, extraction time, microdroplet volume, salt content
      of the donor phase, stirring speed, the source phase pH, concentration of Triton
      X-100, and extraction temperature were optimized. For this purpose, a
      multivariate strategy was applied based on an experimental design in order to
      screen and optimize the significant factors. This method requires minimal sample
      preparation, analysis time, solvent consumption, and represents significant
      advantages over customary analytical methods. The linearity ranged from 10 to
      2000 MUg/L with RSDs (n = 5) of 7.3-10. Preconcentration factors and the LODs
      were 391-466 and 2.5-6.5 MUg/L, respectively. Finally, this method was applied to
      the analysis of biological samples and satisfactory results were obtained. 

PMID- 24115537
TI  - Draft Genome Sequence of Lactobacillus plantarum Strain AY01, Isolated from the
      Raw Material of Fermented Goat Milk Cheese.
AB  - Lactobacillus plantarum is an important probiotic that is isolated mostly from
      fermented foods. Here, we report the first draft genome sequence of L. plantarum
      strain AY01, isolated from the raw material of fermented goat milk cheese. This
      bacterium, with optimum growth at 30 degrees C, has a G+C content of 43.68%. 

PMID- 24115536
TI  - Multiple reaction pathways operating in the mechanism of vinylogous Mannich-type
      reaction activated by a water molecule.
AB  - A systematic search for reaction pathways for the vinylogous Mannich-type
      reaction was performed by the artificial force induced reaction method. This
      reaction affords delta-amino-gamma-butenolide in one pot by mixing 2
      trimethylsiloxyfuran, imine, and water under solvent-free conditions.
      Surprisingly, the search identified as many as five working pathways. Among them,
      two concertedly produce anti and syn isomers of the product. Another two give an
      intermediate, which is a regioisomer of the main product. This intermediate can
      undergo a retro-Mannich reaction to give a pair of intermediates: an imine and 2
      furanol. The remaining pathway directly generates this intermediate pair. The
      imine and 2-furanol easily react with each other to afford the product. Thus, all
      of these stepwise pathways finally converge to give the main product. The rate
      determining step of all five (two concerted and three stepwise) pathways have a
      common mechanism: concerted Si-O bond formation through the nucleophilic attack
      of a water molecule on the silicon atom followed by proton transfer from the
      water molecule to the imine. Therefore, these five pathways have comparable
      barriers and compete with each other.

PMID- 24115538
TI  - Complete Genome Sequence of Pseudomonas aeruginosa Podophage MPK7, Which Requires
      Type IV Pili for Infection.
AB  - We report the complete genome sequence of Pseudomonas aeruginosa podophage MPK7.
      It displays synteny to the P. aeruginosa phages of the Phikmvlikevirus genus,
      which includes phiKMV and LKA1. MPK7 requires type IV pili (TFP) for infection,
      suggesting the role of functional TFP as the receptor for this phage genus. 

PMID- 24115539
TI  - Draft Genome Sequence of Xylella fastidiosa subsp. multiplex Strain Griffin-1
      from Quercus rubra in Georgia.
AB  - The draft genome sequence of Xylella fastidiosa subsp. multiplex strain Griffin
      1, isolated from a red oak tree (Quercus rubra) in Georgia, is reported here. The
      bacterium has a genome size of 2,387,314 bp, with a G+C content of 51.7%. The
      Griffin-1 strain genome contains 2,903 predicted open reading frames and 50 RNA
      genes. 

PMID- 24115540
TI  - Draft Genome Sequences of Strains of Pasteurella multocida Isolated from the
      United Kingdom and the United States.
AB  - Pasteurella multocida is a major pathogen of farm animals and has worldwide
      distribution. Here we report the draft genome sequences of four strains that were
      isolated from animals in the United Kingdom and the United States and represent
      pathogenic and commensal presentation of the bacterium. 

PMID- 24115541
TI  - Draft Genome Sequence of Brucella melitensis Strain ADMAS-G1, Isolated from
      Placental Fluids of an Aborted Goat.
AB  - Here, we report the draft genome sequence and annotation of the Brucella
      melitensis strain designated ADMAS-G1, isolated from placental fluids of an
      aborted goat. The length of the genome is 3,284,982 bp, with a 57.3% GC content.
      A total of 3,325 protein-coding genes and 63 RNA genes were predicted. 

PMID- 24115542
TI  - Draft Genome Sequence of Gallibacterium anatis bv. haemolytica 12656-12 Liver, an
      Isolate Obtained from the Liver of a Septicemic Chicken.
AB  - We report the draft genome sequence of Gallibacterium anatis bv. haemolytica
      strain 12656-12 Liver. This strain was isolated from the liver of a septicemic
      layer chicken in Denmark in 1981. The strain has been used extensively for
      experimental purposes. 

PMID- 24115543
TI  - Complete genome sequence of a nephropathogenic infectious bronchitis virus strain
      isolated in china.
AB  - Infectious bronchitis virus (IBV) causes tremendous economic losses to the
      poultry industry. Here, we report the complete genome analysis results for a new
      natural recombination nephropathogenic IBV strain named SAIBK, which was isolated
      in the Sichuan province of China in 2005. 

PMID- 24115544
TI  - Draft Genome Sequence of Bacillus sp. Strain SB47, an Obligate Extreme Halophile
      Isolated from a Salt Pan of the Little Rann of Kutch, India.
AB  - Here, we report the 4.46-Mbp draft genome sequence of Bacillus sp. strain SB47,
      an extreme halophile isolated from a salt pan of the Little Rann of Kutch, India.
      Exploring the genome of this organism will facilitate the understanding and
      isolation of the gene(s) involved in its extreme osmotolerance. 

PMID- 24115545
TI  - Draft Genome Sequence of Bacillus thuringiensis var. thuringiensis Strain T01
      328, a Brazilian Isolate That Produces a Soluble Pesticide Protein, Cry1Ia.
AB  - Bacillus thuringiensis var. thuringiensis strain T01-328, isolated from Cubatao
      county (Sao Paulo State, Brazil), produces a soluble pesticide protein, Cry1Ia,
      during vegetative growth. Here, we report the 7.089-Mbp draft genome sequence,
      composed of a 5.5-Mb chromosome and 14 plasmids, which is the largest B.
      thuringiensis genome sequenced to date. 

PMID- 24115546
TI  - Genome Sequence of Halomonas sp. Strain A3H3, Isolated from Arsenic-Rich Marine
      Sediments.
AB  - We report the genome sequence of Halomonas sp. strain A3H3, a bacterium with a
      high tolerance to arsenite, isolated from multicontaminated sediments of the
      l'Estaque harbor in Marseille, France. The genome is composed of a 5,489,893-bp
      chromosome and a 157,085-bp plasmid. 

PMID- 24115547
TI  - Genome Sequence of Human Herpesvirus 7 Strain UCL-1.
AB  - The sequence of human herpesvirus 7 (HHV-7) strain UCL-1 was determined using
      target enrichment and next-generation sequencing methods. We have identified 86
      putative open reading frames (ORFs), and comparative sequence analyses
      demonstrate that this strain is closely related to the previously sequenced HHV-7
      strains RK and JI. 

PMID- 24115548
TI  - Draft Genome Sequence of a Meningitic Isolate of Cronobacter sakazakii Clonal
      Complex 4, Strain 8399.
AB  - The Cronobacter sakazakii clonal lineage defined as clonal complex 4 (CC4),
      composed of nine sequence types, is associated with severe cases of neonatal
      meningitis. To date, only closely related C. sakazakii sequence type 4 (ST4)
      strains have been sequenced. C. sakazakii strain 8399, isolated from a case of
      neonatal meningitis, was sequenced as the first non-ST4 C. sakazakii strain. 

PMID- 24115549
TI  - Draft Genome Sequence of a Stable Mucoid Strain of Pseudomonas aeruginosa PAO581
      with a mucA25 Mutation.
AB  - A mutation in the mucA gene, which encodes a negative regulator of alginate
      production in Pseudomonas aeruginosa, is the main mechanism underlying the
      conversion to mucoidy in clinical isolates from patients with cystic fibrosis
      (CF). Here, we announce the draft genome sequence of the stable alginate
      overproducing mucoid strain P. aeruginosa PAO581 with a mucA25 mutation, a
      derivative from the nonmucoid strains P. aeruginosa PAO381 and PAO1. 

PMID- 24115550
TI  - Draft Genome Sequence of Bacillus sp. Strain NSP9.1, a Moderately Halophilic
      Bacterium Isolated from the Salt Marsh of the Great Rann of Kutch, India.
AB  - We report the 4.52-Mbp draft genome sequence of Bacillus sp. strain NSP9.1, a
      moderately halophilic bacterium isolated from the salt marsh of the Great Rann of
      Kutch, India. Analysis of the genome of this organism will lead to a better
      understanding of the genes and metabolic pathways involved in imparting
      osmotolerance. 

PMID- 24115551
TI  - Identification of a Genotype IX Newcastle Disease Virus in a Guangxi White Duck.
AB  - We report the complete genomic sequence of a novel Newcastle disease virus (NDV)
      strain, duck/China/Guangxi19/2011, isolated from a white duck in Guangxi
      Province, southern China. Phylogenetic analysis based on a fusion gene comparison
      with different NDV strains revealed that duck/China/Guangxi19/2011 is
      phylogenetically close to genotype IX NDV, and the deduced amino acid sequence of
      the fusion protein cleavage site was 112R-R-Q-R-R-F117. The whole nucleotide
      sequence had the highest homology (99.7%) to the sequence of strain F48E8
      (GenBank accession number FJ436302). This study will help us understand the
      epidemiology and molecular characteristics of genotype IX Newcastle disease virus
      in ducks. 

PMID- 24115552
TI  - Draft Genome Sequence of a Mucoid Isolate of Pseudomonas aeruginosa Strain C7447m
      from a Patient with Cystic Fibrosis.
AB  - Alginate overproduction by Pseudomonas aeruginosa, or mucoidy, plays an important
      role in the pathogenesis of chronic lung infections in cystic fibrosis (CF)
      patients. Here we report the draft genome sequence of a clinical isolate of
      mucoid P. aeruginosa strain C7447m from a CF patient with chronic lung infection.

PMID- 24115553
TI  - DNA as a molecular local thermal probe for the analysis of magnetic hyperthermia.
AB  - Too hot to handle: The surroundings of magnetic nanoparticles can be heated by
      applying a magnetic field. Polymer-coated magnetic nanoparticles were
      functionalized with single-stranded DNA molecules and further hybridized with DNA
      modified with different fluorophores. By correlating the denaturation profiles of
      the DNA with the local temperature, temperature gradients for the vicinity of the
      excited nanoparticles were determined. 

PMID- 24115555
TI  - In situ electron microscopy four-point electromechanical characterization of
      freestanding metallic and semiconducting nanowires.
AB  - Electromechanical coupling is a topic of current interest in nanostructures, such
      as metallic and semiconducting nanowires, for a variety of electronic and energy
      applications. As a result, the determination of structure-property relations that
      dictate the electromechanical coupling requires the development of experimental
      tools to perform accurate metrology. Here, a novel micro-electro-mechanical
      system (MEMS) that allows integrated four-point, uniaxial, electromechanical
      measurements of freestanding nanostructures in-situ electron microscopy, is
      reported. Coupled mechanical and electrical measurements are carried out for
      penta-twinned silver nanowires, their resistance is identified as a function of
      strain, and it is shown that resistance variations are the result of nanowire
      dimensional changes. Furthermore, in situ SEM piezoresistive measurements on n
      type, [111]-oriented silicon nanowires up to unprecedented levels of ~7% strain
      are demonstrated. The piezoresistance coefficients are found to be similar to
      bulk values. For both metallic and semiconducting nanowires, variations of the
      contact resistance as strain is applied are observed. These variations must be
      considered in the interpretation of future two-point electromechanical
      measurements. 

PMID- 24115554
TI  - MRI of the hip at 7T: feasibility of bone microarchitecture, high-resolution
      cartilage, and clinical imaging.
AB  - PURPOSE: To demonstrate the feasibility of performing bone microarchitecture,
      high-resolution cartilage, and clinical imaging of the hip at 7T. MATERIALS AND
      METHODS: This study had Institutional Review Board approval. Using an 8-channel
      coil constructed in-house, we imaged the hips of 15 subjects on a 7T magnetic
      resonance imaging (MRI) scanner. We applied: 1) a T1-weighted 3D fast low angle
      shot (3D FLASH) sequence (0.23 * 0.23 * 1-1.5 mm(3) ) for bone microarchitecture
      imaging; 2) T1-weighted 3D FLASH (water excitation) and volumetric interpolated
      breath-hold examination (VIBE) sequences (0.23 * 0.23 * 1.5 mm(3) ) with
      saturation or inversion recovery-based fat suppression for cartilage imaging; 3)
      2D intermediate-weighted fast spin-echo (FSE) sequences without and with fat
      saturation (0.27 * 0.27 * 2 mm) for clinical imaging. RESULTS: Bone
      microarchitecture images allowed visualization of individual trabeculae within
      the proximal femur. Cartilage was well visualized and fat was well suppressed on
      FLASH and VIBE sequences. FSE sequences allowed visualization of cartilage, the
      labrum (including cartilage and labral pathology), joint capsule, and tendons.
      CONCLUSION: This is the first study to demonstrate the feasibility of performing
      a clinically comprehensive hip MRI protocol at 7T, including high-resolution
      imaging of bone microarchitecture and cartilage, as well as clinical imaging.

PMID- 24115556
TI  - A fluorogenic probe for gamma-glutamyl cyclotransferase: application of an enzyme
      triggered O-to-N acyl migration-type reaction.
AB  - Light it up: human chromosome 7 ORF 24, a tumor-related protein, has been
      identified as a gamma-glutamyl cyclotransferase (GGCT) in the glutathione
      homeostasis cycle. The singular substrate preference of the enzyme has hampered
      chemical probe development, and no fluorogenic probe has been reported. Here we
      report the first fluorogenic dipeptide probe, LISA-4, which should contribute
      toward further understanding of GGCT.

PMID- 24115557
TI  - Light-activated electroactive molecule-based memory microcells confined on a
      silicon surface.

PMID- 24115558
TI  - Severe growth retardation, delayed bone age, and facial dysmorphism in two
      patients with microduplications in 2p16 -> p22.
AB  - Interstitial duplications of the short arm of chromosome 2 have been rarely
      described. Here, we report on two unrelated patients with overlapping chromosome
      2p16 -> p22 de novo microduplications found by SNP-array analysis. The affected
      individuals were an 8-year-3-month-old boy with a direct duplication of
      approximately 14.6 Mb harboring 63 genes, and a 12-year-old girl with a direct
      duplication of around 9.6 Mb harboring 48 genes. Both patients have severe growth
      retardation, delayed bone age, prominent veins on trunk and extremities, total
      IGF1 level in the low range, mild developmental delay, and facial dysmorphism
      such as relative macrocephaly, a broad and prominent forehead, and a large
      anterior fontanelle. Comparison with patients previously reported in the
      literature and in the DECIPHER 5.1 and ECARUCA databases indicates a common
      region of interest of around 1.9 Mb responsible for most of the features. Two
      candidate genes (EPAS and RHOQ), may be particularly relevant for the marked
      growth retardation and developmental delay.

PMID- 24115559
TI  - Congenital thrombotic thrombocytopenic purpura with novel mutations in three
      unrelated Turkish children.
AB  - Congenital thrombotic thrombocytopenic purpura (TTP) is an inherited disease
      caused by mutations in the ADAMTS 13 gene and has been reported to have diverse
      ages of presentation, ranging from the newborn period to adulthood. Herein, we
      present three cases of congenital TTP who were symptomatic during childhood
      (neonatal period, 7 and 10 years) and were each initially given different
      diagnoses. Congenital TTP was later diagnosed by molecular analysis and
      responsiveness to fresh frozen plasma. Three novel mutations in a homozygous
      state were identified in these patients: c.1308G>C, c.428T>C (p.Ile143Thr) and
      c.1709A>G (p.Tyr570Cys).

PMID- 24115560
TI  - Clinical analysis of the characterization of magnetic resonance imaging in 102
      cases of refractory haematospermia.
AB  - To analyze the pathogenesis of persistent and refractory haematospermia and to
      evaluate the aetiological diagnostic value of magnetic resonance imaging (MRI)
      for this type of haematospermia. Clinical data from 102 patients with persistent
      and refractory haematospermia was retrospectively analysed. Data collected
      included history, symptoms, as well as ultrasound and MRI of the morphological
      features of the bilateral seminal vesicles (SV) and ejaculatory duct (ED) areas.
      Criteria for inclusion were haematospermia symptoms that occurred more than six
      times, that lasted more than 6 months, and that did not improve after >1 month of
      conservative treatment. Patients underwent seminal vesiculoscopy with a post
      surgery follow-up of 3-48 months [average (18.1 +/- 10.3) months]. Of the 102
      patients that underwent MRI examination, data from 88 patients (86.3%) showed
      typical and characteristic changes in the ED area, including the signal intensity
      changes in 60 (58.8%), SV volume changes in 32(31.4%), the formation of cysts
      such as prostatic utricular cysts in 27 (26.5%), Mullerian cysts in 4 (3.9%), ED
      cysts in 5 (4.9%) and a SV cyst in 1(1.0%). The MRI findings were confirmed by
      seminal vesiculoscopy and all patients received appropriate treatment. In 14
      patients (13.7%), no obvious abnormal changes were observed with MRIs, however,
      these patients were diagnosed and successfully managed using seminal
      vesiculoscopy. Some degrees of ED obstruction was usually found during surgery.
      The symptoms of haematospermia disappeared 1-2 months after surgery in all
      patients. Two patients had a recurrence of haematospermia, underwent the same
      treatment, and recovered during the follow-up period. The aetiology of the most
      cases of the refractory haematospermia can be distinguished using the three
      dimensional MRI. Typical abnormalities observed on MR images are signal
      intensity, SV volume changes and cyst formation. MRI has significant etiological
      diagnostic value and provides reliable information for the subsequent treatment
      of patients with persistent and refractory haematospermia. 

PMID- 24115562
TI  - Selective methylation of amines with carbon dioxide and H2.

PMID- 24115561
TI  - Extended-release opioids in the management of cancer pain: a systematic review of
      efficacy and safety.
AB  - Despite the increased availability of strong analgesics and evidence-based
      recommendations for pain management, under-treatment of cancer-related pain is
      still common. Extended-release (ER) opioids, in contrast to immediate-release
      opioids, provide prolonged analgesia. In this review, we aimed to compare the
      efficacy and safety of ER opioid analgesics in managing moderate-to-severe pain
      in patients with cancer. We identified randomized controlled trials (RCTs) and
      controlled observational studies that compared ER opioids in cancer pain by
      searching several databases, including MEDLINE, EMBASE and the Cochrane Library.
      Two independent reviewers screened and evaluated retrieved records to select
      relevant studies. We dually assessed the risk of bias for included studies and
      evaluated the overall strength of evidence for six critical outcomes using
      Grading of Recommendations Assessment, Development and Evaluation level of
      evidence. A total of three double-blind RCTs (comparative efficacy and adverse
      events), two non-blinded RCTs and four observational studies (comparative adverse
      events) were included in this review. All randomized trials and one observational
      study were of high risk of bias, and three observational studies of unclear risk
      of bias. The level of evidence for the selected efficacy and safety outcomes was
      low and very low. We synthesized the findings qualitatively because of the
      paucity of relevant studies as well as variable study design and quality. This
      systematic review indicates no substantial differences in efficacy and frequent
      adverse events among ER opioids for cancer pain. The body of evidence, however,
      is limited to few comparisons and fraught with methodological shortcomings. 

PMID- 24115563
TI  - A new class of bioactive glasses: calcium-magnesium sulfophosphates.
AB  - Low-melting ionic sulfophosphate glasses from the system P2O5-SO4-MO-Na2O (M =
      Zn(2+), Ca(2+) or Mg(2+)) have been previously shown by us to allow tuneable
      aqueous dissolution and also enable processing temperatures well below 400
      degrees C. Sulfate ions are extremely safe for use in the body as decades of use
      of calcium sulfate bone grafts testifies and there is no known limit on their
      adult oral toxicity. This glass system therefore offers great potential for use
      as biomaterials, especially in organic-inorganic hybrid systems such as glass
      polymer composites for tissue engineering or drug encapsulation and delivery
      applications. A compositional region was identified where stable sulfophosphates
      of the type P2O5-SO4-(Ca, Mg, Zn)O-Na2O can be fabricated. For these glasses, the
      viscosity-temperature-dependence, glass transformation temperatures (Tg ) and the
      onset of crystallization were evaluated as the primary processing parameters. As
      a first step in exploring their potential as a biomaterial, in this study we
      examine the bioactivity of several compositions of these glasses using
      fibroblast, monocyte, and osteoclast cell culture models to determine cellular
      responses in terms of attachment, proliferation, differentiation, and toxicity.

PMID- 24115564
TI  - Investigation of vinegar production using a novel shaken repeated batch culture
      system.
AB  - Nowadays, bioprocesses are developed or optimized on small scale. Also, vinegar
      industry is motivated to reinvestigate the established repeated batch
      fermentation process. As yet, there is no small-scale culture system for
      optimizing fermentation conditions for repeated batch bioprocesses. Thus, the aim
      of this study is to propose a new shaken culture system for parallel repeated
      batch vinegar fermentation. A new operation mode - the flushing repeated batch -
      was developed. Parallel repeated batch vinegar production could be established in
      shaken overflow vessels in a completely automated operation with only one pump
      per vessel. This flushing repeated batch was first theoretically investigated and
      then empirically tested. The ethanol concentration was online monitored during
      repeated batch fermentation by semiconductor gas sensors. It was shown that the
      switch from one ethanol substrate quality to different ethanol substrate
      qualities resulted in prolonged lag phases and durations of the first batches. In
      the subsequent batches the length of the fermentations decreased considerably.
      This decrease in the respective lag phases indicates an adaptation of the acetic
      acid bacteria mixed culture to the specific ethanol substrate quality.
      Consequently, flushing repeated batch fermentations on small scale are valuable
      for screening fermentation conditions and, thereby, improving industrial-scale
      bioprocesses such as vinegar production in terms of process robustness,
      stability, and productivity.

PMID- 24115565
TI  - Optimizing rice yields while minimizing yield-scaled global warming potential.
AB  - To meet growing global food demand with limited land and reduced environmental
      impact, agricultural greenhouse gas (GHG) emissions are increasingly evaluated
      with respect to crop productivity, i.e., on a yield-scaled as opposed to area
      basis. Here, we compiled available field data on CH4 and N2 O emissions from rice
      production systems to test the hypothesis that in response to fertilizer nitrogen
      (N) addition, yield-scaled global warming potential (GWP) will be minimized at N
      rates that maximize yields. Within each study, yield N surplus was calculated to
      estimate deficit or excess N application rates with respect to the optimal N rate
      (defined as the N rate at which maximum yield was achieved). Relationships
      between yield N surplus and GHG emissions were assessed using linear and
      nonlinear mixed-effects models. Results indicate that yields increased in
      response to increasing N surplus when moving from deficit to optimal N rates. At
      N rates contributing to a yield N surplus, N2 O and yield-scaled N2 O emissions
      increased exponentially. In contrast, CH4 emissions were not impacted by N
      inputs. Accordingly, yield-scaled CH4 emissions decreased with N addition.
      Overall, yield-scaled GWP was minimized at optimal N rates, decreasing by 21%
      compared to treatments without N addition. These results are unique compared to
      aerobic cropping systems in which N2 O emissions are the primary contributor to
      GWP, meaning yield-scaled GWP may not necessarily decrease for aerobic crops when
      yields are optimized by N fertilizer addition. Balancing gains in agricultural
      productivity with climate change concerns, this work supports the concept that
      high rice yields can be achieved with minimal yield-scaled GWP through optimal N
      application rates. Moreover, additional improvements in N use efficiency may
      further reduce yield-scaled GWP, thereby strengthening the economic and
      environmental sustainability of rice systems. 

PMID- 24115566
TI  - Integration of anterior neural plate patterning and morphogenesis by the Wnt
      signaling pathway.
AB  - Wnts are essential for a multitude of processes during embryonic development and
      adult homeostasis. The molecular structure of the Wnt pathway is extremely
      complex, and it keeps growing as new molecular components and novel interactions
      are uncovered. Recent studies have advanced our understanding on how the diverse
      molecular outcomes of the Wnt pathway are integrated during organ development, an
      integration that is also essential, although mechanistically poorly understood,
      during the formation of the anterior part of the nervous system, the forebrain.
      In this article, the author has summarized these findings and discussed their
      implications for forebrain development. A special emphasis has been put forth on
      studies performed in the zebrafish as this model system has been instrumental for
      our current understanding of forebrain patterning.

PMID- 24115567
TI  - Simultaneous determination of four aflatoxins and ochratoxin A in ginger and
      related products by HPLC with fluorescence detection after immunoaffinity column
      clean-up and postcolumn photochemical derivatization.
AB  - Ginger, a widely used spice and traditional Chinese medicine, is prone to be
      contaminated by mycotoxins. A simple, sensitive, and reproducible method based on
      immunoaffinity column clean-up coupled with HPLC and on-line postcolumn
      photochemical derivatization with fluorescence detection was developed for the
      simultaneous determination of aflatoxins (AFs) B1 , B2 , G1 , G2 , and ochratoxin
      A (OTA) in 25 batches of gingers and related products marketed in China for the
      first time. The samples were first extracted by ultrasonication with
      methanol/water (80:20, v/v) and then cleaned up with immunoaffinity columns for
      analysis. Under the optimized conditions, the LODs and LOQs for the five
      mycotoxins were 0.03-0.3 and 0.1-0.9 MUg/kg, respectively. The average recoveries
      ranged from 81.3-100.8% for AFs and from 88.6-99.5% for OTA at three spiking
      levels. Good linearity was observed for the analytes with correlation
      coefficients all >0.9995. All moldy gingers were contaminated with at least one
      kind of the five investigated mycotoxins, while none of them were found in normal
      gingers. Ginger powder samples were contaminated slightly with the contamination
      levels below the LOQs, while ginger tea bags were mainly contaminated by OTA at
      1.05-1.19 MUg/kg and ginger black tea bags were mainly contaminated by AFs at
      3.37-5.76 MUg/kg. All the contamination levels were below the legally allowable
      limits. 

PMID- 24115568
TI  - Chitosan-capped mesoporous silica nanoparticles as pH-responsive nanocarriers for
      controlled drug release.
AB  - Herein, we present a straightforward synthesis of pH-responsive chitosan-capped
      mesoporous silica nanoparticles (MSNs). These MCM-41-type MSNs could be used as
      nanocapsules to accommodate guest molecules. Subsequently, (3
      glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs,
      which served as a bridge to link between MSNs and chitosan, which is ubiquitous
      in nature and commercially available. Owing to the pH-responsive and
      biocompatible features of chitosan, the loading and release of an anti-cancer
      drug, doxorubicin hydrochloride, were carried out in vitro, in which the
      composite chitosan-capped MSNs (CS-MSNs) showed excellent environmental response.
      As the pH value of the media decreased, the degree of drug release
      correspondingly increased. Moreover, thanks to the perfect biocompatibility of
      chitosan, the CS-MSNs exhibited lower cytotoxicity than that of the naked MSNs in
      an MTT assay. In addition, the in vitro kill potency against MCF-7 breast-cancer
      cells was enhanced over time, as well as with increasing concentration of the
      drug-loaded CS-MSNs. These results indicate that CS-MSNs are promising candidates
      for pH-responsive drug delivery in cancer therapy.

PMID- 24115569
TI  - Should physical activity recommendation depend on state of low back pain?
AB  - BACKGROUND: Leisure time physical activity is recommended for preventing long
      term sickness absence (LTSA). Although low back pain (LBP) is a risk factor for
      sickness absence and physical activity is recommended for people with LBP, it is
      unknown if leisure time physical activity prevents LTSA among persons with
      different levels of LBP. METHODS: Prospective cohort study among 8655 Danish
      female healthcare workers responding to a questionnaire in 2004-2005 on leisure
      time physical activity and LBP, and subsequently followed for 1 year on periods
      with LTSA ~2 consecutive weeks or more of sickness absence in a national register
      of social transfer payments (DREAM). Multi-adjusted Cox regression analysis was
      used to model risk estimates for LTSA associated with low, moderate, high and
      very high leisure time physical activity at baseline among healthcare workers
      with no LBP (0 days past 12 months, n = 2761), non-chronic LBP (1-30 days the
      past 12 months, n = 3942) and persistent LBP (>30 days the past 12 months, n =
      1952). RESULTS: A strongly reduced risk for LTSA from high leisure time physical
      activity was found among healthcare workers with no LBP [hazard ratio (HR): 95%
      confidence interval (CI) 0.47:0.23-0.97 for low vs. very high activity] and non
      chronic LBP (HR: 95%CI 0.43:0.23-0.84 of low vs. very high activity), but not
      among healthcare workers with persistent LBP (HR: 95%CI 1.15:0.55-2.44 of low vs.
      very high activity). CONCLUSIONS: Leisure time physical activity is a strong
      predictive factor on LTSA among female healthcare workers with no and non-chronic
      LBP, but not among those with more persistent LBP.

PMID- 24115570
TI  - Rubinstein-Taybi syndrome predisposing to non-WNT, non-SHH, group 3
      medulloblastoma.
AB  - Medulloblastomas (MB) are classified in four subgroups: the well defined WNT and
      Sonic Hedgehog (SHH) subgroups, and the less defined groups 3 and 4. They
      occasionally occur in the context of a cancer predisposition syndrome. While
      germline APC mutations predispose to WNT MB, germline mutations in SUFU, PTCH1,
      and TP53 predispose to SHH tumors. We report on a child with a Rubinstein-Taybi
      syndrome (RTS) due to a germline deletion in CREBBP, who developed a MB.
      Biological profilings demonstrate that this tumor belongs to the group 3. RTS may
      therefore be the first predisposition syndrome identified for non-WNT/non-SHH MB.

PMID- 24115571
TI  - Quantitative MRI of articular cartilage and its clinical applications.
AB  - Cartilage is one of the most essential tissues for healthy joint function and is
      compromised in degenerative and traumatic joint diseases. There have been
      tremendous advances during the past decade using quantitative MRI techniques as a
      noninvasive tool for evaluating cartilage, with a focus on assessing cartilage
      degeneration during osteoarthritis (OA). In this review, after a brief overview
      of cartilage composition and degeneration, we discuss techniques that grade and
      quantify morphologic changes as well as the techniques that quantify changes in
      the extracellular matrix. The basic principles, in vivo applications, advantages,
      and challenges for each technique are discussed. Recent studies using the OA
      Initiative (OAI) data are also summarized. Quantitative MRI provides noninvasive
      measures of cartilage degeneration at the earliest stages of joint degeneration,
      which is essential for efforts toward prevention and early intervention in OA.

PMID- 24115573
TI  - Human papillomavirus-related head and neck squamous cell carcinoma.

PMID- 24115572
TI  - Inhibition of p38 MAPK sensitizes tumour cells to cisplatin-induced apoptosis
      mediated by reactive oxygen species and JNK.
AB  - The p38 MAPK pathway is an important regulator of many cellular responses. It is
      well established that p38 MAPK signalling negatively regulates epithelial cell
      transformation, but enhanced p38 MAPK activity has been also correlated with bad
      clinical prognosis in some tumour types. Here, we provide genetic and
      pharmacological evidence showing that p38 MAPK inhibition cooperates with the
      chemotherapeutic agent cisplatin to kill tumour cells. We show that p38 MAPK
      inhibition results in ROS upregulation, which in turn activates the JNK pathway
      via inactivation of phosphatases, sensitizing human tumour cells to cisplatin
      induced apoptosis. Using a mouse model for breast cancer, we confirm that
      inhibition of p38 MAPK cooperates with cisplatin treatment to reduce tumour size
      and malignancy in vivo. Taken together, our results illustrate a new function of
      p38 MAPK that helps tumour cells to survive chemotherapeutic drug treatments, and
      reveal that the combination of p38 MAPK inhibitors with cisplatin can be
      potentially exploited for cancer therapy.

PMID- 24115574
TI  - Specific sperm defects are differentially correlated with DNA fragmentation in
      both normozoospermic and teratozoospermic subjects.
AB  - A positive effect of selecting spermatozoa under high magnification during
      intracytoplasmic sperm injection (ICSI) has been described, but a clear
      explanation has not been given yet. Previous works have shown that high
      magnification selected spermatozoa have significantly better chromatin status
      than unselected cells; on the other hand, it has been reported that spermatozoa
      with no morphological defects can also be negatively associated with embryo
      quality and pregnancy outcome attributable to DNA fragmentation. The aim of this
      study was to investigate whether sperm morphology is correlated with DNA
      fragmentation, both in normozoospermic and teratozoospermic patients. A
      prospective cohort study involving 32 subjects was recruited over a 3-month
      period. Spermatozoa were fixed on a slide for TUNEL assay and evaluated using an
      epifluorescent light microscope equipped with a video monitor. Single TUNEL
      positive or -negative cells were evaluated for morphology at *4400 magnification.
      Each spermatozoon was then classified according to morphological normalcy or
      specific defects. The median percentage of typical forms was 11 and 0%, in the
      normozoospermic and teratozoospermic groups respectively (p = 0.001). In
      normozoospermic samples, the percentage of TUNEL-positive morphologically normal
      spermatozoa was 4%. By comparison, spermatozoa showing a vacuolated head or a
      small non-oval head had a significantly higher incidence of DNA fragmentation in
      both groups (12 and 13%, 19 and 13% respectively; p < 0.05). In contrast,
      spermatozoa showing a pyriform head had a DNA fragmentation rate similar to
      typical forms (3 and 5%, in normozoospermic and teratozoospermic respectively).
      This study shows that specific defects evaluated in fixed spermatozoa under high
      power magnification are more likely to be associated with DNA fragmentation. High
      magnification evaluation of spermatozoa can therefore reduce the probability of
      selecting cells carrying fragmented DNA during ICSI. 

PMID- 24115575
TI  - Cobalt(II)-catalyzed asymmetric olefin cyclopropanation with alpha
      ketodiazoacetates.

PMID- 24115576
TI  - High-resolution analysis of copy number variants in adults with simple-to
      moderate congenital heart disease.
AB  - As patients with congenital heart disease (CHD) increasingly survive to
      childbearing age, it becomes important to understand the genetic origins of CHD.
      In children, CHD is frequently caused by chromosomal imbalances. We searched for
      submicroscopic imbalances in adults with CHD focusing on simple-to-moderate
      phenotypes, without associated dysmorphic features, a group not previously
      examined. A total of 100 Han Chinese adults with a diverse range of isolated CHD
      and 65 ethnically matched controls were screened using whole-genome array
      comparative genomic hybridization. Forty-five large (>100 kb) rare copy number
      variants (CNVs) were identified in 36/100 patients. These variants were not
      listed in the Database of Genomic Variants nor found in controls. In three of
      these genomic imbalances (22q11.2, 18q23, 3q21.3), genes that play an important
      role in cardiac development were implicated, including CRKL, NFATC1, PLXNA1, the
      latter has not been associated with human CHD before. This study detected a 0.7
      Mb 22q11.2 deletion, which marginally overlapped the common 3 Mb 22q11.2
      deletion, in one patient with a perimembranous ventricular septal defect without
      any extracardiac manifestation. Furthermore, we detected a novel inherited
      aberration dup (16q23.1). Although a causal relationship with CHD remains to be
      established, this CNVs profile provides a spectrum of genomic imbalances in this
      condition, and improves the CNV-phenotype correlations.

PMID- 24115577
TI  - Towards the rational design of efficient organic structure-directing agents for
      zeolite synthesis.
AB  - Zeolites are crystalline microporous materials with application in diverse
      fields, especially in catalysis. The ability to prepare zeolites with targeted
      physicochemical properties for a specific catalytic application is a matter of
      great interest, because it allows the efficiency of the entire chemical process
      to be increased (higher product yields, lower undesired by-products, less energy
      consumption, and cost savings, etc). Nevertheless, directing the zeolite
      crystallization towards the material with the desired framework topology, crystal
      size, or chemical composition is not an easy task, since several variables
      influence the nucleation and crystallization processes. The combination of
      accumulated knowledge, rationalization, and innovation has allowed the synthesis
      of unique zeolitic structures in the last few years. This is especially true in
      terms of the design of organic and inorganic structure-directing agents (SDAs).
      In this Minireview we will present the rationale we have followed in our studies
      to synthesize new zeolite structures, while putting this in perspective with the
      advances made by other researchers of the zeolite community. 

PMID- 24115578
TI  - Acquisition of thermotolerant yeast Saccharomyces cerevisiae by breeding via
      stepwise adaptation.
AB  - A thermotolerant Saccharomyces cerevisiae yeast strain, YK60-1, was bred from a
      parental strain, MT8-1, via stepwise adaptation. YK60-1 grew at 40 degrees C, a
      temperature at which MT8-1 could not grow at all. YK60-1 exhibited faster growth
      than MT8-1 at 30 degrees C. To investigate the mechanisms how MT8-1 acquired
      thermotolerance, DNA microarray analysis was performed. The analysis revealed the
      induction of stress-responsive genes such as those encoding heat shock proteins
      and trehalose biosynthetic enzymes in YK60-1. Furthermore, nontargeting
      metabolome analysis showed that YK60-1 accumulated more trehalose, a metabolite
      that contributes to stress tolerance in yeast, than MT8-1. In conclusion, S.
      cerevisiae MT8-1 acquired thermotolerance by induction of specific stress
      responsive genes and enhanced intracellular trehalose levels.

PMID- 24115579
TI  - Discovery of inhibitors of the Wnt and Hedgehog signaling pathways through the
      catalytic enantioselective synthesis of an iridoid-inspired compound collection.
AB  - Cousins you can count on: An iridoid-inspired compound collection was synthesized
      efficiently by the resolution of cyclic enones in an asymmetric cycloaddition
      with azomethine ylides. The collection contained novel potent inhibitors of the
      Wnt and Hedgehog signaling pathways. 

PMID- 24115580
TI  - Sustained effects of atmospheric [CO2] and nitrogen availability on forest soil
      CO2 efflux.
AB  - Soil CO2 efflux (Fsoil ) is the largest source of carbon from forests and
      reflects primary productivity as well as how carbon is allocated within forest
      ecosystems. Through early stages of stand development, both elevated [CO2] and
      availability of soil nitrogen (N; sum of mineralization, deposition, and
      fixation) have been shown to increase gross primary productivity, but the long
      term effects of these factors on Fsoil are less clear. Expanding on previous
      studies at the Duke Free-Air CO2 Enrichment (FACE) site, we quantified the
      effects of elevated [CO2] and N fertilization on Fsoil using daily measurements
      from automated chambers over 10 years. Consistent with previous results, compared
      to ambient unfertilized plots, annual Fsoil increased under elevated [CO2] (ca.
      17%) and decreased with N (ca. 21%). N fertilization under elevated [CO2] reduced
      Fsoil to values similar to untreated plots. Over the study period, base
      respiration rates increased with leaf productivity, but declined after
      productivity saturated. Despite treatment-induced differences in aboveground
      biomass, soil temperature and water content were similar among treatments.
      Interannually, low soil water content decreased annual Fsoil from potential
      values - estimated based on temperature alone assuming nonlimiting soil water
      content - by ca. 0.7% per 1.0% reduction in relative extractable water. This
      effect was only slightly ameliorated by elevated [CO2]. Variability in soil N
      availability among plots accounted for the spatial variability in Fsoil , showing
      a decrease of ca. 114 g C m(-2) yr(-1) per 1 g m(-2) increase in soil N
      availability, with consistently higher Fsoil in elevated [CO2] plots ca. 127 g C
      per 100 ppm [CO2] over the +200 ppm enrichment. Altogether, reflecting increased
      belowground carbon partitioning in response to greater plant nutritional needs,
      the effects of elevated [CO2] and N fertilization on Fsoil in this stand are
      sustained beyond the early stages of stand development and through stabilization
      of annual foliage production.

PMID- 24115581
TI  - Cell-free preparation of functional and triggerable giant proteoliposomes.
AB  - Heat, we leak: We express a membrane protein outside well-defined giant liposomes
      obtained by gravity-transferred sucrose-in-oil droplets into a cell-free,
      reconstituted expression system. We show that the presence of the liposome is
      necessary during expression for efficient protein insertion into the membrane and
      that temperature can trigger the resulting membrane function. 

PMID- 24115582
TI  - Evaluation of matrix effects in the analysis of volatile organic compounds in
      whole blood with solid-phase microextraction.
AB  - The complexity and matrix variability of biological samples requires an accurate
      evaluation of matrix effects. The dilution of the biological sample is the
      simplest way to reduce or avoid the matrix effect. In the present study, a set of
      volatile organic compounds with different volatilities was used to assess the
      effect of the dilution of blood samples on the extraction efficiency by headspace
      solid-phase microextraction. It was found that there was a significant matrix
      effect but that this effect differs significantly depending on the volatility of
      the compound. A 1:2 (blood/water) dilution was enough to allow quantitative
      recoveries of those compounds with boiling points <100 degrees C. For compounds
      with boiling points between 100 and 150 degrees C, the matrix effect was stronger
      and a 1:5 dilution was required. The dilution of blood samples proved to be
      inefficient for quantitative recovery of compounds with boiling points >150
      degrees C. A 1:5 dilution of the sample allowed detection limits in the range of
      nanogram per liter to be obtained. This was sufficient to detect the main
      volatile compounds present in blood and contamination after exposure. 

PMID- 24115583
TI  - Rescue of amyotrophic lateral sclerosis phenotype in a mouse model by intravenous
      AAV9-ADAR2 delivery to motor neurons.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron
      disease, and the lack of effective therapy results in inevitable death within a
      few years of onset. Failure of GluA2 RNA editing resulting from downregulation of
      the RNA-editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) occurs in the
      majority of ALS cases and causes the death of motor neurons via a Ca(2+) 
      permeable AMPA receptor-mediated mechanism. Here, we explored the possibility of
      gene therapy for ALS by upregulating ADAR2 in mouse motor neurons using an adeno
      associated virus serotype 9 (AAV9) vector that provides gene delivery to a wide
      array of central neurons after peripheral administration. A single intravenous
      injection of AAV9-ADAR2 in conditional ADAR2 knockout mice (AR2), which comprise
      a mechanistic mouse model of sporadic ALS, caused expression of exogenous ADAR2
      in the central neurons and effectively prevented progressive motor dysfunction.
      Notably, AAV9-ADAR2 rescued the motor neurons of AR2 mice from death by
      normalizing TDP-43 expression. This AAV9-mediated ADAR2 gene delivery may
      therefore enable the development of a gene therapy for ALS.

PMID- 24115584
TI  - Evaluation of resveratrol and N-acetylcysteine for cancer chemoprevention in a
      Fanconi anemia murine model.
AB  - Fanconi anemia (FA) patients suffer from progressive bone marrow failure and
      often develop cancers. Previous studies showed that antioxidants tempol and
      resveratrol (RV) delayed tumor onset and reduced hematologic defects in FA murine
      models, respectively. Here we tested whether antioxidants N-acetylcysteine (NAC)
      or RV could delay cancer in tumor prone Fancd2(-/-) /Trp53(+/-) mice. Unlike
      tempol, neither compound had any significant chemopreventive effect in this
      model. We conclude that not all anti-oxidants are chemopreventive in FA. In
      addition, when given to Fancd2(-/-) mice, NAC helped maintain Fancd2(-/-) KSL
      cells in quiescence while tempol did not. The mechanisms behind the different
      actions of these antioxidants await further investigation.

PMID- 24115585
TI  - Evidence for key enzymatic controls on metabolism of Arctic river organic matter.
AB  - Permafrost thaw in the Arctic driven by climate change is mobilizing ancient
      terrigenous organic carbon (OC) into fluvial networks. Understanding the controls
      on metabolism of this OC is imperative for assessing its role with respect to
      climate feedbacks. In this study, we examined the effect of inorganic nutrient
      supply and dissolved organic matter (DOM) composition on aquatic extracellular
      enzyme activities (EEAs) in waters draining the Kolyma River Basin (Siberia),
      including permafrost-derived OC. Reducing the phenolic content of the DOM pool
      resulted in dramatic increases in hydrolase EEAs (e.g., phosphatase activity
      increased >28-fold) supporting the idea that high concentrations of polyphenolic
      compounds in DOM (e.g., plant structural tissues) inhibit enzyme synthesis or
      activity, limiting OC degradation. EEAs were significantly more responsive to
      inorganic nutrient additions only after phenolic inhibition was experimentally
      removed. In controlled mixtures of modern OC and thawed permafrost endmember OC
      sources, respiration rates per unit dissolved OC were 1.3-1.6 times higher in
      waters containing ancient carbon, suggesting that permafrost-derived OC was more
      available for microbial mineralization. In addition, waters containing ancient
      permafrost-derived OC supported elevated phosphatase and glucosidase activities.
      Based on these combined results, we propose that both composition and nutrient
      availability regulate DOM metabolism in Arctic aquatic ecosystems. Our empirical
      findings are incorporated into a mechanistic conceptual model highlighting two
      key enzymatic processes in the mineralization of riverine OM: (i) the role of
      phenol oxidase activity in reducing inhibitory phenolic compounds and (ii) the
      role of phosphatase in mobilizing organic P. Permafrost-derived DOM degradation
      was less constrained by this initial 'phenolic-OM' inhibition; thus, informing
      reports of high biological availability of ancient, permafrost-derived DOM with
      clear ramifications for its metabolism in fluvial networks and feedbacks to
      climate. 

PMID- 24115586
TI  - Non-transcriptional interactions of Hox proteins: inventory, facts, and future
      directions.
AB  - Hox proteins are conserved homeodomain transcription factors involved in the
      control of embryo patterning, organ development, and cell differentiation during
      animal development and adult life. Although recognizably active in gene
      regulation, accumulating reports support that Hox proteins are also active in
      controlling other molecular processes like mRNA translation, DNA repair,
      initiation of DNA replication, and possibly modulation of signal transduction.
      Here we review experimental evidence as well as databases entries indicative of
      non-transcriptional activities of Hox proteins.

PMID- 24115587
TI  - Hepatocyte nuclear factor-1beta is not a specific marker of clear cell carcinoma
      in serous effusions.
AB  - BACKGROUND: The transcription factor hepatocyte nuclear factor-1beta (HNF1beta)
      has been reported to be a specific clear cell carcinoma marker, but its role in
      the diagnosis of serous effusions is largely unexplored. The objective of this
      study was to assess the diagnostic role of 2 commercial antibodies against
      HNF1beta in effusion specimens. METHODS: Effusions (n = 101), consisting of 43
      ovarian adenocarcinomas (26 serous, 14 clear cell, 3 endometrioid), 37 nonovarian
      adenocarcinomas, 10 malignant mesotheliomas, 2 nonepithelial cancers, and 9
      reactive specimens, were immunostained using antibodies from Santa Cruz
      Biotechnology Inc (Santa Cruz, Calif) and Atlas Antibodies AB (Stockholm,
      Sweden). RESULTS: Use of the Santa Cruz antibody was associated with cytoplasmic
      or background staining in some specimens, whereas distinct staining with minimal
      background was observed using the Atlas antibody. The Santa Cruz antibody
      performed better in differentiating clear cell carcinoma from serous ovarian
      carcinoma and breast carcinoma, whereas staining was consistently negative in
      benign and malignant mesotheliomas using both antibodies. Distinct nuclear
      expression of HNF1beta was observed in lung and gastrointestinal carcinomas, most
      often using the Atlas antibody. CONCLUSIONS: The HNF1beta antibody from Atlas
      performed better than its counterpart from Santa Cruz in terms of staining
      quality, but was less specific for clear cell carcinoma. Although HNF1beta may be
      of diagnostic value in differentiating clear cell from serous carcinoma in cases
      with proven genital origin, the role of this marker is questionable in the
      differential diagnosis between the former tumors and adenocarcinomas of other
      origin, particularly in the setting of metastasis from an unknown primary tumor.

PMID- 24115588
TI  - A glance at achievements in the coupling of headspace and direct immersion single
      drop microextraction with chromatographic techniques.
AB  - The present article offers a glance at achievements in single-drop
      microextraction(SDME), with a focus on the two most commonly used modes of this
      technique: headspace and direct immersion. Factors affecting SDME, such as the pH
      and ionic strength of the sample solution, the stirring rate, and the extraction
      time are briefly summarized. The requirements for the acceptor phase and the
      influence of the sampling temperature are presented. In addition, the potential
      of the application of microwave and ultrasonic energy in SDME is also discussed.
      Examples of the application of the headspace and direct immersion modes of SDME
      are given in a table as additional Supporting Information. 

PMID- 24115590
TI  - Catastrophizing mediates the relationship between fear of pain and preference for
      elective caesarean section.
AB  - BACKGROUND: Fear of childbirth is associated with preference for an elective
      caesarean section (ECS); however, the role of fear of pain and pain
      catastrophizing (the tendency to predict the worst case scenario) have not been
      investigated. The aim of current study was to investigate whether fear of pain
      and catastrophizing were independent predictors of preference for ECS. We
      hypothesized that pain catastrophizing and negative affectivity would mediate the
      relationship between fear of pain and preference for ECS. METHODS: Three hundred
      pregnant women between 4 and 36 weeks of gestation were asked to indicate whether
      they would prefer to deliver their baby through an ECS or a vaginal delivery.
      They were also asked to complete a battery of questionnaires assessing
      demographic details, mood, fear of childbirth, fear of pain and catastrophizing.
      Consistent with cultural norms, more than half of the women preferred an ECS
      (58%). RESULTS: Women who chose ECS were more likely to seek private obstetric
      care, have had a previous caesarean section and have higher levels of fear of
      childbirth, fear of pain, more catastrophic cognitions and lower mood.
      Catastrophizing, but not negative affectivity, mediated the relationship between
      fear of pain and preference for ECS, as predicted. CONCLUSIONS: Fear of both
      childbirth and pain were both independent predictors of preference for ECS.
      Catastrophizing mediated the relationship between fear of pain and preference for
      ECS. Interventions that target these factors may reduce the trend towards
      increasing numbers of ECS internationally.

PMID- 24115589
TI  - The association between childhood sexual and physical abuse with incident adult
      severe obesity across 13 years of the National Longitudinal Study of Adolescent
      Health.
AB  - BACKGROUND: Severe obesity has increased, yet childhood antecedents of adult
      severe obesity are not well understood. OBJECTIVE: Estimate adult-onset severe
      obesity risk in individuals with history of childhood physical and/or sexual
      abuse compared with those who did not report abuse. METHODS: Longitudinal
      analysis of participants from the US National Longitudinal Study of Adolescent
      Health (n = 10,774) wave II (1996; aged 12-22 years) followed through wave IV
      (2008-2009; aged 24-34 years). New cases of adult-onset severe obesity (body mass
      index [BMI] >= 40 kg/m2 using measured height and weight) in individuals followed
      over 13 years who were not severely obese during adolescence (BMI <120% of 95th
      percentile Centers for Disease Control and Prevention National Center for Health
      Statistics growth curves). RESULTS: The combined occurrence of self-reported
      sexual and physical abuse during childhood was associated with an increased risk
      of incident severe obesity in adulthood in non-minority females (hazard ratio
      [HR; 95% Confidence Interval] = 2.5; 1.3, 4.8) and males (HR = 3.6; 1.5, 8.5)
      compared with individuals with no history of abuse. CONCLUSION: In addition to
      other social and emotional risks, exposure to sexual and physical abuse during
      childhood may increase risk of severe obesity later in life. Consideration of the
      confluence of childhood abuse might be considered as part of preventive and
      therapeutic approaches to address severe obesity.

PMID- 24115591
TI  - Gold nanoparticle 3D-DNA building blocks: high purity preparation and use for
      modular access to nanoparticle assemblies.
AB  - Using highly functional 'building-blocks' of AuNPs mono-conjugated to three
      dimensional DNA 'rung' structures, both discrete and extended linear assemblies
      are controllably prepared via addition of various templating backbone strands.
      This unique approach presents a facile alternative to other methods of AuNP
      organization through DNA, and has potential utility in the fields of
      nanophotonics and nanoelectronics. 

PMID- 24115592
TI  - Rescuing auxotrophic microorganisms with nonenzymatic chemistry.

PMID- 24115593
TI  - p38 Signaling in titanium particle-induced MMP-2 secretion and activation in
      differentiating MC3T3-E1 cells.
AB  - The periprosthetic osteolysis induced by wear particles contributes to aseptic
      loosening after joint arthroplasty. The molecular mechanism underlying osteolysis
      remains to be described. In this study, cultured MC3T3-E1 cells were incubated
      with titanium particles. We investigated the role of p38 mitogen-activated
      protein kinase in the expression of MMP-2 in response to wear particles. Our
      results demonstrated MC3T3-E1 cells exposed to titanium particles had
      significantly increased levels of MMP-2 and MT1-MMP mRNA, whereas the TIMP-2 mRNA
      level was unchanged. In MC3T3-E1 cells, the protein expression of MMP-2, MT1-MMP,
      and active p38 was also elevated after titanium particle exposure, as detected by
      Western blot and Biotrak activity analyses. Inhibition studies showed that the
      specific p38 inhibitor SB203580 completely abrogated the increase in MMP-2 and
      MT1-MMP production induced by the titanium particles. Moreover, our results
      revealed that conditioned media-stimulated osteoclast formation was related to
      the MMP-2 activity of osteoblasts that were challenged with Ti particles. This
      study demonstrated that p38 signaling is required for MMP-2 activity in
      osteoblasts under wear particle-induced conditions. MMP-2 could act as a
      catabolic element or a proinflammatory factor contributing to periprosthetic
      osteolysis. Therefore, the p38 pathway and MMP-2 may play a critical role in the
      development of aseptic loosening.

PMID- 24115595
TI  - p35 promotes the differentiation of amacrine cell subtype in the zebrafish retina
      under the regulation of egr1.
AB  - BACKGROUND: Early growth response 1 (egr1) is a transcription factor (TF) for
      controlling the differentiation of Parvalbumin (Parv) -expressing amacrine cells
      (ACs) in zebrafish. However, the downstream factors of this process have not been
      identified. The purpose of this study was to investigate the role of p35, a
      neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) and a known in
      vitro target of egr1, in the differentiation of these ACs. RESULTS: In the p35
      knockdown retinas, Parv+ but not islet1+ ACs were specifically reduced. This
      phenotype was highly similar to that in the Egr1-knockdown retinas. Furthermore,
      p35 expression was reduced in the Egr1-knockdown retinas, particularly in the AC
      region; while egr1 was only modestly reduced in this region in the p35-knockdown
      retinas. CONCLUSIONS: p35 likely acts downstream of egr1 to control the
      differentiation of Parv+ ACs.

PMID- 24115596
TI  - Bone formation in adipose-derived stem cells isolated from elderly patients with
      osteoporosis: a preliminary study.
AB  - We have explored the osteogenic potency of adipose-derived stem cells from
      osteoporotic patients (opASCs). opASCs were osteogenically induced in vitro with
      collagen I hydrogel or in culture plate. Detection of alkaline phosphatase
      (ALPase) and cell mineralisation, and quantitative RT-PCR of collagen I,
      osteocalcin and bone sialoprotein were undertaken. Proliferation and morphology
      studies were also performed. After 14 days, opASCs-collagen I hydrogel composite
      was implanted into nude mice for 4 weeks prior to radiographic and histological
      analysis. Staining of ALPase and cell mineralisation was strongly positive in
      opASCs. Fibroblast-like opASCs induced with collagen I hydrogel were evenly
      distributed and proliferated at a higher rate than in culture plates, showing
      similar growth curves for both genders. Expression of ALPase activity, cell
      mineralisation and osteogenic specific genes were higher in opASCs with collagen
      I hydrogel (male samples had better osteogenicity than female samples) than in
      culture plates. After implantation for 4 weeks, radiopaque area signifying new
      bone tissue was observed in opASCs-collagen I hydrogel composite, with no donor
      gender differences. Thus opASCs with collagen I hydrogel have adequate osteogenic
      potency and offer new possibilities for osteoporosis-related bone tissue
      engineering in male and female patients. 

PMID- 24115594
TI  - The emerging role of triple helices in RNA biology.
AB  - The ability of RNA to form sophisticated secondary and tertiary structures
      enables it to perform a wide variety of cellular functions. One tertiary
      structure, the RNA triple helix, was first observed in vitro over 50 years ago,
      but biological activities for triple helices are only beginning to be
      appreciated. The recent determination of several RNA structures has implicated
      triple helices in distinct biological functions. For example, the SAM-II
      riboswitch forms a triple helix that creates a highly specific binding pocket for
      S-adenosylmethionine. In addition, a triple helix in the conserved pseudoknot
      domain of the telomerase-associated RNA TER is essential for telomerase activity.
      A viral RNA cis-acting RNA element called the ENE contributes to the nuclear
      stability of a viral noncoding RNA by forming a triple helix with the poly(A)
      tail. Finally, a cellular noncoding RNA, MALAT1, includes a triple helix at its
      3'-end that contributes to RNA stability, but surprisingly also supports
      translation. These examples highlight the diverse roles that RNA triple helices
      play in biology. Moreover, the dissection of triple helix mechanisms has the
      potential to uncover fundamental pathways in cell biology.

PMID- 24115597
TI  - Fully automated tool to identify the aorta and compute flow using phase-contrast
      MRI: validation and application in a large population based study.
AB  - PURPOSE: To assess if fully automated localization of the aorta can be achieved
      using phase contrast (PC) MR images. MATERIALS AND METHODS: PC cardiac-gated MR
      images were obtained as part of a large population-based study. A fully automated
      process using the Hough transform was developed to localize the ascending aorta
      (AAo) and descending aorta (DAo). The study was designed to validate this
      technique by determining: (i) its performance in localizing the AAo and DAo; (ii)
      its accuracy in generating AAo flow volume and DAo flow volume; and (iii) its
      robustness on studies with pathological abnormalities or imaging artifacts.
      RESULTS: The algorithm was applied successfully on 1884 participants. In the
      randomly selected 50-study validation set, linear regression shows an excellent
      correlation between the automated (A) and manual (M) methods for AAo flow (r =
      0.99) and DAo flow (r = 0.99). Bland-Altman difference analysis demonstrates
      strong agreement with minimal bias for: AAo flow (mean difference [A-M] = 0.47 +/
      2.53 mL), and DAo flow (mean difference [A-M] = 1.74 +/- 2.47 mL). CONCLUSION: A
      robust fully automated tool to localize the aorta and provide flow volume
      measurements on phase contrast MRI was validated on a large population-based
      study.

PMID- 24115598
TI  - Mycobacterial phenolic glycolipids with a simplified lipid aglycone modulate
      cytokine levels through Toll-like receptor 2.
AB  - Phenolic glycolipids (PGLs) are virulence factors present in the cell walls of
      many pathogenic mycobacteria. PGLs have been implicated in various aspects of
      mycobacterial disease, but there are limited structure-activity data available
      for these molecules. We report here the preparation of seven synthetic PGL
      analogues, differing from the native compounds in the replacement of the complex
      phenolic lipid moiety with a p-methoxyphenyl group. The ability of these
      compounds to stimulate or inhibit the production of cytokines (TNF-alpha, IL
      1beta, IL-6, MCP-1) and nitric oxide (NO) was then evaluated by ELISA-based
      assays. None of the compounds stimulated the production of these biological
      signalling molecules. In contrast, they each displayed concentration-dependent
      inhibitory activity, related to the methylation pattern of the molecule and
      mediated by Toll-like receptor 2. Additional studies revealed that native PGL-I
      from Mycobacterium leprae and a synthetic PGL-I analogue containing a simplified
      lipid domain had enhanced inhibitory activities relative to the corresponding
      analogues containing the p-methoxyphenyl aglycone; however, the natural lipid
      phenolthiocerol was only weakly active. These studies reveal that synthetic
      molecules of this type can be used as probes for PGL function. Moreover, their
      ease of synthesis relative to the natural glycolipids, as well as their more
      favourable aqueous solubility, should allow for more thorough structure-activity
      relationship studies. 

PMID- 24115599
TI  - Will retransplantation be the norm for pediatric recipients with ambitions for
      grandparenthood?

PMID- 24115600
TI  - Counseling parents before prenatal diagnosis: do we need to say more about the
      sex chromosome aneuploidies?
AB  - Sex chromosome trisomies (SCT), an extra X chromosome in females (triple X, XXX),
      males with an extra X chromosome (Klinefelter syndrome, XXY) or an extra Y
      chromosome (XYY) occur because of errors during meiosis and are relatively
      frequent in humans. Their identification has never been the goal of prenatal
      diagnosis (PD) but they almost never escape detection by any of the methods
      commonly in use. Despite recommendations and guide-lines which emphasize the
      importance of structured counseling before and after PD, most women remain
      unaware that testing for serious genetic abnormalities is more likely to uncover
      these trisomies. With the increasing use of PD more and more prospective parents
      receive a diagnosis of sex chromosome trisomies and are faced with the dilemma of
      whether to terminate the pregnancy or to carry it to term. Despite the dramatic
      and emotionally devastating consequences of having to make such a decision, they
      have little opportunity to consider in advance the possible outcomes of such a
      pregnancy and, rather than relying on their own feelings and judgements, are
      forced to depend on the advice of counseling professionals who may or may not
      themselves be fully aware of what having an extra sex chromosome can mean to the
      development of a child. We address here the principles of reproductive autonomy
      together with an analysis of the major issues that ought to be discussed with the
      parents before a PD is carried out in order to minimize detrimental effects
      caused by this unexpected finding.

PMID- 24115601
TI  - Identification and quantification of 5,6,7,8-tetrahydro-2-(2
      phenylethyl)chromones in Chinese eaglewood by HPLC with diode array detection and
      MS.
AB  - A sensitive and reliable HPLC coupled with diode array detection and MS method
      was developed and validated for the first time to simultaneously identify and
      quantify eight characteristic 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones
      (THPECs) in Chinese eaglewood. Chromatographic separation was performed on a
      Zorbax SB C18 column with a gradient of acetonitrile/0.1% formic acid/water as
      the mobile phase. The MS fragmentation behavior of THPECs was characterized as
      the successive neutral loss of two molecules of H2 O ([M+H-18-18](+) ) and then
      two molecules of CO ([M+H-18-18-28-28](+) ), which could be used to differentiate
      Chinese eaglewood from counterfeits. Validation of the developed analytical
      method showed good linearity, satisfactory precision, and good recovery. The
      established method was successfully applied to the simultaneous determination of
      eight THPECs in ten batches of Chinese eaglewood, which could be used as a tool
      for the quality control of Chinese eaglewood. 

PMID- 24115602
TI  - Differential proteomic profiling in human spermatozoa that did or did not result
      in pregnancy via IVF and AID.
AB  - PURPOSE: To identify biochemical markers in men with idiopathic infertility and
      normal sperm counts. EXPERIMENTAL DESIGN: We obtained proteomic profiling
      proteins in human spermatozoa following successful or unsuccessful pregnancy via
      assisted reproductive technology (ART) using 6-plex tandem mass tag (TMT)
      isobaric mass spectrometry. Our study design consisted of two groups: 1. The
      semen of 6 men whose sperm resulted in a clinical pregnancy following ART and 6
      men whose semen did not result in a clinical pregnancy following ART. The results
      of differentiated mass spectrometry were validated by Western blotting. RESULTS
      AND DISCUSSION: A total of 2,045 proteins were detected in our cohort. 21
      proteins were found to be differentially expressed (>1.2-fold) in men whose sperm
      resulted in a clinical pregnancy and those that did not. Using the results of
      bioinformatics analysis and Western Blotting, three proteins (A2LD1, ATP1B3 and
      FBXO2) were shown to have the same differential pattern (p<0.05) that was
      observed in the mass spectrometry analysis. CONCLUSIONS AND CLINICAL RELEVANCE:
      Proteomics may help identity a select cohort of men with abnormal semen
      parameters and aide infertility diagnoses.

PMID- 24115603
TI  - The origin and evolution of six miniature inverted-repeat transposable elements
      in Bombyx mori and Rhodnius prolixus.
AB  - Miniature inverted-repeat transposable elements (MITEs) are a specific group of
      nonautonomous DNA transposons, and they are distributed in a wide range of hosts.
      However, the origin and evolutionary history of MITEs in eukaryotic genomes
      remain unclear. In this study, six MITEs were identified in the silkworm (Bombyx
      mori). Five elements are grouped into four known superfamilies of DNA
      transposons, and one represents a novel class of MITEs. Unexpectedly, six similar
      MITEs are also present in the triatomine bug (Rhodnius prolixus) that diverged
      from the common ancestor with the silkworm about 370 Ma. However, they show
      different lengths in two species, suggesting that they are different derivatives
      of progenitor transposons. Three direct progenitor transposons (Sola1,
      hobo/Ac/Tam [hAT], and Ginger2) are also identified in some other organisms, and
      several lines of evidence suggested that these autonomous elements might have
      been independently and horizontally transferred into their hosts. Furthermore, it
      is speculated that the twisted-wing parasites may be the candidate vectors for
      these horizontal transfers. The data presented in this study provide some new
      insights into the origin and evolutionary history of MITEs in the silkworm and
      triatomine bug. 

PMID- 24115604
TI  - On the need for mechanistic models in computational genomics and metagenomics.
AB  - Computational genomics is now generating very large volumes of data that have the
      potential to be used to address important questions in both basic biology and
      biomedicine. Addressing these important biological questions becomes possible
      when mechanistic models rooted in biochemistry and evolutionary/population
      genetic processes are developed, instead of fitting data to off-the-shelf
      statistical distributions that do not enable mechanistic inference. Three
      examples are presented, the first involving ecological processes inferred from
      metagenomic data, the second involving mechanisms of gene regulation rooted in
      protein-DNA interactions with consideration of DNA structure, and the third
      involving existing models for the retention of duplicate genes that enables
      prediction of evolutionary mechanisms. This description of mechanistic models is
      generalized toward future developments in computational genomics and the need for
      biological mechanisms and processes in biological models. 

PMID- 24115605
TI  - Imaging the cadavers being dissected does not appear to improve the gross anatomy
      dissection experience.

PMID- 24115606
TI  - Immobilization of aluminum borohydride hexammoniate in a nanoporous polymer
      stabilizer for enhanced chemical hydrogen storage.

PMID- 24115607
TI  - Soil microbial and nutrient responses to 7 years of seasonally altered
      precipitation in a Chihuahuan Desert grassland.
AB  - Soil microbial communities in Chihuahuan Desert grasslands generally experience
      highly variable spatiotemporal rainfall patterns. Changes in precipitation
      regimes can affect belowground ecosystem processes such as decomposition and
      nutrient cycling by altering soil microbial community structure and function. The
      objective of this study was to determine if increased seasonal precipitation
      frequency and magnitude over a 7-year period would generate a persistent shift in
      microbial community characteristics and soil nutrient availability. We
      supplemented natural rainfall with large events (one/winter and three/summer) to
      simulate increased precipitation based on climate model predictions for this
      region. We observed a 2-year delay in microbial responses to supplemental
      precipitation treatments. In years 3-5, higher microbial biomass, arbuscular
      mycorrhizae abundance, and soil enzyme C and P acquisition activities were
      observed in the supplemental water plots even during extended drought periods. In
      years 5-7, available soil P was consistently lower in the watered plots compared
      to control plots. Shifts in soil P corresponded to higher fungal abundances,
      microbial C utilization activity, and soil pH. This study demonstrated that 25%
      shifts in seasonal rainfall can significantly influence soil microbial and
      nutrient properties, which in turn may have long-term effects on nutrient cycling
      and plant P uptake in this desert grassland. 

PMID- 24115608
TI  - Chiral Bronsted acid mediated glycosylation with recognition of alcohol
      chirality.

PMID- 24115609
TI  - A novel mutation in protein C gene (PROC) causing severe phenotype in neonatal
      period.
AB  - Homozygous protein C deficiency is among rare causes of thrombophilia. Herein, we
      present a neonate with purpura fulminans, disseminated intravascular coagulation
      and severe intracranial hemorrhage who was found to have plasma protein C level
      of 4%. The molecular work-up revealed a novel homozygous mutation of T903C (amino
      acid position Leu 270 Pro) located in a catalytic domain region of PROC gene.
      Asymptomatic course in patients with low but measurable levels of protein C
      levels has been reported, which is different than observed in our patient who had
      a very severe course despite plasma protein C level of 4%.

PMID- 24115610
TI  - The presence of antibiotic-resistant nosocomial pathogens in endotracheal tube
      biofilms and corresponding surveillance cultures.
AB  - Mechanically ventilated patients often develop ventilator-associated pneumonia
      (VAP). Soon after intubation, a mixed biofilm harboring microbial pathogens is
      formed on the endotracheal tube (ET). It is believed that this biofilm
      contributes to the development of VAP. Unfortunately, the causative agent is
      often not known at the time VAP is suspected, and early therapy often relies on
      the identification of surveillance cultures (SC). It is thus important to know
      whether these SC can predict the microbial flora in ET biofilms. In this study,
      we compare the presence of a number of antibiotic-resistant nosocomial bacteria
      (Enterobacter aerogenes, Escherichia coli, Micrococcus luteus, Pseudomonas
      aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis) and of Candida
      albicans in cultures from ET biofilms and SC (i.e. sputum samples, nose swabs,
      and throat swabs) of 20 mechanically ventilated patients. Our data indicate that
      there is a good correlation between the presence of (antibiotic-resistant)
      pathogens in ET biofilms and SC. 

PMID- 24115611
TI  - Nickel-catalyzed sonogashira reactions of non-activated secondary alkyl bromides
      and iodides.
AB  - A nicked reaction: The title reaction of terminal alkynes with non-activated
      secondary alkyl iodides and bromides was accomplished for the first time. This
      reaction provides a new and practical approach for the synthesis of substituted
      alkynes (see scheme; cod=cyclo-1,5-octadiene). 

PMID- 24115612
TI  - Dickeya ecology, environment sensing and regulation of virulence programme.
AB  - The pectinolytic Dickeya spp. are soft-rot Gram-negative bacteria that cause
      severe disease in a wide range of plant species. In recent years, there has been
      an increase in the damage caused by Dickeya in potato crops in Europe. Soft-rot
      symptoms are due to the production and secretion of degradative enzymes that
      destroy the plant cell wall. However, an efficient colonization of the host plant
      requires many additional bacterial factors, including elements in the early
      stages allowing for the adhesion and penetration of the bacteria in the plant and
      different elements in the intermediate stages, involved in the adaptation to the
      new growth conditions encountered in the host. Dickeya pathogenicity is clearly a
      multifactorial process, and successful infection by these bacteria requires a
      temporal coordination of survival and virulence gene expression. This involves
      the ancestral nucleoid-associated proteins, Fis and H-NS, and modifications of
      DNA topology, as well as various specific regulatory systems, including a new
      quorum-sensing pathway and regulators that sense the bacterial metabolic status
      or environmental stresses. This review presents new information concerning the
      ecology of Dickeya and the strategies used by this bacterium to coordinate its
      survival and virulence programmes during infection. 

PMID- 24115613
TI  - Congruence between mcy based genetic type and microcystin composition within the
      populations of toxic Microcystis in a Plateau Lake, China.
AB  - Genetic diversity and differential microcystin contributions within the
      populations of toxic Microcystis in freshwater ecosystems have not been fully
      discussed. To illustrate this issue, we sequenced clone libraries of the first
      adenylation domain of mcyB (mcyBA1) from Microcystis populations in a plateau
      lake. Phylogenetic analysis revealed two divergent groups of McyBA1 with two
      closely related subgroups within Group I. While neutral evolution was indicated
      on the whole McyBA1 domain, 1-5 recombination breakpoints and several codons
      under positive or negative selections were found. Significant seasonal changes of
      McyBA1 diversity were observed. Group I composed the major proportion of the
      McyBA1 pool throughout the growing season in the whole lake. Group IA and Group
      II denominated Microcystis strains isolated from this lake were characterized by
      preference production of microcystin-RR (62-85%) and microcystin-LR (> 98%)
      respectively. We detected the intracellular microcystins in lake water and
      microcystin-RR was a main variant (mostly > 50%). In summary, McyBA1 subgroups
      were dominant within the population of toxic Microcystis and contributed the
      predominance of microcystin-RR in the lake. The differences of substrate
      preference in microcystin biosynthesis among groups were caused by neutral
      evolution and homologous recombination.

PMID- 24115615
TI  - The lowering of external pH in confined environments by thermo-acidophilic algae
      (class: Cyanidiophyceae).
AB  - The unicellular, asexual thermo-acidophilic algae of the class Cyanidiophyceae,
      order Cyanidiales (the 'cyanidia') include only three genera, walled Cyanidium
      and Galdieria, and 'naked' Cyanidioschyzon, names based on morphological and
      cytological characters. Most species and strains of this class live in acid hot
      springs or acid soils or steam vents associated with these springs at pH 0.5 to ~
      4.0 at temperatures of ~ 38-56  degrees C. No other phototrophs live in this
      combination of factors in these habitats, except for a small overlap with other
      acidophilic algae at the highest pH and the lowest temperature. The optimum pH
      for growth of the 'cyanidia' in this study was ~ 2.3. Galdieria-like walled cells
      of Cyanidioschyzon and naked Cyanidioschyzon cells were exposed in culture to
      higher pH conditions of 6.0, 5.5 and 5.0 in confined, illuminated environments
      (cotton plugged flasks). The subsequent acidification of the medium towards or to
      2.3 occurred as growth and biomass increased. There was a direct correlation with
      final biomass (Chl a) and lower pH. All eight strains isolated from Yellowstone
      acidic conditions were able to lower the supra-optimal pH of their medium, while
      only two from other continents and none of the three from Japan were competent.
      It is probable that the ability to lower pH to an optimal level has survival
      value in some niches in natural habitats.

PMID- 24115616
TI  - Growth kinetics and energetics of a deep-sea hyperthermophilic methanogen under
      varying environmental conditions.
AB  - A hyperthermophilic deep-sea methanogen, Methanocaldococcus strain JH146, was
      isolated from 26 degrees C hydrothermal fluid at Axial Volcano to model high
      temperature methanogenesis in the subseafloor. Emphasis was placed on defining
      growth kinetics, cell yields and growth energy demand (GE) across a range of
      conditions. The organism uses H2 and CO2 as its sole carbon and energy sources.
      At various temperatures, pHs, and chlorinities, its growth rates and cell yields
      co-varied while GE remained uniform at 1.69 * 10(-11) J cell(-1)s(-1) +/- 0.68 *
      10(-11) J cell(-1)s(-1) (s.d., n = 23). An exception was at superoptimal growth
      temperatures where GE increased to 7.25 * 10(-11) J cell(-1)s(-1) presumably due
      to heat shock. GE also increased from 5.1 * 10(-12) J cell(-1)s(-1) to 7.61 * 10(
      11) J cell(-1)s(-1) as NH4 (+) concentrations decreased from 9.4 mM to 0.14 mM.
      JH146 did not fix N2 or assimilate NO3 (-), lacked the N2-fixing (cluster II)
      nifH gene, and became nitrogen limited below 0.14 mM NH4Cl. Nitrogen availability
      may impact growth in situ since ammonia concentrations at Axial Volcano are < 18
      MUM. Our approach contributes to refining bioenergetic and carbon flux models for
      methanogens and other organisms in hydrothermal vents and other environments.

PMID- 24115617
TI  - Enrichment and isolation of acidophilic sulfate-reducing bacteria from Tinto
      River sediments.
AB  - Although some acidophilic and alkaliphilic species have been described recently,
      most of the known sulfate-reducing bacteria (SRB) grow optimally at neutral pH.
      In this study, sulfate reduction was studied with sediment samples from the
      extremely acidic Tinto River basin. Stable enrichments of SRB were obtained at pH
      4 with glycerol, methanol and hydrogen; at pH 4.5 with lactate and at pH 5.5 with
      succinate as substrates. Inhibition of sulfate reduction by organic acids below
      their pKa was observed. Cloning and sequencing of 16S rRNA gene showed that
      fermentative bacteria (Paludibacter spp., Oscillibacter spp.) and SRB
      (Thermodesulfobium spp., Desulfosporosinus spp., Desulfitobacterium spp.,
      Desulfotomaculum spp.) were co-enriched. By repeated serial dilutions and
      streaking on agar plates, four strains of SRB belonging to the Firmicutes phylum
      were obtained. Two of them show 96% 16S rRNA gene sequence similarity with
      Desulfosporosinus acidophilus, and a third one with Desulfosporosinus orientis.
      Another isolate has just 93% rRNA gene sequence similarity with the
      Desulfosporosinus/Desulfitobacterium cluster and might represent a novel species
      within a novel genus. One of the Desulfosporosinus strains was further
      investigated showing maximum growth at pH 5.5, and a pH-dependent inhibitory
      effect of organic acids and sulfide.

PMID- 24115618
TI  - New methods for the isolation and characterization of biofilm-persistent mutants
      in Pseudomonas putida.
AB  - Here we describe two new methods for the genetic characterization of bacterial
      biofilm development. First, we have designed a microtitre dish-based approach for
      high-throughput screening of Pseudomonas putida mutants showing increased biofilm
      under dispersal conditions. Using this method, nine such biofilm-persistent
      mutants, bearing transposon insertions in four loci: lapG, bifA, mvaB and dksA,
      were isolated. Second, we have developed a serial dilution-based scheme to
      monitor biofilm development and dispersal in microtitre dish wells in a simple,
      time-efficient and reproducible manner. Using this method, we showed that (i)
      mutants in bifA and dksA do not undergo starvation-induced biofilm dispersal in
      LB or minimal medium, (ii) a mvaB mutant does not disperse the biofilm in LB, but
      shows a normal dispersal response in minimal medium, and (iii) unlike the lapG
      mutant, the bifA, mvaB and dksA mutants do not show an increase in biofilm
      production. The procedures shown here are useful tools for the identification of
      previously uncharacterized biofilm-related genes and considerably simplify the
      characterization of biofilm growth phenotypes. 

PMID- 24115619
TI  - Assembly-free metagenomic analysis reveals new metabolic capabilities in surface
      ocean bacterioplankton.
AB  - Uncovering the metabolic capabilities of microbes is key to understanding global
      energy flux and nutrient transformations. Since the vast majority of
      environmental microorganisms are uncultured, metagenomics has become an important
      tool to genotype the microbial community. This study uses a recently developed
      computational method to confidently assign metagenomic reads to microbial clades
      without the requirement of metagenome assembly by comparing the evolutionary
      pattern of nucleotide sequences at non-synonymous sites between metagenomic and
      orthologous reference genes. We found evidence for new, ecologically relevant
      metabolic pathways in several lineages of surface ocean bacterioplankton using
      the Global Ocean Survey (GOS) metagenomic data, including assimilatory sulfate
      reduction and alkaline phosphatase capabilities in the alphaproteobacterial SAR11
      clade, and proteorhodopsin-like genes in the cyanobacterial genus
      Prochlorococcus. These findings raise new hypotheses about microbial roles in
      energy flux and organic matter transformation in the ocean. 

PMID- 24115620
TI  - Dissolved hydrogen and nitrogen fixation in the oligotrophic North Pacific
      Subtropical Gyre.
AB  - The production of hydrogen (H2) is an inherent component of biological dinitrogen
      (N2) fixation, and there have been several studies quantifying H2 production
      relative to N2 fixation in cultures of diazotrophs. However, conducting the
      relevant measurements for a field population is more complex as shown by this
      study of N2 fixation, H2 consumption and dissolved H2 concentrations in the
      oligotrophic North Pacific Ocean. Measurements of H2 oxidation revealed microbial
      consumption of H2 was equivalent to 1-7% of ethylene produced during the
      acetylene reduction assay and 11-63% of (15)N2 assimilation on a molar scale.
      Varying abundances of Crocosphaera and Trichodesmium as revealed by nifH gene
      abundances broadly corresponded with diel changes observed in both N2 fixation
      and H2 oxidation. However, no corresponding changes were observed in the
      dissolved H2 concentrations which remained consistently supersaturated (147-560%)
      relative to atmospheric equilibrium. The results from this field study allow the
      efficiency of H2 cycling by natural populations of diazotrophs to be compared to
      cultured representatives. The findings indicate that dissolved H2 concentrations
      may depend not only on the community composition of diazotrophs but also upon
      relevant environmental parameters such as light intensity or the presence of
      other H2-metabolizing microorganisms. 

PMID- 24115614
TI  - Microbial community composition and endolith colonization at an Arctic thermal
      spring are driven by calcite precipitation.
AB  - Environmental conditions shape community composition. Arctic thermal springs
      provide an opportunity to study how environmental gradients can impose strong
      selective pressures on microbial communities and provide a continuum of niche
      opportunities. We use microscopic and molecular methods to conduct a survey of
      microbial community composition at Troll Springs on Svalbard, Norway, in the high
      Arctic. Microorganisms there exist under a wide range of environmental
      conditions: in warm water as periphyton, in moist granular materials, and in
      cold, dry rock as endoliths. Troll Springs has two distinct ecosystems, aquatic
      and terrestrial, together in close proximity, with different underlying
      environmental factors shaping each microbial community. Periphyton are entrapped
      during precipitation of calcium carbonate from the spring's waters, providing
      microbial populations that serve as precursors for the development of endolithic
      communities. This process differs from most endolith colonization, in which the
      rock predates the communities that colonize it. Community composition is
      modulated as environmental conditions change within the springs. At Troll, the
      aquatic environments show a small number of dominant operational taxonomic units
      (OTUs) that are specific to each sample. The terrestrial environments show a more
      even distribution of OTUs common to multiple samples. 

PMID- 24115622
TI  - Bacterial communities associated with Microcystis colonies differ from free
      living communities living in the same ecosystem.
AB  - The search for a better understanding of why cyanobacteria often dominate
      phytoplankton communities in eutrophic freshwater ecosystems has led to a growing
      interest in the interactions between cyanobacteria and bacteria. Against this
      background, we studied the location of bacteria within Microcystis colonies, and
      compared the structural and phylogenetic diversity of Microcystis-attached and
      free-living bacterial communities living in the same French lake, the Villerest
      reservoir. Using transmission electron microscopy, we show that most of the
      bacteria inside the colonies were located close to detrital materials that
      probably resulted from lysis of Microcystis cells. The 16S rRNA sequencing
      approach revealed a clear distinction between the attached and free-living
      communities at the levels of both their general structure and their operational
      taxonomic unit (OTU) composition. In particular, Microcystis colonies appeared to
      be depleted of Actinobacteria, but conversely enriched in Gammaproteobacteria, in
      particular when the bloom was declining. At the OTU level, a clear distinction
      was also found between attached and free-living bacteria, and new clades were
      identified among our sequences. All these findings suggest that Microcystis
      colonies constitute a distinct habitat for bacteria living in freshwater
      ecosystems, and that direct and indirect interactions (cell lysis, nutrient
      recycling, etc.) may occur between them inside these colonies. 

PMID- 24115621
TI  - Non-cyanobacterial nifH phylotypes in the North Pacific Subtropical Gyre detected
      by flow-cytometry cell sorting.
AB  - In contrast to cyanobacteria, the significance of bacteria and archaea in oceanic
      N2 fixation remains unknown, apart from the knowledge that their nitrogenase
      (nifH) genes are diverse, present in all oceans and at least occasionally
      expressed. Non-cyanobacterial nifH sequences often occur as contamination from
      reagents and other sources, complicating the detection and interpretation of
      environmental phylotypes. We amplified and sequenced partial nifH gene fragments
      directly from cell populations sorted by fluorescence activated cell sorting from
      water collected in the North Pacific Subtropical Gyre (NPSG). Sequences recovered
      (195 total) included presumed heterotrophic or photoheterotrophic non
      cyanobacterial nifH phylotypes previously unreported in the NPSG. A nifH sequence
      previously found in the South Pacific Gyre (HM210397) was exclusively recovered
      from sorted picoeukaryote populations, and was detected in water column samples
      using quantitative PCR (qPCR), with 60% of samples detected in the > 10 MUm size
      fraction in addition to the 0.2-10 MUm size fraction. A novel cluster 3-like nifH
      sequence was also recovered from discrete cell sorts and detected by qPCR in
      environmental samples. This approach enables the detection of rare nifH
      phylotypes, identifies possible associations with larger cells or particles and
      offers a possible solution for distinguishing reagent contaminants from real
      microbial community components.

PMID- 24115623
TI  - Confined aquifers as viral reservoirs.
AB  - Knowledge about viral diversity and abundance in deep groundwater reserves is
      limited. We found that the viral community inhabiting a deep confined aquifer in
      South Australia was more similar to reclaimed water communities than to the viral
      communities in the overlying unconfined aquifer community. This similarity was
      driven by high relative occurrence of the single-stranded DNA viral groups
      Circoviridae, Geminiviridae and Microviridae, which include many known plant and
      animal pathogens. These groups were present in a 1500-year-old water situated 80
      m below the surface, which suggests the potential for long-term survival and
      spread of potentially pathogenic viruses in deep, confined groundwater. Obtaining
      a broader understanding of potentially pathogenic viral communities within
      aquifers is particularly important given the ability of viruses to spread within
      groundwater ecosystems.

PMID- 24115624
TI  - Patterns and drivers of bacterial alpha- and beta-diversity across vertical
      profiles from surface to subsurface sediments.
AB  - We investigated the patterns and drivers of bacterial alpha- and beta-diversity,
      along with viral and prokaryotic abundance and the carbon production rates, in
      marine surface and subsurface sediments (down to 1 m depth) in two habitats:
      vegetated sediments (seagrass meadow) and non-vegetated sediments. Prokaryotic
      abundance and production decreased with depth in the sediment, but cell-specific
      production rates and the virus-to-prokaryote ratio increased, highlighting
      unexpectedly high activity in the subsurface. The highest diversity was observed
      in vegetated sediments. Bacterial beta-diversity between sediment horizons was
      high, and only a minor number of taxa was shared between surface and subsurface
      layers. Viruses significantly contributed to explain alpha- and beta-diversity
      patterns. Despite potential limitations due to the only use of fingerprinting
      techniques, this study indicates that the coastal subsurface host highly active
      and diversified bacterial assemblages, that subsurface cells are more active than
      expected and that viruses promote beta-diversity and stimulate bacterial
      metabolism in subsurface layers. The limited number of taxa shared between
      habitats, and between surface and subsurface sediment horizons, suggests that
      future investigations of the shallow subsurface will provide insights into the
      census of bacterial diversity, and the comprehension of the patterns and drivers
      of prokaryotic diversity in marine ecosystems.

PMID- 24115625
TI  - The effect of polyphosphate kinase gene deletion on polyhydroxyalkanoate
      accumulation and carbon metabolism in Pseudomonas putida KT2440.
AB  - The primary enzyme involved in polyphosphate (polyP) synthesis, polyP kinase
      (ppk), has been deleted in Pseudomonas putida KT2440. This has resulted in a
      threefold to sixfold reduction in polyhydroxyalkanoate (PHA) accumulation
      compared with the wild type under conditions of nitrogen limitation, with either
      temperature or oxidative (H2O2) stress, when grown on glucose. The accumulation
      of PHA by Deltappk mutant was the same as the wild type under nitrogen-limiting
      growth conditions. There was no difference in polyP levels between wild-type and
      Deltappk strains under all growth conditions tested. In the Deltappk mutant
      proteome, polyP kinase (PPK) was undetectable, but up-regulation of the polyp
      associated proteins polyP adenosine triphosphate (ATP)/nicotinamide adenine
      dinucleotide (NAD) kinase (PpnK), a putative polyP adenosine monophosphate (AMP)
      phosphotransferase (PP_1752), and exopolyphosphatase was observed. Deltappk
      strain exhibited significantly retarded growth with glycerol as carbon and energy
      source (42 h of lag period compared with 24 h in wild-type strain) but similar
      growth to the wild-type strain with glucose. Analysis of gene transcription
      revealed downregulation of glycerol kinase and the glycerol facilitator
      respectively. Glycerol kinase protein expression was also downregulated in the
      Deltappk mutant. The deletion of ppk did not affect motility but reduced biofilm
      formation. Thus, the knockout of the ppk gene has resulted in a number of
      phenotypic changes to the mutant without affecting polyP accumulation.

PMID- 24115626
TI  - The importance of small colonies in sustaining Microcystis population exposed to
      mixing conditions: an exploration through colony size, genotypic composition and
      toxic potential.
AB  - Microcystis is a toxic colony-forming cyanobacterium, which can bloom in a wide
      range of freshwater ecosystems. Despite the ecological advantage of the colonial
      form, few studies have paid attention to the size of Microcystis colonies in the
      field. With the aim of evaluating the impact of a fluctuating physical
      environment on the colony size, the genotypic composition and the toxic potential
      of a Microcystis population, we investigated five different colony size classes
      of a Microcystis bloom in the Grangent reservoir (France). By sequencing the
      internal transcribed spacer of the ribosomal operon, we evidenced changes in the
      genetic structure among size classes in response to environmental change. While
      similar genotypes were seen in every size class in stable conditions, new
      dominant genotypes appeared in the smallest colonies (< 160 MUm) concomitantly
      with mixing conditions, strongly suggesting the importance of these colonies in
      response to disturbances. Moreover, these small colonies played a major role in
      microcystin production during this bloom, since very high microcystin contents (>
      1 pg.cell.(-1)) were found in their cells. These findings indicate that the
      colony size distribution of a Microcystis population in response to disturbance
      could be an adaptive strategy that may explain its ecological success in
      freshwater ecosystems.

PMID- 24115627
TI  - Using stable isotope probing to obtain a targeted metatranscriptome of aerobic
      methanotrophs in lake sediment.
AB  - In this study, we demonstrate the possibility of obtaining a targeted
      metatranscriptome from a functional group of microorganisms using a stable
      isotope probing (SIP) approach. Methanotrophs in lake sediment were labelled
      using (13)CH4, and both labelled and unlabelled-RNA were isolated and sequenced
      by 454 pyrosequencing. The unlabelled metatranscriptome had a large diversity of
      bacterial, archaeal, eukaryotic and viral sequences as expected from a diverse
      sediment community. In contrast, the labelled-RNA metatranscriptome was dominated
      by methanotroph sequences, particularly from Methylococcaceae. Transcripts of the
      methane monooxygenase genes pmoCAB were the most abundant in this
      metatranscriptome, and the pathway of methane oxidation to CO2 could be traced,
      as well as many steps in the ribulose monophosphate pathway for carbon
      assimilation. A high abundance of mRNA transcripts for proteins related to
      motility was detected, suggesting an importance for methanotrophs in lake
      sediments. This combination of SIP and metatranscriptomics should be broadly
      applicable, and will enhance the detection and identification of mRNA from target
      organisms. 

PMID- 24115628
TI  - Strict vegetarian diet improves the risk factors associated with metabolic
      diseases by modulating gut microbiota and reducing intestinal inflammation.
AB  - Low-grade inflammation of the intestine results in metabolic dysfunction, in
      which dysbiosis of the gut microbiota is intimately involved. Dietary fibre
      induces prebiotic effects that may restore imbalances in the gut microbiota;
      however, no clinical trials have been reported in patients with metabolic
      diseases. Here, six obese subjects with type 2 diabetes and/or hypertension were
      assigned to a strict vegetarian diet (SVD) for 1 month, and blood biomarkers of
      glucose and lipid metabolisms, faecal microbiota using 454-pyrosequencing of 16S
      ribosomal RNA genes, faecal lipocalin-2 and short-chain fatty acids were
      monitored. An SVD reduced body weight and the concentrations of triglycerides,
      total cholesterol, low-density lipoprotein cholesterol and haemoglobin A1c, and
      improved fasting glucose and postprandial glucose levels. An SVD reduced the
      Firmicutes-to-Bacteroidetes ratio in the gut microbiota, but did not alter
      enterotypes. An SVD led to a decrease in the pathobionts such as the
      Enterobacteriaceae and an increase in commensal microbes such as Bacteroides
      fragilis and Clostridium species belonging to clusters XIVa and IV, resulting in
      reduced intestinal lipocalin-2 and short-chain fatty acids levels. This study
      underscores the benefits of dietary fibre for improving the risk factors of
      metabolic diseases and shows that increased fibre intake reduces gut inflammation
      by changing the gut microbiota. 

PMID- 24115629
TI  - Hybrid hyaluronic acid hydrogel/poly(E-caprolactone) scaffold provides
      mechanically favorable platform for cartilage tissue engineering studies.
AB  - Hybrid scaffolds for cartilage tissue engineering provide the potential for high
      stiffness properties in tension and compression while exhibiting the viscoelastic
      response found in hydrogels and native cartilage tissue. We investigate the
      impact of a hybrid scaffold fabricated from a hyaluronic acid (HA)-based hydrogel
      combined with porous poly(epsilon-caprolactone) (PCL) material formed by a
      particulate leaching method to study dedifferentiated chondrocyte response. The
      material properties of the hybrid scaffold showed mean Young's moduli in tension
      which were similar to human articular cartilage but not statistically different
      between the hybrid and porous PCL scaffolds at 2.02 and 2.07 MPa, respectively.
      For both the hybrid and porous PCL control scaffolds in compression at low
      loading frequencies (<1 Hz) and 10% strain peak amplitude the Young's moduli are
      not statistically distinct. However, at frequencies in the range of normal human
      gait from 1 to2 Hz, hybrid scaffolds exhibit significantly (p < 0.01) increased
      loss moduli indicating additional contribution of the viscous phase to stiffness.
      Dedifferentiated chondrocytes seeded onto the scaffolds exhibited a rounded
      morphology in hybrid scaffolds however ECM protein expression levels of collagen
      type I, collagen type II, and aggrecan are not different from the PCL control
      scaffolds. These results provide a model platform to investigate cell response to
      mechanical and chemical cues in a hybrid scaffold system with mechanical
      properties similar to human cartilage that does not contribute to differentiation
      in order to identify the appropriate design and development parameters to promote
      formation of extracellular matrix and investigate chondrocyte scaffold
      interactions.

PMID- 24115630
TI  - Is disease recurrence still relevant to graft survival?

PMID- 24115631
TI  - Heterochrony in the regulation of the developing marsupial limb.
AB  - BACKGROUND: At birth, marsupial neonates have precociously developed forelimbs.
      The development of the tammar wallaby (Macropus eugenii) hindlimbs lags
      significantly behind that of the forelimbs. This differs from the grey short
      tailed opossum, Monodelphis domestica, which has relatively similar fore- and
      hindlimbs at birth. This study examines the expression of the key patterning
      genes TBX4, TBX5, PITX1, FGF8, and SHH in developing limb buds in the tammar
      wallaby. RESULTS: All genes examined were highly conserved with orthologues from
      opossum and mouse. TBX4 expression appeared earlier in development than in the
      mouse, but later than in the opossum. SHH expression is restricted to the zone of
      polarising activity, while TBX5 (forelimb) and PITX1 (hindlimb) showed diffuse
      mRNA expression. FGF8 is specifically localised to the apical ectodermal ridge,
      which is more prominent than in the opossum. CONCLUSIONS: The most marked
      divergence in limb size in marsupials occurs in the kangaroos and wallabies. The
      faster development of the fore limb compared to that of the hind limb correlates
      with the early timing of the expression of the key patterning genes in these
      limbs.

PMID- 24115632
TI  - Vitamin B12 deficiency: the great masquerader.
AB  - Vitamin B12 deficiency is rare in children, with nonspecific symptoms including
      failure to thrive, vomiting, anorexia, and neurologic changes with or without
      hematologic disturbances. The neuropathy can be severe and irreversible. We
      report four cases of children with B12 deficiency secondary to adult type
      pernicious anemia, a presumed transport protein abnormality, and a metabolic
      defect. All demonstrated neurologic compromise that improved after initiation of
      B12 therapy. Hematologic manifestations may be preceded by constitutional,
      gastrointestinal, or neurologic changes, and must raise concern for B12
      deficiency. Therapy should be initiated promptly in this setting to prevent
      irreversible neuropathy.

PMID- 24115634
TI  - Direct evidence for the attack of a free N-heterocyclic carbene at a carbonyl
      ligand: a zwitterionic osmium carbonyl cluster.

PMID- 24115633
TI  - SLC26 anion exchangers in uterine epithelial cells and spermatozoa: clues from
      the past and hints to the future.
AB  - The solute carrier 26 (SLC26) family emerges as a distinct class of anion
      transporters with its members SLC26A3 (Slc26a3) and SLC26A6 (Slc26a6) reported to
      be electrogenic Cl(-)/HCO3(-) exchangers. While it is known that uterine fluid
      has high HCO3(-) content and that HCO3(-) is essential for sperm capacitation,
      the molecular mechanisms underlying the transport of HCO3(-) across uterine
      epithelial cells and sperm have not been fully investigated. The present review
      re-examines the results from early reports studying anion transport, finding
      clues for the involvement of Cl(-)/HCO3(-) anion exchangers in electrogenic HCO3(
      ) transport across endometrial epithelium. We also summarise recent work on
      Slc26a3 and Slc26a6 in uterine epithelial cells and sperm, revealing their
      functional role in working closely with the cystic fibrosis transmembrane
      conductance regulator (CFTR) for HCO3(-) transport in these cells. The possible
      involvement of these anion exchangers in other HCO3(-) dependent reproductive
      processes and their implications for infertility are also discussed.

PMID- 24115635
TI  - Biomimetic assembly of the [FeFe] hydrogenase: synthetic mimics in a biological
      shell.
AB  - Combining synthetic chemistry and biology: A new method that allows the
      incorporation of synthetic [FeFe] hydrogenase mimics into the apo-hydrogenase is
      highlighted. Azadithiolato-functionalized model complexes showed similar activity
      to wild-type enzymes when implemented into the protein.

PMID- 24115636
TI  - Chemical synthesis of mono- and bis-labeled pre-microRNAs.

PMID- 24115637
TI  - A biorepository for ophthalmic surgical specimens.
AB  - Biorepositories are collections of surgically obtained human tissues for current
      and future investigations of disease mechanisms, therapeutics, and diagnostics.
      In ophthalmology, a critical challenge is how to interface the operating room
      with the laboratory. To attain standards required for basic research, clinical
      and research teams must cooperate to collect, annotate, and store specimens that
      yield consistent results required for advanced molecular techniques. We developed
      an efficient platform for obtaining vitreous and other eye tissues from the
      operating room and transferring them to the lab. The platform includes a mobile
      lab cart for on-site tissue processing, a multi-user, web-based database for
      point-of-care phenotypic capture, and an integrated data tracking system for long
      term storage. These biorepository instruments have proven essential for our
      studies in ophthalmic disease proteomics. This system can be implemented in other
      operating rooms and laboratories for a variety of biological tissues. 

PMID- 24115638
TI  - Clinical, genetic, and molecular aspects of split-hand/foot malformation: an
      update.
AB  - We here provide an update on the clinical, genetic, and molecular aspects of
      split-hand/foot malformation (SHFM). This rare condition, affecting 1 in 8,500
      25,000 newborns, is extremely complex because of its variability in clinical
      presentation, irregularities in its inheritance pattern, and the heterogeneity of
      molecular genetic alterations that can be found in affected individuals. Both
      syndromal and nonsyndromal forms are reviewed and the major molecular genetic
      alterations thus far reported in association with SHFM are discussed. This
      updated overview should be helpful for clinicians in their efforts to make an
      appropriate clinical and genetic diagnosis, provide an accurate recurrence risk
      assessment, and formulate a management plan.

PMID- 24115639
TI  - Saccharification of biomass using whole solid-state fermentation medium to avoid
      additional separation steps.
AB  - The enzymatic hydrolysis of steam-exploded sugarcane bagasse (SESB) was
      investigated using enzymatic extracts (EE) and whole fermentation media (WM),
      produced in-house, from Aspergillus niger 3T5B8 and Trichoderma reesei Rut-C30
      cultivated on wheat bran under solid-state fermentation (SSF). A detailed and
      quantitative comparison of the different hydrolysis conditions tested was carried
      out using the Chrastil approach for modeling enzymatic reactions by fitting the
      experimental data of total reducing sugar (TRS) released according to hydrolysis
      time. Conversion of SESB using A. niger enzymatic complex were up to 3.2-fold
      higher (in terms of TRS) than T. reesei at similar enzyme loadings, which could
      be correlated to the higher beta-glucosidase levels (up to 35-fold higher) of A.
      niger enzymatic complex. Conversion yields after 72 h exceeded 40% in terms of
      TRS when the WM was supplemented with a low dosage of a commercial enzyme
      preparation. When the combination of WM (from either T. reesei or A. niger) and
      commercial cellulase was used, the dosage of the commercial enzyme could be
      reduced by half, while still providing a hydrolysis that was up to 36% more
      efficient. Furthermore, SESB hydrolysis using either EE or WM resulted in similar
      yields, indicating that the enzyme extraction/filtration steps could be
      eliminated from the overall process. This procedure is highly advantageous in
      terms of reduced enzyme and process costs, and also avoids the generation of
      unnecessary effluent streams. Thus, the enzymatic conversion of SESB using the WM
      from SSF is cost-effective and compatible with the biorefinery concept.

PMID- 24115640
TI  - Magnolol-induced inhibition of tumor growth in systemic malignancies.
AB  - The commentary illustrates the significant tumor attenuating effects of magnolol
      and refers to the article on "Screening active anti-breast cancer compounds from
      Cortex Magnolia officinalis by 2D LC-MS" (X. Hou, et al., J. Sep. Sci. 2013, 36
      (4), 706-712). On the basis of the literature, there is definitively need for
      further studies to fully understand the magnolol reation pathways and to harness
      the antineoplastic effects.

PMID- 24115641
TI  - Staphylococcus aureus nasal isolates from healthy individuals cause highly
      variable host cell responses in vitro: the Tromso Staph and Skin Study.
AB  - Studies on Staphylococcus aureus populations colonizing the nasal cavity reveal
      that some bacterial strains are more common, while others are rarely found. This
      study included five isolates with the most common spa types and five isolates
      with rare spa types from healthy population. Selected phenotypic traits and
      genomic content among nasal S. aureus isolates were compared. Besides the rather
      similar growth rates, our data revealed a high diversity among isolates; that is,
      in biofilm formation, the ability to attach to and be internalized in
      keratinocytes as well as ability to induce pro- and anti-inflammatory cytokines.
      The results showed that S. aureus isolates from healthy hosts are phenotypically
      diverse and cause highly variable host cell responses. Therefore, generalizing
      the results from one S. aureus isolate to all is highly questionable. 

PMID- 24115642
TI  - Selective C-F bond activation: substitution of unactivated alkyl fluorides using
      YbI3.

PMID- 24115643
TI  - Origin of tunable photocatalytic selectivity of well-defined alpha-Fe(2)O(3)
      nanocrystals.
AB  - Visible-light induced degradation of an aqueous mixture containing MO and RhB on
      well-defined alpha-Fe2 O3 nanocrystals shows that MO degradation is more
      favorable and such selectivity on the {012} facet is greater than that on {001}.
      The origin of selectivity is rationalized as the inherent surface structural
      difference and preferential molecular adsorption. 

PMID- 24115644
TI  - Therapeutic vaccination of a liver transplant recipient suffering from fulminant
      hepatitis B during pregnancy.

PMID- 24115645
TI  - Treatment of multiply relapsed wilms tumor with vincristine, irinotecan,
      temozolomide and bevacizumab.
AB  - As most active chemotherapy agents against Wilms tumor are incorporated into
      upfront therapy, particularly for those patients with high risk for recurrence,
      novel regimens are needed to treat children with relapsed Wilms tumor. We
      describe four consecutive patients with multiply relapsed Wilms tumor who were
      treated with a combination of vincristine, irinotecan, temozolomide, and
      bevacizumab. Two had a complete response, and two had a partial response to
      treatment. Hematological toxicity and diarrhea were the main side effects. This
      regimen has activity in patients with multiply relapsed Wilms tumor without
      excessive toxicity, and should be evaluated further in this setting.

PMID- 24115646
TI  - Palladium-catalyzed direct synthesis of phosphole derivatives from
      triarylphosphines through cleavage of carbon-hydrogen and carbon-phosphorus
      bonds.

PMID- 24115647
TI  - Fibronectin promotes migration and invasion of ovarian cancer cells through up
      regulation of FAK-PI3K/Akt pathway.
AB  - Ovarian cancer is the leading cause of death from gynecological malignancy, and
      the fourth most common cause of cancer death among American women. This study
      investigates the mechanism of fibronectin (FN) in stimulating ovarian cancer cell
      migration and invasion through up-regulation of focal adhesion kinase (FAK)
      pathway. Human ovarian cancer cells (OVCAR-3, A2780/CP70) were cultured and
      treated with fibronectin (10 ug/mL). Trans-well plates were used to conduct the
      migration assay, real-time RT-PCR for FAK mRNA expression, and FAK siRNA for
      blocking FAK expression. Western blots were used for P-FAK, P-PI3K, and P-Akt
      analysis. Fibronectin-treated OVCAR-3, A2780/CP70 cells have increased ability to
      migrate and invade. It significantly promoted this behavior through the
      phosphorylation of FAK. The cell displayed significantly increased signaling
      regulation of the FAK pathway (p-PI3K/P-Akt). Furthermore, siRNA FAK-treated
      cells had reduced the levels of p-PI3K/P-Akt after induced by fibronectin. Our
      results indicate that FAK inhibition can suppress ovarian cancer cells migration
      and invasion through inhibiting downstream signaling (PI3K/AKT), which might be a
      therapeutic target or biomarker for ovarian cancer. 

PMID- 24115649
TI  - Enantioselective sulfonation of enones with sulfonyl imines by cooperative N
      heterocyclic-carbene/thiourea/tertiary-amine multicatalysis.
AB  - Many hands make light work: In an organocatalytic asymmetric sulfonation of
      enones, the activation of a sulfonyl imine by an N-heterocyclic carbene (NHC)
      catalyst led to the release of a sulfinic anion, which underwent nucleophilic
      addition to the enone. The enantioselectivity of the process was controlled by a
      chiral thiourea/amine co-catalyst through anion recognition and hydrogen-bonding
      interactions. Tol=p-tolyl. 

PMID- 24115650
TI  - New biologically active hydrogen sulfide donors.
AB  - Generous donors: The dithioperoxyanhydrides (CH3 COS)2 , (PhCOS)2 , CH3 COSSCO2
      Me and PhCOSSCO2 Me act as thiol-activated hydrogen sulfide donors in aqueous
      buffer solution. The most efficient donor (CH3 COS)2 can induce a biological
      response in cells, and advantageously replace hydrogen sulfide in ex vivo
      vascular studies. 

PMID- 24115648
TI  - Patterning of sexually dimorphic neurogenesis in the caenorhabditis elegans
      ventral cord by Hox and TALE homeodomain transcription factors.
AB  - BACKGROUND: Reproduction in animals requires development of distinct neurons in
      each sex. In C. elegans, most ventral cord neurons (VCNs) are present in both
      sexes, with the exception of six hermaphrodite-specific neurons (VCs) and nine
      pairs of male-specific neurons (CAs and CPs) that arise from analogous precursor
      cells. How are the activities of sexual regulators and mediators of neuronal
      survival, division, and fate coordinated to generate sex-specificity in VCNs?
      RESULTS: To address this, we have developed a toolkit of VCN markers that allows
      us to examine sex-specific neurogenesis, asymmetric fates of daughters of a
      neuroblast division, and regional specification on the anteroposterior axis.
      Here, we describe the roles of the Hox transcription factors LIN-39 and MAB-5 in
      promoting survival, differentiation, and regionalization of VCNs. We also find
      that the TALE class homeodomain proteins CEH-20 and UNC-62 contribute to
      specification of neurotransmitter fate in males. Furthermore, we identify that
      VCN sex is determined during the L1 larval stage. CONCLUSIONS: These findings,
      combined with future analyses made possible by the suite of VCN markers described
      here, will elucidate how Hox-mediated cell fate decisions and sex determination
      intersect to influence development of neuronal sex differences.

PMID- 24115651
TI  - Fragile X syndrome: From protein function to therapy.
AB  - Fragile X syndrome (FXS) is the leading monogenic cause of intellectual
      disability and autism. The FMR1 gene contains a CGG repeat present in the 5'
      untranslated region which can be unstable upon transmission to the next
      generation. The repeat is up to 55 CGGs long in the normal population. In
      patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs
      generally leads to methylation of the repeat and the promoter region, which is
      accompanied by silencing of the FMR1 gene. The disease is a result of lack of
      expression of the fragile X mental retardation protein leading to severe
      symptoms, including intellectual disability, hyperactivity, and autistic-like
      behavior. The FMR1 protein (FMRP) has a number of functions. The translational
      dysregulation of a subset of mRNAs targeted by FMRP is probably the major
      contribution to FXS. FMRP is also involved in mRNA transport to synapses where
      protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator
      of mRNA stability either by sustaining or preventing mRNA decay. Increased
      knowledge about the role of FMRP has led to the identification of potential
      treatments for fragile X syndrome that were often tested first in the different
      animal models. This review gives an overview about the present knowledge of the
      function of FMRP and the therapeutic strategies in mouse and man.

PMID- 24115653
TI  - [Phylogeographic analyses of Sarcocheilichthys nigripinnis(Teleostei:
      Cyprinidae)based on mitochondrial DNA Cyt b gene sequences].
AB  - Sarcocheilichthys nigripinnis is a small cyprinid fish widely distributed in East
      Asia, and it has been widely used in biogeographic analyses of freshwater fishes
      in China. In the present study, 142 S. nigripinnis individuals from 20 sampling
      sites in eight river systems were collected to investigate its phylogeography and
      genetic variations.. Populations from the Yellow River represent northern clade
      and all others represent southern clade. The results showed that 56 haplotypes
      were identified as mitochondrial DNA (mtDNA) Cyt b gene of 1 140 bp length.
      Relatively high haplotype diversity (h=0.971) and low nucleotide diversity
      (pi=0.0212) were detected, and the estimated average genetic distance was 2.2%.
      Moreover, a neighbor-joining(NJ)tree revealed seven strongly supported lineages.
      Populations from the Yellow River were located at the basal position, whereas the
      remaining populations were more derived. Our results indicate that S. czerskii
      might have been evolved from S. nigripinnis in the Yellow River ~1.03 Ma. Based
      on the phylogeographical analysis of S. nigripinnis, we also suggest that
      vicariance, following mountain uplift and drainage isolation, plays an important
      role in producing evolutionary lineage differentiations. Moreover, molecular
      dating estimated that the divergence time of S. czerskii could be dated back to
      0.95~3.92 Ma. Mismatch distribution analysis and neutrality tests also suggested
      the recent demographic expansions of S. nigripinnis populations, and that the
      effects of Pleistocene climatic changes could be a vital factor of the population
      dynamics of S. nigripinnis. 

PMID- 24115652
TI  - Translational vitreous proteomics.
AB  - The vitreous is an extracellular matrix that is still poorly understood. Although
      many constituents and characteristics have been previously determined, there are
      many attributes still being discovered. Currently, using protein arrays, MS, and
      bioinformatics, the vitreous provides a wealth of knowledge regarding ocular
      diseases and potential targets for personalized therapeutics. 

PMID- 24115654
TI  - [Establishment of full-sib families of Branchiostoma japonicum and the
      relationship between early development patterns and larvae survival rates].
AB  - One general requirement of individual laboratory animals is that they have known
      genetic backgrounds. However, ensuring such genetic similarity is difficult, and
      can be facilitated by breeding a full strain for experimentation. To this end,
      the authors bred 34 full-sib families of amphioxus larvae/embryos. Due to the
      high mortality of the embryos and larvae, only seven full-sib families of
      juvenile amphioxus Branchiostoma japonicum were obtained. Among them, the highest
      and lowest survival ratios were 32.4% and 1.67%, respectively, whereas the
      shortest metamorphosis and longest larva duration were 24 d and 42 d,
      respectively. These results demonstrate the feasibility of establishing full-sib
      families of amphioxus, and provide fundamental data needed for the future
      breeding of amphioxus strains. 

PMID- 24115655
TI  - [Population trends and behavioral observations of wintering common cranes (Grus
      grus) in Yancheng Nature Reserve].
AB  - To understand the population status and behavioural features of wintering common
      cranes in the Yancheng Nature Reserve, two transects were established and
      population trends were monitored every month over five recent winters from 2008
      to 2013. Wintering behaviours were also observed in order to explore the possible
      effects of family size and age on time budgets. Results indicated that the
      populations were stable with a range of 303 to 707 individuals. Negative effects
      of coastal developments were not found on the wintering population of common
      cranes, which might be related to their diets and preference for artificial
      wetland habitats. We found a significant effect of age on time budgets, with
      juveniles spending more time feeding and less time alerting, which might be
      related to the needs of body development and skill learning. Family size did not
      affect the time budgets of the cranes, which indicated that adults did not
      increase vigilance investment even when raising a larger family. 

PMID- 24115656
TI  - [A new blind barbine species, Sinocyclocheilus anshuiensis sp.
      nov.(Cypriniformes: Cyprinidae)from Guangxi, China].
AB  - This study describes a new blind barbine fish species, Sinocyclocheilus
      anshuiensis sp. nov. discovered based on five specimens collected from a cave in
      Luolou town, Lingyun County, Guangxi, China, in June and July 2012.
      Sinocyclocheilus anshuiensis is distinguished from other species of
      Sinocyclocheilus by having the following combination of characteristics: dorsal
      fin with 7 branched rays, last unbranched dorsal-fin ray weak with serrations on
      posterior edge of its lower part; pelvic-fin origin anterior to dorsal-fin
      origin; dorsal profile of head sharply uplift, a forward flesh tuber present on
      frontal; body covered with scales, and lateral line with 34-38 scales, lateral
      line scales are as big as their neighbor scales; caudal peduncle with developed
      fresh crests. 

PMID- 24115657
TI  - [Histological observations of Medaka(Oryzias latipes)gonad sexual differentiation
      and development].
AB  - Over the past few decades, Medaka (Oryzias latipes) has become a model animal in
      teleost species research due both to its short reproductive cycle and efficient
      proliferate capacity. Unfortunately, however, systematic data of its sexual
      differentiation and development have yet to be obtained. In the present study, we
      observed Medaka gonad development from the earliest recognizable stages through
      differentiation to maturation under a light microscope, after paraffin sectioning
      and hematoxylin-eosin staining. The results showed that among juveniles aged 5 to
      10 days, the gonad located on the right side of the dorsal abdominal cavity and
      the germ cells was significantly larger than the surrounding somatic cells. Ten
      days after hatching, sexual differences between females and males became obvious,
      and germline cysts derived from oogonium division were present in the gonad. At
      50 days after hatching, ovarian cavities and mature sperm were observed.
      Moreover, during the study we also observed the coexistence of two sexual
      characteristics during a male's development. Together, these observations fill
      current gaps in developmental and genetic biology that will allow a more
      efficient use of Medaka as an experimental model. 

PMID- 24115658
TI  - [Morphological differentiation of Garra orientalis(Cyprinidae)among different
      geographical populations].
AB  - Morphological differences were found among specimens of Garra orientalis from
      Minjiang River, Pearl River, Red River and Hainan Island. To confirm whether the
      morphological differences among these geographical populations had reached the
      level of subspecies or species, seventy-two specimens of Garra orientalis were
      divided into four groups according to the four drainage areas stated above. Ten
      external morphological characteristics were observed. Thirteen frame
      characteristics and twenty-three general characteristics were measured and
      analyzed for multivariate morphometrics. In scatter plots of principal
      components, the specimens from Hainan Island were relatively concentrated on the
      scatter plots, but were not completely separated from the other three drainages.
      The samples from the other three drainages were completely mixed together. These
      results indicated that the specimens from the different drainages could not be
      distinguished by morphological comparison and morphometric analysis. Species or
      subspecies level differentiation of Garra orientalis among geographical
      populations could instead be studied by molecular biological methods in the
      future. 

PMID- 24115659
TI  - [Spectra analysis reveals the sexual dichromatism of red-eared slider
      turtle(Trachemys scripta)].
AB  - In this study,spectra analysis was conducted to investigate the sexual
      dichromatism and relationship between body color and quality of the red-eared
      slider turtle (Trachemys scripta). Visual modeling revealed that the differences
      of the hues of body colors' ultraviolet (UV) components between male and female
      were significant. Moreover, the visible(VIS)components of the hues of forelimbs
      were correlated with body qualities of male but not of female. Our results
      indicated that UV might act as a signal for sexual cognition in red-eared slider
      turtles, and female might evaluate male by the VIS components of the hues of
      forelimbs. These findings provided preliminary results and perspectives to the
      sexual dichromatism and sexual selection behaviors of red-eared slider turtles. 

PMID- 24115660
TI  - [Cytogenetic and molecular genetic analysis of gynogenesis in Megalobrama
      amblycephala using spermatozoa of Erythroculter ilishaeformis].
AB  - In the present study we used both cytogenetics (measurement of DNA content,
      detection of chromosome number, observation of gonadal development)and molecular
      genetics(microsatellite analysis)to analyze the biological characteristics of
      gynogenetic M. amblycephala, which werecreatedthrough gynogenesis induced via UV
      irradiated E. ilishaeformis spermatozoa to fertilize M. amblycephala eggs. The
      maternal genome was duplicated by cold shock in 0~4C cold water to form a
      population of M. amblycephala with 48 chromosomes whose DNA content was identical
      to the diploid maternal parent. Morphologically, this group of gynogenetic M.
      amblycephala was similar to the control group. All gynogenetic M. amblycephala
      were female, and no males were found in any of the examined gynogenetic M.
      amblycephala, providing cytogenetic evidence that our gynogenetic M. amblycephala
      are type XY. At the same time, microsatellite analysis showed that 63 alleles
      were amplified in the three test groups of gynogenetic M. amblycephala. Overall,
      the population of gynogenetic M. amblycephala observed heterozygosity average,
      and the expected average was significantly lower than the parental averages,
      demonstrating that after generation gynogenesis the gene homozygosity of M.
      amblycephala was significantly higher than the ordinary bream and E.
      ilishaeformis, making it a pure line. The genetic proximity of gynogenetic M.
      amblycephala to M. amblycephala demonstrates that gynogenesis passes on maternal
      DNA. Gynogenetic groups developed in this study may provide good genetic material
      for future breeding projects of M. amblycephala. 

PMID- 24115661
TI  - [Perinatal clomiphene citrate treatment changes sexual orientations of male
      mice].
AB  - Perinatal period and adolescence are critical for brain development, which is the
      biological basis of an individual's sexual orientation and sexual behavior. In
      this study, animals were divided into two groups and their sexual orientations
      were observed: one group experienced drug treatments during the perinatal period,
      and the other group was castrated at puberty. The results showed that estradiol
      treatment had no effect on mature male offspring's sexual orientations, but 9
      days and 14 days of clomiphene citrate treatment significantly increased the
      chance of homosexuality and effeminized behavior. In addition, the sexual
      orientation of mature normal male offspring, which were castrated when they were
      21 days old,was not significant different from the control animals. These
      findings suggest that the inhibition of perinatal estrogen activities could
      suppress individual male-typical responses, enhance female-typical responses and
      induce homosexual orientations. Moreover, the masculinizing effects of estrogen
      were more obvious during perinatal period than adolescence. 

PMID- 24115662
TI  - [Diet composition and transition of clearhead icefish(Protosalanx hyalocranius)in
      Lake Xingkai].
AB  - Diet compositions of alien clearhead icefish(Protosalanx hyalocranius)in Lake
      Xingkai were investigated monthly from June 2010 through January 2011.
      Protosalanx hyalocranius preyed mainly on cladoceran, copepoda, shrimp, and
      larvae or juvenile fish. In June, P. Hyalocranius were smaller than 60 mm
      standard length(SL), and their diets were composed of zooplankton only. In July,
      fish began to appear infrequently in the diet of P. Hyalocranius larger than 60
      mm SL, and by August fish was occurring in the diets of P. hyalocranius larger
      than 80 mm, 100 mm in September, and 120 mm in October and thereafter,
      respectively. The increase in the minimum SL of P. hyalocranius preying on fish
      within a given season reflects changes in resource availability, largely
      attributed to the corresponding increase in prey fish size as seasons progress.
      Protosalanx hyalocranius and Hemiculter sp. were the dominant prey fish in the
      diets of P. hyalocranius. 

PMID- 24115663
TI  - [Use of alizarin red S and alizarin complexone for immersion marking
      Sinocyclocheilus grahami].
AB  - In the present study, we examined the potential uses of Alizarin complexone and
      Alizarin red S to mark S. grahami larvae and juveniles. Individuals of different
      ages (6 days, 20 days, 90 days) were immersed in four concentrations of a
      solution of each chemical (50, 100, 150 and 200 mg/L) for different periods of
      time (4-36 h). Marked individuals were euthanized 4-27 days after immersion, and
      the lapillus was removed and used to determine mark quality. After marking with
      50-150 mg/L ALC and ARS, violet marks were visible under normal light, and
      scarlet fluorescent marks were visible under 510-560 nm green light. The clear
      marks under normal light were recorded, and a 100% survival rate was guaranteed
      under the following conditions: 6 day old larvae immersed in 50 mg/L ALC or ARS
      for 8h; 20 day old larvae immersed in 50 mg/L ALC or 100 mg/L ARS for 24h; 90 day
      old juveniles immersed in 100mg/L ALC or 150 mg/L ARS for 24 h. 

PMID- 24115664
TI  - [Two new Cypriniformes fish records from Yunnan Province-Carassioides acuminatus
      and Hemimyzon pumilicorpora].
AB  - Two new Cypriniformes fish records from Yunnan Province, Carassioides acuminatus
      (collected from mainstream of Red River in Hekou County) and Hemimyzon
      pumilicorpora (collected from Gula River, Gula Town, Funing County, upper stream
      of the Pearl River drainage), were identified during fish specimen sorting at
      Kunming Institute of Zoology, Chinese Academy of Sciences. These two new records
      not only clarify the distribution patterns of the two species, but also enrich
      the knowledge of native fishes of Yunnan Province. 

PMID- 24115665
TI  - [Eurasian Blackcap (Sylvia atricapilla)-a new bird record in China].
AB  - A new bird species record, the Eurasian Blackcap (Sylvia atricapilla), was
      witnessed and subsequently recorded from 22 December 2012 to 9 January 2013, in
      Kashi (N39 degrees 28', E76 degrees 00', altitude 1 260 m), southwest Xinjiang,
      China. 

PMID- 24115666
TI  - [Transcription activator-like effectors(TALEs)based genome engineering].
AB  - Systematic reverse-engineering of functional genome architecture requires precise
      modifications of gene sequences and transcription levels. The development and
      application of transcription activator-like effectors(TALEs) has created a wealth
      of genome engineering possibilities. TALEs are a class of naturally occurring DNA
      binding proteins found in the plant pathogen Xanthomonas species. The DNA-binding
      domain of each TALE typically consists of tandem 34-amino acid repeat modules
      rearranged according to a simple cipher to target new DNA sequences. Customized
      TALEs can be used for a wide variety of genome engineering applications,
      including transcriptional modulation and genome editing. Such "genome
      engineering" has now been established in human cells and a number of model
      organisms, thus opening the door to better understanding gene function in model
      organisms, improving traits in crop plants and treating human genetic disorders. 

PMID- 24115667
TI  - [Advances in the study of neuroendocrinological regulation of kisspeptin in fish
      reproduction].
AB  - Kisspeptin, a key factor in the neuroendocrinological regulation of animal
      reproduction, is a peptide product encoded by kiss genes, which act as the
      natural ligand of GPR54. Over the last decade, multiple functional molecular
      forms of kisspeptin have been found in vertebrate species. In fish, the major
      molecular structural form is kisspeptin-10. The kisspeptin/GPR54 system has
      multiple important functions in reproduction. This review provides an overview of
      our current knowledge on kisspeptin and its role in regulating fish reproductive,
      including the distribution and location of kisspeptin neurons in the brain, the
      molecular polymorphism of fish kisspeptin, functional diversity, the molecular
      mechanism of fish reproductive regulation, and the molecular evolution of
      kisspeptin as well as the co-regulation of fish reproduction by kisspeptin and
      other functional molecules. Perspectives on the future of kisspeptin regulation
      in fish reproduction are also highlighted. 

PMID- 24115668
TI  - The first mitochondrial genome for the butterfly family Riodinidae (Abisara
      fylloides) and its systematic implications.
AB  - The Riodinidae is one of the lepidopteran butterfly families. This study
      describes the complete mitochondrial genome of the butterfly species Abisara
      fylloides, the first mitochondrial genome of the Riodinidae family. The results
      show that the entire mitochondrial genome of A. fylloides is 15 301 bp in length,
      and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA
      genes and a 423 bp A+T-rich region. The gene content, orientation and order are
      identical to the majority of other lepidopteran insects. Phylogenetic
      reconstruction was conducted using the concatenated 13 protein-coding gene (PCG)
      sequences of 19 available butterfly species covering all the five butterfly
      families (Papilionidae, Nymphalidae, Peridae, Lycaenidae and Riodinidae). Both
      maximum likelihood and Bayesian inference analyses highly supported the monophyly
      of Lycaenidae+Riodinidae, which was standing as the sister of Nymphalidae. In
      addition, we propose that the riodinids be categorized into the family Lycaenidae
      as a subfamilial taxon. 

PMID- 24115669
TI  - Differentiation in cranial variables among six species of Hylopetes (Sciurinae :
      Pteromyini).
AB  - There is some discrepancy in the classification of different species of
      Hylopetes, particularly regarding systematic status of H. electilis and H.
      phayrei and their relationship to other species. In the present study, for the
      first time we have brought together six of the nine Hylopetes species and
      performed statistical analysis of 14 measurable cranial variables, analyzing in
      total 89 specimens, including H. electilis, H. alboniger, H. phayrei, H. lepidus,
      H. spadiceus, and H. nigripes. Both univariate and multivariate analysis results
      indicate that H. electilis can not only be obviously distinguished from H.
      phayrei, but also clearly differs from the other four Hylopetes species. These
      results sustain the contention that H. electilis is neither a synonym nor
      subspecies of H. phayrei,but should be considered a distinct and valid species.
      Subsequently, a straightforward discussion on the biogeography of Hylopetes in
      southeastern Asia gives further insight into the differentiation and variety of
      species belonging to this genus.

PMID- 24115670
TI  - Three-dimensional morphology of the Sinocyclocheilus hyalinus (Cypriniformes :
      Cyprinidae) horn based on synchrotron X-ray microtomography.
AB  - Sinocyclocheilus is a cave-dwelling cyprinid genus endemic to southwest China.
      Several species possess a conspicuous horn on their head, which has been
      suggested as a constructive troglomorphic trait but lacks substantial evidence.
      We used non-invasive, high spatial resolution synchrotron X-ray microtomography
      to investigate the three-dimensional (3D) morphology of the horn of
      Sinocyclocheilus hyalinus, one of eight such troglobiotic species. 3D renderings
      demonstrated the osteological components, which were comprised of a rear wall
      comprised of the supraoccipital bone, a remaining frontal wall with numerous
      fenestrae, and the bottom continuous with the parietal and epiotic. A horn cavity
      occurred within the horn. The fenestrae in the frontal wall were continuous in
      the horn cavity and showed elaborate channeling, and were, connected to the
      cranial cavity by soft tissue. We tentatively called this configuration the
      "otocornual connection" due to its anatomic and putative functional similarity to
      the otolateralic connection in clupeids and loricariids, which provide an
      indirect pathway to enhance perception of underwater sound signals. This study
      provides a functional morphology context for further histological and
      physiological investigations of such horn structures in Sinocyclocheilus
      cavefish, and we suggest that the horn might enhance acoustic perception to
      compensate for visual loss in subterranean life, which warrants future
      physiological examination as lab-reared S. hyalinus become available. 

PMID- 24115671
TI  - Effects of Zn2+ and Cu2+ on loach ovaries and ova development.
AB  - This study compared the accumulation of Zn2+ and Cu2+ in the ovaries and ova of
      loaches under different concentrations of Zn2+ (1.00, 2.50 and 5.00 mg/L
      respectively) and Cu2+ (0.10, 0.25 and 0.50 mg/L respectively). The results
      showed that both Zn2+ and Cu2+ accumulated in the ovaries, and that the
      relationship between accumulation and time was linear over 20 days of exposure.
      The accumulation of the metals in ovaries was closely related to the
      concentration of exposure in the solutions (P<0.05), and was obviously affected
      by the time and doses. However, the Cu2+ concentration was significantly higher
      than Zn2+ (P<0.05). The development level of ova in the ovaries also correlated
      with the concentration and exposure period in the Zn2+ and Cu2+ solutions.

PMID- 24115672
TI  - Description of a new Pratylenchus species from China (Tylenchida,
      Pratylenchidae).
AB  - Pratylenchus ekrami from maize (Zea mays) roots in Shenyang and luffa (Luffa
      cylindrica) roots in Dalian, China, are described in this paper. Nematodes from
      the two areas were identified consistently, and were characterized by a heavy
      cephalic sclerotization, extending posteriorly up to two body annuli, stylet 11
      13 MUm long, elongating conoid tail, and becoming thinner from vulva. Males were
      not found. Pratylenchus ekrami is close to Pratylenchus vulnus, but the most
      critical characteristics between the two species were the number of lip annuli,
      stylet size, and shape of stylet knobs. This species is the first reported in
      China. 

PMID- 24115673
TI  - Identification and characterization of a novel inhibitor of alginate
      overproduction in Pseudomonas aeruginosa.
AB  - In this study, we performed whole-genome complementation using a PAO1-derived
      cosmid library, coupled with in vitro transposon mutagenesis, to identify gene
      locus PA1494 as a novel inhibitor of alginate overproduction in P. aeruginosa
      strains possessing a wild-type mucA. 

PMID- 24115674
TI  - Retrograde aortic valve crossing of the CoreValve prosthesis using the buddy
      balloon technique.
AB  - In rare cases, retrograde aortic valve crossing during transcatheter aortic valve
      implantation may be challenging despite improvements in delivery catheter
      profile, size, and steerability compared with the first generation devices.
      Herein, we report a case of challenging transfemoral Medtronic CoreValve
      placement that was possible, thanks to the buddy balloon technique, using a
      peripheral 6-F compatible balloon.

PMID- 24115676
TI  - Iron-catalyzed oxidative C-H/C-H cross-coupling: an efficient route to alpha
      quaternary alpha-amino acid derivatives.
AB  - Fully loaded: A coordinating activation strategy has been developed to furnish
      alpha-quaternary alpha-amino acids through the iron(III)-catalyzed oxidative
      functionalization of alpha-C(sp(3) )?H bonds of alpha-tertiary alpha-amino acid
      esters. The reaction exhibits a broad substrate scope for both alpha-amino acids
      and nucleophiles (Nu) as well as good functional-group tolerance (see scheme,
      DTBP=di-tert-butyl peroxide, DCE=1,2-dichloroethane). 

PMID- 24115675
TI  - In vivo immune cell distribution of gold nanoparticles in naive and tumor bearing
      mice.
AB  - Gold nanoparticles (AuNP) have been widely used for drug delivery and have
      recently been explored for applications in cancer immunotherapy. Although AuNPs
      are known to accumulate heavily in the spleen, the particle distribution within
      immune cells has not been thoroughly studied. Here, cellular distribution of Cy5
      labeled 50 nm AuNPs is characterized within the immune populations of the spleen
      from naive and tumor bearing mice using flow cytometry. Surprisingly,
      approximately 30% of the detected AuNPs are taken up by B cells at 24 h, with
      about 10% in granulocytes, 18% in dendritic cells, and 8% in T cells. In
      addition, 3% of the particles are detected within myeloid derived suppressor
      cells, an immune suppressive population that could be targeted for cancer
      immunotherapy. Furthermore, it is observed that, over time, the particles
      traveled from the red pulp and marginal zone to the follicles of the spleen.
      Taking into consideration that the particle cellular distribution does not change
      at 1, 6 and 24 h, it is highly suggestive that the immune populations carry the
      particles and migrate through the spleen instead of the particles migrating
      through the tissue by cell-cell transfer. Finally, no difference is observed in
      particle distribution between naive and tumor bearing mice in the spleen, and
      nanoparticles are detected within 0.7% of dendritic cells of the tumor
      microenvironment. Overall, these results can help inform and influence future
      AuNP delivery design criteria including future applications for nanoparticle
      mediated immunotherapy. 

PMID- 24115677
TI  - Structural and physicochemical aspects of silica encapsulated ZnO quantum dots
      with high quantum yield and their natural uptake in HeLa cells.
AB  - Photoluminescent semiconductor quantum dots (QDs) are of significant interest for
      bioimaging and fluorescence labeling. In this regard, we describe here the design
      of high sensitivity and high specificity non-toxic ZnO QDs (~5 nm) with long-term
      stability of up to 12 months. The embedding of ZnO QDs on silica nanospheres led
      to significant increase in photoluminescence intensity rendering them highly
      bright QD-based probes. The QDs were characterized in vitro with respect to
      cancer cells (HeLa) and evaluated in terms of viability, fluorescence and
      cytoskeletal organization. The immobilization of ZnO QDs on silica nanospheres
      promoted the internalization and enhanced fluorescence emission of HeLa cells.
      The fluorescence emission from QDs was stable for 3 days, indicating excellent
      stability toward photobleaching. Cytoskeletal reorganization was observed after
      internalization of QDs such that the ZnO QDS on silica nanospheres resulted in
      broadening of the actin cytoskeleton. The study underscores that ZnO QDs
      immobilized on Si nanospheres are promising for tracking cancer cells in cell
      therapy.

PMID- 24115678
TI  - Rituximab as therapy for the recurrence of bile salt export pump deficiency after
      liver transplantation.
AB  - Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from
      recessive mutations in the adenosine triphosphate-binding cassette B11 gene,
      which encodes for bile salt export pump (BSEP). Liver transplantation (LT) is
      offered to PFIC2 patients with end-stage liver disease. Reports have described
      recurrent cholestasis in PFIC2 patients after transplantation, and this has been
      associated with immunoglobulin G antibodies to BSEP. High-titer anti-BSEP
      antibodies appear to correlate with episodes of cholestatic graft dysfunction.
      There is no established paradigm for treating antibody-mediated posttransplant
      BSEP disease. It appears to be refractory to changes in immunosuppressant
      medications that would typically be effective in treating allograft rejection.
      Taking what is known about its pathophysiology, we designed a treatment
      consisting of rituximab, a chimeric monoclonal anti-CD20 antibody, in combination
      with intravenous immunoglobulin and plasmapheresis. Using this approach, we
      report the successful management of 2 patients with antibody-mediated recurrence
      of PFIC2 after LT.

PMID- 24115679
TI  - Bioinspired, cytocompatible mineralization of silica-titania composites:
      thermoprotective nanoshell formation for individual chlorella cells.
AB  - Hard-shell case: Using a (RKK)4 D8 peptide allows mineralization to occur under
      cytocompatible conditions. Thus individual Chlorella cells could be encapsulated
      within a SiO2 -TiO2 nanoshell with high cell viability (87 %). The encapsulated
      Chlorella showed an almost threefold increase in their thermo-tolerance after 2 h
      at 45  degrees C. 

PMID- 24115680
TI  - Metabolic engineering of Escherichia coli for the production of phenol from
      glucose.
AB  - Phenol is an industrially versatile commodity chemical and is currently produced
      from fossil resources. Phenol's biological production from renewable resources
      has been limited due to its toxicity to microorganisms. Here, we simultaneously
      engineered 18 Escherichia coli strains for the production of phenol using
      synthetic regulatory small RNA (sRNA) technology. sRNA-based knock-down of the
      two regulators and overexpression of the genes involved in the tyrosine
      biosynthetic pathway together with tyrosine phenol-lyase (TPL) in E. coli strains
      resulted in the production of phenol from glucose. The 18 engineered E. coli
      strains showed significant differences in the production of tyrosine (i.e. the
      immediate precursor for phenol), TPL activity, and tolerance to phenol. Among the
      engineered E. coli strains, the BL21 strain produced phenol most efficiently: 419
      mg/L by flask culture and 1.69 g/L by fed-batch culture. The final titer and
      productivity were further improved through biphasic fed-batch fermentation using
      glycerol tributyrate as an extractant of phenol. The concentration of phenol in
      the glycerol tributyrate phase and fermentation broth reached 9.84 and 0.3 g/L,
      respectively, in 21 hours, which translates into the final phenol titer and
      productivity of 3.79 g/L and 0.18 g/L/h, respectively. This is the highest titer
      achieved by microbial fermentation. Although further engineering is required to
      be competitive with the current petro-based process, the strategies used for the
      development of the engineered strain and fermentation process will provide a
      valuable framework for the microbial production of toxic chemicals. 

PMID- 24115681
TI  - Therapeutic effects of hepatocyte growth factor-overexpressing human umbilical
      cord blood-derived mesenchymal stem cells on liver fibrosis in rats.
AB  - Fibrosis is a common end stage for a variety of liver diseases, including most
      chronic liver diseases, and results from an imbalance between collagen deposition
      and degradation. Mesenchymal stem cells (MSCs) have the ability to migrate into
      fibrotic livers and differentiate into hepatocytes. Hepatocyte growth factor
      (HGF) has potent anti-apoptotic and mitogenic effects on hepatocytes during liver
      injury and plays an essential role in the development and regeneration of the
      liver. In this study, human HGF-overexpressing human umbilical cord blood-derived
      MSCs (hHGF-HUCB-MSCs) were prepared using the pMEX Expression System, and the
      upregulation of hHGF expression was confirmed by RT-PCR and ELISA. HGF expressed
      by hHGF-HUCB-MSCs exerted a stimulatory effect on hepatocyte proliferation in
      vitro. hHGF-HUCB-MSCs were transplanted to investigate the therapeutic effects of
      these cells on carbon tetrachloride (CCL4)-induced liver fibrosis in a rat model.
      After 4 weeks of cell treatment once per week with 2 * 10(6) cells, biochemical
      analysis of the serum and histopathological analysis of the liver tissue were
      performed. The results of the biochemical analysis of the serum show that the
      hHGF-HUCB-MSC-treated group had higher levels of alanine aminotransferase,
      aspartate aminotransferase and alkaline phosphatase, indicating the improvement
      of liver function. Histopathology showed that the hHGF-HUCB-MSC-treated group had
      reduction in the density of collagen fibres. Thus hHGF-HUCB-MSCs can enhance
      liver regeneration and could be useful for the treatment of patients with liver
      fibrosis or cirrhosis.

PMID- 24115682
TI  - Intermittent X-linked thrombocytopenia with a novel WAS gene mutation.
AB  - X-linked thrombocytopenia (XLT) is caused by mutations in the WAS gene and
      characterized by thrombocytopenia with minimal or no immunodeficiency. Patients
      with XLT usually exhibit persistent thrombocytopenia, and intermittent
      thrombocytopenia has been described only in two families. Here, we report a
      patient with intermittent XLT carrying a novel missense mutation (Ala56Thr). He
      showed residual expression of Wiskott-Aldrich syndrome protein in the lymphocytes
      and platelets. There appeared to be an association between normal platelet
      numbers and a post infectious state. Our findings further support the importance
      of analysis of Wiskott-Aldrich syndrome protein in male patients who exhibit
      fluctuating courses of thrombocytopenia.

PMID- 24115683
TI  - The particle size dependence of the oxygen reduction reaction for carbon
      supported platinum and palladium.
AB  - Model carbon supported Pt and Pd electrocatalysts have been prepared using a high
      throughput physical vapor deposition method. For Pt, metal particle sizes are
      controlled between 1.5-5.5 nm over 100 electrodes of an electrochemical screening
      chip, allowing the oxygen reduction reaction (ORR) activity of the catalysts to
      be determined simultaneously. The ORR-specific current density is observed to
      increase with increasing particle diameter up to approximately 4 nm, at which
      point the activity begins to level off. The reduction in ORR activity for
      particles below 4 nm is accompanied by a concomitant increase in the
      overpotential for surface reduction. The resulting mass activity exhibits a
      maximum for particles with diameters of approximately 3.5 nm. These results are
      consistent with results published recently for high area carbon-supported Pt
      catalysts. For Pd particles, both the specific current density and the mass
      specific activity for the ORR are observed to increase with increasing particle
      diameter, with no distinct optimum observed. The implications for the
      optimization of Pt- or Pd-based ORR catalysts for proton exchange membrane fuel
      cell (PEMFC) applications are discussed.

PMID- 24115684
TI  - A genome wide survey supports the involvement of large copy number variants in
      schizophrenia with and without intellectual disability.
AB  - BACKGROUND: Copy number variants (CNVs) have been shown to play a role in
      schizophrenia and intellectual disability. METHODS: We compared the CNV burden in
      66 patients with intellectual disability and no symptoms of psychosis (ID-only)
      with the burden in 64 patients with intellectual disability and schizophrenia (ID
      + SCZ). Samples were genotyped on three plates by the Broad Institute using the
      Affymetrix 6.0 array. RESULTS: For CNVs larger than 100 kb, there was no
      difference in the CNV burden of ID-only and ID + SCZ. In contrast, the number of
      duplications larger than 1 Mb was increased in ID + SCZ compared to ID-only. We
      detected seven large duplications and two large deletions at chromosome 15q11.2
      (18.5-20.1 Mb) which were all present in patients with ID + SCZ. The involvement
      of this region in schizophrenia was confirmed in Scottish samples from the ISC
      study (N = 2,114; 1,130 cases and 984 controls). Finally, one of the patients
      with schizophrenia and low IQ carrying a duplication at 15q11.2, is a member of a
      previously described pedigree with multiple cases of mild intellectual
      disability, schizophrenia, hearing impairment, retinitis pigmentosa and
      cataracts. DNA samples were available for 11 members of this family and the
      duplication was present in all 10 affected individuals and was absent in an
      unaffected individual. CONCLUSIONS: Duplications at 15q11.2 (18.5-20.1 Mb) are
      highly prevalent in a severe group of patients characterized by intellectual
      disability and comorbid schizophrenia. It is also associated with a phenotype
      that includes schizophrenia, low IQ, hearing and visual impairments resembling
      the spectrum of symptoms described in "ciliopathies."

PMID- 24115685
TI  - Synthesis and properties of alkoxy- and alkenyl-substituted peralkylated
      imidazolium ionic liquids.
AB  - Novel peralkylated imidazolium ionic liquids bearing alkoxy and/or alkenyl side
      chains have been synthesized and studied. Different synthetic routes towards the
      imidazoles and the ionic liquids comprising bromide, iodide, methanesulfonate,
      bis(trifluoromethylsulfonyl)imide ([NTf2](-)), and dicyanamide {[N(CN)2](-)} as
      the anion were evaluated, and this led to a library of analogues, for which the
      melting points, viscosities, and electrochemical windows were determined.
      Incorporation of alkenyl moieties hindered solidification, except for cations
      with high symmetry. The alkoxy-derivatized ionic liquids are often crystalline;
      however, room-temperature ionic liquids (RTILs) were obtained with the weakly
      coordinating anions [NTf2](-) and [N(CN)2](-). For the viscosities of the
      peralkylated RTILs, an opposite trend was found, that is, the alkoxy derivatives
      are less viscous than their alkenyl-substituted analogues. Of the crystalline
      compounds, X-ray diffraction data were recorded and related to their molecular
      properties. Upon alkoxy substitution, the electrochemical cathodic limit
      potential was found to be more positive, whereas the complete electrochemical
      window of the alkenyl-substituted imidazolium salts was shifted to somewhat more
      positive potentials.

PMID- 24115686
TI  - UK multicenter experience using the Gore septal occluder (GSO(TM) ) for atrial
      septal defect closure in children and adults.
AB  - BACKGROUND: Percutaneous closure of atrial defects (ASD) has evolved as the
      treatment of choice for the majority of defects and patent oval foramens. The
      Gore Septal Occluder (GSO) is an innovative device consisting mostly of a folded
      thin GoreTex tube for use in the closure of septal defects. METHODS: Reviewed is
      the multicenter UK experience of the first 22 ASD occlusions with the GSO(TM)
      device. All implantations were performed by consultant operators experienced in
      ASD device closure. The inclusion criterion was the presence of a hemodynamically
      significant secundum ASD with a diameter of <18 mm. Procedural data and acute and
      mid-term closure rates were retrospectively matched to a cohort of patients
      having defect closure using the Amplatzer Septal Occluder(TM) (ASO(TM) ).
      RESULTS: Acute and 3-month follow-up closure rates for the GSO(TM) were 100% and
      100% vs. 100% and 100% closure with the ASO(TM) implants. The difference in
      paired procedure times was not statistically significant (56 min: GSO(TM) ; 42
      min: ASO(TM) device P = ns), nor was the paired difference in fluoroscopic
      screening times (12 min: GSO(TM) vs. 8.4 min: ASO(TM) , P = ns). One GSO device
      embolized immediately after deployment and was successfully retrieved at the same
      procedure. There were no other significant complications in either group.
      CONCLUSIONS: The GSO(TM) implant can achieve comparable closure rates to the
      ASO(TM) in small to moderate atrial septal defects after 3 months. Longer
      fluoroscopy and procedure times are a drawback; however these should improve with
      familiarity with the implant and deployment system. The larger sheath size was
      not associated with increased complications in our cohort.

PMID- 24115687
TI  - Mass spectrometry-based proteomic analysis of Leishmania donovani soluble
      proteins in Indian clinical isolate.
AB  - Leishmania donovani, a causative organism of visceral leishmaniasis (VL), is
      responsible for high mortality throughout the world. Due to the unsatisfactory
      treatment measures and increasing drug resistance, there has been an urgent need
      to develop novel drug/vaccine targets against VL. The aim of this study was to
      identify novel targets in soluble L. donovani (SLD) protein. SLD protein was
      isolated and resolved by two-dimensional gel electrophoresis and analyzed through
      MALDI-TOF/TOF-based mass spectrometry. Proteomic results identified several
      proteins as drug targets, Th1 stimulatory, novel, and hypothetical proteins which
      could have crucial biological functions in Leishmania pathogenesis.

PMID- 24115688
TI  - Effect of geometry and microstructure of honeycomb TCP scaffolds on bone
      regeneration.
AB  - In recent years, artificial biological materials have been commonly used for the
      treatment of bone tissue defects caused by trauma, tumors, or surgical stress.
      Although tricalcium phosphate (TCP) is a promising absorbent bone tissue
      reconstruction biomaterial, it has been reported that its biocompatibility and
      osteoconductivity depend on its preparation method and sintering temperature. In
      addition, although it is thought that the microenvironment produced by the
      extracellular matrix plays an important role in cell growth and differentiation,
      there have been few studies on how the geometric structure of artificial
      biological materials affects cells. In the present study, a new honeycomb TCP
      scaffold containing through-holes with diameters of 300 um has been developed.
      The influence of the sintering temperature on the crystal structure and material
      properties of the honeycomb TCP scaffold was investigated using scanning electron
      microscopy and X-ray diffraction. Its biocompatibility and osteoconductivity were
      also evaluated by implantation into experimental animals. It was found that a
      beta-TCP scaffold sintered at 1200 degrees C exhibited high biocompatibility and
      osteoconductivity, and when it was loaded with BMP-2, it exhibited both
      osteoconductivity and osteoinductivity, promoting rapid bone formation in both
      ectopic and orthotopic areas. It is thus a highly promising bone reconstruction
      material that is expected to find clinical applications.

PMID- 24115689
TI  - Modulating the rotation of a molecular rotor through hydrogen-bonding
      interactions between the rotator and stator.

PMID- 24115691
TI  - Nursing-the supply side.

PMID- 24115690
TI  - Gadolinium-conjugated gold nanoshells for multimodal diagnostic imaging and
      photothermal cancer therapy.
AB  - Multimodal imaging offers the potential to improve diagnosis and enhance the
      specificity of photothermal cancer therapy. Toward this goal, gadolinium
      conjugated gold nanoshells are engineered and it is demonstrated that they
      enhance contrast for magnetic resonance imaging, X-ray, optical coherence
      tomography, reflectance confocal microscopy, and two-photon luminescence.
      Additionally, these particles effectively convert near-infrared light to heat,
      which can be used to ablate cancer cells. Ultimately, these studies demonstrate
      the potential of gadolinium-nanoshells for image-guided photothermal ablation. 

PMID- 24115692
TI  - Picking up the dropped bedpan - how our leadership can transform patient care.

PMID- 24115693
TI  - Paternity leave experiences of NHS doctors.
AB  - This study assesses NHS doctors' experiences of paternity leave and evaluates
      whether practices have changed since the introduction of additional paternity
      leave (APL) in April 2011. An anonymised online survey designed to discover
      experiences and uptake of APL and ordinary paternity leave (OPL) was distributed
      to all members of the London Deanery Synapse(r) network. In total, 364 fathers
      responded. Their seniority ranged from foundation trainees to consultants.
      Following the formal introduction of OPL in 2003, the number of fathers taking
      any paternity leave increased (from 50% to 95.6%). The majority of respondents
      (76.7%) felt well supported by their employer. Since the introduction of APL, 3%
      of respondents took additional leave. Reasons for the low uptake of APL included
      the impracticalities of the law, poor awareness and perceived attitudes and
      implications for training. Problems with OPL included the inadequate provision of
      cover and difficulties in timing the leave appropriately. 

PMID- 24115694
TI  - Report of a Royal College of Physicians and National Institute for Health
      Research workshop - developing research capacity to ensure successful study
      development and delivery.
AB  - The landscape and opportunities for clinical research have changed significantly
      following the creation of the National Institute for Health Research (NIHR) in
      2006. This article describes the scale and impact of the NIHR network
      infrastructure for clinical research and identifies areas for future development
      in partnership with the National Health Service (NHS), clinicians and research
      funders. 

PMID- 24115695
TI  - Training in general medicine - are juniors getting enough experience?
AB  - There is a widespread perception that trainees in medicine in the UK are 'not as
      good as they used to be' and reduction in hours of training is often cited as one
      cause. However, there are no data on the current experience of medical trainees
      in general medicine. The experience of foundation year doctors (FY1/2) and core
      medical trainees (CTs) in the management of 10 common medical conditions, eight
      common medical procedures and other aspects of medical training were collected by
      national survey in 2011. Trainees reported finding out-of-hours care the best
      setting for acute general medical experience and that the medical registrar was a
      key part of training. There was a significant lack of experience in both the
      management of medical conditions and the use of common procedures. These results
      highlight the challenges in general medical training and show that there is
      substantial room for improvement. 

PMID- 24115696
TI  - Neurology on the move?
AB  - This paper describes the unsatisfactory situation that currently affects the
      provision of neurological services in parts of England, as identified in three
      recent reports, and contains a number of suggested ways in which the situation
      might be improved, while highlighting the good work being done by specialist
      nurses and therapists and by the Neurological Alliance on behalf of patients and
      their families. 

PMID- 24115697
TI  - Neurology in motion.

PMID- 24115698
TI  - National sentinel stroke audit 1998-2011.
AB  - Stroke is a common and devastating disease and, until very recently, was largely
      unrecognised as a -preventable or treatable condition. Between 1998 and 2010, the
      National Sentinel Stroke Audit (NSSA) achieved 100% voluntary participation,
      collecting data on more than 60,000 patients from stroke services within England,
      Wales and Northern Ireland and becoming a benchmark for hospital stroke services.
      In this way it has informed stroke improvement at the local, regional and
      national levels and has overseen a radical change in stroke care within the NHS.
      This article describes the achievements of the NSSA and the -lessons learned. 

PMID- 24115699
TI  - Providing accurate information to patients who develop deep vein thrombosis.
AB  - Venous thromboembolism is an increasingly recognised complication in the
      community and in hospital in-patients. Nowadays, most physicians are familiar
      with the algorithmic approach to the management of suspected deep vein
      thrombosis. However, a lack of understanding remains with regard to certain
      aspects of the diagnostic and treatment pathways, which has resulted in the wrong
      information being imparted to patients. Some of these issues are discussed in
      this paper, with considerations for changes in management. 

PMID- 24115700
TI  - Developing a 'pleural team' to run a reactive pleural service.
AB  - Pleural disease is increasingly recognised as an important subspecialty within
      respiratory medicine, especially as cases of pleural disease continue to rise
      internationally. Recent advances have seen an expansion in the options available
      for managing patients with pleural disease, with access to local-anaesthetic
      thoracoscopy, indwelling pleural catheters and thoracic ultrasound all becoming
      commonplace. Pleural teams usually consist of a range of practitioners who can
      optimise the use of specialist services to ensure that patients with all types of
      pleural disease - who have traditionally needed extended admissions - are managed
      efficiently, often entirely as outpatients. A pleural service can also provide
      improved opportunities for enhancing procedural skills, engaging in clinical
      research, and reducing the costs of care. This article explores the justification
      for dedicated pleural services and teams, as well as highlighting the various
      roles of hospital personnel who might be most useful in ensuring their success. 

PMID- 24115701
TI  - The burden of cancer on the acute medical unit.
AB  - The burden of cancer is increasing, with a significant increase in cancer-related
      emergencies and patients with known malignancy presenting to the acute medical
      unit (AMU). We performed a retrospective analysis at a university hospital in the
      north west of England in May 2011. We examined 300 consecutive admissions to
      determine the number of, and reason for, cancer patients presenting to the AMU.
      Patients with cancer had a statistically significantly longer average length of
      inpatient stay than patients without cancer (8.8 days vs 7.2 days, p<0.01). As
      the incidence and prevalence of cancer increases, the challenge of improving the
      experience, safety and outcomes of patients with cancer becomes more important.
      Development of successful acute oncology services with close working with acute
      physicians will be essential in order to achieve this. 

PMID- 24115702
TI  - Diabetes and renal disease: who does what?
AB  - Care of patients with diabetes and chronic kidney disease (CKD) in the UK is
      divided between primary care, diabetologists and nephrology. In a retrospective
      analysis, we examined the distribution of care provision for patients with
      diabetes and CKD. Nephrology services see a minority of diabetic patients with
      CKD, but they see the majority of those with an estimated glomerular filtration
      rate (eGFR) of <30 ml/min. Of those followed in nephrology, 70% showed no
      evidence of progressive renal dysfunction. The nephrology cohort were
      significantly younger that those seen by primary care physicians or
      diabetologists. Half of the patients with diabetes and CKD seen in either the
      primary care and diabetology cohorts, with no nephrology input, had a rate of
      fall of eGFR of >5 ml/min/yr. This suggests that older age might deter referral
      to nephrology, which is based predominantly on CKD stage. This results in a
      significant proportion of patients with stable renal function being seen by
      nephrology, and in the under-referral of a large cohort of patients with
      progressive CKD. 

PMID- 24115703
TI  - Computed tomographic coronary angiography - is it ready as a screening tool for
      coronary artery disease?
AB  - Currently, there are no formal screening programmes for coronary artery disease
      (CAD). Computed tomographic coronary angiography (CTCA) has been suggested as a
      non-invasive and reliable method of atherosclerotic plaque assessment, with the
      potential for use in screening programmes. In this article, we briefly present
      the current understanding of atherosclerotic plaque formation, explain key
      technological aspects of CTCA and critique this method in the light of World
      Health Organisation (WHO) criteria for devising a screening programme. Current
      evolving and future insights are also considered. Overall, in our view, there is
      currently insufficient evidence to support the formal use of CTCA in a screening
      programme for CAD, although this viewpoint will undoubtedly evolve. 

PMID- 24115704
TI  - Obesity: a window of opportunity to intervene? Characteristics and management of
      morbidly obese adult inpatients in three trusts in Southern England.
AB  - Obesity affects 22% of men and 24% of women over the age of 16 years in the
      general population of the UK and is associated with multiple comorbidities.
      Little is known about the magnitude of the obesity problem among hospitalised
      adults and, although significant focus has been given to the identification and
      treatment of the malnourished inpatient, it is not known to what extent obese
      inpatients are equally -targeted. National guidelines for consideration of
      bariatric surgery exist, but it is not known to what extent potentially eligible
      individuals are referred. This multi-centre study -demonstrates a significant
      burden of obesity (defined as body mass index [BMI] >=30 kg/m(2)) among those in
      hospital, affecting 22% of patients. This was more marked among orthopaedic
      patients and all-comers to intensive care units than on medical or surgical
      wards. Of those with BMI >=35 kg/m(2), only 21% had been reviewed by dietetics
      and only 10% of patients who were potentially eligible for bariatric surgery had
      been referred to bariatric services. This study shows that there is an
      opportunity to recognise obesity and intervene in its management during hospital
      admission. 

PMID- 24115705
TI  - Recent changes in the drug treatment of allergic asthma.
AB  - Asthma is a heterogeneous condition with multiple phenotypes that respond to
      treatments in different ways. Allergic asthma is an important phenotype and
      although currently available treatments are effective, about 5% of affected
      patients have severe, treatment-refractory disease. Despite advances in our
      understanding of the disease, there remains an unmet need in this group of
      patients. The most recent and significant advance in treatment has been anti-
      immunoglobulin E (IgE) therapy, which improves symptoms and quality of life in
      patients with severe allergic asthma. Clinical trials are ongoing with novel
      biologic agents that demonstrate potential efficacy; determining the subsets of
      patients for which they are suitable will be crucial to ensure cost
      effectiveness. Personalised medicine and targeted therapies may hold the key to
      long-term control in this group of patients. 

PMID- 24115706
TI  - Coming of age in cystic fibrosis - transition from paediatric to adult care.
AB  - Cystic fibrosis (CF) is the most common multi-system inherited disorder, with a
      UK population exceeding 9,000. There have been significant improvements in CF
      survival over the decades, attributed to improvements in therapies available, our
      understanding of the disease and better organisation of care. CF care providers
      have been early advocates for successful healthcare transition from the
      paediatric to adult sector and CF can be considered a model process where a
      paediatric disease has now become an adult one. This article looks at the
      transition process in CF and the future challenges CF physicians will face. 

PMID- 24115707
TI  - Comparative studies and healthcare policy: learning and mislearning across
      borders.
AB  - This article addresses the vocabulary of cross-national analysis and commentary
      about health care, health policy and health politics. We conclude there is a
      large gap between promise and performance in comparative policy commentary and
      point to major sources of confusion, such as the lack of generally agreed
      vocabulary, vague language and the use of faddish and misleading terms and
      aspirational labels (illustrated by a selection of widely used expressions in
      comparative reports). We next examine the basic purposes of international policy
      comparison, distinguish three useful and two misleading approaches and frame
      defensible ground rules for comparative work. 

PMID- 24115708
TI  - Sleep medicine - prevalent and relevant.
AB  - There is an increasing awareness of different sleep disorders among the public
      and healthcare professionals, and the impact they can have on an individual. This
      conference was organised jointly with the British Thoracic Society to discuss
      some of these pertinent conditions, issues around driving and around service
      planning to accommodate an increasing specialty. 

PMID- 24115709
TI  - Outpatient parenteral antimicrobial therapy (OPAT) and the general physician.

PMID- 24115710
TI  - Antibiotic stewardship.

PMID- 24115711
TI  - Atypical mycobacteria: an important differential for the general physician.

PMID- 24115712
TI  - Invasive fungal infections.

PMID- 24115713
TI  - Acute infections in intravenous drug users.

PMID- 24115715
TI  - A catastrophic cause of chest pain.
AB  - Chest pain can be a manifestation of aortic pathology and must be considered in
      any patient with a history of chest trauma, hypertension, atherosclerosis,
      connective tissue disorder and/or radiographically abnormal aortic contours.
      Acute intramural haematoma can resemble acute myocardial infarction and can be
      life-threatening if not correctly diagnosed. Electrocardiogram (ECG) must be
      carried out in all patients as it helps distinguish acute myocardial infarction
      (for which antiplatelets and anticoagulants may be life-saving) from intramural
      haematoma (for which these drugs may be detrimental). Other imaging modalities
      may be considered depending upon the clinical situation. 

PMID- 24115716
TI  - A young man with a dizzy spell and acute abdominal pain.
AB  - Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare cause of
      secondary adrenal insufficiency and its presentation with adrenal crisis is
      rather rare. Acute adrenal insufficiency (adrenal crisis) can be an elusive
      diagnosis, particularly in previously undiagnosed patients. As in this patient,
      the presentation of adrenal crisis with acute abdominal pain was misdiagnosed as
      an acute surgical abdomen, leading to a delay in the diagnosis and in the
      initiation of life saving treatment. 

PMID- 24115717
TI  - An unusual cause of vomiting.

PMID- 24115719
TI  - Severe hypercalcaemia can be due to benign disease and give reversible
      neurological signs.

PMID- 24115720
TI  - Laboratory samples deemed 'unsuitable for analysis' can be diagnostically useful.

PMID- 24115721
TI  - Is research declining among gastroenterology trainees in the UK.

PMID- 24115722
TI  - PEG placement for patients with oropharyngeal/oeosphageal cancers.

PMID- 24115723
TI  - Managing hyperglycaemic emergencies: an illustrative case and review of recent
      British guidelines.

PMID- 24115724
TI  - Nasogastric feeding tubes - algorithm for correct placement.

PMID- 24115725
TI  - Target hopping as a useful tool for the identification of novel EphA2 protein
      protein antagonists.
AB  - Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and
      the G-protein-coupled receptor TGR5, has been recently described as an antagonist
      of the EphA2 receptor, a key member of the ephrin signalling system involved in
      tumour growth. Given the ability of LCA to recognize FXR, TGR5, and EphA2
      receptors, we hypothesized that the structural requirements for a small molecule
      to bind each of these receptors might be similar. We therefore selected a set of
      commercially available FXR or TGR5 ligands and tested them for their ability to
      inhibit EphA2 by targeting the EphA2-ephrin-A1 interface. Among the selected
      compounds, the stilbene carboxylic acid GW4064 was identified as an effective
      antagonist of EphA2, being able to block EphA2 activation in prostate carcinoma
      cells, in the micromolar range. This finding proposes the "target hopping"
      approach as a new effective strategy to discover new protein-protein interaction
      inhibitors. 

PMID- 24115726
TI  - Rotational and translational dynamics of ras proteins upon binding to model
      membrane systems.
AB  - Plasma-membrane-associated Ras proteins typically control signal transduction
      processes. As nanoclustering and membrane viscosity sensing provide plausible
      signaling mechanisms, determination of the rotational and translational dynamics
      of membrane-bound Ras isoforms can help to link their dynamic mobility to their
      function. Herein, by using time-resolved fluorescence anisotropy and correlation
      spectroscopic measurements, we obtain the rotational-correlation time and the
      translational diffusion coefficient of lipidated boron-dipyrromethene-labeled
      Ras, both in bulk Ras and upon membrane binding. The results show that the second
      lipidation motif of N-Ras triggers dimer formation in bulk solution, whereas K
      Ras4B is monomeric. Upon membrane binding, an essentially free rotation of the G
      domain is observed, along with a high lateral mobility; the latter is essentially
      limited by the viscosity of the membrane and by lipid-mediated electrostatic
      interactions. This high diffusional mobility warrants rapid recognition-binding
      sequences in the membrane-bound state, thereby facilitating efficient
      interactions between the Ras proteins and scaffolding or effector proteins. The
      lipid-like rapid lateral diffusion observed here complies with in vivo data. 

PMID- 24115727
TI  - Aberrant activation, nuclear localization, and phosphorylation of Yes-associated
      protein-1 in the embryonic kidney and Wilms tumor.
AB  - BACKGROUND: The Yes-associated-protein-1 (YAP1) is a novel, direct regulator of
      stem cell genes both in development and cancer. FAT4 is an upstream regulator
      that induces YAP1 cytosolic sequestering by phosphorylation (p-Ser 127) and
      therefore inhibits YAP1-dependent cellular proliferation. We hypothesized that
      loss of FAT4 signaling would result in expansion of the nephron progenitor
      population in kidney development and that YAP1 subcellular localization would be
      dysregulated in Wilms tumor (WT), an embryonal malignancy that retains gene
      expression profiles and histologic features reminiscent of the embryonic kidney.
      METHODS: Fetal kidneys from Fat4(-/-) mice were harvested at e18.5 and markers of
      nephron progenitors were investigated using immunohistochemical analysis. To
      examine YAP1 subcellular localization in WT, a primary WT cell line (VUWT30) was
      analyzed by immunofluorescence. Forty WT specimens evenly distributed between
      favorable and unfavorable histology (n = 20 each), and treatment failure or
      success (n = 20 each) was analyzed for total and phosphorylated YAP1 using
      immunohistochemistry and Western blot. RESULTS: Fat4(-/-) mouse fetal kidneys
      exhibit nuclear YAP1 with increased proliferation and expansion of nephron
      progenitor cells. In contrast to kidney development, subcellular localization of
      YAP1 is dysregulated in WT, with a preponderance of nuclear p-YAP1. By Western
      blot, median p-YAP1 quantity was 5.2-fold greater in unfavorable histology WT (P
      = 0.05). CONCLUSIONS: Fetal kidneys in Fat4(-/-) mice exhibit a phenotype
      reminiscent of nephrogenic rests, a WT precursor lesion. In WT, YAP1 subcellular
      localization is dysregulated and p-YAP1 accumulation is a novel biomarker of
      unfavorable histology.

PMID- 24115729
TI  - Facilitated transport in hydroxide-exchange membranes for post-combustion CO2
      separation.
AB  - Hydroxide-exchange membranes are developed for facilitated transport CO2 in post
      combustion flue-gas feed. First, a correlation between the basicity of fixed-site
      functional groups and CO2 -separation performance is discovered. This
      relationship is used to identify phosphonium as a promising candidate to achieve
      high CO2 -separation performance. Consequently, quaternary phosphonium-based
      hydroxide-exchange membranes are demonstrated to have a separation performance
      that is above the Robeson upper bound. Specifically, a CO2 permeability as high
      as 1090 Barrer and a CO2 /N2 selectivity as high as 275 is achieved. The high
      performance observed in the membranes can be attributed to the quaternary
      phosphonium moiety.

PMID- 24115728
TI  - Mapping of genotype-phenotype diversity among clinical isolates of mycobacterium
      tuberculosis by sequence-based transcriptional profiling.
AB  - Genome sequencing has identified an extensive repertoire of single nucleotide
      polymorphisms among clinical isolates of Mycobacterium tuberculosis, but the
      extent to which these differences influence phenotypic properties of the bacteria
      remains to be elucidated. To determine whether these polymorphisms give rise to
      phenotypic diversity, we have integrated genome data sets with RNA sequencing to
      assess their impact on the comparative transcriptome profiles of strains
      belonging to M. tuberculosis Lineages 1 and 2. We observed clear correlations
      between genotype and transcriptional phenotype. These arose by three mechanisms.
      First, lineage-specific changes in amino acid sequence of transcriptional
      regulators were associated with alterations in their ability to control gene
      expression. Second, changes in nucleotide sequence were associated with
      alteration of promoter activity and generation of novel transcriptional start
      sites in intergenic regions and within coding sequences. We show that in some
      cases this mechanism is expected to generate functionally active truncated
      proteins involved in innate immune recognition. Finally, genes showing lineage
      specific patterns of differential expression not linked directly to primary
      mutations were characterized by a striking overrepresentation of toxin-antitoxin
      pairs. Taken together, these findings advance our understanding of mycobacterial
      evolution, contribute to a systems level understanding of this important human
      pathogen, and more broadly demonstrate the application of state-of-the-art
      techniques to provide novel insight into mechanisms by which intergenic and
      silent mutations contribute to diversity. 

PMID- 24115730
TI  - Evolution of musculoskeletal ultrasound in the United States: implementation and
      practice in rheumatology.

PMID- 24115731
TI  - Phase II trial of clofarabine with topotecan, vinorelbine, and thiotepa in
      pediatric patients with relapsed or refractory acute leukemia.
AB  - BACKGROUND: Outcomes for children with relapsed/refractory (R/R) acute
      lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are dismal. In
      an effort to improve outcomes, we performed a phase I/II study of a novel
      clofarabine based combination regimen called TVTC. Herein, we report the response
      rates of patients in the phase II portion of the study. PROCEDURE: Seventeen
      patients with R/R ALL, AML, or biphenotypic leukemia were enrolled. Sixteen
      patients were evaluable for response. Patients were treated at the maximum
      tolerated dose (MTD) from the phase I portion of the study (clofarabine 40
      mg/m(2) /day IV * 5 days, topotecan 1 mg/m(2) /day IV continuous infusion * 5
      days, vinorelbine 20 mg/m(2) /week IV * 3 weeks, thiotepa 15 mg/m(2)/day IV * 1
      day). The primary endpoint was overall response rate (ORR), defined as CR or CR
      without platelet recovery (CRp). RESULTS: The ORR was 69% (10 CR, 1 CRp). Among
      the 11 responders, 9 (82%) proceeded to hematopoietic stem cell transplantation.
      The most common grade 3+ non-hematologic toxicities were febrile neutropenia
      (82%) and transient transaminase elevation (47%). CONCLUSIONS: TVTC demonstrates
      significant activity in patients with R/R acute leukemia. The activity in R/R AML
      patients was very encouraging, with 8 of 12 (67%) patients achieving a CR/CRp.
      Patients with high risk de novo AML may benefit from incorporation of TVTC
      therapy into frontline treatment regimens. This regimen warrants further
      exploration in a larger cohort of patients with R/R leukemia.

PMID- 24115732
TI  - Shape-controlled ceria-based nanostructures for catalysis applications.
AB  - Among oxide catalysts, ceria is a technologically important material because of
      its wide applications as a promoter in three-way catalysts for the elimination of
      toxic exhaust gases, low-temperature water-gas-shift reaction, oxygen sensors,
      oxygen permeation membrane systems, and fuel cells. The catalytic activities of
      cerium oxide are highly dependent on interfacial structures and nanocrystal
      morphologies. This Minireview highlights the recent progress in the research of
      ceria nanoshapes as both catalysts and catalyst supports, including the
      synthesis, structure characterization, catalytic properties, surface chemistry,
      as well as reaction mechanisms. Insights from in situ spectroscopy study and
      theoretical modeling of nanostructured ceria-based materials have shed light on
      the origin of the ceria shape effect. It is suggested that the surface structure
      of ceria controls the catalytic activity and selectivity through structure
      dependent surface-site geometry, surface vacancy formation energy, defect sites,
      and coordinatively unsaturated sites on ceria. The morphology-dependent catalysis
      in ceria has offered a new strategy to finely tune the catalytic activity and
      selectivity through shape control without altering the catalyst composition. A
      brief summary and an outlook on this research field will be presented at the end.

PMID- 24115733
TI  - Synthesis and biological evaluation of imidazopyridine-oxindole conjugates as
      microtubule-targeting agents.
AB  - A library of imidazopyridine-oxindole conjugates was synthesised and investigated
      for anticancer activity against various human cancer cell lines. Some of the
      tested compounds, such as 10 a, 10 e, 10 f, and 10 k, exhibited promising
      antiproliferative activity with GI50 values ranging from 0.17 to 9.31 MUM. Flow
      cytometric analysis showed that MCF-7 cells treated by these compounds arrested
      in the G2 /M phase of the cell cycle in a concentration-dependent manner. More
      particularly, compound 10 f displayed a remarkable inhibitory effect on tubulin
      polymerisation. All the compounds depolarised mitochondrial membrane potential
      and caused apoptosis. These results are further supported by the decreased
      phosphorylation of Akt at Ser473. Studies on embryonic development revealed that
      the lead compounds 10 f and 10 k caused delay in the development of zebra fish
      embryos. Docking of compound 10 f with tubulin protein suggested that the
      imidazo[1,2-a]pyridine moiety occupies the colchicine binding site of tubulin. 

PMID- 24115734
TI  - The effect of cell subset isolation method on gene expression in leukocytes.
AB  - Multiple scientific disciplines require the isolation of specific subsets of
      blood cells from patient samples for gene expression analysis by microarray or
      RNA-sequencing, preserving disease- or treatment-related signatures. However,
      little is known with respect to the impact of different cell isolation methods on
      gene expression and the effects of positive selection, negative selection, and
      fluorescence activated cell sorting (FACS) have not previously been assessed in
      parallel. To address this knowledge gap, CD4+ T cells, CD8+ T cells, B cells, and
      monocytes were isolated from blood samples from five independent donors using
      positive immunomagnetic selection, negative immunomagnetic selection, and FACS.
      We hypothesized that positive selection and FACS would yield higher purity but
      may have an impact on gene expression since both methods utilize antibodies that
      bind surface receptors of the cell type of interest. Moreover, FACS might
      upregulate stress response genes due to passage of the cells through the sorter.
      Microarray gene expression data were generated and subjected to unsupervised
      clustering and differential gene expression analysis. Surprisingly, these
      analyses revealed that gene expression signatures were more similar between cells
      isolated by negative selection and FACS compared to cells isolated by positive
      selection. Moreover, genes that are involved in the response to stress generally
      had the highest expression in cells isolated by negative or positive selection
      and not FACS. Thus, FACS is the recommended method for isolation of leukocyte
      subsets for gene expression studies since this method results in the purest
      subset populations and does not appear to induce a stress response.

PMID- 24115735
TI  - A risk algorithm for assessing short-term mortality for obese black and white men
      and women.
AB  - OBJECTIVE: To develop and validate a mortality risk algorithm for obese black and
      white men and women to elucidate risk factors prognostic of short-term mortality
      among obese persons. METHODS: Prospective cohort study. Reasons for geographic
      and racial differences in stroke (REGARDS) study, is a cohort of black and white
      men and women aged >=45 years. Obese (>=30 kg m(-2) ) participants in REGARDS (n
      = 11 288) were randomly assigned to the derivation data set or an independent
      validation set. RESULTS: During the mean follow-up period of 4.9 years, 8.9% (n =
      504) in the derivation cohort and 8.7% (n = 492) in the validation cohort died.
      The best-fitting model based on data from the derivation cohort included
      demographic (age, sex), coronary heart disease (CHD) conditions (diabetes,
      systolic blood pressure, history of CHD), health behaviors (smoking, physical
      activity, alcohol use), and socioeconomic variables (income, use of physician
      services). The C-statistic when the model was applied to the validation cohort
      was 0.80. Observed and predicted rates of mortality were similar across deciles
      of mortality risk by race. CONCLUSIONS: A risk algorithm was established and
      validated to predict mortality among black and white obese subjects based on CHD
      risk factors, behavioral risk factors, and socioeconomic status.

PMID- 24115736
TI  - Photocatalytic hydrogen evolution with a hydrogenase in a mediator-free system
      under high levels of oxygen.
AB  - Take a breath: An oxygen-tolerant hydrogenase can be employed with a dye in a
      photocatalytic scheme for the generation of H2 . The homogeneous system does not
      require a redox mediator and visible-light irradiation yields high amounts of H2
      even in the presence of air. 

PMID- 24115737
TI  - Surface reconstruction and hemocompatibility improvement of a phosphorylcholine
      end-capped poly(butylene succinate) coating.
AB  - Control over cell-material surface interactions is the key to many new and
      improved biomedical devices. In this study, we present a simple yet effective
      surface modification method that allows for the surface reconstruction and
      formation of cell outer membrane mimetic structure on coatings that have
      significantly increased hemocompatibility. To achieve this, a phosphorylcholine
      end-capped poly(butylene succinate) (PBS-PC) was synthesized and dip-coated on
      coverslips. The surface structure of the amphiphilic PBS-PC film was
      reconstructed by heating in a vacuum oven to obtain the less hydrophilic surface
      and by immersing in hot water to obtain the more hydrophilic surface. Significant
      changes in the surface element concentration were observed by X-ray photoelectron
      spectroscopy analysis and changes in surface wettability were measured by
      sensitive dynamic contact angle technique. Scanning electron microscope images
      showed different morphologies of the reconstructed surfaces. Interestingly, the
      reconstruction between the less hydrophilic and more hydrophilic surfaces is
      reversible. More importantly, both the reconstructed surfaces are stable in room
      condition for more than 6 months, and both the surfaces show significant
      improvement in hemocompatibility as revealed by protein adsorption and platelet
      adhesion measurements. This reversible surface reconstruction strategy and the
      interesting results may be significant for fabricating stable and hemocompatible
      surfaces on differently shaped biomedical devices.

PMID- 24115738
TI  - Nanobodies and nanocrystals: highly sensitive quantum dot-based homogeneous FRET
      immunoassay for serum-based EGFR detection.
AB  - Semiconductor quantum dot nanocrystals (QDs) for optical biosensing applications
      often contain thick polyethylene glycol (PEG)-based coatings in order to retain
      the advantageous QD properties in biological media such as blood, serum or
      plasma. On the other hand, the application of QDs in Forster resonance energy
      transfer (FRET) immunoassays, one of the most sensitive and most common
      fluorescence-based techniques for non-competitive homogeneous biomarker
      diagnostics, is limited by such thick coatings due to the increased donor
      acceptor distance. In particular, the combination with large IgG antibodies
      usually leads to distances well beyond the common FRET range of approximately 1
      to 10 nm. Herein, time-gated detection of Tb-to-QD FRET for background
      suppression and an increased FRET range is combined with single domain antibodies
      (or nanobodies) for a reduced distance in order to realize highly sensitive QD
      based FRET immunoassays. The "(nano)(2) " immunoassay (combination of
      nanocrystals and nanobodies) is performed on a commercial clinical fluorescence
      plate reader and provides sub-nanomolar (few ng/mL) detection limits of soluble
      epidermal growth factor receptor (EGFR) in 50 MUL buffer or serum samples. Apart
      from the first demonstration of using nanobodies for FRET-based immunoassays, the
      extremely low and clinically relevant detection limits of EGFR demonstrate the
      direct applicability of the (nano)(2-) assay to fast and sensitive biomarker
      detection in clinical diagnostics. 

PMID- 24115740
TI  - 5-(2-Aminopropyl)indole (5-IT): a psychoactive substance used for recreational
      purposes is an inhibitor of human monoamine oxidase (MAO).
AB  - 5-(2-Aminopropyl)indole (5-IT) is a psychoactive compound that has recently been
      associated with several fatal and non-fatal intoxications in a number of European
      countries. There are indications that acute effects may include symptoms of
      monoaminergic (e.g. serotonin) toxicity and one mechanism involved in the
      increase of serotonin levels includes the inhibition of monoamine oxidase. This
      study investigated the effect of 5-IT on human MAO-A and -B isozymes using
      kynuramine as the substrate. Substrate conversion to 4-hydroxyquinoline was
      monitored by high-performance liquid chromatography coupled to diode array
      detection. This method was employed to determine the extent of MAO inhibition
      (IC50 and Ki ) and it was found that 5-IT was a selective, competitive and
      reversible inhibitor of MAO-A. 5-IT revealed a relatively potent ability to
      inhibit MAO-A (IC50  =1.6 MUM and Ki  =0.25 MUM) while MAO-B inhibition was not
      observed (0-500 MUM 5-IT). Under identical experimental conditions, other
      established inhibitors of MAO-A and antidepressants provided the following IC50
      values: clorgyline 16 nM, harmaline 20 nM, toloxatone 6.7 MUM and moclobemide
      >500 MUM. These data indicated that 5-IT was less potent than clorgyline and
      harmaline but more potent than toloxatone and moclobemide under the in-vitro
      conditions studied. The inhibition of MAO-A suggests that 5-IT by itself or in
      combination with other substances may be able to potentiate
      serotonergic/monoaminergic effects and further studies are needed to clarify its
      relevance to the adverse effects reported for 5-IT.

PMID- 24115739
TI  - Higher rates and clustering of abnormal lipids, obesity, and diabetes mellitus in
      psoriatic arthritis compared with rheumatoid arthritis.
AB  - OBJECTIVE: We compared the prevalence and the clustering of the metabolic
      syndrome (MetS) components (obese body mass index [BMI; >=30 kg/m(2) ],
      hypertriglyceridemia, low high-density lipids, hypertension, and diabetes
      mellitus) in patients with psoriatic arthritis (PsA) and rheumatoid arthritis
      (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA)
      Registry. METHODS: We included CORRONA participants with a rheumatologist
      confirmed clinical diagnosis of PsA or RA with complete data. We used a modified
      definition of MetS that did not include insulin resistance, waist circumference,
      or blood pressure measurements. Logistic regression models were adjusted for age,
      sex, and race. RESULTS: In the overall CORRONA population, the rates of diabetes
      mellitus and obesity were significantly higher in PsA compared with RA. In 294
      PsA and 1,162 RA participants who had lipids measured, the overall prevalence of
      MetS in PsA versus RA was 27% versus 19%. The odds ratio (OR) of MetS in PsA
      versus RA was 1.44 (95% confidence interval [95% CI] 1.05-1.96, P = 0.02). The
      prevalence of hypertriglyceridemia was higher in PsA compared with RA (38% versus
      28%; OR 1.51 [95% CI 1.15-1.98], P = 0.003). The prevalence of type 2 diabetes
      mellitus was also higher in PsA compared with RA (15% versus 11%; OR 1.56 [95% CI
      1.07-2.28], P = 0.02) in the adjusted model. Similarly, higher rates of
      hypertriglyceridemia and diabetes mellitus were observed in the subgroup of PsA
      and RA patients with obese BMI. CONCLUSION: Compared with RA, PsA is associated
      with higher rates of obesity, diabetes mellitus, and hypertriglyceridemia.

PMID- 24115741
TI  - Synthesis and structure-activity relationship studies of quinoxaline derivatives
      as aldose reductase inhibitors.
AB  - ARIs for diabetes: A series of 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid
      derivatives were designed and synthesized as inhibitors of aldose reductase (AR),
      a novel target for the treatment of diabetes complications. Most of the
      derivatives proved to be potent and selective, with IC50 values in the low
      nanomolar to micromolar range. 

PMID- 24115742
TI  - Intracellular microenvironment responsive polymers: a multiple-stage transport
      platform for high-performance gene delivery.
AB  - A new strategy for promoting endoplasmic gene delivery and nucleus uptake is
      proposed by developing intracellular microenvironment responsive biocompatible
      polymers. This delivery system can efficiently load and self-assemble nucleic
      acids into nano-structured polyplexes at a neutral pH, release smaller imidazole
      gene complexes from the polymer backbones at intracellular endosomal pH,
      transport nucleic acids into nucleus through intracellular environment responsive
      multiple-stage gene delivery, thus leading to a high cell transfection
      efficiency. 

PMID- 24115743
TI  - Pain characteristics and age-related pain trajectories in infants and young
      children with sickle cell disease.
AB  - BACKGROUND: The epidemiology of painful episodes in infants and younger children
      with SCD has not been well studied, particularly for pain managed at home.
      PROCEDURE: SCD infants identified by newborn screening were enrolled in a
      longitudinal observational study of pain symptoms requiring parents to report the
      presence or absence of pain daily. When sickle cell related-pain events occurred,
      pain occurrence, location, associated symptoms and the treatment provided also
      were reported. RESULTS: 103 children were enrolled at a median age of 7.2 months;
      50 had an SS genotype, 32 SC, 6 SB(0)thalassemia, and 15 SB(+)thalassemia.
      Parents/guardians reported for a median of 3.8 years (range 0.3-7.6 years)
      assessing pain for a total of 141,197 days, excluding any period of recurrent
      transfusions, with an additional 28,079 days of missing data (16%). Children had
      pain reported on 2,288 days (1.6%), representing 768 distinct episodes of pain,
      of which 108 required hospitalizations (14%). Pain locations and symptoms
      consistent with dactylitis were most prevalent (80%) in the 0-12 month age group,
      and became progressively less prevalent thereafter. Group-based trajectory
      modeling of pain episode or pain day frequency identified several trajectory
      groups with progressively older ages of peak pain frequency, which included 40
      45% of SS/SB(0)thalassemia and 10-12% of SC/SB(+)thalassemia children.
      CONCLUSIONS: Pain is relatively infrequent in SCD infants and young children and
      commonly managed at home. Analyses of longitudinal pain trajectories suggest
      several different pain trajectories, differing in their frequency, age of onset,
      and age at peak pain frequency with clinical implications for hydroxyurea
      management.

PMID- 24115744
TI  - Thermoelectric properties and electronic structure of the zintl-phase
      Sr(3)AlSb(3).
AB  - The Zintl-phase Sr3 AlSb3 , which contains relatively earth-abundant and nontoxic
      elements, has many of the features that are necessary for good thermoelectric
      performance. The structure of Sr3 AlSb3 is characterized by isolated anionic
      units formed from pairs of edge-sharing tetrahedra. Its structure is distinct
      from previously studied chain-forming structures, Ca3 AlSb3 and Sr3 GaSb3 , both
      of which are known to be good thermoelectric materials. DFT predicts a relatively
      large band gap in Sr3 AlSb3 (Eg ~1 eV) and a heavier band mass than that found in
      other chain-forming A3 MSb3 phases (A=Sr, Ca; M=Al, Ga). High-temperature
      transport measurements reveal both high resistivity and high Seebeck coefficients
      in Sr3 AlSb3 , which is consistent with the large calculated band gap. The
      thermal conductivity of Sr3 AlSb3 is found to be extremely low (~ 0.55 W mK(-1)
      at 1000 K) due to the large, complex unit cell (56 atoms per primitive cell).
      Although the figure of merit (zT) has not been optimized in the current study, a
      single parabolic band model suggests that, when successfully doped, zT~ 0.3 may
      be obtained at 600 K; this makes Sr3 AlSb3 promising for waste-heat recovery
      applications. Doping with Zn(2+) on the Al(3+) site has been attempted, but does
      not lead to the expected increase in carrier concentration. 

PMID- 24115745
TI  - LOX-1 regulates estrogenesis via intracellular calcium release from bovine
      granulosa cells.
AB  - Estradiol produced by ovarian granulosa cells triggers the luteinizing hormone
      surge which in turn initiates ovulation in female mammals. Disturbances in
      estradiol production from granulosa cells are a major reason for reproductive
      dysfunctions in dairy cows. Endogenous estradiol production might be altered by
      reactive oxygen species (ROS) such as oxidized low-density lipoprotein (ox-LDL).
      Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a
      receptor of ox-LDL, leads to increased estrogenesis in granulosa cells. This
      activity is mediated by calcium release from endoplasmic reticulum (ER)-dependent
      and ER-independent calcium pools. Inhibition of the LOX-1 signal transduction
      pathway is followed by mitochondrial alterations. The membrane potential DeltaPsi
      increases and the ROS production decreases in mitochondria after blocking LOX-1.
      Our data indicate that blocking the LOX-1 receptor signal pathway might be a
      promising way to improve steroid hormone concentrations in metabolically highly
      active female mammals and, therefore, to defend against reproductive dysfunctions
      in humans and animals.

PMID- 24115746
TI  - Reply: To PMID 23203723.

PMID- 24115747
TI  - Effects of dietary interventions on liver volume in humans.
AB  - OBJECTIVE: To compare effects of similar weight loss induced either by a short
      term low-carbohydrate or by a long-term hypocaloric diet, and to determine
      effects of high carbohydrate overfeeding on liver total, lean, and fat volumes.
      METHODS: Liver total, lean, and fat volumes were measured before and after (i) a
      6-day low-carbohydrate diet (n = 17), (ii) a 7-month standard hypocaloric diet (n
      = 26), and (iii) a 3-week high-carbohydrate diet (n = 17), by combining magnetic
      resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1) H-MRS)
      techniques. RESULTS: At baseline, three groups were comparable with respect to
      age, body mass index, liver volumes and the liver fat content. Body weight
      decreased similarly by the short-term and long-term hypocaloric diets. Liver
      total volume decreased significantly more during the short-term low-carbohydrate
      (-22 +/- 2%) than the long-term (-7 +/- 2%) hypocaloric diet (P < 0.001). This
      was due to a greater decrease in liver lean volume in the short-term (-20 +/- 2%)
      than the long-term (-4 +/- 2%) weight loss group (P < 0.001). Decreases in liver
      fat were comparable. Liver volume increased by 9 +/- 3% due to overfeeding (P<
      0.02 for before vs. after). CONCLUSIONS: These data support the use of a short
      term low-carbohydrate diet whenever a reduction in liver volume is desirable.
      Overeating carbohydrate is harmful because it increases liver volume.

PMID- 24115748
TI  - A review of the cultivation and processing of cannabis (Cannabis sativa L.) for
      production of prescription medicines in the UK.
AB  - The quality demands of the pharmaceutical industry require prescription medicines
      to be consistent in their active ingredient content. Achieving this, using raw
      cannabis as a feedstock, is especially challenging. The plant material is
      extremely inhomogeneous, and the ratios of active ingredients are affected by a
      range of factors. These include the genetics of the plant, the growing and
      storage conditions, the state of maturity at harvest, and the methods used to
      process and formulate the material. The reasons for this variability are
      described, with particular emphasis on the botanical considerations. To produce
      the complex botanical medicine Sativex(r), which contains the cannabinoids
      Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) and a range of other
      ingredients, GW Pharmaceuticals had to manage these variables. This medicine, for
      the treatment of spasticity due to multiple sclerosis, is the first cannabis
      based medicine to be approved in the UK. The company's methodology for producing
      this and other chemotypes is described.

PMID- 24115749
TI  - Drug-induced perturbations of the bile acid pool, cholestasis, and
      hepatotoxicity: mechanistic considerations beyond the direct inhibition of the
      bile salt export pump.
AB  - The bile salt export pump (BSEP) is located on the canalicular plasma membrane of
      hepatocytes and plays an important role in the biliary clearance of bile acids
      (BAs). Therefore, any drug or new chemical entity that inhibits BSEP has the
      potential to cause cholestasis and possibly liver injury. In reality, however,
      one must consider the complexity of the BA pool, BA enterohepatic recirculation
      (EHR), extrahepatic (renal) BA clearance, and the interplay of multiple
      participant transporters and enzymes (e.g., sulfotransferase 2A1, multidrug
      resistance-associated protein 2, 3, and 4). Moreover, BAs undergo extensive
      enzyme-catalyzed amidation and are subjected to metabolism by enterobacteria
      during EHR. Expression of the various enzymes and transporters described above is
      governed by nuclear hormone receptors (NHRs) that mount an adaptive response when
      intracellular levels of BAs are increased. The intracellular trafficking of
      transporters, and their ability to mediate the vectorial transport of BAs, is
      governed by specific kinases also. Finally, bile flow, micelle formation,
      canalicular membrane integrity, and BA clearance can be influenced by the
      inhibition of multidrug resistant protein 3- or ATPase-aminophospholipid
      transporter-mediated phospholipid flux. Consequently, when screening compounds in
      a discovery setting or conducting mechanistic studies to address clinical
      findings, one has to consider the direct (inhibitory) effect of the parent drug
      and metabolites on multiple BA transporters, as well as inhibition of BA
      sulfation and amidation and NHR function. Vectorial BA transport, in addition to
      BA EHR and homoeostasis, could also be impacted by drug-dependent modulation of
      kinases and enterobacteria. 

PMID- 24115750
TI  - Oatp1a1 requires PDZK1 to traffic to the plasma membrane by selective recruitment
      of microtubule-based motor proteins.
AB  - Previous studies identified a family of organic anion transport proteins (OATPs),
      many of which have C-terminal PDZ binding consensus sequences. In particular, the
      C-terminal four amino acids of Oatp1a1, a transporter on rat and mouse
      hepatocytes, comprise a consensus binding site for PDZK1. In PDZK1 knockout mice
      and in transfected cells where PDZK1 expression was knocked down, Oatp1a1
      accumulates in intracellular vesicles. The present study tests the hypothesis
      that Oatp1a1 traffics to and from the cell surface in vesicles along
      microtubules, and that PDZK1 guides recruitment of specific motors to these
      vesicles. Oatp1a1-containing vesicles were prepared from wild-type and PDZK1
      knockout mice. As seen by immunofluorescence, kinesin-1, a microtubule plus-end
      directed motor, was largely associated with vesicles from wild-type mouse liver,
      whereas dynein, a minus-end directed motor, was largely associated with vesicles
      from PDZK1 knockout mouse liver. Quantification of motility on directionally
      marked microtubules following addition of 50 uM ATP showed that wild-type
      vesicles moved equally toward the plus and minus ends whereas PDZK1 knockout
      vesicles moved predominantly toward the minus end, consistent with net movement
      toward the cell interior. These studies provide a novel mechanism by which PDZK1
      regulates intracellular trafficking of Oatp1a1 by recruiting specific motors to
      Oatp1a1-containing vesicles. In the absence of PDZK1, Oatp1a1-containing vesicles
      cannot recruit kinesin-1 and associate with dynein as a predominant minus-end
      directed motor. Whether this is a result of direct interaction of the Oatp1a1
      cytoplasmic domain with dynein or with a dynein-containing protein complex
      remains to be established. 

PMID- 24115752
TI  - Real-time optical detection of stabilized artificial G-quadruplexes under
      confined conditions.

PMID- 24115751
TI  - A role for cytochrome b5 in the In vivo disposition of anticancer and cytochrome
      P450 probe drugs in mice.
AB  - The role of microsomal cytochrome b5 (Cyb5) in defining the rate of drug
      metabolism and disposition has been intensely debated for several decades.
      Recently we described mouse models involving the hepatic or global deletion of
      Cyb5, demonstrating its central role in in vivo drug disposition. We have now
      used the cytochrome b5 complete null (BCN) model to determine the role of Cyb5 in
      the metabolism of ten pharmaceuticals metabolized by a range of cytochrome P450s,
      including five anticancer drugs, in vivo and in vitro. The extent to which
      metabolism was significantly affected by the absence of Cyb5 was substrate
      dependent; AUC increased (75-245%) and clearance decreased (35-72%) for
      phenacetin, metoprolol, and chlorzoxazone. Tolbutamide disposition was not
      significantly altered by Cyb5 deletion, while for midazolam clearance was
      decreased by 66%. The absence of Cyb5 had no effect on gefitinib and paclitaxel
      disposition, while significant changes in the in vivo pharmacokinetics were
      measured for: cyclophosphamide [maximum plasma concentration (Cmax) and terminal
      half-life increased 55% and 40%, respectively], tamoxifen (AUClast and Cmax
      increased 370% and 233%, respectively), and anastrozole (AUC and terminal half
      life increased 125% and 62%, respectively; clearance down 80%). These data
      provide strong evidence that both hepatic and extrahepatic Cyb5 levels are an
      important determinant of in vivo drug disposition catalyzed by a range of
      cytochrome P450s, including currently prescribed anticancer agents, and that
      individuality in Cyb5 expression could be a significant determinant in rates of
      drug disposition in man. 

PMID- 24115755
TI  - Prospects and limitations of "Click-Chemistry"-based DNA labeling technique
      employing 5-ethynyl-2'deoxyuridine (EdU).

PMID- 24115756
TI  - Ultrasound detection of cartilage calcification at knee level in calcium
      pyrophosphate deposition disease.
AB  - OBJECTIVE: To determine the sensitivity, specificity, and accuracy of ultrasound
      (US) in the detection of cartilage calcification at knee level in patients with
      calcium pyrophosphate deposition disease (CPDD) and to assess the interobserver
      reliability. METHODS: Seventy-four CPDD patients and 83 controls with other
      chronic arthritis were included. All patients underwent a clinical examination,
      synovial fluid analysis, and radiographic assessment of the knee. US examinations
      were performed in order to detect hyperechoic spots within the hyaline cartilage
      layer and hyperechoic areas within the meniscal fibrocartilage. Twenty patients
      were assessed by 2 operators in order to calculate the interobserver reliability.
      RESULTS: A total of 314 knees in 157 patients (74 with CPDD, 19 with rheumatoid
      arthritis, 17 with spondyloarthritis, 32 with osteoarthritis, and 15 with gout)
      were assessed. In the 74 patients with CPDD, hyaline cartilage spots were
      detected by US in at least 1 knee in 44 patients (59.5%), whereas radiography
      detected hyaline cartilage spots in 34 patients (45.9%) (P < 0.001). Meniscal
      fibrocartilage calcifications were detected by US in 67 of the 74 CPDD patients
      (90.5%), whereas conventional radiography detected calcifications in 62 patients
      (83.7%) (P = 0.011). The criterion validity expressed as percentage of
      sensitivity, specificity, and accuracy of US in the detection of articular
      cartilage calcification was high. Both kappa values and overall agreement
      percentages showed moderate to excellent agreement. CONCLUSION: US is an accurate
      and reliable imaging technique in the detection of articular cartilage
      calcification at knee level in patients with CPDD.

PMID- 24115757
TI  - Epicardial fat thickness and nonalcoholic fatty liver disease in obese subjects.
AB  - OBJECTIVE: Ectopic fat accumulation within the heart and the liver are linked to
      an increased cardiovascular risk. Ultrasound-measured cardiac and liver steatosis
      are easily accessible markers of intra-organ ectopic fat accumulation. The
      hypothesis that echocardiographic epicardial fat thickness is independently
      associated with nonalcoholic fatty liver disease (NAFLD) in obese subjects is
      tested. DESIGN AND METHODS: Sixty-two obese (BMI > 30 kg m-2) subjects with
      ultrasonographic evidence of NAFLD and 62 control obese subjects without history
      or signs of NAFLD underwent echocardiographic epicardial fat thickness
      measurement. RESULTS: Epicardial fat thickness was significantly higher (P <
      0.01) in obese subjects with NAFLD when compared to those without NAFLD.
      Epicardial fat thickness was significantly higher (9.7 +/- 0.2 vs. 8 +/- 0.7 mm,
      P < 0.01) in subjects with severe (ultrasound score 3) than those with moderate
      (score 2) liver steatosis. Among waist circumference and BMI, epicardial fat
      thickness resulted in the best independent correlate of liver steatosis (R2  =
      0.77, P < 0.001). CONCLUSIONS: Our study suggests that epicardial fat is a good
      predictor of liver steatosis in obese subjects. Echocardiographic epicardial fat
      predicts ultrasound-measured fatty liver better than BMI or waist circumferences
      does. Patients with severe fatty liver infiltration presented with the highest
      amount of cardiac fat accumulation.

PMID- 24115758
TI  - Enantiomeric separations of illicit drugs and controlled substances using
      cyclofructan-based (LARIHC) and cyclobond I 2000 RSP HPLC chiral stationary
      phases.
AB  - Recently a novel class of chiral stationary phases (CSPs) based on cyclofructan
      (CF) has been developed. Cyclofructans are cyclic oligosaccharides that possess a
      crown ether core and pendent fructofuranose moieties. Herein, we evaluate the
      applicability of these novel CSPs for the enantiomeric separation of chiral
      illicit drugs and controlled substances directly without any derivatization. A
      set of 20 racemic compounds were used to evaluate these columns including 8
      primary amines, 5 secondary amines, and 7 tertiary amines. Of the new
      cyclofructan-based LARIHC columns, 14 enantiomeric separations were obtained
      including 7 baseline and 7 partial separations. The LARIHC CF6-P column proved to
      be the most useful in separating illicit drugs and controlled substances
      accounting for 11 of the 14 optimized separations. The polar organic mode
      containing small amounts of methanol in acetonitrile was the most useful solvent
      system for the LARIHC CF6-P CSP. Furthermore, the LARIHC CF7-DMP CSP proved to be
      valuable for the separation of the tested chiral drugs resulting in four of the
      optimized enantiomeric separations, whereas the CF6-RN did not yield any optimum
      separations. The broad selectivity of the LARIHC CF7-DMP CSP is evident as it
      separated primary, secondary and tertiary amine containing chiral drugs. The
      compounds that were partially or un-separated using the cyclofructan based
      columns were screened with a Cyclobond I 2000 RSP column. This CSP provided three
      baseline and six partial separations.

PMID- 24115759
TI  - Refining similarity scoring to enable decoy-free validation in spectral library
      searching.
AB  - Spectral library searching is a maturing approach for peptide identification from
      MS/MS, offering an alternative to traditional sequence database searching.
      Spectral library searching relies on direct spectrum-to-spectrum matching between
      the query data and the spectral library, which affords better discrimination of
      true and false matches, leading to improved sensitivity. However, due to the
      inherent diversity of the peak location and intensity profiles of real spectra,
      the resulting similarity score distributions often take on unpredictable shapes.
      This makes it difficult to model the scores of the false matches accurately,
      necessitating the use of decoy searching to sample the score distribution of the
      false matches. Here, we refined the similarity scoring in spectral library
      searching to enable the validation of spectral search results without the use of
      decoys. We rank-transformed the peak intensities to standardize all spectra,
      making it possible to fit a parametric distribution to the scores of the nontop
      scoring spectral matches. The statistical significance of the top-scoring match
      can then be estimated in a rigorous manner according to Extreme Value Theory. The
      overall result is a more robust and interpretable measure of the quality of the
      spectral match, which can be obtained without decoys. We tested this refined
      similarity scoring function on real datasets and demonstrated its effectiveness.
      This approach reduces search time, increases sensitivity, and extends spectral
      library searching to situations where decoy spectra cannot be readily generated,
      such as in searching unidentified and nonpeptide spectral libraries.

PMID- 24115760
TI  - Field-free, sheathless cell focusing in exponentially expanding hydrophoretic
      channels for microflow cytometry.
AB  - Cell focusing into a narrow stream is an essential step prior to counting and
      sorting cells in microfluidic devices for flow cytometry and cell sorting
      applications. Hydrodynamic focusing techniques, however, rely on the need for
      large volumes of sheath liquid and complex mechanical setup for flow control,
      preventing miniaturization of the systems. Although microfluidic methods based on
      active or passive particle control offer sheathless and efficient focusing, they
      often accompany fabrication complexities or bulky external setups, and operate in
      a certain range of flow rates. We present here a microfluidic device to focus
      cells into a narrow stream. The device employs hydrophoresis to guide cells by
      locally patterned slanted grooves, and channel expansion to improve focusing
      efficiency and produce a narrow stream of cells. This device principle allows
      easy improvement of focusing efficiency by adding more expansion steps. Adjusting
      channel expansion also ensures successful cell focusing without defocusing by
      inertial effects even at high Reynolds numbers. Using this device, we
      successfully produced a narrow stream of cells having size variation of >11% in a
      coefficient of variation (CV), achieving a narrow cell stream with a focusing
      variation below CV of 3.0%.

PMID- 24115761
TI  - Taking charge of systemic sclerosis: a pilot study to assess the effectiveness of
      an internet self-management program.
AB  - OBJECTIVE: To assess the effects of an internet self-management program for
      systemic sclerosis on self-efficacy, health efficacy, and management of care,
      pain, fatigue, functional ability, and depression. METHODS: Participants logged
      on to a password-protected web site and completed modules and learning activities
      at their own pace over 10 weeks. Participants were encouraged to log on to the
      discussion board, participate in an interactive component of the web site, and
      respond to questions posted for each module. Participants completed pre- and
      postintervention questionnaires on perceived self-efficacy, health efficacy,
      ability to manage care, functional disability,depression, pain, and fatigue. They
      also completed an 8-question evaluation form regarding satisfaction with the web
      site, program content, discussion boards, and learning activities. RESULTS:
      Sixteen participants completed the study and postintervention measures. There
      were significant improvements in mean scores for ability to manage care (effect
      size [ES] 0.62, P = 0.025) and health efficacy (ES 0.72, P = 0.012), and
      significant decreases in fatigue (ES 0.55, P = 0.045) and depression (ES 0.71, P
      = 0.013). Self-efficacy improved, but not significantly. The evaluation of the
      program revealed mean scores ranging from 4.2 (web site was visually appealing)
      to 4.9 (information presented clearly) on a 5-point scale, where 5 is most
      satisfied. CONCLUSION: These findings from this pilot study suggest that a self
      management program delivered using an internet format can lead to statistically
      significant changes in health efficacy and management of care, fatigue, and
      depression. These results need to be confirmed with a larger randomized
      controlled trial with a longer followup period.

PMID- 24115762
TI  - Classification tree analyses reveal limited potential for early targeted
      prevention against childhood overweight.
AB  - OBJECTIVE: Whether specific combinations of risk factors in very early life might
      allow identification of high-risk target groups for overweight prevention
      programs was examined. DESIGN AND METHODS: Data of n = 8981 children from the
      German KiGGS study were analyzed. Using a classification tree approach,
      predictive risk factor combinations were assessed for overweight in 3-6, 7-10,
      and 11-17-year-old children. RESULTS: In preschool children, the subgroup with
      the highest overweight risk were migrant children with at least one obese parent,
      with a prevalence of 36.6 (95% confidence interval or CI: 22.9, 50.4)%, compared
      to an overall prevalence of 10.0 (8.9, 11.2)%. The prevalence of overweight
      increased from 18.3 (16.8, 19.8)% to 57.9 (46.6, 69.3)% in 7-10-year-old
      children, if at least one parent was obese and the child had been born large-for
      gestational-age. In 11-17-year-olds, the overweight risk increased from 20.1
      (18.9, 21.3)% to 63.0 (46.4, 79.7)% in the highest risk group. However, high
      prevalence ratios were found only in small subgroups, containing <10% of all
      overweight cases in the respective age group. CONCLUSIONS: Our results indicate
      only a limited potential for early targeted preventions against overweight in
      children and adolescents.

PMID- 24115763
TI  - Altitude exposure in sports: the Athlete Biological Passport standpoint.
AB  - The Athlete Biological Passport (ABP) is principally founded on monitoring an
      athlete's biological variables over time, to identify abnormal biases on a
      longitudinal basis. Several factors are known to influence the results of these
      markers. However, the manner in which the altitude factor is taken into account
      still needs to be standardized. Causal relationships between haematological
      variables should be correctly integrated into ABP software. In particular,
      modifications of haematological parameters during and after exposure to different
      altitudes/hypoxic protocols need to be properly included within detection models.

PMID- 24115764
TI  - Impairment of dynamic single-leg balance performance in individuals with hip
      chondropathy.
AB  - OBJECTIVE: Impaired balance control has been reported in the elderly with hip
      osteoarthritis, yet this relationship has not been explored in young adults with
      hip chondropathy. This study aimed to determine whether people with hip
      chondropathy demonstrated impaired balance ability during a dynamic single-leg
      squat with eyes open (SquatEO) and a single-leg standing task with eyes closed
      (StandEC) and whether hip range of motion (ROM) and hip muscle strength were
      correlated with balance measures in adults with hip chondropathy. METHODS: Sixty
      three adults with hip chondropathy and 60 controls performed 2 tasks: SquatEO and
      StandEC while standing on a Nintendo Wii Balance Board. Center of pressure (COP)
      movement in mediolateral and anteroposterior directions was extracted. Hip ROM
      and muscle strength were measured with an inclinometer and dynamometer. Data were
      analyzed using an analysis of covariance and stepwise multiple regression model.
      RESULTS: During SquatEO, greater COP mediolateral range (P = 0.023) and
      anteroposterior SD (P = 0.043) were observed in those with hip chondropathy
      compared to controls. No significant between-group differences were observed for
      StandEC. Hip external rotation ROM was significantly associated with mediolateral
      range during SquatEO. CONCLUSION: Dynamic single-leg balance squat performance is
      reduced in people with hip chondropathy compared to healthy adults, but static
      single-leg standing balance is not. This may be reflective of reduced control of
      dynamic movements. Those with greater hip joint external rotation ROM appear to
      have worse single-leg squat balance performance. Further investigation into
      balance deficits associated with hip disease is necessary to establish early
      identification strategies and a tailored approach to rehabilitation.

PMID- 24115765
TI  - A comparison of functional brain changes associated with surgical versus
      behavioral weight loss.
AB  - OBJECTIVE: Few studies have examined brain changes in response to effective
      weight loss; none have compared different methods of weight-loss intervention.
      Functional brain changes associated with a behavioral weight loss intervention to
      those associated with bariatric surgery were compared. DESIGN AND METHODS:
      Fifteen obese participants were recruited prior to adjustable gastric banding
      surgery and 16 obese participants were recruited prior to a behavioral diet
      intervention. Groups were matched for demographics and amount of weight lost.
      Functional magnetic resonance imaging scans (visual food motivation paradigm
      while hungry and following a meal) were conducted before and 12 weeks after
      surgery/behavioral intervention. RESULTS: When compared to bariatric patients in
      the premeal analyses, behavioral dieters showed increased activation to food
      images in right medial prefrontal cortex (PFC) and left precuneus following
      weight loss. When compared to behavioral dieters, bariatric patients showed
      increased activation in bilateral temporal cortex following weight loss.
      CONCLUSIONS: Behavioral dieters showed increased responses to food cues in medial
      PFC-a region associated with valuation and processing of self-referent
      information-when compared to bariatric patients. Bariatric patients showed
      increased responses to food cues in brain regions associated with higher level
      perception-when compared to behavioral dieters. The method of weight loss
      determines unique changes in brain function.

PMID- 24115766
TI  - Exploiting the bad eating habits of Ras-driven cancers.
AB  - Oncogenic Ras promotes glucose fermentation and glutamine use to supply central
      carbon metabolism, but how and why have only emerged recently. Ras-mediated
      metabolic reprogramming generates building blocks for growth and promotes
      antioxidant defense. To fuel metabolic pathways, Ras scavenges extracellular
      proteins and lipids. To bolster metabolism and mitigate stress, Ras activates
      cellular self-cannibalization and recycling of proteins and organelles by
      autophagy. Targeting these distinct features of Ras-driven cancers provides novel
      approaches to cancer therapy. 

PMID- 24115768
TI  - Molecular basis of telomere syndrome caused by CTC1 mutations.
AB  - Mutations in CTC1 lead to the telomere syndromes Coats Plus and dyskeratosis
      congenita (DC), but the molecular mechanisms involved remain unknown. CTC1 forms
      with STN1 and TEN1 a trimeric complex termed CST, which binds ssDNA, promotes
      telomere DNA synthesis, and inhibits telomerase-mediated telomere elongation.
      Here we identify CTC1 disease mutations that disrupt CST complex formation, the
      physical interaction with DNA polymerase alpha-primase (polalpha-primase),
      telomeric ssDNA binding in vitro, accumulation in the nucleus, and/or telomere
      association in vivo. While having diverse molecular defects, CTC1 mutations
      commonly lead to the accumulation of internal single-stranded gaps of telomeric
      DNA, suggesting telomere DNA replication defects as a primary cause of the
      disease. Strikingly, mutations in CTC1 may also unleash telomerase repression and
      telomere length control. Hence, the telomere defect initiated by CTC1 mutations
      is distinct from the telomerase insufficiencies seen in classical forms of
      telomere syndromes, which cause short telomeres due to reduced maintenance of
      distal telomeric ends by telomerase. Our analysis provides molecular evidence
      that CST collaborates with DNA polalpha-primase to promote faithful telomere DNA
      replication. 

PMID- 24115767
TI  - Calorie restriction and sirtuins revisited.
AB  - Calorie or dietary restriction (CR) has attracted attention because it is the
      oldest and most robust way to extend rodent life span. The idea that the nutrient
      sensors, termed sirtuins, might mediate effects of CR was proposed 13 years ago
      and has been challenged in the intervening years. This review addresses these
      challenges and draws from a great body of new data in the sirtuin field that
      shows a systematic redirection of mammalian physiology in response to diet by
      sirtuins. The prospects for drugs that can deliver at least a subset of the
      benefits of CR seems very real. 

PMID- 24115769
TI  - The SMG5-SMG7 heterodimer directly recruits the CCR4-NOT deadenylase complex to
      mRNAs containing nonsense codons via interaction with POP2.
AB  - Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality control mechanism that
      detects aberrant mRNAs containing nonsense codons and induces their rapid
      degradation. This degradation is mediated by SMG6, an NMD-specific endonuclease,
      as well as the SMG5 and SMG7 proteins, which recruit general mRNA decay enzymes.
      However, it remains unknown which specific decay factors are recruited and
      whether this recruitment is direct. Here, we show that SMG7 binds directly to
      POP2, a catalytic subunit of the CCR4-NOT deadenylase complex, and elicits
      deadenylation-dependent decapping and 5'-to-3' decay of NMD targets. Accordingly,
      a catalytically inactive POP2 mutant partially suppresses NMD in human cells. The
      SMG7-POP2 interaction is critical for NMD in cells depleted of SMG6, indicating
      that SMG7 and SMG6 act redundantly to promote the degradation of NMD targets. We
      further show that UPF1 provides multiple binding sites for decapping factors.
      These data unveil a missing direct physical link between NMD and the general mRNA
      decay machinery and indicate that NMD employs diverse and partially redundant
      mechanisms to ensure robust degradation of aberrant mRNAs. 

PMID- 24115770
TI  - Dual mechanisms prevent premature chromosome segregation during meiosis.
AB  - In meiosis I, homologous chromosomes pair and then attach to the spindle so that
      the homologs can be pulled apart at anaphase I. The segregation of homologs
      before pairing would be catastrophic. We describe two mechanisms that prevent
      this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian
      Aurora B kinase, triggers shedding of a kinetochore protein, preventing
      microtubule attachment. Second, Ipl1 localizes to the spindle pole bodies (SPBs),
      where it blocks spindle assembly. These processes are reversed upon expression of
      Ndt80. Previous studies have shown that Ndt80 is expressed when homologs have
      successfully partnered, and this triggers a rise in the levels of cyclin
      dependent kinase (CDK). We found that CDK phosphorylates Ipl1, delocalizing it
      from SPBs, triggering spindle assembly. At the same time, kinetochores
      reassemble. Thus, dual mechanisms controlled by Ipl1 and Ntd80 coordinate
      chromosome and spindle behaviors to prevent the attachment of unpartnered
      chromosomes to the meiotic spindle. 

PMID- 24115771
TI  - A developmentally regulated translational control pathway establishes the meiotic
      chromosome segregation pattern.
AB  - Production of haploid gametes from diploid progenitor cells is mediated by a
      specialized cell division, meiosis, where two divisions, meiosis I and II, follow
      a single S phase. Errors in progression from meiosis I to meiosis II lead to
      aneuploid and polyploid gametes, but the regulatory mechanisms controlling this
      transition are poorly understood. Here, we demonstrate that the conserved kinase
      Ime2 regulates the timing and order of the meiotic divisions by controlling
      translation. Ime2 coordinates translational activation of a cluster of genes at
      the meiosis I-meiosis II transition, including the critical determinant of the
      meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates
      translational control through the meiosis-specific RNA-binding protein Rim4. Rim4
      inhibits translation of CLB3 during meiosis I by interacting with the 5'
      untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase
      activity rises and triggers a decrease in Rim4 protein levels, thereby
      alleviating translational repression. Our results elucidate a novel
      developmentally regulated translational control pathway that establishes the
      meiotic chromosome segregation pattern. 

PMID- 24115772
TI  - SIN-dependent phosphoinhibition of formin multimerization controls fission yeast
      cytokinesis.
AB  - Many eukaryotes accomplish cell division by building and constricting a medial
      actomyosin-based cytokinetic ring (CR). In Schizosaccharomyces pombe, a Hippo
      related signaling pathway termed the septation initiation network (SIN) controls
      CR formation, maintenance, and constriction. However, how the SIN regulates
      integral CR components was unknown. Here, we identify the essential cytokinetic
      formin Cdc12 as a key CR substrate of SIN kinase Sid2. Eliminating Sid2-mediated
      Cdc12 phosphorylation leads to persistent Cdc12 clustering, which prevents CR
      assembly in the absence of anillin-like Mid1 and causes CRs to collapse when
      cytokinesis is delayed. Molecularly, Sid2 phosphorylation of Cdc12 abrogates
      multimerization of a previously unrecognized Cdc12 domain that confers F-actin
      bundling activity. Taken together, our findings identify a SIN-triggered
      oligomeric switch that modulates cytokinetic formin function, revealing a novel
      mechanism of actin cytoskeleton regulation during cell division. 

PMID- 24115774
TI  - Biological age revisited.

PMID- 24115773
TI  - Cognitive aging and rate of hospitalization in an urban population of older
      people.
AB  - BACKGROUND: The association of age-related cognitive change with hospitalization
      is not well understood. METHODS: At 3-year intervals for a mean of 8.7 years,
      2,273 older residents of a geographically defined urban community underwent
      cognitive testing from which a global measure was derived. Hospitalization data
      were obtained from Part A Medicare beneficiary records. The association of level
      of cognitive function and rate of cognitive decline in each 3-year interval with
      subsequent rate of hospitalization was assessed using mixed-effects count
      regression models. RESULTS: There were 9,091 hospitalizations involving 1,810 of
      the 2,273 individuals in the cohort (79.6%). Rate of hospitalization increased by
      9.7% (95% confidence interval [CI]: 7.2, 12.3) with each additional study year;
      by 32.7% (95% CI: 26.8, 38.0) for each 1 point lower on the global cognitive
      measure at the beginning of an observation interval; and by 24.3% (95% CI: 16.6,
      32.6) for each 1-point decrease in the global cognitive measure during the
      previous observation period. These associations persisted after adjustment for
      comorbidities and exclusion of those with a Mini-Mental State Examination score
      less than 26. CONCLUSION: Individual differences in trajectories of cognitive
      aging are associated with subsequent risk of hospitalization.

PMID- 24115775
TI  - Response to Dr. Mitnitski's and Dr. Rockwood's letter to the editor: Biological
      age revisited.

PMID- 24115776
TI  - Aging, empathy, and prosociality.
AB  - OBJECTIVES: Although empathy is a well-established motivation in younger adults
      for helping others, it is not known whether this extends to aging. Prioritization
      of socioemotional goals with age may increase the salience of helping others
      (i.e., prosocial behavior), but older adults also experience decreased cognitive
      empathy. Thus, we investigated age-related differences in relationships among
      empathy and prosocial behavior. METHOD: Participants were 24 younger (M = 19.8
      years) and 24 older (M = 77.9 years) healthy adults. Whereas participants
      believed the study involved playing the dictator game, in reality, state
      emotional empathy was induced implicitly through a note from an opponent
      describing their experience with cancer. Prosocial behavior was measured by
      participants' monetary offers to that opponent. RESULTS: Older adults showed
      greater prosocial behavior due to the empathy induction than younger adults.
      There was a positive association between state emotional empathy ratings and
      prosocial behavior in older, but not in younger adults, and preliminary evidence
      for higher state emotional empathy levels in older adults with higher trait
      cognitive empathy. DISCUSSION: This suggests that in contexts relevant to
      socioemotional goals, older adults may be more motivated than younger adults to
      help others and state emotional empathy may be a potential mechanism for greater
      prosocial behavior in aging.

PMID- 24115777
TI  - Does the distribution of healthcare utilization match needs in Africa?
AB  - An equitable distribution of healthcare use, distributed according to people's
      needs instead of ability to pay, is an important goal featuring on many health
      policy agendas worldwide. However, relatively little is known about the extent to
      which this principle is violated across socio-economic groups in Sub-Saharan
      Africa (SSA). We examine cross-country comparative micro-data from 18 SSA
      countries and find that considerable inequalities in healthcare use exist and
      vary across countries. For almost all countries studied, healthcare utilization
      is considerably higher among the rich. When decomposing these inequalities we
      find that wealth is the single most important driver. In 12 of the 18 countries
      wealth is responsible for more than half of total inequality in the use of care,
      and in 8 countries wealth even explains more of the inequality than need,
      education, employment, marital status and urbanicity together. For the richer
      countries, notably Mauritius, Namibia, South Africa and Swaziland, the
      contribution of wealth is typically less important. As the bulk of inequality is
      not related to need for care and poor people use less care because they do not
      have the ability to pay, healthcare utilization in these countries is to a large
      extent unfairly distributed. The weak average relationship between need for and
      use of health care and the potential reporting heterogeneity in self-reported
      health across socio-economic groups imply that our findings are likely to even
      underestimate actual inequities in health care. At a macro level, we find that a
      better match of needs and use is realized in those countries with better
      governance and more physicians. Given the absence of social health insurance in
      most of these countries, policies that aim to reduce inequities in access to and
      use of health care must include an enhanced capacity of the poor to generate
      income. 

PMID- 24115779
TI  - Managing ambivalent prejudices: The smart-but-cold, and the warm-butdumb
      sterotypes.
AB  - Not all biases are equivalent, and not all biases are uniformly negative. Two
      fundamental dimensions differentiate stereotyped groups in cultures across the
      globe: status predicts perceived competence, and cooperation predicts perceived
      warmth. Crossing the competence and warmth dimensions, two combinations produce
      ambivalent prejudices: pitied groups (often traditional women or older people)
      appear warm but incompetent, and envied groups (often nontraditional women or
      outsider entrepreneurs) appear competent but cold. Case studies in ambivalent
      sexism, heterosexism, racism, anti-immigrant biases, ageism, and classism
      illustrate both the dynamics and the management of these complex but knowable
      prejudices.

PMID- 24115780
TI  - A Simulation Based Evaluation of the Asymptotic Power Formulae for Cox Models in
      Small Sample Cases.
AB  - Cox proportional hazards (PH) models are commonly used in medical research to
      investigate the associations between covariates and time to event outcomes. It is
      frequently noted that with less than ten events per covariate, these models
      produce spurious results, and therefore, should not be used. Statistical
      literature contains asymptotic power formulae for the Cox model which can be used
      to determine the number of events needed to detect an association. Here we
      investigate via simulations the performance of these formulae in small sample
      settings for Cox models with 1- or 2-covariates. Our simulations indicate that,
      when the number of events is small, the power estimate based on the asymptotic
      formulae is often inflated. The discrepancy between the asymptotic and empirical
      power is larger for the dichotomous covariate especially in cases where
      allocation of sample size to its levels is unequal. When more than one covariate
      is included in the same model, the discrepancy between the asymptotic power and
      the empirical power is even larger, especially when a high positive correlation
      exists between the two covariates.

PMID- 24115782
TI  - Taxonomic and molecular identification of hemicaloosia, hemicycliophora,
      gracilacus and paratylenchus species (nematoda: criconematidae).
AB  - Populations of Hemicycliophora epicharoides, H. gigas, H. labiata, H. pruni, H.
      shepherdi, H. vidua, H. zuckermani, Gracilacus straeleni, and Paratylenchus
      labiosus were obtained from different geographical areas in the continental
      United States and characterized morphological and molecularly. Two new species of
      Hemicycliophorinae: Hemicaloosia uarki n. sp from Pinetree, St. Francis County,
      Arkansas, and Hemicycliophora wyei n. sp from Wayne County, North Carolina, are
      also described. Hemicaloosia uarki n. sp. is characterized by having two lip
      annuli separated from the rest of body and directed anteriorly, a long stylet
      (106-124 MUm), long body length (1,081-1,326 MUm) and a single lateral fields
      demarcated by interruptions of the body annuli. Hemicycliophora wyei n. sp.
      showed a lateral fields demarked by two faint lines with transverse anastomoses
      and/or breaks of the striae; an elongated not offset conical tail with distinct
      annulations and a rounded tip and long vulval lips with a vulval sleeve. The
      molecular characterizations of the new (H. uarki n. sp. and H. wyei n. sp.) and
      known species of Criconematidae using the ITS1 rDNA gene sequence and the
      molecular phylogenetic relationships are provided. 

PMID- 24115781
TI  - Recent Progress in Photocatalysis Mediated by Colloidal II-VI Nanocrystals.
AB  - The use of photoexcited electrons and holes in semiconductor nanocrystals as
      reduction and oxidation reagents is an intriguing way of harvesting photon energy
      to drive chemical reactions. This review focuses on recent research efforts to
      understand and control the photocatalytic processes mediated by colloidal II-VI
      nanocrystalline materials, such as cadmium and zinc chalcogenides. First, we
      highlight how nanocrystal properties govern the rates and efficiencies of charge
      transfer processes relevant to photocatalysis. We then describe the use of
      nanocrystal catalyst heterostructures for fuel-forming reactions, most commonly
      H2 generation. Finally, we review the use of nanocrystal photocatalysis as a
      synthetic tool for metal-semiconductor nano-heterostructures.

PMID- 24115783
TI  - Two androdioecious and one dioecious new species of pristionchus (nematoda:
      diplogastridae): new reference points for the evolution of reproductive mode.
AB  - Rhabditid nematodes are one of a few animal taxa in which androdioecious
      reproduction, involving hermaphrodites and males, is found. In the genus
      Pristionchus, several cases of androdioecy are known, including the model species
      P. pacificus. A comprehensive understanding of the evolution of reproductive mode
      depends on dense taxon sampling and careful morphological and phylogenetic
      reconstruction. In this article, two new androdioecious species, P. boliviae n.
      sp. and P. mayeri n. sp., and one gonochoristic outgroup, P. atlanticus n. sp.,
      are described on morphological, molecular, and biological evidence. Their
      phylogenetic relationships are inferred from 26 ribosomal protein genes and a
      partial SSU rRNA gene. Based on current representation, the new androdioecious
      species are sister taxa, indicating either speciation from an androdioecious
      ancestor or rapid convergent evolution in closely related species. Male sexual
      characters distinguish the new species, and new characters for six closely
      related Pristionchus species are presented. Male papillae are unusually variable
      in P. boliviae n. sp. and P. mayeri n. sp., consistent with the predictions of
      "selfing syndrome." Description and phylogeny of new androdioecious species,
      supported by fuller outgroup representation, establish new reference points for
      mechanistic studies in the Pristionchus system by expanding its comparative
      context. 

PMID- 24115784
TI  - Host Status of Different Potato (Solanum tuberosum) Varieties and Hatching in
      Root Diffusates of Globodera ellingtonae.
AB  - Globodera ellingtonae was detected in Oregon in 2008. In order to make decisions
      regarding the regulation of this nematode, knowledge of its biology is required.
      We determined the host status of a diversity of potato (Solanum tuberosum)
      varieties in soil-based experiments and identified hatching stimulants in in
      vitro hatching assays. 'Russet Burbank,' 'Desiree,' 'Modac,' 'Norland,'
      'Umatilla,' and 'Yukon Gold' were good hosts (RF > 14) for G. ellingtonae. Potato
      varieties 'Maris Piper,' 'Atlantic,' and 'Satina,' all which contain the Ro1 gene
      that confers resistance to G. rostochiensis, were not hosts for G. ellingtonae.
      In in vitro hatching assays, G. ellingtonae hatched readily in the presence of
      diffusates from potato (PRD) and tomato (Solanum lycopersicum; TRD). Egg hatch
      occurred in an average of between 87% and 90% of exposed cysts, with an average
      of between 144 and 164 juveniles emerging per cyst, from PRD- and TRD-treated
      cysts, respectively. This nematode hatched rapidly in the presence of PRD and
      TRD, with at least 66% of total hatch occurring by day 3 of exposure. There was
      no dose-response of egg hatch to concentrations of PRD or TRD ranging from 1:5 to
      1:100 diffusate to water. When G. ellingtonae was exposed to root diffusates from
      21 different plants, hatch occurred in 0% to 70% of exposed cysts, with an
      average of between 0 to 27 juveniles emerging per cyst. When root diffusate
      exposed cysts were subsequently transferred to PRD to test viability, root
      diffusates from arugula (Eruca sativa), sudangrass (Sorghum bicolor subsp.
      drummondii), and common vetch (Vicia sativa) continued to inhibit egg hatch
      compared with the other root diffusates or water in which hatch occurred readily
      (60 to 182 juveniles emerging per cyst). Previously known hatching stimulants of
      G. rostochiensis and G. pallida, sodium metavanadate, sodium orthovanadate, and
      sodium thiocyanate, stimulated some egg hatch. Although, Globodera ellingtonae
      hatched readily in PRD and TRD and reproduced on potato, the pathogenicity of
      this nematode on potato remains to be determined. 

PMID- 24115785
TI  - Site-Specific Management of Meloidogyne chitwoodi in Idaho Potatoes Using 1,3
      Dichloropropene; Approach, Experiences, and Economics.
AB  - Fumigation for nematode management in irrigated potato production systems of
      Idaho is widely practiced. Soil injection is the only labeled application method
      for 1,3-dichloropropene that is conventionally applied on a whole-field basis.
      Plant-parasitic nematode species exhibit spatially variable population densities
      that provide an opportunity to practice site-specific fumigation to reduce
      chemical usage and production costs. During 2002 to 2008, 62 fields intended for
      commercial potato production in eastern Idaho were sampled using a geo-referenced
      grid sampling system for plant-parasitic nematode population densities. In total,
      4,030 grid samples were collected representing nearly 3,200 ha of commercial
      potato production. Collectively, 73% of the grid samples had Columbia root knot
      (CRN) (Meloidogyne chitwoodi) population densities below detectable levels. Site
      specific fumigation is the practice of varying application rate of a fumigant
      based on nematode population density. In 2007, 640 ha of potato production were
      site-specific fumigated for CRN nematode control in eastern Idaho. On average,
      this practice resulted in a 30% reduction in chemical usage and production cost
      savings of $209/ha when 1,3-dichloropropene was used as the sole source of
      nematode suppression. Reductions in usage of 1,3-dichloropropene can exceed 50%
      if used in combination with a nonfumigant nematicide such as oxamyl. This
      combination approach can have production cost savings exceeding $200/ha. Based on
      farm-gate receipts and USDA inspections provided by potato producers from 2001 to
      2011, potato tuber yield and quality have not been adversely affected using site
      specific fumigation. 

PMID- 24115786
TI  - Nematode Genera in Forest Soil Respond Differentially to Elevated CO2.
AB  - Previous reports suggest that fungivorous nematodes are the only trophic group in
      forest soils affected by elevated CO2. However, there can be ambiguity within
      trophic groups, and we examined data at a genus level to determine whether the
      conclusion remains similar. Nematodes were extracted from roots and soil of
      loblolly pine (Pinus taeda) and sweet gum (Liquidambar styraciflua) forests
      fumigated with either ambient air or CO2-enriched air. Root length and nematode
      biomass were estimated using video image analysis. Most common genera included
      Acrobeloides, Aphelenchoides, Cephalobus, Ditylenchus, Ecphyadorphora, Filenchus,
      Plectus, Prismatolaimus, and Tylencholaimus. Maturity Index values and diversity
      increased with elevated CO2 in loblolly pine but decreased with elevated CO2 in
      sweet gum forests. Elevated CO2 treatment affected the occurrence of more
      nematode genera in sweet gum than loblolly pine forests. Numbers were similar but
      size of Xiphinema decreased in elevated CO2. Abundance, but not biomass, of
      Aphelenchoides was reduced by elevated CO2. Treatment effects were apparent at
      the genus levels that were masked at the trophic level. For example, bacterivores
      were unaffected by elevated CO2, but abundance of Cephalobus was affected by CO2
      treatment in both forests. 

PMID- 24115787
TI  - Effects of a Commercial Formulation of Paecilomyces lilacinus Strain 251 on
      Overseeded Bermudagrass Infested with Belonolaimus longicaudatus.
AB  - Belonolaimus longicaudatus is an important parasite of both warm-season
      bermudagrass and winter overseed grasses used on golf courses in the southeastern
      United States. Field trials were conducted to study the effects of a commercial
      formulation of Paecilomyces lilacinus strain 251 applied to overseed grasses
      during the winter and early spring on population density of B. longicaudatus and
      bermudagrass health in late spring after bermudagrass broke dormancy. These
      studies found that P. lilacinus reduced numbers of B. longicaudatus in most
      cases, but not below damaging levels. Multiple applications of 1 * 10(10)
      spores/m(2) were generally more effective than 2 * 10(10) spores/m(2) in reducing
      nematode numbers and improving turf roots. These results indicate that
      application of this formulation of P. lilacinus strain 251 to overseeded turf in
      the spring may be a useful integrated pest management tool for B. longicaudatus
      on bermudagrass, but is not sufficient as a stand-alone nematode management
      tactic. 

PMID- 24115788
TI  - Effect of Soybean Monoculture on the Bacterial Communities Associated with Cysts
      of Heterodera glycines.
AB  - The soybean cyst nematode (SCN), Heterodera glycines, can cause significant
      reductions in soybean yield and quality in many parts of the world. Natural
      biological control may play an important role in regulating SCN population. In
      this study the bacterial communities associated with SCN cysts obtained from
      fields under different lengths of soybean monoculture were explored. Soil samples
      were collected in 2010 and 2011 from six fields that had been used for soybean
      monoculture for 2 to 41 yr. SCN population densities were determined and
      bacterial communities from SCN cysts were investigated by Biolog and PCR-DGGE
      methods. SCN population densities initially increased in the first 5 yr of
      soybean monoculture but then declined steeply as years of soybean monoculture
      increased. Catabolic diversity of bacterial communities associated with cysts
      tended to decline as number of years of monoculture increased. Some specific PCR
      DGGE bands, mainly representing Streptomyces and Rhizobium, were obtained from
      the cysts collected from the long-term monoculture fields. Principal component
      analysis of Biolog and PCR-DGGE data revealed that bacterial communities
      associated with cysts could be divided into two groups: those from cysts obtained
      from shorter (< 8 yr) vs. longer (> 8 yr) monoculture. This research demonstrates
      that the composition of the bacterial communities obtained from SCN cysts changes
      with length of soybean monoculture; the suppressive impact of these bacterial
      communities to SCN is yet to be determined. 

PMID- 24115791
TI  - Elimination of sleeping sickness hindered by difficult diagnosis.

PMID- 24115792
TI  - Health rights in the post-2015 development agenda: including non-nationals.

PMID- 24115794
TI  - Russian city offers health pursuits for all ages.

PMID- 24115795
TI  - Giving hope to rural women with obstetric fistula in Ethiopia.

PMID- 24115796
TI  - Variations in catastrophic health expenditure estimates from household surveys in
      India.
AB  - OBJECTIVE: To assess the comparability of out-of-pocket (OOP) payment and
      catastrophic health expenditure (CHE) estimates from different household surveys
      in India. METHODS: Data on CHE, outpatient and inpatient OOP payments and other
      expenditure from all major national or multi-state surveys since 2000 were
      compared. These included two consumer expenditure surveys (the National Sample
      Survey for 2004-05 [NSS 2004-05] and 2009-10 [NSS 2009-10]) and three health
      focused surveys (the World Health Survey 2003 [WHS 2003]; the National Sample
      Survey on Morbidity, Health Care and the Condition of the Aged 2004 [NSS 2004];
      and the Study on Global Ageing and Adult Health 2007-08 [SAGE 2007-08]). All but
      the NSS 2004-05 and the NSS 2009-10 used different questionnaires. FINDINGS: CHE
      estimates from WHS 2003 and SAGE 2007-08 were twice as high as those from NSS
      2004-05, NSS 2009-10 and NSS 2004. Inpatient OOP payment estimates were twice as
      high in WHS 2003 and SAGE 2007-08 because in these surveys a much higher
      proportion of households reported such payments. However, estimates of
      expenditures on other items were half as high in WHS 2003 as in the other surveys
      because a very small number of items was used to capture these expenditures.
      CONCLUSION: The wide variations observed in CHE and OOP payment estimates
      resulted from methodological differences. Survey methods used to assess CHE in
      India need to be standardized and validated to accurately track CHE and assess
      the impact of recent policies to reduce it.

PMID- 24115797
TI  - Economic evaluation of neonatal care packages in a cluster-randomized controlled
      trial in Sylhet, Bangladesh.
AB  - OBJECTIVE: To evaluate and compare the cost-effectiveness of two strategies for
      neonatal care in Sylhet division, Bangladesh. METHODS: In a cluster-randomized
      controlled trial, two strategies for neonatal care--known as home care and
      community care--were compared with existing services. For each study arm,
      economic costs were estimated from a societal perspective, inclusive of programme
      costs, provider costs and household out-of-pocket payments on care-seeking.
      Neonatal mortality in each study arm was determined through household surveys.
      The incremental cost-effectiveness of each strategy--compared with that of the
      pre-existing levels of maternal and neonatal care--was then estimated. The levels
      of uncertainty in our estimates were quantified through probabilistic sensitivity
      analysis. FINDINGS: The incremental programme costs of implementing the home-care
      package were 2939 (95% confidence interval, CI: 1833-7616) United States dollars
      (US$) per neonatal death averted and US$ 103.49 (95% CI: 64.72-265.93) per
      disability-adjusted life year (DALY) averted. The corresponding total societal
      costs were US$ 2971 (95% CI: 1844-7628) and US$ 104.62 (95% CI: 65.15-266.60),
      respectively. The home-care package was cost-effective--with 95% certainty--if
      healthy life years were valued above US$ 214 per DALY averted. In contrast,
      implementation of the community-care strategy led to no reduction in neonatal
      mortality and did not appear to be cost-effective. CONCLUSION: The home-care
      package represents a highly cost-effective intervention strategy that should be
      considered for replication and scale-up in Bangladesh and similar settings
      elsewhere.

PMID- 24115798
TI  - Hospital payment systems based on diagnosis-related groups: experiences in low-
      and middle-income countries.
AB  - OBJECTIVE: This paper provides a comprehensive overview of hospital payment
      systems based on diagnosis-related groups (DRGs) in low- and middle-income
      countries. It also explores design and implementation issues and the related
      challenges countries face. METHODS: A literature research for papers on DRG-based
      payment systems in low- and middle-income countries was conducted in English,
      French and Spanish through Pubmed, the Pan American Health Organization's
      Regional Library of Medicine and Google. FINDINGS: Twelve low- and middle-income
      countries have DRG-based payment systems and another 17 are in the piloting or
      exploratory stage. Countries have chosen from a wide range of imported and self
      developed DRG models and most have adapted such models to their specific
      contexts. All countries have set expenditure ceilings. In general, systems were
      piloted before being implemented. The need to meet certain requirements in terms
      of coding standardization, data availability and information technology made
      implementation difficult. Private sector providers have not been fully
      integrated, but most countries have managed to delink hospital financing from
      public finance budgeting. CONCLUSION: Although more evidence on the impact of DRG
      based payment systems is needed, our findings suggest that (i) the greater
      portion of health-care financing should be public rather than private; (ii) it is
      advisable to pilot systems first and to establish expenditure ceilings; (iii)
      countries that import an existing variant of a DRG-based system should be mindful
      of the need for adaptation; and (iv) countries should promote the cooperation of
      providers for appropriate data generation and claims management.

PMID- 24115799
TI  - Smoking-attributable mortality in Bangladesh: proportional mortality study.
AB  - OBJECTIVE: To directly estimate how much smoking contributes to cause-specific
      mortality in Bangladesh. METHODS: A case-control study was conducted with
      surveillance data from Matlab, a rural subdistrict. Cases (n = 2213) and controls
      (n = 261) were men aged 25 to 69 years who had died between 2003 and 2010 from
      smoking-related and non-smoking-related causes, respectively. Cause-specific odds
      ratios (ORs) were calculated for "ever-smokers" versus "never-smokers", with
      adjustment for education, tobacco chewing status and age. Smoking-attributable
      deaths among cases, national attributable fractions and cumulative probability of
      surviving from 25 to 69 years of age among ever-smokers and never-smokers were
      also calculated. FINDINGS: The fraction of ever-smokers was about 84% among cases
      and 73% among controls (OR: 1.7; 99% confidence interval, CI: 1.1-2.5). ORs were
      highest for cancers and lower for respiratory, vascular and other diseases. A
      dose-response relationship was noted between age at smoking initiation and daily
      number of cigarettes or bidis smoked and the risk of death. Among 25-year-old
      Bangladeshi men, 32% of ever-smokers will die before reaching 70 years of age,
      compared with 19% of never-smokers. In 2010, about 25% of all deaths observed in
      Bangladeshi men aged 25 to 69 years (i.e. 42,000 deaths) were attributable to
      smoking. CONCLUSION: Smoking causes about 25% of all deaths in Bangladeshi men
      aged 25 to 69 years and an average loss of seven years of life per smoker.
      Without a substantial increase in smoking cessation rates, which are low among
      Bangladeshi men, smoking-attributable deaths in Bangladesh are likely to
      increase.

PMID- 24115800
TI  - A cross-sectional community study of post-traumatic stress disorder and social
      support in Lao People's Democratic Republic.
AB  - OBJECTIVE: To estimate post-traumatic stress disorder (PTSD) symptoms in those
      injured and not injured by landmines or unexploded ordnance (UXO) in rural Lao
      People's Democratic Republic and to determine whether the perception of social
      support was associated with PTSD symptom severity. METHODS: A community survey
      was conducted among 190 people injured by landmines or UXO and 380 age-, sex- and
      neighbourhood-matched non-injured individuals in the Sepone district of
      Savannakhet Province, the part of the Lao People's Democratic Republic most
      heavily bombed during the Viet Nam War. Using the Harvard Trauma Questionnaire
      and the Medical Outcomes Study Social Support Survey, trained health-care workers
      conducted face-to-face interviews to assess PTSD symptoms and level of perceived
      social support. Multiple linear regression was performed to explore the
      association between social support and other factors and PTSD. FINDINGS: The
      prevalence of PTSD was higher among the injured (10%) than among the non-injured
      (4%), but the level of perceived social support was not significantly different
      between the two groups. A higher level of perceived social support was associated
      with milder symptoms of PTSD. Women, older people and those with a formal
      education were more often and more severely affected by PTSD. CONCLUSION: The
      perception of strong social support might help to alleviate the symptoms of PTSD
      among people injured by landmines or UXO in rural parts of the Lao People's
      Democratic Republic. Psychosocial interventions should be incorporated in
      assistance for the injured because they have more severe and longer-lasting
      symptoms of PTSD than the non-injured.

PMID- 24115801
TI  - Prevalences of dementia and cognitive impairment among older people in sub
      Saharan Africa: a systematic review.
AB  - OBJECTIVE: To perform a systematic review of the literature on the prevalence of
      cognitive impairment and dementia in sub-Saharan Africa. METHODS: Five electronic
      databases were searched for relevant abstracts and to identify papers eligible
      for full-text review. A study was included if two authors agreed that it had a
      cohort, case-control or cross-sectional design and reported population-level
      data; was limited to black African adults older than 50 years or described as
      "elderly" or "old"; reported data for individuals residing in sub-Saharan Africa;
      and reported at least one measure of cognitive impairment or clinical outcomes
      relevant to cognitive decline. References of papers included in our study were
      searched to identify additional candidate publications. Disagreements about
      inclusion were adjudicated during discussions involving all authors. Data were
      extracted independently by two authors, using a form developed by the authors and
      tested on a sample of papers. FINDINGS: A total of 2320 unique papers was found;
      the full text of 87 was reviewed. Nineteen papers featuring 11 cross-sectional
      studies were included; all were published during 1995-2011. Studies occurred in
      Benin, Botswana, the Central African Republic, the Congo and Nigeria and enrolled
      approximately 10,500 participants. The prevalence of dementia ranged from 0%, in
      Nigeria, to 10.1% (95% confidence interval, CI: 8.6-11.8), also in Nigeria. The
      prevalence of cognitive impairment ranged from 6.3%, in Nigeria, to 25% (95% CI:
      21.2-29.0), in the Central African Republic. CONCLUSION: Prevalences of dementia
      and cognitive impairment in sub-Saharan Africa varied widely, with few published
      studies revealed by the literature search.

PMID- 24115802
TI  - Infection surveillance after a natural disaster: lessons learnt from the Great
      East Japan Earthquake of 2011.
AB  - PROBLEM: On 11 March 2011, the Great East Japan Earthquake produced a
      catastrophic tsunami that devastated the city of Rikuzen-Takata and left it
      without an effective health infrastructure and at increased risk of outbreaks of
      disease. APPROACH: On 2 May 2011, a disease-surveillance team was formed of
      volunteers who were clinicians or members of Rikuzen-Takata's municipal
      government. The team's main goal was to detect the early signs of disease
      outbreaks. LOCAL SETTING: Seven weeks after the tsunami, 16 support teams were
      providing primary health care in Rikuzen-Takata but the chain of command between
      them was poor and 70% of the city's surviving citizens remained in evacuation
      centres. The communication tools that were available were generally inadequate.
      RELEVANT CHANGES: The surveillance team collected data from the city's clinics by
      using a simple reporting form that could be completed without adding greatly to
      the workloads of clinicians. The summary findings were reported daily to clinics.
      The team also collaborated with public health nurses in rebuilding communication
      networks. Public health nurses alerted evacuation centres to epidemics of
      communicable disease. LESSONS LEARNT: Modern health-care systems are highly
      vulnerable to the loss of advanced technological tools. The initiation--or re
      establishment--of disease surveillance following a natural disaster can therefore
      prove challenging even in a developed country. Surveillance should be promptly
      initiated after a disaster by (i) developing a surveillance system that is
      tailored to the local setting, (ii) establishing a support team network, and
      (iii) integrating the resources that remain--or soon become--locally available.

PMID- 24115803
TI  - Towards a framework convention on global health.

PMID- 24115804
TI  - Measuring maternal health: focus on maternal morbidity.

PMID- 24115805
TI  - Evidence of aqueous secondary organic aerosol formation from biogenic emissions
      in the North American Sonoran Desert.
AB  - This study examines the role of aqueous secondary organic aerosol formation in
      the North American Sonoran Desert as a result of intense solar radiation,
      enhanced moisture, and biogenic volatile organic compounds (BVOCs). The ratio of
      water-soluble organic carbon (WSOC) to organic carbon (OC) nearly doubles during
      the monsoon season relative to other seasons of the year. When normalized by
      mixing height, the WSOC enhancement during monsoon months relative to preceding
      dry months (May-June) exceeds that of sulfate by nearly a factor of 10. WSOC:OC
      and WSOC are most strongly correlated with moisture parameters, temperature, and
      concentrations of O3 and BVOCs. No positive relationship was identified between
      WSOC or WSOC:OC and anthropogenic tracers such as CO over a full year. This study
      points at the need for further work to understand the effect of BVOCs and
      moisture in altering aerosol properties in understudied desert regions.

PMID- 24115806
TI  - BRIDGING INEQUALITY FROM BOTH SIDES NOW.

PMID- 24115807
TI  - Chirp and polarization control of femtosecond molecular fragmentation.
AB  - We explore the simultaneous effect of chirp and polarization as the two control
      parameters for non-resonant photo-dissociation of n-propyl benzene. Experiments
      performed over a wide range of laser intensities show that these two control
      knobs behave mutually exclusively. Specifically, for the coherently enhanced
      fragments (C3H3+, C5H5+) with negatively chirped pulses and C6H5+ with positively
      chirped pulses, polarization effect is the same as compared to that in the case
      of transform-limited pulses. Though a change in polarization affects the overall
      fragmentation efficiency, the fragmentation pattern of n-propyl benzene molecule
      remains unaffected in contrast to the chirp case.

PMID- 24115808
TI  - Strategy for improving survival and reducing recurrence of HCV-related
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third
      leading cause of cancer-related death in the world. With advances in imaging
      diagnostics, accompanied by better understanding of high-risk patients, HCC is
      now frequently detected at an early stage; however, the prognosis remains poor.
      The recurrence rate after treatment of HCC is higher than that associated with
      cancers of other organs. This may be because of the high incidence of
      intrahepatic distant recurrence and multicentric recurrence, especially with
      hepatitis C virus (HCV)-related hepatocellular carcinoma. The Barcelona Clinic
      Liver Cancer (BCLC) classification has recently emerged as the standard
      classification system for the clinical management of patients with HCC. According
      to the BCLC staging system, curative therapies (resection, transplantation,
      transcatheter arterial chemoembolization, percutaneous ethanol injection therapy,
      percutaneous microwave coagulation therapy and percutaneous radiofrequency
      ablation) can improve survival in HCC patients diagnosed at an early stage and
      offer a potential long-term cure. However, treatment strategies for recurrent
      disease are not mentioned in the BCLC classification. The strategy for recurrence
      may differ according to the recurrence pattern, i.e., intrahepatic distant
      recurrence vs multicentric recurrence. In this article, we review recurrent HCC
      and the therapeutic strategies for reducing recurrent HCC, especially HCV-related
      HCC.

PMID- 24115809
TI  - Transjugular intrahepatic portosystemic shunt for the management of acute
      variceal hemorrhage.
AB  - Acute variceal hemorrhage, a life-threatening condition that requires a
      multidisciplinary approach for effective therapy, is defined as visible bleeding
      from an esophageal or gastric varix at the time of endoscopy, the presence of
      large esophageal varices with recent stigmata of bleeding, or fresh blood visible
      in the stomach with no other source of bleeding identified. Transfusion of blood
      products, pharmacological treatments and early endoscopic therapy are often
      effective; however, if primary hemostasis cannot be obtained or if uncontrollable
      early rebleeding occurs, transjugular intrahepatic portosystemic shunt (TIPS) is
      recommended as rescue treatment. The TIPS represents a major advance in the
      treatment of complications of portal hypertension. Acute variceal hemorrhage that
      is poorly controlled with endoscopic therapy is generally well controlled with
      TIPS, which has a 90% to 100% success rate. However, TIPS is associated with a
      mortality of 30% to 50% in such a setting. Emergency TIPS should be considered
      early in patients with refractory variceal bleeding once medical treatment and
      endoscopic sclerotherapy failure, before the clinical condition worsens.
      Furthermore, admission to specialized centers is mandatory in such a setting and
      regional protocols are essential to be organized effectively. This review article
      discusses initial management and then focuses on the specific role of TIPS as a
      primary therapy to control acute variceal hemorrhage, particularly as a rescue
      therapy following failure of endoscopic approaches. 

PMID- 24115810
TI  - Molecular targeted therapy for hepatocellular carcinoma: current and future.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide. The
      majority of HCC cases occur in patients with chronic liver disease. Despite
      regular surveillance to detect small HCC in these patients, HCC is often
      diagnosed at an advanced stage. Because HCC is highly resistant to conventional
      systemic therapies, the prognosis for advanced HCC patients remains poor. The
      introduction of sorafenib as the standard systemic therapy has unveiled a new
      direction for future research regarding HCC treatment. However, given the limited
      efficacy of the drug, a need exists to look beyond sorafenib. Many molecular
      targeted agents that inhibit different pathways involved in hepatocarcinogenesis
      are under various phases of clinical development, and novel targets are being
      assessed in HCC. This review aims to summarize the efforts to target molecular
      components of the signaling pathways that are responsible for the development and
      progression of HCC and to discuss perspectives on the future direction of
      research. 

PMID- 24115812
TI  - HER2 therapies and gastric cancer: a step forward.
AB  - Gastric cancer usually is diagnosed in advanced stages and thus current medical
      practice affords limited therapeutic options. However, recent studies established
      the role of human epidermal growth factor receptor 2 (HER2) in clinical
      management. Trastuzumab, an anti-HER2 monoclonal antibody, acquired a main role
      in advanced gastric cancer harboring HER2 overexpression and/or amplification
      improving survival to 17.1 mo according to trastuzumab for gastric cancer phase
      III trial results. Also, new promising drugs, such as c-Met inhibitors, are in
      development and assessment for this setting. Certainly, novel drugs will emerge
      in the next feel years for help oncologists improve clinical management of
      advanced gastric cancer providing higher survival and quality of life. In this
      mini-review we will discuss some issues in this regard and provide an actual
      overview of this setting.

PMID- 24115811
TI  - Endotherapy in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is a progressive disease with irreversible changes in
      the pancreas. Patients commonly present with pain and with exocrine or endocrine
      insufficiency. All therapeutic efforts in CP are directed towards relief of pain
      as well as the management of associated complications. Endoscopic therapy offers
      many advantages in patients with CP who present with ductal calculi, strictures,
      ductal leaks, pseudocyst or associated biliary strictures. Endotherapy offers a
      high rate of success with low morbidity in properly selected patients. The
      procedure can be repeated and failed endotherapy is not a hindrance to subsequent
      surgery. Endoscopic pancreatic sphincterotomy is helpful in patients with CP with
      minimal ductal changes while minor papilla sphincterotomy provides relief in
      patients with pancreas divisum and chronic pancreatitis. Extracorporeal shock
      wave lithotripsy is the standard of care in patients with large pancreatic ductal
      calculi. Long term follow up has shown pain relief in over 60% of patients. A
      transpapillary stent placed across the disruption provides relief in over 90% of
      patients with ductal leaks. Pancreatic ductal strictures are managed by single
      large bore stents. Multiple stents are placed for refractory strictures. CP
      associated benign biliary strictures (BBS) are best treated with multiple plastic
      stents, as the response to a single plastic stent is poor. Covered self expanding
      metal stents are increasingly being used in the management of BBS though further
      long term studies are needed. Pseudocysts are best drained endoscopically with a
      success rate of 80%-95% at most centers. Endosonography (EUS) has added to the
      therapeutic armamentarium in the management of patients with CP. Drainage of
      pseudcysts, cannulation of inaccessible pancreatic ducts and celiac ganglion
      block in patients with intractable pain are all performed using EUS. Endotherapy
      should be offered as the first line of therapy in properly selected patients with
      CP who have failed to respond to medical therapy and require intervention.

PMID- 24115813
TI  - Alteration in gene expression profile and oncogenicity of esophageal squamous
      cell carcinoma by RIZ1 upregulation.
AB  - AIM: To investigate the effect of retinoblastoma protein-interacting zinc finger
      gene 1 (RIZ1) upregulation in gene expression profile and oncogenicity of human
      esophageal squamous cell carcinoma (ESCC) cell line TE13. METHODS: TE13 cells
      were transfected with pcDNA3.1(+)/RIZ1 and pcDNA3.1(+). Changes in gene
      expression profile were screened and the microarray results were confirmed by
      reverse transcription-polymerase chain reaction (RT-PCR). Nude mice were
      inoculated with TE13 cells to establish ESCC xenografts. After two weeks, the
      inoculated mice were randomly divided into three groups. Tumors were injected
      with normal saline, transfection reagent pcDNA3.1(+) and transfection reagent
      pcDNA3.1(+)/RIZ1, respectively. Tumor development was quantified, and changes in
      gene expression of RIZ1 transfected tumors were detected by RT-PCR and Western
      blotting. RESULTS: DNA microarray data showed that RIZ1 transfection induced
      widespread changes in gene expression profile of cell line TE13, with 960 genes
      upregulated and 1163 downregulated. Treatment of tumor xenografts with RIZ1
      recombinant plasmid significantly inhibited tumor growth, decreased tumor size,
      and increased expression of RIZ1 mRNA compared to control groups. The changes in
      gene expression profile were also observed in vivo after RIZ1 transfection. Most
      of the differentially expressed genes were associated with cell development,
      supervision of viral replication, lymphocyte costimulatory and immune system
      development in esophageal cells. RIZ1 gene may be involved in multiple cancer
      pathways, such as cytokine receptor interaction and transforming growth factor
      beta signaling. CONCLUSION: The development and progression of esophageal cancer
      are related to the inactivation of RIZ1. Virus infection may also be an important
      factor.

PMID- 24115814
TI  - Cytokeratin 8 is increased in hepatitis C virus cells and its ectopic expression
      induces apoptosis of SMMC7721 cells.
AB  - AIM: To investigate cytokeratin 8 (CK8) overexpression during hepatitis C virus
      (HCV) infection and its pathogenesis, and the effect of ectopic CK8 expression on
      hepatoma cell lines. METHODS: We successfully established an in vitro HCV cell
      culture system (HCVcc) to investigate the different expression profiles of CK8 in
      Huh-7-HCV and Huh-7.5-HCV cells. The expression of CK8 at the mRNA level was
      determined by real-time polymerase chain reaction (RT-PCR). The expression of CK8
      at the protein level was evaluated by Western blotting. We then constructed a
      eukaryotic expression combination vector containing the coding sequence of human
      full length CK8 gene. CK8 cDNA was amplified by reverse transcription-PCR and
      inserted into pEGFP-C1 and the positive clone pEGFP-CK8 was obtained. After
      confirming the sequence, the recombinant plasmid was transfected into SMMC7721
      cells with lipofectamine2000 and CK8 expression was detected using inverted
      fluorescence microscopy, RT-PCR and Western blotting. Besides, we identified
      biological function of CK8 on SMMC7721 cells, including cell proliferation, cell
      cycle and apoptosis detection. RESULTS: RT-PCR showed that the expression level
      of CK8 in Huh-7-HCV and Huh-7.5-HCV cells was 2.88 and 2.95 times higher than in
      control cells. Western blot showed that CK8 expression in Huh-7-HCV and Huh-7.5
      HCV cells was 2.53 and 3.26 times higher than that in control cells,
      respectively. We found that CK8 at mRNA and protein levels were both
      significantly increased in HCVcc. CK8 was up-regulated in SMMC7721 cells. CK8
      expression at the mRNA level was significantly upregulated in SMMC7721/pEGFP-CK8
      cells. CK8 expression in SMMC7721/ pEGFP-CK8 cells was 2.69 times higher than in
      SMMC7721 cells, and was 2.64 times higher than in SMMC7721/pEGFP-C1 cells. CK8
      expression at the protein level in SMMC7721/pEGFP-CK8 cells was 2.46 times higher
      than in SMMC7721 cells, and was 2.29 times higher than in SMMC7721/pEGFP-C1
      cells. Further analysis demonstrated that forced expression of CK8 slowed cell
      growth and induced apoptosis of SMMC7721 cells. CONCLUSION: CK8 up-regulation
      might have a functional role in HCV infection and pathogenesis, and could be a
      promising target for the treatment of HCV infection.

PMID- 24115815
TI  - Screening pre-bariatric surgery patients for esophageal disease with esophageal
      capsule endoscopy.
AB  - AIM: To determine if esophageal capsule endoscopy (ECE) is an adequate diagnostic
      alternative to esophagogastroduodenoscopy (EGD) in pre-bariatric surgery
      patients. METHODS: We conducted a prospective pilot study to assess the
      diagnostic accuracy of ECE (PillCam ESO2, Given Imaging) vs conventional EGD in
      pre-bariatric surgery patients. Patients who were scheduled for bariatric surgery
      and referred for pre-operative EGD were prospectively enrolled. All patients
      underwent ECE followed by standard EGD. Two experienced gastroenterologists
      blinded to the patient's history and the findings of the EGD reviewed the ECE and
      documented their findings. The gold standard was the findings on EGD. RESULTS:
      Ten patients with an average body mass index of 50 kg/m(2) were enrolled and
      completed the study. ECE identified 11 of 14 (79%) positive
      esophageal/gastroesophageal junction (GEJ) findings and 14 of 17 (82%) combined
      esophageal and gastric findings identified on EGD. Fisher's exact test was used
      to compare the findings and no significant difference was found between ECE and
      EGD (P = 0.64 for esophageal/GEJ and P = 0.66 for combined esophageal and gastric
      findings respectively). Of the positive esophageal/GEJ findings, ECE failed to
      identify the following: hiatal hernia in two patients, mild esophagitis in two
      patients, and mild Schatzki ring in two patients. ECE was able to identify the
      entire esophagus in 100%, gastric cardia in 0%, gastric body in 100%, gastric
      antrum in 70%, pylorus in 60%, and duodenum in 0%. CONCLUSION: There were no
      significant differences in the likelihood of identifying a positive finding using
      ECE compared with EGD in preoperative evaluation of bariatric patients.

PMID- 24115816
TI  - Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy:
      is gastroparesis a factor?
AB  - AIM: To determine whether an increased number and duration of non-acid reflux
      events as measured using the multichannel intraluminal impedance pH (MII-pH) is
      linked to gastroparesis (GP). METHODS: A case control study was conducted in
      which 42 patients undergoing clinical evaluation for continued symptoms of
      gastroesophageal reflux disease (both typical and atypical symptoms) despite acid
      suppression therapy. MII-pH technology was used over 24 h to detect reflux
      episodes and record patients' symptoms. Parameters evaluated in patients with
      documented GP and controls without GP by scintigraphy included total, upright,
      and supine number of acid and non-acid reflux episodes (pH < 4 and pH > 4,
      respectively), the duration of acid and non-acid reflux in a 24-h period, and the
      number of reflux episodes lasting longer than 5 min. RESULTS: No statistical
      difference was seen between the patients with GP and controls with respect to the
      total number or duration of acid reflux events, total number and duration of non
      acid reflux events or the duration of longest reflux episodes. The number of non
      acid reflux episodes with a pH > 7 was higher in subjects with GP than in
      controls. In addition, acid reflux episodes were more prolonged (lasting longer
      than 5 min) in the GP patients than in controls; however, these values did not
      reach statistical significance. Thirty-five patients had recorded symptoms during
      the 24 h study and of the 35 subjects, only 9% (n = 3) had a positive symptom
      association probability (SAP) for acid/non-acid reflux and 91% had a negative
      SAP. CONCLUSION: The evaluation of patients with a documented history of GP did
      not show an association between GP and more frequent episodes of non-acid reflux
      based on MII-pH testing.

PMID- 24115817
TI  - SEMS vs cSEMS in duodenal and small bowel obstruction: high risk of migration in
      the covered stent group.
AB  - AIM: To compare clinical success and complications of uncovered self-expanding
      metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel.
      METHODS: Technical success, complications and outcome of endoscopic SEMS or cSEMS
      placement in tumor related obstruction of the duodenum or jejunum were
      retrospectively assessed. The primary end points were rates of stent migration
      and overgrowth. Secondary end points were the effect of concomitant biliary
      drainage on migration rate and overall survival. The data was analyzed according
      to the Strengthening the Reporting of Observational Studies in Epidemiology
      guidelines. RESULTS: Thirty-two SEMS were implanted in 20 patients. In all
      patients, endoscopic stent implantation was successful. Stent migration was
      observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P
      = 0.002). Stent overgrowth did not significantly differ between the two stent
      types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be
      recovered from the jejunum by way of laparotomy. Time until migration between
      SEMS and cSEMS in patients with and without concomitant biliary stents did not
      significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow
      up was 57 +/- 71 d (range: 1-275 d). CONCLUSION: SEMS and cSEMS placement is safe
      in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate
      of migration in comparison to uncovered SEMS.

PMID- 24115818
TI  - Inflammatory bowel disease serology in Asia and the West.
AB  - AIM: To study serological antibodies in Caucasians and Asians, in health and
      inflammatory bowel disease (IBD), in Australia and Hong Kong (HK). METHODS: Anti
      glycan antibodies [anti-chitobioside (ACCA), anti-laminaribioside (ALCA)], and
      anti-mannobioside (AMCA), anti-Saccharomyces cervisiae (gASCA); and atypical
      perinuclear anti-neutrophil cytoplasmic antibody (pANCA) were tested in IBD
      patients, their unaffected relatives, and healthy controls in Australia and HK
      (China). Antibody status (positive or negative) and titre was compared between
      subjects of different geography, ethnicity and disease state. RESULTS: Ninety
      subjects were evaluated: 21 Crohn's disease (CD), 32 ulcerative colitis (UC), 29
      healthy controls, and 8 IBD patient relatives. Forty eight subjects were
      Australian (29 Caucasian and 19 ethnic Han Chinese) and 42 were from HK (all Han
      Chinese). Caucasian CD patients had a significantly higher antibody prevalence of
      gASCA (67% vs 3%, P < 0.001), ALCA (44% vs 6%, P = 0.005), and AMCA (67% vs 15%,
      P = 0.002), whereas HK CD patients had a higher prevalence of only AMCA (58% vs
      25%, P = 0.035), when compared with UC and healthy subjects in both countries.
      Caucasian CD had significantly higher gASCA prevalence (67% vs 0%, P < 0.001) and
      titre (median 59 vs 9, P = 0.002) than HK CD patients. Prevalence and titres of
      ALCA, ACCA and AMCA did not differ between CD in the two countries. Presence of
      at least one antibody was higher in Caucasian than HK CD patients (100% vs 58%, P
      = 0.045). pANCA did not differ between countries or ethnicity. CONCLUSION:
      Serologic CD responses differ between HK Asian and Australian Caucasian patients.
      Different genetic, environmental or disease pathogenic factors may account for
      these differences.

PMID- 24115819
TI  - Incidence and characteristics of HBV reactivation in hematological malignant
      patients in south Egypt.
AB  - AIM: To investigate characteristics of hepatitis B virus (HBV) implicated in HBV
      reactivation in patients with hematological malignancies receiving
      immunosuppressive therapy. METHODS: Serum samples were collected from 53 patients
      with hematological malignancies negative for hepatitis B surface antigen (HBsAg)
      before the start of and throughout the chemotherapy course. HBV reactivation was
      diagnosed when the HBsAg status changed from negative to positive after the
      initiation of chemotherapy and/or when HBV DNA was detected by real-time
      detection polymerase chain reaction (RTD-PCR). For detecting the serological
      markers of HBV infection, HBsAg as well as antibodies to the core antigen (anti
      HBc) and to the surface antigen were measured in the sera by CEIA. Nucleic acids
      were extracted from sera, and HBV DNA sequences spanning the S gene were
      amplified by RTD-PCR. The extracted DNA was further subjected to PCR to amplify
      the complete genome as well as the specific genomic sequences bearing the
      enhancer II/core promoter/pre-core/core regions (nt 1628-2364). Amplicons were
      sequenced directly. RESULTS: Thirty-five (66%) of the 53 HBsAg-negative patients
      were found to be negative serologically for anti-HBc, and the remaining 18 (34%)
      patients were positive for anti-HBc. Five of the 53 (9.4%) patients with
      hematologic malignancies experienced HBV reactivation. Genotype D1 was detected
      in all five patients. Four types of mutant strains were detected in the S gene
      product of HBV strains and were isolated from 3 patients with HBV reactivation:
      T/S120, L143, and I126. HBV DNA was detected in the pretreatment HBsAg-negative
      samples in one of the five patients with HBV reactivation. In this patient,
      sequences encompassing the HBV full genome obtained from sera before the start of
      chemotherapy and at the time of de novo HBV hepatitis were detected and it showed
      100% homology. Furthermore, in the phylogenetic tree, the sequences were
      clustered together, thereby indicating that this patient developed reactivation
      from an occult HBV infection. CONCLUSION: Past infection with HBV is a risk
      factor for HBV reactivation in Egypt. Mandatory anti-HBc screening prior to
      chemotherapy in patients with hematological malignancies is recommended.

PMID- 24115820
TI  - Grasper type scissors for endoscopic submucosal dissection of gastric epithelial
      neoplasia.
AB  - AIM: To evaluate the efficacy and safety of grasper type scissors (GTS) for
      endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. METHODS:
      The study was performed by 4 endoscopists in 4 institutions affiliated to The
      Catholic University of Korea. ESD was performed in 76 consecutive patients with
      gastric epithelial neoplasia by using the GTS (37 patients) or the hook knife
      plus coagrasper (HKC) (39 patients). The complete resection rate, complication
      rate, total time elapsed and elapsed time per square centimeter of the dissected
      specimen were analyzed between the GTS and HKC group. RESULTS: The mean age of
      the GTS group was 62.3 +/- 11.4 years and mean age of the HKC group was 65.6 +/-
      10.1 years. Differentiated adenocarcinoma was found in 32.4% in the GTS group and
      33.3% in the HKC group. The procedures were performed without interruption in
      every case in both groups. The en bloc resection rates of both groups were 100%.
      The total time elapsed during the procedure was 44.54 +/- 21.72 min in the GTS
      group and 43.77 +/- 21.84 min in the HKC group (P = 0.88) and the time elapsed
      per square centimeter of the resected lesion was 7.53 +/- 6.35 min/cm(2) in the
      GTS group and 6.92 +/- 5.93 min/cm(2) in the HKC group (P = 0.66). The overall
      complication rate was not significantly different between the two groups.
      CONCLUSION: GTS is a safe and effective device for ESD compared with HKC. ESD can
      be performed with GTS alone, which can reduce the costs for ESD.

PMID- 24115821
TI  - Isolation and biochemical analysis of vesicles from taurohyodeoxycholic acid
      infused isolated perfused rat livers.
AB  - AIM: To isolate biliary lipid-carrying vesicles from isolated perfused rat livers
      after taurohyodeoxycholic acid (THDC) infusion. Biliary lipid vesicles have been
      implicated in hepatic disease and THDC was used since it increases biliary
      phospholipid secretion. METHODS: Rat livers were isolated and perfused via the
      hepatic portal vein with THDC dissolved in Krebs Ringer Bicarbonate solution, pH
      7.4, containing 1 mmol/L CaCl2, 5 mmol/L glucose, a physiological amino acid
      mixture, 1% bovine serum albumin and 20% (v/v) washed human erythrocytes at a
      rate of 2000 nmol/min for 2 h. The livers were then removed, homogenized and
      subjected to centrifugation, and the microsomal fraction was obtained and further
      centrifuged at 350000 g for 90 min to obtain subcellular fractions. These were
      analyzed for total phospholipid, cholesterol, protein and alkaline
      phosphodiesterase I (PDE). RESULTS: No significant changes were observed in the
      total phospholipid, cholesterol and protein contents of the gradient fractions
      obtained from the microsomal preparation. However, the majority of the gradient
      fractions (rho= 1.05-1.07 g/mL and rho = 1.95-1.23 g/mL) obtained from THDC
      infused livers had significantly higher PDE activity compared to the control
      livers. The low density gradient fraction (rho = 1.05-1.07 g/mL) which was
      envisaged to contain the putative vesicle population isolated from THDC-perfused
      livers had relatively small amounts of phospholipids and protein when compared to
      the relevant control fractions; however, they displayed an increase in
      cholesterol and PDE activity. The phospholipids were also isolated by thin layer
      chromatography and subjected to fractionation by high performance liquid
      chromatography; however, no differences were observed in the pattern of the fatty
      acid composition of the phospholipids isolated from THDC and control perfused
      livers. The density gradient fractions (rho = 1.10-1.23 g/mL) displayed an
      increase in all the parameters measured from both control and THDC-infused
      livers. CONCLUSION: No significant changes in biliary lipids were observed in the
      fractions from THDC-infused livers; however, PDE activity was significantly
      increased compared to the control livers.

PMID- 24115822
TI  - Nilotinib-mediated mucosal healing in a rat model of colitis.
AB  - AIM: To investigate the effects of nilotinib in a rat model of trinitrobenzene
      sulfonic acid (TNBS)-induced colitis. METHODS: Twenty-one Wistar albino female
      rats obtained from Dokuz Eylul University Department of Laboratory Animal Science
      were categorized into a control (n = 7), TNBS (n = 7) and nilotinib group (n =
      7). Saline was administered orally for 14 d to the control and the TNBS group.
      The TNBS group received rectal TNBS on the first day while saline was
      administered to the control group. The nilotinib group received 20 mg/kg
      nilotinib for 14 d in 2 divided doses, starting the same day as TNBS
      administration. For 14 d, the rats were fed a standard diet, and their weights
      were recorded daily. After sacrifice, colon tissue samples from each group were
      scored for macroscopic and microscopic pathology. Apoptotic indices were
      determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling method. Platelet-derived growth factor receptor (PDGFR) alpha and
      beta levels were assessed through immunohistochemistry staining scores and
      compared among the groups. Tissue and serum tumor necrosis factor (TNF) alpha
      levels were determined by enzyme-linked immunosorbent assay. RESULTS: Between
      days 1 and 14, the nilotinib group rats lost significantly less weight than the
      TNBS group rats (-0.7 g vs -14.0 g, P = 0.047). The difference in weight between
      the control and nilotinib groups was also statistically significant (+8.3 g vs 
      0.7 g, P = 0.031). From day 7 to day 14, the weight differences of the control
      group vs the TNBS group, the TNBS group vs the nilotinib group, and the control
      group vs the nilotinib group were all statistically significant (+8.0 g vs -11.1
      g, P = 0.007; -11.1 g vs +2.9 g, P = 0.015; +8.0 g vs +2.9 g, P = 0.042,
      respectively). Macroscopic and microscopic scores were significantly lower in the
      nilotinib group than in the TNBS group (0.00 +/- 0.00 vs 1.43 +/- 0.65, P =
      0.009; 2.86 +/- 0.55 vs 7.71 +/- 1.48, P = 0.030, respectively). However, these
      scores were similar between the nilotinib and control groups. While no
      significant difference for the nilotinib vs control groups could be determined
      for PDGFR alpha and beta scores, PDGFR alpha and beta scores were lower in the
      nilotinib group than in the TNBS group. Furthermore, the TNF alpha levels in the
      serum, tissue and apoptosis scores were similar between the nilotinib and TNBS
      groups. CONCLUSION: Nilotinib prevents weight loss, facilitates mucosal healing
      by improving the pathological scores without introducing variation into the
      apoptotic scores or TNF alpha levels.

PMID- 24115823
TI  - Lymph node metastasis in gastric cardiac adenocarcinoma in male patients.
AB  - AIM: To reveal the clinicopathological features and risk factors for lymph node
      metastases in gastric cardiac adenocarcinoma of male patients. METHODS: We
      retrospective reviewed a total of 146 male and female patients with gastric
      cardiac adenocarcinoma who had undergone curative gastrectomy with
      lymphadenectomy in the Department of Surgery, Xin Hua Hospital and Rui Jin
      Hospital of Shanghai Jiaotong University Medical School between November 2001 and
      May 2012. Both the surgical procedure and extent of lymph node dissection were
      based on the recommendations of Japanese gastric cancer treatment guidelines.
      Univariate and multivariate analyses of lymph node metastases and the
      clinicopathological features were undertaken. RESULTS: The rate of lymph node
      metastases in male patients with gastric cardiac adenocarcinoma was 72.1%.
      Univariate analysis showed an obvious correlation between lymph node metastases
      and tumor size, gross appearance, differentiation, pathological tumor depth, and
      lymphatic invasion in male patients. Multivariate logistic regression analysis
      revealed that tumor differentiation and pathological tumor depth were the
      independent risk factors for lymph node metastases in male patients. There was an
      obvious relationship between lymph node metastases and tumor size, gross
      appearance, differentiation, pathological tumor depth, lymphatic invasion at pN1
      and pN2, and nerve invasion at pN3 in male patients. There were no significant
      differences in clinicopathological features or lymph node metastases between
      female and male patients. CONCLUSION: Tumor differentiation and tumor depth were
      risk factors for lymph node metastases in male patients with gastric cardiac
      adenocarcinoma and should be considered when choosing surgery.

PMID- 24115824
TI  - Research on stress-induced apoptosis of natural killer cells and the alteration
      of their killing activity in mouse liver.
AB  - AIM: To investigate the stress-induced apoptosis of natural killer (NK) cells and
      the changes in their killing activity in mouse livers. METHODS: A restraint
      stress model was established in mice. Flow cytometry was employed to measure the
      percentage of NK cells and the changes in their absolute number in mouse liver.
      The cytotoxicity of hepatic and splenic NK cells was assessed against YAC-1
      target cells via a 4 h 51Cr-release assay. RESULTS: The restraint stress
      stimulation induced the apoptosis of NK cells in the liver and the spleen, which
      decreased the cell number. The number and percentage of NK cells in the spleen
      decreased. However, the number of NK cells in the liver decreased, whereas the
      percentage of NK cells was significantly increased. The apoptosis of NK cells
      increased gradually with prolonged stress time, and the macrophage-1 (Mac-1)(+)
      NK cells were more susceptible to apoptosis than Mac-1(-) NK cells. Large numbers
      of Mac-1(-) NK cells in the liver, which are more resistant to stress-induced
      apoptosis, were observed than the Mac-1(-) NK cells in the spleen. The stress
      stimulation diminished the killing activity of NK cells in the spleen was
      significantly decreased, but the retention of numerous Mac-1(-) NK cells in the
      liver maintained the killing ability. CONCLUSION: Significant stress-induced
      apoptosis was observed among Mac-1(+) NK cells, but not Mac-1(-) NK cells in the
      mouse liver. Stress stimulation markedly decreased the killing activity of NK
      cells in the spleen but remained unchanged in the liver.

PMID- 24115825
TI  - Interaction between cyclooxygenase-2, Snail, and E-cadherin in gastric cancer
      cells.
AB  - AIM: To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E
      cadherin in gastric cancer cells. METHODS: COX-2 expression in human gastric
      cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA
      and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent
      experiments. siRNA mediated gene knockdown was used to investigate the impact of
      COX-2 on nuclear factor-kappaB (NF-kappaB), Snail, and E-cadherin in gastric
      cancer cells. Gene expression was determined by Western blot and real-time
      polymerase chain reaction. To analyze whether NF-kappaB inhibition could
      interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E
      cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the
      presence of NF-kappaB specific siRNA. RESULTS: Highest expression level of COX-2
      was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down
      regulation of COX-2 led to a reduced expression of NF-kappaB and Snail, but an
      increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down
      regulation of NF-kappaB also led to a reduced expression of E-cadherin and Snail
      in SGC-7901 cells. However, COX-2 expression did not alter after cells were
      treated with NF-kappaB specific siRNA in SGC-7901 cells. Treatment of SGC-7901
      cells with celecoxib led to a reduced expression of Snail but an increased
      expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led
      to an increased Snail and a decreased E-cadherin. However, siRNA-mediated
      knockdown of NF-kappaB partially abolished the effect of celecoxib and PGE2 on
      the regulation of E-cadherin and Snail in SGC-7901 cells. CONCLUSION: COX-2
      likely functions upstream of NF-kappaB and regulates the expression of E-cadherin
      via NF-kappaB/Snail signaling pathway in gastric cancer cells.

PMID- 24115826
TI  - Laparoscopic vs open distal pancreatectomy for solid pseudopapillary tumor of the
      pancreas.
AB  - AIM: To compare short- and long-term outcomes of laparoscopic vs open distal
      pancreatectomy for solid pseudopapillary tumor (SPT) of the pancreas. METHODS:
      This retrospective study included 28 patients who underwent distal pancreatectomy
      for SPT of the pancreas between 1998 and 2012. The patients were divided into two
      groups based on the surgical approach: the laparoscopic surgery group and the
      open surgery group. The patients' demographic data, operative results,
      pathological reports, hospital courses, morbidity and mortality, and follow-up
      data were compared between the two groups. RESULTS: Fifteen patients with SPT of
      the pancreas underwent laparoscopic distal pancreatectomy (LDP), and 13 underwent
      open distal pancreatectomy (ODP). Baseline characteristics were similar between
      the two groups except for a female predominance in the LDP group (100.0% vs
      69.2%, P = 0.035). Mortality, morbidity (33.3% vs 38.5%, P = 1.000), pancreatic
      fistula rates (26.7% vs 30.8%, P = 0.728), and reoperation rates (0.0% vs 7.7%, P
      = 0.464) were similar in the two groups. There were no significant differences in
      the operating time (171 min vs 178 min, P = 0.755) between the two groups. The
      intraoperative blood loss (149 mL vs 580 mL, P = 0.002), transfusion requirement
      (6.7% vs 46.2%, P = 0.029), first flatus time (1.9 d vs 3.5 d, P = 0.000), diet
      start time (2.3 d vs 4.9 d, P = 0.000), and postoperative hospital stay (8.1 d vs
      12.8 d, P = 0.029) were significantly less in the LDP group than in the ODP
      group. All patients had negative surgical margins at final pathology. There were
      no significant differences in number of lymph nodes harvested (4.6 vs 6.4, P =
      0.549) between the two groups. The median follow-up was 33 (3-100) mo for the LDP
      group and 45 (17-127) mo for the ODP group. All patients were alive with one
      recurrence. CONCLUSION: LDP for SPT has short-term benefits compared with ODP.
      Long-term outcomes of LDP are similar to those of ODP.

PMID- 24115828
TI  - Endoscopic ultrasound elastography for differentiating between pancreatic
      adenocarcinoma and inflammatory masses: a meta-analysis.
AB  - AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) elastography for
      differentiating between pancreatic ductal adenocarcinoma (PDAC) and pancreatic
      inflammatory masses (PIM). METHODS: Electronic databases (updated to December
      2012) and manual bibliographical searches were carried out. A meta-analysis of
      all diagnostic clinical trials evaluating the accuracy of EUS elastography in
      differentiating PDAC from PIM was conducted. Heterogeneity was assessed among the
      studies. The meta-analysis was performed to evaluate the accuracy of EUS
      elastography in differentiating PDAC from PIM in homogeneous studies. RESULTS:
      Ten studies involving 781 patients were included in the analysis. Significant
      heterogeneity in sensitivity was observed among the studies (Cochran Q test =
      24.16, df = 9, P = 0.0041, I (2) = 62.8%), while heterogeneity in specificity was
      not observed (Cochran Q test = 5.93, df = 9, P = 0.7473, I (2) = 0.0%). The area
      under the curve under the Sports Rights Owners Coalition was 0.8227. Evaluation
      of heterogeneity suggested that the different diagnostic standards used in the
      included studies were the source of heterogeneity. In studies using the color
      pattern as the diagnostic standard, the pooled sensitivity, specificity, positive
      likelihood ratio (LR), negative LR and diagnostic OR were 0.99 (0.97-1.00), 0.76
      (0.67-0.83), 3.36 (2.39-4.72), 0.03 (0.01-0.07) and 129.96 (47.02-359.16),
      respectively. In studies using the hue histogram as the diagnostic standard, the
      pooled sensitivity, specificity, positive LR, negative LR and diagnostic OR were
      0.92 (0.89-0.95), 0.68 (0.57-0.78), 2.84 (2.05-3.93), 0.12 (0.08-0.19) and 24.69
      (12.81-47.59), respectively. CONCLUSION: EUS elastography is a valuable method
      for the differential diagnosis between PDAC and PIM. And a preferable diagnostic
      standard should be explored and improvements in specificity are required.

PMID- 24115829
TI  - Video capsule endoscopy and CT enterography in diagnosing adult hypertrophic
      pyloric stenosis.
AB  - Primary adult hypertrophic pyloric stenosis is a rare but important cause of
      gastric outlet obstruction that may be misdiagnosed as idiopathic gastroparesis.
      Clinically, patients present with early satiety, abdominal fullness, nausea,
      epigastric discomfort and eructation. Permanent gastric retention of a video
      capsule endoscope is diagnostic in differentiating between the two diseases, in
      the absence of an organic gastric outlet obstruction. This case presents the
      longest video capsule retention in the medical literature to date. It is also the
      first case report of adult hypertrophic pyloric stenosis diagnosed with video
      capsule endoscopy or a computed tomography scan. Finally, an unusual "plugging"
      of the gastric outlet with free floating capsule has an augmented effect on
      disease physiology and on patient's symptoms. 

PMID- 24115827
TI  - De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir
      monotherapy for hepatitis B virus-related decompensated cirrhosis.
AB  - AIM: To compare efficacy of combined lamivudine (LAM) and adefovir dipivoxil
      (ADV) therapy with that of entecavir (ETV) monotherapy for hepatitis B virus
      (HBV)-related decompensated liver cirrhosis. METHODS: A total of 120 naive
      patients with HBV-related decompensated cirrhosis participated in this study.
      Sixty patients were treated with combined LAM and ADV therapy (LAM + ADV group),
      while the other 60 were treated with ETV monotherapy (ETV group) for two years.
      Tests for liver and kidney function, alpha-fetoprotein, HBV serum markers, HBV
      DNA load, prothrombin time (PT), and ultrasonography or computed tomography scan
      of the liver were performed every 1 to 3 mo. Repeated measure ANOVA and the
      chi(2) test were performed to compare the efficacy, side effects, and the
      cumulative survival rates at 48 and 96 wk. RESULTS: Forty-five patients in each
      group were observed for 96 wk. No significant differences in HBV DNA negative
      rates and alanine aminotransferase (ALT) normalization rates at weeks 48 (chi(2)
      = 2.12 and 2.88) and 96 (chi(2) = 3.21 and 3.24) between the two groups were
      observed. Hepatitis B e antigen seroconversion rate in the LAM + ADV group at
      week 96 was significantly higher in the ETV group (43.5% vs 36.4%, chi(2) = 4.09,
      P < 0.05). Viral breakthrough occurred in 2 cases (4.4%) by week 48 and in 3
      cases (6.7%) by week 96 in the LAM + ADV group, and no viral mutation was
      detected. In the ETV group, viral breakthrough occurred in 1 case (2.2%) at the
      end of week 96. An increase in albumin (F = 18.9 and 17.3), decrease in total
      bilirubin and in ALT (F = 16.5, 17.1 and 23.7, 24.8), reduced PT (F = 22.7 and
      24.5), and improved Child-Turcotte-Pugh and the model for end-stage liver disease
      scores (F = 18.5, 17.8, and 24.2, 23.8) were observed in both groups. The
      cumulative rates of mortality and liver transplantation were 16.7% (10/60) and
      18.3% (11/60) in the LAM + ADV and ETV groups, respectively. CONCLUSION: Both LAM
      + ADV combination therapy and ETV monotherapy can effectively inhibit HBV
      replication, improve liver function, and decrease mortality.

PMID- 24115830
TI  - An ironic case of liver infections: Yersinia enterocolitis in the setting of
      thalassemia.
AB  - A 49 years old Vietnamese male with a history of thalassemia, presented with
      gastrointestinal symptoms and signs of hemolysis. He was diagnosed with yersinia
      enterocolitis. Yersinia is a gram-negative rod that most frequently occurs in
      children especially during the winter months. In the current case, the bone
      marrow biopsy showed hemophagocytosis along with positive cultures for Yersinia.
      The microorganism likely triggered hemophagocytosis. This syndrome, also known
      as, hemophagocytic lymphohistiocytosis, is defined by fever for more than 7 d,
      cytopenia of two or more cell lines, hemophagocytosis, hepatitis, serum ferritin
      greater than 500, jaundice, lymphadenopathy, and hepatosplenomegaly. This
      disorder can be either familial or secondary to a strong immunologic activation.
      Both have an overwhelming activation of T-cells and macrophages. 

PMID- 24115831
TI  - A case of plasmablastic lymphoma of the liver without human immunodeficiency
      virus infection.
AB  - Plasmablastic lymphoma (PBL) is a very rare B-cell lymphoproliferative disorder
      was with an aggressive clinical behavior that recently characterized by the World
      Health Organization. Although PBL is most commonly observed in the oral cavity of
      human immunodeficiency virus (HIV)-positive patients, it can also be observed at
      extra-oral sites in HIV-negative patients. Epstein-Barr virus (EBV) may be
      closely related the pathogenesis of PBL. PBL shows different clinicopathological
      characteristics between HIV-positive and -negative patients. Here, we report a
      case of PBL of the liver in a 79-year-old HIV-negative male. The patient died
      approximately 1.5 mo after examination and autopsy showed that the main lesion
      was a very large liver mass. Histopathological examination of the excised lesion
      showed large-cell lymphoma with plasmacytic differentiation diffusely
      infiltrating the liver and involving the surrounding organs. The neoplastic cells
      were diffusely positive for CD30, EBV, Bob-1, and CD38. The autopsy findings
      suggested a diagnosis of PBL. To our knowledge, the present case appears to be
      the first report of PBL with initial presentation of the liver in a patient
      without HIV infection.

PMID- 24115832
TI  - Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the
      stomach: case report and literature review.
AB  - The combination of classical Hodgkin's lymphoma (cHL) and non-Hodgkin lymphoma
      coexisting in the same patient is not common, especially in one extranodal
      location. Here we present a rare case of composite diffuse large B-cell lymphoma
      (DLBCL) and cHL occurring simultaneously in the stomach of a 53-year-old female
      who presented with upper abdominal discomfort and gas pain. Surgery was performed
      and the disease was diagnosed pathologically as composite lymphoma of DLBCL and
      cHL using hematoxylin-eosin and immunohistochemical staining. Epstein-Barr virus
      (EBV) infection was not detected by in situ hybridization for EBV-encoded RNA or
      immunohistochemistry for EBV latent membrane protein-1. Polymerase chain reaction
      analysis from the two distinct components of the tumor demonstrated clonal
      immunoglobulin kappa light chain gene rearrangements. The patient died
      approximately 11 mo after diagnosis in spite of receiving eight courses of the
      CHOP and two courses of the rituximab-CHOP (RCHOP) chemotherapy regimen. This
      case report showed that the two distinct components, DLBCL and cHL, appeared to
      originate from the same clonal progenitor cell, and that EBV infection was not
      essential for transformation during the course of tumorigenesis.

PMID- 24115833
TI  - Giant biliary cystadenoma complicated with polycystic liver: a case report.
AB  - Biliary cystadenoma (BCA) is a rare hepatic neoplasm. Although considered a
      benign cystic tumor of the liver, BCA has a high risk of recurrence with
      incomplete excision and a potential risk for malignant degeneration. Correct
      diagnosis and complete tumor excision with negative margins are the mainstay of
      treatment. Unfortunately, due to the lack of presenting symptoms, and normal
      laboratory results in most patients, BCA is hard to distinguish from other cystic
      lesions of the liver such as biliary cystadenocarcinoma, hepatic cyst, hydatid
      cyst, Caroli disease, undifferentiated sarcoma, intraductal papillary mucinous
      tumor, and hepatocellular carcinoma. Ultrasound (US), computed tomography (CT)
      and magnetic resonance imaging (MRI) may be necessary. They demonstrate
      intrahepatic cystic lesions with features such as mural nodules, varying wall
      thickness, papillary projections, and internal septations. Nevertheless, surgery
      is still the only means of accurate diagnosis. Definitive diagnosis requires
      histological examination following formal resection. We describe a 57-year-old
      woman initially diagnosed with polycystic liver who was subsequently diagnosed
      with giant intrahepatic BCA in the left hepatic lobe. This indicates that both US
      physicians and hepatobiliary specialists should attach importance to hepatic
      cysts, and CT or MRI should be performed for further examination when a diagnosis
      of BCA is suspected. 

PMID- 24115834
TI  - The evaluation of two commercially available, portable Raman systems.
AB  - Raman spectroscopy and surface enhanced Raman spectroscopy (SERS) have many
      attributes that make them attractive for field detection of environmental
      contaminants, industrial process control, as well as materials
      detection/identification in agriculture, pharmaceuticals, law enforcement/first
      responders, geology, and archeology. However, portable, robust, inexpensive Raman
      systems are required for these applications. In this communication, the
      performances of two commercially available, portable Raman systems are evaluated.

PMID- 24115835
TI  - Anti-insulin-like growth factor-IIP3 DNAzymes inhibit cell proliferation and
      induce caspase-dependent apoptosis in human hepatocarcinoma cell lines.
AB  - BACKGROUND: Insulin-like growth factor II (IGF-II) is a fetal growth protein and
      an important proangiogenic factor controlled by four promoters (P), of which P2
      P4 are inactive in the adult liver. Reactivation and dysregulation of IGF-IIP3 in
      particular is associated with the attenuation of apoptosis and increased
      proliferation in a number of liver cancer cell types. Its involvement in
      experimental liver carcinogenesis makes it a potential target for cancer gene
      therapy. We designed two IGF-IIP3 specific DNAzymes (DRz1 and DRz2) that target
      IGF-IIP3 messenger RNA (mRNA) with the aim of reducing IGF-II expression through
      promoter 3. METHODS: IGF-IIP3 mRNA and protein expression levels were assessed
      using real-time polymerase chain reaction and gel electrophoresis/western
      blotting after transfection with Lipofectamine(r) in SMMC-7721, Huh7, and HepG2
      cell lines. Cell proliferation was determined via MTT assay; apoptosis was
      evaluated by fluorescence microscopy and with flow cytometry; procaspase-3 and -9
      expression were detected via western blotting; and caspase activity was assayed
      colorimetrically. Standard procedures were used to calculate means and standard
      deviations, and P-values below 0.05 were considered to indicate significant
      differences. RESULTS: DRzs were transfected into hepatocellular carcinoma cells
      and the results showed that DRz1, in particular, could decrease the expression of
      IGF-IIP3 by nearly 50%. Furthermore, DRz1 significantly inhibited cell
      proliferation and induced apoptosis. In addition, the down-regulation of IGF-IIP3
      expression was associated with increased caspase-3 and -9 activity in SMMC-7721
      cells after 24 hours of transfection. In all experiments, the efficacy of DRz2 to
      influence IGF-IIP3 levels and associated effects remained second to DRz1.
      CONCLUSION: Overall, these results suggest that DRz1-based targeting of IGF-IIP3
      mRNA might have antitumorigenic activity and may potentially provide the basis
      for a novel therapeutic intervention in liver cancer treatment, although further
      development is required.

PMID- 24115836
TI  - Clinical experimentation with aerosol antibiotics: current and future methods of
      administration.
AB  - Currently almost all antibiotics are administered by the intravenous route. Since
      several systems and situations require more efficient methods of administration,
      investigation and experimentation in drug design has produced local treatment
      modalities. Administration of antibiotics in aerosol form is one of the treatment
      methods of increasing interest. As the field of drug nanotechnology grows, new
      molecules have been produced and combined with aerosol production systems. In the
      current review, we discuss the efficiency of aerosol antibiotic studies along
      with aerosol production systems. The different parts of the aerosol antibiotic
      methodology are presented. Additionally, information regarding the drug molecules
      used is presented and future applications of this method are discussed. 

PMID- 24115838
TI  - The effect of prostaglandin analogs on the biomechanical properties and central
      thickness of the cornea of patients with open-angle glaucoma: a 3-year study on
      108 eyes.
AB  - PURPOSE: To evaluate the effect of prostaglandin analogs (PGAs) on the
      biomechanical properties (corneal hysteresis [CH], corneal resistance factor
      [CRF]) and central corneal thickness (CCT) of patients with open-angle glaucoma.
      METHODS: A total of 108 eyes were prospectively included for repeated
      measurements of intraocular pressure (IOP) with Goldmann applanation tonometry
      (GAT) and ocular response analyzer (ORA), CCT, followed by CH and CRF
      measurements by the ORA, during the same visit. Of these, 66 were treated with
      latanoprost, and 42 were treated with latanoprost and timolol. IOP, CH, CRF, and
      CCT were measured before treatment and at 6-month intervals. RESULTS: It appears
      that under local PGA treatment, IOP values decreased and CH and CCT significantly
      increased, whereas CRF did not. CCT slightly but significantly increased at all
      time points of the study (0.50-3.00 MUm and 1.50-5.50 MUm), and we observed a
      constant significant increase in CH (0.4-0.7 mmHg and 0.65-0.95 mmHg). Concerning
      the correlation of GAT IOP with CCT and CH, it was found that at the time points
      0, 1, and 2 there were statistically significant correlations. CONCLUSION: The
      changes of CCT and CH under PGA treatment in clinical practice may influence IOP
      measurements and patient follow-up significantly. This should be investigated
      further to confirm the relationship between corneal properties and treatment of
      open-angle glaucoma.

PMID- 24115837
TI  - The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and
      emerging therapeutics to control low-density lipoprotein cholesterol.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) directly binds to the
      epidermal growth factor-like repeat A domain of low-density lipoprotein receptor
      and induces its degradation, thereby controlling circulating low-density
      lipoprotein cholesterol (LDL-C) concentration. Heterozygous loss-of-function
      mutations in PCSK9 can decrease the incidence of coronary heart disease by up to
      88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss
      of-function mutations on both alleles, resulting in a total absence of functional
      PCSK9, were found to have extremely low circulating LDL-C levels without other
      apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective
      pharmacological target to increase clearance of LDL-C and to reduce the risk of
      coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal
      antibodies that block the PCSK9:low-density lipoprotein receptor interaction were
      shown to considerably reduce LDL-C levels by up to 65% when given alone and by up
      to 72% in patients already receiving statin therapy. In this review, we will
      discuss how major scientific breakthroughs in PCSK9 cell biology have led to the
      development of new and forthcoming LDL-C-lowering pharmacological agents. 

PMID- 24115842
TI  - Investing for the financially challenged: A punter asks the right question.

PMID- 24115840
TI  - Estimating the modulatory effects of nanoparticles on neuronal circuits using
      computational upscaling.
AB  - BACKGROUND: Beside the promising application potential of nanotechnologies in
      engineering, the use of nanomaterials in medicine is growing. New therapies
      employing innovative nanocarrier systems to increase specificity and efficacy of
      drug delivery schemes are already in clinical trials. However the influence of
      the nanoparticles themselves is still unknown in medical applications, especially
      for complex interactions in neural systems. The aim of this study was to
      investigate in vitro effects of coated silver nanoparticles (cAgNP) on the
      excitability of single neuronal cells and to integrate those findings into an in
      silico model to predict possible effects on neuronal circuits. METHODS: We first
      performed patch clamp measurements to investigate the effects of nanosized silver
      particles, surrounded by an organic coating, on excitability of single cells. We
      then determined which parameters were altered by exposure to those nanoparticles
      using the Hodgkin-Huxley model of the sodium current. As a third step, we
      integrated those findings into a well-defined neuronal circuit of thalamocortical
      interactions to predict possible changes in network signaling due to the applied
      cAgNP, in silico. RESULTS: We observed rapid suppression of sodium currents after
      exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium
      currents we identified the parameters likely affected by cAgNP. We then examined
      the effects of such changes on the activity of networks. In silico network
      modeling indicated effects of local cAgNP application on firing patterns in all
      neurons in the circuit. CONCLUSION: Our sodium current simulation shows that
      suppression of sodium currents by cAgNP results primarily by a reduction in the
      amplitude of the current. The network simulation shows that locally cAgNP-induced
      changes result in changes in network activity in the entire network, indicating
      that local application of cAgNP may influence the activity throughout the
      network.

PMID- 24115839
TI  - 8-Hydroxyquinolines: a review of their metal chelating properties and medicinal
      applications.
AB  - Metal ions play an important role in biological processes and in metal
      homeostasis. Metal imbalance is the leading cause for many neurodegenerative
      diseases such as Alzheimer's disease, Parkinson's disease, and multiple
      sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic
      effect and a metal chelating ability. As a result, 8HQ and its derivatives hold
      medicinal properties such as antineurodegenerative, anticancer, antioxidant,
      antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse
      bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed
      together with their mechanisms of actions and structure-activity relationships. 

PMID- 24115843
TI  - A comparison of pulse oximetry and laser Doppler flowmetry in monitoring
      sequential vascular occlusion in a rabbit ear model.
AB  - The ultimate success of any free flap transfer depends not only on the experience
      of the given surgical team, but also requires constant vigilance in the
      perioperative period to assure continued anastomotic patency. Clinical acumen
      remains the 'industry' standard, but adjunctive monitoring devices are important
      to reinforce these subjective evaluations. We routinely use laser Doppler
      flowmetry in spite of known drawbacks, including expense. On the other hand, we
      know that pulse oximetry is a possible and readily available alternative. The
      efficacy of these two monitoring systems was directly compared in a New Zealand
      white rabbit central artery and vein ear model. Arterial occlusion was
      immediately recognized by a precipitous drop in flow and oxygen saturation
      (SaO2). A rapid drop in flow after venous occlusion with a trend to zero was also
      noted with laser Doppler flowmetry. The SaO2 had a very slow but steady gradual
      decline, but values remained in the range of normoxemia for a prolonged time.
      Because a minimum threshold of SaO2 for predicting venous occlusion was elusive,
      the usefulness of pulse oximetry for monitoring microsurgical composite tissue
      transfers is limited. 

PMID- 24115841
TI  - Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a member of the TNF superfamily, was the
      first cytokine to be evaluated for cancer biotherapy. However, the clinical use
      of TNF-alpha is severely limited by its toxicity. Currently, TNF-alpha is
      administered only through locoregional drug delivery systems such as isolated
      limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of
      TNF-alpha, various strategies have been explored over the last several decades.
      This review summarizes current state-of-the-art targeted cancer therapy using TNF
      alpha. Passive targeting, cell-based therapy, gene therapy with inducible or
      tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting,
      antibody-TNF-alpha conjugate, scFv/TNF-alpha fusion proteins, and peptide/TNF
      alpha fusion proteins have all been investigated to combat cancer. Many of these
      agents are already in advanced clinical trials. Molecular imaging, which can
      significantly speed up the drug development process, and nanomedicine, which can
      integrate both imaging and therapeutic components, has the potential to
      revolutionize future cancer patient management. Cooperative efforts from
      scientists within multiple disciplines, as well as close partnerships among many
      organizations/entities, are needed to quickly translate novel TNF-alpha-based
      therapeutics into clinical investigation.

PMID- 24115845
TI  - An assessment of the anatomical basis of the thoracoacromial artery perforator
      flap.
AB  - BACKGROUND: Musculocutaneous perforator flaps offer advantages over
      musculocutaneous flaps, including reduced donor site morbidity, more predictable
      reconstruction of soft tissue deformities, and a wider variety of flap options.
      Perforator flaps are becoming increasingly popular for many applications. In the
      present study, we set out to examine the various perforators of the
      thoracoacromial axis through the pectoralis major (PM) muscle with respect to
      their suitability for transfer to the head and neck region as a pedicled flap.
      METHODS: A series of 10 fresh cadavers were injected with lead oxide, gelatin and
      water (250 mL/kg) through the femoral vessels. The cadavers were cooled and the
      integument was removed. Perforating vessels from the underlying muscles were
      marked and the resulting angiograms of the integument and deep tissues were
      compared with the dissection notes describing the course, size and distribution
      of the perforating vessels. RESULTS: THE PERFORATORS THROUGH THE PM MUSCLE TO THE
      OVERLYING SKIN INCLUDED THREE REGIONAL GROUPS: perforators of the thoracoacromial
      axis; perforators of the medial intercostal vessels; and perforators of the
      lateral thoracic artery. The major group of perforators supplying the overlying
      skin was from the intercostal vessels. However, the thoracoacromial axis did
      consistently give rise to perforators in the upper portion of the PM muscle. In
      particular, there were reliable perforators from the clavicular and deltoid
      branches of the thoracoacromial artery. DISCUSSION: The present study illustrates
      the potential clinical applications of a series of perforator flaps based on the
      thoracoacromial axis, which may be useful in head and neck reconstructive
      surgery.

PMID- 24115844
TI  - The effects of cold preservation and subimmunosuppressive doses of FK506 on
      axonal regeneration in murine peripheral nerve isografts.
AB  - BACKGROUND: FK506 is a frequently used immunosuppressant with neuroregenerative
      effects. The neuroregenerative and immunosuppressive mechanisms of FK506,
      however, are distinct, suggesting that FK506 may stimulate nerve regeneration at
      lower doses than are needed to induce immunosuppression. The effects of cold
      preservation, a technique known to improve axonal regeneration through nerve
      allografts, are not well studied in nerve isografts and are also reported here.
      OBJECTIVES: To determine the effects of subimmunosuppressive doses of FK506 and
      cold preservation on nerve regeneration in isografts. METHODS: The
      neuroregenerative properties of immunosuppressive and subimmunosuppressive doses
      of FK506 were compared in a murine model receiving either fresh or cold preserved
      nerve isografts. Sixty female BALB/cJ mice were randomized into six groups.
      Animals in groups I, III and V received fresh nerve isografts. Animals in groups
      II, IV and VI received cold-preserved nerve isografts. Mice in groups I and II
      received no medical therapy, while those in groups III and IV received
      subimmunosuppressive doses of FK506, and those in groups V and VI received
      immunosuppressive doses as confirmed by mixed lymphocyte reactivity assays. Nerve
      regeneration was evaluated with histomorphometry and functional recovery was
      evaluated with walking track analysis. RESULTS: Pretreatment with cold
      preservation did not significantly affect neural regeneration. The potent
      neuroregenerative effect of immunosuppressive doses of FK506 was confirmed, and
      the ability of subimmunosuppressive doses of FK506 to stimulate axonal
      regeneration in murine nerve isografts is reported. CONCLUSIONS: Less toxic
      subimmunosuppressive doses of FK506 retaining some neuroregenerative properties
      may have a clinical role in treating extensive nerve injuries.

PMID- 24115846
TI  - Applied anatomy of the fasciocutaneous branch of the third perforator artery of
      the deep femoral artery.
AB  - A study of the anatomy of the fasciocutaneous branch of the third perforator
      artery of the deep femoral artery was performed to help the elaboration of a
      fasciocutaneous flap for the reconstruction of skin and subcutaneous and deep
      fascia of the knee and popliteal region. Forty thighs in 27 fresh cadavers were
      dissected. In all of the thighs, the third perforator artery was found to arise
      from the deep femoral artery and reach the posterior aspect of the thigh after
      perforating the adductor magnus muscle. At that point it was also found that the
      third perforator artery gives off a branch that emerges through the intermuscular
      septum between the vast lateral muscle and the long head of the biceps femoral
      muscle, then crosses the posterior cutaneous nerve and moves directly on to
      perforate the deep fascia and then to bifurcate into two other branches: one
      ascending and one descending. The cutaneous area of the flap of the thigh's
      posterior region, nourished by the fasciocutaneous branch, was evaluated through
      the injection of dye. Dying of the upper medial, middle medial, lower medial and
      lower lateral areas of the flap was not successful in all of the dissected
      thighs. Nevertheless, the upper lateral and the middle lateral areas were dyed
      successfully in all 40 dissected thighs of the 27 cadavers. 

PMID- 24115847
TI  - Reducing patient discomfort during digital blockade: The subcutaneous single
      injection digital block - A simple, safe and fast procedure.
AB  - BACKGROUND: Regional anesthesia of a single finger is commonly achieved by the
      traditional ring block, which requires at least two painful injections in the
      digit. Single injection digital block techniques have been described to avoid
      this problem. Among these, the subcutaneous technique described by Harbison
      appears to be safe and to allow most procedures to be carried out with good
      tolerance. OBJECTIVES: A prospective study was designed to evaluate the results
      of the subcutaneous technique in terms of patient tolerance, distribution of
      anesthesia and efficiency. METHODS: All blocks were performed by a single
      investigator. A visual analog scale was used to evaluate pain associated with the
      injection. Prick testing was used to evaluate the quality of anesthesia at the
      volar and dorsal aspects of the phalanxes. Tolerance to the surgical procedure
      and the need for additional injections were also recorded. RESULTS: This
      technique allowed surgery to be performed without complementary injection most of
      the time and was very well tolerated. The dorsum of the proximal phalanx,
      however, was unpredictably included in the anesthetized territory. CONCLUSION:
      The subcutaneous single injection digital block is safe, efficient and easy to
      perform. It allows the treatment of all conditions on the volar aspect of the
      finger and on the dorsal aspect of the distal and middle phalanxes. For surgery
      on the dorsal aspect of the proximal phalanx, a combined single injection
      technique or a supplementary dorsal block should be used.

PMID- 24115848
TI  - Recurrent venous thrombosis following free flap surgery: The role of heparin
      induced thrombocytopenia.
AB  - Complications following free tissue transfer have been well established in the
      literature. Common and rare causes of free flap failure must be addressed by the
      treating surgeon when microvascular patency is threatened. With the evolution and
      prevalence of microsurgery, 'rare' causes of free flap failure will become
      increasingly frequent. A high index of suspicion must be established in patients
      with multiple failed operative interventions. A case of recurrent free flap
      failure secondary to heparin-induced thrombocytopenia is presented in a patient
      with a history of squamous cell carcinoma of the floor of the mouth, and a long
      standing history of alcohol and tobacco consumption. 

PMID- 24115849
TI  - Cutaneous myiasis due to Dermatobium hominis in Winnipeg.
AB  - Cutaneous myiasis is an uncommon infestation in North America, with most cases
      arising in travelers who have recently returned from Central and South America.
      The majority of cases are due to Dermatobium hominis and present with a
      furunculoid nodule with local inflammation. The case reported is of a 57-year-old
      woman with cutaneous myiasis contracted in Winnipeg, Manitoba. 

PMID- 24115850
TI  - Giant eccrine acrospiroma: A case report and review of the literature.
AB  - BACKGROUND: Acrospiromas are histologically distinct cutaneous tumours of sweat
      duct origin and usually measure 1 to 2 cm in size. OBJECTIVE: We describe a
      patient with a large benign eccrine acrospiroma. METHODS: Case report and
      literature review. RESULTS: A 50-year-old woman underwent excision of a 5.5*5.0
      cm cystic mass located on the left gluteal region, and the resulting defect was
      closed by a local flap. A diagnosis of benign eccrine acrospiroma was made after
      histopathological examination. On histological examination, the lesion was
      characterized by multilobular dermal masses composed of a biphasic cell
      population. There was no recurrence five months after the operation. CONCLUSION:
      Although eccrine acrospiromas are usually benign, they can, on rare occasions,
      undergo malignant transformation. In addition, the clinical appearance of this
      lesion is not specific and differential diagnosis from other lesions, both benign
      and malignant, can only be done after the complete removal of the lesion.

PMID- 24115853
TI  - Money and quality in health care: Muttered medical musings from the back of the
      class.

PMID- 24115851
TI  - Synovial chondromatosis of the hand: Three case reports and literature review.
AB  - Synovial chondromatosis is a rare condition that is probably caused by synovial
      connective tissue metaplasia. It is very rare in the hand and wrist and because
      of its low prevalence and nonspecific symptoms, synovial chondromatosis can
      present diagnostic difficulties for the hand surgeon and may lead to a delay in
      treatment. We review the literature and report three additional cases of synovial
      chondromatosis in the hand. 

PMID- 24115854
TI  - Early major complications of endoscopic carpal tunnel release: A review of 1200
      cases.
AB  - Although the early benefits of endoscopic carpal tunnel release have been
      demonstrated, there is great controversy regarding the risks and safety of the
      technique. The present study reports early major complications in a series of
      1278 consecutive cases performed by a single surgeon over a seven-year period.
      All procedures were performed under local anaesthesia on an outpatient basis
      using the Agee single portal technique. Mean follow-up was three months. No
      vascular, tendon or permanent nerve injuries were documented. Recurrent or
      persistent symptoms occurred in 7% of patients for which 20 of 89 underwent
      subsequent open carpal tunnel release. No nerve injuries were found on re
      exploration. Other complications were consistent with previously reported
      incidences. This is the largest reported case series by a single surgeon and
      represents an accumulation of surgical experience at the upper end of the
      learning curve. Endoscopic carpal tunnel release is a safe procedure in this
      experienced single surgeon series. 

PMID- 24115855
TI  - Breast reconstruction in Nova Scotia: Rate, trends and influencing factors.
AB  - BACKGROUND: During their lifetime, approximately 10% of Canadian women will
      develop breast cancer. An increased awareness of breast reconstruction in
      patients undergoing mastectomy appears to have increased the demand for breast
      reconstructive surgery. OBJECTIVES: To study the rate of breast reconstructive
      surgeries performed in the province of Nova Scotia to determine whether the
      breast reconstructive services now offered are adequate to meet the needs of the
      population of this area. METHODS: The number of breast reconstruction procedures
      and mastectomies completed in the province of Nova Scotia during the time period
      of 1992 to 2001 was reviewed. The data were obtained from Maritime Medical Care
      Incorporated, the provincial medical plan. Information available on patients
      coded as undergoing breast surgeries was reviewed (n=10,056). The data on the
      trends and demographics of the Nova Scotia population were obtained from
      Statistics Canada. The data on incidence, prevalence and trends of breast cancer
      were obtained from the Canadian Cancer Society and the National Cancer Institute
      of Canada. RESULTS AND CONCLUSIONS: There is strong evidence of an increasing
      trend in the number of reconstructive surgeries among the women who underwent
      mastectomy. The number of breast reconstruction procedures increased 15 fold
      during the study period. This is mainly attributed to the increased awareness of
      women undergoing mastectomy and improved education by surgeons, family physicians
      and breast cancer support groups. Health sector employees must evaluate these
      trends to determine if the breast reconstructive services currently offered in
      this region are adequate. Reconstructive surgery was negatively associated with
      increasing age. Place of residency (urban versus rural) seems to play a role in
      women's decisions to proceed with breast reconstruction.

PMID- 24115856
TI  - Free flaps for head and neck cancer reconstruction: Does the use of both large
      cervical vessels as recipient vessels and the employment of end-to-side technique
      enhance flap survival?
AB  - This study specifically investigates whether the use of both large cervical
      vessels (the external carotid artery and the internal jugular vein) as recipient
      vessels with end-to-side anastomosis enhance free flap survival in head and neck
      cancer reconstruction, when compared with the use of other standard smaller neck
      recipient vessels and end-to-end anastomosis. A total of 84 consecutive patients
      were included and were divided into two groups (42 in each group) according to
      the recipient vessels. The overall vessel thrombosis rate was 6% (five of 84
      cases) and the overall flap loss rate was 2.4% (two of 84 cases) yielding a flap
      salvage rate of 60%. Vessel thrombosis occurred in three cases of the smaller
      vessels group and in two cases of the large cervical vessels group. This was not
      statistically significant. 

PMID- 24115857
TI  - Post-traumatic stenosing flexor tenosynovitis.
AB  - Two cases of post-traumatic stenosing flexor tenosynovitis (flexor tendon
      entrapment or trigger digit) are presented. The medical literature contains few
      reports of this uncommon etiology for a problem that afflicts at least 2% of the
      adult population. 

PMID- 24115858
TI  - Ischemia of the hand secondary to radial artery thrombosis: A report of three
      cases.
AB  - Upper extremity arterial thrombosis, though rare, is more prevalent on the ulnar
      side of the circulation, with the most common etiology being repetitive blunt
      trauma to the hypothenar eminence. Radial artery thrombosis is even more rare and
      when it does occur, is associated most often with iatrogenic cannulation,
      producing subsequent thrombi and emboli. Three cases of spontaneous thrombosis of
      the radial artery extending to the superficial palmar arch and the princeps
      pollicis artery are presented here. Two patients underwent thrombectomies and one
      underwent excision of the thrombosed segment and reconstruction with a reversed
      saphenous vein graft. The etiology of the thrombus was consistent with cancer in
      two cases and trauma in one. 

PMID- 24115859
TI  - Extensor digitorum brevis manus: A case of fourth-compartment syndrome.
AB  - The presence of an extensor digitorum brevis manus represents a variation of the
      normal anatomy of the fourth extensor compartment of the wrist. It usually
      presents as a swelling on the dorsum of the wrist and is often inaccurately
      diagnosed. An awareness of its existence and of its characteristic appearance on
      diagnostic imaging studies is the basis for diagnosis. Symptomatic cases require
      division of the extensor retinaculum or excision of the muscle, depending on
      subtype, while asymptomatic cases require no intervention. 

PMID- 24115860
TI  - Eccrine porocarcinoma: A case report and review of the literature.
AB  - Eccrine porocarcinoma is a rare form of skin cancer that is often confused with
      other types of skin malignancy. The present paper highlights a typical case to
      remind plastic surgeons of the natural history, pathological findings and current
      literature on the management of this cancer. 

PMID- 24115861
TI  - A giant lymphangioma circumscriptum on the anterior axilla: A case report.
AB  - Lymphangioma is a rare benign proliferative lymphatic lesion that appears in
      chronic lymphedematous states in a variety of settings. Lymphangioma
      circumscriptum consists of clinically thin-walled, translucent vesicles appearing
      in groups most commonly located on the axilla, chest, mouth, and tongue. A 12
      year-old male patient had been suffering from itching, pink-red colored,
      translucent vesicular lesions overlying the anterior axilla since birth. The
      lesions had slowly grown in size and number over the years. The patient had no
      history of trauma, or cellulites. The physical examination revealed clusters of
      pink-red colored vesicles, which released a clear exudate when punctured. The
      lesion was 50*120 mm in size. The lesion was totally excised and repaired with Z
      plasty. Histopathological examination revealed slight epidermal acanthosis and
      enlarged lymph in the upper dermis, impinging directly onto the epidermis. These
      lymphatics were lined only by endothelium. The lower dermis and sub-cutis
      contained abnormally large muscle-coated vessels containing a proteinaceous
      fluid. Six months later, there was no recurrence and a cosmetically and
      functionally acceptable postoperative result was obtained. 

PMID- 24115862
TI  - Estimating implant size in chin augmentation: A simplified approach.
AB  - A receding chin, colloquially known as a weak chin, is a significant aesthetic
      impediment to a pleasing face. Multiple techniques exist to evaluate the poorly
      projecting chin, but most are imprecise when it comes to choosing the proper
      implant size. This choice is further complicated by the impracticality of
      commercially available chin implants. Most implant manufacturers offer only three
      to four categories of implants (small, medium, large, etc) that differ in size
      from one company to another, making the choice of the proper implant size a real
      challenge. The present paper discusses a new approach to precise sizing of the
      chin implant, based primarily on the degree of chin convexity (curvature of the
      chin pad) in the profile view. Examples of mentoplasties performed using the chin
      convexity principle are presented. 

PMID- 24115864
TI  - The luckiest generation.

PMID- 24115863
TI  - Transconjunctival approach in lower eyelid blepharoplasty.
AB  - AIM: To specify interest and indications of the transconjunctival approach in
      lower-eyelid plastic surgery. MATERIALS AND METHODS: Twenty-three cases of
      inferior blepharoplasty performed through a transconjunctival approach are
      reported. The authors describe the surgical technique, its indications and
      results. RESULTS: The transconjunctival approach provides excellent access to the
      inferior fatty chambers and is cutaneous scar free. It has a lower complication
      rate than the classic transcutaneous approach, and no case of cyclid retraction
      has been reported. CONCLUSION: In our 'cosmetic society', the inferior
      blepharoplasty through a transconjunctival approach has taken a significant place
      in the armamentarium of the esthetic surgeon. Juvenile palpebral lipoptosis
      without skin excess constitutes the best indication for this technique. It is
      also indicated in secondary blepharoplasty and in patients presenting with a
      cicatricial risk or with orbital septum distention.

PMID- 24115865
TI  - Dimethyl sulfoxide and oxidative stress on cultures of human keratinocytes.
AB  - OBJECTIVES: The aim of the present study was to examine the protective action of
      the antioxidant dimethyl sulfoxide (DMSO) against the oxidative stress on
      keratinocyte cultures caused by glucose deprivation and hypoxia, using the
      concentration of malonyl dialdehyde existing in the cell culture as an indicator
      of the oxidative stress level. METHODS: EIGHTY FLASKS WITH CULTURED HUMAN
      KERATINOCYTES IN A CONFLUENT LAYER WERE DIVIDED INTO EIGHT GROUPS, INCLUDING THE
      FOLLOWING: culture medium with and without glucose, culture medium with and
      without the addition of DMSO, culture medium subjected and not subjected to
      hypoxia, and culture medium with a combination of these factors. RESULTS AND
      CONCLUSIONS: The statistical analysis of the results showed that DMSO proved to
      be an effective agent against the oxidative stress on cultures of keratinocytes
      under the experimental conditions studied.

PMID- 24115866
TI  - Vitamin C and oxidative stress on cultured human keratinocytes.
AB  - The aim of this research was to study the hypoxia-induced oxidative stress on
      cultured human keratinocytes. Control and cultured human keratinocytes were
      treated with vitamin C, and were then assessed by determining the concentration
      of malonyl dialdehyde (a final product of lipid peroxidation) existing in the
      cultured environment. Forty-eight flasks with culture of keratinocytes in
      confluent layer were divided into four groups: one control and one experimental
      group treated with vitamin C, and one control and one experimental group without
      vitamin C. All the cultures were sampled for malonyl dialdehyde assessment
      immediately after the end of a 30 min period of hypoxia. The statistical analysis
      of the results showed that vitamin C was not an effective protective agent
      against oxidative stress caused by hypoxia. 

PMID- 24115867
TI  - Custom prefabrication of silicone tubes from urinary catheters for experimental
      peripheral nerve surgery.
AB  - The entubulation principle represents a neurobiological approach to nerve surgery
      in which the role of the surgeon is limited and intrinsic healing capabilities of
      the nerve play the primary role. Herein, a technique for fabricating custom-made
      silicone tubes from a silicone urinary catheter is described. Silicone tubes with
      varying size and dimensions can be tailored depending on the diameter of the
      silicone urinary catheter (14 F to 18 F). Tubes crafted from silicone urinary
      catheters were used either as a nerve conduit to facilitate regeneration or as
      compressive nerve banding to simulate compressive neuropathy in the rat sciatic
      nerve. Custom-made silicone tubes have similar pros and cons to the commercially
      available silicone tubes regarding the capsule and foreign body reaction. It can
      be concluded that these cost effective tubes can be easily cut and used in
      experimental peripheral nerve surgery in developing countries where the cost of
      such materials becomes an important issue for the researchers. 

PMID- 24115868
TI  - Why do free flap vessels thrombose? Lessons learned from implantable Doppler
      monitoring.
AB  - BACKGROUND: Before implantable venous Doppler monitoring, by the time the failing
      flap was explored, thrombosis had often occurred and therefore the cause of flap
      flow cessation was often difficult to determine. The Doppler allowed the
      detection of flow cessation in failing flaps before thrombosis occurred in every
      case since the authors started using it in 1999. OBJECTIVES: To review the
      authors' experiences with the implantable venous Doppler. METHODS: The authors
      reviewed 43 free flaps in 40 consecutive patients (1999 to 2002) in which the
      implantable venous Doppler was used. All cases were performed at the Saint John
      Regional Hospital, Saint John, New Brunswick, by the senior author. Data were
      collected from the hospital and office charts. RESULTS: The Doppler detected
      inadequate blood flow in nine free flaps. In five of the cases, the cause was a
      kink in the vein. Repositioning the vein to get rid of the kink salvaged all five
      flaps. In the sixth case, compression of the vein after insetting was detected
      and successfully corrected. Flow cessation in the seventh case was attributable
      to arterial vasospasm, which was also salvaged. In the last two cases, the cause
      was low flow in the flap from the time the vessel clamps were let go. In spite of
      patent anastomoses, these two flaps were lost because there was not enough flow
      to sustain them. CONCLUSION: The implantable venous Doppler has allowed
      intraoperative detection of free flap vessel flow cessation, identification of
      the reasons for, and the correction of these prethrombotic states.

PMID- 24115869
TI  - The indications and reliability of vein graft use in free flap transfer.
AB  - BACKGROUND: Adequate recipient vessels are critical for free flap success. There
      are, however, situations in which the local recipient vessels are inadequate. In
      these situations, vein grafts are required to allow pedicle extension to
      recipient vessels. OBJECTIVES: To determine the indications, technique,
      reliability and outcome of vein graft use in free flap transfer. METHODS: A
      retrospective review of 198 consecutive free flaps by a single surgeon. RESULTS:
      Vein grafts were required in 9.6% of free flaps. The most common indication was
      vein graft use in a planned preoperative fashion. The vein graft was most commony
      placed as an arteriovenous fistula loop. There was no statistically significant
      difference in survival between flaps with or without vein grafts. CONCLUSION:
      Vein graft use in free flap transfer is reliable, effective and often necessary
      for free flap survival.

PMID- 24115870
TI  - Transfer of either index finger extensor tendon to the extensor pollicis longus
      tendon.
AB  - BACKGROUND: Extensor pollicis longus (EPL) tendon ruptures have been treated
      succesfully with the transfer of the extensor indicis proprius (EIP) tendon.
      Situations exist in which, due to intraoperative observations, another tendon
      transfer may be considered preferable to the standard EIP transfer method.
      OBJECTIVES: To determine whether transfer of the extensor digitorum communis II
      (EDC II) tendon from the index finger to the EPL tendon, leaving the EIP tendon
      to the index finger intact, would serve as an equally efficient transfer and not
      adversely affect the function of the hand. METHODS: Two patients who had the EDC
      II tendon transferred to the ruptured EPL tendon, and two patients who had the
      EIP tendon transferred, were retrospectively reviewed. In each transfer type, one
      patient had suffered an EPL tendon rupture after a Colles' fracture, and the
      other had rheumatoid arthritis. The rupture occurred on the non-dominant side in
      one patient in each transfer type. Each patient was examined and subjected to
      range of motion and power testing at least one year following surgery. RESULTS:
      All four patients showed a minimal extension lag with the lift off test, but
      there was no noticeable difference in range of motion, pinch grip and hand grip
      strength between the transfer types. Both EDC II transfer patients demonstrated
      an 8 degrees  to 15 degrees  loss of thumb interphalangeal joint flexion compared
      with the unoperated side; EIP transfer patients demonstrated less than a 5
      degrees  loss. Three patients demonstrated a minor extension lag in the index
      finger and middle finger. Extension power of the thumb and index finger in all
      patients varied with wrist flexion and extension and ranged from 50% to 150% of
      the unoperated side. CONCLUSIONS: These case reports suggest that either index
      finger tendon may be successfully transferred in EPL tendon ruptures.

PMID- 24115871
TI  - Treatment of electrical burns by single debridement followed by free-flap
      coverage: How important is timing?
AB  - BACKGROUND: High-voltage electrical burns involving the extremities may cause
      marked loss of skin and subcutaneous tissue exposing underlying bone and tendon.
      Treatment of electrical burns has historically involved serial debridement with
      late wound closure. Success has been reported with the use of microvascular free
      flap transfer within three days of injury. OBJECTIVE: Seven patients with severe
      high-voltage electrical burns are presented. The application and timing of
      microvascular free-flap coverage is discussed. RESULTS: Six of the seven patients
      achieved successful healing with the free flaps. CONCLUSION: Delay of
      microvascular free-flap coverage beyond the previously published three-day
      protocol may not dramatically affect treatment success.

PMID- 24115872
TI  - Reflex sympathetic dystrophy syndrome associated with burns of the upper
      extremity.
AB  - Reflex sympathetic dystrophy syndrome is an ill-defined symptom complex with
      clinical manifestations of excessive pain, joint stiffness and soft tissue
      changes. It rarely manifests following burns. Diagnosis is usually made from
      clinical symptoms and ganglion block. Early diagnosis and institution of
      conservative management is required to control symptoms and disability. 

PMID- 24115873
TI  - The use of polymethyl-methacrylate (Artecoll) as an adjunct to facial
      reconstruction.
AB  - BACKGROUND: Injectable polymethyl-methacrylate (PMMA) microspheres, or Artecoll,
      has been used for the last few years in aesthetic surgery as long-term tissue
      filler for the correction of wrinkles and for lip augmentation. This paper
      presents three cases of the use of PMMA microsphere injection for reconstructive
      patients with defects of varying etiologies. These cases provide examples of a
      novel adjunct to the repertoire of the reconstructive surgeon. OBJECTIVES: To
      evaluate the effectiveness (short- and long-term) of PMMA injection for the
      correction of small soft tissue defects of the face. METHODS: Three case
      histories are presented. They include the origin of the defect; previous
      reconstructions of the defect; and area, volume, timing and technical
      particularities of PMMA administration. RESULTS: All three cases showed
      improvement of the defect with the PMMA injection with respect to both objective
      evidence and patient satisfaction. The improvements can still be seen after
      several years. CONCLUSIONS: PMMA microsphere injection can be effectively used to
      correct selected small facial defects in reconstructive cases and the results are
      long lasting.

PMID- 24115874
TI  - Necrotizing fasciitis following a motor vehicle accident with Candida species as
      the sole organisms.
AB  - Necrotizing soft-tissue infections exclusively due to Candida species are rare
      and not usually considered in the differential diagnosis of this devastating
      condition. When documented previously, Candida species are generally proposed to
      be a saprophytic component of multibacterial synergistic infection often
      associated with streptococcal species. We report a case of a 51-year-old man who
      developed necrotizing fasciitis secondary to Candida infection following a motor
      vehicle accident. His clinical presentation was very similar to that of
      clostridial gas gangrene. The only organisms isolated from tissue culture were
      Candida albicans and Candida tropicalis. Histopathology confirmed yeast forms and
      pseudohyphae within the debrided tissue specimens. No bacteria were identified on
      any of the wound swabs or tissue specimens. Our report is the first that reveals
      Candida as the sole identifiable cause for necrotizing fasciitis following
      trauma. Candida should be considered in the differential diagnosis of causative
      organisms for necrotizing fasciitis and infective myonecrosis. 

PMID- 24115876
TI  - Working for free.

PMID- 24115875
TI  - Use of groin flap in the closure of through and through defect of a forearm: A
      case report.
AB  - The groin flap is a vascularized axial flap based on the superficial circumflex
      iliac artery arising from the femoral artery just below the inguinal ligament. It
      is used regularly by many reconstructive surgeons for covering soft tissue
      defects of the hand. Although the development of various fasciocutaneous free
      flaps during the 1980s decreased the attractiveness of the groin flap, these
      flaps can be used in reconstructing significant defects of the forearm and hand
      where free tissue transfer is not feasible. 

PMID- 24115877
TI  - Avulsion of the flexor digitorum tendon secondary to enchondroma of the distal
      phalanx.
AB  - Flexor digitorum profundus (FDP) tendon avulsion is a common injury in sports.
      This is secondary to forced extension against flexor digitorum profundus
      contraction. However, avulsion injury of the FDP tendon secondary to an
      enchondroma of the distal phalanx is extremely rare. There have only been three
      previous reports of such an occurrence. This report describes a fourth case of an
      avulsion injury of the FDP tendon secondary to enchondroma of the distal phalanx
      of the fourth digit. 

PMID- 24115878
TI  - Posterior interosseous nerve compression secondary to a parosteal lipoma: Case
      report and literature review.
AB  - An unusual case of limited radial nerve palsy secondary to a parosteal lipoma is
      presented, along with a thorough review of the literature. Palsy of the posterior
      interosseous nerve secondary to compression by a lipoma is a rare occurrence.
      Most cases tend to occur in the fifth to eighth decades of life. The pattern of
      physical symptoms may be quite variable. A high degree of suspicion must be
      maintained in the setting of unexplained symptoms. The literature review revealed
      the presence of a diagnostic proximal forearm radiolucent mass in 13 of 15
      patients. Although they are used as diagnostic aids, computed tomography and
      magnetic resonance imaging have not been shown to alter management. Though benign
      tumours constitute a minority of such cases, a plain radiograph is recommended in
      addition to electromyographic and nerve conduction studies. 

PMID- 24115879
TI  - Endometriosis in the canal of Nuck: Atypical manifestations in an unusual
      location.
AB  - The canal of Nuck is an embryological remnant of the processus vaginalis and has
      been described as a site for endometriosis seeding. Endometriosis localized to
      the canal of Nuck is exceedingly rare with three cases reported. The case of a 31
      year-old woman with an endometrioma in the canal of Nuck, made diagnostically
      challenging by atypical imaging and clinical findings, is described. 

PMID- 24115880
TI  - Gorlin's syndrome: An interesting case study and literature review.
AB  - Gorlin's syndrome, or basal cell nevus syndrome, is a relatively rare disease. It
      consists of a classic pentad of features comprised of multiple basal cell
      carcinomas, jaw cysts, calcification of the falx cerebri, pitting of the palmar
      and plantar surfaces and rib anomalies. A review of the clinical features,
      differential diagnosis, clinical work-up and current treatment is presented. 

PMID- 24115881
TI  - Lymphedema of the upper extremity following circumferential burns.
AB  - Lymphedema is characterized by edema of the extremity due to the inability of the
      lymphatic system to remove lymph into the circulation. This condition can result
      from destruction of the superficial lymphatics from burn injury and recurrent
      infection of the extremity. Due to its rare occurrence, two cases of upper
      extremity lymphedema following burns are reported. 

PMID- 24115883
TI  - Patient safety in plastic surgery.

PMID- 24115882
TI  - Johanson-Blizzard syndrome: A challenge in nasal reconstruction.
AB  - Johanson-Blizzard syndrome is rare and involves multiple congenital anomalies,
      including bilateral absence or deficiency of the nasal alae, giving the affected
      infant a characteristic appearance. Two cases are described that illustrate the
      difficulties of nasal reconstruction in young children. Surgical options and the
      timing of intervention are discussed. 

PMID- 24115884
TI  - Skin wound healing, ischemia-reperfusion injury and nerve regeneration:
      Similarities in the sequential events and molecular basis.
AB  - Skin wound healing, ischemia-reperfusion injury and nerve regeneration are three
      important topics for the hand surgeon. The events and molecular basis for each of
      these three topics are very complex, and previous review articles have discussed
      each topic separately. The present review demonstrates and comments on the
      similarities in the sequential events and molecular basis among skin wound
      healing, ischemia-reperfusion injury and nerve regeneration. 

PMID- 24115886
TI  - Ketamine-diazepam protocol for intravenous sedation: The cosmetic surgery
      hospital experience.
AB  - Rising hospital costs and operating room scheduling difficulties have influenced
      plastic surgeons to rely more often on intravenous sedation in office surgical
      settings. The use of ketamine as an intravenous sedation agent has enjoyed some
      popularity, but this has been far from universal. Its reputation for producing
      psychological sequelae such as nightmares, flashbacks and schizophrenic-like
      reactions have made many anesthesiologists and plastic surgeons reluctant to use
      this drug. The authors' experience using a ketamine/diazepam protocol with
      approximately 11,400 patients since 1971 at the Cosmetic Surgery Hospital in
      Woodbridge, Ontario is presented. The methodology consists of intravenous
      diazepam followed with low-dose ketamine (0.5 mg/kg to a maximum of 40 mg) 2 min
      later. This provides the surgeon with a period of profound amnesia to allow for
      infiltration of the local anesthetic. It is this local anesthetic delivered
      during the dissociative state that provides prolonged analgesia throughout the
      surgery. The patient is maintained throughout the procedure with increments of
      diazepam and midazolam. This protocol is found to be effective, reliable and
      reproducible, and the experience of the patient and plastic surgeon has been
      overwhelmingly favourable. 

PMID- 24115885
TI  - A review of materials currently used in orbital floor reconstruction.
AB  - Orbital fractures are common fractures of the midface. As such, numerous
      techniques and materials exist for the repair of this region, each with inherent
      advantages and disadvantages. But does the ideal implant material exist? Should
      we stop and simply use readily available materials, or should the cycle of need
      and discovery continue? A comprehensive review of materials used in orbital
      reconstruction and possible new directions in orbital floor reconstruction are
      presented. 

PMID- 24115887
TI  - Minimal invasive surgery for gynecomastia - A novel approach.
AB  - During the past three decades, there has been a gradual evolution toward less
      invasive surgery. In breast surgery, the introduction of vacuum-assisted biopsy
      devices with larger bore cannulae has extended their role to include a
      therapeutic as well as a diagnostic function. The present article focuses on the
      innovative use of vacuum-assisted biopsy devices in the treatment of male mammary
      hypertrophy. 

PMID- 24115888
TI  - Acute median nerve compression neuropathy from a foreign body in the forearm.
AB  - Acute compression of the median nerve in the forearm usually occurs from
      compartment syndrome. A case of acute compression neuropathy of the median nerve
      from a foreign body, where there was no evidence of compartment syndrome, is
      reported. The diagnosis was made from the patient's symptoms and radiographs.
      Early recognition and decompression of the forearm with removal of the foreign
      body led to full recovery. 

PMID- 24115889
TI  - Necrotizing fasciitis: Diagnosis and management of an occult infective focus.
AB  - Necrotizing fasciitis is a life-threatening, fulminant disease that is a
      diagnostic and therapeutic challenge. Presenting with a triad of findings
      including progressive erythema, severe dermatological edema and severe pain
      disproportionate to the physical findings, this disease is a surgical emergency.
      Delayed diagnosis and surgical debridement lead to higher mortality. Early
      extensive surgical debridement, aggressive antibiotic therapy, invasive
      monitoring and intensive care management determine the outcome in most cases. In
      patients who fail to demonstrate clinical improvement, profound sepsis and its
      sequela -systemic inflammatory response - have frequently been implicated. It is
      these patients that need to be carefully re-evaluated for 'hidden' foci of
      infection that may be the real cause of the patient's decline. Once detected,
      these occult foci can be surgically debrided, resulting in dramatic improvement.
      Two illustrative cases, one with occult endo- and panophthalmitis and the other
      with an unusual involvement of deeper muscle planes and the nodal basin,
      demonstrate this point. This consumptive process gathers momentum at an alarming
      speed, hence, the treatment must be aggressive and prompt. 

PMID- 24115890
TI  - Strengthening the bond with our American colleagues.

PMID- 24115891
TI  - Live surgery.

PMID- 24115892
TI  - Extensor quadriga: Pathomechanics and treatment.
AB  - The extensor tendons to the index, long, ring and small fingers are motored by
      the common extensor digitorum communis muscle body. Effective function of this
      muscle can only occur if the gliding amplitude of each of its four extensor
      tendons is normal. As a corollary, limitation of the excursion of any of the
      individual tendons by adhesions at a fracture or tendon repair site, a fixed
      flexion contracture at the metacarpophalangeal joint, or by rupture, attenuation
      or laceration of a saggital band or juncturae tendinum, will result in reduction
      of the excursion of the adjacent extensor tendons. This pathological state has
      been termed the extensor quadriga because of its similarities to the analogous
      pathology affecting the flexor digitorum profundus system. Improper management of
      this clinical entity may lead to an abnormal pathomechanical kinematic chain
      imbalance. Early identification and treatment is critical to address this entity
      appropriately. 

PMID- 24115893
TI  - A methodological guide to performing a cost-utility study comparing surgical
      techniques.
AB  - BACKGROUND: When recommending the adoption of a new surgical intervention as
      opposed to maintaining an old one, surgeons need to consider the opportunity
      cost, which is the value of the forgone benefits. To inform these decisions,
      surgeons can use economic analyses of surgical practices. Unfortunately, economic
      analyses conducted alongside randomized controlled trials in surgery are rare.
      OBJECTIVES: The objective of the present study was to use data from a small
      randomized controlled trial to illustrate the methodology for a cost-utility
      analysis comparing two techniques of carpal tunnel release: open release without
      ('usual' technique) and with ('novel' technique) ligament reconstruction.
      METHODS: Eighteen eligible patients were entered into this prospective study.
      Fifteen were followed to six weeks postoperatively. One day preoperatively, and
      five days, three weeks and six weeks postoperatively, patients completed a self
      administered Health Utilities Index Mark 2-3 questionnaire (utilities) and a case
      report form from which resource utilization (cost) was collected. Utilities were
      expressed as quality-adjusted life weeks, a fraction of quality-adjusted life
      years. RESULTS: The mean total cost of the usual technique was lower than the
      novel technique, and the mean quality-adjusted life week was higher, favouring
      the usual technique. Indirect costs were four to nine times higher than direct
      costs in both techniques. CONCLUSION: The novel technique was more costly and
      less effective, and fell in the 'lose-lose' quadrant of the cost-effectiveness
      plane; it was rejected in favour of the usual technique. This methodology should
      be applied when deciding whether to adopt novel surgical techniques in plastic
      surgery to optimize scarce health care resources.

PMID- 24115894
TI  - A mature and fast-forming fibrous capsule using tetracycline: A preliminary
      report.
AB  - The most frequently used method in two-stage reconstruction of a tendon is the
      placement of a silicone rod, forming a canal where the tendon can glide easily,
      that is subsequently replaced with a tendon graft. However, there is a
      disadvantage in that the formation of a qualified gliding canal requires at least
      three months after the placement of the silicone rod. In the present report, the
      authors evaluated the effects of tetracycline on the time period required for the
      formation of a qualified gliding canal in rats after the placement of a silicone
      rod. Tetracycline was administered through an 18 gauge needle inserted into the
      silicone rod in the test side (right) and saline solution was administered in the
      same fashion to the control side (left) in each rat. Histopathological and
      macroscopic examinations at weeks 1, 2, 3, 4 and 8 after the operation showed
      that a significantly thicker and more mature sheath was formed after two weeks in
      the sides that had been treated with tetracycline. 

PMID- 24115895
TI  - Absence of capsular contracture in 319 consecutive augmentation mammaplasties:
      Dependent drains as a possible factor.
AB  - Capsular contracture is one of the major complications of augmentation
      mammaplasty. A review of 638 augmented breasts in 319 consecutive patients who
      underwent primary augmentation, with an average follow-up of 17.2 months and
      without a single case of capsular contracture of any degree to date, is
      presented, along with a discussion of the surgical technique and complications,
      and an analysis of measures used to prevent capsular contraction. Each patient
      received a pair of smooth saline-filled implants (Mentor, USA) placed in the
      submuscular space through an inframammary incision. In all operated breasts, many
      of the known measures commonly used for capsular contracture prevention were
      implemented. As well, a dependent drain was used as the final hemostatic step to
      prevent blood accumulation in the pocket. Leaving a dependent drain in the
      dissected pocket overnight, as one of the sequence of measures aimed at
      eliminating blood accumulation, is believed to be a contributing factor in
      capsular contracture prevention. 

PMID- 24115896
TI  - Juvenile xanthogranuloma of the nose.
AB  - Juvenile xanthogranuloma is a type of non-Langerhans cell histiocytosis that
      occurs most frequently in infants and children. It is usually asymptomatic and
      can present as either a cutaneous or extracutaneous lesion. The present case is
      believed to be the first reported in the English literature of juvenile
      xanthogranuloma presenting as an ulcerated bleeding lesion on the dorsum of the
      nose. 

PMID- 24115897
TI  - A case of epiphora and recurrent basal cell carcinoma of the nasal tip and review
      of acquired nasolacrimal system obstruction.
AB  - A case of a 67-year-old man with recurrent basal cell carcinoma of the nasal tip
      and an incidental symptom of epiphora (volunteered by the patient) is presented.
      Epiphora is an abnormal overflow of tears that fail to drain into the inferior
      nasal meatus via the nasolacrimal system. Within the differential diagnosis of
      epiphora and nasolacrimal obstruction is neoplasm - primary, secondary or
      metastatic. On further investigation, including computed tomography imaging, he
      was subsequently found to have invasive disease extending along the left
      embryological cleavage plane superiorly to the medial canthal tendon. An excision
      attempt using Mohs technique by the dermatological surgeon was unsuccessful in
      adequately clearing the margins, and revealed a diagnosis of morphea-like basal
      cell cancer. This failure, taken together with the extent of disease identified
      by computed tomography scan, resulted in significant alteration of the operative
      approach. The patient underwent extensive tumour extirpation and nasal
      reconstruction using a forehead flap. The present case alerts surgeons involved
      in the management of skin cancers to the importance of the anatomical
      relationship of the nasolacrimal apparatus to embryological soft tissue cleavage
      planes when dealing with recurrent and aggressive lesions. In addition, it serves
      as a reminder to inquire about the signs and symptoms associated with
      nasolacrimal obstruction. Moreover, when preparing for surgical excision of
      recurrent aggressive basal cell carcinoma, high-quality imaging is essential to
      tailor the operative plan. 

PMID- 24115898
TI  - Severe myositis ossificans in a paraplegic trauma patient: Influence in pressure
      sore management.
AB  - Myositis ossificans (MO) is a benign, progressive, ossifying lesion that displays
      a characteristic zonal histological appearance. MO traumatica is a localized form
      of heterotopic bone formation, associated with repetitive micro- and/or
      macrotrauma in the majority of cases. The importance of imaging to differentiate
      MO from sarcomatous change and to determine maturity of the lesion is identified
      because suboptimal operative intervention on immature MO inevitably results in
      recurrence. A severe case of MO in a 24-year-old paraplegic man with chronic
      bilateral greater trochanteric pressure sores is presented, and the importance of
      the MO in the etiology and treatment of this case is discussed. An extensive
      review of the literature is included and integrated. 

PMID- 24115899
TI  - Scalp ulceration from a circumferential head dressing after craniotomy: Case
      report of an uncommon complication due to human error.
AB  - The present paper describes a previously unpublished complication of the
      application of a circumferential head dressing after cranial neuro-surgery. A 34
      year-old woman developed a large area of skin necrosis on her forehead from a
      circumferential head dressing applied after the surgical removal of a colloid
      cyst. Neurological recovery was excellent but plastic surgical repair of her
      iatrogenic cosmetic injury was required. 

PMID- 24115900
TI  - Capillary electrophoresis as a screening tool for alpha amylase inhibitors in
      plant extracts.
AB  - Capillary electrophoresis (CE) method was developed for screening plant extract
      for potential alpha amylase (AA) inhibitory activity. The method was validated
      against a well established UV method. Overall, the proposed method was shown able
      to detect plants with significant alpha amylase inhibitory activity but not those
      with rather clinically insignificant activities. Fifty plant species were
      screened using both the proposed CE method and the UV method and seven plant
      species were found to possess significant AA inhibitory activities. Two plant
      species were proved to have alpha amylase inhibitory activity for the first time.

PMID- 24115901
TI  - Effect of Kollidon(r) SR on the release of Albuterol Sulphate from matrix
      tablets.
AB  - The objective of this study was to evaluate Kollidon SR for the development of
      extended release Albuterol Sulphate matrix tablets in comparison with other
      polymers as Hydroxypropylmethylcellulose K15M, Carbopol 71G NF, and Eudragit L100
      55. The mechanical properties of the tablets were improved as concentration of
      Kollidon SR or other polymers increased. It was found that Kollidon SR 30% (w/w)
      and HPMC 30% (w/w) tablets have f 2 similarity factor of 83.5 in their Albuterol
      Sulphate dissolution profile. The marketed product was found to release 99.7% of
      drug content within 8 h, while Kollidon SR and HPMC tablets with 30% (w/w)
      polymer concentration level released 92.7% and 92.9% respectively of drug content
      within 8 h. Kollidon SR has a unique character of maintaining tablets geometric
      shape until the end of dissolution test, this is mainly due to the water
      insoluble content, polyvinyl acetate, forming 80% (w/w) of Kollidon SR, while the
      remaining content 20% (w/w) is the water soluble, polyvinylpyrrolidone,
      responsible for pore formation causing a diffusion controlled release. Drug
      release from all previous formulations is best described to be controlled by more
      than one kinetic mechanism of release. In conclusion, Kollidon SR and HPMC and
      Carbopol were found to be potential candidates for the development of extended
      release of Albuterol Sulphate tablets. 

PMID- 24115902
TI  - Formulation and in vitro evaluation of theophylline matrix tablets prepared by
      direct compression: Effect of polymer blends.
AB  - The deformation mechanism of pharmaceutical powders, used in formulating directly
      compressed matrix tablets, affects the characteristics of the formed tablets.
      Three polymers of different deformation mechanisms were tested for their impact
      on theophylline directly compressed tablets namely Kollidon SR (KL SR, plastic
      deformation), Ethylcellulose (EC, elastic deformation) and Carnauba wax (CW,
      brittle deformation) at different compression forces. However, tablets based
      mainly on KL SR, the plastically deformed polymer (TN1) exhibited the highest
      hardness values compared to the other formulae which are based on either blends
      of KL SR with CW, the very brittle deformed polymer. The upper detected force for
      TN formulae and the lower punch force were found to dependent mainly on the
      powder deformation. This difference is attributed to the work done during the
      compression phase as well as the work lost during the decompression phase.
      Furthermore, the release profiles of TN from formulae TN2 and TN4 that are based
      on the composition (2KL SR:1EC) and (1KL SR:2EC), respectively, were consistent
      with different deformation mechanisms of KL SR and EC and on the physicochemical
      properties like the water absorptive capacity of EC. Upon increasing the weight
      ratio of KL SR (TN2), the release rate was greatly retarded (39.4%, 37.1%, 35.0%
      and 33.6% released after 8 h at 5, 10, 15 and 20 kN. 

PMID- 24115903
TI  - Development of sustained release antipsychotic tablets using novel polysaccharide
      isolated from Delonix regia seeds and its pharmacokinetic studies.
AB  - A natural polysaccharide was isolated from the seeds of Delonix regia. The
      isolated polysaccharide could maintain aqueous equilibrium between the dosage
      form and the surrounding medium due to its massive competence of water absorption
      (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a
      polysaccharide exhibits rough surface with pores and crevices, hence, the drug
      release will be retarded because of the drug particles entrapment in the pores
      and crevices. Further, the surface tension of polysaccharide is higher than that
      of water, which may facilitate sustained release of drugs from dosage forms. An
      antipsychotic drug, quetiapine fumarate has a short half-life of 6 h and
      administered multiple times per day. Hence the quetiapine fumarate oral sustained
      release tablets were formulated using this polysaccharide in the concentration of
      5-30% to avoid the side effects and increase patient compliance. Dissolution of
      the developed tablets with 25% polysaccharide content showed a better release
      profile than the other batches (5-20%) at the end of 12 h. The strong matrix
      complex has low solubility in water, it does not dissolve rapidly and the drug
      continues to diffuse through the gel layer at a consistent rate. Drug release
      from the matrix tablets follows matrix type except F-4 and F-5 which follow first
      order and Hix.crow type. The bioavailability study was carried out using healthy
      male New Zealand white rabbits that show the AUC(0-inf) value for developed SR
      tablets is 1.44 times higher than the reference thus, indicating more efficient
      and sustained drug delivery capable of maintaining plasma drug levels better. 

PMID- 24115904
TI  - Extractive spectrophotometric assay of cyclizine in a pharmaceutical formulation
      and biological fluids.
AB  - Two highly sensitive and simple spectrophotometric methods were developed to
      quantitate the drug cyclizine (CYC) in its pure form and in a pharmaceutical
      formulation. The two methods involved ion-associate formation reactions (method
      A) with mono-acid azo dyes, i.e., sudan (I) and sudan (II), as well as ion-pair
      reactions (method B) with bi-azo dyes, i.e., sudan (III), sudan (IV) and sudan
      red 7B (V). The reactions were extracted with chloroform, and the extraction
      products were quantitatively measured at 480, 550, 500, 530 and 570 nm using
      reagents I-V, respectively. The reaction conditions were monitored and optimised.
      The Beer plots for reagents I-V showed linear relationships for the
      concentrations of 4.2-52.0, 5.4-96.0, 3.5-43.0, 4.4-80.0 and 0.6-18.0 MUg mL(-1),
      respectively, with molar absorptivities of 2.2 * 10(4), 4.1 * 10(4), 3.6 * 10(4),
      2.5 * 10(4) and 1.3 * 10(4) L mol(-1) cm(-1), respectively. Sandell sensitivities
      and detection limits were calculated and analysed. The implementation of the two
      methods to the analysis of a commercial tablet (Valoid) succeeded, and the
      recovery study suggested that there was no interference from common excipients in
      the tablet. Regarding the accuracy and precision of the methods, a statistical
      comparison of the results was performed using Student's t-test and the F-test at
      the 95% confidence level. The accuracy and precision of the proposed methods were
      not significantly different. 

PMID- 24115905
TI  - Biosorption of heavy metals by Bacillus thuringiensis strain OSM29 originating
      from industrial effluent contaminated north Indian soil.
AB  - The study was navigated to examine the metal biosorbing ability of bacterial
      strain OSM29 recovered from rhizosphere of cauliflower grown in soil irrigated
      consistently with industrial effluents. The metal tolerant bacterial strain OSM29
      was identified as Bacillus thuringiensis following 16S rRNA gene sequence
      analysis. In the presence of the varying concentrations (25-150 mgl(-1)) of heavy
      metals, such as cadmium, chromium, copper, lead and nickel, the B. thuringiensis
      strain OSM29 showed an obvious metal removing potential. The effect of certain
      physico-chemical factors such as pH, initial metal concentration, and contact
      time on biosorption was also assessed. The optimum pH for nickel and chromium
      removal was 7, while for cadmium, copper and lead, it was 6. The optimal contact
      time was 30 min. for each metal at 32 +/- 2  degrees C by strain OSM29. The
      biosorption capacity of the strain OSM29 for the metallic ions was highest for Ni
      (94%) which was followed by Cu (91.8%), while the lowest sorption by bacterial
      biomass was recorded for Cd (87%) at 25 mgl(-1) initial metal ion concentration.
      The regression coefficients obtained for heavy metals from the Freundlich and
      Langmuir models were significant. The surface chemical functional groups of B.
      thuringiensis biomass identified by Fourier transform infrared (FTIR) were amino,
      carboxyl, hydroxyl, and carbonyl groups, which may be involved in the biosorption
      of heavy metals. The biosorption ability of B. thuringiensis OSM29 varied with
      metals and was pH and metal concentration dependent. The biosorption of each
      metal was fairly rapid which could be an advantage for large scale treatment of
      contaminated sites. 

PMID- 24115906
TI  - On the Configurational Stability of Chiral Heteroatom-Substituted
      [D1]Methylpalladium Complexes as Intermediates of Stille and Suzuki-Miyaura Cross
      Coupling Reactions.
AB  - Enantiomerically pure (S)-tributylstannyl[D1]methanol and (R)- and (S)
      tributylstannyl[D1]methyl benzoates were Stille-coupled with bromobenzene and
      benzoyl chloride in 1,4-dioxane and toluene using [(Ph3P)4Pd] or [(Ph3P)2PdCl2]
      either alone or in combination with CuCN as cocatalyst at temperatures up to 80 
      degrees C. The products were found to be enantiomerically pure. (R)- and (S)-N
      (tributylstannyl[D1]methyl)phthalimides gave enantiomerically pure products with
      benzoyl chloride, but with bromobenzene protected phenyl[D1]methylamines gave
      products of only 52-69 % ee depending on the solvent used.
      Tributyl(thio[D1]methyl)stannanes could not be Stille-coupled with benzoyl
      chloride or with bromobenzene. Similarly, dimethyl phenyl[D1]methylboronate
      underwent a Suzuki-Miyaura coupling with bromobenzene to give
      phenyl[D1]methylsilane with 99 % ee. All couplings followed a retentive course
      and, except in one case, the intermediate [XCHDPdL n ] complexes were found to be
      microscopically configurationally stable.

PMID- 24115908
TI  - The assessment of science: the relative merits of post-publication review, the
      impact factor, and the number of citations.
AB  - The assessment of scientific publications is an integral part of the scientific
      process. Here we investigate three methods of assessing the merit of a scientific
      paper: subjective post-publication peer review, the number of citations gained by
      a paper, and the impact factor of the journal in which the article was published.
      We investigate these methods using two datasets in which subjective post
      publication assessments of scientific publications have been made by experts. We
      find that there are moderate, but statistically significant, correlations between
      assessor scores, when two assessors have rated the same paper, and between
      assessor score and the number of citations a paper accrues. However, we show that
      assessor score depends strongly on the journal in which the paper is published,
      and that assessors tend to over-rate papers published in journals with high
      impact factors. If we control for this bias, we find that the correlation between
      assessor scores and between assessor score and the number of citations is weak,
      suggesting that scientists have little ability to judge either the intrinsic
      merit of a paper or its likely impact. We also show that the number of citations
      a paper receives is an extremely error-prone measure of scientific merit.
      Finally, we argue that the impact factor is likely to be a poor measure of merit,
      since it depends on subjective assessment. We conclude that the three measures of
      scientific merit considered here are poor; in particular subjective assessments
      are an error-prone, biased, and expensive method by which to assess merit. We
      argue that the impact factor may be the most satisfactory of the methods we have
      considered, since it is a form of pre-publication review. However, we emphasise
      that it is likely to be a very error-prone measure of merit that is qualitative,
      not quantitative. 

PMID- 24115907
TI  - TGF-beta signalling is required for CD4+ T cell homeostasis but dispensable for
      regulatory T cell function.
AB  - TGF-beta is widely held to be critical for the maintenance and function of
      regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by
      constitutive ablation of TGF-beta receptor (TR) during thymic development in
      mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-beta
      driven peripheral tolerance is not regulated by TGF-beta signalling on mature
      CD4+ T cells. Inducible TR2 ablation specifically on CD4+ T cells did not result
      in a lethal autoinflammation. Transfer of these TR2-deficient CD4+ T cells to
      lymphopenic recipients resulted in colitis, but not overt autoimmunity. In
      contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal
      multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4+ T cells
      does not result in the collapse of the T(reg) cell population as observed in
      constitutive models. Instead, a pronounced enlargement of both regulatory and
      effector memory T cell pools was observed. This expansion is cell-intrinsic and
      seems to be caused by increased T cell receptor sensitivity independently of
      common gamma chain-dependent cytokine signals. The expression of Foxp3 and other
      regulatory T cells markers was not dependent on TGF-beta signalling and the TR2
      deficient T(reg) cells retained their suppressive function both in vitro and in
      vivo. In summary, absence of TGF-beta signalling on mature CD4+ T cells is not
      responsible for breakdown of peripheral tolerance, but rather controls
      homeostasis of mature T cells in adult mice.

PMID- 24115910
TI  - Expert failure: re-evaluating research assessment.

PMID- 24115909
TI  - PLZF regulates fibroblast growth factor responsiveness and maintenance of neural
      progenitors.
AB  - Distinct classes of neurons and glial cells in the developing spinal cord arise
      at specific times and in specific quantities from spatially discrete neural
      progenitor domains. Thus, adjacent domains can exhibit marked differences in
      their proliferative potential and timing of differentiation. However, remarkably
      little is known about the mechanisms that account for this regional control.
      Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger
      (PLZF) plays a critical role shaping patterns of neuronal differentiation by
      gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and
      responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression
      and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors
      towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels,
      leading to premature neuronal differentiation. Together, these findings reveal a
      novel transcriptional strategy for spatially tuning the responsiveness of
      distinct neural progenitor groups to broadly distributed mitogenic signals in the
      embryonic environment. 

PMID- 24115911
TI  - Structure of UreG/UreF/UreH complex reveals how urease accessory proteins
      facilitate maturation of Helicobacter pylori urease.
AB  - Urease is a metalloenzyme essential for the survival of Helicobacter pylori in
      acidic gastric environment. Maturation of urease involves carbamylation of Lys219
      and insertion of two nickel ions at its active site. This process requires GTP
      hydrolysis and the formation of a preactivation complex consisting of apo-urease
      and urease accessory proteins UreF, UreH, and UreG. UreF and UreH form a complex
      to recruit UreG, which is a SIMIBI class GTPase, to the preactivation complex. We
      report here the crystal structure of the UreG/UreF/UreH complex, which
      illustrates how UreF and UreH facilitate dimerization of UreG, and assembles its
      metal binding site by juxtaposing two invariant Cys66-Pro67-His68 metal binding
      motif at the interface to form the (UreG/UreF/UreH)2 complex. Interaction studies
      revealed that addition of nickel and GTP to the UreG/UreF/UreH complex releases a
      UreG dimer that binds a nickel ion at the dimeric interface. Substitution of
      Cys66 and His68 with alanine abolishes the formation of the nickel-charged UreG
      dimer. This nickel-charged UreG dimer can activate urease in vitro in the
      presence of the UreF/UreH complex. Static light scattering and atomic absorption
      spectroscopy measurements demonstrated that the nickel-charged UreG dimer, upon
      GTP hydrolysis, reverts to its monomeric form and releases nickel to urease.
      Based on our results, we propose a mechanism on how urease accessory proteins
      facilitate maturation of urease. 

PMID- 24115912
TI  - Completeness of reporting of patient-relevant clinical trial outcomes: comparison
      of unpublished clinical study reports with publicly available data.
AB  - BACKGROUND: Access to unpublished clinical study reports (CSRs) is currently
      being discussed as a means to allow unbiased evaluation of clinical research. The
      Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests
      CSRs from manufacturers for its drug assessments. Our objective was to determine
      the information gain from CSRs compared to publicly available sources (journal
      publications and registry reports) for patient-relevant outcomes included in
      IQWiG health technology assessments (HTAs) of drugs. METHODS AND FINDINGS: We
      used a sample of 101 trials with full CSRs received for 16 HTAs of drugs
      completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the
      CSRs and the publicly available sources of these trials. For each document type
      we assessed the completeness of information on all patient-relevant outcomes
      included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health
      related quality of life; harm outcomes, e.g., adverse events). We dichotomized
      the outcomes as "completely reported" or "incompletely reported." For each
      document type, we calculated the proportion of outcomes with complete information
      per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at
      least one publicly available source, 65 at least one journal publication, and 50
      a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs
      provided complete information on a considerably higher proportion of outcomes
      (86%) than the combined publicly available sources (39%). With the exception of
      health-related quality of life (57%), CSRs provided complete information on 78%
      to 100% of the various benefit outcomes (combined publicly available sources: 20%
      to 53%). CSRs also provided considerably more information on harms. The
      differences in completeness of information for patient-relevant outcomes between
      CSRs and journal publications or registry reports (or a combination of both) were
      statistically significant for all types of outcomes. The main limitation of our
      study is that our sample is not representative because only CSRs provided
      voluntarily by pharmaceutical companies upon request could be assessed. In
      addition, the sample covered only a limited number of therapeutic areas and was
      restricted to randomized controlled trials investigating drugs. CONCLUSIONS: In
      contrast to CSRs, publicly available sources provide insufficient information on
      patient-relevant outcomes of clinical trials. CSRs should therefore be made
      publicly available. Please see later in the article for the Editors' Summary.

PMID- 24115913
TI  - Assessing optimal target populations for influenza vaccination programmes: an
      evidence synthesis and modelling study.
AB  - BACKGROUND: Influenza vaccine policies that maximise health benefit through
      efficient use of limited resources are needed. Generally, influenza vaccination
      programmes have targeted individuals 65 y and over and those at risk, according
      to World Health Organization recommendations. We developed methods to synthesise
      the multiplicity of surveillance datasets in order to evaluate how changing
      target populations in the seasonal vaccination programme would affect infection
      rate and mortality. METHODS AND FINDINGS: Using a contemporary evidence-synthesis
      approach, we use virological, clinical, epidemiological, and behavioural data to
      develop an age- and risk-stratified transmission model that reproduces the strain
      specific behaviour of influenza over 14 seasons in England and Wales, having
      accounted for the vaccination uptake over this period. We estimate the reduction
      in infections and deaths achieved by the historical programme compared with no
      vaccination, and the reduction had different policies been in place over the
      period. We find that the current programme has averted 0.39 (95% credible
      interval 0.34-0.45) infections per dose of vaccine and 1.74 (1.16-3.02) deaths
      per 1,000 doses. Targeting transmitters by extending the current programme to 5
      16-y-old children would increase the efficiency of the total programme, resulting
      in an overall reduction of 0.70 (0.52-0.81) infections per dose and 1.95 (1.28
      3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk
      (50-64-y-olds) would prevent only 0.43 (0.35-0.52) infections per dose and 1.77
      (1.15-3.14) deaths per 1,000 doses. CONCLUSIONS: This study proposes a framework
      to integrate influenza surveillance data into transmission models. Application to
      data from England and Wales confirms the role of children as key infection
      spreaders. The most efficient use of vaccine to reduce overall influenza
      morbidity and mortality is thus to target children in addition to older adults.
      Please see later in the article for the Editors' Summary.

PMID- 24115914
TI  - Why we must provide better support for Pakistan's female frontline health
      workers.
AB  - Svea Closser and Rashid Jooma argue that achieving polio eradication and
      strengthening Pakistan's health system must focus not just on international
      engagement but also on local partnerships with Lady Health Workers and other
      ground-level staff. Please see later in the article for the Editors' Summary. 

PMID- 24115915
TI  - The final push for polio eradication: addressing the challenge of violence in
      Afghanistan, Pakistan, and Nigeria.
AB  - Seye Abimbola and colleagues provide a view from Nigeria, Pakistan, and
      Afghanistan on global efforts to eradicate polio in those countries. Please see
      later in the article for the Editors' Summary. 

PMID- 24115917
TI  - Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the
      treatment of HER-2-overexpressing locally advanced or metastatic breast cancer:
      systematic review and meta-analysis.
AB  - BACKGROUND: This paper reports a systematic review and meta-analysis of all
      randomized controlled trials comparing the efficacy of lapatinib plus
      chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal
      growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic
      breast cancer. METHODS: Several databases were searched, including MEDLINE,
      EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival
      and overall survival. The side effects of each treatment were analyzed. The data
      extracted from the studies were combined by using the hazard ratio or risk ratio
      with their corresponding 95% confidence interval (CI). RESULTS: A total of 113
      references were identified and screened. The final analysis included four trials
      comprising 1,073 patients with HER-2+. The overall response rate was higher in
      patients who received the combination of CET plus lapatinib (risk ratio 0.78; 95%
      CI 0.71-0.85; P < 0.00001) but with significant heterogeneity (chi(2) = 15.61, df
      = 3; P = 0.001; I(2) = 81%). This result remained favorable to the use of
      lapatinib when a random-effects model analysis was performed (risk ratio 0.76;
      95% CI 0.62-0.94; P = 0.01). Progression-free survival was also higher in
      patients who received CET plus lapatinib (hazard ratio 0.57; 95% CI 0.49-0.66; P
      < 0.00001) with no heterogeneity detected on this analysis (chi(2) = 3.05; df =
      3; P = 0.38; I(2) = 1%). Overall survival was significantly longer in patients
      who received CET plus lapatinib (hazard ratio 0.80; 95% CI 0.69-0.92; P = 0.002)
      without heterogeneity on this analysis (chi(2) = 1.26; df = 3; P = 0.74; I(2) =
      0%). Regarding adverse events and severe toxicities (grade >=3), the group
      receiving CET plus lapatinib had higher rates of neutropenia (risk ratio 2.08;
      95% CI 1.64-2.62; P < 0.00001), diarrhea (risk ratio 4.82; 95% CI 3.14-7.41; P <
      0.00001), and rash (risk ratio 8.03; 95% CI 2.46-26.23; P = 0.0006). CONCLUSION:
      The combination of CET plus lapatinib increased the overall response rate,
      progression-free survival, and overall survival in patients with HER-2+ locally
      advanced or metastatic breast cancer.

PMID- 24115918
TI  - Mothers' amygdala response to positive or negative infant affect is modulated by
      personal relevance.
AB  - Understanding, prioritizing and responding to infant affective cues is a key
      component of motherhood, with long-term implications for infant socio-emotional
      development. This important task includes identifying unique characteristics of
      one's own infant, as they relate to differences in affect valence-happy or sad
      while monitoring one's own level of arousal. The amygdala has traditionally been
      understood to respond to affective valence; in the present study, we examined the
      potential effect of personal relevance on amygdala response, by testing whether
      mothers' amygdala response to happy and sad infant face cues would be modulated
      by infant identity. We used functional MRI to measure amygdala activation in 39
      first-time mothers, while they viewed happy, neutral and sad infant faces of both
      their own and a matched unknown infant. Emotional arousal to each face was rated
      using the Self-Assessment Manikin Scales. Mixed-effects linear regression models
      were used to examine significant predictors of amygdala response. Overall, both
      arousal ratings and amygdala activation were greater when mothers viewed their
      own infant's face compared with unknown infant faces. Sad faces were rated as
      more arousing than happy faces, regardless of infant identity. However, within
      the amygdala, a highly significant interaction effect was noted between infant
      identity and valence. For own-infant faces, amygdala activation was greater for
      happy than sad faces, whereas the opposite trend was seen for unknown-infant
      faces. Our findings suggest that the amygdala response to positive or negative
      valenced cues is modulated by personal relevance. Positive facial expressions
      from one's own infant may play a particularly important role in eliciting
      maternal responses and strengthening the mother-infant bond. 

PMID- 24115919
TI  - Real-time classification and sensor fusion with a spiking deep belief network.
AB  - Deep Belief Networks (DBNs) have recently shown impressive performance on a broad
      range of classification problems. Their generative properties allow better
      understanding of the performance, and provide a simpler solution for sensor
      fusion tasks. However, because of their inherent need for feedback and parallel
      update of large numbers of units, DBNs are expensive to implement on serial
      computers. This paper proposes a method based on the Siegert approximation for
      Integrate-and-Fire neurons to map an offline-trained DBN onto an efficient event
      driven spiking neural network suitable for hardware implementation. The method is
      demonstrated in simulation and by a real-time implementation of a 3-layer network
      with 2694 neurons used for visual classification of MNIST handwritten digits with
      input from a 128 * 128 Dynamic Vision Sensor (DVS) silicon retina, and sensory
      fusion using additional input from a 64-channel AER-EAR silicon cochlea. The
      system is implemented through the open-source software in the jAER project and
      runs in real-time on a laptop computer. It is demonstrated that the system can
      recognize digits in the presence of distractions, noise, scaling, translation and
      rotation, and that the degradation of recognition performance by using an event
      based approach is less than 1%. Recognition is achieved in an average of 5.8 ms
      after the onset of the presentation of a digit. By cue integration from both
      silicon retina and cochlea outputs we show that the system can be biased to
      select the correct digit from otherwise ambiguous input. 

PMID- 24115920
TI  - A new role for P2X4 receptors as modulators of lung surfactant secretion.
AB  - In recent years, P2X receptors have attracted increasing attention as regulators
      of exocytosis and cellular secretion. In various cell types, P2X receptors have
      been found to stimulate vesicle exocytosis directly via Ca(2+) influx and
      elevation of the intracellular Ca(2+) concentration. Recently, a new role for
      P2X4 receptors as regulators of secretion emerged. Exocytosis of lamellar bodies
      (LBs), large storage organelles for lung surfactant, results in a local, fusion
      activated Ca(2+) entry (FACE) in alveolar type II epithelial cells. FACE is
      mediated via P2X4 receptors that are located on the limiting membrane of LBs and
      inserted into the plasma membrane upon exocytosis of LBs. The localized Ca(2+)
      influx at the site of vesicle fusion promotes fusion pore expansion and
      facilitates surfactant release. In addition, this inward-rectifying cation
      current across P2X4 receptors mediates fluid resorption from lung alveoli. It is
      hypothesized that the concomitant reduction in the alveolar lining fluid
      facilitates insertion of surfactant into the air-liquid interphase thereby
      "activating" it. These findings constitute a novel role for P2X4 receptors in
      regulating vesicle content secretion as modulators of the secretory output during
      the exocytic post-fusion phase. 

PMID- 24115921
TI  - Cerebellar cortical neuron responses evoked from the spinal border cell tract.
AB  - Spinocerebellar systems are likely to be crucial for cerebellar hallmark
      functions such as coordination. However, in terms of cerebellar functional
      analyses, these are perhaps among the least explored systems. The aim of the
      present study is to achieve activation of a single component of the
      spinocerebellar systems and to explore to what extent it can influence the spike
      output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate
      and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage
      of a unique arrangement discovered in neuroanatomical studies, in which the
      spinal border cell (SBC) component of the ventral spinocerebellar system was
      found to be the only spinocerebellar tract which ascends in the contralateral
      lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian
      lobule in the posterior cerebellum. Using electrical stimulation of this tract,
      we find a subset of the cerebellar cortical neurons in this region to be
      moderately or powerfully activated. For example, some of our granule cells
      displayed high intensity responses whereas the majority of the granule cells
      displayed no response at all. The finding that more than half of the PCs were
      activated by stimulation of the SBC tract indicated that this system is capable
      of directly influencing cerebellar cortical output. The implications of these
      findings for the view of the integrative functions of the cerebellar cortex are
      discussed. 

PMID- 24115922
TI  - In vivo monitoring of chemically evoked activity patterns in the rat trigeminal
      ganglion.
AB  - Albeit lacking a sense of smell, anosmic patients maintain a reduced ability to
      distinguish different volatile chemicals by relying exclusively on their
      trigeminal system (TS). To elucidate differences in the neuronal representation
      of these volatile substances in the TS, we performed voltage-sensitive dye
      imaging (VSDI) in the rat trigeminal ganglion (TG) in vivo. We demonstrated that
      stimulus-specific patterns of bioelectrical activity occur within the TG upon
      nasal administration of ten different volatile chemicals. With regard to spatial
      differences between the evoked trigeminal response patterns, these substances
      could be sorted into three groups. Signal intensity and onset latencies were also
      dependent on the administered stimulus and its concentration. We conclude that
      particular compounds detected by the TS are represented by (1) a specific spatial
      response pattern, (2) the signal intensity, and (3) onset latencies within the
      pattern. Jointly, these trigeminal representations may contribute to the
      surprisingly high discriminative skills of anosmic patients. 

PMID- 24115923
TI  - The influence of prior knowledge on memory: a developmental cognitive
      neuroscience perspective.
AB  - Across ontogenetic development, individuals gather manifold experiences during
      which they detect regularities in their environment and thereby accumulate
      knowledge. This knowledge is used to guide behavior, make predictions, and
      acquire further new knowledge. In this review, we discuss the influence of prior
      knowledge on memory from both the psychology and the emerging cognitive
      neuroscience literature and provide a developmental perspective on this topic.
      Recent neuroscience findings point to a prominent role of the medial prefrontal
      cortex (mPFC) and of the hippocampus (HC) in the emergence of prior knowledge and
      in its application during the processes of successful memory encoding,
      consolidation, and retrieval. We take the lateral PFC into consideration as well
      and discuss changes in both medial and lateral PFC and HC across development and
      postulate how these may be related to the development of the use of prior
      knowledge for remembering. For future direction, we argue that, to measure age
      differential effects of prior knowledge on memory, it is necessary to distinguish
      the availability of prior knowledge from its accessibility and use. 

PMID- 24115924
TI  - Post-perceptual processing during the attentional blink is modulated by inter
      trial task expectancies.
AB  - The selective processing of goal-relevant information depends on an attention
      system that can flexibly adapt to changing task demands and expectations.
      Evidence from visual search tasks indicates that the perceptual selectivity of
      attention increases when the bottom-up demands of the task increase and when the
      expectations about task demands engendered by trial history are violated.
      Evidence from studies of the attentional blink (AB), which measures the temporal
      dynamics of attention, also indicates that perceptual selectivity during the AB
      is increased if the bottom-up task demands are increased. The present work tested
      whether expectations about task demands engendered by trial history also modulate
      perceptual selectivity during the AB. Two experiments tested the extent to which
      inter-trial switches in task demands reduced post-perceptual processing of
      targets presented during the AB. Experiment 1 indexed post-perceptual processing
      using the event-related potential (ERP) technique to isolate the context
      sensitive N400 ERP component evoked by words presented during the AB. Experiment
      2 indexed post-perceptual processing using behavioral performance to determine
      the extent to which personal names survive the AB. The results of both
      experiments revealed that both electrophysiological (Exp. 1) and behavioral (Exp.
      2) indices of post-perceptual processing were attenuated when consecutive trials
      differed in terms of their perceptual demands. The results are consistent with
      the notion that the selectivity of attention during the AB is modulated not only
      by within-trial task demands, but also can be flexibly determined by trial-by
      trial expectations. 

PMID- 24115925
TI  - How you perceive threat determines your behavior.
AB  - The prioritization of processing emotional stimuli usually produces deleterious
      effects on task performance when it distracts from a task. One common explanation
      is that brain resources are consumed by emotional stimuli, diverting resources
      away from executing the task. Viewing unpleasant stimuli also generates defensive
      reactions, and these responses may be at least partially responsible for the
      effect of the emotional modulation observed in various reaction time (RT)
      paradigms. We investigated whether modulatory effects on RT vary if we presented
      threat stimuli to prompt different defensive responses. To trigger different
      responses, we manipulated threat perception by moving the direction of
      threatening stimuli. Threatening or neutral stimuli were presented as distractors
      during a bar orientation discrimination task. The results demonstrated that
      threat stimuli directed toward the observer produced a decrease in RT; in
      contrast, threat stimuli directed away from the observer produced an increase in
      RT, when compared to neutral stimuli. Accelerated RT during directed toward
      threat stimuli was attributed to increased motor preparation resulting from
      strong activation of the defense response cascade. In contrast, directed away
      threat stimuli likely activated the defense cascade, but less intensively,
      prompting immobility. Different threat stimuli produced varying effects, which
      was interpreted as evidence that the modulation of RT by emotional stimuli
      represents the summation of attentional and motivational effects. Additionally,
      participants who had been previously exposed to diverse types of violent crime
      were more strongly influenced by threat stimuli directed toward the observer. In
      sum, our data support the concept that emotions are indeed action tendencies. 

PMID- 24115926
TI  - Anxiety and error monitoring: the importance of motivation and emotion.

PMID- 24115927
TI  - Task decomposition: a framework for comparing diverse training models in human
      brain plasticity studies.
AB  - Training studies, in which the structural or functional neurophysiology is
      compared before and after expertise is acquired, are increasingly being used as
      models for understanding the human brain's potential for reorganization. It is
      proving difficult to use these results to answer basic and important questions
      like how task training leads to both specific and general changes in behavior and
      how these changes correspond with modifications in the brain. The main culprit is
      the diversity of paradigms used as complex task models. An assortment of
      activities ranging from juggling to deciphering Morse code has been reported.
      Even when working in the same general domain, few researchers use similar
      training models. New ways to meaningfully compare complex tasks are needed. We
      propose a method for characterizing and deconstructing the task requirements of
      complex training paradigms, which is suitable for application to both structural
      and functional neuroimaging studies. We believe this approach will aid brain
      plasticity research by making it easier to compare training paradigms, identify
      "missing puzzle pieces," and encourage researchers to design training protocols
      to bridge these gaps. 

PMID- 24115928
TI  - Old cortex, new contexts: re-purposing spatial perception for social cognition.
AB  - Much of everyday mental life involves information that we cannot currently
      perceive directly, from contemplating the strengths of friendships to reasoning
      about the contents of other minds. Despite their primacy to everyday human
      functioning, and in particular, to human sociality, the mechanisms that support
      abstract thought are poorly understood. An explanatory framework that has gained
      traction recently in cognitive neuroscience is exaptation, or the re-purposing of
      evolutionarily old circuitry to carry out new functions. We argue for the utility
      of applying this concept to social cognition. Convergent behavioral and
      neuroscientific evidence suggests that humans co-opt mechanisms originally
      devoted to spatial perception for more abstract domains of cognition (e.g.,
      temporal reasoning). Preliminary evidence suggests that some aspects of social
      cognition also involve the exaptation of substrates originally evolved for
      processing physical space. We discuss the potential for future work to test more
      directly if cortical substrates for spatial processing were exapted for social
      cognition, and in so doing, to improve our understanding of how humans evolved
      mechanisms for navigating an exceptionally complex social world. 

PMID- 24115929
TI  - On development of functional brain connectivity in the young brain.
AB  - Our brain is a complex network of structurally and functionally interconnected
      regions, shaped to efficiently process and integrate information. The development
      from a brain equipped with basic functionalities to an efficient network
      facilitating complex behavior starts during gestation and continues into
      adulthood. Resting-state functional MRI (rs-fMRI) enables the examination of
      developmental aspects of functional connectivity (FC) and functional brain
      networks. This review will discuss changes observed in the developing brain on
      the level of network FC from a gestational age of 20 weeks onwards. We discuss
      findings of resting-state fMRI studies showing that functional network
      development starts during gestation, creating a foundation for each of the
      resting-state networks (RSNs) to be established. Visual and sensorimotor areas
      are reported to develop first, with other networks, at different rates,
      increasing both in network connectivity and size over time. Reaching childhood,
      marked fine-tuning and specialization takes place in the regions necessary for
      higher-order cognitive functions. 

PMID- 24115930
TI  - A review of visual perspective taking in autism spectrum disorder.
AB  - Impairments in social cognition are a key symptom of autism spectrum disorder
      (ASD). People with autism have great difficulty with understanding the beliefs
      and desires of other people. In recent years literature has begun to examine the
      link between impairments in social cognition and abilities which demand the use
      of spatial and social skills, such as visual perspective taking (VPT). Flavell
      (1977) defined two levels of perspective taking: VPT level 1 is the ability to
      understand that other people have a different line of sight to ourselves, whereas
      VPT level 2 is the understanding that two people viewing the same item from
      different points in space may see different things. So far, literature on whether
      either level of VPT is impaired or intact in autism is inconsistent. Here we
      review studies which have examined VPT levels 1 and 2 in people with autism with
      a focus on their methods. We conclude the review with an evaluation of the
      findings into VPT in autism and give recommendations for future research which
      may give a clearer insight into whether perspective taking is truly impaired in
      autism. 

PMID- 24115931
TI  - From self-assessment to frustration, a small step toward autonomy in robotic
      navigation.
AB  - Autonomy and self-improvement capabilities are still challenging in the fields of
      robotics and machine learning. Allowing a robot to autonomously navigate in wide
      and unknown environments not only requires a repertoire of robust strategies to
      cope with miscellaneous situations, but also needs mechanisms of self-assessment
      for guiding learning and for monitoring strategies. Monitoring strategies
      requires feedbacks on the behavior's quality, from a given fitness system in
      order to take correct decisions. In this work, we focus on how a second-order
      controller can be used to (1) manage behaviors according to the situation and (2)
      seek for human interactions to improve skills. Following an incremental and
      constructivist approach, we present a generic neural architecture, based on an on
      line novelty detection algorithm that may be able to self-evaluate any sensory
      motor strategies. This architecture learns contingencies between sensations and
      actions, giving the expected sensation from the previous perception. Prediction
      error, coming from surprising events, provides a measure of the quality of the
      underlying sensory-motor contingencies. We show how a simple second-order
      controller (emotional system) based on the prediction progress allows the system
      to regulate its behavior to solve complex navigation tasks and also succeeds in
      asking for help if it detects dead-lock situations. We propose that this model
      could be a key structure toward self-assessment and autonomy. We made several
      experiments that can account for such properties for two different strategies
      (road following and place cells based navigation) in different situations. 

PMID- 24115932
TI  - The role of auditory abilities in basic mechanisms of cognition in older adults.
AB  - The aim of this study was to assess age-related differences between young and
      older adults in auditory abilities and to investigate the relationship between
      auditory abilities and basic mechanisms of cognition in older adults. Although
      there is a certain consensus that the participant's sensitivity to the absolute
      intensity of sounds (such as that measured via pure tone audiometry) explains
      his/her cognitive performance, there is not yet much evidence that the
      participant's auditory ability (i.e., the whole supra-threshold processing of
      sounds) explains his/her cognitive performance. Twenty-eight young adults (age
      <35), 26 young-old adults (65 i age i 75), and 28 old-old adults (age >75) were
      presented with a set of tasks estimating several auditory abilities (i.e.,
      frequency discrimination, intensity discrimination, duration discrimination,
      timbre discrimination, gap detection, amplitude modulation detection, and the
      absolute threshold for a 1 kHz pure tone) and the participant's working memory,
      cognitive inhibition, and processing speed. Results showed an age-related decline
      in both auditory and cognitive performance. Moreover, regression analyses showed
      that a subset of the auditory abilities (i.e., the ability to discriminate
      frequency, duration, timbre, and the ability to detect amplitude modulation)
      explained a significant part of the variance observed in the processing speed of
      older adults. Overall, the present results highlight the relationship between
      auditory abilities and basic mechanisms of cognition. 

PMID- 24115933
TI  - Anti-cancer activities of pH- or heat-modified pectin.
AB  - Despite enormous efforts that have been made in the search for novel drugs and
      treatments, cancer continues to be a major public health problem. Moreover, the
      emergence of resistance to cancer chemotherapy often prevents complete remission.
      Researchers have thus turned to natural products mainly from plant origin to
      circumvent resistance. Pectin and pH- or heat-modified pectin have demonstrated
      chemopreventive and antitumoral activities against some aggressive and recurrent
      cancers. The focus of this review is to describe how pectin and modified pectin
      display these activities and what are the possible underlying mechanisms. The
      failure of conventional chemotherapy to reduce mortality as well as serious side
      effects make natural products, such as pectin-derived products, ideal candidates
      for exerting synergism in combination with conventional anticancer drugs. 

PMID- 24115934
TI  - Electrophysiological and structural determinants of electrotonic modulation of
      repolarization by the activation sequence.
AB  - Spatial dispersion of repolarization is known to play an important role in
      arrhythmogenesis. Electrotonic modulation of repolarization by the activation
      sequence has been observed in some species and tissue preparations, but to
      varying extents. Our study sought to determine the mechanisms underlying species-
      and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi
      fluorescence optical imaging of whole rat hearts and pig left ventricular wedges
      were used to assess epicardial spatial activation and repolarization
      characteristics. Experiments were supported by computer simulations using
      realistic geometries. Tight coupling between activation times (AT) and action
      potential duration (APD) were observed in rat experiments but not in pig. Linear
      correlation analysis found slopes of -1.03 +/- 0.59 and -0.26 +/- 0.13 for rat
      and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 +/
      3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous
      (8.2 +/- 2.7, p < 0.0001). However, in pig no such difference was observed
      between the dispersion of APD and RT (17.8 +/- 6.1 vs. 17.7 +/- 6.5,
      respectively). Localized elevations of APD (12.9 +/- 8.3%) were identified at
      ventricular insertion sites of rat hearts both in experiments and simulations.
      Tissue geometry and action potential (AP) morphology contributed significantly to
      determining influence of electrotonic modulation. Simulations of a rat AP in a
      pig geometry decreased the slope of AT and APD relationships by 70.6% whereas
      slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A
      modified pig AP, shortened to match the rat APD, showed little coupling between
      AT and APD with greatly reduced slope compared to the rat AP. Electrotonic
      modulation of repolarization by the activation sequence is especially pronounced
      in small hearts with murine-like APs. Tissue architecture and AP morphology play
      an important role in electrotonic modulation of repolarization. 

PMID- 24115936
TI  - The shame of addiction.
AB  - Addiction is a person-level phenomenon that involves twin normative failures. A
      failure of normal rational effective agency or self-control with respect to the
      substance; and shame at both this failure, and the failure to live up to the
      standards for a good life that the addict himself acknowledges and aspires to.
      Feeling shame for addiction is not a mistake. It is part of the shape of
      addiction, part of the normal phenomenology of addiction, and often a source of
      motivation for the addict to heal. Like other recent attempts in the addiction
      literature to return normative concepts such as "choice" and "responsibility" to
      their rightful place in understanding and treating addiction, the twin normative
      failure model is fully compatible with investigation of genetic and
      neuroscientific causes of addiction. Furthermore, the model does not re-moralize
      addiction. There can be shame without blame. 

PMID- 24115935
TI  - Emerging role of the endoplasmic reticulum in peroxisome biogenesis.
AB  - During the past few years, we have witnessed a paradigm shift in our long
      standing concept of peroxisome biogenesis. Recent biochemical and morphological
      studies have revealed a primary role of the endoplasmic reticulum (ER) in the de
      novo formation of peroxisomes, thus challenging the prevalent model invoking
      growth and division of pre-existing peroxisomes. Importantly, a novel sorting
      process has been recently defined at the ER that segregates and assembles
      specific sets of peroxisomal membrane proteins (PMPs) into distinct pre
      peroxisomal vesicular carriers (ppVs) that later undergo heterotypic fusion to
      form mature peroxisomes. Consequently, the emerging model has redefined the
      function of many peroxins (most notably Pex3, Pex19, and Pex25) and assigned them
      novel roles in vesicular budding and subsequent peroxisome assembly. These
      advances establish a novel intracellular membrane trafficking route between the
      ER and peroxisomes, but the components remain elusive. This review will provide a
      historical perspective and focus on recent developments in the emerging role of
      the ER in peroxisome biogenesis. 

PMID- 24115937
TI  - Verbal memory functioning in recurrent depression during partial remission and
      remission-Brief report.
AB  - The aim of the present study was to investigate verbal memory performance in a
      group of patients with remitted and partial remitted major depressive disorder.
      Thirty-one patients and 31 healthy matched controls were included in the study.
      Results from the California Verbal Learning Test show intact verbal memory
      performance in the patient group regarding learning, recall and recognition.
      However, patients had significantly poorer performance compared to healthy
      controls in immediate recall of the first trial in the verbal memory test. In
      conclusion, the patient group showed intact memory performance, when material is
      presented more than once. These findings indicate that memory performance in MDD
      patients with partial remission and remission benefit from repetition of
      material. 

PMID- 24115938
TI  - Bodily pleasure matters: velocity of touch modulates body ownership during the
      rubber hand illusion.
AB  - The sense of body ownership represents a fundamental aspect of our self
      consciousness. Influential experimental paradigms, such as the rubber hand
      illusion (RHI), in which a seen rubber hand is experienced as part of one's body
      when one's own unseen hand receives congruent tactile stimulation, have
      extensively examined the role of exteroceptive, multisensory integration on body
      ownership. However, remarkably, despite the more general current interest in the
      nature and role of interoception in emotion and consciousness, no study has
      investigated how the illusion may be affected by interoceptive bodily signals,
      such as affective touch. Here, we recruited 52 healthy, adult participants and we
      investigated for the first time, whether applying slow velocity, light tactile
      stimuli, known to elicit interoceptive feelings of pleasantness, would influence
      the illusion more than faster, emotionally-neutral, tactile stimuli. We also
      examined whether seeing another person's hand vs. a rubber hand would reduce the
      illusion in slow vs. fast stroking conditions, as interoceptive signals are used
      to represent one's own body from within and it is unclear how they would be
      integrated with visual signals from another person's hand. We found that slow
      velocity touch was perceived as more pleasant and it produced higher levels of
      subjective embodiment during the RHI compared with fast touch. Moreover, this
      effect applied irrespective of whether the seen hand was a rubber or a
      confederate's hand. These findings provide support for the idea that affective
      touch, and more generally interoception, may have a unique contribution to the
      sense of body ownership, and by implication to our embodied psychological "self."

PMID- 24115939
TI  - Interactional convergence in conversational storytelling: when reported speech is
      a cue of alignment and/or affiliation.
AB  - This paper investigates how and when interactional convergence is established by
      participants in conversation. We analyze sequences of storytelling using an
      original method that combines Conversation Analysis and a corpus-based approach.
      In storytelling, the participant in the position of "listener" is expected to
      produce either generic or specific responses adapted to the storyteller's
      narrative. The listener's behavior produced within the current activity is a cue
      of his/her interactional alignment. We show here that the listener can produce a
      specific type of (aligned) response, which we term a reported speech utterance in
      echo. The participant who is not telling the story is nonetheless able to animate
      the characters, while reversing the usual asymmetric roles of storyteller and
      listener. The use of this device is a way for the listener to display his/her
      stance toward the events told by the storyteller. If the listener's stance is
      congruent with that of the storyteller, this reveals a high degree of affiliation
      between the participants. We present seventeen excerpts from a collection of 94
      instances of Echo Reported Speech (ERS) which we examined using the concepts of
      alignment and affiliation in order to show how different kinds of convergent
      sequences are constructed. We demonstrate that this phenomenon is mainly used by
      the listener to align and affiliate with the storyteller by means of
      reformulative, enumerative, or overbidding ERS. We also show that in affiliative
      sequences, reported speech can be used by the listener in a humorous way in order
      to temporarily disalign. This disalignment constitutes a potential starting point
      for an oblique sequence, which, if accepted and continued by the storyteller,
      gives rise to a highly convergent sequence. 

PMID- 24115940
TI  - Afterimage watercolors: an exploration of contour-based afterimage filling-in.
AB  - We investigated filling-in of colored afterimages and compared them with filling
      in of "real" colors in the watercolor illusion. We used shapes comprising two
      thin adjacent undulating outlines of which the inner or the outer outline was
      chromatic, while the other was achromatic. The outlines could be presented
      simultaneously, inducing the original watercolor effect, or in an alternating
      fashion, inducing colored afterimages of the chromatic outlines. In Experiment 1,
      using only alternating outlines, these afterimages triggered filling-in,
      revealing an "afterimage watercolor" effect. Depending on whether the inner or
      the outer outline was chromatic, filling-in of a complementary or a similarly
      colored afterimage was perceived. In Experiment 2, simultaneous and alternating
      presentations were compared. Additionally, gray and black achromatic contours
      were tested, having an increased luminance contrast with the background for the
      black contours. Compared to "real" color filling-in, afterimage filling-in was
      more easily affected by different luminance settings. More in particular,
      afterimage filling-in was diminished when high-contrast contours were used. In
      the discussion we use additional demonstrations in which we further explore the
      "watercolor afterimage." All in all, comparisons between both types of illusions
      show similarities and differences with regard to color filling-in. Caution,
      however, is warranted in attributing these effects to different underlying
      processing differences. 

PMID- 24115942
TI  - Erratum: Genetic modulation of training and transfer in older adults: BDNF
      Val66Met polymorphism is associated with wider useful field of view.
AB  - [This corrects the article on p. 199 in vol. 2, PMID: 21909331.].

PMID- 24115941
TI  - The Iowa Gambling Task and the three fallacies of dopamine in gambling disorder.
AB  - Gambling disorder sufferers prefer immediately larger rewards despite long term
      losses on the Iowa Gambling Task (IGT), and these impairments are associated with
      dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and
      structural dysfunctions in substance use disorder, which has supported the idea
      of impaired decision-making and dopamine dysfunctions in gambling disorder.
      However, evidence from substance use disorders cannot be directly transferred to
      gambling disorder. This article focuses on three hypotheses of dopamine
      dysfunctions in gambling disorder, which appear to be "fallacies," i.e., have not
      been supported in a series of positron emission tomography (PET) studies. The
      first "fallacy" suggests that gambling disorder sufferers have lower dopamine
      receptor availability, as seen in substance use disorders. However, no evidence
      supported this hypothesis. The second "fallacy" suggests that maladaptive
      decision-making in gambling disorder is associated with higher dopamine release
      during gambling. No evidence supported the hypothesis, and the literature on
      substance use disorders offers limited support for this hypothesis. The third
      "fallacy" suggests that maladaptive decision-making in gambling disorder is
      associated with higher dopamine release during winning. The evidence did not
      support this hypothesis either. Instead, dopaminergic coding of reward prediction
      and uncertainty might better account for dopamine dysfunctions in gambling
      disorder. Studies of reward prediction and reward uncertainty show a sustained
      dopamine response toward stimuli with maximum uncertainty, which may explain the
      continued dopamine release and gambling despite losses in gambling disorder. The
      findings from the studies presented here are consistent with the notion of
      dopaminergic dysfunctions of reward prediction and reward uncertainty signals in
      gambling disorder. 

PMID- 24115943
TI  - Narcolepsy or Sleep Apnea?: Not Everything is What it Appears to be!

PMID- 24115944
TI  - Quantitative in silico Analysis of Neurotransmitter Pathways Under Steady State
      Conditions.
AB  - The modeling of glutamate/GABA-glutamine cycling in the brain tissue involving
      astrocytes, glutamatergic and GABAergic neurons leads to a complex
      compartmentalized metabolic network that comprises neurotransmitter synthesis,
      shuttling, and degradation. Without advanced computational tools, it is difficult
      to quantitatively track possible scenarios and identify viable ones. In this
      article, we follow a sampling-based computational paradigm to analyze the
      biochemical network in a multi-compartment system modeling astrocytes,
      glutamatergic, and GABAergic neurons, and address some questions about the
      details of transmitter cycling, with particular emphasis on the ammonia shuttling
      between astrocytes and neurons, and the synthesis of transmitter GABA. More
      specifically, we consider the joint action of the alanine-lactate shuttle, the
      branched chain amino acid shuttle, and the glutamine-glutamate cycle, as well as
      the role of glutamate dehydrogenase (GDH) activity. When imposing a minimal
      amount of bound constraints on reaction and transport fluxes, a preferred
      stoichiometric steady state equilibrium requires an unrealistically high
      reductive GDH activity in neurons, indicating the need for additional bound
      constants which were included in subsequent computer simulations. The statistical
      flux balance analysis also suggests a stoichiometrically viable role for leucine
      transport as an alternative to glutamine for replenishing the glutamate pool in
      neurons. 

PMID- 24115945
TI  - Grand challenges in cancer endocrinology: endocrine related cancers, an expanding
      concept.

PMID- 24115946
TI  - Update on antibiotic resistance in foodborne Lactobacillus and Lactococcus
      species.
AB  - Lactobacilli represent a major Lactic Acid Bacteria (LAB) component within the
      complex microbiota of fermented foods obtained from meat, dairy, and vegetable
      sources. Lactococci, on the other hand, are typical of milk and fermented dairy
      products, which in turn represent the vast majority of fermented foods. As is the
      case for all species originating from the environment, foodborne lactobacilli and
      lactococci consist of natural, uncharacterized strains, whose biodiversity
      depends on geographical origin, seasonality, animal feeding/plant growth
      conditions. Although a few species of opportunistic pathogens have been
      described, lactobacilli and lactococci are mostly non-pathogenic, Gram-positive
      bacteria displaying probiotic features. Since antibiotic resistant (AR) strains
      do not constitute an immediate threat to human health, scientific interest for
      detailed studies on AR genes in these species has been greatly hindered. However,
      increasing evidence points at a crucial role for foodborne LAB as reservoir of
      potentially transmissible AR genes, underlining the need for further, more
      detailed studies aimed at identifying possible strategies to avoid AR spread to
      pathogens through fermented food consumption. The availability of a growing
      number of sequenced bacterial genomes has been very helpful in identifying the
      presence/distribution of mobile elements associated with AR genes, but open
      questions and knowledge gaps still need to be filled, highlighting the need for
      systematic and datasharing approaches to implement both surveillance and
      mechanistic studies on transferability of AR genes. In the present review we
      report an update of the recent literature on AR in lactobacilli and lactococci
      following the 2006 EU-wide ban of the use of antibiotics as feed additives in
      animal farming, and we discuss the limits of the present knowledge in evaluating
      possible risks for human health. 

PMID- 24115947
TI  - Interleukin-18 and IL-18 binding protein.
AB  - Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL
      1beta, IL-18 is synthesized as an inactive precursor requiring processing by
      caspase-1 into an active cytokine but unlike IL-1beta, the IL-18 precursor is
      constitutively present in nearly all cells in healthy humans and animals. The
      activity of IL-18 is balanced by the presence of a high affinity, naturally
      occurring IL-18 binding protein (IL-18BP). In humans, increased disease severity
      can be associated with an imbalance of IL-18 to IL-18BP such that the levels of
      free IL-18 are elevated in the circulation. Increasing number of studies have
      expanded the role of IL-18 in mediating inflammation in animal models of disease
      using the IL-18BP, IL-18-deficient mice, neutralization of IL-18, or deficiency
      in the IL-18 receptor alpha chain. A role for IL-18 has been implicated in
      several autoimmune diseases, myocardial function, emphysema, metabolic syndromes,
      psoriasis, inflammatory bowel disease, hemophagocytic syndromes, macrophage
      activation syndrome, sepsis, and acute kidney injury, although in some models of
      disease, IL-18 is protective. IL-18 plays a major role in the production of
      interferon-gamma from T-cells and natural killer cells. The IL-18BP has been used
      safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL
      18 antibodies are in clinical trials. This review updates the biology of IL-18 as
      well as its role in human disease. 

PMID- 24115950
TI  - Antigen Mimicry between Infectious Agents and Self or Environmental Antigens May
      Lead to Long-Term Regulation of Inflammation.

PMID- 24115949
TI  - Location, location, location: the impact of migratory heterogeneity on T cell
      function.
AB  - T cell migration is crucial for an effective adaptive immune response to invading
      pathogens. Naive and memory T cells encounter pathogen antigens, become
      activated, and differentiate into effector cells in secondary lymphoid tissues,
      and then migrate to the site(s) of infection where they exert effector activities
      that control and eliminate pathogens. To achieve activation, efficient effector
      function, and good memory formation, T cells must traffic between lymphoid and
      non-lymphoid tissues within the body. This complex process is facilitated by
      chemokine receptors, selectins, CD44, and integrins that mediate the interactions
      of T cells with the environment. The expression patterns of these migration
      receptors (MR) dictate the tissues into which the effector T cells migrate and
      enable them to occupy specific niches within the tissue. While MR have been
      considered primarily to facilitate cell movement, we highlight how the
      heterogeneity of signaling through these receptors influences the function and
      fate of T cells in situ. We explore what drives MR expression heterogeneity, how
      this affects migration, and how this impacts T cell effector function and memory
      formation. 

PMID- 24115951
TI  - Overexpression of chloroplast NADPH-dependent thioredoxin reductase in
      Arabidopsis enhances leaf growth and elucidates in vivo function of reductase and
      thioredoxin domains.
AB  - Plant chloroplasts have versatile thioredoxin systems including two thioredoxin
      reductases and multiple types of thioredoxins. Plastid-localized NADPH-dependent
      thioredoxin reductase (NTRC) contains both reductase (NTRd) and thioredoxin
      (TRXd) domains in a single polypeptide and forms homodimers. To study the action
      of NTRC and NTRC domains in vivo, we have complemented the ntrc knockout line of
      Arabidopsis with the wild type and full-length NTRC genes, in which 2-Cys motifs
      either in NTRd, or in TRXd were inactivated. The ntrc line was also transformed
      either with the truncated NTRd or TRXd alone. Overexpression of wild-type NTRC
      promoted plant growth by increasing leaf size and biomass yield of the rosettes.
      Complementation of the ntrc line with the full-length NTRC gene containing an
      active reductase but an inactive TRXd, or vice versa, recovered wild-type
      chloroplast phenotype and, partly, rosette biomass production, indicating that
      the NTRC domains are capable of interacting with other chloroplast thioredoxin
      systems. Overexpression of truncated NTRd or TRXd in ntrc background did not
      restore wild-type phenotype. Modeling of the three-dimensional structure of the
      NTRC dimer indicates extensive interactions between the NTR domains and the TRX
      domains further stabilize the dimeric structure. The long linker region between
      the NTRd and TRXd, however, allows flexibility for the position of the TRXd in
      the dimer. Supplementation of the TRXd in the NTRC homodimer model by free
      chloroplast thioredoxins indicated that TRXf is the most likely partner to
      interact with NTRC. We propose that overexpression of NTRC promotes plant biomass
      yield both directly by stimulation of chloroplast biosynthetic and protective
      pathways controlled by NTRC and indirectly via free chloroplast thioredoxins. Our
      data indicate that overexpression of chloroplast thiol redox-regulator has a
      potential to increase biofuel yield in plant and algal species suitable for
      sustainable bioenergy production. 

PMID- 24115948
TI  - The structural basis of antibody-antigen recognition.
AB  - The function of antibodies (Abs) involves specific binding to antigens (Ags) and
      activation of other components of the immune system to fight pathogens. The six
      hypervariable loops within the variable domains of Abs, commonly termed
      complementarity determining regions (CDRs), are widely assumed to be responsible
      for Ag recognition, while the constant domains are believed to mediate effector
      activation. Recent studies and analyses of the growing number of available Ab
      structures, indicate that this clear functional separation between the two
      regions may be an oversimplification. Some positions within the CDRs have been
      shown to never participate in Ag binding and some off-CDRs residues often
      contribute critically to the interaction with the Ag. Moreover, there is now
      growing evidence for non-local and even allosteric effects in Ab-Ag interaction
      in which Ag binding affects the constant region and vice versa. This review
      summarizes and discusses the structural basis of Ag recognition, elaborating on
      the contribution of different structural determinants of the Ab to Ag binding and
      recognition. We discuss the CDRs, the different approaches for their
      identification and their relationship to the Ag interface. We also review what is
      currently known about the contribution of non-CDRs regions to Ag recognition,
      namely the framework regions (FRs) and the constant domains. The suggested
      mechanisms by which these regions contribute to Ag binding are discussed. On the
      Ag side of the interaction, we discuss attempts to predict B-cell epitopes and
      the suggested idea to incorporate Ab information into B-cell epitope prediction
      schemes. Beyond improving the understanding of immunity, characterization of the
      functional role of different parts of the Ab molecule may help in Ab engineering,
      design of CDR-derived peptides, and epitope prediction. 

PMID- 24115952
TI  - Partitioning, repressing and derepressing: dynamic regulations in MLA immune
      receptor triggered defense signaling.
AB  - Plants and animals have evolved intracellular nucleotide-binding domain and
      leucine-rich repeat-containing immune receptors (NLRs) to perceive non-self and
      trigger immune responses. Plant NLRs detect strain-specific pathogen effectors
      and activate immune signaling leading to extensive transcriptional reprogramming
      and termination of pathogen infection. Here we review the recent findings in
      barley MLA immune receptor mediated immune responses against the barley powdery
      mildew fungus. We focus on nucleocytoplasmic partitioning of immune receptor,
      bifurcation of immune signaling, transcriptional repression and derepression
      connecting receptor activation to immune responses. We also discuss similar
      findings from other plant NLRs where appropriate. 

PMID- 24115954
TI  - Morphometric and volumetric study of caudate and putamen nuclei in normal
      individuals by MRI: Effect of normal aging, gender and hemispheric differences.
AB  - BACKGROUND: The aim of this study was to determine age, gender, and hemispheric
      differences in the volume of the human neostriatum (striatum) nucleus in healthy
      humans. MATERIAL/METHODS: This study was performed on 120 normal human subjects
      (60 males, 60 females, right-handed) 15-65 years old, divided into two groups:
      young (<40 yrs) and old (=>=40 yrs). Sectional brain images were obtained via
      magnetic resonance imaging (MRI), analyzed and processed using the Image-J
      software, and the striatum volume was calculated using the Cavalieri's principle,
      retrospectively. RESULTS: The analyses revealed bilateral age-related shrinkage
      of the putamen in both genders and the putamen and caudate nucleus were
      significantly smaller in older than in younger subjects (P-value <0.001). The age
      related shrinkage of the caudate and putamen nucleus in men and women was about
      5%, 5% and 4%, 4%, respectively, and there were statistically significant volume
      differences between males and females (P-value <0.05). In both genders, a
      significant rightward asymmetry was observed in the caudate and putamen nucleus
      (3.89%, 4.21% in men and 4.51%, 3.32% in women). CONCLUSIONS: Bilateral age
      related shrinkage and rightward asymmetry of the striate nucleus was found in
      healthy adults and there were significant volume differences between men and
      women. Obtained results provide useful baseline data on age and gender-related
      changes of the volume of the striatum.

PMID- 24115955
TI  - Differentiation between sarcoidosis and Hodgkin's lymphoma based on mediastinal
      lymph node involvement pattern: Evaluation using spiral CT scan.
AB  - BACKGROUND: The purpose of this study was to determine the specific and detailed
      anatomic sites and morphologic characteristics of mediastinal lymph nodes on
      spiral computed tomography for the purpose of differentiation between sarcoidosis
      and Hodgkin's lymphoma. MATERIAL/METHODS: Anatomical distribution of mediastinal
      lymph nodes on spiral CT was reviewed in 39 patients with sarcoidosis and 37
      patients with Hodgkin's lymphoma using the International Association for the
      Study of Lung Cancer (IASLC) lymph node map. Other morphologic features such as
      lymph node calcification or coalescence of adjacent lymph nodes were also
      compared. RESULTS: Zone 10 was involved more often in sarcoidosis than in
      Hodgkin's lymphoma. On the other hand, there was a higher tendency for presence
      of zone 1 and 3 as well as retrocrural and internal mammary lymphadenopathy in
      Hodgkin's lymphoma than in sarcoidosis. Sarcoidosis presented with intranodal
      calcifications more often than Hodgkin's lymphoma. Coalescence, pressure effect
      on adjacent structures and central cavitations were significantly more common in
      Hodgkin's lymphoma. CONCLUSIONS: Findings of the present study indicate that
      specific anatomical distribution and morphological patterns of mediastinal lymph
      nodes, as demonstrated on spiral CT, can be useful in differentiating sarcoidosis
      from Hodgkin's lymphoma.

PMID- 24115953
TI  - Chromatin-based epigenetics of adult subventricular zone neural stem cells.
AB  - In specific regions of the adult mammalian brain, neural stem cells (NSCs)
      generate new neurons throughout life. Emerging evidence indicate that chromatin
      based transcriptional regulation is a key epigenetic mechanism for the life-long
      function of adult NSCs. In the adult mouse brain, NSCs in the subventricular zone
      (SVZ) retain the ability to produce both neurons and glia for the life of the
      animal. In this review, we discuss the origin and function of SVZ NSCs as they
      relate to key epigenetic concepts of development and potential underlying
      mechanism of chromatin-based transcriptional regulation. A central point of
      discussion is how SVZ NSCs - which possess many characteristics of mature, non
      neurogenic astrocytes - maintain a "youthful" ability to produce both neuronal
      and glial lineages. In addition to reviewing data regarding the function of
      chromatin-modifying factors in SVZ neurogenesis, we incorporate our growing
      understanding that long non-coding RNAs serve as an important element to
      chromatin-based transcriptional regulation, including that of SVZ NSCs.
      Discoveries regarding the epigenetic mechanisms of adult SVZ NSCs may provide key
      insights into fundamental principles of adult stem cell biology as well as the
      more complex and dynamic developmental environment of the embryonic brain. 

PMID- 24115956
TI  - Evaluation of usefulness of scintigraphic imaging in diagnosis of intrathecal
      drug delivery system malfunction - a preliminary report.
AB  - BACKGROUND: Implantable intrathecal drug delivery systems (IDDS) are basic tool
      enabling chronic intrathecal pharmacotherapy. Lack of expected clinical results
      of IDDS therapy necessitates search for the cause with the help of diagnostic
      imaging methods among other things. Beside radiological techniques, it is also
      possible to visually assess IDDS systems by nuclear medicine methods. In this
      study we assess utility of radioisotopic methods in differential diagnosis of
      failure of therapy with IDDS systems. MATERIAL/METHODS: Scintigraphic studies
      were performed in selected patients with neurological diseases associated with
      spasticity, who had IDDS system implanted and were unable to maintain satisfying
      clinical effect of inrathecally infused baclofen. After emptying the IDDS system
      of the drug, radiotracer (99mTc-DTPA) solution was injected into the pump
      reservoir. Subsequently, a series of scintigraphic images was registered,
      demonstrating passage and distribution of the infused radiotracer. RESULTS: In
      all investigated cases, scintigraphic study resulted in acquiring relevant
      additional diagnostic information. Normal or disrupted distribution of
      radiotracer in spinal canal allowed for a diagnosis drug resistance or
      demonstrated presence of arachnoid adhesions respectively. Early appearance of
      radiotracer in blood was considered a proof of leak. Our examinations had
      decisive influence on further patient treatment, allowing for diagnosis of drug
      resistance in one patient or complication related to IDDS system in three other
      cases including breakage of a catheter, pump malfunction and arachnoid adhesions.
      CONCLUSIONS: Scintigraphic methods carry significant amount of information
      facilitating final diagnosis of the cause of IDDS therapy failure. They should
      become an important element complementing the diagnostic strategy in patients
      with suspected failure of intrathecal drug administration systems. Interpretation
      of radioisotopic studies, since they are purely functional, must be performed in
      strict relation to clinical data and radiological examinations as they carry
      indispensable, basic information regarding morphology.

PMID- 24115957
TI  - MDCTA diagnosis of cerebral vessel disease among patients with arterial
      hypertension.
AB  - BACKGROUND: to study changes involving cerebral vessels in patients with
      hypertension and various levels of total cardiovascular risk. MATERIAL/METHODS:
      One hundred and thirty-four patients underwent CT-angiography of intracranial
      vessels. Ninety-eight of them were diagnosed with hypertension. Taking into
      consideration high blood pressure, presence of risk factors and target organ
      damage subjects were divided into 4 groups: with low, medium, high and very high
      total cardiovascular risk. Control group included 36 patients. They were not
      diagnosed with hypertension at the time of examination. One hundred and five
      patients were examined using a 4-slice CT scanner (Toshiba Asteion 4, Toshiba
      Medical System, Japan), and 29 patients were examined using a 128-slice scanner
      (Siemens Definition AS+, Siemens Healthcare, Germany) with an injection system.
      We used iodine-containing contrast agents such as iodixanol and iopromide for
      angiography. RESULTS: Anatomical and topographic changes of cerebral vessels were
      most frequently found in hypertensive patients with high and very high total
      cardiovascular risk. Narrowing of vertebral vessels was the most common change
      (27 patients (27.55%), 21 patients (21.43%) had narrowing of the right artery,
      and 6 (6.12%) subjects - of the left one). Tortuous course of internal carotid
      arteries at the neck level was visualized in 11 patients (11.22%). Narrowing of
      A1 segment of anterior cerebral artery was noted in 9 patients (9.18%), of the
      right one - in 8 patients (8.16%), of the left one - in 1 patient (1.02%).
      Aneurysmal dilation of intracranial vessels was visualized in 6 patients (6.12%).
      Saccular aneurysm of left internal carotid artery was diagnosed in 2 patients
      (2.04%), one patient (1.02%) had right internal carotid artery aneurysm and one
      patient (1.02%) had an aneurysm of the basilar artery. DISCUSSIONS: the most
      common changes of cerebral vessels diagnosed in MDCTA among patients with
      hypertension included various degrees of narrowing of vertebral vessels,
      anterior, posterior and posterior communicating arteries and internal carotid
      arteries. Changes of middle cerebral arteries and basilar arteries were extremely
      rare, thus we can say that these vessels are influenced by high blood pressure to
      lesser extent. We established the relationship between changes in cerebral blood
      vessels and total cardiovascular risk. Therefore, we believe that findings will
      be useful for establishing prognosis in hypertension and prevention of
      complications such as stroke. CONCLUSIONS: MDCT angiography is a highly
      informative method to study changes of cerebral vessels in patients with
      hypertension. The relationship between changes in cerebral blood vessels
      diagnosed through MDCT angiography and the level of total cardiovascular risk
      among patients with hypertension had been established.

PMID- 24115958
TI  - Onyx((r)) in endovascular treatment of cerebral arteriovenous malformations - a
      review.
AB  - Arteriovenous malformation (AVM) is an abnormal connection between arteries and
      veins, bypassing the capillary system. In most cases, the disorder may be
      asymptomatic. The objective of endovascular AVM treatment is set individually for
      each case upon consultations with a neurosurgeon and a neurologist. The endpoint
      of the treatment should consist in prevention of AVM bleeding in a management
      procedure characterized by a significantly lower risk of complications as
      compared to the natural history of AVM. Endovascular interventions within AVM may
      include curative exclusion of AVM from circulation, embolization adjuvant to
      resection or radiation therapy, targeted closure of a previously identified
      bleeding site as well as palliative embolization. Onyx was first described in the
      1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the
      lumen of the targeted vessel is obtained by means of precipitation. The process
      is enhanced peripherally to the main flux of the injected mixture. This
      facilitates angiographic monitoring of embolization at any stage. The degree of
      lumen closure is associated with the location of the vessel. Supratentorial and
      cortical locations are most advantageous. Dense and plexiform structure of AVM
      nidus as well as a low number of supplying vessels and a single superficial
      drainage vein are usually advantageous for Onyx administration. Unfavorable
      factors include nidus drainage into multiple compartments as well as
      multiarterial supply of the AVM, particularly from meningeal arteries, en-passant
      arteries or perforating feeders. Onyx appears to be a safe and efficient material
      for embolization of cerebral AVMs, also in cases of intracranial bleeding
      associated with AVM. Curative embolization of small cerebral AVMs is an efficient
      and safe alternative to neurosurgical and radiosurgical methods. Careful
      angiographic assessment of individual arteriovenous malformations should be
      performed before each Onyx administration. 

PMID- 24115959
TI  - Variants of cerebral arteries - anterior circulation.
AB  - Advances in imaging techniques allow for in vivo identification of abnormalities
      and normal variants of cerebral arteries. These arterial variations can be
      asymptomatic and uncomplicated although, some of them increase the risk of
      aneurysm formation, acute intracranial hemorrhage, play a vital role in
      neurosurgical planning or can be misidentified as serious pathology and medical
      errors. The goal of this publication is to discuss arterial anomalies of anterior
      cerebral circulation, their prevalence and demonstrate radiological images of
      some of those variants. In this article we will discuss variants of internal
      carotid artery, anterior cerebral artery, anterior communicating artery, middle
      cerebral artery, persistent stapedial artery and fenestration. 

PMID- 24115960
TI  - Current imaging techniques in rheumatology: MRI, scintigraphy and PET.
AB  - The first-line imaging technique for diagnosis inflammation in musculo-skeletal
      organs in rheumatoid arthritis (RA) is planar X-ray examination, which was for
      many years the first and the only single tool for RA diagnostics and response
      evaluation. Today, in the era of more aggressive RA treatment, ultrasound
      examination (US) and magnetic resonance imaging (MRI) are also frequently used.
      US is used to detect early signs of inflammation within the soft tissue. MRI
      allows to assess the soft tissue and bone marrow involvement in case of
      inflammation and/or infection. MRI is capable of detecting more inflammatory
      lesions and erosions than US, X-ray, or CT. Standard scintigraphy plays a crucial
      role, and data from positron emission tomography (PET) are also promising. These
      functional imaging techniques are used in detection of inflammation and/or
      infection in case of ambiguous results being obtained by other techniques or at
      other clinics. In patients with RA, scintigraphy plays a key role in the
      differential diagnosis of hip, knee, etc. endoprosthesis disorders, including
      mechanical or septic loosening. 

PMID- 24115961
TI  - Miliary brain metastases from papillary adenocarcinoma of the lung - unusual MRI
      pattern with histopathologic correlation.
AB  - Miliary brain metastases are very rarely described in the literature but if they
      are, they are quite obvious on magnetic resonance imaging (MRI) and enhance after
      intravenous administration of the contrast medium. The authors presented a case
      of miliary metastatic spread to the brain which was invisible on computed
      tomography and hardly visible on MRI, i.e. as countless, tiny, slightly T1
      hyperintense foci that did not enhance. The authors discussed a few T1
      hyperintense brain lesions which did not include metastases (except for
      metastatic melanoma which was a radiological suggestion after brain MRI). Autopsy
      revealed papillary adenocarcinoma of the lung with numerous metastatic lesions in
      both cerebral and cerebellar hemispheres and the meninges. 

PMID- 24115962
TI  - CT and MRI imaging of the brain in MELAS syndrome.
AB  - BACKGROUND: MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic
      acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to
      a group of mitochondrial metabolic diseases. As other diseases in this group, it
      is inherited in the maternal line. CASE REPORT: In this report, we discussed a
      case of a 10-year-old girl with clinical and radiological picture of MELAS
      syndrome. We would like to describe characteristic radiological features of MELAS
      syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis.
      CONCLUSIONS: The rarity of this disorder and the complexity of its clinical
      presentation make MELAS patients among the most difficult to diagnose. Brain
      imaging studies require a wide differential diagnosis, primarily to distinguish
      between MELAS and ischemic stroke. Particularly helpful are the MRI and MR
      spectroscopy techniques.

PMID- 24115963
TI  - Perfusion and spectroscopy magnetic resonance imaging in a case of lymphocytic
      vasculitis mimicking brain tumor.
AB  - BACKGROUND: Lymphocytic vasculitis of the central nervous system is an uncommon
      subtype of primary angiitis of the central nervous system (PACNS) - a rare
      inflammatory disorder affecting parenchymal and leptomeningeal arteries and
      veins. CASE REPORT: Establishing diagnosis on the basis of neuroimaging only is
      difficult, as it can mimic a brain tumor. Thus, histological diagnosis is
      essential for appropriate management. We present a case of biopsy-proven
      lymphocytic vasculitis mimicking a brain tumor on neuroimaging that was
      subsequently successfully treated with steroid therapy. We also discuss the
      findings in perfusion MR (PWI) and MR spectroscopy (MRS). CONCLUSIONS: Regional
      hypoperfusion on PWI and elevation of glutamate and glutamine levels on MRS
      (without associated typical tumor spectra) are common findings in inflammatory
      disorders, including PACNS, and can be useful in differential diagnosis with
      tumors.

PMID- 24115964
TI  - A huge duplication cyst of the ileum.
AB  - BACKGROUND: Massive unilocular intraabdominal cysts in children are rare.
      Alimentary tract duplications can present diagnostic and therapeutic
      difficulties. Although they can occur anywhere from the mouth to the anus, they
      are commonly seen in relation to the ileum. We herein present an unusual case of
      duplication cyst itself occupying virtually all of the available intraabdominal
      volume. It appeared to be an enteric duplication cyst of ileal origin. CASE
      REPORT: A 3-month-old girl was admitted to our hospital for investigation of
      progressive abdominal distension and biliary vomiting. Plain radiography of the
      abdomen showed normal air-fluid level in the stomach and paucity of gases in rest
      of the abdomen. Magnetic resonance imaging showed a huge, homogenous cyst
      extending from the xiphisternum down to the pelvis. The cyst was excised
      completely. Macroscopic examination and histologic findings confirmed the
      diagnosis of a huge enteric duplication cyst arising from the ileum. CONCLUSIONS:
      Enteric duplication cyst should be considered in a patient with an abdominal
      cystic mass. Radiologist must take into account patient age, clinical parameters,
      and imaging findings to identify the likely etiology of a cystic mass.

PMID- 24115965
TI  - Mechanical thrombectomy using Rotarex system and stent-in-stent placement for
      treatment of distal femoral artery occlusion secondary to stent fracture - a case
      report and literature review.
AB  - BACKGROUND: Treatment of peripheral arterial diseases may be distinguished into
      conservative and interventional management; the latter is divided into surgical
      and endovascular procedures. Management of peripheral artery stenosis and
      occlusion with vascular stents is associated with the risk of late complications
      such as restenosis, stent fracture or dislocation. CASE REPORT: A 62-year-old
      woman with generalized atherosclerosis, particularly extensive in lower limb
      arteries, was admitted to the Department of Angiology 11 months after having an
      endovascular procedure performed due to critical ischemia of left lower limb.
      Because of stent occlusion, a decision to perform angiographic examination of
      lower limb arteries was made. Examination revealed occlusion of the superficial
      femoral artery along its entire length, including previously implanted stents.
      Distal stent was fractured with slight dislocation of the proximal segment. A
      decision was made to perform mechanical thrombectomy using a Rotarex system
      followed by a stent-in-stent placement procedure. Follow-up angiography and
      ultrasound scan performed 24 hours after the procedure revealed a patent vessel
      with satisfactory blood flow. DISCUSSION: Nowadays, imaging diagnostics of
      peripheral artery stenosis involves non-invasive examinations such as ultrasound,
      minimally invasive examinations such as angio-MRI and MDCT, or invasive
      examinations such as DSA and IVUS. DSA examinations are used to confirm
      significant stenosis or occlusion of a vessel, particularly when qualifying a
      patient for endovascular treatment. Due to their anatomic location, the
      superficial femoral artery and the popliteal artery are subject to various forces
      e.g. those exerted by the working muscles. Mechanical thrombectomy and
      atherectomy are efficient methods of arterial recanalization used in the
      treatment of acute, subacute or even chronic occlusions or stenosis of peripheral
      vessels. CONCLUSIONS: Frequency of angioplasty and vascular stent implantation
      procedures is increased in patients with peripheral arterial disease, thus
      increasing the incidence of reported early and late complications such as acute
      stent thrombosis, restenosis and stent fractures. The Rotarex transcutaneous
      mechanical thrombectomy system is an efficient method of treating occlusions in
      arterial stents. It is also safe when performed by experienced operators.

PMID- 24115966
TI  - Institutional Review Boards: From Bane to Benefit.
AB  - Institutional review boards (IRBs) are primarily prevention-focused, avoiding
      damage to human subjects and averting ethical infractions, thereby protecting
      participants, researchers, and universities. Yet, the cost of prevention focus is
      simply avoiding negative outcomes and is enacted through control, risk-aversion,
      security, detail-orientation, reactivity, anxiety, avoidance, punishment,
      negative possibilities, and seizing on a single dominant solution. These endanger
      the research enterprise. An alternative promotion focus is more advantageous as
      it seeks positive outcomes and thus facilitating research, which is the IRB s
      second duty. This alternative guides recruiting and training of staff, panel, and
      researchers; orienting to and reinforcing promotion norms; creating well-known,
      transparent, responsive, and efficient processes; and understanding the IRB's
      boundaries. Promotion balances prevention to make IRBs support research and
      protect subjects. 

PMID- 24115967
TI  - No Correlations Between the Development of Specific IgA and IgM Antibodies
      Against Anti-TNF Blocking Agents, Disease Activity and Adverse Side Reactions in
      Patients with Rheumatoid Arthritis.
AB  - The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept
      [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases,
      including rheumatoid arthritis (RA). However, some questions concerning their
      safety have emerged since their approval because they can trigger immunisation,
      induce rare type I and III hypersensitivity, and cause acute and delayed
      reactions. The aim of this study was to evaluate the correlations between
      hypersensitivity reactions to biological agents, disease activity and the
      development of class-specific IgA and IgM antibodies against the three anti-TNF
      agents in patients with RA. This longitudinal observational study involved
      consecutive outpatients with active RA who started treatment with IFN (n=30), ETN
      (n=41) or ADA (n=28). Clinical data and systemic and local side effects were
      collected prospectively at baseline and after six months of anti-TNF treatment.
      Serum samples were taken at the same time points in order to measure antibodies
      against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA
      and IgM antibodies specific to all three anti-TNF-alpha agents were analysed
      using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with
      the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean
      age of the 99 patients (86% females) was 54.6+/-12.4 years, and the median
      disease duration was 11.2+/-.3.2 years (range 3-14.3). The three treatment groups
      were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated
      peptide (CCP) antibody positivity, and baseline C-reactive protein levels,
      erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant
      medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two
      (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four
      (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and
      24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and
      seven adverse local reactions in both the ADA and the ETN group. There was no
      correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also
      no correlation between the antibodies and disease activity after six months of
      treatment (r=0.189;p=0.32). Our findings show that the development of antibodies
      against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in
      efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to
      systemic and local reactions. Further studies of larger series of RA patients are
      needed to confirm the relationships between the development of drug-specific
      antibodies, serum TNF blocker levels, and disease activity. 

PMID- 24115968
TI  - Results of an International Survey of Practice Patterns for Establishing
      Prognosis in Neck Pain: The ICON Project.
AB  - Results of an international survey of health care providers for neck pain are
      reported. The survey specifically collected self-reported practice patterns for
      establishing a prognosis in neck pain. Over 440 responses from 27 countries were
      collected. Descriptive results indicate that respondents assigned large
      prognostic impact to factors including mechanism of injury and psychological or
      behavioral constructs. Range of motion, age and sex were routinely collected
      despite relatively moderate impact on prognosis. A comparison between
      chiropractic and manual/physical therapy groups showed differences in practice
      patterns that were unlikely to affect prognostic accuracy. The results suggest a
      gap exists between current best-evidence and actual practice when the goal is to
      establish a prognosis in neck pain. 

PMID- 24115969
TI  - What does 'recovery' mean to people with neck pain? Results of a descriptive
      thematic analysis.
AB  - OBJECTIVES: To describe the meaning of being recovered as perceived by people
      with chronic mechanical neck pain. METHODS: To determine the way people with neck
      pain would describe a recovered state a descriptive thematic approach was used. A
      nominal focus group technique, written reflections, and one-on-one semi
      structured interviews were used to collect sufficient data. Data from the focus
      groups were analyzed both through vote tallying and thematic analysis.
      Reflections and interviews were analyzed thematically by two independent
      researchers. Triangulation and member-checking were employed to establish
      trustworthiness of results. RESULTS: A total of 35 people, primarily females with
      neck pain of traumatic origin, participated in this study. Thematic analysis
      identified 6 themes that adequately described the data: absent or manageable
      symptoms, having the physical capacity one ought to have, participation in life
      roles, feeling positive emotions, autonomy & spontaneity, and re-establishing a
      sense of self. Member checking and triangulation suggested data saturation and
      accuracy of the generated themes. DISCUSSION: Recovery from neck pain appears to
      be informed by factors that fit with existing models of health, quality of life
      and satisfaction. Basing recovery solely on symptom or activity-level measures
      risks inaccurate estimates of recovery trajectories from traumatic or non
      traumatic neck pain.

PMID- 24115970
TI  - A description of the methodology used in an overview of reviews to evaluate
      evidence on the treatment, harms, diagnosis/classification, prognosis and
      outcomes used in the management of neck pain.
AB  - BACKGROUND: Neck Pain (NP) is a common musculoskeletal disorder and the
      literature provides conflicting evidence about its management. OBJECTIVE: To
      describe the methodology used to conduct an overview of reviews (OvR) and to
      characterize the distribution and risk of bias profiles across the evidence for
      all areas of NP management. METHODS: Standard systematic review (SR) methodology
      was employed. MEDLINE, CINAHL, EMBASE, ILC, Cochrane CENTRAL, and LILACS were
      searched from 2000 to March 2012; Narrative and SR and clinical practice
      guidelines (CPG) evaluating the efficacy of treatment (benefits and harms),
      diagnosis/classification, prognosis, and outcomes were eligible. For treatment,
      articles were limited to SRs from 2005 forward. Risk of bias of SR was assessed
      with the AMSTAR; the AGREE II was used to critically appraise the CPGs. RESULTS:
      From 2476 articles, 508 were eligible for full text screening. A total of 341
      articles were included. Treatment (n=117) had the greatest yield. Other clinical
      areas had less literature (diagnosis=54, prognosis=16, outcomes=27, harms=16).
      There were no SR for classification and narrative reviews were problematic for
      this topic. There was great overlap across different databases within each
      clinical area except for those for outcome measures. Risk of bias assessment
      using the AMSTAR of eligible SRs showed a similar trend across different clinical
      areas. CONCLUSION: A summary of methods used to review the literature in five
      clinical areas of NP management have been described. The challenges of selecting
      and synthesizing eligible articles in an OvR required customized solutions across
      different areas of clinical focus.

PMID- 24115971
TI  - An Overview of Systematic Reviews on Prognostic Factors in Neck Pain: Results
      from the International Collaboration on Neck Pain (ICON) Project.
AB  - Given the challenges of chronic musculoskeletal pain and disability, establishing
      a clear prognosis in the acute stage has become increasingly recognized as a
      valuable approach to mitigate chronic problems. Neck pain represents a condition
      that is common, potentially disabling, and has a high rate of transition to
      chronic or persistent problems. As a field of research, prognosis in neck pain
      has stimulated several empirical primary research papers, and a number of
      systematic reviews. As part of the International Consensus on Neck (ICON)
      project, we sought to establish the general state of knowledge in the area
      through a structured, systematic review of systematic reviews (overview). An
      exhaustive search strategy was created and employed to identify the 13 systematic
      reviews (SRs) that served as the primary data sources for this overview. A
      decision algorithm for data synthesis, which incorporated currency of the SR,
      risk of bias assessment of the SRs using AMSTAR scoring and consistency of
      findings across SRs, determined the level of confidence in the risk profile of
      133 different variables. The results provide high confidence that baseline neck
      pain intensity and baseline disability have a strong association with outcome,
      while angular deformities of the neck and parameters of the initiating trauma
      have no effect on outcome. A vast number of predictors provide low or very low
      confidence or inconclusive results, suggesting there is still much work to be
      done in this field. Despite the presence of multiple SR and this overview, there
      is insufficient evidence to make firm conclusions on many potential prognostic
      variables. This study demonstrates the challenges in conducting overviews on
      prognosis where clear synthesis critieria and a lack of specifics of primary data
      in SR are barriers. 

PMID- 24115972
TI  - Use of outcome measures in managing neck pain: an international multidisciplinary
      survey.
AB  - PURPOSE: To determine the outcome measures practice patterns in the neck pain
      management of various health disciplines. METHODS: A survey of 381 clinicians
      treating patients with neck pain was conducted. RESULTS: Respondents were more
      commonly male (54%) and either chiropractors (44%) or physiotherapists (32%). The
      survey was international (24 countries with Canada having the largest response
      (44%)). The most common assessment was a single-item pain assessment (numeric or
      visual analog) used by 75% of respondents. Respondents sometimes or routinely
      used the Neck Disability Index (49%), the Patient Specific Functional Scale
      (28%), and the Disabilities of the Arm, Shoulder and Hand (32%). Work status was
      recorded in terms of time lost by more than 50% of respondents, but standardized
      measures of work limitations or functional capacity testing were rarely used. The
      majority of respondents never used fear of movement, psychological distress,
      quality of life, participation measures, or global ratings of change (< 10%
      routinely use). Use of impairment measurers was prevalent, but the type selected
      was variable. Quantitative sensory testing was used sometimes or routinely by 53%
      of respondents, whereas 26% never used it. Ratings of segmental joint mobility
      were commonly used to assess motion (44% routinely use), whereas 66% of
      respondents never used inclinometry. Neck muscle strength, postural alignment and
      upper extremity coordination were assessed sometimes or routinely by a majority
      of respondents (>56%). With the exception of numeric pain ratings and verbal
      reporting of work status, all outcomes measures were less frequently used by
      physicians. Years of practice did not affect practice patterns, but reimbursement
      did affect selection of some outcome measures. CONCLUSIONS: Few outcome measures
      are routinely used to assess patients with neck pain other than a numeric pain
      rating scale. A comparison of practice patterns to current evidence suggessts
      overutilization of some measures that have questionable reliability and
      underutilization of some with better supporting evidence. This practice analysis
      suggests that there is substantial need to implement more consistent outcome
      measurement in practice. International consensus and better clinical measurement
      evidence are needed to support this.

PMID- 24115973
TI  - Applications of a New Handheld Reference Point Indentation Instrument Measuring
      Bone Material Strength.
AB  - A novel, hand-held Reference Point Indentation (RPI) instrument, measures how
      well the bone of living patients and large animals resists indentation. The
      results presented here are reported in terms of Bone Material Strength, which is
      a normalized measure of how well the bone resists indentation, and is inversely
      related to the indentation distance into the bone. We present examples of the
      instrument's use in: (1) laboratory experiments on bone, including experiments
      through a layer of soft tissue, (2) three human clinical trials, two ongoing in
      Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two
      ongoing horse clinical trials, one at Purdue University and another at Alamo
      Pintado Stables in California. The instrument is capable of measuring consistent
      values when testing through soft tissue such as skin and periosteum, and does so
      handheld, an improvement over previous Reference Point Indentation instruments.
      Measurements conducted on horses showed reproducible results when testing the
      horse through tissue or on bare bone. In the human clinical trials, reasonable
      and consistent values were obtained, suggesting the Osteoprobe(r) is capable of
      measuring Bone Material Strength in vivo, but larger studies are needed to
      determine the efficacy of the instrument's use in medical diagnosis.

PMID- 24115974
TI  - Development of a Portable Knee Rehabilitation Device That Uses Mechanical
      Loading.
AB  - Joint loading is a recently developed mechanical modality, which potentially
      provides a therapeutic regimen to activate bone formation and prevent degradation
      of joint tissues. To our knowledge, however, few joint loading devices are
      available for clinical or point-of-care applications. Using a voice-coil
      actuator, we developed an electromechanical loading system appropriate for human
      studies and preclinical trials that should prove both safe and effective. Two
      specific tasks for this loading system were development of loading conditions
      (magnitude and frequency) suitable for humans, and provision of a convenient and
      portable joint loading apparatus. Desktop devices have been previously designed
      to evaluate the effects of various loading conditions using small and large
      animals. However, a portable knee loading device is more desirable from a
      usability point of view. In this paper, we present such a device that is designed
      to be portable, providing a compact, user-friendly loader. The portable device
      was employed to evaluate its capabilities using a human knee model. The portable
      device was characterized for force-pulse width modulation duty cycle and loading
      frequency properties. The results demonstrate that the device is capable of
      producing the necessary magnitude of forces at appropriate frequencies to promote
      the stimulation of bone growth and which can be used in clinical studies for
      further evaluations.

PMID- 24115996
TI  - Remote measurements of heart and respiration rates for telemedicine.
AB  - Non-contact and low-cost measurements of heart and respiration rates are highly
      desirable for telemedicine. Here, we describe a novel technique to extract blood
      volume pulse and respiratory wave from a single channel images captured by a
      video camera for both day and night conditions. The principle of our technique is
      to uncover the temporal dynamics of heart beat and breathing rate through delay
      coordinate transformation and independent component analysis-based deconstruction
      of the single channel images. Our method further achieves robust elimination of
      false positives via applying ratio-variation probability distributions filtering
      approaches. Moreover, it enables a much needed low-cost means for preventing
      sudden infant death syndrome in new born infants and detecting stroke and heart
      attack in elderly population in home environments. This noncontact-based method
      can also be applied to a variety of animal model organisms for biomedical
      research. 

PMID- 24115997
TI  - Factors influencing early and late mortality in adults with invasive pneumococcal
      disease in Calgary, Canada: a prospective surveillance study.
AB  - BACKGROUND: Invasive pneumococcal disease continues to be an important cause of
      mortality. In Calgary, 60% of deaths occur within 5 days of presenting to
      hospital. This proportion has not changed since before the era of penicillin. The
      purpose of this study was to investigate what factors may influence death within
      5 days of presentation with pneumococcal disease. METHODS AND FINDINGS:
      Demographic and clinical data from the CASPER (Calgary Area Streptococcus
      pneumoniae Epidemiology Research) study on 1065 episodes of invasive pneumococcal
      disease in adults (>=18 years) from 2000 to 2010 were analyzed. Adjusted
      multinomial regression was performed to analyze 3 outcomes: early mortality (<5
      days post-presentation), late mortality (5-30 days post-presentation), and
      survival, generating relative risk ratios (RRR). Patients with severe disease had
      increased risk of early and late death. In multinomial regression with survivors
      as baseline, the risk of early death increased in those with a Charlson index >=2
      (RRR: 6.3, 95% CI: 1.8-21.9); the risk of late death increased in those with less
      severe disease and a Charlson >=2 (RRR: 6.1, 95% CI: 1.4-27.7). Patients who
      never received appropriate antibiotics had 5.6X (95% CI: 2.4-13.1) the risk of
      early death. Risk of both early and late death increased by a RRR of 1.3 (95% CI:
      1.2-1.4) per 5-year increase in age. In multinomial regression, there were no
      significant differences in the effects of the factors tested between early and
      late mortality. CONCLUSIONS: Presenting with severe invasive pneumococcal
      disease, multiple comorbidities, and older age increases the risk of both early
      and late death. Patients who died early often presented too late for effective
      antibiotic therapy, highlighting the need for an effective vaccine.

PMID- 24115998
TI  - Accurate LC peak boundary detection for 16O/18O labeled LC-MS data.
AB  - In liquid chromatography-mass spectrometry (LC-MS), parts of LC peaks are often
      corrupted by their co-eluting peptides, which results in increased quantification
      variance. In this paper, we propose to apply accurate LC peak boundary detection
      to remove the corrupted part of LC peaks. Accurate LC peak boundary detection is
      achieved by checking the consistency of intensity patterns within peptide elution
      time ranges. In addition, we remove peptides with erroneous mass assignment
      through model fitness check, which compares observed intensity patterns to
      theoretically constructed ones. The proposed algorithm can significantly improve
      the accuracy and precision of peptide ratio measurements. 

PMID- 24115999
TI  - Piezochromic phenomena of nanometer voids formed by mono-dispersed nanometer
      powders compacting process.
AB  - Piezochromism describes a tendency of certain materials changing colors when they
      are subjected to various pressure levels. It occurs particularly in some polymers
      or inorganic materials, such as in palladium complexes. However, piezochromism is
      generally believed to work at high pressure range of 0.1-10 GPa. This research
      work focused on unique piezochromism responses of the nanometer voids formed by
      the 5-20 nm inorganic ISOH nanometer powders. It was discovered that
      microstructures of the nanometer voids could change color at very low pressures
      of only 0.002-0.01 GPa; its sensitivity to pressure was increased by tens of
      times. It is believed that the uniform microstructures of nanometer powders
      contributed to the material's high sensitivity of piezochromic phenomena. One
      factor which quantum optical change caused by nanometer voids affected the
      quantum confinement effect; another is surface Plasmon Resonance of great
      difference dielectric property between conductive ITO powder and insulation
      hydroxide. 

PMID- 24116000
TI  - Effectiveness of cultural adaptations of interventions aimed at smoking
      cessation, diet, and/or physical activity in ethnic minorities. a systematic
      review.
AB  - BACKGROUND: The importance of cultural adaptations in behavioral interventions
      targeting ethnic minorities in high-income societies is widely recognized. Little
      is known, however, about the effectiveness of specific cultural adaptations in
      such interventions. AIM: To systematically review the effectiveness of specific
      cultural adaptations in interventions that target smoking cessation, diet, and/or
      physical activity and to explore features of such adaptations that may account
      for their effectiveness. METHODS: Systematic review using MEDLINE, PsycINFO,
      Embase, and the Cochrane Central Register of Controlled Trials registers (1997
      2009). INCLUSION CRITERIA: a) effectiveness study of a lifestyle intervention
      targeted to ethnic minority populations living in a high income society; b)
      interventions included cultural adaptations and a control group that was exposed
      to the intervention without the cultural adaptation under study; c) primary
      outcome measures included smoking cessation, diet, or physical activity. RESULTS:
      Out of 44904 hits, we identified 17 studies, all conducted in the United States.
      In five studies, specific cultural adaptations had a statistically significant
      effect on primary outcomes. The remaining studies showed no significant effects
      on primary outcomes, but some presented trends favorable for cultural
      adaptations. We observed that interventions incorporating a package of cultural
      adaptations, cultural adaptations that implied higher intensity and those
      incorporating family values were more likely to report statistically significant
      effects. Adaptations in smoking cessation interventions seem to be more effective
      than adaptations in interventions aimed at diet and physical activity.
      CONCLUSION: This review indicates that culturally targeted behavioral
      interventions may be more effective if cultural adaptations are implemented as a
      package of adaptations, the adaptation includes family level, and where the
      adaptation results in a higher intensity of the intervention. More systematic
      experiments are needed in which the aim is to gain insight in the best mix of
      cultural adaptations among diverse populations in various settings, particularly
      outside the US.

PMID- 24116001
TI  - Differential growth responses to water balance of coexisting deciduous tree
      species are linked to wood density in a Bolivian tropical dry forest.
AB  - A seasonal period of water deficit characterizes tropical dry forests (TDFs).
      There, sympatric tree species exhibit a diversity of growth rates, functional
      traits, and responses to drought, suggesting that each species may possess
      different strategies to grow under different conditions of water availability.
      The evaluation of the long-term growth responses to changes in the soil water
      balance should provide an understanding of how and when coexisting tree species
      respond to water deficit in TDFs. Furthermore, such differential growth responses
      may be linked to functional traits related to water storage and conductance. We
      used dendrochronology and climate data to retrospectively assess how the radial
      growth of seven coexisting deciduous tree species responded to the seasonal soil
      water balance in a Bolivian TDF. Linear mixed-effects models were used to
      quantify the relationships between basal area increment and seasonal water
      balance. We related these relationships with wood density and sapwood production
      to assess if they affect the growth responses to climate. The growth of all
      species responded positively to water balance during the wet season, but such
      responses differed among species as a function of their wood density. For
      instance, species with a strong growth response to water availability averaged a
      low wood density which may facilitate the storage of water in the stem. By
      contrast, species with very dense wood were those whose growth was less sensitive
      to water availability. Coexisting tree species thus show differential growth
      responses to changes in soil water balance during the wet season. Our findings
      also provide a link between wood density, a trait related to the ability of trees
      to store water in the stem, and wood formation in response to water availability.

PMID- 24116002
TI  - Comparison of allogeneic stem cell transplantation and non-transplant approaches
      in elderly patients with advanced myelodysplastic syndrome: optimal statistical
      approaches and a critical appraisal of clinical results using non-randomized
      data.
AB  - Allogeneic stem cell transplantation (ASCT) from related or unrelated donors may
      cure patients with myelodysplastic syndromes (MDS), a heterogeneous group of
      clonal stem cell disorders. We analysed 384 elderly patients (55-69 years) with
      advanced MDS who received either ASCT (n=247) and were reported to The European
      Group for Blood and Marrow Transplantation (EBMT) or a non -transplant approach
      (n=137) reported to the Dusseldorf registry. Besides an attempt to answer the
      question of "comparison", the purpose of this work is to explain the difficulties
      in comparing a non-transplant with a transplant cohort, when death before
      transplant is likely but unknown and the selection of patients for transplant is
      based on assumptions. It shows which methods are almost always biased and that
      even the most sophisticated approaches crucially rely on clinical assumptions.
      Using the most appropriate model for our data, we derive an overall univariate
      non-significant survival disadvantage for the transplant cohort (HR: 1.29, p =
      0.11). We show that such an "average" hazard ratio is however misleading due to
      non-proportionality of the hazards reflecting early treatment related mortality,
      the occurring of which is logically correlated with the interval between
      diagnosis and transplant creating a disproportional drop in the (reconstructed)
      survival curve of the transplanted patients. Also in multivariate analysis
      (correcting for age > 60 (HR: 1.4, p = 0.02) and abnormal cytogenetics (HR: 1.46,
      p = 0.01)), transplantation seems to be worse (HR: 1.39, p = 0.05) but only in
      the (incorrect but commonly applied) model without time varying covariates. The
      long term (time depending) hazard ratio is shown to be virtually 1 and overall
      survival is virtually identical in both groups. Nonetheless no conclusion can be
      reached from a clinical point of view without assumptions which are by their very
      nature untestable unless all patients would be followed from diagnosis. 

PMID- 24116003
TI  - Bayesian inference from count data using discrete uniform priors.
AB  - We consider a set of sample counts obtained by sampling arbitrary fractions of a
      finite volume containing an homogeneously dispersed population of identical
      objects. We report a Bayesian derivation of the posterior probability
      distribution of the population size using a binomial likelihood and non
      conjugate, discrete uniform priors under sampling with or without replacement.
      Our derivation yields a computationally feasible formula that can prove useful in
      a variety of statistical problems involving absolute quantification under
      uncertainty. We implemented our algorithm in the R package dupiR and compared it
      with a previously proposed Bayesian method based on a Gamma prior. As a showcase,
      we demonstrate that our inference framework can be used to estimate bacterial
      survival curves from measurements characterized by extremely low or zero counts
      and rather high sampling fractions. All in all, we provide a versatile, general
      purpose algorithm to infer population sizes from count data, which can find
      application in a broad spectrum of biological and physical problems. 

PMID- 24116004
TI  - Effects of crude oil exposure on bioaccumulation of polycyclic aromatic
      hydrocarbons and survival of adult and larval stages of gelatinous zooplankton.
AB  - Gelatinous zooplankton play an important role in marine food webs both as major
      consumers of metazooplankton and as prey of apex predators (e.g., tuna, sunfish,
      sea turtles). However, little is known about the effects of crude oil spills on
      these important components of planktonic communities. We determined the effects
      of Louisiana light sweet crude oil exposure on survival and bioaccumulation of
      polycyclic aromatic hydrocarbons (PAHs) in adult stages of the scyphozoans
      Pelagia noctiluca and Aurelia aurita and the ctenophore Mnemiopsis leidyi, and on
      survival of ephyra larvae of A. aurita and cydippid larvae of M. leidyi, in the
      laboratory. Adult P. noctiluca showed 100% mortality at oil concentration >=20 uL
      L(-1) after 16 h. In contrast, low or non-lethal effects were observed on adult
      stages of A. aurita and M. leidyi exposed at oil concentration <=25 uL L(-1)
      after 6 days. Survival of ephyra and cydippid larva decreased with increasing
      crude oil concentration and exposition time. The median lethal concentration
      (LC50) for ephyra larvae ranged from 14.41 to 0.15 uL L(-1) after 1 and 3 days,
      respectively. LC50 for cydippid larvae ranged from 14.52 to 8.94 uL L(-1) after 3
      and 6 days, respectively. We observed selective bioaccumulation of chrysene,
      phenanthrene and pyrene in A. aurita and chrysene, pyrene, benzo[a]pyrene,
      benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]anthracene in M. leidyi.
      Overall, our results indicate that (1) A. aurita and M. leidyi adults had a high
      tolerance to crude oil exposure compared to other zooplankton, whereas P.
      noctiluca was highly sensitive to crude oil, (2) larval stages of gelatinous
      zooplankton were more sensitive to crude oil than adult stages, and (3) some of
      the most toxic PAHs of crude oil can be bioaccumulated in gelatinous zooplankton
      and potentially be transferred up the food web and contaminate apex predators. 

PMID- 24116005
TI  - A Kalman-filter based approach to identification of time-varying gene regulatory
      networks.
AB  - MOTIVATION: Conventional identification methods for gene regulatory networks
      (GRNs) have overwhelmingly adopted static topology models, which remains
      unchanged over time to represent the underlying molecular interactions of a
      biological system. However, GRNs are dynamic in response to physiological and
      environmental changes. Although there is a rich literature in modeling static or
      temporally invariant networks, how to systematically recover these temporally
      changing networks remains a major and significant pressing challenge. The purpose
      of this study is to suggest a two-step strategy that recovers time-varying GRNs.
      RESULTS: It is suggested in this paper to utilize a switching auto-regressive
      model to describe the dynamics of time-varying GRNs, and a two-step strategy is
      proposed to recover the structure of time-varying GRNs. In the first step, the
      change points are detected by a Kalman-filter based method. The observed time
      series are divided into several segments using these detection results; and each
      time series segment belonging to two successive demarcating change points is
      associated with an individual static regulatory network. In the second step,
      conditional network structure identification methods are used to reconstruct the
      topology for each time interval. This two-step strategy efficiently decouples the
      change point detection problem and the topology inference problem. Simulation
      results show that the proposed strategy can detect the change points precisely
      and recover each individual topology structure effectively. Moreover, computation
      results with the developmental data of Drosophila Melanogaster show that the
      proposed change point detection procedure is also able to work effectively in
      real world applications and the change point estimation accuracy exceeds other
      existing approaches, which means the suggested strategy may also be helpful in
      solving actual GRN reconstruction problem.

PMID- 24116006
TI  - Altered expression of two-pore domain potassium (K2P) channels in cancer.
AB  - Potassium channels have become a focus in cancer biology as they play roles in
      cell behaviours associated with cancer progression, including proliferation,
      migration and apoptosis. Two-pore domain (K2P) potassium channels are background
      channels which enable the leak of potassium ions from cells. As these channels
      are open at rest they have a profound effect on cellular membrane potential and
      subsequently the electrical activity and behaviour of cells in which they are
      expressed. The K2P family of channels has 15 mammalian members and already 4
      members of this family (K2P2.1, K2P3.1, K2P9.1, K2P5.1) have been implicated in
      cancer. Here we examine the expression of all 15 members of the K2P family of
      channels in a range of cancer types. This was achieved using the online cancer
      microarray database, Oncomine (www.oncomine.org). Each gene was examined across
      20 cancer types, comparing mRNA expression in cancer to normal tissue. This
      analysis revealed all but 3 K2P family members (K2P4.1, K2P16.1, K2P18.1) show
      altered expression in cancer. Overexpression of K2P channels was observed in a
      range of cancers including breast, leukaemia and lung while more cancers (brain,
      colorectal, gastrointestinal, kidney, lung, melanoma, oesophageal) showed
      underexpression of one or more channels. K2P1.1, K2P3.1, K2P12.1, were
      overexpressed in a range of cancers. While K2P1.1, K2P3.1, K2P5.1, K2P6.1, K2P7.1
      and K2P10.1 showed significant underexpression across the cancer types examined.
      This analysis supports the view that specific K2P channels may play a role in
      cancer biology. Their altered expression together with their ability to impact
      the function of other ion channels and their sensitivity to environmental stimuli
      (pO2, pH, glucose, stretch) makes understanding the role these channels play in
      cancer of key importance. 

PMID- 24116007
TI  - Genome-wide association study identifies major loci for carcass weight on BTA14
      in Hanwoo (Korean cattle).
AB  - This genome-wide association study (GWAS) was conducted to identify major loci
      that are significantly associated with carcass weight, and their effects, in
      order to provide increased understanding of the genetic architecture of carcass
      weight in Hanwoo. This genome-wide association study identified one major
      chromosome region ranging from 23 Mb to 25 Mb on chromosome 14 as being
      associated with carcass weight in Hanwoo. Significant Bonferroni-corrected genome
      wide associations (P<1.52*10(-6)) were detected for 6 Single Nucleotide
      Polymorphic (SNP) loci for carcass weight on chromosome 14. The most significant
      SNP was BTB-01280026 (P = 4.02*10(-11)), located in the 25 Mb region on Bos
      taurus autosome 14 (BTA14). The other 5 significant SNPs were Hapmap27934-BTC
      065223 (P = 4.04*10(-11)) in 25.2 Mb, BTB-01143580 (P = 6.35*10(-11)) in 24.3 Mb,
      Hapmap30932-BTC-011225 (P = 5.92*10(-10)) in 24.8 Mb, Hapmap27112-BTC-063342 (P =
      5.18*10(-9)) in 25.4 Mb, and Hapmap24414-BTC-073009 (P = 7.38*10(-8)) in 25.4 Mb,
      all on BTA 14. One SNP (BTB-01143580; P = 6.35*10(-11)) lies independently from
      the other 5 SNPs. The 5 SNPs that lie together showed a large Linkage
      disequilibrium (LD) block (block size of 553 kb) with LD coefficients ranging
      from 0.53 to 0.89 within the block. The most significant SNPs accounted for 6.73%
      to 10.55% of additive genetic variance, which is quite a large proportion of the
      total additive genetic variance. The most significant SNP (BTB-01280026; P =
      4.02*10(-11)) had 16.96 kg of allele substitution effect, and the second most
      significant SNP (Hapmap27934-BTC-065223; P = 4.04*10(-11)) had 18.06 kg of effect
      on carcass weight, which correspond to 44% and 47%, respectively, of the
      phenotypic standard deviation for carcass weight in Hanwoo cattle. Our results
      demonstrated that carcass weight was affected by a major Quantitative Trait Locus
      (QTL) with a large effect and by many SNPs with small effects that are normally
      distributed.

PMID- 24116008
TI  - Applying linear and non-linear methods for parallel prediction of volume of
      distribution and fraction of unbound drug.
AB  - Volume of distribution and fraction unbound are two key parameters in
      pharmacokinetics. The fraction unbound describes the portion of free drug in
      plasma that may extravasate, while volume of distribution describes the tissue
      access and binding of a drug. Reliable in silico predictions of these
      pharmacokinetic parameters would benefit the early stages of drug discovery, as
      experimental measuring is not feasible for screening purposes. We have applied
      linear and nonlinear multivariate approaches to predict these parameters: linear
      partial least square regression and non-linear recursive partitioning
      classification. The volume of distribution and fraction of unbound drug in plasma
      are predicted in parallel within the model, since the two are expected to be
      affected by similar physicochemical drug properties. Predictive models for both
      parameters were built and the performance of the linear models compared to models
      included in the commercial software Volsurf+. Our models performed better in
      predicting the unbound fraction (Q(2) 0.54 for test set compared to 0.38 with
      Volsurf+ model), but prediction accuracy of the volume of distribution was
      comparable to the Volsurf+ model (Q(2) of 0.70 for test set compared to 0.71 with
      Volsurf+ model). The nonlinear classification models were able to identify
      compounds with a high or low volume of distribution (sensitivity 0.81 and 0.71,
      respectively, for test set), while classification of fraction unbound was less
      successful. The interrelationship between the volume of distribution and fraction
      unbound is investigated and described in terms of physicochemical descriptors.
      Lipophilicity and solubility descriptors were found to have a high influence on
      both volume of distribution and fraction unbound, but with an inverse
      relationship. 

PMID- 24116009
TI  - The clinical effectiveness of patient initiated clinics for patients with chronic
      or recurrent conditions managed in secondary care: a systematic review.
AB  - BACKGROUND: Missed or inappropriate hospital appointments cost the UK National
      Health Service millions of pounds each year and delay treatment for other
      patients. Innovative methods of appointment scheduling that are more flexible to
      patient needs, may improve service quality and preserve resources. METHODS: A
      systematic review of the evidence for the clinical effectiveness of patient
      initiated clinics in managing long term care for people with chronic or recurrent
      conditions in secondary care. Seven databases were searched including MEDLINE,
      Embase and PsycINFO (using the OVID interface), the Cochrane Library of
      Systematic Reviews and CENTRAL, Science Citation Index Expanded, Social Sciences
      Citation Index, and Conference Proceedings Citation Index (via the Web of Science
      interface) from inception to June 2013. Studies comparing patient initiated
      clinics with traditional consultant-led clinics in secondary care for people with
      long term chronic or recurrent diseases were included. Included studies had to
      provide data on clinical or resource use outcomes. Data were extracted and
      checked by two reviewers using a piloted, standardised data extraction form.
      RESULTS: Eight studies (n = 1927 individuals) were included. All were conducted
      in the UK. There were few significant differences in clinical outcomes between
      the intervention and control groups. In some instances, using the patient
      initiated clinics model was associated with savings in time and resource use. The
      risk of harm from using the patient initiated clinic model of organising
      outpatient care is low. Studies with longer follow-up periods are needed to
      assess the long term costs and the ongoing risk of potential harms. CONCLUSIONS:
      The UK policy context is ripe for evidence-based, patient-centred services to be
      implemented, especially where the use of health care resources can be optimised
      without reducing the quality of care. Implementation of patient initiated clinics
      should remain cautious, with importance placed on ongoing evaluation of long term
      outcomes and costs.

PMID- 24116010
TI  - Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.
AB  - BACKGROUND: A common pattern emerging from several studies evaluating the impact
      of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm) conducted in countries
      worldwide is the low attack rate observed in elderly compared to that observed in
      children and young adults. The biological or social mechanisms responsible for
      the observed age-specific risk of infection are still to be deeply investigated.
      METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic
      sera was determined using left over sera taken for diagnostic purposes or routine
      ascertainment obtained from clinical laboratories. The antibody titres were
      measured by the haemagglutination inhibition (HI) assay. To investigate whether
      certain age groups had higher risk of infection the presence of protective
      antibody (>=1?40), was calculated using exact binomial 95% CI on both pre- and
      post- pandemic serological data in the age groups considered. To estimate age
      specific susceptibility to infection we used an age-structured SEIR model.
      RESULTS: By comparing pre- and post-pandemic serological data in Italy we found
      age- specific attack rates similar to those observed in other countries.
      Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was
      estimated to be 16.3% (95% CI 9.4%-23.1%). Modeling results allow ruling out the
      hypothesis that only age-specific characteristics of the contact network and
      levels of pre-pandemic immunity are responsible for the observed age-specific
      risk of infection. This means that age-specific susceptibility to infection,
      suspected to play an important role in the pandemic, was not only determined by
      pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results
      claim for new studies to better identify the biological mechanisms, which might
      have determined the observed pattern of susceptibility with age. Moreover, our
      results highlight the need to obtain early estimates of differential
      susceptibility with age in any future pandemics to obtain more reliable real time
      estimates of critical epidemiological parameters.

PMID- 24116011
TI  - The long-term dynamics of mortality benefits from improved water and sanitation
      in less developed countries.
AB  - The problem of inadequate access to water, sanitation and hygiene (WASH) in less
      developed nations has received much attention over the last several decades (most
      recently in the Millennium Development Goals), largely because diseases
      associated with such conditions contribute substantially to mortality in poor
      countries. We present country-level projections for WASH coverage and for WASH
      related mortality in developing regions over a long time horizon (1975-2050) and
      provide dynamic estimates of the economic value of potential reductions in this
      WASH-related mortality, which go beyond the static results found in previous
      work. Over the historical period leading up to the present, our analysis shows
      steady and substantial improvements in WASH coverage and declining mortality
      rates across many developing regions, namely East Asia and the Pacific, Latin
      America and the Caribbean, Eastern Europe and the Middle East. The economic value
      of potential health gains from eliminating mortality attributable to poor water
      and sanitation has decreased substantially, and in the future will therefore be
      modest in these regions. Where WASH-related deaths remain high (in parts of South
      Asia and much of Sub-Saharan Africa), if current trends continue, it will be
      several decades before economic development and investments in improved water and
      sanitation will result in the capture of these economic benefits. The fact that
      health losses will likely remain high in these two regions over the medium term
      suggests that accelerated efforts are needed to improve access to water and
      sanitation, though the costs and benefits of such efforts in specific locations
      should be carefully assessed. 

PMID- 24116012
TI  - PALSAR 50 m mosaic data based national level biomass estimation in Cambodia for
      implementation of REDD+ mechanism.
AB  - Tropical countries like Cambodia require information about forest biomass for
      successful implementation of climate change mitigation mechanism related to
      Reducing Emissions from Deforestation and forest Degradation (REDD+). This study
      investigated the potential of Phased Array-type L-band Synthetic Aperture Radar
      Fine Beam Dual (PALSAR FBD) 50 m mosaic data to estimate Above Ground Biomass
      (AGB) in Cambodia. AGB was estimated using a bottom-up approach based on field
      measured biomass and backscattering (sigma(o)) properties of PALSAR data. The
      relationship between the PALSAR sigma(o) HV and HH/HV with field measured biomass
      was strong with R(2) = 0.67 and 0.56, respectively. PALSAR estimated AGB show
      good results in deciduous forests because of less saturation as compared to dense
      evergreen forests. The validation results showed a high coefficient of
      determination R(2) = 0.61 with RMSE  = 21 Mg/ha using values up to 200 Mg/ha
      biomass. There were some uncertainties because of the uncertainty in the field
      based measurement and saturation of PALSAR data. AGB map of Cambodian forests
      could be useful for the implementation of forest management practices for REDD+
      assessment and policies implementation at the national level. 

PMID- 24116014
TI  - PKCalpha-specific phosphorylation of the troponin complex in human myocardium: a
      functional and proteomics analysis.
AB  - AIMS: Protein kinase Calpha (PKCalpha) is one of the predominant PKC isoforms
      that phosphorylate cardiac troponin. PKCalpha is implicated in heart failure and
      serves as a potential therapeutic target, however, the exact consequences for
      contractile function in human myocardium are unclear. This study aimed to
      investigate the effects of PKCalpha phosphorylation of cardiac troponin (cTn) on
      myofilament function in human failing cardiomyocytes and to resolve the potential
      targets involved. METHODS AND RESULTS: Endogenous cTn from permeabilized
      cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was
      exchanged (~69%) with PKCalpha-treated recombinant human cTn (cTn (DD+PKCalpha)).
      This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in
      vitro cross-phosphorylation of the PKA sites by PKCalpha. Isometric force was
      measured at various [Ca(2+)] after exchange. The maximal force (Fmax) in the cTn
      (DD+PKCalpha) group (17.1+/-1.9 kN/m(2)) was significantly reduced compared to
      the cTn (DD) group (26.1+/-1.9 kN/m(2)). Exchange of endogenous cTn with cTn
      (DD+PKCalpha) increased Ca(2+)-sensitivity of force (pCa50 = 5.59+/-0.02)
      compared to cTn (DD) (pCa50 = 5.51+/-0.02). In contrast, subsequent PKCalpha
      treatment of the cells exchanged with cTn (DD+PKCalpha) reduced pCa50 to 5.45+/
      0.02. Two PKCalpha-phosphorylated residues were identified with mass
      spectrometry: Ser198 on cTnI and Ser179 on cTnT, although phosphorylation of
      Ser198 is very low. Using mass spectrometry based-multiple reaction monitoring,
      the extent of phosphorylation of the cTnI sites was quantified before and after
      treatment with PKCalpha and showed the highest phosphorylation increase on
      Thr143. CONCLUSION: PKCalpha-mediated phosphorylation of the cTn complex
      decreases Fmax and increases myofilament Ca(2+)-sensitivity, while subsequent
      treatment with PKCalpha in situ decreased myofilament Ca(2+)-sensitivity. The
      known PKC sites as well as two sites which have not been previously linked to
      PKCalpha are phosphorylated in human cTn complex treated with PKCalpha with a
      high degree of specificity for Thr143.

PMID- 24116015
TI  - Serum glycan markers for evaluation of disease activity and prediction of
      clinical course in patients with ulcerative colitis.
AB  - BACKGROUND: The aims of this study were to determine the change of whole-serum N
      glycan profile in ulcerative colitis (UC) patients and to investigate its
      clinical utility. METHODS: We collected serum from 75 UC patients at the time of
      admission and the same number of age/sex-matched healthy volunteers. Serum glycan
      profile was measured by comprehensive quantitative high-throughput glycome
      analysis and was compared with disease activity and prognosis. RESULTS: Out of 61
      glycans detected, 24 were differentially expressed in UC patients. Pathway
      analysis demonstrated that highly sialylated multi-branched glycans and
      agalactosyl bi-antennary glycans were elevated in UC patients; in addition, the
      glycan ratio m/z 2378/1914, which also increased in UC, showed the highest Area
      under Receiver Operating Characteristic curve (0.923) for the diagnosis of UC.
      Highly sialylated multi-branched glycans and the glycan ratio m/z 2378/1914 were
      higher in the patients with total colitis, Clinical Activity Index >10, Mayo
      endoscopic score 3, or a steroid-refractory status. In particular, the glycan
      ratio m/z 2378/1914 (above median) was an independent prognostic factor for the
      need for an operation (hazard ratio, 2.67; 95% confidence interval, 1.04-7.84).
      CONCLUSIONS: Whole-serum glycan profiles revealed that the glycan ratio m/z
      2378/1914 and highly sialylated multi-branched glycans increase in UC patients,
      and are correlated with disease activity. The glycan ratio m/z 2378/1914 was an
      independent predictive factor of the prognosis of UC.

PMID- 24116013
TI  - Dysregulation of complement system and CD4+ T cell activation pathways implicated
      in allergic response.
AB  - Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell
      activation. Here we propose a novel methodology to gain insight into how
      coordinated behaviour emerges between disease-dysregulated pathways in response
      to pathophysiological stimuli. Using peripheral blood mononuclear cells of
      allergic rhinitis patients and controls cultured with and without pollen
      allergens, we integrate CD4+ T cell gene expression from microarray data and
      genetic markers of allergic sensitisation from GWAS data at the pathway level
      using enrichment analysis; implicating the complement system in both cellular and
      systemic response to pollen allergens. We delineate a novel disease network
      linking T cell activation to the complement system that is significantly enriched
      for genes exhibiting correlated gene expression and protein-protein interactions,
      suggesting a tight biological coordination that is dysregulated in the disease
      state in response to pollen allergen but not to diluent. This novel disease
      network has high predictive power for the gene and protein expression of the Th2
      cytokine profile (IL-4, IL-5, IL-10, IL-13) and of the Th2 master regulator
      (GATA3), suggesting its involvement in the early stages of CD4+ T cell
      differentiation. Dissection of the complement system gene expression identifies 7
      genes specifically associated with atopic response to pollen, including C1QR1,
      CFD, CFP, ITGB2, ITGAX and confirms the role of C3AR1 and C5AR1. Two of these
      genes (ITGB2 and C3AR1) are also implicated in the network linking complement
      system to T cell activation, which comprises 6 differentially expressed genes.
      C3AR1 is also significantly associated with allergic sensitisation in GWAS data. 

PMID- 24116016
TI  - Defluorination of aqueous perfluorooctanesulfonate by activated persulfate
      oxidation.
AB  - Activated persulfate oxidation technologies based on sulfate radicals were first
      evaluated for defluorination of aqueous perfluorooctanesulfonate (PFOS). The
      influences of catalytic method, time, pH and K2S2O8 amounts on PFOS
      defluorination were investigated. The intermediate products during PFOS
      defluorination were detected by using LC/MS/MS. The results showed that the S2O8
      (2-) had weak effect on the defluorination of PFOS, while the PFOS was
      oxidatively defluorinated by sulfate radicals in water. The defluorination
      efficiency of PFOS under various treatment was followed the order: HT
      (hydrothermal)/K2S2O8 > UV (ultraviolet)/K2S2O8 > Fe(2+)/K2S2O8 > US
      (ultrasound)/K2S2O8. Low pH was favorable for the PFOS defluorination with
      sulfate radicals. Increase in the amount of S2O8 (2-) had positive effect on PFOS
      defluorination. However, further increase in amounts of S2O8 (2-) caused
      insignificant improvement in PFOS defluorination due to elimination of sulfate
      radicals under high concentration of S2O8 (2-). CF3(CF2)nCOOH (n = 0-6) were
      detected as intermediates during PFOS defluorination. Sulfate radicals oxidation
      and hydrolysis were the main mechanisms involved in defluorination process of
      PFOS. 

PMID- 24116017
TI  - Methane-carbon flow into the benthic food web at cold seeps--a case study from
      the Costa Rica subduction zone.
AB  - Cold seep ecosystems can support enormous biomasses of free-living and symbiotic
      chemoautotrophic organisms that get their energy from the oxidation of methane or
      sulfide. Most of this biomass derives from animals that are associated with
      bacterial symbionts, which are able to metabolize the chemical resources provided
      by the seeping fluids. Often these systems also harbor dense accumulations of non
      symbiotic megafauna, which can be relevant in exporting chemosynthetically fixed
      carbon from seeps to the surrounding deep sea. Here we investigated the carbon
      sources of lithodid crabs (Paralomis sp.) feeding on thiotrophic bacterial mats
      at an active mud volcano at the Costa Rica subduction zone. To evaluate the
      dietary carbon source of the crabs, we compared the microbial community in
      stomach contents with surface sediments covered by microbial mats. The stomach
      content analyses revealed a dominance of epsilonproteobacterial 16S rRNA gene
      sequences related to the free-living and epibiotic sulfur oxidiser Sulfurovum sp.
      We also found Sulfurovum sp. as well as members of the genera Arcobacter and
      Sulfurimonas in mat-covered surface sediments where Epsilonproteobacteria were
      highly abundant constituting 10% of total cells. Furthermore, we detected
      substantial amounts of bacterial fatty acids such as i-C15?0 and C17?1omega6c
      with stable carbon isotope compositions as low as -530/00 in the stomach and
      muscle tissue. These results indicate that the white microbial mats at Mound 12
      are comprised of Epsilonproteobacteria and that microbial mat-derived carbon
      provides an important contribution to the crab's nutrition. In addition, our
      lipid analyses also suggest that the crabs feed on other (13)C-depleted organic
      matter sources, possibly symbiotic megafauna as well as on photosynthetic carbon
      sources such as sedimentary detritus. 

PMID- 24116018
TI  - Synconset waves and chains: spiking onsets in synchronous populations predict and
      are predicted by network structure.
AB  - Synfire waves are propagating spike packets in synfire chains, which are
      feedforward chains embedded in random networks. Although synfire waves have
      proved to be effective quantification for network activity with clear relations
      to network structure, their utilities are largely limited to feedforward networks
      with low background activity. To overcome these shortcomings, we describe a novel
      generalisation of synfire waves, and define 'synconset wave' as a cascade of
      first spikes within a synchronisation event. Synconset waves would occur in
      'synconset chains', which are feedforward chains embedded in possibly heavily
      recurrent networks with heavy background activity. We probed the utility of
      synconset waves using simulation of single compartment neuron network models with
      biophysically realistic conductances, and demonstrated that the spread of
      synconset waves directly follows from the network connectivity matrix and is
      modulated by top-down inputs and the resultant oscillations. Such synconset
      profiles lend intuitive insights into network organisation in terms of connection
      probabilities between various network regions rather than an adjacency matrix. To
      test this intuition, we develop a Bayesian likelihood function that quantifies
      the probability that an observed synfire wave was caused by a given network.
      Further, we demonstrate it's utility in the inverse problem of identifying the
      network that caused a given synfire wave. This method was effective even in
      highly subsampled networks where only a small subset of neurons were accessible,
      thus showing it's utility in experimental estimation of connectomes in real
      neuronal-networks. Together, we propose synconset chains/waves as an effective
      framework for understanding the impact of network structure on function, and as a
      step towards developing physiology-driven network identification methods.
      Finally, as synconset chains extend the utilities of synfire chains to arbitrary
      networks, we suggest utilities of our framework to several aspects of network
      physiology including cell assemblies, population codes, and oscillatory
      synchrony. 

PMID- 24116019
TI  - Bacterial community mapping of the mouse gastrointestinal tract.
AB  - Keeping mammalian gastrointestinal (GI) tract communities in balance is crucial
      for host health maintenance. However, our understanding of microbial communities
      in the GI tract is still very limited. In this study, samples taken from the GI
      tracts of C57BL/6 mice were subjected to 16S rRNA gene sequence-based analysis to
      examine the characteristic bacterial communities along the mouse GI tract,
      including those present in the stomach, duodenum, jejunum, ileum, cecum, colon
      and feces. Further analyses of the 283,234 valid sequences obtained from
      pyrosequencing revealed that the gastric, duodenal, large intestinal and fecal
      samples had higher phylogenetic diversity than the jejunum and ileum samples did.
      The microbial communities found in the small intestine and stomach were different
      from those seen in the large intestine and fecal samples. A greater proportion of
      Lactobacillaceae were found in the stomach and small intestine, while a larger
      proportion of anaerobes such as Bacteroidaceae, Prevotellaceae, Rikenellaceae,
      Lachnospiraceae, and Ruminococcaceae were found in the large intestine and feces.
      In addition, inter-mouse variations of microbiota were observed between the large
      intestinal and fecal samples, which were much smaller than those between the
      gastric and small intestinal samples. As far as we can ascertain, ours is the
      first study to systematically characterize bacterial communities from the GI
      tracts of C57BL/6 mice. 

PMID- 24116020
TI  - Expression of advanced glycation end-products on sun-exposed and non-exposed
      cutaneous sites during the ageing process in humans.
AB  - The glycation process is involved in both the intrinsic (individual, genetic) and
      extrinsic (ultraviolet light, polution and lifestyle) aging processes, and can be
      quantified at the epidermal or dermal level by histological, immunohistochemical
      (IHC), or imagistic methods. Our study is focused on a histological and
      immunohistological comparison of sun-protected regions versus sun-exposed regions
      from different age groups of skin phototype III subjects, related to the aging
      process. Skin samples collected from non-protected and UV protected regions of
      four experimental groups with different ages, were studied using histology and
      IHC methods for AGE-CML [N(epsilon)-(carboxymethyl)lysine]. A semi-quantitative
      assessment of the CML expression in the microvascular endothelium and dermal
      fibroblasts was performed. The Pearson one-way ANOVA was used to compare data
      between the groups. In the dermis of sun-exposed skin, the number and the
      intensity of CML positive cells in both fibroblasts and endothelial cells
      (p<0.05) was higher compared to sun-protected skin, and was significantly
      increased in older patients. The sun-exposed areas had a more than 10% higher AGE
      CML score than the protected areas. No statistically significant correlation was
      observed between the histological score and the IHC expression of CML. We
      concluded that in healthy integument, the accumulation of final glycation
      products increases with age and is amplified by ultraviolet exposure. The study
      provides new knowledge on differences of AGE-CML between age groups and protected
      and unprotected areas and emphasizes that endothelium and perivascular area are
      most affected, justifying combined topical and systemic therapies. 

PMID- 24116021
TI  - Comparative toxicity assessment of nanosilver on three Daphnia species in acute,
      chronic and multi-generation experiments.
AB  - The antibacterial properties of nanosilver have led to a versatile application
      spectrum including medical purposes and personal care products. However, the
      increasing use of nanosilver has raised concerns about its environmental impacts.
      Long-term exposure studies with aquatic invertebrates are essential to assess
      possible adverse effects on aquatic ecosystems. In the present study, acute (48
      h), chronic (21 d) and long-term effects of nanosilver (primary size 15 nm) on
      five successive generations of three Daphnia species (D. magna, D. pulex, and D.
      galeata) were investigated. Acute EC50 values of nanosilver were 121 ug Ag L(-1)
      for D. magna being the least sensitive species and 8.95 and 13.9 ug Ag L(-1) for
      D. pulex and D. galeata, respectively. Chronic exposure provided EC10 values of
      0.92 ug Ag L(-1) for D. magna showing the most sensitive chronic reaction and
      2.25 and 3.45 ug Ag L(-1) for D. pulex and D. galeata, respectively. Comparative
      exposure to AgNO3 revealed a generally higher toxicity of the soluble form of
      silver. The multi-generation experiments resulted in effects on the population
      level for all tested species. Exposure of D. magna indicated an increased
      toxicity of nanosilver in the fifth generation of animals exposed to 10 ug Ag L(
      1). Neonates from pre-exposed parental daphnids did not completely recover when
      transferred into clean water. Exposure of D. pulex and D. galeata revealed not
      only increasing toxicity in some generations, but also greater tolerance to
      nanosilver. This study contributes to the assessment of the risk potential of
      nanosilver on aquatic ecosystems. It shows that effects of nanosilver vary within
      one genus and change with exposure duration. Therefore, long-term studies
      considering different aquatic species are needed to better understand the
      possible effects of nanosilver on aquatic ecosystems. 

PMID- 24116022
TI  - Future bloom and blossom frost risk for Malus domestica considering climate model
      and impact model uncertainties.
AB  - The future bloom and risk of blossom frosts for Malus domestica were projected
      using regional climate realizations and phenological ( = impact) models. As
      climate impact projections are susceptible to uncertainties of climate and impact
      models and model concatenation, the significant horizon of the climate impact
      signal was analyzed by applying 7 impact models, including two new developments,
      on 13 climate realizations of the IPCC emission scenario A1B. Advancement of
      phenophases and a decrease in blossom frost risk for Lower Saxony (Germany) for
      early and late ripeners was determined by six out of seven phenological models.
      Single model/single grid point time series of bloom showed significant trends by
      2021-2050 compared to 1971-2000, whereas the joint signal of all climate and
      impact models did not stabilize until 2043. Regarding blossom frost risk, joint
      projection variability exceeded the projected signal. Thus, blossom frost risk
      cannot be stated to be lower by the end of the 21st century despite a negative
      trend. As a consequence it is however unlikely to increase. Uncertainty of
      temperature, blooming date and blossom frost risk projection reached a minimum at
      2078-2087. The projected phenophases advanced by 5.5 d K(-1), showing partial
      compensation of delayed fulfillment of the winter chill requirement and faster
      completion of the following forcing phase in spring. Finally, phenological model
      performance was improved by considering the length of day. 

PMID- 24116023
TI  - Aerobic degradation of N-methyl-4-nitroaniline (MNA) by Pseudomonas sp. strain
      FK357 isolated from soil.
AB  - N-Methyl-4-nitroaniline (MNA) is used as an additive to lower the melting
      temperature of energetic materials in the synthesis of insensitive explosives.
      Although the biotransformation of MNA under anaerobic condition has been
      reported, its aerobic microbial degradation has not been documented yet. A soil
      microcosms study showed the efficient aerobic degradation of MNA by the
      inhabitant soil microorganisms. An aerobic bacterium, Pseudomonas sp. strain
      FK357, able to utilize MNA as the sole carbon, nitrogen, and energy source, was
      isolated from soil microcosms. HPLC and GC-MS analysis of the samples obtained
      from growth and resting cell studies showed the formation of 4-nitroaniline (4
      NA), 4-aminophenol (4-AP), and 1, 2, 4-benzenetriol (BT) as major metabolic
      intermediates in the MNA degradation pathway. Enzymatic assay carried out on cell
      free lysates of MNA grown cells confirmed N-demethylation reaction is the first
      step of MNA degradation with the formation of 4-NA and formaldehyde products.
      Flavin-dependent transformation of 4-NA to 4-AP in cell extracts demonstrated
      that the second step of MNA degradation is a monooxygenation. Furthermore,
      conversion of 4-AP to BT by MNA grown cells indicates the involvement of
      oxidative deamination (release of NH2 substituent) reaction in third step of MNA
      degradation. Subsequent degradation of BT occurs by the action of benzenetriol 1,
      2-dioxygenase as reported for the degradation of 4-nitrophenol. This is the first
      report on aerobic degradation of MNA by a single bacterium along with elucidation
      of metabolic pathway. 

PMID- 24116024
TI  - Robotic partial nephrectomy for renal tumors larger than 4 cm: a systematic
      review and meta-analysis.
AB  - BACKGROUND: With the establishment of minimally invasive surgery in society, the
      robot has been increasingly widely used in the urologic field, including in
      partial nephrectomy. This study aimed to comprehensively summarize the currently
      available evidence on the feasibility and safety of robotic partial nephrectomy
      for renal tumors of >4 cm. METHOD AND FINDINGS: An electronic database search of
      PubMed, Scopus, Web of Science, and the Cochrane Library was performed. This
      systematic review and meta-analysis was based on all relevant studies that
      assessed robotic partial nephrectomy for renal tumors of >4 cm. Five studies were
      included. The meta-analysis involved 3 studies from 11 institutions including 154
      patients, while the narrative review involved the remaining 2 studies from 5
      institutions including 64 patients. In the meta-analysis, the mean ischemic time,
      operation time, and console time was 28, 319, and 189 minutes, respectively. The
      estimated blood loss and length of stay was 317 ml and 3.8 days, respectively.
      The rates of conversion, positive margins, intraoperative complications,
      postoperative complications, hilar clamping, and collecting system repair were
      7.0%, 3.5%, 7.0%, 9.8%, 93.9%, and 47.5%, respectively. The narrative review
      showed results similar to those of the meta-analysis. CONCLUSIONS: Robotic
      partial nephrectomy is feasible and safe for renal tumors of >4 cm with an
      acceptable warm ischemic time, positive margin rate, conversion rate,
      complication rate, operation time, estimated blood loss, and length of stay.

PMID- 24116025
TI  - Genomic adaptation of the Lactobacillus casei group.
AB  - Lactobacillus casei, L. paracasei, and L. rhamnosus form a closely related
      taxonomic group (Lactobacillus casei group) within the facultatively
      heterofermentative lactobacilli. Here, we report the complete genome sequences of
      L. paracasei JCM 8130 and L. casei ATCC 393, and the draft genome sequence of L.
      paracasei COM0101, all of which were isolated from daily products. Furthermore,
      we re-annotated the genome of L. rhamnosus ATCC 53103 (also known as L. rhamnosus
      GG), which we have previously reported. We confirmed that ATCC 393 is distinct
      from other strains previously described as L. paracasei. The core genome of 10
      completely sequenced strains of the L. casei group comprised 1,682 protein-coding
      genes. Although extensive genome-wide synteny was found among the L. casei group,
      the genomes of ATCC 53103, JCM 8130, and ATCC 393 contained genomic islands
      compared with L. paracasei ATCC 334. Several genomic islands, including
      carbohydrate utilization gene clusters, were found at the same loci in the
      chromosomes of the L. casei group. The spaCBA pilus gene cluster, which was first
      identified in GG, was also found in other strains of the L. casei group, but
      several L. paracasei strains including COM0101 contained truncated spaC gene.
      ATCC 53103 encoded a higher number of proteins involved in carbohydrate
      utilization compared with intestinal lactobacilli, and extracellular adhesion
      proteins, several of which are absent in other strains of the L. casei group. In
      addition to previously fully sequenced L. rhamnosus and L. paracasei strains, the
      complete genome sequences of L. casei will provide valuable insights into the
      evolution of the L. casei group. 

PMID- 24116026
TI  - Effects of pulse current on endurance exercise and its anti-fatigue properties in
      the hepatic tissue of trained rats.
AB  - Fatigue is synonymous with a wide spectrum of familiar physiological conditions,
      from pathology and general health, to sport and physical exercise. Strenuous,
      prolonged exercise training causes fatigue. Although several studies have
      investigated the effects of electrical stimulation frequency on muscle fatigue,
      the effects of percutaneous pulse current stimulation on fatigue in the hepatic
      tissue of trained rats is still unclear. In order to find an effective strategy
      to prevent fatigue or enhance recovery, the effects of pulse current on endurance
      exercise and its anti-fatigue properties in exercised rats were studied. Rats
      were subjected to one, three or five weeks of swimming exercise training. After
      exercise training, rats in the treated group received daily applications of pulse
      current. All rats were sacrificed after one, three or five weeks of swimming
      exercise, and the major biochemical indexes were measured in serum and liver. The
      results demonstrate that pulse current could prolong the exhaustion swimming
      time, as well as decrease serum ALT, AST and LD levels and liver MDA content. It
      also elevated serum LDH activity, liver SOD activity and glycogen content.
      Furthermore, pulse current increased the expression of Bcl-2 and decreased the
      expression of Bax. Taken together, these results show that pulse current can
      elevate endurance capacity and facilitate recovery from fatigue. 

PMID- 24116027
TI  - The tight-junction protein claudin-6 induces epithelial differentiation from
      mouse F9 and embryonic stem cells.
AB  - During epithelialization, cell adhesions and polarity must be established to
      maintain tissue assemblies and separate the biological compartments in the body.
      However, the molecular basis of epithelial morphogenesis, in particular, a role
      of cell adhesion molecules in epithelial differentiation from stem cells, remains
      unclear. Here, we show that the stable and conditional expression of a tight
      junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse
      F9 stem cells. We also demonstrate that Cldn6 induces the expression of other
      tight-junction and microvillus molecules including Cldn7, occludin, ZO-1alpha+,
      and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by
      attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium
      Perfringens enterotoxin. Furthermore, similar results were obtained in mouse
      embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel
      cue to induce epithelial differentiation. 

PMID- 24116028
TI  - A systematic review of systematic reviews and panoramic meta-analysis: staples
      versus sutures for surgical procedures.
AB  - OBJECTIVE: To systematically evaluate the evidence across surgical specialties as
      to whether staples or sutures better improve patient and provider level outcomes.
      DESIGN: A systematic review of systematic reviews and panoramic meta-analysis of
      pooled estimates. RESULTS: Eleven systematic reviews, including 13,661
      observations, met the inclusion criteria. In orthopaedic surgery sutures were
      found to be preferable, and for appendicial stump sutures were protective against
      both surgical site infection and post surgical complications. However, staples
      were protective against leak in ilecolic anastomosis. For all other surgery types
      the evidence was inconclusive with wider confidence intervals including the
      possibly of preferential outcomes for surgical site infection or post surgical
      complication for either staples or sutures. Whilst reviews showed substantial
      variation in mean differences in operating time (I(2) 94%) there was clear
      evidence of a reduction in average operating time across all surgery types. Few
      reviews reported on length of stay, but the three reviews that did (I(2) 0%,
      including 950 observations) showed a non significant reduction in length of stay,
      but showed evidence of publication bias (P-value for Egger test 0.05).
      CONCLUSIONS: Evidence across surgical specialties indicates that wound closure
      with staples reduces the mean operating time. Despite including several thousand
      observations, no clear evidence of superiority emerged for either staples or
      sutures with respect to surgical site infection, post surgical complications, or
      length of stay.

PMID- 24116029
TI  - Efficacy of Olyset(r) Plus, a new long-lasting insecticidal net incorporating
      permethrin and piperonyl-butoxide against multi-resistant malaria vectors
      [corrected].
AB  - Due to the rapid extension of pyrethroid resistance in malaria vectors worldwide,
      manufacturers are developing new vector control tools including insecticide
      mixtures containing at least two active ingredients with different mode of action
      as part of insecticide resistance management. Olyset(r) Plus is a new long
      lasting insecticidal net (LLIN) incorporating permethrin and a synergist,
      piperonyl butoxide (PBO), into its fibres in order to counteract metabolic-based
      pyrethroid resistance of mosquitoes. In this study, we evaluated the efficacy of
      Olyset(r) Plus both in laboratory and field against susceptible and multi
      resistant malaria vectors and compared with Olyset Net, which is a permethrin
      incorporated into polyethylene net. In laboratory, Olyset(r) Plus performed
      better than Olyset(r) Net against susceptible Anopheles gambiae strain with a 2
      day regeneration time owing to an improved permethrin bleeding rate with the new
      incorporation technology. It also performed better than Olyset(r) Net against
      multiple resistant populations of An. gambiae in experimental hut trials in West
      Africa. Moreover, the present study showed evidence for a benefit of
      incorporating a synergist, PBO, with a pyrethroid insecticide into mosquito
      netting. These results need to be further validated in a large-scale field trial
      to assess the durability and acceptability of this new tool for malaria vector
      control. 

PMID- 24116030
TI  - Detection of homologous recombination events in bacterial genomes.
AB  - We study the detection of mutations, sequencing errors, and homologous
      recombination events (HREs) in a set of closely related microbial genomes. We
      base the model on single nucleotide polymorphisms (SNPs) and break the genomes
      into blocks to handle the rearrangement problem. Then we apply a dynamic
      programming algorithm to model whether changes within each block are likely a
      result of mutations, sequencing errors, or HREs. Results from simulation
      experiments show that we can detect 31%-61% of HREs and the precision of our
      detection is about 48%-90% depending on the rates of mutation and missing data.
      The HREfinder software for predicting HREs in a set of whole genomes is available
      as open source (http://sourceforge.net/projects/hrefinder/). 

PMID- 24116031
TI  - Epigenetic priming of AML blasts for all-trans retinoic acid-induced
      differentiation by the HDAC class-I selective inhibitor entinostat.
AB  - All-trans retinoic acid (ATRA) has only limited single agent activity in AML
      without the PML-RARalpha fusion (non-M3 AML). In search of a sensitizing strategy
      to overcome this relative ATRA resistance, we investigated the potency of the
      HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60
      and primary AML blasts. Entinostat alone induced robust differentiation of both
      cell lines, which was enhanced by the combination with ATRA. This "priming"
      effect on ATRA-induced differentiation was at least equivalent to that achieved
      with the DNA hypomethylating agent decitabine, and could overall be recapitulated
      in primary AML blasts treated ex vivo. Moreover, entinostat treatment established
      the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of
      the RARbeta2 gene, an essential mediator of retinoic acid (RA) signaling in
      different solid tumor models. Similarly, RARbeta2 promoter hypermethylation
      (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent)
      could be partially reversed by decitabine in the two cell lines. Re-induction of
      the epigenetically silenced RARbeta2 gene was achieved only when entinostat or
      decitabine were given prior to ATRA treatment. Thus in this model, reactivation
      of RARbeta2 was not necessarily required for the differentiation effect, and
      pharmacological RARbeta2 promoter demethylation may be a bystander phenomenon
      rather than an essential prerequisite for the cellular effects of decitabine when
      combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to
      the differentiation-inducing effects of ATRA, entinostat is at least as active as
      decitabine, and both act in part independently from RARbeta2. Further
      investigation of this treatment combination in non-M3 AML patients is therefore
      warranted, independently of RARbeta2 gene silencing by DNA methylation. 

PMID- 24116033
TI  - Life cycle analysis of kidney gene expression in male F344 rats.
AB  - Age is a predisposing condition for susceptibility to chronic kidney disease and
      progression as well as acute kidney injury that may arise due to the adverse
      effects of some drugs. Age-related differences in kidney biology, therefore, are
      a key concern in understanding drug safety and disease progression. We
      hypothesize that the underlying suite of genes expressed in the kidney at various
      life cycle stages will impact susceptibility to adverse drug reactions.
      Therefore, establishing changes in baseline expression data between these life
      stages is the first and necessary step in evaluating this hypothesis. Untreated
      male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age.
      Kidneys were collected for histology and gene expression analysis. Agilent whole
      genome rat microarrays were used to query global expression profiles. An ANOVA
      (p<0.01) coupled with a fold-change>1.5 in relative mRNA expression, was used to
      identify 3,724 unique differentially expressed genes (DEGs). Principal component
      analyses of these DEGs revealed three major divisions in life-cycle renal gene
      expression. K-means cluster analysis identified several groups of genes that
      shared age-specific patterns of expression. Pathway analysis of these gene groups
      revealed age-specific gene networks and functions related to renal function and
      aging, including extracellular matrix turnover, immune cell response, and renal
      tubular injury. Large age-related changes in expression were also demonstrated
      for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and
      Tff3. These results suggest specific groups of genes that may underlie age
      specific susceptibilities to adverse drug reactions and disease. This analysis of
      the basal gene expression patterns of renal genes throughout the life cycle of
      the rat will improve the use of current and future renal biomarkers and inform
      our assessments of kidney injury and disease. 

PMID- 24116032
TI  - Mast cell stabilization alleviates acute lung injury after orthotopic autologous
      liver transplantation in rats by downregulating inflammation.
AB  - BACKGROUND: Acute lung injury (ALI) is one of the most severe complications after
      orthotopic liver transplantation. Amplified inflammatory response after
      transplantation contributes to the process of ALI, but the mechanism underlying
      inflammation activation is not completely understood. We have demonstrated that
      mast cell stabilization attenuated inflammation and ALI in a rodent intestine
      ischemia/reperfusion model. We hypothesized that upregulation of inflammation
      triggered by mast cell activation may be involve in ALI after liver
      transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic
      autologous liver transplantation (OALT) and were executed 4, 8, 16, and 24 h
      after OALT. The rats were pretreated with the mast cell stabilizers cromolyn
      sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues
      and arterial blood were collected to evaluate lung injury. beta-hexosaminidase
      and mast cell tryptase levels were assessed to determine the activation of mast
      cells. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6
      in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay.
      Nuclear factor-kappa B (NF-kappaB) p65 translocation was assessed by Western
      blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage
      with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor
      surfactant protein C levels, which corresponded to the significant elevation of
      pro-inflammatory cytokines, beta-hexosaminidase, and tryptase levels in serum and
      lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast
      cell stabilization significantly inhibited the activation of mast cells,
      downregulated pro-inflammatory cytokine levels and translocation of NF-kappaB,
      and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified
      inflammation and played an important role in the process of post-OALT related
      ALI.

PMID- 24116035
TI  - Occurrence, formation and function of organic sheets in the mineral tube
      structures of Serpulidae (polychaeta, Annelida).
AB  - A scanning electron microscopy study of organic sheets in serpulid tube mineral
      structures was carried out to discern their function, formation and evolution.
      The organic sheets may have some taxonomic value in distinguishing the two major
      clades of serpulids previously identified. The organic sheets in the mineral tube
      structure occur only in certain taxa belonging to clade A, but not all species in
      clade A have them. Organic sheets are best developed in genus Spirobranchus. One
      could speculate that organic sheets have evolved as an adaption to further
      strengthen the mechanical properties of the tubes in clade A, which contains
      serpulids with the most advanced mineral tube microstructures. The organic sheets
      are presumably secreted with at least some mineral phase. 

PMID- 24116034
TI  - Divergent paths for adult mortality in Russia and Central Asia: evidence from
      Kyrgyzstan.
AB  - Adult mortality has been lower in Kyrgyzstan vs. Russia among males since at
      least 1981 and among females since 1999. Also, Kyrgyzstan's mortality
      fluctuations have had smaller amplitude. This has occurred in spite of worse
      macro-economic outcomes in Kyrgyzstan. To understand these surprising patterns,
      we analyzed cause-specific mortality in Kyrgyzstan vs. Russia for the period 1981
      2010, using unpublished official data. We find that, as in Russia, fluctuations
      in Kyrgyzstan have been primarily due to changes in external causes and
      circulatory causes, and alcohol appears to play an important role. However, in
      contrast with Russia, mortality from these causes in Kyrgyzstan has been lower
      and has increased by a smaller amount. As a result, the mortality gap between the
      two countries is overwhelmingly attributable to external and cardio-vascular
      causes, and more generally, to causes that have been shown to be strongly related
      to alcohol consumption. These cause-specific results, together with the existence
      of large ethnic differentials in mortality in Kyrgyzstan, highlight the
      importance of cultural and religious differences, and their impact on patterns of
      alcohol consumption, in explaining the mortality gap between the two countries.
      These findings show that explanatory frameworks relying solely on macro-economic
      factors are not sufficient for understanding differences in mortality levels and
      trends among former Soviet republics. 

PMID- 24116036
TI  - Novel inhibitor cystine knot peptides from Momordica charantia.
AB  - Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors
      (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine
      Momordica charantia. The sequences of the peptides were determined using mass
      spectrometry and NMR spectroscopy. Using a strategy involving partial reduction
      and stepwise alkylation of the peptides, followed by enzymatic digestion and
      tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was
      elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional
      structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to
      contain the inhibitor cystine knot (ICK) motif. The sequences of the novel
      peptides differ significantly from peptides previously isolated from this plant.
      Therefore, this study expands the known peptide diversity in M. charantia and the
      range of sequences that can be accommodated by the ICK motif. Furthermore, we
      show that a stable two-disulfide intermediate is involved in the oxidative
      folding of MCh-1. This disulfide intermediate is structurally homologous to the
      proposed ancestral fold of ICK peptides, and provides a possible pathway for the
      evolution of this structural motif, which is highly prevalent in nature. 

PMID- 24116037
TI  - Gene expression profiles in human and mouse primary cells provide new insights
      into the differential actions of vitamin D3 metabolites.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) had earlier been regarded as the
      only active hormone. The newly identified actions of 25-hydroxyvitamin D3
      (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin
      D3 endocrine system, however, the current data are fragmented and a systematic
      understanding is lacking. Here we performed the first systematic study of global
      gene expression to clarify their similarities and differences. Three metabolites
      at physiologically comparable levels were utilized to treat human and mouse
      fibroblasts prior to DNA microarray analyses. Human primary prostate stromal
      P29SN cells (hP29SN), which convert 25(OH)D3 into 1alpha,25(OH)2D3 by 1alpha
      hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and
      175 genes by treatment with 1alpha,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3,
      respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1 (-/-)), which
      lack 1alpha-hydroxylation, displayed regulation of 619, 469, and 66 genes using
      the same respective treatments. The number of shared genes regulated by two
      metabolites is much lower in hP29SN than in mCyp27b1 (-/-). By using DAVID
      Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity
      Pathways Analysis, we identified the agonistic regulation of calcium homeostasis
      and bone remodeling between 1alpha,25(OH)2D3 and 25(OH)D3 and unique non
      classical actions of each metabolite in physiological and pathological processes,
      including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis
      signaling, gene transcription, immunomodulation, epigenetics, cell
      differentiation, and membrane protein expression. In conclusion, there are three
      distinct vitamin D3 hormones with clearly different biological activities. This
      study presents a new conceptual insight into the vitamin D3 endocrine system,
      which may guide the strategic use of vitamin D3 in disease prevention and
      treatment. 

PMID- 24116038
TI  - OptZyme: computational enzyme redesign using transition state analogues.
AB  - OptZyme is a new computational procedure for designing improved enzymatic
      activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to
      use transition state analogue compounds, which are known for many reactions, as
      proxies for the typically unknown transition state structures. Mutations that
      minimize the interaction energy of the enzyme with its transition state analogue,
      rather than with its substrate, are identified that lower the transition state
      formation energy barrier. Using Escherichia coli beta-glucuronidase as a
      benchmark system, we confirm that KM correlates (R(2) = 0.960) with the computed
      interaction energy between the enzyme and the para-nitrophenyl- beta, D
      glucuronide substrate, kcat/KM correlates (R(2) = 0.864) with the interaction
      energy of the transition state analogue, 1,5-glucarolactone, and kcat correlates
      (R(2) = 0.854) with a weighted combination of interaction energies with the
      substrate and transition state analogue. OptZyme is subsequently used to identify
      mutants with improved KM, kcat, and kcat/KM for a new substrate, para-nitrophenyl
      beta, D-galactoside. Differences between the three libraries reveal structural
      differences that underpin improving KM, kcat, or kcat/KM. Mutants predicted to
      enhance the activity for para-nitrophenyl- beta, D-galactoside directly or
      indirectly create hydrogen bonds with the altered sugar ring conformation or its
      substituents, namely H162S, L361G, W549R, and N550S. 

PMID- 24116039
TI  - Single-cell analysis reveals early manifestation of cancerous phenotype in pre
      malignant esophageal cells.
AB  - Cellular heterogeneity plays a pivotal role in a variety of functional processes
      in vivo including carcinogenesis. However, our knowledge about cell-to-cell
      diversity and how differences in individual cells manifest in alterations at the
      population level remains very limited mainly due to the lack of appropriate tools
      enabling studies at the single-cell level. We present a study on changes in
      cellular heterogeneity in the context of pre-malignant progression in response to
      hypoxic stress. Utilizing pre-malignant progression of Barrett's esophagus (BE)
      as a disease model system we studied molecular mechanisms underlying the
      progression from metaplastic to dysplastic (pre-cancerous) stage. We used newly
      developed methods enabling measurements of cell-to-cell differences in copy
      numbers of mitochondrial DNA, expression levels of a set of mitochondrial and
      nuclear genes involved in hypoxia response pathways, and mitochondrial membrane
      potential. In contrast to bulk cell studies reported earlier, our study shows
      significant differences between metaplastic and dysplastic BE cells in both
      average values and single-cell parameter distributions of mtDNA copy numbers,
      mitochondrial function, and mRNA expression levels of studied genes. Based on
      single-cell data analysis, we propose that mitochondria may be one of the key
      factors in pre-malignant progression in BE. 

PMID- 24116040
TI  - Association between Mannose-binding lectin gene polymorphisms and hepatitis B
      virus infection: a meta-analysis.
AB  - OBJECTIVE: The results of studies on the relation between Mannose-binding lectin
      gene (mbl2) polymorphism and HBV infection were contradictory and inconclusive.
      In order to shed a light on these inconsistent findings and to clarify the role
      of mbl2 polymorphisms in susceptibility or progression of chronic hepatitis B
      (CHB), a meta-analysis was performed. METHODS: PubMed and Embase were searched
      for available articles. A meta-analysis was performed to examine the association
      between mbl2 polymorphisms and chronicity or progression of hepatitis B
      infection. Odds ratio (OR) and its 95% confidence interval (CI) served as
      indexes. RESULTS: A total of 17 eligible studies were involved, including 2151
      healthy controls (HC), 1293 spontaneous recovered (SR) patients with acute
      infection, 2337 cases with chronic hepatitis B (CHB) and 554 cases with
      progressive hepatitis B. There was no evidence of significant association between
      mbl2 exon1 polymorphisms and CHB risk in any genetic model or pairwise
      comparisons when compared with HC group or SR group. In the stratified analysis
      of ethnic groups, also no obvious relation between mbl2 polymorphism and CHB risk
      was identified. There was still no significant association between the complete
      mbl2 genotypic profile (including both the exon1 and the promoter gene)
      polymorphisms and CHB risk, as compared with SR group. However, it was found that
      there was an association between the mbl2 AO/OO genotype and severe hepatitis B
      (SHB) or liver cirrhosis (LC) (LC vs. HC:OR=3.66, 95%CI, 2.38-5.63; SHB vs. HC,
      OR=3.88, 95%CI, 2.26-6.64), but there was no relationship between the mbl2 AO/OO
      genotype and hepatocellular carcinoma (HCC) (OR=1.26, 95%CI, 0.82-1.94).
      CONCLUSION: The present meta-analysis indicated that mbl2 exon1 polymorphisms
      might not significantly associate with chronicity of HBV infection, but might be
      significantly related to the progressive HBV such as SHB and LC.

PMID- 24116041
TI  - Associations of trunk fat depots with insulin resistance, beta cell function and
      glycaemia--a multiple technique study.
AB  - OBJECTIVE: Central (truncal) adiposity is associated strongly with insulin
      resistance and diabetes. There are very few reports comparing methods of trunk
      fat measurement in their ability to predict glycaemia and insulin resistance. We
      report a comparative analysis of different trunk fat measurements in predicting
      glycaemia and insulin resistance in middle aged Indian men. MATERIALS AND
      METHODS: Trunk fat measurements were performed using anthropometry, magnetic
      resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and computed
      tomography (CT) on 128 men. Additional measurements were taken to characterise
      insulin resistance (Matsuda index) and beta cell function (Insulinogenic Index),
      glycaemia (fasting and 120 min glucose concentrations). Using residual approach
      we compared the ability of different trunk fat measurement techniques to predict
      insulin resistance, beta cell function and glycaemia. RESULTS: There was a strong
      association between trunk fat measures from each technique with glycaemia and
      insulin resistance indices but not with the Insulinogenic Index. Insulin
      resistance and glycaemia, were best predicted using anthropometric measurements,
      notably by waist circumference and subscapular skinfold thickness. Neither MRI
      measures of trunk or visceral fat nor DXA trunk fat added significantly. CT liver
      density contributed to some extent to predict insulin resistance and 120 min
      glucose after anthropometric measurements. CONCLUSIONS: Our results suggest that,
      in Indian men, anthropometric measurements are good predictors of glycaemia and
      insulin resistance. Other complex measurements such as MRI, DXA and CT make only
      a small addition to the prediction. This finding supports the application of
      anthropometry for determining trunk fat in clinical and epidemiological settings.

PMID- 24116042
TI  - Coval: improving alignment quality and variant calling accuracy for next
      generation sequencing data.
AB  - Accurate identification of DNA polymorphisms using next-generation sequencing
      technology is challenging because of a high rate of sequencing error and
      incorrect mapping of reads to reference genomes. Currently available short read
      aligners and DNA variant callers suffer from these problems. We developed the
      Coval software to improve the quality of short read alignments. Coval is designed
      to minimize the incidence of spurious alignment of short reads, by filtering
      mismatched reads that remained in alignments after local realignment and error
      correction of mismatched reads. The error correction is executed based on the
      base quality and allele frequency at the non-reference positions for an
      individual or pooled sample. We demonstrated the utility of Coval by applying it
      to simulated genomes and experimentally obtained short-read data of rice,
      nematode, and mouse. Moreover, we found an unexpectedly large number of
      incorrectly mapped reads in 'targeted' alignments, where the whole genome
      sequencing reads had been aligned to a local genomic segment, and showed that
      Coval effectively eliminated such spurious alignments. We conclude that Coval
      significantly improves the quality of short-read sequence alignments, thereby
      increasing the calling accuracy of currently available tools for SNP and indel
      identification. Coval is available at http://sourceforge.net/projects/coval105/. 

PMID- 24116043
TI  - Kinase activity of ArcB from Escherichia coli is subject to regulation by both
      ubiquinone and demethylmenaquinone.
AB  - Expression of the catabolic network in Escherichia coli is predominantly
      regulated, via oxygen availability, by the two-component system ArcBA. It has
      been shown that the kinase activity of ArcB is controlled by the redox state of
      two critical pairs of cysteines in dimers of the ArcB sensory kinase. Among the
      cellular components that control the redox state of these cysteines of ArcB are
      the quinones from the cytoplasmic membrane of the cell, which function in
      'respiratory' electron transfer. This study is an effort to understand how the
      redox state of the quinone pool(s) is sensed by the cell via the ArcB kinase. We
      report the relationship between growth, quinone content, ubiquinone redox state,
      the level of ArcA phosphorylation, and the level of ArcA-dependent gene
      expression, in a number of mutants of E. coli with specific alterations in their
      set of quinones, under a range of physiological conditions. Our results provide
      experimental evidence for a previously formulated hypothesis that not only
      ubiquinone, but also demethylmenaquinone, can inactivate kinase activity of ArcB.
      Also, in a mutant strain that only contains demethylmenaquinone, the extent of
      ArcA phosphorylation can be modulated by the oxygen supply rate, which shows that
      demethylmenaquinone can also inactivate ArcB in its oxidized form. Furthermore,
      in batch cultures of a strain that contains ubiquinone as its only quinone
      species, we observed that the ArcA phosphorylation level closely followed the
      redox state of the ubiquinone/ubiquinol pool, much more strictly than it does in
      the wild type strain. Therefore, at low rates of oxygen supply in the wild type
      strain, the activity of ArcB may be inhibited by demethylmenaquinone, in spite of
      the fact that the ubiquinones are present in the ubiquinol form. 

PMID- 24116044
TI  - Differential gene expression for Curvularia eragrostidis pathogenic incidence in
      crabgrass (Digitaria sanguinalis) revealed by cDNA-AFLP analysis.
AB  - Gene expression profiles of Digitaria sanguinalis infected by Curvularia
      eragrostidis strain QZ-2000 at two concentrations of conidia and two dew
      durations were analyzed by cDNA amplified fragment length polymorphisms (cDNA
      AFLP). Inoculum strength was more determinant of gene expression than dew
      duration. A total of 256 primer combinations were used for selective
      amplification and 1214 transcript-derived fragments (TDFs) were selected for
      their differential expression. Of these, 518 up-regulated differentially
      expressed TDFs were identified. Forty-six differential cDNA fragments were chosen
      to be cloned and 35 of them were successfully cloned and sequenced, of which 25
      were homologous to genes of known function according to the GenBank database.
      Only 6 genes were up-regulated in Curvularia eragrostidis-inoculated D.
      sanguinalis, with functions involved in signal transduction, energy metabolism,
      cell growth and development, stress responses, abscisic acid biosynthesis and
      response. It appears that a few pathways may be important parts of the pathogenic
      strategy of C. eragrostidis strain QZ-2000 on D. sanguinalis. Our study provides
      the fundamentals to further study the pathogenic mechanism, screen for optimal C.
      eragrostidis strains as potential mycoherbicide and apply this product to control
      D. sanguinalis. 

PMID- 24116045
TI  - Ecological network indicators of ecosystem status and change in the Baltic Sea.
AB  - Several marine ecosystems under anthropogenic pressure have experienced shifts
      from one ecological state to another. In the central Baltic Sea, the regime shift
      of the 1980s has been associated with food-web reorganization and redirection of
      energy flow pathways. These long-term dynamics from 1974 to 2006 have been
      simulated here using a food-web model forced by climate and fishing. Ecological
      network analysis was performed to calculate indices of ecosystem change. The
      model replicated the regime shift. The analyses of indicators suggested that the
      system's resilience was higher prior to 1988 and lower thereafter. The ecosystem
      topology also changed from a web-like structure to a linearized food-web. 

PMID- 24116046
TI  - Emotion-related visual mismatch responses in schizophrenia: impairments and
      correlations with emotion recognition.
AB  - BACKGROUND AND OBJECTIVES: Mismatch negativity (MMN) is an event-related
      potential (ERP) measure of preattentional sensory processing. While deficits in
      the auditory MMN are robust electrophysiological findings in schizophrenia,
      little is known about visual mismatch response and its association with social
      cognitive functions such as emotion recognition in schizophrenia. Our aim was to
      study the potential deficit in the visual mismatch response to unexpected facial
      emotions in schizophrenia and its association with emotion recognition
      impairments, and to localize the sources of the mismatch signals. EXPERIMENTAL
      DESIGN: The sample comprised 24 patients with schizophrenia and 24 healthy
      control subjects. Controls were matched individually to patients by gender, age,
      and education. ERPs were recorded using a high-density 128-channel BioSemi
      amplifier. Mismatch responses to happy and fearful faces were determined in 2
      time windows over six regions of interest (ROIs). Emotion recognition performance
      and its association with the mismatch response were also investigated. PRINCIPAL
      OBSERVATIONS: Mismatch signals to both emotional conditions were significantly
      attenuated in patients compared to controls in central and temporal ROIs.
      Controls recognized emotions significantly better than patients. The association
      between overall emotion recognition performance and mismatch response to the
      happy condition was significant in the 250-360 ms time window in the central ROI.
      The estimated sources of the mismatch responses for both emotional conditions
      were localized in frontal regions, where patients showed significantly lower
      activity. CONCLUSIONS: Impaired generation of mismatch signals indicate
      insufficient automatic processing of emotions in patients with schizophrenia,
      which correlates strongly with decreased emotion recognition.

PMID- 24116047
TI  - Aldehyde dehydrogenase 1 identifies cells with cancer stem cell-like properties
      in a human renal cell carcinoma cell line.
AB  - Cancer stem cells (CSC) or cancer stem cell-like cells (CSC-LCs) have been
      identified in many malignant tumors. CSCs are proposed to be related with drug
      resistance, tumor recurrence, and metastasis and are considered as a new target
      for cancer treatment; however, there are only a few reports on CSCs or CSC-LCs in
      renal cell carcinoma (RCC). Different approaches have been reported for CSC
      identification, but there are no universal markers for CSC. We used two different
      approaches, the traditional side population (SP) approach, and the enzymatic
      (aldehyde dehydrogenase 1 (ALDH1)) approach to identify CSC-LC population in two
      RCC cell lines, ACHN and KRC/Y. We found that ACHN and KRC/Y contain 1.4% and
      1.7% SP cells, respectively. ACHN SP cells showed a higher sphere forming
      ability, drug resistance, and a slightly higher tumorigenic ability in NOD/SCID
      mice than Non-SP (NSP) cells, suggesting that cells with CSC-LC properties are
      included in ACHN SP cells. KRC/Y SP and NSP cells showed no difference in such
      properties. ALDH1 activity analysis revealed that ACHN SP cells expressed a
      higher level of activity than NSP cells (SP vs. NSP: 32.7% vs 14.6%). Analysis of
      ALDH1-positive ACHN cells revealed that they have a higher sphere forming
      ability, self-renewal ability, tumorigenicity and express higher mRNA levels of
      CSC-LC property-related genes (e.g., ABC transporter genes, self-replication
      genes, anti-apoptosis genes, and so forth) than ALDH1-negative cells. Drug
      treatment or exposure to hypoxic condition induced a 2- to 3-fold increase in
      number of ALDH1-positive cells. In conclusion, the results suggest that the ALDH1
      positive cell population rather than SP cells show CSC-LC properties in a RCC
      cell line, ACHN. 

PMID- 24116049
TI  - The importance of pollinator generalization and abundance for the reproductive
      success of a generalist plant.
AB  - Previous studies have examined separately how pollinator generalization and
      abundance influence plant reproductive success, but none so far has evaluated
      simultaneously the relative importance of these pollinator attributes. Here we
      evaluated the extent to which pollinator generalization and abundance influence
      plant reproductive success per visit and at the population level on a generalist
      plant, Opuntia sulphurea (Cactaceae). We used field experiments and path analysis
      to evaluate whether the per-visit effect is determined by the pollinator's degree
      of generalization, and whether the population level effect (pollinator impact) is
      determined by the pollinator's degree of generalization and abundance. Based on
      the models we tested, we concluded that the per-visit effect of a pollinator on
      plant reproduction was not determined by the pollinators' degree of
      generalization, while the population-level impact of a pollinator on plant
      reproduction was mainly determined by the pollinators' degree of generalization.
      Thus, generalist pollinators have the greatest species impact on pollination and
      reproductive success of O. sulphurea. According to our analysis this greatest
      impact of generalist pollinators may be partly explained by pollinator abundance.
      However, as abundance does not suffice as an explanation of pollinator impact, we
      suggest that vagility, need for resource consumption, and energetic efficiency of
      generalist pollinators may also contribute to determine a pollinator's impact on
      plant reproduction. 

PMID- 24116048
TI  - Molecular epidemiology of Clostridium difficile at a medical center in Taiwan:
      persistence of genetically clustering of A-B+ isolates and increase of A+B+
      isolates.
AB  - INTRODUCTION: We investigated the changing trend of various toxigenic Clostridium
      difficile isolates at a 3 500-bed hospital in Taiwan. Genetic relatedness and
      antimicrobial susceptibility of toxigenic C. difficile isolates were also
      examined. METHODS: A total of 110 non-repeat toxigenic C. difficile isolates from
      different patients were collected between 2002 and 2007. Characterization of the
      110 toxigenic isolates was performed using agar dilution method, multilocus
      variable-number tandem-repeat analysis (MLVA) genotyping, tcdC genotyping, and
      toxinotyping. RESULTS: Among the 110 toxigenic isolates studied, 70 isolates
      harbored tcdA and tcdB (A+B+) and 40 isolates harbored tcdB only (A-B+). The
      annual number of A+B+ isolates considerably increased over the 6-year study (P =
      0.055). A total of 109 different MLVA genotypes were identified, in which A+B+
      isolates and A-B+ isolates were differentiated into two genetic clusters with
      similarity of 17.6%. Twenty-four (60%) of the 40 A-B+ isolates formed a major
      cluster, MLVA-group 1, with a similarity of 85%. Seven (6.4%) resistant isolates
      were identified, including two metronidazole-resistant and five vancomycin
      resistant isolates. CONCLUSIONS: This study indicated a persistence of a MLVA
      group 1 A-B+ isolates and an increase of A+B+ isolates with diverse MLVA types.
      Moreover, C. difficile isolates with antimicrobial resistance to metronidazole or
      vancomycin were found to have emerged. Continuous surveillance is warranted to
      understand the recent situation and control the further spread of the toxigenic
      C. difficile isolates, especially among hospitalized patients.

PMID- 24116050
TI  - A single nucleotide polymorphism associated with hepatitis C virus infections
      located in the distal region of the IL28B promoter influences NF-kappaB-mediated
      gene transcription.
AB  - Persistence of hepatitis C virus (HCV) infection is observed only in a subset of
      infected individuals and among them only some respond to treatment. Genome-wide
      association studies (GWAS) carried out around the world identified single
      nucleotide polymorphisms (SNPs) in the IL28B locus that are strongly associated
      with both HCV clearance and treatment response. The functional significance of
      these associations however, is not clear. In this report we show that an SNP
      rs28416813 in the distal promoter region of IL28B that is in close proximity to a
      non-consensus NF-kappaB-binding site affects downstream reporter gene expression.
      The effect is likely due to differential binding of NF-kappaB at the non
      consensus site. The non-protective allele showed a reduction in luciferase
      reporter gene expression compared to the protective allele in HEK293T cells under
      different experimental conditions including treatment with tumor necrosis factor
      alpha (TNF-alpha) and 5' triphosphorylated dsRNA. Furthermore, the HCV RNA
      polymerase was able to induce transcription from the IL28B promoter in a RIG-I
      dependent manner. This induction was influenced by the alleles present at
      rs28416813. We also demonstrate strong linkage disequilibrium between rs28416813
      and another important SNP rs12979860 in two ethnic populations. These results
      suggest possible mechanisms by which SNPs at the IL28B locus influence
      spontaneous clearance and treatment response in chronic HCV infections. 

PMID- 24116051
TI  - MusaWRKY71 overexpression in banana plants leads to altered abiotic and biotic
      stress responses.
AB  - WRKY transcription factors are specifically involved in the transcriptional
      reprogramming following incidence of abiotic or biotic stress on plants. We have
      previously documented a novel WRKY gene from banana, MusaWRKY71, which was
      inducible in response to a wide array of abiotic or biotic stress stimuli. The
      present work details the effects of MusaWRKY71 overexpression in transgenic
      banana plants. Stable integration and overexpression of MusaWRKY71 in transgenic
      banana plants was proved by Southern blot analysis and quantitative real time
      PCR. Transgenic banana plants overexpressing MusaWRKY71 displayed enhanced
      tolerance towards oxidative and salt stress as indicated by better photosynthesis
      efficiency (Fv/Fm) and lower membrane damage of the assayed leaves. Further,
      differential regulation of putative downstream genes of MusaWRKY71 was
      investigated using real-time RT-PCR expression analysis. Out of a total of 122
      genes belonging to WRKY, pathogenesis-related (PR) protein genes, non-expressor
      of pathogenesis-related genes 1 (NPR1) and chitinase families analyzed, 10 genes
      (six belonging to WRKY family, three belonging to PR proteins family and one
      belonging to chitinase family) showed significant differential regulation in
      MusaWRKY71 overexpressing lines. These results indicate that MusaWRKY71 is an
      important constituent in the transcriptional reprogramming involved in diverse
      stress responses in banana. 

PMID- 24116052
TI  - Fetal adrenal gland in the second half of gestation: morphometrical assessment
      with 3.0T post-mortem MRI.
AB  - BACKGROUND: The morphometry of fetal adrenal gland is rarely described with MRI
      of high magnetic field. The purpose of this study is to assess the normal fetal
      adrenal gland length (AL), width (AW), height (AH), surface area (AS) and volume
      (AV) in the second half of gestation with 3.0T post-mortem MRI. METHODS AND
      FINDINGS: Fifty-two fetal specimens of 23-40 weeks gestational age (GA) were
      scanned by 3.0T MRI. Morphological changes and quantitative measurements of the
      fetal adrenal gland were analyzed. Asymmetry and sexual dimorphism were also
      obtained. The shape of the fetal adrenal gland did not change substantially from
      23 to 40 weeks GA. The bilateral adrenal glands appeared as a 'Y', pyramidal or
      half-moon shape after reconstruction. There was a highly linear correlation
      between AL, AW, AH, AS, AV and GA. AW, AH, AS and AV were larger for the left
      adrenal gland than the right. No sexual dimorphism was found. CONCLUSIONS: Our
      data delineated the normal fetal adrenal gland during the second half of
      gestation, and can serve as a useful precise reference for anatomy or in vivo
      fetus.

PMID- 24116053
TI  - Olomoucine II, but not purvalanol A, is transported by breast cancer resistance
      protein (ABCG2) and P-glycoprotein (ABCB1).
AB  - Purine cyclin-dependent kinase inhibitors have been recognized as promising
      candidates for the treatment of various cancers; nevertheless, data regarding
      interaction of these substances with drug efflux transporters is still lacking.
      Recently, we have demonstrated inhibition of breast cancer resistance protein
      (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able
      to synergistically potentiate the antiproliferative effect of mitoxantrone, an
      ABCG2 substrate. In this follow up study, we investigated whether olomoucine II
      and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using
      monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we
      demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of
      both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine
      II will be affected by both ABCB1 and ABCG2 transport proteins, which might
      potentially result in limited accumulation of the compound in tumor tissues or
      lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the
      other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically
      favoring this drug in the potential treatment of efflux transporter-based
      multidrug resistant tumors. In addition, we observed intensive sulfatation of
      olomoucine II in MDCKII cell lines with subsequent active efflux of the
      metabolite out of the cells. Therefore, care should be taken when performing
      pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates
      are used; the generated sulfated conjugate may largely contaminate
      pharmacokinetic analysis and result in misleading interpretation. With regard to
      chemical structures of olomoucine II and purvalanol A, our data emphasize that
      even drugs with remarkable structure similarity may show different
      pharmacokinetic behavior such as interactions with ABC transporters or
      biotransformation enzymes. 

PMID- 24116054
TI  - Adiponectin provides additional information to conventional cardiovascular risk
      factors for assessing the risk of atherosclerosis in both genders.
AB  - BACKGROUND: This study evaluated the relation between adiponectin and
      atherosclerosis in both genders, and investigated whether adiponectin provides
      useful additional information for assessing the risk of atherosclerosis. METHODS:
      We measured serum adiponectin levels and other cardiovascular risk factors in
      1033 subjects (454 men, 579 women) from the Korean Genomic Rural Cohort study.
      Carotid intima-media-thickness (CIMT) was used as measure of atherosclerosis.
      Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using
      multiple logistic regression, and receiver operating characteristic curves (ROC),
      the category-free net reclassification improvement (NRI) and integrated
      discrimination improvement (IDI) were calculated. RESULTS: After adjustment for
      conventional cardiovascular risk factors, such as age, waist circumference,
      smoking history, low-density and high-density lipoprotein cholesterol,
      triglycerides, systolic blood pressure and insulin resistance, the ORs (95%CI) of
      the third tertile adiponectin group were 0.42 (0.25-0.72) in men and 0.47 (0.29
      0.75) in women. The area under the curve (AUC) on the ROC analysis increased
      significantly by 0.025 in men and 0.022 in women when adiponectin was added to
      the logistic model of conventional cardiovascular risk factors (AUC in men: 0.655
      to 0.680, p = 0.038; AUC in women: 0.654 to 0.676, p = 0.041). The NRI was 0.32
      (95%CI: 0.13-0.50, p<0.001), and the IDI was 0.03 (95%CI: 0.01-0.04, p<0.001) for
      men. For women, the category-free NRI was 0.18 (95%CI: 0.02-0.34, p = 0.031) and
      the IDI was 0.003 (95%CI: -0.002-0.008, p = 0.189). CONCLUSION: Adiponectin and
      atherosclerosis were significantly related in both genders, and these
      relationships were independent of conventional cardiovascular risk factors.
      Furthermore, adiponectin provided additional information to conventional
      cardiovascular risk factors regarding the risk of atherosclerosis.

PMID- 24116055
TI  - Growth but not photosynthesis response of a host plant to infection by a
      holoparasitic plant depends on nitrogen supply.
AB  - Parasitic plants can adversely influence the growth of their hosts by removing
      resources and by affecting photosynthesis. Such negative effects depend on
      resource availability. However, at varied resource levels, to what extent the
      negative effects on growth are attributed to the effects on photosynthesis has
      not been well elucidated. Here, we examined the influence of nitrogen supply on
      the growth and photosynthesis responses of the host plant Mikania micrantha to
      infection by the holoparasite Cuscuta campestris by focusing on the interaction
      of nitrogen and infection. Mikania micrantha plants fertilized at 0.2, 1 and 5 mM
      nitrate were grown with and without C. campestris infection. We observed that the
      infection significantly reduced M. micrantha growth at each nitrate fertilization
      and more severely at low than at high nitrate. Such alleviation at high nitrate
      was largely attributed to a stronger influence of infection on root biomass at
      low than at high nitrate fertilization. However, although C. campestris altered
      allometry and inhibited host photosynthesis, the magnitude of the effects was
      independent of nitrate fertilizations. The infection reduced light saturation
      point, net photosynthesis at saturating irradiances, apparent quantum yield, CO2
      saturated rate of photosynthesis, carboxylation efficiency, the maximum
      carboxylation rate of Rubisco, and maximum light-saturated rate of electron
      transport, and increased light compensation point in host leaves similarly across
      nitrate levels, corresponding to a similar magnitude of negative effects of the
      parasite on host leaf soluble protein and Rubisco concentrations, photosynthetic
      nitrogen use efficiency and stomatal conductance across nitrate concentrations.
      Thus, the more severe inhibition in host growth at low than at high nitrate
      supplies cannot be attributed to a greater parasite-induced reduction in host
      photosynthesis, but the result of a higher proportion of host resources
      transferred to the parasite at low than at high nitrate levels. 

PMID- 24116056
TI  - The effects of hematopoietic growth factors on neurite outgrowth.
AB  - Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are
      initially discovered as the essential hematopoietic growth factors regulating
      bone marrow stem cell proliferation and differentiation, and SCF in combination
      with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell
      mobilization. In this study we have determined the effect of SCF and G-CSF on
      neurite outgrowth in rat cortical neurons. Using molecular and cellular biology
      and live cell imaging approaches, we have revealed that receptors for SCF and G
      CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF
      synergistically enhances neurite extension through PI3K/AKT and NFkappaB
      signaling pathways. Moreover, SCF+G-CSF induces much greater NFkappaB activation,
      NFkappaB transcriptional binding and brain-derived neurotrophic factor (BDNF)
      production than SCF or G-CSF alone. In addition, we have also observed that BDNF,
      the target gene of NFkappaB, is required for SCF+G-CSF-induced neurite outgrowth.
      These data suggest that SCF+G-CSF has synergistic effects to promote neurite
      growth. This study provides new insights into the contribution of hematopoietic
      growth factors in neuronal plasticity. 

PMID- 24116057
TI  - Comparative population dynamics of two closely related species differing in
      ploidy level.
AB  - BACKGROUND: Many studies compare the population dynamics of single species within
      multiple habitat types, while much less is known about the differences in
      population dynamics in closely related species in the same habitat. Additionally,
      comparisons of the effect of habitat types and species are largely missing.
      METHODOLOGY AND PRINCIPAL FINDINGS: We estimated the importance of the habitat
      type and species for population dynamics of plants. Specifically, we compared the
      dynamics of two closely related species, the allotetraploid species Anthericum
      liliago and the diploid species Anthericum ramosum, occurring in the same habitat
      type. We also compared the dynamics of A. ramosum in two contrasting habitats. We
      examined three populations per species and habitat type. The results showed that
      single life history traits as well as the mean population dynamics of A. liliago
      and A. ramosum from the same habitat type were more similar than the population
      dynamics of A. ramosum from the two contrasting habitats. CONCLUSIONS: Our
      findings suggest that when transferring knowledge regarding population dynamics
      between populations, we need to take habitat conditions into account, as these
      conditions appear to be more important than the species involved (ploidy level).
      However, the two species differ significantly in their overall population growth
      rates, indicating that the ploidy level has an effect on species performance. In
      contrast to what has been suggested by previous studies, we observed a higher
      population growth rate in the diploid species. This is in agreement with the
      wider range of habitats occupied by the diploid species.

PMID- 24116058
TI  - Prevalence of cataract surgery and visual outcomes in Indian immigrants in
      Singapore: the Singapore Indian eye study.
AB  - OBJECTIVE: To determine the prevalence of cataract surgery and factors associated
      with post-surgical visual outcomes in migrant Indians living in Singapore.
      RESEARCH DESIGN AND METHODS: We conducted a population-based study in 3,400
      Indian immigrants residing in Singapore-the Singapore Indian Eye Study (SINDI).
      All participants underwent comprehensive medical eye examination and a
      standardized interview. Post-operative visual impairment (VI) was defined as best
      corrected or presenting visual acuity (BCVA or PVA) of 20/60 or worse. RESULTS:
      The age- and gender-standardized prevalence of cataract surgery was 9.7% (95%
      confidence interval [CI]: 8.9%, 10.7%) in Singapore resident Indians. Post
      operative VI defined by BCVA occurred in 10.9% eyes (87/795). The main causes of
      post-operative VI were diabetic retinopathy (20.7%), posterior capsular
      opacification (18.4%), and age-related macular degeneration (12.6%).
      Undercorrected refractive error doubled the prevalence of post-operative VI when
      PVA was used. CONCLUSIONS: The rate of cataract surgery is about 10% in Indian
      residents in Singapore. Socioeconomic variables and migration had no significant
      impact on the prevalence of cataract surgery. Diabetic retinopathy was a major
      cause of post-operative VI in migrant Indians living in Singapore. Uncorrected
      postoperative refractive error remains an efficient way to improve vision.

PMID- 24116059
TI  - The revolving door phenomenon revisited: time to readmission in 17'145
      [corrected] patients with 37'697 hospitalisations at a German psychiatric
      hospital.
AB  - OBJECTIVE: Despite the recurring nature of the disease process in many
      psychiatric patients, individual careers and time to readmission rarely have been
      analysed by statistical models that incorporate sequence and velocity of
      recurrent hospitalisations. This study aims at comparing four statistical models
      specifically designed for recurrent event history analysis and evaluating the
      potential impact of predictor variables from different sources (patient,
      treatment process, social environment). METHOD: The so called Andersen-Gil
      counting process model, two variants of the conditional models of Prentice,
      Williams, and Peterson (gap time model, conditional probability model), and the
      so called frailty model were applied to a dataset of 17'145 [corrected] patients
      observed during a 12 years period starting from 1996 and leading to 37'697
      psychiatric hospitalisations Potential prognostic factors stem from a
      standardized patient documentation form. RESULTS: Estimated regression
      coefficients over different models were highly similar, but the frailty model
      best represented the sequentiality of individual treatment careers and differing
      velocities of disease progression. It also avoided otherwise likely
      misinterpretations of the impact of gender, partnership, historical time and
      length of stay. A widespread notion of psychiatric diseases as inevitably chronic
      and worsening could be rejected. Time in community was found to increase over
      historical time for all patients. Most important protective factors beyond
      diagnosis were employment, partnership, and sheltered living situation. Risky
      conditions were urban living and a concurrent substance use disorder. CONCLUSION:
      Prognostic factors for course of diseases should be determined only by
      statistical models capable of adequately incorporating the recurrent nature of
      psychiatric illnesses.

PMID- 24116060
TI  - Multiple protein domains contribute to nuclear import and cell toxicity of DUX4,
      a candidate pathogenic protein for facioscapulohumeral muscular dystrophy.
AB  - DUX4 (Double Homeobox Protein 4) is a nuclear transcription factor encoded at
      each D4Z4 unit of a tandem-repeat array at human chromosome 4q35. DUX4
      constitutes a major candidate pathogenic protein for facioscapulohumeral muscular
      dystrophy (FSHD), the third most common form of inherited myopathy. A low-level
      expression of DUX4 compromises cell differentiation in myoblasts and its
      overexpression induces apoptosis in cultured cells and living organisms. In this
      work we explore potential molecular determinants of DUX4 mediating nuclear import
      and cell toxicity. Deletion of the hypothetical monopartite nuclear localization
      sequences RRRR(23), RRKR(98) and RRAR(148) (i.e. NLS1, NLS2 and NLS3,
      respectively) only partially delocalizes DUX4 from the cell nuclei. Nuclear
      entrance guided by NLS1, NLS2 and NLS3 does not follow the classical nuclear
      import pathway mediated by alpha/beta importins. NLS and homeodomain mutants from
      DUX4 are dramatically less cell-toxic than the wild type molecule, independently
      of their subcellular localization. A triple DeltaNLS1-2-3 deletion mutant is
      still partially localized in the nuclei, indicating that additional sequences in
      DUX4 contribute to nuclear import. Deletion of >=111 amino acids from the C
      terminal of DUX4, on a DeltaNLS1-2-3 background, almost completely re-localizes
      DUX4 to the cytoplasm, indicating that the C-ter tail contributes to subcellular
      trafficking of DUX4. Also, C-terminal deletion mutants of DUX4 on a NLS wild type
      background are less toxic than wild type DUX4. Results reported here indicate
      that DUX4 possesses redundant mechanisms to assure nuclear entrance and that its
      various transcription-factor associated domains play an essential role in cell
      toxicity. 

PMID- 24116061
TI  - Reliability of visual assessment of non-contrast CT, CT angiography source images
      and CT perfusion in patients with suspected ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Good reliability of methods to assess the extent of
      ischemia in acute stroke is important for implementation in clinical practice,
      especially between observers with varying experience. Our aim was to determine
      inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA)
      rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT
      modalities in patients suspected of acute ischemic stroke. METHODS: We
      prospectively included 105 patients with acute neurological deficit due to
      suspected acute ischemic stroke within 9 hours after symptom onset. All patients
      underwent non-contrast CT, CT perfusion and CT angiography on admission. All
      images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA
      involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra
      observer agreement. We used kappa statistics and intraclass correlation
      coefficient to calculate agreement. RESULTS: Inter-observer agreement for the 1/3
      MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT
      angiography source images, but excellent for all CT perfusion maps (cerebral
      blood volume, mean transit time, and predicted penumbra and infarct maps). Intra
      observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non
      contrast CT, fair to moderate for CT angiography source images, and good to
      excellent for all CT perfusion maps. CONCLUSION: Between observers with a
      different level of experience, agreement on the radiological diagnosis of
      cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT
      angiography source images, and therefore CT perfusion is a very reliable addition
      to standard stroke imaging.

PMID- 24116062
TI  - Applicability of the Chinese version of the Hypomania Symptom Checklist (HCL-32)
      scale for outpatients of psychiatric departments in general hospitals.
AB  - OBJECTIVES: This study aimed to determine the suitability of the Chinese version
      of the Hypomania Symptom Checklist (HCL-32) scale for psychiatric department
      outpatients with mood disorders in Chinese general hospitals, and provide a
      theoretical basis for the application of the HCL-32 scale. METHODS: Outpatients
      with mood disorders receiving continuous treatment in the psychiatric medicine
      department of three top-ranking general hospitals in three cities completed
      scoring the HCL-32 scale. RESULTS: A total of 1010 patients were recruited. 417
      were diagnosed with bipolar disorder (236 for type I and 181 for type II) and 593
      were depression. Four factors with eigenvalues >1 were considered. Factor 1 with
      an eigenvalue of 5.5 was labeled "active/cheerful". Factor 2 with an eigenvalue
      of 2.7 was labeled "adventurous/irritable." The coefficient of internal
      consistency reliability of the HCL-32 total scale was 0.84, and the coefficients
      for factors 1 and 2 were 0.84 and 0.88, respectively. With the total score of HCL
      32>=14 as positive standard, the sensitivity of HCL-32 was calculated at 69.30%
      and the specificity was 97.81%. CONCLUSIONS: Results showed that HCL-32 had a
      preferable reliability and validity and was suitable as auxiliary means for
      bipolar disorder screening in general hospitals.

PMID- 24116063
TI  - Obesity and association with area of residence, gender and socio-economic factors
      in Algerian and Tunisian adults.
AB  - INTRODUCTION: The epidemiological transition has resulted in a major increase in
      the prevalence of obesity in North Africa. This study investigated differences in
      obesity and its association with area of residence, gender and socio-economic
      position among adults in Algeria and Tunisia, two countries with socio-economic
      and socio-cultural similarities. METHODS: Cross-sectional studies used
      stratified, three-level, clustered samples of 35-70 year old adults in Algeria,
      (women n = 2741, men n = 2004) and Tunisia (women n = 2964, men n = 2379).
      Thinness was defined as Body Mass Index (BMI) = weight/height <18.5 kg/m(2),
      obesity as BMI >=30, and abdominal obesity as waist circumference/height >=0.6.
      Associations with area of residence, gender, age, education, profession and
      household welfare were assessed. RESULTS: Prevalence of thinness was very low
      except among men in Algeria (7.3% C.I.[5.9-8.7]). Prevalence of obesity among
      women was high in Algeria (30.1% C.I.[27.8-32.4]) and Tunisia (37.0% C.I.[34.4
      39.6]). It was less so among men (9.1% C.I.[7.1-11.0] and 13.3% C.I.[11.2
      15.4]).The results were similar for abdominal obesity. In both countries women
      were much more obesity-prone than men: the women versus men obesity Odds-Ratio
      was 4.3 C.I.[3.4-5.5] in Algeria and 3.8 C.I.[3.1-4.7] in Tunisia. Obesity was
      more prevalent in urban versus rural areas in Tunisia, but not in Algeria (e.g.
      for women, urban versus rural Odds-Ratio was 2.4 C.I.[1.9-3.1] in Tunisia and
      only 1.2 C.I.[1.0-5.5] in Algeria). Obesity increased with household welfare, but
      more markedly in Tunisia, especially among women. Nevertheless, in both
      countries, even in the lowest quintile of welfare, a fifth of the women were
      obese. CONCLUSION: The prevention of obesity, especially in women, is a public
      health issue in both countries, but there were differences in the patterning of
      obesity according to area of residence and socio-economic position. These
      specificities must be taken into account in the management of obesity
      inequalities.

PMID- 24116064
TI  - Corynebacterium jeikeium jk0268 constitutes for the 40 amino acid long PorACj,
      which forms a homooligomeric and anion-selective cell wall channel.
AB  - Corynebacterium jeikeium, a resident of human skin, is often associated with
      multidrug resistant nosocomial infections in immunodepressed patients. C.
      jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and
      contains a channel-forming protein as judged from reconstitution experiments with
      artificial lipid bilayer experiments. The channel-forming protein was present in
      detergent treated cell walls and in extracts of whole cells using organic
      solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible
      for the pore-forming activity was identified in the known genome of C. jeikeium
      by its similar chromosomal localization to known porH and porA genes of other
      Corynebacterium strains. The gene jk0268 was expressed in a porin deficient
      Corynebacterium glutamicum strain. For purification temporarily histidine-tailed
      or with a GST-tag at the N-terminus, the homogeneous protein caused channel
      forming activity with an average conductance of 1.25 nS in 1M KCl identical to
      the channels formed by the detergent extracts. Zero-current membrane potential
      measurements of the voltage dependent channel implied selectivity for anions.
      This preference is according to single-channel analysis caused by some excess of
      cationic charges located in the channel lumen formed by oligomeric alpha-helical
      wheels. The channel has a suggested diameter of 1.4 nm as judged from the
      permeability of different sized hydrated anions using the Renkin correction
      factor. Surprisingly, the genome of C. jeikeium contained only one gene coding
      for a cell wall channel of the PorA/PorH type found in other Corynebacterium
      species. The possible evolutionary relationship between the heterooligomeric
      channels formed by certain Corynebacterium strains and the homooligomeric pore of
      C. jeikeium is discussed. 

PMID- 24116065
TI  - Differences in cell morphometry, cell wall topography and gp70 expression
      correlate with the virulence of Sporothrix brasiliensis clinical isolates.
AB  - Sporotrichosis is a chronic infectious disease affecting both humans and animals.
      For many years, this subcutaneous mycosis had been attributed to a single
      etiological agent; however, it is now known that this taxon consists of a complex
      of at least four pathogenic species, including Sporothrix schenckii and
      Sporothrix brasiliensis. Gp70 was previously shown to be an important antigen and
      adhesin expressed on the fungal cell surface and may have a key role in
      immunomodulation and host response. The aim of this work was to study the
      virulence, morphometry, cell surface topology and gp70 expression of clinical
      isolates of S. brasiliensis compared with two reference strains of S. schenckii.
      Several clinical isolates related to severe human cases or associated with the
      Brazilian zoonotic outbreak of sporotrichosis were genotyped and clustered as S.
      brasiliensis. Interestingly, in a murine subcutaneous model of sporotrichosis,
      these isolates showed a higher virulence profile compared with S. schenckii. A
      single S. brasiliensis isolate from an HIV-positive patient not only showed lower
      virulence but also presented differences in cell morphometry, cell wall
      topography and abundant gp70 expression compared with the virulent isolates. In
      contrast, the highly virulent S. brasiliensis isolates showed reduced levels of
      cell wall gp70. These observations were confirmed by the topographical location
      of the gp70 antigen using immunoelectromicroscopy in both species. In addition,
      the gp70 molecule was sequenced and identified using mass spectrometry, and the
      sequenced peptides were aligned into predicted proteins using Blastp with the S.
      schenckii and S. brasiliensis genomes. 

PMID- 24116066
TI  - Genetic diversity and population structure of Miscanthus sinensis germplasm in
      China.
AB  - Miscanthus is a perennial rhizomatous C4 grass native to East Asia. Endowed with
      great biomass yield, high ligno-cellulose composition, efficient use of
      radiation, nutrient and water, as well as tolerance to stress, Miscanthus has
      great potential as an excellent bioenergy crop. Despite of the high potential for
      biomass production of the allotriploid hybrid M. *giganteus, derived from M.
      sacchariflorus and M. sinensis, other options need to be explored to improve the
      narrow genetic base of M. *giganteus, and also to exploit other Miscanthus
      species, including M. sinensis (2n = 2x = 38), as bioenergy crops. In the present
      study, a large number of 459 M. sinensis accessions, collected from the wide
      geographical distribution regions in China, were genotyped using 23 SSR markers
      transferable from Brachypodium distachyon. Genetic diversity and population
      structure were assessed. High genetic diversity and differentiation of the
      germplasm were observed, with 115 alleles in total, a polymorphic rate of 0.77,
      Nei's genetic diversity index (He) of 0.32 and polymorphism information content
      (PIC) of 0.26. Clustering of germplasm accessions was primarily in agreement with
      the natural geographic distribution. AMOVA and genetic distance analyses
      confirmed the genetic differentiation in the M. sinensis germplasm and it was
      grouped into five clusters or subpopulations. Significant genetic variation among
      subpopulations indicated obvious genetic differentiation in the collections, but
      within-subpopulation variation (83%) was substantially greater than the between
      subpopulation variation (17%). Considerable phenotypic variation was observed for
      multiple traits among 300 M. sinensis accessions. Nine SSR markers were found to
      be associated with heading date and biomass yield. The diverse Chinese M.
      sinensis germplasm and newly identified SSR markers were proved to be valuable
      for breeding Miscanthus varieties with desired bioenergy traits. 

PMID- 24116067
TI  - Role of cysteines in the stability and DNA-binding activity of the hypochlorite
      specific transcription factor HypT.
AB  - Reactive oxygen species are important components of the immune response.
      Hypochlorite (HOCl) is produced by neutrophils to kill invading microorganisms.
      The bactericidal activity of HOCl is due to proteome-wide unfolding and oxidation
      of proteins at cysteine and methionine residues. Escherichia coli cells are
      protected from HOCl-killing by the previously identified dodecameric
      transcription factor HypT (YjiE). Here, we aimed to unravel whether HOCl
      activates HypT directly or via a reaction product of HOCl with a cellular
      component. Bacterial viability assays and analysis of target gene regulation
      indicate that HypT is highly specific to activation by HOCl and that no reaction
      products of HOCl such as monochloramine, hydroxyl radicals, or methionine
      sulfoxide activate HypT in vivo. Surprisingly, purified HypT lost its DNA-binding
      activity upon incubation with HOCl or reaction products that oxidize HypT to form
      a disulfide-linked dimer, and regained DNA-binding activity upon reduction. Thus,
      we postulate that the cysteines in HypT contribute to control the DNA-binding
      activity of HypT in vitro. HypT contains five cysteine residues; a HypT mutant
      with all cysteines substituted by serine is aggregation-prone and forms tetramers
      in addition to the typical dodecamers. Using single and multiple cysteine-to
      serine mutants, we identified Cys150 to be required for stability and Cys4 being
      important for oligomerization of HypT to dodecamers. Further, oxidation of Cys4
      is responsible for the loss of DNA-binding of HypT upon oxidation in vitro. It
      appears that Cys4 oxidation upon conditions that are insufficient to stimulate
      the DNA-binding activity of HypT prevents unproductive interactions of HypT with
      DNA. Thus, Cys4 oxidation may be a check point in the activation process of HypT.

PMID- 24116068
TI  - Genetic characteristics of the human hepatic stellate cell line LX-2.
AB  - The human hepatic cell line LX-2 has been described as tool to study mechanisms
      of hepatic fibrogenesis and the testing of antifibrotic compounds. It was
      originally generated by immortalisation with the Simian Vacuolating Virus 40
      (SV40) transforming (T) antigen and subsequent propagation in low serum
      conditions. Although this immortalized line is used in an increasing number of
      studies, detailed genetic characterisation has been lacking. We here have
      performed genetic characterisation of the LX-2 cell line and established a single
      locus short tandem repeat (STR) profile for the cell line and characterized the
      LX-2 karyotype by several cytogenetic and molecular cytogenetic techniques.
      Spectral karyotyping (SKY) revealed a complex karyotype with a set of aberrations
      consistently present in the metaphases analyses which might serve as cytogenetic
      markers. In addition, various subclonal and single cell aberrations were
      detected. Our study provides criteria for genetic authentication of LX-2 and
      offers insights into the genotype changes which might underlie part of its
      phenotypic features. 

PMID- 24116069
TI  - Androgen receptor CAG repeats length polymorphism and the risk of polycystic
      ovarian syndrome (PCOS).
AB  - OBJECTIVE: Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen
      excess disorder characterized by multiple small follicles located at the ovarian
      periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen
      receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length
      variations may affect PCOS risk. METHODS: CAG repeat region of 169 patients
      recruited following strictly defined Rotterdam (2003) inclusion criteria and that
      of 175 ethnically similar control samples, were analyzed. We also conducted a
      meta-analysis on the data taken from published studies, to generate a pooled
      estimate on 2194 cases and 2242 controls. RESULTS: CAG bi-allelic mean length was
      between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and
      between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any
      significant difference between the two groups. Further, comparison of bi-allelic
      mean and its frequency distribution in three categories (short, moderate and long
      alleles) did not show any significant difference between controls and various
      case subgroups. Frequency distribution of bi-allelic mean in two categories
      (extreme and moderate alleles) showed over-representation of extreme sized
      alleles in the cases with marginally significant value (50.3% vs. 61.5%, chi(2) =
      4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction
      for multiple comparisons. X-chromosome inactivation analysis showed no
      significant difference in the inactivation pattern of CAG alleles or in the
      comparison of weighed bi-allelic mean between cases and controls. Meta-analysis
      also showed no significant correlation between CAG length and PCOS risk, except a
      minor over-representation of short CAG alleles in the cases. CONCLUSION: CAG bi
      allelic mean length did not differ between controls and cases/case sub-groups nor
      did the allele distribution. Over-representation of short/extreme-sized alleles
      in the cases may be a chance finding without any true association with PCOS risk.

PMID- 24116070
TI  - Alternative mRNA splicing generates two distinct ADAM12 prodomain variants.
AB  - Human ADAM12, transcript variant 1 (later on referred to as Var-1b), present in
      publicly available databases contains the sequence 5'-GTAATTCTG-3' at the
      nucleotide positions 340-348 of the coding region, at the 3' end of exon 4. The
      translation product of this variant, ADAM12-Lb, includes the three amino acid
      motif (114)VIL(116) in the prodomain. This motif is not conserved in ADAM12 from
      different species and is not present in other human ADAMs. Currently, it is not
      clear whether a shorter variant, Var-1a, encoding the protein version without the
      (114)VIL(116) motif, ADAM12-La, is expressed in human. In this work, we have
      established that human mammary epithelial cells and breast cancer cells express
      both Var-1a and Var-1b transcripts. Importantly, the proteolytic processing and
      intracellular trafficking of the corresponding ADAM12-La and ADAM12-Lb proteins
      are different. While ADAM12-La is cleaved and trafficked to the cell surface in a
      manner similar to ADAM12 in other species, ADAM12-Lb is retained in the ER and is
      not proteolytically processed. Furthermore, the relative abundance of ADAM12-La
      and ADAM12-Lb proteins detected in several breast cancer cell lines varies
      significantly. We conclude that the canonical form of transmembrane ADAM12 is
      represented by Var-1a/ADAM12-La, rather than Var-1b/ADAM12-Lb currently featured
      in major sequence databases. 

PMID- 24116071
TI  - Oxidative stress in mammalian cells impinges on the cysteines redox state of
      human XRCC3 protein and on its cellular localization.
AB  - In vertebrates, XRCC3 is one of the five Rad51 paralogs that plays a central role
      in homologous recombination (HR), a key pathway for maintaining genomic
      stability. While investigating the potential role of human XRCC3 (hXRCC3) in the
      inhibition of DNA replication induced by UVA radiation, we discovered that hXRCC3
      cysteine residues are oxidized following photosensitization by UVA. Our in silico
      prediction of the hXRCC3 structure suggests that 6 out of 8 cysteines are
      potentially accessible to the solvent and therefore potentially exposed to ROS
      attack. By non-reducing SDS-PAGE we show that many different oxidants induce
      hXRCC3 oxidation that is monitored in Chinese hamster ovarian (CHO) cells by
      increased electrophoretic mobility of the protein and in human cells by a slight
      decrease of its immunodetection. In both cell types, hXRCC3 oxidation was
      reversed in few minutes by cellular reducing systems. Depletion of intracellular
      glutathione prevents hXRCC3 oxidation only after UVA exposure though depending on
      the type of photosensitizer. In addition, we show that hXRCC3 expressed in CHO
      cells localizes both in the cytoplasm and in the nucleus. Mutating all hXRCC3
      cysteines to serines (XR3/S protein) does not affect the subcellular localization
      of the protein even after exposure to camptothecin (CPT), which typically induces
      DNA damages that require HR to be repaired. However, cells expressing mutated
      XR3/S protein are sensitive to CPT, thus highlighting a defect of the mutant
      protein in HR. In marked contrast to CPT treatment, oxidative stress induces
      relocalization at the chromatin fraction of both wild-type and mutated protein,
      even though survival is not affected. Collectively, our results demonstrate that
      the DNA repair protein hXRCC3 is a target of ROS induced by environmental factors
      and raise the possibility that the redox environment might participate in
      regulating the HR pathway. 

PMID- 24116072
TI  - Sigma-1 receptor enhances neurite elongation of cerebellar granule neurons via
      TrkB signaling.
AB  - Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed
      in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various
      synthetic compounds including well-known psychotherapeutic drugs in the central
      nervous system (CNS). For that, it is considered as an alternative target for
      psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is
      known to play a role in neuroprotection and neurite elongation. These effects are
      suggested to be mediated by its ligand-operated molecular chaperone activity,
      and/or upregulation of various Ca(2+) signaling. In addition, recent studies show
      that Sig-1R activation induces neurite outgrowth via neurotrophin signaling.
      Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation
      through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin
      receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE
      084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and
      K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in
      cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts
      with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706.
      Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in
      CGNs through Y515 phosphorylation of TrkB. 

PMID- 24116073
TI  - Alcohol impairs predation risk response and communication in zebrafish.
AB  - The effects of ethanol exposure on Danio rerio have been studied from the
      perspectives of developmental biology and behavior. However, little is known
      about the effects of ethanol on the prey-predator relationship and chemical
      communication of predation risk. Here, we showed that visual contact with a
      predator triggers stress axis activation in zebrafish. We also observed a typical
      stress response in zebrafish receiving water from these conspecifics, indicating
      that these fish chemically communicate predation risk. Our work is the first to
      demonstrate how alcohol effects this prey-predator interaction. We showed for the
      first time that alcohol exposure completely blocks stress axis activation in both
      fish seeing the predator and in fish that come in indirect contact with a
      predator by receiving water from these conspecifics. Together with other research
      results and with the translational relevance of this fish species, our data
      points to zebrafish as a promising animal model to study human alcoholism. 

PMID- 24116074
TI  - Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type
      cytokine signaling correlates with clinical implications.
AB  - BACKGROUND: The signal transducers and activators of transcription 3 (STAT3)
      signaling pathway plays important roles in oncogenesis, angiogenesis, immunity,
      and tumor cell invasion. In the present study, we investigated the association of
      interleukin (IL)-6/STAT3 signaling pathway with T lymphocytes and clinical
      implication in patients with gastric cancer. METHODS: Seventy one patients who
      underwent gastrectomy due to gastric adenocarcinoma were studied. Blood samples
      were collected before and after surgical gastrectomy to quantify the levels of IL
      6, IL-10 and VEGF using an enzyme-linked immunosorbent assay, as well as T
      lymphocyte subsets (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) and natural killer
      (NK) cells by a flow cytometry. Furthermore, the expression of IL-6, survivin,
      STAT3, STAT3 phosphorylation (p-STAT3), and VEGF were determined in human gastric
      cancer and adjacent normal mucosa through Western blot and immunohistochemistry.
      RESULTS: Postoperative levels of IL-6, IL-10 and VEGF in serum were significantly
      lower than preoperative levels. Percentages of T-cell subsets and NK cells in
      blood were significantly increased after postoperative-week 1 as compared to
      preoperative group, which was further augmented at 1 month after gastrectomy. In
      addition, the expression of IL-6, survivin, STAT3, p-STAT3, and VEGF were
      increased in human gastric cancer tissues as compared to adjacent normal mucosa.
      Their expression was associated with TNM stage of gastric cancer. The level of
      STAT3 activation in clinical samples was correlated with IL-6 expression. All
      gastric tumor samples, which expressed p-STAT3, also expressed IL-6 with weak
      expression detected in adjacent normal mucosa. CONCLUSION: Increased IL-6-induced
      activation of STAT3 was observed in neoplastic gastric tissue, which positively
      correlated with tumor progression. Moreover, IL-6 and STAT3 downstream signals
      such as IL-10 and VEGF were reduced in patients after removal of gastric cancer
      as compared to pre-operation. Therefore, inhibition of the IL-6/STAT3 signaling
      pathway may provide a new therapeutic strategy against gastric cancer.

PMID- 24116075
TI  - Accuracy of glenoid component placement in total shoulder arthroplasty and its
      effect on clinical and radiological outcome in a retrospective, longitudinal,
      monocentric open study.
AB  - BACKGROUND: The success of Total Shoulder Arthroplasty (TSA) is believed to
      depend on the restoration of the natural anatomy of the joint and a key
      development has been the introduction of modular humeral components to more
      accurately restore the patient's anatomy. However, there are no peer-reviewed
      studies that have reported the degree of glenoid component mal-position achieved
      in clinical practice and the clinical outcome of such mal-position. The main
      purpose of this study was to assess the accuracy of glenoid implant positioning
      during TSA and to relate it to the radiological (occurrence of radiolucent lines
      and osteolysis on CT) and clinical outcomes. METHODS: 68 TSAs were assessed with
      a mean follow-up of 38+/-27 months. The clinical evaluation consisted of
      measuring the mobility as well as of the Constant Score. The radiological
      evaluation was performed on CT-scans in which metal artefacts had been
      eliminated. From the CT-scans radiolucent lines and osteolysis were assessed. The
      positions of the glenoid and humeral components were also measured from the CT
      scans. RESULTS: Four position glenoid component parameters were calculated The
      posterior version (6 degrees +/-12 degrees ; mean +/- SD), the superior tilt (12
      degrees +/-17 degrees ), the rotation of the implant relative to the scapular
      plane (3 degrees +/-14 degrees ) and the off-set distance of the centre of the
      glenoid implant from the scapular plane (6+/-4 mm). An inferiorly inclined
      implant was found to be associated with higher levels of radiolucent lines while
      retroversion and non-neutral rotation were associated with a reduced range of
      motion. CONCLUSION: this study demonstrates that glenoid implants of anatomic TSA
      are poorly positioned and that this malposition has a direct effect on the
      clinical and radiological outcome. Thus, further developments in glenoid
      implantation techniques are required to enable the surgeon to achieve a desired
      implant position and outcome.

PMID- 24116076
TI  - Multilocus sequence analysis of nectar pseudomonads reveals high genetic
      diversity and contrasting recombination patterns.
AB  - The genetic and evolutionary relationships among floral nectar-dwelling
      Pseudomonas 'sensu stricto' isolates associated to South African and
      Mediterranean plants were investigated by multilocus sequence analysis (MLSA) of
      four core housekeeping genes (rrs, gyrB, rpoB and rpoD). A total of 35 different
      sequence types were found for the 38 nectar bacterial isolates characterised.
      Phylogenetic analyses resulted in the identification of three main clades [nectar
      groups (NGs) 1, 2 and 3] of nectar pseudomonads, which were closely related to
      five intrageneric groups: Pseudomonas oryzihabitans (NG 1); P. fluorescens, P.
      lutea and P. syringae (NG 2); and P. rhizosphaerae (NG 3). Linkage disequilibrium
      analysis pointed to a mostly clonal population structure, even when the analysis
      was restricted to isolates from the same floristic region or belonging to the
      same NG. Nevertheless, signatures of recombination were observed for NG 3, which
      exclusively included isolates retrieved from the floral nectar of insect
      pollinated Mediterranean plants. In contrast, the other two NGs comprised both
      South African and Mediterranean isolates. Analyses relating diversification to
      floristic region and pollinator type revealed that there has been more unique
      evolution of the nectar pseudomonads within the Mediterranean region than would
      be expected by chance. This is the first work analysing the sequence of multiple
      loci to reveal geno- and ecotypes of nectar bacteria. 

PMID- 24116077
TI  - Performance comparison of digital microRNA profiling technologies applied on
      human breast cancer cell lines.
AB  - MicroRNA profiling represents an important first-step in deducting individual RNA
      based regulatory function in a cell, tissue, or at a specific developmental
      stage. Currently there are several different platforms to choose from in order to
      make the initial miRNA profiles. In this study we investigate recently developed
      digital microRNA high-throughput technologies. Four different platforms were
      compared including next generation SOLiD ligation sequencing and Illumina HiSeq
      sequencing, hybridization-based NanoString nCounter, and miRCURY locked nucleic
      acid RT-qPCR. For all four technologies, full microRNA profiles were generated
      from human cell lines that represent noninvasive and invasive tumorigenic breast
      cancer. This study reports the correlation between platforms, as well as a more
      extensive analysis of the accuracy and sensitivity of data generated when using
      different platforms and important consideration when verifying results by the use
      of additional technologies. We found all the platforms to be highly capable for
      microRNA analysis. Furthermore, the two NGS platforms and RT-qPCR all have
      equally high sensitivity, and the fold change accuracy is independent of
      individual miRNA concentration for NGS and RT-qPCR. Based on these findings we
      propose new guidelines and considerations when performing microRNA profiling. 

PMID- 24116079
TI  - Social insects dominate eastern US temperate hardwood forest macroinvertebrate
      communities in warmer regions.
AB  - Earthworms, termites, and ants are common macroinvertebrates in terrestrial
      environments, although for most ecosystems data on their abundance and biomass is
      sparse. Quantifying their areal abundance is a critical first step in
      understanding their functional importance. We intensively sampled dead wood,
      litter, and soil in eastern US temperate hardwood forests at four sites, which
      span much of the latitudinal range of this ecosystem, to estimate the abundance
      and biomass m(-2) of individuals in macroinvertebrate communities.
      Macroinvertebrates, other than ants and termites, differed only slightly among
      sites in total abundance and biomass and they were similar in ordinal
      composition. Termites and ants were the most abundant macroinvertebrates in dead
      wood, and ants were the most abundant in litter and soil. Ant abundance and
      biomass m(-2) in the southernmost site (Florida) were among the highest values
      recorded for ants in any ecosystem. Ant and termite biomass and abundance varied
      greatly across the range, from <1% of the total macroinvertebrate abundance (in
      the northern sites) to >95% in the southern sites. Our data reveal a pronounced
      shift to eusocial insect dominance with decreasing latitude in a temperate
      ecosystem. The extraordinarily high social insect relative abundance outside of
      the tropics lends support to existing data suggesting that ants, along with
      termites, are globally the most abundant soil macroinvertebrates, and surpass the
      majority of other terrestrial animal (vertebrate and invertebrate) groups in
      biomass m(-2). Our results provide a foundation for improving our understanding
      of the functional role of social insects in regulating ecosystem processes in
      temperate forest. 

PMID- 24116078
TI  - Effect of carbon monoxide-releasing molecules II-liberated CO on suppressing
      inflammatory response in sepsis by interfering with nuclear factor kappa B
      activation.
AB  - Sepsis continues to be a challenge in clinic. The rates of mortality in sepsis
      patients remain high. The present study aimed to investigate the effects and the
      underlying mechanisms of carbon monoxide-releasing molecules II (CORM-2)
      liberated CO on suppressing inflammatory response in sepsis. It was shown that
      treatment of septic mice with CORM-2 attenuated PMN accumulation, downregulated
      cytokines production, inhibited expressions of iNOS and NF-kappaB activity in the
      lung and liver. In parallel, CORM-2 prevented activation of NF-kappaB in LPS
      stimulated HUVEC. This was accompanied by a decrease in ROS and NO production,
      expression of ICAM-1 and subsequent PMN adhesion to HUVEC. These findings
      demonstrated that CORM-released CO attenuates inflammatory responses by
      interfering with NF-kappaB activation and therefore decreasing the expression of
      ICAM-1 and NO production, attenuating the oxidative stress and inflammation in
      sepsis. 

PMID- 24116080
TI  - Increased renal iron accumulation in hypertensive nephropathy of salt-loaded
      hypertensive rats.
AB  - Although iron is reported to be associated with the pathogenesis of chronic
      kidney disease, it is unknown whether iron participates in the pathophysiology of
      nephrosclerosis. Here, we investigate whether iron is involved in the development
      of hypertensive nephropathy and the effects of iron restriction on
      nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats
      (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another
      subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a
      high-salt diet developed severe hypertension and nephrosclerosis. As a result,
      survival rate was decreased after 8 weeks diet. Importantly, massive iron
      accumulation and increased iron content were observed in the kidneys of salt
      loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2'
      deoxyguanosine excretion, and urinary iron excretion; however, these changes were
      markedly attenuated by iron restriction. Of interest, expression of cellular iron
      transport proteins, transferrin receptor 1 and divalent metal transporter 1, was
      increased in the tubules of salt-loaded SHRSP. Notably, iron restriction
      attenuated the development of severe hypertension and nephrosclerosis, thereby
      improving survival rate in salt-loaded SHRSP. Taken together, these results
      suggest a novel mechanism by which iron plays a role in the development of
      hypertensive nephropathy and establish the effects of iron restriction on salt
      induced nephrosclerosis. 

PMID- 24116081
TI  - A single hot event that does not affect survival but decreases reproduction in
      the diamondback moth, Plutella xylostella.
AB  - Extremely hot events (usually involving a few hours at extreme high temperatures
      in summer) are expected to increase in frequency in temperate regions under
      global warming. The impact of these events is generally overlooked in insect
      population prediction, since they are unlikely to cause widespread mortality,
      however reproduction may be affected by them. In this study, we examined such
      stress effects in the diamondback moth, Plutella xylostella. We simulated a
      single extreme hot day (maximum of 40 degrees C lasting for 3, 4 or 5 h)
      increasingly experienced under field conditions. This event had no detrimental
      effects on immediate mortality, copulation duration, mating success, longevity or
      lifetime fecundity, but stressed females produced 21% (after 3 or 4 h) fewer
      hatched eggs because of a decline in the number and hatching success of eggs laid
      on the first two days. These negative effects on reproduction were no longer
      evident in the following days. Male heat exposure led to a similar but smaller
      effect on fertile egg production, and exposure extended pre-mating period in both
      sexes. Our results indicate that a single hot day can have detrimental effects on
      reproduction, particularly through maternal effects on egg hatching, and thereby
      influence the population dynamics of diamondback moth. 

PMID- 24116082
TI  - Assessing social engagement in heterogeneous groups of zebrafish: a new paradigm
      for autism-like behavioral responses.
AB  - Because of its highly developed social character, zebrafish is a promising model
      system for the study of the genetic and neurochemical basis of altered social
      engagement such as is common in autism and schizophrenia. The traditional
      shoaling paradigm investigates social cohesion in homogeneous groups of
      zebrafish. However, the social dynamics of mixed groups is gaining interest from
      a therapeutic point of view and thus warrants animal modeling. Furthermore,
      mutant zebrafish are not always available in large numbers. Therefore, we
      developed a new paradigm that allows exploring shoaling in heterogeneous groups.
      The effects of MK-801, a non-competitive antagonist of the glutamate N-methyl-D
      aspartate (NMDA) receptor, on social cohesion were studied to evaluate the
      paradigm. The drug has previously been shown to mimic aspects of autism and
      schizophrenia. Our results show that a single MK-801-treated zebrafish reduced
      social cohesion of the entire shoal drastically. Preliminary observations suggest
      that the social dynamics of the shoal as a whole was altered. 

PMID- 24116083
TI  - Biotic and abiotic soil properties influence survival of Listeria monocytogenes
      in soil.
AB  - Listeria monocytogenes is a food-borne pathogen responsible for the potentially
      fatal disease listeriosis and terrestrial ecosystems have been hypothesized to be
      its natural reservoir. Therefore, identifying the key edaphic factors that
      influence its survival in soil is critical. We measured the survival of L.
      monocytogenes in a set of 100 soil samples belonging to the French Soil Quality
      Monitoring Network. This soil collection is meant to be representative of the
      pedology and land use of the whole French territory. The population of L.
      monocytogenes in inoculated microcosms was enumerated by plate count after 7, 14
      and 84 days of incubation. Analysis of survival profiles showed that L.
      monocytogenes was able to survive up to 84 days in 71% of the soils tested, in
      the other soils (29%) only a short-term survival (up to 7 to 14 days) was
      observed. Using variance partitioning techniques, we showed that about 65% of the
      short-term survival ratio of L. monocytogenes in soils was explained by the soil
      chemical properties, amongst which the basic cation saturation ratio seems to be
      the main driver. On the other hand, while explaining a lower amount of survival
      ratio variance (11%), soil texture and especially clay content was the main
      driver of long-term survival of L. monocytogenes in soils. In order to assess the
      effect of the endogenous soils microbiota on L. monocytogenes survival,
      sterilized versus non-sterilized soils microcosms were compared in a subset of 9
      soils. We found that the endogenous soil microbiota could limit L. monocytogenes
      survival especially when soil pH was greater than 7, whereas in acidic soils,
      survival ratios in sterilized and unsterilized microcosms were not statistically
      different. These results point out the critical role played by both the
      endogenous microbiota and the soil physic-chemical properties in determining the
      survival of L. monocytogenes in soils. 

PMID- 24116084
TI  - Development of a cost-effective method for capripoxvirus genotyping using
      snapback primer and dsDNA intercalating dye.
AB  - Sheep pox virus (SPPV), goat pox virus (GTPV) and lumpy skin disease virus (LSDV)
      are very closely related viruses of the Capripoxvirus (CaPV) genus of the
      Poxviridae family. They are responsible for sheep pox, goat pox and lumpy skin
      disease which affect sheep, goat and cattle, respectively. The epidemiology of
      capripox diseases is complex, as some CaPVs are not strictly host-specific.
      Additionally, the three forms of the disease co-exist in many sub-Saharan
      countries which complicates the identification of the virus responsible for an
      outbreak. Genotyping of CaPVs using a low-cost, rapid, highly specific, and easy
      to perform method allows a swift and accurate identification of the causative
      agent and significantly assists in selecting appropriate control and eradication
      measures, such as the most suitable vaccine against the virus during the
      outbreaks. The objective of this paper is to describe the design and analytical
      performances of a new molecular assay for CaPV genotyping using unlabelled
      snapback primers in the presence of dsDNA intercalating EvaGreen dye. This assay
      was able to simultaneously detect and genotype CaPVs in 63 samples with a
      sensitivity and specificity of 100%. The genotyping was achieved by observing the
      melting temperature of snapback stems of the hairpins and those of the full
      length amplicons, respectively. Fourteen CaPVs were genotyped as SPPVs, 25 as
      GTPVs and 24 as LSDVs. The method is highly pathogen specific and cross platform
      compatible. It is also cost effective as it does not use fluorescently labelled
      probes, nor require high-resolution melting curve analysis software. Thus it can
      be easily performed in diagnostic and research laboratories with limited
      resources. This genotyping method will contribute significantly to the early
      detection and genotyping of CaPV infection and to epidemiological studies. 

PMID- 24116085
TI  - Identification and characterization of a cold-active phthalate esters hydrolase
      by screening a metagenomic library derived from biofilms of a wastewater
      treatment plant.
AB  - A cold-active phthalate esters hydrolase gene (designated dphB) was identified
      through functional screening of a metagenomic library derived from biofilms of a
      wastewater treatment plant. The enzyme specifically catalyzed the hydrolysis of
      dipropyl phthalate, dibutyl phthalate, and dipentyl phthalate to the
      corresponding monoalkyl phthalate esters at low temperatures. The catalytic triad
      residues of DphB were proposed to be Ser159, Asp251, and His281. 

PMID- 24116086
TI  - Adjusting the balance between effective loading and vector migration of
      macrophage vehicles to deliver nanoparticles.
AB  - The nature of macrophage allows the possibility that this cell type could be used
      as drug delivery system to track therapeutic drug nanoparticles (NPs) in cancer.
      However, there is no existing research on the regulation between effective
      loading of NPs and targeted delivery of macrophages. Here, we investigated the
      important parameters of intracellular NP quantity and the vector migration rate.
      Macrophage loading capacity was obtained by comparing the uptake quantity of
      varisized NPs, and the delivery ability of loaded cells was determined by
      measuring vector migration rates. We observed a positive correlation between the
      size of NPs and directed macrophage migration. Our findings suggest that the
      molecular mechanism of migration vector rate regulation involved increased
      expression levels of colony-stimulating factor-1 (CSF-1) receptor and integrin
      induced by 100-nm and 500-nm particles. The ability of macrophages uptake to
      varisized NPs showed the opposite trend, with the increased vector rate of cell
      migration influenced by NPs. We are able to demonstrate the important balance
      between effective macrophage loading and targeted delivery. By adjusting the
      balance parameters, it will be possible to utilize NPs in macrophage-mediated
      disease diagnosis and therapy. 

PMID- 24116087
TI  - Molecular marker differences relate to developmental position and subsets of
      mesodiencephalic dopaminergic neurons.
AB  - The development of mesodiencephalic dopaminergic (mdDA) neurons located in the
      substantia nigra compacta (SNc) and ventral tegmental area (VTA) follow a number
      of stages marked by distinct events. After preparation of the region by signals
      that provide induction and patterning, several transcription factors have been
      identified, which are involved in specifying the neuronal fate of these cells.
      The specific vulnerability of SNc neurons is thought to root in these specific
      developmental programs. The present study examines the positions of young
      postmitotic mdDA neurons to relate developmental position to mdDA subset specific
      markers. MdDA neurons were mapped relative to the neuromeric domains (prosomeres
      1-3 (P1-3), midbrain, and hindbrain) as well as the longitudinal subdivisions
      (floor plate, basal plate, alar plate), as proposed by the prosomeric model. We
      found that postmitotic mdDA neurons are located mainly in the floorplate domain
      and very few in slightly more lateral domains. Moreover, mdDA neurons are present
      along a large proportion of the anterior/posterior axis extending from the
      midbrain to P3 in the diencephalon. The specific positions relate to some extent
      to the presence of specific subset markers as Ahd2. In the adult stage more of
      such subsets specific expressed genes are present and may represent a molecular
      map defining molecularly distinct groups of mdDA neurons. 

PMID- 24116088
TI  - Significant biochemical, biophysical and metabolic diversity in circulating human
      cord blood reticulocytes.
AB  - BACKGROUND: The transition from enucleated reticulocytes to mature normocytes is
      marked by substantial remodeling of the erythrocytic cytoplasm and membrane.
      Despite conspicuous changes, most studies describe the maturing reticulocyte as a
      homogenous erythropoietic cell type. While reticulocyte staging based on
      fluorescent RNA stains such as thiazole orange have been useful in a clinical
      setting; these 'sub-vital' stains may confound delicate studies on reticulocyte
      biology and may preclude their use in heamoparasite invasion studies. DESIGN AND
      METHODS: Here we use highly purified populations of reticulocytes isolated from
      cord blood, sorted by flow cytometry into four sequential subpopulations based on
      transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and
      CD71negative. Each of these subgroups was phenotyped in terms of their,
      morphology, membrane antigens, biomechanical properties and metabolomic profile.
      RESULTS: Superficially CD71high and CD71medium reticulocytes share a similar
      gross morphology (large and multilobular) when compared to the smaller, smooth
      and increasingly concave reticulocytes as seen in the in the CD71low and
      CD71negativesamples. However, between each of the four sample sets we observe
      significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor
      expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations.
      Interestingly increasing amounts of boric acid was found in the mature
      reticulocytes. CONCLUSIONS: Reticulocyte maturation is a dynamic and continuous
      process, confounding efforts to rigidly classify them. Certainly this study does
      not offer an alternative classification strategy; instead we used a
      nondestructive sampling method to examine key phenotypic changes of in
      reticulocytes. Our study emphasizes a need to focus greater attention on
      reticulocyte biology.

PMID- 24116089
TI  - Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum
      albumin: multiple spectroscopic and molecular modeling investigations.
AB  - Interaction of a pharmacologically important flavonoid, pinostrobin (PS) with the
      major transport protein of human blood circulation, human serum albumin (HSA) has
      been examined using a multitude of spectroscopic techniques and molecular docking
      studies. Analysis of the fluorescence quenching data showed a moderate binding
      affinity (1.03 * 10(5) M(-1) at 25 degrees C) between PS and HSA with a 1?1
      stoichiometry. Thermodynamic analysis of the binding data (DeltaS = +44.06 J mol(
      1) K(-1) and DeltaH = -15.48 kJ mol(-1)) and molecular simulation results
      suggested the involvement of hydrophobic and van der Waals forces, as well as
      hydrogen bonding in the complex formation. Both secondary and tertiary structural
      perturbations in HSA were observed upon PS binding, as revealed by intrinsic,
      synchronous, and three-dimensional fluorescence results. Far-UV circular
      dichroism data revealed increased thermal stability of the protein upon
      complexation with PS. Competitive drug displacement results suggested the binding
      site of PS on HSA as Sudlow's site I, located at subdomain IIA, and was well
      supported by the molecular modelling data. 

PMID- 24116090
TI  - Roles of adrenergic alpha1 and dopamine D1 and D2 receptors in the mediation of
      the desynchronization effects of modafinil in a mouse EEG synchronization model.
AB  - BACKGROUND: Synchronized electroencephalogram (EEG) activity is observed in
      pathological stages of cognitive impairment and epilepsy. Modafinil, known to
      increase the release of catecholamines, is a potent wake-promoting agent, and has
      shown some abilities to desynchronize EEG,but its receptor mechanisms by which
      modafinil induces desynchoronization remain to be elucidated. Here we used a
      pharmacological EEG synchronization model to investigate the involvement of
      adrenergic alpha1 receptors (R, alpha1R) and dopamine (DA) D1 and D2 receptors
      (D1Rs and D2Rs) on modafinil-induced desynchronization in mice.
      METHODOLOGY/PRINCIPAL FINDINGS: Mice were treated with cholinergic receptor
      antagonist scopolamine and monoamine depletor reserpine to produce experimental
      EEG synchronization characterized by continuous large-amplitude synchronized
      activity, with prominent increased delta and decreased theta, alpha, and beta
      power density. The results showed that modafinil produced an EEG
      desynchronization in the model. This was characterized by a general decrease in
      amplitude of all the frequency bands between 0 and 20 Hz, a prominent reduction
      in delta power density, and an increase in theta power density. Adrenergic
      alpha1R antagonist terazosin (1 mg/kg, i.p.) completely antagonized the EEG
      desynchronization effects of modafinil at 90 mg/kg. However, DA D1R and D2R
      blockers partially attenuated the effects of modafinil. The modafinil-induced
      decrease in the amplitudes of the delta, theta, alpha, and beta waves and in
      delta power density were completely abolished by pretreatment with a combination
      of the D1R antagonist SCH 23390 (30 ug/kg) and the D2R antagonist raclopride (2
      mg/kg, i.p.). CONCLUSIONS/SIGNIFICANCE: These results suggest that modafinil
      mediated desynchronization may be attributed to the activation of adrenergic
      alpha1R, and dopaminergic D1R and D2R in a model of EEG synchronization.

PMID- 24116091
TI  - Golden GATEway cloning--a combinatorial approach to generate fusion and
      recombination constructs.
AB  - The design and generation of DNA constructs is among the necessary but generally
      tedious tasks for molecular biologists and, typically, the cloning strategy is
      restricted by available restriction sites. However, increasingly sophisticated
      experiments require increasingly complex DNA constructs, with an intricacy that
      exceeds what is achievable using standard cloning procedures. Many transgenes
      such as inducible gene cassettes or recombination elements consist of multiple
      components that often require precise in-frame fusions. Here, we present an
      efficient protocol that facilitates the generation of these complex constructs.
      The golden GATEway cloning approach presented here combines two established
      cloning methods, namely golden Gate cloning and Multisite Gateway(TM) cloning.
      This allows efficient and seamless assembly as well as reuse of predefined DNA
      elements. The golden Gate cloning procedure follows clear and simple design rules
      and allows the assembly of multiple fragments with different sizes into one open
      reading frame. The final product can be directly integrated into the widely used
      Multisite Gateway(TM) cloning system, granting more flexibility when using a
      transgene in the context of multiple species. This adaptable and streamlined
      cloning procedure overcomes restrictions of "classical construct generation" and
      allows focusing on construct design. 

PMID- 24116092
TI  - An animal explant model for the study of human cutaneous squamous cell carcinoma.
AB  - We established a human tissue explant model to facilitate study of cutaneous
      squamous cell carcinoma. We accomplished this by implanting debulked SCC, from
      surgical discard, into nude rats. Human SCC remained viable and continued to
      proliferate for at least 4 weeks and showed evidence of neovascularization. At 4
      weeks, SCC implants showed a trend toward increased PCNA positive cells compared
      to fresh SCC cells/mm(2) tissue) supporting continued proliferation throughout
      engraftment. Von Willebrand's Factor (VWF) positive cells were found within
      implants and likely represented rat vessel neovascularization. Human Langerhans'
      (Langerin+) cells, but no T cells (CD3+, CD8+, FoxP3+), macrophages (CD163), or
      NK cells (NKp46), were present in SCC implants at 4 weeks. These findings support
      the possibility that LCs fail to migrate from cutaneous SCC and thus contribute
      to lack of effective antitumor response. Our findings also provide a novel model
      system for further study of primary cutaneous SCC. 

PMID- 24116093
TI  - Expression and function of Allergin-1 on human primary mast cells.
AB  - Mast cells (MC) play an important role in allergic and non-allergic immune
      responses. Activation of human MC is modulated by several cell surface inhibitory
      receptors, including recently identified Allergin-1 expressed on both human and
      mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent
      anaphylaxis in mice, the expression profile and function of Allergin-1 on human
      primary MC remains undetermined. Here, we established a seven-color flow
      cytometry method for assessing expression and function of a very small number of
      human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is
      predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL)
      fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE
      mediated activation from human primary MC in BAL fluid. These results indicate
      that Allergin-1 on human primary MC exhibits similar characteristics as mouse
      Allergin-1 in the expression profile and function. 

PMID- 24116094
TI  - scnRCA: a novel method to detect consistent patterns of translational selection
      in mutationally-biased genomes.
AB  - Codon usage bias (CUB) results from the complex interplay between translational
      selection and mutational biases. Current methods for CUB analysis apply
      heuristics to integrate both components, limiting the depth and scope of CUB
      analysis as a technique to probe into the evolution and optimization of protein
      coding genes. Here we introduce a self-consistent CUB index (scnRCA) that
      incorporates implicit correction for mutational biases, facilitating exploration
      of the translational selection component of CUB. We validate this technique using
      gene expression data and we apply it to a detailed analysis of CUB in the
      Pseudomonadales. Our results illustrate how the selective enrichment of specific
      codons among highly expressed genes is preserved in the context of genome-wide
      shifts in codon frequencies, and how the balance between mutational and
      translational biases leads to varying definitions of codon optimality. We extend
      this analysis to other moderate and fast growing bacteria and we provide unified
      support for the hypothesis that C- and A-ending codons of two-box amino acids,
      and the U-ending codons of four-box amino acids, are systematically enriched
      among highly expressed genes across bacteria. The use of an unbiased estimator of
      CUB allows us to report for the first time that the signature of translational
      selection is strongly conserved in the Pseudomonadales in spite of drastic
      changes in genome composition, and extends well beyond the core set of highly
      optimized genes in each genome. We generalize these results to other moderate and
      fast growing bacteria, hinting at selection for a universal pattern of gene
      expression that is conserved and detectable in conserved patterns of codon usage
      bias. 

PMID- 24116095
TI  - Multimodal assessment of long-term memory recall and reinstatement in a combined
      cue and context fear conditioning and extinction paradigm in humans.
AB  - Learning to predict danger via associative learning processes is critical for
      adaptive behaviour. After successful extinction, persisting fear memories often
      emerge as returning fear. Investigation of return of fear phenomena, e.g.
      reinstatement, have only recently began and to date, many critical questions with
      respect to reinstatement in human populations remain unresolved. Few studies have
      separated experimental phases in time even though increasing evidence shows that
      allowing for passage of time (and consolidation) between experimental phases has
      a major impact on the results. In addition, studies have relied on a single
      psychophysiological dimension only (SCRs/SCL or FPS) which hampers comparability
      between different studies that showed both differential or generalized return of
      fear following a reinstatement manipulation. In 93 participants, we used a
      multimodal approach (fear-potentiated startle, skin conductance responses, fear
      ratings to asses fear conditioning (day 1), extinction (day 2) as well as delayed
      memory recall and reinstatement (day 8) in a paradigm that probed contextual and
      cued fear intra-individually. Our findings show persistence of conditioning and
      extinction memory over time and demonstrate that reinstated fear responses were
      qualitatively different between dependent variables (subjective fear ratings,
      FPS, SCRs) as well as between cued and contextual CSs. While only the arousal
      related measurement (SCRs) showed increasing reactions following reinstatement to
      the cued CSs, no evidence of reinstatement was observed for the subjective
      ratings and fear-related measurement (FPS). In contrast, for contextual CSs,
      reinstatement was evident as differential and generalized reinstatement in fear
      ratings as well as generally elevated physiological fear (FPS) and arousal (SCRs)
      related measurements to all contextual CSs (generalized non-differential
      reinstatement). Returning fear after reinstatement likely depends on a variety of
      variables (experimental design, dependent measurements) and more systematic
      investigations with respect to critical determinants of reinstatement in humans
      are required. 

PMID- 24116096
TI  - Giardia lamblia transcriptome analysis using TSS-Seq and RNA-Seq.
AB  - Giardia lamblia is a protozoan parasite that is found worldwide and has both
      medical and veterinary importance. We applied the transcription start sequence
      (TSS-seq) and RNA sequence (RNA-seq) techniques to study the transcriptome of the
      assemblage A WB strain trophozoite. We identified 8000 transcription regions (TR)
      with significant transcription. Of these regions, 1881 TRs were more than 500
      nucleotides upstream of an annotated ORF. Combining both techniques helped us to
      identify 24 ORFs that should be re-annotated and 60 new ORFs. From the 8000 TRs,
      we were able to identify an AT-rich consensus that includes the transcription
      initiation site. It is possible that transcription that was previously thought to
      be bidirectional is actually unidirectional. 

PMID- 24116097
TI  - Sulfamethoxazole induces a switch mechanism in T cell receptors containing
      TCRVbeta20-1, altering pHLA recognition.
AB  - T cell receptors (TCR) containing Vbeta20-1 have been implicated in a wide range
      of T cell mediated disease and allergic reactions, making it a target for
      understanding these. Mechanics of T cell receptors are largely unexplained by
      static structures available from x-ray crystallographic studies. A small number
      of molecular dynamic simulations have been conducted on TCR, however are
      currently lacking either portions of the receptor or explanations for differences
      between binding and non-binding TCR recognition of respective peptide-HLA. We
      performed molecular dynamic simulations of a TCR containing variable domain
      Vbeta20-1, sequenced from drug responsive T cells. These were initially from a
      patient showing maculopapular eruptions in response to the sulfanilamide
      antibiotic sulfamethoxazole (SMX). The CDR2beta domain of this TCR was found to
      dock SMX with high affinity. Using this compound as a perturbation, overall
      mechanisms involved in responses mediated by this receptor were explored, showing
      a chemical action on the TCR free from HLA or peptide interaction. Our
      simulations show two completely separate modes of binding cognate peptide-HLA
      complexes, with an increased affinity induced by SMX bound to the Vbeta20-1.
      Overall binding of the TCR is mediated through a primary recognition by either
      the variable beta or alpha domain, and a switch in recognition within these
      across TCR loops contacting the peptide and HLA occurs when SMX is present in the
      CDR2beta loop. Large binding affinity differences are induced by summed small
      amino acid changes primarily by SMX modifying only three critical CDR2beta loop
      amino acid positions. These residues, TYRbeta57, ASPbeta64, and LYSbeta65
      initially hold hydrogen bonds from the CDR2beta to adjacent CDR loops. Effects
      from SMX binding are amplified and traverse longer distances through internal TCR
      hydrogen bonding networks, controlling the overall TCR conformation. Thus, the
      CDR2beta of Vbeta20-1 acts as a ligand controlled switch affecting overall TCR
      binding affinity. 

PMID- 24116098
TI  - A cocktail of thermally stable, chemically synthesized capture agents for the
      efficient detection of anti-gp41 antibodies from human sera.
AB  - We report on a method to improve in vitro diagnostic assays that detect immune
      response, with specific application to HIV-1. The inherent polyclonal diversity
      of the humoral immune response was addressed by using sequential in situ click
      chemistry to develop a cocktail of peptide-based capture agents, the components
      of which were raised against different, representative anti-HIV antibodies that
      bind to a conserved epitope of the HIV-1 envelope protein gp41. The cocktail was
      used to detect anti-HIV-1 antibodies from a panel of sera collected from HIV
      positive patients, with improved signal-to-noise ratio relative to the gold
      standard commercial recombinant protein antigen. The capture agents were stable
      when stored as a powder for two months at temperatures close to 60(o)C. 

PMID- 24116099
TI  - Real-time electrical impedimetric monitoring of blood coagulation process under
      temperature and hematocrit variations conducted in a microfluidic chip.
AB  - Blood coagulation is an extremely complicated and dynamic physiological process.
      Monitoring of blood coagulation is essential to predict the risk of hemorrhage
      and thrombosis during cardiac surgical procedures. In this study, a high
      throughput microfluidic chip has been developed for the investigation of the
      blood coagulation process under temperature and hematocrit variations. Electrical
      impedance of the whole blood was continuously recorded by on-chip electrodes in
      contact with the blood sample during coagulation. Analysis of the impedance
      change of the blood was conducted to investigate the characteristics of blood
      coagulation process and the starting time of blood coagulation was defined. The
      study of blood coagulation time under temperature and hematocrit variations was
      shown a good agreement with results in the previous clinical reports. The
      electrical impedance measurement for the definition of blood coagulation process
      provides a fast and easy measurement technique. The microfluidic chip was shown
      to be a sensitive and promising device for monitoring blood coagulation process
      even in a variety of conditions. It is found valuable for the development of
      point-of-care coagulation testing devices that utilizes whole blood sample in
      microliter quantity. 

PMID- 24116101
TI  - Structure before meaning: sentence processing, plausibility, and
      subcategorization.
AB  - Natural language processing is a fast and automatized process. A crucial part of
      this process is parsing, the online incremental construction of a syntactic
      structure. The aim of this study was to test whether a wh-filler extracted from
      an embedded clause is initially attached as the object of the matrix verb with
      subsequent reanalysis, and if so, whether the plausibility of such an attachment
      has an effect on reaction time. Finally, we wanted to examine whether
      subcategorization plays a role. We used a method called G-Maze to measure
      response time in a self-paced reading design. The experiments confirmed that
      there is early attachment of fillers to the matrix verb. When this attachment is
      implausible, the off-line acceptability of the whole sentence is significantly
      reduced. The on-line results showed that G-Maze was highly suited for this type
      of experiment. In accordance with our predictions, the results suggest that the
      parser ignores (or has no access to information about) implausibility and
      attaches fillers as soon as possible to the matrix verb. However, the results
      also show that the parser uses the subcategorization frame of the matrix verb. In
      short, the parser ignores semantic information and allows implausible attachments
      but adheres to information about which type of object a verb can take, ensuring
      that the parser does not make impossible attachments. We argue that the evidence
      supports a syntactic parser informed by syntactic cues, rather than one guided by
      semantic cues or one that is blind, or completely autonomous. 

PMID- 24116100
TI  - NMK-TD-100, a novel microtubule modulating agent, blocks mitosis and induces
      apoptosis in HeLa cells by binding to tubulin.
AB  - Thiadiazoles are one of the most widely utilized agents in medicinal chemistry,
      having a wide range of pharmacologic activity. Microtubules (MTs) have always
      remained a sought-after target in rapidly proliferating cancer cells. We screened
      for the growth inhibitory effect of synthetic 5-(3-indolyl)-2-substituted-1,3,4
      thiadiazoles on cancer cells and identified NMK-TD-100, as the most potent agent.
      Cell viability experiments using human cervical carcinoma cell line (HeLa cells)
      indicated that the IC50 value was 1.42+/-0.11 uM for NMK-TD-100 for 48 h
      treatment. In further study, we examined the mode of interaction of NMK-TD-100
      with tubulin and unraveled the cellular mechanism responsible for its anti-tumor
      activity. NMK-TD-100 induced arrest in mitotic phase of cell cycle, caused
      decline in mitochondrial membrane potential and induced apoptosis in HeLa cells.
      Immunofluorescence studies using an anti-alpha-tubulin antibody showed a
      significant depolymerization of the interphase microtubule network and spindle
      microtubule in HeLa cells in a concentration-dependent manner. However, the
      cytotoxicity of NMK-TD-100 towards human peripheral blood mononuclear cells
      (PBMC) was lower compared to that in cancer cells. Polymerization of tissue
      purified tubulin into microtubules was inhibited by NMK-TD-100 with an IC50 value
      of 17.5+/-0.35 uM. The binding of NMK-TD-100 with tubulin was studied using NMK
      TD-100 fluorescence enhancement and intrinsic tryptophan fluorescence of tubulin.
      The stoichiometry of NMK-TD-100 binding to tubulin is 1:1 (molar ratio) with a
      dissociation constant of ~1 uM. Fluorescence spectroscopic and molecular modeling
      data showed that NMK-TD-100 binds to tubulin at a site which is very near to the
      colchicine binding site. The binding of NMK-TD-100 to tubulin was estimated to be
      ~10 times faster than that of colchicine. The results indicated that NMK-TD-100
      exerted anti-proliferative activity by disrupting microtubule functions through
      tubulin binding and provided insights into its potential of being a
      chemotherapeutic agent. 

PMID- 24116102
TI  - Sox2 expression is regulated by a negative feedback loop in embryonic stem cells
      that involves AKT signaling and FoxO1.
AB  - The self-renewal and pluripotency of embryonic stem cells (ESC) is regulated by a
      highly integrated network of essential transcription factors, which includes
      Sox2. Previous studies have shown that elevating Sox2 on its own in mouse ESC
      induces differentiation and inhibits the expression of endogenous Sox2 at the
      protein and mRNA level. These findings led us to hypothesize that increases in
      Sox2 activate a negative feedback loop that inhibits the transcription of the
      endogenous Sox2 gene. To test this hypothesis, we used i-OSKM-ESC, which elevate
      Sox2 in conjunction with Oct4, Klf4, and c-Myc when treated with doxycycline
      (Dox). Elevating the expression of these four transcription factors in i-OSKM-ESC
      does not induce differentiation, but it represses expression of endogenous Sox2.
      We determined that increases of Sox2 in i-OSKM-ESC lead to increases in activated
      AKT and inactivation of FoxO1 (an activator of Sox2), as well as decreases in
      binding of FoxO1 to the 5'flanking region of Sox2. Importantly, we determined
      that inhibition of AKT in Dox-treated i-OSKM-ESC leads to re-expression of
      endogenous Sox2 at the mRNA and protein level and reactivation of FoxO1. These
      findings argue that AKT signaling is part of the negative feedback loop that
      helps carefully control the transcription of Sox2 in ESC by modulating the
      binding of FoxO1 to the Sox2 gene. Collectively, our findings provide new
      insights into the mechanisms that enable ESC to carefully regulate the levels of
      Sox2 and retain their stem cell properties. 

PMID- 24116103
TI  - Genetic interactions between Brn3 transcription factors in retinal ganglion cell
      type specification.
AB  - BACKGROUND: Visual information is conveyed from the retina to the brain via 15-20
      Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC
      types acquire their distinct molecular, morphological, physiological and circuit
      properties are essentially unknown, but may involve combinatorial transcriptional
      regulation. Brn3 transcription factors are expressed in RGCs from early
      developmental stages, and are restricted in adults to distinct, partially
      overlapping populations of RGC types. Previously, we described cell autonomous
      effects of Brn3b (Pou4f2) and Brn3a (Pou4f1) on RGC axon and dendrites
      development. METHODS AND FINDINGS: We now have investigated genetic interactions
      between Brn3 transcription factors with respect to RGC development, by crossing
      conventional knock-out alleles of each Brn3 gene with conditional knock-in
      reporter alleles of a second Brn3 gene, and analyzing the effects of single or
      double Brn3 knockouts on RGC survival and morphology. We find that Brn3b loss
      results in axon defects and dendritic arbor area and lamination defects in Brn3a
      positive RGCs, and selectively affects survival and morphology of specific Brn3c
      (Pou4f3) positive RGC types. Brn3a and Brn3b interact synergistically to control
      RGC numbers. Melanopsin positive ipRGCs are resistant to combined Brn3 loss but
      are under the transcriptional control of Isl1, expanding the combinatorial code
      of RGC specification. CONCLUSIONS: Taken together these results complete our
      knowledge on the mechanisms of transcriptional control of RGC type specification.
      They demonstrate that Brn3b is required for the correct development of more RGC
      cell types than suggested by its expression pattern in the adult, but that
      several cell types, including some Brn3a, Brn3c or Melanopsin positive RGCs are
      Brn3b independent.

PMID- 24116104
TI  - The impact of Helicobacter pylori infection on the gastric microbiota of the
      rhesus macaque.
AB  - Helicobacter pylori colonization is highly prevalent among humans and causes
      significant gastric disease in a subset of those infected. When present, this
      bacterium dominates the gastric microbiota of humans and induces antimicrobial
      responses in the host. Since the microbial context of H. pylori colonization
      influences the disease outcome in a mouse model, we sought to assess the impact
      of H. pylori challenge upon the pre-existing gastric microbial community members
      in the rhesus macaque model. Deep sequencing of the bacterial 16S rRNA gene
      identified a community profile of 221 phylotypes that was distinct from that of
      the rhesus macaque distal gut and mouth, although there were taxa in common. High
      proportions of both H. pylori and H. suis were observed in the post-challenge
      libraries, but at a given time, only one Helicobacter species was dominant.
      However, the relative abundance of non-Helicobacter taxa was not significantly
      different before and after challenge with H. pylori. These results suggest that
      while different gastric species may show competitive exclusion in the gastric
      niche, the rhesus gastric microbial community is largely stable despite immune
      and physiological changes due to H. pylori infection. 

PMID- 24116105
TI  - Limitations of airway dimension measurement on images obtained using multi
      detector row computed tomography.
AB  - OBJECTIVES: (a) To assess the effects of computed tomography (CT) scanners,
      scanning conditions, airway size, and phantom composition on airway dimension
      measurement and (b) to investigate the limitations of accurate quantitative
      assessment of small airways using CT images. METHODS: An airway phantom, which
      was constructed using various types of material and with various tube sizes, was
      scanned using four CT scanner types under different conditions to calculate
      airway dimensions, luminal area (Ai), and the wall area percentage (WA%). To
      investigate the limitations of accurate airway dimension measurement, we then
      developed a second airway phantom with a thinner tube wall, and compared the
      clinical CT images of healthy subjects with the phantom images scanned using the
      same CT scanner. The study using clinical CT images was approved by the local
      ethics committee, and written informed consent was obtained from all subjects.
      Data were statistically analyzed using one-way ANOVA. RESULTS: Errors noted in
      airway dimension measurement were greater in the tube of small inner radius made
      of material with a high CT density and on images reconstructed by body algorithm
      (p<0.001), and there was some variation in error among CT scanners under
      different fields of view. Airway wall thickness had the maximum effect on the
      accuracy of measurements with all CT scanners under all scanning conditions, and
      the magnitude of errors for WA% and Ai varied depending on wall thickness when
      airways of <1.0-mm wall thickness were measured. CONCLUSIONS: The parameters of
      airway dimensions measured were affected by airway size, reconstruction
      algorithm, composition of the airway phantom, and CT scanner types. In dimension
      measurement of small airways with wall thickness of <1.0 mm, the accuracy of
      measurement according to quantitative CT parameters can decrease as the walls
      become thinner.

PMID- 24116106
TI  - Effect of transcatheter intraarterial therapies on the distribution of
      Doxorubicin in liver cancer in a rabbit model.
AB  - BACKGROUND AND AIMS: Transcatheter intraarterial techniques can effectively
      deliver chemotherapeutic agents to tumor and improve the efficacy of
      chemotherapy. The present study is designed to evaluate the effect of
      transcatheter intraarterial techniques on the distribution of doxorubicin in
      relation to blood vessels in liver cancer. METHODS: VX2 tumors were implanted in
      the livers of 32 rabbits. The animals were divided into 4 groups of 8 animals
      each. Group 1 (doxo iv) animals received doxorubicin intravenous injection; group
      2 (doxo ia) received doxorubicin hepatic intraarterial infusion; group 3 (doxo ia
      + E) received doxorubicin hepatic intraarterial infusion followed by
      embolization; group 4 (doxo + L ia + E) received hepatic intraarterial infusion
      of doxorubicin mixed with Lipiodol followed by embolization. Ten minutes or 4
      hours after treatment, the animals were sacrificed and tumors were sampled.
      Immunofluorescence techniques were used to evaluate the distribution of
      doxorubicin in relation to blood vessels. RESULTS: Doxorubicin fluorescence was
      distributed around tumor blood vessels and decreased with distance from the blood
      vessels. Tumor cells in avascular and adjacent regions were not exposed to
      detectable concentrations of doxorubicin. Tumors in the group 2, 3 and 4 had a
      significant increase in doxorubicin penetration compared with the group 1 tumors
      (P<0.05). Among the three groups of transcatheter therapies, doxorubicin
      penetration distance in group 3 was significantly larger than that in group 2 and
      4 (P<0.05), and no significant difference was found between group 2 and 4 tumors
      (P>0.05) at 10 minutes. In contrast, at 4 hours and in total, both group 3 and 4
      tumors had significant increases in drug penetration compared with group 2
      (P<0.05), and no significant difference was noted between group 3 and 4 tumors
      (P>0.05). CONCLUSION: Transcatheter intraarterial therapies improve doxorubicin
      penetration in liver cancer; nevertheless their effect on drug distribution is
      somewhat limited.

PMID- 24116107
TI  - Increased risk of developing digestive tract cancer in subjects carrying the
      PLCE1 rs2274223 A>G polymorphism: evidence from a meta-analysis.
AB  - BACKGROUND: To date, the association between phospholipase C epsilon 1 (PLCE1)
      rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To
      derive a more precise estimation of the association, we conducted a meta-analysis
      on all eligible case-control studies involving 8281 cases and 10,532 controls.
      METHODS: A comprehensive search was conducted to identify all eligible studies of
      PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds
      ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed
      or random effect model. Heterogeneity, publication bias, and sensitivity analysis
      were also explored. RESULTS: Overall, the PLCE1 rs2274223 A>G polymorphism was
      associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI =
      1.14-1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06-1.60, P = 0.012; GG/GA
      vs. AA: OR = 1.20, 95% CI = 1.10-1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI =
      1.01-1.46, P = 0.040). The recessive model did not reach statistically
      significance when the P values were Bonferroni corrected to 0.0125. In the
      stratified analysis by cancer type, ethnicity, and source of controls,
      significantly increased risk was observed for esophagus cancer, Asians in three
      genetic models (heterozygote comparison, homozygote comparison and dominant
      model), population-based studies in all genetic models, and for gastric cancer in
      the heterozygote comparison and dominant model after Bonferroni correction.
      However, in the subsite of gastric cancer, no significant association was found
      either in cardia or non-cardia gastric cancer. CONCLUSION: Our study indicated
      that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased
      risk of DTC, especially among Asian populations. Due to some minor limitations,
      our findings should be confirmed in further studies.

PMID- 24116108
TI  - MglA/SspA complex interactions are modulated by inorganic polyphosphate.
AB  - The transcription factors MglA and SspA of Francisella tularensis form a
      heterodimer complex and interact with the RNA polymerase to regulate the
      expression of the Francisella pathogenicity island (FPI) genes. These genes are
      essential for this pathogen's virulence and survival within host cells. Our goal
      was to determine if an intracellular metabolite modulate these protein/protein
      interactions. In this study, we identified inorganic polyphosphate (polyP) as a
      signal molecule that promotes the interaction of MglA and SspA from F. tularensis
      SCHU S4. Analysis of the Mgla/SspA interaction was carried out using a two-hybrid
      system. The Escherichia coli reporter strain contained a deletion on the ppK-ppX
      operon, inhibiting polyP synthesis. The interaction between MglA and SspA was
      significantly impaired, as was the interaction between the MglA/SspA complex and
      the regulatory protein, FevR, indicating the stabilizing effect of polyP. In F.
      tularensis, chromatin immune precipitation studies revealed that in the absence
      of polyP, binding of the MglA/SspA complex to the promoter region of the pdpD,
      iglA, fevR and ppK genes is decreased. Isothermal titration calorimetry (ITC)
      indicated that polyP binds directly to the MglA/SspA complex with high affinity
      (KD = 0.3 uM). These observations directly correlated with results obtained from
      calorimetric scans (DSC), where a strong shift in the mid-transition temperature
      (Tm) of the MglA/SspA complex was observed in the presence of polyP. 

PMID- 24116109
TI  - Tolerance of sponge assemblages to temperature anomalies: resilience and
      proliferation of sponges following the 1997-8 El-Nino southern oscillation.
AB  - Coral reefs across the world are under threat from a range of stressors, and
      while there has been considerable focus on the impacts of these stressors on
      corals, far less is known about their effect on other reef organisms. The 1997-8
      El-Nino Southern Oscillation (ENSO) had notable and severe impacts on coral reefs
      worldwide, but not all reef organisms were negatively impacted by this large
      scale event. Here we describe how the sponge fauna at Bahia, Brazil was
      influenced by the 1997-8 ENSO event. Sponge assemblages from three contrasting
      reef habitats (reef tops, walls and shallow banks) at four sites were assessed
      annually from 1995 to 2011. The within-habitat sponge diversity did not vary
      significantly across the study period; however, there was a significant increase
      in density in all habitats. Multivariate analyses revealed no significant
      difference in sponge assemblage composition (ANOSIM) between pre- and post-ENSO
      years for any of the habitats, suggesting that neither the 1997-8 nor any
      subsequent smaller ENSO events have had any measurable impact on the reef sponge
      assemblage. Importantly, this is in marked contrast to the results previously
      reported for a suite of other taxa (including corals, echinoderms, bryozoans, and
      ascidians), which all suffered mass mortalities as a result of the ENSO event.
      Our results suggest that of all reef taxa, sponges have the potential to be
      resilient to large-scale thermal stress events and we hypothesize that sponges
      might be less affected by projected increases in sea surface temperature compared
      to other major groups of reef organisms. 

PMID- 24116110
TI  - The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in
      pancreatic cancer cell proliferation and decreased patient survival.
AB  - BACKGROUND: miR-26a plays a critical role in tumorigenesis, either as a tumor
      suppressor or as an oncogenic miRNA, depending on different tumor types. However,
      the function of miR-26a in pancreatic cancer has not been clearly elucidated. The
      present study was designed to determine the roles of miR-26a in pancreatic cancer
      and its association with the survival of patients with pancreatic cancer.
      METHODS: The expression of miR-26a was examined in 15 pairs of pancreatic duct
      adenocarcinoma (PDAC) and their adjacent benign pancreatic tissues (ABPT), by qRT
      PCR. The results were confirmed by in situ hybridization using two panels of 106
      PDACs and their ABPT microarray. The association of miR-26a expression with
      overall survival was determined. The proliferation and cell cycle distribution of
      Capan-2, SW-1990, and Panc-1 cells, transfected with miR-26a mimics or a miR-26a
      inhibitor, were assessed using the Cell Counting Kit-8 assay and flow cytometry,
      respectively. The cell tumorigenicity was evaluated via murine xenograft
      experiments. Cyclin D2, E2, EZH2, and PCNA levels were analyzed by Western blot
      and immunohistochemistry. RESULTS: miR-26a was expressed in the cytoplasm of
      pancreatic ductal epithelial cells, whereas its expression was significantly
      downregulated in PDAC tissues compared with that of ABPT. Patients with low miR
      26a expression had a significantly shorter survival than those with high miR-26a
      expression. The in vitro and in vivo assays showed that overexpression of miR-26a
      resulted in cell cycle arrest, inhibited cell proliferation, and decreased tumor
      growth, which was associated with cyclin E2 downregulation. CONCLUSIONS: miR-26a
      is an important suppressor of pancreatic ductal carcinoma, and can prove to be a
      novel prognostic factor and therapeutic target for pancreatic cancer treatment.

PMID- 24116112
TI  - North Atlantic blue and fin whales suspend their spring migration to forage in
      middle latitudes: building up energy reserves for the journey?
AB  - The need to balance energy reserves during migration is a critical factor for
      most long-distance migrants and an important determinant of migratory strategies
      in birds, insects and land mammals. Large baleen whales migrate annually between
      foraging and breeding sites, crossing vast ocean areas where food is seldom
      abundant. How whales respond to the demands and constraints of such long
      migrations remains unknown. We applied a behaviour discriminating hierarchical
      state-space model to the satellite tracking data of 12 fin whales and 3 blue
      whales tagged off the Azores, to investigate their movements, behaviour
      (transiting and area-restricted search, ARS) and daily activity cycles during the
      spring migration. Fin and blue whales remained at middle latitudes for prolonged
      periods, spending most of their time there in ARS behaviour. While near the
      Azores, fin whale ARS behaviour occurred within a restricted area, with a high
      degree of overlap among whales. There were noticeable behavioural differences
      along the migratory pathway of fin whales tracked to higher latitudes: ARS
      occurred only in the Azores and north of 56 degrees N, whereas in between these
      areas whales travelled at higher overall speeds while maintaining a nearly direct
      trajectory. This suggests fin whales may alternate periods of active migration
      with periods of extended use of specific habitats along the migratory route. ARS
      behaviour in blue whales occurred over a much wider area as whales slowly
      progressed northwards. The tracks of these whales terminated still at middle
      latitudes, before any behavioural switch was detected. Fin whales exhibited
      behavioural-specific diel rhythms in swimming speed but these varied
      significantly between geographic areas, possibly due to differences in the day
      night cycle across areas. Finally, we show a link between fin whales seen in the
      Azores and those summering in eastern Greenland-western Iceland along a migratory
      corridor located in central Atlantic waters. 

PMID- 24116111
TI  - Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV
      1 strains in primary PBMCs and cervicovaginal histocultures.
AB  - Peptide dendrimers are a class of molecules that exhibit a large array of
      biological effects including antiviral activity. In this report, we analyzed the
      antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a
      tetra-branched dendrimer synthetized on a lysine core, in activated peripheral
      blood mononuclear cells (PBMCs) that were challenged with reference and wild-type
      human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited
      infections by HIV-1 X4 and R5 strains, interfering with the early phases of the
      viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs)
      and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105
      A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry
      through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10
      was also detectable in an organ-like structure of human cervicovaginal tissue, in
      which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the
      tissue viability. These results demonstrated the strong antiviral activity of
      SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent
      the heterosexual transmission of HIV-1. 

PMID- 24116113
TI  - Genetic features of the spontaneous self-compatible mutant, 'Jin Zhui' (Pyrus
      bretschneideri Rehd.).
AB  - 'Jin Zhui' is a spontaneous self-compatible mutant of 'Ya Li' (Pyrus
      bretschneideri Rehd. S21S34 ), the latter displaying a typical S-RNase-based
      gametophytic self-incompatibility (GSI). The pollen-part mutation (PPM) of 'Jin
      Zhui' might be due to a natural mutation in the pollen-S gene (S34 haplotype).
      However, the molecular mechanisms behind these phenotypic changes are still
      unclear. In this study, we identified five SLF (S-Locus F-box) genes in 'Ya Li',
      while no nucleotide differences were found in the SLF genes of 'Jin Zhui'.
      Further genetic analysis by S-RNase PCR-typing of selfed progeny of 'Jin Zhui'
      and 'Ya Li' * 'Jin Zhui' progeny showed three progeny classes (S21S21 , S21S34
      and S34S34 ) as opposed to the two classes reported previously (S21S34 and S34S34
      ), indicating that the pollen gametes of 'Jin Zhui', bearing either the S21 - or
      S34 -haplotype, were able to overcome self-incompatibility (SI) barriers.
      Moreover, no evidence of pollen-S duplication was found. These findings support
      the hypothesis that loss of function of S-locus unlinked PPM expressed in pollen
      leads to SI breakdown in 'Jin Zhui', rather than natural mutation in the pollen-S
      gene (S34 haplotype). Furthermore, abnormal meiosis was observed in a number of
      pollen mother cells (PMCs) in 'Jin Zhui', but not in 'Ya Li'. These and other
      interesting findings are discussed. 

PMID- 24116114
TI  - Activated effects of parathyroid hormone-related protein on human hepatic
      stellate cells.
AB  - BACKGROUND & AIMS: After years of experiments and clinical studies, parathyroid
      hormone-related protein(PTHrP) has been shown to be a bone formation promoter
      that elicits rapid effects with limited adverse reaction. Recently, PTHrP was
      reported to promote fibrosis in rat kidney in conjunction with transforming
      growth factor-beta1 (TGF-beta1), which is also a fibrosis promoter in liver.
      However, the effect of PTHrP in liver has not been determined. In this study, the
      promoting actions of PTHrP were first investigated in human normal hepatic
      stellate cells (HSC) and LX-2 cell lines. METHODS: TGF-beta1, alpha-smooth muscle
      actin (alpha-SMA), matrix metalloproteinase 2 (MMP-2), and collagen I mRNA were
      quantified by real-time polymerase chain reaction (PCR) after HSCs or LX-2 cells
      were treated with PTHrP(1-36) or TGF-beta1. Protein levels were also assessed by
      western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and
      TGF-beta1 secretion was measured with enzyme-linked immunosorbent assay (ELISA)
      of HSC cell culture media. RESULTS: In cultured human HSCs, mRNA and protein
      levels of alpha-SMA, collagen I, MMP-2, and TGF-beta1 were increased by PTHrP
      treatment. A similar increasing pattern was also observed in LX-2 cells.
      Moreover, PTHrP significantly increased TGF-beta1 secretion in cultured media
      from HSCs. CONCLUSIONS: PTHrP activated HSCs and promoted the fibrosis process in
      LX-2 cells. These procedures were probably mediated via TGF-beta1, highlighting
      the potential effects of PTHrP in the liver.

PMID- 24116115
TI  - Curcumin suppresses gelatinase B mediated norepinephrine induced stress in H9c2
      cardiomyocytes.
AB  - BACKGROUND: Extracellular matrix (ECM) remodeling facilitates biomechanical
      signals in response to abnormal physiological conditions. This process is
      witnessed as one of the major effects of the stress imposed by catecholamines,
      such as epinephrine and norepinephrine (NE), on cardiac muscle cells. Matrix
      metalloproteinases (MMPs) are the key proteases involved in degradation of the
      ECM in heart. OBJECTIVES: The present study focuses on studying the effect of
      curcumin on Gelatinase B (MMP-9), an ECM remodeling regulatory enzyme, in NE
      induced cardiac stress. Curcumin, a bioactive polyphenol found in the spice
      turmeric, has been studied for its multi-fold beneficial properties. This study
      focuses on investigating the role of curcumin as a cardio-protectant. METHODS:
      H9c2 cardiomyocytes were subjected to NE and curcumin treatments to study the
      response in stress conditions. Effect on total collagen content was studied using
      Picrosirus red staining. Gelatinase B activity was assessed through Gel-Diffusion
      Assay and Zymographic techniques. RT-PCR, Western Blotting and
      Immunocytochemistry were performed to study effect on expression of gelatinase B.
      Further, the effect of curcumin on the localization of NF-kappaB, known to
      regulate gelatinase B, was also examined. RESULTS: Curcumin suppressed the
      increase in the total collagen content under hypertrophic stress and was found to
      inhibit the in-gel and in-situ gelatinolytic activity of gelatinase B. Moreover,
      it was found to suppress the mRNA and protein expression of gelatinase B.
      CONCLUSIONS: The study provides an evidence for an overall inhibitory effect of
      curcumin on Gelatinase B in NE-induced hypertrophic stress in H9c2 cardiomyocytes
      which may contribute in the prevention of ECM remodeling.

PMID- 24116116
TI  - Characterization of novel CSF Tau and ptau biomarkers for Alzheimer's disease.
AB  - Cerebral spinal fluid (CSF) Abeta42, tau and p181tau are widely accepted
      biomarkers of Alzheimer's disease (AD). Numerous studies show that CSF tau and
      p181tau levels are elevated in mild-to-moderate AD compared to age-matched
      controls. In addition, these increases might predict preclinical AD in
      cognitively normal elderly. Despite their importance as biomarkers, the molecular
      nature of CSF tau and ptau is not known. In the current study, reverse-phase high
      performance liquid chromatography was used to enrich and concentrate tau prior to
      western-blot analysis. Multiple N-terminal and mid-domain fragments of tau were
      detected in pooled CSF with apparent sizes ranging from <20 kDa to ~40 kDa. The
      pattern of tau fragments in AD and control samples were similar. In contrast,
      full-length tau and C-terminal-containing fragments were not detected. To
      quantify levels, five tau ELISAs and three ptau ELISAs were developed to detect
      different overlapping regions of the protein. The discriminatory potential of
      each assay was determined using 20 AD and 20 age-matched control CSF samples. Of
      the tau ELISAs, the two assays specific for tau containing N-terminal sequences,
      amino acids 9-198 (numbering based on tau 441) and 9-163, exhibited the most
      significant differences between AD and control samples. In contrast, CSF tau was
      not detected with an ELISA specific for a more C-terminal region (amino acids 159
      335). Significant discrimination was also observed with ptau assays measuring
      amino acids 159-p181 and 159-p231. Interestingly, the discriminatory potential of
      p181 was reduced when measured in the context of tau species containing amino
      acids 9-p181. Taken together, these results demonstrate that tau in CSF occurs as
      a series of fragments and that discrimination of AD from control is dependent on
      the subset of tau species measured. These assays provide novel tools to
      investigate CSF tau and ptau as biomarkers for other neurodegenerative diseases. 

PMID- 24116117
TI  - Fallopian tube prolapse after hysterectomy: a systematic review.
AB  - BACKGROUND: Prolapse of the fallopian tube into the vaginal vault is a rarely
      reported complication that may occur after hysterectomy. Clinicians can miss the
      diagnosis of this disregarded complication when dealing with post-hysterectomy
      vaginal bleeding. OBJECTIVES: We performed a systematic review in order to
      describe the clinical presentation, therapeutic management and outcome of
      fallopian tube prolapse occurring after hysterectomy. SEARCH STRATEGY: A
      systematic search of MEDLINE and EMBASE references from January 1980 to December
      2010 was performed. We included articles that reported cases of fallopian tube
      prolapse after hysterectomy. Data from eligible studies were independently
      extracted onto standardized forms by two reviewers. RESULTS: Twenty-eight
      articles including 51 cases of fallopian tube prolapse after hysterectomy were
      included in this systematic review. Clinical presentations included abdominal
      pain, dyspareunia, post- coital bleeding, and/or vaginal discharge. Two cases
      were asymptomatic and diagnosed at routine checkup. The surgical management
      reported comprised partial or total salpingectomy, with vaginal repair in some
      cases combined with oophorectomy using different approaches (vaginal approach,
      combined vaginal-laparoscopic approach, laparoscopic approach, or laparotomy).
      Six patients were initially treated by silver nitrate application without
      success. CONCLUSIONS: This systematic review provided a precise summary of the
      clinical characteristics and treatment of patients presenting with fallopian tube
      prolapse following hysterectomy published in the past 30 years. We anticipate
      that these results will help inform current investigations and treatment.

PMID- 24116118
TI  - Transcriptome changes associated with anaerobic growth in Yersinia intermedia
      (ATCC29909).
AB  - BACKGROUND: The yersiniae (Enterobacteriaceae) occupy a variety of niches,
      including some in human and flea hosts. Metabolic adaptations of the yersiniae,
      which contribute to their success in these specialized environments, remain
      largely unknown. We report results of an investigation of the transcriptome under
      aerobic and anaerobic conditions for Y. intermedia, a non-pathogenic member of
      the genus that has been used as a research surrogate for Y. pestis. Y. intermedia
      shares characteristics of pathogenic yersiniae, but is not known to cause disease
      in humans. Oxygen restriction is an important environmental stimulus experienced
      by many bacteria during their life-cycles and greatly influences their survival
      in specific environments. How oxygen availability affects physiology in the
      yersiniae is of importance in their life cycles but has not been extensively
      characterized. METHODOLOGY/PRINCIPAL FINDINGS: Tiled oligonucleotide arrays based
      on a draft genome sequence of Y. intermedia were used in transcript profiling
      experiments to identify genes that change expression in response to oxygen
      availability during growth in minimal media with glucose. The expression of more
      than 400 genes, constituting about 10% of the genome, was significantly altered
      due to oxygen-limitation in early log phase under these conditions. Broad
      functional categorization indicated that, in addition to genes involved in
      central metabolism, genes involved in adaptation to stress and genes likely
      involved with host interactions were affected by oxygen-availability. Notable
      among these, were genes encoding functions for motility, chemotaxis and
      biosynthesis of cobalamin, which were up-regulated and those for iron/heme
      utilization, methionine metabolism and urease, which were down-regulated.
      CONCLUSIONS/SIGNIFICANCE: This is the first transcriptome analysis of a non
      pathogenic Yersinia spp. and one of few elucidating the global response to oxygen
      limitation for any of the yersiniae. Thus this study lays the foundation for
      further experimental characterization of oxygen-responsive genes and pathways in
      this ecologically diverse genus.

PMID- 24116119
TI  - Alterations of the transcriptome of Sulfolobus acidocaldarius by exoribonuclease
      aCPSF2.
AB  - Recent studies identified a 5' to 3' exoribonuclease termed Sso-RNase J in the
      crenarchaeon Sulfolobus solfataricus (Sso), which has been reclassified to the
      aCPSF2 (archaeal cleavage and polyadenylation specificity factor 2) group of beta
      CASP proteins. In this study, the Sso-aCPSF2 orthologue of Sulfolobus
      acidocaldarius (Saci-aCPSF2) was functionally characterized. Like Sso-aCPSF2,
      Saci-aCPSF2 degrades RNA with 5' to 3' directionality in vitro. To address the
      biological significance of Saci-aCPSF2, a deletion mutant was constructed, and
      the influence of Saci-aCPSF2 on the transcriptome profile was assessed employing
      high throughput RNA sequencing. This analysis revealed 560 genes with
      differential transcript abundance, suggesting a considerable role of this enzyme
      in RNA metabolism. In addition, bioinformatic analyses revealed several
      transcripts that are preferentially degraded at the 5' end. This was exemplarily
      verified for two transcripts by Northern-blot analyses, showing for the first
      time that aCPSF2 proteins play a role in 5' to 3' directional mRNA decay in the
      crenarchaeal clade of Archaea. 

PMID- 24116120
TI  - RNA-Seq reveals differential gene expression in Staphylococcus aureus with single
      nucleotide resolution.
AB  - Staphylococcus aureus is a gram-positive cocci and an important human commensal
      bacteria and pathogen. S. aureus infections are increasingly difficult to treat
      because of the emergence of highly resistant MRSA (methicillin-resistant S.
      aureus) strains. Here we present a method to study differential gene expression
      in S. aureus using high-throughput RNA-sequencing (RNA-seq). We used RNA-seq to
      examine gene expression in S. aureus RN4220 cells containing an exogenously
      expressed transcription factor and between two S. aureus strains (RN4220 and
      NCTC8325-4). We investigated the sequence and gene expression differences between
      RN4220 and NCTC8325-4 and used the RNA-seq data to identify S. aureus promoters
      suitable for in vitro analysis. We used RNA-seq to describe, on a genome wide
      scale, genes positively and negatively regulated by the phage encoded
      transcription factor gp67. RNA-seq offers the ability to study differential gene
      expression with single-nucleotide resolution, and is a considerable improvement
      over the predominant genome-wide transcriptome technologies used in S. aureus. 

PMID- 24116121
TI  - Inclusion of plasma lipid species improves classification of individuals at risk
      of type 2 diabetes.
AB  - BACKGROUND: A significant proportion of individuals with diabetes or impaired
      glucose tolerance have fasting plasma glucose less than 6.1 mmol/L and so are not
      identified with fasting plasma glucose measurements. In this study, we sought to
      evaluate the utility of plasma lipids to improve on fasting plasma glucose and
      other standard risk factors for the identification of type 2 diabetes or those at
      increased risk (impaired glucose tolerance). METHODS AND FINDINGS: Our diabetes
      risk classification model was trained and cross-validated on a cohort 76
      individuals with undiagnosed diabetes or impaired glucose tolerance and 170
      gender and body mass index matched individuals with normal glucose tolerance, all
      with fasting plasma glucose less than 6.1 mmol/L. The inclusion of 21 individual
      plasma lipid species to triglycerides and HbA1c as predictors in the diabetes
      risk classification model resulted in a statistically significant gain in area
      under the receiver operator characteristic curve of 0.049 (p<0.001) and a net
      reclassification improvement of 10.5% (p<0.001). The gain in area under the curve
      and net reclassification improvement were subsequently validated on a separate
      cohort of 485 subjects. CONCLUSIONS: Plasma lipid species can improve the
      performance of classification models based on standard lipid and non-lipid risk
      factors.

PMID- 24116122
TI  - Improving health worker adherence to malaria treatment guidelines in Papua New
      Guinea: feasibility and acceptability of a text message reminder service.
AB  - The aim of this study is to assess whether a text message reminder service
      designed to support health worker adherence to a revised malaria treatment
      protocol is feasible and acceptable in Papua New Guinea (PNG). The study took
      place in six purposively selected health facilities located in the Eastern
      Highlands Province (EHP) of PNG. Ten text messages designed to remind
      participants of key elements of the new NMTP were transmitted to 42 health
      workers twice over a two week period (two text messages per day, Monday to
      Friday) via the country's largest mobile network provider. The feasibility and
      acceptability of the text message reminder service was assessed by transmission
      reports, participant diaries and group discussions. Findings indicate that the
      vast majority of text messages were successfully transmitted, participants' had
      regular mobile phone access and that most text messages were read most of the
      time and were considered both acceptable and clinically useful. Nevertheless, the
      study found that PNG health workers may tire of the service if the same messages
      are repeated too many times and that health workers may be reluctant to utilize
      more comprehensive, yet complementary, resources. In conclusion, a text message
      reminder service to support health worker adherence to the new malaria treatment
      protocol is feasible and acceptable in PNG. A rigorous pragmatic, effectiveness
      trial would be justified on the basis of these findings. 

PMID- 24116123
TI  - Nevirapine-based regimens in HIV-infected antiretroviral-naive patients:
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Nevirapine belongs to the group of non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) and is commonly administered in first-line
      treatment of HIV infection. OBJECTIVE: Systematic review and meta-analysis was
      undertaken to compare effectiveness of nevirapine-based regimens with other
      antiretroviral schedules used as an initial treatment of HIV-infected
      antiretroviral-naive subjects. METHODS: Electronic databases (PubMed, EMBASE, the
      Cochrane Library, Trip Database) were searched up to 28 December 2012 for
      randomized controlled trials (RCTs) published as a full text and regarding
      nevirapine-based regimens used as a initial treatment for HIV infection. Meta
      analysis was performed with RevMan((r)) V 5.2 software. RESULTS: Twelve RCTs were
      included in the systematic review and all of them were suitable for meta
      analysis. Results of the meta-analysis have shown that nevirapine, efavirenz, and
      ritonavir-boosted protease inhibitor, added to the background regimens, were
      equally effective in terms of reaching undetectable plasma HIV RNA level as well
      as risk of disease progression or death. Compared with ritonavir-boosted protease
      inhibitor-based regimens, nevirapine-based regimens statistically significantly
      increased the risk of discontinuation of assigned treatment (RR=3.10; 95% CI:
      1.14-8.41; p<0.05). CONCLUSIONS: Despite limited RCTs data available for
      particular comparisons, our results suggest that nevirapine-based regimens may be
      considered for first-line treatment of HIV-infected adults, due to their
      comparable efficacy to the other currently recommended initial antiretroviral
      therapies.

PMID- 24116124
TI  - Expression of trefoil factor 1 in the developing and adult rat ventral
      mesencephalon.
AB  - Trefoil factor 1 (TFF1) belongs to a family of secreted peptides with a
      characteristic tree-looped trefoil structure. TFFs are mainly expressed in the
      gastrointestinal tract where they play a critical role in the function of the
      mucosal barrier. TFF1 has been suggested as a neuropeptide, but not much is known
      about its expression and function in the central nervous system. We investigated
      the expression of TFF1 in the developing and adult rat midbrain. In the adult
      ventral mesencephalon, TFF1-immunoreactive (-ir) cells were predominantly found
      in the substantia nigra pars compacta (SNc), the ventral tegmental area (VTA) and
      in periaqueductal areas. While around 90% of the TFF1-ir cells in the SNc co
      expressed tyrosine hydroxylase (TH), only a subpopulation of the TH-ir neurons
      expressed TFF1. Some TFF1-ir cells in the SNc co-expressed the calcium-binding
      proteins calbindin or calretinin and nearly all were NeuN-ir confirming a
      neuronal phenotype, which was supported by lack of co-localization with the
      astroglial marker glial fibrillary acidic protein (GFAP). Interestingly, at
      postnatal (P) day 7 and P14, a significantly higher proportion of TH-ir neurons
      in the SNc co-expressed TFF1 as compared to P21. In contrast, the proportion of
      TFF1-ir cells expressing TH remained unchanged during postnatal development.
      Furthermore, significantly more TH-ir neurons expressed TFF1 in the SNc, compared
      to the VTA at all four time-points investigated. Injection of the tracer
      fluorogold into the striatum of adult rats resulted in retrograde labeling of
      several TFF1 expressing cells in the SNc showing that a significant fraction of
      the TFF1-ir cells were projection neurons. This was also reflected by unilateral
      loss of TFF1-ir cells in SNc of 6-hydroxylase-lesioned hemiparkinsonian rats. In
      conclusion, we show for the first time that distinct subpopulations of midbrain
      dopaminergic neurons express TFF1, and that this expression pattern is altered in
      a rat model of Parkinson's disease. 

PMID- 24116125
TI  - Structural analysis of intermolecular interactions in the kinesin adaptor complex
      fasciculation and elongation protein zeta 1/ short coiled-coil protein
      (FEZ1/SCOCO).
AB  - Cytoskeleton and protein trafficking processes, including vesicle transport to
      synapses, are key processes in neuronal differentiation and axon outgrowth. The
      human protein FEZ1 (fasciculation and elongation protein zeta 1 / UNC-76, in C.
      elegans), SCOCO (short coiled-coil protein / UNC-69) and kinesins (e.g. kinesin
      heavy chain / UNC116) are involved in these processes. Exploiting the feature of
      FEZ1 protein as a bivalent adapter of transport mediated by kinesins and FEZ1
      protein interaction with SCOCO (proteins involved in the same path of axonal
      growth), we investigated the structural aspects of intermolecular interactions
      involved in this complex formation by NMR (Nuclear Magnetic Resonance), cross
      linking coupled with mass spectrometry (MS), SAXS (Small Angle X-ray Scattering)
      and molecular modelling. The topology of homodimerization was accessed through
      NMR (Nuclear Magnetic Resonance) studies of the region involved in this process,
      corresponding to FEZ1 (92-194). Through studies involving the protein in its
      monomeric configuration (reduced) and dimeric state, we propose that
      homodimerization occurs with FEZ1 chains oriented in an anti-parallel topology.
      We demonstrate that the interaction interface of FEZ1 and SCOCO defined by MS and
      computational modelling is in accordance with that previously demonstrated for
      UNC-76 and UNC-69. SAXS and literature data support a heterotetrameric complex
      model. These data provide details about the interaction interfaces probably
      involved in the transport machinery assembly and open perspectives to understand
      and interfere in this assembly and its involvement in neuronal differentiation
      and axon outgrowth. 

PMID- 24116126
TI  - Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a
      combination analysis.
AB  - Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a
      non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent
      pain, however with moderate gastrointestinal side effects or analgesia tolerance.
      One promising analgesic strategy is to give a combined prescription, allowing the
      maximal or equal efficacy with fewer side effects. In the current study, the
      efficacy and side effects of combined administration of duloxetine and celecoxib
      were tested in the mouse formalin pain model. The subcutaneous (s.c.) injection
      of formalin into the left hindpaw induced significant somatic and emotional pain
      evaluated by the biphasic spontaneous flinching of the injected hindpaw and
      interphase ultrasonic vocalizations (USVs) during the 1 h after formalin
      injection, respectively. Pretreatment with intraperitoneal (i.p.) injection of
      duloxetine or celecoxib at 1 h before formalin injection induced the dose
      dependent inhibition on the second but not first phase pain responses. Combined
      administration of duloxetine and celecoxib showed significant analgesia for the
      second phase pain responses. Combination analgesia on the first phase was
      observed only with higher dose combination. A statistical difference between the
      theoretical and experimental ED50 for the second phase pain responses was
      observed, which indicated synergistic interaction of the two drugs. Concerning
      the emotional pain responses revealed with USVs, we assumed that the
      antinociceptive effects were almost completely derived from duloxetine, since
      celecoxib was ineffective when administered alone or reduced the dosage of
      duloxetine when given in combination. Based on the above findings, acute
      concomitant administration of duloxetine and celecoxib showed synergism on the
      somatic pain behavior but not emotional pain behaviors. 

PMID- 24116127
TI  - An MRI-visible non-viral vector bearing GD2 single chain antibody for targeted
      gene delivery to human bone marrow mesenchymal stem cells.
AB  - The neural ganglioside GD2 has recently been reported to be a novel surface
      marker that is only expressed on human bone marrow mesenchymal stem cells within
      normal marrow. In this study, an MRI-visible, targeted, non-viral vector for
      effective gene delivery to human bone marrow mesenchymal stem cells was first
      synthesized by attaching a targeting ligand, the GD2 single chain antibody
      (scAbGD2), to the distal ends of PEG-g-PEI-SPION. The targeted vector was then
      used to condense plasmid DNA to form nanoparticles showing stable small size, low
      cytotoxicity, and good biocompatibility. Based on a reporter gene assay, the
      transfection efficiency of targeting complex reached the highest value at 59.6%
      +/- 4.5% in human bone marrow mesenchymal stem cells, which was higher than those
      obtained using nontargeting complex and lipofectamine/pDNA (17.7% +/- 2.9% and
      34.9% +/- 3.6%, respectively) (P<0.01). Consequently, compared with the
      nontargeting group, more in vivo gene expression was observed in the fibrotic rat
      livers of the targeting group. Furthermore, the targeting capacity of scAbGD2-PEG
      g-PEI-SPION was successfully verified in vitro by confocal laser scanning
      microscopy, Prussian blue staining, and magnetic resonance imaging. Our results
      indicate that scAbGD2-PEG-g-PEI-SPION is a promising MRI-visible non-viral vector
      for targeted gene delivery to human bone marrow mesenchymal stem cells. 

PMID- 24116128
TI  - Lack of association between stroke and left atrial out-pouching structures:
      results of a case-control study.
AB  - BACKGROUND AND PURPOSE: Clinical significance of out-pouching structures of the
      left atrium (LA) as potential embolic sources remains unclear. We sought to
      evaluate the association between stroke and LA out-pouching structures. METHODS:
      A case-control study was conducted to assess the prevalence of LA out-pouching
      structures in subjects with and without stroke. Case subjects were 270 stroke
      patients who had undergone cardiac CT. Control subjects were 270 age- and sex
      matched patients without a history of stroke and who had undergone cardiac CT.
      Presence of LA out-pouching structures was determined by ECG-gated cardiac CT.
      The location of out-pouching structures was categorized as near Bachmann bundle,
      anterior, inferoseptal, inferior, and lateral. The prevalence, number and
      location of out-pouching structures and clinical characteristics were compared
      between the two groups. RESULTS: One hundred sixty eight out-pouching structures
      were identified in 139 stroke patients (51%), while a total of 169 out-pouching
      structures were found in 155 control patients (57%) (p=0.1949). The prevalence of
      LA out-pouching structures with different locations was not significantly
      different between the stroke group and control group. In the stroke group, the
      prevalence of out-pouching structures was not significantly different by subtypes
      of ischemic stroke and the prevalence of LA out-pouching structures was not
      different between patients with atrial fibrillation (AF) and without AF.
      CONCLUSION: The left atrial out-pouching structures are commonly seen in a
      population with and without stroke with similar prevalence. Our study suggests
      that LA out-pouching structures are not significant risk factors of stroke.

PMID- 24116129
TI  - Evolutionary insight into the functional amyloids of the pseudomonads.
AB  - Functional bacterial amyloids (FuBA) are important components in many
      environmental biofilms where they provide structural integrity to the biofilm,
      mediate bacterial aggregation and may function as virulence factor by binding
      specifically to host cell molecules. A novel FuBA system, the Fap system, was
      previously characterized in the genus Pseudomonas, however, very little is known
      about the phylogenetic diversity of bacteria with the genetic capacity to apply
      this system. Studies of genomes and public metagenomes from a diverse range of
      habitats showed that the Fap system is restricted to only three classes in the
      phylum Proteobacteria, the Beta-, Gamma- and Deltaproteobacteria. The structural
      organization of the fap genes into a single fapABCDEF operon is well conserved
      with minor variations such as a frequent deletion of fapA. A high degree of
      variation was seen within the primary structure of the major Fap fibril monomers,
      FapC, whereas the minor monomers, FapB, showed less sequence variation.
      Comparison of phylogenetic trees based on Fap proteins and the 16S rRNA gene of
      the corresponding bacteria showed remarkably similar overall topology. This
      indicates, that horizontal gene transfer is an infrequent event in the evolution
      of the Fap system. 

PMID- 24116130
TI  - Partially penetrant postnatal lethality of an epithelial specific MicroRNA in a
      mouse knockout.
AB  - MicroRNAs are small noncoding RNAs thought to have pivotal roles in numerous
      diseases and developmental processes. However, a growing body of literature
      indicates that in vivo elimination of these tiny RNAs usually has little to no
      observable consequence, suggesting functional redundancy with other microRNAs or
      cellular pathways. We provide an in-depth analysis of miR-205 expression and
      define miR-205 as an epithelial-specific microRNA, and for the first time show
      that ablation of this microRNA knockout exhibits partially penetrant lethality in
      a constitutive mouse knockout model. Given the role of this microRNA in cancer
      and development, this mouse model will be an incredible reagent to study the
      function and mechanisms of miR-205 in epithelial tissue development and disease. 

PMID- 24116131
TI  - Comparison of cellular and transcriptional responses to 1,25-dihydroxyvitamin d3
      and glucocorticoids in peripheral blood mononuclear cells.
AB  - Glucocorticoids (GC) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are steroid
      hormones with anti-inflammatory properties with enhanced effects when combined.
      We previously showed that transcriptional response to GCs was correlated with
      inter-individual and inter-ethnic cellular response. Here, we profiled cellular
      and transcriptional responses to 1,25(OH)2 D3 from the same donors. We studied
      cellular response to combined treatment with GCs and 1,25(OH)2 D3 in a subset of
      individuals least responsive to GCs. We found that combination treatment had
      significantly greater inhibition of proliferation than with either steroid
      hormone alone. Overlapping differentially expressed (DE) genes between the two
      hormones were enriched for adaptive and innate immune processes. Non-overlapping
      differentially expressed genes with 1,25(OH)2 D3 treatment were enriched for
      pathways involving the electron transport chain, while with GC treatment, non
      overlapping genes were enriched for RNA-related processes. These results suggest
      that 1,25(OH)2 D3 enhances GC anti-inflammatory properties through a number of
      shared and non-shared transcriptionally-mediated pathways. 

PMID- 24116132
TI  - Acceptability of pre-exposure prophylaxis among men who have sex with men and
      transgender women in Northern Thailand.
AB  - BACKGROUND: Northern Thailand has a high burden HIV epidemic among MSM and TG.
      Oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine has
      demonstrated efficacy in preventing HIV among MSM and TG in Chiang Mai, Thailand.
      Determinants of PrEP acceptability are needed to gauge the potential uptake of
      this prevention strategy. METHODS: From January to February 2012, 238 MSM and TG
      participants, who self-reported as HIV-uninfected or of unknown status, completed
      a self-administered survey on hand-held computers. Participants were recruited by
      venue-day-time sampling and asked to rate their likelihood of using oral PrEP for
      HIV prevention with an efficacy of 50%. PrEP acceptability was defined as being
      "very likely" to use PrEP. Odds ratios and 95% CIs were calculated to identify
      correlates of acceptability. RESULTS: 131 MSM and 107 TG responded, with mean
      ages of 23.7 and 21.8, respectively. 24% of MSM engaged primarily in receptive
      anal sex vs. 74% of TG. 21% of MSM and 44% of TG reported regular medication use.
      Prior awareness of PrEP was high at 66% among both MSM and TG respondents. 41% of
      MSM and 37% of TG were "very likely" to use PrEP. Among MSM, factors associated
      with PrEP acceptability included a prior history of STIs (AOR 4.6; 95%CIs 1.7
      12.6), previous HIV testing (AOR 2.4 95%CIs 1.1-5.3), regularly planned sex (AOR
      2.8 95%CIs 1.1-7.2), and infrequent sex (AOR 2.9 95%CIs 1.3-6.3). Among TG,
      factors associated with acceptability included prior awareness of PrEP (AOR 3.3;
      95%CIs 1.2-9.0) and having private insurance (AOR 5.0; 95%CIs 1.3-19.0).
      CONCLUSION: MSM and TG in Northern Thailand are distinct groups in terms of
      sexual behaviors, patterns of medication use, and correlates of PrEP
      acceptability. Efforts to maximize PrEP uptake should include expanded HIV
      testing services and the provision of financial subsidies to reduce the cost of
      PrEP.

PMID- 24116133
TI  - The interactive effects of pulsed grazing disturbance and patch size vary among
      wetland arthropod guilds.
AB  - Pulse disturbances and habitat patch size can determine community composition
      independently or in concert, and may be particularly influential on small spatial
      scales for organisms with low mobility. In a field experiment, we investigated
      whether the effects of a pulsed disturbance that simulated a grazing event varied
      with habitat patch size. We focused on the short-term responses of multiple co
      occurring emergent salt marsh arthropods with differing levels of mobility and
      dispersal potential. As part of a marsh restoration project, two types of
      emergent marsh structures were created: small circular mounds (0.5 m diameter)
      separated by several meters of aquatic habitat, and larger, elongated terraces
      (>50 m long). Study plots (0.25 m(2)) were established on both structures; in a
      subset of plots, we simulated a pulsed grazing disturbance event by clipping the
      aboveground tissue of emergent plants, primarily Spartina alterniflora. At the
      end of the two-month recovery period, Ischnodemus (Hemiptera: Blissidae) density
      was over 50% lower in disturbed treatments within both large (terrace) and small
      (mound) patches. Predatory spider treatment responses were similar to Ischnodemus
      responses, suggesting a trophic relationship between those two arthropod groups.
      Alternatively, spiders may have been directly affected by the loss of shelter in
      the disturbed plots. Prokelisia (Homoptera: Delphacidae), which are generally
      more mobile than Ischnodemus, were not affected by disturbance treatment or by
      patch size, suggesting the potential for rapid recolonization following
      disturbance. Larval stem borers decreased by an order of magnitude in disturbed
      plots, but only in the large patches. In general, the disturbance effects of
      vegetation removal on arthropod density and community composition were stronger
      than patch size effects, and there were few interactions between pulsed
      disturbance and patch size. Rather, emergent marsh arthropod responses to
      disturbance and habitat area treatments were linked to the dispersal potential
      and mobility of each individual taxon. 

PMID- 24116134
TI  - Role of key salt bridges in thermostability of G. thermodenitrificans EstGtA2:
      distinctive patterns within the new bacterial lipolytic enzyme subfamily XIII.2
      [corrected].
AB  - Bacterial lipolytic enzymes were originally classified into eight different
      families defined by Arpigny and Jaeger (families I-VIII). Recently, the discovery
      of new lipolytic enzymes allowed for extending the original classification to
      fourteen families (I-XIV). We previously reported that G. thermodenitrificans
      EstGtA2 (access no. AEN92268) belonged to a novel group of bacterial lipolytic
      enzymes. Here we propose a 15(th) family (family XV) and suggest criteria for the
      assignation of protein sequences to the N' subfamily. Five selected salt bridges,
      hallmarks of the N' subfamily (E3/R54, E12/R37, E66/R140, D124/K178 and
      D205/R220) were disrupted in EstGtA2 using a combinatorial alanine-scanning
      approach. A set of 14 (R/K->A) mutants was produced, including five single, three
      double, three triple and three quadruple mutants. Despite a high tolerance to non
      conservative mutations for folding, all the alanine substitutions were
      destabilizing (decreasing T m by 5 to 14 degrees C). A particular combination of
      four substitutions exceeded this tolerance and prevents the correct folding of
      EstGtA2, leading to enzyme inactivation. Although other mutants remain active at
      low temperatures, the accumulation of more than two mutations had a dramatic
      impact on EstGtA2 activity at high temperatures suggesting an important role of
      these conserved salt bridge-forming residues in thermostability of lipolytic
      enzymes from the N' subfamily. We also identified a particular interloop salt
      bridge in EstGtA2 (D194/H222), located at position i -2 and i -4 residues from
      the catalytic Asp and His respectively which is conserved in other related
      bacterial lipolytic enzymes (families IV and XIII) with high tolerance to
      mutations and charge reversal. We investigated the role of residue identity at
      position 222 in controlling stability-pH dependence in EstGtA2. The introduction
      of a His to Arg mutation led to increase thermostability under alkaline pH. Our
      results suggest primary targets for optimization of EstGtA2 for specific
      biotechnological purposes. 

PMID- 24116135
TI  - Catalytic inhibitors of topoisomerase II differently modulate the toxicity of
      anthracyclines in cardiac and cancer cells.
AB  - Anthracyclines (such as doxorubicin or daunorubicin) are among the most effective
      anticancer drugs, but their usefulness is hampered by the risk of irreversible
      cardiotoxicity. Dexrazoxane (ICRF-187) is the only clinically approved
      cardioprotective agent against anthracycline cardiotoxicity. Its activity has
      traditionally been attributed to the iron-chelating effects of its metabolite
      with subsequent protection from oxidative stress. However, dexrazoxane is also a
      catalytic inhibitor of topoisomerase II (TOP2). Therefore, we examined whether
      dexrazoxane and two other TOP2 catalytic inhibitors, namely sobuzoxane (MST-16)
      and merbarone, protect cardiomyocytes from anthracycline toxicity and assessed
      their effects on anthracycline antineoplastic efficacy. Dexrazoxane and two other
      TOP2 inhibitors protected isolated neonatal rat cardiomyocytes against toxicity
      induced by both doxorubicin and daunorubicin. However, none of the TOP2
      inhibitors significantly protected cardiomyocytes in a model of hydrogen peroxide
      induced oxidative injury. In contrast, the catalytic inhibitors did not
      compromise the antiproliferative effects of the anthracyclines in the HL-60
      leukemic cell line; instead, synergistic interactions were mostly observed.
      Additionally, anthracycline-induced caspase activation was differentially
      modulated by the TOP2 inhibitors in cardiac and cancer cells. Whereas dexrazoxane
      was upon hydrolysis able to significantly chelate intracellular labile iron ions,
      no such effect was noted for either sobuzoxane or merbarone. In conclusion, our
      data indicate that dexrazoxane may protect cardiomyocytes via its catalytic TOP2
      inhibitory activity rather than iron-chelation activity. The differential
      expression and/or regulation of TOP2 isoforms in cardiac and cancer cells by
      catalytic inhibitors may be responsible for the selective modulation of
      anthracycline action observed. 

PMID- 24116136
TI  - Microcirculatory rarefaction in South Asians - a potential mechanism for
      increased cardiovascular risk and diabetes.
AB  - People of South Asian descent have an increased risk of cardiovascular disease
      (CVD) and diabetes, but little is known about the microcirculation in South Asian
      people despite evidence that this plays an important role in the aetiology of
      CVD. We compared the retinal microcirculation in a population-based sample of 287
      middle-aged adults (144 European 143 South Asian) matched for age and sex.
      Retinal photographs were taken and analysed using a validated semi-automated
      program and microvascular measures were compared. Blood pressure, anthropometry
      and fasting bloods were also measured. South Asians had significantly fewer
      arteriolar and venular vessels and bifurcations. Arterioles and venules were
      longer and venules were also more tortuous in South Asians. These differences
      were not explained by adjustment for traditional risk factors including blood
      pressure, body mass index, diabetes or measures of insulin resistance. People of
      South Asian descent have rarefaction of the retinal microcirculation compared to
      age-sex matched individuals of European descent. Reduced microvascular density
      could contribute to the elevated risk of CVD and impaired glucose tolerance in
      South Asian people. 

PMID- 24116137
TI  - Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co
      determines the prognosis of colon cancer patients.
AB  - Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto
      oncogene that is linked to the development and progression of several cancers. In
      this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor
      adjacent mucosa together as an independent prognostic factor for colon cancer
      patients. The study included 343 colon cancer patients. Immunohistochemical
      staining was used to detect pim-1. Multivariate cox regression for disease-free
      survival (DFS) were used to identify independent prognostic factors. Analytic
      hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors,
      tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score
      (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for
      patients with different pim-1 expression levels were compared using the log-rank
      test. In this study, four independent prognostic factors were identified for
      colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent
      mucosa, as well as tumor stage. It has been established that clinical stage is an
      important prognostic factor for colon cancer patients. However, PTS can identify
      the patients who are likely to recur not only in the whole radical excision group
      but also within each stage of this group. Based on the results of this study we
      can conclude that the PTS combined with clinical staging system may be a better
      predictor of colon cancer patients' prognosis than using the clinical stage
      system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

PMID- 24116138
TI  - The Sequencing Bead Array (SBA), a next-generation digital suspension array.
AB  - Here we describe the novel Sequencing Bead Array (SBA), a complete assay for
      molecular diagnostics and typing applications. SBA is a digital suspension array
      using Next-Generation Sequencing (NGS), to replace conventional optical readout
      platforms. The technology allows for reducing the number of instruments required
      in a laboratory setting, where the same NGS instrument could be employed from
      whole-genome and targeted sequencing to SBA broad-range biomarker detection and
      genotyping. As proof-of-concept, a model assay was designed that could
      distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical
      cancer progression. SBA was used to genotype 20 cervical tumor samples and, when
      compared with amplicon pyrosequencing, was able to detect two additional co
      infections due to increased sensitivity. We also introduce in-house software
      Sphix, enabling easy accessibility and interpretation of results. The technology
      offers a multi-parallel, rapid, robust, and scalable system that is readily
      adaptable for a multitude of microarray diagnostic and typing applications, e.g.
      genetic signatures, single nucleotide polymorphisms (SNPs), structural
      variations, and immunoassays. SBA has the potential to dramatically change the
      way we perform probe-based applications, and allow for a smooth transition
      towards the technology offered by genomic sequencing. 

PMID- 24116139
TI  - A remote palm domain residue of RB69 DNA polymerase is critical for enzyme
      activity and influences the conformation of the active site.
AB  - Non-conserved amino acids that are far removed from the active site can sometimes
      have an unexpected effect on enzyme catalysis. We have investigated the effects
      of alanine replacement of residues distant from the active site of the
      replicative RB69 DNA polymerase, and identified a substitution in a weakly
      conserved palm residue (D714A), that renders the enzyme incapable of sustaining
      phage replication in vivo. D714, located several angstroms away from the active
      site, does not contact the DNA or the incoming dNTP, and our apoenzyme and
      ternary crystal structures of the Pol(D714A) mutant demonstrate that D714A does
      not affect the overall structure of the protein. The structures reveal a
      conformational change of several amino acid side chains, which cascade out from
      the site of the substitution towards the catalytic center, substantially
      perturbing the geometry of the active site. Consistent with these structural
      observations, the mutant has a significantly reduced k pol for correct
      incorporation. We propose that the observed structural changes underlie the
      severe polymerization defect and thus D714 is a remote, non-catalytic residue
      that is nevertheless critical for maintaining an optimal active site
      conformation. This represents a striking example of an action-at-a-distance
      interaction. 

PMID- 24116140
TI  - Effect of change in spindle structure on proliferation inhibition of osteosarcoma
      cells and osteoblast under simulated microgravity during incubation in rotating
      bioreactor.
AB  - In order to study the effect of microgravity on the proliferation of mammalian
      osteosarcoma cells and osteoblasts, the changes in cell proliferation, spindle
      structure, expression of MAD2 or BUB1, and effect of MAD2 or BUB1 on the
      inhibition of cell proliferation is investigated by keeping mammalian
      osteosarcoma cells and osteoblasts under simulated microgravity in a rotating
      wall vessel (2D-RWVS) bioreactor. Experimental results indicate that the effect
      of microgravity on proliferation inhibition, incidence of multipolar spindles,
      and expression of MAD2 or BUB1 increases with the extension of treatment time.
      And multipolar cells enter mitosis after MAD2 or BUB1 is knocked down, which
      leads to the decrease in DNA content, and decrease the accumulation of cells
      within multipolar spindles. It can therefore be concluded that simulated
      microgravity can alter the structure of spindle microtubules, and stimulate the
      formation of multipolar spindles together with multicentrosomes, which causes the
      overexpression of SAC proteins to block the abnormal cells in metaphase, thereby
      inhibiting cell proliferation. By clarifying the relationship between cell
      proliferation inhibition, spindle structure and SAC changes under simulated
      microgravity, the molecular mechanism and morphology basis of proliferation
      inhibition induced by microgravity is revealed, which will give experiment and
      theoretical evidence for the mechanism of space bone loss and some other space
      medicine problems. 

PMID- 24116141
TI  - Ulmus davidiana var. japonica Nakai upregulates eosinophils and suppresses Th1
      and Th17 cells in the small intestine.
AB  - The bark of Ulmus davidiana var. japonica Nakai (Ulmaceae) has been used in
      traditional Korean medicine for chronic inflammation in the gastrointestinal
      tract. Here we investigated the frequency and cytokine profile of the major
      immune cells in the small intestinal lamina propria (SI LP), spleen, and
      mesenteric lymph nodes (MLNs) of mice treated orally with Ulmus davidiana var.
      japonica Nakai bark water extract (UDE) to address the immunomodulatory role of
      this herb in intestinal homeostasis. B6 mice were given 5g/kg UDE once daily for
      14 days. They were then sacrificed, and cells were isolated from the spleen,
      MLNs, and SI LP. The proportion of B versus T lymphocytes, CD4(+) versus CD8(+) T
      lymphocytes, Th1 and Th17 cells, and Foxp3(+) regulatory T cells in the spleen,
      MLNs, and SI LP were analyzed. The frequency of antigen-presenting cells (APCs),
      including dendritic cells, macrophages, and eosinophils in the SI LP and the
      expression of costimulatory molecules on APCs were also evaluated. The numbers
      and frequencies of Th1 and Th17 cells in the SI LP were significantly reduced in
      the UDE-treated mice compared with PBS controls. In addition, the proportion of
      IL-4-producing eosinophils in the SI LP was significantly elevated in the UDE
      treated mice compared with controls. Taken together, these data indicate that UDE
      up-regulates the number and frequency of SI LP eosinophils, which can down
      regulate the Th1 and Th17 responses via IL-4 secretion and contribute to
      intestinal homeostasis. 

PMID- 24116142
TI  - Permeability transition pore-mediated mitochondrial superoxide flashes regulate
      cortical neural progenitor differentiation.
AB  - In the process of neurogenesis, neural progenitor cells (NPCs) cease dividing and
      differentiate into postmitotic neurons that grow dendrites and an axon, become
      excitable, and establish synapses with other neurons. Mitochondrial biogenesis
      and aerobic metabolism provide energy substrates required to support the
      differentiation, growth and synaptic activity of neurons. Mitochondria may also
      serve signaling functions and, in this regard, it was recently reported that
      mitochondria can generate rapid bursts of superoxide (superoxide flashes), the
      frequency of which changes in response to environmental conditions and signals
      including oxygen levels and Ca(2+) fluxes. Here we show that the frequency of
      mitochondrial superoxide flashes increases as embryonic cerebral cortical neurons
      differentiate from NPCs, and provide evidence that the superoxide flashes serve a
      signaling function that is critical for the differentiation process. The
      superoxide flashes are mediated by mitochondrial permeability transition pore
      (mPTP) opening, and pharmacological inhibition of the mPTP suppresses neuronal
      differentiation. Moreover, superoxide flashes and neuronal differentiation are
      inhibited by scavenging of mitochondrial superoxide. Conversely, manipulations
      that increase superoxide flash frequency accelerate neuronal differentiation. Our
      findings reveal a regulatory role for mitochondrial superoxide flashes, mediated
      by mPTP opening, in neuronal differentiation. 

PMID- 24116143
TI  - Identification, characterization, and functional analysis of Tube and Pelle
      homologs in the mud crab Scylla paramamosain.
AB  - Tube and Pelle are essential components in Drosophila Toll signaling pathway. In
      this study, we characterized a pair of crustacean homologs of Tube and Pelle in
      Scylla paramamosain, namely, SpTube and SpPelle, and analyzed their immune
      functions. The full-length cDNA of SpTube had 2052 bp with a 1578 bp open reading
      frame (ORF) encoding a protein with 525 aa. A death domain (DD) and a kinase
      domain were predicted in the deduced protein. The full-length cDNA of SpPelle had
      3825 bp with a 3420 bp ORF encoding a protein with 1140 aa. The protein contained
      a DD and a kinase domain. Two conserved repeat motifs previously called Tube
      repeat motifs present only in insect Tube or Tube-like sequences were found
      between these two domains. Alignments and structure predictions demonstrated that
      SpTubeDD and SpPelleDD significantly differed in sequence and 3D structure.
      Similar to TubeDD, SpTubeDD contained three common conserved residues (R, K, and
      R) on one surface that may mediate SpMyD88 binding and two common residues (A and
      A) on the other surface that may contribute to Pelle binding. By contrast,
      SpPelleDD lacked similar conservative residues. SpTube, insect Tube-like kinases,
      and human IRAK4 were found to be RD kinases with an RD dipeptide in the kinase
      domain. SpPelle, Pelle, insect Pelle-like kinases, and human IRAK1 were found to
      be non-RD kinases lacking an RD dipeptide. Both SpTube and SpPelle were highly
      expressed in hemocytes, gills, and hepatopancreas. Upon challenge, SpTube and
      SpPele were significantly increased in hemocytes by Gram-negative or Gram
      positive bacteria, whereas only SpPelle was elevated by White Spot Syndrome
      Virus. The pull-down assay showed that SpTube can bind to both SpMyD88 and
      SpPelle. These results suggest that SpTube, SpPelle, and SpMyD88 may form a
      trimeric complex involved in the immunity of mud crabs against both Gram-negative
      and Gram-positive bacteria. 

PMID- 24116144
TI  - Conditional gene expression in Chlamydia trachomatis using the tet system.
AB  - Chlamydia trachomatis is maintained through a complex bi-phasic developmental
      cycle that incorporates numerous processes that are poorly understood. This is
      reflective of the previous paucity of genetic tools available. The recent advent
      of a method for transforming Chlamydia has enabled the development of essential
      molecular tools to better study these medically important bacteria. Critical for
      the study of Chlamydia biology and pathogenesis, is a system for tightly
      controlled inducible gene expression. To accomplish this, a new shuttle vector
      was generated with gene expression controlled by the Tetracycline repressor and
      anhydryotetracycline. Evaluation of GFP expression by this system demonstrated
      tightly controlled gene regulation with rapid protein expression upon induction
      and restoration of transcription repression following inducer removal.
      Additionally, induction of expression could be detected relatively early during
      the developmental cycle and concomitant with conversion into the metabolically
      active form of Chlamydia. Uniform and strong GFP induction was observed during
      middle stages of the developmental cycle. Interestingly, variable induced GFP
      expression by individual organisms within shared inclusions during later stages
      of development suggesting metabolic diversity is affecting induction and/or
      expression. These observations support the strong potential of this molecular
      tool to enable numerous experimental analyses for a better understanding of the
      biology and pathogenesis of Chlamydia. 

PMID- 24116145
TI  - Myosin XIK of Arabidopsis thaliana accumulates at the root hair tip and is
      required for fast root hair growth.
AB  - Myosin motor proteins are thought to carry out important functions in the
      establishment and maintenance of cell polarity by moving cellular components such
      as organelles, vesicles, or protein complexes along the actin cytoskeleton. In
      Arabidopsis thaliana, disruption of the myosin XIK gene leads to reduced
      elongation of the highly polar root hairs, suggesting that the encoded motor
      protein is involved in this cell growth. Detailed live-cell observations in this
      study revealed that xik root hairs elongated more slowly and stopped growth
      sooner than those in wild type. Overall cellular organization including the actin
      cytoskeleton appeared normal, but actin filament dynamics were reduced in the
      mutant. Accumulation of RabA4b-containing vesicles, on the other hand, was not
      significantly different from wild type. A functional YFP-XIK fusion protein that
      could complement the mutant phenotype accumulated at the tip of growing root
      hairs in an actin-dependent manner. The distribution of YFP-XIK at the tip,
      however, did not match that of the ER or several tip-enriched markers including
      CFP-RabA4b. We conclude that the myosin XIK is required for normal actin dynamics
      and plays a role in the subapical region of growing root hairs to facilitate
      optimal growth. 

PMID- 24116146
TI  - Meta-analysis identifies NF-kappaB as a therapeutic target in renal cancer.
AB  - OBJECTIVE: To determine the expression patterns of NF-kappaB regulators and
      target genes in clear cell renal cell carcinoma (ccRCC), their correlation with
      von Hippel Lindau (VHL) mutational status, and their association with survival
      outcomes. METHODS: Meta-analyses were carried out on published ccRCC gene
      expression datasets by RankProd, a non-parametric statistical method. DEGs with a
      False Discovery Rate of < 0.05 by this method were considered significant, and
      intersected with a curated list of NF-kappaB regulators and targets to determine
      the nature and extent of NF-kappaB deregulation in ccRCC. RESULTS: A highly
      disproportionate fraction (~40%; p < 0.001) of NF-kappaB regulators and target
      genes were found to be up-regulated in ccRCC, indicative of elevated NF-kappaB
      activity in this cancer. A subset of these genes, comprising a key NF-kappaB
      regulator (IKBKB) and established mediators of the NF-kappaB cell-survival and
      pro-inflammatory responses (MMP9, PSMB9, and SOD2), correlated with higher
      relative risk, poorer prognosis, and reduced overall patient survival.
      Surprisingly, levels of several interferon regulatory factors (IRFs) and
      interferon target genes were also elevated in ccRCC, indicating that an
      'interferon signature' may represent a novel feature of this disease. Loss of VHL
      gene expression correlated strongly with the appearance of NF-kappaB- and
      interferon gene signatures in both familial and sporadic cases of ccRCC. As NF
      kappaB controls expression of key interferon signaling nodes, our results suggest
      a causal link between VHL loss, elevated NF-kappaB activity, and the appearance
      of an interferon signature during ccRCC tumorigenesis. CONCLUSIONS: These
      findings identify NF-kappaB and interferon signatures as clinical features of
      ccRCC, provide strong rationale for the incorporation of NF-kappaB inhibitors
      and/or and the exploitation of interferon signaling in the treatment of ccRCC,
      and supply new NF-kappaB targets for potential therapeutic intervention in this
      currently-incurable malignancy.

PMID- 24116147
TI  - Mutation in the kv3.3 voltage-gated potassium channel causing spinocerebellar
      ataxia 13 disrupts sound-localization mechanisms.
AB  - Normal sound localization requires precise comparisons of sound timing and
      pressure levels between the two ears. The primary localization cues are
      interaural time differences, ITD, and interaural level differences, ILD. Voltage
      gated potassium channels, including Kv3.3, are highly expressed in the auditory
      brainstem and are thought to underlie the exquisite temporal precision and rapid
      spike rates that characterize brainstem binaural pathways. An autosomal dominant
      mutation in the gene encoding Kv3.3 has been demonstrated in a large Filipino
      kindred manifesting as spinocerebellar ataxia type 13 (SCA13). This kindred
      provides a rare opportunity to test in vivo the importance of a specific channel
      subunit for human hearing. Here, we demonstrate psychophysically that individuals
      with the mutant allele exhibit profound deficits in both ITD and ILD sensitivity,
      despite showing no obvious impairment in pure-tone sensitivity with either ear.
      Surprisingly, several individuals exhibited the auditory deficits even though
      they were pre-symptomatic for SCA13. We would expect that impairments of binaural
      processing as great as those observed in this family would result in prominent
      deficits in localization of sound sources and in loss of the "spatial release
      from masking" that aids in understanding speech in the presence of competing
      sounds. 

PMID- 24116148
TI  - Polyenylpyrrole derivatives inhibit NLRP3 inflammasome activation and
      inflammatory mediator expression by reducing reactive oxygen species production
      and mitogen-activated protein kinase activation.
AB  - Two polyenylpyrroles from a soil ascomycete Gymnoascus reessii were previously
      identified as hit compounds in screening for cytotoxicity against lung cancer
      cells. These compounds and various analogs, which have been previously
      synthesized and tested for anti-lung cancer cell activity, were tested for anti
      inflammatory activity. After preliminary screening for cytotoxicity for RAW 264.7
      murine macrophage cells, the non-toxic compounds were tested for anti
      inflammatory activity using lipopolysaccharide (LPS)-activated RAW 264.7 cells.
      Compounds 1h, 1i, and 1n reduced LPS-induced nitric oxide (NO) production, with
      respective ED50 values of 15 +/- 2, 16 +/- 2, and 17 +/- 2 uM. They also reduced
      expression of inducible NO synthase and interleukin-6 (IL-6) without affecting
      cyclooxygenase-2 expression. Compound 1h also reduced secretion of IL-6 and tumor
      necrosis factor-alpha by LPS-activated J774A.1 murine macrophage cells, primary
      mice peritoneal macrophages, and JAWSII murine bone marrow-derived dendritic
      cells and reduced NLRP3 inflammasome-mediated interleukin-1beta (IL-1beta)
      secretion by LPS + adenosine triphosphate-activated J774A.1 and JAWSII cells. The
      underlying mechanisms for the anti-inflammatory activity of compound 1h were
      found to be a decrease in LPS-induced reactive oxygen species (ROS) production,
      mitogen-activated protein kinase phosphorylation, and NF-kappaB activation and a
      decrease in ATP-induced ROS production and PKC-alpha phosphorylation. These
      results provide promising insights into the anti-inflammatory activity of these
      conjugated polyenes and a molecular rationale for future therapeutic intervention
      in inflammation-related diseases. They also show how compound 1h regulates
      inflammation and suggest it may be a new source for the development of anti
      inflammatory agents to ameliorate inflammation- and NLRP3 inflammasome-related
      diseases. 

PMID- 24116149
TI  - Genetically based location from triploid populations and gene ontology of a 3.3
      mb genome region linked to Alternaria brown spot resistance in citrus reveal
      clusters of resistance genes.
AB  - Genetic analysis of phenotypical traits and marker-trait association in polyploid
      species is generally considered as a challenge. In the present work, different
      approaches were combined taking advantage of the particular genetic structures of
      2n gametes resulting from second division restitution (SDR) to map a genome
      region linked to Alternaria brown spot (ABS) resistance in triploid citrus
      progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of
      the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces
      necrotic lesions on fruit and young leaves, defoliation and fruit drop in
      susceptible genotypes. It is a strong concern for triploid breeding programs
      aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance
      of susceptibility, proposed on the basis of diploid population studies, was
      corroborated in triploid progeny. Bulk segregant analysis coupled with genome
      scan using a large set of genetically mapped SNP markers and targeted genetic
      mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a
      3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome
      III. Clusters of resistance genes were identified by gene ontology analysis of
      this genomic region. Some of these genes are good candidates to control the
      dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for
      efficient early marker-assisted selection of ABS resistant hybrids. 

PMID- 24116150
TI  - BAC-pool sequencing and analysis of large segments of A12 and D12 homoeologous
      chromosomes in upland cotton.
AB  - Although new and emerging next-generation sequencing (NGS) technologies have
      reduced sequencing costs significantly, much work remains to implement them for
      de novo sequencing of complex and highly repetitive genomes such as the
      tetraploid genome of Upland cotton (Gossypium hirsutum L.). Herein we report the
      results from implementing a novel, hybrid Sanger/454-based BAC-pool sequencing
      strategy using minimum tiling path (MTP) BACs from Ctg-3301 and Ctg-465, two
      large genomic segments in A12 and D12 homoeologous chromosomes (Ctg). To enable
      generation of longer contig sequences in assembly, we implemented a hybrid
      assembly method to process ~35x data from 454 technology and 2.8-3x data from
      Sanger method. Hybrid assemblies offered higher sequence coverage and better
      sequence assemblies. Homology studies revealed the presence of retrotransposon
      regions like Copia and Gypsy elements in these contigs and also helped in
      identifying new genomic SSRs. Unigenes were anchored to the sequences in Ctg-3301
      and Ctg-465 to support the physical map. Gene density, gene structure and protein
      sequence information derived from protein prediction programs were used to obtain
      the functional annotation of these genes. Comparative analysis of both contigs
      with Arabidopsis genome exhibited synteny and microcollinearity with a conserved
      gene order in both genomes. This study provides insight about use of MTP-based
      BAC-pool sequencing approach for sequencing complex polyploid genomes with
      limited constraints in generating better sequence assemblies to build reference
      scaffold sequences. Combining the utilities of MTP-based BAC-pool sequencing with
      current longer and short read NGS technologies in multiplexed format would
      provide a new direction to cost-effectively and precisely sequence complex plant
      genomes. 

PMID- 24116151
TI  - Targeting neuroblastoma stem cells with retinoic acid and proteasome inhibitor.
AB  - BACKGROUND: Neuroblastma cell lines contain a side-population of cells which
      express stemness markers. These stem-like cells may represent the potential
      underlying mechanism for resistance to conventional therapy and recurrence of
      neuroblastoma in patients. METHODOLOGY/PRINCIPAL FINDINGS: To develop novel
      strategies for targeting the side-population of neurobastomas, we analyzed the
      effects of 13-cis-retinoic acid (RA) combined with the proteasome inhibitor
      MG132. The short-term action of the treatment was compared with effects after a 5
      day recovery period during which both chemicals were withdrawn. RA induced growth
      arrest and differentiation of SH-SY5Y and SK-N-BE(2) neuroblastoma cell lines.
      Inhibition of the proteasome caused apoptosis in both cell lines, thus, revealing
      the critical role of this pathway in the regulated degradation of proteins
      involved in neuroblastoma proliferation and survival. The combination of RA with
      MG132 induced apoptosis in a dose-dependent manner, in addition to promoting G2/M
      arrest in treated cultures. Interestingly, expression of stem cell markers such
      as Nestin, Sox2, and Oct4 were reduced after the recovery period of combined
      treatment as compared with untreated cells or treated cells with either compound
      alone. Consistent with this, neurosphere formation was significantly impaired by
      the combined treatment of RA and MG132. CONCLUSIONS: Given that stem-like cells
      are associated with resistant to conventional therapy and are thought to be
      responsible for relapse, our results suggest that dual therapy of RA and
      proteasome inhibitor might be beneficial for targeting the side-population of
      cells associated residual disease in high-risk neuroblastoma.

PMID- 24116152
TI  - Structural differences between the avian and human H7N9 hemagglutinin proteins
      are attributable to modifications in salt bridge formation: a computational study
      with implications in viral evolution.
AB  - Influenza A hemagglutinin (HA) is a homotrimeric glycoprotein composed of a
      fibrous globular stem supporting a globular head containing three sialic acid
      binding sites responsible for infection. The H7N9 strain has consistently
      infected an avian host, however, the novel 2013 strain is now capable of
      infecting a human host which would imply that the HA in both strains structurally
      differ. A better understanding of the structural differences between the avian
      and human H7N9 strains may shed light into viral evolution and transmissibility.
      In this study, we elucidated the structural differences between the avian and
      human H7N9 strains. Throughout the study, we generated HA homology models,
      verified the quality of each model, superimposed HA homology models to determine
      structural differences, and, likewise, elucidated the probable cause for these
      structural differences. We detected two different types of structural differences
      between the novel H7N9 human and representative avian strains, wherein, one type
      (Pattern-1) showed three non-overlapping regions while the other type (Pattern-2)
      showed only one non-overlapping region. In addition, we found that superimposed
      HA homology models exhibiting Pattern-1 contain three non-overlapping regions
      designated as: Region-1 (S1571-A1601); Region-3 (R2621-S2651); and Region-4
      (S2701-D2811), whereas, superimposed HA homology models showing Pattern-2 only
      contain one non-overlapping region designated as Region-2 (S1371-S1451). We
      attributed the two patterns we observed to either the presence of salt bridges
      involving the E1141 residue or absence of the R1411:D771 salt bridge.
      Interestingly, comparison between the human H7N7 and H7N9 HA homology models
      showed high structural similarity. We propose that the putative absence of the
      R1411:D771 salt bridge coupled with the putative presence of the E1141:R2621 and
      E1141:K2641 salt bridges found in the 2013 H7N9 HA homology model is associated
      to human-type receptor binding. This highlights the possible significance of HA
      salt bridge formation modifications in viral infectivity, immune escape,
      transmissibility and evolution. 

PMID- 24116153
TI  - Host-parasitoid dynamics and the success of biological control when parasitoids
      are prone to allee effects.
AB  - In sexual organisms, low population density can result in mating failures and
      subsequently yields a low population growth rate and high chance of extinction.
      For species that are in tight interaction, as in host-parasitoid systems,
      population dynamics are primarily constrained by demographic interdependences, so
      that mating failures may have much more intricate consequences. Our main
      objective is to study the demographic consequences of parasitoid mating failures
      at low density and its consequences on the success of biological control. For
      this, we developed a deterministic host-parasitoid model with a mate-finding
      Allee effect, allowing to tackle interactions between the Allee effect and key
      determinants of host-parasitoid demography such as the distribution of parasitoid
      attacks and host competition. Our study shows that parasitoid mating failures at
      low density result in an extinction threshold and increase the domain of
      parasitoid deterministic extinction. When proned to mate finding difficulties,
      parasitoids with cyclic dynamics or low searching efficiency go extinct;
      parasitoids with high searching efficiency may either persist or go extinct,
      depending on host intraspecific competition. We show that parasitoids suitable as
      biocontrol agents for their ability to reduce host populations are particularly
      likely to suffer from mate-finding Allee effects. This study highlights novel
      perspectives for understanding of the dynamics observed in natural host
      parasitoid systems and improving the success of parasitoid introductions. 

PMID- 24116154
TI  - Hybrid adeno-associated viral vectors utilizing transposase-mediated somatic
      integration for stable transgene expression in human cells.
AB  - Recombinant adeno-associated viral (AAV) vectors have been shown to be one of the
      most promising vectors for therapeutic gene delivery because they can induce
      efficient and long-term transduction in non-dividing cells with negligible side
      effects. However, as AAV vectors mostly remain episomal, vector genomes and
      transgene expression are lost in dividing cells. Therefore, to stably transduce
      cells, we developed a novel AAV/transposase hybrid-vector. To facilitate SB
      mediated transposition from the rAAV genome, we established a system in which one
      AAV vector contains the transposon with the gene of interest and the second
      vector delivers the hyperactive Sleeping Beauty (SB) transposase SB100X. Human
      cells were infected with the AAV-transposon vector and the transposase was
      provided in trans either by transient and stable plasmid transfection or by AAV
      vector transduction. We found that groups which received the hyperactive
      transposase SB100X showed significantly increased colony forming numbers
      indicating enhanced integration efficiencies. Furthermore, we found that
      transgene copy numbers in transduced cells were dose-dependent and that
      predominantly SB transposase-mediated transposition contributed to stabilization
      of the transgene. Based on a plasmid rescue strategy and a linear-amplification
      mediated PCR (LAM-PCR) protocol we analysed the SB100X-mediated integration
      profile after transposition from the AAV vector. A total of 1840 integration
      events were identified which revealed a close to random integration profile. In
      summary, we show for the first time that AAV vectors can serve as template for SB
      transposase mediated somatic integration. We developed the first prototype of
      this hybrid-vector system which with further improvements may be explored for
      treatment of diseases which originate from rapidly dividing cells. 

PMID- 24116155
TI  - Two functional variants of IRF5 influence the development of macular edema in
      patients with non-anterior uveitis.
AB  - OBJECTIVE: Interferon (IFN) signaling plays a crucial role in autoimmunity.
      Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of
      the type I interferon induction, has been associated with risk of developing
      several autoimmune diseases. In the current study we aimed to evaluate whether
      three sets of correlated IRF5 genetic variants, independently associated with SLE
      and with different functional roles, are involved in uveitis susceptibility and
      its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640,
      rs2070197 and rs10954213, representative of each group, were genotyped using
      TaqMan(r) allelic discrimination assays in a total of 263 non-anterior uveitis
      patients and 724 healthy controls of Spanish origin. RESULTS: A clear association
      between two of the three analyzed genetic variants, rs2004640 and rs10954213, and
      the absence of macular edema was observed in the case/control analysis (P FDR
      =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19
      2.01, respectively). Consistently, the subphenotype analysis accordingly with the
      presence/absence of this clinical condition also reached statistical significance
      (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI
      95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically
      associated with the lack of macular edema in uveitis patients. CONCLUSION: Our
      results clearly showed for the first time that two functional genetic variants of
      IRF5 may play a role in the development of macular edema in non-anterior uveitis
      patients. Identifying genetic markers for macular edema could lead to the
      possibility of developing novel treatments or preventive therapies.

PMID- 24116156
TI  - Indoor navigation by people with visual impairment using a digital sign system.
AB  - There is a need for adaptive technology to enhance indoor wayfinding by visually
      impaired people. To address this need, we have developed and tested a Digital
      Sign System. The hardware and software consist of digitally-encoded signs widely
      distributed throughout a building, a handheld sign-reader based on an infrared
      camera, image-processing software, and a talking digital map running on a mobile
      device. Four groups of subjects-blind, low vision, blindfolded sighted, and
      normally sighted controls-were evaluated on three navigation tasks. The results
      demonstrate that the technology can be used reliably in retrieving information
      from the signs during active mobility, in finding nearby points of interest, and
      following routes in a building from a starting location to a destination. The
      visually impaired subjects accurately and independently completed the navigation
      tasks, but took substantially longer than normally sighted controls. This fully
      functional prototype system demonstrates the feasibility of technology enabling
      independent indoor navigation by people with visual impairment. 

PMID- 24116157
TI  - Association between RASSF1A promoter methylation and ovarian cancer: a meta
      analysis.
AB  - BACKGROUND: The RAS association domain family protein 1a gene (RASSF1A) is one of
      the tumor suppressor genes (TSG). Inactivation of RASSF1A is critical to the
      pathogenesis of cancer. Aberrant TSG methylation was considered an important
      epigenetic silencing mechanism in the progression of ovarian cancer. A number of
      studies have discussed association between RASSF1A promoter methylation and
      ovarian cancer. However, they were mostly based on a small number of samples and
      showed inconsist results, Therefore, we conducted a meta-analysis to better
      identify the association. METHODS: Eligible studies were identified by searching
      the PubMed, EMBASE, Web of Science, and CNKI databases using a systematic
      searching strategy. We pooled the odds ratio (ORs) from individual studies using
      a fixed-effects model. We performed heterogeneity and publication bias analysis
      simultaneously. RESULTS: Thirteen studies, with 763 ovarian cancer patients and
      438 controls were included in the meta-analysis. The frequencies of RASSF1A
      promoter methylation ranged from 30% to 58% (median is 48%) in the cancer group
      and 0 to 21% (median is 0) in the control group. The frequencies of RASSF1A
      promoter methylation in the cancer group were significantly higher than those in
      the control group. The pooled odds ratio was 11.17 (95% CI = 7.51-16.61) in the
      cancer group versus the corresponding control group under the fixed-effects
      model. CONCLUSION: The results suggested that RASSF1A promoter methylation had a
      strong association with ovarian cancer.

PMID- 24116158
TI  - The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate.
AB  - Protein phosphatase 1 (PP1) binding proteins are quintessential regulators,
      determining substrate specificity and defining subcellular localization and
      activity of the latter. Here, we describe a novel PP1 binding protein, the
      nuclear membrane protein lamina associated polypeptide 1B (LAP1B), which
      interacts with the DYT1 dystonia protein torsinA. The PP1 binding domain in LAP1B
      was here identified as the REVRF motif at amino acids 55-59. The LAP1B:PP1
      complex can be immunoprecipitated from cells in culture and rat cortex and the
      complex was further validated by yeast co-transformations and blot overlay
      assays. PP1, which is enriched in the nucleus, binds to the N-terminal nuclear
      domain of LAP1B, as shown by immunocolocalization and domain specific binding
      studies. PP1 dephosphorylates LAP1B, confirming the physiological relevance of
      this interaction. These findings place PP1 at a key position to participate in
      the pathogenesis of DYT1 dystonia and related nuclear envelope-based diseases. 

PMID- 24116159
TI  - Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.
AB  - BACKGROUND: Cancer spread to other organs is the main cause of death of
      oncological patients. Migration of cancer cells from a primary tumour is the
      crucial step in the complex process of metastasis, therefore blocking this
      process is currently the main treatment strategy. Metastasis inhibitors derived
      from natural products, such as, migrastatin, are very promising anticancer
      agents. Thus, the aim of our study was to investigate the effect of six
      migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary
      adenocarcinoma cell lines isolated from primary tumours and their metastases to
      the lungs. Canine mammary tumours constitute a valuable tool for studying
      multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX
      FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent
      inhibitors of canine mammary cancer cells migration and invasion. These data were
      obtained using the wound healing test, as well as trans-well migration and
      invasion assays. Furthermore, the treatment of cancer cells with the most
      effective compound (MGSTA-6) disturbed binding between filamentous F-actin and
      fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6
      increased the presence of unbound fascin1 and reduced co-localization of F-actin
      and fascin1 in canine cancer cells. Most likely, actin filaments were not cross
      linked by fascin1 and did not generate the typical filopodial architecture of
      actin filaments in response to the activity of MGSTA-6. Thus, administration of
      MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres
      in canine mammary cancer cells, causing inhibition of cancer migration and
      invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6)
      were shown to be promising compounds for inhibition of cancer metastasis. They
      may have beneficial therapeutic effects in cancer therapy in dogs, especially in
      combination with other anticancer drugs. However, further in vivo studies are
      required to verify this hypothesis.

PMID- 24116160
TI  - Co-overexpression of GEP100 and AMAP1 proteins correlates with rapid local
      recurrence after breast conservative therapy.
AB  - A major problem of current cancer research and therapy is prediction of tumor
      recurrence after initial treatment, rather than the simple biological
      characterization of the malignancy and proliferative properties of tumors. Breast
      conservation therapy (BCT) is a well-approved, standard treatment for patients
      with early stages of breast cancer, which consists of lumpectomy and whole-breast
      irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity'
      have been identified to be well correlated with local recurrence after BCT. An
      Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and
      employs AMAP1 as its effector, is crucial for invasion and metastasis of some
      breast cancer cells. This pathway activates beta1 integrins and perturbs E
      cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal
      transdifferentiation (EMT). We here show that expression of the Arf6 pathway
      components statistically correlates with rapid local recurrence after BCT. We
      retrospectively analyzed four hundred seventy-nine patients who received BCT in
      Hokkaido University Hospital, and found 20 patients had local recurrence. We then
      analyzed pathological samples of patients who experienced local recurrence by use
      of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled
      with immunostaining, and found that co-overexpression of GEP100 and AMAP1
      correlates with rapidity of the local recurrence. Their margin-status, node
      positivity, and estrogen receptor (ER)- or progesterone receptor (PgR)-positivity
      did not correlated with the rapidity. This study is the first to show that
      expression of a certain set of proteins correlates with the rapidity of local
      recurrence. Our results are useful not only for prediction, but highlight the
      possibility of developing novel strategies to block local recurrence. We also
      discuss why mRNAs encoding these proteins have not been identified to correlate
      with local recurrence by previous conventional gene expression profiling
      analyses. 

PMID- 24116161
TI  - Grb2 is regulated by foxd3 and has roles in preventing accumulation and
      aggregation of mutant huntingtin.
AB  - Growth factor receptor protein binding protein 2 (Grb2) is known to be associated
      with intracellular growth and proliferation related signaling cascades.
      Huntingtin (Htt), a ubiquitously expressed protein, when mutated, forms toxic
      intracellular aggregates - the hallmark of Huntington's disease (HD). We observed
      an elevated expression of Grb2 in neuronal cells in animal and cell models of HD.
      Grb2 overexpression was predominantly regulated by the transcription factor
      Forkhead Box D3 (Foxd3). Exogenous expression of Grb2 also reduced aggregation of
      mutant Htt in Neuro2A cells. Grb2 is also known to interact with Htt, depending
      on epidermal growth factor receptor (EGFR) activation. Grb2- mutant Htt
      interaction in the contrary, took place in vesicular structures, independent of
      EGFR activation that eventually merged with autophagosomes and activated the
      autophagy machinery helping in autophagosome and lysosome fusion. Grb2, with its
      emerging dual role, holds promise for a survival mechanism for HD. 

PMID- 24116162
TI  - Variation in one residue associated with the metal ion-dependent adhesion site
      regulates alphaIIbbeta3 integrin ligand binding affinity.
AB  - The Asp of the RGD motif of the ligand coordinates with the beta I domain metal
      ion dependent adhesion site (MIDAS) divalent cation, emphasizing the importance
      of the MIDAS in ligand binding. There appears to be two distinct groups of
      integrins that differ in their ligand binding affinity and adhesion ability.
      These differences may be due to a specific residue associated with the MIDAS,
      particularly the beta3 residue Ala(252) and corresponding Ala in the beta1
      integrin compared to the analogous Asp residue in the beta2 and beta7 integrins.
      Interestingly, mutations in the adjacent to MIDAS (ADMIDAS) of integrins
      alpha4beta7 and alphaLbeta2 increased the binding and adhesion abilities compared
      to the wild-type, while the same mutations in the alpha2beta1, alpha5beta1,
      alphaVbeta3, and alphaIIbbeta3 integrins demonstrated decreased ligand binding
      and adhesion. We introduced a mutation in the alphaIIbbeta3 to convert this MIDAS
      associated Ala(252) to Asp. By combination of this mutant with mutations of one
      or two ADMIDAS residues, we studied the effects of this residue on ligand binding
      and adhesion. Then, we performed molecular dynamics simulations on the wild-type
      and mutant alphaIIbbeta3 integrin beta I domains, and investigated the dynamics
      of metal ion binding sites in different integrin-RGD complexes. We found that the
      tendency of calculated binding free energies was in excellent agreement with the
      experimental results, suggesting that the variation in this MIDAS associated
      residue accounts for the differences in ligand binding and adhesion among
      different integrins, and it accounts for the conflicting results of ADMIDAS
      mutations within different integrins. This study sheds more light on the role of
      the MIDAS associated residue pertaining to ligand binding and adhesion and
      suggests that this residue may play a pivotal role in integrin-mediated cell
      rolling and firm adhesion. 

PMID- 24116163
TI  - Identification of five serum protein markers for detection of ovarian cancer by
      antibody arrays.
AB  - BACKGROUND: Protein and antibody arrays have emerged as a promising technology to
      study protein expression and protein function in a high-throughput manner. These
      arrays also represent a new opportunity to profile protein expression levels in
      cancer patients' samples and to identify useful biosignatures for clinical
      diagnosis, disease classification, prediction, drug development and patient care.
      We applied antibody arrays to discover a panel of proteins which may serve as
      biomarkers to distinguish between patients with ovarian cancer and normal
      controls. METHODOLOGY/PRINCIPAL FINDINGS: Using a case-control study design of 34
      ovarian cancer patients and 53 age-matched healthy controls, we profiled the
      expression levels of 174 proteins using antibody array technology and determined
      the CA125 level using ELISA. The expression levels of those proteins were
      analyzed using 3 discriminant methods, including artificial neural network,
      classification tree and split-point score analysis. A panel of 5 serum protein
      markers (MSP-alpha, TIMP-4, PDGF-R alpha, and OPG and CA125) was identified,
      which could effectively detect ovarian cancer with high specificity (95%) and
      high sensitivity (100%), with AUC =0.98, while CA125 alone had an AUC of 0.87.
      CONCLUSIONS/SIGNIFICANCE: Our pilot study has shown the promising set of 5 serum
      markers for ovarian cancer detection.

PMID- 24116164
TI  - Urotensin II inhibits skeletal muscle glucose transport signaling pathways via
      the NADPH oxidase pathway.
AB  - Our previous studies have demonstrated that the urotensin (UII) and its receptor
      are up-regulated in the skeletal muscle of mice with type II diabetes mellitus
      (T2DM), but the significance of UII in skeletal muscle insulin resistance remains
      unknown. The purpose of this study was to investigate the effect of UII on NADPH
      oxidase and glucose transport signaling pathways in the skeletal muscle of mice
      with T2DM and in C2C12 mouse myotube cells. KK/upj-AY/J mice (KK) mice were
      divided into the following groups: KK group, with saline treatment for 2 weeks;
      KK+ urantide group, with daily 30 ug/kg body weight injections over the same time
      period of urantide, a potent urotensin II antagonist peptide; Non-diabetic
      C57BL/6J mice were used as normal controls. After urantide treatment, mice were
      subjected to an intraperitoneal glucose tolerance test, in addition to
      measurements of the levels of ROS, NADPH oxidase and the phosphorylated AKT, PKC
      and ERK. C2C12 cells were incubated with serum-free DMEM for 24 hours before
      conducting the experiments, and then administrated with 100 nM UII for 2 hours or
      24 hours. Urantide treatment improved glucose tolerance, decreased the
      translocation of the NADPH subunits p40-phox and p47-phox, and increased levels
      of the phosphorylated PKC, AKT and ERK. In contrast, UII treatment increased ROS
      production and p47-phox and p67-phox translocation, and decreased the
      phosphorylated AKT, ERK1/2 and p38MAPK; Apocynin abrogated this effect. In
      conclusion, UII increased ROS production by NADPH oxidase, leading to the
      inhibition of signaling pathways involving glucose transport, such as
      AKT/PKC/ERK. Our data imply a role for UII at the molecular level in glucose
      homeostasis, and possibly in skeletal muscle insulin resistance in T2DM. 

PMID- 24116165
TI  - Inhibition of phenylpropanoid biosynthesis in Artemisia annua L.: a novel
      approach to reduce oxidative browning in plant tissue culture.
AB  - Oxidative browning is a common and often severe problem in plant tissue culture
      systems caused by the accumulation and oxidation of phenolic compounds. The
      current study was conducted to investigate a novel preventative approach to
      address this problem by inhibiting the activity of the phenylalanine ammonia
      lyase enzyme (PAL), thereby reducing the biosynthesis of phenolic compounds. This
      was accomplished by incorporating 2-aminoindane-2-phosphonic acid (AIP), a
      competitive PAL inhibitor, into culture media of Artemisia annua as a model
      system. Addition of AIP into culture media resulted in significant reductions in
      visual tissue browning, a reduction in total phenol content, as well as
      absorbance and autoflourescence of tissue extracts. Reduced tissue browning was
      accompanied with a significant increase in growth on cytokinin based medium.
      Microscopic observations demonstrated that phenolic compounds accumulated in
      discrete cells and that these cells were more prevalent in brown tissue. These
      cells were highly plasmolyzed and often ruptured during examination,
      demonstrating a mechanism in which phenolics are released into media in this
      system. These data indicate that inhibiting phenylpropanoid biosynthesis with AIP
      is an effective approach to reduce tissue browning in A. annua. Additional
      experiments with Ulmus americana and Acer saccharum indicate this approach is
      effective in many species and it could have a wide application in systems where
      oxidative browning restricts the development of biotechnologies. 

PMID- 24116167
TI  - Breeding based remobilization of Tol2 transposon in Xenopus tropicalis.
AB  - Xenopus is a powerful model for studying a diverse array of biological processes.
      However, despite multiple methods for transgenesis, relatively few transgenic
      reporter lines are available and commonly used. Previous work has demonstrated
      that transposon based strategies are effective for generating transgenic lines in
      both invertebrate and vertebrate systems. Here we show that the Tol2 transposon
      can be remobilized in the genome of X. tropicalis and passed through the germline
      via a simple breeding strategy of crossing transposase expressing and transposon
      lines. This remobilization system provides another tool to exploit transgenesis
      and opens new opportunities for gene trap and enhancer trap strategies. 

PMID- 24116166
TI  - Elucidation of substrate specificity in Aspergillus nidulans UDP-galactose-4
      epimerase.
AB  - The frequency of invasive fungal infections has rapidly increased in recent
      years. Current clinical treatments are experiencing decreased potency due to
      severe host toxicity and the emergence of fungal drug resistance. As such, new
      targets and their corresponding synthetic pathways need to be explored for drug
      development purposes. In this context, galactofuranose residues, which are
      employed in fungal cell wall construction, but are notably absent in animals,
      represent an appealing target. Herein we present the structural and biochemical
      characterization of UDP-galactose-4-epimerase from Aspergillus nidulans which
      produces the precursor UDP-galactopyranose required for galactofuranose
      synthesis. Examination of the structural model revealed both NAD(+) and UDP
      glucopyranose were bound within the active site cleft in a near identical fashion
      to that found in the Human epimerase. Mutational studies on the conserved
      catalytic motif support a similar mechanism to that established for the Human
      counterpart is likely operational within the A. nidulans epimerase. While the K m
      and k cat for the enzyme were determined to be 0.11 mM and 12.8 s(-1),
      respectively, a single point mutation, namely L320C, activated the enzyme towards
      larger N-acetylated substrates. Docking studies designed to probe active site
      affinity corroborate the experimentally determined activity profiles and support
      the kinetic inhibition results. 

PMID- 24116168
TI  - microRNAs in circulation are altered in response to influenza A virus infection
      in humans.
AB  - Changes in microRNA expression have been detected in vitro in influenza infected
      cells, yet little is known about them in patients. microRNA profiling was
      performed on whole blood of H1N1 patients to identify signature microRNAs to
      better understand the gene regulation involved and possibly improve diagnosis.
      Total RNA extracted from blood samples of influenza infected patients and healthy
      controls were subjected to microRNA microarray. Expression profiles of
      circulating microRNAs were altered and distinctly different in influenza
      patients. Expression of highly dysregulated microRNAs were validated using
      quantitative PCR. Fourteen highly dysregulated miRNAs, identified from the blood
      of influenza infected patients, provided a clear distinction between infected and
      healthy individuals. Of these, expression of miR-1260, -26a, -335*, -576-3p, -628
      3p and -664 were consistently dysregulated in both whole blood and H1N1 infected
      cells. Potential host and viral gene targets were identified and the impact of
      microRNA dysregulation on the host proteome was studied. Consequences of their
      altered expression were extrapolated to changes in the host proteome expression.
      These highly dysregulated microRNAs may have crucial roles in influenza
      pathogenesis and are potential biomarkers of influenza. 

PMID- 24116169
TI  - Development of a novel trap for the collection of black flies of the Simulium
      ochraceum complex.
AB  - BACKGROUND: Human landing collections are currently the standard method for
      collecting onchocerciasis vectors in Africa and Latin America. As part of the
      efforts to develop a trap to replace human landing collections for the monitoring
      and surveillance of onchocerciasis transmission, comprehensive evaluations of
      several trap types were conducted to assess their ability to collect Simulium
      ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in
      Latin America. METHODOLOGY/PRINCIPAL FINDINGS: Diverse trap designs with numerous
      modifications and bait variations were evaluated for their abilities to collect
      S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A
      novel trap dubbed the "Esperanza window trap" showed particular promise over
      other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor
      components) a pair of Esperanza window traps collected numbers of S. Ochraceum
      s.l. females similar to those collected by a team of vector collectors.
      CONCLUSIONS/SIGNIFICANCE: The Esperanza window trap, when baited with chemical
      lures and CO2 can be used to collect epidemiologically significant numbers of
      Simulium ochraceum s.l., potentially serving as a replacement for human landing
      collections for evaluation of the transmission of O. volvulus.

PMID- 24116171
TI  - Genetic variation and combining ability analysis of bruising sensitivity in
      Agaricus bisporus.
AB  - Advanced button mushroom cultivars that are less sensitive to mechanical bruising
      are required by the mushroom industry, where automated harvesting still cannot be
      used for the fresh mushroom market. The genetic variation in bruising sensitivity
      (BS) of Agaricus bisporus was studied through an incomplete set of diallel
      crosses to get insight in the heritability of BS and the combining ability of the
      parental lines used and, in this way, to estimate their breeding value. To this
      end nineteen homokaryotic lines recovered from wild strains and cultivars were
      inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under
      controlled conditions, and the BS of these hybrids was assessed. BS was shown to
      be a trait with a very high heritability. The results also showed that brown
      hybrids were generally less sensitive to bruising than white hybrids. The diallel
      scheme allowed to estimate the general combining ability (GCA) for each
      homokaryotic parental line and to estimate the specific combining ability (SCA)
      of each hybrid. The line with the lowest GCA is seen as the most attractive donor
      for improving resistance to bruising. The line gave rise to hybrids sensitive to
      bruising having the highest GCA value. The highest negative SCA possibly
      indicates heterosis effects for resistance to bruising. This study provides a
      foundation for estimating breeding value of parental lines to further study the
      genetic factors underlying bruising sensitivity and other quality-related traits,
      and to select potential parental lines for further heterosis breeding. The
      approach of studying combining ability in a diallel scheme was used for the first
      time in button mushroom breeding. 

PMID- 24116170
TI  - Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell
      factor-activated pathways.
AB  - Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1
      (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for
      the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT
      and IGF1-IGF1R signaling are also activated in several cancers including
      gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine
      gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells
      of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation
      between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and
      KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric
      muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX
      2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein
      and mRNA expression and promoter activity by activating several signaling
      pathways including AKT-mediated glycogen synthase kinase-3beta inhibition
      (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating
      mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring
      transcriptional activation at the Kitl promoter including increased histone H3/H4
      acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation
      and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or
      RNA interference-mediated inhibition of chromatin modifiers we demonstrated that
      these changes have the predicted impact on KITLG expression. KITLG knock-down and
      immunoneutralization inhibited the proliferation of GIST cells expressing wild
      type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We
      conclude that membrane-to-nucleus signaling involving GSK3i establishes a
      previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which
      is active in both physiologic and oncogenic contexts and can be exploited for
      therapeutic purposes.

PMID- 24116172
TI  - The expression of CD90/Thy-1 in hepatocellular carcinoma: an in vivo and in vitro
      study.
AB  - Although the CD90 (Thy-1) was proposed as biomarker of several tumors and cancer
      stem cells, the involvement of this molecule in the progression of hepatocellular
      carcinoma (HCC) and other less frequent hepatic neoplasms is still undefined. The
      distribution of CD90 was investigated both in in vivo (human tissues samples) and
      in vitro (human HCC cell line JHH-6). A total of 67 liver tumors were analyzed:
      51 HCC, 6 cholangiocarcinoma and 10 hepatoblastoma. In all cases, paired tissue
      sample of both the tumor and cirrhotic liver was available. Hepatic tissue
      obtained in 12 healthy livers was used as control. CD90 gene expression was
      studied by RT-qPCR, protein expression was assessed by quantitative Western Blot,
      immunofluorescence and flow cytometry. The CD90 expression analysis showed a
      significant increment in tumor compared to both its paired cirrhotic tissue and
      normal liver (p<0.05 and p<0.001, respectively). This increase was accompanied by
      the up-regulation of stromal component in the cancer, as demonstrated by alpha
      smooth muscle actin staining. In vitro analysis of JHH-6 cell line showed a
      higher proliferation capacity of CD90(+) compared to CD90(-) cells (p<0.001),
      also noticed in 3D clonogenic assay (p<0.05), associated by a significant higher
      expression of the promoting factors (hepatocyte growth factor, fibroblast
      associated protein and alpha smooth muscle actin 2). A higher expression of the
      breast cancer resistance protein was found in CD90(+) subpopulation while the
      multidrug resistance protein 1 showed an opposite behavior. Collectively, these
      results point to the importance of CD90 in the HCC. 

PMID- 24116173
TI  - A novel heavy domain antibody library with functionally optimized complementarity
      determining regions.
AB  - Today a number of synthetic antibody libraries of different formats have been
      created and used for the selection of a large number of recombinant antibodies.
      One of the determining factors for successful isolation of recombinant antibodies
      from libraries lies in the quality of the libraries i.e. the number of correctly
      folded, functional antibodies contained in the library. Here, we describe the
      construction of a novel, high quality, synthetic single domain antibody library
      dubbed Predator. The library is based on the HEL4 domain antibody with the
      addition of recently reported mutations concerning the amino acid composition at
      positions critical for the folding characteristics and aggregation propensities
      of domain antibodies. As a unique feature, the CDR3 of the library was designed
      to mimic the natural human immune response by designating amino acids known to be
      prevalent in functional antibodies to the diversity in CDR3. CDR randomizations
      were performed using trinucleotide synthesis to avoid the presence of stop
      codons. Furthermore a novel cycle free elongation method was used for the
      conversion of the synthesized single stranded DNA containing the randomized CDRs
      into double stranded DNA of the library. In addition a modular approach has been
      adopted for the scaffold in which each CDR region is flanked by unique
      restrictions sites, allowing easy affinity maturation of selected clones by CDR
      shuffling. To validate the quality of the library, one round phage display
      selections were performed on purified antigens and highly complex antigen
      mixtures such as cultured eukaryotic cells resulting in several specific binders.
      The further characterization of some of the selected clones, however, indicates a
      reduction in thermodynamic stability caused by the inclusion the additional
      mutations to the HEL4 scaffold. 

PMID- 24116174
TI  - Dynamics of Bcl-xL in water and membrane: molecular simulations.
AB  - The Bcl2 family of proteins is capable of switching the apoptotic machinery by
      directly controlling the release of apoptotic factors from the mitochondrial
      outer membrane. They have 'pro' and 'anti'-apoptotic subgroups of proteins which
      antagonize each other's function; however a detailed atomistic understanding of
      their mechanisms based on the dynamical events, particularly in the membrane, is
      lacking. Using molecular dynamics simulations totaling 1.6us we outline the major
      differences between the conformational dynamics in water and in membrane. Using
      implicit models of solvent and membrane, the simulated results reveal a picture
      that is in agreement with the 'hit-and run' concept which states that BH3-only
      peptides displace the tail (which acts as a pseudo substrate of the protein
      itself) from its binding pocket; this helps the membrane association of the
      protein after which the BH3 peptide becomes free. From simulations, Bcl-xL
      appears to be auto-inhibited by its C-terminal tail that embeds into and covers
      the hydrophobic binding pocket. However the tail is unable to energetically
      compete with BH3-peptides in water. In contrast, in the membrane, neither the
      tail nor the BH3-peptides are stable in the binding pocket and appear to be
      easily dissociated off as the pocket expands in response to the hydrophobic
      environment. This renders the binding pocket large and open, thus receptive to
      interactions with other protein partners. Principal components of the motions are
      dramatically different in the aqueous and in the membrane environments and
      provide clues regarding the conformational transitions that Bcl-xL undergoes in
      the membrane, in agreement with the biochemical data. 

PMID- 24116175
TI  - Value addition in the efficacy of conventional antibiotics by Nisin against
      Salmonella.
AB  - Frequent and indiscriminate use of existing battery of antibiotics has led to the
      development of multi drug resistant (MDR) strains of pathogens. As decreasing the
      concentration of the antibiotic required to treat Salmonellosis might help in
      combating the development of resistant strains, the present study was designed to
      assess the synergistic effects, if any, of nisin, in combination with
      conventional anti-Salmonella antibiotics against Salmonella enterica serovar
      Typhimurium. Minimum inhibitory concentrations (MICs) of the selected
      antimicrobial agents were determined by micro and macro broth dilution assays. In
      vitro synergy between the agents was evaluated by radial diffusion assay,
      fractional inhibitory concentration (FIC) index (checkerboard test) and time-kill
      assay. Scanning electron microscopy (SEM) was also performed to substantiate the
      effect of the combinations. In-vivo synergistic efficacy of the combinations
      selected on the basis of in-vitro results was also evaluated in the murine model,
      in terms of reduction in the number of Salmonellae in liver, spleen and
      intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have
      additive effects, whereas the combinations of nisin-ceftriaxone and nisin
      cefotaxime were found to be highly synergistic against serovar Typhimurium as
      evident by checkerboard test and time-kill assay. SEM results revealed marked
      changes on the outer membrane of the bacterial cells treated with various
      combinations. In-vivo synergy was evident from the larger log unit decreases in
      all the target organs of mice treated with the combinations than in those treated
      with drugs alone. This study thus highlights that nisin has the potential to act
      in conjunction with conventional antibiotics at much lower MICs. These
      observations seem to be significant, as reducing the therapeutic concentrations
      of antibiotics may be a valuable strategy for avoiding/reducing the development
      of emerging antibiotic resistance. Value added potential of nisin in the efficacy
      of conventional antibiotics may thus be exploited not only against Salmonella but
      against other Gram-negative infections as well. 

PMID- 24116176
TI  - Predicting risk-taking behavior from prefrontal resting-state activity and
      personality.
AB  - Risk-taking is subject to considerable individual differences. In the current
      study, we tested whether resting-state activity in the prefrontal cortex and
      trait sensitivity to reward and punishment can help predict risk-taking behavior.
      Prefrontal activity at rest was assessed in seventy healthy volunteers using
      electroencephalography, and compared to their choice behavior on an economic risk
      taking task. The Behavioral Inhibition System/Behavioral Activation System scale
      was used to measure participants' trait sensitivity to reward and punishment. Our
      results confirmed both prefrontal resting-state activity and personality traits
      as sources of individual differences in risk-taking behavior. Right-left
      asymmetry in prefrontal activity and scores on the Behavioral Inhibition System
      scale, reflecting trait sensitivity to punishment, were correlated with the level
      of risk-taking on the task. We further discovered that scores on the Behavioral
      Inhibition System scale modulated the relationship between asymmetry in
      prefrontal resting-state activity and risk-taking. The results of this study
      demonstrate that heterogeneity in risk-taking behavior can be traced back to
      differences in the basic physiology of decision-makers' brains, and suggest that
      baseline prefrontal activity and personality traits might interplay in guiding
      risk-taking behavior. 

PMID- 24116178
TI  - Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible
      structure-specific plasticity process in 6-OHDA lesioned rats.
AB  - The endocannabinoid system has been implicated in several neurobiological
      processes, including neurodegeneration, neuroprotection and neuronal plasticity.
      The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the
      circuitry that is mostly affected in Parkinson's Disease (PD). Some studies show
      variation of CB1 expression in basal ganglia in different animal models of PD,
      however the results are quite controversial, due to the differences in the
      procedures employed to induce the parkinsonism and the periods analyzed after the
      lesion. The present study evaluated the CB1 expression in four basal ganglia
      structures, namely striatum, external globus pallidus (EGP), internal globus
      pallidus (IGP) and substantia nigra pars reticulata (SNpr) of rats 1, 5, 10, 20,
      and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that
      causes retrograde dopaminergic degeneration. We also investigated tyrosine
      hydroxylase (TH), parvalbumin, calbindin and glutamic acid decarboxylase (GAD)
      expression to verify the status of dopaminergic and GABAergic systems. We
      observed a structure-specific modulation of CB1 expression at different periods
      after lesions. In general, there were no changes in the striatum, decreased CB1
      in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained
      over time. No changes in GAD and parvalbumin expression were observed in basal
      ganglia, whereas TH levels were decreased and the calbindin increased in striatum
      in short periods after lesion. We believe that the structure-specific variation
      of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a
      compensatory process involving the GABAergic transmission, which is impaired due
      to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and
      calbindin expression may represent a plasticity process in this PD model. 

PMID- 24116177
TI  - Volatile emissions from Mycobacterium avium subsp. paratuberculosis mirror
      bacterial growth and enable distinction of different strains.
AB  - Control of paratuberculosis in livestock is hampered by the low sensitivity of
      established direct and indirect diagnostic methods. Like other bacteria,
      Mycobacterium avium subsp. paratuberculosis (MAP) emits volatile organic
      compounds (VOCs). Differences of VOC patterns in breath and feces of infected and
      not infected animals were described in first pilot experiments but detailed
      information on potential marker substances is missing. This study was intended to
      look for characteristic volatile substances in the headspace of cultures of
      different MAP strains and to find out how the emission of VOCs was affected by
      density of bacterial growth. One laboratory adapted and four field strains, three
      of MAP C-type and one MAP S-type were cultivated on Herrold's egg yolk medium in
      dilutions of 10(-0), 10(-2), 10(-4) and 10(-6). Volatile substances were pre
      concentrated from the headspace over the MAP cultures by means of Solid Phase
      Micro Extraction (SPME), thermally desorbed from the SPME fibers and separated
      and identified by means of GC-MS. Out of the large number of compounds found in
      the headspace over MAP cultures, 34 volatile marker substances could be
      identified as potential biomarkers for growth and metabolic activity. All five
      MAP strains could clearly be distinguished from blank culture media by means of
      emission patterns based on these 34 substances. In addition, patterns of
      volatiles emitted by the reference strain were significantly different from the
      field strains. Headspace concentrations of 2-ethylfuran, 2-methylfuran, 3
      methylfuran, 2-pentylfuran, ethyl acetate, 1-methyl-1-H-pyrrole and
      dimethyldisulfide varied with density of bacterial growth. Analysis of VOCs
      emitted from mycobacterial cultures can be used to identify bacterial growth and,
      in addition, to differentiate between different bacterial strains. VOC emission
      patterns may be used to approximate bacterial growth density. In a perspective
      volatile marker substances could be used to diagnose MAP infections in animals
      and to identify different bacterial strains and origins. 

PMID- 24116179
TI  - Sexual dimorphisms in the dermal denticles of the lesser-spotted catshark,
      Scyliorhinus canicula (Linnaeus, 1758).
AB  - The dermal layers of several elasmobranch species have been shown to be sexually
      dimorphic. Generally, when this occurs the females have thicker dermal layers
      compared to those of males. This sexual dimorphism has been suggested to occur as
      a response to male biting during mating. Although male biting as a copulatory
      behaviour in Scyliorhinus canicula has been widely speculated to occur, only
      relatively recently has this behaviour been observed. Male S. canicula use their
      mouths to bite the female's pectoral and caudal fins as part of their pre
      copulatory behaviour and to grasp females during copulation. Previous work has
      shown that female S. canicula have a thicker epidermis compared to that of males.
      The structure of the dermal denticles in females may also differ from that of
      males in order to protect against male biting or to provide a greater degree of
      friction in order to allow the male more purchase. This study reveals that the
      length, width and density of the dermal denticles of mature male and female S.
      canicula are sexually dimorphic across the integument in areas where males have
      been observed to bite and wrap themselves around females (pectoral fin, area
      posterior to the pectoral fin, caudal fin, and pelvic girdle). No significant
      differences in the dermal denticle dimensions were found in other body areas
      examined (head, dorsal skin and caudal peduncle). Sexually dimorphic dermal
      denticles in mature S. canicula could be a response to male biting/wrapping as
      part of the copulatory process. 

PMID- 24116180
TI  - Circulating adipocytokines and chronic kidney disease.
AB  - BACKGROUND: Adipokines have been associated with atherosclerotic heart disease,
      which shares many common risk factors with chronic kidney disease (CKD), but
      their relationship with CKD has not been well characterized. METHODS: We
      investigated the association of plasma leptin, resistin and adiponectin with CKD
      in 201 patients with CKD and 201 controls without. CKD was defined as estimated
      glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) or presence of
      albuminuria. Quantile regression and logistic regression models were used to
      examine the association between adipokines and CKD adjusting for multiple
      confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2
      vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL,
      p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds
      ratio (95% confidence interval) of CKD comparing the highest tertile to the lower
      two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin.
      Median adiponectin was not significantly different in cases and controls, but the
      odds ratio comparing the highest tertile to the lower two tertiles was
      significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and
      adiponectin were independently associated with lower eGFR and higher urinary
      albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are
      independently and significantly associated with the risk and severity of CKD.
      Longitudinal studies are warranted to evaluate the prospective relationship of
      adipocytokines to the development and progression of CKD.

PMID- 24116181
TI  - The MET13 methylenetetrahydrofolate reductase gene is essential for infection
      related morphogenesis in the rice blast fungus Magnaporthe oryzae.
AB  - Methylenetetrahydrofolate reductases (MTHFRs) play a key role in the biosynthesis
      of methionine in both prokaryotic and eukaryotic organisms. In this study, we
      report the identification of a novel T-DNA-tagged mutant WH672 in the rice blast
      fungus Magnaporthe oryzae, which was defective in vegetative growth, conidiation
      and pathogenicity. Analysis of the mutation confirmed a single T-DNA insertion
      upstream of MET13, which encodes a 626-amino-acid protein encoding a MTHFR.
      Targeted gene deletion of MET13 resulted in mutants that were non-pathogenic and
      significantly impaired in aerial growth and melanin pigmentation. All phenotypes
      associated with Deltamet13 mutants could be overcome by addition of exogenous
      methionine. The M. oryzae genome contains a second predicted MTHFR-encoding gene,
      MET12. The deduced amino acid sequences of Met13 and Met12 share 32% identity.
      Interestingly, Deltamet12 mutants produced significantly less conidia compared
      with the isogenic wild-type strain and grew very poorly in the absence of
      methionine, but were fully pathogenic. Deletion of both genes resulted in
      Deltamet13Deltamet12 mutants that showed similar phenotypes to single Deltamet13
      mutants. Taken together, we conclude that the MTHFR gene, MET13, is essential for
      infection-related morphogenesis by the rice blast fungus M. oryzae. 

PMID- 24116182
TI  - Self versus family ratings of the frontal systems behaviour scale and measured
      executive functions: adult outcomes following childhood traumatic brain injury.
AB  - Traumatic brain injury (TBI) frequently occurs during childhood and adolescence
      with long-term neuropsychological and behavioral effects. Greater personal
      awareness of injury is associated with better outcomes. However, personal
      awareness is often assessed using ratings obtained from family members or
      significant others. Surprisingly, the accuracy of family-ratings compared with
      self-ratings has not been well studied in the TBI population. Thus, the purpose
      of this study was to examine self versus family-ratings of frontal dysfunction
      and secondly, the association between self/family reported frontal dysfunction
      and measured executive function outcomes. A total of 60 participants,
      approximately 10 years post-TBI, comprised 3 groups including; moderate/severe
      TBI (N=26; mean age 22.9, SD=3.0), mild TBI (N=20; mean age, 21.7, SD=2.7), and
      control (N=14: mean age, 21.6, SD=3.7). Neuropsychological testing was used to
      obtain domain scores for executive function and working memory/attention for each
      participant, and nominated family members and participants with TBI were asked to
      complete the Frontal Systems Behaviour Scale (FrSBe), consisting of three sub
      scales; apathy, disinhibition, and executive dysfunction. Using the FrSBe there
      was no significant difference between the groups in executive function score, but
      the moderate/severe and mild groups had significantly lower working
      memory/attention scores compared with the control group (p<0.05). Repeated
      measures analysis of variance showed higher self-ratings on all sub-scales
      compared with family in each group (p<0.05). Scores on executive function and
      working memory/attention domains correlated with self, but not family reported
      executive dysfunction. Self-rated executive dysfunction explained 36% of the
      variance in executive function (p<0.001). While agreement between self-rated and
      family-rated total FrSBe scores was significant in all groups (p<0.001), our
      results showed that self-ratings were of higher predictive utility for executive
      functioning compared with family ratings. Further, at 10 years post-TBI, patients
      show greater awareness of deficits compared with family who rate consistently
      closer to the normal functioning range. 

PMID- 24116183
TI  - Comparative proteomic analysis of the hepatic response to heat stress in Muscovy
      and Pekin ducks: insight into thermal tolerance related to energy metabolism.
AB  - The Pekin duck, bred from the mallard (Anas platyrhynchos) in china, is one of
      the most famous meat duck species in the world. However, it is more sensitive to
      heat stress than Muscovy duck, which is believed to have originated in South
      America. With temperature raising, mortality, laying performance, and meat
      quality of the Pekin duck are severely affected. This study aims to uncover the
      temperature-dependent proteins of two duck species using comparative proteomic
      approach. Duck was cultured under 39 degrees C +/- 0.5 degrees C for 1 h, and
      then immediately returned to 20 degrees C for a 3 h recovery period, the liver
      proteins were extracted and electrophoresed in two-dimensional mode. After
      analysis of gel images, 61 differentially expressed proteins were detected, 54
      were clearly identified by MALDI TOF/TOF MS. Of the 54 differentially expressed
      protein spots identified, 7 were found in both species, whereas 47 were species
      specific (25 in Muscovy duck and 22 in Pekin duck). As is well known, chaperone
      proteins, such as heat shock protein (HSP) 70 and HSP10, were abundantly up
      regulated in both species in response to heat stress. However, we also found that
      several proteins, such as alpha-enolase, and S-adenosylmethionine synthetase,
      showed different expression patterns in the 2 duck species. The enriched
      biological processes were grouped into 3 main categories according to gene
      ontology analysis: cell death and apoptosis (20.93%), amino acid metabolism
      (13.95%) and oxidation reduction (20.93%). The mRNA levels of several
      differentially expressed protein were investigated by real-time RT-PCR. To our
      knowledge, this study is the first to provide insights into the differential
      expression of proteins following heat stress in ducks and enables better
      understanding of possible heat stress response mechanisms in animals. 

PMID- 24116184
TI  - Epistatic Interactions between apolipoprotein E and hemoglobin S Genes in
      regulation of malaria parasitemia.
AB  - Apolipoprotein E is a monomeric protein secreted by the liver and responsible for
      the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3
      isoforms E4, E3 and E2 with APOE E4 associated with higher plasma cholesterol
      levels and increased pathogenesis in several infectious diseases (HIV, HSV).
      Given that cholesterol is an important nutrient for malaria parasites, we
      examined whether APOE E4 was a risk factor for Plasmodium infection, in terms of
      prevalence or parasite density. A cross sectional survey was performed in 508
      children aged 1 to 12 years in Gabon during the wet season. Children were
      screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS)
      polymorphisms. Median parasite densities were significantly higher in APOE E4
      children for Plasmodium spp. densities compared to non-APOE E4 children. When
      stratified for HbS polymorphisms, median Plasmodium spp. densities were
      significantly higher in HbAA children if they had an APOE E4 allele compared to
      those without an APOE E4 allele. When considering non-APOE E4 children, there was
      no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared
      to HbAA phenotypes. No influence of APOE E4 on successful Plasmodium liver cell
      invasion was detected by multiplicity of infection. These results show that the
      APOE E4 allele is associated with higher median malaria parasite densities in
      children likely due to the importance of cholesterol availability to parasite
      growth and replication. Results suggest an epistatic interaction between APOE and
      HbS genes such that sickle cell trait only had an effect on parasite density in
      APOE E4 children. This suggests a linked pathway of regulation of parasite
      density involving expression of these genes. These findings have significance for
      understanding host determinants of regulation of malaria parasite density, the
      design of clinical trials as well as studies of co-infection with Plasmodium and
      other pathogens. 

PMID- 24116185
TI  - High prevalence of HIV, HCV and tuberculosis and associated risk behaviours among
      new entrants of methadone maintenance treatment clinics in Guangdong Province,
      China.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) has been available in Guangdong
      province, China since 2006. This study aims to estimate the prevalence levels of
      HIV, Hepatitis C (HCV), Tuberculosis (TB) and their co-infections and associated
      demographic and risk behaviours among MMT entrants. METHOD: A total of 2296 drug
      users at the time of their MMT enrolment were recruited from four clinics during
      2006-2011. Participants' demographic characteristics, infection status and self
      reported high-risk drug-use and sexual behaviours were surveyed. Log-linear
      contingency analysis was employed to investigate the demographic and behavioural
      differences between gender and drug-user type, while multivariate regression
      analysis was used to identify the associated factors of HIV, HCV and TB
      infections. RESULTS: Female drug users demonstrate significantly higher frequency
      of daily drug consumption (Log-linear contingency analysis, G(2)=10.86, p=0.013)
      and higher proportion of having had sex in the past three months (G(2)=30.22,
      p<0.001) than their male counterparts. Among injecting drug users, females also
      inject (chi(2)=16.15, p=0.001) and share syringes (chi(2)=13.24, p=0.004) more
      frequently than males. Prevalence of HIV, HCV and TB among MMT entrants are 6.3%,
      78.7% and 4.4% respectively. Co-infections of HIV/HCV, HIV/TB, HCV/TB and
      HIV/HCV/TB reportedly infect 5.6%, 0.5%, 3.8% and 0.3% of study participants.
      Infection risks of HIV, HCV and TB are consistently associated with increasing
      length of drug use, injecting drugs, financial dependence and reduced sexual
      activities. CONCLUSION: Injecting drug use is the major contributing factor in
      prevalence levels of HIV, HCV and TB among MMT entrants. Female drug users are
      more disadvantaged in their social status and risk-taking in their drug use
      behaviours than males.

PMID- 24116186
TI  - Insights into the prostanoid pathway in the ovary development of the penaeid
      shrimp Penaeus monodon.
AB  - The prostanoid pathway converts polyunsaturated fatty acids (PUFAs) into
      bioactive lipid mediators, including prostaglandins, thromboxanes and
      prostacyclins, all of which play vital roles in the immune and reproductive
      systems in most animal phyla. In crustaceans, PUFAs and prostaglandins have been
      detected and often associated with female reproductive maturation. However, the
      presence of prostanoid biosynthesis genes remained in question in these species.
      In this study, we outlined the prostanoid pathway in the black tiger shrimp
      Penaeus monodon based on the amplification of nine prostanoid biosynthesis genes:
      cytosolic phospholipase A2, hematopoietic prostaglandin D synthase, glutathione
      dependent prostaglandin D synthase, prostaglandin E synthase 1, prostaglandin E
      synthase 2, prostaglandin E synthase 3, prostaglandin F synthase, thromboxane A
      synthase and cyclooxygenase. TBLASTX analysis confirmed the identities of these
      genes with 51-99% sequence identities to their closest homologs. In addition,
      prostaglandin F2alpha (PGF2alpha), which is a product of the prostaglandin F
      synthase enzyme, was detected for the first time in P. monodon ovaries along with
      the previously identified PUFAs and prostaglandin E2 (PGE2) using RP-HPLC and
      mass-spectrometry. The prostaglandin synthase activity was also observed in
      shrimp ovary homogenates using in vitro activity assay. When prostaglandin
      biosynthesis was examined in different stages of shrimp ovaries, we found that
      the amounts of prostaglandin F synthase gene transcripts and PGF2alpha decreased
      as the ovaries matured. These findings not only indicate the presence of a
      functional prostanoid pathway in penaeid shrimp, but also suggest a possible role
      of the PGF2alpha biosynthesis in shrimp ovarian development. 

PMID- 24116187
TI  - Deletion of the sequence encoding the tail domain of the bone morphogenetic
      protein type 2 receptor reveals a bone morphogenetic protein 7-specific gain of
      function.
AB  - The bone morphogenetic protein (BMP) type II receptor (BMPR2) has a long
      cytoplasmic tail domain whose function is incompletely elucidated. Mutations in
      the tail domain of BMPR2 are found in familial cases of pulmonary arterial
      hypertension. To investigate the role of the tail domain of BMPR2 in BMP
      signaling, we generated a mouse carrying a Bmpr2 allele encoding a non-sense
      mediated decay-resistant mutant receptor lacking the tail domain of Bmpr2. We
      found that homozygous mutant mice died during gastrulation, whereas heterozygous
      mice grew normally without developing pulmonary arterial hypertension. Using
      pulmonary artery smooth muscle cells (PaSMC) from heterozygous mice, we
      determined that the mutant receptor was expressed and retained its ability to
      transduce BMP signaling. Heterozygous PaSMCs exhibited a BMP7-specific gain of
      function, which was transduced via the mutant receptor. Using siRNA knockdown and
      cells from conditional knockout mice to selectively deplete BMP receptors, we
      observed that the tail domain of Bmpr2 inhibits Alk2-mediated BMP7 signaling.
      These findings suggest that the tail domain of Bmpr2 is essential for normal
      embryogenesis and inhibits Alk2-mediated BMP7 signaling in PaSMCs. 

PMID- 24116188
TI  - Maintenance of a living understory enhances soil carbon sequestration in
      subtropical orchards.
AB  - Orchard understory represents an important component of the orchards, performing
      numerous functions related to soil quality, water relations and microclimate, but
      little attention has been paid on its effect on soil C sequestration. In the face
      of global climate change, fruit producers also require techniques that increase
      carbon (C) sequestration in a cost-effective manner. Here we present a case study
      to compare the effects of understory management (sod culture vs. clean tillage)
      on soil C sequestration in four subtropical orchards. The results of a 10-year
      study indicated that the maintenance of sod significantly enhanced the soil C
      stock in the top 1 m of orchard soils. Relative to clean tillage, sod culture
      increased annual soil C sequestration by 2.85 t C ha(-1), suggesting that
      understory management based on sod culture offers promising potential for soil
      carbon sequestration. Considering that China has the largest area of orchards in
      the world and that few of these orchards currently have sod understories, the
      establishment and maintenance of sod in orchards can help China increase C
      sequestration and greatly contribute to achieving CO2 reduction targets at a
      regional scale and potentially at a national scale. 

PMID- 24116189
TI  - Transcriptome-mining for single-copy nuclear markers in ferns.
AB  - BACKGROUND: Molecular phylogenetic investigations have revolutionized our
      understanding of the evolutionary history of ferns-the second-most species-rich
      major group of vascular plants, and the sister clade to seed plants. The general
      absence of genomic resources available for this important group of plants,
      however, has resulted in the strong dependence of these studies on plastid data;
      nuclear or mitochondrial data have been rarely used. In this study, we utilize
      transcriptome data to design primers for nuclear markers for use in studies of
      fern evolutionary biology, and demonstrate the utility of these markers across
      the largest order of ferns, the Polypodiales. PRINCIPAL FINDINGS: We present 20
      novel single-copy nuclear regions, across 10 distinct protein-coding genes:
      ApPEFP_C, cryptochrome 2, cryptochrome 4, DET1, gapCpSh, IBR3, pgiC, SQD1,
      TPLATE, and transducin. These loci, individually and in combination, show strong
      resolving power across the Polypodiales phylogeny, and are readily amplified and
      sequenced from our genomic DNA test set (from 15 diploid Polypodiales species).
      For each region, we also present transcriptome alignments of the focal locus and
      related paralogs-curated broadly across ferns-that will allow researchers to
      develop their own primer sets for fern taxa outside of the Polypodiales. Analyses
      of sequence data generated from our genomic DNA test set reveal strong effects of
      partitioning schemes on support levels and, to a much lesser extent, on topology.
      A model partitioned by codon position is strongly favored, and analyses of the
      combined data yield a Polypodiales phylogeny that is well-supported and
      consistent with earlier studies of this group. CONCLUSIONS: The 20 single-copy
      regions presented here more than triple the single-copy nuclear regions available
      for use in ferns. They provide a much-needed opportunity to assess plastid
      derived hypotheses of relationships within the ferns, and increase our capacity
      to explore aspects of fern evolution previously unavailable to scientific
      investigation.

PMID- 24116190
TI  - Detection of Streptococcus pneumoniae and Haemophilus influenzae type B by real
      time PCR from dried blood spot samples among children with pneumonia: a useful
      approach for developing countries.
AB  - BACKGROUND: Dried blood spot (DBS) is a reliable blood collection method for
      storing samples at room temperature and easily transporting them. We have
      previously validated a Real-Time PCR for detection of Streptococcus pneumoniae in
      DBS. The objective of this study was to apply this methodology for the diagnosis
      of S. pneumoniae and Haemophilus influenzae b (Hib) in DBS samples of children
      with pneumonia admitted to two hospitals in Mozambique and Morocco. METHODS: Ply
      and wzg genes of S. pneumoniae and bexA gene of Hib, were used as targets of Real
      Time PCR. 329 DBS samples of children hospitalized with clinical diagnosis of
      pneumonia were tested. RESULTS: Real-Time PCR in DBS allowed for a significant
      increase in microbiological diagnosis of S. pneumoniae and Hib. When performing
      blood bacterial culture, only ten isolates of S. pneumoniae and none of Hib were
      detected (3.0% positivity rate, IC95% 1.4-5.5%). Real-Time PCR from DBS samples
      increased the detection yield by 4x fold, as 30 S. pneumoniae and 11 Hib cases
      were detected (12.4% positivity rate, IC95% 9.0-16.5%; P<0.001). CONCLUSION: Real
      Time PCR applied in DBS may be a valuable tool for improving diagnosis and
      surveillance of pneumonia caused by S. pneumoniae or Hib in developing countries.

PMID- 24116191
TI  - Structural and functional analyses of DNA-sensing and immune activation by human
      cGAS.
AB  - The detection of cytosolic DNA, derived from pathogens or host cells, by
      cytosolic receptors is essential for appropriate host immune responses. Cyclic
      GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that
      produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING),
      resulting in TBK1-IRF3 pathway activation followed by the production of type I
      interferons. Here we report the crystal structure of human cGAS. The structure
      revealed that a cluster of lysine and arginine residues forms the positively
      charged DNA binding surface of human cGAS, which is important for the STING
      dependent immune activation. A structural comparison with other previously
      determined cGASs and our functional analyses suggested that a conserved zinc
      finger motif and a leucine residue on the DNA binding surface are crucial for the
      DNA-specific immune response of human cGAS, consistent with previous work. These
      structural features properly orient the DNA binding to cGAS, which is critical
      for DNA-induced cGAS activation and STING-dependent immune activation.
      Furthermore, we showed that the cGAS-induced activation of STING also involves
      the activation of the NF-kappaB and IRF3 pathways. Our results indicated that
      cGAS is a DNA sensor that efficiently activates the host immune system by
      inducing two distinct pathways. 

PMID- 24116192
TI  - Atenolol induced HDL-C change in the pharmacogenomic evaluation of
      antihypertensive responses (PEAR) study.
AB  - We sought to identify novel pharmacogenomic markers for HDL-C response to
      atenolol in participants with mild to moderate hypertension. We genotyped 768
      hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive
      Responses (PEAR) study on the Illumina HumanCVD Beadchip. During PEAR,
      participants were randomized to receive atenolol or hydrochlorothiazide. Blood
      pressure and cholesterol levels were evaluated at baseline and after treatment.
      This study focused on participants treated with atenolol monotherapy. Association
      with atenolol induced HDL-C change was evaluated in 232 whites and 152 African
      Americans using linear regression. No SNPs achieved a Bonferroni corrected P
      value. However, we identified 13 regions with consistent association across
      whites and African Americans. The most interesting of these regions were seven
      with prior associations with HDL-C, other metabolic traits, or functional
      implications in the lipid pathway: GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and
      LIPC. Examples are rs2144300 in GALNT2 in whites (P=2.29x10(-4), beta=-1.85
      mg/dL) and rs12595985 in FTO in African Americans (P=2.90x10(-4), beta=4.52
      mg/dL), both with consistent regional association (P<0.05) in the other race
      group. Additionally, baseline GALNT2 expression differed by rs2144300 genotype in
      whites (P=0.0279). In conclusion, we identified multiple gene regions associated
      with atenolol induced HDL-C change that were consistent across race groups,
      several with functional implications or prior associations with HDL-C. 

PMID- 24116193
TI  - Microbial diversity and structure are drivers of the biological barrier effect
      against Listeria monocytogenes in soil.
AB  - Understanding the ecology of pathogenic organisms is important in order to
      monitor their transmission in the environment and the related health hazards. We
      investigated the relationship between soil microbial diversity and the barrier
      effect against Listeria monocytogenes invasion. By using a dilution-to-extinction
      approach, we analysed the consequence of eroding microbial diversity on L.
      monocytogenes population dynamics under standardised conditions of abiotic
      parameters and microbial abundance in soil microcosms. We demonstrated that
      highly diverse soil microbial communities act as a biological barrier against L.
      monocytogenes invasion and that phylogenetic composition of the community also
      has to be considered. This suggests that erosion of diversity may have damaging
      effects regarding circulation of pathogenic microorganisms in the environment. 

PMID- 24116194
TI  - Lymphocytes and macrophages are infected by Theileria equi, but T cells and B
      cells are not required to establish infection in vivo.
AB  - Theileria equi has a biphasic life cycle in horses, with a period of
      intraleukocyte development followed by patent erythrocytic parasitemia that
      causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that
      infect cattle (Theileria parva and Theileria annulata), the intraleukocyte stage
      (schizont) of Theileria equi does not cause uncontrolled host cell proliferation
      or other significant pathology. Nevertheless, schizont-infected leukocytes are of
      interest because of their potential to alter host cell function and because
      immune responses directed against this stage could halt infection and prevent
      disease. Based on cellular morphology, Theileria equi has been reported to infect
      lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected
      cells has yet to be defined. To resolve this knowledge gap in Theileria equi
      pathogenesis, peripheral blood mononuclear cells were infected in vitro and the
      phenotype of infected cells determined using flow cytometry and
      immunofluorescence microscopy. These experiments demonstrated that the host cell
      range of Theileria equi was broader than initially reported and included B
      lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T
      lymphocytes were required to establish infection in vivo, horses affected with
      severe combined immunodeficiency (SCID), which lack functional B and T
      lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses
      developed patent erythrocytic parasitemia, indicating that B and T lymphocytes
      are not necessary to complete the Theileria equi life cycle in vivo. These
      findings suggest that the factors mediating Theileria equi leukocyte invasion and
      intracytoplasmic differentiation are common to several leukocyte subsets and are
      less restricted than for Theileria annulata and Theileria parva. These data will
      greatly facilitate future investigation into the relationships between Theileria
      equi leukocyte tropism and pathogenesis, breed susceptibility, and strain
      virulence. 

PMID- 24116195
TI  - An observational study of patient characteristics associated with the mode of
      admission to acute stroke services in North East, England.
AB  - OBJECTIVE: Effective provision of urgent stroke care relies upon admission to
      hospital by emergency ambulance and may involve pre-hospital redirection. The
      proportion and characteristics of patients who do not arrive by emergency
      ambulance and their impact on service efficiency is unclear. To assist in the
      planning of regional stroke services we examined the volume, characteristics and
      prognosis of patients according to the mode of presentation to local services.
      STUDY DESIGN AND SETTING: A prospective regional database of consecutive acute
      stroke admissions was conducted in North East, England between 01/09/10-30/09/11.
      Case ascertainment and transport mode were checked against hospital coding and
      ambulance dispatch databases. RESULTS: Twelve acute stroke units contributed data
      for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of
      stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by
      private transport or non-emergency ambulance; 252 unknown mode. Emergency
      ambulance patients were older (76 vs 69 years), more likely to be from
      institutional care (10% vs 1%) and experiencing total anterior circulation
      symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency
      admission (11% vs 4%). However patients attending without emergency ambulance had
      lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1%
      vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly
      dependent patients were admitted by emergency ambulance, but none received
      thrombolysis. CONCLUSION: Presentations of new stroke without emergency ambulance
      involvement were not unusual but were associated with a better outcome due to
      younger age, milder neurological impairment and lower levels of pre-stroke
      dependency. Most patients with a high level of pre-stroke dependency arrived by
      emergency ambulance but did not receive thrombolysis. It is important to be aware
      of easily identifiable demographic groups that differ in their potential to gain
      from different service configurations.

PMID- 24116196
TI  - XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but
      not survival in advanced non-small cell lung cancer.
AB  - BACKGROUND: A lot of studies have investigated the correlation between x-ray
      repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical
      outcomes in non-small cell cancer (NSCLC), while the conclusion is still
      conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate
      the predictive value of XRCC3 Thr241Met polymorphism on response and overall
      survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs)
      and corresponding 95% confidence intervals (95% CIs) were used to estimate the
      association strength. RESULTS: A total of 14 eligible studies with 2828 patients
      were identified according to our inclusion criteria. Meta-analysis results showed
      that carriers of the variant 241Met allele were significantly associated with
      good response, compared with those harboring the wild 241Thr allele (Met vs. Thr,
      OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs.
      ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696). This
      significant association was observed in Caucasian population but not in Asian
      population. On the other hand, there was no significant association of XRCC3
      Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95%
      CI: 0.929-1.261, Pheterogeneity = 0.564), and there was no difference between
      Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive
      role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy
      in patients with advanced NSCLC. Additionally, we first report that the XRCC3
      Thr241Met polymorphism is associated with response to platinum-based chemotherapy
      and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

PMID- 24116197
TI  - The allometry of coarse root biomass: log-transformed linear regression or
      nonlinear regression?
AB  - Precise estimation of root biomass is important for understanding carbon stocks
      and dynamics in forests. Traditionally, biomass estimates are based on allometric
      scaling relationships between stem diameter and coarse root biomass calculated
      using linear regression (LR) on log-transformed data. Recently, it has been
      suggested that nonlinear regression (NLR) is a preferable fitting method for
      scaling relationships. But while this claim has been contested on both
      theoretical and empirical grounds, and statistical methods have been developed to
      aid in choosing between the two methods in particular cases, few studies have
      examined the ramifications of erroneously applying NLR. Here, we use direct
      measurements of 159 trees belonging to three locally dominant species in east
      China to compare the LR and NLR models of diameter-root biomass allometry. We
      then contrast model predictions by estimating stand coarse root biomass based on
      census data from the nearby 24-ha Gutianshan forest plot and by testing the
      ability of the models to predict known root biomass values measured on multiple
      tropical species at the Pasoh Forest Reserve in Malaysia. Based on likelihood
      estimates for model error distributions, as well as the accuracy of extrapolative
      predictions, we find that LR on log-transformed data is superior to NLR for
      fitting diameter-root biomass scaling models. More importantly, inappropriately
      using NLR leads to grossly inaccurate stand biomass estimates, especially for
      stands dominated by smaller trees. 

PMID- 24116198
TI  - Entrainment of spontaneously hypertensive rat fibroblasts by temperature cycles.
AB  - The functional state of the circadian system of spontaneously hypertensive rats
      (SHR) differs in several characteristics from the functional state of
      normotensive Wistar rats. Some of these changes might be due to the compromised
      ability of the central pacemaker to entrain the peripheral clocks. Daily body
      temperature cycles represent one of the important cues responsible for the
      integrity of the circadian system, because these cycles are driven by the central
      pacemaker and are able to entrain the peripheral clocks. This study tested the
      hypothesis that the aberrant peripheral clock entrainment of SHR results from a
      compromised peripheral clock sensitivity to the daily temperature cycle
      resetting. Using cultured Wistar rat and SHR fibroblasts transfected with the
      circadian luminescence reporter Bmal1-dLuc, we demonstrated that two consecutive
      square-wave temperature cycles with amplitudes of 2.5  degrees C are necessary
      and sufficient to restart the dampened oscillations and entrain the circadian
      clocks in both Wistar rat and SHR fibroblasts. We also generated a phase response
      curve to temperature cycles for fibroblasts of both rat strains. Although some of
      the data suggested a slight resistance of SHR fibroblasts to temperature
      entrainment, we concluded that the overall effect it too weak to be responsible
      for the differences between the SHR and Wistar in vivo circadian phenotype.

PMID- 24116199
TI  - Time to tenure in Spanish universities: an event history analysis.
AB  - Understanding how institutional incentives and mechanisms for assigning
      recognition shape access to a permanent job is important. This study, based on
      data from questionnaire survey responses and publications of 1,257 university
      science, biomedical and engineering faculty in Spain, attempts to understand the
      timing of getting a permanent position and the relevant factors that account for
      this transition, in the context of dilemmas between mobility and permanence faced
      by organizations. Using event history analysis, the paper looks at the time to
      promotion and the effects of some relevant covariates associated to academic
      performance, social embeddedness and mobility. We find that research productivity
      contributes to career acceleration, but that other variables are also
      significantly associated to a faster transition. Factors associated to the social
      elements of academic life also play a role in reducing the time from PhD
      graduation to tenure. However, mobility significantly increases the duration of
      the non-tenure stage. In contrast with previous findings, the role of sex is
      minor. The variations in the length of time to promotion across different
      scientific domains is confirmed, with faster career advancement for those in the
      Engineering and Technological Sciences compared with academics in the Biological
      and Biomedical Sciences. Results show clear effects of seniority, and rewards to
      loyalty, in addition to some measurements of performance and quality of the
      university granting the PhD, as key elements speeding up career advancement.
      Findings suggest the existence of a system based on granting early permanent jobs
      to those that combine social embeddedness and team integration with some good
      credentials regarding past and potential future performance, rather than high
      levels of mobility. 

PMID- 24116200
TI  - An upstream YY1 binding site on the HIV-1 LTR contributes to latent infection.
AB  - During HIV-1 infection a population of latently infected cells is established.
      This population is the major obstacle preventing total eradication of the virus
      from AIDS patients. HIV-1 latency is thought to arise by various mechanisms
      including repressive chromatin modifications. Transcription factors such as YY1
      have been shown to facilitate repressive chromatin modifications by the
      recruitment of histone deacetylases. In this study, we identified a novel binding
      site for YY1 on the HIV-1 LTR, 120 nucleotides upstream of the transcription
      start site. We show that YY1 can bind to this site in vitro and in vivo and that
      binding to the LTR is dissociated upon T cell activation. Overexpression of YY1
      causes an increase in the proportion of cells that produce latent infections.
      These observations, in combination with previous results, demonstrate that YY1
      plays a prominent role in controlling the establishment and maintenance of latent
      HIV-1 provirus in unstimulated cells. 

PMID- 24116201
TI  - Portuguese migrants in Switzerland: healthcare and health status compared to
      Portuguese residents.
AB  - BACKGROUND: Most migrant studies have compared health characteristics between
      migrants and nationals of the host country. We aimed at comparing health
      characteristics of migrants with nationals from their home country. METHODS:
      Portuguese national health survey (2005-6; 30,173 participants aged 18-75 years)
      and four national health surveys conducted in Switzerland (2002, 2004, 2007 and
      2011, totalling 1,170 Portuguese migrants of the same age range). Self-reported
      data on length of stay, cardiovascular risk factors, healthcare use and health
      status were collected. RESULTS: Resident Portuguese were significantly older and
      more educated than migrants. Resident Portuguese had a higher mean BMI and
      prevalence of obesity than migrants. Resident Portuguese also reported more
      frequently being hypertensive and having their blood pressure screened within the
      last year. On the contrary, migrant Portuguese were more frequently smokers, had
      a medical visit in the previous year more frequently and self-rated their health
      higher than resident Portuguese. After adjustment for age, gender, marital status
      and education, migrants had a higher likelihood of smoking, of having a medical
      visit the previous year, and of self-rating their current health as good or very
      good than resident Portuguese. Compared to Portuguese residents, cholesterol
      screening in the previous year was more common only among migrants living in
      Switzerland for more than 17 years. CONCLUSION: Portuguese migrants in
      Switzerland do not differ substantially from resident Portuguese regarding most
      cardiovascular risk factors. Migrants consider themselves healthier than
      Portuguese residents and more often had a recent medical visit.

PMID- 24116202
TI  - Viral latency in blood and saliva of simian foamy virus-infected humans.
AB  - Simian foamy viruses (SFV) are widespread retroviruses among non-human primates
      (NHP). SFV actively replicate in the oral cavity and can be transmitted to humans
      through NHP bites, giving rise to a persistent infection. We aimed at studying
      the natural history of SFV infection in human. We have analyzed viral load and
      gene expression in 14 hunters from Cameroon previously shown to be infected with
      a gorilla SFV strain. Viral DNA could be detected by quantitative polymerase
      chain reaction (q-PCR) targeting the pol-in region, in most samples of peripheral
      blood mononuclear cells (PBMCs) (7.1 +/- 6.0 SFV DNA copies/105 PBMCs) and saliva
      (2.4 +/- 4.3 SFV DNA copies/105 cells) derived from the hunters. However,
      quantitative real-time reverse-transcription polymerase chain reaction (RT)-qPCR
      revealed the absence of SFV viral gene expression in both PBMCs and saliva,
      suggesting that SFV was latent in the human samples. Our study demonstrates that
      a latent infection can occur in humans and persist for years, both in PBMCs and
      saliva. Such a scenario may contribute to the putative lack of secondary human-to
      human transmissions of SFV. 

PMID- 24116203
TI  - Can DCE-MRI explain the heterogeneity in radiopeptide uptake imaged by SPECT in a
      pancreatic neuroendocrine tumor model?
AB  - Although efficient delivery and distribution of treatment agents over the whole
      tumor is essential for successful tumor treatment, the distribution of most of
      these agents cannot be visualized. However, with single-photon emission computed
      tomography (SPECT), both delivery and uptake of radiolabeled peptides can be
      visualized in a neuroendocrine tumor model overexpressing somatostatin receptors.
      A heterogeneous peptide uptake is often observed in these tumors. We hypothesized
      that peptide distribution in the tumor is spatially related to tumor perfusion,
      vessel density and permeability, as imaged and quantified by DCE-MRI in a
      neuroendocrine tumor model. Four subcutaneous CA20948 tumor-bearing Lewis rats
      were injected with the somatostatin-analog (111)In-DTPA-Octreotide (50 MBq).
      SPECT-CT and MRI scans were acquired and MRI was spatially registered to SPECT
      CT. DCE-MRI was analyzed using semi-quantitative and quantitative methods.
      Correlation between SPECT and DCE-MRI was investigated with 1) Spearman's rank
      correlation coefficient; 2) SPECT uptake values grouped into deciles with
      corresponding median DCE-MRI parametric values and vice versa; and 3) linear
      regression analysis for median parameter values in combined datasets. In all
      tumors, areas with low peptide uptake correlated with low perfusion/density/
      /permeability for all DCE-MRI-derived parameters. Combining all datasets, highest
      linear regression was found between peptide uptake and semi-quantitative
      parameters (R(2)>0.7). The average correlation coefficient between SPECT and DCE
      MRI-derived parameters ranged from 0.52-0.56 (p<0.05) for parameters primarily
      associated with exchange between blood and extracellular extravascular space. For
      these parameters a linear relation with peptide uptake was observed. In
      conclusion, the 'exchange-related' DCE-MRI-derived parameters seemed to predict
      peptide uptake better than the 'contrast amount- related' parameters.
      Consequently, fast and efficient diffusion through the vessel wall into tissue is
      an important factor for peptide delivery. DCE-MRI helps to elucidate the relation
      between vascular characteristics, peptide delivery and treatment efficacy, and
      may form a basis to predict targeting efficiency. 

PMID- 24116204
TI  - Assaying environmental nickel toxicity using model nematodes.
AB  - Although nickel exposure results in allergic reactions, respiratory conditions,
      and cancer in humans and rodents, the ramifications of excess nickel in the
      environment for animal and human health remain largely undescribed. Nickel and
      other cationic metals travel through waterways and bind to soils and sediments.
      To evaluate the potential toxic effects of nickel at environmental contaminant
      levels (8.9-7,600 ug Ni/g dry weight of sediment and 50-800 ug NiCl2/L of water),
      we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and
      Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous
      nickel upon animal growth, developmental survival, lifespan, and fecundity.
      Uncontaminated sediments were collected from sites in the Midwestern United
      States and spiked with a range of nickel concentrations. We found that nickel
      spiked sediment substantially impairs both survival from larval to adult stages
      and adult longevity in a concentration-dependent manner. Further, while aqueous
      nickel showed no adverse effects on either survivorship or longevity, we observed
      a significant decrease in fecundity, indicating that aqueous nickel could have a
      negative impact on nematode physiology. Intriguingly, C. elegans and P. pacificus
      exhibit similar, but not identical, responses to nickel exposure. Moreover, P.
      pacificus could be tested successfully in sediments inhospitable to C. elegans.
      Our results add to a growing body of literature documenting the impact of nickel
      on animal physiology, and suggest that environmental toxicological studies could
      gain an advantage by widening their repertoire of nematode species. 

PMID- 24116205
TI  - Strong evidence for a genetic contribution to late-onset Alzheimer's disease
      mortality: a population-based study.
AB  - BACKGROUND: Alzheimer's disease (AD) is an international health concern that has
      a devastating effect on patients and families. While several genetic risk factors
      for AD have been identified much of the genetic variance in AD remains
      unexplained. There are limited published assessments of the familiality of
      Alzheimer's disease. Here we present the largest genealogy-based analysis of AD
      to date. METHODS: We assessed the familiality of AD in The Utah Population
      Database (UPDB), a population-based resource linking electronic health data
      repositories for the state with the computerized genealogy of the Utah settlers
      and their descendants. We searched UPDB for significant familial clustering of AD
      to evaluate the genetic contribution to disease. We compared the Genealogical
      Index of Familiality (GIF) between AD individuals and randomly selected controls
      and estimated the Relative Risk (RR) for a range of family relationships.
      Finally, we identified pedigrees with a significant excess of AD deaths. RESULTS:
      The GIF analysis showed that pairs of individuals dying from AD were
      significantly more related than expected. This excess of relatedness was observed
      for both close and distant relationships. RRs for death from AD among relatives
      of individuals dying from AD were significantly increased for both close and more
      distant relatives. Multiple pedigrees had a significant excess of AD deaths.
      CONCLUSIONS: These data strongly support a genetic contribution to the observed
      clustering of individuals dying from AD. This report is the first large
      population-based assessment of the familiality of AD mortality and provides the
      only reported estimates of relative risk of AD mortality in extended relatives to
      date. The high-risk pedigrees identified show a true excess of AD mortality (not
      just multiple cases) and are greater in depth and width than published AD
      pedigrees. The presence of these high-risk pedigrees strongly supports the
      possibility of rare predisposition variants not yet identified.

PMID- 24116206
TI  - Diet-sensitive sources of reactive oxygen species in liver mitochondria: role of
      very long chain acyl-CoA dehydrogenases.
AB  - High fat diets and accompanying hepatic steatosis are highly prevalent
      conditions. Previous work has shown that steatosis is accompanied by enhanced
      generation of reactive oxygen species (ROS), which may mediate further liver
      damage. Here we investigated mechanisms leading to enhanced ROS generation
      following high fat diets (HFD). We found that mitochondria from HFD livers
      present no differences in maximal respiratory rates and coupling, but generate
      more ROS specifically when fatty acids are used as substrates. Indeed, many acyl
      CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers,
      although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more
      functionally active. Studies conducted with permeabilized mitochondria and
      different chain length acyl-CoA derivatives suggest that VLCAD is also a source
      of ROS production in mitochondria of HFD animals. This production is stimulated
      by the lack of NAD(+). Overall, our studies uncover VLCAD as a novel, diet
      sensitive, source of mitochondrial ROS. 

PMID- 24116207
TI  - A DNA-based semantic fusion model for remote sensing data.
AB  - Semantic technology plays a key role in various domains, from conversation
      understanding to algorithm analysis. As the most efficient semantic tool,
      ontology can represent, process and manage the widespread knowledge. Nowadays,
      many researchers use ontology to collect and organize data's semantic information
      in order to maximize research productivity. In this paper, we firstly describe
      our work on the development of a remote sensing data ontology, with a primary
      focus on semantic fusion-driven research for big data. Our ontology is made up of
      1,264 concepts and 2,030 semantic relationships. However, the growth of big data
      is straining the capacities of current semantic fusion and reasoning practices.
      Considering the massive parallelism of DNA strands, we propose a novel DNA-based
      semantic fusion model. In this model, a parallel strategy is developed to encode
      the semantic information in DNA for a large volume of remote sensing data. The
      semantic information is read in a parallel and bit-wise manner and an individual
      bit is converted to a base. By doing so, a considerable amount of conversion time
      can be saved, i.e., the cluster-based multi-processes program can reduce the
      conversion time from 81,536 seconds to 4,937 seconds for 4.34 GB source data
      files. Moreover, the size of result file recording DNA sequences is 54.51 GB for
      parallel C program compared with 57.89 GB for sequential Perl. This shows that
      our parallel method can also reduce the DNA synthesis cost. In addition, data
      types are encoded in our model, which is a basis for building type system in our
      future DNA computer. Finally, we describe theoretically an algorithm for DNA
      based semantic fusion. This algorithm enables the process of integration of the
      knowledge from disparate remote sensing data sources into a consistent, accurate,
      and complete representation. This process depends solely on ligation reaction and
      screening operations instead of the ontology. 

PMID- 24116208
TI  - From continental priorities to local conservation: a multi-level analysis for
      African tortoises.
AB  - Terrestrial tortoises are the most endangered group of vertebrates but they are
      still largely ignored for defining global conservation priorities. In this paper,
      we explored within a hierarchical framework the potential contribution of
      prioritization studies at the continental scale to the planning of local
      initiatives for the conservation of African tortoises at the regional level.
      First, we modeled the distribution of all the African tortoise species, we
      calculated three indicators of conservation priority (i.e., species richness,
      conservation value, and complementarity), and we carried out a gap analysis at
      continental scale. Second, we focused on the most important region for tortoise
      conservation and performed the same analyses at higher resolution. Finally, we
      compared the results from the two scales for understanding the degree to which
      they are complementary. Southern Africa emerged from the continental analysis as
      the most important region for tortoises. Within this area, the high-resolution
      analysis pointed out specific core sites for conservation. The relative degree of
      species protection was assessed similarly at the two different resolutions. Two
      species appeared particularly vulnerable at both scales. Priority indices
      calculated at high resolution were correlated to the values calculated for the
      corresponding cells at low resolution but the congruence was stronger for species
      richness. Our results suggest to integrate the calculation of conservation value
      and complementarity into a hierarchical framework driven by species richness. The
      advantages of large scale planning include its broad perspective on
      complementarity and the capability to identify regions with greatest conservation
      potential. In this light, continental analyses allow targeting fine scale studies
      toward regions with maximum priority. The regional analyses at fine scale allow
      planning conservation measure at a resolution similar to that required for the
      practical implementation, reducing the uncertainty associated with low resolution
      studies.

PMID- 24116209
TI  - Physician trainees' decision making and information processing: choice size and
      Medicare Part D.
AB  - Many patients expect their doctor to help them choose a Medicare prescription
      drug plan. Whether the size of the choice set affects clinicians' decision
      processes and strategy selection, and the quality of their choice, as it does
      their older patients, is an important question with serious financial
      consequences. Seventy medical students and internal medicine residents completed
      a within-subject design using Mouselab, a computer program that allows the
      information-acquisition process to be examined. We examined highly numerate
      physician trainees' decision processes, strategy, and their ability to pick the
      cheapest drug plan-as price was deemed the most important factor in Medicare
      beneficiaries' plan choice-from either 3 or 9 drug plans. Before adjustment,
      participants were significantly more likely to identify the lowest cost plan when
      facing three versus nine choices (67.3% vs. 32.8%, p<0.01) and paid significantly
      less in excess premiums ($60.00 vs. $128.51, p<0.01). Compared to the three-plan
      condition, in the nine-plan condition participants spent significantly less time
      acquiring information on each attribute (p<0.05) and were more likely to employ
      decision strategies focusing on comparing alternate plans across a single
      attribute (search pattern, p<0.05). After adjusting for decision process and
      strategy, numeracy, and amount of medical training, the odds were 10.75 times
      higher that trainees would choose the lowest cost Medicare Part D drug plan when
      facing 3 versus 9 drug plans (p<0.05). Although employing more efficient search
      strategies in the complex choice environment, physician trainees experienced
      similar difficulty in choosing the lowest cost prescription drug plans as older
      patients do. Our results add further evidence that simplifications to the
      Medicare Part D decision environment are needed and suggest physicians' role in
      their patients' Part D choices may be most productive when assisting seniors with
      forecasting their expected medication needs and then referring them to the
      Medicare website or helpline. 

PMID- 24116211
TI  - Host plant odors represent immiscible information entities - blend composition
      and concentration matter in hawkmoths.
AB  - Host plant choice is of vital importance for egg laying herbivorous insects that
      do not exhibit brood care. Several aspects, including palatability, nutritional
      quality and predation risk, have been found to modulate host preference.
      Olfactory cues are thought to enable host location. However, experimental data on
      odor features that allow choosing among alternative hosts while still in flight
      are not available. It has previously been shown that M. sexta females prefer
      Datura wrightii compared to Nicotiana attenuata. The bouquet of the latter is
      more intense and contains compounds typically emitted by plants after feeding
      damage to attract the herbivore's enemies. In this wind tunnel study, we offered
      female gravid hawkmoths (Manduca sexta) odors from these two ecologically
      relevant, attractive, non-flowering host species. M. sexta females preferred
      surrogate leaves scented with vegetative odors form both host species to
      unscented control leaves. Given a choice between species, females preferred the
      odor bouquet emitted by D. wrightii to that of N. attenuata. Harmonizing, i.e.
      adjusting, volatile intensity to similar levels did not abolish but significantly
      weakened this preference. Superimposing, i.e. mixing, the highly attractive
      headspaces of both species, however, abolished discrimination between scented and
      non-scented surrogate leaves. Beyond ascertaining the role of blend composition
      in host plant choice, our results raise the following hypotheses. (i) The odor of
      a host species is perceived as a discrete odor 'Gestalt', and its core properties
      are lost upon mixing two attractive scents (ii). Stimulus intensity is a
      secondary feature affecting olfactory-based host choice (iii). Constitutively
      smelling like a plant that is attracting herbivore enemies may be part of a
      plant's strategy to avoid herbivory where alternative hosts are available to the
      herbivore. 

PMID- 24116210
TI  - An anti-CD34 antibody-functionalized clinical-grade POSS-PCU nanocomposite
      polymer for cardiovascular stent coating applications: a preliminary assessment
      of endothelial progenitor cell capture and hemocompatibility.
AB  - In situ endothelialization of cardiovascular implants has emerged in recent years
      as an attractive means of targeting the persistent problems of thrombosis and
      intimal hyperplasia. This study aimed to investigate the efficacy of immobilizing
      anti-CD34 antibodies onto a POSS-PCU nanocomposite polymer surface to sequester
      endothelial progenitor cells (EPCs) from human blood, and to characterize the
      surface properties and hemocompatibility of this surface. Amine-functionalized
      fumed silica was used to covalently conjugate anti-CD34 to the polymer surface.
      Water contact angle, fluorescence microscopy, and scanning electron microscopy
      were used for surface characterization. Peripheral blood mononuclear cells
      (PBMCs) were seeded on modified and pristine POSS-PCU polymer films. After 7
      days, adhered cells were immunostained for the expression of EPC and endothelial
      cell markers, and assessed for the formation of EPC colonies. Hemocompatibility
      was assessed by thromboelastography, and platelet activation and adhesion assays.
      The number of EPC colonies formed on anti-CD34-coated POSS-PCU surfaces was not
      significantly higher than that of POSS-PCU (5.0+/-1.0 vs. 1.7+/-0.6, p>0.05).
      However, antibody conjugation significantly improved hemocompatibility, as seen
      from the prolonged reaction and clotting times, decreased angle and maximum
      amplitude (p<0.05), as well as decreased platelet adhesion (76.8+/-7.8 vs. 8.4+/
      0.7, p<0.05) and activation. Here, we demonstrate that POSS-PCU surface
      immobilized anti-CD34 antibodies selectively captured CD34+ cells from peripheral
      blood, although only a minority of these were EPCs. Nevertheless, antibody
      conjugation significantly improves the hemocompatibility of POSS-PCU, and should
      therefore continue to be explored in combination with other strategies to improve
      the specificity of EPC capture to promote in situ endothelialization.

PMID- 24116212
TI  - In vitro grown pollen tubes of Nicotiana alata actively synthesise a fucosylated
      xyloglucan.
AB  - Nicotiana alata pollen tubes are a widely used model for studies of polarized tip
      growth and cell wall synthesis in plants. To better understand these processes,
      RNA-Seq and de novo assembly methods were used to produce a transcriptome of N.
      alata pollen grains. Notable in the reconstructed transcriptome were sequences
      encoding proteins that are involved in the synthesis and remodelling of
      xyloglucan, a cell wall polysaccharide previously not thought to be deposited in
      Nicotiana pollen tube walls. Expression of several xyloglucan-related genes in
      actively growing pollen tubes was confirmed and xyloglucan epitopes were detected
      in the wall with carbohydrate-specific antibodies: the major xyloglucan
      oligosaccharides found in N. alata pollen grains and tubes were fucosylated, an
      unusual structure for the Solanaceae, the family to which Nicotiana belongs.
      Finally, carbohydrate linkages consistent with xyloglucan were identified
      chemically in the walls of N. alata pollen grains and pollen tubes grown in
      culture. The presence of a fucosylated xyloglucan in Nicotiana pollen tube walls
      was thus confirmed. The consequences of this discovery to models of pollen tube
      growth dynamics and more generally to polarised tip-growing cells in plants are
      discussed. 

PMID- 24116213
TI  - The fumagillin gene cluster, an example of hundreds of genes under veA control in
      Aspergillus fumigatus.
AB  - Aspergillus fumigatus is the causative agent of invasive aspergillosis, leading
      to infection-related mortality in immunocompromised patients. We previously
      showed that the conserved and unique-to-fungi veA gene affects different cell
      processes such as morphological development, gliotoxin biosynthesis and protease
      activity, suggesting a global regulatory effect on the genome of this medically
      relevant fungus. In this study, RNA sequencing analysis revealed that veA
      controls the expression of hundreds of genes in A. fumigatus, including those
      comprising more than a dozen known secondary metabolite gene clusters. Chemical
      analysis confirmed that veA controls the synthesis of other secondary metabolites
      in this organism in addition to gliotoxin. Among the secondary metabolite gene
      clusters regulated by veA is the elusive but recently identified gene cluster
      responsible for the biosynthesis of fumagillin, a meroterpenoid known for its
      anti-angiogenic activity by binding to human methionine aminopeptidase 2. The
      fumagillin gene cluster contains a veA-dependent regulatory gene, fumR
      (Afu8g00420), encoding a putative C6 type transcription factor. Deletion of fumR
      results in silencing of the gene cluster and elimination of fumagillin
      biosynthesis. We found expression of fumR to also be dependent on laeA, a gene
      encoding another component of the fungal velvet complex. The results in this
      study argue that veA is a global regulator of secondary metabolism in A.
      fumigatus, and that veA may be a conduit via which chemical development is
      coupled to morphological development and other cellular processes. 

PMID- 24116214
TI  - Excess winter mortality and cold temperatures in a subtropical city, Guangzhou,
      China.
AB  - BACKGROUND: A significant increase in mortality was observed during cold winters
      in many temperate regions. However, there is a lack of evidence from tropical and
      subtropical regions, and the influence of ambient temperatures on seasonal
      variation of mortality was not well documented. METHODS: This study included
      213,737 registered deaths from January 2003 to December 2011 in Guangzhou, a
      subtropical city in Southern China. Excess winter mortality was calculated by the
      excess percentage of monthly mortality in winters over that of non-winter months.
      A generalized linear model with a quasi-Poisson distribution was applied to
      analyze the association between monthly mean temperature and mortality, after
      controlling for other meteorological measures and air pollution. RESULTS: The
      mortality rate in the winter was 26% higher than the average rate in other
      seasons. On average, there were 1,848 excess winter deaths annually, with around
      half (52%) from cardiovascular diseases and a quarter (24%) from respiratory
      diseases. Excess winter mortality was higher in the elderly, females and those
      with low education level than the young, males and those with high education
      level, respectively. A much larger winter increase was observed in out-of
      hospital mortality compared to in-hospital mortality (45% vs. 17%). We found a
      significant negative correlation of annual excess winter mortality with average
      winter temperature (rs=-0.738, P=0.037), but not with air pollution levels. A 1 
      degrees C decrease in monthly mean temperature was associated with an increase of
      1.38% (95% CI:0.34%-2.40%) and 0.88% (95% CI:0.11%-1.64%) in monthly mortality at
      lags of 0-1 month, respectively. CONCLUSION: Similar to temperate regions, a
      subtropical city Guangzhou showed a clear seasonal pattern in mortality, with a
      sharper spike in winter. Our results highlight the role of cold temperature on
      the winter mortality even in warm climate. Precautionary measures should be
      strengthened to mitigate cold-related mortality for people living in warm
      climate.

PMID- 24116215
TI  - Escherichia coli producing colibactin triggers premature and transmissible
      senescence in mammalian cells.
AB  - Cellular senescence is an irreversible state of proliferation arrest evoked by a
      myriad of stresses including oncogene activation, telomere shortening/dysfunction
      and genotoxic insults. It has been associated with tumor activation, immune
      suppression and aging, owing to the secretion of proinflammatory mediators. The
      bacterial genotoxin colibactin, encoded by the pks genomic island is frequently
      harboured by Escherichia coli strains of the B2 phylogenetic group. Mammalian
      cells exposed to live pks+ bacteria exhibit DNA-double strand breaks (DSB) and
      undergo cell-cycle arrest and death. Here we show that cells that survive the
      acute bacterial infection with pks+ E. coli display hallmarks of cellular
      senescence: chronic DSB, prolonged cell-cycle arrest, enhanced senescence
      associated beta-galactosidase (SA-beta-Gal) activity, expansion of promyelocytic
      leukemia nuclear foci and senescence-associated heterochromatin foci. This was
      accompanied by reactive oxygen species production and pro-inflammatory cytokines,
      chemokines and proteases secretion. These mediators were able to trigger DSB and
      enhanced SA-beta-Gal activity in bystander recipient cells treated with
      conditioned medium from senescent cells. Furthermore, these senescent cells
      promoted the growth of human tumor cells. In conclusion, the present data
      demonstrated that the E. coli genotoxin colibactin induces cellular senescence
      and subsequently propel bystander genotoxic and oncogenic effects. 

PMID- 24116216
TI  - Relationship between cerebrospinal fluid biomarkers for inflammation,
      demyelination and neurodegeneration in acute optic neuritis.
AB  - BACKGROUND: Various inflammatory biomarkers show prognostic potential for
      multiple sclerosis (MS)-risk after clinically isolated syndromes. However,
      biomarkers are often examined singly and their interrelation and precise aspects
      of their associated pathological processes remain unclear. Clarification of these
      relationships could aid the appropriate implementation of prognostic biomarkers
      in clinical practice. OBJECTIVE: To investigate the interrelation between
      biomarkers of inflammation, demyelination and neurodegeneration in acute optic
      neuritis and to assess their association to measures of MS risk. MATERIAL AND
      METHODS: A prospective study at a tertiary referral centre from June 2011 to
      December 2012 of 56 patients with optic neuritis as a first demyelinating symptom
      and 27 healthy volunteers. Lumbar puncture was performed within 28 (median 16)
      days of onset. CSF levels of CXCL13, matrix metalloproteinase (MMP)-9, CXCL10,
      CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein (MBP) and
      neurofilament light-chain (NF-L) were determined. MS-risk outcome measures were
      dissemination in space (DIS) of white matter lesions on cerebral MRI, CSF
      oligoclonal bands and elevated IgG-index. RESULTS: IN THE INTERRELATION ANALYSIS
      THE BIOMARKERS SHOWED CLOSE CORRELATIONS WITHIN TWO DISTINCT GROUPS: Biomarkers
      of leukocyte infiltration (CXCL13, MMP-9 and CXCL10) were strongly associated
      (p<0.0001 for all). Osteopontin and chitinase-3-like-1 were also tightly
      associated (p<0.0001) and correlated strongly to tissue damage markers (NF-L and
      MBP). The biomarkers of leukocyte infiltration all associated strongly with MS
      risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF
      MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk
      parameters. CONCLUSIONS: OUR FINDINGS SUGGEST TWO DISTINCT INFLAMMATORY
      PROCESSES: one of leukocyte infiltration, represented by CXCL13, CXCL10 and MMP
      9, strongly associated with and potentially predicting MS-risk; the other
      represented by osteopontin and CHI3L1, suggesting tissue damage-related
      inflammation, potentially predicting residual disabilities after attack and
      perhaps cumulative damage over time. These hypotheses should be further addressed
      in follow-up studies.

PMID- 24116217
TI  - Mitochondrial aminopeptidase deletion increases chronological lifespan and
      oxidative stress resistance while decreasing respiratory metabolism in S.
      cerevisiae.
AB  - Recessive mutations in XPNPEP3, encoding a mitochondrial x-prolyl aminopeptidase,
      have been identified in families with a rare hereditary tubulointerstitial kidney
      disease. The yeast ortholog of XPNPEP3, Icp55p, participates in the proteolytic
      processing and stabilization of mitochondrial proteins and its deletion
      accelerates the degradation of its protein targets. We used icp55 deletion
      strains of S. cerevisiae to model loss of XPNPEP3 enzymatic function and study
      its phenotypic consequences on mitochondrial function. We found that Icp55p is
      not required for respiratory competence; however, compared to controls deletion
      strains had reduced mitochondrial oxygen consumption when grown in glucose
      containing media. The reduced mitochondrial respiration of icp55 deletion strains
      in glucose media requires the mitochondrial peptide transporter, Mdl1p, and was
      corrected by Tor1p inhibition with rapamycin. Under similar growth conditions the
      abundance of the mitochondrial ATP synthase complex was decreased in the icp55
      deletion strain and was corrected by concurrent deletion of tor1. The icp55
      deletion strain demonstrated an increased chronological lifespan and decreased
      reactive oxygen species. These changes were additive to similar changes known to
      occur in tor1 deletion strains suggesting independent mechanisms. Together, these
      results demonstrate that loss of Icp55p function reduces mitochondrial oxygen
      consumption and ATP synthase complex assembly in glucose media, while also
      promoting stress resistance, decreasing reactive oxygen species and increasing
      chronological lifespan through mechanisms that are distinct from decreased Tor1p
      activity. 

PMID- 24116218
TI  - Regulation of myosin light chain kinase during insulin-stimulated glucose uptake
      in 3T3-L1 adipocytes.
AB  - Myosin II (MyoII) is required for insulin-responsive glucose transporter 4
      (GLUT4)-mediated glucose uptake in 3T3-L1 adipocytes. Our previous studies have
      shown that insulin signaling stimulates phosphorylation of the regulatory light
      chain (RLC) of MyoIIA via myosin light chain kinase (MLCK). The experiments
      described here delineate upstream regulators of MLCK during insulin-stimulated
      glucose uptake. Since 3T3-L1 adipocytes express two MyoII isoforms, we wanted to
      determine which isoform was required for insulin-stimulated glucose uptake. Using
      a siRNA approach, we demonstrate that a 60% decrease in MyoIIA protein expression
      resulted in a 40% inhibition of insulin-stimulated glucose uptake. We also show
      that insulin signaling stimulates the phosphorylation of MLCK. We further show
      that MLCK can be activated by calcium as well as signaling pathways. We
      demonstrate that adipocytes treated with the calcium chelating agent, 1,2-b (iso
      aminophenoxy) ethane-N,N,N',N'-tetra acetic acid, (BAPTA) (in the presence of
      insulin) impaired the insulin-induced phosphorylation of MLCK by 52% and the RLC
      of MyoIIA by 45% as well as impairing the recruitment of MyoIIA to the plasma
      membrane when compared to cells treated with insulin alone. We further show that
      the calcium ionophore, A23187 alone stimulated the phosphorylation of MLCK and
      the RLC associated with MyoIIA to the same extent as insulin. To identify
      signaling pathways that might regulate MLCK, we examined ERK and CaMKII.
      Inhibition of ERK2 impaired phosphorylation of MLCK and insulin-stimulated
      glucose uptake. In contrast, while inhibition of CaMKII did inhibit
      phosphorylation of the RLC associated with MyoIIA, inhibition of CAMKIIdelta did
      not impair MLCK phosphorylation or translocation to the plasma membrane or
      glucose uptake. Collectively, our results are the first to delineate a role for
      calcium and ERK in the activation of MLCK and thus MyoIIA during insulin
      stimulated glucose uptake in 3T3-L1 adipocytes. 

PMID- 24116219
TI  - Are characiform fishes Gondwanan in origin? Insights from a time-scaled molecular
      phylogeny of the Citharinoidei (Ostariophysi: Characiformes).
AB  - Fishes of the order Characiformes are a diverse and economically important
      teleost clade whose extant members are found exclusively in African and
      Neotropical freshwaters. Although their transatlantic distribution has been
      primarily attributed to the Early Cretaceous fragmentation of western Gondwana,
      vicariance has not been tested with temporal information beyond that contained in
      their fragmentary fossil record and a recent time-scaled phylogeny focused on the
      African family Alestidae. Because members of the suborder Citharinoidei
      constitute the sister lineage to the entire remaining Afro-Neotropical
      characiform radiation, we inferred a time-calibrated molecular phylogeny of
      citharinoids using a popular Bayesian approach to molecular dating in order to
      assess the adequacy of current vicariance hypotheses and shed light on the early
      biogeographic history of characiform fishes. Given that the only comprehensive
      phylogenetic treatment of the Citharinoidei has been a morphology-based analysis
      published over three decades ago, the present study also provided an opportunity
      to further investigate citharinoid relationships and update the evolutionary
      framework that has laid the foundations for the current classification of the
      group. The inferred chronogram is robust to changes in calibration priors and
      suggests that the origins of citharinoids date back to the Turonian (ca 90 Ma) of
      the Late Cretaceous. Most modern citharinoid genera, however, appear to have
      originated and diversified much more recently, mainly during the Miocene. By
      reconciling molecular-clock- with fossil-based estimates for the origins of the
      Characiformes, our results provide further support for the hypothesis that
      attributes the disjunct distribution of the order to the opening of the South
      Atlantic Ocean. The striking overlap in tempo of diversification and
      biogeographic patterns between citharinoids and the African-endemic family
      Alestidae suggests that their evolutionary histories could have been strongly and
      similarly influenced by Miocene geotectonic events that modified the landscape
      and produced the drainage pattern of Central Africa seen today. 

PMID- 24116220
TI  - Deletion genotypes reduce occlusion body potency but increase occlusion body
      production in a Colombian Spodoptera frugiperda nucleopolyhedrovirus population.
AB  - A Colombian field isolate (SfCOL-wt) of Spodoptera frugiperda multiple
      nucleopolyhedrovirus (SfMNPV) is a mixture of different genotypes. To evaluate
      the insecticidal properties of the different genotypic variants, 83 plaque
      purified virus were characterized. Ten distinct genotypes were identified (named
      A through J). SfCOL-A was the most prevalent (71+/-2%; mean +/- SE) showing a
      PstI restriction profile indistinguishable to that of SfCOL-wt. The remaining
      nine genotypes presented genomic deletions of 3.8 - 21.8 Kb located mainly
      between nucleotides 11,436 and 33,883 in the reference genome SfMNPV-B, affecting
      the region between open reading frames (ORFs) sf20 and sf33. The insecticidal
      activity of each genotype from SfCOL-wt and several mixtures of genotypes was
      compared to that of SfCOL-wt. The potency of SfCOL-A occlusion bodies (OBs) was
      4.4-fold higher than SfCOL-wt OBs, whereas the speed of kill of SfCOL-A was
      similar to that of SfCOL-wt. Deletion genotype OBs were similarly or less potent
      than SfCOL-wt but six deletion genotypes were faster killing than SfCOL-wt. The
      potency of genotype mixtures co-occluded within OBs were consistently reduced in
      two-genotype mixtures involving equal proportions of SfCOL-A and one of three
      deletion genotypes (SfCOL-C, -D or -F). Speed of kill and OB production were
      improved only when the certain genotype mixtures were co-occluded, although OB
      production was higher in the SfCOL-wt isolate than in any of the component
      genotypes, or mixtures thereof. Deleted genotypes reduced OB potency but
      increased OB production of the SfCOL-wt population, which is structured to
      maximize the production of OBs in each infected host. 

PMID- 24116221
TI  - Rapid inhibition of pyruvate dehydrogenase: an initiating event in high dietary
      fat-induced loss of metabolic flexibility in the heart.
AB  - Cardiac function depends on the ability to switch between fatty acid and glucose
      oxidation for energy production in response to changes in substrate availability
      and energetic stress. In obese and diabetic individuals, increased reliance on
      fatty acids and reduced metabolic flexibility are thought to contribute to the
      development of cardiovascular disease. Mechanisms by which cardiac mitochondria
      contribute to diet-induced metabolic inflexibility were investigated. Mice were
      fed a high fat or low fat diet for 1 d, 1 wk, and 20 wk. Cardiac mitochondria
      isolated from mice fed a high fat diet displayed a diminished ability to utilize
      the glycolytically derived substrate pyruvate. This response was rapid, occurring
      within the first day on the diet, and persisted for up to 20 wk. A selective
      increase in the expression of pyruvate dehydrogenase kinase 4 and inhibition of
      pyruvate dehydrogenase are responsible for the rapid suppression of pyruvate
      utilization. An important consequence is that pyruvate dehydrogenase is
      sensitized to inhibition when mitochondria respire in the presence of fatty
      acids. Additionally, increased expression of pyruvate dehydrogenase kinase 4
      preceded any observed diet-induced reductions in the levels of glucose
      transporter type 4 and glycolytic enzymes and, as judged by Akt phosphorylation,
      insulin signaling. Importantly, diminished insulin signaling evident at 1 wk on
      the high fat diet did not occur in pyruvate dehydrogenase kinase 4 knockout mice.
      Dietary intervention leads to a rapid decline in pyruvate dehydrogenase kinase 4
      levels and recovery of pyruvate dehydrogenase activity indicating an additional
      form of regulation. Finally, an overnight fast elicits a metabolic response
      similar to that induced by high dietary fat obscuring diet-induced metabolic
      changes. Thus, our data indicate that diet-induced inhibition of pyruvate
      dehydrogenase may be an initiating event in decreased oxidation of glucose and
      increased reliance of the heart on fatty acids for energy production. 

PMID- 24116222
TI  - Chafuroside B, an Oolong tea polyphenol, ameliorates UVB-induced DNA damage and
      generation of photo-immunosuppression related mediators in human keratinocytes.
AB  - Chafuroside B was recently isolated as a new polyphenolic constituent of oolong
      tea leaves. However, the effects of chafuroside B on skin function have not been
      examined. In this study, we investigated the protective effects of chafuroside B
      against UVB-induced DNA damage, apoptosis and generation of photo
      immunosuppression related mediators in cultured normal human epidermal
      keratinocytes (NHEK). Chafuroside B at 1 uM attenuated both UVB-induced
      apoptosis, evaluated in terms of caspase-3/7 activity, and UVB-induced DNA
      damage, evaluated in terms of formation of cyclobutane pyrimidine dimers (CPD),
      in NHEK exposed to UVB (20 mJ/cm2). In addition, chafuroside B at 0.3 or 1 uM
      suppressed the UVB-induced production of interleukin (IL)-10, tumor necrosis
      factor (TNF)-alpha, and prostaglandin E2 (PGE2), as determined by ELISA, and
      conversely enhanced IL-12 mRNA expression and production, as measured by RT-PCR
      and ELISA. Further, chafuroside B at 1 uM also suppressed UVB-induced expression
      of receptor activator of nuclear factor kappaB ligand (RANKL) mRNA. These results
      indicate that chafuroside B promotes repair of UVB-induced DNA damage and
      ameliorates the generation of IL-10, TNF-alpha, PGE2, and RANKL, all of which are
      UVB-induced immunosuppression related mediators. These effects of chafuroside B
      may be mediated at least in part through induction of IL-12 synthesis in human
      keratinocytes. Because chafuroside B might have practical value as a
      photoprotective agent, a further study of the in vivo effects of chafuroside B
      seems warranted.

PMID- 24116223
TI  - Regional fibronectin and collagen fibril co-assembly directs cell proliferation
      and microtissue morphology.
AB  - The extracellular matrix protein, fibronectin stimulates cells to self-assemble
      into three-dimensional multicellular structures by a mechanism that requires the
      cell-dependent conversion of soluble fibronectin molecules into insoluble
      fibrils. Fibronectin also binds to collagen type I and mediates the co-assembly
      of collagen fibrils into the extracellular matrix. Here, the role of collagen
      fibronectin binding in fibronectin-induced cellular self-assembly was
      investigated using fibronectin-null fibroblasts in an in vitro model of tissue
      formation. High resolution, two-photon immunofluorescence microscopy was combined
      with second harmonic generation imaging to examine spatial and temporal
      relationships among fibronectin and collagen fibrils, actin organization, cell
      proliferation, and microtissue morphology. Time course studies coupled with
      simultaneous 4-channel multiphoton imaging identified regional differences in
      fibronectin fibril conformation, collagen fibril remodeling, actin organization,
      and cell proliferation during three-dimensional cellular self-assembly. Regional
      differences in cell proliferation and fibronectin structure were dependent on
      both soluble fibronectin concentration and fibronectin-collagen interactions.
      Fibronectin-collagen binding was not necessary for either fibronectin matrix
      formation or intercellular cohesion. However, inhibiting fibronectin binding to
      collagen reduced collagen fibril remodeling, decreased fibronectin fibril
      extension, blocked fibronectin-induced cell proliferation, and altered
      microtissue morphology. Furthermore, continual fibronectin-collagen binding was
      necessary to maintain both cell proliferation and microtissue morphology.
      Collectively, these data suggest that the complex changes in extracellular matrix
      and cytoskeletal remodeling that mediate tissue assembly are driven, in part, by
      regional variations in cell-mediated fibronectin-collagen co-assembly. 

PMID- 24116225
TI  - The taxonomy and phylogeny of Echinometra (Camarodonta: Echinometridae) from the
      red sea and western Indian Ocean.
AB  - The number of valid species in the genus Echinometra (Echinodermata, Echinoidea)
      and their associated identification keys have been debated in the scientific
      literature for more than 180 years. As the phylogeny and dispersal patterns of
      these species have been widely used as a prominent model for marine speciation,
      new insights into their taxonomy have the potential to deepen our understanding
      of marine speciation processes. In this study we examine Echinometra taxonomy,
      combining morphology and molecular tools. We present the taxonomy and phylogeny
      of Red Sea and western Indian Ocean Echinometra. The currently available
      morphological keys were found to be limited in their ability to delineate all
      species within this genus. Nonetheless, morphological similarities between the
      Red Sea and western Indian Ocean populations were high, and delimited them from
      the other species. These latter populations together formed a monophyletic clade,
      genetically distant from any of the other Echinometra species by more than 3%.
      Combining both traditional taxonomy and molecular evidence, we found that these
      populations were neither Echinometra mathaei nor E. oblonga, as previously
      considered. The morphological discrepancies of these populations, and their
      genetic divergence from the other Echinometra species, suggest that they should
      be considered as a new Echinometra species.

PMID- 24116224
TI  - HIV-1 Vpr induces the degradation of ZIP and sZIP, adaptors of the NuRD chromatin
      remodeling complex, by hijacking DCAF1/VprBP.
AB  - The Vpr protein from type 1 and type 2 Human Immunodeficiency Viruses (HIV-1 and
      HIV-2) is thought to inactivate several host proteins through the hijacking of
      the DCAF1 adaptor of the Cul4A ubiquitin ligase. Here, we identified two
      transcriptional regulators, ZIP and sZIP, as Vpr-binding proteins degraded in the
      presence of Vpr. ZIP and sZIP have been shown to act through the recruitment of
      the NuRD chromatin remodeling complex. Strikingly, chromatin is the only cellular
      fraction where Vpr is present together with Cul4A ubiquitin ligase subunits.
      Components of the NuRD complex and exogenous ZIP and sZIP were also associated
      with this fraction. Several lines of evidence indicate that Vpr induces ZIP and
      sZIP degradation by hijacking DCAF1: (i) Vpr induced a drastic decrease of
      exogenously expressed ZIP and sZIP in a dose-dependent manner, (ii) this decrease
      relied on the proteasome activity, (iii) ZIP or sZIP degradation was impaired in
      the presence of a DCAF1-binding deficient Vpr mutant or when DCAF1 expression was
      silenced. Vpr-mediated ZIP and sZIP degradation did not correlate with the growth
      related Vpr activities, namely G2 arrest and G2 arrest-independent cytotoxicity.
      Nonetheless, infection with HIV-1 viruses expressing Vpr led to the degradation
      of the two proteins. Altogether our results highlight the existence of two host
      transcription factors inactivated by Vpr. The role of Vpr-mediated ZIP and sZIP
      degradation in the HIV-1 replication cycle remains to be deciphered. 

PMID- 24116226
TI  - Effects of emotional context on memory for details: the role of attention.
AB  - It was repeatedly demonstrated that a negative emotional context enhances memory
      for central details while impairing memory for peripheral information. This trade
      off effect is assumed to result from attentional processes: a negative context
      seems to narrow attention to central information at the expense of more
      peripheral details, thus causing the differential effects in memory. However,
      this explanation has rarely been tested and previous findings were partly
      inconclusive. For the present experiment 13 negative and 13 neutral naturalistic,
      thematically driven picture stories were constructed to test the trade-off effect
      in an ecologically more valid setting as compared to previous studies. During an
      incidental encoding phase, eye movements were recorded as an index of overt
      attention. In a subsequent recognition phase, memory for central and peripheral
      details occurring in the picture stories was tested. Explicit affective ratings
      and autonomic responses validated the induction of emotion during encoding.
      Consistent with the emotional trade-off effect on memory, encoding context
      differentially affected recognition of central and peripheral details. However,
      contrary to the common assumption, the emotional trade-off effect on memory was
      not mediated by attentional processes. By contrast, results suggest that the
      relevance of attentional processing for later recognition memory depends on the
      centrality of information and the emotional context but not their interaction.
      Thus, central information was remembered well even when fixated very briefly
      whereas memory for peripheral information depended more on overt attention at
      encoding. Moreover, the influence of overt attention on memory for central and
      peripheral details seems to be much lower for an arousing as compared to a
      neutral context. 

PMID- 24116227
TI  - Infection of Burkholderia cepacia induces homeostatic responses in the host for
      their prolonged survival: the microarray perspective.
AB  - Burkholderia cepacia is an opportunistic human pathogen associated with life
      threatening pulmonary infections in immunocompromised individuals. Pathogenesis
      of B. cepacia infection involves adherence, colonisation, invasion, survival and
      persistence in the host. In addition, B. cepacia are also known to secrete
      factors, which are associated with virulence in the pathogenesis of the
      infection. In this study, the host factor that may be the cause of the infection
      was elucidated in human epithelial cell line, A549, that was exposed to live B.
      cepacia (mid-log phase) and its secretory proteins (mid-log and early-stationary
      phases) using the Illumina Human Ref-8 microarray platform. The non-infection
      A549 cells were used as a control. Expression of the host genes that are related
      to apoptosis, inflammation and cell cycle as well as metabolic pathways were
      differentially regulated during the infection. Apoptosis of the host cells and
      secretion of pro-inflammatory cytokines were found to be inhibited by both live
      B. cepacia and its secretory proteins. In contrast, the host cell cycle and
      metabolic processes, particularly glycolysis/glycogenesis and fatty acid
      metabolism were transcriptionally up-regulated during the infection. Our
      microarray analysis provided preliminary insights into mechanisms of B. cepacia
      pathogenesis. The understanding of host response to an infection would provide
      novel therapeutic targets both for enhancing the host's defences and repressing
      detrimental responses induced by the invading pathogen. 

PMID- 24116228
TI  - Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte
      transendothelial migration.
AB  - Lymphocyte trafficking and migration through vascular endothelial cells (ECs) in
      secondary lymphoid tissues is critical for immune protection. In the present
      study, we investigate the role of nectin cell adhesion molecules for the
      migration of lymphocytes through ECs. Nectins are key players for the
      establishment of homotypic and heterotypic cell to cell contacts; they are
      required for cell to cell adherens junction formation and take part in the
      transendothelial migration of monocytes during the step of diapedesis, when
      monocytes migrate through EC junctions. We first show that Nectin-3 (CD113) is
      the only nectin expressed by T lymphocytes and since nectins are expressed on ECs
      we explored Nectin-3 potential functions in lymphocyte: EC interactions. We
      demonstrate that Nectin-2, expressed on ECs, is the major counter-receptor of
      Nectin-3. A soluble form of Nectin-3 binds to Nectin-2 localized at EC junctions
      and blocking Nectin-2 trans-interactions with monoclonal antibodies abolishes the
      binding of soluble Nectin-3 to ECs. Nectin-2 is expressed on High Endothelial
      venules (HEVs), where lymphocyte homing occurs in vivo. Finally, we show that
      Nectin-3 trans-interaction with Nectin-2 is essential for the process of
      lymphocyte transendothelial migration in vitro as targeting with blocking
      monoclonal antibodies either Nectin-3, expressed on lymphocytes, or Nectin-2,
      expressed on ECs, inhibits lymphocyte extravasation. The nectin family of CAMs is
      important for the regulation of endothelial barrier functions and
      transendothelial migration of immune cells. Our results demonstrate for the first
      time that Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and
      monocyte extravasation. 

PMID- 24116230
TI  - Paternal age and general cognitive ability-a cross sectional study of Danish male
      conscripts.
AB  - OBJECTIVES: Offspring of older men have impaired cognitive ability as children,
      but it is unclear if this impairment persists into adulthood. The main objective
      of this study was to explore the association between paternal age at offspring
      birth and general cognitive ability as young adults. DESIGN: Population-based
      cross-sectional study with prospectively collected data on obstetric factors and
      parental education. SETTING: Nationwide Danish sample. PARTICIPANTS: Male
      conscripts (n = 169,009). PRIMARY AND SECONDARY OUTCOME MEASURES: General
      cognitive ability as assessed by the Borge Priens test score, an intelligence
      test with components related to logical, verbal, numerical and spatial reasoning.
      RESULTS: We observed an inverse U-shaped association between paternal age and
      general cognitive ability (slightly lower test scores in the offspring of fathers
      aged less than 25 years and older than 40 years, compared with fathers aged 25 to
      29 years). However, after adjustment for maternal age, parental education and
      birth order the shape of the association changed. Offspring of fathers younger
      than 20 still showed slightly lower cognitive ability (-1.11 (95% CI -1.68 to 
      0.54)), but no significant impairments were identified in the men whose fathers
      were older than 29 years at the time of their birth (e.g. the mean difference in
      test score in the offspring of fathers aged 40 to 44 years were -0.03 [95% CI (
      0.27 to 0.20)] compared with fathers aged 25 to 29 years). CONCLUSIONS: We did
      not find that the offspring of older fathers had impaired cognitive ability as
      young adults. Whereas, we found a tendency that the offspring of teen fathers
      have lower cognitive ability. Thus, our results suggest that any potentially
      deleterious effects of older fathers on general cognitive ability as young adults
      may be counter-balanced by other potentially beneficial factors.

PMID- 24116229
TI  - omega3-PUFAs exert anti-inflammatory activity in visceral adipocytes from
      colorectal cancer patients.
AB  - OBJECTIVE: The aim of this study was to correlate specific fatty acid profiles of
      visceral white adipose tissue (WAT) with inflammatory signatures potentially
      associated with colorectal cancer (CRC). METHODS: Human adipocytes were isolated
      from biopsies of visceral WAT from 24 subjects subdivided in four groups: normal
      weight (BMI 22.0-24.9 Kg/m2) and over-weight/obese (BMI 26.0-40.0 Kg/m2),
      affected or not by CRC. To define whether obesity and/or CRC affect the
      inflammatory status of WAT, the activation of the pro-inflammatory STAT3 and the
      anti-inflammatory PPARgamma transcription factors as well as the expression of
      adiponectin were analyzed by immunoblotting in adipocytes isolated from each
      group of subjects. Furthermore, to evaluate whether differences in inflammatory
      WAT environment correlate with specific fatty acid profiles, gas-chromatographic
      analysis was carried out on WAT collected from all subject categories. Finally,
      the effect of the omega3 docosahexaenoic acid treatment on the balance between
      pro- and anti-inflammatory factors in adipocytes was also evaluated. RESULTS: We
      provide the first evidence for the existence of a pro-inflammatory environment in
      WAT of CRC patients, as assessed by the up-regulation of STAT3, and the
      concomitant decrease of PPARgamma and adiponectin with respect to healthy
      subjects. WAT inflammatory status was independent of obesity degree but
      correlated with a decreased omega3-/omega6-polyunsaturated fatty acid ratio.
      These observations suggested that qualitative changes, other than quantitative
      ones, in WAT fatty acid may influence tissue dysfunctions potentially linked to
      inflammatory conditions. This hypothesis was further supported by the finding
      that adipocyte treatment with docosahexaenoic acid restored the equilibrium
      between STAT3 and PPARgamma. CONCLUSION: Our results suggest that adipocyte
      dysfunctions occur in CRC patients creating a pro-inflammatory environment that
      might influence cancer development. Furthermore, the protective potential of
      docosahexaenoic acid in re-establishing the equilibrium between pro- and anti
      inflammatory factors might represent a useful tool for preventive and therapeutic
      strategies.

PMID- 24116231
TI  - Optimal differentiation of in vitro keratinocytes requires multifactorial
      external control.
AB  - For almost 30 years, keratinocyte differentiation has been studied in numerous
      cell models including keratinocyte primary culture with various supplemented
      culture media. In this respect, it has become quite difficult to draw comparisons
      between studies using such a variety of culture conditions. Serum-free condition
      with low calcium has been used to culture basal proliferating cells, though
      differentiation is induced by various procedures. These latter include the
      addition of calcium at mM concentration and a concomitant addition of serum and
      calcium. Lowering the incubation temperature of cells has also been reported to
      induce a premature differentiation of keratinocytes in organotypic skin culture.
      This effect of temperature on keratinocyte differentiation has been poorly
      depicted, although average human skin temperature has been shown to be about 32 
      degrees C. However, studying differentiation and quantifying shifts in the
      differentiation rate of a cell population implies to precisely know i) the
      proportion of differentiated cells in the whole population, and ii) to which
      extent and to which level of expression, the induction of a gene or a protein
      might be considered as a marker of differentiation. This lack has rarely been
      taken into consideration and has surely led to over-interpretations of single
      protein induction and to consequent extrapolations to real differentiation
      processes. By means of paralleled analyses with immunocytofluorescence, flow
      cytometry, and with multiple differentiation markers quantify by qPCR and western
      blot, we studied the paradoxical connection between calcium, serum, multilayer
      culture and incubation temperature on the differentiation of in vitro
      keratinocytes. Conversely to previous reports, we have shown that calcium switch
      is indeed a potent model for inducing calcium-dependent genes, but is not an
      efficient procedure when one wishes to assess the keratinocyte differentiation
      rate. Moreover, we have demonstrated that a synergic stimulation by calcium,
      serum, confluence and lower incubation temperature amplified the differentiation
      rate.

PMID- 24116232
TI  - Expression of the TEL-Syk fusion protein in hematopoietic stem cells leads to
      rapidly fatal myelofibrosis in mice.
AB  - The TEL-Syk fusion protein was isolated from a patient with myelodysplasia with
      megakaryocyte blasts. Expression of TEL-Syk transforms interleukin-3 (IL-3)
      dependent Ba/F3 cells in vitro by deregulating STAT5-mediated signal transduction
      pathways. In vivo, TEL-Syk expression in pre-B cells blocks B cell
      differentiation, leading to lymphoid leukemia. Here, we demonstrate that TEL-Syk
      introduced into fetal liver hematopoietic cells, which are then adoptively
      transferred into lethally irradiated recipients, leads to an aggressive
      myelodysplasia with myelofibrosis that is lethal in mice by 60-75 days.
      Expression of TEL-Syk induces a short-lived myeloexpansion that is rapidly
      followed by bone marrow failure and extreme splenic/hepatic fibrosis accompanied
      by extensive apoptosis. The disease is dependent on Syk kinase activity. Analysis
      of serum from TEL-Syk mice reveals an inflammatory cytokine signature reminiscent
      of that found in the sera from patients and mouse models of myeloproliferative
      neoplasms. TEL-Syk expressing cells showed constitutive STAT5 phosphorylation,
      which was resistant to JAK inhibition, consistent with deregulated cytokine
      signaling. These data indicate that expression of TEL-Syk in fetal liver
      hematopoietic cells results in JAK-independent STAT5 phosphorylation ultimately
      leading to a uniquely aggressive and lethal form of myelofibrosis. 

PMID- 24116233
TI  - Plant functional diversity and species diversity in the Mongolian steppe.
AB  - BACKGROUND: The Mongolian steppe is one of the most important grasslands in the
      world but suffers from aridization and damage from anthropogenic activities.
      Understanding structure and function of this community is important for the
      ecological conservation, but has seldom been investigated. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, a total of 324 quadrats located on the three main types
      of Mongolian steppes were surveyed. Early-season perennial forbs (37% of total
      importance value), late-season annual forbs (33%) and late-season perennial forbs
      (44%) were dominant in meadow, typical and desert steppes, respectively. Species
      richness, diversity and plant functional type (PFT) richness decreased from the
      meadow, via typical to desert steppes, but evenness increased; PFT diversity in
      the desert and meadow steppes was higher than that in typical steppe. However,
      above-ground net primary productivity (ANPP) was far lower in desert steppe than
      in the other two steppes. In addition, the slope of the relationship between
      species richness and PFT richness increased from the meadow, via typical to
      desert steppes. Similarly, with an increase in species diversity, PFT diversity
      increased more quickly in both the desert and typical steppes than that in meadow
      steppe. Random resampling suggested that this coordination was partly due to a
      sampling effect of diversity. CONCLUSIONS/SIGNIFICANCE: These results indicate
      that desert steppe should be strictly protected because of its limited functional
      redundancy, which its ecological functioning is sensitive to species loss. In
      contrast, despite high potential forage production shared by the meadow and
      typical steppes, management of these two types of steppes should be different:
      meadow steppe should be preserved due to its higher conservation value
      characterized by more species redundancy and higher spatial heterogeneity, while
      typical steppe could be utilized moderately because its dominant grass genus
      Stipa is resistant to herbivory and drought.

PMID- 24116234
TI  - Identification of novel vaccine candidates against multidrug-resistant
      Acinetobacter baumannii.
AB  - Acinetobacter baumannii is an emerging opportunistic bacterium associated with
      nosocomial infections in intensive care units. The alarming increase in
      infections caused by A. baumannii is strongly associated with enhanced resistance
      to antibiotics, in particular carbapenems. This, together with the lack of a
      licensed vaccine, has translated into significant economic, logistic and health
      impacts to health care facilities. In this study, we combined reverse vaccinology
      and proteomics to identify surface-exposed and secreted antigens from A.
      baumannii. Using in silico prediction tools and comparative genome analysis in
      combination with in vitro proteomic approaches, we identified 42 antigens that
      could be used as potential vaccine targets. Considering the paucity of effective
      antibiotics available to treat multidrug-resistant A. baumannii infections, these
      vaccine targets may serve as a framework for the development of a broadly
      protective multi-component vaccine, an outcome that would have a major impact on
      the burden of A. baumannii infections in intensive care units across the globe. 

PMID- 24116237
TI  - Correction: The CD44high Tumorigenic Subsets in Lung Cancer Biospecimens Are
      Enriched for Low miR-34a Expression.
AB  - [This corrects the article on p. e73195 in vol. 8.].

PMID- 24116236
TI  - Age-dependent face detection and face categorization performance.
AB  - Empirical studies on the development of face processing skills with age show
      inconsistent patterns concerning qualitative vs. quantitative changes over time
      or the age range for peak cognitive performance. In the present study, we tested
      the proficiency in face detection and face categorization with a large sample of
      participants (N = 312; age range: 2-88 yrs). As test objects, we used so-called
      Mooney faces, two-tone (black and white) images of faces lacking critical
      information of a local, featural and relational nature, reflecting difficult real
      world face processing conditions. We found that performance in the assessment of
      gender and age from Mooney faces increases up to about age 15, and decreases from
      65 years on. The implications of these findings are discussed in the light of
      classic and recent findings from face development literature. 

PMID- 24116235
TI  - Posttraumatic stress disorder increases sensitivity to long term losses among
      patients with major depressive disorder.
AB  - BACKGROUND: Decisions under risk and with outcomes that are delayed in time are
      ubiquitous in real life and can have a significant impact on the health and
      wealth of the decision-maker. Despite its potential relevance for real-world
      choices, the degree of aberrant risky and intertemporal decision-making in
      patients suffering from major depressive disorder (MDD) and posttraumatic stress
      disorder (PTSD) has received little attention to date. METHOD: We used a case
      control design to compare decision-making in healthy control subjects (N=16)
      versus untreated depressed subjects in a current major depressive episode (N=20).
      In order to examine how major depressive disorder (MDD) may impact decision
      making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes
      in the domain of gains and losses using choice paradigms from neuroeconomics. In
      a pre-planned analysis, depressed subjects were subdivided into those with
      primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD
      without PTSD (MDD-only). Choice behavior was modeled via a standard econometric
      model of intertemporal choice, a quasi-hyperbolic temporal discounting function,
      which was estimated for each subject group separately. RESULTS: Under conditions
      of potential gain, depressed subjects demonstrated greater discounting for gains
      across all time frames compared to controls. In the realm of losses, both
      subgroups of depressed subjects discounted more steeply than controls for short
      time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD
      subjects showed shallower discounting rates relative to MDD-only subjects, who
      continued to discount future losses steeply. Risk attitudes did not contribute to
      differences in intertemporal choice. CONCLUSIONS: Depressed patients make choices
      that minimize current pain and maximize current reward, despite severe later
      consequences or lost opportunities. Anxiety associated with PTSD may serve as a
      partially protective factor in decision-making about long-term potential losses
      compared to MDD patients without PTSD.

PMID- 24116238
TI  - Correction: Quantification of Collagen Ultrastructure after Penetrating
      Keratoplasty - Implications for Corneal Biomechanics.
AB  - [This corrects the article on p. e68166 in vol. 8.].

PMID- 24116239
TI  - Correction: Two Variants of the C-Reactive Protein Gene Are Associated with Risk
      of Pre-Eclampsia in an American Indian Population.
AB  - [This corrects the article on p. e71231 in vol. 8.].

PMID- 24116240
TI  - Correction: Competence-Independent Activity of Pneumococcal Enda Mediates
      Degradation of Extracellular DNA and Nets and Is Important for Virulence.
AB  - [This corrects the article on p. e70363 in vol. 8.].

PMID- 24116241
TI  - Correction: The Detection and Sequencing of a Broad-Host-Range Conjugative IncP
      1beta Plasmid in an Epidemic Strain of Mycobacterium abscessus subsp. bolletii.
AB  - [This corrects the article on p. e60746 in vol. 8.].

PMID- 24116242
TI  - Correction: Chimeric Rhinoviruses Displaying MPER Epitopes Elicit Anti-HIV
      Neutralizing Responses.
AB  - [This corrects the article on p. e72205 in vol. 8.].

PMID- 24116244
TI  - Correction: Aureochrome 1a Is Involved in the Photoacclimation of the Diatom
      Phaeodactylum tricornutum.
AB  - [This corrects the article on p. e74451 in vol. 8.].

PMID- 24116243
TI  - Correction: Persistence of Borrelia burgdorferi in Rhesus Macaques following
      Antibiotic Treatment of Disseminated Infection.
AB  - [This corrects the article on p. e29914 in vol. 7.].

PMID- 24116245
TI  - Correction: Type-Specific Cell Line Models for Type-Specific Ovarian Cancer
      Research.
AB  - [This corrects the article on p. e72162 in vol. 8.].

PMID- 24116246
TI  - Correction: Prediction of microRNAs Associated with Human Diseases Based on
      Weighted k Most Similar Neighbors.
AB  - [This corrects the article on p. e70204 in vol. 8.].

PMID- 24116247
TI  - Correction: New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus
      Genotype 1b RNA Replication.
AB  - [This corrects the article on p. e72519 in vol. 8.].

PMID- 24116248
TI  - Correction: Economic Burden of Human Papillomavirus-Related Diseases in Italy.
AB  - [This corrects the article on p. e49699 in vol. 7.].

PMID- 24116249
TI  - Correction: Composition and Expression of Genes Encoding Carbohydrate-Active
      Enzymes in the Straw-Degrading Mushroom Volvariella volvacea.
AB  - [This corrects the article on p. e58780 in vol. 8.].

PMID- 24116250
TI  - Correction: Investigating and Learning Lessons from Early Experiences of
      Implementing ePrescribing Systems into NHS Hospitals: A Questionnaire Study.
AB  - [This corrects the article on p. e53369 in vol. 8.].

PMID- 24116251
TI  - Correction: Bilateral Descending Hypothalamic Projections to the Spinal
      Trigeminal Nucleus Caudalis in Rats.
AB  - [This corrects the article on p. e73022 in vol. 8.].

PMID- 24116252
TI  - Correction: Modeling Social Network Topologies in Elementary Schools.
AB  - [This corrects the article on p. e55371 in vol. 8.].

PMID- 24116253
TI  - Correction: Changes in Mouse Thymus and Spleen after Return from the STS-135
      Mission in Space.
AB  - [This corrects the article on p. e75097 in vol. 8.].

PMID- 24116254
TI  - Correction: Harming Ourselves and Defiling Others: What Determines a Moral
      Domain?
AB  - [This corrects the article on p. e74434 in vol. 8.].

PMID- 24116255
TI  - Correction: Magmas Overexpression Inhibits Staurosporine Induced Apoptosis in Rat
      Pituitary Adenoma Cell Lines.
AB  - [This corrects the article on p. e75194 in vol. 8.].

PMID- 24116256
TI  - Correction: Actin Cytoskeleton Regulates Hippo Signaling.
AB  - [This corrects the article on p. e73763 in vol. 8.].

PMID- 24116258
TI  - Correction: Anterior Segment Optical Coherence Tomography for the Quantitative
      Evaluation of the Anterior Segment Following Boston Keratoprosthesis.
AB  - [This corrects the article on p. e70673 in vol. 8.].

PMID- 24116259
TI  - Correction: Directed In Vitro Myogenesis of Human Embryonic Stem Cells and Their
      In Vivo Engraftment.
AB  - [This corrects the article on p. e72023 in vol. 8.].

PMID- 24116260
TI  - Correction: Evidence for the Circulation of Equine Encephalosis Virus in Israel
      since 2001.
AB  - [This corrects the article on p. e70532 in vol. 8.].

PMID- 24116261
TI  - Cortical blindness after complicated general anesthesia in urological surgery.
AB  - PATIENT: Male, 4 FINAL DIAGNOSIS: Cortical blindness after complicated general
      anesthesia Symptoms: Blindness * fine motor activity derangements MEDICATION: -
      Clinical Procedure: General anesthesia for unilateral inguinal hydrocelectomy
      Specialty: Anesthesiology. OBJECTIVE: Rare disease. BACKGROUND: We report a case
      of transient cortical blindness after urological surgery. CASE REPORT: We present
      the case of a 4-year-old boy with visual loss following complicated general
      anesthesia during urological surgery. The results of ophthalmological
      examinations were normal. The complication was diagnosed as cortical blindness
      after obtaining an extinguished flash visual-evoked potential (flash VEP). The
      visual acuity persisted to be hand motion after 4 months. CONCLUSIONS: We report
      a very rare case of cortical blindness after urological surgery. Unrecognized
      causes of cortical blindness are common in the children. Because of the long
      survival and increasing surgical management in this age group, it is of great
      importance and perhaps it will be necessary to alert parents about it.
      Anesthesiologists have a unique opportunity to facilitate positive outcomes for
      these patients through risk identification and appropriate management.

PMID- 24116262
TI  - A teenager with tetralogy of fallot becomes a soccer player.
AB  - PATIENT: Male, 0 FINAL DIAGNOSIS: Tetralogy of Fallot Symptoms: - MEDICATION: -
      Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Unusual or unexpected
      effect of treatment. BACKGROUND: Tetralogy of Fallot (ToF) is the most common
      form of cyanotic congenital defect. Adult subjects with results of repair of
      tetralogy of Fallot may present post-surgical consequences that limit their
      physical capacity and thus their ability to compete in sports. Conversely, adults
      with excellent repair of congenital heart disease may have a chance to
      participate in competitive sports. CASE REPORT: This case report illustrates the
      clinical course of a teenager with an outcome of surgical repair for TOF and
      demonstrates the boy's excellent physical capacity that ensures his ability to
      play soccer. CONCLUSIONS: This case report raises the question of the possible
      revision of the criteria of the Italian COCIS protocol in terms of corrected
      congenital heart disease.

PMID- 24116263
TI  - Sensomotor axonal peripheral neuropathy as a first complication of polycythemia
      rubra vera: A report of 3 cases.
AB  - PATIENT: Female, 64 FINAL DIAGNOSIS: Polycythemia rubra vera Symptoms: Burning
      pain * cramps * hypesthesia * itching * paresthesia MEDICATION: - Clinical
      Procedure: - Specialty: Neurology. OBJECTIVE: Unusual clinical course.
      BACKGROUND: The association between polycythemia vera and peripheral neuropathy
      has been described previously but only as a late complication and only with
      sensory axonal polyneuropathy. We presume the cause of polyneuropathy was hypoxia
      due to higher blood viscosity and dysfunction of platelet aggregation. CASES
      REPORT: We report the cases of 3 female patients with symptoms and signs of
      slowly progressive sensorimotor axonal polyneuropathy confirmed with clinical and
      neurographic examination as first complication of polycythemia vera, which
      progressed to a major complication. Axonal damage was irreversible despite
      venipuncture. CONCLUSIONS: Polycythemia vera is rarely manifested with symptoms
      of sensomotor polyneuropathy as the first signs of the disease, and should
      therefore be recognized by physicians to prevent further axonal damage and major
      complications of disease by venipuncture or cytostatic therapy.

PMID- 24116264
TI  - Diagnosis of a huge right atrial thrombus during coronary artery bypass graft
      surgery.
AB  - PATIENT: Male, 73 FINAL DIAGNOSIS: Coronary artery thrombosis Symptoms: Angina
      pectoris * short of breath MEDICATION: - Clinical Procedure: CABG Specialty:
      Cardiology. OBJECTIVE: Management of emergency care. BACKGROUND: Intra-operative
      formation of a thrombus in the right heart is rare and might be unrecognized.
      However, it can be associated with severe consequences, including pulmonary
      embolism and death. CASE REPORT: We report the case of a 73-year-old man who
      presented to the cardiologist with angina pectoris and rare shortness of breath.
      Coronary artery bypass grafting (CABG) was performed due to multi-vessel disease.
      Because of hemodynamic insufficiency, an intra-operative transesophageal
      echocardiogram (TEE) was performed and a huge free-floating thrombus was
      detected. Multiple thrombi were removed from the right heart and pulmonary
      arteries. The patient died after cardiopulmonary bypass support and 12 hours of
      intensive care. CONCLUSIONS: In this case report, we emphasize the importance of
      the TEE during the preoperational period and during CABG, as well as in the
      preoperative evaluation of pulmonary hypertension.

PMID- 24116265
TI  - Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer:
      Case report and discussion.
AB  - PATIENT: Female, 59 FINAL DIAGNOSIS: Paraneoplastic limbic encephalitis Symptoms:
      Seizure * memory changes * decreased concentration MEDICATION: Chemotherapy
      Clinical Procedure: Cerebral images Specialty: Hematology * Oncology. OBJECTIVE:
      Challenging differential diagnosis. BACKGROUND: Paraneoplastic neurological
      disorders (PND) are defined as remote effects on the nervous system that are not
      caused directly by the tumor, its metastases, or metabolic disruptions. This
      syndrome occurs in less than 1 per 10,000 patients diagnosed with a malignancy.
      Many antibodies are found in the central nervous system in PND, the most well
      known are Anti-Hu, Tr, CV2 Ta, Yo, Ri and amphiphysin. Paraneoplastic limbic
      encephalitis occurs due to involvement of the limbic system secondary to an
      autoimmune response to neurons of the brain provoked by the antibodies. PATIENTs,
      thus, present with seizures, changes in mood, memory, and personality. CASE
      REPORT: Fifty-nine years-old female patient presented with seizures, decreased
      concentration and memory changes. Laboratory workup was remarkable for
      hyponatremia. Further workup included brain computerized tomography (CT) and
      magnetic resonance imaging (MRI), which suggested a diagnosis of encephalitis for
      limbic encephalitis. Anti-Hu, anti-Ma and NMDA-receptor antibodies were requested
      of which Anti Hu antibodies were positive. Transbronchial biopsy was obtained
      which confirmed the diagnosis of small cell lung cancer. CONCLUSIONS: A very high
      index of suspicion should thus be present when patients present with
      paraneoplastic abnormalities. It must be emphasized that limbic encephalitis (LE)
      occurs at an early stage of the disease development and therefore the detection
      of paraneoplastic LE can lead to a quicker identification of the underlying
      malignancy and a better outcome.

PMID- 24116266
TI  - Gut feelings: bacteria and the brain.

PMID- 24116267
TI  - Do cytokines really sing the blues?

PMID- 24116268
TI  - Single-Molecule Analysis of Cytochrome c Folding by Monitoring the Lifetime of an
      Attached Fluorescent Probe.
AB  - Conformational dynamics of proteins are important for function. However,
      obtaining information about specific conformations is difficult for samples
      displaying heterogeneity. Here, time-resolved fluorescence resonance energy
      transfer is used to characterize the folding of single cytochrome c molecules. In
      particular, measurements of the fluorescence lifetimes of individual cytochrome c
      molecules labeled with a single dye that is quenched by energy transfer to the
      heme were used to monitor conformational transitions of the protein under
      partially denaturing conditions. These studies indicate significantly more
      conformational heterogeneity than has been described previously. Importantly, the
      use of a purified singly-labeled sample made a direct comparison to ensemble data
      possible. The distribution of lifetimes of single-proteins was compared to the
      distribution of lifetimes determined from analysis of ensemble lifetime
      fluorescence data. The results show broad agreement between single-molecule and
      ensemble data, with a similar range of lifetimes. However, the single-molecule
      data reveal greater conformational heterogeneity.

PMID- 24116270
TI  - Cyclic peptides as therapeutic agents and biochemical tools.
AB  - There are many cyclic peptides with diverse biological activities, such as
      antibacterial activity, immunosuppressive activity, and anti-tumor activity, and
      so on. Encouraged by natural cyclic peptides with biological activity, efforts
      have been made to develop cyclic peptides with both genetic and synthetic
      methods. The genetic methods include phage display, intein-based cyclic peptides,
      and mRNA display. The synthetic methods involve individual synthesis, parallel
      synthesis, as well as split-and-pool synthesis. Recent development of cyclic
      peptide library based on split-and-pool synthesis allows on-bead screening, in
      solution screening, and microarray screening of cyclic peptides for biological
      activity. Cyclic peptides will be useful as receptor agonist/antagonist, RNA
      binding molecule, enzyme inhibitor and so on, and more cyclic peptides will
      emerge as therapeutic agents and biochemical tools. 

PMID- 24116271
TI  - Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A
      Receptor Stimulation: A Possible Role in Neuroprotection.
AB  - Oroxylin A is a flavone isolated from a medicinal herb reported to be effective
      in reducing the inflammatory and oxidative stresses. It also modulates the
      production of brain derived neurotrophic factor (BDNF) in cortical neurons by the
      transactivation of cAMP response element-binding protein (CREB). As a
      neurotrophin, BDNF plays roles in neuronal development, differentiation,
      synaptogenesis, and neural protection from the harmful stimuli. Adenosine A2A
      receptor colocalized with BDNF in brain and the functional interaction between
      A2A receptor stimulation and BDNF action has been suggested. In this study, we
      investigated the possibility that oroxylin A modulates BDNF production in
      cortical neuron through the regulation of A2A receptor system. As ex-pected,
      CGS21680 (A2A receptor agonist) induced BDNF expression and release, however, an
      antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production.
      Oroxylin A activated the PI3K-Akt-GSK-3beta signaling pathway, which is inhibited
      by ZM241385 and the blockade of the signaling pathway abolished the increase in
      BDNF production. The physiological roles of oroxylin A-induced BDNF production
      were demonstrated by the increased neurite extension as well as synapse formation
      from neurons. Overall, oroxylin A might regulate BDNF production in cortical
      neuron through A2A receptor stimulation, which promotes cellular survival,
      synapse formation and neurite extension. 

PMID- 24116272
TI  - The role of intestinal microflora in anti-inflammatory effect of baicalin in
      mice.
AB  - Baicalin, a main constituent of the rhizome of Scutellaria baicalensis, is
      metabolized to baicalein and oroxylin A in the intestine before its absorption.
      To understand the role of intestinal microflora in the pharmacological activities
      of baicalin, we investigated its anti-inflammatory effect in mice treated with
      and without antibiotics. Orally administered baicalin showed the anti
      inflammatory effect in mice than intraperitoneally treated one, apart from
      intraperitoneally administered its metabolites, baicalein and oroxylin A, which
      potently inhibited LPS-induced inflammation. Of these metabolites, oroxylin A
      showed more potent anti-inflammatory effect. However, treatment with the mixture
      of cefadroxil, oxytetracycline and erythromycin (COE) significantly attenuated
      the anti-inflammatory effect of orally administered baicalin in mice. Treatment
      with COE also reduced intestinal bacterial fecal beta-glucuronidase activity. The
      metabolic activity of human stools is significantly different between
      individuals, but neither between ages nor between male and female. Baicalin was
      metabolized to baicalein and oroxylin A, with metabolic activities of 1.427 +/-
      0.818 and 1.025 +/- 0.603 pmol/min/mg wet weight, respectively. Baicalin and its
      metabolites also inhibited the expression of pro-inflammatory cytokines, TNF
      alpha and IL-1beta, and the activation of NF-kappaB in LPS-stimulated peritoneal
      macrophages. Of them, oroxylin A showed the most potent inhibition. Based on
      these findings, baicalin may be metabolized to baicalein and oroxylin A by
      intestinal microflora, which enhance its anti-inflammatory effect by inhibiting
      NF-kappaB activation. 

PMID- 24116269
TI  - Glutamate receptor abnormalities in schizophrenia: implications for innovative
      treatments.
AB  - Schizophrenia is a devastating psychiatric illness that afflicts 1% of the
      population worldwide, resulting in substantial impact to patients, their
      families, and health care delivery systems. For many years, schizophrenia has
      been felt to be associated with dysregulated dopaminergic neurotransmission as a
      key feature of the pathophysiology of the illness. Although numerous studies
      point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot
      completely account for all of the symptoms seen in schizophrenia, and dopamine
      based treatments are often inadequate and can be associated with serious side
      effects. More recently, converging lines of evidence have suggested that there
      are abnormalities of glutamate transmission in schizophrenia. Glutamatergic
      neurotransmission involves numerous molecules that facilitate glutamate release,
      receptor activation, glutamate reuptake, and other synaptic activities. Evidence
      for glutamatergic abnormalities in schizophrenia primarily has implicated the
      NMDA and AMPA subtypes of the glutamate receptor. The expression of these
      receptors and other molecules associated with glutamate neurotransmission has
      been systematically studied in the brain in schizophrenia. These studies have
      generally revealed region- and molecule-specific changes in glutamate receptor
      transcript and protein expression in this illness. Given that glutamatergic
      neurotransmission has been implicated in the pathophysiology of schizophrenia,
      recent drug development efforts have targeted the glutamate system. Much effort
      to date has focused on modulation of the NMDA receptor, although more recently
      other glutamate receptors and transporters have been the targets of drug
      development. These efforts have been promising thus far, and ongoing efforts to
      develop additional drugs that modulate glutamatergic neurotransmission are
      underway that may hold the potential for novel classes of more effective
      treatments for this serious psychiatric illness. 

PMID- 24116273
TI  - Destabilization of TNF-alpha mRNA by Rapamycin.
AB  - Stimulation of mast cells through the high affinity IgE receptor (FcepsilonRI)
      induces degranulation, lipid mediator release, and cytokine secretion leading to
      allergic reactions. Although various signaling pathways have been characterized
      to be involved in the FcepsilonRI-mediated responses, little is known about the
      precious mechanism for the expression of tumor necrosis factor-alpha (TNF-alpha)
      in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian
      target of rapamycin (mTOR), reduces the expression of TNF-alpha in rat basophilic
      leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells
      increases the expression of TNF-alpha and activates various signaling molecules
      including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigen-induced
      TNF-alpha mRNA level, while other kinase inhibitors have no effect on TNF-alpha
      mRNA level. These data indicate that mTOR signaling pathway is the main
      regulation mechanism for antigen-induced TNF-alpha expression. TNF-alpha mRNA
      stability analysis using reporter construct containing TNF-alpha
      adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF
      alpha mRNA via regulating the AU-rich element of TNF-alpha mRNA. The antigen
      induced activation of S6K1 is inhibited by specific kinase inhibitors including
      mTOR, PI3K, PKC and Ca(2+)chelator inhibitor, while TNF-alpha mRNA level is
      reduced only by rapamycin treatment. These data suggest that the effects of
      rapamycin on the expression of TNF-alpha mRNA are not mediated by S6K1 but
      regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway
      is a novel regulation mechanism for antigen-induced TNF-alpha expression in RBL
      2H3 cells. 

PMID- 24116274
TI  - WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the
      Production of Pro-Inflammatory Mediators in Cells via Inhibition of IkappaB
      Signaling Pathways.
AB  - WIN-34B showed analgesic and anti-inflammatory effects in various animal models
      of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B
      inhibits pain and inflammation in vivo remains to be elucidated. We investigated
      the molecular mechanisms of the actions of WIN-34B using various in vitro models
      using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA
      FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of
      IL-6, PGE2, and MMP-13 in IL-1beta-stimulated RA FLSs in a dose-dependent manner.
      The mRNA levels were also inhibited by WIN-34B. The level of PGE2, NO, IL-1beta,
      and TNF-alpha were inhibited by WIN-34B at different concentrations in LPS
      stimulated RAW264.7 cells. The production of NO and PGE2 was inhibited by WIN-34B
      in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these
      effects were comparable to the positive control, celecoxib or indomethacin.
      IkappaB signaling pathways were inhibited by WIN-34B, and the migration of NF
      kappaB into the nucleus was inhibited, which is consistent with the degradation
      of IkappaB-alpha. Taken together, the results suggest that WIN-34B has potential
      as a therapeutic drug to reduce pain and inflammation by inhibiting the
      production of pro-inflammatory mediators. 

PMID- 24116275
TI  - Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix
      Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human
      Keratinocytes.
AB  - The matrix metalloproteinase (MMP) family is involved in the breakdown of the
      extracellular matrix during normal physiological processes such as embryonic
      development, reproduction, and tissue remodeling, as well as in disease processes
      such as pathological aging, arthritis, and metastasis. Oxidative conditions
      generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [H2O2]) in cells,
      which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1).
      MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In
      this study, baicalein (5,6,7-trihydroxyflavone) was investigated for its in vitro
      activity against H2O2-induced damage using a human skin keratinocyte model.
      Baicalein pretreatment significantly inhibited H2O2-induced up-regulation of MMP
      1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT
      keratinocytes. In addition, baicalein decreased the transcriptional activity of
      activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components
      of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced
      phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N
      terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The
      results of this study suggest that baicalein is involved in the inhibition of
      oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1
      signaling pathway. 

PMID- 24116276
TI  - Apigenin Sensitizes Huh-7 Human Hepatocellular Carcinoma Cells to TRAIL-induced
      Apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management
      of cancer because of its selective cytotoxicity to cancer cells. However, some
      cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies
      are required to overcome TRAIL resistance. Here, we examined the synergistic
      apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found
      that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell
      growth compared to either agent alone by inducing apoptosis. Combined treatment
      with apigenin and TRAIL induced chromatin condensation and the cleavage of poly
      (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin
      combination was quantified by annexin V/PI flow cytometry analysis. Western blot
      analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by
      activating both intrinsic and extrinsic apoptotic pathway-related caspases. The
      augmented apoptotic effect by TRAIL/apigenin combination was accompanied by
      triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2
      ratio up-regulation. Our results demonstrate that combination of TRAIL and
      apigenin facilitates apoptosis in Huh-7 cells. 

PMID- 24116277
TI  - Anthocyanin Extracts from Black Soybean (Glycine max L.) Protect Human Glial
      Cells Against Oxygen-Glucose Deprivation by Promoting Autophagy.
AB  - Anthocyanins have received growing attention as dietary antioxidants for the
      prevention of oxidative damage. Astrocytes, which are specialized glial cells,
      exert numerous essential, complex functions in both healthy and diseased central
      nervous system (CNS) through a process known as reactive astrogilosis. Therefore,
      the maintenance of glial cell viability may be important because of its role as a
      key modulator of neuropathological events. The aim of this study was to
      investigate the effect of anthocyanin on the survival of glial cells exposed to
      oxidative stress. Our results demonstrated that anthocyanin extracts from black
      soybean increased survival of U87 glioma cells in a dose dependent manner upon
      oxygen-glucose deprivation (OGD), accompanied by decrease levels of reactive
      oxygen species (ROS). While treatment cells with anthocyanin extracts or OGD
      stress individually activated autophagy induction, the effect was significantly
      augmented by pretreatment cells with anthocyanin extracts prior to OGD. The
      contribution of autophagy induction to the protective effects of anthocyanin was
      verified by the observation that silencing the Atg5 expression, an essential
      regulator of autophagy induction, reversed the cytoprotective effect of
      anthocyanin extracts against OGD stress. Treatment of U87 cells with rapamycin,
      an autophagy inducer, increased cell survival upon OGD stress comparable to
      anthocyanin, indicating that autophagy functions as a survival mechanism against
      oxidative stress-induced cytotoxicity in glial cells. Our results, therefore,
      provide a rationale for the use of anthocyanin as a preventive agent for brain
      dysfunction caused by oxidative damage, such as a stroke. 

PMID- 24116278
TI  - Effects of ginsenosides rg1 on osteoblasts cultured with ti particles.
AB  - The aim of this study was to explore the role and effect of ginsenosides Rg1 on
      osteoblasts cultured with Ti particles. Osteoblasts from neonatal rats were
      cultured with particles and different doses of Rg1, the main active ingredient in
      ginsenosides Rg1. We found that the COX-2, PGE2, TNF-alpha, IL-1, and IL -6
      concentrations in the medium of cells cultured with Ti particles significantly
      increased as compared with that of the control cells (p<0.05 or p<0.01). In
      addition, cells cultured with Ti particles alone exhibited the highest
      concentrations of these molecules. The PGE2, TNF-alpha, IL-1, and IL-6 levels in
      the medium of cells cultured with Rg1 were in between those of the control cells
      and the cells cultured with Ti particles alone. The IL-1ra level in the group
      cultured with Ti and medium-dose Rg1 was the highest followed by the cells
      cultured with Ti and high-dose Rg1 and those cultured with Ti and low-dose Rg1
      (p<0.05). In conclusion, ginsenosides can reduce the levels of inflammatory
      cytokines produced by osteoblasts on induction with Ti particles and can prevent
      prosthesis loosening. 

PMID- 24116279
TI  - Anti-Cancer Effect of IN-2001 in T47D Human Breast Cancer.
AB  - Histone deacetylases (HDACs) are enzymes involved in the remodelling of
      chromatin, and have a key role in the epigenetic regulation of gene expression.
      Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of
      potential anti-cancer agents. In recent years, a number of structurally diverse
      HDAC inhibitors have been identified and these HDAC inhibitors induce growth
      arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo.
      However, the underlying molecular mechanisms remain unclear. This study aimed at
      investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using
      T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC
      inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor
      positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in
      dose-and time-dependent manner. In T47D human breast cancer cells showed anti
      tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were
      related to the cell cycle arrest and induction of apoptosis. Flow cytometry
      studies revealed that IN-2001 showed accumulation of cells at G2/M phase. At the
      same time, IN-2001 treatment time-dependently increased sub-G1 population,
      representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated
      with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as
      other HDAC inhibitors treatment significantly increased p21(WAF1) and p27(KIP1)
      expression. In addition, thymidylate synthase, an essential enzyme for DNA
      replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors
      in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency
      than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and
      eventual apoptosis in human breast cancer possibly through modulation of cell
      cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and
      thymidylate synthase. 

PMID- 24116280
TI  - Effects of Ethyl Acetate Extract of Poncirus trifoliata Fruit for Glucocorticoid
      Induced Osteoporosis.
AB  - Poncirus trifoliata fruit (PTF) affects the digestive and cardiovascular systems,
      and kidney function. The authors studied the effects of ethyl acetate (EtOAc)
      extract of PTF on the activities of osteoblasts and in an animal model. The main
      compounds of the EtOAc extract, naringin and poncirin have been confi rmed by
      HPLC and NMR analysis. Effects of osteoblastic differentiation were mea-sured by
      alkaline phosphatase (ALP) activity, osteopontin (OPN) protein expression and
      osteoprotegerin (OPG) mRNA expression in MC3T3-E1 cells. Also, osteoclast
      differentiation was measured by multinucleated cells (MNCs) formation through
      tartrate resistance acid phosphatase (TRAP)-positive staining. Bone mineral
      density (BMD) was measured before and after treatment with EtOAc extract of PTF
      in prednisolone-induced osteoporotic mice. Dexamethasone (DEX) decreased OPN and
      OPG expression level in MC3T3-E1 cells and ALP activity was decreased by DEX dose
      dependently. EtOAc extract of PTF recovered the levels of ALP activity, and the
      expression of OPN and OPG in MC3T3-E1 cells treated with DEX. In osteoclast
      differentiation, multinucleated TRAP-positive cell formation was significantly
      suppressed by the EtOAc extract of PTF. Total body BMD was restored by EtOAc
      extract of PTF in prednisolone-induced osteoporotic mice. In conclusion, EtOAc
      extract of PTF recovered DEX-mediated deteriorations in osteoblastic and
      osteoclastic functions, and increased BMD in glucocorticoid-induced osteoporosis.

PMID- 24116281
TI  - The Methanol Extract of Azadirachta indica A. Juss Leaf Protects Mice Against
      Lethal Endotoxemia and Sepsis.
AB  - In the present study, the inhibitory effect of neem leaf extract (NLE) on
      lipopolysaccaride (LPS)-induced nitric oxide (NO) and tumor necrosis factor-alpha
      (TNF-alpha) production was examined both in vitro and in vivo. In vitro study
      revealed that NLE treatment (100 MUg/ml) inhibits LPS (100 ng/ml)-induced NO
      production by 96% and TNF-alpha production by 32%. The reduction in NO production
      is probably conferred by the complete suppression of inducible nitric oxide
      synthase (iNOS) expression. Interestingly, in vivo NLE significantly improved the
      survival rate of mice in an experimental sepsis model. Administration of NLE (100
      mg/kg) 24 h before LPS treatment (20 mg/kg) improved the survival rate of mice by
      60%. The inhibition of plasma NO and TNF-alpha production by NLE is likely to
      account for the improved survival of mice. Our results suggest that NLE may
      present a promising avenue in the development of therapeutic agents for the
      treatment of inflammatory diseases. 

PMID- 24116282
TI  - Anti-Arthritic and Analgesic Effect of NDI10218, a Standardized Extract of
      Terminalia chebula, on Arthritis and Pain Model.
AB  - The fruit of Terminalia chebula Retzius has been used as a panacea in India and
      Southeast Asia but its biological activities have not been fully elucidated. Here
      we report anti-arthritic and analgesic effect of NDI10218, a standardized ethanol
      extract of Terminalia chebula, on collagen-induced arthritis and acetic acid
      induced writhing model, respectively. Arthritis was induced in DBA/1J mice by
      immunizing bovine type II collagen and mice were treated with NDI10218 daily for
      5 weeks after the onset of the disease. NDI10218 reduced the arthritis index and
      blocked the synovial hyperplasia in a dose-dependent manner. The serum levels of
      pro-inflammatory cytokines TNF-alpha, IL-6, and IL-1beta were significantly
      reduced in mice treated with NDI10218. Production of the inflammatory IL-17, but
      not immunosuppressive IL-10, was also inhibited in splenocytes isolated from
      NDI10218-treated arthritis mice. Administration of NDI10218 markedly decreased
      the number of T cell subpopulations in the regional lymph nodes of the arthritis
      mice. Finally, NDI10218 reduced the number of abdominal contractions in acetic
      acid-induced writhing model, suggesting an analgesic effect of this extract.
      Taken together, these results suggest that NDI10218 can be a new therapeutic
      candidate for the treatment of rheuma-toid arthritis. 

PMID- 24116283
TI  - 5-Lipoxygenase Inhibition of the Fructus of Foeniculum vulgare and Its
      Constituents.
AB  - The fruits of Foeniculum vulgare (Foeniculi Fructus) have been widely used in
      Chinese medicine as an antiemetic, ameliorating stomach ailments and as an
      analgesic. In order to establish its potential for antiallergic use, inhibitory
      actions of the fruiton 5-lipoxgenase (5-LOX) and beta-hexosaminidase release were
      evaluated. The 70% ethanol extract of this plant material (FR) considerably
      inhibited 5-LOX-catalyzed leukotriene production from A23187-induced rat
      basophilic leukemia (RBL)-1 cells. The IC50 was 3.2 MUg/ml. From this extract, 12
      major compounds including sabinene, fenchone, gamma-terpinene, alpha-pinene,
      limonene, p-anisylacetone, p-anisylaldehyde, estragole (4-allylanisole), trans
      anethole, scopoletin, bergapten and umbelliferone were isolated. And it was found
      that several terpene derivatives including gamma-terpinene and fenchone as well
      as phenylpropanoid, trans-anethole, showed considerable inhibitory action of 5
      LOX. In particular, the IC50 of trans-anethole was 51.6 MU M. In contrast, FR and
      the isolated compounds did not show considerable inhibitory activity on the
      degranulation reaction of beta-hexosaminidase release from antigen-treated RBL
      2H3 cells. Against arachidonic acid-induced ear edema in mice, FR and trans
      anethole showed significant inhibition by oral administration at doses of 100-400
      mg/kg. In conclusion, FR and several major constituents are 5-LOX inhibitors and
      they may have potential for treating 5-LOX-related disorders. 

PMID- 24116284
TI  - Hair-Loss Preventing Effect of Grateloupia elliptica.
AB  - This study was conducted to evaluate the effect of Grateloupia elliptica, a
      seaweed native to Jeju Island, Korea, on the prevention of hair loss. When
      immortalized rat vibrissa dermal papilla cells were treated with extract of G.
      elliptica, the proliferation of dermal papilla cells significantly increased. In
      addition, the G. elliptica extract significantly inhibited the activity of 5alpha
      reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause
      of androgenetic alopecia. On the other hand, the G. elliptica extract promoted
      PGE2 production in HaCaT cells in a dose-dependent manner. The G. elliptica
      extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL
      6, and TNF-alpha production in lipopolysaccharide (LPS)-stimulated bone marrow
      derived dendritic cells. The G. elliptica extract also showed inhibitory activity
      against Pityrosporum ovale, a main cause of dandruff. These results suggest that
      G. elliptica extract has the potential to treat alopecia via the proliferation of
      dermal papilla, 5alpha-reductase inhibition, increase of PGE2 production,
      decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity
      against Pityrosporum ovale. 

PMID- 24116285
TI  - A simple behavioral paradigm to measure impulsive behavior in an animal model of
      attention deficit hyperactivity disorder (ADHD) of the spontaneously hypertensive
      rats.
AB  - Impulsiveness is an important component of many psychiatric disorders including
      Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological
      basis of ADHD is unresolved, behavioral tests in animal models have become
      indispensable tools for improving our understanding of this disorder. In the
      punishment/extinction paradigm, impulsivity is shown by subjects that persevere
      with responding despite punishment or unrewarded responses. Exploiting this
      principle, we developed a new behavioral test that would evaluate impulsivity in
      the most validated animal model of ADHD of the Spontaneously Hypertensive rat
      (SHR) as compared with the normotensive "control" strain, the Wistar Kyoto rat
      (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking
      test (EFSDT), water-deprived rats should pass over an electrified quadrant of the
      EFSDT apparatus to drink water. We reasoned that impulsive animals show increased
      frequency to drink water even with the presentation of an aversive consequence
      (electro-shock). Through this assay, we showed that the SHR was more impulsive
      than the WKY as it demonstrated more "drinking attempts" and drinking frequency.
      Methylphenidate, the most widely used ADHD medication, significantly reduced
      drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may
      be considered as another behavioral tool to measure impulsivity in animal disease
      models, especially in the context of ADHD. 

PMID- 24116287
TI  - Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes.
AB  - The molecular mechanisms by which a variety of naturally-occurring dietary
      compounds exert chemopreventive effects have been a subject of intense scientific
      investigations. Induction of phase II detoxification and anti-oxidant enzymes
      through activation of Nrf2/ARE-dependent gene is recognized as one of the major
      cellular defense mechanisms against oxidative or xenobiotic stresses and
      currently represents a critical chemopreventive mechanism of action. In the
      present review, the functional significance of Keap1/Nrf2 protein module in
      regulating ARE-dependent phase II detoxification and anti-oxidant gene expression
      is discussed. The biochemical mechanisms underlying the phosphorylation and
      expression of Keap1/Nrf2 proteins that are controlled by the intracellular
      signaling kinases and ubiquitin-mediated E3 ligase system as well as control of
      nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES)
      are described. 

PMID- 24116286
TI  - Matrix metalloproteinases, new insights into the understanding of
      neurodegenerative disorders.
AB  - Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that
      are responsible for degradation and remodeling of extracellular matrix proteins.
      The activity of MMPs is tightly regulated at several levels including cleavage of
      prodomain, allosteric activation, compartmentalization and complex formation with
      tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system
      (CNS), MMPs play a wide variety of roles ranging from brain development, synaptic
      plasticity and repair after injury to the pathogenesis of various brain
      disorders. Following general discussion on the domain structure and the
      regulation of activity of MMPs, we emphasize their implication in various brain
      disorder conditions such as Alzheimer's disease, multiple sclerosis,
      ischemia/reperfusion and Parkinson's disease. We further highlight accumulating
      evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them,
      MMP-3 appears to be involved in a range of pathogenesis processes in PD including
      neuroinflammation, apoptosis and degradation of alpha-synuclein and DJ-1. MMP
      inhibitors could represent potential novel therapeutic strategies for treatments
      of neurodegenerative diseases. 

PMID- 24116288
TI  - Effects of docosahexaenoic Acid on neurotransmission.
AB  - Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the
      brain and a structural component of neuronal membranes. Changes in DHA content of
      neuronal membranes lead to functional changes in the activity of receptors and
      other proteins which might be associated with synaptic function. Accumulating
      evidence suggests the beneficial effects of dietary DHA supplementation on
      neurotransmission. This article reviews the beneficial effects of DHA on the
      brain; uptake, incorporation and release of DHA at synapses, effects of DHA on
      synapses, effects of DHA on neurotransmitters, DHA metabolites, and changes in
      DHA with age. Further studies to better understand the metabolome of DHA could
      result in more effective use of this molecule for treatment of neurodegenerative
      or neuropsychiatric diseases. 

PMID- 24116289
TI  - Phloroglucinol Inhibits the in vitro Differentiation Potential of CD34 Positive
      Cells into Endothelial Progenitor Cells.
AB  - Inhibiting the bioactivities of circulating endothelial progenitor cells (EPCs)
      results in significant inhibition of neovessel formation during tumor
      angiogenesis. To investigate the potential effect of phloroglucinol as an EPC
      inhibitor, we performed several in vitro functional assays using CD34(+) cells
      isolated from human umbilical cord blood (HUCB). Although a high treatment dose
      of phloroglucinol did not show any cell toxicity, it specifically induced the
      cell death of EPCs under serum free conditions through apoptosis. In the EPC
      colony-forming assay (EPC-CFA), we observed a significant decreased in the small
      EPC-CFUs for the phloroglucinol group, implying that phloroglucinol inhibited the
      early stage of EPC commitment. In addition, in the in vitro expansion assay using
      CD34(+) cells, treatment with phloroglucinol was shown to inhibit endothelial
      lineage commitment, as demonstrated by the decrease in endothelial surface
      markers of EPCs including CD34(+), CD34(+)/CD133(+), CD34(+)/CD31(+) and
      CD34(+)/CXCR4(+). This is the first report to demonstrate that phloroglucinol can
      inhibit the functional bioactivities of EPCs, indicating that phloroglucinol may
      be used as an EPC inhibitor in the development of biosafe anti-tumor drugs that
      target tumor angiogenesis. 

PMID- 24116290
TI  - Mouse Melanoma Cell Migration is Dependent on Production of Reactive Oxygen
      Species under Normoxia Condition.
AB  - Cell migration plays a role in many physiological and pathological processes.
      Reactive oxygen species (ROS) produced in mammalian cells influence intracellular
      signaling processes which in turn regulate various biological activities. Here,
      we investigated whether melanoma cell migration could be controlled by ROS
      production under normoxia condition. Cell migration was measured by wound healing
      assay after scratching confluent monolayer of B16F10 mouse melanoma cells. Cell
      migration was enhanced over 12 h after scratching cells. In addition, we found
      that ROS production was increased by scratching cells. ERK phosphorylation was
      also increased by scratching cells but it was decreased by the treatment with ROS
      scavengers, N-acetylcysteine (NAC). Tumor cell migration was inhibited by the
      treatment with PD98059, ERK inhibitor, NAC or DPI, well-known ROS scavengers.
      Tumor cell growth as judged by succinate dehydrogenase activity was inhibited by
      NAC treatment. When mice were intraperitoneally administered with NAC, the
      intracellular ROS production was reduced in peripheral blood mononuclear cells.
      In addition, B16F10 tumor growth was significantly inhibited by in vivo treatment
      with NAC. Collectively, these findings suggest that tumor cell migration and
      growth could be controlled by ROS production and its downstream signaling
      pathways, in vitro and in vivo. 

PMID- 24116291
TI  - HaCaT Keratinocytes and Primary Epidermal Keratinocytes Have Different
      Transcriptional Profiles of Cornified Envelope-Associated Genes to T Helper Cell
      Cytokines.
AB  - HaCaT cells are the immortalized human keratinocytes and have been extensively
      used to study the epidermal homeostasis and its pathophysiology. T helper cells
      play a role in various chronic dermatological conditions and they can affect skin
      barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell
      system to study abnormal skin barrier development in various dermatologic
      diseases, we analyzed the gene expression profile of epidermal differentiation
      markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as
      IFNgamma, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified
      envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin
      10 (KRT10), in HaCaT cells was generally different from that in normal human
      keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model
      system to study the pathophysiological mechanism associated with the Th cell
      cytokine-dependent changes in cornified envelope-associated proteins which are
      essential for normal skin barrier development. In contrast, the gene
      transcription profile change of human beta2-defensin (HBD2) in response to
      IFNgamma, IL-4 or IL-17A in HaCaT cells was consistent with the expression
      pattern of NHKs. IFNgamma also up-regulated transglutaminase 2 (TGM2) gene
      transcription in both HaCaT cells and NHKs. As an alternative cell culture system
      for NHKs, HaCaT cells can be used to study molecular mechanisms associated with
      abnormal HBD2 and TGM2 expression in response to IFNgamma, IL-4 or IL-17A. 

PMID- 24116292
TI  - Tetrazolium violet induced apoptosis and cell cycle arrest in human lung cancer
      a549 cells.
AB  - Tetrazolium violet is a tetrazolium salt and has been proposed as an antitumor
      agent. In this study, we reported for the first time that tetrazolium violet not
      only inhibited human lung cancer A549 cell proliferation but also induced
      apoptosis and blocked cell cycle progression in the G1 phase. The results showed
      that tetrazolium violet significantly decreased the viability of A549 cells at 5
      15 MUM. Tetrazolium violet -induced apoptosis in A549 cells was confirmed by
      H33258 staining assay. In A549, tetrazolium violet blocked the progression of the
      cell cycle at G1 phase by inducing p53 expression and further up-regulating
      p21/WAF1 expression. In addition, an enhancement in Fas/APO-1 and its two forms
      of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as
      well as caspase, were responsible for the apoptotic effect induced by tetrazolium
      violet. The conclusion of this study is that tetrazolium violet induced p53
      expression which caused cell cycle arrest and apoptosis. These findings suggest
      that tetrazolium violet has strong potential for development as an agent for
      treatment lung cancer. 

PMID- 24116293
TI  - Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia.
AB  - In this study, we examined the estrogenic activity of bavachin, a component of
      Psoralea corylifolia that has been used as a traditional medicine in Asia.
      Bavachin was purified from ethanolic extract of Psoralea corylifolia and
      characterized its estrogenic activity by ligand binding, reporter gene
      activation, and endogenous estrogen receptor (ER) target gene regulation.
      Bavachin showed ER ligand binding activity in competitive displacement of [(3)H]
      E2 from recombinant ER. The estrogenic activity of bavachin was characterized in
      a transient transfection system using ERalpha or ERbeta and estrogen-responsive
      luciferase plasmids in CV-1 cells with an EC50 of 320 nM and 680 nM,
      respectively. Bavachin increased the mRNA levels of estrogen-responsive genes
      such as pS2 and PR, and decreased the protein level of ERalpha by proteasomal
      pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells
      transiently transfected with the corresponding receptor and hormone responsive
      reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen
      by binding and activating the ER. 

PMID- 24116295
TI  - Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of
      Lymphoproliferative Response in vitro.
AB  - Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was
      investigated in splenocyte cultures. Following an incubation of arbutin with 5
      different intestinal bacteria for 24 hr, its aglycone hydroquinone could be
      produced and detected in the bacterial culture media with different amounts.
      Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative
      response were tested in splenocyte cultures from normal mice. Lipopolysaccharide
      and concanavalin A were used as mitogens for B- and T-cells, respectively. When
      bacteria cultured medium with arbutin was treated into the splenocytes for 3
      days, the medium cultured with bacteria producing large amounts of hydroquinone
      induced suppression of lymphoproliferative responses, indicating that metabolic
      activation by intestinal bacteria might be required in arbutin-induced toxicity.
      The results indicated that the present testing system might be applied for
      determining the possible role of metabolism by intestinal bacteria in certain
      chemical-induced immunotoxicity in animal cell cultures. 

PMID- 24116294
TI  - Peripubertal administration of icariin and icaritin advances pubertal development
      in female rats.
AB  - Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts
      estrogenic activity. In this study, we investigated the effect of peripubertal
      administration of Epimedii Herba on pubertal development in female rats using a
      modified protocol of the rodent 20-day pubertal female assay. Female Sprague
      Dawley rats (21 days old after weaning, 10 rats per group) were divided into five
      groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin
      (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by
      subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to
      vaginal opening (VO) was shorter for the Epimedii groups, particularly for the
      ICT group (p<0.05). Treatment with ICI and ICT significantly increased the
      duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days).
      Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT
      treatments while the weight of the uterus and pituitary glands increased
      significantly only in the E2 and ICT groups. Although Epimedii Herba displayed
      relatively weak estrogenic activity, its repeated administration could affect
      pubertal development in female rats. 

PMID- 24116296
TI  - Photoprotective Potential of Anthocyanins Isolated from Acanthopanax divaricatus
      Var. albeofructus Fruits against UV Irradiation in Human Dermal Fibroblast Cells.
AB  - Ultraviolet (UV) A penetrates deeply into the skin and induces the generation of
      reactive oxygen species (ROS) causing damage to fibroblasts, which leads to aging
      of the skin. However, the body has developed an antioxidant defence system
      against the harmful effects of ROS. Enzymes such as superoxide dismutase (SOD)
      and catalase (CAT) play critical roles on the removal of excess ROS in living
      organisms. In this study, the antioxidant activities of anthocyanins (cyanidin 3
      galactoside and cyanidin 3-lathyroside) from Acanthopanax divaricatus var.
      albeofructus (ADA) fruits were investigated by xylenol orange, thiobarbituric
      acid reactive substances (TBARS), and antioxidant enzyme assay. As a result,
      generation of H2O2 and lipid peroxide induced by UVA-irradiation in human dermal
      fibroblast (HDF-N) cells was reduced by treatment of anthocyanins. Also,
      augmented enzyme (SOD and CAT) activities were observed in UVA-irradiated cells
      when treated with anthocyanin. In conclusion, the results obtained show that
      anthocyanins from ADA fruits are potential candidates for the protection of
      fibroblast against the damaging effects of UVA irradiation. Furthermore,
      anthocyanin may be a good candidate for antioxidant agent development. 

PMID- 24116297
TI  - Krill-Derived Phosphatidylserine Improves TMT-Induced Memory Impairment in the
      Rat.
AB  - The present study examined the effects of krill-derived phosphatidylserine (Krill
      PS) on the learning and memory function and the neural activity in rats with
      trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle
      (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21
      days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats
      was investigated by assessing the Morris water maze test and by performing
      choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive
      element binding protein (CREB) immunohistochemistry. The rats with TMT injection
      showed impaired learning and memory of the tasks and treatment with Krill-PS
      produced a significant improvement of the escape latency to find the platform in
      the Morris water maze at the 2(nd) and 4(th) day compared to that of the MCT
      group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased
      time spent around the platform compared to that of the MCT group. Consistent with
      the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of
      acetylcholinergic neurons in the hippocampus and medial septum compared to that
      of the MCT group. Treatment with Krill-PS significantly increased the CREB
      positive neurons in the hippocampal CA1 area as compared to that of the MCT
      group. These results suggest that Krill-PS may be useful for improving the
      cognitive function via regulation of cholinergic marker enzyme activity and
      neural activity. 

PMID- 24116298
TI  - Monoamine Oxidase and Dopamine beta-Hydroxylase Inhibitors from the Fruits of
      Gardenia jasminoides.
AB  - This research was designed to determine what components of Gardenia jasminoides
      play a major role in inhibiting the enzymes related antidepressant activity of
      this plant. In our previous research, the ethyl acetate fraction of G.
      jasminosides fruits inhibited the activities of both monoamine oxidase-A (MAO-A)
      and monoamine oxidase-B (MAO-B), and oral administration of the ethanolic extract
      slightly increased serotonin concentrations in the brain tissues of rats and
      decreased MAO-B activity. In addition, we found through in vitro screening test
      that the ethyl acetate fraction showed modest inhibitory activity on dopamine
      beta hydroxylase (DBH). The bioassay-guided fractionation led to the isolation of
      five bio-active compounds, protocatechuic acid (1), geniposide (2), 6'-O-trans-p
      coumaroylgeniposide (3), 3,5-d-ihydroxy-1,7-bis (4-hydroxyphenyl) heptanes (4),
      and ursolic acid (5), from the ethyl acetate fraction of G. jasminoides fruits.
      The isolated compounds showed different inhibitory potentials against MAO-A, -B,
      and DBH. Protocatechuic acid showed potent inhibition against MAO-B (IC50 300
      MUmol/L) and DBH (334 MUmol/L), exhibiting weak MAO-A inhibition (2.41 mmol/L).
      Two iridoid glycosides, geniposide (223 MUmol/L) and 6'-O-trans-p
      coumaroylgeniposide (127MUmol/L), were selective MAO-B inhibitor. Especially, 6'
      O-trans-p-coumaroylgeniposide exhibited more selective MAO-B inhibition than
      deprenyl, well-known MAO-B inhibitor for the treatment of early-stage Parkinson's
      disease. The inhibitory activity of 3,5-di-hydroxy-1,7-bis (4-hydroxyphenyl)
      heptane was strong for MAO-B (196 MUmol/L), modest for MAO-A (400 MUmol/L), and
      weak for DBH (941 MUmol/L). Ursolic acid exhibited significant inhibition of DBH
      (214 MUmol/L), weak inhibition of MAO-B (780 MUmol/L), and no inhibition against
      MAO-A. Consequently, G. jasminoides fruits are considerable for development of
      biofunctional food materials for the combination treatment of depression and
      neurodegenerative disorders. 

PMID- 24116299
TI  - Pectinase-Processed Ginseng Radix (GINST) Ameliorates Hyperglycemia and
      Hyperlipidemia in High Fat Diet-Fed ICR Mice.
AB  - To develop a ginseng product possessing an efficacy for diabetes, ginseng radix
      ethanol extract was treated with pectinase and obtained the GINST. In the present
      study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced
      hyper-glycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice
      were randomly divided into five groups: regular diet group (RD), high fat diet
      group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300
      mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the
      glucose tolerance after glucose challenge. Fasting plasma glucose and insulin
      levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150,
      and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin
      resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in
      GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma
      triglyceride, total cholesterol and non-esterified fatty acid levels in the
      GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared
      to those in HFD control group. Enlarged adipocytes of HFD control group were
      markedly decreased in GINST-treated groups, and shrunken islets of HFD control
      mice were brought back to near normal shape in GINST300 group. Furthermore, GINST
      enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose
      transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and
      hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4
      pathways, and could be a potential therapeutic agent for type 2 diabetes. 

PMID- 24116300
TI  - Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague
      Dawley Rat Offsprings.
AB  - Ethanol exposure during gestational period is related to growth retardation,
      morphological abnormality, and even in neurological abnormalities including
      attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring.
      However, relatively little is known about the effects of maternal ethanol
      consumption prior to conception on their offspring. In this study, we investi
      gated whether maternal ethanol administration during preconceptional phase
      produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female
      rats were administrated ethanol via intragastric intubation with dosing regimen
      of 6 g/kg daily for 10 consecutive days and treated female rats then mated with
      non-treated male SD rats after 8 weeks. Another group subjected to the same
      procedure as those conducted on ethanol treated group except the saline
      administration instead of ethanol. Offspring was tested for their ADHD-like
      behaviors using open field test, Y maze test and impulsivity test that is
      performed in the aversive electronic foot shock paradigm. Offspring of
      preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity,
      attention deficit and impulsivity. And reduction of striatal dopamine transporter
      (DAT) level was observed by Western blot in the EtOH group, compared to control
      (Con) group, while the immunohistochemical analysis exhibited increased
      expression of norepinephrine transporter (NET) in the frontal cortex. These
      results suggest that maternal ethanol consumption in the preconceptional phase
      induces ADHD-like behaviors in offspring that might be related to the abnormal
      expression of DAT and NET in rat. 

PMID- 24116301
TI  - Dependence potential of propofol: behavioral pharmacology in rodents.
AB  - Propofol is an anesthetic commonly used to provide sedation or to induce and
      maintain an anesthetic stated. However, there are reports which indicate propofol
      may cause psychological dependence or be abused. In the present study, we used
      various behavioral tests including climbing test, jumping test, conditioned place
      preference, and self-administration test to assess the dependence potential and
      abuse liability of propofol compared to a positive control (methamphetamine) or a
      negative control (saline or intralipid). Among the tests, the conditioned place
      preference test was conducted with a biased method, and the selfadministration
      test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No
      difference was found in the climbing test and jumping test, but propofol (30
      mg/kg, i.p.) increased the rewarding effect in the conditioned place preference
      test, and it showed a positive reinforcing effect compared to the vehicle. These
      results indicate that propofol tends to show psychological dependence rather than
      physical dependence, and it seems not to be related with dopaminergic system. 

PMID- 24116302
TI  - Inhibitory Effects of 4-Guanidinobutyric Acid against Gastric Lesions.
AB  - This study examined the inhibitory effects of 4-guanidinobutyric acid (4GBA), an
      alkaloid, against gastric lesions by assessing the inhibition of Helicobacter
      pylori (H. pylori) and gastric cancer cells. Acute and chronic gastritis were
      also observed using HCl/ethanol (EtOH) and indomethacin-induced gastric lesion
      models, respectively. 4GBA inhibited the growth of H. pylori in a dose dependent
      manner, and showed acid-neutralizing capacity. In the pylorus ligated rats, 4GBA
      decreased the volume of gastric secretion and gastric acid output slightly, and
      increased the pH. 4GBA at a dose of 100 mg/kg reduced the size of HCl/EtOH
      induced gastric lesions (70.8%) and indomethacin-induced gastric lesions (38.8%).
      The antigastritic action of 4GBA might be associated with the acid-neutralizing
      capacity, anti-H. pylori action, and decreased volume of gastric secretion. These
      results suggest that 4GBA might be useful in the treatment and/or protection of
      gastritis. 

PMID- 24116303
TI  - Revisiting public health challenges in the new millennium.
AB  - Positive Health of the communities could only be brought out through the
      interrelationship between conventional health sector and other development
      sectors. It was a dream that came true when World Health Organization (WHO)
      accepted Primary Health Care (PHC) as the major tool to achieve its proposed goal
      of Health For All (HFA) by 2000 A.D., but we could not succeed as expected. Now
      we have the Millennium Development Goals (MDG), which place health at the heart
      of development but the achievements in health is still challenging. The
      literature search in this article has been conducted in Pub Med and Google
      scholar, with the aim to draw references to discuss the major health issues and
      ways to tackle them. The current article briefly narrates the burden and
      complexities of challenges faced by the present global health. Revisiting the
      concept of PHC and reaffirming our solidarity to this philosophy is the need of
      this hour. 

PMID- 24116304
TI  - Are the currently existing anti-human papillomavirus vaccines appropriate for the
      developing world?
AB  - Cervical cancer prevention is expected to be achieved by vaccination of girls 2-3
      years before sexual debut, and cervical smear cytology follow-up. The existing
      human papillomavirus (HPV) vaccines target the low-risk 6 and 11, and the high
      risk 16 and 18 subtypes, the most common agents of ano-genital pre-invasive and
      invasive lesions. We conducted the review by searching PubMed using the terms
      "HPV," "HPV subtypes," "developing world," and "HPV-vaccine" to retrieve articles
      published between 2000 and 2011. We focused on studies that were relevant to the
      developing world. The proposed vaccination policy is currently unachievable in
      the developing world because of the cost of the vaccine, the lack of adequate
      cytology and follow-up infrastructures. Moreover, the subtypes of HPV involved in
      cervical pathology, their associations, and natural history (clearance and
      persistence rates) differ from the industrialized world. Therefore, the current
      bivalent and quadrivalent anti-HPV vaccines are unlikely to achieve their target
      in the developing world. It follows from published data that there is an
      obligation of the pharmaceutical industry and of the public-health policy makers
      not to embark on mass vaccination campaigns without thorough information and
      investigation of the local relevance. 

PMID- 24116305
TI  - Peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is a rare form of unexplained cardiac failure of
      unknown origin, unique to the pregnant woman with highly variable outcome
      associated with high morbidity and mortality. PPCM is fraught with controversies
      in its definition, epidemiology, pathophysiology, diagnosis and management. PPCM
      is frequently under diagnosed, inadequately treated and without a laid down
      follow-up regimen, thus, the aim of this review. Publications on PPCM were
      accessed using Medline, Google scholar and Pubmed databases. Relevant materials
      on PPCM, selected references from internet services, journals, textbooks, and
      lecture notes on PPCM were also accessed and critically reviewed. PPCM is
      multifactorial in origin. It is a diagnosis of exclusion and should be based on
      classic echocardiographic criteria. The outcome of PPCM is also highly variable
      with high morbidity and mortality rates. Future pregnancies are not recommended
      in women with persistent ventricular dysfunction because the heart cannot
      tolerate increased cardiovascular workload associated with the pregnancy.
      Although, multiparity is associated with PPCM, there is an increased risk of
      fetal prematurity and fetal loss. PPCM is a rare form of dilated cardiomyopathy
      of unknown origin, unique to pregnant women. The pathophysiology is poorly
      understood. Echocardiography is central to diagnosis of PPCM and effective
      treatment monitoring in patients of PPCM. The outcome is highly variable and
      related to reversal of ventricular dysfunction. 

PMID- 24116306
TI  - Oral health and menopause: a comprehensive review on current knowledge and
      associated dental management.
AB  - The menopause is physiological changes in women that give rise to adaptive
      changes at both systemic and oral level. As we all begin to reach an older age,
      dental health and hygiene becomes a major concern. The dentist is often the first
      person to appreciate numerous changes that are experienced throughout the body
      during menopause. The teeth and gums are extremely susceptible to any hormonal
      changes that take place just before menopause and readily decrease body's ability
      to fight off minor infections or maintain a healthy balance of useful and harmful
      bacteria within the oral environment. This review aimed to develop better
      understanding for major oro-dental complications observed in women during
      menopause, and schematic approach towards the different dental management
      protocols used during these periods. Various internets based popular search
      engines were used to explore related data from literature, which includes PubMed,
      PubMed Central, Cochrane, Google, Medknow, Ebsco, Science Direct, and IndMed.
      Upon compilation of relevant data, it was observed that periodontal health is
      most severely affected (up to 60%) followed by dry mouth (25%) and burning mouth
      (glossodynia; 15%) which, in turn, may increase the occurrence of oral mucosal
      and dental diseases, such as candidiasis. Though, the usage of hormone
      replacement therapy is effective but it does not necessarily prevent or help
      women with oral symptoms. Therefore, well controlled long-term randomized studies
      are needed to establish more authentic clinical guidelines for successful
      management of such conditions. 

PMID- 24116307
TI  - Challenges in the management of bronchial asthma among adults in Nigeria: a
      systematic review.
AB  - Inadequate attention given to the management of asthma and ways of improving
      bronchial asthma control could be an important factor for the rising morbidity
      and mortality from asthma despite major advances in our understanding of the
      disease process. There is a paucity of data concerning the challenges faced in
      the management of asthma in Africa. This review was aimed at highlighting the
      challenges facing asthma management and to discuss various strategies in
      improving asthma control in Nigeria. Data were sourced from PubMed, Medline,
      African Journals Online, Google Scholar, SCOPUS, and by reviewing the references
      of relevant literature. Additional articles were obtained via communications with
      colleagues and reviewing the Abstract Books of Nigeria Thoracic Society Annual
      Scientific Conference from 2005 to 2012. The data search was up-to-date as of
      December 31, 2012. Challenges in asthma management were found during diagnosis,
      treatment, and follow-up. There are wide variations in diagnostic criteria for
      bronchial asthma and lack of standard diagnostic equipment leading to under or
      misdiagnosis. Treatment challenges include poor communication gap between the
      health-care providers and the patients, a high-cost and unavailability of
      essential asthma medications. Poor technique uses for medication devices,
      especially the inhalational drugs and Lack of National/hospital protocol or
      guidelines for treating asthma. Several challenges affect asthma management in
      developing countries, which borders on poverty, inadequate resources, weak health
      systems, and poor infrastructure. Efforts should be made to address these
      challenges by the Nigerian government, Nigerian Thoracic Society, pharmaceutical
      industries, and the health-care workers in general. 

PMID- 24116308
TI  - Sonographic evaluation of the splenic length in normal pregnancy in a tertiary
      hospital in southern Nigeria: a pilot study.
AB  - BACKGROUND: The spleen is affected by the changes that occur in pregnancy.
      Ultrasound is the commonest imaging modality used in the evaluation of the
      abdominal organs in pregnancy; however, there is a paucity of information on the
      sonographic measurement of the splenic length in normal pregnancy in our
      environment. AIM: To establish sonographically the range of splenic length in
      normal pregnant women. SUBJECTS AND METHODS: A prospective descriptive cross
      sectional study of the sonographic measurements of the splenic length was
      performed on 150 healthy normal pregnant women correlating this with the body
      mass index, gestational age and parity. Data were analyzed using software SPSS
      version 15 (SPSS Inc., Chicago, IL, USA). Correlations and variance between
      variables were calculated. P values 0.05 were considered as significant. RESULTS:
      A mean splenic length of 10.0 cm (SD) 1.8 throughout pregnancy was obtained with
      a range of 9.7-10.3 cm. The splenic length significantly correlated positively
      with the body mass index (r = 0.006, P < 0.01) but not with parity (r = 0.94, P <
      0.01), and gestational age (r = 0.31, P < 0.01). CONCLUSION: This study was able
      to establish a range of sonographic measurement of the splenic length for the
      locality.

PMID- 24116309
TI  - A Two Wave Analysis of Hospitalizations and Mortality from Seasonal and Pandemic
      2009 A (H1N1) Influenza in Saurashtra, India: 2009-2011.
AB  - BACKGROUND: During May 2009, India reported the confirmed case of 2009 A (H1N1)
      influenza reported and in August 2009, Saurashtra region made the first report.
      AIM: We describe the clinico-epidemiological characteristics of patients who were
      hospitalized with 2009 A (H1N1) influenza infection and seasonal influenza in
      Saurashtra region. SUBJECTS AND METHODS: A total of 1726 patients suffering from
      A (H1N1) influenza and seasonal influenza were admitted in the different
      hospitals of Rajkot city of Saurashtra region during September 2009-February
      2011. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing
      was used to confirm the infection. The clinico-epidemiological features of the
      patients were closely monitored. Data were analyzed by Chi square or Fisher's
      exact test, using Epi Info software (version 3.5.1) of the Center for Disease
      Control (CDC). RESULTS: Among the patients hospitalized due to influenza, 29.6%
      (511/1726) were laboratory confirmed cases of A (H1N1) influenza while the rest
      70.4% (1215/1726) were cases of seasonal influenza. A median time of 5 days was
      observed from the onset of illness to laboratory confirmed diagnosis of A (H1N1)
      influenza. The median duration of hospital stay of such patients was 2-32 days.
      All admitted A (H1N1) influenza patients received Oseltamivir drug, but only
      14.9% (76/511) received it within 2 days of onset of illness. 24.9% (127/511) of
      those admitted for A (H1N1) influenza died as compared to 5.3% (65/1215) of those
      suffering from seasonal influenza. The most common symptoms were cough, fever,
      sore throat and shortness of breath in both the groups of patients. The
      prevalence of any coexisting morbidity in those with A (H1N1) influenza was 31.3%
      (160/511) while in those with seasonal influenza it was 19.4% (236/1215). The
      common coexisting morbidities were hypertension, diabetes mellitus, chronic
      pulmonary diseases and pregnancy. Pneumonia was reported in 91% positive patients
      with chest radiography. CONCLUSION: Though the clinico-epidemiological pattern of
      the A (H1N1) influenza patients were comparable to that of those suffering from
      seasonal influenza, a fivefold higher mortality was noted in A (H1N1) influenza
      patients. Hypertension, pregnancy, pneumonia on chest X-ray, and receiving
      antiviral treatment within 2 days of illness onset were mainly reported among A
      (H1N1) influenza patients.

PMID- 24116310
TI  - Yoga for high-risk pregnancy: a randomized controlled trial.
AB  - BACKGROUND: Improvements in technology have increased the chances of survival for
      the micro-premature infant and the very low birth-weight infant but have
      significantly increased the financial burden of health care organizations. This
      economic burden has a significant impact on third-party payers and on society in
      general. AIM: The study was designed to assess yoga therapy (YT) module on
      maternal stress level in high risk pregnancy. SUBJECTS AND METHODS: In the
      present study, sixty-eight pregnant women (38 in the control group with standard
      antenatal care and 30 in the YT group) with 27.2 (5.2) years of mean age
      recruited from the outpatient services of medical college and hospital in
      Bangalore, South India, were participated. The study was a single-blind
      randomized controlled clinical trial. Perceived stress scale (PSS) was measured
      during the 12(th), 20(th), and 28(th) weeks of pregnancy. SPSS version 16.0
      (Chicago, IL, USA) was used for all data analysis. When the data were found to be
      normally distributed, the RMANOVA were used to assess the PSS scores between the
      yoga and control groups. Significant values were set at P < 0.05. RESULTS: There
      was a significant difference in the PSS level of the YT group with significantly
      reduced scores at the second follow-up (28(th) week of pregnancy) compared to the
      control group (P = 0.02). Women who took part in the YT module reported
      significantly fewer pregnancy discomforts decrease in PSS (P = 0.02) than the
      control group where the stress level was increased (RMANOVA test using SPSS-16).
      CONCLUSION: The present study suggests that the YT module can decrease the stress
      level during high-risk pregnancy complications. Thus, practicing YT during high
      risk pregnancy is not only a cost-effective option but also a feasible and safe
      option. Additional well-designed studies are needed before a strong
      recommendation can be made.

PMID- 24116311
TI  - The frequency and pattern of female genital tract malignancies at the university
      of Nigeria teaching hospital, enugu, Nigeria.
AB  - BACKGROUND: Female genital tract malignancy is common in our low resource
      setting. Options now exist for prevention, detection, treatment, and palliative
      care for the wide spectrum of female genital tract malignancies. Women will
      continue to die from these cancers unless health professionals and civil society
      adopt means to control female genital tract cancers in our low resource setting.
      AIM: The objective was to determine the frequency and patterns of female genital
      tract malignancy at the University of Nigeria Teaching Hospital (UNTH), Enugu,
      Nigeria. MATERIALS AND METHODS: A 6-year retrospective study of female genital
      tract malignancies was conducted at the UNTH, Enugu. The case notes of patients
      admitted for female genital tract malignancy between January 1, 2003 and December
      31, 2008 were retrieved from the medical records and cancer registry of the
      University of Nigeria Teaching Hospital, Enugu and relevant data were extracted.
      The data were analyzed using SPSS version 12 (SPSS Inc., Chicago, IL, USA) and
      the results expressed in descriptive statistics by simple percentages. RESULTS:
      One hundred and sixty six (166) cases of genital malignancies were recorded
      during the 6-year review. Majority of the patients were in the fifth and sixth
      decades of life. Cancer of the cervix accounted for 66.3% (110/166) followed by
      ovarian cancer 21.1% (35/166). The other tumors seen during the period were
      tumors involving corpus uteri 9% (15/166) and vulva 3.6% (6/166). Tumors of
      fallopian tube and vagina were not seen during the study period. CONCLUSION:
      Despite the preventable nature of cancer of cervix, it remained the most common
      female genital tract malignancy in Enugu, South-East Nigeria. In our low resource
      setting in the developing countries, education and public enlightenment on the
      importance of routine screening and treatment of premalignant lesions of the
      cervix are necessary tools to reduce the incidence and mortality of cervical
      cancer.

PMID- 24116312
TI  - Prevalence of hand disorders in type 2 diabetes mellitus and its correlation with
      microvascular complications.
AB  - BACKGROUND: Physicians have long recognized the association between diabetes
      mellitus and several pathologic conditions of the hand. The most commonly
      recognized maladies are limited joint mobility (LJM), Dupuytren's disease (DD),
      trigger finger (TF), and carpal tunnel syndrome (CTS). Incidence of these hand
      disorders has increased in the setting of diabetes. Collectively, these are
      described as diabetic hand syndrome. AIM: The aims were to find out the
      prevalence of hand disorders in diabetic patients, and to study the relation of
      these hand disorders with microvascular complications. SUBJECTS AND METHODS: This
      is an observational cross-sectional case-control study done over a period of 1
      year Patients of type 2 DM, of age < 65 years, who visited Gandhi Memorial
      Hospital, Lucknow were enrolled and were described as cases. Age- and sex-matched
      nondiabetic individuals were taken in the control group. The data were analyzed
      using software SPSS. SPSS Inc. Released 2008. SPSS Statistics for Windows,
      Version 17.0. Chicago: SPSS Inc. Means and standard deviations were computed; the
      Student t-test and Chi-square (chi(2)) test were used as appropriate. RESULTS: A
      total of 400 subjects were studied, 200 each in the case and control groups. Of
      total 200 diabetic patients, 30% (60/200) patients had neuropathy, 37.5% (75/200)
      had nephropathy, and 44.5% (89/200) patients had retinopathy. In the study
      population, 67% patients were having one or more hand disorders, in which LJM was
      found in 40.5% (81/200) patients, DD was found in 19% (38/200) patients, TF in
      16.5% (33/200), and CTS in 14% (28/200) patients. CONCLUSIONS: This study shows a
      high prevalence of hand disorders in diabetic patients and also correlates with
      the duration of type 2 DM, LJM being the most common hand disorder and more
      common in patients who have microvascular complications.

PMID- 24116313
TI  - Smoking prevalence and attitudes regarding its control among health professional
      students in South-Western Nigeria.
AB  - BACKGROUND: Tobacco use is one of the leading preventable causes of morbidity and
      mortality globally; about 70% of smokers see physicians each year. Health care
      professionals have a very unique role in motivating people to quit smoking. AIM:
      The aims of this study were to document the smoking prevalence and attitudes
      regarding its control among these set of students who will be tomorrow's health
      care providers. SUBJECTS AND METHODS: A cross-sectional survey was conducted in
      two medical schools in South-Western Nigeria with their accompanied nursing and
      pharmacy students. All students in the selected schools were eligible to
      participate and student's participation was voluntary. The Global Health
      Professional Students Survey core questionnaire was used to collect data on
      smoking prevalence and attitudes regarding its control. The data were summarized
      using percentages and confidence interval (CI) was calculated using standard
      error of mean. Pearson's Chi-square and fisher's exact were employed to test the
      significance. RESULTS: Life-time prevalence of cigarette smoking was 17.9%
      (121/675) with (95% confidence interval [CI] 15-20.8). Only 5.04% (34/675) with
      (95% CI 3.7-7.1) of the respondents were currently smoking. Ever smokers were
      significantly less likely than non-smokers to indicate that tobacco sales to
      adolescents should be banned (P < 0.01). Fewer smokers than non-smokers agreed
      that there should be a complete ban on advertising of tobacco products (P <
      0.001). 93.3% of them said that they were taught about danger of smoking but only
      48.6% ever heard of using anti-depressant in tobacco cessation program.
      CONCLUSIONS: Smoking prevalence among health professional students in South-West
      Nigeria is relatively low; however, majority believed that health-care providers
      serve as role models for their patients and the public.

PMID- 24116314
TI  - Clinical features of acute gastroenteritis in children at university of Nigeria
      teaching hospital, ituku-ozalla, enugu.
AB  - BACKGROUND: Acute gastroenteritis (AGE) is a major cause of morbidity and
      mortality in children world-wide with the highest incidence in the developing
      countries. The persistence and effect of this condition require a study of the
      features and characteristics of the disease especially, within any (each)
      locality in order to offer possible control solutions. AIM: To determine, the
      clinical and social characteristics associated with AGE among children seen in
      the University of Nigeria Teaching Hospital, Enugu. SUBJECTS AND METHODS: A
      hospital-based population study in which children admitted in the children
      emergency room of the University of Nigeria Teaching Hospital whose
      parents/caregivers gave their consent were enrolled, over a 7 month period.
      Appropriate statistical tools: Chi-square, t-tests, correlation and logistic
      regression were used to determine significant values and associations. RESULTS: A
      total of 76 children with AGE were enrolled; 69.7% (53/76) were males. The mean
      age of the subjects was 11.3 (6.6) months. Majority 94.7%, (72/76) of cases of
      AGE occurred in children less than 24 months, with children 6-11 months
      contributing the highest percentage 42%, (32/76). The study population was
      predominantly urban dwellers; 78.9%, (60/76, P = 0.40) and water cistern
      constituted 77.6% (58/76) of waste disposal method. Those who had potable water
      supply were 23.7%, (18/76, P = 0.30) and 19.7% of the children were exclusively
      breast fed. Fever and vomiting were the commonest associated symptoms, occurring
      in 82.9% (63/76) and 73.7% (56/76) of the subjects respectively. A good
      percentage of the subjects 64.5%, (49/76) had ORS before presentation.
      CONCLUSION: AGE is more common in older infants among those who were not
      exclusively breast-fed and the severity was unrelated to place of domicile and
      waste disposal habits.

PMID- 24116315
TI  - The role of complications of community acquired pneumonia on the outcome of the
      illness: a prospective observational study in a tertiary institution in eastern
      Nigeria.
AB  - BACKGROUND: Community acquired pneumonia (CAP) is a major cause of mortality and
      morbidity in our environment. Recent data on the role of complications on outcome
      of CAP are not readily available in Nigeria. AIM: This study aims to analyze the
      influence of complications on the outcome of CAP in a tertiary health center in
      Eastern Nigeria. SUBJECTS AND METHODS: A prospective observational study was
      carried out on 80 patients with CAP, who met the inclusion criteria. Data
      relating to their age, gender, and clinical details; severity assessment using
      CURB 65 (C- confusion, Serum urea > 7mmol/L, R-respiratory rate > 30, B-systolic
      BP > 90 and diastolic BP <= 60, age > 65 years.) scoring system, laboratory
      results, complications, and outcome (mortality) were collected. The statistical
      package used for data analysis is SPSS version 17.0 (Chicago IL USA). Data were
      presented in tables and charts. Sample means, standard deviation, and Chi-square
      test were used for statistical significance. Severity was assessed using CURB65
      scoring system. Outcome of interest was 30 day mortality. In all P value of 0.05
      was regarded as significant. RESULTS: Eighty patients were recruited for the
      study, 39 males and 41 females; giving male:female ratio of 1:1.05. The mean age
      range was 56 (18.0) years. A total of 37 patients were managed as out-patients
      while 43 were managed as in-patients. Complications were observed in 25 patients.
      Severe hemodynamic changes and pleural effusion 8/25 (32%) were the most common
      complications observed. Total mortality was 12/80 (15%). Mortality was higher in
      in-patients than out-patients however, this was not statistically significant.
      Mortality in those with complications was 6/25 (24%) compared to 6/55 (11%) in
      those without complications (P = 0.10). CONCLUSION: Mortality rate in patients
      with CAP though higher in patients with complications numerically were not found
      to be significantly higher than in those without complications. We posit that
      other factors like presence of higher severity assessment scores (CURB-65 scores)
      and co-morbidities may be more important predictors of mortality in CAP patients
      and should be further studied.

PMID- 24116316
TI  - Infant and Young Child Feeding Perceptions and Practices among Mothers in a Rural
      Area of West Bengal, India.
AB  - BACKGROUND: There are many wrong practices and perceptions of Infant and Young
      Child Feeding (IYCF) prevalent among different socio-demographic groups. AIM: To
      observe IYCF perceptions and practices among mothers in a rural area of West
      Bengal. SUBJECTS AND METHODS: Clinic-based cross-sectional descriptive study by
      interviewing mothers of 0-23 month old children. Appropriate response to each
      selected key question was assigned a score of + 1 for objective assessment. Data
      analysis was done by standard statistical methods using the statistical software
      SPSS 13.0 (Kolkata, India) for windows version. Percentages were calculated for
      descriptive statistics. Chi-square test of significance was employed whenever
      required. RESULTS: 65.8% (225/342) mothers did not initiate breast feeding within
      1 h of birth, 41.7% (90/216) mothers of children aged 6 months or more did not
      exclusively breastfeed their babies up to 6 months and 28.1% (96/342) used
      bottles for baby-feeding. Perception scores among younger than 20-year-old
      mothers were found to be highest; however, practice score increased significantly
      with age. Though perception and practice of mothers with some education were
      significantly better they wane with higher education. Lowest practice score was
      found in the richest per capita income group. CONCLUSION: Emphasis should be
      given to IYCF education sessions.

PMID- 24116317
TI  - Common errors in manuscripts submitted to medical science journals.
AB  - BACKGROUND: Many manuscripts submitted to biomedical journals are rejected for
      reasons that include low-quality of the manuscripts. AIM: The aim of this study
      is to identify and characterize the common errors in manuscripts submitted to
      medical journals based in Africa and Asia. MATERIALS AND METHODS: Reviewers'
      reports on 42 manuscripts were analyzed qualitatively using deductive coding, and
      quantitatively to determine the errors by sections of the manuscripts. The study
      included only reviews on full length original research articles. RESULTS: Results
      showed that 66.7% (28/42) of the manuscripts had flaws in the introduction, 85.7%
      (36/42) in materials and methods, 66.7% (28/42) in the results, 71.4% (30/42) in
      discussion, 69.0% (29/42) in references, and 81.1% (34/42) in the general
      sections. Qualitative analysis of the reviews revealed 22 themes. Most common
      flaws identified were improper review of literature, provision of insufficient
      detailed methodology, unsystematic or illogical presentation of results, and
      unsupported conclusions. Others were inconsistent or nonconforming citations, and
      lack of good grammatical writing. CONCLUSIONS: The results show that many of the
      manuscripts had remarkable errors and demonstrate the need for attention to
      detail in study design and manuscript preparation and for further training of
      medical scientists in the techniques of manuscript writing for journal
      publication.

PMID- 24116318
TI  - HIV Risk Behavior in Persons with Severe Mental Disorders in a Psychiatric
      Hospital in Ogun, Nigeria.
AB  - BACKGROUND: Few studies in Nigeria have investigated HIV risk behavior among
      persons with severe mental disorders. This study examined HIV risk behavior and
      associated factors among patients receiving treatment at a Nigerian psychiatric
      hospital. AIM: To determine the HIV risk behavior in persons with severe mental
      disorders in a psychiatric hospital. SUBJECTS AND METHODS: This was a cross
      sectional survey involving 102 persons with serious mental disorders receiving
      treatment at a major psychiatric facility in Southwestern Nigeria. HIV risk
      screening instrument was self-administered to assess HIV risk behavior. A
      questionnaire was used to elicit socio-demographic variables while alcohol use
      was assessed with the alcohol use disorder identification test. Differences in
      HIV risk levels were examined for statistical significance using Chi square test.
      RESULTS: Forty eight percent of the respondents engaged in HIV risk behavior.
      This study revealed that 10.8% (11/102) gave a history of sexually transmitted
      disease, 5.9% (6/102) reported sex trading and no reports of intravenous drug use
      was obtained. A single risk factor was reported by 19.6% (20/102), 12.7% (13/102)
      reported two risk factors and 15.7% (16/102) reported three or more risk factors.
      HIV risk behavior was significantly related to alcohol use (P = 0.03).
      CONCLUSION: Mental health services provide an important context for HIV/AIDS
      interventions in resource-constrained countries like Nigeria.

PMID- 24116319
TI  - Slowly rising hilly young population of himachal: a step towards stabilization.
AB  - BACKGROUND: Socioeconomic development is the best contraceptive. Himachal Pradesh
      has made developments in all the fields, especially reducing the size of the
      family via family planning program. AIM: The objectives of this analysis are to
      describe the various methods of family planning used from 2003 to 2010 and their
      impact in averting the births in the state and in stabilizing the population.
      MATERIALS AND METHODS: We collected secondary data of the family planning program
      and the various methods employed from the total population (Census 2011) covered
      under family planning program (FPP) of the state. We analyzed and compared the
      results with India. We measured the impact of the program due to FP methods
      adopted. We employed the standardized program indicators- total fertility rate,
      birth rate, death rate, growth rate and census trend towards population growth;
      fertility rate (in %), birth rate and death rate (per thousand of the population
      per year) from 3.8, 31.5 and 11.1 in 1981 to 1.9, 17.2 and 7.2 in 2009. We
      entered dataset by double data entry technique and analyzed descriptively using
      Epi info version 3.3.2 and stat calc software. RESULTS: The state has the
      population of 6,856,509, sex ratio in age 0-6 years is 906/1000 males. The unmet
      need for family planning services is 15%. The impact of family planning program
      has resulted in averting of 3,387,744 of pregnancies from 2003 to 2010. The total
      fertility rate (TFR) has come down to 1.9 in 2008 from 3.8 children per woman in
      1981. The death rate has declined from 11.1 per 1000 live births in 1981 to 7.2
      per 1000 live births in 2009. The trend in decadal growth rate of the state is
      observable as 23.0% in 1971 while in 2011, it is 12.8%; more towards young
      population and for geriatric one as well but not exploding like India.
      CONCLUSION: Total population is on the increase with reference to the population
      of reproductive age bracket (15-49 years) and also geriatric population above 60
      steadily despite good social and health indicators. Bulging reproductive age
      group with mild upward shift of the geriatric population is the root cause for
      increasing population in hills of Himachal Pradesh.

PMID- 24116320
TI  - Effects of demographic factors, body mass index, alcohol drinking and smoking
      habits on irritable bowel syndrome: a case control study.
AB  - BACKGROUND: Irritable Bowel Syndrome (IBS) is a common functional
      gastrointestinal disorder. AIMS: To identify demographic factors in patients with
      IBS. SUBJECTS AND METHODS: One-hundred and fifty three IBS patients seen at
      Taleghani Hospital Gastroenterology Clinic and met the Rome III criteria and 163
      peoples who did not meet IBS criteria were consecutively enrolled. Both groups
      were asked to complete a self-rating questionnaire containing information, which
      included questions about age, sex, monthly income, education level, marital
      status, height, weight, alcohol drinking and smoking habits. Student's t-test,
      Pearson's Chi-square and logistic regression were used to statistical analysis.
      RESULTS: The mean (SD) age for IBS patients 36.3 (13.5) years and 33.1 (9.9)
      years in non-IBS group (P < 0.001). Frequency of IBS defined by Rome III criteria
      was higher in females and younger individuals. Univariate analysis showed that
      IBS in males was associated with a lower monthly income and educational level and
      in females younger age, single, lower monthly income and educational level, body
      mass index (BMI), and unemployment status. Multivariate logistic regression
      identified a low level of education in males (Odds ratio [OR] = 3.6, 95%
      Confidence interval [CI]: 1.4-9.6) and in females, lower education level (OR =
      2.4, 95% CI: 1.1-5.2), lower BMI (OR = 0.94, 95% CI: 0.89-0.99), unemployed (OR =
      0.31, 95% CI: 0.11-0.85) and smoking (OR = 6.2, 95% CI: 1.03-37.2). CONCLUSION:
      We identified demographic factors in IBS patients. Being single and having a
      lower educational level, income, lower BMI and being unemployed were the most
      important factors associated with IBS, particularly in females.

PMID- 24116321
TI  - Effects of potassium iodide on low avid immunological reactions: probable
      mechanism of action on selective fungal infections.
AB  - BACKGROUND: Selective in-vivo anti-fungal action of potassium iodide (KI) is an
      enigma, but circumstantial evidences strongly indicate some immune mechanism.
      AIM: Study was to demonstrate in-vitro immune-modulating role of KI. MATERIALS
      AND METHODS: In identical test conditions keeping appropriate control, different
      immunological tests were performed with and without 0.1% effective concentration
      of KI. i) Sera from Coombs positive mothers were treated with O, Rh-positive
      erythrocyte suspensions along with Coombs' sera (CS)/Bovine albumin (BA)/KI. ii)
      Amboceptor and complement (C) mixtures were titrated for hemolysis with or
      without KI. iii) Suspension of Salmonella Typhi with positive sera from enteric
      cases and C + KI was incubated at 37 degrees C for 30 minutes, then sub-cultured
      on MacConkey Agar. iv) Positive serum from chronic muco-cutaneous candidiasis
      patient was treated with suspension of candida isolate and C + KI at 37 degrees C
      for 30 minutes then sub-cultured to note variations in colony counts. The data
      was analyzed by Fishers exact test using Graphpad Prism 5 version 5.00
      (California USA). RESULTS: i) KI like BA or CS showed hemagglutination. ii) C
      mediated hemolysis was inhibited in presence of KI. iii) C-mediated lysis of S.
      typhi was partially enhanced by KI showing reduced number of colonies; iv) while
      lysis of candida was reduced. CONCLUSIONS: KI increases avidity of some immune
      reactions including C-mediated cell lysis. An increase or decrease of cell-lysis
      resulted by KI probably mediates by altered access of C-binding receptors. Thus,
      hypothetically, a non-protective Splendore Hoeppli-like deposit around fungus may
      turn into protective immune mechanism by influence of KI.

PMID- 24116322
TI  - Iron deficiency among non-anemic under-five children in enugu, South-East,
      Nigeria.
AB  - BACKGROUND: Iron deficiency has been described as the world most common
      nutritional deficiency and the commonest cause of nutritional anemia in infancy
      and childhood. The deleterious behavioral and cognitive deficit associated with
      iron-deficiency anemia could be irreversible. Therefore, the latter should be
      prevented by early detection of iron deficiency in the non-anemic groups. AIM: To
      determine the prevalence of iron deficiency in the non-anemic under-five children
      and to document its variation among the age classes of these children. SUBJECTS
      AND METHODS: Under-five children presenting at a tertiary hospital were
      consecutively enrolled, Serum ferritin levels of the subjects were used to assess
      the iron status and serum ferrritin level of less than 12 ng/ml was considered as
      iron deficiency. Data were analyzed using SPSS version 15.0. Chi-square tests
      were employed as necessary for test of significance in each of the
      characteristics of the population at P <= 0.05. RESULTS: A total of 178 non
      anemic under-five children were studied, their mean hematocrit and serum
      ferrritin values were 35.5 (2.8%) and 54.9 (76.1) ng/ml respectively. Forty-nine
      (27.5% [49/178]) of the study population was iron deficient and there was no
      significant difference in the prevalence of iron deficiency among the age classes
      (P = 0.75). CONCLUSION: This study has documented a high prevalence of iron
      deficiency in non-anemic under-five children presenting at the outpatient
      department and emergency room of a tertiary health facility in Enugu. All the age
      classes were relatively affected. A further research into the causes of iron
      deficiency in this age group is recommended.

PMID- 24116323
TI  - A study on childhood death at a tertiary care level in ernakulam district.
AB  - BACKGROUND: Childhood mortality is increasing day by day. It will affect the
      development of the nation. Preventive measures on childhood mortality could be an
      effective approach for saving child's life. AIM: To find out the causes of deaths
      among children below 12 years of age those who were admitted in a teaching
      hospital during the period from April 2005 to March 2010. MATERIALS AND METHODS:
      A retrospective study was conducted with hospitalized patients below 12 years
      those who died in a Teaching Hospital from April 1, 2005 to March 31, 2010. The
      data were collected from the registers maintained in the Medical Records
      Department. The data were analysed by using Microsoft Excel. Z test was applied
      for the comparison of proportions. P value less than or equal to 0.05 indicates
      that there is significance difference between the proportions of two groups.
      RESULTS: Child deaths below 12 years of age during the period April 1, 2005 to
      March 31, 2010 were 459. Of these deaths 62.0% (285/459) of all child deaths were
      males and 37.9% (174/459) of all child deaths were females. Most of the deaths
      were in the neonatal period (deaths within 28 days of life). Most of the deaths
      occurred due to certain conditions originating in the perinatal period 52.2%
      (240/459) of all child deaths. Of the deaths occurred due to certain conditions
      originating in the perinatal period, 60% (144/240) of deaths were due to
      respiratory and cardiovascular disorders. CONCLUSION: Neonatal deaths were
      increasing each year. Conduct Health awareness programmes for reducing the
      neonatal deaths. And also improve the antenatal and newborn care for reducing the
      neonatal deaths.

PMID- 24116324
TI  - Stress and Minor Psychiatric Morbidity among Nigerian Executives: Some Socio
      demographic and Biological Correlates.
AB  - BACKGROUND: Stress among "the executives" often arises from the demands of
      leadership and other social responsibilities. AIM: This study aims to determine
      factors associated with stress and minor psychiatric morbidities among Nigerian
      executives. SUBJECTS AND METHODS: A total of 337 management cadre staff attending
      a health workshop, from various private organizations and belonging to different
      professional groups participated in this study. They completed the general health
      questionnaire-12 and a proforma for basic demographic and work data. The data was
      analyzed using SPSS for Windows, version 15 (Chicago IL, USA). The distribution
      of the outcome measure (GHQ Likert Score) was skewed and so data obtained was
      analyzed using non-parametric tests. RESULTS: Certain cardiovascular and
      biochemical assessments were also carried out. Low overall stress level and a
      psychiatric morbidity prevalence of 14.2% (48/337) were found. The female and the
      unmarried executives were more vulnerable to stress. Subject's pulse rate and
      blood cholesterol level appeared to be valuable as stress indicators. CONCLUSION:
      The overall stress level is low, and it is associated with certain biological
      measures (pulse rate and blood cholesterol). The author suggested that the need
      for mental health services in the workplace for the entire workforce.

PMID- 24116325
TI  - Incidence, pattern and management of ovarian cancer at a tertiary medical center
      in enugu, South East Nigeria.
AB  - BACKGROUND: The incidence of ovarian cancer is thought to be increasing in
      developing countries and little is known about the pattern and incidence of this
      disease in South-East Nigeria. AIMS: The objectives of the study were to
      determine the incidence, describe the pattern and management of ovarian cancer at
      a tertiary medical center in Enugu South East Nigeria. MATERIALS AND METHODS:
      This was a retrospective review of cases of histologically diagnosed primary
      ovarian cancer at the study center over 11 years. Cases of histologically
      diagnosed primary ovarian cancer were identified through the records of the study
      center cancer registry and confirmed from the records of the histopathology
      department. Case notes, admission and theatre records were used to obtain data
      relating to clinical management, mortality and incidence of primary ovarian
      cancer. Statistical analysis was dose using SPSS statistical software version
      17.0 for windows. Descriptive and inferential statistics were applied to obtain
      rates, proportions and 95% confidence intervals for these estimates. RESULTS:
      There were 20,227 gynecological admissions during the study period (from January
      2000 to December 2010) and 206 gynecological cancers. There were 54 cases of
      primary ovarian cancer giving an incidence rate of 1/405 gynecological admissions
      per year or 0.3% (95% confidential interval [CI] 0.23%, 0.38%) or 2.4% (54/206)
      per gynecological cancer per year. Epithelial ovarian cancer constituted 68% of
      cases of ovarian cancer (95% CI 54%, 82%): Sex cord and germ cell tumors
      constituted 16% each (95% CI 6%, 26%). Approximately 60% of women who had
      epithelial ovarian cancer were aged 50 years or below (95% CI 47%, 74%) and 72%
      of epithelial ovarian cancer occurred in multiparous women (95% CI 72.1%, 91.9%).
      Over 84% of ovarian cancer presented in stages 3 and 4 of the disease (95% CI
      94%, 72%). The mainstay of management was surgery: Compliance with cis-platinum
      based adjuvant chemotherapy was poor. Case-specific mortality rate within 1 year
      of diagnosis was, at least, 70% (95% CI 64%, 84%). CONCLUSIONS: Primary ovarian
      cancer was uncommon and consisted mainly of epithelial cancer. Epithelial ovarian
      cancer occurred more in multiparous women and in women under 50 years in our
      center contrary to the known pattern of the disease.

PMID- 24116326
TI  - Nutrition intervention program and childhood malnutrition: a comparative study of
      two rural riverine communities in bayelsa state, Nigeria.
AB  - BACKGROUND: The prevalence of malnutrition is high in the Niger delta region of
      Nigeria, in spite of the region's oil wealth and nutrition intervention programs
      have been found to be effective in similar circumstance. AIM: This study is to
      assess the nutrition intervention program, implemented by UNICEF in some rural
      communities of Bayelsa State, one of the six States in the Niger delta region of
      Nigeria. SUBJECTS AND METHODS: The study was carried out in 2009 in Toruorua and
      Gbaranbiri, two rural riverine communities, in Baylesa State. Toruorua benefited
      from the nutrition intervention program of UNICEF between 1999 and 2008, while
      Gbaranbiri did not benefit. A comparative, cross-sectional study design was used,
      with the data collected using anthropometry and semi-structured questionnaire,
      administered on 105 respondents, chosen with the cluster sampling technique,
      popularized by UNICEF, from each of the study communities. Data were analyzed
      using EPI-INFO version 2002, Microsoft Excel software, and manually. Differences
      between the study communities were tested using the student's t-test for means,
      and Chi-square test for proportions. Significant values were set at P <0.05.
      RESULTS: A total of 210 questionnaires were administered and retrieved from both
      study communities, and the anthropometric measurements of equal number of under
      five year children were also taken. There were no significant differences in the
      occupations of the respondents, and in the sizes of their households. The
      prevalence of wasting, under-weight and stunting were however found to be
      significantly higher in the reference community, as 20.0% (21/105) of the
      children were found to be wasted, compared to 5.0% (6/105) in the intervention
      community (P < 0.01); 17.1% (18/105) were found to be underweight, compared to
      9.5% (10/105) in the exposed community (P = 0.01); while 24.8% (26/105) were
      stunted, compared to 10.5% (11/105) in the exposed community (P = 0.01).
      CONCLUSION: Nutrition intervention program delivered in a primary health care
      facility can positively change nutrition behavior and prevent childhood
      malnutrition.

PMID- 24116327
TI  - Compliance with seat belt use in makurdi, Nigeria: an observational study.
AB  - BACKGROUND: Seat belts are designed to reduce injuries due to road crash among
      vehicle occupants. AIMS: This study aims to determine the availability of seat
      belt in vehicles and compliance with seat belt use among vehicle occupants.
      MATERIALS AND METHODS: This was a 24-h direct observational study of seat belt
      usage among vehicle occupants in Makurdi, Benue State, Nigeria. By direct
      surveillance and using a datasheet, we observed 500 vehicles and their occupants
      for seat belt availability and compliance with its use. Chi-square test was used
      for test of significance between variables. RESULTS: Twenty-five (5.0%) of the
      observed 500 vehicles had no seat belt at all. Overall, compliance was 277/486
      (57.0%). Use of seat belt was highest in the afternoon with 124/194 (64.4%),
      followed by 111/188 (59.0%) in the morning and 42/95 (44.2%) at night. Compliance
      was highest among car occupants [209/308 (67.9%)] and private vehicles, and
      lowest among commercial vehicle occupants. Compliance among female drivers was
      77.1% compared with 51.4% among male drivers. Among drivers, the mean age of seat
      belt users was 38.4 (7.7) years, which was significantly younger than the 41.3
      (8.7) years mean age of non-users. Similar figures were obtained among other
      vehicle occupants. CONCLUSIONS: Compared with previous studies, seat belt usage
      has improved among Nigerian road users, but there is still room for improvement,
      especially early in the mornings and at nights. Since these were times when law
      enforcement agencies were not likely to be on the roads, we advocate for improved
      coverage by enforcement agents to enforce better compliance.

PMID- 24116328
TI  - Effect of non-surgical periodontal therapy on the concentration of volatile
      sulfur compound in mouth air of a group of nigerian young adults.
AB  - BACKGROUND: The major goal of non-surgical periodontal therapy is to reduce or
      eliminate the subgingival pathogenic microbial flora that is known to be
      associated with volatile sulfur compounds (VSC). AIM: The aim of this study was,
      therefore, to determine the effect of non-surgical periodontal therapy on the
      concentration of VSC in mouth air of young adults. SUBJECTS AND METHODS: Four
      hundred subjects, grouped into two based on the absence or presence of
      periodontal diseases, were involved in this study. Basic periodontal examination
      was used for the grouping. The measurement of the concentration of the VSC in the
      mouth air of the subjects was done objectively, using the Halimeter, before and
      after the therapy, and at recall visits 2 weeks and 6 weeks after therapy. Chi
      square and Paired t-test were used to find statistical significance. RESULTS: The
      results revealed that at baseline, 78.7% (48/61) of the subjects who had VSC
      concentration more than 250 parts per billion (ppb) were from the group with
      periodontal disease. Immediately after non-surgical periodontal therapy, only
      8.5% (17/200) of the subjects with periodontal disease had VSC concentration of
      more than 250 ppb while all the subjects with no periodontal disease had VSC
      concentration less than 181 ppb. The same pattern of reduction in the
      concentration of the VSC and improvement in oral hygiene was also obtained 2
      weeks and 6 weeks after therapy. CONCLUSION: It can be concluded that non
      surgical periodontal therapy brought about reduction in the concentration of
      volatile sulfur compounds in mouth air of young adults.

PMID- 24116329
TI  - Prescription pattern in the department of surgery in a tribal district hospital
      of andhra pradesh, India.
AB  - BACKGROUND: Usually, surgical management cannot be completed without the use of
      antimicrobial and analgesic drugs. Irrational prescription may lead to severe
      postoperative complications. AIM: The objective of this study was to evaluate the
      prescription trend in the surgery department of a tribal district hospital so as
      to determine the extent of rational use of medicines. MATERIALS AND METHODS: It
      was a retrospective study in which 50 cases were selected randomly. Case records
      were analyzed for prescription trend. Data was analyzed using Microsoft Office
      Excel 2007 and values were presented descriptively. RESULTS: Most of the cases
      were between the age group of 21 and 40 years, 18 cases (36%). Commonest cause of
      hospitalization was renal calculi (10 (20%)) followed by acute abdomen and
      abscess (6, (12%)). Total of 255 numbers of drugs were used with an average of
      5.1 drugs per patient. Most preferred route was intravenous route (174 drugs,
      68.2%). Antimicrobial was the most common (97 (38.0%)) group of drugs followed by
      analgesic/antipyretics (50 (19.6%)). Among antimicrobials, ciprofloxacin (22
      (22.7%)) was the most common drug followed by metronidazole (21 (18.5%)). All the
      cases were managed by empirical treatment. Two different antimicrobials were
      prescribed to 20 (40%) of cases. Dosage of 83 (32.6%) drugs was inappropriate
      while frequency was inappropriate in 26 (10.2%) cases. CONCLUSION: Urgent steps
      like specific guidelines, training, and monitoring of drugs use are needed to
      correct some irrational approaches.

PMID- 24116330
TI  - A comparative study of effects of omega-3 Fatty acids, alpha lipoic Acid and
      vitamin e in type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetes Mellitus is a metabolic disorder characterized by abnormal
      lipid and glucose metabolism. Various modes of adjuvant therapy have been
      advocated to ameliorate insulin resistance. AIM: This study was intended to
      assess the effects of antioxidants; alpha lipoic acid (ALA), omega 3 fatty acid
      and vitamin E on parameters of insulin sensitivity (blood glucose and HbA1c) in
      patients of type 2 diabetes mellitus with documented insulin resistance. SUBJECTS
      AND METHODS: It was a prospective, randomized, double blind, placebo controlled,
      single centered study. 104 patients with type 2 diabetes mellitus with insulin
      resistance were recruited. They were given ALA, omega 3 fatty acid, vitamin E or
      placebo. Fasting blood glucose and HbA1c were measured at first visit (V1) and
      after 90 days (V2). Statistical analysis was carried out by paired t-test by
      using SPSS software version 11 (SPSS, Chicago, USA). RESULTS: Analysis of
      baseline (V1) vs. end of treatment period (V2) parameters, showed significant
      decrease in HbA1c in the three treatment group. We also observed decrease in
      fasting blood glucose in the three treatment group but it was not statistically
      significant (Gr. I = 0.51, Gr. II = 0.05, Gr. III = 0.22, Gr. IV = 0.88).
      CONCLUSION: ALA, Omega 3 fatty acid and vitamin E can be used as add on therapy
      in patients with type 2 diabetes mellitus to improve insulin sensitivity and
      lipid metabolism.

PMID- 24116331
TI  - Treatment outcomes of auricular hematoma using corrugated rubber drains: a pilot
      study.
AB  - BACKGROUND: Hematoma of the auricle which is a collection of blood beneath the
      perichondrial layer of the pinna usually poses a challenge to the
      otolaryngologist due to its high rate of recurrence after treatment and lack of
      appropriate material for use as stitch dressing especially, in the developing
      world. This is a Pilot study in which corrugated rubber drain was used as a
      stitch dressing after routine incision and drainage (I and D) in patients who
      presented with auricular hematoma. AIM: To determine the effectiveness of
      corrugated rubber drain in the treatment of auricular hematoma. SUBJECTS AND
      METHODS: A total of seven patients were seen within a 2 year period in an ENT
      Ear, nose and throat clinic. Two patients had simple I and D done, one patient
      had suturing of the auricle between improvised plastic material used for stitch
      dressing after I and D, while four patients had I and D done and subsequently, a
      corrugated rubber drain was used as the stitch dressing. RESULTS: Two patients
      treated with simple I and D had recurrence of hematoma, the patient treated with
      improvised plastic material had pressure necrosis of areas of the pinna which
      however improved when dressing was removed as soon as symptoms were noticed 2
      days post-operatively. Four patients who had I and D and subsequent use of rubber
      drain as stitch dressing, had un-eventful recoveries. CONCLUSION: Corrugated
      rubber tubing drains which are readily available in a developing country like
      ours has been found very useful as stitch dressing in the management of auricular
      hematoma.

PMID- 24116332
TI  - Bilateral additional slips of triceps brachii forming osseo-musculo-fibrous
      tunnels for ulnar nerves.
AB  - Rare additional slips of triceps brachii muscle was found bilaterally in a sixty
      two year old South Indian male cadaver during routine dissection of upper limb
      for undergraduate students at Melaka-Manipal Medical College, Manipal University,
      Manipal, India. On left side, the variant additional muscle slip took origin from
      the lower part of the medial intermuscular septum about 4 cm proximal to the
      medial humeral epicondyle. From its origin, the muscle fibres were passing over
      the ulnar nerve and were joining the triceps muscle to get inserted to the upper
      surface of olecranon process of ulna. On right side, the additional muscle slip
      was larger and bulkier and was arising from the lower part of the medial border
      of the humerus about 4 cm proximal to the medial epicondyle in addition to its
      attachment to the medial intermuscular septum. On both sides, the additional
      slips were supplied by twigs from the radial nerve. On both sides, the ulnar
      nerve was passing between variant additional slip and the lower part of the shaft
      of the humerus in an osseo-musculo-fibrous tunnel. Such variant additional muscle
      slips may affect the function of triceps muscle and can lead to snapping of
      medial head of triceps and ulnar nerve over medial epicondyle and also can
      dynamically compress the ulnar nerve during the contraction of triceps leading to
      ulnar neuropathy around the elbow. 

PMID- 24116333
TI  - Acute dystonic reaction as medical emergency: a report of two cases.
AB  - Drug-induced dystonic reactions are common presentations to the emergency
      department. Two cases of acute dystonic reactions presenting as acute medical
      emergency illustrate the associated fatality and possibility of misdiagnosis.
      This case series reports two cases of medication-induced (haloperidol and
      metoclopramide) acute dystonic reactions presenting with torticollis, tongue
      protrusion, and respiratory distress which resolved with the administration of
      intramuscular biperiden and oxygen by facemask. In developing countries like
      Nigeria where atypical anti-psychotic medications with fewer and lesser
      troublesome side effects are not affordable to many, the training of physicians
      and other doctors should adequately include a high degree of clinical suspicion
      and knowledge of management of acute dystonic reactions. 

PMID- 24116334
TI  - Large vesico-vaginal fistula caused by a foreign body.
AB  - Foreign body is a rare cause of vesico-vaginal fistula most often reported in
      developed countries. In developing countries obstructed labor is the commonest
      cause of fistula. A nulliparous 19-year-old female presented with a 3-week
      history of a foreign body in the vagina causing urinary incontinence and
      offensive vaginal discharge. Her guardian allegedly inserted the foreign body
      after she refused a pre-arranged marriage. A plastic container was removed from
      the vagina under general anesthesia. A large vesico-vaginal fistula was
      discovered, which was successfully surgically repaired. We recommend urgent
      removal of the foreign body, preferably under general anesthesia. However, if the
      history or physical examination reveals prolonged exposure, repair of the fistula
      should be delayed to allow for adequate debridement in order to prevent any life
      threatening complications. 

PMID- 24116335
TI  - Recurrent Perianal Sinus in Young Girl Due To Pre-sacral Epidermoid Cyst.
AB  - Pre-sacral epidermoid cysts are rare development cysts resulting from
      dysembryogenesis mostly diagnosed in middle aged women. We report a case of pre
      sacral epidermoid cyst presenting with recurrent perianal sinus in young girl.
      Generally pre-sacral epidermoid cysts are seen in adult age group but it is rare
      presentation in young age group. We report a rare case of presacral epidermoid
      cyst occurring in a young female. 

PMID- 24116336
TI  - Fever of unknown origin: a case of post obstructive pneumonia complicating mature
      teratoma.
AB  - Mediastinal teratomas are rare germ cell tumors in children accounting for only
      4.3% of all germ cell tumours. Here, we describe a three year old child who was
      misdiagnosed as a case of pulmonary tuberculosis at periphery despite of his
      chest X ray showing large homogenous opacification of left hemithorax with areas
      of calcifications and subsequently diagnosed as a case of benign mature teratoma
      with post obstructive pneumonia. Our case highlights the need for careful
      evaluation of chest X-ray (CXR) by the treating physicians, especially when CXR
      had a large homogenous opacity with shifting of mediastinum and presence of a few
      calcified shadows, which may clinch a rare diagnosis of an uncommon disorder. 

PMID- 24116337
TI  - Impacted laryngeal foreign body in a child: a diagnostic and therapeutic
      challenge.
AB  - Impacted laryngeal foreign body could lead to catastrophic consequences if
      appropriate diagnostic and therapeutic procedures are not promptly instituted. A
      case of 4-year-old child who presented with a 4-day history of probable ingestion
      or aspiration of a pen part and history of occasional noisy breathing on exertion
      and swallowing is reported. On examination, the child appeared asymptomatic on
      general examination. CT scan of larynx and chest revealed foreign body in the
      larynx. A conical plastic foreign body in the laryngotracheal junction was
      retrieved by rigid bronchoscopy. The asymptomatic nature of the foreign body was
      related to the presence of a lumen within the foreign body permitting ventilation
      and the inert nature of the material. The case demonstrates the importance of the
      history, CT scan in case of suspicion, and the need for urgent bronchoscopy with
      appropriate anesthetic technique. 

PMID- 24116338
TI  - Oral Health in Pregnancy: Old problem, New Findings Yet More Predicaments.

PMID- 24116339
TI  - Disaster management: fallacies and solutions: an Indian perspective.

PMID- 24116340
TI  - Stuttering among children exposed to (family) high expressed emotion families.

PMID- 24116342
TI  - Does pramipexole treatment improve headache in patients with concomitant migraine
      and restless legs syndrome?
AB  - BACKGROUND: Recent studies have suggested a strong link between migraines and
      restless legs syndrome (RLS). It is possible that these disorders share a
      dopaminergic dysfunction in the hypothalamic A11 nucleus that contributes to this
      association. However, there have been no clinical studies to evaluate the effect
      of dopaminergic treatment on migraine symptoms in patients with concomitant
      migraines and RLS. METHODS: We present an illustrative patient with concomitant
      RLS and migraine who showed improvement in her headache frequency and RLS
      symptoms following immediate-release pramipexole (P-IR) treatment and provide
      review results from the medical records of patients who experienced both
      migraines and RLS in our previous cross-sectional study. RESULTS: Ten patients
      (nine patients from the previously completed single-center study) received P-IR
      treatment were included in the study. RLS symptoms improved markedly in all of
      the subjects. Five out of the 10 patients (50%) reported improvement in migraine
      headaches. Of these five patients, four (80%) had reported morning headaches
      before P-IR treatment. DISCUSSION: Our results indicate that the identification
      of RLS in migraine patients is clinically significant and that dopaminergic
      treatment may improve both migraines, particularly morning headache (80%
      improvement in this study), and RLS symptoms. However, further clinical studies
      are warranted to verify our results.

PMID- 24116343
TI  - Slowed saccades and increased square wave jerks in essential tremor.
AB  - BACKGROUND: Eye movements in essential tremor (ET) are poorly described and may
      present useful information on the underlying pathophysiology of the disorder.
      METHODS: Sixty patients with ET, including 15 de novo untreated patients, and 60
      age-matched controls constitute the study population. A video-based eye tracker
      was used to assess binocular eye position. Oculomotor function was assessed while
      subjects followed random horizontally and vertically step-displaced targets.
      RESULTS: For all reflexive saccades, latencies were increased in ET subjects by a
      mean of 16.3% (p<0.01). Saccades showed reduced peak velocities with a lengthy,
      wavering velocity plateau, followed by slowed decelerations. For larger 30
      degrees + saccades, peak velocities were decreased by a mean of 25.2% (p<0.01)
      and durations increased by 31.8% (p<0.01). The frequency of square wave jerks
      (SWJs) in patients was more than triple that of controls (p<0.0001). Despite
      frequent interruptions by SWJs, fixations were otherwise stable and
      indistinguishable from controls (root mean square [RMS] velocity, p = 0.324). The
      abnormal eye movement parameters were independent of disease duration, tremor
      severity, and medication therapy. DISCUSSION: In contrast to normally swift onset
      and efficient acceleration/deceleration movements, saccades in ET are
      characterized by abnormally prolonged latencies and slowed velocity profiles.
      Although ET subjects maintain highly stable fixations, they are interrupted by
      increased numbers of SWJs. This study reveals novel oculomotor deficits in ET,
      which are distinct from the eye movement dysfunction of other movement disorders,
      supporting a role for eye tracking to assist in the differential diagnoses of not
      only atypical, but also more common movement disorders.

PMID- 24116344
TI  - Prevalence of Essential Tremor on Arosa Island, Spain: a Community-based, Door-to
      Door Survey.
AB  - BACKGROUND: The prevalence of essential tremor (ET) is still not well understood
      and the various studies performed to date have generated highly variable results.
      Few epidemiologic studies on the prevalence of ET have been reported from Spain.
      METHODS: A one-stage door-to-door survey was conducted on Arosa Island,
      northwestern Spain, to determine the prevalence of ET in the population aged 65
      years and older. The diagnostic criteria for ET were the presence of non-dystonic
      head tremor or moderate- to severe-amplitude tremor on at least four tests of the
      revised Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET)
      Scale. RESULTS: A total of 65 individuals with ET (28 males, 37 females) were
      identified, resulting in a crude prevalence of 8.63% (adjusted rate 8.42%).
      Prevalence increased with advancing age. There were no significant differences in
      prevalence between sexes in any of the age groups. Among the prevalent cases,
      12.3% (n = 8) had been previously diagnosed. Only 29.2% (n = 19) reported
      functional disability caused by tremor. A family history of tremor was reported
      in 35.4% (n = 23). DISCUSSION: The prevalence of ET was higher than that seen in
      similar populations in Spain and other countries. A high proportion of those with
      ET were previously undiagnosed. Since Arosa Island has been a relatively isolated
      area, these results might indicate a predominant role, at least in the elderly,
      for genetic factors in the development of ET.

PMID- 24116345
TI  - Tremor in Multiple System Atrophy - a review.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative movement
      disorder characterized by a rapidly progressive course. The clinical presentation
      can include autonomic failure, parkinsonism, and cerebellar signs.
      Differentiation from Parkinson's disease (PD) is difficult if there is levodopa
      responsive parkinsonism, rest tremor, lack of cerebellar ataxia, or mild/delayed
      autonomic failure. Little is known about tremor prevalence and features in MSA.
      METHODS: We performed a PubMed search to collect the literature on tremor in MSA
      and considered reports published between 1900 and 2013. RESULTS: Tremor is a
      common feature among MSA patients. Up to 80% of MSA patients show tremor, and
      patients with the parkinsonian variant of MSA are more commonly affected.
      Postural tremor has been documented in about half of the MSA population and is
      frequently referred to as jerky postural tremor with evidence of
      minipolymyoclonus on neurophysiological examination. Resting tremor has been
      reported in about one-third of patients but, in contrast to PD, only 10% show
      typical parkinsonian "pill-rolling" rest tremor. Some patients exhibit intention
      tremor associated with cerebellar dysmetria. In general, MSA patients can have
      more than one tremor type owing to a complex neuropathology that includes both
      the basal ganglia and pontocerebellar circuits. DISCUSSION: Tremor is not rare in
      MSA and might be underrecognized. Rest, postural, action and intention tremor can
      all be present, with jerky tremulous movements of the outstretched hands being
      the most characteristic. However, reviewing the data on tremor in MSA suggests
      that not every shaky movement satisfies tremor criteria; therefore, further
      studies are needed.

PMID- 24116341
TI  - TEC and MAPK Kinase Signalling Pathways in T helper (TH) cell Development, TH2
      Differentiation and Allergic Asthma.
AB  - Significant advances in our understanding of the signalling events during T cell
      development and differentiation have been made in the past few decades. It is
      clear that ligation of the T cell receptor (TCR) triggers a series of proximal
      signalling cascades regulated by an array of protein kinases. These orchestrated
      and highly regulated series of events, with differential requirements of
      particular kinases, highlight the disparities between alphabeta+CD4+ T cells.
      Throughout this review we summarise both new and old studies, highlighting the
      role of Tec and MAPK in T cell development and differentiation with particular
      focus on T helper 2 (TH2) cells. Finally, as the allergy epidemic continues, we
      feature the role played by TH2 cells in the development of allergy and provide a
      brief update on promising kinase inhibitors that have been tested in vitro, in
      pre-clinical disease models in vivo and into clinical studies.

PMID- 24116346
TI  - (18)F-FDG imaging of human atherosclerotic carotid plaques reflects gene
      expression of the key hypoxia marker HIF-1alpha.
AB  - To investigate the association between gene expression of key molecular markers
      of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2
      [(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron
      emission tomography (PET). Studies using PET have demonstrated (18)F-FDG-uptake
      in patients with confirmed plaques of the carotid artery. Inflammatory active or
      "vulnerable" plaques progressively increase in bulk, develop necrotic cores, poor
      vessel-wall vascularization and become prone to hypoxia. We used quantitative
      polymerase-chain reaction (qPCR) to determine gene expression of hypoxia
      inducible factor 1alpha (HIF-1alpha) and cluster of differentiation 68 (CD68) on
      plaques recovered by carotid endarterectomy (CEA) in 18 patients. Gene expression
      was compared with (18)F-FDG-uptake quantified as the maximum standardized uptake
      value (SUVmax) on co-registered PET/computed tomography (CT) scans performed the
      day before CEA. Immunohistochemistry was used to validate target-gene protein
      expression. In univariate linear regression analysis HIF-1alpha was significantly
      correlated with (18)F-FDG-uptake (SUVmax) as was CD68. A two-tailed Pearson
      regression model demonstrated that HIF-1alpha and CD68 gene expression co
      variated and accordingly when entering the variables into multivariate linear
      regression models with SUV-values as dependent variables, HIF-1alpha was
      eliminated in the final models. (18)F-FDG-uptake (SUVmax) is correlated with HIF
      1alpha gene expression indicating an association between hypoxia and glucose
      metabolism in vivo. The marker of inflammation CD68 is also associated with (18)F
      FDG-uptake (SUVmax). As CD68 and HIF-1alpha gene expression co-variate their
      information is overlapping. 

PMID- 24116347
TI  - PET/MR imaging of atherosclerosis: initial experience and outlook.
AB  - Hybrid scanners such as PET/CT have in the past emerged as a valuable modality in
      clinical routine as well as an important research tool. Recently, the newly
      developed fully integrated PET/MR scanners were introduced to the market, raising
      high expectations especially due to the excellent soft tissue contrast and
      functional imaging capabilities of MRI. In this issue of the American Journal of
      Nuclear Medicine and Molecular Imaging, initial experiences using a hybrid PET/MR
      scanner for carotid artery imaging in a group of patients with increased risk for
      atherosclerosis are described. This represents a proof-of-principle study, which
      could stimulate future applications of this powerful modality in atherosclerotic
      plaque imaging. 

PMID- 24116348
TI  - A comparison of PET imaging agents for the assessment of therapy efficacy in a
      rodent model of glioma.
AB  - The aim of the current study was to assess the ability of PET imaging agents to
      detect early response to therapy in an orthotopic experimental rodent model of
      glioma. Clinically, MRI and [(18)F]FDG PET are routinely used but their ability
      to assess early therapeutic response can be limited. In this study, nude rats
      were implanted with U87-MG tumors orthotopically and imaged with either
      [(18)F]FDG or [(18)F]FLT to determine which tracer acts as the most sensitive
      biomarker for evaluation of treatment response in animals undergoing anti
      angiogenic therapy with sunitinib, a receptor tyrosine kinase (RTK) inhibitor. Of
      the radiopharmaceuticals tested, [(18)F]FLT proved to be the most sensitive
      biomarker in the proliferating glioma, based on tumour-to-normal tissue
      radiotracer uptake (TNR ~17) in comparison to [(18)F]FDG (TNR ~1.7). Furthermore,
      [(18)F]FLT displayed earlier assessment of therapy efficacy, than either tumour
      volume measured by MRI or [(18)F]FDG PET imaging. Overall, longitudinal molecular
      imaging with [(18)F]FLT provides earlier detection of therapy response than
      either of the commonly used clinical imaging modalities potentially improving
      patient management. 

PMID- 24116349
TI  - PET/CT vs. non-contrast CT alone for surveillance 1-year post lobectomy for stage
      I non-small-cell lung cancer.
AB  - (18)F-FDG PET/CT was compared with non-contrast chest CT in monitoring for
      recurrence 1-year after lobectomy of stage 1 non-small-cell lung cancer (NSCLC).
      For surveillance after treatment with curative intent, current (April 2012)
      National Comprehensive Cancer network guidelines recommend chest CT with or
      without contrast every 6-12 months for 2 years, then non-contrast chest CT
      annually. PET/CT is not currently indicated for routine follow-up. One hundred
      patients receiving surveillance PET/CT 1-year after lobectomy for the treatment
      of stage 1a or 1b NSCLC were included in the study. Exclusion criteria included
      the presence or interval diagnosis of a second malignancy, or surgical treatment
      more radical than single lobectomy. The non-contrast CT obtained from the 1-year
      PET/CT was interpreted by an experienced chest radiologist blinded to the PET/CT
      for evidence of recurrence using the following findings: pulmonary nodule,
      pleural effusion, pleural mass, adenopathy, and extrathoracic mass. The ecision
      about recurrence was made solely from the non-contrast CT without PET/CT
      findings. This was compared with the determination made with PET/CT. The
      reference standard for determination of recurrence was the multi-disciplinary
      tumor board who had access to all imaging and clinical data. Recurrence at 1 year
      was documented in 16 of 90 patients. All 16 recurrences were documented with
      PET/CT and 9 were found with non-contrast CT. Five of the 7 recurrences missed
      with non-contrast CT were extrathoracic metastases. Sensitivity of CT and PET/CT
      for recurrence was 56.3% and 100%, respectively (p = 0.015). Specificity of CT
      and PET/CT for recurrence was 95.9% and 93.2%, respectively (p = 0.62). 

PMID- 24116350
TI  - Dynamic PET with (18)F-Deoxyglucose (FDG) and quantitative assessment with a two
      tissue compartment model reflect the activity of glucose transporters and
      hexokinases in patients with colorectal tumors.
AB  - Dynamic PET (dPET) with (18)F-Deoxyglucose (FDG) provides quantitative
      information about distribution of the tracer in a predefined volume over time. A
      two-tissue compartment model can be used to obtain quantitative data regarding
      transport of FDG into and out of the cells, phosphorylation and dephosphorylation
      rate of intracellular FDG, and fractional blood volume in the target volume, also
      named vessel density. Aim of the study was the correlation of glucose
      transporters expression and hexokinases with the corresponding compartment
      parameters.Patients with colorectal tumors were examined with dynamic PET prior
      to surgery. Afterwards, tumor samples were obtained during surgery and gene
      expression was assessed using gene arrays. The dynamic PET data were evaluated to
      quantify the parameters of a two tissue compartment model for colorectal tumors
      using a Volume-of-Interest (VOI) technique. A multiple correlation/regression
      analysis was performed using glucose transporters as independent variables and k1
      as the dependent variable. A correlation of r=0.7503 (p=0.03) was obtained for
      the transporters SLC2A1, SLC2A2, SLC2A4, SLC2A8, SLC2A9, SLC2A10 and k1. The
      correlation of r=0.7503 refers to an explained variance of data of 56.30 %,
      therefore more than 50 % of data changes are associated with the gene expression.
      An analysis of the hexokinases HK1-HK3 and k3 revealed a correlation coefficient
      of r=0.6093 (p=0.04), which is associated with an explained variance of 37.12 %.
      Therefore, parameters k1 and k3 reflect gene activity. The results demonstrate
      that k1 and k3 of the two-tissue compartment model are correlated with glucose
      transporters and hexokinases. 

PMID- 24116351
TI  - Synthesis and in vivo evaluation of an (18)F-labeled glycoconjugate of PD156707
      for imaging ETA receptor expression in thyroid carcinoma by positron emission
      tomography.
AB  - Disturbances of the endothelin axis have been described in tumor angiogenesis and
      in highly vascularized tumors, such as thyroid carcinoma. Consequently, the
      endothelin (ET) receptor offers a molecular target for the visualization of the
      endothelin system in vivo by positron emission tomography (PET). We therefore
      endeavoured to develop a subtype-selective ETA receptor (ETAR) radioligand by
      introduction of a glycosyl moiety as a hydrophilic building block into the lead
      compound PD156707. Employing click chemistry we synthesized the triazolyl
      conjugated fluoroglucosyl derivative 1 that had high selectivity for ETAR (4.5
      nM) over ETBR (1.2 MUM). The radiosynthesis of the glycoconjugate [(18)F]1 was
      achieved by concomitant (18)F-labeling and glycosylation, providing [(18)F]1 in
      high radiochemical yields (20-25%, not corrected for decay, 70 min) and a
      specific activity of 41-138 GBq/MUmol. Binding properties of [(18)F]1 were
      evaluated in vitro, and its biodistribution was measured in K1 thyroid carcinoma
      xenograft nude mice ex vivo and by molecular imaging. Although the very
      substantial excretion via hepatobiliary clearance was not decisively influenced
      by glycosylation, the (18)F-glycoconjugate was more stable in blood during PET
      recordings than was the previously described (18)F-fluoroethoxy analog. Small
      animal PET imaging showed displacable binding of [(18)F]1 at ETAR in K1 tumors.
      The simple and efficient (18)F-radiosynthesis together with the excellent
      stability make the (18)F-labeled glycoconjugate [(18)F]1 a promising molecular
      tool for preclinical PET imaging studies of ETAR expression in thyroid carcinoma
      and other conditions with marked angiogenesis. 

PMID- 24116352
TI  - Bone metastases in GEP-NET: response and long-term outcome after PRRT from a
      follow-up analysis.
AB  - Bone metastases of gastroenteropancreatic neuroendocrine tumors (GEP NET) can be
      associated with pain and a poor prognosis. Peptide receptor radionuclide therapy
      (PRRT) has been shown to be effective against this tumor manifestation. This
      study represents an update of the therapeutic assessment of PRRT with (177)Lu
      octreotate in GEP NET patients with bone metastases focusing on potential
      predictors for impaired outcome and overall survival.We retrospectively analyzed
      a consecutive subgroup of n=68 patients with bone metastases (BM) of GEP NET
      treated with (177)Lu-octreotate (4 intended cycles at 3 monthly intervals; mean
      activity per cycle, 8.1 GBq). Baseline characteristics, including age,
      performance status, tumor origin, tumor load, plasma chromogranin A (CgA), and
      neuron-specific enolase (NSE) were analyzed regarding the impact on tumor
      regression (modified M.D. Anderson criteria) and survival of the patients.
      Survival analyses were performed using Kaplan-Meier curves, log-rank test at a
      significance level of p <0.05, and Cox proportional hazards model for uni- and
      multivariate analyses. Median follow-up was 48 months. The observed response of
      BMs consisted of complete remission in 2 (2.9%), partial remission in 23 (33.8%),
      minor response in 8 (11.8%), stable disease in 26 (38.2%), and progressive
      disease in 8 (13.2%) patients. Median time-to-progression (TTP) of BMs and
      overall survival (OS) were 35 mo (95% CI: 25-45) and 51 mo (95% CI: 38-64),
      respectively. Patients with responding BMs survived significantly longer than
      other patients (median 56 mo vs. 39 mo, p=0.034). NSE >15 ng/ml (p=0.002) and
      Ki67 index >10% (p=0.008) were associated with shorter overall survival. BM of
      GEP NET are effectively controlled by PRRT with a long median progression-free
      survival of approx. 3 years. Non-regression of BM, high proliferation rate and
      increased plasma NSE at baseline are predictive of shorter survival. However,
      this study confirms that poor patient condition (Karnofsky-Index <=70%) and
      multifocality of BM (>10 lesions) do not affect outcome efficacy, further
      encouraging the use of PRRT in advanced bone metastatic disease. 

PMID- 24116353
TI  - Molecular MRI of atherosclerotic plaque progression in an ApoE(-/-) mouse model
      with a CLT1 peptide targeted macrocyclic Gd(III) chelate.
AB  - Molecular imaging of atherosclerotic biomarkers is critical for non-invasive
      detection and diagnosis of atherosclerotic plaques and therapeutic management.
      Fibrin and fibronectin accumulate at elevated levels in atherosclerotic plaques
      and are associated with atherogenesis and disease progression. Molecular imaging
      of these biomarkers has the potential to non-invasively characterize plaque
      burden. In this work, we investigated the effectiveness of a peptide-targeted
      macrocyclic Gd(III) chelate, CLT1-dL-(DOTA-Gd)4, specific to fibrin-fibronectin
      complexes for molecular MRI of atherosclerosis. Atherosclerotic plaques were
      induced in Apolipoprotein E-knockout (ApoE(-/-)) mice by feeding with high fat
      and cholesterol-enriched diet (HFD) for up to 30 weeks. MRI of the vessel wall in
      the arch aorta was performed at 10, 20 and 30 weeks after the onset of HFD. High
      spatial-resolution MRI was performed prior and up to 35 minutes after i.v.
      injection of CLT1-dL-(DOTA-Gd)4 or a nonspecific control agent at a dose of 0.1
      mmol-Gd/kg. CLT1-dL-(DOTA-Gd)4 produced stronger enhancement in the
      atherosclerotic lesions of the aortic wall than the control at all time points in
      the mice. Cross sectional MR images of the aortic arch revealed progressive
      thickening of the atherosclerotic vessel wall in the mice on HFD for up to 30
      weeks. This progression correlated well to histological staining, as well as
      fibrin and fibronectin immunochemical stained images. Molecular MRI with CLT1-dL
      (DOTA-Gd)4 has a potential for detecting atherosclerosis and non-invasive
      monitoring of the progression of the plaques. 

PMID- 24116355
TI  - What would I do if it were my problem?

PMID- 24116356
TI  - Histomorphometric comparison of different concentrations of recombinant human
      bone morphogenetic protein with allogeneic bone compared to the use of 100%
      mineralized cancellous bone allograft in maxillary sinus grafting.
AB  - The purpose of this study was to histomorphometrically evaluate the percentage of
      vital bone after grafting of maxillary sinuses using two different concentrations
      of recombinant human bone morphogenetic protein/acellular collagen sponge (rhBMP
      2/ACS) combined with mineralized cancellous bone allograft (MCBA) and to compare
      the results to a control sinus grafted with MCBA only. Thirty-six sinuses in 18
      patients had two of three of the graft combinations including: (1) control, MCBA
      only; (2) test one, MCBA + 5.6 mL of rhBMP-2/ACS (containing 8.4 mg of rhBMP-2);
      or (3) test two, MCBA + 2.8 mL of rhBMP-2/ACS (containing 4.2 mg of rhBMP-2).
      Histologic cores were taken 6 to 9 month following sinus augmentation. The
      results showed no statistically significant differences in vital bone between the
      two test groups compared to the control sinus group treated with MCBA alone.
      Future studies involving more cases and evaluating survival of implants placed in
      these augmented sinuses are needed to verify the results of this randomized
      prospective study. 

PMID- 24116357
TI  - Influence of implant position on clinical crown length and peri-implant soft
      tissue dimensions at implant-supported single crowns replacing maxillary central
      incisors.
AB  - The aims of this study were to evaluate the influence of implant position on
      clinical crown length and marginal soft tissue dimensions at implant-supported
      single crowns of maxillary central incisors and to validate the papilla index
      score (PIS). Twenty-five patients were included. Standardized and clinical
      photographs and periapical radiographs from baseline were used to assess three
      dimensional positional parameters. The contralateral central incisors were used
      as controls. Paired sample t test and Pearson correlation analysis were used to
      analyze implant position, dimension of crown, and papilla fill. Cohen kappa and
      Spearman correlation were used to validate the PIS. The implant-supported crown
      was statistically significantly longer than the contralateral tooth, and there
      was significant correlation between the orofacial position of the implant and the
      crown length difference. The distal papilla was significantly shorter than the
      mesial papilla at implant-supported crowns, but this difference was not
      significant at the contralateral tooth. A significant relationship between the
      PIS and papilla fill was found. An implant protruding the mucosa in a buccal
      position will result in an increased implant crown length compared to the
      contralateral tooth. Minor buccal angulations of the implant could be corrected
      with customized angulated abutments and did not necessarily result in an
      increased crown length. The distal implant papilla height was obviously shorter,
      although the mesial papilla height was similar to that of the healthy dentition.
      The PIS was found to be a valid index for papilla fill. 

PMID- 24116354
TI  - Role and regulation of heme iron acquisition in gram-negative pathogens.
AB  - Bacteria that reside in animal tissues and/or cells must acquire iron from their
      host. However, almost all of the host iron is sequestered in iron-containing
      compounds and proteins, the majority of which is found within heme molecules.
      Thus, likely iron sources for bacterial pathogens (and non-pathogenic symbionts)
      are free heme and heme-containing proteins. Furthermore, the cellular location of
      the bacterial within the host (intra or extracellular) influences the amount and
      nature of the iron containing compounds available for transport. The low level of
      free iron in the host, coupled with the presence of numerous different heme
      sources, has resulted in a wide range of high-affinity iron acquisition
      strategies within bacteria. However, since excess iron and heme are toxic to
      bacteria, expression of these acquisition systems is highly regulated. Precise
      expression in the correct host environment at the appropriate times enables heme
      iron acquisitions systems to contribute to the growth of bacterial pathogens
      within the host. This mini-review will highlight some of the recent findings in
      these areas for gram-negative pathogens. 

PMID- 24116358
TI  - Effect of the color of intraradicular posts on the color of buccal gingiva: a
      clinical spectophotometric evaluation.
AB  - The primary aim of this study was to test whether intraradicular posts of
      different colors induce different amounts of color change of the buccal gingiva.
      Twentythree patients in need of a post-and-core buildup at one endodontically
      treated incisor, canine, or premolar were included. Titanium (Ti), zirconia (Zi),
      and glass fiber (Gf) posts were consecutively inserted in each test tooth.
      Spectrophotometric color measurement of the buccal gingiva was performed prior to
      post bed preparation and after insertion of Ti, Zi, and Gf posts. For control
      purposes, the gingival color at the contralateral vital tooth was assessed. The
      differences of color components DeltaL, Deltaa, and Deltab and the total color
      difference (DeltaE) between different experimental conditions were obtained.
      DeltaE value of 3.7 was considered the threshold value for intraoral color
      distinction. The gingival thickness at test teeth was measured. No difference
      occurred with regard to the amount of gingival discoloration induced by different
      posts. In the majority of cases, posts did not exhibit a visible influence on the
      color of buccal gingiva. The gingiva at endodontically treated teeth presented a
      visible discoloration compared to the gingiva at vital teeth. The degree of
      gingival discoloration at endodontically treated teeth was correlated with the
      gingival thickness, with more pronounced discolorations in cases of thinner soft
      tissue.

PMID- 24116359
TI  - Two bilateral transposed and infraosseus impacted maxillary canines: a two-step
      combined periodontal and orthodontic approach.
AB  - An extremely rare case presenting two bilateral transposed and infraosseus
      impacted maxillary canines was treated with a combined two-step periodontal and
      orthodontic technique. The canines were transposed mesially and buccally to the
      lateral incisors, close to the midline and in a horizontal position. Direct
      orthodontically guided traction of the teeth toward the center of the alveolar
      ridge was not possible due to the roots of the lateral incisors. The procedure
      consisted of two distinct treatment phases for each side preceded by an initial
      orthodontic treatment to achieve the palatal inclination of the roots of the
      lateral incisors, creating a parallel buccal inclination of the crowns. This
      approach provided a submucosal buccal space into which the canines could be moved
      buccally and distally, avoiding any contact with the roots of the lateral
      incisors. In the first phase, the transposed canines were guided distally. When
      the canines, still in a submucosal position, were freed from those obstacles, the
      second phase was begun. The teeth were exposed, permitting the orthodontically
      guided traction toward the center of the ridge, simulating a proper physiologic
      eruption alignment pattern in the arch. The combined two-step periodontal and
      orthodontic approach used to treat two bilateral transposed and infraosseus
      impacted maxillary canines was extremely successful, resulting in adequate
      alignment in the arch associated with a physiologic sulcus depth, adequate
      keratinized tissue width, and absence of marginal recession at the end of the
      active treatment and 5 years postsurgery. 

PMID- 24116360
TI  - Bone response to dental implants after a 3- to 10-year loading period: a
      histologic and histomorphometric report of four cases.
AB  - The aim of this study was to histologically and histomorphometrically analyze the
      peri-implant tissue reactions and the bone-titanium interface in loaded Ankylos
      implants retrieved after loading periods of longer than 1 year. The archives of
      the Implant Retrieval Center of the Dental School of the University of Chieti-
      Pescara were searched for Ankylos implants retrieved from humans after a loading
      period of longer than 1 year. A total of four implants were found: one had been
      retrieved after 3 years (Friadent plus surface), two after 3.5 years (Friadent
      plus surface), and one after 10 years (Deep Profile surface). All implants had
      been loaded; two had been loaded immediately. One implant was retrieved after
      fracture, one was retrieved after fracture of the superstructure, and the other
      two were retrieved because of bone resorption with or without infection. Compact
      bone with few small marrow spaces was present around the three implants retrieved
      after 3 and 3.5 years; trabecular bone was present around the implant retrieved
      after 10 years. The bone-implant contact of the three best threads was 35% for
      the implant retrieved after 10 years, 99% for the implant retrieved after 3
      years, and 100% for the implants retrieved after 3.5 years. No untoward effects
      were present at the interface, and a high bone-implant contact was present around
      the implants with the microstructured surface. The data show that these implants
      had the potential to maintain osseointegration under long-term function with
      continuous and ongoing bone remodeling. 

PMID- 24116361
TI  - Supracrestal gingival tissue: assessing relation with periodontal biotypes in a
      healthy periodontium.
AB  - This cross-sectional study assessed the variability in supracrestal gingival
      tissue (SGT) dimensions in a healthy periodontium. SGT dimensions were evaluated
      for differences across various locations, tooth types, and periodontal biotypes.
      All measurements were made with a vernier caliper to the nearest 0.1 mm. A total
      of 1,932 sites in 366 teeth were statistically analyzed. Median overall SGT was
      recorded as 3.50 mm with a range from 1.80 to 6.20 mm. The thick-flat biotype
      exhibited greater median SGT than the thinscalloped biotype. When planning crown
      lengthening surgery, periodontal biotype may have a significant role in
      determining SGT dimensions. 

PMID- 24116362
TI  - Long-term implant survival in the grafted maxillary sinus: a systematic review.
AB  - The predictability of maxillary sinus augmentation has been extensively reported.
      Procedural outcomes, most often measured as implant survival rates, have
      customarily used inclusion criteria that included a minimum 1-year loading time.
      The inclusion criteria of this review extended the minimum postloading evaluation
      to 3 years to determine if the previously reported short-term survival rates are
      maintained. An electronic search of the literature was performed and retrieved
      articles were screened using specific inclusion criteria, paramount of which was
      a minimum of 3 years of follow-up. The search revealed 18 articles for the
      lateral window approach (6,500 implants in 2,149 patients) and 7 for the
      transalveolar approach (1,257 implants in 704 patients). Overall, implant
      survival after a minimum of 3 years loading was 93.7% and 97.2% for the lateral
      window and transalveolar approaches, respectively. Of importance is the fact that
      80% of failures occurred within the first year and 93.1% of the failures occurred
      within 3 years. The risk of implant failure after 3 years can now be directly
      calculated as the overall risk of failure after 3 years (6.3%) * the incidence of
      late failures (6.9%), thus equaling 0.43%. This review discredits the theory that
      studies of a lower level of evidence report inflated results when compared with
      prospective randomized controlled clinical trials. 

PMID- 24116363
TI  - A prospective, randomized, controlled, multicenter evaluation of extraction
      socket preservation comparing two bovine xenografts: clinical and histologic
      outcomes.
AB  - The aim of this prospective, randomized, controlled, multicenter study was to
      evaluate and compare the histologic and histomorphometric aspects of extraction
      sockets grafted with two commercially available bovine bone xenografts: Endobon
      (test group) and Bio-Oss (control group). The study was designed to ensure that
      baseline variables between groups were as similar as possible to allow for a
      direct comparison of graft healing characteristics. Thirty-eight patients
      contributed 62 augmented extraction sites to the study. All sites were grafted
      with one type of bovine bone mineral and covered with a resorbable collagen
      membrane for 6 months of healing prior to implant placement surgery. The
      histologic outcomes between the two treatment groups are similar, with de novo
      bone (mean +/- SD) for the test group at 28.5% +/- 20% and for the control group,
      31.4% +/- 18%. Histologic specimens also include membrane remnants. All but two
      implants integrated successfully after 1 year of follow-up. This investigation
      provides support for the efficacy of bovine bone xenograft for socket
      preservation when subsequent implant placement is planned. 

PMID- 24116364
TI  - Guided tissue regeneration using a collagen barrier and bone swaging technique in
      noncontained infrabony defects.
AB  - This clinical study evaluated the effectiveness of guided tissue regeneration
      using a resorbable collagen membrane and bone swaging in noncontained infrabony
      defects by assessing changes in probing pocket depth, probing attachment level,
      and radiographic bone level after 6 months, 1 year, and 2 years. Postsurgical
      clinical and radiographic measurements were statistically significantly different
      from presurgical measurements. The rate of bone fill was positively associated
      with the baseline depth of the bone defect but not associated with the width. The
      noncontained infrabony defects treated with this combined regenerative method
      improved clinically and radiographically. 

PMID- 24116365
TI  - A cone beam tomographic evaluation of hard tissue alterations at immediate
      implants: a clinical prospective study.
AB  - The aim of this study was to investigate the hard tissue alterations of the
      alveolar bone crest following tooth extraction and immediate implant placement
      using cone beam computed tomography. Twelve consecutive patients in need of an
      immediate dental implant were included in the study. An implant of proper length
      was placed in the extraction socket with the coronal margin of the rough surface
      generally flush with or deeper than the buccal alveolar bone crest. All patients
      underwent a radiologic examination both immediately after implant placement (T1)
      and at the time of reentry 4 months after surgery (T2). The survival rate of 12
      immediate implants at 4 months was 100%. Only 9 of 12 patients completed the
      study. The comparison between tomographies performed at T1 and T2 showed
      substantial variations in alveolar bone, mainly at the buccal aspect, registering
      a vertical gain of about 3.2 mm. The horizontal resorption of the alveolar bone
      crest appeared to be more marked at the buccal than at the lingual aspects. At
      the buccal aspect, the resorption was 1.9 mm, 1.0 mm, and 0.6 mm at the
      measurements performed at 1, 3, and 5 mm apical to the crest, respectively. At
      the lingual aspect, the corresponding values were 0.6 mm, 0.7 mm, and 0.5 mm,
      respectively. The bone crest area was more or less the same at T1 and T2, while
      the total area decreased after 4 months of healing but was not statistically
      significant. The results should be viewed with caution because of the small
      number of cases examined. The results confirm the success of immediate implant
      placement. 

PMID- 24116366
TI  - Combination flap surgery with resin-modified glass ionomer for the treatment of
      radicular lesions: a long-term follow-up.
AB  - This retrospective study evaluated the long-term clinical success of combination
      therapy using resin-modified glass ionomer (RMGI) with flap surgery in treating
      subgingival radicular defects. The study population consisted of 142 patients
      with 188 radicular defects. Clinical parameters (pocket depth, recession,
      clinical attachment level [CAL], and bleeding on probing) were evaluated.
      Statistically significant CAL gain was observed from baseline to follow-up in
      successful cases (4.3 +/- 0.1 mm to 4.1 +/- 0.1 mm, respectively; P < .01). RMGI
      with flap surgery demonstrated an overall success rate of 86.7% (77.7% with open
      flap debridement and 94.4% with coronally advanced flap with or without
      connective tissue graft), with favorable and stable clinical results over a mean
      period of 4.2 years (longest follow-up, 13 years). 

PMID- 24116367
TI  - The monocortical window (MCW): a modified split-crest technique adopting ligature
      osteosynthesis.
AB  - Split-crest procedures performed with ultrasonic devices have proven to be a
      viable and effective surgical treatment when the alveolar ridge shows forms of
      resorption in thickness while its height remains virtually unchanged. However, in
      the case of stiff, type 1, corticalized mandibular bone, it may be very difficult
      or even impossible to have any elasticity and lateral augmentation in between the
      split bone walls. Furthermore, a complete detachment of the outer lamellae may
      also occur during expansion maneuvers or during implant insertion. This study
      describes the use of a steel-wire ligature osteosynthesis technique to give
      primary stability both to the expanded cortical window and to the implants
      themselves when they have none at all. This osteosynthesis is simple, quick,
      safe, and bone-saving in force delivery. It is also extremely cheap as well as
      being effective in obtaining ridge expansion, bone regeneration, and implant
      positioning in an all-in-one procedure. This article describes the foundations in
      the literature as well as new elements in the technique. Three short case studies
      are used by way of example. 

PMID- 24116368
TI  - Comparing efficiency and root surface morphology after scaling with Er:YAG and
      Er,Cr:YSGG lasers.
AB  - The purpose of this study was to investigate the root morphology of teeth and
      efficiency of scaling after using Er:YAG and Er,Cr:YSGG lasers. Thirty-two
      periodontally hopeless teeth were extracted. The border of an appropriate
      calculus was marked using a diamond bur on each tooth, and the calculus was
      divided into two almost equal parts. An Er,Cr:YSGG laser with pulse energy of 50
      mJ, power of 1 W, and energy density of 17.7 J/cm2 and an Er:YAG laser with pulse
      energy of 200 mJ, power of 2.4 W, and energy density of 21 J/cm2 were used to
      remove the calculus. The time for scaling was recorded for each group, and using
      stereomicroscopic analysis, the calculus remnant, carbonization, and number of
      craters were investigated. The mean time required for calculus removal in the
      Er,Cr:YSGG and Er:YAG laser groups was 15.22 +/- 6.18 seconds and 7.12 +/- 4.11
      seconds, respectively. The efficiency of calculus removal in the Er:YAG laser
      group was significantly higher than in the Er,Cr:YSGG laser group. Under
      stereomicroscope examination, no carbonization or remaining calculus was found in
      samples from either group, but all samples had craters. The number of craters in
      the Er,Cr:YSGG laser group was significantly higher than in the Er:YAG laser
      group. According to the parameters used and limitations of this study, there was
      no significant difference in efficiency per power for calculus removal between
      the two groups. 

PMID- 24116369
TI  - The effects of laser microgrooves on hard and soft tissue attachment to implant
      collar surfaces: a literature review and interpretation.
AB  - This paper summarizes current knowledge on the benefits of laserablated
      microgrooves in neck regions of endosseous dental implants. Like machine-tooled
      coronal microthreads with particle-blasted surfaces, laser-ablated microgrooves
      help to preserve crestal bone. However, they also appear to uniquely favor a true
      gingival connective tissue attachment comparable to that of natural teeth. 

PMID- 24116370
TI  - Comparison of microstructures between block grafts from the mandibular ramus and
      calvarium for horizontal bone augmentation of the maxilla: a case series study.
AB  - The primary purpose of this clinical study was to compare architectural metric
      parameters using microcomputed tomography (micro-CT) between sites grafted with
      blocks harvested from the mandibular ramus and calvarium for horizontal bone
      augmentation in the maxilla. The second aim was to compare the primary stability
      of implants placed in both types of block grafts. Ten consecutive healthy
      partially edentulous patients requiring extensive horizontal bone reconstruction
      in the maxilla were included. A total of 14 block grafts (7 each from the
      mandibular ramus and calvarium) were studied. After 4 to 6 months of healing, 41
      implants were placed: 24 implants (58.5%) in calvarial (group 1) and 17 (41.5%)
      in ramus grafts (group 2). A resonance frequency analysis (RFA) was performed to
      test implant stability. Furthermore, two biopsy specimens were randomly selected
      for histomorphometric analysis. Micro-CT analyses showed no significant
      difference in the morphometric parametric values analyzed between groups.
      Furthermore, RFA also showed no difference between groups. However, slightly
      higher RFA values were noted for implants placed in ramus grafts. Bone quality,
      as assessed by micro-CT and histomorphometric analyses, was similar in both ramus
      and calvarial block grafts. In addition, there was no difference in primary
      implant stability between groups. 

PMID- 24116371
TI  - Laypersons' perception of facial and dental asymmetries.
AB  - The purpose of this article was to determine the individual visual perception
      thresholds of certain facial and dental discrepancies for a symmetric face model
      (SFM). A facial photograph of a female subject's smile was digitally manipulated
      into an artificially symmetric picture. Modifications were made on the SFM for
      shifts in the dental midline, nose, and chin (group 1) and cants of dental
      midline and incisal plane (group 2), resulting in a total of 24 different images
      divided into two groups. One-hundred randomly selected laypersons divided into
      two groups were used to evaluate each image according to their own personal
      beauty and esthetic criteria using a visual analog scale. The visual perception
      thresholds found for the SFM were 2 mm for a dental midline shift, 4 mm for nose
      deviation, 5 degrees for dental midline cant, and 3 degrees for frontal incisal
      plane cant. Chin deviations of 6 mm or less were not noticed. Dental midline
      shift, nose deviation, dental midline cant, and incisal plane cant relative to an
      SFM have an impact on the perception of facial attractiveness. Chin deviations
      did not have a statistically significant impact. 

PMID- 24116372
TI  - Simultaneous analysis of dopamine and homovanillic acid by high-performance
      liquid chromatography with wall-jet/thin-layer electrochemical detection.
AB  - Wall-jet/thin-layer amperometric electrochemical detection (ECD) coupled with
      high-performance liquid chromatography (HPLC) was used here for the simultaneous
      analysis of dopamine (DA) and homovanillic acid (HVA) at a glassy carbon
      electrode. Compared with the conventional thin-layer mode and wall-jet mode, the
      presented wall-jet/thin-layer ECD has the advantages of enhanced capture of
      electroactive DA and HVA on the working electrode to give enhanced responses and
      more convenient washing/refreshment of the working electrode surface. Under
      optimized conditions, the HPLC-ECD calibration curves show good linearity from
      0.01 to 100 MUM for DA and HVA, and the limits of detection (LODs) obtained were
      1.1 nM for DA and 0.7 nM for HVA which are lower than those obtained with an UV
      vis detector and a commercial electrochemical detector. The method was tested on
      human urine with satisfactory results. The balance of response-signal, signal
      background and noise level for our HPLC-ECD system is also discussed. In
      addition, a demethylation electrooxidation mechanism for HVA is suggested through
      potentiostatic bulk electrolysis, electrospray ionization-mass spectrometry,
      fluorescent spectrophotometry and cyclic voltammetry studies. 

PMID- 24116373
TI  - A protein A modified Au-graphene oxide composite as an enhanced sensing platform
      for SPR-based immunoassay.
AB  - A sensitive and selective wavelength modulation surface plasmon resonance (SPR)
      biosensor is reported with Au nanoparticle decorated graphene oxide (GO) as an
      enhanced sensing platform. GO sheets possess favourable water dispersibility,
      good biocompatibility and high loading capacity. An Au-GO composite with the Au
      spheres size of 15-20 nm was synthesized and modified with staphylococcal protein
      A (SPA). The as-prepared composite assembles directly onto the Au film surface of
      the SPR sensor. Meanwhile, SPA specifically recognizes and binds the Fc portion
      of antibodies, contributing to highly oriented antibody immobilization on the
      chip surface without any antibody modification. Consequently, the biosensor based
      on the SPA modified Au-GO composite exhibits a satisfactory response to rabbit
      IgG in the concentration range of 0.1-50 MUg mL(-1), while the biosensor based on
      the sole SPA layer for antibody immobilization shows a response in the
      concentration range of 1.6-50 MUg mL(-1). Experimental results show that the SPA
      modified Au-GO composite can be successfully used for the signal amplification of
      immunosensors, thereby improving the sensitivity and obviating the need of
      chemical modification of the antibody. 

PMID- 24116374
TI  - Robinson's landmark synthesis of tropinone.
AB  - The 1917 total synthesis of tropinone by Sir Robert Robinson represents a
      landmark achievement in organic synthesis. Decades ahead of its time in terms of
      its retrosynthetic logic and biomimetic approach, the elegant combination of
      these two elements in this synthesis continues to serve as an inspiration for the
      development of new and efficient strategies for complex molecule synthesis. 

PMID- 24116375
TI  - Photocatalytic oxidation of stilbene by self-assembled stacks of manganese
      porphyrins.
AB  - Self-assembled stacks of trimeric manganese porphyrins exhibit high activity in
      the photocatalytic epoxidation of stilbene using O2 as the oxidant. The
      supramolecular structure of the catalyst leads to increased stability of the
      system and enhances the stereoselectivity of the reaction. 

PMID- 24116376
TI  - A new diketopiperazine alkaloid from Aspergillus oryzae.
AB  - Investigation of bioactive secondary metabolites from terrestrial Aspergillus
      oryzae sp. MMAO1 using M2 medium afforded a new diketopiperazine alkaloid, 7,9
      dihydroxy-3-(1H-indol-3-ylmethyl)-8-methoxy-2,3,11,11a-tetrahydro-6H-pyrazino[1,2
      b]isoquinoline-1,4-dione (1a), containing the unusual amino acid L-6,8-dihydroxy
      7-methoxyphenylalanine. This was co-isolated with ditryptophenaline (2), cyclo
      (Tryp,Tyr) (4), cyclo-(Pro,Val), alpha-cyclopiazonic acid (3), kojic acid and
      uridine. Re-cultivation of the fungal strain on Dox medium led to the production
      of bisdethio(bismethylthio)gliotoxin (5), pseurotin A (6) along with linoleic
      acid, alpha-cyclopiazonic acid (3) and kojic acid. The chemical structure of the
      new diketopiperazine alkaloid including the relative configuration was determined
      by 1D and 2D NMR spectroscopy and HR-ESI-MS spectrometry, and by comparison with
      the related literature. The new alkaloid (1a) showed no antimicrobial activity or
      cytotoxicity against brine shrimps.

PMID- 24116377
TI  - Enhancement of cisplatin cytotoxicity in combination with herniarin in vitro.
AB  - Combinatorial chemotherapy is a valuable route, which can be conducted by
      different approaches. Use of cisplatin has been approved by the U.S. Food and
      Drug Administration for different kinds of cancers including bladder cancer.
      Herniarin is a member of simple coumarins, which are a group of common secondary
      metabolites in plants. In this study, the enhancing effects of herniarin on
      cisplatin cytotoxicity were investigated. Cytotoxicity of herniarin on
      transitional cell carcinoma (TCC) cells was first investigated in comparison with
      umbelliferone, the parent compound for a large number of coumarins including
      herniarin, by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) assay. In order to test the effects of herniarin on cisplatin cytotoxicity,
      TCC cells were also treated with various combining concentrations of herniarin
      and cisplatin. In these experiments same amounts of dimethyl sulfoxide were used
      as controls. After 24, 48 and 72 h of treatments, the effects of herniarin on
      cisplatin cytotoxicity were evaluated by MTT assay. The level of chromatin
      condensation which represents the apoptotic morphology was also investigated by
      4',6-diamidino-2-phenylindole (DAPI) staining. Results indicated that unlike
      umbelliferone, its methoxy analog, herniarin, had no significant cytotoxicity on
      TCC cells. On the other hand, the combination of 80 ug/mL herniarin with 5 ug/mL
      cisplatin, significantly enhanced the cytotoxicity of cisplatin. Furtheremore,
      DAPI staining revealed that combining concentrations of herniarin and cisplatin
      resulted in increased chromatin condensation in comparison with controls. This
      study is another confirmation for bioactivity of herniarin and shows that it
      might be a good candidate for further experiments investigating its mechanism of
      action.

PMID- 24116378
TI  - Screen printed flexible radiofrequency identification tag for oxygen monitoring.
AB  - In this work, a radiofrequency identification (RFID) tag with an optical
      indicator for the measurement of gaseous oxygen is described. It consists of an
      O2 sensing membrane of PtOEP together with a full electronic system for RFID
      communication, all printed on a flexible substrate. The membrane is excited by an
      LED at 385 nm wavelength and the intensity of the luminescence generated is
      registered by means of a digital color detector. The output data corresponding to
      the red coordinate of the RGB color space is directly related to the
      concentration of O2, and it is sent to a microcontroller. The RFID tag is
      designed and implemented by screen printing on a flexible substrate for the
      wireless transmission of the measurement to a remote reader. It can operate in
      both active and passive mode, obtaining the power supply from the electromagnetic
      waves of the RFID reader or from a small battery, respectively. This system has
      been fully characterized and calibrated including temperature drifts, showing a
      high-resolution performance that allows measurement of very low values of oxygen
      content. Therefore this system is perfectly suitable for its use in modified
      atmosphere packaging where the oxygen concentration is reduced below 2%. As the
      reading of the O2 concentration inside the envelope is carried out with an
      external RFID reader using wireless communication, there is no need for
      perforations for probes or wires, so the packaging remains completely closed.
      With the presented device, a limit of detection of 40 ppm and a resolution as low
      as 0.1 ppm of O2 can be reached with a low power consumption of 3.55 mA. 

PMID- 24116379
TI  - Reaction under ball-milling: solvent-, ligand-, and metal-free synthesis of
      unsymmetrical diaryl chalcogenides.
AB  - A convenient, efficient, and general procedure for the synthesis of diaryl
      chalcogenides including sulfides, selenides and tellurides has been developed by
      the reaction of diazonium tetrafluoroborates and diaryl dichalcogenides on the
      surface of alumina under ball-milling without any solvent or metal. A wide range
      of functionalized diaryl chalcogenides are obtained in high purity by this
      procedure. 

PMID- 24116380
TI  - Aetiologies of creeping eruption: 78 cases.
AB  - BACKGROUND: Creeping eruption is a migratory linear cutaneous trail. In addition
      to hookworm-related cutaneous larva migrans (HrCLM), other diseases can also be
      revealed by this sign. OBJECTIVES: To report the different aetiologies of
      creeping eruption. METHODS: All consecutive patients with creeping eruption
      presenting to our unit in Pitie Salpetriere Hospital in Paris between 1 March
      2008 and 31 January 2013 were included. The diagnoses were based on microscopic
      data when available (hookworm folliculitis, strongyloidiasis) or the association
      of epidemiological, clinical, biological features and good outcome after specific
      treatment (HrCLM, loiasis, gnathostomiasis). RESULTS: Seventy-four patients (95%)
      presented with HrCLM. All but one had been travelling in a tropical country;
      seven (9%) also presented with folliculitis. Skin scraping of hookworm
      folliculitis lesions was performed in five cases and revealed living nematode
      larvae in three cases. Two patients (3%) with cutaneous gnathostomiasis after
      returning from Bali and Japan presented with intermittent creeping dermatitis on
      the foot and thigh, respectively. One patient (1%), native to Cameroon, was
      diagnosed with loiasis and one patient (1%), with no travel history, presented
      with 'creeping hair'. CONCLUSION: Hookworm-related cutaneous larva migrans
      explains 95% of the cases of creeping eruption; gnathostomiasis, loiasis and
      cutaneous pili migrans may also be diagnosed.

PMID- 24116382
TI  - Synthesis and modular structural architectures of mineralogically inspired novel
      complex Pb oxyhalides.
AB  - Three novel Pb oxyhalides, Pb3[O10Pb20](GeO4)4Cl10 (1),
      [O16Pb22][OPb](OH)I10(I,Br)(H2O) (2), and Pb5.5Si0.5O6Cl (3), have been prepared
      by high-temperature solid-state reactions (1 and 3) and hydrothermal method (2).
      The structure of 1 is based upon novel [O10Pb20](20+) layers of edge- and corner
      sharing oxocentered OPb4 tetrahedra with cavities occupied by the GeO4
      tetrahedral anions. The interlayer space contains low-occupied Pb sites and Cl(-)
      anions. The structure of 2 contains unique [O16Pb22][12+] layers of edge-sharing
      OPb4 tetrahedra with X(-) ions (X = I, Br) in and in between the layers. The
      structure of 3 is the first example of the Pb oxyhalide with the 3:1 ratio
      between the O-Pb and X sheets (X = halide). The unprecedented structure
      topologies and architectures observed in the title compounds are closely related
      to those observed in rare natural Pb oxyhalides that have no synthetic analogues
      to date. 

PMID- 24116381
TI  - Involvement of midkine in neuroblastoma tumourigenesis.
AB  - Midkine is highly expressed in various cancers, including neuroblastoma, one of
      the most malignant paediatric solid tumours known. Also, it has been shown to be
      useful as a tumour marker, a prognosis factor and a target of molecular therapy.
      Several molecular tools (e.g. siRNA, antibodies and RNA aptamer) have been used
      to establish a midkine-targeted therapy. The involvement of midkine in
      tumourigenesis has been demonstrated in vivo in a mouse neuroblastoma model,
      where targeting it with an RNA aptamer was shown to be an effective treatment for
      xenografted tumours. Chemoresistance is one of the notable phenotypes regulated
      by midkine in various cancer cell types. In pancreatic tumours and glioma cells,
      midkine is expressed in chemoresistant cells and is involved in the survival of
      these cells in the presence of anticancer drugs. In contrast to these tumours,
      midkine was found to be expressed in every neuroblastoma cell line tested and the
      knockdown of midkine alone was sufficient to suppress their growth. These results
      indicate that neuroblastoma cells are highly dependent on midkine and that a
      midkine-targeted therapy could exert a significant effect in these cells.
      However, to achieve a midkine-targeted therapy for high-risk neuroblastoma
      patients, the further refinement of the RNA aptamer or antibody as tools and the
      elucidation of midkine signalling are immediate issues that need to be resolved.
      Regarding the latter, although it has been shown that Notch2 functions as a
      receptor in neuroblastoma cells, it is likely that other receptors (e.g.
      anaplastic lymphoma kinase) are also involved in midkine signalling. LINKED
      ARTICLES: This article is part of a themed section on Midkine. To view the other
      articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24116383
TI  - Both male and female novel traits promote the correlated evolution of genitalia
      between the sexes in an arthropod.
AB  - The correlated evolution of genitalia between sexes has been demonstrated in many
      taxa. However, it remains unclear whether female rather than male genitalia can
      play a key role in the correlated evolution of male and female genitalia. We
      conducted an extensive cross-population analysis of the divergence patterns of
      genital structures, weights of whole genital organs, and the bodies of both
      sexes, and male genital length in a group of xystodesmid millipedes showing
      diverse genital morphologies. We demonstrate that the correlated evolution of
      male and female genitalia toward exaggerated states has occurred in the
      millipedes, which have evolved novel traits in both males (forceps-like gonopods)
      and females (retractable bellows). Enlargement and elongation of forceps-like
      gonopods may be advantageous in sperm competition, whereas enlargement and
      elongation of the bellows may facilitate acceptance/rejection of insemination for
      ensuring the female's fitness. These male and female genital parts have affected
      the correlated evolution in the opposite sex, resulting in diversification and
      exaggeration of genital morphology. Our study suggests that evolutionary novel
      traits in not only males but also in females could play an important role in the
      correlated evolution of genitalia between the sexes. 

PMID- 24116385
TI  - Response to hydrostatic pressure of bicellar dispersions containing an anionic
      lipid: pressure-induced interdigitation.
AB  - Bicellar dispersions of chain perdeuterated 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC-d54), 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol)
      (DMPG), and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), with molar ratios
      of 3:1:1, were studied using variable-pressure (2)H NMR spectroscopy at
      hydrostatic pressures up to 125 MPa. Upon warming of the dispersions, spectra at
      ambient pressure indicated a progressive coalescence from small bilayered disks
      undergoing isotropic reorientation to more extended micellar structures in which
      spectra indicated anisotropic reorientation and, under some conditions, magnetic
      orientation and finally to randomly oriented lamellae or multilamellar vesicles.
      Temperatures for the onsets of anisotropic reorientation and random lamellar
      orientation increased with pressure at rates of 0.22 and 0.15  degrees C/MPa,
      respectively. In the 3.5-T magnetic field used for this work, magnetic
      orientation within the intermediate phase was not observed at 83 MPa or higher
      pressures. Comparison of spectra obtained at fixed pressure showed significant
      asymmetry between behaviors upon warming and cooling. For samples of DMPC
      d54/DMPG/DHPC (3:1:1), but not DMPC-d54/DHPC (4:1), a persistent interdigitated
      phase was formed after repeated cooling from high temperature at 83 MPa. This is
      likely a metastable phase and might reflect kinetic trapping of the short-chain
      lipid component, DHPC, in a nonequilibrium spatial distribution as temperature is
      lowered at high pressure. Bicellar dispersions typically behave differently upon
      warming and cooling, and these observations could provide some insight into the
      observed behaviors in such systems. This work also suggests the possibility of
      trapping bicellar dispersions in persistent nonequilibrium morphologies. 

PMID- 24116386
TI  - Migration, national policies, microfinance, and family structure influence
      women's health.

PMID- 24116387
TI  - The impact of molecular dynamics sampling on the performance of virtual screening
      against GPCRs.
AB  - The formation of ligand-protein complexes requires simultaneous adaptation of the
      binding partners. In structure based virtual screening, high throughput docking
      approaches typically consider the ligand flexibility, but the conformational
      freedom of the protein is usually taken into account in a limited way. The goal
      of this study is to elaborate a methodology for incorporating protein flexibility
      to improve the virtual screening enrichments on GPCRs. Explicit-solvated
      molecular dynamics simulations (MD) were carried out in lipid bilayers to
      generate an ensemble of protein conformations for the X-ray structures and
      homology models of both aminergic and peptidergic GPCRs including the chemokine
      CXCR4, dopamine D3, histamine H4, and serotonin 5HT6 holo receptor complexes. The
      quality of the receptor models was assessed by enrichment studies to compare X
      ray structures, homology models, and snapshots from the MD trajectory. According
      to our results, selected frames from the MD trajectory can outperform X-ray
      structures and homology models in terms of enrichment factor and AUC values.
      Significant changes were observed considering EF1% values: comparing the original
      CXCR4, D3, and H4 targets and the additional 5HT6 initial models to that of the
      best MD frame resulted in 0 to 6.7, 0.32 to 3.5 (10*), 13.3 to 26.7 (2*), and 0
      to 14.1 improvements, respectively. It is worth noting that rank-average based
      ensemble evaluation calculated for different ensemble sizes could not improve the
      results further. We propose here that MD simulation can capture protein
      conformations representing the key interacting points of the receptor but less
      biased toward one specific chemotype. These conformations are useful for the
      identification of a "consensus" binding site with improved performance in virtual
      screening. 

PMID- 24116384
TI  - Design and synthesis of curcumin analogues for in vivo fluorescence imaging and
      inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer's
      disease.
AB  - In this article, we first designed and synthesized curcumin-based near-infrared
      (NIR) fluorescence imaging probes for detecting both soluble and insoluble
      amyloid beta (Abeta) species and then an inhibitor that could attenuate cross
      linking of Abeta induced by copper. According to our previous results and the
      possible structural stereohindrance compatibility of the Abeta peptide and the
      hydrophobic/hydrophilic property of the Abeta13-20 (HHQKLVFF) fragment, NIR
      imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58
      showed significant fluorescence property changes upon mixing with both soluble
      and insoluble Abeta species in vitro. In vivo NIR imaging revealed that CRANAD-58
      was capable of differentiating transgenic and wild-type mice as young as 4 months
      old, the age that lacks apparently visible Abeta plaques and Abeta is likely in
      its soluble forms. According to our limited studies on the interaction mechanism
      between CRANAD-58 and Abeta, we also designed CRANAD-17 to attenuate the cross
      linking of Abeta42 induced by copper. It is well-known that the coordination of
      copper with imidazoles on Histidine-13 and 14 (H13, H14) of Abeta peptides could
      initialize covalent cross-linking of Abeta. In CRANAD-17, a curcumin scaffold was
      used as an anchoring moiety to usher the designed compound to the vicinity of H13
      and H14 of Abeta, and imidazole rings were incorporated to compete with H13/H14
      for copper binding. The results of SDS-PAGE gel and Western blot indicated that
      CRANAD-17 was capable of inhibiting Abeta42 cross-linking induced by copper. This
      raises a potential for CRANAD-17 to be considered for AD therapy. 

PMID- 24116389
TI  - Expansion of HIV care and treatment in Yunnan Province, China: treatment outcomes
      with scale up of combination antiretroviral therapy.
AB  - Effective health care models to scale up combination antiretroviral therapy (ART)
      are needed in rural southwestern China. We aimed to evaluate the ART treatment
      outcomes and their associations with patients' demographic characteristics and
      pre-treatment clinical features in a scaled-up provincial ART program serving
      eight heavily HIV-affected prefectures in Yunnan Province. We abstracted
      information from a computerized database for adults initiating ART between July
      2007 and September 2008. Survival functions of mortality and treatment failure
      were calculated by age group, gender, transmission mode, and baseline CD4 count.
      Multivariable Cox regression analyses were conducted to find independent
      associations of various demographic and baseline clinical features with outcome
      variables. Of the 1967 patients in the mortality analysis, there were 110 deaths,
      of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR)
      associated with mortality were greater for patients with baseline CD4 counts <100
      cells/ul vs. patients with CD4 counts >=200 cells/ul, for male vs. female, for
      single vs. married, and for those acquired HIV through injection drug use (IDU)
      vs. other modes of transmission. Successful treatment was 81.3% at six months
      after treatment started. Immunologic treatment failure was associated with
      baseline CD4 counts but not with demographic characteristics. Overall loss to
      follow-up rate was 2.1%. Collaboration between clinics and community networks are
      distinctive features of Yunnan's model for scaling up ART across a diverse, poor,
      and rural population. This study finds that the strategy can succeed even if 40%
      of the patients have a history of IDU. 

PMID- 24116388
TI  - Application of machine learning to proteomics data: classification and biomarker
      identification in postgenomics biology.
AB  - Mass spectrometry is an analytical technique for the characterization of
      biological samples and is increasingly used in omics studies because of its
      targeted, nontargeted, and high throughput abilities. However, due to the large
      datasets generated, it requires informatics approaches such as machine learning
      techniques to analyze and interpret relevant data. Machine learning can be
      applied to MS-derived proteomics data in two ways. First, directly to mass
      spectral peaks and second, to proteins identified by sequence database searching,
      although relative protein quantification is required for the latter. Machine
      learning has been applied to mass spectrometry data from different biological
      disciplines, particularly for various cancers. The aims of such investigations
      have been to identify biomarkers and to aid in diagnosis, prognosis, and
      treatment of specific diseases. This review describes how machine learning has
      been applied to proteomics tandem mass spectrometry data. This includes how it
      can be used to identify proteins suitable for use as biomarkers of disease and
      for classification of samples into disease or treatment groups, which may be
      applicable for diagnostics. It also includes the challenges faced by such
      investigations, such as prediction of proteins present, protein quantification,
      planning for the use of machine learning, and small sample sizes.

PMID- 24116390
TI  - Apoptosis following myocardial infarction: cardiomyocytes and beyond--comment on
      the paper 'Dynamics of serum-induced endothelial cell apoptosis in patients with
      myocardial Infarction' by Forteza et al.

PMID- 24116391
TI  - Central diabetes insipidus revealing neuromeningeal localization of chronic
      myelomonocytic leukaemia.

PMID- 24116392
TI  - "Deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone
      (MDPV) and an examination of effects at the human dopamine transporter.
AB  - Synthetic cathinones, beta-keto analogues of amphetamine (or, more correctly, of
      phenylalkylamines), represent a new and growing class of abused substances.
      Several such analogues have been demonstrated to act as dopamine (DA) releasing
      agents. Methylenedioxypyrovalerone (MDPV) was the first synthetic cathinone shown
      to act as a cocaine-like DA reuptake inhibitor. MDPV and seven deconstructed
      analogues were examined to determine which of MDPV's structural features
      account(s) for uptake inhibition. In voltage-clamped (-60 mV) Xenopus oocytes
      transfected with the human DA transporter (hDAT), all analogues elicited
      inhibitor-like behavior shown as hDAT-mediated outward currents. Using hDAT
      expressing mammalian cells we determined the affinities of MDPV and its analogues
      to inhibit uptake of [3H]DA by hDAT that varied over a broad range (IC50 values
      ca. 135 to >25,000 nM). The methylenedioxy group of MDPV made a minimal
      contribution to affinity, the carbonyl group and a tertiary amine are more
      important, and the extended alpha-alkyl group seems most important. Either a
      tertiary amine, or the extended alpha-alkyl group (but not both), are required
      for the potent nature of MDPV as an hDAT inhibitor.

PMID- 24116393
TI  - Glaucoma drainage implant surgery and ocular surface transplant graft
      preservation.
AB  - Glaucoma may develop or worsen after ocular surface transplantation and often
      requires surgical management for adequate intraocular pressure control.
      Traditional glaucoma filtering procedures in patients with prior ocular surface
      transplant may be problematic for several reasons, which include mechanical
      disruption of the pre-existing graft, epithelial and stem cell toxicity induced
      by antifibrotic agents, and increased risk of future corneal transplantation
      failure. We describe the implantation of a glaucoma drainage implant via a limbal
      based conjunctival incision with tube placement in the ciliary sulcus in three
      eyes of two patients with prior ocular surface transplantation. At a follow-up
      interval of 3-7 months, all three eyes have excellent postoperative control of
      intraocular pressure, stable vision, and healthy ocular surface grafts. 

PMID- 24116394
TI  - Idiopathic acquired true total and subtotal leukonychia: report of two cases.

PMID- 24116395
TI  - Bilateral stereotactic radiofrequency amygdalohippocampectomy for a patient with
      bilateral temporal lobe epilepsy.
AB  - To search for a method for treatment of bilateral temporal lobe epilepsy (BTLE),
      we report one patient with BTLE experienced bilateral stereotactic radiofrequency
      amygdalohippocampectomy (SAHE). Neuropsychological examinations were performed
      before and 5 days, and 6, 18, and 48 months after operation. No seizure occurred
      in the follow-up time, and no long-term memory and intelligence deficits were
      found except for a transient decline of the scores immediately after operation.
      Because severe damage of memory could be caused by bilateral resection surgery,
      bilateral SAHE should be considered as a possible approach for the treatment of
      BTLE. However, further studies with accumulation of cases are needed, especially
      in the detailed assessment of neuropsychological function.

PMID- 24116397
TI  - Isentropic acoustic propagation in a viscous fluid with uniform circular pipeline
      flow.
AB  - Isentropic wave propagation in a viscous fluid with a uniform mean flow confined
      by a rigid-walled circular pipeline is considered. A method based on the Fourier
      Bessel theory, which is complete and orthogonal in Lebesgue space, is introduced
      to solve the convected acoustic equations. After validating the method's
      convergence, the cut-off frequency of wave modes is addressed. Furthermore, the
      effect of flow profile on wave attenuation is analyzed. Meanwhile, measurement
      performance of an ultrasonic flow meter based on wave propagation is numerically
      accounted. 

PMID- 24116396
TI  - A gentle introduction to bayesian analysis: applications to developmental
      research.
AB  - Bayesian statistical methods are becoming ever more popular in applied and
      fundamental research. In this study a gentle introduction to Bayesian analysis is
      provided. It is shown under what circumstances it is attractive to use Bayesian
      estimation, and how to interpret properly the results. First, the ingredients
      underlying Bayesian methods are introduced using a simplified example.
      Thereafter, the advantages and pitfalls of the specification of prior knowledge
      are discussed. To illustrate Bayesian methods explained in this study, in a
      second example a series of studies that examine the theoretical framework of
      dynamic interactionism are considered. In the Discussion the advantages and
      disadvantages of using Bayesian statistics are reviewed, and guidelines on how to
      report on Bayesian statistics are provided. 

PMID- 24116398
TI  - Time reversal communication with a mobile source.
AB  - Broadband underwater acoustic communication signals undergo either a compression
      or dilation in the presence of relative motion between a source and a receiver.
      Consequently, underwater acoustic communications with a mobile source/receiver
      require Doppler compensation through resampling. However, resampling may not be
      necessary when a channel-estimate-based time reversal approach is applied with
      frequent channel updates. Using experimental data (20-30 kHz), it is demonstrated
      that the performance of time reversal communication without resampling is similar
      to the case with resampling, along with the benefit of a modest computational
      saving.

PMID- 24116399
TI  - A steered response power iterative method for high-accuracy acoustic source
      localization.
AB  - Source localization using the steered response power (SRP) usually requires a
      costly grid-search procedure. To address this issue, a modified SRP algorithm was
      recently introduced, providing improved robustness when using coarser spatial
      grids. In this letter, an iterative method based on the modified SRP is
      presented. A coarse spatial grid is initially evaluated with the modified SRP,
      selecting the point with the highest accumulated value. Then, its corresponding
      volume is iteratively decomposed by using a finer spatial grid. Experiments have
      shown that this method provides almost the same accuracy as the fine-grid search
      with a substantial reduction of functional evaluations. 

PMID- 24116400
TI  - The salience of enhanced components within inharmonic complexes.
AB  - A subjective listening task was used to measure the salience of enhanced
      components using typical intensity-enhancement stimuli, time-reversed versions of
      those stimuli, and stimuli which contained a frequency shift of the target
      component. Twenty-five listeners judged whether or not a pitch "stood out" within
      an inharmonic complex. For comparison, judgments also were made for stimuli with
      a single segment that consisted of a simultaneously masked target. The results
      indicate that the perceived salience of enhanced components is greater than might
      be predicted by the effective magnitude of those components, and that
      informational masking is likely involved. 

PMID- 24116401
TI  - Differences in short-term training for interaural phase difference discrimination
      between two different forced-choice paradigms.
AB  - Improvement in interaural phase difference (IPD) discrimination over 2 to 3 h was
      compared for two two-alternative forced-choice paradigms: A three-interval
      paradigm, in which the IPD was in interval two or three, and a paradigm with two
      intervals of four stimuli in which the IPD was in the second and fourth stimuli
      of one interval (AAAA vs ABAB). The difference in performance between the
      beginning and end of the testing period was smaller for the two-interval
      paradigm, supporting the use of this paradigm for fast measurement of
      discrimination thresholds without the need for a long period of training.

PMID- 24116402
TI  - Transformation of body force localized near the surface of a half-space into
      equivalent surface stresses.
AB  - An electromagnetic acoustic transducer (EMAT) or a laser used to generate elastic
      waves in a component is often described as a source of body force confined in a
      layer close to the surface. On the other hand, models for elastic wave radiation
      more efficiently handle sources described as distributions of surface stresses.
      Equivalent surface stresses can be obtained by integrating the body force with
      respect to depth. They are assumed to generate the same field as the one that
      would be generated by the body force. Such an integration scheme can be applied
      to Lorentz force for conventional EMAT configuration. When applied to
      magnetostrictive force generated by an EMAT in a ferromagnetic material, the same
      scheme fails, predicting a null stress. Transforming body force into equivalent
      surface stresses therefore, requires taking into account higher order terms of
      the force moments, the zeroth order being the simple force integration over the
      depth. In this paper, such a transformation is derived up to the second order,
      assuming that body forces are localized at depths shorter than the ultrasonic
      wavelength. Two formulations are obtained, each having some advantages depending
      on the application sought. They apply regardless of the nature of the force
      considered. 

PMID- 24116403
TI  - Use of a porous material description of forests in infrasonic propagation
      algorithms.
AB  - Infrasound can propagate very long distances and remain at measurable levels. As
      a result infrasound sensing is used for remote monitoring in many applications.
      At local ranges, on the order of 10 km, the influence of the presence or absence
      of forests on the propagation of infrasonic signals is considered. Because the
      wavelengths of interest are much larger than the scale of individual components,
      the forest is modeled as a porous material. This approximation is developed
      starting with the relaxation model of porous materials. This representation is
      then incorporated into a Crank-Nicholson method parabolic equation solver to
      determine the relative impacts of the physical parameters of a forest (trunk size
      and basal area), the presence of gaps/trees in otherwise continuous forest/open
      terrain, and the effects of meteorology coupled with the porous layer. Finally,
      the simulations are compared to experimental data from a 10.9 kg blast propagated
      14.5 km. Comparison to the experimental data shows that appropriate inclusion of
      a forest layer along the propagation path provides a closer fit to the data than
      solely changing the ground type across the frequency range from 1 to 30 Hz.

PMID- 24116404
TI  - Infrasonic interferometry of stratospherically refracted microbaroms--a numerical
      study.
AB  - The atmospheric wind and temperature can be estimated through the traveltimes of
      infrasound between pairs of receivers. The traveltimes can be obtained by
      infrasonic interferometry. In this study, the theory of infrasonic interferometry
      is verified and applied to modeled stratospherically refracted waves. Synthetic
      barograms are generated using a raytracing model and taking into account
      atmospheric attenuation, geometrical spreading, and phase shifts due to caustics.
      Two types of source wavelets are implemented for the experiments: blast waves and
      microbaroms. In both numerical experiments, the traveltimes between the receivers
      are accurately retrieved by applying interferometry to the synthetic barograms.
      It is shown that microbaroms can be used in practice to obtain the traveltimes of
      infrasound through the stratosphere, which forms the basis for retrieving the
      wind and temperature profiles. 

PMID- 24116405
TI  - Symmetric airfoil geometry effects on leading edge noise.
AB  - Computational aeroacoustic methods are applied to the modeling of noise due to
      interactions between gusts and the leading edge of real symmetric airfoils.
      Single frequency harmonic gusts are interacted with various airfoil geometries at
      zero angle of attack. The effects of airfoil thickness and leading edge radius on
      noise are investigated systematically and independently for the first time, at
      higher frequencies than previously used in computational methods. Increases in
      both leading edge radius and thickness are found to reduce the predicted noise.
      This noise reduction effect becomes greater with increasing frequency and Mach
      number. The dominant noise reduction mechanism for airfoils with real geometry is
      found to be related to the leading edge stagnation region. It is shown that
      accurate leading edge noise predictions can be made when assuming an inviscid
      meanflow, but that it is not valid to assume a uniform meanflow. Analytic flat
      plate predictions are found to over-predict the noise due to a NACA 0002 airfoil
      by up to 3 dB at high frequencies. The accuracy of analytic flat plate solutions
      can be expected to decrease with increasing airfoil thickness, leading edge
      radius, gust frequency, and Mach number.

PMID- 24116406
TI  - Ocean noise in the tropical and subtropical Pacific Ocean.
AB  - Ocean ambient noise is well studied in the North Pacific and North Atlantic but
      is poorly described for most of the worlds' oceans. Calibrated passive acoustic
      recordings were collected during 2009-2010 at seven locations in the central and
      western tropical and subtropical Pacific. Monthly and hourly mean power spectra
      (15-1000 Hz) were calculated in addition to their skewness, kurtosis, and
      percentile distributions. Overall, ambient noise at these seven sites was 10-20
      dB lower than reported recently for most other locations in the North Pacific. At
      frequencies <100 Hz, spectrum levels were equivalent to those predicted for
      remote or light shipping. Noise levels in the 40 Hz band were compared to the
      presence of nearby and distant ships as reported to the World Meteorological
      Organization Voluntary Observing Ship Scheme (VOS) project. There was a positive,
      but nonsignificant correlation between distant shipping and low frequency noise
      (at 40 Hz). There was a seasonal variation in ambient noise at frequencies >200
      Hz with higher levels recorded in the winter than in the summer. Several species
      of baleen whales, humpback (Megaptera novaeangliae), blue (Balaenoptera
      musculus), and fin (B. physalus) whales, also contributed seasonally to ambient
      noise in characteristic frequency bands.

PMID- 24116407
TI  - Underwater behavior of sperm whales off Kaikoura, New Zealand, as revealed by a
      three-dimensional hydrophone array.
AB  - Observations are presented of the vocal behavior and three dimensional (3D)
      underwater movements of sperm whales measured with a passive acoustic array off
      the coast of Kaikoura, New Zealand. Visual observations and vocal behaviors of
      whales were used to divide dive tracks into different phases, and depths and
      movements of whales are reported for each of these phases. Diving depths and
      movement information from 75 3D tracks of whales in Kaikoura are compared to one
      and two dimensional tracks of whales studied in other oceans. While diving,
      whales in Kaikoura had a mean swimming speed of 1.57 m/s, and, on average, dived
      to a depth of 427 m (SD = 117 m), spending most of their time at depths between
      300 and 600 m. Creak vocalizations, assumed to be the prey capture phase of
      echolocation, occurred throughout the water column from sea surface to sea floor,
      but most occurred at depths of 400-550 m. Three dimensional measurement of
      tracking revealed several different "foraging" strategies, including active
      chasing of prey, lining up slow-moving or unsuspecting prey, and foraging on
      demersal or benthic prey. These movements provide the first 3D descriptions
      underwater behavior of whales at Kaikoura.

PMID- 24116408
TI  - Sound production by the West Australian dhufish (Glaucosoma hebraicum).
AB  - Biological examinations of Glaucosomatid fish species have suggested that they
      could produce sound via swimbladder vibration, using "sonic" muscles. However,
      there have been few reported instances of it in the family. West Australian
      dhufish (Glaucosoma hebraicum) is an iconic teleost, endemic to Western
      Australia. Dissection of G. hebraicum in this study identified the presence of
      "sonic" muscle pairs in immature and sexually mature individuals. The muscle
      tissue originates in the otic region of the skull with its insertion at the
      anterior of the swimbladder. Recordings of sounds were acquired from two male G.
      hebraicum, at a range of 1 m, during capture. Calls comprised 1 to 14 swimbladder
      pulses with spectral peak frequency of 154 +/- 45 Hz (n = 67 calls) and 3 dB
      bandwidth of 110 +/- 50 Hz. The mean of all call maximum source levels was 126 dB
      re 1 MUPa at 1 m with the highest level at 137 dB re 1 MUPa at 1 m. The
      confirmation of sound production by G. hebraicum and the acoustic characteristics
      of those sounds could be used to gain a better understanding of its ecology and,
      particularly, whether the production of sound is associated with specific
      behaviors, such as reproduction.

PMID- 24116409
TI  - Pressure compensated fiber laser hydrophone: modeling and experimentation.
AB  - A pressure compensated metal diaphragm based fiber laser hydrophone configuration
      that can provide good sensitivity, large bandwidth, and sea state zero noise
      floor is proposed in this paper. A simplified theoretical model of the proposed
      sensor configuration is developed in which the acoustic elements of the sensor
      configuration are modeled using a four-pole acoustic transfer matrix and the
      structural elements are modeled as second order single degree of freedom
      elements. This model is then used to optimize the design parameters of the sensor
      system to achieve the performance objectives. An axisymmetric finite element
      analysis of the sensor configuration is also carried out to validate the results
      from the simplified theoretical model. Prototype sensors were fabricated and
      hydrostatic testing in a pressure vessel validated the static pressure
      compensation performance of the sensor. Frequency dependent sensitivity of the
      sensor system was measured through acoustic testing in a water tank. The
      prototype sensor gave a flat frequency response up to 5 kHz and experimental
      results compared well with theoretical predictions. The sensor has an
      acceleration rejection figure on the order of 0 dB ref 1 m/s(2) Pa and the
      pressure compensation approach worked reasonably well up to a hydrostatic
      pressures equivalent to a depth of 50 m.

PMID- 24116410
TI  - Modal density and modal distribution of bending wave vibration fields in ribbed
      plates.
AB  - Plates reinforced by ribs or joists are common elements in lightweight building
      structures, as well as in other engineering structures such as vehicles, ships,
      and aircraft. These structures, however, are often not well suited for simple
      structural acoustic prediction models such as statistical energy analysis. One
      reason is that the modal density is not uniformly distributed due to the spatial
      periodicity introduced by the ribs. This phenomenon is investigated in the
      present paper, using a modal model of a ribbed plate. The modal model uses the
      Fourier sine modes, and the coupling between the plate and ribs is incorporated
      using Hamilton's principle. This model is then used to investigate the modal
      density of the considered spatially periodic structure, and a grouping of the
      modes in different dominating directions is proposed. Suggestions are also given
      regarding how to proceed towards a simplified prediction model for ribbed plates.

PMID- 24116411
TI  - Effect of temporal decay on perception of heavy-weight floor impact sounds.
AB  - This study investigates the effect of temporal decay on perception of heavy
      weight floor impact sounds through auditory experiments. Heavy-weight impact
      sounds were recorded in apartment buildings with a box-framed type reinforced
      concrete structure using a rubber ball. Temporal decay was quantified by using
      the decay rate (DR), defined as the sound pressure level (SPL) decrease per
      second [dB/s], and the distribution of DR for heavy-weight impact sounds was
      calculated. An auditory experiment was conducted in order to examine the just
      noticeable difference (JND) of DR, which was determined by the criteria of 75%
      correct answers by subjects. It was found that the JND of DR is around 11 dB/s.
      Based on the distribution and JND of DR, another experiment was conducted to
      investigate the effect of DR on annoyance perception of heavy-weight floor impact
      sounds in relation to the level differences. The results indicate that SPL and DR
      significantly influence annoyance perception; the scale value of annoyance
      increases with decreasing DR and increasing SPL. It was also found that the
      degree of satisfaction with regards to impact sounds can be improved by
      increasing DR, by controlling the sound field of the receiving room.

PMID- 24116412
TI  - Positioning soundscape research and management.
AB  - This paper is an outcome of a workshop that addressed the question how soundscape
      research can improve its impact on the local level. It addresses a number of
      topics by complementing existing approaches and practices with possible future
      approaches and practices. The paper starts with an analysis of the role of sound
      annoyance and suboptimal soundscapes on the lives of individuals and concludes
      that a good soundscape, or more generally a good sensescape, is at the same time
      pleasant as well as conducive for the adoption of healthy habits. To maintain or
      improve sensescape quality, urban planning needs improved design tools that allow
      for a more holistic optimization and an active role of the local stakeholders.
      Associated with this is a gradual development from government to governance in
      which optimization of the soundscape at a local (administrative or geographic)
      level is directly influenced by the users of spaces. The paper concludes that
      soundscape research can have a greater impact by helping urban planners design
      for health and pleasant experiences as well as developing tools for improved
      citizen involvement in local optimization. 

PMID- 24116413
TI  - Sound exposure of professional orchestral musicians during solitary practice.
AB  - It is broadly acknowledged that professional orchestral musicians risk noise
      induced hearing pathologies due to sound exposure in rehearsal and performance.
      While much has been published regarding orchestral sound levels, little is known
      of the sound exposure these musicians experience during solitary practice,
      despite the many hours they spend engaged in this activity. This study aimed to
      determine sound exposure during solitary practice of 35 professional orchestral
      musicians, representing players of most orchestral instruments. To allow cross
      comparison, participants were assessed playing similar repertoire in a controlled
      environment, recording simultaneously at each ear to determine sound exposure
      levels. Sound levels were recorded between 60 and 107 dB L(Aeq), with peak levels
      between 101 and 130 dB L(C,peak). For average reported practice durations (2.1 h
      per day, five days a week) 53% would exceed accepted permissible daily noise
      exposure in solitary practice, in addition to sound exposure during orchestral
      rehearsals and performances. Significant inter-aural differences were noted in
      violin, viola, flute/piccolo, horn, trombone, and tuba. Only 40% used hearing
      protection at any time while practicing. These findings indicate orchestral
      musicians at risk of noise-induced hearing loss in ensemble face significant
      additional risks during solitary practice. Data presented will enable more
      effective and targeted management strategies for this population.

PMID- 24116414
TI  - Echo thresholds for reflections from acoustically diffusive architectural
      surfaces.
AB  - When sound reflects from an irregular architectural surface, it spreads spatially
      and temporally. Extensive research has been devoted to prediction and measurement
      of diffusion, but less has focused on its perceptual effects. This paper examines
      the effect of temporal diffusion on echo threshold. There are several notable
      differences between the waveform of a reflection identical to the direct sound
      and one from an architectural surface. The onset and offset are damped and the
      energy is spread in time; hence, the reflection response has a lower peak
      amplitude, and is decorrelated from the direct sound. The perceptual consequences
      of these differences are previously undocumented. Echo threshold tests are
      conducted with speech and music signals, using direct sound and a simulated
      reflection that is either identical to the direct sound or has various degrees of
      diffusion. Results indicate that for a speech signal, diffuse reflections are
      less easily detectable as a separate auditory event than specular reflections of
      the same total energy. For a music signal, no differences are observed between
      the echo thresholds for reflections with and without temporal diffusion.
      Additionally, echo thresholds are found to be shorter for speech than for music,
      and shorter for spatialized than for diotic presentation of signals. 

PMID- 24116415
TI  - Relating traffic, construction, and ventilation noise to cognitive performances
      and subjective perceptions.
AB  - The present study investigates the cognitive performance and subjective
      perceptions in the context of road traffic noise alone and multiple noises,
      including construction and ventilation noises. A total of 20 university students
      were exposed to seven noise conditions. Laboratory experiments employed semantic
      and episodic memory tasks. Self-reports of perception were collected from the
      participants. It was found that multiple noise sources impaired the free recall
      of words, and free recall scores were affected by noise type. Significant
      differences in free recall scores were found when the noise level difference
      between the individual noise and multiple noise sources was more than 5 dB. In
      contrast, word comprehension did not mediate the effects of noise on semantic
      memory. Annoyance caused by multiple noise sources correlated highly with the
      results of the free recall and word comprehension tasks. Moreover, loudness and
      roughness were found to account for the annoyance ratings of combinations of road
      traffic noise with construction or ventilation noises.

PMID- 24116416
TI  - Room geometry inference based on spherical microphone array eigenbeam processing.
AB  - The knowledge of parameters characterizing an acoustic environment, such as the
      geometric information about a room, can be used to enhance the performance of
      several audio applications. In this paper, a novel method for three-dimensional
      room geometry inference based on robust and high-resolution beamforming
      techniques for spherical microphone arrays is presented. Unlike other approaches
      that are based on the measurement and processing of multiple room impulse
      responses, here, microphone array signal processing techniques for uncontrolled
      broadband acoustic signals are applied. First, the directions of arrival (DOAs)
      and time differences of arrival (TDOAs) of the direct signal and room reflections
      are estimated using high-resolution robust broadband beamforming techniques and
      cross-correlation analysis. In this context, the main challenges include the low
      reflected-signal to background-noise power ratio, the low energy of reflected
      signals relative to the direct signal, and their strong correlation with the
      direct signal and among each other. Second, the DOA and TDOA information is
      combined to infer the room geometry using geometric relations. The high accuracy
      of the proposed room geometry inference technique is confirmed by experimental
      evaluations based on both simulated and measured data for moderately reverberant
      rooms. 

PMID- 24116417
TI  - Modeling and detection of oil in sea water.
AB  - The challenge of a deep-water oil leak is that a significant quantity of oil
      remains in the water column and possibly changes properties. There is a need to
      quantify the oil settled within the water column and determine its physical
      properties to assist in the oil recovery. There are currently no methods to map
      acoustically submerged oil in the sea. In this paper, high-frequency acoustic
      methods are proposed to localize the oil polluted area and characterize the
      parameters of its spatial covariance, i.e., variance and correlation. A model is
      implemented to study the underlying mechanisms of backscattering due to spatial
      heterogeneity of the medium and predict backscattering returns. An algorithm for
      synthetically generating stationary, Gaussian random fields is introduced which
      provides great flexibility in implementing the physical model of an inhomogeneous
      field with spatial covariance. A method for inference of spatial covariance
      parameters is proposed to describe the scattering field in terms of its second
      order statistics from the backscattered returns. The results indicate that high
      frequency acoustic methods not only are suitable for large-scale detection of oil
      contamination in the water column but also allow inference of the spatial
      covariance parameters resulting in a statistical description of the oil field. 

PMID- 24116418
TI  - Partial differential equation-based localization of a monopole source from a
      circular array.
AB  - Wave source localization from a sensor array has long been the most active
      research topics in both theory and application. In this paper, an explicit and
      time-domain inversion method for the direction and distance of a monopole source
      from a circular array is proposed. The approach is based on a mathematical
      technique, the weighted integral method, for signal/source parameter estimation.
      It begins with an exact form of the source-constraint partial differential
      equation that describes the unilateral propagation of wide-band waves from a
      single source, and leads to exact algebraic equations that include circular
      Fourier coefficients (phase mode measurements) as their coefficients. From them,
      nearly closed-form, single-shot and multishot algorithms are obtained that is
      suitable for use with band-pass/differential filter banks. Numerical evaluation
      and several experimental results obtained using a 16-element circular microphone
      array are presented to verify the validity of the proposed method. 

PMID- 24116419
TI  - Inversions of statistical parameters of an acoustic signal in range-dependent
      environments with applications in ocean acoustic tomography.
AB  - The paper presents an application of a method for the characterization of
      underwater acoustic signals based on the statistics of the wavelet transform sub
      band coefficients in range-dependent environments. As it was illustrated in
      previous work, this statistical characterization scheme is a very efficient tool
      for obtaining observables to be exploited in problems of ocean acoustic
      tomography and geoacoustic inversion, when range-independent environments are
      considered. Now the scheme is applied in range-dependent environments for the
      estimation of range-dependent features in shallow water. A simple denoising
      strategy, also presented in the paper, is shown to enhance the quality of the
      inversion results as it helps to keep the signal characterization to the energy a
      significant part of it. The results presented for typical test cases are
      encouraging and indicative of the potential of the method for the treatment of
      inverse problems in acoustical oceanography. 

PMID- 24116420
TI  - Reconstruction of the free-field radiation from a vibrating structure based on
      measurements in a noisy environment.
AB  - In a noisy environment, the sound field of a source is composed of three parts,
      which are: The field that would be radiated by the target source into free space,
      the incoming field from disturbing sources or reflections, and the scattered
      field that is created by the incoming wave falling on the target source. To
      accurately identify the sound source with nearfield acoustic holography in that
      situation, the last two parts must be removed from the mixed field. In a previous
      study, a method for recovering the free sound field in a noisy environment was
      proposed based on the equivalent source method and measurements of pressure [J.
      Acoust. Soc. Am. 131(2), 1260-1270 (2012)]. In the present paper, that method was
      modified by allowing the input data to be measurements of particle velocity
      instead of pressure. An experiment was carried out to examine both the pressure-
      and velocity-based methods, and the performance of the two methods was compared.
      It was found that both methods are capable of reconstructing the free-field
      pressure radiated by the target source based on measurements made in a noisy
      environment, but the velocity-based method shows a large benefit in the
      reconstruction of the free-field particle velocity. 

PMID- 24116421
TI  - Effect of metabolic presbyacusis on cochlear responses: a simulation approach
      using a physiologically-based model.
AB  - In the presented model, electrical, acoustical, and mechanical elements of the
      cochlea are explicitly integrated into a signal transmission line where these
      elements convey physiological interpretations of the human cochlear structures.
      As a result, this physiologically-motivated model enables simulation of specific
      cochlear lesions such as presbyacusis. The hypothesis is that high-frequency
      hearing loss in older adults may be due to metabolic presbyacusis whereby age
      related cellular/chemical degenerations in the lateral wall of the cochlea cause
      a reduction in the endocochlear potential. The simulations quantitatively confirm
      this hypothesis and emphasize that even if the outer and inner hair cells are
      totally active and intact, metabolic presbyacusis alone can significantly
      deteriorate the cochlear functionality. Specifically, in the model, as the
      endocochlear potential decreases, the transduction mechanism produces less
      receptor current such that there is a reduction in the battery of the somatic
      motor. This leads to a drastic decrease in cochlear amplification and frequency
      sensitivity, as well as changes in position-frequency map (tuning pattern) of the
      cochlea. In addition, the simulations show that the age-related reduction of the
      endocochlear potential significantly inhibits the firing rate of the auditory
      nerve which might contribute to the decline of temporal resolution in the aging
      auditory system. 

PMID- 24116422
TI  - Middle-ear velocity transfer function, cochlear input immittance, and middle-ear
      efficiency in chinchilla.
AB  - The transfer function H(V) between stapes velocity V(S) and sound pressure near
      the tympanic membrane P(TM) is a descriptor of sound transmission through the
      middle ear (ME). The ME power transmission efficiency (MEE), the ratio of sound
      power entering the cochlea to power entering the middle ear, was computed from
      H(V) measured in seven chinchilla ears and previously reported measurements of ME
      input admittance Y(TM) and ME pressure gain G(MEP) [Ravicz and Rosowski, J.
      Acoust. Soc. Am. 132, 2437-2454 (2012); J. Acoust. Soc. Am. 133, 2208-2223
      (2013)] in the same ears. The ME was open, and a pressure sensor was inserted
      into the cochlear vestibule for most measurements. The cochlear input admittance
      Y(C) computed from H(V) and G(MEP) is controlled by a combination of mass and
      resistance and is consistent with a minimum-phase system up to 27 kHz. The real
      part Re{Y(C)}, which relates cochlear sound power to inner-ear sound pressure,
      decreased gradually with frequency up to 25 kHz and more rapidly above that. MEE
      was about 0.5 between 0.1 and 8 kHz, higher than previous estimates in this
      species, and decreased sharply at higher frequencies.

PMID- 24116423
TI  - Nonadditivity of forward and simultaneous masking.
AB  - The current study measured the additional masking obtained for combinations of
      forward and simultaneous maskers as a function of forward masker bandwidth,
      signal delay, and simultaneous masker level. The effects of the two individual
      maskers were equated in all conditions. Additional masking increased with
      increasing masker level, increasing signal delay, and decreasing masker
      bandwidth. The portion of the simultaneous masker that made the greater
      contribution to additional masking was the part that overlapped with the signal,
      not with the forward masker. The changes in additional masking observed as a
      function of forward masker bandwidth and the interaction between the effects of
      forward and simultaneous maskers call into question the use of additional masking
      as a measure of basilar membrane compression and present problems for the use of
      simultaneous noise to simulate hearing loss. 

PMID- 24116424
TI  - Phase effects on the masking of speech by harmonic complexes: variations with
      level.
AB  - Speech reception thresholds were obtained in normally hearing listeners for
      sentence targets masked by harmonic complexes constructed with different phase
      relationships. Maskers had either a constant fundamental frequency (F0), or had
      F0 changing over time, following a pitch contour extracted from natural speech.
      The median F0 of the target speech was very similar to that of the maskers. In
      experiment 1 differences in the masking produced by Schroeder positive and
      Schroeder negative phase complexes were small (around 1.5 dB) for moderate levels
      [60 dB sound pressure level (SPL)], but increased to around 6 dB for maskers at
      80 dB SPL. Phase effects were typically around 1.5 dB larger for maskers that had
      naturally varying F0 contours than for maskers with constant F0. Experiment 2
      showed that shaping the long-term spectrum of the maskers to match the target
      speech had no effect. Experiment 3 included additional phase relationships at
      moderate levels and found no effect of phase. Therefore, the phase relationship
      within harmonic complexes appears to have only minor effects on masking
      effectiveness, at least at moderate levels, and when targets and maskers are in
      the same F0 range.

PMID- 24116425
TI  - Strategies adopted by talkers faced with fluctuating and competing-speech
      maskers.
AB  - Studying how interlocutors exchange information efficiently during conversations
      in less-than-ideal acoustic conditions promises to both further the understanding
      of links between perception and production and inform the design of human
      computer dialogue systems. The current study explored how interlocutors' speech
      changes in the presence of fluctuating noise. Pairs of talkers were recorded
      while solving puzzles cooperatively in quiet and with modulated-noise or
      competing speech maskers whose silent intervals were manipulated to produce
      either temporally sparse or dense maskers. Talkers responded to masked conditions
      by both increasing the amount of speech produced and locally changing their
      speech activity patterns, resulting in a net reduction in the proportion of
      speech in temporal overlap with the maskers, with larger relative reductions for
      sparse maskers. An analysis of talker activity in the vicinity of masker onset
      and offset events showed a significant reduction in onsets following masker
      onsets, and a similar increase in onsets following masker offsets. These findings
      demonstrate that talkers are sensitive to masking noise and respond to its
      fluctuations by adopting a "wait-and-talk" strategy. 

PMID- 24116426
TI  - Behavioral measures of cochlear compression and temporal resolution as predictors
      of speech masking release in hearing-impaired listeners.
AB  - Hearing-impaired (HI) listeners often show less masking release (MR) than normal
      hearing listeners when temporal fluctuations are imposed on a steady-state
      masker, even when accounting for overall audibility differences. This difference
      may be related to a loss of cochlear compression in HI listeners. Behavioral
      estimates of compression, using temporal masking curves (TMCs), were compared
      with MR for band-limited (500-4000 Hz) speech and pure tones in HI listeners and
      age-matched, noise-masked normal-hearing (NMNH) listeners. Compression and pure
      tone MR estimates were made at 500, 1500, and 4000 Hz. The amount of MR was
      defined as the difference in performance between steady-state and 10-Hz square
      wave-gated speech-shaped noise. In addition, temporal resolution was estimated
      from the slope of the off-frequency TMC. No significant relationship was found
      between estimated cochlear compression and MR for either speech or pure tones.
      NMNH listeners had significantly steeper off-frequency temporal masking recovery
      slopes than did HI listeners, and a small but significant correlation was
      observed between poorer temporal resolution and reduced MR for speech. The
      results suggest either that the effects of hearing impairment on MR are not
      determined primarily by changes in peripheral compression, or that the TMC does
      not provide a sufficiently reliable measure of cochlear compression.

PMID- 24116427
TI  - Hearing sensitivity to shifts of rippled-spectrum patterns.
AB  - The sensitivity of human hearing to shifts in rippled spectrum patterns of sound
      was investigated. The test signal was band-limited rippled noise with spectrum
      ripples of various frequency spacing and bandwidth; this type of sound may be
      considered as a quantitatively controlled imitation of complex natural sounds.
      The listener was required to detect a shift in the spectrum ripple phase while
      keeping the other parameters of the noise constant. For cosine-shaped ripples,
      the lowest threshold (1.1%) was found at a ripple frequency of 3.5 ripples per
      octave (rpo), which corresponds to a ripple spacing of 20% of the center
      frequency. The threshold increased for both lower and higher ripple densities.
      Qualitatively similar patterns of threshold dependence on ripple density were
      observed for center frequencies from 1 to 4 kHz. Making the ripples narrower than
      cosine decreased the thresholds to 0.7%-0.75% for ripple densities of 2-5 rpo.
      Keeping the ripple width constant at 3.5%-7.5% of the frequency resulted in a
      monotonic threshold dependence on ripple density: The threshold decreased with
      decreasing density (down to 0.7%). An excitation-pattern model explains
      qualitatively the observed dependence of the ripple-phase shift threshold on
      ripple pattern parameters. 

PMID- 24116428
TI  - Effect of mismatched place-of-stimulation on binaural fusion and lateralization
      in bilateral cochlear-implant users.
AB  - Bilateral cochlear implants (CIs) have provided some success in improving spatial
      hearing abilities to patients, but with large variability in performance. One
      reason for the variability is that there may be a mismatch in the place-of
      stimulation arising from electrode arrays being inserted at different depths in
      each cochlea. Goupell et al. [(2013b). J. Acoust. Soc. Am. 133(4), 2272-2287]
      showed that increasing interaural mismatch led to non-fused auditory images and
      poor lateralization of interaural time differences in normal hearing subjects
      listening to a vocoder. However, a greater bandwidth of activation helped
      mitigate these effects. In the present study, the same experiments were conducted
      in post-lingually deafened bilateral CI users with deliberate and controlled
      interaural mismatch of single electrode pairs. Results show that lateralization
      was still possible with up to 3 mm of interaural mismatch, even when off-center,
      or multiple, auditory images were perceived. However, mismatched inputs are not
      ideal since it leads to a distorted auditory spatial map. Comparison of CI and
      normal hearing listeners showed that the CI data were best modeled by a vocoder
      using Gaussian-pulsed tones with 1.5 mm bandwidth. These results suggest that
      interaural matching of electrodes is important for binaural cues to be maximally
      effective.

PMID- 24116429
TI  - The effect of better-ear glimpsing on spatial release from masking.
AB  - The current experiment investigated whether better-ear glimpsing can explain the
      spatial release achieved by normal-hearing adults when situations are high in
      informational masking. Both modeling and behavioral methods were used. The speech
      reception thresholds of 38 young adults were measured for co-located, spatially
      separated and two better-ear glimpsed conditions. In the better-ear glimpsed
      conditions the binaural signals were processed so that in each time-frequency
      segment, the signal with the better SNR (left or right ear) was presented
      diotically. To investigate the effect of widening auditory filters on better-ear
      glimpsing, adjacent frequency bands were combined in one of the better-ear
      glimpsing conditions. Twenty-two participants were tested with maskers high in
      informational masking, while 16 participants were tested with maskers lower in
      informational masking. The mean speech reception thresholds achieved in the
      glimpsed conditions were significantly worse than in the spatially separated
      condition. This suggests that better-ear glimpsing can explain some but not all
      of the observed spatial release from masking. The difference between performance
      in the spatially separated and glimpsed conditions was largest when informational
      masking was high, suggesting better-ear glimpsing may release energetic rather
      than informational masking. Reducing the number of frequency bands sampled had a
      small effect on performance. 

PMID- 24116430
TI  - Effects of head geometry simplifications on acoustic radiation of vowel sounds
      based on time-domain finite-element simulations.
AB  - One of the key effects to model in voice production is that of acoustic radiation
      of sound waves emanating from the mouth. The use of three-dimensional numerical
      simulations allows to naturally account for it, as well as to consider all
      geometrical head details, by extending the computational domain out of the vocal
      tract. Despite this advantage, many approximations to the head geometry are often
      performed for simplicity and impedance load models are still used as well to
      reduce the computational cost. In this work, the impact of some of these
      simplifications on radiation effects is examined for vowel production in the
      frequency range 0-10 kHz, by means of comparison with radiation from a realistic
      head. As a result, recommendations are given on their validity depending on
      whether high frequency energy (above 5 kHz) should be taken into account or not. 

PMID- 24116431
TI  - Acoustic interaction between the right and left piriform fossae in generating
      spectral dips.
AB  - It is known that the right and left piriform fossae generate two deep dips on
      speech spectra and that acoustic interaction exists in generating the dips: if
      only one piriform fossa is modified, both the dips change in frequency and
      amplitude. In the present study, using a simple geometrical model and measured
      vocal tract shapes, the acoustic interaction was examined by the finite
      difference time-domain method. As a result, one of the two dips was lower in
      frequency than the two independent dips that appeared when either of the piriform
      fossae was occluded, and the other dip was higher in frequency than the two dips.
      At the lower dip frequency, the piriform fossae resonated almost in opposite
      phase, while at the higher dip frequency, they resonated almost in phase. These
      facts indicate that the piriform fossae and the lower part of the pharynx can be
      modeled as a coupled two-oscillator system whose two normal vibration modes
      generate the two spectral dips. When the piriform fossae were identical, only the
      higher dip appeared. This is because the lower mode is not acoustically coupled
      to the main vocal tract enough to generate an absorption dip. 

PMID- 24116432
TI  - Investigating the relationship between average speaker fundamental frequency and
      acoustic vowel space size.
AB  - The purpose of this study is to investigate the potential relationship between
      speaking fundamental frequency and acoustic vowel space size, thus testing a
      possible perceptual source of sex-specific differences in acoustic vowel space
      size based on the greater inter-harmonic spacing and a poorer definition of the
      spectral envelope of higher pitched voices. Average fundamental frequencies and
      acoustic vowel spaces of 56 female German speakers are analyzed. Several
      parameters are used to quantify the size and shape of the vowel space defined by
      /i? epsilon a? [symbol: see text] u?/ such as the area of the polygon spanned by
      the five vowels, the absolute difference in F1 or F2 between /i?/ and /u?/ or
      /a?/, and the Euclidian distance between /i?/ and /a?/. In addition, the
      potential impact of nasality on the vowel space size is examined. Results reveal
      no significant correlation between fundamental frequency and vowel space size
      suggesting other factors must be responsible for the larger female acoustic vowel
      space.

PMID- 24116433
TI  - Acoustic and articulatory analysis of French vowels produced by congenitally
      blind adults and sighted adults.
AB  - In a previous paper [Menard et al., J. Acoust. Soc. Am. 126, 1406-1414 (2009)],
      it was demonstrated that, despite enhanced auditory discrimination abilities for
      synthesized vowels, blind adult French speakers produced vowels that were closer
      together in the acoustic space than those produced by sighted adult French
      speakers, suggesting finer control of speech production in the sighted speakers.
      The goal of the present study is to further investigate the articulatory effects
      of visual deprivation on vowels produced by 11 blind and 11 sighted adult French
      speakers. Synchronous ultrasound, acoustic, and video recordings of the
      participants articulating the ten French oral vowels were made. Results show that
      sighted speakers produce vowels that are spaced significantly farther apart in
      the acoustic vowel space than blind speakers. Furthermore, blind speakers use
      smaller differences in lip protrusion but larger differences in tongue position
      and shape than their sighted peers to produce rounding and place of articulation
      contrasts. Trade-offs between lip and tongue positions were examined. Results are
      discussed in the light of the perception-for-action control theory. 

PMID- 24116435
TI  - Audio-visual speech experience with age influences perceived audio-visual
      asynchrony in speech.
AB  - Previous research indicates that perception of audio-visual (AV) synchrony
      changes in adulthood. Possible explanations for these age differences include a
      decline in hearing acuity, a decline in cognitive processing speed, and increased
      experience with AV binding. The current study aims to isolate the effect of AV
      experience by comparing synchrony judgments from 20 young adults (20 to 30 yrs)
      and 20 normal-hearing middle-aged adults (50 to 60 yrs), an age range for which a
      decline of cognitive processing speed is expected to be minimal. When presented
      with AV stop consonant syllables with asynchronies ranging from 440 ms audio-lead
      to 440 ms visual-lead, middle-aged adults showed significantly less tolerance for
      audio-lead than young adults. Middle-aged adults also showed a greater shift in
      their point of subjective simultaneity than young adults. Natural audio-lead
      asynchronies are arguably more predictable than natural visual-lead asynchronies,
      and this predictability may render audio-lead thresholds more prone to experience
      related fine-tuning.

PMID- 24116434
TI  - The use of confusion patterns to evaluate the neural basis for concurrent vowel
      identification.
AB  - Normal-hearing listeners take advantage of differences in fundamental frequency
      (F0) to segregate competing talkers. Computational modeling using an F0-based
      segregation algorithm and auditory-nerve temporal responses captures the gradual
      improvement in concurrent-vowel identification with increasing F0 difference.
      This result has been taken to suggest that F0-based segregation is the basis for
      this improvement; however, evidence suggests that other factors may also
      contribute. The present study further tested models of concurrent-vowel
      identification by evaluating their ability to predict the specific confusions
      made by listeners. Measured human confusions consisted of at most one to three
      confusions per vowel pair, typically from an error in only one of the two vowels.
      An improvement due to F0 difference was correlated with spectral differences
      between vowels; however, simple models based on acoustic and cochlear spectral
      patterns predicted some confusions not made by human listeners. In contrast, a
      neural temporal model was better at predicting listener confusion patterns.
      However, the full F0-based segregation algorithm using these neural temporal
      analyses was inconsistent across F0 difference in capturing listener confusions,
      being worse for smaller differences. The inability of this commonly accepted
      model to fully account for listener confusions suggests that other factors
      besides F0 segregation are likely to contribute. 

PMID- 24116436
TI  - Just noticeable difference of tone pitch contour change for English- and Chinese
      native listeners.
AB  - Just noticeable differences of tone pitch contour discrimination were examined
      for young English- and Mandarin Chinese-native listeners to examine categorical
      features of tone perception for the two groups of listeners. Three types of
      stimuli were used: A Mandarin Chinese vowel, an English vowel, and tonal glides.
      Level, rising, and falling tones within or across tone boundaries served as the
      standard stimuli to measure thresholds of tone pitch discrimination. Performance
      was equivalent between English- and Chinese-native listeners for level tones, but
      significantly differed for rising and falling tones, regardless of the type of
      stimuli. English listeners showed significantly lower thresholds at the offset of
      F0 shifts than Chinese listeners, while Chinese listeners discriminated tone
      pitch changes at the onset with significantly lower thresholds than their English
      peers. These psychophysical results, combined with tone perception reported in
      other studies, indicated that Mandarin-native listeners perceived lexical tones
      in a categorical manner, based on their lexical tone experience, whereas English
      native listeners perceived tones on a psychophysical base. 

PMID- 24116437
TI  - Vowel identification by cochlear implant users: contributions of static and
      dynamic spectral cues.
AB  - Previous research has shown that normal hearing listeners can identify vowels in
      syllables on the basis of either quasi-static or dynamic spectral cues; however,
      it is not known how well cochlear implant (CI) users with current-generation
      devices can make use of these cues. The present study assessed vowel
      identification in adult CI users and a comparison group of young normal hearing
      (YNH) listeners. Stimuli were naturally spoken /dVd/ syllables and modified
      syllables that retained only quasi-static spectral cues from an 80-ms segment of
      the vowel center ("C80" stimuli) or dynamic spectral cues from two 20-ms segments
      of the vowel edges ("E20" stimuli). YNH listeners exhibited near-perfect
      performance for the unmodified (99.8%) and C80 (92.9%) stimuli and maintained
      good performance for the E20 stimuli (70.2%). CI users exhibited poorer average
      performance than YNH listeners for the Full stimuli (72.3%) and proportionally
      larger reductions in performance for the C80 stimuli (41.8%) and E20 stimuli
      (29.0%). Findings suggest that CI users have difficulty identifying vowels on the
      basis of spectral cues in the absence of duration cues, and have limited access
      to brief dynamic spectral cues. Error analyses suggest that CI users may rely
      strongly on vowel duration cues when those cues are available. 

PMID- 24116439
TI  - Development and evaluation of a linguistically and audiologically controlled
      sentence intelligibility test.
AB  - To allow for a systematic variation of linguistic complexity of sentences while
      acoustically controlling for intelligibility of sentence fragments, a German
      corpus, Oldenburg linguistically and audiologically controlled sentences (OLACS),
      was designed, implemented, and evaluated. Sentences were controlled for
      plausibility with a questionnaire survey. Verification of the speech material was
      performed in three listening conditions (quiet, stationary, and fluctuating
      noise) by collecting speech reception thresholds (SRTs) and response latencies as
      well as individual cognitive measures for 20 young listeners with normal hearing.
      Consistent differences in response latencies across sentence types verified the
      effect of linguistic complexity on processing speed. The addition of noise
      decreased response latencies, giving evidence for different response strategies
      for measurements in noise. Linguistic complexity had a significant effect on SRT.
      In fluctuating noise, this effect was more pronounced, indicating that
      fluctuating noise correlates with stronger cognitive contributions. SRTs in quiet
      correlated with hearing thresholds, whereas cognitive measures explained up to
      40% of the variance in SRTs in noise. In conclusion, OLACS appears to be a
      suitable tool for assessing the interaction between aspects of speech
      understanding (including cognitive processing) and speech intelligibility in
      German. 

PMID- 24116438
TI  - An algorithm to improve speech recognition in noise for hearing-impaired
      listeners.
AB  - Despite considerable effort, monaural (single-microphone) algorithms capable of
      increasing the intelligibility of speech in noise have remained elusive.
      Successful development of such an algorithm is especially important for hearing
      impaired (HI) listeners, given their particular difficulty in noisy backgrounds.
      In the current study, an algorithm based on binary masking was developed to
      separate speech from noise. Unlike the ideal binary mask, which requires prior
      knowledge of the premixed signals, the masks used to segregate speech from noise
      in the current study were estimated by training the algorithm on speech not used
      during testing. Sentences were mixed with speech-shaped noise and with babble at
      various signal-to-noise ratios (SNRs). Testing using normal-hearing and HI
      listeners indicated that intelligibility increased following processing in all
      conditions. These increases were larger for HI listeners, for the modulated
      background, and for the least-favorable SNRs. They were also often substantial,
      allowing several HI listeners to improve intelligibility from scores near zero to
      values above 70%. 

PMID- 24116440
TI  - Emotional speech acoustic model for Malay: iterative versus isolated unit
      training.
AB  - The ability of speech synthesis system to synthesize emotional speech enhances
      the user's experience when using this kind of system and its related
      applications. However, the development of an emotional speech synthesis system is
      a daunting task in view of the complexity of human emotional speech. The more
      recent state-of-the-art speech synthesis systems, such as the one based on hidden
      Markov models, can synthesize emotional speech with acceptable naturalness with
      the use of a good emotional speech acoustic model. However, building an emotional
      speech acoustic model requires adequate resources including segment-phonetic
      labels of emotional speech, which is a problem for many under-resourced
      languages, including Malay. This research shows how it is possible to build an
      emotional speech acoustic model for Malay with minimal resources. To achieve this
      objective, two forms of initialization methods were considered: iterative
      training using the deterministic annealing expectation maximization algorithm and
      the isolated unit training. The seed model for the automatic segmentation is a
      neutral speech acoustic model, which was transformed to target emotion using two
      transformation techniques: model adaptation and context-dependent boundary
      refinement. Two forms of evaluation have been performed: an objective evaluation
      measuring the prosody error and a listening evaluation to measure the naturalness
      of the synthesized emotional speech. 

PMID- 24116441
TI  - Bimodal distribution of performance in discriminating major/minor modes.
AB  - This study investigated the abilities of listeners to classify various sorts of
      musical stimuli as major vs minor. All stimuli combined four pure tones: low and
      high tonics (G5 and G6), dominant (D), and either a major third (B) or a minor
      third (B[symbol: see text]). Especially interesting results were obtained using
      tone-scrambles, randomly ordered sequences of pure tones presented at ~15 per
      second. All tone-scrambles tested comprised 16 G's (G5's + G6's), 8 D's, and
      either 8 B's or 8 B[symbol: see text]'s. The distribution of proportion correct
      across 275 listeners tested over the course of three experiments was strikingly
      bimodal, with one mode very close to chance performance, and the other very close
      to perfect performance. Testing with tone-scrambles thus sorts listeners fairly
      cleanly into two subpopulations. Listeners in subpopulation 1 are sufficiently
      sensitive to major vs minor to classify tone-scrambles nearly perfectly;
      listeners in subpopulation 2 (comprising roughly 70% of the population) have very
      little sensitivity to major vs minor. Skill in classifying major vs minor tone
      scrambles shows a modest correlation of around 0.5 with years of musical
      training.

PMID- 24116442
TI  - Pulse-number discrimination by Cope's gray treefrog (Hyla chrysoscelis) in
      modulated and unmodulated noise.
AB  - In Cope's gray treefrog (Hyla chrysoscelis), thresholds for recognizing
      conspecific calls are lower in temporally modulated noise backgrounds compared
      with unmodulated noise. The effect of modulated noise on discrimination among
      different conspecific calls is unknown. In quiet, females prefer calls with
      relatively more pulses. This study tested the hypotheses that noise impairs
      selectivity for longer calls and that processes akin to dip listening in
      modulated noise can ameliorate this impairment. In two-stimulus choice tests,
      female subjects were allowed to choose between an average-length call and a
      shorter or longer alternative. Tests were replicated at two signal levels in
      quiet and in the presence of chorus-shaped noise that was unmodulated, modulated
      by a sinusoid, or modulated by envelopes resembling natural choruses. When
      subjects showed a preference, it was always for the relatively longer call. Noise
      reduced preferences for longer calls, but the magnitude of this reduction was
      unrelated to whether the noise envelope was modulated or unmodulated. Together,
      the results are inconsistent with the hypothesis that dip listening improves a
      female gray treefrog's ability to select longer calls in modulated compared with
      unmodulated noise. 

PMID- 24116508
TI  - Introduction to special issue on deep water ocean acoustics.

PMID- 24116509
TI  - On horizontal coherence estimates from path integral theory for sound propagation
      through random ocean sound-speed perturbations.
AB  - Previously published results from path integral theory for the horizontal
      coherence length utilized an empirical relation for the phase structure function
      density that was quite different from path integral results obtained for depth
      and time coherence where the phase structure function density was expanded to
      second order in the lag. This letter presents a result for horizontal coherence
      length which carries out the quadratic expansion and analytically solves the
      integral equations. Some simple calculations of horizontal coherence length
      demonstrate the differences between the present and old expressions. In contrast
      to the empirical result the present expression shows the expected one over square
      root range and one over frequency scalings. The results also show more clearly
      how transverse coherence is sensitive to the space-time scales of internal waves
      and other environmental parameters. 

PMID- 24116510
TI  - Coupled mode transport theory for sound transmission through an ocean with random
      sound speed perturbations: coherence in deep water environments.
AB  - Second moments of mode amplitudes at fixed frequency as a function of separations
      in mode number, time, and horizontal distance are investigated using mode-based
      transport equations and Monte Carlo simulation. These second moments are used to
      study full-field acoustic coherence, including depth separations. Calculations
      for low-order modes between 50 and 250 Hz are presented using a deep-water
      Philippine Sea environment. Comparisons between Monte Carlo simulations and
      transport theory for time and depth coherence at frequencies of 75 and 250 Hz and
      for ranges up to 500 km show good agreement. The theory is used to examine the
      accuracy of the adiabatic and quadratic lag approximations, and the range and
      frequency scaling of coherence. It is found that while temporal coherence has a
      dominant adiabatic component, horizontal and vertical coherence have more equal
      contributions from coupling and adiabatic effects. In addition, the quadratic lag
      approximation is shown to be most accurate at higher frequencies and longer
      ranges. Last the range and frequency scalings are found to be sensitive to the
      functional form of the exponential decay of coherence with lag, but temporal and
      horizontal coherence show scalings that fall quite close to the well-known
      inverse frequency and inverse square root range laws.

PMID- 24116511
TI  - Surface gravity waves and their acoustic signatures, 1-30 Hz, on the mid-Pacific
      sea floor.
AB  - In 1999, Duennebier et al. deployed a hydrophone and geophone below the conjugate
      depth in the abyssal Pacific, midway between Hawaii and California. Real time
      data were transmitted for 3 yr over an abandoned ATT cable. These data have been
      analyzed in the frequency band 1 to 30 Hz. Between 1 and 6 Hz, the bottom data
      are interpreted as acoustic radiation from surface gravity waves, an extension to
      higher frequencies of a non-linear mechanism proposed by Longuet-Higgins in 1950
      to explain microseisms. The inferred surface wave spectrum for wave lengths
      between 6 m and 17 cm is saturated (wind-independent) and roughly consistent with
      the traditional Phillips kappa(-4) wave number spectrum. Shorter ocean waves have
      a strong wind dependence and a less steep wave number dependence. Similar
      features are found in the bottom record between 6 and 30 Hz. But this leads to an
      enigma: The derived surface spectrum inferred from the Longuet-Higgins mechanism
      with conventional assumptions for the dispersion relation is associated with mean
      square slopes that greatly exceed those derived from glitter. Regardless of the
      generation mechanism, the measured bottom intensities between 10 and 30 Hz are
      well below minimum noise standards reported in the literature.

PMID- 24116512
TI  - Observations and transport theory analysis of low frequency, acoustic mode
      propagation in the Eastern North Pacific Ocean.
AB  - Second order mode statistics as a function of range and source depth are
      presented from the Long Range Ocean Acoustic Propagation EXperiment (LOAPEX).
      During LOAPEX, low frequency broadband signals were transmitted from a ship
      suspended source to a mode-resolving vertical line array. Over a one-month
      period, the ship occupied seven stations from 50 km to 3200 km distance from the
      receiver. At each station broadband transmissions were performed at a near-axial
      depth of 800 m and an off-axial depth of 350 m. Center frequencies at these two
      depths were 75 Hz and 68 Hz, respectively. Estimates of observed mean mode
      energy, cross mode coherence, and temporal coherence are compared with
      predictions from modal transport theory, utilizing the Garrett-Munk internal wave
      spectrum. In estimating the acoustic observables, there were challenges including
      low signal to noise ratio, corrections for source motion, and small sample sizes.
      The experimental observations agree with theoretical predictions within
      experimental uncertainty.

PMID- 24116513
TI  - Wave-wave interactions and deep ocean acoustics.
AB  - Deep ocean acoustics, in the absence of shipping and wildlife, is driven by
      surface processes. Best understood is the signal generated by non-linear surface
      wave interactions, the Longuet-Higgins mechanism, which dominates from 0.1 to 10
      Hz, and may be significant for another octave. For this source, the spectral
      matrix of pressure and vector velocity is derived for points near the bottom of a
      deep ocean resting on an elastic half-space. In the absence of a bottom, the
      ratios of matrix elements are universal constants. Bottom effects vitiate the
      usual "standing wave approximation," but a weaker form of the approximation is
      shown to hold, and this is used for numerical calculations. In the weak standing
      wave approximation, the ratios of matrix elements are independent of the surface
      wave spectrum, but depend on frequency and the propagation environment. Data from
      the Hawaii-2 Observatory are in excellent accord with the theory for frequencies
      between 0.1 and 1 Hz, less so at higher frequencies. Insensitivity of the
      spectral ratios to wind, and presumably waves, is indeed observed in the data.

PMID- 24116514
TI  - Constructing acoustic timefronts using random matrix theory.
AB  - In a recent letter [Hegewisch and Tomsovic, Europhys. Lett. 97, 34002 (2012)],
      random matrix theory is introduced for long-range acoustic propagation in the
      ocean. The theory is expressed in terms of unitary propagation matrices that
      represent the scattering between acoustic modes due to sound speed fluctuations
      induced by the ocean's internal waves. The scattering exhibits a power-law decay
      as a function of the differences in mode numbers thereby generating a power-law,
      banded, random unitary matrix ensemble. This work gives a more complete account
      of that approach and extends the methods to the construction of an ensemble of
      acoustic timefronts. The result is a very efficient method for studying the
      statistical properties of timefronts at various propagation ranges that agrees
      well with propagation based on the parabolic equation. It helps identify which
      information about the ocean environment can be deduced from the timefronts and
      how to connect features of the data to that environmental information. It also
      makes direct connections to methods used in other disordered waveguide contexts
      where the use of random matrix theory has a multi-decade history. 

PMID- 24116515
TI  - Observations of sound-speed fluctuations in the western Philippine Sea in the
      spring of 2009.
AB  - As an aid to understanding long-range acoustic propagation in the Philippine Sea,
      statistical and phenomenological descriptions of sound-speed variations were
      developed. Two moorings of oceanographic sensors located in the western
      Philippine Sea in the spring of 2009 were used to track constant potential
      density surfaces (isopycnals) and constant potential-temperature surfaces
      (isotherms) in the depth range 120-2000 m. The vertical displacements of these
      surfaces are used to estimate sound-speed fluctuations from internal waves, while
      temperature/salinity variability along isopycnals are used to estimate sound
      speed fluctuations from intrusive structure often termed spice. Frequency spectra
      and vertical covariance functions are used to describe the space-time scales of
      the displacements and spiciness. Internal-wave contributions from diurnal and
      semi-diurnal internal tides and the diffuse internal-wave field [related to the
      Garrett-Munk (GM) spectrum] are found to dominate the sound-speed variability.
      Spice fluctuations are weak in comparison. The internal wave and spice frequency
      spectra have similar form in the upper ocean but are markedly different below 170
      m depth. Diffuse internal-wave mode spectra show a form similar to the GM model,
      while internal-tide mode spectra scale as mode number to the minus two power.
      Spice decorrelates rapidly with depth, with a typical correlation scale of tens
      of meters.

PMID- 24116516
TI  - Long-range asymptotic behavior of vertical travel-time sensitivity kernels.
AB  - Vertical travel-time sensitivity kernels (VTSKs) describe the effect of
      horizontally uniform sound-speed changes on travel times in range-independent
      ocean environments. Wave-theoretic VTSKs can be obtained either analytically,
      through perturbation of the normal-mode representation, or numerically, as
      horizontal marginals of the corresponding two-dimensional and three-dimensional
      travel-time sensitivity kernels. In previous works, it has been observed that
      wave-theoretic finite-frequency VTSKs approach the corresponding ray-theoretic
      sensitivity kernels as the propagation range increases. The present work is an
      attempt to explain this behavior. A stationary-phase approach is used to obtain a
      long-range asymptotic expression for the wave-theoretic VTSKs. The resulting
      asymptotic VTSKs are very close to the corresponding ray-theoretic ones. The
      smoothness condition, required for the stationary-phase approximation to hold, is
      used to obtain an estimate for the range beyond which the asymptotic behavior
      sets in. 

PMID- 24116517
TI  - Using a numerical model to understand the connection between the ocean and
      acoustic travel-time measurements.
AB  - Measurements of acoustic ray travel-times in the ocean provide synoptic integrals
      of the ocean state between source and receiver. It is known that the ray travel
      time is sensitive to variations in the ocean at the transmission time, but the
      sensitivity of the travel-time to spatial variations in the ocean prior to the
      acoustic transmission have not been quantified. This study examines the
      sensitivity of ray travel-time to the temporally and spatially evolving ocean
      state in the Philippine Sea using the adjoint of a numerical model. A one year
      series of five day backward integrations of the adjoint model quantify the
      sensitivity of travel-times to varying dynamics that can alter the travel-time of
      a 611 km ray by 200 ms. The early evolution of the sensitivities reveals high
      mode internal waves that dissipate quickly, leaving the lowest three modes,
      providing a connection to variations in the internal tide generation prior to the
      sample time. They are also strongly sensitive to advective effects that alter
      density along the ray path. These sensitivities reveal how travel-time
      measurements are affected by both nearby and distant waters. Temporal
      nonlinearity of the sensitivities suggests that prior knowledge of the ocean
      state is necessary to exploit the travel-time observations.

PMID- 24116518
TI  - Experimental demonstration of multiuser communication in deep water using time
      reversal.
AB  - Multiuser communication is demonstrated using experimental data (450-550 Hz)
      collected in deep water, south of Japan. The multiple users are spatially
      distributed either in depth or range while a 114-m long, 20-element vertical
      array (i.e., base station) is deployed to around the sound channel axis (~1000
      m). First, signals received separately from ranges of 150 km and 180 km at
      various depths are combined asynchronously to generate multiuser communication
      sequences for subsequent processing, achieving an aggregate data rate of 300
      bits/s for up to three users. Adaptive time reversal is employed to separate
      collided packets at the base station, followed by a single channel decision
      feedback equalizer. Then it is demonstrated that two users separated by 3 km in
      range at ~1000 m depth can transmit information simultaneously to the base
      station at ~500 km range with an aggregate data rate of 200 bits/s.

PMID- 24116519
TI  - Deep water towed array measurements at close range.
AB  - During the North Pacific Acoustic Laboratory Philippine Sea 2009 experiment,
      towed array receptions were made from a towed source as the two ships transited
      from a separation of several Convergence Zones through a Closest Point of
      Approach at 3 km. A combination of narrowband tones and broadband pulses were
      transmitted covering the frequency band 79-535 Hz. The received energy arrives
      from two general paths-direct path and bottom bounce. Bearing-time records of the
      narrowband arrivals at times show a 35 degrees  spread in the angle of arrival of
      the bottom bounce energy. Doppler processing of the tones shows significant
      frequency spread of the bottom bounce energy. Two-dimensional modeling using
      measured bathymetry, a geoacoustic parameterization based upon the geological
      record, and measured sound-speed field was performed. Inclusion of the effects of
      seafloor roughness and surface waves shows that in-plane scattering from rough
      interfaces can explain much of the observed spread in the arrivals. Evidence of
      out-of-plane scattering does exist, however, at short ranges. The amount of out
      of-plane scattering is best observed in the broadband impulse-beam response
      analysis, which in-plane surface roughness modeling cannot explain.

PMID- 24116520
TI  - A numerical model for ocean ultra-low frequency noise: wave-generated acoustic
      gravity and Rayleigh modes.
AB  - The generation of ultra-low frequency acoustic noise (0.1 to 1 Hz) by the
      nonlinear interaction of ocean surface gravity waves is well established. More
      controversial are the quantitative theories that attempt to predict the recorded
      noise levels and their variability. Here a single theoretical framework is used
      to predict the noise level associated with propagating pseudo-Rayleigh modes and
      evanescent acoustic-gravity modes. The latter are dominant only within 200 m from
      the sea surface, in shallow or deep water. At depths larger than 500 m, the
      comparison of a numerical noise model with hydrophone records from two open-ocean
      sites near Hawaii and the Kerguelen islands reveal: (a) Deep ocean acoustic noise
      at frequencies 0.1 to 1 Hz is consistent with the Rayleigh wave theory, in which
      the presence of the ocean bottom amplifies the noise by 10 to 20 dB; (b) in
      agreement with previous results, the local maxima in the noise spectrum support
      the theoretical prediction for the vertical structure of acoustic modes; and (c)
      noise level and variability are well predicted for frequencies up to 0.4 Hz.
      Above 0.6 Hz, the model results are less accurate, probably due to the poor
      estimation of the directional properties of wind-waves with frequencies higher
      than 0.3 Hz.

PMID- 24116521
TI  - Estimating uncertainty in subsurface glider position using transmissions from
      fixed acoustic tomography sources.
AB  - Four acoustic Seagliders were deployed in the Philippine Sea November 2010 to
      April 2011 in the vicinity of an acoustic tomography array. The gliders recorded
      over 2000 broadband transmissions at ranges up to 700 km from moored acoustic
      sources as they transited between mooring sites. The precision of glider
      positioning at the time of acoustic reception is important to resolve the
      fundamental ambiguity between position and sound speed. The Seagliders utilized
      GPS at the surface and a kinematic model below for positioning. The gliders were
      typically underwater for about 6.4 h, diving to depths of 1000 m and traveling on
      average 3.6 km during a dive. Measured acoustic arrival peaks were unambiguously
      associated with predicted ray arrivals. Statistics of travel-time offsets between
      received arrivals and acoustic predictions were used to estimate range
      uncertainty. Range (travel time) uncertainty between the source and the glider
      position from the kinematic model is estimated to be 639 m (426 ms) rms. Least
      squares solutions for glider position estimated from acoustically derived ranges
      from 5 sources differed by 914 m rms from modeled positions, with estimated
      uncertainty of 106 m rms in horizontal position. Error analysis included 70 ms
      rms of uncertainty due to oceanic sound-speed variability.

PMID- 24116522
TI  - Measuring the Kuroshio Current with ocean acoustic tomography.
AB  - Ocean current profiling using ocean acoustic tomography (OAT) was conducted in
      the Kuroshio Current southeast of Taiwan from August 20 to September 15, 2009.
      Sound pulses were transmitted reciprocally between two acoustic stations placed
      near the underwater sound channel axis and separated by 48 km. Based on the
      result of ray simulation, the received signals are divided into multiple ray
      groups because it is difficult to resolve the ray arrivals for individual rays.
      The average differential travel times from these ray groups are used to
      reconstruct the vertical profiles of currents. The currents are estimated with
      respect to the deepest water layer via two methods: An explicit solution and an
      inversion with regularization. The strong currents were confined to the upper 200
      m and rapidly weakened toward 500 m in depth. Both methods give similar results
      and are consistent with shipboard acoustic Doppler current profiler results in
      the upper 150 m. The observed temporal variation demonstrates a similar trend to
      the prediction from the Hybrid Coordinate Ocean Model.

PMID- 24116523
TI  - Estimating the horizontal and vertical direction-of-arrival of water-borne
      seismic signals in the northern Philippine Sea.
AB  - Conventional and adaptive plane-wave beamforming with simultaneous recordings by
      large-aperture horizontal and vertical line arrays during the 2009 Philippine Sea
      Engineering Test (PhilSea09) reveal the rate of occurrence and the two
      dimensional arrival structure of seismic phases that couple into the deep ocean.
      A ship-deployed, controlled acoustic source was used to evaluate performance of
      the horizontal array for a range of beamformer adaptiveness levels. Ninety T
      phases from unique azimuths were recorded between Yeardays 107 to 119. T-phase
      azimuth and S-minus-P-phase time-of-arrival range estimates were validated using
      United States Geological Survey seismic monitoring network data. Analysis of
      phases from a seismic event that occurred on Yearday 112 near the east coast of
      Taiwan approximately 450 km from the arrays revealed a 22 degrees  clockwise
      evolution of T-phase azimuth over 90 s. Two hypotheses to explain such evolution
      body wave excitation of multiple sources or in-water scattering-are presented
      based on T-phase origin sites at the intersection of azimuthal great circle paths
      and ridge/coastal bathymetry. Propagation timing between the source, scattering
      region, and array position suggests the mechanism behind the evolution involved
      scattering of the T-phase from the Ryukyu Ridge and a T-phase
      formation/scattering location estimation error of approximately 3.2 km.

PMID- 24116524
TI  - Long range acoustic measurements of an undersea volcano.
AB  - A seamount 8 km southeast of Sarigan Island erupted on 29 May 2010 and was
      visually observed. The recordings on two sets of hydrophones, operated by
      International Monitoring System (IMS) of the Comprehensive Test Ban Treaty
      Organization (CTBTO) are analyzed. Each array is a triplet of axial single
      hydrophones deployed as a 2 km triangle. Measurements of acoustic intensity for
      the path to the southern triplet are on the order of 6 dB lower than those
      received on the northern triplet. Temporal cross-correlation beamforming
      estimation is performed and the estimated arrival angles for the two arrays, 265
      degrees  and 267 degrees  were consistent with the predicted geodesic arrival of
      264.6 degrees  and 267.8 degrees , respectively. Cross-correlation between single
      phones on the northern and southern arrays reveals a peak at 266 degrees , with a
      cross-correlation of 0.1. Nx2D parabolic equation modeling predicts complete
      blockage due to seamount interaction along the geodesic path. Overprediction of
      the seamount blockage indicates that the 2D approximation is incorrect, and three
      dimensional propagation must be used to explain the observations. This is
      demonstrated by the computation of the Adiabatic Mode Parabolic Equation
      Transmission Loss, which predicts a 5-10 dB lower reception at the southern site.

PMID- 24116525
TI  - Deep seafloor arrivals in long range ocean acoustic propagation.
AB  - Ocean bottom seismometer observations at 5000 m depth during the long-range ocean
      acoustic propagation experiment in the North Pacific in 2004 show robust,
      coherent, late arrivals that are not readily explained by ocean acoustic
      propagation models. These "deep seafloor" arrivals are the largest amplitude
      arrivals on the vertical particle velocity channel for ranges from 500 to 3200
      km. The travel times for six (of 16 observed) deep seafloor arrivals correspond
      to the sea surface reflection of an out-of-plane diffraction from a seamount that
      protrudes to about 4100 m depth and is about 18 km from the receivers. This out
      of-plane bottom-diffracted surface-reflected energy is observed on the deep
      vertical line array about 35 dB below the peak amplitude arrivals and was
      previously misinterpreted as in-plane bottom-reflected surface-reflected energy.
      The structure of these arrivals from 500 to 3200 km range is remarkably robust.
      The bottom-diffracted surface-reflected mechanism provides a means for acoustic
      signals and noise from distant sources to appear with significant strength on the
      deep seafloor.

PMID- 24116526
TI  - Structure and stability of wave-theoretic kernels in the ocean.
AB  - Wave-theoretic modeling can be applied to obtain travel-time sensitivity kernels
      (TSKs) representing the amount ray travel times are affected by sound-speed
      variations anywhere in the medium. This work explores the spatial frequency
      content of the TSK compared to expected ocean variability. It also examines the
      stability of the TSK in environments that produce strong sensitivity of ray paths
      to initial conditions. The conclusion is that the linear TSK model is an
      effective predictor of travel-time changes and that the rays perform nearly as
      well as the full-wave kernel. The TSK is examined in physical space and in
      wavenumber space, and it is found that this is the key to understanding how the
      travel time reacts to ocean perturbations. There are minimum vertical and
      horizontal length scales of ocean perturbations that are required for the travel
      time to be affected. The result is that the correspondence between true travel
      times and those calculated from the kernel is high for large-scale perturbations
      and somewhat less for the small scales. This demonstrates the validity of ray
      based inversion of travel time observations for the cases under study. 

PMID- 24116527
TI  - Reduced rank models for travel time estimation of low order mode pulses.
AB  - Mode travel time estimation in the presence of internal waves (IWs) is a
      challenging problem. IWs perturb the sound speed, which results in travel time
      wander and mode scattering. A standard approach to travel time estimation is to
      pulse compress the broadband signal, pick the peak of the compressed time series,
      and average the peak time over multiple receptions to reduce variance. The peak
      picking approach implicitly assumes there is a single strong arrival and does not
      perform well when there are multiple arrivals due to scattering. This article
      presents a statistical model for the scattered mode arrivals and uses the model
      to design improved travel time estimators. The model is based on an Empirical
      Orthogonal Function (EOF) analysis of the mode time series. Range-dependent
      simulations and data from the Long-range Ocean Acoustic Propagation Experiment
      (LOAPEX) indicate that the modes are represented by a small number of EOFs. The
      reduced-rank EOF model is used to construct a travel time estimator based on the
      Matched Subspace Detector (MSD). Analysis of simulation and experimental data
      show that the MSDs are more robust to IW scattering than peak picking. The
      simulation analysis also highlights how IWs affect the mode excitation by the
      source. 

PMID- 24116528
TI  - Wavefront intensity statistics for 284-Hz broadband transmissions to 107-km range
      in the Philippine Sea: observations and modeling.
AB  - In the spring of 2009, broadband transmissions from a ship-suspended source with
      a 284-Hz center frequency were received on a moored and navigated vertical array
      of hydrophones over a range of 107 km in the Philippine Sea. During a 60-h period
      over 19,000 transmissions were carried out. The observed wavefront arrival
      structure reveals four distinct purely refracted acoustic paths: One with a
      single upper turning point near 80 m depth, two with a pair of upper turning
      points at a depth of roughly 300 m, and one with three upper turning points at
      420 m. Individual path intensity, defined as the absolute square of the center
      frequency Fourier component for that arrival, was estimated over the 60-h
      duration and used to compute scintillation index and log-intensity variance.
      Monte Carlo parabolic equation simulations using internal-wave induced sound
      speed perturbations obeying the Garrett-Munk internal-wave energy spectrum were
      in agreement with measured data for the three deeper-turning paths but differed
      by as much as a factor of four for the near surface-interacting path.

PMID- 24116529
TI  - The North Pacific Acoustic Laboratory deep-water acoustic propagation experiments
      in the Philippine Sea.
AB  - A series of experiments conducted in the Philippine Sea during 2009-2011
      investigated deep-water acoustic propagation and ambient noise in this
      oceanographically and geologically complex region: (i) the 2009 North Pacific
      Acoustic Laboratory (NPAL) Pilot Study/Engineering Test, (ii) the 2010-2011 NPAL
      Philippine Sea Experiment, and (iii) the Ocean Bottom Seismometer Augmentation of
      the 2010-2011 NPAL Philippine Sea Experiment. The experimental goals included (a)
      understanding the impacts of fronts, eddies, and internal tides on acoustic
      propagation, (b) determining whether acoustic methods, together with other
      measurements and ocean modeling, can yield estimates of the time-evolving ocean
      state useful for making improved acoustic predictions, (c) improving our
      understanding of the physics of scattering by internal waves and spice, (d)
      characterizing the depth dependence and temporal variability of ambient noise,
      and (e) understanding the relationship between the acoustic field in the water
      column and the seismic field in the seafloor. In these experiments, moored and
      ship-suspended low-frequency acoustic sources transmitted to a newly developed
      distributed vertical line array receiver capable of spanning the water column in
      the deep ocean. The acoustic transmissions and ambient noise were also recorded
      by a towed hydrophone array, by acoustic Seagliders, and by ocean bottom
      seismometers. 

PMID- 24116530
TI  - T-wave generation and propagation: a comparison between data and spectral element
      modeling.
AB  - T-waves are underwater acoustic waves generated by earthquakes. Modeling of their
      generation and propagation is a challenging problem. Using a spectral element
      code-SPECFEM2D, this paper presents the first realistic simulations of T-waves
      taking into account major aspects of this phenomenon: The radiation pattern of
      the source, the propagation of seismic waves in the crust, the seismic to
      acoustic conversion on a non-planar seafloor, and the propagation of acoustic
      waves in the water column. The simulated signals are compared with data from the
      mid-Atlantic Ridge recorded by an array of hydrophones. The crust/water interface
      is defined by the seafloor bathymetry. Different combinations of water sound
      speed profiles and sub-seafloor seismic velocities, and frequency content of the
      source are tested. The relative amplitudes, main arrival-times, and durations of
      simulated T-phases are in good agreement with the observed data; differences in
      the spectrograms and early arrivals are likely due to too simplistic source
      signals and environmental model. These examples demonstrate the abilities of the
      SPECFEM2D code for modeling earthquake generated T-waves. 

PMID- 24116531
TI  - Weakly dispersive modal pulse propagation in the North Pacific Ocean.
AB  - The propagation of weakly dispersive modal pulses is investigated using data
      collected during the 2004 long-range ocean acoustic propagation experiment
      (LOAPEX). Weakly dispersive modal pulses are characterized by weak dispersion-
      and scattering-induced pulse broadening; such modal pulses experience minimal
      propagation-induced distortion and are thus well suited to communications
      applications. In the LOAPEX environment modes 1, 2, and 3 are approximately
      weakly dispersive. Using LOAPEX observations it is shown that, by extracting the
      energy carried by a weakly dispersive modal pulse, a transmitted communications
      signal can be recovered without performing channel equalization at ranges as long
      as 500 km; at that range a majority of mode 1 receptions have bit error rates
      (BERs) less than 10%, and 6.5% of mode 1 receptions have no errors. BERs are
      estimated for low order modes and compared with measurements of signal-to-noise
      ratio (SNR) and modal pulse spread. Generally, it is observed that larger modal
      pulse spread and lower SNR result in larger BERs.

PMID- 24116532
TI  - Reverberation clutter induced by nonlinear internal waves in shallow water.
AB  - Clutter is related to false alarms for active sonar. It is demonstrated that, in
      shallow water, target-like clutter in reverberation signals can be caused by
      nonlinear internal waves. A nonlinear internal wave is modeled using measured
      stratification on the New Jersey shelf. Reverberation in the presence of the
      internal wave is modeled numerically. Calculations show that acoustic energy
      propagating near a sound speed minimum is deflected as a high intensity, higher
      angle beam into the bottom, where it is backscattered along the reciprocal path.
      The interaction of sound with the internal wave is isolated in space, hence
      resulting in a target-like clutter, which is found to be greater than 10 dB above
      the mean reverberation level.

PMID- 24116533
TI  - Psychometric properties associated with perceived vocal roughness using a
      matching task.
AB  - A psychophysical matching paradigm has been used to better quantify voice quality
      under laboratory conditions. The goals of this study were to establish which of
      two candidate comparison stimuli would best ensure that the range of perceived
      vocal roughness could be adequately bracketed using a matching task and to
      provide a general solution to the problem of estimating vocal roughness.
      Psychometric functions for roughness matching indicated that a speech-like
      sawtooth-plus-noise complex (20 dB signal-to-noise ratio) amplitude modulated by
      a sinusoidal function raised to the 4th power yielded a comparison stimulus with
      a perceptual dynamic range well suited for roughness matching.

PMID- 24116534
TI  - Efficient time of arrival estimation in the presence of multipath propagation.
AB  - Most of acoustical experiments face multipath propagation issues. The times of
      arrival of different ray paths on a sensor can be very close. To estimate them,
      high resolution algorithms have been developed. The main drawback of these
      methods is their need of a full rank spectral matrix of the signals. The
      frequential smoothing technique overcomes this issue by dividing the received
      signal spectrum into several overlapping sub-bands. This division yields a
      transfer matrix that may suffer rank deficiency. In this paper, a new criterion
      to optimally choose the sub-band frequencies is proposed. Encouraging results
      were obtained on real-world data. 

PMID- 24116535
TI  - Frequency-wavenumber processing for infrasound distributed arrays.
AB  - The work described herein discusses the application of a frequency-wavenumber
      signal processing technique to signals from rectangular infrasound arrays for
      detection and estimation of the direction of travel of infrasound. Arrays of 100
      sensors were arranged in square configurations with sensor spacing of 2 m. Wind
      noise data were collected at one site. Synthetic infrasound signals were
      superposed on top of the wind noise to determine the accuracy and sensitivity of
      the technique with respect to signal-to-noise ratio. The technique was then
      applied to an impulsive event recorded at a different site. Preliminary results
      demonstrated the feasibility of this approach. 

PMID- 24116536
TI  - Place specificity measured in forward and interleaved masking in cochlear
      implants.
AB  - Interleaved masking in cochlear implants is analogous to acoustic simultaneous
      masking and is relevant to speech processing strategies that interleave pulses on
      concurrently activated electrodes. In this study, spatial decay of masking as the
      distance between masker and probe increases was compared between forward and
      interleaved masking in the same group of cochlear implant users. Spatial masking
      patterns and the measures of place specificity were similar between forward and
      interleaved masking. Unlike acoustic hearing where broader tuning curves are
      obtained in simultaneous masking, the type of masking experiment did not
      influence the measure of place specificity in cochlear implants. 

PMID- 24116537
TI  - Temporal loudness weights for sounds with increasing and decreasing intensity
      profiles.
AB  - Using molecular psychophysics, temporal loudness weights were measured for 2-s, 1
      kHz tones with flat, increasing and decreasing time-intensity profiles. While
      primacy and recency effects were observed for flat profile stimuli, the so-called
      "level dominance" effect was observed for both increasing and decreasing profile
      stimuli, fully determining their temporal weights. The weighs obtained for these
      profiles were basically zero for all but the most intense parts of these sounds.
      This supports the view that the "level dominance" effect is prominent with
      intensity-varying sounds and that it persists over time since temporal weights
      are not affected by the direction of intensity change. 

PMID- 24116538
TI  - Multiple line arrays for the characterization of aeroacoustic sources using a
      time-reversal method.
AB  - This letter investigates the use of multiple line arrays (LAs) in a Time-Reversal
      Mirror for localizing and characterizing multipole aeroacoustic sources in a
      uniform subsonic mean flow using a numerical Time-Reversal (TR) method.
      Regardless of the original source characteristics, accuracy of predicting the
      source location can be significantly improved using at least two LAs.
      Furthermore, it is impossible to determine the source characteristics using a
      single LA, rather a minimum of two are required to establish either the monopole
      or dipole source nature, while four LAs (fully surrounding the source) are
      required for characterizing a lateral quadrupole source. 

PMID- 24116539
TI  - Loudness of sounds with a subcritical bandwidth: a challenge to current loudness
      models?
AB  - Level differences at equal loudness were measured for bandpass noises centered at
      1.5 kHz with bandwidths from 5 to 405 Hz and a 1.5-kHz pure tone. Irrespective of
      the reference (tone or 135-Hz wide noise), the data indicate a decrease in
      loudness with increasing bandwidth. This is at odds with the assumption of
      stationary loudness models that loudness for sounds with a subcritical bandwidth
      is determined by the intensity and center frequency only. It is also not in
      agreement with dynamic loudness models, which predict higher levels for a tone
      than for equally loud noises, i.e., the opposite effect.

PMID- 24116540
TI  - Estimation of source range using horizontal multipath in continental shelf
      environments.
AB  - A method to estimate source range in environments that exhibit three-dimensional
      propagation effects is presented. A hybrid modeling technique using vertical
      modes and horizontal rays is employed. Results are obtained in a computationally
      efficient manner and require limited knowledge of the environment. The method is
      applied to data recorded on a horizontal line array located 12 km east of the
      southern coast of Florida. The results show an average error of 3.7% in
      estimating the range of an acoustic source located 20 to 63 km away from the
      array.

PMID- 24116541
TI  - Acoustic attenuation performance through a constricted duct improved by an
      annular resonator.
AB  - Acoustic attenuation performance through a constricted duct is greatly improved
      by an annular resonator. A method based on the Green's function for a semi
      infinite circular duct is proposed to calculate the transmission loss, where the
      velocity distributions are assumed to be uniform at the constriction
      inlet/outlets and at the inlet to the annular resonator. From an analogous
      acoustical circuit, the effect of higher order evanescent modes on the quarter
      wave resonance is described by an extra length. The improved acoustic attenuation
      performance is also confirmed by an experiment. 

PMID- 24116542
TI  - Perceived listening effort for a tonal task with contralateral competing signals.
AB  - Perceived listening effort was assessed for a monaural irregular-rhythm detection
      task while competing signals were presented to the contralateral ear. When speech
      was the competing signal, listeners reported greater listening effort compared to
      either contralateral steady-state noise or no competing signal. Behavioral
      thresholds for irregular-rhythm detection were unaffected by competing speech,
      indicating that listeners compensated for this competing signal with effortful
      listening. These results suggest that perceived listening effort may be
      associated with suppression of task-irrelevant information, even for conditions
      where informational masking and competition for linguistic processing resources
      would not be expected. 

PMID- 24116543
TI  - Guyana dolphins (Sotalia guianensis) from Costa Rica emit whistles that vary with
      surface behaviors.
AB  - Guyana dolphins show remarkable intraspecific whistle variation. This variation
      has been largely explained in terms of distance among populations; however, other
      factors such as behavior may also be important. A broadband recording system
      recorded the whistles of Guyana dolphins under three behavioral states. A
      discriminant analysis found that during social and travel events, dolphins emit
      whistles with high delta and minimum frequency, respectively. Whistle duration
      was also important in discriminating behaviors. This study indicates that
      behavior is an important factor contributing to whistle variation of Guyana
      dolphins. Understanding how dolphin whistles vary with behavioral context will
      advance our understanding of dolphin communication and enable appropriate
      comparative studies. 

PMID- 24116544
TI  - Seabed characteristics from ambient noise at three shallow water sites in
      Northern Indian Ocean.
AB  - Ambient noise measurements at three sites along the Indian continental shelf,
      with different water column and seabed, are analyzed to derive vertical
      directionality and further estimation of seabed characteristics. Directionality
      pattern is interpreted using features in the sound speed profiles, in terms of
      noise notch, surface duct, surface bottom reflections, direct arrivals, and high
      bottom loss arrivals. Reflection loss estimated from the field directionality is
      seen to be the same for a particular site and gives an estimate of the sea
      bottom. Seabed characteristics such as critical angle and reflection coefficient
      from field directionality correlate well with theoretical estimation using ground
      truths. 

PMID- 24116545
TI  - Shallow-water acoustic tomography from angle measurements instead of travel-time
      measurements.
AB  - For shallow-water waveguides and mid-frequency broadband acoustic signals, ocean
      acoustic tomography (OAT) is based on the multi-path aspect of wave propagation.
      Using arrays in emission and reception and advanced array processing, every
      acoustic arrival can be isolated and matched to an eigenray that is defined not
      only by its travel time but also by its launch and reception angles. Classically,
      OAT uses travel-time variations to retrieve sound-speed perturbations; this
      assumes very accurate source-to-receiver clock synchronization. This letter uses
      numerical simulations to demonstrate that launch-and-reception-angle tomography
      gives similar results to travel-time tomography without the same requirement for
      high-precision synchronization. 

PMID- 24116546
TI  - Natural triple excitations in local coupled cluster calculations with pair
      natural orbitals.
AB  - In this work, the extension of the previously developed domain based local pair
      natural orbital (DLPNO) based singles- and doubles coupled cluster (DLPNO-CCSD)
      method to perturbatively include connected triple excitations is reported. The
      development is based on the concept of triples-natural orbitals that span the
      joint space of the three pair natural orbital (PNO) spaces of the three electron
      pairs that are involved in the calculation of a given triple-excitation
      contribution. The truncation error is very smooth and can be significantly
      reduced through extrapolation to the zero threshold. However, the extrapolation
      procedure does not improve relative energies. The overall computational effort of
      the method is asymptotically linear with the system size O(N). Actual linear
      scaling has been confirmed in test calculations on alkane chains. The accuracy of
      the DLPNO-CCSD(T) approximation relative to semicanonical CCSD(T0) is comparable
      to the previously developed DLPNO-CCSD method relative to canonical CCSD.
      Relative energies are predicted with an average error of approximately 0.5
      kcal/mol for a challenging test set of medium sized organic molecules. The
      triples correction typically adds 30%-50% to the overall computation time. Thus,
      very large systems can be treated on the basis of the current implementation. In
      addition to the linear C150H302 (452 atoms, >8800 basis functions) we demonstrate
      the first CCSD(T) level calculation on an entire protein, Crambin with 644 atoms,
      and more than 6400 basis functions. 

PMID- 24116547
TI  - On the large interelectronic distance behavior of the correlation factor for
      explicitly correlated wave functions.
AB  - In currently most popular explicitly correlated electronic structure theories,
      the dependence of the wave function on the interelectronic distance rij is built
      via the correlation factor f(r(ij)). While the short-distance behavior of this
      factor is well understood, little is known about the form of f(r(ij)) at large
      r(ij). In this work, we investigate the optimal form of f(r12) on the example of
      the helium atom and helium-like ions and several well-motivated models of the
      wave function. Using the Rayleigh-Ritz variational principle, we derive a
      differential equation for f(r12) and solve it using numerical propagation or
      analytic asymptotic expansion techniques. We found that for every model under
      consideration, f(r12) behaves at large r(ij) as r12(rho)e(Br12) and obtained
      simple analytic expressions for the system dependent values of rho and B. For the
      ground state of the helium-like ions, the value of B is positive, so that f(r12)
      diverges as r12 tends to infinity. The numerical propagation confirms this
      result. When the Hartree-Fock orbitals, multiplied by the correlation factor, are
      expanded in terms of Slater functions r(n)e(-betar), n = 0,...,N, the numerical
      propagation reveals a minimum in f(r12) with depth increasing with N. For the
      lowest triplet state, B is negative. Employing our analytical findings, we
      propose a new "range-separated" form of the correlation factor with the short-
      and long-range r12 regimes approximated by appropriate asymptotic formulas
      connected by a switching function. Exemplary calculations show that this new form
      of f(r12) performs somewhat better than the correlation factors used thus far in
      the standard R12 or F12 theories.

PMID- 24116548
TI  - The multi-layer multi-configuration time-dependent Hartree method for bosons:
      theory, implementation, and applications.
AB  - We develop the multi-layer multi-configuration time-dependent Hartree method for
      bosons (ML-MCTDHB), a variational numerically exact ab initio method for studying
      the quantum dynamics and stationary properties of general bosonic systems. ML
      MCTDHB takes advantage of the permutation symmetry of identical bosons, which
      allows for investigations of the quantum dynamics from few to many-body systems.
      Moreover, the multi-layer feature enables ML-MCTDHB to describe mixed bosonic
      systems consisting of arbitrary many species. Multi-dimensional as well as mixed
      dimensional systems can be accurately and efficiently simulated via the multi
      layer expansion scheme. We provide a detailed account of the underlying theory
      and the corresponding implementation. We also demonstrate the superior
      performance by applying the method to the tunneling dynamics of bosonic ensembles
      in a one-dimensional double well potential, where a single-species bosonic
      ensemble of various correlation strengths and a weakly interacting two-species
      bosonic ensemble are considered. 

PMID- 24116549
TI  - Time-resolved photoelectron imaging spectra from non-adiabatic molecular dynamics
      simulations.
AB  - We present an efficient method for the simulation of time-resolved photoelectron
      imaging (TRPEI) spectra in polyatomic molecules. Our approach combines trajectory
      based molecular dynamics that account for non-adiabatic effects using surface
      hopping, with an approximate treatment of the photoionization process using Dyson
      orbitals as initial and Coulomb waves as final electron states. The method has
      been implemented in the frame of linear response time-dependent density
      functional theory. As an illustration, we simulate time- and energy-resolved
      anisotropy maps for the furan molecule and compare them with recent experimental
      data [T. Fuji, Y.-I. Suzuki, T. Horio, T. Suzuki, R. Mitric, U. Werner, and V.
      Bonacic-Koutecky, J. Chem. Phys. 133, 234303 (2010)]. Our method can be generally
      used for the interpretation of TRPEI experiments allowing to shed light into the
      fundamental photochemical processes in complex molecules.

PMID- 24116550
TI  - General implementation of the resolution-of-the-identity and Cholesky
      representations of electron repulsion integrals within coupled-cluster and
      equation-of-motion methods: theory and benchmarks.
AB  - We present a general implementation of the resolution-of-the-identity (RI) and
      Cholesky decomposition (CD) representations of electron repulsion integrals
      within the coupled-cluster with single and double substitutions (CCSD) and
      equation-of-motion (EOM) family of methods. The CCSD and EOM-CCSD equations are
      rewritten to eliminate the storage of the largest four-index intermediates
      leading to a significant reduction in disk storage requirements, reduced I/O
      penalties, and, as a result, improved parallel performance. In CCSD, the number
      of rate-determining contractions is also reduced; however, in EOM the number of
      operations is increased because the transformed integrals, which are computed
      once in the canonical implementation, need to be reassembled at each Davidson
      iteration. Nevertheless, for large jobs the effect of the increased number of
      rate-determining contractions is surpassed by the significantly reduced memory
      and disk usage leading to a considerable speed-up. Overall, for medium-size
      examples, RI/CD CCSD calculations are approximately 40% faster compared with the
      canonical implementation, whereas timings of EOM calculations are reduced by a
      factor of two. More significant speed-ups are obtained in larger bases, i.e.,
      more than a two-fold speed-up for CCSD and almost five-fold speed-up for EOM-EE
      CCSD in cc-pVTZ. Even more considerable speedups (6-7-fold) are achieved by
      combining RI/CD with the frozen natural orbitals approach. The numeric accuracy
      of RI/CD approaches is benchmarked with an emphasis on energy differences. Errors
      in EOM excitation, ionization, and electron-attachment energies are less than
      0.001 eV with typical RI bases and with a 10(-4) threshold in CD. Errors with 10(
      2) and 10(-3) thresholds, which afford more significant computational savings,
      are less than 0.04 and 0.008 eV, respectively. 

PMID- 24116551
TI  - A hybrid stochastic hierarchy equations of motion approach to treat the low
      temperature dynamics of non-Markovian open quantum systems.
AB  - The hierarchical equations of motion technique has found widespread success as a
      tool to generate the numerically exact dynamics of non-Markovian open quantum
      systems. However, its application to low temperature environments remains a
      serious challenge due to the need for a deep hierarchy that arises from the
      Matsubara expansion of the bath correlation function. Here we present a hybrid
      stochastic hierarchical equation of motion (sHEOM) approach that alleviates this
      bottleneck and leads to a numerical cost that is nearly independent of
      temperature. Additionally, the sHEOM method generally converges with fewer
      hierarchy tiers allowing for the treatment of larger systems. Benchmark
      calculations are presented on the dynamics of two level systems at both high and
      low temperatures to demonstrate the efficacy of the approach. Then the hybrid
      method is used to generate the exact dynamics of systems that are nearly
      impossible to treat by the standard hierarchy. First, exact energy transfer rates
      are calculated across a broad range of temperatures revealing the deviations from
      the Forster rates. This is followed by computations of the entanglement dynamics
      in a system of two qubits at low temperature spanning the weak to strong system
      bath coupling regimes. 

PMID- 24116552
TI  - Heterogeneous nucleation in multi-component vapor on a partially wettable charged
      conducting particle. I. Formulation of general equations: electrical surface and
      line excess quantities.
AB  - Thermodynamics is applied to formulate general equations for internal energies
      and grand potential for a system consisting of a dielectric liquid nucleus of a
      new phase on a charged insoluble conducting sphere within a uniform macroscopic
      one- or multicomponent mother phase. The currently available model for ion
      induced nucleation assumes complete spherical symmetry of the system, implying
      that the seed ion is immediately surrounded by the condensing liquid from all
      sides. We take a step further and treat more realistic geometries, where a cap
      shaped liquid cluster forms on the surface of the seed particle. To take into
      account spontaneous polarization of surface layer molecules we introduce the
      electrical surface and line excess quantities. 

PMID- 24116554
TI  - A unifying mode-coupling theory for transport properties of electrolyte
      solutions. I. General scheme and limiting laws.
AB  - We develop a general method for calculating conduction-diffusion transport
      properties of strong electrolyte mixtures, including specific conductivities,
      steady-state electrophoretic mobilities, and self-diffusion coefficients. The
      ions are described as charged Brownian spheres, and the solvent-mediated
      hydrodynamic interactions (HIs) are also accounted for in the non-instantaneous
      ion atmosphere relaxation effect. A linear response expression relating long-time
      partial mobilities to associated dynamic structure factors is employed in our
      derivation of a general mode coupling theory (MCT) method for the conduction
      diffusion properties. A simplified solution scheme for the MCT method is
      discussed. Analytic results are obtained for transport coefficients of pointlike
      ions which, for very low ion concentrations, reduce to the Deby-Falkenhagen
      Onsager-Fuoss limiting law expressions. As an application, an unusual non
      monotonic concentration dependence of the polyion electrophoretic mobility in a
      mixture of two binary electrolytes is discussed. In addition, leading-order
      extensions of the limiting law results are derived with HIs included. The present
      method complements a related MCT method by the authors for the electrolyte
      viscosity and shear relaxation function [C. Contreras-Aburto and G. Nagele, J.
      Phys.: Condens. Matter 24, 464108 (2012)], so that a unifying scheme for
      conduction-diffusion and viscoelastic properties is obtained. We present here the
      general framework of the method, illustrating its versatility for conditions
      where fully analytic results are obtainable. Numerical results for conduction
      diffusion properties and the viscosity of concentrated electrolytes are presented
      in Paper II [C. Contreras Aburto and G. Nagele, J. Chem. Phys. 139, 134110
      (2013)].

PMID- 24116553
TI  - Heterogeneous nucleation in multi-component vapor on a partially wettable charged
      conducting particle. II. The generalized Laplace, Gibbs-Kelvin, and Young
      equations and application to nucleation.
AB  - Based on the results of a previous paper [M. Noppel, H. Vehkamaki, P. M. Winkler,
      M. Kulmala, and P. E. Wagner, J. Chem. Phys. 139, 134107 (2013)], we derive a
      thermodynamically consistent expression for reversible or minimal work needed to
      form a dielectric liquid nucleus of a new phase on a charged insoluble conducting
      sphere within a uniform macroscopic one- or multicomponent mother phase. The
      currently available model for ion-induced nucleation assumes complete spherical
      symmetry of the system, implying that the seed ion is immediately surrounded by
      the condensing liquid from all sides. We take a step further and treat more
      realistic geometries, where a cap-shaped liquid cluster forms on the surface of
      the seed particle. We derive the equilibrium conditions for such a cluster. The
      equalities of chemical potentials of each species between the nucleus and the
      vapor represent the conditions of chemical equilibrium. The generalized Young
      equation that relates contact angle with surface tensions, surface excess
      polarizations, and line tension, also containing the electrical contribution from
      triple line excess polarization, expresses the condition of thermodynamic
      equilibrium at three-phase contact line. The generalized Laplace equation gives
      the condition of mechanical equilibrium at vapor-liquid dividing surface: it
      relates generalized pressures in neighboring bulk phases at an interface with
      surface tension, excess surface polarization, and dielectric displacements in
      neighboring phases with two principal radii of surface curvature and curvatures
      of equipotential surfaces in neighboring phases at that point. We also re-express
      the generalized Laplace equation as a partial differential equation, which, along
      with electrostatic Laplace equations for bulk phases, determines the shape of a
      nucleus. We derive expressions that are suitable for calculations of the size and
      composition of a critical nucleus (generalized version of the classical Kelvin
      Thomson equation).

PMID- 24116555
TI  - A unifying mode-coupling theory for transport properties of electrolyte
      solutions. II. Results for equal-sized ions electrolytes.
AB  - On the basis of a versatile mode-coupling theory (MCT) method developed in Paper
      I [C. Contreras Aburto and G. Nagele, J. Chem. Phys. 139, 134109 (2013)], we
      investigate the concentration dependence of conduction-diffusion linear transport
      properties for a symmetric binary electrolyte solution. The ions are treated in
      this method as charged Brownian spheres, and the solvent-mediated ion-ion
      hydrodynamic interactions are accounted for also in the ion atmosphere relaxation
      effect. By means of a simplified solution scheme, convenient semi-analytic MCT
      expressions are derived for the electrophoretic mobilities, and the molar
      conductivity, of an electrolyte mixture with equal-sized ions. These expressions
      reduce to the classical Debye-Falkenhagen-Onsager-Fuoss results in the limit of
      very low ion concentration. The MCT expressions are numerically evaluated for a
      binary electrolyte, and compared to experimental data and results by another
      theoretical method. Our analysis encloses, in addition, the electrolyte
      viscosity. To analyze the dynamic influence of the hydration shell, the
      significance of mixed slip-stick hydrodynamic surface boundary conditions, and
      the effect of solvent permeability are explored. For the stick boundary condition
      employed in the hydrodynamic diffusivity tensors, our theoretical results for the
      molar conductivity and viscosity of an aqueous 1:1 electrolyte are in good
      overall agreement with reported experimental data for aqueous NaCl solutions, for
      concentrations extending even up to two molar.

PMID- 24116556
TI  - Efficiency at maximum power of a chemical engine.
AB  - A cyclically operating chemical engine is considered that converts chemical
      energy into mechanical work. The working fluid is a gas of finite-sized spherical
      particles interacting through elastic hard collisions. For a generic transport
      law for particle uptake and release, the efficiency at maximum power eta(mp)
      [corrected] takes the form 1/2+cDeltaMU+O(DeltaMU(2)), with 1/2 a universal
      constant and DeltaMU the chemical potential difference between the particle
      reservoirs. The linear coefficient c is zero for engines featuring a so-called
      left/right symmetry or particle fluxes that are antisymmetric in the applied
      chemical potential difference. Remarkably, the leading constant in eta(mp)
      [corrected] is non-universal with respect to an exceptional modification of the
      transport law. For a nonlinear transport model, we obtain eta(mp) = 1/(theta + 1)
      [corrected], with theta > 0 the power of DeltaMU in the transport equation.

PMID- 24116557
TI  - Solution of the Dirac Coulomb equation for helium-like ions in the Poet-Temkin
      model.
AB  - The Dirac-Coulomb equation for the helium atom is studied under the restrictions
      of the Poet-Temkin model which replaces the 1/r12 interaction by the simplified
      1/r> form. The effective reduction in the dimensionality made it possible to
      obtain binding energies for the singlet and triplet states in this model problem
      with a relative precision from 10(-8) to 10(-10). The energies for the singlet
      state were consistent with a previous configuration interaction calculation [H.
      Tatewaki and Y. Watanabe, Chem. Phys. 389, 58 (2011)]. Manifestations of Brown
      Ravenhall disease were noted at higher values of nuclear charge and ultimately
      limited the accuracy of the Poet-Temkin model energy. The energies from a no-pair
      configuration interaction (CI) calculation (the negative-energy states for the
      appropriate hydrogen-like ion were excluded from the CI expansion) were found to
      be different from the unrestricted B-spline calculation.

PMID- 24116558
TI  - Alternative separation of exchange and correlation energies in multi
      configuration range-separated density-functional theory.
AB  - The alternative separation of exchange and correlation energies proposed by
      Toulouse et al. [Theor. Chem. Acc. 114, 305 (2005)] is explored in the context of
      multi-configuration range-separated density-functional theory. The new
      decomposition of the short-range exchange-correlation energy relies on the
      auxiliary long-range interacting wavefunction rather than the Kohn-Sham (KS)
      determinant. The advantage, relative to the traditional KS decomposition, is that
      the wavefunction part of the energy is now computed with the regular (fully
      interacting) Hamiltonian. One potential drawback is that, because of double
      counting, the wavefunction used to compute the energy cannot be obtained by
      minimizing the energy expression with respect to the wavefunction parameters. The
      problem is overcome by using short-range optimized effective potentials (OEPs).
      The resulting combination of OEP techniques with wavefunction theory has been
      investigated in this work, at the Hartree-Fock (HF) and multi-configuration self
      consistent-field (MCSCF) levels. In the HF case, an analytical expression for the
      energy gradient has been derived and implemented. Calculations have been
      performed within the short-range local density approximation on H2, N2, Li2, and
      H2O. Significant improvements in binding energies are obtained with the new
      decomposition of the short-range energy. The importance of optimizing the short
      range OEP at the MCSCF level when static correlation becomes significant has also
      been demonstrated for H2, using a finite-difference gradient. The implementation
      of the analytical gradient for MCSCF wavefunctions is currently in progress. 

PMID- 24116559
TI  - Solving the Schroedinger equation using Smolyak interpolants.
AB  - In this paper, we present a new collocation method for solving the Schroedinger
      equation. Collocation has the advantage that it obviates integrals. All previous
      collocation methods have, however, the crucial disadvantage that they require
      solving a generalized eigenvalue problem. By combining Lagrange-like functions
      with a Smolyak interpolant, we device a collocation method that does not require
      solving a generalized eigenvalue problem. We exploit the structure of the grid to
      develop an efficient algorithm for evaluating the matrix-vector products required
      to compute energy levels and wavefunctions. Energies systematically converge as
      the number of points and basis functions are increased. 

PMID- 24116560
TI  - Two-component Kramers restricted complete active space self-consistent field
      method with relativistic effective core potential revisited: theory,
      implementation, and applications to spin-orbit splitting of lower p-block atoms.
AB  - The relativistic two-component complete active space self-consistent field theory
      in Kramers restricted formalism (KRCASSCF) through the framework of the spin
      orbit relativistic effective core potential is implemented into the KPACK
      package. This paper continues the development previously reported [Y. S. Kim and
      Y. S. Lee, J. Chem. Phys. 119, 12169 (2003)] and extends the theory by means of
      adding time-reversal symmetry into the relevant expressions so as to complete the
      course of theoretical development. We retained the usage of elementary spinor
      excitation operator for defining the spinor rotation operator and derived the
      gradient and Hessian in simpler forms than previously found. To eliminate
      redundant computation resulting from repeating sums in the derivatives, a
      suitable decomposition method is proposed, which also facilitates the
      implementation. The two-step near second-order approach is employed for
      convergence. The present implementation is applicable for both closed- and open
      shell systems and is used to calculate the atoms of lower p-block. The results
      for 5p and 6p are in good agreement with the experiments, and those for 7p are
      comparable to multi-reference configuration interaction results, showing that
      KRCASSCF is a versatile tool for the relativistic electronic structure
      calculation of molecules containing moderate-weight through superheavy elements. 

PMID- 24116561
TI  - High-precision drop shape analysis on inclining flat surfaces: introduction and
      comparison of this special method with commercial contact angle analysis.
AB  - Drop shape analysis is one of the most important and frequently used methods to
      characterise surfaces in the scientific and industrial communities. An especially
      large number of studies, which use contact angle measurements to analyse
      surfaces, are characterised by incorrect or misdirected conclusions such as the
      determination of surface energies from poorly performed contact angle
      determinations. In particular, the characterisation of surfaces, which leads to
      correlations between the contact angle and other effects, must be critically
      validated for some publications. A large number of works exist concerning the
      theoretical and thermodynamic aspects of two- and tri-phase boundaries. The
      linkage between theory and experiment is generally performed by an axisymmetric
      drop shape analysis, that is, simulations of the theoretical drop profiles by
      numerical integration onto a number of points of the drop meniscus (approximately
      20). These methods work very well for axisymmetric profiles such as those
      obtained by pendant drop measurements, but in the case of a sessile drop onto
      real surfaces, additional unknown and misunderstood effects on the dependence of
      the surface must be considered. We present a special experimental and practical
      investigation as another way to transition from experiment to theory. This
      procedure was developed to be especially sensitive to small variations in the
      dependence of the dynamic contact angle on the surface; as a result, this
      procedure will allow the properties of the surface to be monitored with a higher
      precession and sensitivity. In this context, water drops onto a 111 silicon wafer
      are dynamically measured by video recording and by inclining the surface, which
      results in a sequence of non-axisymmetric drops. The drop profiles are analysed
      by commercial software and by the developed and presented high-precision drop
      shape analysis. In addition to the enhanced sensitivity for contact angle
      determination, this analysis technique, in combination with innovative fit
      algorithms and data presentations, can result in enhanced reproducibility and
      comparability of the contact angle measurements in terms of the material
      characterisation in a comprehensible way. 

PMID- 24116562
TI  - Exploring the dynamics of C/H and C/Cl exchanges in the C(3P) + C2H3Cl reaction.
AB  - The dynamics of the C((3)P) + C2H3Cl reaction at collision energy 3.8 kcal mol(
      1) was investigated in a crossed molecular-beam apparatus using synchrotron
      vacuum-ultraviolet ionization. Time-of-flight spectra of products C3H2Cl, C3H3,
      and Cl were recorded at various laboratory scattering angles, from which
      translational-energy distributions and angular distributions of product channels
      C3H2Cl + H and C3H3 + Cl were derived. Cl correlates satisfactorily with C3H3 in
      linear momentum and angular distributions, which confirms the production of C3H3
      + Cl. The H-loss (Cl-loss) channel has average translational-energy release 14.3
      (8.8) kcal mol(-1) corresponding to a fraction 0.30 (0.14) of available energy
      into the translational degrees of freedom of product HCCCHCl + H (H2CCCH + Cl).
      The branching ratio of channel H to channel Cl was determined approximately as
      12:88. The measurements of translational-energy releases and photoionization
      thresholds cannot distinguish HCCCHCl from H2CCCCl because both isomers have
      similar enthalpy of formation and ionization energy; nevertheless, the Rice
      Ramsperger-Kassel-Marcus calculation prefers HCCCHCl. The measurement of
      photoionization spectra identifies product C3H3 as H2CCCH (propargyl). Both
      products C3H2Cl + H and C3H3 + Cl might correlate to the same triplet
      intermediate H2CCCHCl but have distinct angular distributions; the former is
      nearly isotropic whereas the latter is forward biased. A comparison with the
      C((3)P) + C2H3F reaction is stated. 

PMID- 24116563
TI  - Dissociation of chloromethanes upon resonant sigma* excitation studied by x-ray
      scattering.
AB  - The dissociation process following the Cl K-shell excitation to sigma* resonances
      is studied by high resolution spectroscopy of resonant elastic and inelastic x
      ray scattering on CH3Cl, CH2Cl2, CHCl3, and CCl4 molecules. Calculations
      employing the transition potential and Delta-Kohn-Sham DFT approach are in good
      agreement with the measured total fluorescence yield and show the presence of a
      second quasidegenerate group of states with sigma* character above the lowest
      sigma* unoccupied molecular orbital for molecules with more than one Cl atom. A
      bandwidth narrowing and a nonlinear dispersion behavior is extracted from the
      Kalpha spectral maps for both sigma* resonances. The fitted data indicate that
      the widths of the Franck-Condon distributions for the first and second sigma*
      resonances are comparable for all the molecules under study. In addition, an
      asymmetric broadening of the emission peaks is observed for resonant elastic x
      ray scattering with zero detuning on both sigma* resonances. This is attributed
      to the fast dissociation, transferring about 0.15 of the scattering probability
      into higher vibrational modes.

PMID- 24116564
TI  - The molecular structure of and interconversion tunneling in the argon-cis-1,2
      difluoroethylene complex.
AB  - Guided by ab initio predictions, the structure of the gas-phase complex formed
      between cis-1,2-difluoroethylene and an argon atom in a pulsed molecular jet is
      determined using microwave spectroscopy in the 5.7-21.5 GHz region of the
      spectrum. This is a non-planar, symmetric species, with the argon atom located in
      the FCCF cavity of the difluoroethylene. The transitions in the microwave
      spectrum are observed to be split by an interconversion tunneling motion between
      the two equivalent configurations for the complex with the argon atom located
      either above or below the difluoroethylene molecular plane. Both one- and two
      dimensional discrete variable representation calculations of the tunneling
      splitting using the ab initio interaction potential for the complex suggest that
      the barrier to interconversion is overestimated by theory. 

PMID- 24116565
TI  - High-resolution infrared spectroscopy of atomic bromine in solid parahydrogen and
      orthodeuterium.
AB  - This work extends our earlier investigation of the near-infrared absorption
      spectroscopy of atomic bromine (Br) trapped in solid parahydrogen (pH2) and
      orthodeuterium (oD2) [S. C. Kettwich, L. O. Paulson, P. L. Raston, and D. T.
      Anderson, J. Phys. Chem. A 112, 11153 (2008)]. We report new spectroscopic
      observations on a series of double transitions involving excitation of the weak
      Br-atom spin-orbit (SO) transition ((2)P(1/2) <- (2)P(3/2)) in concert with
      phonon, rotational, vibrational, and rovibrational excitation of the solid
      molecular hydrogen host. Further, we utilize the rapid vapor deposition technique
      to produce pH2 crystals with a non-equilibrium mixture of face centered cubic
      (fcc) and hexagonal closed packed (hcp) crystal domains in the freshly deposited
      solid. Gentle annealing (T = 4.3 K) of the pH2 sample irreversibly converts the
      higher energy fcc crystal domains to the slightly more stable hcp structure. We
      follow the extent of this conversion process using the intensity of the U1(0)
      transition of solid pH2 and correlate crystal structure changes with changes in
      the integrated intensity of Br-atom absorption features. Annealing the pH2 solid
      causes the integrated intensity of the zero-phonon Br SO transition to increase
      approximately 45% to a value that is 8 times larger than the gas phase value. We
      show that the magnitude of the increase is strongly correlated to the fraction of
      hcp crystal domains within the solid. Theoretical calculations presented in Paper
      II show that these intensity differences are caused by the different symmetries
      of single substitution sites for these two crystal structures. For fully annealed
      Br-atom doped pH2 solids, where the crystal structure is nearly pure hcp, the Br
      atom SO transition sharpens considerably and shows evidence for resolved
      hyperfine structure.

PMID- 24116566
TI  - Infrared-active spin-orbit transitions of halogen atom dopants in solid
      parahydrogen: the role of trapping site geometry.
AB  - We present theoretical calculations of the (2)P(1/2) <- (2)P(3/2) spin-orbit
      transition of Cl dopants embedded as substitutional impurities in solid
      parahydrogen (pH2) matrices. In the lower-energy (2)P(3/2) spin-orbit level, the
      Cl atom's electron density distribution is anisotropic, and slightly distorts the
      geometry of the atom's trapping site. This distortion leads to a blue shift in
      the spin-orbit transition energy; the blue shift is enhanced when we account for
      the large-amplitude zero point motions of the pH2 molecules surrounding the Cl
      dopant. We also show that the intensity of the transition depends on the geometry
      of the trapping site. In the gas phase, the (2)P(1/2) <- (2)P(3/2) atomic
      transition is electric dipole forbidden. However, when the Cl atom resides in
      trapping sites that mimic the hexagonal close packed morphology of pure solid
      pH2, the transition becomes electric dipole allowed through interaction-induced
      transition dipole moments. These transition dipole moments originate in the
      anisotropic electron density distribution of the lower-energy (2)P(3/2) spin
      orbit level.

PMID- 24116567
TI  - Selective coherent control of the lifetime of a resonance state with laser
      pulses.
AB  - It is shown that new possibilities for control of the lifetime of a system in a
      resonance state emerge when the density of resonances overlapping and interfering
      with the target resonance increases. When using a control scheme combining two
      pump laser pulses, it is found that increasing the density of resonance states
      overlapping with the target one increases the selectivity of the scheme applied,
      and leads to achieve a remarkably higher degree of control. Lifetime enhancements
      by factors up to 20 are obtained when this selectivity is applied. The underlying
      reasons for such strong enhancements are analyzed and explained in the light of
      the equations of the model applied. Application of this strategy to control and
      enhance the lifetime of a system in excited states is envisioned. 

PMID- 24116568
TI  - New analytical model for the ozone electronic ground state potential surface and
      accurate ab initio vibrational predictions at high energy range.
AB  - An accurate description of the complicated shape of the potential energy surface
      (PES) and that of the highly excited vibration states is of crucial importance
      for various unsolved issues in the spectroscopy and dynamics of ozone and remains
      a challenge for the theory. In this work a new analytical representation is
      proposed for the PES of the ground electronic state of the ozone molecule in the
      range covering the main potential well and the transition state towards the
      dissociation. This model accounts for particular features specific to the ozone
      PES for large variations of nuclear displacements along the minimum energy path.
      The impact of the shape of the PES near the transition state (existence of the
      "reef structure") on vibration energy levels was studied for the first time. The
      major purpose of this work was to provide accurate theoretical predictions for
      ozone vibrational band centres at the energy range near the dissociation
      threshold, which would be helpful for understanding the very complicated high
      resolution spectra and its analyses currently in progress. Extended ab initio
      electronic structure calculations were carried out enabling the determination of
      the parameters of a minimum energy path PES model resulting in a new set of
      theoretical vibrational levels of ozone. A comparison with recent high-resolution
      spectroscopic data on the vibrational levels gives the root-mean-square
      deviations below 1 cm(-1) for ozone band centres up to 90% of the dissociation
      energy. New ab initio vibrational predictions represent a significant improvement
      with respect to all previously available calculations. 

PMID- 24116569
TI  - Tetratic phase of Hertzian spheres: Monte Carlo simulation.
AB  - The nature of the melting transition of a bilayer comprising Hertzian spheres,
      confined between parallel walls, was investigated with the multicolour domain
      decomposition Monte Carlo simulation. It was confirmed that an ordered bilayer
      structure with a square lattice symmetry appeared parallel to the walls of
      confinement at a certain density and temperature. Bond-orientational order
      parameters of the system were studied numerically, and it has been suggested that
      this system obeys a two-stage melting transition with an intermediate phase
      called the tetratic phase. A snapshot of the spatial distribution of domains in
      which the bond-orientational order of the system exists shows a filamentary
      structure in the transition regime. 

PMID- 24116570
TI  - Fundamental measure density functional theory study of liquid-vapor interface of
      dipolar and quadrupolar fluids.
AB  - We have studied interfacial structure and properties of liquid-vapor interfaces
      of dipolar fluids and quadrupolar fluids, respectively, using the classical
      density functional theory (DFT). Towards this end, we employ the fundamental
      measure DFT for a reference hard-sphere (HS) part of free energy and the modified
      mean field approximation for the correlation function of dipolar or quadrupolar
      fluid. At low temperatures we find that both the liquid-vapor interfacial density
      profile and orientational order parameter profile exhibit weakly damped
      oscillatory decay into the bulk liquid. At high temperatures the decay of
      interfacial density and order parameter profiles is entirely monotonic. The
      scaled temperature tau = 1 - T/T(c) that separates the two qualitatively
      different interfacial structures is in the range 0.10-0.15. At a given
      (dimensionless) temperature, increasing the dipolar or quadrupolar moment
      enhances the density oscillations. Application of an electric field (normal to
      the interface) will damp the oscillations. Likewise, at the given temperature,
      increasing the strength of any multipolar moment also increases the surface
      tensions while increasing the strength of the applied electric field will reduce
      the surface tensions. The results are compared with those based on the local
      density approximations (LDA) for the reference HS part of free energy as well as
      with results of numerical experiments.

PMID- 24116571
TI  - Broadband dynamics in neat 4-methyl-3-heptanol and in mixtures with 2-ethyl-1
      hexanol.
AB  - The relatively small dielectric Debye-like process of the monohydroxy alcohol 4
      methyl-3-heptanol (4M3H) was found to depend slightly on the intramolecular
      conformation. Proton and deuteron nuclear magnetic resonance demonstrate that the
      hydroxyl dynamics and the overall molecular dynamics take place on similar time
      scales in contrast to the situation for the structural isomer 2-ethyl-1-hexanol
      (2E1H) [S. Schildmann et al., J. Chem. Phys. 135, 174511 (2011)]. This indicates
      a very weak decoupling of Debye-like and structural relaxation which was further
      probed using volume expansivity experiments. Shear viscosity as well as
      diffusometry measurements were performed and the data were analyzed in terms of
      the Debye-Stokes-Einstein equations. In mixtures of 4M3H with 2E1H the Debye-like
      process becomes much stronger and for 2E1H mole fraction of more than 25% the
      behavior of this alcohol is rapidly approached. This finding is interpreted to
      indicate that the ring-like supramolecular structures in 4M3H become
      energetically unfavorable when adding 2E1H, an alcohol that tends to form chain
      like molecular aggregates. The concentration dependence of the Kirkwood factor in
      these mixtures displays a high degree of similarity with experimental results on
      monohydroxy alcohols in which the pressure or the location of the OH group within
      the molecular structure is varied. 

PMID- 24116572
TI  - Secondary relaxations in a series of organic phosphate glasses revealed by
      dielectric spectroscopy.
AB  - Dielectric susceptibility spectra of six chemically similar organic phosphate
      glass formers are analyzed in order to elucidate the spectral evolution of a
      multitude of secondary (beta) relaxation processes dominating the dielectric loss
      below the glass transition temperature T(g). By doing the spectral analysis we
      forgo any data fitting procedure and apply a model independent scaling approach
      instead. This approach assumes a constant distribution of activation energies
      g(E) underlying a plurality of thermally activated processes, which determine the
      beta-relaxation. The scaling reveals temperature independent, asymmetric
      distributions g(E) for temperatures well below T(g). Simultaneously, the
      temperature dependence of the relaxation strength of the beta-processes
      Deltaepsilon(beta)(T) is yielded, being nearly constant well in the glassy state.
      Already somewhat below T(g) the spectral scaling fails and reveals an apparent
      increase of the mean activation energy, leading to a weaker temperature
      dependence of the mean relaxation times tau(beta)(T). In the same temperature
      regime Deltaepsilon(beta)(T) starts to increase drastically, i.e., the softening
      of the glass near T(g) is reflected directly in the loss of temperature
      independence of g(E) and Deltaepsilon(beta)(T). Comparing the different glasses
      made from phosphate molecules with increasing number of internal degrees of
      freedom we do not see systematic changes in the spectral evolution. In some cases
      even identical distributions g(E) are found.

PMID- 24116573
TI  - Quantum molecular dynamics simulations of the thermophysical properties of
      shocked liquid ammonia for pressures up to 1.3 TPa.
AB  - We investigate via quantum molecular-dynamics simulations the thermophysical
      properties of shocked liquid ammonia up to the pressure 1.3 TPa and temperature
      120,000 K. The principal Hugoniot is predicted from the wide-range equation of
      state, which agrees well with the available experimental measurements up to 64
      GPa. Our systematic study of the structural properties demonstrates that the
      liquid ammonia undergoes a gradual phase transition along the Hugoniot. At about
      4800 K, the system transforms into a metallic, complex mixture state consisting
      of NH3, N2, H2, N, and H. Furthermore, we discuss the implications for the
      interiors of Uranus and Neptune.

PMID- 24116574
TI  - Structural motifs of pre-nucleation clusters.
AB  - Structural motifs of pre-nucleation clusters prepared in single, optically
      levitated supersaturated aqueous aerosol microparticles containing CaBr2 as a
      model system are reported. Cluster formation is identified by means of X-ray
      absorption in the Br K-edge regime. The salt concentration beyond the saturation
      point is varied by controlling the humidity in the ambient atmosphere surrounding
      the 15-30 MUm microdroplets. This leads to the formation of metastable
      supersaturated liquid particles. Distinct spectral shifts in near-edge spectra as
      a function of salt concentration are observed, in which the energy position of
      the Br K-edge is red-shifted by up to 7.1 +/- 0.4 eV if the dilute solution is
      compared to the solid. The K-edge positions of supersaturated solutions are found
      between these limits. The changes in electronic structure are rationalized in
      terms of the formation of pre-nucleation clusters. This assumption is verified by
      spectral simulations using first-principle density functional theory and
      molecular dynamics calculations, in which structural motifs are considered,
      explaining the experimental results. These consist of solvated CaBr2 moieties,
      rather than building blocks forming calcium bromide hexahydrates, the crystal
      system that is formed by drying aqueous CaBr2 solutions. 

PMID- 24116575
TI  - Diffusivity and hydration of hydrazine in liquid and supercritical water through
      molecular dynamics simulations and split-flow pulse injection experiments.
AB  - The diffusion properties and hydration structure of hydrazine in an aqueous
      solution are investigated through molecular dynamics simulations and split-flow
      pulse injection experiments. The simulations are performed from ambient
      conditions along the liquid side of the liquid-vapor coexistence curve, up to the
      critical point, and in the supercritical region at temperatures of 673, 773, 873,
      and 973 K and at densities ranging from 0.1 to 0.8 g cm(-3). The spatial
      distributions functions for hydrated water are presented. At ambient conditions,
      hydrazine is hydrated by 24 water molecules with about 1.6 H-bonds being donated
      to each nitrogen atom. The hydration number decreases with temperature along the
      coexistence curve and is seen to increase with system density in the
      supercritical region. At low density supercritical conditions, hydrazine has no
      appreciable hydration structure and is surrounded by only 2 water molecules at
      873 K and 0.1 g cm(-3). The diffusion coefficients for hydrazine at subcritical
      state conditions are found to be in agreement with Stokes-Einstein and Wilke
      Chang predictions. The diffusion coefficients in the supercritical region are
      found to correlate more closely with the overall fit to the Dymond equation. 

PMID- 24116577
TI  - Disordering and grain boundaries of (Ni,Fe)Cr2O4 spinels from atomistic
      calculations.
AB  - A novel empirical potential has been developed to evaluate the thermodynamic
      stability of Ni(1-x)Fe(x)Cr2O4 spinels. The simulations confirm the hypothesis
      that the NiCr2O4-FeCr2O4 pseudo-binary has normal structure spinel up to 1000 K
      and stabilizes as a solid solution. However, the disordering energy (normal to
      inverse spinel) is found higher for FeCr2O4 than for NiCr2O4 spinel. The
      formation energies of tilt, twist, and random grain boundaries have been
      calculated in pure NiCr2O4 and FeCr2O4. The same behavior has been found for both
      spinels. Detail analysis of the grain boundaries structure shows that the cation
      coordination number is a key parameter for the stability of the grain boundaries.
      With this criterion, we evidenced that the structural and energetic differences
      are caused only by nickel and iron cations.

PMID- 24116576
TI  - A steady-state non-equilibrium molecular dynamics approach for the study of
      evaporation processes.
AB  - Two non-equilibrium methods (called bubble method and splitting method,
      respectively) have been developed and tested to study the steady state
      evaporation of a droplet surrounded by its vapor, where the evaporation
      continuously occurs at the vapor-liquid interface while the droplet size remains
      constant. In the bubble method, gas molecules are continuously reinserted into a
      free volume (represented by a bubble) located at the centre of mass of the
      droplet to keep the droplet size constant. In the splitting method, a molecule
      close to the centre of mass of the droplet is split into two: In this way, the
      droplet size is also maintained during the evaporation. By additional local
      thermostats confined to the area of insertion, the effect of frequent insertions
      on properties such as density and temperature can be limited to the immediate
      insertion area. Perturbations are not observed in other parts of the droplet. In
      the end, both the bubble method and the splitting method achieve steady-state
      droplet evaporation. Although these methods have been developed using an isolated
      droplet, we anticipate that they will find a wide range of applications in the
      study of the evaporation of isolated films and droplets or thin films on heated
      substrates or under confinement. They can in principle also be used to study the
      steady-state of other physical processes, such as the diffusion or permeation of
      gas molecules or ions in a pressure gradient or a concentration gradient. 

PMID- 24116578
TI  - Thermodynamics of extensive interfaces between rigid, apolar walls and water.
AB  - A simple set of equations is proposed to govern the relations between the
      thermodynamic potentials in rigid, apolar wall-water systems, which is found to
      be consistent with the data for two systems: alkane plate-SPC/E water [R. Zangi
      and B. J. Berne, J. Phys. Chem. B 112(29), 8634-8644 (2008)] and graphene plate
      TIP4P/Ew water [R. Zangi, J. Phys. Chem. B 115, 2303-2311 (2011)]. These data
      exhibit exact compensation of enthalpy and entropy for the water-water
      interactions. Surface tension of the free water surface is the invariant excess
      free energy per unit area for the water phase in these wall-water systems at
      thermodynamic equilibrium.

PMID- 24116579
TI  - Branching points in the low-temperature dipolar hard sphere fluid.
AB  - In this contribution, we investigate the low-temperature, low-density behaviour
      of dipolar hard-sphere (DHS) particles, i.e., hard spheres with dipoles embedded
      in their centre. We aim at describing the DHS fluid in terms of a network of
      chains and rings (the fundamental clusters) held together by branching points
      (defects) of different nature. We first introduce a systematic way of classifying
      inter-cluster connections according to their topology, and then employ this
      classification to analyse the geometric and thermodynamic properties of each
      class of defects, as extracted from state-of-the-art equilibrium Monte Carlo
      simulations. By computing the average density and energetic cost of each defect
      class, we find that the relevant contribution to inter-cluster interactions is
      indeed provided by (rare) three-way junctions and by four-way junctions arising
      from parallel or anti-parallel locally linear aggregates. All other (numerous)
      defects are either intra-cluster or associated to low cluster-cluster interaction
      energies, suggesting that these defects do not play a significant part in the
      thermodynamic description of the self-assembly processes of dipolar hard spheres.

PMID- 24116580
TI  - Molecular field theory for biaxial smectic A liquid crystals.
AB  - Thermotropic biaxial nematic phases seem to be rare, but biaxial smectic A phases
      less so. Here we use molecular field theory to study a simple two-parameter
      model, with one parameter promoting a biaxial phase and the second promoting
      smecticity. The theory combines the biaxial Maier-Saupe and McMillan models. We
      use alternatively the Sonnet-Virga-Durand (SVD) and geometric mean approximations
      (GMA) to characterize molecular biaxiality by a single parameter. For non-zero
      smecticity and biaxiality, the model always predicts a ground state biaxial
      smectic A phase. For a low degree of smectic order, the phase diagram is very
      rich, predicting uniaxial and biaxial nematic and smectic phases, with the
      addition of a variety of tricritical and tetracritical points. For higher degrees
      of smecticity, the region of stability of the biaxial nematic phase is restricted
      and eventually disappears, yielding to the biaxial smectic phase. Phase diagrams
      from the two alternative approximations for molecular biaxiality are similar,
      except inasmuch that SVD allows for a first-order isotropic-biaxial nematic
      transition, whereas GMA predicts a Landau point separating isotropic and biaxial
      nematic phases. We speculate that the rarity of thermotropic biaxial nematic
      phases is partly a consequence of the presence of stabler analogous smectic
      phases. 

PMID- 24116581
TI  - Polymerization-induced spinodal decomposition of ethylene glycol/phenolic resin
      solutions under electric fields.
AB  - Temporal evolution of polymerization-induced spinodal decomposition (PISD) under
      electric fields was investigated numerically in ethylene glycol/phenolic resin
      solutions with different initial composition. A model composed of the nonlinear
      Cahn-Hilliard-Cook equation for spinodal decomposition and a rate equation for
      curing reaction was utilized to describe the PISD phenomenon. As initial
      composition varied, deformed droplet-like and aligned bi-continuous structures
      were observed in the presence of an electric field. Moreover, the anisotropic
      parameter (D), determined from the 2D-FFT power spectrum, was employed to
      quantitatively characterize the degree of morphology anisotropy. The value of D
      increased quickly in the early stage and then decreased in the intermediate stage
      of spinodal decomposition, which was attributed to the resistance of coarsening
      process to morphology deformation and the decline of electric stress caused by
      polymerization reaction. The results can also provide a guidance on how to
      control the morphology of monolithic porous polymer and carbon materials with
      anisotropic structures. 

PMID- 24116582
TI  - Phase field method for nonequilibrium dynamics of reversible self-assembly
      systems.
AB  - Phase field methods are extended to describe the nonequilibrium dynamics of
      reversible self-assembly systems, an extension that is complicated by the mutual
      coupling of many non-conserved order parameters into a set of highly nonlinear
      partial differential equations. Further complications arise because the sum of
      all non-conserved order parameters equals a conserved order parameter. The theory
      is developed for the simplest model of reversible self-assembly in which no
      additional constraints are imposed on the self-assembly process since the
      extension to treat more complex self-assembly models is straightforward. Specific
      calculations focus on the time evolution of the cluster size distribution for a
      free association system that is rapidly dropped from one ordered state to a more
      ordered state within the one-phase region. The dynamics proceed as expected,
      thereby providing validation of the theory which is also capable of treating
      systems with spatial inhomogeneities. 

PMID- 24116583
TI  - Effect of binding to carbon black on the dynamics of 1,4-polybutadiene.
AB  - The nature of the interactions of polymers at the surface of nanoparticles is
      crucial to understanding the dynamics and their relation to mechanical
      properties. The effect of binding (both chemical attachment and physical
      adsorption) on the local and global dynamics of chain molecules remains a
      controversial subject. Using neutron scattering and dynamic mechanical
      spectroscopies, we measured the slow conformational and terminal relaxations, as
      well as the fast local dynamics, of 1,4-polybutadiene (PBD) containing carbon
      black (CB) particles. We observed a substantial decrease in the flexibility of
      bound segments at temperatures through the glass transition temperature, T(g).
      The longer range motions of the PBD become more suppressed and cooperative as
      temperature decreases, while the relaxation time of the fast local dynamics is
      little affected by the CB particles. The mobile fraction of PBD is less sensitive
      to temperature when bound. Mechanical spectroscopy indicates that both the local
      segmental dynamics and the global chain modes are slowed by the filler. These
      results are consistent with transient structural arrest of the slow dynamics of
      atoms adjacent to the particles.

PMID- 24116584
TI  - One-dimensional potential of mean force underestimates activation barrier for
      transport across flexible lipid membranes.
AB  - Transport of a fullerene-like nanoparticle across a lipid bilayer is investigated
      by coarse-grained molecular dynamics (MD) simulations. Potentials of mean force
      (PMF) acting on the nanoparticle in a flexible bilayer suspended in water and a
      bilayer restrained to a flat surface are computed by constrained MD simulations.
      The rate of the nanoparticle transport into the bilayer interior is predicted
      using one-dimensional Langevin models based on these PMFs. The predictions are
      compared with the transport rates obtained from a series of direct
      (unconstrained) MD simulations of the solute transport into the flexible bilayer.
      It is observed that the PMF acting on the solute in the flexible membrane
      underestimates the transport rate by more than an order of magnitude while the
      PMF acting on the solute in the restrained membrane yields an accurate estimate
      of the activation energy for transport into the flexible membrane. This paradox
      is explained by a coexistence of metastable membrane configurations for a range
      of the solute positions inside and near the flexible membrane. This leads to a
      significant reduction of the contribution of the transition state to the mean
      force acting on the solute. Restraining the membrane shape ensures that there is
      only one stable membrane configuration corresponding to each solute position and
      thus the transition state is adequately represented in the PMF. This mechanism is
      quite general and thus this phenomenon is expected to occur in a wide range of
      interfacial systems. A simple model for the free energy landscape of the coupled
      solute-membrane system is proposed and validated. This model explicitly accounts
      for effects of the membrane deformations on the solute transport and yields an
      accurate prediction of the activation energy for the solute transport. 

PMID- 24116585
TI  - Dynamics of edge dislocations in a sheared lamellar mesophase.
AB  - The dynamics and interactions of edge dislocations in a nearly aligned sheared
      lamellar mesophase is analysed to provide insights into the relationship between
      disorder and rheology. First, the mesoscale permeation and momentum equations for
      the displacement field in the presence of external forces are derived from the
      model H equations for the concentration and momentum field. The secondary flow
      generated due to the mean shear around an isolated defect is calculated, and the
      excess viscosity due to the presence of the defect is determined from the excess
      energy dissipation due to the secondary flow. The excess viscosity for an
      isolated defect is found to increase with system size in the cross-stream
      direction as L(3/2) for an isolated defect, though this divergence is cut-off due
      to interactions in a defect suspension. As the defects are sheared past each
      other due to the mean flow, the Peach-Koehler force due to elastic interaction
      between pairs of defects is found to cause no net displacement relative to each
      other as they approach from large separation to the distance of closest approach.
      The equivalent force due to viscous interactions is found to increase the
      separation for defects of opposite sign, and decrease the separation for defects
      of same sign. During defect interactions, we find that there is no buckling
      instability due to dilation of layers for systems of realistic size. However,
      there is another mechanism, which is the velocity difference generated across a
      slightly deformed bilayer due to the mean shear, which could result in the
      creation of new defects.

PMID- 24116586
TI  - Zigzag transitions and nonequilibrium pattern formation in colloidal chains.
AB  - Paramagnetic colloidal particles that are optically trapped in a linear array can
      form a zigzag pattern when an external magnetic field induces repulsive
      interparticle interactions. When the traps are abruptly turned off, the particles
      form a nonequilibrium expanding pattern with a zigzag symmetry, even when the
      strength of the magnetic interaction is weaker than that required to break the
      linear symmetry of the equilibrium state. We show that the transition to the
      equilibrium zigzag state is always potentially possible for purely harmonic
      traps. For anharmonic traps that have a finite height, the equilibrium zigzag
      state becomes unstable above a critical anharmonicity. A normal mode analysis of
      the equilibrium line configuration demonstrates that increasing the magnetic
      field leads to a hardening and softening of the spring constants in the
      longitudinal and transverse directions, respectively. The mode that first becomes
      unstable is the mode with the zigzag symmetry, which explains the symmetry of
      nonequilibrium patterns. Our analytically tractable models help to give further
      insight into the way that the interplay of factors such as the length of the
      chain, hydrodynamic interactions, thermal fluctuations affects the formation and
      evolution of the experimentally observed nonequilibrium patterns. 

PMID- 24116587
TI  - Size and boundary effects on the diffusive behavior of elongated colloidal
      particles in a strongly confined dense dispersion.
AB  - In very recent experimental work, diffusive motion of individual particles in a
      dense columnar phase of colloidal suspension of filamentous virus particles
      probed by means of fluorescence video microscopy [S. Naderi, E. Pouget, P.
      Ballesta, P. van der Schoot, M. P. Lettinga, and E. Grelet, Phys. Rev. Lett. 111,
      037801 (2013)]. Rare events were observed in which the minority fluorescently
      labeled particles engage in sudden, jump-like motion along the director. The jump
      length distribution turned out to be biased towards a half and a full particle
      length. We suggest these events may be indicative of two types of particle
      motion, one in which particles overtake other particles in the same column and
      the other where a column re-equilibrates after a particle leaves a column either
      to enter into another column or into a void defect on the lattice. Our Brownian
      dynamics simulations of a quasi one-dimensional system of semi-flexible
      particles, subject to a Gaussian confinement potentials mimicking the effects of
      the self-consistent molecular field in the columnar phase, support this idea. We
      find that the frequency of overtaking depends on the linear fraction of particles
      and the steepness of the confining potential. The re-equilibration time of a
      column after a particle is removed from it is much shorter than the self
      diffusion timescale. For the case of large system sizes and periodic boundary
      conditions, overtaking events do not present themselves as full-length jumps.
      Only if the boundary conditions are reflecting and the system is sufficiently
      small, full length jumps are observed in particle trajectories. The reason is
      that only then the amplitude of the background fluctuations is smaller than a
      particle length. Increasing the bending flexibility of the particles on the one
      hand enhances the ability of particles to overtake each other but on the other it
      enhances fluctuations that wash out full jumps in particle trajectories. 

PMID- 24116588
TI  - Numerical evidences for a free energy barrier in starlike polymer brushes.
AB  - The existence of a free energy barrier, which prohibits the upward motion of
      retracted molecules into the surface region of starlike polymer brushes, is
      analyzed through molecular dynamics simulations in good solvent. This barrier
      emerges at moderate and high grafting densities, as a result of a density
      discontinuity at the branching points of the highly stretched starlike molecules.
      The vertical force profiles of brushes of varying densities are taken with the
      help of a probe-particle that is gradually moved into the brush, and the results
      are compared with the density profiles and their negative gradients which
      generate the local osmotic pressures. Chain expulsion simulations, supported by
      scaling theory, are conducted to understand the dynamics of individual molecules
      inside the brushes. We prove that the flip-rates between retracted and extended
      states, being of relevance for the generation of efficiently switchable,
      environment-responsive brush layers, are determined by the elastic tension of the
      stretched molecules. 

PMID- 24116589
TI  - Optimization of collective enzyme activity via spatial localization.
AB  - The spatial organization of enzymes often plays a crucial role in the
      functionality and efficiency of enzymatic pathways. To fully understand the
      design and operation of enzymatic pathways, it is therefore crucial to understand
      how the relative arrangement of enzymes affects pathway function. Here we
      investigate the effect of enzyme localization on the flux of a minimal two-enzyme
      pathway within a reaction-diffusion model. We consider different reaction
      kinetics, spatial dimensions, and loss mechanisms for intermediate substrate
      molecules. Our systematic analysis of the different regimes of this model reveals
      both universal features and distinct characteristics in the phenomenology of
      these different systems. In particular, the distribution of the second pathway
      enzyme that maximizes the reaction flux undergoes a generic transition from co
      localization with the first enzyme when the catalytic efficiency of the second
      enzyme is low, to an extended profile when the catalytic efficiency is high.
      However, the critical transition point and the shape of the extended optimal
      profile is significantly affected by specific features of the model. We explain
      the behavior of these different systems in terms of the underlying stochastic
      reaction and diffusion processes of single substrate molecules. 

PMID- 24116590
TI  - Comment on "Temperature divergence of the dynamics of a poly(vinyl acetate)
      glass: dielectric vs. mechanical behaviors" [J. Chem. Phys. 136, 154901 (2012)].

PMID- 24116591
TI  - Response to "Comment on 'Temperature divergence of the dynamics of a poly(vinyl
      acetate) glass: dielectric vs. mechanical behaviors'" [J. Chem. Phys. 139, 137101
      (2013)].

PMID- 24116594
TI  - Communication: Nonexistence of a critical point within the Kirkwood superposition
      approximation.
AB  - An analytic argument is given to show that the application of the Kirkwood
      superposition approximation to the description of fluid correlation functions
      precludes the existence of a critical point. The argument holds irrespective of
      the dimension of the system and the specific form of the interaction potential
      and settles a long-standing controversy surrounding the nature of the critical
      behavior predicted within the approximation. 

PMID- 24116595
TI  - Communication: Phase behavior of materials with isotropic interactions designed
      by inverse strategies to favor diamond and simple cubic lattice ground states.
AB  - We use molecular simulation to construct equilibrium phase diagrams for two
      recently introduced model materials with isotropic, soft-repulsive pair
      interactions designed to favor diamond and simple cubic lattice ground states,
      respectively, over a wide range of densities [Jain et al., Soft Matter 9, 3866
      (2013)]. We employ free energy based Monte Carlo simulation techniques to
      precisely trace the inter-crystal and fluid-crystal coexistence curves. We find
      that both model materials display rich polymorphic phase behavior featuring
      stable crystals corresponding to the target ground-state structures, as well as a
      variety of other crystalline (e.g., hexagonal and body-centered cubic) phases and
      multiple reentrant melting transitions. 

PMID- 24116596
TI  - Communication: Ultraviolet photodissociation dynamics of the simplest Criegee
      intermediate CH2OO.
AB  - The velocity and angular distributions of O (1)D photofragments arising from UV
      excitation of the CH2OO intermediate on the B (1)A' <- X (1)A' transition are
      characterized using velocity map ion imaging. The anisotropic angular
      distribution yields the orientation of the transition dipole moment, which
      reflects the pi* <- pi character of the electronic transition associated with the
      COO group. The total kinetic energy release distributions obtained at several
      photolysis wavelengths provide detail on the internal energy distribution of the
      formaldehyde cofragments and the dissociation energy of CH2OO X (1)A' to O (1)D +
      H2CO X (1)A1. A common termination of the total kinetic energy distributions,
      after accounting for the different excitation energies, gives an upper limit for
      the CH2OO X (1)A' dissociation energy of D0 <= 54 kcal mol(-1), which is compared
      with theoretical predictions including high level multi-reference ab initio
      calculations. 

PMID- 24116597
TI  - The chemical bond in external electric fields: energies, geometries, and
      vibrational Stark shifts of diatomic molecules.
AB  - It is shown that the response of molecular properties of diatomics such as the
      total energy, the bond length, and the vibrational Stark shift to an external
      homogenous electric field (EF) can be predicted from field-free observable
      properties such as the equilibrium bond length, the bond dissociation energy, the
      polarizability and dipole moment functions, and the vibrational frequency. Delley
      [J. Mol. Struct.: THEOCHEM 434, 229 (1998)] suggested to approximate the
      potential energy surface under an EF by a Morse function augmented with a EF term
      proportional to the internuclear separation. In this work, this term is replaced
      by the expression of the field-induced energy change which yields a field
      perturbed Morse potential that tends to a constant asymptotic limit when the EF
      term itself become proportional to the sum of the polarizabilities of the
      separated atoms. The model is validated by comparison with direct calculations on
      nine diatomics, five homo-nuclear (H2, N2, O2, F2, and Cl2) and four hetero
      nuclear (HF, HCl, CO, and NO), covering a range and combinations of dipole
      moments and polarizabilities. Calculations were conducted at the quadratic
      configuration interaction with single and double excitations (QCISD) and density
      functional theory (DFT)-B3LYP levels of theory using the 6-311++G(3df,2pd) basis
      set. All results agree closely at the two levels of theory except for the Stark
      effect of NO which is not correctly predicted by QCISD calculations as further
      calculations, including at the coupled cluster with single and double excitation
      (CCSD) level of theory, demonstrate. 

PMID- 24116598
TI  - Monte Carlo methods for estimating depletion potentials in highly size
      asymmetrical hard sphere mixtures.
AB  - We investigate Monte Carlo simulation strategies for determining the effective
      ("depletion") potential between a pair of hard spheres immersed in a dense sea of
      much smaller hard spheres. Two routes to the depletion potential are considered.
      The first is based on estimates of the insertion probability of one big sphere in
      the presence of the other; we describe and compare three such methods. The second
      route exploits collective (cluster) updating to sample the depletion potential as
      a function of the separation of the big particles; we describe two such methods.
      For both routes, we find that the sampling efficiency at high densities of small
      particles can be enhanced considerably by exploiting "geometrical shortcuts" that
      focus the computational effort on a subset of small particles. All the methods we
      describe are readily extendable to particles interacting via arbitrary
      potentials. 

PMID- 24116599
TI  - Boundary based on exchange symmetry theory for multilevel simulations. II.
      Multiple time scale approach.
AB  - The QM/MM BEST method presented in the first article of this series [M. Shiga and
      M. Masia, J. Chem. Phys. 139, 044120 (2013)] has been applied herein to simulate
      the whole series of hydrated alkali ions. In this article we show how to overcome
      the sampling bottleneck for QM/MM simulations by using our method with multiple
      time scale algorithm (MTS-BEST). We extend the use of MTS-BEST to ab initio QM/MM
      path integral molecular dynamics simulations, thus demonstrating that one could
      obtain a complete quantum description of the primary subsystem based on first
      principles. We highlight that the MTS-BEST approach could be generally applied to
      hybrid multiscale simulation of diffusive systems, thus extending its relevance
      to a broad class of simulation techniques beyond QM/MM. We show that it is
      important to account for electron correlation to better reproduce the hydration
      structural properties such as the ion-water radial distribution functions, and
      the anisotropic angular distributions around the ion. 

PMID- 24116600
TI  - On the effects of permanent molecular dipoles in the simultaneous absorption of
      two photons: full generalized rotating wave approximation versus analytical
      results.
AB  - The effects of permanent dipoles, and the relative effects of the direct
      permanent dipole and the virtual state excitation mechanisms, are discussed for
      excitations involving the simultaneous absorption of two identical photons. Two
      molecular models for two-photon excitation, one dominated by the direct permanent
      dipole mechanism and the other having significant contributions from both
      excitation mechanisms, are used for this purpose. Resonance profiles, as a
      function of laser intensity, are evaluated for both models by employing the full
      Generalized Rotating Wave Approximation method and the recently developed
      Analytic Generalized Rotating Wave Approximation (AGRWA). The profiles are used
      to assess (1) the nature of the effects of permanent molecular dipoles, (2) the
      relative contributions of the two excitation mechanisms, and (3) the validity of
      the AGRWA for two-photon excitations. The AGRWA is a very useful
      interpretive/predictive tool even for higher laser intensities where its validity
      becomes questionable. It can be used to suggest how to exploit the effects of
      molecular permanent dipoles to enhance two photon excitations using both
      excitation mechanisms. 

PMID- 24116601
TI  - Enhanced conformational sampling using enveloping distribution sampling.
AB  - To lessen the problem of insufficient conformational sampling in biomolecular
      simulations is still a major challenge in computational biochemistry. In this
      article, an application of the method of enveloping distribution sampling (EDS)
      is proposed that addresses this challenge and its sampling efficiency is
      demonstrated in simulations of a hexa-beta-peptide whose conformational
      equilibrium encompasses two different helical folds, i.e., a right-handed
      2.7(10/12)-helix and a left-handed 3(14)-helix, separated by a high energy
      barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force
      field did not reach convergence of the free enthalpy difference between the two
      helices even after 500 ns of simulation time. The use of soft-core non-bonded
      interactions in the centre of the peptide did enhance the number of transitions
      between the helices, but at the same time led to neglect of relevant helical
      configurations. In the simulations of a two-state EDS reference Hamiltonian that
      envelops both the physical peptide and the soft-core peptide, sampling of the
      conformational space of the physical peptide ensures that physically relevant
      conformations can be visited, and sampling of the conformational space of the
      soft-core peptide helps to enhance the transitions between the two helices. The
      EDS simulations sampled many more transitions between the two helices and showed
      much faster convergence of the relative free enthalpy of the two helices compared
      with the standard MD simulations with only a slightly larger computational effort
      to determine optimized EDS parameters. Combined with various methods to smoothen
      the potential energy surface, the proposed EDS application will be a powerful
      technique to enhance the sampling efficiency in biomolecular simulations.

PMID- 24116602
TI  - Mechanisms and topology determination of complex chemical and biological network
      systems from first-passage theoretical approach.
AB  - The majority of chemical and biological processes can be viewed as complex
      networks of states connected by dynamic transitions. It is fundamentally
      important to determine the structure of these networks in order to fully
      understand the mechanisms of underlying processes. A new theoretical method of
      obtaining topologies and dynamic properties of complex networks, which utilizes a
      first-passage analysis, is developed. Our approach is based on a hypothesis that
      full temporal distributions of events between two arbitrary states contain full
      information on number of intermediate states, pathways, and transitions that lie
      between initial and final states. Several types of network systems are analyzed
      analytically and numerically. It is found that the approach is successful in
      determining structural and dynamic properties, providing a direct way of getting
      topology and mechanisms of general chemical network systems. The application of
      the method is illustrated on two examples of experimental studies of motor
      protein systems. 

PMID- 24116603
TI  - Total molecular photoionization cross-sections by algebraic diagrammatic
      construction-Stieltjes-Lanczos method: benchmark calculations.
AB  - In [K. Gokhberg, V. Vysotskiy, L. S. Cederbaum, L. Storchi, F. Tarantelli, and V.
      Averbukh, J. Chem. Phys. 130, 064104 (2009)] we introduced a new L(2) ab initio
      method for the calculation of total molecular photoionization cross-sections. The
      method is based on the ab initio description of discretized photoionized
      molecular states within the many-electron Green's function approach, known as
      algebraic diagrammatic construction (ADC), and on the application of Stieltjes
      Chebyshev moment theory to Lanczos pseudospectra of the ADC electronic
      Hamiltonian. Here we establish the accuracy of the new technique by comparing the
      ADC-Lanczos-Stieltjes cross-sections in the valence ionization region to the
      experimental ones for a series of eight molecules of first row elements: HF, NH3,
      H2O, CO2, H2CO, CH4, C2H2, and C2H4. We find that the use of the second-order ADC
      technique [ADC(2)] that includes double electronic excitations leads to a
      substantial systematic improvement over the first-order method [ADC(1)] and to a
      good agreement with experiment for photon energies below 80 eV. The use of
      extended second-order ADC theory [ADC(2)x] leads to a smaller further
      improvement. Above 80 eV photon energy all three methods lead to significant
      deviations from the experimental values which we attribute to the use of Gaussian
      single-electron bases. Our calculations show that the ADC(2)-Lanczos-Stieltjes
      technique is a reliable and efficient ab initio tool for theoretical prediction
      of total molecular photo-ionization cross-sections in the valence region.

PMID- 24116604
TI  - Nonlinear biochemical signal processing via noise propagation.
AB  - Single-cell studies often show significant phenotypic variability due to the
      stochastic nature of intra-cellular biochemical reactions. When the numbers of
      molecules, e.g., transcription factors and regulatory enzymes, are in low
      abundance, fluctuations in biochemical activities become significant and such
      "noise" can propagate through regulatory cascades in terms of biochemical
      reaction networks. Here we develop an intuitive, yet fully quantitative method
      for analyzing how noise affects cellular phenotypes based on identifying a
      system's nonlinearities and noise propagations. We observe that such noise can
      simultaneously enhance sensitivities in one behavioral region while reducing
      sensitivities in another. Employing this novel phenomenon we designed three
      biochemical signal processing modules: (a) A gene regulatory network that acts as
      a concentration detector with both enhanced amplitude and sensitivity. (b) A non
      cooperative positive feedback system, with a graded dose-response in the
      deterministic case, that serves as a bistable switch due to noise-induced ultra
      sensitivity. (c) A noise-induced linear amplifier for gene regulation that
      requires no feedback. The methods developed in the present work allow one to
      understand and engineer nonlinear biochemical signal processors based on
      fluctuation-induced phenotypes. 

PMID- 24116605
TI  - A periodic charge-dipole electrostatic model. II. A kinetic-exchange-correlation
      correction.
AB  - We extend the periodic charge-dipole electrostatic model, see I. V. Bodrenko, M.
      Sierka, E. Fabiano, and F. Della Sala, J. Chem. Phys. 137, 134702 (2012), to
      include a kinetic-exchange-correlation (KXC) correction. The KXC correction is
      approximated by means of an extended-Huckel-type formula, it is exact in the
      infinite jellium model and it is also computationally efficient as it requires
      only the computation of overlap integrals. Tests on the linear response of silver
      slabs to an external electrostatic perturbation show that the KXC correction
      yields a very accurate description of induced dipole and of the whole induced
      charge density profile. We also show that the KXC parameters are quite
      transferable and related to the atomic polarizability. 

PMID- 24116606
TI  - Local hyperdynamics.
AB  - We present a new formulation of the hyperdynamics method in which the biasing
      effect is local, making it suitable for large systems. In standard hyperdynamics,
      the requirement that the bias potential be zero everywhere on the dividing
      surface bounding the state has the consequence that as the system size increases
      the boost factor decays to unity, regardless of the form of the bias potential.
      In the new method, the bias force on each atom is obtained by differentiating a
      local bias energy that depends only on the coordinates of atoms within a finite
      range of this atom. This bias force is thus independent of the bias force in
      distant parts of the system, providing a method that gives a constant boost
      factor, independent of the system size. We demonstrate for some realistic
      atomistic systems that the method gives escape rates in excellent agreement with
      direct molecular dynamics simulations. 

PMID- 24116607
TI  - Collective effects due to dipolar fields as the origin of the extremely random
      behavior in hyperpolarized NMR maser: a theoretical and numerical study.
AB  - Numerical simulations based on microscopic approach are used to explore the spin
      dynamics encountered in the recently reported hyperpolarized (129)Xe NMR maser
      [D. J. Y. Marion, G. Huber, P. Berthault, and H. Desvaux, ChemPhysChem 9, 1395
      1401 (2008)] where series of amplitude modulated rf emissions are observed. The
      integration of the dynamic features of the electronic detection circuit in the
      present simulations, based on non-linear Maxwell-Bloch differential equations
      with dipole-dipole interactions, allows us to prove that the experimentally
      observed extremely random amplitude modulations crucially require the long
      distance dipolar couplings between the nuclear spins with the feedback field
      acting as an amplifier. The massive dipolar couplings act, when the magnetization
      is largely tilted off the longitudinal axis, as an apparent transverse self
      relaxation mechanism which destroys coherence. This, in particular, explains why
      the final magnetization after emissions can still be opposite to the magnetic
      field direction, i.e., being in an unstable state. 

PMID- 24116608
TI  - Exploring control landscapes for laser-driven molecular fragmentation.
AB  - The growing success of quantum optimal control experiments has been attributed to
      the favorable topology of the control landscape, which specifies the functional
      relationship between the physical objective and the control variables describing
      the applied field. This work explores experimental control landscapes expressing
      the yields of dissociative ionization products from halogenated hydrocarbons in
      terms of three control variables specifying a polynomial expansion of the
      spectral phase of the ultrafast laser pulse. Many of the landscapes in this work
      exhibit features predicted by control landscape theory, including a lack of
      suboptimal extrema, i.e., "traps" and the presence of connected optimal level
      sets, i.e., continuously varying values of the control variables that produce an
      optimal objective yield. Placing significant constraints on the control
      resources, particularly by limiting the laser pulse energy, was found to distort
      the underlying landscape topology. The control landscapes from a diverse, yet
      related family of halogenated hydrocarbons are shown to possess similar features,
      reflecting the chemical similarity of the compounds. 

PMID- 24116609
TI  - Ultrafast desorption of molecular ions by XUV-photons, passing through dielectric
      hollow tip.
AB  - Pulsed desorption of organic conducting polymer by XUV-photons, formed by a thin
      capillary collimator, has been investigated. Short-wavelength radiation has been
      resulted from a metal target irradiated by a sharply focused Ti:Sa laser beam
      (0.8 MUm, 40 fs, 3 mJ/pulse) and has been filtered by Mylar-gold substrate.
      Single shot and 1-kHz pulses regimes of driving femtosecond laser have been
      compared using a time-of-flight mass spectrometer. A stepwise function of
      photoion signal vs laser pulse energy has been observed. 

PMID- 24116610
TI  - Nuclear magnetic relaxation induced by exchange-mediated orientational
      randomization: longitudinal relaxation dispersion for a dipole-coupled spin-1/2
      pair.
AB  - In complex biological or colloidal samples, magnetic relaxation dispersion (MRD)
      experiments using the field-cycling technique can characterize molecular motions
      on time scales ranging from nanoseconds to microseconds, provided that a rigorous
      theory of nuclear spin relaxation is available. In gels, cross-linked proteins,
      and biological tissues, where an immobilized macromolecular component coexists
      with a mobile solvent phase, nuclear spins residing in solvent (or cosolvent)
      species relax predominantly via exchange-mediated orientational randomization
      (EMOR) of anisotropic nuclear (electric quadrupole or magnetic dipole) couplings.
      The physical or chemical exchange processes that dominate the MRD typically occur
      on a time scale of microseconds or longer, where the conventional perturbation
      theory of spin relaxation breaks down. There is thus a need for a more general
      relaxation theory. Such a theory, based on the stochastic Liouville equation
      (SLE) for the EMOR mechanism, is available for a single quadrupolar spin I = 1.
      Here, we present the corresponding theory for a dipole-coupled spin-1/2 pair. To
      our knowledge, this is the first treatment of dipolar MRD outside the motional
      narrowing regime. Based on an analytical solution of the spatial part of the SLE,
      we show how the integral longitudinal relaxation rate can be computed
      efficiently. Both like and unlike spins, with selective or non-selective
      excitation, are treated. For the experimentally important dilute regime, where
      only a small fraction of the spin pairs are immobilized, we obtain simple
      analytical expressions for the auto-relaxation and cross-relaxation rates which
      generalize the well-known Solomon equations. These generalized results will be
      useful in biophysical studies, e.g., of intermittent protein dynamics. In
      addition, they represent a first step towards a rigorous theory of water (1)H
      relaxation in biological tissues, which is a prerequisite for unravelling the
      molecular basis of soft-tissue contrast in clinical magnetic resonance imaging. 

PMID- 24116611
TI  - Two-dimensional RF pulses: a new approach to selectively exciting J-coupled spins
      in nuclear magnetic resonance.
AB  - A new scheme for the excitation of spins according to the joint values of their
      heteronuclear or homonuclear J couplings and of their chemical shifts, is
      proposed and demonstrated. The principles of the new pulses involved derive from
      those employed in NMR imaging for exciting arbitrary 2D spatial shapes, using so
      called "multidimensional" RF pulses. It is shown that if recast in a suitable
      spectroscopic framework, the distinction that pi-pulses enable to establish
      between linear and bilinear interactions, support the selective excitation of
      coherences possessing arbitrary combinations of chemical shift and J-coupling
      values--a flexibility akin to that provided by a 2D J-resolved NMR spectrum.
      Details on the execution of the resulting 2D "J-shift" RF pulses are given, and
      examples where excitation only addresses spins with particular chemical shift
      offsets fulfilling specific J-coupling displacements, are demonstrated.
      Additional instances where such pulses could be applied, as well as main
      limitations of this new approach, are briefly discussed.

PMID- 24116612
TI  - Fully absorptive 3D IR spectroscopy using a dual mid-infrared pulse shaper.
AB  - This paper presents the implementation of 3D IR spectroscopy by adding a second
      pump beam to a two-beam 2D IR spectrometer. An independent mid-IR pulse shaper is
      used for each pump beam, which can be programmed to collect its corresponding
      dimension in either the frequency or time-domains. Due to the phase matching
      geometry employed here, absorptive 3D IR spectra are automatically obtained,
      since all four of the rephasing and non-rephasing signals necessary to generate
      absorptive spectra are collected simultaneously. Phase cycling is used to isolate
      the fifth-order from the third-order signals. The method is demonstrated on
      tungsten hexacarbonyl (W(CO)6) and dicarbonylacetylacetonato rhodium (I), for
      which the eigenstates are extracted up to the third excited state. Pulse shaping
      affords a high degree of control over 3D IR experiments by making possible mixed
      time- and frequency-domain experiments, fast data acquisition and straightforward
      implementation. 

PMID- 24116613
TI  - High resolution spectral analysis of oxygen. III. Laboratory investigation of the
      airglow bands.
AB  - We report the first high spectral resolution laboratory measurements of simulated
      oxygen A-band night glow. Our static discharge system approximates the conditions
      of the mesospheric oxygen night glow--suggesting O((1)D) + O2 (X(3)Sigmag(-)) ->
      O((3)P) + O2 (b(1)Sigmag(+)) -> O2 (X(3)Sigmag(-)) + hnu as the primary source of
      the emission. Additionally, use of the static cell has enabled us to collect
      spectra for all six molecular oxygen isotopologues using isotopically enriched
      samples. The (0,0), (0,1), and (1,1) b - X vibrational bands were observed for
      all six isotopologues. The (1,2) and (2,2) bands were also observed for (16)O2.
      The frequencies of the observed (0,1) transitions resolved discrepancies in Raman
      data for (16)O(17)O, (17)O2, and (17)O(18)O, enabling us to improve the
      vibrational parameterization of the ground electronic state global fit.
      Rotationally resolved intensities were determined for the (0,0), (0,1), and (1,1)
      bands. The experimental band intensity ratios I(0,0)/I(0,1) = 13.53(24);
      I(1,1)/I(1,0) = 11.9(65); I(0,0)/I(0,2) = 503(197); and I(1,1)/I(1,2) = 5.6(19)
      are in excellent agreement with the recent mesospheric remote sensing data and
      calculated Franck-Condon factors.

PMID- 24116614
TI  - Temperature dependences for the reactions of O2(-) and O(-) with N and O atoms in
      a selected-ion flow tube instrument.
AB  - Rate constants for the reactions of O2(-) and O(-) with N and O atoms have been
      measured for the first time as a function of temperature from 173 to 500 K for O(
      ) reactions and 173 to 400 K for O2(-) reactions. Room temperature rate constants
      for O2(-) reacting with N and O are 3.1 * 10(-10) and 1.7 * 10(-10) cm(3) s(-1),
      respectively, and the corresponding O(-) rate constants are 1.7 * 10(-10) and 1.5
      * 10(-10) cm(3) s(-1), in good agreement with previous values. Temperature
      dependences are about T(-1.7) for both O2(-) reactions and T(-0.6) and T(-1.3)
      for the reactions of O(-) with N and O, respectively. Branching for the O2(-)
      reaction with N is found to predominantly form O(-) (>85%) in contrast to
      previous measurements, which reported NO2 + e(-) as the main channel.
      Calculations point to the present results being correct. The potential energy
      surface for this reaction was calculated using density functional theory, coupled
      cluster with singles, doubles (triples), complete active space self-consistent
      field, and complete active space second-order perturbation methods and is found
      to be quite complex, with agreement between the calculated surface and the
      observed kinetic data only possible through the inclusion of dynamical
      correlation.

PMID- 24116615
TI  - Updated potential energy function of the Rb2 a(3)Sigmau(+) state in the
      attractive and repulsive regions determined from its joint analysis with the
      2(3)Pi0g state.
AB  - We report new experimental data for the Rb2 a(3)Sigmau(+) and 2(3)Pi0g states
      obtained using the Perturbation Facilitated Infrared-Infrared Double Resonance
      (PFIIDR) technique. The results include ro-vibrational term values of the
      2(3)Pi0g state and resolved fluorescence spectra of the 2(3)Pi0g->a(3)Sigmau(+)
      transitions for a wide range of rotational and vibrational quantum numbers. An
      analysis of these data confirms the initial assignment of the transitions to the
      a(3)Sigmau(+) state reported in our earlier work [B. Beser, V. B. Sovkov, J. Bai,
      E. H. Ahmed, C. C. Tsai, F. Xie, L. Li, V. S. Ivanov, and A. M. Lyyra, J. Chem.
      Phys. 131, 094505 (2009)]. The potential energy functions of the Rb2
      a(3)Sigmau(+) and 2(3)Pi0g states are derived from a simultaneous fit of the
      available experimental data. The improved potential function of the Rb2
      a(3)Sigmau(+) state spans both the attractive and repulsive regions starting with
      internuclear distance R ~ 4.5 A.

PMID- 24116616
TI  - Towards microscopic assignment of oscillative signatures in two-dimensional
      electronic photon-echo signals of vibronic oligomers: a vibronic dimer model.
AB  - We employ multi-level Redfield theory and the equation-of-motion phase-matching
      approach to model two-dimensional electronic photon-echo signals of a vibronic
      dimer weakly coupled to an uncorrelated harmonic bath. The vibronic manifold of
      the dimer is formed by Franck-Condon active vibrational modes (one mode per
      monomer). We study the effect of the coupled exciton-vibrational dynamics on the
      two-dimensional photon-echo profiles. Our main focus is the relationship of the
      system coherences to the oscillatory behavior of the cross-peak intensities with
      population time. The work represents the first step towards detailed
      understanding of oscillative signatures in two-dimensional electronic photon-echo
      signals of vibronic oligomers. 

PMID- 24116617
TI  - Highly accurate potential energy surface for the He-H2 dimer.
AB  - A new highly accurate interaction potential is constructed for the He-H2 van der
      Waals complex. This potential is fitted to 1900 ab initio energies computed at
      the very large-basis coupled-cluster level and augmented by corrections for
      higher-order excitations (up to full configuration interaction level) and the
      diagonal Born-Oppenheimer correction. At the vibrationally averaged H-H bond
      length of 1.448736 bohrs, the well depth of our potential, 15.870 +/- 0.065 K, is
      nearly 1 K larger than the most accurate previous studies have indicated. In
      addition to constructing our own three-dimensional potential in the van der Waals
      region, we present a reparameterization of the Boothroyd-Martin-Peterson
      potential surface [A. I. Boothroyd, P. G. Martin, and M. R. Peterson, J. Chem.
      Phys. 119, 3187 (2003)] that is suitable for all configurations of the triatomic
      system. Finally, we use the newly developed potentials to compute the properties
      of the lone bound states of (4)He-H2 and (3)He-H2 and the interaction second
      virial coefficient of the hydrogen-helium mixture. 

PMID- 24116618
TI  - Internal energy selection in vacuum ultraviolet photoionization of ethanol and
      ethanol dimers.
AB  - Internal energy selected ethanol monomer and ethanol dimer ions were prepared by
      threshold photoionization of a supersonic molecular beam seeded with ethanol. The
      dissociative photoionization processes of the monomer, the lowest-energy CH3-loss
      channel of the dimer, and the fragmentation of larger clusters were found to be
      disjunct from the ionization onset to about 12 eV, which made it possible to
      determine the 0 K appearance energy of C-C bond breaking in the H-donor unit of
      the ethanol dimer cation as 9.719 +/- 0.004 eV. This reaction energy is used
      together with ab initio calculations in a thermochemical cycle to determine the
      binding energy change from the neutral ethanol dimer to a protonated ethanol
      formaldehyde adduct. The cycle also shows general agreement between experiment,
      theory, and previously published enthalpies of formation. The role of the initial
      ionization site, or rather the initial photoion state, is also discussed based on
      the dimer breakdown diagram and excited state calculations. There is no evidence
      for isolated state behavior, and the ethanol dimer dissociative photoionization
      processes appear to be governed by statistical theory and the ground electronic
      state of the ion. In the monomer breakdown diagram, the smoothly changing
      branching ratio between H and CH3 loss is at odds with rate theory predictions,
      and shows that none of the currently employed few-parameter rate models,
      appropriate for experimental rate curve fitting, yields a correct description for
      this process in the experimental energy range. 

PMID- 24116619
TI  - A combined photoelectron spectroscopy and ab initio study of the quasi-planar
      B24(-) cluster.
AB  - The structure and chemical bonding of the 24-atom boron cluster are investigated
      using photoelectron spectroscopy and ab initio calculations. The joint
      experimental and theoretical investigation shows that B24(-) possesses a quasi
      planar structure containing fifteen outer and nine inner atoms with six of the
      inner atoms forming a filled pentagonal moiety. The central atom of the
      pentagonal moiety is puckered out of plane by 0.9 A, reminiscent of the six-atom
      pentagonal caps of the well-known B12 icosahedral unit. The next closest isomer
      at the ROCCSD(T) level of theory has a tubular double-ring structure. Comparison
      of the simulated spectra with the experimental data shows that the global minimum
      quasi-planar B24(-) isomer is the major contributor to the observed photoelectron
      spectrum, while the tubular isomer has no contribution to the experiment.
      Chemical bonding analyses reveal that the periphery of the quasi-planar B24
      constitutes 15 classical 2c-2e B-B sigma-bonds, whereas delocalized sigma- and pi
      bonds are found in the interior of the cluster with one unique 6c-2e pi-bond
      responsible for bonding in the B-centered pentagon. The current work suggests
      that the 24-atom boron cluster continues to be quasi-2D, albeit the tendency to
      form filled pentagonal units, characteristic of 3D cage-like structures of bulk
      boron, is observed.

PMID- 24116620
TI  - Phase transformations and vibrational properties of coronene under pressure.
AB  - Both the vibrational and structural properties of coronene have been investigated
      upon compression up to 30.5 GPa at room temperature by a combination of Raman
      scattering and synchrotron x-ray diffraction measurements. The spectroscopic and
      crystallographic results demonstrate that two pressure-induced structural phase
      transitions take place at 1.5 GPa and 12.2 GPa where the high-pressure phases are
      identified as monoclinic and orthorhombic crystal structures with space groups of
      P2/m and Pmmm, respectively. A kink in the slope of the cell parameters as a
      function of pressure is associated with the disappearance of several internal
      Raman modes, which suggests the existence of structural distortions or
      reorganizations at approximately 6.0 GPa. Above 17.1 GPa, almost no evidence of
      crystallinity can be observed, indicating a possible transformation of coronene
      into an amorphous phase. 

PMID- 24116621
TI  - A prototypical ionic liquid explored by ab initio molecular dynamics and Raman
      spectroscopy.
AB  - We present an analysis of the liquid and of a small isolated cluster of n-ethyl
      ammonium nitrate based on "first principles" molecular dynamics. We discover that
      the peculiar properties of ionic liquids make such compounds ideal candidates for
      such an analysis. We have been able to characterize some important features of
      the liquid structure and we have validated our simulations by comparing our
      findings with experimental vibrational spectra of the liquid phase. Theoretical
      spectra, which present a remarkable agreement with the measurements, besides the
      assignment of the main spectra features, allow an interpretation of the spectra
      at high frequencies where the vibrational motions involve the hydrogen-bonded
      atoms, thus providing a picture of the hydrogen bonding network that exists in
      such compounds. 

PMID- 24116622
TI  - Constrained molecular vibration-rotation Hamiltonians: contravariant metric
      tensor.
AB  - Here, I present a practical recipe for obtaining contravariant vibration-rotation
      metric tensors, and thus the kinetic energy operators, when some degrees of
      freedom are constrained rigidly. An element of the contravariant metric tensor is
      obtained as a sum of dot products of contravariant measuring vectors, which are
      obtained from their unconstrained counterparts by adding a frozen mode
      correction. The present method applies in principle for any choice of shape
      coordinates and a body-frame for which the contravariant measuring vectors can be
      evaluated. In contrast to the existing methods, the present method does not
      involve evaluation of covariant metric tensors, matrix inversions, chain rules of
      derivation, or numerical differentiation. It is applied in the sequel paper [L.
      Partanen, J. Pesonen, E. Sjoholm, and L. Halonen, J. Chem. Phys. 139, 144311
      (2013)] to study the effects of several different approximations to the kinetic
      energy operator, when the two large-amplitude OH-torsional motions in H2SO4 are
      of interest. 

PMID- 24116623
TI  - A rotamer energy level study of sulfuric acid.
AB  - It is a common approach in quantum chemical calculations for polyatomic molecules
      to rigidly constrain some of the degrees of freedom in order to make the
      calculations computationally feasible. However, the presence of the rigid
      constraints also affects the kinetic energy operator resulting in the frozen mode
      correction, originally derived by Pesonen [J. Chem. Phys. 139, 144310 (2013)]. In
      this study, we compare the effects of this correction to several different
      approximations to the kinetic energy operator used in the literature, in the
      specific case of the rotamer energy levels of sulfuric acid. The two stable
      conformers of sulfuric acid are connected by the rotations of the O-S-O-H
      dihedral angles and possess C2 and Cs symmetry in the order of increasing energy.
      Our results show that of the models tested, the largest differences with the
      frozen mode corrected values were obtained by simply omitting the passive degrees
      of freedom. For the lowest 17 excited states, this inappropriate treatment
      introduces an increase of 9.6 cm(-1) on average, with an increase of 8.7 cm(-1)
      in the zero-point energies. With our two-dimensional potential energy surface
      calculated at the CCSD(T)-F12a/VDZ-F12 level, we observe a radical shift in the
      density of states compared to the harmonic picture, combined with an increase in
      zero point energy. Thus, we conclude that the quantum mechanical inclusion of the
      different conformers of sulfuric acid have a significant effect on its
      vibrational partition function, suggesting that it will also have an impact on
      the computational values of the thermodynamic properties of any reactions where
      sulfuric acid plays a role. Finally, we also considered the effect of the
      anharmonicities for the other vibrational degrees of freedom with a VSCF
      calculation at the DF-MP2-F12/VTZ-F12 level of theory but found that the
      inclusion of the other conformer had the more important effect on the vibrational
      partition function. 

PMID- 24116624
TI  - Vibrational relaxation of chloroiodomethane in cold argon.
AB  - Electronically exciting the C-I stretch in the molecule chloroiodomethane CH2ClI
      embedded in a matrix of argon at 12 K can lead to an isomer, iso
      chloroiodomethane CH2Cl-I, that features a chlorine iodine bond. By temporally
      probing the isomer at two different frequencies of 435 nm and 485 nm, multiple
      timescales for isomerization and vibrational energy relaxation were inferred [T.
      J. Preston, et al., J. Chem. Phys. 135, 114503 (2011)]. This relaxation is
      studied theoretically using molecular dynamics by considering 2 and 3 dimensional
      models. Multiple decay rate constants of the same order of magnitude as the
      experiment are observed. These decay rate constants are interpreted within the
      context of the Landau-Teller theory. Sensitivity of the decay rate constants on
      the bath and system parameters shed more light into the mechanism of vibrational
      energy relaxation. 

PMID- 24116626
TI  - Vibrational fine structure of C5 via anion slow photoelectron velocity-map
      imaging.
AB  - High-resolution anion photoelectron spectra of cryogenically cooled C5(-)
      clusters are reported using slow photoelectron velocity-map imaging spectroscopy.
      We resolve vibronic transitions to the nu2 stretching mode and multiply excited
      nu5, nu6, and nu7 bending modes of neutral C5 with significantly higher accuracy
      than previous experiments. Weak transitions to Franck-Condon (FC) forbidden
      singly excited bending modes are made possible by Herzberg-Teller coupling
      between electronic states of the neutral cluster. In addition, we resolve
      vibrational fine structure corresponding to different angular momentum states of
      multiply excited bending modes. The observation of this multiplet structure, some
      of which is FC forbidden, is attributed to Renner-Teller coupling between
      vibrational levels in the C5(-) ground electronic state.

PMID- 24116625
TI  - Ultraviolet spectroscopy of fundamental lignin subunits: guaiacol, 4
      methylguaiacol, syringol, and 4-methylsyringol.
AB  - Ultraviolet spectroscopy of the G- and S-type lignin subunits, guaiacol (G) and
      syringol (S), along with their para-methylated derivatives 4-methylguaiacol (4
      MG) and 4-methylsyringol (4-MS), has been carried out in the cold, isolated
      environment of a supersonic jet. The excitation spectra and dispersed
      fluorescence (DFL) spectra of G and 4-MG show strong S0-S1 origins and Franck
      Condon activity involving both the ring modes typical of aromatic derivatives,
      and the four lowest frequency out-of-plane modes (a") and lowest in-plane mode
      (a') involving the OH and OCH3 groups. The four low-frequency out-of-plane modes
      undergo extensive Duschinsky mixing between the ground and excited state. In 4
      MG, combination bands involving methyl rotor levels with out-of-plane modes
      appeared with surprisingly high intensity, indicating a high degree of hindered
      rotor-vibration coupling in both S0 and S1. These mixing effects accompany the
      change in geometry upon pi-pi* electronic excitation going from a planar ground
      state to a non-planar excited state. Time-dependent density functional theory
      (TDDFT M05-2X/6-311++G(d,p)) calculations predict a geometric distortion along
      the out-of-plane oxygen flapping coordinate, yielding a double minimum potential
      in S1 with a barrier to planarity of 195 cm(-1) in G. The excitation spectrum of
      S and 4-MS showed a much higher degree of spectral congestion and a larger
      geometry change evident by a shifted intensity distribution peaking ~300 cm(-1)
      above the electronic origin. TDDFT calculations predict a larger geometry change
      in S compared with G, with the OH and H-bonded methoxy groups displaced in
      opposite directions above/below the ring plane. Dispersed fluorescence from all
      S1 excited state levels in S/4-MS yield only broad emission peaking far to the
      red of the excitation wavelength (-4500 cm(-1)). Several hypotheses regarding the
      source of this broad, redshifted emission were tested, but the cause remains
      unclear. p-Methylation was found to significantly redshift the UV absorption in
      both 4-MG and 4-MS, and methyl rotor transitions were assigned in both allowing
      for the determination of the shape and barrier heights of their respective
      potentials. These results provide a foundation for the discrimination of G- and S
      chromophores in lignin oligomers, and demonstrate the potential for site
      selective absorption. 

PMID- 24116627
TI  - Quantum effects in the capture of charged particles by dipolar polarizable
      symmetric top molecules. II. Interplay between electrostatic and gyroscopic
      interactions.
AB  - Within the general axially nonadiabatic channel approach described in Paper I of
      this series [M. Auzinsh, E. I. Dashevskaya, I. Litvin, E. E. Nikitin, and J.
      Troe, J. Chem. Phys. 139, 084311 (2013)], the present article analyzes the
      simultaneous manifestation of electrostatic and gyroscopic interactions in the
      quantum capture of dipolar polarizable symmetric top molecules by ions. As a
      demonstration, the rate coefficients for capture of CH3D and CD3H by H(+), D(+),
      and H3(+) are calculated.

PMID- 24116628
TI  - Hunt for geometric phase effects in H + HD -> HD(v', j') + H.
AB  - An attempt has been made to measure the theoretically predicted manifestation of
      a geometric phase in the differential cross section for the H + HD -> HD(v' = 2,
      j' = 5) + H reaction at a center-of-mass collision energy of 1.44 eV (33.2
      kcal/mol). Minute oscillatory differences between calculated differential cross
      sections that take into account and ignore the effect of geometric phase have
      proven to be beyond our experimental resolution in spite of the collection of
      more than 44,000 ions.

PMID- 24116629
TI  - Ice nucleation by electric surface fields of varying range and geometry.
AB  - Molecular dynamics simulations are employed to show that electric field bands
      acting only over a portion of a surface can function as effective ice nuclei.
      Field bands of different geometry (rectangular, triangular, and semicircular
      cross sectional areas are considered) all nucleate ice, provided that the band is
      sufficiently large. Rectangular bands are very efficient if the width and
      thickness are ?0.35 nm, and ?0.15 nm, respectively, and the necessary dimensions
      are comparable for other geometries. From these simulations we also learn more
      about the ice nucleation and growth process. Careful analysis of different
      systems reveals that ice strongly prefers to grow at (111) planes of cubic ice.
      This agrees with an earlier theoretical deduction based on considerations of
      water-ice interfacial energies. We find that ice nucleated by field bands usually
      grows as a mixture of cubic and hexagonal ice, consistent with other simulations
      of ice growth, and with experiment. This contrasts with simulations carried out
      with nucleating fields that span the entire surface area, where cubic ice
      dominates, and hexagonal layers are very rarely observed. We argue that this
      discrepancy is a simulation artifact related to finite sample size and periodic
      boundary conditions. 

PMID- 24116630
TI  - On fluid-solid direct coexistence simulations: the pseudo-hard sphere model.
AB  - We investigate methodological issues concerning the direct coexistence method, an
      increasingly popular approach to evaluate the solid-fluid coexistence by means of
      computer simulations. The first issue is the impact of the simulation ensemble on
      the results. We compare the NpT ensemble (easy to use but approximate) with the
      NpzT ensemble (rigorous but more difficult to handle). Our work shows that both
      ensembles yield similar results for large systems (>5000 particles). Another
      issue, which is usually disregarded, is the stochastic character of a direct
      coexistence simulation. Here, we assess the impact of stochasticity in the
      determination of the coexistence point. We demonstrate that the error generated
      by stochasticity is much larger than that caused by the use of the NpT ensemble,
      and can be minimized by simply increasing the system size. To perform this study
      we use the pseudo hard-sphere model recently proposed by Jover et al. [J. Chem.
      Phys. 137, 144505 (2012)], and obtain a coexistence pressure of p* = 11.65(1),
      quite similar to that of hard spheres (only about 0.6% higher). Therefore, we
      conclude that this model can be reliably used to investigate the physics of hard
      spheres in phenomena like crystal nucleation. 

PMID- 24116631
TI  - Dynamics of glass-forming liquids. XVII. Dielectric relaxation and intermolecular
      association in a series of isomeric octyl alcohols.
AB  - It is well established that many mono-hydroxy alcohols show an extra relaxation
      process of the Debye type in addition to the signatures of primary and secondary
      structural relaxations, which is observed only in dielectric spectroscopy and
      related techniques. In order to gain further insight into the nature of this
      Debye peak, we study the linear and nonlinear dielectric behavior of a series of
      isomeric octyl alcohols and of mixtures of n-propanol with one of the octanols.
      These samples display systematic variations of the Debye peak intensity and
      concomitant changes in the Kirkwood correlation factor gK from 0.1 to 4,
      indicative of different equilibrium constants, K(c/r), that characterize the
      populations of non-polar ring and polar open chain structures. For cases where
      K(c/r) is not too far from unity, we find that a high electric field shifts
      K(c/r) towards more chains, and that the accompanying change in the end-to-end
      vector of hydrogen-bond connected structures occurs on the Debye time scale. The
      results suggest that gK is correlated with the spectral separation of the Debye
      and primary structural peaks, as both features depend on steric hindrance of
      chain flexibility or bond rotation barriers and on average chain lengths. Based
      on the complex dynamics of supercooled mono-hydroxy alcohols with three
      relaxation peaks that cover many orders of magnitude in frequency, it is argued
      that a frequency dependent gK may be required for assessing the average
      orientational correlations within hydrogen-bonded structures correctly.

PMID- 24116632
TI  - Computation of thermodynamic and transport properties to predict thermophoretic
      effects in an argon-krypton mixture.
AB  - Thermophoresis is the movement of molecules caused by a temperature gradient.
      Here we report the results of a study of thermophoresis using non-equilibrium
      molecular dynamics simulations of a confined argon-krypton fluid subject to two
      different temperatures at thermostated walls. The resulting temperature profile
      between the walls is used along with the Soret coefficient to predict the
      concentration profile that develops across the channel. We obtain the Soret
      coefficient by calculating the mutual diffusion and thermal diffusion
      coefficients. We report an appropriate method for calculating the transport
      coefficients for binary systems, using the Green-Kubo integrals and radial
      distribution functions obtained from equilibrium molecular dynamics simulations
      of the bulk fluid. Our method has the unique advantage of separating the mutual
      diffusion and thermal diffusion coefficients, and calculating the sign and
      magnitude of their individual contributions to thermophoresis in binary mixtures.

PMID- 24116633
TI  - Model vapor-deposited glasses: growth front and composition effects.
AB  - A growing body of experimental work indicates that physical vapor deposition
      provides an effective route for preparation of stable glasses, whose properties
      correspond in some cases to those expected for glasses that have been aged for
      thousands of years. In this work, model binary glasses are prepared in a process
      inspired by physical vapor deposition, in which particles are sequentially added
      to the free surface of a growing film in molecular dynamics simulations. The
      resulting glasses are shown to be more stable than those prepared by gradual
      cooling from the liquid phase. However, it is also shown that the composition of
      the resulting glass, which is difficult to control in physical vapor deposition
      simulations of thin films, plays a significant role on the physical
      characteristics of the material. That composition dependence leads to a re
      evaluation of previous results from simulations of thinner films than those
      considered here, where the equivalent age of the corresponding glasses was
      overestimated. The simulations presented in this work, which correspond to films
      that are approximately 38 molecular diameters thick, also enable analysis of the
      devitrification mechanism by which vapor-deposited glasses transform into the
      supercooled liquid. Consistent with experiments, it is found that this mechanism
      consists of a mobility front that propagates from the free interface into the
      interior of the films. Eliminating surface mobility eliminates this route of
      transformation into the supercooled liquid. 

PMID- 24116634
TI  - A first-principles based force-field for Li+ and OH- in ethanolic solution.
AB  - We report on the development of force-field parameters for accurately modeling
      lithium and hydroxide ions in ethanol in solution. Based on quantum calculations
      of small molecular clusters mimicking the solvent structure of individual ions as
      well as the solvated LiOH dimer, significant improvements of off-the-shelf force
      fields are obtained. The quality of our model is demonstrated by comparison to ab
      initio molecular dynamics of the bulk solution and to experimental data available
      for ethanol/water mixtures. 

PMID- 24116636
TI  - Size dependent elastic moduli of CdSe nanocrystal superlattices predicted from
      atomistic and coarse grained models.
AB  - Nanocrystal superlattices are materials formed by assembly of monodisperse
      nanocrystal building blocks that are tunable in composition, size, shape, and
      surface functionalization. Such materials offer the potential to realize
      unprecedented combinations of physical properties, but theoretical prediction of
      such properties, particularly elastic properties, remains a challenge. Here we
      report the Young's moduli, bulk moduli, and Poisson's ratios of CdSe nanocrystal
      superlattices computed from fully atomistic molecular dynamics simulations,
      coarse grained models, and effective medium theory. The atomistic simulations
      yield Young's moduli in the 4-5 GPa range, in agreement with previously reported
      results for similar nanocrystal superlattice systems. A clear increase of Young's
      modulus and bulk modulus with increasing nanocrystal core size is observed, while
      Poisson's ratio decreases slightly with core size. Effective medium theory
      overpredicts the moduli, and it is surmised that this arises from its neglect of
      the atomic-level details of the of the core-ligand interface. The coarse grained
      calculations, using existing nanocrystal interaction models from the literature,
      also show similar increases with core size but predict moduli that are two orders
      of magnitude lower than the present atomistic results and previous literature. It
      is concluded that coarse grained models, in their current form, are not
      appropriate for calculating elastic properties of nanocrystal superlattices and
      that fully atomistic models are better suited for this purpose. 

PMID- 24116635
TI  - On the molecular origin of high-pressure effects in nanoconfinement: the role of
      surface chemistry and roughness.
AB  - Experiments and simulations both suggest that the pressure experienced by an
      adsorbed phase confined within a carbon nanoporous material can be several orders
      of magnitude larger than the bulk phase pressure in equilibrium with the system.
      To investigate this pressure enhancement, we report a molecular-simulation study
      of the pressure tensor of argon confined in slit-shaped nanopores with walls of
      various models, including carbon and silica materials. We show that the pressure
      is strongly enhanced by confinement, arising from the effect of strongly
      attractive wall forces; confinement within purely repulsive walls does not lead
      to such enhanced pressures. Simulations with both the Lennard-Jones and Barker
      Fisher-Watts intermolecular potentials for argon-argon interactions give rise to
      similar results. We also show that an increase in the wall roughness
      significantly decreases the in-pore pressure due to its influence on the
      structure of the adsorbate. Finally, we demonstrate that the pressures calculated
      from the mechanical (direct pressure tensor calculations) and the thermodynamic
      (volume perturbation method) routes yield almost identical results, suggesting
      that both methods can be used to calculate the local pressure tensor components
      in the case of these planar geometries. 

PMID- 24116637
TI  - Enhanced many-body effects in 2- and 1-dimensional ZnO structures: a Green's
      function perturbation theory study.
AB  - In order to study many-body effects in ZnO structures with reduced
      dimensionality, electronic and optical absorption properties of ZnO monolayer and
      armchair ZnO nanoribbons (AZnONRs) are studied by means of Green's function
      perturbation theory using the GW+Bethe-Salpeter equation approach. In both ZnO
      monolayer and AZnONRs, as a consequence of enhanced quantum confinement, the
      quasi-particle corrections are significant and the optical absorption properties
      are dominated by strong excitonic effects with considerable binding energies (1-2
      eV) assigned to the lowest-energy bound excitons. It reveals that inclusion of
      excitonic effects, which are neglected in calculations at single-particle
      approximation, is crucial to qualitatively and quantitatively describe the
      optical properties of such materials with reduced-dimensionality. 

PMID- 24116638
TI  - Spherulitic crystallization in binary thin films under solvent-vapor annealing.
      I. A sharp-interface theory.
AB  - We present a thermodynamically consistent theory for solvent-vapor induced
      spherulitic crystallization in binary thin-film blends, including those which
      consist of polymeric or organic small-molecule semiconductors. Under the proposed
      theory, spherulitic growth is interface driven, with no diffusion of any species.
      The thermodynamic driving force at the interface between the spherulite and
      amorphous phase is identified, and a kinetic relation that delivers a constant
      growth rate is proposed. 

PMID- 24116639
TI  - The atomic and electronic structures of NiO(001)/Au(001) interfaces.
AB  - The atomic and electronic structures of NiO(001)/Au(001) interfaces were analyzed
      by high-resolution medium energy ion scattering (MEIS) and photoelectron
      spectroscopy using synchrotron-radiation-light. The MEIS analysis clearly showed
      that O atoms were located above Au atoms at the interface and the inter-planar
      distance of NiO(001)/Au(001) was derived to be 2.30 +/- 0.05 A, which was
      consistent with the calculations based on the density functional theory (DFT). We
      measured the valence band spectra and found metallic features for the NiO
      thickness up to 3 monolayer (ML). Relevant to the metallic features, electron
      energy loss analysis revealed that the bandgap for NiO(001)/Au(001) reduced with
      decreasing the NiO thickness from 10 down to 5 ML. We also observed Au 4f lines
      consisting of surface, bulk, and interface components and found a significant
      electronic charge transfer from Au(001) to NiO(001). The present DFT calculations
      demonstrated the presence of an image charge beneath Ni atoms at the interface
      just like alkali-halide/metal interface, which may be a key issue to explain the
      core level shift and band structure. 

PMID- 24116640
TI  - Sedimentation of a two-dimensional colloidal mixture exhibiting liquid-liquid and
      gas-liquid phase separation: a dynamical density functional theory study.
AB  - We present dynamical density functional theory results for the time evolution of
      the density distribution of a sedimenting model two-dimensional binary mixture of
      colloids. The interplay between the bulk phase behaviour of the mixture, its
      interfacial properties at the confining walls, and the gravitational field gives
      rise to a rich variety of equilibrium and non-equilibrium morphologies. In the
      fluid state, the system exhibits both liquid-liquid and gas-liquid phase
      separation. As the system sediments, the phase separation significantly affects
      the dynamics and we explore situations where the final state is a coexistence of
      up to three different phases. Solving the dynamical equations in two-dimensions,
      we find that in certain situations the final density profiles of the two species
      have a symmetry that is different from that of the external potentials, which is
      perhaps surprising, given the statistical mechanics origin of the theory. The
      paper concludes with a discussion on this. 

PMID- 24116641
TI  - Discrete model studies of two grafted polyelectrolyte polymer hydrogels pressed
      in contact.
AB  - The interaction between two grafted polymer gels was investigated. We studied a
      defect-free network of diamond-like topology containing 8 tetra-functional nodes
      linked by 16 non-crossing chains. In order to explain the very low friction
      coefficient observed for polyelectrolyte hydrogels, we computed the monomer
      density profile of these polymer gels, the interpenetration between two polymer
      gels (defined as the percentage of monomers belonging to one gel which have
      penetrated the second gel), the normal force per unit area, and the radial
      distribution function of the interacting monomers. Low monomer density in the
      interface region separating the two gels and low interpenetration of the gels
      similar to that found in our simulations are likely to be responsible for the
      small friction coefficients observed for polyelectrolyte polymer gels. 

PMID- 24116643
TI  - Percolation of high-density polymer regions in nanocomposites: the underlying
      property for mechanical reinforcement.
AB  - Polymer nanocomposites have shown to exhibit improved mechanical properties
      compared to their pure host polymers. These property changes have been primarily
      attributed to the nature of polymer/nanoparticle interactions. Molecular dynamics
      simulations of model polymer nanocomposites have provided new insights into the
      molecular origin of property-changes in these nanocomposites. It was observed
      that addition of nanoparticles, induced adsorption of monomer segments onto the
      surface of nanoparticles creating high-density regions of polymer segments in the
      interfacial zones. A closer look into the morphology of these regions surrounding
      the nanoparticles revealed that mechanical reinforcement and changes in flow
      properties may be attributed to the formation of a percolated network of these
      high-density regions. 

PMID- 24116642
TI  - An experimentally-informed coarse-grained 3-Site-Per-Nucleotide model of DNA:
      structure, thermodynamics, and dynamics of hybridization.
AB  - A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model
      includes anisotropic potentials between bases involved in base stacking and base
      pair interactions that enable the description of relevant structural properties,
      including the major and minor grooves. In an improvement over available coarse
      grained models, the correct persistence length is recovered for both ssDNA and
      dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA
      melting temperatures, measured for duplexes and hairpins by integrating over free
      energy surfaces generated using metadynamics simulations, are shown to be in
      quantitative agreement with experiment for a variety of sequences and conditions.
      Hybridization rate constants, calculated using forward-flux sampling, are also
      shown to be in good agreement with experiment. The coarse-grained model presented
      here is suitable for use in biological and engineering applications, including
      nucleosome positioning and DNA-templated engineering. 

PMID- 24116644
TI  - Fracture energy of polymer gels with controlled network structures.
AB  - We have investigated the fracture behaviors of tetra-arm polyethylene glycol
      (Tetra-PEG) gels with controlled network structures. Tetra-PEG gels were prepared
      by AB-type crosslink-coupling of mutually reactive tetra-arm prepolymers with
      different concentrations and molecular weights. This series of controlled network
      structures, for the first time, enabled us to quantitatively examine the Lake
      Thomas model, which is the most popular model predicting fracture energies of
      elastomers. The experimental data showed good agreement with the Lake-Thomas
      model, and indicated a new molecular interpretation for the displacement length
      (L), the area around a crack tip within which the network strands are fully
      stretched. L corresponded to the three times of end-to-end distance of network
      strands, regardless of all parameters examined. We conclude that the Lake-Thomas
      model can quantitatively predict the fracture energy of polymer network without
      trapped entanglements, with the enhancement factor being near 3. 

PMID- 24116645
TI  - Layerwise decomposition of water dynamics in reverse micelles: a simulation study
      of two-dimensional infrared spectrum.
AB  - We present computer simulation study of two-dimensional infrared spectroscopy (2D
      IR) of water confined in reverse micelles (RMs) of various sizes. The present
      study is motivated by the need to understand the altered dynamics of confined
      water by performing layerwise decomposition of water, with an aim to quantify the
      relative contributions of different layers water molecules to the calculated 2D
      IR spectrum. The 0-1 transition spectra clearly show substantial elongation, due
      to inhomogeneous broadening and incomplete spectral diffusion, along the diagonal
      in the surface water layer of different sized RMs. Fitting of the frequency
      fluctuation correlation functions reveal that the motion of the surface water
      molecules is sub-diffusive and indicate the constrained nature of their dynamics.
      This is further supported by two peak nature of the angular analogue of van Hove
      correlation function. With increasing system size, the water molecules become
      more diffusive in nature and spectral diffusion almost completes in the central
      layer of the larger size RMs. Comparisons between experiments and simulations
      establish the correspondence between the spectral decomposition available in
      experiments with the spatial decomposition available in simulations. Simulations
      also allow a quantitative exploration of the relative role of water, sodium ions,
      and sulfonate head groups in vibrational dephasing. Interestingly, the negative
      cross correlation between force on oxygen and hydrogen of O-H bond in bulk water
      significantly decreases in the surface layer of each RM. This negative cross
      correlation gradually increases in the central water pool with increasing RMs
      size and this is found to be partly responsible for the faster relaxation rate of
      water in the central pool. 

PMID- 24116646
TI  - Evidence for several dipolar quasi-invariants in liquid crystals.
AB  - The quasi-equilibrium states of an observed quantum system involve as many
      constants of motion as the dimension of the operator basis which spans the blocks
      of all the degenerate eigenvalues of the Hamiltonian that drives the system
      dynamics, however, the possibility of observing such quasi-invariants in solid
      like spin systems in Nuclear Magnetic Resonance (NMR) is not a strictly exact
      prediction. The aim of this work is to provide experimental evidence of several
      quasi-invariants, in the proton NMR of small spin clusters, like nematic liquid
      crystal molecules, in which the use of thermodynamic arguments is not justified.
      We explore the spin states prepared with the Jeener-Broekaert pulse sequence by
      analyzing the time-domain signals yielded by this sequence as a function of the
      preparation times, in a variety of dipolar networks, solids, and liquid crystals.
      We observe that the signals can be explained with two dipolar quasi-invariants
      only within a range of short preparation times, however at longer times liquid
      crystal signals show an echo-like behaviour whose description requires assuming
      more quasi-invariants. We study the multiple quantum coherence content of such
      signals on a basis orthogonal to the z-basis and see that such states involve a
      significant number of correlated spins. Therefore, we show that the NMR signals
      within the whole preparation time-scale can only be reconstructed by assuming the
      occurrence of multiple quasi-invariants which we experimentally isolate. 

PMID- 24116647
TI  - Proton transfer in oxidized adenosine self-aggregates.
AB  - The UV-vis and the IR spectra of derivativized adenosine in dichloromethane have
      been recorded during potentiostatic oxidation at an optically transparent thin
      layer electrode. Oxidized adenosine shows a broad Zundel like absorption
      extending from 2800 up to 3600 cm(-1), indicating that a proton transfer process
      is occurring. Theoretical computations predict that proton transfer is indeed
      favored in oxidized 1:1 self-association complexes and allow to assign all the
      observed transient spectroscopic signals. 

PMID- 24116649
TI  - Protein folding: complex potential for the driving force in a two-dimensional
      space of collective variables.
AB  - Using the Helmholtz decomposition of the vector field of folding fluxes in a two
      dimensional space of collective variables, a potential of the driving force for
      protein folding is introduced. The potential has two components. One component is
      responsible for the source and sink of the folding flows, which represent
      respectively, the unfolded states and the native state of the protein, and the
      other, which accounts for the flow vorticity inherently generated at the
      periphery of the flow field, is responsible for the canalization of the flow
      between the source and sink. The theoretical consideration is illustrated by
      calculations for a model beta-hairpin protein. 

PMID- 24116648
TI  - Molecular recognition of DNA by ligands: roughness and complexity of the free
      energy profile.
AB  - Understanding the molecular mechanism by which probes and chemotherapeutic agents
      bind to nucleic acids is a fundamental issue in modern drug design. From a
      computational perspective, valuable insights are gained by the estimation of free
      energy landscapes as a function of some collective variables (CVs), which are
      associated with the molecular recognition event. Unfortunately the choice of CVs
      is highly non-trivial because of DNA's high flexibility and the presence of
      multiple association-dissociation events at different locations and/or sliding
      within the grooves. Here we have applied a modified version of Locally-Scaled
      Diffusion Map (LSDMap), a nonlinear dimensionality reduction technique for
      decoupling multiple-timescale dynamics in macromolecular systems, to a
      metadynamics-based free energy landscape calculated using a set of intuitive CVs.
      We investigated the binding of the organic drug anthramycin to a DNA 14-mer
      duplex. By performing an extensive set of metadynamics simulations, we observed
      sliding of anthramycin along the full-length DNA minor groove, as well as several
      detachments from multiple sites, including the one identified by X-ray
      crystallography. As in the case of equilibrium processes, the LSDMap analysis is
      able to extract the most relevant collective motions, which are associated with
      the slow processes within the system, i.e., ligand diffusion along the minor
      groove and dissociation from it. Thus, LSDMap in combination with metadynamics
      (and possibly every equivalent method) emerges as a powerful method to describe
      the energetics of ligand binding to DNA without resorting to intuitive ad hoc
      reaction coordinates. 

PMID- 24116650
TI  - Probing the origins of two-state folding.
AB  - Many protein systems fold in a two-state manner. Random models, however, rarely
      display two-state kinetics and thus such behavior should not be accepted as a
      default. While theories for the prevalence of two-state kinetics have been
      presented, none sufficiently explain the breadth of experimental observations. A
      model, making minimal assumptions, is introduced that suggests two-state behavior
      is likely for any system with an overwhelmingly populated native state. We show
      two-state folding is a natural consequence of such two-state thermodynamics, and
      is strengthened by increasing the population of the native state. Further, the
      model exhibits hub-like behavior, with slow interconversions between unfolded
      states. Despite this, the unfolded state equilibrates quickly relative to the
      folding time. This apparent paradox is readily understood through this model.
      Finally, our results compare favorable with measurements of folding rates as a
      function of chain length and Keq, providing new insight into these relations. 

PMID- 24116651
TI  - MuSTAR MD: multi-scale sampling using temperature accelerated and replica
      exchange molecular dynamics.
AB  - A new and efficient conformational sampling method, MuSTAR MD (Multi-scale
      Sampling using Temperature Accelerated and Replica exchange Molecular Dynamics),
      is proposed to calculate the free energy landscape on a space spanned by a set of
      collective variables. This method is an extension of temperature accelerated
      molecular dynamics and can also be considered as a variation of replica-exchange
      umbrella sampling. In the MuSTAR MD, each replica contains an all-atom fine
      grained model, at least one coarse-grained model, and a model defined by the
      collective variables that interacts with the other models in the same replica
      through coupling energy terms. The coarse-grained model is introduced to drive
      efficient sampling of large conformational space and the fine-grained model can
      serve to conduct more accurate conformational sampling. The collective variable
      model serves not only to mediate the coarse- and fine-grained models, but also to
      enhance sampling efficiency by temperature acceleration. We have applied this
      method to Ala-dipeptide and examined the sampling efficiency of MuSTAR MD in the
      free energy landscape calculation compared to that for replica exchange molecular
      dynamics, replica exchange umbrella sampling, temperature accelerated molecular
      dynamics, and conventional MD. The results clearly indicate the advantage of
      sampling a relatively high energy conformational space, which is not sufficiently
      sampled with other methods. This feature is important in the investigation of
      transition pathways that go across energy barriers. MuSTAR MD was also applied to
      Met-enkephalin as a test case in which two Go-like models were employed as the
      coarse-grained model. 

PMID- 24116652
TI  - Comment on "Going beyond the frozen core approximation: development of coordinate
      dependent pseudopotentials and application to Na2(+)" [J. Chem. Phys. 138, 054110
      (2013)].
AB  - The new coordinate-dependent pseudopotential for Na2(+) by Kahros and Schwartz
      [J. Chem. Phys. 138, 054110 (2013)] is assessed and compared to the
      pseudopotential approach by Fuentealba et al. [Chem. Phys. Lett. 89, 418 (1982)]
      which incorporates the coordinate-dependent core-polarization potential by Muller
      and Meyer [J. Chem. Phys. 80, 3311 (1984)]. In contrast to the latter approach,
      the one by Kahros and Schwartz does not reproduce the accurately known
      experimental data and/or high level theoretical results for Na2(+). The treatment
      of core polarization by Kahros and Schwartz neglects the dynamic polarization of
      atomic cores which is much more important for Na2(+) than the static one. On the
      other hand, the Kahros and Schwartz method heavily overestimates frozen-core
      corrections at the Hartree-Fock level by compounding them with artifacts of a
      superposition of non-norm-conserving pseudopotentials.

PMID- 24116653
TI  - Response to "Comment on 'Going beyond the frozen core approximation: development
      of coordinate-dependent pseudopotentials and application to Na2(+)'" [J. Chem.
      Phys. 139, 147101 (2013)].
AB  - Stoll, Fuentealba, and Szentpaly (SFS) argue that the coordinate-dependent
      pseudopotential we developed for the sodium dimer cation molecule is inferior to
      other potentials that have been presented in the literature for this molecule.
      The goal of our work, however, was to present a novel method for the development
      of rigorous coordinate-dependent pseudopotentials. Our method is designed to
      reproduce all-electron Hartree-Fock calculations without the inclusion of
      adjustable parameters. Moreover, our method starts from the superposition of
      unoptimized, non-norm-conserved atomic potentials, so that when complete, the
      resulting norm-conserving potential can reproduce an all-electron Hartree-Fock
      calculation without the inclusion of adjustable parameters. We chose the sodium
      dimer cation system as a proof of principle for our method, and showed that our
      method does indeed allow a one-electron calculation to correctly reproduce the
      all-electron Hartree-Fock calculation from bonding to the dissociation limit. Our
      purpose in developing this method is to use such potentials in condensed-phase
      mixed quantum/classical molecular dynamics simulations, where inclusion of
      valence polarization effects is unimportant or can be added on after the fact.
      Thus we do not claim that our method provides a potential that is superior to
      potentials that have been specifically constructed to go beyond the static
      exchange approximation and/or include valence polarization effects-such
      potentials are beyond the scope of our work. We also note that although we made a
      numerical error in the application of our method to Na2(+) in our original work
      [A. Kahros and B. J. Schwartz, J. Chem. Phys. 138, 054110 (2013)] that led to an
      overestimation of the magnitude of core polarization effects for this particular
      molecule, out method does work as derived for this molecule and the error does
      not affect the significance of our method or its general applicability.

PMID- 24116656
TI  - Automated EEG signal analysis for identification of epilepsy seizures and brain
      tumour.
AB  - Abstract Electroencephalography (EEG) is a clinical test which records neuro
      electrical activities generated by brain structures. EEG test results used to
      monitor brain diseases such as epilepsy seizure, brain tumours, toxic
      encephalopathies infections and cerebrovascular disorders. Due to the extreme
      variation in the EEG morphologies, manual analysis of the EEG signal is
      laborious, time consuming and requires skilled interpreters, who by the nature of
      the task are prone to subjective judegment and error. Further, manual analysis of
      the EEG results often fails to detect and uncover subtle features. This paper
      proposes an automated EEG analysis method by combining digital signal processing
      and neural network techniques, which will remove error and subjectivity
      associated with manual analysis and identifies the existence of epilepsy seizure
      and brain tumour diseases. The system uses multi-wavelet transform for feature
      extraction in which an input EEG signal is decomposed in a sub-signal.
      Irregularities and unpredictable fluctuations present in the decomposed signal
      are measured using approximate entropy. A feed-forward neural network is used to
      classify the EEG signal as a normal, epilepsy or brain tumour signal. The
      proposed technique is implemented and tested on data of 500 EEG signals for each
      disease. Results are promising, with classification accuracy of 98% for normal,
      93% for epilepsy and 87% for brain tumour. Along with classification, the paper
      also highlights the EEG abnormalities associated with brain tumour and epilepsy
      seizure. 

PMID- 24116657
TI  - Vitamin D and physical performance in older men and women visiting the emergency
      department because of a fall: data from the improving medication prescribing to
      reduce risk of falls (IMPROveFALL) study.
AB  - OBJECTIVES: To investigate whether serum 25-hydroxy vitamin D (25(OH)D) is
      associated with physical performance in men and women. DESIGN: Cross-sectional.
      SETTING: Emergency departments (EDs) of five hospitals. PARTICIPANTS: Older
      adults who visited an ED because of a fall (N = 616). MEASUREMENTS: Physical
      performance was assessed using the Timed Up and Go Test, the Five Time Sit to
      Stand Test, handgrip strength, and the tandem stand test. Multivariate linear
      regression was used to assess the association between physical performance and
      log-transformed 25(OH)D concentration adjusted for potential confounders.
      RESULTS: In men, higher serum 25(OH)D concentration was significantly associated
      with better handgrip strength (regression coefficient (B) = 3.86, 95% confidence
      interval (CI) = 2.04-5.69), faster TUG time (B = -2.82, 95% CI = -4.91 to -0.73),
      and faster FTSS time (B = -3.39, 95% CI = -5.67 to -1.11). In women, higher serum
      25(OH)D concentration was significantly associated with faster TUG time (B = 
      2.68, 95% CI = -4.87 to -0.49). CONCLUSION: A positive association was found
      between serum 25(OH)D level and physical performance in men and women.
      Intervention studies are needed of vitamin D-deficient older men and women to
      further investigate the effect of vitamin D supplementation in this group.

PMID- 24116658
TI  - Minor H antigen matches and mismatches are equally distributed among recipients
      with or without complications after HLA identical sibling renal transplantation.
AB  - Studies of the effect of minor H antigen mismatching on the outcome of renal
      transplantation are scarce and concern mainly single center studies. The
      International Histocompatibility and Immunogenetics Workshops (IHIW) provide a
      collaborative platform to execute crucial large studies. In collaboration with 16
      laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor
      H antigens and 3 CD31 polymorphisms, was investigated in relation to the
      incidence of renal graft rejection and graft loss in 444 human leukocyte antigens
      (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples
      were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC
      2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The
      correlation between minor H antigen mismatch and the primary outcome graft
      rejection or graft loss was statistically analyzed. The incidence of rejection
      was very low and no correlation was observed between one or more minor H antigen
      mismatch(es) and a rejection episode (n = 36), of which only eight resulted in
      graft loss. In summary, in our study cohort of 444 renal transplants, mismatching
      for neither autosomal nor HY minor H antigens correlate with rejection episodes
      or with graft loss. 

PMID- 24116659
TI  - The intriguing relationship between cerebral palsy and autism.

PMID- 24116660
TI  - Human papillomavirus type 16-induced skin squamous cell carcinoma located on the
      groin of immunocompetent patients.

PMID- 24116662
TI  - A qualitative study on factors impacting HIV care adherence among postpartum HIV
      infected women in the rural southeastern USA.
AB  - Declines in HIV care and treatment adherence among HIV-infected women from
      pregnancy to the postpartum period have significant implications for the clinical
      outcomes and overall well-being of HIV-infected women, especially due to
      immunosuppression during the postpartum period. While the overall increased risk
      for mortality associated with HIV care discontinuation is well established, the
      reasons for HIV care nonadherence among HIV-infected postpartum women are largely
      unknown. Eighteen HIV-infected women were recruited from four clinics in Alabama
      to participate in focus groups or individual interviews to discuss barriers and
      facilitators impacting postpartum HIV care adherence. Sessions were audio
      recorded, transcribed, and coded; content analysis was used to analyze the
      verbatim transcripts. Mixed methods analysis procedures were used to triangulate
      data from three sources (focus group transcripts, individual rankings of barriers
      and facilitators according to the Nominal Group Technique, and individual
      questionnaires of sociodemographic and adherence data). The majority of
      participants were African-American (83.3%), single (66.7%), with more than half
      of the participants living on less than $1000 a month (55.6%). Barriers to
      retention in HIV care included access to and cost of transportation and fitting
      HIV care into work and childcare schedules. Facilitators to HIV care adherence
      included wanting to stay healthy for their own well-being as well as for the care
      of their children, receiving family support, and appointment reminders. The
      current study highlights contextual factors contributing to poor HIV care
      adherence among HIV-infected postpartum women. Intervention studies need to be
      cognizant of the specific needs of HIV-infected postpartum women to improve long
      term clinical outcomes among this population, who have children. 

PMID- 24116661
TI  - Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2
      (polycystin-2)-dependent manner.
AB  - BACKGROUND AND PURPOSE: Identifying and characterizing potential new therapeutic
      agents to target cell proliferation may provide improved treatments for
      neoplastic disorders such as cancer and polycystic diseases. EXPERIMENTAL
      APPROACH: We used the simple, tractable biomedical model Dictyostelium to
      investigate the molecular mechanism of naringenin, a dietary flavonoid with
      antiproliferative and chemopreventive actions in vitro and in animal models of
      carcinogenesis. We then translated these results to a mammalian kidney model,
      Madin-Darby canine kidney (MDCK) tubule cells, grown in culture and as cysts in a
      collagen matrix. KEY RESULTS: Naringenin inhibited Dictyostelium growth, but not
      development. Screening of a library of random gene knockout mutants identified a
      mutant lacking TRPP2 (polycystin-2) that was resistant to the effect of
      naringenin on growth and random cell movement. TRPP2 is a divalent transient
      receptor potential cation channel, where mutations in the protein give rise to
      type 2 autosomal dominant polycystic kidney disease (ADPKD). Naringenin inhibited
      MDCK cell growth and inhibited cyst growth. Knockdown of TRPP2 levels by siRNA in
      this model conferred partial resistance to naringenin such that cysts treated
      with 3 and 10 MUM naringenin were larger following TRPP2 knockdown compared with
      controls. Naringenin did not affect chloride secretion. CONCLUSIONS AND
      IMPLICATIONS: The action of naringenin on cell growth in the phylogenetically
      diverse systems of Dictyostelium and mammalian kidney cells, suggests a conserved
      effect mediated by TRPP2 (polycystin-2). Further studies will investigate
      naringenin as a potential new therapeutic agent in ADPKD.

PMID- 24116664
TI  - The audiological health of horn players.
AB  - Among orchestral musicians, horn players are one of the most at-risk groups for
      noise-induced hearing loss (NIHL). To investigate this group further, pure tone
      audiometry and a 14-item questionnaire were used to assess the hearing health, as
      well as attitudes and practices regarding hearing conservation, among 142 French
      horn players attending an international horn conference in Brisbane, Australia.
      Of this study's French horn players, 11.1% to 22.2%, and 17.7% to 32.9% of those
      aged <=40 years, showed some form of hearing loss (corrected for age and gender)
      typical of NIHL, using conservative versus lenient criteria, respectively.
      Stepwise multiple regression analyses showed no obvious predictor of hearing loss
      in this study's participants. Of the 18% of participants who reported using
      hearing protection, 81% used this protection "sometimes" and 50% used generic,
      foam, or other inferior forms of protection. Continued efforts to better manage
      the hearing health of horn players is warranted particularly as any hearing loss
      will affect a horn player's ability to perform and therefore his or her
      livelihood. Managing the hearing health of horn players will be challenging,
      however, with no simple predictor of NIHL loss being identified in this study's
      sample.

PMID- 24116663
TI  - Analytical method validation for the determination of 2,3,3,3-tetrafluoropropene
      in air samples using gas chromatography with flame ionization detection.
AB  - A new low global warming refrigerant, 2,3,3,3-tetrafluoro propene, or HFO-1234yf,
      has been successfully evaluated for automotive air conditioning, and is also
      being evaluated for stationary refrigeration and air conditioning systems. Due to
      the advantageous environmental properties of HFO-1234yf versus HFC-134a, coupled
      with its similar physical properties and system performance, HFO-1234yf is also
      being evaluated to replace HFC-134a in refrigeration applications where neat HFC
      134a is currently used. This study reports on the development and validation of a
      sampling and analytical method for the determination of HFO-1234yf in air.
      Different collection media were screened for desorption and simulated sampling
      efficiency with three-section (350/350/350 mg) Anasorb CSC showing the best
      results. Therefore, air samples were collected using two 3-section Anasorb CSC
      sorbent tubes in series at 0.02 L/min for up to 8 hr for sample volumes of up to
      9.6 L. The sorbent tubes were extracted in methylene chloride, and analyzed by
      gas chromatography with flame ionization detection. The method was validated from
      0.1* to 20* the target level of 0.5 ppm (2.3 mg/m(3)) for a 9.6 L air volume.
      Desorption efficiencies for HFO-1234yf were 88 to 109% for all replicates over
      the validation range with a mean overall recovery of 93%. Simulated sampling
      efficiencies ranged from 87 to 104% with a mean of 94%. No migration or
      breakthrough to the back tube was observed under the sampling conditions
      evaluated. HFO-1234yf samples showed acceptable storage stability on Anasorb CSC
      sorbent up to a period of 30 days when stored under ambient, refrigerated, or
      frozen temperature conditions.

PMID- 24116665
TI  - Prevention guidance for isocyanate-induced asthma using occupational surveillance
      data.
AB  - Data from Washington State's work-related asthma surveillance system were used to
      characterize isocyanate-induced asthma cases occurring from 1999 through 2010.
      Injured worker interviews and medical records were used to describe the industry,
      job title, work process, workers' compensation cost, and exposure trends
      associated with 27 cases of isocyanate-induced asthma. The majority (81%) of
      cases were classified within the surveillance system as new-onset asthma while
      19% were classified as work-aggravated asthma. The workers' compensation cost for
      isocyanate-induced asthma cases was $1.7 million; this was 14% of the total
      claims cost for all claims in the asthma surveillance system. The majority of
      cases (48%) occurred from paint processes, followed by foam application or foam
      manufacturing (22%). Nine of the asthma cases associated with spray application
      occurred during application to large or awkward-shaped objects. Six workers who
      did not directly handle isocyanates (indirect exposure) developed new-onset
      asthma. Two cases suggest that skin contact and processes secondary to the
      isocyanate spray application, such as cleanup, contributed to immune
      sensitization. Surveillance data provide insight for the prevention of isocyanate
      induced respiratory disease. Key observations are made regarding the development
      of work-related asthma in association with a) paint application on large objects
      difficult to ventilate, b) indirect exposure to isocyanates, c) exposure during
      secondary or cleanup processes, and d) reports of dermal exposure. 

PMID- 24116666
TI  - Biomonitoring study of dry cleaning workers using cytogenetic tests and the comet
      assay.
AB  - Perchloroethylene (PCE) is the main solvent used in the dry cleaning industry
      worldwide. The aim of the present work was to evaluate the genotoxic potential of
      occupational exposure to PCE in dry cleaning workers. The study was carried out
      in 59 volunteers (30 workers, 29 controls). The genotoxic effect was evaluated by
      analyzing chromosome aberrations (CAs), and micronuclei (MN) and DNA damage
      (assessed by the comet assay) in peripheral blood lymphocytes. Environmental
      monitoring of exposure was carried out on personal breathing zone air samples
      collected during two consecutive working days by measuring the concentration of
      PCE air levels. The mean PCE concentration in workplace air of dry cleaning
      workers was 31.40 mg/m(3). There were no significant differences in CA frequency
      between dry cleaning workers and the controls, but analysis showed a significant
      association of CA frequency with employment duration and frequency of exposure to
      PCE. The MN frequency and DNA damage detected by alkaline comet assay were
      significantly increased in dry cleaning workers compared to the controls. The
      results suggest that (a) chronic occupational exposure to dry cleaning solvents
      below permissible occupational exposure limit of 70 mg/m(3) (i.e., ~10.3 ppm) may
      lead to an increased risk of genetic damage among dry cleaning workers, and (b)
      CA, MN tests, and comet assay are useful to monitor populations exposed to low
      doses of PCE.

PMID- 24116667
TI  - Potential exposures associated with indoor marijuana growing operations.
AB  - We entered a total of 30 indoor marijuana grow operations (IMGO) with law
      enforcement investigators in order to determine potential exposures to first
      responders. Samples for airborne fungal spores, volatile organic compounds,
      carbon dioxide, carbon monoxide, and delta-9-tetrahydrocannabinol (THC) were
      obtained as well as the identification of chemicals utilized in the IMGO. The
      chemicals utilized within the IMGOs were primarily pesticides and fertilizers
      with none showing high toxicity. Although several of the IMGOs had CO2 enrichment
      processes involving combustion, CO levels were not elevated. THC levels were
      identified on surfaces within the IMGOs and on the hands of the investigators.
      Surface levels ranged from <0.1 MUg /100 cm(2) to 2000 MUg /100 cm(2) with a
      geometric mean of 0.37 MUg /100 cm(2). THC levels on the hands of officers ranged
      from <0.10 MUg /wipe to 2900 MUg /wipe with a geometric mean of 15 MUg /wipe.
      These levels were not considered to be elevated to the point of causing a toxic
      exposure to responders. A total of 407 fungal spore samples were taken using both
      slit impactor plates and 400-hole impactors. Both methods identified elevated
      fungal spore levels, especially during the removal of plants from some of the
      IMGOs. After plant removal, spore counts increased to levels above 50,000
      spores/m(3) with one sample over 500,000 spores/m(3). In addition, we found that
      there was a shift in species between indoor and outdoor samples with Cladosporium
      sp. the predominant outdoor species and Penicillium sp. the predominant indoor
      species. We concluded that the potential increase in fungal spore concentrations
      associated with the investigation and especially removal of the marijuana plants
      could potentially expose responders to levels of exposure consistent with those
      associated with mold remediation processes and that respiratory protection is
      advisable.

PMID- 24116668
TI  - Excursion guidance criteria to guide control of peak emission and exposure to
      airborne engineered particles.
AB  - The overall aim of our research was to characterize airborne particles from
      selected nanotechnology processes and to utilize the data to develop and test
      quantitative particle concentration-based criteria that can be used to trigger an
      assessment of particle emission controls. We investigated particle number
      concentration (PNC), particle mass (PM) concentration, count median diameter
      (CMD), alveolar deposited surface area, elemental composition, and morphology
      from sampling of aerosols arising from six nanotechnology processes. These
      included fibrous and non-fibrous particles, including carbon nanotubes (CNTs). We
      adopted standard occupational hygiene principles in relation to controlling peak
      emission and exposures, as outlined by both Safe Work Australia, and the American
      Conference of Governmental Industrial Hygienists (ACGIH(r)). The results from the
      study were used to analyses peak and 30-minute averaged particle number and mass
      concentration values measured during the operation of the nanotechnology
      processes. Analysis of peak (highest value recorded) and 30-minute averaged
      particle number and mass concentration values revealed: Peak PNC(20-1000 nm)
      emitted from the nanotechnology processes were up to three orders of magnitude
      greater than the local background particle concentration (LBPC). Peak PNC(300
      3000 nm) was up to an order of magnitude greater, and PM2.5 concentrations up to
      four orders of magnitude greater. For three of these nanotechnology processes,
      the 30-minute average particle number and mass concentrations were also
      significantly different from the LBPC (p-value < 0.001). We propose emission or
      exposure controls may need to be implemented or modified, or further assessment
      of the controls be undertaken, if concentrations exceed three times the LBPC,
      which is also used as the local particle reference value, for more than a total
      of 30 minutes during a workday, and/or if a single short-term measurement exceeds
      five times the local particle reference value. The use of these quantitative
      criteria, which we are terming the universal excursion guidance criteria, will
      account for the typical variation in LBPC and inaccuracy of instruments, while
      precautionary enough to highlight peaks in particle concentration likely to be
      associated with particle emission from the nanotechnology process.
      Recommendations on when to utilize local excursion guidance criteria are also
      provided.

PMID- 24116669
TI  - Temporal variation of size-fractionated particulate matter and carbon monoxide in
      selected microenvironments of the Milan urban area.
AB  - This article focuses on air pollution in specific urban microenvironments and
      conditions characterized by high relative concentration levels and by possible
      risk to human health. For this reason, monitoring of particle number
      concentration (PNC) with a wide, size-resolved particle-size range, and CO (an
      indicator of combustion sources, e.g., traffic), was performed in a variety of
      microenvironments. Concentrations of ultrafine particles (UFPs), size
      fractionated particulate matter (PM), and carbon monoxide (CO) were measured in
      the central area of Milan over three-week-long periods, one each during summer,
      autumn, and winter, with three monitoring sessions per day. Experimental data
      were collected continuously during each monitoring period along an established
      urban pathway. To assess the relevance of time and spatial factors affecting
      atmospheric concentrations of UFPs, PM, and CO data were collected while walking
      or moving by different private and public means of transport. Measurements were
      divided on the basis of different microenvironments (MEs), seasons, days of the
      week, and periods of the day. Data analysis shows statistically significant
      differences across MEs and monitoring periods. The highest measured median
      concentrations and data variability were observed for busy streets, walking or
      moving by motorized vehicle (CO, UFP) and in metro trains (PM); the lowest
      concentrations were observed in park areas and in indoor environments. The
      highest concentrations were measured during working day morning monitoring
      sessions. Regarding seasonal variation, UFP, PM, and CO showed different
      patterns: the highest median concentrations were observed in summer for CO, and
      in autumn and winter for the UFP and PM. Appreciable differences among all MEs
      and monitoring periods were observed: concentration patterns and variations
      appear related to typical sources of urban pollutants (traffic), proximity to
      sources, and time of day. [Supplementary materials are available for this
      article. Go to the publisher's online edition of Journal of Occupational and
      Environmental Hygiene for the following free supplemental resource: a file
      containing Table VI: Tau b (Kendall) index for non-parametric correlation tau
      test.]. 

PMID- 24116670
TI  - Lessons learned: Radiological protection for emergency workers at the TEPCO
      Fukushima Daiichi APP (part 1).
AB  - During the emergency work at the Fukushima Daiichi Atomic Power Plant (APP),
      Tokyo Electric Power Company (TEPCO) and the Japanese government experienced
      various problems in radiological exposure management for emergency workers. To
      improve the implementation of appropriate radiological protection, the Ministry
      of Health, Labour and Welfare (MHLW) issued a series of compulsory directives and
      provided administrative guidance to TEPCO. Based on the experiences and lessons
      learned, the MHLW recognized that to properly manage radiological exposure should
      a similar accident occur at another APP, sufficient measures and systematic
      preparation for radiological management should be ensured, including the
      following: a) Should an APP accident occur, assistance from the power company's
      corporate office or off-site support facilities outside the evacuation area is
      indispensable; b) Primary contractors must independently implement exposure
      management operations for the employees of their sub-contractors; c) APP
      operators should compile an operations manual, stockpile personal protective
      equipment, and personal alarm dosimeters (PADs) and prepare emergency systems and
      whole body counters (WBCs); and the labor standards authorities should compile an
      emergency operations manual. 

PMID- 24116672
TI  - Preschoolers selectively infer history when explaining outcomes: evidence from
      explanations of ownership, liking, and use.
AB  - Two experiments provide evidence that preschoolers selectively infer history when
      explaining outcomes and infer past events that could have plausibly happened. In
      Experiment 1, thirty-three 3-year-olds and thirty-six 4-year-olds explained why a
      character owns or likes certain objects. In Experiment 2, thirty-four 4-year-olds
      and thirty-six 5-year-olds explained why a character either owns or is using the
      objects. Children aged 4 and 5 years, but not 3 years, inferred history when
      explaining ownership, but not when explaining liking or use. They also tailored
      their explanations to reflect likelihood, allowing them to infer plausible past
      events. These findings are informative about the development of children's
      ability to infer history in their explanations and also suggest that preschoolers
      appreciate that ownership depends on past investment.

PMID- 24116673
TI  - Dynamics of serum-induced endothelial cell apoptosis in patients with myocardial
      infarction.
AB  - BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI)
      reperfused with primary coronary intervention (PCI), the dynamics of endothelial
      cell (EC) viability, apoptosis and necrosis and its relationship with the
      structural consequences on the left ventricle have not been addressed so far.
      DESIGN: In 20 STEMI patients, we incubated human umbilical vein endothelial cells
      (HUVECs) with serum drawn before reperfusion and subsequently afterwards (24, 96
      h, 30 days). Viability, apoptosis and necrosis percentages were evaluated by flow
      cytometry. Values were compared with 12 age- and sex-matched control subjects
      with normal coronary arteries. Cardiac magnetic resonance (CMR) was performed
      during the first week after infarction. RESULTS: Serum from STEMI patients
      induced a progressive loss of EC viability, with a nadir of 67.7 +/- 10.2% at 96
      h (baseline: 75 +/- 6% and controls: 80.2 +/- 3.9%, P < 0.001 in both cases).
      This is due to an increase in apoptosis that peaked at 96 h after reperfusion
      (15.2 +/- 7.1% vs. 11 +/- 6 at baseline and 5.8 +/- 1.6% in controls, P < 0.001
      in both cases). However, no significant dynamic changes in EC necrosis were
      detected. Extensive myocardial oedema (> 30%, median of left ventricular mass)
      was the only CMR variable significantly associated with a higher percentage of EC
      apoptosis at 96 h (extensive vs. nonextensive oedema: 18.3 +/- 6.8% vs. 12.1 +/-
      6.3%, P < 0.05). CONCLUSIONS: Dynamic changes in EC viability occur in the
      setting of STEMI patients reperfused with PCI, these changes peak late after
      reperfusion, they are mainly the result of an increase of apoptosis and are
      associated with the presence of extensive myocardial oedema.

PMID- 24116675
TI  - Cross-species infection trials reveal cryptic parasite varieties and a putative
      polymorphism shared among host species.
AB  - A parasite's host range can have important consequences for ecological and
      evolutionary processes but can be difficult to infer. Successful infection
      depends on the outcome of multiple steps and only some steps of the infection
      process may be critical in determining a parasites host range. To test this
      hypothesis, we investigated the host range of the bacterium Pasteuria ramosa, a
      Daphnia parasite, and determined the parasites success in different stages of the
      infection process. Multiple genotypes of Daphnia pulex, Daphnia longispina and
      Daphnia magna were tested with four Pasteuria genotypes using infection trials
      and an assay that determines the ability of the parasite to attach to the hosts
      esophagus. We find that attachment is not specific to host species but is
      specific to host genotype. This may suggest that alleles on the locus controlling
      attachment are shared among different host species that diverged 100 million
      year. However, in our trials, Pasteuria was never able to reproduce in nonnative
      host species, suggesting that Pasteuria infecting different host species are
      different varieties, each with a narrow host range. Our approach highlights the
      explanatory power of dissecting the steps of the infection process and resolves
      potentially conflicting reports on parasite host ranges. 

PMID- 24116674
TI  - Detailed computational study of the active site of the hepatitis C viral RNA
      polymerase to aid novel drug design.
AB  - The hepatitis C virus (HCV) RNA polymerase, NS5B, is a leading target for novel
      and selective HCV drug design. The enzyme has been the subject of intensive drug
      discovery aimed at developing direct acting antiviral (DAA) agents that inhibit
      its activity and hence prevent the virus from replicating its genome. In this
      study, we focus on one class of NS5B inhibitors, namely nucleos(t)ide mimetics.
      Forty-one distinct nucleotide structures have been modeled within the active site
      of NS5B for the six major HCV genotypes. Our comprehensive modeling protocol
      employed 287 different molecular dynamics simulations combined with the molecular
      mechanics/Poisson-Boltzmann surface area (MM-PBSA) methodology to rank and
      analyze these structures for all genotypes. The binding interactions of the
      individual compounds have been investigated and reduced to the atomic level. The
      present study significantly refines our understanding of the mode of action of
      NS5B-nucleotide-inhibitors, identifies the key structural elements necessary for
      their activity, and implements the tools for ranking the potential of additional
      much needed novel inhibitors of NS5B. 

PMID- 24116676
TI  - Volatile analysis and antimicrobial screening of the parasitic plant Cuscuta
      reflexa Roxb. from Nepal.
AB  - The essential oil from the parasitic vine Cuscuta reflexa Roxb., collected from
      Kirtipur, Kathmandu, Nepal, was obtained by hydrodistillation and analysed by gas
      chromatography-mass spectrometry. From a total of 62 peaks, 61 compounds were
      identified in the oil, accounting for 99.6% of the oil. The majority of the
      essential oil was dominated by the relatively rare component cis-3-butyl-4
      vinylcyclopentane (26.4%). The oil also contained substantial amounts of limonene
      (5.1%) and (E)-nerolidol (9.5%). Biological screening for antimicrobial
      activities did not show appreciable activity against either Gram-positive
      (Bacillus cereus and Staphylococcus aureus) or Gram-negative (Escherichia coli
      and Pseudomonas aeruginosa) bacteria. However, marginal activity against
      Aspergillus niger was observed (minimum inhibitory concentration = 313 MUg/mL).

PMID- 24116677
TI  - Surgical management and clinical outcomes of multiple-level symptomatic herniated
      thoracic discs.
AB  - OBJECT: Symptomatic herniated thoracic discs (HTDs) are rare, and patients
      infrequently require treatment of 2 or more disc levels. The authors assess the
      surgical management and outcomes of patients with multiple-level symptomatic
      HTDs. METHODS: A retrospective review of a prospectively maintained database was
      performed of 220 consecutive patients treated surgically for symptomatic HTDs.
      Clinical and surgical results were compared between patients with single-level
      disease and patients with multiple-level disease and also among the different
      approaches used for surgical decompression. RESULTS: Between 1992 and 2012, 56
      patients (mean age 48 years; 26 male, 30 female) underwent 62 procedures for 130
      HTDs. Forty-six patients (82%) had myelopathy, and 36 (64%) had thoracic
      radiculopathy; 24 patients had both conditions in varying degree. Symptom
      duration averaged 28 months. The surgical approach was dictated by disc size,
      consistency, and location. Twenty-three thoracotomy, 26 thoracoscopy, and 13
      posterolateral procedures were performed. Five patients required a combination of
      approaches. Patients underwent 2-level (n = 44), 3-level (n = 7), 4-level (n =
      4), or 5-level (n = 1) discectomies. Instrumented fusion was performed in 36
      patients (64%). Thirteen patients harbored 19 additional discs, which were deemed
      asymptomatic/nonoperative. The mean hospital stay was 6.5 days. Complete disc
      resection was verified with postoperative imaging in every patient. The
      procedural complication rate was 23%, and the nature of complications differed
      based on approach. No patients had surgery-related spinal cord injury or new
      myelopathy. At a mean follow-up of 48 months, myelopathy and radiculopathy had
      resolved or improved at a rate of 85% and 92%, respectively. Using a general
      linear model, preoperative symptom duration (p = 0.037) and perioperative
      hospital length of stay (p = 0.004) emerged as negative predictors of myelopathy
      improvement. Most patients (96%) were satisfied with the surgical results.
      Compared with 164 patients who underwent single-level HTD decompression, patients
      requiring surgery for multiple-level HTDs were more often myelopathic (p =
      0.012). Surgery for multiple-level HTDs was more likely to require a thoracotomy
      approach (p = 0.00055) and instrumented fusion (p < 0.0001) and resulted in
      greater blood loss (p = 0.0036) and higher complication rates (p = 0.0069). The
      rates of resolution for myelopathy (p = 0.24) and radiculopathy (p = 1.0),
      however, were similar between the 2 patient groups. CONCLUSIONS: The management
      of multiple-level symptomatic HTDs is complex, requiring individualized clinical
      decision making. The surgical approaches must be selected to minimize
      manipulation of the compressed thoracic spinal cord, and a patient may require a
      combination of approaches. Excellent surgical results can be achieved in this
      unique and challenging patient population.

PMID- 24116678
TI  - Sagittal plane analysis.

PMID- 24116679
TI  - Quality of life in adult intradural primary spinal tumors: 36-Item Short Form
      Health Survey correlation with McCormick and Aminoff-Logue scales.
AB  - OBJECT: The most appropriate method to determine the quality of life of patients
      with intradural primary spinal tumors (IPSTs) is not still well established.
      METHODS: Clinical data in 234 patients who underwent surgery for intradural
      spinal disease were collected prospectively. The 36-Item Short Form Health Survey
      (SF-36), a generic score scale, was administered to 148 patients with IPSTs to
      demonstrate if the survey can be used to effectively evaluate these patients.
      Forty-eight patients were excluded because they did not complete the protocol.
      The study was finally conducted with 100 patients (45 male and 55 female) with
      IPSTs, and the results were compared with those of 2 other scales: the McCormick
      scale and the Aminoff-Logue scale. RESULTS: Construct validity was demonstrated
      by confirming the hypothesized relationship between the scores of the SF-36 and
      the McCormick scale (p = 0.003), the Aminoff-Logue gait subscale (p = 0.025), the
      Aminoff-Logue micturition subscale (p = 0.013), and the Aminoff-Logue defecation
      subscale (p = 0.004). Reliability was demonstrated for all 8 SF-36 domain scales
      and the Physical Component Summary and the Mental Component Summary of the SF-36,
      where in each the Cronbach alpha satisfied the Nunnally criterion of > 0.85.
      CONCLUSIONS: The authors' results demonstrated that SF-36 provides valid and
      reliable data for patients with IPSTs and that the survey can be used
      appropriately to evaluate these patients.

PMID- 24116680
TI  - Anatomical location dictating major surgical complications for intradural
      extramedullary spinal tumors: a 10-year single-institutional experience.
AB  - OBJECT: Intradural extramedullary (IDEM) neoplasms are uncommon lesions that can
      pose a challenge for resection. Numerous factors affect the resectability and
      ultimately the outcome of these lesions. The authors report their 10-year
      institutional experience with the resection of IDEM neoplasms, focusing on the
      effect of location on surgical outcomes. METHODS: The authors performed a
      retrospective review of 96 consecutive patients who presented with a cervical
      and/or thoracic IDEM tumor that was resected between February 2000 and July 2009.
      All patients underwent MRI, and the axial location of the tumor was categorized
      as anterior, posterior, or lateral. Postoperative complications were assessed, as
      was neurological status at the patient's last follow-up clinic visit. Major
      complications assessed included CSF leakage requiring lumbar drainage,
      reexploration for epidural hematoma, and major postoperative neurological
      deficits. RESULTS: The mean +/- SD age at presentation was 51.16 +/- 17.87 years.
      Major surgical approach-related complications occurred in 15% of patients. Major
      non-approach related surgical complications occurred in 7.1% of patients, while
      minor complications occurred in 14.2% of patients. Postoperative neurological
      deficits occurred most commonly in the thoracic spine between T-1 and T-8. Based
      on axial spinal cord location, the surgery-related complications rates for all
      anterior tumors (n = 12) was 41.6%, whereas that for all lateral tumors (n = 69)
      was 4.4% and that for all posteriorly located tumors (n = 17) was 0%.
      CONCLUSIONS: Spinal IDEM tumors that are anteriorly located in the upper thoracic
      spine were found to have the highest rate of surgery-related complications and
      postoperative neurological deficits. This finding may be associated with the
      unforgiving anatomy of the upper thoracic spine in which there is a higher cord
      to-canal ratio and a tenuous vascular supply.

PMID- 24116681
TI  - Osteoporosis model.

PMID- 24116682
TI  - Intraarticular spacers.

PMID- 24116683
TI  - Intraarticular spacers.

PMID- 24116684
TI  - Genotoxicity of nimesulide in Wistar rats.
AB  - It is mandatory for all new drugs to be tested for their potential genotoxicity
      in addition to general toxicity testing. Some old drugs have not been tested
      adequately for their genotoxic effects because these were in use before the local
      regulations were enforced. According to the material safety database, the
      toxicological effect of nimesulide is not yet fully understood. The present study
      therefore aimed to explore the genotoxic potential of nimesulide in Wistar albino
      rats. Nimesulide at the dose level of 50 (Gr-50), 100 (Gr-100) and 200 (Gr-200)
      mg/kg body weight (b.w.) was given orally. Each rat in treated groups (Gr-50 to
      Gr-200; n = 10) and negative control group (Gr-NC; n = 10) were administered
      orally (p.o.) with nimesulide and normal saline, respectively, for 14 days.
      Similarly, rats of positive control (Gr-PC; n = 10) were administered with
      cyclophosphamide (CPA; 20 mg/kg b.w.) intraperitoneally. CPA served as positive
      control, whereas normal saline served as as negative control. Approximately 1-2
      mL of blood was collected from retro-orbital sinus for comet assay and
      subsequently rats were sacrificed to aspirate the femoral bone marrow for the
      micronucleus test. Structural chromosomal aberration, micronucleated
      polychromatic erythrocytes (MnPCEs), polychromatic erythrocytes (PCEs) and comet
      tail length were calculated using micronucleus assay and comet assay,
      respectively, which served as markers of genotoxicity. In the present study, it
      was observed that a significant increase in (1) different classified structural
      chromosomal aberrations with increase in nimesulide dose, such as gaps (50
      mg/kg), gaps, breaks and pulverizations (100 mg/kg) and gaps, breaks, fragments,
      rings and pulverizations (200 mg/kg) and (2) % MnPCE and comet tail length was
      observed in animals treated with CPA (p < 0.001) or 200 mg of nimesulide (p <
      0.05), as compared to negative control. In conclusion, nimesulide (200 mg/kg
      b.w.) produced a potential genotoxicity in rats.

PMID- 24116685
TI  - Molecular and electronic structures of six-coordinate "low-valent" [M((Me)bpy)3]0
      (M = Ti, V, Cr, Mo) and [M(tpy)2]0 (M = Ti, V, Cr), and seven-coordinate
      [MoF((Me)bpy)3](PF6) and [MX(tpy)2](PF6) (M = Mo, X = Cl and M = W, X = F).
AB  - The electronic structures of a series of so-called "low-valent" transition metal
      complexes [M((Me)bpy)3](0) and [M(tpy)2](0) ((Me)bpy = 4,4'-dimethyl-2,2'
      bipyridine and tpy = 2,2',6',2"-terpyridine) have been determined using a
      combination of X-ray crystallography, magnetochemistry, and UV-vis-NIR
      spectroscopy. More specifically, the crystal structures of the long-known
      complexes [Ti(IV)(tpy(2-))2](0) (S = 0, 6), [V(IV)(tpy(2-))2] (S = 1/2, 7),
      [Ti(III)((Me)bpy(*))3](0) (S = 0, 1), [V(II)((Me)bpy(*))2((Me)bpy(0))](0) (S =
      1/2, 2), and [Mo(III)((Me)bpy(*))3](0) (S = 0, 4) have been determined for the
      first time. In all cases, the experimental results confirm the electronic
      structure assignments that we ourselves have recently proposed. Additionally, the
      six-coordinate complex [Mo(III)(bpy(0))2Cl2]Cl.2.5CH3OH (S = 3/2, 13), and seven
      coordinate species [Mo(IV)F((Me)bpy(*))2((Me)bpy(0))](PF6) (S = 0, 5),
      [Mo(IV)Cl(tpy(*))2](PF6).CH2Cl2 (S = 0, 11), and [W(V)F(tpy(*))(tpy(2
      ))](PF6).CH2Cl2 (S = 0, 12) have been synthesized and, for the first time,
      crystallographically characterized. Using the resulting data, plus that from
      previously published high-resolution X-ray structures of analogous compounds, it
      is shown that there is a linear correlation between the average C(py)-C'(py) bond
      distances in these complexes and the total charge (n) of the ligands, {(bpy)3}(n)
      and {(tpy)2}(n). Hence, an assignment of the total charge of coordinated bpy or
      tpy ligands and, by extension, the oxidation state of the central metal ion can
      reliably be made on the basis of X-ray crystallography alone. In this study, the
      oxidation states of the metal ions range from +II to +V and in no case has an
      oxidation state of zero been validated. It is, therefore, highly misleading to
      use the term "low-valent" to describe any of the aforementioned neutral
      complexes.

PMID- 24116686
TI  - Estimation of the tissue damage after MI through time-frequency analysis of the
      electromechanical signals.
AB  - Abstract Coronary congestion is a heart disease that puts many lives at risk each
      year. The task of coronary arteries is to distribute blood to the heart tissue
      and any blockage in them can cause the tissue to absorb less oxygen and nutrients
      than needed (ischaemia disease). This imbalance will continue until the first
      cell is destroyed (myocardial infarction). Simulating the myocardial infarction
      in the laboratory rats, this study tries to determine the extent of tissue damage
      through the electrocardiogram (ECG) and atrial blood pressure (ABP) synchronic
      signals. The signals of 50 wistar rats with a weight range of 200-300 g were
      recorded at 30 min in the normal case and 30 min in the ischaemia and myocardial
      infarction (MI) case (the artificial complete blockage was in the left anterior
      descending coronary artery (LAD)). For a different injury in the rats' heart, the
      vasopressin (AVP) with different doses was injected to 40 rats. After that the
      images of the heart sections and the data were extracted, the 50-dimensional
      feature vector was generated by using the wavelet packet transform (WPT) on the
      ECG and ABP signals and also by obtaining the entropy of the wavelet
      coefficients. The extent of tissue damage on the images of the heart tissue was
      extracted by using the image processing method. Finally, the amount of the
      damaged tissue was estimated by four artificial neural networks (ANN) (with
      different structures) with an averaging criterion. The intelligent machine
      estimated the ischaemia and normal tissues with the average error of 2.91% for
      all the AVP doses and control cases.

PMID- 24116687
TI  - Repeated skin sampling and prolonged incubation period identified cutaneous
      Mycobacterium chelonae infection on the face in an immunocompetent man.

PMID- 24116688
TI  - Assessment of the cutaneous immune response during Arthroderma benhamiae and A.
      vanbreuseghemii infection using an experimental mouse model.
AB  - BACKGROUND: Dermatophytoses are common but poorly understood skin infections.
      Most in vivo studies have been performed using the guinea pig as the experimental
      animal model, which has several limitations. OBJECTIVES: To develop a mouse model
      of dermatophytosis suitable for multiple purposes, including the investigation of
      immunity against dermatophytes. MATERIALS AND METHODS: Two peculiar fungal
      species, Arthroderma benhamiae and A. vanbreuseghemii, isolated from tinea in
      humans having contact with rodents were used for epicutaneous inoculation. During
      the infection, clinical and histopathological follow-up were performed. The
      recruitment of immune cells was evaluated by immunofluorescence staining and the
      levels of cytokine mRNA were quantified by quantitative reverse transcriptase
      polymerase chain reaction in the skin of infected mice. RESULTS: The skin
      symptoms and microscopic lesions, including the colonization of keratinized
      epidermal and follicular structures by both dermatophytes, were highly similar to
      those observed in guinea pig infection models and in natural infections,
      mimicking acute superficial tinea in humans. The dermal inflammatory cellular
      infiltrate consisted of macrophages, dendritic cells and especially
      polymorphonuclear neutrophils, which are one of the histological 'clues' to the
      diagnosis of dermatophytosis. The in situ cytokine profile was characterized by
      the overexpression of transforming growth factor-beta, interleukin (IL)-1beta and
      IL-6 mRNA during infection, suggesting a role of the T-helper 17 pathway in the
      establishment of immunity. CONCLUSIONS: Our new reproducible and validated mouse
      model of dermatophytosis is a modern in vivo tool that allows a more in-depth
      understanding of the pathogenesis of human dermatophyte infections.

PMID- 24116690
TI  - Observing assembly of complex inorganic materials from polyoxometalate building
      blocks.
AB  - Understanding the aqueous state of discrete metal-oxo clusters, prenucleation
      clusters, and even simple ions is valuable for controlling the growth of metal
      oxide materials from water. Niobium polyoxometalates (Nb-POMs) are unique in the
      aqueous metal-oxo cluster landscape in their unusual solubility behavior:
      specifically, their solubility in water increases with increasing ion-pairing
      contact with their counterions, and thus provides a rare opportunity to observe
      these and related solution phenomena. Here, we isolate in the solid state the
      monomeric and dimeric building blocks, capped Keggin ions, of the extended Keggin
      chain materials that are now well-known: not only in Nb-POM chemistry, but Mo and
      V POM chemistry as well. Rb13[GeNb13O41].23H2O (Rb1), Cs10.6[H2.4GeNb13O41].27H2O
      (Cs1) and Cs18H6[(NbOH)SiNb12O40]2.38H2O (Cs2) were characterized by single
      crystal X-ray diffraction. Small angle X-ray scattering (SAXS) of solutions of
      Rb1 and Cs1 in varying conditions revealed oligomerization of the monomers into
      chain structures: the extent of oligomerization is controlled by pH,
      concentration, and the counterion. We distinctly observe chains of up to six
      Keggin ions in solution, with the large alkali cations for charge-balance. This
      combined solid state and solution study reveals in great detail the growth of a
      complex material from discrete monomeric building blocks. The fundamentals of the
      processes we are able to directly observe in this study, ion-association and
      hydrolysis leading to condensation, universally control the self-assembly and
      precipitation of materials from water. 

PMID- 24116689
TI  - Adverse drug events after hospital discharge in older adults: types, severity,
      and involvement of Beers Criteria Medications.
AB  - OBJECTIVES: To characterize adverse drug events (ADEs) occurring within the high
      risk 45-day period after hospitalization in older adults. DESIGN: Clinical
      pharmacists reviewed the ambulatory records of 1,000 consecutive discharges.
      SETTING: A large multispecialty group practice closely aligned with a
      Massachusetts-based health plan. PARTICIPANTS: Hospitalized individuals aged 65
      and older discharged home. MEASUREMENTS: Possible drug-related incidents
      occurring during the 45-day period after hospitalization were identified and
      presented to a pair of physician-reviewers who classified incidents as to whether
      an ADE was present, whether the event was preventable, and the severity of the
      event. Medications implicated in ADEs were further characterized according to
      their inclusion in the 2012 Beers Criteria for Potentially Inappropriate
      Medication Use in Older Adults. RESULTS: At least one ADE was identified during
      the 45-day period in 18.7% (n = 187) of the 1,000 discharges. Of the 242 ADEs
      identified, 35% (n = 84) were deemed preventable, of which 32% (n = 27) were
      characterized as serious, and 5% (n = 4) as life threatening. More than half of
      all ADEs occurred within the first 14 days after hospitalization. The percentage
      of ADEs in which Beers Criteria medications were implicated was 16.5% (n = 40).
      Beers criteria medications with both a high quality of evidence and strong
      strength of recommendation were implicated in 6.6% (n = 16) of the ADEs.
      CONCLUSION: ADEs are common and often preventable in older adults after hospital
      discharge, underscoring the need to address medication safety during this high
      risk period in this vulnerable population. Beers criteria medications played a
      small role in these events, suggesting that efforts to improve the quality and
      safety of medication use during this critical transition period must extend
      beyond a singular focus on Beers criteria medications.

PMID- 24116691
TI  - Trajectories of health-related quality of life in children with epilepsy: a
      cohort study.
AB  - PURPOSE: Little is known about subgroups of children with epilepsy who may
      experience less favorable outcomes over time. The objectives of this study were
      to document trajectories of health-related quality of life (HRQL) and to identify
      predictors of the trajectory group in children with new-onset epilepsy. METHODS:
      Data were obtained from the Health Related Quality of Life in Children with
      Epilepsy Study, a prospective multisite study of children 4-12 years old with new
      onset epilepsy followed for 24 months. Health-related quality of life was
      measured using the Quality of Life in Childhood Epilepsy questionnaire.
      Trajectories of HRQL were investigated using latent class trajectory modeling.
      Multinomial logistic regression was used to identify child, parent, and family
      predictors of HRQL trajectories. KEY FINDINGS: A total of 374 families responded
      at baseline and 283 (76%) completed the study. Five HRQL trajectories were
      observed: low-increasing (4%), moderate-decreasing (12%), moderate-increasing
      (22%), high-increasing (32%), and high-stable (30%). Many children in the low
      increasing, moderate-increasing, high-increasing, and high-stable had clinically
      meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In
      contrast, the majority of children in the moderate-decreasing group (56%)
      experienced clinically meaningful declines in their HRQL. Factors predicting
      trajectories were number of antiepileptic drugs prescribed, presence of comorbid
      behavior or cognitive problems, parent depression, and family functioning and
      demands. SIGNIFICANCE: Results suggested that children with epilepsy are not
      homogenous but rather consist of groups with different trajectories and unique
      predictors of HRQL. Problems associated with child behavior and cognition were
      the strongest predictors identified. Given that several risk factors are
      modifiable, it is important to examine these as potential targets within a family
      centered framework to improve HRQL of children with new-onset epilepsy.

PMID- 24116692
TI  - Malignant syphilis with ocular involvement in an immunocompetent patient.

PMID- 24116694
TI  - Copper/parylene core/shell nanowire surface fastener used for room-temperature
      electrical bonding.
AB  - The traditional bonding technology in electronic assembly relies on high
      temperature processes, such as reflow soldering or curing of adhesives, which
      result in undesired thermal excursions and residual stress at the bonding
      interface. Therefore, there is an urgent need to attach electronic components on
      the circuit board with good mechanical and electrical properties at room
      temperature. In this paper, a room-temperature electrical surface fastener
      consisting of copper/parylene core/shell nanowire (NW) arrays were prepared, and
      van der Waals (VDW) forces were utilized to interconnect the core/shell NWs.
      Interestingly, the Parylene C film becomes conductive due to dielectric breakdown
      when the thickness of it is miniaturized to nanoscale. Our electrical surface
      fastener exhibits high macroscopic adhesion strength (~25 N/cm(2)) and low
      electrical resistance (~4.22 * 10(-2) Omega.cm(2)). Meanwhile, a new theoretical
      model based on VDW forces between the NWs is proposed to explain the adhesion
      mechanism of the core/shell structure. 

PMID- 24116693
TI  - Prevalence and risk factors of cataract after chemotherapy with or without
      central nervous system irradiation for childhood acute lymphoblastic leukaemia:
      an LEA study.
AB  - Corticosteroid and central nervous system (CNS) irradiation can induce cataract
      in childhood lymphoblastic leukaemia survivors. Few prospective studies with
      systematic ophthalmological evaluation have been published. Cataract was
      prospectively assessed by serial slip lamp tests in 517 patients. All had acute
      lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS
      irradiation, and none had received haematopoietic stem cell transplantation.
      Median ages at last evaluation and follow-up duration from leukaemia diagnosis
      were 16.8 and 10.9 years, respectively. Cataract was observed in 21/517 patients
      (4.1%). Cumulative incidence was 4.5 +/- 1.2% at 15 years and reached 26 +/- 8.1%
      at 25 years. CNS irradiation was the only risk factor: prevalence was 11.1% in
      patients who had received irradiation and 2.8% in those who did not. We did not
      detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m(2) in
      patients with and without cataract, respectively. Cataract occurrence did not
      significantly impact quality of life. We conclude that, in the range of steroid
      dose reported here, the cataract risk proves very low 15 years after treatment
      without CNS irradiation but an even more prolonged follow-up is required because
      of potential very late occurrence. 

PMID- 24116695
TI  - Peri-Implant Strain in an In Vitro Model.
AB  - An in vitro experimental model was designed and tested to determine the influence
      that peri-implant strain may have on the overall crestal bone. Strain gages were
      attached to polymethylmethacrylate (PMMA) models containing a screw-type root
      form implant at sites 1 mm from the resin-implant interface. Three different
      types of crown superstructures (cemented, 1-screw [UCLA] and 2-screw abutment
      types) were tested. Loading (1 Hz, 200 N load) was performed using a MTS
      Mechanical Test System. The strain gage data were stored and organized in a
      computer for statistical treatment. Strains for all abutment types did not exceed
      the physiological range for modeling and remodeling of cancellous bone, 200-2500
      MUepsilon (microstrain). For approximately one-quarter of the trials, the strain
      values were less than 200 MUepsilon the zone for bone atrophy. The mean
      microstrain obtained was 517.7 MUepsilon. In conclusion, the peri-implant strain
      in this in vitro model did not exceed the physiologic range of bone remodeling
      under axial occlusal loading. 

PMID- 24116696
TI  - [Treponema pallidum subspecies pallidum -- the causative agent of neurosyphilis].
AB  - Neurosyphilis is defined as infection of central nervous system by Treponema
      pallidum subspecies pallidum. Neurosyphilis can develop at any stage after
      initial infec-tion and is reflected in laboratory results. The pathogenesis of
      neurosyphilis is similar to that of classical form of syphilis. Individuals with
      persistent abnormalities in the cerebrospinal fluid are at risk of the
      development of clinical manifestations. Proper understanding of particular forms
      of neurosyphilis for differential diagnosis is important to determine potential
      risk of the development of progressive disease in neurology.

PMID- 24116697
TI  - [Dengue fever cases in Czech workers returning from the Maldives].
AB  - AIM: The objective of this study is to present epidemiological characteristics
      and clinical symptoms of dengue fever cases in Czech workers who acquired the
      infection while working on the island of Fushivelavaru, Maldives. Furthermore,
      the study compares the sensitivity of novel direct detection assays, i.e. Real
      Time Polymerase Chain Reaction (RT-PCR) and detection of Dengue NS1 antigen.
      MATERIAL AND METHODS: The retrospective study evaluated the clinical course of
      dengue fever cases in Czech workers returning from a job in the Maldives who were
      diagnosed with dengue virus infection from September 1 to October 31, 2012. The
      laboratory diagnosis of dengue fever was based on the serological detection of
      IgM and IgG antibodies, detection of dengue NS1 antigen by enzyme-linked
      immunosobent assay (ELISA), and detection of dengue virus DNA by RT-PCR. RESULTS:
      The infection with dengue virus was confirmed in 18 males with a median age of 40
      years (IQR 36-47) who returned from a job in the Maldives. Only one patient
      required admission to the hospital while the others were treated on an outpatient
      basis. The most frequently observed symptoms were fever (18), headache (9),
      muscle and joint pain (8 and 7, respectively), and rash (9). Typical laboratory
      findings were leukocytopenia and thrombocytopenia, a low CRP level, and elevated
      aminotransferase activity. The clinical course was uncomplicated in all patients.
      The dengue NS1 antigen detection (positive in all 10 patients with acute dengue
      fever) showed significantly higher sensitivity than the detection of viral RNA
      using RT-PCR (positive in 4 patients), p = 0.011. CONCLUSION: Although the vast
      majority of dengue fever cases are diagnosed among travellers returning from the
      tropics, the presented study points out the risks posed by dengue fever to long
      term workers in endemic areas. The infection in the serologically naive hosts is
      usually uncomplicated; however, infected persons are at significant risk of
      developing a severe complicated clinical course if challenged by another
      serotype. Furthermore, sick leaves or premature departures cause a considerable
      economic burden to employers. In the diagnosis of acute dengue fever, preference
      should be given to highly sensitive and specific tests for the direct detection
      of dengue virus (NS1 antigen and RT-PCR assays).

PMID- 24116698
TI  - [Diagnosis of whooping cough by serology and real-time PCR].
AB  - The goal of this study is to summarize the results of the detection of Bordetella
      pertussis (BP) and Bordetella parapertussis (BPP) by a real-time polymerase chain
      reaction (RT-PCR) assay and serological methods. In 2008-2010, 73 patients of the
      Department of Clinical Immunology and Allergology of the Centre for Immunology
      and Microbiology, Public Health Institute in Usti nad Labem were screened for
      pertussis. They were selected according to the WHO and ECDC criteria, i. e. they
      presented with a persistent cough lasting more than two weeks. Direct detection
      of BP and BPP DNA from nasopharyngeal wash specimens was performed using a RT PCR
      assay. The serological responses were evaluated by a direct agglutination test
      for the detection of total antibodies and by enzyme-linked immunosobent assay
      (ELISA) for the detection of IgG, IgA, and IgM antibodies against pertussis
      toxin. Forty-two patients were positive for BP and/or BPP, 19 of them by RT-PCR
      (group A) and 23 by serology (group B). Ten group A patients (52.6%) were also
      positive by serology. Our results show that pertussis needs to be a consideration
      in persistent cough. We believe that increased awareness of the medical
      community, along with improved laboratory tests will result in increased
      detection of pertussis that is still considered by many physicians as a childhood
      infection.

PMID- 24116699
TI  - [Prevalence of selected congenital anomalies in the Czech Republic: renal and
      cardiac anomalies and congenital chromosomal aberrations].
AB  - STUDY GOAL: Analysis of the prevalence rates of selected diagnoses of congenital
      anomalies in the Czech Republic in 1994-2009. STUDY TYPE: Retrospective
      epidemiological analysis of postnatal and total (including prenatally diagnosed
      cases) prevalence of congenital anomalies from the database of the National
      Registry of Congenital Anomalies of the Czech Republic. MATERIAL AND METHODS:
      Data from the National Registry of Congenital Anomalies (NRCA) maintained by the
      Institute of Health Information and Statistics of the Czech Republic (IHIS CR)
      were used. Data on congenital anomalies in general and selected types of
      congenital anomalies were analyzed for the entire Czech Republic from 1994-2009.
      Additional data on prenatally diagnosed anomalies were obtained from medical
      genetics centres in the Czech Republic thanks to voluntary cooperation. This
      study analyzed postnatal and overall prevalence of congenital anomalies, with the
      latter including results of positive prenatal diagnosis. More detailed analysis
      was carried out for the following diagnoses: cystic kidney disease, renal
      agenesis/hypoplasia, tetralogy of Fallot, large vessel transposition, left heart
      hypoplasia, aortic coarctation, Down syndrome, Edward syndrome, and Patau
      syndrome. RESULTS: Cystic kidney disease showed a significant increase in 1999
      and 2000, mainly due to postnatally diagnosed cases. This can be explained, on
      the one hand, by the modification made to the reporting of congenital anomalies
      in the Czech Republic and, on the other hand, by an earlier and more complete
      detection of postnatal cases. Since 2000, there has been a significant increase
      in reported cystic kidney disease as a result of postnatal kidney screening. In
      1994-1999, the prevalence rates of this diagnosis ranged from 1.7 to 3.1 per
      10,000 live births. Similar trend is seen in the prevalence of renal
      agenesis/hypoplasia. In the monitored period, prenatally diagnosed cases showed a
      slight increase while postnatally diagnosed cases showed a considerable rise. In
      1994-1999, the prevalence rates of renal agenesis/hypoplasia ranged between 1.7
      and 3.0 per 10,000 live births and in 2000-2009, between 3.9 and 7.7 per 10,000
      live births. A major contributor to the upward trend is more frequent detection
      of unilateral renal agenesis/hypoplasia. The prevalence of tetralogy of Fallot
      remains nearly unchanged, with prenatally diagnosed cases accounting for more
      than 20% since 2000. The mean postnatal prevalence rate was 3.20 per 10,000 live
      births and the overall prevalence rate was 3.54 per 10,000 live births. A similar
      prevalence trend is seen in large vessel transposition. The mean postnatal
      prevalence rate was 3.01 per 10,000 live births and the mean overall prevalence
      rate was 3.38 per 10,000 live births. The proportion of prenatally diagnosed left
      heart hypoplasia showed a slow upward trend, reaching more than 75% in 2006. The
      mean postnatal prevalence rate was 1.44 per 10,000 live births and the mean
      overall prevalence rate was 2.86 per 10,000 live births. Aortic coarctation was
      diagnosed prenatally most often in 2003 (15.25%), with a mean of 7.5% for the
      whole period analyzed. Despite the prenatal diagnostic outcomes, the postnatal
      prevalence rates of left heart hypoplasia did not substantially vary in 1994
      2009. The mean postnatal prevalence rate was 4.87 per 10,000 live births and the
      mean overall prevalence rate was 5.26 per 10,000 live births. The prevalence
      rates of prenatally diagnosed Down syndrome were continuously increasing from
      4.79 to 17.73 per 10,000 live births and conversely, the postnatal prevalence
      rates were continuously decreasing from 7.79 to 3.31 per 10,000 live births.
      Increase in the overall prevalence rates can be explained mainly by the
      demographic situation in the Czech Republic in recent years: the average age at
      first birth and the first birth rate for women aged over 35 years were on the
      rise. The rate of prenatally diagnosed Down syndrome doubled from 40% to 80%.
      Similarly, the prevalence rate of prenatally diagnosed Edwards syndrome was on
      the rise while that of postnatally diagnosed cases was declining. The rate of
      prenatally diagnosed cases rose from 63% to 96% over the last two years. The mean
      prevalence rate of postnatally diagnosed cases was 0.72 per 10,000 live births
      and the mean overall prevalence rate was 3.78 per 10,000 live births. Similarly,
      the rate of prenatally diagnosed Patau syndrome increased from 30% in 1997 to
      100% in 2009 and the rate of postnatally diagnosed cases was declining. The mean
      prevalence rate of postnatally diagnosed cases was 0.40 per 10,000 live births
      and the mean overall prevalence rate was 1.38 per 10,000 live births. CONCLUSION:
      The overall prevalence rates of the monitored diagnoses from the group of
      congenital kidney disease (cystic kidney disease and renal agenesis/hypoplasia)
      were on the rise in the monitored -period mainly due to advances in imaging
      technologies (ultrasonography) and their use in both prenatal and postnatal
      diagnosis. Increase in postnatally diagnosed cases can be attributed primarily to
      the reporting of less severe cases (cystic kidney disease) or unilateral
      anomalies (renal agenesis and hypoplasia). As for the monitored congenital heart
      defects, advances in ultrasonographic imaging diagnosis played a considerable
      role in the increase of cases. The overall prevalence rate show a slow upward
      trend, but there is a significant decline in postnatally diagnosed cases due to
      prenatal diagnosis of a severe anomaly, left heart hypoplasia. As for congenital
      chromosomal aberrations, several interconnected factors influenced the final
      rate. Firstly, the proportion of prenatally diagnosed cases increases due to
      quantitative and qualitative improvements of the screening tests. They resulted
      in greater efficiency of prenatal diagnosis and, at the same time, in less need
      for invasive prenatal diagnostic procedures. Another factor is increase in
      average age at first birth and in the first birth rate for women aged over 35
      years resulting in higher overall prevalence rates of Down syndrome, Edwards
      syndrome, and Patau syndrome in the Czech Republic.

PMID- 24116700
TI  - HLA-B*58:45, a variant of HLA-B*58, found in a Taiwanese unrelated hematopoietic
      stem cell donor.

PMID- 24116701
TI  - Application of crystallization-induced asymmetric transformation to a general,
      scalable method for the resolution of 2,8-disubstituted Troger's base
      derivatives.
AB  - A general method for the gram scale resolution of 2-substituted and 2,8
      disubstituted Troger's base (TB) derivatives in 63-91% yield has been achieved
      through the application of crystallization-induced asymmetric transformation
      (CIAT). Enantiomeric ratios of the resolved TB derivatives range from 99.1:0.9 to
      >99.5:0.5. Among the Troger's base compounds resolved are four synthetically
      valuable bromo and iodo derivatives. 

PMID- 24116702
TI  - Ambient pressure laser desorption and laser-induced acoustic desorption ion
      mobility spectrometry detection of explosives.
AB  - The development of fast, mobile, and sensitive detection systems for security
      relevant substances is of enormous importance. Because of the low vapor pressures
      of explosives and improvised explosive devices, adequate sampling procedures are
      crucial. Ion mobility spectrometers (IMSs) are fast and sensitive instruments
      that are used as detection systems for explosives. Ambient pressure laser
      desorption (APLD) and ambient pressure laser-induced acoustic desorption (AP
      LIAD) are new tools suitable to evaporate explosives in order to detect them in
      the vapor phase. Indeed, the most important advantage of APLD or AP-LIAD is the
      capability to sample directly from the surface of interest without any transfer
      of the analyte to other surfaces such as wipe pads. A much more gentle
      desorption, compared to classical thermal-based desorption, is possible with
      laser-based desorption using very short laser pulses. With this approach the
      analyte molecules are evaporated in a very fast process, comparable to a shock
      wave. The thermal intake is reduced considerably. The functionality of APLD and
      AP-LIAD techniques combined with a hand-held IMS system is shown for a wide range
      of common explosives such as EGDN (ethylene glycol dinitrate), urea nitrate, PETN
      (pentaerythritol tetranitrate), HMTD (hexamethylene triperoxide diamine), RDX
      (hexogen), tetryl (2,4,6-trinitrophenylmethylnitramine), and TNT
      (trinitrotoluene). Detection limits down to the low nanogram range are obtained.
      The successful combination of IMS detection and APLD/AP-LIAD sampling is shown. 

PMID- 24116704
TI  - The genetic landscape of autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental
      disorders that show impaired communication and socialization, restricted
      interests, and stereotypical behavioral patterns. Recent advances in molecular
      medicine and high throughput screenings, such as array comparative genomic
      hybridization (CGH) and exome and whole genome sequencing, have revealed both
      novel insights and new questions about the nature of this spectrum of disorders.
      What has emerged is a better understanding about the genetic architecture of
      various genetic subtypes of ASD and correlations of genetic mutations with
      specific autism subtypes. Based on this new information, we outline a strategy
      for advancing diagnosis, prognosis, and counseling for patients and families. 

PMID- 24116705
TI  - 'You're HIV positive': perinatally infected young people's accounts of the
      critical moment of finding out their diagnosis.
AB  - This paper presents the recollections of 28 young people (15-24 years old) of
      formally learning that they had acquired HIV perinatally. Prior to the naming of
      their illness, many participants had experienced repeated biographical disruption
      through ill health and other major life events. However, the critical moment in
      their HIV trajectory was when they were told their diagnosis. How information
      about their diagnosis was managed previously, often disguised, combined with the
      ways in which the disclosure process was handled communicated to young people the
      inherent dangers and stigma associated with revealing their HIV status to others.
      The formal disclosure occasion also signalled to most participants the route of
      their HIV infection as well as previously hidden health information about family
      members. Although some young people discovered their diagnosis in an unplanned
      way, most described the disclosure of their HIV status as a structured event,
      usually a formal telling with those in authority naming the condition. This even
      applied to those for whom the discovery that they were HIV positive was a process
      that happened over time. This paper describes their memories of the disclosure
      event which for half took place over the age of 12. They received messages
      conveying the imperative to keep this information a secret to avoid being
      stigmatised and to protect themselves and their families. They described
      subsequent feelings of isolation and distress. Policy-makers and clinicians need
      to consider the WHO disclosure recommendations whilst taking into account
      individual circumstances. 

PMID- 24116703
TI  - Emerging role of interleukin-33 in autoimmune diseases.
AB  - Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It predominantly
      induces type 2 immune responses and thus is protective against atherosclerosis
      and nematode infections but contributes to allergic airway inflammation.
      Interleukin-33 also plays a pivotal role in the development of many autoimmune
      diseases through mechanisms that are still not fully understood. In this review,
      we focus on the recent advances in understanding of the expression and function
      of IL-33 in some autoimmune disorders, aiming to provide insight into its
      potential role in disease development. 

PMID- 24116706
TI  - Plasticity in adaptive immunity.

PMID- 24116707
TI  - Crosstalk between autophagy and apoptosis in RAW 264.7 macrophages infected with
      ectromelia orthopoxvirus.
AB  - Several studies have provided evidence that complex relationships between
      autophagic and apoptotic cell death pathways occur in cancer and virus-infected
      cells. Previously, we demonstrated that infection of macrophages with Moscow
      strain of ectromelia virus (ECTV-MOS) induces apoptosis under in vitro and in
      vivo conditions. Here, we found that autophagy was induced in RAW 264.7 cells
      during infection with ECTV-MOS. Silencing of beclin 1, an autophagy-related gene,
      reduced the percentage of late apoptotic cells in virus-infected RAW 264.7
      macrophages. Pharmacological modulation of autophagy by wortmannin (inhibitor) or
      rapamycin (inductor) did not affect or cause increased apoptosis in ECTV-MOS
      infected RAW 264.7 cells, respectively. Meantime, blocking apoptosis by a pan
      caspase inhibitor, Z-VAD-FMK, increased the formation of autophagosomes in
      infected macrophages. Taken together, three important points arise from our
      study. First, autophagy may co-occur with apoptosis in RAW 264.7 cells exposed to
      ECTV-MOS. Second, at later stages of infection, autophagy may partially
      participate in the execution of macrophage cell death by enhancing apoptosis.
      Third, when apoptosis is blocked infected macrophages undergo increased
      autophagy. Our results provide new information about the relationship between
      autophagy and apoptosis in ECTV-MOS-infected macrophages.

PMID- 24116708
TI  - Transcript analysis of P2X receptors in PBMCs of chronic HCV patients: an insight
      into antiviral treatment response and HCV-induced pathogenesis.
AB  - BACKGROUND: After invasion of hepatocytes and immune cells, hepatitis C virus has
      the ability to escape from the host immune system, leading to the progression of
      disease into chronic infection with associated liver morbidities. Adenosine
      5'triphosphate (ATP) is released in most of the pathological events from the
      affected cells and acts as a signaling molecule by binding to P2X receptors
      expressed on the host's immune cells and activates the immune system for pro
      inflammatory response. Therefore, the present study was designed to analyze the
      transcript expression of the ionotropic purinergic P2X receptors on peripheral
      blood mononuclear cells (PBMCs) of chronic HCV patients to have study the immune
      responses mediated by P2X receptors in chronic HCV infections. METHODS: PBMCs
      were isolated from the collected blood samples. Transcript analysis of P2X
      receptors in PBMCs was done. The identity of amplified product was confirmed by
      sequencing PCR, while the quantification of the transcript expression was done by
      real time PCR. The relative expression of the P2X receptors was analyzed by
      unpaired Student's t test using GraphPad Prims 5 software. RESULTS: We found that
      out of seven isoforms of P2X receptors, P2X1, P2X4, P2X5, and P2X7 receptors are
      expressed on the PBMCs. P2X1 and P2X7 are significantly upregulated in treatment
      naive chronic HCV patients by 2.2- and 2.5-fold, respectively. However, only P2X7
      expression is found increased by 2.7-fold in patients achieving sustained
      virological response (SVR) after antiviral treatment compared to healthy
      controls. The expression of P2X receptors remained unaltered in chronic HCV
      patients not responding to the treatment. CONCLUSION: The present study confirms
      the significant involvement of P2X receptors in the immune responses mediated by
      the PBMCs in the chronic HCV infection, which should be further investigated to
      devise strategies to augment the immune system against this chronic viral
      disease.

PMID- 24116709
TI  - Cellular reprogramming into a brown adipose tissue-like phenotype by co
      expression of HB-EGF and ADAM 12S.
AB  - Abnormal adipogenesis leads to excessive fat accumulation and several health
      disorders. Mouse fibroblasts (MLC) transfected with ADAM 12S and HB-EGF promoted
      lipid accumulation. Addition of KBR-7785, an ADAM 12S inhibitor, to HB-EGF/ADAM
      12S expressing cells suppressed adipogenesis. BrdU incorporation was attenuated
      and enhanced mitotracker staining was observed in HB-EGF/ADAM 12S cells.
      Quantitative real time RT-PCR resulted in elevated levels of expression of three
      brown adipose tissue (BAT) genes (PRDM16, PGC-1alpha, and UCP-1), while
      expression levels of the three white adipose tissue (WAT) genes (PPARgamma,
      C/EBPalpha, and AKT-1) were unaltered in HB-EGF/ADAM 12S cells. Amino- or carboxy
      terminal deletions of HB-EGF (HB-EGFDeltaN and HB-EGFDeltaC) co-expressed with
      ADAM 12S stimulated lipid accumulation. Human epidermoid carcinoma cells (A431)
      also exhibited lipid accumulation by HB-EGF/ADAM 12S co-expression. These studies
      suggest ADAM 12S and HB-EGF are involved in cellular plasticity resulting in the
      production of BAT-like cells and offers insight into novel therapeutic approaches
      for fighting obesity.

PMID- 24116710
TI  - Parent-child discrepancies in educational expectations: differential effects of
      actual versus perceived discrepancies.
AB  - This study explored how discrepancies between parents' and adolescents'
      educational expectations influenced adolescents' achievement using a nationally
      representative, longitudinal sample of 14,041 students (14 years old at
      baseline). Actual discrepancies (i.e., those between parents' and adolescents'
      actual educational expectations) and perceived discrepancies (i.e., those between
      adolescents' perceptions of their parents' educational expectations and
      adolescents' own) were examined. Achievement was higher when parents actually
      held higher expectations than adolescents held or when adolescents perceived that
      their parents' expectations were lower than their own. In contrast, achievement
      was lower when parents actually held lower expectations than adolescents held or
      when adolescents believed that their parents' expectations exceeded their own.
      Implications for identifying adolescents at risk and promoting adaptive parent
      child educational expectations are discussed.

PMID- 24116711
TI  - Revealing hidden dynamics within living soft matter.
AB  - In the study of living soft matter, we often seek to understand the mechanisms
      underlying the motion of a single molecule, an organelle, or some other tracer.
      The experimentally observed signature of the tracer is masked by its thermal
      fluctuations, inherent drift of the system, and instrument noise. In addition,
      the timing or length scales of the events of interest are often unknown. In the
      current issue of ACS Nano, Chen et al. present a general method for extracting
      the underlying dynamics from time series. Here, we provide an easily accessible
      introduction to the method, put it into perspective with the field, and exemplify
      how it can be used to answer important out-standing questions within soft matter
      and living systems. 

PMID- 24116712
TI  - Testing mitochondrial capture and deep coalescence in Amazonian cichlid fishes
      (Cichlidae: Cichla).
AB  - Hybridization and introgression have important consequences in evolution, such as
      increasing the genetic diversity and adaptive potential of a species. One of
      their most conspicuous footprints is discordance among gene trees or between
      genes and phenotypes. However, most studies that report introgression fail to
      disprove the null hypothesis that genetic incongruence may result from stochastic
      sorting of ancestral allelic polymorphisms. In the case of ancient introgression,
      these two processes may be especially difficult to distinguish topologically, but
      they make different predictions about the patterns of coalescence among loci.
      Here we apply three methods, molecular dating, multispecies coalescent models,
      and gene tree simulation under coalescence, to compare these two hypotheses that
      explain the polyphyletic mtDNA of the butterfly peacock bass, Cichla orinocensis.
      In comparison with a species tree based on 20 unlinked nuclear loci, we
      determined that mtDNA divergences were too recent to be explained by ancestral
      polymorphism. Similarly, coalescent species tree branches were significantly
      shorter when putative introgressed mtDNA was incorporated, and simulations showed
      the mtDNA topology to be unlikely under lineage sorting only. We conclude that
      introgression approximately 1.5 million years ago resulted in capture by C.
      orinocensis of an mtDNA lineage ancestral to the modern subspecies C. oc.
      monoculus. 

PMID- 24116714
TI  - Visually interpretable models of kinase selectivity related features derived from
      field-based proteochemometrics.
AB  - Achieving selectivity for small organic molecules toward biological targets is a
      main focus of drug discovery but has been proven difficult, for example, for
      kinases because of the high similarity of their ATP binding pockets. To support
      the design of more selective inhibitors with fewer side effects or with altered
      target profiles for improved efficacy, we developed a method combining ligand-
      and receptor-based information. Conventional QSAR models enable one to study the
      interactions of multiple ligands toward a single protein target, but in order to
      understand the interactions between multiple ligands and multiple proteins, we
      have used proteochemometrics, a multivariate statistics method that aims to
      combine and correlate both ligand and protein descriptions with affinity to
      receptors. The superimposed binding sites of 50 unique kinases were described by
      molecular interaction fields derived from knowledge-based potentials and
      Schrodinger's WaterMap software. Eighty ligands were described by Mold(2), Open
      Babel, and Volsurf descriptors. Partial least-squares regression including cross
      terms, which describe the selectivity, was used for model building. This
      combination of methods allows interpretation and easy visualization of the models
      within the context of ligand binding pockets, which can be translated readily
      into the design of novel inhibitors. 

PMID- 24116713
TI  - Contributing factors to disease outbreaks associated with untreated groundwater.
AB  - Disease outbreaks associated with drinking water drawn from untreated groundwater
      sources represent a substantial proportion (30.3%) of the 818 drinking water
      outbreaks reported to CDC's Waterborne Disease and Outbreak Surveillance System
      (WBDOSS) during 1971 to 2008. The objectives of this study were to identify
      underlying contributing factors, suggest improvements for data collection during
      outbreaks, and inform outbreak prevention efforts. Two researchers independently
      reviewed all qualifying outbreak reports (1971 to 2008), assigned contributing
      factors and abstracted additional information (e.g., cases, etiology, and water
      system attributes). The 248 outbreaks resulted in at least 23,478 cases of
      illness, 390 hospitalizations, and 13 deaths. The majority of outbreaks had an
      unidentified etiology (n = 135, 54.4%). When identified, the primary etiologies
      were hepatitis A virus (n = 21, 8.5%), Shigella spp. (n = 20, 8.1%), and Giardia
      intestinalis (n = 14, 5.7%). Among the 172 (69.4%) outbreaks with contributing
      factor data available, the leading contamination sources included human sewage (n
      = 57, 33.1%), animal contamination (n = 16, 9.3%), and contamination entering via
      the distribution system (n = 12, 7.0%). Groundwater contamination was most often
      facilitated by improper design, maintenance or location of the water source or
      nearby waste water disposal system (i.e., septic tank; n = 116, 67.4%). Other
      contributing factors included rapid pathogen transport through hydrogeologic
      formations (e.g., karst limestone; n = 45, 26.2%) and preceding heavy rainfall or
      flooding (n = 36, 20.9%). This analysis underscores the importance of identifying
      untreated groundwater system vulnerabilities through frequent inspection and
      routine maintenance, as recommended by protective regulations such as
      Environmental Protection Agency's (EPA's) Groundwater Rule, and the need for
      special consideration of the local hydrogeology. 

PMID- 24116715
TI  - Peri-implantational in vivo and in vitro embryo-trophoblast development after
      perigestational alcohol exposure in the CD-1 mouse.
AB  - Long-term pregestational ethanol exposure induced altered fertilization and
      preimplantation embryogenesis. We evaluated preimplantational embryo-trophoblast
      differentiation, growth and invasiveness after perigestational ethanol 10%
      ingestion for 15 days preceding and up to day 4 (treated females [TF]: TF-D4
      group) or 5 (TF-D5) of CD-1 gestation (control females [CF] with water). In TF
      D4, expanded and hatched blastocyst numbers were significantly reduced (p < 0.05)
      versus CF-D4. Abnormal embryos and percentage of pyknotic nuclei were increased,
      and early blastocyst growth (nuclear number/embryo) and mitotic index was reduced
      (p < 0.05) versus CF-D4. On day 5 of gestation, TF-D5 presented significantly
      reduced total embryos and advanced embryo type 3 number versus CF-D5 (p < 0.05).
      During in vitro development, up to 72-hour culture, TF-D5 had reduced embryo type
      1 (the least developed) and 3 percentages (p < 0.05) versus controls, whereas
      embryo type 2 percentage increased (p < 0.05) versus CF-D5. Embryo-trophoblast
      growth was studied during culture by morphometry. Embryo size ranges were
      classified as small, medium and large embryos. At 48-hour culture, small and
      medium embryos of TF had significantly increased mean area versus CF (p < 0.05),
      whereas large embryos had reduced mean area at 24-hour culture. Perigestational
      alcohol exposure up to days 4-5 induced embryo differentiation retardation,
      abnormal blastocyst growth and alterations of embryo-trophoblast growth and
      expansion during implantation, suggesting impaired regulation of trophoblast
      invasion and a relation with early pregnancy loss after mouse perigestational
      alcohol consumption.

PMID- 24116716
TI  - High expression of FOXP3 in primary melanoma is associated with tumour
      progression.
AB  - BACKGROUND: The antitumour immune response plays an important role in the
      prognosis of melanoma. High numbers of circulating regulatory T cells have been
      associated with rapid disease progression. OBJECTIVES: To assess the influence of
      forkhead box protein (FOXP)3, CD1a and langerin expression on the prognosis of
      primary melanoma. METHODS: We analysed 185 primary melanomas by
      immunohistochemical staining for expression of the regulatory T-cell marker FOXP3
      and the dendritic cell markers langerin and CD1a, and correlated marker
      expression with clinical outcome. RESULTS: Disease-free survival and overall
      survival were significantly longer in patients expressing low levels of FOXP3 in
      the primary melanoma, whereas they were associated with high expression of CD1a.
      The negative prognostic value of FOXP3 expression was independent of the Breslow
      tumour thickness. Langerin expression did not correlate with the clinical
      outcome. CONCLUSIONS: High expression of FOXP3 in the primary melanoma may be
      used as an additional independent prognostic marker for early tumour progression
      in patients with melanoma.

PMID- 24116717
TI  - Provider-to-provider communication in dermatology and implications of missing
      clinical information in skin biopsy requisition forms: a systematic review.
AB  - BACKGROUND: Various components of the skin biopsy requisition form (SBRF) may
      contribute to accurate dermatopathologic interpretation. METHODS: A search of
      electronic databases, including those of Ovid MEDLINE In-Process & Other Non
      Indexed Citations, Ovid MEDLINE, Ovid EMBASE, the Cochrane Database of Systematic
      Reviews, the Cochrane Central Register of Controlled Trials, and Scopus, was
      conducted from inception to October 2011. Two authors independently screened all
      articles for eligibility. Inclusion criteria required material to represent
      original studies on skin biopsy and pathology requisition forms. Data abstracted
      from each article that met the inclusion criteria included details of the study
      characteristics, including the study location, type of pathology practice,
      specimen type, type of dermatoses, medical specialty of the requesting provider,
      suggested clinical components, and format of the SBRF. RESULTS: Of 32 titles and
      abstracts reviewed, seven articles were included. From these, we determined that
      dermatologists, general practitioners and surgeons completed SBRFs. Commonly
      included components were patient demographics and requesting clinician
      characteristics. Clinical information and differential diagnosis were provided in
      4% (two of 48 surgeons) to 36% (18 of 50 dermatologists) of requisitions. Most
      SBRFs did not include information on specimen type, clinical morphology,
      photographs or clinical history. CONCLUSIONS: The limited medical literature
      demonstrates variation in the content of SBRFs across clinicians and practices,
      and suggests an important target for improvement in the quality of communication
      and dermatologic care by requesting clinicians and pathologists.

PMID- 24116718
TI  - Tolerance to COX-2 inhibitors in children with hypersensitivity to nonsteroidal
      anti-inflammatory drugs.
AB  - BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) can
      affect children, with the mechanism proposed being inhibition of the
      cyclooxygenase enzyme-1 (COX-1). In these patients nonchemically related NSAIDs,
      including COX-2 inhibitors, can induce the reaction, hampering treatment of fever
      and inflammatory processes. OBJECTIVES: To analyse retrospectively tolerance to
      etoricoxib, a selective COX-2 inhibitor, and to meloxicam, a preferential COX-2
      inhibitor, in children with hypersensitivity to NSAIDs. METHODS: Clinical records
      of children (aged 1-14 years) diagnosed with hypersensitivity reactions to NSAIDs
      from January 2006 to January 2013 were included. The diagnosis was confirmed by
      oral drug provocation test (DPT) with the culprit NSAIDs and acetylsalicylic acid
      (ASA). Tolerance to paracetamol, etoricoxib and meloxicam was also evaluated.
      RESULTS: The study included 41 children with a positive DPT with ASA and the
      culprit NSAID. DPT with paracetamol and etoricoxib was negative in all children,
      although two (4.9%) children developed a reaction after the administration of
      meloxicam. CONCLUSIONS: These data indicate that both etoricoxib and meloxicam
      are good alternatives for treatment in older children with hypersensitivity to
      NSAIDs.

PMID- 24116719
TI  - Craniectomy.

PMID- 24116720
TI  - Aggressive behavior.

PMID- 24116721
TI  - Improvement in clinical outcomes following optimal targeting of brain ventricular
      catheters with intraoperative imaging.
AB  - OBJECT: The accurate placement of cerebral ventricular shunt catheters in
      hydrocephalus is an important clinical problem. Malfunction of shunts remains
      their most common complication and greatest liability, and the influence of
      catheter position on shunt function remains poorly defined. The objectives of
      this study were as follows: 1) determine the accuracy of intraventricular
      catheter placement with respect to a historically favored target, defined as a 1
      cm radius sphere at the anterior lip of the ipsilateral foramen of Monro; 2)
      confirm that this target represents a satisfactory site for frontal and occipital
      catheter placement by examining whether inaccuracy is associated with more shunt
      failures; and 3) determine whether catheter trajectory, use of image
      confirmation, or other factors are associated with either the accuracy or the
      longevity of shunts. METHODS: A retrospective cohort analysis was conducted on
      236 patients with 426 ventricular shunts placed or revised at the University of
      Minnesota over a 10-year period. RESULTS: Accuracy of shunt placement was optimal
      in 43.9% of patients and suboptimal or poor in 56.1% of patients. Time to failure
      was significantly affected by the accuracy of catheter placement with respect to
      the ipsilateral foramen of Monro, with a 57% higher risk of failure with
      suboptimal placement (hazard ratio [HR] 1.57, 95% CI 1.26-1.96; p < 0.001) and a
      66% higher risk with poor placement (HR 1.66, 95% CI 1.45-1.89; p < 0.001)
      relative to optimal placement. The odds of highly suboptimal or unacceptable
      placement were significantly increased by lack of any intraoperative imaging (OR
      5.89, 95% CI 2.36-14.65; p < 0.001). Use of a nonfrontal posterior trajectory
      also showed a trend toward poor placement (OR 1.64, p = 0.138). CONCLUSIONS: The
      historical target for catheter tip placement within 1 cm of the foramen of Monro
      in the ipsilateral lateral ventricle was associated with significantly longer
      revision-free survival compared with other locations. This effect remained
      significant after adjusting for age and whether there was a prior history of
      shunting. The accuracy of catheter placement in both pediatric and adult patients
      was strongly associated with use of intraoperative fluoroscopic confirmation. In
      analyses comparing intraoperative fluoroscopy and no imaging, there was a non
      statistically significant difference in the 3-year time to failure, but the worst
      case scenario of catastrophic short-term failure was almost completely avoided
      with fluoroscopy. The authors conclude that accuracy of placement is critical for
      shunt survival, and that use of intraoperative imaging confirmation may optimize
      outcomes by avoiding the majority of unacceptable placements.

PMID- 24116722
TI  - Postoperative ischemic changes following brain metastasis resection as measured
      by diffusion-weighted magnetic resonance imaging.
AB  - OBJECT: Brain metastases occur in 10% to 40% of patients harboring cancer. In
      cases of neurosurgical metastasis resection, all postoperative neurological
      deterioration should be avoided. Reasons for postoperative deficits can be direct
      tissue damage due to resection, hemorrhage, venous congestive infarcts, or
      arterial ischemic events leading to tissue infarction. The aim of this study was
      to evaluate whether postoperative ischemic infarctions occur in surgery for brain
      metastasis and to determine their influence on new postoperative neurological
      deficits. METHODS: Patients who underwent resection of brain metastases and had
      preoperative and early postoperative (within 48 hours) MRI scans, including
      diffusion-weighted imaging sequences and apparent diffusion coefficient maps,
      between January 2009 and May 2012 were included in this study. Clinical and
      histopathological data (histopathological results, pre- and postoperative
      neurological status, and previous tumor-specific therapy) were recorded. RESULTS:
      One hundred twenty-two patients (56 male, 66 female) who underwent resection of
      brain metastases were included. The patients' mean age was 60 years (range 21-89
      years). The mean time span from initial tumor diagnosis to resection of brain
      metastasis was 44 months (range 0-338 months). The mean preoperative Karnofsky
      Performance Status was 80% (exact mean 76% +/- 17% [SD]), and the mean
      postoperative value was 80% (exact mean 78% +/- 17%). Twelve (9.8%) of the 122
      patients had postoperative permanent worsening of a neurological deficit or a new
      permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative
      ischemic lesions. When comparing patients with and without previous brain
      irradiation, 53.8% of patients with previous brain irradiation had ischemic
      lesions on postoperative imaging compared with 31.3% of patients without previous
      brain irradiation (p = 0.033). There was a significant association between
      ischemia and postoperative neurological status deterioration (transient or
      permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of
      their neurological status compared with 7 (9%) of the 78 patients who did not
      have ischemic lesions (p = 0.003). CONCLUSIONS: This study demonstrates a high
      prevalence of vascular incidents in patients undergoing resection for metastatic
      brain disease. Patients harboring postoperative ischemic lesions detected by MRI
      have a higher rate of neurological deficits (transient or permanent). Patients
      who had previous irradiation therapy are at higher risk of developing
      postoperative ischemic lesions. A large number of postoperative neurological
      deficits are caused by ischemic incidents.

PMID- 24116723
TI  - A randomized double-blind crossover trial comparing subthalamic and pallidal deep
      brain stimulation for dystonia.
AB  - OBJECT: The authors' aim was to compare the subthalamic nucleus (STN) with the
      globus pallidus internus (GPi) as a stimulation target for deep brain stimulation
      (DBS) for medically refractory dystonia. METHODS: In a prospective double-blind
      crossover study, electrodes were bilaterally implanted in the STN and GPi of 12
      patients with focal, multifocal, or generalized dystonia. Each patient was
      randomly selected to undergo initial bilateral stimulation of either the STN or
      the GPi for 6 months, followed by bilateral stimulation of the other nucleus for
      another 6 months. Preoperative and postoperative ratings were assessed by using
      the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and video recordings.
      Quality of life was evaluated by using questionnaires (36-item Short Form Health
      Survey). Supplemental Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
      scores were assessed for patients with focal dystonia (torticollis) by examining
      the video recordings. RESULTS: On average for all patients, DBS improved the
      BFMDRS movement scores (p < 0.05) and quality of life physical scores (p < 0.01).
      After stimulation of the STN, the mean 6-month improvement in BFMDRS movement
      score was 13.8 points; after stimulation of the GPi, this improvement was 9.1
      points (p = 0.08). Quality of life did not differ significantly regardless of
      which nucleus was stimulated. All 12 patients accepted 6 months of stimulation of
      the STN, but only 7 accepted 6 months of stimulation of the GPi. Among those who
      rejected stimulation of the GPi, 3 accepted concomitant stimulation of both the
      STN and GPi for 6 months, resulting in improved quality of life physical and
      mental scores and BFMDRS movement scores. Among the 4 patients who were rated
      according to TWSTRS, after 6 months of stimulation of both the STN and GPi,
      TWSTRS scores improved by 4.7% after stimulation of the GPi and 50.8% after
      stimulation of the STN (p = 0.08). CONCLUSIONS: The STN seems to be a well
      accepted, safe, and promising stimulation target in the treatment of dystonia,
      but further studies are necessary before the optimal target can be concluded.
      Simultaneous stimulation of the STN and GPi should be further investigated.
      Clinical trial registration no.: KF 01-110/01 (Committees on Biomedical Research
      Ethics of the Capital Region of Denmark).

PMID- 24116725
TI  - Prognostic relevance of global histone 3 lysine 9 acetylation in ependymal
      tumors.
AB  - OBJECT: Ependymal tumors are highly variable in clinical and molecular behavior
      and affect both children and adults. Regarding the paucity of appropriate
      experimental models, the underlying molecular mechanisms of their behavioral
      variability are poorly understood. Considering the increasing evidence of
      epigenetic changes in various tumors, in addition to the preclinical success of
      epigenetic-based therapeutics in tumors of the CNS, epigenetic study of ependymal
      tumors is warranted. METHODS: Using immunohistochemistry, the authors
      investigated the patterns of global acetylation of lysine position 9 of histone 3
      (H3K9Ac), an epigenetic marker of active gene transcription, in 85 ependymal
      tumors with various WHO grades and clinicopathological characteristics. RESULTS:
      Most of the nuclei in all ependymal tumors were H3K9Ac negative (mean +/- SD
      65.9% +/- 26.5 vs 34.1% +/- 26.5% positive, p < 0.0001). Subependymomas had more
      H3K9Ac-positive nuclei (67.2% +/- 10.2%) than myxopapillary ependymomas,
      ependymomas, and anaplastic ependymomas (p < 0.05). Additionally, intracranial
      parenchymal tumors had significantly fewer H3K9Ac-positive nuclei (13.1% +/-
      21.9%) than tumors of other CNS localizations (p < 0.001), and supratentorial
      ventricular tumors had the highest number of H3K9Ac-positive nuclei (66.4% +/-
      11.8%) among CNS ependymal tumors (p < 0.0001). The H3K9Ac pattern in ependymal
      tumors also revealed prognostic significance such that tumors with less than 20%
      acetylated nuclei had a higher probability of recurrence than tumors with 20% or
      more acetylated nuclei (p = 0.0327), and recurrent tumors had significantly fewer
      H3K9Ac-positive nuclei than primary ones (16% +/- 22.5% vs. 38% +/- 25.8%; p <
      0.0001). However, the effect of tumor location on survival of patients was
      nonsignificant in a multivariate survival analysis, and H3K9 acetylation levels
      of tumors contributed independently to the survival of patients. In addition,
      ependymal tumors with more than or equal to 20% H3K9 acetylated cells had lower
      MIB-1 expression than those with less than 20% H3K9 acetylated cells (p < 0.01).
      CONCLUSIONS: Global H3K9Ac contributes independently to the prognosis of patients
      with ependymal tumors such that tumors with lower H3K9Ac values have a higher
      probability of recurrence and are more proliferative. Additionally,
      subependymomas have a higher H3K9Ac profile than other ependymal tumor
      subclasses, underlining their benign clinical behavior.

PMID- 24116724
TI  - Development of the Mayo Investigational Neuromodulation Control System: toward a
      closed-loop electrochemical feedback system for deep brain stimulation.
AB  - OBJECT: Conventional deep brain stimulation (DBS) devices continue to rely on an
      open-loop system in which stimulation is independent of functional neural
      feedback. The authors previously proposed that as the foundation of a DBS "smart"
      device, a closed-loop system based on neurochemical feedback, may have the
      potential to improve therapeutic outcomes. Alterations in neurochemical release
      are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic
      voltammetry (FSCV) has been shown to be effective for recording these evoked
      neurochemical changes. However, the combination of FSCV with conventional DBS
      devices interferes with the recording and identification of the evoked analytes.
      To integrate neurochemical recording with neurostimulation, the authors developed
      the Mayo Investigational Neuromodulation Control System (MINCS), a novel,
      wirelessly controlled stimulation device designed to interface with FSCV
      performed by their previously described Wireless Instantaneous Neurochemical
      Concentration Sensing System (WINCS). METHODS: To test the functionality of these
      integrated devices, various frequencies of electrical stimulation were applied by
      MINCS to the medial forebrain bundle of the anesthetized rat, and striatal
      dopamine release was recorded by WINCS. The parameters for FSCV in the present
      study consisted of a pyramidal voltage waveform applied to the carbon-fiber
      microelectrode every 100 msec, ramping between -0.4 V and +1.5 V with respect to
      an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec.
      The carbon-fiber microelectrode was held at the baseline potential of -0.4 V
      between scans. RESULTS: By using MINCS in conjunction with WINCS coordinated
      through an optic fiber, the authors interleaved intervals of electrical
      stimulation with FSCV scans and thus obtained artifact-free wireless FSCV
      recordings. Electrical stimulation of the medial forebrain bundle in the
      anesthetized rat by MINCS elicited striatal dopamine release that was time-locked
      to stimulation and increased progressively with stimulation frequency.
      CONCLUSIONS: Here, the authors report a series of proof-of-principle tests in the
      rat brain demonstrating MINCS to be a reliable and flexible stimulation device
      that, when used in conjunction with WINCS, performs wirelessly controlled
      stimulation concurrent with artifact-free neurochemical recording. These findings
      suggest that the integration of neurochemical recording with neurostimulation may
      be a useful first step toward the development of a closed-loop DBS system for
      human application.

PMID- 24116726
TI  - Molecular mechanism of hearing loss.

PMID- 24116727
TI  - Misdirection and guidance of regenerating axons after experimental nerve injury
      and repair.
AB  - Misdirection of regenerating axons is one of the factors that can explain the
      limited results often found after nerve injury and repair. In the repair of mixed
      nerves innervating different distal targets (skin and muscle), misdirection may,
      for example, lead to motor axons projecting toward skin, and vice versa-that is,
      sensory axons projecting toward muscle. In the repair of motor nerves innervating
      different distal targets, misdirection may result in reinnervation of the wrong
      target muscle, which might function antagonistically. In sensory nerve repair,
      misdirection might give an increased perceptual territory. After median nerve
      repair, for example, this might lead to a dysfunctional hand. Different factors
      may be involved in the misdirection of regenerating axons, and there may be
      various mechanisms that can later correct for misdirection. In this review the
      authors discuss these different factors and mechanisms that act along the pathway
      of the regenerating axon. The authors review recently developed evaluation
      methods that can be used to investigate the accuracy of regeneration after nerve
      injury and repair (including the use of transgenic fluorescent mice, retrograde
      tracing techniques, and motion analysis). In addition, the authors discuss new
      strategies that can improve in vivo guidance of regenerating axons (including
      physical guidance with multichannel nerve tubes and biological guidance
      accomplished using gene therapy). 

PMID- 24116728
TI  - Radiographic resolution.

PMID- 24116729
TI  - Decompressive craniectomy for severe traumatic brain injury: is life worth
      living?
AB  - OBJECT: The object of this study was to assess the long-term outcome and quality
      of life of patients who have survived with severe disability following
      decompressive craniectomy for severe traumatic brain injury (TBI). METHODS: The
      authors assessed outcome beyond 3 years among a cohort of 39 patients who had
      been adjudged either severely disabled or in vegetative state 18 months after
      decompressive craniectomy for TBI. Assessments performed included the Extended
      Glasgow Outcome Scale, modified Barthel Index (mBI), Zarit Burden Interview, and
      36-Item Short-Form Health Survey (SF-36). The issue of retrospective consent for
      surgery was also assessed. RESULTS: Of the 39 eligible patients, 7 died, 12 were
      lost to follow-up, and 20 patients or their next of kin consented to participate
      in the study. Among those 20 patients, 5 in a vegetative state at 18 months
      remained so beyond 3 years, and the other 15 patients remained severely disabled
      after a median follow-up of 5 years. The patients' average daily activity per the
      mBI (Pearson correlation coefficient [r] = -0.661, p = 0.01) and SF-36 physical
      score (r = -0.543, p = 0.037) were inversely correlated with the severity of TBI.
      However, the SF-36 mental scores of the patients were reasonably high (median 46,
      interquartile range 37-52). The majority of patients and their next of kin
      believed that they would have provided consent for surgical decompression even if
      they had known the eventual outcome. CONCLUSIONS: Substantial physical recovery
      beyond 18 months after decompressive craniectomy for severe TBI was not observed;
      however, many patients appeared to have recalibrated their expectations regarding
      what they believed to be an acceptable quality of life.

PMID- 24116730
TI  - The influence of war on the development of neurosurgery.
AB  - The treatment of craniospinal war wounds proved to be a significant driving force
      in the early growth of neurosurgery as a specialty. This publication explores the
      historical relationship between the evolution of combat methodology from
      antiquity through modern conflicts as it dovetails with and drives corresponding
      advancements in the field of neurosurgery. Whether it's the basic management
      principles for intracranial projectile wounds derived from World War I
      experiences, the drastic improvement in the outcomes and management of spinal
      cord injuries observed in World War II, or the fact that both of these wars
      played a crucial role in the development of a training system that is the origin
      of modern residency programs, the influence of wartime experiences is pervasive. 

PMID- 24116731
TI  - Batch and flow photochemical benzannulations based on the reaction of ynamides
      and diazo ketones. Application to the synthesis of polycyclic aromatic and
      heteroaromatic compounds.
AB  - Highly substituted polycyclic aromatic and heteroaromatic compounds are produced
      via a two-stage tandem benzannulation/cyclization strategy. The initial
      benzannulation step proceeds via a pericyclic cascade mechanism triggered by
      thermal or photochemical Wolff rearrangement of a diazo ketone. The photochemical
      process can be performed using a continuous flow reactor which facilitates
      carrying out reactions on a large scale and minimizes the time required for
      photolysis. Carbomethoxy ynamides as well as more ketenophilic bis-silyl ynamines
      and N-sulfonyl and N-phosphoryl ynamides serve as the reaction partner in the
      benzannulation step. In the second stage of the strategy, RCM generates
      benzofused nitrogen heterocycles, and various heterocyclization processes furnish
      highly substituted and polycyclic indoles of types that were not available by
      using the previous cyclobutenone-based version of the tandem strategy. 

PMID- 24116732
TI  - Maternal obesity and induction of labor.
AB  - OBJECTIVE: To review induction of labor analyzed by body mass index (BMI)
      category in primigravidas and multigravidas. DESIGN: Prospective observational
      study. POPULATION: Women enrolled after sonographic confirmation of singleton
      pregnancy in the first trimester. SETTING: Large university teaching hospital.
      METHODS: Maternal height and weight were measured accurately before BMI
      calculation. Clinical details were recorded after review of individual obstetric
      records. MAIN OUTCOME MEASURES: Emergency cesarean section and obstetric
      interventions. RESULTS: Of 2000 women enrolled, 50.4% (n = 1008) were
      primigravidas and 17.3% (n = 346) were obese. The induction rate was 25.6% and
      the overall cesarean section rate 22.0%. Primigravidas were more likely to have
      labor induced than multigravidas (38.1% vs. 23.4%, p < 0.001). Compared with
      women with a normal BMI, obese primigravidas but not obese multigravidas were
      more likely to have labor induced. In primigravidas who had labor induced, the
      cesarean section rate was 20.6% (91/442) compared with 8.3% (17/206) in
      multigravidas who had labor induced (p < 0.001). In obese primigravidas,
      induction of labor was also more likely to be associated with other interventions
      such as epidural analgesia, fetal blood sampling and emergency cesarean section.
      In contrast, induction of labor in obese multigravidas was not only less common
      but also not associated with an increase in other interventions compared with
      multigravidas with a normal BMI. CONCLUSIONS: Due to the short-term and long-term
      implications of an unsuccessful induction in an obese primigravida, we recommend
      that induction of labor should only be undertaken for strict obstetric
      indications after careful consideration by an experienced clinician.

PMID- 24116733
TI  - Neuroimaging characteristics of MRI-negative orbitofrontal epilepsy with focus on
      voxel-based morphometric MRI postprocessing.
AB  - PURPOSE: The orbitofrontal (OF) region is one of the least explored regions of
      the cerebral cortex. There are few studies on patients with
      electrophysiologically and surgically confirmed OF epilepsy and a negative
      magnetic resonance imaging (MRI) study. We aimed to examine the neuroimaging
      characteristics of MRI-negative OF epilepsy with the focus on a voxel-based
      morphometric MRI postprocessing technique. METHODS: We included six patients with
      OF epilepsy, who met the following criteria: surgical resection of the OF lobe
      with/without adjacent cortex, seizure-free for >=12 months, invasive video
      electroencephalography (EEG) monitoring showing ictal onset from the OF area, and
      preoperative MRI regarded as negative. Patients were investigated in terms of
      their image postprocessing and functional neuroimaging characteristics,
      electroclinical characteristics obtained from noninvasive and invasive
      evaluations, and surgical pathology. MRI postprocessing on T1 -weighted high
      resolution scans was implemented with a morphometric analysis program (MAP) in
      MATLAB. KEY FINDINGS: Single MAP+ abnormalities were found in four patients;
      three were in the OF region and one in the ipsilateral mesial frontal area. These
      abnormalities were included in the resection. One patient had bilateral MAP+
      abnormalities in the OF region, with the ipsilateral one completely removed. The
      MAP+ foci were concordant with invasive electrophysiologic data in the majority
      of MAP+ patients (four of five). The localization value of 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) and ictal single-photon emission computed
      tomography (SPECT) is low in this cohort. Surgical pathology included focal
      cortical dysplasia, remote infarct, Rosenthal fiber formation and gliosis.
      SIGNIFICANCE: Our study highlights the importance of MRI postprocessing in the
      process of presurgical evaluation of patients with suspected orbitofrontal
      epilepsy and "normal" MRI. Using MAP, we were able to positively identify subtle
      focal abnormalities in the majority of the patients. MAP results need to be
      interpreted in the context of their electroclinical findings and can provide
      valuable targets in the process of planning invasive evaluation.

PMID- 24116735
TI  - The novel allele DRB1*07:23 was revealed by LABType HD DRB1 typing test and
      confirmed by sequence-based HLA typing.
AB  - The novel allele HLA-DRB1*07:23 shows a single nucleotide change in comparison to
      DRB1*07:01:01:01. 

PMID- 24116734
TI  - Enhanced photochemical hydrogen production by a molecular diiron catalyst
      incorporated into a metal-organic framework.
AB  - A molecular proton reduction catalyst [FeFe](dcbdt)(CO)6 (1, dcbdt = 1,4
      dicarboxylbenzene-2,3-dithiolate) with structural similarities to [FeFe]
      hydrogenase active sites has been incorporated into a highly robust Zr(IV)-based
      metal-organic framework (MOF) by postsynthetic exchange (PSE). The PSE protocol
      is crucial as direct solvothermal synthesis fails to produce the functionalized
      MOF. The molecular integrity of the organometallic site within the MOF is
      demonstrated by a variety of techniques, including X-ray absorption spectroscopy.
      In conjunction with [Ru(bpy)3](2+) as a photosensitizer and ascorbate as an
      electron donor, MOF-[FeFe](dcbdt)(CO)6 catalyzes photochemical hydrogen evolution
      in water at pH 5. The immobilized catalyst shows substantially improved initial
      rates and overall hydrogen production when compared to a reference system of
      complex 1 in solution. Improved catalytic performance is ascribed to structural
      stabilization of the complex when incorporated in the MOF as well as the
      protection of reduced catalysts 1(-) and 1(2-) from undesirable charge
      recombination with oxidized ascorbate. 

PMID- 24116736
TI  - Severe odontogenic infections: causes of spread and their management.
AB  - BACKGROUND: We conducted a study designed to investigate the clinical factors
      correlated with the spread of an odontogenic infection to the deep spaces of the
      head and neck. We also analyzed the treatment modalities for this and their
      outcomes. METHODS: The study retrospectively examined all patients admitted in
      2009 and 2010 to the General Hospital of Attica "KAT" with maxillofacial
      infections of odontogenic origin. The patients' case records were reviewed
      according to predefined inclusion and exclusion criteria and the relevant data
      were collected. The data were analyzed statistically. RESULTS: The study involved
      212 patients with a mean age of 40.8 y. Of these, 59.9% reported using oral
      antibiotics, usually (35.4%) without prescription. Moderate or poor oral hygiene
      was present in 78.3% of the study patients. The percentage of incompatible use of
      antibiotics due to non-compliance was 13.4%. Non-compliance indicates that these
      patients failed to follow the daily dosage or the dosing intervals of a
      prescribed antibiotic or they stopped an antibiotic due to an adverse reaction.
      Incision and drainage was required in 63.2% of the study patients, and 46.2%
      required extraction of the tooth responsible for their infection. A statistically
      significant association was documented between fever on admission and a prolonged
      hospital stay. No major complications were encountered among the study patients.
      CONCLUSIONS: Odontogenic infections remain a common cause of morbidity. Poor oral
      hygiene, self-medication, inadequate utilization of antibiotics, lack of
      treatment of the causative tooth, delayed presentation at the hospital, and
      bacterial resistance to empirically administered antibiotics appear to correlate
      with the spread of odontogenic infections. Incision and the evacuation of pus
      when indicated, intravenous antibiotic therapy, modification of the antibiotic
      regimen according to the results of sensitivity tests, and early treatment of the
      causative tooth constitute a successful management protocol for odontogenic
      infections.

PMID- 24116737
TI  - Thoracic gallstones: a delayed complication of laparoscopic cholecystectomy.
AB  - BACKGROUND: Thoracic complications resulting from gallstone spillage during
      laparoscopic cholecystectomy are rare and may occur years after the index
      surgery. We present the case of a chronic lung abscess resulting from trans
      diaphragmatic migration of gallstones spilled and "lost" during a laparoscopic
      cholecystectomy. METHODS: Case report and literature review. CASE REPORT: A 66
      year-old female who had undergone a laparoscopic cholecystectomy 5 y previously
      presented with hemoptysis and was found to have a chronic lung abscess caused by
      "lost" gallstones. Her symptoms resolved with video-assisted thorascopic surgery,
      pulmonary decortication, and wedge resection. CONCLUSIONS: Thoracic complications
      from "lost" gallstones following laparoscopic cholecystectomy include empyema,
      hemoptysis, and cholelithoptysis. These rare complications sometimes require
      surgery but not all presentations of thoracic gallstones mandate operative
      intervention. Because of these potential complications of "lost" gallstones,
      reasonable efforts should be made to retrieve gallstones spilled during
      cholecystectomy. Persistent pulmonary symptoms following laparoscopic
      cholecystectomy mandate further radiologic examination and a review of the
      patient's operative report for "lost" gallstones.

PMID- 24116738
TI  - Effects of age and diabetes mellitus on clinical outcomes in patients with
      peritoneal dialysis-related peritonitis.
AB  - BACKGROUND: Peritoneal dialysis (PD)-related peritonitis is the most common
      complication and the leading cause of technique failure for patients on PD
      therapy. The aim of this study was to review the episodes and outcomes of PD
      related peritonitis, with special reference to the effects of age and diabetes
      status. METHODS: The study comprised 204 consecutive peritonitis episodes between
      January 2001 and June 2011 from our registry database. Factors associated with
      treatment failure and mortality were analyzed with multi-variable logistic
      regression modeling. RESULTS: The overall peritonitis rate was one episode per 65
      patient-months or 0.187 episodes/patient-year. Older patients had lower
      probability of remaining free of peritonitis (log rank, p<0.001). Elderly
      patients and diabetic subjects had a higher risk of peritonitis-related dropout.
      Age (odds ratio [OR], 1.37; p=0.041), diabetes mellitus (OR, 3.64; p=0.005), and
      gram-negative peritonitis (OR, 3.55; p=0.011) were independent determinants of
      catheter removal. Age (OR, 1.93; p=0.026) and diabetes (OR, 5.98; p=0.015) were
      the only predictors of death from peritonitis. CONCLUSIONS: Old age and diabetes
      mellitus are two major risk factors for adverse outcomes of PD-related
      peritonitis. Although they are not contraindications to PD, our results suggest
      that these patients need meticulous care when peritonitis occurs.

PMID- 24116739
TI  - Methicillin-resistant Staphylococcus aureus in early ventilator-associated
      pneumonia: cause for concern?
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) accounts for almost 90% of
      infections in mechanically ventilated patients and more than one-quarter of all
      patients requiring intubation, with associated mortality rates as high as 70%.
      The rise in methicillin resistance within the community has led to a national
      increase in methicillin-resistant Staphylococcus aureus (MRSA) rates in early VAP
      and associated healthcare expenditure. METHODS: Trauma patients identified via an
      institutional VAP database were stratified by gender, age, severity of shock (24
      h transfusions), and severity of injury. The primary outcome measure was
      evaluation of the incidence and trend of early MRSA VAP over a 6-y period.
      Secondary outcomes examined the adequacy of our current empiric antibiotic
      regimen as it pertained to outcome variables, including mortality. RESULTS: A
      total of 997 episodes of VAP were identified in 727 patients. Linear regression
      showed that the incidence of early Staphylococcus aureus (SA) VAP was stable over
      the 6-y period (slope=-0.911; p=0.490). Over the same 6 y, however, the
      percentage of MRSA in early SA VAP (slope=3.95; p=0.0154) and the incidence of
      early MRSA VAP increased. No difference in mortality was detected between early
      methicillin-susceptible SA and early MRSA VAP. After adjustment for age, ISS, and
      24-h transfusion requirements, early MRSA was not an independent predictor of
      mortality (odds ratio [OR], 0.815; p=0.59). CONCLUSIONS: Although the incidence
      of early SA VAP with methicillin resistance increased significantly within the
      first 7 d of admission, this study showed no difference in mortality and resource
      utilization between early VAP from MRSA and other causative organisms, despite
      lack of empiric MRSA coverage.

PMID- 24116740
TI  - Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine
      endotoxemia.
AB  - BACKGROUND: The pathophysiologic features of acute respiratory distress syndrome
      (ARDS) are attributed to neutrophil accumulation and over-activation. Low blood
      immunoglobulin G concentrations in septic shock patients are associated with
      higher risk of developing ARDS. This study showed the effects of intravenous
      immunoglobulin (IVIg) on neutrophil apoptosis and accumulation in the lung during
      murine endotoxemia. METHODS: Male C57BL/6J mice were injected with saline or 7
      mg/kg of lipopolysaccharide (LPS), and 3 h later also were injected with saline,
      IVIg 300 mg/kg, or IVIg 1000 mg/kg intraperitoneally. At 12 h after LPS
      injection, mice were sacrificed and peripheral blood and lungs were collected.
      The lung messenger ribonucleic acid expression (tumor necrosis factor-alpha [TNF
      alpha], inducible nitric oxide synthase [iNOS], and intercellular adhesion
      molecule-1 [ICAM-1]) was determined using quantitative realtime reverse
      transcriptase-polymerase chain reaction. Lungs were immersed in 4%
      paraformaldehyde and then embedded in paraffin. Tissue slices were prepared and
      stained with naphthol AS-D chloroacetate esterase to detect neutrophils. The
      numbers of neutrophils (characterized by the segment number of their nuclei) were
      counted. Peripheral neutrophil apoptosis was detected by annexin V using flow
      cytometry and lung neutrophil apoptosis was detected by cleaved caspase-3 using
      immunohistochemistry. RESULTS: The survival rates of the saline group, LPS group,
      and IVIg group were all 100%. Apoptosis of peripheral blood neutrophils was
      inhibited by LPS. Neutrophil accumulation in the lung was decreased by both IVIg
      300 mg/kg and 1000 mg/kg. Segmented neutrophils were reduced by IVIg during
      endotoxemia. However, IVIg 300 mg/kg and 1000 mg/kg had no influence on the lung
      messenger ribonucleic acid expression of TNF-alpha, iNOS, or ICAM-1. Cleaved
      caspase-3-positive neutrophils were increased in the IVIg 300 mg/kg group during
      endotoxemia. The 1000 mg/kg IVIG dose reduced the number of segmented
      neutrophils, but did not induce cleaved-caspase 3-positive neutrophils.
      CONCLUSION: A therapeutic IVIg dose can attenuate neutrophil accumulation and
      regulate neutrophil apoptosis in the lung during endotoxemia. It is possible that
      the pathways by which IVIG induces neutrophil apoptosis may differ depending on
      the IVIg concentration.

PMID- 24116741
TI  - Is extended antibiotic prophylaxis necessary after penetrating trauma to the
      thoracolumbar spine with concomitant intraperitoneal injuries?
AB  - BACKGROUND: Prolonged courses of broad-spectrum antibiotics are often cited as
      standard care for the prevention of infectious complications in thoracolumbar or
      sacral (TLS) fractures following penetrating abdominal trauma. Perforation of a
      hollow viscus in addition to a TLS fracture is believed to be associated with a
      high incidence of spine infection. Because over use of antibiotics is associated
      with an increasing prevalence of multi-drug-resistant organisms, this study seeks
      to define the actual risk of infection of the spine and need for antibiotics in
      patients with TLS fractures and intraperitoneal injuries following penetrating
      trauma. METHODS: A retrospective review of 67 patients with penetrating abdominal
      trauma and concomitant TLS fracture was performed. Demographics, level of TLS
      fracture, associated spinal cord injury (SCI), need for operative intervention,
      presence of concomitant hollow viscus injury, and type and duration of antibiotic
      coverage were collected. In addition, associated infectious complications were
      reviewed. Spine infections were defined as spinal or paraspinal abscess,
      osteomyelitis of the spine, or meningitis. Intraabdominal infections were defined
      with imaging studies or positive peritoneal cultures. RESULTS: Sixty-seven
      patients (mean age of 27 +/- 9 years) had an exploratory laparotomy and one or
      more TLS fractures. Four patients died within 24 h and were excluded from further
      study. Thirty-eight patients (60%) had one or more hollow viscus injuries, 13
      (21%) had solid organ injuries alone and 12 (19%) had a non-therapeutic
      laparotomy. All patients received perioperative antibiotics; 92% received 48 h or
      less of antibiotic prophylaxis and 62% received only 24 h of antibiotics. In one
      patient with an isolated solid organ injury there was a spine infection (1%).
      CONCLUSIONS: In this study, 92% of patients received antibiotics for 48 h or less
      with no increased incidence of spine infections. Bacterial colonization of the
      vertebrae was not higher in patients with penetrating gastrointestinal injury.
      There is insufficient evidence to support the use of prolonged antibiotic
      prophylaxis to prevent spine infection in patients with penetrating abdominal
      trauma and TLS fracture.

PMID- 24116742
TI  - Necrotizing fasciitis of the perineum associated with a bartholin abscess.
AB  - BACKGROUND: Perineal gangrene was first described in healthy, young males more
      than two and one-half centuries ago. This disease, referred to commonly as
      Fournier gangrene, was marked by rapid progression, high mortality, and unknown
      etiology. In the last century the pathologic processes were described and
      accounts of perineal gangrene were reported in females. This disease still
      demonstrates a male predominance, but mortality does not demonstrate a gender
      predilection. CASE REPORT: We present a case of a Bartholin abscess progressing
      to necrotizing fasciitis of the perineum in a 53-year-old female following
      drainage and marsupialization. Perineal gangrene was treated successfully with
      serial debridements and a targeted antimicrobial regimen, with wound closure by
      secondary intention. RESULTS: Following retrospective case review, the exact
      pathophysiologic cause of progression to necrotizing fasciitis of the perineum is
      unclear though antibiotic resistance was a likely contributor. CONCLUSION:
      Clinical studies are necessary to investigate the differential incidence of this
      disease, which may result from diagnostic unawareness of necrotizing fasciitis of
      the perineum in females due to adherence to Fournier's original description or
      coding bias. Future clinical studies may define risk factors for disease better,
      and allow for standardized management and improved outcomes regardless of gender.

PMID- 24116743
TI  - PDGF and TGF-beta promote tenascin-C expression in subepithelial myofibroblasts
      and contribute to intestinal mucosal protection in mice.
AB  - BACKGROUND AND PURPOSE: Tenascin-C (TnC) is a multi-domain extracellular matrix
      glycoprotein that is expressed at a high level during embryogenesis but is almost
      absent during normal postnatal life. This multi-domain complex molecule is
      reported to associate with both pro-inflammatory and anti-inflammatory signalling
      cascades. In this study, we examined how TnC modulated intestinal inflammation.
      EXPERIMENTAL APPROACH: TnC pathophysiology was evaluated in cultures of rat
      intestinal subepithelial myofibroblasts (ISEMF) and intestinal epithelial cells.
      Wild-type and TnC(-/-) mice were treated with dextran sodium sulfate (DSS) to
      induce colitis. KEY RESULTS: DSS-induced colitis in mice markedly increased TnC
      in the damaged mucosal areas and up-regulated mRNA for TnC, pro-inflammatory
      cytokines and growth factors (PDGF-B and TGF-beta1). In addition, 2,4,6
      trinitrobenzene sulfonic acid-induced colitis and SAMP1/Yit mice, a model of
      spontaneous Crohn's disease, also exhibited increased mucosal TnC in colon and
      ilea respectively. PDGF receptor-alpha (PDGFRalpha) positive ISEMF were the
      primary TnC-producing cells in colon tissues. Accordingly, ISEMF collected from
      the rat colon constitutively expressed both TnC and PDGFRalpha. PDGF-BB and TGF
      beta1 up-regulated both TnC mRNA and protein levels in ISEMF. Knock-down of TnC
      gene increased susceptibility to DSS-induced colitis, compared with TnC(+/+)
      littermates. TnC(-/-) mice showed marked abrasion of intestinal mucosal barrier
      and increased inflammatory scores. Moreover, TnC accelerated both trans-well
      migration and wound healing in epithelial cells. CONCLUSIONS AND IMPLICATIONS:
      The pharmacological profiles of PDGF-BB and TGF-beta in colitis tissues and ISEMF
      suggest that increased TnC production during inflammation contributed to
      epithelial cell migration, remodelling and protection of intestinal barriers.

PMID- 24116744
TI  - Recognition of new citrulline-containing peptide epitopes by autoantibodies
      produced in vivo and in vitro by B cells of rheumatoid arthritis patients.
AB  - Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and
      specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes
      that may detect different subgroups of RA patients might have diagnostic and
      prognostic significance. We have investigated citrulline- and arginine-containing
      peptide pairs derived from filaggrin, collagen or vimentin, and compared this
      citrulline-peptide panel with the serological assays conventionally used to
      detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify
      antibody-secreting cells in in vitro cultures of RA B cells. Recognition of
      citrulline- and arginine-containing filaggrin, vimentin and collagen peptide
      epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide
      specific microarray. B cells were purified from blood by negative selection;
      antibody-producing cells were enumerated by ELISPOT assay. The panel composed of
      citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by
      RA sera with a sensitivity and specificity comparable with the currently used
      tests. Moreover, the combined citrulline-peptide panel including the new short
      epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA
      cases that were negative for antibodies against cyclic citrullinated peptides,
      mutated citrullinated vimentin or for rheumatoid factor. The results with the
      peptide-specific microarray have shown that although most ACPAs recognizing the
      four citrulline peptides are IgG, some of them specifically recognizing
      citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and
      so may be produced either by newly formed activated B cells or by unswitched B
      memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin
      detect ACPA-producing cells, and so could also be applied to study the B cells of
      RA patients.

PMID- 24116746
TI  - tert-Butyl hydroperoxide oxygenation of organic sulfides catalyzed by
      diruthenium(II,III) tetracarboxylates.
AB  - Diruthenium(II,III) carboxylates Ru2(esp)2Cl (1a), [Ru2(esp)2(H2O)2]BF4 (1b), and
      Ru2(OAc)4Cl (2) efficiently catalyze the oxygenation of organic sulfides. As
      noted in a previous work, 1a is active in oxygenation of organic sulfides with
      tert-butyl hydroperoxide (TBHP) in CH3CN. Reported herein in detail is the
      oxygenation activity of 1a, 1b, and 2, with the latter being highly selective in
      oxo-transfer to organic sulfides using TBHP under ambient conditions. Solvent
      free oxidation reactions were achieved through dissolving 1a or 1b directly into
      the substrate with 2 equiv of TBHP, yielding TOF up to 2056 h(-1) with 1b. Also
      examined are the rate dependence on both catalyst and oxidant concentration for
      reactions with catalysts 1a and 2. Ru2(OAc)4Cl may be kinetically saturated with
      TBHP; however, Ru2(esp)2Cl does not display saturation kinetics. By use of a
      series of para-substituted thioanisoles, linear free-energy relationships were
      established for both 1a and 2, where the reactivity constants (rho) are negative
      and that of 1a is about half that of 2. Given these reactivity data, two
      plausible reaction pathways were suggested. Density functional theory (DFT)
      calculation for the model compound Ru2(OAc)4Cl.TBHP, with TBHP on the open axial
      site, revealed elongation of the O-O bond of TBHP upon coordination. 

PMID- 24116745
TI  - Comprehensive analysis of protein digestion using six trypsins reveals the origin
      of trypsin as a significant source of variability in proteomics.
AB  - Trypsin is an endoprotease commonly used for sample preparation in proteomics
      experiments. Importantly, protein digestion is dependent on multiple factors,
      including the trypsin origin and digestion conditions. In-depth characterization
      of trypsin activity could lead to improved reliability of peptide detection and
      quantitation in both targeted and discovery proteomics studies. To this end, we
      assembled a data analysis pipeline and suite of visualization tools for quality
      control and comprehensive characterization of preanalytical variability in
      proteomics experiments. Using these tools, we evaluated six available proteomics
      grade trypsins and their digestion of a single purified protein, human serum
      albumin (HSA). HSA was aliquoted and then digested for 2 or 18 h for each
      trypsin, and the resulting digests were desalted and analyzed in triplicate by
      reversed-phase liquid chromatography-tandem mass spectrometry. Peptides were
      identified and quantified using the NIST MSQC pipeline and a comprehensive HSA
      mass spectral library. We performed a statistical analysis of peptide abundances
      from different digests and further visualized the data using the principal
      component analysis and quantitative protein "sequence maps". While the
      performance of individual trypsins across repeat digests was reproducible,
      significant differences were observed depending on the origin of the trypsin
      (i.e., bovine vs porcine). Bovine trypsins produced a higher number of peptides
      containing missed cleavages, whereas porcine trypsins produced more semitryptic
      peptides. In addition, many cleavage sites showed variable digestion kinetics
      patterns, evident from the comparison of peptide abundances in 2 h vs 18 h
      digests. Overall, this work illustrates effects of an often neglected source of
      variability in proteomics experiments: the origin of the trypsin. 

PMID- 24116749
TI  - Wilson ratio of fermi gases in one dimension.
AB  - We calculate the Wilson ratio of the one-dimensional Fermi gas with spin
      imbalance. The Wilson ratio of attractively interacting fermions is solely
      determined by the density stiffness and sound velocity of pairs and of excess
      fermions for the two-component Tomonaga-Luttinger liquid phase. The ratio
      exhibits anomalous enhancement at the two critical points due to the sudden
      change in the density of states. Despite a breakdown of the quasiparticle
      description in one dimension, two important features of the Fermi liquid are
      retained; namely, the specific heat is linearly proportional to temperature,
      whereas the susceptibility is independent of temperature. In contrast to the
      phenomenological Tomonaga-Luttinger liquid parameter, the Wilson ratio provides a
      powerful parameter for testing universal quantum liquids of interacting fermions
      in one, two, and three dimensions. 

PMID- 24116747
TI  - A randomised prospective trial of intra-operative oesophageal Doppler-guided
      fluid administration in major gynaecological surgery.
AB  - Intra-operative oesophageal Doppler monitor-guided fluid management has been
      associated with improved postoperative length of hospital stay and morbidity in
      gastrointestinal and orthopaedic surgery. We designed a randomised controlled
      trial to test the hypothesis that this approach to intra-operative fluid
      management in major elective open gynaecological surgery would shorten the length
      of postoperative stay, defined as time to readiness for hospital discharge.
      Postoperative morbidity was evaluated as a secondary outcome. The oesophageal
      Doppler monitor group underwent intra-operative fluid management using an
      oesophageal Doppler-guided stroke volume optimisation algorithm. Control group
      (conventional fluid therapy) intra-operative fluid management was based on
      conventional haemodynamic indices. In a single centre, 102 patients were randomly
      assigned: 51 to the oesophageal Doppler monitor group (51 analysed) and 51 to the
      control group (50 analysed). Evaluators who were blinded to patient assignment
      collected postoperative outcome data. There was no difference in the length of
      postoperative hospital stay between the groups: median (IQR [range]) number of
      days until ready for discharge was 6 (5-8 [4-25]) days in the oesophageal Doppler
      monitor group compared with 7 (5-9 [4-42]) days in the control group, p = 0.5.
      There was no difference between the groups in postoperative morbidity survey
      scores on postoperative days 1, 3 or 5. Seven patients in the oesophageal Doppler
      monitor group and 11 in the control group experienced postoperative complications
      (p = 0.41). These findings question whether intra-operative oesophageal Doppler
      guided fluid therapy is of benefit in patients undergoing open gynaecological
      surgery.

PMID- 24116748
TI  - The effects of adapted tango on spatial cognition and disease severity in
      Parkinson's disease.
AB  - The authors determined effects of community-based adapted tango on spatial
      cognition and disease severity in Parkinson's disease (PD) while controlling for
      the effects of social interaction. Thirty-three individuals with mild-to-moderate
      PD (stage I-III) were assigned to twenty 90-min tango (n = 24) or education (n =
      9) lessons over 12 weeks. Disease severity, spatial cognition, balance, and fall
      incidence were evaluated pre-, post-, and 10-12 weeks postintervention. The
      authors evaluated differences using t tests and analyses of variance. Twenty
      three tango and 8 education participants finished. Tango participants improved on
      disease severity (p = .008), and spatial cognition (p = .021) compared with
      education participants. Tango participants also improved in balance (p = .038),
      and executive function (p = .012). Gains were maintained 10-12 weeks
      postintervention. Multimodal exercise with structured syllabi may improve disease
      severity and spatial cognition in PD.

PMID- 24116750
TI  - Entanglement of interacting fermions in quantum Monte Carlo calculations.
AB  - Given a specific interacting quantum Hamiltonian in a general spatial dimension,
      can one access its entanglement properties, such as the entanglement entropy
      corresponding to the ground state wave function? Even though progress has been
      made in addressing this question for interacting bosons and quantum spins, as yet
      there exist no corresponding methods for interacting fermions. Here we show that
      the entanglement structure of interacting fermionic Hamiltonians has a
      particularly simple form-the interacting reduced density matrix can be written as
      a sum of operators that describe free fermions. This decomposition allows one to
      calculate the Renyi entropies for Hamiltonians which can be simulated via
      determinantal quantum Monte Carlo calculations, while employing the efficient
      techniques hitherto available only for free fermions. The method presented works
      for the ground state, as well as for the thermally averaged reduced density
      matrix. 

PMID- 24116751
TI  - Hidden-symmetry-protected topological semimetals on a square lattice.
AB  - We study a two-dimensional fermionic square lattice, which supports the existence
      of a two-dimensional Weyl semimetal, quantum anomalous Hall effect, and 2pi-flux
      topological semimetal in different parameter ranges. We show that the band
      degenerate points of the two-dimensional Weyl semimetal and 2pi-flux topological
      semimetal are protected by two distinct novel hidden symmetries, which both
      correspond to antiunitary composite operations. When these hidden symmetries are
      broken, a gap opens between the conduction and valence bands, turning the system
      into a insulator. With appropriate parameters, a quantum anomalous Hall effect
      emerges. The degenerate point at the boundary between the quantum anomalous Hall
      insulator and trivial band insulator is also protected by the hidden symmetry. 

PMID- 24116752
TI  - Universality of the momentum band density of periodic networks.
AB  - The momentum spectrum of a periodic network (quantum graph) has a band-gap
      structure. We investigate the relative density of the bands or, equivalently, the
      probability that a randomly chosen momentum belongs to the spectrum of the
      periodic network. We show that this probability exhibits universal properties.
      More precisely, the probability to be in the spectrum does not depend on the edge
      lengths (as long as they are generic) and is also invariant within some classes
      of graph topologies. 

PMID- 24116753
TI  - Exact classification of Landau-Majorana-Stuckelberg-Zener resonances by floquet
      determinants.
AB  - Recent experiments have shown that Landau-Majorana-Stuckelberg-Zener (LMSZ)
      interferometry is a powerful tool for demonstrating and exploiting quantum
      coherence not only in atomic systems but also in a variety of solid state quantum
      systems such as spins in quantum dots, superconducting qubits, and nitrogen
      vacancy centers in diamond. In this Letter, we propose and develop a general
      (and, in principle, exact) theoretical formalism to identify and characterize the
      interference resonances that are the hallmark of LMSZ interferometry. Unlike
      earlier approaches, our scheme does not require any approximations, allowing us
      to uncover important and previously unknown features of the resonance structure.
      We also discuss the experimental observability of our results. 

PMID- 24116754
TI  - Detection-loophole-free test of quantum nonlocality, and applications.
AB  - We present a source of entangled photons that violates a Bell inequality free of
      the "fair-sampling" assumption, by over 7 standard deviations. This violation is
      the first reported experiment with photons to close the detection loophole, and
      we demonstrate enough "efficiency" overhead to eventually perform a fully
      loophole-free test of local realism. The entanglement quality is verified by
      maximally violating additional Bell tests, testing the upper limit of quantum
      correlations. Finally, we use the source to generate "device-independent" private
      quantum random numbers at rates over 4 orders of magnitude beyond previous
      experiments. 

PMID- 24116755
TI  - Entanglement concentration is irreversible.
AB  - In quantum information theory, it is widely believed that entanglement
      concentration for bipartite pure states is asymptotically reversible. In order to
      examine this, we give a precise formulation of the problem, and show a trade-off
      relation between performance and reversibility, which implies the irreversibility
      of entanglement concentration. Then, we regard entanglement concentration as
      entangled state compression in an entanglement storage with lower dimension.
      Because of the irreversibility of entanglement concentration, an initial state
      cannot be completely recovered after the compression process and a loss
      inevitably arises in the process. We numerically calculate this loss and also
      derive for it a highly accurate analytical approximation. 

PMID- 24116756
TI  - Dynamics of thermalization and decoherence of a nanoscale system.
AB  - We study the decoherence and thermalization dynamics of a nanoscale system
      coupled nonperturbatively to a fully quantum-mechanical bath. The system is
      prepared out of equilibrium in a pure state of the complete system. We propose a
      random matrix model and show analytically that there are two robust temporal
      regimes in the approach of the system to equilibrium-an initial Gaussian decay
      followed by an exponential tail, consistent with numerical results on small
      interacting lattices [S. Genway, A. F. Ho, and D. K. K. Lee, Phys. Rev. Lett.
      105, 260402 (2010)]. Furthermore, the system decays towards a Gibbs ensemble in
      accordance with the eigenstate thermalization hypothesis. 

PMID- 24116757
TI  - Real-world two-photon interference and proof-of-principle quantum key
      distribution immune to detector attacks.
AB  - Several vulnerabilities of single-photon detectors have recently been exploited
      to compromise the security of quantum-key-distribution (QKD) systems. In this
      Letter, we report the first proof-of-principle implementation of a new quantum
      key-distribution protocol that is immune to any such attack. More precisely, we
      demonstrated this new approach to QKD in the laboratory over more than 80 km of
      spooled fiber, as well as across different locations within the city of Calgary.
      The robustness of our fiber-based implementation, together with the enhanced
      level of security offered by the protocol, confirms QKD as a realistic technology
      for safeguarding secrets in transmission. Furthermore, our demonstration
      establishes the feasibility of controlled two-photon interference in a real-world
      environment and thereby removes a remaining obstacle to realizing future
      applications of quantum communication, such as quantum repeaters and, more
      generally, quantum networks. 

PMID- 24116758
TI  - Experimental measurement-device-independent quantum key distribution.
AB  - Quantum key distribution is proven to offer unconditional security in
      communication between two remote users with ideal source and detection.
      Unfortunately, ideal devices never exist in practice and device imperfections
      have become the targets of various attacks. By developing up-conversion single
      photon detectors with high efficiency and low noise, we faithfully demonstrate
      the measurement-device-independent quantum-key-distribution protocol, which is
      immune to all hacking strategies on detection. Meanwhile, we employ the decoy
      state method to defend attacks on a nonideal source. By assuming a trusted source
      scenario, our practical system, which generates more than a 25 kbit secure key
      over a 50 km fiber link, serves as a stepping stone in the quest for
      unconditionally secure communications with realistic devices. 

PMID- 24116759
TI  - General rules for bosonic bunching in multimode interferometers.
AB  - We perform a comprehensive set of experiments that characterize bosonic bunching
      of up to three photons in interferometers of up to 16 modes. Our experiments
      verify two rules that govern bosonic bunching. The first rule, obtained recently,
      predicts the average behavior of the bunching probability and is known as the
      bosonic birthday paradox. The second rule is new and establishes a n!-factor
      quantum enhancement for the probability that all n bosons bunch in a single
      output mode, with respect to the case of distinguishable bosons. In addition to
      its fundamental importance in phenomena such as Bose-Einstein condensation,
      bosonic bunching can be exploited in applications such as linear optical quantum
      computing and quantum-enhanced metrology. 

PMID- 24116760
TI  - Solovay-Kitaev decomposition strategy for single-qubit channels.
AB  - Inspired by the Solovay-Kitaev decomposition for approximating unitary operations
      as a sequence of operations selected from a universal quantum computing gate set,
      we introduce a method for approximating any single-qubit channel using single
      qubit gates and the controlled-not (cnot). Our approach uses the decomposition of
      the single-qubit channel into a convex combination of "quasiextreme" channels.
      Previous techniques for simulating general single-qubit channels would require as
      many as 20 cnot gates, whereas ours only needs one, bringing it within the range
      of current experiments. 

PMID- 24116761
TI  - Experimental determination of Ramsey numbers.
AB  - Ramsey theory is a highly active research area in mathematics that studies the
      emergence of order in large disordered structures. Ramsey numbers mark the
      threshold at which order first appears and are extremely difficult to calculate
      due to their explosive rate of growth. Recently, an algorithm that can be
      implemented using adiabatic quantum evolution has been proposed that calculates
      the two-color Ramsey numbers R(m,n). Here we present results of an experimental
      implementation of this algorithm and show that it correctly determines the Ramsey
      numbers R(3,3) and R(m,2) for 4<=m<=8. The R(8,2) computation used 84 qubits of
      which 28 were computational qubits. This computation is the largest experimental
      implementation of a scientifically meaningful adiabatic evolution algorithm that
      has been done to date. 

PMID- 24116762
TI  - Multiple dynamic transitions in nonequilibrium work fluctuations.
AB  - The time-dependent work probability distribution function P(W) is investigated
      analytically for a diffusing particle trapped by an anisotropic harmonic
      potential and driven by a nonconservative drift force in two dimensions. We find
      that the exponential tail shape of P(W) characterizing rare-event probabilities
      undergoes a sequence of dynamic transitions in time. These remarkable locking
      unlocking type transitions result from an intricate interplay between a
      rotational mode induced by the nonconservative force and an anisotropic decaying
      mode due to the conservative attractive force. We expect that most of the high
      dimensional dynamical systems should exhibit similar multiple dynamic
      transitions. 

PMID- 24116763
TI  - Prompt merger collapse and the maximum mass of neutron stars.
AB  - We perform hydrodynamical simulations of neutron-star mergers for a large sample
      of temperature-dependent nuclear equations of state and determine the threshold
      mass above which the merger remnant promptly collapses to form a black hole. We
      find that, depending on the equation of state, the threshold mass is larger than
      the maximum mass of a nonrotating star in isolation by between 30 and 70 percent.
      Our simulations also show that the ratio between the threshold mass and maximum
      mass is tightly correlated with the compactness of the nonrotating maximum-mass
      configuration. We speculate on how this relation can be used to derive
      constraints on neutron-star properties from future observations. 

PMID- 24116764
TI  - Subphotospheric neutrinos from gamma-ray bursts: the role of neutrons.
AB  - Relativistic outflows with neutrons inevitably lead to inelastic collisions, and
      resulting subphotospheric gamma rays may explain prompt emission of gamma-ray
      bursts. In this model, hadronuclear, quasithermal neutrinos in the 10-100 GeV
      range should be generated, and they may even have a high-energy tail by neutron
      proton-converter or shock acceleration mechanisms. We demonstrate the importance
      of dedicated searches with DeepCore+IceCube, though such analyses have not been
      performed. Successful detections enable us to discriminate among prompt emission
      mechanisms, probe the jet composition, and see roles of relativistic neutrons as
      well as effects of cosmic-ray acceleration. 

PMID- 24116765
TI  - Neutron-proton-converter acceleration mechanism at subphotospheres of
      relativistic outflows.
AB  - We study a type of particle acceleration that operates via neutron-proton
      conversion in inelastic nuclear collisions. This mechanism can be expected for
      relativistic shocks at subphotospheres if relativistic outflows contain neutrons.
      Using a test-particle approximation, we numerically calculate the energy spectrum
      and the efficiency of accelerated particles, and show that a good energy fraction
      of the nucleons can be accelerated. This mechanism may be especially relevant if
      the shock is radiation mediated, and it would enhance the detectability of GeV
      TeV neutrinos. 

PMID- 24116766
TI  - Next-to-leading-order QCD corrections to Higgs boson production plus three jets
      in gluon fusion.
AB  - We report on the calculation of the cross section for Higgs boson production in
      association with three jets via gluon fusion, at next-to-leading-order (NLO)
      accuracy in QCD, in the infinite top-mass approximation. After including the
      complete NLO QCD corrections, we observe a strong reduction in the scale
      dependence of the result, and an increased steepness in the transverse momentum
      distributions of both the Higgs boson and the leading jets. The results are
      obtained with the combined use of GOSAM, SHERPA, and the MADDIPOLE-MADEVENT
      framework.

PMID- 24116767
TI  - Three-loop corrections to the Higgs boson mass and implications for supersymmetry
      at the LHC.
AB  - In supersymmetric models with minimal particle content and without left-right
      squark mixing, the conventional wisdom is that the 125.6 GeV Higgs boson mass
      implies top squark masses of O(10)  TeV, far beyond the reach of colliders. This
      conclusion is subject to significant theoretical uncertainties, however, and we
      provide evidence that it may be far too pessimistic. We evaluate the Higgs boson
      mass, including the dominant three-loop terms at O(alphatalphas2), in currently
      viable models. For multi-TeV top squarks, the three-loop corrections can increase
      the Higgs boson mass by as much as 3 GeV and lower the required top-squark masses
      to 3-4 TeV, greatly improving prospects for supersymmetry discovery at the
      upcoming run of the LHC and its high-luminosity upgrade.

PMID- 24116768
TI  - Finite-temperature behavior of glueballs in lattice gauge theories.
AB  - We propose a new method to compute glueball masses in finite temperature lattice
      gauge theory which at low temperature is fully compatible with the known zero
      temperature results and as the temperature increases leads to a glueball spectrum
      which vanishes at the deconfinement transition. We show that this definition is
      consistent with the Isgur-Paton model and with the expected contribution of the
      glueball spectrum to various thermodynamic quantities at finite temperature. We
      test our proposal with a set of high precision numerical simulations in the 3D
      gauge Ising model and find a good agreement with our predictions. 

PMID- 24116769
TI  - Structure of near-threshold s-wave resonances.
AB  - We study the structure of two-body s-wave bound states as well as resonances in
      the threshold energy region. We focus on the single-channel scattering where the
      scattering length and the effective range are given by real numbers. It is shown
      that, in the energy region where the effective range expansion is valid, the
      properties of resonances are constrained only by the position of the pole. We
      find that the compositeness defined through the analytic continuation of the
      field renormalization constant is purely imaginary and normalized for resonances.
      We discuss the interpretation of this quantity by examining the structure of the
      hadron resonance Lambdac(2595) in the piSigmac scattering. We show that the
      Lambdac(2595) resonance requires an unnaturally large effective range and hence
      it is not likely a piSigmac molecule.

PMID- 24116770
TI  - Decoding the riddle of Y(4260) and Zc(3900).
AB  - The observation of Zc(3900) by the BESIII Collaboration in the invariant mass
      spectrum of J/psipi+/- in e+e-->J/psipi+pi- at the center of mass 4.260 GeV
      suggests the existence of a charged DD*+DD* molecular state with I(JP)=1(1+),
      which could be an isovector brother of the famous X(3872) and an analogue of
      Zb(10610) claimed by the Belle Collaboration. We demonstrate that this
      observation provides strong evidence that the mysterious Y(4260) is a
      DD1(2420)+DD1(2420) molecular state. Especially, we show that the decay of this
      molecule naturally populates low momentum DD* pairs and leads unavoidably to a
      cusp at the DD* threshold. We discuss the signatures that distinguish such a DD*
      cusp from the presence of a true resonance.

PMID- 24116771
TI  - Efimov physics around the neutron-rich 60Ca isotope.
AB  - We calculate the neutron-60Ca S-wave scattering phase shifts using state of the
      art coupled-cluster theory combined with modern ab initio interactions derived
      from chiral effective theory. Effects of three-nucleon forces are included
      schematically as density dependent nucleon-nucleon interactions. This information
      is combined with halo effective field theory in order to investigate the 60Ca
      neutron-neutron system. We predict correlations between different three-body
      observables and the two-neutron separation energy of 62Ca. This provides evidence
      of Efimov physics along the calcium isotope chain. Experimental key observables
      that facilitate a test of our findings are discussed.

PMID- 24116772
TI  - Large beta-delayed one and two neutron emission rates in the decay of 86Ga.
AB  - Beta decay of 86Ga was studied by means of beta-neutron-gamma spectroscopy. An
      isotopically pure ^{86}Ga beam was produced at the Holifield Radioactive Ion Beam
      Facility using a resonance ionization laser ion source and high-resolution
      electromagnetic separation. The decay of 86Ga revealed a half-life of 43(
      15)(+21) ms and large beta-delayed one-neutron and two-neutron branching ratios
      of P1n=60(10)% and P2n=20(10)%. The betagamma decay of 86Ga populated a 527 keV
      transition that is interpreted as the deexcitation of the first 2+ state in the
      N=54 isotone 86Ge and suggests a quick onset of deformation in Ge isotopes beyond
      N=50.

PMID- 24116773
TI  - alpha-Particle clustering from expanding self-conjugate nuclei within the Hartree
      Fock-Bogoliubov approach.
AB  - The nuclear equation of state (EOS) is explored with the constrained Hartree-Fock
      Bogoliubov approach for self-conjugate nuclei. It is found that beyond a certain
      low, more or less universal density, those nuclei spontaneously cluster into A/4
      alpha particles with A the nucleon number. The energy at the threshold density
      increases linearly with the number of alpha particles as does the experimental
      threshold energy. Taking off the spurious c.m. energy of each alpha particle
      almost gives agreement between theory and experiment. The implications of these
      results with respect to alpha clustering and the nuclear EOS at low density are
      discussed. 

PMID- 24116774
TI  - Measurement of the neutron electric to magnetic form factor ratio at Q2=1.58 
      GeV2 using the reaction 3He[over ->](e[over ->],e'n)pp.
AB  - A measurement of beam helicity asymmetries in the reaction 3He[over ->](e[over 
      >],e'n)pp is performed at the Mainz Microtron in quasielastic kinematics to
      determine the electric to magnetic form factor ratio of the neutron GEn/GMn at a
      four-momentum transfer Q2=1.58  GeV2. Longitudinally polarized electrons are
      scattered on a highly polarized 3He gas target. The scattered electrons are
      detected with a high-resolution magnetic spectrometer, and the ejected neutrons
      are detected with a dedicated neutron detector composed of scintillator bars. To
      reduce systematic errors, data are taken for four different target polarization
      orientations allowing the determination of GEn/GMn from a double ratio. We find
      MUnGEn/GMn=0.250+/-0.058(stat)+/-0.017(syst).

PMID- 24116775
TI  - Exact tensor hypercontraction: a universal technique for the resolution of matrix
      elements of local finite-range N-body potentials in many-body quantum problems.
AB  - Configuration-space matrix elements of N-body potentials arise naturally and
      ubiquitously in the Ritz-Galerkin solution of many-body quantum problems. For the
      common specialization of local, finite-range potentials, we develop the exact
      tensor hypercontraction method, which provides a quantized renormalization of the
      coordinate-space form of the N-body potential, allowing for a highly separable
      tensor factorization of the configuration-space matrix elements. This
      representation allows for substantial computational savings in chemical, atomic,
      and nuclear physics simulations, particularly with respect to difficult
      "exchangelike" contractions. 

PMID- 24116776
TI  - Alignment-dependent fluorescence emission induced by tunnel ionization of carbon
      dioxide from lower-lying orbitals.
AB  - The study of the ionization process of molecules in an intense infrared laser
      field is of paramount interest in strong-field physics and constitutes the
      foundation of imaging of molecular valence orbitals and attosecond science. We
      show measurement of alignment-dependent ionization probabilities of the lower
      lying orbitals of the molecules by experimentally detecting the alignment
      dependence of fluorescence emission from tunnel ionized carbon dioxide molecules.
      The experimental measurements are compared with the theoretical calculations of
      the strong field approximation and molecular Ammosov-Delone-Krainov models. Our
      results demonstrate the feasibility of an all-optical approach for probing the
      ionization dynamics of lower-lying orbitals of molecules, which is until now
      still difficult to achieve by other techniques. Moreover, the deviation between
      the experimental and theoretical results indicates the incompleteness of current
      theoretical models for describing strong field ionization of molecules. 

PMID- 24116777
TI  - High-resolution probe of coherence in low-energy charge exchange collisions with
      oriented targets.
AB  - The trapping lasers of a magneto-optical trap have been used to bring Rb atoms
      into well defined oriented states. Coupled to recoil-ion-momentum spectroscopy,
      this provided a unique MOTRIMS setup which was able to probe scattering dynamics,
      including the coherence features, with unprecedented resolution. The technique
      was applied to the low-energy charge exchange reactions Na+ + Rb(5p+/-1)
      >Na(3p,4s)+Rb+. The measurements revealed detailed features of the collisional
      interaction which were employed to improve the theoretical description. As such,
      it was possible to ascertain the validity of the intuitive models used to predict
      the most likely capture transitions.

PMID- 24116778
TI  - Stern-Gerlach experiments on Mn@Sn12: identification of a paramagnetic superatom
      and vibrationally induced spin orientation.
AB  - Beam deflection experiments in inhomogeneous magnetic fields reveal a new
      limiting case of the magnetization distribution of isolated clusters.
      Endohedrally doped clusters are produced in a temperature controlled,
      cryogenically cooled laser ablation source. Temperature dependent experiments
      indicate a crucial contribution of molecular vibrations to the spin dynamics of
      Mn@Sn12. In its vibrational ground state the cluster behaves magnetically like a
      paramagnetic atom, with quantized spin states. However, excited molecular
      vibrations induce spin orientation in the magnetic field.

PMID- 24116779
TI  - Optomechanically induced transparency in the nonlinear quantum regime.
AB  - Optomechanical systems have been shown both theoretically and experimentally to
      exhibit an analogon to atomic electromagnetically induced transparency, with
      sharp transmission features that are controlled by a second laser beam. Here we
      investigate these effects in the regime where the fundamental nonlinear nature of
      the optomechanical interaction becomes important. We demonstrate that pulsed
      transistorlike switching of transmission still works even in this regime. We also
      show that optomechanically induced transparency at the second mechanical sideband
      could be a sensitive tool to see first indications of the nonlinear quantum
      nature of the optomechanical interaction even for single-photon coupling
      strengths significantly smaller than the cavity linewidth. 

PMID- 24116780
TI  - Experimental verification of isotropic radiation from a coherent dipole source
      via electric-field-driven LC resonator metamaterials.
AB  - It has long been conjectured that isotropic radiation by a simple coherent source
      is impossible due to changes in polarization. Though hypothetical, the isotropic
      source is usually taken as the reference for determining a radiator's gain and
      directivity. Here, we demonstrate both theoretically and experimentally that an
      isotropic radiator can be made of a simple and finite source surrounded by
      electric-field-driven LC resonator metamaterials designed by space manipulation.
      As a proof-of-concept demonstration, we show the first isotropic source with
      omnidirectional radiation from a dipole source (applicable to all distributed
      sources), which can open up several possibilities in axion electrodynamics,
      optical illusion, novel transformation-optic devices, wireless communication, and
      antenna engineering. Owing to the electric- field-driven LC resonator realization
      scheme, this principle can be readily applied to higher frequency regimes where
      magnetism is usually not present. 

PMID- 24116781
TI  - Coherent extreme ultraviolet light amplification by strong-field-enhanced forward
      scattering.
AB  - We theoretically study the response of He atoms exposed simultaneously to an
      intense IR pulse and a weak extreme ultraviolet (XUV) pulse with photon energies
      far from the principal atomic He resonances. We find that XUV forward scattering
      from the nonstationary electronic wave packet promoted by the intense IR driving
      field is strongly enhanced as compared with the normal weak scattering from bound
      or free electrons. Based on this effect, we predict that large amplification of
      XUV radiation can be achieved in the cutoff spectral region of high-harmonic
      generation in He gas. 

PMID- 24116782
TI  - Spiral wave chimeras in complex oscillatory and chaotic systems.
AB  - We demonstrate for the first time that spiral wave chimeras-spiral waves with
      spatially extended unsynchronzied cores-can exist in complex oscillatory and even
      locally chaotic homogeneous systems under nonlocal coupling. Using ideas from
      phase synchronization, we show in particular that the unsynchronized cores
      exhibit a distribution of different frequencies, thus generalizing the main
      concept of chimera states beyond simple oscillatory systems. In contrast to
      simple oscillatory systems, we find that spiral wave chimeras in complex
      oscillatory and locally chaotic systems are characterized by the presence of
      synchronization defect lines (SDLs), along which the dynamics follows a periodic
      behavior different from that of the bulk. Whereas this is similar to the case of
      local coupling, the type of the prevailing SDLs is very different. 

PMID- 24116783
TI  - Multicolor operation and spectral control in a gain-modulated x-ray free-electron
      laser.
AB  - We show that the spectral properties of a self-amplified spontaneous emission x
      ray free-electron laser can be controlled by modulating the gain in magnetic
      undulators, thus producing one or several spectral lines within a single few
      femtosecond pulse. By varying the magnetic field along the undulator and the
      electron beam transport line, the system we demonstrate can tailor the x-ray
      spectrum to optimally meet numerous experimental requirements for multicolor
      operation. 

PMID- 24116784
TI  - Subpicosecond bunch train production for a tunable mJ level THz source.
AB  - A strong energy modulation in an electron bunch passing through a dielectric
      lined waveguide was recently demonstrated in Antipov et al., Phys. Rev. Lett.
      108, 144801 (2012). In this Letter, we demonstrate a successful conversion of
      this energy modulation into a beam density modulation, and the formation of a
      series of microbunches with a subpicosecond periodicity by means of magnetic
      optics (chicane). A strong coherent transition radiation signal produced by the
      microbunches is obtained and the tunability of its carrier frequency in the 0.68
      0.9 THz range by regulating the energy chirp in the incoming electron bunch is
      demonstrated using infrared interferometry. A tabletop, compact, tunable, and
      narrowband source of intense THz radiation based on this technology is proposed. 

PMID- 24116785
TI  - Laser-based acceleration of nonrelativistic electrons at a dielectric structure.
AB  - A proof-of-principle experiment demonstrating dielectric laser acceleration of
      nonrelativistic electrons in the vicinity of a fused-silica grating is reported.
      The grating structure is utilized to generate an electromagnetic surface wave
      that travels synchronously with and efficiently imparts momentum on 28 keV
      electrons. We observe a maximum acceleration gradient of 25  MeV/m. We
      investigate in detail the parameter dependencies and find excellent agreement
      with numerical simulations. With the availability of compact and efficient fiber
      laser technology, these findings may pave the way towards an all-optical compact
      particle accelerator. This work also represents the demonstration of the inverse
      Smith-Purcell effect in the optical regime. 

PMID- 24116786
TI  - New electric field in asymmetric magnetic reconnection.
AB  - We present a theory and numerical evidence for the existence of a previously
      unexplored in-plane electric field in collisionless asymmetric magnetic
      reconnection. This electric field, dubbed the "Larmor electric field," is
      associated with finite Larmor radius effects and is distinct from the known Hall
      electric field. Potentially, it could be an important indicator for the upcoming
      Magnetospheric Multiscale mission to locate reconnection sites as we expect it to
      appear on the magnetospheric side, pointing earthward, at the dayside
      magnetopause reconnection site. 

PMID- 24116787
TI  - Angular-momentum evolution in laser-plasma accelerators.
AB  - The transverse properties of an electron beam are characterized by two
      quantities, the emittance which indicates the electron beam extent in the phase
      space and the angular momentum which allows for nonplanar electron trajectories.
      Whereas the emittance of electron beams produced in a laser-plasma accelerator
      has been measured in several experiments, their angular momentum has been
      scarcely studied. It was demonstrated that electrons in a laser-plasma
      accelerator carry some angular momentum, but its origin was not established. Here
      we identify one source of angular-momentum growth and we present experimental
      results showing that the angular-momentum content evolves during the
      acceleration. 

PMID- 24116788
TI  - SU(3) orbital Kondo effect with ultracold atoms.
AB  - We propose a simple but novel scheme to realize the Kondo effect with ultracold
      atoms. Our system consists of a Fermi sea of spinless fermions interacting with
      an impurity atom of different species which is confined by an isotropic
      potential. The interspecies attraction can be tuned with an s-wave Feshbach
      resonance so that the impurity atom and a spinless fermion form a bound dimer
      that occupies a threefold-degenerate p orbital of the confinement potential. Many
      body scatterings of this dimer and surrounding spinless fermions occur with
      exchanging their angular momenta and thus exhibit the SU(3) orbital Kondo effect.
      The associated Kondo temperature has a universal leading exponent given by
      TK?exp[-pi/(3apkF3)] that depends only on an effective p-wave scattering volume
      ap and a Fermi wave vector kF. We also elucidate a Kondo singlet formation at
      zero temperature and an anisotropic interdimer interaction mediated by
      surrounding spinless fermions. The Kondo effect thus realized in ultracold atom
      experiments may be observed as an increasing atom loss by lowering the
      temperature or with radio-frequency spectroscopy. Our scheme and its extension to
      a dense Kondo lattice will be useful to develop new insights into yet unresolved
      aspects of Kondo physics.

PMID- 24116789
TI  - Extracting the Chern number from the dynamics of a Fermi gas: implementing a
      quantum Hall bar for cold atoms.
AB  - We propose a scheme to measure the quantized Hall conductivity of an ultracold
      Fermi gas initially prepared in a topological Chern insulating phase and driven
      by a constant force. We show that the time evolution of the center of mass, after
      releasing the cloud, provides a direct and clear signature of the topologically
      invariant Chern number. We discuss the validity of this scheme, highlighting the
      importance of driving the system with a sufficiently strong force to displace the
      cloud over measurable distances while avoiding band-mixing effects. The unusual
      shapes of the driven atomic cloud are qualitatively discussed in terms of a
      semiclassical approach. 

PMID- 24116790
TI  - Stability and metastability of clusters in a reactive atmosphere: theoretical
      evidence for unexpected stoichiometries of MgMOx.
AB  - By applying a genetic algorithm and ab initio atomistic thermodynamics, we
      identify the stable and metastable compositions and structures of MgMOx clusters
      at realistic temperatures and oxygen pressures. We find that small clusters (M?5)
      are in thermodynamic equilibrium when x>M. The nonstoichiometric clusters exhibit
      peculiar magnetic behavior, suggesting the possibility of tuning magnetic
      properties by changing environmental pressure and temperature conditions.
      Furthermore, we show that density-functional theory with a hybrid exchange
      correlation functional is needed for predicting accurate phase diagrams of metal
      oxide clusters. Neither a (sophisticated) force field nor density-functional
      theory with (semi)local exchange-correlation functionals is sufficient for even a
      qualitative prediction.

PMID- 24116791
TI  - Universality classes in constrained crack growth.
AB  - Based on an extension of the fiber bundle model we investigate numerically the
      motion of a crack front through a weak plane separating a soft and an infinitely
      stiff block. We find that there are two regimes. At large scales the motion is
      consistent with the pinned elastic line model and we find a roughness exponent
      equal to 0.39+/-0.04 characterizing it. At smaller scales, coalescence of holes
      dominates the motion, giving a roughness exponent consistent with 2/3, the
      gradient percolation value. The length of the crack front is fractal in this
      regime. Its fractal dimension is 1.77+/-0.02, consistent with the hull of
      percolation clusters, 7/4. This suggests that the crack front is described by two
      universality classes: on large scales, the pinned elastic line one and on small
      scales, the percolation universality class. 

PMID- 24116792
TI  - Spontaneous growth of gallium-filled microcapillaries on ion-bombarded GaN.
AB  - Bottom-up growth of microscopic pillars is observed at room temperature on GaN
      irradiated with a Ga+ beam in a gaseous XeF2 environment. Ion bombardment
      produces Ga droplets which evolve into pillars, each comprised of a spherical Ga
      cap atop a Ga-filled, gallium fluoride tapered tube (sheath). The structures form
      through an interdependent, self-ordering cycle of liquid cap growth and solid
      sheath formation. The sheath and core growth mechanisms are not catalytic, but
      instead consistent with a model of ion-induced Ga and F generation, Ga transport
      through surface diffusion, and heterogeneous sputtering caused by self-masking of
      the tapered pillars.

PMID- 24116793
TI  - Densification and strain hardening of a metallic glass under tension at room
      temperature.
AB  - The deformation of metallic glasses involves two competing processes: a
      disordering process involving dilatation, free volume accumulation, and
      softening, and a relaxation process involving diffusional ordering and
      densification. For metallic glasses at room temperature and under uniaxial
      loading, disordering usually dominates, and the glass can fail catastrophically
      as the softening process runs away in a localized mode. Here we demonstrate
      conditions where the opposite, unexpected, situation occurs: the densifying
      process dominates, resulting in stable plastic deformation and work hardening at
      room temperature. We report densification and hardening during deformation in a
      Zr-based glass under multiaxial loading, in a notched tensile geometry. The
      effect is driven by stress-enhanced diffusional relaxation, and is attended by a
      reduction in exothermic heat and hardening signatures similar to those observed
      in the classical thermal relaxation of glasses. The result is significant,
      stable, plastic, extensional flow in metallic glasses, which suggest a
      possibility of designing tough glasses based on their flow properties. 

PMID- 24116794
TI  - Drastic changes in interfacial hydrodynamics due to wall slippage: slip
      intensified film thinning, drop spreading, and capillary instability.
AB  - We report that wall slippage can drastically change both steady and dynamic flow
      characteristics for a wide class of free-surface thin film flows. This is
      demonstrated by (i) the breakdown of the 2/3 law and its replacement by a new
      quadratic law for the deposited film thickness in the Landau-Levich-Bretherton
      coating, (ii) the departure from de Gennes-Tanner's cubic law for dynamic contact
      angles in drop spreading, consequently resulting in much faster spreading than
      the classical Tanner law, and (iii) the exaggerated capillary instability of an
      annular film where a fractional amount of wall slip can lead to much more rapid
      draining and hence make the film more vulnerable to rupture. In (ii), the
      molecular precursor film is shown to have a length varying like the -1/2 power of
      the spreading speed, producing an anomalous 1/3 diffusion law governing its
      spreading dynamics. A variety of existing experimental findings can be well
      captured by the new scaling laws we derive. All these features are accompanied
      with no-slip-to-slip transitions, offering alternative means for probing slip
      boundaries. 

PMID- 24116795
TI  - Conducting boron sheets formed by the reconstruction of the alpha-boron (111)
      surface.
AB  - Systematic ab initio structure prediction was applied for the first time to
      predict low energy surface reconstructions by employing the minima hopping method
      on the alpha-boron (111) surface. Novel reconstruction geometries were identified
      and carefully characterized in terms of structural and electronic properties. Our
      calculations predict the formation of a planar, monolayer sheet at the surface,
      which is responsible for conductive surface states. Furthermore, the isolated
      boron sheet is shown to be the ground state 2D structure in vacuum at a hole
      density of eta=1/5 and is therefore a potential candidate as a precursor for
      boron nanostructures. 

PMID- 24116796
TI  - Majorana fermions in vortex lattices.
AB  - We consider Majorana fermions tunneling among an array of vortices in a 2D chiral
      p-wave superconductor or equivalent material. The amplitude for Majorana fermions
      to tunnel between a pair of vortices is found to necessarily depend on the
      background superconducting phase profile; it is found to be proportional to the
      sine of half the difference between the phases at the two vortices. Using this
      result we study tight-binding models of Majorana fermions in vortices arranged in
      triangular or square lattices. In both cases we find that the aforementioned
      phase-tunneling relationship leads to the creation of superlattices where the
      Majorana fermions form macroscopically degenerate localizable flat bands at zero
      energy, in addition to other dispersive bands. This finding suggests that
      tunneling processes in these vortex arrays do not change the energies of a finite
      fraction of Majorana fermions, contrary to previous expectation. The presence of
      flat Majorana bands, and hence less-than-expected decoherence in these vortex
      arrays, bodes well for the prospects of topological quantum computation with
      large numbers of Majorana states. 

PMID- 24116797
TI  - Transport signatures of Floquet Majorana fermions in driven topological
      superconductors.
AB  - Floquet Majorana fermions are steady states of equal superposition of electrons
      and holes in a periodically driven superconductor. We study the experimental
      signatures of Floquet Majorana fermions in transport measurements and show, both
      analytically and numerically, that their presence is signaled by a quantized
      conductance sum rule over discrete values of lead bias differing by multiple
      absorption or emission energies at drive frequency. We also study the effects of
      static disorder and find that the quantized sum rule is robust against weak
      disorder. Thus, we offer a unique way to identify the topological signatures of
      Floquet Majorana fermions. 

PMID- 24116798
TI  - Observation of squeezing in the electron quantum shot noise of a tunnel junction.
AB  - We report the measurement of the fluctuations of the two quadratures of the
      electromagnetic field generated by a quantum conductor, a dc- and ac-biased
      tunnel junction placed at very low temperature. We observe that the variance of
      the fluctuations on one quadrature can go below that of vacuum, i.e., that the
      radiated field is squeezed. This demonstrates the quantum nature of the radiated
      electromagnetic field. 

PMID- 24116799
TI  - Collective spin Hall effect for electron-hole gratings.
AB  - We show that an electric field parallel to the wave fronts of an electron-hole
      grating in a GaAs quantum well generates, via the electronic spin Hall effect, a
      spin grating of the same wave vector and with an amplitude that can exceed 1% of
      the amplitude of the initial density grating. We refer to this phenomenon as the
      "collective spin Hall effect." A detailed study of the coupled spin-charge
      dynamics for quantum wells grown in different directions reveals rich features in
      the time evolution of the induced spin density, including the possibility of
      generating a helical spin grating. 

PMID- 24116800
TI  - Quantum anomalous Hall effect with higher plateaus.
AB  - The quantum anomalous Hall (QAH) effect in magnetic topological insulators is
      driven by the combination of spontaneous magnetic moments and spin-orbit
      coupling. Its recent experimental discovery raises the question if higher
      plateaus can also be realized. Here, we present a general theory for a QAH effect
      with higher Chern numbers and show by first-principles calculations that a thin
      film magnetic topological insulator of Cr-doped Bi2(Se,Te)3 is a candidate for
      the C=2 QAH insulator. Remarkably, whereas a higher magnetic field leads to lower
      Hall conductance plateaus in the integer quantum Hall effect, a higher magnetic
      moment leads to higher Hall conductance plateaus in the QAH effect.

PMID- 24116801
TI  - Direct optical coupling to an unoccupied dirac surface state in the topological
      insulator Bi2Se3.
AB  - We characterize the occupied and unoccupied electronic structure of the
      topological insulator Bi2Se3 by one-photon and two-photon angle-resolved
      photoemission spectroscopy and slab band structure calculations. We reveal a
      second, unoccupied Dirac surface state with similar electronic structure and
      physical origin to the well-known topological surface state. This state is
      energetically located 1.5 eV above the conduction band, which permits it to be
      directly excited by the output of a Ti:sapphire laser. This discovery
      demonstrates the feasibility of direct ultrafast optical coupling to a
      topologically protected, spin-textured surface state.

PMID- 24116802
TI  - Interplay of the Kondo effect and strong spin-orbit coupling in multihole
      ultraclean carbon nanotubes.
AB  - We report on cotunneling spectroscopy magnetoconductance measurements of
      multihole ultraclean carbon nanotube quantum dots in the SU(4) Kondo regime with
      strong spin-orbit coupling. Successive shells show a gradual weakening of the
      Kondo effect with respect to the spin-orbital splittings, leading to an evolution
      from SU(4) to SU(2) symmetry with a suppressed conductance at half-shell filling.
      The extracted energy level spectrum, overall consistent with negligible disorder
      in the nanotube, shows in the half filled case large renormalizations due to
      Coulombian effects. 

PMID- 24116804
TI  - Thermopower in the quantum Hall regime.
AB  - We consider the effect of disorder on the themopower in quantum Hall systems. For
      a sample in the Corbino geometry, where dissipative currents are not carried by
      edge states, we find that thermopower behaves at high temperatures like a system
      with a gap and has a maximum which increases as the temperature is reduced. At
      lower temperatures this maximum reduces as a function of temperature as a result
      of tunneling across saddle points in the background potential. Our model assumes
      that the mean saddle point height varies linearly with the deviation in filling
      factor from the quantized value. We test this hypothesis against observations for
      the dissipative electrical conductance as a function of temperature and field and
      find good agreement with experiment around the minimum. 

PMID- 24116803
TI  - Large-gap quantum spin Hall insulators in tin films.
AB  - The search for large-gap quantum spin Hall (QSH) insulators and effective
      approaches to tune QSH states is important for both fundamental and practical
      interests. Based on first-principles calculations we find two-dimensional tin
      films are QSH insulators with sizable bulk gaps of 0.3 eV, sufficiently large for
      practical applications at room temperature. These QSH states can be effectively
      tuned by chemical functionalization and by external strain. The mechanism for the
      QSH effect in this system is band inversion at the Gamma point, similar to the
      case of a HgTe quantum well. With surface doping of magnetic elements, the
      quantum anomalous Hall effect could also be realized. 

PMID- 24116805
TI  - Entanglement detection from conductance measurements in carbon nanotube cooper
      pair splitters.
AB  - Spin-orbit interaction provides a spin filtering effect in carbon nanotube based
      Cooper pair splitters that allows us to determine spin correlators directly from
      current measurements. The spin filtering axes are tunable by a global external
      magnetic field. By a bending of the nanotube, the filtering axes on both sides of
      the Cooper pair splitter become sufficiently different that a test of
      entanglement of the injected Cooper pairs through a Bell-like inequality can be
      implemented. This implementation does not require noise measurements, supports
      imperfect splitting efficiency and disorder, and does not demand a full knowledge
      of the spin-orbit strength. Using a microscopic calculation we demonstrate that
      entanglement detection by violation of the Bell-like inequality is within the
      reach of current experimental setups. 

PMID- 24116806
TI  - Shot-noise signatures of charge fractionalization in the nu=2 quantum Hall edge.
AB  - We investigate the effect of interactions on shot noise in nu=2 quantum Hall
      edges, where a repulsive coupling between copropagating edge modes is expected to
      give rise to charge fractionalization. Using the method of nonequilibrium
      bosonization, we find that even asymptotically the edge distribution function
      depends in a sensitive way on the interaction strength between the edge modes. We
      compute shot noise and the Fano factor from the asymptotic distribution function,
      and from comparison with a reference model of fractionalized excitations, we find
      that the Fano factor can be close to the value of the fractionalized charge. 

PMID- 24116807
TI  - Quantized conductance and switching in percolating nanoparticle films.
AB  - We demonstrate switching behavior and quantized conductance at room temperature
      in percolating films of nanoparticles. Our experiments and complementary
      simulations show that switching and quantization result from the formation of
      atomic-scale wires in the gaps between particles. These effects occur only when
      tunnel gaps are present in the film, close to the percolation threshold. 

PMID- 24116808
TI  - Scaling between magnetic and lattice fluctuations in iron pnictide
      superconductors.
AB  - The phase diagram of the iron arsenides is dominated by a magnetic and a
      structural phase transition, which need to be suppressed in order for
      superconductivity to appear. The proximity between the two transition temperature
      lines indicates correlation between these two phases, whose nature remains
      unsettled. Here, we find a scaling relation between nuclear magnetic resonance
      and shear modulus data in the tetragonal phase of electron-doped Ba(Fe1-xCox)2As2
      compounds. Because the former probes the strength of magnetic fluctuations while
      the latter is sensitive to orthorhombic fluctuations, our results provide strong
      evidence for a magnetically driven structural transition.

PMID- 24116809
TI  - Charge qubit coupled to an intense microwave electromagnetic field in a
      superconducting Nb device: evidence for photon-assisted quasiparticle tunneling.
AB  - We study a superconducting charge qubit coupled to an intensive electromagnetic
      field and probe changes in the resonance frequency of the formed dressed states.
      At large driving strengths, exceeding the qubit energy-level splitting, this
      reveals the well known Landau-Zener-Stuckelberg interference structure of a
      longitudinally driven two-level system. For even stronger drives, we observe a
      significant change in the Landau-Zener-Stuckelberg pattern and contrast. We
      attribute this to photon-assisted quasiparticle tunneling in the qubit. This
      results in the recovery of the qubit parity, eliminating effects of quasiparticle
      poisoning, and leads to an enhanced interferometric response. The interference
      pattern becomes robust to quasiparticle poisoning and has a good potential for
      accurate charge sensing. 

PMID- 24116810
TI  - Off-diagonal Bethe ansatz and exact solution of a topological spin ring.
AB  - A general method is proposed for constructing the Bethe ansatz equations of
      integrable models without U(1) symmetry. As an example, the exact spectrum of the
      XXZ spin ring with a Mobius-like topological boundary condition is derived by
      constructing a modified T-Q relation based on the functional connection between
      the eigenvalues of the transfer matrix and the quantum determinant of the
      monodromy matrix. With the exact solution, the elementary excitations of the
      topological XX spin ring are discussed in detail. It is found that the excitation
      spectrum indeed shows a nontrivial topological nature. 

PMID- 24116811
TI  - Fate of CPN-1 fixed points with q monopoles.
AB  - We present an extensive quantum Monte Carlo study of the Neel to valence-bond
      solid (VBS) phase transition on rectangular- and honeycomb-lattice SU(N)
      antiferromagnets in sign-problem-free models. We find that in contrast to the
      honeycomb lattice and previously studied square-lattice systems, on the
      rectangular lattice for small N, a first-order Neel-VBS transition is realized.
      On increasing N>=4, we observe that the transition becomes continuous and with
      the same universal exponents as found on the honeycomb and square lattices
      (studied here for N=5, 7, 10), providing strong support for a deconfined quantum
      critical point. Combining our new results with previous numerical and analytical
      studies, we present a general phase diagram of the stability of CPN-1 fixed
      points with q monopoles.

PMID- 24116812
TI  - Evidence for long-range spin order instead of a Peierls transition in si(553)-Au
      chains.
AB  - Stabilization of the Si(553) surface by Au adsorption results in two different
      atomically defined chain types, one of Au atoms and one of Si. At low temperature
      these chains develop two- and threefold periodicity, respectively, previously
      attributed to Peierls instabilities. Here we report evidence from scanning
      tunneling microscopy that rules out this interpretation. The *3 superstructure of
      the Si chains vanishes for low tunneling bias, i.e., close the Fermi level. In
      addition, the Au chains remain metallic despite their period doubling. Both
      observations are inconsistent with a Peierls mechanism. On the contrary, our
      results are in excellent, detailed agreement with the Si(553)-Au ground state
      predicted by density-functional theory, where the *2 periodicity of the Au chain
      is an inherent structural feature and every third Si atom is spin polarized. 

PMID- 24116813
TI  - Magnetization of SrCu2(BO3)2 in ultrahigh magnetic fields up to 118 T.
AB  - The magnetization process of the orthogonal-dimer antiferromagnet SrCu2(BO3)2 is
      investigated in high magnetic fields of up to 118 T. A 1/2 plateau is clearly
      observed in the field range 84 to 108 T in addition to 1/8, 1/4, and 1/3 plateaus
      at lower fields. Using a combination of state-of-the-art numerical simulations,
      the main features of the high-field magnetization, a 1/2 plateau of width 24 T, a
      1/3 plateau of width 34 T, and no 2/5 plateau, are shown to agree quantitatively
      with the Shastry-Sutherland model if the ratio of inter- to intradimer exchange
      interactions J'/J=0.63. It is further predicted that the intermediate phase
      between the 1/3 and 1/2 plateaus is not uniform but consists of a 1/3 supersolid
      followed by a 2/5 supersolid and possibly a domain-wall phase, with a reentrance
      into the 1/3 supersolid above the 1/2 plateau.

PMID- 24116814
TI  - Multispinon continua at zero and finite temperature in a near-ideal Heisenberg
      chain.
AB  - The space-and time-dependent response of many-body quantum systems is the most
      informative aspect of their emergent behavior. The dynamical structure factor,
      experimentally measurable using neutron scattering, can map this response in wave
      vector and energy with great detail, allowing theories to be quantitatively
      tested to high accuracy. Here, we present a comparison between neutron scattering
      measurements on the one-dimensional spin-1/2 Heisenberg antiferromagnet KCuF3,
      and recent state-of-the-art theoretical methods based on integrability and
      density matrix renormalization group simulations. The unprecedented quantitative
      agreement shows that precise descriptions of strongly correlated states at all
      distance, time, and temperature scales are now possible, and highlights the need
      to apply these novel techniques to other problems in low-dimensional magnetism.

PMID- 24116815
TI  - Photoluminescence of single-walled carbon nanotubes: the role of Stokes shift and
      impurity levels.
AB  - Recent experiments have indicated that dopants and defects can trigger new
      redshifted photoluminescence (PL) peaks below the E11 peak in single-walled
      carbon nanotubes (SWCNTs). To understand the origin of the new PL peaks, we study
      theoretically the excited-state properties of SWCNTs with some typical dopants
      and defects by ab initio many-body perturbation theory. Our calculations
      demonstrate that the Stokes shift in doped centers can be as large as 170 meV,
      which is much larger than that of intact SWCNTs and must be taken into account.
      We find dipole-allowed transitions from localized midgap and shallow impurity
      levels, which can give rise to pronounced PL peaks. Dark excitons, on the other
      hand, seem to have oscillator strengths that are too small to account for the new
      PL peaks.

PMID- 24116816
TI  - Chirality dependence of the absorption cross section of carbon nanotubes.
AB  - The variation of the optical absorption of carbon nanotubes with their geometry
      has been a long-standing question at the heart of both metrological and
      applicative issues, in particular because optical spectroscopy is one of the
      primary tools for the assessment of the chiral species abundance of samples.
      Here, we tackle the chirality dependence of the optical absorption with an
      original method involving ultraefficient energy transfer in porphyrin-nanotube
      compounds that allows uniform photoexcitation of all chiral species. We measure
      the absolute absorption cross section of a wide range of semiconducting nanotubes
      at their S22 transition and show that it varies by up to a factor of 2.2 with the
      chiral angle, with type I nanotubes showing a larger absorption. In contrast, the
      luminescence quantum yield remains almost constant.

PMID- 24116817
TI  - Surface structure of alanine on Cu(110) studied by fast atom diffraction.
AB  - We demonstrate that quantum scattering of fast atoms and molecules under grazing
      angles of incidence can be exploited to study the structure of organic molecules
      on metal surfaces. Making use of keV H and He atoms as well as H2 molecules, the
      surface structures of the chiral amino acid alanine adsorbed on a Cu(110) surface
      is studied. We present a detailed investigation on the (3*2) phase of a monolayer
      of enantiopure and racemic alanine on Cu(110), revealing the formation of an
      elongated surface unit cell of c(n*2) symmetry with n=3.16+/-0.04 for the
      sticking out methyl groups of the alanine molecules.

PMID- 24116818
TI  - Enhanced motility of a microswimmer in rigid and elastic confinement.
AB  - We analyze the effect of confining rigid and elastic boundaries on the motility
      of a model dipolar microswimmer. Flexible boundaries are deformed by the velocity
      field of the swimmer in such a way that the motility of both extensile and
      contractile swimmers is enhanced. The magnitude of the increase in swimming
      velocity is controlled by the ratio of the swimmer-advection and elastic time
      scales, and the dipole moment of the swimmer. We explain our results by
      considering swimming between inclined rigid boundaries. 

PMID- 24116819
TI  - Networklike propagation of cell-level stress in sheared random foams.
AB  - Quasistatic simple shearing flow of random monodisperse soap froth is
      investigated by analyzing surface evolver simulations of spatially periodic
      foams. Elastic-plastic behavior is caused by irreversible topological
      rearrangements (T1s) that occur when Plateau's laws are violated; the first T1
      determines the elastic limit and frequent T1 avalanches sustain the yield-stress
      plateau at large strains. The stress and shape anisotropy of individual cells is
      quantified by Q, a scalar derived from an interface tensor that gauges the cell's
      contribution to the global stress. During each T1 avalanche, the connected set of
      cells with decreasing Q, called the stress release domain, is networklike and
      nonlocal. Geometrically, the networklike nature of the stress release domains is
      corroborated through morphological analysis using the Euler characteristic. The
      stress release domain is distinctly different from the set of cells that change
      topology during a T1 avalanche. Our results highlight the connection between the
      unique rheological behavior of foams and the complex large-scale cooperative
      rearrangements of foam cells that accompany distinctly local topological
      transitions. 

PMID- 24116820
TI  - Dominant imprint of Rossby waves in the climate network.
AB  - The connectivity pattern of networks based on ground level temperature records
      shows a dense stripe of links in the extra tropics of the southern hemisphere. We
      show that statistical categorization of these links yields a clear association
      with the pattern of an atmospheric Rossby wave, one of the major mechanisms
      associated with the weather system and with planetary scale energy transport. It
      is shown that alternating densities of negative and positive links are arranged
      in half Rossby wave distances around 3500, 7000, and 10 000 km and are aligned
      with the expected direction of energy flow, distribution of time delays, and the
      seasonality of these waves. In addition, long distance links that are associated
      with Rossby waves are the most dominant in the climate network. 

PMID- 24116821
TI  - Adaptation and optimization of biological transport networks.
AB  - It has been hypothesized that topological structures of biological transport
      networks are consequences of energy optimization. Motivated by experimental
      observation, we propose that adaptation dynamics may underlie this optimization.
      In contrast to the global nature of optimization, our adaptation dynamics
      responds only to local information and can naturally incorporate fluctuations in
      flow distributions. The adaptation dynamics minimizes the global energy
      consumption to produce optimal networks, which may possess hierarchical loop
      structures in the presence of strong fluctuations in flow distribution. We
      further show that there may exist a new phase transition as there is a critical
      open probability of sinks, above which there are only trees for network
      structures whereas below which loops begin to emerge. 

PMID- 24116822
TI  - Comment on "Zeeman-driven Lifshitz transition: a model for the experimentally
      observed Fermi-surface reconstruction in YbRh2Si2".

PMID- 24116823
TI  - Hackl and Vojta reply.

PMID- 24116824
TI  - Comment on "Unified formalism of Andreev reflection at a
      ferromagnet/superconductor interface".

PMID- 24116825
TI  - Chen and Chien reply.

PMID- 24116826
TI  - Association between the c.3073A>C genetic polymorphism of the MDR1 gene and
      susceptibility to gastric cancer in the Chinese Han population.
AB  - OBJECTIVE: Gastric cancer is one of the most common malignancies in the world.
      The multidrug resistance 1 gene (MDR1) is an important candidate gene for
      influencing the susceptibility to gastric cancer. The objective of this study was
      to find out the association of MDR1 genetic variants with gastric cancer
      susceptibility in the Chinese Han population. METHODS: In total, 375 gastric
      cancer patients and 378 cancer-free controls were included. The c.3073A>C genetic
      polymorphism of the MDR1 gene was genotyped by the polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: We found that the
      genotypes/alleles from c.3073A>C genetic polymorphisms were statistically
      associated with gastric cancer risk. The risk of gastric cancer was significantly
      higher for the CC genotype as compared to the AA wild genotype (odds ratio
      [OR]=1.85, 95% confidence interval [CI] 1.15-2.97, p=0.010). The allele C may
      contribute to the susceptibility to gastric cancer (OR=1.37, 95% CI 1.10-1.70,
      p=0.005). CONCLUSION: These preliminary results indicate that the c.3073A>C
      genetic polymorphism of the MDR1 gene is potentially related to the
      susceptibility to gastric cancer in the Chinese Han population.

PMID- 24116828
TI  - What community-level strategies are needed to secure women's property rights in
      Western Kenya? Laying the groundwork for a future structural HIV prevention
      intervention.
AB  - Despite the recognized need for structural-level HIV prevention interventions
      that focus on economic empowerment to reduce women's HIV risks, few science-based
      programs have focused on securing women's land ownership as a primary or
      secondary HIV risk reduction strategy. The current study focused on a community
      led land and property rights model that was implemented in two rural areas of
      western Kenya where HIV prevalence was high (24-30%) and property rights
      violations were common. The program was designed to reduce women's HIV risk at
      the community level by protecting and enhancing women's access to and ownership
      of land. Through in-depth interviews with 50 program leaders and implementers of
      this program we sought to identify the strategies that were used to prevent,
      mediate, and resolve property rights violations. Results included four
      strategies: (1) rights-based education of both women and men individually and at
      the community level, (2) funeral committees that intervene to prevent property
      grabbing and disinheritance, (3) paralegal training of traditional leaders and
      community members and local adjudication of cases of property rights violations,
      and (4) referring property rights violations to the formal justice system when
      these are not resolved at the community level. Study participants underscored
      that local mediation of cases resulted in a higher success rate than women
      experienced in the formal court system, underscoring the importance of community
      level solutions to property rights violations. The current study assists
      researchers in understanding the steps needed to prevent and resolve women's
      property rights violations so as to bolster the literature on potential
      structural HIV prevention interventions. Future research should rigorously test
      property rights programs as a structural HIV prevention intervention.

PMID- 24116827
TI  - Bone marrow stroma-mediated resistance to FLT3 inhibitors in FLT3-ITD AML is
      mediated by persistent activation of extracellular regulated kinase.
AB  - A consistent pattern of response has been observed when FMS-like tyrosine kinase
      3 (FLT3) tyrosine kinase inhibitors (TKIs) have been used as monotherapy to treat
      patients with relapsed or refractory FLT3- internal tandem duplication (ITD)
      acute myeloid leukaemia (AML). Circulating blasts are cleared from the peripheral
      blood, while bone marrow blasts are either unaffected or are cleared from the
      marrow at a much slower rate. We used an in vitro model of FLT3-ITD AML blasts co
      cultured with normal human bone marrow stromal cells to investigate the basis for
      this dichotomous response pattern to FLT3 inhibitors. We have found that in
      blasts on stroma, potent FLT3 inhibition predominantly results in cell cycle
      arrest rather than apoptosis. The anti-apoptotic effect is mediated through a
      combination of direct cell-cell contact and soluble factors. The addition of
      exogenous FLT3 ligand (FL) augments the protection, primarily by shifting the 50%
      inhibitory concentration for FLT3 inhibition upwards. Cytokine-activated
      extracellular regulated kinase (ERK), rather than STAT5, appears to be the most
      important downstream signalling protein mediating the protective effect, and
      inhibition of MEK significantly abrogates stromal-mediated resistance. These
      findings explain the phenomenon of peripheral blood versus bone marrow blast
      responses and suggest that the combination of potent FLT3 inhibition and MEK
      inhibition is a promising strategy for the treatment of FLT3-ITD AML. 

PMID- 24116829
TI  - Monitoring the prevalence of severe intellectual disability in children across
      Europe: feasibility of a common database.
AB  - AIM: Our aim was to study the feasibility of creating a framework for monitoring
      and undertaking collaborative research on intellectual disability at the European
      level, based on existing databases of children with such disability. METHOD: The
      characteristics of five existing European intellectual disability databases from
      four countries (Iceland, Latvia, Ireland, and two in France), were discussed on
      the basis of ideal criteria set by a working group on childhood intellectual
      disability as part of the Surveillance of Cerebral Palsy in Europe Network (SCPE
      NET). Mean prevalence values for severe intellectual disability for the birth
      years 1990 till 2002 were compared across databases. RESULTS: Methods of case
      recruitment and diagnosis differed across databases, but classification of
      intellectual disability and completeness were similar. Severe intellectual
      disability (IQ<50) prevalence estimates were significantly (p<0.001) different
      across databases (south-east France: 3.3 out of 1000; south-west France: 3.0 out
      of 1000; Latvia: 3.9 out of 1000; Ireland: 5.0 out of 1000; and Iceland 5.1 out
      of 1000). INTERPRETATION: In spite of differences in diagnosis and case inclusion
      across databases, the construction of a common database for severe intellectual
      disability was deemed feasible through harmonization of certain criteria, such as
      age, and through restriction to those with severe intellectual disability.

PMID- 24116830
TI  - Interpreting a pumping test influenced by another well in an anisotropic aquifer.
AB  - In confined aquifers the influence of neighboring active wells is often neglected
      when interpreting a pumping test. This can, however, lead to an erroneous
      interpretation of the pumping test data. This article presents simple methods to
      evaluate the transmissivity tensor and storativity of an anisotropic confined
      aquifer when there is an interfering well in the neighborhood of the tested well.
      Two methods have been developed depending on whether the tested well or the
      interfering well is the first in operation. These new methods yield better
      estimates of the hydraulic parameters than when the influence of the interfering
      well is neglected. These methods have then been used on data obtained from
      numerical models with an interfering well and the results have been compared to
      an analytical method that neglects the influence of the interfering well. The
      methods require knowledge of the pumping rate of the interfering well and the
      time elapsed since the pumping started in each well. If the interfering well
      started pumping before the tested well, the method does not require knowledge of
      the aquifer piezometric level at the beginning of the test, which is often
      unknown in this case. As for the method without interference, at least three
      monitoring wells (MWs) are needed, the position of which influences the accuracy
      of the estimated parameters. Some recommendations concerning MWs position have
      been given to get more accurate results according to the sought parameter. 

PMID- 24116831
TI  - BINO(L)-based chiral receptors as fluorescent and colorimetric chemosensors for
      amino acids.
AB  - Three representative BINOL derivatives were examined for their chiral
      recognitions with D- and L-t-Boc-amino acid anions: an open system 1, which bears
      two urea groups and two pyrene groups; a closed ring system 2, which bears two
      urea groups with a closed ring system; and a dimeric system 3, which bears two
      benzylic amine groups and two pyrene groups. Dimeric system 3 displayed a
      DeltaI(D)/DeltaI(L) of 12.95 for t-Boc-alanine.

PMID- 24116832
TI  - Risk of diabetes in subjects with sedentary profession and the synergistic effect
      of positive family history of diabetes.
AB  - BACKGROUND: Sedentarism in the workplace, which accelerates risk of diabetes, is
      least explored in the Indian population. The primary objective of this study was
      to assess whether prolonged sitting hours in work place predisposes individuals
      to risk of diabetes and also to estimate risk of diabetes in sedentary workers
      with a positive family history of diabetes (FHD). SUBJECTS AND METHODS: Data of
      age-matched 514 subjects previously undiagnosed with diabetes from two different
      occupational groups (bank employees and schoolteachers) in Chennai, India from
      opportunistic screening were taken for analysis. The important explanatory
      variables were body mass index, waist circumference, duration of physical
      activity, positive FHD, and random capillary blood glucose (RCBG). Logistic
      regression analyses were done separately to identify determinants of diabetes in
      each group. Another logistic regression was performed after combining data to
      estimate risk associated with diabetes among sedentary subjects with positive
      FHD. RESULTS: Factors associated with elevated RCBG among schoolteachers were
      systolic and diastolic blood pressure, whereas among bank employees, in addition
      to blood pressure, duration of sitting in work place and positive FHD were
      significantly associated with diabetes. Combined data analysis showed that
      subjects with duration of sitting of >=180 min/day and a positive FHD are three
      times at risk of developing diabetes. Adjusting for total physical activity
      revealed that risk was higher among male subjects. CONCLUSIONS: Increased sitting
      duration for >=180 min/day at the workplace was associated with elevated RCBG.
      There was a threefold higher risk for diabetes among these subjects with positive
      FHD. Encouraging physical activities in such groups, particularly in men, can be
      beneficial.

PMID- 24116833
TI  - [13C]glucose breath testing provides a noninvasive measure of insulin resistance:
      calibration analyses against clamp studies.
AB  - BACKGROUND: Exhaled (13)CO2 following ingestion of [(13)C]glucose with a standard
      oral glucose tolerance load correlates with blood glucose values but is
      determined by tissue glucose uptake. Therefore exhaled (13)CO2 may also be a
      surrogate measure of the whole-body glucose disposal rate (GDR) measured by the
      gold standard hyperinsulinemic euglycemic clamp. SUBJECTS AND METHODS: Subjects
      from across the glycemia range were studied on 2 consecutive days under fasting
      conditions. On Day 1, a 75-g oral glucose load spiked with [(13)C]glucose was
      administered. On Day 2, a hyperinsulinemic euglycemic clamp was performed.
      Correlations between breath parameters and clamp-derived GDR were evaluated, and
      calibration analyses were performed to evaluate the precision of breath parameter
      predictions of clamp measures. RESULTS: Correlations of breath parameters with
      GDR and GDR per kilogram of fat-free mass (GDRffm) ranged from 0.54 to 0.61 and
      0.54 to 0.66, respectively (all P<0.001). In calibration analyses the root mean
      square error for breath parameters predicting GDR and GDRffm ranged from 2.32 to
      2.46 and from 3.23 to 3.51, respectively. Cross-validation prediction error
      (CVPE) estimates were 2.35-2.51 (GDR) and 3.29-3.57 (GDRffm). Prediction
      precision of breath enrichment at 180 min predicting GDR (CVPE=2.35) was superior
      to that for inverse insulin (2.68) and the Matsuda Index (2.51) but inferior to
      that for the log of homeostasis model assessment (2.21) and Quantitative Insulin
      Sensitivity Check Index (2.29) (all P<10(-5)). Similar patterns were seen for
      predictions of GDRffm. CONCLUSIONS: (13)CO2 appearance in exhaled breath
      following a standard oral glucose load with added [(13)C]glucose provides a valid
      surrogate index of clamp-derived measures of whole-body insulin resistance, with
      good accuracy and precision. This noninvasive breath test-based approach can
      provide a useful measure of whole-body insulin resistance in physiologic and
      epidemiologic studies.

PMID- 24116834
TI  - Malignant and benign forms of atrophic papulosis (Kohlmeier-Degos disease):
      systemic involvement determines the prognosis.
AB  - BACKGROUND: Atrophic papulosis (Kohlmeier-Degos disease) is a rare disease of
      unknown aetiology. The cutaneous signs--papular skin lesions with central
      porcelain-white atrophy and surrounding telangiectatic rim--are almost
      pathognomonic. Extracutaneous, systemic involvement includes multiple limited
      infarcts of the gastrointestinal system, central nervous system and other organs.
      OBJECTIVES: To assess prospectively the demographics, epidemiological data and
      prognosis of patients with atrophic papulosis evaluated in a single centre.
      METHODS: A prospective, single-centre, cohort study at diagnosis was performed on
      a series of 39 patients with atrophic papulosis, first seen between 2000 and 2007
      and evaluated up to 2012. RESULTS: The occurrence of cutaneous lesions defined
      the onset of disease in all cases. The mean age of onset was 35.4 +/- 12.3 years
      and the male-to-female ratio was 1 : 1.4. In total, 9% of patients reported
      familial occurrence. Extracutaneous (systemic) signs were recorded in 29% of the
      patients, whereas the median time for development of systemic manifestations was
      1 year (0.03-0.97 quantiles: 0-7 years) after the occurrence of cutaneous
      lesions. The prognosis was determined mainly by the presence of systemic
      involvement. 73% of the patients with systemic manifestations (73% developed
      intestinal perforation) died, while none of the patients with only cutaneous
      disease had a lethal outcome. The cumulative 5-year survival rate in patients
      with systemic disease was 54.5%. CONCLUSIONS: Atrophic papulosis, previously
      called malignant atrophic papulosis, should be classified into a malignant,
      systemic form and a benign, cutaneous one, the latter being more common. The
      probability of having a benign form of the disease at onset is approximately 70%,
      increasing to 97% after 7 years of monosymptomatic cutaneous course.

PMID- 24116835
TI  - Glabellar red dots in frontal fibrosing alopecia: a further clinical sign of
      vellus follicle involvement.

PMID- 24116836
TI  - Chromosomal microaberrations in patients with epilepsy, intellectual disability,
      and congenital anomalies.
AB  - Epilepsy is a common finding in patients with chromosomal macro- and micro
      rearrangements but only few aberrations show a constant pattern of seizures. DNA
      array-based studies have reported causative copy number variations (CNVs) in 5
      30% of patients with epilepsy with or without co-morbidities. The interpretation
      of many of the detected CNVs remains challenging. In order to identify CNVs
      carrying epilepsy-related genes we investigated 43 children with various patterns
      of epileptic seizures, intellectual disability (ID), and minor dysmorphism, using
      the Illumina(r) Infinium Human1M-DuoV1 array. In three patients we found likely
      causative de novo CNVs, i.e. deletions in 1q41q42.12 (3.4 Mb) and 19p13.2 (834
      kb), and a mosaic two-segment duplication in 17p13.2 (218 kb) and 17p13.1 (422
      kb). In six additional patients there were aberrations (a deletion in one and
      duplications in five patients) with uncertain clinical consequences. In total,
      the finding of causative chromosomal micro-rearrangements in 3 out of 43 patients
      (7%) and potentially causative CNVs in 6 additional patients (14%) with epilepsy
      and ID but without major malformations confirms the power of DNA arrays for the
      detection of new disease-related genetic regions. 

PMID- 24116837
TI  - How European American and Taiwanese mothers talk to their children about
      learning.
AB  - Little cross-cultural research exists on parental socialization of children's
      learning beliefs. The current study compared 218 conversations between European
      American and Taiwanese mothers and children (6-10 years) about good and poor
      learning. The findings support well-documented cultural differences in learning
      beliefs. European Americans mentioned mental activities and positive affect more,
      whereas Taiwanese mentioned learning virtues and negative affect more. Mothers,
      especially European American, reciprocated their children's talk about mental
      activities, learning virtues, and negative affect. Children, especially
      Taiwanese, reciprocated their mother's talk about positive affect. Mothers
      invoked more mental activities and positive affect when discussing good learning,
      but more learning virtues and negative affect when discussing poor learning.
      These findings reveal a source of cultural differences in beliefs and potential
      enculturation.

PMID- 24116838
TI  - Effects of literacy in early visual and occipitotemporal areas of Chinese and
      French readers.
AB  - How does reading expertise change the visual system? Here, we explored whether
      the visual system could develop dedicated perceptual mechanisms in early and
      intermediate visual cortex under the pressure for fast processing that is
      particularly strong in reading. We compared fMRI activations in Chinese
      participants with limited knowledge of French and in French participants with no
      knowledge of Chinese, exploiting these doubly dissociated reading skills as a
      tool to study the neural correlates of visual expertise. All participants viewed
      the same stimuli: words in both languages and matched visual controls, presented
      at a fast rate comparable with fluent reading. In the Visual Word Form Area, all
      participants showed enhanced responses to their known scripts. However, group
      differences were found in occipital cortex. In French readers reading French,
      activations were enhanced in left-hemisphere visual area V1, with the strongest
      differences between French words and their controls found at the central and
      horizontal meridian representations. Chinese participants, who were not expert
      French readers, did not show these early visual activations. In contrast, Chinese
      readers reading Chinese showed enhanced activations in intermediate visual areas
      V3v/hV4, absent in French participants. Together with our previous findings
      [Szwed, M., Dehaene, S., Kleinschmidt, A., Eger, E., Valabregue, R., Amadon, A.,
      et al. Specialization for written words over objects in the visual cortex.
      Neuroimage, 56, 330-344, 2011], our results suggest that the effects of extensive
      practice can be found at the lowest levels of the visual system. They also reveal
      their cross-script variability: Alphabetic reading involves enhanced engagement
      of central and right meridian V1 representations that are particularly used in
      left-to-right reading, whereas Chinese characters put greater emphasis on
      intermediate visual areas. 

PMID- 24116839
TI  - CoCoTools: open-source software for building connectomes using the CoCoMac
      anatomical database.
AB  - Neuroanatomical tracer studies in the nonhuman primate macaque monkey are a
      valuable resource for cognitive neuroscience research. These data ground theories
      of cognitive function in anatomy, and with the emergence of graph theoretical
      analyses in neuroscience, there is high demand for these data to be consolidated
      into large-scale connection matrices ("macroconnectomes"). Because manual review
      of the anatomical literature is time consuming and error prone, computational
      solutions are needed to accomplish this task. Here we describe the "CoCoTools"
      open-source Python library, which automates collection and integration of macaque
      connectivity data for visualization and graph theory analysis. CoCoTools both
      interfaces with the CoCoMac database, which houses a vast amount of annotated
      tracer results from 100 years (1905-2005) of neuroanatomical research, and
      implements coordinate-free registration algorithms, which allow studies that use
      different parcellations of the brain to be translated into a single graph. We
      show that using CoCoTools to translate all of the data stored in CoCoMac produces
      graphs with properties consistent with what is known about global brain
      organization. Moreover, in addition to describing CoCoTools' processing pipeline,
      we provide worked examples, tutorials, links to on-line documentation, and
      detailed appendices to aid scientists interested in using CoCoTools to gather and
      analyze CoCoMac data. 

PMID- 24116840
TI  - Opposing dorsal/ventral stream dynamics during figure-ground segregation.
AB  - The visual system has been commonly subdivided into two segregated visual
      processing streams: The dorsal pathway processes mainly spatial information, and
      the ventral pathway specializes in object perception. Recent findings, however,
      indicate that different forms of interaction (cross-talk) exist between the
      dorsal and the ventral stream. Here, we used TMS and concurrent EEG recordings to
      explore these interactions between the dorsal and ventral stream during figure
      ground segregation. In two separate experiments, we used repetitive TMS and
      single-pulse TMS to disrupt processing in the dorsal (V5/HMT+) and the ventral
      (lateral occipital area) stream during a motion-defined figure discrimination
      task. We presented stimuli that made it possible to differentiate between
      relatively low-level (figure boundary detection) from higher-level (surface
      segregation) processing steps during figure-ground segregation. Results show that
      disruption of V5/HMT+ impaired performance related to surface segregation; this
      effect was mainly found when V5/HMT+ was perturbed in an early time window (100
      msec) after stimulus presentation. Surprisingly, disruption of the lateral
      occipital area resulted in increased performance scores and enhanced neural
      correlates of surface segregation. This facilitatory effect was also mainly found
      in an early time window (100 msec) after stimulus presentation. These results
      suggest a "push-pull" interaction in which dorsal and ventral extrastriate areas
      are being recruited or inhibited depending on stimulus category and task demands.

PMID- 24116841
TI  - Integrating the behavioral and neural dynamics of response selection in a dual
      task paradigm: a dynamic neural field model of Dux et al. (2009).
AB  - People are typically slower when executing two tasks than when only performing a
      single task. These dual-task costs are initially robust but are reduced with
      practice. Dux et al. (2009) explored the neural basis of dual-task costs and
      learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic
      response on dual-task trials compared with single-task trial early in learning.
      As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to
      single-task levels. Dux and colleagues concluded that the reduction of dual-task
      costs is accomplished through increased efficiency of information processing in
      IFJ. We present a dynamic field theory of response selection that addresses two
      questions regarding these results. First, what mechanism leads to the reduction
      of dual-task costs and associated changes in hemodynamics? We show that a simple
      Hebbian learning mechanism is able to capture the quantitative details of
      learning at both the behavioral and neural levels. Second, is efficiency isolated
      to cognitive control areas such as IFJ, or is it also evident in sensory motor
      areas? To investigate this, we restrict Hebbian learning to different parts of
      the neural model. None of the restricted learning models showed the same
      reductions in dual-task costs as the unrestricted learning model, suggesting that
      efficiency is distributed across cognitive control and sensory motor processing
      systems.

PMID- 24116842
TI  - Influencing food choices by training: evidence for modulation of frontoparietal
      control signals.
AB  - To overcome unhealthy behaviors, one must be able to make better choices.
      Changing food preferences is an important strategy in addressing the obesity
      epidemic and its accompanying public health risks. However, little is known about
      how food preferences can be effectively affected and what neural systems support
      such changes. In this study, we investigated a novel extensive training paradigm
      where participants chose from specific pairs of palatable junk food items and
      were rewarded for choosing the items with lower subjective value over higher
      value ones. In a later probe phase, when choices were made for real consumption,
      participants chose the lower-valued item more often in the trained pairs compared
      with untrained pairs. We replicated the behavioral results in an independent
      sample of participants while they were scanned with fMRI. We found that, as
      training progressed, there was decreased recruitment of regions that have been
      previously associated with cognitive control, specifically the left dorsolateral
      pFC and bilateral parietal cortices. Furthermore, we found that connectivity of
      the left dorsolateral pFC was greater with primary motor regions by the end of
      training for choices of lower-valued items that required exertion of self
      control, suggesting a formation of a stronger stimulus-response association.
      These findings demonstrate that it is possible to influence food choices through
      training and that this training is associated with a decreasing need for top-down
      frontoparietal control. The results suggest that training paradigms may be
      promising as the basis for interventions to influence real-world food
      preferences. 

PMID- 24116843
TI  - Direct control of visual perception with phase-specific modulation of posterior
      parietal cortex.
AB  - We examined the causal relationship between the phase of alpha oscillations (9-12
      Hz) and conscious visual perception using rhythmic TMS (rTMS) while
      simultaneously recording EEG activity. rTMS of posterior parietal cortex at an
      alpha frequency (10 Hz), but not occipital or sham rTMS, both entrained the phase
      of subsequent alpha oscillatory activity and produced a phase-dependent change on
      subsequent visual perception, with lower discrimination accuracy for targets
      presented at one phase of the alpha oscillatory waveform than for targets
      presented at the opposite phase. By extrinsically manipulating the phase of alpha
      before stimulus presentation, we provide direct evidence that the neural
      circuitry in the parietal cortex involved with generating alpha oscillations
      plays a causal role in determining whether or not a visual stimulus is
      successfully perceived. 

PMID- 24116844
TI  - Dynamic parieto-premotor network for mental image transformation revealed by
      simultaneous EEG and fMRI measurement.
AB  - Previous studies have suggested that the posterior parietal cortices and premotor
      areas are involved in mental image transformation. However, it remains unknown
      whether these regions really cooperate to realize mental image transformation. In
      this study, simultaneous EEG and fMRI were performed to clarify the spatio
      temporal properties of neural networks engaged in mental image transformation. We
      adopted a modified version of the mental clock task used by Sack et al. [Sack, A.
      T., Camprodon, J. A., Pascual-Leone, A., & Goebel, R. The dynamics of
      interhemispheric compensatory processes in mental imagery. Science, 308, 702-704,
      2005; Sack, A. T., Sperling, J. M., Prvulovic, D., Formisano, E., Goebel, R., Di
      Salle, F., et al. Tracking the mind's image in the brain II: Transcranial
      magnetic stimulation reveals parietal asymmetry in visuospatial imagery. Neuron,
      35, 195-204, 2002]. In the modified mental clock task, participants mentally
      rotated clock hands from the position initially presented at a learned speed for
      various durations. Subsequently, they matched the position to the visually
      presented clock hands. During mental rotation of the clock hands, we observed
      significant beta EEG suppression with respect to the amount of mental rotation at
      the right parietal electrode. The beta EEG suppression accompanied activity in
      the bilateral parietal cortices and left premotor cortex, representing a dynamic
      cortical network for mental image transformation. These results suggest that
      motor signals from the premotor area were utilized for mental image
      transformation in the parietal areas and for updating the imagined clock hands
      represented in the right posterior parietal cortex. 

PMID- 24116846
TI  - Intensity of menstrual pain and estimated angle of uterine flexion.
AB  - OBJECTIVE: To assess the impact of ultrasound-estimated uterus position on the
      intensity of pelvic pain. DESIGN: Descriptive analytical study. SETTING: Tertiary
      university gynecology unit. POPULATION: 181 consecutive patients with pelvic
      pain. METHODS: Each woman underwent physical examination, transvaginal sonography
      and filled self-administered questionnaires on pain using a 10-cm visual analog
      scale (VAS). MAIN OUTCOME MEASURES: Visual analog scale score of menstrual pain,
      intermenstrual pain and dyspareunia was related to uterine version (ante- or
      retroversion) and the angle of uterine flexion (actual angle between cervix and
      uterine body) evaluated by transvaginal sonography. RESULTS: Estimated uterine
      version was not associated with the intensity of any type of pain. The estimated
      angle of flexion was higher in retroverted than in anteverted uteri (182.3
      degrees  +/- 50.3 degrees  vs. 142.3 degrees  +/- 24.2 degrees , p < 0.0001).
      Intensity of menstrual pain was lowest with flexion between 150 degrees  and 210
      degrees  (4.9 +/- 3.1) (p = 0.002), intermediate with flexion <150 degrees  (6.3
      +/- 2.8) and highest with flexion >=210 degrees  (7.9 +/- 2.3). Severe menstrual
      pain was more prevalent with flexion >=210 degrees  (77.7%) than between 150
      degrees  and 210 degrees  (31.4%; p = 0.0008) or <150 degrees  (45.2%; p =
      0.005). The intensity of intermenstrual pain and dyspareunia were not associated
      with the angle of flexion. In multiple regression analysis, the angle of flexion
      was independently related only to the intensity of menstrual pain (r = 0.272; p =
      0.002). CONCLUSIONS: In women with pelvic pain, ultrasound-estimated uterine
      flexion represents an independent risk for intense menstrual pain.

PMID- 24116845
TI  - Identification of a novel HLA-B allele, B*27:102, in a Brazilian individual.
AB  - The HLA-B*27:102 allele may have originated by an intralocus gene conversion
      event. 

PMID- 24116847
TI  - A dual process account of coarticulation in motor skill acquisition.
AB  - Many tasks, such as typing a password, are decomposed into a sequence of subtasks
      that can be accomplished in many ways. Behavior that accomplishes subtasks in
      ways that are influenced by the overall task is often described as "skilled" and
      exhibits coarticulation. Many accounts of coarticulation use search methods that
      are informed by representations of objectives that define skilled. While they aid
      in describing the strategies the nervous system may follow, they are
      computationally complex and may be difficult to attribute to brain structures.
      Here, the authors present a biologically- inspired account whereby skilled
      behavior is developed through 2 simple processes: (a) a corrective process that
      ensures that each subtask is accomplished, but does not do so skillfully and (b)
      a reinforcement learning process that finds better movements using trial and
      error search that is not informed by representations of any objectives. We
      implement our account as a computational model controlling a simulated two-armed
      kinematic "robot" that must hit a sequence of goals with its hands. Behavior
      displays coarticulation in terms of which hand was chosen, how the corresponding
      arm was used, and how the other arm was used, suggesting that the account can
      participate in the development of skilled behavior.

PMID- 24116848
TI  - Surface structure-dependent molecular oxygen activation of BiOCl single
      crystalline nanosheets.
AB  - We demonstrate that BiOCl single-crystalline nanosheets possess surface structure
      dependent molecular oxygen activation properties under UV light. The (001)
      surface of BiOCl prefers to reduce O2 to .O2(-) through one-electron transfer,
      while the (010) surface favors the formation of O2(2-) via two-electron transfer,
      which is cogoverned by the surface atom exposure and the situ generated oxygen
      vacancy characteristics of the (001) and (010) surfaces under UV light
      irradiation. 

PMID- 24116851
TI  - Measurement of the Md3+/Md2+ reduction potential studied with flow electrolytic
      chromatography.
AB  - The reduction behavior of mendelevium (Md) was studied using a flow electrolytic
      chromatography apparatus. By application of the appropriate potentials on the
      chromatography column, the more stable Md(3+) is reduced to Md(2+). The reduction
      potential of the Md(3+) + e(-) -> Md(2+) couple was determined to be -0.16 +/-
      0.05 V versus a normal hydrogen electrode. 

PMID- 24116850
TI  - Endothelial expression of CXCR7 and the regulation of systemic CXCL12 levels.
AB  - The concentration of CXCL12/SDF-1 in the bloodstream is tightly regulated, given
      its central role in leucocyte and stem/progenitor cell egress from bone marrow
      and recruitment to sites of inflammation or injury. The mechanism responsible for
      this regulation is unknown. Here we show that both genetic deletion and
      pharmacological inhibition of CXCR7, a high-affinity CXCL12 receptor, caused
      pronounced increases in plasma CXCL12 levels. The rise in plasma CXCL12 levels
      was associated with an impairment in the ability of leucocytes to migrate to a
      local source of CXCL12. Using a set of complementary and highly sensitive
      techniques, we found that CXCR7 protein is expressed at low levels in multiple
      organs in both humans and mice. In humans, CXCR7 was detected primarily on venule
      endothelium and arteriole smooth muscle cells. CXCR7 expression on venule
      endothelium was also documented in immunodeficient mice and CXCR7(+/lacZ) mice.
      The vascular expression of CXCR7 therefore gives it immediate access to
      circulating CXCL12. These studies suggest that endothelial CXCR7 regulates
      circulating CXCL12 levels and that CXCR7 inhibitors might be used to block CXCL12
      mediated cell migration for therapeutic purposes. 

PMID- 24116849
TI  - Quality control gone wrong: mitochondria, lysosomal storage disorders and
      neurodegeneration.
AB  - The eukaryotic cell possesses specialized pathways to turn over and degrade
      redundant proteins and organelles. Each pathway is unique and responsible for
      degradation of distinctive cytosolic material. The ubiquitin-proteasome system
      and autophagy (chaperone-mediated, macro, micro and organelle specific) act
      synergistically to maintain proteostasis. Defects in this equilibrium can be
      deleterious at cellular and organism level, giving rise to various disease
      states. Dysfunction of quality control pathways are implicated in
      neurodegenerative diseases and appear particularly important in Parkinson's
      disease and the lysosomal storage disorders. Neurodegeneration resulting from
      impaired degradation of ubiquitinated proteins and alpha-synuclein is often
      accompanied by mitochondrial dysfunction. Mitochondria have evolved to control a
      diverse number of processes, including cellular energy production, calcium
      signalling and apoptosis, and like every other organelle within the cell, they
      must be 'recycled.' Failure to do so is potentially lethal as these once
      indispensible organelles become destructive, leaking reactive oxygen species and
      activating the intrinsic cell death pathway. This process is paramount in neurons
      which have an absolute dependence on mitochondrial oxidative phosphorylation as
      they cannot up-regulate glycolysis. As such, mitochondrial bioenergetic failure
      can underpin neural death and neurodegenerative disease. In this review, we
      discuss the links between cellular quality control and neurodegenerative diseases
      associated with mitochondrial dysfunction, with particular attention to the
      emerging links between Parkinson's and Gaucher diseases in which defective
      quality control is a defining factor.

PMID- 24116852
TI  - Age, stress, and isolation in older adults living with HIV.
AB  - People living with HIV (PLWH) have increasingly longer life spans. This age group
      faces different challenges than younger PLWH, which may include increased stress
      and social isolation. The purpose of this study was to determine whether the age
      and sex of PLWH are associated with measures of physiologic stress, perceived
      stress, and social isolation. In this cross-sectional study, we enrolled 102 PLWH
      equally into four groups divided by age (younger or older than 50 years) and
      gender. Participants completed well-validated survey measurements of stress and
      isolation, and their heart rate variability over 60 minutes was measured by
      Holter monitor. The mean (SD) Perceived Stress Scale score was 17.4 (6.94), mean
      Visual Analog Stress Scale score was 3.51 (2.79), and mean Hawthorne Friendship
      Scale score, a measure of social isolation, was 17.03 (4.84). Mean heart rate
      variability expressed as the SD of successive N-N intervals was 65.47 (31.16)
      msec. In multivariable regression models that controlled for selected demographic
      variables, there was no relationship between the Perceived Stress Scale and age
      (coefficient = -0.09, p =-0.23) or female gender (coefficient = -0.12, p = 0.93);
      however, there was a modest relationship between female gender and stress using
      the Visual Analog Stress Scale (coefficient = 1.24, p = 0.05). Perceived Stress
      was negatively associated with the Hawthorne Friendship score (coefficient = 
      0.34, p = 0.05). Hawthorne Friendship score was positively associated with
      younger age (coefficient = 0.11, p = 0.02). Age was the only independent
      predictor of physiologic stress as measured by heart rate variability
      (coefficient = -1.3, p < 0.01). Our findings suggest that younger PLWH may
      experience more social isolation; however, age-related changes in heart rate
      variability do not appear to be related to perceived stress or social isolation.
      Future longitudinal research is required to more thoroughly understand this
      relationship and its impact on the health of PLWH. 

PMID- 24116854
TI  - Secondary peritonitis due to Rhizobium radiobacter.
AB  - BACKGROUND: Rhizobium radiobacter rarely causes human infections, most of which
      develop in immunocompromised patients, and especially those with intravenous
      catheters. Although R. radiobacter has been reported in association with
      peritonitis, all such reported cases have been due to intra-peritoneal devices in
      patients undergoing peritoneal dialysis. Herein we report the first case of a
      perforated ulcer complicated by peritonitis caused by R. radiobacter in a healthy
      adult, which was treated successfully with surgery and antibiotics. METHODS: Case
      report and literature review. RESULTS: A 33-year-old male presented with
      epigastric abdominal pain of sudden onset. Physical examination was unremarkable
      except for the finding of diffuse abdominal tenderness with rebound tenderness.
      Exploratory laparotomy revealed a perforated duodenal ulcer with secondary
      peritonitis. The patient underwent pyloroplasty with bilateral truncal vagotomy
      and peritoneal toilet. Turbid ascites was sent for culture and yielded R.
      radiobacter and Streptococcus viridans. The patient was treated with a 10-d
      course of ceftazidime on the basis of drug susceptibility results, and recovered
      completely without complications. CONCLUSIONS: We report a case of secondary
      peritonitis caused by R. radiobacter, which expands the spectrum of infectious
      diseases caused by this organism.

PMID- 24116853
TI  - Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies:
      results of a phase III, double-blind, randomized, placebo-controlled, flexible
      dose trial.
AB  - PURPOSE: To evaluate the safety and tolerability of adjunctive brivaracetam
      (BRV), a high-affinity synaptic vesicle protein 2A (SV2A) ligand, in adults with
      uncontrolled epilepsy. Efficacy was also assessed in patients with focal seizures
      as a secondary objective, and explored by descriptive analysis in patients with
      generalized seizures. METHODS: This was a phase III, randomized, double-blind,
      placebo (PBO)-controlled flexible dose trial (N01254/NCT00504881) in adults (16
      70 years) with uncontrolled epilepsy (up to 20% could be patients with
      generalized epilepsy). After a prospective 4-week baseline, patients were
      randomized (3:1) to b.i.d. BRV or PBO, initiated at 20 mg/day and increased, as
      needed, to 150 mg/day during an 8-week dose-finding period. This was followed by
      an 8-week stable-dose maintenance period. The treatment period comprised the dose
      finding period plus the maintenance period (16 weeks). KEY FINDINGS: A total of
      480 patients were randomized (BRV 359, PBO 121); of these, 431 had focal epilepsy
      and 49 had generalized epilepsy. Ninety percent BRV- and 91.7% PBO-treated
      patients completed the study. Similar proportions of patients (BRV 66.0%, PBO
      65.3%) reported adverse events (AEs) during the treatment period. AEs led to
      treatment discontinuation in 6.1% and 5.0% of BRV- and PBO-treated patients,
      respectively. The incidence of AEs declined from the dose-finding (BRV 56.0%, PBO
      55.4%) to the maintenance (BRV 36.8%, PBO 40.9%) period. The most frequent AEs
      during the treatment period were headache (BRV 14.2% vs. PBO 19.8%), somnolence
      (BRV 11.1% vs. PBO 4.1%), and dizziness (BRV 8.6% vs. PBO 5.8%). The incidence of
      psychiatric AEs was similar for BRV and PBO (BRV 12.3%, PBO 11.6%). In patients
      with focal seizures, the baseline-adjusted percent reduction in seizure
      frequency/week in the BRV group (n = 323) over PBO (n = 108) was 7.3% (p = 0.125)
      during the treatment period. The median percent reduction in baseline-adjusted
      seizure frequency/week was 26.9% BRV versus 18.9% PBO (p = 0.070), and the >=50%
      responder rate was 30.3% BRV versus 16.7% PBO (p = 0.006). In patients with
      generalized seizures only, the number of seizure days/week decreased from 1.42 at
      baseline to 0.63 during the treatment period in BRV-treated patients (n = 36),
      and from 1.47 at baseline to 1.26 during the treatment period in PBO-treated
      patients (n = 13). The median percent reduction from baseline in generalized
      seizure days/week was 42.6% versus 20.7%, and the >=50% responder rate was 44.4%
      versus 15.4% in BRV-treated and PBO-treated patients, respectively. SIGNIFICANCE:
      Adjunctive BRV given at individualized tailored doses (20-150 mg/day) was well
      tolerated in adults with uncontrolled epilepsy, and our results provided support
      for further evaluation of efficacy in reducing focal and generalized seizures.

PMID- 24116855
TI  - Shewanella algae: a rare cause of necrotizing fasciitis.
AB  - BACKGROUND: The genus Shewanella consists of motile, gram-negative, facultative
      anaerobes found in marine environments. Shewanella putrefaciens and Shewanella
      algae are the two species with documented pathogenicity in human beings. Most
      documented cases of S. algae infection worldwide have been reported in the
      context of bacteremia, cellulitis, and acute exacerbations of chronic otitis
      media in predisposed individuals. We report a rare case of necrotizing soft
      tissue infection by S. algae in an immunocompetent individual. The infection
      followed exposure to S. algae in contaminated water in New York City, New York.
      METHODS: We reviewed the English-language literature on similar cases of soft
      tissue infection using PubMed. Search terms included "Shewanella algae" and
      "Shewanella putrefaciens" in conjunction with "necrotizing" and "infection."
      Cognizant that this search method may not have yielded early (pre-1985) reports
      about Shewanella because of changes in classification and nomenclature, we also
      searched for "Pseudomonas putrefaciens." RESULTS: After prompt surgical
      debridement and culture-directed antibiotic therapy, the patient recovered from
      his infection without the need for re-intervention. CONCLUSIONS: This case may
      reflect the geographic spread and emergence of S. algae infection in the United
      States. Clinicians should be aware of the virulence of S. algae and potential for
      the rapid clinical deterioration of persons it infects even among immunocompetent
      individuals.

PMID- 24116856
TI  - Tricuspid valve mycetoma in an infant successfully treated by excision and
      complex tricuspid valve repair followed by fluconazole therapy.
AB  - BACKGROUND: Fungal valve endocarditis in children is an uncommon and lethal
      disease. The risk increases with use of central venous catheters (CVC), total
      parenteral nutrition (TPN), and use of broad-spectrum antibiotics during the
      neonatal period. Due to high mortality, a combination of surgery and antifungal
      therapy is usually recommended for treatment. METHODS: Case report and review of
      the literature. RESULTS: We present a case of an asymptomatic infant with
      multiple Candida tricuspid valve mycetomas. Complete cure was achieved by
      combined tricuspid valve repair and fluconazole therapy. We also review 26 cases
      of tricuspid valve Candida endocarditis in children published in the literature.
      CONCLUSION: From being uniformly fatal five decades ago to a current survival
      rate of 64% to 100%, the prognosis of Candida endocarditis has changed
      dramatically with the use of antifungal therapy alone or in combination with
      surgery. Our case re-emphasizes the role of valve-sparing debridement with repair
      of the native valve using autologous pericardium in combination with long-term
      antifungal therapy as a feasible option in managing tricuspid valve Candida
      endocarditis.

PMID- 24116857
TI  - Suppression of surgeons' bacterial hand flora during surgical procedures with a
      new antimicrobial surgical glove.
AB  - BACKGROUND: Perforations of surgical gloves are common and increase with the
      duration of glove wear. Skin flora, re-grown after pre-operative disinfection of
      the hands, may contaminate a surgical site. An antimicrobial surgical glove with
      chlorhexidine on its inner surface has been developed. We hypothesized that by
      suppressing the re-growth of skin flora during the complete course of a surgical
      procedure, antimicrobial gloves may reduce the risk of surgical site
      contamination in the event of an intra-operative glove breach. METHODS: We
      conducted a randomized, double-blind, single-center trial, to measure any
      differences in the bacterial skin populations of surgeons' hands during surgical
      procedures done with antimicrobial and non-antimicrobial surgical gloves
      [ISRCTN71391952]. In this study, 25 pairs of gloves were retrieved from 14
      surgeons who donned them randomly on their dominant or non-dominant hand. The
      number of bacteria retrieved from glove fluid was measured and expressed as
      colony forming units (CFU)/mL. RESULTS: The median cfu/mL of antimicrobial gloves
      was 0.00 (LQ: 0.00 CFU/mL; UQ: 0.00 cfu/mL), with a mean log10 cfu/mL=0.02
      (range: 0.00-0.30). The median CFU/mL of non-antimicrobial gloves was 54.00 (LQ:
      3.00 cfu/mL; UQ: 100.00 cfu/mL) with a mean log10 CFU/mL=1.32 (range: 0.00-2.39).
      After a mean operating time of 112 min, the difference in the log10 CFU/mL was
      1.30 (p<0.001). CONCLUSIONS: A new antimicrobial surgical glove suppressed
      surgeons' hand flora during operative procedures. In the event of a glove breach,
      the use of such a glove may have the potential to prevent bacterial contamination
      of a sterile surgical site, thereby decreasing the risk of surgical site
      infection (SSI) and increasing patient safety. Further clinical studies are
      needed to confirm this concept.

PMID- 24116858
TI  - Acute cholecystitis with bacteremia caused by Pasteurella multocida.
AB  - BACKGROUND: Pasteurella multocida is a commensal organism present in the oral
      cavities of many animals. It can cause various infections including soft tissue,
      joint, and respiratory infections in human beings, but intra-abdominal infection
      by P. multocida is rare. We report our experience with a case of acute
      cholecystitis with bacteremia caused by P. multocida. CASE REPORT: The patient
      was a 39-year-old female who underwent emergency laparoscopic cholecystectomy for
      acute cholecystitis. The patient's blood and bile cultures were positive for P.
      multocida. She kept a dog and a cat as pets, but denied having had any bites or
      major scratches. Our investigation did not find that she had any sign of other
      potential sources of infection. CONCLUSION: Acute cholecystitis can be a primary
      source of Pasteurella bacteremia in a previously healthy, young patient.

PMID- 24116859
TI  - Reply to Comment on: Rural Generalism and the Queensland Health pathway -
      implications for rural clinical supervisors, placements and rural medical
      education providers.

PMID- 24116861
TI  - Distinctions between sluggish cognitive tempo, ADHD-IN, and depression symptom
      dimensions in Spanish first-grade children.
AB  - The objective of this study was to evaluate the validity of a new parent rating
      scale of Sluggish Cognitive Tempo (SCT). SCT was defined with 10 symptom domains-
      daydreams; attention fluctuates; absentminded; loses train of thought; easily
      confused; seems drowsy; thinking is slow; slow-moving; low initiative; and easily
      bored, needs stimulation--with each domain represented by multiple examples.
      Mothers' and fathers' ratings of SCT, ADHD-IN, ADHD-HI, oppositional defiant
      disorder (ODD), and depression symptoms along with ratings of academic and social
      impairment were obtained for a sample of 802 Spanish first-grade children (54%
      boys). SCT Symptom Domains 4 to 8 showed substantial loadings on the SCT factor
      (i.e., convergent validity) and substantially higher loadings on the SCT factor
      than the ADHD-IN factor (i.e., discriminant validity). This 5-domain measure of
      SCT showed good interrater and test-retest reliability for a 6-week interval.
      Higher scores on the 5-domain measure of SCT predicted higher levels of academic
      and social impairment even after controlling for ADHD-IN and depression. In
      contrast, higher levels of SCT were not uniquely related (or uniquely negatively
      related) to ADHD-HI and ODD, whereas ADHD-IN and depression were uniquely
      positively related to ADHD-HI and ODD. The new measure of SCT more clearly
      establishes that SCT, ADHD-IN, and depression represent independent symptom
      dimensions, thus providing a measurement tool to help determine if SCT and ADHD
      IN dimensions have unique biological correlates and if SCT and ADHD meet the
      criteria for different disorders.

PMID- 24116862
TI  - Treating sickle cell anaemia with hydroxycarbamide.

PMID- 24116860
TI  - Increase in prominence of electrocardiographic J waves after a single dose of
      propofol in a patient with early ventricular repolarisation.
AB  - J waves appear on an electrocardiogram as an elevation of the J point in the
      terminal portion of the QRS complex. J waves are often benign, but may be
      associated with malignant ventricular arrhythmias. In some cases, such problems
      appear to have been precipitated by propofol infusions. We observed a sudden
      increase in J waves and profound hypotension following a single intravenous dose
      of propofol in an 84-year-old woman with early repolarisation in the inferior
      ventricular wall. When early repolarisation (as shown by electrocardiographic J
      waves) is observed in the inferior ventricular wall pre-operatively, patients
      should be carefully monitored. Myocardial ischaemia and the use of drugs that
      might worsen J waves should be avoided. 

PMID- 24116863
TI  - Diagnostic stages of the parasites of the Florida manatee, Trichechus manatus
      latirostris.
AB  - Limited information is available on diagnostic stages of parasites in Florida
      manatees (Trichechus manatus latirostris). We examined 67 fecal samples from
      captive and wild manatees to define the diagnostic stages of the parasite fauna
      known to occur in Florida manatees. Parasite eggs were freshly extracted ex utero
      from identified mature helminths and subsequently characterized, illustrated, and
      matched to those isolated from fecal samples. In addition, coccidian oocysts in
      the fecal samples were identified. These diagnostic stages included eggs from 5
      species of trematodes (Chiorchis fabaceus, Chiorchis groschafti, Pulmonicola
      cochleotrema, Moniligerum blairi, and Nudacotyle undicola), 1 nematode
      (Heterocheilus tunicatus), and oocysts of 2 coccidians (Eimeria manatus and
      Eimeria nodulosa).

PMID- 24116864
TI  - A cohort study on full breastfeeding and child neuropsychological development:
      the role of maternal social, psychological, and nutritional factors.
AB  - AIM: This study investigated whether duration of full breastfeeding is associated
      with child neuropsychological development and whether this association is
      explained by social, psychological, and nutritional factors within families.
      METHOD: Participants in this study were a population-based birth cohort in the
      city of Sabadell (Catalonia, Spain). Females were recruited during the first
      trimester of pregnancy between July 2004 and July 2006. Information about
      parental characteristics and breastfeeding was obtained through questionnaires.
      Full breastfeeding was categorized as never, short term (<=4mo), long term (4
      6mo), or very long term (>6mo). A trained psychologist assessed the
      neuropsychological development of children at 4 years of age (n=434) using the
      McCarthy Scales of Children's Abilities (MSCA). RESULTS: Full breastfeeding
      showed an independent association with child general MSCA scores after adjusting
      for a range of social, psychological, and nutritional factors (>6mo,
      coefficient=7.4 [95% confidence interval=2.8-12.0], p=0.011). Maternal social
      class, education level, and IQ were also associated with child neuropsychological
      scores, but did not explain breastfeeding associations. Omega-3 (n3) fatty acid
      levels were not associated with child neuropsychological scores. INTERPRETATION:
      Very long-term full breastfeeding was independently associated with
      neuropsychological functions of children at 4 years of age. Maternal indicators
      of intelligence, psychopathology, and colostrum n3 fatty acids did not explain
      this association.

PMID- 24116865
TI  - Comparison of acute effect of systemic versus intravitreal infliximab treatment
      in an experimental model of endotoxin-induced uveitis.
AB  - PURPOSE: In this study, we investigated the efficacy of systemic and intravitreal
      (IV) infliximab treatments and compared these 2 different treatment modalities in
      an experimental model of endotoxin-induced uveitis (EIU). METHODS: Twenty-four
      white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV
      injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and
      saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4
      received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined
      with objective and subjective tests. The subjective test was clinical
      determination of uveitis, the objective tests were determination of protein
      concentrations and tumor necrosis factor alpha (TNF-alpha) levels and
      histopathology. RESULTS: Clinical examination score was lower in group 3 and
      group 4 (4+/-0.6 and 3.5+/-1.6, respectively) when compared with group 1 (P=0.02;
      P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous
      protein and TNF-alpha concentration measured significantly lower than group 1 and
      2. In histopathologic examination, there was no statistically significant
      difference between group 1, 2, and 3 (3.5+/-0.5, 3.6+/-0.5, 3.6+/-0.5,
      respectively). However, the lowest histopathologic inflammation was determined in
      group 4 (2.5+/-0.5) (compared with group 1 and group 3, respectively; P=0.03;
      P=0.014). CONCLUSION: In a rabbit model of experimental EIU, intravenous
      administration of infliximab was more effective than IV route in an acute period.

PMID- 24116866
TI  - Kinetic isotope effects support the twisted amide mechanism of Pin1 peptidyl
      prolyl isomerase.
AB  - The Pin1 peptidyl-prolyl isomerase catalyzes isomerization of pSer/pThr-Pro
      motifs in regulating the cell cycle. Peptide substrates, Ac-Phe-Phe-phosphoSer
      Pro-Arg-p-nitroaniline, were synthesized in unlabeled form, and with deuterium
      labeled Ser-d3 and Pro-d7 amino acids. Kinetic data were collected as a function
      of Pin1 concentration to measure kinetic isotope effects (KIEs) on catalytic
      efficiency (kcat/Km). The normal secondary (2 degrees ) KIE value measured for
      the Ser-d3 substrate (kH/kD = 1.6 +/- 0.2) indicates that the serine carbonyl
      does not rehybridize from sp(2) to sp(3) in the rate-determining step, ruling out
      a nucleophilic addition mechanism. The normal 2 degrees  KIE can be explained by
      hyperconjugation between Ser alpha-C-H/D and C?O and release of steric strain
      upon rotation of the amide bond from cis to syn-exo. The inverse 2 degrees  KIE
      value (kH/kD = 0.86 +/- 0.08) measured for the Pro-d7 substrate indicates
      rehybridization of the prolyl nitrogen from sp(2) to sp(3) during the rate
      limiting step of isomerization. No solvent kinetic isotope was measured by NMR
      exchange spectroscopy (kH2O/kD2O = 0.92 +/- 0.12), indicating little or no
      involvement of exchangeable protons in the mechanism. These results support the
      formation of a simple twisted amide transition state as the mechanism for
      peptidyl prolyl isomerization catalyzed by Pin1. A model of the reaction
      mechanism is presented using crystal structures of Pin1 with ground state
      analogues and an inhibitor that resembles a twisted amide transition state.

PMID- 24116867
TI  - VB-201, an oxidized phospholipid small molecule, inhibits CD14- and Toll-like
      receptor-2-dependent innate cell activation and constrains atherosclerosis.
AB  - Atherosclerosis is an inflammatory disease of the vascular wall. Activated
      monocytes and dendritic cells (DC) in the intima layer of the vasculature promote
      atherogenesis. Toll-like receptor (TLR)-2 and TLR-4, which are predominantly
      expressed on these cells and mediate their activation, are essential for
      atherosclerosis development. In this study we demonstrate that VB-201, an
      oxidized phospholipid (Ox-PL) small molecule, inhibits TLR signalling restricted
      to TLR-2 and TLR-4 in human and mouse monocytes and DC. Mechanistically, we show
      that VB-201 binds directly to TLR-2 and CD14, the TLR-4 co-receptor, to impair
      downstream cues and cytokine production. In a rabbit model, oral administration
      of VB-201 constrained atherosclerosis progression. This effect was not due to
      reduced cholesterol abundance, as hyperlipidaemia was sustained. We suggest that
      VB-201 may counter inflammation where TLR-2 and/or CD14 complicity is essential,
      and is therefore beneficial for the treatment of atherosclerosis.

PMID- 24116869
TI  - Synthesis and surface modification of mesoporous silica nanoparticles and its
      application as carriers for sustained drug delivery.
AB  - High drug loading is one of the important issues in the drug delivery research,
      especially the drug delivery system by oral administration. If high drug loading
      carriers are utilized the times of drug intake could be significantly reduced.
      Accordingly in this study, ordered mesoporous SBA-15 modified with (3
      aminopropyl) triethoxysilane (APTES) was used as a carrier for nonsteroidal anti
      inflammatory drug and optimization of the loading process was done. SBA-15 silica
      material with rope-like morphology was synthesized and modified by post-synthesis
      method with APTES. The synthesized SBA-15 and modified SBA-15 were characterized
      by XRD, SEM, thermal analysis and FT-IR spectroscopy. Loading optimization
      experiments were performed by changing the factors affecting the drug loading,
      such as temperature, time, stirring rate, Ibuprofen/SBA-15 ratio. The results of
      drug delivery experiments showed that the surface modification of SBA-15 with
      amino groups significantly increases the drug loading and decreases the drug
      delivery rate.

PMID- 24116870
TI  - Comparison of melanoma guidelines in the U.S.A., Canada, Europe, Australia and
      New Zealand: a critical appraisal and comprehensive review.
AB  - There are several well-established guidelines for the staging of melanoma and the
      size of excisional margins, along with recommendations for sentinel lymph node
      biopsy. Guidelines have been proposed in the U.S.A. (National Comprehensive
      Cancer Network), Canada (Cancer Care Ontario and Canadian Medical Association),
      Europe (European Society for Medical Oncology) and Australia and New Zealand
      (Australian Cancer Network). The guidelines set by these groups are largely based
      on current evidence, or expert panel consensus where evidence is lacking. The
      recommendations are more controversial and varying where there is a lack of level
      one evidence in the literature (e.g. screening, adjuvant therapy, follow-up
      intensity). We review the evidence and available literature for the management of
      melanoma worldwide. 

PMID- 24116871
TI  - The size is not important.

PMID- 24116868
TI  - One-year safety and efficacy of ustekinumab and results of dose adjustment after
      switching from inadequate methotrexate treatment: the TRANSIT randomized trial in
      moderate-to-severe plaque psoriasis.
AB  - BACKGROUND: There are limited long-term, 'real-world' data on ustekinumab, or the
      effect of dose adjustment in suboptimal responders. OBJECTIVES: We describe 52
      week data from TRANSIT, which initiated ustekinumab by licensed regimen and
      investigated exploratory dose adjustment. METHODS: Patients with moderate-to
      severe psoriasis and inadequate methotrexate response received ustekinumab, with
      immediate or gradual methotrexate withdrawal. Outcomes were similar between
      treatment arms at week 12 (primary endpoint), so week 52 data were pooled.
      Patients weighing <= 100 kg or > 100 kg were administered ustekinumab 45 or 90
      mg, respectively. Patients weighing <= 100 kg without 75% improvement in
      Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a
      dose adjustment to 90 mg. The primary analysis used observed data. RESULTS:
      Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively.
      Forty-four patients (9%) discontinued before week 52 (0.4% due to adverse
      events). At week 52 (in the overall population), 369 patients (83%) achieved a
      PASI score <= 5, and 341 patients (77%) achieved PASI 75; the median PASI score
      decreased from 15 at baseline to 1.8. At weeks 28 and 40, 84 and 31 patients,
      respectively, did not achieve PASI 75 and received a dose adjustment; by week 52,
      35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75
      (two discontinued between weeks 28 and 40). CONCLUSIONS: Ustekinumab showed
      sustained 1-year efficacy and was well tolerated when initially administered
      according to label. Adjusting the ustekinumab dose to 90 mg may result in
      clinically meaningful improvement in response in patients weighing <= 100 kg with
      suboptimal initial response.

PMID- 24116872
TI  - Assessing the impact of chlorinated-solvent sites on metropolitan groundwater
      resources.
AB  - Chlorinated-solvent compounds are among the most common groundwater contaminants
      in the United States. A majority of the many sites contaminated by chlorinated
      solvent compounds are located in metropolitan areas, and most such areas have one
      or more chlorinated-solvent contaminated sites. Thus, contamination of
      groundwater by chlorinated-solvent compounds may pose a potential risk to the
      sustainability of potable water supplies for many metropolitan areas. The impact
      of chlorinated-solvent sites on metropolitan water resources was assessed for
      Tucson, Arizona, by comparing the aggregate volume of extracted groundwater for
      all pump-and-treat systems associated with contaminated sites in the region to
      the total regional groundwater withdrawal. The analysis revealed that the
      aggregate volume of groundwater withdrawn for the pump-and-treat systems
      operating in Tucson, all of which are located at chlorinated-solvent contaminated
      sites, was 20% of the total groundwater withdrawal in the city for the study
      period. The treated groundwater was used primarily for direct delivery to local
      water supply systems or for reinjection as part of the pump-and-treat system. The
      volume of the treated groundwater used for potable water represented
      approximately 13% of the total potable water supply sourced from groundwater, and
      approximately 6% of the total potable water supply. This case study illustrates
      the significant impact chlorinated-solvent contaminated sites can have on
      groundwater resources and regional potable water supplies. 

PMID- 24116873
TI  - Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme
      selectivity.
AB  - Tankyrases are ADP-ribosyltransferases that play key roles in various cellular
      pathways, including the regulation of cell proliferation, and thus, they are
      promising drug targets for the treatment of cancer. Flavones have been shown to
      inhibit tankyrases and we report here the discovery of more potent and selective
      flavone derivatives. Commercially available flavones with single substitutions
      were used for structure-activity relationship studies, and cocrystal structures
      of the 18 hit compounds were analyzed to explain their potency and selectivity.
      The most potent inhibitors were also tested in a cell-based assay, which
      demonstrated that they effectively antagonize Wnt signaling. To assess
      selectivity, they were further tested against a panel of homologous human ADP
      ribosyltransferases. The most effective compound, 22 (MN-64), showed 6 nM potency
      against tankyrase 1, isoenzyme selectivity, and Wnt signaling inhibition. This
      work forms a basis for rational development of flavones as tankyrase inhibitors
      and guides the development of other structurally related inhibitors. 

PMID- 24116874
TI  - BRCA1 and BRCA2 - update and implications on the genetics of breast cancer: a
      clinical perspective.

PMID- 24116875
TI  - Biosynthetic support based on dendritic poly(L-lysine) improves human skin
      fibroblasts attachment.
AB  - Poly(L-lysine) (PLL) dendrigrafts (DGLs) are arborescent biosynthetic polymers of
      regular and controlled structures. They have specific properties such as
      biocompatibility and non-immunogenicity, and their surface density of NH2
      functions can be easily modified and therefore appears as a powerful tool for the
      functionalization of hydrophobic polymers used in the context of tissue
      engineering. In this study, we evaluated several criteria of human skin
      fibroblasts when cultured with DGL of generations 2, 3 and 4, with linear PLL
      polymer as reference. In aqueous phase, DGLs and PLL displayed a similar
      cytotoxicity towards fibroblasts. Plastic culture plates grafted with DGLs were
      further characterized as homogeneous surfaces by atomic force microscopy and
      surface characterization by amino density estimation by colorimetric assay.
      Proliferation of fibroblasts was increased when cultured onto PLL and DGLs
      monolayers when compared with crude plates. Cellular adhesion was increased by
      20% on DGLs in comparison to PLL. Integrin alpha5 subunit protein expression
      level was increased after 48 h of culture on DGLs, in comparison to control or
      PLL-coated surfaces. The presence of DGLs did not lead to overexpression or
      activation of matrix metalloproteinases 2 and 9. Finally, fibroblasts adhesion
      was increased by 40% on poly-(lactic-co-glycolic acid) matrices functionalized
      with DGLs when compared to PLL. Overall, these features make DGL promising
      candidates for the surface engineering of biomaterials in tissue engineering.

PMID- 24116876
TI  - Confining the nucleation and overgrowth of Rh to the {111} facets of Pd
      nanocrystal seeds: the roles of capping agent and surface diffusion.
AB  - This article describes a systematic study of the spatially confined growth of Rh
      atoms on Pd nanocrystal seeds, with a focus on the blocking effect of a surface
      capping agent and the surface diffusion of adatoms. We initially used Pd
      cuboctahedrons as the seeds to illustrate the concept and to demonstrate the
      capabilities of our approach. Because the Pd{100} facets were selectively capped
      by a layer of chemisorbed Br(-) or I(-) ions, we were able to confine the
      nucleation and deposition of Rh atoms solely on the {111} facets of a Pd seed.
      When the synthesis was conducted at a relatively low temperature, the deposition
      of Rh atoms followed an island growth mode because of the high Rh-Rh interatomic
      binding energy. We also facilitated the surface diffusion of deposited Rh atoms
      by increasing the reaction temperature and decreasing the injection rate for the
      Rh precursor. Under these conditions, the deposition of Rh on the Pd{111} facets
      was switched to a layered growth mode. We further successfully extended this
      approach to a variety of other types of Pd polyhedral seeds that contained
      Pd{111} and Pd{100} facets in different proportions on the surface. As expected,
      a series of Pd-Rh bimetallic nanocrystals with distinctive elemental
      distributions were obtained. We could remove the Pd cores through selective
      chemical etching to generate Rh hollow nanoframes with different types and
      degrees of porosity. This study clearly demonstrates the importance of facet
      capping, surface diffusion, and reaction kinetics in controlling the morphologies
      of bimetallic nanocrystals during a seed-mediated process. It also provides a new
      direction for the rational design and synthesis of nanocrystals with spatially
      controlled distributions of elements for a variety of applications.

PMID- 24116878
TI  - Clinically significant effects of group cognitive behavioral therapy on spouse
      caregivers' mental health and cognitive functioning: a pilot study.
AB  - The objective of this pilot study was to investigate whether group cognitive
      behavioral therapy (CBT) resulted in clinically meaningful improvements in
      caregiver mood, burden, and cognition. We screened 97 caregivers in Toronto,
      Canada, of whom 25 with DSM-IV disorders began the 13-week CBT intervention, and
      12 completed therapy and the 3-month follow-up. Each caregiver experienced
      clinically significant improvement on at least 2 of the following outcomes:
      diagnostic criteria, mood, attention, memory, and caregiver burden. Despite
      effectiveness, the challenges of recruiting distressed caregivers for therapy
      suggest that CBT might be most useful as part of a stepped care model of
      treatment. 

PMID- 24116879
TI  - Construction of hetero[n]rotaxanes by use of polyfunctional rotaxane frameworks.
AB  - Heterorotaxanes, one class of topological organic structures, have attracted
      increasing interesting during the past two decades. In general, two types of
      heterorotaxane structures exist, one in which two or more different macrocycles
      are threaded onto one dumbbell-shaped molecule and the other where one macrocycle
      is threaded onto two or more different dumbbell-shaped molecules. In comparison
      to these traditional types, another family of topologically interesting
      heterorotaxanes can be envisaged as arising from polyfunctional molecules that
      possess both host (crown ether) and guest (ammonium templates). In the present
      investigation, we have explored the construction of selected members of this new
      heterorotaxane family, which possess crown ether moieties that are wrapped around
      a dumbbell-shaped molecule. These structures are prepared by routes in which
      "stitching" processes, involving template-directed clipping reaction or olefin
      metathesis reactions, are used to install crown ether ring systems encircling
      ammonium cation centers. This is then followed by implementation of a threading
      followed-by-stoppering sequence to install a second encircling crown ether ring.
      The results show that the polyfunctional building blocks assemble with high
      efficiencies. Finally, this investigation provides a foundation for future
      studies aimed at constructing more complicated heterorotaxane architectures, such
      as switchable systems, self-assembling polymers, and functional molecular
      machines. 

PMID- 24116877
TI  - Clinical features, proximate causes, and consequences of active convulsive
      epilepsy in Africa.
AB  - PURPOSE: Epilepsy is common in sub-Saharan Africa (SSA), but the clinical
      features and consequences are poorly characterized. Most studies are hospital
      based, and few studies have compared different ecological sites in SSA. We
      described active convulsive epilepsy (ACE) identified in cross-sectional
      community-based surveys in SSA, to understand the proximate causes, features, and
      consequences. METHODS: We performed a detailed clinical and neurophysiologic
      description of ACE cases identified from a community survey of 584,586 people
      using medical history, neurologic examination, and electroencephalography (EEG)
      data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana.
      The cases were examined by clinicians to discover risk factors, clinical
      features, and consequences of epilepsy. We used logistic regression to determine
      the epilepsy factors associated with medical comorbidities. KEY FINDINGS: Half
      (51%) of the 2,170 people with ACE were children and 69% of seizures began in
      childhood. Focal features (EEG, seizure types, and neurologic deficits) were
      present in 58% of ACE cases, and these varied significantly with site. Status
      epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic
      drugs (phenobarbital was the most common drug [95%]), and the proportion varied
      significantly with the site. Proximate causes of ACE were adverse perinatal
      events (11%) for onset of seizures before 18 years; and acute encephalopathy
      (10%) and head injury prior to seizure onset (3%). Important comorbidities were
      malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%).
      The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack
      of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all
      significantly more common than in those without epilepsy. SIGNIFICANCE: There
      were significant differences in the comorbidities across sites. Focal features
      are common in ACE, suggesting identifiable and preventable causes. Malnutrition
      and cognitive and neurologic deficits are common in people with ACE and should be
      integrated into the management of epilepsy in this region. Consequences of
      epilepsy such as burns, lack of education, poor marriage prospects, and
      unemployment need to be addressed.

PMID- 24116880
TI  - Exploring the benefits of unilateral nostril breathing practice post-stroke:
      attention, language, spatial abilities, depression, and anxiety.
AB  - OBJECTIVE: Unilateral nostril breathing (UNB) is a yogic pranayama technique that
      has been shown to improve verbal and spatial cognition in neurologically intact
      individuals. Early study of UNB in healthy individuals has shown benefits for
      attention and memory. This preliminary study explored whether UNB influenced
      various measures of attention, language, spatial abilities, depression, and
      anxiety in post-stroke individuals, both with and without aphasia. DESIGN: A
      within-subjects repeated-measures design was used to determine whether UNB
      improved cognitive, linguistic, and affect variables in post-stroke individuals.
      Within-subjects comparisons determined UNB's effects over time, and between
      subjects comparison was used to determine whether changes in these variables
      differed between post-stroke individuals with and without aphasia. SETTING:
      Athens and Atlanta, Georgia. PARTICIPANTS: Eleven post-stroke individuals
      participated in a 10-week UNB program. Five individuals had stroke-induced left
      hemisphere damage with no diagnosis of aphasia (left hemisphere damage control
      group; LHD), and six individuals experienced left hemisphere damage with a
      diagnosis of aphasia (individuals with aphasia group; IWA). MEASURES: Individuals
      were assessed on measures of attention, language, spatial abilities, depression,
      and anxiety before, during, and after UNB treatment. RESULTS: UNB significantly
      decreased levels of anxiety for individuals in both groups. Performance on
      language measures increased for the individuals with aphasia. CONCLUSIONS:
      Significant findings for language and affect measures indicate that further
      investigation regarding duration of UNB treatment and use of UNB treatment
      alongside traditional speech-language therapy in post-stroke individuals is
      warranted.

PMID- 24116881
TI  - Treatment of low back pain: the potential clinical and public health benefits of
      topical herbal remedies.

PMID- 24116882
TI  - A highly selective fluorescence "turn-on" probe for Cu(II) based on reaction and
      its imaging in living cells.
AB  - A new oxidative C-O bond cleavage reaction-based probe FluHMPP was designed and
      prepared. FluHMPP displays excellent selective turn-on fluorescence response for
      Cu(II) in aqueous solution under visible light excitation. The cleavage products
      are fully characterized. Fluorescein fragment is further oxidized to highly
      fluorescent MFME (3'-O-methylfluorescein methyl ester), and benzyl ether of imine
      fragment has been transformed to carboxyl. Confocal microscopy experiments have
      demonstrated that FluHMPP could also be used in live cells for the detection of
      Cu(II). 

PMID- 24116883
TI  - The bench is the bedside - the role of transthoracic echocardiography in
      translating pregnancy research into clinical practice.

PMID- 24116884
TI  - Automated external defibrillators are not always located to meet the need.

PMID- 24116885
TI  - Simultaneous conditioning of valence and arousal.
AB  - Evaluative conditioning (EC) refers to the change in the valence of a conditioned
      stimulus (CS) due to its pairing with a positive or negative unconditioned
      stimulus (US). To the extent that core affect can be characterised by the two
      dimensions of valence and arousal, EC has important implications for the origin
      of affective responses. However, the distinction between valence and arousal is
      rarely considered in research on EC or conditioned responses more generally.
      Measuring the subjective feelings elicited by a CS, the results from two
      experiments showed that (1) repeated pairings of a CS with a positive or negative
      US of either high or low arousal led to corresponding changes in both CS valence
      and CS arousal, (2) changes in CS arousal, but not changes in CS valence, were
      significantly related to recollective memory for CS-US pairings, (3) subsequent
      presentations of the CS without the US reduced the conditioned valence of the CS,
      with conditioned arousal being less susceptible to extinction and (4) EC effects
      were stronger for high arousal than low arousal USs. The results indicate that
      the conditioning of affective responses can occur simultaneously along two
      independent dimensions, supporting evidence in related areas that calls for a
      consideration of both valence and arousal. Implications for research on EC and
      the acquisition of emotional dispositions are discussed. 

PMID- 24116886
TI  - Comparison of strategies to increase HIV testing among African-American gay,
      bisexual, and other men who have sex with men in Washington, DC.
AB  - This paper presents results from a study conducted to compare the relative
      effectiveness of three strategies - alternate venue testing (AVT), the social
      network strategy (SNS), and partner counseling and referral services (PCRS;
      standard care) - for reaching and motivating previously undiagnosed, African
      American men who have sex with men (AA MSM) to be tested for HIV. Data were
      collected between June 2008 and February 2010 at a gay-identified, community
      based organization (CBO) serving AA MSM in Washington, DC. Men were eligible to
      participate if they were 18-64 years old, self-identified as black or African
      American, were biologically male, and self-reported oral or anal sex with a man
      in the past six months. Fisher's exact test of independence was used to assess
      differences in demographics, testing history, HIV status and sexual behaviors
      across the three strategies. The final sample included 470 men who met all
      eligibility requirements. There were no statistically significant differences in
      HIV positivity rates across the three strategies. However, relative to standard
      care, the SNS, and (to a lesser degree) the AVT strategies were more successful
      in recruiting men that had never been tested. Additionally, the results indicate
      that each strategy recruited different subgroups of men. Specifically,
      heterosexually identified men and men who reported engaging in unprotected sex
      were most likely to be recruited via SNS. Bisexually identified men and older men
      were most likely to be recruited via AVT or SNS, while standard care tended to
      reach greater proportions of young men and homosexually identified men. These
      findings suggest that a combination of strategies may be the best approach for
      engaging African-American MSM in HIV testing. 

PMID- 24116887
TI  - Prosociality and negative emotionality mediate the association of serotonin
      transporter genotype with childhood ADHD and ODD.
AB  - Although there is evidence that the promoter polymorphism of the serotonin
      transporter (5-HTTLPR) gene is associated with attention-deficit/hyperactivity
      disorder (ADHD) and oppositional defiant disorder (ODD), the pathways underlying
      these associations are largely unknown. Given their theoretical and biological
      plausibility, we tested whether individual differences in key temperament
      dimensions (i.e., prosociality, negative emotionality, daring) constituted
      potential pathways from 5-HTTLPR to ADHD and ODD. Using a well-characterized
      sample of 194 six to nine-year-old children with and without ADHD, we utilized
      multiple mediation procedures with bootstrapping to evaluate prosociality,
      negative emotionality, and daring as independent mediators of 5-HTTLPR with
      separate parent and teacher ratings of ADHD and ODD. Controlling for ODD,
      prosociality and negative emotionality significantly mediated the association of
      5-HTTLPR and parent-reported ADHD. Similarly, controlling for ADHD, prosociality
      and negative emotionality each uniquely mediated the association of 5-HTTLPR and
      parent-reported ODD. For teacher-reported ADHD, prosociality significantly
      mediated the association of 5-HTTLPR (controlling for ODD) whereas controlling
      for ODD, negative emotionality significantly mediated the prediction of teacher
      reported ODD from 5-HTTLPR. Specifically, the number of 5-HTTLPR long alleles was
      inversely associated with prosociality and positively associated with negative
      emotionality; prosociality was inversely associated and negative emotionality was
      positively associated with ADHD and ODD. We consider the role of temperament in
      genetically sensitive designs as well as its potential value in the development
      and delivery of effective interventions. 

PMID- 24116888
TI  - Reply to comments by Dr. Brind and Mr. Carroll on our study No evidence of an
      association between induced abortion and breast cancer among parous older women:
      our conclusion remains valid.

PMID- 24116889
TI  - Retracted: Post-stroke epilepsy in Polish paediatric patients.
AB  - The above article, published online on 5 October 2013 in Wiley Online Library
      Early View (http://onlinelibrary.wiley.com/), has been retracted by agreement
      between the authors, the journal Editor in Chief, Dr Peter Baxter, and John Wiley
      & Sons Ltd. The retraction has been agreed due to several errors in the
      statistics. These errors make interpretation of the data difficult and the
      validity of the conclusions questionable. 

PMID- 24116890
TI  - Can we switch microglia's phenotype to foster neuroprotection? Focus on multiple
      sclerosis.
AB  - Microglia cells, the resident innate immune cells in the brain, are highly
      active, extending and retracting highly motile processes through which they
      continuously survey their microenvironment for 'danger signals' and interact
      dynamically with surrounding cells. Upon sensing changes in their central nervous
      system microenvironment, microglia become activated, undergoing morphological and
      functional changes. Microglia activation is not an 'all-or-none' process, but
      rather a continuum depending on encountered stimuli, which is expressed through a
      spectrum of molecular and functional phenotypes ranging from so-called
      'classically activated', with a highly pro-inflammatory profile, to
      'alternatively activated' associated with a beneficial, less inflammatory,
      neuroprotective profile. Microglia activation has been demonstrated in most
      neurological diseases of diverse aetiology and has been implicated as a
      contributor to neurodegeneration. The possibility to promote microglia's
      neuroprotective phenotype has therefore become a therapeutic goal. We have
      focused our discussion on the role of microglia in multiple sclerosis, a
      prototype of inflammatory, demyelinating, neurodegenerative disease, and on the
      effect of currently approved or on-trial anti-inflammatory therapeutic strategies
      that might mediate neuroprotection at least in part through their effect on
      microglia by modifying their behaviour via a switch of their functional phenotype
      from a detrimental to a protective one. In addition to pharmaceutical approaches,
      such as treatment with glatiramer acetate, interferon-beta, fingolimod or
      dimethyl fumarate, we address the alternative therapeutic approach of treatment
      with mesenchymal stem cells and their potential role in neuroprotection through
      their 'calming' effect on microglia.

PMID- 24116891
TI  - Novel analogues of chlormethiazole are neuroprotective in four cellular models of
      neurodegeneration by a mechanism with variable dependence on GABA(A) receptor
      potentiation.
AB  - BACKGROUND AND PURPOSE: Chlormethiazole (CMZ), a clinical sedative/anxiolytic
      agent, did not reach clinical efficacy in stroke trials despite neuroprotection
      demonstrated in numerous animal models. Using CMZ as a lead compound,
      neuroprotective methiazole (MZ) analogues were developed, and neuroprotection and
      GABA(A) receptor dependence were studied. EXPERIMENTAL APPROACH: Eight MZs were
      selected from a novel library, of which two were studied in detail.
      Neuroprotection, glutamate release, intracellular calcium and response to GABA
      blockade by picrotoxin were measured in rat primary cortical cultures using four
      cellular models of neurodegeneration. GABA potentiation was assayed in oocytes
      expressing the alpha1beta2gamma2 GABA(A) receptor. KEY RESULTS: Neuroprotection
      against a range of insults was retained even with substantial chemical
      modification. Dependence on GABAA receptor activity was variable: at the
      extremes, neuroprotection by GN-28 was universally sensitive to picrotoxin, while
      GN-38 was largely insensitive. In parallel, effects on extracellular glutamate
      and intracellular calcium were associated with GABA(A) dependence. Consistent
      with these findings, GN-28 potentiated alpha1beta2gamma2 GABA(A) function,
      whereas GN-38 had a weak inhibitory effect. Neuroprotection against moderate dose
      oligomeric Abeta1-42 was also tolerant to structural changes. CONCLUSIONS AND
      IMPLICATIONS: The results support the concept that CMZ does not contain a single
      pharmacophore, rather that broad-spectrum neuroprotection results from a GABA(A)
      dependent mechanism represented by GN-28, combined with a mechanism represented
      in GN-38 that shows the least dependence on GABA(A) receptors. These findings
      allow further refinement of the neuroprotective pharmacophore and investigation
      into secondary mechanisms that will assist in identifying MZ-based compounds of
      use in treating neurodegeneration.

PMID- 24116892
TI  - Secondary cancers among children with acute lymphoblastic leukaemia treated by
      the Tokyo Children's Cancer Study Group protocols: a retrospective cohort study.
AB  - With improvement in survival, it is important to evaluate the impact of treatment
      on secondary cancers in acute lymphoblastic leukaemia (ALL) survivors. A
      retrospective cohort study comprising 2918 children diagnosed with ALL and
      enrolled on Tokyo Children's Cancer Study Group (TCCSG) protocols between 1984
      and 2005 was conducted to evaluate the incidence of secondary cancers and
      associated factors including treatment protocol, cranial irradiation and other
      characteristics of the primary ALL. Thirty-seven patients developed secondary
      cancers, including acute myeloid leukaemia (n = 11), myelodysplastic syndrome (n
      = 5), non-Hodgkin lymphoma (n = 2), brain tumours (n = 13) and other solid
      carcinomas (n = 6) within a median follow-up duration of 9.5 years. The
      cumulative incidence of any secondary cancers was 1.0% (95% confidence interval
      (CI), 0.7-1.4%) at 10 years and 2.4% (95% CI, 1.5-3.7%) at 20 years,
      respectively. Standardized incidence rate ratio of secondary cancers was 9.3 (95%
      CI, 6.5-12.8). Multivariate analyses showed an increased risk of secondary
      cancers associated with the recent treatment protocol and cranial irradiation.
      There was no evidence of a reduction in secondary cancer incidence despite marked
      decreases in cranial irradiation use in the recent protocols. 

PMID- 24116894
TI  - It is my great pleasure to welcome you to the fourth issue of 2013. Editorial.

PMID- 24116893
TI  - Human T cell leukaemia virus type 2 tax protein mediates CC-chemokine expression
      in peripheral blood mononuclear cells via the nuclear factor kappa B canonical
      pathway.
AB  - Retroviral co-infections with human immunodeficiency virus type-1 (HIV-1) and
      human T cell leukaemia virus type 1 (HTLV-1) or type 2 (HTLV-2) are prevalent in
      many areas worldwide. It has been observed that HIV-1/HTLV-2 co-infections are
      associated with slower rates of CD4(+) T cell decline and delayed progression to
      AIDS. This immunological benefit has been linked to the ability of Tax2, the
      transcriptional activating protein of HTLV-2, to induce the expression of
      macrophage inflammatory protein (MIP)-1alpha/CCL3, MIP-1beta/CCL4 and regulated
      upon activation normal T cell expressed and secreted (RANTES)/CCL5 and to down
      regulate the expression of the CCR5 co-receptor in peripheral blood mononuclear
      cells (PBMCs). This study aimed to assess the role of Tax2-mediated activation of
      the nuclear factor kappa B (NF-kappaB) signalling pathway on the production of
      the anti-viral CC-chemokines MIP-1alpha, MIP-1beta and RANTES. Recombinant Tax1
      and Tax2 proteins, or proteins expressed via adenoviral vectors used to infect
      cells, were tested for their ability to activate the NF-kappaB pathway in
      cultured PBMCs in the presence or absence of NF-kappaB pathway inhibitors.
      Results showed a significant release of MIP-1alpha, MIP-1beta and RANTES by PBMCs
      after the activation of p65/RelA and p50. The secretion of these CC-chemokines
      was significantly reduced (P < 0.05) by canonical NF-kappaB signalling
      inhibitors. In conclusion, Tax2 protein may promote innate anti-viral immune
      responses through the activation of the canonical NF-kappaB pathway.

PMID- 24116895
TI  - Epilepsy in ring 14 syndrome: a clinical and EEG study of 22 patients.
AB  - PURPOSE: To characterize epileptic phenotype, electroencephalography (EEG)
      features, and epileptic evolution in patients with ring 14 r(14) syndrome.
      METHODS: Twenty-two patients with ring chromosome 14 were enrolled in the study.
      We examined age at onset, seizure semiology and frequency at onset and at follow
      up, drug responsiveness/resistance, and interictal/ictal EEG data. The degree of
      severity of the epileptic phenotype negatively influences child cognitive
      development. KEY FINDINGS: The incidence of epilepsy in patients with r(14)
      syndrome is virtually 100%, characterized by early onset, polymorphic seizures,
      and drug-resistant seizures. In addition, we ascertained focal secondarily
      generalized epilepsy, seizure cluster tendency, frequent status epilepticus, and
      a rather typical epilepsy evolution. EEG abnormalities consisted of slow
      background activity with pseudoperiodic bursts of generalized slow waves in the
      early stage, focal frontotemporal or temporoposterior slow waves with multifocal
      spikes interposed, and unusual rhythmic fast recruiting posterior spikes followed
      by secondary generalization. The degree of severity of the epileptic phenotype
      negatively influences child cognitive development. SIGNIFICANCE: This study
      provides a more precise definition of seizure types, natural history, and drug
      responsiveness of r(14) syndrome, a highly epileptogenic chromosomal condition.

PMID- 24116896
TI  - Comparative topical delivery of antifungal drug croconazole using liposome and
      micro-emulsion-based gel formulations.
AB  - The aim of this study was to develop liposomal-based (LBGF) and micro-emulsion
      based (MBGF) gel formulations of croconazole to compare their topical delivery
      potential. Conventional gels were also prepared using various polymers such as
      sodium carboxymethyl cellulose (SCMC), Poloxamer 407, Carbopol 971P and chitosan.
      The in vitro release of croconazole from conventional gel formulations, LBGF and
      MBGF were carried out using cellophane membrane as permeation membrane. However,
      in vitro skin permeations studies of all formulations were carried out using rat
      skin. The results of the drug release/skin permeation studies indicated that the
      highest release was obtained from SCMC followed by chitosan, Poloxamer 407 and
      finally Carbopol 971P gel. Therefore, liposomes and micro-emulsions were loaded
      on Carbopol 971P gel. The drug release and skin permeation of croconazole from
      different LBGF and MBGF showed that MBGF had superior release/permeation than
      LBGF. MBGF having ethanol as co-surfactant showed higher release/permeation of
      drug than MBGF-containing propylene glycol. The analysis of data according to
      different kinetic models indicated that the release of drug from different LBGF
      and MBGF followed the Higuchi model. The antimicrobial activity of the different
      LBGF and MBGF of croconazole was carried out by measuring the inhibition zone
      (mm) and compared by the effect of miconazole cream as control. The different
      LBGF and MBGF showed an excellent activity against different species of fungi as
      compared with miconazole cream. Overall, these results indicated that developed
      LBGF and MBGF could have great potential for topical delivery of croconazole.

PMID- 24116897
TI  - What are the supportive and palliative care needs of patients with cutaneous T
      cell lymphoma and their caregivers? A systematic review of the evidence.
AB  - BACKGROUND: Primary cutaneous T-cell lymphoma (CTCL) is progressive, can cause
      significant symptoms, and impacts on quality of life. Therefore supportive and
      palliative care might have a role in the care of patients and families.
      OBJECTIVES: To identify and appraise the available peer-reviewed evidence on the
      supportive and palliative care needs of patients and their caregivers. METHODS: A
      systematic review of the literature was conducted. Extracted data from eligible
      papers were collated in themes relating to supportive and palliative care needs
      and outcomes for patients, informal caregivers, health professionals and reported
      service models. RESULTS: Eighteen retained papers reported a symptom or quality
      of-life measure. Five reported only these measures, 13 reported outcomes in
      relation to an intervention. Systemic therapy targeted at disease remission was
      the most commonly reported intervention (12/13). No quality-of-life tool was
      consistently used. Pruritus was frequently reported as an outcome (n = 9) often
      using the visual analogue scale, VAS itch. Psychosocial, spiritual and caregiver
      needs were reported infrequently or not at all. CONCLUSIONS: No measure is
      routinely used to measure supportive and palliative care outcomes in CTCL.
      Physical needs, particularly pruritus, were reported commonly; however,
      qualitative evidence of experience is limited. Caregivers' needs are rarely
      explored. To compare outcomes from clinical studies, a single multidimensional
      tool used in routine practice would be useful. Further work is needed to explore
      a model of service that meets the specific physical, psychosocial and spiritual
      needs of this group of patients and their carers.

PMID- 24116898
TI  - Electrocatalytic hydrogen evolution from water by a series of iron carbonyl
      clusters.
AB  - The development of efficient hydrogen evolving electrocatalysts that operate near
      neutral pH in aqueous solution remains of significant interest. A series of low
      valent iron clusters have been investigated to provide insight into the structure
      function relationships affecting their ability to promote formation of cluster
      hydride intermediates and to promote electrocatalytic hydrogen evolution from
      water. Each of the metal carbonyl anions, [Fe4N(CO)12](-) (1(-)), [Fe4C(CO)12](2
      ) (2(2-)), [Fe5C(CO)15](2-) (3(2-)), and [Fe6C(CO)18](2-) (4(2-)) were isolated
      as their sodium salt to provide the necessary solubility in water. At pH 5 and 
      1.25 V vs SCE the clusters afford hydrogen with Faradaic efficiencies ranging
      from 53-98%. pH dependent cyclic voltammetry measurements provide insight into
      catalytic intermediates. Both of the butterfly shaped clusters, 1(-) and 2(2-),
      stabilize protonated adducts and are effective catalysts. Initial reduction of
      butterfly shaped 1(-) is pH-independent and subsequently, successive protonation
      events afford H1(-), and then hydrogen. In contrast, butterfly shaped 2(2-)
      undergoes two successive proton coupled electron transfer events to form H22(2-)
      which then liberates hydrogen. The higher nuclearity clusters, 3(2-) and 4(2-),
      do not display the same ability to associate with protons, and accordingly, they
      produce hydrogen less efficiently. 

PMID- 24116900
TI  - Efficient noble metal-free (electro)catalysis of water and alcohol oxidations by
      zinc-cobalt layered double hydroxide.
AB  - Replacing rare and expensive noble metal catalysts with inexpensive and earth
      abundant ones for various renewable energy-related chemical processes as well as
      for production of high value chemicals is one of the major goals of sustainable
      chemistry. Herein we show that a bimetallic Zn-Co layered double hydroxide (Zn-Co
      LDH) can serve as an efficient electrocatalyst and catalyst for water and alcohol
      oxidation, respectively. In the electrochemical water oxidation, the material
      exhibits a lower overpotential, by ~100 mV, than monometallic Co-based solid
      state materials (e.g., Co(OH)2 and Co3O4)-catalytic systems that were recently
      reported to be effective for this reaction. Moreover, the material's turnover
      frequency (TOF) per Co atoms is >10 times as high as those of the latter at the
      same applied potentials. The Zn-Co-LDH also catalyzes oxidation of alcohols to
      the corresponding aldehydes or ketones at relatively low temperature, with
      moderate to high conversion and excellent selectivity.

PMID- 24116899
TI  - Interplay of degradation, dissolution and stabilization of clarithromycin and its
      amorphous solid dispersions.
AB  - Clarithromycin (CLA) is an aminomacrolide antibiotic whose physical properties
      are fascinating and challenging. It has very poor solubility at neutral
      intestinal pH, but much better solubility under acidic conditions due to amine
      protonation. The improved solubility in an acid environment is confounded by the
      poor chemical stability of clarithromycin that is quite labile toward acid
      catalyzed degradation. This creates a complex system under gastrointestinal (GI)
      conditions: dissolution in the stomach, degradation, potential for precipitation
      in the small intestine, and interplay with the formulation components. We report
      herein a study of amorphous solid dispersion (ASD) of CLA with carboxyl
      containing cellulose derivatives, which have recently been shown to be excellent
      ASD matrices for maximizing oral bioavailability. This approach was intended to
      improve CLA solubility in neutral media while minimizing release in an acid
      environment, and thereby increase its uptake from the small intestine. Amorphous
      polymer/CLA nanoparticles were also prepared by high-shear mixing in a multi
      inlet vortex mixer (MIVM). Different extents of release were observed at low pH
      from the various formulations. Thus the solubility increase from nanosizing was
      deleterious to the concentration of intact CLA obtained upon reaching small
      intestine conditions; the high extent of release at gastric pH led to complete
      degradation of CLA. Using pH-switch experiments, it was possible to separate the
      effects of loss of CLA from solution by crystallization vs. that from chemical
      degradation. It was found that the hydrophobic cellulose derivative cellulose
      acetate adipate propionate (CAAdP) was effective at protecting CLA from
      dissolution in the stomach, and preventing CLA decomposition at low pH; 54% of
      CLA in CAADP ASD was released intact, vs. 0% and 6% from HPMCAS and CMCAB ASDs,
      respectively. We conclude that protection against degradation is central to
      enhancing overall release of intact CLA from ASD formulations; the formulations
      studied herein have great promise for simultaneous CLA solubility enhancement and
      protection from loss to chemical degradation, thereby reducing dose requirements
      and potentially decreasing colonic exposure to CLA (reduced colonic exposure is
      expected to minimize killing of beneficial colonic bacteria by CLA). 

PMID- 24116902
TI  - "Keep dignity intact": exploring desires for quality long-term care among midlife
      women.
AB  - The purpose of this qualitative study was to provide in-depth descriptions of
      preferences for receipt of long-term care among a small sample of information
      rich cases. The participants in this study, women in late midlife caring for a
      parent or parent-in-law, expressed where they would prefer to receive care, who
      they would want to provide care, and personal traits that would be important in a
      caregiver. A major theme centered personal characteristics these women would want
      in a caregiver, traits such as empathy, sensitivity, and knowledgeable about
      elder care. Implications for social work practice are discussed. 

PMID- 24116901
TI  - Impact of alemtuzumab treatment on the survival and function of human regulatory
      T cells in vitro.
AB  - Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein
      present at high levels on the surface of B and T lymphocytes. In clinical trials,
      alemtuzumab has shown a clinical benefit superior to that of interferon-beta in
      relapsing-remitting multiple sclerosis patients. Treatment with alemtuzumab leads
      to the depletion of circulating lymphocytes followed by a repopulation process
      characterized by alterations in the number, proportions and properties of
      lymphocyte subsets. Of particular interest, an increase in the percentage of T
      cells with a regulatory phenotype (Treg cells) has been observed in multiple
      sclerosis patients after alemtuzumab. Since Treg cells play an important role in
      the control of autoimmune responses, the effect of alemtuzumab on Treg cells was
      further studied in vitro. Alemtuzumab effectively mediated complement-dependent
      cytolysis of human T lymphocytes and the remaining population was enriched in T
      cells with a regulatory phenotype. The alemtuzumab-exposed T cells displayed
      functional regulatory characteristics including anergy to stimulation with
      allogeneic dendritic cells and ability to suppress the allogeneic response of
      autologous T cells. Consistent with the observed increase in Treg cell frequency,
      the CD25(hi) T-cell population was necessary for the suppressive activity of
      alemtuzumab-exposed T cells. The mechanism of this suppression was found to be
      dependent on both cell-cell contact and interleukin-2 consumption. These findings
      suggest that an alemtuzumab-mediated increase in the proportion of Treg cells may
      play a role in promoting the long-term efficacy of alemtuzumab in patients with
      multiple sclerosis. 

PMID- 24116903
TI  - Mechanical approaches to oncological drug delivery.

PMID- 24116904
TI  - Nanoparticulate drugs for the manipulation of angiogenesis.

PMID- 24116905
TI  - New insights for IL-6 targeted therapy as an adjuvant treatment for non-small
      cell lung cancer.

PMID- 24116908
TI  - Ask the experts: transdermal drug delivery.
AB  - Transdermal drug delivery, an arena currently worth several billions of US
      dollars, is a highly favored route of drug administration due to its convenience
      for patients and medical professionals alike. However, given the high costs in
      bringing new technologies to the market, as well as the technical issues of
      delivering drugs past the stratum corneum, the transdermal field needs to
      overcome a number of obstacles before it can realize its true potential. James
      Potticary, Assistant Commissioning Editor, spoke with three experts, discussing
      the challenges faced within the transdermal community, their motivations for
      becoming involved in the field and their visions for the future of transdermal
      drug delivery. 

PMID- 24116909
TI  - Developing siRNA therapies to address osteoporosis.
AB  - Osteoporosis is a skeletal system pathology characterized by low bone mineral
      density and tissue structural deterioration. This malady is associated with high
      fracture risk that severely compromises quality of life. Osteoporosis incidence
      is becoming more significant with increasing lifespan worldwide. However, current
      approaches for treating osteoporosis cannot and do not treat the disease in the
      most ideal manner for diverse reasons. Substantial research has sought both the
      discovery of new targets and new therapies. In this review, emerging possible
      RNAi-mediated therapeutic opportunities for osteoporosis are identified and
      associated challenges discussed. Targeted delivery strategies capable of more
      reliable and efficient delivery to skeletal tissue are described, as well as
      possibilities to treat bone-forming cells with siRNA to produce cell-based
      therapy. 

PMID- 24116910
TI  - Development of plumbagin-loaded phospholipid-Tween(r) 80 mixed micelles:
      formulation, optimization, effect on breast cancer cells and human blood/serum
      compatibility testing.
AB  - BACKGROUND: Phospholipid and Tween((r)) 80 mixed micelles were investigated as
      injectable nanocarriers for the natural anticancer compound, plumbagin (PBG),
      with the aim to improve anticancer efficiency. PBG-loaded mixed micelles were
      fabricated by self-assembly; composition being optimized using 3(2) factorial
      design. RESULTS & DISCUSSION: Optimized mixed micelles were spherical and 46 nm
      in size. Zeta potential, drug loading and encapsulation efficiency were 5.04 mV,
      91.21 and 98.38% respectively. Micelles demonstrated sustained release of PBG.
      Micelles caused a 2.1-fold enhancement in vitro antitumor activity of PBG towards
      MCF-7 cells. Micelles proved safe for intravenous injection as PBG was stable at
      high pH; micelle size and encapsulation efficiency were retained upon dilution.
      CONCLUSION: Developed mixed micelles proved potential nanocarriers for PBG in
      cancer chemotherapy.

PMID- 24116911
TI  - Availability of polymeric nanoparticles for specific enhanced and targeted drug
      delivery.
AB  - Over the past 20-30 years there has been quite a number of studies interested in
      polymeric nanoparticle (PNP) systems as a pharmaceutical approach for poorly
      soluble drugs, peptide drugs, gene and antibodies. Now, the products based on the
      PNP technologies are used in the fields of medical science, pharmaceutical
      science, tissue engineering and clothing, food and housing. This review focuses
      attention on PNPs for specific enhanced and targeted drug delivery of therapeutic
      drugs including peptide drugs as well as drug delivery applications of such
      systems. Outcomes from recent studies on polymers, how to make PNPs,
      pharmacokinetics and pharmacodynamics of PNPs, and the release profiles from PNPs
      and related systems are also described, including their pharmacokinetics and
      pharmacodynamics, if available. In addition, the latest PNP trends and will be
      described. 

PMID- 24116913
TI  - Hydrogels for controlled pulmonary delivery.
AB  - A significant number of research articles have focused on pulmonary delivery as
      an alternative administration route owing to no first-pass metabolism, low
      protease activity, thin epithelium barrier and large surface area in the lung
      system. Controlled release in the pulmonary delivery system further reduces
      loading dose, frequency of dosing and systemic side effects, and also increases
      duration of action and patient compliance. Compared with other microparticles
      used in controlled-release pulmonary administration, hydrogels (3D polymeric
      matrix networks) have recently been investigated due to their swelling and
      mucoadhesive properties that could help bypass pulmonary delivery barriers. This
      review introduces controlled-release drug delivery to the lung, followed by a
      summary of currently available approaches for controlled-release pulmonary drug
      delivery. Lastly, the origin, advantages, detailed applications and concerns of
      hydrogels in pulmonary delivery are discussed. 

PMID- 24116912
TI  - Telodendrimer-based nanocarriers for the treatment of ovarian cancer.
AB  - PEG-dendritic block copolymer (telodendrimer) is a unique class of polymers with
      well-defined structures and tunable aggregation properties, which have been
      recently developed as novel micelle-based nanocarriers. This new class of
      nanocarrier is highly versatile, robust, multifunctional and has many unique
      properties for drug delivery that are superior to most other nanocarriers
      reported in the literature. Reversible crosslinking of micelles is able to
      minimize the premature drug release during circulation. These crosslinks can be
      reversed with endogenous and/or exogenous stimuli. To further facilitate the
      precise delivery of nanoparticle drugs to cancer cells, the nanoparticles surface
      can be decorated with ovarian cancer targeting ligands. This review is focused on
      the various strategies used for the design, preparation, pharmacokinetic,
      biodistribution and preclinical therapeutic applications of telodendrimer-based
      nanocarriers for drug delivery in the treatment of ovarian cancer. Lastly, future
      perspectives for the development of ovarian cancer-targeting telodendrimer
      nanotherapeutics are also explored. 

PMID- 24116914
TI  - Cancer immunotherapy: accomplishments to date and future promise.
AB  - Cancer remains a devastating disease as existing therapies are too often
      ineffective and toxicities remain unacceptably high. Immunotherapies for cancer
      offer the promise of the specificity and memory of the immune system against
      malignant cells to achieve durable cure with minimal toxicity. Beginning with the
      success of bone marrow transplantation for blood-borne cancers, and the more
      recent development of monoclonal antibody therapeutics for a variety of tumors,
      immunotherapies are already among the most successful class of treatments for
      cancer. Greater understanding of immunoregulatory mechanisms and improved
      techniques for immune cell manipulation and engineering have led to new
      immunomodulatory approaches and cell-based therapies for cancer that have
      generated great excitement within the biomedical community. As these technologies
      continue to improve, and as new approaches for harnessing the power and
      specificity of the immune system are developed, immunotherapies will play an
      increasingly important role in the treatment of cancer. Here, we review the
      history of immunotherapies for cancer and discuss existing and emerging
      immunotherapy technologies that hope to translate the promise of immunotherapy
      into clinical reality. 

PMID- 24116915
TI  - Novel therapy based on camelid nanobodies.
AB  - Nanobodies (Nbs) are small antibody fragments derived from camelid heavy chain
      antibodies through recombinant gene technology. Their exceptional physicochemical
      properties, possibility of humanization and unique antigen recognition properties
      make them excellent candidates for targeted delivery of biologically active
      components. Several different therapeutic approaches based on the novel camelid
      Nbs have been developed to treat a wide range of diseases ranging from immune,
      bone, blood and neurological disorders; infectious diseases and cancer. This
      review provides a comprehensive overview of the current state of the use of
      camelid-derived Nbs as novel therapeutic agents against multiple diseases. 

PMID- 24116917
TI  - Dominant PRPF31 mutations are hypostatic to a recessive CNOT3 polymorphism in
      retinitis pigmentosa: a novel phenomenon of "linked trans-acting epistasis".
AB  - Mutations in PRPF31 are responsible for autosomal dominant retinitis pigmentosa
      (adRP, RP11 form) and affected families show nonpenetrance. Differential
      expression of the wildtype PRPF31 allele is responsible for this phenomenon:
      coinheritance of a mutation and a higher expressing wildtype allele provide
      protection against development of disease. It has been suggested that a major
      modulating factor lies in close proximity to the wildtype PRPF31 gene on
      Chromosome 19, implying that a cis-acting factor directly alters PRPF31
      expression. Variable expression of CNOT3 is one determinant of PRPF31 expression.
      This study explored the relationship between CNOT3 (a trans-acting factor) and
      its paradoxical cis-acting nature in relation to RP11. Linkage analysis on
      Chromosome 19 was performed in mutation-carrying families, and the inheritance of
      the wildtype PRPF31 allele in symptomatic-asymptomatic sibships was assessed
      confirming that differential inheritance of wildtype chromosome 19q13 determines
      the clinical phenotype (P < 2.6 * 10(-7) ). A theoretical model was constructed
      that explains the apparent conflict between the linkage data and the recent
      demonstration that a trans-acting factor (CNOT3) is a major nonpenetrance factor:
      we propose that this apparently cis-acting effect arises due to the intimate
      linkage of CNOT3 and PRPF31 on Chromosome 19q13-a novel mechanism that we have
      termed "linked trans-acting epistasis." 

PMID- 24116919
TI  - Classical texts in the present tense: the looking diagnosis of a Donguibogam
      school in South Korea.
AB  - OBJECTIVES: This paper examines the meanings of classical texts in contemporary
      East Asian medicine. METHODS: This study conducted anthropological fieldwork of
      the Hyungsang Medical Society, the major practitioner association in South Korea,
      which follows the teachings of Donguibogam (Bogam), one of the most influential
      texts in contemporary Korean medicine. Field data were collected by long-term
      observation of clinical practices at member clinics, in-depth interviews with
      practitioners, and participation in activities of the medical society. RESULTS:
      The Hyungsang Medical Society follows Bogam's emphases-such as the fundamental
      constituents of human beings and the constitutional differences among persons-and
      actualizes the teachings in Hyungsang medical theory. Hyungsang medicine proposes
      several person types, based on bodily appearances, that inform a person's inner
      status. These types illustrate emerging diagnostic methods derived from Bogam.
      The Jung (essence), Ki (energy), Shin (spirit), and Hyeol (blood) types are
      developed with a premise that disproportionate composition of the fundamental
      constituents leads to different face shapes among the four types of persons. A
      case developed in this study demonstrates that once a patient is identified as
      one of the types, the practitioner gains an advantageous position to approach the
      patient's health issues. CONCLUSIONS: The emerging person-types of Hyungsang
      medicine illustrate how a new medical practice is taking place in East Asian
      medicine today through contemporary actors' interpretation and actualization of
      classical texts, suggesting that classical texts play, and have the potential to
      play, a continuing role in East Asian medicine.

PMID- 24116918
TI  - The role of parent psychopathology in the development of preschool children with
      behavior problems.
AB  - The present study examined associations between early parental self-reported
      psychopathology symptoms and the later behavioral, emotional, and social
      functioning of preschool children with behavior problems. Mothers and fathers of
      preschoolers with behavior problems (N = 132; 55 girls, 77 boys) completed parent
      psychopathology questionnaires when children were 3 years old and completed
      measures of children's externalizing, internalizing, and social problems annually
      from age 3 to age 6. The sample included 61% European American, 16% Latino
      (predominantly Puerto Rican), 10% African American, and 13% multiethnic children.
      Every dimension of mothers' and fathers' psychopathology symptoms when children
      were 3 years old was associated with their own reports of children's
      externalizing and internalizing problems 3 years later. Several dimensions of
      maternal psychopathology symptoms at age 3 were associated with mother-reported
      social skills 3 years later. However, the relation between many dimensions of
      psychopathology symptoms and child outcome appears to be accounted for by co
      occurring psychopathology symptoms. Only maternal attention-deficit hyperactivity
      disorder (ADHD) and Cluster A symptoms, and paternal ADHD and depression/anxiety
      symptoms emerged as unique predictors of child functioning. These findings
      suggest that most types of mothers' and fathers' self-reported psychopathology
      symptoms may play a role in the prognosis of behavioral, social, and emotional
      outcomes of preschoolers with behavior problems, but that co-occurring symptoms
      need to be considered. 

PMID- 24116920
TI  - When do self-discrepancies predict negative emotions? Exploring formal
      operational thought and abstract reasoning skills as moderators.
AB  - Individual differences in higher-order cognitive abilities may be an important
      piece to understanding how and when self-discrepancies lead to negative emotions.
      In the current study, three measures of reasoning abilities were considered as
      potential moderators of the relationship between self-discrepancies and
      depression and anxiety symptoms. Participants (N = 162) completed measures
      assessing self-discrepancies, depression and anxiety symptoms, and were
      administered measures examining formal operational thought, and verbal and non
      verbal abstract reasoning skills. Both formal operational thought and verbal
      abstract reasoning were significant moderators of the relationship between
      actual:ideal discrepancies and depressive symptoms. Discrepancies predicted
      depressive symptoms for individuals with higher levels of formal operational
      thought and verbal abstract reasoning skills, but not for those with lower
      levels. The discussion focuses on the need to consider advanced reasoning skills
      when examining self-discrepancies. 

PMID- 24116921
TI  - Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type
      2.
AB  - The objective of this study was to investigate ethnic differences in the
      glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene in patients with
      primary hyperoxaluria type 2 (PH2). GRHPR was genotyped in Japanese patients with
      PH2 and all GRHPR mutations described to date were reviewed in terms of
      geographic and ethnic association. We identified a novel mutation, a two
      nucleotide deletion (c.248_249delTG) in exon 3 creating a premature 'stop' at
      codon 91. Also, we found that the c.864_865delTG mutation was associated with the
      rs35891798 single-nucleotide polymorphism. The allelic frequencies of the
      c.103delG, c.494G>A, c.403_404+2 delAAGT, and c.864_865delTG mutations in PH2
      patients were 37.8%, 15.6%, 10.0%, and 10.0%, respectively. All patients with the
      c.103delG mutation were Caucasian. Patients with the c.494G>A mutation and 78%
      (7/9) of those with the c.403_404+2 delAAGT mutation were from the Indian
      subcontinent, whereas those with the c.864_865delTG mutation were Chinese or
      Japanese. Molecular analysis of GRHPR of four Japanese PH2 patients identified a
      novel mutation (c.248_249delTG in exon 3). Caucasians with PH2 should be screened
      for the c.103delG mutation; patients from the Indian subcontinent for c.494G>A;
      and patients of East Asian origin (particularly) for c.864_865delTG. The
      prevalence of the latter mutation in PH2 patients from East Asia was 75.0%. 

PMID- 24116922
TI  - Effects of an intervention addressing information, motivation, and behavioral
      skills on HIV care adherence in a southern clinic cohort.
AB  - Multiple studies have shown that subtherapeutic appointment adherence and
      medication adherence are associated with worse clinical outcomes for people
      living with HIV disease. Thus, poor appointment and medication adherence diminish
      individual and community HIV control and transmission. Yet not enough is known
      about interventions that can improve retention in HIV care. The purpose of this
      study was to test an intervention to improve retention and/or medication
      adherence in a public clinic in the Deep South. One hundred participants with
      retention or medication adherence difficulties were randomized to either a six
      month intervention or usual care, and followed longitudinally for one year. The
      intervention was multidimensional, based on the Information-Motivation-Behavioral
      Skills (IMB) model. The intervention addressed information about HIV and the
      importance of retention/adherence, motivation to be retained and/or adhere to
      medications, and the behavioral skills needed to manage and maintain these
      healthy behaviors in a combination of face-to-face and telephone sessions. The
      proportion of those with at least one visit in each four-month block (third) of
      the year increased in those with minimal exposure to the intervention (three out
      of eight intervention contacts) as compared to those with less intervention
      exposure (p = 0.098). Those with at least this minimal exposure averaged a
      significantly higher number of thirds that included a clinic visit as compared to
      those with less intervention exposure (p = 0.013). The intervention did not
      demonstrate a significant effect on medication adherence, though this is
      contradictory to a previous study testing a version of this intervention designed
      to address only medication adherence. Further study to increase uptake of the
      intervention is needed to increase its efficacy.

PMID- 24116923
TI  - "We've been here before...".

PMID- 24116924
TI  - Functional consequences of the open distal pocket of dehaloperoxidase-hemoglobin
      observed by time-resolved X-ray crystallography.
AB  - Using time-resolved X-ray crystallography, we contrast a bifunctional
      dehaloperoxidase-hemoglobin (DHP) with previously studied examples of myoglobin
      and hemoglobin to understand the functional role of the distal pocket of globins.
      One key functional difference between DHP and other globins is the requirement
      that H2O2 enter the distal pocket of oxyferrous DHP to displace O2 from the heme
      Fe atom and thereby activate the heme for the peroxidase function. The open
      architecture of DHP permits more than one molecule to simultaneously enter the
      distal pocket of the protein above the heme to facilitate the unique peroxidase
      cycle starting from the oxyferrous state. The time-resolved X-ray data show that
      the distal pocket of DHP lacks a protein valve found in the two other globins
      that have been studied previously. The photolyzed CO ligand trajectory in DHP
      does not have a docking site; rather, the CO moves immediately to the Xe-binding
      site. From there, CO can escape but can also recombine an order of magnitude more
      rapidly than in other globins. The contrast with DHP dynamics and function more
      precisely defines the functional role of the multiple conformational states of
      myoglobin. Taken together with the high reduction potential of DHP, the open
      distal site helps to explain how a globin can also function as a peroxidase. 

PMID- 24116925
TI  - A person-centred analysis of teacher-child relationships in early childhood.
AB  - BACKGROUND: Previously, the nature of teacher-child relationships (TCRs) has been
      explored through dimensions of close, conflicted, and dependent. However, this
      variable-centred approach is limited, as many relationships can be characterized
      by more than one characteristic or trait. A person-centred approach would allow
      for a greater understanding of the types of relationships that are formed and
      improved interpretation of the students' socio-emotional outcomes associated with
      that relationship. AIMS: The primary goal of this study was to examine the socio
      emotional functioning of young children who formed distinct types of TCRs.
      SAMPLE: Participants were n = 202 kindergarten children (98 girls, 104 boys, Mage
      = 64.12 months, SD = 4.86). METHOD: Multi-source assessment was employed with
      data collected from parent ratings, teacher reports, child interviews, and
      naturalistic observations in the classroom. Using quartile cut-offs, we
      identified children who formed conflicted, dependent, and 'combined' (conflicted
      and dependent) TCRs. RESULTS: Results indicated distinct patterns of socio
      emotional functioning for each TCR group. For example, whereas children in
      conflicted TCRs evidenced greater externalizing difficulties, children with
      dependent TCRs had greater internalizing difficulties. Children who evidenced
      high levels of both conflicted and dependent TCRs displayed the most pervasive
      socio-emotional difficulties. CONCLUSIONS: Children who form TCRs characterized
      by high levels of both conflict and dependency displayed the most pervasive
      adjustment difficulties. Further investigation is needed to improve our
      understanding of this group and to assess the plausibility of early intervention
      strategies.

PMID- 24116926
TI  - Ophthalmic abnormalities in children with developmental coordination disorder.
AB  - AIM: To explore associations between developmental coordination disorder (DCD)
      and ophthalmic abnormalities in children aged 7 to 8 years. METHOD: Cross
      sectional analysis of data from the Avon Longitudinal Study of Parents and
      Children (ALSPAC), a UK birth cohort, was performed. DCD was defined according to
      DSM-IV criteria. Children with neurological difficulties or IQ less than 70 were
      excluded. Ophthalmic abnormalities including visual acuity, refraction, and
      binocular function were assessed using standard tests. Children who achieved less
      than the 5th centile in the ALSPAC coordination test and either failed the
      National Curriculum handwriting test, or achieved less than the 10th centile in
      the Activities of Daily Living scale (ADL) were defined as having severe DCD,
      while those who scored between the 5th and 15th centiles in the coordination test
      and either failed the handwriting test, or achieved less than the 15th centile in
      the ADL were defined as having moderate DCD. RESULTS: Complete data were
      available for 7154 children. One hundred and twenty children (1.8%) met the
      criteria for severe DCD. A further 215 children had moderate DCD. Children with
      severe DCD were more likely to have the following: abnormal sensory fusion at
      near (odds ratio [95% confidence interval]) (1.98 [1.13-3.48]) and distance (2.59
      [1.16-5.79]) and motor fusion (1.74 [1.07-2.84]); reduced stereoacuity (2.75
      [1.78-4.23]); hypermetropia (2.29 [1.1-4.57]) and anisometropia (2.27 [1.13
      4.60]). The majority of children found to have both DCD and a refractive error,
      had been previously prescribed glasses and wore them for the assessments (71%).
      INTERPRETATION: Children with severe DCD had abnormalities in binocular vision,
      refractive error, and ocular alignment. We recommend that children with DCD be
      assessed for ocular abnormalities as early intervention may improve long-term
      visual outcome. The impact of untreated ocular abnormalities such as refractive
      error on the accuracy of the diagnosis of DCD is difficult to ascertain and
      further work would be of benefit.

PMID- 24116927
TI  - Follicular bronchiolitis as phenotype associated with CD25 deficiency.
AB  - Regulatory T cells [Tregs ; CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+) )]
      are subsets of T cells involved in the maintenance of peripheral self-tolerance
      by actively suppressing the activation and expansion of autoreactive T cells.
      Signalling through the interleukin-2 receptor (IL-2R) contributes to T cell
      tolerance by controlling three important aspects of regulatory T cell (Treg )
      biology. CD25 is the alpha-chain of the IL-2R that, in concert with the beta
      chain and gamma-chain, constitutes the complete IL-2R. CD25 contributes only to
      IL-2 binding affinity but not to the recruitment of signalling molecules.
      However, its importance in the development of a normal immune response is
      emphasized by the finding that a truncation mutant of CD25 results in an
      immunodeficiency in humans characterized by an increased susceptibility to viral,
      bacterial and fungal infections. In 1997, Sharfe et al. described an infant with
      severe bacterial, viral and fungal infections. Counts of autologous T lymphocytes
      were moderately low, T cells displayed a weak proliferative response to mitogens
      in vitro and the patient displayed no rejection of an allogeneic skin graft.
      However, unlike children with severe combined immunodeficiency (SCID), besides
      not having circulating T cells, the patient also developed peripheral lymphocytic
      proliferation and autoimmune primary biliary cirrhosis. We present the first
      female Argentine patient with mutation in CD25 associated with chronic and severe
      inflammatory lung disease (follicular bronchiolitis with lymphocyte hyperplasia),
      eczema and infections. She has no expression of CD25 on CD4(+) T cells and an
      extremely low amount of Tregs . The molecular study confirmed homozygous missense
      mutation in the alpha subunit of the IL-2 receptor (CD25alphaR) (c. 122 a > c; p.
      Y41S). 

PMID- 24116928
TI  - Changes in the sublingual microcirculation during major abdominal surgery and
      post-operative morbidity.
AB  - BACKGROUND: Little is known about perioperative microcirculatory changes during
      major abdominal surgery, and the main objectives of this study were to evaluate
      perioperative microcirculatory alterations in this setting, and if changes in
      microcirculatory parameters are associated with post-operative morbidity and/or
      with changes in parameters reflecting oxygen delivery. METHODS: Patients
      scheduled for major abdominal surgery with an estimated Portsmouth Physiological
      and Operative Severity Score for the enUmeration of Mortality and morbidity (P
      POSSUM) score of > 30 and operation time > 3 h were eligible for inclusion.
      Perioperative microcirculatory alterations were evaluated in the sublingual
      mucosa using Sidestream Dark Field (SDF) imaging. Perfused vessel density (PVD),
      vessel perfusion [microvascular flow index (MFI)], and flow heterogeneity
      [heterogeneity index (HI)] were analysed. Central venous oxygen saturation
      (ScvO2) and lactate were measured simultaneously. During a 30-day follow-up
      period, post-operative complications were registered according to predefined
      criteria. RESULTS: Forty-two patients with a median P-POSSUM of 33 were included
      in the study. MFI was higher during anaesthesia than pre- and post-anaesthesia.
      PVD and HI did not change during the observation period. Lactate and ScvO2
      increased during surgery. Perioperative lactate and ScvO2 values were not
      correlated with microcirculatory parameters. Complications occurred in 16
      patients. No differences in microcirculatory parameters were detected between
      patients with and without complications. CONCLUSIONS: Perioperative changes in
      the sublingual microcirculatory parameters measured with the SDF-imaging
      technique appear to be minor, and no association with outcome after major
      abdominal surgery could be demonstrated. Changes in ScvO2 and serum lactate do
      not reflect sublingual microcirculatory alterations in this setting.

PMID- 24116929
TI  - Single nucleotide polymorphism array analysis of bone marrow failure patients
      reveals characteristic patterns of genetic changes.
AB  - The bone marrow failure syndromes (BMFS) are a heterogeneous group of rare blood
      disorders characterized by inadequate haematopoiesis, clonal evolution, and
      increased risk of leukaemia. Single nucleotide polymorphism arrays (SNP-A) have
      been proposed as a tool for surveillance of clonal evolution in BMFS. To better
      understand the natural history of BMFS and to assess the clinical utility of SNP
      A in these disorders, we analysed 124 SNP-A from a comprehensively characterized
      cohort of 91 patients at our BMFS centre. SNP-A were correlated with medical
      histories, haematopathology, cytogenetic and molecular data. To assess clonal
      evolution, longitudinal analysis of SNP-A was performed in 25 patients. We found
      that acquired copy number-neutral loss of heterozygosity (CN-LOH) was
      significantly more frequent in acquired aplastic anaemia (aAA) than in other BMFS
      (odds ratio 12.2, P < 0.01). Homozygosity by descent was most common in
      congenital BMFS, frequently unmasking autosomal recessive mutations. Copy number
      variants (CNVs) were frequently polymorphic, and we identified CNVs enriched in
      neutropenia and aAA. Our results suggest that acquired CN-LOH is a general
      phenomenon in aAA that is probably mechanistically and prognostically distinct
      from typical CN-LOH of myeloid malignancies. Our analysis of clinical utility of
      SNP-A shows the highest yield of detecting new clonal haematopoiesis at diagnosis
      and at relapse. 

PMID- 24116931
TI  - Manipulating and dispensing micro/nanoliter droplets by superhydrophobic needle
      nozzles.
AB  - There is rapidly increasing research interest focused on manipulating and
      dispensing tiny droplets in nanotechnology and biotechnology. A
      micro/nanostructured superhydrophobic nozzle surface is one promising candidate
      for the realization of tiny droplet manipulating applications. Here, we explore
      the feasibility of using superhydrophobicity for guided dispensing of tiny water
      droplets. A facile dip-coating method is developed to prepare superhydrophobic
      needle nozzles (SNNs) based on commercial needle nozzles with reduced inner
      diameter. The SNNs can manipulate tiny droplets of different volumes by only
      changing the inner diameter of the nozzle, rather than reducing the nozzle size
      as a whole. Different from the previous electric-field-directed process or
      pyroelectrodynamic-driven technique, quasi-stable water drops down to the
      picoliter scale can be produced by SNNs without employing any extra driving
      mechanisms. Due to their intrinsic superhydrophobic nature, the SNNs also possess
      the properties of reducing sample liquid retention, improving sample volume
      transfer accuracy, and saving expensive reagents. In addition, this kind of dip
      coating method can also be applied to micropipet tips, inkjet or bio-printer
      heads, etc. As the issues of reducing drop size and increasing drop volume
      accuracy are quite important in the laboratory and industry, this facile but
      effective superhydrophobic nozzle-coating method for manipulating tiny droplets
      could be of great help to make breakthroughs in next-generation liquid transport
      and biometric and inkjet printing devices. 

PMID- 24116932
TI  - DNA-directed gold nanodimers with tailored ensemble surface-enhanced Raman
      scattering properties.
AB  - Gold nanodimers (GNDs) are assembled with high uniformity as ideal surface
      enhanced Raman scattering (SERS) substrates through DNA-directed self-assembly of
      gold nanoparticles. The interparticle distance within GNDs is precisely tailored
      on the order of a few nanometers with changing the molecule length of DNA bridge.
      The ensemble SERS activity of monodispersed GNDs is then rationally engineered by
      modifying the structural parameters of GNDs including the particle size and
      interparticle distance. Theoretical studies on the level of single GND evidence
      the particle size- and interparticle-distance-dependent SERS effects, consistent
      with the ensemble averaged measurements. 

PMID- 24116930
TI  - The structural role of receptor tyrosine sulfation in chemokine recognition.
AB  - Tyrosine sulfation is a post-translational modification of secreted and
      transmembrane proteins, including many GPCRs such as chemokine receptors. Most
      chemokine receptors contain several potentially sulfated tyrosine residues in
      their extracellular N-terminal regions, the initial binding site for chemokine
      ligands. Sulfation of these receptors increases chemokine binding affinity and
      potency. Although receptor sulfation is heterogeneous, insights into the
      molecular basis of sulfotyrosine (sTyr) recognition have been obtained using
      purified, homogeneous sulfopeptides corresponding to the N-termini of chemokine
      receptors. Receptor sTyr residues bind to a shallow cleft defined by the N-loop
      and beta3-strand elements of cognate chemokines. Tyrosine sulfation enhances the
      affinity of receptor peptides for cognate chemokines in a manner dependent on the
      position of sulfation. Moreover, tyrosine sulfation can alter the selectivity of
      receptor peptides among several cognate chemokines for the same receptor.
      Finally, binding to receptor sulfopeptides can modulate the oligomerization state
      of chemokines, thereby influencing the ability of a chemokine to activate its
      receptor. These results increase the motivation to investigate the structural
      basis by which tyrosine sulfation modulates chemokine receptor activity and the
      biological consequences of this functional modulation.

PMID- 24116933
TI  - Conservative management of abnormally invasive placenta after vaginal delivery.

PMID- 24116934
TI  - Photo(chemo)therapy in the management of atopic dermatitis: an updated systematic
      review with implications for practice and research.
AB  - BACKGROUND: Photo(chemo)therapy is a common treatment modality in patients with
      atopic dermatitis (AD), but evidence on its effectiveness has not been recently
      systematically reviewed. OBJECTIVES: To evaluate the effect of treatment with
      photo(chemo)therapy in patients with AD and to make treatment recommendations on
      basis of the evidence. METHODS: We performed an electronic literature search in
      MEDLINE (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials
      (CENTRAL), Global Resource of EczemA Trials (GREAT) and prospective trial
      registers, complemented with a search of PubMed to find recent studies not yet
      available in OVID MEDLINE. All randomized controlled trials (RCTs) on
      phototherapy for the treatment of AD were considered for data extraction.
      RESULTS: Nineteen studies were included (905 participants). The identified RCTs
      were generally clinically and qualitatively heterogeneous. Therefore a formal
      meta-analysis was not feasible. Conclusions must be drawn carefully because of
      small sample sizes, varying study quality and sometimes the absence of direct
      comparisons, but on the basis of the included evidence, ultraviolet (UV) A1 and
      narrowband (NB)-UVB appeared the most effective treatment modalities for the
      reduction of clinical signs and symptoms. No difference between high-dose UVA1
      and medium-dose UVA1 was seen. UVAB was shown to be more effective than UVA and
      broadband-UVB for the improvement of clinical symptoms, but not compared with
      UVA1. Other effective treatment options include full-spectrum light, psoralen
      plus UVA and balneophototherapy. No serious side-effects were reported.
      CONCLUSIONS: Phototherapy can be a valid therapeutic option for patients with AD.
      Based on the results of this review, preference is given to UVA1 and NB-UVB.
      Further well-designed, adequately powered RCTs are required.

PMID- 24116935
TI  - NMR investigations of dinuclear, single-anion bridged copper(II) metallacycles:
      structure and antiferromagnetic behavior in solution.
AB  - The nuclear magnetic resonance (NMR) spectra of single-anion bridged, dinuclear
      copper(II) metallacycles [Cu2(MU-X)(MU-L)2](A)3 (L(m) = m-bis[bis(1
      pyrazolyl)methyl]benzene: X = F(-), A = BF4(-); X = Cl(-), OH(-), A = ClO4(-);
      L(m)* = m-bis[bis(3,5-dimethyl-1-pyrazolyl)methyl]benzene: X = CN(-), F(-), Cl(
      ), OH(-), Br(-), A = ClO4(-)) have relatively sharp (1)H and (13)C NMR resonances
      with small hyperfine shifts due to the strong antiferromagnetic superexchange
      interactions between the two S = 1/2 metal centers. The complete assignments of
      these spectra, except X = CN(-), have been made through a series of NMR
      experiments: (1)H-(1)H COSY, (1)H-(13)C HSQC, (1)H-(13)C HMBC, T1 measurements
      and variable-temperature (1)H NMR. The T1 measurements accurately determine the
      Cu...H distances in these molecules. In solution, the temperature dependence of
      the chemical shifts correlate with the population of the paramagnetic triplet (S
      = 1) and diamagnetic singlet (S = 0) states. This correlation allows the
      determination of antiferromagnetic exchange coupling constants, -J (H = -JS1S2),
      in solution for the L(m) compounds 338(F(-)), 460(Cl(-)), 542(OH(-)), for the
      L(m)* compounds 128(CN(-)), 329(F(-)), 717(Cl(-)), 823(OH(-)), and 944(Br(-)) cm(
      1), respectively. These values are of similar magnitudes to those previously
      measured in the solid state (-Jsolid = 365, 536, 555, 160, 340, 720, 808, and 945
      cm(-1), respectively). This method of using NMR to determine -J values in
      solution is an accurate and convenient method for complexes with strong
      antiferromagnetic superexchange interactions. In addition, the similarity between
      the solution and solid-state -J values of these complexes confirms the
      information gained from the T1 measurements: the structures are similar in the
      two states.

PMID- 24116936
TI  - Vertical perithalamic hemispherotomy: a single-center experience in 40 pediatric
      patients with epilepsy.
AB  - PURPOSE: The current concept for hemispherotomy includes various lateral
      techniques and the vertical perithalamic hemispherotomy introduced by Delalande
      in 1992. We have chosen the vertical approach because of advantages that possibly
      influence outcome: the possibility to completely disconnect the hemisphere at the
      level of the thalamus obviating both the need to resect the insula and the need
      to open and dissect the subarachnoid space of the Sylvian fissure. METHODS: We
      retrospectively analyzed prospectively collected data of all patients who
      underwent vertical hemispherotomy at the Vienna pediatric epilepsy center.
      Seizure outcome was classified according to the International League Against
      Epilepsy (ILAE) proposal 2001. KEY FINDINGS: Follow-up data of 40 patients (22
      male/18 female; median age 5.5 years; range 4.4 months to 20.1 years) were
      analyzed. Hemispherotomy was left in 26 and right in 14 patients. The underlying
      pathology was ischemic vascular in 19, malformation of cortical development (MCD)
      in 11, and other pathology in 10. No serious intraoperative complications were
      encountered. Only two infants (5.0%) needed blood replacement. There was one
      death on the fourth day after surgery caused by intractable hyponatremic brain
      edema. Three patients developed cerebrospinal fluid (CSF) disturbances, but only
      one needed a permanent ventriculoperitoneal (VP) shunt (2.5%). For outcome
      analysis we included 37 of 40 children with at least 12 months of follow-up.
      Thirty-four (91.9%) of 37 children were seizure-free (class 1a) after a median
      follow-up time of 3.7 years (range 12 month to 14.8 years). SIGNIFICANCE: We
      confirm the efficacy and safety of vertical parasagittal hemispherotomy as
      described by Delalande in a consecutive series of patients treated at our center
      since 1998. In addition, complete disconnection of the hemisphere in patients
      with MCD and/or patients with significant involvement of the insula was possible
      without the complications usually reported with other techniques.

PMID- 24116937
TI  - Manipulation of olfactory tight junctions using papaverine to enhance intranasal
      delivery of gemcitabine to the brain.
AB  - CONTEXT: Delivery of drugs from the nasal cavity to the brain is becoming more
      widely accepted, due to the non-invasive nature of this route and the ability to
      circumvent the blood brain barrier (BBB). OBJECTIVE: Because of similarities in
      the proteins comprising the olfactory epithelial tight junction (TJ) proteins and
      those of the BBB, we sought to determine whether papaverine (PV), which is known
      to reversibly enhance BBB permeability, could increase the delivery of
      intranasally administered gemcitabine to the central nervous system in rats.
      Experimental methods: Included intranasal administration of gemcitabine,
      fluorescein isothiocyanate-dextran beads and PV, histopathology, immunostaining,
      RT-PCR, western blot analysis, immunofluorescence localization,
      spectrofluorometric analysis, in vivo brain microdialysis, HPLC analysis and in
      vitro gemcitabine recovery. RESULTS AND DISCUSSION: PV transiently decreased the
      levels and altered immunolocalization of the TJ protein phosphorylated-occludin
      in the olfactory epithelium, while causing an approximately four-fold increase in
      gemcitabine concentration reaching the brain. The enhanced delivery was not
      accompanied by nasal epithelial damage or toxicity to distant organs.
      CONCLUSIONS: The ability to transiently and safely increase drug delivery from
      the nose to the brain represents a non-invasive way to improve treatment of
      patients with brain disorders.

PMID- 24116938
TI  - Synesthetic experiences enhance unconscious learning.
AB  - Synesthesia  is characterized  by consistent extra perceptual experiences in
      response to normal sensory input. Recent studies provide evidence for a specific
      profile of enhanced memory performance in synesthesia, but focus exclusively on
      explicit memory paradigms for which the learned content is consciously
      accessible. In this study, for the first time, we demonstrate with an implicit
      memory paradigm that synesthetic experiences also enhance memory performance
      relating to unconscious knowledge. 

PMID- 24116939
TI  - Development of a high-throughput screening-compatible cell-based functional assay
      to identify small molecule probes of the galanin 3 receptor (GalR3).
AB  - The galanin 3 receptor (GalR3) belongs to the large G protein-coupled receptor
      (GPCR) family of proteins. GalR3 and two other closely related receptors, GalR1
      and GalR2, together with their endogenous ligand galanin, are involved in a
      variety of physiological and pathophysiological processes. GalR3 in particular
      has been strongly implicated in addiction and mood-related disorders such as
      anxiety and depression. It has been the target of many drug discovery programs
      within the pharmaceutical industry, but despite the significant resources and
      effort devoted to discovery of galanin receptor subtype selective small molecule
      modulators, there have been very few reports for the discovery of such molecules.
      GalR3 has proven difficult to enable in cell-based functional assays due to its
      apparent poor cell surface expression in recombinant systems. Here, we describe
      the generation of a modified GalR3 that facilitates its cell surface expression
      while maintaining wild-type receptor pharmacology. The modified GalR3 has been
      used to develop a high-throughput screening-compatible, cell-based, cAMP
      biosensor assay to detect selective small molecule modulators of GalR3. The
      performance of the assay has been validated by challenging it against a test
      library of small molecules with known pharmacological activities (LOPAC; Sigma
      Aldrich). This approach will enable identification of GalR3 selective modulators
      (chemical probes) that will facilitate dissection of the biological role(s) that
      GalR3 plays in normal physiological processes as well as in disease states.

PMID- 24116940
TI  - Expression and purification of recombinant human apolipoprotein A-II in Pichia
      pastoris.
AB  - Apolipoprotein A-II (ApoA-II) is the second most abundant protein constituent of
      high-density lipoprotein (HDL). The physiologic role of ApoA-II is poorly
      defined. ApoA-II may inhibit lecithin:cholesterol acyltransferase and cholesteryl
      ester-transfer protein activities, but may increase the hepatic lipase activity.
      ApoA-II may also inhibit the hepatic cholesteryl uptake from HDL probably through
      the scavenger receptor class B type I depending pathway. Interpretation of data
      from transgenic and knockout mice of genes involved in lipoprotein metabolism has
      been often complicated as clinical implications because of species difference. So
      it is important to obtain human ApoA-II for further studies about its functions.
      In our studies, Pichia pastoris expression system was first used to express a
      high-level secreted recombinant human ApoA-II (rhApoA-II). We have cloned the
      cDNA encoding human ApoA-II and achieved its high-level secreting expression with
      a yield of 65 mg/L of yeast culture and the purification process was effective
      and easy to handle. The purified rhApoA-II can be used to further study its
      biological activities.

PMID- 24116941
TI  - A critical evaluation of migraine trigger site deactivation surgery.
AB  - Migraine headache trigger site deactivation surgery is a term that encompasses 4
      different surgical procedures that are performed based on headache onset location
      for the preventative treatment of migraine headaches. Multiple studies have
      demonstrated some efficacy of these procedures, but closer evaluation of the
      methodology of these studies reveals major flaws in study design. In this
      article, the author provides an overview of the procedures and presurgical
      screening tools, as well as a critical evaluation of 2 of the major studies that
      have been published. In addition, the author provides his opinion on future study
      designs that may help to better determine the potential efficacy of these
      experimental procedures and potential headache subtypes (contact point headache,
      supraorbital neuralgia, and occipital neuralgia) that may respond to peripheral
      decompression surgery. 

PMID- 24116942
TI  - Breast cancer genetics: 20 years later.

PMID- 24116943
TI  - AAV2/8 vectors purified from culture medium with a simple and rapid protocol
      transduce murine liver, muscle, and retina efficiently.
AB  - During the production of some adeno-associated virus (AAV) serotypes, a large
      amount of vectors is found in the medium of producing cells. For their
      purification, previous protocols used tangential flow filtration (TFF) of the
      medium followed by iodixanol gradient centrifugation. Taking advantage of the
      higher purity of the medium than the cell-derived material as the source of AAV,
      we tested a simple method that combines production of large culture medium
      volumes containing AAV from cell stacks with medium clarification+TFF without
      further time-consuming and nonscalable centrifugation. To test this, we selected
      AAV2/8, which is emerging as a favored serotype for transduction of liver,
      muscle, and retina and abundantly found in the extracellular medium. We show that
      yields and in vitro infectivity of AAV2/8 vectors produced from the culture
      medium using this method are higher than those of vectors purified from the same
      cell lysate using a conventional CsCl2 gradient ultracentrifugation-based method,
      although purity appears inferior. In addition, we found that the transduction
      efficiency of AAV2/8 purified from medium was similar to that of AAV2/8 purified
      from the same cell lysate in the murine liver, muscle, and retina. Considering
      that the purification protocol from the medium we describe requires 3 hr as
      opposed to the 63 hr of a conventional two-round CsCl2-gradient
      ultracentrifugation+desalting, we conclude that TFF of the medium containing
      AAV2/8 represents a quick and scalable method to purify research-grade vectors
      for use in animal models.

PMID- 24116944
TI  - Antimony-based ligand exchange to promote crystallization in spray-deposited
      Cu2ZnSnSe4 solar cells.
AB  - A multistrategy approach to overcome the main challenges of nanoparticle-based
      solution-processed Cu2ZnSnSe4 thin film solar cells is presented. We developed an
      efficient ligand exchange strategy, using an antimony salt, to displace organic
      ligands from the surface of Cu2ZnSnS4 nanoparticles. An automated pulsed spray
      deposition system was used to deposit the nanoparticles into homogeneous and
      crack-free films with controlled thickness. After annealing the film in a Se-rich
      atmosphere, carbon-free and crystalline Cu2ZnSnSe4 absorber layers were obtained.
      Not only was crystallization promoted by the complete removal of organics, but
      also Sb itself played a critical role. The Sb-assisted crystal growth is
      associated with the formation of a Sb-based compound at the grain boundaries,
      which locally reduces the melting point, thus promoting the film diffusion
      limited crystallization. 

PMID- 24116945
TI  - Noncompliance: the pot calling the kettle black.

PMID- 24116946
TI  - Methadone rotation for cancer patients with refractory pain in a palliative care
      unit: an observational study.
AB  - BACKGROUND: Methadone has been reported to be as effective as morphine for cancer
      pain management. It is commonly used as an alternative opioid in case of
      insufficient relief. OBJECTIVE: Our aim was to assess efficacy and tolerance of
      opioid rotation to methadone for refractory cancer pain management in palliative
      care unit (PCU) inpatients. METHODS: All the patients undergoing opioid rotation
      to methadone from 2008 to 2011 in two PCUs (Lyon and Nice, France) were included.
      Pain assessments were undertaken on day 0 (D0), day 3 (D3), day 7 (D7), and day
      14 (D14) using a visual analogue scale (VAS; 0-10) and the Douleur Neuropathique
      4 (DN4) scale for neuropathic pain. Patients reported pain relief using a 4-point
      Likert scale (1=no relief; 4=important relief ). RESULTS: Nineteen patients (7
      females) with a median age of 55 (Q1-Q3; 44-58) underwent methadone rotation. The
      most common type of cancer was gastrointestinal. Seventeen patients had a
      diagnosis of mixed pain syndromes. Morphine equivalent daily dose (MEDD) prior to
      switching was 480 mg (Q1-Q3; 100-1021), and at least two nonmethadone opioid
      rotations had already been done for 13 patients. Between D0 and D7, the VAS score
      decreased by 4 points (p<0.001). The DN4 score became negative on D7 for 11 of 17
      patients (65%). On D7, 16 of 18 patients (89%) expressed moderate to greater than
      moderate pain relief. Methadone was discontinued in one patient on D7 because it
      was deemed ineffective and for 8 patients, who were unable to take oral drugs, it
      was discontinued after D14. CONCLUSION: Our results suggest that methadone is
      effective and well tolerated for refractory cancer pain.

PMID- 24116947
TI  - NMR studies of the dynamics of nitrophorin 2 bound to nitric oxide.
AB  - The Rhodnius nitrophorins are beta-barrel proteins of the lipocalin fold with a
      heme protruding from the open end of the barrel. They are found in the saliva of
      the blood-sucking insect Rhodnius prolixus, which synthesizes and stores nitric
      oxide (NO) in the salivary glands, where NO is bound to iron. NO is released by
      dilution and an increase in pH when the insect spits its saliva into the tissues
      of a victim, to aid in obtaining a blood meal. In the adult insect, there are
      four nitrophorins, NP1-NP4. At pH 7.3, NP4 releases NO 17 times faster than NP2
      does, as measured by stopped-flow kinetics. A number of crystal structures of the
      least abundant protein, NP4, are available. These structures have been used to
      propose that two loops between adjacent beta-strands at the front opening of the
      protein, the A-B and G-H loops, determine the rate of NO release. To learn how
      the protein loops contribute to the release of NO for each of the nitrophorins,
      the dynamics of these proteins are being studied in our laboratory. In this work,
      the NP2-NO complex has been investigated by nuclear magnetic resonance relaxation
      measurements to probe the picosecond-to-nanosecond and microsecond-to-millisecond
      time scale motions at three pH values, 5.0, 6.5, and 7.3. It is found that at pH
      5.0 and 6.5, the NP2-NO complex is rigid and only a few residues in the loop
      regions show dynamics, while at pH 7.3, somewhat more dynamics, particularly of
      the A-B loop, are observed. Comparison to other lipocalins shows that all are
      relatively rigid, and that the dynamics of lipocalins in general are much more
      subtle than those of mainly alpha-helical proteins. 

PMID- 24116949
TI  - HfO(2) on MoS(2) by atomic layer deposition: adsorption mechanisms and thickness
      scalability.
AB  - We report our investigation of the atomic layer deposition (ALD) of HfO2 on the
      MoS2 surface. In contrast to previous reports of conformal growth on MoS2 flakes,
      we find that ALD on MoS2 bulk material is not uniform. No covalent bonding
      between the HfO2 and MoS2 is detected. We highlight that individual precursors do
      not permanently adsorb on the clean MoS2 surface but that organic and solvent
      residues can dramatically change ALD nucleation behavior. We then posit that
      prior reports of conformal ALD deposition on MoS2 flakes that had been exposed to
      such organics and solvents likely rely on contamination-mediated nucleation.
      These results highlight that surface functionalization will be required before
      controllable and low defect density high-kappa/MoS2 interfaces will be realized.
      The band structure of the HfO2/MoS2 system is experimentally derived with valence
      and conduction band offsets found to be 2.67 and 2.09 eV, respectively. 

PMID- 24116948
TI  - In vitro and in vivo anti-tumour effects of MPT0B014, a novel derivative
      aroylquinoline, and in combination with erlotinib in human non-small-cell lung
      cancer cells.
AB  - BACKGROUND AND PURPOSE: The purpose of the current study was to assess a novel
      anti-cancer drug, MPT0B014, which is not a substrate for the P-glycoprotein (P
      gp) transporter, alone and in combination with erlotinib, against human non-small
      cell lung cancer (NSCLC). EXPERIMENTAL APPROACH: Cytotoxicity in human NSCLC cell
      lines was assessed by sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays. Cell cycle phase distributions were estimated
      with FACScan flow cytometry. Protein expression was detected by Western blotting
      analysis. Efflux of rhodamine 123 or calcein-acetoxymethylester was used to study
      the P-gp profile. The A549 xenograft model in mice was used to assess in vivo
      anti-tumour activity. KEY RESULTS: MPT0B014 showed potent anti-proliferative
      activity against A549, H1299 and H226 cells. It induced G2/M arrest with down
      regulation of Cdc (Tyr15) and Cdc25C, and up-regulation of cyclin B1, phospho
      Cdc2 (Thr161) and Aurora A/B. P-gp-overexpressing National Cancer
      Institute/Adriamycin-Resistant cells were also sensitive to B014. B014-induced
      loss of Mcl-1 was accompanied by activation of caspases-3, -7, -8 and -9, and
      initiation of apoptosis. B014 in combination with erlotinib caused significant
      tumour inhibition in vitro and in vivo. CONCLUSIONS AND IMPLICATIONS: MPT0B014
      exerted cytotoxicity against human NSCLC cell lines with little susceptibility to
      P-gp. Combined with the EGF receptor inhibitor, erlotinib, MPT0B014 exerted
      significant growth inhibition of A549 cells both in vitro and in vivo. B014 could
      be useful as an anti-cancer agent.

PMID- 24116951
TI  - Prospective study of activities of daily living outcomes in children with
      cerebellar atrophy.
AB  - AIM: The aim of this study was to identify clinical and radiological predictors
      of activities of daily living (ADL) outcomes in children with cerebellar atrophy.
      METHOD: Over a period of 5 years, we evaluated 44 participants (25 males, 19
      females) children with confirmed cerebellar atrophy using magnetic resonance
      imaging (MRI). The median age at the time of assessment 9 years; range 16 mo-18y.
      Participants were grouped according to whether the cerebellar atrophy was
      isolated or associated with other radiological abnormalities. Severity of
      cerebellar atrophy was graded using qualitative and quantitative scoring systems.
      A standardized ADL assessment was used to characterize functional outcomes. The
      characteristics of the participants were analysed using descriptive statistics.
      RESULTS: The mean age at symptom onset was 20 months (range birth-10y). The group
      with isolated cerebellar atrophy had better outcomes than the group with
      cerebellar atrophy associated with other radiological abnormalities, with a mean
      total ADL score difference of 8.0 points (95% confidence interval 1.8-14.2
      points, p=0.01). Age at onset of cerebellar atrophy before 2 years of age,
      progression of cerebellar atrophy on magnetic resonance imaging, presence of
      seizures, and decreased size of transverse cerebellar hemisphere diameter were
      all associated with worse outcomes. INTERPRETATION: We present a prospective
      study of clinical and radiological predictors of ADL outcome in children with
      cerebellar atrophy. This information may be useful in the diagnosis and future
      management of this complex group of disorders.

PMID- 24116950
TI  - Biodistribution of fluorescently labeled PAMAM dendrimers in neonatal rabbits:
      effect of neuroinflammation.
AB  - Dendrimers are being explored in many preclinical studies as drug, gene, and
      imaging agent delivery systems. Understanding their detailed organ, tissue,
      cellular uptake, and retention can provide valuable insights into their
      effectiveness as delivery vehicles and the associated toxicity. This work
      explores a fluorescence-quantification based assay that enables simultaneous
      quantitative biodistribution and imaging of dendrimers with a single agent. We
      have labeled an ethylenediamine-core generation-4 hydroxyl-terminated
      poly(amidoamine) (PAMAM) dendrimer using the fluorescent photostable, near-IR
      cyanine dye (Cy5) and performed quantitative and qualitative biodistribution of
      the dendrimer-Cy5 conjugates (D-Cy5) in healthy neonatal rabbits and neonatal
      rabbits with cerebral palsy (CP). The biodistribution of D-Cy5 and free Cy5 dye
      was evaluated in newborn rabbits, based on the developed quantification methods
      using fluorescence spectroscopy, high-performance liquid chromatography (HPLC),
      and size exclusion chromatography (SEC) and supported by microscopic imaging. The
      uptake was assessed in the brain, heart, liver, lungs, kidneys, blood serum, and
      urine. Results obtained based on these three independent methods are in good
      agreement and indicate the fast renal clearance of D-Cy5 and free Cy5 with
      relatively higher organs accumulation of the D-Cy5 conjugate. Following systemic
      administration, the D-Cy5 mainly accumulated in kidneys and bladder at 24 h. The
      quantitative biodistribution is in good agreement with previous studies based on
      radiolabeling. These methods for dendrimers quantification are easier and more
      practical, provide excellent sensitivity (reaching 0.1 ng per gram of tissue),
      and allow for quantification of dendrimers in different organs over longer time
      periods without concerns for radioactive decay, while also enabling tissue and
      cellular imaging in the same animal. In kits with fetal-neuroinflammation induced
      CP, there was a significantly higher uptake of D-Cy5 in the brain, while
      biodistribution in other organs was similar to that of healthy kits. 

PMID- 24116953
TI  - Optimal moth eye nanostructure array on transparent glass towards broadband
      antireflection.
AB  - Broadband antireflection (AR) is essential for improving the photocurrent
      generation of photovoltaic modules or the enhancement of visibility in optical
      devices. Beyond conventional AR coating methods, moth eye mimicking
      nanostructures give new directions to enhance broadband antireflection through
      the selection of geometrical parameters, such as height, periodic distance,
      shape, and arrangement. This study numerically and experimentally investigates
      the behavior of light on complex nanostructures designed to mimic the surface of
      the moth eye with mixed shapes and various arrangements. To obtain broadband AR,
      we rigorously study the design parameters, such as height, periodic distance,
      shape, and arrangement, on a transparent quartz substrate. Several kinds of
      nanopillar arrays are elaborately fabricated including mixed nanostructures
      comprising pointy and round shapes in ordered and random arrangements via
      colloidal lithography. The optimal morphology of moth eye nanostructure arrays
      for broadband antireflection is suggested in view of reflectance and average
      weight transmittance. 

PMID- 24116954
TI  - Feasibility and acceptability of Project Connect: a couples-based HIV-risk
      reduction intervention among young couples in Johannesburg, South Africa.
AB  - Given the importance of couples to the transmission of HIV, interventions
      focusing on both members of a partnership can play an important role in its
      prevention. We adapted and pilot-tested Project Connect, an evidence-based HIV
      prevention intervention for couples, to determine its acceptability and
      feasibility among a sample of young urban South African couples. We recruited
      couples from a clinic in inner-city Johannesburg to take part in the study.
      Interviewer-administered questionnaires were conducted at baseline and
      postintervention; an in-depth interview (IDI) was also conducted
      postintervention. Of 75 couples screened, 15 were eligible and enrolled. An
      important reason for ineligibility was a recent history of intimate partner
      violence (IPV). Couples attended, on average, five of the seven sessions.
      Overall, the intervention was acceptable and showed signs of potential efficacy.
      Couples reported enjoying Connect and feeling comfortable with its content.
      Participants also reported learning important communication and problem-solving
      skills, which resulted in more effective engagement in HIV prevention behaviors.
      However, the number of sessions and strict eligibility criteria proved
      challenging to the feasibility of the study. We recommend future couples'
      interventions have fewer sessions and enroll couples with a history of IPV. 

PMID- 24116956
TI  - Melanoma differentiation-associated gene 5 in zebrafish provoking higher
      interferon-promoter activity through signalling enhancing of its shorter splicing
      variant.
AB  - Melanoma differentiation-associated gene 5 (MDA5) is one of the three members in
      the retinoic acid-inducible gene I-like receptor (RLR) family, which are
      cytoplasmic pathogen recognition receptors recognizing intracellular viruses. In
      the present study, MDA5 and its spliced shorter forms, named as MDA5a and MDA5b,
      were identified in zebrafish. MDA5a and MDA5b can be up-regulated in cell lines
      following the infection of a negative ssRNA virus, the spring viraemia of carp
      virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella
      tarda, implying that the RLR may also be able to sense elements released from
      bacteria. The over-expression of MDA5a and MDA5b in fish cells resulted in
      significant induction of type I interferon promoter activity and enabled the
      protection of transfected cells against SVCV infection. Furthermore, the shorter
      spliced form, MDA5b when co-transfected with MDA5a or mitochondrial antiviral
      signalling protein (MAVS), induced a significantly higher level of interferon
      promoter activity, indicating that MDA5b may function as an enhancer in the
      interaction between MDA5 and MAVS. 

PMID- 24116957
TI  - CD19 as a therapeutic target in a spontaneous autoimmune polyneuropathy.
AB  - Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knock-out non-obese diabetic
      (NOD) mice is mediated by myelin protein zero (P0)-reactive T helper type 1 (Th1)
      cells. In this study, we investigated the role of B cells in SAP, focusing on
      CD19 as a potential therapeutic target. We found that P0-specific plasmablasts
      and B cells were increased in spleens of SAP mice compared to wild-type NOD mice.
      Depletion of B cells and plasmablasts with anti-CD19 monoclonal antibody (mAb)
      led to attenuation of disease severity when administered at 5 months of age. This
      was accompanied by decreased serum immunoglobulin (Ig)G and IgM levels, depletion
      of P0-specific plasmablasts and B cells, down-regulation/internalization of
      surface CD19 and increased frequency of CD4(+) regulatory T cells in spleens. We
      conclude that B cells are crucial to the pathogenesis of SAP, and that CD19 is a
      promising B cell target for the development of disease-modifying agents in
      autoimmune neuropathies. 

PMID- 24116960
TI  - Dicyclopalladated complexes of asymmetrically substituted azobenzenes: synthesis,
      kinetics and mechanisms.
AB  - Two series of new dicyclopalladated complexes {(DMF)PdCl(MU
      R(1)C6H3N?NC6H3R(2))PdCl(DMF)} of 4,4'-functionalized azobenzenes with
      substituents of varying electron-donating or electron-withdrawing strength (R(1)
      = H, NMe2; R(2) = H, Cl, Br, I, OMe, PhNH, CO2H, SO3Na, or NO2) have been
      synthesized and fully characterized. (1)H NMR spectroscopy along with the ESI
      mass spectrometry unambiguously identified the new complexes in the solution, and
      their solid-state structures were determined by X-ray crystallography. The
      presence of easily exchangeable solvent ligands was confirmed by (1)H NMR
      spectroscopy, X-ray experiments, and ESI mass spectrometry. The complexes were
      additionally characterized by UV-vis and fluorescence spectroscopies. The effect
      of different 4,4'-substituents on the formation rate of mono- and
      dicyclopalladated azobenzenes was studied by UV-vis spectroscopy. The
      experimental results are complemented by the quantum-chemical (DFT) calculations
      in order to rationalize the kinetic results as well as substituent effects on the
      reaction rates. It was found that the mono- and dicyclopalladation reactions of
      azobenzenes proceed in two consecutive processes, adduct formation and
      palladation steps. The rate-determining step in both palladations is the breaking
      of the ortho C-H bond, which has been confirmed as an electrophilic substitution
      process by Hammett correlations and DFT calculations. 

PMID- 24116958
TI  - Lennox-Gastaut syndrome of unknown cause: phenotypic characteristics of patients
      in the Epilepsy Phenome/Genome Project.
AB  - PURPOSE: Lennox-Gastaut syndrome (LGS) is a devastating childhood-onset epilepsy
      syndrome. The cause is unknown in 25% of cases. Little has been described about
      the specific clinical or electroencephalography (EEG) features of LGS of unknown
      or genetic cause (LGS(u)). The Epilepsy Phenome/Genome Project (EPGP) aims to
      characterize LGS(u) by phenotypic analysis of patients with LGS(u) and their
      parents. METHODS: One hundred thirty-five patients with LGS with no known
      etiology and their parents were enrolled from 19 EPGP centers in the United
      States and Australia. Clinical data from medical records, standardized
      questionnaires, imaging, and EEG were collected with use of online informatics
      systems developed for EPGP. KEY FINDINGS: LGS(u) in the EPGP cohort had a broad
      range of onset of epilepsy from 1 to 13 years, was male predominant (p < 0.0002),
      and was associated with normal development prior to seizure onset in 59.2% of
      patients. Despite the diagnosis, almost half of the adult patients with LGS(u)
      completed secondary school. Parents were cognitively normal. All subjects had EEG
      recordings with generalized epileptiform abnormalities with a spike wave
      frequency range of 1-5 Hz (median 2 Hz), whereas 8.1% of subjects had EEG studies
      with a normal posterior dominant rhythm. Almost 12% of patients evolved from West
      syndrome. SIGNIFICANCE: LGS(u) has distinctive characteristics including a broad
      age range of onset, male predominance, and often normal development prior to the
      onset of seizures. Cognitive achievements such as completion of secondary school
      were possible in half of adult patients. Our phenotypic description of LGS(u)
      coupled with future genetic studies will advance our understanding of this
      epilepsy syndrome.

PMID- 24116959
TI  - Transition to ustekinumab in patients with moderate-to-severe psoriasis and
      inadequate response to methotrexate: a randomized clinical trial (TRANSIT).
AB  - BACKGROUND: Limited data exist on transitioning patients with psoriasis from
      conventional systemic agents to biologics. OBJECTIVES: The TRANSIT study aimed to
      assess the efficacy and safety of two methotrexate-to-ustekinumab transition
      strategies. METHODS: Patients with moderate-to-severe psoriasis and inadequate
      methotrexate response were randomized 1 : 1 to receive ustekinumab with immediate
      (arm 1) or 4-week gradual (arm 2) methotrexate withdrawal. Patients weighing <=
      100 kg or > 100 kg received ustekinumab 45 mg or 90 mg, respectively. The primary
      endpoint was the frequency of adverse events (AEs) at week 12. Secondary
      endpoints included additional safety, efficacy and patient-reported outcomes. We
      report the 12-week efficacy and safety results. RESULTS: Overall, 244 patients in
      arm 1 and 245 in arm 2 were randomized and received ustekinumab. Four patients
      per arm discontinued the trial by week 12. At week 12 in arms 1 and 2,
      respectively, 61% and 65% of patients experienced an AE, 2.9% and 2.4% had a
      serious AE, and 1.2% and 0.4% had an AE leading to ustekinumab discontinuation.
      In arms 1 and 2, respectively, median Psoriasis Area and Severity Index (PASI)
      score decreased from 15.2 and 15.4 at baseline to 2.9 and 2.8 at week 12; 58% and
      62% of patients achieved a 75% reduction from baseline in PASI score (PASI 75) at
      week 12; median baseline Dermatology Life Quality Index fell from 8 and 9 at
      baseline to 1 (both arms) at week 16. CONCLUSIONS: Ustekinumab was well tolerated
      and effective in patients who had an inadequate response to methotrexate. Both
      transition strategies resulted in similar week 12 safety and efficacy outcomes.

PMID- 24116961
TI  - Insights into the implementation and operation of a novel paramedic long-term
      care program.
AB  - OBJECTIVE: An extended-care paramedic (ECP) program was implemented to provide
      emergency assessment and care on site to long-term care (LTC) residents suffering
      acute illness or injury. A single paramedic works collaboratively with
      physicians, LTC staff, patient, and family to develop care plans to address acute
      situations, often avoiding the need to transport the resident to hospital. We
      sought to identify insights gained and lessons learned during implementation and
      operation of this novel program. METHODS: The perceptions and experiences of
      various stakeholders were explored in focus groups, using a semi-structured
      interview guide. Two investigators independently conducted thematic analysis and
      identified emerging themes and related codes. Congruence and differences were
      discussed to achieve consensus. RESULTS: Twenty-one participants took part in
      four homogeneous focus groups: paramedics and dispatchers, ECPs, ECP oversight
      physicians, and decision-makers. The key themes identified were (1) program
      implementation, (2) ECP process of care, (3) communications, and (4) end-of-life
      care. CONCLUSION: The ECP program has positive implications for the relationship
      between EMS and LTC, requires additional paramedic training, and can positively
      affect LTC patient experiences during acute medical events. ECPs have a novel
      role to play in end-of-life care and find this new role rewarding.

PMID- 24116963
TI  - Adolescent birth rates in Greece: features and recent unfavorable trends.

PMID- 24116964
TI  - Clinical aspects of medication overuse headaches.
AB  - Medication overuse headache (MOH) is a subset of chronic daily headache,
      occurring from overuse of 1 or more classes of migraine abortive medication.
      Acetaminophen, combination analgesics (caffeine combinations), opioids,
      barbiturates (butalbital), non-steroidal anti-inflammatory drugs, and triptans
      are the main classes of drugs implicated in the genesis of MOH. Migraine seems to
      be the most common diagnosis leading to MOH. The development of MOH is associated
      with both frequency of use of medication and behavioral predispositions. MOH is
      not a unitary concept. The distinction between simple (type 1) vs complex (type
      2) forms is based on both the class of overused medication and behavioral
      factors, including psychopathology and psychological drug dependence. MOH is a
      challenging disorder causing decline in the quality of life and causing physical
      symptoms, such as daily and incapacitating headaches, insomnia, and non
      restorative sleep, as well as psychological distress and reduced functioning. MOH
      is associated with biochemical, structural, and functional brain changes. Relapse
      after detoxification is a challenge, but can be addressed if the patient is
      followed over a prolonged period of time with a combination of prophylactic
      pharmacotherapy, use of abortive medication with minimal risk of MOH, withholding
      previously overused medication, and providing psychological (cognitive
      behavioral) therapy. 

PMID- 24116965
TI  - U.S. selected practice recommendations for contraceptive use, 2013.
AB  - Unintended pregnancy rates remain high in the United States and these pregnancies
      may carry increased risks for negative health outcomes. Lack of contraceptive use
      and inconsistent use are important contributors to the high rate of unintended
      pregnancies. Women may face certain barriers to starting contraception and using
      it effectively. The Centers for Disease Control and Prevention has recently
      developed the U.S. Selected Practice Recommendations for Contraceptive Use, 2013,
      which provides guidance for common yet sometimes complex issues in contraceptive
      management. This guidance aims to reduce barriers to contraceptive use by
      providing clear recommendations for providers to assist women in initiating and
      using contraceptive methods to maximize effectiveness and decrease risk of
      unintended pregnancy.

PMID- 24116962
TI  - Development of pharmacological strategies for mitochondrial disorders.
AB  - Mitochondrial diseases are an unusually genetically and phenotypically
      heterogeneous group of disorders, which are extremely challenging to treat.
      Currently, apart from supportive therapy, there are no effective treatments for
      the vast majority of mitochondrial diseases. Huge scientific effort, however, is
      being put into understanding the mechanisms underlying mitochondrial disease
      pathology and developing potential treatments. To date, a variety of treatments
      have been evaluated by randomized clinical trials, but unfortunately, none of
      these has delivered breakthrough results. Increased understanding of
      mitochondrial pathways and the development of many animal models, some of which
      are accurate phenocopies of human diseases, are facilitating the discovery and
      evaluation of novel prospective treatments. Targeting reactive oxygen species has
      been a treatment of interest for many years; however, only in recent years has it
      been possible to direct antioxidant delivery specifically into the mitochondria.
      Increasing mitochondrial biogenesis, whether by pharmacological approaches,
      dietary manipulation or exercise therapy, is also currently an active area of
      research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial
      membrane lipid milieu have also emerged as possible treatment strategies. Recent
      technological advances in gene therapy, including allotopic and transkingdom gene
      expression and mitochondrially targeted transcription activator-like nucleases,
      have led to promising results in cell and animal models of mitochondrial
      diseases, but most of these techniques are still far from clinical application.

PMID- 24116966
TI  - The status of HIV prevention efforts for women in correctional facilities.
AB  - In the United States, women are a significant proportion of the correctional
      population. Women also account for an increasing proportion of newly diagnosed
      human immunodeficiency virus (HIV) cases. When compared with white women, black
      women have higher incarceration rates and represent more of the newly diagnosed
      HIV cases. Correctional facilities offer an opportunity to provide women with HIV
      testing and prevention services so that they will know their status and receive
      HIV/sexually transmitted disease (STD) risk-reduction counseling and other
      preventive services. In this report, we describe incarcerated population
      statistics and HIV surveillance epidemiology for women. We also describe HIV
      prevention activities undertaken by the Centers for Disease Control and
      Prevention's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB
      Prevention. Additional research, program development, and implementation are
      needed to improve HIV prevention efforts for high-risk women.

PMID- 24116967
TI  - Advancing adolescent sexual and reproductive health by promoting healthy
      relationships.
AB  - The field of public health faces a challenge in preventing adverse sexual and
      reproductive health outcomes such as sexually transmitted diseases, unintended
      pregnancy, and dating and sexual violence among adolescents. Innovative
      approaches are needed to better address these issues. Focusing on healthy
      relationships is an emerging approach that may be used to promote adolescent
      sexual and reproductive health. In this report, we discuss the need for
      innovative and efficient strategies for adolescent sexual and reproductive
      health, the benefits of a healthy relationships approach, describe the need for a
      science-based conceptual framework on healthy relationships, and provide some
      considerations for developing a conceptual framework of healthy relationships in
      order to move the field of public health forward.

PMID- 24116968
TI  - Stereochemistry of the tadalafil diastereoisomers: a critical assessment of
      vibrational circular dichroism, electronic circular dichroism, and optical
      rotatory dispersion.
AB  - The stereochemistry of all four stereoisomers of tadalafil is determined using
      vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and
      optical rotatory dispersion (ORD) spectroscopy. By comparing experimentally
      obtained VCD spectra to computationally simulated ones, the absolute
      configuration of the enantiomeric pair (6R, 12aR)/(6S, 12aS) can be confidently
      assigned without prior knowledge of their relative stereochemistry. IR and NMR
      spectra are used to aid the assignment of the relative stereochemistry. The IR
      and VCD difference spectra further confirm the assignment of all stereoisomers.
      ECD and ORD spectra are used to investigate the complementarity of the three
      chiroptical techniques. VCD spectroscopy itself is found to have the ability to
      identify diastereoisomers, and simultaneous use of these chiroptical
      spectroscopic methods and NMR chemical shifts aids in increasing the reliability
      of stereochemistry assignment of diastereoisomers. 

PMID- 24116969
TI  - Association between childhood obesity, cognitive development, physical fitness
      and social-emotional wellbeing in a transitional economy.
AB  - BACKGROUND: It has been suggested that obese children have lower cognitive
      function, demonstrate poorer physical performance and are more susceptible to
      social-emotional problems. AIMS: To describe associations between human physical
      growth, cognitive development, physical fitness and social-emotional
      characteristics of obese and non-obese children and to verify the predictors of
      intellectual coefficient by socioeconomic status (SES). SUBJECTS AND METHODS: A
      sample of 107 non-obese (N-Ob) children [-1 z-score body mass index (BMI) <=1 z
      score] and 108 obese (Ob) children [2 z-score <=BMI <=5 z-score] from a larger
      cohort was evaluated. Intellectual coefficient (IQ), social-emotional wellbeing
      (SEW), 6-minute walk test (6MWT) and SES (mid-low, low and very low) were
      assessed. RESULTS: Ob children were taller, heavier and present more height for
      age and BMI than N-Ob children (p < 0.001). A significant correlation between IQ
      and SEW (r = 0.14), 6MWT and BMI z-score (r = -0.18) and 6MWT and SEW (r = 0.15)
      was found. Multiple regression analysis revealed that BMI z-score had a negative
      impact on IQ in the mid-low SES sub-group and that SEW had a positive effect on
      IQ in the very-low SES sub-group. CONCLUSIONS: In Chilean pre-school children
      from low-income families cognitive ability varied according to SES.

PMID- 24116970
TI  - Alu-mediated large deletion of the CDSN gene as a cause of peeling skin disease.
AB  - Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by
      mutations in CDSN and is characterized by superficial peeling of the upper
      epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that
      plays an important role in maintaining epidermis integrity. Herein, we report a
      patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region
      encompassing the CDSN gene, which abrogates CDSN expression. Several genes
      including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted,
      however, the patient showed only clinical features typical of PSD. The deletion
      size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that
      both telomeric and centromeric breakpoints existed within Alu-S sequences that
      were oriented in opposite directions. These results suggest an Alu-mediated
      recombination event as the mechanism underlying the deletion in our patient. 

PMID- 24116971
TI  - Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2
      regulated antioxidant enzyme expression in LPS-induced murine peritoneal
      macrophages.
AB  - BACKGROUND AND PURPOSE: Increasing evidence demonstrates that melatonin regulates
      inflammatory and immune processes acting as both an activator and inhibitor of
      these responses. Nevertheless, the molecular mechanisms of its anti-inflammatory
      action remain unclear. Here we have characterized the cellular mechanisms
      underlying the redox modulation of LPS-stimulated inflammatory responses in
      murine peritoneal macrophages by melatonin to provide insight into its anti
      inflammatory effects. EXPERIMENTAL APPROACH: Murine peritoneal macrophages were
      isolated and treated with melatonin in the presence or absence of LPS (5 MUg.mL(
      1) ) for 18 h. Cell viability was determined using sulforhodamine B assay and NO
      production was measured using the Griess reaction. Pro-inflammatory enzymes and
      transcription factors were detected by Western blotting. KEY RESULTS: Without
      affecting cell viability, melatonin (12.5, 25, 50 and 100 MUM) reduced the level
      of nitrites, inducible NOS (iNOS), COX-2 and microsomal PGE synthase-1 (mPGES1)
      protein, and p38 MAPK phosphorylation, and prevented NF-kappaB translocation.
      Furthermore, melatonin treatment significantly increased NF-E2-related factor 2
      (Nrf2) and haem oxygenase 1 (HO1) protein levels in murine macrophages exposed to
      LPS. CONCLUSIONS AND IMPLICATIONS: Melatonin reduced pro-inflammatory mediators
      and enhanced the expression of HO1 via NF-kappaB, p38 MAPK and Nrf2 cascade
      signalling pathways in murine macrophages. Thus, melatonin might be a promising
      target for diseases associated with overactivation of macrophages.

PMID- 24116973
TI  - The effects of safety checklists in medicine: a systematic review.
AB  - BACKGROUND: Safety checklists have become an established safety tool in medicine.
      Despite studies showing decreased mortality and complications, the effects and
      feasibility of checklists have been questioned. This systematic review summarises
      the medical literature aiming to show the effects of safety checklists with a
      number of outcomes. METHODS: The Preferred Reporting Items for Systematic Review
      and Meta-Analysis (PRISMA) statement was used. All studies in which safety
      checklists were used as an additional tool designed to assure that an operation
      or task was performed as planned were included. RESULTS: The initial search
      extracted 7408 hits. Twenty-nine articles met the inclusion criteria. Five
      additional studies were identified by a cross-referencing search. Four groups
      were made according to outcome measures. One group (n = 7) had 'hard' outcome
      measures, such as mortality and morbidity. The remaining studies, reporting
      'softer' process-related measures, were divided into three categories: adherence
      to guidelines (n = 6), human factors (n = 16), and reduction of adverse events (n
      = 5). The main findings were improved communication, reduced adverse events,
      better adherence to standard operating procedures, and reduced morbidity and
      mortality. None of the included studies reported decreased patient safety or
      quality after introducing safety checklists. CONCLUSION: Safety checklists appear
      to be effective tools for improving patient safety in various clinical settings
      by strengthening compliance with guidelines, improving human factors, reducing
      the incidence of adverse events, and decreasing mortality and morbidity. None of
      the included studies reported negative effects on safety.

PMID- 24116974
TI  - Hybrid composite Ni(OH)2@NiCo2O4 grown on carbon fiber paper for high-performance
      supercapacitors.
AB  - We have successfully fabricated and tested the electrochemical performance of
      supercapacitor electrodes consisting of Ni(OH)2 nanosheets coated on NiCo2O4
      nanosheets grown on carbon fiber paper (CFP) current collectors. When the NiCo2O4
      nanosheets are replaced by Co3O4 nanosheets, however, the energy and power
      density as well as the rate capability of the electrodes are significantly
      reduced, most likely due to the lower conductivity of Co3O4 than that of NiCo2O4.
      The 3D hybrid composite Ni(OH)2/NiCo2O4/CFP electrodes demonstrate a high areal
      capacitance of 5.2 F/cm(2) at a cycling current density of 2 mA/cm(2), with a
      capacitance retention of 79% as the cycling current density was increased from 2
      to 50 mA/cm(2). The remarkable performance of these hybrid composite electrodes
      implies that supercapacitors based on them have potential for many practical
      applications. 

PMID- 24116972
TI  - K137R mutation on adeno-associated viral capsids had minimal effect on enhancing
      gene delivery in vivo.
AB  - The adeno-associated viral (AAV) vector has emerged as an attractive vector for
      gene therapy applications. Development of AAV vectors with enhanced gene
      transduction efficiency is important to ease the burden of AAV production and
      minimize potential immune responses. Rational mutations on AAV capsids have
      gained attention as a simple method of enhancing AAV transduction efficiency. A
      single-amino acid mutation, K137R, on AAV1 and AAV8 was recently reported to
      increase liver transgene expression by 5-10-fold. To determine whether the same
      mutation on other AAV serotypes would result in similar gene enhancement effects,
      K137R mutants were generated on AAV7, AAV8, and AAV9, and their effects were
      evaluated in vivo. Two reporter genes were utilized: the nuclear LacZ gene driven
      by the cytomegalovirus promoter and the luciferase gene driven by the CB
      promoter. Surprisingly, we found no difference in luciferase gene expression in
      the liver or other tissues using either the wild-type AAV8 capsid or AAV8-K137R.
      LacZ gene expression in the liver by AAV8-K137R was about onefold higher than
      that of wild-type AAV8. However, no difference was found in other tissues, such
      as skeletal muscle and cardiac muscle. In addition, no difference was found in
      transgene expression with either AAV7-K137R or AAV9-K137R mutants. Our results
      indicated that the K137R mutation on AAV7, AAV8, and AAV9 had minimal to no
      effect on transduction efficiency in vivo.

PMID- 24116975
TI  - Control of radiation damage in MoS(2) by graphene encapsulation.
AB  - Recent dramatic progress in studying various two-dimensional (2D) atomic crystals
      and their heterostructures calls for better and more detailed understanding of
      their crystallography, reconstruction, stacking order, etc. For this, direct
      imaging and identification of each and every atom is essential. Transmission
      electron microscopy (TEM) and scanning transmission electron microscopy (STEM)
      are ideal and perhaps the only tools for such studies. However, the electron beam
      can in some cases induce dramatic structure changes, and radiation damage becomes
      an obstacle in obtaining the desired information in imaging and chemical analysis
      in the (S)TEM. This is the case of 2D materials such as molybdenum disulfide
      MoS2, but also of many biological specimens, molecules, and proteins. Thus,
      minimizing damage to the specimen is essential for optimum microscopic analysis.
      In this article we demonstrate, on the example of MoS2, that encapsulation of
      such crystals between two layers of graphene allows for a dramatic improvement in
      stability of the studied 2D crystal and permits careful control over the defect
      nature and formation in it. We present STEM data collected from single-layer MoS2
      samples prepared for observation in the microscope through three distinct
      procedures. The fabricated single-layer MoS2 samples were either left bare
      (pristine), placed atop a single-layer of graphene, or finally encapsulated
      between single graphene layers. Their behavior under the electron beam is
      carefully compared, and we show that the MoS2 sample "sandwiched" between the
      graphene layers has the highest durability and lowest defect formation rate
      compared to the other two samples, for very similar experimental conditions. 

PMID- 24116976
TI  - Why are some women with pelvic floor dysfunction unable to contract their pelvic
      floor muscles?
AB  - INTRODUCTION: Many women with pelvic floor dysfunction are unable to voluntarily
      contract their pelvic floor muscles. This study hypothesised that women who
      cannot contract their pelvic floor muscles, despite specialised pelvic floor
      physiotherapy, are likely to have avulsion defect of the levator ani muscle,
      visible on 3-dimensional ultrasound. METHODS: Pelvic floor muscle strength was
      assessed by modified Oxford scale in all women presenting to a tertiary
      urogynaecology clinic with a main complaint of urinary incontinence +/- pelvic
      organ prolapse. Women who could not contract their pelvic floor muscles (PFM)
      after having training with a specialised pelvic floor physiotherapist, (modified
      Oxford score of 0 or 1), were invited to participate in 3-dimensional
      transperineal ultrasound. RESULTS: Of 625 women presenting with urinary
      incontinence and/or pelvic organ prolapse, 150 (24.0%) were unable to contract
      their PFM at initial assessment. After specialised pelvic floor physiotherapy, 20
      of 150 (15.3%) could not contract and were termed 'noncontractors'. Of these, 12
      agreed to participate in transperineal ultrasound. Levator avulsion defects were
      detected in 8 of 12 (66.7%). CONCLUSION: Our results show that 67% of women who
      cannot contract their PFM despite physiotherapy have levator avulsion defects.
      The mechanism affecting the remaining 33% is yet to be discovered.

PMID- 24116977
TI  - Sleep difficulties after paediatric traumatic brain injury.

PMID- 24116979
TI  - Angiocentric glioma.

PMID- 24116978
TI  - Transforming growth factor beta-induced superficial zone protein accumulation in
      the surface zone of articular cartilage is dependent on the cytoskeleton.
AB  - The phenotype of articular chondrocytes is dependent on the cytoskeleton,
      specifically the actin microfilament architecture. Articular chondrocytes in
      monolayer culture undergo dedifferentiation and assume a fibroblastic phenotype.
      This process can be reversed by altering the actin cytoskeleton by treatment with
      cytochalasin. Whereas dedifferentiation has been studied on chondrocytes isolated
      from the whole cartilage, the effects of cytoskeletal alteration on specific
      zones of cells such as superficial zone chondrocytes are not known. Chondrocytes
      from the superficial zone secrete superficial zone protein (SZP), a lubricating
      proteoglycan that reduces the coefficient of friction of articular cartilage. A
      better understanding of this phenomenon may be useful in elucidating chondrocyte
      dedifferentiation in monolayer and accumulation of the cartilage lubricant SZP,
      with an eye toward tissue engineering functional articular cartilage. In this
      investigation, the effects of cytoskeletal modulation on the ability of
      superficial zone chondrocytes to secrete SZP were examined. Primary superficial
      zone chondrocytes were cultured in monolayer and treated with a combination of
      cytoskeleton modifying reagents and transforming growth factor beta (TGFbeta) 1,
      a critical regulator of SZP production. Whereas cytochalasin D maintains the
      articular chondrocyte phenotype, the hallmark of the superficial zone
      chondrocyte, SZP, was inhibited in the presence of TGFbeta1. A decrease in
      TGFbeta1-induced SZP accumulation was also observed when the microtubule
      cytoskeleton was modified using paclitaxel. These effects of actin and
      microtubule alteration were confirmed through the application of jasplakinolide
      and colchicine, respectively. As Rho GTPases regulate actin organization and
      microtubule polymerization, we hypothesized that the cytoskeleton is critical for
      TGFbeta-induced SZP accumulation. TGFbeta-mediated SZP accumulation was inhibited
      by small molecule inhibitors ML141 (Cdc42), NSC23766 (Rac1), and Y27632 (Rho
      effector Rho Kinase). On the other hand, lysophosphatidic acid, an upstream
      activator of Rho, increased SZP synthesis in response to TGFbeta1. These results
      suggest that SZP production is dependent on the functional cytoskeleton, and Rho
      GTPases contribute to SZP accumulation by modulating the actions of TGFbeta. 

PMID- 24116980
TI  - Occipital diploic cranial fasciitis after radiotherapy for a cerebellar
      medulloblastoma.
AB  - Radiation-induced cranial fasciitis is a rare complication of radiotherapy,
      especially in an intradiploic location. The authors report such a case of cranial
      fasciitis in a 13-year-old girl previously subjected to cranial radiotherapy for
      a recurrent cerebellar medulloblastoma. The patient had undergone a gross-total
      removal of a medulloblastoma followed by no radiation therapy at the age of 10
      years. The tumor recurred at the original site 2 years later, warranting a repeat
      operation with a gross-total tumor removal and subsequent radiation therapy. The
      follow-up MRI sequence demonstrated no abnormal appearance for 1 year, until a
      new enhancing mass was found within the occipital bone adjacent to the prior bone
      window. Following its resection, the new lesion was histologically identified as
      cranial fasciitis. Differential diagnosis of a well-circumscribed bone lesion
      should include cranial fasciitis, especially in young children with radiotherapy
      for a previous intracranial malignancy. Radiotherapy should be considered among
      the inciting factors in the development of cranial fasciitis. The osteolytic
      lesions of cranial fasciitis, although nontumoral and self-limited in duration,
      should be eligible candidates for early, total resection to avoid potential
      intracranial expansion. 

PMID- 24116981
TI  - No significant improvement in the rate of accurate ventricular catheter location
      using ultrasound-guided CSF shunt insertion: a prospective, controlled study by
      the Hydrocephalus Clinical Research Network.
AB  - OBJECT: Cerebrospinal fluid shunt ventricular catheters inserted into the frontal
      horn or trigone are associated with prolonged shunt survival. Developing surgical
      techniques for accurate catheter insertion could, therefore, be beneficial to
      patients. This study was conducted to determine if the rate of accurate catheter
      location with intraoperative ultrasound guidance could exceed 80%. METHODS: The
      authors conducted a prospective, multicenter study of children (< 18 years)
      requiring first-time treatment for hydrocephalus with a ventriculoperitoneal
      shunt. Using intraoperative ultrasound, surgeons were required to target the
      frontal horn or trigone for catheter tip placement. An intraoperative ultrasound
      image was obtained at the time of catheter insertion. Ventricular catheter
      location, the primary outcome measure, was determined from the first
      postoperative image. A control group of patients treated by nonultrasound
      surgeons (conventional surgeons) were enrolled using the same study criteria.
      Conventional shunt surgeons also agreed to target the frontal horn or trigone for
      all catheter insertions. Patients were triaged to participating surgeons based on
      call schedules at each center. A pediatric neuroradiologist blinded to method of
      insertion, center, and surgeon determined ventricular catheter tip location.
      RESULTS: Eleven surgeons enrolled as ultrasound surgeons and 6 as conventional
      surgeons. Between February 2009 and February 2010, 121 patients were enrolled at
      4 Hydrocephalus Clinical Research Network centers. Experienced ultrasound
      surgeons (> 15 cases prior to study) operated on 67 patients; conventional
      surgeons operated on 52 patients. Experienced ultrasound surgeons achieved
      accurate catheter location in 39 (59%) of 66 patients, 95% CI (46%-71%).
      Intraoperative ultrasound images were compared with postoperative scans. In 32.7%
      of cases, the catheter tip moved from an accurate location on the intraoperative
      ultrasound image to an inaccurate location on the postoperative study. This was
      the most significant factor affecting accuracy. In comparison, conventional
      surgeons achieved accurate location in 24 (49.0%) of 49 cases (95% CI [34%-64%]).
      The shunt survival rate at 1 year was 70.8% in the experienced ultrasound group
      and 66.9% in the conventional group (p = 0.66). Ultrasound surgeons had more
      catheters surrounded by CSF (30.8% vs 6.1%, p = 0.0012) and away from the choroid
      plexus (72.3% vs 58.3%, p = 0.12), and fewer catheters in the brain (3% vs 22.4%,
      p = 0.0011) and crossing the midline (4.5% vs 34.7%, p < 0.001), but they had a
      higher proportion of postoperative pseudomeningocele (10.1% vs 3.8%, p = 0.30),
      wound dehiscence (5.8% vs 0%, p = 0.13), CSF leak (10.1% vs 1.9%, p = 0.14), and
      shunt infection (11.6% vs 5.8%, p = 0.35). CONCLUSIONS: Ultrasound-guided shunt
      insertion as performed in this study was unable to consistently place catheters
      into the frontal horn or trigone. The technique is safe and achieves outcomes
      similar to other conventional shunt insertion techniques. Further efforts to
      improve accurate catheter location should focus on prevention of catheter
      migration that occurs between intraoperative placement and postoperative imaging.
      Clinical trial registration no.: NCT01007786 ( ClinicalTrials.gov ).

PMID- 24116982
TI  - Reduction in upper-extremity tone after lumbar selective dorsal rhizotomy in
      children with spastic cerebral palsy.
AB  - OBJECT: Randomized clinical trials have established that lumbar selective dorsal
      rhizotomy (SDR) reduces lower-extremity tone and improves functional outcome in
      children with spastic cerebral palsy. Significant data exist to support a
      secondary effect on upper-extremity function in patients with upper-extremity
      spasticity. The effects of SDR on upper-extremity tone, however, are not well
      characterized. In this report, the authors sought to assess changes in upper
      extremity tone in individual muscle groups after SDR and tried to determine if
      these changes could be predicted preoperatively. METHODS: The authors
      retrospectively reviewed 42 children who underwent SDR at Columbia University
      Medical Center/Morgan Stanley Children's Hospital of NewYork-Presbyterian between
      2005 and 2011. Twenty-five had upper-extremity spasticity. All underwent pre- and
      postoperative examination for measuring tone (Modified Ashworth Scale) and
      assessing functional outcome. Follow-up examinations with therapists were
      performed at least once at a minimum of 2 months postoperatively (mean 15
      months). RESULTS: In the upper extremities, 23 (92%) of 25 patients had
      improvements of at least 1 Ashworth point in 2 or more independent motor groups
      on the Modified Ashworth Scale, and 12 (71%) of 17 families surveyed reported
      increases in motor control or spontaneous movement. The mean Modified Ashworth
      Scale scores for all upper-extremity muscle groups demonstrated an improvement
      from 1.34 to 1.22 (p < 0.001). Patients with a mean preoperative upper-extremity
      tone of 1.25-1.75 were most likely to benefit from reduction in tone (p =
      0.0019). Proximal and pronator muscle groups were most likely to demonstrate
      reduced tone. CONCLUSIONS: In addition to improvements in lower-extremity tone
      and function, SDR has demonstrable effects on upper extremities. Greater than 90%
      of our patients with elevated upper-extremity tone demonstrated reduction in tone
      in at least 2 muscle groups postoperatively. Patients with a mean Modified
      Ashworth Scale upper-extremity score of 1.25-1.75 may encounter the greatest
      reduction in upper-extremity tone.

PMID- 24116983
TI  - Fevers and abnormal blood and cerebrospinal fluid studies after pediatric
      cerebral hemispherectomy: impact of etiology and age at surgery.
AB  - OBJECT: The object of this study was to determine if etiology and age at surgery
      were linked with fevers and altered white blood cell and CSF laboratory values
      after cerebral hemispherectomy. METHODS: Seizure etiologies (n = 76) were
      classified into hemimegalencephaly (HME), cortical dysplasia (CD), infarcts
      (stroke), Rasmussen encephalitis (RE), history of infections, and Sturge-Weber
      syndrome (SWS) and were compared with clinical variables, maximum daily
      temperature (Tmax), and blood and CSF studies through Day 12 posthemispherectomy.
      RESULTS: The Tmax on Days 2-4 and 9-12 postsurgery were higher for HME and RE
      cases than for stroke cases. Patients with RE showed positive correlations,
      whereas those with SWS had negative correlations between Tmax and age at surgery.
      Blood WBC counts on postsurgery Days 3, 6, and 9-12 were higher in the HME and CD
      cases than in the stroke and RE cases. The percentage of blood polymorphonuclear
      cells (%bloodPMNs) was higher in the RE cases than in the HME, CD, and SWS cases.
      The RE, HME, and CD cases showed positive correlations between %bloodPMNs and age
      at surgery. The percentage of blood monocytes (%bloodMono) was higher in the
      patients with HME than in those with stroke or RE. The HME and CD cases showed
      negative correlations between %bloodMono and age at surgery. The CSF red blood
      cell counts were higher in the RE than in the CD and stroke cases. The percentage
      of CSF monocytes was higher in patients with CD than in those with stroke and RE.
      The percentage of CSF lymphocytes positively correlated with age at surgery.
      CONCLUSIONS: Seizure etiology and age at surgery were associated with developing
      fevers and altered blood and CSF values after pediatric cerebral hemispherectomy.
      These findings indicate that besides infections, other clinical variables have an
      impact on developing fevers and abnormal laboratory values posthemispherectomy.
      Cultures appear to be the most reliable predictor of infections.

PMID- 24116984
TI  - Long-term outcomes of dorsal rhizotomy.

PMID- 24116985
TI  - Suboptimal awareness and comprehension of published preexposure prophylaxis
      efficacy results among physicians in Massachusetts.
AB  - In 2010, the centre for the AIDS Programme of Research in South Africa
      (CAPRISA)004 and iPrEx trials (microbicide gel containing tenofovir and oral pill
      containing tenofovir-emtricitabine, respectively) demonstrated that
      antiretroviral preexposure prophylaxis (PrEP) reduced the risk of HIV acquisition
      among high-risk individuals. To determine the facilitators and barriers to PrEP
      provision by health-care providers, we conducted an online, quantitative survey
      of Massachusetts-area physicians following the publication of the CAPRISA and
      iPrEx results. We assessed awareness and comprehension of efficacy data,
      prescribing experience, and anticipated provision of oral and topical PrEP among
      physicians, as well as demographic and behavioral factors associated with PrEP
      awareness and prescribing intentions. The majority of HIV specialists and
      generalist physicians were aware of data from these PrEP trials and able to
      correctly interpret the results, however, correct interpretation of findings
      tended to vary according to specialty (i.e., HIV specialists had greater
      awareness than generalists). In addition, provider concerns regarding PrEP
      efficacy and safety, as well its ability to divert funds from other HIV
      prevention resources, were associated with decreased intentions to prescribe both
      oral and topical PrEP. Findings suggest that a substantial proportion of
      physicians who may have contact with at-risk individuals may benefit from
      interventions that provide accurate data on the risks and benefits of PrEP in
      order to facilitate effective PrEP discussions with their patients. Future
      studies to develop and test interventions aimed at health-care providers should
      be prioritized to optimize implementation of PrEP in clinical settings.

PMID- 24116986
TI  - Experience of fetal scalp blood sampling during labor.
AB  - Fetal scalp blood sampling (FBS) is often claimed to be painful for women in
      labor and difficult for obstetricians to perform. Our aim was to assess women's
      experience of pain during FBS and obstetricians' experience of difficulty in
      performing the test. At a tertiary center in Sweden, a questionnaire with answers
      on a 10-point scale was completed by 51 women and the obstetricians performing
      the test. Women's experience of pain had a median of 3.5. FBS was well tolerated
      in women who had epidural analgesia but might be associated with pain in women
      without. Higher maternal body mass index and less cervical dilation were
      associated with higher pain ratings. Obstetricians did not generally experience
      scalp sampling as difficult to perform (median score 3.0). However, the sampling
      procedure can be more complicated in situations with higher maternal body mass
      index, less cervical dilation, and a higher station of the fetal head. 

PMID- 24116987
TI  - Size-dependent and step-modulated supramolecular electrochemical properties of
      catechol-derived adlayers at Pt(hkl) surfaces.
AB  - The electrochemical reactivity of catechol-derived adlayers is reported at
      platinum (Pt) single-crystal electrodes. Pt(111) and stepped vicinal surfaces are
      used as model surfaces possessing well-ordered nanometer-sized Pt(111) terraces
      ranging from 0.4 to 12 nm. The electrochemical experiments were designed to probe
      how the control of monatomic step-density and of atomic-level step structure can
      be used to modulate molecule-molecule interactions during self-assembly of
      aromatic-derived organic monolayers at metallic single-crystal electrode
      surfaces. A hard sphere model of surfaces and a simplified band formation model
      are used as a theoretical framework for interpretation of experimental results.
      The experimental results reveal (i) that supramolecular electrochemical effects
      may be confined, propagated, or modulated by the choice of atomic level
      crystallographic features (i.e.monatomic steps), deliberately introduced at
      metallic substrate surfaces, suggesting (ii) that substrate-defect engineering
      may be used to tune the macroscopic electronic properties of aromatic molecular
      adlayers and of smaller molecular aggregates.

PMID- 24116988
TI  - Development of mycosis fungoides after bone marrow transplantation for chronic
      myeloid leukaemia: transmission from an allogeneic donor.
AB  - We report on a patient who developed donor-derived cutaneous T-cell lymphoma
      (CTCL) 4 years after successful treatment of chronic myeloid leukaemia with an
      allogeneic bone marrow transplant. The patient developed an eczematous rash
      unresponsive to topical therapy and immunosuppression. When CTCL was diagnosed in
      the recipient, his sibling donor had been attending his local dermatology unit
      with a maculosquamous rash, which proved subsequently to be mycosis fungoides. An
      identical pattern of donor and recipient clonality assessment and T-cell receptor
      gene sequencing indicated that the CTCL was probably transmitted in the bone
      marrow harvest. This suggests that CTCL cells circulate in the marrow at an early
      subclinical stage in this disease. This is the second case of donor-derived CTCL
      reported to date.

PMID- 24116989
TI  - Electron-deficient ternary and quaternary pnictides Rb4Zn7As7, Rb4Mn3.5Zn3.5Sb7,
      Rb7Mn12Sb12, and Rb7Mn4Cd8Sb12 with corrugated anionic layers.
AB  - The ternary pnictides Rb4Zn7As7 and Rb7Mn12Sb12 and their quaternary derivatives
      Rb4Mn3.5Zn3.5Sb7 and Rb7Mn4Cd8Sb12 have been prepared by reactions of the
      elements at 600  degrees C. They crystallize in two new structure types:
      orthorhombic Rb4Zn7As7-type (space group Cmcm, Z = 4; a = 4.1883(4) A, b =
      24.844(2) A, c = 17.6056(17) A for Rb4Zn7As7; a = 4.3911(8) A, b = 26.546(5) A, c
      = 18.743(4) A for Rb4Mn3.5Zn3.5Sb7) and monoclinic Rb7Mn12Sb12-type (space group
      C2/m, Z = 2; a = 26.544(12) A, b = 4.448(2) A, c = 16.676(8) A, beta = 103.183(8)
      degrees  for Rb7Mn12Sb12; a = 27.009(4) A, b = 4.5752(7) A, c = 16.727(3) A, beta
      = 103.221(2) degrees  for Rb7Mn4Cd8Sb12). These related structures contain
      corrugated anionic layers built up by connecting ribbons of edge-sharing
      tetrahedra in a zigzag-like manner with chains of Mn-centered square pyramids
      located at the hinges. Homoatomic pnicogen-pnicogen bonding occurs in the form of
      Pn2 pairs. The compounds are formally deficient by one electron per formula unit,
      as confirmed by band structure calculations which reveal the location of the
      Fermi level just below a small gap in Rb4Zn7As7 or a pseudogap in Rb7Mn12Sb12. 

PMID- 24116990
TI  - Journal of Women & Aging. From the editor.

PMID- 24116992
TI  - Anxiety, depression and alexithymia in fibromyalgia: are there any differences
      according to age?
AB  - This article analyzes the evolution of alexithymia, anxiety, and depression
      associated with fibromyalgia (FM) in three age groups in comparison to how they
      evolve in the same age groups in healthy women. A total of 240 women participated
      in the study (120 diagnosed with fibromyalgia and 120 healthy women), divided
      into three age groups (<=35 years,>35 and <65 years, and >=65 years old). Our
      analysis revealed that alexithymia, anxiety, and depression in FM patients showed
      increased levels compared to healthy controls. Also, young women with FM (under
      35) show lower alexithymia, anxiety, and depression levels in comparison to older
      patients (>=65). Alexithymia in FM patients follows a similar pattern as in
      healthy women (although with significantly higher scores), increasing with age.
      Our results show that depression, anxiety, and alexithymia develop over age in a
      different way in FM patients than in healthy individuals, increasing over age. 

PMID- 24116991
TI  - Characteristics of women with body size satisfaction at midlife: results of the
      Gender and Body Image (GABI) Study.
AB  - This study characterizes the profile of women (N = 1,789) ages 50 and over who
      report body size satisfaction on a figure rating scale. Satisfied women (12.2%)
      had a lower body mass index and reported fewer eating disorder symptoms, dieting
      behaviors, and weight and appearance dissatisfaction. Interestingly, satisfied
      women exercised more than dissatisfied women, and weight and shape still played a
      primary role in their self-evaluation. Weight monitoring and appearance-altering
      behaviors did not differ between groups. Body satisfaction was associated with
      better overall functioning. This end point appears to represent effortful body
      satisfaction rather than passive contentment.

PMID- 24116993
TI  - Women's receipt of Social Security retirement benefits: expectations compared to
      elections.
AB  - This research contributes knowledge regarding the options of early, normal, or
      delayed receipt of Social Security retirement benefits and research-based
      findings regarding women's expected and actual timing of election of Social
      Security retirement benefits. First, descriptive analyses of alternative
      retirement options, based on Social Security retirement benefit rules, are
      provided. Second, the 2000, 2002, 2004, and 2006 waves of Health and Retirement
      Study (HRS) data are used to analyze women's anticipated and actual election of
      Social Security retirement benefits. Third, based on these considerations,
      recommendations are made regarding Social Security retirement benefit receipt
      alternatives. 

PMID- 24116994
TI  - Formerly homeless, older women's experiences with health, housing, and aging.
AB  - The perspectives of formerly homeless, older women are absent in the academic
      literature on aging and homelessness. In this study, a group of formerly homeless
      women, aged 45 years and older were surveyed (N = 15) and interviewed (n = 11)
      about their experiences with health, housing, and aging. The qualitative themes
      to be explored include the women's perceptions of their current health, coping
      with low incomes, dealing with addictions to alcohol and drugs, and the
      importance of supportive housing and other community services. The female
      participants' views on adapting to home, planning for their elderly years, and
      views on growing older are also explored. 

PMID- 24116995
TI  - Intimate partner violence in older women in Spain: prevalence, health
      consequences, and service utilization.
AB  - The purpose of this study is to estimate the prevalence of lifetime intimate
      partner violence (IPV) in older women and to analyze its effect on women's health
      and Healthcare Services utilization. Women aged 55 years and over (1,676)
      randomly sampled from Primary Healthcare Services around Spain were included.
      Lifetime IPV prevalence, types, and duration were calculated. Descriptive and
      multivariate procedures using logistic and multiple lineal regression models were
      used. Of the women studied, 29.4% experienced IPV with an average duration of 21
      years. Regardless of the type of IPV experienced, abused women showed
      significantly poorer health and higher healthcare services utilization compared
      to women who had never been abused. The high prevalence detected long standing
      duration, negative health impact, and high healthcare services utilization,
      calling attention to a need for increased efforts aimed at addressing IPV in
      older women. 

PMID- 24116999
TI  - CD3zeta-based chimeric antigen receptors mediate T cell activation via cis- and
      trans-signalling mechanisms: implications for optimization of receptor structure
      for adoptive cell therapy.
AB  - Chimeric antigen receptors (CARs) can mediate redirected lysis of tumour cells in
      a major histocompatibility complex (MHC)-independent manner, thereby enabling
      autologous adoptive T cell therapy for a variety of malignant neoplasms.
      Currently, most CARs incorporate the T cell receptor (TCR) CD3zeta signalling
      chain; however, the precise mechanisms responsible for CAR-mediated T cell
      activation are unclear. In this study, we used a series of immunoreceptor
      tyrosine-based activation motif (ITAM)-mutant and transmembrane-modified
      receptors to demonstrate that CARs activate T cells both directly via the antigen
      ligated signalling chain and indirectly via associated chains within the TCR
      complex. These observations allowed us to generate new receptors capable of
      eliciting polyfunctional responses in primary human T cells. This work increases
      our understanding of CAR function and identifies new avenues for the optimization
      of CAR-based therapeutic interventions. 

PMID- 24117000
TI  - Improved adequacy of prenatal care and healthcare utilization among low-income
      Latinas receiving group prenatal care.
AB  - BACKGROUND: This study aimed to examine the effectiveness of the
      CenteringPregnancy group prenatal care model in improving maternal and child
      health outcomes, satisfaction with prenatal care, and engagement in prenatal
      care. METHODS: Pregnant Hispanic women <=20 weeks gestation initiating prenatal
      care at two Palm Beach County, Florida, public health clinics selected
      CenteringPregnancy or traditional prenatal care. Data on postpartum visit
      compliance, establishment of a medical home, child emergency room visits,
      satisfaction with prenatal care, and engagement in prenatal care were obtained
      through surveys conducted 3 months post-delivery (n=176; 129 CenteringPregnancy,
      47 traditional). Data on prenatal care visits were obtained through abstraction
      of Palm Beach County Health Department medical records (n=214; 144
      CenteringPregnancy, 70 traditional). RESULTS: Statistically significant
      differences were found in satisfaction with prenatal care (84.3 Centering vs.
      64.9 traditional, p<.001) and engagement in (39.7 vs. 28.1, p<.001). Centering
      participants had higher expected prenatal care ratios than traditional care
      participants (101.9 vs. 83.1, p<.001) and higher percentages receiving adequate
      prenatal care (90% vs. 63%, p<.001). Centering recipients were more likely to
      establish a medical home for their child (77% vs. 53%, p<.01) and have a
      postpartum checkup within six weeks of delivery (99% vs. 94%, p=.04).
      CONCLUSIONS: CenteringPregnancy improves engagement in prenatal care and
      healthcare utilization outcomes for low-income Latinas. Given disparities that
      exist between perinatal Latinas and women from other racial/ethnic groups,
      CenteringPregnancy should be considered as an alternative to traditional 1-on-1
      prenatal care for this population.

PMID- 24117001
TI  - Physical activity and musculoskeletal injuries in women: the Women's Injury
      Study.
AB  - BACKGROUND: Increased injury rates have been associated with physical activity
      (PA). The differences in musculoskeletal injury (MSI) characteristics resulting
      from PA, versus those unrelated to PA, are unknown. We describe the pattern of PA
      and non-PA MSI incurred by community-dwelling women. METHODS: Data were extracted
      from the Women's Injury Study, a web-based observational study that tracked
      weekly PA behaviors and self-reported MSI of 909 community-dwelling women ages 20
      83 years. The primary outcome was self-reported MSI that interrupted daily
      activities >=2 days and/or required treatment from a health care provider. Follow
      up telephone reporting of MSIs allowed further description of injuries. Mixed
      effects logistic regression was used to identify injury sites associated with PA,
      controlling for age, body mass index, previous injury, and use of alcohol.
      RESULTS: Incidence of PA and non-PA MSIs were comparable; some differences in
      injury characteristics were evident across 83,241 person-weeks of reporting. Non
      PA MSIs were more likely to come on "suddenly" (54% vs. 8%) and commonly involved
      head/jaw/neck injuries. Reported PA-related MSIs were less likely to require
      health care provider treatment (60% vs. 80%) and resulted in less missed days of
      work/school (11%) versus non-PA MSIs (17%). Compared to non-PA related injuries,
      PA-related injuries were more likely to involve the lower (odds ratio [OR]=3.10,
      p=0.002) or upper limbs (OR=2.54, p=0.01) and less likely to involve the
      head/jaw/neck (OR=0.21, p=0.002). CONCLUSION: There are some differences in
      mechanisms of injury, the distribution of injuries by anatomical location, and
      the treatment of injuries depending on aerobic activity participation, although
      absolute rates of MSI were comparable.

PMID- 24117002
TI  - Apparent insufficiency of iodine supplementation in pregnancy.
AB  - BACKGROUND: Pregnant woman are at increased risk for iodine deficiency, which may
      induce thyroid insufficiency and have damaging effects not only on the mother but
      also the fetus. We hypothesize that iodine supplementation during pregnancy
      reduces the risk for iodine deficiency. METHODS: Cross-sectional study to assess
      iodine levels in random urine specimens during pregnancy in New York City. One
      hundred eighty-two women visited a clinic where free iodine supplementation was
      offered (150 MUg of potassium iodide daily; Group A), and 183 women were seen at
      a practice at which no supplementation was offered (Group B). RESULTS: Overall,
      more than one out of two pregnant women in New York City were at risk for iodine
      deficiency with a spot urinary iodine (UI) level less than 150 MUg/L and could be
      defined as at risk for iodine deficiency. The median urine iodine concentration
      for the entire group was 152.5 MUg/L, but there was considerable variation from
      10.9 to 1210 MUg/L. The median UI level of the supplemented Group A (169.8 MUg/L)
      was significantly greater than that of Group B (128.4 MUg/L; p<0.01). Based on
      World Health Organization (WHO) guidelines, 38.9% of Group B women were at risk
      for mild, moderate, or severe iodine deficiency, compared with 22.8% of Group A
      women. CONCLUSIONS: New York City pregnant women were significantly less prone to
      iodine deficiency when provided with iodine supplementation. Nevertheless, when
      spot UI levels were used to estimate iodine sufficiency, more than 20% of
      supplemented women were still at risk for iodine deficiency according to WHO
      guidelines, suggesting that current supplementation practices remain
      insufficient.

PMID- 24117004
TI  - Pathophysiology of medication overuse headache--an update.
AB  - The pathogenesis of medication overuse headache is unclear. Clinical and
      preclinical studies have consistently demonstrated increased excitability of
      neurons in the cerebral cortex and trigeminal system after medication overuse.
      Cortical hyperexcitability may facilitate the development of cortical spreading
      depression, while increased excitability of trigeminal neurons may facilitate the
      process of peripheral and central sensitization. These changes may be secondary
      to the derangement of central, probably serotonin (5-HT)-, and perhaps
      endocannabinoid-dependent or other, modulating systems. Increased expression of
      excitatory cortical 5-HT2A receptors may increase the susceptibility to
      developing cortical spreading depression, an analog of migraine aura. A reduction
      of diffuse noxious inhibitory controls may facilitate the process of central
      sensitization, activate the nociceptive facilitating system, or promote similar
      molecular mechanisms to those involved in kindling. Low 5-HT levels also increase
      the expression and release of calcitonin gene-related peptide from the trigeminal
      ganglion and sensitize trigeminal nociceptors. Thus, derangement of central
      modulation of the trigeminal system as a result of chronic medication use may
      increase sensitivity to pain perception and foster or reinforce medication
      overuse headache. 

PMID- 24117003
TI  - Prevalence of sleep deficiency in early gestation and its associations with
      stress and depressive symptoms.
AB  - OBJECTIVE: Sleep deficiency is an emerging concept denoting a deficit in the
      quantity or quality of sleep. This may be particularly salient for pregnant women
      since they report considerable sleep complaints. Sleep deficiency is linked with
      morbidity, including degradations in psychosocial functioning, (e.g., depression
      and stress), which are recognized risk factors for adverse pregnancy outcomes. We
      sought to describe the frequency of sleep deficiency across early gestation (10
      20 weeks) and whether sleep deficiency is associated with reports of more
      depressive symptoms and stress. METHODS: Pregnant women (N=160) with no self
      reported sleep or psychological disorder provided sleep data collected via diary
      and actigraphy during early pregnancy: 10-12, 14-16, and 18-20 weeks' gestation.
      Sleep deficiency was defined as short sleep duration, insufficient sleep, or
      insomnia. Symptoms of depression and stress were collected at the same three time
      points. Linear mixed effects models were used to analyze the data. RESULTS:
      Approximately 28%-38% met criteria for sleep deficiency for at least one time
      point in early gestation. Women who were sleep deficient across all time points
      reported more perceived stress than those who were not sleep deficient (p<0.01).
      Depressive symptoms were higher among women with diary-defined sleep deficiency
      across all time points (p=0.02). DISCUSSION: Sleep deficiency is a useful concept
      to describe sleep recognized to be disturbed in pregnancy. Women with persistent
      sleep deficiency appear to be at greater risk for impairments in psychosocial
      functioning during early gestation. These associations are important since
      psychosocial functioning is a recognized correlate of adverse pregnancy outcomes.
      Sleep deficiency may be another important risk factor for adverse pregnancy
      outcomes.

PMID- 24117005
TI  - TRAIL receptor deficiency sensitizes mice to dextran sodium sulphate-induced
      colitis and colitis-associated carcinogenesis.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor
      (TRAIL-R) play important roles in immune regulation and cancer cell death.
      Although TRAIL has been shown to induce chemokine release in various tumour
      cells, the function of TRAIL-R in the development of colitis and colitis
      associated carcinogenesis has not been explored. In this study, we found that
      TRAIL-R-deficient mice exhibited a higher incidence of colitis and colitis
      associated cancer than that of wild-type (WT) mice, and TRAIL-R expression was
      down-regulated in WT mice that were fed dextran sulphate sodium. Chemokines,
      including CCL2 and CXCL1, were highly expressed in the serum and inflammatory
      colon tissues of TRAIL-R(-/-) mice compared with WT mice, and TRAIL-R(-/-) mice
      showed a marked infiltration of immune cells during colitis. Hyperactivation of
      Janus kinase and nuclear factor-kappaB in colon epithelial cells was also
      observed, which correlated with the severity of colonic inflammation in TRAIL-R(
      /-) mice. These data suggest that TRAIL-R plays a protective role in chemical
      induced colon injury and negatively regulates mucosal immune responses. 

PMID- 24117006
TI  - Evaluation of focus laterality in temporal lobe epilepsy: a quantitative study
      comparing double inversion-recovery MR imaging at 3T with FDG-PET.
AB  - PURPOSE: To quantitatively compare the diagnostic capability of double inversion
      recovery (DIR) with F-18 fluorodeoxyglucose positron emission tomography (FDG
      PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE).
      METHODS: This study was approved by the institutional review board, and written
      informed consent was obtained. Fifteen patients with TLE and 38 healthy
      volunteers were enrolled. All magnetic resonance (MR) images were acquired using
      a 3T-MRI system. Voxel-based analysis (VBA) was conducted for FDG-PET images and
      white matter segments of DIR images (DIR-WM) focused on the whole temporal lobe
      (TL) and the anterior part of the temporal lobe (ATL). Distribution of
      hypometabolic areas on FDG-PET and increased signal intensity areas on DIR-WM
      were evaluated, and their laterality was compared with clinically determined
      seizure focus laterality. Correct diagnostic rates of laterality were evaluated,
      and agreement between DIR-WM and FDG-PET was assessed using kappa statistics. KEY
      FINDINGS: Increased signal intensity areas on DIR-WM were located at the vicinity
      of the hypometabolic areas on FDG-PET, especially in the ATL. Correct diagnostic
      rates of seizure focus laterality for DIR-WM (0.80 and 0.67 for the TL and the
      ATL, respectively) were slightly higher than those for FDG-PET (0.67 and 0.60 for
      the TL and the ATL, respectively). Agreement of laterality between DIR-WM and FDG
      PET was substantial for the TL and almost perfect for the ATL (kappa = 0.67 and
      0.86, respectively). SIGNIFICANCE: High agreement in localization between DIR-WM
      and FDG-PET and nearly equivalent detectability of them show us an additional
      role of MRI in TLE.

PMID- 24117007
TI  - Normal prion protein is expressed on exosomes isolated from human plasma.

PMID- 24117008
TI  - Melatonin MT1 and MT2 receptors display different molecular pharmacologies only
      in the G-protein coupled state.
AB  - BACKGROUND AND PURPOSE: Melatonin receptors have been extensively characterized
      regarding their affinity and pharmacology, mostly using 2-[(125)I]-melatonin as a
      radioligand. Although [(3)H]-melatonin has the advantage of corresponding to the
      endogenous ligand of the receptor, its binding has not been well described.
      EXPERIMENTAL APPROACH: We characterized [(3)H]-melatonin binding to the hMT1 and
      hMT2 receptors expressed in a range of cell lines and obtained new insights into
      the molecular pharmacology of melatonin receptors. KEY RESULTS: The binding of
      [(3)H]-melatonin to the hMT1 and hMT2 receptors displayed two sites on the
      saturation curves. These two binding sites were observed on cell membranes
      expressing recombinant receptors from various species as well as on whole cells.
      Furthermore, our GTPgammaS/NaCl results suggest that these sites on the
      saturation curves correspond to the G-protein coupled and uncoupled states of the
      receptors, whose pharmacology was extensively characterized. CONCLUSIONS AND
      IMPLICATIONS: hMT1 and hMT2 receptors spontaneously exist in two states when
      expressed in cell lines; these states can be probed by [(3)H]-melatonin binding.
      Overall, our results suggest that physiological regulation of the melatonin
      receptors may result from complex and subtle mechanisms, a small difference in
      affinity between the active and inactive states of the receptor, and spontaneous
      coupling to G-proteins.

PMID- 24117009
TI  - Aminoacylase I deficiency due to ACY1 mRNA exon skipping.
AB  - Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism of which
      less than 20 observations have been described. Patients exhibit urinary excretion
      of specific N-acetyl amino acids and manifest a heterogeneous clinical spectrum
      including intellectual disability, motor delay, seizures, moderate to severe
      mental retardation, absent speech, growth delay, muscular hypotonia and autistic
      features. Here, we report the case of ACY1 enzyme deficiency in a 6-year-old girl
      presenting severe intellectual disability, motor retardation, absence of
      spontaneous locomotor activity and severe speech delay. Urinary excretion of N
      acetylated amino acids was present. Mutational analysis of ACY1 gene identified
      the new homozygous c.1001_1001+5del6 mutation, which alters the mRNA
      transcription leading to exon 13 skipping and inclusion of a premature stop codon
      (p.Lys308Glufs*7). A quantitative fluorescent multiplex-polymerase chain reaction
      (QFM-PCR) assay has been set up and confirmed homozygosity of the mutation in the
      patient's DNA. Biochemical analysis showed absence of ACY1 enzyme activity in the
      patient's fibroblasts. The structure of the mutated protein has been defined by
      homology modeling (HM). Our data endorse the hypothesis of a link between this
      inborn error of metabolism and the neurological manifestations observed in
      patients with ACY1 deficiency. 

PMID- 24117010
TI  - (-)-Cytisine and derivatives: synthesis, reactivity, and applications.

PMID- 24117012
TI  - Factorial validity of the Personality Adjective Checklist in a Dutch-speaking
      sample.
AB  - We examined the factorial structure of the Dutch version of the Personality
      Adjective Checklist (PACL-D) in a Belgian sample of 3,012 community-dwelling
      adults. Exploratory factor analyses revealed a 5-factor structure (Neurotic,
      Aggressive/Dominant, Introverted vs. Extraverted, Conscientious, and
      Cooperative), that showed considerable overlap with 3 of the Big Five factors
      (i.e., Neuroticism, Extraversion, and Conscientiousness). Moreover, the 5-factor
      structure closely resembled the structure found in the original American PACL and
      was equivalent across gender and age. 

PMID- 24117011
TI  - Hyperglycaemia increases S100beta after short experimental cardiac arrest.
AB  - BACKGROUND: Hyperglycaemia is associated with aggravated ischaemic brain injury.
      The main objective of this study was to investigate the effects on cerebral
      perfusion of 5 min of cardiac arrest during hyperglycaemia and normoglycaemia.
      METHODS: Twenty triple-breed pigs (weight: 22-29 kg) were randomised and clamped
      at blood glucose levels of 8.5-10 mM [high (H)] or 4-5.5 mM [normal (N)] and
      thereafter subjected to alternating current-induced 5 min-cardiac arrest followed
      by 8 min of cardiopulmonary resuscitation and direct current shock to restore
      spontaneous circulation. RESULTS: Haemodynamics, laser Doppler measurements and
      regional venous oxygen saturation (HbO2) were monitored, and biochemical markers
      in blood [S100beta, interleukin (IL)-6 and tumour necrosis factor (TNF)]
      quantified throughout an observation period of 3 h. The haemodynamics and
      physiological measurements were similar in the two groups. S100beta increased
      over the experiment in the H compared with the N group (P < 0.05). IL-6 and TNF
      levels increased across the experiment, but no differences were seen between the
      groups. CONCLUSIONS: The enhanced S100beta response is compatible with increased
      cerebral injury by hyperglycaemic compared with normoglycaemic 5 min of cardiac
      arrest and resuscitation. The inflammatory cytokines were similar between groups.

PMID- 24117014
TI  - Tzanck smear utilized in the diagnosis of Hailey-Hailey disease mimicking genital
      herpes.

PMID- 24117013
TI  - A combination microbicide gel protects macaques against vaginal simian human
      immunodeficiency virus-reverse transcriptase infection, but only partially
      reduces herpes simplex virus-2 infection after a single high-dose cochallenge.
AB  - Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We
      previously established a rhesus macaque model of vaginal HSV-2 preexposure
      followed by cochallenge with HSV-2 and simian/human immunodeficiency virus
      reverse transcriptase (SHIV-RT). Using this model, we showed that a gel
      containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in
      carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new
      generation microbicides against both viruses, we first established dual infection
      after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques.
      All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a
      control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV
      RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and
      T cell responses were detected in some HSV-2-infected animals. To test a CG gel
      containing MIV-150 and zinc acetate (MZC), which provided naive animals full
      protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14
      days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9
      infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20%
      (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel
      treated animals seroconverted, and only the CG controls had measurable HSV-2
      specific T cell responses. This study shows the promise of MZC to prevent
      immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2
      infection after exposure to a high-dose inoculum. Additionally, it demonstrates
      the potential of a macaque coinfection model to evaluate broad-spectrum
      microbicides.

PMID- 24117015
TI  - Efficient search of chemical space: navigating from fragments to structurally
      diverse chemotypes.
AB  - We introduce a novel strategy to sample bioactive chemical space, which follows
      up on hits from fragment campaigns without the need for a crystal structure. Our
      results strongly suggest that screening a few hundred or thousand fragments can
      substantially improve the selection of small-molecule screening subsets. By
      combining fragment-based screening with virtual fragment linking and HTS
      fingerprints, we have developed an effective strategy not only to expand from low
      affinity hits to potent compounds but also to hop in chemical space to
      substantially novel chemotypes. In benchmark calculations, our approach accessed
      subsets of compounds that were substantially enriched in chemically diverse hit
      compounds for various activity classes. Overall, half of the hits in the
      screening collection were found by screening only 10% of the library.
      Furthermore, a prospective application led to the discovery of two structurally
      novel histone deacetylase 4 inhibitors. 

PMID- 24117016
TI  - The expression and function of histamine H3 receptors in pancreatic beta cells.
AB  - BACKGROUND AND PURPOSE: Histamine and its receptors in the CNS play important
      roles in energy homeostasis. Here, we have investigated the expression and role
      of histamine receptors in pancreatic beta cells, which secrete insulin.
      EXPERIMENTAL APPROACH: The expression of histamine receptors in pancreatic beta
      cells was examined by RT-PCR, Western blotting and immunostaining. Insulin
      secretion assay, ATP measurement and calcium imaging studies were performed to
      determine the function and signalling pathway of histamine H3 receptors in
      glucose-induced insulin secretion (GIIS) from MIN6 cells, a mouse pancreatic beta
      cell line. The function and signalling pathway of H3 receptors in MIN6 cell
      proliferation were examined using pharmacological assay and Western blotting. KEY
      RESULTS: Histamine H3 receptors were expressed in pancreatic beta cells. A
      selective H3 receptor agonist, imetit, and a selective inverse H3 receptor
      agonist, JNJ-5207852, had inhibitory and facilitatory effects, respectively, on
      GIIS in MIN6 cells. Neither imetit nor JNJ-5207852 altered intracellular ATP
      concentration, or intracellular calcium concentration stimulated by glucose and
      KCl, indicating that GIIS signalling was affected by H3 receptor signalling
      downstream of the increase in intracellular calcium concentration. Moreover,
      imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The
      phosphorylation of cAMP response element-binding protein (CREB), which
      facilitated beta cell proliferation, was inhibited, though not significantly, by
      imetit, indicating that activated H3 receptors inhibited MIN6 cell proliferation,
      possibly by decreasing CREB phosphorylation. CONCLUSIONS AND IMPLICATIONS:
      Histamine H3 receptors were expressed in mouse beta cells and could play a role
      in insulin secretion and, possibly, beta cell proliferation.

PMID- 24117018
TI  - Risk of cerebral palsy in term-born singletons according to growth status at
      birth.
AB  - AIMS: An excess risk of cerebral palsy (CP) has been reported in children of both
      low and high birthweight. However, the risk associated with deviations from the
      mean of other anthropometric measurements has been less well studied. The aim of
      our study therefore was to determine the association between size measurements at
      birth and incidence of CP in singletons born at term. METHOD: Standard deviation
      z-scores for weight, length, head circumference, and ponderal index at birth of
      term-born singletons born between 1996 and 2006 were calculated using data from
      the Medical Birth Registry of Norway. The measurements of 398 children with CP
      recorded in the Cerebral Palsy Registry of Norway were compared with those of
      490,022 typically developing infants. RESULTS: Children with low birthweight
      (p<0.001; <10th centile) as well as low and high z-scores for length (p<0.001 and
      p<0.001) and head circumference (p<0.001 and p<0.003; <90th centile) had an
      excess risk of CP, in particular of spastic bilateral CP. Spastic unilateral CP
      was associated only with low z-scores, whereas children with the greatest body
      length and largest head circumference, but with low ponderal index, had an excess
      risk of spastic quadriplegic and dyskinetic CP. INTERPRETATION: Our results are
      consistent with the notion that most subtypes of CP are due to antenatal factors
      leading to poor intrauterine growth, whereas CP in children who were large at
      birth is more likely to be due to intrapartum factors.

PMID- 24117017
TI  - Hypoxia promotes CEMP1 expression and induces cementoblastic differentiation of
      human dental stem cells in an HIF-1-dependent manner.
AB  - Cementum covering the tooth root provides attachment for the tooth proper to the
      surrounding alveolar bone via non-mineralized periodontal ligament (PDL).
      Cementum protein 1 (CEMP1) has been shown to induce a cementoblastic phenotype in
      cementoblast precursors cells of PDL. Oxygen availability is a critical signal
      for correct development of many tissues; however, its role in tooth root and
      periodontium development remains poorly understood. In this study, we
      demonstrated that reduced oxygen tension increased CEMP1 expression, mineral
      deposition, and alkaline phosphatase activity in human dental stem cells such as
      PDL stem cells and periapical follicular stem cells. Since an oxemic state is
      transduced by the transcription factor, hypoxia-inducible factor-1 (HIF-1), we
      performed experiments to determine whether this protein was responsible for the
      observed changes. We noted that when HIF-1 was activated by gene introduction or
      chemically, CEMP1 expression and mineralization increased. In contrast, when HIF
      1alpha was silenced, CEMP1 expression and mineralization did not increase in
      vitro. Furthermore, we showed for the first time that mouse tooth root and
      periodontium development occurs partly under hypoxic conditions, particularly at
      the apical part and latently at the PDL space in vivo. Desferrioxamine, an HIF-1
      stimulator, enhances CEMP1 expression in the mouse PDL space, suggesting that
      hypoxia affects cementogenesis of PDL cells lining the surface of the developing
      tooth root in an HIF-1-dependent manner. These results suggest that HIF-1
      activators may have the ability to stimulate regeneration of the tooth root and
      cementum formation. 

PMID- 24117023
TI  - Determinants of drug survival for etanercept in a long-term daily practice cohort
      of patients with psoriasis.
AB  - BACKGROUND: Long-term data of etanercept drug survival in patients with psoriasis
      in daily practice are scarce. OBJECTIVES: The primary objective was to describe
      drug survival for etanercept in a long-term daily practice cohort of patients
      with psoriasis. The secondary objective was to identify determinants of drug
      survival for etanercept in general and separately for discontinuation due to
      adverse events or ineffectiveness of therapy. METHODS: Data were extracted from a
      prospective daily practice cohort of patients treated with biologics for
      psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split
      for two reasons for discontinuation: adverse events and ineffectiveness.
      Determinants of drug survival were analysed using univariate Cox regression
      analysis and multivariate Cox regression analysis with backward selection.
      RESULTS: We included 193 patients (512 patient-years treated) with a maximum
      treatment duration of 7.5 years. The overall drug survival rates were 77%, 41%
      and 30% after 1, 4 and 7.5 years, respectively. The mean survival duration was
      3.8 years (95% confidence interval 3.4-4.3). Reasons for discontinuation were
      ineffectiveness (33.7%), adverse events (11.9%), both ineffectiveness and adverse
      events (4.7%) or other reasons (e.g. pregnancy planned) (5.7%). Determinants
      related to longer general drug survival were male sex [hazard ratio (HR) 0.55],
      prior anti-tumour necrosis factor (TNF)-alpha use (HR 0.57) and lower etanercept
      dose (HR 0.65). Younger age (HR 0.83), lower body mass index (HR 0.63) and lower
      etanercept dose (HR 0.71) were related to a decreased risk of discontinuation due
      to side-effects. A lower mean weekly dose of etanercept (HR 0.63) was related to
      a decreased risk of discontinuation due to ineffectiveness of therapy.
      CONCLUSIONS: We present the longest analysis of drug survival for etanercept in
      psoriasis to date. Determinants of longer overall etanercept drug survival were
      male sex, prior anti-TNF therapy and lower etanercept dose. The determinants of
      longer drug survival depended on the reason for discontinuation of etanercept.

PMID- 24117024
TI  - Optical properties of single infrared resonant circular microcavities for surface
      phonon polaritons.
AB  - Plasmonic antennas are crucial components for nano-optics and have been
      extensively used to enhance sensing, spectroscopy, light emission,
      photodetection, and others. Recently, there is a trend to search for new
      plasmonic materials with low intrinsic loss at new plasmon frequencies. As an
      alternative to metals, polar crystals have a negative real part of permittivity
      in the Reststrahlen band and support surface phonon polaritons (SPhPs) with weak
      damping. Here, we experimentally demonstrate the resonance of single circular
      microcavities in a thin gold film deposited on a silicon carbide (SiC) substrate
      in the mid-infrared range. Specifically, the negative permittivity of SiC leads
      to a well-defined, size-tunable SPhP resonance with a Q factor of around 60 which
      is much higher than those in surface plasmon polariton (SPP) resonators with
      similar structures. These infrared resonant microcavities provide new
      possibilities for widespread applications such as enhanced spectroscopy, sensing,
      coherent thermal emission, and infrared photodetectors among others throughout
      the infrared frequency range. 

PMID- 24117025
TI  - Single walled carbon nanotube-metal oxide nanocomposites for reversible and
      reproducible storage of hydrogen.
AB  - Composite material consisting of single walled carbon nanotubes (SWCNTs) and
      metal oxide nanoparticles has been prepared and their hydrogen storage
      performance is evaluated. Metal oxides such as tin oxide (SnO2), tungsten
      trioxide (WO3), and titanium dioxide (TiO2) are chosen as the composite
      constituents. The composites have been prepared by means of ultrasonication.
      Then, the composite samples are deposited on alumina substrates and at 100 
      degrees C in a Sieverts-like hydrogenation setup. Characterization techniques
      such as transmission electron microscopy (TEM), Raman spectroscopy, scanning
      electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier transform
      infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), CHN elemental
      analysis, and thermogravimetric (TG) measurements are used to analyze the samples
      at various stages of experiments. Hydrogen storage capacity of the composites
      namely, SWCNT-SnO2, SWCNT-WO3, and SWCNT-TiO2 are found to be 1.1, 0.9, and 1.3
      wt %, respectively. Hydrogenated composite samples are stable at room temperature
      and desorption of hydrogen is found to be 100% reversible. Desorption temperature
      ranges and binding energy ranges of hydrogen have been measured from the
      desorption studies. The hydrogenation, dehydrogenation temperature, and binding
      energy of hydrogen fall in the recommended range of a suitable hydrogen storage
      medium applicable for fuel cell applications. Reproducibility and deterioration
      level of the composite samples have also been examined. 

PMID- 24117027
TI  - Modeling individual specific fish length from capture-recapture data using the
      von Bertalanffy growth curve.
AB  - We use Bayesian methods to explore fitting the von Bertalanffy length model to
      tag-recapture data. We consider two popular parameterizations of the von
      Bertalanffy model. The first models the data relative to age at first capture;
      the second models in terms of length at first capture. Using data from a rainbow
      trout Oncorhynchus mykiss study we explore the relationship between the
      assumptions and resulting inference using posterior predictive checking, cross
      validation and a simulation study. We find that untestable hierarchical
      assumptions placed on the nuisance parameters in each model can influence the
      resulting inference about parameters of interest. Researchers should carefully
      consider these assumptions when modeling growth from tag-recapture data. 

PMID- 24117026
TI  - Myasthenia gravis: an update for the clinician.
AB  - This paper provides a thorough overview of the current advances in diagnosis and
      therapy of myasthenia gravis (MG). Nowadays the term 'myasthenia gravis' includes
      heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular
      transmission as the common feature. Myasthenia gravis should be classified
      according to the antibody specificity [acetylcholine, muscle-specific receptor
      tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4
      (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at
      onset (in children; aged less than or more than 50 years) and type of course
      (ocular or generalized). With optimal treatment, the prognosis is good in terms
      of daily functions, quality of life and survival. Symptomatic treatment with
      acetylcholine esterase inhibition is usually combined with immunosuppression.
      Azathioprine still remains the first choice for long-term immunosuppressive
      therapy. Alternative immunosuppressive options to azathioprine include
      cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and
      tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging
      therapy options include belimumab, eculizumab and the granulocyte- macrophage
      colony-stimulating factor. One pilot study on etanercept has given disappointing
      results. For decades, thymectomy has been performed in younger adults to improve
      non-paraneoplastic MG. However, controlled prospective studies on the suspected
      benefit of this surgical procedure are still lacking. In acute exacerbations,
      including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and
      immunoadsorption are similarly effective. 

PMID- 24117028
TI  - Magnetic polycarbonate microspheres for tumor-targeted delivery of tumor necrosis
      factor.
AB  - OBJECTIVE: The specific expression of transferrin receptor can represent a
      diagnostic tool or therapeutic target in solid tumors expressing this antigen.
      Herein, the human transferrin receptor monoclonal antibody (T9) was investigated
      as a tumor-targeting group for active targeted-drug delivery systems. MATERIALS
      AND METHODS: A tumor-targeted conjugate T9-TNF was synthesized by the attachment
      of both human transferrin receptor monoclonal antibody (T9) as a tumor-targeting
      group and human tumor necrosis factor-alpha (TNF) as an anti-cancer drug to two
      terminated hydroxyl groups of poly(ethylene glycol). Subsequently, a solvent
      evaporation technique was adopted to produce anti-cancer magnetic polymer
      microspheres T9-TNF-PC-M containing T9-TNF and Fe3O4 magnetic ultrafine powders
      (M) using poly(trimethylene carbonate-co-5,5-dimethyl trimethylene carbonate)
      (PC, P(TMC-co-DTC)) as a polymeric carrier. RESULTS AND DISCUSSION: These
      magnetic polycarbonate microspheres possessed a steady TNF release rate in
      phosphate buffer saline solution, strong magnetic responsiveness and high T9-TNF
      loading capacity. In vitro cytotoxicity assays demonstrated the microspheres T9
      TNF-PC-M and conjugate T9-TNF were strongly inhibitory to the human hepatic
      carcinoma (Bel-7204) cells. In vivo site-specific therapy in nude mice with human
      hepatic carcinoma indicated that the microspheres T9-TNF-PC-M and conjugate T9
      TNF possessed markedly higher anti-tumor activity against Bel-7204 in mice than
      that of TNF. CONCLUSIONS: These results indicated that the magnetic polycarbonate
      microspheres were suitable as the potential-targeted treatment for hepatic
      carcinoma therapeutics.

PMID- 24117029
TI  - Atypical alliances: the potential for social work and pharmacy collaborations in
      primary health care delivery.
AB  - The growing prevalence of chronic conditions is a cause for concern globally,
      both in terms of its impact on the health of populations and also the strain it
      is predicted to place on health resources. There is a push to adopt more holistic
      and collaborative approaches to health care, and for the education of health care
      professionals to be reformed if these efforts are to be successful. A research
      project was undertaken in New Zealand in 2010-2011 aimed at exploring the
      perceptions of health care professionals on competencies in the field of chronic
      care. This article aims to highlight learning from the project regarding the
      "atypical alliance" between social work and pharmacy. Based on this, the authors
      argue that, with the growing expectations for interprofessional collaboration,
      effective primary and community health care delivery is increasingly dependent on
      relationships between educators in different health disciplines, between health
      professionals-in-training, and between education providers and health
      organizations. 

PMID- 24117030
TI  - HIV case manager preparedness for practice in Ryan White CARE Act funded
      settings.
AB  - While current research on the factors affecting the HIV epidemic within the
      general population has considered the role of HIV case managers, much remains to
      be known about case management effectiveness and how it might be enhanced. This
      article presents the data from a statewide survey of case management
      professionals in Florida. The study focused on case managers' preparation for
      practice and barriers to successful practice. The study results reflect a very
      broad educational preparation in multiple disciplines with highly varied means of
      case manager training and orientation at entry to practice. Further, the results
      highlighted the existence of multiple barriers that challenge the ability of case
      managers to cope with the demands of case management practice in sites serving
      people living with HIV/AIDS who are socially and economically challenged. The
      article concludes with recommendations for changes in the system that would
      enhance the preparation of case management professionals for entry to practice. 

PMID- 24117031
TI  - Breaking through the silence: the experience of living with HIV-positive
      serostatus, and its implications on disclosure.
AB  - AIDS has reached pandemic proportions and despite advances in medical treatment
      both the medical and social consequences of HIV-positive serostatus continue to
      be of concern throughout the world. In countries with greater access to
      antiretroviral therapy (ARV), HIV/AIDS it is no longer defined as fatal, but
      rather a chronic disease, thereby this study seeks to understand the experience
      of individuals living with HIV-positive serostatus, a multifaceted disease, from
      the time the infection is diagnosed through the four post-diagnosis years, and in
      particular its implications on the issue of disclosure. A qualitative analysis
      was conducted, based on 13 in-depth interviews with participants who are HIV
      positive and the data was analyzed by inductive content analysis. The results
      identify six themes, four central elements that compose the experience of living
      with HIV: the emotional experience, the stigma attached to HIV, the inner
      dialogue, and disclosure. A three-phase coping process and personality
      differences were found, all of which will be discussed. The issue of disclosure
      was found to be cardinal and problematic in its impact on the patient's
      wellbeing. 

PMID- 24117032
TI  - Person-centeredness in home- and community-based long-term care: current
      challenges and new directions.
AB  - Person-centered care (PCC) has demonstrated to be a viable and preferred model of
      providing health and institutionalized long-term care services. However, the
      concept of PCC has not been fully extended to home- and community-based long-term
      care services (HCBS) for older adults with chronic conditions. This review
      highlights the need for PCC in HCBS and suggests that social workers may play a
      role in overcoming cultural and structural barriers to extending PCC to HCBS that
      include: the fragmentation of the industry, financial structures, regulation of
      services, and paternalism in policy and practice. Recommendations for practice,
      policy, and research are provided. 

PMID- 24117033
TI  - Examining preferences for website support to parents of adolescents with
      diabetes.
AB  - Diabetes can be stressful as parents seek optimal outcomes for their adolescent
      with type 1 diabetes. This study examined parents' interest and perspectives
      related to online diabetes resources. Based on a qualitative description
      approach, 14 qualitative group interviews were conducted with (i) parents of
      adolescents with diabetes (n = 29), and (ii) pediatric health care providers (n =
      31). Participants were recruited, through a purposive sampling approach, at
      pediatric centers in three Canadian cities. Qualitative data were subjected to
      thematic analysis comprising data coding, categorization, and ultimate theme
      generation. Participants described parental care for adolescents with diabetes as
      complex and reflective of difficult and nuanced tasks. They recommended the
      development of a comprehensive parent-based information and support website, and
      identified crucial elements of the website. Overarching themes comprised the
      following: complex parenting processes in diabetes care, parents' need for
      information and support, challenges and benefits of online support, key elements
      of an online resource, and caution regarding online resources. Based on these
      findings, website information and support emerged as a viable and desired
      resource for augmenting pediatric care within clinical settings. Caution was also
      offered in addressing potential challenges inherent in online support. Findings
      offer guidance for online support to parents.

PMID- 24117034
TI  - The psychological impact of breast and ovarian cancer preventive options in BRCA1
      and BRCA2 mutation carriers.
AB  - This study was performed to describe the impact of preventive options on the
      psychological condition of BRCA1/BRCA2 carriers. A sample of 52 cancer-affected
      (C-A) and 27 cancer-unaffected (C-UN) women were enrolled after gene test
      disclosure (T0). Psychological evaluations were performed at T0 and 15 months
      later (T1). The surgical options were more likely to be chosen in C-A women
      (62%), although a consistent proportion of C-UN women (30%) also opt for these
      preventive measures. At the baseline, both samples had average anxiety and
      depression scores below the cut-off value, restrained average cancer worry scores
      and a risk perception consistent with the risk percentage provided during genetic
      counselling. The longitudinal results indicated no clinically meaningful
      variations in the anxiety and depression scores in either of the two samples.
      Statistically significant reductions in cancer-risk perception emerged in women
      who chose surgery in both C-A and C-UN women. In BRCA1/BRCA2 mutation carriers,
      surveillance does not influence their initial psychological condition, whereas
      prophylactic surgery has a significant impact in reducing the perceived risk and
      worry about getting sick. C-A and C-UN women have to be considered as two
      separate populations of BRCA mutation carriers requiring personalized approaches
      to risk management.

PMID- 24117035
TI  - Ligation of the rectum with an extracorporeal sliding knot facilitating
      laparoscopic cross-stapling: a procedure revisited.
AB  - BACKGROUND: Multiple stapler firings during distal rectal division were
      associated with unduly long stapler line and anastomotic leakage after
      laparoscopic rectal resection. A simple and relatively easy technique to perform
      a safe transection of rectum is presented. MATERIALS AND METHODS: The
      extracorporeal ligation of the rectum just proximal to the cut end of the rectum
      before applying the linear stapling stapler facilitates the procedure and
      requires only a few firings of the stapler during the laparoscopic rectal
      resections. RESULTS: Ten patients with a median age of 72 years underwent rectal
      transection with this technique. The procedure was performed with a single 60-mm
      cartridge in 3 patients, and two firings of the Endo GIATM (Covidien LLC,
      Mansfield, MA) with a 45-mm cartridge were necessary for cross-stapling at the
      level of the pelvic floor in the remaining patients. There were no intraoperative
      complications. Postoperative complications were seen in 2 patients. CONCLUSIONS:
      This simple technique theoretically seems safer than the conventional approach
      and should be considered as an additional option for rectal transection.

PMID- 24117036
TI  - Single-incision laparoscopic colectomy using self-made glove port for benign
      colon diseases.
AB  - PURPOSE: The instrument crowding derived from commercially available access
      devices in single-incision laparoscopic surgery (SILS) is a challenge to
      overcome. This study was designed to evaluate the short-term surgical outcomes of
      SILS by applying a self-made device in patients with benign colon diseases.
      PATIENTS AND METHODS: We collected and reviewed the medical records of patients
      who received SILC by using a self-made glove-port system from March 2007 to July
      2012. All operations were performed by a single surgeon. Sixty-four patients (36
      males and 28 females) were enrolled for this study. Among them, 15 patients
      received right-side colon resection, 31 patients received left-side colon
      resection, and 18 patients received total colectomy. RESULTS: In the analysis of
      medical records from these groups of patients, we found that there was no
      significant difference of gender, body mass index, tumor size, incision length,
      and blood loss among these three groups. Furthermore, no significant difference
      of the pain scores, average length of hospital stay, and average duration of
      bowel return was observed among these three groups. However, it was notable that
      younger age, longer duration of operation, and longer bowel resection were indeed
      significantly found in the patients undergoing total colectomy. On the other
      hand, curved instruments were used in 5 (16.1%) of 31 patients with left-side
      colon resection. CONCLUSIONS: A simple self-made glove-port device was proven as
      a practical method of SILS for colorectal diseases. These findings suggested that
      single-incision laparoscopic total colectomy provides compatible clinical outcome
      in the patients with benign colon diseases compared with the other two surgical
      procedures used in this study.

PMID- 24117037
TI  - Evolution of an attenuated HIV-1 isolate in an elite suppressor.
AB  - Elite controllers or suppressors (ES) control viral replication without
      antiretroviral therapy. While many ES are infected with replication-competent
      virus, others have evidence of infection with attenuated isolates. Here we report
      a case of an ES infected with an HIV-1 isolate that contained a 38-base pair
      deletion in nef that led to a reading frame shift and a premature stop codon.
      Interestingly, clones amplified from plasma or cultured from CD4(+) T cells
      between 2006 and 2008 contained one of two separate compensatory deletions that
      restored the reading frame. A new insertion generated by duplication of adjacent
      sequences was found in isolates obtained in 2010 and this evolution was
      accompanied by the development of low level viremia. This article provides
      evidence of the evolution of an attenuated HIV-1 isolate toward greater virulence
      in an elite suppressor.

PMID- 24117039
TI  - Bloody tears, gardner-diamond syndrome, and trigemino-autonomic headache.

PMID- 24117040
TI  - An untold factor that may influence the rate of cesarean section.

PMID- 24117042
TI  - Clinical applicability and prognostic significance of molecular response assessed
      by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a
      GEM/PETHEMA study.
AB  - Minimal residual disease monitoring is becoming increasingly important in
      multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele
      specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not
      routinely available. This study investigated the prognostic influence of
      achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly
      diagnosed MM patients from Grupo Espanol Multidisciplinar de Melanoma
      (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved
      almost very good partial response after induction therapy. As a reference, we
      used the results observed with simultaneous MFC. F-PCR at diagnosis was performed
      on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE
      rearrangements. The applicability of F-PCR was 91.5%. After induction therapy, 64
      patients achieved molecular response and 66 non-molecular response; median
      progression-free survival (PFS) was 61 versus 36 months, respectively (P =
      0.001). Median overall survival (OS) was not reached (NR) in molecular response
      patients (5-year survival: 75%) versus 66 months in the non-molecular response
      group (P = 0.03). The corresponding PFS and OS values for patients with
      immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P
      = 0.005) and NR (5-year survival: 95%) versus 69 months (P = 0.004),
      respectively. F-PCR analysis is a rapid, affordable, and easily performable
      technique that, in some circumstances, may be a valid approach for minimal
      residual disease investigations in MM. 

PMID- 24117043
TI  - Significant involvement of nuclear factor-kappaB-inducing kinase in proper
      differentiation of alphabeta and gammadelta T cells.
AB  - Nuclear factor-kappaB-inducing kinase (NIK) is known to play a critical role in
      maintaining proper immune function. This is exemplified in the spontaneous mutant
      mouse lacking functional NIK, alymphoplasia (aly), which is simultaneously immune
      compromised and autoimmune-prone. To investigate the role of NIK in alphabeta T
      cell repertoire formation, we analysed T-cell development in aly/aly mice bearing
      a transgenic T-cell receptor (TCR). Although there were no apparent abnormalities
      in the mature alphabeta T cells of non-transgenic aly/aly mice, the maturation
      efficiency of idiotype(high+) T cells in the TCR-transgenic mice was lower in
      aly/aly mice compared with those found in aly/+ mice, suggesting that the mature
      alphabeta T-cell repertoire could be altered by the absence of functional NIK. In
      one strain of TCR-transgenic aly/aly mice with a negatively selecting H-2
      background, the proportion of CD8(low+) idiotype(high+) cells, which are thought
      to potentially represent the gammadelta lineage of T cells, was markedly
      decreased. When the gammadelta T cells in non-transgenic aly/aly mice were
      investigated, the proportion of gammadelta T cells in the peripheral organs of
      aly/aly mice was found to be one-half to one-fifth of those in aly/+ mice.
      Analyses of bone marrow chimera mice indicated that NIK in host cells, rather
      than in donor cells was important for generating a normal number of peripheral
      gammadelta T cells. Collectively, these results suggest that NIK could be
      involved in thymic positive selection of some alphabeta T cells and that NIK in
      non-haematopoietic cells is important for the optimal development and/or
      maintenance of gammadelta T cells.

PMID- 24117044
TI  - Differential effect of 14 free fatty acids in the expression of inflammation
      markers on human arterial coronary cells.
AB  - Cardiovascular disease is the leading cause of death in the United States, and
      circulating free fatty acids (FFAs) are known risk factors associated with
      cardiovascular inflammation. The influence of 14 dietary FFAs (including
      saturated, mono- and polyunsaturated, and trans) on the expression of
      inflammatory markers in human coronary arterial smooth muscle (HCASM) and
      endothelial (HCEC) cells using a cell culture model was investigated. HCASM and
      HCEC cell cultures were incubated with 200 MUM of each FFA for 8 or 24 h,
      respectively, at 37  degrees C in a 5% CO2 humidified incubator. Inflammatory
      markers were assessed by ELISA or Western blot in the supernatant or cell lysates
      respectively. Results showed significant differences in the expression of
      inflammatory markers among the fatty acid treatments and the control, with
      myristic and palmitic acids being identified as the most and linoleic acid as the
      least pro-inflammatory. This suggests that FFAs may induce low-grade inflammation
      in human coronary arterial cells and provides more information on mode of action.

PMID- 24117045
TI  - An epoxyisoprostane is a major regulator of endothelial cell function.
AB  - The goal of these studies was to determine the effect of 5,6-epoxyisoprostane,
      EI, on human aortic endothelial cells (HAEC). EI can form as a phospholipase
      product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine,
      PEIPC, a proinflammatory molecule that accumulates in sites of inflammation where
      phospholipases are also increased. To determine the effect of EI on HAEC, we
      synthesized several stereoisomers of EI using a convergent approach from the
      individual optically pure building blocks, the epoxyaldehydes 5 and 6 and the
      bromoenones 14 and 16. The desired stereoisomer of EI can be prepared from these
      materials in only six operations, and thus, large amounts of the product can be
      obtained. The trans/trans isomers had the most potent activity, suggesting
      specificity in the interaction of EI with the cell surface. EI has potent anti
      inflammatory effects in HAEC. EI strongly inhibits the production of MCP-1, a
      major monocyte chemotactic factor, and either decreases or minimally increases
      the levels of 10 proinflammatory molecules increased by PEIPC. EI also strongly
      down-regulates the inflammatory effects of IL-1beta, a major inflammatory
      cytokine. Thus EI, a hydrolytic product of PEIPC, has potent anti-inflammatory
      function. 

PMID- 24117041
TI  - Mitochondrial protein quality control in health and disease.
AB  - Progressive mitochondrial dysfunction is linked with the onset of many age
      related pathologies and neurological disorders. Mitochondrial damage can come in
      many forms and be induced by a variety of cellular insults. To preserve organelle
      function during biogenesis or times of stress, multiple surveillance systems work
      to ensure the persistence of a functional mitochondrial network. This review
      provides an overview of these processes, which collectively contribute to the
      maintenance of a healthy mitochondrial population, which is critical for cell
      physiology and survival.

PMID- 24117046
TI  - Tonic seizures of Lennox-Gastaut syndrome: periictal single-photon emission
      computed tomography suggests a corticopontine network.
AB  - PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder with
      characteristic electroclinical features but diverse etiologies. The shared
      electroclinical characteristics suggest that common cerebral networks are
      involved in generating seizures. We sought to reveal these networks by comparing
      ictal and interictal single-photon emission computed tomography (SPECT). METHODS:
      We identified 10 ictal-interictal SPECT pairs from seven patients with LGS
      (median age 11 years; range 1-38) who were studied during video
      electroencephalography (EEG)-confirmed tonic seizures. We performed a voxel-wise
      comparison of ictal and interictal SPECT studies across the group. The evolution
      of blood flow changes was explored by examining early and late injection groups.
      KEY FINDINGS: Median duration of tonic seizures was 10 s (range 6-29 s), and
      injection latency from seizure offset was -8 to 48 s. In the early injection
      group (<10 s; three studies), there was hyperperfusion over pons and cerebellar
      hemispheres (p < 0.05 cluster corrected family wise error), and hypoperfusion
      bilaterally over the pericentral region, with a trend toward hyperperfusion over
      bilateral superior and middle frontal gyri, and lateral parietal cortex. In the
      late injection group, there was hyperperfusion over midline and lateral
      cerebellar regions, with hypoperfusion widely over bilateral frontal regions.
      SIGNIFICANCE: This study suggests that the tonic seizures of LGS result from
      activity in a network, containing bilateral frontal and parietal association
      areas and the pons. We postulate that tonic seizures recruit the corticoreticular
      system, which connects frontal attentional areas to the pontine reticular
      formation, and is normally responsible for postural tone and orienting behavior.

PMID- 24117047
TI  - Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane
      conductance regulator with distinct kinetics.
AB  - BACKGROUND AND PURPOSE: Loop diuretics are widely used to inhibit the Na(+),
      K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we investigated
      the mechanism of CFTR inhibition by loop diuretics and explored the effects of
      chemical structure on channel blockade. EXPERIMENTAL APPROACH: Using the patch
      clamp technique, we tested the effects of bumetanide, furosemide, piretanide and
      xipamide on recombinant wild-type human CFTR. KEY RESULTS: When added to the
      intracellular solution, loop diuretics inhibited CFTR Cl(-) currents with potency
      approaching that of glibenclamide, a widely used CFTR blocker with some
      structural similarity to loop diuretics. To begin to study the kinetics of
      channel blockade, we examined the time dependence of macroscopic current
      inhibition following a hyperpolarizing voltage step. Like glibenclamide,
      piretanide blockade of CFTR was time and voltage dependent. By contrast,
      furosemide blockade was voltage dependent, but time independent. Consistent with
      these data, furosemide blocked individual CFTR Cl(-) channels with 'very fast'
      speed and drug-induced blocking events overlapped brief channel closures, whereas
      piretanide inhibited individual channels with 'intermediate' speed and drug
      induced blocking events were distinct from channel closures. CONCLUSIONS AND
      IMPLICATIONS: Structure-activity analysis of the loop diuretics suggests that the
      phenoxy group present in bumetanide and piretanide, but absent in furosemide and
      xipamide, might account for the different kinetics of channel block by locking
      loop diuretics within the intracellular vestibule of the CFTR pore. We conclude
      that loop diuretics are open-channel blockers of CFTR with distinct kinetics,
      affected by molecular dimensions and lipophilicity.

PMID- 24117049
TI  - Mortality in elderly ICU patients: a cohort study.
AB  - BACKGROUND: The population is aging. We examined changes in the proportion of
      elderly (>= 80 years) intensive care unit (ICU) patients during 2005-2011 and the
      association between age and mortality controlling for preexisting morbidity.
      METHODS: Through the Danish National Patient Registry, we identified a cohort of
      49,938 ICU admissions (47,596 patients) in Northern Denmark from 2005 to 2011.
      Patients were subdivided in age groups (15-49, 50-64, 65-79 and >= 80 years) and
      calendar year. We estimated 30-day and 31-365-day mortality and mortality rate
      ratios (MRRs), stratified by admission type (medical and elective/acute surgical
      patients). Mortality was compared between age groups adjusting for sex and
      preexisting morbidity using 50-64-year-olds as reference. RESULTS: The proportion
      of elderly patients increased from 11.7% of all ICU patients in 2005 to 13.8% in
      2011. Among the elderly, the 30-day mortality was 43.7% in medical, 39.6% in
      acute surgical, and 11.6% in elective surgical ICU patients. The corresponding
      adjusted 30-day MRRs compared with the 50-64-year-olds were 2.7 [95% confidence
      interval (CI) 2.5-3.0] in medical, 2.7 (95% CI 2.4-3.0) in acute surgical, and
      5.2 (95% CI 4.1-6.6) in elective surgical ICU patients. The 31-365-day mortality
      among elderly patients was 25.4% in medical, 26.9% in acute, and 11.9% in
      elective surgical ICU patients, corresponding to adjusted MRRs of 2.5 (95% CI 2.1
      2.9), 2.2 (95% CI 1.9-2.5), and 1.9 (95% CI 1.6-2.3), respectively. CONCLUSIONS:
      During 2005-2011, there was an 18% increase in the proportion of elderly ICU
      patients. Advancing age is associated with increased mortality even after
      controlling for preexisting morbidity.

PMID- 24117050
TI  - Fourier transform microwave spectrum of the nitrogen molecule-ethylene oxide
      complex: intracomplex motions.
AB  - The rotational spectra of the N2-ethylene oxide (EO) complex were measured in the
      frequency region from 4 to 27 GHz by Fourier transform microwave spectroscopy,
      paying particular attention to intracomplex motions. The isotopologues with
      enriched (15)N2 or (15)NN as a moiety were also investigated. We have observed
      spectra of a strong/weak pair for each of the ortho and para states of the (14)N2
      EO and (15)N2-EO species, which indicated that the complex existed in four
      distinct states. We interpreted, on the basis of the observed relative
      intensities, that these states were generated primarily by the exchange of the
      nitrogen atoms of the N2 moiety, followed by that of the two CH2 groups in the EO
      molecule. The (15)NN-EO species was found to consist of two isomers, one with the
      (15)N in the inner expressed as N(15)N-EO and the other in the outer position
      designated as (15)NN-EO, and the spectra of both isomers were accompanied by one
      weak set of satellites. The observed spectra were rotationally assigned by using
      sum rules and were analyzed by the asymmetric-rotor program of S-reduction, with
      the standard deviation of less than 10 kHz. We have found some of the molecular
      parameters like A, D(JK), and D(K) to be correlated between the two pairs of the
      spectra, and also, to much less extent, between the strong and weak members. The
      differences in these molecular parameters between the four sets were explained by
      the first-order Coriolis interaction between the "ground" and "excited" states
      generated by a combination of the two internal motions corresponding to the
      exchanges of the equivalent atoms and/or groups in the N2 and EO constituents of
      the complex. These internal motions were simulated by the 2-fold internal
      rotations of the two moieties. We have carried out ab initio molecular orbital
      calculations at the level of MP2 with basis sets 6-311++G(d,p), aug-cc-pVDZ, and
      aug-cc-pVTZ, to complement the information on the intracomplex motions obtained
      from the observed rotational spectra.

PMID- 24117048
TI  - Increased prevalence of sex chromosome aneuploidies in specific language
      impairment and dyslexia.
AB  - AIM: Sex chromosome aneuploidies increase the risk of spoken or written language
      disorders but individuals with specific language impairment (SLI) or dyslexia do
      not routinely undergo cytogenetic analysis. We assess the frequency of sex
      chromosome aneuploidies in individuals with language impairment or dyslexia.
      METHOD: Genome-wide single nucleotide polymorphism genotyping was performed in
      three sample sets: a clinical cohort of individuals with speech and language
      deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a
      replication cohort of individuals with SLI, from both clinical and
      epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17
      years), and a set of individuals with dyslexia (314 probands: 224 males, 90
      females; age range 7 to 18 years). RESULTS: In the clinical language-impaired
      cohort, three abnormal karyotypic results were identified in probands (proband
      yield 3.4%). In the SLI replication cohort, six abnormalities were identified
      providing a consistent proband yield (2.9%). In the sample of individuals with
      dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield
      of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO
      (Turner syndrome), and one unresolved karyotype were identified. INTERPRETATION:
      The frequency of sex chromosome aneuploidies within each of the three cohorts was
      increased over the expected population frequency (approximately 0.25%) suggesting
      that genetic testing may prove worthwhile for individuals with language and
      literacy problems and normal non-verbal IQ. Early detection of these aneuploidies
      can provide information and direct the appropriate management for individuals.

PMID- 24117052
TI  - Influence of dispersion forces and ordering on the compositions of mixed
      monolayers of alkanoic acids on nanocrystalline TiO2 films.
AB  - Lateral dispersion forces induce the ordering of n-alkanoic acids on
      nanocrystalline TiO2 films and cause the compositions of mixed monolayers to
      change. The equilibrium formation of single-component monolayers of n-alkanoic
      acids and 6-bromohexanoic acid (Br6A) on TiO2 was well-modeled by the Langmuir
      adsorption isotherm. Surface adduct formation constants were 10(3)-10(4) M(-1),
      and saturation amounts of adsorbates per projected surface area of TiO2 were on
      the order of 10(-7) mol cm(-2). The adsorption of n-heneicosanoic acid (21A)
      followed Langmuir kinetics, whereas the net rates of adsorption of shorter n
      alkanoic acids and Br6A were slower than predicted by simple Langmuir kinetics,
      suggesting that desorption was non-negligible. At high surface coverages, n
      alkanoic acids with 14 or more methylene groups formed ordered, crystalline
      monolayers, as evidenced by shifts of asymmetric and symmetric CH2 stretching
      bands in IR spectra. The extent of ordering was similar to that of self-assembled
      monolayers of alkanethiols on gold. The formation of ordered monolayers was well
      modeled by an idealized mechanism, in which adsorption and desorption followed
      Langmuir kinetics and ordering was first-order with respect to the fractional
      surface coverage of adsorbates. Dispersion forces and ordering affected the
      compositions of mixed monolayers of 21A and Br6A on TiO2 films that remained in
      contact with mixed coadsorption solutions. When the fractional surface coverage
      of 21A was sufficiently high to induce ordering, it displaced Br6A from TiO2. We
      propose that these compositional changes were driven by the stabilization of 21A
      via cohesive lateral dispersion forces. Our results reveal that mixed monolayers
      on nanocrystalline TiO2 films are dynamic and that noncovalent intermolecular
      interactions can profoundly influence their compositions and properties. 

PMID- 24117051
TI  - T cell activation is determined by the number of presented antigens.
AB  - Antigen recognition is a key event during T cell activation. Here, we introduce
      nanopatterned antigen arrays that mimic the antigen presenting cell surface
      during T cell activation. The assessment of activation related events revealed
      the requirement of a minimal density of 90-140 stimulating major
      histocompatibility complex class II proteins (pMHC) molecules per MUm(2). We
      demonstrate that these substrates induce T cell responses in a pMHC dose
      dependent manner and that the number of presented pMHCs dominates over local pMHC
      density. 

PMID- 24117053
TI  - Vascular tumours in infants. Part I: benign vascular tumours other than infantile
      haemangioma.
AB  - Vascular anomalies can be subdivided into vascular tumours and vascular
      malformations (VMs). While most VMs are present at birth and do not exhibit
      significant postnatal growth, vascular tumours are characterized by their
      dynamics of growth and (sometimes) spontaneous regression. This review focuses on
      benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic
      granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and
      noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell
      haemangioma. While some of them bear clinical resemblance to IH, they can be
      separated by age of appearance, growth characteristics and/or negative staining
      for glucose transporter 1. Separation of these tumours from IH is necessary
      because their outcome and therapeutic options are different. Semimalignant and
      malignant vascular tumours will be addressed in a separate review. 

PMID- 24117054
TI  - Monocytes: a novel drug delivery system targeting atherosclerosis.
AB  - Scavenging of reactive oxygen species (ROS) by antioxidants holds great promise
      to alleviate the symptoms of cardiovascular diseases and atherosclerosis. In
      atherosclerosis, damaged endothelial cells (EC) generate more ROS and
      inflammatory mediators, which recruit more monocytes to the EC. Antioxidants are
      good therapeutic drug candidates; however, antioxidant enzymes such as catalase
      are easily degraded by proteases in vivo and chemical mimetics of superoxide
      dismutase such as tempol and tempo require a target-specific delivery system
      since hydrophobic tempol or tempo can diffuse into any type of cells non
      specifically. Here, we report a novel monocyte-based drug delivery system
      encapsulating either catalase or tempol/tempo. Monocyte as a novel drug delivery
      vehicle offers advantages over other delivery systems due to its target
      specificity to damaged EC. The delivery system can also be easily fabricated in
      biological conditions and keeps antioxidants active. Membrane impermeable
      catalase with protease inhibitors was formulated in monocytes via a
      hypotonic/resealing method and membrane permeable tempol/tempo were encapsulated
      in monocytes via passive diffusion with 40-60% encapsulation efficiency.
      Antioxidant-loaded monocytes targeted EC and the antioxidants scavenged more than
      90% intracellular ROS generated by cytokines or exogenous ROS. We anticipate
      numerous applications of the monocyte-based drug delivery system, given its
      target specificity to activated EC.

PMID- 24117056
TI  - Moisture condensation behavior of hierarchically carbon nanotube-grafted carbon
      nanofibers.
AB  - Hierarchical micro/nanosurfaces with nanoscale roughness on microscale uneven
      substrates have been the subject of much recent research interest because of
      phenomena such as superhydrophobicity. However, an understanding of the effect of
      the difference in the scale of the hierarchical entities, i.e., nanoscale
      roughness on microscale uneven substrates as opposed to nanoscale roughness on (a
      larger) nanoscale uneven surface, is still lacking. In this study, we
      investigated the effect of the difference in scale between the nano- and
      microscale features. We fabricated carbon nanotube-grafted carbon nanofibers
      (CNFs) by dispersing a catalyst precursor in poly (acrylonitrile) (PAN) solution,
      electrospinning the PAN/catalyst precursor solution, carbonization of electrospun
      PAN nanofibers, and direct growth of carbon nanotubes (CNTs) on the CNFs. We
      investigated the relationships between the catalyst concentrations, the size of
      catalyst nanoparticles on CNFs, and the sizes of CNFs and CNTs. Interestingly,
      the hydrophobic behavior of micro/nano and nano/nano hierarchical surfaces with
      water droplets was similar; however a significant difference in the water
      condensation behavior was observed. Water condensed into smaller droplets on the
      nano/nano hierarchical surface, causing it to dry much faster. 

PMID- 24117055
TI  - Neuroprotection effect of interleukin (IL)-17 secreted by reactive astrocytes is
      emerged from a high-level IL-17-containing environment during acute
      neuroinflammation.
AB  - An increase in interleukin (IL)-17A-producing cells, particularly at sites of
      tissue inflammation, is observed frequently, yet the mechanism is not fully
      understood. This study aims to dissect the role of IL-17 in autoimmunity-mediated
      neuroinflammation. The cytokine milieu containing elevated IL-17, which often
      appears in active states of autoimmunity, was mimicked in vitro by a supernatant
      obtained from rat peripheral blood monocytes stimulated with phorbol mystistate
      acetate (PMA)/ionomycin. The application of such inflammatory media on only
      primary cultured cerebellar granule neurones resulted in significant apoptosis,
      but the presence of astrocytes largely prevented the effect. The supernatants of
      the stimulated astrocytes, especially those that contained the highest level of
      IL-17, achieved the best protection, and this effect could be blocked by anti-IL
      17 antibodies. Protein IL-17 inhibited intracellular calcium increase and
      protected the neurones under inflammatory attack from apoptosis. IL-17, but not
      interferon (IFN)-gamma, in the inflammatory media contributed to astrocyte
      secretion of IL-17, which depended on the Janus kinase/signal transducers and
      activators of transcription (JAK/STAT) pathway activation. The astrocytes that
      were treated with IL-17 alone or with prolonged treatment of the inflammatory
      media failed to produce sufficient levels of IL-17. Moreover, confirmatory data
      were obtained in vivo in a monophasic experimental autoimmune uveitis (EAU) in
      Lewis rats; in this preparation, the high-level IL-17-containing the cytokine
      milieu was demonstrated, along with IL-17 secretion by the resident neural cells.
      The antagonism of IL-17 at a late stage disturbed the disease resolution and
      resulted in significant neural apoptosis. Our data show a dynamic role of IL-17
      in the maintenance of homeostasis and neuroprotection in active
      neuroinflammation. 

PMID- 24117057
TI  - Within-subject correlations between evening-related changes in body temperature
      and melatonin in the spinal cord injured.
AB  - BACKGROUND: Individuals with a spinal cord injury (SCI) demonstrate altered
      circadian variation in thermoregulatory control. Recently, we reported that
      tetraplegia is associated with a blunted release of melatonin in the evening. In
      order to examine whether this finding relates to circadian thermoregulation, we
      compared the correlations between evening changes in melatonin, core and skin
      temperature between thoracic and cervical SCI and able-bodied participants.
      METHODS: In 10 able-bodied, 9 paraplegic and 8 tetraplegic participants, we
      measured, between 1900 and 2300 h, core temperature, proximal skin temperature
      (above and below the level of the lesion) and physical activity. Salivary
      melatonin was also sampled during this period and analyzed using enzyme linked
      immunosorbant assay. RESULTS: Between 1900 and 2300 h, core and upper limb skin
      temperature gradually decreased in all groups (p = 0.01). A significant group *
      time interaction was evident in lower body skin temperature (p = 0.03). Lower
      body skin temperature was significantly higher in able-bodied controls compared
      with tetraplegics between 1900 and 2000 h (p < 0.05). In able-bodied and
      paraplegic participants, the changes in melatonin and core temperature were
      inversely correlated (r = -0.44 and -0.54, respectively, both p = 0.01).
      Melatonin and mean skin temperature changes were also inversely correlated (able
      bodied controls: r = -0.24; p = 0.05 and paraplegics: r = -0.30; p= 0.02).
      CONCLUSION: The inverse correlation between evening changes in melatonin and
      thermoregulation is of a similar magnitude in paraplegic and able-bodied
      controls. In contrast, changes in skin temperature, below the level of the
      lesion, are unrelated to changes in melatonin in tetraplegics.

PMID- 24117058
TI  - Circadian alterations of reproductive functional markers in male rats exposed to
      1800 MHz radiofrequency field.
AB  - In this study, we explored the circadian effects of daily radiofrequency field
      (RF) exposure on reproductive functional markers in adult male Sprague-Dawley
      rats. Animals in circadian rhythm (as indicated by melatonin measurements), were
      divided into several groups and exposed to 1800 MHz RF at 205 MUw/cm(2) power
      density (specific absorption rate 0.0405 W/kg) for 2 h/day for 32 days at
      different zeitgeber time (ZT) points, namely, ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20.
      Sham-exposed animals were used as controls in the study. From each rat,
      testicular and epididymis tissues were collected and assessed for testosterone
      levels, daily sperm production and sperm motility, testis marker enzymes gamma-GT
      and ACP, cytochrome P450 side-chain cleavage (p450cc) mRNA expression, and
      steroidogenic acute regulatory protein (StAR) mRNA expression. Via these
      measurements, we confirmed the existence of circadian rhythms in sham-exposed
      animals. However, rats exposed to RF exhibited a disruption of circadian rhythms,
      decreased testosterone levels, lower daily sperm production and sperm motility,
      down-regulated activity of gamma-GT and ACP, as well as altered mRNA expression
      of cytochrome P450 and StAR. All of these observations were more pronounced when
      rats were exposed to RF at ZT0. Thus, our findings indicate potential adverse
      effects of RF exposure on male reproductive functional markers, in terms of both
      the daily overall levels as well as the circadian rhythmicity. 

PMID- 24117059
TI  - Is ADHD an early stage in the development of borderline personality disorder?
AB  - BACKGROUND: Several studies report associations between adults with borderline
      personality disorder (BPD) and a history of attention-deficit hyperactivity
      (ADHD) symptoms in childhood. AIMS: To explore the association between BPD and a
      history of ADHD in childhood. METHOD: A comprehensive search of EMBASE, PsychInfo
      and Medline and hand-searching yielded 238 "hits". Fifteen articles were found to
      have sufficient quality and relevance to be included in the final review. The
      data were considered in six possible explanatory psychopathological models of the
      association between ADHD and BPD. RESULTS: Most of the 15 articles showed a
      statistical association between ADHD and BPD. The data, most strongly provided a
      basis for the hypotheses that ADHD is either an early developmental stage of BPD,
      or that the two disorders share an environmental and genetic aetiology.
      Furthermore, one of the disorders seems to give a synergic effect, reinforce the
      other or complicate the disorders. In one prospective study, the risk factor for
      children with ADHD to develop BPD was as high as odds ratio 13.16. No studies
      have looked at treatment of ADHD as a mediator of the risk for BPD. CONCLUSIONS:
      Many studies pointed at shared aetiology or the risk for development of one
      disorder, when the other disorder is present. The data do not evaluate how
      treatment factors or other factors mediate the risk or how overlap of diagnostic
      criteria adds to the statistical association. More research is much needed, in
      particular studies looking at early intervention and which treatment of ADHD that
      might prevent later development of BPD.

PMID- 24117061
TI  - Bringing habitat information into statistical tests of local adaptation in
      quantitative traits: a case study of nine-spined sticklebacks.
AB  - Detection of footprints of historical natural selection on quantitative traits in
      cross-sectional data sets is challenging, especially when the number of
      populations to be compared is small and the populations are subject to strong
      random genetic drift. We extend a recent Bayesian multivariate approach to
      differentiate between selective and neutral causes of population differentiation
      by the inclusion of habitat information. The extended framework allows one to
      test for signals of selection in two ways: by comparing the patterns of
      population differentiation in quantitative traits and in neutral loci, and by
      comparing the similarity of habitats and phenotypes. We illustrate the framework
      using data on variation of eight morphological and behavioral traits among four
      populations of nine-spined sticklebacks (Pungitius pungitius). In spite of the
      strong signal of genetic drift in the study system (average FST = 0.35 in neutral
      markers), strong footprints of adaptive population differentiation were uncovered
      both in morphological and behavioral traits. The results give quantitative
      support for earlier qualitative assessments, which have attributed the observed
      differentiation to adaptive divergence in response to differing ecological
      conditions in pond and marine habitats. 

PMID- 24117060
TI  - Spectral evolution of a photochemical protecting group for orthogonal two-color
      uncaging with visible light.
AB  - Caged compounds are molecules rendered functionally inert by derivatization with
      a photochemical protecting group. We describe the design logic behind the
      development of a diethylaminocoumarin (DEAC) caging chromophore, DEAC450, that
      absorbs blue light strongly (epsilon450 = 43,000 M(-1) cm(-1)) and violet light
      11-fold more weakly. The absorption minimum is in the wavelength range (340-360
      nm) that is traditionally used for photolysis of many widely used nitroaromatic
      caged compounds (e.g., 4-carboxymethoxy-5,7-dinitroindolinyl(CDNI)-GABA). We used
      this chromophore to synthesize DEAC450-caged cAMP and found this probe was very
      stable toward aqueous hydrolysis in the electronic ground state but was
      photolyzed with a quantum efficiency of 0.78. When DEAC450-cAMP and CDNI-GABA
      where co-applied to striatal cholinergic interneurons, the caged compounds were
      photolyzed in an chromatically orthogonal manner using blue and violet light so
      as to modulate the neuronal firing rate in a bidirectional way. 

PMID- 24117062
TI  - Efficacy of Integrated Rehabilitation Techniques of Traditional Chinese Medicine
      for ischemic stroke: a randomized controlled trial.
AB  - This study aimed to determine the efficacy of Integrated Rehabilitation
      Techniques of Traditional Chinese Medicine (IRT-TCM) on patients with ischemic
      stroke as an alternative therapy to conventional rehabilitation techniques. Sixty
      nine patients with ischemic stroke were randomly assigned to receive either IRT
      TCM (intervention group, n = 46) or conventional rehabilitation techniques
      (control group, n = 23). The IRT-TCM consisted of a sequential combination of
      acupuncture and massage techniques. The Fugl-Meyer Assessment (FMA), National
      Institutes of Health Stroke Scale (NIHSS), Barthel index (BI) and modified Rankin
      Scale (mRS) were measured on day 0 (baseline, before treatment), day 21, and day
      90. We observed that the scores in FMA and BI were increased, and NIHSS were
      decreased in both groups on day 21 and 90, compared with the baseline (day 0).
      Furthermore, significantly better scores in FMA of lower limbs and NIHSS were
      found in patients treated with IRT-TCM on day 21 and 90. For mRS, the percentage
      of patients ranking 0 and 1 in the intervention group presented a striking
      contrast to the control group on day 90 but with no significant difference. The
      results indicated that, as a feasible alternative therapy, IRT-TCM is beneficial
      for patients with ischemic stroke. Further research with larger sample size, long
      term observation, and strict blinding are still in need to confirm the efficacy
      of IRT-TCM. 

PMID- 24117063
TI  - Therapeutic effects of Chinese osteopathy in patients with lumbar disc
      herniation.
AB  - A clinical study was conducted in 72 lumbar disc herniation (LDH) patients and 40
      asymptomatic subjects to evaluate the efficacy of Feng's spinal manipulation
      (FSM). FSM was performed twice a week for less than 20 days. Changes in the
      symmetrical index of spinal column (SISC) and quantified symptom index (QSI)
      before and after FSM in both groups were collected. The QSI consisted of the
      visual analogue scale (VAS), score of the Japanese Orthopedic Association, and
      straight leg raising test, for measurement of pain perception, dysfunction of
      lower limb extension or flexion, and symptomatic relief. A correlation analysis
      was conducted to compare the difference in protruded nucleus pulposus size using
      computerized projection grating profilometry, SISC, and QSI before and after the
      therapy. The results showed that the SISC and QSI significantly decreased after
      treatment in the LDH group (p < 0.01). The SISC before and after treatment was
      closely correlated with the improvement of QSI, although there was no change in
      protruded nucleus pulposus following the therapy. Among the five components in
      SISC, the LR was found to be an ideal indicator for evaluation of the real
      circumstances in LDH patients. Our data suggested that FSM achieved satisfactory
      therapeutic effects in relieving the symptom of LDH while no effects were
      observed in asymptomatic subjects. 

PMID- 24117064
TI  - Characteristics of female and male visitors to practitioners of acupuncture in
      the HUNT3 Study.
AB  - Characteristics of female and male visitors to practitioners of acupuncture were
      investigated in a large cross-sectional adult population in Central Norway. A
      total population health survey, HUNT3, conducted in 2008 with 50,827 respondents
      provided the data. Demographic variables, lifestyle, health, and use of
      conventional medicine were analyzed using multivariable logistic regression
      models. The one year prevalence of visiting a practitioner of acupuncture was
      5.7% for females and 2.2% for males. Visitors of both genders were five times
      more likely to have had somatic complaints in the preceding year and were 2-3
      times more likely to report poor global health than female or male non-visitors.
      Also, visitors of both genders were more likely to do hard physical activities
      every week, and they were less likely to live alone or be daily smokers. Further,
      female visitors were characterized by having higher education and were more
      likely to have a paid job than other females. Corresponding differences were not
      seen among males. Age showed limited associations with being a visitor, and for
      females only. Valid for both genders, our findings draw a picture of visitors to
      acupuncture treatment as persons who actively contribute to promoting their
      health through lifestyle choices of physical activity and non-smoking while
      simultaneously having worse global health and higher burdens of somatic
      complaints than other adults. In contrast to males, it is suggested that females
      may be more dependent on personal income, as indicated by higher education and
      being in a paid job, in choosing acupuncture treatment in addition to
      conventional medicine. 

PMID- 24117065
TI  - Systematic review and meta-analysis of traditional Chinese medicine in the
      treatment of migraines.
AB  - Migraine is a chronic disorder characterized by recurrent moderate to severe
      headaches often in association with a number of autonomic nervous system
      symptoms. It is a common disease and incidence has increased yearly. Chinese
      medical treatments are popularly used in Asian countries, although they vary in
      effectiveness. In this study, we applied a systematic review method and combined
      meta-regression with meta-subgroup analysis to explore heterogeneity of clinical
      therapeutic efficacy upon meta-analysis of randomized controlled Chinese medical
      treatments for migraine. We also aimed to provide a more effective Chinese
      prescription and to advance the knowledge in evaluating validity of preventing or
      alleviating migraine symptoms with Chinese medical treatments. Twenty randomized
      migraine control trails, including 2246 patients, were collected from online
      databases: PubMed, MEDLINE, EMBASE, CENTRAL of Cochrane Library, CBM, integrated
      version of CMCI/CMCC, TCM online, CDFD, and CMFD from January 2000 to December
      2011. The results showed that the major factors influencing therapeutic efficacy
      were either the specific medicine form of or its prescription type (p < 0.05).
      The use of TCM decoctions, especially those that condition the viscera, treat
      from the perspective of "wind", and target the Shaoyang gateway, could be the
      best migraine treatment in clinical TCM practice (RR > 1.30).

PMID- 24117066
TI  - Curcumin induces ABCA1 expression and apolipoprotein A-I-mediated cholesterol
      transmembrane in the chronic cerebral hypoperfusion aging rats.
AB  - Cerebral hypoperfusion or aging often results in the disturbances of cholesterol
      and lipoprotein, which have been well depicted as a common pathological status
      contributing to neurodegenerative diseases such as vascular dementia (VaD) and
      Alzheimer's dementia (AD). The pathway of the liver X receptor-beta (LXR
      beta)/retinoic X receptor-alpha (RXR-alpha)/ABCA1 plays a vital role in
      lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely
      used. It has been reported that curcumin can reduce the levels of cholesterol in
      serum, but the underlying mechanisms are poorly understood. In this study, we
      evaluated the effects of curcumin on the cholesterol level in brain, vascular
      cognitive impairment and explored whether the mechanisms for those effects are
      through activating LXR-beta/RXR-alpha and ABCA1 expression and apoA-I. With a
      Morris water test, we found that curcumin treatment could attenuate cognitive
      impairment. With HE and Nissl staining, we found that curcumin could
      significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile,
      the expression of LXR-beta, RXR-alpha, ABCA1 and apoA-I mRNA and protein were
      increased in a dose-dependent manner after curcumin treatment. Interestingly,
      both serum HDL cholesterol and total cholesterol levels were statistically higher
      in the curcumin treatment group than those other groups. We conclude that
      curcumin has the ability to activate permissive LXR-beta/RXR-alpha signaling and
      thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane
      transportation, which is a new preventive and therapeutic strategy for
      cerevascular diseases.

PMID- 24117067
TI  - GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of
      the trigeminal subnucleus caudalis in mice.
AB  - The plant Withania somnifera (WS), also known as Ashwagandha, has been used
      widely in traditional medicine systems in India and Nepal (Ayurveda), and has
      been accepted to cure various ailments. In this study, the whole-cell patch clamp
      technique was performed to examine the mechanism of action of WS on the SG
      neurons of the Vc from mouse brainstem slices. In whole-cell patch clamp mode,
      methanol extract of Withania somnifera (mWS) induced short-lived and repeatable
      inward currents in all SG neurons tested (31.3 +/- 8.51 pA, n = 7) using a high
      chloride pipette solution. The mWS-induced inward currents were concentration
      dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated
      Na (+) channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, AP5, an
      NMDA receptor antagonist and strychnine, a glycine receptor antagonist. The mWS
      induced currents were blocked by picrotoxin, a GABAA receptor antagonist. These
      results show that mWS has an inhibitory effects on SG neurons of the Vc through
      GABAA receptor-mediated activation of chloride ion channels, indicating that mWS
      contains compounds with sedative effects on the central nervous system. These
      results also suggest that mWS may be a potential target for modulating orofacial
      pain processing.

PMID- 24117068
TI  - Mitochondrial protective effects of Myrica rubra extract against acetaminophen
      induced toxicity.
AB  - The present study investigates the hepatoprotective activity of Myrica rubra
      Sieb. et Zucc. extract (MCE) against acetaminophen (AAP)-induced liver damage and
      elucidates the possible mechanisms behind the hepatoprotection observed. Serum
      alanine aminotransferase and serum aspartate aminotransferase activities were
      detected and liver histopathology was observed. Mitochondrial swelling,
      mitochondrial membrane potential, and voltage-dependent anion channel (VDAC) gene
      transcription were also investigated. The results showed that 50, 150, and 450
      mg/kg MCE could restore AAP-induced changes in mice liver in a dose-dependent
      manner. The mechanisms behind the hepatoprotective effects of MCE may be related
      to the mitochondrial protection of liver cells, especially of VDAC, an important
      protein on the outer membrane of the mitochondria.

PMID- 24117069
TI  - Anti-inflammatory effects of danshen on human vascular endothelial cells in
      culture.
AB  - Inflammation plays a crucial role in the pathophysiology of atherosclerosis.
      Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin
      play important roles as key regulators of the inflammatory process in
      atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine
      for therapy of cardiovascular diseases such as coronary artery disease. The aim
      of the present study was to evaluate the protective effects of DS with respect to
      possible anti-inflammatory effects. Human umbilical vein endothelial cells as
      well as platelets were incubated with an extract of DS or one of its major
      ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic
      acid (Protoc) under tumor necrosis factor (TNF)-alpha or ADP stimulation.
      Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed
      via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant
      protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were
      examined via luminex based analysis. Treatment with DS attenuated TNF-alpha
      induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as
      well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell
      supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS
      and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced
      expression and release of adhesion molecules, cytokines and chemokines as well as
      ADP-induced expression of platelet P-selectin. Because of the key roles of
      inflammatory mediators in the etiology of atherosclerosis, this work provides
      useful insight in understanding the pharmacological efficacy of Chinese herbal
      medicine.

PMID- 24117070
TI  - Novel effect of paeonol on the formation of foam cells: promotion of LXRalpha
      ABCA1-dependent cholesterol efflux in macrophages.
AB  - Paeonol, a phenolic component purified from Paeonia suffruticosa (Cortex Moutan),
      is used in traditional Chinese medicine to treat inflammatory diseases. However,
      little is known about the effect of paeonol on cholesterol metabolism. We
      investigated the efficacy of paeonol on cholesterol metabolism and the underlying
      mechanism in macrophages and apolipoprotein E deficient (apoE(-/-)) mice.
      Treatment with paeonol markedly attenuated cholesterol accumulation induced by
      oxidized LDL in macrophages, which was due to increased cholesterol efflux.
      Additionally, paeonol enhanced the mRNA and protein expression of ATP-binding
      membrane cassette transport protein A1 (ABCA1) but did not alter the protein
      level of ABCG1 or other scavenger receptors. Inhibition of ABCA1 activity with a
      pharmacological inhibitor, neutralizing antibody or small interfering RNA
      (siRNA), negated the effects of paeonol on cholesterol efflux and cholesterol
      accumulation. Furthermore, paeonol induced the nuclear translocation of liver X
      receptor alpha (LXRalpha) by increasing its activity. siRNA knockdown of LXRalpha
      abolished the paeonol-induced upregulation of ABCA1, promotion of cholesterol
      efflux and suppression of cholesterol accumulation. Moreover, atherosclerotic
      lesions, hyperlipidemia and systemic inflammation were reduced and the protein
      expression of ABCA1 was increased in aortas of paeonol-treated apoE(-/-) mice.
      Paeonol may alleviate the formation of foam cells by enhancing LXRalpha-ABCA1
      dependent cholesterol efflux.

PMID- 24117071
TI  - Salvia miltiorrhiza (dan shen) significantly ameliorates colon inflammation in
      dextran sulfate sodium induced colitis.
AB  - Inflammatory bowel disease increases the risks of human colorectal cancer. In
      this study, the effects of Salvia miltiorrhiza extract (SME) on chemically
      induced colitis in a mouse model were evaluated. Chemical composition of SME was
      determined by HPLC analysis. A/J mice received a single injection of AOM 7.5
      mg/kg. After one week, these mice received 2.5% DSS for eight days, or DSS plus
      SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity
      index (DAI). Body weight and colon length were also measured. The severity of
      inflammatory lesions was further evaluated by colon tissue histological
      assessment. HPLC assay showed that the major constituents in the tested SME were
      danshensu, protocatechuic aldehyde, salvianolic acid D, and salvianolic acid B.
      In the model group, the DAI score reached its highest level on Day 8, while the
      SME group on both doses showed a significantly reduced DAI score (both p < 0.01).
      As an objective index of the severity of inflammation, colon length was
      significantly shorter in the model group than the vehicle group. Treatment with
      25 and 50 mg/kg of SME inhibited the shortening of colon in a dose-related manner
      (p < 0.05 and p < 0.01, respectively). SME groups also significantly reduced
      weight reduction (p < 0.05). Colitis histological data supported the
      pharmacological observations. Thus, Salvia miltiorrhiza could be a promising
      candidate in preventing and treating colitis and in reducing the risks of
      inflammation-associated colorectal cancer.

PMID- 24117072
TI  - Moringa fruit inhibits LPS-induced NO/iNOS expression through suppressing the NF
      kappa B activation in RAW264.7 cells.
AB  - In this study, we evaluated the anti-inflammatory effects of moringa (Moringa
      oleifera Lam.), a natural biologically active substance, by determining its
      inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)
      stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa
      (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose
      dependent manner. The moringa fruit extract most effectively inhibited LPS
      induced NO production and levels of inducible nitric oxide synthase (iNOS). The
      moringa fruit extract also was shown to suppress the production of inflammatory
      cytokines including IL-1beta, TNF-alpha, and IL-6. Furthermore, moringa fruit
      extract inhibited the cytoplasmic degradation of I kappa B -alpha and the nuclear
      translocation of p65 proteins, resulting in lower levels of NF -kappa B
      transactivation. Collectively, the results of this study demonstrate that moringa
      fruit extract reduces the levels of pro-inflammatory mediators including NO , IL
      1beta, TNF-alpha, and IL-6 via the inhibition of NF -kappa B activation in
      RAW264.7 cells. These findings reveal, in part, the molecular basis underlying
      the anti-inflammatory properties of moringa fruit extract.

PMID- 24117073
TI  - Genistein suppresses the isoproterenol-treated H9c2 cardiomyoblast cell apoptosis
      associated with P-38, Erk1/2, JNK, and NFkappaB signaling protein activation.
AB  - Heart disease (HD) is associated with estrogen and therefore gender and
      menopausal status. In addition, clinical evidence shows that increased serum
      norepinephrine is found in patients with HD. Therefore, this study aimed to
      investigate the cardio-protective effect of genistein, a selective estrogen
      receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells
      treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro
      model, image data and results from western blotting shown that ISO treatment was
      capable of inducing cellular apoptosis, especially the mitochondrial dependent
      pathway. Treatment of genistein could suppress the expression of mitochondrial
      pro-apoptotic proteins including Bad, caspase-8, caspase-9, and caspase-3 in H9c2
      treated with ISO. By contrast, several survival proteins were expressed in H9c2
      treated with genistein, such as phosphor (p)-Akt, p-Bad, and p-Erk1/2.
      Furthermore, we confirmed that the protective role of genistein was partially
      mediated through the expression of Erk1/2, Akt, and NF kappa B proteins by adding
      several pathway inhibitors. These in vitro data suggest that genistein may be a
      safe and natural SERM alternative to hormone therapy in cardio-protection.

PMID- 24117074
TI  - 20(S)-protopanaxadiol triggers mitochondrial-mediated apoptosis in human lung
      adenocarcinoma A549 cells via inhibiting the PI3K/Akt signaling pathway.
AB  - 20(S)-Protopanaxadiol (PPD), an aglycone saponin ginsenoside isolated from Panax
      quinquefolium L, has been shown to inhibit the growth and proliferation in
      several cancer lines. However, the underlying molecular mechanisms remain poorly
      understood. In this study, we investigated the apoptosis-induced effects and the
      mechanism of 20(S)-PPD on human lung adenocarcinoma A549 cells. 20(S)-PPD showed
      a potent antiproliferative activity against A549 cells by triggering apoptosis.
      20(S)-PPD-induced apoptosis was characterized by a dose-dependent loss of the
      mitochondrial membrane, release of cytochrome c, second mitochondria-derived
      activator of caspase (Smac) and apoptosis-inducing factor (AIF), activation of
      caspase-9/-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Caspase
      dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to
      attenuate 20(S)-PPD-induced apoptosis. After treatment with 20(S)-PPD, the
      proportion of A549 cells at the G0/G1 phase increased, while cells at the S and
      G2/M phases decreased. Furthermore, 20(S)-PPD also triggered down-regulation of
      phosphorylated Akt (Ser473/Thr308) and glycogen synthase kinase 3beta (GSK
      3beta). Knockdown of GSK 3beta with siRNA promoted the apoptotic effects of 20(S)
      PPD. These results revealed an unexpected mechanism of action for this unique
      ginsenoside: triggering a mitochondrial-mediated, caspase-dependent apoptosis via
      down-regulation of the PI3K/Akt signaling pathway in A549 cells. Our findings
      encourage further studies of 20(S)-PPD as a promising chemopreventive agent
      against lung cancer.

PMID- 24117075
TI  - Wedelia chinensis inhibits nasopharyngeal carcinoma CNE-1 cell growth by inducing
      G2/M arrest in a Chk1-dependent pathway.
AB  - Although Wedelia chinensis, an herb in traditional Chinese medicine, has been
      widely used for the treatment of inflammation, the effects of W. chinensis on
      cancer cell growth and the related molecular mechanisms behind these effects have
      largely remained unexplored to date. In the present study, W. chinensis plant
      extracts were obtained using either ethanol (E), petroleum ether (PE), ethyl
      acetate (EA) or butyl alcohol (BA). Then, extracts were examined for bioactivity
      in vitro via MTT assay in five human cancer cell lines. Our results showed that
      one subfraction of the EA extract (EA6) was cytotoxic to nasopharyngeal carcinoma
      (NPC) CNE-1 cells, among all cell lines evaluated. Treatment of CNE-1 cells with
      EA6 resulted in significant G2/M cell cycle arrest and modest apoptosis. EA6
      induced Chk1 activation and inhibition of Chk1 in CNE-1 cells by RNA interference
      (RNAi) markedly abrogated EA6-mediated G2/M arrest and abolished EA6-induced
      cytotoxicity. EA6 treatment resulted in notable reduction of c-myc expression in
      CNE-1 cells, whereas silencing Chk1 inhibited such effects of EA6. Our results
      indicate that Chk1 is a novel molecular target of EA6 in NPC cells and also
      suggest an intervention strategy for NPC by EA6 exploring its molecular
      mechanisms of action.

PMID- 24117076
TI  - Cytotoxic effect and induction of apoptosis in human cervical cancer cells by
      Antrodia camphorata.
AB  - Antrodia camphorata is a Chinese herb indigenous to Taiwan. Previous reports
      demonstrated that it could induce apoptosis in some cancer cells. The purpose of
      this study was to investigate the apoptotic effect of the crude extract of A.
      camphorata in cervical cancer cells. Two human cervical cancer cell lines, HeLa
      and C-33A, were treated with extract of A. camphorata (10-1000 MUg/mL). We found
      that A. camphorata extract was cytotoxic to both cervical cancer cells in a dose-
      and time-dependent manner as examined by MTT assay. Treatment with A. camphorata
      extract at 400 MUg/mL induced a 2.3- and 4.4-fold increase in oligonucleosome
      formation from the cleaved chromosomal DNA in HeLa and C-33A cells, respectively.
      A. camphorata extract also activated caspase-3, -8, and -9 activities and
      increased the cytosolic level of cytochrome c in both cell lines as the dosage
      increased. Furthermore, A. camphorata extract increased expressions of Bak, Bad
      and Bim, while decreasing expressions of Bcl-2 and Bcl-xL of the Bcl-2 family
      proteins in HeLa and C-33A cells. The expression of IAP proteins, XIAP and
      survivin, was also decreased in both cervical cancer cells after treatment with
      A. camphorata. Our in vitro study suggests that A. camphorata is cytotoxic to
      cervical cancer cells through both extrinsic and intrinsic apoptotic mechanisms.
      It could be used as a novel phytotherapeutic agent or auxiliary therapy in the
      treatment of cervical cancer.

PMID- 24117077
TI  - Rapid identification of chemical constituents in traditional Chinese medicine
      fufang preparation xianling gubao capsule by LC-linear ion trap/Orbitrap mass
      spectrometry.
AB  - The traditional Chinese medicine fufang preparation "Xian-Ling-Gu-Bao" capsule
      (XLGB), which is composed of six herbal medicines, is popularly used for the
      treatment of osteoporosis. A reliable and effective method using LC-linear ion
      trap (LTQ)/Orbitrap mass spectrometry for rapid screening and identification of
      chemical constituents in "Xian-Ling-Gu-Bao" capsule is described in this paper.
      Based on the UV spectrum, mass spectrum, and the chemical components isolated
      from the original plants of XLGB, 118 compounds were identified or tentatively
      characterized, including 58 flavonoid glycosides, six prenylated flavonones, five
      prenylated isoflavones, six prenylated chalcones, four xanthone C-glycosides, 13
      saponins, eight phenolic acids, five coumarins, three lignans, three iridoids,
      five phenethyl alcohol glycosides, one tanshinone and one alkaloid. This work
      might be helpful for the quality control and further pharmacokinetic studies of
      XLGB, and provided a good example for the rapid identification of chemical
      constituents in traditional Chinese medicine fufang preparation. Moreover, the
      identification strategy for the linkages of sugar residues in flavonol O
      glycosides was summarized in the study. The diagnostic fragment ions at m/z 185
      [C12H9O2] and 157 [C11H9O], which distinguish C-6 and C-8 prenylated flavonoids,
      were reported for the first time.

PMID- 24117078
TI  - Bench-scale evaluation of ferrous iron oxidation kinetics in drinking water:
      effect of corrosion control and dissolved organic matter.
AB  - Corrosion control strategies are important for many utilities in maintaining
      water quality from the water treatment plant to the customers' tap. In drinking
      water with low alkalinity, water quality can become significantly degraded in
      iron-based pipes if water utilities are not diligent in maintaining proper
      corrosion control. This article reports on experiments conducted in bicarbonate
      buffered (5 mg-C/L) synthetic water to determine the effects of corrosion control
      (pH and phosphate) and dissolved organic matter (DOM) on the rate constants of
      the Fe(II) oxidation process. A factorial design approach elucidated that pH (P =
      0.007, contribution: 42.5%) and phosphate (P = 0.025, contribution: 22.7%) were
      the statistically significant factors in the Fe(II) oxidation process at a 95%
      confidence level. The comprehensive study revealed a significant dependency
      relationship between the Fe(II) oxidation rate constants (k) and phosphate-to-
      Fe(II) mole ratio. At pH 6.5, the optimum mole ratio was found to be 0.3 to
      reduce the k values. Conversely, the k values were observed to increase for the
      phosphate-to- Fe(II) mole ratio > 1. The factorial design approach revealed that
      chlorine and DOM for the designated dosages did not cause a statistically
      significant (alpha = 0.05, P > 0.05)change in rate constants. However, an
      increment of the chlorine to ferrous iron mole ratio by a factor of ~ 2.5
      resulted in an increase k values by a factor of ~ 10. This study conclusively
      demonstrated that the lowest Fe(II) oxidation rate constant was obtained under
      low pH conditions (pH <= 6.5), with chlorine doses less than 2.2 mg/L and with a
      phosphate-to-Fe(II) mole ratio ~ 0.3 in the iron water systems.

PMID- 24117079
TI  - Effect of a water-based drilling waste on receiving soil properties and plants
      growth.
AB  - This investigation was undertaken to determine the relative effects of
      recommended land spraying while drilling (LWD) loading rate application for a
      source of water-based drilling waste material on selected soil properties and
      phytotoxicity. Drilling waste material was obtained from a well where a nitrate
      gypsum water based product was used to formulate the drilling fluid. The fluid
      and associated drill cuttings were used as the drilling waste source to conduct
      the experiment. The study was carried out in triplicate and involved five plant
      species, four drilling waste loading rates and a representative agricultural soil
      type in Alberta. Plant growth was monitored for a period of ten days. Drilling
      waste applied at 10 times above the recommended loading rate improved the growth
      and germination rate of all plants excluding radish. Loading rates in excess of
      40 and 50 times had a deleterious effect on radish, corn and oat but not on
      alfalfa and barley. Germination rate decreased as waste loading rate increased.
      Effects on soil physical and chemical properties were more pronounced at the 40
      and 50 times exceeding recommended loading rate. Significant changes in soil
      parameters occurred at the higher rates in terms of increase in soil porosity,
      pH, EC, hydraulic conductivity, SAR and textural classification. This study
      indicates that the applications of this type of water based drill cutting if
      executed at an optimal loading rate, may improve soil quality and results in
      better plant growth.

PMID- 24117080
TI  - Effect of the interaction between dye and acetic acid on the decomposition of
      Basic Green 4 with additive by ozone.
AB  - This research investigated the ozonation of Basic Green 4 (BG4) under the
      presence of acetic acid (AA). This acid is used as a textile additive for many
      industrial dyes derived from triphenylmethane. Determining the effect of this
      additive on discoloration, degradation dynamics, and final by-product
      distribution is the main objective of this study. The reaction system was the
      ozonation of a dye solution in co-solvents. This solution (dye and AA) was
      considered a simplified version of real BG4 dyeing wastewaters supplied with
      additives. The dye concentration was set to 50, 150, and 250 mg/L without pH
      adjustment (pH = 3). This low value was forced by the AA. Ozonation reaction with
      dye was mainly done by a direct molecular mechanism. The discoloration dynamics
      of BG4 without and with the additive were determined by ultraviolet and visible
      wavelength spectroscopy. The dye decomposition and the intermediate and final
      product formation-decomposition dynamics were followed by high-performance liquid
      chromatography. The effects of AA in the ozonation results were significant in
      the following ways: 1) a possible complex, formed between AA and the dye, changed
      ozone consumption; 2) the presence of additive decelerated the dye discoloration
      and decomposition; and 3) the number of by-products was dissimilar in both
      systems, with and without the additive the ozonation. The accumulation of organic
      acids with low molecular weight was determined in both systems, with and without
      the additive. Only one by-product was obtained in ozonation when AA participated
      in the reactor. A possible reaction mechanism is proposed for the system dye-AA
      ozone.

PMID- 24117081
TI  - Biodegradation of 2-methylquinoline by Klebsiella pneumoniae TJ-A isolated from
      acclimated activated sludge.
AB  - Bacterial strain Klebsiella pneumoniae TJ-A, which was capable of utilizing 2
      methylquinoline as the sole carbon and energy source, was isolated from
      acclimated activated sludge under aerobic conditions. Effects of temperature and
      initial pH on the biodegradation of 2-methylquinoline by Klebsiella pneumoniae TJ
      A were investigated. The optimal temperature and initial pH were 30 degrees C and
      7.5, respectively. The degradation process was well described by the Haldane
      model. Then 1, 2, 3, 4-tetrahydro-2-methylquinoline, 4-ethyl-benzenamine and N
      butyl-benzenamine were metabolites detected during the degradation of 2
      methylquinoline. 2-Methylquinoline was initially hydroxylated at C-4 to form 2
      methyl-4-hydroxy-quinoline, and then to form 2-methyl-4-quinolinol as a result of
      tautomerism. Hydrogenation of heterocyclic ring between the position 2 and 3
      produced 2, 3-dihydro-2-methyl-4-quinolinol. The carbon-carbon bond between the
      position 2 and 3 in the heterocyclic ring cleaved and then formed 2-ethyl-N-ethyl
      benzenamine. Tautomerism might result in the formation of N-butyl-benzenamine.
      The 4-ethyl-benzenamine was produced as a result of losing one ethyl group from N
      butyl-benzenamine. The bacterial strain Klebsiella pneumoniae TJ-A was the
      priority species in the aerobic activated sludge responsible for the degradation
      of 2-methylquinoline. 

PMID- 24117082
TI  - Bacteria morphology and diversity of the combined autotrophic nitritation and
      sulfur-carbon three-dimensional-electrode denitrification process.
AB  - The bacterial morphology and diversity in the reactors of a combined autotrophic
      nitritation and sulfur-carbon three-dimensional-electrode denitrification
      (CANSCTED) process operating under steady-state conditions were investigated by
      scanning electron microscopy and partial 16S rDNA cloning and sequencing. The
      CANSCTED process consisted of two parts, i.e., the nitritation membrane
      bioreactor (NMBR) and the sulfur-carbon three-dimensional-electrode
      denitrification reactor (SCTED). When the influent NH4(+) concentration of NMBR
      ranged from 854 to 1086 mg N L(-1), with about 50% NH4(+) removal efficiency and
      NO2(-) accumulation rate, the spherical and spheroidal ammonia-oxidizing bacteria
      were predominant, with community successions of beta-Proteobacteria (60.0%),
      Bacteroidetes (28.3%) and Chloroflexi (11.7%). The NMBR effluent with 429~543 mg
      N L(-1) NH4(+) and 519~578 mg N L(-1) NO2(-) was continuously supplied to SCTED
      for sulfur denitrification, bioelectrochemical hydrogen denitrification, and
      anaerobic ammonium oxidation. The predominant bacterial community successions
      were beta-Proteobacteria (78.3%) and epsilon-Proteobacteria (21.7%). When the
      SCTED influent was supplied with only NO2(-) (412-525 mg N L(-1)) as nitrogen
      substrate, the predominant bacteria in SCTED were short-bacilliform and
      spheroidal denitrification bacteria, beta-Proteobacteria (82.0%), epsilon
      Proteobacteria (16.4%) and gamma-Proteobacteria (1.6%). Although the predominant
      bacterial communities were both beta-Proteobacteria and epsilon-Proteobacteria in
      SCTED, the species and quantity of each community varied with the change of SCTED
      influent composition, which indicated that the composition influence the
      bacterial morphology and diversity in SCTED.

PMID- 24117083
TI  - Nanocatalyst support of laser-induced photocatalytic degradation of MTBE.
AB  - This study was undertaken to develop a methodology suitable for the direct
      removal and degradation of methyl tertiary butyl ether (MTBE) in water using
      different nano-catalysts supported laser based photo-oxidation process. For this
      purpose, nano-structured WO3 catalyst was synthesized in our laboratory and its
      photocatalytic activity for the demineralization of MTBE in water was compared
      with different catalysts such as ZnO, TiO2, Fe2O3 and NiO using 355 nm laser
      radiations generated by the third harmonic of Nd: YAG laser. The effect of laser
      irradiation time, amount of catalysts and pH were also investigated for the
      optimization of MTBE removal process. For 60 min of laser exposure time, the
      overall percentage of MTBE degradation was found to be 93%, 89%, 82%, 80% and 71%
      for WO3, ZnO, Fe2O3, NiO and TiO2, respectively. In addition the photonic
      efficiencies of different nano-structured catalysts toward degradation of MTBE
      were estimated, and they were found to follow the trend of WO3 > ZnO > Fe2O3 >
      NiO > TiO2.

PMID- 24117084
TI  - Fate and behavior of ZnO- and Ag-engineered nanoparticles and a bacterial
      viability assessment in a simulated wastewater treatment plant.
AB  - The fate and behaviour assessment of ZnO- and Ag-engineered nanoparticles (ENPs)
      and bacterial viability in a simulated wastewater treatment plant (WWTP) fed with
      municipal wastewater was investigated through determination of ENPs stability at
      varying pH and continuous exposure of ENPs to wastewater, respectively. The ENPs
      were introduced to a 3-L bioreactor (simulated WWTP) with a hydraulic residence
      time (HRT) of 6 h at a dose rate of 0.83 mg/min for 240 h. The stability of the
      ENPs was found to be dependent on their dissolution and aggregation at different
      pH, where ZnO ENPs exhibited the highest dissolution at low pH compared to Ag
      ENPs. The results also showed that both ENPs had high affinity for the sewage
      sludge as they undergo aggregation under typical wastewater conditions. Results
      of effluent monitored daily showed mean COD removal efficiencies of 71 +/- 7% and
      74 +/- 8% for ZnO and Ag ENPs in test units, respectively. The treated effluent
      had low mean concentrations of Zn (1.39 +/- 0.54 mg/L) and Ag (0.12 +/- 0.06
      mg/L); however, elevated mean concentrations of Zn (54 +/- 39 mg/g dry sludge)
      and Ag (57 +/- 42 mg/g dry sludge) were found in the sludge - suggesting removal
      of the ENPs from the wastewater by biosorption and biosolid settling mechanisms.
      Using X-ray diffraction (XRD) and transmission electron microscopy (TEM), the
      mineral identities of ZnO and Ag ENPs in the sludge from the test units were
      found comparable to those of commercial ENPs, but larger due to agglomeration.
      The bacterial viability assessment after exposure to ENPs using the Live/Dead
      BacLight kit, although not quantitatively assessed, suggested high resilience of
      the bacteria useful for biodegradation of organic material in the simulated
      wastewater treatment system.

PMID- 24117085
TI  - Isolation and characterization of phenol utilizing bacteria from industrial
      effluent-contaminated soil and kinetic evaluation of their biodegradation
      potential.
AB  - Microbial degradation of phenol by pure bacterial species is a well-known
      approach towards alleviation of environmental pollution. In this study, five
      phenol-degrading bacterial species designated as CUPS-1 to CUPS-5 were isolated
      from the oil-effluent dumped sites of Haldia Industrial area of West Bengal,
      India. Detailed morphological, biochemical and molecular characterization
      identified CUPS-3 as a novel strain- Stenotrophomonas maltophilia (GU358076),
      while the others could be identified as Pseudomonas (CUPS-2, 5), Delftia (CUPS-1)
      and Micrococcus (CUPS-4) genera, respectively. Although all of these strains
      utilized phenol as their sole carbon source supporting growth, three among them,
      CUPS-2, CUPS-3 and CUPS-5 proved potential phenol degraders and hence used for
      further biodegradation studies. Degradation experiments were carried out for
      several initial phenol concentrations of 500 mg/L, 750 mg/L, 1000 mg/L, 1250 mg/L
      and 1500 mg/L. The novel strain, CUPS-3 could completely degrade 500 mg/L phenol
      within 48 h, with 0.0937/h substrate degradation rate and 16.34 mg/L/h substrate
      consumption rate. The strains degraded phenol via meta-cleavage pathway.
      Prediction of kinetic parameters of the biodegradation was accomplished Haldane
      model using the experimental data of degradation rate and phenol concentration as
      function of time.

PMID- 24117086
TI  - Mechanisms of interaction between polycyclic aromatic hydrocarbons and dissolved
      organic matters.
AB  - Binding of phenanthrene and fluorene to a number of humic and fulvic substances
      isolated from various sources as well as a commercially available humic acid, was
      investigated using a fluorescence quenching approach. The observed fluorescence
      quenching indicated by linear Stern-Volmer plots and high bimolecular quenching
      rate constant was induced by a static interaction process. A significant
      correlation of binding constants with aromaticity and polarity of dissolved
      organic matter (DOM) was observed. It is hypothesized that the binding of
      polycyclic aromatic hydrocarbons (PAHs) by DOM is due to both pi-pi interactions
      and hydrophobic interactions. In addition, energy transfer from PAHs to DOM
      occurs because of the significant overlap between the absorbance spectra of DOM
      and emission spectra of PAHs. Thus, dipole-dipole interaction may also play an
      important role in the binding mechanism between PAHs and DOM. 

PMID- 24117087
TI  - Biodegradation of glycerol using bacterial isolates from soil under aerobic
      conditions.
AB  - Glycerol, a non-biodegradable by-product during biodiesel production is a major
      concern to the emerging biodiesel industry. Many microbes in natural environments
      have the ability to utilize glycerol as a sole carbon and energy source. The
      focus of this study was to screen for microorganisms from soil, capable of
      glycerol utilization and its conversion to value added products such as ethanol
      and 1,3-propanediol (1,3-PDO). Twelve bacterial isolates were screened for
      glycerol utilization ability in shake flask fermentations using M9 media
      supplemented with analytical grade glycerol (30 g/L) at various pH values (6, 7
      and 8) and temperatures (30 degrees C, 35 degrees C and 40 degrees C). Among
      these, six bacterial isolates (SM1, SM3, SM4, SM5, SM7 and SM8) with high
      glycerol degradation efficiency (>80%) were selected for further analysis.
      Highest level of 1,3-PDO production (15 g/L) was observed with isolate SM7 at pH
      7 and 30 degrees C, while superior ethanol production (14 g/L) was achieved by
      isolate SM9 at pH 8 and 35 degrees C, at a glycerol concentration of 30 g/L. The
      selected strains were further evaluated for their bioconversion efficiency at
      elevated glycerol concentrations (50-110 g/L). Maximum 1,3-PDO production (46 g/L
      and 35 g/L) was achieved at a glycerol concentration of 70 g/L by isolates SM4
      and SM7 respectively, with high glycerol degradation efficiency (>90). Three
      isolates (SM4, SM5 and SM7) also showed greater glycerol tolerance (up to 110
      g/L). The isolates SM4 and SM7 were identified as Klebsiella pneumoniae and SM5
      as Enterobacter aerogenes by 16S rDNA analysis. These novel isolates with greater
      glycerol tolerance could be used for the biodegradation of glycerol waste
      generated from the biodiesel industry into value-added commercial products.

PMID- 24117088
TI  - Comparison of bioleaching of heavy metals from municipal sludge using indigenous
      sulfur and iron-oxidizing microorganisms: continuous stirred tank reactor
      studies.
AB  - A comparative study was undertaken using indigenous sulfur-oxidizing
      microorganisms and iron-oxidizing microorganisms in separate 12 litre continuous
      stirred tank reactors (CSTRs) for solubilization of heavy metals from
      anaerobically digested sewage sludge. The CSTRs were operated at hydraulic
      retention times (HRTs) ranging from 4 to 10 days using sewage sludge feed having
      near neutral pH. The pH, oxidation-reduction potential (ORP) and solubilization
      efficiency of metals were found to be highly dependent on HRT and an increase in
      HRT led to higher solubilization of metals in both the CSTRs. In both the CSTRs,
      the CSTR operated with sulfur-oxidizing microorganisms at an HRT of 8 days was
      found to be optimum in solubilizing 58% Cu, 52% Ni, 72% Zn and 43% Cu from the
      sludge. The nutrient value, nitrogen and phosphorus of bioleached sludge was also
      conserved (<20% loss) at 8 days HRT. The metals fractionation study conducted
      using BCR sequential extraction procedure suggested that most of the metals
      remaining in the bioleached sludge were in the more stable fractions (F3 and F4)
      and, therefore, can be safely apply as a fertilizer on land.

PMID- 24117089
TI  - Infrared wave analysis after hydrodynamic and acoustic cavitation as effective
      method of confirming sewage sludge destruction.
AB  - The efficiency of disintegration of sewage sludge cells microorganisms were
      characterized using biochemical parameters such as COD, phosphate, ammonium
      nitrogen and proteins. The investigated process was additionally assessed using
      the coefficient DD (Degree of Disintegration). It has been demonstrated that a 30
      min of hydrodynamic and ultrasonic disintegration causes the soluble COD value
      increased about 300 mg /L and 190 mg /L (average), while the degree of
      disintegration reached 24% and 21%, respectively. The efficiency of sewage sludge
      hydrodynamic and ultrasonic disintegration was confirmed by increased release of
      phosphate (V) (from 4 to 54 mg PO4(3-) /L and to 50 mg PO4(3-) /L, respectively),
      ammonium nitrogen (from 1.5 to 4 mg N-NH4(+) /L and to 3.5 mg N-NH4(+) /L,
      respectively) and proteins (from 5 to 70 mg/L and to 60 mg/L, respectively). The
      effectiveness of surplus activated sludge disintegration was tested in the
      infrared spectrum. Changes in absorbance at the specified wavelength attest to a
      release of i.e., amines, amino acids, amide groups (proteins), phosphates,
      ammonium salts of carboxylic acid, etc. during disintegration time. Revealing
      these chemical groups in over-sludge liquids attests to a destructive influence
      of hydrodynamic and ultrasonic cavitation on activated sludge microorganisms and
      effective cells lysis.

PMID- 24117090
TI  - Low-cost field test kits for arsenic detection in water.
AB  - Arsenic, a common contaminant of groundwater, affects human health adversely.
      According to the World Health Organization (WHO), the maximum recommended
      contamination level of arsenic in drinking water is 10 MUg/L. The purpose of this
      research was to develop user-friendly kits for detection of arsenic to measure at
      least up to 10 MUg/L in drinking water, so that a preventive measure could be
      taken. Two different kits for detection of total arsenic in water are reported
      here. First, the arsenic in drinking water was converted to arsine gas by a
      strong reducing agent. The arsine produced was then detected by paper strips via
      generation of color due to reaction with either mercuric bromide (KIT-1) or
      silver nitrate (KIT-2). These were previously immobilized on the detector strip.
      The first one gave a yellow color and the second one grey. Both of these kits
      could detect arsenic contamination within a range of 10 MUg/L-250 MUg/L. The
      detection time for both the kits was only 7 min. The kits exhibited excellent
      performance compared to other kits available in the market with respect to
      detection time, ease of operation, cost and could be easily handled by a layman.
      The field trials with these kits gave very satisfactory results. A study on
      interference revealed that these kits could be used in the presence of 24 common
      ions present in the arsenic contaminated water. Though the kits were meant for
      qualitative assay, the results with unknown concentrations of real samples, when
      compared with atomic absorption spectrophotometer (AAS) were in good agreement as
      revealed by the t-test.

PMID- 24117091
TI  - Picoplankton dynamics and picoeukaryote diversity in a hyper-eutrophic
      subtropical lagoon.
AB  - Picoplankton (cells with a diameter of 0.2-3.0 MUm) is the dominant contributor
      to both primary production and biomass in the ocean. Most of the previous studies
      on picoplankton have been conducted in the oligotrophic open sea with few in the
      eutrophic area. In this study, we investigated the dynamics of different groups
      of picoplankton and the diversity of picoeukaryote (based on 18S rDNA) in a hyper
      eutrophic marine coastal lagoon. The results indicated that temperature and
      phosphate concentration were most responsible for the dynamics of different
      picoplankton groups. Examination of 135 clones revealed 27 different Denaturing
      Gradient Gel Electrophoresis (DGGE) patterns. At least 7 high-level taxonomic
      groups of picoeukaryote were recorded. The picoeukaryotic diversities included
      Alveolates, Stramenopiles, Haptophyceae, and Viridiplantae, with Stramenopiles
      being the most diverse group. Overall the results of this study indicated that
      picoplankton diversity was low relative to studies conducted in more oligotrophic
      waters.

PMID- 24117092
TI  - Synthesis, characterization and photocatalytic activity of Al2O3-TiO2 based
      composites.
AB  - The synthesis, characterization and photocatalytic performance of non-traditional
      Al2O3-TiO2-based photocatalysts is reported. Al2O3-TiO2 support was loaded with
      various fractions of CuO and ZrO2. A sound agreement was observed between the
      bandgaps of synthesized powders measured by UV-Visible diffuse reflectance
      spectroscopy (DRS) in the solid phase and UV-Visible spectroscopy in the aqueous
      medium. X-ray diffraction (XRD) analysis revealed the composite nature of the
      catalysts with the retention of individual identity of each component. The
      average crystallite size of the individual component was found to be in the range
      of 20 to 40 nm. Scanning electron microscopy (SEM) analysis authenticated the
      presence of CuO and ZrO2 at the surface of Al2O3-TiO2 support, while Rutherford
      Back Scattering Spectroscopy (RBS) confirmed the quantity of the modifiers as per
      theoretical calculations. The composites showed an enhanced photocatalytic
      activity in sunlight compared to Al2O3-TiO2 for the degradation of dyes. Efforts
      were made to elucidate the enhanced sunlight response of the synthesized
      composite catalysts compared to Al2O3-TiO2. As monitored by ion chromatography
      (IC), the synthesized photocatalysts completely mineralized the dyes leaving
      behind inorganic ions in solution. The kinetics of photocatalytic degradation of
      dyes was evaluated for optimum correlation with the existing models. The
      stability of the photocatalysts against the photo-corrosion was monitored by
      analyzing the samples for respective metals in solution after sunlight exposure.
      Supplemental materials are available for this article. Go to the publisher's
      online edition of the Journal of Environmental Science and Health, Part A, to
      view the supplemental file.

PMID- 24117093
TI  - Unanswered questions in headache: so what is photophobia, anyway?

PMID- 24117094
TI  - Blueberry (Vaccinium virgatum) leaf extracts protect against Abeta-induced
      cytotoxicity and cognitive impairment.
AB  - The ethylacetate (EtOAc) fraction of blueberry leaf extract was investigated to
      examine the in vivo antiamnesic effects against amyloid beta protein (Abeta)
      induced learning and memory deficit. The fraction showed the highest antioxidant
      activities, and the generation of intracellular reactive oxygen species was
      significantly decreased. Cell viability assays revealed the in vitro
      cytoprotective effects of the fraction, and the cytoplasmic lactate dehydrogenase
      release into the medium was dose-dependently inhibited. In addition, a
      chlorogenic acid was identified as a predominant phenolic compound by high
      performance liquid chromatography analysis. Antiamnesic effects were evaluated by
      using in vivo the Y-maze and passive avoidance tests, and preadministration of
      the fraction attenuated Abeta-induced memory impairment in both in vivo
      experiments. Acetylcholinesterase prepared from mice brain was inhibited by the
      fraction, and malondialdehyde generation in the brain homogenate was also
      decreased. These findings suggest that the EtOAc fraction of blueberry leaf
      extract could possess a wide range of physiological effects against
      neurodegenerative diseases.

PMID- 24117095
TI  - Phytochemical linarin enriched in the flower of Chrysanthemum indicum inhibits
      proliferation of A549 human alveolar basal epithelial cells through suppression
      of the Akt-dependent signaling pathway.
AB  - In this study, we report the anti-proliferative effect and molecular mechanism of
      Chrysanthemum indicum (C. indicum) on A549 human alveolar basal epithelial cells.
      We also analyzed the changes in C. indicum component profiles due to
      modifications of predrying process, flower size, and extraction method. Among the
      varieties of modifications tested, high-temperature heat dry (HTD) of small
      flower biotype followed by the methanolic extraction resulted in the strongest
      anti-proliferative activity of C. indicum extract in A549 cells. High-performance
      liquid chromatography of C. indicum revealed that the levels of acacetin 7-O
      rutinoside (linarin) are markedly increased by heat treatment, especially HTD.
      Finally, we showed that linarin-mediated inhibition of cell proliferation is
      associated with suppression of Akt activation and induction of cyclin-dependent
      kinase inhibitor p27(Kip1) as evidenced by cell cycle analysis and treatment with
      LY294002, an inhibitor of phosphatidylinositol 3-kinase/Akt pathway. Taken
      together, these findings suggest the need for further development and evaluation
      of linarin from C. indicum for the treatment and prevention of lung cancer.

PMID- 24117096
TI  - Doubly-robust estimators of treatment-specific survival distributions in
      observational studies with stratified sampling.
AB  - Observational studies are frequently conducted to compare the effects of two
      treatments on survival. For such studies we must be concerned about confounding;
      that is, there are covariates that affect both the treatment assignment and the
      survival distribution. With confounding the usual treatment-specific Kaplan-Meier
      estimator might be a biased estimator of the underlying treatment-specific
      survival distribution. This article has two aims. In the first aim we use
      semiparametric theory to derive a doubly robust estimator of the treatment
      specific survival distribution in cases where it is believed that all the
      potential confounders are captured. In cases where not all potential confounders
      have been captured one may conduct a substudy using a stratified sampling scheme
      to capture additional covariates that may account for confounding. The second aim
      is to derive a doubly-robust estimator for the treatment-specific survival
      distributions and its variance estimator with such a stratified sampling scheme.
      Simulation studies are conducted to show consistency and double robustness. These
      estimators are then applied to the data from the ASCERT study that motivated this
      research.

PMID- 24117097
TI  - Headspace-free setup of in vitro bioassays for the evaluation of volatile
      disinfection by-products.
AB  - The conventional setup of in vitro bioassays in microplates does not prevent the
      loss of volatile compounds, which hampers the toxicological characterization of
      waterborne volatile disinfection by-products (DBPs). To minimize the loss of
      volatile test chemicals, we adapted four in vitro bioassays to a headspace-free
      setup using eight volatile organic compounds (four trihalomethanes, 1,1
      dichloroethene, bromoethane, and two haloacetonitriles) that cover a wide range
      of air-water partition coefficients. The nominal effect concentrations of the
      test chemicals decreased by up to three orders of magnitude when the conventional
      setup was changed to a headspace-free setup for the bacterial cytotoxicity assay
      using bioluminescence inhibition of Vibrio fischeri. The increase of apparent
      sensitivity correlated significantly with the air-water partition coefficient.
      Purge and trap GC/MS analysis revealed a reduced loss of dosed volatile compounds
      in the headspace free setup (78-130% of nominal concentration) compared to a
      substantial loss in the conventional set up (2-13% of the nominal concentration).
      The experimental effect concentrations converged with the headspace-free setup to
      the effect concentrations predicted by a QSAR model, confirming the suitability
      of the headspace-free approach to minimize the loss of volatile test chemicals.
      The analogue headspace-free design of the bacterial bioassays for genotoxicity
      (umuC assay) and mutagenicity (Ames fluctuation assay) increased the number of
      compounds detected as genotoxic or mutagenic from one to four and zero to two,
      respectively. In a bioassay with a mammalian cell line applied for detecting the
      induction of the Nrf-2-mediated oxidative stress response (AREc32 assay), the
      headspace-free setup improved the apparent sensitivity by less than one order of
      magnitude, presumably due to the retaining effect of the serum components in the
      medium, which is also reflected in the reduced aqueous concentrations of
      compounds. This study highlights the importance of adapting bioanalytical test
      setups when volatile/semivolatile compounds are present in the sample to avoid
      the loss of chemicals and thus to avoid underestimating the toxicity of mixtures
      and complex environmental samples. 

PMID- 24117099
TI  - Copper deficiency anaemia.

PMID- 24117098
TI  - Resting state networks in temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is typically described as a neurologic disorder
      affecting a cerebral network comprising the hippocampus proper and several
      anatomically related extrahippocampal regions. A new level of complexity was
      recently added to the study of this disorder by the evidence that TLE also
      appears to chronically alter the activity of several brain-wide neural networks
      involved in the control of higher order brain functions and not traditionally
      linked to epilepsy. Recently developed brain imaging techniques such as
      functional magnetic resonance imaging (fMRI) analysis of resting state
      connectivity, have greatly contributed to these observations by allowing the
      precise characterization of several brain networks with distinct functional
      signatures in the resting brain, and therefore also known as "resting state
      networks." These significant advances in imaging represent an opportunity to
      investigate the still elusive origins of the disabling cognitive and psychiatric
      manifestations of TLE, and could have important implications for its
      pathophysiology and, perhaps, its therapy. Herein we review recent studies in
      this field by focusing on resting state networks that have been implicated in the
      pathophysiology of psychiatric disorders and cognitive impairment in patients
      with epilepsy: the default mode network, the attention network, and the
      reward/emotion network. 

PMID- 24117100
TI  - Enzymatic synthesis of extra virgin olive oil based infant formula fat analogues
      containing ARA and DHA: one-stage and two-stage syntheses.
AB  - Structured lipids (SLs) with high palmitic acid content at the sn-2 position
      enriched with arachidonic acid (ARA) and docosahexaenoic acid (DHA) were produced
      using extra virgin olive oil, tripalmitin, ARA and DHA single cell oil free fatty
      acids. Four types of SLs were synthesized using immobilized lipases, Novozym 435
      and Lipozyme TL IM, based on one-stage (one-pot) and two-stage (sequential)
      syntheses. The SLs were characterized for fatty acid profile, triacylglycerol
      (TAG) molecular species, melting and crystallization profiles, tocopherols, and
      phenolic compounds. All the SLs had >50 mol % palmitic acid at the sn-2 position.
      The predominant TAGs in all SLs were PPO and OPO. The total tocopherol content of
      SL1-1, SL1-2, SL2-1, and SL2-2 were 70.46, 68.79, 79.64, and 79.31 MUg/g,
      respectively. SL1-2 had the highest melting completion (42.0  degrees C) and
      crystallization onset (27.6  degrees C) temperatures. All the SLs produced in
      this study may be suitable as infant formula fat analogues. 

PMID- 24117101
TI  - The true value of decreased delayed starts of the first case.

PMID- 24117102
TI  - Health promotion for patients with diabetes: health coaching or formal health
      education?
AB  - PURPOSE: The purpose of this study was to determine if a Health Coaching (HC)
      approach compared with formal health education (HE) resulted in better health
      outcomes among type II diabetes (T2DM) patients in improving glycaemic control
      and oral health, by use of clinical and subjective outcome measures. METHODS: The
      study is part of a prospective intervention among randomly selected T2DM patients
      (n = 186) in Istanbul, Turkey. The data analysed were clinical [glycated
      haemoglobin (HbA(1C)), clinical attachment loss (CAL)] and psychological measures
      [tooth-brushing self efficacy (TBSES)]. Data were collected initially and at the
      end of intervention. Participants were allocated randomly to HC (intervention) (n
      = 77) and HE (control) (n = 111) groups. RESULTS: At baseline, there was no
      statistical difference between HC and HE regarding clinical and psychological
      measures, (P > 0.05). At post-intervention the HC group had significantly lower
      HBA(1C) and CAL (reduction: 7%, 56%) than the HE group (reduction: HbA(1C) 0%;
      CAL 26%), (P <= 0.01). Similarly, HC group, compared with HE group, had better
      TBSES (increase: 61% vs. 25%) and stress (reduction: 16% vs. 1%), (P <= 0.01).
      Among high-risk group patients, the HC patients had significant improvements
      compared with the HE group (reduction: HbA(1C) 16% vs. 5%; CAL 63% vs. 18%;
      stress 39% vs. 2%; fold increase: TBSES 6.6 vs. 3.6) (P <= 0.01). CONCLUSIONS:
      The present findings may imply that HC has a significantly greater impact on
      better management of oral health and glycaemic control than HE. It is notable
      that the impact was more significant among high-risk group patients, thus HC may
      be recommended especially for high-risk group patients.

PMID- 24117103
TI  - Stroke in infancy: a convergence of causes.

PMID- 24117104
TI  - Causes of stillbirth at different gestational ages in singleton pregnancies.
AB  - OBJECTIVE: To compare causes of stillbirth in preterm and term pregnancies.
      DESIGN: Cohort study. SETTING: All delivery wards in Stockholm, 1998-2009.
      POPULATION: Stillbirths from singleton pregnancies of gestational age >=22(+0) (n
      = 1089) extracted from a web-based database including all stillbirths in the
      major Stockholm area since 1998. METHODS: The parents of the stillborns were all
      offered an extensive standardized investigation. The causes of death were
      assigned in a perinatal audit using the Stockholm classification of stillbirth.
      Singleton stillbirths were divided into preterm (gestational week 22(+0) -36(+6)
      ) and term/post-term (gestational week >=37(+0) ). The term/post-term group was
      subdivided into term (gestational week 37(+0) -40(+6) ) and post-term stillbirths
      (gestational week >=41(+0) ). MAIN OUTCOME MEASURE: Causes of stillbirth at
      different gestational ages. RESULTS: A higher proportion of placental abruption
      and preeclampsia/hypertension was seen in preterm stillbirths compared with
      term/post-term stillbirths, which instead had a higher proportion of umbilical
      cord complications and infection. Infection was more common in post-term than
      term stillbirths (46.5 vs. 19.8%, p < 0.001). CONCLUSION: Increased knowledge of
      causes of stillbirth in different gestational ages may be valuable in developing
      strategies for prevention of fetal death. The high proportion of infection in
      post-term stillbirths could be clinically important and warrants further studies.

PMID- 24117107
TI  - Self-assembly to function: design, synthesis, and broad spectrum antimicrobial
      properties of short hybrid E-vinylogous lipopeptides.
AB  - Nonribosomal E-vinylogous gamma-amino acids are widely present in many peptide
      natural products and have been exploited as inhibitors for serine and cysteine
      proteases. Here, we are reporting the broad spectrum antimicrobial properties and
      self-assembled nanostructures of various hybrid lipopeptides composed of 1:1
      alternating alpha- and E-vinylogous residues. Analysis of the results revealed
      that self-assembled nanostructures also play a significant role in the
      antimicrobial and hemolytic activities. In contrast to the alpha-peptide
      counterparts, vinylogous hybrid peptides displayed excellent antimicrobial
      properties against various bacterial and fungal strains. Peptides that adopted
      nanofiber structures displayed less hemolytic activity, while peptides that
      adopted nanoneedle structures displayed the highest hemolytic activity. 

PMID- 24117106
TI  - The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor
      and bradycardic responses to DOPA in the nucleus tractus solitarii.
AB  - BACKGROUND AND PURPOSE: L-DOPA is generally considered to alleviate the symptoms
      of Parkinson's disease by its conversion to dopamine. We have proposed that DOPA
      is itself a neurotransmitter in the CNS. However, specific receptors for DOPA
      have not been identified. Recently, the gene product of ocular albinism 1 (OA1)
      was found to exhibit DOPA-binding activity. Here, we have investigated whether
      OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS).
      EXPERIMENTAL APPROACH: We examined immunohistochemical expression of OA1 in the
      NTS, and the effects of DOPA microinjected into the depressor sites of NTS on
      blood pressure and heart rate in anaesthetized rats, with or without prior knock
      down of OA1 in the NTS, using shRNA against OA1. KEY RESULTS: Using a specific
      OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor
      sites of the NTS. OA1 expression in the NTS was markedly suppressed by
      microinjection into the NTS of adenovirus vectors carrying the relevant shRNA
      sequences against OA1. In animals treated with OA1 shRNA, depressor and
      bradycardic responses to DOPA, but not those to glutamate, microinjected into the
      NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a
      competitive antagonist against OA1, suppressed phenylephrine-induced bradycardic
      responses without affecting blood pressure responses. CONCLUSION AND
      IMPLICATIONS: OA1 acted as a functional receptor for DOPA in the NTS, mediating
      depressor and bradycardic responses. Our results add to the evidence for a
      central neurotransmitter role for DOPA, without conversion to dopamine.

PMID- 24117108
TI  - Dark and photo-conductivity in ordered array of nanocrystals.
AB  - A theory of photo- and dark-band conductivities in semiconductor supercrystals
      consisting of nanocrystals is developed by assuming scattering by structural
      defects in the supercrystals. A new proposed mechanism of photoexcitation, which
      is triggered by an efficient Auger ionization of charged nanocrystals, provides
      explanation for the measured photocurrent being 2-3 orders of magnitude larger
      than the dark current. For dark conductivity, the metal-insulator transitions and
      temperature dependence of mobility in the metal phase are considered. 

PMID- 24117105
TI  - Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven
      pathway.
AB  - The principal biological role of mitochondria is to supply energy to cells;
      although intriguingly, evolution has bestowed another essential function upon
      these cellular organelles: under physiological stress, mitochondria become the
      cornerstone of apoptotic cell death. Specifically, mitochondrial outer membrane
      permeabilization (MOMP) allows cell death factors such as cytochrome c to be
      released into the cytoplasm, thus inducing caspase activation and the eventual
      destruction of essential cellular components. Proteins of the B-cell lymphoma 2
      (BCL-2) family control the tightly regulated pathway that causes MOMP. The
      equilibrium between pro-survival and pro-apoptotic members of the BCL-2 family
      dictates the fate of cells, the homeostasis of organs and, by extension, the
      health of whole organisms. Dysregulation of this equilibrium is involved in a
      large number of diseases such as cancer, autoimmunity and neurodegenerative
      conditions. Modulating the activity of the BCL-2 family of proteins with small
      molecules or peptides is an attractive but challenging therapeutic goal. This
      review highlights the latest developments in this field and provides evidence
      that this strategy is likely to have a positive effect on the treatment of still
      poorly addressed medical conditions.

PMID- 24117109
TI  - Informed consent for exome sequencing in diagnostics: exploring first experiences
      and views of professionals and patients.
AB  - Next-generation sequencing is increasingly being chosen as a diagnostic tool for
      cases of expected genetic, but unresolved origin. The consequential increased
      need for decisions on disclosure of unsolicited findings poses a challenge for
      the informed consent procedure. This study explored the first experiences with,
      and needs for, the informed consent procedure in diagnostic exome sequencing,
      with the stakeholders involved. Semi-structured interviews were conducted with 11
      professional experts and one professional gave a written response. Furthermore,
      the counseling process was observed in three cases where exome sequencing was
      offered, followed by interviews with the patient (representative) and the genetic
      counselor. The respondents not only preferred an opt-out for unsolicited findings
      but also identified many challenges and therefore more experiences with exome
      sequencing was considered needed. Context-dependent decision-making was observed
      and an Advisory Board for unsolicited findings was considered helpful while
      doubts were raised about the feasibility and the possibility of undermining
      patients' autonomy. Finally, respondents brought up the complexity of information
      provision, and division of responsibilities between clinicians and the lab. These
      challenges and needs, raised by stakeholders involved, provide more insight in
      the next steps needed for an optimal informed consent procedure for exome
      sequencing in diagnostics. 

PMID- 24117110
TI  - Physiological modulation approaches to improve cancer chemotherapy : a review.
AB  - The success of anticancer therapy is limited due to the resistance caused by
      tumor cells to cytotoxic agents, which interfere with the effectiveness of
      various chemotherapeutic agents. Several mechanisms for decreased effectiveness
      of anti-cancer drugs have been examined however the most widely studied mechanism
      is the efflux of cytotoxic drugs from the cell due to P-gp overexpression.
      However, the role of P-gp inhibitors in improving chemotherapy is limited due to
      the existence of other mechanisms of resistance such as activation of glutathione
      mediated detoxification, blockade of DNA repair, apoptotic pathways, TK signaling
      pathways and altered tumor microenvironment. Alternative strategies to overcome
      factors responsible for reduced efficacy of cancer therapy have also been
      considered such as inhibition of the detoxification system like glutathione,
      targeting Tks and DNA repair pathways, combination of angiogenic inhibitors, RNAi
      mediated inhibition of targeted genes etc. Additionally, preventing the onset of
      resistance can be targeted via siRNA strategy and nanoparticle strategy. In this
      review, we describe detailed mechanisms involved in decreasing effectiveness of
      anticancer drugs as well as the strategies used to modulate these mechanisms for
      effective cancer treatment. 

PMID- 24117112
TI  - Electronic excitations in Fischer-type Cr and W aminocarbene complexes: a
      combined ab initio and experimental study.
AB  - The influence of the substitution on the carbene ligand in the series of Fischer
      type Cr and W aminocarbene complexes was studied experimentally by UV-vis
      spectroscopy and theoretically by comparative ab initio SA-CASSCF/MS-CASPT2 and
      TD-DFT methods. Both calculations interpreted the experimental UV-vis spectra and
      their variations caused by substitution effects well. TD-DFT analysis of
      individual transitions using electron density redistributions indicated that the
      variation of the absorption spectra due to substitution is accompanied by a
      change in the character of the low-lying excited states participating in the
      visible bands. Correlated MS-CASPT2 calculations confirmed the TD-DFT assignments
      of the lowest-lying transitions in the visible region almost quantitatively. 

PMID- 24117111
TI  - Neuroprotective effects of argatroban and C5a receptor antagonist (PMX53)
      following intracerebral haemorrhage.
AB  - Intracerebral haemorrhage (ICH) is a subtype of stroke that associated with
      neurological dysfunction and inflammation, which may be ameliorated by a
      neuroprotective strategy targeting the complement cascade. The protective effect
      of C5a-receptor antagonist (PMX53) solely and in combination with thrombin
      antagonist (argatroban) was investigated in the ICH mouse model, respectively.
      Adult male C57BL/6J wild-type (WT) mice and C3(-/-) mice were randomized to
      receive PMX53/argatroban 1, 3 and 5 days after ICH. A double injection technique
      was used to infuse 25 MUl of autologous whole blood into the right striatum. Mice
      in the sham group received only needle insertion. Brain water content and mRNA of
      inflammatory factors were measured on the first, third and fifth days after ICH,
      respectively. Neurological dysfunction was assessed using a 28-point neurological
      scoring system in the three cohorts, namely, on days 1, 3 and 5 following ICH.
      Animals treated with PMX53/argatroban demonstrated significant improvements in
      neurological function and fewer neurological apoptosis detected by TUNEL
      [terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling]
      and betaIII-tubulin dual-staining compared with vehicle-treated animals. Compared
      with sham-treated mice, the brain water content in argatroban/PMX53-treated mice
      was decreased significantly in both the ipsilateral cortex and ipsilateral
      striatum. Administration of PMX53/argatroban provided a synergistic
      neuroprotective effect via reducing inflammatory factors and brain oedema,
      leading to improvements in neurofunctional outcome. The results of this study
      indicated that simultaneous blockade of the thrombin and C5a receptors represent
      a promising neuroprotective strategy in haemorrhagic stroke. 

PMID- 24117113
TI  - Stiripentol exhibits higher anticonvulsant properties in the immature than in the
      mature rat brain.
AB  - PURPOSE: After the first positive experimental data in rodents in the early 1970s
      demonstrating the anticonvulsant effect of stiripentol (STP), in vitro studies
      showed that STP acts directly on gamma-aminobutyric acid A (GABAA ) receptors.
      Chloride influx is higher when these receptors contain an alpha3 subunit, leading
      to the hypothesis that STP might exhibit higher efficacy in the immature brain.
      METHODS: We explored this issue by studying the efficacy of STP in P21 and P75
      rats using the pentylenetetrazol model of acute seizures or the lithium
      pilocarpine status epilepticus model. P21 and adult rats received vehicle, 150,
      250, or 350 mg/kg of STP, i.p., 1 h before evaluating the anticonvulsant. We also
      studied the blood and brain levels of STP as well as the expression and the
      messenger RNA (mRNA) levels of the alpha3 subunit of the GABAA receptors at both
      ages. KEYS FINDINGS: STP exhibited anticonvulsant properties in both models at
      both ages, but STP was more effective in P21 than in P75 rats. This was shown by
      the significant suppression of seizure or status epilepticus occurrence in P21
      with 350 mg/kg STP, whereas the same dose had no significant effect at P75. The
      blood level, brain level, and blood/brain ratio of STP did not explain these
      differences between the two age groups. Moreover, the higher anticonvulsant
      properties in the immature brain were not explained by the mRNA level or protein
      expression of the GABAA alpha3 subunit at either age. SIGNIFICANCE: Stiripentol
      exhibits higher anticonvulsant properties in the immature than in the mature
      brain. These findings require further investigation because it might lead to new
      clinical developments.

PMID- 24117114
TI  - Inhalational anesthetic sevoflurane rescues retina function in Alzheimer's
      disease transgenic Drosophila.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease that is a great public
      health problem worldwide. The cause and mechanism of AD are not well understood.
      Inhalational anesthetics have been suggested to induce neurotoxicity, leading to
      memory deficits and the progression of AD. However, recent data have shown that
      inhalational anesthetics may protect against neurotoxicity and are not associated
      with an increased risk of AD. We used a Drosophila model to directly investigate
      the neurologic effects of the inhalational anesthetic sevoflurane on AD. Five- to
      six-day-old control and AD-transgenic flies were exposed to 2.1% or 3%
      sevoflurane 4 and 16 times for 1 hour each time. Electroretinograms (ERG),
      retinal immunohistochemistry, climbing ability, and survival were analyzed after
      sevoflurane treatment. The data were evaluated using Student's t-test or a one
      way ANOVA with a supplementary Fisher's LSD (Least Significant Difference) test.
      Statistical significance was set at p<0.05. The DeltaERG, climbing ability, and
      survival were lower in AD-transgenic flies. Exposure to 2.1% sevoflurane 4 and 16
      times and to 3% sevoflurane 16 times rescued the DeltaERG in AD-transgenic flies.
      Sevoflurane exposure did not attenuate the climbing ability or survival of
      control and AD-transgenic flies. The inhalational anesthetic sevoflurane might
      not have exerted neurotoxic effects on control and AD-transgenic flies; in fact,
      sevoflurane might confer selective neuroprotection on the retinal function of AD
      transgenic flies. These results suggest the need for future studies to determine
      the potential effects of anesthetics on AD-associated neuroprotection or
      neurotoxicity.

PMID- 24117115
TI  - Tryptamine induces axonopathy and mitochondriopathy mimicking neurodegenerative
      diseases via tryptophanyl-tRNA deficiency.
AB  - Neurodegeneration is induced by tryptamine, a human diet constituent, which
      easily crosses the blood/brain barrier. Tryptamine neurotoxicity, caused by
      tryptophanyl-tRNA synthetase (TrpRS) inhibition and downregulation leads to
      tryptophanyl-tRNA deficiency and synthesis of aberrant proteins. We identified
      axonal defects in hippocampus of tryptamine- treated mice similar to those
      observed in human brain of patients with Alzheimer's disease, multiple sclerosis
      and epilepsy using anti-TrpRS site-directed antibodies. The axonal defects are
      characterized by swellings that accumulate abnormal amounts of helical filaments
      and amyloid. Tryptamine produced a decreased density of somatic mitochondria
      concomitant with neuronal loss in mouse hippocampus. In addition, tryptamine
      evoked accumulation and clustering of small mitochondria in mouse hippocampus
      causing axonal swellings. Similarly, mitochondrial fission, fusion and clustering
      were revealed in human neuronal cells after tryptamine administration. Moreover
      the tryptamine-induced mitochondrial neuropathology includes electron-dense
      deposits comprising helical fibrils, cristae disruption, cristolysis,
      mitochondrial swelling and mitochondria-derived vesicles. TrpRS+ helical
      filamentous tangles formed in both neuronal and kidney cells following tryptamine
      treatment suggest a tryptamine broad cytotoxic repertoire in damaging vital
      organs. Tryptamine elicited vesicularization of inner and outer mitochondrial
      membranes, axonal and cell membranes. Ultrastructurally, fragmentation of swollen
      degenerated mitochondria, small mitochondria clustering and neurofibrillary
      tangles are associated with axonal membrane protrusions attributed as neuritic
      swellings at a lower magnification. TrpRS+ axonal swellings associated with
      neuropathology of patients and tryptamine-treated human cells suggest that under
      toxic concentrations, tryptamine is implicated as a causative agent in
      neurodegeneration resembling that defining a number of human diseases. 

PMID- 24117116
TI  - Plasma clusterin levels and the rs11136000 genotype in individuals with mild
      cognitive impairment and Alzheimer's disease.
AB  - AIM: Substantial evidence links atherosclerosis and Alzheimer's disease (AD).
      Apolipoproteins, such as apolipoprotein E, have a causal relationship with both
      diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin
      (apolipoprotein J), is also associated with increased AD risk. The aim of this
      study was to investigate the relationship between plasma clusterin and the
      rs11136000 genotype in mild cognitive impairment (MCI) and AD. METHODS: Plasma
      and DNA samples were collected from control, MCI and AD subjects (n=142, 111,
      154, respectively). Plasma clusterin was determined by ELISA and DNA samples were
      genotyped for rs11136000 by TaqMan assay. RESULTS: Plasma clusterin levels were
      higher in MCI and AD subjects vs. controls (222.3 +/- 61.3 and 193.6 +/- 58.2 vs.
      178.6 +/- 52.3 MUg/ml, respectively; p<0.001 for both comparisons), and in MCI
      vs. AD (p<0.05). Plasma clusterin was not influenced by genotype in the MCI and
      AD subjects, although in control subjects plasma clusterin was lower in the TT
      vs. TC genotypes (157.6 +/- 53.4 vs. 188.6 +/- 30.5 MUg/ml; p<0.05). CONCLUSION:
      This study examined control, MCI and AD subjects, identifying for the first time
      that plasma clusterin levels were influenced, not only by the presence of AD, but
      also the transitional stage of MCI, while rs11136000 genotype only influenced
      plasma clusterin levels in the control group. The increase in plasma clusterin in
      MCI and AD subjects may occur in response to the disease process and would be
      predicted to increase binding capacity for amyloid-beta peptides in plasma,
      enhancing their removal from the brain.

PMID- 24117117
TI  - Correlations between cerebellar and brain volumes, cognitive impairments, ApoE
      levels, and APOE genotypes in patients with AD and MCI.
AB  - Due to the increasing incidence of Alzheimer's disease (AD), many studies have
      aimed to improve its diagnosis. Particular attention has been focused on
      measuring volumes of brain structures. Only few studies have investigated whether
      the cerebellar volume changes with the stage of dementia. It is controversial
      whether the serum apolipoprotein E (ApoE) level is an appropriate AD marker. This
      study was designed to clarify the significance of both cerebellar volume
      measurements and ApoE level measurements as markers of neurodegenerative changes.
      This study included 55 subjects with AD, 30 subjects with mild cognitive
      impairments (MCI), and a control group with 30 subjects. We measured the brain,
      cerebellum, and brain stem volumes with magnetic resonance imaging (MRI). We
      determined serum ApoE levels, APOE genotypes, and neuropsychological test scores.
      In the control group, we found that ApoE levels were significantly higher for
      subjects with the APOE 2/3 genotype than those with the 4/4 genotype. This
      finding may indicate that ApoE plays a protective role against AD development in
      subjects with the APOE 2/3 genotype. ApoE levels were not significantly different
      in patients with AD and MCI. No correlations were found between serum ApoE levels
      and Mini-Mental State Examination (MMSE) scores or the volumes of brain
      structures. This study could not confirm the appropriateness of the cerebellum
      volume as an early AD marker. Correlations were found between cerebellar volume,
      brain volume, and the MMSE scores.

PMID- 24117118
TI  - Reliability of the Alzheimer's disease assessment scale (ADAS-Cog) in
      longitudinal studies.
AB  - BACKGROUND: Considering the scarcity of longitudinal assessments of reliability,
      there is need for a more precise understanding of cognitive decline in
      Alzheimer's Disease (AD). The primary goal was to assess longitudinal changes in
      inter-rater reliability, test retest reliability and internal consistency of
      scores of the ADAS-Cog. METHODS: 2,618 AD subjects were enrolled in seven
      randomized, double-blind, placebo-controlled, multicenter-trials from 1986 to
      2009. Reliability, internal-consistency and cross-sectional analysis of ADAS-Cog
      and MMSE across seven visits were examined. RESULTS: Intra-class correlation
      (ICC) for ADAS-Cog was moderate to high supporting their reliability. Absolute
      Agreement ICCs 0.392 (Visit-7) to 0.806 (Visit-2) showed a progressive decrease
      in correlations across time. Item analysis revealed a decrease in item
      correlations, with the lowest correlations for Visit 7 for Commands (ICC=0.148),
      Comprehension (ICC=0.092), Spoken Language (ICC=0.044). DISCUSSION: Suitable
      assessment of AD treatments is maintained through accurate measurement of
      clinically significant outcomes. Targeted rater education ADAS-Cog items over
      time can improve ability to administer and score the scale.

PMID- 24117119
TI  - Pupil response biomarkers for early detection and monitoring of Alzheimer's
      disease.
AB  - INTRODUCTION: A screening process that could provide early and accurate diagnosis
      or prognosis for Alzheimer's disease (AD) would enable earlier intervention, and
      enable current and future treatments to be more effective. Ocular pathology and
      changes to vision and ocular function are being investigated for early detection
      and monitoring of AD. OBJECTIVE: To explore the relationship between pupil flash
      response (PFR) parameters, AD and brain amyloid plaque burden. METHODS: Nineteen
      AD and seventy healthy control (HC) participants were recruited from the
      Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. The
      potential correlations between PFR parameters and 1) AD and 2) brain amyloid
      plaque burden in the HC group (as a pre-clinical feature of AD), were
      investigated in this study. RESULTS: Our results demonstrate statistically
      significant relationships between PFR parameters, neocortical plaque burden and
      AD. A logistical model combining PFR parameters provided AD-classification
      performance with sensitivity 84.1%, specificity 78.3% and area under the curve
      89.6%. Furthermore, some of the AD specific PFR parameters were also associated
      with neocortical plaque burden in pre-clinical AD. CONCLUSIONS: These PFR changes
      show potential as an adjunct for noninvasive, cost-effective screening for pre
      clinical AD.

PMID- 24117120
TI  - Serum beta-amyloid peptide levels spike in the early stage of Alzheimer-like
      plaque pathology in an APP/PS1 double transgenic mouse model.
AB  - Serum levels of beta-amyloid (Abeta) peptides may represent an early biomarker in
      the diagnosis of Alzheimer's disease (AD). In the present study, we investigated
      the temporal kinetic changes in the levels of serum Abeta 1-42 and 40 in an
      amyloid precursor protein (APP)/presenilin (PS)1 double transgenic mouse model of
      AD. Serum Abeta peptide levels in 2-, 3-, 6-, 9- and 18-month old, and liver
      Abeta 1-40 level in 6-month old mice were measured using enzyme-linked
      immunosorbent assay (ELISA) kits. Results revealed that serum Abeta levels peaked
      in 3-month old transgenic mice, and the Abeta level in non-transgenic and
      transgenic mice is comparable in liver. Compared to the 6-month old transgenic
      mice, Congo red staining showed that the 3-month old transgenic mice had minimum
      brain Abeta plaques, corresponding to the early stage of Alzheimer-like plaque
      pathology, and confocal microscope images showed that the deposition of Abeta in
      their cerebral vessels was minimal. Furthermore, results of the water maze test,
      showed that memory was normal for the 3- month old transgenic mice when compared
      to age-matched non-transgenic mice. These results suggest that serum Abeta
      peptide levels may be peaked during the early stage of AD. Monitoring serum Abeta
      peptide levels in the potential AD population may provide an early diagnosis of
      AD prior to the appearance of clinical symptoms. 

PMID- 24117121
TI  - Sporadic hemiplegic migraine with permanent neurological deficits.
AB  - By definition, the neurologic impairments of hemiplegic migraine are reversible.
      However, a few cases of permanent neurologic deficits associated with hemiplegic
      migraine have been reported. Herein, we present the case of a patient with
      permanent impairments because of hemiplegic migraine despite normalization of
      associated brain magnetic resonance imaging abnormalities. Cases like these
      suggest the need to consider aggressive prophylactic therapy for patients with
      recurrent hemiplegic migraine attacks. 

PMID- 24117122
TI  - Efficacy and safety of bupivacaine versus lidocaine in dental treatments: a meta
      analysis of randomised controlled trials.
AB  - The objective of this study was to assess the efficacy and safety of bupivacaine
      compared with lidocaine in local anaesthesia in dental treatment. Medline,
      Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical
      Literature Database, China National Knowledge Infrastructure, and the World
      Health Organisation (WHO) International Clinical Trials Registry Platform were
      searched electronically. Relevant journals and references of studies included
      were hand-searched for randomised controlled trials comparing bupivacaine with
      lidocaine in terms of efficacy and safety. Sixteen studies were included, of
      which nine had low, six had moderate and one had high risk of bias. In comparison
      with 2% lidocaine plus 1:100,000 adrenaline, 0.5% bupivacaine plus 1:200,000
      adrenaline showed a higher success rate in inflamed pulp (P = 0.03) but a lower
      success rate in vital pulp (P < 0.00001), a lower percentage of patients using
      postoperative analgesics (P < 0.00001), a longer onset times of pulpal
      anaesthesia and a longer duration of pulpal anaesthesia (P < 0.00001). In
      comparison with 2% lidocaine plus 1:80,000 adrenaline, 0.75% bupivacaine plus
      1:200,000 adrenaline had same level of success rate (P = 0.29), and was better in
      postoperative pain control (P = 0.001) while 0.75% levobupivacaine had same level
      of postoperative pain control (P = 0.16); 0.5% levobupivacaine had higher success
      rate (P = 0.04) and was better in postoperative pain control (P = 0.001) than 2%
      lidocaine. There was no statistically significance in adverse events between two
      groups. Given the efficacy and safety, the bupivacaine group is better than the
      lidocaine group in dental operations that take a relatively long time, especially
      in endodontic treatments or where there is a need for postoperative pain
      management.

PMID- 24117123
TI  - Testing the reliability of Grade, Roughness and Breathiness scores by means of
      synthetic speech stimuli.
AB  - This article describes a synthesizer of disordered voices and reports a test of
      the reliability of Grade, Roughness, and Breathiness scores assigned to synthetic
      stimuli by eight expert listeners in two sessions. Speech stimuli [a], [i], [u],
      [ai], and [ia] were synthesized with three values of vocal frequency and four
      levels of vocal jitter and pulsatile additive noise each. The agreement and
      correlation of scores assigned by the same rater in different sessions, or by
      different raters in the same session, accord with published data. Only a small
      part of the variance of the arithmetic differences between the scores that are
      assigned to the same stimulus is explained by the stimuli properties. The
      conclusion is that differences between scores that are assigned to the same
      stimulus are not attributable to biases of individual raters; such biases would
      shift all the scores assigned on a scale, and the shift would be interpretable in
      terms of the properties of the stimuli. 

PMID- 24117124
TI  - Acoustic tracking of Cassie to Wenzel wetting transitions.
AB  - Many applications involving superhydrophobic materials require accurate control
      and monitoring of wetting states and wetting transitions. Such monitoring is
      usually done by optical methods, which are neither versatile nor integrable. This
      letter presents an alternative approach based on acoustic measurements. An
      acoustic transducer is integrated on the back side of a superhydrophobic silicon
      surface on which water droplets are deposited. By analyzing the reflection of
      longitudinal acoustic waves at the composite liquid-solid-vapor interface, we
      show that it is possible to track the local evolution of the Cassie-to-Wenzel
      wetting transition efficiently, as induced by evaporation or the electrowetting
      actuation of droplets. 

PMID- 24117125
TI  - Cerebral vasculitis in adults: what are the steps in order to establish the
      diagnosis? Red flags and pitfalls.
AB  - Cerebral vasculitis is a rare cause of juvenile stroke. It may occur as primary
      angiitis of the central nervous system (PACNS) or as CNS manifestation in the
      setting of systemic vasculitis. Clinical hints for vasculitis are headache,
      stroke, seizures, encephalopathy and signs of a systemic inflammatory disorder.
      Diagnostic work-up includes anamnesis, whole body examination, laboratory and
      cerebral spinal fluid (CSF) studies, magnetic resonance imaging (MRI),
      angiography and brain biopsy. Due to the rarity of the disease, exclusion of more
      frequent differential diagnoses is a key element of diagnostic work -up. This
      review summarizes the steps that lead to the diagnosis of cerebral vasculitis and
      describes the red flags and pitfalls. Despite considering the dilemma of
      angiography-negative vasculitis and false-negative brain biopsy in some cases, it
      is important to protect patients from 'blind' immunosuppressive therapy in
      unrecognized non-inflammatory differential diagnosis. 

PMID- 24117126
TI  - Management of Hypertension-Journey from Single Drug Therapy to Multitargeted
      Ligand Therapy: A Clinical Overview.
AB  - Hypertension is recognized as one of the leading risk factors for human morbidity
      and mortality. It is a major risk factor for myocardial infarction, congestive
      heart failure, stroke, and endstage renal disease. The difficulty in controlling
      hypertension is related, at least in part, to the complex pathogenesis of
      hypertension. In spite of the availability of variety of antihypertensive agents,
      the control of blood pressure in the general population is at best inadequate. It
      is being recognized that a balanced modulation of several targets can provide a
      superior therapeutic effect to side effect profile compared to the use of a
      selective ligand. Fixed combinations of drugs and multitargeted ligands provide
      answers to the problem of hypertension. This review provides a status report of
      current antihypertensive drug therapy with fixed combination of drugs and
      evolvement of multitargeted ligands for better management of the disease. 

PMID- 24117127
TI  - DNA protection by the bacterial ferritin Dps via DNA charge transport.
AB  - Dps proteins, bacterial mini-ferritins that protect DNA from oxidative stress,
      are implicated in the survival and virulence of pathogenic bacteria. Here we
      examine the mechanism of E. coli Dps protection of DNA, specifically whether this
      DNA-binding protein can utilize DNA charge transport through the base pair pi
      stack to protect the genome from a distance. An intercalating ruthenium
      photooxidant was employed to generate DNA damage localized to guanine repeats,
      the sites of lowest potential in DNA. We find that Dps loaded with ferrous iron,
      in contrast to Apo-Dps and ferric iron-loaded Dps, significantly attenuates the
      yield of oxidative DNA damage. These data demonstrate that ferrous iron-loaded
      Dps is selectively oxidized to fill guanine radical holes, thereby restoring the
      integrity of the DNA. Luminescence studies indicate no direct interaction between
      the ruthenium photooxidant and Dps, supporting the DNA-mediated oxidation of
      ferrous iron-loaded Dps. Thus DNA charge transport may be a mechanism by which
      Dps efficiently protects the genome of pathogenic bacteria from a distance. 

PMID- 24117129
TI  - The effect of bariatric surgery on echocardiographic indices: a review of the
      literature.
AB  - Obesity is the new epidemic and is associated with an increased risk of diastolic
      and systolic heart failure. Effective treatment options with drastic results such
      as bariatric surgery have raised interest in the possible reversal of some of the
      cardiovascular sequelae. Many studies have assessed individually the effect of
      weight loss on specific echocardiographic indices, mostly employing
      nonhomogeneous groups. The purpose of this narrative review is to summarise the
      effect of bariatric surgery on echocardiographic indices of biventricular
      function and to help in the understanding of the expected echocardiographic
      changes in bariatric patients after weight-loss surgery. 

PMID- 24117128
TI  - Pro-apoptotic TP53 homolog TAp63 is repressed via epigenetic silencing and B-cell
      receptor signalling in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is an accumulative disorder marked by
      deficient apoptosis. The TP53 homolog TAp63 promotes apoptosis and
      chemosensitivity in solid tumours and its deregulation may contribute to CLL cell
      survival. We found that TAp63alpha was the most prevalent TP63 isoform in CLL.
      Compared to healthy B cells, TAp63 mRNA was repressed in 55.7% of CLL samples.
      TP63 promoter methylation was high in CLL and inversely correlated with TP63
      protein expression in B-cell lymphoma cell lines. siRNA-mediated knockdown of
      TP63 resulted in partial protection from spontaneous apoptosis accompanied by
      reductions in PMAIP1 (NOXA), BBC3 (PUMA), and BAX mRNA in CLL cells and increased
      proliferation of Raji lymphoma cells. TAp63 mRNA levels were higher in CLL with
      unmutated IGHV. B-cell receptor (BCR) engagement led to repression of TP63 mRNA
      expression in malignant B cells, while pharmacological inhibition of BCR
      signalling prevented TP63 downregulation. MIR21, known to target TAp63,
      correlated inversely with TAp63 expression in CLL, and BCR-mediated
      downregulation of TP63 was accompanied by MIR21 upregulation in most CLL samples.
      Our data illustrate the pro-apoptotic function of TP63, provide insights into the
      mechanisms of BCR-targeting agents, and establish a rationale for designing novel
      approaches to induce TP63 in CLL and B-cell lymphoma. 

PMID- 24117130
TI  - Antimycobacterial labdane diterpenes from Leucas stelligera.
AB  - Phytochemical investigation of the acetone extract of the aerial parts of Leucas
      stelligera afforded four new compounds (1-4) belonging to the labdane diterpene
      series as well as two known flavones, velutin (5) and chrysoeriol (6). Structure
      elucidation of the new compounds was carried out using 1D and 2D NMR
      spectroscopic data and single-crystal X-ray crystallography of compound 1.
      Compounds 1-4 exhibited selective antimycobacterial activity against
      Mycobacterium tuberculosis with IC50 values in the range 5.02-9.80 MUg/mL. 

PMID- 24117131
TI  - Non-invasive ventilation after surgery in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Surgery in patients affected by amyotrophic lateral sclerosis (ALS)
      presents a particular anesthetic challenge because of the risk of post-operative
      pulmonary complications. AIMS OF THE STUDY: We report on the use of non-invasive
      ventilation (NIV) to prevent post-operative pulmonary complications (PPCs) in
      nine patients affected by ALS enrolled in a phase-1 clinical trial with stem cell
      transplantation. METHODS: All patients were treated with autologous mesenchymal
      stem cells implanted into the spinal cord with a surgical procedure. Anesthesia
      was induced with propofol and maintained with remifentanil and sevoflurane. No
      muscle relaxant was used. After awakening and regain of spontaneous breathing,
      patients were tracheally extubated. Non-invasive ventilation through nasal mask
      was delivered and non-invasive positive pressure ventilation and continuous
      positive pressure ventilation were started. RESULTS: The average time on NIV
      after surgery was 3 h and 12 min. All patients regained stable spontaneous
      breathing after NIV discontinuation and had no episodes of respiratory failure
      until the following day. CONCLUSIONS: Our case series suggest that the use of NIV
      after surgery can be a safe strategy to prevent PPCs in patients affected by ALS.
      The perioperative procedure we chose for these patients appeared safe even in
      patients with advanced functional stage of the disease.

PMID- 24117133
TI  - Tuning the tribological property with thermal sensitive microgels for aqueous
      lubrication.
AB  - Thermoresponsive microgels, poly(N-isopropylacrylamide)-graft-poly(ethylene
      glycol) (PNIPAAm-g-PEG), were synthesized via emulsifier-free emulsion
      polymerization and the tribological property as water lubricating additive was
      studied. The microgels had good thermoresponsive collapse/swelling performance
      with lower critical solution temperature (LCST) ca. 38.4  degrees C. The
      rheological characterization and tribological tests showed that the microgels had
      a good lubricating performance in aqueous lubrication through interfacial
      physisorption and hydration lubrication, but the friction coefficient was
      impacted by temperature (below and above LCST). The tunable thermosensitive
      tribological property was attributed to the hydrophobic interaction and the
      enhanced interfacial absorption, which were both triggered by the elevated
      temperature. Furthermore, in order to avoid the water erosion in aqueous
      lubrication, the microgels were used together with 1H-benzotriazoles (BTA).
      Because of the good antifriction and anticorrosion property of BTA and the
      interplay between microgels and BTA, the microgels/BTA exhibited a synergistic
      effect in aqueous lubrication and the tribological property was more sensitive
      around the LCST. The present work is beneficial to understanding the tribological
      property of responsive microgels in aqueous lubrication and provides a novel
      approach for achieving low-friction through soft matters. 

PMID- 24117134
TI  - Prevalence of intimate partner violence among women seeking termination of
      pregnancy compared to women seeking contraceptive counseling.
AB  - OBJECTIVE: To estimate the prevalence of intimate partner violence (IPV) among
      women seeking termination of pregnancy (TOP) in comparison to women seeking
      contraceptive counseling. DESIGN: Case-control study. SETTING: Family planning
      unit, Uppsala University Hospital. POPULATION: Women seeking TOP (n = 635) and
      women seeking contraceptive counseling (n = 591) answered a self-administered
      questionnaire regarding experience of IPV. In addition, the women were
      interviewed by specially trained staff. METHOD: Comparisons were made between the
      two groups and between those who had previously undergone TOP and those who had
      never done so with experience of IPV as the main outcome measure. Multivariate
      logistic regression was used to adjust for age, education and occupation.
      RESULTS: In total, 29% of women seeking TOP and 22% of women seeking
      contraceptive counseling reported experience of violence. Women seeking TOP were
      more likely to report physical violence [adjusted odds ratio (aOR) = 1.6, 95%
      confidence interval (CI) 1.2-2.1] and experience of violence during the past year
      (aOR = 2.3, 95% Cl 1.1-4.8). Women who had ever undergone TOP were also more
      likely to report IPV compared with women with no history of TOP (aOR = 1.7, 95%
      CI 1.3-2.3). Among women with repeated TOP, 51% reported experience of IPV.
      CONCLUSION: Women seeking TOP reported to a greater extent experience of IPV.
      However, women seeking contraceptive counseling also had a high prevalence of
      violent experiences. These results stress the importance of caregivers
      approaching both groups of women with questions about IPV to identify exposed
      women and offer them help.

PMID- 24117135
TI  - Genetic architecture of isolation between two species of Silene with sex
      chromosomes and Haldane's rule.
AB  - Examination of the genetic architecture of hybrid breakdown can provide insight
      into the genetic mechanisms of commonly observed isolating phenomena such as
      Haldane's rule. We used line-cross analysis to dissect the genetic architecture
      of divergence between two plant species that exhibit Haldane's rule for male
      sterility and rarity, Silene latifolia and Silene diclinis. We made 15 types of
      crosses, including reciprocal F1, F2, backcrosses, and later-generation crosses,
      grew the seeds to flowering, and measured the number of viable ovules, proportion
      of viable pollen, and sex ratio. Typically, Haldane's rule for male rarity in XY
      animal hybrids is explained by interactions involving recessive X-linked alleles
      that are deleterious when hemizygous (dominance theory), whereas sterility is
      explained by rapid evolution of spermatogenesis genes (faster-male evolution). In
      contrast, we found that the genetic mechanisms underlying Haldane's rule between
      the two Silene species did not follow these conventions. Dominance theory was
      sufficient to explain male sterility, but male rarity likely involved faster-male
      evolution. We also found an effect of the neo-sex chromosomes of S. diclinis on
      the extreme rarity of some hybrid males. Our findings suggest that the genetic
      architecture of Haldane's rule in dioecious plants may differ from those commonly
      found in animals.

PMID- 24117136
TI  - Visible photodissociation spectra of the 1- and 2-methylnaphthalene cations:
      laser spectroscopy and theoretical simulations.
AB  - The electronic absorption spectra of the two methyl derivatives of the
      naphthalene cation were measured using an argon tagging technique. In both cases,
      a band system was observed in the visible range and assigned to the D2 <- D0
      electronic transition. The 1-methylnaphthalene(+) absorption bands revealed a red
      shift of 808 cm(-1), relative to those of the naphthalene cation (14,906 cm(-1)),
      whereas for 2-methylnaphthalene(+) a blue shift of 226 cm(-1) appeared. A short
      vibrational progression, similar to the naphthalene cation, was also observed for
      both isomers and found to involve similar aromatic ring skeleton vibrations.
      Moreover, insights into the internal rotation motion of the methyl group were
      inferred, although the spectral resolution was not sufficient to fully resolve
      the substructure. These measurements were supported by detailed quantum chemical
      calculations. They allowed exploration of the potential energy curves along this
      internal coordinate, along with a complete simulation of the harmonic Franck
      Condon factors using the cumulant Gaussian fluctuations formalism extended to
      include the internal rotation.

PMID- 24117137
TI  - Ulcerative sarcoidosis.

PMID- 24117138
TI  - Classification of segmental vitiligo on the trunk.
AB  - BACKGROUND: Segmental vitiligo is characterized by a unilateral and localized
      distribution. A classification for segmental vitiligo on the face has been
      proposed, while this is still unavailable for lesions on the trunk. OBJECTIVES:
      To design a classification for segmental vitiligo lesions on the trunk by
      evaluating their distribution pattern. METHODS: In this retrospective
      observational study, the distribution pattern of 106 segmental vitiligo lesions
      on the trunk was analysed and classified into recurring subtypes. RESULTS:
      Segmental vitiligo was more frequently observed on the ventral side (85.8%) than
      the lateral side (52.8%) or the back (36.8%) of the trunk. Based on recurring
      similarities in distribution patterns, lesions were categorized into six distinct
      subtypes: types 1, 2 and 3 involved the upper part of the trunk, type 4 and 5 the
      middle part and type 6 the lower part of the trunk. In total, 67.9% of all
      segmental vitiligo lesions fitted into these subtypes. The most frequent type of
      lesion was subtype 3 (22.6%), which showed a characteristic V-shaped pattern on
      the upper trunk, followed by subtype 5 (17.9%), with a band-like pattern on the
      lateral side, and subtype 6 (13.2%), with a rectangular depigmentation on the
      lower abdomen. CONCLUSIONS: Based on our observations we suggest a new
      classification into six subtypes for segmental vitiligo lesions on the trunk,
      allowing categorization of the majority of segmental vitiligo patterns on the
      trunk. This may have important prognostic and diagnostic significance in early
      developing lesions.

PMID- 24117139
TI  - Rethinking antioxidants in the intensive care unit.
AB  - Recently there was yet another clinical trial using antioxidants that failed in
      patients with critical illness. In this perspective, we suggest that antioxidants
      likely interfere with the normal immune response, thus contributing to the lack
      of efficacy in patients with critical illness. 

PMID- 24117141
TI  - Bitter taste receptor activation by flavonoids and isoflavonoids: modeled
      structural requirements for activation of hTAS2R14 and hTAS2R39.
AB  - Many flavonoids and isoflavonoids have an undesirable bitter taste, which hampers
      their use as food bioactives. The aim of this study was to investigate the effect
      of a large set of structurally similar (iso)flavonoids on the activation of
      bitter receptors hTAS2R14 and hTAS2R39 and to predict their structural
      requirements to activate these receptors. In total, 68 compounds activated
      hTAS2R14 and 70 compounds activated hTAS2R39, among which 58 ligands were
      overlapping. Their activation threshold values varied over a range of 3 log units
      between 0.12 and 500 MUM. Ligand-based 2D-fingerprint and 3D-pharmacophore models
      were created to detect structure-activity relationships. The 2D models
      demonstrated excellent predictive power in identifying bitter (iso)flavonoids and
      discrimination from inactive ones. The structural characteristics for an
      (iso)flavonoid to activate hTAS2R14 (or hTAS2R39) were determined by 3D
      pharmacophore models to be composed of two (or three) hydrogen bond donor sites,
      one hydrogen bond acceptor site, and two aromatic ring structures, of which one
      had to be hydrophobic. The additional hydrogen bond donor feature for hTAS2R39
      ligands indicated the possible presence of another complementary acceptor site in
      the binding pocket, compared to hTAS2R14. Hydrophobic interaction of the aromatic
      feature with the binding site might be of higher importance in hTAS2R14 than in
      hTAS2R39. Together, this might explain why OH-rich compounds showed different
      behaviors on the two bitter receptors. The combination of in vitro data and
      different in silico methods created a good insight in activation of hTAS2R14 and
      hTAS2R39 by (iso)flavonoids and provided a powerful tool in the prediction of
      their potential bitterness. By understanding the "bitter motif", introduction of
      bitter taste in functional foods enriched in (iso)flavonoid bioactives might be
      avoided. 

PMID- 24117140
TI  - Bitter tasting compounds dilate airways by inhibiting airway smooth muscle
      calcium oscillations and calcium sensitivity.
AB  - BACKGROUND AND PURPOSE: While selective, bitter tasting, TAS2R agonists can relax
      agonist-contracted airway smooth muscle (ASM), their mechanism of action is
      unclear. However, ASM contraction is regulated by Ca2+ signalling and Ca2+
      sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine,
      quinine and denotonium regulate contractile agonist-induced Ca2+ signalling and
      sensitivity. EXPERIMENTAL APPROACH: Airways in mouse lung slices were contracted
      with either methacholine (MCh) or 5HT and bronchodilation assessed using phase
      contrast microscopy. Ca2+ signalling was measured with 2-photon fluorescence
      microscopy of ASM cells loaded with Oregon Green, a Ca2+-sensitive indicator
      (with or without caged-IP3). Effects on Ca2+ sensitivity were assessed on lung
      slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca2+ .
      KEY RESULTS: The TAS2R10 agonists dilated airways constricted by either MCh or
      5HT, accompanied by inhibition of agonist-induced Ca2+ oscillations. However, in
      non-contracted airways, TAS2R10 agonists, at concentrations that maximally
      dilated constricted airways, did not evoke Ca2+ signals in ASM cells. Ca2+
      increases mediated by the photolysis of caged-IP3 were also attenuated by
      chloroquine, quinine and denotonium. In Ca2+-permeabilized ASM cells, the TAS2R10
      agonists dilated MCh- and 5HT-constricted airways. CONCLUSIONS AND IMPLICATIONS:
      TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca2+
      oscillations while simultaneously reducing the Ca2+ sensitivity of ASM cells.
      Reduction of Ca2+ oscillations may be due to inhibition of Ca2+ release through
      IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may
      lead to the development of novel therapies for the treatment of
      bronchoconstrictive conditions.

PMID- 24117142
TI  - Efficient enzymatic synthesis of guanosine 5'-diphosphate-sugars and derivatives.
AB  - An N-acetylhexosamine 1-kinase from Bifidobacterium infantis (NahK_15697), a
      guanosine 5'-diphosphate (GDP)-mannose pyrophosphorylase from Pyrococcus furiosus
      (PFManC), and an Escherichia coli inorganic pyrophosphatase (EcPpA) were used
      efficiently for a one-pot three-enzyme synthesis of GDP-mannose, GDP-glucose,
      their derivatives, and GDP-talose. This study represents the first facile and
      efficient enzymatic synthesis of GDP-sugars and derivatives starting from
      monosaccharides and derivatives. 

PMID- 24117143
TI  - Cell-derived polymer/extracellular matrix composite scaffolds for cartilage
      regeneration, Part 2: construct devitalization and determination of
      chondroinductive capacity.
AB  - This work examined the chondrogenic potential of chondrocyte and mesenchymal stem
      cell (MSC) coculture generated poly(E-caprolactone) (PCL)/extracellular matrix
      (ECM) hybrid scaffolds. Five different ratios of chondrocytes and MSCs were
      cocultured to generate cartilage-like ECM within electrospun fibrous scaffolds
      for 7, 14, and 21 days. These constructs were then devitalized to isolate the
      chondrogenic effects of the ECM alone. Devitalization was successful at removing
      cellular matter from the scaffolds, yet did reduce the amount of matrix present
      in the scaffolds. Following devitalization, the PCL/ECM scaffolds were then
      cultured with MSCs in serum-free conditions with or without TGF-beta3 treatment
      for 21 days. TGF-beta3 supplemented culture caused an induction of chondrogenesis
      in each scaffold type, but also somewhat masked the subtle differences of the
      different ECM coatings. Without TGF-beta3, the cartilaginous matrix generated by
      1:1 cocultures of chondrocytes to MSCs for 14 days supported similar chondrogenic
      gene expression patterns of MSCs cultured on scaffolds generated by chondrocytes
      alone. These scaffold formulations had a positive chondrogenic effect on
      aggrecan, collagen type II, and collagen II/I expression when compared to PCL
      controls. This study demonstrates that it is possible to utilize cocultures of
      chondrocytes and MSCs to coat a polymer scaffold with cartilage-like ECM capable
      of supporting chondrogenic differentiation of MSCs. 

PMID- 24117144
TI  - Multiple self-controlled case series for large-scale longitudinal observational
      databases.
AB  - Characterization of relationships between time-varying drug exposures and adverse
      events (AEs) related to health outcomes represents the primary objective in
      postmarketing drug safety surveillance. Such surveillance increasingly utilizes
      large-scale longitudinal observational databases (LODs), containing time-stamped
      patient-level medical information including periods of drug exposure and dates of
      diagnoses for millions of patients. Statistical methods for LODs must confront
      computational challenges related to the scale of the data, and must also address
      confounding and other biases that can undermine efforts to estimate effect sizes.
      Methods that compare on-drug with off-drug periods within patient offer specific
      advantages over between patient analysis on both counts. To accomplish these
      aims, we extend the self-controlled case series (SCCS) for LODs. SCCS implicitly
      controls for fixed multiplicative baseline covariates since each individual acts
      as their own control. In addition, only exposed cases are required for the
      analysis, which is computationally advantageous. The standard SCCS approach is
      usually used to assess single drugs and therefore estimates marginal associations
      between individual drugs and particular AEs. Such analyses ignore confounding
      drugs and interactions and have the potential to give misleading results. In
      order to avoid these difficulties, we propose a regularized multiple SCCS
      approach that incorporates potentially thousands or more of time-varying
      confounders such as other drugs. The approach successfully handles the high
      dimensionality and can provide a sparse solution via an L1 regularizer. We
      present details of the model and the associated optimization procedure, as well
      as results of empirical investigations.

PMID- 24117145
TI  - A protective role of sulforaphane on alveolar epithelial cells exposed to
      cigarette smoke extract.
AB  - BACKGROUND: Sulforaphane (SFN) is an excellent antioxidant agent, few of the
      studies focus on the possible protective role of SFN from cigarette smoke-induced
      injury on alveolar epithelial cells. OBJECTIVES: the aim of the study is to
      observe the possible protective role of SFN, as well as the function of insulin
      like growth factor binding protein-3 (IGFBP-3) in the process. METHODS: MTT assay
      was used to evaluate cell viability after cigarette smoke extract (CSE) and/or
      SFN exposure, cell cycle was analyzed using flow cytometry, intracellular
      reactive oxygen species (ROS) level was detected by staining with fluorescent
      indicator 2', 7'-dichlorofluorescin diacetate (DCFH-DA), finally both real-time
      quantitative RT-PCR and western blot were employed to observe mRNA and protein
      levels of IGFBP-3. RESULTS: SFN could restore the viability of A549 cells,
      attenuate G1 block of the cell cycle, and significantly reduce the proportion of
      sub-G1 cells; at the same time, CSE-induced accumulation of intracellular ROS was
      decreased by SFN. Interestingly, high expression of IGFBP-3 was found at both
      transcriptional and translational levels, however by pre-incubation with SFN, the
      expression of IGFBP-3 was not stimulated by CSE exposure. CONCLUSIONS: SFN can
      antagonize CSE-induced growth arrest of alveolar epithelial cells and IGFBP-3
      probably plays an important role in the process.

PMID- 24117146
TI  - Novel homozygous mutation in exon 5 of WFS1 gene in an Apulian family with mild
      phenotypic expression of Wolfram syndrome.

PMID- 24117147
TI  - The relationship between lifestyle and self-reported oral health among American
      adults.
AB  - OBJECTIVES: Whereas an unhealthy lifestyle is a risk factor for chronic disease,
      its relationship to self-reported oral health is unclear. This paper studies this
      relationship among American adults using two dimensions of self-reported oral
      health, namely: (1) the extent to which a person's teeth are in poor condition,
      simply called 'bad teeth'; (2) the occurrences of negative consequences of poor
      oral health, simply called 'bad experience'. The main purpose of this study is to
      describe and assess their relationship to four markers of lifestyles and to use
      the results to make recommendations on improving oral health. METHODS: Data were
      obtained from National Health and Nutrition Examination Survey (NHANES) 2005
      2006. A series of logistic regression models quantified the associations between
      lifestyle markers with self-reported oral health. RESULTS: Our major findings are
      that: (1) individuals who smoked every day were significantly more likely to have
      bad teeth and a bad oral experience than non-smokers, with risk ratios of 1.61
      (95% CI 1.36, 1.92) and 1.50 (95% CI 1.24, 1.8), respectively; (2) individuals
      who had poor diets were more likely to report bad teeth and have bad oral
      experiences than those who had excellent diets, with risk ratios of 4.22 (95% CI
      2.8, 6.28) and 2.88 (95% CI 1.83, 4.55), respectively, both comparisons adjusted
      for other demographic variables. CONCLUSIONS: These results suggest that self
      reported indicators of oral health could be used to guide people in making
      improvements in their life style that could result in better oral health,
      especially for disadvantaged individuals.

PMID- 24117149
TI  - Expression and purification of recombinant human bone morphogenetic protein-7 in
      Escherichia coli.
AB  - Bone morphogenetic protein-7 (BMP-7) is a multifunctional cytokine of the
      transforming growth factor beta superfamily, which induces bone formation and
      plays an important role during bone tissue repair and embryonic development. In
      this study, human BMP-7 (hBMP-7) cDNA was cloned and expressed in Escherichia
      coli, and its yield was approximately 30% of the total bacterial protein. After
      the bacteria were lysed by ultrasonication and repeated washing, inclusion bodies
      were extracted and dissolved using a high-strength denaturant. The monomer of
      rhBMP-7 was purified by ion-exchange chromatography, and the purity coefficient
      was approximately 96%. The protein was renatured with refolding buffers at
      different pH values. The renatured rhBMP-7 dimer protein in this study increased
      the alkaline phosphatase activity of NIH3T3 cells. This study may be helpful for
      the in vitro production and biomedical application of rhBMP-7 protein expressed
      in an E. coli expression system. 

PMID- 24117148
TI  - Extraction, purification, and characterization of a trypsin inhibitor from cowpea
      seeds (Vigna unguiculata).
AB  - Protease inhibitors against trypsin were extracted from cowpea seeds, purified,
      and characterized. After the seed powder was defatted with hexane, the cowpea
      trypsin inhibitor (CpTI) was extracted with 0.15 M NaCl for 30 min. The crude
      extracts were then heated at 90 degrees C for 10 min, followed by precipitation
      with 40-65% saturation ammonium sulfate, by which the protein purity increased
      approximately 15-fold. The CpTI had approximate 88-fold and 186-fold purification
      after anion-exchange chromatography (Super-Q) and gel filtration (Sephadex G
      200), respectively. A broad band of the purified CpTI on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) indicates a degree of heterogeneity
      and partial denaturation of CpTI, having a molecular mass of ~8000 kD. Multiple
      peaks between 7451 and 8898 by matrix-assisted laser desorption/ionization time
      of-flight (MALDI-TOF) mass spectroscopy also suggest heterogeneity. The purified
      CpTI was stable at 90 degrees C for 60 min, pH 5-10, and 0-3.0% of NaCl. The
      purification method described here can be used to obtain highly purified CpTI for
      its studies such as risk assessment of CpTI genetically modified foods. 

PMID- 24117150
TI  - Exploring the optimum conditions for maximizing the microbial growth of Candida
      intermedia by response surface methodology.
AB  - Exploring optimum and cost-efficient medium composition for microbial growth of
      Candida intermedia Y-1981 yeast culture growing on whey was studied by applying a
      multistep response surface methodology. In the first step, Plackett-Burman (PB)
      design was utilized to determine the most significant fermentation medium factors
      on microbial growth. The medium temperature, sodium chloride and lactose
      concentrations were determined as the most important factors. Subsequently, the
      optimum combinations of the selected factors were explored by steepest ascent
      (SA) and central composite design (CCD). The optimum values for lactose and
      sodium chloride concentrations and medium temperature were found to be 18.4 g/L,
      0.161 g/L, and 32.4 degrees C, respectively. Experiments carried out at the
      optimum conditions revealed a maximum specific growth rate of 0.090 1/hr; 42% of
      total lactose removal was achieved in 24 h of fermentation time. The obtained
      results were finally verified with batch reactor experiments carried out under
      the optimum conditions evaluated. 

PMID- 24117151
TI  - The optimization of saccharification of desulfurated red seaweed-derived
      polysaccharides and analysis of their composition.
AB  - Currently processes of ethanol production from desulfurated red seaweed derived
      polysaccharides (De-RSDP) are well established. However, the optimization of the
      enzymatic saccharification process has not been reported. In this study, De-RSDP
      from Kappaphycus alvarezii was subjected to saccharification by different
      enzymes, including pectinase, cellobiase, cellulase, and hemicellulase. The best
      saccharification enzyme was determined as pectinase. In order to obtain more
      reducing sugar (RS), the single-factor experiment followed by central composite
      rotatable design (CCD) was used to optimize the parameters for enzymatic
      hydrolysis. The optimal saccharification parameters of De-RSDP were 4400 U/g
      pectinase dosage, 96 hr, and 55.5 degrees C, respectively, and the yield of RS
      reached 81.3%. Subsequently, the saccharification liquids of De-RSDP were
      isolated and purified with gel permeation chromatography (GPC) to separate
      saccharides with different molecular weights. Simultaneously, the composition of
      saccharification liquids was analyzed by 1-phenyl-3-methyl-5-pyrazolone high
      pressure liquid chromatography (PMP-HPLC) and mass spectroscopy (MS). The result
      showed that the content is mainly composed of galactose (65.2%) with the average
      molecular mass in the fourth peak 181.1 Da. The saccharification liquids of De
      RSDP inoculated with Saccharomyces cerevisiae L-4 for ethanol fermentation
      produced 0.3 g ethanol/g De-RSDP, which corresponded to 71.8% of the theoretical
      yield (0.38 g ethanol/g). 

PMID- 24117152
TI  - Model development and process optimization for solvent extraction of polyphenols
      from red grapes using Box-Behnken design.
AB  - The objective of the present study is to find out the optimum extraction
      conditions for extraction of polyphenols from red grapes using Box-Behnken
      design. Red grapes polyphenols were extracted using acid-ethanol solvent at
      various extraction temperature (40-60 degrees C), extraction time (20-100 min)
      and different solid-liquid ratio (1:5-1:15 g:ml). The effect (main and
      interactive) of extraction conditions on total anthocyanin, phenolic and
      flavonoid content were studied using Box-Behnken design (three factors at three
      levels). The results showed that the contribution of the quadratic model was
      significant for all the responses. Second-order mathematical regression models
      were developed and were found to fit well with observed data. Derringer's
      desirability function methodology was performed to find out the optimal
      conditions based on both individual and combinations of all responses (extraction
      temperature: 57 degrees C, time: 61 min, and solid-liquid ratio: 1:8.7 g:ml) were
      established. At this optimal condition, the anthocyanin yield, total phenolic and
      flavonoid content were 73.92 mg/100 g, 221.4 mg GAE/100 g, and 79.08 mg CE/100 g,
      respectively. A desirability value of 0.902 was achieved at this point. 

PMID- 24117153
TI  - Statistical optimization of pigment production by Monascus sanguineus under
      stress condition.
AB  - Natural pigments are produced by the Monascus sp., which are used for coloring
      food substances. The intent of this study was to optimize the pigment yield and
      biomass produced from the unexplored Monascus sanguineus in submerged culture
      under stress conditions. For inducing thermal stress, the spores were incubated
      at various temperatures at higher ranges. For inducing osmotic stress, varied
      concentrations of NaCl, glycerol, and peptone were used. The medium components
      were optimized by response surface methodology (RSM). The combined effects of the
      four medium constituents mentioned were studied using a 24 full factorial central
      composite design (CCD). The relationships between the predicted values and actual
      values, independent variable, and the response were calculated according to a
      second-order quadratic model. It was deduced that the variable with the leading
      effect was the linear effect of glycerol concentration. Furthermore, the
      quadratic effects of peptone and the interactive effects of temperature and
      glycerol were more noteworthy than other factors. The optimum values for the test
      variables in coded factors were found to be spores treated with 70 degrees C for
      temperature, 0.25 M for glycerol, 0.51% (w/v) for peptone, and 1.25% (w/v) for
      NaCl, corresponding to a maximum red pigment yield of 55.67 color value units
      (CVU)/mL. With optimized conditions, the pigment yield was almost three times the
      yield observed with the control.

PMID- 24117154
TI  - Extractive fermentation of gibberellic acid with free and immobilized Gibberella
      fujikuroi.
AB  - Gibberelic acid fermentation using extractive methods was carried out in the
      presence of corn oil and Alamine 336. Gibberella fujikuroi fungus (NRRL 2278) was
      used to produce gibberellic acid. Oleyl alcohol was a diluting agent for Alamine
      336. The effects of oleyl alcohol (100%, v/v), corn oil (5-25%, v/v), the
      concentration of Alamine 336 in oleyl alcohol, and feeding air were examined in
      this study. According to the results, oleyl alcohol was not effective on the
      production. On the other hand, oleyl alcohol solutions containing 15-30% (v/v)
      Alamine 336 showed effects as a toxic substance. In order to reduce solvent
      toxicity, corn oil was used. Addition of corn oil increased the concentration of
      gibberellic acid 1.3-fold compared to the control. Then the effects of
      immobilization and co-immobilization on extractive gibberelic acid fermentation
      were investigated. The highest total gibberellic acid concentration of 158.9 mg/L
      was produced with immobilized cells and feeding air by using extractive
      fermentation. The yield of gibberellic acid increased about 2.6-fold compared
      with the shake-flask fermentation (60.5 mg/L) without organic solutions. 

PMID- 24117155
TI  - Optimization of fermentation conditions and purification of cordycepin from
      Cordyceps militaris.
AB  - The fermentation medium and conditions for the production of cordycepin were
      optimized in static culture using single-factor experiments, Placket-Burman
      design, a central composite design, and response surface methodology. Among seven
      variables including temperature, pH, and the concentrations of glucose, tryptone,
      yeast extract, KH2PO4, and MgSO4 . 7H2O, temperature and the concentrations of
      yeast extract and tryptone were found to be the important factors that
      significantly affected cordycepin production. The optimized medium consisted of
      yeast extract 9.00 g/L and tryptone 17.10 g/L, while the optimized culture
      conditions consisted of seed age 3 days, with an inoculum size of 10% and
      incubation temperature of 27.1 degrees C. A maximum cordycepin yield of 7.35 g/L
      was achieved in a 5-L fermenter under the optimized conditions. Next, cordycepin
      was partially purified and determined. The resulting product showed 90.54% high
      performance liquid chromatography (HPLC)-ultraviolet (UV) purity. Therefore,
      cordycepin was applied to a cell viability assay on SH-SY5Y cells and RM-1 cells.
      Cordycepin can inhibit the proliferation of RM-1 cells with IC50 of 133 umol/L,
      but it has no inhibitory effect on SH-SY5Y cells. Supplemental materials are
      available for this article.

PMID- 24117157
TI  - Synthesis of nanobioconjugates with a controlled average number of biomolecules
      between 1 and 100 per nanoparticle and observation of multivalency dependent
      interaction with proteins and cells.
AB  - Multivalency of nanoparticle and associated cooperative binding with biological
      interface is an important aspect in the development of nanoparticle based
      bioimaging probes. However, the preparation of such a nanobioconjugate with a
      controlled number of biomolecules per nanoparticle, typically between 1 and 100,
      is challenging. Here we report a generalized two-step bioconjugation method to
      prepare nanobioconjugates with a varied average number of biomolecules between 1
      to 100 per nanoparticle that can be applied to different nanoparticles and
      biomolecules. Following this approach we have successfully synthesized quantum
      dot (QD) based bioconjugates with controlled average numbers of glucose or folate
      and found their number-dependent interaction with proteins and cells. We propose
      a method for exploiting the nanoparticle multivalency effect toward various
      biological interactions and preparing such nanobioconjugates for best
      performance. 

PMID- 24117158
TI  - Isolation of the large {actinide}38 poly-oxo cluster with uranium.
AB  - By controlling the water content, a new poly-oxo-metalate species containing 38
      uranium centers has been solvothermally synthesized in the presence of benzoic
      acid in tetrahydrofuran (THF). The {U38} motif contains a distorted UO2 core of
      fluorite type, stabilized by benzoate and THF molecules. This compound is
      analogous to the {Pu38} motif and was characterized by X-ray photoelectron
      spectroscopy and magnetic analyses. 

PMID- 24117156
TI  - JNK signalling in cancer: in need of new, smarter therapeutic targets.
AB  - The JNKs are master protein kinases that regulate many physiological processes,
      including inflammatory responses, morphogenesis, cell proliferation,
      differentiation, survival and death. It is increasingly apparent that persistent
      activation of JNKs is involved in cancer development and progression. Therefore,
      JNKs represent attractive targets for therapeutic intervention with small
      molecule kinase inhibitors. However, evidence supportive of a tumour suppressor
      role for the JNK proteins has also been documented. Recent studies showed that
      the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing
      functions in different types of cancer. As such, close consideration of which JNK
      proteins are beneficial targets and, more importantly, what effect small molecule
      inhibitors of JNKs have on physiological processes, are essential. A number of
      ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but
      have several limitations such as a lack of specificity and cellular toxicity. In
      this review, we summarize the accumulating evidence supporting a role for the JNK
      proteins in the pathogenesis of different solid and haematological malignancies,
      and discuss many challenges and scientific opportunities in the targeting of JNKs
      in cancer. 

PMID- 24117159
TI  - Guideline on the management of primary resistant and relapsed classical Hodgkin
      lymphoma.

PMID- 24117160
TI  - Increased platelet oxidative metabolism, blood oxidative stress and neopterin
      levels after ultra-endurance exercise.
AB  - The purpose of the present investigation was to identify muscle damage,
      inflammatory response and oxidative stress blood markers in athletes undertaking
      the ultra-endurance MultiSport Brazil race. Eleven well-trained male athletes
      (34.3 +/- 3.1 years, 74.0 +/- 7.6 kg; 172.2 +/- 5.1 cm) participated in the study
      and performed the race, which consisted of about 90 km of alternating off-road
      running, mountain biking and kayaking. Twelve hours before and up to 15 minutes
      after the race a 10 mL blood sample was drawn in order to measure the following
      parameters: lactate dehydrogenase and creatine kinase activities, lipid
      peroxidation, catalase activity, protein carbonylation, respiratory chain
      complexes I, II and IV activities, oxygen consumption and neopterin
      concentrations. After the race, plasma lactate dehydrogenase and creatine kinase
      activities were significantly increased. Erythrocyte TBA-RS levels and plasma
      protein carbonylation were markedly augmented in post-race samples. Additionally,
      mitochondrial complex II activity and oxygen consumption in post-race platelet
      rich plasma were also increased. These altered biochemical parameters were
      accompanied by increased plasma neopterin levels. The ultra-endurance event
      provoked systemic inflammation (increased neopterin) accompanied by marked
      oxidative stress, likely by increasing oxidative metabolism (increased oxidative
      mitochondrial function). This might be advantageous during prolonged exercise,
      mainly for efficient substrate oxidation at the mitochondrial level, even when
      tissue damage is induced.

PMID- 24117161
TI  - Multiple superficial and pigmented basal cell carcinomas: do these represent a
      type of multiple non-syndromic basal cell carcinoma?

PMID- 24117162
TI  - Impact of hypertension and renin-angiotensin system inhibitors in aortic
      stenosis.
AB  - BACKGROUND: Experimental studies revealed that renin-angiotensin system (RAS)
      could play a crucial role in the pathophysiology of aortic stenosis (AS). The
      objectives of this study were to examine (i) the impact of hypertension on AS
      progression and clinical events and (ii) the effect of angiotensin-converting
      enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs). MATERIALS AND
      METHODS: In this observational study, we retrospectively analysed clinical and
      Doppler echocardiographic data prospectively collected in 338 patients with AS.
      Patients were separated into four groups: patients without hypertension and not
      treated by RAS medication (Ctrl group), patients with hypertension but not
      treated by RAS medication (HTN group), patients treated with ACEIs, and patients
      treated with ARBs. AS progression rate was assessed by the annualized increase in
      peak aortic jet velocity. RESULTS: Compared with Ctrl group, patients in HTN
      group had faster stenosis progression (P = 0.01). Patients on ARBs had slower AS
      progression compared with Ctrl (trend P = 0.10) and HTN (P = 0.002) groups,
      whereas patients on ACEIs had similar progression rate compared with Ctrl group
      (P = NS) but lower compared with HTN group (P = 0.02). On multivariable analysis,
      compared with Ctrl group, HTN group was associated with faster AS progression
      rate (P = 0.002), whereas ARBs with slower progression (P = 0.0008). During a
      mean follow-up of 6.2 +/- 2.4 years, HTN (hazard ratio [HR] = 2.45; P = 0.006)
      and ACEI (HR = 2.30; P = 0.01) groups were associated with a significant increase
      in all-cause mortality compared with Ctrl group, whereas ARB group (HR: 0.89; P =
      0.80) not. In multivariable analysis, HTN and ACEI groups remained associated
      with increased mortality. CONCLUSIONS: Hypertension is associated with
      significantly faster stenosis progression and higher incidence of clinical events
      in patients with AS. ARBs but not ACEs were found to abolish the increased risk
      of mortality associated with hypertension.

PMID- 24117163
TI  - CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in
      hereditary spastic paraplegia type 5A.
AB  - The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal
      recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene,
      which encodes a steroid cytochrome P450 7alpha-hydroxylase. This enzyme provides
      the primary metabolic route for neurosteroids. Clinically, SPG5A has been
      characterized as a pure form of HSP with a variable age of onset, but recently a
      broader spectrum of phenotypes has been described. OBJECTIVE: This study
      characterizes four unrelated SPG5A patients through clinical evaluation. METHODS:
      The investigations included blood biochemistry, electrophysiology, brain MRI and
      MR spectroscopy. RESULTS: One patient had saccadic pursuit eye movements in
      addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations
      revealed prolonged central conduction time. MRI of the brain showed white matter
      hyperintensities (WMH) in one patient. MRS showed elevated mI/Cr ratio in white
      matter in two patients; in the one patient with WMH and in one patient with
      normal MRI. Four novel mutations were identified; one frameshift (c.509 delT
      p.L170fs), one premature stop codon (c.334 C>T p.R112X), one amino acid changing
      (c.440 G>A p.G147D) and one duplication (c.945_947 dupGGC p.A316AA). CONCLUSION:
      SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated
      mI/Cr ratio in the white matter may be indicative of SPG5A.

PMID- 24117164
TI  - Redox pioneer: Professor Joe M. McCord.
AB  - Dr. Joe McCord (Ph.D. 1970) is recognized here as a Redox Pioneer because he has
      published at least three articles on antioxidant/redox biology as first/last
      author that have been cited over 1000 times and has published at least 37
      articles each cited over 100 times. Dr. McCord is known for the monumental
      discovery of the antioxidant superoxide dismutase (SOD) while a graduate student
      under fellow redox pioneer Irwin Fridovich and demonstrating its necessity to
      aerobic life. Beyond this, McCord's career is distinguished for bridging the gap
      from basic science to clinical relevance by showing the application of SOD and
      superoxide to human physiology, and characterizing the physiological functions of
      superoxide in inflammation, immunological chemotaxis, and ischemia-reperfusion
      injury, among other disease conditions. Work by McCord serves as the foundation
      upon which our understanding of how superoxide functions in a variety of
      physiological systems is built and demonstrates how superoxide is essential to
      aerobic life, yet, if left unchecked by SOD, toxic to a multitude of systems.
      These discoveries have substantial significance in a wide range of studies with
      applications in cardiovascular disease, cancer, neurology, and medicine, as well
      as general health and longevity. Dr. McCord's contributions to free radical
      biology have been recognized through many prestigious achievement awards,
      honorary titles, and conferences around the world; each serving as a testament to
      his status as a redox pioneer.

PMID- 24117166
TI  - Antidrug antibodies in psoriasis: a systematic review.
AB  - Antidrug antibodies (ADAs) against biological agents may be clinically
      significant and potentially alter a biological drug's treatment efficacy. This
      systematic review aims to (i) determine the prevalence of ADAs against
      infliximab, etanercept, adalimumab and ustekinumab in patients with psoriasis;
      (ii) ascertain whether ADAs are associated with changes in drug efficacy; and
      (iii) explore the use of concomitant methotrexate to prevent ADA formation.
      Through a systematic search using Medline and Embase from 29 January 1950 to 29
      March 2013, we identified 25 studies that met the inclusion criteria. Of 7969
      patients with psoriasis, 950 tested positive for ADAs. Antibodies against
      infliximab, etanercept, adalimumab and ustekinumab were reported in 5.4-43.6%, 0
      18.3%, 6-45% and 3.8-6% of patients, respectively. Anti-infliximab antibodies
      were associated with lower serum infliximab concentrations in three studies, and
      decreased treatment response in five studies. ADAs against etanercept were non
      neutralizing and not associated with any apparent effects on clinical response.
      Antiadalimumab antibodies were associated with lower serum adalimumab
      concentrations in three of five studies, and reduced clinical efficacy in four
      studies. Two of six studies reported that antiustekinumab antibodies were
      associated with lower Psoriasis Area and Severity Index responses, and three
      ustekinumab studies noted that most of these antibodies were neutralizing.
      Although the use of concomitant methotrexate with biological agents to prevent
      ADA formation in other immune-mediated diseases is promising, their use in
      psoriasis is sparse. ADA development remains a challenge with biological
      therapies and therefore should be considered in patients with psoriasis who
      experience diminished treatment response. 

PMID- 24117167
TI  - Effect of measurement duration on accuracy of pulse-counting.
AB  - In this study, the relation between the measurement duration and accuracy of
      pulse-counting was quantitatively examined with special reference to low
      frequency fluctuations in heart rate variability. The interbeat intervals of 70
      healthy male subjects were measured in standing, sitting and supine positions.
      Pulse rates for various durations were calculated by objective-scoring simulation
      based on the heartbeat recordings of the subjects. The duration of pulse-counting
      continuously varied from 6 to 60 s in the simulation. Simulated pulse rates were
      compared with the rate calculated from the 60 s that includes the given duration,
      and the absolute difference between the two rates was defined as the error.
      Average errors of pulse-counting for 15 s were 1.89, 1.89 and 1.80 bpm for
      standing, sitting and supine positions, respectively. No difference in error was
      observed between standing and sitting positions; however, smaller errors were
      observed in the supine position. 

PMID- 24117168
TI  - Photocatalyzed conversion of CO2 to CH4: an excited-state acid-base mechanism.
AB  - Photoinduced reduction of CO2 by H2O occurs in nanoporous Vycor glass doped with
      tungsten oxides derived from 312 nm photolysis of physisorbed W(CO)6. In polished
      forms of Vycor, a hydrated precursor to monoclinic WO3 is formed, whereas in the
      unpolished glass, the WO3 precursor and mixed valence tungsten oxides that
      exhibit lower energy intervalence charge transfer (IVCT) transitions are formed.
      The relative amounts of the different tungsten oxide are attributed to structural
      differences between the polished and unpolished forms of PVG. Chemisorption
      converts CO2 to a formic acid-like species, and population of the conduction band
      of the WO3 precursor with 312 nm light or population of the IVCT state of the
      mixed valence oxide with >=437 nm light photocatalyzes the reduction of
      chemisorbed by coadsorbed water yielding CH4 and O2. Regardless of the excitation
      wavelength, electronic spectra and the dependence of methane yield on absorbed
      energy and the energetics of the conversions implies that neither metal oxide
      acts as a source of reducing equivalents. Instead, excitation of the metal oxide
      induces a charge polarization that creates local acidic and basic regions about
      the oxide in which the reduction of chemisorbed CO2 and oxidation of chemisorbed
      H2O occur exergonically. The dependence of methane yield on surface pH, and the
      pH dependencies of the respective half reactions show that the pH gradient needed
      for the reactions to occur spontaneously fall within the range of known
      photoinduced changes in acid-base properties. Within this excited-state acid-base
      mechanism, the metal oxide is not a source of electrons, but a conduit of
      electrons and protons between two exergonic processes. 

PMID- 24117169
TI  - Experimental evolution of female traits under different levels of intersexual
      conflict in Drosophila melanogaster.
AB  - A number of studies have documented the evolution of female resistance to mate
      harm in response to the alteration of intersexual conflict in the populations.
      However, the life-history consequence of such evolution is still a subject of
      debate. In this study, we subjected replicate populations of Drosophila
      melanogaster to different levels of sexual conflict (generated by altering the
      operational sex ratio) for over 45 generations. Our results suggest that females
      from populations experiencing higher level of intersexual conflict evolved
      increased resistance to mate-harm, in terms of both longevity and progeny
      production. Females from the populations with low conflict were significantly
      heavier at eclosion and were more susceptible to mate-harm in terms of progeny
      production under continuous exposure to the males. However, these females
      produced more progeny upon single mating and had significantly higher longevity
      in absence of any male exposure-a potential evidence of trade-offs between
      resistance-related traits and other life-history traits, such as fecundity and
      longevity. We also report tentative evidence, suggesting an increased male cost
      of interacting with more resistant females. 

PMID- 24117165
TI  - First-in-class cardiolipin-protective compound as a therapeutic agent to restore
      mitochondrial bioenergetics.
AB  - A decline in energy is common in aging, and the restoration of mitochondrial
      bioenergetics may offer a common approach for the treatment of numerous age
      associated diseases. Cardiolipin is a unique phospholipid that is exclusively
      expressed on the inner mitochondrial membrane where it plays an important
      structural role in cristae formation and the organization of the respiratory
      complexes into supercomplexes for optimal oxidative phosphorylation. The
      interaction between cardiolipin and cytochrome c determines whether cytochrome c
      acts as an electron carrier or peroxidase. Cardiolipin peroxidation and depletion
      have been reported in a variety of pathological conditions associated with energy
      deficiency, and cardiolipin has been identified as a target for drug development.
      This review focuses on the discovery and development of the first cardiolipin
      protective compound as a therapeutic agent. SS-31 is a member of the Szeto
      Schiller (SS) peptides known to selectively target the inner mitochondrial
      membrane. SS-31 binds selectively to cardiolipin via electrostatic and
      hydrophobic interactions. By interacting with cardiolipin, SS-31 prevents
      cardiolipin from converting cytochrome c into a peroxidase while protecting its
      electron carrying function. As a result, SS-31 protects the structure of
      mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a
      new class of compounds that can recharge the cellular powerhouse and restore
      bioenergetics. Extensive animal studies have shown that targeting such a
      fundamental mechanism can benefit highly complex diseases that share a common
      pathogenesis of bioenergetics failure. This review summarizes the mechanisms of
      action and therapeutic potential of SS-31 and provides an update of its clinical
      development programme.

PMID- 24117170
TI  - Differential expression and activation of epidermal growth factor receptor 1
      (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC).
AB  - Lung cancer is the leading cause of death of both men and women across the world.
      Overexpression and activating mutations of the epidermal growth factor receptor-1
      (EGFR1) are frequently observed and associated with poor prognosis. To inhibit
      the function of EGFR1, multiple antibodies and small-molecule tyrosine kinase
      inhibitors (TKI) that target EGFR1 have been developed. Even though some patients
      respond to these TKI, subsequent studies reveal that this is not the case for all
      nonsmall cell lung cancer (NSCLC) patients. In this study, we determine whether
      activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are
      dependent on the activating mutations of EGFR1. Protein lysates and DNA have been
      isolated from tumor and corresponding normal tissues of 16 NSCLC patients.
      Genomic-DNA is used to sequence the exons 18, 19, and 21 of EGFR1, and exon 2 of
      k-RAS. Protein lysates were used to determine the expression or phosphorylation
      levels of EGFR, STAT3, ERK, AKT, and TWIST1. Our results revealed that 16 tumor
      samples of NSCLC patients showed no mutation in any of the indicated exons of
      EGFR1 and k-RAS albeit significant levels of activation or expression of the
      above-mentined oncogenes. In NSCLC patients, the tumor micro-environment can be
      as important as the activating mutations of EGFR1. TK therapy may also be
      considered for patients who show high levels of activation of EGFR1 even in the
      absence of activating mutations.

PMID- 24117171
TI  - An unusual Michael-induced skeletal rearrangement of a bicyclo[3.3.1]nonane
      framework of phloroglucinols to a novel bioactive bicyclo[3.3.0]octane.
AB  - A novel skeletal rearrangement of bicyclo[3.3.1]nonane-2,4,9-trione (16) to an
      unprecedented highly functionalized bicyclo[3.3.0]octane system (17), induced by
      an intramolecular Michael addition, is presented. This novel framework was found
      to be similarly active to hyperforin (1), against PC-3 cell lines. A mechanistic
      study was examined in detail, proposing a number of cascade transformations.
      Also, reactivity of the Delta(7,10)-double bond was examined under several
      conditions to explain the above results. 

PMID- 24117172
TI  - Social disparities in dentition status among American adults.
AB  - OBJECTIVES: To assess the overall dentition status of American adults, to
      investigate disparities and changes in dentition using the National Health and
      Nutrition Examination Surveys 2005-2006 and 2007-2008 and to study the effects of
      family poverty status, education, citizenship and language on dentition after
      adjusting for other demographics. METHODS: Descriptive statistics were used to
      explore and summarise dentition status. The prevalence of dentition markers over
      two surveys were compared using tests of proportions and a series of regressions
      were used to estimate the strength of association of family poverty status,
      education, citizenship and language with the four markers of dentition status.
      RESULTS: Overall, dentition status has improved in adults. However, gaps exist in
      that non-Hispanic Black and Mexican-Americans have a higher prevalence of dental
      decay and lower restoration rates than other races. After adjusting for selected
      demographics, adults with less education (<12 years) and lower family income had
      significantly higher dental decay rates, lower restoration rates and more missing
      teeth than those with more education (>=12 years) and those with higher family
      incomes. CONCLUSION: This study indicates that disparities in dentition
      associated with race/ethnicity, education and income still exist among adults in
      the USA. The results also indicate that to improve overall oral health and close
      the existing gaps in oral health, increased access to dental care would be needed
      for people who have low incomes and low levels of education.

PMID- 24117173
TI  - Two-stage hierarchical group testing for multiple infections with application to
      the infertility prevention project.
AB  - Screening for sexually transmitted diseases (STDs) has benefited greatly from the
      use of group testing (pooled testing) to lower costs. With the development of
      assays that detect multiple infections, screening practices now involve testing
      pools of individuals for multiple infections simultaneously. Building on the
      research for single infection group testing procedures, we examine the
      performance of group testing for multiple infections. Our work is motivated by
      chlamydia and gonorrhea testing for the infertility prevention project (IPP), a
      national program in the United States. We consider a two-stage pooling algorithm
      currently used to perform testing for the IPP. We first derive the operating
      characteristics of this algorithm for classification purposes (e.g., expected
      number of tests, misclassification probabilities, etc.) and identify pool sizes
      that minimize the expected number of tests. We then develop an expectation
      maximization (EM) algorithm to estimate probabilities of infection using both
      group and individual retest responses. Our research shows that group testing can
      offer large cost savings when classifying individuals for multiple infections and
      can provide prevalence estimates that are actually more efficient than those from
      individual testing. 

PMID- 24117175
TI  - Preparation and optimization of silver nanoparticles embedded electrospun
      membrane for implant associated infections prevention.
AB  - A strategy of using silver nanoparticle (AgNP)-loaded electrospun membrane as a
      novel coating material for preventing implant associated infections is reported.
      The strategy takes both the advantages of the excellent antibacterial as well as
      no drug resistance properties of AgNPs, and the widely used biodegradable
      electrospun membrane to serve as AgNP carrier and physical obstruction of
      bacteria adhesion. However, AgNPs have not been applied in clinical treatment yet
      because the concern of the potential toxicity. For the first time, we
      systematically investigated toxicity of AgNP-based coating materials in vitro and
      in vivo. Three dosages (0.1, 0.5, and 1.0 wt %) of silver nanoparticles (AgNPs)
      were embedded in biodegradable PLGA electrospun membranes as treatment devices to
      determine the precise concentration of AgNPs, minimize the dosage, and
      consequently reduced the toxicity in clinical applications. On the basis of
      antibacterial results and toxicity evaluations, PLGA electrospun membranes
      containing 0.5 wt % of AgNPs was considered as the most suitable combination,
      which is safe and effective for clinical application. 

PMID- 24117174
TI  - Thin polymer brush decouples biomaterial's micro-/nanotopology and stem cell
      adhesion.
AB  - Surface morphology and chemistry of polymers used as biomaterials, such as tissue
      engineering scaffolds, have a strong influence on the adhesion and behavior of
      human mesenchymal stem cells. Here we studied semicrystalline poly(epsilon
      caprolactone) (PCL) substrate scaffolds, which exhibited a variation of surface
      morphologies and roughness originating from different spherulitic
      superstructures. Substrates were obtained by varying the parameters of the
      thermal processing, that is, crystallization conditions. The cells attached to
      these polymer substrates adopted different morphologies responding to variations
      in spherulite density and size. In order to decouple substrate topology effects
      on the cells, sub-100 nm bioadhesive polymer brush coatings of oligo(ethylene
      glycol) methacrylates were grafted from PCL and functionalized with fibronectin.
      On surfaces featuring different surface textures, dense and sub-100 nm thick
      brush coatings determined the response of cells, irrespective to the underlying
      topology. Thus, polymer brushes decouple substrate micro-/nanoscale surface
      topology and the adhesion of stem cells. 

PMID- 24117176
TI  - Anxiety and sense of coherence in Roma and non-Roma coronary heart disease
      patients.
AB  - OBJECTIVE: Morbidity and mortality among Roma due to coronary heart disease (CHD)
      is high, but evidence on potential psychosocial pathways is lacking. This study
      aimed to assess the differences in the severity of anxiety symptoms and in the
      sense of coherence (SOC) between Roma and non-Roma CHD patients, crude and
      adjusted for age, sex, functional status and socio-economic status (SES). DESIGN:
      We examined 607 CHD patients (mean age 58.0 +/- 7.4, 28.7% female) scheduled for
      coronary angiography, 98 (16.1%) of whom were Roma. Anxiety symptoms were
      measured using the Hospital Anxiety and Depression Scale and SOC using the 13
      item Orientation to Life Questionnaire. Data were analysed using hierarchical
      regression. RESULTS: Roma ethnicity was associated with more severe anxiety (B =
      1.89; [95% confidence interval (CI) = 0.79; 2.98]) adjusted for age, sex,
      functional status and SES. Roma ethnicity was also associated with lower SOC (B =
      -4.77; [95% CI = -7.85; -1.68]) adjusted for age, sex and functional status. The
      latter association lost statistical significance after adjustment for SES.
      CONCLUSION: Roma ethnicity is associated with more anxiety symptoms and lower SOC
      among CHD patients. Our findings indicate that Roma CHD patients have a worse
      position regarding psychosocial factors that increase mortality and thus require
      additional attention.

PMID- 24117177
TI  - Extended interaction network of procollagen C-proteinase enhancer-1 in the
      extracellular matrix.
AB  - PCPE-1 (procollagen C-proteinase enhancer-1) is an extracellular matrix
      glycoprotein that can stimulate procollagen processing by procollagen C
      proteinases such as BMP-1 (bone morphogenetic protein 1). PCPE-1 interacts with
      several proteins in addition to procollagens and BMP-1, suggesting that it could
      be involved in biological processes other than collagen maturation. We thus
      searched for additional partners of PCPE-1 in the extracellular matrix, which
      could provide new insights into its biological roles. We identified 17 new
      partners of PCPE-1 by SPR (surface plasmon resonance) imaging. PCPE-1 forms a
      transient complex with the beta-amyloid peptide, whereas it forms high or very
      high affinity complexes with laminin-111 (KD=58.8 pM), collagen VI (KD=9.5 nM),
      TSP-1 (thrombospondin-1) (KD1=19.9 pM, KD2=14.5 nM), collagen IV (KD=49.4 nM) and
      endostatin, a fragment of collagen XVIII (KD1=0.30 nM, KD2=1.1 nM). Endostatin
      binds to the NTR (netrin-like) domain of PCPE-1 and decreases the degree of
      superstimulation of PCPE-1 enhancing activity by heparin. The analysis of the
      PCPE-1 interaction network based on Gene Ontology terms suggests that, besides
      its role in collagen deposition, PCPE-1 might be involved in tumour growth,
      neurodegenerative diseases and angiogenesis. In vitro assays have indeed shown
      that the CUB1CUB2 (where CUB is complement protein subcomponents C1r/C1s, urchin
      embryonic growth factor and BMP-1) fragment of PCPE-1 inhibits angiogenesis.

PMID- 24117178
TI  - Familial mediterranean fever: a fascinating model of inherited autoinflammatory
      disorder.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is a rare inherited autosomal
      recessive autoinflammatory disorder characterized by recurrent and self-limited
      episodes of fever and painful serositis, lasting 1-3 days. FMF occurs almost
      exclusively among ethnic groups of the Mediterranean basin, although cases have
      also been found in Japan and Korean populations. Diagnosis is based on clinical
      features, response to colchicine and genetic analysis. Novel drugs are emerging,
      allowing better management of colchicine-resistant/colchicine-intolerant
      patients. This review aims to attract the attention of the readers on
      differential diagnosis and management of patients with FMF. METHODS: The current
      state-of-the-art on FMF is outlined, with respect to epidemiological, genetic,
      pathophysiological and therapeutic characteristics, based on critical analysis of
      solid scientific literature. RESULTS: FMF is more frequent than it was thought
      before. The phenotypic expression of M694V is more severe than that of V726A.
      Patients with M694V/M694V homozygosity are exposed to a higher risk of developing
      renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and
      more frequent painful attacks. Life-long therapy with colchicine (1.0-2.4 mg/day)
      is effective and safe to prevent recurrent attacks and renal amyloidosis and to
      reverse proteinuria. In nonresponder patients, alternative novel approaches
      include interleukin-1 receptor antagonist anakinra and the interleukin-1 decoy
      receptor rilonacept. CONCLUSIONS: The prognosis of FMF is normal if AA
      amyloidosis is prevented. Colchicine remains the first-line therapy to treat pain
      and prevent amyloidosis. A follow-up should include clinical evaluation,
      therapeutic adjustments, measurement of serum amyloid A and proteinuria.

PMID- 24117179
TI  - Predictors of seizure-free outcome after epilepsy surgery for pediatric tuberous
      sclerosis complex.
AB  - PURPOSE: Variable predictors of postsurgical seizure outcome have been reported
      in children with tuberous sclerosis complex (TSC). We analyzed a large surgical
      series of pediatric TSC patients in order to identify prognostic factors crucial
      for selection of subjects for epilepsy surgery. METHODS: Thirty-three children
      with TSC who underwent excisional epilepsy surgery at Miami Children's Hospital
      were retrospectively reviewed. A total of 29 clinical, neuropsychological,
      electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical
      variables were analyzed and related to seizure outcomes. Univariate Barnard's
      exact test, Wilcoxon's rank-sum test, and multivariate statistical Cox's model
      were used to examine the significance of associations between the variables and
      seizure outcome. KEY FINDINGS: Eighteen patients (55%) have been seizure-free 2
      years after (final) surgery; postoperative complications occurred in five
      subjects (15%). Complete removal of epileptogenic tissue detected by both MRI and
      intracranial EEG, regional scalp interictal EEG patterns, and agreement of
      interictal and ictal EEG localization were the most powerful predictors of
      seizure-free outcome. Other significant predictors included occurrence of
      regional scalp ictal EEG patterns, fewer brain regions affected by tubers,
      presence of preoperative hemiparesis, and one-stage surgery. Remaining factors
      such as age at seizure onset, incidence of infantile spasms or other seizure
      types, duration of epilepsy, seizure frequency, mental retardation, as well as
      types and extent of resections did not influence outcome. SIGNIFICANCE:
      Perioperative features rather than preoperative variables are the most important
      determinants of postsurgical seizure outcome in patients with TSC. Our findings
      may assist in the surgical management of these patients.

PMID- 24117180
TI  - Physicochemical and thermodynamic characterization of the encapsulation of methyl
      jasmonate by natural and modified cyclodextrins using reversed-phase high
      pressure liquid chromatography.
AB  - Although the combinations of methyl jasmonate (MeJA) and cyclodextrins (CDs) have
      been used by different authors to stimulate the production of several
      metabolites, no study has been published about the possible formation of MeJA-CD
      complexes when these two molecules are added together to the reaction medium as
      elicitors. For this reason and because knowledge of the possible complexation
      process of MeJA with CD under different physicochemical conditions is essential
      if these two molecules are to be used in cell cultures, this paper looks at the
      complexation of MeJA with natural and modified CDs using a reversed-phase high
      pressure liquid chromatography (RP-HPLC) system. The interaction of MeJA with
      beta-CD was more efficient than with alpha- and gamma-CDs. However, a modified
      CD, HP-beta-CD, was the most effective of all of the CDs tested. Moreover, MeJA
      formed complexes with CD with a 1:1 stoichiometry, and the formation constants of
      these complexes were strongly dependent upon the temperature of the mobile phase
      used but not the pH. To obtain information about the mechanism of the affinity of
      MeJA for CD, the thermodynamic parameters DeltaG degrees , DeltaH degrees , and
      DeltaS degrees  were calculated. Finally, molecular modeling studies were carried
      out to propose which molecular interactions are established in the complexation
      process. 

PMID- 24117182
TI  - A unique case of phakomatosis pigmentovascularis.

PMID- 24117183
TI  - Influence of vitamin D mushroom powder supplementation on exercise-induced muscle
      damage in vitamin D insufficient high school athletes.
AB  - Incidence of vitamin D deficiency is increasing worldwide. The purpose of this
      study was to determine if supplementation with vitamin D2 from Portobello
      mushroom powder would enhance skeletal muscle function and attenuate exercise
      induced muscle damage in low vitamin D status high school athletes. Participants
      were randomised to Portobello mushroom powder (600 IU/d vitamin D2) or placebo
      for 6 weeks. Participants then completed a 1.5-h exercise session designed to
      induce skeletal muscle damage. Blood samples and measures of skeletal muscle
      function were taken pre-supplementation, post-supplementation/pre-exercise and
      post-exercise. Six weeks supplementation with vitamin D2 increased serum 25(OH)D2
      by 9.9-fold and decreased serum 25(OH)D3 by 28%. Changes in skeletal muscle
      function and circulating markers of skeletal muscle damage did not differ between
      groups. In conclusion, 600 IU/d vitamin D2 increased 25(OH)D2 with a concomitant
      decrease in 25(OD)D3, with no effect on muscular function or exercise-induced
      muscle damage in high school athletes.

PMID- 24117184
TI  - Genetic variability of Echinococcus granulosus based on the mitochondrial 16S
      ribosomal RNA gene.
AB  - Echinococcus granulosus is the etiological agent of cystic echinococcosis, a
      major zoonotic disease of both humans and animals. In this study, we assessed
      genetic variability and genetic structure of E. granulosus in the Tibet plateau,
      using the complete mitochondrial 16 S ribosomal RNA gene for the first time. We
      collected and sequenced 62 isolates of E. granulosus from 3 populations in the
      Tibet plateau. A BLAST analysis indicated that 61 isolates belonged to E.
      granulosus sensu stricto (genotypes G1-G3), while one isolate belonged to E.
      canadensis (genotype G6). We detected 16 haplotypes with a haplotype network
      revealing a star-like expansion, with the most common haplotype occupying the
      center of the network. Haplotype diversity and nucleotide diversity were low,
      while negative values were observed for Tajima's D and Fu's Fs. AMOVA results and
      Fst values revealed that the three geographic populations were not genetically
      differentiated. Our results suggest that a population bottleneck or population
      expansion has occurred in the past, and that this explains the low genetic
      variability of E. granulosus in the Tibet Plateau. 

PMID- 24117185
TI  - Live sharksucker Echeneis naucrates (Linnaeus 1758) mitochondrial genome: the
      first report of Echeneidae complete mitochondrial genome.
AB  - The complete mitochondrial genome of Echeneis naucrates is 16,611 bp in length.
      It comprises a control region, 13 protein-coding genes, 2 ribosomal RNAs (rRNAs)
      and 22 transfer RNAs (tRNAs), with an arrangement typical of vertebrate
      mitochondrial genomes. Base composition on the heavy strand is 30.24% A, 25.45%
      C, 15.02% G and 29.29% T. The control region is 940 bp in length, containing
      putative termination associated sequences (TASs) and conserved sequence blocks
      (CSBs). Two copies of a tandem repeat (AATATTAT) were found in all six
      individuals investigated. The hypothesis of selection for an optimal number of
      repeats as well as the evolutionary dynamics of tandem repeats in E. naucrates
      control regions await further investigations.

PMID- 24117186
TI  - The complete mitochondrial genome of the sea carp, Cyprinus acutidorsalis
      (Cypriniformes: Cyprinidae).
AB  - The complete mitochondrial genome of sea carp Cyprinus acutidorsalis was
      determined in this study. The genome was 16,579 bp in length. As in other
      vertebrates, it consisted of 13 protein-coding genes, 22 transfer RNA (tRNA)
      genes, 2 ribosomal RNA (rRNA) genes, and 1 non-coding control region. The overall
      base composition was estimated to be A, 31.9%; T, 24.8%; C, 27.6% and G, 15.7%
      with AT bias of 56.7%. The genomic composition, organization, and gene order of
      C. acutidorsalis was similar to most of vertebrates. This result may provide the
      basis for the study of genetic structure as well as resource conservation and
      protection of C. acutidorsalis.

PMID- 24117181
TI  - Unravelling mitochondrial pathways to Parkinson's disease.
AB  - Mitochondria are essential for cellular function due to their role in ATP
      production, calcium homeostasis and apoptotic signalling. Neurons are heavily
      reliant on mitochondrial integrity for their complex signalling, plasticity and
      excitability properties, and to ensure cell survival over decades. The
      maintenance of a pool of healthy mitochondria that can meet the bioenergetic
      demands of a neuron, is therefore of critical importance; this is achieved by
      maintaining a careful balance between mitochondrial biogenesis, mitochondrial
      trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that
      underlie these processes are gradually being elucidated. It is widely recognized
      that mitochondrial dysfunction occurs in many neurodegenerative diseases,
      including Parkinson's disease. Mitochondrial dysfunction in the form of reduced
      bioenergetic capacity, increased oxidative stress and reduced resistance to
      stress, is observed in several Parkinson's disease models. However,
      identification of the recessive genes implicated in Parkinson's disease has
      revealed a common pathway involving mitochondrial dynamics, transport, turnover
      and mitophagy. This body of work has led to the hypothesis that the homeostatic
      mechanisms that ensure a healthy mitochondrial pool are key to neuronal function
      and integrity. In this paradigm, impaired mitochondrial dynamics and clearance
      result in the accumulation of damaged and dysfunctional mitochondria, which may
      directly induce neuronal dysfunction and death. In this review, we consider the
      mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In
      particular, we focus on the mechanisms that underlie mitochondrial homeostasis,
      and discuss their importance in neuronal integrity and neurodegeneration in
      Parkinson's disease.

PMID- 24117187
TI  - Population genetic structure and larval dispersal strategy of portunid crab
      Charybdis bimaculata in Yellow sea and East China sea.
AB  - Larval dispersal may have an important effect on genetic structure of benthic
      species. However, different species may choose different larval dispersal
      strategy. To examine the population genetic structure and larval dispersal
      strategy of portunid crab Charybdis bimaculata, a 658 base pair (bp) fragment of
      mtDNA COI gene was sequenced in this species. In total, 67 individuals were
      collected from 5 locations in Yellow Sea and East China, and 24 haplotypes were
      obtained. Mean haplotype diversity and nucleotide diversity for the five
      populations ranged from 0.2000 +/- 0.1541 (Zhoushan) to 0.8333 +/- 0.1265 (Nanji
      island), and from 0.0003 +/- 0.0005 (Zhoushan) to 0.0026 +/- 0.0019 (Nanji
      island). Analysis of molecular variance and pairwise FST revealed no significant
      differentiation between the Yellow Sea and the East China Sea in C. bimaculata,
      supporting high larval dispersal ability in this species, rejecting larval
      retention. Mismatch distribution revealed that C. bimaculata had undergone
      population expansion. Larval drift in the ocean currents, and recent range
      expansion could be the reasons for little genetic structure in the studied area. 

PMID- 24117188
TI  - Association of mitochondrial DNA displacement loop polymorphisms and aggressive
      periodontitis in a Chinese population: a pilot study.
AB  - To examine whether certain mitochondrial DNA (mtDNA) haplogroups and/or
      alterations affect susceptibility to aggressive periodontitis (AgP), we analyzed
      the mtDNA D-Loop region in a Han Chinese population. The mtDNA haplogroups were
      analyzed in 58 patients with AgP and 50 periodontally healthy controls. The
      frequency of haplogroups A in AgP group was significantly higher than that in the
      control group (p=0.007). Furthermore, the frequency of haplogroup D was higher in
      the control group than that in AgP group (p=0.007). The frequencies of D-Loop
      polymorphisms m.16126T>C, m.16290C>T and m.152 T> C were significantly higher in
      patients with AgP compared with controls (p=0.029, 0.014 and 0.022,
      respectively). Additionally, the frequencies of three other D-Loop polymorphisms,
      m.16223C>T m.489 T>C and m.515CA deletion (del) were significantly lower in
      patients with AgP compared with controls (p=0.042, 0.003 and 0.026,
      respectively). Our study showed for the first time, an association between AgP
      and mtDNA haplogroups. Haplogroups A was implicated as a risk factor for AgP,
      while haplogroups D exhibited a protective effect in this disease. These
      observations may provide a new perspective on the study of the pathogenesis of
      periodontitis.

PMID- 24117189
TI  - Blood from a turnip: tissue origin of low-coverage shotgun sequencing libraries
      affects recovery of mitogenome sequences.
AB  - Next generation sequencing methods allow rapid, economical accumulation of data
      that have many applications, even at relatively low levels of genome coverage.
      However, the utility of shotgun sequencing data sets for specific goals may vary
      depending on the biological nature of the samples sequenced. We show that the
      ability to assemble mitogenomes from three avian samples of two different tissue
      types varies widely. In particular, data with coverage typical of microsatellite
      development efforts (~1*) from DNA extracted from avian blood failed to cover
      even 50% of the mitogenome, relative to at least 500-fold coverage from muscle
      derived data. Researchers should consider possible applications of their data and
      select the tissue source for their work accordingly. Practitioners analyzing low
      coverage shotgun sequencing data (including for microsatellite locus development)
      should consider the potential benefits of mitogenome assembly, including internal
      barcode verification of species identity, mitochondrial primer development, and
      phylogenetics. 

PMID- 24117190
TI  - The complete mitochondrial genome of natural Misgurnus bipartitus (Cypriniformes:
      Cobitidae).
AB  - Misgurnus bipartitus, a small sized freshwater fish species, is one of the most
      important cultured fish in East Asia. In this study, the complete mitochondrial
      genome of M. bipartitus is sequenced to be 16,636 bp in length, including 13
      protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, a control region and
      the origin of the light strand replication. The overall base composition of M.
      bipartitus in descending order is A 29.79%, T 27.95%, C 25.90% and G 16.36%, with
      a slight A + T bias. The mitogenome sequence data may provide useful information
      to the population genetics analysis of M. bipartitus and the elucidation of
      evolutionary mechanisms in Cobitidae.

PMID- 24117191
TI  - Complete mitochondrial genome of the desert toad-headed agama, Phrynocephalus
      przewalskii (Reptilia, Squamata, Agamidae), a novel gene organization in
      vertebrate mtDNA.
AB  - The mitogenome of the desert toad-headed agama, Phrynocephalus przewalskii, was
      amplified using polymerase chain reaction (PCR), long-and-accurate PCR and
      directly sequenced by primer walking. The complete mitogenome was 16,892 bp in
      size and contained 13 protein-coding, 23 tRNA, and 2 rRNA genes, and 1 control
      region. The mitogenome of the P. przewalskii was similar to those of other
      Phrynocephalus sand lizards in gene arrangement and composition, except that tRNA
      Phe and tRNA-Pro were exchanged and tRNA-Phe had two copies. The control region
      comprised three parts, one between tRNA-Thr and tRNA-Phe, a second between the
      two tRNA-Phe copies, and a third between tRNA-Pro and 12S RNA. The overall
      nucleotide composition of the H-strand was 36.3% A, 26.7% T, 12.5% G, 24.6% C.
      The complete mitogenome of P. przewalskii will contribute to understanding the
      evolution of the genus Phrynocephalus and the family Agamidae.

PMID- 24117192
TI  - Cognitive impairment in early-stage non-demented Parkinson's disease patients.
AB  - OBJECTIVES: In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and
      Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a
      risk factor for developing PDD. Knowledge of cognition in early-stages PD is
      essential in understanding and predicting the dementia process. MATERIALS AND
      METHODS: We describe the cognitive profile in early-stage PD patients with no
      prior clinical suspicion of cognitive impairment, depression or psychiatric
      disturbances, and investigate possible features distinguishing patients with
      cognitive deficits, defining a PD-MCI risk-profile. Single Photon Emission
      Computerized Tomography (SPECT) DaT-scan and neurological examination confirmed
      the diagnosis. Mini-mental state examination-, Addenbrooke's Cognitive
      Examination, Unified Parkinson's Disease Rating Scale scoring, Hoehn
      &Yahr/Activity of Daily Living staging and a neuropsychological test battery were
      applied. Mild cognitive impairment patients were identified according to modified
      criteria by Troster necessarily omitting subjective cognitive complaints. 80
      patients, mean age 61.0 years (SD 6.6), mean duration of disease 3.4 years (SD
      1.2) were included. 76 patients were neuropsychologically tested. RESULTS: 26
      (34%) patients fulfilled modified PD-MCI criteria, 18 (69%) of these showed
      episodic memory deficits, 14 (54%) executive dysfunction, 13 (50%)
      language/praxis deficits, 12 (46%) visuospatial/constructional deficits and 9
      (35%) attention/working memory deficits. Cognitive impairment was associated with
      higher Unified Parkinson's Disease Rating scale (UPDRS)-, bradykinesia- and
      rigidity scores and more symmetric distribution of symptoms, but not tremor
      scores. Patients with cognitive impairment were less educated. Other demographic
      and clinical variables were comparable. CONCLUSIONS: 34% of early-stage PD
      patients without prior clinical suspicion of cognitive impairment exhibit
      cognitive impairment, which is associated to disease severity, especially
      bradykinesia, rigidity, axial symptoms and less asymmetry of motor symptoms, even
      at early disease stages and when cognitive symptoms are mild.

PMID- 24117193
TI  - Physiosomatic complaints, immune-inflammatory pathways, and serotonin-related
      mood symptoms: relevance for tryptophan-related challenge procedures and clinical
      considerations with respect to the DSM-V.

PMID- 24117195
TI  - Beware of hidden trains: simultaneous discovery of a MYH9-related disease and
      chronic lymphocytic leukaemia.

PMID- 24117194
TI  - DNA methylation modulates HRES1/p28 expression in B cells from patients with
      Lupus.
AB  - Systemic lupus erythematosus (SLE) disease is an autoimmune disease of unknown
      aetiology that affects predominantly women of child bearing age. Since previous
      studies, including ours, have demonstrated that CD4+ T cells and B cells from SLE
      patients are defective in their ability to methylate their DNA upon antigen
      stimulation, the aim of this study was to investigate whether DNA demethylation
      affects the transcription of HRES-1 in B cells. HRES-1 is the prototype of Human
      Endogenous Retrovirus (HERV) overexpressed in SLE. We have observed that SLE B
      cells were characterized by their incapacity to methylate the HRES-1 promoter,
      both in unstimulated and in anti-IgM stimulated B cells. In turn, HRES-1/p28
      expression was increased in SLE B cells after B cell receptor engagement, but not
      in controls. In SLE B cells the Erk/DNMT1 pathway was defective. In addition,
      blocking the autocrine-loop of IL-6 in SLE B cells with an anti-IL-6 receptor
      monoclonal antibody restores DNA methylation and control of HRES-1/p28 expression
      became effective. As a consequence, a better understanding of HERV dysregulation
      in SLE reinforces our comprehension of the disease and opens new therapeutic
      perspectives.

PMID- 24117196
TI  - The opioid methadone induces a local anaesthetic-like inhibition of the cardiac
      Na+ channel, Na(v)1.5.
AB  - BACKGROUND AND PURPOSE: Treatment with methadone is associated with severe
      cardiac arrhythmias, a side effect that seems to result from an inhibition of
      cardiac hERG K+ channels. However, several other opioids are inhibitors of
      voltage-gated Na+ channels. Considering the common assumption that an inhibition
      of the cardiac Na+ channel Na(v)1.5, is the primary mechanism for local
      anaesthetic (LA)-induced cardiotoxicity, we hypothesized that methadone has LA
      like properties leading to a modulation of Na(v)1.5 channels. EXPERIMENTAL
      APPROACH: The whole-cell patch clamp technique was applied to investigate the
      effects of methadone on wild-type and mutant human Na(v)1.5 channels expressed in
      HEK293 cells. A homology model of human Na(v)1.5 channels was used to perform
      automated ligand-docking studies. KEY RESULTS: Methadone inhibited Na(v)1.5
      channels in a state-dependent manner, that is, tonic block was stronger with
      inactivated channels than with resting channels and a use-dependent block at 10
      Hz. Methadone induced a concentration-dependent shift of the voltage dependency
      of both fast and slow inactivation towards more hyperpolarized potentials, and
      impaired recovery from fast and slow inactivation. The LA-insensitive mutants
      N406K and F1760A exhibited reduced tonic and use-dependent block by methadone,
      and docking predictions positioned methadone in a cavity that was delimited by
      the residue F1760. Dextromethadone and levomethadone induced discrete stereo
      selective effects on Na(v)1.5 channels. CONCLUSIONS AND IMPLICATIONS: Methadone
      interacted with the LA-binding site to inhibit Na(v)1.5 channels. Our data
      suggest that these channels are a hitherto unrecognized molecular component
      contributing to cardiac arrhythmias induced by methadone.

PMID- 24117197
TI  - Laminated paper-based analytical devices (LPAD) with origami-enabled
      chemiluminescence immunoassay for cotinine detection in mouse serum.
AB  - Laminated paper-based analytical devices (LPAD) with origami-enabled
      chemiluminescence immunoassay have been developed for the detection of cotinine,
      a secondhand smoke (SHS) biomarker. The devices were fabricated by a craft-cutter
      to define flow channels, followed by lamination. This approach of
      cutting/lamination to fabricate LPAD is very similar to making an identification
      card, offering advantages in simplicity and rugged backing when compared to the
      common method of patterning paper using SU-8 or wax. We also developed a protocol
      of localized incision and paper-folding to isolate the detection zone from flow
      channels; the simple origami step eliminated possible reagent diffusion and flow
      during antibody immobilization steps and numerous washings. By incorporating
      luminol-based chemiluminescence for detecting horseradish peroxidase-conjugated
      cotinine, we employed origami-enabled LPAD to detect cotinine in mouse serum
      using competitive immunoassay. The detection limit was determined to be 5 ng/mL,
      a clinically relevant concentration. We believe that LPAD with chemiluminescence
      detection provides a new platform of low cost and sensitive assays for cotinine
      detection. 

PMID- 24117198
TI  - Amylin: what might be its role in Alzheimer's disease and how could this affect
      therapy?

PMID- 24117200
TI  - Update in research and methods in proteomics and bioinformatics.
AB  - The 3rd International Conference on Proteomics & Bioinformatics (Proteomics 2013)
      Philadelphia, PA, USA, 15-17 July 2013 The Third International Conference on
      Proteomics & Bioinformatics (Proteomics 2013) was sponsored by the OMICS group
      and was organized in order to strengthen the future of proteomics science by
      bringing together professionals, researchers and scholars from leading
      universities across the globe. The main topics of this conference included the
      integration of novel platforms in data analysis, the use of a systems biology
      approach, different novel mass spectrometry platforms and biomarker discovery
      methods. The conference was divided into proteomic methods and research
      interests. Among these two categories, interactions between methods in proteomics
      and bioinformatics, as well as other research methodologies, were discussed.
      Exceptional topics from the keynote forum, oral presentations and the poster
      session have been highlighted. The topics range from new techniques for analyzing
      proteomics data, to new models designed to help better understand genetic
      variations to the differences in the salivary proteomes of HIV-infected patients.

PMID- 24117201
TI  - Proteomic identification of protease cleavage sites: cell-biological and
      biomedical applications.
AB  - Proteolysis shapes proteomes by protein degradation or restricted proteolysis,
      which generates stable cleavage products. Proteolytic (in-)activation of enzymes
      and cytokines is an essential aspect of the functional proteome status. Proteome
      wide identification and quantification of proteolytic processing is accessible by
      complementary techniques for the focused analysis of protein termini. These
      innovative strategies are now widely applied and have transformed protease
      research. Pioneering studies portrayed apoptotic and caspase-dependent cleavage
      events. Protease-centric investigations focused predominantly on matrix
      metalloproteinases (MMPs), granzymes and aspartyl and cysteine cathepsins. The
      first in vivo degradomic studies were performed with mice lacking either cysteine
      cathepsins or matrix metalloproteinases. Process-centric degradomic analyses
      investigated infectious processes and mitochondrial import. Peptidomic analyses
      yielded disease biomarkers representing cleavage fragments from bodily fluids.
      The diversity of degradomic endeavors illustrates the importance of portraying
      proteolytic processing in health and disease. The present review provides an
      overview of the current status of degradomic studies. 

PMID- 24117202
TI  - Atopic dermatitis-associated protein interaction network lead to new insights in
      chronic sulfur mustard skin lesion mechanisms.
AB  - Chronic sulfur mustard skin lesions (CSMSLs) are the most common complications of
      sulfur mustard exposure; however, its mechanism is not completely
      understood.According to clinical signs, there are similarities between CSMSL and
      atopic dermatitis (AD). In this study, proteomic results of AD were reviewed and
      the AD-associated protein-protein interaction network (PIN) was analyzed.
      According to centrality measurements, 16 proteins were designated as pivotal
      elements in AD mechanisms. Interestingly, most of these proteins had been
      reported in some sulfur mustard-related studies in late and acute phases
      separately. Based on the gene enrichment analysis, aging, cell response to
      stress, cancer, Toll- and NOD-like receptor and apoptosis signaling pathways have
      the greatest impact on the disease. By the analysis of directed protein
      interaction networks, it is concluded that TNF, IL-6, AKT1, NOS3 and CDKN1A are
      the most important proteins. It is possible that these proteins play role in the
      shared complications of AD and CSMSL including xerosis and itching.

PMID- 24117203
TI  - Proteomics strategies to analyze HPV-transformed cells: relevance to cervical
      cancer.
AB  - Cervical cancer is the second most common malignant tumor among women worldwide.
      The initiating event of cervical cancer is the infection with certain types of
      human papillomavirus (HPV). Interestingly, viral oncogene expression is necessary
      but not per se sufficient to promote cervical cancer and other factors are
      involved in neoplastic progression. Thus, major research efforts should be
      focused to identify novel co-carcinogenic factors and to understand the
      mechanisms played into tumor development. To reach this goal, proteomics
      strategies are powerful tools and a number of studies performed by following this
      approach have contributed to unravel the interplay between viral infection and
      protein dysfunction that ultimately results in cancer. The present review
      summarizes the most relevant findings obtained by applying proteomics
      technologies to both cell culture models and human tissue specimens. The results
      suggest that viral oncogenes selectively interact with a subset of intracellular
      proteins mainly involved in apoptosis resistance, cell growth and differentiation
      and cell transformation. 

PMID- 24117204
TI  - Proteomics and metabolomics in cancer drug development.
AB  - In this review article, the main recent advancements in the field of proteomics
      and metabolomics and their application in cancer research are described. In the
      second part of the review the main metabolic alterations observed in cancer cells
      are thoroughly dissected, especially those involving anabolic pathways and NADPH
      generating pathways, which indirectly affect anabolic reactions, other than the
      maintenance of the redox poise. Alterations to mitochondrial pathways and thereby
      deriving oncometabolites are also detailed. The third section of the review is a
      discussion of how and to what extent (mutations to) tumor suppressors and
      oncogenes end up influencing cancer cell metabolism and cell fate, either
      promoting survival and proliferation or autophagy and apoptosis. In the last
      section of the review, an overview is provided of therapeutic strategies that
      make use of metabolic reprogramming approaches. 

PMID- 24117205
TI  - The role of survivin in thyroid tumors: differences of expression in well
      differentiated, non-well-differentiated, and anaplastic thyroid cancers.
AB  - BACKGROUND: Survivin is involved in human cancer and is responsible for
      aggressive biological behavior and poor clinical outcomes in several human
      malignancies. Thus, we hypothesized that the upregulation of survivin protein
      expression may be enhanced in parallel with transition toward a poorly
      differentiated phenotype in human thyroid carcinomas. METHODS: The expression of
      survivin was evaluated, using a standard linked streptavidin-biotin horseradish
      peroxidase technique technique, in a series of 56 human thyroid carcinomas (42
      papillary, 4 poorly differentiated, and 10 anaplastic carcinomas) and thyroid
      carcinoma cell lines at different degrees of differentiation. RESULTS: The
      cytoplasmic expression of survivin protein was significantly upregulated in all
      thyroid tumors. A statistically significant association was found between nuclear
      survivin expression and anaplastic thyroid cancer (mean +/- SD: well
      differentiated thyroid cancer, 1.22 +/- 20.21; non-well-differentiated thyroid
      cancer, 34.00 +/- 25.17; anaplastic thyroid cancer, 56.50 +/- 22.10; p<0.001).
      Nuclear staining of survivin has been shown in poorly differentiated and
      anaplastic thyroid carcinomas, and this is likely due to the upregulation of the
      DeltaEx3 survivin splicing variant, as shown in poorly differentiated/anaplastic
      thyroid carcinoma cell lines. Of note, selected thyroid tumors characterized by a
      mixed population of differentiated and undifferentiated neoplastic cells, likely
      progressing from well to poorly differentiated and anaplastic phenotypes,
      exhibited cytoplasmic expression of survivin in differentiated fields and nuclear
      protein staining in poorly differentiated and anaplastic areas. This expression
      profile provides substantial added value to conventional clinical markers in
      predicting anaplastic cancer. The cut-off for distinguishing thyroids that
      developed ATC from those that remained differentiated was >30% of nuclear
      survivin expression. The receiver operating characteristic (ROC) area was 0.92,
      with a p-value of <0.0001. CONCLUSIONS: Upregulation of survivin expression may
      be a molecular marker of dedifferentiation in thyroid epithelial carcinomas,
      likely being responsible for survival responses of tumor cells and, thus,
      favoring progression toward a poorly differentiated phenotype.

PMID- 24117206
TI  - The alpha-effect in gas-phase SN2 reactions of microsolvated anions: methanol as
      a solvent.
AB  - The alpha-effect, an enhanced reactivity of nucleophiles with a lone-pair
      adjacent to the reaction center, has been studied in solution for several
      decades. The gas-phase alpha-effect has recently been documented in studies of
      SN2 reactions as well as in competing reactions for both bare and microhydrated
      anions. In the present work we extend our studies of the significance of
      microsolvation on the alpha-effect, employing methanol as the solvent, in the
      expectation that the greater stability of the methanol cluster relative to the
      water cluster will lower the reactivity and thereby allow studies over a wider
      efficiency range. We compare the gas-phase reactivity of the microsolvated alpha
      nucleophile HOO(-)(CH3OH) to that of microsolvated normal alkoxy nucleophiles,
      RO(-)(CH3OH) in reactions with CH3Cl and CH3Br. The results reveal enhanced
      reactivity of HOO(-)(CH3OH) toward both methyl halides relative to the normal
      nucleophiles, and clearly demonstrate the presence of an alpha-effect for the
      microsolvated alpha-nucleophile. The highly exothermic reactions with methyl
      bromide result in a smaller Bronsted betanuc value than observed for methyl
      chloride, and the alpha-effect in turn influences the reactions with methyl
      chloride more than with methyl bromide. Computational investigations reveal that
      reactions with methyl bromide proceed through earlier transition states with less
      advanced bond formation compared to the related reactions of methyl chloride. In
      addition, solvent interactions for HOO(-) are quite different from those with the
      normal nucleophiles at the transition state, indicating that differential
      solvation may well contribute to the alpha-effect. The greater thermodynamic and
      kinetic stability of the anion-methanol clusters relative to the anion-water
      clusters accounts well for the differences in the influence of solvation with the
      two protic polar solvents. 

PMID- 24117207
TI  - Access to indenones by rhodium(III)-catalyzed C-H annulation of arylnitrones with
      internal alkynes.
AB  - Under redox-neutral conditions, rhodium(III)-catalyzed C-H annulation of N-tert
      butyl-alpha-arylnitrones with internal alkynes has been realized for the
      synthesis of indenones under mild conditions. This reaction proceeded in moderate
      to high yields and with good functional group tolerance. 

PMID- 24117208
TI  - Spinel CuCo2O4 nanoparticles supported on N-doped reduced graphene oxide: a
      highly active and stable hybrid electrocatalyst for the oxygen reduction
      reaction.
AB  - In this Letter, for the first time, we demonstrated the preparation of a highly
      efficient electrocatalyst, spinel CuCo2O4 nanoparticles supported on N-doped
      reduced graphene oxide (CuCo2O4/N-rGO), for an oxygen reduction reaction (ORR)
      under alkaline media. The hybrid exhibits higher ORR catalytic activity than
      CuCo2O4 or N-rGO alone, the physical mixture of CuCo2O4 nanoparticles and N-rGO,
      and Co3O4/N-rGO. Moreover, such a hybrid affords superior durability to the
      commercial Pt/C catalyst. 

PMID- 24117209
TI  - Paliperidone palmitate long-acting injection--prospective year-long follow-up of
      use in clinical practice.
AB  - OBJECTIVE: To follow-up patients prescribed paliperidone palmitate long-acting
      injection (PP) over 1 year to determine factors predicting continuation with PP
      treatment. METHOD: Naturalistic observation of patients registered as starting PP
      in a single healthcare unit in London, UK. Monovariate and multivariate (Cox
      regression) analysis of factors predicting continuation at 1 year. RESULTS: Data
      were available for 210 patients consecutively prescribed PP of whom 10 were lost
      to follow-up. At 1 year, 65% of 200 patients (176 with a diagnosis of
      schizophrenia or schizoaffective disorder) started on PP were still receiving it.
      The main reason for discontinuation was perceived ineffectiveness (52% of
      discontinuers); only 10 subjects (5% of total) discontinued because of adverse
      effects. Initiation as an out-patient [hazard ratio (HR) 0.39, 95%CI, 0.20, 0.67,
      P = 0.001]; being switched from risperidone (HR 0.56, 95%CI 0.32, 0.94, P =
      0.026) and correct initiation (HR 0.56, 95%CI 0.34, 0.93, P = 0.024) were
      significantly associated with a lower likelihood of discontinuation. CONCLUSION:
      Paliperidone palmitate was effective and well tolerated in this naturalistic
      cohort. Optimising treatment by targeting PP for patients identified as having
      lower risk of discontinuation can give rise to continuation rates approaching 80%
      at 1 year.

PMID- 24117212
TI  - Perceptions of caring in China: patient and nurse questionnaire survey.
AB  - BACKGROUND: The concept of caring is important to both patients and nurses. If
      patients and nurses perceive caring behaviours differently, patients may not have
      their needs met or will be dissatisfied with the nursing. AIM: This study
      conducted in mainland China compared the perceptions of nurses and patients
      concerning nurses' caring behaviours. METHODS: From November 2011 to June 2012,
      680 patients and 540 of their nurses in five hospitals in southern, central and
      eastern China were invited to complete a descriptive comparative survey with four
      subcategories, the Caring Behaviors Inventory-24. Respondents scored each of the
      24 items on the survey from 1 (low) to 6 (high). Of those invited, 595 patients
      (87.50%) and 445 (82.41%) nurses completed the survey. RESULTS: The mean item
      score on the Caring Behaviors Inventory-24 was 4.32 and 4.96 for patients and
      nurses, respectively. The subcategory with the highest mean score for both groups
      was knowledge and skills (4.73, 5.25), and the lowest for both groups was
      positive connectedness (3.98, 4.51). Nurses' scores were significantly higher
      than those of patients for all four subcategories (P < 0.001). CONCLUSIONS: The
      gap between the two groups indicates that nurses need to improve their
      understanding and response to patients' actual and perceived needs and
      expectations. In China, patients require more support from nurses of their
      psychological needs. STUDY LIMITATIONS: Participants came from a limited number
      of hospitals in three cities. A larger sample from different hospitals in
      mainland China could have increased the power of the study.

PMID- 24117210
TI  - How I treat children and adolescents with acute promyelocytic leukaemia.
AB  - Acute promyelocytic leukaemia (APL) is a rare subtype of acute myeloid leukaemia.
      The outcome of paediatric APL has improved substantially over the past 20 years;
      cure rates above 80% are expected when all-trans retinoic acid (ATRA) is given
      with anthracycline-based regimens. The presenting features of paediatric APL may
      include severe bleeding and thrombotic complications, which contribute to the
      high early death rate. The incidence of leucocytosis and the microgranular
      subtype is greater in paediatric than adult APL, and children experience greater
      ATRA-related toxicity. It is crucial to begin ATRA therapy and intensive platelet
      and fibrinogen replacement on first suspicion of APL. Recent risk-adapted
      therapeutic trials have shown that patients at greater risk of relapse benefit
      from the introduction of high-dose cytarabine during consolidation. Combination
      therapy with ATRA and arsenic trioxide provides very effective frontline
      treatment and may reduce the need for subsequent anthracycline therapy. 

PMID- 24117213
TI  - In situ magnetic field-assisted low temperature atmospheric growth of GaN
      nanowires via the vapor-liquid-solid mechanism.
AB  - We report the growth of GaN nanowires at a low temperature of 750  degrees C and
      at atmospheric pressure in a conventional chemical vapor deposition (CVD) setup
      via the vapor-liquid-solid mechanism with remarkable control of directionality
      and growth behavior by using an in situ magnetic field. Under typical growth
      conditions, without any magnetic field, the nanowires are severely twisted and
      kinked, and exhibit a high density of planar stacking defects. With increasing in
      situ magnetic field strength, the microstructural defects are found to decrease
      progressively, and quasi-aligned nanowires are produced. At an applied magnetic
      field strength of 0.80 T, near-vertical aligned straight and several micrometers
      long nanowires of average diameter of ~40 nm with defect-free microstructure are
      routinely produced. Photoluminescence measurements show that the relative
      intensity of the defect-related peaks in the visible region with respect to the
      near-band-edge emission continuously decrease with increase in the applied in
      situ magnetic field strength, ascribable to the magnetic field-assisted
      significant structural improvement of the wires. It is found out that the degree
      of agglomerative Ni droplet on Si is critically influenced by the surface tension
      driven by the magnetic force, which in turn determines the eventual properties of
      the nanowires.

PMID- 24117211
TI  - Endgame: engaging the tobacco industry in its own elimination.
AB  - A billion deaths from tobacco are expected by 2100. Many policy interventions
      such as increased taxation, restrictions on advertisement, smoking bans, as well
      as behavioral interventions, such as pharmacological and psychological treatments
      for smoking cessation, decrease tobacco use, but they reach their limits. Endgame
      scenarios focusing on tobacco supply rather than demand are increasingly
      discussed, but meet with resistance by the industry and even by many tobacco
      control experts. A main stumbling block that requires more attention is what to
      do with the tobacco industry in endgame scenarios. This industry has employed
      notoriously talented experts in law, business, organization, marketing,
      advertising, strategy, policy, and statistics and has tremendous lobbying power.
      Performance-based regulatory approaches can pose a legal obligation on
      manufacturers to decrease - and eventually - eliminate tobacco products according
      to specified schedules. Penalties and rewards can make such plans both beneficial
      for public health and attractive to the companies that do the job well. We
      discuss caveats and reality checks of engaging the tobacco industry to eliminate
      its current market and change focus. Brainstorming is warranted to entice the
      industry to abandon tobacco for other profit goals. To get the dialogue started,
      we propose the wild possibility of hiring former tobacco companies to reduce the
      costs of healthcare, thereby addressing concurrently two major challenges to
      public health. 

PMID- 24117214
TI  - Understanding family health information seeking: a test of the theory of
      motivated information management.
AB  - Although a family health history can be used to assess disease risk and increase
      health prevention behaviors, research suggests that few people have collected
      family health information. Guided by the Theory of Motivated Information
      Management, this study seeks to understand the barriers to and facilitators of
      interpersonal information seeking about family health history. Individuals who
      were engaged to be married (N = 306) were surveyed online and in person to
      understand how factors such as uncertainty, expectations for an information
      search, efficacy, and anxiety influence decisions and strategies for obtaining
      family health histories. The results supported the Theory of Motivated
      Information Management by demonstrating that individuals who experienced
      uncertainty discrepancies regarding family heath history had greater intention to
      seek information from family members when anxiety was low, outcome expectancy was
      high, and communication efficacy was positive. Although raising uncertainty about
      family health history may be an effective tool for health communicators to
      increase communication among family members, low-anxiety situations may be
      optimal for information seeking. Health communication messages must also build
      confidence in people's ability to communicate with family to obtain the needed
      health information. 

PMID- 24117215
TI  - Palladium(II)-catalyzed oxidative arylation of quinoxalin-2(1H)-ones with
      arylboronic acids.
AB  - A straightforward palladium-catalyzed oxidative C-3 arylation of quinoxalin-2(1H)
      ones with arylboronic acids is reported. This protocol is compatible with a wide
      range of functional groups and allows construction of various biologically
      important quinoxalin-2(1H)-one backbones. 

PMID- 24117216
TI  - Hybrid pairwise likelihood analysis of animal behavior experiments.
AB  - The study of the determinants of fights between animals is an important issue in
      understanding animal behavior. For this purpose, tournament experiments among a
      set of animals are often used by zoologists. The results of these tournament
      experiments are naturally analyzed by paired comparison models. Proper
      statistical analysis of these models is complicated by the presence of dependence
      between the outcomes of fights because the same animal is involved in different
      contests. This paper discusses two different model specifications to account for
      between-fights dependence. Models are fitted through the hybrid pairwise
      likelihood method that iterates between optimal estimating equations for the
      regression parameters and pairwise likelihood inference for the association
      parameters. This approach requires the specification of means and covariances
      only. For this reason, the method can be applied also when the computation of the
      joint distribution is difficult or inconvenient. The proposed methodology is
      investigated by simulation studies and applied to real data about adult male Cape
      Dwarf Chameleons. 

PMID- 24117217
TI  - The miR-19a/b family positively regulates cardiomyocyte hypertrophy by targeting
      atrogin-1 and MuRF-1.
AB  - Progressive cardiac hypertrophy owing to pathological stimuli, such as pressure
      overload, is frequently associated with the development of heart failure, a major
      cause of morbidity and mortality worldwide. Growing evidence has shown that
      miRNAs are extensively involved in the pathogenesis of cardiac hypertrophy. In
      the present study, we examined the hypothesis that the miR-19a/b family acts as a
      key regulator of cardiac hypertrophy and apoptosis. Forced overexpression of miR
      19a/b was sufficient to induce hypertrophy in rat neonatal cardiomyocytes.
      Luciferase assays revealed that miR-19a/b directly target the anti-hypertrophic
      genes atrogin-1 and MuRF-1 (muscle RING-finger protein-1). The endogenous
      expressions of the target genes were down-regulated by miR-19a/b. Pro
      hypertrophic calcineurin/NFAT (nuclear factor of activated T-cells) signalling
      was elevated markedly in the presence of miR-19b, and the calcineurin inhibitor
      CsA (cyclosporin A) and the PKC (protein kinase C) inhibitor GF10923X
      significantly attenuated the miR-19b-mediated increase in cell size and
      expression of hypertrophic markers. Furthermore, miR-19b led to increased cell
      survival through up-regulation of the NFAT target gene encoding alpha-crystallin
      B and repression of the pro-apoptotic gene Bim (Bcl-2-interacting mediator of
      cell death) under ER (endoplasmic reticulum) stress conditions. Taken together,
      the results of the present study demonstrate that the miR-19a/b family regulates
      phenotypes of cardiomyocytes via suppression of multiple direct target genes.

PMID- 24117218
TI  - Proposal for a magnetic resonance imaging protocol for the detection of
      epileptogenic lesions at early outpatient stages.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is a key technology in the presurgical
      evaluation of patients with epilepsy. Already at early outpatient stages it can
      contribute to the identification of patients who are, in the case of
      pharmacoresistance, good candidates for epilepsy surgery. Yet, "standard head"
      MRI examinations often fail to displaying therapeutically relevant epileptogenic
      lesions. The purpose of this study is to identify an epilepsy-specific MRI
      protocol, which is likewise sensitive for even small epileptogenic lesions and
      economical enough to be applied outside specialized epilepsy centers. METHODS:
      Based on a large European presurgical epilepsy program comprising 2,740 patients
      we identified the spectrum of common epileptogenic lesions and determine the set
      of MRI sequences that are required for their reliable detection. Relying on a
      series of small, therapeutically particularly relevant lesions we determined the
      required slices thickness, slice angulations, and orientations for an epilepsy
      specific MRI protocol. KEY FINDINGS: Indispensable for early outpatient epilepsy
      specific MRI are fluid attenuated inversion recovery (FLAIR), T(2) -weighted,
      T(1) -weighted, and hemosiderin/calcification-sensitive sequences. Slice
      thickness for T(2) and FLAIR must not exceed 3 mm. The T(1) image should be
      acquired in three-dimensional technique at 1 mm isotropic voxels size. For T(2)
      and FLAIR, at least two slice orientations each must be demanded in hippocampal
      angulation. We suggest no adaption to a clinical focus hypothesis. The resulting
      "essential 6" sequence protocol allows the detection of virtually all common
      epileptogenic lesion entities. SIGNIFICANCE: The creation of a broadly accepted
      and abundantly applied MRI protocol for epilepsy outpatients can contribute to
      improved and earlier identification of potential candidates for epilepsy surgery.
      Our systematic analysis of MRI requirements for the detection of epileptogenic
      lesions can serve as basis for protocol negotiations between epileptologists,
      radiologists, and health care funders.

PMID- 24117219
TI  - New sesquiterpene lactones from sunflower root exudate as germination stimulants
      for Orobanche cumana.
AB  - Orobanche cumana is a serious threat for cultivation of sunflower in Europe and
      Asia. Germination of the parasite is induced by metabolites released from the
      host root system. The first germination stimulant from sunflower root exudate was
      recently identified as dehydrocostus lactone, a sesquiterpene lactone. Bioassay
      guided fractionation of root exudates now showed the release of additional
      sesquiterpene lactones. Besides dehydrocostus lactone, costunolide, tomentosin,
      and 8-epixanthatin were purified and identified spectroscopically. All four
      compounds induced germination of O. cumana at nano- to micromolar concentrations.
      Costunolide and dehydrocostus lactone concentrations above 1 MUM reduced the
      activity, and application of 100 MUM inhibited germination irreversibly. Seeds of
      Phelipanche ramosa could not be induced with costunolide. O. cumana seeds also
      germinated with GR24, a synthetic strigolactone. No bioactive fraction of
      sunflower contained compounds of this type. This supports previous findings that
      sesquiterpene lactones instead of strigolactones trigger the sunflower/O. cumana
      interaction. 

PMID- 24117220
TI  - Platelet P2Y12 receptors are involved in the haemostatic effect of
      notoginsenoside Ft1, a saponin isolated from Panax notoginseng.
AB  - BACKGROUND AND PURPOSE: Saponins isolated from Panax notoginseng (Burk.) F.H.
      Chen have been shown to relieve thrombogenesis and facilitate haemostasis.
      However, it is not known which saponin accounts for this haemostatic effect.
      Hence, in the present study we aimed to identify which saponins contribute to its
      haemostatic activity and to elucidate the possible underlying mechanisms.
      EXPERIMENTAL APPROACH: Platelet aggregation was analysed using a platelet
      aggregometer. Prothrombin time, activated partial thromboplastin time and
      thrombin time were measured using a blood coagulation analyser, which was further
      corroborated with bleeding time and thrombotic assays. The interaction of
      notoginsenoside Ft1 with the platelet P2Y12 receptor was determined by molecular
      docking analysis, cytosolic Ca(2+) and cAMP measurements, and phosphorylation of
      PI3K and Akt assays. KEY RESULTS: Among the saponins examined, Ft1 was the most
      potent procoagulant and induced dose-dependent platelet aggregation. Ft1 reduced
      plasma coagulation indexes, decreased tail bleeding time and increased
      thrombogenesis. Moreover, it potentiated ADP-induced platelet aggregation and
      increased cytosolic Ca(2+) accumulation, effects that were attenuated by
      clopidogrel. Molecular docking analysis suggested that Ft1 binds to platelet
      P2Y12 receptors. The increase in intracellular Ca(2+) evoked by Ft1 in HEK293
      cells overexpressing P2Y12 receptors could be blocked by ticagrelor. Ft1 also
      affected the production of cAMP and increased phosphorylation of PI3K and Akt
      downstream of P2Y12 signalling pathways. CONCLUSION AND IMPLICATIONS: Ft1
      enhanced platelet aggregation by activating a signalling network mediated through
      P2Y12 receptors. These novel findings may contribute to the effective utilization
      of this compound in the therapy of haematological disorders.

PMID- 24117221
TI  - Functional characterization of the Thr946Ala SNP at the type 1 diabetes IFIH1
      locus.
AB  - The Thr allele at the Thr946Ala non-synonymous single-nucleotide polymorphism
      (nsSNP) in the IFIH1 gene confers risk for type 1 diabetes (T1D). IFIH1 binds
      viral double-stranded RNA (dsRNA), inducing a type I interferon (IFN) response.
      Reports of this nsSNP's role in IFIH1 expression regulation have produced
      conflicting results and a study evaluating transfected Thr946Ala protein alleles
      in an artificial system overexpressing IFIH1 shows that the SNP does not affect
      IFH1 function. In this study, we examine the effects of the Thr946Ala
      polymorphism on IFN-alpha response in a cell line that endogenously expresses
      physiological levels of IFIH1. Eleven lymphoblastoid cell lines (LCLs) homozygous
      for the major predisposing allele (Thr/Thr) and 6 LCLs homozygous for the minor
      protective allele (Ala/Ala) were electroporated with the viral dsRNA mimic, poly
      I:C, in three independent experiments. Media were collected 24 hours later and
      measured for IFN-alpha production by ELISA. Basal IFN response is minimal in mock
      transfected cells from both genotypes and increases by about 8-fold in cells
      treated with poly I:C. LCLs with the Ala/Ala genotype have slightly higher IFN
      alpha levels than their Thr/Thr counterparts but this did not reach statistical
      significance because of the large variability of the IFN response, due mostly to
      two high outliers (biological, not technical). A larger sample size would be
      needed to determine whether the Thr946Ala SNP affects the poly I:C-driven IFN
      alpha response. Additionally, the possibility that this nsSNP recognizes viral
      dsRNA specificities cannot be ruled out. Thus, the mechanism of the observed
      association of this SNP with T1D remains to be determined.

PMID- 24117222
TI  - Accountable Care Organizations in the United States: market and demographic
      factors associated with formation.
AB  - BACKGROUND: The Accountable Care Organization (ACO) model is rapidly being
      implemented by Medicare, private payers, and states, but little is known about
      the scope of ACO implementation. OBJECTIVE: To determine the number of
      accountable care organizations in the United States, where they are located, and
      characteristics associated with ACO formation. STUDY DESIGN, METHODS, AND DATA:
      Cross-sectional study of all ACOs in the United States as of August 2012. We
      identified ACOs from multiple sources; documented service locations (practices,
      clinics, hospitals); and linked service locations to local areas, defined as
      Dartmouth Atlas hospital service areas. We used multivariate analysis to assess
      what characteristics were associated with local ACO presence. We examined
      demographic characteristics (2010 American Community Survey) and health care
      system characteristics (2010 Medicare fee-for-service claims data). PRINCIPAL
      FINDINGS: We identified 227 ACOs located in 27 percent of local areas. Fifty-five
      percent of the US population resides in these areas. HSA-level characteristics
      associated with ACO presence include higher performance on quality, higher
      Medicare per capita spending, fewer primary care physician groups, greater
      managed care penetration, lower poverty rates, and urban location. CONCLUSIONS:
      Much of the US population resides in areas where ACOs have been established. ACO
      formation has taken place where it may be easier to meet quality and cost
      targets. Wider adoption of the ACO model may require tailoring to local context.

PMID- 24117223
TI  - Label-free fluorometric method for monitoring conformational flexibility of
      laccase based on a selective laccase sensor.
AB  - A facile and selective fluorescence sensor for laccase determination has been
      proposed depending on the interaction between 3-azidocoumarin and trametes
      versicolor (Tv) laccase in this paper. The azido group of 3-azidocoumarin that is
      electron-rich alpha-nitrogen can directly interact with histidines that
      coordinate to three copper sites through hydrogen bonds and forms a new complex,
      which decreases the electron-donating ability of the azido group, leading to
      enhance the fluorescence intensity of the sensing system. Also, other common
      proteins have no significant interference for the proposed laccase sensor.
      Additionally, the proposed fluorescence sensor is extended to demonstrate the
      conformational flexibility of Tv laccase by the urea denaturant. A good
      consistency of the results obtained with the presented laccase sensor and CD
      spectra is performed. Furthermore, the relationship between the catalytic
      activity and the unfolding percentage of the unfolded Tv laccase through the
      proposed laccase sensor is also elucidated well. 

PMID- 24117224
TI  - Measurement of the dynamics in ski jumping using a wearable inertial sensor-based
      system.
AB  - Dynamics is a central aspect of ski jumping, particularly during take-off and
      stable flight. Currently, measurement systems able to measure ski jumping
      dynamics (e.g. 3D cameras, force plates) are complex and only available in few
      research centres worldwide. This study proposes a method to determine dynamics
      using a wearable inertial sensor-based system which can be used routinely on any
      ski jumping hill. The system automatically calculates characteristic dynamic
      parameters during take-off (position and velocity of the centre of mass
      perpendicular to the table, force acting on the centre of mass perpendicular to
      the table and somersault angular velocity) and stable flight (total aerodynamic
      force). Furthermore, the acceleration of the ski perpendicular to the table was
      quantified to characterise the skis lift at take-off. The system was tested with
      two groups of 11 athletes with different jump distances. The force acting on the
      centre of mass, acceleration of the ski perpendicular to the table, somersault
      angular velocity and total aerodynamic force were different between groups and
      correlated with the jump distances. Furthermore, all dynamic parameters were
      within the range of prior studies based on stationary measurement systems, except
      for the centre of mass mean force which was slightly lower.

PMID- 24117226
TI  - Herpes zoster duplex bilateralis symmetricus in an immunocompetent subject.

PMID- 24117225
TI  - Bupivacaine-induced cellular entry of QX-314 and its contribution to differential
      nerve block.
AB  - BACKGROUND AND PURPOSE: Selective nociceptor fibre block is achieved by
      introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl
      bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into
      nociceptors. We screened local anaesthetics for their capacity to activate TRP
      channels, and characterized the nerve block obtained by combination with QX-314.
      EXPERIMENTAL APPROACH: We investigated TRP channel activation in dorsal root
      ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and
      cellular QX-314 uptake by MS. To characterize nerve block, compound action
      potential (CAP) recordings from isolated nerves and behavioural responses were
      analysed. KEY RESULTS: Of the 12 compounds tested, bupivacaine was the most
      potent activator of ruthenium red-sensitive calcium entry in DRG neurons and
      activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1
      channels and accumulated intracellularly after activation of these channels. Upon
      sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and
      also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-,
      but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314.
      Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and
      TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry
      pathway. Consistent with this, high doses of bupivacaine promoted a non
      selective, cellular uptake of QX-314. CONCLUSIONS AND IMPLICATIONS: Bupivacaine,
      combined with QX-314, produced a long-lasting sensory nerve block. This did not
      require QX-314 permeation through TRPA1, although bupivacaine activated these
      channels. Regardless of entry pathway, the greatly extended duration of block
      produced by QX-314 and bupivacaine may be clinically useful.

PMID- 24117227
TI  - Pre- and post-operative dizziness and postural instability in temporal arachnoid
      cyst patients.
AB  - OBJECTIVES: Arachnoid cysts (AC) are benign, congenital malformations of the
      leptomeninges, with a predilection for the temporal fossa. In our clinical
      experience, patients with temporal AC often complain of dizziness and imbalance.
      However, these symptoms and the effect of surgery on them have not been studied
      before. MATERIALS AND METHODS: Dizziness and imbalance in patients with temporal
      AC were quantified before and after surgical cyst decompression, using the
      Dizziness Handicap Inventory (DHI), Vertigo Symptom Scale - Short-Form (VSS-SF)
      and computerized dynamic posturography (CDP). The study includes 16 patients with
      temporal AC and 15 control subjects undergoing surgery for benign lesions of the
      larynx (n = 10) or the parotid glands (n = 5). All participants answered the DHI
      and VSS-SF and underwent CDP the day before and 3-6 months after surgery. The
      patients with AC also graded their dizziness through the use of a visual analogue
      scale (VAS). RESULTS: Preoperatively, cyst patients scored higher than controls
      on subjective symptoms (DHI, VSS-SF A and VSS-SF V), but not on postural sway
      (CDP). Symptom scores decreased after surgery; the cyst patients improved
      significantly in the subjective tests (DHI, VAS and VSS-SF), while CDP scores did
      not. In the controls, symptom and CDP scores were unchanged after surgery.
      CONCLUSIONS: Patients with temporal AC have a significant preoperative impairment
      and post-operative improvement in their subjective dizziness, but not in postural
      sway as measured by CDP.

PMID- 24117228
TI  - Cellular mechanisms of cadmium-induced toxicity: a review.
AB  - Cadmium is a widespread toxic pollutant of occupational and environmental concern
      because of its diverse toxic effects: extremely protracted biological half-life
      (approximately 20-30 years in humans), low rate of excretion from the body and
      storage predominantly in soft tissues (primarily, liver and kidneys). It is an
      extremely toxic element of continuing concern because environmental levels have
      risen steadily due to continued worldwide anthropogenic mobilization. Cadmium is
      absorbed in significant quantities from cigarette smoke, food, water and air
      contamination and is known to have numerous undesirable effects in both humans
      and animals. Cadmium has a diversity of toxic effects including nephrotoxicity,
      carcinogenicity, teratogenicity and endocrine and reproductive toxicities. At the
      cellular level, cadmium affects cell proliferation, differentiation, apoptosis
      and other cellular activities. Current evidence suggests that exposure to cadmium
      induces genomic instability through complex and multifactorial mechanisms. Most
      important seems to be cadmium interaction with DNA repair mechanism, generation
      of reactive oxygen species and induction of apoptosis. In this article, we have
      reviewed recent developments and findings on cadmium toxicology. 

PMID- 24117229
TI  - Next-generation sequencing of formalin-fixed, paraffin-embedded tumor biopsies:
      navigating the perils of old and new technology to advance cancer diagnosis.

PMID- 24117230
TI  - Adsorption of hydrophobically end-capped poly(ethylene glycol) on cellulose.
AB  - Adsorption of poly(ethylene glycol), hydrophobically end-capped with
      octadecenylsuccinic anhydride (OSA-PEG-OSA), on an ultrathin film of cellulose
      has been studied by quartz crystal microbalance with dissipation monitoring (QCM
      D) and atomic force microscopy (AFM). Normally, PEG does not adsorb on cellulosic
      surfaces, but the use of the telechelic hydrophobic modification was found to
      promote adsorption. The influence of the conformation of the polymer in solution
      prior to adsorption and the subsequent properties of the adsorbed layer were
      investigated. The adsorption experiments were done at concentrations below and
      above the critical association concentration. The adsorption of OSA-PEG-OSA on
      cellulose was observed to occur in four distinct stages. Because of the
      amphiphilic nature of cellulose, further adsorption experiments were performed on
      hydrophobic (polystyrene) and hydrophilic (silica) model substrates to illuminate
      the contribution of hydrophobic and hydrophilic factors in the adsorption
      phenomenon. As expected, the kinetics and the mechanism of adsorption were
      strongly dependent on the chemical composition of the substrate. 

PMID- 24117231
TI  - Modeling of energy transfer from vibrationally excited CO2 molecules: cross
      sections and probabilities for kinetic modeling of atmospheres, flows, and
      plasmas.
AB  - We present extended applications of an established theoretical and computational
      machinery suitable for the study of the dynamics of CO2+CO2 collisions, focusing
      on vibrational energy exchange, considered over a wide range of energies and
      rotational temperatures. Calculations are based on quasi-classical trajectories
      on a potential energy function (a critical component of dynamics simulations),
      tailored to accurately describe the intermolecular interactions, modeled by the
      recently proposed bond-bond semiempirical formulation that allows the colliding
      molecules to be stretchable, rather than frozen at their equilibrium geometry. In
      a previous work, the same potential energy surface has been used to show that
      modifications in the geometry (and in physical properties such as polarizability
      and charge distribution) of the colliding partners affect the intermolecular
      interaction and determine the features of the energy exchange, to a large extent
      driven by long-range forces. As initial partitioning of the energy among the
      molecular degrees of freedom, we consider the excitation of the vibrational
      bending mode, assuming an initial rotational distribution and a rotational
      temperature. The role of the vibrational angular momentum is also carefully
      assessed. Results are obtained by portable implementations of this approach in a
      Grid-computing framework and on high performance platforms. Cross sections are
      basic ingredients to obtain rate constants of use in advanced state-to-state
      kinetic models, under equilibrium or nonequilibrium conditions, and this approach
      is suitable for gas dynamics applications to plasmas and modeling of hypersonic
      flows. 

PMID- 24117232
TI  - Medication adherence in a comparative effectiveness trial for bipolar disorder.
AB  - OBJECTIVE: Psychopharmacology remains the foundation of treatment for bipolar
      disorder, but medication adherence in this population is low (range 20-64%). We
      examined medication adherence in a multisite, comparative effectiveness study of
      lithium. METHOD: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six
      site, randomized effectiveness trial of adjunctive moderate dose lithium therapy
      compared with optimized treatment in adult out-patients with bipolar I or II
      disorder (N=283). Medication adherence was measured at each study visit with the
      Tablet Routine Questionnaire. RESULTS: We found that 4.50% of participants
      reported missing at least 30% of their medications in the past week at baseline
      and non-adherence remained low throughout the trial (<7%). Poor medication
      adherence was associated with more manic symptoms and side-effects as well as
      lower lithium serum levels at mid- and post-treatment, but not with poor quality
      of life, overall severity of illness, or depressive symptoms. CONCLUSION:
      Participants in LiTMUS were highly adherent with taking their medications. The
      lack of association with possible predictors of adherence, such as depression and
      quality of life, could be explained by the limited variance or other factors as
      well as by not using an objective measure of adherence.

PMID- 24117233
TI  - Workplace violence against nurses in emergency departments in Jordan.
AB  - BACKGROUND: Hospital violence against healthcare providers, especially nurses, is
      a significant concern in every healthcare setting in the world. AIM: To assess
      the incidence, characteristics and contributing factors of workplace violence
      committed against nurses in hospital emergency departments in Jordan. METHOD: A
      cross-sectional study design was carried out from 1 May to 31 July 2011. The
      study included the 12 provinces of Jordan by randomly choosing one hospital from
      each province. A convenient sample of 227 nurses met the inclusion criteria. Chi
      square testing and odds ratio were used to analyse the data. FINDINGS: The total
      number of participants was 227. More than three-quarters of the participants
      (75.8%) were exposed to at least one type of violence. The number of incidents of
      verbal violence was approximately fivefold that of the number of incidents of
      physical violence. Among the perpetrators of verbal violence, patients were the
      primary perpetrators. CONCLUSION: Large-scale studies investigating the
      consequences of violence on nursing satisfaction and the quality and quantity of
      care administered to the community in the healthcare sector are recommended.

PMID- 24117235
TI  - Polygraphic findings of 47 cases with respiratory inhibition after crying.
AB  - OBJECTIVE: To report the polygraphic findings of infants with respiratory
      inhibition after crying (RIAC). METHODS: We screened for RIAC among infants with
      a gestational age >=36 weeks using our established method with cranial
      ultrasonography, SpO(2) monitoring and polygraphy. RIAC is defined as central
      apnea that occurred immediately after crying with a decrease in SpO(2) to <60%,
      followed by repeated irregular respiration and apnea as the respiration gradually
      recovered. The subjects were infants with RIAC for whom we could study the
      polygraphic findings in detail. RESULTS: Forty-seven RIAC cases were included in
      the present analysis. The frequency of RIAC was 2.1 (1.2-7.0) times per 24 h. The
      maximum duration of respiratory inhibition was 78.0 (52.6-109.0) s. The maximum
      duration of SpO(2) <60% during RIAC was 39.0 (9.8-93.2) s. The minimum SpO(2)
      value during RIAC was 53.0% (42.2-58.0%). The minimum heart rate during RIAC was
      103.0 (79.1-127.1) bpm. CONCLUSIONS: RIAC is observed among healthy infants, and
      they experience repeated prolonged hypoxemia.

PMID- 24117234
TI  - Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and
      high-dose methotrexate with cytarabine for young patients with high-risk diffuse
      large B-cell lymphoma.
AB  - We conducted a prospective randomized phase II study to evaluate two chemotherapy
      regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine,
      doxorubicin and dexamethasone (R-HCVAD) alternating with rituximab, high-dose
      methotrexate, and cytarabine (R-MA) and (ii) rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone (R-CHOP) in diffuse large B-cell lymphoma
      (DLBCL). This study randomized patients aged <=60 years with DLBCL and an age
      adjusted international prognostic index >=2 to R-HCVAD/R-MA or R-CHOP based on a
      Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients
      showed that the complete response rate (CRR) was higher with R-HCVAD/R-MA than R
      CHOP (P = 0.03); thus, R-CHOP arm was closed. In the final analysis, 49 and 10
      eligible patients were treated in R-HCVAD/R-MA and R-CHOP arms respectively; CRR
      were 82% and 60% respectively (P = 0.13); 3-year progression-free survival (PFS)
      rates were 75.7% and 77.8% respectively (P = 0.53). In the R-HCVAD/R-MA arm, 3
      year PFS rates in patients aged 46-60 years and <=45 years were 70.3% and 87.1%
      respectively (P = 0.13), and the treatment-associated early mortality rate in
      patients >45 years was 12%. In conclusion, R-HCVAD/R-MA is associated with
      excellent outcome in patients <=45 years old. However, in patients >45 years old,
      R-HCVAD/R-MA is associated with unacceptable mortality rates. 

PMID- 24117236
TI  - The Fc receptor-like 3 gene polymorphisms and susceptibility to autoimmune
      diseases: an updated meta-analysis.
AB  - Previous studies have identified several single nucleotide polymorphisms (SNPs)
      of Fc receptor-like 3 (FCRL3), an excellent susceptibility gene, as predisposing
      factors for human autoimmune diseases (ADs). However, the results remain
      inconclusive. To assess the effect of four selected SNPs (rs7528684, rs11264799,
      rs945635 and rs3761959), we conducted a meta-analysis with 34 case-control
      studies. Summary odd ratios (ORs) and 95% confidence intervals (95% CIs) for the
      polymorphisms in FCRL3 and ADs risk were evaluated. Furthermore, this meta
      analysis was performed by using allele comparisons, as well as stratified
      analyses by ethnicity and disease phenotypes under different genetic models. Our
      data showed that the TC, TT + TC genotypes of rs7528684 contributed to a lower
      risk of ADs, compared with the CC carriers (OR = 0.91, 95% CI = 0.85-0.97; OR =
      0.91, 95% CI = 0.85-0.98). In comparison with rs7528684 TC genotype, the TT + CC
      carriers were significantly associated with higher ADs risk (OR = 1.03, 95% CI =
      1.00-1.07). In terms of stratified analyses by ethnicity and disease phenotypes,
      there were significant associations of rs7528684 polymorphism both with ADs in
      Asians and Europeans, and with rheumatoid arthritis, Graves' disease, type-1
      diabetes, and other ADs under different genetic models. Moreover, significant
      associations were also found to be correlated with ADs risk for the SNP
      rs11264799 in mixed subgroup, for rs945635 in Europeans, North Americans and
      mixed group, and for rs3761959 in North Americans. These findings indicate that
      the polymorphisms in FCRL3 may play a role in the pathogenesis of ADs.

PMID- 24117237
TI  - The utility of magnetoencephalography in the presurgical evaluation of refractory
      insular epilepsy.
AB  - PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with
      refractory insular epilepsy. Covered by highly functional temporal, frontal, and
      parietal opercula, insular-onset seizures can manifest a variety of ictal
      symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe
      seizures. Lack of recognition of insular seizures may be responsible for some
      epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG
      data in 14 patients with refractory insular seizures defined through intracranial
      electroencephalography (EEG) or by the presence of an epileptogenic lesion in the
      insula with compatible seizure semiology. MEG was performed as part of the
      noninvasive presurgical evaluation, using a 275-channel whole head MEG system.
      MEG data were analyzed using a single equivalent current dipole model. MEG
      localization was compared to interictal positron emission tomography (PET) and
      ictal single photon emission computed tomography (SPECT) results and to the
      resection margin. KEY FINDINGS: Three patterns of MEG spike sources were
      observed. Seven patients showed an anterior operculoinsular clusters and two
      patients had a posterior operculoinsular cluster. No spikes were detected in one
      patient, and the remaining four patients showed a diffuse perisylvian
      distribution. Spike sources showed uniform orientation perpendicular to the
      sylvian fissure. Nine patients proceeded to insular epilepsy surgery with
      favorable surgical outcome. Among patients with anterior operculoinsular cluster
      who proceeded to have surgery, MEG provided superior information to ictal SPECT
      in four of six patients and to interictal PET in five of six patients.
      SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit
      from epilepsy surgery targeting the insula, particularly if a tight dipole
      cluster is identified even if other noninvasive modalities fail to produce
      localizing results.

PMID- 24117239
TI  - Massachusetts coverage expansion associated with reduction in primary care
      utilization among Medicare beneficiaries.
AB  - OBJECTIVE: To examine whether expanding coverage for the nonelderly affects
      primary care utilization among Medicare beneficiaries. DATA SOURCE: Zip code
      level files from Dartmouth Atlas for Massachusetts and surrounding states,
      including Medicare utilization for 2005 (pre expansion) and 2007 (post
      expansion), and health insurance coverage for 2005. STUDY DESIGN: We use two zip
      code-level outcomes: arc percent change in primary care visits per Medicare
      beneficiary per year, and percentage point change in the share of beneficiaries
      with one or more primary care visits. We use a regression-based difference-in
      difference analysis that compares Massachusetts with surrounding states, and zip
      codes with high, medium, and low uninsurance rates in 2005. The 2005 uninsurance
      rates correspond to the size of Massachusetts' coverage expansion. We use
      propensity scores for identification of comparable zip codes and for weighting.
      PRINCIPAL FINDINGS: In areas of Massachusetts with the highest uninsurance rates
      where insurance expansion had the largest impact-visits per beneficiary fell 6.9
      percent (p < .001) relative to areas of Massachusetts with the smallest
      uninsurance rates. CONCLUSIONS: The expansion of coverage for the nonelderly
      reduced primary care visits, but it did not reduce the percent of beneficiaries
      with at least one visit. These results could imply restricted access, increased
      efficiency, or some blend.

PMID- 24117238
TI  - The regulatory mechanism of a client kinase controlling its own release from
      Hsp90 chaperone machinery through phosphorylation.
AB  - It is believed that the stability and activity of client proteins are passively
      regulated by the Hsp90 (heat-shock protein 90) chaperone machinery, which is
      known to be modulated by its intrinsic ATPase activity, co-chaperones and post
      translational modifications. However, it is unclear whether client proteins
      themselves participate in regulation of the chaperoning process. The present
      study is the first example to show that a client kinase directly regulates Hsp90
      activity, which is a novel level of regulation for the Hsp90 chaperone machinery.
      First, we prove that PKCgamma (protein kinase Cgamma) is a client protein of
      Hsp90alpha, and, that by interacting with PKCgamma, Hsp90alpha prevents PKCgamma
      degradation and facilitates its cytosol-to-membrane translocation and activation.
      A threonine residue set, Thr(115)/Thr(425)/Thr(603), of Hsp90alpha is
      specifically phosphorylated by PKCgamma, and, more interestingly, this threonine
      residue set serves as a 'phosphorylation switch' for Hsp90alpha binding or
      release of PKCgamma. Moreover, phosphorylation of Hsp90alpha by PKCgamma
      decreases the binding affinity of Hsp90alpha towards ATP and co-chaperones such
      as Cdc37 (cell-division cycle 37), thereby decreasing its chaperone activity.
      Further investigation demonstrated that the reciprocal regulation of Hsp90alpha
      and PKCgamma plays a critical role in cancer cells, and that simultaneous
      inhibition of PKCgamma and Hsp90alpha synergistically prevents cell migration and
      promotes apoptosis in cancer cells.

PMID- 24117240
TI  - Bis(2-sulfanylethyl)amido peptides enable native chemical ligation at proline and
      minimize deletion side-product formation.
AB  - Native chemical ligation of C-terminal peptidyl prolyl alkylthioesters with N
      terminal cysteinyl peptides usually exhibits poor kinetic rates compared to other
      C-terminal amino acid residues. It is shown here that the reaction is accompanied
      by the formation of a deletion side product which is minimized by using a bis(2
      sulfanylethyl)amido (SEA) thioester surrogate at a mildly acidic pH. 

PMID- 24117241
TI  - Muscle strength in myasthenia gravis.
AB  - OBJECTIVE: Myasthenia gravis (MG) is characterized by fatigue and fluctuating
      muscle weakness as a result of impaired neuromuscular transmission (NMT).
      Although MG is a prototypic fatiguing disorder, little is known about how the
      condition affects fixed weakness, and if present, whether weakness is related to
      disease duration or gender. The aim of this study was to quantify the strength of
      patients with MG and investigate whether it is related to disease duration.
      METHODS: Eight muscle groups were tested by manual muscle testing and with a hand
      held dynamometer in 38 patients with generalized MG and 37 healthy age- and
      gender-matched controls. The disease duration was recorded and compared with
      strength measures. RESULTS: On average, muscle strength was decreased by 28%
      compared with controls (P<0.01). Repeated strength measures in individual
      patients did not differ, suggesting that the muscle force reported was not
      subject to fatigue, but reflected fixed weakness. The male patients showed a
      greater reduction in muscle force in all eight muscle groups than women with MG
      (60% vs 77% of normal, P<0.05). In both men and women with MG, strength in
      shoulder abductors was most affected (51% vs 62% of normal). Muscle strength and
      disease duration were not related. CONCLUSIONS: These findings show that patients
      with generalized MG have (i) a significant generalized, fixed muscle weakness,
      (ii) that male patients with MG have a more severe muscle weakness than women,
      (iii) that proximal upper limb muscles are most affected, and (iv) that disease
      duration alone is not a predictor of loss of muscle strength.

PMID- 24117242
TI  - Measuring intermittent exercise performance using shuttle running.
AB  - The aim of this study was to include self-paced exercise within a modified
      Loughborough Intermittent Shuttle Test (LIST-P) in order to quantify key
      performance variables not possible with prescribed workloads. Sixteen male games
      players performed two trials of the LIST-P, at least 7 days apart. The LIST-P
      incorporates 4 * 15-min blocks of "prescribed-pace" activity (participants
      exercise in time to audible signals) followed by 2 * 15-min blocks of "self
      paced" running (no audible signals). Distances covered and mean speeds were
      monitored during self-paced exercise. Total distance covered (12.54 +/- 0.45 km
      vs. 12.64 +/- 0.32 km; P = 0.10) and mean speed (8.37 +/- 0.31 km ? h(-1) vs.
      8.44 +/- 0.22 km ? h(-1); P = 0.10) was similar between trials. Other indices
      also showed the test to be reliable (Pearson's correlation = 0.89 and 0.90 (P <
      0.01), total distance and mean speed, respectively; intraclass correlation
      coefficient = 0.88 and 0.88 (P < 0.01); standard error of measurement = +/-0.13
      km and +/-0.09 km ? h(-1); coefficient of variation (CV) = 1.7% and 1.7%; ratio
      limits of agreement = 1.00 *//1.03 and 1.01 *//1.04). Sprint time was also
      similar between trials (2.60 +/- 0.19 s vs. 2.64 +/- 0.23 s; P = 0.29).
      Incorporating self-paced exercise within an established intermittent shuttle
      running test appears to be a sensitive means of quantifying key performance
      variables for multiple-sprint sports research.

PMID- 24117243
TI  - Reading the British Journal of Dermatology.

PMID- 24117244
TI  - A TREAT in store for those wishing to identify uncertainties in the treatment of
      severe childhood eczema.

PMID- 24117245
TI  - Nickel allergy following EU regulation--more action is needed.

PMID- 24117248
TI  - Conjugating S-nitrosothiols with glutathiose stabilized silver sulfide quantum
      dots for controlled nitric oxide release and near-infrared fluorescence imaging.
AB  - Light-controllable nitric oxide (NO) delivery nanoparticles with the capability
      of near-infrared (NIR) fluorescence imaging were reported. Water-dispersible Ag2S
      quantum dots (QDs) were synthesized via a one-pot procedure using reduced
      glutathiose (GSH) as both sulfur source and stabilizer. S-nitrosothiols (RSNOs)
      were conjugated with the GSH stabilized Ag2S QDs at the amino groups of the GSH,
      leading to Ag2S-GSH-SNO nanoparticles with dimension of ~5.5 nm. The
      biocompatible Ag2S-GSH-SNO nanoparticles could release NO under UV or visible
      irradiation and emit NIR fluorescence under NIR excitation for bioimaging at
      physiological pH and temperature, yet could hardly release NO when NIR
      irradiation was applied. In vitro cell imaging and mice imaging experiments
      demonstrated that the Ag2S-GSH-SNO nanoparticles could emit readily observable
      NIR fluorescence and release NO in living cells and small animals. The NIR
      fluorescence imaging of the Ag2S-GSH-SNO nanoparticles would not interfere with
      the light-triggered NO release from them, as the excitation lights needed for
      these two functions were in different wavelength regions. This work provides new
      perspectives for the application of multifunctional nanostructured materials in
      diagnostics and imaging.

PMID- 24117249
TI  - Building an open academic environment - a new approach to empowering students in
      their learning of anatomy through 'Shadow Modules'.
AB  - Teaching and learning in anatomy is undertaken by a variety of methodologies, yet
      all of these pedagogies benefit from students discussing and reflecting upon
      their learning activities. An approach of particular potency is peer-mediated
      learning, through either peer-teaching or collaborative peer-learning.
      Collaborative, peer-mediated, learning activities help promote deep learning
      approaches and foster communities of practice in learning. Students generally
      flourish in collaborative learning settings but there are limitations to the
      benefits of collaborative learning undertaken solely within the confines of
      modular curricula. We describe the development of peer-mediated learning through
      student-focused and student-led study groups we have termed 'Shadow Modules'. The
      'Shadow Module' takes place parallel to the formal academically taught module and
      facilitates collaboration between students to support their learning for that
      module. In 'Shadow Module' activities, students collaborate towards curating
      existing online open resources as well as developing learning resources of their
      own to support their study. Through the use of communication technologies and Web
      2.0 tools these resources are able to be shared with their peers, thus enhancing
      the learning experience of all students following the module. The Shadow Module
      activities have the potential to lead to participants feeling a greater sense of
      engagement with the subject material, as well as improving their study and group
      working skills and developing digital literacy. The outputs from Shadow Module
      collaborative work are open-source and may be utilised by subsequent student
      cohorts, thus building up a repository of learning resources designed by and for
      students. Shadow Module activities would benefit all pedagogies in the study of
      anatomy, and support students moving from being passive consumers to active
      participants in learning. 

PMID- 24117250
TI  - Androgen activity, ischaemic heart disease and risk factors among men in NHANES
      III.
AB  - AIM: Observationally, low serum testosterone among men is associated with
      cardiovascular diseases and its risk factors, but it is unclear whether raising
      endogenous androgens would be protective. To clarify the role of androgens, the
      association of two different androgen biomarkers (serum testosterone and
      androstanediol glucuronide) with cardiovascular disease risk factors and
      mortality was examined in a nationally representative sample of US men. RESEARCH
      DESIGN AND METHODS: Multivariable linear and proportion hazards regression were
      used to examine the adjusted associations of serum testosterone and
      androstanediol glucuronide with cardiovascular disease risk factors and death
      from major cardiovascular diseases in 1460 men from NHANES III phase 1 (1988
      1991) followed-up through 2006. RESULTS: Serum testosterone and androstanediol
      glucuronide were weakly correlated (0.13). Serum testosterone was associated with
      healthier values of most cardiovascular disease risk factors but not with death
      from ischaemic heart disease or stroke, adjusted for age, education,
      race/ethnicity, smoking and alcohol use. Similarly adjusted, androstanediol
      glucuronide was associated with unhealthier values of some cardiovascular risk
      factors and death from ischaemic heart disease (hazard ratio 1.16, 95% confidence
      interval 1.003-1.33 per standard deviation). CONCLUSIONS: Androgen biomarkers had
      inconsistent associations with cardiovascular disease risk factors and ischaemic
      heart disease. Androstanediol glucuronide, rather than serum testosterone, had
      associations with cardiovascular disease risk factors more similar to those seen
      in randomized controlled trials of testosterone therapy, with corresponding
      implications for raising androgens.

PMID- 24117251
TI  - Diazonium cation-exchanged clay: an efficient, unfrequented route for making
      clay/polymer nanocomposites.
AB  - We describe a simple, off-the-beaten-path strategy for making clay/polymer
      nanocomposites through tandem diazonium salt interface chemistry and radical
      photopolymerization. Prior to photopolymerization, sodium montmorillonite (MMT)
      was ion exchanged with N,N'-dimethylbenzenediazonium cation (DMA) from the
      tetrafluoroborate salt precursor. DMA acts as a hydrogen donor for benzophenone
      in solution; this pair of co-initiators permits us to photopolymerize glycidyl
      methacrylate (GMA) between the lamellae of the diazonium-modified clay, therefore
      providing intercalated MMT-PGMA nanocomposites with an onset of exfoliation. This
      work conclusively provides a new approach for bridging reactive and functional
      polymers to layered nanomaterials via aryl diazonium salts in a simple, fast,
      efficient cation-exchange approach. 

PMID- 24117252
TI  - Riluzole activates TRPC5 channels independently of PLC activity.
AB  - BACKGROUND AND PURPOSE: The transient receptor potential channel C5 (TRPC5) is a
      Ca(2+)-permeable cation channel, which is predominantly expressed in the brain.
      TRPC5 is activated in a PLC-dependent manner by, as yet, unidentified endogenous
      messengers. Recently, modulators of TRPC5, like Ca(2+), pH and phospholipids,
      have been identified. However, the role of TRPC5 in vivo is only poorly
      understood. Novel specific modulators of TRPC5 might help to elucidate its
      function. EXPERIMENTAL APPROACH: Novel modulators of TRPC5 were identified in a
      compound screening of approved drugs and natural compounds. The potency and
      selectivity of TRPC5-activating compounds were determined by fluorometric calcium
      imaging. The biophysical properties of channel activation by these compounds were
      analysed using electrophysiological measurements. KEY RESULTS: Riluzole was
      identified as a novel activator of TRPC5 (EC50 9.2 +/- 0.5 MUM) and its mechanism
      of action was shown to be independent of G protein signalling and PLC activity.
      Riluzole-induced TRPC5 currents were potentiated by La(3+) and, utilizing TRPC5
      mutants that lack La(3+) binding sites, it was confirmed that riluzole and La(3+)
      activate TRPC5 by different mechanisms. Recordings of excised inside-out patches
      revealed a relatively direct effect of riluzole on TRPC5. CONCLUSIONS AND
      IMPLICATIONS: Riluzole can activate TRPC5 heterologously expressed in HEK293
      cells as well as those endogenously expressed in the U-87 glioblastoma cell line.
      Riluzole does not activate any other member of the TRPC family and could,
      therefore, despite its action on other ion channels, be a useful pharmacological
      tool for identifying TRPC5-specific currents in immortalized cell lines or in
      acutely isolated primary cells.

PMID- 24117254
TI  - Leptin-activity blockers: development and potential use in experimental biology
      and medicine.
AB  - The first adipokine, leptin, discovered almost 20 years ago, is secreted into
      circulation mainly from adipose tissue and acts both centrally and peripherally.
      Leptin regulates energy metabolism, reproductive function, bone metabolism, and
      immune response. However in some physiological or pathological situations such as
      enhancement of undesired immune responses in autoimmune diseases, tumorigenesis,
      elevated blood pressure, and certain cardiovascular pathologies, leptin activity
      may be harmful. In this review we screen different approaches to blocking leptin
      action, in vitro and in vivo. The recent development of superactive leptin
      muteins exhibiting antagonistic properties, and other leptin-action-blocking
      peptides, proteins, monoclonal antibodies, and nanobodies, opens new perspectives
      for their use in research, and eventually, therapy for cachexia, autoimmune
      disease, cancer, and other pathologies. 

PMID- 24117253
TI  - Metabolic inflammation: role of cytokines in the crosstalk between adipose tissue
      and liver.
AB  - The innate immune system and its major mediators, i.e., cytokines, are
      increasingly recognized as being of crucial importance in metabolic inflammation
      as observed in morbid obesity and type 2 diabetes (T2D). Morbid obesity is
      commonly associated with adipose tissue inflammation. Adipose tissue inflammation
      is characterized by an increased expression of various pro-inflammatory cytokines
      such as tumor necrosis factor-alpha, interleukin-1 and -6, and by a rather
      heterogenous cellular infiltrate including monocytes/macrophages, neutrophils, B
      lymphocytes, T lymphocytes, and others. It has been demonstrated that in patients
      with severe obesity and fatty liver disease, expression of these pro-inflammatory
      cytokines in adipose tissue is 100-1000 times higher compared with that in the
      liver. Therefore, the adipose tissue can be considered in the state of severe
      obesity as the "cytokine factory" of the body. Rapid weight loss almost entirely
      eliminates pro-inflammatory cytokines in the adipose tissue, and therefore
      provides a very potent anti-inflammatory strategy. In conclusion, there is
      increasing evidence that peripheral tissues such as the adipose tissue may affect
      disease processes in target organs such as the liver, pancreas, heart, or blood
      vessels, and may therefore significantly contribute to chronic inflammation as
      observed in obesity and T2D. 

PMID- 24117255
TI  - The potential contribution of circulating and locally produced leptin to cardiac
      hypertrophy and failure.
AB  - Leptin is a 16 kDa peptide that was first identified in 1994 through positional
      cloning of the mouse obesity gene. Although the primary function of leptin is to
      act a satiety factor through its actions on the hypothalamus, it is now widely
      recognized that leptin can exert effects on many other organs through activation
      of its receptors, which are ubiquitously expressed. Leptin is secreted primarily
      by white adipocytes, but it is also produced by other tissues including the heart
      where it can exert effects in an autocrine or paracrine manner. One of these
      effects involves the induction of cardiomyocyte hypertrophy, which appears to
      occur via multiple cell signalling mechanisms. As adipocytes are the primary site
      of leptin production, plasma leptin concentrations are generally positively
      related with body mass index and the degree of adiposity. However,
      hyperleptinemia is also associated with cardiovascular disease, including heart
      failure, in the absence of obesity. Here we review the potential role of leptin
      in heart disease, particularly pertaining to its potential contribution to
      myocardial remodelling and heart failure, as well as the underlying mechanisms.
      We further discuss potential interactions between leptin and another adipokine,
      adiponectin, and the potential implications of this interaction in terms of fully
      understanding leptin's effects. 

PMID- 24117256
TI  - Endogenous hydrogen sulfide in perivascular adipose tissue: role in the
      regulation of vascular tone in physiology and pathology.
AB  - Hydrogen sulfide (H2S) is synthesized from L-cysteine by cystathionine beta
      synthase (CBS) or cystathionine gamma-lyase (CSE), and is enzymatically
      metabolized in mitochondria by sulfide:quinone oxidoreductase (SQR). Recent
      studies have indicated that H2S is synthesized by CSE in perivascular adipose
      tissue (PVAT), and is responsible for the anticontractile effect of PVAT on
      adjacent vessels. The lipophilic statin atorvastatin increases PVAT-derived H2S
      by suppressing its mitochondrial oxidation; the effect that results from statin
      induced depletion of ubiquinone. Experimental obesity induced by a highly
      palatable diet has a time-dependent effect on H2S in PVAT. Adipose tissue hypoxia
      suppresses H2S oxidation and increases its level in short-term obesity not
      associated with insulin resistance. In contrast, in long-term obesity, insulin
      resistance and (or) hyperinsulinemia result in the down-regulation of CSE and H2S
      deficiency, which is corrected by treatment with the insulin sensitizer
      rosiglitazone. In addition, cannabinoid CB1 receptor agonist administered for 2
      weeks increases H2S by impairing mitochondria biogenesis. This indicates that the
      rate of mitochondrial H2S oxidation plays an important role in the regulation of
      H2S level in PVAT. Up-regulation of H2S signaling in short-term obesity and (or)
      by elevated endocannabinoids may be a compensatory mechanism that maintains
      vascular tone, despite endothelial dysfunction.

PMID- 24117257
TI  - Kalpaamruthaa modulates oxidative stress in cardiovascular complication
      associated with type 2 diabetes mellitus through PKC-beta/Akt signaling.
AB  - This study aimed at investigating the efficacy of Kalpaamruthaa (KA) on
      cardiovascular damage (CVD) associated with type 2 diabetes mellitus in
      experimental rats by reducing oxidative stress and the modulation of the protein
      kinase C-beta (PKC-beta)/Akt signaling pathway. CVD-induced rats were treated
      with KA (200 mg.(kg body mass)(-1).(day)(-1)) orally for 4 weeks. KA effectively
      reduced insulin resistance with alterations in blood glucose, hemoglobin, and
      glycosylated hemoglobin in CVD-induced rats. Elevated levels of lipids in CVD
      induced rats were decreased upon KA administration. In CVD-induced rats the
      levels of lipoproteins were returned to normal by KA treatment. KA effectively
      reduced the lipid peroxidative product and protein carbonyl content in liver of
      CVD-induced rats. KA increased the activities and (or) levels of enzymatic and
      nonenzymatic antioxidants in liver of CVD-induced rats. KA treatment reduced the
      fatty inclusion and mast cell infiltration in liver of CVD-induced rats. Further,
      treatment with KA reduced the chromatin condensation and marginization in
      myocardium of CVD-induced rats. KA alters insulin signaling by decreasing PKC
      beta and increasing p-Akt and GLUT4 expressions in heart of CVD-induced rats. The
      above findings suggest that KA renders protection against CVD induced by type 2
      diabetes mellitus by augmenting the cellular antioxidant defense capacity and
      modulating PKC-beta and the p-Akt signaling pathway. 

PMID- 24117258
TI  - High-fat diet stimulates hepatic cystathionine beta-synthase and cystathionine
      gamma-lyase expression.
AB  - Cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) catalyze
      homocysteine (Hcy) metabolism via the trans-sulfuration pathway. They are also
      responsible for hydrogen sulfide (H2S) production via desulfuration reactions.
      The liver contributes significantly to the regulation of Hcy and H2S homeostasis,
      which might participate in many physiological and pathological processes. The aim
      of this study was to investigate the effect of a high-fat diet (HFD) on hepatic
      CBS and CSE expression and its impact on Hcy and H2S metabolism. Mice (C57BL/6)
      fed a HFD (60% kcal fat) for 5 weeks developed fatty liver. The mRNA and protein
      levels of CBS and CSE in the liver were significantly elevated in mice fed a HFD.
      Subsequently the metabolism of Hcy by CBS and CSE was increased in the liver, and
      its level decreased in the circulation. Increased CBS and CSE expression also
      caused a significant elevation in H2S production in the liver. The level of lipid
      peroxides was elevated, indicating oxidative stress, while the level of total
      glutathione remained unchanged in the liver of HFD-fed mice. Upregulation of the
      trans-sulfuration pathway might play an adaptive role against oxidative stress by
      maintaining total glutathione levels in the liver. 

PMID- 24117259
TI  - Pre- or post-treatment with aminoguanidine attenuates a renal distal
      acidification defect induced by acute ureteral obstruction in rats.
AB  - Acute unilateral ureteral obstruction (UUO) impairs distal nephron acid secretion
      and stimulates expression of inducible nitric oxide synthase (iNOS) in post
      obstructed kidney (POK). This study investigated the influence of pre- or post
      treatment with aminoguanidine as a selective iNOS inhibitor on UUO-induced renal
      functional disturbances. To induce acute UUO, the left ureter in rats was ligated
      and released after 24 h. Then, a 3 h clearance period followed by bicarbonate
      loading and thereafter a 30 min clearance period were allocated. Aminoguanidine
      was administered either prior to the UUO induction or after release of the
      obstruction in the different rat groups, while untreated and sham groups received
      normal saline. During the first clearance period, fractional bicarbonate
      excretion and urinary pH increased markedly in the POK of the untreated group
      compared with the left kidney of sham group, and a large drop in the difference
      between urine and blood pCO2 (U-B pCO2) was observed after bicarbonate loading;
      all of these parameters were ameliorated in the pre-treated and post-treated
      groups. However, the UUO-induced decreases in creatinine clearance, sodium
      reabsorption, urine osmolality, and free-water reabsorption in the POK were
      attenuated only in the post-treated group. Therefore, the in vivo application of
      a selective iNOS inhibitor partially improved the acute UUO-induced distal
      nephron acidification defect, while post-treatment but not pre-treatment with
      aminoguanidine ameliorated decrements of glomerular filtration, sodium
      reabsorption, and urine-concentrating ability. 

PMID- 24117260
TI  - In-vitro analysis of rhBMP-2 effects in human osteogenic cells.
AB  - This study evaluated the in vitro expression of bone-related proteins by
      osteoblasts in the presence of different concentrations of human recombinant bone
      morphogenetic protein-2 (rhBMP-2). Immortalized human fetal osteoblastic cell
      line 1.19 (hFOB) were exposed to different concentrations of rhBMP-2 (10, 50, or
      100 ng/mL) for 72 h. Cell proliferation and viability (MTT assay), as well as the
      expression of fibronectin, osteonectin, and osteopontin were assessed by indirect
      immunofluorescence and Western blot. Neither of the 3 concentrations of rhBMP-2
      caused statistically significant alterations in cell proliferation and viability,
      although the concentration of 100 ng/mL showed lower values for both assays after
      both 48 and 72 h of exposure. There was no alteration in the expression of
      noncollagenous proteins, as analyzed by immunofluorescence, when compared with
      the control group. Furthermore, in the Western blot assay we observed a
      statistically significant decrease in fibronectin and osteonectin at 100 ng rhBMP
      2/mL (p < 0.05) by comparison with the medium alone. The expression of
      osteopontin decreased slightly in all 3 concentrations of rhBMP-2 tested;
      however, the change was not statistically significant (p > 0.05). In this in
      vitro study, the tested concentrations of rhBMP-2 appeared to decrease the
      expression of important bone-related molecules in pre-osteoblast cells. 

PMID- 24117261
TI  - Co-administration of aqueous ginseng extract with tobramycin stimulates the pro
      inflammatory response and promotes the killing of Pseudomonas aeruginosa in the
      lungs of infected rats.
AB  - North American ginseng is known to have immunomodulatory and antipseudomonal
      properties in vitro. In this study we investigated the effects of aqueous ginseng
      extract, either alone or in a combination with the antibiotic tobramycin, in an
      animal model of chronic Pseudomonas aeruginosa lung infection. The lungs of male
      rats (n = 5) were infected with P. aeruginosa (2 * 10(8) cfu/mL) in agar-beads by
      intratracheal instillation. Starting on day 7 post-infection, animals were
      treated daily for 3 consecutive days with saline, tobramycin (300 MUg/kg body
      mass, intratracheal), and (or) ginseng (100 mg/kg body mass, subcutaneous);
      animals were sacrificed 24 h after the third drug treatment. Lung bacteria
      counts, cytokine levels in sera, and lung histopathology were examined. The
      treatment of infected animals with tobramycin [6.6 * 10(4) colony forming units
      (cfu)], ginseng (5.3 * 10(4) cfu), or tobramycin plus ginseng (2.0 * 10(3) cfu)
      lessened the lung infection compared with the control group (saline treated) (6.0
      * 10(6) cfu). The levels of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL
      12p70, IFN-gamma, GM-CSF, TNF-alpha) in infected animals were significantly
      increased with co-treatment of ginseng plus tobramycin. These data suggest that
      co-administration of aqueous ginseng extract and tobramycin stimulated the pro
      inflammatory response and promoted the killing of P. aeruginosa. 

PMID- 24117262
TI  - Effects of tumor necrosis factor alpha on leptin-sensitive intestinal vagal
      mechanoreceptors in the cat.
AB  - The involvement of tumour necrosis factor alpha (TNF-alpha) in inflammatory bowel
      disease (IBD) has been established, and anti-TNF-alpha has been suggested as a
      therapeutic approach for the treatment of these pathologies. We studied the
      effects of TNF-alpha on leptin-sensitive intestinal vagal units to determine
      whether TNF-alpha exerts its effects through the intestinal vagal
      mechanoreceptors and to investigate its interactions with substances regulating
      food intake. The activity of intestinal vagal mechanoreceptors was recorded via
      microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF
      alpha (1 MUg, i.a.) increased the discharge frequency of leptin-activated units
      (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin
      inhibited units (type 2 units). When TNF-alpha was administered 20 min after
      sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were
      significantly enhanced (P < 0.0001) and type 2 units were significantly (P <
      0.05) activated. Pre-treatment with Il-1ra (250 MUg, i.a.) blocked the excitatory
      effects of TNF-alpha on type 1 units whereas the excitatory effects of TNF-alpha
      administration after CCK treatment on type 2 units were not modified. The
      activation of leptin-sensitive units by TNF-alpha may explain, at least in part,
      the weight loss observed in IBD. 

PMID- 24117263
TI  - Quercetin provides greater cardioprotective effect than its glycoside derivative
      rutin on isoproterenol-induced cardiac fibrosis in the rat.
AB  - Quercetin exhibits numerous pharmacological effects, including the capacity for
      cardioprotection. This study aimed to investigate whether quercetin or its
      glycoside derivative rutin has any protective action against isoproterenol (ISO)
      induced cardiac fibrosis, and investigate the structure-activity relationship.
      Male Wistar rats were injected subcutaneously with ISO (15 mg.(kg body mass)(-1))
      to induce experimental cardiac fibrosis. The cardioprotective effect of co
      treatment with quercetin (25 or 50 mg.kg(-1)) or rutin (25 or 50 mg.kg(-1)) was
      investigated in ISO-induced cardiac fibrosis in rats. The administration of
      quercetin and rutin signifcantly decreased the cardiac weight index and
      myocardial enzyme activity, increased the activity of superoxide dismutase in the
      serum, and inhibited the ISO-induced increase in angiotensin II and aldosterone
      in the plasma. Furthermore, overexpression of transforming growth factor beta1
      (TGF-beta1), connective tissue growth factor (CTGF), and excessive deposition of
      extracellular matrix (ECM) in isoproterenol-treated myocardial tissues were
      normalized by quercetin and rutin. Our results suggest that both quercetin and
      rutin exhibited cardioprotective effects in cardiac fibrosis induced by ISO in
      the rat heart. Moreover, the effects of rutin are weaker than quercetin at the
      same dose. The mechanism of these effects may be related to antioxidative stress,
      inhibition of the renin-angiotensin-aldosterone system, decrease in the
      expression of TGF-beta1 and CTGF, and the subsequent reduction in the deposition
      of the ECM. 

PMID- 24117264
TI  - The effects of fish oil consumption on cardiovascular remodeling in ApoE
      deficient mice.
AB  - Owing to their spontaneous development of atherosclerosis, apolipoprotein E
      knockout mice (ApoE(KO)) are one of the best studied animal models for this
      disease. Little is known about the utility of various omega-3 fatty acid
      regimens, in particular fish oils, in preventing cardiac disease in ApoE(KO)
      mice. The purpose of this study was to determine the cardiovascular effects of
      omega-3 fatty acid supplementation with either safflower oil (control), fish oil,
      flaxseed oil, or designed oil in ApoE(KO) mice fed a high-fat diet for a total of
      16 weeks. In-vivo cardiac function was assessed weekly using murine
      echocardiography. Blood pressure, plasma lipid levels, and brain natriuretic
      peptide (BNP) were serially measured. The results show that ApoE(KO) mice fed
      fish oil demonstrated an increase in left ventricular wall thickness as a result
      of increased afterload. Despite chronic treatment with fish oil over 16 weeks,
      blood pressure increased in ApoE(KO) mice by 20% compared with the baseline. Both
      echocardiographic evidence of left ventricular hypertrophy and biochemical
      increase in BNP levels confirmed diastolic dysfunction in ApoE(KO) mice fed fish
      oil. This suggests that high-fat diet supplemented with fish oil may lead to
      adverse cardiovascular effects in ApoE deficient mice. 

PMID- 24117265
TI  - Parvalbumin is overexpressed in the late phase of pharmacological preconditioning
      in skeletal muscle.
AB  - Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K(+)
      channel openers such as diazoxide, provides protection against ischemia in
      cardiac muscle, skeletal muscle, and other tissues. Effects on Ca(2+) homeostasis
      during the late phase of PPC have been described in cardiomyocytes, but no
      information is available regarding intracellular Ca(2+) changes in skeletal
      muscle fibers during late PPC. Intracellular Ca(2+) signals were measured in
      single fibers of adult mouse skeletal muscle, with fluorescent probes, 48 h after
      the administration of diazoxide. Parvalbumin levels in the myofibers were
      quantitated by Western blot. Diazoxide induction of late PPC was confirmed by
      partial protection of muscles from peroxide-induced damage. Late PPC was
      associated with a significant decrease in the duration of Ca(2+) signals during
      single twitches and tetanus with no changes in peak values. This effect was
      prevented by the reactive oxygen species (ROS) scavenger tiron. Late PPC was
      accompanied by a 30% increase in parvalbumin levels, and this effect was also
      blocked by tiron. Our data show, for the first time, a role of parvalbumin in
      late PPC in skeletal muscle. 

PMID- 24117266
TI  - Proteomic study on the protective mechanism of fibroblast growth factor 21 to
      ischemia-reperfusion injury.
AB  - Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent
      glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering
      effects in rodent models of diabetes. In this study, we found that FGF-21 can
      significantly attenuate ischemia-reperfusion (I/R) induced damage in H9c2 cells
      (rat heart). However, it is unclear which signal transduction pathway is involved
      in the cardioprotective effect of FGF-21. Thus, this study was designed to
      investigate the potential mechanism induced by FGF-21. The results showed that
      FGF-21 treatment prevented the oxidative stress and apoptosis associated with I/R
      damage by reducing the levels of superoxide anions, inhibiting glycogen synthase
      kinase (GSK) 3beta by activating Akt phosphorylation, and recovering the levels
      of ATP synthase pyruvate kinase isozymes M1 and protein kinase C, thereby
      improving energy supply. In summary, we conclude that FGF-21 protects H9c2 cells
      against I/R injury mainly through the Akt-GSK-3beta-caspase-3 dependent pathway,
      preventing oxidative stress, and recovery of the energy supply. 

PMID- 24117267
TI  - On being scientifically different.

PMID- 24117269
TI  - A primer on the treatment of schizophrenia through repetitive transcranial
      magnetic stimulation.

PMID- 24117268
TI  - Role of CXCR2 and TRPV1 in functional, inflammatory and behavioural changes in
      the rat model of cyclophosphamide-induced haemorrhagic cystitis.
AB  - BACKGROUND AND PURPOSE: Cyclophosphamide induces urotoxicity characterized by the
      development of cystitis, which involves bladder overactivity and inflammation.
      Here, we investigated the roles of chemokine receptor 2 (CXCR2) and transient
      receptor potential vanilloid 1 (TRPV1) channels in a rat model of
      cyclophosphamide-induced cystitis. EXPERIMENTAL APPROACH: Cystitis induced by
      cyclophosphamide in rats was assessed by gross morphology, histology and
      immunohistochemistry of bladder tissue. mRNA for CXCR2 and TRPV1 channels were
      measured by RT-PCR. Nociceptive responses in paw and abdomen, along with
      cystometric measures were recorded. KEY RESULTS: Cyclophosphamide, i.p., induced
      pain behaviour, bladder inflammation and voiding dysfunction. The CXCR2
      antagonist, SB225002, the TRPV1 channel antagonist, SB366791 or their combination
      reduced the mechanical hypersensitivity of paw and abdominal area and nociceptive
      behaviour after cyclophosphamide. Cyclophosphamide-induced cystitis was
      characterized by haemorrhage, oedema, neutrophil infiltration and other
      inflammatory changes, which were markedly decreased by the antagonists. Up
      regulation of CXCR2 and TRPV1 mRNA in the bladder after cyclophosphamide was
      inhibited by SB225002, SB366791 or their combination. Expression of CXCR2 and
      TRPV1 channels was increased in the urothelium after cyclophosphamide. Bladder
      dysfunction was shown by increased number of non-voiding contractions (NVCs) and
      bladder pressures and a reduction in bladder capacity (BC), voided volume (VV)
      and voiding efficiency (VE). SB225002 or its combination with SB366791 reduced
      bladder pressures, whereas SB225002, SB366791 or their combination increased BC,
      VV and VE, and also reduced the number of NVCs. CONCLUSIONS AND IMPLICATIONS:
      CXCR2 and TRPV1 channels play important roles in cyclophosphamide-induced
      cystitis in rats and could provide potential therapeutic targets for cystitis.

PMID- 24117272
TI  - Elderly patients with glioblastoma: the treatment challenge.
AB  - The treatment for elderly patients affected by glioblastoma represents a
      challenge in neuro-oncology. The recent randomized trials (the NOA-8 and the
      NCBTSG trials) showed an advantage of temozolomide for patients with O6
      methylguanine methyltransferase methylated tumors. To date, no randomized trials
      compared the standard treatment (radiochemotherapy) with other therapeutic
      approaches, due to the idea that elderly patients do not tolerate aggressive
      therapy. Nonetheless, with the increased lifespan and the better quality of life,
      the nihilism in the treatment of elderly with cancer is obsolete. Molecular
      (including O6-methylguanine methyltransferase) and clinical tools (including the
      geriatric evaluation) are needed for choosing the proper therapy for patients
      over 70. 

PMID- 24117273
TI  - The circadian rhythm in adult attention-deficit/hyperactivity disorder: current
      state of affairs.
AB  - Adults with ADHD often have sleep problems that are caused by a delay of their
      internal circadian rhythm system. Such individuals are often typified as
      'evening' or 'night' persons. This review focuses on the link between ADHD
      symptoms and the evening typology through multiple pathways. Etiology of the
      internal circadian rhythm system, the genetic basis for evening typology, overlap
      between ADHD symptoms and evening preference and risk factors for various chronic
      health conditions, including metabolic syndrome and cancer, are discussed. The
      treatment perspectives to reset the delayed rhythm in adults with ADHD involve
      psychoeducation on sleep hygiene, melatonin in the afternoon or evening and
      bright light therapy in the morning. 

PMID- 24117271
TI  - Ependymomas: development of immunotherapeutic strategies.
AB  - Ependymomas are among the most challenging childhood brain tumors. Although 50
      70% of ependymomas are cured with surgery and irradiation, a significant
      percentage of tumors recur. Ependymomas that are not amenable to complete
      resection at diagnosis have a particularly poor prognosis, and the vast majority
      of affected children experience tumor recurrence. Although transient responses
      have been observed in recurrent tumors treated with re-irradiation and several
      chemotherapy regimens, long-term disease control is rarely achieved. Children
      with recurrent disease commonly experience cumulative neurological morbidity from
      repeated surgical and adjuvant therapy interventions and almost universally
      succumb to refractory tumor progression. Accordingly, conceptually new treatment
      approaches are needed, both to decrease the risk of tumor recurrence and to
      enhance disease control in those children who experience recurrent disease. This
      article reviews the current application of risk-based treatment stratification at
      diagnosis, the rationale for exploring the role of novel therapeutic strategies
      such as immunotherapy at recurrence and the concept behind a vaccine-based trial
      for these tumors. 

PMID- 24117274
TI  - The comorbidity of ADHD and autism spectrum disorder.
AB  - ADHD and autism spectrum disorder are common psychiatric comorbidities to each
      another. In addition, there is behavioral, biological and neuropsychological
      overlap between the two disorders. There are also several important differences
      between autism spectrum disorder and ADHD. Treatment strategies for the comorbid
      condition will also be reviewed. Future areas of research and clinical need will
      be discussed. 

PMID- 24117275
TI  - Sleep apnea headache: a growing concern in an increasingly obese population?
AB  - Sleep apnea headache is a recurrent universal pressing headache without
      accompanying symptoms at awakening that resolves within 4 h. The diagnosis
      requires polysomnography-verified apnea hypopnea index>=5, that is, obstructive
      sleep apnea (OSA). Morning headache has similar symptomatology without OSA. The
      prevalence of sleep apnea headache is 10-15% in people with OSA, whereas morning
      headache occurs in 5%. The severity of OSA only slightly affects the prevalence
      of sleep apnea headache. The pathophysiology of sleep apnea headache remains an
      enigma, since average oxygen desaturation and lowest oxygen saturation are
      similar in OSA people without sleep apnea headache. Migraine and tension-type
      headache are unrelated to OSA. Thus, growing concern of sleep apnea headache in
      an increasingly obese population is unfounded with our current knowledge.

PMID- 24117276
TI  - Free energy barrier for melittin reorientation from a membrane-bound state to a
      transmembrane state.
AB  - An important step in a phospholipid membrane pore formation by melittin
      antimicrobial peptide is a reorientation of the peptide from a surface into a
      transmembrane conformation. Experiments measure the fraction of peptides in the
      surface state and the transmembrane state, but no computational study exists that
      quantifies the free energy curve for the reorientation. In this work we perform
      umbrella sampling simulations to calculate the potential of mean force (PMF) for
      the reorientation of melittin from a surface-bound state to a transmembrane state
      and provide a molecular level insight in understanding the peptide-lipid
      properties that influence the existence of the free energy barrier. The PMFs were
      calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that
      the free energy barrier is reduced when the P/L ratio increases. In addition, we
      study the cooperative effect; specifically we investigate if the reorientation
      barrier is smaller for a second melittin, given that another neighboring melittin
      was already in the transmembrane orientation. We observe that indeed the barrier
      of the PMF curve is reduced in this case, thus confirming the presence of a
      cooperative effect. 

PMID- 24117277
TI  - Impact of organic carbon on the biodegradation of estrone in mixed culture
      systems.
AB  - The effects of organic carbon concentrations and loading on the degradation of
      estrone (E1) were examined under various conditions in batch reactors and
      membrane-coupled bioreactors (MBRs). Experiments examined effects on individual
      microorganisms (substrate competition and growth) and on the whole community
      (selection). Substrate competition with organic carbon (competitive inhibition
      and catabolic repression) was not a factor in E1 degradation (P = 0.19 and 0.29
      for two different analyses). Conversely, addition of organic carbon increased E1
      degradation rates, attributable to biomass growth in feast-famine reactors over a
      five-day period (P = 0.016). Subsequently, however, community dynamics controlled
      E1 degradation rates, with other organisms outcompeting E1 degraders. More
      moderate but sustained increases in E1 degradation rates were observed under
      starvation conditions. Low influent organic carbon strength was detrimental to E1
      degradation in MBRs, where organic carbon concentration and loading were
      decoupled (P = 0.018). These results point to the importance of multiple
      substrate utilizers in E1 degradation. They also suggest that while initial
      growth of biomass depends on the presence of sufficient organic carbon, further
      enrichment under starvation conditions may improve E1 degradation capability via
      the growth and/or stimulation of multiple substrate utilizers rather than
      heterotrophs characterized by an r-strategist growth regime. 

PMID- 24117278
TI  - Coumarin and furanocoumarin quantitation in citrus peel via ultraperformance
      liquid chromatography coupled with mass spectrometry (UPLC-MS).
AB  - Coumarins and furanocoumarins are secondary metabolites commonly found in citrus
      plants. These molecules are allelochemical compounds in plants that have
      controversial effects on humans, such as phototoxicity and the commonly described
      interactions with drugs, referred to as the "grapefruit juice effect". Thus, it
      is important to develop a reliable method to identify and quantitate the
      coumarins and furanocoumarins in citrus extracts. For this purpose, we herein
      describe an ultraperformance liquid chromatography coupled with mass spectrometry
      (UPLC-MS)-based method. We first developed a rapid UPLC method (20 min) to
      separate the isomers of each furanocoumarin. A subsequent single ion monitoring
      MS detection method was performed to distinguish between the molecules, which
      were possibly coeluting but had different molecular weights. The method was
      successfully used to separate and quantitate 6 coumarins and 21 furanocoumarins
      in variable amounts within peel extracts (flavedo and albedo) of 6 varieties of
      Citrus (sweet orange, lemon, grapefruit, bergamot, pummelo, and clementine). This
      method combines high selectivity and sensitivity in a rapid analysis and is
      useful for fingerprinting Citrus species via their coumarin and furanocoumarin
      contents. 

PMID- 24117279
TI  - Cutaneous dirt-adherent disease on a base of pemphigus erythematosus.

PMID- 24117280
TI  - Clearance of BRAF inhibitor-associated keratoacanthomas by systemic retinoids.

PMID- 24117281
TI  - Adverse outcomes associated with media exposure to contradictory nutrition
      messages.
AB  - There is increasing concern that the media present conflicting health information
      on topics including cancer screening and nutrition. Although scholars have
      speculated that exposure to this information leads to increased public confusion,
      less trust in health recommendations, and less engagement in health behaviors,
      there is a lack of empirical research that directly addresses the role of media
      exposure to conflicting information. Using data from the Annenberg National
      Health Communication Survey, this study finds that exposure to conflicting
      information on the health benefits and risks of, for example, wine, fish, and
      coffee consumption is associated with confusion about what foods are best to eat
      and the belief that nutrition scientists keep changing their minds. There is
      evidence that these beliefs, in turn, may lead people to doubt nutrition and
      health recommendations more generally-including those that are not rife with
      contradictory information (e.g., fruit/vegetable consumption, exercise). The
      implications of these findings for healthy eating campaigns and interventions are
      discussed. 

PMID- 24117282
TI  - Fusion of the additional sex combs like 1 and teashirt zinc finger homeobox 2
      genes resulting from ider(20q) aberration in a patient with myelodysplastic
      syndrome.

PMID- 24117283
TI  - Skilled nursing facility admissions of nursing home residents with advanced
      dementia.
AB  - OBJECTIVES: To describe the extent to which hospitalized nursing home (NH)
      residents with advanced dementia were admitted to a skilled nursing facility
      (SNF) after a qualifying hospitalization and to identify resident and nursing
      home characteristics associated with a greater likelihood of SNF admissions.
      DESIGN: Cohort study using data from the Minimum Data Set, Medicare claims, and
      the On-line Survey Certification of Automated Records. SETTING: United States,
      2000-2006. PARTICIPANTS: Nursing home residents with advanced dementia aged 65
      and older with a 3-day hospitalization (N = 4,177). MEASUREMENTS: The likelihood
      of SNF admission after hospitalization was calculated. Resident and nursing home
      factors associated with SNF admission were identified using hierarchical
      multivariable logistic regression. RESULTS: Sixty-one percent of residents with
      advanced dementia were admitted to a SNF after their hospitalization.
      Percutaneous endoscopic gastrostomy (PEG) tube placement during hospitalization
      was strongly associated with SNF admission (adjusted odds ratio (AOR) = 2.31, 95%
      confidence interval (CI) = 1.85-2.88), as was better functional status (AOR =
      1.21, 95% CI = 1.05-1.38). The presence of diabetes mellitus was associated with
      lower likelihood of SNF admission (AOR = 0.85, 95% CI = 0.73-0.99). Facility
      features significantly associated with SNF admission included more than 100 beds
      (AOR = 1.25, 95% CI = 1.07-1.46), being part of a chain (AOR = 1.31, 95% CI =
      1.14-1.50), urban location (AOR = 1.21, 95% CI = 1.03-1.41), and for-profit
      status (AOR = 1.28, 95% CI = 1.09-1.51). CONCLUSION: The majority of nursing home
      residents with advanced dementia are admitted to SNFs after a qualifying
      hospitalization. SNF admission is strongly associated with PEG tube insertion
      during hospitalization and with nursing home factors. Efforts to optimize
      appropriate use of SNF services in individuals with advanced dementia should
      focus on these factors.

PMID- 24117284
TI  - Practice-based learning can improve osteoporosis care.
AB  - OBJECTIVES: To examine physician engagement in practice-based learning using a
      self-evaluation module to assess and improve their care of individuals with or at
      risk of osteoporosis. DESIGN: Retrospective cohort study. SETTING: Internal
      medicine and subspecialty clinics. PARTICIPANTS: Eight hundred fifty U.S.
      physicians with time-limited certification in general internal medicine or a
      subspecialty. MEASUREMENTS: Performance rates on 23 process measures and seven
      practice system domain scores were obtained from the American Board of Internal
      Medicine (ABIM) Osteoporosis Practice Improvement Module (PIM), an Internet-based
      self-assessment module that physicians use to improve performance on one targeted
      measure. Physicians remeasured performance on their targeted measures by
      conducting another medical chart review. RESULTS: Variability in performance on
      measures was found, with observed differences between general internists,
      geriatricians, and rheumatologists. Some practice system elements were modestly
      associated with measure performance; the largest association was between
      providing patient-centered self-care support and documentation of calcium intake
      and vitamin D estimation and counseling (correlation coefficients from 0.20 to
      0.28, Ps < .002). For all practice types, the most commonly selected measure
      targeted for improvement was documentation of vitamin D level (38% of
      physicians). On average, physicians reported significant and large increases in
      performance on measures targeted for improvement. CONCLUSION: Gaps exist in the
      quality of osteoporosis care, and physicians can apply practice-based learning
      using the ABIM PIM to take action to improve the quality of care.

PMID- 24117285
TI  - Cumulative incidence of functional decline after minor injuries in previously
      independent older Canadian individuals in the emergency department.
AB  - OBJECTIVES: To estimate the cumulative incidence of functional decline in
      independent older adults 3 and 6 months after a minor injury treated in the
      emergency department (ED) and to identify predictors of this functional decline.
      DESIGN: Prospective cohort study. SETTINGS: Three Canadian teaching EDs.
      PARTICIPANTS: Individuals aged 65 and older who were independent in basic
      activities of daily living before their injury and were evaluated in the ED for
      minor injuries (N = 335). MEASUREMENTS: Functional decline was defined as a loss
      of 2 or more out of 28 points on the self-reported Older Americans Resources
      Services scale. Sociodemographic, mobility, and clinical risk factors for
      functional decline in non-ED studies were measured at the ED visit and 3 and 6
      months after the injury. Generalized linear mixed models were used to explore
      differences in functional decline between groups determined according to the
      different factors. RESULTS: The cumulative incidence of decline was 14.9% (95%
      confidence interval (CI) = 7.6-29.1%) at 3 months and 17.3% (95% CI = 9.7-30.9%)
      at 6 months. Predictors of functional decline were occasional use of a walking
      aid (relative risk (RR)=2.4, 95% CI = 1.4-4.2), needing help in instrumental
      activities of daily living (IADLs) before the injury (RR = 3.1, 95% CI=1.7-5.5),
      taking five or more daily medications (RR = 1.8, 95% CI = 1.0-3.2), and the
      emergency physicians' assessment of functional decline (RR = 2.8, 95% CI = 1.5
      5.3). CONCLUSION: Minor injuries in independent older adults treated in EDs are
      associated with a 15% cumulative incidence of functional decline 3 months after
      the injury that persisted 6 months later. Simple-to-measure factors such as
      occasional use of a walking aid, daily medication, need for help with IADLs, and
      physician assessment of decline may help identify independent older adults at
      risk of functional decline during their consultation. These results confirm the
      need to improve risk assessment and management of this population in EDs.

PMID- 24117286
TI  - Nonmotor symptoms in nursing home residents with Parkinson's disease: prevalence
      and effect on quality of life.
AB  - OBJECTIVES: To determine the prevalence of nonmotor symptoms (NMS) in nursing
      home (NH) residents with Parkinson's disease (PD) and to establish the
      association with quality of life. DESIGN: Cross-sectional. SETTING: Nursing homes
      in the southeast of the Netherlands. PARTICIPANTS: Nursing home residents with PD
      and a Mini-Mental State Examination score of 18 or greater (N = 73; mean age
      78.7, disease duration 10 years, mainly Hoehn and Yahr Stages 4 (38%) and 5
      (49%)) underwent detailed examination to determine the prevalence of NMS.
      MEASUREMENTS: Validated instruments for PD-related NMS were used to examine the
      NH residents with PD. The overall burden of NMS, and autonomic problems in
      particular, were measured using the Non-Motor Symptoms Scale (NMSS). Depression,
      neuropsychiatric symptoms, sleep problems, cognitive dysfunction, and motor
      impairments were focused on in further detail using established clinimetric
      tests. Linear regression analysis was used to examine the relationship between
      these symptoms and quality of life, which was measured using the Parkinson's
      Disease Questionnaire (PDQ-8). RESULTS: The NMSS revealed a mean of nearly 13
      different NMS per resident. Autonomic problems (constipation, urinary urgency)
      were particularly prevalent (48-75% of residents). Depressive symptoms were
      present in 45%. The most prevalent neuropsychiatric symptoms other than
      depression were irritability and apathy. The most common sleep problems were
      overall poor nighttime sleep quality, daytime sleepiness, and nocturia. Cognitive
      problems were highly prevalent, and 77% of the residents met the criteria for PD
      related dementia. High scores were also obtained for motor impairments. Mean PDQ
      8 score was high, indicating poor quality of life. Poor quality of life was most
      strongly associated with the prevalence and severity of overall NMS burden
      (coefficient of determination = 0.45). CONCLUSION: Nonmotor symptoms were highly
      prevalent in NH residents with PD. Quality of life was poor, largely because of
      NMS. Because many NMS are potentially treatable, diagnosis and treatment of these
      severely affected individuals deserve more attention.

PMID- 24117287
TI  - Preferences and actual treatment of older adults at the end of life. A mortality
      follow-back study.
AB  - OBJECTIVES: To compare actual treatments with preferences for starting or
      forgoing treatment of older adults at the end of life. DESIGN: Mortality follow
      back study of relatives of deceased older adults. Preferences and actual
      treatment were studied for each of four treatments: starting or forgoing
      resuscitation (do not resuscitate), artificial nutrition and hydration (ANH),
      antibiotics, and artificial respiration. SETTING: Older adults in the
      Netherlands. PARTICIPANTS: Proxies of deceased members (in 2006-2009) of two
      cohorts representative of the older Dutch population (n = 168) and of people with
      an advance directive (n = 184). MEASUREMENTS: Relationship between preferred and
      actual treatment. RESULTS: In most individuals who preferred receiving treatment,
      this preference was followed (n = 2/2, resuscitation; 23/26, ANH; 33/38,
      antibiotics; 23/24, AR). In approximately half of the individuals who preferred
      that a treatment be forgone, the preference was followed (n = 6/13,
      resuscitation; 11/18, ANH; 3/5, antibiotics), except for artificial respiration
      (n = 1/8). The majority of people for whom no preference was known received
      treatment (n = 5/9, resuscitation; 19/33, ANH; 15/20, antibiotics; 8/13,
      artificial respiration). People with a known preference for receiving a specific
      treatment had a seven times higher chance of preference being followed than
      people with a known preference for forgoing that treatment. People with a known
      preference for forgoing a treatment had a six times higher chance of treatment
      being forgone than people having no known preference. CONCLUSION: Although
      concordance between preferred and actual treatment is high in older adults who
      prefer treatment and lower in people who prefer no treatment, making preferences
      for forgoing treatment known is useful because it increases the chance of
      treatments being forgone in those who wish so.

PMID- 24117288
TI  - Hospice use and public expenditures at the end of life in assisted living
      residents in a Florida Medicaid waiver program.
AB  - OBJECTIVES: To examine the association between hospice use and public
      expenditures in a sample of dually eligible assisted living (AL) residents at the
      end of life. DESIGN: A retrospective cohort study. SETTING: Florida AL
      facilities. PARTICIPANTS: Newly enrolled dually eligible older AL residents under
      Florida's Medicaid Assisted Living for the Elderly waiver program who died
      between January 2003 and December 2004 (N = 382). MEASUREMENTS: Individual
      sociodemographic characteristics were obtained from Florida's Medicaid
      comprehensive assessment data. Medicaid eligibility status, enrollment in the AL
      waiver programs, International Classification of Diseases, Ninth Revision,
      Clinical Modification, codes and Medicaid claims data were obtained from
      Florida's Medicaid payment agency. Individual characteristics and Medicare and
      Medicaid claims data were merged with vital statistics to determine diagnoses,
      date of death, hospice enrollment, and public expenditures. RESULTS: The mean age
      of the study sample was 84.8 (range 65-102); 71.5% were female, and 63.4% were
      white. During the average 9.6 months of follow-up, 35.6% of the sample enrolled
      in hospice, and the average hospice length of stay was 47.9 d; 73.3% of the
      sample had been admitted to a hospital, and 38.0% had been admitted to a nursing
      home. The generalized linear model showed that hospice use was not significantly
      associated with lower public expenditures (average marginal effect = -$1,127, 95%
      confidence interval = -$8,377, $6,122). CONCLUSION: Hospice use at the end of
      life may not be associated with lower public expenditures in older dually
      eligible AL residents. Future research should examine the association between
      hospice enrollment and the quality of end-of-life care.

PMID- 24117289
TI  - Strangers in strange lands: the serial transfer of individuals with severe
      dementia.

PMID- 24117290
TI  - Deteriorating functional status in older adults after emergency department
      evaluation of minor trauma--opportunities and pragmatic challenges.

PMID- 24117291
TI  - The triple aim: a golden opportunity for geriatrics.

PMID- 24117292
TI  - Forget-me-nots.

PMID- 24117293
TI  - Nocturnal polyuria in a nursing home and effect on quality of life.

PMID- 24117294
TI  - Symptom profiles in individuals aging with post-polio syndrome.

PMID- 24117295
TI  - Effects of resistance versus multicomponent training on body composition and
      functional fitness in institutionalized elderly women.

PMID- 24117296
TI  - Ambulatory assisted living fallers at greatest risk for head injury.

PMID- 24117297
TI  - Total protein level in cerebrospinal fluid is stable in elderly adults.

PMID- 24117298
TI  - Is comprehensive geriatric assessment a better 1-year mortality predictor than
      comorbidity and prognostic indices in hospitalized older adults?

PMID- 24117299
TI  - Thyroid-stimulating hormone and mortality in older people.

PMID- 24117300
TI  - Prevalence of influenza vaccination and associated factors in Chinese nursing
      home healthcare workers.

PMID- 24117301
TI  - Precipitating factors in younger and older adults with decompensated chronic
      heart failure: are they different?

PMID- 24117302
TI  - Lactobacillus in jelly enhances the effect of influenza vaccination in elderly
      individuals.

PMID- 24117303
TI  - Life-space mobility and quality of life in community-dwelling older people.

PMID- 24117304
TI  - Public stigma associated with dementia in a Chinese-American immigrant
      population.

PMID- 24117305
TI  - Analysis of feasibility and toxicity of radiotherapy in centenarians.

PMID- 24117306
TI  - Factors affecting the decision to provide artificial nutrition for elderly adults
      with oral intake difficulty.

PMID- 24117307
TI  - Prevalence of xerostomia and its relationship with underlying diseases,
      medication, and nutrition: a descriptive observational study.

PMID- 24117308
TI  - Mild hyponatremia is associated with impaired cognition and falls in community
      dwelling older persons.

PMID- 24117309
TI  - Supporting the Triple Aim: interprofessional chief resident in training program.

PMID- 24117310
TI  - Tubulointerstitial nephritis and uveitis syndrome in an older adult: a case
      report and review of the literature.

PMID- 24117311
TI  - Mycobacterium avium complex tenosynovitis manifesting as carpal tunnel syndrome
      in an elderly adult.

PMID- 24117312
TI  - The coffee bean sign and sigmoid volvulus in an elderly adult.

PMID- 24117313
TI  - Pacemaker extrusion: a rare clinical problem mainly in elderly adults.

PMID- 24117314
TI  - Readability of patient education information on the American Geriatrics Society
      Foundation's Health-in-Aging website.

PMID- 24117315
TI  - Response to the letter "Readability of patient education information on the
      American Geriatrics Society Foundation's Health-in-Aging website".

PMID- 24117316
TI  - Unappreciated side effects of antihypertensive therapy.

PMID- 24117318
TI  - Community health center efficiency: the role of grant revenues in health center
      efficiency.
AB  - OBJECTIVE: To test the relationship between external environments, organizational
      characteristics, and technical efficiency in federally qualified health centers
      (FQHCs). We tested the relationship between grant revenue and technical
      efficiency in FQHCs. DATA SOURCES/STUDY DESIGN: Secondary data were collected in
      each year from the Uniform Data System (UDS) on 644 eligible U.S.-based FQHCs
      between 2005 and 2007. The study employs a retrospective longitudinal cohort
      design with instrumental variables. PRINCIPAL FINDINGS: Increased grant revenues
      did not increase the probability that a health center would be on the efficiency
      frontier. However, increased grant revenues had a negative association with
      technical efficiency for health centers that were not fully efficient.
      CONCLUSION: If all health centers were operating efficiently, anywhere from 39 to
      45 million patient encounters could have been delivered instead of the actual
      total of 29 million in 2007. Policy makers should consider tying grant revenues
      to performance indicators, and future work is needed to understand the mechanisms
      through which diseconomies of scale are present in FQHCs.

PMID- 24117319
TI  - Practical and economical implementation of online H/D exchange in LC-MS.
AB  - Structural elucidation is an integral part of drug discovery and development. In
      recent years, due to acceleration of the drug discovery and development process,
      there is a significant need for highly efficient methodologies for structural
      elucidation. In this work, we devised and standardized a simple and economical
      online hydrogen-deuterium exchange methodology, which can be used for structure
      elucidation purposes. Deuterium oxide (D2O) was infused as a postcolumn addition
      using the syringe pump at the time of elution of the analyte. The obtained
      hydrogen/deuterium (H/D) exchange spectrum of the unknown analyte was compared
      with the nonexchanged spectrum, and the extent of deuterium incorporation was
      delineated by using an algorithm to deconvolute partial H/D exchange, which
      confirmed the number of labile hydrogen(s) in the analyte. The procedure was
      standardized by optimizing flow rates of LC output, D2O infusion, sheath gas, and
      auxiliary gas using the model compound sulfasalazine. The robustness of the
      methodology was demonstrated by performing sensitivity analysis of various
      parameters such as concentrations of analyte, effect of matrices, concentrations
      of aqueous mobile phase, and types of LC modifiers. The optimized technique was
      also applied to chemically diverse analytes and tested on various mass
      spectrometers. Moreover, utility of the technique was demonstrated in the areas
      of impurity profiling and metabolite identification, taking pravastatin-lactone
      and N-oxide desloratidine, as examples. 

PMID- 24117320
TI  - Native oligomerization determines the mode of action and biological activities of
      human cathelicidin LL-37.
AB  - LL-37 is a multifunctional component of innate immunity, with a membrane-directed
      antimicrobial activity and receptor-mediated pleiotropic effects on host cells.
      Sequence variations in its primate orthologues suggest that two types of
      functional features have evolved; human LL-37-like peptides form amphipathic
      helical structures and self-assemble under physiological conditions, whereas
      rhesus RL-37-like peptides only adopt this structure in the presence of bacterial
      membranes. The first type of peptide has a lower and more medium-sensitive
      antimicrobial activity than the second type, but an increased capacity to
      stimulate host cells. Oligomerization strongly affects the mode of interaction
      with biological membranes and, consequently, both cytotoxicity and receptor
      mediated activities. In the present study we explored the effects of LL-37 self
      association by using obligate disulfide-linked dimers with either parallel or
      antiparallel orientations. These had an increased propensity to form stacked
      helices in bulk solution and when in contact with either anionic or neutral model
      membranes. The antimicrobial activity against Gram-positive or Gram-negative
      bacteria, as well as the cytotoxic effects on host cells, strongly depended on
      the type of dimerization. To investigate the extent of native oligomerization we
      replaced Phe5 with the photoactive residue Bpa (p-benzoyl-L-phenylalanine),
      which, upon UV irradiation, enabled covalent cross-linking and allowed us to
      assess the extent of oligomerization in both physiological solution and in model
      membranes.

PMID- 24117321
TI  - The role of stress as a trigger for epileptic seizures: a narrative review of
      evidence from human and animal studies.
AB  - Stress is one of the most frequently self-identified seizure triggers in patients
      with epilepsy; however, most previous publications on stress and epilepsy have
      focused on the role of stress in the initial development of epilepsy. This
      narrative review explores the causal role of stress in triggering seizures in
      patients with existing epilepsy. Findings from human studies of psychological
      stress, as well as of physiologic stress responses in humans and animals, and
      evidence from nonpharmacologic interventions for epilepsy are considered. The
      evidence from human studies for stress as a trigger of epileptic seizures is
      inconclusive. Although retrospective self-report studies show that stress is the
      most common patient-perceived seizure precipitant, prospective studies have
      yielded mixed results and studies of life events suggest that stressful
      experiences only trigger seizures in certain individuals. There is limited
      evidence suggesting that autonomic arousal can precede seizures. Interventions
      designed to improve coping with stress reduce seizures in some individuals.
      Studies of physiologic stress using animal epilepsy models provide more
      convincing evidence. Exposure to exogenous and endogenous stress mediators has
      been found to increase epileptic activity in the brain and trigger overt
      seizures, especially after repeated exposure. In conclusion, stress is likely to
      exacerbate the susceptibility to epileptic seizures in a subgroup of individuals
      with epilepsy and may play a role in triggering "spontaneous" seizures. However,
      there is currently no strong evidence for a close link between stress and
      seizures in the majority of people with epilepsy, although animal research
      suggests that such links are likely. Further research is needed into the
      relationship between stress and seizures and into interventions designed to
      reduce perceived stress and improve quality of life with epilepsy. 

PMID- 24117323
TI  - Fabrication of highly transparent and conductive indium-tin oxide thin films with
      a high figure of merit via solution processing.
AB  - Deposition technology of transparent conducting oxide (TCO) thin films is
      critical for high performance of optoelectronic devices. Solution-based
      fabrication methods can result in substantial cost reduction and enable broad
      applicability of the TCO thin films. Here we report a simple and highly effective
      solution process to fabricate indium-tin oxide (ITO) thin films with high
      uniformity, reproducibility, and scalability. The ITO films are highly
      transparent (90.2%) and conductive (rho = 7.2 * 10(-4) Omega.cm) with the highest
      figure of merit (1.19 * 10(-2) Omega(-1)) among all the solution-processed ITO
      films reported to date. The high transparency and figure of merit, low sheet
      resistance (30 Omega/sq), and roughness (1.14 nm) are comparable with the
      benchmark properties of dc sputtering and can meet the requirements for most
      practical applications. 

PMID- 24117322
TI  - Scalable preparation of ultrathin silica-coated Ag nanoparticles for SERS
      application.
AB  - Silica-coated Ag nanoparticles (Ag@SiO2 NPs) have been successfully prepared by a
      scalable flame spray pyrolysis (FSP) technique with production rate up to 4 g/h
      in laboratory-scale. The ultrathin SiO2 shell, with a thickness 1 nm, not only
      effectively avoids the intersintering of Ag nanoparticles core at the high
      temperature, but also serves as a protective layer of the SERS-active
      nanostructure. The silica-coated Ag nanoparticles form agglomerates in the large
      temperature gradient zone, which with several nanometers gaps from each other but
      not contact. Such an intriguing feature can result in more Raman hot-spots
      generated at the gaps among Ag core active sites, which will beneficial for the
      whole SERS substrate enhancement. The results demonstrate that a maximum
      enhancement factor can reach ~10(5) with a detectable concentration as low as 10(
      10) M for rhodamine 6G (R6G) molecules, indicating that the as-obtained unique
      nanostructure will be a promising candidate for SERS applications.

PMID- 24117325
TI  - Vaccines without borders to Latin America.

PMID- 24117324
TI  - Prevalence of vitamin D deficiency and association with functional status in
      newly admitted male veteran nursing home residents.
AB  - OBJECTIVES: To provide the first report on prevalence of vitamin D deficiency in
      newly admitted nursing home (NH) residents and associations with functional
      disabilities and chronic diseases. DESIGN: Retrospective chart review. SETTING:
      Nursing home (NH). PARTICIPANTS: Male veterans newly admitted to a NH for
      rehabilitation, skilled-nursing care, intermediate care, or respite care between
      January 2011 and June 2012. MEASUREMENTS: Total serum 25-hydroxyvitamin D
      (25(OH)D) levels were measured on admission. Vitamin D supplement users and those
      without 25(OH)D measurement within 7 days of admission were excluded, leaving an
      analytical sample of 104 residents. Vitamin D deficiency was defined as 25(OH)D
      less than 20 ng/mL. Data were collected on age, ethnicity, season, body mass
      index (BMI), functional disability in activities of daily living (ADLs)
      (mobility, bathing, dressing, toileting, continence, and feeding), and prevalent
      chronic diseases. RESULTS: Prevalence of vitamin D deficiency was 49.0%. In
      multivariate logistic regression models adjusted for age, ethnicity, and BMI,
      vitamin D deficiency was significantly associated with number of ADL disabilities
      (odds ratio (OR) = 1.4 for each 1-point increase in ADL disability score, P =
      .03) and prevalent diabetes mellitus (OR = 3.0, P = .03). In regression models
      using each ADL disability as a separate variable, only disability in feeding (OR
      = 4.7, P = .05) and diabetes mellitus (OR = 2.9, P = .04) remained significant.
      CONCLUSION: Almost half the individuals entering the NH and not taking vitamin D
      supplements had vitamin D deficiency. Greater number of ADL disabilities,
      disability in feeding, and prevalent diabetes mellitus were independently
      associated with vitamin D deficiency.

PMID- 24117326
TI  - Plasma anandamide and related n-acylethanolamide levels are not elevated in
      pregnancies complicated by hyperemesis gravidarum.
AB  - OBJECTIVES: Cannabinoids are effective antiemetics and the "endogenous
      cannabinoids" (endocannabinoids) are thought to modulate emesis in both humans
      and animal models. Endocannabinoids, their receptors and their metabolising
      enzymes are present in peripheral blood and a reduction in blood endocannabinoid
      concentration has been observed in individuals with excessive nausea and vomiting
      following parabolic flight manoeuvres. We tested the hypothesis that plasma
      endocannabinoid levels are similarly perturbed in women with hyperemesis
      gravidarum (HG), a condition where the aetiopathogenesis is still unknown,
      compared to normal pregnant controls. METHODS: Plasma N-arachidonoylethanolamine
      (anandamide), N-oleoylethanolamide and N-palmitoylethanolamide were quantified in
      women with HG (n = 15) and matched normal pregnant controls (n = 30) using UHPLC
      ESI-MS/MS utilising an isotope dilution method and selective ion monitoring.
      RESULTS: No significant differences in anandamide, oleoylethanolamide and
      palmitoylethanolamide levels were observed between the two groups. There were no
      significant correlations between these endocannabinoids and plasma haematocrit
      and serum urea or sodium concentrations. CONCLUSIONS: These results would suggest
      that either the circulating endocannabinoids quantified may not be key modulating
      factors in HG or that the expected endocannabinoid system response to the stress
      induced by nausea and vomiting of early pregnancy remain unchanged in women with
      HG.

PMID- 24117327
TI  - Assessing vividness of mental imagery: The Plymouth Sensory Imagery
      Questionnaire.
AB  - Mental imagery may occur in any sensory modality, although visual imagery has
      been most studied. A sensitive measure of the vividness of imagery across a range
      of modalities is needed: the shorter version of Bett's Questionnaire upon Mental
      Imagery (Sheehan, , J. Clin. Psychology, 23, 386) uses outdated items and has an
      unreliable factor structure. We report the development and initial validation of
      the Plymouth Sensory Imagery Questionnaire (Psi-Q) comprising items for each of
      the following modalities: Vision, Sound, Smell, Taste, Touch, Bodily Sensation,
      and Emotional Feeling. An exploratory factor analysis on a 35-item form indicated
      that these modalities formed separate factors, rather than a single imagery
      factor, and this was replicated by confirmatory factor analysis. The Psi-Q was
      validated against the Spontaneous Use of Imagery Scale (Reisberg et al., , Appl.
      Cogn. Psychology, 17, 147) and Marks' (, J. Mental Imagery, 19, 153) Vividness of
      Visual Imagery Questionnaire-2 (VVIQ-2). A short 21-item form comprising the best
      three items from the seven factors correlated with the total score and subscales
      of the full form, and with the VVIQ-2. Inspection of the data shows that while
      visual and sound imagery is most often rated as vivid, individuals who rate one
      modality as strong and the other as weak are not uncommon. Findings are
      interpreted within a working memory framework and point to the need for further
      research to identify the specific cognitive processes underlying the vividness of
      imagery across sensory modalities.

PMID- 24117328
TI  - Leadership, organization and teamwork for obstetrics and gynecology.

PMID- 24117329
TI  - Towards improving uterine electrical activity modeling and electrohysterography:
      ultrasonic quantification of uterine movements during labor.
AB  - The electrohysterogram is a potential new tool for diagnosing preterm labor.
      Parameters from the electrohysterogram may be influenced by uterine movement. An
      observational study was performed quantifying uterine movement during labor as a
      step towards improving electrohysterogram analysis for predicting preterm labor.
      The uterine wall was continuously tracked by ultrasound imaging during first
      stage of labor while an accelerometer recorded external abdominal accelerations
      in six women. A cyclic cranial-caudal movement of the uterine wall, caused by
      maternal respiration, was observed. This is reported and quantified for the first
      time. Average frequency, amplitude, and peak speed were 0.27 +/- 0.07 Hz, 0.68 +/
      0.84 cm, and 1.04 +/- 1.20 cm/s, respectively. The accelerometer signal
      correlated with uterine movement and therefore can possibly provide a reference
      for removing movement-induced artifacts. There is a need to model and measure the
      effect of uterine movement on the electrohysterogram parameters and make
      measurements more robust to movement artifacts. 

PMID- 24117330
TI  - Smoothing 3D protein structure motifs through graph mining and amino acid
      similarities.
AB  - One of the most powerful techniques to study proteins is to look for recurrent
      fragments (also called substructures), then use them as patterns to characterize
      the proteins under study. Although protein sequences have been extensively
      studied in the literature, studying protein three-dimensional (3D) structures can
      reveal relevant structural and functional information that may not be derived
      from protein sequences alone. An emergent trend consists of parsing proteins 3D
      structures into graphs of amino acids. Hence, the search of recurrent
      substructures is formulated as a process of frequent subgraph discovery where
      each subgraph represents a 3D motif. In this scope, several efficient approaches
      for frequent 3D motif discovery have been proposed in the literature. However,
      the set of discovered 3D motifs is too large to be efficiently analyzed and
      explored in any further process. In this article, we propose a novel pattern
      selection approach that shrinks the large number of frequent 3D motifs by
      selecting a subset of representative ones. Existing pattern selection approaches
      do not exploit the domain knowledge. Yet, in our approach, we incorporate the
      evolutionary information of amino acids defined in the substitution matrices in
      order to select the representative 3D motifs. We show the effectiveness of our
      approach on a number of real datasets. The results issued from our experiments
      show that considering the substitution between amino acids allows our approach to
      detect many similarities between patterns that are ignored by current subgraph
      selection approaches, and that it is able to considerably decrease the number of
      3D motifs while enhancing their interestingness.

PMID- 24117331
TI  - The rearrangement of tert-butylperoxides for the construction of polysubstituted
      furans.
AB  - The Bronsted acid catalyzed rearrangement of tert-butyl peroxides provides a new
      strategy to construct 2,3-disubstituted furans via 1,2-aryl migration. In
      addition, tert-butyl peroxides could also be transformed into 2,3,5
      trisubstituted or 2,5-disubstituted furans through a sequence of base-catalyzed
      Kornblum-DelaMare rearrangements and acid-promoted Paal-Knorr reactions. 

PMID- 24117332
TI  - Mean platelet volume predicts outcome in patients with asymptomatic carotid
      artery disease.
AB  - BACKGROUND AND OBJECTIVE: Platelets play a pivotal role in atherothrombosis and
      are potentially involved in the pathogenesis of atherosclerosis. We investigated
      whether mean platelet volume (MPV) predicts clinical outcome and progression of
      atherosclerosis in patients with asymptomatic carotid artery disease. METHODS: We
      studied 1006 of 1268 prospectively collected consecutive patients with
      asymptomatic carotid atherosclerosis who were evaluated by duplex sonography.
      Patients were followed up clinically for the occurrence of a major adverse
      cardiovascular event (MACE), a composite of myocardial infarction, percutaneous
      coronary intervention, coronary artery bypass graft, stroke and death. RESULTS:
      During a median follow-up of 3.1 years (interquartile range, 2.5-3.5), a total of
      316 (31.5%) MACEs were recorded. Increased levels of MPV were significantly
      associated with increased risk of the occurrence of MACEs (adjusted hazard ratio
      [HR] for an increase in one standard deviation [SD] of MPV 1.22, confidence
      interval [CI] 1.05-1.35, P < 0.01). Patients with MPV levels above 11.8
      femtolitre (= fifth quintile) had a significantly higher event rate (41.3% vs.
      29.3%, P < 0.001) with an adjusted HR for MACEs of 1.65 (95% CI 1.26-2.16, P <
      0.001) compared with patients with MPV levels in the first to fourth quintile. No
      significant association was found between baseline MPV levels with either
      baseline degree or progression during a 6-month follow-up of carotid stenosis.
      CONCLUSION: Mean platelet volume was independently and significantly associated
      with adverse cardiovascular outcome in patients with asymptomatic carotid
      atherosclerosis.

PMID- 24117333
TI  - Validity of the ActiGraph GT1M during walking and cycling.
AB  - The ActiGraph activity monitors have developed and newer versions of the
      ActiGraph accelerometers (GT1M, GT3X and GT3X +) are now available, including
      changes in hardware and software compared to the old version (AM7164). This is
      problematic as most of the validation and calibration work includes the AM7164.
      The aims of the study were to validate the ActiGraph GT1M during level and graded
      walking and to assess the potential underestimation of physical activity during
      cycling. Data were obtained from 20 participants during treadmill walking and
      ergometer cycling. Energy expenditure was measured via indirect calorimetry and
      used as the criterion method. Activity counts were highly correlated with energy
      expenditure during level walking (R(2) = 0.82) and graded walking at 5% and 8%
      (R(2) = 0.82 and R(2) = 0.67, respectively). There was no linear relationship
      between activity counts and energy expenditure during cycling. The average
      activity counts for all data points during cycling was 1,157 counts per minute
      (CPM) (SD = 974), and mean energy expenditure was 5.0 metabolic equivalents. The
      GT1M is a valid tool for assessing walking across a wide range of speeds and
      gradients. However, there is no relationship between activity counts and energy
      expenditure during cycling and physical activity is underestimated by ~73% during
      cycling compared to walking.

PMID- 24117334
TI  - Shift in egg-laying strategy to avoid plant defense leads to reproductive
      isolation in mutualistic and cheating yucca moths.
AB  - Through the process of ecological speciation, insect populations that adapt to
      new host plant species or to different plant tissues could speciate if such
      adaptations cause reproductive isolation. One of the key issues in this process
      is identifying the mechanisms by which adaptation in ecological traits leads
      directly to reproductive isolation. Here I show that within a radiation of
      specialist moths that pollinate and feed on yuccas, shifts in egg placement
      resulted in changes in female moth egg-laying structures that led to concomitant
      changes in male reproductive morphology. As pollinator moths evolved to
      circumvent the ability of yuccas to selectively abscise flowers that contain
      pollinator eggs, ovipositor length became shorter. Because mating occurs through
      the ovipositor, shortening of the ovipositor also led to significantly shorter
      and wider male intromittent organs. In instances where two pollinator moth
      species occur in sympatry and on the same host plant species, there is one short
      and one long ovipositor species that are reproductively isolated. Given that many
      plant-feeding insects lay eggs into plant tissues, changes in ovipositor
      morphology that lead to correlated changes in reproductive morphology may be a
      mechanism that maintains reproductive isolation among closely related species
      using the same host plant species. 

PMID- 24117335
TI  - Shape memory polymer nanocomposites for application of multiple-field active
      disassembly: experiment and simulation.
AB  - Active disassembly (AD) uses innovative materials that can perform a designed
      disassembly action by the application of an external field. AD provides
      improvements over current disassembly processes by limiting machine or manual
      labor and enabling batch processing for end-of-life products. With improved
      disassembly operations, more reuse of components and purer recycling streams may
      be seen. One problem with AD, however, has been with the single-field actuation
      because of the probability of accidental disassembly. This presentation will
      discuss the application of shape memory polymer (SMP) nanocomposites in a new AD
      process. This novel AD process requires multiple-field actuation of the SMP
      nanocomposite fastener. In the analysis of this AD process, thermal and magnetic
      field tests were performed on the SMP nanocomposite. From these tests, finite
      element analysis was performed to model and simulate the multiple-field AD
      process. The results of the simulations provide performance variables for the AD
      process and show a better performance time for the SMP nanocomposite fastener
      than for a comparable SMP fastener. 

PMID- 24117336
TI  - Multiple linear leiomyomas of the forehead as the presenting sign of Reed
      syndrome.
AB  - A 62-year-old female presented with a linear arrangement of multiple
      asymptomatic, discrete, dome-shaped, smooth, skin-colored papules and nodules
      involving the left forehead. Histopathology showed a poorly circumscribed nodule
      of haphazardly arranged fascicles of smooth muscle cells involving the papillary
      and superficial reticular dermis. Genetic testing revealed the patient to be
      heterozygous for the R233H mutation in the fumarate hydratase gene. Clinical,
      microscopic, and genetic findings were consistent with a diagnosis of Reed
      syndrome. Reed syndrome is a rare disorder defined by cutaneous and uterine
      leiomyomas and, uncommonly, renal cell carcinoma. 

PMID- 24117337
TI  - Online LC-GC analysis of free sterols/stanols and intact steryl/stanyl esters in
      cereals.
AB  - The suitability of online liquid chromatography-gas chromatography for the
      analysis of free sterols/stanols, steryl/stanyl fatty acid esters, and trans
      steryl/stanyl ferulic acid esters in cereals is demonstrated. The silylated lipid
      extracts were fractionated via liquid chromatography on a normal phase, and the
      fractions containing the sterol classes were transferred online to the gas
      chromatograph for the analysis of their individual compositions. The study
      provides for the first time data on free sterols/stanols and intact steryl/stanyl
      esters in sweet corn, popcorn, and proso millet. Sweet corn revealed the highest
      contents of free sterols/stanols and steryl/stanyl fatty acid esters, and
      popcorn, in turn, the highest amounts of trans-steryl/stanyl ferulic acid esters.
      The distribution patterns of the proso millet samples revealed pronounced
      differences from those of sweet corn and popcorn as they particularly exhibited
      high proportions of free cholesterol and cholesteryl fatty acid esters.
      Furthermore, no trans-steryl/stanyl ferulic acid esters could be detected. 

PMID- 24117339
TI  - Screening for tinea unguium by Dermatophyte Test Strip.
AB  - BACKGROUND: The direct microscopy, fungal culture and histopathology that are
      necessary for the definitive diagnosis of tinea unguium are disadvantageous in
      that detection sensitivity is affected by the level of skill of the person who
      performs the testing, and the procedures take a long time. OBJECTIVES: The
      Dermatophyte Test Strip, which was developed recently, can simply and easily
      detect filamentous fungi in samples in a short time, and there are expectations
      for its use as a method for tinea unguium screening. With this in mind, we
      examined the detection capacity of the Dermatophyte Test Strip for tinea unguium.
      METHODS: The presence or absence of fungal elements was judged by direct
      microscopy and Dermatophyte Test Strip in 165 nail samples obtained from
      residents in nursing homes for the elderly. Moreover, the minimum sample amount
      required for positive determination was estimated using 32 samples that showed
      positive results by Dermatophyte Test Strip. RESULTS: The Dermatophyte Test Strip
      showed 98% sensitivity, 78% specificity, 84.8% positive predictive value, 97%
      negative predictive value and a positive and negative concordance rate of 89.1%.
      The minimum sample amount required for positive determination was 0.002-0.722 mg.
      CONCLUSIONS: The Dermatophyte Test Strip showed very high sensitivity and
      negative predictive value, and was considered a potentially useful method for
      tinea unguium screening. Positive determination was considered to be possible
      with a sample amount of about 1 mg.

PMID- 24117338
TI  - Origin of the unique morphology of the shoulder girdle in turtles.
AB  - The shoulder girdle of turtles has a triradiate morphology. Although its dorsal
      process represents the scapular blade, the skeletal identities of the two ventral
      processes remain uncertain. To elucidate the question, developmental patterns of
      the girdles were compared between Chinese soft-shelled turtles, chickens, and
      mice. Despite the morphological diversity of adults, the initial primordia of the
      shoulder girdles showed similar morphological patterns. The ventral two processes
      developed from the anlagen comparable to those of the acromion and the coracoid
      in other amniotes. The developmental pattern of the acromion is very similar
      among embryos, whereas that of the coracoid in mammals differs from that in non
      mammals, implying that coracoids are not homologous between non-mammals and
      mammals. Therefore, amniotes have retained the ancestral pattern of the girdle
      anlage, and the shoulder girdle of turtles has been achieved through a
      transformation of the pattern in the late ontogenic period. 

PMID- 24117340
TI  - Impact of glucose-6-phosphate dehydrogenase deficiency on sickle cell anaemia
      expression in infancy and early childhood: a prospective study.
AB  - In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate
      dehydrogenase (G6PD) deficiency is usually described as having no effect and only
      occasionally as increasing severity. We analysed sequential clinical and
      biological data for the first 42 months of life in SCA patients diagnosed by
      neonatal screening, including 27 G6PD-deficient patients, who were matched on
      sex, age and parents' geographic origin to 81 randomly selected patients with
      normal G6PD activity. In the G6PD-deficient group, steady-state haemoglobin was
      lower (-6.2 g/l, 95% confidence interval (CI), [-10.1; -2.3]) and reticulocyte
      count higher (247 * 10(9) /l, 95%CI, [97; 397]). The acute anaemic event rate was
      3 times higher in the G6PD-deficient group (P < 10(-3) ). A higher proportion of
      G6PD-deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%],
      P < 10(-3) ), for acute anaemic events, and also vaso-occlusive and infectious
      events. No significant between-group differences were found regarding the rates
      of vaso-occlusive, infectious, or cerebrovascular events. G6PD deficiency in
      babies with SCA worsens anaemia and increases blood transfusion requirements in
      the first years of life. These effects decrease after 2 years of age, presumably
      as the decline in fetal haemoglobin levels leads to increased sickle cell
      haemolysis and younger red blood cells with higher G6PD activity. 

PMID- 24117341
TI  - Microfluidic chip with integrated electrical cell-impedance sensing for
      monitoring single cancer cell migration in three-dimensional matrixes.
AB  - Cell migration has been recognized as one hallmark of malignant tumor
      progression. By integrating the method of electrical cell-substrate impedance
      sensing (ECIS) with the Boyden chamber design, the state-of-the-art techniques
      provide kinetic information about cell migration and invasion processes in three
      dimensional (3D) extracellular matrixes. However, the information related to the
      initial stage of cell migration with single-cell resolution, which plays a unique
      role in the metastasis-invasion cascade of cancer, is not yet available. In this
      paper, we present a microfluidic device integrated with ECIS for investigating
      single cancer cell migration in 3D matrixes. Using microfluidics techniques
      without the requirement of physical connections to off-chip pneumatics, the
      proposed sensor chip can efficiently capture single cells on microelectrode
      arrays for sequential on-chip 2D or 3D cell culture and impedance measurement. An
      on-chip single-cell migration assay was successfully demonstrated within several
      minutes. Migration of single metastatic MDA-MB-231 cells in their initial stage
      can be monitored in real time; it shows a rapid change in impedance magnitude of
      approximately 10 Omega/s, whereas no prominent impedance change is observed for
      less-metastasis MCF-7 cells. The proposed sensor chip, allowing for a rapid and
      selective detection of the migratory properties of cancer cells at the single
      cell level, could be applied as a new tool for cancer research. 

PMID- 24117342
TI  - Mental health and high-cost health care utilization: new evidence from Axis II
      disorders.
AB  - OBJECTIVE: To analyze the associations between Axis II (A2) disorders and two
      measures of health care utilization with relatively high cost: emergency
      department (ED) episodes and hospital admissions. DATA SOURCE/STUDY SETTING: Wave
      I (2001/2002) and Wave II (2004/2005) of the National Longitudinal Survey on
      Alcohol and Related Conditions (NESARC). STUDY DESIGN: A national probability
      sample of adults. Gender-stratified regression analysis adjusted for a range of
      covariates associated with health care utilization. DATA COLLECTION: The target
      population of the NESARC is the civilian noninstitutionalized population aged 18
      years and older residing in the United States. The cumulative survey response
      rate is 70.2 percent with a response rate of 81 percent (N=43,093) in Wave I and
      86.7 percent (N=34,653) in Wave II. PRINCIPAL FINDINGS: Both men and women with
      A2 disorders are at elevated risk for ED episodes and hospital admissions.
      Associations are robust after adjusting for a rich set of confounding factors,
      including Axis I (clinical) psychiatric disorders. We find evidence of a dose
      response relationship, while antisocial and borderline disorders exhibit the
      strongest associations with both measures of health care utilization.
      CONCLUSIONS: This study provides the first published estimates of the
      associations between A2 disorders and high-cost health care utilization in a
      large, nationally representative survey. The findings underscore the potential
      implications of these disorders on health care expenditures.

PMID- 24117344
TI  - Educating young men about testicular cancer: support for a comprehensive
      testicular cancer campaign.
AB  - Despite the prevalence of testicular cancer among men 15-39 years of age, little
      has been done to increase awareness of this disease or educate males about its
      prevention. To fill this gap, the Standard Model of Health Communication was
      incorporated to design and implement a comprehensive testicular cancer campaign
      among male college students. To test the effectiveness of these messages, college
      students (N = 220) completed measures before and after the campaign. In addition,
      the authors obtained a control group of male college students (N = 52) who were
      not exposed to the messages. Survey items assessed awareness of testicular cancer
      and behaviors related to testicular cancer. Participants' knowledge of testicular
      cancer and likelihood of conducting a testicular self-exam increased
      significantly after being exposed to the campaign information. Men who were
      exposed to testicular cancer messages were more knowledgeable about testicular
      cancer and were more likely to conduct testicular self-examinations than were men
      in the control group. 

PMID- 24117343
TI  - Effects of severing the corpus callosum on electrical and BOLD functional
      connectivity and spontaneous dynamic activity in the rat brain.
AB  - Functional networks, defined by synchronous spontaneous blood oxygenation level
      dependent (BOLD) oscillations between spatially distinct brain regions, appear to
      be essential to brain function and have been implicated in disease states,
      cognitive capacity, and sensing and motor processes. While the topographical
      extent and behavioral function of these networks has been extensively
      investigated, the neural functions that create and maintain these
      synchronizations remain mysterious. In this work callosotomized rodents are
      examined, providing a unique platform for evaluating the influence of structural
      connectivity via the corpus callosum on bilateral resting state functional
      connectivity. Two experimental groups were assessed, a full callosotomy group, in
      which the corpus callosum was completely sectioned, and a sham callosotomy group,
      in which the gray matter was sectioned but the corpus callosum remained intact.
      Results indicated a significant reduction in interhemispheric connectivity in the
      full callosotomy group as compared with the sham group in primary somatosensory
      cortex and caudate-putamen regions. Similarly, electrophysiology revealed
      significantly reduced bilateral correlation in band limited power. Bilateral
      gamma Band-limited power connectivity was most strongly affected by the full
      callosotomy procedure. This work represents a robust finding indicating the
      corpus callosum's influence on maintaining integrity in bilateral functional
      networks; further, functional magnetic resonance imaging (fMRI) and
      electrophysiological connectivity share a similar decrease in connectivity as a
      result of the callosotomy, suggesting that fMRI-measured functional connectivity
      reflects underlying changes in large-scale coordinated electrical activity.
      Finally, spatiotemporal dynamic patterns were evaluated in both groups; the full
      callosotomy rodents displayed a striking loss of bilaterally synchronous
      propagating waves of cortical activity.

PMID- 24117345
TI  - Molecular analysis of ATP-sensitive K+ channel subunits expressed in mouse vas
      deferens myocytes.
AB  - BACKGROUND AND PURPOSE: ATP-sensitive K(+)(K(ATP)) channels, which are composed
      of K(IR)6.x associated with sulphonylurea receptor (SUR) subunits, have been
      detected in native smooth muscle cells, but it is currently not known which of
      these is expressed in mouse vas deferens myocytes. EXPERIMENTAL APPROACH:
      Pharmacological and electrophysiological properties of K(ATP) channels in mouse
      vas deferens myocytes were investigated using patch clamp techniques. Molecular
      biological analyses were performed to examine the properties of these K(ATP)
      channels. KEY RESULTS: During conventional whole-cell recording, pinacidil
      elicited an inward current that was suppressed by glibenclamide, a sulfonylurea
      agent, and by U-37883A, a selective K(IR)6.1 blocker. When 0.3 mM ATP was added
      to the pipette solution, the peak amplitude of the pinacidil-induced current was
      much smaller than that recorded in its absence. When 3 mM UDP, GDP or ADP was
      included in the pipette solution, an inward current was elicited after
      establishment of the conventional whole-cell configuration, with potency order
      being UDP > GDP > ADP. These nucleoside diphosphate-induced inward currents were
      suppressed by glibenclamide. MCC-134, a SUR modulator, induced glibenclamide
      sensitive K(ATP) currents that were similar to those induced by 100 MUM
      pinacidil. In the cell-attached configuration, pinacidil activated channels with
      a conductance similar to that of K(IR)6.1. Reverse transcription PCR analysis
      revealed the expression of K(IR)6.1 and SUR2B transcripts and immunohistochemical
      studies indicated the presence of K(IR)6.1 and SUR2B proteins in the myocytes.
      CONCLUSIONS AND IMPLICATIONS: Our results indicate that native K(ATP) channels in
      mouse vas deferens myocytes are a heterocomplex of K(IR)6.1 channels and SUR2B
      subunits.

PMID- 24117346
TI  - Genetic variation and gender determine bradykinin type 1 receptor responses in
      human tissue: implications for the ACE-inhibitor-induced effects in patients with
      coronary artery disease.
AB  - The efficacy of the ACE (angiotensin-converting enzyme) inhibitor perindopril in
      coronary artery disease [EUROPA (European trial on reduction of cardiac events
      with perindopril in stable coronary artery disease) study] is associated with the
      rs12050217 A/G single nucleotide polymorphism in the B1 receptor (bradykinin type
      1 receptor) gene. To investigate the underlying mechanism, we examined the effect
      of this polymorphism on B1-receptor-mediated coronary artery dilation and
      peripheral blood mononuclear cell activation. Vasorelaxant responses of human
      coronary microarteries from subjects without coronary disease to des-Arg(9)
      bradykinin and to bradykinin were studied in organ bath experiments. Des-Arg9
      bradykinin responses were endothelium-dependent and exclusively mediated by B1
      receptors, whereas responses to bradykinin were induced through B2 receptors
      (bradykinin type 2 receptors). The presence of the G allele reduced the response
      to 3 * 10(-8) mol/l des-Arg(9)-bradykinin by 29% [AA (n=13) compared with AG/GG
      (n=8); P<0.03], and tended to lower concentration-related responses (P=0.065) to
      this agonist, whereas the responses to bradykinin were unaffected by the
      rs12050217 genotype. In freshly obtained human mononuclear cells 1 MUmol/l des
      Arg(9)-bradykinin increased expression of the pro-inflammatory factors CXCL5 (CXC
      chemokine ligand 5) and IL6 (interleukin-6). These responses were not affected by
      genotype and exclusively occurred in blood cells from women, correlating (in the
      case of CXCL5) with their plasma 17beta-oestradiol levels (r(2)=0.32, P=0.02;
      n=17). IL-1beta (interleukin-1beta) increased CXCL5 and IL6 expression in both
      genders, and this response was not associated with 17beta-oestradiol levels. The
      gender difference in responses to B1 receptor stimulation in blood mononuclear
      cells implies possible gender differences in the response to ACE inhibitor
      therapy, which needs to be studied more comprehensively. The observed decrease in
      coronary vasodilator response might contribute to the impaired treatment response
      to perindopril of G allele carriers found in the EUROPA study.

PMID- 24117348
TI  - Tea consumption and depressive symptoms in older people in rural China.
AB  - OBJECTIVES: To examine the association between tea consumption and depressive
      symptoms in Chinese older people and to explore the mediating role of
      cerebrovascular disease in the association. DESIGN: Population-based cross
      sectional study. SETTING: A rural community near Qufu in Shandong, China.
      PARTICIPANTS: Community-dwelling individuals aged 60 and older (mean 68.6; 59.3%
      female) from the Confucius Hometown Aging Project (N = 1,368). MEASUREMENTS: Data
      were collected through interviews, clinical examinations, and psychological
      testing, following a standard procedure. Presence of high depressive symptoms was
      defined as a score of 5 or greater on the 15-item Geriatric Depression Scale.
      RESULTS: Of the 1,368 participants, 165 (12.1%) were weekly and 489 (35.7%) were
      daily tea consumers. Compared with no or irregular tea consumption, controlling
      for age, sex, education, leisure activities, number of comorbidities, and Mini
      Mental State Examination score, the odds ratios of having high depressive
      symptoms were 0.86 (95% confidence interval (CI) = 0.56-1.32) for weekly and 0.59
      (95% CI = 0.43-0.81) for daily tea consumption (P for linear trend = .001); the
      linear trend of the association remained statistically significant when further
      controlling for history of stroke, transient ischemic attacks, and presence of
      carotid plaques. CONCLUSIONS: Daily tea consumption is associated with a lower
      likelihood of depressive symptoms in Chinese older people living in a rural
      community. The association appears to be independent of cerebrovascular disease
      and atherosclerosis.

PMID- 24117347
TI  - AMPA receptor antagonist NBQX attenuates later-life epileptic seizures and
      autistic-like social deficits following neonatal seizures.
AB  - PURPOSE: To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent
      early mammalian target of rapamycin (mTOR) pathway activation and long-term
      sequelae following neonatal seizures in rats, including later-life spontaneous
      recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits.
      METHODS: Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at
      postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS
      (every 12 h * 4 doses). Twelve hours post-HS, we assessed mTOR activation marker
      phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS
      + V) or NBQX-treated post-HS rats (HS + N) versus littermate controls (C + V).
      Spontaneous seizure activity was compared between groups by epidural cortical
      electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was
      measured using Timm staining. Finally, we assessed behavior between P30 and P38.
      KEY FINDINGS: Postseizure NBQX treatment significantly attenuated seizure-induced
      increases in p-p70S6K in the hippocampus (p < 0.01) and cortex (p < 0.001).
      Although spontaneous recurrent seizures increased in adulthood in HS + V rats
      compared to controls (3.22 +/- 1 seizures/h; p = 0.03), NBQX significantly
      attenuated later-life seizures (0.14 +/- 0.1 seizures/h; p = 0.046). HS + N rats
      showed less aberrant mossy fiber sprouting (115 +/- 8.0%) than vehicle-treated
      post-HS rats (174 +/- 10%, p = 0.004), compared to controls (normalized to 100%).
      Finally, NBQX treatment prevented alterations in later-life social behavior; post
      HS rats showed significantly decreased preference for a novel over a familiar rat
      (71.0 +/- 12 s) compared to controls (99.0 +/- 15.6 s; p < 0.01), whereas HS + N
      rats showed social novelty preference similar to controls (114.3 +/- 14.1 s).
      SIGNIFICANCE: Brief NBQX administration during the 48 h postseizure in P10 Long
      Evans rats suppresses transient mTOR pathway activation and attenuates
      spontaneous recurrent seizures, social preference deficits, and mossy fiber
      sprouting observed in vehicle-treated adult rats after early life seizures. These
      results suggest that acute AMPAR antagonist treatment during the latent period
      immediately following neonatal HS can modify seizure-induced activation of mTOR,
      reduce the frequency of later-life seizures, and protect against CA3 mossy fiber
      sprouting and autistic-like social deficits.

PMID- 24117349
TI  - Impact of electrostatics on the chemodynamics of highly charged metal-polymer
      nanoparticle complexes.
AB  - In this work, the impact of electrostatics on the stability constant, the rate of
      association/dissociation, and the lability of complexes formed between Cd(II),
      Pb(II), and carboxyl-modified polymer nanoparticles (also known as latex
      particles) of radius ~ 50 nm is systematically investigated via electroanalytical
      measurements over a wide range of pHs and NaNO3 electrolyte concentrations. The
      corresponding interfacial structure and key electrostatic properties of the
      particles are independently derived from their electrokinetic response,
      successfully interpreted using soft particle electrohydrodynamic formalism, and
      complemented by Forster resonance energy transfer (FRET) analysis. The results
      underpin the presence of an ~0.7-1 nm thick permeable and highly charged shell
      layer at the surface of the polymer nanoparticles. Their electrophoretic mobility
      further exhibits a minimum versus NaNO3 concentration due to strong polarization
      of the electric double layer. Integrating these structural and electrostatic
      particle features with recent theory on chemodynamics of particulate metal
      complexes yields a remarkable recovery of the measured increase in complex
      stability with increasing pH and/or decreasing solution salinity. In the case of
      the strongly binding Pb(II), the discrepancy at pH > 5.5 is unambiguously
      assigned to the formation of multidendate complexes with carboxylate groups
      located in the particle shell. With increasing pH and/or decreasing electrolyte
      concentration, the theory further predicts a kinetically controlled formation of
      metal complexes and a dramatic loss of their lability (especially for lead) on
      the time-scale of diffusion toward a macroscopic reactive electrode surface.
      These theoretical findings are again shown to be in agreement with experimental
      evidence. 

PMID- 24117350
TI  - An exploratory assessment of theory of mind and psychological impairment in
      patients with bulimia nervosa.
AB  - This study aimed to investigate psychosocial functioning and different dimensions
      of theory of mind (ToM) in people with bulimia nervosa (BN) and Eating Disorder
      Not Otherwise Specified-BN type (EDNOS-BN). Psychosocial functioning and ToM were
      assessed in a sample of young adult females, 16 BN and 16 EDNOS-BN outpatients
      and 16 healthy controls (HCs). They were assessed using the Eating Disorder
      Inventory-Symptom Checklist-2 (EDI-2 SC) for evaluating psychological traits
      associated with eating disorders; the Symptom Checklist-90-Revised (SCL-90-R) for
      evaluating psychopathological status; and the Theory of Mind Assessment Scale
      (Th.o.m.a.s.), a semi-structured interview aimed at assessing a person's
      different dimensions of ToM. The BN and EDNOS-BN groups exhibited worse
      performance than the control group on all dimensions of the SCL-90-R, and on all
      dimensions of the EDI-2 SC. The only difference for perfectionism was that BN
      obtained higher scores than EDNOS-BN group. Our results also revealed an
      impairment of third-person and second-order ToM in patients with bulimia (BN and
      EDNOS-BN) with respect to control subjects. These preliminary data have important
      implications for future empirical work, in that they provide valuable information
      regarding the importance of investigating the various facets of ToM ability
      separately, in order to provide a more detailed profile of ToM functioning in the
      clinical samples. 

PMID- 24117352
TI  - Redox-gated three-terminal organic memory devices: effect of composition and
      environment on performance.
AB  - The performance of redox-gated organic nonvolatile memory (NVM) based on
      conducting polymers was investigated by altering the polymer structure,
      composition, and local environment of three-terminal devices with a field-effect
      transistor (FET) geometry. The memory function was dependent on the presence of a
      redox active polymer with high conducting and low conducting states, the presence
      of a redox counter-reaction, and the ability to transport ions between the
      polymer and electrolyte phases. Simultaneous monitoring of both the "write"
      current and "readout" current revealed the switching dynamics of the devices and
      their dependence on the local atmosphere. Much faster and more durable response
      was observed in acetonitrile vapor than in a vacuum, indicating the importance of
      polar molecules for both ion motion and promotion of electrochemical reactions.
      The major factor determining "write" and "erase" speeds of redox-gated polymer
      memory devices was determined to be the rate of ion transport through the
      electrolyte layer to provide charge compensation for the conducting polarons in
      the active polymer layer. The results both confirm the mechanism of redox-gated
      memory action and identify the requirements of the conducting polymer, redox
      counter reaction, and electrolyte for practical applications as alternative solid
      state nonvolatile memory devices. 

PMID- 24117351
TI  - Assessing post-anterior cruciate ligament reconstruction ambulation using
      wireless wearable integrated sensors.
AB  - Abstract A hardware/software co-design for assessing post-Anterior Cruciate
      Ligament (ACL) reconstruction ambulation is presented. The knee kinematics and
      neuromuscular data during walking (2-6 km h(-1)) have been acquired using
      wireless wearable motion and electromyography (EMG) sensors, respectively. These
      signals were integrated by superimposition and mixed signals processing
      techniques in order to provide visual analyses of bio-signals and identification
      of the recovery progress of subjects. Monitoring overlapped signals
      simultaneously helps in detecting variability and correlation of knee joint
      dynamics and muscles activities for an individual subject as well as for a group.
      The recovery stages of subjects have been identified based on combined features
      (knee flexion/extension and EMG signals) using an adaptive neuro-fuzzy inference
      system (ANFIS). The proposed system has been validated for 28 test subjects
      (healthy and ACL-reconstructed). Results of ANFIS showed that the ambulation data
      can be used to distinguish subjects at different levels of recuperation after ACL
      reconstruction.

PMID- 24117353
TI  - Neuroanniversary 2013.

PMID- 24117355
TI  - Obituary: Frank Clifford Rose MD, FRCP (August 29, 1926 - November 1, 2012).

PMID- 24117356
TI  - Letter to the editor and author's response: megrim does not mean migrainous
      vertigo-a comment on Lardreau (2012 ).

PMID- 24117357
TI  - Author's response: evolution of a word (megrim) and language impoverishment-a
      response to Mr. Grzybowski and Mr. Larner's comment.

PMID- 24117361
TI  - Potential nonadiabatic reactions: ring-opening 4,6-dimethylidenebicyclo[3.1.0]hex
      2-ene derivatives to aromatic reactive intermediates.
AB  - Potential singlet-triplet surface crossings for the ring opening of 4,6
      dimethylidenebicyclo[3.1.0]hex-2-ene derivatives were explored using density
      functional theory (DFT) and complete active space self-consistent field (CASSCF)
      methods. Since these ring openings involve relatively high energy species that
      lead to relatively stable aromatic species, a good scenario for potential
      nonadiabatic events, we posited that the reaction paths of these ring openings
      might come close to or cross excited state surfaces. At the DFT level of theory,
      all reaction paths exhibited characteristics suggestive of singlet-triplet
      intersections along their paths. 6-Methylidenebicyclo[3.1.0]hex-3-en-2-one and a
      closely related derivative (4-methylidenebicyclo[3.1.0]hex-2-en-6-one) were
      explored at the CASSCF level of theory; CASSCF results were qualitatively similar
      to DFT results and yielded spin-orbit couplings of 1.1-1.4 cm(-1) at the singlet
      triplet crossing points. 

PMID- 24117362
TI  - Changing clinical expression of Behcet disease in Korea during three decades
      (1983-2012): chronological analysis of 3674 hospital-based patients.
AB  - BACKGROUND: Behcet disease (BD) is a chronic multisystemic vasculitis affecting
      blood vessels of any calibre or type. Recent evidence suggests that the clinical
      expression of BD is lessening. OBJECTIVES: To examine the clinical expression of
      BD in Korea during the past three decades via a large patient registry. METHODS:
      Initial manifestations of patients with BD seen at a tertiary referral hospital
      between 1983 and 2012 were reviewed retrospectively, stratifying patients by
      decade to compare epidemiological data and cardinal symptoms. RESULTS: In total
      3674 patients with BD were reviewed. Significant proportional declines occurred
      with respect to male sex, complete type BD and major presenting features (genital
      ulcers, ocular involvement and skin lesions), whereas the mean patient age rose
      progressively, as did the frequencies of joint, gastrointestinal and central
      nervous system manifestations (all P < 0.0001). CONCLUSIONS: During the past
      three decades, clinical expression of BD in Korea has changed, resulting in fewer
      instances of complete type disease, declining male propensity, and shifting
      patterns of organ involvement.

PMID- 24117363
TI  - Three-dimensional moment arms and architecture of chimpanzee (Pan troglodytes)
      leg musculature.
AB  - The muscular and skeletal morphology of the chimpanzee ankle and foot differs
      from that of humans in many important respects. However, little information is
      available on the moment arms and architecture of the muscles that function around
      chimpanzee ankle and foot joints. The main goals of this study were to determine
      the influence of changes in leg and foot position on the moment arms of these
      muscle-tendon units (MTUs), and provide new measurements of their architecture.
      Three-dimensional moment arm data were collected from two adult, cadaveric Pan
      troglodytes specimens for 11 MTUs that cross the ankle and foot joints. Tendon
      excursion measurements were made throughout the full range of plantarflexion
      dorsiflexion (PF-DF) and eversion-inversion (EV-IN), including repeated
      measurements for mm. gastrocnemius at 0  degrees , 45  degrees , 90  degrees  and
      135  degrees  of knee flexion. The total range of motion was calculated from
      three-dimensional joint motion data while ensuring that foot movement was
      restricted to a single plane. Measurements of muscle mass, fascicle length,
      pennation angle and physiological cross-sectional area were then collected for
      each MTU. Our results demonstrate that joint position has a significant effect on
      moment arm lengths, and that in some cases this effect is counterintuitive. These
      new data contribute to filling a significant gap in previously published
      chimpanzee moment arm data, providing a comprehensive characterization of the
      MTUs that move the chimpanzee ankle and foot joints. They also provide empirical
      support to the notion that chimpanzees have larger ranges of motion at these
      joints than humans. Comparison of osteometric estimates of moment arm lengths to
      direct tendon-excursion measures provides some guidance for the use of skeletal
      features in estimations of PF-DF moment arms. Finally, muscle architecture data
      are consistent with the findings of previous studies, and increase the sample
      size of the chimpanzee data that are currently available. 

PMID- 24117365
TI  - A common novel splice variant of SLC22A1 (OCT1) is associated with impaired
      responses to imatinib in patients with chronic myeloid leukaemia.
AB  - Approximately one-third of patients with chronic myeloid leukaemia will fail to
      achieve or maintain responses to imatinib. Changes in solute carrier family 22
      (organic cation transporter), member 1 (SLC22A1, also termed OCT1), the main
      transporter for imatinib, have been proposed as a possible predictive factor. We
      analysed SLC22A1 mRNA levels and single nucleotide polymorphisms (SNPs) located
      in exon 7 in 153 diagnostic whole blood samples from two patient cohorts. The
      level of SLC22A1 expression did not significantly correlate with imatinib failure
      or achievement of molecular remission. The SNP 408V>M (g.1222G>A) was present in
      65% of patients and was associated in all cases with an eight base-pair insertion
      (8(+) allele) at the 3' end of exon 7. The latter generates an alternative splice
      site, leading to a premature stop codon. M420del was found in 33% of patients and
      never in cis with 8(+) (the 3(-) allele). Significantly longer times to 1% and
      0.1% molecular responses (by quantitative reverse transcription polymerase chain
      reaction) were seen in patients with 8(+) 8(+) or 8(+) N compared to those with
      the remaining four genotypes (N = no insertion or deletion). Patients lacking
      8(+) and 3(-) (NN, 18%) showed the best outcomes overall. Thus, while SLC22A1
      expression does not appear to affect response, alterations in its splicing or
      amino acid sequence may do so. 

PMID- 24117364
TI  - Properties of gene knockdown system by vector-based siRNA in zebrafish.
AB  - RNA interference (RNAi) has emerged as a powerful tool to silence specific genes.
      Vector-based RNAi systems have been developed to downregulate targeted genes in a
      spatially and temporally regulated fashion both in vitro and in vivo. The
      zebrafish (Danio rerio) is a model animal that has been examined based on a wide
      variety of biological techniques, including embryonic manipulations, forward and
      reverse genetics, and molecular biology. However, a heritable and tissue-specific
      knockdown of gene expression has not yet been developed in zebrafish. We examined
      two types of vector, which produce small interfering RNA (siRNA), the direct
      effector in RNAi system; microRNA (miRNA) process mimicking vectors with a
      promoter for RNA polymerase II and short hairpin RNA (shRNA) expressing vector
      through a promoter for RNA polymerase III. Though gene-silencing phenotypes were
      not observed in the miRNA process mimicking vectors, the transgenic embryos of
      the second vector (Tg(zU6-shGFP)), shRNA expressing vector for enhanced green
      fluorescence protein, revealed knockdown of the targeted gene. Interestingly,
      only the embryos from Tg(zU6-shGFP) female but not from the male fish showed the
      downregulation. Comparison of the quantity of siRNA produced by each vector
      indicates that the vectors tested here induced siRNA, but at low levels barely
      sufficient to silence the targeted gene. 

PMID- 24117367
TI  - Does the implementation of hardware need software? A longitudinal study on
      fluoride-removal filter use in Ethiopia.
AB  - Evidence suggests that the effectiveness of technology designed to provide safe
      and healthy water is dependent on the degree of its use. In addition to providing
      safe water "hardware" (i.e., new infrastructure or equipment) to populations at
      risk, it might be necessary to also provide suitable "software" programs
      (behavior change strategies) to support use. A longitudinal survey was conducted
      in rural Ethiopia following the distribution of fluoride-removal household
      filters. Three intervention groups were evaluated. Group 1 only received the
      hardware, i.e., the fluoride-removal filter. Groups 2 and 3 also received
      software in the form of two evidence-based psychological interventions: a
      planning and social prompts intervention and an educational workshop with
      pledging. Group 2 received both software interventions, and Group 3 only received
      the educational workshop. The effects of the hardware and software on behavior
      and thus filter use were analyzed along with specific psychological factors. The
      results showed that the provision of the hardware alone (the fluoride-removal
      filter) was not enough to ensure sufficient use of the equipment. The addition of
      a software component in the form of psychological interventions increased filter
      use up to 80%. An increase in filter use was measured following each intervention
      resulting in the health-risk being minimized. We conclude that it is necessary
      that the implementation of hardware of this nature is accompanied by evidence
      based intervention software. 

PMID- 24117366
TI  - Adiponectin and p53 mRNA in epicardial and subcutaneous fat from heart failure
      patients.
AB  - OBJECTIVE: Heart failure (HF) is associated with a pro-inflammatory state in
      epicardial fat, but the involved mechanisms are not entirely clear. The aim of
      our study was to assess the relationship between p53 and adiponectin mRNA in
      epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients
      with heart failure and its sympathetic regulation. METHODS: Epicardial adipose
      tissue and SAT samples were obtained from 63 patients undergoing elective cardiac
      surgery. EAT and SAT explants culture from seven patients were stimulated with
      isoprenaline 0.1 or 1 uM for 6 h. p53 and adiponectin mRNA expression was
      measured in frozen biopsies or explants culture from both fat pads by real-time
      polymerase chain reaction (PCR). RESULTS: We observed that EAT expressed more p53
      mRNA than SAT (1.73 +/- 0.07 vs. 1.69 +/- 0.04, P < 0.001) and its levels were
      higher in HF patients (1.75 +/- 0.07 vs. 1.70 +/- 0.04, P < 0.01 in EAT and 1.70
      +/- 0.04 vs. 1.67 +/- 0.04, P < 0.05 in SAT). Moreover, p53 mRNA expression was
      negatively correlated with adiponectin in EAT. After analysing the p53 mRNA
      regulation by isoprenaline, we observed that only EAT p53 expression increased
      after adrenergic stimulation (1.63 +/- 0.01 vs. 1.66 +/- 0.02; P = 0.024).
      CONCLUSIONS: p53 mRNA expression levels, inversely correlated with adiponectin,
      increase in EAT of HF patients and can be regulated by sympathetic activation
      pathway. Our findings can help to explain the deleterious effect of sympathetic
      activation in HF.

PMID- 24117368
TI  - Bimodal immune activation in psoriasis.
AB  - Psoriasis is an immune-regulated skin disease with various clinical subtypes and
      disease activities. The majority of patients present with predominantly stable
      plaques. At the onset of new lesions, plaque-type psoriasis frequently
      demonstrates pin-sized and highly inflammatory papules sometimes with an
      inflammatory border. The histopathology of initial psoriasis differs from stable
      plaque-type psoriasis. Early lesions demonstrate innate immune cells with
      neutrophils, degranulating mast cells and macrophages. These are followed by
      interleukin (IL)-1-dependent T helper (Th)17 cells, finally resulting in the Th1
      dominated immunopathology of stable plaque-type psoriasis, where mononuclear
      cells predominate with interspersed neutrophilic (Munro) microabscesses. These
      features suggest a bimodal immune pathway where alternate activation of either
      innate (autoinflammatory) or adaptive (autoimmune) immunity predominates.
      Neutrophilic infiltrations appear during early psoriasis with Munro abscesses.
      They are time limited and occur periodically, clinically best seen in linear nail
      pitting. These features strongly suggest a critical role for an IL-1-Th17
      dominated autoinflammation in the initiation of psoriasis, followed by a Th1
      dominated late-phase reaction. The concept of bimodal immune activation helps to
      explain results from therapeutic interventions that are variable and previously
      only partly understood. 

PMID- 24117369
TI  - Factors causing compositional changes in soy protein hydrolysates and effects on
      cell culture functionality.
AB  - Soy protein hydrolysates significantly enhance cell growth and recombinant
      protein production in cell cultures. The extent of this enhancement in cell
      growth and IgG production is known to vary from batch to batch. This can be due
      to differences in the abundance of different classes of compounds (e.g., peptide
      content), the quality of these compounds (e.g., glycated peptides), or the
      presence of specific compounds (e.g., furosine). These quantitative and
      qualitative differences between batches of hydrolysates result from variation in
      the seed composition and seed/meal processing. Although a considerable amount of
      literature is available that describes these factors, this knowledge has not been
      combined in an overview yet. The aim of this review is to identify the most
      dominant factors that affect hydrolysate composition and functionality. Although
      there is a limited influence of variation in the seed composition, the overview
      shows that the qualitative changes in hydrolysate composition result in the
      formation of minor compounds (e.g., Maillard reaction products). In pure systems,
      these compounds have a profound effect on the cell culture functionality. This
      suggests that the presence of these compounds in soy protein hydrolysates may
      affect hydrolysate functionality as well. This influence on the functionality can
      be of direct or indirect nature. For instance, some minor compounds (e.g.,
      Maillard reaction products) are cytotoxic, whereas other compounds (e.g.,
      phytates) suppress protein hydrolysis during hydrolysate production, resulting in
      altered peptide composition, and, thus, affect the functionality. 

PMID- 24117370
TI  - Reduced harm or another gateway to smoking? source, message, and information
      characteristics of E-cigarette videos on YouTube.
AB  - E-cigarettes are widely promoted on the Internet, but little is known about what
      kinds of information about them are available online. This study examines
      message, source, and health information characteristics of e-cigarette videos on
      the popular online video-sharing platform YouTube. A content analysis of 365 e
      cigarette videos indicates that 85% of the videos were sponsored by marketers.
      These videos highlight e-cigarettes' economic and social benefits, featuring a
      low level of fear appeal and negative message valence and a high level of
      marketing information about e-cigarette products. They also convey certain health
      claims that have been proscribed by the U.S. Food and Drug Administration, the
      prevalence of which warrants ongoing monitoring and regulatory guidelines for
      online e-cigarette marketing. 

PMID- 24117372
TI  - N-Heteropolycyclic compounds from the formal intramolecular (4 + 1)-cycloaddition
      of chromium aminocarbenes.
AB  - Chromium aminocarbenes tethered to dienes of all three electronic natures undergo
      an efficient intramolecular (4 + 1)-cycloaddition to give N-heteropolycyclic
      compounds. Ligands on chromium had a profound effect on the course of the
      reaction. 

PMID- 24117371
TI  - Breast cancer screening, area deprivation, and later-stage breast cancer in
      Appalachia: does geography matter?
AB  - OBJECTIVE: To model the relationship of an area-based measure of a breast cancer
      screening and geographic area deprivation on the incidence of later stage breast
      cancer (LSBC) across a diverse region of Appalachia. DATA SOURCE: Central cancer
      registry data (2006-2008) from three Appalachian states were linked to Medicare
      claims and census data. STUDY DESIGN: Exploratory spatial analysis preceded the
      statistical model based on negative binomial regression to model predictors and
      effect modification by geographic subregions. PRINCIPAL FINDINGS: Exploratory
      spatial analysis revealed geographically varying effects of area deprivation and
      screening on LSBC. In the negative binomial regression model, predictors of LSBC
      included receipt of screening, area deprivation, supply of mammography centers,
      and female population aged>75 years. The most deprived counties had a 3.31 times
      greater rate of LSBC compared to the least deprived. Effect of screening on LSBC
      was significantly stronger in northern Appalachia than elsewhere in the study
      region, found mostly for high-population counties. CONCLUSIONS: Breast cancer
      screening and area deprivation are strongly associated with disparity in LBSC in
      Appalachia. The presence of geographically varying predictors of later stage
      tumors in Appalachia suggests the importance of place-based health care access
      and risk.

PMID- 24117373
TI  - Frequency-dependent relationship between resting-state functional magnetic
      resonance imaging signal power and head motion is localized within distributed
      association networks.
AB  - Recent studies have highlighted the importance of analyzing spectral power in
      resting-state functional magnetic resonance imaging (rs-fMRI) data. Significant
      modulation of power has been ascribed to the performance of cognitive tasks and
      has been ascribed clinical significance. However, the role of confounding factors
      such as head motion on spectral power is not fully understood. Specifically, the
      spatial distribution of frequency-dependent associations between rs-fMRI power
      and motion is unknown. We utilized a large rs-fMRI dataset (n=1000) to quantify
      the influence of head motion on spectral power in different frequency bands. We
      (1) performed regression analyses across the entire sample and (2) computed
      difference maps between high- and low-motion groups, more consistent with common
      experimental designs, and both analyses gave similar results. Greater head motion
      led to reduced spectral power at lower frequencies (0.007-0.05 Hz), but increased
      power at higher frequencies (0.12-0.167 Hz). Importantly, our whole-brain voxel
      wise analysis showed that brain areas in distributed association networks (e.g.,
      default mode and frontoparietal control networks) were most susceptible to head
      motion. These results were consistent with or without global signal regression
      (GSR). Additionally, without GSR, we noted a positive correlation with low
      frequency power in the pre- and postcentral gyrus (S1/M1), mid-cingulate cortex,
      and insula and a negative correlation with mid-frequency (0.05-0.12 Hz) power in
      S1/M1, visual, and lateral temporal cortices. Hence, head motion significantly
      affects rs-fMRI power and great care must be taken when assigning a diagnostic
      marker for clinical populations known to present with greater head motion.

PMID- 24117374
TI  - Tea consumption and mortality in the oldest-old Chinese.
AB  - OBJECTIVES: To investigate the association between tea consumption and mortality
      in the oldest-old Chinese. DESIGN: Population-based longitudinal data from the
      Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed using a Cox
      semiparametric proportional hazard model. SETTING: Six hundred thirty-one
      randomly selected counties and cities of China's 22 provinces. PARTICIPANTS:
      Individuals aged 80 and older (N = 9,093) who provided complete data in the
      baseline survey (1998). MEASUREMENTS: Self-reported current frequency of tea
      drinking and past frequency at approximately age 60 were ascertained at baseline
      survey; a follow-up survey was conducted 2000, 2002, and 2005. RESULTS: In the
      oldest-old Chinese, tea consumption was associated with lower risk of mortality
      after adjusting for demographic characteristics, socioeconomic status, health
      practices, and health status. Compared with non-tea drinkers, the adjusted hazard
      ratio (HR) was 0.90 (95% confidence interval (CI) = 0.84-0.96) for daily tea
      drinkers (at the baseline survey, 1998) and 1.00 (95% CI = 1.01-1.07) for
      occasional tea drinkers (P for linear trend .003). Similar results were found
      when tea drinking status at age 60 was used in the analysis. Further analysis
      showed that subjects who reported frequent tea drinking at age 60 and at the
      baseline survey had a 10% lower risk of mortality than subjects who reported
      infrequent tea drinking at age 60 and at the baseline survey (HR = 0.90, 95% CI =
      0.84-0.97). CONCLUSION: Tea consumption is associated with lower risk of
      mortality in the oldest-old Chinese.

PMID- 24117375
TI  - Breakdown of dioecy: models where males acquire cosexual functions.
AB  - We have reanalyzed models of the breakdown of dioecy involving modified males to
      investigate female frequencies in the resulting gynodioecious populations. We
      extend and simplify previous treatments to deal with biologically relevant
      factors including pollen limitation, partial selfing of modified males, and
      inbreeding depression, to highlight the different empirically detectable
      advantages that may be gained by modified males that can reproduce as cosexes
      (i.e., can produce some seeds); these include "inconstant males," which can
      sometimes display some female function. Males reproducing wholly or occasionally
      as cosexual phenotypes can gain the transmission advantage of selfing, if partial
      self-fertilization is possible, and from reproductive assurance when pollen is
      limiting. If, because of resource limitation, such cosexual phenotypes produce
      fewer ovules than females, their nonselfed ovules will require a lower pollen
      pool size for full seed-set, compared with females. We investigate the conditions
      for these benefits to allow modified males to invade dioecious populations.
      Sometimes, such invasion leads to replacement of dioecy by the cosexual type, but
      sometimes the breakdown populations remain sexually polymorphic. When competition
      occurs between genotypes in the pollen load on a flower, high female frequencies
      can arise when Y chromosome-bearing pollen competes poorly with X pollen. 

PMID- 24117376
TI  - Selective protein immobilization onto gold nanoparticles deposited under vacuum
      on a protein-repellent self-assembled monolayer.
AB  - The immobilization of proteins on flat substrates plays an important role for a
      wide spectrum of applications in the fields of biology, medicine, and
      biochemistry, among others. An essential prerequisite for the use of proteins
      (e.g., in biosensors) is the conservation of their biological activity. Losses in
      activity upon protein immobilization can largely be attributed to a random
      attachment of the proteins to the surface. In this study, we present an approach
      for the immobilization of proteins onto a chemically heterogeneous surface,
      namely a surface consisting of protein-permissive and protein-repellent areas,
      which allows for significant reduction of random protein attachment. As protein
      permissive, i.e., as protein-binding sites, ultra pure metallic nanoparticles are
      deposited under vacuum onto a protein-repellent PEG-silane polymer layer. Using
      complementary surface characterization techniques (atomic force microscopy,
      quartz crystal microbalance, and X-ray photoelectron spectroscopy) we demonstrate
      that the Au nanoparticles remain accessible for protein attachment without
      compromising the protein-repellency of the PEG-silane background. Moreover, we
      show that the amount of immobilized protein can be controlled by tuning the Au
      nanoparticle coverage. This method shows potential for applications requiring the
      control of protein immobilization down to the single molecule level. 

PMID- 24117377
TI  - Cytochrome P450 modified polycrystalline indium tin oxide film as a drug
      metabolizing electrochemical biosensor with a simple configuration.
AB  - The development of a biocatalytic electrode consisting of cytochrome P450 (CYP)
      proteins would be a key technology with which to establish simple drug
      metabolizing biosensors or screening devices for drug inhibitors. We have
      successfully detected the direct electron transfer (DET) from a human CYP layer
      or a CYP microsome adsorbed on a bare indium tin oxide (ITO) film electrode
      without any modification layers and applied it to drug metabolism evaluation. We
      compared the electrocatalytic properties of the two ITO films with different
      surface nanostructures (polycrystalline or amorphous). CYP on polycrystalline ITO
      film enhanced the electron transfer rate of oxygen reduction about fifteen times
      more than with amorphous film. The polycrystalline ITO film was a suitable
      electrode for the adsorption of CYP proteins while maintaining efficient DET and
      enzymatic activity, probably because of its larger surface area and negatively
      charged surface. The oxygen reduction current at the polycrystalline ITO film
      electrodes had increased 3- to 4-fold, specifically coupled with the oxidation of
      drugs (testosterone and quinidine) by the monooxygenase activity of CYP. In
      contrast, the oxygen reduction current completely disappeared in the presence of
      the CYP inhibitor (ketoconazole). Similar results could be obtained from the CYP
      microsome with sufficiently clear responses. These results indicate that the CYP
      modified polycrystalline ITO electrode offers the potential for electrochemically
      evaluating CYP activity for drug metabolism with a simple configuration. 

PMID- 24117379
TI  - Epilepsia editorial: publications by country.

PMID- 24117378
TI  - Unbiased screening of marine sponge extracts for anti-inflammatory agents
      combined with chemical genomics identifies girolline as an inhibitor of protein
      synthesis.
AB  - Toll-like receptors (TLRs) play a critical role in innate immunity, but
      activation of TLR signaling pathways is also associated with many harmful
      inflammatory diseases. Identification of novel anti-inflammatory molecules
      targeting TLR signaling pathways is central to the development of new treatment
      approaches for acute and chronic inflammation. We performed high-throughput
      screening from crude marine sponge extracts on TLR5 signaling and identified
      girolline. We demonstrated that girolline inhibits signaling through both MyD88
      dependent and -independent TLRs (i.e., TLR2, 3, 4, 5, and 7) and reduces cytokine
      (IL-6 and IL-8) production in human peripheral blood mononuclear cells and
      macrophages. Using a chemical genomics approach, we identified Elongation Factor
      2 as the molecular target of girolline, which inhibits protein synthesis at the
      elongation step. Together these data identify the sponge natural product
      girolline as a potential anti-inflammatory agent acting through inhibition of
      protein synthesis. 

PMID- 24117380
TI  - Hypoxia modulates the activity of a series of clinically approved tyrosine kinase
      inhibitors.
AB  - BACKGROUND AND PURPOSE: Hypoxia in tumours is known to cause resistance to
      conventional chemotherapeutic drugs. In contrast, little is known about the
      effects of hypoxia on targeted anti-cancer drugs. This study evaluated the effect
      of hypoxia on a series of clinically approved tyrosine kinase inhibitors (TKIs).
      EXPERIMENTAL APPROACH: The effect of hypoxia (0.1% oxygen) on the activity of
      conventional cytotoxic drugs (5-fluorouracil, doxorubicin and vinblastine), the
      hypoxia-activated prodrug tirapazamine and 9 TKIs was determined in a panel of
      cell lines. Where hypoxia had a marked effect on chemosensitivity, Western blot
      analysis was conducted to determine the effect of hypoxia on target expression
      and the effect of TKIs on cell signalling response under aerobic and hypoxic
      conditions. KEY RESULTS: Three patterns of chemosensitivity were observed:
      resistance under hypoxia, equitoxic activity against hypoxic and aerobic cells,
      and preferential cytotoxicity to hypoxic cells. Significant hypoxia selectivity
      (independent of HIF1) was observed in the case of dasatinib and this correlated
      with the ability of dasatinib to inhibit phosphorylation of Src at tyrosine 530.
      Sorafenib was significantly less effective under hypoxic conditions but
      resistance did not correlate with hypoxia-induced changes in Raf/MEK/ERK
      signalling. CONCLUSIONS AND IMPLICATIONS: Hypoxia influences the activity of TKIs
      but in contrast to conventional cytotoxic drugs, preferential activity against
      hypoxic cells can occur. The search for hypoxia-targeted therapies has been long
      and fruitless and this study suggests that some clinically approved TKIs could
      preferentially target the hypoxic fraction of some tumour types.

PMID- 24117382
TI  - Stability of cerebral metabolism and substrate availability in humans during
      hypoxia and hyperoxia.
AB  - Characterization of the influence of oxygen availability on brain metabolism is
      an essential step toward a better understanding of brain energy homoeostasis and
      has obvious clinical implications. However, how brain metabolism depends on
      oxygen availability has not been clearly examined in humans. We therefore
      assessed the influence of oxygen on CBF (cerebral blood flow) and CMRO2 (cerebral
      metabolic rates for oxygen) and carbohydrates. PaO2 (arterial partial pressure of
      oxygen) was decreased for 15 min to ~60, ~44 and ~35 mmHg [to target a SaO2
      (arterial oxygen saturation) of 90, 80 and 70% respectively], and elevated to
      ~320 and ~430 mmHg. Isocapnia was maintained during each trial. At the end of
      each stage, arterial-jugular venous differences and volumetric CBF were measured
      to directly calculate cerebral metabolic rates. During progressive hypoxaemia,
      elevations in CBF were correlated with the reductions in both SaO2 (R2=0.54,
      P<0.05) and CaO2 (arterial oxygen content) (R2=0.57, P<0.05). Despite markedly
      reduced CaO2, cerebral oxygen delivery was maintained by increased CBF. Cerebral
      metabolic rates for oxygen, glucose and lactate remained unaltered during
      progressive hypoxia. Consequently, cerebral glucose delivery was in excess of
      that required, and net lactate efflux increased slightly in severe hypoxia, as
      reflected by a small increase in jugular venous lactate. Progressive hyperoxia
      did not alter CBF, CaO2, substrate delivery or cerebral metabolism. In
      conclusion, marked elevations in CBF with progressive hypoxaemia and related
      reductions in CaO2 resulted in a well-maintained cerebral oxygen delivery. As
      such, cerebral metabolism is still supported almost exclusively by carbohydrate
      oxidation during severe levels of hypoxaemia. 

PMID- 24117383
TI  - Dermatoses secondary to Indian cultural practices.

PMID- 24117381
TI  - Delayed onset of bilateral acute retinal necrosis syndrome: a 46-year interval.
AB  - BACKGROUND: Acute retinal necrosis (ARN) syndrome is an uncommon, severe form of
      retinitis that is caused by the herpes virus family. Bilateral acute retinal
      necrosis (BARN) at delayed onset is rare. METHODS: A retrospective,
      interventional case is described in a 64-year-old man complaining of blurred
      vision in the left eye. The patient had a history of presumed ARN in the right
      eye at the age of 18 years. RESULTS: The reduced visual acuity and the ocular
      fundus signs lead us to the diagnosis of delayed-onset BARN. Intravenous and
      intravitreal antiviral therapy, corticosteroid and antiplatelet treatment were
      administered until recovering final visual acuity. CONCLUSIONS: This report
      represents the longest reported interval of ARN quiescence with eventual
      bilateral involvement and illustrates the importance of long-term patient follow
      up in immunocompetent patients.

PMID- 24117384
TI  - Dispersal in a patchy landscape reveals contrasting determinants of infection in
      a wild avian malaria system.
AB  - Understanding exactly when, where and how hosts become infected with parasites is
      critical to understanding host-parasite co-evolution in natural populations.
      However, for host-parasite systems in which hosts or parasites are mobile, for
      example in vector-borne diseases, the spatial location of infection and the
      relative importance of parasite exposure at successive host life-history stages
      are often uncertain. Here, using a 6-year longitudinal data set from a spatially
      referenced population of blue tits, we test the extent to which infection by
      avian malaria parasites is determined by conditions experienced at natal or
      breeding sites, as well as by postnatal dispersal between the two. We show that
      the location and timing of infection differs markedly between two sympatric
      malaria parasite species. For one species (Plasmodium circumflexum), our analyses
      indicate that infection occurs after birds have settled on breeding territories,
      and because the distribution of this parasite is temporally stable across years,
      hosts born in malarious areas could in principle alter their exposure and
      potentially avoid infection through postnatal dispersal. Conversely, the spatial
      distribution of another parasite species (Plasmodium relictum) is unpredictable
      and infection probability is positively associated with postnatal dispersal
      distance, potentially indicating that infection occurs during this major
      dispersal event. These findings suggest that hosts in this population may be
      subject to divergent selection pressures from these two parasites, potentially
      acting at different life-history stages. Because this implies parasite species
      specific predictions for many coevolutionary processes, they also illustrate the
      complexity of predicting such processes in multi-parasite systems.

PMID- 24117385
TI  - Ring-closing reaction in diarylethene captured by femtosecond electron
      crystallography.
AB  - The photoinduced ring-closing reaction in diarylethene, which serves as a model
      system for understanding reactive crossings through conical intersections, was
      directly observed with atomic resolution using femtosecond electron diffraction.
      Complementary ab initio calculations were also performed. Immediately following
      photoexcitation, subpicosecond structural changes associated with the formation
      of an open-ring excited-state intermediate were resolved. The key motion is the
      rotation of the thiophene rings, which significantly decreases the distance
      between the reactive carbon atoms prior to ring closing. Subsequently, on the few
      picosecond time scale, localized torsional motions of the carbon atoms lead to
      the formation of the closed-ring photoproduct. These direct observations of the
      molecular motions driving an organic chemical reaction were only made possible
      through the development of an ultrabright electron source to capture the atomic
      motions within the limited number of sampling frames and the low data acquisition
      rate dictated by the intrinsically poor thermal conductivity and limited
      photoreversibility of organic materials. 

PMID- 24117387
TI  - Unintended environmental consequences and co-benefits of economic restructuring.
AB  - Current economic restructuring policies have ignored unintended environmental
      consequences and cobenefits, the understanding of which can provide foundations
      for effective policy decisions for green economy transformation. Using the input
      output life cycle assessment model and taking China as an example, we find that
      household consumption, fixed capital formation, and export are main drivers to
      China's environmental impacts. At the product scale, major contributors to
      environmental impacts vary across different types of impacts. Stimulating the
      development of seven strategic emerging industries will cause unintended
      consequences, such as increasing nonferrous metal ore usage, terrestrial
      acidification, photochemical oxidant formation, human toxicity, and terrestrial
      ecotoxicity. Limiting the surplus outputs in the construction materials industry
      and metallurgy industry may only help mitigate some of the environmental impacts
      caused by China's regulated pollutants, with little effect on reducing other
      impacts, such as marine eutrophication, terrestrial acidification, photochemical
      oxidant formation, and particulate matter formation. However, it will bring
      cobenefits by simultaneously reducing mineral ore usage, human toxicity, marine
      ecotoxicity, and terrestrial ecotoxicity. Sustainable materials management and
      integrated policy modeling are possible ways for policy-making to avoid
      unintended consequences and effectively utilize cobenefits. 

PMID- 24117386
TI  - Immunolocalisation of fibrillin microfibrils in the calf metacarpal and vertebral
      growth plate.
AB  - Overgrowth of limbs and spinal deformities are typical clinical manifestations of
      Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA), caused by
      mutations of the genes encoding fibrillin-1 (FBN1) and fibrillin-2 (FBN2),
      respectively. FBN1 mutations are also associated with acromicric (AD) and
      geleophysic dysplasias (GD), and with Weill-Marchesani syndrome (WMS), which is
      characterised by short stature. The mechanisms leading to such abnormal skeletal
      growth and the involvement of the fibrillins are not understood. Postnatal
      longitudinal bone growth mainly occurs in the epiphyseal growth plate. Here we
      investigated the organisation of fibrillin microfibrils in the growth plate of
      the long bone and vertebra immunohistochemically. Fibrillin-1 was dual
      immunostained with elastin, with fibrillin-2 or with collagen X. We report that
      fibrillin microfibrils are distributed throughout all regions of the growth
      plate, and that fibrillin-1 and fibrillin-2 were differentially organised.
      Fibrillin-1 was more abundant in the extracellular matrix of the resting and
      proliferative zones of the growth plate than in the hypertrophic zone. More
      fibrillin-2 was found in the calcified region than in the other regions. No
      elastin fibres were observed in either the proliferative or hypertrophic zones.
      This study indicates that, as fibrillin microfibrils are involved in growth
      factor binding and may play a mechanical role, they could be directly involved in
      regulating bone growth. Hence, mutations of the fibrillins could affect their
      functional role in growth and lead to the growth disorders seen in patients with
      MFS, CCA, AD, GD and WMS. 

PMID- 24117388
TI  - A connectionist approach to mapping the human connectome permits simulations of
      neural activity within an artificial brain.
AB  - Data-driven models drawn from statistical correlations between brain activity and
      behavior are used to inform theory-driven models, such as those described by
      computational models, which provide a mechanistic account of these correlations.
      This article introduces a novel multivariate approach for bootstrapping
      neurologically-plausible computational models that accurately encodes cortical
      effective connectivity from resting state functional neuroimaging data (rs-fMRI).
      We show that a network modularity algorithm finds comparable resting state
      networks within connectivity matrices produced by our approach and by the
      benchmark method. Unlike existing methods, however, ours permits simulation of
      brain activation that is a direct reflection of this cortical connectivity. Cross
      validation of our model suggests that neural activity in some regions may be more
      consistent between individuals, providing novel insight into brain function. We
      suggest this method to make an important contribution toward modeling macro-scale
      human brain activity, and it has the potential to advance our understanding of
      complex neurological disorders and the development of neural connectivity.

PMID- 24117389
TI  - Ustekinumab improves nail disease in patients with moderate-to-severe psoriasis:
      results from PHOENIX 1.
AB  - BACKGROUND: Most patients with psoriasis have nail changes, and treating nail
      psoriasis is challenging. OBJECTIVES: To assess improvement in fingernail
      psoriasis with ustekinumab treatment in the PHOENIX 1 trial. METHODS: Patients
      received ustekinumab 45 mg or 90 mg, or placebo at weeks 0 and 4. Ustekinumab
      randomized patients continued maintenance dosing every 12 weeks, while patients
      receiving placebo crossed over to receive ustekinumab 45 mg or 90 mg at weeks
      12/16 followed by dosing every 12 weeks. At week 40, initial responders [those
      with >= 75% improvement from baseline in Psoriasis Area and Severity Index (PASI
      75)] were rerandomized either to continue maintenance dosing or to withdraw from
      treatment. Nail involvement was evaluated using the Nail Psoriasis Severity Index
      (NAPSI) on a target fingernail, Nail Physician's Global Assessment (Nail PGA) and
      mean number of nails involved. RESULTS: Of 766 randomized patients, 545 (71.1%)
      had nail psoriasis. At week 24, the percentage improvement from baseline NAPSI
      score was 46.5% (ustekinumab 45 mg) and 48.7% (ustekinumab 90 mg). Percentage
      improvements in NAPSI ranged from 29.7% (PASI < 50) to 57.3% (PASI >= 90). Mean
      NAPSI scores improved from 4.5 at baseline to 2.4 at week 24 (45 mg) and from 4.4
      to 2.2 (90 mg). Nail PGA scores and the mean number of psoriatic nails improved
      by week 24. Further improvement was observed for all end points among initial
      responders continuing maintenance treatment through week 52. CONCLUSIONS:
      Ustekinumab significantly improves nail psoriasis, and improvements continue over
      time until up to 1 year of treatment in those receiving maintenance treatment.

PMID- 24117390
TI  - Trust during the early stages of the 2009 H1N1 pandemic.
AB  - Distrust of the government often stands in the way of cooperation with public
      health recommendations in a crisis. The purpose of this article is to describe
      the public's trust in government recommendations during the early stages of the
      H1N1 pandemic and to identify factors that might account for these trust levels.
      The authors surveyed 1,543 respondents about their experiences and attitudes
      related to H1N1 influenza between June 3, 2009, and July 6, 2009, during the
      first wave of the pandemic using the Knowledge Networks online panel. This panel
      is representative of the U.S. population and uses a combination of random digit
      dialing and address-based probability sampling frames covering 99% of the U.S.
      household population to recruit participants. To ensure participation of low
      income individuals and those without Internet access, Knowledge Networks provides
      hardware and access to the Internet if needed. Measures included standard
      demographics, a trust scale, trust ratings for individual spokespersons,
      involvement with H1N1, experience with H1N1, and past discrimination in health
      care. The authors found that trust of government was low (2.3 out of 4) and
      varied across demographic groups. Blacks and Hispanics reported higher trust in
      government than did Whites. Of the spokespersons included, personal health
      professionals received the highest trust ratings and religious leaders the
      lowest. Attitudinal and experience variables predicted trust better than
      demographic characteristics. Closely following the news about the flu virus,
      having some self-reported knowledge about H1N1, self-reporting of local cases,
      and previously experiencing discrimination were the significant attitudinal and
      experience predictors of trust. Using a second longitudinal survey, trust in the
      early stages of the pandemic predicted vaccine acceptance later but only for
      White, non-Hispanic individuals. 

PMID- 24117392
TI  - Dynamic enhancement in adhesion forces of microparticles on substrates.
AB  - We report a dynamically induced enhancement in interfacial adhesion between
      microsized particles and substrates under dry and humid conditions. The adhesion
      force of soft (polystyrene) and hard (SiO2 and Al2O3) microparticles on soft
      (polystyrene) and hard (fused silica and sapphire) substrates was measured by
      using an atomic force microscope with retraction (z-piezo) speed ranging over 4
      orders of magnitude. The adhesion is strongly enhanced by the dynamic effect.
      When the retraction speed varies from 0.02 to 156 MUm/s, the adhesion force
      increases by 10% to 50% in dry nitrogen while it increases by 15% to 70% in humid
      air. Among the material systems tested, the soft-soft contact systems exhibit the
      smallest dynamic effect while the hard-hard contacts show the largest
      enhancement. A dynamic model was developed to predict this dynamic effect, which
      agrees well with the experimental results. The influence of dynamic factors
      related to the adhesion enhancement, such as particle inertia, viscoelastic
      deformations, and crack propagation, was discussed to understand the dynamic
      enhancement mechanisms. 

PMID- 24117391
TI  - Identification of small molecules inhibiting diguanylate cyclases to control
      bacterial biofilm development.
AB  - Biofilm formation by pathogenic bacteria is an important virulence factor in the
      development of numerous chronic infections, thereby causing a severe health
      burden. Many of these infections cannot be resolved, as bacteria in biofilms are
      resistant to the host's immune defenses and antibiotic therapy. An urgent need
      for new strategies to treat biofilm-based infections is critically needed. Cyclic
      di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential for
      biofilm formation. The absence of this signalling system in higher eukaryotes
      makes it an attractive target for the development of new anti-biofilm agents. In
      this study, the results of an in silico pharmacophore-based screen to identify
      small-molecule inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c
      di-GMP are described. Four small molecules, LP 3134, LP 3145, LP 4010 and LP 1062
      that antagonize these enzymes and inhibit biofilm formation by Pseudomonas
      aeruginosa and Acinetobacter baumannii in a continuous-flow system are reported.
      All four molecules dispersed P. aeruginosa biofilms and inhibited biofilm
      development on urinary catheters. One molecule dispersed A. baumannii biofilms.
      Two molecules displayed no toxic effects on eukaryotic cells. These molecules
      represent the first compounds identified from an in silico screen that are able
      to inhibit DGC activity to prevent biofilm formation. 

PMID- 24117393
TI  - Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA): development and
      validation of a tool for assessment of nail psoriasis outcomes.
AB  - BACKGROUND: Existing tools for nail psoriasis are complex and may not adequately
      measure outcomes that are important to patients. OBJECTIVES: We have developed
      and validated a new tool, the Nail Assessment in Psoriasis and Psoriatic
      Arthritis (NAPPA), with three components: a questionnaire assessing quality of
      life (NAPPA-QoL), a two-part questionnaire assessing patient-relevant treatment
      benefits (the Patient Benefit Index, NAPPA-PBI) and a psoriasis Clinical
      Assessment of Severity (NAPPA-CLIN). METHODS: Development of the questionnaires
      involved multiple steps: (i) collection of items about nail psoriasis-related
      impairments and treatment goals; (ii) selection of 48 items by an expert panel,
      including patients; (iii) translation into eight languages; (iv) feasibility
      testing and (v) longitudinal validation in six countries. RESULTS: Patients found
      the questionnaires clear (84%) and comprehensible (95%). NAPPA-QoL and NAPPA-PBI
      scores correlated moderately with clinical outcomes [e.g. Nail Psoriasis Severity
      Index (NAPSI)] and markedly with other quality-of-life questionnaires (e.g. EQ
      5DTM). Both questionnaires were sensitive to change. Internal consistency was
      good (Cronbach alpha >= 0.88 for all scales). The NAPPA-CLIN, a brief version of
      NAPSI that involves assessment of only four digits rather than all 20, was found
      to correlate highly with total NAPSI score (r = 0.97, P < 0.001). CONCLUSIONS:
      Overall, the three-component NAPPA tool is a valid, reliable and practical
      instrument to assess patient-relevant nail psoriasis outcomes.

PMID- 24117394
TI  - Improving adhesion of seasonings to crackers with hydrocolloid solutions.
AB  - Food powders were applied on crackers that had been coated using water, oil,
      emulsion, sucrose, or hydrocolloid solutions. The hydrocolloids that were used
      include gellan gum, kappa-carrageenan, methylcellulose, gum karaya, gum
      tragacanth, gum arabic, guar gum, modified starch, and maltodextrin. Solutions of
      similar hydrophobicity to the powder gave the greatest adhesion. NaCl, barbecue
      (BBQ), ranch, and sour cream & onion (SC&O) seasoning showed greatest adhesion
      with water, cheese powder with an emulsion of 12.5% to 25% oil, and cocoa powder
      with oil. For NaCl, BBQ, ranch, and SC&O seasoning, hydrocolloids improved the
      adhesion over using water alone, with gellan gum providing the greatest adhesion.
      Hydrocolloid structural differences, including the presence or absence of
      branching, substitution of sugar units, and molecular weight affect water binding
      and thickening of the hydrocolloid spray that seemed to be significant factors
      affecting adhesion of powders to the target surface. For cheese powder,
      hydrocolloids were capable of replacing the oil within an emulsion while
      improving or maintaining the same level of adhesion, with gum arabic providing
      the greatest adhesion. For cocoa powder, hydrocolloid solutions were ineffective
      adhesives due to differences in hydrophilicity that result in insolubility. The
      effect of hydrocolloid concentration on adhesion was dependent both on the
      hydrocolloid type and the concentration that is sprayable, with 0.5% being the
      optimum concentration for most gums. Adhesion using sucrose solutions was
      determined by particle size and relative hydrophobicity. Increasing sucrose
      concentration decreased adhesion of smaller particles, but increased adhesion of
      larger particles. Adhesion of NaCl significantly increased with decreasing NaCl
      size using oil, water, and sucrose solutions. 

PMID- 24117396
TI  - The significance of dyserythropoiesis.

PMID- 24117395
TI  - Copper-catalyzed decarboxylative trifluoromethylation of allylic
      bromodifluoroacetates.
AB  - The development of new synthetic fluorination reactions has important
      implications in medicinal, agricultural, and materials chemistries. Given the
      prevalence and accessibility of alcohols, methods to convert alcohols to
      trifluoromethanes are desirable. However, this transformation typically requires
      four-step processes, specialty chemicals, and/or stoichiometric metals to access
      the trifluoromethyl-containing product. A two-step copper-catalyzed
      decarboxylative protocol for converting allylic alcohols to trifluoromethanes is
      reported. Preliminary mechanistic studies distinguish this reaction from
      previously reported Cu-mediated reactions. 

PMID- 24117397
TI  - Development of a composite measure of state-level malpractice environment.
AB  - OBJECTIVE: To develop a composite measure of state-level malpractice environment.
      DATA SOURCES: Public use data from the National Practitioner Data Bank, Medical
      Liability Monitor, the National Conference of State Legislatures, and the
      American Bar Association. STUDY DESIGN: Principal component analysis of state
      level indicators (paid claims rate, malpractice premiums, lawyers per capita,
      average award size, and malpractice laws), with indirect validation of the
      composite using receiver-operating characteristic curves to determine how
      accurately the composite could identify states with high-tort activity and costs.
      PRINCIPAL FINDINGS: A single composite accounted for over 73 percent of total
      variance in the seven indicators and demonstrated reasonable criterion validity.
      CONCLUSION: An empirical composite measure of state-level malpractice risk may
      offer advantages over single indicators in measuring overall risk and may
      facilitate cross-state comparisons of malpractice environments.

PMID- 24117399
TI  - Why ontogeny matters during adaptation: developmental niche construction and
      pleiotorpy across the life cycle in Arabidopsis thaliana.
AB  - This case study of adaptation in Arabidopsis thaliana shows that natural
      selection on early life stages can be intense and can influence the evolution of
      subsequent traits. Two mechanisms contribute to this influence: pleiotropy across
      developmental stages and developmental niche construction. Examples are given of
      pleiotropy of environmentally cued development across life stages, and potential
      ways that pleiotropy can be relieved are discussed. In addition, this case study
      demonstrates how the timing of prior developmental transitions determines the
      seasonal environment experienced subsequently, and that such developmental niche
      construction alters phenotypic expression of subsequent traits, the expression of
      genetic variation of those traits, and natural selection on those traits and
      alleles associated with them. As such, developmental niche construction modifies
      pleiotropic relationships across the life cycle in ways that influence the
      dynamics of adaptation. Understanding the genetic basis of life-cycle variation
      therefore requires consideration of environmental effects on pleiotropy. 

PMID- 24117398
TI  - Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT(1A)
      receptors without diminishing nervous system function or chemotherapy efficacy.
AB  - BACKGROUND AND PURPOSE: Paclitaxel (PAC) is associated with chemotherapy-induced
      neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer
      patients even in the absence of alternate therapies. We previously reported that
      chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD)
      prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought
      to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD
      negatively effects nervous system function or chemotherapy efficacy. EXPERIMENTAL
      APPROACH: The ability of acute CBD pretreatment to prevent PAC-induced mechanical
      sensitivity was assessed, as was the effect of CBD on place conditioning and on
      an operant-conditioned learning and memory task. The potential interaction of CBD
      and PAC on breast cancer cell viability was determined using the MTT assay. KEY
      RESULTS: PAC-induced mechanical sensitivity was prevented by administration of
      CBD (2.5 - 10 mg.kg-1) in female C57Bl/6 mice. This effect was reversed by co
      administration of the 5-HT(1A) antagonist WAY 100635, but not the CB1 antagonist
      SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding
      effects and did not affect conditioned learning and memory. Also, CBD + PAC
      combinations produce additive to synergistic inhibition of breast cancer cell
      viability. CONCLUSIONS AND IMPLICATIONS: Our data suggest that CBD is protective
      against PAC-induced neurotoxicity mediated in part by the 5-HT(1A) receptor
      system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or
      cognitive impairment and did not attenuate PAC-induced inhibition of breast
      cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy
      may be safe and effective in the prevention or attenuation of CIPN.

PMID- 24117400
TI  - Structural basis of the promiscuous inhibitor susceptibility of Escherichia coli
      LpxC.
AB  - The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising
      and clinically unexploited antibiotic targets for treatment of multidrug
      resistant Gram-negative infections. Progress in medicinal chemistry has led to
      the discovery of potent LpxC inhibitors with a variety of chemical scaffolds and
      distinct antibiotic profiles. The vast majority of these compounds, including the
      nanomolar inhibitors L-161,240 and BB-78485, are highly effective in suppressing
      the activity of Escherichia coli LpxC (EcLpxC) but not divergent orthologs such
      as Pseudomonas aeruginosa LpxC (PaLpxC) in vitro. The molecular basis for such
      promiscuous inhibition of EcLpxC has remained poorly understood. Here, we report
      the crystal structure of EcLpxC bound to L-161,240, providing the first molecular
      insight into L-161,240 inhibition. Additionally, structural analysis of the
      EcLpxC/L-161,240 complex together with the EcLpxC/BB-78485 complex reveals an
      unexpected backbone flipping of the Insert I betaa-betab loop in EcLpxC in
      comparison with previously reported crystal structures of EcLpxC complexes with l
      threonyl-hydroxamate-based broad-spectrum inhibitors. Such a conformational
      switch, which has only been observed in EcLpxC but not in divergent orthologs
      such as PaLpxC, results in expansion of the active site of EcLpxC, enabling it to
      accommodate LpxC inhibitors with a variety of head groups, including compounds
      containing single (R- or S-enantiomers) or double substitutions at the
      neighboring Calpha atom of the hydroxamate warhead group. These results highlight
      the importance of understanding inherent conformational plasticity of target
      proteins in lead optimization. 

PMID- 24117401
TI  - Systems biology analysis of the endocannabinoid system reveals a scale-free
      network with distinct roles for anandamide and 2-arachidonoylglycerol.
AB  - We represented the endocannabinoid system (ECS) as a biological network, where
      ECS molecules are the nodes (123) and their interactions the links (189). ECS
      network follows a scale-free topology, which confers robustness against random
      damage, easy navigability, and controllability. Network topological parameters,
      such as clustering coefficient (i.e., how the nodes form clusters) of 0.0009,
      network diameter (the longest shortest path among all pairs of nodes) of 12,
      averaged number of neighbors (the mean number of connections per node) of 3.073,
      and characteristic path length (the expected distance between two connected
      nodes) of 4.715, suggested that molecular messages are transferred through the
      ECS network quickly and specifically. Interestingly, ~75% of nodes are located
      on, or are active at the level of, the cell membrane. The hubs of ECS network are
      anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which have also the highest
      value of betweeness centrality, and their removal causes network collapse into
      multiple disconnected components. Importantly, AEA is a ubiquitous player while 2
      AG plays more restricted actions. Instead, the product of their degradation,
      arachidonic acid, and their hydrolyzing enzyme, fatty acid amide hydrolase, FAAH,
      have a marginal impact on ECS network, indeed their removal did not significantly
      affect its topology.

PMID- 24117402
TI  - Race and sex differences in small-molecule metabolites and metabolic hormones in
      overweight and obese adults.
AB  - In overweight/obese individuals, cardiometabolic risk factors differ by race and
      sex categories. Small-molecule metabolites and metabolic hormone levels might
      also differ across these categories and contribute to risk factor heterogeneity.
      To explore this possibility, we performed a cross-sectional analysis of fasting
      plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500
      overweight/obese adults who participated in the Weight Loss Maintenance trial.
      Principal-components analysis (PCA) was used for reduction of metabolite data.
      Race and sex-stratified comparisons of metabolite factors and metabolic hormones
      were performed. African Americans represented 37.4% of the study participants,
      and females 63.0%. Of thirteen metabolite factors identified, three differed by
      race and sex: levels of factor 3 (branched-chain amino acids and related
      metabolites, p<0.0001), factor 6 (long-chain acylcarnitines, p<0.01), and factor
      2 (medium-chain dicarboxylated acylcarnitines, p<0.0001) were higher in males vs.
      females; factor 6 levels were higher in Caucasians vs. African Americans
      (p<0.0001). Significant differences were also observed in hormones regulating
      body weight homeostasis. Among overweight/obese adults, there are significant
      race and sex differences in small-molecule metabolites and metabolic hormones;
      these differences may contribute to risk factor heterogeneity across race and sex
      subgroups and should be considered in future investigations with circulating
      metabolites and metabolic hormones.

PMID- 24117403
TI  - Sleep apnoea patients have higher mortality when confronting sepsis.
AB  - BACKGROUND: Sleep is essential for the maintenance of an intact immune function.
      Patients with sleep apnoea experience frequent sleep interruption due to apnoea
      related arousals, possibly adversely impacting their immunity and affecting their
      outcomes when confronting sepsis. This case-control study aimed to compare the
      outcomes of sepsis patients with and without sleep apnoea. METHODS: From 2000 to
      2009, 168 sleep apnoea patients who were first admitted for sepsis were
      identified from the Taiwan National Health Insurance Research Database. Also, 672
      sepsis patients without sleep apnoea, who were matched by age, gender and
      Charlson's comorbidity index scores, served as controls. Hospital outcomes of the
      two groups were compared. Binary logistic regression was employed for
      multivariate analysis. RESULTS: The mortality rates of sepsis patients with and
      without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After
      multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P =
      0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number
      of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found
      to be independently associated with mortality. Sleep apnoea patients who needed
      continuous positive airway pressure treatment had an even higher risk of
      mortality. CONCLUSIONS: Sepsis patients with sleep apnoea may have poorer
      hospital outcomes than those without sleep apnoea.

PMID- 24117404
TI  - Getting a scientific paper published in Epilepsia: an editor's perspective.
AB  - Getting a paper published in Epilepsia depends first and foremost on the quality
      of the work reported, and on the clarity and convincingness of the presentation.
      Papers should focus on important and interesting topics with clearly stated
      objectives and goals. The observations and findings are of greatest interest when
      they are novel and change our views on the mechanisms and/or treatment of an
      epileptic disease. Studies should be carefully designed to include adequate
      sample size, comparison groups, and statistical analyses. Critically, the data
      must be clearly presented and appropriately interpreted. If followed, these
      recommendations will improve an author's chances of having his/her paper accepted
      in a high quality journal like Epilepsia. 

PMID- 24117405
TI  - Evaluating the extent of intramolecular charge transfer in the excited states of
      rhenium(I) donor-acceptor complexes with time-resolved vibrational spectroscopy.
AB  - Excited states in transition-metal complexes, even in those featuring ligands
      with strong electron donating and accepting properties, often involve only
      partial charge transfer between the donor and acceptor ligands. The excited-state
      properties of [Re(bpy)(CO)3L](+) compounds were studied, where L is 4
      dimethylaminobenzonitrile (Re4DMABN), 3-dimethylaminobenzonitrile (Re3DMABN), and
      benzonitrile (ReBN) using time-resolved infrared (TRIR) and electronic
      spectroscopy methods as well as electronic structure computations. The DMABN
      complexes exhibit strongly solvent-dependent luminescence; the excited state
      lifetime decreases from microseconds in dichloromethane to several nanoseconds in
      mixed MeOH:DCM (1:1) solvent. Despite the similarities in the solvent dependence
      of the excited state dynamics and redox properties for Re3DMABN and Re4DMABN, the
      nature of the lowest energy excited states formed in these two compounds is
      drastically different. For example, the lowest energy excited state for Re4DMABN
      in the mixed solvent is assigned to the (4DMABN -> bpy) ligand-to-ligand charge
      transfer (LLCT) state featuring partial charge transfer character. An equilibrium
      between a 3DMABN intraligand triplet ((3)IL) and a metal-ligand-to-ligand charge
      transfer (MLLCT) state is found for Re3DMABN in the mixed solvent with the latter
      at ca. 400 cm(-1) lower energy. The origin of such a drastic difference between
      the states involved in Re4DMABN and Re3DMABN is attributed to a difference in the
      energies of polarized quinoidal resonance structures in 4DMABN and 3DMABN
      ligands. 

PMID- 24117406
TI  - The association of GM-CSF -677A/C promoter gene polymorphism with the occurrence
      and severity of atopic dermatitis in a Polish population.

PMID- 24117407
TI  - Selective, bead-based global peptide capture using a bifunctional cross-linker.
AB  - Peptides are important species for a variety of biological functions. Detection
      and analysis of these molecules can be complicated by the presence of background
      matrix or contaminants. Therefore, a selective method to capture peptides could
      provide researchers with an option to isolate these remarkable species. Our goal
      was to perform a set of experiments that would validate the concept of a novel,
      selective peptide capture, whereby peptides are isolated on functionalized
      magnetic beads through the use of the heterobifunctional cross-linker, Sulfo-LC
      SPDP. Matrix assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) was used to monitor mass changes associated with the
      cross-linking reaction. MALDI-TOF MS was then used to monitor conjugation between
      the cross-linked peptides and sulfhydryl magnetic beads by analyzing supernatant
      solutions for the presence or absence of cross-linked peptide. Through these
      experiments, we have proof of concept data confirming that peptides can be
      isolated on sulfhydryl magnetic beads by using Sulfo-LC-SPDP. This method is a
      suitable selective global peptide isolation strategy to separate the molecules
      from contaminating species or sample matrix. This novel method has a variety of
      potential applications and detection methods. 

PMID- 24117409
TI  - Genome editing using artificial site-specific nucleases in zebrafish.
AB  - Zebrafish is a model vertebrate suitable for genetic analysis. Forward genetic
      analysis via chemical mutagenesis screening has established a variety of
      zebrafish mutants that are defective in various types of organogenesis, and the
      genes responsible for the individual mutants have been identified from genome
      mapping. On the other hand, reverse genetic analysis via targeted gene disruption
      using embryonic stem (ES) cells (e.g., knockout mouse) can uncover gene functions
      by investigating the phenotypic effects. However, this approach is mostly limited
      to mice among the vertebrate models because of the difficulty in establishing ES
      cells. Recently, new gene targeting technologies, such as the transcription
      activator-like effector nucleases (TALEN) and clustered regularly interspaced
      short palindromic repeats (CRISPR)/Cas9 systems, have been developed: that can
      directly introduce genome modifications at the targeted genomic locus. Here, we
      summarize these new and powerful genome editing techniques for the study of
      zebrafish. 

PMID- 24117408
TI  - Toddlers default to canonical surface-to-meaning mapping when learning verbs.
AB  - Previous work has shown that toddlers readily encode each noun in the sentence as
      a distinct argument of the verb. However, languages allow multiple mappings
      between form and meaning that do not fit this canonical format. Two experiments
      examined French 28-month-olds' interpretation of right-dislocated sentences
      (nouni -verb, nouni) where the presence of clear, language-specific cues should
      block such a canonical mapping. Toddlers (N = 96) interpreted novel verbs
      embedded in these sentences as transitive, disregarding prosodic cues to
      dislocation (Experiment 1) but correctly interpreted right-dislocated sentences
      containing well-known verbs (Experiment 2). These results suggest that toddlers
      can integrate multiple cues in ideal conditions, but default to canonical surface
      to-meaning mapping when extracting structural information about novel verbs in
      semantically impoverished conditions.

PMID- 24117410
TI  - Metabolomic by 1H NMR spectroscopy differentiates "Fiano di Avellino" white wines
      obtained with different yeast strains.
AB  - We employed (1)H NMR spectroscopy to examine the molecular profile of a white
      "Fiano di Avellino" wine obtained through fermentation by either a commercial or
      a selected autochthonous Saccharomyces cerevisiae yeast starter. The latter was
      isolated from the same grape variety used in the wine-making process in order to
      strengthen the relationship between wine molecular quality and its geographical
      origin. (1)H NMR spectra, where water and ethanol signals were suppressed by a
      presaturated T1-edited NMR pulse sequence, allowed for definition of the
      metabolic content of the two differently treated wines. Elaboration of NMR
      spectral data by multivariate statistical analyses showed that the two different
      yeasts led to significant diversity in the wine metabolomes. Our results indicate
      that metabolomics by (1)H NMR spectroscopy combined with multivariate statistical
      analysis enables wine differentiation as a function of yeast species and other
      wine-making factors, thereby contributing to objectively relate wine quality to
      the terroir. 

PMID- 24117411
TI  - Muir-Torre Syndrome in a Middle-Aged Chinese Patient with Sebaceous Carcinoma of
      the Eyelid.
AB  - Muir-Torre syndrome is a rare, autosomal dominant condition characterized by the
      presence of a skin tumor of sebaceous differentiation and visceral malignancies.
      We reviewed the case of a 46-year-old Chinese man who had a bleeding mass over
      the right upper eyelid. He had a history of colon cancer and a family history
      satisfying the Amsterdam criteria for hereditary non-polyposis colorectal cancer
      syndrome with germline mutation in the MutS homolog-2 gene. The eyelid lesion was
      excised completely and submitted for histopathologic examination which showed
      sebaceous carcinoma. Frozen section and conjunctival map biopsy showed no
      residual malignancy or local metastasis. Post-operative positron-emission
      tomography with combined computed tomography did not reveal any residual or
      visceral malignancy. He had no recurrence in the 32-month follow-up period. We
      should consider Muir-Torre syndrome in patients with sebaceous carcinoma,
      especially in the presence of personal and/or family history of visceral
      malignancies. 

PMID- 24117412
TI  - Prospective comparison of low-fluence photodynamic therapy combined with
      intravitreal bevacizumab versus bevacizumab monotherapy for choroidal
      neovascularization in age-related macular degeneration.
AB  - PURPOSE: To evaluate combination treatment with reduced-fluence photodynamic
      therapy (RDPDT) with Verteporfin and intravitreal bevacizumab, compared to
      bevacizumab alone, for choroidal neovascularization (CNV) in age-related macular
      degeneration. METHODS: This was a prospective, randomized comparative study
      comprising 95 patients with CNV. 49 patients received RDPDT (25 J/cm(2)) followed
      by intravitreal bevacizumab 1.25 mg one hour later, while 46 received
      intravitreal bevacizumab alone. Patients were followed for 12 months at four-week
      intervals with visual acuity (VA) assessment and Optical Coherence Tomography
      (OCT) of the macula. Bevacizumab re-injections were performed as needed. RESULTS:
      On average, patients were re-injected 4.45 times in the combination group and
      6.96 times in the bavacizumab group (p < 0.001). At 12 months, VA improved by
      8.64 letters in the bevacizumab group and by 8.37 letters in the combination
      group (p = 0.922). CONCLUSION: Adding a reduced-fluence PDT arm in combination
      with bevacizumab offers similar results to those of intravitreal bevacizumab
      alone with significantly reduced number of injection repetitions.

PMID- 24117413
TI  - Boston type I keratoprosthesis for treatment of gelatinous drop-like corneal
      dystrophy after repeated graft failure.
AB  - PURPOSE: To describe the use of a Boston type I keratoprosthesis as a secondary
      penetrating procedure to treat gelatinous drop-like corneal dystrophy (GDLD),
      with presentation of pathologic findings, genetic analysis, and discussion of
      other surgical options. METHODS: A 43-year-old woman with GDLD in both eyes, best
      corrected visual acuity (BCVA) of counting fingers in both eyes, and recurrent
      corneal opacification following two penetrating keratoplasties presented for
      visual rehabilitation. A Boston type I keratoprosthesis was implanted in her left
      eye after extracapsular clear lens extraction. RESULTS: The surgery was
      uneventful and one month after surgery, best corrected vision improved to 20/30,
      which has been maintained for a period of more than nine months. At the 12-month
      visit, her vision was noted to be diminished to 20/200 due to a retroprosthetic
      membrane and improved to 20/25 two weeks after a Yag capsulotomy. Histopathologic
      examination of the corneal specimen disclosed predominantly subepithelial amyloid
      deposition. Genetic analysis is presented. CONCLUSIONS: GDLD is a rare disorder
      of primary corneal amyloidosis. Recurrence of this condition following surgery is
      very common. Boston type I keratoprosthesis as a secondary procedure can be
      successful in restoring vision in affected patients.

PMID- 24117414
TI  - Fortune favours the bold: a higher predator reduces the impact of a native but
      not an invasive intermediate predator.
AB  - Emergent multiple predator effects (MPEs) might radically alter predictions of
      predatory impact that are based solely on the impact of individuals. In the
      context of biological invasions, determining if and how the individual-level
      impacts of invasive predators relates to their impacts in multiple-individual
      situations will inform understanding of how such impacts might propagate through
      recipient communities. Here, we use functional responses (the relationship
      between prey consumption rate and prey density) to compare the impacts of the
      invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart
      Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in
      conspecific groups and (iii) in conspecific groups in the presence of a higher
      fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the
      invader consumed significantly more basal prey than the native, and consumption
      was additive for both mysid species - that is, group consumption was predictable
      from individual-level consumption. Invaders and natives were themselves equally
      susceptible to predation when feeding with the higher fish predator, but an MPE
      occurred only between the natives and higher predator, where consumption of basal
      prey was significantly reduced. In contrast, consumption by the invaders and
      higher predator remained additive. The presence of a higher predator serves to
      exacerbate the existing difference in individual-level consumption between
      invasive and native mysids. We attribute the mechanism responsible for the MPE
      associated with the native to a trait-mediated indirect interaction, and further
      suggest that the relative indifference to predator threat on the part of the
      invader contributes to its success and impacts within invaded communities. 

PMID- 24117415
TI  - Laser dermatology - beware the sharks!

PMID- 24117416
TI  - Linking social and pathogen transmission networks using microbial genetics in
      giraffe (Giraffa camelopardalis).
AB  - Although network analysis has drawn considerable attention as a promising tool
      for disease ecology, empirical research has been hindered by limitations in
      detecting the occurrence of pathogen transmission (who transmitted to whom)
      within social networks. Using a novel approach, we utilize the genetics of a
      diverse microbe, Escherichia coli, to infer where direct or indirect transmission
      has occurred and use these data to construct transmission networks for a wild
      giraffe population (Giraffe camelopardalis). Individuals were considered to be a
      part of the same transmission chain and were interlinked in the transmission
      network if they shared genetic subtypes of E. coli. By using microbial genetics
      to quantify who transmits to whom independently from the behavioural data on who
      is in contact with whom, we were able to directly investigate how the structure
      of contact networks influences the structure of the transmission network. To
      distinguish between the effects of social and environmental contact on
      transmission dynamics, the transmission network was compared with two separate
      contact networks defined from the behavioural data: a social network based on
      association patterns, and a spatial network based on patterns of home-range
      overlap among individuals. We found that links in the transmission network were
      more likely to occur between individuals that were strongly linked in the social
      network. Furthermore, individuals that had more numerous connections or that
      occupied 'bottleneck' positions in the social network tended to occupy similar
      positions in the transmission network. No similar correlations were observed
      between the spatial and transmission networks. This indicates that an
      individual's social network position is predictive of transmission network
      position, which has implications for identifying individuals that function as
      super-spreaders or transmission bottlenecks in the population. These results
      emphasize the importance of association patterns in understanding transmission
      dynamics, even for environmentally transmitted microbes like E. coli. This study
      is the first to use microbial genetics to construct and analyse transmission
      networks in a wildlife population and highlights the potential utility of an
      approach integrating microbial genetics with network analysis.

PMID- 24117417
TI  - Statistical tests for measures of colocalization in biological microscopy.
AB  - Colocalization analysis is the most common technique used for quantitative
      analysis of fluorescence microscopy images. Several metrics have been developed
      for measuring the colocalization of two probes, including Pearson's correlation
      coefficient (PCC) and Manders' correlation coefficient (MCC). However, once
      measured, the meaning of these measurements can be unclear; interpreting PCC or
      MCC values requires the ability to evaluate the significance of a particular
      measurement, or the significance of the difference between two sets of
      measurements. In previous work, we showed how spatial autocorrelation confounds
      randomization techniques commonly used for statistical analysis of colocalization
      data. Here we use computer simulations of biological images to show that the
      Student's one-sample t-test can be used to test the significance of PCC or MCC
      measurements of colocalization, and the Student's two-sample t-test can be used
      to test the significance of the difference between measurements obtained under
      different experimental conditions. 

PMID- 24117418
TI  - Outer-selective pressure-retarded osmosis hollow fiber membranes from vacuum
      assisted interfacial polymerization for osmotic power generation.
AB  - In this paper, we report the technical breakthroughs to synthesize outer
      selective thin-film composite (TFC) hollow fiber membranes, which is in an urgent
      need for osmotic power generation with the pressure-retarded osmosis (PRO)
      process. In the first step, a defect-free thin-film composite membrane module is
      achieved by vacuum-assisted interfacial polymerization. The PRO performance is
      further enhanced by optimizing the support in terms of pore size and mechanical
      strength and the TFC layer with polydopamine coating and molecular engineering of
      the interfacial polymerization solution. The newly developed membranes can stand
      over 20 bar with a peak power density of 7.63 W/m(2), which is equivalent to
      13.72 W/m(2) of its inner-selective hollow fiber counterpart with the same module
      size, packing density, and fiber dimensions. The study may provide insightful
      guidelines for optimizing the interfacial polymerization procedures and scaling
      up of the outer-selective TFC hollow fiber membrane modules for PRO power
      generation. 

PMID- 24117419
TI  - Challenges of treating patients with chronic pain with dysphagia (CPD): physician
      and patient perspectives.
AB  - OBJECTIVE: Dysphagia--difficulty eating and swallowing--can significantly impair
      a patient's ability to maintain adequate nutritional and medication intake. There
      are a large number of patients with chronic pain, including pediatric, geriatric,
      and palliative care patients, who suffer from dysphagia and, therefore, have
      difficulty achieving optimal pain management with solid, oral formulations. The
      objective of this study was to survey physicians and patients in the US to
      understand their knowledge, attitudes, and clinical management/analgesic usage
      patterns in the treatment of patients with chronic pain with dysphagia (CPD).
      RESEARCH DESIGN AND METHODS: Two separate surveys were administered to physicians
      and patients. The physician survey design was qualitative; physicians
      participated in a semi-structured phone interview. The patient survey design was
      quantitative; patients participated in a structured online survey. Purposive
      sampling was used to recruit participants into both studies. Physician
      participants were identified based on their specialty, prescribing practices, and
      geographic location. Patient participants were recruited through a consumer panel
      of pre-identified individuals who, for 3 months or longer, had chronic pain and
      were taking opioids. RESULTS: Thirty-four physicians and 1021 patients were
      surveyed. Physicians indicated that 5-20% of their patients had difficulty
      swallowing. Treatment for CPD consisted of the fentanyl patch, immediate-release
      opioids, methadone liquid, or extended-release morphine products. Physicians were
      not satisfied with currently available treatment options. Twenty-nine per cent of
      patients surveyed had trouble swallowing or disliked swallowing pills. Eighty per
      cent of patients were not asked about their ability to swallow solid, oral dosage
      forms by their physician. To circumvent swallowing difficulties, some patients
      (16%) cut/crush/grind their medication to facilitate swallowing. Most of these
      patients (65%) did not know that altering tablets could potentially change the
      drug release (pharmacokinetic) characteristics of the tablet and lead to serious
      adverse events. LIMITATIONS: Qualitative survey research can be influenced by
      responder bias as well as selection bias. The number of survey participants for
      both the physician and patient surveys was small, thus responses may not reflect
      those in the general population. CONCLUSION: A proportion of patients with
      chronic pain have dysphagia and cannot swallow solid, oral dosage forms, which
      creates a serious treatment challenge for pain specialists and other healthcare
      providers. Currently available treatment options have limitations; new treatment
      options would be welcomed by both physicians and patients. Physician and patient
      education should be enhanced in order to promote awareness of the deleterious
      consequences associated with altering currently available analgesic formulations.
      Facilitating patient-physician communication on this topic may help to improve
      treatment outcomes.

PMID- 24117420
TI  - Mechanism of rhodium-catalyzed carbon-silicon bond cleavage for the synthesis of
      benzosilole derivatives: a computational study.
AB  - Rhodium-catalyzed carbon-silicon bond cleavage reaction is an efficient approach
      for the synthesis of silole derivates. The newly reported density functional
      theory method M11 is employed in order to elucidate how to cleave the inactive
      C(methyl)-Si bond. The computational results indicate that oxidative
      addition/reductive elimination pathway is favored over direct transmetallation in
      the C(methyl)-Si bond cleavage step. Alternatively, 1,4-rhodium-silicon exchange
      could take place before oxidative addition/reductive elimination. The rate
      determining step for both pathways has been targeted on the initial
      transmetallation of 2-trimethylsilylphenyl boronic acid. The active catalytic
      species is a monomeric hydroxyrhodium complex, which could be regenerated from
      the hydrolysis of methylrhodium complex. In addition, theoretical calculations
      show that the hydrolyses of both aryl and vinyl intermediates are inhibited by
      intramolecular pi-coordinated groups. 

PMID- 24117421
TI  - Palladium-catalyzed cascade oxidation/sp2 C-H acylation of azoarenes with aryl
      methanes.
AB  - A Pd-catalyzed cascade oxidation/sp(2) C-H bond acylation of azoarenes was
      developed in which readily available aryl methanes were used as the in situ
      generated acyl sources. This reaction provides a convenient access to ortho-acyl
      azoarenes under mild conditions. 

PMID- 24117422
TI  - SETBP1 mutations in juvenile myelomonocytic leukaemia and myelodysplastic
      syndrome but not in paediatric acute myeloid leukaemia.

PMID- 24117423
TI  - Brush-first and click: efficient synthesis of nanoparticles that degrade and
      release doxorubicin in response to light.
AB  - New strategies for the synthesis of multifunctional particles that respond to
      external stimuli and release biologically relevant agents will enable the
      discovery of new formulations for drug delivery. In this article, we combine two
      powerful methods: brush-first ring-opening metathesis polymerization and copper
      catalyzed azide-alkyne cycloaddition click chemistry, for the synthesis of a
      novel class of brush-arm star polymers (BASPs) that simultaneously degrade and
      release the anticancer drug doxorubicin (DOX) in response to 365 nm light. In
      vitro cell viability studies were performed to study the toxicity of azide- and
      DOX-loaded BASPs. The former were completely nontoxic. The latter showed minimal
      toxicity in the absence of light; UV-triggered DOX release led to IC50 values
      that were similar to that of free DOX.

PMID- 24117424
TI  - Variations of the chemical composition and bioactivity of essential oils from
      leaves and stems of Liquidambar styraciflua (Altingiaceae).
AB  - OBJECTIVES: This study aimed to evaluate the variations of the chemical
      composition and bioactivity of essential oils of Liquidambar styraciflua L.
      (Altingiaceae) collected in different seasons. METHODS: The oils were analysed by
      GLC/FID and GLC/MS. The antioxidant activity was investigated by
      diphenylpicrylhydrazyl (DPPH) and superoxide anion radical scavenging assays and
      the deoxyribose degradation assay. Inhibition of both 5-lipoxygenase (5-LOX) and
      prostaglandin E2 (PGE2) production in hepatic cancer (HepG-2) cells were used to
      assess the anti-inflammatory activity. The cytotoxic activity was investigated
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      KEY FINDINGS: Altogether, 64 volatile secondary metabolites were identified. The
      major components of the leaf oil were d-limonene, alpha-pinene and beta-pinene,
      and of the stem oil were germacrine D, alpha-cadinol, d-limonene, alpha-pinene,
      and beta-pinene. Leaf and stem oils collected in spring could reduce DPPH? (IC50
      = 3.17 and 2.19 mg/ml) and prevent the degradation of the deoxyribose sugar (IC50
      = 17.55 and 14.29 MUg/ml). The stem oil exhibited a higher inhibition of both 5
      LOX and PGE2 than the leaf oil. The cytotoxic activity of leaf and stem oils was
      low in cancer cell lines (IC50 = 136.27 and 119.78 MUg/ml in cervical cancer
      (HeLa) cells). CONCLUSIONS: Essential oils of L. styraciflua exhibited an
      interesting anti-inflammatory activity with low cytotoxicity, supporting its
      traditional use to treat inflammation.

PMID- 24117425
TI  - Enhancing medical compliance of patients with convulsive epilepsy in rural
      community: a randomized intervention trial.
AB  - PURPOSE: This randomized intervention trial was to determine whether the
      implementation of a practical intervention was effective in enhancing medical
      compliance and improving seizure control among patients with convulsive epilepsy
      in rural communities in western China. METHODS: Two of four areas were randomly
      selected for this study and assigned to be the intervention group (IG) and the
      control group (CG), respectively. An intervention package with four components
      (intensive education, consultation services, maintenance of an epilepsy tracking
      card, and repeated reminders) was formulated. Medical compliance included
      antiepileptic drug (AED) adherence and lifestyle; each was graded on a 6-point
      scale with possible scores. Medical compliance and seizure control were measured
      and compared between the groups before and after the intervention. In addition,
      correlation of both changes in medical compliance and seizure frequency were
      investigated. KEY FINDINGS: After 1-year follow-up, 183 patients in the IG (105
      male) and 177 in the CG (99 male) remained for the analysis. At the end of the
      study, the average number of seizures in the IG declined 18.3% compared to that
      prior to the intervention (after 6-month phenobarbital monotherapy), nearly twice
      as much as in CG (9.1%) with statistical difference (p = 0.023). The proportion
      of patients with a reduction in seizures >50% (including those who were seizure
      free) rose to 79.8% in the IG compared to 61.0% in the CG (p < 0.05). With regard
      to medical compliance, the majority of the IG members were rated as excellent or
      very good, but medical compliance remained nearly unchanged for the CG. A
      moderate correlation was found between the changes in AED adherence and seizure
      control (r = 0.4, p < 0.05), and a weaker correlation was found between lifestyle
      and seizure control (r = 0.328, p < 0.05). SIGNIFICANCE: This intervention
      package proved to be efficient in enhancing medical compliance and improving
      seizure control in rural communities of resource-poor areas.

PMID- 24117427
TI  - Preface--Contributions to the 8th International Conference on Applications of
      Stable Isotope Techniques to Ecological Studies (ISOECOL), Brest, France, 20-24
      August 2012.

PMID- 24117428
TI  - Carbon and nitrogen stable isotopes reveal the use of pelagic resources by the
      invasive Ponto-Caspian mysid Limnomysis benedeni.
AB  - The Ponto-Caspian mysid shrimp Limnomysis benedeni has rapidly invaded freshwater
      systems throughout Europe and is now found in extremely high abundances in
      invaded systems. However, very little is known about the trophic ecology of this
      mysid in invaded ecosystems, in particular the relative degree of herbivory,
      carnivory and detritivory of this potentially omnivorous species and where it
      derives its energy, i.e. via carbon fixed by algae inhabiting benthic or pelagic
      habitats or through allochthonous inputs. Here, we investigate the trophic
      ecology of L. benedeni in a recently established population in North-Western
      Germany using stable carbon and nitrogen isotopes. Our results suggest that in
      contrast to its previous classifications as a benthic or bentho-pelagic
      herbivore, L. benedeni is an omnivorous species, which can derive the bulk of its
      carbon from pelagic resources. Its trophic niche in different invaded ecosystems
      will be determined by multiple, system-dependent factors which have to be
      considered in order to predict the mysids' invasion potential. 

PMID- 24117426
TI  - Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme
      oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate the anti-hepatitis C virus
      (HCV) activity of andrographolide, a diterpenoid lactone extracted from
      Andrographis paniculata, and to identify the signalling pathway involved in its
      antiviral action. EXPERIMENTAL APPROACH: Using HCV replicon and HCVcc infectious
      systems, we identified anti-HCV activity of andrographolide by measuring protein
      and RNA levels. A reporter activity assay was used to determine transcriptional
      regulation of anti-HCV agents. A specific inhibitor and short hairpin RNAs were
      used to investigate the mechanism responsible for the effect of andrographolide
      on HCV replication. KEY RESULTS: In HCV replicon and HCVcc infectious systems,
      andrographolide time- and dose-dependently suppressed HCV replication. When
      combined with IFN-alpha, an inhibitor targeting HCV NS3/4A protease (telaprevir),
      or NS5B polymerase (PSI-7977), andrographolide exhibited a significant
      synergistic effect. Andrographolide up-regulated the expression of haeme
      oxygenase-1 (HO-1), leading to increased amounts of its metabolite biliverdin,
      which was found to suppress HCV replication by promoting the antiviral IFN
      responses and inhibiting NS3/4A protease activity. Significantly, these antiviral
      effects were attenuated by an HO-1-specific inhibitor or HO-1 gene knockdown,
      indicating that HO-1 contributed to the anti-HCV activity of andrographolide.
      Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear
      factor erythroid 2-related factor 2 (Nrf2)-mediated HO-1 expression, and this was
      found to be associated with its anti-HCV activity. CONCLUSIONS AND IMPLICATIONS:
      Our results demonstrate that andrographolide has the potential to control HCV
      replication and suggest that targeting the Nrf2-HO-1 signalling pathway might be
      a promising strategy for drug development.

PMID- 24117429
TI  - Intraspecific isotopic niche variation in broad-snouted caiman (Caiman
      latirostris).
AB  - Strategies to minimise intraspecific competition are common in wild animals. For
      example, individuals may exploit food resources at different levels of the food
      chain. Analyses of stable isotopes are particularly useful for confirming
      variations in an intraspecific niche because the chemical composition of animals
      tends to reflect both the food consumed and the habitats occupied by the species.
      However, studies using this methodology to investigate neotropical crocodilians
      are scarce. This study aimed to verify the existence of ontogenetic and sexual
      niche variation in broad-snouted caiman in a silvicultural landscape in Brazil
      through the use of carbon and nitrogen stable isotopes. The isotopic ratios of
      carbon and nitrogen were determined in claw samples collected from 24 juveniles,
      8 adults, and 16 hatchlings of C. latirostris. We identified a discrete
      ontogenetic variation in the isotopic niche and sexual difference only for
      juveniles. These results may indicate differences in the exploitation resources
      and a consequent reduction in competition between age classes. 

PMID- 24117430
TI  - Mechanistic studies of reactions catalysed by diamine oxidase using isotope
      effects.
AB  - Diamine oxidase (DAO), the enzyme that is responsible for amine biodegradation in
      animals, plants and humans, catalyses the biotransformation of amines such as
      histamine (HA), putrescine, 1-phenylethylamine, tyrosine, tryptamine, serotonine
      and spermine. The kinetic and solvent isotope effects (SIEs) were applied to
      study the mechanism of the biotransformation using HA and its methylderivatives.
      The SIE for the biotransformation of HA, N(tau)-methylhistamine and N(pi)
      methylhistamine was found to be 3.58, 2.22 and 5.70 on Vmax, and 1.58, 1.06 and
      1.14 on Vmax/KM, respectively. On the other hand, the kinetic isotope effect for
      oxidation of stereospecifically deuterium-labelled [(alpha R)-(2)H]-N(tau)
      methylhistamine and [(alpha R)-(2)H]-N(pi)-methylhistamine was 0.69 and 0.62 on
      Vmax, and 15.06 and 7.50 on Vmax/K(M), respectively. These results demonstrate
      that DAO catalyses amine biotransformation by stereospecifically cleaving the
      alphaC-H bond in the pro-S position. Moreover, the oxidation of amine to aldehyde
      involves several transition states, including hybridisation change from sp(3)
      (Schiff base) to sp(2) (imine), then back again to sp(3) to give a final product
      with hybridisation sp(2) (aldehyde).

PMID- 24117431
TI  - Measurement of stable isotope activities in saline aqueous solutions using
      optical spectroscopy methods.
AB  - The requirement to measure the stable isotopic compositions of saline pore fluids
      by optical methods has prompted a re-evaluation of the isotopic salt effect for
      common salts. Hydrogen and oxygen isotopic salt effects were measured at room
      temperature (21 degrees C) by optical methods. For hydrogen isotopes, our results
      agree well with those of previous studies and better define these effects at low
      temperatures. In contrast, measured oxygen isotope salt effects disagree within
      error for NaCl and CaCl2 solutions from those reported previously. Subtle
      differences between measurement methods may account for the discrepancy. In
      studies that involve highly saline fluids, the isotopic salt effect must be taken
      into account because modern methods that measure stable isotopic compositions as
      activities or concentrations may be not directly comparable to historical data
      sets. 

PMID- 24117432
TI  - Enhancement of prodigiosin production by Serratia marcescens TKU011 and its
      insecticidal activity relative to food colorants.
AB  - Prodigiosin (PG) has been reported to have various biological activities. With
      the aim of increasing Serratia marcescens TKU011 PG production on squid pen
      powder (SPP)-containing medium, the effects of phosphate and ferrous ion
      supplementation, autoclave treatment, and aeration were studied. Autoclave
      treatment showed positive results for PG productivity (2.48 mg/mL), which
      increased 2.5-fold when the organism was incubated in 50 mL of 40-min autoclaved
      medium in a baffle-based flask (250 mL) containing 1.5% SPP at 30  degrees C for
      1 day and then at 25  degrees C for 2 additional days. Furthermore, the use of
      pigments including PG and the food colorants Allura Red AC (R40) and Tartrazine
      (Y4) as insecticides was also investigated. The lethal concentrations causing 50%
      Drosophila larval mortality (LC50) of PG, Y4, and R40 using a 5-d exposure period
      were 230, 449, and 30000 ppm, respectively. The results indicated that the
      biopigment PG and the food colorant Y4 were potentially toxic to Drosophila
      larvae. 

PMID- 24117433
TI  - Polyhedral metal-imidazolate cages: control of self-assembly and cage to cage
      transformation.
AB  - A series of neutral cubic nickel(II)-imidazolate Ni8L12X4 cages were prepared by
      rational choices of substituents and anions with solvothermal subcomponent self
      assembly technology. Both substituents and halide anions play a critical role in
      the formation and stabilization of cubic cages. Changing one of the factors in
      the reaction will switch the final structure to a Ni14L24 rhombic dodecahedral
      cage. The cubic cage can transform to a large rhombic dodecahedral cage in the
      presence of methylamine at room temperature accompanied by a color change from
      purple to light yellow. 

PMID- 24117434
TI  - Murine dopaminergic Muller cells restore motor function in a model of Parkinson's
      disease.
AB  - Muller cells constitute the main glial cell type in the retina where it interacts
      with virtually all cells displaying relevant functions to retinal physiology.
      Under appropriate stimuli, Muller cells may undergo dedifferentiation, being able
      to generate other neural cell types. Here, we show that purified mouse Muller
      cells in culture express a group of proteins related to the dopaminergic
      phenotype, including the nuclear receptor-related 1 protein, required for
      dopaminergic differentiation, as well the enzyme tyrosine hydroxylase. These
      dopaminergic components are active, since Muller cells are able to synthesize and
      release dopamine to the extracellular medium. Moreover, Muller-derived tyrosine
      hydroxylase can be regulated, increasing its activity because of phosphorylation
      of serine residues in response to agents that increase intracellular cAMP levels.
      These observations were extended to glial cells obtained from adult monkey
      retinas with essentially the same results. To address the potential use of
      dopaminergic Muller cells as a source of dopamine in cell therapy procedures, we
      used a mouse model of Parkinson's disease, in which mouse Muller cells with the
      dopaminergic phenotype were transplanted into the striatum of hemi-parkinsonian
      mice generated by unilateral injection of 6-hydroxydopamine. These cells fully
      decreased the apomorphine-induced rotational behavior and restored motor
      functions in these animals, as measured by the rotarod and the forelimb-use
      asymmetry (cylinder) tests. The data indicate local restoration of dopaminergic
      signaling in hemi-parkinsonian mice confirmed by measurement of striatal dopamine
      after Muller cell grafting.

PMID- 24117435
TI  - Psoriasis and smoking: a systematic review and meta-analysis.
AB  - Psoriasis is an inflammatory skin disease associated with increased
      cardiovascular comorbidity. Smoking is associated with an increased risk of
      cardiovascular disease, and prior studies have suggested that patients with
      psoriasis are more likely to be active smokers. Smoking may also be a risk factor
      in the development of psoriasis. We conducted a systematic review and meta
      analysis to assess the prevalence of smoking among patients with psoriasis, and
      we reviewed the contribution of smoking to the incidence of psoriasis. A total of
      25 prevalence and three incidence studies were identified. The meta-analysis of
      prevalence studies included a total of 146 934 patients with psoriasis and 529
      111 patients without psoriasis. Random effects meta-analysis found an association
      between psoriasis and current smoking [pooled odds ratio (OR) 1.78, 95%
      confidence interval (CI) 1.52-2.06], as well as between psoriasis and former
      smoking (pooled OR 1.62, 95% CI 1.33-1.99). Meta-regression analysis did not
      reveal any sources of study heterogeneity, but a funnel plot suggested possible
      publication bias. A subset of studies also examined the association between
      moderate-to-severe psoriasis and smoking, with a pooled OR of 1.72 (95% CI 1.33
      2.22) for prevalent smoking. The three incidence studies found an association
      between smoking and incidence of psoriasis, with a possible dose-effect of
      smoking intensity and duration on psoriasis incidence. These findings suggest
      that smoking is an independent risk factor for the development of psoriasis, and
      that patients with established psoriasis continue to smoke more than patients
      without psoriasis.

PMID- 24117436
TI  - Improving allergy management in the primary care network--a holistic approach.
AB  - The incidence, prevalence and costs of allergy have increased substantially in
      recent decades in many parts of Europe. The dominant model of allergy care within
      Europe is at the moment specialist-based. This model will become unsustainable
      and undeliverable with increasing disease prevalence. One solution to increase
      provision of allergy services is to diversify the providers. A new model for the
      provision of allergy care in the community with the general practitioner at the
      forefront is proposed. Pre- and postgraduate allergy education and training,
      implementation of pathways of care, allergy specialization and political will to
      generate resources and support are essential to achieve this new model. In
      parallel the holistic view of allergic diseases should be maintained, including
      assessment of severity and risk, psychological factors and health-care related
      costs in the context of the patient-centered decision making process. 

PMID- 24117437
TI  - Contribution of parents' adult attachment and separation attitudes to parent
      adolescent conflict resolution.
AB  - This study examined the contribution to parent-adolescent conflict resolution of
      parental adult attachment styles and attitudes toward adolescent separation.
      Questionnaires were completed by 295 couples with early to late adolescent
      children. Structural equation models were used to test self and partner
      influences on conflict resolution for three attachment orientations: confidence
      (model A), anxiety (model B) and avoidance (model C). Model A showed self
      influences between parents' confidence orientation and negotiation and also via
      positive attitudes towards separation. Also, the fathers' use of negotiation was
      facilitated by the mothers' confidence orientation and vice versa, indicating
      partner influences as well. Model B showed self influences between parents'
      anxiety orientation and the use of dominance and withdrawal and also via negative
      attitudes towards separation. Model C showed self influences between parents'
      avoidance orientation and dominance and withdrawal, and a partner influence
      between fathers' avoidance and mothers' use of dominance. The results indicated
      that the parents' adult attachment system and the parenting system were related
      in the area of conflict resolution, and that self influences were stronger than
      partner influences. 

PMID- 24117438
TI  - Low dose bexarotene treatment rescues dopamine neurons and restores behavioral
      function in models of Parkinson's disease.
AB  - Nurr1 is a nuclear hormone receptor (NucHR) strongly implicated in the growth,
      maintenance, and survival of dopaminergic neurons. Nurr1 may be unable to bind
      ligands directly, but it forms heterodimers with other NucHRs that do. Using
      bioluminescence resonance energy transfer (BRET) assays to directly monitor
      interactions of Nurr1 with other NucHRs, we found the cancer drug bexarotene
      (Targretin, also LGD1069) displayed biased interactions with Nurr1-RXR
      heterodimers compared with RXR-RXR homodimers. Remarkably, at doses up to 100
      fold lower than those effective in rodent cancer models, bexarotene rescued
      dopamine neurons and reversed behavioral deficits in 6-hydroxydopamine (6-OHDA)
      lesioned rats. Compared to the high doses used in cancer therapy, low doses of
      bexarotene have significantly milder side effects including a reduced increase in
      plasma triglycerides and less suppression of thyroid function. On the basis of
      extrapolations from rat to human doses, we hypothesize that low oral doses of
      bexarotene may provide an effective and tolerated therapy for Parkinson's disease
      (PD). 

PMID- 24117439
TI  - Ziprasidone-induced hypersensitivity syndrome confirmed by reintroduction.

PMID- 24117440
TI  - Changes in breeding phenology and population size of birds.
AB  - Although the phenology of numerous organisms has advanced significantly in
      response to recent climate change, the life-history and population consequences
      of earlier reproduction remain poorly understood. We analysed extensive data on
      temporal change in laying date and clutch size of birds from Europe and North
      America to test whether these changes were related to recent trends in population
      size. Across studies, laying date advanced significantly, while clutch size did
      not change. However, within populations, changes in laying date and clutch size
      were positively correlated, implying that species which advanced their laying
      date the most were also those that increased their clutch size the most. Greater
      advances in laying date were associated with species that had multiple broods per
      season, lived in nonagricultural habitats and were herbivorous or predatory. The
      duration of the breeding season increased for multibrooded species and decreased
      for single-brooded species. Changes in laying date and clutch size were not
      related to changes in population size (for resident or migratory species). This
      suggests that, across a wide variety of species, mismatches in the timing of egg
      laying or numbers of offspring have had relatively little influence on population
      size compared with other aspects of phenology and life history. 

PMID- 24117441
TI  - AtSIA1 AND AtOSA1: two Abc1 proteins involved in oxidative stress responses and
      iron distribution within chloroplasts.
AB  - The Abc1 protein kinases are a large family of functionally diverse proteins with
      multiple roles in the regulation of respiration and oxidative stress tolerance. A
      functional characterization was carried out for AtSIA1, an Arabidopsis thaliana
      Abc1-like protein, focusing on its potential redundancy with its homolog AtOSA1.
      Both proteins are located within chloroplasts, even if a different subplastidial
      localization seems probable. The comparison of atsia1 and atosa1 mutants,
      atsia1/atosa1 double mutant and wild-type plants revealed a reduction in
      plastidial iron-containing proteins of the Cytb6 f complex in the mutants. Iron
      uptake from soil is not hampered in mutant lines, suggesting that AtSIA1 and
      AtOSA1 affect iron distribution within the chloroplast. Mutants accumulated more
      ferritin and superoxide, and showed reduced tolerance to reactive oxygen species
      (ROS), potentially indicating a basal role in oxidative stress. The mutants
      produced higher concentrations of plastochromanol and plastoquinones than wild
      type plants, but only atsia1 plants developed larger plastoglobules and contained
      higher concentrations of alpha- and gamma-tocopherol and VTE1. Taken together,
      these data suggest that AtSIA1 and AtOSA1 probably act in signaling pathways that
      influence responses to ROS production and oxidative stress. 

PMID- 24117442
TI  - Peripheral blood progenitor cell collection by two programs for autologous and
      allogeneic transplantation.
AB  - BACKGROUND: In the Spectra apheresis instrument (Terumo BCT), both manual
      (Spectra-MNC) and automated (Spectra-Auto) programs have been widely used to
      collect peripheral blood progenitor cells (PBPCs). However, direct comparison of
      these programs remains extremely limited. STUDY DESIGN AND METHODS: We
      investigated 188 collections and products from autologous (patient) and
      allogeneic (donor) subjects and analyzed a subset of 89 allogeneic collections
      and products. Twenty-nine subjects who received apheresis for 2 consecutive days
      using both programs were also evaluated with a paired crossover comparison.
      RESULTS: The two programs processed similar volumes, but run time was longer with
      Spectra-Auto. Yield and efficiency of CD34+ cell collection were similar between
      these programs in the whole cohort, although white blood cell (WBC) and
      mononuclear cell (MNC) yields were higher with Spectra-MNC. In the allogeneic
      cohort, yield and efficiency of WBC collection were greater in Spectra-MNC.
      However, collected WBCs, MNCs, and CD34+ cells were similar between these
      programs in paired comparison. Regardless of program, preapheresis peripheral
      WBC, MNC, and CD34+ cell counts correlated with the number of cells collected. In
      contrast, preapheresis WBC counts in the whole cohort were negatively correlated
      with collection efficiencies of CD34+ cells in Spectra-MNC but not Spectra-Auto.
      The products collected using Spectra-MNC contained more contaminating platelets
      (PLTs) than Spectra-Auto, with a corresponding reduction in postdonation
      circulating PLTs. CONCLUSION: Spectra-MNC and Spectra-Auto showed distinct
      features that should be considered on a case-by-case basis. Similar
      investigations should be undertaken as new collection platforms are introduced.

PMID- 24117443
TI  - Natural variation in epigenetic gene regulation and its effects on plant
      developmental traits.
AB  - In plants, epigenetic variation contributes to phenotypic differences in
      developmental traits. At the mechanistic level, this variation is conferred by
      DNA methylation and histone modifications. We describe several examples in which
      changes in gene expression caused by variation in DNA methylation lead to
      alterations in plant development. In these examples, the presence of repeated
      sequences or transposons within the promoters of the affected genes are
      associated with DNA methylation and gene inactivation. Small interfering RNAs
      expressed from these sequences recruit DNA methylation to the gene. Some of these
      methylated alleles are unstable giving rise to revertant sectors during mitosis
      and to progeny in which the methylated state is lost. However, others are stable
      for many generations and persist through speciation. These examples indicate that
      although DNA methylation influences gene expression, this is frequently dependent
      on classical changes to DNA sequence such as transposon insertions. By contrast,
      forms of histone methylation cause repression of gene expression that is stably
      inherited through mitosis but that can also be erased over time or during
      meiosis. A striking example involves the induction of flowering by exposure to
      low winter temperatures in Arabidopsis thaliana and its relatives. Histone
      methylation participates in repression of expression of an inhibitor of flowering
      during cold. In annual, semelparous species such as A. thaliana, this histone
      methylation is stably inherited through mitosis after return from cold to warm
      temperatures allowing the plant to flower continuously during spring and summer
      until it senesces. However, in perennial, iteroparous relatives the histone
      modification rapidly disappears when temperatures rise, allowing expression of
      the floral inhibitor to increase and limiting flowering to a short interval. In
      this case, epigenetic histone modifications control a key adaptive trait, and
      their pattern changes rapidly during evolution associated with life-history
      strategy. We discuss these examples of epigenetic developmental traits with
      emphasis on the underlying mechanisms, their stability, and adaptive value. 

PMID- 24117444
TI  - Dermoscopy uncovers clinically undetectable pigmentation in basal cell carcinoma.
AB  - BACKGROUND: The presence of pigmentation might influence the management of basal
      cell carcinoma (BCC), with pigmented BCC responding poorly to certain treatments.
      Clinical studies report on a generally lower frequency of pigmentation compared
      with dermoscopic and histopathological studies, but the true frequency at which
      pigmentation occurs in clinically nonpigmented BCC has not been studied in
      detail. OBJECTIVES: To compare the clinical and dermoscopic frequency of
      pigmentation in a series of histopathologically diagnosed BCCs and to correlate
      it with patient demographics, tumour location and histopathological subtype.
      METHODS: Clinical and dermoscopic images of histopathologically confirmed BCCs
      were retrospectively evaluated for the presence of pigmentation. Dichotomous
      outcome variables were clinically pigmented and dermoscopically pigmented BCC.
      All separate dermoscopic variables were included in the analysis. Differences in
      proportions were evaluated using Pearson's chi-square test. RESULTS: Five hundred
      and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female
      ratio of 1.35 : 1 were included in the study. Clinically, 295 tumours were judged
      as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29.8%).
      Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern (n =
      184, 36.3%), followed by multiple blue-grey dots/globules (n = 147, 29%) and
      maple-leaf-like areas (n = 70, 13.8%). Superficial tumours exhibited mainly maple
      leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC
      was most frequently typified by the presence of blue-grey ovoid nests.
      CONCLUSIONS: Dermoscopy allows detection of pigmentation in about 30% of
      clinically nonpigmented BCCs, providing additional information that may aid the
      clinical choice of adequate treatment modalities.

PMID- 24117445
TI  - Cultural socialization and ethnic pride among Mexican-origin adolescents during
      the transition to middle school.
AB  - The relation between cultural socialization and ethnic pride during the
      transition to middle school was examined for 674 fifth-grade students (50% boys;
      Mage = 10.4 years) of Mexican origin. The theoretical model guiding the study
      proposes that parent-child relationship quality is a resource in the transmission
      of cultural values from parent to child and that parental warmth promotes the
      child's positive response to cultural socialization. Results showed that mother
      and father cultural socialization predicted youth ethnic pride and that this
      relation was stronger when parents were high in warmth. The findings highlight
      the positive role parent cultural socialization may play in the development of
      adolescent ethnic pride. Furthermore, findings reveal the role of parent-child
      relationship quality in this process.

PMID- 24117446
TI  - Prevalence of cerebral palsy, co-occurring autism spectrum disorders, and motor
      functioning - Autism and Developmental Disabilities Monitoring Network, USA,
      2008.
AB  - AIM: The aim of this study was to report the prevalence and characteristics of
      children with cerebral palsy (CP). METHOD: Children with CP (n=451) were
      ascertained by the Autism and Developmental Disabilities Monitoring (ADDM)
      Network, a population-based, record-review surveillance system monitoring CP in
      four areas of the USA. Prevalence was calculated as the number of children with
      CP among all 8-year-old children residing in these areas in 2008. Motor function
      was categorized by Gross Motor Function Classification System level and walking
      ability. Co-occurring autism spectrum disorders (ASD) and epilepsy were
      ascertained using ADDM Network surveillance methodology. RESULTS: The period
      prevalence of CP for 2008 was 3.1 per 1000 8-year-old children (95% confidence
      interval 2.8-3.4). Approximately 58% of children walked independently. Co
      occurring ASD frequency was 6.9% and was higher (18.4%) among children with non
      spastic CP, particularly hypotonic CP. Co-occurring epilepsy frequency was 41%
      overall, did not differ by ASD status or CP subtype, and was highest (67%) among
      children with limited or no walking ability. INTERPRETATION: The prevalence of CP
      in childhood from US surveillance data has remained relatively constant, in the
      range of 3.1 to 3.6 per 1000, since 1996. The higher frequency of ASD in non
      spastic than in spastic subtypes of CP calls for closer examination.

PMID- 24117447
TI  - Fatal Streptococcus anginosus-associated pneumonia in a captive Sumatran
      orangutan (Pongo abelii).
AB  - BACKGROUND: Bacterial infections commonly affect the lungs and air sacs of
      orangutans; culture and identification is rarely performed and may have clinical
      relevance. METHODS: Necropsy, histopathology and bacterial culture were
      performend on a captive adult male Sumatran orangutan with chronic air
      sacculitis. Bacterial speciation was confirmed by sequencing of the 16s-23s
      ribosomal DNA spacer region. RESULTS: Necropsy revealed severe suppurative
      pneumonia. Moderate growth of Streptoccocus anginosus was recovered from the
      lungs. CONCLUSIONS: This is the first report of S. anginosus as a cause of fatal
      suppurative pneumonia in a non-human primate.

PMID- 24117448
TI  - Base-pairing energies of proton-bound homodimers determined by guided ion beam
      tandem mass spectrometry: application to cytosine and 5-substituted cytosines.
AB  - Base-pairing interactions in proton-bound dimers of cytosine (C(+).C) are the
      major forces responsible for stabilization of DNA i-motif conformations.
      Permethylation of cytosine in extended (CCG).(CGG)n trinucleotide repeats has
      been shown to cause fragile-X syndrome, the most widespread inherited cause of
      mental retardation in humans. Oligonucleotides containing 5-bromo- or 5
      fluorocytosine can bind to proteins that selectively bind methylated DNA,
      suggesting that halogenated cytosine damage products can potentially mimic
      methylation signals. However, the influence of methylation or halogenation on the
      base-pairing energies (BPEs) of proton-bound dimers of cytosine and their impact
      on the stability of DNA i-motif conformations is presently unknown. To address
      this, proton-bound homodimers of cytosine and 5-methyl-, 5-fluoro-, 5-bromo-, and
      5-iodocytosine are investigated in detail both experimentally and theoretically.
      The BPEs of proton-bound homodimers of cytosine and the modified cytosines are
      measured by threshold collision-induced dissociation (TCID) techniques. 5
      Methylation of cytosine is found to increase the BPE and would therefore tend to
      stabilize DNA i-motif conformations. In contrast, 5-halogenation lowers the BPE.
      However, the BPEs of the proton-bound 5-halocytosine homodimers examined here
      still significantly exceed that of Watson-Crick G.C base pairs, such that DNA i
      motif conformations should be preserved in the presence of these modifications.
      Excellent agreement between TCID measured and B3LYP calculated BPEs is found,
      suggesting that B3LYP calculations can be used to provide reliable energetic
      predictions for related systems. 

PMID- 24117449
TI  - In vitro passages impact on virulence of Saprolegnia parasitica to Atlantic
      salmon, Salmo salar L. parr.
AB  - The effect of serial in vitro subculturing on three pathogenic strains of
      Saprolegnia parasitica was investigated. The isolates were passed through
      Atlantic salmon, Salmo salar L. parr, and then re-isolated as single spore
      colonies. All strains caused infection. The isolate obtained from diseased fish
      served as a virulent reference culture and was designated 'AP' ('activated
      through passage'). Successive subculturing was made by obtaining an inoculum from
      AP to produce the 2nd subculture and then passaged to the 3rd subculture (from
      the 2nd), until the 15th passage was obtained. Spores used to produce storage
      cultures were collected at passages 5, 10 and 15. The different passages of each
      strain were used to artificially infect Atlantic salmon parr. Morphological
      characterization of growth patterns was performed to observe differences
      occurring due to serial in vitro subculturing. Two of the strains declined in
      virulence after 15 successive in vitro subcultures, whereas one did not. This
      study is the first to investigate attenuation of virulence in Saprolegnia and
      whether or not isolates of S. parasitica should be passed through the fish host
      prior to challenge experiments. It reveals that some strains degenerate more
      rapidly than others when subjected to successive in vitro subculturing on glucose
      yeast extract. 

PMID- 24117450
TI  - Association study of DKK2 polymorphisms with alcohol dependence and alcohol
      related harm.
AB  - BACKGROUND: Alcohol dependence (AD) is a common disorder with both environmental
      and genetic factors. Previous studies have shown that the genomic region from
      chromosome 4q22-q32 is closely associated with AD. Furthermore, a study with
      Irish subjects revealed that the polymorphisms of Dickkopf WNT signaling pathway
      inhibitor (DKK2), located at 4q25, showed a significant association with AD.
      METHODS: We conducted a replication study of the association between DKK2
      polymorphisms and AD with 459 alcoholics and 444 normal controls, all of Korean
      descendent. To rank the AD of the subjects, Alcohol Use Disorders Identification
      Test (AUDIT) was utilized. Using the TaqMan assay, 21 single-nucleotide
      polymorphisms (SNPs) of DKK2 were genotyped. RESULTS: Our analysis showed that
      rs17037102 (Q146R) was significantly associated with overall AUDIT score (p =
      0.003, p(corr)  = 0.05 in dominant model). Further analysis showed that the SNP
      was significantly associated with alcohol-related harm (p = 0.001, p(corr)  =
      0.02 in co-dominant model). Several other SNPs, including the 3 SNPs which were
      associated with AD in European population, showed marginal associations that were
      erased when corrections for multiple testing was applied. Furthermore, rs17037102
      was in linkage disequilibrium with the nonexonic DKK2 SNPs which showed
      associations with AD in the previous study with Irish population, which suggests
      that rs17037102 may be the causal SNP. CONCLUSIONS: We found 1 DKK2 SNP to be
      significantly associated with alcohol-related harm in alcoholic subjects. The SNP
      might be the causal SNP which led its linked SNPs to show associations in
      previous studies.

PMID- 24117451
TI  - Serpiginous choroiditis with atypical presentation treated with intravenous
      methyl prednisolone.
AB  - PURPOSE: The purpose of this study is to report a case of atypical serpiginous
      choroiditis presenting with disc edema and exudative retinal detachment, treated
      successfully with intravenous methyl prednisolone. METHODS: A 45-year-old male
      patient presented with sudden decrease of vision in his left eye. On examination,
      left eye showed disc edema, exudative retinal detachment, and active serpiginous
      choroiditis. He was treated with intravenous methyl prednisolone followed by oral
      steroids and Azathioprine. RESULTS: At six weeks of follow-up, the choroiditis
      resolved completely with improvement of visual acuity. CONCLUSION: Atypical
      presentations of serpiginous choroiditis can cause diagnostic dilemma, but prompt
      diagnosis and immediate treatment can result in good visual recovery.

PMID- 24117452
TI  - Unusual adverse choroidal reaction to intravitreal bevacizumab in aggressive
      posterior retinopathy of prematurity: the Indian Twin Cities ROP screening
      (ITCROPS) data base report number 7.
AB  - PURPOSE: To describe a case of choroidal ischemia in a neonate after single,
      bilateral, intravitreal bevacizumab (IVB) injection for severe zone 1 aggressive
      posterior retinopathy of prematurity (AP-ROP). METHODS: A six-week-old baby, born
      at a gestation age of 28 weeks and birth weight of 1.08 kg, presented at a
      postconceptional age of 34 weeks for ROP screening. On examination, both eyes
      revealed engorged iris new vessels with poorly dilating pupils. Retinal
      examination showed media haze, severe zone 1 APROP with confluent new vessels,
      severe plus disease, and early vitreous condensation at the edge of new vessels
      for 12 clock hours. The child was treated bilaterally, with single IVB injection
      before laser. After 16 hours, hypotony and exudative retinal detachment with
      patches of choroidal whitening suggestive of choroidal ischemia were seen.
      RESULTS: The child was treated with topical steroids and cycloplegic drops and
      exudative retinal detachment resolved on the tenth day. Initial resolution of new
      vessels showed recurrence after two weeks and was treated with laser
      photocoagulation. Stable retinopathy status was noted up to six months follow-up.
      CONCLUSION: Choroidal ischemia secondary to a single IVB injection for the
      treatment of AP-ROP could be an unusual complication which raises the concern of
      its use as a monotherapy in neonates.

PMID- 24117453
TI  - Primary surgical excision for pediatric orbital capillary hemangioma.
AB  - We report the technique and outcome of surgical excision of subcutaneous orbital
      capillary hemangioma causing eye globe displacement in two children. Primary
      surgical excision was performed with blunt dissection along the tumor walls using
      a cotton-tipped applicator as the dissecting tool with simultaneous outward
      gentle traction on the tumor wall. Despite the deep and extensive orbital
      involvement, complete excision of the hemangiomas was achievable with this
      technique, which permitted excellent visualization of the surgical planes
      throughout the procedures. Deep and extensive pediatric orbital capillary
      hemangioma can be surgically excised with the suggested technique, which obviates
      the need for intralesional or systemic medical therapy, yielding optimal cosmetic
      and functional outcomes, shortly after surgery. 

PMID- 24117454
TI  - Flow dynamics of different adult ECMO systems: a clinical evaluation.
AB  - Membrane oxygenator (MO) failure is a known hazard during venovenous
      extracorporeal membrane oxygenation (v-v ECMO) therapy. Knowledge about technical
      and performance details of different ECMO systems (Maquet, Rastatt, Germany;
      Medos, Stolberg, Germany; Sorin, Modena, Italy) licensed for adults with acute
      lung failure might improve their handling. This retrospective study comprises 186
      adult patients (Regensburg ECMO Registry) treated with v-v ECMO. Flow dynamic
      data were used to analyze the performance of different blood pumps, cannula
      types, and MOs to maintain an adequate blood flow (1-5 L/min). Usage of the Medos
      ECMO system in critically ill patients required a higher pump speed and generated
      a higher pressure drop across the MO (dpMO), however, without an increase in free
      plasma hemoglobin. The dpMO depended on the type of MO and increased with blood
      flow as expected. Type-specific normal values are reported. A distinct increase
      in dpMO above normal values within 1 day required an immediate MO exchange. This
      was an infrequent technical complication (3%). Finally, pressure-flow performance
      of single dual-lumen cannulas (27 Fr) was comparable with small single-lumen
      cannulas (15 Fr), without an increased risk of technical-induced hemolysis.
      Despite different performances, all current commercially available adult v-v ECMO
      systems produce adequate blood flow without an increased risk in technical
      induced hemolysis. Familiarity with the specific properties of individual systems
      allows early detection of technical complications. Additionally, the choice of an
      adequate cannula requires a closer consideration of the individual patient
      situation. 

PMID- 24117455
TI  - Cryptochrome 1 regulates growth and development in Brassica through alteration in
      the expression of genes involved in light, phytohormone and stress signalling.
AB  - The blue light photoreceptors cryptochromes are ubiquitous in higher plants and
      are vital for regulating plant growth and development. In spite of being involved
      in controlling agronomically important traits like plant height and flowering
      time, cryptochromes have not been extensively characterized from agriculturally
      important crops. Here we show that overexpression of CRY1 from Brassica napus
      (BnCRY1), an oilseed crop, results in short-statured Brassica transgenics, likely
      to be less prone to wind and water lodging. The overexpression of BnCRY1
      accentuates the inhibition of cell elongation in hypocotyls of transgenic
      seedlings. The analysis of hypocotyl growth inhibition and anthocyanin
      accumulation responses in BnCRY1 overexpressors substantiates that regulation of
      seedling photomorphogenesis by cry1 is dependent on light intensity. This study
      highlights that the photoactivated cry1 acts through coordinated induction and
      suppression of specific downstream genes involved in phytohormone synthesis or
      signalling, and those involved in cell wall modification, during de-etiolation of
      Brassica seedlings. The microarray-based transcriptome profiling also suggests
      that the overexpression of BnCRY1 alters abiotic/biotic stress signalling
      pathways; the transgenic seedlings were apparently oversensitive to abscisic acid
      (ABA) and mannitol.

PMID- 24117456
TI  - Formulation and evaluation of Pheroid vesicles containing mefloquine for the
      treatment of malaria.
AB  - OBJECTIVES: Mefloquine (MQ) is an antimalarial drug with high efficacy, often
      used in the treatment and chemoprophylaxis of malaria. However, it has low
      solubility in water, a long elimination half-life (4 days), and is neurotoxic,
      which leads to unwanted side effects. METHODS: We investigated a lipid-based drug
      delivery system, Pheroid vesicles, in combination with MQ (Pheroid MQ), to
      promote future clinical use. MQ was incorporated into Pheroid vesicles and the
      formulations characterized. The formulations were evaluated in terms of in-vitro
      efficacy and toxicity. In-vivo bioavailability studies were conducted in C57 BL6
      mice. KEY FINDINGS: The vesicles incorporated MQ with ~63% entrapment efficiency.
      The IC50 values of MQ after 48-h incubation in chloroquine-resistant (RSA11) and
      chloroquine sensitive (3D7) strains, were reduced by ~50% and ~30% respectively.
      In-vivo bioavailability study revealed no change in the pharmacokinetic
      parameters of MQ, and the incorporation of the drug in Pheroid vesicles reduced
      the in-vitro haemolytic activity by ~75%. Furthermore, the cytotoxicity against
      human neuroblastoma cells (SH-SY5Y) of the free drug was reduced by ~64% with
      Pheroid MQ. CONCLUSIONS: Pheroid vesicles may therefore decrease the toxicity of
      MQ and thereby improve its therapeutic index, a strategy that may provide an
      effective alternative for malaria chemoprophylaxis and treatment.

PMID- 24117457
TI  - Ex vivo fluorescence confocal microscopy for fast evaluation of tumour margins
      during Mohs surgery.
AB  - BACKGROUND: Ex vivo fluorescence confocal microscopy (FCM) enables real-time
      imaging of skin morphology directly in freshly excised tissue. FCM displays wide
      field-of-view mosaics with cellular resolution, thus enabling a rapid bedside
      pathology. An application of interest is rapid detection of residual basal cell
      carcinoma (BCC) in skin excisions during Mohs surgery. OBJECTIVES: We sought to
      evaluate the sensitivity and specificity of ex vivo imaging with FCM for the
      detection of residual BCC in Mohs tissue excisions, and to calculate the time
      invested up to the diagnosis for both FCM and frozen sections. METHODS: Eighty
      consecutive BCCs were prospectively collected and the margins scanned with ex
      vivo FCM, including excisions with and without residual BCC of all major
      subtypes. Each mosaic was divided into two or four, resulting in 480 submosaics
      for study. Every confocal submosaic was assessed for the presence or absence of
      BCC and compared with standard frozen sections as the gold standard. Furthermore,
      the time spent for each technique was calculated and compared. RESULTS: The
      overall sensitivity and specificity of detecting residual BCC were 88% and 99%,
      respectively. Moreover, the new technique reduced by almost two-thirds the time
      invested when compared with the processing of a frozen section (P < 0.001).
      CONCLUSIONS: The results demonstrate the feasibility of confocal mosaicing
      microscopy in fresh tissue for rapid surgical pathology, potentially to expedite
      and guide Mohs surgery with high accuracy. This observation is an important step
      towards the goal of using real-time surgical pathology for skin tumours.

PMID- 24117459
TI  - Cadmium disorganises the scaffolding of gap and tight junction proteins in the
      hepatic cell line WIF B9.
AB  - BACKGROUND INFORMATION: Hepatocytes, which perform the main functions of the
      liver, are particularly vulnerable to toxic agents such as cadmium, an
      environmental pollutant. To identify the molecular targets for cadmium in
      hepatocytes, we have studied the effects of CdCl2 on the hybrid cell line WIF-B9
      that exhibits stable structural and functional hepatocytic polarity. RESULTS: We
      showed that the toxicity of CdCl2 (1 uM, 24 h) resulted in a reduction in direct
      intercellular communication (via gap junctions) and in an increase in
      paracellular permeability (decrease in the sealing of tight junctions). These
      effects were not related to changes in the expression of the key proteins
      involved, Cx32 and claudin 2, the first being constitutive of gap junctions and
      the second of tight junctions in this cell line. Using immunofluorescence
      experiments, we observed a change in the location of Cx32 and claudin 2: these
      two proteins were less often found in the tight junction network that closes the
      bile canaliculi (BC). In control cells, 'Proximity Ligation Assay' (PLA
      Duolink(r)) has confirmed in situ that molecules of claudin 2 and Cx32 are very
      close to each other at the BC (probably less than 16 nm). This was no longer the
      case after treatment with CdCl2 . Localisation of occludin and Cx32 relative to
      each other was not modified by CdCl2 , but CdCl2 increased the PLA signal between
      molecules of JAM-A and Cx32. Finally, examination of freeze-fracture replicas
      obtained from cultures treated with CdCl2 showed the disruption of the network of
      tight junctions and the depletion or the disintegration of the junctional plaques
      associated with tight junctions. CONCLUSIONS: This study demonstrates in situ the
      changes induced by cadmium on the organisation of cell-cell junctions and points
      out the importance of the association Cx32/claudin 2 for the maintenance of
      normal hepatocyte functions.

PMID- 24117458
TI  - G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role
      in the antinociceptive effect of oxycodone, but not morphine, at supraspinal
      sites.
AB  - BACKGROUND AND PURPOSE: Oxycodone and morphine are MU-opioid receptor agonists
      prescribed to control moderate-to-severe pain. Previous studies suggested that
      these opioids exhibit different analgesic profiles. We hypothesized that distinct
      mechanisms mediate the differential effects of these two opioids and investigated
      the role of G protein-gated inwardly rectifying potassium (K(IR)3 also known as
      GIRK) channels in their antinociceptive effects. EXPERIMENTAL APPROACH: Opioid
      induced antinociceptive effects were assessed in mice, using the tail-flick test,
      by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone
      and following inhibition of K(IR)3.1 channels with tertiapin-Q (30 pmol per
      mouse, i.c.v. and i.t.) and K(IR)3.1-specific siRNA. The antinociceptive effects
      of oxycodone and morphine were also examined after tertiapin-Q administration in
      the mouse femur bone cancer and neuropathic pain models. KEY RESULTS: The
      antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations,
      were markedly attenuated by K(IR)3.1 channel inhibition. In contrast, the
      antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced
      by i.t. morphine were attenuated, by K(IR)3.1 channel inhibition. In the two
      chronic pain models, the antinociceptive effects of s.c. oxycodone, but not
      morphine, were inhibited by supraspinal administration of tertiapin-Q. CONCLUSION
      AND IMPLICATIONS: These results demonstrate that K(IR)3.1 channels play a primary
      role in the antinociceptive effects of oxycodone, but not those of morphine, at
      supraspinal sites and suggest that supraspinal K(IR)3.1 channels are responsible
      for the unique analgesic profile of oxycodone.

PMID- 24117460
TI  - On the Formation of Thymine Photodimers in Thymine Single Strands and Calf Thymus
      DNA.
AB  - Solar light leads to thymine dimers that are mutagenic and primary cause of skin
      cancer. Here, we report absorption and synchrotron radiation circular dichroism
      (CD) spectra of Tn single strands with different number n of bases (n = 2-7, 10,
      11) recorded after various 254 nm irradiation times. From a principal component
      analysis of the CD spectra, we extract fingerprint spectra of both the
      cyclobutane pyrimidine dimer (CPD) and the pyrimidine (6-4) pyrimidone
      photoadduct (64PP). Extending the CD measurements to the vacuum ultraviolet
      region in combination with systematic examinations of size effects is a new
      approach to gain insight on the dimeric photoproducts. We find a simple linear
      correlation between n and average number of dimers formed after 1 h of
      irradiation. The probability for a thymine to engage in a dimer increases from
      32% for n = 2 to 41% for n = 11, which implies limited effects of terminal
      thymines, i.e., the reaction does not occur preferentially at the extremities of
      the single strands as previously stated. It is even possible to form two dimers
      with only two bridging thymines. Finally, experiments conducted on calf thymus
      DNA provided a similar signature of the photodimer, but differences are also
      evident.

PMID- 24117461
TI  - Latent fingerprint visualization using a scanning Kelvin probe in conjunction
      with vacuum metal deposition.
AB  - The application of vacuum metal deposition before scanning Kelvin probe
      visualization of fingerprints is investigated. The potential contrast between
      fingerprint ridges and furrows is maximized by the use of silver deposition for
      non-noble metals and gold-zinc deposition for noble metals. The higher
      susceptibility of eccrine fingerprints to vacuum metal overdeposition is
      confirmed. Additionally, fingerprints are best developed individually and by
      building the metal deposition slowly to protect against overdevelopment and
      variation in the rate of metal condensation. The progress of the metal deposition
      can be monitored using the scanning Kelvin probe by reference to the change in
      potential and continuity of the new potential on the surface. The use of acetic
      acid solution for the recovery of overVMD-developed samples is shown not to be
      useful. Applying the metal deposition has the additional prospect of increasing
      surface conductivity and homogeneity and both can aid fingerprint visualization
      using the scanning Kelvin probe. 

PMID- 24117462
TI  - Components in soy allergy diagnostics: Gly m 2S albumin has the best diagnostic
      value in adults.
AB  - BACKGROUND: Thus far, four soy allergens have been characterized. Their
      diagnostic value was assessed only using a case-control design with controls not
      suspected of soy allergy or in a soy-allergic population without controls. Our
      objective was to analyze the diagnostic value of specific immunoglobulin E (sIgE)
      to Gly m 2S albumin, Gly m 4, 5, and 6, and their possible relation with severity
      or culprit soy product. METHODS: Adult patients suspected of soy allergy were
      included (n = 46). Allergy was confirmed by challenge (n = 19) or history (n =
      16) and excluded by challenge in 11 patients. Soy components were analyzed by
      ImmunoCAP. Diagnostic value was assessed in the challenged patient group by an
      area under receiver operating characteristic (ROC) curve (AUC). RESULTS: Specific
      immunoglobulin E to Gly m 2S albumin had the highest AUC (0.79), comparable to
      skin prick test (SPT) and sIgE to soy extract (0.76 and 0.77, respectively). All
      patients were sensitized to either soy extract or Gly m 4 (sIgE >= 0.35 kU/l).
      sIgE to soy extract, Gly m 5, and Gly m 6 was significantly higher in patients
      with mild symptoms (P = 0.04, 0.02 and 0.02, respectively). Patients only
      reacting to soy milk had higher sIgE levels to Gly m 4 (median 9.8 vs 1.1 kU/l, P
      = 0.01). CONCLUSION: Specific immunoglobulin E to Gly m 2S albumin had the best
      accuracy in diagnosing soy allergy. Gly m 5 and 6 were related to mild symptoms.
      Higher levels of Gly m 4 were related to allergy to soy milk.

PMID- 24117463
TI  - Dichotic listening, executive functions and grey matter cortical volume in
      patients with schizophrenia and healthy controls.
AB  - Schizophrenia is characterized by cognitive impairment, especially in relation to
      executive functions. Brain structural abnormalities are also often seen in
      schizophrenia although little is known of the relationship between cognitive
      impairment and structural brain changes. Our aim was therefore to investigate
      this relationship further using MRI and a dichotic listening (DL) task with
      simple speech sounds and with instructions to focus attention and report only
      from the left or right ear stimulus. When instructed to focus attention on the
      left ear syllable a cognitive conflict is induced requiring the allocation of
      executive resources to be resolved. Grey matter (GM) volume was measured with MRI
      from four volumes of interests (VOIs), left and right frontal and temporal
      cortex, respectively, and correlated with DL performance. The results showed
      significant differences between the groups in their ability to focus attention on
      and report the left ear stimulus, which was accompanied by reduced GM volume in
      the left frontal and right temporal lobe VOIs. There was also a significant
      positive correlation between left frontal GM volume and performance on the DL
      task, for the groups combined. The results did not support a conclusion that an
      impairment in cognitive function in schizophrenia was driven by an corresponding
      impairment in brain structure, since there were no significant correlations when
      the groups were analyzed separately. It is however concluded that patients with
      schizophrenia are impaired in executive functions and that they also show reduced
      GM volumes in left frontal and right temporal lobe areas, compared to healthy
      controls. 

PMID- 24117465
TI  - Translational research in practice.
AB  - Readers will now be familiar with the notion of 'translational research'.
      According to its generally acknowledged progenitor, the National Institutes of
      Health (NIH) in the US, this is a kind of research agenda focused on translating
      or applying the research findings from basic/preclinical studies to human studies
      and perhaps most especially treatment trials; and, the translation of clinical
      research findings to the community so that evidence-based best practice is
      adopted. 

PMID- 24117464
TI  - Treatment of refractory thrombotic thrombocytopenic purpura with N
      acetylcysteine: a case report.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening
      disease resulting in systemic microvascular thrombosis. The disease is caused by
      excessive platelet (PLT) adhesion to ultra-large (UL) von Willebrand factor (VWF)
      multimers inadequately cleaved by the processing enzyme ADAMTS-13. While many
      cases respond to plasma exchange performed with or without concurrent
      corticosteroids, treatment of the 10% to 20% of patients with refractory disease
      is difficult. Experimental studies demonstrating that N-acetylcysteine (NAC)
      inhibits PLT binding to endothelial cell-secreted and anchored UL VWF multimers
      suggest that NAC may be useful in the treatment of TTP. CASE REPORT: A 44-year
      old woman presented with malaise, confusion, chest and abdominal pain, and
      transient visual loss. Laboratory results and peripheral blood smear were
      consistent with TTP. The patient was begun on plasma exchange and corticosteroid
      treatment, but after 10 days the PLT count was still less than 10.0 * 10(9) /L
      and she developed a fever. Rituximab was initiated, but the patient's condition
      worsened and she became comatose. Antibiotics were initiated, but cultures
      remained sterile. After 3 days of coma and further clinical deterioration,
      treatment with NAC was begun. The patient received a loading dose of 150 mg/kg
      NAC intravenously (IV) over 1 hour. Within 18 hours the patient awakened abruptly
      and began communicating with medical personnel. Plasma exchange, corticosteroids,
      rituximab, and NAC infusion (150 mg/kg IV over 17 hr daily * 10 days) were
      continued and by Day 17 the PLT count was more than 50 * 10(9) /L. The patient
      fully recovered and was discharged on Day 31. CONCLUSION: This is the first
      complete report of a TTP patient treated with NAC. NAC was a safe and effective
      supplementary treatment for refractory TTP in this patient.

PMID- 24117466
TI  - Genetic constraints underlying human reproductive timing in a premodern Swiss
      village.
AB  - The trade-off between reproductive investment in early versus late life is
      central to life-history theory. Despite abundant empirical evidence supporting
      different versions of this trade-off, the specific trade-off between age at first
      reproduction (AFR) and age at last reproduction (ALR) has received little
      attention, especially in long-lived species with a pronounced reproductive
      senescence such as humans. Using genealogical data for a 19th-century Swiss
      village, we (i) quantify natural selection acting on reproductive timing, (ii)
      estimate the underlying additive genetic (co)variances, and (iii) use these to
      predict evolutionary responses. Selection gradients were computed using multiple
      linear regression, and the additive genetic variance-covariance matrix was
      estimated using a restricted maximum-likelihood animal model. We found strong
      selection for both an early AFR and a late ALR, which resulted from selection for
      an earlier and longer reproductive period (RP, i.e., ALR-AFR). Furthermore,
      postponing AFR shortened RP in both sexes, but twice as much in women. Finally,
      AFR and ALR were strongly and positively genetically correlated, which led to a
      considerable reduction in the predicted responses to selection, or even rendered
      them maladaptive. These results provide evidence for strong genetic constraints
      underlying reproductive timing in humans, which may have contributed to the
      evolution of menopause. 

PMID- 24117467
TI  - MetalS2: a tool for the structural alignment of minimal functional sites in metal
      binding proteins and nucleic acids.
AB  - We developed a new software tool, MetalS(2), for the structural alignment of
      Minimal Functional Sites (MFSs) in metal-binding biological macromolecules. MFSs
      are 3D templates that describe the local environment around the metal(s)
      independently of the larger context of the macromolecular structure. Such local
      environment has a determinant role in tuning the chemical reactivity of the
      metal, ultimately contributing to the functional properties of the whole system.
      On our example data sets, MetalS(2) unveiled structural similarities that other
      programs for protein structure comparison do not consistently point out and
      overall identified a larger number of structurally similar MFSs. MetalS(2)
      supports the comparison of MFSs harboring different metals and/or with different
      nuclearity and is available both as a stand-alone program and a Web tool (
      http://metalweb.cerm.unifi.it/tools/metals2/).

PMID- 24117468
TI  - A brief, critical review of research on impaired control over alcohol use and
      suggestions for future studies.
AB  - Impaired control, defined as "a breakdown of an intention to limit consumption"
      (Heather et al. J Stud Alcohol 1993; 54, 701), has historically been considered
      an important aspect of addiction. Despite recognition of its importance to
      addiction and potential value as an early indicator of problem drinking risk, we
      argue that impaired control over alcohol use has not received sufficient research
      attention. In an effort to spark further research, the present critical review
      offers brief discussion of the current state of knowledge regarding impaired
      control and avenues for future research. Three main research areas are addressed:
      (i) epidemiology; (ii) measurement issues; and (iii) potential mechanisms
      underlying relationships between impaired control and subsequent problem
      drinking. Measurement issues include complexities involved in self-report
      assessment of impaired control, development and validation of human and animal
      laboratory models, and impaired control's relationship to other constructs (i.e.,
      impulsivity and other difficulties with self-control; symptoms of dependence such
      as craving). We discuss briefly 2 potential mechanisms that may help to explain
      why some drinkers experience impaired control while others do not:
      neurobiological dysfunction and family history/genetics. Suggestions for future
      research are focused on ways in which the impaired control construct may enhance
      prediction of who might be at particular risk of subsequent problem drinking and
      to facilitate intervention to reduce problem alcohol use. 

PMID- 24117469
TI  - GABA(A) receptor transmembrane amino acids are critical for alcohol action:
      disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative
      location of binding sites.
AB  - Alcohols and inhaled anesthetics modulate GABA(A) receptor (GABA(A)R) function
      via putative binding sites within the transmembrane regions. The relative
      position of the amino acids lining these sites could be either inter- or intra
      subunit. We introduced cysteines in relevant TM locations and tested the
      proximity of cysteine pairs using oxidizing and reducing agents to induce or
      break disulfide bridges between cysteines, and thus change GABA-mediated currents
      in wild-type and mutant alpha1beta2gamma2 GABA(A)Rs expressed in Xenopus laevis
      oocytes. We tested for: (i) inter-subunit cross-linking: a cysteine located in
      alpha1TM1 [either alpha1(Q229C) or alpha1(L232C)] was paired with a cysteine in
      different positions of beta2TM2 and TM3; (ii) intra-subunit cross-linking: a
      cysteine located either in beta2TM1 [beta2(T225C)] or in TM2 [beta2(N265C)] was
      paired with a cysteine in different locations along beta2TM3. Three inter-subunit
      cysteine pairs and four intra-subunits cross-linked. In three intra-subunit
      cysteine combinations, the alcohol effect was reduced by oxidizing agents,
      suggesting intra-subunit alcohol binding. We conclude that the structure of the
      alcohol binding site changes during activation and that potentiation or
      inhibition by binding at inter- or intra-subunit sites is determined by the
      specific receptor and ligand.

PMID- 24117470
TI  - Crossover rate between homologous chromosomes and interference are regulated by
      the addition of specific unpaired chromosomes in Brassica.
AB  - Recombination is a major mechanism generating genetic diversity, but the control
      of the crossover rate remains a key question. In Brassica napus (AACC, 2n = 38),
      we can increase the homologous recombination between A genomes in AAC hybrids.
      Hypotheses for this effect include the number of C univalent chromosomes, the
      ratio between univalents and bivalents and, finally, which of the chromosomes are
      univalents. To test these hypotheses, we produced AA hybrids with zero, one,
      three, six or nine additional C chromosomes and four different hybrids carrying
      2n = 32 and 2n = 35 chromosomes. The genetic map lengths for each hybrid were
      established to compare their recombination rates. The rates were 1.4 and 2.7
      times higher in the hybrids having C6 or C9 alone than in the control (0C). This
      enhancement reached 3.1 and 4.1 times in hybrids carrying six and nine C
      chromosomes, and it was also higher for each pair of hybrids carrying 2n = 32 or
      2n = 35 chromosomes, with a dependence on which chromosomes remained as
      univalents. We have shown, for the first time, that the presence of one
      chromosome, C9 , affects significantly the recombination rate and reduces
      crossover interference. This result will have fundamental implications on the
      regulation of crossover frequency.

PMID- 24117471
TI  - Review article: newer optical and digital chromoendoscopy techniques vs. dye
      based chromoendoscopy for diagnosis and surveillance in inflammatory bowel
      disease.
AB  - BACKGROUND: Recent innovations in gastrointestinal endoscopy have changed our
      traditional approach to diagnosis and therapy in patients with inflammatory bowel
      diseases (IBD). While traditionally used dye-based chromoendoscopy (DBC)
      techniques suffer from several limitations that reduce their utility in daily
      routine practice, newer 'dye-less' chromoendoscopy (DLC) techniques offer a great
      potential to overcome most of these limitations. AIM: To review available optical
      and digital chromoendoscopy techniques, by critically discussing their potential
      for diagnostic and surveillance colonoscopy in patients with IBD. METHODS: A
      literature search on the use of dye-less and dye-based chromoendoscopy in IBD
      patients was performed. RESULTS: In long-standing IBD, DBC improves detection of
      dysplasia (diagnostic odds ratio = 17.5, 95% CI = 1.2-247.1) as well as
      prediction of inflammatory disease activity and extent of disease compared with
      standard video-colonoscopy. Narrow band imaging (NBI) shows no improvement in
      dysplasia detection rates compared with white-light endoscopy and DBC (P = 0.6).
      Moreover, NBI results in a suboptimal differentiation of dysplastic from
      nondysplastic lesions. No data regarding digital DLC techniques (i.e. FICE, i
      scan) for dysplasia detection in IBD are yet available. Both NBI and i-scan are
      superior to white-light endoscopy in assessing the activity and extent of
      colorectal IBD. CONCLUSIONS: Although the potential benefits of newer optical and
      digital dye-less chromoendoscopy techniques over traditionally used DBC are
      substantial, only DBC can currently be recommended to improve dysplasia detection
      in long-standing IBD. In contrast, DLC has the potential to quantify disease
      activity and mucosal healing in IBD.

PMID- 24117473
TI  - Use of optimized aminotransferase methods in regulated preclinical studies.
AB  - BACKGROUND: The serum activities of ALT and AST are key indicators of liver
      toxicity in the drug safety evaluation of laboratory animals and patients. To
      ensure that the full aminotransferase activity is measured, exogenous Pyridoxyl-5
      Phosphate (P5P) cofactor is included in the assay reagent. Clinical pathology
      laboratories make a choice to use aminotransferase assays with or without the
      added P5P cofactor, and the impact of assay selection on safety assessment is not
      well understood. OBJECTIVES: The objective of this report was to investigate the
      effect of aminotransferase assay selection on the detection of liver toxicity
      based on a literature review. METHODS: Literature in public databases was
      searched using combinations of the search terms alanine aminotransferase,
      aspartate aminotransferase, pyridoxyl-5-phosphate, holoenzyme, apoenzyme, enzyme
      inhibition, artifact, clinical pathology, toxicology, and safety assessment.
      Regulations or guidance documents published by health authorities specifying
      clinical pathology evaluation in nonclinical and clinical safety studies of
      biopharmaceuticals, chemicals, and devices were also reviewed. RESULTS:
      Aminotransferase testing is not standardized in safety assessment studies and
      consequently, laboratories use aminotransferase assays with or without P5P
      cofactor. Individual studies have demonstrated mean differences of approximately
      10-20% in serum ALT activity in animal and human populations. The impact of
      aminotransferase testing without P5P on detection of toxicity and decision-making
      in drug development has not been systematically evaluated. CONCLUSIONS: The use
      of different assays for measuring aminotransferase activity contributes to the
      variability in data between laboratories and studies. Standardizing
      aminotransferase assays is an avenue for improving the diagnostic performance in
      drug safety evaluation.

PMID- 24117472
TI  - Preconception biomarkers of allostatic load and racial disparities in adverse
      birth outcomes: the Bogalusa Heart Study.
AB  - BACKGROUND: Large disparities in adverse birth outcomes persist between African
      American and white women in the US despite decades of research, policy, and
      public health intervention. Allostatic load is an index of dysregulation across
      multiple physiologic systems that results from chronic exposure to stress in the
      physical and socio-cultural environment which may lead to earlier health
      deterioration among racially or socio-economically disadvantaged groups. The
      purpose of this investigation was to examine relationships between maternal
      biomarkers of allostatic load prior to conception and the occurrence of preterm
      birth and small for gestational age infants among a cohort of white and African
      American women participants in the Bogalusa Heart Study. METHODS: Data from women
      participants were linked to the birth record of their first-born infant.
      Principal components analysis was used to construct an index of allostatic load
      as a summary of the weighted contribution of nine biomarkers representing three
      physiologic domains: cardiovascular, metabolic, and immune systems. A series of
      Poisson regression models based on samples ranging from 1467 to 375 women were
      used to examine race, individual biomarkers of allostatic load, and quartiles of
      the allostatic load index as predictors of preterm birth (n = 150, 10.2%) and
      small for gestational age (n = 135, 9.2%). RESULTS: There was no evidence of a
      relationship between maternal preconception allostatic load and either adverse
      birth outcome in this sample. Further, there was no evidence of effect
      modification of by race or education. CONCLUSIONS: More work is needed in
      understanding the biological mechanisms linking social inequities to racial
      disparities in adverse birth outcomes.

PMID- 24117474
TI  - Cerebral functional asymmetry and phonological performance in dyslexic adults.
AB  - Developmental dyslexia is a frequent language-based learning disorder
      characterized by difficulty in reading. The predominant etiologic view postulates
      that reading impairment is related to phonological and orthographic dysfunction.
      The aim of this fMRI study was to evaluate the neural bases of phonological
      processing impairment in remediated dyslexic adults (DD). We used a rhyming words
      judgment task contrasted with an unreadable fonts font-matching judgment task to
      compare patterns of activation and functional asymmetry in DD and normal-reading
      young adults. We found evidence of a link between asymmetry in inferior frontal
      gyrus and performance during the phonological processing. We also observed that
      DD recruit a network including regions involved in articulatory control in order
      to achieve rhyme judgment suggesting that, due to a lack of hemispheric
      specialization, DD recruit the latter network to achieve rhyme judgment. 

PMID- 24117475
TI  - Cholangioma in the Mozambique tilapia, Oreochromis mossambicus (Peters).

PMID- 24117477
TI  - Photohemolysis Sensitized by the Furocoumarin Derivative Alloimperatorin and its
      Hydroperoxide Photooxidation Product.
AB  - The dark and photosensitized effects of alloimperatorin methyl ether 1 (hereafter
      simply alloimperatorin) and its photooxygenation product alloimperatorin
      hydroperoxide 2 were investigated on human erythrocytes. The results reveal that
      the furocoumarin 1 photosensitizes efficiently the hemolysis of erythrocytes. The
      rate of photohemolysis increases on raising the temperature of the postirradiated
      incubation from 4 degrees C to 37 degrees C. Thermal activation of the
      photohemolysis and inhibition by 2,6-di-tert-butyl-p-cresol (BHT) suggest that
      the furocoumarin 1 photosensitizes lipid peroxidation, increasing permeability in
      the erythrocyte membrane. The hydroperoxide 2 induces dark and photosensitized
      hemolysis more efficiently than the furocoumarin 1. The rate of hemolysis induced
      by 2 increases with the incubation temperature and decreases in the presence of
      tert-butanol and BHT. The hydroperoxide 2 photosensitizes the formation of lipid
      peroxidation products as shown by the reaction with thiobarbituric acid. This
      process is diminished by BHT. Our data imply that the photohemolysis sensitized
      by the furocoumarin 1 is caused by the in situ-formed photooxygenation product 2.
      Such hydroperoxides are potent hemolytic agents in the dark and especially on
      photosensitization.

PMID- 24117476
TI  - Asymmetrical effects of mesophyll conductance on fundamental photosynthetic
      parameters and their relationships estimated from leaf gas exchange measurements.
AB  - Worldwide measurements of nearly 130 C3 species covering all major plant
      functional types are analysed in conjunction with model simulations to determine
      the effects of mesophyll conductance (g(m)) on photosynthetic parameters and
      their relationships estimated from A/Ci curves. We find that an assumption of
      infinite g(m) results in up to 75% underestimation for maximum carboxylation rate
      V(cmax), 60% for maximum electron transport rate J(max), and 40% for triose
      phosphate utilization rate T(u) . V(cmax) is most sensitive, J(max) is less
      sensitive, and T(u) has the least sensitivity to the variation of g(m). Because
      of this asymmetrical effect of g(m), the ratios of J(max) to V(cmax), T(u) to
      V(cmax) and T(u) to J(max) are all overestimated. An infinite g(m) assumption
      also limits the freedom of variation of estimated parameters and artificially
      constrains parameter relationships to stronger shapes. These findings suggest the
      importance of quantifying g(m) for understanding in situ photosynthetic machinery
      functioning. We show that a nonzero resistance to CO2 movement in chloroplasts
      has small effects on estimated parameters. A non-linear function with gm as input
      is developed to convert the parameters estimated under an assumption of infinite
      gm to proper values. This function will facilitate gm representation in global
      carbon cycle models.

PMID- 24117478
TI  - The role of ultrasound findings in the management of thyroid nodules with atypia
      or follicular lesions of undetermined significance.
AB  - BACKGROUND: Atypia or follicular lesions of undetermined significance (AUS/FLUS)
      is a broad cytological category in the Bethesda system for classifying thyroid
      cytology. This study investigated the diagnostic accuracy of ultrasound (US)
      analysis of thyroid nodules with AUS/FLUS. PATIENTS AND METHODS: Of 5062 subjects
      with nodules subjected to fine-needle aspiration cytology (FNACs) at our
      institution from January 2010 through May 2012, 383 met the Bethesda criteria for
      AUS/FLUS. After excluding subjects who had a history of thyroid cancer, who only
      underwent repeat FNA or who underwent no further examinations, we selected 249
      subjects who had subsequently undergone a core-needle biopsy and/or surgery. Of
      these, 100 were found to have malignant nodules (40.2%), 122 had benign nodules
      (49%), and 27 had nodules with indeterminate status (10.8%). We compared specific
      US parameters, including size, location, content, shape, margin, echogenicity,
      echotexture and calcification across these subject groups. RESULTS: Multivariate
      analysis revealed that malignancy was associated with taller-than-wide shape
      (TDW) (OR = 8.43, P = 0.002), ill-defined margin (OR = 3.23, P = 0.002) and
      marked hypoechogenicity. (OR = 3.61, P = 0.001). The specificity and positive
      predictive values of TDW were 98% and 90.6%,respectively. The specificity and
      positive predictive values of 'TDW and marked hypoechogenicity' were both 100%.
      CONCLUSION: US findings play a complementary role in the diagnosis of thyroid
      nodules with AUS/FLUS. In case of highly suspicious US findings such as 'TDW and
      marked hypoechogenicity', could be very helpful in the diagnosis of malignancy.

PMID- 24117479
TI  - Hope grounded in belief: Influences of reward for application and social cynicism
      on dispositional hope.
AB  - Two studies explore whether general beliefs about the social world or social
      axioms may be antecedents of dispositional hope. Social axioms are generalized
      cognitive representations that provide frames for constructing individuals' hope
      related cognitions. Considering social axioms' instrumental and ego-defensive
      functions, two social axioms, social cynicism and reward for application are
      hypothesized to be negative and positive predictors of hope, respectively. Study
      1 used multiple regression analysis to test the hypothesis. Study 2 used
      structural equation modeling to test the model with a pathway linking reward for
      application with hope, and another pathway linking social cynicism and hope that
      is mediated by self-esteem. The results are discussed in terms of extending the
      range of psychological constructs and processes that foster the development of
      hope. 

PMID- 24117480
TI  - Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology
      observed in streptozotocin-induced Alzheimer's disease.
AB  - OBJECTIVES: Adults who develop type 2 diabetes (T2D) at later stages are at a
      higher risk of developing Alzheimer's disease (AD). Pharmacological agents such
      as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon
      like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates
      as disease-modifying agents in the treatment of AD. The present study
      investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin
      (STZ)-induced rat model of AD. METHODS: Three months following the induction of
      AD by intracerebral injection of STZ, animals were orally administered with
      vildagliptin (2.5, 5 and 10 mg/kg) for 30 days. Dose-dependent and time-course
      effects of vildagliptin on memory retention were investigated during the course
      of treatment. Following treatment, the animals were sacrificed, and brain tissues
      were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP
      1 levels, amyloid beta (Abeta) burden, tau phosphorylation and inflammatory
      markers. KEY FINDINGS: The results reveal a time-dependent improvement in memory
      retention and a dose-dependent attenuation of Abeta, tau phosphorylation and
      inflammatory markers and increased GLP-1 levels. CONCLUSIONS: These robust
      therapeutic effects of vildagliptin demonstrate a unique mechanism for Abeta and
      tau clearance and reverse the cognitive deficits and pathology observed in AD.

PMID- 24117481
TI  - Does bleeding affect patient-reported outcome measures in patients with
      myelodysplasia or hematologic malignancies: a systematic review.
AB  - BACKGROUND: Relatively minor bleeding (e.g., bruising and/or petechiae) may cause
      patient distress. This systematic review's objective was to assess whether
      bleeding affects health-related quality of life (HRQoL) or illness perceptions or
      representations (IPs) in patients with hematologic malignancies or myelodysplasia
      (MDS). STUDY DESIGN AND METHODS: We searched, in full, 12 electronic databases
      (including CENTRAL, MEDLINE, and EMBASE) up to January 7, 2013, for eligible
      randomized controlled trials (RCTs), prospective cohort studies, and cross
      sectional studies. RESULTS: A total of 6247 studies were initially identified;
      5945 studies were excluded on the basis of the abstract. A total of 302 full-text
      articles were evaluated independently by two reviewers; of these, six studies
      within seven citations were eligible for inclusion. Two studies are still in
      progress, four studies within five citations were included in this review (one
      RCT, one prospective observational study, one interview study, and one Web-based
      survey). None of the included studies were designed to assess the impact bleeding
      had on HRQoL or IPs. The Web-based survey and observational study used two new
      patient-reported outcome scales which specifically assessed patient distress or
      concern due to bleeding. The majority of patients within these two studies either
      did not experience bleeding or did not have severe thrombocytopenia. CONCLUSION:
      There is insufficient evidence to demonstrate whether bleeding is a significant
      clinical problem that affects patients' HRQoL or IPs in either patients with MDS
      or patients with hematologic malignancies. Rigorously designed studies to assess
      the scale of this problem in both of these groups of patients are required.

PMID- 24117482
TI  - Characteristics of heart rate variability in alcohol-dependent subjects and
      nondependent chronic alcohol users.
AB  - Heart rate variability (HRV) is an objective and sensitive measure of integrated
      physiological functioning reflective of heart rhythm responsivity to internal and
      external demands. Reduced HRV is associated with vulnerability to stress and
      deterioration of medical and/or psychiatric conditions, while increased HRV is
      associated with a favorable treatment response and recovery from various medical
      and/or psychiatric conditions. Our previous review found that acute alcohol
      consumption caused decreased parasympathetic and increased sympathetic HRV
      effects in both nonalcoholic and chronic alcohol users. This review investigates
      the effects of chronic alcohol consumption on HRV in alcohol-dependent subjects
      and nondependent users. MEDLINE, Scopus, and PubMed were searched for human
      experimental and clinical trials that measured the effects of chronic alcohol use
      on HRV. Only publications that included a description of their study designs and
      clearly stated methodologies for data collections, and outcome measures were
      reviewed. We have reviewed a total of 24 articles. In nondependent users, low
      dose (approximating the recommended daily amount of 1 standard drink in women and
      2 in men) use is associated with increased HRV parameters compared to those who
      drink less frequently or abstain altogether. A further increase in consumption is
      associated with decreased HRV compared to both abstainers and more moderate
      drinkers. HRV changes during withdrawal generally follow the same negative
      direction but are more complex and less understood. In dependent subjects, an
      improvement in HRV was seen following abstinence but remained reduced compared to
      nonalcoholic controls. This review demonstrates that HRV changes associated with
      chronic use follow a J-shaped curve. It supports recommendations that limit daily
      alcohol intake to no more than 2 drinks for men and 1 drink for women. Future
      studies should investigate HRV as a biomarker of alcoholism development and
      treatment response as well as the physiological basis for alcohol effects on HRV.

PMID- 24117483
TI  - Comorbidities in preschool children at family risk of dyslexia.
AB  - BACKGROUND: Comorbidity among developmental disorders such as dyslexia, language
      impairment, attention deficit/hyperactivity disorder and developmental
      coordination disorder is common. This study explores comorbid weaknesses in
      preschool children at family risk of dyslexia with and without language
      impairment and considers the role that comorbidity plays in determining
      children's outcomes. METHOD: The preschool attention, executive function and
      motor skills of 112 children at family risk for dyslexia, 29 of whom also met
      criteria for language impairment, were assessed at ages 31/2 and 41/2 years. The
      performance of these children was compared to the performance of children with
      language impairment and typically developing controls. RESULTS: Weaknesses in
      attention, executive function and motor skills were associated with language
      impairment rather than family risk status. Individual differences in language and
      executive function are strongly related during the preschool period, and
      preschool motor skills predicted unique variance (4%) in early reading skills
      over and above children's language ability. CONCLUSION: Comorbidity between
      developmental disorders can be observed in the preschool years: children with
      language impairment have significant and persistent weaknesses in motor skills
      and executive function compared to those without language impairment. Children's
      early language and motor skills are predictors of children's later reading
      skills.

PMID- 24117484
TI  - Classification and practical approach to the diagnosis and management of
      hypersensitivity to nonsteroidal anti-inflammatory drugs.
AB  - Hypersensitivity reactions to aspirin (acetylsalicylic acid) and other
      nonsteroidal anti-inflammatory drugs (NSAIDs) constitute only a subset of all
      adverse reactions to these drugs, but due to their severity pose a significant
      burden to patients and are a challenge to the allergist. In susceptible
      individuals, NSAIDs induce a wide spectrum of hypersensitivity reactions with
      various timing, organ manifestations, and severity, involving either
      immunological (allergic) or nonimmunological mechanisms. Proper classification of
      reactions based on clinical manifestations and suspected mechanism is a
      prerequisite for the implementation of rational diagnostic procedures and
      adequate patient management. This document, prepared by a panel of experts from
      the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs
      Hypersensitivity, aims at reviewing the current knowledge in the field and
      proposes uniform definitions and clinically useful classification of
      hypersensitivity reactions to NSAIDs. The document proposes also practical
      algorithms for the diagnosis of specific types of NSAIDs hypersensitivity (which
      include drug provocations, skin testing and in vitro testing) and provides, when
      data are available, evidence-based recommendations for the management of
      hypersensitive patients, including drug avoidance and drug desensitization. 

PMID- 24117485
TI  - Corneal nerve fibre damage precedes diabetic retinopathy in patients with type 2
      diabetes mellitus.
AB  - AIMS: To quantify the morphological alterations in corneal nerve fibres and cells
      in patients with type 2 diabetes mellitus in relation to the severity of diabetic
      retinopathy. METHODS: One hundred and thirty-two eyes of 132 patients with type 2
      diabetes and 32 eyes of 32 healthy control subjects were evaluated with in vivo
      corneal confocal microscopy. Patients with diabetes were classified into three
      groups: patients without diabetic retinopathy, patients with non-proliferative
      diabetic retinopathy and patients with proliferative diabetic retinopathy.
      Anterior and posterior stromal keratocyte, endothelial cell and basal epithelial
      cell densities and sub-basal nerve fibre structure were evaluated. RESULTS:
      Significant reductions in basal epithelial cell, anterior stromal keratocyte and
      endothelial cell densities were observed only in patients with diabetic
      retinopathy. However, nerve fibre density, nerve branch density and nerve fibre
      length were reduced in patients without diabetic retinopathy and worsened
      progressively with increasing severity of retinopathy. CONCLUSIONS: Corneal cell
      pathology occurs in patients with diabetic retinopathy, but corneal nerve fibre
      damage seems to precede the development of diabetic retinopathy.

PMID- 24117486
TI  - Loss of FUBP1 expression in gliomas predicts FUBP1 mutation and is associated
      with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of
      heterozygosity.
AB  - AIMS: The Far Upstream Element [FUSE] Binding Protein 1 (FUBP1) regulates target
      genes, such as the cell cycle regulators MYC and p21. FUBP1 is up-regulated in
      many tumours and acts as an oncoprotein by stimulating proliferation and
      inhibiting apoptosis. Recently, FUBP1 mutations were identified in approximately
      15% of oligodendrogliomas. To date, all reported FUBP1 mutations have been
      predicted to inactivate FUBP1, which suggests that in contrast to most other
      tumours FUBP1 may act as a tumour suppressor in oligodendrogliomas. METHODS: As
      no data are currently available concerning FUBP1 protein levels in gliomas, we
      examined the FUBP1 expression profiles of human glial tumours by
      immunohistochemistry and immunofluorescence. We analysed FUBP1 expression related
      to morphological differentiation, IDH1 and FUBP1 mutation status, 1p/19q loss of
      heterozygosity (LOH) as well as proliferation rate. RESULTS: Our findings
      demonstrate that FUBP1 expression levels are increased in all glioma subtypes as
      compared with normal central nervous system (CNS) control tissue and are
      associated with increased proliferation. In contrast, FUBP1 immunonegativity
      predicted FUBP1 mutation with a sensitivity of 100% and a specificity of 90% in
      our cohort and was associated with oligodendroglial differentiation, IDH1
      mutation and 1p/19q loss of heterozygosity (LOH). Using this approach, we
      detected a to-date undescribed FUBP1 mutation in an oligodendroglioma.
      CONCLUSION: In summary, our data indicate an association between of FUBP1
      expression and proliferation in gliomas. Furthermore, our findings present FUBP1
      immunohistochemical analysis as a helpful additional tool for neuropathological
      glioma diagnostics predicting FUBP1 mutation.

PMID- 24117487
TI  - Relationship between plasma, atrial and ventricular perhexiline concentrations in
      humans: insights into factors affecting myocardial uptake.
AB  - AIM: Little is known regarding the steady-state uptake of drugs into the human
      myocardium. Perhexiline is a prophylactic anti-anginal drug which is increasingly
      also used in the treatment of heart failure and hypertrophic cardiomyopathy. We
      explored the relationship between plasma perhexiline concentrations and its
      uptake into the myocardium. METHODS: Blood, right atrium +/- left ventricle
      biopsies were obtained from patients treated with perhexiline for a median of 8.5
      days before undergoing coronary surgery in the perhexiline arm of a randomized
      controlled trial. Perhexiline concentrations in plasma and heart tissue were
      determined by HPLC. RESULTS: Atrial biopsies were obtained from 94 patients and
      ventricular biopsies from 28 patients. The median plasma perhexiline
      concentration was within the therapeutic range at 0.24 mg l-1 (IQR 0.12-0.44),
      the median atrial concentration was 6.02  mg kg-1 (IQR 2.70-9.06) and median
      ventricular concentration was 10.0 mg kg-1 (IQR 5.76-13.1). Atrial (r2 = 0.76)
      and ventricular (r2 = 0.73) perhexiline concentrations were closely and directly
      correlated with plasma concentrations (both P < 0.001). The median atrial :
      plasma ratio was 21.5 (IQR 18.1-27.1), ventricular : plasma ratio was 34.9 (IQR
      24.5-55.2) and ventricular : atrial ratio was 1.67 (IQR 1.39-2.22). Using
      multiple regression, the best model for predicting steady-state atrial
      concentration included plasma perhexiline, heart rate and age (r2 = 0.83).
      Ventricular concentrations were directly correlated with plasma perhexiline
      concentration and length of therapy (r2 = 0.84). CONCLUSIONS: This study
      demonstrates that plasma perhexiline concentrations are predictive of myocardial
      drug concentrations, a major determinant of drug effect. However, net myocardial
      perhexiline uptake is significantly modulated by patient age, potentially via
      alteration of myocardial:extracardiac drug uptake.

PMID- 24117488
TI  - Protective effect of a direct renin inhibitor in acute murine model of
      cardiotoxicity and nephrotoxicity.
AB  - This study aimed to investigate the possible protective effects of aliskiren
      against doxorubicin (DXR)-induced cardiorenal injury and to identify the
      mechanisms involved. Intraperitoneal administration of DXR (15 mg/kg, body
      weight, as a single dose) caused significant induction in the levels of
      angiotensin I, caspase-3, lactate dehydrogenase (LDH), lipid peroxidation
      malondialdehyde (MDA), urea, and creatinine. Concomitant decline in the levels of
      albumin and total protein in plasma, reduction in reduced glutathione (GSH), and
      antiperoxidative enzyme superoxide dismutase (SOD) levels followed by
      ultrastructural alterations in the myocardial and renal tissues were also
      observed. Oral administration of aliskiren (100 mg/kg, for a period of 14 days)
      significantly prevented all these DXR-induced adverse effects and maintained the
      rats near to normal status. However, telmisartan (10 mg/kg) pretreatment has
      shown slight protection in DXR-induced renal injury as evidenced by broadening of
      podocyte foot process and narrowing of slit pore diameter. The results of
      aliskiren were compared with telmisartan which was used as reference in this
      study. These results suggested that aliskiren has protective effects against
      acute model of DXR-induced cardiotoxicity and nephrotoxicity, implying that
      plasma renin activity plays a role in DXR-induced cardio-renal injury.

PMID- 24117489
TI  - Morphological and cytochemical studies of peripheral blood cells of Schizothorax
      prenanti.
AB  - The morphological and cytochemical studies of peripheral blood cells of
      Schizothorax prenanti were studied by light and electron microscopy.
      Erythrocytes, thrombocytes and three types of leucocytes, lymphocytes,
      neutrophils and monocytes, were distinguished and characterized. In addition to
      mature erythrocytes, immature and dividing erythrocytes were observed. A few
      organelles such as mitochondria were distributed in the cytoplasm of
      erythrocytes. Lymphocytes with heavily clumped heterochromatic nucleus and
      minimal cytoplasm were classified into small and large lymphocytes. Three
      different populations of granules, with distinctive ultrastructural aspect, were
      observed in neutrophils. Monocytes were the fewest leucocytes possessing rich
      organelles, phagocytized materials and vacuoles. Thrombocytes with various types
      were the most abundant blood cells among leucocytes and contained a prominent
      nucleus with dense bands of heterochromatin and many cytoplasmic vacuoles.
      Periodic acid-Schiff staining was positive in neutrophils, monocytes, lymphocytes
      and thrombocytes, but not in erythrocytes. Peroxidase-positive staining was
      observed in neutrophils and monocytes, but not in erythrocytes, lymphocytes and
      thrombocytes. Only neutrophils were positive for oil red O. Except for
      erythrocytes, the other blood cells stained positively for acid phosphatase. Only
      neutrophils and monocytes were positive for alpha-naphthyl acetate esterase. None
      of the cells studied were positive for alkaline phosphatase. The morphologic and
      cytochemical features of blood cells of S. prenanti are similar to those of other
      fish. This investigation may be helpful as a tool to monitor the health status of
      cultured S. prenanti and will grant early detection of clinical pathology. 

PMID- 24117490
TI  - Inflammation induces multinucleation of Microglia via PKC inhibition of
      cytokinesis, generating highly phagocytic multinucleated giant cells.
AB  - Microglia are brain macrophages, which can undergo multinucleation to give rise
      to multinucleated giant cells that accumulate with ageing and some brain
      pathologies. However, the origin, regulation and function of multinucleate
      microglia remain unclear. We found that inflammatory stimuli, including
      lipopolysaccharide, amyloid beta, alpha-synuclein, tumour necrosis factor-alpha
      and interferon gamma, but not interleukin-4, induced multinucleation of cultured
      microglia: primary rat cortical microglia and the murine microglial cell line BV
      2. Inflammation-induced multinucleation was prevented by a protein kinase C (PKC)
      inhibitor Go6976 (100 nM) and replicated by a PKC activator phorbol myristate
      acetate (160 nM). Multinucleation was reversible and not because of cell fusion
      or phagocytosis, but rather failure of cytokinesis. Time-lapse imaging revealed
      that some dividing cells failed to abscise, even after formation of long
      cytoplasmic bridges, followed by retraction of bridge and reversal of cleavage
      furrow to form multinucleate cells. Multinucleate microglia were larger and 2-4
      fold more likely to phagocytose large beads and both dead and live PC12 cells. We
      conclude that multinucleate microglia are reversibly generated by inflammation
      via PKC inhibition of cytokinesis, and may have specialized
      functions/dysfunctions including the phagocytosis of other cells. Inflammation
      resulted in the accumulation of multiple nuclei per cell in cultured microglia.
      This multinucleation was reversible and due to a PKC-dependent block of the last
      step of cell division. Multinucleate microglia were larger and had a greater
      capacity to phagocytose other cells, suggesting they might remove neurons in the
      brain.

PMID- 24117491
TI  - Allostatic load and health: Can perinatal epidemiology lead the way forward?

PMID- 24117492
TI  - Myo-inositol oxygenase is important for the removal of excess myo-inositol from
      syncytia induced by Heterodera schachtii in Arabidopsis roots.
AB  - The enzyme myo-inositol oxygenase is the key enzyme of a pathway leading from myo
      inositol to UDP-glucuronic acid. In Arabidopsis, myo-inositol oxygenase is
      encoded by four genes. All genes are strongly expressed in syncytia induced by
      the beet cyst nematode Heterodera schachtii in Arabidopsis roots. Here, we
      studied the effect of a quadruple myo-inositol oxygenase mutant on nematode
      development. We performed metabolite profiling of syncytia induced in roots of
      the myo-inositol oxygenase quadruple mutant. The role of galactinol in syncytia
      was studied using Arabidopsis lines with elevated galactinol levels and by
      supplying galactinol to wild-type seedlings. The quadruple myo-inositol oxygenase
      mutant showed a significant reduction in susceptibility to H. schachtii, and
      syncytia had elevated myo-inositol and galactinol levels and an elevated
      expression level of the antimicrobial thionin gene Thi2.1. This reduction in
      susceptibility could also be achieved by exogenous application of galactinol to
      wild-type seedlings. The primary function of myo-inositol oxygenase for syncytium
      development is probably not the production of UDP-glucuronic acid as a precursor
      for cell wall polysaccharides, but the reduction of myo-inositol levels and
      thereby a reduction in the galactinol level to avoid the induction of defence
      related genes. 

PMID- 24117493
TI  - Is therapeutic hypothermia the real cause of fluid retention and hyponatraemia in
      neonates with perinatal asphyxia? Authors' reply.

PMID- 24117494
TI  - Frost fatigue and spring recovery of xylem vessels in three diffuse-porous trees
      in situ.
AB  - Frost has been shown to cause frost fatigue (reduced cavitation resistance) in
      branch segments in the lab. Here, we studied the change in cavitation resistance
      and percent loss of conductivity (PLC) from fall to spring over 2 consecutive
      years in three diffuse-porous species in situ. We used the cavitron technique to
      measure P25 , P50 and P90 (the xylem pressure causing a 25, 50 and 90%
      conductivity loss) and PLC and stained functioning vessels. Cavitation resistance
      was reduced by 64-87% (in terms of P50 ), depending on the species and year. P25
      was impacted the most and P90 the least, changing the vulnerability curves from s
      to r-shaped over the winter in all three species. The branches suffered an
      almost complete loss of conductivity, but frost fatigue did not necessarily occur
      concurrently with increases in PLC. In two species, there was a trade-off between
      conduit size and vulnerability. Spring recovery occurred by growth of new
      vessels, and in two species by partial refilling of embolized conduits. Although
      newly grown and functioning conduits appeared more vulnerable to cavitation than
      year-old vessels, cavitation resistance generally improved in spring, suggesting
      other mechanisms for partial frost fatigue repair. 

PMID- 24117495
TI  - Analyses of beverage remains in drug rape cases revealing drug residues--the
      possibility of contamination from drug concentrated oral fluid or oral cavity
      contained tablets.
AB  - In drug-facilitated sexual assault (DFSA) cases, drug residues may be detected in
      beverage remains found in cups or glasses known to have been used by the victims.
      In this small naturalistic study, the possibility of beverages being
      contaminated, either by drug concentrated oral fluid or by oral cavity contained
      tablets, was investigated. Analysis of residues from cups containing soft drinks
      was performed by immunoassay and ultra-performance liquid chromatography-mass
      spectrometry (UPLC-MS/MS). Beverage with both added tablets and spiked oral fluid
      was investigated, as well as simulation of swallowing tablets. Only the residues
      from added tablets were positive with immunoassay, while drugs were detectable in
      all cups using more sensitive UPLC-MS/MS. In conclusion, the possibility of
      detecting drug residues in beverages due to a contamination, from either drug
      concentrated oral fluid or oral cavity contained tablets at a time of
      consumption, should be kept in mind when performing sensitive analysis. 

PMID- 24117496
TI  - Adding pulsatile vascular stimulation to venous systemic oxygen persufflation of
      liver grafts.
AB  - The effect of adding pulsatility to gaseous oxygen persufflation during liver
      preservation was studied in an isolated rat liver model. Livers from male Wistar
      rats were retrieved 30 min after cardiac arrest of the donor and subjected to 18
      h of cold storage. Some grafts were subjected to nonpulsatile or pulsatile
      gaseous oxygen persufflation. Graft viability was assessed thereafter upon warm
      reperfusion in vitro (n = 5 per group). Pulsatile persufflation significantly
      improved parenchymal integrity (enzyme release, bile flow) upon reperfusion, with
      respect to nonpulsatile persufflation or cold storage (CS) (e.g., max. release of
      alanine aminotransferase: 44 +/- 10 vs. 178 +/- 29 vs. 345 +/- 100 U/L; pulsatile
      vs. nonpulsatile persufflation vs. CS).The effect was associated with the
      prevention of the ischemic decline in gene and protein expression of the
      vasoprotective Kruppel-like factor 2, increased perfusate levels of the
      endogenous vasodilator nitric oxide, and reduced portal vascular resistance upon
      reperfusion, while nonpulsatile persufflation was less effective (e.g., vascular
      resistance: 1235 +/- 108 vs. 1607 +/- 155 vs. 2215 +/- 208 Pa s/mL; pulsatile vs.
      nonpulsatile persufflation vs. CS). In conclusion, pulsatile mechanostimulation
      of the hepatovasculature seems a genuine protective mechanism, affecting early
      graft recovery upon reperfusion. 

PMID- 24117497
TI  - Effect of synchronized or desynchronized music listening during osteopathic
      treatment: an EEG study.
AB  - While background music is often used during osteopathic treatment, it remains
      unclear whether it facilitates treatment, and, if it does, whether it is
      listening to music or jointly listening to a common stimulus that is most
      important. We created three experimental situations for a standard osteopathic
      procedure in which patients and practitioner listened either to silence, to the
      same music in synchrony, or (unknowingly) to different desynchronized montages of
      the same material. Music had no effect on heart rate and arterial pressure pre-
      and posttreatment compared to silence, but EEG measures revealed a clear effect
      of synchronized versus desynchronized listening: listening to desynchronized
      music was associated with larger amounts of mu-rhythm event-related
      desynchronization (ERD), indicating decreased sensorimotor fluency compared to
      what was gained in the synchronized music listening condition. This result
      suggests that, if any effect can be attributed to music for osteopathy, it is
      related to its capacity to modulate empathy between patient and therapist and,
      further, that music does not systematically create better conditions for empathy
      than silence. 

PMID- 24117498
TI  - Extraction sockets: erratic healing impeding factors.
AB  - AIM: The aim of this exploratory study was to analyse prevalence of extraction
      sockets showing erratic healing and evaluate factors potentially impeding
      healing. METHODS: Erratic healing was defined as extraction sites showing
      clinical observations of fibrous scar tissue occupying the extraction site rather
      than bone following 12 or more weeks of healing. Computerized tomography was used
      to evaluate characteristics and calculate Hounsfield unit scores for sites
      showing erratic healing. RESULTS: A total of 1226 dental records from Seoul
      National University Dental Hospital archives including patients subject to
      extractions prior to implant placement were evaluated. Seventy subjects (5.71%)
      and 97 sites (4.24%) exhibited erratic extraction socket healing. Maxillary
      incisor/canine sites showed the lowest (0.47%), whereas mandibular molar sites
      the highest (5.41%) occurrence. In the multivariable analysis, erratic healing
      was more likely to occur in subjects <60 years old (OR = 2.23, 95%CI = 1.26
      3.94), subjects with hypertension (OR = 2.37, 95%CI = 1.24-4.55), in molar sites
      (OR = 4.91, 95%CI = 1.41-17.07), and following single tooth extractions (OR =
      2.98, 95%CI = 1.36-6.53). Computerized tomography showed the highest incidence of
      bone loss for the buccal wall (49.3%). CONCLUSION: Erratic extraction socket
      healing appears a not uncommon sequel and local factors seem to be major
      contributors to its occurrence.

PMID- 24117499
TI  - Reduced expression of alphaGlcNAc in Barrett's oesophagus adjacent to Barrett's
      adenocarcinoma--a possible biomarker to predict the malignant potential of
      Barrett's oesophagus.
AB  - AIMS: Gastric gland mucin contains O-glycans exhibiting terminal alpha1,4-linked
      N-acetylglucosamine residues (alphaGlcNAc). Recently we demonstrated that mice
      deficient in alphaGlcNAc in gastric gland mucin develop gastric adenocarcinoma
      spontaneously, indicating that alphaGlcNAc is a tumour suppressor for gastric
      cancer. However, the role of alphaGlcNAc in Barrett's oesophagus (BO) remains
      unknown. In this study, we investigated whether reduced alphaGlcNAc expression in
      BO is associated with development of Barrett's adenocarcinoma (BAC). METHODS AND
      RESULTS: Thirty-five BO lesions adjacent to BAC were examined by
      immunohistochemistry for alphaGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions
      without BAC obtained from patients with oesophageal squamous cell carcinoma were
      also analysed. Expression of alphaGlcNAc relative to its scaffold MUC6 in BO
      adjacent to BAC was reduced significantly compared to control BO. Decreased
      alphaGlcNAc expression in BO adjacent to BAC was particularly significant in
      patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells
      to the superficial muscularis mucosae. There was also a significant inverse
      correlation between alphaGlcNAc and CDX2 expression in BO adjacent to BAC.
      CONCLUSIONS: Decreased expression of alphaGlcNAc compared with MUC6 in BO is a
      possible hallmark in predicting BAC development.

PMID- 24117500
TI  - Does it matter how I perceive my nation? National symbols, national
      identification and attitudes toward immigrants.
AB  - We examined how the ways of imagining one's own nation relate to the relationship
      between national identification and individuals' attitudes towards immigrants.
      National imagination is studied through two types of national symbols
      representing the nation in terms of confrontation between groups (i.e., war and
      sports) and a unique entity (i.e., nature and traditional culture). We found that
      national identification was positively associated with the degree to which
      individuals perceived their nation through a historical war and sports, which, in
      turn, enhanced negative attitudes toward immigrants. Unexpectedly, the degree to
      which individuals perceived their nation through nature and traditional culture
      was positively associated with positive intergroup attitudes. The results
      emphasize that the degree to which individuals perceive their nation through
      different national symbols is an important factor for understanding intergroup
      relations. 

PMID- 24117501
TI  - What is your diagnosis? Scapular mass in a Chinese hamster.

PMID- 24117502
TI  - Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype and stressful
      life events interact to predict preschool-onset depression: a replication and
      developmental extension.
AB  - BACKGROUND: Scientific enthusiasm about gene * environment interactions, spurred
      by the 5-HTTLPR (serotonin transporter-linked polymorphic region) * SLEs
      (stressful life events) interaction predicting depression, have recently been
      tempered by sober realizations of small effects and meta-analyses reaching
      opposing conclusions. These mixed findings highlight the need for further
      research. Converging evidence suggests that the effects of 5-HTTLPR genotype may
      be neurodevelopmental in origin, but we are not aware of empirical studies that
      have investigated whether the 5-HTTLPR genotype * SLE interaction predicts
      preschool-onset depression (PO-MDD), the earliest validated form of depression.
      METHODS: Children (n = 234) aged 3-5 were recruited for a longitudinal study
      designed to examine PO-MDD. In a comprehensive baseline assessment, the child's
      primary caregivers completed questionnaires and were interviewed about their
      child's behaviors, psychiatric symptoms, and exposure to SLEs. RESULTS: A 5
      HTTLPR * SLEs interaction emerged, such that children homozygous for the short
      allele were more susceptible to depression in the context of elevated SLE than
      long allele carriers. In contrast, at low SLE exposure, short allele homozygotes
      had fewer depressive symptoms. The data were best fit by a plasticity model with
      a substantial reduction in fit by diathesis-stress models. CONCLUSIONS: Extending
      studies in adult and adolescent populations, these data suggest that 5-HTTLPR
      genotype may provide plasticity to environmental influence, for better or worse.
      Specifically, children homozygous for the short allele were more susceptible to
      the depressogenic effects of SLEs but benefitted, in the form of reduced
      depressive symptoms, in the context of relatively benign environmental conditions
      (i.e. relatively low SLE exposure). These data highlight the importance of
      examining gene * environment interactions across development, environment, and
      outcome but should be interpreted cautiously given the small sample size.

PMID- 24117503
TI  - Optimising delivery of care in coeliac disease - comparison of the benefits of
      repeat biopsy and serological follow-up.
AB  - BACKGROUND: The majority of deleterious health consequences of coeliac disease
      (CD) are most likely to be secondary to intestinal inflammation; hence, mucosal
      recovery is a desirable goal of therapy. Follow-up in CD is controversial and
      serological response is often used as a surrogate for histological recovery.
      AIMS: To inform the clinical management of CD using comparative serological and
      histological data from a biopsy-driven pathway of care. METHODS: A retrospective
      analysis of the Cambridge Coeliac Clinic database of 595 patients routinely
      followed up by biopsy and serology. RESULTS: Paired biopsy results were available
      for 391 patients (15% seronegative). Persisting villous atrophy (VA) occurred in
      182 patients (47%). The sensitivity of anti-tissue transglutaminase (TTG)
      antibody for ongoing VA was only 43.6%. Information on dietetic management and
      further biopsy to assess response was available for 94 initially unresponsive
      patients, in whom targeted dietetic intervention by removal of identified gluten
      sources or avoidance of trace amounts of gluten led to resolution of persistent
      VA in 50%. The effects of institution of a formal care pathway are analysed in
      298 patients. Discharge to primary care and clinical management was facilitated
      by the information derived from repeat biopsy. CONCLUSIONS: Serology appears to
      be a poor surrogate marker for mucosal recovery on a gluten-free diet; dietary
      assessment fails to identify a potential gluten source in many patients with
      ongoing villous atrophy. The benefits of re-biopsy on diet include stratification
      of patients with coeliac disease suitable for early discharge from secondary care
      or those requiring more intensive clinical management.

PMID- 24117504
TI  - Dramatic shift in the infantile hemangioma treatment paradigm at a single
      institution.
AB  - Historically the first line of treatment for infantile hemangiomas (IHs) has been
      oral corticosteroids, but because of recent discoveries recognizing the
      effectiveness of oral and topical beta-blockers, IH management is dynamically
      changing. With these new treatment options, some physicians are altering the way
      they manage IHs despite having little evidence-based data on the treatment
      methods. Highlighting treatment changes at a single large tertiary pediatric
      referral center, we conclude that despite the numerous studies already published
      on this topic, more reliable prospective studies are needed to determine the
      safety, efficacy, and best treatment algorithms for the use of topical and oral
      beta-blockers for the treatment of IHs. 

PMID- 24117506
TI  - An innovative biologic recycling process of leukoreduction filters to produce
      active human antimicrobial peptides.
AB  - BACKGROUND: Human neutrophil peptides (HNPs) 1 to 3 are the major antimicrobial
      peptides of the azurophilic granules of neutrophils. They represent an important
      arm of the innate immune system. Their production by chemical synthesis and
      recombinant technologies is expensive and limited by technical constraints due to
      their composition and the presence of three disulfide bonds. STUDY DESIGN AND
      METHODS: We have developed an original approach based on the purification of the
      natural human defensins HNPs 1 to 3 from neutrophils trapped on leukoreduction
      filters used in blood processing. The purification of HNPs 1 to 3 from these
      filters is performed in two steps: extraction of HNPs 1 to 3 retained in the
      filters followed by their immunoprecipitation. Studies were performed to
      determine the stability of defensins in the filters stored at room temperature.
      The activity of HNPs 1 to 3 obtained by our rapid protocol was validated by
      determining minimal inhibitory concentrations (MICs) against six reference
      bacterial strains and 12 clinical isolates. RESULTS: The human defensins HNPs 1
      to 3 extracted from leukoreduction filters displayed high antimicrobial activity
      against tested strains, with MIC values between 0.12 and 1 MUg/mL. Kinetics
      assays showed the appearance of activity 15 minutes after peptide addition.
      Moreover, we found that the HNPs 1 to 3 purified from leukoreduction filters that
      had been stored for 45 days at room temperature remained active. CONCLUSION:
      Leukoreduction filters provide a rich and safe source of active human defensins
      HNPs 1 to 3. Moreover, the stability of the peptides in filters stored at room
      temperature allows envisaging a large-scale development of the process.

PMID- 24117505
TI  - Rab GTPases associate with isolated lipid droplets (LDs) and show altered content
      after ethanol administration: potential role in alcohol-impaired LD metabolism.
AB  - BACKGROUND: Alcoholic liver disease is manifested by the presence of fatty liver,
      primarily due to accumulation of hepatocellular lipid droplets (LDs). The
      presence of membrane-trafficking proteins (e.g., Rab GTPases) with LDs indicates
      that LDs may be involved in trafficking pathways known to be altered in ethanol
      (EtOH) damaged hepatocytes. As these Rab GTPases are crucial regulators of
      protein trafficking, we examined the effect EtOH administration has on hepatic
      Rab protein content and association with LDs. METHODS: Male Wistar rats were pair
      fed Lieber-DeCarli diets for 5 to 8 weeks. Whole liver and isolated LD fractions
      were analyzed. Identification of LDs and associated Rab proteins was performed in
      frozen liver or paraffin-embedded sections followed by immunohistochemical
      analysis. RESULTS: Lipid accumulation was characterized by larger LD vacuoles and
      increased total triglyceride content in EtOH-fed rats. Rabs 1, 2, 3d, 5, 7, and
      18 were analyzed in postnuclear supernatant (PNS) as well as LDs. All of the Rabs
      were found in the PNS, and Rabs 1, 2, 5, and 7 did not show alcohol-altered
      content, while Rab 3d content was reduced by over 80%, and Rab 18 also showed
      EtOH-induced reduction in content. Rab 3d was not found to associate with LDs,
      while all other Rabs were found in the LD fractions, and several showed an EtOH
      related decrease (Rabs 2, 5, 7, 18). Immunohistochemical analysis revealed the
      enhanced content of a LD-associated protein, perilipin 2 (PLIN2) that was
      paralleled with an associated decrease of Rab 18 in EtOH-fed rat sections.
      CONCLUSIONS: Chronic EtOH feeding was associated with increased PLIN2 and altered
      Rab GTPase content in enriched LD fractions. Although mechanisms driving these
      changes are not established, further studies on intracellular protein trafficking
      and LD biology after alcohol administration will likely contribute to our
      understanding of fatty liver disease.

PMID- 24117507
TI  - Implication of novel bis-imidazopyridines for management of Alzheimer's disease
      and establishment of its role on protein phosphatase 2A activity in brain.
AB  - OBJECTIVES: The objective of this study was to synthesize and identify potential
      leads for the management of Alzheimer's disease (AD). METHODS: A series of bis
      imidazopyridines were synthesized and assessed preclinically for anti
      inflammatory and antioxidant activity in aluminium chloride-induced rat model for
      AD. The two targets, anti-inflammatory and antioxidant, hold a significant
      relevance in AD. The compounds were also screened for their role of protein
      phosphatase 2A (PP2A) activity in brain which is responsible for tau
      dephosphorylation and alleviation of AD. KEY FINDINGS: The results of our study
      identified NIPERAMCD-KTB7 (dose: 50 mg/kg bodyweight, orally), as a potential
      molecule with good inhibitory activity in acute (67% oedema protection) as well
      as chronic (61% oedema protection) model of inflammation. This compound also
      showed good antioxidant activity as inferred from the inhibition of lipid
      peroxidation and superoxide dismutase activity in rats at the dose mentioned
      above. More significantly, PP2A activity was found to be increased in the brains
      of the animals treated with NIPERAMCD-KTB7 suggesting its potential role in
      management of AD. CONCLUSIONS: These preliminary findings indicate that NIPERAMCD
      KTB7 holds potential to serve as a basic lead for further structural modification
      and development of other new chemical entities for combating AD.

PMID- 24117508
TI  - Socioeconomic factors associated with pediatric diabetic ketoacidosis admissions
      in Southern West Virginia.
AB  - OBJECTIVE: Diabetic Ketoacidosis (DKA) is a well-known complication in children
      with type 1 diabetes mellitus (T1DM) with a mortality rate estimated at 2%. A
      previous study identified that T1DM children of non-Caucasian race with Medicaid
      insurance had increased incidence of DKA admissions. The aim of this study is to
      identify the socioeconomic factors associated with DKA admissions in West
      Virginia (WV). DESIGN AND METHODS: Retrospective chart review of patients
      admitted to the paediatric intensive care unit with DKA in Charleston, WV from
      January 2007-December 2010. Included subjects were 1-18 years of age and those
      with type 1 diabetes of >6 months duration. Admission rates were compared with
      the normal population distribution in WV. The data collection tool included
      multiple socioeconomic factors and HbA1c. RESULTS: We reviewed a total of 167
      patients with an admitting diagnosis of DKA; 57% were female, 43% male. Average
      age was 13.5 years +/- 2.7; 56.4% were covered by Medicaid/Chips (WV state
      insurance) and 43.6% by commercial payers. 11.9% were African American and 88.1%
      were Caucasian. The average HbA1c was 10.85 +/- 2.36%. Higher risks for DKA
      included those with HbA1c >14%, African American children (OR 17.4, CI 4-73) and
      children with Medicaid/Chips insurance (OR 9.3, 95% CI 1.1-76.2). CONCLUSIONS:
      This study identifies socioeconomic factors associated with children admitted for
      DKA in WV. Patients at higher risk for DKA include those with elevated HbA1c,
      African American race and those covered by Medicaid/CHIPS (thereby presumed lower
      socioeconomic status). Findings can be utilized to identify patients at highest
      risk for DKA and implementation of prevention strategies.

PMID- 24117509
TI  - Biopsy findings of symptomatic cerebral X-linked adrenoleucodystrophy and
      histological differentiation from multiple sclerosis.

PMID- 24117510
TI  - Justification for conscience exemptions in health care.
AB  - Some bioethicists argue that conscientious objectors in health care should have
      to justify themselves, just as objectors in the military do. They should have to
      provide reasons that explain why they should be exempt from offering the services
      that they find offensive. There are two versions of this view in the literature,
      each giving different standards of justification. We show these views are each
      either too permissive (i.e. would result in problematic exemptions based on
      conscience) or too restrictive (i.e. would produce problematic denials of
      exemption). We then develop a middle ground position that we believe better
      combines respect for the conscience of healthcare professionals with concern for
      the duties that they owe to patients. Our claim, in short, is that insofar as
      objectors should have to justify themselves, they should have to do it according
      to the standard that we defend rather than according to the standards that others
      have developed. 

PMID- 24117511
TI  - Development of chitosan conjugated DNA vaccine against nodavirus in Macrobrachium
      rosenbergii (De Man, 1879).
AB  - The protective efficacy of a DNA construct containing extra small virus antisense
      (XSVAS) gene of nodavirus encapsulated with chitosan nanoparticles (NPs) was
      investigated in giant freshwater prawn Macrobrachium rosenbergii (De Man, 1879).
      The delivery was carried out using oral and immersion methods. A plasmid
      concentration of 100 ng MUL(-1) when conjugated with chitosan NPs was found to be
      more effective in increasing the survivability of the infected prawn. The
      particle mean size, zeta potential and loading efficiency percentage were 297 nm,
      27 mV and 85%, respectively. The ability of the chitosan to form a complex with
      the plasmid was studied by agarose gel electrophoresis. The NPs were
      characterized by atomic force microscopy (AFM). Persistence study showed the
      presence of the DNA construct up to 30th day post-treatment. The oral treatment
      was found to be better than the immersion treatment for delivery of the chitosan
      conjugated DNA construct. This is probably the first report on the delivery of
      nanoconjugated DNA construct in M. rosenbergii, against nodavirus. 

PMID- 24117512
TI  - New blisters in a patient treated for Stevens-Johnson syndrome/toxic epidermal
      necrolysis.

PMID- 24117513
TI  - Determination of sIgE to rPhl p 1 is sufficient to diagnose grass pollen allergy.
AB  - BACKGROUND: New diagnostic tools such as the basophil activation test (BAT) and
      component-resolved diagnosis (CRD) are promising for Hymenoptera venom or food
      allergy. A clear benefit for inhalant allergens has not yet been shown. Our aim
      was to compare new and established tests for grass pollen allergy. METHODS: Forty
      nine patients with grass pollen allergy and 47 controls were prospectively
      enrolled in the study. A symptom score was calculated for each patient.
      Conjunctival provocation tests (CPT), skin prick tests (SPT), BAT, and sIgE
      determination including CRD were performed. Sensitivity and specificity were
      compared and results were correlated with the symptom score. RESULTS: Single
      determination of sIgE to rPhl p 1 showed the best balance between sensitivity
      (98%) and specificity (92%). Use of additional components, such as rPhl p 2 and
      5, did not increase sensitivity. Generally, sensitivity of tests was high: SPT
      100%, ISAC-112 100%, sIgE to timothy grass 98%, BAT 98%, ISAC-103 84%, and CPT
      83%. Specificity ranged from 79% (SPT) to 96% (CPT). All test results and
      calculated values (e.g. ratio sIgE/tIgE) did not correlate with symptom severity.
      Asymptomatic sensitization to timothy grass in controls was rare in the CAP (11%)
      and predominantly due to Phl p 1 sensitization. CONCLUSION: rPhl p 1 was
      sufficient to diagnose grass pollen allergy, and sIgE patterns were the same in
      symptomatically and asymptomatically sensitized subjects. The testing of multiple
      components was of minor importance, and no test correlated with symptom severity.

PMID- 24117514
TI  - Smartphone-Based Android app for Determining UVA Aerosol Optical Depth and Direct
      Solar Irradiances.
AB  - This research describes the development and evaluation of the accuracy and
      precision of an Android app specifically designed, written and installed on a
      smartphone for detecting and quantifying incident solar UVA radiation and
      subsequently, aerosol optical depth at 340 and 380 nm. Earlier studies
      demonstrated that a smartphone image sensor can detect UVA radiation and the
      responsivity can be calibrated to measured direct solar irradiance. This current
      research provides the data collection, calibration, processing, calculations and
      display all on a smartphone. A very strong coefficient of determination of 0.98
      was achieved when the digital response was recalibrated and compared to the
      Microtops sun photometer direct UVA irradiance observations. The mean percentage
      discrepancy for derived direct solar irradiance was only 4% and 6% for
      observations at 380 and 340 nm, respectively, lessening with decreasing solar
      zenith angle. An 8% mean percent difference discrepancy was observed when
      comparing aerosol optical depth, also decreasing as solar zenith angle decreases.
      The results indicate that a specifically designed Android app linking and using a
      smartphone image sensor, calendar and clock, with additional external narrow
      bandpass and neutral density filters can be used as a field sensor to evaluate
      both direct solar UVA irradiance and low aerosol optical depths for areas with
      low aerosol loads.

PMID- 24117515
TI  - The U.K. service level audit of insulin pump therapy in adults.
AB  - AIMS: The National Institute for Health and Clinical Excellence (NICE) published
      guidelines for the use of continuous subcutaneous insulin infusion in 2008
      (technology appraisal 151). The first U.K.-wide insulin pump audit took place in
      2012 with the aim of determining adherence to the guidance issued in NICE
      technology appraisal 151. The results of the adult service level audit are
      reported here. METHODS: All centres providing continuous subcutaneous insulin
      infusion services to adults with diabetes in the U.K. were invited to
      participate. Audit metrics were aligned to technology appraisal 151. Data entry
      took place online using a DiabetesE formatted data collection tool. RESULTS: One
      hundred and eighty-three centres were identified as delivering adult continuous
      subcutaneous insulin infusion services in the U.K., of which 178 (97.3%)
      participated in the audit. At the time of the audit, 13 428 adults were using
      insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three
      per cent of centres did not report any barriers in obtaining funding for patients
      who fulfilled NICE criteria. The mean number of consultant programmed activities
      dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0
      8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3)
      and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which
      39, 61 and 60%, respectively, were not formally funded. CONCLUSIONS: The
      prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well
      below the expectation of NICE (15-20%) and that of other European countries (>
      15%) and the U.S.A. (40%). This may be attributable, in part, to lack of
      healthcare professional time needed for identification and training of new pump
      therapy users.

PMID- 24117516
TI  - Erythromycin-induced genotoxicity and hepatotoxicity in mice pups treated during
      prenatal and postnatal period.
AB  - The main aim of this study was to investigate the oxidative stress, genotoxicity
      and cytotoxicity of erythromycin (EMC) in pups of treated dams in gestation as
      well as the lactation period (LP). The two doses of EMC were compared using
      intraperitoneal (i.p.) route in two different periods, that is, in gestation
      period and in the LP. The rationale behind selection of i.p. route is because of
      the fact that EMC gets degrades in acidic pH of the stomach. The doses of EMC
      used were clinically equivalent dose (CED; EMC 14.2 mg/kg, i.p.) and a lower dose
      (EMC 10 mg/kg, i.p.) than CED. EMC toxicities in mice pups were evaluated using
      various parameters such as micronucleus (MN) test in peripheral blood and bone
      marrow, malondialdehyde (MDA) assay, glutathione (GSH reduced) assay and
      histopathological assessment in liver tissue. The CED of EMC led to a significant
      increase in MDA and decreased in GSH concentration in pups' liver tissue in both
      gestation and LPs and also to a significant increase in MN frequency in both
      peripheral blood and bone marrow cells of pups. There were no significant
      toxicities at a lower dose than CED. There were also some chronic findings with
      liver histopathological examination at CED. It is thus concluded that EMC
      accentuates the oxidative stress, cytotoxicity and DNA damage in pups of their
      postnatal life; hence, EMC should be avoided in the pregnancy and also in the LP.

PMID- 24117517
TI  - Systematic review of efficacy and outcomes of salvage liver transplantation after
      primary hepatic resection for hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Upfront liver transplantation is the gold standard in the
      treatment of patients with hepatocellular carcinoma (HCC) and cirrhosis, but a
      shortage of donor organs negatively impacts on survival outcomes, with
      significant disease progression during long waiting lists. This systematic review
      evaluates the safety and efficacy of salvage liver transplantation (SLT) as
      treatment for recurrent HCC after initial hepatic resection. METHODS: Electronic
      searches of Pubmed, Embase, and Medline databases identified 130 abstracts, from
      which 16 eligible studies comprising 319 patients were selected for review.
      Studies adopting SLT following primary hepatic resection for recurrent HCC with
      more than five patients were included. Demographic details, morbidity and
      mortality indices, and survival outcomes were collected from each study and were
      tabulated. RESULTS: All patients included in the studies had liver cirrhosis,
      with the majority being Child-Pugh A (50%) and B (33%). The etiology of liver
      disease was hepatitis B in the majority of patients (84%). Disease recurrence
      occurred in 27-80% of patients at a median of 21.4 months (range 14.5-34)
      following initial resection. SLTs were performed on 41% of recurrences, and were
      associated with biliary complications (8%), infection (11%), bleeding (8%), and
      vascular complications (7%). There were 18 perioperative deaths (5.6%). The
      median 1-, 3-, and 5-year overall and disease-free survival was 89%, 80%, and
      62%, and 86%, 68%, and 67%, respectively. CONCLUSION: Synthesis of available
      observational studies suggests that SLT following primary hepatic resection is a
      highly applicable strategy with long-term survival outcomes that are comparable
      to upfront liver transplantation.

PMID- 24117518
TI  - Biological nitrogen fixation and biomass accumulation within poplar clones as a
      result of inoculations with diazotrophic endophyte consortia.
AB  - Sustainable production of biomass for bioenergy relies on low-input crop
      production. Inoculation of bioenergy crops with plant growth-promoting endophytes
      has the potential to reduce fertilizer inputs through the enhancement of
      biological nitrogen fixation (BNF). Endophytes isolated from native poplar
      growing in nutrient-poor conditions were selected for a series of glasshouse and
      field trials designed to test the overall hypothesis that naturally occurring
      diazotrophic endophytes impart growth promotion of the host plants. Endophyte
      inoculations contributed to increased biomass over uninoculated control plants.
      This growth promotion was more pronounced with multi-strain consortia than with
      single-strain inocula. Biological nitrogen fixation was estimated through (15)N
      isotope dilution to be 65% nitrogen derived from air (Ndfa). Phenotypic
      plasticity in biomass allocation and branch production observed as a result of
      endophyte inoculations may be useful in bioenergy crop breeding and engineering
      programs.

PMID- 24117519
TI  - Lack of sleep could increase obesity in children and too much television could be
      partly to blame.
AB  - AIM: To examine the bidirectional relationship between short sleep duration and
      body mass index (BMI). A secondary aim was to investigate whether reduced
      physical activity and increased screen time (television and computer use)
      mediated these associations. METHODS: This study utilised data from the
      Longitudinal Study of Australian Children, which is an observational cohort study
      of Australian children. The sample included 2984 (52.4% boys) children followed
      from 4 to 5 years of age until 8 to 9 years of age. Sleep duration, screen time
      and covariates were reported by parents, with BMI measured objectively. Cross
      lagged modelling investigated the bidirectional association between sleep
      duration and BMI; lagged panel mediation modelling examined physical activity and
      screen time as potential mediators. RESULTS: Short sleep duration at 4 to 5 years
      of age was significantly associated with higher BMI at 8 to 9 years of age (beta=
      -.07, p = .044). The relationship between short sleep duration at 4 to 5 years of
      age and higher BMI at 8 to 9 years of age was partially mediated by increased
      television viewing at 6 to 7 years of age (beta = -.01, 95% confidence interval [
      .02, -.002]). CONCLUSION: Short sleep duration could be a risk factor for obesity
      in children. Increased television viewing may be one mechanism underlying this
      longitudinal relationship.

PMID- 24117520
TI  - Corticosterone targets distinct steps of synaptic transmission via concentration
      specific activation of mineralocorticoid and glucocorticoid receptors.
AB  - Hippocampal neurons are affected by chronic stress and have a high density of
      cytoplasmic mineralocorticoid and glucocorticoid receptors (MR and GR). Detailed
      studies on the genomic effects of the stress hormone corticosterone at
      physiologically relevant concentrations on different steps in synaptic
      transmission are limited. In this study, we tried to delineate how activation of
      MR and GR by different concentrations of corticosterone affects synaptic
      transmission at various levels. The effect of 3-h corticosterone (25, 50, and 100
      nM) treatment on depolarization-mediated calcium influx, vesicular release and
      properties of miniature excitatory post-synaptic currents (mEPSCs) were studied
      in cultured hippocampal neurons. Activation of MR with 25 nM corticosterone
      treatment resulted in enhanced depolarization-mediated calcium influx via a
      transcription-dependent process and increased frequency of mEPSCs with larger
      amplitude. On the other hand, activation of GR upon 100 nM corticosterone
      treatment resulted in increase in the rate of vesicular release via the genomic
      actions of GR. Furthermore, GR activation led to significant increase in the
      frequency of mEPSCs with larger amplitude and faster decay. Our studies indicate
      that differential activation of the dual receptor system of MR and GR by
      corticosterone targets the steps in synaptic transmission differently.

PMID- 24117521
TI  - HeartWare ventricular assist device as bridge to transplant in children and
      adolescents.
AB  - Limited options do exist for mechanical circulatory support as a bridge to
      transplantation in the pediatric population. This is especially true when it
      comes to intracorporeal technologies. We describe our successful experience with
      the use of HeartWare ventricular assist devices (HeartWare, Inc., Framingham, MA,
      USA) in three patients <16 years of age, as a successful and feasible bridge to
      transplant in patients weighing greater than 20 kg. 

PMID- 24117522
TI  - Auditory startle reflex inhibited by preceding self-action.
AB  - A startle reflex to a startle pulse is inhibited when preceded by a prestimulus.
      We introduced a key-press action (self-action) or an 85 dB noise burst as a
      prestimulus, followed by a 115 dB noise burst as a startle pulse. We manipulated
      temporal offsets between the prestimulus and the startle pulse from 30-1,500 ms
      to examine whether self-action modulates the startle reflex and the temporal
      properties of the modulatory effect. We assessed eyeblink reflexes by
      electromyography. Both prestimuli decreased reflexes compared to pulse-alone
      trials. Moreover, the temporal windows of inhibition were different between the
      types of prestimuli. A faster maximal inhibition and narrower temporal window in
      self-action trials suggest that preceding self-action inhibits the startle reflex
      and allows prediction of the coming pulse in different ways from auditory
      prestimuli. 

PMID- 24117523
TI  - Practical compassions: repertoires of practice and compassion talk in acute
      mental healthcare.
AB  - This article reports an exploratory study of the concept of compassion in the
      work of 20 mental health practitioners in a UK Midlands facility. Using notions
      of practice derived from phenomenology and Bourdieusian sociology and notions of
      emotional labour we identify two contrasting interpretive repertoires in
      discussions of compassion. The first, the practical compassion repertoire, evokes
      the practical, physical and bodily aspects of compassion. It involves organising
      being with patients, playing games, anticipating disruption and taking them
      outside for cigarettes. Practitioners described being aware that these practical,
      bodily activities could lead to patients 'opening up', disclosing their interior
      concerns and enabling practical, compassionate mental health work to take place.
      In contrast, the second, organisational repertoire, concerns organisational
      constraints on compassionate practice. The shortage of staff, the record-keeping
      and internal processes of quality control were seen as time-greedy and apt to
      detract from contact with patients. The findings are discussed in relation to
      Bourdieu and Merleau-Ponty's phenomenological accounts of practice and habit and
      set in context in the growing interest in placing compassion centrally in
      healthcare. We also explore how the exercise of compassion in the way our
      participants describe it can afford the more effective exercise of medical power.

PMID- 24117524
TI  - Observational etiologic research: part 3-case-control studies: it's all about the
      source population.

PMID- 24117526
TI  - Targeted therapies for sarcomas: new roles for the pathologist.
AB  - Sarcomas are a heterogeneous family of mesenchymal malignancies that employ an
      impressive variety of pathogenetic mechanisms. The traditional role of the
      pathologist in this field has been to ensure accurate diagnosis and histological
      grading to direct therapy. More recently, with the advent of targeted therapies
      directed at particular molecular alterations, the role of the pathologist has
      expanded and increased awareness of the genetic features of sarcomas is needed to
      deliver optimal multidisciplinary care. This review discusses these trends and
      briefly enumerates many of the molecular derangements and targeted agents
      currently used or under investigation in soft tissue sarcoma. A few sarcomas are
      highlighted in more detail to illustrate how pathologists can exert positive
      influence on patient care - not just through diagnosis and grading, but also with
      molecular characterizations. Featured sarcomas include alveolar soft part
      sarcoma, dermatofibrosarcoma protuberans, gastrointestinal stromal tumour,
      inflammatory myofibroblastic tumour and PEComas. 

PMID- 24117527
TI  - Combustion and toxic gas production from disposable barbecues in enclosures.
AB  - The production of carbon monoxide from disposable barbecues in an enclosed room
      has been investigated. Hazard calculations have shown that lethal concentrations
      of CO and CO2 can be produced easily. Burning rates and the relative formation of
      CO and CO2 depend on the ambient oxygen concentration. Smoke does not correlate
      with CO concentration as it is mostly produced by the combustion of volatile
      hydrocarbons added to facilitate ignition. In a typical room, this results in
      smoke clearing before the maximum CO concentration is reached. Smoke obscuration
      is therefore a poor indicator of the danger posed by CO. This is an important
      observation for those discovering or attempting to resuscitate or rescue comatose
      victims. Dilution caused by ventilation is described numerically and has allowed
      total volumes of CO and CO2 produced to be estimated. 

PMID- 24117525
TI  - Focal thalamic degeneration from ethanol and thiamine deficiency is associated
      with neuroimmune gene induction, microglial activation, and lack of
      monocarboxylic acid transporters.
AB  - BACKGROUND: Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in
      alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with
      lesions to the thalamus (THAL). Although TD alone can cause WE, the high
      incidence in alcoholism suggests that TD and ethanol (EtOH) interact. METHODS:
      Mice in control, TD, or EtOH groups alone or combined were studied after 5 or 10
      days of treatment. THAL and entorhinal cortex (ENT) histochemistry and mRNA were
      assessed. RESULTS: Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed
      activated microglia, proinflammatory gene induction and THAL neurodegeneration
      that was greater than that found with TD alone (TD5), whereas 10 days resulted in
      marked THAL degeneration and microglial-neuroimmune activation in both groups. In
      contrast, 10 days of TD did not cause ENT degeneration. Interestingly, in ENT,
      TD10 activated microglia and astrocytes more than EtOH-TD10. In THAL, multiple
      astrocytic markers were lost consistent with glial cell loss. TD blocks glucose
      metabolism more than acetate. Acetate derived from hepatic EtOH metabolism is
      transported by monocarboxylic acid transporters (MCT) into both neurons and
      astrocytes that use acetyl-CoA synthetase (AcCoAS) to generate cellular energy
      from acetate. MCT and AcCoAS expression in THAL is lower than ENT prompting the
      hypothesis that focal THAL degeneration is related to insufficient MCT and AcCoAS
      in THAL. To test this hypothesis, we administered glycerin triacetate (GTA) to
      increase blood acetate and found it protected the THAL from TD-induced
      degeneration. CONCLUSIONS: Our findings suggest that EtOH potentiates TD-induced
      THAL degeneration through neuroimmune gene induction. The findings support the
      hypothesis that TD deficiency inhibits global glucose metabolism and that a
      reduced ability to process acetate for cellular energy results in THAL focal
      degeneration in alcoholics contributing to the high incidence of Wernicke
      Korsakoff syndrome in alcoholism.

PMID- 24117528
TI  - Sinus augmentation using BMP-2 in a bovine hydroxyapatite/collagen carrier in
      dogs.
AB  - AIM: The objective of this study was to determine the efficacy of bone
      morphogenetic protein 2 (BMP-2) in a bovine hydroxyapatite/collagen (BHC) carrier
      to augment bone formation in a canine nasal sinus model. METHODS: Eight mongrel
      dogs, approximately 12 months old and 30 kg in weight were used. Following
      preparation of bilateral sinus access windows, BHC alone (control) or loaded with
      E. coli-derived BMP-2 at 0.1 mg/ml was implanted in four animals, and BHC loaded
      with E. coli-derived BMP-2 at 0.5 and 1.5 mg/ml was implanted in four animals.
      The animals were euthanized at 20 weeks when block sections were obtained for
      micro-computed tomography and histometric analyses. RESULTS: Total augmented
      volumes did not differ significantly between groups. Histometric analysis showed
      significantly enhanced bone formation for the BMP-2 groups compared with control.
      CONCLUSION: BMP-2 in a BHC carrier, even at the low 0.1-mg/ml concentration,
      induces osteogenic activity, enhancing local bone formation in a canine sinus
      model.

PMID- 24117529
TI  - Am I my profession's keeper?
AB  - Conscientious refusal is distinguished by its peculiar attitude towards the
      obligations that the objector refuses: the objector accepts the authority of the
      institution in general, but claims a right of conscience to refuse some
      particular directive. An adequate ethics of conscientious objection will, then,
      require an account of the institutional obligations that the objector claims a
      right to refuse. Yet such an account must avoid two extremes: 'anarchism,' where
      obligations apply only insofar as they match individual conscience; and
      'totalitarianism,' where even immoral obligations bind us. The challenge is to
      explain institutional obligations in such a way that an agent can be obligated to
      act against conscience, yet can object if the institution's orders go too far.
      Standard accounts of institutional obligations rely on individual autonomy,
      expressed through consent. This paper rejects the Consent model; a better
      understanding of institutional obligations emerges from reflecting on the
      intersecting goods produced by institutions and the intersecting autonomy of
      numerous distinct agents rather than only one. The paper defends
      'Professionalism' as a grounding of professional obligations. The professional
      context can justify acting against conscience but more often that context partly
      shapes the professional conscience. Yet Professionalism avoids totalitarianism by
      distinguishing between (mere) injustice and abuse. When institutions are - or we
      conscientiously believe them to be - merely unjust, their directives still
      obligate us; when they are abusive, however, they do not. Finally, the paper
      applies these results to the problem of conscientious refusal in general and
      specifically to controversial reproduction cases. 

PMID- 24117530
TI  - Epidemiological modelling of attention-deficit/hyperactivity disorder and conduct
      disorder for the Global Burden of Disease Study 2010.
AB  - BACKGROUND: The most recent Global Burden of Disease Study (GBD 2010) is the
      first to include attention-deficit/hyperactivity disorder (ADHD) and conduct
      disorder (CD) for burden quantification. We present the epidemiological profiles
      of ADHD and CD across three time periods for 21 world regions. METHODS: A
      systematic review of global epidemiology was conducted for each disorder (based
      on a literature search of the Medline, PsycInfo and EMBASE databases). A Bayesian
      metaregression tool was used to derive prevalence estimates by age and sex in
      three time periods (1990, 2005 and 2010) for 21 world regions including those
      with little or no data. Prior expert knowledge and covariates were applied to
      each model to adjust suboptimal data. Final prevalence output for ADHD were
      adjusted to reflect an equivalent value if studies had measured point prevalence
      using multiple informants while final prevalence output for CD were adjusted to
      reflect a value equivalent to CD only. RESULTS: Prevalence was pooled for males
      and females aged 5-19 years with no difference found in global prevalence between
      the three time periods. Male prevalence of ADHD in 2010 was 2.2% (2.0-2.3) while
      female prevalence was 0.7% (0.6-0.7). Male prevalence of CD in 2010 was 3.6% (3.3
      4.0) while female prevalence was 1.5% (1.4-1.7). ADHD and CD were estimated to be
      present worldwide with ADHD prevalence showing some regional variation while CD
      prevalence remained relatively consistent worldwide. CONCLUSIONS: We present the
      first prevalence estimates of both ADHD and CD globally and for all world
      regions. Data were sparse with large parts of the world having no estimates of
      either disorder. Epidemiological studies are urgently needed in certain parts of
      the world. Our findings directly informed burden quantification for GBD 2010. As
      mental disorders gained increased recognition after the first GBD study in 1990,
      the inclusion of ADHD and CD in GBD 2010 ensures their importance will be
      recognized alongside other childhood disorders.

PMID- 24117531
TI  - Effect of meal and antisecretory agents on the pharmacokinetics of
      danoprevir/ritonavir in healthy volunteers.
AB  - OBJECTIVES: To evaluate the effect of a low- and high-fat meal and co
      administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir
      boosted danoprevir (DNVr). METHODS: In this randomised, open-label, cross-over
      study, healthy subjects received a single dose of DNVr. In group 1, DNVr was
      administered while fasting or with a low-fat or high-fat meal. In group 2, DNVr
      was administered alone or with ranitidine 150 mg (single dose) or omeprazole 40
      mg (multiple doses). KEY FINDINGS: Group 1 (n = 16): relative to fasting
      conditions, food slightly prolonged absorption but did not alter the extent of
      absorption. DNV area under the plasma concentration-time curve extrapolated to
      infinity (AUC0-infinity), maximum plasma concentration (C(max)), and plasma
      concentration 12 h after administration (C12h) geometric mean ratios (GMR%) (90%
      confidence interval (CI)) with a low-fat meal were 92.3 (80.2-106), 61.8 (51.0
      74.9) and 95.2 (80.9-112), versus fasting conditions, and with a high-fat meal
      99.5 (86.4-115), 58.9 (48.5-71.6) and 101 (86.0-119). Group 2 (n = 13):
      ranitidine or omeprazole had no clinically significant effect on DNV
      pharmacokinetics. DNV AUC0-infinity, Cmax and C12h GMR% (90% CI) with ranitidine:
      81.9 (68.3-98.1), 104 (86.9-123) and 87.5 (69.3-111), and with omeprazole: 83.0
      (67.4-102), 92.7 (70.6-122) and 93.3 (65.6-133). CONCLUSIONS: The absence of
      clinically relevant effects of food, ranitidine or omeprazole on DNVr
      pharmacokinetics suggests that DNVr can be administered without regard to meals
      and in combination with H2 antagonists or proton pump inhibitors.

PMID- 24117532
TI  - Early lexical development and risk of verbal and nonverbal cognitive delay at
      school age.
AB  - AIM: To characterise the relationship between preschool lexical delay and
      language comprehension and nonverbal intelligence at school age. METHODS: The
      mothers of 2724 children completed the MacArthur Communicative Development
      Inventory when their child reached 1.5 years and the Language Development Survey
      and the Parent Report of Children's Ability at 2.5 years. When the children were
      6 years old, we assessed vocabulary comprehension and nonverbal intelligence
      using Dutch batteries for language and nonverbal intelligence. RESULTS:
      Demographic factors explained 9.9% of the variance in vocabulary comprehension
      and 8.7% of the variance in nonverbal intelligence at 6 years. Male gender, low
      maternal education and non-Western ethnic background predicted vocabulary
      comprehension delay at 6 years. Lexical development at 1.5 and 2.5 years
      explained only 3.8% of the variance in language comprehension at the age of six.
      Late onset expressive vocabulary delay increased the risk of language
      comprehension and nonverbal intelligence delay at 6 years (OR=2.31, 95% CI: 1.62
      3.29 and OR=1.74, 95% CI: 1.17-2.58, respectively). CONCLUSION: Sociodemographic
      factors are important predictors of delays in language and nonverbal abilities as
      children enter school. In contrast, early expressive lexical delays, in
      particular before the age of two, have limited predictive power for language
      delays at the age of six.

PMID- 24117533
TI  - Improved blood utilization using real-time clinical decision support.
AB  - BACKGROUND: We analyzed blood utilization at Stanford Hospital and Clinics after
      implementing real-time clinical decision support (CDS) and best practice alerts
      (BPAs) into physician order entry (POE) for blood transfusions. STUDY DESIGN AND
      METHODS: A clinical effectiveness (CE) team developed consensus with a suggested
      transfusion threshold of a hemoglobin (Hb) level of 7 g/dL, or 8 g/dL for
      patients with acute coronary syndromes. The CDS was implemented in July 2010 and
      consisted of an interruptive BPA at POE, a link to relevant literature, and an
      "acknowledgment reason" for the blood order. RESULTS: The percentage of blood
      ordered for patients whose most recent Hb level exceeded 8 g/dL ranged at
      baseline from 57% to 66%; from the education intervention by the CE team August
      2009 to July 2010, the percentage decreased to a range of 52% to 56% (p = 0.01);
      and after implementation of CDS and BPA, by end of December 2010 the percentage
      of patients transfused outside the guidelines decreased to 35% (p = 0.02) and has
      subsequently remained below 30%. For the most recent interval, only 27% (767 of
      2890) of transfusions occurred in patients outside guidelines. Comparing 2009 to
      2012, despite an increase in annual case mix index from 1.952 to 2.026, total red
      blood cell (RBC) transfusions decreased by 7186 units, or 24%. The estimated net
      savings for RBC units (at $225/unit) in purchase costs for 2012 compared to 2009
      was $1,616,750. CONCLUSION: Real-time CDS has significantly improved blood
      utilization. This system of concurrent review can be used by health care
      institutions, quality departments, and transfusion services to reduce blood
      transfusions.

PMID- 24117534
TI  - Neuropathological features of Japanese familial amyotrophic lateral sclerosis
      with p.N352S mutation in TARDBP.

PMID- 24117535
TI  - Tissue distribution of hepatopancreatic parvo-like virus of shrimp in freshwater
      rice-field crab, Paratelphusa hydrodomous (Herbst).
AB  - An attempt was made to determine the replication efficiency of hepatopancreatic
      parvo-like virus (HPV) of shrimp in different organs of freshwater rice-field
      crab Paratelphusa hydrodomous (Herbst) using bioassay, PCR, RT-PCR, ELISA,
      Western blot and q-PCR analyses. Another attempt was made to use this crab as an
      alternative to penaeid shrimp for the large-scale production of HPV. This crab
      was found to be highly susceptible to HPV by intramuscular injection. The
      systemic HPV infection was confirmed by PCR and Western blot analyses in
      freshwater crab. The expression of capsid protein gene in different organs of
      infected crab was revealed by RT-PCR analysis. Indirect ELISA was used to
      quantify the capsid protein in different organs of the crab. The copy number of
      HPV in different organs of the infected crab was quantified by q-PCR. The results
      revealed a steady decrease in CT values in different organs of the infected crab
      during the course of infection. The viral inoculum that was prepared from
      different organs of the infected crab caused significant mortality in post-larvae
      of tiger prawn, Penaeus monodon (Fabricius). The results revealed that this rice
      field crab could be used as an alternative host for HPV replication and also for
      large-scale production of HPV. 

PMID- 24117536
TI  - Model for end-stage liver disease score versus Maddrey discriminant function
      score in assessing short-term outcome in alcoholic hepatitis.
AB  - BACKGROUND AND AIMS: The Maddrey Discriminant Function (mDF) score and the Model
      for End-Stage Liver Disease (MELD) score are standard prognostic scores for
      predicting disease severity and mortality in alcoholic hepatitis (AH).This
      prospective study compared the MELD score and the mDF score as predictors of
      short-term outcome in AH. METHODS: The admission MELD score and the mDF score
      were assessed in 47 patients with a diagnosis of AH in the Himalayan Institute
      Hospital, Dehradun, India and the concordance (C) statistics of the two scores
      for 28-day mortality were determined and compared. RESULTS: Both the MELD score
      and the mDF score on day 1 were significantly higher in non-survivors than in
      survivors (P = 0.0001 each). The C-statistic for 28-day mortality for the MELD
      score was 0.91 (P < 0.0001, 95% confidence interval [CI] 0.79-0.97) and for the
      mDF score 0.90 (P < 0.0001, 95% CI 0.78-0.97). There was no significant
      difference between the C-statistics of the two scores (P = 0.83, 95% CI -0.07 to
      0.09). For predicting 28-day mortality, the optimal MELD score of > 19
      (sensitivity 91.6% and specificity 85.7%) corresponded to the mDF score of > 52.8
      (sensitivity 91.6% and specificity 82.8%). CONCLUSIONS: Both the MELD score and
      the mDF score at admission were strong and equally good predictors of 28-day
      mortality in patients with AH, but the optimal mDF score corresponding to optimal
      MELD score was higher than the conventional one. Thus, MELD score may be used as
      an alternative to mDF score for predicting short-term mortality in AH with an
      advantage.

PMID- 24117537
TI  - T cell suppression in vitro during Toxoplasma gondii infection is the result of
      IL-2 competition between Tregs and T cells leading to death of proliferating T
      cells.
AB  - A reduced proliferation to T cell mitogens is observed in vitro in murine cells
      isolated during the acute phase of Toxoplasma gondii infection. Foxp3(+)
      regulatory T cells (Tregs) mediate this suppression, which is interleukin (IL)-2
      dependent. In this work, we analysed the mechanism of this Treg-mediated
      suppression. We found that removal of antigen-presenting cells (APC) from spleen
      cells from infected mice did not modify suppression but further elimination of
      Tregs led to a restored proliferation, demonstrating that Tregs mediate
      suppression in the absence of APC. Production of IL-2 by T cells from infected
      animals was abolished but partially restored when Tregs were removed. However, IL
      2 levels and T cell proliferation were restored when Tregs and T cells were
      separated by transwells, indicating that Tregs require close proximity with T
      cells to induce suppression. Tregs from infected mice were able to reduce
      proliferation of CTLL-2 cells in the classical IL-2 bioassay, strongly suggesting
      that Tregs compete with T cells for IL-2. We found that T cells from infected
      mice died after a few rounds of division in vitro, but addition of recombinant IL
      2 or removal of Tregs abolished this effect. Our results showed that suppression
      of T cell proliferation during acute Toxoplasma gondii infection is the result of
      death of proliferating T cells by Treg-mediated IL-2 competition. Thus,
      immunosuppression is due to death of proliferating T cells as a consequence of
      low IL-2 availability. 

PMID- 24117538
TI  - A 67-year-old woman with resolving atrophic patches.

PMID- 24117539
TI  - Identification of potential platelet alloantigens in the Equidae family by
      comparison of gene sequences encoding major platelet membrane glycoproteins.
AB  - BACKGROUND: Platelet alloantigens in horses may play an important role in the
      development of neonatal alloimmune thrombocytopenia (NAIT). OBJECTIVE: The
      objective of this study was to evaluate genes encoding major platelet
      glycoproteins within the Equidae family in an effort to identify potential
      alloantigens. METHODS: DNA was isolated from blood samples obtained from Equidae
      family members, including a Holsteiner-Oldenburg cross, a Quarter horse, a
      donkey, and a Plains zebra (Equus burchelli). Gene sequences encoding equine
      platelet membrane glycoproteins IIb, IIIa (integrin subunits alphaIIb and beta3),
      Ia (integrin subunit alpha2), and Ibalpha were determined using PCR. Gene
      sequences were compared to the equine genome available on GenBank. Polymorphisms
      that would be predicted to result in amino acid changes on platelet surfaces were
      documented and compared with known alloantigenic sites documented on human
      platelets. RESULTS: Amino acid differences were predicted based on nucleotide
      sequences for all 4 genes. Nine differences were documented for alphaIIb, 5
      differences were documented for beta3, 7 differences were documented for alpha2,
      and 16 differences were documented for Ibalpha outside the macroglycopeptide
      region. CONCLUSIONS: This study represents the first effort at identifying
      potential platelet alloantigens in members of the Equidae Family based on
      evaluation of gene sequences. The data obtained form the groundwork for
      identifying potential platelet alloantigens involved in transfusion reactions and
      neonatal alloimmune thrombocytopenia (NAIT). More work is required to determine
      whether the predicted amino acid differences documented in this study play a role
      in alloimmunity, and whether other polymorphisms not detected in this study are
      present that may result in alloimmunity.

PMID- 24117540
TI  - Long noncoding RNAs responsive to Fusarium oxysporum infection in Arabidopsis
      thaliana.
AB  - Short noncoding RNAs have been demonstrated to play important roles in regulation
      of gene expression and stress responses, but the repertoire and functions of long
      noncoding RNAs (lncRNAs) remain largely unexplored, particularly in plants. To
      explore the role of lncRNAs in disease resistance, we used a strand-specific RNA
      sequencing approach to identify lncRNAs responsive to Fusarium oxysporum
      infection in Arabidopsis thaliana. Antisense transcription was found in c. 20% of
      the annotated A. thaliana genes. Several noncoding natural antisense transcripts
      responsive to F. oxysporum infection were found in genes implicated in disease
      defense. While the majority of the novel transcriptionally active regions (TARs)
      were adjacent to annotated genes and could be an extension of the annotated
      transcripts, 159 novel intergenic TARs, including 20 F. oxysporum-responsive
      lncTARs, were identified. Ten F. oxysporum-induced lncTARs were functionally
      characterized using T-DNA insertion or RNA-interference knockdown lines, and five
      were demonstrated to be related to disease development. Promoter analysis
      suggests that some of the F. oxysporum-induced lncTARs are direct targets of
      transcription factor(s) responsive to pathogen attack. Our results demonstrated
      that strand-specific RNA sequencing is a powerful tool for uncovering hidden
      levels of transcriptome and that IncRNAs are important components of the
      antifungal networks in A. thaliana.

PMID- 24117541
TI  - Welcome to the wild, wild north: conscientious objection policies governing
      Canada's medical, nursing, pharmacy, and dental professions.
AB  - In Canada, as in many developed countries, healthcare conscientious objection is
      growing in visibility, if not in incidence. Yet the country's health professional
      policies on conscientious objection are in disarray. The article reports the
      results of a comprehensive review of policies relevant to conscientious objection
      for four Canadian health professions: medicine, nursing, pharmacy and dentistry.
      Where relevant policies exist in many Canadian provinces, there is much
      controversy and potential for confusion, due to policy inconsistencies and
      terminological vagueness. Meanwhile, in Canada's three most northerly territories
      with significant Aboriginal populations, whose already precarious health is
      influenced by funding and practitioner shortages, there are major policy gaps
      applicable to conscientious objection. In many parts of the country, as a result
      of health professionals' conscientious refusals, access to some legal health
      services - including but not limited to reproductive health services such as
      abortion - has been seriously impeded. Although policy reform on conscientious
      conflicts may be difficult, and may generate strenuous opposition from some
      professional groups, for the sake of both patients and providers, such policy
      change must become an urgent priority. 

PMID- 24117542
TI  - Effective use of alteplase for occluded tunneled venous catheter in hemodialysis
      patients.
AB  - Despite their propensity for significant infectious and mechanical complications,
      tunneled central venous catheters (CVCs) have become a common means of vascular
      access in the world for patients requiring chronic hemodialysis for end-stage
      renal disease. The objective of this study was to explore if cryopreserved
      solutions of the thrombolytic agent alteplase could be used as an effective,
      safe, and economically reasonable alternative in hemodialysis patients with
      occluded tunneled CVC. Patients requiring chronic hemodialysis and presenting
      with occluded tunneled CVC received a sufficient volume of the alteplase solution
      to fill the occluded catheter. To make alteplase economically feasible, it was
      diluted to 1-mg/mL aliquots and they were stored at -20 degrees C until use.
      Eighty-one patients accounting for 179 attempted clearances were assessable for
      efficacy. One hundred forty-seven (82.1%) of the 179 catheter clearance attempts
      resulted in successful catheter clearance after one dose. Twenty-seven (15.1%) of
      all occluded CVCs were successful after two doses whereas five (2.8%) were not.
      No adverse events were reported. Cryopreserved 1-mg/mL aliquots of alteplase are
      safe and effective in the clearance of occluded CVC for hemodialysis patients. 

PMID- 24117543
TI  - Possible involvement of cathepsin B/D and caspase-3 in deferoxamine-related
      neuroprotection of early brain injury after subarachnoid haemorrhage in rats.
AB  - AIMS: Deferoxamine (DFX) has recently been shown to have a neuroprotective effect
      in animal models of subarachnoid haemorrhage (SAH). However, the precise
      mechanisms underlying these effects remain unclear. Our previous studies found
      that iron overload in lysosomes leads to lysosomal membrane damage and rupture,
      and then induces cell apoptosis in the oxidative stress conditions in vitro. We
      therefore analysed the time-course of the two of major lysosomal cathepsins
      (cathepsin B/D) and caspase-3 expression in brain and evaluated how DFX might
      affect these proteins and the parameters concerning early brain injury (EBI)
      after SAH. METHODS: We investigated the time-course of cathepsin B/D and caspase
      3 expression in the cortex after SAH in rats. Furthermore, we assessed the effect
      of DFX on regulation of cathepsin B/D and caspase-3 and EBI following SAH. All
      SAH animals were subjected to a single injection of autologous blood into the
      prechiasmatic cistern. Protein concentrations were measured using Western blot
      analysis and immunohistochemistry. The extent of brain oedema was measured using
      the wet/dry method. Blood-brain barrier (BBB) permeability was assessed using IgG
      extravasation. Cortical apoptosis was examined using terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labelling (TUNEL). RESULTS: Cathepsin B/D and
      caspase-3 were up-regulated in the cortices of affected rats after SAH. Levels of
      both peaked at 48-h post-SAH. After intraperitoneal DFX administration, the
      elevated expression of cathepsin B/D and caspase-3 was down-regulated in the
      cortex 48 h after blood injection. In the DFX-treated group, early brain damage
      events, such as brain oedema, BBB impairment, cortical apoptosis, and alterations
      in clinical behaviour were significantly ameliorated relative to vehicle-treated
      SAH rats. CONCLUSIONS: These results suggest that the lysosomal membrane may be
      damaged after SAH, which leads to the release of proteases (cathepsin B/D) and
      activates the apoptotic pathway. Iron overload may be one key mechanism
      underlying SAH-induced oxidative stress and DFX may protect the lysosomal
      membrane, inhibit the release of cathepsin B/D, and ameliorate EBI by suppressing
      iron overload in the acute phase of SAH.

PMID- 24117544
TI  - Airway dysfunction in elite athletes--an occupational lung disease?
AB  - Airway dysfunction is prevalent in elite endurance athletes and when left
      untreated may impact upon both health and performance. There is now concern that
      the intensity of hyperpnoea necessitated by exercise at an elite level may be
      detrimental for an athlete's respiratory health. This article addresses the
      evidence of causality in this context with the aim of specifically addressing
      whether airway dysfunction in elite athletes should be classified as an
      occupational lung disease. The approach used highlights a number of concerns and
      facilitates recommendations to ensure airway health is maintained and optimized
      in this population. We conclude that elite athletes should receive the same
      considerations for their airway health as others with potential and relevant
      occupational exposures. 

PMID- 24117545
TI  - Bullous dermolysis of the newborn: four new cases and clinical review.
AB  - Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis
      bullosa caused by mutations in type VII collagen resulting in disorganized
      anchoring fibrils and sublamina densa blister formation. Disease activity is
      usually confined to the first year of life, with restoration of physiologic type
      VII collagen localization. We report four new cases of BDN and review the utility
      of immunofluorescence mapping in establishing the diagnosis. 

PMID- 24117547
TI  - Medical students, mindsets and learning behaviour change.

PMID- 24117548
TI  - Understanding medical student goal orientation: the role of self-theories.

PMID- 24117549
TI  - Learning in the health professions: what does self-regulation have to do with it?

PMID- 24117550
TI  - Feedback: it's all in the CHAT.

PMID- 24117551
TI  - When I say...emotion in medical education.

PMID- 24117552
TI  - Believing is seeing: how people's beliefs influence goals, emotions and
      behaviour.
AB  - INTRODUCTION: Health care professionals work and learn in complex environments.
      Some are able to continue learning from their practice and the challenges it
      presents, whereas others refrain from investing more effort when faced with
      setbacks. This paper discusses a social cognitive model of motivation that helps
      to explain the different kinds of behaviour that emerge when individuals are
      confronted with challenges. SELF-THEORIES: Self-theories (people's theories on
      what competence is and means for the self) play a major role in establishing the
      goals people set for themselves, the emotions they experience and the meanings
      they attach to situations. These self-views are often not explicitly articulated
      and are therefore called 'implicit' ('self-') theories. Social cognitive research
      suggests there are two distinct ways of thinking about one's personal attributes:
      entity theorists view a trait as a fixed, concrete internal entity, whereas
      incremental theorists instead believe a trait to be something malleable that can
      be developed or cultivated through effort. Holding an entity theory leads one to
      set performance goals and to harbour concerns about performing well and making a
      good impression. Holding an incremental theory tends to lead one to set learning
      goals, and to focus less on performance and more on spending time and effort in
      determining which strategies work. DISCUSSION: The current literature on self
      theories is used to explore the relevance of these theories in medical education
      in three contexts: (i) it is argued that, in order to support lifelong learning,
      both individual and organisational efforts fit best with an incremental outlook
      on professional development; (ii) if it is to move forward in the domain of
      feedback-seeking behaviour, medical education might benefit from a better
      understanding of the interactions among self-theories, feedback behaviour, and
      the pervading role of organisational culture, and (iii) the impact of self
      theories on assessors' evaluations of performance.

PMID- 24117553
TI  - Effects of longitudinal small-group learning on delivery and receipt of
      communication skills feedback.
AB  - OBJECTIVES: Although feedback is a critical component of learning, recent data
      suggest that learners may discount feedback they receive. The emotional threat
      inherent in feedback can contribute to its ineffectiveness, particularly for
      sensitive topics like communication skills. Longitudinal relationships among
      peers may increase their sense of safety and soften the perceived threat of
      feedback to allow students to give, receive and potentially more effectively
      incorporate feedback. We studied the effects of prior shared learning experiences
      among medical students in the delivery and receipt of feedback on clinical
      (communication) skills. METHODS: During a formative clinical skills examination,
      we divided Year 3 students at a US medical school into two subgroups comprising,
      respectively, small-group classmates from a 2-year longitudinal pre-clerkship
      clinical skills course (with prior peer-learning relationships), and peers with
      no prior shared small-group coursework. Students in both subgroups observed peers
      in a simulated clinical case and then provided feedback, which was videotaped,
      transcribed and coded. Feedback recipients also completed a survey on their
      perceptions of the feedback. RESULTS: Students valued the feedback they received
      and intended to enact it, regardless of whether they had prior peer-learning
      relationships. Coding of feedback revealed high specificity. Feedback providers
      who had prior peer-learning relationships with recipients provided more specific
      corrective feedback on communication skills than those with no such relationships
      (p = 0.014); there was no significant difference between subgroups in the
      provision of reinforcing feedback on communication skills. CONCLUSIONS: Year 3
      medical student peers can deliver specific feedback on clinical skills; prior
      peer-learning relationships in pre-clerkship clinical skills courses enrich the
      provision of specific corrective feedback about communication skills. Feedback
      between peers with pre-existing peer-learning relationships represents an
      additional and potentially underutilised method of helping students improve
      clinical skills in sensitive realms such as interpersonal communication.

PMID- 24117554
TI  - Do assessor comments on a multi-source feedback instrument provide learner
      centred feedback?
AB  - OBJECTIVES: Free-text comments in multi-source feedback are intended to
      facilitate change in the assessee's practice. This study was designed to utilise
      a large dataset of free-text comments obtained in a national pilot study in order
      to investigate how helpful these free-text comments may be to assessees. METHODS:
      We investigated: (i) which areas of performance are usually addressed by free
      text comments; (ii) to what extent assessors' (doctors, nurses, allied health
      professionals and clerical or managerial staff) comments correspond to assessees'
      (career-grade doctors) self-assessments, and (iii) whether the comments contain
      specific behavioural evidence and suggestions for change. Initially comments were
      read through to identify commonly recurring themes. A strong theme was
      'respondent-centredness', which refers to the extent to which comments focus on
      issues that are of value to the assessor rather than to the assessee's personal
      development. In response to this, the data were re-evaluated against predefined
      research questions to assess how constructive comments were for the assessee's
      personal development. RESULTS: Of 11,483 assessor forms, 4777 (42%) included free
      text comments. A total of 513 forms contained at least one below average score
      and 286 (56%) of these forms contained the assessor's free-text feedback. Free
      text comments were mostly rater-centred and addressed the effect of the assessee
      on the colleague's working life rather than areas of relevance to the assessee's
      personal development. A total of 1806 assessor/assessee pairs of comments were
      compared; most demonstrated clear differences of opinion or interpretation.
      Reliability and supportiveness were over-represented; clinical performance and
      personal development were under-represented. The comments were unlikely to
      provide specific behavioural evidence or to address how change might be
      initiated. CONCLUSIONS: Our data indicate that, in their current form, the
      overwhelming majority of free-text comments add little to facilitate improvement
      in assessees' personal development and performance.

PMID- 24117555
TI  - Explaining how faculty members act upon residents' feedback to improve their
      teaching performance.
AB  - CONTEXT: Responsiveness to feedback is a complex phenomenon that requires and
      receives attention. However, knowledge on the responsiveness of faculty members
      to residents' feedback on their teaching performance is lacking. Excellent
      teaching performance is essential to ensure patient safety and residents'
      learning in residency training. This study aims to increase our understanding of
      how faculty staff react to and act upon residents' feedback on their teaching
      performance. OBJECTIVES: This multi-specialty, multi-institution interview study
      was conducted to gain insight into: (i) how teaching faculty proceed after they
      have received residents' feedback on their teaching performance, and (ii) the
      factors that influence their progression. METHODS: Between August and December
      2011, 24 faculty members who had received formative feedback on their teaching
      performance through valid and reliable feedback systems participated in this
      study. They reflected upon their (re)action(s) during individual semi-structured
      interviews. The interview protocol and analysis were guided by a comprehensive
      transtheoretical framework describing and explaining stages and processes of
      behavioural change. RESULTS: Faculty staff involved in residency training used
      residents' feedback to different extents to adapt or improve their teaching
      performance. Important tipping points in the processes of change necessary for
      faculty staff to put feedback into practice were: experiencing negative emotions
      in themselves or recognising those in residents as a result of failure to act
      upon feedback; realising that something should be done with or without support
      from others, and making a strong commitment to change. In addition, having the
      confidence to act upon feedback and recognising the benefits of change were found
      to stimulate faculty members to change their teaching behaviour. CONCLUSIONS: The
      responsiveness of faculty members to residents' feedback on their teaching
      performance varies. The adapted transtheoretical framework explains how and why
      faculty members do or do not proceed to action after receiving residents'
      feedback. Given this, organising residents' feedback for faculty staff in a
      systematic way is a first step and is necessary to effect potential improvements
      in teaching performance.

PMID- 24117556
TI  - Faculty staff-guided versus self-guided ultrasound training for internal medicine
      residents.
AB  - OBJECTIVES: Ultrasonography is of growing importance within internal medicine
      (IM), but the optimal method of training doctors to use it is uncertain. In this
      study, the authors provide the first objective comparison of two approaches to
      training IM residents in ultrasonography. METHODS: In this randomised trial, a
      simulation-based ultrasound training curriculum was implemented during IM intern
      orientation at a tertiary care teaching hospital. All 72 incoming interns
      attended a lecture and were given access to online modules. Interns were then
      randomly assigned to a 4-hour faculty-guided (FG) or self-guided (SG) ultrasound
      training session in a simulation laboratory with both human and manikin models.
      Interns were asked to self-assess their competence in ultrasonography and
      underwent an objective structured clinical examination (OSCE) to assess their
      competence in basic and procedurally oriented ultrasound tasks. The primary
      outcome was the score on the OSCE. RESULTS: Faculty-guided training was superior
      to self-guided training based on the OSCE scores. Subjects in the FG training
      group achieved significantly higher OSCE scores on the two subsets of task
      completion (0.9-point difference, 95% confidence interval [CI] 0.27-1.54; p =
      0.008) and ultrasound image quality (2.43-point difference, 95% CI 1.5-3.36; p <
      0.001). Both training groups demonstrated an increase in self-assessed competence
      after their respective training sessions and there was little difference between
      the groups. Subjects rated the FG training group much more favourably than the SG
      training group. CONCLUSIONS: Both FG and SG ultrasound training curricula can
      improve the self-reported competence of IM interns in ultrasonography. However,
      FG training was superior to SG training in both skills acquisition and intern
      preference. Incorporating mandatory ultrasound training into IM residencies can
      address the perceived need for ultrasound training, improve confidence and
      procedural skills, and may enhance patient safety. However, the optimal training
      method may require significant faculty input.

PMID- 24117557
TI  - Students' self-explanations while solving unfamiliar cases: the role of
      biomedical knowledge.
AB  - OBJECTIVE: General guidelines for teaching clinical reasoning have received much
      attention, despite a paucity of instructional approaches with demonstrated
      effectiveness. As suggested in a recent experimental study, self-explanation
      while solving clinical cases may be an effective strategy to foster reasoning in
      clinical clerks dealing with less familiar cases. However, the mechanisms that
      mediate this benefit have not been specifically investigated. The aim of this
      study was to explore the types of knowledge used by students when solving
      familiar and less familiar clinical cases with self-explanation. METHODS: In a
      previous study, 36 third-year medical students diagnosed familiar and less
      familiar clinical cases either by engaging in self-explanation or not. Based on
      an analysis of previously collected data, the present study compared the content
      of self-explanation protocols generated by seven randomly selected students while
      solving four familiar and four less familiar cases. In total, 56 verbal protocols
      (28 familiar and 28 less familiar) were segmented and coded using the following
      categories: paraphrases, biomedical inferences, clinical inferences, monitoring
      statements and errors. RESULTS: Students provided more self-explanation segments
      from less familiar cases (M = 275.29) than from familiar cases (M = 248.71, p =
      0.046). They provided significantly more paraphrases (p = 0.001) and made more
      errors (p = 0.008). A significant interaction was found between familiarity and
      the type of inferences (biomedical versus clinical, p = 0.016). When self
      explaining less familiar cases, students provided significantly more biomedical
      inferences than familiar cases. CONCLUSIONS: Lack of familiarity with a case
      seems to stimulate medical students to engage in more extensive thinking during
      self-explanation. Less familiar cases seem to activate students' biomedical
      knowledge, which in turn helps them to create new links between biomedical and
      clinical knowledge, and eventually construct a more coherent mental
      representation of diseases. This may clarify the previously found positive effect
      that self-explanation has on the diagnosis of unfamiliar cases.

PMID- 24117558
TI  - A peer-reviewed collection of short reports from around the world on innovative
      approaches to medical education.

PMID- 24117559
TI  - Audiovisual use in anatomy laboratory facilitates learning.

PMID- 24117560
TI  - Medical school success strategies: proactive intervention examination.

PMID- 24117561
TI  - Drawings as snapshots of student cellular anatomy understanding.

PMID- 24117562
TI  - Curriculum for community-based nurses on care of older adults.

PMID- 24117563
TI  - Diabetes management: student nurses contribute using point-of-care testing.

PMID- 24117564
TI  - Evaluating logbooks to improve clerkship learning experiences.

PMID- 24117565
TI  - Infectious diseases evidence assessments: evidence-based medicine in practice.

PMID- 24117566
TI  - An hour on call: simulation for medical students.

PMID- 24117567
TI  - Medical students as managers of their university hospital.

PMID- 24117568
TI  - Training may impact shift work mentality in students.

PMID- 24117569
TI  - Enlivening journal clubs using a modified 'jigsaw' method.

PMID- 24117570
TI  - Journal club blog for faculty paediatricians.

PMID- 24117571
TI  - Fully engaged learning through 2.5-minute presentations.

PMID- 24117572
TI  - Patient perceptions of bedside teaching rounds.

PMID- 24117573
TI  - Tweeting during conferences: educational or just another distraction?

PMID- 24117574
TI  - Dialogue vodcasts: a qualitative assessment.

PMID- 24117575
TI  - Video or paper for delivery of problem-based learning cases?

PMID- 24117576
TI  - OSCE standards-setting procedure facilitated by digital technology.

PMID- 24117577
TI  - Technology and teaching: suicide risk assessment.

PMID- 24117578
TI  - Improving cancer teaching through videoconferenced multidisciplinary team
      meetings.

PMID- 24117579
TI  - Learning together in paediatric outreach clinics.

PMID- 24117580
TI  - Rewarding collaborative learning skills in the pre-clerkship curriculum.

PMID- 24117581
TI  - Developing a team orientation through team-level reflection and feedback.

PMID- 24117582
TI  - Professionalism and social media: an interprofessional learning activity.

PMID- 24117583
TI  - Integrating the caregiver perspective: an interprofessional opportunity.

PMID- 24117584
TI  - An interprofessional home visit curriculum for high-risk patients.

PMID- 24117585
TI  - Assessing residents' interprofessional conflict negotiation skills.

PMID- 24117586
TI  - 'Revelations of Cancer' course enhances students' interdisciplinary
      collaboration.

PMID- 24117587
TI  - Bioethical principles, clinical research and popular movies.

PMID- 24117588
TI  - Developing clinical communication skills: targeting the postgraduate years.

PMID- 24117589
TI  - DVD empathy simulations: an interventional study.

PMID- 24117590
TI  - Developing cultural competence in health care professionals: a fresh approach.

PMID- 24117591
TI  - Enhancing students' communication in an ethnic language.

PMID- 24117592
TI  - Nominal group technique: a tool for course evaluation.

PMID- 24117593
TI  - Enabling fresh perspectives on assessment via the performing arts.

PMID- 24117595
TI  - Pre-clerkship perceptions of women in surgery.

PMID- 24117596
TI  - A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel
      disease intolerant to azathioprine: an observational study, systematic review and
      meta-analysis.
AB  - BACKGROUND: Thiopurines maintain remission and modify disease course in
      inflammatory bowel disease. Use is limited by intolerance and subsequent drug
      withdrawal in approximately 17% of patients treated with azathioprine. Previous
      case series have addressed the success rates of re-treatment with mercaptopurine
      in these individuals. AIMS: To determine the rate of tolerance when trialling
      mercaptopurine in azathioprine-intolerant patients and the factors predictive of
      success, and to perform a systematic review and meta-analysis of these data with
      other published data sets. METHODS: A retrospective observational study of 149
      patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis)
      previously intolerant of azathioprine subsequently treated with mercaptopurine
      was performed. A meta-analysis was undertaken of all published studies of
      mercaptopurine use in azathioprine-intolerant patients (455 patients in 11
      included studies). RESULTS: Mercaptopurine was tolerated by 58% of azathioprine
      intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated
      mercaptopurine. A higher proportion of those in the meta-analysis with GI
      toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than
      those with flu-like illness (36%). Among those patients who ceased mercaptopurine
      for further adverse effects, 59% experienced the same adverse effect as they had
      with azathioprine. CONCLUSIONS: This meta-analysis shows that switching to
      mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine
      intolerant patients and may help optimise immunomodulatory therapy in
      inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD
      patients (except those with acute pancreatitis or bone marrow aplasia) before
      considering thiopurine intolerance.

PMID- 24117597
TI  - Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2
      diabetes insufficiently controlled on metformin (GetGoal-F1).
AB  - AIMS: To assess the efficacy and safety of one- and two-step dose-increase
      regimens of lixisenatide once daily in participants with Type 2 diabetes mellitus
      insufficiently controlled with metformin. METHODS: This was a randomized, double
      blind, placebo-controlled, parallel-group, multi-centre study enrolling
      participants with Type 2 diabetes (n = 484) treated with metformin. Participants
      were randomized to receive either lixisenatide in a one-step dose increase or a
      two-step dose increase vs. placebo for 24 weeks, followed by a >= 52-week
      variable double blind period. Primary outcome was HbA1c reduction at week 24.
      RESULTS: Lixisenatide one-/two-step once daily significantly improved HbA1c at
      week 24 compared with placebo (P < 0.0001) and allowed more participants to
      achieve HbA1c < 53 mmol/mol (< 7.0%) (P <= 0.0005). Improvements were observed in
      fasting plasma glucose (-0.5/-0.6 vs. +0.1 mmol/l; P < 0.001) and body weight (
      2.6/-2.7 vs. -1.6 kg; P < 0.005). At week 24, adverse events were reported by
      67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo,
      respectively--nausea and vomiting being reported most frequently. Symptomatic
      hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide
      and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be
      efficacious and well tolerated during the variable double-blind extension period
      of at least 52 weeks. CONCLUSIONS: Lixisenatide one- or two-step dose-increase
      regimens significantly improved glycaemic control and decreased body weight over
      24 weeks and during a long-term extension period without increasing
      hypoglycaemia. The study confirmed that tolerability in the one-step group was at
      least similar to the two-step dose increase, with nausea/vomiting and
      hypoglycaemia frequency being lower in the one-step regimen.

PMID- 24117598
TI  - Peripheral blood stem cell collection in low-weight children: retrospective
      comparison of two apheresis devices.
AB  - BACKGROUND: Apheresis is a major challenge in peripheral stem cell collection
      from low-weight children with cancer. Comparisons between the new apheresis
      device Optia (TerumoBCT) and the earlier COBE Spectra (CaridianBCT) have been
      performed in adults but not in low-weight children. The objective was to compare
      the performance of these two devices in small children. STUDY DESIGN AND METHODS:
      In this retrospective study, all patients were reviewed weighing less than 15 kg
      undergoing stem cell collection using the Optia device between April 2011 and
      April 2012. They were paired on weight in a 3:1 ratio with patients whose cells
      had been collected with the COBE Spectra since 2006. RESULTS: Six patients were
      treated with the Optia and were matched with 18 patients treated with the
      Spectra. No side effects occurred. Collection efficiency (CE) was similar between
      the two groups (50% vs. 47%), but CD34 cell blood clearance was lower with the
      Optia (0.4 mL/min/kg vs. 0.6 mL/min/kg, p < 0.01). Platelet (PLT) loss and
      hemoglobin (Hb) loss were significantly reduced with the Optia (respectively, 32%
      vs. 54%, p < 0.01; and 1.4 g/dL vs. 2.9 g/dL, p < 0.01). Apheresis duration was
      increased with the Optia (159 min vs. 134 min, p < 0.05). The cell product
      harvested with the Optia had a lower volume and lower hematocrit, but similar
      white blood cell and PLT content. CONCLUSION: Compared with the Spectra, the
      Optia allows similar CE with a reduced PLT and Hb loss but with a longer
      duration.

PMID- 24117599
TI  - In vivo quantification of neuro-glial metabolism and glial glutamate
      concentration using 1H-[13C] MRS at 14.1T.
AB  - Astrocytes have recently become a major center of interest in neurochemistry with
      the discoveries on their major role in brain energy metabolism. An interesting
      way to probe this glial contribution is given by in vivo (13) C NMR spectroscopy
      coupled with the infusion labeled glial-specific substrate, such as acetate. In
      this study, we infused alpha-chloralose anesthetized rats with [2-(13) C]acetate
      and followed the dynamics of the fractional enrichment (FE) in the positions C4
      and C3 of glutamate and glutamine with high sensitivity, using (1) H-[(13) C]
      magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two-compartment
      mathematical model to the measured time courses yielded a glial tricarboxylic
      acid (TCA) cycle rate (Vg ) of 0.27 +/- 0.02 MUmol/g/min and a glutamatergic
      neurotransmission rate (VNT ) of 0.15 +/- 0.01 MUmol/g/min. Glial oxidative ATP
      metabolism thus accounts for 38% of total oxidative metabolism measured by NMR.
      Pyruvate carboxylase (VPC ) was 0.09 +/- 0.01 MUmol/g/min, corresponding to 37%
      of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial
      fluxes (Vx (g) and Vx (n) ) were of the same order of magnitude as the respective
      TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 +/
      0.1 MUmol/g. The effect of spectral data quality on the fluxes estimates was
      analyzed by Monte Carlo simulations. In this (13) C-acetate labeling study, we
      propose a refined two-compartment analysis of brain energy metabolism based on
      (13) C turnover curves of acetate, glutamate and glutamine measured with state of
      the art in vivo dynamic MRS at high magnetic field in rats, enabling a deeper
      understanding of the specific role of glial cells in brain oxidative metabolism.
      In addition, the robustness of the metabolic fluxes determination relative to MRS
      data quality was carefully studied.

PMID- 24117600
TI  - Volume determination of fresh and dried bloodstains by means of optical coherence
      tomography.
AB  - The volume of bloodstains found on crime scenes may help forensic investigators
      reconstruct the location and kinematics of bloodletting events, as stain size,
      volume, and impact velocity are related. Optical coherence tomography was used as
      a method to determine the volume and volume ratio of dried and fresh bloodstains
      on both glass and irregular surfaces or deposited with an impact velocity. The
      volume of blood drops deposited on smooth glass surfaces was measured within a
      deviation of 2%. This deviation increased for droplets on irregular surfaces or
      deposited with an impact velocity. The volume ratio of dried and fresh
      bloodstains was equal to 19-28% depending on the individual donor and on the use
      of an anticoagulant. Optical coherence tomography is a good method to determine
      the volume of fresh and dried bloodstains in laboratory conditions and allows
      accurate determination of the dry/fresh ratio. 

PMID- 24117601
TI  - Aerobic and anaerobic oxidation of hydrogen by acidophilic bacteria.
AB  - While many prokaryotic species are known to use hydrogen as an electron donor to
      support their growth, this trait has only previously been reported for two
      acidophilic bacteria, Hydrogenobaculum acidophilum (in the presence of reduced
      sulfur) and Acidithiobacillus (At.) ferrooxidans. To test the hypothesis that
      hydrogen may be utilized more widely by acidophilic bacteria, 38 strains of
      acidophilic bacteria, including representatives of 20 designated and four
      proposed species, were screened for their abilities to grow via the dissimilatory
      oxidation of hydrogen. Growth was demonstrated in several species of acidophiles
      that also use other inorganic electron donors (ferrous iron and sulfur) but in
      none of the obligately heterotrophic species tested. Strains of At. ferrooxidans,
      At. ferridurans and At. caldus, grew chemolithotrophically on hydrogen, though
      those of At. thiooxidans and At. ferrivorans did not. Growth was also observed
      with Sulfobacillus acidophilus, Sb. benefaciens and Sb. thermosulfidooxidans,
      though not with other iron-oxidizing Firmicutes. Similarly, Acidimicrobium
      ferrooxidans grew on hydrogen, closely related acidophilic actinobacteria did
      not. Growth yields of At. ferrooxidans and At. ferridurans grown aerobically on
      hydrogen (c. 10(10)  cells mL(-1) ) were far greater than typically obtained
      using other electron donors. Several species also grew anaerobically by coupling
      hydrogen oxidation to the reduction of ferric iron. 

PMID- 24117602
TI  - Prediction of liver stiffness hepatocellular carcinoma in chronic hepatitis C
      patients on interferon-based anti-viral therapy.
AB  - BACKGROUND AND AIM: The purpose of this study was to evaluate the usefulness of
      liver stiffness measurement (LSM) for assessing the risk of hepatocellular
      carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN)
      therapy. METHODS: One hundred fifty-one CHC patients who underwent LSM and
      received IFN therapy were included in the estimation cohort, and 56 were included
      in the validation study. The cumulative HCC incidences were evaluated using
      Kaplan-Meier plot analysis and the log-rank test. Multivariate Cox proportional
      hazard analyses were used to estimate the hazard ratios (HRs) of variables for
      HCC. RESULTS: In the estimation cohort, 9 of 151 patients developed HCC during
      the median follow-up time of 722 days. Multivariate analysis identified three
      independent risk factors for HCC: LSM (>= 14.0 kPa, HR 5.58, P = 0.020), platelet
      count (< 14.1 * 10(4) /MUL, HR 5.59, P = 0.034), and non-sustained virological
      response (HR 8.28, P = 0.049). The cumulative incidence of HCC development at 3
      years was 59.6%, 8.2%, and 0.0% in patients with all three risk factors, one to
      two risk factors, and none of these risk factors, respectively. The incidence of
      HCC was significantly different between these groups (P < 0.001). In the
      validation cohort, HCC incidence was also significantly different with respect to
      these risk factors (P = 0.037). CONCLUSION: LSM, platelet count, and IFN
      therapeutic effect could be used to successfully stratify the risk of HCC in
      patients receiving IFN therapy and demonstrate the usefulness of LSM before IFN
      therapy for the management of CHC patients.

PMID- 24117603
TI  - Derivation of a short form of the Dentine Hypersensitivity Experience
      Questionnaire.
AB  - AIM: To derive and evaluate a short form of the Dentine Hypersensitivity
      Experience Questionnaire. METHODS: Data from three previous studies of dentine
      hypersensitivity (n = 353) were pooled and randomly divided into half. Ten- and
      15-item short forms were derived in the first half of the data using the item
      impact and regression methods. The four short forms were evaluated in the second
      half. RESULTS: The 10 and 15-item versions of the regression short form detected
      impacts in 37% and 61% of participants, respectively, compared to 68% and 93%
      using the item impact method. All short forms had internal consistency
      (Cronbach's alpha) >0.84 and test-retest reliability (ICC) >0.89. All correlated
      with the long form (all r > 0.93, p < 0.001) and with the effect of the mouth on
      everyday life (all r >= 0.73, p < 0.001). None of the short forms detected a
      treatment effect in two trials although all four showed a tendency to detect an
      effect in a trial where the long form had done so. CONCLUSIONS: The 15-item short
      form derived with the item impact method performed better than other short forms
      and appears to be sufficiently robust for use in individual patients.

PMID- 24117605
TI  - Observational etiologic research: part 2--effect measures in etiologic research.

PMID- 24117604
TI  - Five-year healthcare utilization and costs among lower-risk drinkers following
      alcohol treatment.
AB  - BACKGROUND: Lower-risk drinking is increasingly being examined as a treatment
      outcome for some patients following addiction treatment. However, few studies
      have examined the relationship between drinking status (lower-risk drinking in
      particular) and healthcare utilization and cost, which has important policy
      implications. METHODS: Participants were adults with alcohol dependence and/or
      abuse diagnoses who received outpatient alcohol and other drug treatment in a
      private, nonprofit integrated healthcare delivery system and had a follow-up
      interview 6 months after treatment entry (N = 995). Associations between past 30
      day drinking status at 6 months (abstinence, lower-risk drinking defined as
      nonabstinence and no days of 5+ drinking, and heavy drinking defined as 1 or more
      days of 5+ drinking) and repeated measures of at least 1 emergency department
      (ED), inpatient or primary care visit, and their costs over 5 years were examined
      using mixed-effects models. We modeled an interaction between time and drinking
      status to examine trends in utilization and costs over time by drinking group.
      RESULTS: Heavy drinkers and lower-risk drinkers were not significantly different
      from the abstainers in their cost or utilization at time 0 (i.e., 6 months
      postintake). Heavy drinkers had increasing odds of inpatient (p < 0.01) and ED (p
      < 0.05) utilization over 5 years compared with abstainers. Lower-risk drinkers
      and abstainers did not significantly differ in their service use in any category
      over time. No differences were found in changes in primary care use among the 3
      groups over time. The cost analyses paralleled the utilization results. Heavy
      drinkers had increasing ED (p < 0.05) and inpatient (p < 0.001) costs compared
      with the abstainers; primary care costs did not significantly differ. Lower-risk
      drinkers did not have significantly different medical costs compared with those
      who were abstinent over 5 years. However, post hoc analyses found lower-risk
      drinkers and heavy drinkers to not significantly differ in their ED use or costs
      over time. CONCLUSIONS: Performance measures for treatment settings that consider
      treatment outcomes may need to take into account both abstinence and reduction to
      nonheavy drinking. Future research should examine whether results are replicated
      in harm reduction treatment, or whether such outcomes are found only in
      abstinence-based treatment.

PMID- 24117606
TI  - Practitioner review: evidence-based practice guidelines on alcohol and drug
      misuse among adolescents: a systematic review.
AB  - BACKGROUND: Context-specific evidence-based guidelines on how to prevent and
      treat substance misuse among adolescents are currently lacking in many countries.
      Due to the time consuming nature of de novo guideline development, the ADAPTE
      collaboration introduced a methodology to adapt existing guidelines to a local
      context. An important step in this method is a systematic review to identify
      relevant high-quality evidence-based guidelines. This study describes the results
      of this step for the development of guidelines on adolescent alcohol and drug
      misuse in Belgium. METHODS: Rigorous systematic review methodology was used. This
      included searches of electronic databases (Medline, Embase, Cinahl, PsychInfo,
      and ERIC in June 2011), websites of relevant organizations, and reference lists
      of key publications. Experts in the field were also contacted. Included were
      Dutch, English, French, or German evidence-based practice guidelines from 2006 or
      later on the prevention, screening, assessment, or treatment of alcohol or
      illicit drug misuse in persons aged 12-18 years. Two independent reviewers
      assessed the quality of the guidelines using the AGREE II (Appraisal of
      Guidelines for Research and Evaluation) instrument. SCOPE: This overview provides
      a framework of current knowledge in adolescent alcohol and drug misuse prevention
      and treatment. RESULTS: This systematic review identified 32 relevant evidence
      based guidelines on substance misuse among adolescents. Nine guidelines were
      judged to be of high quality; of which four had recommendations specifically on
      adolescents: one on school-based prevention, one on substance misuse prevention
      in vulnerable young people and two on alcohol misuse with specific sections for
      the adolescent population. There were few commonalities as guidelines focused on
      different target groups, professional disciplines and type and level of substance
      misuse. Evidence to support the recommendations was sparse, and many
      recommendations were based on expert consensus or on studies among adults. Also,
      the link between evidence and recommendations was often unclear. CONCLUSIONS:
      There are a substantial number of guidelines addressing substance misuse in
      adolescents. However, only four high-quality guidelines included recommendations
      specific for adolescents. The current level of evidence that underpins the
      recommendations in these high-quality guidelines is low.

PMID- 24117607
TI  - Early childhood caries and associated determinants: a cross-sectional study on
      Italian preschool children.
AB  - OBJECTIVES: This study evaluates the influence of several determinants on the
      presence of early childhood caries (ECC) in preschool children living in northern
      Sardinia, Italy. These determinants include the educational level and
      occupational status of the parents as a proxy for the socioeconomical level (SES)
      and behavioral factors (dietary and oral hygiene). METHODS: An observational
      cross-sectional study was designed with a dental examination and a standardized
      questionnaire. Five hundred forty-four subjects (260 girls and 284 boys) were
      enrolled and categorized into two age groups: 359 children were aged 18-47 months
      and 185 children were aged 48-60 months. RESULTS: The total caries prevalence was
      15.99%. Caries risk increased with lower parents' educational level (P = 0.01),
      increased number of siblings (P < 0.01), the use of bottle feeding (P = 0.02),
      and the use of a sweetened baby's pacifier at night (P = 0.01). In robust
      multivariate analysis, a high parental educational level played a protective role
      on the presence of caries lesion [odds ratio (OR) = 0.51, 95% confidence interval
      (CI) 0.34-0.78]; the mother's being employed had a positive statistically
      significant association with the child having decayed, missing, filled tooth
      surfaces = 0 (OR = 0.64, 95% CI 0.23-0.97). The presence of more than one sibling
      in the family was associated with caries (OR = 1.70, 95% CI 1.20-2.40).
      CONCLUSION: ECC prevalence evaluated was similar to other western countries, and
      SES and behavioral habits influence the development of ECC.

PMID- 24117608
TI  - Early discontinuation of thyroxine therapy is possible in most very low
      birthweight infants with hypothyroidism detected by screening.
AB  - AIM: To determine the feasibility of discontinuing thyroid hormone treatment
      earlier than recommended by the current guidelines for congenital hypothyroidism.
      METHODS: We retrospectively reviewed the medical records of very low-birthweight
      (VLBW) infants born at Chungbuk National University Hospital from January 2006 to
      December 2010. Infants were divided into two groups--hypothyroid and normal
      thyroid--on the basis of the thyroid function test results. Infants in the
      hypothyroid group were treated with levothyroxine (L-T4) and attempts to
      discontinue this therapy began when they were about 2 years old. RESULTS: Of the
      216 infants born during the study period, 20 died and 196 were included in the
      study. Of these, 46 were in the hypothyroid group and 150 were in the normal
      thyroid group. Thirty-nine infants were taken off L-T4 therapy at around 2 years
      of age. All were successfully weaned off L-T4 and retained normal thyroid
      function. Tc-99 m thyroid scans were performed in 32 infants, and no distinct
      abnormality was noted. CONCLUSION: Thyroid dysfunction in VLBW infants was common
      in our cohort and most cases were transient. Attempts to discontinue this therapy
      could begin at around the age of two or earlier when low doses of L-T4 have
      achieved maintenance.

PMID- 24117609
TI  - Bark functional ecology: evidence for tradeoffs, functional coordination, and
      environment producing bark diversity.
AB  - The causes underlying bark diversity are unclear. Variation has been frequently
      attributed to environmental differences across sites. However, variation may also
      result from tradeoffs and coordination between bark's multiple functions. Bark
      traits may also covary with wood and leaf traits as part of major dimensions of
      plant variation. To assess hypotheses regarding tradeoffs and functional
      coordination, we measured bark traits reflecting protection, storage, mechanics,
      and photosynthesis in branches of 90 species spanning a wide phylogenetic and
      environmental range. We also tested associations between bark, wood, and leaf
      traits. We partitioned trait variation within species, and within and across
      communities to quantify variation associated with across-site differences. We
      observed associations between bark mechanics and storage, density and thickness,
      and thickness and photosynthetic activity. Increasing bark thickness contributed
      significantly to stiffer stems and greater water storage. Bark density, water
      content, and mechanics covaried strongly with the equivalent wood traits, and to
      a lesser degree with leaf size, xylem conductivity, and vessel diameter. Most
      variation was observed within sites and had low phylogenetic signal. Compared
      with relatively minor across-site differences, tradeoffs and coordination among
      functions of bark, leaves, and wood are likely to be major and overlooked factors
      shaping bark ecology and evolution. 

PMID- 24117610
TI  - Clear cell sarcoma of the tongue.

PMID- 24117611
TI  - The effects of recurrent episodes of depression on startle responses.
AB  - Prior work suggests that major depression is associated with abnormal startle
      blink responses; however, only chronic or recurrent depression appears to be
      associated with this effect. The current study tested this hypothesis directly by
      examining whether recurrent major depression accounted for the anomalous startle
      seen in major depression using a sample of 515 female twins from the Minnesota
      Twin Family Study. Blink responses recorded at the age of 20 were examined in
      relation to number of episodes of depression prospectively assessed from ages 11
      to 20. Results showed that only subjects who had experienced multiple episodes of
      depression showed abnormal startle responses. Subjects who had experienced just
      one episode of depression in their lifetime did not differ from controls. This
      lends additional support to the idea that recurrent depression may have a
      different etiological basis than nonrecurrent depression. 

PMID- 24117612
TI  - Upregulation of membrane-bound CD40L on CD4+ T cells in women with primary
      Sjogren's syndrome.
AB  - Epigenetic deregulation of genes encoded on the X chromosome as reported for
      CD40L in lupus could explain the female predominance of autoimmune diseases. We
      compared CD40L expression on CD4(+) T cells from primary Sjogren's syndrome (pSS)
      women and healthy controls and investigated DNA methylation patterns of the
      promoter and enhancer regions of CD40L. The expression of CD40L on activated
      CD4(+) T cells was higher in patients with pSS than controls after
      phorbolmyristate acetate and ionomycin activation (P = 0.02). CD40L mRNA level in
      CD4(+) T cells did not differ between patients with pSS and controls and was
      similar in both groups in cultures treated with the demethylating agent 5
      azacytidine C. Pyrosequencing analysis revealed no significant differences in
      methylation profiles between patients and controls. Inducible membrane-bound
      CD40L on CD4(+) T cells is increased in patients with pSS but was not related to
      epigenetic deregulation by demethylation patterns of the regulatory regions of
      CD40L.

PMID- 24117613
TI  - A neglected aspect of conscience: awareness of implicit attitudes.
AB  - The conception of conscience that dominates discussions in bioethics focuses
      narrowly on private regulation of behaviour resulting from explicit attitudes. It
      neglects to mention implicit attitudes and the role of social feedback in
      becoming aware of one's implicit attitudes. But if conscience is a way of
      ensuring that a person's behaviour is in line with her moral values, it must be
      responsive to all aspects of the mind that influence behaviour. There is a wealth
      of recent psychological work demonstrating the influence of implicit attitudes on
      behaviour. A necessary part of having a well-functioning conscience must thus be
      awareness and regulation of one's implicit attitudes in addition to one's
      explicit attitudes; this cannot be done by an individual in isolation. On my
      revised conception of conscience, heeding social feedback, being emotionally self
      aware and engaging in self-monitoring are important for the possession of a well
      functioning conscience. Health professionals may need specific training to help
      them develop and maintain a well-functioning conscience, which should involve
      cultivation of awareness of implicit attitudes, emphasis on social feedback and
      techniques to enable better control over them. 

PMID- 24117614
TI  - Food deprivation causes rapid changes in the abundance and glucidic composition
      of the cutaneous mucous cells of Atlantic salmon Salmo salar L.
AB  - Cutaneous mucus is the first physical and chemical barrier of fish. This slime
      layer is secreted by mucous cells located in the epidermis and is mainly composed
      of glycoproteins that have their origin in the diet. Therefore, food deprivation
      can potentially change the abundance and glucidic nature of skin mucous cells,
      thus changing the mucus properties. To test this hypothesis, we conducted an
      experiment with Atlantic salmon, Salmo salar L. Changes in the number and
      glucidic nature of epidermal mucus cells were analysed using standard techniques.
      The outcome of this study shows that food deprivation caused a rapid decrease in
      the density of epidermal mucous cells in Atlantic salmon. Lectin histochemistry
      revealed a change in the presence and stainability of some sugar residues in the
      mucous cells of unfed fish compared with fed fish. Given that the primary reason
      for mucus secretion in fish is for protection against infections, we speculate
      that the changes in the mucus properties caused by nutritional stress may affect
      their disease resistance. This fact is particularly important for fish that spend
      a period of time deprived of food, either as a part of their natural life cycle,
      or as part of farming practices. 

PMID- 24117615
TI  - Health and relationships with leisure time activities in Swedish children aged 2
      17 years.
AB  - BACKGROUND: Three cross-sectional time series studies, randomised and stratified
      for age and gender, were performed on children aged 2-17, studying their health
      and well-being. The studies were performed in the Nordic countries in 1984, 1996
      and 2011. Long-term illness (LTI) and psychosomatic complaints (PSC) increased
      during the period. Data were collected from mailed questionnaires. METHODS: Data
      of 1461 Swedish children from 2011 were used and compared with data from 1984 and
      1996. Relationships between the health indicators (the absence of LTI, 13
      diagnoses, the absence of PSC, six symptoms, six items of well-being) and 12
      activities were analysed. RESULTS: A total of 83.2% of the children were healthy
      and 16.8% had at least one LTI, boys 19.1% and girls 14.5%. PSC increased from
      18.6% in 1996 to 23.1% in 2011. The distribution was higher in girls. Girls were
      more active than boys during leisure time. 'Reading books', 'visiting friends',
      'listening to music' and 'activity in organisations' were related to an absence
      of PSC, LTI and well-being. 'Surfing/blogging on the Internet' was negatively
      related to LTI, PSC and well-being. Multiple regression showed that that 'visits
      or is visited by friends' was related with a low probability for LTI and also
      with a high probability for well-being. In the logistic regression analyses, the
      following variables were seen as promoting health most: 'visits or is visited by
      friends' and 'is active in organizations' for children aged 2-17 years,
      especially for boys and well-being. CONCLUSIONS: The health of Swedish children
      declined between 1984 and 2011. Positive relationships were found between some
      activities and health as well as other activities related to ill health. The
      results suggest an increased focus on the activities that have positive
      relationships with health in order to promote health among children.

PMID- 24117616
TI  - Patterns of microglial cell activation in frontotemporal lobar degeneration.
AB  - AIMS: Pathological heterogeneity within patients with frontotemporal lobar
      degeneration (FTLD) in general precludes the accurate assignment of diagnostic
      subtype in life. The aim of this study was to assess the extent of microglial
      cell activation in FTLD in order to determine whether it might be possible to
      employ this as a diagnostic marker in vivo using PET ligand [11C](R)-PK11195 in
      order to differentiate cases of FTLD according to histological subtype. METHODS:
      The distribution and extent of microglial cell activation was assessed semi
      quantitatively in cortical grey and subcortical white matter of CD68
      immunostained sections of frontal and temporal cortex from 78 pathologically
      confirmed cases of FTLD, 13 of Alzheimer's disease (AD) and 13 controls. RESULTS:
      Significantly higher levels of microglial cell activation than controls occurred
      in all four regions in FTLD, and in three of the four regions in AD. Microglial
      activation was greater in frontal subcortical white matter in FTLD than AD,
      whereas it was higher in temporal cortical grey matter in AD than FTLD.
      Microglial cell activation was significantly higher in temporal subcortical white
      matter in FTLD-MAPT than in other genetic (GRN, C9ORF72) or non-genetic forms of
      FTLD. CONCLUSIONS: The present study suggests that high levels of microglial cell
      involvement in temporal lobe (subcortical white matter) might serve as a marker
      of inherited FTLD associated with intronic mutations in MAPT, with a relatively
      intense signal in this region in PET studies using [11C](R)-PK11195 as microglial
      cell marker could indicate the presence of MAPT mutation in vivo.

PMID- 24117617
TI  - Lumbosacral abortive hemangioma with intradural extension.
AB  - Abortive hemangioma (AH) is a true hemangioma of infancy that expresses glucose
      transporter-1 protein in the endothelial cells, with an arrested growth cycle. We
      present the rare case of a lumbosacral AH with intramedullary extension. 

PMID- 24117618
TI  - Challenge-proven nonsteroidal anti-inflammatory drug hypersensitivity in
      children.
AB  - BACKGROUND: Few studies investigated hypersensitivity to nonsteroidal anti
      inflammatory drugs (NSAIDs) in children. The objective was to determine the
      frequency of true NSAID hypersensitivity (NSAID-H) and whether there were any
      parameters in the history of children that would predict NSAID-H. Secondly, an
      investigation was conducted into whether NSAID-hypersensitive children could
      tolerate safe alternatives. Differing from previous studies, the researchers
      followed the recent diagnostic algorithm proposed for acute reactions in NSAID-H.
      METHODS: Children with a history suggesting NSAID-H were evaluated by an
      allergist. The patients with a single NSAID in history were tested first with a
      skin prick test and if negative challenged with the culprit NSAID. The patients
      who had reactions with multiple NSAIDs were directly challenged with their
      culprit drugs. Safe alternatives in children with a confirmed NSAID-H were found
      by oral provocation tests (OPTs). RESULTS: Fifty-eight of 61 patients
      participated in the study. Thirty-eight patients (65.5%) described a reaction to
      a single NSAID and 20 mentioned reactions with >=2 different NSAIDs. Single-drug
      induced and cross-reactive NSAID-Hs were proven in 5 of 36 (14%) and 8 of 18
      (44%) of patients, respectively. Acetaminophen and nimesulide were tolerated in
      60% and 88.8% of the study patients as safe alternatives, respectively. Family
      history of NSAID-H was found as the only significant predictor of OPT (OR: 5.4;
      95% CI: 1.02-28.6). CONCLUSION: Histories of both single and multiple NSAID-Hs
      are poor predictors of actual drug hypersensitivity. Therefore, diagnostic tests
      should be performed in all children if no contraindication exits. Family history
      of NSAID-H is the only significant parameter predicting OPT results.

PMID- 24117619
TI  - The outcome of patients with oesophageal eosinophilic infiltration after an eight
      week trial of a proton pump inhibitor.
AB  - BACKGROUND: Current diagnostic guidelines recommend that eosinophilic
      oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of
      response to a trial of acid suppression. There is limited information available
      providing outcome data about the effectiveness of this approach. AIM: To examine
      the impact of double-dose proton pump inhibitor (PPI) therapy on symptoms,
      endoscopic and histological features in patients with documented oesophageal
      eosinophilia consistent with EoE (>=15 eosinophils/high-power field). METHODS:
      Sixty consecutive symptomatic patients with documented oesophageal eosinophilia
      received open-label omeprazole 20 mg orally twice daily before meals for 8 weeks.
      Clinical, endoscopic and histological (resolution: 0-5 eosinophils/HPF, partial
      improvement: 5-14 eosinophils/HPF), or no improvement: (>=15 eosinophils/HPF)
      evaluation was repeated at the end of this period. An expert GI pathologist,
      unaware of the study aims, reviewed all slides. RESULTS: Clinical improvement
      occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and
      normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%)
      obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete
      clinical and histological remission. CONCLUSIONS: More than 50% of patients with
      documented oesophageal eosinophilic infiltration in the EoE range improved when
      treated with a double-dose PPI trial for 8 weeks. These findings support the
      published guidelines recommending a PPI trial prior to diagnosing EoE, and
      confirm the existence of an eosinophilic oesophageal infiltrationPPI-responsive
      population.

PMID- 24117620
TI  - Early elevation of albumin excretion rate is associated with poor gluten-free
      diet adherence in young people with coeliac disease and diabetes.
AB  - AIMS: There are conflicting data on microvascular complications in coexisting
      Type 1 diabetes and coeliac disease. We compared complications rates in youth
      with or without coeliac disease and examined the association between gluten-free
      diet adherence and complications. METHODS: This was a comparative study of
      adolescents (2510 without coeliac disease, 129 with coeliac disease); 60 (47%)
      did not adhere to a gluten-free diet--defined as elevated anti-tissue
      transglutaminase or endomysial immunoglobulin A titres. Retinopathy was detected
      using 7-field fundal photography and albumin excretion rate by timed overnight
      urine collections, with early elevation defined as albumin excretion rate >= 7.5
      MUg/min. Logistic regression was used to examine the association between
      complications and explanatory variables, including coeliac disease vs. no coeliac
      disease, gluten-free diet adherence vs. non-adherence, diabetes duration and
      HbA1c . RESULTS: Median age at last assessment was 16.5 years. Those with coeliac
      disease vs. those without were younger at diabetes diagnosis (7.1 vs. 8.6 years,
      P < 0.001) and had longer diabetes duration (9.3 vs. 7.2 years, P < 0.001). HbA1c
      was lower in those with coeliac disease vs. those without (67 vs. 70 mmol/mol,
      8.3 vs. 8.6%, P = 0.04) and adherence to a gluten-free diet vs. non-adherence (66
      vs. 72 mmol/mol, 8.2 vs. 8.7%, P = 0.003). There were no differences in
      complication rates between those with coeliac disease vs. those without
      (retinopathy 22 vs. 23%, elevated albumin excretion rate 31 vs. 28%). Non
      adherence to a gluten-free diet was associated with elevated albumin excretion
      rate (40 vs. 23%, P = 0.04). In multivariable logistic regression, elevated
      albumin excretion rate was associated with non-adherence to a gluten-free diet
      (odds ratio 2.37, 95% CI 1.04-5.40, P = 0.04) and diabetes duration (odds ratio
      1.13, 95% CI 1.02-1.25, P = 0.03), but not HbA1c . CONCLUSIONS: While glycaemic
      control is better in patients with coeliac disease, non-adherence to a gluten
      free diet is associated with elevated albumin excretion rate. The possible
      protection of a gluten-free diet on complications warrants further investigation.

PMID- 24117621
TI  - Seventeen-year study shows rise in parapneumonic effusion and empyema with higher
      treatment failure after chest tube drainage.
AB  - AIM: To evaluate epidemiology, pre-admission characteristics and management of
      paediatric parapneumonic effusions (PPEs) and empyema in a tertiary paediatric
      pulmonary centre between 1993 and 2010. METHODS: Retrospective chart review study
      using paediatric and thoracic database searches, with particular emphasis on pre
      admission characteristics, disease stage (simple or complex effusion or empyema),
      general management and surgical procedures. RESULTS: One hundred children were
      eligible, exhibiting a significant increase in incidence from 0.5 to 2.6 per 100
      000 across the study period. Baseline characteristics were similar across disease
      stages. Streptococcus pneumoniae was the most common pathogen. Surgical
      intervention beyond chest tube drainage (CTD) was required in 50%; this rate
      showed a particular increase in children aged 0-5 years (OR, 3.1), but was
      otherwise not influenced by baseline characteristics, disease stage or use of
      intrapleural fibrinolytics. Length of hospitalisation did not differ across
      disease stages or primary interventional procedures. CONCLUSION: This study
      confirmed an increasing incidence of PPEs and empyema in a Scandinavian tertiary
      paediatric pulmonary centre. Young children exhibited higher treatment failure
      after CTD. Length of hospitalisation was similar across disease stages and was
      comparable to previous reports according to primary interventional procedure.

PMID- 24117622
TI  - Quantitation of fetal heart function with tissue Doppler velocity imaging
      reference values for color tissue Doppler velocities and comparison with pulsed
      wave tissue Doppler velocities.
AB  - Quantitative assessment of fetal heart function has been difficult. Increasingly,
      tissue Doppler imaging (TDI) is used to measure fetal cardiac function
      noninvasively. There are two principal techniques, spectral pulsed wave (PW) TDI
      and color TDI (CTDI). Published reference values for fetal myocardial velocities
      are based on spectral PW TDI only. However, previous phantom, adult, and animal
      studies have shown that PW TDI velocities are systematically higher than CTDI
      velocities. There are no fetal studies so far. We hypothesized that myocardial
      velocities derived by PW TDI and CTDI are significantly different in the fetus.
      This prospective observational study included 91 fetuses (gestational age 28.6 +/
      6.6 weeks; range 19-40 weeks) seen for routine prenatal ultrasound. From apical
      4-chamber views, tricuspid ring (right ventricle), lateral and septal mitral ring
      were sampled by PW TDI and CTDI. Bland-Altman analysis was used for comparisons.
      PW and CTDI S' velocities correlated strongly in all three cardiac segments (r =
      0.6 to 0.9; P < 0.01). There was a systematic bias toward higher velocities with
      PW TDI versus CTDI (bias 0.96 cm/s; 95% CI 1.08-0.85 cm/s). However, the strength
      of the correlation and bias varied depending on the region of the fetal heart
      sampled. PW TDI and CTDI velocity measurements are feasible in the fetus and
      correlate well. However, PW TDI velocities are higher than CTDI velocities with
      significant regional variation. This precludes a mathematical conversion of PW to
      CTDI in vivo. As PW TDI and color TDI vary, different reference values for fetal
      CTDI velocities were generated. 

PMID- 24117623
TI  - A lipid neurochemist's siren: docosahexaenoic acid and its elusive function in
      the central nervous system.

PMID- 24117624
TI  - A safer method for body restoration following autopsy.
AB  - Restoration of autopsy incisions can result in inadvertent needle stick injury to
      the prosector, which can be difficult to prevent even with the use of personal
      protective equipment such as Kevlar cut resistant gloves. We present a new
      technique for closure of autopsy incisions using a commonly available commercial
      hardware tool, a hole punch with a lever enhanced action, combined with blunt
      probe sewing, which results in an esthetic and leak-proof means of restoring
      cadavers. This technique is especially useful in cases which may pose blood-borne
      infection risks to the prosector. 

PMID- 24117626
TI  - Observational etiologic research: part 1--The etiologic research question: it
      requires DATA.

PMID- 24117625
TI  - KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein
      kinase Mzeta.
AB  - The WWC1 gene has been genetically associated with human episodic memory
      performance, and its product KIdney/BRAin protein (KIBRA) has been shown to
      interact with the atypical protein kinase protein kinase M zeta (PKMzeta).
      Although recently challenged, PKMzeta remains a candidate postsynaptic regulator
      of memory maintenance. Here, we show that PKMzeta is subject to rapid proteasomal
      degradation and that KIBRA is both necessary and sufficient to counteract this
      process, thus stabilizing the kinase and maintaining its function for a prolonged
      time. We define the binding sequence on KIBRA, a short amino acid motif near the
      C-terminus. Both hippocampal knock-down of KIBRA in rats and KIBRA knock-out in
      mice result in decreased learning and memory performance in spatial memory tasks
      supporting the notion that KIBRA is a player in episodic memory. Interestingly,
      decreased memory performance is accompanied by decreased PKMzeta protein levels.
      We speculate that the stabilization of synaptic PKMzeta protein levels by KIBRA
      may be one mechanism by which KIBRA acts in memory maintenance. KIBRA/WWC1 has
      been genetically associated with human episodic memory. KIBRA has been shown to
      be post-synaptically localized, but its function remained obscure. Here, we show
      that KIBRA shields PKMzeta, a kinase previously linked to memory maintenance,
      from proteasomal degradation via direct interaction. KIBRA levels in the rodent
      hippocampus correlate closely both to spatial memory performance in rodents and
      to PKMzeta levels. Our findings support a role for KIBRA in memory, and unveil a
      novel function for this protein. 

PMID- 24117627
TI  - Distinct human T-lymphocyte responses triggered by Porphyromonas gingivalis
      capsular serotypes.
AB  - AIM: Porphyromonas gingivalis can synthesize an extracellular capsule and
      different serotypes have been described based on capsular antigenicity. On
      dendritic cells (DCs), the type of capsule present plays a role on the strength
      of the developed immune response. This study aimed to investigate the T
      lymphocyte responses when stimulated with autologous mature DCs exposed to
      different P. gingivalis K-serotypes. MATERIALS AND METHODS: Naive CD4(+) T
      lymphocytes were obtained from healthy subjects and stimulated with autologous
      DCs primed with increasing multiplicity of infections of the different P.
      gingivalis K-serotypes. The Th1, Th2, Th17 and T-regulatory cytokines and
      transcription factor levels were quantified. RESULTS: Distinct types of response
      were detected when T-lymphocytes were stimulated by DCs primed with the different
      P. gingivalis K-serotypes. T-lymphocytes stimulated by K1 or K2-primed DCs
      elicited higher levels of Th1 and Th17-associated cytokines, T-bet and RORC2 than
      T-lymphocytes stimulated with DCs primed with the other serotypes. Conversely,
      the serotypes K3-K5 induced higher levels of Th2-associated cytokines and GATA-3
      than the others. CONCLUSIONS: These results demonstrate that DCs primed with the
      different P. gingivalis K-serotypes elicited distinct T-cell responses. Strains
      K1 (W83) and K2 (HG184) induced a Th1/Th17 pattern of immune response and K3
      (A7A1-28), K4 (ATCC((r)49417TM) ), and K5 (HG1690) a Th2 response.

PMID- 24117628
TI  - Assessment of parental oral health knowledge and behaviors among American Indians
      of a Northern Plains tribe.
AB  - OBJECTIVES: Investigate the relationship between sociodemographic variables and
      oral health knowledge and behaviors of American Indian (AI) parents as the
      initial step in a program aimed at reducing caries experience among AI children.
      METHODS: Survey data were collected from a sample of 147 AI parents of children
      ages 0-7 years who are residents of a Northern Plains reservation. Questions
      addressed sociodemographic variables for parents/their children and parent oral
      health knowledge and behavior. Overall knowledge was measured as percentage of
      items answered correctly. Overall behavior was measured as percentage of items
      reflecting behavior consistent with accepted oral health recommendations. Oral
      health knowledge and behaviors, and the relationship between them, were evaluated
      across groups defined by quartiles. RESULTS: Parent sociodemographic variables
      were not significantly associated with behavior scores. Female gender, higher
      level of education, and higher income were significantly and positively
      associated with mean knowledge scores. Behavior and knowledge scores were
      significantly correlated. On average, survey participants identified the best
      answer for 75 percent of knowledge items and engaged in 58 percent of optimal
      oral health behaviors. Participants in higher oral health knowledge quartiles had
      greater adherence with recommended oral health behaviors than those in lower
      quartiles. CONCLUSIONS: Surveyed AI parents had reasonably high levels of
      knowledge about oral health and caries prevention for their children but engaged
      at relatively lower levels in parental behaviors necessary to promote oral
      health. Strategies focused on behavior change, rather than knowledge alone, may
      be most likely to affect oral health outcomes for AI children.

PMID- 24117629
TI  - Does urbanization shape bacterial community composition in urban park soils? A
      case study in 16 representative Chinese cities based on the pyrosequencing
      method.
AB  - Although the geographical distribution patterns of microbes have been studied for
      years, few studies have focused on urban soils. Urbanization may have detrimental
      effects on the soil ecosystem through pollution discharge and changes in urban
      climate. It is unclear whether urbanization-related factors have any effect on
      soil bacterial communities. Therefore we investigated geographical patterns of
      soil microbial communities in parks in 16 representative Chinese cities. The
      microbial communities in these 95 soil samples were revealed by 454
      pyrosequencing. There were 574,442 effective sequences among the total of 980,019
      16S rRNA gene sequences generated, showing the diversity of the microbial
      communities. Proteobacteria, Actinobacteria, Acidobacteria, Planctomycetes,
      Chloroflexi and Bacteroidetes were found to be the six dominant phyla in all
      samples. Canonical correspondence analysis showed that pH, followed by annual
      average precipitation, annual average temperature, annual average relative
      humidity and city sunshine hours, Mn and Mg were the factors most highly
      correlated with the bacterial community variance. Urbanization did have an effect
      on bacterial community composition of urban park soils but it contributed less to
      the total variance compared with geographical locations and soil properties,
      which explained 6.19% and 16.78% of the variance, respectively.

PMID- 24117630
TI  - Neurogenic [corrected] and oropharyngeal dysphagia.
AB  - Oropharyngeal dysphagia (OD) is a swallowing disorder caused by congenital
      abnormalities and structural damage and disease-associated damage of the oral
      cavity, pharynx, and upper esophageal sphincter. Patients with OD lack the
      protective mechanisms necessary for effective swallowing, exhibiting difficulty
      controlling food in the mouth and initiating a swallow, leading to choking,
      coughing, and nasal regurgitation. OD is a major risk factor for malnutrition,
      dehydration, and aspiration pneumonia. The following on OD includes commentaries
      on the application of simulation of oropharyngeal transient receptor potential
      vanilloid 1 (TRPV1) and maneuvers like the Shaker exercise to improve the safety
      and efficacy of swallow in OD patients; the prevalence of esophageal pathologies
      in OD patients and the need to evaluate the esophagus, esophagogastric junction,
      and stomach; and strategies for clinical screening to detect OD and aspiration
      among high-risk patients and to improve oral health care, maintain nutrition and
      hydration, and prevent aspiration pneumonia. 

PMID- 24117631
TI  - Innovative techniques in evaluating the esophagus; imaging of esophageal
      morphology and function; and drugs for esophageal disease.
AB  - This paper reporting on techniques for esophageal evaluation and imaging and
      drugs for esophageal disease includes commentaries on endoscopy techniques
      including dye-based high-resolution and dye-less high-definition endoscopy; the
      shift from CT to MRI guidance in tumor delineation for radiation therapy; the
      role of functional lumen imaging in measuring esophageal distensibility;
      electrical stimulation of the lower esophageal sphincter (LES) as an alternative
      to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the
      morphological findings of reflux esophagitis and esophageal dysmotility on double
      contrast esophagography; the value of videofluoroscopy in assessing protecting
      mechanisms in patients with chronic reflux or swallowing disorders; targeting
      visceral hypersensitivity in the treatment of refractory GERD; and the symptoms
      and treatments of nighttime reflux and nocturnal acid breakthrough (NAB). 

PMID- 24117632
TI  - Outcomes of esophageal surgery, especially of the lower esophageal sphincter.
AB  - This paper includes commentaries on outcomes of esophageal surgery, including the
      mechanisms by which fundoduplication improves lower esophageal sphincter (LES)
      pressure; the efficacy of the LinxTM management system in improving LES function;
      the utility of radiologic characterization of antireflux valves following
      surgery; the correlation between endoscopic findings and reported symptoms
      following antireflux surgery; the links between laparoscopic sleeve gastrectomy
      and decreased LES pressure, endoscopic esophagitis, and gastroesophageal reflux
      disease (GERD); the less favorable outcomes following fundoduplication among
      obese patients; the application of bioprosthetic meshes to reinforce hiatal
      repair and decrease the incidence of paraesophageal hernia; the efficacy of
      endoluminal antireflux procedures, and the limited efficacy of revisional
      antireflux operations, underscoring the importance of good primary surgery and
      diligent work-up to prevent the necessity of revisional procedures. 

PMID- 24117633
TI  - Respiratory manifestations of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is highly associated with a range of
      respiratory symptoms, arising from a variety of etiologies. The following
      commentaries on respiratory manifestations of GERD address evidence for a role of
      a vagally mediated bronchoconstriction reflex in the development of asthma; the
      direct effects of airway obstruction on lower esophageal sphincter (LES) pressure
      and reflux episodes; the mechanisms by which reflux may play roles in chronic
      cough and airway stenosis; the limited efficacy of laparoscopic antireflux
      surgery (LARS) in improving GERD-related respiratory symptoms; the search for a
      marker for microaspiration and reflux-induced airway disease; and the potential
      of proton pump inhibitor (PPI) treatment for patients presenting with asthma and
      GERD. 

PMID- 24117634
TI  - The neurophysiology of the esophagus.
AB  - This paper reports on the neurophysiology of the esophagus, including on the
      uneven distribution of innervation in the esophagus, reflected by the increased
      sensitivity and perception of gastroesophageal reflux disease (GERD) events in
      the proximal rather than distal esophagus; the role of the enteric nervous system
      (ENS) in swallowing; the role of the physiological stress-responsive systems,
      including the autonomic nervous system (ANS) and the hypothalamic-pituitary
      adrenal (HPA) axis in mediating esophageal pain; the advances in understanding
      pain mechanisms and brain structure provided by technological imaging advances;
      investigations into the efficacy of the descending-pain control system, including
      diffuse noxious inhibitory control (DNIC); the role of abnormal nervous signaling
      in afferent pathways in the pathogenesis of Barrett's esophagus (BE); and the
      contribution of the esophageal mucosa to reflux symptoms. 

PMID- 24117635
TI  - Laryngopharyngeal reflux and GERD.
AB  - In patients with laryngopharygeal reflux (LPR), gastric contents exhibit
      retrograde flow into the upper aero-digestive tract, causing extraesophageal
      symptoms including chronic cough, hoarseness, indigestion, difficulty swallowing,
      globus pharyngis, and asthma. The following on laryngopharyngeal reflux includes
      commentaries on the use of patient-completed questionaires and anti-human pepsin
      antibodies and other non-invasive tests in diagnosis; the role of pepsin and acid
      in the etiologies of laryngeal cancers; and the application of proton pump
      inhibitor (PPI) therapy for the treatment of LPR. 

PMID- 24117636
TI  - Gastrointestinal sensitivity and gastroesophageal reflux disease.
AB  - This paper reports on gastrointestinal sensitivity, including on the role of
      refluxate volume on the perception of reflux symptoms; experimental pain models
      that mimic mechanisms and symptoms of pain associated with esophageal diseases;
      the potential role of the acid receptor TRPV1 in the genesis of gastroesophageal
      reflux disease (GERD) symptoms; and roles for ATP and the purine and pyrimidine
      receptor subfamilies P1, P2X, and P2Y in the pathogenesis of GERD symptoms. 

PMID- 24117637
TI  - Nonspecific motility disorders, irritable esophagus, and chest pain.
AB  - This paper presents commentaries on whether Starling's law applies to the
      esophagus; whether erythromycin affects esophageal motility; the relationship
      between hypertensive lower esophageal sphincter and vigorous achalasia; whether
      ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor
      disorders; health care and epidemiology of chest pain; whether normal pH excludes
      esophageal pain; the role of high-resolution manometry in noncardiac chest pain;
      whether pH-impedance should be included in the evaluation of noncardiac chest
      pain; whether there are there alternative therapeutic options to PPI for treating
      noncardiac chest pain; and the usefulness of psychological treatment and
      alternative medicine in noncardiac chest pain. 

PMID- 24117638
TI  - Causes, evaluation, and consequences of eosinophilic esophagitis.
AB  - This paper presents commentaries on whether eosinophilic esophagitis is a food
      allergy; inflammation in the context of eosinophilic esophagitis; whether
      eosinophilic esophagitis a cause of noncardiac chest pain; the role of endoscopy
      in the evaluation of eosinophilic esophagitis; and whether response to proton
      pump inhibitor therapy can distinguish eosinophilic esophagitis from
      gastroesophageal reflux disease. 

PMID- 24117639
TI  - Stents for benign and malignant esophageal strictures.
AB  - This paper presents commentaries on endotherapy for esophageal perforation/leaks;
      treatment of esophageal perforation; whether esophageal stents should be used for
      treating benign esophageal strictures; what determines the optimal stenting
      period in benign esophageal strictures/leaks; how to choose an esophageal stent;
      how a new fistula secondary to an esophageal stent should be treated; which
      strategy should be adopted when a fistula of a cervical anastomosis occurs;
      intralesional steroids for refractory esophageal strictures; balloon and bougie
      dilators for esophageal strictures and predictors of response to dilation;
      whether refractory strictures from different etiologies respond differently to
      endotherapy; surgical therapy of benign esophageal strictures; and whether
      stenoses following severe esophageal burns should be treated by esophageal
      resection or esophageal bypass. 

PMID- 24117640
TI  - The esophageal mucosa and submucosa: immunohistology in GERD and Barrett's
      esophagus.
AB  - This paper presents commentaries on the microscopic morphology of esophageal
      squamous epithelium; the frequency of duplication of the muscularis mucosae (MM)
      in Barrett's esophagus (BE); the significance of multilayered epithelium; whether
      cells in the lamina propria reflect those in the epithelium; how stem cells are
      identified in the squamous esophagus; dilated intercellular spaces; the
      metastasizing potential of early carcinoma-dependent, molecular or
      immunohistochemical tests that improve diagnosis; the role of
      immunohistochemistry IHC in grading of neoplasia in Barrett's esophagus and
      defining the risk of progression to adenocarcinoma; the roles of CDX1 and CDX2 in
      squamous and cardiac mucosa; and the role of desmosomal cadherins and lectins in
      squamous and cardiac mucosa. 

PMID- 24117641
TI  - Endotherapy for and tailored approaches to treating GERD, and refractory GERD.
AB  - This paper presents commentaries on how endoluminal antireflux procedures compare
      to laparoscopic fundoplication; new endoscopic procedures being studied to treat
      refractory gastroesophageal reflux disease (GERD); the new Stretta; the
      relationship between obesity and proton pump inhibitor (PPI) resistance; data
      concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing
      refractory GERD; whether microscopic esophagitis is relevant in determining
      symptoms of non-erosive reflux disease (NERD); how concomitant functional
      gastrointestinal disorders affect the PPI response in NERD; the evidence that a
      functional esophagus is associated with inflammatory bowel syndrome (IBS); the
      role of GABA agonists in the treatment of refractory GERD; the role of
      biofeedback and antidepressants in refractory GERD; and endoluminal
      fundoplication using the EsophyX device. 

PMID- 24117642
TI  - Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal
      adenocarcinoma.
AB  - This paper presents commentaries on animal models used for Barrett's esophagus
      (BE) and esophageal adenocarcinoma (EAC) research; acid- and bile-induced
      chromosomal instability and clonal selection during the progression of BE to EAC;
      how the components of gastric refluxate, especially acid and bile salts, promote
      carcinogenesis in metaplastic BE; genome-wide changes in DNA methylation and
      transcription involved in BE carcinogenesis; the potential role of miRNA in the
      development of BE and EAC; the effect of inflammatory cytokines linked to obesity
      on the activation of cell-death pathways and cell survival in BE and esophageal
      cancer; and the role of autophagy in esophageal cancer development. 

PMID- 24117643
TI  - Tissue resistance in the normal and diseased esophagus.
AB  - This paper presents commentaries on reflux-induced injury of human esophageal
      epithelium; inflammation in human reflux esophagitis; motor consequences of
      reflux-induced inflammation in esophageal epithelium; the microscopic morphology
      of esophageal squamous epithelium; intraluminal impedance in the evaluation of
      the esophageal mucosa; endoscopic tissue morphology of esophageal squamous
      epithelium; and the developmental biology of esophageal squamous epithelium. 

PMID- 24117644
TI  - New therapeutic strategies for squamous cell cancer and adenocarcinoma.
AB  - This paper presents commentaries on neoadjuvant treatment esophagectomy; the
      prognostic and predictive effects of single nucleotide polymorphisms (SNP) in the
      multimodality therapy of esophageal cancer; optimal preoperative treatment prior
      to surgery for esophageal cancer; a possible role for trastuzumab in treating
      esophageal adenocarcinoma or any esophageal dysplasia/intra-epithelial neoplasia;
      surgery after chemoradiation in resectable esophageal cancer; whether para-aortic
      lymph node dissection should be performed in esophagogastric junction (EGJ)
      tumors; and transhiatal esophagectomy in treatment of the esophageal cancer. 

PMID- 24117645
TI  - Functional testing: pharyngeal pH monitoring and high-resolution manometry.
AB  - The following paper on functional testing of the pharynx includes commentaries on
      the use of 24-h pH-impedance testing to identify patients with nonacid reflux and
      the caveats associated with automatic and visual analysis; the potential
      diagnostic yield of ambulatory high-resolution manomentry (HRM), particularly in
      identifying non-cardiac chest pain and transient lower esophageal sphincter
      relaxations; the differential manometric identification of conditions facilitated
      by using solid swallows, and the advantages of the newly developed ResTech
      oropharyngeal pH probe in the detection of proximal reflux events. 

PMID- 24117646
TI  - Causes and treatments of achalasia, and primary disorders of the esophageal body.
AB  - The following on achalasia and disorders of the esophageal body includes
      commentaries on controversies regarding whether patients with complete lower
      esophageal sphincter (LES) relaxation can be considered to exhibit early
      achalasia; the roles of different mucle components of the LES in achalasia;
      sensory neural pathways impaired in achalasia; indications for peroral endoscopic
      myotomy and advantages of the technique over laparoscopic and thorascopic
      myotomy; factors contributing to the success of surgical therapy for achalasia;
      modifications to the classification of esophageal body primary motility disorders
      in the advent of high-resolution manometry (HRM); analysis of the LES in
      differentiating between achalasia and diffuse esophageal spasm (DES); and
      appropriate treatment for DES, nutcracker esophagus (NE), and hypertensive LES
      (HTLES). 

PMID- 24117647
TI  - Upper esophageal sphincter dysfunction: diverticula-globus pharyngeus.
AB  - The following discussion of upper esophageal sphincter dysfunction includes
      commentaries on the role of the cricopharyngeus muscle in reflux disease; the
      etiology and treatment of Zenker diverticulum; the use of videofluoroscopy in
      patients with dysphagia, suspicion of aspiration, or globus; the role of pH
      impedance monitoring in globus evaluation; and treatment for reflux-associated
      globus. 

PMID- 24117648
TI  - Physiology of the upper segment, body, and lower segment of the esophagus.
AB  - The following discussion on the physiology of the esophagus includes commentaries
      on the function of the muscularis mucosa and submucosa as a mechanical antireflux
      barrier in the esophagus; the different mechanisms of neurological control in the
      esophageal striated and smooth muscle; new insights from animal models into the
      neurotransmitters mediating lower esophageal sphincter (LES) relaxation,
      peristalsis in the esophageal body (EB), and motility of esophageal smooth
      muscle; differentiation between in vitro properties of the lower esophageal
      circular muscle, clasp muscle, and sling fibers; alterations in the relationship
      between pharyngeal contraction and relaxation of the upper esophageal sphincter
      (UES) in patients with dysphagia; the mechanical relationships between anterior
      hyoid movement, the extent of upper esophageal opening, and aspiration; the
      application of fluoroscopy and manometry with biomechanics to define the stages
      of UES opening; and nonpharmacological approaches to alter the gastroesophageal
      junction (GEJ). 

PMID- 24117649
TI  - Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's
      esophagus.
AB  - The following paper on gastroesophageal reflux disease (GERD) and Barrett's
      esophagus (BE) includes commentaries on defining esophageal landmarks; new
      techniques for evaluating upper esophageal sphincter (UES) tone; differential
      diagnosis of GERD, BE, and hiatal hernia (HH); the use of high-resolution
      manometry for evaluation of reflux; the role of fundic relaxation in reflux; the
      use of 24-h esophageal pH-impedance testing in differentiating acid from nonacid
      reflux and its potential inclusion in future Rome criteria; classification of
      endoscopic findings in GERD; the search for the cell origin that generates BE;
      and the relationship between BE, Barrett's carcinoma, and obesity. 

PMID- 24117650
TI  - Barrett's esophagus: cancer and molecular biology.
AB  - The following paper on the molecular biology of Barrett's esophagus (BE) includes
      commentaries on signaling pathways central to the development of BE including Hh,
      NF-kappaB, and IL-6/STAT3; surgical approaches for esophagectomy and
      classification of lesions by appropriate therapy; the debate over the merits of
      minimally invasive esophagectomy versus open surgery; outcomes for patients with
      pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and
      chemoradiotherapy; animal models examining the surgical models of BE and
      esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and
      the use of in vitro BE models for chemoprevention studies. 

PMID- 24117652
TI  - Profiling functions of ectomycorrhizal diversity and root structuring in
      seedlings of Norway spruce (Picea abies) with fast- and slow-growing phenotypes.
AB  - We studied the role of taxonomical and functional ectomycorrhizal (ECM) fungal
      diversity in root formation and nutrient uptake by Norway spruce (Picea abies)
      seedlings with fast- and slow-growing phenotypes. Seedlings were grown with an
      increasing ECM fungal diversity gradient from one to four species and sampled
      before aboveground growth differences between the two phenotypes were apparent.
      ECM fungal colonization patterns were determined and functional diversity was
      assayed via measurements of potential enzyme activities of eight exoenzymes
      probably involved in nutrient mobilization. Phenotypes did not vary in their
      receptiveness to different ECM fungal species. However, seedlings of slow-growing
      phenotypes had higher fine-root density and thus more condensed root systems than
      fast-growing seedlings, but the potential enzyme activities of ectomycorrhizas
      did not differ qualitatively or quantitatively. ECM species richness increased
      host nutrient acquisition potential by diversifying the exoenzyme palette. Needle
      nitrogen content correlated positively with high chitinase activity of
      ectomycorrhizas. Rather than fast- and slow-growing phenotypes exhibiting
      differing receptiveness to ECM fungi, our results suggest that distinctions in
      fine-root structuring and in the belowground growth strategy already apparent at
      early stages of seedling development may explain later growth differences between
      fast- and slow-growing families. 

PMID- 24117653
TI  - Longitudinal associations between breastfeeding and observed mother-child
      interaction qualities in early childhood.
AB  - BACKGROUND: Despite extensive literature on the role of breastfeeding in maternal
      and child health and cognitive development, few studies have systematically
      tested whether breastfeeding predicts children's socio-emotional outcomes. The
      present study examined associations between trajectories of breastfeeding and
      observed parent-child interaction qualities of maternal sensitivity, child
      positivity, and child negativity from 6 months to 3 years of age. METHODS: Data
      were drawn from the NICHD Study of Early Child Care and Youth Development (n =
      1306 US families). Hierarchical linear modelling accounted for demographic and
      early characteristics, including home environment, maternal depression, and
      observed global relationship quality. RESULTS: Breastfeeding was associated with
      increases in observed maternal sensitivity over time, even after the effects of
      demographic and early characteristics were controlled. Accounting for the
      covariates, breastfeeding was not associated with child behaviour (i.e.
      positivity, negativity) in mother-child interaction across early childhood.
      CONCLUSIONS: Improved relationship quality, specifically through changes in
      maternal behaviour, may be another advantage experienced by breastfeeding mothers
      and children.

PMID- 24117654
TI  - Impact of IL28B polymorphisms on 24-week telaprevir-based combination therapy for
      Asian chronic hepatitis C patients with hepatitis C virus genotype 1b.
AB  - BACKGROUND AND AIM: The aim of this study was to clarify which or how factors
      could influence the probability of sustained virological response (SVR) in 24
      week telaprevir-based triple combination therapy for East Asian chronic hepatitis
      C patients infected with hepatitis C virus genotype 1b. METHODS: Of 140 patients
      who were enrolled in this study, 137 received 12-week telaprevir combined with 24
      week pegylated interferon alpha-2b plus ribavirin and were subjected to the
      analysis. Factors associated with SVR were analyzed by multiple logistic
      regression analysis. RESULTS: Of the 137 patients, 112 (82%) achieved SVR. Of 87
      patients with IL28B single nucleotide polymorphism rs8099917 genotype TT, 84
      (97%) achieved SVR. By contrast, 28 of 50 (56%) patients with the genotype TG/GG
      had SVR (P = 3.29 * 10(-9) ). Fifty-three of 60 (88%) naive patients and 50 of 54
      (93%) prior relapsers achieved SVR. Nine of 13 (69%) prior partial responders and
      none of 10 (0%) prior null responders achieved SVR. Multivariable analysis
      identified four independent factors that were significantly associated with SVR:
      IL28B SNP rs8099917 genotype (P = 6.90 * 10(-5) ), pre-existence of cirrhosis (P
      = 3.99 * 10(-3) ), prior treatment response (P = 0.0126), and rapid virological
      response (P = 0.0239). CONCLUSIONS: The IL28B single nucleotide polymorphism
      still remained informative as a predictor of SVR to 24-week telaprevir-based
      triple combination therapy for East Asian patients infected with hepatitis C
      virus genotype 1b.

PMID- 24117655
TI  - Are we drunk yet? Motor versus cognitive cues of subjective intoxication.
AB  - BACKGROUND: Perception of alcohol intoxication presumably plays an important role
      in guiding behavior during a current drinking episode. Yet, there has been
      surprisingly little investigation of what aspects associated with intoxication
      are used by individuals to attribute their level of intoxication. METHODS:
      Building on recent laboratory-based findings, this study employed a complex field
      based design to explore the relative contributions of motor performance versus
      cognitive performance-specifically executive control-on self-attributions of
      intoxication. Individuals recruited outside of bars (N = 280; mean age = 22;
      range: 18 to 32) completed a structured interview, self-report questionnaire, and
      neuropsychological testing battery, and provided a breath alcohol concentration
      (BrAC) sample. RESULTS: Results of a multiple linear regression analysis
      demonstrated that current level of subjective intoxication was associated with
      current alcohol-related stimulant effects, current sedative effects, and current
      BrAC. After controlling for the unique variance accounted for by these factors,
      subjective intoxication was better predicted by simple motor speed, as indexed by
      performance on the Finger Tapping Test, than by executive control, as indexed by
      performance on the Trail Making Test. CONCLUSIONS: These results-generated from
      data collected in a naturally occurring setting-support previous findings from a
      more traditional laboratory-based investigation, thus illustrating the iterative
      process of linking field methodology and controlled laboratory experimentation.

PMID- 24117656
TI  - A randomized clinical trial of Cogmed Working Memory Training in school-age
      children with ADHD: a replication in a diverse sample using a control condition.
AB  - BACKGROUND: Cogmed Working Memory Training (CWMT) has received considerable
      attention as a promising intervention for the treatment of Attention
      Deficit/Hyperactivity Disorder (ADHD) in children. At the same time,
      methodological weaknesses in previous clinical trials call into question reported
      efficacy of CWMT. In particular, lack of equivalence in key aspects of CWMT
      (i.e., contingent reinforcement, time-on-task with computer training, parent
      child interactions, supportive coaching) between CWMT and placebo versions of
      CWMT used in previous trials may account for the beneficial outcomes favoring
      CWMT. METHODS: Eighty-five 7- to 11-year old school-age children with ADHD (66
      male; 78%) were randomized to either standard CWMT (CWMT Active) or a well
      controlled CWMT placebo condition (CWMT Placebo) and evaluated before and 3 weeks
      after treatment. Dependent measures included parent and teacher ratings of ADHD
      symptoms; objective measures of attention, activity level, and impulsivity; and
      psychometric indices of working memory and academic achievement (Clinical trial
      title: Combined cognitive remediation and behavioral intervention for the
      treatment of Attention-Deficit/Hyperactivity Disorder;
      http://clinicaltrials.gov/ct2/show/NCT01137318). RESULTS: CWMT Active
      participants demonstrated significantly greater improvements in verbal and
      nonverbal working memory storage, but evidenced no discernible gains in working
      memory storage plus processing/manipulation. In addition, no treatment group
      differences were observed for any other outcome measures. CONCLUSIONS: When a
      more rigorous comparison condition is utilized, CWMT demonstrates effects on
      certain aspects of working memory in children with ADHD; however, CWMT does not
      appear to foster treatment generalization to other domains of functioning. As
      such, CWMT should not be considered a viable treatment for children with ADHD.

PMID- 24117657
TI  - The impact of work culture on quality of care in nursing homes--a review study.
AB  - AIM: The main aim of this review study was to identify which factors that
      characterise the relationship between work culture and quality of care in nursing
      homes. METHOD: This review study was structured through systematic search methods
      to identify articles that describe the relationship between work culture and
      quality of care in nursing homes. The database search yielded 14510 hits. Closer
      examination showed that 10401 of these hits were duplicates. Of the remaining
      4109 articles, only 10 were related to our aim for the study. A qualitative
      method were used to explain and understand phenomena of work culture and quality
      if care in nursing homes. FINDINGS: Nine out of 10 articles in this review study
      emphasise the importance of leadership style and supportive management to
      increase quality of care in nursing homes. Increased empowerment, participation
      and influence were important factors for improving quality of care. Significant
      associations between work culture and quality of care and between empowerment and
      quality of care were reported. CONCLUSION: Nursing management and leaders must
      take in consideration that work culture is crucial for improving quality of care
      in nursing homes, and this study can be used to increase the focus on the work
      culture among healthcare personnel in nursing homes. Changes are necessary to
      increase healthcare personnel's job satisfaction, empowerment, autonomy and
      influence in nursing homes. Giving empowerment to the healthcare personnel
      working in nursing homes is both an organisational and an interpersonal issue.
      Being given empowerment and influence over their own work situation, the
      healthcare workers can be more committed and involved in the goal of obtaining
      best possible care to the residents.

PMID- 24117658
TI  - Aortic intima-media thickness measured by trans-abdominal ultrasound as an early
      life marker of subclinical atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory process that begins in early life.
      Improved identification of markers of early atherosclerosis via neonatal aortic
      intima-media thickness (aIMT) measurement may allow the development of
      interventions to prevent or reduce later cardiovascular disease. CONCLUSION:
      Using aIMT, studies have shown that antenatal factors such as intra-uterine
      growth retardation, prematurity, maternal factors and inflammation are associated
      with early cardiovascular changes.

PMID- 24117659
TI  - Detection of channel catfish virus in cage-cultured Pangasius hypophthalmus
      (Sauvage, 1878) in Malaysia.

PMID- 24117660
TI  - Quantitative standards for absolute linguistic universals.
AB  - Absolute linguistic universals are often justified by cross-linguistic analysis:
      If all observed languages exhibit a property, the property is taken to be a
      likely universal, perhaps specified in the cognitive or linguistic systems of
      language learners and users. In many cases, these patterns are then taken to
      motivate linguistic theory. Here, we show that cross-linguistic analysis will
      very rarely be able to statistically justify absolute, inviolable patterns in
      language. We formalize two statistical methods--frequentist and Bayesian--and
      show that in both it is possible to find strict linguistic universals, but that
      the numbers of independent languages necessary to do so is generally
      unachievable. This suggests that methods other than typological statistics are
      necessary to establish absolute properties of human language, and thus that many
      of the purported universals in linguistics have not received sufficient empirical
      justification.

PMID- 24117661
TI  - Expression and prognostic significance of fibronectin and matrix metalloproteases
      in breast cancer metastasis.
AB  - AIMS: Fibronectin (FN) has attracted interest in cancer research, owing to its
      role in tumour progression. The aims of this study were to investigate the
      expression and clinical relevance of FN in breast cancer, and to explore its
      relationship with the expression of matrix metalloproteases (MMPs) and their
      inhibitors (TIMPs). METHODS AND RESULTS: An immunohistochemical study was
      performed using tumours from 110 breast cancer patients, with tissue arrays and
      specific antibodies against FN, MMP-7, MMP-9, MMP-11, TIMP-1, and TIMP-2. The
      results indicated that FN expression was related to tumour size, histological
      grade, and MMP-9 expression. Tumours with high FN expression by tumour cells were
      significantly associated with a higher probability of metastasis, poorer overall
      survival, and expression of MMP-7, MMP-9, MMP-11, TIMP-1 and TIMP-2 by
      mononuclear inflammatory cells (MICs). In addition, the combination of FN
      expression by tumour cells and MMP-11 by MICs was strongly associated with
      distant metastasis development. CONCLUSIONS: Breast carcinomas with distant
      metastasis frequently have tumour cells expressing intracellular FN. There is a
      strong association between FN expression by tumour cells and MMP or TIMP
      expression by stromal MICs, and this may represent crosstalk that is of
      prognostic relevance in breast cancer.

PMID- 24117662
TI  - A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22
      gene (PTPN22) is associated with Type 1 diabetes in a Chinese population.
AB  - AIMS: To examine single nucleotide polymorphisms in the protein tyrosine
      phosphatase N22 gene (PTPN22) and to study their association with Type 1 diabetes
      in a Chinese cohort. METHODS: Three hundred and sixty-four young patients with
      Type 1 diabetes and 719 healthy children were included in this case-controlled
      study. The genotypes of rs1217385, rs2488457 (-1123C>G), rs1217414, rs1217419,
      rs3765598 and rs2476601 (1858C>T) in the PTPN22 gene were determined using the
      SNaPshot method. Alleles, genotypes and haplotype frequencies were compared
      between patients with Type 1 diabetes and healthy control subjects. The
      association between single nucleotide polymorphisms and clinical
      traits/autoantibody status was also analysed. RESULTS: The single nucleotide
      polymorphism, rs1217419, located in the second intron of the PTPN22 gene was
      associated with Type 1 diabetes (odds ratio 1.5, 95% CI 1.14-1.97, P = 0.003). An
      additional single nucleotide polymorphism, rs1217385, was also associated with
      Type 1 diabetes; however, the association was secondary to that of rs1217419. The
      previously reported single nucleotide polymorphism that is associated with Type 1
      diabetes (-1123G>C) had only marginal association with Type 1 diabetes in our
      study. A marginal association was also identified between -1123G>C and glutamic
      acid decarboxylase autoantibody positivity in patients with Type 1 diabetes.
      There was no association between the single nucleotide polymorphism 1858C>T and
      Type 1 diabetes in our studied cohort. CONCLUSIONS: Our study confirmed that
      PTPN22 is a gene that contributes to Type 1 diabetes susceptibility. The primary
      association occurs with single nucleotide polymorphism rs1217419 and there is
      clear heterogeneity of the association between PTPTN22 polymorphisms and Type 1
      diabetes in a Chinese population compared with other populations.

PMID- 24117663
TI  - The link between parental allergy and offspring allergic and nonallergic
      rhinitis.
AB  - BACKGROUND: Parental allergy-related disease increases the risk for rhinitis, but
      it remains unknown how different phenotypes of parental allergy affect this risk.
      The aim of this study was to investigate how parental hay fever, asthma, and
      eczema affect the risk of allergic rhinitis (AR) and nonallergic rhinitis (NAR)
      at 8 years of age. METHODS: Information on 2413 children from a population-based
      birth cohort was used combining questionnaire data and IgE to inhalant allergens.
      Logistic regression was used to estimate the association between parental allergy
      related disease and AR and NAR. In addition, cluster analysis was used to search
      for latent phenotypes of heredity likely to be associated with AR and NAR.
      RESULTS: At age 8 years, 13.8% of the children had AR, while 6.4% had NAR.
      Parental isolated hay fever increased the odds of AR (OR 2.2, 95% CI 1.6-3.2),
      whereas isolated asthma or eczema did not. The odds of NAR increased when one
      parent had two or more allergy-related diseases. In the cluster analysis, the
      highest proportion of AR, 37.5%, was seen in a cluster where both parents had hay
      fever and pollen allergy and that of NAR, 11.0%, in a cluster where one parent
      had hay fever, pollen allergy, and eczema. CONCLUSIONS: Parental allergy-related
      disease may be an important risk factor for NAR as well as AR, and the risk is
      comparable for maternal and paternal allergy. Parental hay fever seems to be the
      dominating hereditary risk factor for AR.

PMID- 24117664
TI  - Conscientious refusal and health professionals: does religion make a difference?
AB  - Freedom of Conscience and Freedom of Religion should be taken to protect two
      distinct sets of moral considerations. The former protects the ability of the
      agent to reflect critically upon the moral and political issues that arise in her
      society generally, and in her professional life more specifically. The latter
      protects the individual's ability to achieve secure membership in a set of
      practices and rituals that have as a moral function to inscribe her life in a
      temporally extended narrative. Once these grounds are distinguished, it becomes
      more difficult to grant healthcare professionals' claims to religious exemptions
      on the basis of the latter than it is on the basis of the former. While both sets
      of considerations generate 'internal reasons' for rights to accommodation, the
      relevant 'external' reasons present in the case of claims of moral conscience do
      not possess analogues in the case of claims of religious conscience. However, the
      argument applies only to 'irreducibly religious' claims, that is to claims that
      cannot be translated into moral vocabulary. What's more, there may be reasons to
      grant the claims of religious persons to exemptions that have to do not with the
      nature of the claims, but with the beneficial effects that the presence of
      religious persons may have in the context of the healthcare institutions of multi
      faith societies. 

PMID- 24117665
TI  - Fc gamma receptor IIa-H131R polymorphism and malaria susceptibility in sympatric
      ethnic groups, Fulani and Dogon of Mali.
AB  - It has been previously shown that there are some interethnic differences in
      susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani
      and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in
      the Fulani has not been fully explained by genetic polymorphisms previously known
      to be associated with malaria resistance, including haemoglobin S (HbS),
      haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase
      (G6PD) deficiency. Given the observed differences in the distribution of
      FcgammaRIIa allotypes among different ethnic groups and with malaria
      susceptibility that have been reported, we analysed the rs1801274-R131H
      polymorphism in the FcgammaRIIa gene in a study of Dogon and Fulani in Mali (n =
      939). We confirm that the Fulani have less parasite densities, less parasite
      prevalence, more spleen enlargement and higher levels of total IgG antibodies
      (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05)
      compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher
      frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P <
      0.001). With regard to the FcgammaRIIa polymorphism and allele frequency, the
      Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341,
      P < 0.0001), which was associated with greater total IgE production (P = 0.004).
      Our findings show that the FcgammaRIIa polymorphism might have an implication in
      the relative protection seen in the Fulani tribe, with confirmatory studies
      required in other malaria endemic settings.

PMID- 24117666
TI  - Efficacy of disulfiram for the treatment of alcohol dependence assessed with a
      multicenter randomized controlled trial.
AB  - BACKGROUND: The efficacy of disulfiram in preventing an alcoholic relapse has
      been controversial. The aim of our study was to assess the efficacy of supervised
      disulfiram for the treatment of alcohol dependence with a multi-institutional
      study in Japan. METHODS: In a single-blinded, randomized placebo-controlled
      study, we recruited 109 patients diagnosed with alcohol dependence under ICD-10
      criteria. The patients were randomly allocated to 4 treatment groups, depending
      on whether they took disulfiram (200 mg daily) or a placebo or whether they
      received adjunctive therapy consisting of mailed letters which delineated and
      emphasized the harmful effect of alcohol and the management of alcohol craving.
      The proportion of abstinence among the 4 groups at 26 weeks after discharge was
      the primary outcome measure. The proportion of abstinence was compared with the
      severity of alcohol dependence and craving. Furthermore, we examined the
      proportion of abstinence in patients with inactive aldehyde dehydrogenase-2
      (ALDH2). RESULTS: There were no significant differences among the 4 groups in
      terms of abstinent patients or study dropouts. The ratio of abstinence was not
      related to the severity of alcohol dependence or the degree of alcohol craving.
      Patients with inactive ALDH2 significantly sustained abstinence with the use of
      disulfiram (p = 0.044). CONCLUSIONS: Supervised oral disulfiram use followed by
      intervention via letters seems to be ineffective for increasing abstinence.
      Further studies are necessary to prove the efficacy of disulfiram for the
      pharmacological treatment of alcohol dependence. We indicated the effectiveness
      of disulfiram for the maintenance of abstinence in patients with inactive ALDH2.

PMID- 24117667
TI  - The importance of early screening and treatment of attention-deficit
      hyperactivity disorder in order to avoid morbid obesity in children.

PMID- 24117668
TI  - Affective neural response to restricted interests in autism spectrum disorders.
AB  - BACKGROUND: Restricted interests are a class of repetitive behavior in autism
      spectrum disorders (ASD) whose intensity and narrow focus often contribute to
      significant interference with daily functioning. While numerous neuroimaging
      studies have investigated executive circuits as putative neural substrates of
      repetitive behavior, recent work implicates affective neural circuits in
      restricted interests. We sought to explore the role of affective neural circuits
      and determine how restricted interests are distinguished from hobbies or
      interests in typical development. METHODS: We compared a group of children with
      ASD to a typically developing (TD) group of children with strong interests or
      hobbies, employing parent report, an operant behavioral task, and functional
      imaging with personalized stimuli based on individual interests. RESULTS: While
      performance on the operant task was similar between the two groups, parent report
      of intensity and interference of interests was significantly higher in the ASD
      group. Both the ASD and TD groups showed increased BOLD response in widespread
      affective neural regions to the pictures of their own interest. When viewing
      pictures of other children's interests, the TD group showed a similar pattern,
      whereas BOLD response in the ASD group was much more limited. Increased BOLD
      response in the insula and anterior cingulate cortex distinguished the ASD from
      the TD group, and parent report of the intensity and interference with daily life
      of the child's restricted interest predicted insula response. CONCLUSIONS: While
      affective neural network response and operant behavior are comparable in typical
      and restricted interests, the narrowness of focus that clinically distinguishes
      restricted interests in ASD is reflected in more interference in daily life and
      aberrantly enhanced insula and anterior cingulate response to individuals' own
      interests in the ASD group. These results further support the involvement of
      affective neural networks in repetitive behaviors in ASD.

PMID- 24117670
TI  - Diffuse lung disease in infancy and childhood: expanding the chILD
      classification.
AB  - AIMS: Diffuse parenchymal lung diseases (DPLD) in children comprise a wide
      spectrum of rare disorders. In 2007 the Children's Interstitial Lung Disease
      (chILD) Research Cooperative proposed a classification system for DPLD in
      children <2 years of age. The aims of our study were to determine the utility and
      reproducibility of this system in children <2 years of age, and test its
      extension to 18 years of age. METHODS AND RESULTS: Of 211 cases, 93 were <2 years
      of age at presentation and 58% were included in the chILD classification. In 118
      cases aged between 2 and 18 years there was a wider distribution of disorders,
      overlapping with those seen in adults, necessitating expansion of the chILD
      classification types to encompass all reviewed cases, in particular patients with
      'adult' diffuse lung diseases. Many cases showed mixed histological patterns,
      overlap often being between groups of disorders more prevalent in infancy.
      Concordance between reporting pathologists was 90%. CONCLUSIONS: The chILD scheme
      allows classification of conditions more common in children <2 years of age. It
      can be applied to children of any age, although additional entities need to be
      included. We propose a more histologically based system for use when assessing
      biopsies in this context.

PMID- 24117669
TI  - Leveraging paraprofessionals and family strengths to improve coverage and
      penetration of nutrition and early child development services.
AB  - Children need to be protected in intergenerational networks, with parents who
      have positive mood, resources to feed their children, and skills to promote early
      childhood development (ECD). Globally, more than 200 million children are raised
      annually without these resources. This article reviews the potential
      contributions of increasing coverage and penetration of services for these
      children, challenges to achieving penetration of services in high-risk families,
      opportunities created by bundling multiple services within one provider,
      potential leveraging of paraprofessionals to deliver care, and mobilizing
      communities to support children in households at high risk for negative outcomes.
      We end with a number of suggestions for how to ensure the equitable scale-up of
      integrated ECD and nutrition services that take into account current global
      priorities, as well as coverage and penetration of services. 

PMID- 24117671
TI  - The transcription of the neuD gene is stronger in serotype III group B
      streptococci strains isolated from cerebrospinal fluid than in strains isolated
      from vagina.
AB  - Group B streptococci (GBS) are a major cause of neonatal meningitis, and sialic
      acid is a determinant of the development of meningitis. The transcription level
      of the neuD gene, used as a marker of neu gene expression and capsular
      production, was significantly higher in serotype III GBS strains isolated from
      meningitis than from vaginal carriage. This was irrespective both of the
      phylogenetic position of strains and of the presence of a thymine at position 264
      in the neuD gene. Differences in neuD gene transcription may explain in part why
      particular isolates among the GBS strains colonizing the vagina can cause
      meningitis. 

PMID- 24117672
TI  - Effect of transient warming of red blood cells for up to 24 h: in vitro
      characteristics in CPD/saline-adenine-glucose-mannitol environment.
AB  - BACKGROUND AND OBJECTIVES: There are few studies on transient warming of red
      blood cells (RBCs). Occasional storage outside restricted temperature range often
      results in destroying of the RBC unit, even after a short period of time due to
      national guidelines. This study evaluates the in vitro effects associated with
      such accidental warming on RBCs stored in saline-adenine-glucose-mannitol (SAGM)
      and prepared within 8 h after blood collection. STUDY DESIGN AND METHODS: This
      study includes both repeated short-term exposure of RBCs to room temperature for
      6 h as wells as warming for either 6, 12, 18 or 24 h after 1 week or after 3
      weeks of storage in two separate studies. RBCs were stored for 42 days. We weekly
      measured pH, K(+) , glucose, lactate, haemolysis, red cell ATP and 2,3
      diphosphoglycerate. RESULTS: The lowest individual ATP value observed in any of
      the groups of warmed units was 2.6 MUmol/g haemoglobin. Increased haemolysis in
      warmed units was noted in two of the studies. None of the individual units
      exceeded the European maximum limit of 0.8% haemolysis. CONCLUSION: Our results
      suggest that quality of RBCs after transient warming will be maintained at
      acceptable levels specified in standards and in previous studies. However,
      increased haemolysis was observed when transient warming occurred during the
      second part of the storage period of 6 weeks suggesting that RBCs are more
      vulnerable to warming by the end of storage.

PMID- 24117673
TI  - Access to endodontic care in North Carolina public health and Medicaid settings.
AB  - OBJECTIVES: The purpose of this study was to investigate issues related to access
      to endodontic care in North Carolina for individuals who used dental public
      health resources such as public health clinics (PHCs) or private practices that
      accept Medicaid or other government-sponsored reimbursement programs private
      practices that accept Medicaid (PPM). METHODS: Surveys were sent to 1,195
      dentists regarding frequency and type of endodontic conditions encountered,
      treatments provided, and perceived barriers to care. Results were analyzed using
      logistic regression with the level of significance set at 0.05. RESULTS: Five
      hundred forty-six surveys were returned for a 45.7% response rate. Of the
      respondents, 79% reported frequently encountering an endodontic condition, but
      only 34% reported performing any type of definitive endodontic procedure.
      Graduates after the year 2000 were significantly more likely to perform
      definitive endodontic procedures (P < 0.05). Lack of insurance was the greatest
      barrier to care with 89% considering it a moderate to major barrier, followed by
      cost of the endodontic treatment (87%) and cost of the restoration following
      treatment (86%). PPMs were more likely to consider cost and insurance a major
      barrier (P < 0.05). CONCLUSIONS: In North Carolina public health and Medicaid
      settings, the frequency of endodontic treatments provided was much lower than the
      frequency of endodontic conditions encountered that might have benefited from
      treatment. Graduation year was the best indicator for the provision of root canal
      therapy. Additionally, treatment patterns and perceptions of barriers to care are
      different for PHCs and PPMs.

PMID- 24117674
TI  - Simultaneous extracorporeal membrane oxygenation and therapeutic plasma exchange
      procedures are tolerable in both pediatric and adult patients.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used in patients
      with pulmonary and/or cardiac disease. In rare circumstances, some patients may
      have to undergo simultaneous therapeutic plasma exchange (TPE). We sought to
      characterize simultaneous ECMO and TPE procedures at our institution. STUDY
      DESIGN AND METHODS: Retrospective analysis of medical records was performed for
      patients who underwent simultaneous ECMO and TPE. Patient demographics,
      diagnoses, TPE indications and variables, procedural complications, blood use,
      laboratory data, and outcomes were collected. RESULTS: Seventy-six patients
      underwent 293 simultaneous ECMO and TPE procedures; the majority involved
      pediatric patients, and most patients weighed less than 15 kg. In children, the
      two most frequent reasons for ECMO were congenital cardiac disease and sepsis; in
      adults, they were congestive heart failure or cardiomyopathy and severe pulmonary
      disease. In children, the two most frequent indications for TPE while on ECMO
      were multisystem organ failure and coagulopathy; in adults, they were humoral
      rejection of cardiac and pulmonary allografts. Blood product utilization during
      simultaneous ECMO and TPE was substantial in all patients. The complications of
      simultaneous ECMO and TPE were hypocalcemia (47 and 27.6% in children and adults,
      respectively) and hypotension (22.1 and 34.2% in children and adults,
      respectively). Approximately 45% of children and adults had resolutions of their
      apheresis indications after completing their TPE regimen. CONCLUSIONS: Despite
      the hypocalcemic and hypotensive reactions that occurred during simultaneous ECMO
      and TPE, apheresis treatment regimens were successfully completed in all
      patients. With clear communication between ECMO and apheresis teams, along with
      close patient and instrument monitoring, simultaneous ECMO and TPE is tolerable
      and can be performed in critically ill children and adults.

PMID- 24117675
TI  - Survival results after implantation of intrapericardial third-generation
      centrifugal assist device: an INTERMACS-matched comparison analysis.
AB  - Reports on third-generation centrifugal intrapericardial pumps (HeartWare
      International, Inc., Framingham, MA, USA) have shown better survival results than
      the previous-generation devices. However, outcomes depending on the preoperative
      level of stability can substantially differ, resulting in a limited analysis of
      potentialities and drawbacks of a given device. In the present study we sought to
      compare in our single-center experience the survival results of this third
      generation device with previous left ventricular systems taking into account the
      different preoperative Interagency Registry for Mechanically Assisted Circulatory
      Support (INTERMACS) levels. Between February 1993 and March 2012, 287 patients
      underwent assist device implantation in our university hospital (INTERMACS Level
      1-2 = 158 patients; INTERMACS Level 3-4-5 = 129 patients). Assist devices
      implanted were: Group A (HVAD HeartWare, n = 52), group B (previous continuous
      flow ventricular assist device [VAD], InCor [Berlin Heart, Berlin, Germany], n =
      37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey
      [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C
      (pulsatile systems, n = 159). After cumulative support duration of 54 436 days
      and a mean follow-up of 6.21 +/- 7.46 months (range 0-45.21 months), log-rank
      analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B
      of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24
      months respectively, with a significantly (P = 0.013) better outcome for group A.
      When stratifying the survival on the basis of INTERMACS level, no significant
      survival improvement was observed among all patients who underwent VAD
      implantation in INTERMACS 1-2 (P = 0.47). However, among patients who underwent
      elective VAD implantation (INTERMACS 3-4-5), group A had a significantly better
      outcome (P = 0.005) compared with the other INTERMACS-matched groups (B,C) with a
      survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at
      24 months, respectively. Elective HVAD system implantation shows improved
      survival benefit over the other INTERMACS-matched devices. Moreover, preoperative
      unstable hemodynamics resulted in a poor prognosis independently from the pump
      generation. 

PMID- 24117676
TI  - Tunnel technique with connective tissue graft versus coronally advanced flap with
      enamel matrix derivative for root coverage: a RCT using 3D digital measuring
      methods. Part I. Clinical and patient-centred outcomes.
AB  - AIM: The aim of this randomized clinical trial (RCT) was to introduce 3D digital
      measuring methods for evaluating the outcomes after surgical root coverage (RC)
      and to assess the clinical performance of the tunnel technique with subepithelial
      connective tissue graft (TUN) versus the coronally advanced flap (CAF) with
      enamel matrix derivative in the treatment of shallow localized gingival recession
      defects. MATERIAL AND METHODS: Twenty-four patients contributed a total of 47
      Miller class I or II recessions for scientific evaluation. Clinical outcomes were
      evaluated at 6 and 12 months. Precise study models gained at baseline and follow
      up examinations were optically scanned and virtually superimposed for digital
      evaluation of clinical outcome measures including percentage of RC and complete
      root coverage (CRC). Patient-centred outcomes were evaluated with questionnaires.
      Final aesthetic outcomes were assessed using the root coverage esthetic score
      (RES). RESULTS: At 12 months, RC was 98.4% for TUN-treated and 71.8% for CAF
      treated defects (p = 0.0004). CRC was observed in 78.6% (TUN) and 21.4% (CAF) of
      the cases (p = 0.0070). Results for patient-centred outcomes were equivalent for
      both groups but evaluation of the final aesthetic outcomes using the RES revealed
      a significant difference (9.06 versus 6.92, p = 0.0034) in favour of TUN.
      CONCLUSIONS: TUN resulted in significantly better clinical outcomes compared with
      CAF. The new measuring method provided high accuracy and unforeseen precision in
      the evaluation of treatment outcomes after surgical RC.

PMID- 24117677
TI  - Atopic dermatitis and the atopic march revisited.
AB  - Atopic dermatitis (AD) has become a significant public health problem because of
      increasing prevalence, together with increasing evidence that it may progress to
      other allergic phenotypes. While it is now acknowledged that AD commonly precedes
      other allergic diseases, a link termed 'the atopic march', debate continues as to
      whether this represents a causal relationship. An alternative hypothesis is that
      this association may be related to confounding by familial factors or phenotypes
      that comanifest, such as early-life wheeze and sensitization. However, there is
      increasing evidence from longitudinal studies suggesting that the association
      between AD and other allergies is independent of confounding by comanifest
      allergic phenotypes. The hypotheses on plausible biological mechanisms for the
      atopic march focus on defective skin barrier function and overexpression of
      inflammatory mediators released by the skin affected by AD (including thymic
      stromal lymphopoietin). Both human and animal studies have provided evidence
      supporting these potential biological mechanisms. Evidence from prevention trials
      is now critical to establishing a causal nature of the atopic march. An emerging
      area of research is investigation into environmental modifiers of the atopic
      march. Such information will assist in identifying secondary prevention
      strategies to arrest the atopic march. Despite much research into the aetiology
      of allergies, little progress has been made in identifying effective strategies
      to reduce the burden of allergic conditions. In this context, the atopic march
      remains a promising area of investigation. 

PMID- 24117678
TI  - Characterization of digital cameras for reflected ultraviolet photography;
      implications for qualitative and quantitative image analysis during forensic
      examination.
AB  - Reflected ultraviolet imaging techniques allow for the visualization of evidence
      normally outside the human visible spectrum. Specialized digital cameras
      possessing extended sensitivity can be used for recording reflected ultraviolet
      radiation. Currently, there is a lack of standardized methods for ultraviolet
      image recording and processing using digital cameras, potentially limiting the
      implementation and interpretation. A methodology is presented for processing
      ultraviolet images based on linear responses and the sensitivity of the
      respective color channels. The methodology is applied to a FujiS3 UVIR camera,
      and a modified Nikon D70s camera, to reconstruct their respective spectral
      sensitivity curves between 320 and 400 nm. This method results in images with low
      noise and high contrast, suitable for qualitative and/or quantitative analysis.
      The application of this methodology is demonstrated in the recording of latent
      fingerprints.

PMID- 24117679
TI  - Understanding the healthcare experiences of teenaged cancer patients and
      survivors.
AB  - BACKGROUND: Despite literature supporting a client and family-centred approach to
      healthcare delivery in paediatric facilities, there is little information about
      healthcare delivery from the perspective of teenagers in the oncology setting.
      The objective of this study is to describe the healthcare experiences of
      teenagers with cancer. METHODS: As part of a larger study on teen-centred care
      delivery in paediatric oncology, a survey included several open-ended questions
      to learn about the following: (1) what teenagers liked about the cancer care they
      received; (2) what they disliked about the cancer care received; and (3) what
      they would include if they could design the perfect cancer centre for teenagers.
      The survey was completed by 200 teenagers (aged 12-20 years) from three
      paediatric hospitals in Canada. Answers to these questions were coded and
      developed into themes and subthemes using a thematic analysis approach. RESULTS:
      The number of patients providing answers was 89% for question 1, 63% for question
      2 and 68.5% for question 3. Likes and dislikes were conceptualized in terms of
      four key themes as follows: (1) staff at the treatment centre; (2) the cancer
      care they received; (3) the treatment centre itself; and (4) social activities.
      The most common suggestions for the perfect cancer centre included having access
      to better entertainment, more social opportunities to interact with peers, and a
      more comfortable environment for themselves and their families. CONCLUSION:
      Understanding teenagers' experiences in the paediatric oncology setting provides
      information that could be used to shape the delivery of healthcare in a way that
      is tailored to their needs. Further research in this area is required in order to
      improve existing oncology care.

PMID- 24117680
TI  - Anti-calponin 1 antibodies highlight intracytoplasmic inclusions of infantile
      digital fibromatosis.

PMID- 24117681
TI  - Acute alcohol response phenotype in heavy social drinkers is robust and
      reproducible.
AB  - BACKGROUND: In 3 previously published works (Brumback et al., 2007, Drug Alcohol
      Depend 91:10-17; King et al., 2011a, Arch Gen Psychiatry 68:389-399; Roche and
      King, 2010, Psychopharmacology (Berl) 212:33-44), our group characterized acute
      alcohol responses in a large group of young, heavy binge drinkers (n = 104)
      across a variety of subjective, eye-tracking, and psychometric performance
      measures. METHODS: The primary goal of the current study was to directly
      replicate prior findings of alcohol response in heavy social drinkers (HD) in a
      second independent cohort (n = 104) using identical methodology. A secondary goal
      was to examine the effects of family history (FH) of alcohol use disorders (AUD)
      on acute alcohol response in both samples. Participants attended 2 randomized
      laboratory sessions in which they consumed 0.8 g/kg alcohol or a taste-masked
      placebo. At pre- and post-drink time points, participants completed subjective
      scales, psychomotor performance and eye-movement tasks, and provided salivary
      samples for cortisol determination. RESULTS: Results showed that the second
      cohort of heavy drinkers exhibited a nearly identical pattern of alcohol
      responses to the original cohort, including sensitivity to alcohol's stimulating
      and hedonically rewarding effects during the rising breath alcohol content (BrAC)
      limb, increases in sedation during the declining BrAC limb, a lack of cortisol
      response, and psychomotor and eye-tracking impairment that was most evident at
      peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol
      in the second cohort were similar to the first cohort across all measures, with
      the exception of 3 eye-movement measures: pro- and antisaccade accuracy and
      antisaccade velocity. FH of AUD did not affect alcohol response in the first
      cohort, and this was replicated in the second cohort. CONCLUSIONS: In sum, in 2
      independent samples, we have demonstrated that HD display a consistent and
      reliable sensitivity to alcohol's subjective effects and impairment of eye
      tracking and psychomotor performance, which is not affected by FH status. This
      acute alcohol response phenotype in heavy, frequent binge drinkers appears to be
      robust and reproducible.

PMID- 24117682
TI  - Standard of care, institutional obligations, and distributive justice.
AB  - The problem of standard of care in clinical research concerns the level of
      treatment that investigators must provide to subjects in clinical trials.
      Commentators often formulate answers to this problem by appealing to two distinct
      types of obligations: professional obligations and natural duties. In this
      article, I investigate whether investigators also possess institutional
      obligations that are directly relevant to the problem of standard of care, that
      is, those obligations a person has because she occupies a particular
      institutional role. I examine two types of institutional contexts: (1) public
      research agencies - agencies or departments of states that fund or conduct
      clinical research in the public interest; and (2) private-for-profit
      corporations. I argue that investigators who are employed or have their research
      sponsored by the former have a distinctive institutional obligation to conduct
      their research in a way that is consistent with the state's duty of distributive
      justice to provide its citizens with access to basic health care, and its duty to
      aid citizens of lower income countries. By contrast, I argue that investigators
      who are employed or have their research sponsored by private-for-profit
      corporations do not possess this obligation nor any other institutional
      obligation that is directly relevant to the ethics of RCTs. My account of the
      institutional obligations of investigators aims to contribute to the development
      of a reasonable, distributive justice-based account of standard of care. 

PMID- 24117683
TI  - Diabetes-oriented learning family intervention (DOLFIN): a feasibility study
      evaluating an intervention for carers of young persons with Type 1 diabetes.
AB  - AIMS: To describe the development of an intervention for parents and carers of
      young people with Type 1 diabetes and assess the feasibility, acceptability and
      emerging clinical themes. METHODS: Participants were carers of young persons aged
      10-18 years with a diagnosis of Type 1 diabetes of more than 12 months' duration
      in two inner-city South London hospitals. Carers were invited to attend six
      sessions of a group workshop where they received emotional support, diabetes
      education and were taught motivational interviewing techniques to support their
      child. RESULTS: Out of 106 eligible participants, carers of 31 young people with
      Type 1 diabetes were recruited, 17 of whom 'completed' the intervention
      (attending four or more sessions). Participants discussed a variety of themes in
      session, including the increasing difficulty of diabetes management as children
      grow older, parenting techniques for managing diabetes in the home and the
      emotional challenges of having a child with a chronic illness. CONCLUSIONS:
      Engaging parents in a carer intervention for Type 1 diabetes was a challenge, but
      parents who participated appeared to value the programme. Future interventions
      for carers need to take account of carers' wishes and expectations in order to
      maximize user uptake.

PMID- 24117684
TI  - Prevention and risk factors of hepatitis B recurrence after living donor liver
      transplantation.
AB  - BACKGROUND AND AIM: Without effective prophylaxis, liver transplantation (LT) for
      hepatitis B virus (HBV)-related liver disease is frequently complicated by severe
      and rapidly progressive HBV recurrence. The combination of low-dose hepatitis B
      immunoglobulin (HBIG) and the new nucleos(t)ide analog, entecavir, as prophylaxis
      for HBV recurrence after living-donor LT (LDLT) were analyzed. METHODS: A total
      of 315 patients with positive hepatitis B surface antigen underwent LDLT at our
      transplant center between July 2003 and December 2011. Our protocol for post
      transplantation HBV prophylaxis was a combination of low-dose HBIG and
      nucleos(t)ide analog. RESULTS: During a median follow-up period of 49 months post
      transplant, 10 patients (3.2%) had HBV recurrence, which was significantly
      related to hepatocellular carcinoma (HCC) at transplantation (P = 0.041) and post
      LT antiviral agent (P < 0.001) in multivariate analysis. The level of HBV DNA and
      hepatitis B e antigen state at transplantation were not significant factors for
      HBV recurrence (P = 0.342 and P = 0.802, respectively). In 170 patients with HCC
      at LDLT, HCC recurrence was significantly related to HBV recurrence (P < 0.001).
      Among 10 patients with HBV recurrence, three are alive and two had lost hepatitis
      B surface antigen. The remaining seven patients died of HCC recurrence.
      CONCLUSIONS: The combination of low-dose HBIG and nucleos(t)ide analogs is safe
      and effective for HBV prophylaxis after LDLT. As a post-LT antiviral treatment,
      entecavir is more effective than lamivudine. HCC at transplantation was
      significantly associated with HBV recurrence. HBV-related HCC patients who
      undergo LDLT require close virological monitoring.

PMID- 24117686
TI  - Timing of complementary feeding and the risk of atopic eczema.
AB  - AIM: To find out whether there was an association between when complementary
      feeding was introduced and the appearance of atopic eczema in children with a
      family history of allergy. METHODS: This prospective study followed 256 mother
      and child pairs until the child was four-years-old. Repeated skin prick testing
      was performed and a clinical diagnosis of eczema made by a physician. The mothers
      kept a continuous diary about the introduction of complementary feeding. To
      control the possible reverse causation of delaying complementary food
      introduction due to presumed child allergy, parental suspicions of allergic
      reactions were recorded. RESULTS: The introduction of cereals and fish after
      seven-months-of-age was associated with an increased risk of atopic eczema.
      However, when the parents' suspicions that their child might be exhibiting
      symptoms of allergic disease were taken into account, this effect was no longer
      significant. CONCLUSION: We found no evidence that the timing of the introduction
      of complementary feeding increased the risk of atopic eczema in a high-risk
      cohort, when parental suspicions were taken into account. Therefore, it seems
      that families with a history of allergy can safely comply with current feeding
      recommendations, although confirmation in further studies is warranted.

PMID- 24117685
TI  - Non-motor parkinsonian pathology in aging A53T alpha-synuclein mice is associated
      with progressive synucleinopathy and altered enzymatic function.
AB  - Aging, the main risk factor for Parkinson's disease (PD), is associated with
      increased alpha-synuclein levels in substantia nigra pars compacta (SNc). Excess
      alpha-synuclein spurs Lewy-like pathology and dysregulates the activity of
      protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins,
      including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A
      loss of nigral dopaminergic neurons induces PD movement problems, but before
      those abnormalities occur, behaviors such as olfactory loss, anxiety, and
      constipation often manifest. Identifying mouse models with early PD behavioral
      changes could provide a model in which to test emerging therapeutic compounds. To
      this end, we evaluated mice expressing A53T mutant human (A53T) alpha-synuclein
      for behavior and alpha-synuclein pathology in olfactory bulb, adrenal gland, and
      gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled
      olfactory and adrenal alpha-synuclein aggregation. PP2A activity was also
      diminished in olfactory and adrenal tissues harboring insoluble alpha-synuclein.
      Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the
      first study to link adrenal synucleinopathy to anxiety and catecholamine
      dysregulation. Aggregated A53T alpha-synuclein recombinant protein also had
      impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data
      identify an excellent model in which to screen compounds for their ability to
      block the spread of alpha-synuclein pathology associated with pre-motor stages of
      PD.

PMID- 24117687
TI  - Prognostic significance of immunohistochemistry-based markers and algorithms in
      immunochemotherapy-treated diffuse large B cell lymphoma patients.
AB  - AIMS: To reassess the prognostic validity of immunohistochemical markers and
      algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large
      B cell lymphoma patients. METHODS AND RESULTS: The prognostic significance of
      immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1,
      LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally)
      was assessed using clinical diagnostic blocks taken from an unselected,
      population-based cohort of 190 patients treated with R-CHOP. Dichotomizing
      expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (>=80%) predicted
      shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively).
      High Bcl-2 (>=80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%)
      predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045
      and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS
      (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P =
      0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009
      and P = 0.023). In multivariate analysis, the International Prognostic Index
      (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and
      PFS; HR: 2.91, P < 0.001). CONCLUSIONS: Results highlight the controversy
      surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for
      more robust markers, applicable to the clinic, for incorporation into improved
      prognostic systems is emphasized.

PMID- 24117688
TI  - Nurses' encounters with children in child and school health care: negotiated
      guidance within a given frame.
AB  - BACKGROUND: Throughout childhood, children take part in health visits according
      to a health-monitoring programme. The visits are aimed to promote the children's
      development and health and to strengthen them to take own responsibility for
      their health. Nurses' actions when encountering children at these visits are not
      explored to any great extent. Exploring nurses' actions can facilitate their
      reflections on their actions towards children and thereby promote children's
      involvement in such visits. AIM: The aim of this study was to explore nurses'
      actions when encountering children at health visits. METHOD: A qualitative
      explorative design, based on 30 video recordings of health visits in child and
      school health care, was used in this study. These visits were ordinary real-life
      health visits. The data were subjected to qualitative content analysis. The right
      to conduct video recordings during health visits was approved by appropriate
      research ethics committees. RESULTS: The findings show that nurses, in order to
      carry out the health visits, encounter children through negotiated guidance. This
      guidance is understood as the process through which the nurses reach agreement
      with the children, and is comprised of directed and pliable strategies. At one
      moment, the nurse can use a directed strategy to inform the child and at the next
      moment a pliable strategy to provide the child space within the given frame, the
      health-monitoring programme. By using these strategies intertwined, the nurse can
      provide the child space within the given frame and, at the same time, fulfil
      his/her responsibility to promote children's health and development. CONCLUSION:
      The results highlight nurses' challenging and complex assignment of guiding
      children to promote their engagement in the health visits, thereby enabling the
      nurses to promote the children's health and development according to the national
      health-monitoring programme.

PMID- 24117689
TI  - Increased use of lethal methods and annual increase of suicide rates in Korean
      adolescents: comparison with adolescents in the United States.
AB  - BACKGROUND: The lethality of the suicide method is a strong risk factor for
      completed suicide. We examined whether the annual change in the pattern of
      suicide methods was related to the annual change in suicide rates among
      adolescents in South Korea and the United States. METHODS: We analyzed annual
      data for the 2000-2009 period for South Korea and the 2000-2008 period for the
      United States to examine time trends in the suicide rates and suicide methods of
      adolescents aged 10-19 years in two countries. Data on suicide methods were
      obtained from the World Health Organization (WHO) mortality database. RESULTS:
      Suicide rates among adolescents in the United States have remained relatively
      steady since 2000, whereas the suicide among Korean adolescents has increased.
      Between 2000 and 2009, the most common suicide method among Korean adolescents
      was jumping for boys and girls, whereas it was hanging for girls and firearms for
      boys in the United States. Along with the annual increase in suicide rates in
      South Korea, the incidences of jumping among males and hanging (and recently
      jumping) among females have increased steadily, whereas suicide by self-poisoning
      steadily decreased. In the United States, between 2000 and 2008, the proportion
      of suicides committed by hanging increased, whereas those committed using
      firearms steadily decreased, particularly among adolescent females. CONCLUSIONS:
      These findings suggest that the increased use of lethal suicide methods is
      reflected in the increase in suicide rates in Korean adolescents. The most
      fruitful approach to addressing the rises in jumping suicides among Korean
      adolescents and hanging suicides among adolescents in the United States may be
      through population-based initiatives to reduce the physical availability (e.g.,
      limiting access to or fencing off tall structures) and the social acceptability
      (e.g., effective and responsible regulations for reporting suicide) of these
      methods.

PMID- 24117690
TI  - Clinical cardiomyopathy syndrome in Atlantic salmon, Salmo salar L.

PMID- 24117691
TI  - Involvement of the anucleate primary sterigmata protein FgApsB in vegetative
      differentiation, asexual development, nuclear migration, and virulence in
      Fusarium graminearum.
AB  - The protein ApsB has been shown to play critical roles in the migration and
      positioning of nuclei and in the development of conidiophores in Aspergillus
      nidulans. The functions of ApsB in Fusarium graminearum, a causal agent of
      Fusarium head blight in China, are largely unknown. In this study, we used the
      blastp program at the Broad Institute to identify FgApsB, an F. graminearum
      homolog of A. nidulansApsB. The functions of FgApsB were evaluated by
      constructing a deletion mutant of FgApsB, designated DeltaFgApsB-28. Conidiation
      and mycelial growth rate are reduced in DeltaFgApsB-28. The hyphae of DeltaFgApsB
      28 are thinner than those of the wild type and have a different branching angle.
      DeltaFgApsB-28 exhibited reduced aerial hyphae formation, but increased
      production of rubrofusarin. Whereas nuclei are evenly distributed in germ tubes
      and hyphae of the wild type, they are clustered and irregularly distributed in
      DeltaFgApsB-28. The mutant exhibited increased resistance to cell wall-damaging
      agents, but reduced virulence on flowering wheat heads, which is consistent with
      its reduced production of the toxin deoxynivalenol. All of the defects in
      DeltaFgApsB-28 were restored by genetic complementation with the parental FgApsB
      gene. Taken together, the results indicate that FgApsB is important for
      vegetative differentiation, asexual development, nuclear migration, and virulence
      in F. graminearum. 

PMID- 24117693
TI  - Optimizing accu time-of-flight/direct analysis in real time for explosive residue
      analysis.
AB  - The use of a direct analysis in real time (DART) mass spectrometer (MS)
      instrument was optimized for 22 compounds of organic explosive residues to
      provide a guide for DART-MS users in rapid screening of explosive compounds.
      Samples were introduced as neat solutions and sequential dilutions to determine
      optimal instrument conditions and lowest concentration detectable. Most compounds
      were optimized to 250 degrees C in the negative ion mode, and several compounds
      benefited from the addition of a chloride dopant from methylene chloride (amino
      dinitrotoluenes, RDX, EGDN, and PETN). Few compounds were more sensitive in the
      positive ion mode (TEGDN, DEGDN, HNS, and DMNB). Mixtures of compounds were
      detected using clean room wipes, directly from their surfaces and from subsequent
      extractions. Compounds from the mixtures were also successfully detected in soil
      and from swipes of spiked surfaces. The instrument showed merit in detection of
      pg/MUL solutions for most of the compounds and among the substrates tested.

PMID- 24117692
TI  - Randomised controlled trial: sequential vs. standard triple therapy for
      Helicobacter pylori infection in Chinese children-a multicentre, open-labelled
      study.
AB  - BACKGROUND: Studies have showed that 10-day sequential treatment regimen achieved
      higher Helicobacter pylori eradication rate than standard triple therapies. AIM:
      To compare a 10-day sequential therapy and standard triple therapy in Chinese
      children with H. pylori infection. METHODS: A prospective, multicentre, open
      label, randomised controlled trial was conducted in four tertiary medical centres
      in China. Children with H. pylori gastritis were randomly assigned to a 10-day
      sequential therapy consisting of omeprazole and amoxicillin for 5 days followed
      by omeprazole, clarithromycin and metronidazole for the remaining 5 days, or 7
      day or 10-day standard triple therapy comprising of omeprazole, amoxicillin and
      clarithromycin. H. pylori eradication was assessed by H. pylori stool antigen
      test. RESULTS: A total of 360 patients were included. The eradication rate
      achieved with the 10-day sequential therapy was significantly higher than either
      the 7-day or 10-day standard triple treatment, either by the intention-to-treat
      analysis (81.4% vs. 61.9% or 67.7%, P < 0.05) or per-protocol analysis (89.7% vs.
      70.8% or 77.8%, P < 0.05). CONCLUSIONS: The 10-day sequential regimen was
      significantly more effective than standard 7-day or 10-day triple regimens in
      eradicating H. pylori infection in Chinese children.

PMID- 24117694
TI  - Determination of the influence of factors (ethanol, pH and a(w) ) on the
      preservation of cosmetics using experimental design.
AB  - OBJECTIVE: Ethanol, pH and water activity are three well-known parameters that
      can influence the preservation of cosmetic products. With the new constraints
      regarding the antimicrobial effectiveness and the restrictive use of
      preservatives, a D-optimal design was set up to evaluate the influence of these
      three parameters on the microbiological conservation. METHODS: To monitor the
      effectiveness of the different combination of these set parameters, a challenge
      test in compliance with the International standard ISO 11930: 2012 was
      implemented. The formulations established in our study could support wide
      variations of ethanol concentration, pH values and glycerin concentration without
      noticeable effects on the stability of the products. RESULTS: In the conditions
      of the study, determining the value of a single parameter, with the tested
      concentration, could not guarantee microbiological conservation. However, a high
      concentration of ethanol associated with an extreme pH could inhibit bacteria
      growth from the first day (D0). Besides, it appears that despite an aw above 0.6
      (even 0.8) and without any preservatives incorporated in formulas, it was
      possible to guarantee the microbiological stability of the cosmetic product when
      maintaining the right combination of the selected parameters. CONCLUSION:
      Following the analysis of the different values obtained during the
      experimentation, there seems to be a correlation between the aw and the selected
      parameters aforementioned. An application of this relationship could be to define
      the aw of cosmetic products by using the formula, thus avoiding the evaluation of
      this parameter with a measuring device.

PMID- 24117695
TI  - Infants with severe respiratory syncytial virus needed less ventilator time with
      nasal continuous airways pressure then invasive mechanical ventilation.
AB  - AIM: Nasal continuous positive airway pressure (NCPAP) has been proposed as an
      early first-line support for infants with severe respiratory syncytial virus
      (RSV) infection. We hypothesised that infants <6 months with severe RSV would
      require shorter ventilator support on NCPAP than invasive mechanical ventilation
      (IMV). METHODS: Retrospective cohort analysis of infants admitted to two
      paediatric intensive care units, one primarily using NCPAP and one exclusively
      using IMV, between January 2008 and February 2010. RESULTS: We studied 133 (NCPAP
      n = 89, IMV n = 46) consecutively admitted infants. On admission, disease
      severity [i.e. Paediatric RISk of Mortality (PRISM) II score (NCPAP 5.1 +/- 2.8
      vs. IMV 12.2 +/- 6.0, p < 0.001) and SpO2 /Fi O2 ratio (NCPAP 309 +/- 81 vs. IMV
      135 +/- 98, p < 0.001)] was higher in the IMV group. NCPAP remained independently
      associated with shorter ventilatory support (hazard ratio 2.3, 95% CI 1.1-4.7, p
      = 0.022) after adjusting for PRISM II score, PCO2 , SpO2 /Fi O2 ratio,
      bronchopulmonary dysplasia and occurrence of clinically suspected secondary
      bacterial pneumonia. CONCLUSION: Nasal continuous positive airway pressure was
      independently associated with a shorter duration of ventilatory support.
      Differences in baseline disease severity mandate a randomised trial before the
      routine use of NCPAP can be recommended.

PMID- 24117696
TI  - The Dentine Hypersensitivity Experience Questionnaire: a longitudinal validation
      study.
AB  - AIM: To validate the Dentine Hypersensitivity Experience Questionnaire in terms
      of responsiveness to change and to determine the minimally important difference.
      MATERIALS AND METHODS: The study was a secondary analysis of data from three
      randomized controlled trials with 311 participants. Three aspects of
      responsiveness were examined: change within individuals, differences among people
      who improved, stayed the same or worsened using an external referent and change
      due to treatment. Responsiveness to treatments of differing efficacy was assessed
      in trials with negative and active controls. RESULTS: The measure showed
      excellent internal reliability, test-retest reliability and criterion validity.
      The measure was highly responsive to change within individuals (Cohen's effect
      sizes: 0.28, 0.56, 0.86) showing decreases in the total score (i.e. improvement
      in OHrQoL) across all trials. The effect sizes in participants whose self
      reported QoL "improved" were large (0.73-1.31). Dentine Hypersensitivity
      Experience Questionnaire detected a treatment effect in one of two negative
      control trials (effect size: 0.47). Dentine Hypersensitivity Experience
      Questionnaire scores were similar in the test and control groups in the active
      control trial. The minimally important difference range was between 22 and 39
      points. CONCLUSIONS: The measure is longitudinally reliable, valid and responsive
      and can discriminate between treatments of different efficacy.

PMID- 24117697
TI  - Defining and measuring blood donor altruism: a theoretical approach from biology,
      economics and psychology.
AB  - BACKGROUND AND OBJECTIVES: While blood donation is traditionally described as a
      behaviour motivated by pure altruism, the assessment of altruism in the blood
      donation literature has not been theoretically informed. Drawing on theories of
      altruism from psychology, economics and evolutionary biology, it is argued that a
      theoretically derived psychometric assessment of altruism is needed. Such a
      measure is developed in this study that can be used to help inform both our
      understanding of the altruistic motives of blood donors and recruitment
      intervention strategies. MATERIALS AND METHODS: A cross-sectional survey (N =
      414), with a 1-month behavioural follow-up (time 2, N = 77), was designed to
      assess theoretically derived constructs from psychological, economic and
      evolutionary biological theories of altruism. Theory of planned behaviour (TPB)
      variables and co-operation were also assessed at time 1 and a measure of
      behavioural co-operation at time 2. RESULTS: Five theoretical dimensions (impure
      altruism, kinship, self-regarding motives, reluctant altruism and egalitarian
      warm glow) of altruism were identified through factor analyses. These five
      altruistic motives differentiated blood donors from non-donors (donors scored
      higher on impure altruism and reluctant altruism), showed incremental validity
      over TPB constructs to predict donor intention and predicted future co-operative
      behaviour. CONCLUSIONS: These findings show that altruism in the context of blood
      donation is multifaceted and complex and, does not reflect pure altruism. This
      has implication for recruitment campaigns that focus solely on pure altruism.

PMID- 24117698
TI  - Retrieval dynamics and retention in cross-situational statistical word learning.
AB  - Previous research on cross-situational word learning has demonstrated that
      learners are able to reduce ambiguity in mapping words to referents by tracking
      co-occurrence probabilities across learning events. In the current experiments,
      we examined whether learners are able to retain mappings over time. The results
      revealed that learners are able to retain mappings for up to 1 week later.
      However, there were interactions between the amount of retention and the
      different learning conditions. Interestingly, the strongest retention was
      associated with a learning condition that engendered retrieval dynamics that
      initially challenged the learner but eventually led to more successful retrieval
      toward the end of learning. The ease/difficulty of retrieval is a critical
      process underlying cross-situational word learning and is a powerful example of
      how learning dynamics affect long-term learning outcomes.

PMID- 24117699
TI  - Mapping modalities of self-awareness in mindfulness practice: a potential
      mechanism for clarifying habits of mind.
AB  - To better understand the neurobiological mechanisms by which mindfulness-based
      practices function in a psychotherapeutic context, this article details the
      definition, techniques, and purposes ascribed to mindfulness training as
      described by its Buddhist tradition of origin and by contemporary neurocognitive
      models. Included is theory of how maladaptive mental processes become habitual
      and automatic, both from the Buddhist and Western psychological perspective.
      Specific noting and labeling techniques in open monitoring meditation, described
      in the Theravada and Western contemporary traditions, are highlighted as
      providing unique access to multiple modalities of awareness. Potential explicit
      and implicit mechanisms are discussed by which such techniques can contribute to
      transforming maladaptive habits of mind and perceptual and cognitive biases,
      improving efficiency, facilitating integration, and providing the flexibility to
      switch between systems of self-processing. Finally, a model is provided to
      describe the timing by which noting and labeling practices have the potential to
      influence different stages of low- and high-level neural processing. Hypotheses
      are proposed concerning both levels of processing in relation to the extent of
      practice. Implications for the nature of subjective experience and self
      processing as it relates to one's habits of mind, behavior, and relation to the
      external world, are also described. 

PMID- 24117700
TI  - Does a decade of elevated [CO2] affect a desert perennial plant community?
AB  - Understanding the effects of elevated [CO2 ] on plant community structure is
      crucial to predicting ecosystem responses to global change. Early predictions
      suggested that productivity in deserts would increase via enhanced water-use
      efficiency under elevated [CO2], but the response of intact arid plant
      communities to elevated [CO2 ] is largely unknown. We measured changes in
      perennial plant community characteristics (cover, species richness and diversity)
      after 10 yr of elevated [CO2] exposure in an intact Mojave Desert community at
      the Nevada Desert Free-Air CO2 Enrichment (FACE) Facility. Contrary to
      expectations, total cover, species richness, and diversity were not affected by
      elevated [CO2]. Over the course of the experiment, elevated [CO2] had no effect
      on changes in cover of the evergreen C3 shrub, Larrea tridentata; alleviated
      decreases in cover of the C4 bunchgrass, Pleuraphis rigida; and slightly reduced
      the cover of C3 drought-deciduous shrubs. Thus, we generally found no effect of
      elevated [CO2] on plant communities in this arid ecosystem. Extended drought,
      slow plant growth rates, and highly episodic germination and recruitment of new
      individuals explain the lack of strong perennial plant community shifts after a
      decade of elevated [CO2].

PMID- 24117701
TI  - Extracorporeal life support after cardiac surgery in children: outcomes from a
      single institution.
AB  - Extracorporeal life support (ECLS) is used after congenital heart surgery for
      several indications, including failure to separate from cardiopulmonary bypass,
      postoperative low cardiac output syndrome, and extracorporeal cardiopulmonary
      resuscitation. Here, we assessed the outcomes of ECLS in children after cardiac
      surgery at our institution. Medical records of all children who required
      postoperative ECLS at our institution were reviewed. Between 2003 and 2011, 36
      (1.4%) of 2541 pediatric cardiac surgical cases required postoperative ECLS.
      Median age of patients was 64 days (range: 0 days-4.1 years). ECLS was in the
      form of either extracorporeal membrane oxygenation (ECMO; n = 24) or ventricular
      assist system (VAS; n = 12). Mean duration of ECLS was 4.9 +/- 4.2 days. Overall,
      21 patients (58%) were weaned off ECLS, and 17 patients (47%) were successfully
      discharged from the hospital. Patients with biventricular heart (BVH) had higher
      survival-to-hospital discharge rates compared with those with univentricular
      heart (UVH) (P = 0.019). Regarding ECLS type, UVH patients who received VAS
      showed higher rates of device discontinuation than UVH patients who received ECMO
      (P = 0.012). However, rates of hospital discharge were not significantly
      different between UVH patients who received VAS or ECMO. Surgical interventions,
      such as banding of Blalock-Taussig shunt to reduce pulmonary blood flow or
      placing bidirectional cavopulmonary shunt to minimize ventricular volume
      overload, were effective for weaning off ECLS in patients with UVH. ECLS is
      beneficial to children with low cardiac output after cardiac surgery. Rates of
      survival-to-hospital discharge were higher in BVH patients than UVH patients.
      Additional interventions to reduce ventricular volume load may be effective for
      discontinuing ECLS in patients with UVH. 

PMID- 24117702
TI  - Observational etiologic research. Part 4--Matching in case-control studies:
      almost always a bad idea.

PMID- 24117703
TI  - Aspirin 300 mg/day is effective for treating aspirin-exacerbated respiratory
      disease.
AB  - BACKGROUND: Aspirin desensitization (AD) treatment at doses of up to 1300 mg/day
      improves outcomes in aspirin-exacerbated respiratory disease (AERD). The aim of
      this study was to investigate the efficacy of aspirin 300 mg/day in the treatment
      of patients with AERD. METHODS: The study included 40 patients diagnosed in our
      clinic as AERD that were desensitized and treated with aspirin 300 mg/day between
      December 2005 and December 2012. Changes from the baseline status were analyzed
      at 1 year and at 3 years of follow-up. RESULTS: Of the 40 patients included, 24
      (60%) were female and median (interquartile range [IQR]) age was 45 (40-51)
      years. Median (IQR) duration of AD was 31.5 (10.5-48.5) months. In total, 29
      patients continued treatment for at least 1 year and 18 patients for at least 3
      years. The annual rate of use of systemic corticosteroid regimens, episodes of
      sinusitis, and surgery was significantly lower both at 1 year (P = 0.002, P =
      0.01, and P < 0.001, respectively) and at 3 years (P = 0.001, P = 0.03, and P =
      0.002, respectively). Significant improvement was observed in the nasal
      congestion score (P = 0.01) and sense of smell score (P = 0.05) at 1 year and in
      the postnasal drainage score (P = 0.01) at 3 years. CONCLUSION: Daily treatment
      with aspirin 300 mg had beneficial effects in patients with AERD, especially for
      the control of upper airway disease.

PMID- 24117704
TI  - Family environment and attention-deficit/hyperactivity disorder in adopted
      children: associations with family cohesion and adaptability.
AB  - BACKGROUND: Positive family environments are crucial in promoting children's
      emotional and behavioural well-being, and may also buffer development of
      attention-deficit/hyperactivity disorder (ADHD). ADHD is highly heritable, but
      psychosocial factors in the family environment, particularly family cohesion and
      communication, may mediate genetic predispositions. The purpose of the current
      study is to examine the mediating influence of the adoptive family environment
      between pre-adoptive risk factors and youths' ADHD symptomatology at 14 years
      post adoption. METHODS: The data used in this study were obtained from the fourth
      wave of the California Long-Range Adoption Study (CLAS) (n = 449). Using
      structural equation modelling (SEM), family sense of coherence and family
      adaptability were tested as possible mediators between environmental and
      biological predictors and ADHD symptomatology. Predictors included birthweight,
      gender, age at adoption, adoption from foster care, transracial adoption status,
      ethnicity and having a previous diagnosis of ADHD. RESULTS: Results show that,
      while adoption from foster care is negatively associated with family functioning,
      higher family cohesion and adaptability mediate this influence on children's ADHD
      symptomatology. Older age of adoption directly predicts greater ADHD symptoms
      with no mediating influence of the family environment. CONCLUSIONS: The mediating
      influence of the family environment between children's risk factors and ADHD
      symptoms suggests that family intervention strategies may be helpful in improving
      adopted children's outcomes. Once children are adopted, targeting family
      communication patterns and dynamics may be an additional part of developing an
      evidence-based, post-adoption services toolkit.

PMID- 24117705
TI  - Gastrointestinal stromal tumours: from KIT to succinate dehydrogenase.
AB  - The discovery of activating mutations in the tyrosine kinase receptor genes KIT
      and PDGFRA has led to the development of effective targeted therapies for
      gastrointestinal stromal tumours (GISTs). Specific genotypes, in part, predict
      the response to treatment with tyrosine kinase inhibitors. However, ~10% of GISTs
      lack such mutations (often referred to as 'wild-type' GISTs). Recent insights
      into the biology of 'wild-type' GISTs have resulted in clinically significant
      subclassification of this heterogeneous group of tumours, a large subset of which
      are now known to represent succinate dehydrogenase-deficient GISTs. Recognition
      of this distinctive class of tumours has critical implications for prognosis,
      therapy, clinical follow-up, and genetic counselling. Other uncommon genetic
      groups include neurofibromatosis type I-associated and BRAF-mutant GISTs. This
      review provides an update on the diagnosis and pathogenesis of these less common
      classes of GISTs, summarizes the clinical and pathological features associated
      with particular genotypes, and discusses mechanisms of resistance to targeted
      therapies. 

PMID- 24117707
TI  - Social patterning in knowledge following an informed choice invitation for type 2
      diabetes screening.
AB  - AIMS: To describe prevalence of knowledge of items specified by the U.K. General
      Medical Council as required to make an informed choice following an invitation
      for screening for type 2 diabetes and investigate whether knowledge was socio
      economically patterned. METHODS: A 9-item knowledge questionnaire was employed
      immediately following an informed choice invitation to type 2 diabetes screening
      that was piloted with 278 people between 40 and 69 years in the U.K. between
      February and April 2006. RESULTS: With the exception of post-diagnosis treatment
      and the effectiveness of early treatment in preventing long-term problems,
      information was typically understood correctly. Social patterning was observed:
      individuals who left full-time education before 19 years of age were less likely
      to understand the most likely test result, the effectiveness of early treatment
      in preventing long-term problems or the possible harms of screening. CONCLUSIONS:
      Even risk communication materials developed for ease of readability can result in
      inequity, limiting autonomy in healthcare decisions.

PMID- 24117708
TI  - Biomedical enhancements as justice.
AB  - Biomedical enhancements, the applications of medical technology to make better
      those who are neither ill nor deficient, have made great strides in the past few
      decades. Using Amartya Sen's capability approach as my framework, I argue in this
      article that far from being simply permissible, we have a prima facie moral
      obligation to use these new developments for the end goal of promoting social
      justice. In terms of both range and magnitude, the use of biomedical enhancements
      will mark a radical advance in how we compensate the most disadvantaged members
      of society. 

PMID- 24117706
TI  - Frequency-dependent effects of ethanol on dopamine release in the nucleus
      accumbens.
AB  - BACKGROUND: Ethanol (EtOH) is known to have excitatory effects on dopamine (DA)
      release, with moderate-to-high doses (0.5 to 2.5 g/kg) of acute EtOH enhancing DA
      neuron firing rates in the ventral tegmental area (VTA) and DA levels in the
      nucleus accumbens (NAc). EtOH has also been shown to reduce DA activity, with
      moderate doses (1 to 2 g/kg) attenuating electrically evoked release, and higher
      doses (5 g/kg) decreasing NAc DA levels, demonstrating a biphasic effect of EtOH
      on DA release. The purpose of the current study was to evaluate EtOH's inhibitory
      effects on NAc DA terminal release under low- and high-frequency stimulation
      conditions. METHODS: Using fast-scan cyclic voltammetry in NAc slices from
      C57BL/6J mice, we examined EtOH's (40 to 160 mM) effects on DA release under
      several different stimulation parameters, varying frequency (5 to 125 Hz), number
      of pulses (1 to 10), and stimulation intensity (50 to 350 MUA). Additionally,
      calcium concentrations were manipulated under high-frequency stimulation
      conditions (20 Hz, 10 pulses, 350 MUA) to determine whether EtOH's effects were
      dependent upon calcium concentration, and by extension, the amount of DA release.
      RESULTS: Acute EtOH (40 to 160 mM) inhibited DA release to a greater extent under
      high-frequency, multiple-pulse stimulation conditions, with increased sensitivity
      at 5 and 10 pulses and frequencies of 20 Hz or higher. High-frequency, multiple
      pulse stimulations also resulted in greater DA release compared with single-pulse
      release, which was controlled by reducing stimulation intensity. Under reduced DA
      conditions, high-frequency stimulations still showed increased EtOH sensitivity.
      Reducing calcium levels also decreased DA release at high-frequency stimulations,
      but did not affect EtOH sensitivity. CONCLUSIONS: EtOH appears to inhibit DA
      release at NAc terminals under high-frequency stimulation conditions that are
      similar to release events observed during phasic burst firing in DAergic neurons,
      suggesting that EtOH may provide inhibition of DA terminals selectively during
      phasic signaling, while leaving tonic DA terminal activity unaffected.

PMID- 24117709
TI  - Sucrose for procedural pain control in infants: should we change our practice?

PMID- 24117711
TI  - Patient participation in pressure injury prevention: giving patient's a voice.
AB  - Pressure injuries burden patients and healthcare organisations, with some
      preventative practices having little impact on prevalence reduction. Patient
      participation in care may be an effective pressure injury prevention strategy,
      yet patient preferences are unknown. The aim of this interpretive study was to
      describe patients' perceptions of their current and future role in pressure
      injury prevention. Semi-structured interviews were conducted with 20 adult
      inpatients recruited from four medical units, at two Australian metropolitan
      hospitals. Interview data were analysed using content analysis, with three
      categories emerging: 'experiencing pressure injuries'; 'participating in pressure
      injury prevention'; and 'resourcing pressure injury prevention and treatment'.
      These categories reflect the complex nature of participants' pressure injury
      experience. The findings suggest participants gather pressure injury knowledge
      from first-hand and vicarious experience; knowledge they bring to hospital. Most
      participants preferred a proactive pressure injury prevention role. Many
      identified barriers in the healthcare environment that impeded their
      participation and affected their experience of pressure injuries and pressure
      injury prevention. If patient participation as a pressure injury prevention
      strategy is to be considered, nurses and organisations need to view patients as
      partners. 

PMID- 24117710
TI  - Sociodemographic disparities and behavioral factors in clinical oral health
      status during pregnancy.
AB  - OBJECTIVES: Although oral health (OH) problems are common during pregnancy,
      little is known about individual characteristics or behaviors relating to
      clinically assessed OH during pregnancy. This cross-sectional study describes the
      clinical OH status of a sample of pregnant women, examines relationships between
      sociodemographic factors and OH, behavioral factors and OH, and the influence of
      behavior on the relationships between sociodemographic clusters and OH. Baseline
      data were utilized from a pilot intervention study promoting OH during pregnancy.
      METHODS: Participants (n = 99), recruited from CenteringPregnancy((r)) prenatal
      care groups completed questionnaires addressing race/ethnicity, income,
      education, dental insurance, oral hygiene practices, and dental care utilization;
      and clinical examinations for periodontal probing depths (PD), bleeding on
      probing (BOP), plaque assessment, and visual detection of untreated decay. Chi
      squares and one-way anovas with Tukey's studentized range test of planned
      comparisons were conducted to examine bivariable relationships between both
      sociodemographic and behavioral characteristics to OH status. Multivariable
      logistic regression analyses tested whether the effects of sociodemographic
      variables on OH status might be mediated by behaviors, including self-reported
      oral hygiene and recent dental visits. RESULTS: Forty-five percent of the sample
      had untreated decay and the mean percentage of sites with BOP = 18%. Bivariable
      analyses of sociodemographic factors indicated that compared with Whites,
      Hispanic women had greater % of sites with: BOP, PD >=5 mm plus BOP, and Plaque
      Index (PI) scores of >=2, all P = 0.05; and greater untreated decay (Chi-square
      13.3, P < 0.001). Lower income was related to greater untreated decay (Chi-square
      7.6, P < 0.01). Compared with the highest education level, the lowest level group
      had higher % BOP, P < 0.05. Public dental insurance (versus private) was
      associated with greater % BOP, PD >=5 mm plus BOP, both P < 0.05, and greater
      untreated decay (Chi-square 16.9, P < 0.001). Regarding behaviors, lacking a past
      6-month dental visit was related to greater: BOP, PD >=5 mm plus BOP, and PI >=2
      (F range 6.2-8.7, P < 0.01-0.05); and greater untreated decay (Chi-square 12.0, P
      < 0.001). Self-reported optimal oral hygiene was related to lower % BOP and PD
      >=5 mm plus BOP (F range 4.5-6.7, both P < 0.05). Mediation analyses indicated
      that there were significant indirect effects of racial/ethnic differences on OH
      outcomes via having a recent dental visit (OR range 1.2-1.9). However,
      significant differences between the Hispanic and White groups remained.
      CONCLUSIONS: This study highlights sociodemographic disparities in clinical OH
      during pregnancy, the importance of dental care, and provides useful findings for
      tailoring interventions for expectant mothers and their infants.

PMID- 24117712
TI  - Outbreak of Streptococcus agalactiae infection in barcoo grunter, Scortum barcoo
      (McCulloch & Waite), in an intensive fish farm in China.

PMID- 24117713
TI  - Neurobiological consequences of acute footshock stress: effects on tyrosine
      hydroxylase phosphorylation and activation in the rat brain and adrenal medulla.
AB  - Stress activates selected neuronal systems in the brain and this leads to
      activation of a range of effector systems. Our aim was to investigate some of the
      relationships between these systems under basal conditions and over a 40-min
      period in response to footshock stress. Specifically, we investigated
      catecholaminergic neurons in the locus coeruleus (LC), ventral tegmental area and
      medial prefrontal cortex (mPFC) in the brain, by measuring tyrosine hydroxylase
      (TH) protein, TH phosphorylation and TH activation. We also measured the effector
      responses by measuring plasma adrenocorticotrophic hormone, corticosterone,
      glucose and body temperature as well as activation of adrenal medulla protein
      kinases, TH protein, TH phosphorylation and TH activation. The LC, ventral
      tegmental area and adrenal medulla all had higher basal levels of Ser19
      phosphorylation and lower basal levels of Ser31 phosphorylation than the mPFC,
      presumably because of their cell body versus nerve terminal location, while the
      adrenal medulla had the highest basal levels of Ser40 phosphorylation. Ser31
      phosphorylation was increased in the LC at 20 and 40 min and in the mPFC at 40
      min; TH activity was increased at 40 min in both tissues. There were significant
      increases in body temperature between 10 and 40 min, as well as increases in
      plasma adrenocorticotropic hormone at 20 min and corticosterone and glucose at 20
      and 40 min. The adrenal medulla extracellular signal-regulated kinase 2 was
      increased between 10 and 40 min and Ser31 phosphorylation was increased at 20 min
      and 40 min. Protein kinase A and Ser40 phosphorylation were increased only at 40
      min. TH activity was increased between 20 and 40 min. TH protein and Ser19
      phosphorylation levels were not altered in any of the brain regions or adrenal
      medulla over the first 40 min. These findings indicate that acute footshock
      stress leads to activation of TH in the LC, pre-synaptic terminals in the mPFC
      and adrenal medullary chromaffin cells, as well as changes in activity of the
      hypothalamic-pituitary-adrenal axis.

PMID- 24117714
TI  - Clinical-pathological analysis of hepatitis B virus recurrence after liver
      transplantation in Chinese patients.
AB  - BACKGROUND AND AIM: Liver transplantation (LT) for hepatitis B virus (HBV)
      related disease can be complicated by HBV recurrence. The aim of this study was
      to evaluate the risk factors, prophylaxis treatment, and histological
      characteristics of HBV recurrence after LT when using long-term, low-dose
      hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or
      entecavir [ETV]). METHODS: Retrospective data from 253 adult LT patients using
      long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment
      duration of 1-72 months, were collected from a single center in Beijing, China.
      Univariate analyses were conducted to determine the association among gender,
      age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA
      level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV
      recurrence in these patients. RESULTS: Overall, the HBV recurrence rate was 6.32%
      (16/253). There was no significant difference in the survival rate between the
      HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were:
      hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular
      carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence
      (16/169; mean treatment duration: 61.8 +/- 18.3 months). No HBV recurrence
      occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1
      +/- 15.9 months). Differences in rate of mortality and HBV recurrence were not
      significant between the two groups. CONCLUSIONS: LT is an effective treatment for
      HBV-related end-stage liver disease. The combination of ETV and intramuscular
      HBIG for HBV recurrence prophylaxis after LT was more effective than LAM,
      especially in Chinese patients with HBV recurrence risk factors.

PMID- 24117715
TI  - Giant cell angiofibroma or localized periorbital lymphedema?
AB  - Giant cell angiofibroma represents a rare soft tissue neoplasm with a
      predilection for the orbit. We recently encountered a mass removed from the lower
      eyelid of a 56-year-old female that histopathologically resembled giant cell
      angiofibroma. The process consisted of haphazardly arranged CD34-positive
      spindled and multinucleated cells within an edematous, densely vascular stroma.
      However, the patient had recently undergone laryngectomy and radiotherapy for a
      laryngeal squamous cell carcinoma. A similar mass had arisen on the contralateral
      eyelid, and both had developed several months post-therapy. Lymphedema of the
      orbit can present as tumor-like nodules and in some cases may share
      histopathologic features purported to be characteristic of giant cell
      angiofibroma. A relationship between giant cell angiofibroma and lymphedema has
      not been established, but our case suggests there may be one. The potential
      overlap of these two conditions should be recognized, as should other entities
      that may enter the differential diagnosis. 

PMID- 24117716
TI  - Trait correlation networks: a whole-plant perspective on the recently criticized
      leaf economic spectrum.

PMID- 24117717
TI  - Ketamine as a part of anaesthetic management in a dog with twiddler's syndrome.
AB  - An 11-year-old male German shepherd dog was referred for possible pacemaker
      implantation. A routine 6-lead electrocardiogram revealed a third-degree atrio
      ventricular block with a heart rate of 40 to 45 beats/minute. A transvenous
      pacemaker implantation procedure was scheduled. The dog was premedicated with 10
      ug/kg acepromazine and 5 mg/kg pethidine. A dose of 5 mg/kg ketamine and 0.2
      mg/kg diazepam were used for induction and isoflurane in O2 and a constant rate
      infusion of ketamine (20 to 30 ug/kg/minute) were administered for maintenance of
      general anaesthesia. Due to a twiddler's syndrome, the pacemaker had to be
      repositioned. For the second procedure, the same protocol was employed except for
      a lower dose of ketamine both for induction (3 mg/kg) and constant rate infusion
      (10 to 15 ug/kg/minute). Ketamine appeared to be useful for both management of
      anaesthesia and cardiac pacemaker implantation in the absence of a temporary
      pacemaker.

PMID- 24117718
TI  - Development of the 'Extreme Demand Avoidance Questionnaire' (EDA-Q): preliminary
      observations on a trait measure for Pathological Demand Avoidance.
AB  - BACKGROUND: Pathological Demand Avoidance (PDA) is a term increasingly used in
      the United Kingdom to describe children who obsessively resist everyday demands,
      going to extreme lengths to avoid these. There is debate about its relationship
      with both autism spectrum disorder (ASD) and oppositional defiant disorder (ODD).
      Unlike ASD, children with PDA are said to use socially manipulative avoidance
      strategies; and unlike ODD, they resort to extreme, embarrassing or age
      inappropriate behaviour. To date, there has been little research into PDA, and it
      remains contentious. Currently, there are no questionnaire instruments available
      to aid consistency in description. This study reports the development and
      preliminary validation of the 'Extreme Demand Avoidance Questionnaire' (EDA-Q),
      designed to quantify PDA traits based on parent-reported information. METHODS:
      The validation study involved data from 326 parents of children aged 5-17
      allocated to six groups based on information reported by parents about received
      diagnoses and behavioural difficulties: (a) typically developing children (N =
      102), (b) children with ASD without disruptive behaviour (N = 36), (c) children
      with ASD with disruptive behaviour (N = 48), (d) children for whom PDA was
      suspected by parents (irrespective of other diagnoses) (N = 67), (e) children who
      had, according to parents, been identified as having PDA by a health
      professional, irrespective of other diagnoses (N = 50), and (6) disruptive
      behaviour or behavioural problems without suspected/identified ASD or PDA (N =
      23). RESULTS: Although the Strengths and Difficulties Questionnaire (SDQ) did not
      differentiate PDA from those with ASD plus disruptive behaviour; score on the EDA
      Q was significantly higher in PDA than all comparison groups. ROC analysis
      indicated good sensitivity (.80) and specificity (.85). Across all case groups,
      females scored higher than males on the EDA-Q. Separate cut-off scores were
      identified for older and younger age-groups. CONCLUSIONS: Our findings highlight
      the potential utility of the EDA-Q to assist the identification of this unusual
      profile for future research.

PMID- 24117719
TI  - Lipoprotein N-acyl transferase (Lnt1) is dispensable for protein O-mannosylation
      by Streptomyces coelicolor.
AB  - A protein glycosylation system related to that for protein mannosylation in yeast
      is present in many actinomycetes. This system involves polyprenyl phosphate
      mannose synthase (Ppm), protein mannosyl transferase (Pmt), and lipoprotein N
      acyl transferase (Lnt). In this study, we obtained a series of mutants in the ppm
      (sco1423), lnt1 (sco1014), and pmt (sco3154) genes of Streptomyces coelicolor,
      which encode Ppm, Lnt1, and Pmt, to analyze their requirement for glycosylation
      of the heterologously expressed Apa glycoprotein of Mycobacterium tuberculosis.
      The results show that both Ppm and Pmt were required for Apa glycosylation, but
      that Lnt1 was dispensable for both Apa and the bacteriophage phiC31 receptor
      glycosylation. A bacterial two-hybrid assay revealed that contrary to M.
      tuberculosis, Lnt1 of S. coelicolor does not interact with Ppm. The D2 catalytic
      domain of M. tuberculosisPpm was sufficient for complementation of an S.
      coelicolor double mutant lacking Lnt1 and Ppm, both for Apa glycosylation and for
      glycosylation of phiC31 receptor. On the other hand, M. tuberculosisPmt was not
      active in S. coelicolor, even when correctly localized to the cytoplasmic
      membrane, showing fundamental differences in the requirements for Pmt activity in
      these two species. 

PMID- 24117720
TI  - Primary irritation index and safety zone of cosmetics: retrospective analysis of
      skin patch tests in 7440 Korean women during 12 years.
AB  - BACKGROUND: Cosmetics are products used over long periods by the public, and
      their safety is very important. Several types of human tests are used widely for
      the evaluation of cosmetics including single patch tests, in-use tests, human
      repeated insult patch test (HRIPT). However, there is no clear and well-defined
      published objective and standardized criteria for primary skin irritation in
      regard to the large variety of cosmetic products. METHODS: This study analysed
      human patch tests conducted from May 2001 to December 2012 with 4606 materials of
      prototype or finished cosmetic products on 7440 normal Korean women aged 18-60
      years. The tested products were patched under occlusion for 24 or 48 h, and skin
      tolerance was assessed twice at 30 min and 24 h after patch removal using a 5
      step scale according to the CTFA guidelines. RESULTS: Human patch tests for
      cosmetics were performed of 4606 cases, and 30-33 subjects participated in each
      case. The response in each case was calculated based on total subject number,
      skin reaction intensity and the number of respondents. The calculated response
      was standardized using the z-score, and a safety zone was provided in terms of
      human primary irritation in accordance with the human skin reaction evaluation
      criteria and usage or formula of cosmetics. CONCLUSIONS: This study established
      the safety criteria for irritation in the cosmetics field.

PMID- 24117721
TI  - Adolescents and young adults with physical illness: a comparative study of
      psychological distress.
AB  - AIM: There is limited research investigating the relationship between physical
      illness and psychological distress among adolescents during the transition to
      young adulthood. This study examined risk for clinically relevant psychological
      distress over a 10-year period comparing adolescents and young adults with asthma
      or epilepsy with healthy controls. METHODS: This research used data from the
      British Household Panel Survey (1991-2009) to compare healthy 16 to 25-year-olds
      (n = 7342) with individuals with asthma (n = 1798) and epilepsy (n = 117).
      Psychological distress was measured using the 12-item General Health
      Questionnaire. Controlling for sociodemographic characteristics, generalised
      linear modelling was used to examine risk of psychological distress over time.
      RESULTS: Using healthy individuals as the reference category, prevalence ratios
      for psychological distress among individuals with asthma and epilepsy ranged from
      1.1 to 2.7 and 2.3 to 7.0, respectively. Controlling for potential confounding
      factors (sex, marital status, employment status, income), risk for psychological
      distress was increased among individuals with asthma (OR = 1.94, p < 0.0001) or
      epilepsy (OR = 3.45, p = 0.0002) compared with healthy controls during the follow
      up. CONCLUSION: Recognizing the increased risk among individuals with physical
      illness, paediatric and adult health professionals are well positioned to
      facilitate successful transition to adult health services and prevent or reduce
      psychological distress in this vulnerable population.

PMID- 24117722
TI  - A rare case of sudden death due to hypotension during cesarean section in a woman
      suffering from pheochromocytoma and neurofibromatosis.
AB  - Sudden death following acute hypotension due to an undiagnosed pheochromocytoma
      (PHEO) is a rare event. Moreover, histopathology of the myocardium in such cases
      is rarely reported. We present a case of a woman who died during delivery. A 37
      year-old parturient, who was 38 weeks pregnant, suffering from neurofibromatosis
      underwent a cesarean section following peridural anesthesia. Acute hypotension,
      acute intra-operative pulmonary edema and supraventricular paroxysmal
      tachyarrhythmia occurred during delivery, followed by death. The autopsy revealed
      the presence of a PHEO, confirmed immunohistochemically with chromogranin-A
      (CgA), CD20 antibody (L26), anti-Keratocan antibody (KER-1) and neuron-specific
      enolase (NSE), and a PHEO-induced cardiomyopathy. The physiopathology of both
      stress-induced cardiomyopathy and PHEO-induced cardiomyopathy, as well as the
      role of anesthesia in provoking the death, are discussed. The association of an
      undiagnosed PHEO with neurofibromatosis as the cause of sudden death in pregnancy
      is an obstetric urgency that raises forensic pathology issues.

PMID- 24117723
TI  - Red blood cell alloimmunization in sickle cell disease and in thalassaemia:
      current status, future perspectives and potential role of molecular typing.
AB  - Red blood cell (RBC) transfusions are a milestone in the treatment for sickle
      cell anaemia (SSA) and for thalassaemia. RBC alloimmunization remains a major
      challenge of chronic transfusion therapy, and it can lead to adverse life
      threatening events. The alloimmunization risk could depend on multiple factors
      such as the number of transfusions and, most of all, the genetic background.
      Different ethnic groups are predisposed to immunization because of a significant
      degree of RBC antigenic mismatch between donor and recipient. There is no
      universal agreement and standards for the most appropriate selection of RBC units
      in chronically transfused subjects. Current practice only deals with
      compatibility of ABO, Rh and K antigens. Molecular RBC antigenic matching
      extended to other blood group systems is an innovative strategy to ensure a
      better quality and effectiveness of transfusion therapy. 

PMID- 24117724
TI  - In vivo study of ethanol-activated brain protein kinase A: manipulations of Ca2+
      distribution and flux.
AB  - BACKGROUND: The cAMP-dependent protein kinase (PKA) signaling transduction
      pathway has been shown to play an important role in the modulation of several
      ethanol (EtOH)-induced behavioral actions. In vivo, short-term exposure to EtOH
      up-regulates the cAMP-signaling cascade. Interestingly, different Ca(2+) 
      dependent cAMP-PKA cascade mediators play a critical role in the neurobehavioral
      response to EtOH, being of special relevance to the Ca(2+) -dependent adenylyl
      cyclases 1 and 8. We hypothesize an intracellular PKA activation elicited by EtOH
      administration, which may be regulated by a Ca(2+) -dependent mechanism as an
      early cellular response. Thus, the present work aims to explore the role of
      Ca(2+) (internal and external) on the EtOH-activated PKA cascade. METHODS: Swiss
      male mice received an intraperitoneal injection of EtOH (0 or 4 g/kg), and brains
      were dissected following a temporal pattern (7, 15, 30, 45, 90, or 120 minutes).
      Either the enzymatic PKA activity or its fingerprint was analyzed on different
      brain areas (cortex, hypothalamus, hippocampus, and striatum). To explore the
      role of Ca(2+) on the EtOH-activated PKA cascade, mice were pretreated with
      diltiazem (0 or 20 mg/kg), dantrolene (0 or 5 mg/kg), or 3,7-Dimethyl-1-(2
      propynyl)xanthine (0 or 1 mg/kg) 30 minutes before EtOH (4 g/kg) administration.
      After 45 minutes of EtOH administration, brains were removed and dissected to
      measure the PKA activity or its fingerprint. RESULTS: Results from these
      experiments showed an EtOH-dependent activation of PKA in different brain areas.
      Manipulations involving a disruption of intracellular Ca(2+) release from the
      endoplasmic reticulum resulted in a decreased EtOH-induced activation of PKA. On
      the contrary, extracellular-to-cytoplasm Ca(2+) manipulations did not prevent the
      PKA activation by EtOH. CONCLUSIONS: Altogether, these results show the critical
      role of stored Ca(2+) as an intracellular mediator of different neurobiological
      actions of EtOH and provide further evidence of a possible new target for EtOH
      within the central nervous system.

PMID- 24117725
TI  - Dietary phosphorus, serum phosphorus, and cardiovascular disease.
AB  - Recent epidemiologic studies have linked higher serum phosphorus concentrations
      to cardiovascular disease (CVD) events and mortality. This association has been
      identified in the general population and in those with chronic kidney disease
      (CKD). The risk of adverse outcomes appears to begin with phosphorus
      concentrations within the upper limit of the normal reference range. Multiple
      experimental studies have suggested pathogenetic mechanisms that involve direct
      and indirect effects of high phosphorus concentrations to explain these
      associations. Drawing from these observations, guideline-forming agencies have
      recommended that serum phosphorus concentrations be maintained within the normal
      reference range in patients with CKD and that dietary phosphorus restriction or
      use of intestinal phosphate binders should be considered to achieve this goal.
      However, outside the dialysis population, the links between dietary phosphorus
      intake and serum phosphorus concentrations, and dietary phosphorus intake and CVD
      events, are uncertain. With specific reference to the nondialysis populations,
      this review discusses the available data linking dietary phosphorus intake with
      serum phosphorus concentrations and CVD events. 

PMID- 24117726
TI  - Endothelin-1 directs airway remodeling and hyper-reactivity in a murine asthma
      model.
AB  - BACKGROUND: The current paradigm describing asthma pathogenesis recognizes the
      central role of abnormal epithelial function in the generation and maintenance of
      the disease. However, the mechanisms responsible for the initiation of airway
      remodeling, which contributes to decreased lung function, remain elusive.
      Therefore, we aimed to determine the role of altered pulmonary gene expression in
      disease inception and identify proremodeling mediators. METHODS: Using an
      adenoviral vector, we generated mice overexpressing smad2, a TGF-beta and activin
      A signaling molecule, in the lung. Animals were exposed to intranasal ovalbumin
      (OVA) without systemic sensitization. RESULTS: Control mice exposed to inhaled
      OVA showed no evidence of pulmonary inflammation, indices of remodeling, or
      airway hyper-reactivity. In contrast, local smad2 overexpression provoked airway
      hyper-reactivity in OVA-treated mice, concomitant with increased airway smooth
      muscle mass and peribronchial collagen deposition. Pulmonary eosinophilic
      inflammation was not evident, and there was no change in serum IgE or IgG1
      levels. The profound remodeling changes were not mediated by classical pro
      inflammatory Th2 cytokines. However, uric acid and interleukin-1beta levels in
      the lung were increased. Epithelial-derived endothelin-1 and fibroblast growth
      factor were also augmented in smad2-expressing mice. Blocking endothelin-1
      prevented these phenotypic changes. CONCLUSIONS: Innate epithelial-derived
      mediators are sufficient to drive airway hyper-reactivity and remodeling in
      response to environmental insults in the absence of overt Th2-type inflammation
      in a model of noneosinophilic, noninflammed types of asthma. Targeting potential
      asthma therapies to epithelial cell function and modulation of locally released
      mediators may represent an effective avenue for therapeutic design.

PMID- 24117727
TI  - Introduction: Celebrating Emeritus Scientia Professor Eugenie R Lumbers AM and
      Professor Caroline McMillen.

PMID- 24117729
TI  - The Association of British Clinical Diabetologists nationwide exenatide and
      liraglutide audits suggest a low incidence of acute pancreatitis. Response to
      Robson. Incretins and pancreatitis--what happens next? A personal viewpoint.

PMID- 24117728
TI  - Paediatric gastroenterology evaluation of overweight and obese children referred
      from primary care for suspected non-alcoholic fatty liver disease.
AB  - BACKGROUND: Screening overweight and obese children for non-alcoholic fatty liver
      disease (NAFLD) is recommended by paediatric and endocrinology societies.
      However, gastroenterology societies have called for more data before making a
      formal recommendation. AIM: To determine whether the detection of suspected NAFLD
      in overweight and obese children through screening in primary care and referral
      to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. METHODS:
      Information generated in the clinical evaluation of 347 children identified with
      suspected NAFLD through screening in primary care and referral to paediatric
      gastroenterology was captured prospectively. Diagnostic outcomes were reported.
      The diagnostic performance of two times the upper limit of normal (ULN) for
      alanine aminotransferase (ALT) was assessed. RESULTS: Non-alcoholic fatty liver
      disease was diagnosed in 55% of children identified by screening and referral.
      Liver disease other than NAFLD was present in 18% of those referred. Autoimmune
      hepatitis was the most common alternative diagnosis. Children with NAFLD had
      significantly (P < 0.05) higher screening ALT (98 +/- 95) than children with
      liver disease other than NAFLD (86 +/- 74). Advanced fibrosis was present in 11%
      of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN
      had a sensitivity of 57% and a specificity of 71%. CONCLUSIONS: Screening of
      overweight and obese children in primary care for NAFLD with referral to
      paediatric gastroenterology has the potential to identify clinically relevant
      liver pathology. Consensus is needed on how to value the risk and rewards of
      screening and referral, to identify children with liver disease in the most
      appropriate manner.

PMID- 24117730
TI  - Evaluations versus expectations: children's divergent beliefs about resource
      distribution.
AB  - Past research reveals a tension between children's preferences for egalitarianism
      and ingroup favoritism when distributing resources to others. Here we investigate
      how children's evaluations and expectations of others' behaviors compare. Four-
      to 10-year-old children viewed events where individuals from two different groups
      distributed resources to their own group, to the other group, or equally across
      groups. Groups were described within a context of intergroup competition over
      scarce resources. In the Evaluation condition, children were asked to evaluate
      which resource distribution actions were nicer. In the Expectation condition,
      children were asked to predict which events were more likely to occur. With age,
      children's evaluations and expectations of others' actions diverged: Children
      evaluated egalitarian actions as nicer yet expected others to behave in ways that
      benefit their own group. Thus, children's evaluations about the way human social
      actors should behave do not mirror their expectations concerning those
      individuals' actions. 

PMID- 24117731
TI  - Postoperative emesis after laparoscopic pyloromyotomy in infantile hypertrophic
      pyloric stenosis.
AB  - AIM: This study aimed to determine the causes of postoperative emesis (PE) in
      neonates with infantile hypertrophic pyloric stenosis (IHPS) after laparoscopic
      pyloromyotomy (LP). METHODS: Retrospective review of the hospital database for
      infants with IHPS managed between 2000 and 2010 was performed. Relevant data were
      collected from the clinical records in the Medocs((r)) system and used for
      statistical analysis. RESULTS: During the 10-year period, 95 patients with IHPS
      were identified and 43 (36 boys and seven girls) fulfilled the inclusion
      criteria. PE occurred in 21 infants (48.8%), of which nine presented with
      manifestations of enteric infections, with confirmed diagnosis in four. PE was
      significantly higher in the fast track feeding protocol (FTFP) group 12/15
      compared with the conventional slow feeding protocol (CSFP) group 8/21 (p =
      0.019). Gastro-oesophageal reflux (GER) confirmed by 24-h impedance monitoring
      was responsible for PE in three. Operative revision for suspected incomplete
      pyloromyotomy was performed in five infants. However, incomplete myotomy could
      only be confirmed in two infants during surgery. CONCLUSION: Postoperative emesis
      in IHPS after LP requires careful evaluation as it can be a result of enteric
      viral infections, aggressive feeding protocols or GER. Decisions to perform
      reoperations for incomplete myotomy after LP due to PE are challenging.

PMID- 24117732
TI  - Bayesian classifiers applied to the Tennessee Eastman process.
AB  - Fault diagnosis includes the main task of classification. Bayesian networks (BNs)
      present several advantages in the classification task, and previous works have
      suggested their use as classifiers. Because a classifier is often only one part
      of a larger decision process, this article proposes, for industrial process
      diagnosis, the use of a Bayesian method called dynamic Markov blanket classifier
      that has as its main goal the induction of accurate Bayesian classifiers having
      dependable probability estimates and revealing actual relationships among the
      most relevant variables. In addition, a new method, named variable ordering
      multiple offspring sampling capable of inducing a BN to be used as a classifier,
      is presented. The performance of these methods is assessed on the data of a
      benchmark problem known as the Tennessee Eastman process. The obtained results
      are compared with naive Bayes and tree augmented network classifiers, and confirm
      that both proposed algorithms can provide good classification accuracies as well
      as knowledge about relevant variables. 

PMID- 24117733
TI  - Phosphoproteomic evaluation of pharmacological inhibition of leucine-rich repeat
      kinase 2 reveals significant off-target effects of LRRK-2-IN-1.
AB  - Genetic mutations in leucine-rich repeat kinase 2 (LRRK2) have been linked to
      autosomal dominant Parkinson's disease. The most prevalent mutation, G2019S,
      results in enhanced LRRK2 kinase activity that potentially contributes to the
      etiology of Parkinson's disease. Consequently, disease progression is potentially
      mediated by poorly characterized phosphorylation-dependent LRRK2 substrate
      pathways. To address this gap in knowledge, we transduced SH-SY5Y neuroblastoma
      cells with LRRK2 G2019S via adenovirus, then determined quantitative changes in
      the phosphoproteome upon LRRK2 kinase inhibition (LRRK2-IN-1 treatment) using
      stable isotope labeling of amino acids in culture combined with phosphopeptide
      enrichment and LC-MS/MS analysis. We identified 776 phosphorylation sites that
      were increased or decreased at least 50% in response to LRRK2-IN-1 treatment,
      including sites on proteins previously known to associate with LRRK2.
      Bioinformatic analysis of those phosphoproteins suggested a potential role for
      LRRK2 kinase activity in regulating pro-inflammatory responses and neurite
      morphology, among other pathways. In follow-up experiments, LRRK2-IN-1 inhibited
      lipopolysaccharide-induced tumor necrosis factor alpha (TNFalpha) and C-X-C motif
      chemokine 10 (CXCL10) levels in astrocytes and also enhanced multiple neurite
      characteristics in primary neuronal cultures. However, LRRK2-IN-1 had almost
      identical effects in primary glial and neuronal cultures from LRRK2 knockout
      mice. These data suggest LRRK2-IN-1 may inhibit pathways of perceived LRRK2
      pathophysiological function independently of LRRK2 highlighting the need to use
      multiple pharmacological tools and genetic approaches in studies determining
      LRRK2 function.

PMID- 24117734
TI  - Congenital peribronchial myofibroblastic tumour with features of maturation in
      the older infant: report of two cases with a literature review.

PMID- 24117735
TI  - Removal of exogenous prion infectivity in leukoreduced red blood cells unit by a
      specific filter designed for human transfusion.
AB  - BACKGROUND: Five cases of variant Creutzfeldt-Jakob disease (vCJD) infections
      were attributed to infusion of contaminated blood components, turning to real the
      interhuman transmissibility of this prion disease from asymptomatic carriers.
      Preventive policies rely on exclusion from blood donation and benefit of
      leukoreduction initially implemented against leukotropic viruses. In the absence
      of available antemortem diagnostic tests, the updated prevalence of silent vCJD
      infections (1/2000 in the United Kingdom) urges the necessity to enforce blood
      safety with more efficient active measures able to remove the remaining
      infectivity. STUDY DESIGN AND METHODS: Several affinity resins were demonstrated
      to reduce high levels of brain-spiked infectivity from human leukoreduced red
      blood cells (L-RBCs). One was integrated in a device adapted to field constraints
      (volumes, duration) of human transfusion. We assessed here the ability of the
      resulting removal filter, termed P-Capt, to remove infectivity from human L-RBC
      units spiked with scrapie-infected hamster brain (>=10,000 infectious units/mL),
      through inoculation of hamsters with pre- and post-blood filtration samples.
      RESULTS: Incubation periods of recipient animals suggest around a 3-log removal
      of brain-derived prion infectivity by filtration through the P-Capt. CONCLUSION:
      On brain-derived spiked infectivity, the P-Capt filter provided a performance
      similar to the resin packed in columns used for initial proof-of-concept studies,
      suggesting an appropriate scale-up to efficiently remove infectivity from an
      individual human blood bag. According to the ability of resin to completely
      remove apparent endogenous infectivity from hamster leukoreduced blood, the
      implementation of such a filter, now commercially available, might seriously
      improve blood safety toward prions.

PMID- 24117736
TI  - Methylisothiazolinone is categorised as a strong sensitiser in the Murine Local
      Lymph Node Assay.

PMID- 24117737
TI  - Recommendation to include methylisothiazolinone in the European baseline patch
      test series--on behalf of the European Society of Contact Dermatitis and the
      European Environmental and Contact Dermatitis Research Group.
AB  - BACKGROUND: Methylisothiazolinone (MI) is used as a preservative in occupational
      and household products, and cosmetics. It is a part of the preparation of
      methylchloroisothiazolinone (MCI)/MI, which is patch tested in water in the
      European baseline series. However, this preparation fails to detect a significant
      percentage of allergic contact reactions to MI. OBJECTIVES: To investigate
      whether a separate test preparation with MI should be included in the European
      baseline series. METHODS: Literature survey. RESULTS: In consecutively tested
      dermatitis patients, the contact allergy rate for MI varies between 0.6% and 6%,
      with a marked increase in recent years. The contact allergy rate for MI alone,
      not detected with MCI/MI, varies between 0% and 1.6%. Most cases are relevant, as
      shown by repeated open application test studies, and are mainly related to
      exposure from cosmetic products. CONCLUSIONS: Owing to the increase in contact
      allergy to MI not detected with MCI/MI, it is recommended that MI in water at
      2000 ppm be included in the European baseline series. With the Finn Chamber((r))
      (diameter, 8 mm) technique, a volume of 15 ul should be applied, giving a dose of
      60 ug/cm(2).

PMID- 24117738
TI  - Methylisothiazolinone contact allergy--growing epidemic.
AB  - BACKGROUND: The prevalence of contact allergy to the isothiazolinone preservative
      methylchloroisothiazolinone (MCI) in combination with methylisothiazolinone (MI)
      and MI alone has increased in the last couple of years. OBJECTIVES: To
      investigate the prevalence of contact allergy to MI, MCI/MI and
      benzisothiazolinone (BIT) among patch tested patients at Gentofte Hospital, as
      well as the use of MI in cosmetic products. METHODS: Patients patch tested with
      either MI, MCI/MI or BIT from 2010 to 2012 were included in the study. The
      MOAHLFA index was registered in all patch tested patients, and relevant exposures
      were determined in patients with an isothiazolinone allergy. In a market survey,
      the ingredient labels of cosmetic products were investigated for MI content.
      RESULTS: The prevalence of MI and MCI/MI contact allergy increased significantly
      from 2010 to 2012: from 2.0% to 3.7% for MI (n = 2766), and from 1.0% to 2.4% for
      MCI/MI (n = 2802). MI-allergic patients had occupational, hand and face
      dermatitis significantly more often, and were aged > 40 years. Cosmetics were the
      most common substances causing relevant exposure found in both MCI/MI-allergic
      and MI-allergic patients. MI was found in 3.3% of cosmetics on the Danish retail
      market. CONCLUSIONS: The increase in MI contact allergy is alarming, and urgent
      action is needed.

PMID- 24117739
TI  - Consumer leather exposure: an unrecognized cause of cobalt sensitization.
AB  - BACKGROUND: A patient who had suffered from persistent generalized dermatitis for
      7 years was diagnosed with cobalt sensitization, and his leather couch was
      suspected as the culprit, owing to the clinical presentation mimicking allergic
      chromium dermatitis resulting from leather furniture exposure. MATERIALS AND
      METHODS: The cobalt spot test, X-ray fluorescence, inductively coupled plasma
      mass spectrometry and scanning electron microscopy were used to determine cobalt
      content and release from the leather couch that caused the dermatitis and from 14
      randomly collected samples of furniture leather. RESULTS: The sample from the
      patient's leather couch, but none of the 14 random leather samples, released
      cobalt in high concentrations. Dermatitis cleared when the patient stopped using
      his couch. CONCLUSIONS: Cobalt is used in the so-called pre-metallized dyeing of
      leather products. Repeated studies have found high levels of cobalt
      sensitization, but not nickel sensitization, in patients with foot dermatitis. We
      raise the possibility that cobalt may be widely released from leather items, and
      advise dermatologists to consider this in patients with positive cobalt patch
      test reactions.

PMID- 24117740
TI  - Patch testing and sensitization to multiple drugs.
AB  - BACKGROUND: Adverse drug reactions pose an increasing diagnostic challenge in
      hospitals and in outpatient clinics. When consecutive or repeated allergic drug
      eruptions are suspected, patch testing is a useful diagnostic tool for
      determining the causative drugs. OBJECTIVES: The aim of the study was to identify
      patient cases with multiple delayed-type drug sensitizations by using patch
      testing. METHODS: Eight hundred and eleven patients with suspected drug allergy
      were patch tested during a 9-year period. RESULTS: Multiple delayed drug
      sensitizations were found in 12% of those patients with positive results in drug
      patch testing. CONCLUSIONS: Drug patch testing is useful in cutaneous adverse
      drug reactions where multiple drugs are suspected. Multiple drug sensitizations
      can be found in a proportion of patients who have delayed drug allergies. In
      addition to drug reactions with eosinophilia and systemic symptoms, these
      patients may have repeated exanthemas or contact dermatitis.

PMID- 24117741
TI  - Allergic contact dermatitis caused by methylisothiazolinone from different
      sources, including 'mislabelled' household wet wipes.

PMID- 24117742
TI  - Allergic contact dermatitis caused by sorbitan sesquioleate imitating severe
      glove dermatitis in a patient with filaggrin mutation.

PMID- 24117743
TI  - Contact dermatitis with systemic reactions caused by cetearyl isononanoate.

PMID- 24117744
TI  - Contact allergy from metalworking fluid traced to tall oil fatty acids
      monoethanolamide.

PMID- 24117745
TI  - Allergic contact cheilitis caused by carnauba wax in a lip balm.

PMID- 24117746
TI  - Allergic contact dermatitis caused by phenylethyl resorcinol [4-(1-phenylethyl)
      1,3-benzenediol], a skin-lightening agent in cosmetics.

PMID- 24117747
TI  - Allergic contact dermatitis caused by panthenol in a child.

PMID- 24117748
TI  - Molecular analysis of a case of renal cell carcinoma with t(6;11)(p21;q12)
      reveals a link to a lysosome-like structure.

PMID- 24117749
TI  - Conservative biopsy excision and management of a large iris melanoma.

PMID- 24117750
TI  - Resection of huge retrosternal goiter through a novel combined cervical and robot
      assisted approach.
AB  - A 53-year-old man was referred to our department with a history of cough,
      especially at night, for 3 months. He was found to have a huge retrosternal
      goiter. We applied a novel combined cervical and robot-assisted approach to
      resect this difficult goiter. Using the da Vinci robot system, the intrathoracic
      part of the goiter was dissected and mobilized completely from the mediastinum to
      the inlet of the thorax. The dissected part of the goiter was left in the thorax.
      A right cervical half-collar incision about 6 cm was then performed. The goiter
      was finally removed from the neck incision. Histopathologic examination reported
      a multinodular goiter. By the method shown in the case, resection of huge
      retrosternal goiters through a combined cervical and robot-assisted approach is
      feasible and safe. This method provides an alternative option to the more
      invasive traditional approaches. 

PMID- 24117751
TI  - Inflammatory myofibroblastic tumour in the nasal cavity of a dog.
AB  - A 4.5-year-old, female neutered Leonberger was presented with a 2-month history
      of sneezing, nasal discharge and epistaxis. A presumptive diagnosis of nasal
      aspergillosis was made based on a suspected (fungal) granuloma on rhinoscopic
      examination and fungal hyphae on cytological examination. A poor response to
      targeted therapy was observed and computed tomography 16 months after initial
      presentation revealed a progressive, locally invasive mass lesion.
      Histopathological and immunohistochemical analysis of deep surgical biopsies
      revealed a spindle cell population and a plasma cell rich inflammatory
      infiltrate, with diffuse expression of vimentin, supporting a diagnosis of
      inflammatory myofibroblastic tumour. Complete resolution of the nasal discharge
      and reduced sneezing frequency was reported 9 months post-surgical debridement
      via rhinotomy. To the authors' knowledge, this is the first report of IMT in the
      nasal cavity of a dog. IMT should be considered when presented with a nasal mass
      lesion, particularly if histopathological features and clinical course are
      inconsistent. 

PMID- 24117752
TI  - The meaning of ethically charged encounters and their possible influence on
      professional identity in Norwegian public health nursing: a phenomenological
      hermeneutic study.
AB  - BACKGROUND: In today's health care, new health reforms focus on market values and
      demands of efficiency influence health workers' professional practice. Norwegian
      public health nurses work mainly with healthy populations, but the children,
      families and young people they meet can be in vulnerable and even dependent
      situations. Strategies in coping with ethically challenging encounters can be
      important for the identity of the profession. AIM: The aim of the study was to
      illuminate public health nurses' experiences of being in ethically charged
      encounters and to reflect upon how these experiences can influence their
      professional identity. METHOD: A purposive sample of 23 Norwegian public health
      nurses with experience ranging from 0.5 to 25 years narrated about their work
      related experiences. The interviews were interpreted with a phenomenological
      hermeneutic method inspired by the philosophy of Paul Ricoeur. FINDINGS: Four
      themes were identified: feeling responsible, being committed, feeling confident
      and feeling inadequate. These experiences were related to both work and private
      life and involved an emotional commitment to the well-being of children, young
      people and families. CONCLUSION: On the basis of the findings, it can be
      estimated that PHNs are committed to their work, and defending children's rights
      is a strong driving force. Responsibility for service users is a deciding factor
      that can overshadow institutional demands. It seems as if value conflicts
      mobilised courage which is essential in maintaining moral strength. This is in
      turn important for a strong professional identity and can have positive
      implications for the quality of public health nursing work.

PMID- 24117753
TI  - The role of DNA-stained currency in gang robberies within the United Kingdom.
AB  - Cash-and-valuables-in-transit (CViT) robberies have become a substantial problem
      especially in the current global economy. Over L19.4 million were stolen in 2008
      and L17.1 million in 2009 in the United Kingdom alone. The transportation of cash
      and valuable items between financial institutions has long been a target of
      robberies in the U.K. After a robbery has occurred, police collect evidence in
      the form of ink-stained currency. These stained notes are submitted for analysis.
      Samples are subjected to polymerase chain reaction in order to amplify any
      possible botanically derived DNA markers present on the notes. After
      amplification, capillary electrophoresis allows for the deciphering of the "DNA
      profile." The DNA profile is then linked to a particular cash box, and this
      information is compared with records of whether or not that box had been stolen.
      The cases below are three such instances where botanically marked currency was
      used to help solve robberies. 

PMID- 24117754
TI  - Functional outcomes of child and adolescent oppositional defiant disorder
      symptoms in young adult men.
AB  - BACKGROUND: Oppositional defiant disorder(ODD) is considered to be a disorder of
      childhood, yet evidence suggests that prevalence rates of the disorder are stable
      into late adolescence and trajectories of symptoms persist into young adulthood.
      Functional outcomes associated with ODD through childhood and adolescence include
      conflict within families, poor peer relationships, peer rejection, and academic
      difficulties. Little examination of functional outcomes in adulthood associated
      with ODD has been undertaken. METHOD: Data for the present analyses come from a
      clinic referred sample of 177 boys aged 7-12 followed up annually to age 18 and
      again at age 24. Annual parental report of psychopathology through adolescence
      was used to predict self-reported functional outcomes at 24. RESULTS: Controlling
      for parent reported symptoms of attention deficit hyperactivity disorder (ADHD),
      Conduct disorder (CD), depression and anxiety, ODD symptoms from childhood
      through adolescence predicted poorer age 24 functioning with peers, poorer
      romantic relationships, a poorer paternal relationship, and having nobody who
      would provide a recommendation for a job. CD symptoms predicted workplace
      problems, poor maternal relationship, lower academic attainment, and violent
      injuries. Only parent reported ODD symptoms and child reported CD symptoms
      predicted a composite of poor adult outcomes. CONCLUSION: Oppositional defiant
      disorder is a disorder that significantly interferes with functioning,
      particularly in social or interpersonal relationships. The persistence of
      impairment associated with ODD into young adulthood calls for a reconsideration
      of ODD as a disorder limited to childhood.

PMID- 24117755
TI  - Physiological effect of olfactory stimuli inhalation in humans: an overview.
AB  - The importance of odorants in human life has long been recognized. Literature
      contains different approaches of physiological and psychological effects of
      odorant compounds, fragrances and essential oils. This work discusses odorants
      inhalation effect, based on an overview of major studies in humans. Beneficial
      effect of fragrances is mainly related to human behaviour. Studies document
      odorants influence in sympathetic and parasympathetic nervous systems, and
      neurophysiological brain activity. Moreover, odours compounds can act on the
      neuroendocrine system, neurotransmitters and neuromodulators, influencing
      psychological behaviour as well as body function. Odorant inhalation modulates
      physiological pathways, and in some cases, results in skin function regulation.
      The mechanism is incompletely elucidated. These findings suggest that olfactory
      system plays a role in central nervous system function beyond that of smell. In
      this overview, it was observed that odour compounds influenced stress biomarkers,
      dehydroepiandrosterone, oxidative stress, estradiol, dopamine, cutaneous barrier,
      sebum secretion and cutaneous immune system in humans. Some can be related with
      skin function. As the skin is associated with an extensive biochemical cascade
      and has complex mechanisms, studies have far to go, as there are processes not
      yet investigated related to skin that may be affected through olfaction. Future
      researches are needed to further understand and describe the mechanisms of action
      of physiological effects in fragrance compounds. 

PMID- 24117756
TI  - Alcohol dependence and suicide-related ideation/behaviors in an Israeli household
      sample, with and without major depression.
AB  - BACKGROUND: Suicide-related ideation and behaviors (SRIB) are associated with
      both alcohol disorders and major depressive disorder (MDD). The objective of this
      study was to evaluate the relationship of alcohol dependence (AD) and major
      depression to the risk for lifetime SRIB. METHODS: Data from a community-based
      sample of 1,237 adult Israeli lifetime drinkers assessed with reliable diagnostic
      measures were analyzed using logistic regression. RESULTS: Lifetime SRIB was
      reported in 4.7% and was more prevalent among participants with AD (9.0%) than
      among those without AD (4.1%); p-value = 0.01. Although both AD and major
      depression were associated with SRIB (AD: OR 2.2, 95% CI 1.1 to 4.4; MDD: OR
      11.4, 95% CI = 6.4 to 20.4), joint analysis showed that AD without MDD increased
      risk for SRIB as compared to those without AD or MDD (OR 3.1, 95% CI 1.1 to 9.1),
      but AD did not increase risk among those with MDD (OR 1.1, 95% CI 0.4 to 2.7).
      Among those with AD, the severity of subclinical depressive symptoms was
      associated with increased SRIB. CONCLUSIONS: These findings show that AD
      increases risk for SRIB among individuals without a history of major depression.
      Suicidal tendencies may be undetected and underdiagnosed in this group because of
      the absence of major depression and therefore left untreated. These findings
      should be considered when adopting suicide prevention or treatment strategies for
      this high-risk subpopulation.

PMID- 24117757
TI  - Hexamitiasis leads to lower metabolic rates in rainbow trout Oncorhynchus mykiss
      (Walbaum) juveniles.
AB  - This study assessed the effects of Hexamita salmonis (Moore) on metabolism of
      rainbow trout Oncorhynchus mykiss (Walbaum) and its effect on the host's
      susceptibility to infectious pancreatic necrosis virus (IPNV) after antiparasitic
      treatment. Rainbow trout naturally infected with H. salmonis were treated with 10
      mg metronidazole kg fish(-1) per day, and their physiological recovery was
      assessed through measuring resting metabolism on the 7th, 14th, 21st and 28th day
      after treatment. In addition, we exposed the naive fish to H. salmonis and
      measured the resting metabolism (oxygen consumption as mg O2 kg(-1) per hour) on
      the 10th, 20th and 30th day after the exposure to assess the variation in
      metabolic rates after infection. Significantly lower rates of metabolic activity
      (P < 0.05) were anticipated 20 days after infection with H. salmonis compared
      with the fish infected with H. salmonis for 10 days or with the parasite-free
      fish. Similarly, the treated fish needed about 20 days to fully recover from
      hexamitiasis. The susceptibility of rainbow trout to IPNV remained unchanged in
      the presence of H. salmonis. Weight loss was significantly higher (P < 0.05) in
      infected than that in the parasite-free fish. Fish should be examined regularly
      for H. salmonis and treated immediately whether found to prevent economic losses
      and excessive size variation.

PMID- 24117758
TI  - Towards an advanced assessment of the hydrological vulnerability of forests to
      climate change-induced drought.

PMID- 24117761
TI  - Introduction: Aldosterone and salt: heart and kidney.

PMID- 24117760
TI  - Participatory design of an integrated information system design to support public
      health nurses and nurse managers.
AB  - OBJECTIVES: The objectives of the study were to use persona-driven and scenario
      based design methods to create a conceptual information system design to support
      public health nursing. DESIGN AND SAMPLE: We enrolled 19 participants from two
      local health departments to conduct an information needs assessment, create a
      conceptual design, and conduct a preliminary design validation. MEASURES:
      Interviews and thematic analysis were used to characterize information needs and
      solicit design recommendations from participants. Personas were constructed from
      participant background information, and scenario-based design was used to create
      a conceptual information system design. Two focus groups were conducted as a
      first iteration validation of information needs, personas, and scenarios.
      RESULTS: Eighty-nine information needs were identified. Two personas and 89
      scenarios were created. Public health nurses and nurse managers confirmed the
      accuracy of information needs, personas, scenarios, and the perceived usefulness
      of proposed features of the conceptual design. Design artifacts were modified
      based on focus group results. CONCLUSION: Persona-driven design and scenario
      based design are feasible methods to design for common work activities in
      different local health departments. Public health nurses and nurse managers
      should be engaged in the design of systems that support their work.

PMID- 24117759
TI  - Blocking the apolipoprotein E/amyloid beta interaction in triple transgenic mice
      ameliorates Alzheimer's disease related amyloid beta and tau pathology.
AB  - Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the
      major genetic risk factor for late-onset Alzheimer's disease (AD). Studies have
      shown that the binding between apoE and amyloid-beta (Abeta) peptides occurs at
      residues 244-272 of apoE and residues 12-28 of Abeta. ApoE4 has been implicated
      in promoting Abeta deposition and impairing clearance of Abeta. We hypothesized
      that blocking the apoE/Abeta interaction would serve as an effective new approach
      to AD therapy. We have previously shown that treatment with Abeta12-28P can
      reduce amyloid plaques in APP/PS1 transgenic (Tg) mice and vascular amyloid in
      TgSwDI mice with congophilic amyloid angiopathy. In the present study, we
      investigated whether the Abeta12-28P elicits a therapeutic effect on tau-related
      pathology in addition to amyloid pathology using old triple transgenic AD mice
      (3xTg, with PS1M146V , APPSwe and tauP30IL transgenes) with established pathology
      from the ages of 21 to 26 months. We show that treatment with Abeta12-28P
      substantially reduces tau pathology both immunohistochemically and biochemically,
      as well as reducing the amyloid burden and suppressing the activation of
      astrocytes and microglia. These affects correlate with a behavioral amelioration
      in the treated Tg mice.

PMID- 24117762
TI  - Community-based oral health promotion practices targeted at children and
      adolescents in Finland--developing an assessment tool.
AB  - OBJECTIVES: To develop an assessment tool for evaluating oral health promotion
      practices and to evaluate community-based oral health promotion practices
      targeted at children and adolescents with this tool. METHODS: A theoretical
      framework about health promotion planning, implementation and evaluation was made
      on the basis of a literature review. Then, information about Finnish community
      based oral health promotion practices (n=12) targeted at children and adolescents
      was collected using semi-structured interviews. Also, related documents, for
      example action plans and reports, were collected when available. Next, an
      assessment tool based on the theoretical framework was developed, and the
      recorded and transcribed interview data and other documents were evaluated with
      this tool. RESULTS: The assessment tool proved to be practical: it pointed out
      the strengths and weaknesses of the practices. The tool revealed strengths in the
      implementation and deficiencies in the planning and evaluation of oral health
      promotion practices. One-quarter of the 12 practices assessed could be considered
      'good practices'. CONCLUSIONS: There is a need to improve the planning and
      evaluation of oral health promotion practices. The assessment tool developed in
      this study might be useful for practitioners both in the field of oral health
      promotion and general health promotion.

PMID- 24117763
TI  - Risk: For Whom? Representations of Mining Activity by Different Social Actors in
      the Molango Manganese District of Hidalgo, Mexico.
AB  - Previous studies have shown high levels of manganese exposure and neurocognitive
      damage in the population living in the mining zone in Molango, Mexico. One of the
      objectives of the Intersectoral Group on Environmental Management for the mining
      district has been to provide public participation in the risk management plan. To
      achieve this, it is important to know how the different social actors represent
      the mining activity. The objectives of this study were to characterize the social
      representations of the mining activity by different social actors. A qualitative
      design was used based on in-depth interviews of residents, public officials, and
      a mining company representative. The analysis was conducted according to themes
      for each group of actors. Essentially, distinct social representations of the
      different mining activities were identified. Residents viewed mining activities
      as synonymous with contamination and, therefore, as having affected all areas of
      their environment, health, and daily life. These activities were seen as a
      collective risk. The public officials and the mining company held that there was
      no evidence of harm and saw mining activities as a generator of regional
      development. Harm to health and the environment were seen as a stance taken by
      the communities in order to obtain economic benefits from the company. These
      images of the "other" are shaped by social, political, and cultural factors. They
      make it difficult for the actors to reach cooperative agreements and thereby
      affect progress on the risk management plan. Decisionmakers need to take these
      differences into account when promoting social participation.

PMID- 24117764
TI  - Evaluation of a new German blood donor questionnaire.
AB  - BACKGROUND AND OBJECTIVES: In Germany, blood donors must complete a donor history
      questionnaire (DHQ). In 2011, a new standardized DHQ for Germany was proposed
      which included questions about sexual risk behaviour that raised concerns about
      acceptance by donors. MATERIALS AND METHODS: We assessed the acceptability and
      ease of use of the new DHQ in two German donor populations, by asking the donors
      to complete a paper survey evaluating the design and clarity of the questions of
      the new DHQ with a focus on the questions addressing sexual risk behaviour.
      RESULTS: In Greifswald, 2000 donors (mean age 32 +/- 12 years) participated, and
      in Hagen 2088 donors (mean age 48 +/- 14 years). Ratings between the two
      populations showed only minor differences. Donors reported that the questions in
      the new DHQ were understandable and clearly structured. Perception of comfort
      level with questions addressing sexual risk behaviour differed significantly
      depending on donor characteristics such as age, gender and educational level.
      Overall, the new DHQ seems to deter approximately 5% of potential donors from
      blood donation. CONCLUSION: The new DHQ was acceptable to the vast majority of
      donors. Potential donors who were older, male gender and less educated were most
      at risk of refusing to donate and may benefit from educational interventions.

PMID- 24117765
TI  - Premature infants with birth weights of 1500-1999 g exhibit considerable delays
      in several developmental areas.
AB  - AIM: To establish the prevalence and factors associated with developmental scores
      and delays in premature infants. METHODS: A cross-sectional study was conducted
      on 100 premature infants with corrected ages of 18-24 months (actual ages 19.9 +/
      2.0 months) and birth weights of 1500-1999 g. Bayley III scales were used to
      assess developmental scores, percentage of children with developmental scores
      <85, factors associated with developmental scores and delays in at least one
      developmental domain. RESULTS: The percentages and 95% confidence intervals of
      those children with developmental delays were as follows: cognitive (2.0%; 0.6
      7.0%), language (5.0%; 2.2-11.2%), motor (3.0%; 1.0-8.5%), socio-emotional
      (13.0%; 7.8-20.1%), general adaptive (26.0%; 18.4-35.4%), conceptual (17.0%; 10.9
      25.6%), social (46.0%; 36.6-55.7%) and practical (21.0%; 14.2-30.0%). Factors
      associated with delay in at least one developmental domain were as follows:
      caesarean delivery, low per capita income and peri-intraventricular haemorrhage.
      Factors associated with a reduction in developmental scores were as follows: non
      white ethnicity, lower social class, caesarean delivery, male gender, peri
      intraventricular haemorrhage, mechanical ventilation and length of
      hospitalisation. CONCLUSION: Premature infants with birth weights of 1500-1999 g
      exhibited considerable delays in several developmental areas. In addition to
      biological factors, environmental factors contributed to the reduced scores
      and/or developmental delays.

PMID- 24117766
TI  - Severity of respiratory signs and symptoms and virus profiles in Japanese
      children with acute respiratory illness.
AB  - Associations between the severity of respiratory signs and symptoms and the
      respiratory viruses identified in 214 Japanese children with acute respiratory
      illness (ARI) enrolled between January and December 2012 were studied.
      Respiratory rate, wheezing, cyanosis, and the use of accessory muscles were used
      as indices of respiratory severity and phylogenetic analysis of the viruses
      identified in these children was performed. Respiratory viruses such as
      respiratory syncytial virus (RSV), human rhinovirus (HRV), human parainfluenza
      virus (HPIV), and human metapneumovirus (HMPV) were prevalent, being detected in
      approximately 70% of the patients (151/214 patients). Co-detection of viruses
      occurred in about 9% of patients. RSV was identified more frequently in cases
      scored as moderate/severe than in those scored as mild (P < 0.05). Severity
      scores of patients with RSV were significantly higher than those of cases with
      HPIV. Moreover, severity scores in patients with mild disease and co-detections
      were higher than in those in whom only HPIV or adenovirus was detected.
      Phylogenetic analysis showed that many genotypes of HRV-A and -C with wide
      genetic divergence were associated with acute respiratory illness (ARI). On the
      other hand, only a limited number of genotypes of RSV were associated with ARI.
      HPIV and HMPV were associated with ARI at similar frequencies. These results
      suggest that different respiratory viruses with unique genetic characteristics
      can be found in patients with mild to severe ARI. 

PMID- 24117767
TI  - Bleeding-related symptoms in colorectal cancer: a 4-year nationwide population
      based study.
AB  - BACKGROUND: Little is known about the major presenting features of patients with
      colorectal cancer (CRC) in a population-based setting, especially regarding
      bleeding-related symptoms. AIM: To determine the proportion of CRC patients
      presenting with bleeding-related symptoms, to compare bleeders and nonbleeders
      and to explore the role of anticoagulants in bleeders. METHODS: This was a
      nationwide, population-based, retrospective study, investigating all patients
      diagnosed with CRC in Iceland from 2008 to 2011. Bleeding-related symptoms were
      defined as overt bleeding, iron deficiency anaemia or a positive faecal occult
      blood test. Obstructive symptoms were defined as a confirmed diagnosis of ileus
      or dilated intestines on imaging. RESULTS: Data were available for 472/496 (95%)
      patients, males 51%, mean age 69 (+/-13) years. In all, 348 (74%) patients had
      bleeding-related symptoms; of these 348 patients, 61% had overt bleeding.
      Bleeders were less likely than nonbleeders to have metastases at diagnosis, 19%
      vs. 34% (P < 0.001). Overt bleeders were less likely than nonbleeders to have
      obstructive symptoms, 2% vs. 16% respectively (P < 0.0001). Occult bleeders were
      more likely to have proximal cancer (69%) than both overt (17%) and nonbleeders
      (44%) (P < 0.0001); however, they were less likely than nonbleeders to have
      metastases (22% vs. 35%, P < 0.05). Bleeders were more likely to use warfarin
      than nonbleeders (9% vs. 3%, P < 0.05); the use of low-dose aspirin was the same
      (24%). CONCLUSIONS: The majority of patients with CRC present with bleeding
      related symptoms. Bleeders with CRC present earlier than nonbleeders. Warfarin
      use may induce bleeding in some patients, resulting in an earlier diagnosis.

PMID- 24117768
TI  - The triply troubled teenager--chronic conditions associated with fewer protective
      factors and clustered risk behaviours.
AB  - AIM: This study aimed to measure protective factors and risk behaviour among
      adolescents with chronic conditions (CCs) and to evaluate the impact of
      protective factors on risk-taking. METHODS: A population-based study of 7262
      students aged 15 and 17 years old was performed in Sormland, Sweden 2008
      (response rate 82%). The questionnaire explored background factors, CCs, risk
      behaviours and protective factors. CCs were reported by 8%, while 58% had no
      health problems. RESULTS: Girls with CCs encompassed less individual protective
      factors, while boys with CCs tended to over-report all individual risk behaviours
      compared with healthy peers. Both boys and girls with CCs were more likely to
      report few protective factors and co-occurrence of risk behaviours. The adjOR for
      clustered health risk behaviours was 1.6 (1.0-2.5) in youths with CCs and >=4
      protective factors and 6.3 (3.6-10.9) in youths with CCs and 0-3 protective
      factors, as compared to healthy peers with >=4 protective factors. CONCLUSION:
      Adolescents with CCs reported fewer protective factors and more risk behaviours
      than their healthy peers. The vulnerability of adolescents with CCs and few
      protective factors is important to acknowledge. Professionals should provide
      stronger protection for these adolescents, to prevent risky behaviour.

PMID- 24117769
TI  - Multinucleate cell angiohistiocytoma with hypertrophic nerves.
AB  - Multinucleate cell angiohistiocytoma (MCAH) represents a rare benign skin lesion
      characterized by multiple papules that are usually found on the distal
      extremities or face of middle-aged women. We report on a 60-year-old male with a
      history of monoclonal gammopathy and severe rheumatoid arthritis who had several
      asymptomatic red-to-livid papules grouped on the right side of his trunk. The
      lesions had been present for a few years and were gradually enlarging. Biopsies
      from three lesions showed a spectrum of changes consisting of a proliferation of
      small venules together with thickened collagen bundles and increased numbers of
      interstitial cells including bizarre, multinucleated giant cells.
      Immunohistochemically, the multinucleated cells were positive for vimentin and
      lysozyme while the interstitial cells expressed CD68, factor XIIIa and lysozyme.
      Interestingly, strikingly enlarged dermal nerves were seen in all the three
      biopsies and two of the biopsies showed an accompanying infiltrate of lymphocytes
      and plasma cells. 

PMID- 24117770
TI  - The epidemiology of anaphylaxis in Europe: a systematic review.
AB  - BACKGROUND: Anaphylaxis is an acute, potentially fatal, multi-organ system,
      allergic reaction caused by the release of chemical mediators from mast cells and
      basophils. Uncertainty exists around epidemiological measures of incidence and
      prevalence, risk factors, risk of recurrence, and death due to anaphylaxis. This
      systematic review aimed to (1) understand and describe the epidemiology of
      anaphylaxis and (2) describe how these characteristics vary by person, place, and
      time. METHODS: Using a highly sensitive search strategy, we identified systematic
      reviews of epidemiological studies, descriptive and analytical epidemiological
      investigations, and studies involving analysis of routine data. RESULTS: Our
      searches identified a total of 5,843 potentially eligible studies, of which 49
      satisfied our inclusion criteria. Of these, three were suitable for pooled
      estimates of prevalence. The incidence rates for all-cause anaphylaxis ranged
      from 1.5 to 7.9 per 100,000 person-years. These data indicated that an estimated
      0.3% (95% CI 0.1-0.5) of the population experience anaphylaxis at some point in
      their lives. Food, drugs, stinging insects, and latex were the most commonly
      identified triggers. CONCLUSIONS: Anaphylaxis is a common problem, affecting an
      estimated 1 in 300 of the European population at some time in their lives. Future
      research needs to focus on better understanding of the trends across Europe and
      identifying those most likely to experience fatal reactions.

PMID- 24117771
TI  - Diversity of cultivable beta-glycosidase-producing micro-organisms isolated from
      the soil of a ginseng field and their ginsenosides-hydrolysing activity.
AB  - This research aimed to explore the diversity of cultivable beta-glycosidase
      producing micro-organisms in ginseng field soil. Fifty-three strains showing beta
      glucosidase activity were isolated from a ginseng field, using a newly designed
      Esculin-R2A agar. All the isolated strains belonged to the genus Agrobacterium,
      Arthrobacter, Burkholderia, Dyella, Edaphobacter, Luteibacter, Mucilaginibacter,
      Paenibacillus, Phenylobacterium, Pseudomonas, Sphingomonas and Streptomyces. The
      main beta-glucosidase-producing micro-organisms in the ginseng field soil were
      Sphingomonas, Burkholderia, Luteibacter and Streptomyces, while concentrations of
      Agrobacterium, Arthrobacter, Paenibacillus and Pseudomonas were relatively low.
      Of these micro-organisms, the strain GS 09 could hydrolyse major ginsenosides
      Rb1, Rb2 and Rc to the active metabolite compound K. The strain GS 09 belonged to
      the genus Sphingomonas, and its 16S rRNA gene sequence showed 100% similarities
      with that of Sphingomonas asaccharolytica. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first study to provide information of cultivable beta-glycosidase
      producing micro-organisms in ginseng field soil. The strain GS 09 has potential
      to be applied on the preparation for minor ginsenoside C-K in pharmaceutical
      industry.

PMID- 24117773
TI  - Recommendation to include formaldehyde 2.0% aqua in the European baseline patch
      test series.
AB  - BACKGROUND: The currently used patch test concentration of formaldehyde (1.0%
      aqua; 0.30 mg/cm(2)) has been shown to fail to detect ~ 50% of contact allergies
      to formaldehyde. OBJECTIVES: To justify the inclusion of formaldehyde 2.0% aqua
      (0.60 mg/cm(2)) in the European baseline patch test series. METHODS: A survey of
      the reported frequencies of contact allergy to formaldehyde found with
      formaldehyde 2.0% aqua as compared with 1.0% aqua was performed. Studies that
      describe a standardized patch test technique for obtaining a correct dose per
      unit area were included. Experimental provocation tests in patients with contact
      allergy to formaldehyde detected only with 2.0% aqua were also surveyed. RESULTS:
      In a multicentre study performed in 12 dermatology clinics among 3591
      individuals, 3.4% reacted to 2.0%, and 1.8% reacted to 1.0% (p < 0.001). A
      randomized double-blind repeated open application test performed in individuals
      reacting only to 2.0% but not to 1.0% showed that 9 of 17 formaldehyde-allergic
      individuals reacted to a moisturizer that contained formaldehyde (p < 0.001).
      CONCLUSIONS: It is recommended that formaldehyde 2.0% aqua (0.60 mg/cm(2)) should
      replace formaldehyde 1.0% in the European baseline series from 2014. With the
      Finn Chamber((r)) technique, a standardized amount of 15 ul of the solution
      obtained by using a micropipette should be used.

PMID- 24117772
TI  - Fresh-frozen plasma transfusion did not reduce 30-day mortality in patients
      undergoing cardiopulmonary bypass cardiac surgery with excessive bleeding: the
      PLASMACARD multicenter cohort study.
AB  - BACKGROUND: During on-pump cardiac surgery, hemorrhagic complications occur
      frequently. Fresh-frozen plasma (FFP) is widely transfused to provide coagulation
      factors. Yet, no randomized clinical trial has demonstrated its benefits on
      mortality. We assessed the relationship between therapeutic transfusion of FFP
      and 30-day mortality in cardiac surgery patients suffering from excessive
      bleeding in a prospective cohort study. STUDY DESIGN AND METHODS: Adult patients
      who underwent on-pump cardiac surgery and experienced excessive bleeding during
      the 48-hour perioperative period were recruited from 15 French centers between
      February 2004 and January 2006. Patients who received a preventive FFP
      transfusion were excluded. The association between FFP transfusion and all cause
      30-day mortality was estimated using a Cox proportional hazards model, adjusted
      for confounding. A propensity score (PS) sensitivity analysis was also performed.
      RESULTS: Among 967 patients included in this study, 58.1% received FFP. The
      median dose was 11.3 mL/kg (interquartile range, 7.6-19.5). The cumulative 30-day
      mortality rate was 11.3% (95% confidence interval [CI], 9.5-13.5). FFP
      transfusion was associated with a higher 30-day mortality (hazard ratio [HR],
      3.2; 95% CI, 1.7-6.1) in univariate analysis; however, after adjusting for
      prognostic factors, there was no longer any association (HR, 1.5; 95% CI, 0.8
      3.0, p = 0.20). The results of the PS analysis were consistent with the adjusted
      analysis. CONCLUSION: Among on-pump cardiac surgery patients experiencing
      excessive perioperative bleeding, there is no evidence of a beneficial impact of
      FFP transfusion on mortality.

PMID- 24117774
TI  - Decorin and biglycan immunolocalization in non-villous structures of healthy and
      pathological human placentas.
AB  - AIMS: Decorin and biglycan are members of the small leucine-rich proteoglycan
      family, and constituents of both the extracellular matrix (ECM) and the cell
      surface. They are recognized as important factors in the control of
      proliferation, migration and invasion in vivo and in vitro. In this study, the
      localization patterns of decorin and biglycan were determined in healthy
      placentas and in highly invasive placental pathologies. METHODS AND RESULTS: The
      study included immunolocalization of decorin and biglycan in samples of first
      trimester and term placentas, placenta accreta, invasive mole, and
      choriocarcinoma. Extravillous cytotrophoblast (EVT) cells were positive for both
      proteoglycans in all pathologies and in first-trimester placentas, although not
      in term placentas. Biglycan was immunolocalized in the ECM of all healthy and
      pathological placentas, whereas decorin was observed only in term placenta ECM.
      CONCLUSIONS: The expression of both proteoglycans was cell-specific and gestation
      time-dependent in healthy placentas, and was associated with invasive EVT cells
      in pathological placentas. In view of the biological properties of these
      molecules, it is possible that the biglycan pattern found here is intrinsically
      implicated in the invasive activity of EVT cells in both healthy and disordered
      placentas.

PMID- 24117775
TI  - Not by labor alone: considerations for value influence use of the labor rule in
      ownership transfers.
AB  - People often assign ownership to the person who has invested labor into making an
      object (labor rule). However, labor usually improves objects and increases their
      value, and it has not been investigated whether these considerations underlie
      people's use of the labor rule. We presented participants with third-party
      ownership conflicts between an owner of materials and an artist who used the
      materials for some artwork. Experiment 1 revealed that participants were more
      likely to transfer ownership to the artist for low-value materials than for high
      value materials, and Experiment 2 showed that this effect was further moderated
      by the amount of effort the artist had invested. A third experiment confirmed
      that participants transferred ownership more often if the artist's labor had
      increased the value of the materials than when it had added no value. These
      findings suggest that considerations for value underlie ownership transfers
      following the investment of labor. 

PMID- 24117776
TI  - Seasonal dynamics of free-living tintinnid ciliate communities revealed by
      environmental sequences from the North-West Mediterranean Sea.
AB  - The species-rich order Tintinnida is a group of planktonic ciliates ubiquitous in
      coastal marine waters, which can be well described using molecular estimates of
      diversity. We studied temporal changes of tintinnid diversity over 1 year in a
      coastal Mediterranean Sea location (Villefranche-sur-Mer, France) at five
      different depths (5, 25, 50, 100, and 160 m) and one additional year at 50 m
      depth by combining denaturing gel gradient electrophoresis (DGGE) community
      fingerprinting with direct PCR amplification, cloning and sequencing of small
      subunit (SSU), 5.8S, and large-subunit (LSU) rRNA genes together with the
      corresponding internal transcribed spacers (ITS). We amplified tintinnid
      sequences in all samples. All identified phylotypes were closely related to
      described species, showing that there is a good phylogenetic reference sequence
      data set allowing accurate estimation of tintinnid diversity in these waters.
      Tintinnid community composition exhibited marked seasonal changes. Surprisingly,
      the tintinnid SSU rDNA-based species composition did not show any clear
      relationship to measured environmental parameters (temperature, salinity, light,
      phytoplankton biomass). Nonetheless, the comparison of tintinnid community
      composition using UniFrac revealed three significant clusters of sequences
      grouping, respectively, samples collected in winter, autumn, and summer, leading
      to the hypothesis that seasonal effects on tintinnid community composition might
      be related to biotic parameters. In addition, phylogenetic trees based on the
      concatenated SSU + LSU rDNA and ITS sequences showed a better resolution than SSU
      rDNA alone to discriminate closely related species. 

PMID- 24117777
TI  - Cystic partially regressed clear cell renal cell carcinoma: a potential mimic of
      multilocular cystic renal cell carcinoma.
AB  - AIMS: To study clear cell renal cell carcinomas with predominant cystic and
      sclerotic components, in which a solid epithelial component precluded a diagnosis
      of multilocular cystic renal cell carcinoma. We designated these tumours 'cystic
      partially regressed clear cell renal cell carcinoma.' METHODS AND RESULTS: Twenty
      seven tumours were studied, from patients with a median age of 58 years; the
      stage was most often pT1 (89%). The Fuhrman grade was 2 (48%), 1 (33%), or 3
      (19%). The solid epithelial component constituted up to 30% of the tumour volume
      (median, 10%), whereas the cystic component constituted 15-80% (median, 65%), and
      the sclerotic component 10-70% (median, 20%). Thin fibrovascular septa lined by
      cells with clear cytoplasm were almost always present, resembling multilocular
      cystic renal cell carcinoma. Both zones of sclerosis and fibrovascular septa
      often contained inconspicuous epithelial cells. Sclerotic areas ranged in
      appearance from a cellular fibroblastic reaction to scar-like with a residual
      network of capillaries resembling haemangioma. No patient developed recurrence or
      metastasis. CONCLUSIONS: Cystic partially regressed clear cell renal cell
      carcinoma is an uncommon pattern of clear cell renal cell carcinoma, being
      composed of cysts with solid epithelial and sclerotic components that
      differentiate it from multilocular cystic renal cell carcinoma.

PMID- 24117778
TI  - Associations between obesity and physical activity in dogs: a preliminary
      investigation.
AB  - OBJECTIVES: To assess whether obesity has any association with objectively
      measured physical activity levels in dogs. METHODS: Thirty-nine dogs wore
      Actigraph GT3X accelerometers (Actigraph) for 7 consecutive days. Each dog was
      classified as ideal weight, overweight or obese using the 5-point body condition
      scoring system. Total volume of physical activity and time spent in sedentary
      behaviour, light-moderate intensity physical activity and vigorous intensity
      physical activity were compared between body condition categories. RESULTS: Valid
      accelerometry data were returned for 35 of 39 dogs recruited. Eighteen dogs were
      classed as ideal weight, 9 as overweight and the remaining 8 as obese. All dogs
      spent a significant proportion of the day sedentary and obese dogs spent
      significantly less time in vigorous intensity physical activity than ideal weight
      dogs (7 +/-3 minute/day versus 21 +/-15 minute/day, P=0.01). CLINICAL
      SIGNIFICANCE: Obesity is associated with lower vigorous intensity physical
      activity in dogs, as is also thought to occur in humans. These preliminary
      findings will help inform a future, larger study and may also improve our
      understanding of the associations between obesity and physical activity in dogs.

PMID- 24117779
TI  - Blood eosinophil counts during bronchiolitis are related to bronchial hyper
      responsiveness and lung function in early adolescence.
AB  - AIM: To assess whether inflammatory markers measured in urine and blood during
      acute bronchiolitis in infancy were associated with asthma, lung function,
      bronchial hyper-responsiveness (BHR) and atopy at 11 years of age. METHODS: We
      included 105 children hospitalised for bronchiolitis during their first year of
      life. At hospitalisation, urinary (U-) eosinophil protein X, U-leukotriene E4 , U
      prostaglandin 9alpha, 11beta-PGF2 and blood eosinophil counts were measured.
      Ninety-five children (90%) were available for follow-up at 11 years of age.
      RESULTS: At follow-up, higher blood eosinophil counts obtained during
      bronchiolitis were observed in the group with asthma than in the group without
      asthma (median 0.27 versus 0.09 * 10(9) /L, respectively, p = 0.048). By
      regression analyses, blood eosinophil counts during the acute bronchiolitis were
      positively associated with BHR (p = 0.006) and negatively associated with forced
      expiratory volume in first second (p = 0.025) at 11 years of age. None of the
      other inflammatory markers were associated with asthma, lung function, BHR or
      atopy at 11 years of age. CONCLUSION: Eosinophil inflammation during
      bronchiolitis may have a long-term impact on lung function and airway
      responsiveness. The associations could be related to virus-host interactions
      during bronchiolitis or to predisposed children.

PMID- 24117781
TI  - In vitro anti-Malassezia activity and potential use in anti-dandruff formulation
      of Asparagus racemosus.
AB  - OBJECTIVE: Malassezia species are frequently associated with dandruff and
      seborrhoeic dermatitis. The study was conducted to evaluate anti-fungal
      activities of the extracts obtained from the roots of Asparagus racemosus Willd
      against Malassezia furfur and M. globosa. METHODS: Asparagus racemosus roots were
      successively extracted with the series of solvents, that is, hexane, ethanol and
      water, and also a saponin-enriched fraction was prepared. The amounts of saponin
      (equivalent to shatavarin IV) in the extracts were determined using ELISA. The
      extracts were tested for anti-fungal activity by disc diffusion and broth
      microdilution methods. RESULTS: By disc diffusion, only the ethanolic and saponin
      enriched extracts demonstrated anti-fungal activity against M. furfur and M.
      globosa at the concentration of 1 mg per disc whereas the extracts with other
      solvents were ineffective. Multiple concentrations using the broth microdilution
      method against M. furfur and M. globosa yielded minimum inhibitory concentrations
      (MICs) of 25 mg mL(-1) for the ethanolic extract but much higher potency for the
      saponin-enriched extract: MICs to 0.20 and 0.40 mg mL(-1) for M. furfur and M.
      globosa, respectively. These extracts showed no antagonist effect with the anti
      fungal agents, ketoconazole and zinc pyrithione. CONCLUSION: These studies
      revealed the antifungal activity of A. racemosus roots extracts. Because A.
      racemosus is also anti-inflammatory agent, it has the potential use as an active
      ingredient in an anti-dandruff formulation.

PMID- 24117780
TI  - Electrophysiologic characteristics and pharmacologic response of human
      cardiomyocytes isolated from a patient with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common monogenic
      cardiac disorder encountered in the clinic. Data relative to the
      electrophysiologic characteristics and pharmacologic responsiveness of human
      tissues and cells isolated from patients with HCM are rare. As a consequence,
      cellular mechanisms underlying arrhythmogenicity are poorly understood. METHODS:
      Cardiomyocytes were enzymatically dissociated from a septal myectomy surgically
      removed from a patient with obstructive HCM. Sharp microelectrodes and patch
      clamp techniques were used to evaluate action potential and sodium channel
      current (INa ) characteristics. RESULTS: Action potential morphology recorded was
      typical of an M cell, but with a longer than normal duration (APD) and a
      relatively steep APD-rate relationship. APD at all rates was significantly
      reduced following exposure to ranolazine (10 MUM). Whole cell patch-clamp
      recording yielded robust peak INa and large late INa (1.1% of peak INa vs 0.1
      0.2% in healthy controls). A large window current was observed as well.
      Ranolazine (10 MUM) shifted steady-state V0.5 of inactivation by -8 mV, reduced
      late INa by 82%, and significantly diminished the window current. CONCLUSION: Our
      results indicate the presence of cells with M-cell characteristics in the septum
      of the human heart, as has previously been described in the canine heart. They
      also point to an ameliorative effect of ranolazine to reduce augmented late INa
      and thus to reduce the prolonged APD in the setting of HCM. These results suggest
      a potential therapeutic role for ranolazine in HCM.

PMID- 24117782
TI  - Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting
      oxidative stress, extracellular matrix protein accumulation and cytokine
      production.
AB  - 1. Liver fibrosis is characterized by excessive accumulation of extracellular
      matrix (ECM) proteins in the liver. Probucol, a lipid-lowering drug, was found to
      prevent liver injury in rats treated with carbon tetrachloride (CCl4 ). In the
      present study, we investigated whether probucol has protective effect against
      liver fibrosis in rats treated with ethanol and CCl4 . 2. Thirty rats were
      randomly divided into five groups. Groups I and II served as the normal control
      and the model of liver fibrosis, respectively. Groups III-V were treated with
      probucol at a doses of 250, 500 and 1000 mg/kg, respectively. Rats in Group II
      were fed a complex diet that includes alcohol, corn oil and pyrazole, and were
      injected intraperitoneally with CCl4 to induce hepatic fibrosis. Blood was
      obtained to assess markers of liver function. Liver samples were collected to
      evaluate mRNA and protein expression, histological changes and oxidative stress.
      3. Probucol significantly attenuated the histological changes induced by ethanol
      + CCl4 and improved liver function. Expression levels of alpha-smooth muscle
      actin and collagen I was decreased in the probucol-treated groups. Moreover,
      probucol markedly suppressed increases in oxidative stress, ECM protein
      accumulation and cytokine production induced by ethanol + CCl4 . Finally,
      probucol inhibited activation of the extracellular signal-regulated kinase
      signalling pathway induced by ethanol + CCl4 . 4. Our findings reveal that
      probucol attenuates ethanol + CCl4 -induced liver fibrosis by inhibiting
      oxidative stress, ECM protein accumulation and cytokine production. These data
      suggest that probucol may be useful for the prevention and treatment of hepatic
      fibrosis.

PMID- 24117783
TI  - Characteristics of traditional Chinese medicine use in children with asthma: a
      nationwide population-based study.
AB  - Asthma is a chronic inflammatory airway disease accounting for severe morbidity
      and mortality in children. To determine the characteristics of traditional
      Chinese medicine (TCM) used to treat pediatric asthma, we conducted a nationwide
      population-based study by analyzing a cohort of one million randomly sampled
      patients from the beneficiaries of the National Health Insurance Program in
      Taiwan from 2002 to 2010. Children under 18 years of age with newly diagnosed
      asthma (ICD-9-CM code: 493, N = 45 833) were enrolled, and 57.95% (N = 26 585) of
      them had used TCM. The number of TCM users was significantly more than that of
      non-TCM users in school-age children. The most commonly prescribed TCM formula is
      Ding-chuan-tang, or Xing-ren (Semen Armeniacae Amarum) for the single herb. Our
      study is the first to reveal characteristics and prescription patterns of the use
      of TCM in children with asthma. Further research is needed to elucidate the
      efficacy and safety of these Chinese herbal products.

PMID- 24117784
TI  - A psychophysical technique for estimating the accuracy and precision of
      retinoscopy.
AB  - BACKGROUND: The accuracy and precision of retinoscopy need to be evaluated in an
      objective and unambiguous manner to judge an individual's performance in this
      task during training or in research for consistent measurements of refractive
      error. This study describes and evaluates a psychophysical technique for
      obtaining simultaneous and unbiased estimates of accuracy and precision in
      retinoscopy. METHODS: Subjects with zero to 12 years of experience with
      retinoscopy performed the psychophysical task on a model eye (75 subjects) and on
      a cyclopleged human eye with spherical refractive error (30 subjects). Subjects
      made forced choice judgments of 'with' or 'against' for lens powers within +/-
      0.5 D of expected neutrality (in 0.12 D steps), each placed 20 times before the
      eye in random order. Accuracy and precision were determined from the mean and
      standard deviation of the resultant psychometric function. RESULTS: Subjects
      could be qualitatively divided into those with good and poor accuracy and
      precision based on the task outcomes. The median and inter-quartile range of
      accuracy (no experience: 0.16 +/- 0.34 D; four or more years of experience: 0.06
      +/- 0.11 D) and precision (no experience: 0.30 +/- 0.39 D; four or more years of
      experience group: 0.13 +/- 0.08 D) improved with task experience (p < 0.001).
      Median accuracy and precision in the human eye were similar to the model eye (p >
      0.8). Accuracy and precision were poorly correlated with each other for both the
      human eye and model eye (|rho| <= 0.20; p >= 0.09 for all). CONCLUSION: The
      psychophysical retinoscopic task could differentiate subjects based on their
      accuracy and precision and also capture key elements of improvement in
      retinoscopic performance with experience. Retinoscopic performance using this
      task was similar to previous reports using routine clinical retinoscopy.
      Therefore, the psychophysical technique may be used to evaluate and monitor
      objectively retinoscopic performance.

PMID- 24117785
TI  - Spikar, a novel drebrin-binding protein, regulates the formation and
      stabilization of dendritic spines.
AB  - Dendritic spines are small, actin-rich protrusions on dendrites, the development
      of which is fundamental for the formation of neural circuits. The actin
      cytoskeleton is central to dendritic spine morphogenesis. Drebrin is an actin
      binding protein that is thought to initiate spine formation through a unique
      drebrin-actin complex at postsynaptic sites. However drebrin overexpression in
      neurons does not increase the final density of dendritic spines. In this study,
      we have identified and characterized a novel drebrin-binding protein, spikar.
      Spikar is localized in cell nuclei and dendritic spines, and accumulation of
      spikar in dendritic spines directly correlates with spine density. A reporter
      gene assay demonstrated that spikar acts as a transcriptional co-activator for
      nuclear receptors. We found that dendritic spine, but not nuclear, localization
      of spikar requires drebrin. RNA-interference knockdown and overexpression
      experiments demonstrated that extranuclear spikar regulates dendritic spine
      density by modulating de novo spine formation and retraction of existing spines.
      Unlike drebrin, spikar does not affect either the morphology or function of
      dendritic spines. These findings indicate that drebrin-mediated postsynaptic
      accumulation of spikar regulates spine density, but is not involved in regulation
      of spine morphology.

PMID- 24117786
TI  - The effect of extracorporeal membrane oxygenation therapy on systemic oxidative
      stress injury in a porcine model.
AB  - Extracorporeal membrane oxygenation (ECMO) therapy can result in systemic immune
      inflammation and trigger a hemolytic response, both of which can lead to
      oxidative stress injury. However, currently, there are few studies about whether
      ECMO can lead to oxidative stress injury. The objective of this study was to
      determine the effect of ECMO therapy on systemic oxidative stress. Twelve pigs
      were randomly divided into control and ECMO treatment groups. Blood samples were
      collected at -1, 0, 2, 6, 12, and 24 h during ECMO therapy in order to measure
      the levels of various oxidative stress markers in plasma. All animals included in
      the study were euthanized after 24 h of ECMO treatment. Malondialdehyde (MDA) was
      used as a marker of oxidation, and superoxide dismutase (SOD), glutathione (GSH),
      and total antioxidant capacity (T-AOC) were used as indices for antioxidant
      activity. The plasma levels of each molecule were similar when measured at -1 and
      0 h (P > 0.05). In the control group, MDA, SOD, GSH, and T-AOC remained
      relatively constant throughout the study period. However, when ECMO was
      administered for 2 h, plasma levels of MDA increased significantly; conversely,
      levels of SOD, GSH, and T-AOC decreased. Maximum MDA levels and minimal SOD, GSH,
      and T-AOC levels were observed after 6 h of ECMO treatment. MDA and SOD levels
      had returned to baseline at 24 h. At this time-point, levels of MDA and T-AOC in
      samples from the right frontal cortex and jejunum differed significantly between
      the control and ECMO treatment groups. These results show that early ECMO
      treatment can induce significant oxidative stress injury in plasma. However, in
      the latter stage of the treatment, the oxidative stress injury can be repaired
      gradually. ECMO treatment can also result in mild oxidative stress injury in the
      jejunum and brain tissue. 

PMID- 24117787
TI  - A new type of lordosis and vertebral body compression in Gilthead sea bream,
      Sparus aurata L.: aetiology, anatomy and consequences for survival.
AB  - A new type of vertebral malformation is described, consisting of deformed
      cartilaginous neural and haemal processes and the compression and fusion of
      vertebral bodies. The malformation is designated as haemal vertebral compression
      and fusion (haemal VCF). We studied the aetiology of the malformations and
      described microanatomical histopathological alterations. The malformations were
      detected during routine quality control in one of six monitored Gilthead sea
      bream populations. Haemal VCF affected the posterior part of the vertebral column
      (haemal vertebrae). In 20% of the deformed specimens, haemal VCF was combined
      with lordosis. At 35 dph (days post-hatching), early anatomical signs of the
      haemal VCF consisted of abnormal centrum mineralization, malformed cartilaginous
      neural and haemal processes and developing lordotic alterations. The histological
      examination of the deformed individuals revealed that haemal VCF is preceded by
      notochord abnormalities. The frequency of deformed individuals was three times
      higher at 35 than at 61 dph (50.3% vs. 17.2%, n = 157 and n = 250, respectively).
      No signs of repair or reversion of malformations have been observed. Thus, the
      steep decrease in deformities in older animals suggests that haemal VCF is linked
      to high mortality rates. The results are discussed in respect of the possible
      causative factors of haemal VCF.

PMID- 24117789
TI  - "Not in (or under) my backyard": Geographic proximity and public acceptance of
      carbon capture and storage facilities.
AB  - Carbon capture and storage (CCS) is an innovative technical approach to mitigate
      the problem of climate change by capturing carbon dioxide emissions and injecting
      them underground for permanent geological storage. CCS has been perceived both
      positively, as an innovative approach to facilitate a more environmentally benign
      use of fossil fuels while also generating local economic benefits, and
      negatively, as a technology that prolongs the use of carbon-intensive energy
      sources and burdens local communities with prohibitive costs and ecological and
      human health risks. This article extends existing research on the "not in my
      backyard" (NIMBY) phenomenon in a direction that explores the public acceptance
      of CCS. We utilize survey data collected from 1,001 residents of the coal
      intensive U.S. state of Indiana. Over 80% of respondents express support for the
      general use of CCS technology. However, 20% of these initial supporters exhibit a
      NIMBY-like reaction and switch to opposition as a CCS facility is proposed close
      to their communities. Respondents' worldviews, their beliefs about the local
      economic benefits that CCS will generate, and their concerns about its safety
      have the greatest impact on increasing or decreasing the acceptance of nearby
      facilities. These results lend valuable insights into the perceived risks
      associated with CCS technology and the possibilities for its public acceptance at
      both a national and local scale. They may be extended further to provide initial
      insights into likely public reactions to other technologies that share a similar
      underground dimension, such as hydraulic fracturing. 

PMID- 24117788
TI  - A comparison of the cornerstones of public health nursing in Norway and in the
      United States.
AB  - OBJECTIVES: This study describes a comparison of the values and beliefs
      foundational to community nursing practice in Norway with the Cornerstones of
      Public Health Nursing based on public health nursing practice in the United
      States. DESIGN AND SAMPLE: Methods included a review of the literature and focus
      groups to determine primary beliefs and values foundational to nursing practice
      in family, school, and home care settings in Norway. MEASURES: Authors reviewed
      documents written in English and Norwegian for content on values and beliefs
      represented in public health nursing. Data were gathered from two focus group
      meetings each with school, home care, and family health nurses in Norway (n = 19;
      n = 11). METHOD: Focus group questions addressed aspects of the values and
      beliefs of public health that are foundational to public health nursing. The
      researchers synthesized content themes of literature and focus groups. RESULTS:
      Nine Norwegian cornerstones emerged from literature and focus groups. Six of the
      cornerstones were the same as the cornerstones from the United States, two were
      modified, and one new cornerstone emerged from the data. CONCLUSIONS: The values
      and beliefs represented in the different modified cornerstones based on Norwegian
      community nursing practice capture the essence of public health nursing in
      Norway. The similarities between the two countries show that nurses have much in
      common, despite different health and governmental systems and laws.

PMID- 24117790
TI  - Dietary reference intakes: cases of appropriate and inappropriate uses.
AB  - The dietary reference intakes (DRIs) are a set of reference intake levels for
      nutrients that can be used for planning diets and assessing nutrient inadequacies
      of individuals and groups. Since the publication of the DRI reports 1997-2004,
      the reference intake levels have been used for various purposes. While DRIs have
      been used appropriately for planning and assessing diets for many different
      situations, there have been instances in which specific DRI categories have not
      been applied as intended. In this review, cases are described in which DRIs were
      applied correctly, as well as cases from the growing number of examples in which
      the wrong DRI was used or DRIs were used incorrectly. 

PMID- 24117791
TI  - Principles for building public-private partnerships to benefit food safety,
      nutrition, and health research.
AB  - The present article articulates principles for effective public-private
      partnerships (PPPs) in scientific research. Recognizing that PPPs represent one
      approach for creating research collaborations and that there are other methods
      outside the scope of this article, PPPs can be useful in leveraging diverse
      expertise among government, academic, and industry researchers to address public
      health needs and questions concerned with nutrition, health, food science, and
      food and ingredient safety. A three-step process was used to identify the
      principles proposed herein: step 1) review of existing PPP guidelines, both in
      the peer-reviewed literature and at 16 disparate non-industry organizations; step
      2) analysis of relevant successful or promising PPPs; and step 3) formal
      background interviews of 27 experienced, senior-level individuals from academia,
      government, industry, foundations, and non-governmental organizations. This
      process resulted in the articulation of 12 potential principles for establishing
      and managing successful research PPPs. The review of existing guidelines showed
      that guidelines for research partnerships currently reside largely within
      institutions rather than in the peer-reviewed literature. This article aims to
      introduce these principles into the literature to serve as a framework for
      dialogue and for future PPPs. 

PMID- 24117792
TI  - Long-chain omega-3 fatty acids: time to establish a dietary reference intake.
AB  - The beneficial effects of consuming omega-3 polyunsaturated fatty acids (n-3
      PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      on cardiovascular health have been studied extensively. To date, there is no
      dietary reference intake (DRI) for EPA and DHA, although many international
      authorities and expert groups have issued dietary recommendations for them. Given
      the substantial new evidence published since the last Institute of Medicine (IOM)
      report on energy and macronutrients, released in 2002, there is a pressing need
      to establish a DRI for EPA and DHA. In order to set a DRI, however, more
      information is needed to define the intakes of EPA and DHA required to reduce the
      burden of chronic disease. Information about potential gender- or race-based
      differences in requirements is also needed. Given the many health benefits of EPA
      and DHA that have been described since the 2002 IOM report, there is now a strong
      justification for establishing a DRI for these fatty acids. 

PMID- 24117793
TI  - Residual aggregates in platelet products: what do we know?
AB  - BACKGROUND AND OBJECTIVES: Platelet (PLT) aggregates can occur during or after
      PLT component processing. However, very few reports investigating the phenomenon
      and its clinical significance have been published. In this review, currently
      available information about aggregates in PLT products is summarized and possible
      causal factors as well as preventive strategies are discussed. MATERIALS AND
      METHODS: A review of the MEDLINE(r) database for relevant publications from 1960
      to May 2013 was conducted. RESULTS: It is well known that PLT aggregates may
      occur during or after the PLT product preparation process. These aggregates
      normally dissipate with rest and agitation. However, in some rare cases, the
      aggregates do not dissipate within 24 h and can persist up to the end of storage.
      Exposure to low temperature, low pH, short resting period after collection,
      different collection systems, presence of bubbles or foam inside the PLT bag, PLT
      container interactions, proper product mixing and donor-dependent variables may
      have an impact on the formation of PLT aggregates. Although publications are
      rare, the presence of small numbers of PLT aggregates appears to have only
      limited impact on PLT in vitro quality. Furthermore, data on the clinical impact
      of PLT aggregates are lacking. CONCLUSION: Despite the fact that PLT aggregates
      occur in PLT products, published data on this topic remain scant. Considering the
      concern of clinicians about this phenomenon, more studies are needed which should
      focus on the possible clinical impact of such aggregates and precautions to avoid
      PLT aggregate formation in PLT products.

PMID- 24117794
TI  - Myricetin suppresses lipoteichoic acid-induced interleukin-1beta and
      cyclooxygenase-2 expression in human gingival fibroblasts.
AB  - Periodontitis is an inflammatory disease affecting the connective tissue and
      supporting bone surrounding the teeth. In periodontitis, human gingival
      fibroblasts (HGFs) synthesize IL-1beta, causing a progressive inflammatory
      response. Flavones demonstrate a variety of biological activity: among others,
      they possess anti-inflammatory properties. Myricetin is a flavone with a strong
      anti-inflammatory activity. The objective of this study was to evaluate the
      effect of the flavonoid myricetin on HGFs under inflammatory conditions induced
      by lipoteichoic acid (LTA). the effect of myricetin on HGFs was assessed by
      measuring cell viability, signaling pathways and IL-1beta expression and
      synthesis. It was found that, over time, myricetin did not affect cell viability.
      However, it inhibited activation of p38 and extracellular-signal-regulated kinase
      1/2 in LTA-treated HGFs and also blocked IkappaB degradation and cyclooxygenase-2
      and prostaglandin E2 synthesis and expression. These findings suggest that
      myricetin has therapeutic effects in the form of controlling LTA-induced
      inflammatory responses. 

PMID- 24117795
TI  - Inhibition of matrix metalloproteinase-9 and nuclear factor kappa B contribute to
      melatonin prevention of motility and invasiveness in HepG2 liver cancer cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide
      because of its high incidence and its metastatic potential. Extracellular matrix
      degradation by matrix metalloproteinases (MMPs) has been connected with cancer
      cell invasion, and it has been suggested that inhibition of MMPs by synthetic and
      natural inhibitors may be of great importance in the HCC therapies. Melatonin,
      the main product of the pineal gland, exerts antiproliferative, proapoptotic, and
      antiangiogenic properties in HepG2 human hepatocellular cells, and exhibits anti
      invasive and antimetastatic activities by suppressing the enzymatic activity of
      MMP-9 in different tumor types. However, the underlying mechanism of anti
      invasive activity in HCC models has not been fully elucidated. Here, we
      demonstrate that 1 mm melatonin dosage reduced in IL-1beta-induced HepG2 cells
      MMP-9 gelatinase activity and inhibited cell invasion and motility through
      downregulation of MMP-9 gene expression and upregulation of the MMP-9-specific
      inhibitor tissue inhibitor of metalloproteinases (TIMP)-1. No significant changes
      were observed in the expression and activity of MMP-2, the other proteinase
      implicated in matrix collagen degradation, and its tissue inhibitor, TIMP-2.
      Also, melatonin significantly suppressed IL-1beta-induced nuclear factor-kappaB
      (NF-kappaB) translocation and transcriptional activity. In summary, we
      demonstrate that melatonin modulates motility and invasiveness of HepG2 cell in
      vitro through a molecular mechanism that involves TIMP-1 upregulation and
      attenuation of MMP-9 expression and activity via NF-kappaB signal pathway
      inhibition.

PMID- 24117796
TI  - The relationship between body growth and pulmonary function in children with
      cystic fibrosis.
AB  - AIM: To measure the weight and height of children with cystic fibrosis (CF) from
      2 to 10 years of age and to investigate the relationship between these parameters
      and forced expiratory volume in 1 sec (FEV1) beginning at 6 years of age.
      METHODS: Weight and height were expressed as z-scores for weight-for-age (WFA),
      height-for-age (HFA), height-adjusted-for-target-height (HFA/TH) and weight-for
      height (WFH). The children were categorised as having a z-score >=0, between 0
      and -1, or <-1 based on z-scores at 2 years of age. The cross-sectional and
      longitudinal relationships between FEV1 and WFA, HFA, HFA/TH and WFH were
      determined and the predictive value of these parameters for FEV1. RESULTS: We
      enrolled 156 CF children. Their mean weight and height were below the average for
      the healthy population. Both WFA and WFH increased with age (primarily before the
      age of 6), while the reduction in HFA and HFA/TH persisted. Importantly, the
      yearly decline in FEV1 was significantly slowed [by 1.8 and 1.9% for each unit
      increase in WFA and WFH (p < 0.015)] in children who gained weight. CONCLUSION:
      CF patients aged 2 to 10 years have long-term impaired growth. Nevertheless,
      weight gain slowed the decline in FEV1 in these patients.

PMID- 24117797
TI  - Significantly higher frequency of Helicobacter suis in patients with idiopathic
      parkinsonism than in control patients.
AB  - BACKGROUND: There is increased proportional mortality from Parkinson's disease
      amongst livestock farmers. The hypokinesia of Parkinson's disease has been linked
      to Helicobacter pylori. H. suis is the most common zoonotic helicobacter in man.
      AIM: To compare the frequency of H. suis, relative to H. pylori, in gastric
      biopsies of patients with idiopathic parkinsonism (IP) and controls from
      gastroenterology services. METHODS: DNA extracts, archived at a Helicobacter
      Reference Laboratory, from IP patient and gastroenterology service biopsies were
      examined anonymously for H. suis, using species-specific RT-PCR. RESULTS:
      Relative risk of having H. suis in 60 IP patients compared with 256 controls was
      10 times greater than that of having H. pylori. In patients with IP and controls,
      respectively, frequencies of H. suis were 27 (exact binomial 95% C.I. 15, 38) and
      2 (0, 3)%, and of H. pylori, 28 (17, 40) and 16 (12, 21)%. Excess of H. suis in
      IP held when only the antral or corporal biopsy was considered. Of 16 IP patients
      with H. suis, 11 were from 19 with proven H. pylori eradication, 3 from 17 pre-H.
      pylori eradication, 2 from 24 H. pylori culture/PCR-negative. Frequency was
      different between groups (P = 0.001), greatest where H. pylori had been
      eradicated. Even without known exposure to anti-H. pylori therapy, H. suis was
      more frequent in IP patients (5/41) than in controls (1/155) (P = 0.002). Partial
      multilocus sequence typing confirmed that strains from IP patients (6) and
      control (1) differed from RT-PCR standard strain. CONCLUSIONS: Greater frequency
      of H. suis in idiopathic parkinsonism appears exaggerated following H. pylori
      eradication. Multilocus sequence testing comparison with porcine strains may
      clarify whether transmission is from pigs/porcine products or of human-adapted,
      H. suis-like, bacteria.

PMID- 24117798
TI  - Screening biological stains with qPCR versus lateral flow immunochromatographic
      test strips: a quantitative comparison using analytical figures of merit.
AB  - Biological fluid identification is an important facet of evidence examination in
      forensic laboratories worldwide. While identifying bodily fluids may provide
      insight into which downstream DNA methods to employ, these screening techniques
      consume a vital portion of the available evidence, are usually qualitative, and
      rely on visual interpretation. In contrast, qPCR yields information regarding the
      amount and proportion of amplifiable genetic material. In this study, dilution
      series of either semen or male saliva were prepared in either buffer or female
      blood. The samples were subjected to both lateral flow immunochromatographic test
      strips and qPCR analysis. Analytical figures of merit-including sensitivity,
      minimum distinguishable signal (MDS) and limit of detection (LOD)-were calculated
      and compared between methods. By applying the theory of the propagation of random
      errors, LODs were determined to be 0.05 MUL of saliva for the RSIDTM Saliva
      cards, 0.03 MUL of saliva for Quantifiler((r)) Duo, and 0.001 MUL of semen for
      Quantifiler((r)) Duo. In conclusion, quantitative PCR was deemed a viable and
      effective screening method for subsequent DNA profiling due to its stability in
      different matrices, sensitivity, and low limits of detection.

PMID- 24117799
TI  - Pathogen inactivation and removal methods for plasma-derived clotting factor
      concentrates.
AB  - Pathogen safety is crucial for plasma-derived clotting factor concentrates used
      in the treatment of bleeding disorders. Plasma, the starting material for these
      products, is collected by plasmapheresis (source plasma) or derived from whole
      blood donations (recovered plasma). The primary measures regarding pathogen
      safety are selection of healthy donors donating in centers with appropriate
      epidemiologic data for the main blood-transmissible viruses, screening donations
      for the absence of relevant infectious blood-borne viruses, and release of plasma
      pools for further processing only if they are nonreactive for serologic markers
      and nucleic acids for these viruses. Despite this testing, pathogen inactivation
      and/or removal during the manufacturing process of plasma-derived clotting factor
      concentrates is required to ensure prevention of transmission of infectious
      agents. Historically, hepatitis viruses and human immunodeficiency virus have
      posed the greatest threat to patients receiving plasma-derived therapy for
      treatment of hemophilia or von Willebrand disease. Over the past 30 years,
      dedicated virus inactivation and removal steps have been integrated into factor
      concentrate production processes, essentially eliminating transmission of these
      viruses. Manufacturing steps used in the purification of factor concentrates have
      also proved to be successful in reducing potential prion infectivity. In this
      review, current techniques for inactivation and removal of pathogens from factor
      concentrates are discussed. Ideally, production processes should involve a
      combination of complementary steps for pathogen inactivation and/or removal to
      ensure product safety. Finally, potential batch-to-batch contamination is avoided
      by stringent cleaning and sanitization methods as part of the manufacturing
      process. 

PMID- 24117800
TI  - Dental visiting history between ages 13 and 30 years and oral health-related
      impact.
AB  - BACKGROUND: The aim was to assess the role of visit history factors between the
      age of 13 and 30 years on oral health-related impact. MATERIALS AND METHODS: In
      1988-89, n=7,673 South Australian school children aged 13 years were sampled with
      n=4,604 children (60.0%) and n=4,476 parents (58.3%) returning questionnaires. In
      2005-06, n=632 baseline study participants responded (43.0% response of those
      traced and living in Adelaide). Oral health impact was measured at age 30 years
      using OHIP-14. RESULTS: Multivariate regression showed that OHIP scores were
      significantly higher (P<0.05) for those with episodes of relief of pain visits
      once (beta=1.487) or two or more times (beta=2.883), and episodes of extraction
      once (beta=1.301) or two or more times (beta=3.172). Higher positive dental visit
      attitude scores were associated with lower OHIP scores (beta=-1.265), as were
      being male (beta=-0.637), having a job (beta=-1.555) and being tertiary educated
      (beta=-0.632). CONCLUSIONS: History of adverse dental events between the age of
      13 and 30 years such as episodes of relief of pain visits and episodes of
      extraction was associated with higher impact of oral health problems at age 30
      suggesting a cumulative effect.

PMID- 24117801
TI  - Genomic editing opens new avenues for zebrafish as a model for neurodegeneration.
AB  - Zebrafish has become a popular model organism to study human diseases. We will
      highlight the advantages and limitations of zebrafish as a model organism to
      study neurodegenerative diseases and introduce zinc finger nucleases,
      transcription activator-like effector nucleases, and the recently established
      clustered regularly interspaced short palindromic repeats/clustered regularly
      interspaced short palindromic repeat-associated system for genome editing. The
      efficiency of the novel genome editing tools now greatly facilitates knock-out
      and, importantly, also makes knock-in approaches feasible in zebrafish. Genome
      editing in zebrafish avoids unspecific phenotypes caused by off-target effects
      and toxicity as frequently seen in conventional knock-down approaches. 

PMID- 24117802
TI  - Mycorrhizas and New Phytologist: une vraie histoire d'amour.

PMID- 24117803
TI  - Healing and closure following death: death signals from a wounded leaf.

PMID- 24117804
TI  - Elegant biochemistry, chaotic origin.

PMID- 24117805
TI  - Scaling climate change experiments across space and time.

PMID- 24117806
TI  - Changes in free-living bacterial community diversity reflect the magnitude of
      environmental variability.
AB  - A 2-year study was undertaken to compare patterns in the diversity of free-living
      bacteria in a river-dominated estuary and offshore, on the shelf, to determine
      whether changes in the free-living bacterial community could be related to
      differences in environmental seasonality and variability. Although the
      environmental conditions inshore were significantly more variable than those on
      the shelf and demonstrated clear seasonal patterns, there were no significant
      differences in the alpha diversity of the communities based on richness,
      evenness, or phylogenetic diversity. Comparison of communities using Bray-Curtis
      similarity indicated no significant differences in the magnitude of change
      between sequential samples from inshore and on the shelf. Seasonal differences
      were detected both inshore and on the shelf. However, analysis using the weighted
      UniFrac distance indicated significantly lower overall change between shelf
      samples with no significant seasonal differences. These findings suggest
      different patterns of change between the two sites. Inshore, changes in the
      relative abundance of distantly related bacterial species reflect the larger
      environmental variability, while on the shelf, changes in the relative abundance
      of closely related bacterial species or strains may result in a more functionally
      stable community. Thus, the magnitude of environmental change can alter patterns
      of bacterial diversity in marine systems.

PMID- 24117807
TI  - Longitudinal relations between maternal depressive symptoms and child sleep
      problems: the role of parasympathetic nervous system reactivity.
AB  - BACKGROUND: We examined maternal depressive symptoms (MDS) as longitudinal
      predictors of actigraphy-measured sleep; children's respiratory sinus arrhythmia
      (RSA) was tested as a moderator of these relations. METHOD: A total of 271
      children (145 boys and 126 girls) participated in a three-wave study (M age at T1
      = 9.38 years), with a 1-year lag between waves. Children wore actigraphs to
      derive sleep parameters. RSA reactivity was assessed during a social stress test.
      RESULTS: Contrary to hypotheses, MDS were related to less sleep over time for
      children exhibiting greater RSA withdrawal. Consistent with hypotheses, MDS were
      related longitudinally to decreased sleep activity for children exhibiting less
      RSA withdrawal. CONCLUSIONS: Findings illustrate the importance of maternal
      influences and physiological regulation as predictors of children's sleep.

PMID- 24117808
TI  - Exclusive breastfeeding for 4 versus 6 months and growth in early childhood.
AB  - AIM: To investigate the growth and the prevalence of overweight in early
      childhood among infants exclusively breastfed for 6 months (EBF) compared with
      those receiving complementary foods from 4 months of age in addition to breast
      milk (CF). METHODS: A total of 119 mother-infant pairs were randomised either in
      the CF or in the EBF group. Weight, length and head circumference of the infants
      were measured at birth, 6 weeks, and 3-6 months of age. In the follow-up, the
      children's weight, length and head circumference were measured at 8, 10, 12 and
      18 months and weight and height at 29-38 months. RESULTS: There were no
      differences between groups in the anthropometric outcome measures of weight-for
      age (p = 0.78), length-for-age (p = 0.59), head-circumference-for-age (p = 0.82)
      and BMI-for-age (p = 0.61), using repeated measurements ANOVA. Furthermore, no
      difference was seen in the prevalence between groups in risk of being overweight
      or in those who were overweight at 18 months and 29-38 months of age. CONCLUSION:
      Exclusive breastfeeding for the first 4 or 6 months of life does not seem to
      affect the risk of being overweight or the prevalence of those who were
      overweight in early childhood.

PMID- 24117809
TI  - Cytoskeletal function in the immune system.

PMID- 24117810
TI  - Wiskott-Aldrich syndrome protein--dynamic regulation of actin homeostasis: from
      activation through function and signal termination in T lymphocytes.
AB  - The actin cytoskeleton network forms a key link between T-cell antigen receptor
      (TCR) stimulation and T-cell effector functions, providing a structural basis for
      T-cell morphological changes and signal transduction. Accumulating evidence
      positions the Wiskott-Aldrich syndrome protein (WASp), a scaffolding protein that
      promotes actin polymerization, at the center of actin cytoskeleton-dependent T
      cell function. During the past decade, we and others have utilized
      multidisciplinary technologies, including live-cell imaging, biochemical, and
      biophysical analyses, to gain insight into the mechanisms by which WASp and other
      cytoskeletal proteins control actin homeostasis. Following TCR engagement, WASp
      is rapidly activated and recruited to TCR microclusters, as part of multiprotein
      complexes, where it promotes actin remodeling. Late in the activation process,
      WASp is internalized and eventually degraded. In this review, we describe the
      dynamic interactions of WASp with signaling proteins, which regulate its
      activation and recruitment to the TCR and to actin-rich sites. Finally, we
      present the molecular mechanism of WASp downregulation. Some of the signaling
      proteins that mediate WASp activation eventually lead to its degradation. Thus,
      we focus here on the regulation of WASp expression and function and the
      mechanisms whereby they control actin machinery and T-cell effector functions. 

PMID- 24117811
TI  - Cofilin: a redox sensitive mediator of actin dynamics during T-cell activation
      and migration.
AB  - Cofilin is an actin-binding protein that depolymerizes and/or severs actin
      filaments. This dual function of cofilin makes it one of the major regulators of
      actin dynamics important for T-cell activation and migration. The activity of
      cofilin is spatio-temporally regulated. Its main control mechanisms comprise a
      molecular toolbox of phospho-, phospholipid, and redox regulation. Phosphorylated
      cofilin is inactive and represents the dominant cofilin fraction in the cytoplasm
      of resting human T cells. A fraction of dephosphorylated cofilin is kept inactive
      at the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate.
      Costimulation via the T-cell receptor/CD3 complex (signal 1) together with
      accessory receptors (signal 2) or triggering through the chemokine SDF1alpha
      (stromal cell-derived factor 1alpha) induce Ras-dependent dephosphorylation of
      cofilin, which is important for immune synapse formation, T-cell activation, and
      T-cell migration. Recently, it became evident that cofilin is also highly
      sensitive for microenvironmental changes, particularly for alterations in the
      redox milieu. Cofilin is inactivated by oxidation, provoking T-cell
      hyporesponsiveness or necrotic-like programmed cell death. In contrast, in a
      reducing environment, even phosphatidylinositol 4,5-bisphosphate-bound cofilin
      becomes active, leading to actin dynamics in the vicinity of the plasma membrane.
      In addition to the well-established three signals for T-cell activation, this
      microenvironmental control of cofilin delivers a modulating signal for T-cell
      dependent immune reactions. This fourth modulating signal highly impacts both
      initial T-cell activation and the effector phase of T-cell-mediated immune
      responses.

PMID- 24117813
TI  - Re-defining ERM function in lymphocyte activation and migration.
AB  - Lymphocyte activation and migration involve large-scale actin cytoskeletal
      remodeling. The Ezrin-Radixin-Moesin (ERM) family proteins reversibly link the
      plasma membrane and cortical actin meshwork and mediate the dynamic nature of the
      membrane-cytoskeletal interface to facilitate remodeling. The reversibility of
      this linkage is controlled by the conformation of ERM proteins and depends on the
      phosphorylation of a conserved threonine residue in the actin-binding domain.
      Disruption of the phospho-cycling nature of ERM proteins through dominant
      negative and constitutively active mutants results in impaired lymphocyte
      migration and activation. In recent years, a novel role has emerged for ERM
      proteins as signaling scaffolds that can modulate B and T-cell activation through
      additional posttranslational modifications at tyrosine residues. Here, we
      highlight recent studies that have redefined the role of ERM proteins in
      lymphocyte activation and migration. We discuss how lymphocyte-specific knockouts
      of ERM proteins and high resolution imaging techniques have identified a novel
      function for them as rheostats that modulate the strength of antigen receptor
      signaling in B cells. Finally, we describe scenarios in which ERM protein
      function is coopted by pathogens for their own transmission and speculate on the
      potential of ERM proteins for regulating undesirable lymphocyte behaviors such as
      autoimmunity and malignancy. 

PMID- 24117812
TI  - The actin-bundling protein L-plastin supports T-cell motility and activation.
AB  - Tight regulation of actin dynamics is essential for T-cell trafficking and
      activation. Recent studies in human and murine T cells reveal that T-cell
      motility and full T-cell activation require the hematopoietic-specific, actin
      bundling protein L-plastin (LPL). T cells lacking LPL do not form fully mature
      synapses and thus demonstrate reduced cytokine production and proliferation.
      Reduction or loss of LPL expression also reduces the velocity of T cells and
      impairs thymic egress and intranodal motility. Whereas dispensable for proximal T
      cell receptor and chemokine receptor signaling, LPL is critical to the later
      stages of synapse maturation and cellular polarization. Serine phosphorylation,
      calcium, and calmodulin binding regulate the bundling activity and localization
      of LPL following T-cell receptor and chemokine receptor engagement. However, the
      interaction between these regulatory domains and resulting changes in local
      control of actin cytoskeletal structures has not been fully elucidated.
      Circumstantial evidence suggests a function for LPL in either the formation or
      maintenance of integrin-associated adhesion structures. As LPL may be a target of
      the commonly used immunosuppressive agent dexamethasone, full elucidation of the
      regulation and function of LPL in T-cell biology may illuminate new pathways for
      clinically useful immunotherapeutics. 

PMID- 24117817
TI  - Orchestrating cytoskeleton and intracellular vesicle traffic to build functional
      immunological synapses.
AB  - Immunological synapses are specialized cell-cell contacts formed between T
      lymphocytes and antigen-presenting cells. They are induced upon antigen
      recognition and are crucial for T-cell activation and effector functions. The
      generation and function of immunological synapses depend on an active T-cell
      polarization process, which results from a finely orchestrated crosstalk between
      the antigen receptor signal transduction machinery, the actin and microtubule
      cytoskeletons, and controlled vesicle traffic. Although we understand how some of
      these particular events are regulated, we still lack knowledge on how these
      multiple cellular elements are harmonized to ensure appropriate T-cell responses.
      We discuss here our view on how T-cell receptor signal transduction initially
      commands cytoskeletal and vesicle traffic polarization, which in turn sets the
      immunological synapse molecular design that regulates T-cell activation. We also
      discuss how the human immunodeficiency virus (HIV-1) hijacks some of these
      processes impairing immunological synapse generation and function. 

PMID- 24117814
TI  - Coordinate control of cytoskeletal remodeling and calcium mobilization during T
      cell activation.
AB  - Ca(2+) mobilization and cytoskeletal reorganization are key hallmarks of T-cell
      activation, and their interdependence has long been recognized. Recent advances
      in the field have elucidated the molecular pathways that underlie these events
      and have revealed several points of intersection. Ca(2+) signaling can be divided
      into two phases: initial events leading to release of Ca(2+) from endoplasmic
      reticulum stores, and a second phase involving STIM 1 (stromal interaction
      molecule 1) clustering and CRAC (calcium release activated calcium) channel
      activation. Cytoskeletal dynamics promote both phases. During the first phase,
      the actin cytoskeleton promotes mechanotransduction and serves as a dynamic
      scaffold for microcluster assembly. Proteins that drive actin polymerization such
      as WASp (Wiskott-Aldrich syndrome protein) and HS1 (hematopoietic lineage cell
      specific protein 1) promote signaling through PLCgamma1 (phospholipase Cgamma1)
      and release of Ca(2+) from endoplasmic reticulum stores. During the second phase,
      the WAVE (WASP-family verprolin homologous protein) complex and the microtubule
      cytoskeleton promote STIM 1 clustering at sites of plasma membrane apposition,
      opening Orai channels. In addition, gross cell shape changes and organelle
      movements buffer local Ca(2+) levels, leading to sustained Ca(2+) mobilization.
      Conversely, elevated intracellular Ca(2+) activates cytoskeletal remodeling. This
      can occur indirectly, via calpain activity, and directly, via Ca(2+) -dependent
      cytoskeletal regulatory proteins such as myosin II and L-plastin. While it is
      true that the cytoskeleton regulates Ca(2+) responses and vice versa,
      interdependence between Ca(2+) and the cytoskeleton also encompasses signaling
      events that occur in parallel, downstream of shared intermediates. Inositol
      cleavage by PLCgamma1 simultaneously triggers both endoplasmic reticulum store
      release and diacylglycerol-dependent microtubule organizing center reorientation,
      while depleting the pool of phosphatidylinositol-4,5-bisphosphate, an activator
      of multiple actin-regulatory proteins. The close interdependence of Ca(2+)
      signaling and cytoskeletal dynamics in T cells provides positive feedback
      mechanisms for T-cell activation and allows for finely tuned responses to
      extracellular cues. 

PMID- 24117818
TI  - The actin-driven spatiotemporal organization of T-cell signaling at the system
      scale.
AB  - T cells are activated through interaction with antigen-presenting cells (APCs).
      During activation, receptors and signaling intermediates accumulate in diverse
      spatiotemporal distributions. These distributions control the probability of
      signaling interactions and thus govern information flow through the signaling
      system. Spatiotemporally resolved system-scale investigation of signaling can
      extract the regulatory information thus encoded, allowing unique insight into the
      control of T-cell function. Substantial technical challenges exist, and these are
      briefly discussed herein. While much of the work assessing T-cell spatiotemporal
      organization uses planar APC substitutes, we focus here on B-cell APCs with often
      stark differences. Spatiotemporal signaling distributions are driven by cell
      biologically distinct structures, a large protein assembly at the interface
      center, a large invagination, the actin-supported interface periphery as extended
      by smaller individual lamella, and a newly discovered whole-interface actin
      driven lamellum. The more than 60 elements of T-cell activation studied to date
      are dynamically distributed between these structures, generating a complex
      organization of the signaling system. Signal initiation and core signaling prefer
      the interface center, while signal amplification is localized in the transient
      lamellum. Actin dynamics control signaling distributions through regulation of
      the underlying structures and drive a highly undulating T-cell/APC interface that
      imposes substantial constraints on T-cell organization. We suggest that the
      regulation of actin dynamics, by controlling signaling distributions and membrane
      topology, is an important rheostat of T-cell signaling.

PMID- 24117815
TI  - From lipid second messengers to molecular motors: microtubule-organizing center
      reorientation in T cells.
AB  - In T lymphocytes, polarization of the microtubule-organizing center (MTOC) to the
      immunological synapse enables the directional secretion of cytokines, cytolytic
      factors, and other soluble molecules toward the antigen-presenting cell. This is
      likely to be crucial for maintaining the specificity of T-cell effector
      responses. Here, we review recent advances in our understanding of MTOC
      reorientation in T cells, focusing first on the importance of diacylglycerol and
      protein kinase C isozymes and then on the molecular motor proteins that function
      downstream to drive MTOC movement. 

PMID- 24117816
TI  - The role of the cytoskeleton at the immunological synapse.
AB  - It has been over 30 years since the reorganization of both the microtubule
      network and a 'peculiar actin polarization' was reported at the contact area of
      cytotoxic T lymphocytes interacting with target cells. Since that time, hundreds
      of studies have been published in an effort to elucidate the structure and
      function of the microtubule network and the actin cytoskeleton in T-cell
      activation, migration, and effector function at the interface between a T cell
      and its cognate antigen-presenting cell or target cell. This interface has become
      known as the immunological synapse, and this review examines some of the roles
      played by the cytoskeleton at the synapse.

PMID- 24117819
TI  - Regulation of T-cell receptor signaling by the actin cytoskeleton and poroelastic
      cytoplasm.
AB  - The actin cytoskeleton plays essential roles in modulating T-cell activation.
      Most models of T-cell receptor (TCR) triggering signalosome assembly and immune
      synapse formation invoke actin-dependent mechanisms. As T cells are
      constitutively motile cells, TCR triggering and signaling occur against a
      cytoskeletal backdrop that is constantly remodeling. While the interplay between
      actin dynamics and TCR signaling have been the focus of research for many years,
      much of the work in T cells has considered actin largely for its 'scaffolding'
      function. We examine the roles of the actin cytoskeleton in TCR signaling and
      immune synapse formation with an emphasis on how poroelasticity, an ensemble
      feature of actin dynamics with the cytosol, relates to how T cells respond to
      stimulation. 

PMID- 24117822
TI  - Class I myosins in B-cell physiology: functions in spreading, immune synapses,
      motility, and vesicular traffic.
AB  - Myosins comprise a family of motor proteins whose role in muscle contraction and
      motility in a large range of eukaryotic cells has been widely studied. Although
      these proteins have been characterized extensively and much is known about their
      function in different cellular compartments, little is known about these
      molecules in hematopoietic cells. Myosins expressed by cells from the immune
      response are involved in maintaining plasma membrane tension, moving and
      secreting vesicles, endo- and exocytotic processes, and promoting the adhesion
      and motility of cells. Herein, we summarize our current understanding of class I
      myosins in B cells, with an emphasis on the emerging roles of these molecular
      motors in immune functions. 

PMID- 24117821
TI  - Actin-mediated feedback loops in B-cell receptor signaling.
AB  - Upon recognizing cognate antigen, B cells mobilize multiple cellular apparatuses
      to propagate an optimal response. Antigen binding is transduced into cytoplasmic
      signaling events through B-cell antigen receptor (BCR)-based signalosomes at the
      B-cell surface. BCR signalosomes are dynamic and transient and are subsequently
      endocytosed for antigen processing. The function of BCR signalosomes is one of
      the determining factors for the fate of B cells: clonal expansion, anergy, or
      apoptosis. Accumulating evidence underscores the importance of the actin
      cytoskeleton in B-cell activation. We have begun to appreciate the role of actin
      dynamics in regulating BCR-mediated tonic signaling and the formation of BCR
      signalosomes. Our recent studies reveal an additional function of the actin
      cytoskeleton in the downregulation of BCR signaling, consequently contributing to
      the generation and maintenance of B-cell self-tolerance. In this review, we
      discuss how actin remodels its organization and dynamics in close coordination
      with BCR signaling and how actin remodeling in turn amplifies the activation and
      subsequent downregulation process of BCR signaling, providing vital feedback for
      optimal BCR activation. 

PMID- 24117823
TI  - The central role of the cytoskeleton in mechanisms and functions of the NK cell
      immune synapse.
AB  - Natural killer (NK) cells discriminate between healthy and unhealthy target cells
      through a balance of activating and inhibitory signals at direct intercellular
      contacts called immune synapses. Rearrangements in the cellular cytoskeleton have
      long been known to be critical in assembly of immune synapses. Here, through
      bringing together the vast literature on this subject, the number of different
      ways in which the cytoskeleton is important becomes evident. The dynamics of
      filamentous actin are critical in (i) creating the nanometer-scale organization
      of NK cell receptors, (ii) establishing cellular polarity, (iii) coordinating
      immune receptor and integrin-mediated signaling, and (iv) directing secretion of
      lytic granules and cytokines. The microtubule network also is important in the
      delivery of lytic granules and vesicles containing cytokines to the immune
      synapse. Together, these data establish that the cytoskeleton acts as a central
      regulator of this complex and dynamic process - and an enormous amount of NK cell
      biology is controlled through the cytoskeleton. 

PMID- 24117820
TI  - Mechanical regulation of T-cell functions.
AB  - T cells are key players of the mammalian adaptive immune system. They experience
      different mechanical microenvironments during their life cycle, from the thymus,
      secondary lymph organs, and peripheral tissues that are free of externally
      applied force, but display variable substrate rigidities to the blood and
      lymphatic circulation systems, where complicated hydrodynamic forces are present.
      Regardless of whether T cells are subject to external forces or generate their
      own internal forces, they respond and adapt to different biomechanical cues to
      modulate their adhesion, migration, trafficking, and triggering of immune
      functions through mechanical regulation of various molecules that bear force.
      These include adhesive receptors, immunoreceptors, motor proteins, cytoskeletal
      proteins, and their associated molecules. Here, we discuss the forces acting on
      various surface and cytoplasmic proteins of a T cell in different mechanical
      milieus. We review existing data on how force regulates protein conformational
      changes and interactions with counter molecules, including integrins, actin, and
      the T-cell receptor, and how each relates to T-cell functions. 

PMID- 24117825
TI  - Migration of dendritic cells: physical principles, molecular mechanisms, and
      functional implications.
AB  - Dendritic cells (DCs) constitute a complex cell population that resides in both
      peripheral tissues and lymphoid organs. Their major function in tissues is to
      patrol their environment in search of danger-associated antigens to transport to
      lymph nodes and present to T lymphocytes. This process constitutes the first step
      of the adaptive immune response and relies on specific DC properties, including a
      high endocytic capacity as well as efficient motility in confined three
      dimensional environments. Although cell motility has been widely studied, little
      is known on how the geometric characteristics of the environment influence DC
      migration and function. In this review, we give an overview of the basic physical
      principles and molecular mechanisms that control DC migration under confinement
      and discuss how such mechanisms impact the environment-patrolling capacity of
      DCs. 

PMID- 24117824
TI  - Generation of membrane structures during phagocytosis and chemotaxis of
      macrophages: role and regulation of the actin cytoskeleton.
AB  - Macrophages are best known for their protective search and destroy functions
      against invading microorganisms. These processes are commonly known as chemotaxis
      and phagocytosis. Both of these processes require actin cytoskeletal remodeling
      to produce distinct F-actin-rich membrane structures called lamellipodia and
      phagocytic cups. This review will focus on the mechanisms by which macrophages
      regulate actin polymerization through initial receptor signaling and subsequent
      Arp2/3 activation by nucleation-promoting factors like the WASP/WAVE family,
      followed by remodeling of actin networks to produce these very distinct
      structures. 

PMID- 24117826
TI  - Rho GTPases control specific cytoskeleton-dependent functions of hematopoietic
      stem cells.
AB  - The Rho family of guanosine triphosphatases (GTPases) is composed of members of
      the Ras superfamily of proteins. They are GTP-bound molecules with a modest
      intrinsic GTPase activity that can be accelerated upon activation/localization of
      specialized guanine nucleotide exchange factors. Members of this family act as
      molecular switches and are required for coordinated cytoskeletal rearrangements
      that are crucial in a set of specialized functions of mammalian stem cells. These
      functions include self-renewal, adhesion, and migration. Mouse gene-targeting
      studies have provided convincing evidence of the indispensable and dispensable
      roles of individual members of the Rho GTPase family and the putative upstream
      and downstream mediators in stem cell-specific functions. The role of Rho GTPases
      and related signaling pathways previously seen in other cell types and organisms
      have been confirmed in mammalian hematopoietic stem cells (HSCs), and new
      signaling pathways and unexpected functions unique to HSCs have been identified
      and dissected. This review summarizes our current understanding of the role of
      Rho family of GTPases on HSC and progenitor activity through cytoskeleton
      mediated signaling pathways, providing insight about relevant signaling pathways
      that regulate mammalian stem cell self-renewal, adhesion, and migration. 

PMID- 24117827
TI  - Neutrophil migration: moving from zebrafish models to human autoimmunity.
AB  - There has been a resurgence of interest in the neutrophil's role in autoimmune
      disease. Classically considered an early responder that dies at the site of
      inflammation, new findings using live imaging of embryonic zebrafish and other
      modalities suggest that neutrophils can reverse migrate away from sites of
      inflammation. These 'inflammation-sensitized' neutrophils, as well as the
      neutrophil extracellular traps and other products made by neutrophils in general,
      may have many implications for autoimmunity. Here, we review what is known about
      the role of neutrophils in three different autoimmune diseases: rheumatoid
      arthritis, systemic lupus erythematosus, and small vessel vasculitis. We then
      highlight recent findings related to several cytoskeletal regulators that guide
      neutrophil recruitment including Lyn, Rac2, and SHIP. Finally, we discuss how our
      improved understanding of the molecules that control neutrophil chemotaxis may
      impact our knowledge of autoimmunity. 

PMID- 24117830
TI  - Undergraduate curriculum guidelines for endodontology.

PMID- 24117831
TI  - Molecular characterization of the beta-lactamases in Escherichia coli and
      Klebsiella pneumoniae from a tertiary care hospital in Riyadh, Saudi Arabia.
AB  - The widespread use of antimicrobials has increased the occurrence of multidrug
      resistant microbes. The commonest mechanism of antimicrobial resistance in
      Enterobacteriaceae is production of beta-lactamases such as metallo-beta
      lactamases (MBL) and extended spectrum beta-lactamases (ESBL). Few studies have
      used a molecular approach to characterize the prevalence of beta-lactamases.
      Here, the prevalence of different beta-lactamases was characterized by performing
      three multiplex PCRs targeting genes similar to those described in earlier
      publications. Antimicrobial susceptibility tests for all isolates were performed
      using the agar dilution method. beta-lactamase was detected in 72% of the
      isolates, the detection rate being 64% in 2011 and 75% in 2012. The isolates were
      highly resistant to carbapenems such as meropenem and imipenem and susceptible to
      colistin and tigecycline. In this study, 22% of isolates contained both MBL and
      ESBL. ESBL was detected more frequently in Escherichia coli isolates, whereas
      carbapenemase was detected more frequently in Klebsiella pneumoniae isolates.
      These findings suggest the spread of multi-resistant ESBL and MBL producers in
      the community. Our results have implications for patient treatment and also
      indicate the need for increased surveillance and molecular characterization of
      isolates. 

PMID- 24117832
TI  - Understanding the pharmacokinetics of tulathromycin: a pulmonary perspective.
AB  - Tulathromycin is approved in the United States for the treatment of respiratory
      disease in bovine and swine, infectious bovine keratoconjunctivitis associated
      with Moraxella bovis, and interdigital necrobacillosis in bovine. This macrolide
      highly concentrates in lung tissue and persists in the intra-airway compartment
      for a long time after a single administration. It also accumulates in
      inflammatory cells, including neutrophils and macrophages. This article reviews
      pharmacokinetic information about tulathromycin in different veterinary species
      with particular emphasis on the respiratory system. 

PMID- 24117828
TI  - Actin cytoskeletal defects in immunodeficiency.
AB  - The importance of the cytoskeleton in mounting a successful immune response is
      evident from the wide range of defects that occur in actin-related primary
      immunodeficiencies (PIDs). Studies of these PIDs have revealed a pivotal role for
      the actin cytoskeleton in almost all stages of immune system function, from
      hematopoiesis and immune cell development, through to recruitment, migration,
      intercellular and intracellular signaling, and activation of both innate and
      adaptive immune responses. The major focus of this review is the immune defects
      that result from mutations in the Wiskott-Aldrich syndrome gene (WAS), which have
      a broad impact on many different processes and give rise to clinically
      heterogeneous immunodeficiencies. We also discuss other related genetic defects
      and the possibility of identifying new genetic causes of cytoskeletal
      immunodeficiency. 

PMID- 24117833
TI  - BRAF mutation in 'sarcomas': a possible method to detect de-differentiated
      melanomas.
AB  - AIMS: BRAF is mutated in 50-60% of melanomas, but BRAF mutation in sarcomas has
      not been systematically evaluated. Some melanomas are spindled and may show no
      immunohistochemical evidence of melanocytic differentiation. Similarly, many
      sarcomas are undifferentiated, i.e. undifferentiated pleomorphic sarcomas (UPS).
      Diagnosing melanoma versus sarcoma in an undifferentiated spindle cell malignancy
      can be challenging. Our aim was to evaluate the prevalence of BRAF mutation in
      sarcomas and the use of BRAF mutational status in the diagnosis of spindle cell
      malignancies. METHODS AND RESULTS: BRAF mutational analysis was performed on
      tissue from 104 patients: 90 with sarcoma only (50 UPS) and 14 with sarcoma and
      melanoma (seven UPS). In the sarcoma-only group, BRAF mutation was absent. In the
      sarcoma-melanoma group, three sarcomas showed BRAF mutation; all were UPS,
      occurred after the melanomas and did not stain for melanocytic markers. One
      melanoma-sarcoma pair showed identical BRAF V600E mutations. CONCLUSIONS: The
      presence of BRAF mutation in these tumours raises the possibility that poorly
      differentiated spindle cell malignancies with BRAF mutation may represent
      melanomas, and BRAF mutational analysis should be considered in a patient with a
      spindle cell malignancy and a history of melanoma, as a positive result may
      indicate de-differentiated melanoma.

PMID- 24117829
TI  - Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory
      pathways.
AB  - The human immunodeficiency virus-1 (HIV-1) infects helper CD4(+) T cells, and
      causes CD4(+) T-cell depletion and immunodeficiency. In the past 30 years,
      significant progress has been made in antiretroviral therapy, and the disease has
      become manageable. Nevertheless, an effective vaccine is still nowhere in sight,
      and a cure or a functional cure awaits discovery. Among possible curative
      therapies, traditional antiretroviral therapy, mostly targeting viral proteins,
      has been proven ineffective. It is possible that targeting HIV-dependent host
      cofactors may offer alternatives, both for preventing HIV transmission and for
      forestalling disease progression. Recently, the actin cytoskeleton and its
      regulators in blood CD4(+) T cells have emerged as major host cofactors that
      could be targeted. The novel concept that the cortical actin is a barrier to
      viral entry and early post-entry migration has led to the nascent model of virus
      host interaction at the cortical actin layer. Deciphering the cellular regulatory
      pathways has manifested exciting prospects for future therapeutics. In this
      review, we describe the study of HIV interactions with actin cytoskeleton. We
      also examine potential pharmacological targets that emerge from this interaction.
      In addition, we briefly discuss several actin pathway-based anti-HIV drugs that
      are currently in development or testing.

PMID- 24117834
TI  - Postoperative management of severe acute anemia in a Jehovah's Witness.
AB  - BACKGROUND: Low levels of hemoglobin (Hb) are not rare in patients who refuse
      blood components but this case is unique due to the severity of anemia and the
      possibility that her previous episode of acute normovolemic hemodilution has
      influenced her outcome. CASE REPORT: We report an incident involving acute blood
      loss after surgery with an extremely low hematocrit. Despite her Hb levels (2.8
      g/dL) she remained lucid, expressing her wish not to receive transfusion. When
      the patient lost consciousness (Hb, 1.4 g/dL) she was promptly sedated,
      curarized, and put onto mechanical controlled ventilation. Aggressive
      erythropoietin therapy increased the patient's Hb level by 240% in 10 days,
      despite a high platelet count. This case demonstrates that critical levels of
      oxygen delivery may be lower than previously thought possible. CONCLUSION: This
      case is an example of the resilience of the human body in an extreme
      circumstance. It might be the most severe case of anemia that a person has
      survived without any sequelae.

PMID- 24117835
TI  - Alcoholic fermentation induces melatonin synthesis in orange juice.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple
      biological functions. Its level decreases with age, and the intake of foods rich
      in melatonin has been considered an exogenous source of this important agent.
      Orange is a natural source of melatonin. Melatonin synthesis occurs during
      alcoholic fermentation of grapes, malt and pomegranate. The amino acid tryptophan
      is the precursor of all 5-methoxytryptamines. Indeed, melatonin appears in a
      shorter time in wines when tryptophan is added before fermentation. The aim of
      the study was to measure melatonin content during alcoholic fermentation of
      orange juice and to evaluate the role of the precursor tryptophan. Identification
      and quantification of melatonin during the alcoholic fermentation of orange juice
      was carried out by UHPLC-QqQ-MS/MS. Melatonin significantly increased throughout
      fermentation from day 0 (3.15 ng/mL) until day 15 (21.80 ng/mL) reaching larger
      amounts with respect to other foods. Melatonin isomer was also analysed, but its
      content remained stable ranging from 11.59 to 14.18 ng/mL. The enhancement of
      melatonin occurred mainly in the soluble fraction. Tryptophan levels
      significantly dropped from 13.80 mg/L (day 0) up to 3.19 mg/L (day 15) during
      fermentation. Melatonin was inversely and significantly correlated with
      tryptophan (r = 0.907). Therefore, the enhancement in melatonin could be due to
      both the occurrence of tryptophan and the new synthesis by yeast. In summary, the
      enhancement of melatonin in novel fermented orange beverage would improve the
      health benefits of orange juice by increasing this bioactive compound.

PMID- 24117836
TI  - Emergence of Vibrio cholerae O1 classical biotype in 2012 in Iran.
AB  - Cholera outbreaks annually occur in many parts of Iran. The aim of this study was
      to investigate the biotype and genotype diversity of V. cholerae isolates from
      recent outbreak (2012) in Iran and to characterize the ctxB allelic sequence of
      isolates. The ctxB sequence of all isolates was analyzed and compared with the
      reference ctxB sequences for El Tor and classical biotypes in GenBank database.
      The PFGE genotype specification of isolates was determined and genetic
      relatedness among isolates and also with those previously reported from Iran was
      assessed. Ten out of eleven isolates were identified as El Tor biotype and one
      single isolate belonged to classical biotype. All isolates except three possessed
      tcpA, ctxA, ctxB and wbeT genes. All the ctxB(+) isolates in this study
      (classical and El Tor biotypes) possessed the ctxB sequence of classical biotype
      allele providing evidences of El Tor variants. Eight out of 11 isolates (73%)
      showed identical pulsotypes (P1). Each of the remaining three isolates showed
      distinct pulsotypes (P2-P4) with more than three band differences. Pulsotype P2
      was corresponded to an isolate (9%) with classical biotype. The result
      demonstrated diversity in virulence gene content of strains with identical PFGE
      patterns and also provided evidences of the import of a V. cholerae strain with
      classical biotype from out of our country as no classical biotype strain has been
      previously (1998-2011) reported from Iran. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Emergence of V. cholerae with Classical biotype after at least one decade in Iran
      is alarming due to fear of expansion of V. cholerae strains with high virulence
      potential and signifies the need to monitor and analyze all new cases in
      countries with cholera outbreaks or even sporadic cases as this could conceivably
      affect the neighbouring countries and may expose the world to the seventh
      pandemic with Classical biotype strains.

PMID- 24117837
TI  - Cost-effectiveness of using Quantiferon Gold (QFT-G)(r) versus tuberculin skin
      test (TST) among U.S. and foreign born populations at a public health department
      clinic with a low prevalence of tuberculosis.
AB  - OBJECTIVE: The purpose of this study was to determine the cost benefit to
      routinely using QFT-G versus the standard TST for screening U.S. and foreign born
      populations at a public health department clinic with a low prevalence of
      tuberculosis. DESIGN AND SAMPLE: A comparative cost analysis of the monetization
      between QFT-G and TST was conducted: Data from the health department's Chest
      Clinic patients seen in 2007 were used to model cost predictions. MEASURES: The
      net costs of screening, x-rays, the standard 9 months of latent tuberculosis
      infection treatment, laboratory, and administration for U.S. born patients and
      foreign born patients were investigated. RESULTS: There are no apparent cost
      savings for U.S. born individuals, but due to the higher specificity of QFT-G for
      foreign born BCG-vaccinated individuals, there are unnecessary expenditures
      associated with the higher number of false positives incurred when using TST
      compared with QFT-G on 1,000 foreign born individuals (69%, 18%). CONCLUSION: QFT
      G is cost-effective and should be used at local health department clinics that
      want to achieve savings in screening and treating those suspected of having TB
      infection, especially for high-risk populations such as foreign born individuals.

PMID- 24117838
TI  - The role of family functioning in childhood dental caries.
AB  - OBJECTIVES: This study investigated the relationship between family functioning
      and childhood dental caries. Further objectives were (i) to explore whether oral
      hygiene behaviours could account for a possible association between family
      functioning dimensions and childhood dental caries and (ii) to explore whether
      family functioning could mediate the relationship between sociodemographic
      factors and childhood dental caries. METHODS: A random sample of 630 5- to 6-year
      old children was recruited from six large paediatric dental centres in the
      Netherlands. Children's dmft scores were extracted from personal dental records.
      A parental questionnaire and the Gezinsvragenlijst (translation: Family
      Questionnaire) were used to collect data on sociodemographic characteristics,
      oral hygiene behaviours and family functioning. Family functioning was assessed
      on five dimensions: responsiveness, communication, organization, partner-relation
      and social network. Associations with dmft were analysed using multilevel
      modelling. RESULTS: Bivariate analysis showed that children from normal
      functioning families on the dimensions responsiveness, communication,
      organization and social network had significantly lower dmft scores compared with
      children from dysfunctional families. Poorer family functioning on all dimensions
      was associated with an increased likelihood of engaging in less favourable oral
      hygiene behaviours. Children with lower educated mothers, immigrant children and
      children of higher birth order were more likely to come from poorer functioning
      families. In multivariate analysis, organization remained a significant predictor
      of dmft after adjusting for the other family functioning dimensions and the
      mother's education level, but it lost statistical significance after adjustment
      for oral hygiene behaviours. CONCLUSION: A relationship between family
      functioning and childhood dental caries was found, which may have operated via
      oral hygiene behaviours. Family functioning modestly explained socioeconomic
      inequalities in child oral health. Organization appeared to be the most important
      dimension of family functioning that influenced children's caries experience.

PMID- 24117839
TI  - Bayesian treatment of model uncertainty for partially applicable models.
AB  - This article discusses how analyst's or expert's beliefs on the credibility and
      quality of models can be assessed and incorporated into the uncertainty
      assessment of an unknown of interest. The proposed methodology is a
      specialization of the Bayesian framework for the assessment of model uncertainty
      presented in an earlier paper. This formalism treats models as sources of
      information in assessing the uncertainty of an unknown, and it allows the use of
      predictions from multiple models as well as experimental validation data about
      the models' performances. In this article, the methodology is extended to
      incorporate additional types of information about the model, namely, subjective
      information in terms of credibility of the model and its applicability when it is
      used outside its intended domain of application. An example in the context of
      fire risk modeling is also provided. 

PMID- 24117840
TI  - Downregulation of polymeric immunoglobulin receptor and secretory IgA antibodies
      in eosinophilic upper airway diseases.
AB  - BACKGROUND: Immunoglobulin (Ig) A represents a first-line defence mechanism in
      the airways, but little is known regarding its implication in upper airway
      disorders. This study aimed to address the hypothesis that polymeric Ig receptor
      (pIgR)-mediated secretory IgA immunity could be impaired in chronic upper airway
      diseases. METHODS: Nasal and ethmoidal biopsies, as well as nasal secretions,
      were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps
      (CRSwNP) or without nasal polyps (CRSsNP), allergic rhinitis (AR) and controls,
      and assayed for IgA1/IgA2 synthesis, pIgR expression, production of secretory
      component (SC), IgA and relevant IgA antibodies, and correlated with local
      eosinophils and inflammatory features (IL-12, IL-13 and ECP). RESULTS: pIgR
      expression was decreased in the ethmoidal mucosa in patients with CRSwNP (P =
      0.003) and in AR (P = 0.006). This pIgR defect was associated with reduced levels
      of SC (P = 0.007) and IgA antibodies to Staphylococcus aureus enterotoxin B
      (SAEB) (P = 0.003) in nasal secretions from patients with CRSwNP, and with
      increased IgA deposition in subepithelial areas. pIgR downregulation was
      selectively observed in patients with tissue eosinophilia, whilst no clear
      relation to smoking history was observed. CONCLUSION: Epithelial pIgR expression
      is decreased in patients with CRSwNP and AR and results in decreased SC and IgA
      antibodies to certain bacterial antigens (SAEB) in nasal secretions of patients
      with CRSwNP in parallel to subepithelial accumulation of IgA. This defect in
      mucosal immunity is associated with eosinophilic, Th2-related inflammation.

PMID- 24117841
TI  - Associations between diet-related diseases and impaired physiological mechanisms:
      a holistic approach based on meta-analyses to identify targets for preventive
      nutrition.
AB  - In nutrition research, analyzing the relationship between a diet-related chronic
      disease and impaired metabolism is a common reductionist approach. Meta-analyses
      have enabled quantification of these relationships. There is, however, a need for
      more holistic approaches to determine the sequence of connections between
      diseases and associated physiological mechanisms. The objective of this
      exhaustive review was to collect scientific evidence - with priority given to
      quantitative reviews - published between 1950 and 2011 to assess the
      relationships between major diet-related chronic diseases and deregulated
      mechanisms. The results revealed that diabetes and obesity are the key diseases
      that lead to all other diet-related chronic diseases, while cancer,
      cardiovascular disease, skeletal disease, and sarcopenia are endpoint diseases.
      Liver disease, kidney disease, digestive disease, and mental illness are
      consequences as well as causes of other diet-related chronic diseases. All
      diseases have multifactorial causes, and most result from decreased antioxidant
      status, acid-base imbalance, increased inflammatory status, impaired
      carbohydrate/lipid/one-carbon metabolism, impaired functioning of neurons and DNA
      transcription, hypertension, and/or modified digestive microflora. Nutritional
      strategies that focus on the prevention of obesity and diabetes should be
      prioritized in order to reduce the prevalence of other major chronic diseases.

PMID- 24117842
TI  - SALL4 immunohistochemistry in non-small-cell lung carcinomas.

PMID- 24117843
TI  - The role of vitreous magnesium quantification in estimating the postmortem
      interval.
AB  - The use of magnesium as a parameter to estimate the time of death is
      controversial. In 32 traumatic deaths with known postmortem intervals (PMIs),
      small quantities of vitreous humor (VH) were sampled repetitively every 3 h until
      24 h postmortem. The bodies were kept at the constant ambient temperature of 20
      degrees C (68 degrees F). The concentrations of magnesium were in the range of
      0.47-1.15 mM. A statistically significant correlation of the concentration of
      magnesium with the PMI was observed (r = 0.453, p < 0.01), but with small
      predictive value--coefficient of variation for regression was 45.5%; the average
      of the paired differences between the estimated and actual PMIs was 5.24 + 3.19
      h. Although useful results might be expected due to the large transmembrane
      gradient for magnesium, the results of this study strongly disprove the
      usefulness of measuring magnesium in VH to estimate the time of death.

PMID- 24117844
TI  - Qualitative and quantitative evaluation of avian demineralized bone matrix in
      heterotopic beds.
AB  - OBJECTIVE: To evaluate the osteogenic potential of avian demineralized bone
      matrix (DBM) in the context of implant geometry. STUDY DESIGN: Experimental.
      ANIMALS: Rock pigeons (n = 24). METHODS: Tubular and chipped forms of DBM were
      prepared by acid demineralization of long bones from healthy allogeneic donors
      and implanted bilaterally into the pectoral region of 24 pigeons. After
      euthanasia at 1, 4, 6, 8, 10, and 12 weeks, explants were evaluated
      histologically and compared by means of quantitative (bone area) and semi
      quantitative measures (scores). RESULTS: All explants had new bone at retrieval
      with the exception of tubular implants at the end of week 1. The most reactive
      part in both implants was the interior region between the periosteal and
      endosteal surfaces followed by the area at the implant-muscle interface.
      Quantitative measurements demonstrated a significantly (P = .012) greater
      percentage of new bone formation induced by tubular implants (80.28 +/- 8.94)
      compared with chip implants (57.64 +/- 3.12). There was minimal inflammation.
      CONCLUSIONS: Avian DBM initiates heterotopic bone formation in allogeneic
      recipients with low grades of immunogenicity. Implant geometry affects this
      phenomenon as osteoconduction appeared to augment the magnitude of the effects in
      larger tubular implants.

PMID- 24117845
TI  - Risk factors and clinical outcomes of gastric cancer identified by screening
      endoscopy: a case-control study.
AB  - BACKGROUND AND AIM: A customized screening program for gastric cancer would
      optimize the benefits of screening endoscopy. This study investigated the risk
      factors for gastric cancer detected during screening and factors affecting
      clinical outcomes. METHODS: From April 2000 to December 2010, subjects who
      underwent screening endoscopy at Asan Medical Center were included. To
      investigate risk factors, age- and sex-matched control group was selected. The
      clinical outcomes of gastric cancer identified during screening (screening group)
      were compared with age, sex, and date of diagnosis-matched subjects who were
      diagnosed with gastric cancer in the outpatient clinic (outpatient group).
      RESULTS: Of 109 530 subjects, 327 were diagnosed with gastric cancer. The median
      age of the screening group was 63.6 years (interquartile range 56-71 years), and
      the male-to-female ratio was 2.4:1. When comparing with the control group,
      Helicobacter pylori seropositivity (odds ratio [OR] 2.933, P < 0.001),
      carcinoembryonic antigen (OR 8.633, P = 0.004), family history of gastric cancer
      (OR 2.254, P = 0.007), and drinking (OR 3.312, P < 0.001) were independent
      positive risk factors, and the use of aspirin a negative risk factor for gastric
      cancer (OR 0.445, P = 0.012) in multivariate analysis. Low-density lipoprotein
      cholesterol (hazard ratio [HR] 0.987, P = 0.005), cancer antigen 19-9 (HR 21.713,
      P < 0.001), resectability (HR 59.833, P < 0.001), and family history (HR 0.308, P
      = 0.009) were independent risk factors for death. The 5-year survival rate was
      significantly higher in the screening group than in the outpatient group (P <
      0.001). CONCLUSIONS: Early detection of gastric cancer by screening endoscopy
      while asymptomatic enhances patient outcomes, especially in high-risk groups.

PMID- 24117846
TI  - Is more hair always better? A single biopsy specimen is preferred for the
      evaluation of alopecia.

PMID- 24117847
TI  - Biochemical criteria at 1 year are not robust indicators of response to
      ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year
      cohort study.
AB  - BACKGROUND: In primary biliary cirrhosis (PBC), biochemical criteria at 1 year
      are considered surrogates of response to ursodeoxycholic acid (UDCA). However,
      due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to
      assess the therapeutic response, particularly in early disease. AIM: To determine
      whether evaluation of biochemical criteria at 1 year is a reliable surrogate of
      UDCA response in early PBC. METHODS: We analysed the prospectively collected data
      of 215 patients (untreated = 129; UDCA-treated = 86) with early PBC (normal
      baseline bilirubin/albumin) and a median follow-up of 8 years (range: 1-29.1).
      The 1-year attainment rates of the Barcelona, Paris-I, Paris-II and Toronto
      definitions, and their predictive relevance for a poor outcome (death,
      transplantation, complications of cirrhosis), were assessed either as a result of
      UDCA or no treatment. Independent associations with attaining each UDCA response
      definition were identified by multivariate analysis. RESULTS: Untreated patients
      displayed 1-year biochemical features compatible with 'treatment response' at
      rates (Barcelona: 36.4%, Paris-I: 66.7%, Toronto: 59.7%, Paris-II: 40.3%) similar
      to those obtained under UDCA. Depending on the definition, baseline ALP<=3xULN
      (OR: 4.80-35.90), AST<=2xULN (OR: 5.63-9.34) and early histological stage (OR:
      3.67-3.87) were the stronger predictors for attaining the criteria. UDCA
      treatment was associated with attaining Barcelona (OR = 2.16) and Paris-II (OR =
      2.84), but not Paris-I, and not Toronto definition when excluding late
      histological cases. Paris-I criteria were significantly predictive of long-term
      outcomes (HR = 2.83) in untreated patients. CONCLUSIONS: In early PBC,
      biochemical criteria at 1 year reflect severity of the disease rather than the
      therapeutic response to UDCA.

PMID- 24117848
TI  - Synaptic activity bidirectionally regulates a novel sequence-specific S-Q
      phosphoproteome in neurons.
AB  - Protein phosphorylation plays a critical role in neuronal transcription,
      translation, cell viability, and synaptic plasticity. In neurons, phospho-enzymes
      and specific substrates directly link glutamate release and post-synaptic
      depolarization to these cellular functions; however, many of these enzymes and
      their protein substrates remain uncharacterized or unidentified. In this article,
      we identify a novel, synaptically driven neuronal phosphoproteome characterized
      by a specific motif of serine/threonine-glutamine ([S/T]-Q, abbreviated as SQ).
      These SQ-containing substrates are predominantly localized to dendrites,
      synapses, the soma; and activation of this SQ phosphoproteome by bicuculline
      application is induced via calcium influx through L-type calcium channels. On the
      other hand, acute application of NMDA can inactivate this SQ phosphoproteome. We
      demonstrate that the SQ motif kinase Ataxia-telangiectasia mutated can also
      localize to dendrites and dendritic spines, in addition to other subcellular
      compartments, and is activated by bicuculline application. Pharmacology studies
      indicate that Ataxia-telangiectasia mutated and its sister kinase ataxia
      telangiectasia mutated and Rad3-related up-regulate these neuronal SQ substrates.
      Phosphoproteomics identified over 150 SQ-containing substrates whose
      phosphorylation is bidirectionally regulated by synaptic activity.

PMID- 24117849
TI  - The effect of glutathione on 2-hydroxyethylmethacrylate cytotoxicity and on resin
      dentine bond strength.
AB  - AIM: To evaluate the influence of reduced glutathione (GSH) application on 2
      hydroxyethylmethacrylate (HEMA) cytotoxicity on rat pulpal cells and evaluate the
      effect of etched-dentine treatment with GSH on the immediate microtensile bond
      strength (MUTBS) of etch-and-rinse adhesive. METHODOLOGY: The cytotoxicity of 10
      mmol L(-1) HEMA, 10 mmol L(-1) HEMA + 1 mmol L(-1) GSH, 10 mmol L(-1) HEMA + 5
      mmol L(-1) GSH and 10 mmol L(-1) HEMA + 10 mmol L(-1) GSH was compared (6 h and
      24 h). Cells viability was measured by means of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, followed by morphological observation of
      cells. Etched-dentine surfaces were rinsed and treated with one of the following
      solutions: 2% GSH, 5% GSH or 10% GSH, bonded with Adper Single Bond Plus (3M,
      ESPE, St. Paul, MN, USA) and restored with resin composite. The control group
      received no GSH treatment. After 1 day of water-storage at 37  degrees C, the
      specimens were subjected to MUTBS testing. Cytotoxicity and MUTBS data were
      analysed by one-way anova and Tukey post hoc tests (P < 0.05). RESULTS: There
      were significant differences between the groups. HEMA elicited a remarkable toxic
      effect. 10 mmol L(-1) GSH prevented HEMA-induced damage at both exposure times.
      Whilst 5 mmol L(-1) GSH lost its protective effect at 24-h exposure time and 1
      mmol L(-1) GSH showed no protective effect at both exposure times, GSH had no
      significant effect on the immediate MUTBS; however, 5% GSH had higher bond
      strength value when compared to 10% GSH (P = 0.003). CONCLUSION: Controlled
      concentrations of GSH had a protective effect against HEMA cytotoxicity. GSH had
      neither positive nor negative influence on MUTBS.

PMID- 24117851
TI  - Adaptation to spring heat and drought in northeastern Spanish Arabidopsis
      thaliana.
AB  - The extent to which a species' environmental range reflects adaptive
      differentiation remains an open question. Environmental gradients can lead to
      adaptive divergence when differences in stressors among sites along the gradient
      place conflicting demands on the balance of stress responses. The extent to which
      this is accomplished through stress tolerance vs stress avoidance is also an open
      question. We present results from a controlled environment study of 48 lineages
      of Arabidopsis thaliana collected along a gradient in northeastern Spain across
      which temperatures increase and precipitation decreases with decreasing
      elevation. We tested the extent to which clinal adaptive divergence in heat and
      drought is explained through tolerance and avoidance traits by subjecting plants
      to a dynamic growth chamber cycle of increasing heat and drought stress analogous
      to low elevation spring in northeastern Spain. Lineages collected at low
      elevation were the most fit and fitness scaled with elevation of origin. Higher
      fitness was associated with earlier bolting, greater early allocation to
      increased numbers of inflorescences, reduction in rosette leaf photosynthesis and
      earlier fruit ripening. We propose that this is a syndrome of avoidance through
      early flowering accompanied by restructuring of the organism that adapts A.
      thaliana to low-elevation Mediterranean climates.

PMID- 24117850
TI  - A conserved sequence in calmodulin regulated spectrin-associated protein 1 links
      its interaction with spectrin and calmodulin to neurite outgrowth.
AB  - Calmodulin regulated spectrin-associated protein 1 (CAMSAP1) is a vertebrate
      microtubule-binding protein, and a representative of a family of cytoskeletal
      proteins that arose with animals. We reported previously that the central region
      of the protein, which contains no recognized functional domain, inhibited neurite
      outgrowth when over-expressed in PC12 cells [Baines et al., Mol. Biol. Evol. 26
      (2009), p. 2005]. The CKK domain (DUF1781) binds microtubules and defines the
      CAMSAP/ssp4 family of animal proteins (Baines et al. 2009). In the central
      region, three short well-conserved regions are characteristic of CAMSAP-family
      members. One of these, CAMSAP-conserved region 1 (CC1), bound to both
      betaIISigma1-spectrin and Ca(2+)/calmodulin in vitro. The binding of
      Ca(2+)/calmodulin inhibited spectrin binding. Transient expression of CC1 in PC12
      cells inhibited neurite outgrowth. siRNA knockdown of CAMSAP1 inhibited neurite
      outgrowth in PC12 cells or primary cerebellar granule cells: this could be
      rescued in PC12 cells by wild-type CAMSAP1-enhanced green fluorescent protein,
      but not by a CC1 mutant. We conclude that CC1 represents a functional region of
      CAMSAP1, which links spectrin-binding to neurite outgrowth.

PMID- 24117852
TI  - Diverse profiles of N-acyl-homoserine lactone molecules found in cnidarians.
AB  - Many marine habitats, such as the surface and tissues of marine invertebrates,
      including corals, harbour diverse populations of microorganisms, which are
      thought to play a role in the health of their hosts and influence mutualistic and
      competitive interactions. Investigating the presence and stability of quorum
      sensing (QS) in these ecosystems may shed light on the roles and control of these
      bacterial communities. Samples of 13 cnidarian species were screened for the
      presence and diversity of N-acyl-homoserine lactones (AHLs; a prevalent type of
      QS molecule) using thin-layer chromatography and an Agrobacterium tumefaciens
      NTL4 biosensor. Ten of 13 were found to harbour species-specific, conserved AHL
      profiles. AHLs were confirmed in Anemonia viridis using liquid chromatography
      tandem mass spectrometry. To assess temporal role and stability, AHLs were
      investigated in A. viridis from intertidal pools over 16 h. Patterns of AHLs
      showed conserved profiles except for two mid-chain length AHLs, which increased
      significantly over the day, peaking at 20:00, but had no correlation with pool
      chemistry. Denaturing gel electrophoresis of RT-PCR-amplified bacterial 16S rRNA
      showed the presence of an active bacterial community that changed in composition
      alongside AHL profiles and contained a number of bands that affiliate with known
      AHL-producing bacteria. Investigations into the quorum sensing-controlled,
      species-specific roles of these bacterial communities and how these regulatory
      circuits are influenced by the coral host and members of the bacterial community
      are imperative to expand our knowledge of these interactions with respect to the
      maintenance of coral health. 

PMID- 24117853
TI  - Haemodynamic consequences of recurrent insulin-induced hypoglycaemia.
AB  - 1. Recurring insulin-induced hypoglycaemia (RIIH) often occurs during the
      therapeutic management of insulin-dependent diabetes mellitus. Controversy
      currently exists in the literature as to the ability of insulin and/or
      hypoglycaemia to promote hypertension. Could insulin and/or hypoglycaemia promote
      adverse pressor effects? If so, under what conditions and through what mechanism?
      Thus, the present study was performed to evaluate the hypothesis that RIIH
      produces hypertension via induction of heme oxygenase (HO)-1, promoting a
      significant increase in endogenous carbon monoxide (CO). 2. Male Sprague-Dawley
      rats were treated for 2 weeks with varying doses of insulin (1, 3, 5, 7 and 9
      U/kg, s.c.) or vehicle and fed normal rat chow or a zinc diet (1 mmol/L) for 2
      weeks. Tail-cuff blood pressure, food intake and blood glucose states were
      monitored daily. 3. A dose-dependent decrease in blood glucose was observed in
      insulin-treated rats. Blood pressure was significantly elevated in rats treated
      with 9 and 7 U/kg insulin compared with those treated with other doses of
      insulin. However, there was no change in urine output among the groups. Feeding
      of a high-zinc diet to rats treated with 7 U/kg insulin and treatment with the HO
      1 inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 20 mg/kg) after insulin
      injection resulted in a significant reduction in blood pressure compared with 7
      U/kg insulin injection alone. In addition, HO-1 protein levels in the heart and
      kidney and endogenous CO levels were reduced in 7 U/kg insulin-treated rats fed
      the high-zinc diet compared with those treated with the same dose of insulin
      alone. 4. The results of the present study demonstrate that RIIH promotes
      hypertension and that restoration of normal CO levels with a high-zinc diet and
      ZnDPBG reduces blood pressure.

PMID- 24117854
TI  - Annual research review: A developmental psychopathology approach to understanding
      callous-unemotional traits in children and adolescents with serious conduct
      problems.
AB  - Recent research has suggested that the presence of significant levels of callous
      unemotional (CU) traits designates a clinically important and etiologically
      distinct subgroup of children and adolescents with serious conduct problems.
      Based on this research, CU traits have been included in the most recent revision
      of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5;
      American Psychiatric Association, 2013)--as a specifier for the diagnosis of
      conduct disorder. In this review, we attempt to understand CU traits within a
      developmental psychopathological framework. Specifically, we summarize research
      on the normal development of the prosocial emotions of empathy and guilt (i.e.,
      conscience) and we illustrate how the development of CU traits can be viewed as
      the normal development of conscience gone awry. Furthermore, we review research
      on the stability of CU traits across different developmental periods and
      highlight factors that can influence this stability. Finally, we highlight the
      implications of this developmental psychopathological framework for future
      etiological research, for assessment and diagnostic classification, and for
      treatment of children with serious conduct problems.

PMID- 24117855
TI  - Characterization of the complications associated with plasma exchange for
      thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic
      anaemias: a single institution experience.
AB  - BACKGROUND: Plasma exchange (PEX) is a life-saving therapeutic procedure in
      patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic
      microangiopathic anaemias (TMAs). However, it may be associated with significant
      complications, exacerbating the morbidity and mortality in this patient group.
      STUDY DESIGN AND METHODS: We reviewed all PEX procedures over a 72-month period,
      following the exclusive introduction of solvent-detergent double viral
      inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK).
      We documented allergic reactions to plasma, citrate reactions, complications
      relating to central venous access insertion and venous thrombotic events (VTE) in
      155 patient episodes and >2000 PEX procedures. RESULTS: The overall complication
      rate was low. Allergic plasma reactions occurred in 6.45% of the cohort with only
      one episode of acute anaphylaxis. Similarly, VTEs were 6.45%, not significantly
      greater than in medical patients receiving thromboprophylaxis, despite added
      potential risk factors in TTP. Citrate reactions were the most frequent
      complication documented, but toxicity was significantly reduced by administration
      of further calcium infusions during the PEX procedure. There were no serious
      central line infections and no catheter thrombosis. CONCLUSION: Our data confirms
      that PEX continues to be a life-saving procedure in the acute TTP setting and,
      the procedure was not associated with an increased mortality and limited
      morbidity.

PMID- 24117856
TI  - Quality of life and functional capacity after long-term right ventricular pacing
      in pediatrics and young adults with congenital atrioventricular block.
AB  - BACKGROUND: Although several studies have demonstrated deleterious consequences
      of chronic right ventricular (RV) pacing on ventricular function and
      synchronicity, its effects on health-related quality of life (HRQoL) and
      functional exercise capacity remain uncertain. We aimed to evaluate the effect of
      RV pacing on HRQoL and functional capacity of children and young adults with
      congenital complete atrioventricular block (CCAVB). METHODS: We included 66
      consecutive subjects with RV cardiac pacemaker due to CCAVB and under clinical
      follow-up for more than 1 year. Multidimensional HRQoL scores were evaluated by
      Short Form-36 Health Survey (SF-36) and Child Health Questionnaire-Parent Form 50
      (CHQ-PF50). Functional capacity was tested by a 6-minute walk distance test
      (6MWDT). Association analysis was performed to examine if any demographic and
      clinical characteristics were associated with lower HRQoL scores and shorter
      distances at the 6MWDT. RESULTS: Domains presenting lower HRQoL scores were
      vitality (64.0 +/- 17.3), mental health (67.3 +/- 8.0), role emotional (69.7 +/-
      35.8) in the SF-36 questionnaire; general health perceptions (61.3 +/- 8.3),
      general behavior (61.9 +/- 15.6), parental impact-emotional (67.7 +/- 28.7) in
      the CHQ-PF50. Female gender (P = 0.009), left ventricular ejection fraction lower
      than 55% (P = 0.013), cardiovascular drugs (P = 0.003) were significantly
      associated with lower HRQoL scores. Average distance traveled during the 6MWDT
      was 539.8 +/- 82.9 m. The 6MWDT showed significant association with age (P =
      0.006) and cardiovascular drugs (P = 0.024). CONCLUSIONS: Chronic RV pacing did
      not affect the HRQoL and physical capacity of pediatrics and young subjects.
      Female gender, ventricular function, and cardiovascular drugs were associated
      with lower HRQoL scores. Older subjects walked shorter distances in the 6MWDT, as
      well as subjects who were taking cardiovascular drugs.

PMID- 24117857
TI  - Motivational interviewing improves exclusive breastfeeding in an Australian
      randomised controlled trial.
AB  - AIM: To increase maintenance of breastfeeding through improved primary care
      support. METHOD: A cluster randomised controlled trial recruited 15 rural family
      doctor's offices and 330 women who were currently breastfeeding took part. Eight
      practices formed the intervention group (154 women) and seven formed the control
      group (176 women). The practice nurses who provided the intervention used a
      specially designed motivational flowchart to speak to the mothers when they
      brought their child for immunisation at 2, 4 and 6 months. The nurses also
      attended preparatory workshops on breastfeeding management, counselling skills,
      motivational interviewing and reflective practice and were given resources and
      support. Breastfeeding rates were measured at 4 and 6 months. RESULTS:
      Randomisation equally distributed all measured variables except prenatal
      intentions to rejoin employment within 12 months (70% intervention, 56% control,
      p < 0.05). After adjustment, the 4-month figures showed significantly higher
      rates of exclusive breastfeeding (OR 1.88; 95%CI 1.01-3.50; p = 0.047) and full
      breastfeeding (water/juice allowed) (OR 1.95; 95%CI 1.03-3.69; p = 0.04) in the
      intervention group. There were no differences at 6 months. CONCLUSION: A
      motivational interviewing intervention by primary care health professionals who
      have undertaken a replicable training programme is feasible and effective in
      increasing exclusive breastfeeding and full/predominant breastfeeding at 4
      months.

PMID- 24117858
TI  - Different antigenicities of the N-terminal region of cellular and scrapie prion
      proteins.
AB  - Limited information is available about conformational differences between the
      abnormal isoform of prion protein (PrP(Sc) ) and cellular prion protein (PrP(C) )
      under native conditions. To clarify conformational differences between these two
      isoforms, PrP-deficient mice were immunized with brain homogenates of normal and
      scrapie-infected animals. All mice generated anti-PrP antibodies. Peptide array
      analysis of these serum samples revealed a distinctive epitope of PrP(Sc)
      consisting of QGSPGGN (PrP41-47) at the N-terminus. This study demonstrated a
      conformational dissimilarity at the N-terminus between PrP(Sc) and PrP(C) , a
      finding that may provide novel information about conformational features of
      PrP(Sc) . 

PMID- 24117859
TI  - Neuroendocrine differentiation correlates with hormone receptor expression and
      decreased survival in patients with invasive breast carcinoma.
AB  - AIMS: Invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation
      has been controversial in terms of its definition and clinical outcome. We
      investigated the incidence and clinical significance of NE differentiation in
      patients with IBC. METHODS AND RESULTS: We performed immunohistochemistry for NE
      markers, chromogranin-A and synaptophysin on 1428 IBC samples using tissue
      microarrays and classified cases with NE differentiation into two groups, focal
      (1-49% tumour cells positive for any NE marker) and diffuse (>=50% tumour cells
      positive) groups. Fifty-nine cases (4.1%) showed NE differentiation
      immunohistochemically, and the majority did not show typical NE morphology. The
      presence of NE differentiation showed a significant association with positive
      oestrogen receptor (P = 0.001) and progesterone receptor (P = 0.008) status.
      Patients with NE differentiation showed worse overall survival (OS) and disease
      free survival (DFS) than those without NE differentiation in both univariate (P <
      0.001 for both) and multivariate (OS, P = 0.004; DFS, P < 0.001) analyses.
      CONCLUSIONS: IBC with NE differentiation is a distinct subtype of mammary
      carcinoma with an aggressive clinical outcome.

PMID- 24117860
TI  - Development of a validated exam to assess physician transfusion medicine
      knowledge.
AB  - BACKGROUND: There is evidence that physicians lack adequate transfusion medicine
      knowledge. To design needs-based educational interventions to address this gap, a
      validated assessment tool is required. Previously published exams have not been
      created or validated using rigorous psychometric methods. STUDY DESIGN AND
      METHODS: A modified Delphi method was used to achieve consensus regarding the
      essential knowledge and skills for physicians who transfuse blood products. To
      ensure content validity, members of an international organization of transfusion
      medicine experts (Biomedical Excellence for Safer Transfusion [BEST]
      Collaborative) participated in the exam design process. An exam, based on the
      most highly rated topics, was created and administered to individuals with a
      priori expected basic, intermediate, and expert levels of transfusion medicine
      knowledge. Rasch analysis, a psychometric technique used in high-stakes medical
      licensure and board testing, was used to determine exam accuracy and precision.
      RESULTS: Thirty-six topics achieved ratings sufficient to be considered for
      inclusion in the exam (content validity index > 0.8). A 23-question exam was
      administered to 49 individuals. Mean scores for individuals with expected basic,
      intermediate, and expert knowledge were 42, 62, and 82%, respectively (p <
      0.0001). The exam achieved good fit with the Rasch model. CONCLUSION: A validated
      exam has now been created to accurately assess transfusion medicine knowledge.
      This exam can be used to determine knowledge deficits and assist in the design of
      curricula to improve blood product utilization.

PMID- 24117862
TI  - The pharmacokinetics and safety profiles of belimumab after single subcutaneous
      and intravenous doses in healthy Japanese volunteers.
AB  - WHAT IS KNOWN AND OBJECTIVES: Belimumab is a recombinant human monoclonal
      antibody that binds and antagonizes the biological activity of soluble B
      lymphocyte stimulator (BLyS) protein. BLyS appears to play a role in the
      pathogenesis of systemic lupus erythematosus, and the biological profile of
      belimumab suggests that it may have a therapeutic benefit in the treatment for
      the disease. In this healthy Japanese subjects study, we investigated the
      pharmacokinetics and safety of a single subcutaneous and intravenous injection of
      belimumab administered as a 200 mg/mL liquid formulation. METHODS: This was an
      open-label, randomized, parallel-group, single-dose study in healthy Japanese
      subjects. Each subject received a single intravenous infusion or a subcutaneous
      injection of 200 mg belimumab. The pharmacokinetic parameters and safety
      parameters including local tolerance (injection site), biomarkers, immunogenicity
      and adverse events were evaluated up to 70 days post-dosing. RESULTS: After a
      single intravenous or a subcutaneous administration of 200 mg belimumab, all 16
      subjects completed the study. There were no serious adverse events or adverse
      events related to injection site reactions. All seven adverse events were
      considered mild or moderate in intensity and deemed unrelated to belimumab except
      for cellulitis following intravenous administration. The bioavailability of the
      single subcutaneous dose of 200 mg belimumab in the subjects was estimated to be
      77.5%. Time to the maximum serum concentration after subcutaneous injection was
      6.5 days (median). The geometric mean terminal half-life was comparable between
      the two administration routes (17.7 days intravenous and 15.9 days subcutaneous).
      Serum immunoglobulin G level decreased slightly after each treatment. No subjects
      were found to produce antibelimumab antibodies. WHAT IS NEW AND CONCLUSIONS: A
      favourable absolute bioavailability in healthy Japanese subjects was seen
      following a subcutaneous injection of 200 mg belimumab. Considering the
      intersubject variability, exposures were consistent with those previously
      observed in healthy non-Japanese subjects. Safety and biomarker data were also
      consistent with previous non-Japanese clinical studies.

PMID- 24117864
TI  - Melatonin enhances the recovery of cryopreserved shoot tips of American elm
      (Ulmus americana L.).
AB  - Climate change and global migrations of people and goods have exposed trees to
      new diseases and abiotic challenges that threaten the survival of species. In
      vitro germplasm storage via cryopreservation is an effective tool to ensure
      conservation of tree species, but plant cells and tissues are exposed to multiple
      stresses during the cryopreservation process. The current study was designed to
      evaluate the potential of melatonin to improve survival through the process of
      cryopreservation. Shoot tips of in vitro-grown plantlets and dormant winter buds
      of American elm were successfully cryopreserved in liquid nitrogen (LN) at -196
      degrees C under controlled environmental conditions following melatonin treatment
      and cold acclimation with either vitrification or encapsulation-vitrification
      protocols. Explants had optimal regrowth following cryopreservation when treated
      with the plant vitrification solution#2 (PVS2) for 10 min. Supplementation of
      both preculture and regrowth media with melatonin significantly enhanced regrowth
      of frozen shoots compared with the untreated control (P < 0.05). Approximately 80
      100% of shoot explants grew under optimized conditions using melatonin-enriched
      media. Shoot tips of dormant winter buds consistently produced nearly 100%
      regrowth with both techniques. The main steps of the optimized protocol are14-day
      cold-acclimated cultures exposed to preculture medium with 0.1-0.5 lM melatonin
      for 24 hr, application of PVS2 for 10 min, rapid cooling in LN, rapid rewarming,
      removal of cryoprotectants, and recovery on a medium supplemented with 0.1-0.5 lM
      melatonin. Our results demonstrate the usefulness of the antioxidant melatonin
      for long-term storage of naturally resistant elm germplasm.

PMID- 24117861
TI  - IgE-based immunotherapy of cancer: challenges and chances.
AB  - Passive immunotherapy with monoclonal antibodies is an indispensable cornerstone
      of clinical oncology. Notably, all FDA-approved antibodies comprise the IgG
      class, although numerous research articles proposed monoclonal antibodies of the
      IgM, IgG, IgA and IgE classes directed specifically against tumor-associated
      antigens. In particular, for the IgE isotype class, several recent studies could
      demonstrate high tumoricidic efficacy. Therefore, this review specifically
      highlights the latest developments toward IgE-based immunotherapy of cancer.
      Possible mechanisms and safety aspects of IgE-mediated tumor cell death are
      discussed with special focus on the attracted immune cells. An outlook is given
      on how especially comparative oncology could contribute to further developments.
      Humans and dogs have a highly comparable IgE biology, suggesting that
      translational AllergoOncology studies in patients with canine cancer could have
      predictive value for the potential of IgE-based anticancer immunotherapy in human
      clinical oncology. 

PMID- 24117865
TI  - Expectations and self-efficacy of African American parents who discuss sexuality
      with their adolescent sons: an intervention study.
AB  - OBJECTIVE: Despite research that suggests parental communication may help deter
      high-risk sexual behavior among adolescents, parents report a lack of confidence
      in their ability to answer sexually related questions. The purpose of this study
      was to test the effect of a multimedia intervention on outcome expectations and
      perceived self-efficacy for the sex educator role for parents of African American
      adolescent males. DESIGN AND SAMPLE: A pilot study using mixed methods was
      conducted. A nonprobability sample (N = 61) was obtained from a large urban
      community using a combination of convenience and snowball recruitment methods.
      MEASURES: Self-efficacy and outcome expectations were measured using self
      reported questionnaires. INTERVENTION: A multimedia intervention for use at home
      and incorporating an audio CD and associated activities was implemented over a 3
      week time period. RESULTS: Outcome expectations and self-efficacy both
      significantly improved after the intervention (p < .001). CONCLUSIONS: Findings
      indicate that using a multimedia approach may be effective in improving parents'
      outcome expectancy and self-efficacy for talking about sex with adolescent sons.

PMID- 24117863
TI  - Molecular mechanism of ERK dephosphorylation by striatal-enriched protein
      tyrosine phosphatase.
AB  - Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of
      neuronal synaptic plasticity, and its abnormal level or activity contributes to
      cognitive disorders. One crucial downstream effector and direct substrate of STEP
      is extracellular signal-regulated protein kinase (ERK), which has important
      functions in spine stabilisation and action potential transmission. The
      inhibition of STEP activity toward phospho-ERK has the potential to treat
      neuronal diseases, but the detailed mechanism underlying the dephosphorylation of
      phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward
      para-nitrophenyl phosphate, phospho-tyrosine-containing peptides, and the full
      length phospho-ERK protein using STEP mutants with different structural features.
      STEP was found to be a highly efficient ERK tyrosine phosphatase that required
      both its N-terminal regulatory region and key residues in its active site.
      Specifically, both kinase interaction motif (KIM) and kinase-specific sequence of
      STEP were required for ERK interaction. In addition to the N-terminal kinase
      specific sequence region, S245, hydrophobic residues L249/L251, and basic
      residues R242/R243 located in the KIM region were important in controlling STEP
      activity toward phospho-ERK. Further kinetic experiments revealed subtle
      structural differences between STEP and HePTP that affected the interactions of
      their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho
      ERK peptide sequence through its active site, and the contact of STEP F311 with
      phospho-ERK V205 and T207 were crucial interactions. Taken together, our results
      not only provide the information for interactions between ERK and STEP, but will
      also help in the development of specific strategies to target STEP-ERK
      recognition, which could serve as a potential therapy for neurological disorders.
      Regulation of phospho-ERK by STEP underlies important neuronal activities. A
      detailed enzymologic characterisation and cellular studies of STEP revealed that
      specific residues in KIM and active site mediated ERK recognition. Structural
      differences between the KIM-ERK interfaces and the active site among different
      ERK phosphatases could be targeted to develop specific STEP inhibitor, which has
      therapeutic potential for neurological disorders. PKA, protein kinase A & NGF,
      nerve growth factor.

PMID- 24117866
TI  - Photogrammetric documentation of regions of interest at autopsy--a pilot study.
AB  - In this pilot study, the authors tested whether photogrammetry can replace or
      supplement physical measurements made during autopsies and, based on such
      measurements, whether virtual computer models may be applicable in forensic
      reconstructions. Photogrammetric and physical measurements of markers denoting
      wounds on five volunteers were compared. Virtual models of the volunteers were
      made, and the precision of the markers' locations on the models was tested.
      Twelve of 13 mean differences between photogrammetric and physical measurements
      were below 1 cm, which indicates that the photogrammetric method has a high
      accuracy. The precision of the markers' location on the models was somewhat less,
      although the method is still promising and potentially superior to the current
      procedures used for reconstructions. The possibility to measure any distance on a
      body, even after the autopsy is concluded and the corpse is no longer available,
      is one of the biggest benefits of photogrammetry.

PMID- 24117867
TI  - Hepatic involvement in paediatric patients with paracoccidioidomycosis: a
      histological study.
AB  - AIM: Paracoccidioidomycosis is a systemic mycosis that is endemic to certain
      countries in Latin America. This study aimed to describe the histological
      features of liver involvement in patients with paracoccidioidomycosis aged <16
      years of age who were treated between 1980 and 2010, with a diagnosis that was
      confirmed by detection of the fungus by pathological examination. METHODS AND
      RESULTS: Liver tissue was obtained from one necropsy and 12 biopsies. Throughout
      2007, biopsies were taken from patients with persistent jaundice or portal
      hypertension, after which biopsies became indicated due to elevated
      aminotransferase and low albumin levels. Using haematoxylin and eosin (H&E),
      Masson's trichrome and immunohistochemical (CK7 and CK19) staining, we noted
      degenerative alterations in bile duct cells and inflammatory injury to the bile
      ducts in 10 biopsies. Using immunohistochemistry for CK7 and CK19, we observed
      ductal proliferation in all 12 samples. CONCLUSIONS: Bile duct injuries by
      inflammatory cells might explain the predominant increase in canalicular enzymes;
      immunohistochemistry is more sensitive in demonstrating ductular reactions and
      might show changes that are not apparent on H&E staining.

PMID- 24117868
TI  - The pepper cysteine/histidine-rich DC1 domain protein CaDC1 binds both RNA and
      DNA and is required for plant cell death and defense response.
AB  - Plant defense against microbial pathogens is coordinated by a complex regulatory
      network. Cysteine/histidine-rich DC1 domain proteins mediate a variety of
      cellular processes involved in plant growth, development and stress responses. We
      identified a pepper (Capsicum annuum) cysteine/histidine-rich DC1 domain protein
      gene, CaDC1, which positively regulates plant defense during microbial infection,
      based on gene silencing and transient expression in pepper, as well as ectopic
      expression in Arabidopsis. Induction of CaDC1 by avirulent Xanthomonas campestris
      pv vesicatoria (Xcv) infection was pronounced at both transcriptional and
      translational levels in pepper leaves. Purified CaDC1 protein bound to both DNA
      and RNA in vitro, especially in the presence of Zn(2+). CaDC1 was localized to
      both the nucleus and the cytoplasm, which was required for plant cell death
      signaling. The nuclear localization of CaDC1 was dependent on the divergent C1
      (DC1) domain. CaDC1 silencing in pepper conferred increased susceptibility to Xcv
      infection, which was accompanied by reduced salicylic acid accumulation and
      defense-related gene expression. Ectopic expression of CaDC1 in Arabidopsis
      enhanced resistance to Hyaloperonospora arabidopsidis. CaDC1 binds both RNA and
      DNA and functions as a positive regulator of plant cell death and SA-dependent
      defense responses.

PMID- 24117870
TI  - Classic dose-response and time postinoculation models for leptospira.
AB  - Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas,
      and prevalent in both industrialized and rural settings. Dose-response models
      were generated from 22 data sets reported in 10 different studies. All of the
      selected studies used rodent subjects, primarily hamsters, with the predominant
      endpoint as mortality with the challenge strain administered intraperitoneally.
      Dose-response models based on a single evaluation postinfection displayed median
      lethal dose (LD50 ) estimates that ranged between 1 and 10(7) leptospirae
      depending upon the strain's virulence and the period elapsed since the initial
      exposure inoculation. Twelve of the 22 data sets measured the number of affected
      subjects daily over an extended period, so dose-response models with time
      dependent parameters were estimated. Pooling between data sets produced seven
      common dose-response models and one time-dependent model. These pooled common
      models had data sets with different test subject hosts, and between disparate
      leptospiral strains tested on identical hosts. Comparative modeling was done with
      parallel tests to test the effects of a single different variable of either
      strain or test host and quantify the difference by calculating a dose
      multiplication factor. Statistical pooling implies that the mechanistic processes
      of leptospirosis can be represented by the same dose-response model for different
      experimental infection tests even though they may involve different host species,
      routes, and leptospiral strains, although the cause of this pathophysiological
      phenomenon has not yet been identified. 

PMID- 24117869
TI  - Lipid profile and atherogenic indices soon after birth in Japanese preterm
      infants.
AB  - AIM: The intra-uterine environment affects the risk of development of
      cardiovascular disease in adulthood. The aim of this study was to determine the
      influence of prematurity and foetal growth restriction on lipid metabolism, by
      assessing atherogenic indices soon after birth in preterm infants. METHODS: Blood
      samples were collected within 20 min of birth from 80 preterm infants with a
      gestational age of <=35 weeks. Serum total cholesterol (TC), low-density
      lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc),
      apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured. The
      ratio of TC/HDLc, LDLc/HDLc and apoB/apoA1 were also calculated. Correlations
      between these indices and gestational age, birth weight and the standard
      deviation (SD) score for birth weight were also determined. RESULTS: Gestational
      age, birth weight and SD score for birth weight were negatively correlated with
      the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios. CONCLUSION: In preterm infants,
      prematurity and poor foetal growth may influence lipid and apolipoprotein
      metabolism and affect atherogenic indices at birth.

PMID- 24117871
TI  - Impact of parental-rearing styles on irritable bowel syndrome in adolescents: a
      school-based study.
AB  - BACKGROUND AND AIM: A strong association between family function and irritable
      bowel syndrome (IBS) has been observed. Parental rearing styles, as a
      comprehensive mark for family function, may provide new clues to the etiology of
      IBS. This study aimed to explore which dimensions of parental rearing styles were
      risk factors or protective factors for IBS in adolescents. METHODS: Two thousand
      three hundred twenty adolescents were recruited from one middle school and one
      high school randomly selected from Jiangan District (an urban district in Wuhan
      City). Data were collected using two Chinese versions of validated self-report
      questionnaires including the Rome III diagnostic criteria for pediatric IBS and
      the Egna Minnen Betraffande Uppfostran: One's Memories of Upbringing for
      perceived parental rearing styles. RESULTS: Ninety-six subjects diagnosed as
      pediatric IBS were compared with 1618 controls. The IBS patients reported less
      both paternal and maternal emotional warmth (all P < 0.01) and more both paternal
      and maternal punishment, overinterference, rejection, and overprotection (only
      for father) (all P < 0.01) than the controls. Furthermore, the IBS patients had
      higher total scores of parental rearing styles (all P < 0.001) than the controls.
      With univariate logistic regression, standardized regression coefficients and
      odds ratios of parental rearing variables were calculated. Multivariate logistic
      regression revealed that paternal rejection (P = 0.001) and maternal
      overinterference (P = 0.002) were independent risk factors for IBS in
      adolescents. CONCLUSIONS: Parental emotional warmth is a protective factor for
      IBS in adolescents and parental punishment, overinterference, rejection, and
      overprotection are risk factors for IBS in adolescents.

PMID- 24117872
TI  - Postantibiotic effect and postantibiotic sub-minimum inhibitory concentration
      effect of valnemulin against Staphylococcus aureus isolates from swine and
      chickens.
AB  - The postantibiotic effect (PAE) and postantibiotic sub-minimum inhibitory
      concentration (MIC) effect (PA-SME) of valnemulin against Staphylococcus aureus
      were investigated in vitro using a spectrophotometric technique and classic
      viable count method. A standard curve was constructed by regression analysis of
      the number of colonies and the corresponding optical density (OD) at 630 nm of
      the inoculum. After exposure to valnemulin at different concentrations for an
      hour, the antibiotic was removed by centrifuging and washing. The PA-SMEs were
      measured after initial exposure to valnemulin at 4 * the MIC, and then,
      valnemulin was added to reach corresponding desired concentrations in the
      resuspended culture. Samples were collected hourly until the culture became
      turbid. The results were calculated by converting the OD values into the counts
      of bacteria in accordance with the curve. The MIC of valnemulin against eight
      strains was identically 0.125 MUg ml(-1) . The mean PAEs were 2.12 h (1 * MIC)
      and 5.06 h (4 * MIC), and the mean PA-SMEs were 6.85 h (0.1 * MIC), 9.12 h (0.2 *
      MIC) and 10.8 h (0.3 * MIC). The results showed that the strains with identical
      MICs exhibited different PAEs and PA-SMEs. Valnemulin produced prolonged PAE and
      PA-SME periods for Staph. aureus, supporting a longer dosing interval while
      formulating a daily administration dosage. SIGNIFICANCE AND IMPACT OF THE STUDY:
      In this study, valnemulin demonstrated prolonged postantibiotic effects and
      postantibiotic sub-MIC effects on strains of Staphylococcus aureus. The strains
      with identical MICs of valnemulin exhibited different PAEs and PA-SMEs.
      Staphylococcus aureus isolated from different species has little impact on the
      postantibiotic effect of valnemulin. The result suggests a longer dosing interval
      while formulating a daily administration dosage, and it may play a valuable role
      of valnemulin in treating Staph. aureus infections in animals.

PMID- 24117873
TI  - Atrial flutter or fibrillation is the most frequent and life-threatening
      arrhythmia in myotonic dystrophy.
AB  - BACKGROUND: Several arrhythmias were reported in myotonic dystrophy (MD).
      OBJECTIVES: To evaluate the prevalence of atrial fibrillation (AF) and atrial
      flutter (AFL) in MD and the clinical consequences. METHODS: One hundred sixty-one
      patients, mean age 41 +/- 14 years, were referred for a type 1 MD. All patients
      were asymptomatic except four patients and followed during 5 +/- 4 years.
      Electrocardiogram (ECG), echocardiography assessing left ventricular ejection
      fraction, and Holter monitoring were obtained and repeated. RESULTS: Twenty-seven
      patients (17%) presented sustained (>1 hour) AF (n = 15) or AFL (n = 12); two of
      them presented syncope-related 1/1 AFL. In one of them, 16 years of age, cardiac
      defibrillator was implanted for a diagnosis of ventricular tachycardia, but the
      true diagnosis was established after inappropriate shocks. AFL ablation was
      performed in five patients, but four developed AF. The other seven patients with
      AFL developed AF. During the follow-up, 22 patients died (14%) from cardiac and
      respiratory failure; eight patients with AF/AFL died (30%) while only 14 without
      AF/AFL died (10%; P < 0.01). Univariate analysis indicated that age >40 years
      (death: 48 +/- 14 vs 40 +/- 8 in alive patients), abnormal ECG, and occurrence of
      AF/AFL were significant factors of death. At multivariate analysis, AF at ECG
      (odds ratio: 3.12) and age >40 (odds ratio: 3.14) were the sole independent
      variables predicting death. CONCLUSIONS: AF and AFL were frequent in MD and
      increased mortality. AFL could present as 1/1 AFL with a poor tolerance and a
      risk of misdiagnosis despite frequent conduction disturbances. This arrhythmia
      could explain wide QRS tachycardia occurring in MD and interpreted as VT.

PMID- 24117874
TI  - Practitioner review: Social (pragmatic) communication disorder conceptualization,
      evidence and clinical implications.
AB  - BACKGROUND: DSM-5 sees the introduction of Social (Pragmatic) Communication
      Disorder (SPCD), characterized by persistent difficulties using verbal and
      nonverbal communication for social purposes, in the absence of restricted and
      repetitive interests and behaviours. There is currently much confusion about the
      precise diagnostic criteria for SPCD and how this disorder relates to autism
      spectrum disorders (ASD), previous descriptions of pragmatic language impairment
      (PLI) and more specific language disorders (LD). METHOD: Proposed criteria for
      SPCD are outlined. A selective review of the evidence considers whether these
      criteria form a cohesive and distinct diagnostic entity. Approaches to assessment
      and intervention are discussed. RESULTS: Implementing the new diagnosis is
      currently challenged by a lack of well-validated and reliable assessment
      measures, and observed continuities between SPCD and other neurodevelopmental
      disorders. High rates of comorbidity between SPCD and other seemingly disparate
      disorders (including conduct disorder, ADHD and disorders of known genetic
      origin) raise questions about the utility of this diagnostic category.
      CONCLUSIONS: SPCD is probably best conceptualized as a dimensional symptom
      profile that may be present across a range of neurodevelopmental disorders,
      although there is an urgent need to investigate the latent structure of SPCD
      using consistent diagnostic criteria. In addition, social communication and
      aspects of pragmatic language may be dissociated, with the latter heavily
      influenced by structural language attainments. Finally, there is a dearth of
      reliable and culturally valid assessment measures with which to make a
      differential diagnosis, and few rigorously tested intervention programmes. The
      implications for research and clinical practice are outlined.

PMID- 24117875
TI  - Improved protective efficacy of a chimeric Staphylococcus aureus vaccine
      candidate iron-regulated surface determinant B ( N 126- P 361) -target of RNAIII
      activating protein in mice.
AB  - The pathogen Staphylococcus aureus causes a wide range of serious infections,
      necessitating urgent development of a vaccine against this organism. However,
      currently developed vaccines are relatively ineffective because of the limited
      antigenic component that is contained in the vaccine formulations. To develop an
      effective S. aureus candidate vaccine, overlapping PCR was used to add the
      truncated immunodominant antigen iron-regulated surface determinant B (IsdB)(N126
      P361) (tIsdB) to the N-terminal of intact antigen target of RNAIII activating
      protein (TRAP) and thus construct a tIsdB-TRAP chimera. The humoral and cellular
      immune responses against tIsdB-TRAP were compared with those against single or
      combined formulations. tIsdB-TRAP elicited significantly stronger humoral
      responses in mice (P < 0.05). As to cellular immune responses in mice, the tIsdB
      TRAP group resulted in a greater IL-4 response than did other groups (P < 0.05).
      Greater amounts of IL-2 and IFN-gamma were found in the tIsdB-TRAP group. Mouse
      challenge also showed that tIsdB-TRAP provided better protection against S.
      aureus than did the control groups. These results suggest that this chimeric
      protein may be a promising pathogen target for further vaccine development. 

PMID- 24117876
TI  - Nicorandil improves electrical remodelling, leading to the prevention of
      electrically induced ventricular tachyarrhythmia in a mouse model of desmin
      related cardiomyopathy.
AB  - 1. Transgenic (TG) mice overexpressing an arg120gly missense mutation in heat
      shock protein B5 (HSPB5; i.e. R120G TG mice) exhibit desmin-related
      cardiomyopathy. Recently, the cardioprotective effect of nicorandil has been
      shown to prolong the survival of R120G TG mice. However, whether the TG mice
      exhibit ventricular arrhythmias and whether nicorandil can inhibit these
      arrhythmias remain unknown. In the present study we examined the effects of
      chronic nicorandil administration on ventricular electrical remodelling and
      arrhythmias in R120G TG mice. 2. Mice were administered nicorandil (15 mg/kg per
      day) or vehicle (water) orally from 5 to 30 weeks of age. Electrocardiograms
      (ECG) and optical action potentials were recorded from R120G TG mouse hearts. In
      addition, the expression of ventricular connexin 43 and the cardiac Na(+) channel
      Nav1.5 was examined in TG mice. 3. All ECG parameters tested were prolonged in
      R120G TG compared with non-transgenic (NTG) mice. Nicorandil improved the
      prolonged P, PQ and QRS intervals in R120G TG mice. Interestingly, impulse
      conduction slowing and increases in the expression of total and phosphorylated
      connexin 43 and Nav1.5 were observed in ventricles from R120G TG compared with
      NTG mice. Nicorandil improved ventricular impulse conduction slowing and
      normalized the increased protein expression levels of total and phosphorylated
      connexin 43, but not of Nav1.5, in R120G TG mouse hearts. Electrical rapid pacing
      at the ventricle induced ventricular tachyarrhythmias (VT) in six of eight R120G
      TG mouse hearts, but not in any of the eight nicorandil-treated R120G TG mouse
      hearts (P < 0.05). 4. These findings demonstrate that nicorandil inhibits cardiac
      electrical remodelling and that the prevention of VT by nicorandil is associated
      with normalization of connexin 43 expression in this model.

PMID- 24117877
TI  - Loss of membranous expression of the intracellular domain of EpCAM is a frequent
      event and predicts poor survival in patients with pancreatic cancer.
AB  - AIMS: Epithelial cell adhesion molecule (EpCAM) is a widely used
      immunohistochemical marker for epithelial human malignancies. Antibodies to
      target EpCAM are usually directed against its ectodomain (EpEX), but do not
      detect the intracellular domain (EpICD). The aim of this study was to compare
      membranous EpEX versus EpICD expression by immunohistochemistry. METHODS AND
      RESULTS: Concurrent EpEX and EpICD expression was investigated retrospectively in
      cancerous and matched non-neoplastic tissue samples from patients with pancreatic
      adenocarcinoma. In total, 317 paired samples of pancreatic tissue from 88
      patients were analysed and correlated with clinicopathological parameters. In non
      cancerous tissue, a high concordance of membranous EpEX and EpICD expression was
      observed and defined as the expression of the full-length EpCAM (EpEX(+)/EpICD(+)
      phenotype, EpCAM(MF)), which was highly predominant. In contrast, while most
      tumour samples were EpEX positive, loss of membranous EpICD expression
      (EpEX(+)/EpICD(-) phenotype, EpCAM(MT)) was observed in one-third of cases, and
      these patients had a significantly shortened disease-free and overall survival.
      CONCLUSIONS: This study demonstrates for the first time that loss of membranous
      EpICD expression is a frequent event and predicts poor prognosis in patients with
      pancreatic cancer. Additional studies evaluating the predictive and prognostic
      value of the expression of different membranous EpCAM variants are warranted in
      epithelial cancers.

PMID- 24117878
TI  - Two rare variants of keratoacanthoma in the same sign-out session.

PMID- 24117879
TI  - Analysis of the recovery of cryopreserved and thawed CD34+ and CD3+ cells
      collected for hematopoietic transplantation.
AB  - BACKGROUND: Cryopreservation is often used to store cellular therapies, but
      little is known about how well CD3+ or CD34+ cells tolerate this process. STUDY
      DESIGN AND METHODS: Viable CD34+ cell recoveries were analyzed from related and
      unrelated donor granulocyte-colony-stimulating factor (G-CSF)-mobilized
      peripheral blood stem cell (PBSC) products and viable CD3+ cell recoveries from G
      CSF-mobilized and nonmobilized apheresis products from related and unrelated
      donors. All products were cryopreserved with 5% dimethyl sulfoxide and 6%
      pentastarch using a controlled-rate freezer and were stored in liquid nitrogen.
      Related donor products were cryopreserved immediately after collection and
      unrelated donor products greater than 12 hours postcollection. RESULTS: The
      postthaw recovery of CD34+ cells from related donor PBSCs was high (n = 86; 97.5
      +/- 23.1%) and there was no difference in postthaw CD34+ cell recovery from
      unrelated donor PBSCs (n = 14; 98.8 +/- 37.2%; p = 0.863). In related donor
      lymphocyte products the postthaw CD3+ cell recovery (n = 48; 90.7 +/- 21.4%) was
      greater than that of unrelated donor products (n = 14; 66.6 +/- 35.8%; p =
      0.00251). All unrelated donor lymphocyte products were from G-CSF-mobilized
      products, while most related donor lymphocyte products were from nonmobilized
      products. A comparison of the CD3+ cell recovery from related donor G-CSF
      mobilized products (n = 19; 85.0 +/- 29.2%) with that of unrelated donor products
      found no significant difference (p = 0.137). CONCLUSIONS: The postthaw recovery
      of CD34+ cells was high in both related and unrelated donor products, but the
      recovery of CD3+ cells in unrelated donor G-CSF-mobilized products was lower. G
      CSF-mobilized unrelated donor products may contain fewer CD3+ cells than non-G
      CSF-exposed products upon thaw and, when indicated, cell doses should be
      monitored.

PMID- 24117881
TI  - Biofilm removal by 6% sodium hypochlorite activated by different irrigation
      techniques.
AB  - AIM: To compare the removal of biofilm utilizing four irrigation techniques on a
      bovine root canal model. METHODOLOGY: Fifty dentine specimens (2 * 2 mm) were
      infected with biofilm. The samples were then adapted to previously created
      cavities in the bovine model. The root canals were irrigated twice with 2 mL of
      6% sodium hypochlorite for 2 min (4 min total). Following initial irrigation, the
      different treatment modalities were introduced for 60 s (3 * 20 s intervals). The
      evaluated techniques were needle irrigation, Endoactivator (Dentsply Tulsa
      Dental, Tulsa, OK, USA), passive ultrasonic irrigation and laser-activated
      irrigation (photon-induced photoacoustic streaming). The controls were irrigated
      with distilled water and conventional needle irrigation. Subsequently, the
      dentine samples were separated from the model and analysed using a scanning
      electron microscope (SEM). Fifteen operative fields were scanned per block, and
      SEM pictures were captured. Two calibrated evaluators examined the images and
      collected data using a four-degree scale. Nonparametric tests were used to
      evaluate for statistical significance amongst the groups. RESULTS: The group
      undergoing laser-activated irrigation using photon-induced photoacoustic
      streaming exhibited the most favourable results in the removal of biofilm.
      Passive ultrasonic irrigation scores were significantly lower than both the
      Endoactivator and needle irrigation scores. Sonic and needle irrigation were not
      significantly different. The least favourable results were found in the control
      group. CONCLUSIONS: Laser activation of 6% sodium hypochlorite significantly
      improved the cleaning of biofilm-infected dentine followed by passive ultrasonic
      irrigation.

PMID- 24117880
TI  - Simvastatin inhibits lipopolysaccharide-induced osteoclastogenesis and reduces
      alveolar bone loss in experimental periodontal disease.
AB  - BACKGROUND AND OBJECTIVE: Statins are inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase and have anti-inflammatory effects independent of
      cholesterol lowering. Recent clinical studies have indicated that statin intake
      has a beneficial effect on periodontal disease. However, the underlying
      mechanisms have not been well understood. In the current study, we employed a rat
      model with lipopolysaccharide (LPS)-induced periodontal disease and determined
      the effect of simvastatin, a commonly prescribed statin, on osteoclastogenesis,
      gingival inflammation and alveolar bone loss. MATERIAL AND METHODS: Sprague
      Dawley rats were injected with Aggregatibacter actinomycetemcomitans LPS in
      periodontal tissue three times per week for 8 wk and part of the rats with LPS
      injection were also given simvastatin via gavage. After the treatments, the rat
      maxillae were scanned by microcomputed tomography and the images were analyzed to
      determine alveolar bone loss. To explore the underlying mechanisms, the effect of
      simvastatin on osteoclastogenesis and gingival expression of proinflammatory
      cytokines were also determined by tartrate-resistant acid phosphatase staining
      and real-time polymerase chain reaction assays, respectively. RESULTS: Results
      showed that LPS treatment markedly increased bone loss, but administration of
      simvastatin significantly alleviated the bone loss. Results also showed that LPS
      treatment stimulated osteoclastogenesis and the expression of inflammatory
      cytokines, but simvastatin significantly modulates the stimulatory effect of LPS
      on osteoclastogenesis and cytokine expression. CONCLUSION: This study
      demonstrated that simvastatin treatment inhibits LPS-induced osteoclastogenesis
      and gingival inflammation and reduces alveolar bone loss, indicating that the
      intake of simvastatin may hinder the progression of periodontal disease.

PMID- 24117882
TI  - Staphylococcus aureus enterotoxin-specific IgE is associated with asthma in the
      general population: a GA(2)LEN study.
AB  - BACKGROUND: Specific IgE to Staphylococcus aureus enterotoxins (SE-IgE) has been
      associated with asthma. In the general population, we aimed to determine the
      prevalence of and risk factors for serum SE-IgE and to examine the association
      with asthma. METHODS: A postal questionnaire was sent to a random sample of
      adults in 19 centers across Europe. A random sample of respondents was invited
      for clinical examination upon which they answered a questionnaire, underwent skin
      prick tests (SPTs) for common aeroallergens, and provided blood for measurement
      of total IgE and SE-IgE. Risks were analyzed within centers using weighted
      logistic regression, and overall estimates calculated using fixed-effects meta
      analysis. RESULTS: 2908 subjects were included in this analysis. Prevalence of
      positive SE-IgE was 29.3%; no significant geographic variation was observed. In
      contrast to positive skin prick tests, SE-IgE was more common in smokers (<15
      pack-year: OR 1.11, P = 0.079, >=15 pack-year: OR 1.70, P < 0.001), and
      prevalence did not decrease in older age-groups or in those with many siblings.
      Total IgE concentrations were higher in those with positive SE-IgE than in those
      with positive SPT. SE-IgE was associated with asthma (OR 2.10, 95% confidence
      interval [1.60-2.76], P = 0.001) in a concentration-dependent manner. This effect
      was independent of SPT result and homogeneous across all centers. CONCLUSIONS: We
      report for the first time that SE-IgE is common in the general population
      throughout Europe and that its risk factors differ from those of IgE against
      aeroallergens. This is the first study to show that SE-IgE is significantly and
      independently associated with asthma in the general population.

PMID- 24117883
TI  - Blood donation by African migrants and refugees in Australia: the role of
      demographic and socio-economic factors.
AB  - BACKGROUND AND OBJECTIVES: To establish blood donation rates among African
      refugees and migrants and identify demographic and socio-economic factors that
      are associated with their blood donation. MATERIALS AND METHODS: A cross
      sectional survey of 425 migrants and refugees living in Victoria and South
      Australia was used to assess blood donation status. The association between blood
      donation and demographic and socio-economic factors was assessed using multiple
      logistic regression analysis. RESULTS: Overall, 73 participants (17.2%; 95% CI:
      13.6-20.8) reported having donated blood previously. Of the total sample, 2.4%
      (95% CI: 0.9-3.8) reported having given blood in Australia; 12.9% (95% CI: 9.7
      16.1) had given blood prior to migration to Australia (i.e. country of birth or
      transition); and 1.9% (95% CI: 0.6-3.2) indicated they had given blood in an
      unspecified country. In the univariate model, age, country of birth, blood
      donation knowledge, religion, educational attainment, migration and employment
      status were all associated with blood donation status. However, in the
      multivariate model, only age >45 years (odds ratio [OR] 5.72; 95% CI 2.11-15.46),
      African region of origin (OR 15.89; 95% CI 3.89-65) and blood donation knowledge
      (OR 4.46; 95% CI 1.57-12.7) were associated with blood donation. CONCLUSIONS: In
      order to increase the number of blood donors among African migrants, promoting
      knowledge and awareness of issues associated with blood donation in Australia
      should be emphasized. Consideration should be given to identifying these
      potential migrant donors to improve the availability of compatible blood for
      patients of African descent.

PMID- 24117884
TI  - GSTP1 is a hub gene for gene-air pollution interactions on childhood asthma.
AB  - There is growing evidence that multiple genes and air pollutants are associated
      with asthma. By identifying the effect of air pollution on the general
      population, the effects of air pollution on childhood asthma can be better
      understood. We conducted the Taiwan Children Health Study (TCHS) to investigate
      the influence of gene-air pollution interactions on childhood asthma. Complete
      monitoring data for the ambient air pollutants were collected from Taiwan
      Environmental Protection Agency air monitoring stations. Our results show a
      significant two-way gene-air pollution interaction between glutathione S
      transferase P (GSTP1) and PM10 on the risk of childhood asthma. Interactions
      between GSTP1 and different types of air pollutants have a higher information
      gain than other gene-air pollutant combinations. Our study suggests that
      interaction between GSTP1 and PM10 is the most influential gene-air pollution
      interaction model on childhood asthma. The different types of air pollution
      combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It
      implies that GSTP1 is an important hub gene in the anti-oxidative pathway that
      buffers the harmful effects of air pollution. 

PMID- 24117885
TI  - Effects of chocolate on cognitive function and mood: a systematic review.
AB  - A systematic review was conducted to evaluate whether chocolate or its
      constituents were capable of influencing cognitive function and/or mood. Studies
      investigating potentially psychoactive fractions of chocolate were also included.
      Eight studies (in six articles) met the inclusion criteria for assessment of
      chocolate or its components on mood, of which five showed either an improvement
      in mood state or an attenuation of negative mood. Regarding cognitive function,
      eight studies (in six articles) met the criteria for inclusion, of which three
      revealed clear evidence of cognitive enhancement (following cocoa flavanols and
      methylxanthine). Two studies failed to demonstrate behavioral benefits but did
      identify significant alterations in brain activation patterns. It is unclear
      whether the effects of chocolate on mood are due to the orosensory
      characteristics of chocolate or to the pharmacological actions of chocolate
      constituents. Two studies have reported acute cognitive effects of
      supplementation with cocoa polyphenols. Further exploration of the effect of
      chocolate on cognitive facilitation is recommended, along with substantiation of
      functional brain changes associated with the components of cocoa.

PMID- 24117886
TI  - Novel integrons and gene cassettes from a Cascadian submarine gas-hydrate-bearing
      core.
AB  - To determine whether integrons are present in a submarine gas hydrate community,
      metagenomic DNA was extracted from a gas-hydrate-bearing core, 150 m below the
      seafloor, from the Cascadian Margin. Integrons and gene cassettes were recovered
      by PCR from metagenomic DNA and sequenced. Thirty-seven integron integrase
      phylotypes were identified. The phylotypes were diverse and included members with
      homology to integrases from Methylomonas methanica, Desulfuromonas acetoxidans,
      Thermodesulfatator indicus, and marine uncultured bacteria. The gene cassette
      composition, 153 gene cassettes, was dominated by two types of encoded putative
      proteins. The first of these was predicted oxidoreductases, such as iron/sulfur
      cluster-binding proteins. A second type was alkyl transferases. Some cassette
      proteins showed homologies with those from methane-related archaea. These
      observations suggest that integrons may assist in the adaptation of microbial
      communities in this environment. 

PMID- 24117887
TI  - Biomechanical evaluation of the stabilizing function of the atlantoaxial
      ligaments under shear loading: a canine cadaveric study.
AB  - OBJECTIVES: To evaluate the stabilizing function of atlanto-axial ligaments in
      dogs. STUDY DESIGN: Cadaveric biomechanical study. ANIMALS: Beagle dog cadavers
      (n = 10). METHODS: The craniocervical region was collected from 10 Beagle
      cadavers, and the occipito-atlanto-axial region was prepared and freed from the
      surrounding muscles. Care was taken to preserve integrity of the atlantoaxial
      ligaments and atlantoaxial joint capsule. The atlanto-occipital joints were
      blocked with 2 diverging transarticular 1.8 mm positive threaded K-wires.
      Specimen extremities were embedded in polymethylmethacrylate (PMMA) and mounted
      on a simulator testing shear load at the atlantoaxial joint. Range of motion
      (ROM) and neutral zone (NZ) were determined with all ligaments intact, after
      cutting the apical ligament, both alar ligaments, the transverse ligaments and
      finally after cutting the dorsal atlantoaxial ligament. RESULTS: ROM increased
      similarly and stepwise during testing. The most significant increase was observed
      after transection of the alar ligaments. CONCLUSION: The alar ligaments seem to
      be the most important ligamentous structures for stabilization of the
      atlantoaxial joint under shear load.

PMID- 24117888
TI  - Maternal infections during pregnancy and cerebral palsy: a population-based
      cohort study.
AB  - BACKGROUND: Cerebral palsy (CP) is a common motor disability in childhood. We
      examined the association between maternal infections during pregnancy and the
      risk of congenital CP in the child. METHODS: Liveborn singletons in Denmark
      between 1997 and 2003 were identified from the Danish National Birth Registry and
      followed from 1 year of life until 2008. Redemption of antibiotics from the
      National Register of Medicinal Product Statistics and maternal infections
      reported by the National Hospital Register were used as markers of maternal
      infection during pregnancy. CP diagnoses were obtained from the Danish Cerebral
      Palsy Registry. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were
      estimated by Cox proportional hazard models. RESULTS: Of the 440 564 singletons
      with follow-up data, 840 were diagnosed with congenital CP. Maternal genito
      urinary tract infections (HR 2.1, 95% CI 1.4, 3.2) were associated with CP in all
      births, in term births (HR 1.9, 95% CI 1.1, 3.2), in children with spastic CP (HR
      2.1, 95% CI 1.4, 3.3), and among first-born children (HR 1.9, 95% CI 1.4, 3.3).
      Overall, we found associations between redeemed nitrofurantoin (HR 1.7, 95% CI
      1.1, 2.8) and CP. Among trimester-specific exposures, CP risk was associated with
      prescriptions redeemed in the first trimester for any antibacterials, beta-lactam
      antibacterials, and nitrofurantoin, an antibiotic commonly used to treat lower
      urinary tract infection, and genito-urinary tract infections in the third
      trimester. CONCLUSION: Genito-urinary tract infections and antibiotic use during
      pregnancy were associated with increased risks of CP, indicating that some
      maternal infections or causes of maternal infections present in prenatal life may
      be part of a causal pathway leading to CP.

PMID- 24117889
TI  - CaMKII represses transcriptionally active beta-catenin to mediate acute ethanol
      neurodegeneration and can phosphorylate beta-catenin.
AB  - Prenatal ethanol exposure causes persistent neurodevelopmental deficits by
      inducing apoptosis within neuronal progenitors including the neural crest. The
      cellular signaling events underlying this apoptosis are unclear. Using an
      established chick embryo model, we previously identified ethanol's activation of
      calmodulin-dependent protein kinase II (CaMKII) as a crucial early step in this
      pathway. Here, we report that CaMKII is pro-apoptotic because it mediates the
      loss of transcriptionally active beta-catenin, which normally provides trophic
      support to these cells. beta-catenin over-expression normalized cell survival in
      ethanol's presence. CaMKII inhibition similarly restored beta-catenin content and
      transcriptional activity within ethanol-treated cells and prevented their cell
      death. In contrast, inhibition of alternative effectors known to destabilize beta
      catenin, including glycogen synthase kinase-3beta, Protein Kinase C, JNK, and
      calpain, failed to normalize cell survival and beta-catenin activity in ethanol's
      presence. Importantly, we found that purified CaMKII can directly phosphorylate
      beta-catenin. Using targeted mutagenesis we identified CaMKII phosphorylation
      sites within human beta-catenin at T332, T472, and S552. This is the first
      demonstration that beta-catenin is a phosphorylation target of CaMKII and
      represents a novel mechanism by which calcium signals could regulate beta-catenin
      dependent transcription. These results inform ethanol's neurotoxicity and offer
      unexpected insights into other neurodevelopmental and neurodegenerative disorders
      having dysregulated calcium or beta-catenin signaling.

PMID- 24117890
TI  - Reconstructing relative genome size of vascular plants through geological time.
AB  - The strong positive relationship evident between cell and genome size in both
      animals and plants forms the basis of using the size of stomatal guard cells as a
      proxy to track changes in plant genome size through geological time. We report
      for the first time a taxonomic fine-scale investigation into changes in stomatal
      guard-cell length and use these data to infer changes in genome size through the
      evolutionary history of land plants. Our data suggest that many of the earliest
      land plants had exceptionally large genome sizes and that a predicted overall
      trend of increasing genome size within individual lineages through geological
      time is not supported. However, maximum genome size steadily increases from the
      Mississippian (c. 360 million yr ago (Ma)) to the present. We hypothesise that
      the functional relationship between stomatal size, genome size and atmospheric
      CO2 may contribute to the dichotomy reported between preferential extinction of
      neopolyploids and the prevalence of palaeopolyploidy observed in DNA sequence
      data of extant vascular plants.

PMID- 24117891
TI  - A qualitative descriptive study of risk reduction for coronary disease among the
      Hong Kong Chinese.
AB  - OBJECTIVES: Achieving optimal control and reduction in coronary heart disease
      (CHD) risks in Hong Kong (HK) remains significant and requires exploring. This
      article addresses the ability to reduce CHD risks among the HK Chinese. DESIGN
      AND SAMPLE: Through secondary analysis, a qualitative descriptive design using
      focus group interviews and content analysis were adopted. Older and younger
      adults were invited for the study. MEASURES: An interview schedule was used to
      guide discussions during focus group interviews. RESULTS: Four categories emerged
      from the data: planning of health actions, control of risk-reducing behavior,
      perceived opportunities for understanding CHD, and chest pain appraisal.
      CONCLUSIONS: Local culture and population needs play a central role in disease
      perception and prevention. The findings are essential to target strategies for
      initiating health acts for younger adults and establish public education
      resources that underscore understanding of CHD risk, symptom recognition, and
      disease management, particularly among those middle-aged and older people at high
      risk and with the diseased populations.

PMID- 24117892
TI  - Greasy roads: the impact of bad financial news on road traffic accidents.
AB  - We use evidence from a natural experiment in Greece to study the effect of the
      announcement of austerity measures on road traffic accidents (RTAs). We use daily
      RTA data from 2010 and 2011, during which a number of austerity measures were
      announced, including salary and pension cuts and an increase in direct and
      indirect taxes. We find that controlling for other factors potentially
      influencing RTAs, the number of RTAs increased significantly on the first two
      days following the announcements of austerity measures. We put forward some
      tentative suggestions for why this happens. 

PMID- 24117893
TI  - Melanosis coli can involve adenomatous polyps.

PMID- 24117894
TI  - Callous-unemotional traits in children and mechanisms of impaired eye contact
      during expressions of love: a treatment target?
AB  - BACKGROUND: We previously hypothesised that the early development of psychopathy
      is associated with a failure to attend to the eyes of attachment figures, and we
      have presented preliminary data from a parent-child 'love' scenario in support of
      this. Here, we confirm the association in a larger sample and test mechanisms of
      impaired eye contact during expressions of love in control and behaviourally
      disturbed children. METHODS: Oppositional defiant disorder children, assessed for
      callous-unemotional (CU) traits, and controls, were observed in a brief
      interaction task where the mother was asked to show love to her child. Eye
      contact and affection were measured for each dyad. RESULTS: As predicted, there
      were no group differences in affection and eye contact expressed by mothers;
      levels of CU traits predicted low levels of eye contact towards their mothers
      across all groups of children. As expected, low eye contact was correlated with
      psychopathic fearlessness in their fathers, and maternal reports of negative
      feelings towards the child. Independent observations showed that child's
      behaviour largely drives the low eye contact associated with CU traits, and low
      eye contact was not associated with independent observations of the quality of
      attachment-related behaviours in mothers. CONCLUSIONS: Impaired eye contact is a
      unique characteristic of children with CU traits; these impairments are largely
      independent of maternal behaviour, but associated with psychopathic traits in the
      fathers. These impairments should be tested for functional significance and
      amenability to change in longitudinal and treatment studies.

PMID- 24117895
TI  - Ketamine is a neurotoxic agent that could adversely affect the brains of preterm
      babies.

PMID- 24117896
TI  - Antilisterial activity of lactose monolaurate in milk, drinkable yogurt and
      cottage cheese.
AB  - Lactose monolaurate (LML) was previously found to be an antimicrobial against
      Listeria monocytogenes in culture medium at concentrations between 3 and 5 mg ml(
      1) . In this study, the microbial inhibitory activity of LML in dairy products
      inoculated with a 5-strain cocktail of clinical isolates of L. monocytogenes was
      investigated. Addition of LML at a concentration of 5 mg ml(-1) resulted in 4.4,
      4.0 and 4.2 log reductions in 0.5% fat, 1% fat and 3.25% fat milks, respectively;
      4.1, 4.4, and 3.5 log reductions in nonfat, 1% fat, and 1.5% fat yogurts,
      respectively; and 4.0 log reductions in both nonfat and 2% fat cottage cheese.
      The inhibitory effect of LML was only observed at 37 degrees C and not 5 degrees
      C. Experiments suggest that both the lauric acid and the esterified lactose
      moiety of LML play roles in the growth inhibition. SIGNIFICANCE AND IMPACT OF THE
      STUDY: A novel sugar ester, lactose monolaurate, inhibited the growth of a five
      strain cocktail of Listeria monocytogenes in milk, yogurt and cottage cheese.
      This is the first report of the use of a sugar ester to inhibit the growth of
      Listeria in food systems.

PMID- 24117897
TI  - Effects of treatment with hydrogen sulfide on methionine-choline deficient diet
      induced non-alcoholic steatohepatitis in rats.
AB  - BACKGROUND AND AIM: Oxidative stress and inflammation play important roles in the
      progression from simple fatty liver to non-alcoholic steatohepatitis (NASH). The
      aim of this work was to investigate whether treatment with hydrogen sulfide (H2
      S) prevented NASH in rats through abating oxidative stress and suppressing
      inflammation. METHODS: A methionine-choline-deficient (MCD) diet rat model was
      prepared. Rats were divided into three experimental groups and fed for 8 weeks as
      follows: (i) control rats; (ii) MCD-diet-fed rats; (iii) MCD-diet-fed rats
      treated with NaHS (intraperitoneal injection of 0.1 mL/kg/day of 0.28 mol/L NaHS,
      a donor of H2 S). RESULTS: MCD diet impaired hepatic H2 S biosynthesis in rats.
      Treatment with H2 S prevented MCD-diet-induced NASH, as evidenced by hematoxylin
      and eosin staining, reduced apoptosis and activities of alanine aminotransferase
      and aspartate aminotransferase, and attenuated hepatic fat accumulation in rats.
      Treatment with H2 S abated MCD-diet-induced oxidative stress through reducing
      cytochrome p4502E1 expression, enhancing heme oxygenase-1 expression, and
      suppressing mitochondrial reactive oxygen species formation, and suppressed MCD
      diet-induced inflammation through suppressing activated nuclear factor kappaB
      signaling and reducing interleukin-6 and tumor necrosis factor alpha expressions.
      In addition, treatment of MCD-diet fed rats with H2 S had a beneficial modulation
      on expression profiles of fatty acid metabolism genes in livers. CONCLUSIONS:
      Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through
      abating oxidative stress and suppressing inflammation.

PMID- 24117898
TI  - Unexpected resilience to experimental gingivitis of subepithelial connective
      tissue grafts in gingival recession defects: a clinical-molecular evaluation.
AB  - BACKGROUND AND OBJECTIVE: The subepithelial connective tissue graft (SCTG) is the
      most widely used procedure for the treatment of gingival recession defects.
      Little is known, however, as to whether the apposed gingival flaps are more
      predisposed to develop plaque-related inflammation compared to healthy sites.
      This has salient clinical implications, as the long-term results of root coverage
      will depend largely on the level of inflammation of the grafted tissue. METHODS:
      In the present split-mouth case-control study, clinical and biomolecular
      parameters were used to assess the level of inflammation of periodontal sites 12
      mo after treatment with SCTG (test) and healthy non-treated gingivae (control)
      following the induction of plaque-related gingivitis in 19 patients. RESULTS: The
      data showed that test sites had a significantly (P < 0.05) lower gingival index
      and angulated bleeding score compared to control sites (gingival index = 1.05 +/-
      0.23 vs. 1.34 +/- 0.47; angulated bleeding score = 0.34 +/- 0.37 vs. 0.61 +/-
      0.39) after induction of experimental gingivitis, whereas the plaque index did
      not differ in the two groups (P > 0.05). With regard to the biomolecular
      parameters, baseline levels of the proinflammatory cytokine interleukin-1beta
      were higher in the gingival crevicular fluid of test sites. However, control
      sites exhibited more pronounced increase in the levels of interleukin-1beta
      compared to test sites, upon plaque accumulation, so that the final concentration
      was similar in both groups. No changes were recorded in the gingival crevicular
      fluid volume. CONCLUSION: Analysis of the data demonstrates that the sites of
      gingival recession treated with SCTG develop a lower degree of plaque-induced
      inflammation compared to healthy gingivae. This strongly suggests that SCTG does
      not predispose to inflammation and to further gingival recession and makes it a
      safe technique in the treatment of gingival defects.

PMID- 24117899
TI  - Partial engraftment following plerixafor rescue after failed sibling donor
      peripheral blood stem cell harvest.
AB  - BACKGROUND: Rarely, healthy donors fail adequate peripheral blood stem cell
      (PBSC) mobilization. If the recipient has already received conditioning
      chemotherapy, this can result in the donor undergoing urgent marrow harvest under
      general anesthesia. Plerixafor is a novel CXCR4 antagonist, licensed for
      autologous PBSC harvest (PBSCH) in patients who failed mobilization with
      granulocyte-colony-stimulating factor (G-CSF) alone. Experience using plerixafor
      in healthy allogeneic donors failing G-CSF mobilization is scarce. CASE REPORT: A
      65-year-old patient was referred for a reduced-intensity conditioning sibling
      allograft for relapsed follicular lymphoma. She received fludarabine, melphalan,
      and alemtuzumab conditioning. Her 68-year-old brother was fully HLA matched.
      PBSCH was planned on Day -1 after 4 days of 10 MUg/kg G-CSF. Day 1 PBSCH
      collected an inadequate number of CD34+ 0.35 * 10(6) /kg cells. Despite
      increasing G-CSF (16 MUg/kg), Day 2 yielded 0.33 * 10(6) /kg CD34+ cells, giving
      a suboptimal total dose. He proceeded to a third PBSCH day after plerixafor (0.24
      mg/kg) and G-CSF (16 MUg/kg) were given the evening before. A total of 1.79 *
      10(6) /kg CD34+ cells were harvested, giving a total dose of 2.46 * 10(6) /kg
      CD34+ cells. After initial neutrophil engraftment on Day +13, the patient's
      neutrophils gradually decreased to 0.02 * 10(9) /L by Day +74. A marrow aspirate
      on Day +81 was markedly hypocellular. Total white blood cell chimerism was near
      100% donor on Days +32, +74, and +102. Despite chimeric-only engraftment, the
      patient remains platelet and red blood cell transfusion dependent. CONCLUSION:
      Rescue plerixafor to assist PBSCH in healthy allogeneic donors has been effective
      in terms of CD34+ cell number mobilized. It is unclear whether the partial
      engraftment seen was coincidental or related to a difference in PBSC quality.

PMID- 24117900
TI  - Venous invasion in oesophageal adenocarcinoma: enhanced detection using elastic
      stain and association with adverse histological features and clinical outcomes.
AB  - AIMS: In oesophageal adenocarcinoma, detection rates of venous invasion using
      haematoxylin and eosin (H&E) and elastic stains have not been compared. The aims
      of this study were to investigate whether or not elastic stains facilitate the
      detection of venous invasion, and to determine the prognostic significance of
      venous invasion following review with elastic stains. METHODS AND RESULTS: One
      hundred and three resection specimens containing oesophageal adenocarcinoma, all
      reported originally as negative for venous invasion, were examined for the
      presence of venous invasion using H&E and subsequently Movat pentachrome stains.
      Venous invasion was detected in eight cases with H&E and an additional 66 cases
      using Movat pentachrome; overall, 72% of cases contained venous invasion. Venous
      invasion was associated with advanced stage, tumour size, lymphatic and
      perineural invasion and subsequent distant metastases. Venous invasion, stage,
      size, grade, lymphatic invasion and perineural invasion were prognostically
      significant on univariate analysis. Only tumour stage was independently
      prognostic. Two of eight patients with venous invasion but no other indication
      for adjuvant treatment died of recurrent disease. CONCLUSIONS: Elastic stains
      improve detection of venous invasion significantly in oesophageal adenocarcinoma.
      Venous invasion is associated with multiple adverse clinicopathological features.
      Its identification may facilitate the stratification of patients at risk for
      visceral metastases and disease-related death.

PMID- 24117901
TI  - Triplex real-time polymerase chain reaction assay for detection and
      quantification of norovirus (GI and GII) and sapovirus.
AB  - To improve detection of norovirus (NoVGI, NoVGII) and sapovirus (SaV), a
      simultaneous quantitative RT-PCR method was established. This triplex real-time
      PCR method was evaluated using a combination of optimized specific primers and
      probes. The performance of the developed PCR assay was equivalent to that of
      monoplex real-time PCR across a broad dynamic range of 10(2) -10(7) copies/assay
      using plasmid DNA standards. The limit of detection was 10(2) copies/assay. The
      quantitative value was comparable with that of monoplex real-time PCR of stool
      samples. Our triplex real-time PCR is useful for detection of NoV and SaV
      infections. 

PMID- 24117902
TI  - Clear cell acanthoma with changes of eccrine syringofibroadenoma: reactive change
      or clue to etiology?
AB  - We observed two patients with solitary lesions showing features of clear cell
      acanthoma with underlying eccrine syringofibroadenoma-like changes. The
      pathogenesis of these entities has been debated since their original
      descriptions, with most recent literature suggesting that both may represent
      reactive phenomena rather than true neoplasms. Our observation prompted us to
      perform a retrospective review of clear cell acanthoma cases to determine the
      frequency of such associated eccrine syringofibroadenoma changes. Of 47 examined
      cases of clear cell acanthoma, 9 (19%) showed associated changes of eccrine
      syringofibroadenoma. Immunohistochemical evaluation performed on a subset of
      cases identified similar but slightly divergent differentiation patterns within
      the lesions. While epithelial membrane antigen and PAS expression were similar in
      both components (although slightly different in intensity), the regions
      resembling eccrine syringofibroadenoma displayed additional immunoreactivities,
      supporting the presence of two distinct components. We have found that the
      concurrence of clear cell acanthoma with syringofibroadenomatous changes is more
      frequent than generally appreciated and suggest that these entities may share
      derivation from the eccrine apparatus. 

PMID- 24117903
TI  - Melatonin enhances chondrogenic differentiation of human mesenchymal stem cells.
AB  - Intramembranous ossification and endochondral ossification are two ways through
      which bone formation and fracture healing occur. Accumulating amounts of evidence
      suggests that melatonin affects osteoblast differentiation, but little is known
      about the effects of melatonin on the process of chondrogenic differentiation. In
      this study, the effects of melatonin on human mesenchymal stem cells (MSCs)
      undergoing chondrogenic differentiation were investigated. Cells were induced
      along chondrogenic differentiation via high-density micromass culture in
      chondrogenic medium containing vehicle or 50 nm melatonin. Histological study and
      quantitative analysis of glycosaminoglycan (GAG) showed induced cartilage tissues
      to be larger and richer in GAG, collagen type II and collagen type X in the
      melatonin group than in the untreated controls. Real-time RT-PCR analysis
      demonstrated that melatonin treatment significantly up-regulated the expression
      of the genes involved in chondrogenic differentiation, including aggrecan (ACAN),
      collagen type II (COL2A1), collagen type X (COL10A1), SRY (sex-determining region
      Y)-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and the potent
      inducer of chondrogenic differentiation, bone morphogenetic protein 2 (BMP2). And
      the expression of melatonin membrane receptors (MT) MT1 and MT2 were detected in
      the chondrogenic-induced-MSCs by immunofluorescence staining. Luzindole, a
      melatonin receptor antagonist, was found to partially block the ability of
      melatonin to increase the size and GAG synthesis of the induced cartilage
      tissues, as well as to completely reverse the effect of melatonin on the gene
      expression of ACAN, COL2A1, COL10A1, SOX9 and BMP2 after 7 days of
      differentiation. These findings demonstrate that melatonin enhances chondrogenic
      differentiation of human MSCs at least partially through melatonin receptors. 

PMID- 24117904
TI  - Adenosine effect reinforced by dipyridamol: a better test to detect incomplete
      pulmonary vein isolation?

PMID- 24117905
TI  - Extracellular matrix-associated proteome changes during non-host resistance in
      citrus-Xanthomonas interactions.
AB  - Non-host resistance (NHR) is a most durable broad-spectrum resistance employed by
      the plants to restrict majority of pathogens. Plant extracellular matrix (ECM) is
      a critical defense barrier. Understanding ECM responses during interaction with
      non-host pathogen will provide insights into molecular events of NHR. In this
      study, the ECM-associated proteome was compared during interaction of citrus with
      pathogen Xanthomonas axonopodis pv. citri (Xac) and non-host pathogen Xanthomonas
      oryzae pv. oryzae (Xoo) at 8, 16, 24 and 48 h post inoculation. Comprehensive
      analysis of ECM-associated proteins was performed by extracting wall-bound and
      soluble ECM components using both destructive and non-destructive procedures. A
      total of 53 proteins was differentially expressed in citrus-Xanthomonas host and
      non-host interaction, out of which 44 were identified by mass spectrometry. The
      differentially expressed proteins were related to (1) defense-response (5
      pathogenesis-related proteins, 3 miraculin-like proteins (MIR, MIR1 and MIR2) and
      2 proteases); (2) enzymes of reactive oxygen species (ROS) metabolism [Cu/Zn
      superoxide dismutase (SOD), Fe-SOD, ascorbate peroxidase and 2-cysteine
      peroxiredoxin]; (3) signaling (lectin, curculin-like lectin and concanavalin A
      like lectin kinase); and (4) cell-wall modification (alpha-xylosidase, glucan 1,
      3 beta-glucosidase, xyloglucan endotransglucosylase/hydrolase). The decrease in
      ascorbate peroxidase and cysteine-peroxiredoxin could be involved in maintenance
      of ROS levels. Increase in defense, cell-wall remodeling and signaling proteins
      in citrus-Xoo interaction suggests an active involvement of ECM in execution of
      NHR. Partially compromised NHR in citrus against Xoo, upon Brefeldin A pre
      treatment supported the role of non-classical secretory proteins in this
      phenomenon. 

PMID- 24117906
TI  - The "Bestie di Satana" murders.
AB  - In recent years, satanic groups have been responsible for various types and
      degrees of crimes. We report the case of a number of murders committed in Italy
      by a group of young people calling themselves the "Bestie di Satana". Forensic
      psychiatric assessment of the members of a satanic sect charged with the crime
      revealed that all the young people had a fragile, immature personality, a very
      low level of education and were socially disadvantaged. The trial of the members
      of the "Bestie di Satana" sect was concluded with the verdict of deliberate
      murder, and all the members were given long jail sentences. This report should
      lead us to explore social and cultural responses to juvenile satanism,
      statistically shown to be a relatively rare phenomenon but with a high criminal
      potential. 

PMID- 24117907
TI  - Regulation of DNA methylation by ethanol induces tissue plasminogen activator
      expression in astrocytes.
AB  - Alcohol exposure affects neuronal plasticity in the adult and developing brain.
      Astrocytes play a major role in modulating neuronal plasticity and are a target
      of ethanol. Tissue plasminogen activator (tPA) is involved in modulating neuronal
      plasticity by degrading the extracellular matrix proteins including fibronectin
      and laminin and is up-regulated by ethanol in vivo. In this study we explored the
      hypothesis that ethanol affects DNA methylation in astrocytes thereby increasing
      expression and release of tPA. It was found that ethanol increased tPA mRNA
      levels, an effect mimicked by an inhibitor of DNA methyltransferase (DNMT)
      activity. Ethanol also increased tPA protein expression and release, and
      inhibited DNMT activity with a corresponding decrease in DNA methylation levels
      of the tPA promoter. Furthermore, it was observed that protein levels of DNMT3A,
      but not DNMT1, were reduced in astrocytes after ethanol exposure. These novel
      studies show that ethanol inhibits DNA methylation in astrocytes leading to
      increased tPA expression and release; this effect may be involved in astrocyte
      mediated inhibition of neuronal plasticity by alcohol.

PMID- 24117909
TI  - No pain, no gain: depressed clients' experiences of cognitive behavioural
      therapy.
AB  - OBJECTIVES: Cognitive behavioural therapy (CBT) is an effective treatment for
      depression, but many clients do not complete therapy. What clients find difficult
      about CBT is poorly understood. This study explored clients' views and
      experiences of face-to-face CBT. DESIGN: A mixed methods design was used to
      collect data as part of the CoBalT trial. METHOD: Participants randomized to CBT
      indicated their reasons for never starting or stopping therapy on the follow-up
      questionnaires. In-depth qualitative interviews took place with a purposive
      sample (n = 26) of those randomized to CBT. Framework analysis was used to
      analyse across the data. RESULTS: Seventy-four participants withdrew from therapy
      or were discharged for non-adherence. A total of 54 (73%) gave reasons for not
      starting or stopping CBT; mostly the time/location was inconvenient or they had
      other commitments. Interviews identified that clients could struggle in, and
      between, CBT sessions. This was true for those who did and did not complete
      therapy. CBT homework was the biggest challenge and was often associated with
      negative school homework experiences. Although clients may have disliked aspects
      of CBT, those who attended more than one session felt that they had gained
      insight into managing their depression. CONCLUSION: Highlighting the possible
      barriers to adherence in CBT can help clinicians to better prepare clients in
      making an informed choice about therapy. Exploring these issues during therapy
      may also help with engagement. Despite the challenges, clients can still benefit
      from CBT by learning strategies that enable them to effectively deal with their
      depression.

PMID- 24117908
TI  - Effectiveness of pharmaceutical care for patients with chronic obstructive
      pulmonary disease (PHARMACOP): a randomized controlled trial.
AB  - AIMS: Few well-designed randomized controlled trials have been conducted
      regarding the impact of community pharmacist interventions on pharmacotherapeutic
      monitoring of patients with chronic obstructive pulmonary disease (COPD). We
      assessed the effectiveness of a pharmaceutical care programme for patients with
      COPD. METHODS: The pharmaceutical care for patients with COPD (PHARMACOP) trial
      is a single-blind 3 month randomized controlled trial, conducted in 170 community
      pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged
      >= 50 years and with a smoking history of >= 10 pack-years. A computer-generated
      randomization sequence allocated patients to an intervention group (n = 371),
      receiving protocol-defined pharmacist care, or a control group (n = 363),
      receiving usual pharmacist care (1:1 ratio, stratified by centre). Interventions
      focusing on inhalation technique and adherence to maintenance therapy were
      carried out at start of the trial and at 1 month follow-up. Primary outcomes were
      inhalation technique and medication adherence. Secondary outcomes were
      exacerbation rate, dyspnoea, COPD-specific and generic health status and smoking
      behaviour. RESULTS: From December 2010 to April 2011, 734 patients were enrolled.
      Forty-two patients (5.7%) were lost to follow-up. At the end of the trial,
      inhalation score [mean estimated difference (Delta),13.5%; 95% confidence
      interval (CI), 10.8-16.1; P < 0.0001] and medication adherence (Delta, 8.51%; 95%
      CI, 4.63-12.4; P < 0.0001) were significantly higher in the intervention group
      compared with the control group. In the intervention group, a significantly lower
      hospitalization rate was observed (9 vs. 35; rate ratio, 0.28; 95% CI, 0.12-0.64;
      P = 0.003). No other significant between-group differences were observed.
      CONCLUSIONS: Pragmatic pharmacist care programmes improve the pharmacotherapeutic
      regimen in patients with COPD and could reduce hospitalization rates.

PMID- 24117910
TI  - Social defeat and PTSD symptoms following trauma.
AB  - OBJECTIVES: Research indicates that constructs relevant to social rank predict a
      diagnosis of post-traumatic stress disorder (PTSD), including mental defeat,
      alienation, and shame. However, no studies have yet explored a social rank view
      explicitly. DESIGN: This was a community-based study carried out online. Analyses
      were both cross-sectional and longitudinal over 6 months. METHODS: Participants
      were recruited online for a cross-sectional study (Study 1, n = 194) and a 6
      month longitudinal study (Study 2, n = 81). Measures included self-report
      measures of PTSD symptoms (the Post-Traumatic Diagnostic Scale) and social rank
      (including measures of unfavourable social comparison, social defeat, and
      internal/external entrapment). RESULTS: Cross-sectional analysis showed that
      social defeat, but not other aspects of social rank, was independently predictive
      of a diagnosis of PTSD. Longitudinal analysis showed that greater social defeat
      at baseline predicted less improvement in PTSD symptoms, whereas greater
      reduction in social defeat over the 6-month follow-up predicted greater
      improvement in PTSD symptoms. CONCLUSIONS: In addition to the implications for
      understanding the role of social (rather than individual mental) defeat in the
      aetiology of PTSD, interventions could usefully incorporate methods that either
      increase social status or else minimize the impact of low status (e.g., through
      the use of compassion-focused approaches).

PMID- 24117911
TI  - 'Jumping to conclusions' in first-episode psychosis: a longitudinal study.
AB  - OBJECTIVES: People with psychotic symptoms are reported to have a characteristic
      reasoning style in which they jump to conclusions. To date, little research has
      been conducted to investigate if this style changes over time and is associated
      with improvements or worsening of symptoms. This study considered these
      questions. METHODS: Thirty-one service users were recruited from a first-episode
      service and completed measures of reasoning, psychotic, and non-psychotic
      symptomatology at two time points over 2 years. RESULTS: Over time, people with
      psychosis generally became less hasty in their decision-making. Those who became
      less hasty in their reasoning were less symptomatic. For those who remained very
      hasty in their reasoning, this was associated with a worsening specifically of
      the delusional beliefs. CONCLUSIONS: This work supports the notion that there is
      a critical time in the first few years of psychosis during which symptoms and
      reasoning can change. However, where reasoning style does not change, this may be
      associated with greater difficulties associated with delusional beliefs.

PMID- 24117912
TI  - Anxiety levels in clinically referred children and their parents: examining the
      unique influence of self-reported attachment styles and interview-based
      reflective functioning in mothers and fathers.
AB  - OBJECTIVE: Although much is known about childhood anxiety disorders, the
      differential contributions by mothers and fathers to child anxiety is poorly
      understood. This study examined the relation between child anxiety and parental
      level of psychopathology, attachment style, and reflective functioning (RF).
      DESIGN: Thirty-eight clinically anxious children aged 7-12 years (55.3% female)
      referred for treatment and their parents (37 mothers, 34 fathers) participated in
      the study. METHOD: Reflective functioning was coded based on Adult Attachment
      Interviews. Self-report questionnaires on attachment and psychopathology were
      administered. RESULTS: Paternal psychopathology, attachment avoidance, and
      attachment anxiety as well as maternal attachment anxiety were associated with
      child anxiety. Mothers had higher RF abilities than fathers. Lower levels of RF
      in mothers and higher levels of attachment avoidance in fathers explained 42% of
      the variance in anxiety levels of the child. CONCLUSION: Mothers and fathers may
      provide unique contributions to the development of child anxiety. The findings
      highlight the importance of considering fathers as well as mothers in research
      and treatment for childhood anxiety disorders.

PMID- 24117913
TI  - Attributional biases, paranoia, and depression in early psychosis.
AB  - OBJECTIVES: Attributional biases to externalize blame for negative events
      (externalizing bias) and to target other people for blame (personalizing bias)
      may constitute a vulnerability to psychosis. However, most research to date has
      only examined attributional biases in chronic patients. We examined attributional
      style, paranoia, and depression in early psychosis patients to assess the primacy
      of attributional biases in psychosis. DESIGN: A quasi-experimental design was
      adopted to compare the attributional style of patients and controls. Correlates
      of attributional style were also examined. METHODS: Early psychosis patients and
      age- and gender-matched healthy controls completed the 'Internal, Personal and
      Situational Attributions Questionnaire'. Paranoid tendencies, suspiciousness, and
      depression were also assessed in both groups, while severity of current symptoms
      was assessed in patients. RESULTS: A high proportion of patients had persecutory
      delusions. These patients, however, did not differ from controls in externalizing
      or personalizing bias. Whereas suspiciousness and persecutory delusions in
      patients associated with externalizing bias, no bias measures associated with
      paranoid tendencies in either patients or controls. Counter to the pattern seen
      for endogenous depression, depression in patients was associated with an
      increased tendency to attribute events to self and a decreased tendency to
      attribute events to circumstances. CONCLUSIONS: These preliminary findings raise
      doubts about the primacy of attributional biases in psychosis. The novel findings
      with regard to depression warrant further investigation and suggest that young
      people, who develop depression after the onset of psychosis, may experience a
      need to re-establish a sense of personal control over life events that appear
      unpredictable.

PMID- 24117914
TI  - Attachment: developmental pathways to affective dysregulation in young people at
      ultra-high risk of developing psychosis.
AB  - OBJECTIVE: Embedded in attachment theory is its association with affect
      regulation, which provides a framework for affective dysregulation in the
      emerging psychosis. METHOD: Fifty-one participants meeting criteria for ultra
      high risk (UHR) of developing psychosis were recruited from a youth mental health
      service within the United Kingdom. At intake baseline, prior to starting
      therapeutic intervention, all clients were assessed on measures of affective
      dysregulation and attachment. RESULTS: A large proportion of our sample (N = 51)
      reported clinically significant levels of depression (78%), state anxiety (59%),
      and social anxiety (65%). Eighty per cent of the UHR sample was insecurely
      attached. Insecure attachment was significantly associated with elevated
      depression and social anxiety. Attachment styles were associated with anxiety,
      depression, and social anxiety. There was no support for a mediating role of
      social anxiety between attachment styles and depression. CONCLUSION: Clinically
      significant levels of distress and anxiety experienced by the young people at
      high risk of psychosis. Clinical implications for the treatment of affective
      dysregulation in young people at UHR in relation to their attachment styles have
      been discussed.

PMID- 24117916
TI  - The influence of individual, group, and relative self-esteem on outcome for
      patients undergoing group cognitive-behavioural therapy treatment.
AB  - OBJECTIVES: Despite a strong association between individual self-esteem and
      treatment outcome in group cognitive-behavioural therapy (GCBT), no study has
      investigated how patient outcomes might be influenced by an individual's self
      esteem relative to other group members. DESIGN: The study comprised a
      retrospective examination of patients' data and used a multiple regression
      analysis to identify predictors of treatment outcome. Patients' pre-treatment
      self-esteem scores were assessed on a continuum and assigned to be low, medium,
      or high. Therapy groups were assigned to be either low, balanced or high self
      esteem groups based on averaged self-esteem scores of participants. METHODS: In
      this study, 3,878 patients who had completed a 10-day intensive cognitive
      behavioural group therapy programme at a private psychiatric facility were
      included in the study. The Rosenberg Self-Esteem measure was chosen to assess
      self-esteem. The three subscales of the Depression Anxiety Stress Scales were
      used as the outcome measures. RESULTS: Patient outcomes were influenced by pre
      treatment self-esteem scores, such that higher initial self-esteem was associated
      with better treatment outcomes. Low group self-esteem was predictive of
      significantly better outcomes for depression, relative to higher self-esteem
      groups. Additionally, the combined influence of high individual self-esteem and
      low group self-esteem was associated with significantly enhanced depression
      improvement. CONCLUSIONS: High self-esteem patients perform better on outcome
      measures following completion of GCBT. Low self-esteem groups show greater
      improvement in depression symptoms. Similar results for depression are achieved
      when patients with high self-esteem complete treatment in low self-esteem groups.

PMID- 24117915
TI  - Factorial invariance of the Patient Health Questionnaire and Generalized Anxiety
      Disorder Questionnaire.
AB  - OBJECTIVES: The UK's Improving Access to Psychological Therapies (IAPT) programme
      uses the Patient Health Questionnaire Depression Scale (PHQ-9; Kroenke, Spitzer,
      & Williams, , J. Gen. Intern. Med., 16, 606) and Generalized Anxiety Disorder
      Scale (GAD-7; Spitzer et al., Arch. Intern. Med., 166, 1092) to assess patients'
      symptoms of depression and anxiety respectively. Data are typically collected via
      telephone or face-to-face; however, no study has statistically investigated
      whether the questionnaires' items operate equivalently across these modes of data
      collection. This study aimed to address this omission. METHODS & RESULTS:
      Questionnaire data from patients registered with an IAPT service in London (N =
      23,672) were examined. Confirmatory factor analyses suggested that unidimensional
      factor structures adequately matched observed face-to-face and telephone data for
      the PHQ-9 and GAD-7. Invariance analyses revealed that while the PHQ-9 had
      equivalent factor loadings and latent means across data collection methods, the
      GAD-7 had equivalent factor loadings but unequal latent means. In support of the
      scales' convergent validity, positive associations between scores on the PHQ-9
      and GAD-7 emerged. CONCLUSIONS: With the exception of the GAD-7's latent means,
      the questionnaires' factor loadings and latent means were equivalent. This
      suggests that clinicians may meaningfully compare PHQ-9 data collected face-to
      face and by telephone; however, such comparisons with the GAD-7 should be done
      with caution.

PMID- 24117917
TI  - Mandibular corrective osteotomy using novel locking compression plate 3.5/4.5/5.0
      mm metaphyseal plates.
AB  - OBJECTIVE: To describe a technique and the outcome of using 3.5/4.5/5.0
      Metaphyseal Locking Compression Plate for corrective osteotomy of mandibular
      brachygnathia. STUDY DESIGN: Clinical report. ANIMAL: Eight-month Thoroughbred
      horse. METHODS: Severe mandibular brachygnathia was surgically treated by
      corrective osteotomy and fixation with 2 LCP 3.5/4.5/5.0 Metaphyseal plates
      inserted using minimally invasive technique. RESULTS: Severe mandibular
      brachygnathia was treated successfully with minor complications and stable
      fixation after 3 months. Cosmetic outcome and owner satisfaction was excellent.
      CONCLUSIONS: Corrective osteotomy and fixation with LCP 3.5/4.5/5.0 Metaphyseal
      plates can be considered as a surgical technique for correction of severe
      mandibular brachygnathia in weanlings.

PMID- 24117918
TI  - Compliance with the current 12-month deferral for male-to-male sex in Australia.
AB  - BACKGROUND AND OBJECTIVES: In Australia since 2000, donors are deferred for 12
      months since last male-to-male sexual contact. There is no estimate of the
      prevalence of non-compliance (i.e. failure to disclose a risk during the
      predonation interview which would lead to deferral) with the policy in Australia;
      however, published studies elsewhere indicate a range of 0.8-2.3% [corrected]. We
      investigated the rate of, timing and motivation for non-compliance. MATERIALS AND
      METHODS: A nationally representative sample of donors who had made a recent
      donation negative for transfusion-transmissible infection testing was surveyed
      using an anonymous, online instrument. Non-compliance was considered as a 'yes'
      response to the current screening question. Non-compliers were requested to
      define the timing of the last sexual contact relevant to their most recent
      donation. Univariate and multivariate regression analyses were used to define
      factors associated with non-compliance. RESULTS: Of 14 476 responses from male
      donors, 34 (0.23%, 95% CI: 0.16-0.33%) were non-compliant of whom 24 (0.17%, 95%
      CI: 0.11-0.25%) had contact within 6 months of donation. Factors significantly
      associated with non-compliance included: multiple sexual partners, history of
      injecting drug use, perception of a lack of privacy during interview and
      preference for a computer-based questionnaire. CONCLUSION: Our study confirms
      high compliance (>99.7%) to the 12-month deferral for male-to-male sex in
      Australia providing reassuring evidence for the efficacy of the screening
      question. Issues of 'privacy' and 'discomfort' associated with disclosure suggest
      the use of validated audio computer-assisted structured interview as a possible
      option for improving compliance with the donor questionnaire.

PMID- 24117919
TI  - Explaining intraspecific diversity in plant secondary metabolites in an
      ecological context.
AB  - Plant secondary metabolites (PSMs) are ubiquitous in plants and play many
      ecological roles. Each compound can vary in presence and/or quantity, and the
      composition of the mixture of chemicals can vary, such that chemodiversity can be
      partitioned within and among individuals. Plant ontogeny and environmental and
      genetic variation are recognized as sources of chemical variation, but recent
      advances in understanding the molecular basis of variation may allow the future
      deployment of isogenic mutants to test the specific adaptive function of
      variation in PSMs. An important consequence of high intraspecific variation is
      the capacity to evolve rapidly. It is becoming increasingly clear that trait
      variance linked to both macro- and micro-environmental variation can also evolve
      and may respond more strongly to selection than mean trait values. This research,
      which is in its infancy in plants, highlights what could be a missing piece of
      the picture of PSM evolution. PSM polymorphisms are probably maintained by
      multiple selective forces acting across many spatial and temporal scales, but
      convincing examples that recognize the diversity of plant population structures
      are rare. We describe how diversity can be inherently beneficial for plants and
      suggest fruitful avenues for future research to untangle the causes and
      consequences of intraspecific variation.

PMID- 24117920
TI  - Asymptomatic carotid disease--a new tool for assessing neurological risk.
AB  - Active carotid plaques are associated with atheroembolism and neurological
      events; its identification is crucial for stroke prevention. High-definition
      ultrasound (HDU) can be used to recognize plaque structure in carotid bifurcation
      stenosis associated with plaque vulnerability and occurrence of brain ischemic
      events. A new computer-assisted HDU method to study the echomorphology of the
      carotid plaque and to determine a risk score for developing appropriate symptoms
      is proposed in this study. Plaque echomorphology characteristics such as presence
      of ulceration at the plaque surface, juxta-luminal location of echolucent areas,
      echoheterogeneity were obtained from B-mode ultrasound scans using several image
      processing algorithms and were combined with measurement of severity of stenosis
      to obtain a clinical score--enhanced activity index (EAI)--which was correlated
      with the presence or absence of ipsilateral appropriate ischemic symptoms. An
      optimal cutoff value of EAI was determined to obtain the best separation between
      symptomatic (active) from asymptomatic (inactive) plaques and its diagnostic
      yield was compared to other 2 reference methods by means of receiver-operating
      characteristic (ROC) analysis. Classification performance was evaluated by leave
      one-patient-out cross-validation applied to a cohort of 146 carotid plaques from
      99 patients. The proposed method was benchmarked against (a) degree of stenosis
      criteria and (b) earlier proposed activity index (AI) and demonstrated that EAI
      yielded the highest accuracy up to an accuracy of 77% to predict asymptomatic
      plaques that developed symptoms in a prospective cross-sectional study. Enhanced
      activity index is a noninvasive, easy to obtain parameter, which provided
      accurate estimation of neurological risk of carotid plaques.

PMID- 24117921
TI  - A comparative pharmacokinetic estimate of mercury in U.S. Infants following
      yearly exposures to inactivated influenza vaccines containing thimerosal.
AB  - The use of thimerosal preservative in childhood vaccines has been largely
      eliminated over the past decade in the United States because vaccines have been
      reformulated in single-dose vials that do not require preservative. An exception
      is the inactivated influenza vaccines, which are formulated in both multidose
      vials requiring preservative and preservative-free single-dose vials. As part of
      an ongoing evaluation by USFDA of the safety of biologics throughout their
      lifecycle, the infant body burden of mercury following scheduled exposures to
      thimerosal preservative in inactivated influenza vaccines in the United States
      was estimated and compared to the infant body burden of mercury following daily
      exposures to dietary methylmercury at the reference dose established by the
      USEPA. Body burdens were estimated using kinetic parameters derived from
      experiments conducted in infant monkeys that were exposed episodically to
      thimerosal or MeHg at identical doses. We found that the body burden of mercury
      (AUC) in infants (including low birth weight) over the first 4.5 years of life
      following yearly exposures to thimerosal was two orders of magnitude lower than
      that estimated for exposures to the lowest regulatory threshold for MeHg over the
      same time period. In addition, peak body burdens of mercury following episodic
      exposures to thimerosal in this worst-case analysis did not exceed the
      corresponding safe body burden of mercury from methylmercury at any time, even
      for low-birth-weight infants. Our pharmacokinetic analysis supports the
      acknowledged safety of thimerosal when used as a preservative at current levels
      in certain multidose infant vaccines in the United States. 

PMID- 24117922
TI  - Autocatalytic growth of biofunctionalized antibacterial silver nanoparticles.
AB  - Development of eco-friendly processes for nanosynthesis is gaining importance
      owing to the widespread application of nanoparticles (NPs). In the present study,
      we have explained the mechanism and kinetics of bioreduction in the biosynthesis
      of silver nanoparticles (AgNPs) using aqueous leaf extract of Rhizophora
      apiculata. Spectrophotometric methods were employed to quantify the bioactive
      molecules present before and after the reduction process. The results showed that
      the polyphenols were the main components responsible for the biosynthesis of
      AgNPs, which was further confirmed by Fourier transform infrared spectroscopy.
      The kinetics of formation of AgNPs were monitored by time-resolved
      spectrophotometric and X-ray diffraction studies, which revealed that the NP
      formation is an autocatalytic process with a rate constant of 1.9 * 10(-2)  Min(
      1) . The NPs were characterized using spectroscopic and microscopic techniques
      like ultraviolet-visible absorption spectroscopy, dynamic light scattering,
      transmission electron microscopy, scanning electron microscopy-energy-dispersive
      X-ray spectroscopy, and X-ray diffraction. The biogenic AgNPs showed substantial
      inhibitory activity to Proteus mirabilis, Pseudomonas aeruginosa, Escherichia
      coli, and Staphylococcus aureus with minimum inhibitory concentration values of
      2.5, 12.5, 2.5, and 31.25 MUg/mL, respectively. The current research provides an
      insight into the mechanistic aspects of bioreduction and formation of AgNPs. 

PMID- 24117923
TI  - A gut microbiota-targeted dietary intervention for amelioration of chronic
      inflammation underlying metabolic syndrome.
AB  - Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota
      contributes to the development of obesity-related metabolic disorders.
      Modification of gut microbiota by a diet to balance its composition becomes a
      promising strategy to help manage obesity. A dietary scheme based on whole
      grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was
      designed to meet human nutritional needs as well as balance the gut microbiota.
      Ninety-three of 123 central obese volunteers (BMI >= 28 kg m(-2) ) completed a
      self-controlled clinical trial consisting of 9-week intervention on WTP diet
      followed by a 14-week maintenance period. The average weight loss reached 5.79 +/
      4.64 kg (6.62 +/- 4.94%), in addition to improvement in insulin sensitivity,
      lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that
      phylotypes related to endotoxin-producing opportunistic pathogens of
      Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while
      those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased.
      Gut permeability, measured as lactulose/mannitol ratio, was decreased compared
      with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein
      was also significantly reduced, with concomitant decrease in tumor necrosis
      factor-alpha, interleukin-6, and an increase in adiponectin. These results
      suggest that modulation of the gut microbiota via dietary intervention may
      enhance the intestinal barrier integrity, reduce circulating antigen load, and
      ultimately ameliorate the inflammation and metabolic phenotypes. 

PMID- 24117924
TI  - Water stress and recovery in the performance of two Eucalyptus globulus clones:
      physiological and biochemical profiles.
AB  - Eucalyptus plantations are among the most productive forest stands in Portugal
      and Spain, being mostly used for pulp production and, more recently, as an energy
      crop. However, the region's Mediterranean climate, with characteristic severe
      summer drought, negatively affects eucalypt growth and increases mortality.
      Although the physiological response to water shortage is well characterized for
      this species, evidence about the plants' recovery ability remains scarce. In
      order to assess the physiological and biochemical response of Eucalyptus globulus
      during the recovery phase, two genotypes (AL-18 and AL-10) were submitted to a 3
      week water stress period at two different intensities (18 and 25% of field
      capacity), followed by 1 week of rewatering. Recovery was assessed 1 day and 1
      week after rehydration. Drought reduced height, biomass, water potential, NPQ and
      gas exchange in both genotypes. Contrarily, the levels of pigments, chlorophyll
      fluorescence parameters (F(v) /F(m) and (phiPSII)), MDA and ABA increased. During
      recovery, the physiological and biochemical profile of stressed plants showed a
      similar trend: they experienced reversion of altered traits (MDA, ABA, E, g(s),
      pigments), while other parameters did not recover ((phiPSII), NPQ). Furthermore,
      an overcompensation of CO(2) assimilation was achieved 1 week after rehydration,
      which was accompanied by greater growth and re-establishment of oxidative
      balance. Both genotypes were tolerant to the tested conditions, although clonal
      differences were found. AL-10 was more productive and showed a more rapid and
      dynamic response to rehydration (namely in carotenoid content, (phiPSII) and NPQ)
      compared to clone AL-18.

PMID- 24117925
TI  - Postharvest transfer and survival of Salmonella enterica serotype enteritidis on
      living lettuce.
AB  - The potential for postharvest transfer of Salmonella to 'living lettuce' is not
      well understood. In this study, the transfer of Salmonella enterica Enteritidis
      (6 log CFU g(-1) ) from worker hands or contaminated roots to leaves of living
      lettuce was quantified. Transfer rates of Salmonella from contaminated gloves to
      sequentially handled lettuce heads ranged from 94% to head 1, 82% to head 2 and
      69% to head 3. On average, 2.9 +/- 0.1 log CFU g(-1) (64%) Salmonella was
      transferred from inoculated roots to leaves resulting from typical postharvest
      handling activities for living lettuce. Salmonella persisted on leaves stored at
      recommended storage temperatures (4 degrees C) and increased 0.5 log CFU g(-1)
      when stored at temperature abuse conditions (12 degrees C). Salmonella increased
      1.6 log CFU g(-1) on roots after 18-day storage at 12 degrees C, emphasizing the
      need to maintain temperature control to reduce the risk of human illness.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Hydroponically grown lettuce packaged in
      plastic clamshells with intact roots, marketed as 'living lettuce', is increasing
      in popularity due to its extended shelf life. This study demonstrates the
      transfer of Salmonella from contaminated worker hands and contaminated roots to
      leaves where it persisted at 4 degrees C for 18 day. Temperature abuse (12
      degrees C) increased Salmonella on roots and leaves. These findings suggest that
      failure to maintain temperatures below 12 degrees C can pose a risk for consumers
      purchasing living lettuce at markets where recommended storage temperatures are
      not maintained.

PMID- 24117926
TI  - Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic
      keratosis and their implications.
AB  - BACKGROUND: Basal cell carcinoma (BCC) has a characteristic stroma, but less is
      known about the dermal characteristics associated with melanoma in situ (MIS) and
      actinic keratosis (AK). MATERIALS AND METHODS: Dermal changes were studied in 301
      specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from
      90 randomly selected cases of those entities were used to assess the predictive
      value of the dermal changes. Agreement with the final diagnosis was calculated
      using kappa coefficient (kappa). RESULTS: Fibromyxoid stroma was present in 82%
      of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK
      specimens (p < 0.05). A lichenoid inflammatory infiltrate was frequently
      associated with AK and a perifollicular infiltrate with periadnexal fibrosis with
      MIS. Blinded evaluation of images of the dermal changes associated with the
      tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by
      the three appraisers. Coefficient of agreement in blinded imaged evaluation with
      the actual diagnosis was higher in the BCC and MIS compared with AK (kappa =
      0.37, p = 0.0001; kappa = 0.2, p = 0.0005 and kappa = -0.06, p = 0.84,
      respectively). CONCLUSION: Dermal features may be helpful in predicting the
      correct diagnosis when tumor is not visible.

PMID- 24117927
TI  - Different surgical techniques and L-carnitine supplementation in an experimental
      varicocele model.
AB  - We aimed to investigate the impact of various varicocelectomy techniques and/or L
      carnitine as an adjunct treatment, following the emergence of oxidative stress,
      on the expression levels of SCF/c-kit signalling pathways in spermatogenesis.
      Forty-two rats were divided into seven groups: group 1 (G1) control; group 2 (G2)
      sham; group 3 (G3) varicocele; group 4 (G4) varicocele + varicocelectomy with
      testicular nonartery sparing; group 5 (G5) same as G4 but with artery sparing;
      group 6 (G6) same as G4 but with L-carnitine and group 7 (G7) same as G5 with L
      carnitine. mRNA expression levels of SCF and c-kit were measured quantitatively
      using real-time polymerase chain reaction. CASP-3 activity at protein level was
      determined, and histological evaluation was performed. mRNA expression level of
      SCF increased in G6 as compared to control group (3.52-folds change; P = 0.035),
      whereas mRNA expression level of c-kit gene remained the same. We found that in
      the left testis of G6 group, mRNA expression level of SCF increased 2.2-folds in
      comparison with the right testis (P < 0.05). There were no statistically
      significant differences in the CASP-3 protein expression levels between the
      control and other groups. When Cosentino Score analyses of immunostaining were
      conducted, we observed no significant differences among groups. Spermatogenic
      failure could be primarily due to a sertoli cell dysfunction. Although surgical
      treatment has been the best option for management of varicocele, auxiliary agents
      like L-carnitine may be considered as supportive treatment regimes in addition to
      conventional surgical treatments.

PMID- 24117928
TI  - Validation of obstetric estimate using early ultrasound: 2007 California birth
      certificates.
AB  - BACKGROUND: Obstetric estimate (OE) of gestational age, recently added to the
      standard US birth certificate, has not been validated. Using early ultrasound
      based gestational age (prior to 20 weeks gestation) as the criterion standard, we
      estimated the prevalence of preterm delivery and the sensitivity and positive
      predictive value (PPV) of gestational age estimates based on OE. METHODS: We
      analyzed 165 148 singleton livebirth records (38% of California livebirths during
      the study period) with linked early ultrasound information from a statewide
      California prenatal screening programme. OE of gestational age estimates was
      obtained from birth certificates. RESULTS: Prevalence of preterm delivery (<37
      weeks gestation) was higher based on early ultrasound (8.1%) compared with
      preterm delivery based on OE (7.1%). Sensitivity for preterm birth when using OE
      for gestational age was 74.9% (95% confidence interval [CI] [74.1, 75.6]), and
      PPV was 85.1% (95% CI [84.4, 85.7]). Incongruence, defined as a >= 14-day
      difference between early-ultrasound-derived gestational age and OE, was 3.4%.
      CONCLUSIONS: OE reported on the birth certificate may underestimate the
      prevalence of preterm delivery, particularly among women of non-Hispanic non
      white race and ethnicity and women with lower educational attainment, public
      insurance at time of delivery, and missing prepregnancy BMI. Additional
      validation studies in other samples of births are needed.

PMID- 24117929
TI  - Can upwelling signals be detected in intertidal fishes of different trophic
      levels?
AB  - For intertidal fishes belonging to three species, the herbivore Scartichthys
      viridis (Blenniidae), the omnivore Girella laevifrons (Kyphosidae) and the
      carnivore Graus nigra (Kyphosidae), mass and body size relationships were higher
      in individuals from an upwelling zone compared with those from a non-upwelling
      zone. RNA:DNA were higher in the herbivores and omnivores from the upwelling
      zone. Higher biomass and RNA:DNA in the upwelling intertidal fishes may be a
      consequence of an increased exposure to higher nutrient availability, suggesting
      that increased physiological conditioning in vertebrates from upwelling areas can
      be detected and measured using intertidal fishes of different trophic levels. 

PMID- 24117930
TI  - Neurological symptoms in hospitalised patients: do we assess hyponatraemia with
      sufficient care?
AB  - AIM: To review the incidence of hyponatraemic encephalopathy in children treated
      in a tertiary care centre hospital, together with the clinical setting and
      clinical management of these cases. METHODS: Retrospective descriptive study by
      chart review of patients admitted to hospital during 2000-2010. Patients older
      than 1 month were included who had severe hyponatraemia (sodium concentration
      <125 mmol/L) on admission or during their hospital stay and co-incidental
      neurological symptoms. Epidemiological, clinical, laboratory and therapeutic data
      were collected. RESULTS: We analysed 41 cases of severe hypotonic hyponatraemia
      and neurological symptoms compatible with hyponatraemic encephalopathy. Boys
      accounted for 56.1% patients, and the median age was 1 year. Hyponatraemia was
      acquired in hospital by 61% of the patients, and 88% of those patients were
      receiving intravenous hypotonic fluids. The most frequent neurological symptom
      was seizures. The most common therapeutic strategy was sodium supplementation and
      antiepileptic drugs. Hypertonic fluids were only used in the initial treatment of
      16 patients. There were two deaths related to hyponatraemic encephalopathy.
      CONCLUSION: Hyponatraemia should always be considered a cause of neurological
      symptoms in hospitalised patients. Treatment should be prompt to prevent
      neurological sequelae and death. Current recommendations for fluid management in
      hospitalised children should be reviewed.

PMID- 24117931
TI  - Stress and pain: their relationship to health related quality of life (HRQL) for
      horses.

PMID- 24117932
TI  - Birth transitions: pathophysiology, the onset of consciousness and possible
      implications for neonatal maladjustment syndrome in the foal.

PMID- 24117933
TI  - The use of a tongue tie alters laryngohyoid position in the standing horse.
AB  - REASONS FOR PERFORMING STUDY: The use of tongue ties in racing is common, yet
      there are few data to support their efficacy. In order to make appropriate
      recommendations for clinical practice and policy on tongue ties, data documenting
      their effect on upper airway structure are necessary. OBJECTIVES: To determine
      the effect of a tongue tie on the resting laryngohyoid position of the standing
      horse. STUDY DESIGN: Experimental study. METHODS: Twelve normal Standardbred
      horses were subjected to ultrasonographic measures of laryngohyoid position
      during 3 phases of tack application: Phase I--halter and lead; Phase II--bit,
      bridle, harness and check applied; and Phase III--as in Phase II but with the
      tongue tie added. RESULTS: Compared to Phase I, during Phase III with the
      application of a tongue tie a significant difference between lingual process
      position was noted both rostrally and caudally (P<0.001 and P<0.001), such that
      the tongue tie resulted in an increase in lingual process depth. The tongue tie
      in Phase III resulted in a decrease in depth of the thyroid cartilage and
      basihyoid bone compared to the Phase I location (P = 0.007 and P = 0.0047).
      CONCLUSION: The use of a tongue tie has a significant effect on the basihyoid and
      thyroid cartilage positions in the standing horse. POTENTIAL RELEVANCE: This is
      the first report documenting a difference in laryngohyoid morphology following
      the application of a tongue tie, providing evidence that the use of a tongue tie
      has a measurable effect on upper airway structure. The functional implications of
      this finding are yet to be elucidated.

PMID- 24117934
TI  - Influenza: are we protecting our horses effectively?

PMID- 24117935
TI  - Equine influenza: antigenic drift and implications for vaccines.

PMID- 24117936
TI  - Vaccination for equine influenza: the sports regulator's viewpoint.

PMID- 24117937
TI  - Influenza vaccine strains: licensing perspectives.

PMID- 24117938
TI  - Equine influenza vaccines in Europe: a view from the animal health industry.

PMID- 24117939
TI  - Instant-quality fluorescence in-situ hybridization as a new tool for HER2 testing
      in breast cancer: a comparative study.
AB  - AIMS: HER2 instant-quality fluorescence in-situ hybridization (IQFISH) is a new
      fluorescence in-situ hybridization (FISH) assay developed with a non-toxic buffer
      that reduces the hybridization time to 1-2 h, enabling a turnaround time of 3 h
      30 min from dewax to counting. The aim of this study was to compare assessment of
      HER2 status using IQFISH and assessment using standard FISH. METHODS AND RESULTS:
      We selected 160 breast cancer samples according to their HER2 status as
      determined by immunohistochemistry (IHC) in a retrospective multicentre cohort
      (40 cases in each scoring category, i.e. 0/1+/2+/3+). Each participating site (n
      = 5) constructed its tissue microarray (TMA) of 32 archival cases and sent it to
      the central site (site 1). HER2 IHC, HER2 FISH and HER2 IQFISH were performed
      blindly at site 1. IQFISH provided excellent quality signals without any
      background staining, thus allowing excellent reading conditions even on TMA.
      Statistical analysis showed almost perfect agreement between IQFISH and FISH
      (99.3%, kappa = 0.98). The only discordant case was an equivocal one with an
      HER2/CEP17 ratio near the ASCO/CAP cut-off. CONCLUSIONS: The highly concordant
      data support IQFISH as a useful alternative to FISH, allowing reliable assessment
      of HER2 status. Use of this method could lead to reporting of HER status to the
      oncologist within a day.

PMID- 24117940
TI  - The roles of emotion regulation and ruminative thoughts in non-suicidal self
      injury.
AB  - OBJECTIVES: This study explored how cognitive reappraisal, expressive
      suppression, and facets of ruminative thinking could be brought together in a
      model to explain non-suicidal self-injury (NSSI) in the context of experiencing
      stressful life events and psychological distress. METHODS: Data from 2,507
      participants aged 12-18 years (68% female, mean age 13.93 years) recruited from
      40 Australian secondary schools were analysed, including 254 participants with a
      history of NSSI (72% female, mean age 14.21 years). Participants completed a self
      report questionnaire assessing the constructs of interest. RESULTS: Although
      meeting minimum fit indices, our hypothesized model showed poorer fit compared to
      an empirically derived model. There was little evidence for the mediating role of
      psychological distress in NSSI, and we found adverse life events, psychological
      distress, emotion regulation, and two facets of ruminative thinking
      (counterfactual thinking and anticipatory thoughts) had direct, though weak,
      relationships with NSSI. Among the subsample of adolescents with a history of
      NSSI, anticipatory rumination moderated the relationship between psychological
      distress and NSSI, while cognitive reappraisal demonstrated a direct, although
      weak relationship with NSSI. CONCLUSIONS: Our observations suggest that, among
      adolescents, contextual, social, and behavioural factors may have a strong
      influence on NSSI and this may suggest that prevention and treatment efforts for
      NSSI among adolescents need to focus on contextual, social, and behavioural
      factors.

PMID- 24117941
TI  - Premature and ectopic anthocyanin formation by silencing of anthocyanidin
      reductase in strawberry (Fragaria * ananassa).
AB  - Strawberry (Fragaria * ananassa) is a fruit crop with a distinct biphasic
      flavonoid biosynthesis. Whereas, in the immature receptacle, high levels of
      proanthocyanidins accumulate, which are associated with herbivore deterrence and
      pathogen defense, the prominent color-giving anthocyanins are primarily produced
      in ripe 'fruits' helping to attract herbivores for seed dispersal. Here,
      constitutive experimental down-regulation of one branch of proanthocyanidin
      biosynthesis was performed. As a result, the proportion of epicatechin monomeric
      units within the proanthocyanidin polymer chains was reduced, but this was not
      the case for the epicatechin starter unit. Shortened chain lengths of
      proanthocyanidins were also observed. All enzymatic activities for the production
      of color-giving anthocyanins were already present in unripe fruits at levels
      allowing a striking red anthocyanin phenotype in unripe fruits of the RNAi
      silencing lines. An immediately recognizable phenotype was also observed for the
      stigmata of flowers, which is another epicatechin-forming tissue. Thus, the down
      regulation of anthocyanidin reductase (ANR) induced a redirection of the
      proanthocyanidin pathway, leading to premature and ectopic anthocyanin
      biosynthesis via enzymatic glycosylation as the alternative pathway. This
      redirection is also seen in flavonol biosynthesis, which is paralleled by higher
      pollen viability in silencing lines. ANRi transgenic lines of strawberry provide
      a versatile tool for the study of the biological functions of proanthocyanidins.

PMID- 24117942
TI  - Autosomal-dominant Alzheimer's disease mutations at the same codon of amyloid
      precursor protein differentially alter Abeta production.
AB  - Autosomal-dominant Alzheimer's disease (ADAD) is a genetic disorder caused by
      mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studying
      the mechanisms underlying these mutations can provide insight into the pathways
      that lead to AD pathology. The majority of biochemical studies on APP mutations
      to-date have focused on comparing mechanisms between mutations at different
      codons. It has been assumed that amino acid position is a major determinant of
      protein dysfunction and clinical phenotype. However, the differential effect of
      mutations at the same codon has not been sufficiently addressed. In the present
      study we compared the effects of the aggressive ADAD-associated APP I716F
      mutation with I716V and I716T on APP processing in human neuroglioma and CHO-K1
      cells. All APP I716 mutations increased the ratio of Abeta42/40 and changed the
      product line preference of gamma-secretase towards Abeta38 production. In
      addition, the APP I716F mutation impaired the epsilon-cleavage and the fourth
      cleavage of gamma-secretase and led to abnormal APP beta-CTF accumulation at the
      plasma membrane. Taken together, these data indicate that APP mutations at the
      same codon can induce diverse abnormalities in APP processing, some resembling
      PSEN1 mutations. These differential effects could explain the clinical
      differences observed among ADAD patients bearing different APP mutations at the
      same position. The amyloid precursor protein (APP) I716F mutation is associated
      with autosomal dominant Alzheimer's disease with the youngest age-at-onset for
      the APP locus. Here, we describe that this mutation, when compared to two other
      familial Alzheimer's disease mutations at the same codon (I716V and I716T),
      interfered distinctly with gamma-secretase cleavage. While all three mutations
      direct gamma-secretase cleavage towards the 48->38 production line, the APP I716F
      mutation also impaired the epsilon-cleavage and the fourth cleavage of gamma
      secretase, resembling a PSEN1 mutation. These features may contribute to the
      aggressiveness of this mutation.

PMID- 24117943
TI  - Reciprocal relationship of Tn/NF-kappaB and sTn as an indicator of the prognosis
      of oral squamous cell carcinoma.
AB  - AIMS: In order to determine whether the expression of tumour-associated
      carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear
      factor-kappaB (NF-kappaB), is associated with the invasiveness of oral squamous
      cell carcinoma (OSCC), this study has attempted to investigate the correlation of
      the aforementioned markers with the well-established invasive pattern grading
      score (IPGS) and clinicopathological parameters. METHODS AND RESULTS: Specimens
      from 143 OSCC patients with classified clinicopathological parameters and IPGS
      were stained immunohistochemically using anti-Tn, sTn and NF-kappaB antibodies.
      Our results showed that the expression of both Tn and NF-kappaB was correlated
      positively with staging (P = 0.036; P = 0.015), recurrence (P < 0.001; P < 0.001)
      and distant metastasis (P = 0.005; P = 0.009), as well as with IPGS, while the
      expression of sTn was correlated inversely. In addition, poor survival was
      associated with overexpression of Tn and NF-kappaB but not with expression of
      sTn. CONCLUSIONS: Our results indicate that a reciprocal relationship between Tn
      and sTn expression may serve as a reliable indicator for OSCC prognostic
      evaluation. In addition, expression of Tn rather than sTn may play an important
      role in deeply invasive OSCC via regulation of NF-kappaB signalling.

PMID- 24117944
TI  - The beneficial effects of melatonin against heart mitochondrial impairment during
      sepsis: inhibition of iNOS and preservation of nNOS.
AB  - While it is accepted that the high production of nitric oxide (NO) by the
      inducible nitric oxide synthase (iNOS) impairs cardiac mitochondrial function
      during sepsis, the role of neuronal nitric oxide synthase (nNOS) may be
      protective. During sepsis, there is a significantly increase in the expression
      and activity of mitochondrial iNOS (i-mtNOS), which parallels the changes in
      cytosolic iNOS. The existence of a constitutive NOS form (c-mtNOS) in heart
      mitochondria has been also described, but its role in the heart failure during
      sepsis remains unclear. Herein, we analyzed the changes in mitochondrial
      oxidative stress and bioenergetics in wild-type and nNOS-deficient mice during
      sepsis, and the role of melatonin, a known antioxidant, in these changes. Sepsis
      was induced by cecal ligation and puncture, and heart mitochondria were analyzed
      for NOS expression and activity, nitrites, lipid peroxidation, glutathione and
      glutathione redox enzymes, oxidized proteins, and respiratory chain activity in
      vehicle- and melatonin-treated mice. Our data show that sepsis produced a similar
      induction of iNOS/i-mtNOS and comparable inhibition of the respiratory chain
      activity in wild-type and in nNOS-deficient mice. Sepsis also increased
      mitochondrial oxidative/nitrosative stress to a similar extent in both mice
      strains. Melatonin administration inhibited iNOS/i-mtNOS induction, restored
      mitochondrial homeostasis in septic mice, and preserved the activity of nNOS/c
      mtNOS. The effects of melatonin were unrelated to the presence or the absence of
      nNOS. Our observations show a lack of effect of nNOS on heart bioenergetic
      impairment during sepsis and further support the beneficial actions of melatonin
      in sepsis. 

PMID- 24117945
TI  - Exercise performance of chronic heart failure patients in the early period of
      support by an axial-flow left ventricular assist device as destination therapy.
AB  - Axial-flow left ventricular assist devices (LVADs) are increasingly used as
      destination therapy in end-stage chronic heart failure (CHF), as they improve
      survival and quality of life. Their effect on exercise tolerance in the early
      phase after implantation is still unclear. The aim of this study was to evaluate
      the effect of LVADs on the exercise capacity of a group of CHF patients within 2
      months after initiation of circulatory support. Cardiopulmonary exercise test
      data were collected for 26 consecutive LVAD-implanted CHF patients within 2
      months of initiation of assistance; the reference group consisted of 30 CHF
      patients not supported by LVAD who were evaluated after an episode of acute heart
      failure. Both LVAD and reference groups showed poor physical performance; LVAD
      patients achieved lower workload (LVAD: 36.3 +/- 9.0 W, reference: 56.6 +/- 18.2
      W, P < 0.001) but reached a similar peak oxygen uptake (peak VO2 ; LVAD: 12.5 +/-
      3.0 mL/kg/min, reference: 13.6 +/- 2.9 mL/kg/min, P = ns) and similar percentages
      of predicted peak VO2 (LVAD: 48.8 +/- 13.9%, reference: 54.2 +/- 15.3%, P = ns).
      While the values of the O2 uptake efficiency slope were 12% poorer in LVAD
      patients than in reference patients (1124.2 +/- 226.3 vs. 1280.2 +/- 391.1; P =
      ns), the kinetics of VO2 recovery after exercise were slightly better in LVAD
      patients (LVAD: 212.5 +/- 62.5, reference: 261.1 +/- 80.2 sec, P < 0.05). In the
      first 2 months after initiation of circulatory support, axial-flow LVAD patients
      are able to sustain a low-intensity workload; though some cardiopulmonary
      exercise test parameters suggest persistence of a marked physical deconditioning,
      their cardiorespiratory performance is similar to that of less compromised CHF
      patients, possibly due to positive hemodynamic effects beginning to be produced
      by the assist device. 

PMID- 24117946
TI  - Endoscopic resection for duodenal carcinoid tumors: a multicenter, retrospective
      study.
AB  - BACKGROUND AND AIM: Gastrointestinal carcinoid tumors < 10 mm in diameter and
      limited to the submucosal layer demonstrate a low frequency of lymph node and
      distant metastasis, and are suitable for endoscopic treatment. The aim of this
      study was to assess the efficacy, safety, and long-term prognosis of endoscopic
      resections for the treatment of duodenal carcinoid tumors. METHODS: This study
      included a total of 41 duodenal carcinoid tumors in 38 patients between January
      2006 and December 2011. The indications for endoscopic resection were lesions <=
      10 mm in diameter, confined to the submucosal layer, and without lymph node or
      distant metastasis. Endoscopic resection was accomplished using endoscopic
      mucosal resection (EMR), EMR with a ligation device (EMR-L), EMR after
      circumferential precutting, or endoscopic submucosal dissection (ESD). RESULTS:
      EMR was performed in 18 tumors, EMR-L in 16, EMR after circumferential precutting
      in 3, and ESD in 4. En-bloc resection was performed in 39 tumors (95%), and
      endoscopic complete resection was achieved in 40 (98%); pathological complete
      resection was achieved in 17 tumors (41%). The endoscopic complete resection rate
      did not differ according to the resection method, but the pathological complete
      resection rate was higher for ESD than for EMR and EMR-L. Intraprocedural
      bleeding was noted in five cases, with no occurrence of perforation. Recurrence
      was not observed during the mean follow-up period of 17 months (range 1-53
      months). CONCLUSION: Endoscopic resection appears to be a safe and effective
      treatment for duodenal carcinoid tumors measuring <= 10 mm in diameter and
      confined to the submucosal layer.

PMID- 24117947
TI  - A comparison of microscopic ink characteristics of 35 commercially available
      surgical margin inks.
AB  - OBJECTIVE: To compare microscopic characteristics of commercially available
      surgical margin inks used for surgical pathology specimens. STUDY DESIGN:
      Prospective in vitro study. SAMPLE POPULATION: Thirty-five different surgical
      margin inks (black, blue, green, orange, red, violet, and yellow from 5 different
      manufacturers). METHODS: Inks were applied to uniform, single-source, canine
      cadaveric full-thickness ventral abdominal tissue blocks. Tissue blocks and ink
      manufacturers were randomly paired and each color was applied to a length of the
      cut tissue margin. After drying, tissues were fixed in formalin, and 3 radial
      slices were obtained from each color section and processed for routine histologic
      evaluation, yielding 105 randomly numbered slides with each manufacturer's color
      represented in triplicate. Slides were evaluated by 5 blinded, board-certified
      veterinary anatomic pathologists using a standardized scoring scheme. Statistical
      analyses were performed to evaluate for ink manufacturer effects on scores,
      correlation among different subjective variables, and pathologist agreement.
      RESULTS: Black and blue had the most consistently high scores whereas red and
      violet had the most consistently low overall scores, across all manufacturers.
      All colors tested, except yellow, had statistically significant differences in
      overall scores among individual manufacturers. Overall score was significantly
      correlated to all other subjective microscopic scores evaluated. The average
      Spearman correlation coefficient among the 10 pairwise pathologists overall ink
      scores was 0.60. CONCLUSIONS: There are statistically significant differences in
      microscopic ink characteristics among manufacturers, with a notable degree of
      inter-pathologist agreement.

PMID- 24117948
TI  - Carbon monoxide poisoning and death in a large enclosed ventilated area.
AB  - A 55-year-old man with a medical history of tobacco use suddenly collapsed while
      power washing an empty indoor pool in a hotel. The decedent was transported to
      the local hospital where he was pronounced. A postmortem examination revealed
      atherosclerotic heart disease and bilateral pulmonary edema and congestion. A
      postmortem blood carbon monoxide (CO) level was 27% saturation, and a CO
      performed on hospital admission blood was 49% saturation. CO poisoning is a
      common cause of toxicological morbidity and mortality in the United States. The
      circumstances most often occur in an enclosed environment and may be intentional
      or unintentional. CO poisoning has been reported in open, well-ventilated spaces,
      but rarely results in death. A warning label was present on the engine clearly
      stating the dangers of CO emission. However, there was a false sense of security
      due to the large size of the pool room and the presence of industrial blowers
      that were being used for ventilation. 

PMID- 24117949
TI  - From atretic to perforated: a closer view of pulmonary atresia.
AB  - A 7-day-old male infant with membranous pulmonary atresia and intact ventricular
      septum (PA/IVS) underwent hybrid pulmonary valvotomy. Access was via median
      sternotomy guided by intra-operative epicardial ultrasonography. After puncturing
      the atretic pulmonary valve, a 6 mm Wanda balloon catheter was inflated to dilate
      the atretic valve. Adequate valve movement with antegrade flow was confirmed
      using real time epicardial echocardiography. Intra-operative epicardial
      ultrasonography is an effective tool for guiding PA/IVS during hybrid procedures.
      Epicardial echo imaging provides clear images with excellent quality, helps guide
      the hybrid operation, and prevents the need for the ionizing radiation of
      fluoroscopy. 

PMID- 24117950
TI  - Longer storage of red blood cells is associated with increased in vitro
      erythrophagocytosis.
AB  - BACKGROUND AND OBJECTIVES: Refrigerated storage of red blood cells (RBCs) induces
      numerous changes that may target the cells for erythrophagocytosis following
      transfusion. The influence of storage upon the phagocytosis of unseparated and
      fractionated young and old stored RBCs was investigated using two in vitro
      quantitative phagocytosis assays. MATERIALS AND METHODS: Leucocyte-depleted RBC
      units were sampled at day 1 or 42 of storage. Young and old RBCs were
      fractionated at day 1 by density centrifugation and stored in paediatric packs
      for up to 42 days. RBCs were labelled with the fluorescent dye PKH26 and
      incubated with the human monocytic cell line THP-1. Erythrophagocytosis was
      quantified by flow cytometry and plate fluorometric assays. RESULTS: A higher
      proportion of THP-1 cells phagocytosed RBCs stored for 42 days compared with 1
      day (41% and 24% respectively; P<0.0001). This was associated with an increased
      mean number of RBCs phagocytosed per THP-1 cell (5.2+/-0.6 and 3.3+/-0.2
      respectively; P<0.002). Erythrophagocytosis of fractionated young and old RBCs
      increased with longer storage duration up to 28 days (P<0.05). However, no
      significant differences were observed between erythrophagocytosis of young and
      old RBCs. CONCLUSION: The susceptibility of stored RBCs to erythrophagocytosis
      significantly increased with longer storage time of the RBC units. Storage
      duration of RBCs had a greater influence on in vitro erythrophagocytosis than the
      chronological age of the RBCs at donation.

PMID- 24117951
TI  - A sensitive and specific nanoparticle-assisted PCR assay for rapid detection of
      porcine parvovirus.
AB  - A novel nanoparticle-assisted polymerase chain reaction (nanoPCR) assay to detect
      porcine parvovirus (PPV) is described here. Primers for this assay were designed
      based on the conserved region of the nonstructural protein 1 (NS1) gene of PPV,
      which encodes one of the nonstructural proteins. The sensitivity of the PPV
      nanoPCR assay was measured by using diluted recombinant plasmids in which the PPV
      NS1 gene had been inserted. The detection limit was 5.6 * 10(1) copies MUl(-1)
      for the PPV nanoPCR assay vs 5.6 * 10(3) copies MUl(-1) for conventional PCR
      assay. The results showed that the sensitivity of PPV nanoPCR assay was 100 times
      higher than that of conventional PCR assay. The PPV nanoPCR assay produced 142-bp
      product as expected when amplifying PPV DNA, while produced nothing when
      amplifying the DNA or cDNA of the following viruses: swine encephalomyocarditis
      virus, classical swine fever virus, porcine pseudorabies virus, porcine
      reproductive and respiratory syndrome virus, porcine teschovirus and porcine
      circovirus type II. PPV was detected in 108 of 109 clinical swine samples from
      Heilongjiang, Jilin and Henan provinces using the nanoPCR assay, and the results
      were confirmed by sequencing. SIGNIFICANCE AND IMPACT OF THE STUDY: Nanoparticle
      assisted polymerase chain reaction (nanoPCR) assay is an improved PCR. NanoPCR is
      highly sensitive and specific because the nanofluids formed in the nanobuffer
      have high thermal conductivity, which reduces the time required to reach the
      target temperature. It is more sensitive than conventional PCR, and it could
      detect the cases earlier than conventional PCR. This report describes the first
      application of the highly efficient nanoPCR technology for the detection of
      porcine parvovirus (PPV). The PPV nanoPCR assay will be useful for the detection
      and study of PPV and will also be applicable to improve the detection of other
      viruses.

PMID- 24117952
TI  - Relationship between duration of treatment and oral health in adults with
      intellectual and developmental disabilities.
AB  - The purpose of this study was to evaluate how dental outcomes changed over time
      among subjects with intellectual and developmental disabilities (IDD) who were
      under treatment. This retrospective study included 107 subjects who were treated
      at a Tufts Dental Facilities clinic. Data from each subject were collected at
      three time points: initial visit, midpoint visit, and most recent visit.
      Generalized estimating equations were used to assess the relationship between
      time in treatment and several outcome variables (cooperation level, hygiene
      rating, presence of caries, periodontitis, dental pain, and infection).
      Statistically significant decreases in caries (p < .001) and increases in
      periodontitis (p = .002) were found over time. Associations between time and
      other outcome variables were not statistically significant. The prevalence of
      caries decreased and the prevalence of periodontitis increased over time among
      patients with IDDs receiving regular comprehensive dental care. Even among
      patients under routine maintenance, significant oral health problems remain. 

PMID- 24117953
TI  - Cloning and in vitro function analysis of codon-optimized FatI gene.
AB  - Currently, n-3 polyunsaturated fatty acids (n-3 PUFAs) have attracted great
      attention because of their biological significance to organisms. In addition,
      PUFAs show an obvious impact on prevention and treatment of various diseases.
      Because n-3 PUFAs cannot be endogenously synthesized by mammals, mammals have to
      rely on a dietary supplement for sufficient supply. The finding and application
      of the fatty acid dehydrogenase I (FatI) gene are expected to change the current
      situation because it can convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n
      3 PUFAs. Meanwhile, the gradual maturation of transgenic technology makes it
      possible to produce transgenic animals that can synthesize n-3 PUFAs by
      themselves. In this study, the DNA coding sequence of FatI was synthesized by a
      chemical method after codon optimization according to the mammal's codon bias.
      The synthesized DNA sequence was introduced into Boer goat fetal fibroblasts by
      the constructed recombinant eukaryotic expression vector pcDNA3.1(+)-FatI. Boer
      goat fetal fibroblasts were transfected by electroporation, and the stable
      transfected cell lines were obtained by G418 selection. Genomic DNA PCR and
      Southern blot were applied to verify that the foreign gene FatI was integrated
      into the genome of the Boer goat fibroblasts. RT-PCR results showed the
      expression of FatI gene at the mRNA level. The fatty acid profile of cells
      carrying the FatI gene revealed an increase in total n-3 PUFAs (from 0.61 to
      0.95), but a decrease in n-6 PUFAs (from 10.34 to 9.85), resulting in a
      remarkable increase in the n-3:n-6 ratio (from 0.059 to 0.096). The n-3:n-6 ratio
      had a 63.49 percent increase, which is a precursor of the response of n-3
      desaturase activity of the FatI gene. The study may provide a practical tool for
      producing transgenic animals that can produce n-3 PUFAs by themselves, and we
      hope that the application will lay the foundation for animals producing n-3
      PUFAs, which will benefit human nutrition and wellness. 

PMID- 24117954
TI  - Modeling transcriptional networks regulating secondary growth and wood formation
      in forest trees.
AB  - The complex interactions among the genes that underlie a biological process can
      be modeled and presented as a transcriptional network, in which genes (nodes) and
      their interactions (edges) are shown in a graphical form similar to a wiring
      diagram. A large number of genes have been identified that are expressed during
      the radial woody growth of tree stems (secondary growth), but a comprehensive
      understanding of how these genes interact to influence woody growth is currently
      lacking. Modeling transcriptional networks has recently been made tractable by
      next-generation sequencing-based technologies that can comprehensively catalog
      gene expression and transcription factor-binding genome-wide, but has not yet
      been extensively applied to undomesticated tree species or woody growth. Here we
      discuss basic features of transcriptional networks, approaches for modeling
      biological networks, and examples of biological network models developed for
      forest trees to date. We discuss how transcriptional network research is being
      developed in the model forest tree genus, Populus, and how this research area can
      be further developed and applied. Transcriptional network models for forest tree
      secondary growth and wood formation could ultimately provide new predictive
      models to accelerate hypothesis-driven research and develop new breeding
      applications. 

PMID- 24117955
TI  - Fibrinogen as a therapeutic target for bleeding: a review of critical levels and
      replacement therapy.
AB  - Fibrinogen plays a critical role in achieving and maintaining hemostasis and is
      fundamental to effective clot formation. There is increasing awareness of the
      important role of fibrinogen as a key target for the treatment and prevention of
      acquired bleeding. Fibrinogen is the first coagulation factor to fall to
      critically low levels (<1.0 g/L) during major hemorrhage (normal plasma
      fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend
      maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation
      can be achieved using plasma or cryoprecipitate; however, there are a number of
      safety concerns associated with these allogeneic blood products and there is a
      lack of high-quality evidence to support their use. Additionally, there is
      sometimes a long delay associated with the preparation of frozen products for
      infusion. Fibrinogen concentrate provides a promising alternative to allogeneic
      blood products and has a number of advantages: it allows a standardized dose of
      fibrinogen to be rapidly administered in a small volume, has a very good safety
      profile, and is virally inactivated as standard. Administration of fibrinogen
      concentrate, often guided by point-of-care viscoelastic testing to allow
      individualized dosing, has been successfully used as hemostatic therapy in a
      range of clinical settings, including cardiovascular surgery, postpartum
      hemorrhage, and trauma. Results show that fibrinogen concentrate is associated
      with a reduction or even total avoidance of allogeneic blood product transfusion.
      Fibrinogen concentrate represents an important option for the treatment of
      coagulopathic bleeding; further studies are needed to determine precise dosing
      strategies and thresholds for fibrinogen supplementation. 

PMID- 24117956
TI  - Eruptive dermal clear cell desmo-plastic mesenchymal tumors with perivascular
      myoid differentiation in a young boy. A clinical, histopathologic,
      immunohistochemical and electron microscopy study of 17 lesions.
AB  - Clear cell tumors of the skin are observed in a wide variety of benign and
      malignant conditions with different histogenesis, sharing the presence of cells
      with abundant clear cytoplasm. Herein, we report the clinicopathologic features
      of a healthy young patient affected by asymptomatic, eruptive and disseminated,
      benign clear cell dermal tumors since early infancy. Neither family history nor
      genetic testing and counseling provided further useful information. The lesions
      were mostly confined to the face and lower left extremity with pink
      teleangiectatic papules and small nodules. Over a 4-year period, a total of 16
      different cutaneous lesions were biopsied and histopathologic and
      immunohistochemical studies carried out; an additional lesion was also removed
      for electron microscopy examination. Histopathology evidenced multiple
      perivascular growths of spindle to oval and round cells intermingled with
      clear/granular cells throughout the dermis, with prominent desmoplasia and
      numerous capillary-like vessels with focal hemangiopericytoma-like features.
      Immunohistochemical neoplastic cells were uniformly positive for h-caldesmon and
      focally smooth muscle alpha-actin and CD13 indicating myoid differentiation
      whereas the consistent diffuse cytoplasmic staining for lysosome antigen, such as
      CD68PG-M1 and NKI/C3 along with the ultrastructural findings supported the view
      of a lysosome-mediated apoptotic process. The differential diagnosis with other
      clear cell cutaneous neoplasms is discussed.

PMID- 24117957
TI  - Inhibitory effects of ammonia on methanogen mcrA transcripts in anaerobic
      digester sludge.
AB  - Methanogens in anaerobic ammonia-rich digesters show differential responses to
      ammonia stress. The mechanism for this is poorly understood. In the present
      study, we determined the rates of methane production, the composition of
      methanogen mcrA (the gene coding for the alpha subunit of methyl-coenzyme M
      reductase) and their transcripts in response to ammonium addition in the
      anaerobic sludge retrieved from a full-scale digester treating swine manure. The
      rate of CH4 production substantially reduced with increased addition of ammonium.
      The analysis of natural (13)C abundances of CH4 and CO2 indicated that the
      aceticlastic methanogenesis was more sensitive than hydrogenotrophic
      methanogenesis. Quantitative PCR analysis revealed that mcrA copy number
      decreased by one order of magnitude in the treatment with a large amount of
      ammonium (10 g NH4+-N L(-1)) but did not change much with treatments of smaller
      amounts (3 and 7 g NH4+-N L(-1)) compared with the control. T-RFLP analysis of
      mcrA compositions showed that the structure of the methanogen community remained
      highly stable, with Methanosaetaceae dominating the methanogen community in all
      incubations. The composition of mcrA transcripts, however, showed a substantial
      response to the addition of ammonium. The relative abundance of Methanosaetaceae
      transcripts declined with increasing amounts of ammonium, whereas the transcript
      level of Methanobacteriales mcrA was relatively resistant. The differential
      responses corresponded to the shift of methanogenic pathway inferred from (13)C
      isotope fractionation. Our study suggests that methanogens in anaerobic sludge
      have a strong mcrA transcriptional response to ammonia stress without a change in
      the community structure.

PMID- 24117958
TI  - Children with multiple viral respiratory infections are older than those with
      single viruses.
AB  - AIM: To study the clinical impact of multiple viral respiratory infections
      compared to single infections. METHODS: Demographic data from 37 multiple
      infection periods in children <5 years of age were compared to data from 193
      episodes with single infections. Clinical data derived from patient records of
      the multiple infection episodes were further compared to data from 93 matched
      control episodes with single infections. RESULTS: The mean age of patients with
      multiple viral findings was 12.7 months, compared to 5.7 months for those with
      single findings (p < 0.01). Wheezing was the most common diagnosis in both
      groups, except among children who were only infected with the coronavirus. No
      differences were found regarding duration of hospitalisation, oxygen treatment or
      admittance to the intensive care unit. CONCLUSION: Children with multiple viral
      findings in their respiratory secretions were older than those with a single
      detected virus. Otherwise, no major differences in comorbidity, presentation or
      clinical outcome were observed between the two groups.

PMID- 24117959
TI  - Recognition of objects in simulated irregular phosphene maps for an epiretinal
      prosthesis.
AB  - Visual prostheses offer a possibility of restoring vision to the blind. It is
      necessary to determine minimum requirements for daily visual tasks. To
      investigate the recognition of common objects in daily life based on the
      simulated irregular phosphene maps, the effect of four parameters (resolution,
      distortion, dropout percentage, and gray scale) on object recognition was
      investigated. The results showed that object recognition accuracy significantly
      increased with an increase of resolution. Distortion and dropout percentage had
      significant impact on the object recognition; with the increase of distortion
      level and dropout percentage, the recognition decreased considerably. The
      accuracy decreased significantly only at gray level 2, whereas the other three
      gray levels showed no obvious difference. The two image processing methods
      (merging pixels to lower the resolution and edge extraction before lowering
      resolution) showed significant difference on the object recognition when there
      was a high degree of distortion level or dot dropout. 

PMID- 24117960
TI  - Mastoid triangle for sex determination in adult Nigerian population: a validation
      study.
AB  - In the quest for a simple, reliable technique to estimate the sex of human
      remains several novel metric skeletal indices have been reported. Only a few have
      been examined for utility in populations different from those in which they were
      developed. In this study, the mastoid process was evaluated for sex determination
      using 102 lateral cephalograms of a Nigerian sample of known age and sex. The
      asterion-mastoidale distance and mastoid triangular area were sexually dimorphic
      with mean values higher in males compared with females (p = 0.02). On analysis of
      the discriminant function, overall accuracy for sex classification was 55%. On
      cross-validation, the triangular area accurately identified 80% of females and
      48% of males. The asterion-mastoidale distance was slightly more accurate at
      sexing the sample. The practical utility of the mastoid triangle area technique
      to differentiate sex in Nigerian populations is not supported by the results of
      this study.

PMID- 24117961
TI  - Does among-population variation in burst swimming performance of sockeye salmon
      Oncorhynchus nerka fry reflect early life migrations?
AB  - Using a fixed-speed test, burst swimming performance was found to vary among nine
      populations of emergent sockeye salmon Oncorhynchus nerka fry reared in a common
      garden environment. No consistent relationship was, however, detected between
      difficulty of fry migration (upstream v. downstream) to rearing areas and total
      burst swimming duration or bursting rate. 

PMID- 24117962
TI  - Early changes, attrition, and dose-response in low intensity psychological
      interventions.
AB  - OBJECTIVES: To investigate if early symptom changes in brief low intensity
      psychological interventions (guided self-help and psycho-education using
      cognitive behavioural therapy principles) are predictive of final treatment
      outcome. DESIGN: Retrospective cohort data analysis. METHOD: Clinical records for
      1,850 patients who screened positive for depression and/or an anxiety disorder
      were analysed. Reliable and clinically significant improvement (RCSI) on
      depression (Patient Health Questionnaire-9: PHQ-9) or anxiety (generalized
      anxiety disorder-7: GAD-7) outcome measures after treatment was the primary
      outcome. Change scores >=6 on PHQ-9 and >=5 on GAD-7 were taken as indicative of
      reliable improvement (RI). The model assumed that RI in the earliest treatment
      sessions would be predictive of RCSI post-treatment. Predictive accuracy was
      assessed by calculating the area under the curve (AUC), as well as positive and
      negative predictive values. Diagnostic odds ratios were also estimated, adjusting
      for confounders such as baseline severity, use of medication, and pre-treatment
      symptom change. RESULTS: The AUC estimates for session-to-session change scores
      ranged between .62 and .88, indicative of modest to high predictive reliability.
      Predictive accuracy was higher for patients who had four or more treatment
      sessions, with more than 70% of patients with RCSI being accurately identified as
      early as sessions 1-3. Attrition rates were significantly associated with poor
      outcomes. Results suggest that at least four therapy sessions are necessary to
      achieve more than 50% RCSI rates, and the dose-response effect appears to decline
      in treatments longer than six sessions. CONCLUSIONS: Patients showing RI early in
      treatment were at least twice as likely to fully recover compared to those
      without early RI.

PMID- 24117963
TI  - Lymphoepithelioma-like carcinoma of the penis: association with human papilloma
      virus infection.

PMID- 24117964
TI  - Maternal pre-pregnancy body mass index and risk of selected birth defects:
      evidence of a dose-response relationship.
AB  - BACKGROUND: This study investigates the relationship between maternal pre
      pregnancy body mass index (BMI) and 26 birth defects identified through the
      Florida Birth Defects Registry. METHODS: Pre-pregnancy BMI (kg/m(2)) was
      categorised into underweight (<18.5), normal weight (18.5-24.9), overweight (25.0
      29.9), and obese (>=30.0) among Florida resident mothers without pre-gestational
      diabetes who gave birth to singleton infants from March 2004 through December
      2009. Obesity was classified as obese I (30.0-34.9), obese II (35.0-39.9), and
      obese III (>=40.0). Logistic regression was used to calculate the adjusted odds
      ratios and 95% confidence interval, representing the association between pre
      pregnancy BMI and each of the 26 specific birth defects (and an 'any birth
      defect' composite). Models were adjusted for maternal age, race/ethnicity,
      education, smoking, marital status, and nativity. RESULTS: The livebirth
      prevalence of any birth defect increased with increasing BMI, from 3.9% among
      underweight women to 5.3% among obese III women (P < 0.001). Results show a
      direct dose-response relationship between maternal pre-pregnancy BMI and 10
      defects under study (cleft palate without cleft lip, diaphragmatic hernia,
      hydrocephalus without spina bifida, hypoplastic left heart syndrome, pulmonary
      valve atresia and stenosis, pyloric stenosis, rectal and large intestinal
      atresia/stenosis, transposition of great arteries, tetralogy of Fallot, and
      ventricular septal defects) and the 'any birth defect' category. Conversely,
      gastroschisis exhibited a statistically significant inverse relationship with pre
      pregnancy BMI. CONCLUSIONS: This study provides evidence of the increasing risk
      of birth defect-affected pregnancy with increasing pre-pregnancy obesity.
      Reducing pre-pregnancy obesity, even among obese women, may reduce the occurrence
      of birth defects.

PMID- 24117965
TI  - Influence of melatonin receptor signalling on parameters involved in blood
      glucose regulation.
AB  - The pineal hormone melatonin is known to influence insulin secretion via the G
      protein-coupled receptor isoforms MT1 and MT2. The present study was aimed to
      further elucide the impact of melatonin on blood glucose regulation. To this end,
      mouse lines were used, in which one of the two or both melatonin receptors were
      deleted. In comparison with wild-type mice of the same age (8-12 months old),
      increased plasma insulin and melatonin levels and decreased blood glucose levels
      and body weights were detected in the MT1- and double-knockout lines. The
      elimination of melatonin receptor signalling also altered blood glucose
      concentrations, body weight and melatonin and insulin levels when comparing wild
      type and receptor knockout mice of different ages (6 wk and 8-12 months old);
      such changes, however, were dependent on the type of receptor deleted.
      Furthermore, reverse transcription polymerase chain reaction results provided
      evidence that melatonin receptor deficiency has an impact on transcript levels of
      pancreatic islet hormones as well as on pancreatic and hepatic glucose
      transporters (Glut1 and 2). Under stimulated insulin secretion in the presence of
      melatonin in the rat insulinoma beta-cells INS-1, the Glut1 transcript level was
      decreased. In conclusion, the present findings demonstrate that melatonin
      receptor knockout types affect blood glucose levels, body weight, plasma levels
      of melatonin and insulin, as well as pancreatic hormone and Glut1 expression in
      significantly different manners.

PMID- 24117966
TI  - Rarely metastasizing soft tissue tumours.
AB  - Soft tissue tumours that rarely metastasize have been afforded their own
      subcategory in recent WHO classifications. This review discusses the nature of
      these tumours and the difficulty in constructing usefully simple classifications
      for heterogeneous and complex groups of tumours. We also highlight the specific
      rarely metastasizing soft tissue tumours that have been recently added to the WHO
      classification (phosphaturic mesenchymal tumour, pseudomyogenic
      haemangioendothelioma) and those entities where there have been recent important
      defining genetic discoveries (myxoinflammatory fibroblastic sarcoma, solitary
      fibrous tumour, myoepitheliomas). 

PMID- 24117967
TI  - Transjugular intrahepatic portosystemic shunt in combination with or without
      variceal embolization for the prevention of variceal rebleeding: a meta-analysis.
AB  - BACKGROUND AND AIM: Transjugular intrahepatic portosystemic shunt (TIPS) is the
      mainstay treatment option for the complications of portal hypertension. Whether
      or not variceal embolization should be performed during TIPS procedures remains
      controversial. A meta-analysis to compare the incidence of shunt dysfunction,
      variceal rebleeding, encephalopathy, and death between patients treated with TIPS
      alone and those treated with TIPS combined with variceal embolization was
      conducted. METHODS: All relevant studies were searched via PubMed, EMBASE, and
      Cochrane Library databases. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were pooled. Heterogeneity among studies and publication bias were assessed.
      RESULTS: Six articles were included in our study. Type of stents was covered (n =
      2), bare (n = 2), mixed (n = 1), and unknown (n = 1). Varices were
      angiographically embolized by coils in six studies. Additional liquids agents
      were employed in three studies. Compared with TIPS alone group, TIPS combined
      with variceal embolization group had a significantly lower incidence of variceal
      rebleeding (OR 2.02, 95% CI 1.29-3.17, P = 0.002), but a similar incidence of
      shunt dysfunction (OR 1.26, 95% CI 0.76-2.08, P = 0.38), encephalopathy (OR 0.81,
      95% CI 0.46-1.43, P = 0.47), and death (OR 0.90, 95% CI 0.55-1.47, P = 0.68).
      Neither any significant heterogeneity nor proof of publication bias among studies
      was found in all meta-analyses. CONCLUSIONS: Adjunctive variceal embolization
      during TIPS procedures might be beneficial in the prevention of variceal
      rebleeding. However, given the heterogeneity of type of stents, embolic agents,
      type of varices, and indications of variceal embolization among studies,
      additional well-designed randomized, controlled trials with larger sample size
      and use of covered stents should be warranted to confirm these findings.

PMID- 24117968
TI  - Protective effects of fish omega-3 fatty acids on doxorubicin-induced testicular
      apoptosis and oxidative damage in rats.
AB  - The aim of this study was to examine the protective effects of fish omega-3 (n-3)
      fatty acids on acute doxorubicin (DOX)-induced testicular apoptosis and oxidative
      damage. 24 male rats were divided into three groups: control, DOX-treated and
      DOX+fish n-3 fatty acids. Fish n-3 fatty acids (400 mg kg(-1) ) were given for 30
      days by intragastric gavage. The rats received a single intraperitoneal injection
      of DOX (30 mg kg(-1) ) and were sacrificed after 48 h. The DOX+fish n-3 fatty
      acids group showed a decrease in malondialdehyde levels and increased activities
      of superoxide dismutase and glutathione peroxidase in comparison with the DOX
      treated group. Acute DOX treatment caused severe damage such as disorganisation
      and separation of germ cells. The fish n-3 fatty acids-pretreated rats showed an
      improved histological appearance in the DOX-treated group. Our data indicate a
      reduction in the activity of terminal deoxynucleotidyl transferase mediated dUTP
      nick end labelling; there was a rise in the expression of proliferating cell
      nuclear antigen in testis tissues of the DOX+fish n-3 fatty acids group compared
      with DOX-treated group. These data suggested that fish n-3 fatty acids pre
      treatment may be beneficial for spermatogenesis following acute DOX-induced
      testicular damage by decreasing germ cell apoptosis and oxidative stress.

PMID- 24117969
TI  - EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule
      regulates growth cone repulsion through ADAM10 metalloprotease.
AB  - EphrinA/EphA-dependent axon repulsion is crucial for synaptic targeting in
      developing neurons but downstream molecular mechanisms remain obscure. Here, it
      is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion
      molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10
      to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced
      ADAM10 activity to promote ectodomain shedding of polysialic acid-NCAM in
      cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of
      most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3
      kinase activity as shown in HEK293T cells transfected with dominant negative
      ADAM10 and kinase-inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at
      a sequence within the E-F loop of the second fibronectin type III domain
      (Leu(671) -Lys(672) /Ser(673) -Leu(674) ) identified by mass spectrometry.
      Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3-induced
      shedding of NCAM in HEK293T cells. EphrinA5-induced growth cone collapse was
      dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null
      mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM.
      Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely
      impacts synapse development, and may lead to excess NCAM shedding when disrupted,
      as implicated in neurodevelopmental disorders such as schizophrenia. PSA-NCAM and
      ephrinA/EphA3 coordinately regulate inhibitory synapse development. Here, we have
      found that ephrinA5 stimulates EphA3 kinase and ADAM10 activity to promote PSA
      NCAM cleavage at a site in its second FNIII repeat, which regulates ephrinA5
      induced growth cone collapse in GABAergic and non-GABAergic neurons. These
      findings identify a new regulatory mechanism which may contribute to inhibitory
      connectivity.

PMID- 24117970
TI  - Level of asthma control and healthcare utilization in Latin America.
AB  - The purpose of this study was to investigate whether uncontrolled asthma was
      associated with healthcare outcomes among Latin American patients with asthma. We
      used data from 2168 patients with asthma who participated in the 2011 Latin
      America Asthma Insights and Management (AIM) survey. Using Global Initiative for
      Asthma (GINA) guidelines, patients were categorized as having asthma that was
      well-controlled, partly controlled, or uncontrolled. Overall, 7% of the patients
      surveyed had asthma that was classified as well-controlled. Patients whose asthma
      was not well-controlled were significantly more likely to report use of asthma
      medications (ORs ranging from 1.6-41) and to have had emergency healthcare visits
      or hospitalizations for their asthma in the previous year (ORs ranging from 2.1
      to 5.9). They also reported decreases in their productivity compared to patients
      with well-controlled asthma. These associations suggest that emphasis on
      improving asthma control could have substantial effects on patient productivity
      and utilization of healthcare resources. 

PMID- 24117971
TI  - Robust anti-oxidant defences in the rice blast fungus Magnaporthe oryzae confer
      tolerance to the host oxidative burst.
AB  - Plants respond to pathogen attack via a rapid burst of reactive oxygen species
      (ROS). However, ROS are also produced by fungal metabolism and are required for
      the development of infection structures in Magnaporthe oryzae. To obtain a better
      understanding of redox regulation in M. oryzae, we measured the amount and redox
      potential of glutathione (E(GSH)), as the major cytoplasmic anti-oxidant, the
      rates of ROS production, and mitochondrial activity using multi-channel four
      dimensional (x,y,z,t) confocal imaging of Grx1-roGFP2 and fluorescent reporters
      during spore germination, appressorium formation and infection. High levels of
      mitochondrial activity and ROS were localized to the growing germ tube and
      appressorium, but E(GSH) was highly reduced and tightly regulated during
      development. Furthermore, germlings were extremely resistant to external H2O2
      exposure ex planta. EGSH remained highly reduced during successful infection of
      the susceptible rice cultivar CO39. By contrast, there was a dramatic reduction
      in the infection of resistant (IR68) rice, but the sparse hyphae that did form
      also maintained a similar reduced E(GSH). We conclude that M. oryzae has a robust
      anti-oxidant defence system and maintains tight control of EGSH despite
      substantial oxidative challenge. Furthermore, the magnitude of the host oxidative
      burst alone does not stress the pathogen sufficiently to prevent infection in
      this pathosystem.

PMID- 24117972
TI  - First report of viral nervous necrosis-induced mass mortality in hatchery-reared
      larvae of clownfish, Amphiprion sebae Bleeker.
AB  - Frequent mortality was observed in the larval rearing facility of marine
      clownfish, Amphiprion sebae Bleeker. Mortality resulted in 80% loss of larval
      stock. Moribund larvae showed clinical signs typical of viral nervous necrosis,
      such as uncoordinated, corkscrew-like swimming behaviour, hypersensitivity to
      stimuli, darkening of body and assembly into large groups, similar to bunches of
      grapes. The aetiology of the disease was confirmed by gross observation of
      clinical signs, histopathology and molecular diagnosis. Histological studies
      revealed severe vacuolation in the brain and in the bipolar and ganglion layers
      of the eye. Molecular diagnosis by reverse transcription-polymerase chain
      reaction (RT-PCR) specific to piscine nodavirus yielded a positive result. The
      partial nucleotide sequences of the PCR-amplified fragment were 97-98% similar to
      other betanodavirus isolates reported globally and more closely aligned with red
      spotted grouper nervous necrosis virus (RGNNV). This is the first report of
      susceptibility of clownfish, A. sebae, to betanodavirus and the presence of the
      RGNNV in India. 

PMID- 24117973
TI  - Phenotypic traits, virulence-associated gene profile and genetic relatedness of
      Edwardsiella tarda isolates from Japanese eel Anguilla japonica in Korea.
AB  - Edwardsiella tarda is the predominant bacterium in farm-cultured eel in Korea.
      Here, we evaluated the heterogeneity of 37 E. tarda isolates derived from
      Japanese eel with various origins (olive flounder, common carp and ornamental
      fish) between 2003 and 2010. Regardless of origins, the biochemical
      characteristics of E. tarda isolates were homogenous except hydrogen sulfide
      production, citrate utilization and mannitol fermentation. Based on the
      phylogenetic analysis of 16S rRNA, E. tarda isolates could be classified into two
      subgroups and displayed a close relation with Edwardsiella ictaluri and
      Edwardsiella hosinae lineages, suggesting that the subgroup I has been a
      predominant type in the Jeonnam and Jeonbuk provinces. I-CeuI-based pulsed-field
      gel electrophoresis (PFGE) typing showed that the isolates from Japanese eels
      belonged to 11 pulsotypes, indicating that the presence of highly genomic
      diversity. Additionally, two isolates, ET-060 and ET-191, showed a high frequency
      of virulence genes (100%) and caused 90% and 60% mortality in Japanese eel,
      respectively. This finding suggests a substantial congruence of virulence gene
      profiles and pathogenicity. Our results demonstrate that the intraspecific
      diversity within E. tarda strains from Japanese eel has been in prior existence.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the biochemical characteristics,
      the phylogenetic property of the 16S rRNA gene and PFGE types of Edwardsiella
      tarda, we could identify the intraspecific diversity of isolates from Japanese
      eel, Anguilla japonica in Korea. In addition, this study describes the strong
      congruence of virulence-related genes and pathogenicity, suggesting that the
      virulence profile may be useful tool for prediction of pathogenicity.

PMID- 24117974
TI  - Incremental value of three-dimensional transthoracic echocardiography in the
      assessment of ruptured aneurysm of anterior mitral leaflet.
AB  - The mitral valve aneurysm is a rare complication of infective endocarditis
      involving mitral or aortic valve. The perforation of the mitral valve aneurysm
      can lead to significant mitral regurgitation (MR) or thromboembolism, which can
      cause sudden hemodynamic deterioration. We describe here a case of healed
      infective endocarditis of the aortic valve with ruptured mitral valve aneurysm
      that led to severe MR. The aneurysm of the anterior mitral leaflet was diagnosed
      by two-dimensional transthoracic echocardiography. In this case, three
      dimensional transthoracic echocardiography demonstrated the detailed morphology
      of mitral valve aneurysm which resulted in successful surgical repair of the
      aneurysm. 

PMID- 24117975
TI  - Early fresh-frozen plasma transfusion decreases the risk of retinopathy of
      prematurity.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 (IGFBP
      3) play a main role in the pathogenesis of retinopathy of prematurity (ROP).
      Fresh-frozen plasma (FFP) from adult donors may be an actual source of IGF-1 and
      IGFBP-3 because it contains higher concentrations. The objective was to evaluate
      whether FFP transfusions can decrease the occurrence of ROP in a cohort of
      preterm infants. STUDY DESIGN AND METHODS: We retrospectively analyzed data from
      218 infants with gestational age of less than 29 weeks who either received FFP or
      did not and correlated this procedure to the development of any grade of ROP.
      RESULTS: Logistic regression analysis demonstrated that two or more transfusions
      of FFP was effective in decreasing the risk of development of any grade of ROP
      (relative risk, 0.46; 95% confidence interval, 0.23-0.93). Other factors that
      affected the risk of ROP were gestational age, birthweight, antenatal steroid
      treatment, FiO2  of at least 0.40, mechanical ventilation, and sepsis.
      CONCLUSIONS: We found that two or more transfusions of FFP in the first week of
      life decrease the risk of developing any grade of ROP in preterm infants with
      gestational age of less than 29 weeks.

PMID- 24117976
TI  - Population pharmacokinetic/pharmacodynamic modelling of eltrombopag in healthy
      volunteers and subjects with chronic liver disease.
AB  - AIMS: To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of
      eltrombopag in chronic liver disease (CLD). METHODS: The PK/PD model was
      developed using data from 79 CLD patients using nonlinear mixed-effects
      modelling. RESULTS: The PK of eltrombopag were described by a two-compartment
      model with dual sequential first-order absorption. Gender, race and severity of
      CLD were predictors of the apparent clearance of eltrombopag. The PD of
      eltrombopag in CLD were adequately described by a four-compartment lifespan
      model, in which eltrombopag stimulated platelet precursor production rate. East
      Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag.
      Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak
      platelet counts was longer for the CLD population compared with patients who had
      immune thrombocytopenic purpura, but was comparable to patients with hepatitis C.
      Likewise, it took a longer time for platelet counts to rebound back to baseline
      once eltrombopag treatment was discontinued. CONCLUSIONS: The time course of the
      platelet response in CLD was different from that in immune thrombocytopenic
      purpura but comparable to that in hepatitis C.

PMID- 24117977
TI  - The teeth and faces of twins: providing insights into dentofacial development and
      oral health for practising oral health professionals.
AB  - The continuing studies of the teeth and faces of Australian twins and their
      families in the Craniofacial Biology Research Group in the School of Dentistry at
      the University of Adelaide began 30 years ago. Three main cohorts of twins have
      been recruited, enabling various objectives and specific hypotheses to be
      addressed about the roles of genetic, epigenetic and environmental influences on
      human dentofacial growth and development, as well as oral health. This paper
      highlights some key findings arising from these studies, emphasizing those of
      direct relevance to practising oral health professionals. We also draw on
      published literature to review the significant developments in relation to the
      use of precision 2D and 3D imaging equipment, the application of modern molecular
      techniques, and the development of sophisticated computer software for analysing
      genetic relationships and comparing complex shapes. Such developments are
      valuable for current and future work. Apart from the classical or traditional
      twin model, there are several other twin models that can be used in research to
      clarify the relative contributions of genetic, epigenetic and environmental
      contributions to phenotypic variation. The monozygotic (MZ) co-twin model is one
      particularly valuable method, given that examination of only one pair of MZ twins
      can provide considerable insights into underlying causes of observed variation.
      This model can be used in a dental practice environment, with oral health
      professionals having the opportunity to explore differences in orofacial
      structures between MZ co-twins who are attending as patients. As researchers have
      become more aware of the complexities of the interactions between the genome, the
      epigenome and the environment during development, there is the need to collect
      more phenotypic data and define new phenotypes that will better characterize
      variations in growth processes and health status. When coupled with powerful new
      genetic approaches, including genome-wide association studies and linkage
      analyses, exciting opportunities are opening up to unravel the causes of problems
      in craniofacial growth and common oral diseases in human populations.

PMID- 24117978
TI  - Craniofacial and dental manifestations of triple X syndrome associated with
      congenital hypothyroidism: a case report.
AB  - Triple X syndrome (47,XXX) is a numerical chromosomal alteration that affects
      1/1,000 women, in which the woman is born with an extra X chromosome. Some oral
      changes have been reported in the literature, as hypodontia, influence on
      deposition of crown enamel and discrepancies in cephalometric measurements. Other
      systemic complications may lead to oral abnormalities similar to those seen in
      triple X patients, such as congenital hypothyroidism (CH). This paper reports a
      triple X syndrome case associated with CH later treated. Besides delay in
      cognitive and intellectual development, the patient had changes in teeth
      development and in cephalometric measurements with deficiencies in the maxilla
      and mandible. This is the first report of a triple X syndrome associated with CH.
      Both conditions may result in changes in dentofacial development. 

PMID- 24117979
TI  - Evaluation of crural release and ischial osteotomy for relief of tension in the
      repair of large segmental urethral defects in male cats.
AB  - OBJECTIVE: To examine if the tension at the site of a urethral anastomosis can be
      relieved by performing either a crural release technique or an ischial osteotomy
      technique. STUDY DESIGN: Cadaveric study and 2 case reports. ANIMALS: Adult male
      cat cadavers (n = 18). METHODS: Cats were divided into 2 groups; crural release
      (n = 9) and ischial osteotomy (n = 9). In each group, 20%, 25%, and 30% of the
      pelvic urethra was excised in 3 cats. The length of the urethral defect was
      measured after excision of the urethral segment, and after approximation, before
      and subsequent to the tension relieving technique performed. Two clinical cases
      are described. RESULTS: Both crural release and ischial osteotomy were effective
      in relieving the tension encountered at the urethral anastomosis after removal of
      20% of the urethral length. In the ischial osteotomy group, apposition without
      tension after removing up to 30% of the intrapelvic urethral length was easily
      achieved. A similar technique was successfully used in 2 clinical cases.
      CONCLUSION: Crural release and ischial osteotomy techniques allow approximation
      and tension free anastomosis of large segmental defects of the pelvic urethra in
      cats.

PMID- 24117980
TI  - Egoistic and moralistic self-enhancement in the eye of the beholder: a cross
      informant study.
AB  - This study was conceived to assess the agreement between self- and other reports
      of egoistic (E) and moralistic (M) self-enhancement (SE). A self-report scale
      assessing E-SE and M-SE was filled out by 304 participants (mean age = 39.11, SD
      = 10.12, 54% female). The scale, with items worded in third person, was also
      completed by 304 informants (one for each target participant). Data were
      subjected to a correlated-traits correlated-methods model. Confirmatory factor
      analysis yielded two distinct factors for both self- and other ratings of E-SE
      and M-SE. A significant correlation across raters was observed for each factor.
      Proportion of trait variance was .58 for E-SE and .35 for M-SE. Proportion of
      method variance was .24 and .41, respectively. E-SE and M-SE were substantially
      correlated within each data source. However, the two measures became orthogonal
      after method variance was partialed out. Measures of E-SE and M-SE include both
      trait and artifactual components of variance, which are likely to reflect
      individual differences in the style of self-presentation and response bias (i.e.,
      tendencies to exaggerate agentic and communal qualities). The trait components of
      E-SE and M-SE represent two unrelated tendencies that can be captured and
      distinguished not only through self-judgments, but also by an external observer.

PMID- 24117981
TI  - Perineural inflammation in morphea (localized scleroderma): systematic
      characterization of a poorly recognized but potentially useful histopathological
      feature.
AB  - The association between morphea and perineural inflammation has been reported
      sporadically but never studied systematically. To assess the prevalence and
      nature of perineural inflammation in various clinicopathologic stages of morphea
      and a cohort of other inflammatory dermatoses, 80 morphea and 36 control skin
      biopsies were studied using hematoxylin/eosin and S100 stains. Perineural
      inflammation was semiquantitatively analyzed (scored), which along with the
      pattern (concentric vs. marginal) and cellular composition was compared in the
      two groups. Perineural inflammation was identified in 84% and 61% of morphea and
      control cases, respectively. Examination of only routinely stained sections could
      still detect this feature in 58% of morphea and 33% of control biopsies. Mean
      perineural inflammation score in morphea (0.65) was significantly higher than in
      the control group (0.23) (p < 0.0001) and the inflammation tended to show a
      concentric pattern with plasma cell neurotropism. Intraneural inflammation was
      limited to four morphea cases. Although perineural inflammation is common in
      morphea, it is not unusual to find this feature in other inflammatory conditions.
      Nevertheless, perineural inflammation can serve as an important diagnostic
      adjunct in difficult cases of morphea if one considers its greater intensity,
      predominantly concentric pattern and the tendency to show plasma cell
      neurotropism. 

PMID- 24117982
TI  - Exploring links between pH and bacterial community composition in soils from the
      Craibstone Experimental Farm.
AB  - Soil pH is an important determinant of microbial community composition and
      diversity, yet few studies have characterized the specific effects of pH on
      individual bacterial taxa within bacterial communities, both abundant and rare.
      We collected composite soil samples over 2 years from an experimentally
      maintained pH gradient ranging from 4.5 to 7.5 from the Craibstone Experimental
      Farm (Craibstone, Scotland). Extracted nucleic acids were characterized by
      bacterial and group-specific denaturing gradient gel electrophoresis and next
      generation sequencing of bacterial 16S rRNA genes. Both methods demonstrated
      comparable and reproducible shifts within higher taxonomic bacterial groups (e.g.
      Acidobacteria, Alphaproteobacteria, Verrucomicrobia, and Gammaproteobacteria)
      across the pH gradient. In addition, we used non-negative matrix factorization
      (NMF) for the first time on 16S rRNA gene data to identify positively interacting
      (i.e. co-occurring) operational taxonomic unit (OTU) clusters (i.e.
      'components'), with abundances that correlated strongly with pH, and sample year
      to a lesser extent. All OTUs identified by NMF were visualized within principle
      coordinate analyses of UNIFRAC distances and subjected to taxonomic network
      analysis (SSUnique), which plotted OTU abundance and similarity against
      established taxonomies. Most pH-dependent OTUs identified here would not have
      been identified by previous methodologies for microbial community profiling and
      were unrelated to known lineages.

PMID- 24117984
TI  - The importance of language in the home for school-age children with permanent
      hearing loss.
AB  - AIM: To determine the characteristics of the natural spoken language environment
      associated with better language skills at school age of children with permanent
      hearing loss (HL) screened in a newborn hearing screen programme. METHODS: A
      language processor recorded language environment including child vocalisations
      (CVs), conversational turns (CTs), adult word count (AWC), percentage of language
      and percentage of silence in 23 children with HL and 41 hearing controls.
      Relationships of language environment scores with Reynell language scores were
      analysed. RESULTS: Children with HL had significantly lower Reynell comprehension
      scores (15-25 points; p = 0.0001) and expressive scores (7-12 points; NS) than
      hearing children. In regression analyses for the children with HL, after
      adjusting for age of entry to early intervention and stay in a NICU, every
      increase in ten percentage points of language in the home was associated with 7.2
      points higher comprehension score (p = 0.027) and 9.99 points higher expressive
      score (p = 0.006). After adjusting for nonverbal intelligence, similar
      independent effects of the language environment on both comprehension (p = 0.027)
      and expressive scores (p = 0.006) were identified. CONCLUSION: A rich language
      environment in the home is associated with better language abilities, which are
      necessary for academic success for children with permanent HL at school age.

PMID- 24117983
TI  - Early steps of adventitious rooting: morphology, hormonal profiling and
      carbohydrate turnover in carnation stem cuttings.
AB  - The rooting of stem cuttings is a common vegetative propagation practice in many
      ornamental species. A detailed analysis of the morphological changes occurring in
      the basal region of cultivated carnation cuttings during the early stages of
      adventitious rooting was carried out and the physiological modifications induced
      by exogenous auxin application were studied. To this end, the endogenous
      concentrations of five major classes of plant hormones [auxin, cytokinin (CK),
      abscisic acid, salicylic acid (SA) and jasmonic acid] and the ethylene precursor
      1-aminocyclopropane-1-carboxylic acid were analyzed at the base of stem cuttings
      and at different stages of adventitious root formation. We found that the
      stimulus triggering the initiation of adventitious root formation occurred during
      the first hours after their excision from the donor plant, due to the breakdown
      of the vascular continuum that induces auxin accumulation near the wounding.
      Although this stimulus was independent of exogenously applied auxin, it was
      observed that the auxin treatment accelerated cell division in the cambium and
      increased the sucrolytic activities at the base of the stem, both of which
      contributed to the establishment of the new root primordia at the stem base.
      Further, several genes involved in auxin transport were upregulated in the stem
      base either with or without auxin application, while endogenous CK and SA
      concentrations were specially affected by exogenous auxin application. Taken
      together our results indicate significant crosstalk between auxin levels, stress
      hormone homeostasis and sugar availability in the base of the stem cuttings in
      carnation during the initial steps of adventitious rooting. 

PMID- 24117985
TI  - Candida albicans adherence and proliferation on the surface of denture base
      materials.
AB  - OBJECTIVE: This study aimed to evaluate the adhesion and proliferation of Candida
      albicans on denture base materials with different resin chemistries. MATERIALS
      AND METHODS: Standardised specimens were prepared from different denture base
      materials (i.e. Palapress vario, Paladon 65, Castdon, Sherapress, Eclipse and
      Mucopren) and subjected to thermal cycling to simulate an artificial ageing
      process. After the determination of surface roughness and surface free energy,
      Candida albicans adherence and proliferation on the surface of denture base
      materials were simulated by subsequent incubation with Candida albicans ATCC
      10231 for either 24 h or 196 h with and without prior simulation of salivary
      pellicle formation. RESULTS: Regardless of the presence of a salivary pellicle or
      the incubation time, the results indicate that the proliferation of Candida
      albicans is significantly dependent on the material that is used for the
      fabrication of denture bases (p < 0.001). A significantly higher proliferation of
      Candida albicans was observed on the surface of denture base materials with the
      highest polar contribution to surface free energy (i.e. Eclipse, Mucopren), and
      this result supports the assumption that there might be a relationship between
      the polar contribution to surface free energy of the substratum material and
      Candida albicans proliferation. CONCLUSION: The results obtained from this study
      indicate that Candida albicans proliferation in particular is not necessarily
      increased on denture base materials that are subjected to thermal cycling.

PMID- 24117986
TI  - The contribution of preterm birth and intrauterine growth restriction to infant
      mortality in Tanzania.
AB  - BACKGROUND: Our objectives were to examine the associations of neonatal and
      infant mortality with preterm birth and intrauterine growth restriction (IUGR),
      and to estimate the partial population attributable risk per cent (pPAR%) of
      neonatal and infant mortality due to preterm birth and IUGR. METHODS:
      Participants were HIV-negative pregnant women and their infants enrolled in Dar
      es Salaam, Tanzania. Gestational age calculated from date of last menstrual
      period was used to define preterm, and small for gestational age (SGA) was used
      as proxy for IUGR. Survival of infants was ascertained at monthly follow-up
      visits. Cox proportional hazard models were used to estimate the associations of
      preterm and SGA with neonatal and infant mortality. RESULTS: Study included 7225
      singletons, of whom 15% were preterm and 21% were SGA; majority of preterm or SGA
      babies had birthweight >=2500 g. Compared to term and appropriately sized babies
      (AGA), relative risks (RR) of neonatal mortality among preterm-AGA was 2.6 [95%
      CI 1.8, 3.9], RR among term-SGA was 2.3 [95% CI 1.6, 3.3], and the highest risk
      was among the preterm-SGA babies (RR 15.1 [95% CI 8.2, 27.7]). Risk associated
      with preterm was elevated throughout the infancy, and risk associated with SGA
      was elevated during the neonatal period only. The pPAR% of neonatal mortality for
      preterm was 22% [95% CI 17%, 26%] and for SGA it was 26% [95% CI 16%, 36%].
      CONCLUSIONS: Preterm and SGA birth substantially increased the risk of mortality.
      Interventions for prevention and management of these conditions are likely to
      reduce of infant mortality in Tanzania.

PMID- 24117987
TI  - Transcriptional and post-translational regulation of Bim controls apoptosis in
      melatonin-treated human renal cancer Caki cells.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) has recently gained attention as an
      anticancer agent and for combined cancer therapy. In this study, we investigated
      the underlying molecular mechanisms of the effects of melatonin on cancer cell
      death. Treatment with melatonin induced apoptosis and upregulated the expression
      of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim) in
      renal cancer Caki cells. Furthermore, downregulation of Bim expression by siRNA
      markedly reduced melatonin-mediated apoptosis. Melatonin increased Bim mRNA
      expression through the induction of Sp1 and E2F1 expression and transcriptional
      activity. We found that melatonin also modulated Bim protein stability through
      the inhibition of proteasome activity. However, melatonin-induced Bim
      upregulation was independent of melatonin's antioxidant properties and the
      melatonin receptor. Taken together, our results suggest that melatonin induces
      apoptosis through the upregulation of Bim expression at the transcriptional level
      and at the post-translational level. 

PMID- 24117988
TI  - Reproduction of continuous flow left ventricular assist device experimental data
      by means of a hybrid cardiovascular model with baroreflex control.
AB  - Long-term mechanical circulatory assistance opened new problems in ventricular
      assist device-patient interaction, especially in relation to autonomic controls.
      Modeling studies, based on adequate models, could be a feasible approach of
      investigation. The aim of this work is the exploitation of a hybrid
      (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo
      experimental data acquired during a continuous flow left ventricular assistance.
      The hybrid cardiovascular simulator embeds three submodels: a computational
      cardiovascular submodel, a computational baroreflex submodel, and a
      hydronumerical interface submodel. The last one comprises two impedance
      transformers playing the role of physical interfaces able to provide a hydraulic
      connection with specific cardiovascular sites (in this article, the left atrium
      and the ascending/descending aorta). The impedance transformers are used to
      connect a continuous flow pump for partial left ventricular support (Synergy
      Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular
      simulator. Data collected from five animals in physiological, pathological, and
      assisted conditions were reproduced using the hybrid cardiovascular simulator.
      All parameters useful to characterize and tune the hybrid cardiovascular
      simulator to a specific hemodynamic condition were extracted from experimental
      data. Results show that the simulator is able to reproduce animal-specific
      hemodynamic status both in physiological and pathological conditions, to
      reproduce cardiovascular left ventricular assist device (LVAD) interaction and
      the progressive unloading of the left ventricle for different pump speeds, and to
      investigate the effects of the LVAD on baroreflex activity. Results in chronic
      heart failure conditions show that an increment of LVAD speed from 20 000 to 22
      000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3
      L/min). Thanks to its flexibility and modular structure, the simulator is a
      platform potentially useful to test different assist devices, thus providing
      clinicians additional information about LVAD therapy strategy. 

PMID- 24117989
TI  - Microscopic characterization of defect structure in RDX crystals.
AB  - Three batches of the commercial energetic material RDX, as received from various
      production locations and differing in sensitivity towards shock initiation, have
      been characterized with different microscopic techniques in order to visualize
      the defect content in these crystals. The RDX crystals are embedded in an epoxy
      matrix and cross-sectioned. By a treatment of grinding and polishing of the
      crystals, the internal defect structure of a multitude of energetic crystals can
      be visualized using optical microscopy, scanning electron microscopy and confocal
      scanning laser microscopy. Earlier optical micrographs of the same crystals
      immersed in a refractive index matched liquid could visualize internal defects,
      only not in the required detail. The combination of different microscopic
      techniques allows for a better characterization of the internal defects, down to
      inclusions of approximately 0.5 MUm in size. The defect structure can be
      correlated to the sensitivity towards a high-amplitude shock wave of the RDX
      crystals embedded in a polymer bonded explosive. The obtained experimental
      results comprise details on the size, type and quantity of the defects. These
      details should provide modellers with relevant and realistic information for
      modelling defects in energetic materials and their effect on the initiation and
      propagation of shock waves in PBX formulations.

PMID- 24117990
TI  - Maintaining shared knowledge of acquaintance: methods people use to establish who
      knows whom.
AB  - Acquaintance is a fundamental determinant of how people behave when interacting
      with one another. This article focuses on how this type of personal knowledge is
      an important consideration for people as social actors. Studying naturally
      occurring social encounters, I describe how speakers use particular references to
      convey whether a recipient should be able to recognize a non-present third party.
      On some occasions, however, the presumption of recognizability or non
      recognizability that underpins the use of a particular reference proves
      questionable. By exploring how recipients can challenge reference forms, and
      thereby reject claims of either recognizability or non-recognizability, I explain
      how people establish and maintain a shared understanding of who knows whom. I
      conclude by discussing motivations for this behaviour, and thereby contribute to
      understanding the commonsense reasoning that underpins orderly conduct in this
      aspect of social encounters. 

PMID- 24117991
TI  - Amplified Production of Singlet Oxygen in Aqueous Solution Using Metal
      Enhancement Effects.
AB  - Studies involving metal enhancement effects have gained popularity, and
      enhancement of fluorescence due to the close proximity of a dye molecule to a
      metal nanoparticle is well documented. Although enhancement of singlet oxygen
      production by metal has been reported, studies are relatively scarce and so far
      only stationary silver island films have been proven to be adequate to do so.
      Herein, we describe the synthesis and characterization of core-shell
      nanoparticles on which a photosensitizer acting as source of singlet oxygen has
      been covalently attached to the nanoparticle surface. As a proof of concept,
      silver nanoparticles with a diameter around 68 nm were chosen as the metallic
      core, and were coated by a silica shell of about 22 nm in thickness. The silica
      shell plays a dual role as a spacer and a medium onto which the photosensitizer,
      rose bengal (RB), has been covalently attached. These novel core-shell
      nanoparticles allow for the amplification of singlet oxygen production by 3.8
      times, which is similar to the amplification found for RB in proximity of silver
      island films.

PMID- 24117992
TI  - Rhizosphere stoichiometry: are C : N : P ratios of plants, soils, and enzymes
      conserved at the plant species-level?
AB  - As a consequence of the tight linkages among soils, plants and microbes
      inhabiting the rhizosphere, we hypothesized that soil nutrient and microbial
      stoichiometry would differ among plant species and be correlated within plant
      rhizospheres. We assessed plant tissue carbon (C) : nitrogen (N) : phosphorus (P)
      ratios for eight species representing four different plant functional groups in a
      semiarid grassland during near-peak biomass. Using intact plant species-specific
      rhizospheres, we examined soil C : N : P, microbial biomass C : N, and soil
      enzyme C : N : P nutrient acquisition activities. We found that few of the plant
      species' rhizospheres demonstrated distinct stoichiometric properties from other
      plant species and unvegetated soil. Plant tissue nutrient ratios and components
      of below-ground rhizosphere stoichiometry predominantly differed between the C4
      plant species Buchloe dactyloides and the legume Astragalus laxmannii. The
      rhizospheres under the C4 grass B. dactyloides exhibited relatively higher
      microbial C and lower soil N, indicative of distinct soil organic matter (SOM)
      decomposition and nutrient mineralization activities. Assessing the ecological
      stoichiometry among plant species' rhizospheres is a high-resolution tool useful
      for linking plant community composition to below-ground soil microbial and
      nutrient characteristics. By identifying how rhizospheres differ among plant
      species, we can better assess how plant-microbial interactions associated with
      ecosystem-level processes may be influenced by plant community shifts.

PMID- 24117993
TI  - Ultrasound measurement of reproductive organs in juvenile European sea bass
      Dicentrarchus labrax.
AB  - In this study, ultrasonographic examination was performed thrice, 15 days apart,
      on juvenile European sea bass Dicentrarchus labrax, from 330 to 360 days of age,
      to assess the size and the morphology of male and female. Results have proved
      this method as a suitable and non-invasive procedure to assess sexual
      differentiation. 

PMID- 24117994
TI  - Achieved pregnancy with the delivery of a healthy child by TESE-ICSI 7 years
      after bilateral adult orchidopexy: a case report.
AB  - We report pregnancy with the delivery of a healthy child by TESE-ICSI 7 years
      after bilateral adult orchidopexy. A 29-year-old patient presented with
      infertility and previous bilateral cryptorchidism, but no surgical treatment had
      ever been performed. His partner had been assessed by a gynaecologist, and no
      contributing female factors were detected. Orchidopexy and conventional
      testicular sperm extraction (TESE) were performed and microdissection TESE 10
      months after orchidopexy. The second microdissection TESE with intracytoplasmic
      sperm injection (ICSI) was performed 7 years after orchidopexy. The couple
      achieved pregnancy with the delivery of a healthy child by TESE-ICSI. It is
      concluded that bilateral orchidopexy in adulthood progresses spermatogenesis
      gradually, and microdissection TESE may succeed after a certain period of time
      following treatment.

PMID- 24117995
TI  - Prominent EMA 'dots' in tumour-induced Bergmann gliosis.
AB  - AIMS: To describe an unusual pattern of epithelial membrane antigen (EMA)
      immunoreactivity in highly proliferative human Bergmann glia. METHODS AND
      RESULTS: An immunohistochemical study was performed of postmortem cerebellar
      tissue from 18 adult patients with cerebellar damage of various aetiologies and
      15 biopsies of diverse adult and paediatric cerebellar tumours. We observed
      marked proliferation of Bergmann glia with unusual prominent dot-like cytoplasmic
      EMA immunoreactivity in a case with extensive leptomeningeal sarcomatosis.
      Similar staining was not observed in association with other types of cerebellar
      pathology, except for other neoplastic conditions, such as leptomeningeal
      carcinomatosis, adult medulloblastoma, and pilocytic astrocytoma in children. At
      an ultrastructural level, the index case showed prominent endoplasmic reticulum
      with some intermediate filaments and lipofuscin granules, but no structures
      related to cilia or microvilli were observed. CONCLUSIONS: We consider that
      prominent EMA dots in Bergmann glia might represent excessive activation induced
      by an overlying leptomeningeal tumour that stimulates the expression of early
      developmental antigens. This observation suggests modulation of the glial
      phenotype when exposed to a neoplastic microenvironment that, in turn, might
      influence the regenerative potential of Bergmann glia.

PMID- 24117996
TI  - Nicotine induces dendritic spine remodeling in cultured hippocampal neurons.
AB  - Cholinergic neurons in the CNS are involved in synaptic plasticity and cognition.
      Both muscarinic and nicotinic acetylcholine receptors (nAChRs) influence
      plasticity and cognitive function. The mechanism underlying nAChR-induced
      plasticity, however, has remained elusive. Here, we demonstrate morphological
      changes in dendritic spines following activation of alpha4beta2* nAChRs, which
      are expressed on glutamatergic pre-synaptic termini of cultured hippocampal
      neurons. Exposure of the neurons to nicotine resulted in a lateral enlargement of
      spine heads. This was abolished by dihydro-beta-erythroidine, an antagonist of
      alpha4beta2* nAChRs, but not by alpha-bungarotoxin, an antagonist of alpha7
      nAChRs. Tetanus toxin or a mixture of 2-amino-5-phosphonovaleric acid and 6-cyano
      7-nitroquinoxaline-2,3-dione, antagonists of NMDA- and AMPA-type glutamate
      receptors, blocked the nicotine-induced spine remodeling. In addition, nicotine
      exerted full spine-enlarging response in the post-synaptic neuron whose beta2
      nAChR expression was knocked down. Finally, pre-treatment with nicotine enhanced
      the Ca(2+)-response of the neurons to glutamate. These data suggest that nicotine
      influences the activity of glutamatergic neurotransmission through the activation
      of pre-synaptic alpha4beta2 nAChRs, resulting in the modulation of spinal
      architecture and responsiveness. The present findings may represent one of the
      cellular mechanisms underlying cholinergic tuning of brain function. Activation
      of nicotinic acetylcholine receptors (nAChRs) in brain influences plasticity and
      cognition. Here, activation of alpha4beta2* nAChRs, which are expressed on
      glutamatergic presynaptic termini, results in the enlargement of dendritic spines
      through the modulation of the glutamatergic neurotransmission. The remodeled
      spinal architecture might be responsible for the change in responsiveness of
      neural circuitry, leading to cholinergic tuning of brain function.

PMID- 24117997
TI  - A fluorescence-based method coupled with Disruptor filtration for rapid detection
      of F + RNA phages.
AB  - F + RNA phages are commonly used as indicators of faecal contamination. This
      study evaluated a fluorescent method for the detection of F + RNA phages based on
      testing the phage-mediated release of beta-galactosidase. Factors that may
      potentially interfere with phage detection were investigated, and the assay was
      optimized. Low numbers of F + RNA phages were detected by the fluorescent method
      coupled with a concentration step using a Disruptor filter. The fluorescent
      method, when used alone, detected 1 log PFU ml(-1) of F+RNA phages within 3 h,
      while 0.01 PFU ml(-1) was detected within 5 h when the method was combined with
      the concentration step. This is the first time to combine a fluorescent method
      with a filtration step by the use of Disruptor filter for rapid detection of low
      numbers of F + RNA phages, and this method can be adapted to detect other lytic
      phages infecting host cells that produce measurable enzyme activity. SIGNIFICANCE
      AND IMPACT OF THE STUDY: A fluorescent method coupled with Disruptor filtration
      was evaluated for the first time to rapidly detect low numbers of F + RNA phages.
      Rapid detection of F + RNA phages provides an effective way to monitor faecal
      contamination of environmental water and thus helps prevent contamination of
      fresh produce via irrigation.

PMID- 24117998
TI  - Pituitary apoplexy after somatostatin analogue administration: coincidental or
      causative?

PMID- 24117999
TI  - Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea:
      definition, classification, diagnosis.
AB  - Diarrhea is best defined as passage of loose stools often with more frequent
      bowel movements. For clinical purposes, the Bristol Stool Form Scale works well
      to distinguish stool form and to identify loose stools. Laboratory testing of
      stool consistency has lagged behind. Acute diarrhea is likely to be due to
      infection and to be self-limited. As diarrhea becomes chronic, it is less likely
      to be due to infection; duration of 1 month seems to work well as a cut-off for
      chronic diarrhea, but detailed scientific knowledge is missing about the utility
      of this definition. In addition to duration of diarrhea, classifications by
      presenting scenario, by pathophysiology, and by stool characteristics (e.g.
      watery, fatty, or inflammatory) may help the canny clinician refine the
      differential diagnosis of chronic diarrhea. In this regard, a careful history
      remains the essential part of the evaluation of a patient with diarrhea. Imaging
      the intestine with endoscopy and radiographic techniques is useful, and biopsy of
      the small intestine and colon for histological assessment provides key diagnostic
      information. Endomicroscopy and molecular pathology are only now being explored
      for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is
      increasing; aside from a handful of well-described infections because of
      pathogens, little is known about alterations in the microbiome in chronic
      diarrhea. Serological tests have well-defined roles in the diagnosis of celiac
      disease but have less clearly defined application in autoimmune enteropathies and
      inflammatory bowel disease. Measurement of peptide hormones is of value in the
      diagnosis and management of endocrine tumors causing diarrhea, but these are so
      rare that these tests are of little value in screening because there will be many
      more false-positives than true-positive results. Chemical analysis of stools is
      of use in classifying chronic diarrhea and may limit the differential diagnosis
      that must be considered, but interpretation of the results is still evolving.
      Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial
      overgrowth, and intestinal transit are fraught with technical limitations that
      decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption
      have had limited utility beyond empirical trials of bile acid sequestrants. 

PMID- 24118000
TI  - Cell type-dependent effects of corticosteroid on periostin production by primary
      human tissue cells.
AB  - Overproduction of periostin, an IL-13-inducible matricellular protein, despite
      corticosteroid treatment is thought to be involved in the chronicity of allergic
      inflammation seen in corticosteroid-refractory tissue fibrosis. Therefore, we
      hypothesized that some tissue cells must produce periostin in a corticosteroid
      insensitive manner. Here, we show that IL-4 and IL-13 each induced comparable
      levels of periostin production by primary normal human fibroblasts and
      microvascular endothelial cells derived from lung and skin. Dexamethasone, a
      corticosteroid, completely inhibited IL-4/13-induced, but did not affect TGF-beta
      induced, periostin production by fibroblasts. In contrast, dexamethasone
      synergistically enhanced IL-4/13-induced periostin production by microvascular
      endothelial cells. TGF-beta did not induce periostin production by microvascular
      endothelial cells. Our novel findings suggest that IL-4/13-induced microvascular
      endothelium-derived and/or TGF-beta-induced fibroblast-derived periostin might
      play a pivotal role in corticosteroid-refractory tissue fibrosis, leading to
      chronic allergic inflammation in the lung and/or skin. 

PMID- 24118001
TI  - The provision of weight management advice: an investigation into occupational
      therapy practice.
AB  - BACKGROUND/AIM: Obesity affects more than half the Australian population and has
      become epidemic throughout the world. Little is known regarding occupational
      therapy interventions with clients who are overweight or obese. This study aimed
      to identify occupational therapy practice in relation to the provision of weight
      management. This was part of a larger study investigating health professional
      practice. METHODS: A cross-sectional study design using a self-administered,
      purpose-designed survey was employed to identify the current practices of
      occupational therapists working in a regional area of New South Wales, Australia.
      Participants were recruited via email or mail as publically available. RESULTS:
      Fifty-one occupational therapists anonymously completed the survey. Results
      revealed that 53% (n = 26) of respondents did not consider weight management to
      be within their scope of practice or their workplace role description. The most
      common intervention was the provision of physical activity advice (65.2%; n =
      30). Dietary advice was provided by 20.8% (n = 10), while 77% (n = 32) referred
      onto dietitian services. During entry-level occupational therapy education, only
      7.8% (n = 4) had received weight management advice education. Completion of
      postgraduate professional development training in this area was reported by 14%
      (n = 7) of respondents. CONCLUSION: This study provides insight into the current
      practices of Australian occupational therapists in relation to the provision of
      weight management advice. This research displays a need to acknowledge both a
      generic and a discipline-specific role for the provision of healthy lifestyle
      interventions. This may be achieved through better access to education during
      entry-level programmes and in the workplace.

PMID- 24118002
TI  - The differential diagnosis of CD8-positive ("type D") lymphomatoid papulosis.
AB  - BACKGROUND: Cutaneous CD8(+) CD30(+) lymphoproliferative lesions are difficult to
      classify and encompass entities that follow a benign course to overt lymphoma. In
      order to identify histopathologic criteria for lesions in this spectrum, a series
      of such cases was reviewed. METHODS: Twenty-eight biopsies from 27 patients with
      CD8(+) CD30(+) cutaneous lymphoid proliferations were evaluated. RESULTS:
      Seventeen cases were classified as lymphomatoid papulosis (LyP) 'type D', eight
      as cutaneous anaplastic large cell lymphoma (C-ALCL) and two as CD8(+) mycosis
      fungoides (MF) with CD30 expression. Features of LyP included spongiosis and/or
      parakeratosis (90%), epidermotropism by large lymphocytes (90%), with (80%) or
      without (10%) small lymphocytes; wedge-shaped infiltrate (70%) with perivascular
      (100%) and interstitial (80%) pattern; and relative uniformity of CD30(+) large
      atypical cells (90%). C-ALCL was characterized by ulceration (63%),
      epidermotropism restricted to small lymphocytes (100%), marked density (63%) and
      pleomorphism (62%) of CD30(+) large atypical cells, and at least focal extension
      of infiltrate to subcutaneous tissue (88%). CD8(+) CD30(+) MF had vacuolar
      interface change and a lichenoid pattern (100%). CONCLUSIONS: We concur with
      previous authors that distinction of CD8(+) LyP from lymphoma in its differential
      diagnosis is difficult based on histopathology alone. Nonetheless, we propose
      that certain histopathologic clues may be helpful in this differential diagnosis.

PMID- 24118003
TI  - Household wealth and neurocognitive development disparities among school-aged
      children in Nepal.
AB  - BACKGROUND: Wealth disparities in child developmental outcomes are well
      documented in developed countries. We sought to (1) describe the extent of wealth
      based neurocognitive development disparities and (2) examine potential mediating
      factors of disparities among a population-based cohort of children in rural
      Nepal. METHODS: We investigated household wealth-based differences in
      intellectual, executive and motor function of n = 1692 children aged between 7
      and 9 years in Nepal. Using linear mixed models, wealth-based differences were
      estimated before and after controlling for child and household demographic
      characteristics. We further examined wealth-based differences adjusted for three
      sets of mediators: child nutritional status, home environment, and schooling
      pattern. RESULTS: We observed a positive gradient in child neurocognitive
      performance by household wealth. After adjusting for child and household control
      factors, disparities between children in the highest and lowest wealth quintiles
      persisted in intellectual and motor function, but not executive function. No
      statistically significant wealth-based differentials in outcomes remained after
      accounting for nutritional status, home environment, and schooling patterns. The
      largest differences in neurocognitive development were associated with schooling
      pattern. CONCLUSIONS: Household wealth patterns child neurocognitive development
      in rural Nepal, likely through its influence on nutritional status, the home
      environment, and schooling. In the current context, improving early and regular
      schooling in this setting is critical to addressing wealth-based disparities in
      outcomes.

PMID- 24118004
TI  - Checking the cheek bite injury: fabrication of an interim cheek guard appliance.
AB  - Among the various sequelae associated with the treatment of oral carcinoma (both
      surgical and radiotherapy), the two conditions that can be of serious concern are
      reduced mouth opening and mucositis. The limited mouth opening can lead to
      entrapment of buccal mucosa in between teeth during the chewing cycle, which in
      turn can lead to further injury of the mucosa. A simple method has been described
      by the authors to prevent the cheek bite by fabrication of a cheek guard
      appliance. Favorable results were seen within a few days after insertion of the
      appliance. 

PMID- 24118005
TI  - Long-term outcome after surgical ameroid ring constrictor placement for treatment
      of single extrahepatic portosystemic shunts in dogs.
AB  - OBJECTIVE: To report long-term clinical outcome in dogs treated for single
      congenital extrahepatic portosystemic shunt (CEHPSS) with a ameroid ring
      constrictor (ARC) and to identify perioperative variables associated with
      outcome. STUDY DESIGN: Retrospective, multi-institutional study. ANIMALS: Dogs (n
      = 206) with CEHPSS. METHODS: Medical records of dogs with CEHPSS treated by ARC
      were reviewed for perioperative and short-term (<1 month) data. Long-term follow
      up information was obtained by telephone interview with referring veterinarians
      and/or owners. Kaplan-Meier analysis was used to estimate median survival time.
      Factors associated with short-term survival, outcome grade, and total survival
      time were identified. RESULTS: Fifteen dogs died <1 month after ARC placement.
      Follow-up data were obtained for 112 of 191 dogs that survived >1 month; median
      follow was 54 months (range, 1-175 months) and 103 (92%) dogs had no clinical
      signs. Estimated median survival time was 152 months. Variables significantly
      associated with short-term survival included being intact and a low total white
      blood cell (WBC) count. Variables significantly associated with a successful
      outcome included having surgery later in the study period and negative
      postoperative nuclear scintigraphy. In the long-term survival analyses, intact
      dogs and those with higher WBC counts and occlusion pressures and lower bile acid
      concentrations were more likely to survive. CONCLUSIONS: Dogs with CEHPSS treated
      by ARC generally have a good prognosis and prolonged postoperative survival.

PMID- 24118006
TI  - An assessment of the biotechnological use of hemoglobin modulation in cereals.
AB  - Non-symbiotic hemoglobin (nsHb) genes are ubiquitous in plants, but their
      biological functions have mostly been studied in model plant species rather than
      in crops. nsHb influences cell signaling and metabolism by modulating the levels
      of nitric oxide (NO). Class 1 nsHb is upregulated under hypoxia and is involved
      in various biotic and abiotic stress responses. Ectopic overexpression of nsHb in
      Arabidopsis thaliana accelerates development, whilst targeted overexpression in
      seeds can increase seed yield. Such observations suggest that manipulating nsHb
      could be a valid biotechnological target. We studied the effects of
      overexpression of class 1 nsHb in the monocotyledonous crop plant barley (Hordeum
      vulgare cv. Golden Promise). nsHb was shown to be involved in NO metabolism in
      barley, as ectopic overexpression reduced the amount of NO released during
      hypoxia. Further, as in Arabidopsis, nsHb overexpression compromised basal
      resistance toward pathogens in barley. However, unlike Arabidopsis, nsHb ectopic
      overexpression delayed growth and development in barley, and seed specific
      overexpression reduced seed yield. Thus, nsHb overexpression in barley does not
      seem to be an efficient strategy for increasing yield in cereal crops. These
      findings highlight the necessity for using actual crop plants rather than
      laboratory model plants when assessing the effects of biotechnological approaches
      to crop improvement. 

PMID- 24118007
TI  - Concurrent hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of
      the scalp, and pyoderma gangrenosum in a 16-year-old boy.
AB  - We report the case of a 16-year-old boy who presented to our clinic with
      concomitant hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of
      the scalp, and pyoderma gangrenosum. Recent reports describe the co-occurrence of
      pyoderma gangrenosum, acne, and hidradenitis suppurativa. This case further
      expands the spectrum of concomitant pyoderma gangrenosum and dissecting
      cellulitis of the scalp. 

PMID- 24118008
TI  - Engraftment and outcome after autologous stem cell transplantation in plerixafor
      mobilized non-Hodgkin's lymphoma patients.
AB  - BACKGROUND: Plerixafor is used in combination with granulocyte-colony-stimulating
      factor to enhance the mobilization of hematopoietic stem cells. Limited data are
      available in regard to effects of plerixafor on posttransplant outcomes in
      chemomobilized patients who appear to mobilize poorly. STUDY DESIGN AND METHODS:
      Eighty-nine chemomobilized patients with non-Hodgkin's lymphoma (NHL) were
      included in this retrospective study. Thirty-three patients had received
      plerixafor preemptively (plerixafor group) and 56 patients served as controls.
      Posttransplantation outcomes including infections, hematologic recovery, and
      relapse were recorded. RESULTS: The median fold increase of CD34+ cells after the
      first plerixafor dose was 4.1 in patients mobilized with chemotherapy plus
      filgrastim and 7.2 in those mobilized with chemotherapy plus pegfilgrastim (p =
      0.027). The median number of collected CD34+ cells was 3.5 * 10(6) CD34+ cells/kg
      in the plerixafor group and 4.2 * 10(6) CD34+ cells/kg in the control group (p =
      0.076). Early engraftment was comparable between the groups (10 days for
      neutrophils >0.5 * 10(9) /L and 14 days for platelets >20 * 10(9) /L,
      respectively). Also late engraftment within 12 months was comparable except
      higher hemoglobin level at 3 months in the control group (121 g/L vs. 112 g/L, p
      = 0.009). Progression-free survival at 1 year after autologous stem cell
      transplantation (ASCT) was 79% in the plerixafor group and 86% in the control
      group (p = 0.399). CONCLUSIONS: Long-term engraftment and outcome after ASCT seem
      to be comparable in NHL patients receiving plerixafor compared to chemomobilized
      patients. These observations support the use of plerixafor in patients who
      mobilize poorly.

PMID- 24118009
TI  - Liposarcomas: diagnostic pitfalls and new insights.
AB  - Liposarcomas represent the most common histotype among soft tissue sarcomas.
      However, liposarcomas in fact constitute a heterogeneous group of distinctive
      lesions that pose several diagnostic difficulties. The current World Health
      Organization classification of soft tissue and bone tumours recognizes four major
      liposarcoma subtypes: (i) atypical lipomatous tumour/well-differentiated
      liposarcoma; (ii) de-differentiated liposarcoma; (iii) myxoid liposarcoma; and
      (iv) pleomorphic liposarcoma. These four main subgroups are characterized by
      distinctive morphologies, unique genetic findings as well as distinct clinical
      behaviour. Accurate classification requires the integration of morphological,
      immunohistochemical and (in selected situations) genetic findings, and is
      essential for providing patients with the best available treatments. This review
      will focus upon the main diagnostic pitfalls encountered in the routine diagnosis
      of liposarcoma, underlining the diagnostic value of combining morphology with
      cytogenetics and molecular genetics. 

PMID- 24118010
TI  - Modelled hydraulic redistribution by sunflower (Helianthus annuus L.) matches
      observed data only after including night-time transpiration.
AB  - The movement of water from moist to dry soil layers through the root systems of
      plants, referred to as hydraulic redistribution (HR), occurs throughout the world
      and is thought to influence carbon and water budgets and ecosystem functioning.
      The realized hydrologic, biogeochemical and ecological consequences of HR depend
      on the amount of redistributed water, whereas the ability to assess these impacts
      requires models that correctly capture HR magnitude and timing. Using several
      soil types and two ecotypes of sunflower (Helianthus annuus L.) in split-pot
      experiments, we examined how well the widely used HR modelling formulation
      developed by Ryel et al. matched experimental determination of HR across a range
      of water potential driving gradients. H. annuus carries out extensive night-time
      transpiration, and although over the last decade it has become more widely
      recognized that night-time transpiration occurs in multiple species and many
      ecosystems, the original Ryel et al. formulation does not include the effect of
      night-time transpiration on HR. We developed and added a representation of night
      time transpiration into the formulation, and only then was the model able to
      capture the dynamics and magnitude of HR we observed as soils dried and night
      time stomatal behaviour changed, both influencing HR.

PMID- 24118011
TI  - Detection and quantification of native microbial populations on soil-grown rice
      roots by catalyzed reporter deposition-fluorescence in situ hybridization.
AB  - Catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) was
      applied to detect microbial cells on the rhizoplane of wetland rice (Oryza sativa
      L.). Fluorescent signals of high intensity and specificity allowed for a reliable
      quantification of selected microbial phyla. Absolute cell numbers of archaea and
      bacteria were observed to be highest at flowering stage of rice plant development
      (P < 0.05) showing values of 1.32 and 6.26 * 10(4)  cells mm(-2) rhizoplane,
      respectively. Highest colonization densities shifted from the root tip toward
      more mature regions with increasing plant age. Significant differences between
      cell numbers observed within a short distance (0-15 mm) indicated irregular
      distribution patterns of microbiota. Root tips, elongation zones, and openings at
      the base of lateral roots represented preferential areas for microbial
      colonization, which were often covered with iron coatings and densely colonized
      with potential iron-oxidizing Betaproteobacteria (59% of bacteria). Methanogenic
      archaea were abundant on the rhizoplane (up to 0.96 * 10(3)  cells mm(-2)
      rhizoplane), and the decline of their relative abundance with plant age was also
      found in the associated rhizosphere soil. Cell numbers of methanotrophic bacteria
      significantly increased at flowering (6.38 * 10(3)  cells mm(-2) rhizoplane; P <
      0.05), indicating their stimulation by root-derived substrates which was less
      pronounced in the rhizosphere soil. 

PMID- 24118012
TI  - Review of insulin treatment in stress-related hyperglycaemia in children without
      preexisting diabetes.
AB  - A systematic review was undertaken to assess the effect of using insulin therapy
      in the treatment for stress hyperglycaemia in children without preexisting
      diabetes in: achieving normoglycaemia, improving symptoms associated with
      hyperglycaemia and survival, and to determine if any adverse effects were
      associated with the use of insulin therapy. CONCLUSION: There is currently
      insufficient evidence for the routine use of insulin therapy in stress
      hyperglycaemia compared with conventional care in children without preexisting
      diabetes.

PMID- 24118013
TI  - Personality, emotional adjustment, and cardiovascular risk: marriage as a
      mechanism.
AB  - A variety of aspects of personality and emotional adjustment predict the
      development and course of coronary heart disease (CHD), as do indications of
      marital quality (e.g., satisfaction, conflict, strain, disruption). Importantly,
      the personality traits and aspects of emotional adjustment that predict CHD are
      also related to marital quality. In such instances of correlated risk factors,
      traditional epidemiological and clinical research typically either ignores the
      potentially overlapping effects or examines independent associations through
      statistical controls, approaches that can misrepresent the key components and
      mechanisms of psychosocial effects on CHD. The interpersonal perspective in
      personality and clinical psychology provides an alternative and integrative
      approach, through its structural and process models of interpersonal behavior. We
      present this perspective on psychosocial risk and review research on its
      application to the integration of personality, emotional adjustment, and marital
      processes as closely interrelated influences on health and disease. 

PMID- 24118015
TI  - Cannabidiol reverses the mCPP-induced increase in marble-burying behavior.
AB  - Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical
      and preclinical anxiolytic properties. Recent results using the marble-burying
      test (MBT) suggest that CBD can also induce anticompulsive-like effects. Meta
      chloro-phenyl-piperazine (mCPP) is a nonspecific serotonergic agonist (acting
      mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD
      patients and block the anticompulsive-like effect of serotonin reuptake
      inhibitors (SRIs) in animal models. The aim of this study was to investigate the
      interference of CBD on mCPP effects in repetitive burying. Administration of mCPP
      showed dual effects in the MBT, increasing the number of buried marbles at lower
      (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related
      to a general increase in anxiety-like behavior. As found previously, CBD (30
      mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying
      behavior without changing general exploratory activity. A similar effect was
      found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were
      administered together. These subeffective doses alone were also able to block
      mCPP-induced repetitive burying. The results, in addition to reinforcing a
      possible anticompulsive effect of CBD, also suggest that mCPP-induced repetitive
      burying could be a useful test for the screening of compounds with presumed
      anticompulsive properties.

PMID- 24118014
TI  - Pharmacological strategies for detoxification.
AB  - Detoxification refers to the safe discontinuation from a substance of dependence
      and is distinct from relapse prevention. Detoxification usually takes between a
      few days and a few weeks to complete, depending on the substance being misused,
      the severity of dependence and the support available to the user. Psychosocial
      therapies alongside pharmacological treatments are essential to improve outcome.
      The dependencies considered in this overview are detoxification from opioids
      (with methadone, buprenorphine, alpha2-adrenoceptor agonists and adjunct
      medications), alcohol (with benzodiazepines, anti-glutamatergics and gamma
      aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear
      recommended pharmacological treatments), benzodiazepines (with dose tapering) and
      nicotine (with nicotine replacement therapy, antidepressants and partial
      agonists). Evidence is limited by a lack of controlled trials robust enough for
      review bodies, and more research is required into optimal treatment doses and
      regimes, alone and in combination.

PMID- 24118016
TI  - Pharmacokinetics and residue depletion of erythromycin in rainbow trout
      Oncorhynchus mykiss (Walbaum).
AB  - Erythromycin (ERY) is a drug active against Gram-positive bacteria such as
      Lactococcus garvieae, a pathogen responsible for an important disease that may
      cause a substantial decrease in rainbow trout Oncorhynchus mykiss (Walbaum)
      production, the species of fish most commonly produced in Italy. In the
      literature, studies on the kinetics behaviour of ERY in fish are limited.
      Therefore, the aim of the present study was to evaluate the pharmacokinetics of
      ERY in rainbow trout after a single oral treatment with 75 mg kg-1 body weight
      (b.w.) of ERY and the residue depletion after multiple oral administration of 75
      mg kg-1 b.w. day-1 of ERY for 10 days. Blood concentrations of ERY increased up
      to 20.24 +/- 13.32 MUg mL-1 at 6 h, then decreased to 5.97 +/- 3.89 MUg mL-1 at
      24 h. The time during which the antibiotic remains in the bloodstream at
      concentrations exceeding the MIC (T > MIC) and the area under the serum
      concentration-time curve (AUC)/MIC are both pharmacokinetic-pharmacodynamic
      (PK/PD) predictors of ERY efficacy, and the data obtained allowed us to
      hypothesize that a dosage of 75 mg kg-1 b.w. day-1 of ERY could treat the
      lactococcosis in trout. Regarding the study of ERY depletion, rapid elimination
      was observed in tissue (muscle plus adherent skin); in fact the concentrations
      were below the limit of quantification in all samples (except two) by day 10 post
      treatment. ERY is not licensed in Europe for use in aquaculture, and its use is
      possible only by off-label prescription with a precautionary withdrawal time of
      500 degree-days, as established by Directive 2004/28/EC. From the data obtained
      in this study, a withdrawal time of 8.90 days was calculated, corresponding, in
      our experimental conditions, to 117.5 degree-days, a value significantly lower
      than that established by the European directive.

PMID- 24118017
TI  - Automated image segmentation of haematoxylin and eosin stained skeletal muscle
      cross-sections.
AB  - The ability to accurately and efficiently quantify muscle morphology is essential
      to determine the physiological relevance of a variety of muscle conditions
      including growth, atrophy and repair. There is agreement across the muscle
      biology community that important morphological characteristics of muscle fibres,
      such as cross-sectional area, are critical factors that determine the health and
      function (e.g. quality) of the muscle. However, at this time, quantification of
      muscle characteristics, especially from haematoxylin and eosin stained slides, is
      still a manual or semi-automatic process. This procedure is labour-intensive and
      time-consuming. In this paper, we have developed and validated an automatic image
      segmentation algorithm that is not only efficient but also accurate. Our proposed
      automatic segmentation algorithm for haematoxylin and eosin stained skeletal
      muscle cross-sections consists of two major steps: (1) A learning-based seed
      detection method to find the geometric centres of the muscle fibres, and (2) a
      colour gradient repulsive balloon snake deformable model that adopts colour
      gradient in Luv colour space. Automatic quantification of muscle fibre cross
      sectional areas using the proposed method is accurate and efficient, providing a
      powerful automatic quantification tool that can increase sensitivity, objectivity
      and efficiency in measuring the morphometric features of the haematoxylin and
      eosin stained muscle cross-sections. 

PMID- 24118018
TI  - Coordination chemistry-assembled multicomponent systems built from a gable-like
      bis-porphyrin: synthesis and photophysical properties.
AB  - Multiporphyrinic assemblies were quantitatively formed, in one step, from a gable
      like zinc(II) bis-porphyrin ZnP2 and free-base porphyrins bearing pyridyl groups.
      The different fragments are held together by axial 4'-N(pyridyl)-Zn interactions.
      Formation of a macrocycle ZnP2 *(4'-cisDPyP) and a bis-macrocycle (ZnP2 )2
      *(TPyP) is discussed. The macrocycle and the bis-macrocycle were crystallized and
      studied by X-ray diffraction, which confirmed the excellent complementarity
      between the various components. Spectrophotometric and spectrofluorimetric
      titrations and studies reveal high association constants for both
      multiporphyrinic assemblies due to the almost perfect geometrical match between
      the interacting units. As expected, energy transfer from the zinc porphyrin
      component to the free-base porphyrin quenches the fluorescence of the zinc
      porphyrin components in both compounds. But while in ZnP2 *(4'-cis DPyP)
      sensitization of the emission of the free-base porphyrin was observed, in (ZnP2)2
      *(TPyP) excitation of the peripheral Zn porphyrin units does not lead to
      quantitative sensitization of the luminescence of the free-base porphyrin
      acceptor. An unusual HOMO-HOMO electron transfer reaction from ZnP2 to the
      excited TPyP unit was detected and studied.

PMID- 24118019
TI  - Abeta40 modulates GABA(A) receptor alpha6 subunit expression and rat cerebellar
      granule neuron maturation through the ERK/mTOR pathway.
AB  - In addition to their neurotoxic role in Alzheimer's disease (AD), beta-amyloid
      peptides (Abetas) are also known to play physiological roles. Here, we show that
      recombinant Abeta40 significantly increased the outward current of the GABA(A)
      receptor containing (GABA(A)alpha6) in rat cerebellar granule neurons (CGNs). The
      Abeta40-mediated increase in GABA(A)alpha6 current was mediated by an increase in
      GABA(A)alpha6 protein expression at the translational rather than the
      transcriptional level. The exposure of CGNs to Abeta40 markedly induced the
      phosphorylation of ERK (pERK) and mammalian target of rapamycin (pmTOR). The
      increase in GABA(A)alpha6 current and expression was attenuated by specific
      inhibitors of ERK or mTOR, suggesting that the ERK and mTOR signaling pathways
      are required for the effect of Abeta40 on GABA(A)alpha6 current and expression in
      CGNs. A pharmacological blockade of the p75 neurotrophin receptor (p75(NTR)), but
      not the insulin or alpha7-nAChR receptors, abrogated the effect of Abeta40 on
      GABA(A)alpha6 protein expression and current. Furthermore, the expression of
      GABA(A)alpha6 was lower in CGNs from APP(-/-) mice than in CGNs from wild-type
      mice. Moreover, the internal granule layer (IGL) in APP(-/-) mice was thinner
      than the IGL in wild-type mice. The injection of Abeta40 into the cerebellum
      reversed this effect, and the application of p75(NTR) blocking antibody abolished
      the effects of Abeta40 on cerebellum morphology in APP(-/-) mice. Our results
      suggest that low concentrations of Abeta40 play a role in regulating CGN
      maturation through p75(NTR).

PMID- 24118020
TI  - Antibacterial and antiviral evaluation of sulfonoquinovosyldiacylglyceride: a
      glycolipid isolated from Azadirachta indica leaves.
AB  - Assessment of antibacterial as well as antiherpes virus activity of
      sulfonoquinovosyldiacylglyceride (SQDG), a glycolipid, isolated from the leaves
      of Azadirachta indica has been described. Antimicrobial activity was evaluated
      against Gram-positive, Gram-negative bacteria and herpes simplex virus. SQDG
      showed significant inhibitory activity against Salmonella typhi and two isolates
      of Shigella dysenteriae with MIC values 32 MUg ml(-1) , while three isolates of
      Salm. typhi, Escherichia coli and Vibrio cholerae were inhibited at 64 MUg ml(-1)
      and have shown zone diameter ranging from 6.2 to 12.3 mm. The growth kinetics
      study of SQDG on Salm. typhi and Sh. dysenteriae revealed that the growths were
      completely inhibited at their MIC values within 24 h of exposure. Interestingly,
      SQDG inhibits herpes simplex virus (HSV) type 1 and 2 with the EC50 of 9.1 and
      8.5 MUg ml(-1) , compared with acyclovir (2.2 and 2.8 MUg ml(-1) against HSV-1
      and HSV-2). The selectivity index (SI) was found to be 12.4 against HSV-1 and
      13.41 with HSV-2. Furthermore, the expression of proinflammatory cytokines of HSV
      infected and SQDG-treated macrophages using ELISA kit revealed that SQDG
      significantly downregulated the production of TNF-alpha, IL-1beta, IL-12 and IL
      6. SIGNIFICANCE AND IMPACT OF THE STUDY: The water-soluble metabolite
      sulfonoquinovosyldiacylglyceride (SQDG) isolated from Azadirachta indica (Neem)
      possess significant antibacterial as well as anti-HSV activity. The efficacies as
      well as the solubility factor of SQDG substantiate a greater attention for its
      use as phytotherapeutic drug for controlling microbial infections as most
      consumers have better acceptance of phytomedicines than synthetic drugs.

PMID- 24118021
TI  - Adaptations of anaerobic archaea to life under extreme energy limitation.
AB  - Some anaerobic archaea live on substrates that do not allow the synthesis of 1
      mol of ATP per mol of substrate. Energy conservation in these cases is only
      possible by a chemiosmotic mechanism that involves the generation of an
      electrochemical ion gradient across the cytoplasmatic membrane that then drives
      ATP synthesis via an A1AO ATP synthase. The minimal amount of energy required is
      thus depending on the magnitude of the electrochemical ion gradient, the
      phosphorylation potential, and the ion/ATP ratio of the ATP synthase.
      Methanogens, Thermococcus, Pyrococcus, and Ignicoccus have evolved different ways
      to energize their membranes, such as methyltransferases, H+, or NAD+ reducing
      electron transport systems fueled by reduced ferredoxin or H2 -dependent sulfur
      reduction that all operate at the thermodynamic limit of life. The structure and
      function of the enzymes involved are discussed. Despite the differences in
      membrane energization, they have in common an A1AO ATP synthase that shows an
      extraordinary divergence in rotor composition and structural adaptations to life
      under these conditions. In sum, adaptation of anaerobic archaea to energy-limited
      substrates involves chemiosmotic energy coupling, often with Na+ as coupling ion
      and a structurally and functionally highly adapted ATP synthase.

PMID- 24118022
TI  - Total submission of pelvic lymphadenectomy tissues removed during radical
      prostatectomy for prostate cancer increases lymph node yield and detection of
      micrometastases.
AB  - AIMS: The detection of lymph node metastases has prognostic and therapeutic
      implications for patients undergoing radical prostatectomy for prostate cancer.
      Macroscopic identification of pelvic lymph nodes in surgical lymphadenectomy
      specimens can be difficult, with a potential for incomplete submission of lymph
      nodes for microscopic examination. This study was undertaken to determine whether
      complete sampling of lymphadenectomy specimens would improve the detection of
      metastatic disease in patients undergoing radical prostatectomy. METHODS AND
      RESULTS: We examined 109 pelvic lymphadenectomies accompanying radical
      prostatectomy specimens to assess the benefit of complete submission of the lymph
      node packets to detect extra lymph nodes and metastatic disease. We found that
      blocking the residual tissue, after all palpable lymph nodes had been identified,
      increased the mean number of lymph nodes from 3.8 to 10.8, with an average of
      0.84 macroscopically undetectable nodes being recovered per block submitted.
      Metastatic prostate cancer was identified in eight cases, one of which had cancer
      in an impalpable lymph node only. CONCLUSIONS: Submission of all pelvic
      lymphadenectomy tissue for histological examination improves the yield of lymph
      nodes and the detection of metastatic prostate cancer.

PMID- 24118023
TI  - Relevance of serum nitric oxide levels and the efficacy of selective serotonin
      reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is
      associated with premature ejaculation.
AB  - The aim of the present study was to determine the relevance of serum nitric oxide
      levels and the efficacy of selective serotonin reuptake inhibitors (SSRI)
      treatment on premature ejaculation. Sixty married men (aged 20-50) with lifelong
      premature ejaculation and forty healthy men (aged 24-48) as control group were
      included in this study. The patients were evaluated by intravaginal ejaculation
      latency time (IELT) for premature ejaculation (PE). IELT<1 min is accepted PE.
      Patients with diabetes mellitus, chronic disorders or erectile dysfunction and
      heavy smokers were excluded. All patients were evaluated with history, physical
      examination, International Index of Erectile Dysfunction-5 (IIEF-5) score and
      IELT by stopwatch method. Nitric oxide levels were measured by Griess reaction,
      and all samples were frozen at -80  degrees C. Patients were randomly categorised
      4 group to receive fluoxetine 20 mg day(-1) (Group 1), paroxetine 20 mg day(-1)
      (Group 2), sertraline 50 mg day(-1) (Group 3) and healthy control (Group 4) for 4
      weeks. Baseline and post-treatment findings were compared between the four
      groups. At the end of 4 weeks, in fluoxetine, paroxetine, sertraline groups mean
      IELT values showed a statistically significant improvement from the baseline
      values (P < 0.001, P < 0.001, P = 0.03; respectively). Baseline and 1st month
      follow-up mean IIEF scores were 24.5 and 23.05, 24.70 and 23.60 (P < 0.05) in
      group 1 and group 3 respectively; also 23.09 and 23.32 (P > 0.05) in group 2.
      Baseline serum NO levels were 31.8, 30.44, 30.8 and 42.84 in fluoxetine,
      paroxetine, sertraline and healthy control groups respectively. NO levels were
      statistically lower in patients with PE. After treatment of fluoxetine,
      paroxetine and sertraline, NO levels were increased baseline (35.8, 36.4, 38.08)
      (P < 0.05). Our findings indicated that PE is associated with decreased serum NO
      levels. After the SSRI treatment increased, NO may retard ejaculation presumably
      by central peripheral mechanism. Further studies are needed to confirm this
      suggestion and the role of NO in pathophysiology and treatment for premature
      ejaculation. 

PMID- 24118024
TI  - Short-term in vivo performance of the Cleveland clinic PediPump left ventricular
      assist device.
AB  - The PediPump was implanted in six healthy lambs (mean 25.6 +/- 1.4 kg) between
      the left ventricular apex and the descending aorta to evaluate in vivo
      performance for up to 30 days. Anticoagulation was achieved by continuous heparin
      infusion. Three animals were euthanized prematurely, two because of respiratory
      dysfunction and one because of deteriorating pump performance resulting from
      thrombus formation inside the pump. Three lambs were electively sacrificed 30
      days after implantation; all had stable hemodynamics and minimal hemolysis, as
      indicated by low plasma free hemoglobin (2.5 +/- 3.1 mg/dL). Mean 30-day pump
      flow was 1.8 +/- 0.1 L/min at a pump speed of 12 200 +/- 400 rpm. Neither
      activated clotting time nor activated partial thromboplastin time followed the
      changes in heparin dose. At necropsy, depositions were observed at the front (n =
      1) and rear rotor axial positioning stops (n = 4); improved polishing techniques
      on the stationary stop surfaces and the addition of a hard-carbon, thin-film
      coating on the rotating stop of the pumps used for the last two experiments
      addressed the deposition seen earlier. In conclusion, the PediPump showed
      excellent hydraulic performance and minimal hemolysis during support for up to 30
      days. Depositions observed at the axial positioning stops in earlier experiments
      were addressed by design and material refinements. We continue to focus on
      developing effective anticoagulation management in the lamb model as well as on
      further evaluating and demonstrating pump biocompatibility. 

PMID- 24118025
TI  - Probability and predictors of patients converting from negative to positive
      screens for alcohol misuse.
AB  - BACKGROUND: Medicare reimburses providers for annual alcohol screening. However,
      the benefit of rescreening patients a year after a negative screen for alcohol
      misuse is unknown. We hypothesized that some subgroups of patients who screen
      negative would have a very low probability of converting to a positive subsequent
      screen (e.g., <0.1%), calling into question the value of annual alcohol screening
      for some patient subgroups. METHODS: This retrospective cohort study estimated
      the probability of converting to a positive screen for alcohol misuse a year
      after a negative screen among outpatients from 30 Veterans Health Administration
      (VA) medical centers. Alcohol Use Disorders Identification Test-Consumption
      (AUDIT-C) alcohol screening scores (range 0 to 12 points) from 2004 to 2008 were
      obtained from electronic health record data. Eligible patients screened negative
      on their initial screen (AUDIT-C scores 0 to 3 for men; 0 to 2 for women). The
      main outcome was a positive subsequent screen (AUDIT-C scores >=4 men; >=3
      women). RESULTS: Among 21,081 women and 323,913 men who screened negative on an
      initial screen, 5.4% and 6.0%, respectively, screened positive a year later. The
      adjusted probability of converting to a positive subsequent screen varied from
      2.1 to 38.9% depending on age, gender, and initial negative screen score. Women,
      older patients, and those with initial AUDIT-C scores of 0 were least likely to a
      convert to a positive subsequent screen, while younger men with AUDIT-C scores of
      3 were most likely to a convert to a positive subsequent screen. CONCLUSIONS: The
      probability of a positive subsequent screen varied depending on age, gender, and
      initial negative screen score but exceeded 2% in all patient subgroups. Annual
      rescreening appears reasonable for all VA patients who had a negative screen the
      year prior.

PMID- 24118026
TI  - Predicting risk of spontaneous preterm delivery in women with a singleton
      pregnancy.
AB  - BACKGROUND: Prediction of a woman's risk of a spontaneous preterm delivery (PTD)
      is a core challenge and an unresolved problem in today's obstetric practice. The
      objective of this study was to develop prediction models for spontaneous PTD (<37
      weeks). METHODS: A population-based register study of women born in Sweden with
      spontaneous onset of delivery was designed using Swedish Medical Birth Register
      data for 1992-2008. Predictive variables were identified by multiple logistic
      regression analysis, and outputs were used to calculate adjusted likelihood
      ratios in primiparous (n = 199 272) and multiparous (n = 249 580) singleton
      pregnant women. The predictive ability of each model was validated in a separate
      test sample for primiparous (n = 190 936) and multiparous (n = 239 203) women,
      respectively. RESULTS: For multiparous women, the area under the ROC curve (AUC)
      of 0.74 [95% confidence interval (CI) 0.73, 0.74] indicated a satisfying
      performance of the model, while for primiparous women, it was rather poor {AUC:
      0.58 [95% CI 0.57, 0.58]}. For both primiparous and multiparous women, the
      prediction models were quite good for pregnancies with comparatively low risk for
      spontaneous PTD, whereas more limited to predict pregnancies with >=30% risk of
      spontaneous PTD. CONCLUSIONS: Spontaneous PTD is difficult to predict in
      multiparous women and nearly impossible in primiparous, by using this statistical
      method in a large and unselected sample. However, adding clinical data (like
      cervical length) may in the future further improve its predictive performance.

PMID- 24118027
TI  - Peripheral blood stem cell yield calculated using preapheresis absolute CD34+
      cell count, peripheral blood volume processed, and donor body weight accurately
      predicts actual yield at multiple centers.
AB  - BACKGROUND: Accurate prediction of stem cell yield is important for planning
      leukapheresis procedures. A formula has been published (Pierelli et al., Vox Sang
      2006;91:126-34) to estimate the CD34+ dose collected on the first day of
      leukapheresis that was based on the preapheresis peripheral blood (PB) CD34+
      counts, the blood volume processed, and the donor's weight. The aim of this study
      was to assess the predictive value of this formula. STUDY DESIGN AND METHODS:
      Data were retrospectively collected on 1126 consecutive PB stem cell harvests
      conducted at five institutions. Information on age, sex, diagnosis, weight,
      preapheresis absolute peripheral CD34+ count, total blood volume processed, and
      CD34+ cells harvested per kilogram of body weight on the first day of apheresis
      was collected. RESULTS: Among donors at least 18 years old, Pearson's correlation
      coefficient (r) between actual yield (AY) and predicted yield (PY) was 0.76. To
      characterize this correlation, AY and PY were classified as being within the
      conventionally acceptable CD34+ doses (>2 * 10(6) -5 * 10(6) cells/kg), below
      this range (<=2 * 10(6) cells/kg), or above it (>5 * 10(6) cells/kg). The
      positive predictive value (PPV) of PY was estimated considering the distribution
      of AY as the "gold standard." PPV was relatively high for PY of more than 5 *
      10(6) cells/kg (85%), moderate for PY of not more than 2 * 10(6) cells/kg (72%),
      and low for PY more than 2 * 10(6) to 5 * 10(6) cells/kg (56%). A consistent
      pattern was observed within institutions. CONCLUSION: The formula of Pierelli et
      al. is associated with a PPV that is high, moderate, and relatively low for the
      corresponding predicted CD34+ doses.

PMID- 24118028
TI  - The impact of high dietary zinc oxide on the development of the intestinal
      microbiota in weaned piglets.
AB  - Weaned piglets were fed diets containing 57 (low) or 2425 (high) mg kg(-1)
      analytical grade ZnO for a period of 5 weeks. Intestinal contents were sampled in
      weekly intervals and analyzed for bacterial cell numbers and main bacterial
      metabolites. The most severe effects of high dietary zinc were observed 1 week
      after weaning in the stomach and small intestine. Pronounced reductions were
      observed for Enterobacteriaceae and the Escherichia group as well as for
      Lactobacillus spp. and for three of five studied Lactobacillus species. The
      impact of high dietary zinc diminished for enterobacteria with increasing age,
      but was permanent for Lactobacillus species. Bifidobacteria, enterococci,
      streptococci, Weissella spp. and Leuconostoc spp. as well as the Bacteroides
      Prevotella-Porphyromonas group were not influenced by high dietary zinc
      throughout the trial. High dietary zinc reduced bacterial metabolite
      concentrations and increased molar acetate ratios at the expense of propionate in
      the proximal intestine, but differences diminished in older animals. Lower
      lactate concentrations were observed in the high dietary zinc group throughout
      the feeding trial. This study has shown that the application of dietary zinc at
      high concentrations leads to transient and lasting effects during the development
      of the intestinal microbiota, affecting composition as well as metabolic
      activity. 

PMID- 24118029
TI  - Is there relationship between temporomandibular disorders and head and cervical
      posture? A systematic review.
AB  - The objective of this systematic review was to find sufficient evidence to deny
      or accept the association between the head and cervical posture and
      temporomandibular disorders (TMDs), and thus assist health professionals in the
      evaluation and treatment of patients with TMDs. A search was conducted through
      all publications written in English about this topic using the databases from
      Medline, ISI Web of Science, EMBASE, PubMed and Lilacs. The abstracts that
      fulfilled the initial guideline were retrieved and evaluated to ensure they met
      the inclusion criteria. To assess the methodological quality of the studies, we
      developed a questionnaire considering the following criteria: participant's
      eligibility, control group, diagnosis of TMDs, posture diagnosis and
      randomisation. Twenty-two studies were selected as potential studies based on
      their abstracts. Only seventeen studies actually fulfilled the inclusion
      criteria. The search provided information about the methodological quality of the
      studies, in which several methodological defects were found. The evidence
      presented in this systematic review shows that the relation between TMDs and the
      head and neck posture is still controversial and unclear. The insufficient number
      of articles considered of excellent methodological quality is a factor that
      hinders the acceptance or denial of this association. 

PMID- 24118030
TI  - Percutaneous and surgical insertion of peritoneal catheter in patients starting
      in chronic dialysis therapy: a comparative study.
AB  - Percutaneous peritoneal catheter insertion can be performed by trained
      nephrologists. The objective of this study was to compare the outcome of
      peritoneal dialysis (PD) catheters percutaneous inserted with the traditional
      surgical technique. One hundred twenty-one PD catheters were placed in 121 stage
      5 Chronic kidney disease patients using three techniques: percutaneous insertion
      (Group P, n = 53), percutaneous insertion guided by radioscopy (Group R, n = 26),
      and surgical insertion (Group S, n = 42). The mean age of the whole cohort was 57
      +/- 16 years and 54% were male. Patients and catheter outcomes were followed up
      prospectively for 19 months. Gender, age, body mass index, previous abdominal
      surgeries, and the prevalence of diabetes mellitus were not significantly
      different among the groups as well as the incidence of bleeding and the presence
      of catheter dysfunction. In addition, the incidence of exit-site infections and
      peritonitis was not significantly different among the groups. Finally, the
      survival catheter rate was not significantly different by the end of the follow
      up of 19 months (70% in P group, 85% in R, and 70% in S group (log rank = 0.88, p
      = 0.95). The outcome of percutaneous implanted catheters, which were inserted by
      a trained nephrologist, did not demonstrate to be inferior as compared with the
      traditional surgical approach.

PMID- 24118032
TI  - Bacteria isolated from roots and rhizosphere of Vitis vinifera retard water
      losses, induce abscisic acid accumulation and synthesis of defense-related
      terpenes in in vitro cultured grapevine.
AB  - Eleven bacterial strains were isolated at different soil depths from roots and
      rhizosphere of grapevines from a commercial vineyard. By 16S rRNA gene sequencing
      10 different genera and 8 possible at species level were identified. From them,
      Bacillus licheniformis Rt4M10 and Pseudomonas fluorescens Rt6M10 were selected
      according to their characteristics as plant growth promoting rhizobacteria
      (PGPR). Both produced abscisic acid (ABA), indole-3-acetic acid (IAA) and the
      gibberellins A1 and A3 in chemically-defined medium. They also colonized roots of
      in vitro grown Vitis vinifera cv. Malbec plants. As result of bacterization ABA
      levels in 45 days-old in vitro plants were increased 76-fold by B. licheniformis
      and 40-fold by P. fluorescens as compared to controls. Both bacteria diminished
      plant water loss rate in correlation with increments of ABA. Twenty and 30 days
      post bacterization the plants incremented terpenes. The monoterpenes alpha
      pinene, terpinolene, 4-carene, limonene, eucalyptol and lilac aldehyde A, and the
      sesquiterpenes alpha-bergamotene, alpha-farnesene, nerolidol and farnesol were
      assessed by gas chromatography-electron impact mass spectrometry analysis. alpha
      Pinene and nerolidol were the most abundant (ug per g of tissue in plants
      bacterized with P. fluorescens). Only alpha-pinene, eucalyptol and farnesol were
      identified at low concentration in non-bacterized plants treated with ABA, while
      no terpenes were detected in controls. The results obtained along with others
      from literature suggest that B. licheniformis and P. fluorescens act as stress
      alleviators by inducing ABA synthesis so diminishing water losses. These bacteria
      also elicit synthesis of compounds of plant defense via an ABA independent
      mechanism. 

PMID- 24118031
TI  - Wheeze in infancy: protection associated with yeasts in house dust contrasts with
      increased risk associated with yeasts in indoor air and other fungal taxa.
AB  - BACKGROUND: While fungal exposures are assumed to provoke wheeze through irritant
      or allergenic mechanisms, little is known about the differential effects of
      indoor and outdoor fungi on early-life wheeze. METHODS: In a Boston prospective
      birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and
      outdoor air were measured at the age of 2-3 months. Wheeze was determined using
      bimonthly telephone questionnaires. Odds ratios were estimated for an
      interquartile increase in fungal natural log-transformed concentrations,
      adjusting for predictors of wheeze and potential confounders. RESULTS: Increased
      odds of 'any wheeze' (>=1 vs 0 episodes) by age one were positively associated
      with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval
      (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR =
      1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor
      air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were
      protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (>=2 vs <2 episodes) by
      age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and
      indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was
      associated with any wheeze for children with maternal mold sensitization [OR =
      9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR =
      1.32; (0.79-2.20)]. CONCLUSIONS: While wheeze rates were higher with exposures to
      fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts
      in the home had a strong protective association with wheeze in infancy. Molecular
      microbiologic studies may elucidate specific components of innate microbiologic
      stimulants that lead to contrasting effects on wheeze development.

PMID- 24118033
TI  - Marteiliosis in mussels: a rare disease?
AB  - Among 1280 cultured and wild adult Mediterranean mussels, Mytilus
      galloprovincialis, collected over a 1-year surveillance period from the Slovene
      Adriatic Sea, 0.3% were histologically positive for the presence of Marteilia
      spp. The infection was concentrated in winter. Employing the molecular methods of
      PCR, cloning, DNA restriction and sequencing, only Marteilia refringens type M
      was detected in all the infected mussels. Although all life-cycle stages of M.
      refringens severely infected digestive glands, only sporadic disruption of
      epithelial cells of digestive tubules and focal destruction of digestive tubules
      were observed in the infected mussels. This was the first detection of M.
      refringens in M. galloprovincialis from the Slovene Adriatic Sea with the lowest
      prevalence reported to date. In addition, our results highlight the need for
      sequencing to complement the established PCR-RFLP analysis for correct parasite
      typing. 

PMID- 24118034
TI  - The alternative respiratory pathway mediates carboxylate synthesis in white lupin
      cluster roots under phosphorus deprivation.
AB  - Plant adaptations associated with a high efficiency of phosphorus (P) acquisition
      can be used to increase productivity and sustainability in a world with a growing
      population and decreasing rock phosphate reserves. White lupin (Lupinus albus)
      produces cluster roots that release carboxylates to efficiently mobilize P from P
      sorbing soils. It has been hypothesized that an increase in the activity of the
      alternative oxidase (AOX) would allow for the mitochondrial oxidation of NAD(P)H
      produced during citrate synthesis in cluster roots at a developmental stage when
      there is a low demand for ATP. We used the oxygen-isotope fractionation technique
      to study the in vivo respiratory activities of the cytochrome oxidase pathway
      (COP) and the alternative oxidase pathway (AOP) in different root sections of
      white lupins grown hydroponically with and without P. In parallel, AOX protein
      levels and internal carboxylate concentrations were determined in cluster and non
      cluster roots. Higher in vivo AOP activity was measured in cluster roots when
      malate and citrate concentrations were also high, thus confirming our hypothesis.
      AOX protein levels were not always correlated with in vivo AOP activity,
      suggesting post-translational regulation of AOX.

PMID- 24118035
TI  - Salami slicing and the SPU: Publish or Perish?

PMID- 24118037
TI  - Winners in the 2012 Naylor prize competition.

PMID- 24118038
TI  - (131)I-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic
      review and meta-analysis.
AB  - BACKGROUND: (131)I-MIBG therapy can be used for palliative treatment of malignant
      paraganglioma and phaeochromocytoma. The main objective of this study was to
      perform a systematic review and meta-analysis assessing the effect of (131)I-MIBG
      therapy on tumour volume in patients with malignant
      paraganglioma/phaeochromocytoma. METHODS: A literature search was performed in
      December 2012 to identify potentially relevant studies. Main outcomes were the
      pooled proportions of complete response, partial response and stable disease
      after radionuclide therapy. A meta-analysis was performed with an exact
      likelihood approach using a logistic regression with a random effect at the study
      level. Pooled proportions with 95% confidence intervals (CI) were reported.
      RESULTS: Seventeen studies concerning a total of 243 patients with malignant
      paraganglioma/phaeochromocytoma were treated with (131)I-MIBG therapy. The mean
      follow-up ranged from 24 to 62 months. A meta-analysis of the effect of (131)I
      MIBG therapy on tumour volume showed pooled proportions of complete response,
      partial response and stable disease of, respectively, 0.03 (95% CI: 0.06-0.15),
      0.27 (95% CI: 0.19-0.37) and 0.52 (95% CI: 0.41-0.62) and for hormonal response
      0.11 (95% CI: 0.05-0.22), 0.40 (95% CI: 0.28-0.53) and 0.21 (95% CI: 0.10-0.40),
      respectively. Separate analyses resulted in better results in hormonal response
      for patients with paraganglioma than for patients with phaeochromocytoma.
      CONCLUSIONS: Data on the effects of (131)I-MIBG therapy on malignant
      paraganglioma/phaeochromocytoma suggest that stable disease concerning tumour
      volume and a partial hormonal response can be achieved in over 50% and 40% of
      patients, respectively, treated with (131)I-MIBG therapy. It cannot be ruled out
      that stable disease reflects not only the effect of MIBG therapy, but also
      (partly) the natural course of the disease.

PMID- 24118039
TI  - An examination of information quality as a moderator of accurate personality
      judgment.
AB  - Information quality is an important moderator of the accuracy of personality
      judgment, and this article describes research focusing on how specific kinds of
      information are related to accuracy. In this study, 228 participants (159 female,
      69 male; mean age = 23.43; 86.4% Caucasian) in unacquainted dyads were assigned
      to discuss thoughts and feelings, discuss behaviors, or engage in behaviors.
      Interactions lasted 25-30 min, and participants provided ratings of their
      partners and themselves following the interaction on the Big Five traits, ego
      control, and ego-resiliency. Next, the amount of different types of information
      made available by each participant was objectively coded. The accuracy criterion,
      composed of self- and acquaintance ratings, was used to assess distinctive and
      normative accuracy using the Social Accuracy Model. Participants in the
      discussion conditions achieved higher distinctive accuracy than participants who
      engaged in behaviors, but normative accuracy did not differ across conditions.
      Information about specific behaviors and general behaviors were among the most
      consistent predictors of higher distinctive accuracy. Normative accuracy was more
      likely to decrease than increase when higher-quality information was available.
      Verbal information about behaviors is the most useful for learning about how
      people are unique.

PMID- 24118040
TI  - Providing lipid-based nutrient supplements does not affect developmental
      milestones among Malawian children.
AB  - AIM: To assess whether using lipid-based nutrient supplements (LNS) to complement
      the diets of infants and young children affected when they achieved selected
      developmental milestones. METHODS: In rural Malawi, 840 6-month-old healthy
      infants were enrolled to a randomised trial. Control participants received no
      supplements, others were provided with milk-containing LNS, soy-containing LNS or
      corn-soy blend (CSB) for 12 months. Outcomes were the age at which they achieved
      key milestone: motor (walking with assistance, standing and walking alone,
      running), social (drinking from a cup and eating by themselves) and language
      (saying single comprehensible words and waving goodbye). RESULTS: The mean age at
      which the subjects walked with assistance was 42.5, 42.3, 42.7 and 43.2 weeks in
      the control, milk-LNS, soy-LNS and CSB groups, respectively (p = 0.748). There
      were also no significant differences in the mean age at standing alone (45.0,
      44.9, 45.1 and 46.3 weeks), walking alone (54.6, 55.1, 55.3, 56.5 weeks), running
      (64.6, 63.7, 64.8, 65.9 weeks) or any other social or language milestones (each p
      > 0.10). CONCLUSION: The findings do not support a hypothesis that providing
      tested formulations and doses of micronutrient-fortified LNS or CSB would have an
      impact on when young children in rural Malawi achieved selected developmental
      milestones.

PMID- 24118041
TI  - Avidity and positive allosteric modulation/cooperativity act hand in hand to
      increase the residence time of bivalent receptor ligands.
AB  - Bivalent ligands bear two target-binding pharmacophores. Their simultaneous
      binding increases their affinity (avidity) and residence time. They become
      'bitopic' when the binding sites at the target permit the pharmacophores the
      exert allosteric modulation of each other's affinity and/or activity. Present
      simulations reveal that positive cooperativity exacerbates these phenomena,
      whereas negative cooperativity curtails them, irrespective of whether the
      association or dissociation rates of the individual pharmacophores are affected.
      Positive cooperativity delays the attainment of equilibrium binding, yielding
      'hemi-equilibrium' conditions and only apparent affinity constants under usual
      experimental conditions. Monovalent ligands that bind to one of the target sites
      decrease the bitopic ligand's residence time concentration-wise; their potency
      depends on their association rate and thereon acting cooperativity rather than on
      affinity. This stems from the repetitive, very fast reformation of fully bound
      bitopic ligand-target complexes by rebinding of freshly dissociated
      pharmacophores. These studies deal with kinetic binding properties (of increasing
      interest in pharmacology) of bitopic ligands (a promising avenue in medicinal
      chemistry). 

PMID- 24118042
TI  - Value of wash-in and wash-out time in the diagnosis between hepatocellular
      carcinoma and other hepatic nodules with similar vascular pattern on contrast
      enhanced ultrasound.
AB  - BACKGROUND AND AIM: The study aims to demonstrate whether the wash-in and wash
      out time can be reliable as a criterion in the differential diagnosis between
      hepatocellular carcinoma (HCC) and other hepatic nodules with vascular pattern
      similar to HCC on contrast-enhanced ultrasound (CEUS). METHODS: From February
      2012 to February 2013, 214 patients with hepatic nodules displayed rapid
      hyperenhancement and quick wash-out on CEUS were included in this study. Before
      performing CEUS, all nodules were examined by grayscale ultrasonography and color
      Doppler techniques. CEUS was performed with SonoVue and low mechanical index
      technique. The initial time to enhancement, time to peak, time of the nodule
      being hypoenhanced were comparatively studied between HCCs and other hepatic
      nodules. RESULTS: Of all the 214 nodules, 209 were malignant (164 HCCs, 31
      metastases, 10 intrahepatic cholangiocarcinomas (ICCs), 3 combined hepatocellular
      cholangiocarcinomas, 1 epithelioid hemangioendothelioma), and five were benign
      (two inflammatory pseudotumors, one focal nodular hyperplasia nodule, one
      hemangioma, and one hyperplastic nodule). Metastases and ICCs showed more rapid
      wash-out than HCCs (P < 0.05): 16 of 31 metastases and 7 of all ICCs showed wash
      out by 40 s after injection. CONCLUSIONS: Some focal liver lesions can show
      enhancement pattern similar to HCCs on CEUS. The wash-out time may be useful in
      the differential diagnosis.

PMID- 24118043
TI  - Left atrial reverse remodeling following valve surgery for chronic degenerative
      mitral regurgitation in patients with preoperative sinus rhythm: effects on long
      term outcome.
AB  - BACKGROUND AND AIM OF STUDY: Chronic degenerative mitral regurgitation (MR) with
      left atrial (LA) enlargement is predictive of adverse cardiovascular events
      including stroke, atrial fibrillation (AF), and impaired survival. Mitral valve
      surgery (MVS) initiates left atrial reverse remodeling (LARR) characterized by LA
      volume reduction and improved function. The aim of this study was to evaluate the
      effects of LARR on clinical outcome in patients with and without LARR following
      MVS. METHODS: A retrospective study was conducted of 137 consecutive patients in
      sinus rhythm with degenerative severe MR undergoing isolated MVS. The left atrial
      volume index (LAVi) was assessed by studying pre- and postoperative
      echocardiograms; LARR was defined as a reduction in LAVi >= 15%. Clinical outcome
      was evaluated in relation to the absolute and relative reduction in LAVi, and the
      presence or absence of postoperative LARR. RESULTS: The incidence of
      postoperative LARR was 74% (n = 101). The overall 90-day survival was 100%.
      Freedom from complications and cardiac events 10 years after surgery for patients
      with LARR versus those without was: 92 +/- 4% versus 66 +/- 13% (p = 0.088) for
      mortality; 72 +/- 1% versus 51 +/- 18% (p = 0.131) for new onset of chronic AF;
      72 +/- 1% versus 81 +/- 6% (p = 0.477) for cerebral thromboembolism; and 50 +/-
      10% versus 49 +/- 11% (p = 0.744) for major cardiac adverse events. CONCLUSIONS:
      Preoperative LA enlargement due to severe degenerative MR in patients with sinus
      rhythm demonstrates a high potential for postoperative reverse remodeling
      following MVS. The absence of postoperative LARR was not associated with an
      increase in the risk of postoperative mortality or adverse clinical events.

PMID- 24118044
TI  - Occupational therapy services for people with autism spectrum disorders: current
      state of play, use of evidence and future learning priorities.
AB  - BACKGROUND: A dramatic increase in the prevalence of autism spectrum disorders
      and increased funding to support children with autism spectrum disorders have
      added to the demand for occupational therapy services. This study explored
      current practices and future learning priorities of Queensland occupational
      therapists who work in this field. METHOD: A survey in relation to occupational
      therapy services for people with autism spectrum disorders was distributed to all
      registered Queensland occupational therapists (N=2547). The development of the
      survey was informed by a series of focus groups comprising occupational therapy
      clinicians, supervisors and academics. The survey covered demographics, caseload
      composition, collaboration, context/setting, service-delivery models, information
      gathering, goal setting, interventions, perceived challenges and confidence, use
      of evidence, and experience of professional development and support, and future
      learning priorities. RESULTS: Of 818 surveys returned, 235 respondents provided
      services to clients with autism spectrum disorders, with young children being
      more likely to receive a service than adolescents or adults. A pervasive focus on
      sensory processing was apparent in relation to assessment, intervention, and key
      areas of knowledge. Around half the respondents indicated that they lacked
      confidence at least some of the time. Autism spectrum disorders-specific
      experience was a significant predictor of confidence. Many therapists reported
      challenges in finding useful information in the literature and reliance on
      conferences or workshops as their main source of evidence. Commonly identified
      learning priorities included new developments in the field, early intervention,
      school support, sensory processing and clinical reasoning. CONCLUSION: This
      research highlights the need for comprehensive autism spectrum disorders
      specific, face-to-face training focusing on evidence-based and occupation-centred
      practices.

PMID- 24118045
TI  - Time-dependent reduction of structural complexity of the buccal epithelial cell
      nuclei after treatment with silver nanoparticles.
AB  - Recent studies have suggested that silver nanoparticles (AgNPs) may affect cell
      DNA structure in in vitro conditions. In this paper, we present the results
      indicating that AgNPs change nuclear complexity properties in isolated human
      epithelial buccal cells in a time-dependent manner. Epithelial buccal cells were
      plated in special tissue culture chamber / slides and were kept at 37 degrees C
      in an RPMI 1640 cell culture medium supplemented with L-glutamine. The cells were
      treated with colloidal silver nanoparticles suspended in RPMI 1640 medium at the
      concentration 15 mg L-1. Digital micrographs of the cell nuclei in a sample of 30
      cells were created at five different time steps: before the treatment (controls),
      immediately after the treatment, as well as 15 , 30 and 60 min after the
      treatment with AgNPs. For each nuclear structure, values of fractal dimension,
      lacunarity, circularity, as well as parameters of grey level co-occurrence matrix
      (GLCM) texture, were determined. The results indicate time-dependent reduction of
      structural complexity in the cell nuclei after the contact with AgNPs. These
      findings further suggest that AgNPs, at concentrations present in today's over
      the-counter drug products, might have significant effects on the cell genetic
      material.

PMID- 24118046
TI  - Spontaneous tear in the noncoronary cusp of the medtronic freestyle
      bioprosthesis.

PMID- 24118048
TI  - Spectral and Spatial UV Sky Radiance Measurements at a Seaside Resort Under Clear
      Sky and Slightly Overcast Conditions.
AB  - Spatial measurements of the diffusely scattered sky radiance at a seaside resort
      under clear sky and slightly overcast conditions have been used to calculate the
      sky radiance distribution across the upper hemisphere. The measurements were done
      in the summer season when solar UV radiation is highest. The selected wavelengths
      were 307, 350 and 550 nm representing the UVB, UVA and VIS band. Absolute values
      of radiance differ considerably between the wavelengths. Normalizing the measured
      values by use of direct solar radiance made the spatial distributions of unequal
      sky radiance comparable. The results convey a spatial impression of the different
      distributions of the radiance at the three wavelengths. Relative scattered
      radiance intensity is one order of magnitude greater in UVB than in VIS, whereas
      in UVA lies roughly in between. Under slightly overcast conditions scattered
      radiance is increased at all three wavelengths by about one order of magnitude.
      These measurements taken at the seaside underline the importance of diffuse
      scattered radiance. The effect of shading parts of the sky can be estimated from
      the distribution of sky radiance. This knowledge might be useful for sun seekers
      and in the treatment of people staying at the seaside for therapeutic purposes.

PMID- 24118047
TI  - A model-based approach for the evaluation of once daily dosing of lamivudine in
      HIV-infected children.
AB  - AIM: Little attention has been paid to the effects of compliance and prescription
      practice on treatment outcome in HIV-infected children. In this context, an
      evaluation of the role of covariates on pharmacokinetics is required to establish
      the impact of differences in dosing regimens. Here we investigate whether a once
      daily dosing regimen of lamivudine provides comparable exposure to the currently
      approved paediatric regimen. METHODS: A hypothetical group of 180 patients
      between 3 months and 12 years old was used to evaluate the impact of body weight
      on systemic exposure to lamivudine. Simulation scenarios were evaluated using AUC
      and Cmax as parameters of interest. The analysis was performed using a population
      pharmacokinetic model previously implemented in nonmem v.6.2. RESULTS: The
      simulations show that once daily dosing of lamivudine yields comparable exposure
      to historical values observed in children and adults, both for liquid and solid
      dosage forms. Simulated steady-state AUC(0-24 h) and Cmax values after once daily
      doses ranged respectively from 9.9  mg l-1  h and 1.9 mg l-1 for children lighter
      than 14 kg to 13.75 mg l-1  h and 3.0 mg l-1 for children heavier than 30 kg.
      These values are comparable or higher than historical values observed after once
      daily dosing in children and adults. CONCLUSIONS: Our findings illustrate how
      dosing regimens can be evaluated taking into account the effects of developmental
      growth on drug disposition. Most importantly, they suggest that the reduction in
      dosing frequency to once daily leads to comparable lamivudine exposure, as
      observed after administration of a twice daily dosing regimen.

PMID- 24118049
TI  - Aplasia cutis congenita in a setting of fetus papyraceus associated with small
      fetal abdominal circumference and high alpha-fetoprotein and amniotic
      acetylcholinesterase.
AB  - Fetus papyraceus is the fetal death of one or more fetuses in a multiparous
      pregnancy. The surviving infants can experience extensive aplasia cutis in an H
      shaped distribution over the flanks and abdomen as a consequence of the loss of
      their fetal sibling. We report the case of a monochorionic, diamniotic pregnancy
      complicated by a single fetal death at 13 weeks of gestational age. Aplasia cutis
      of the surviving twin was suggested in utero by three criteria: high amniotic and
      maternal alpha-fetoprotein, detectable acetylcholinesterase, and small abdominal
      circumference on prenatal ultrasound. This constellation of findings in the
      setting of fetus papyraceus can be an indicator of aplasia cutis in the surviving
      fetus.

PMID- 24118050
TI  - The development of leadership outcome-indicators evaluating the contribution of
      clinical specialists and advanced practitioners to health care: a secondary
      analysis.
AB  - AIMS: To report a secondary analysis of data collected from the case study phase
      of a national study of advanced practitioners and to develop leadership outcome
      indicators appropriate for advanced practitioners. BACKGROUND: In many countries,
      advanced practitioners in nursing and midwifery have responsibility as leaders
      for health care development, but without having leadership outcome measures
      available they are unable to demonstrate the results of their activities. In
      Ireland, a sequential mixed method research study was used to develop a validated
      tool for the evaluation of clinical specialists and advanced practitioners.
      Despite strong evidence of leadership activities, few leadership-specific
      outcomes were generated from the primary analysis. DESIGN: Secondary analysis of
      a multiple case study data set. METHODS: Data set comprised 23 case studies of
      advanced practitioner/clinical specialists from 13 sites across each region in
      Ireland from all divisions of the Nursing Board Register. Data were collected
      2008-2010. Data sources included non-participant observation (n = 92 hours) of
      advanced practitioners in practice, interviews with clinicians (n = 21), patients
      (n = 20) and directors of nursing/midwifery (n = 13) and documents. Analysis
      focused on leadership outcome-indicator development in line with the National
      Health Service's Good Indicators Guide. RESULTS: The four categories of
      leadership outcomes for advanced practitioner developed were as follows: (i)
      capacity and capability building of multidisciplinary team; (ii) measure of
      esteem; (iii) new initiatives for clinical practice and healthcare delivery; and
      (iv) clinical practice based on evidence. CONCLUSIONS: The proposed set of
      leadership outcome-indicators derived from a secondary analysis captures the
      complexity of leadership in practice. They add to existing clinical outcomes
      measuring advanced practice.

PMID- 24118051
TI  - Review article: the association of diet with onset and relapse in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: The role of diet in inflammatory bowel disease (IBD) is supported by
      migration studies and increasing incidences in line with Westernisation. AIM: To
      give a complete overview of studies associating habitual diet with the onset or
      relapses in ulcerative colitis (UC) or Crohn's disease (CD). METHODS: A
      structured search in Pubmed, the Cochrane Library and EMBASE was performed using
      defined key words, including only full text papers in English language. RESULTS:
      Forty-one studies were identified, investigating onset (n = 35), relapses (n = 5)
      or both (n = 1). Several studies reported high intake of sugar or sugar
      containing foods (n = 7 UC, n = 12 CD), and low intake of fruits and/or
      vegetables (n = 5 UC, n = 10 CD) to be associated with an increased onset risk.
      However, these findings could not be confirmed by similar or higher numbers of
      other studies. A possible protective role was found for grain-derived products in
      CD onset, but results were inconsistent for dietary fibre in UC and CD and grain
      derived products in UC. No definite conclusions could be drawn for unsaturated
      fatty acids (UFA), protein and energy intake due to limited and/or inconsistent
      results. Six studies reported on diet and relapse risk, of which only two (n = 1
      UC, n = 1 CD) had a prospective follow-up. CONCLUSIONS: The current evidence is
      not sufficient to draw firm conclusions on the role of specific food components
      or nutrients in the aetiology of IBD. Furthermore, large prospective studies into
      the role of habitual diet as a trigger of relapses are needed, to identify new
      therapeutic or preventive targets.

PMID- 24118052
TI  - Cap polyposis and colitis cystica profunda: a rare association.

PMID- 24118053
TI  - Nasal hyper-reactivity is a common feature in both allergic and nonallergic
      rhinitis.
AB  - BACKGROUND: Nasal hyper-reactivity is an increased sensitivity of the nasal
      mucosa to various nonspecific stimuli. Both allergic rhinitis (AR) and
      nonallergic rhinitis (NAR) patients can elicit nasal hyper-reactivity symptoms.
      Differences in the prevalence or type of nasal hyper-reactivity in AR and NAR
      patients are largely unknown. In this study, we quantitatively and qualitatively
      assessed nasal hyper-reactivity in AR and NAR. METHODS: In the first part, an
      analysis of a prospectively collected database was performed to reveal patient
      reported symptoms of hyper-reactivity. In the second part, cold dry air
      provocation (CDA) was performed as a hyper-reactivity measure in AR and NAR
      patients and healthy controls, and symptoms scores, nasal secretions and peak
      nasal inspiratory flow were measured. Comparisons were made between AR and NAR
      patients in both studies. RESULTS: The database analysis revealed high hyper
      reactivity prevalence in AR (63.4%) and NAR (66.9%). There were no differences
      between AR and NAR in terms of the number or type of hyper-reactivity stimuli.
      Hyper-reactivity to physical stimuli did not exclude a response to chemical
      stimuli, or vice versa. CDA provocation resulted in a significant increase in
      rhinitis symptoms and the amount of nasal secretions in AR and NAR patients, but
      not in controls. CONCLUSIONS: We found no quantitative or qualitative differences
      in nasal hyper-reactivity between AR and NAR patients. It is not possible to
      differentiate NAR subpopulations based on physical or chemical stimuli.

PMID- 24118054
TI  - Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion
      molecule L1 to promote neuronal and Schwann cell migration as well as
      myelination.
AB  - The cell adhesion molecule L1 regulates cellular responses in the developing and
      adult nervous system. Here, we show that stimulation of cultured mouse cerebellar
      neurons by a function-triggering L1 antibody leads to cathepsin E-mediated
      generation of a sumoylated 30 kDa L1 fragment (L1-30) and to import of L1-30 into
      the nucleus. Mutation of the sumoylation site at K1172 or the cathepsin E
      cleavage site at E1167 abolishes generation of L1-30, while mutation of the
      nuclear localization signal at K1147 prevents nuclear import of L1-30. Moreover,
      the aspartyl protease inhibitor pepstatin impairs the generation of L1-30 and
      inhibits L1-induced migration of cerebellar neurons and Schwann cells as well as
      L1-dependent in vitro myelination on axons of dorsal root ganglion neurons by
      Schwann cells. L1-stimulated migration of HEK293 cells expressing L1 with mutated
      cathepsin E cleavage site is diminished in comparison to migration of cells
      expressing non-mutated L1. In addition, L1-stimulated migration of HEK293 cells
      expressing non-mutated L1 is also abolished upon knock-down of cathepsin E
      expression and enhanced by over-expression of cathepsin E. The findings of the
      present study indicate that generation and nuclear import of L1-30 regulate
      neuronal and Schwann cell migration as well as myelination. Cell adhesion
      molecule L1 regulates cellular responses in the developing and adult nervous
      system. L1 stimulation triggers sumoylation and cleavage of L1, thus generating
      the L1-70 fragment (1) which is cleaved by cathepsin E (2) yielding the L1-30
      fragment that is imported to the nucleus (3), may bind to DNA and/or nuclear
      proteins (4), to regulate diverse cellular functions. 

PMID- 24118055
TI  - The effects of xenon and nitrous oxide gases on alcohol relapse.
AB  - BACKGROUND: In recent years, the glutamate theory of alcoholism has emerged as a
      major theory in the addiction research field and N-methyl-d-aspartate (NMDA)
      receptors have been shown to play a major role in alcohol craving and relapse.
      The NMDA receptors are considered as the primary side of action of the anesthetic
      gases xenon (Xe) and nitrous oxide (N2 O). Despite the rapid on/off kinetics of
      these gases on the NMDA receptor, a brief gas exposure can induce an analgesic or
      antireward effect lasting several days. The aim of this study was to examine the
      effect of both Xe and N2 O on alcohol-seeking and relapse-like drinking behavior
      (measured as the alcohol deprivation effect) in Wistar rats. METHODS: We used 2
      standard procedures-the alcohol deprivation model with repeated deprivation
      phases and the cue-induced reinstatement model of alcohol seeking-to study the
      effect of 2 brief gas exposures of either Xe, N2 O, or control gas on relapse
      like drinking and alcohol-seeking behavior. RESULTS: Here, we show that exposure
      to Xe during the last 24 hours of abstinence produced a trend toward reduced
      ethanol intake during the first alcohol re-exposure days. In addition, Xe gas
      exposure significantly decreased the cue-induced reinstatement of alcohol-seeking
      behavior. N2 O had no effect on either behavior. CONCLUSIONS: Xe reduces alcohol
      seeking behavior in rats and may therefore also interfere with craving in human
      alcoholics.

PMID- 24118056
TI  - Induction of Treg cells after oral immunotherapy in hen's egg-allergic children.

PMID- 24118057
TI  - Association between perioral muscle pressure and masticatory performance.
AB  - The aim of this study was to determine the association between strength of the
      perioral muscles and masticatory performance. Subjects were 56 healthy adults (30
      men and 26 women; mean age of 24.9 years) with normal occlusion. Perioral muscle
      pressure was measured using JMS tongue pressure measurement device, and maximum
      tongue pressure and cheek pressure on the habitual chewing side (H) and non
      habitual side (non-H) were measured. The masticatory performance was evaluated
      using gummy jelly, and the amount of glucose extracted was measured after chewing
      under condition H or non-H. The association between sex and maximum tongue
      pressure was analysed using Student's t-test. Cheek pressure and the amount of
      the glucose extracted between condition H and non-H or between men and women were
      analysed by two-way repeated-measures anova. In addition, the correlations
      between maximum tongue pressure and cheek pressure on condition H, maximum tongue
      pressure and the amount of glucose extracted under condition H, and cheek
      pressure and the amount of glucose extracted under condition H were analysed
      using Pearson's correlation coefficients for men and women. The maximum tongue
      pressure, cheek pressure and the amount of glucose extracted were higher in men
      than in women. The amount of glucose extracted was higher under condition H than
      under condition non-H, but no significant difference in chewing side was observed
      in cheek pressure between men and women. Additionally, positive correlations were
      shown between maximum tongue pressure, habitual-side cheek pressure and the
      amount of glucose extracted on men and women. In conclusion, the association
      between higher perioral muscle pressure and better masticatory performance was
      shown. 

PMID- 24118058
TI  - Characteristics of girls with pituitary hyperplasia and sexual precocity
      secondary to primary hypothyroidism.
AB  - AIM: To investigate the different characteristics of girls with pituitary
      hyperplasia secondary to primary hypothyroidism (PPH), with and without sexual
      precocity. METHODS: Pituitary hyperplasia secondary to primary hypothyroidism
      girls were divided into two groups: group A, with sexual precocity (n = 8), and
      group B, without sexual precocity (n = 14). The following values were measured
      before and after 3 months levothyroxine therapy: free triiodothyronine (FT3 ),
      free thyroxine (FT4 ), thyrotropin (TSH), follicle-stimulating hormone (FSH),
      luteinising hormone (LH), prolactin (PRL), estradiol (E2 ), testosterone (T),
      pituitary height, uterine volume (UV), ovarian volume (OV) and follicular
      diameter (FD). RESULTS: Thyrotropin, FSH, PRL, E2 , T, pituitary height, UV, OV
      and FD were higher in group A than group B (all p < 0.05); FT3 , FT4 and LH
      levels were not different (all p > 0.05). In all of the PPH girls, pituitary
      height was correlated with FT3 , FT4 and PRL (r = -0.545, p = 0.009, r = -0.567,
      p = 0.006 and r = 0.666, p = 0.001, respectively). PRL was positively correlated
      with UV, FD and FSH (r = 0.581, p = 0.005, r = 0.482, p = 0.031 and r = 0.667, p
      = 0.001, respectively), and FSH was positively correlated with OV (r = 0.522, p =
      0.013). These abnormalities regressed after therapy. CONCLUSION: Pituitary
      hyperplasia secondary to primary hypothyroidism girls with sexual precocity have
      increased plasma TSH, FSH, PRL, E2 and T levels, pituitary height and uterine,
      ovarian and follicular size.

PMID- 24118059
TI  - Thermophilic lignocellulose deconstruction.
AB  - Thermophilic microorganisms are attractive candidates for conversion of
      lignocellulose to biofuels because they produce robust, effective, carbohydrate
      degrading enzymes and survive under harsh bioprocessing conditions that reflect
      their natural biotopes. However, no naturally occurring thermophile is known that
      can convert plant biomass into a liquid biofuel at rates, yields and titers that
      meet current bioprocessing and economic targets. Meeting those targets requires
      either metabolically engineering solventogenic thermophiles with additional
      biomass-deconstruction enzymes or engineering plant biomass degraders to produce
      a liquid biofuel. Thermostable enzymes from microorganisms isolated from diverse
      environments can serve as genetic reservoirs for both efforts. Because of the
      sheer number of enzymes that are required to hydrolyze plant biomass to
      fermentable oligosaccharides, the latter strategy appears to be the preferred
      route and thus has received the most attention to date. Thermophilic plant
      biomass degraders fall into one of two categories: cellulosomal (i.e. multienzyme
      complexes) and noncellulosomal (i.e. 'free' enzyme systems). Plant-biomass
      deconstructing thermophilic bacteria from the genera Clostridium (cellulosomal)
      and Caldicellulosiruptor (noncellulosomal), which have potential as metabolic
      engineering platforms for producing biofuels, are compared and contrasted from a
      systems biology perspective. 

PMID- 24118060
TI  - Inferring community dynamics of organohalide-respiring bacteria in chemostats by
      covariance of rdhA gene abundance.
AB  - We have developed a novel approach to identifying and quantifying closely related
      organohalide-respiring bacteria. Our approach made use of the unique genomic
      associations of specific reductive dehalogenase subunit A encoding genes (rdhA)
      that exist in known strains of Dehalococcoides mccartyi and Desulfitobacterium
      and the distinguishing covariance pattern of observed rdhA genes to assign genes
      to unknown strains. To test this approach, we operated five anaerobic reductively
      dechlorinating chemostats for 3-4 years with tetrachloroethene and
      trichloroethene as terminal electron acceptors and lactate/formate as electron
      donors. The presence and abundance of rdhA genes were determined comprehensively
      at the community level using a custom-developed Reductive Dehalogenase Chip (RDH
      Chip) DNA microarray and used to define putative strains of Dehalococcoides
      mccartyi and Desulfitobacterium sp. This monitoring revealed that stable chemical
      performance of chemostats was reflected by a stable community of reductively
      dechlorinating bacteria. However, perturbations introduced by, for example,
      electron donor limitation or addition of the competing electron acceptor sulfate
      led to overall changes in the chemostat performance, including incomplete
      reduction in the chloroethene substrates, and in the population composition of
      reductively dehalogenating bacteria. Interestingly, there was a high diversity of
      operationally defined D. mccartyi strains between the chemostats with almost all
      strains unique to their specific chemostats in spite of similar selective
      pressure and similar inocula shared between chemostats. 

PMID- 24118061
TI  - Age versus stage: does ontogeny modify the effect of phosphorus and arbuscular
      mycorrhizas on above- and below-ground defence in forage sorghum?
AB  - Arbuscular mycorrhizas (AM) can increase plant acquisition of P and N. No
      published studies have investigated the impact of P and AM on the allocation of N
      to the plant defence, cyanogenic glucosides. We investigated the effects of soil
      P and AM on cyanogenic glucoside (dhurrin) concentration in roots and shoots of
      two forage sorghum lines differing in cyanogenic potential (HCNp). Two harvest
      times allowed plants grown at high and low P to be compared at the same age and
      the same size, to take account of known ontogenetic changes in shoot HCNp. P
      responses were dependent on ontogeny and tissue type. At the same age, P-limited
      plants were smaller and had higher shoot HCNp but lower root HCNp.
      Ontogenetically controlled comparisons showed a P effect of lesser magnitude, and
      that there was also an increase in the allocation of N to dhurrin in shoots of P
      limited plants. Colonization by AM had little effect on shoot HCNp, but increased
      root HCNp and the allocation of N to dhurrin in roots. Divergent responses of
      roots and shoots to P, AM and with ontogeny demonstrate the importance of
      broadening the predominantly foliar focus of plant defence studies/theory, and of
      ontogenetically controlled comparisons.

PMID- 24118062
TI  - A randomised trial to evaluate the effects of low-dose aspirin in gestation and
      reproduction: design and baseline characteristics.
AB  - BACKGROUND: Low-dose aspirin (LDA) has been proposed to improve pregnancy
      outcomes in couples experiencing recurrent pregnancy loss. However, results from
      studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most
      studies evaluated LDA-initiated post-conception. The purpose of the Effects of
      Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether
      preconception-initiated LDA improves livebirth rates in women with one to two
      prior losses. METHODS: We performed a multicentre, block randomised, double
      blind, placebo-controlled trial. Study participants were recruited using
      community-based advertisements and physician referral to four university medical
      centres in the US (2006-12). Eligible women were aged 18-40 years actively trying
      to conceive, with one to two prior losses. Participants were randomised to
      receive daily LDA (81 mg/day) or a matching placebo, and all were provided with
      daily 400-mcg folic acid. Follow-up continued for <=6 menstrual cycles while
      attempting to conceive. For those who conceived, treatment was continued until 36
      weeks gestation. The primary outcome was the cumulative livebirth rate over the
      trial period. RESULTS: There were 1228 women randomised (615 LDA, 613 placebo).
      Participants had a mean age of 28.7, were mostly white (95%), well educated (86%
      more than high school education), and employed (75%) with a household income
      >$100 000 annually (40%). The characteristics of those in the treatment and
      placebo arms were well balanced. CONCLUSIONS: We describe the study design,
      recruitment, data collection, and baseline characteristics of participants
      enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and
      other pregnancy outcomes in these women.

PMID- 24118064
TI  - What are the causes of the ill effects of chronic hemodialysis? The burden of
      vascular access.

PMID- 24118063
TI  - Effect of telmisartan on levels of IL-1, TNF-alpha, down-regulated COX-2, MMP-2,
      MMP-9 and RANKL/RANK in an experimental periodontitis model.
AB  - AIM: The aim of this study was to evaluate the effect of telmisartan (TELM) on
      inflammation, oxidation and the expression of matrix metalloproteinases (MMPs)
      and the expression RANKL/RANK/OPG in the periodontal tissue of a rat model for
      ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats
      were randomly divided into five groups of 10 rats each: (i) non-ligated, given
      water; (ii) ligated, given water; (iii) ligated, given 1 mg/kg TELM; (iv)
      ligated, given 5 mg/kg TELM; and (v) ligated, given 10 mg/kg TELM. All groups
      were treated with saline or TELM for 10 days. Periodontal tissue was analysed by
      histopathology; by the immunohistochemical examination of COX-2, MMP-2, MMP-9 and
      the RANKL/RANK/OPG pathway; and by ELISA analysis of the levels of IL-1beta, IL
      10, TNF-alpha, myeloperoxidase (MPO), malonaldehyde (MDA) and glutathione (GSH).
      RESULTS: Treatment with 10 mg/kg TELM resulted in reduced concentrations of MPO,
      MDA (p < 0.05) and the pro-inflammatory cytokine IL-1beta (p < 0.05); reduced
      expression of MMP-2, MMP-9, RANK, RANKL and COX-2; and an increase in OPG. The
      levels of TNF-alpha were significantly reduced in all TELM-treated groups.
      CONCLUSIONS: These findings confirm the involvement of TELM in reducing the
      inflammatory response, oxidative stress and bone loss in ligature-induced
      periodontitis in rats.

PMID- 24118065
TI  - Synthesis and adenosine receptors binding affinities of a series of 3
      arylcoumarins.
AB  - OBJECTIVES: In the present communication, we report the synthesis,
      pharmacological evaluation, theoretical evaluation of absorption, distribution,
      metabolism and excretion properties and structure-activity relationship study of
      a selected series of 3-arylcoumarins (compounds 1-9). Adenosine receptors (ARs)
      binding activity and selectivity of the synthesized compounds 1-9 were evaluated
      in this study. Different substituents were introduced in both benzene rings of
      the evaluated scaffold, at positions 6 and 3' or 4' of the moiety. The lack of
      data on the 3-arylcoumarin scaffold encouraged us to explore the ARs' binding
      activity of a selected series of derivatives. METHODS: A new series of coumarins
      (compounds 1-9) were synthesized and evaluated by radioligand binding studies
      towards ARs. KEY FINDINGS: Analysing the experimental data, it can be observed
      that neither the simple 3-arylcoumarin nor the 4'-nitro derivatives presented
      detectable binding affinity for the evaluated receptors, although most of the
      other substituted derivatives have good binding affinity profiles, especially
      against the hA1 /hA3 or only hA3 AR. CONCLUSIONS: The most remarkable derivative
      is compound 2, presenting the best affinity for hA3 AR (Ki  = 2680 nM) and
      significant selectivity for this subtype.

PMID- 24118066
TI  - Cyclodextrins improve oral absorption of a novel factor Xa inhibitor by
      interfering with interaction between the drug and bile acids in rats.
AB  - OBJECTIVES: Poor oral absorption of a factor Xa inhibitor, DX-9065, is partly due
      to the interaction with bile acids in the gastrointestinal tract. The aim of this
      study is to improve the oral bioavailability of DX-9065 by cyclodextrins (CyDs)
      capable of interfering with such interaction. METHODS: The abilities of the CyDs
      to interfere with the interaction between DX-9065 and sodium chenodeoxycholate
      were evaluated using equilibrium dialysis. The interaction between DX-9065 and
      the CyDs was studied spectroscopically. Effects of the CyDs on the oral
      absorption of DX-9065 were examined in rats. KEY FINDINGS: Hydroxypropyl-beta-CyD
      and gamma-CyD were effective in interfering with the interaction between DX-9065
      and sodium chenodeoxycholate as a representative bile acid. Spectroscopic studies
      revealed that DX-9065 was included into the CyD cavity to form inclusion
      complexes in an acidic medium. With dissociation of the carboxyl group of DX-9065
      in a neutral medium, the stability of the complexes was decreased to such an
      extent that DX-9065 in the cavity is replaced with co-existing bile acids. The
      average area under the plasma concentration-time curve value after oral
      administration of DX-9065 with hydroxypropyl-beta-CyD was 2.5 times higher than
      that of DX-9065 alone with a statistical difference in rats. CONCLUSIONS: We
      suggest that the CyDs are useful in designing oral formulations of DX-9065 with
      an improved bioavailability.

PMID- 24118067
TI  - Anti-inflammatory R-prostaglandins from Caribbean Colombian soft coral Plexaura
      homomalla.
AB  - OBJECTIVES: This study aims to evaluate the effect of prostaglandins isolated
      from soft coral Plexaura homomalla, collected in Colombian Caribbean Sea, on in
      vivo and in vitro inflammation models. METHODS: Extracts from P. homomalla were
      fractionated and sequentially chromatographed to obtain the prostaglandins: (15R)
      PGA2 (1), (15R)-PGA2 -Me (2), (15R)-O-Ac-PGA2 (3), (15R)-O-Ac-PGA2 -Me (4) and
      (15R)-PGE2 (5) in addition to three semi-synthetic prostaglandins obtained by
      transformations of the natural products. The anti-inflammatory properties of
      natural and semi-synthetic compounds were determined in vivo using 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema model and in vitro
      leucocyte degranulation, myeloperoxidase (MPO) and elastase enzymatic activities
      from human polymorphonuclear cells (PMNs). The cell viability was evaluated by
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. KEY
      FINDINGS: In the in vivo assay, (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) showed
      anti-inflammatory activity, as well as in vitro inhibition of elastase release
      from PMNs. In the PMNs degranulation assay, (15R)-PGE2 (5), was the most active
      compound in the inhibition of MPO release. Finally, all the tested prostaglandins
      showed moderate inhibition for elastase enzyme activity, whereas none of the
      prostaglandins exhibit significative inhibition on MPO activity. CONCLUSION:
      (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) present significant inhibition on three
      important events related to the topical inflammatory response induced by TPA: the
      oedema formation, the PMNs degranulation, events that modulate MPO and elastase
      levels at inflammation site, and the inhibition of the enzyme activity.

PMID- 24118068
TI  - Endoscopic resection therapies for rectal neuroendocrine tumors: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND AIM: Among various endoscopic resection therapies, including
      conventional endoscopic mucosal resection (EMR) only with a snare after
      submucosal injection, modified EMR (m-EMR) with other assistant devices such as a
      ligation band or a suction cap, and endoscopic submucosal dissection (ESD), we
      aimed to study which is the best choice for rectal neuroendocrine tumors.
      METHODS: A broad literature research was performed, and a systematic review and
      meta-analysis were conducted. RESULTS: Ten retrospective studies with 650
      patients were included. Complete resection rates were significantly higher in the
      ESD group compared with the EMR group (relative risk [RR] 0.89, 95% confidence
      interval [CI] [0.79, 0.99]), in the m-EMR group compared with the conventional
      EMR group (RR 0.72, 95% CI [0.60, 0.86]), and was comparable between the ESD
      group and the m-EMR group (RR 1.03, 95% CI [0.95, 1.11]). Procedure time was
      significantly longer in the ESD group than in the EMR group (standard mean
      differences -1.37, 95% CI [-1.99, -0.75]), but there was no significant
      difference between that of the m-EMR group and ESD group (standard mean
      differences -1.50, 95% CI [-3.14, 0.14]). Local recurrence occurred in five cases
      in the EMR group (5/328) and did not occur in the ESD group (0/209). CONCLUSIONS:
      ESD or m-EMR techniques could be applied to rectal neuroendocrine tumors with
      indications for endoscopic treatment. m-EMR procedures appear to be comparable
      with ESD in the treatment of rectal neuroendocrine tumors. However, the findings
      have to be carefully interpreted due to the lower level of evidence.

PMID- 24118069
TI  - Psychometric evaluation and normative data of the Swedish version of the 10-item
      perceived stress scale.
AB  - The perceived stress scale (PSS) has been translated to several languages and
      validated in many cultures. The longer 14-item version (PSS-14), has been
      translated to Swedish and validated for Swedish use. However, the Swedish version
      of the shorter 10-item version (PSS-10) has not been validated before. Therefore,
      the aim of this study was to evaluate the Swedish version of the PSS-10 with
      regard to reliability and validity, and to provide normative data. Data from
      3,406 individuals who took part in the Vasterbotten Environmental Health Study in
      Sweden were used. The respondents constitute a random sample, aged 18 to 79
      years, and stratified for age and sex. They responded to the Swedish version of
      the PSS-10 as well as to the hospital anxiety and depression scale, and the
      Shirom Melamed burnout questionnaire for assessment of construct validity. The
      results show that the PSS-10 provides approximately normally distributed data,
      has good internal reliability (Cronbach's alpha 0.84), and has good construct
      validity with anxiety (r = 0.68), depression (r = 0.57), and mental/physical
      exhaustion (r = 0.71). The favorable psychometric properties of the Swedish
      version of the PSS-10 suggest use of the instrument for assessing perceived
      stress in Swedish and similar populations. 

PMID- 24118071
TI  - Oncological impact of endoscopic bladder cuff management during
      nephroureterectomy varies according to upper urinary tract tumor location.
AB  - OBJECTIVES: To compare the oncological outcome between extravesical excision and
      transurethral excision for bladder cuff management in patients undergoing
      nephroureterectomy with upper urinary tract urothelial cancer. METHODS: From
      January 2005 to December 2010, 396 patients were enrolled in the present
      retrospective study. Nephroureterectomy was carried out either by endoscopic or
      extravesical bladder cuff excision. The oncological outcome between these two
      procedures was analyzed in patients with different tumor locations. RESULTS: The
      average age of the patients was 66.41 +/- 10.52 years, and the median follow-up
      duration was 40.65 +/- 23.84 months. For upper urinary tract urothelial cancer
      management, extravesical bladder cuff excision was carried out in 240 patients,
      whereas the endoscopic method was carried out in 156 patients. Previous bladder
      cancer is still the most independent predictor for bladder recurrence (P <
      0.001). In addition, endoscopic bladder cuff management for low ureteral tumor
      was also independently associated with more bladder tumor recurrence (P = 0.017).
      Non-organ confined pathological stage still independently predicted metastasis (P
      < 0.001) and cancer-specific death (P < 0.001). CONCLUSIONS: There are similar
      oncological outcomes after nephroureterectomy combined with extravesical or
      endoscopic bladder cuff management for patients with upper urinary tract
      urothelial cancer above the low ureter. However, there is a higher incidence of
      bladder tumor recurrence for the low ureteral tumor after nephroureterectomy with
      endoscopic bladder cuff excision.

PMID- 24118072
TI  - Antihepatitis B therapy: a review of current medications and novel small molecule
      inhibitors.
AB  - There are approximately 350 million hepatitis B virus (HBV) carriers worldwide.
      Chronic HBV infection increases the risk of liver cirrhosis and hepatocellular
      carcinoma. To date, two classes of antiviral drugs have been approved by the Food
      and Drug Administration for the treatment of hepatitis B, immunomodulators
      (interferon [IFN]-alpha and pegylated-interferon [PEG-IFN]-alpha) and
      nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and
      entecavir [ETV]). Of these, ETV, TDF, and PEG-IFN-alpha are the most effective
      and are currently recommended for anti-HBV therapy. However, these therapies are
      less than optimal because of their low rate of viral DNA and surface antigen
      clearance; thus, there exists a significant unmet medical need for safe and
      efficacious new anti-HBV drugs. Covering diverse chemical structures and
      mechanisms of action, non-nucleos(t)ide compounds offer great promise in the
      search for new anti-HBV drugs. This review summarizes the currently approved anti
      HBV drugs and highlights advances in the identification and characterization of
      novel small molecule HBV inhibitors. We discuss the sources, structures, anti-HBV
      effects, mechanisms of action, and potential toxicities of these novel
      inhibitors. 

PMID- 24118073
TI  - Modified bentall procedure with composite biologic grafts.
AB  - OBJECTIVES: The search continues for the ideal composite biologic graft (CBG). We
      have performed aortic root replacements with CBGs, initially with a stented
      pericardial valve in a Valsalva graft (Gen1) and subsequently with the stentless
      3f valve (Gen2). The valve is sewn at the base of the graft sinuses, leaving
      residual proximal graft to sew separately to the left ventricular outflow tract.
      This allows for CBG size standardization and permits fabrication prior to bypass.
      We share our institutional experience and aim to show noninferiority of this
      technique, as well as discuss potential advantages. METHODS: The first 75
      patients to receive each generation of CBG were identified and assessed
      retrospectively. Overall survival was assessed as our primary outcome. Various
      secondary outcomes were also analyzed, including operative times and short-term
      outcomes. RESULTS: Operative times were shorter for Gen2, with cardiopulmonary
      bypass times that were significantly reduced (126.3 +/- 5.2 minutes vs. 157.6 +/-
      5.8 minutes for Gen1, p = 0.001) and aortic cross-clamp times that trended lower
      (98.2 +/- 4.2 minutes vs. 107.7 +/- 3.8 minutes for Gen1, p = 0.095). There were
      no postoperative myocardial infarctions (MIs) or aortic insufficiency graded 2+
      or greater in either group. There was only one stroke in a Gen1 patient who
      recovered fully. Kaplan-Meier survival analysis showed a strong trend toward
      improved survival among Gen2 patients (p = 0.0566). CONCLUSIONS: Our experience
      with Gen2 CBG showed decreased operative times and a trend toward improved
      survival, though further patient follow-up and larger sample sizes in prospective
      studies are necessary. Further research with this CBG and additional improvements
      are warranted.

PMID- 24118070
TI  - Covariate effects and population pharmacokinetics of lamivudine in HIV-infected
      children.
AB  - AIM: Lamivudine is used as first line therapy in HIV-infected children. Yet, like
      many other paediatric drugs, its dose rationale has been based on limited
      clinical data, without thorough understanding of the effects of growth on drug
      disposition. Here we use lamivudine to show how a comprehensive population
      pharmacokinetic model can account for the influence of demographic covariates on
      exposure (i.e. AUC and Cmax ). METHODS: Data from three paediatric trials were
      used to describe the pharmacokinetics across the overall population. Modelling
      was based on a non-linear mixed effects approach. A stepwise procedure was used
      for covariate model building. RESULTS: A one compartment model with first order
      elimination best described the pharmacokinetics of lamivudine in children. The
      effect of weight on clearance (CL) and volume of distribution (V) was
      characterized by an exponential function, with exponents of 0.705 and 0.635,
      respectively. For a child with median body weight (17.6 kg), CL and V were 16.5
      (95% CI 15.2, 17.7) l h-1 and 46.0 (95% CI 42.4, 49.5) l, respectively. There
      were no differences between formulations (tablet and solution). The predicted
      AUC(0,12 h) after twice daily doses of 4 mg kg-1 ranged from 4.44 mg l-1  h for
      children <14 kg to 7.25 mg l-1  h for children >30 kg. CONCLUSIONS: The use of
      meta-analysis is critical to identify the correct covariate-parameter
      relationships, which must be assessed before a model is applied for predictive
      purposes (e.g. defining dosing recommendations for children). In contrast to
      prior modelling efforts, we show that the covariate distribution in the target
      population must be considered.

PMID- 24118074
TI  - Complexes of Chlorin e6 with Pluronics and Polyvinylpyrrolidone: Structure and
      Photodynamic Activity in Cell Culture.
AB  - Polymeric carriers are extensively used in photodynamic therapy (PDT) for
      increase of efficacy of photosensitizers. Here, we report the influence of nine
      Pluronic copolymers on phototoxicity of chlorin e6 (Ce6), in particular 5- to 7
      fold rise in the phototoxicity caused by hydrophilic Pluronics F127, F108, F68
      and F87 and practically no influence on Ce6 of more hydrophobic polymers. The
      revealed value of 0.2 mg mL(-1) of Pluronic F127 concentration sufficient for
      half-of-maximal increase of Ce6 photodynamic activity proved to be close to 0.16
      mg mL(-1) inherent in well-documented carrier poly(N-vinylpyrrolidone) (PVP). The
      dissociation constants of Ce6 complexes with Pluronic F127 and PVP that were
      estimated from UV spectra were 0.252 and 0.036 mg mL(-1) , respectively,
      indicating higher stability of Ce6 complex with PVP. According to the results of
      (1) H-NMR studies of Ce6 complexes, the porphyrin interacts not only with
      hydrophobic regions but also with hydrophilic sides of both polymers.

PMID- 24118075
TI  - Plasmid-mediated fitness advantage of Acinetobacter baylyi in sulfadiazine
      polluted soil.
AB  - LowGC-type plasmids conferring resistance to sulfonamides have been frequently
      isolated from manure and manured soil. However, knowledge on the dynamics of
      plasmid-carrying populations in soil and their response to the presence of
      sulfonamides is scarce. Here, we investigated effects of the sulfonamide
      resistance conferring plasmid pHHV216 on the fitness of Acinetobacter baylyi
      BD413 in soil after application of manure with or without the sulfonamide
      antibiotic sulfadiazine (SDZ). The persistence of A. baylyi BD413 pHHV216 in
      competition to its plasmid-free variant was followed in soil microcosms. CFU
      counts showed a decrease in A. baylyi BD413 in manured soils over the
      experimental period of 32 days by about 0.5 log units. The proportion of the
      plasmid-carrying populations decreased from 50 to < 40% in the absence of SDZ,
      while the proportion of plasmid-carrying BD413 increased from 50 to about 65%
      with SDZ added. The data suggest that SDZ introduced via manure into soil was
      bioaccessible, providing a fitness advantage for the plasmid-carrying population
      of BD413 in soil, while the plasmid conferred a fitness disadvantage when
      selective pressure by SDZ was absent. In future, this method may be used as a
      tool for the assessment of bioavailability of antibiotics in soil.

PMID- 24118076
TI  - The effect of maturation on adaptations to strength training and detraining in 11
      15-year-olds.
AB  - To investigate how maturity status modifies the effects of strength training and
      detraining on performance, we subjected 33 young men to 8 weeks of strength
      training twice per week followed by 8 weeks without training. Changes in
      performance tests were analyzed in three maturity groups based on years from/to
      age of predicted peak height velocity (PHV): pre-PHV (-1.7 +/- 0.4 years; n =
      10), mid-PHV (-0.2 +/- 0.4 years; n = 11), and post-PHV (1.0 +/- 0.4 years; n =
      12). Mean training effects on one repetition maximum strength (3.6-10.0%),
      maximum explosive power (11-20%), jump length (6.5-7.4%), and sprint times (-2.1%
      to -4.7%) ranged from small to large, with generally greater changes in mid- and
      post-PHV groups. Changes in force-velocity relationships reflected generally
      greater increases in strength at faster velocities. In the detraining period, the
      pre-PHV group showed greatest loss of strength and power, the post-PHV group
      showed some loss of sprint performance, but all groups maintained or improved
      jump length. Strength training was thus generally less effective before the
      growth spurt. Maintenance programs are needed for most aspects of explosive
      performance following strength training before the growth spurt and for sprint
      speed after the growth spurt.

PMID- 24118077
TI  - Efficacy of medical treatment in Cushing's disease: a systematic review.
AB  - OBJECTIVE: Reported rates of response to medical therapies used in Cushing's
      disease (CD) vary widely. The aim of this review is to analyse systematically the
      efficacy of medical therapies for CD and to assess the strength of the supporting
      evidence. METHODS: Systematic PubMed searches identified studies of medical
      treatment in CD. The GRADE criteria were imposed to assess the strength of
      evidence supporting each medication. RESULTS: Fifteen studies were included. Ten
      studies specifically reported response rates for patients with CD. Pasireotide
      was the only treatment to be assessed in a randomized trial and was supported by
      a 'moderate' level of evidence. Response rates with pasireotide from three
      prospective studies were 17-29%. The remaining medications were supported by a
      'low' or 'very low' level of evidence. The highest response rates were reported
      in small retrospective studies of metyrapone (75%, one study) and mitotane (72%,
      one study). Response rates were 25-50% for cabergoline (four studies) and 45% for
      ketoconazole (one study). Among studies that included patients with other forms
      of Cushing's syndrome, response rates were 53-88% for ketoconazole (three
      studies), 70% for mitotane (one study), 57% for metyrapone (one study) and 38-60%
      for mifepristone. Again, all of these medications are supported by a 'low' level
      of evidence. CONCLUSIONS: There is a paucity of high-quality studies of medical
      therapy in CD, with only one medication achieving a 'moderate' level of evidence.
      Caution should be employed when comparing efficacy rates owing to the variability
      in study design and quality.

PMID- 24118078
TI  - Aortopulmonary fistula presenting with right ventricular dysfunction following
      blunt chest trauma.

PMID- 24118079
TI  - Distinguishing the impact of dexlansoprazole on heartburn vs. regurgitation in
      patients with gastro-oesophageal reflux disease.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) is characterised by
      symptomatic heartburn and regurgitation. Treatment with proton pump inhibitors
      (PPI) effectively decreases heartburn symptoms, but their effects on symptomatic
      regurgitation are less clear. AIM: To determine the impact of PPI therapy on
      heartburn and regurgitation severity in patients with either non-erosive GERD
      (NERD) or erosive oesophagitis (EE). METHODS: Endoscopically-confirmed NERD
      patients received dexlansoprazole 30 or 60 mg or placebo in a randomised,
      blinded, 4-week study. Endoscopically-confirmed EE patients received
      dexlansoprazole 60 mg or lansoprazole 30 mg in two 8-week, randomised, blinded
      healing studies. The Patient Assessment of Upper Gastrointestinal Symptom
      Severity questionnaire, which includes a heartburn/regurgitation subscale, was
      administered to assess symptom severity at baseline, and at weeks 2 and 4 of the
      NERD study and at weeks 4 and 8 during the EE trials. We defined separate
      subscales for heartburn and regurgitation for this post-hoc analysis. Among
      patients with both symptoms at baseline, improvements in individual heartburn and
      regurgitation subscales along with the original combined heartburn/regurgitation
      subscale were determined. RESULTS: In the NERD and EE studies, 661 and 1909
      patients, respectively, had both heartburn and regurgitation at baseline. NERD
      patients receiving dexlansoprazole 30 and 60 mg experienced significantly greater
      improvements in symptom severity for both heartburn and regurgitation compared
      with placebo. EE patients receiving dexlansoprazole 60 mg had significantly
      greater improvements in heartburn/regurgitation and heartburn-only subscales at
      week 4 compared with those receiving lansoprazole. CONCLUSIONS: Dexlansoprazole
      appears to be effective in improving both heartburn and regurgitation, and this
      improvement is maintained for the duration of treatment.

PMID- 24118080
TI  - Stromal expression of neutrophil gelatinase-associated lipocalin correlates with
      poor differentiation and adverse prognosis in oral squamous cell carcinoma.
AB  - AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the
      lipocalin superfamily. Although its overexpression in various cancers has been
      reported, little is known about its expression and clinical significance in oral
      squamous cell carcinoma (OSCC). This study aimed to elucidate the clinical
      significance of NGAL in OSCC. METHODS AND RESULTS: We investigated NGAL
      expression immunohistochemically in tumour cells and stromal cells in 96 OSCC
      tissues. NGAL expression in tumour cells correlated significantly with
      histological tumour cell differentiation, as shown by its specific distribution
      in the horn pearl-forming keratinized tumour cells, but not with other major
      clinicopathological parameters. We found NGAL(+) cells in the stroma that were
      predominantly myeloperoxidase-positive neutrophils. The number of such NGAL
      expressing stromal cells was associated significantly with poor differentiation
      and reduced overall survival in OSCC. The prognostic value of stromal NGAL
      expression was significant in a univariate analysis, while only a trend was found
      in multivariate analyses. CONCLUSIONS: This study is the first to show the
      clinical significance of stromal NGAL expression, which may be an indicator of
      poor prognosis and more aggressive histological grade in OSCC. Our data suggest
      that NGAL expression in tumour cells and expression in stroma are associated in
      different ways with OSCC differentiation.

PMID- 24118081
TI  - Influences of social network sites on the occupational performance of adolescents
      in a secondary school in Cape Town, South Africa: a phenomenological study.
AB  - BACKGROUND/AIM: The habit of using social networking sites among adolescents has
      grown exponentially; there is little accompanying research to understand the
      influences on adolescents' occupational performance with this technology. The
      majority of adolescents are engaging in social network as part of their daily
      routines. Occupational performance is the act of doing and accomplishing a
      selected occupation that results from the dynamic transaction among the person,
      the environment and the occupation components. This study aimed to explore the
      influences of social networking on occupational performance of adolescents in a
      high school in Western Cape Province, South Africa. METHODS: A phenomenological
      approach was used. Adolescents aged 13-17 years in a high school were purposively
      recruited for the study. Semi-structured interviews were conducted with four
      participants (two adolescents and two teachers) and two focus groups were
      undertaken with adolescents, analysed using thematic analysis. RESULTS: Four
      major themes emerged: 'It's a good way to keep in touch', 'It's part of me and
      it's not a bad thing', 'There is a time and place for it' and 'There's an urgency
      to be on the phone'. CONCLUSIONS: This study highlighted that social networking
      sites play a major role in the social life of adolescents, though it can result
      in occupational imbalance on their occupational performance. Furthermore, this
      study contributes to the knowledge of occupational therapists who work with
      adolescents in communities and health promoting school settings. Thus,
      collaboration between teachers, parents and occupational therapists can help to
      develop adolescents' time management and learning skills.

PMID- 24118082
TI  - Dual treatment for obscure gastrointestinal bleeding from hepaticojejunostomy
      using double balloon enteroscopy technique.

PMID- 24118083
TI  - Autonomy and choice in palliative care: time for a new model?
AB  - AIMS: This paper will examine understandings of autonomy and choice in relation
      to palliative and end-of-life care and identify implications for nursing
      practice. BACKGROUND: Autonomy in relation to patient-centred care and advocacy
      has been identified as a key component of palliative and end-of-life care
      provision internationally. Understandings of autonomy have emerged in an
      individualised framework, which may be inadequate in supporting palliative and
      end-of-life care. DESIGN: A critical discussion paper. DATA SOURCES: Seminal
      texts provide a backdrop to how autonomy is understood in the context of
      palliative care. An overview of literature from 2001 is examined to explore how
      autonomy and choice are presented in clinical practice. IMPLICATIONS FOR NURSING:
      A model of autonomy based on a 'decision ecology' model may be more applicable to
      palliative and end-of-life care. Decision ecology aims to situate the individual
      in a wider social context and acknowledges the relational dimensions involved in
      supporting choice and autonomy. Such a model recognizes autonomy around wider
      care decisions but may also highlight the everyday personal aspects of care,
      which can mean so much to an individual in terms of personal empowerment and
      dignity. CONCLUSION: A 'decision ecology' model that acknowledges the wider
      social context, individual narratives and emphasises trust between professionals
      and patients may support decision-making at end of life. Such a model must
      support autonomy not just at the level of wider decisions around care choice but
      also at the level of everyday care.

PMID- 24118084
TI  - Nutritional interventions to prevent and rear low-birthweight piglets.
AB  - Selection for hyperprolific sows, as a means of increasing litter size and
      profit, has resulted in an increased number of low-birthweight (LBW) piglets.
      These LBW piglets might suffer from increased morbidity and mortality during the
      early neonatal period. In addition, they show reduced growth performance, meat
      and carcass quality, which leads to an important economic loss for the farmer in
      the post-natal period. Therefore, nutritional interventions can be undertaken to
      prevent and rear LBW piglets. In the first part of this review, the preventive
      strategies at the sow level will be discussed. Approaches in preventing LBW
      piglets are to optimize the intrauterine environment via supplementing the sow
      during gestation. In the second part of this review, the interventions at the
      piglet level will be described. To increase the survival and growth rates of LBW
      piglets, one must focus on ensuring adequate colostrum and milk intake.
      Interventions include supplementing piglets, split nursing, split weaning and
      cross-fostering. Additional interventions increasing the probability of optimal
      post-natal food intake will be discussed. 

PMID- 24118086
TI  - Placental abruption as a significant risk factor for long-term cardiovascular
      mortality in a follow-up period of more than a decade.
AB  - BACKGROUND: To investigate the risk for subsequent cardiovascular events in women
      having placental abruption during a follow-up period of more than 10 years.
      METHODS: A population-based study of the incidence of cardiovascular events in
      women who had placental abruption with women without placental abruption during
      1988-99 and with follow-up until 2010. Associations between placental abruption
      and maternal long-term cardiovascular morbidity and mortality were investigated.
      Kaplan-Meier survival curves and multivariable Cox regression were used to
      estimate cumulative incidence of cardiovascular mortality. RESULTS: During the
      study period, there were 47 585 deliveries meeting the inclusion criteria; of
      these, 653 occurred in patients with placental abruption. No significant
      association was noted between placental abruption and subsequent long-term
      hospitalisations because of cardiovascular causes. However, placental abruption
      was associated with long-term cardiovascular mortality [odds ratio (OR) = 6.6;
      95% confidence interval (CI) 2.3, 18.3]. The cardiovascular case fatality rate
      for the placental abruption group was 13.0% vs. 2.5% in the comparison group (P <
      0.001). Patients with a history of placental abruption had a significantly higher
      risk for cardiovascular mortality during the follow-up period (Log-rank test P =
      0.017). Using Cox multivariable regression models, placental abruption remained
      an independent risk factor for long-term maternal cardiovascular mortality
      [adjusted hazard ratio (HR) = 4.3; 95% CI 1.1, 18.6). CONCLUSION: Placental
      abruption is a significant risk factor for long-term cardiovascular mortality in
      a follow-up period of more than a decade.

PMID- 24118087
TI  - Influence of gag reflex on dental attendance, dental anxiety, self-reported
      temporomandibular disorders and prosthetic restorations.
AB  - To assess the influence of gag reflex severity, assessed according to the short
      form of the patient part of Gagging Problem Assessment Questionnaire (GPA-pa SF),
      on the dental attendance, dental anxiety, self-reported temporomandibular
      disorder (TMD) symptoms and presence of prosthetic restorations among patients
      requiring prosthodontic treatment in Turkey. A total of 505 patients (305 women;
      mean age: 46.35 years, SD: 28.2 years) undergoing dental examination were
      administered a questionnaire containing questions regarding their age, gender,
      education level, dental attendance, TMD symptoms (limitation in jaw opening,
      muscle pain, pain/sounds in the temporomandibular jaw), the Turkish version of
      the Modified Dental Anxiety Scale (MDAS) and the GPA-pa SF. Subsequently, any
      prosthetic restoration was recorded by a dentist. Descriptive statistics, one-way
      analysis of variance (anova) and the chi-square test were used for statistical
      analysis. Differences were found between GPA-pa SF scores 0, 1 and 2 for
      education level (P = 0.001), MDAS scores (P = 0.003), self-reported TMD (P =
      0.000) and prosthesis wear (P = 0.000), but not for attendance patterns (P =
      0.826). Patients with gag reflex had lower education levels, higher levels of
      dental anxiety, more self-reported TMD symptoms and fewer fixed or removable
      prosthetic restorations than patients without gag reflex. Gag reflex has impacts
      on dental anxiety, self-reported TMD and prosthetic restorations, but not on
      dental attendance patterns, according to the results of the GPA-pa SF. 

PMID- 24118085
TI  - The bacterial chromosome: architecture and action of bacterial SMC and SMC-like
      complexes.
AB  - Structural Maintenance of Chromosomes (SMC) protein complexes are found in all
      three domains of life. They are characterized by a distinctive and conserved
      architecture in which a globular ATPase 'head' domain is formed by the N- and C
      terminal regions of the SMC protein coming together, with a c. 50-nm-long
      antiparallel coiled-coil separating the head from a dimerization 'hinge'.
      Dimerization gives both V- and O-shaped SMC dimers. The distinctive architecture
      points to a conserved biochemical mechanism of action. However, the details of
      this mechanism are incomplete, and the precise ways in which this mechanism leads
      to the biological functions of these complexes in chromosome organization and
      processing remain unclear. In this review, we introduce the properties of
      bacterial SMC complexes, compare them with eukaryotic complexes and discuss how
      their likely biochemical action relates to their roles in chromosome organization
      and segregation. 

PMID- 24118088
TI  - Assessing play-based activities, child talk, and single session outcome in family
      therapy with young children.
AB  - This exploratory, observational study was designed to reveal descriptive
      information regarding therapists' actual practices with preschool- and school
      aged children in a single session of family therapy and to investigate change
      mechanisms in family play therapy that have been proposed to make this approach
      effective. A purposive sample of 30 families receiving family therapy was
      recruited and video-taped during a family session where at least one child
      between the ages of 4 and 12 was present. Following the session, the therapist
      and parent(s) completed questionnaires while one of the children (aged 4-12) was
      interviewed. Session recordings were coded, minute-by-minute, for participant
      talk time, visual aids or props used, and therapy technique type (e.g., play
      based/activity vs. talk-only techniques). Hierarchical regression and canonical
      correlational analyses revealed evidence supporting the theory that play-based
      techniques promote young children's participation, enhance the quality of the
      child-therapist relationship, and build positive emotional experiences in family
      therapy. 

PMID- 24118089
TI  - White matter microstructure is influenced by extremely preterm birth and neonatal
      respiratory factors.
AB  - AIM: The aim of this study was to investigate whether prematurity per se or
      perinatal risk factors explain altered brain structure after preterm birth, in
      extremely preterm (EPT) infants without focal brain lesions. METHODS: A
      population-based cohort of 58 EPT infants [gestational age (GA) <27 + 0 weeks]
      was examined with diffusion magnetic resonance imaging at term-equivalent age and
      compared with 14 term-born controls. Associations of diffusion measures with
      prematurity and neonatal risk factors were explored. Data were analysed with
      tract-based spatial statistics (TBSS) for whole-brain analysis and region-of
      interest (ROI) analysis. RESULTS: Whole-brain analyses showed lower fractional
      anisotropy (FA) and higher mean diffusivity (MD) in several white matter (WM)
      tracts in the preterms, which was essentially confirmed by ROI analyses. Within
      the preterm GA range (23 + 0 to 26 + 6 weeks), GA at birth was not significantly
      associated with diffusion measures. Bronchopulmonary dysplasia predicted lower FA
      in the corpus callosum and right inferior longitudinal fasciculus; mechanical
      ventilation >2 days was predictive of higher MD in the right external capsule.
      CONCLUSION: White matter microstructure is influenced by preterm birth and by
      neonatal respiratory factors, whereas the degree of prematurity within the EPT
      range appears to be of less importance.

PMID- 24118090
TI  - Hemodialysis for the treatment of severe accidental hypothermia.
AB  - Severe hypothermia is defined as a core body temperature <28 degrees C and is
      associated with in-hospital mortality rates of 50% or higher. Delays in rewarming
      and slower rates of rewarming are the most important prognostic factors
      associated with increased mortality. Arrhythmias are the most common cause of
      mortality in patients with severe accidental hypothermia. Electrolyte
      abnormalities such as hyperkalemia and hypocalcemia that may worsen when patients
      are rewarmed contribute to the risk of arrhythmias. Cardiopulmonary bypass (CBP)
      is considered the treatment of choice for active internal rewarming of patients
      with severe hypothermia, but it is not always available and is time consuming to
      initiate. We describe a case where hemodialysis (HD) was used to treat accidental
      hypothermia in a patient with an initial temperature of 23.5 degrees C. Average
      rewarming rates of 1.5 degrees C/hour were achieved. The advantages of HD when
      compared with CBP are that it is (1) more widely and readily available, (2) less
      invasive, (3) less expensive, and (4) can correct associated acidosis and
      electrolyte abnormalities commonly seen in patients with severe hypothermia. 

PMID- 24118091
TI  - Combined therapies versus monotherapies for the first variceal bleeding in
      patients with high-risk varices: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND AIM: The effect of combined therapies (among non-selected beta
      blockers [NSBB], endoscopic therapy, and other treatments) on the first variceal
      bleeding has been evaluated in several randomized controlled trials previously,
      and the results were controversial. We performed this meta-analysis to assess the
      effect of combined therapies in patients with high-risk varices without previous
      variceal bleeding. METHODS: The Cochrane Library, The Cochrane Hepato-Biliary
      Group Controlled Trials Register, MEDLINE, and EMBASE were searched for eligible
      trials. Manual searches were also performed for additional studies. Upper
      gastrointestinal bleeding, variceal bleeding, mortality, and adverse events were
      evaluated as end-points by meta-analysis. RESULTS: Twelve randomized controlled
      trials with 1571 patients were included. Compared with the NSBB (propranolol or
      nadolol) or endoscopic therapy alone, all of the combined therapies did not
      demonstrate significant improvements in variceal bleeding, total upper
      gastrointestinal bleeding, and mortality. Only the combinations of isosorbide
      mononitrate or spironolactone with NSBB tended to decrease the risk of variceal
      bleeding when compared with the use of NSBB alone (isosorbide-mononitrate plus
      NSBB vs NSBB: odds ratio = 0.67, 95% confidence interval 0.40-1.13, P = 0.13;
      spironolactone plus NSBB vs NSBB: odds ratio = 0.41, 95% confidence interval 0.10
      1.69, P = 0.22). Adverse events were more frequently observed in the combined
      therapy groups. CONCLUSIONS: Based on the available evidences, no combined
      therapy can be recommended as the first-line treatment for the primary prevention
      of variceal bleeding currently. Further studies with large sample sizes and long
      term follow up are warranted.

PMID- 24118092
TI  - Are obesity and overweight associated with gingivitis occurrence in Brazilian
      schoolchildren?
AB  - AIM: This cross-sectional study aimed to assess the relationship between weight
      status and gingival inflammation in Brazilian schoolchildren aged 8- to 12-year
      old, when controlling for potential confounders. METHODS: Overall, 1211 children
      aged 8- to 12-year old from public and private schools in Southern Brazil were
      selected by a two-stage cluster method. Questionnaires were used to assess socio
      demographic data and oral hygiene habits. Oral examination evaluated presence of
      plaque and gingival bleeding. Anthropometric measures were collected to obtain
      body mass index. Multivariate Poisson regression was used for data analysis
      (Prevalence Ratio/95% Confidence Interval). RESULTS: Prevalence of gingivitis was
      44.0%. Mean and median values of gingival bleeding sites were 3.10 and 2.0
      respectively. Obese/overweight children totalized 34.6%. In multivariate adjusted
      analysis, sex (PR 0.86; 95%CI 0.75;0.98), maternal schooling (PR 1.09; 95% CI
      1.01;1.18), plaque (PR 1.37; 95% CI 1.26;1.50), dental caries experience (PR
      1.16; 95% CI 1.01;1.36) and bleeding during tooth brushing (PR 1.27; 95% CI
      1.11;1.48) were associated with the outcome. In the sex-stratified analysis,
      overweight/obese boys presented a greater risk for gingivitis (PR 1.22 95% CI
      1.01;1.48). CONCLUSIONS: Gingivitis was not associated with obesity/overweight in
      the total sample. Gender differences seem to influence the relationship between
      gingivitis and obesity/overweight; a stronger association was noted among boys
      than girls.

PMID- 24118093
TI  - Psychological factor, metacognition, is associated with the advantage of suturing
      techniques acquired on a virtual reality simulator of robot-assisted surgery.

PMID- 24118094
TI  - Transporter-mediated replacement of extracellular glutamate for GABA in the
      developing murine neocortex.
AB  - During early development, cortical neurons migrate from their places of origin to
      their final destinations where they differentiate and establish synaptic
      connections. During corticogenesis, radially migrating cells move from deeper
      zone to the marginal zone, but they do not invade the latter. This "stop"
      function of the marginal zone is mediated by a number of factors, including
      glutamate and gamma-aminobutyric acid (GABA), two main neurotransmitters in the
      central nervous system. In the marginal zone, GABA has been shown to be released
      via GABA transporters (GAT)-2/3, whereas glutamate transporters (EAATs) operate
      in the uptake mode. In this study, GABAergic postsynaptic currents (GPSCs) were
      recorded from Cajal-Retzius cells in the marginal zone of murine neonatal
      neocortex using a whole-cell patch-clamp technique. Minimal electrical
      stimulation was applied to elicit evoked GPSCs using a paired-pulse protocol.
      EAAT blockade with dl-threo-b-benzyloxyaspartic acid (dl-TBOA), a specific non
      transportable EAAT antagonist, abolishes constitutive GAT-2/3-mediated GABA
      release. In contrast to dl-TBOA, d-aspartate, an EAAT substrate, fails to block
      GAT-2/3-mediated GABA release. SNAP-5114, a specific GAT-2/3 antagonist, induced
      an elevation of intracellular sodium concentration ([Na(+) ]i ) under resting
      conditions and in the presence of d-aspartate, indicating that GAT-2/3 operates
      in reverse mode. In the presence of dl-TBOA, however, SNAP-5114 elicited a [Na(+)
      ]i decrease, demonstrating that GAT-2/3 operates in uptake mode. We conclude that
      EAATs via intracellular Na(+) signaling and/or cell depolarization can govern the
      strength/direction of GAT-mediated GABA transport. 

PMID- 24118095
TI  - Adverse drug reactions during ceftriaxone treatment can cause severe hemolysis.

PMID- 24118096
TI  - Methionine sulphoxide reductases revisited: free methionine as a primary target
      of H2O2stress in auxotrophic fission yeast.
AB  - Amino acid methionine can suffer reversible oxidation to sulphoxide and further
      irreversible over-oxidation to methionine sulphone. As part of the cellular
      antioxidant scavenging activities are the methionine sulphoxide reductases
      (Msrs), with a reported role in methionine sulphoxide reduction, both free and in
      proteins. Three families of Msrs have been described, but the fission yeast
      genome only includes one representative for two of these families: MsrA/Mxr1 and
      MsrB/Mxr2. We have investigated their role in methionine reduction and H2 O2
      sensitivity. We show here that MsrA/Mxr1 is able to reduce free oxidized
      methionine. Cells lacking each one of the genes are not significantly sensitive
      to different types of oxidative stresses, neither display altered life span.
      However, only when deletion of msrA/mxr1 is combined with deletion of met6, which
      confers methionine auxotrophy, the survival upon H2 O2 stress decreases by 100
      fold. In fact, cells lacking only Met6, and which therefore require addition of
      methionine to the growth media, are extremely sensitive to H2 O2 stress. These
      and other evidences suggest that oxidation of free methionine is a primary target
      of peroxide toxicity in cells devoid of methionine biosynthetic capacity, and
      that an important role of Msrs is to recycle this oxidized free amino acid. 

PMID- 24118097
TI  - High- and moderate-intensity aerobic exercise and excess post-exercise oxygen
      consumption in men with metabolic syndrome.
AB  - Physical activity is central in prevention and treatment of metabolic syndrome.
      High-intensity aerobic exercise can induce larger energy expenditure per unit of
      time compared with moderate-intensity exercise. Furthermore, it may induce larger
      energy expenditure at post-exercise recovery. The aim of this study is to compare
      the excess post-exercise oxygen consumption (EPOC) in three different aerobic
      exercise sessions in men with metabolic syndrome. Seven men (age: 56.7 +/- 10.8)
      with metabolic syndrome participated in this crossover study. The sessions
      consisted of one aerobic interval (1-AIT), four aerobic intervals (4-AIT), and 47
      min continuous moderate exercise (CME) on separate days, with at least 48 h
      between each test day. Resting metabolic rate (RMR) was measured pre-exercise and
      used as baseline value. EPOC was measured until baseline metabolic rate was re
      established. An increase in O2 uptake lasting for 70.4 +/- 24.8 min (4-AIT), 35.9
      +/- 17.3 min (1-AIT), and 45.6 +/- 17.3 min (CME) was observed. EPOC were 2.9 +/-
      1.7 L O2 (4-AIT), 1.3 +/-  .1 L O2 (1-AIT), and 1.4 +/- 1.1 L O2 (CME). There
      were significant differences (P < 0.001) between 4-AIT, CME, and 1-AIT. Total
      EPOC was highest after 4-AIT. These data suggest that exercise intensity has a
      significant positive effect on EPOC in men with metabolic syndrome.

PMID- 24118099
TI  - Risk factors for acute kidney injury in patients undergoing same admission
      coronary angiography and valve replacement.
AB  - BACKGROUND: We investigated risk factors for acute kidney injury (AKI) in
      patients undergoing same admission coronary angiography (CAG) and valve
      replacement. METHODS: Among 283 consecutive patients undergoing valve surgery
      between October 2010 and July 2012, 71 patients with same admission preoperative
      CAG were included in the study. Predictors of AKI were identified with a
      univariable model; then, logistic regression analysis was performed with the
      variables with p < 0.1 in univariable analysis and other known risk factors of
      AKI. RESULTS: Twenty-two (31.0%) patients developed AKI. Univariate analysis
      revealed that diabetes mellitus (p = 0.097), cerebrovascular disease (p = 0.03),
      atrial fibrillation (p = 0.097), one-stage procedure (p = 0.05), and concomitant
      tricuspid valvular replacement/repair (p = 0.033) were risk factors. Multivariate
      logistic regression analysis showed that diabetes mellitus (odds ratio [OR]
      10.361, 95% CI 1.345-79.828, p = 0.025) and cerebrovascular disease (OR 26.070,
      95% CI 1.695-400.939, p = 0.019) are risk factors for AKI in patients 50 years or
      older undergoing same admission CAG and valve replacement. One-stage procedure
      was not associated with a higher incidence of AKI. CONCLUSION: Diabetes mellitus
      and cerebrovascular disease are risk factors for AKI. Same admission CAG and
      valve replacement should be performed with caution in this group of patients.

PMID- 24118098
TI  - Clinical implementation of pharmacogenetics in kidney transplantation:
      calcineurin inhibitors in the starting blocks.
AB  - Pharmacogenetics has generated many expectations for its potential to
      individualize therapy proactively and improve medical care. However, despite the
      huge amount of reported genetic associations with either pharmacokinetics or
      pharmacodynamics of drugs, the translation into patient care is still slow. In
      fact, strong evidence for a substantial clinical benefit of pharmacogenetic
      testing is still limited, with a few exceptions. In kidney transplantation,
      established pharmacogenetic discoveries are being investigated for application in
      the clinic to improve efficacy and to limit toxicity associated with the use of
      immunosuppressive drugs, especially the frequently used calcineurin inhibitors
      (CNIs) tacrolimus and ciclosporin. The purpose of the present review is to
      picture the current status of CNI pharmacogenetics and to discuss the most
      promising leads that have been followed so far. 

PMID- 24118100
TI  - Loss of special AT-rich sequence-binding protein 1 (SATB1) predicts poor survival
      in patients with colorectal cancer.
AB  - AIM: Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific
      matrix attachment region binding protein, functioning as a global genome
      organizer. This study aims to investigate the expression pattern and the
      prognostic value of SATB1 in colorectal cancer. METHODS AND RESULTS:
      Prospectively collected data were obtained and tissue microarrays were
      constructed from a cohort of 352 patients. SATB1 protein expression was evaluated
      by immunohistochemistry and scored by two independent investigators. SATB1
      expression was predominantly nuclear in both normal and cancer tissues. Loss of
      SATB1 nuclear expression was seen in 22% of colorectal cancers compared to 1.5%
      of adjacent normal colorectal tissue, and was associated with worse overall
      survival (P = 0.02) independent of age and stage of disease (HR 2.48 with 95% CI
      1.31-4.70). Loss of SATB1 expression was more evident in younger patients (P =
      0.03), tumours with mucinous or signet ring histology (P = 0.0001) and poor
      differentiation (P = 0.005). SATB1 expression was associated with a survival
      advantage in patients with Dukes C tumours who received adjuvant chemotherapy.
      CONCLUSION: Loss of SATB1 nuclear expression correlates with poor survival and a
      less favourable response to adjuvant chemotherapy in colorectal cancer. The value
      of SATB1 in individualized colorectal cancer therapy warrants further evaluation.

PMID- 24118101
TI  - Are patients with autoimmune thyroid disease and autoimmune gastritis at risk of
      gastric neuroendocrine neoplasms type 1?
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of autoimmune
      gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric
      neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid
      disease. DESIGN: Prospective observational study in a single institutional study.
      PATIENTS AND MEASUREMENTS: One hundred and twenty patients with autoimmune
      thyroid disease were consecutively recruited from the Endocrine Unit. Upper
      gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune
      thyroid disease and autoimmune gastritis were assessed at recruitment and
      annually thereafter in patients with a mean follow-up of 37.5 +/- 14.4 months.
      Autoimmune gastritis was defined by the presence of antiparietal cell antibodies
      (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin
      Alpha were also measured. RESULTS: One hundred and eleven patients had
      Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was
      identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease)
      patients all of whom had increased levels of gastrin and chromogranin Alpha;
      Helicobacter pylori infection was histologically identified in 15 of 40 (37.5%)
      patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed
      nodular and linear ECL-cell hyperplasia [7 of 40 (17.5%)]. Only increased gastrin
      (P = 0.03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed
      in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up.
      CONCLUSIONS: Concomitant autoimmune gastritis was found in 33.3% of patients with
      autoimmune thyroid disease, 17.5% of whom had ECL-cell hyperplasia that evolved
      to GNEN1 in one (2.5%). Larger studies with longer follow-up are needed to define
      the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell
      hyperplasia and potential implications.

PMID- 24118102
TI  - Review article: immunogenicity of anti-TNF biologics in IBD - the role of
      patient, product and prescriber factors.
AB  - BACKGROUND: Anti-drug antibodies (ADAs) to biologic therapies contribute to the
      loss of response and infusion reactions to anti-TNF drugs in patients with
      inflammatory bowel disease (IBD). The reasons behind this immunogenicity are
      complex, and have not been the focus of a dedicated review for prescribers. AIM:
      To provide an overview of the patient, product and prescriber factors, which have
      been associated with the immunogenicity of anti-TNF therapy, and draw conclusions
      for clinical practice. METHODS: Review of representative observational studies
      and clinical trials from the IBD and other literature, which report associations
      with ADA development, with a focus on infliximab and adalimumab. RESULTS: ADAs
      develop in 10-20% of patients receiving anti-TNF maintenance therapy, and these
      patients are three times more likely to lose response as ADA-negative patients.
      Patient genotype plays a role in ADA risk in a minority of patients, but age or
      disease type is not a major factor. Drug mishandling, such as agitation or freeze
      thaw cycles, can induce protein aggregates, which are known to be immunogenic.
      Prescription of maintenance therapy with concomitant immunomodulators, and
      achieving suitable trough drug levels, reduces the risk of ADAs in patients with
      IBD. CONCLUSIONS: Patients and prescribers can take several steps to reduce the
      risk of development of anti-drug antibodies to anti-TNF antibodies. Further
      research is required to determine if immunogenic factors identified in other
      situations apply to use of anti-TNFs in IBD.

PMID- 24118103
TI  - New technique to carry out endoscopic necrosectomy lavage using a pump.

PMID- 24118104
TI  - The association of maternal intrapartum subfebrile temperature and adverse
      obstetric and neonatal outcomes.
AB  - BACKGROUND: Subfebrile intrapartum maternal temperature is very common, yet there
      is sparse evidence regarding its causes or its effects on perinatal outcomes. We
      examined whether mild temperature elevation during labour is a risk marker for
      adverse obstetric and neonatal outcomes. METHODS: A retrospective cohort analysis
      including 42 601 term, singleton live-births in two medical centres between 2003
      and 2010 was performed. This study compared women who experienced a maximal
      intrapartum temperature of <=37 degrees C with women who experienced subfebrile
      intrapartum temperature (37.1-37.9 degrees C). Adjusted risks for adverse
      obstetric and neonatal outcomes were calculated by using multivariable logistic
      regression models. RESULTS: Compared with maternal temperature <= 37 degrees C,
      subfebrile temperature was associated with higher rates of primary caesarean
      deliveries {adjusted odds ratios [aOR] = 1.36 [95% confidence interval (CI) 1.25,
      1.49])} and assisted vaginal deliveries (aOR = 1.20 [95% CI 1.11, 1.30]), as well
      as with greater risks of early neonatal sepsis (aOR = 2.66 [95% CI 1.88, 3.77]),
      neonatal intensive care unit admissions (aOR = 1.40 [95% CI 1.08, 1.83]), and
      neonatal asphyxia or seizures (aOR = 3.18 [95% CI 1.51, 6.70]). Mildly elevated
      maternal intrapartum temperature (37.1-37.5 degrees C) was also associated with
      adverse outcomes. CONCLUSIONS: Maternal intrapartum subfebrile temperature may be
      an indicator of operative delivery and neonatal morbidity. Further research is
      needed to confirm these findings and to reveal underlying mechanisms.

PMID- 24118105
TI  - The NLRP3 inflammasome: role in airway inflammation.
AB  - Asthma is characterized by airway inflammation, airway hyperresponsiveness and
      airway remodelling. Uncontrolled airway inflammation or repeated asthma
      exacerbations can lead to airway remodelling, which cannot be reversed by current
      pharmacological treatment, and consequently lead to decline in lung function.
      Thus, it is critical to understand airway inflammation in asthma and infectious
      exacerbation. The inflammasome has emerged as playing a key role in innate
      immunity and inflammation. Upon ligand sensing, inflammasome components assemble
      and self-oligomerize, leading to caspase-1 activation and maturation of pro-IL
      1beta and pro-IL-18 into bioactive cytokines. These bioactive cytokines then play
      a pivotal role in the initiation and amplification of inflammatory processes. In
      addition to facilitating the proteolytic activation of IL-1beta and IL-18,
      inflammasomes also participate in cell death through caspase-1-mediated
      pyroptosis. In this review, we describe the structure and function of the
      inflammasome and provide an overview of our current understanding of role of the
      inflammasome in airway inflammation. We focus on nucleotide-binding domain and
      leucine-rich repeat protein 3 (NLRP3) inflammasome as it is the best
      characterized subtype shown expressed in airway and considered to play a key role
      in chronic airway diseases such as asthma. 

PMID- 24118106
TI  - Evaluation of a psychoeducational intervention for patients with advanced cancer
      who have cachexia and their lay carers (EPACaCC): study protocol.
AB  - AIM: To evaluate a psychoeducational intervention for patients with advanced
      cancer who have cachexia and their lay carers. BACKGROUND: Cachexia is a frequent
      and devastating syndrome of advanced cancer. It has an impact on patients
      biologically, psychologically and socially and has profound impact on their lay
      carers. Prior research has predominately focused on the biological components of
      cachexia and associated potential treatment modalities. At present, there is no
      standardized supportive healthcare intervention in current practice that targets
      the psychosocial impact of this syndrome. DESIGN: A pragmatic multicentre
      randomized controlled trial. METHODS: Patient/carer dyads (n = 200) will be
      recruited into a randomized controlled trial of a DVD intervention for cachexia
      management. The sample will be recruited from two urban hospices in the UK. The
      primary outcome measure will be the General Health Questionnaire-12. Additional
      questionnaires focusing on distress, readiness to give care and coping skills
      will be used as secondary outcome measures. In addition, lay carers in the
      intervention group will be asked to participate in semi-structured interviews
      following the death of their loved one. Both Office for Research Ethics Committee
      approval and local governance approval at both hospices have been obtained as of
      February 2013. DISCUSSION: This is the first time that a psychoeducational DVD
      has been tested in a randomized controlled trial in this population.
      Dissemination of findings will make a significant contribution to international
      knowledge and understanding in this area. Findings will inform education,
      practice and policy.

PMID- 24118107
TI  - Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and
      literature review.
AB  - Onychomycosis is a common superficial fungal infection, which usually caused by
      dermatophytes, yeast and non-dermatophytic moulds. Recently, we isolated a
      Rhodotorula minuta isolate from a 15-year-old immunocompetent girl student in
      Hangzhou (China) that was identified using microscopy, culture morphology,
      histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of
      the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests
      showed that this yeast isolate was susceptible to low concentrations of
      amphotericin B, itraconazole, voriconazole and 5-flvoriconaz but that it appeared
      to be dose-dependent susceptible to fluconazole(MIC = 16 MUg/ml). Furthermore,
      the effective result of therapy with itraconazole against R. minuta was
      consistent with that of susceptibility tests. 

PMID- 24118108
TI  - Peptide pheromone signaling in Streptococcus and Enterococcus.
AB  - Intercellular chemical signaling in bacteria, commonly referred to as quorum
      sensing (QS), relies on the production and detection of compounds known as
      pheromones to elicit coordinated responses among members of a community.
      Pheromones produced by Gram-positive bacteria are comprised of small peptides.
      Based on both peptide structure and sensory system architectures, Gram-positive
      bacterial signaling pathways may be classified into one of four groups with a
      defining hallmark: cyclical peptides of the Agr type, peptides that contain Gly
      Gly processing motifs, sensory systems of the RNPP family, or the recently
      characterized Rgg-like regulatory family. The recent discovery that Rgg family
      members respond to peptide pheromones increases substantially the number of
      species in which QS is likely a key regulatory component. These pathways control
      a variety of fundamental behaviors including conjugation, natural competence for
      transformation, biofilm development, and virulence factor regulation. Overlapping
      QS pathways found in multiple species and pathways that utilize conserved peptide
      pheromones provide opportunities for interspecies communication. Here we review
      pheromone signaling identified in the genera Enterococcus and Streptococcus,
      providing examples of all four types of pathways. 

PMID- 24118110
TI  - Meta-analysis: is sequential therapy superior to standard triple therapy for
      Helicobacter pylori infection in Asian adults?
AB  - BACKGROUND AND AIM: Although several meta-analyses suggested that sequential
      therapy (SQT) is superior to standard triple therapy (STT) for the eradication of
      Helicobacter pylori, these results were mainly based on the studies from Italy.
      The aim of this study was to assess the efficacy of 10-day SQT for H. pylori
      infection compared with STT in Asian adults. METHODS: We performed an electronic
      search of the Cochrane Library, Medline, and Embase up to April 21, 2013, with no
      language restrictions. Randomized controlled trials comparing 10-day SQT with STT
      for H. pylori eradication in Asian adults were included in this analysis. The
      primary outcome measures were the risk ratios (RRs) for successful eradication of
      H. pylori based on intention to treat comparing SQT with STT. The secondary
      outcome measures were the RRs for side effects. RESULTS: Seventeen randomized
      controlled trials with a total of 3419 participants (1591 for SQT and 1828 for
      STT) met the inclusion criteria. The eradication rate was 81.8% (95% CI: 78.9
      84.6) for SQT and 74.3% (95% CI: 69.6-78.8) for SST, respectively. The pooled RR
      was 1.10 (95% CI: 1.04-1.16, P = 0.0005), which demonstrated significant
      superiority of SQT over STT, and the number needed to treat was 14 (95% CI: 9
      29). There were no significant differences between SQT and STT in the risk of
      side effects (the pooled RR: 0.98, 95% CI: 0.87-1.10, P = 0.73). CONCLUSION: Ten
      day SQT appears to be superior to STT for H. pylori eradication in Asian adults.
      However, the pooled efficacy is lower than results from earlier European studies.

PMID- 24118109
TI  - Continuous flow left ventricular assist device implant significantly improves
      pulmonary hypertension, right ventricular contractility, and tricuspid valve
      competence.
AB  - BACKGROUND: Continuous flow left ventricular assist devices (CF LVAD) are being
      implanted with increasing frequency for end-stage heart failure. At the time of
      LVAD implant, a large proportion of patients have pulmonary hypertension, right
      ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction
      and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy,
      edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased
      cardiopulmonary bypass time and bicaval cannulation, which should be reserved for
      the time of orthotopic heart transplantation. We hypothesized that CF LVAD
      implant would improve pulmonary artery pressures, enhance RV function, and
      minimize TR, obviating need for surgical tricuspid repair. METHODS: One hundred
      fourteen continuous flow LVADs implanted from 2005 through 2011 at a single
      center, with medical management of functional TR, were retrospectively analyzed.
      Pulmonary artery pressures were measured immediately prior to and following LVAD
      implant. RV function and TR were graded according to standard echocardiographic
      criteria, prior to, immediately following, and long-term following LVAD. RESULTS:
      There was a significant improvement in post-VAD mean pulmonary arterial pressures
      (26.6 +/- 4.9 vs. 30.2 +/- 7.4 mmHg, p = 0.008) with equivalent loading pressures
      (CVP = 12.0 +/- 4.0 vs. 12.1 +/- 5.1 p = NS). RV function significantly improved,
      as noted by right ventricular stroke work index (7.04 +/- 2.60 vs. 6.05 +/- 2.54,
      p = 0.02). There was an immediate improvement in TR grade and RV function
      following LVAD implant, which was sustained long term. CONCLUSION: Continuous
      flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid
      regurgitation. TR may be managed nonoperatively during CF LVAD implant.

PMID- 24118111
TI  - Monophyly of Wolbachia pipientis genomes within Drosophila melanogaster:
      geographic structuring, titre variation and host effects across five populations.
AB  - Wolbachia pipientis is one of the most widely studied endosymbionts today, yet we
      know little about its short-term adaptation and evolution. Here, using a set of
      91 inbred Drosophila melanogaster lines from five populations, we explore
      patterns of diversity and recent evolution in the Wolbachia strain wMel. Within
      the D. melanogaster lines, we identify six major mitochondrial clades and four
      wMel clades. Concordant with past studies, the Wolbachia haplotypes contain an
      overall low level of nucleotide diversity, yet they still display geographic
      structuring. Using Bayesian analysis informed with demographic estimates of
      colonization times, we estimate that all extant D. melanogaster mitochondrial
      haplotypes coalesce to a Wolbachia-infected ancestor approximately 2200 years
      ago. Finally, we measure wMel titre within the infected flies and find that titre
      varies across populations, an effect attributable to host genetic factors. This
      demonstration of local phenotypic divergence suggests that intraspecific host
      genetic variation plays a key role in shaping this model symbiotic system. 

PMID- 24118112
TI  - Legume adaptation to sulfur deficiency revealed by comparing nutrient allocation
      and seed traits in Medicago truncatula.
AB  - Reductions in sulfur dioxide emissions and the use of sulfur-free mineral
      fertilizers are decreasing soil sulfur levels and threaten the adequate
      fertilization of most crops. To provide knowledge regarding legume adaptation to
      sulfur restriction, we subjected Medicago truncatula, a model legume species, to
      sulfur deficiency at various developmental stages, and compared the yield,
      nutrient allocation and seed traits. This comparative analysis revealed that
      sulfur deficiency at the mid-vegetative stage decreased yield and altered the
      allocation of nitrogen and carbon to seeds, leading to reduced levels of major
      oligosaccharides in mature seeds, whose germination was dramatically affected. In
      contrast, during the reproductive period, sulfur deficiency had little influence
      on yield and nutrient allocation, but the seeds germinated slowly and were
      characterized by low levels of a biotinylated protein, a putative indicator of
      germination vigor that has not been previously related to sulfur nutrition.
      Significantly, plants deprived of sulfur at an intermediary stage (flowering)
      adapted well by remobilizing nutrients from source organs to seeds, ensuring
      adequate quantities of carbon and nitrogen in seeds. This efficient
      remobilization of photosynthates may be explained by vacuolar sulfate efflux to
      maintain leaf metabolism throughout reproductive growth, as suggested by
      transcript and metabolite profiling. The seeds from these plants, deprived of
      sulfur at the floral transition, contained normal levels of major
      oligosaccharides but their germination was delayed, consistent with low levels of
      sucrose and the glycolytic enzymes required to restart seed metabolism during
      imbibition. Overall, our findings provide an integrative view of the legume
      response to sulfur deficiency. 

PMID- 24118113
TI  - The optimal morning:evening ratio in total dose of twice-daily biphasic insulin
      analogue in poorly controlled Type 2 diabetes: a 24-week multi-centre
      prospective, randomized controlled, open-labelled clinical study.
AB  - AIMS: Biphasic insulin analogues are widely used in patients with Type 2 diabetes
      mellitus suboptimally controlled on oral anti-diabetic drugs. Several topics in
      this area remain controversial, including how to divide the daily dose of
      biphasic insulin analogue. We aimed to determine the optimal dosing ratio of
      twice-daily biphasic insulin analogue and to compare the glycaemic efficacy among
      groups of patients using different initial dosing ratios of biphasic insulin
      analogue. METHODS: A total of 100 poorly controlled insulin-naive subjects with
      Type 2 diabetes [HbA1c >= 58 mmol/mol, (7.5%)] on oral anti-diabetic drugs were
      randomized into three groups according to initial morning:evening dosing ratio
      (group I, 50:50; group II, 55:45; group III, 60:40) of twice-daily biphasic
      insulin analogue (biphasic insulin aspart 70/30, biphasic insulin aspart 30). The
      primary outcome measure was the difference in pre-breakfast to pre-dinner dose
      ratio at the end of the study. RESULTS: Twice-daily biphasic insulin analogue
      showed a significant improvement in glycaemic control [HbA1c from 70 mmol/mol
      (8.6%) to 60 mmol/mol (7.6%)] after 24 weeks regardless of the initial dose ratio
      given. Despite the similar efficacy and safety profiles among three groups,
      morning dose was significantly increased (from 50:50 to 55:45-60:40) in group I
      after 24 weeks. However, there was no significant change in splitting ratio in
      groups II and III (with higher morning dose) over the 24-week treatment period.
      CONCLUSIONS: These results indicate that initiating twice-daily biphasic insulin
      analogue on regimens with a higher dose before breakfast than before dinner (i.e.
      ratio approximately 55:45 to 60:40) might be more appropriate in Korean subjects
      with Type 2 diabetes.

PMID- 24118114
TI  - Collagen plug vascular closure devices and reduced risk of bleeding with
      bivalirudin versus heparin plus abciximab in patients undergoing percutaneous
      coronary intervention for non st-segment elevation myocardial infarction.
AB  - INTRODUCTION: In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST
      elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of
      bleeding after percutaneous coronary intervention (PCI) compared with
      unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices
      (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of
      bivalirudin. This analysis examined whether there exists an interaction on
      bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI. METHODS:
      Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or
      bivalirudin for PCI. The use of a VCD after femoral access was left to the
      operator's discretion. The effect of randomized treatment in patients who
      received a VCD was compared to that in patients with manual compression of the
      femoral access site. The primary end-point of this analysis was the 30-day
      incidence of ISAR-REACT-4 major bleeding. RESULTS: A total of 1,711 patients were
      enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188
      (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR-
      REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin,
      independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7%
      without VCD, Pint = 0.76). There were also no interactions between randomized
      treatment and VCDs with respect to any of the ischemic end-points or net clinical
      outcome (Pint > 0.56). CONCLUSIONS: In patients undergoing PCI for NSTEMI, the
      reduction of major bleeding by bivalirudin compared with UFH + abciximab was not
      affected whether a VCD was used.

PMID- 24118115
TI  - At least some protist species are not ubiquitous.
AB  - Body size is one of the main regulators of the ecological characteristics of
      living organisms, including their biogeography. The 'ubiquity hypothesis' for
      microorganisms states that they are widely distributed, if not cosmopolitan, due
      to their small size that allows passive dispersal, in contrast to large organisms
      that are limited by geographical barriers in their active dispersal. Such idea,
      summarized in the tenet 'Everything is everywhere, but the environment selects',
      has driven most of the research in biogeography for microscopic organisms in the
      last decades, spurring a debate on whether there are fundamental differences in
      the biogeography of small and large organisms or not (Fenchel & Finlay 2004;
      Foissner 2008; Hortal 2011). The strong focus on the ubiquity hypothesis may have
      been often abused to provide a rationale for otherwise descriptive work on the
      spatial distribution of microscopic organisms; nevertheless, such focus also
      provides a framework to understand the mechanisms originating and maintaining
      biodiversity in space. The reliability of the analyses on unknown and
      understudied organisms is improving, and Heger et al. (2013) is a splendid
      example on small unicellular eukaryotes of what should be done to overcome the
      major problems and ambiguities that heated the debate on the ubiquity hypothesis.

PMID- 24118116
TI  - Urban population genetics of slum-dwelling rats (Rattus norvegicus) in Salvador,
      Brazil.
AB  - Throughout the developing world, urban centres with sprawling slum settlements
      are rapidly expanding and invading previously forested ecosystems. Slum
      communities are characterized by untended refuse, open sewers and overgrown
      vegetation, which promote rodent infestation. Norway rats (Rattus norvegicus) are
      reservoirs for epidemic transmission of many zoonotic pathogens of public health
      importance. Understanding the population ecology of R. norvegicus is essential to
      formulate effective rodent control strategies, as this knowledge aids estimation
      of the temporal stability and spatial connectivity of populations. We screened
      for genetic variation, characterized the population genetic structure and
      evaluated the extent and patterns of gene flow in the urban landscape using 17
      microsatellite loci in 146 rats from nine sites in the city of Salvador, Brazil.
      These sites were divided between three neighbourhoods within the city spaced an
      average of 2.7 km apart. Surprisingly, we detected very little relatedness among
      animals trapped at the same site and found high levels of genetic diversity, as
      well as structuring across small geographical distances. Most F(ST) comparisons
      among sites were statistically significant, including sites <400 m apart.
      Bayesian analyses grouped the samples in three genetic clusters, each associated
      with distinct sampling sites from different neighbourhoods or valleys within
      neighbourhoods. These data indicate the existence of complex genetic structure in
      R. norvegicus in Salvador, linked to the heterogeneous urban landscape. Future
      rodent control measures need to take into account the spatial and temporal
      linkage of rat populations in Salvador, as revealed by genetic data, to develop
      informed eradication strategies.

PMID- 24118117
TI  - Signatures of diversifying selection at EST-SSR loci and association with climate
      in natural Eucalyptus populations.
AB  - Understanding the environmental parameters that drive adaptation among
      populations is important in predicting how species may respond to global climatic
      changes and how gene pools might be managed to conserve adaptive genetic
      diversity. Here, we used Bayesian FST outlier tests and allele-climate
      association analyses to reveal two Eucalyptus EST-SSR loci as strong candidates
      for diversifying selection in natural populations of a southwestern Australian
      forest tree, Eucalyptus gomphocephala (Myrtaceae). The Eucalyptus homolog of a
      CONSTANS-like gene was an FST outlier, and allelic variation showed significant
      latitudinal clinal associations with annual and winter solar radiation, potential
      evaporation, summer precipitation and aridity. A second FST outlier locus,
      homologous to quinone oxidoreductase, was significantly associated with measures
      of temperature range, high summer temperature and summer solar radiation, with
      important implications for predicting the effect of temperature on natural
      populations in the context of climate change. We complemented these data with
      investigations into neutral population genetic structure and diversity throughout
      the species range. This study provides an investigation into selection signatures
      at gene-homologous EST-SSRs in natural Eucalyptus populations, and contributes to
      our understanding of the relationship between climate and adaptive genetic
      variation, informing the conservation of both putatively neutral and adaptive
      components of genetic diversity. 

PMID- 24118119
TI  - Salivary IL-1beta and PGE2 as biomarkers of periodontal status, before and after
      periodontal treatment.
AB  - AIM: Interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2 ) are key
      inflammatory mediators involved in periodontitis. The purpose was to compare
      their salivary concentrations in relation to periodontal status and their changes
      after periodontal treatment, to determine their use as non-invasive diagnostic
      tools. MATERIALS AND METHODS: In this study, 74 subjects grouped in periodontally
      healthy, mild, moderate and severe periodontitis, according to clinical
      attachment level (CAL) and probing pocket depth (PPD) served as participants. IL
      1beta and PGE2 were determined in unstimulated whole saliva by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Interleukin -1beta increased with the
      severity of periodontitis with a large effect size in prediction of CAL (eta(2) 
      = 0.35, p = 0.0001). PGE2 showed an increment in mild periodontitis and another
      in moderate. A significant effect size was also found between PGE2 and PPD
      (eta(2)  = 0.12, p = 0.003). Both mediators decreased after periodontal
      treatment. With a selected threshold of 212 pg/ml, salivary IL1-beta predicted
      periodontitis with 78% sensitivity and 100% specificity. With a selected
      threshold of 121 pg/ml, salivary PGE2 predicted periodontitis with 78%
      sensitivity and 91% specificity. CONCLUSION: The high sensitivity and specificity
      of salivary IL-1beta and PGE2 in identifying periodontitis suggest a potential
      use as biomarkers for diagnosis of periodontitis presence and severity.

PMID- 24118120
TI  - Epistasis and maternal effects in experimental adaptation to chronic nutritional
      stress in Drosophila.
AB  - Based on ecological and metabolic arguments, some authors predict that adaptation
      to novel, harsh environments should involve alleles showing negative (diminishing
      return) epistasis and/or that it should be mediated in part by evolution of
      maternal effects. Although the first prediction has been supported in microbes,
      there has been little experimental support for either prediction in multicellular
      eukaryotes. Here we use a line-cross design to study the genetic architecture of
      adaptation to chronic larval malnutrition in a population of Drosophila
      melanogaster that evolved on an extremely nutrient-poor larval food for 84
      generations. We assayed three fitness-related traits (developmental rate, adult
      female weight and egg-to-adult viability) under the malnutrition conditions in 14
      crosses between this selected population and a nonadapted control population
      originally derived from the same base population. All traits showed a pattern of
      negative epistasis between alleles improving performance under malnutrition.
      Furthermore, evolutionary changes in maternal traits accounted for half of the
      68% increase in viability and for the whole of 8% reduction in adult female body
      weight in the selected population (relative to unselected controls). These
      results thus support both of the above predictions and point to the importance of
      nonadditive effects in adaptive microevolution. 

PMID- 24118122
TI  - Is overactive bladder a brain disease? The pathophysiological role of cerebral
      white matter in the elderly.
AB  - Small-vessel disease of the brain affecting the deep white matter
      characteristically manifests with neurological syndromes, such as vascular
      dementia and vascular parkinsonism. There is, however, compelling evidence to
      suggest that white matter disease can cause overactive bladder and incontinence,
      and in some patients these might be the initial manifestation. As white matter
      disease increases significantly with age, and preferentially affects the
      prefrontal deep white matter, white matter disease becomes an anatomical
      substrate in the brain etiology of overactive bladder. Treatment entails the
      management of small-vessel disease risk factors and anticholinergic drugs that do
      not easily penetrate the blood-brain barrier, to improve bladder control. In
      short, when caring for elderly overactive-bladder patients, we should look at
      both the brain and the bladder. 

PMID- 24118121
TI  - Withdrawal from extended-access cocaine self-administration results in
      dysregulated functional activity and altered locomotor activity in rats.
AB  - Much work has focused on determining the consequences of cocaine self
      administration on specific neurotransmitter systems, thus neglecting the global
      changes that occur. Previous imaging studies have focused on the effects of
      cocaine self-administration in the presence of high blood levels of cocaine, but
      have not determined the functional effects of cocaine self-administration after
      cocaine has cleared. Extended-access cocaine self-administration, where animals
      administer cocaine for 6 h each day, results in escalation in the rate of cocaine
      intake and is believed to model the transition from recreational use to addiction
      in humans. We aimed to determine the functional changes following acute (48 h)
      withdrawal from an extended-access, defined-intake self-administration paradigm
      (5 days, 40 injections/day, 6 h/day), a time point when behavioral changes are
      present. Using the 2-[(14) C]deoxyglucose method to measure rates of local
      cerebral glucose metabolism, an indicator of functional activity, we found
      reductions in circuits related to learning and memory, attention, sleep, and
      reward processing, which have important clinical implications for cocaine
      addiction. Additionally, lower levels of functional activity were found in the
      dorsal raphe and locus coeruleus, suggesting that cocaine self-administration may
      have broader effects on brain function than previously noted. These widespread
      neurochemical reductions were concomitant with substantial behavioral differences
      in these animals, highlighted by increased vertical activity and decreased
      stereotypy. These data demonstrate that behavioral and neurochemical impairments
      following cocaine self-administration are present in the absence of drug and
      persist after cocaine has been cleared. 

PMID- 24118125
TI  - Abstracts of the 22nd Annual Meeting of the German Transplantation Society.
      Frankfurt am Main, Germany. October 24-26, 2013.

PMID- 24118123
TI  - The impact of playing in matches while injured on injury surveillance findings in
      professional football.
AB  - This study aimed to analyze the frequency, nature, and consequences of
      footballers playing matches while injured, and to examine the impact on injury
      surveillance findings. High levels of inter-rater reliability and content
      validity were established for a tool designed to document players who were
      already injured at the start of a match. The tool was implemented in three
      English football teams (a Championship, League 1, and League 2 team) for one
      season, using a "time loss" definition of injury. One hundred forty-three matches
      were surveyed, revealing 102 match appearances by players who were already
      injured. Almost half of all games featured at least one injured player, with
      episodes of playing with injury occurring more frequently and lasting longer in
      League 2 players compared with higher level players. No association was observed
      between the number of injured players starting matches and match outcome [chi(2)
      (4, N = 143) = 3.27, P = 0.514]. Fifteen percent of all injury episodes captured
      were only through prospective documentation of playing while injured. The
      findings show that both traumatic and overuse injuries are managed by footballers
      through competitive matches, and have important implications for aiding
      understanding of the epidemiology of injury in professional football.

PMID- 24118126
TI  - Endoscopic approaches for pancreatobiliary diseases in patients with altered
      gastrointestinal anatomy.
AB  - Endoscopic treatment for pancreatobiliary diseases is less invasive than surgery
      and percutaneous transhepatic biliary drainage is highly beneficial to patients.
      The endoscopic approach is indicated for an increasing number of patients,
      including those who have undergone previous gastrointestinal surgery, although
      these patients face two major challenges. First, the endoscopic approach to the
      afferent loop, blind end, and the site of choledochojejunostomy is difficult with
      the use of a conventional endoscope because of the distance from the
      gastrojejunal anastomosis site, unusual anatomical features of the intestine such
      as its winding shape, and postoperative adhesion. Second, it is difficult to
      reach Vater's papilla or the site of choledochojejunostomy and to cannulate
      selectively into the pancreatic and/or biliary duct. The balloon-assisted
      endoscope (BAE), a recently developed technology, can be useful for carrying out
      endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically
      altered anatomy. ERCP using the BAE is highly effective and safe in patients with
      altered gastrointestinal anatomy, especially in patients with Roux-en-Y
      reconstruction.

PMID- 24118118
TI  - Pliocene intraspecific divergence and Plio-Pleistocene range expansions within
      Picea likiangensis (Lijiang spruce), a dominant forest tree of the Qinghai-Tibet
      Plateau.
AB  - A knowledge of intraspecific divergence and range dynamics of dominant forest
      trees in response to past geological and climate change is of major importance to
      an understanding of their recent evolution and demography. Such knowledge is
      informative of how forests were affected by environmental factors in the past and
      may provide pointers to their response to future environmental change. However,
      genetic signatures of such historical events are often weak at individual loci
      due to large effective population sizes and long generation times of forest
      trees. This problem can be overcome by analysing genetic variation across
      multiple loci. We used this approach to examine intraspecific divergence and past
      range dynamics in the conifer Picea likiangensis, a dominant tree of forests
      occurring in eastern and southern areas of the Qinghai-Tibet Plateau (QTP). We
      sequenced 13 nuclear loci, two mitochondrial DNA regions and three plastid
      (chloroplast) DNA regions in 177 individuals sampled from 22 natural populations
      of this species, and tested the hypothesis that its evolutionary history was
      markedly affected by Pliocene QTP uplifts and Quaternary climatic oscillations.
      Consistent with the taxonomic delimitation of the three morphologically divergent
      varieties examined, all individuals clustered into three genetic groups with
      intervariety admixture detected in regions of geographical overlap. Divergence
      between varieties was estimated to have occurred within the Pliocene and
      ecological niche modelling based on 20 ecological variables suggested that niche
      differentiation was high. Furthermore, modelling of population-genetic data
      indicated that two of the varieties (var. rubescens and var. linzhiensis)
      expanded their population sizes after the largest Quaternary glaciation in the
      QTP, while expansion of the third variety (var. likiangensis) began prior to
      this, probably following the Pliocene QTP uplift. These findings point to the
      importance of geological and climatic changes during the Pliocene and Pleistocene
      as causes of intraspecific diversification and range shifts of dominant tree
      species in the QTP biodiversity hot spot region. 

PMID- 24118127
TI  - Restrictive versus liberal red blood cell transfusion thresholds in very low
      birth weight infants: a systematic review and meta-analysis.
AB  - AIM: A systematic review was conducted to examine the effects of restrictive
      versus liberal red blood cell (RBC) transfusion thresholds on clinically
      important outcomes in very low birth weight (VLBW) infants. METHODS: Randomised
      controlled trials (RCTs) of varying RBC transfusion thresholds in VLBW infants
      were identified by searching MEDLINE, EMBASE, CINAHL, all of the Cochrane Library
      and other supplementary sources. Selected studies included one of the following
      outcomes: total number of red blood cell transfusions, donor exposure rate,
      cranial ultrasonographically diagnosed brain injury, retinopathy of prematurity,
      bronchopulmonary dysplasia, necrotising enterocolitis or death. Studies to be
      included were selected by two reviewers who also assessed the risk of bias of
      each trial. Data extraction and analyses were independently performed by two
      reviewers. All data were analysed using RevMan 5. RESULTS: Six RCTs were
      identified. One trial did not meet the inclusion criteria, while two had
      inadequate methodological quality. Pooled analysis of two trials showed that the
      restrictive transfusion group received a significantly lower mean number of
      transfusions per infant (mean difference (MD) -1.35, 95% confidence interval (CI)
      [-2.61, -0.09]) and donor exposure rate (MD -0.54, 95% CI [-0.93, -0.15]). No
      other statistically significant differences were observed. CONCLUSION:
      Restrictive RBC transfusion thresholds in VLBW infants may be utilised without
      incurring clinically important increases in the risk of death or major short-term
      neonatal morbidities.

PMID- 24118128
TI  - Validating report of first episode of wheezing with pediatrician-detected
      wheezing among children.

PMID- 24118130
TI  - An integrative review of the impact of indirect trauma exposure in health
      professionals and potential issues of salience for midwives.
AB  - AIMS: To explore responses to indirect trauma reported by health professionals
      and to identify issues of potential salience for midwives. BACKGROUND: Indirect
      exposure to a traumatic event can lead to the development of distressing and
      potentially enduring responses. Little is understood about the impact that
      perinatal trauma exposure could have on midwives. DESIGN: An integrative review
      design was used. DATA SOURCES: PsychInfo, Medline, PsychArticles, Web of
      Knowledge, CINAHL, MIDIRS and Scopus databases were search for papers published
      between 1980-November 2012. REVIEW METHODS: Studies providing quantitative or
      qualitative exploration of healthcare professionals' responses to indirectly
      experienced traumatic events were selected. RESULTS: Forty-two papers fulfilled
      the inclusion criteria. Four of these studies included professionals engaged in
      maternity care or exposed to traumatic perinatal events. Findings indicate
      evidence of intrusion, avoidance and arousal in healthcare professionals, with
      differing degrees of frequency. Empathy, work-related stress and the extent of
      professional experience were identified as associated with traumatic stress
      responses. CONCLUSIONS: Evidence derived from healthcare professionals suggests
      that indirect exposure to the traumatic events of recipients of care can
      sometimes elicit traumatic stress responses. Factors increasing risk for
      traumatic stress were identified as empathy and organizational stress. These
      factors hold specific salience in midwifery. Responding to trauma in a midwifery
      context, as informed by findings from other healthcare professionals, could
      adversely affect midwives' well-being, care provided to women and contribute to
      an adverse organizational climate. Large-scale research considering the
      experiences of midwives is recommended.

PMID- 24118129
TI  - Co-ordinate synthesis and protein localization in a bacterial organelle by the
      action of a penicillin-binding-protein.
AB  - Organelles with specialized form and function occur in diverse bacteria. Within
      the Alphaproteobacteria, several species extrude thin cellular appendages known
      as stalks, which function in nutrient uptake, buoyancy and reproduction.
      Consistent with their specialization, stalks maintain a unique molecular
      composition compared with the cell body, but how this is achieved remains to be
      fully elucidated. Here we dissect the mechanism of localization of StpX, a stalk
      specific protein in Caulobacter crescentus. Using a forward genetics approach, we
      identify a penicillin-binding-protein, PbpC, which is required for the
      localization of StpX in the stalk. We show that PbpC acts at the stalked cell
      pole to anchor StpX to rigid components of the outer membrane of the elongating
      stalk, concurrent with stalk synthesis. Stalk-localized StpX in turn functions in
      cellular responses to copper and zinc, suggesting that the stalk may contribute
      to metal homeostasis in Caulobacter. Together, these results identify a novel
      role for a penicillin-binding-protein in compartmentalizing a bacterial organelle
      it itself helps create, raising the possibility that cell wall-synthetic enzymes
      may broadly serve not only to synthesize the diverse shapes of bacteria, but also
      to functionalize them at the molecular level. 

PMID- 24118131
TI  - Identification of putative new tomato allergens and differential interaction with
      IgEs of tomato allergic subjects.
AB  - BACKGROUND: Tomato became one of the world-wide most consumed vegetables,
      unfortunately accompanied by an increasing risk of tomato allergy affecting
      certain people. As tomato allergic subjects show highly variable reactions in
      clinical allergy tests, it is difficult to identify cultivars or differentially
      treated tomato plants where a significant reduction in the allergenic potential
      over all subjects of a cohort can be detected. OBJECTIVE: This study was carried
      out to test the hypothesis that individual variability is based on differential
      reactions of single subjects to particular allergens in tomato fruits of plants
      with certain genetic background or cultivated under distinct conditions. METHODS:
      Proteins were extracted from tomato fruits of the previously investigated
      genotypes 76R, its mycorrhizal mutant RMC, and the cultivar Counter, fertilized
      with different forms of nitrogen in deficit or excess. 2-D immunoblots were
      carried out with sera of nine tomato allergic subjects, beforehand analysed in
      skin prick tests. RESULTS: In total, ten putative tomato allergens were
      identified in these immunoblots. No correlation was detected between individual
      skin prick test results and the quantity of positive reactions to putative
      allergens. IgEs of each subject showed reactions to nearly every identified
      putative allergen, but reactions were dependent on genotype and growth
      conditions. Among the ten putative tomato allergens, five new candidates were
      identified as follows: an endo-beta-mannanase, a pectinacetylesterase, a
      pectinesterase inhibitor, an aspartyl protease family protein and a protein of
      unknown function. CONCLUSION AND CLINICAL RELEVANCE: The hypothesis that high
      interindividual differences in allergic reactions are based on the interactions
      between the IgEs of allergic subjects with particular allergens has to be
      rejected. However, five proteins with putative clinical relevance as tomato
      allergens could be newly identified.

PMID- 24118132
TI  - Reversal of isolated hypogonadotropic hypogonadism: long-term integrity of
      hypothalamo-pituitary-testicular axis in two men is dependent on intermittent
      androgen exposure.

PMID- 24118133
TI  - Septal perforator anatomy and variability of perfusion bed by myocardial contrast
      echocardiography: a study of hypertrophic cardiomyopathy patients undergoing
      alcohol septal ablation.
AB  - OBJECTIVE: To characterize the perfusion bed of the first septal perforator by
      myocardial contrast echocardiography (MCE) in patients with hypertrophic
      cardiomyopathy undergoing alcohol septal ablation (ASA). BACKGROUND: MCE is used
      to define the septal perforator anatomy prior to ASA. Occasionally, ASA cannot be
      performed due to unfavorable septal anatomy or perfusion outside the
      interventricular septum. Despite the standard use of MCE for septal mapping,
      there are no reports describing the territory of septal perforator perfusion.
      METHODS: Forty-seven consecutive patients underwent ASA between 1/1/2004 and
      12/30/2012. Blinded individuals retrospectively evaluated patients for septal
      perforator anatomic findings. Patients were divided into 2 groups based on
      presence or absence of extra-septal perfusion (ESP) as visualized by apical views
      after intracoronary contrast injection. The groups' procedural outcomes were
      compared, including infarct size, new conduction abnormalities, and major adverse
      events. RESULTS: Over 25% demonstrated ESP, of which 83% predominantly involved
      the right ventricular (RV) moderator band. The first septal perforator (FSP) was
      statistically larger in ostial diameter (1.69 mm vs. 1.23 mm, P = 0.04) and
      numerically more likely dominant in patients with ESP (63.6% vs. 47.2%, P =
      0.22). In those with ESP, the odds ratio comparing FSP diameter of 2.0 mm to the
      mean was 1.96 (95% CI: 1.01-3.80). CONCLUSIONS: Downstream capillary perfusion
      may be discordant from epicardial territory and this study emphasizes the
      importance of MCE prior to ASA. Over 25% of our patients demonstrated ESP, most
      commonly involving the RV moderator band. The size of the FSP was the strongest
      predictor of ESP.

PMID- 24118134
TI  - A complete denture impression technique survey of postdoctoral prosthodontic
      programs in the United States.
AB  - PURPOSE: The purpose of the study was to survey program directors of postdoctoral
      prosthodontic programs in the United States regarding their programs' complete
      denture impression techniques. The key objectives of the survey were to identify
      the current trends in complete denture impression making and to determine which
      techniques and materials are taught in US postdoctoral prosthodontic programs.
      MATERIALS AND METHODS: An online survey was sent to all program directors of US
      postdoctoral prosthodontic programs. The survey comprised two sections:
      preliminary impressions and final impressions. The survey contained 22 questions
      that would take approximately 5 minutes to complete. All responses remained
      anonymous throughout the survey. RESULTS: The response rate for the survey was
      87%. A majority of the programs did not separately border mold the tray prior to
      making the preliminary impressions (82%). The impression material of choice for
      the preliminary impression was irreversible hydrocolloid (88%). Selective
      pressure was the predominantly used impression philosophy (80%). All programs
      border molded the custom tray, and 95% recorded the borders in sections. The
      material of choice for border molding the custom tray was modeling plastic
      impression compound (71%). The most commonly used impression material for the
      final impressions was polyvinylsiloxane (PVS) (42%), and the second most commonly
      used impression material was polysulphide (32%). The most common technique for
      locating the posterior palatal seal was marking intraorally and transferring onto
      the final impression (65%). Most programs routinely advised their patients not to
      wear their existing dentures for at least 24 hours before the final impressions
      were made (83%). CONCLUSIONS: Based on the results of this study, the following
      conclusions can be drawn: (1) The most commonly used material for the preliminary
      impression was irreversible hydrocolloid and for the final impression was PVS.
      (2) Modeling plastic impression compound was used by most programs to border mold
      the custom trays. (3) Selective pressure was the predominantly used impression
      philosophy. (4) A majority of the programs made a special consideration for
      excessive movable (flabby) tissue. (5) Most programs routinely advised their
      patients to not wear their existing dentures for at least 24 hours before the
      final impressions were made.

PMID- 24118135
TI  - Emotional burden of diabetes is comparable among recently diagnosed and
      previously diagnosed patients. An observation related to the DAWN2 study results.

PMID- 24118137
TI  - Early repolarization syndrome: electrocardiographic signs and clinical
      implications.
AB  - Early repolarization syndrome (ERS) was previously considered as a benign
      variant, but it has recently emerged as a risk marker for idiopathic ventricular
      fibrillation (VF) and sudden death. As measured by electrocardiogram (ECG), early
      repolarization is characterized by an elevation of the J point and/or ST segment
      from the baseline by at least 0.1 mV in at least two adjoining leads. In
      particular, early repolarization detected by inferior ECG leads was found to be
      associated with idiopathic VF and has been termed as ERS. This condition is
      mainly observed in young men, athletes, and blacks. Also, it has become evident
      that electrocardiographic territory, degree of J-point elevation, and ST-segment
      morphology are associated with different levels of risk for subsequent
      ventricular arrhythmia. However, it is unclear whether J waves are more strongly
      associated with a depolarization abnormality rather than a repolarization
      abnormality. Several clinical entities can cause ST-segment elevation. Therefore,
      clinical and ECG data are essential for differential diagnosis. At present, the
      data set is insufficient to allow risk stratification in asymptomatic
      individuals. ERS, idiopathic VF, and Brugada syndrome (known as J-wave syndromes)
      are three clinical conditions that share many common ECG features; however, their
      clinical consequences are remarkably different. This review summarizes the
      current electrocardiographic data concerning ERS with clinical implications.

PMID- 24118138
TI  - Transpulmonary correction of an isolated aortopulmonary window in an adult.
AB  - We describe the operative management of a 65-year-old patient with a congenital
      type I aortopulmonary window. At surgery, heavy calcifications on the aortic side
      of the defect, and close proximity with the left coronary ostium, prevented patch
      repair from the transaortic access. Patch closure through a combined
      transpulmonary approach was therefore required. This case illustrates unique
      features of a late-presenting aortopulmonary window.

PMID- 24118136
TI  - Yeast: a simple model system to study complex phenomena of aneuploidy.
AB  - Aneuploidy, the state of having a chromosome number different from a multiple of
      the haploid number, has been associated with diseases and developmental
      disorders. The role of aneuploidy in human disease pathology, especially in
      cancer, has been a subject of much attention and debate over the last century due
      to the intrinsic complexity of the phenomena and experimental challenges. Over
      the last decade, yeast has been an invaluable model for driving discoveries about
      the genetic and molecular aspects of aneuploidy. The understanding of aneuploidy
      has been significantly improved owing to the methods for selectively generating
      aneuploid yeast strains without causing other genetic changes, techniques for
      detecting aneuploidy, and cutting-edge genetics and 'omics' approaches. In this
      review, we discuss the contribution of studies in yeast to current knowledge
      about aneuploidy. Special emphasis is placed on experimental features that make
      yeast a simpler and efficient model to investigate the complex questions in the
      field of aneuploidy. 

PMID- 24118139
TI  - Troubling 'lived experience': a post-structural critique of mental health nursing
      qualitative research assumptions.
AB  - Qualitative studies in mental health nursing research deploying the 'lived
      experience' construct are often written on the basis of conventional qualitative
      inquiry assumptions. These include the presentation of the 'authentic voice' of
      research participants, related to their 'lived experience' and underpinned by a
      meta-assumption of the 'metaphysics of presence'. This set of assumptions is
      critiqued on the basis of contemporary post-structural qualitative scholarship.
      Implications for mental health nursing qualitative research emerging from this
      critique are described in relation to illustrative published work, and some
      benefits and challenges for researchers embracing post-structural sensibilities
      are outlined.

PMID- 24118140
TI  - Electrocardiographic findings in accessory right precordial leads in adults and
      seniors with notched S waves in lead V1-a preliminary study.
AB  - BACKGROUND: Atypical right bundle branch block (RBBB) may present with an rS
      pattern and notched S wave in lead V1 . The notched S wave may represent slowed
      conduction or delayed activation of the right ventricular conduction system or
      ventricular myocardium. METHODS: We retrospectively analyzed the QRS patterns in
      accessory right precordial leads (from V3 R to V5 R) in 15 adults/senior
      individuals with notched S wave in lead V1 . RESULTS: In the right accessory
      precordial leads, 13 showed triphasic QRS pattern with final R' wave in their QRS
      complexes. This QRS pattern in association with notched S wave in lead V1 is
      suggestive of the presence of RBBB (incomplete or complete). CONCLUSIONS: A
      notched S wave in lead V1 and in the right precordial accessory leads associated
      with a final R' wave suggests the possibility of concealed RBBB (incomplete or
      complete).

PMID- 24118141
TI  - Heritability of gonad size varies across season in a wild songbird.
AB  - Many organisms advance their seasonal reproduction in response to global warming.
      In birds, which regress their gonads to a nonfunctional state each winter, these
      shifts are ultimately constrained by the time required for gonadal development in
      spring. Gonadal development is photoperiodically controlled and shows limited
      phenotypic plasticity in relation to environmental factors, such as temperature.
      Heritable variation in the time required for full gonadal maturation to be
      completed, based on both onset and speed of development and resulting in
      seasonally different gonad sizes among individuals, is thus a crucial
      prerequisite for an adaptive advancement of seasonal reproduction in response to
      changing temperatures. We measured seasonal gonadal development in climate
      controlled aviaries for 144 great tit (Parus major) pairs, which consisted of
      siblings obtained as whole broods from the wild. We show that the extent of
      ovarian follicle development (follicle size) in early spring is highly heritable
      (h(2) = 0.73) in females, but found no heritability of the extent of testis
      development in males. However, heritability in females decreased as spring
      advanced, caused by an increase in environmental variance and a decrease in
      additive genetic variation. This low heritability of the variation in a
      physiological mechanism underlying reproductive timing at the time of selection
      may hamper genetic adaptation to climate change, a key insight as this great tit
      population is currently under directional selection for advanced egg-laying.

PMID- 24118142
TI  - Oral quercetin supplementation hampers skeletal muscle adaptations in response to
      exercise training.
AB  - We aimed to test exercise-induced adaptations on skeletal muscle when quercetin
      is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin
      exercised, placebo sedentary, and placebo exercised. Treadmill exercise training
      took place 5 days a week for 6 weeks. Quercetin groups were supplemented with
      quercetin, via gavage, on alternate days throughout the experimental period.
      Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator
      1alpha mRNA levels, mitochondrial DNA (mtDNA) content, and citrate synthase (CS)
      activity were measured on quadriceps muscle. Redox status was also quantified by
      measuring muscle antioxidant enzymatic activity and oxidative damage product,
      such as protein carbonyl content (PCC). Quercetin supplementation increased
      oxidative damage in both exercised and sedentary rats by inducing higher amounts
      of PCC (P < 0.001). Quercetin supplementation caused higher catalase (P < 0.001)
      and superoxide dismutase (P < 0.05) activity in the non-exercised animals, but
      not when quercetin is supplemented during exercise. Quercetin supplementation
      increased SIRT1 expression, but when quercetin is supplemented during exercise,
      this effect is abolished (P < 0.001). The combination of exercise and quercetin
      supplementation caused lower (P < 0.05) mtDNA content and CS activity when
      compared with exercise alone. Quercetin supplementation during exercise provides
      a disadvantage to exercise-induced muscle adaptations. 

PMID- 24118143
TI  - Eruptive self-resolving keratoacanthomas developing after treatment with
      photodynamic therapy and microdermabrasion.

PMID- 24118144
TI  - Plus ca change, plus c'est la meme chose.

PMID- 24118145
TI  - What does personality tell us about working in the bush? Temperament and
      character traits of Australian remote allied health professionals.
AB  - OBJECTIVE: To describe the personality (temperament and character traits) of
      remote Australian allied health professionals (AHPs). Recent research shows that
      health professionals can be differentiated by personality traits but little is
      known about the personality traits of AHPs. DESIGN: Cross-sectional (online)
      survey design with snowball sampling of participants. SETTING AND PARTICIPANTS:
      Australian AHPs (N = 561; women, n = 502) classified into Remote (n = 266), Not
      Remote (n = 295). MAIN OUTCOME MEASURE(S): Demographic variables and the
      Temperament and Character Inventory (TCI R-140). RESULTS: Remote AHPs were higher
      in novelty seeking (P = 0.037) and self-transcendence (P = 0.042). Remote women
      were lower in harm avoidance (P = 0.042). Older remote AHPS were lower in reward
      dependence (P = 0.001); younger remote AHPs were lower in self directedness (P =
      0.001) and higher in harm avoidance (P < 0.001). Women were more reward dependent
      (P < 0.001) and cooperative (P = 0.008) than men. CONCLUSIONS: The sample
      demonstrated personality trait levels aligned with research on rural doctors and
      nurses and which might be advantageous for working in a challenging environment.
      Exploring the more stable nature of temperament traits coupled with the
      modifiable potential of character traits provides new insight into people who
      choose to work as a remote AHP. These findings might contribute to a better
      understanding of the personality trends in these AHPs which might provide clues
      to improve recruitment and retention strategies.

PMID- 24118146
TI  - Is the National Registration website (Australian Health Practitioner Regulation
      Agency) effective in tracking Australian medical graduates' rural work?
AB  - OBJECTIVE: This study compared rural location identified through the National
      Registration (AHPRA) registry with location obtained through labour-intensive
      personal contact. DESIGN: Longitudinal cohort study with two methods to identify
      the work locations of medical graduates from The Rural Clinical School of Western
      Australia (RCSWA). PARTICIPANTS: Consenting alumni from the University of Western
      Australia and the University of Notre Dame Fremantle participating in RCSWA
      between 2002 and 2009 inclusive and available to contact in 2011. MAIN OUTCOME
      MEASURE: Percentage location matches between two contact methods. RESULTS: There
      was 80% agreement for principal suburb, 92% agreement for principal city and 94%
      agreement for principal state between RCSWA personal contact and the AHPRA
      registry. AHPRA identified nearly two times as many graduate locations. However,
      there was only 31% agreement for a rural placement location (of any length). In
      more detail, for year-long rural placement, personal contact was 88% concordant
      with AHPRA; work six months or more were less concordant (44% agreement); work
      less than six months were not concordant (4% agreement). CONCLUSIONS: AHPRA data
      matched RCSWA alumni data only for graduates in full-time rural work. Since
      medical alumni spend up to 10 years in pre-vocational and vocational training,
      which includes many rural options, personal contact was able to pick up the
      myriad of rural choices, whereas the AHPRA database was not sensitive enough to
      identify them. Until graduates have stably finished training, the optimal method
      to identify rural work is through personal contact but statistical correction for
      missing data needs to be considered.

PMID- 24118147
TI  - What small rural emergency departments do: a systematic review of observational
      studies.
AB  - OBJECTIVE: Small rural emergency facilities are an important part of emergency
      care in many countries. We performed a systematic review of observational studies
      to determine what is known about the patients these small rural emergency
      facilities treat, what types of interventions they undertake and how well they
      perform. METHODS: Pubmed/Medline and Embase databases were systematically
      reviewed between 1980 and the present. Studies were included if they described
      hospital-affiliated emergency care facilities which were open 24-hours every day,
      and described themselves as rural, non-urban or non-metropolitan. Studies were
      excluded if facilities saw more than 15,000 patients annually. Study quality was
      assessed using 12 previously described indicators. Key activity and performance
      data were reported for individual studies but not numerically combined between
      studies. RESULTS: The search strategy found 19 studies that included quantitative
      data on activity and performance. Nine studies were from Canada, six were from
      Australia and four from the United States. The settings and scales used varied
      widely. Few studies adhered to methodological recommendations. The most common
      presentation was for injury or poisoning (30-53%). The number of patients
      requiring attention within 15 min was small (2.5-2.8%). Nurses treated many
      patients without physician input. CONCLUSIONS: There is only enough evidence in
      the literature to make the most basic inferences about what small rural emergency
      departments do. To allow evidence-based improvement, descriptive studies must
      employ measures and methods validated in the wider emergency medicine literature,
      and other research techniques should be considered.

PMID- 24118148
TI  - Recombinant tissue plasminogen activator (rt-PA) utilisation by rural clinicians
      in acute ischaemic stroke: a survey of barriers and enablers.
AB  - OBJECTIVE: This paper identified barriers which prevent rural health care
      providers from utilising rt-PA in acute ischaemic stroke and proposes possible
      support mechanisms to increase its utilisation. METHODS: This descriptive study
      uses data from anonymous surveys distributed to health care providers involved in
      acute stroke patient care in three rural hospitals with rt-PA pathways.
      Saturation sampling was used. Surveys gathered self assessed ratings of
      experience, practice environment, attitudes, existing support, barriers and
      possible enablers regarding rt-PA use in acute stroke. RESULTS: Physicians
      reported the strongest barriers to the use of rt-PA in acute stroke as pre
      hospital delays (91%), risk of intracerebral haemorrhage (ICH) (73%) and clinical
      diagnostic uncertainty (60%). They reported high levels of confidence in the
      support received from their stroke units (90%). Nurses identified a poor level of
      stroke education and knowledge on rt-PA utilisation in acute stroke. A third of
      nurses could correctly list six different stroke signs. The risk of ICH following
      rt-PA administration in stroke was also a significant barrier for nurses.
      Response rate from physicians was 26% (10/38) and 19% (13/69) for nurses.
      CONCLUSIONS: To reduce barriers to rt-PA utilisation in rural facilities
      physicians require education on the calculated risk of ICH as well as exposure
      and experience to improve their ability to confidently diagnose stroke patients
      who are eligible for rt-PA treatment. Education for nurses on symptoms of stroke
      and rt-PA utilisation and administration is recommended.

PMID- 24118149
TI  - Diabetic major amputation in Far North Queensland 1998-2008: what is the Gap for
      Indigenous patients?
AB  - OBJECTIVE: To examine demographic and clinical characteristics of diabetic
      patients undergoing diabetes-related major amputation in Far North Queensland to
      identify those at risk. DESIGN: A cohort was examined for differences between
      Indigenous and non-Indigenous groups in age, co-morbidities, indication for
      amputation and mortality. Attendance at the High Risk Foot Service was also
      reported. SETTING: Far North Queensland. PARTICIPANTS: individuals with major
      amputations between 1998 and 2008. MAIN OUTCOME MEASURES: Diabetes-related major
      amputations and mortality. RESULTS: Of the 143 individuals who underwent major
      amputation during the study period, 52% were Indigenous. On average, Indigenous
      amputees were 14 years younger than non-Indigenous amputees. There were more
      female Indigenous amputees compared with Indigenous male amputees. Indigenous
      amputees were more likely to suffer from chronic kidney disease (P < 0.000) and
      reside in a remote community (P < 0.000). Sepsis as an indication for amputation
      was more frequent in Indigenous subjects (P = 0.019). There was no statistically
      significant difference in mortality related to the procedure between Indigenous
      and non-indigenous amputees. CONCLUSION: Indigenous patients with renal disease
      living in remote communities are at higher risk of developing limb-threatening
      diabetic foot complications. Further improvements in self-care, diabetes
      management and foot-care are required to reduce major amputation rates,
      particularly for those residing in remote areas.

PMID- 24118150
TI  - An exploration of the priority remote health personnel give to the development of
      the Indigenous Health Worker oral health role and why: unexpected findings.
AB  - OBJECTIVE: This research was undertaken to explore the priority given by remote
      area health personnel to the development of the oral health role of Indigenous
      Health Workers and the rationale for this prioritisation. DESIGN: Semistructured
      individual interviews and focus group interviews were undertaken with remote area
      health personnel working alongside Indigenous Health Workers. SETTING: Three
      Indigenous community clinics and two regional centres of remote northern
      Australia. PARTICIPANTS: Interviews were conducted with 32 remote health
      personnel (11 dental, 14 nursing, 5 medical and 2 allied health personnel).
      RESULTS: The findings highlight the strong support found among remote health
      personnel for the development of the Indigenous Health Worker oral health role
      emphasising not only the perceived high impact of oral disease on the health of
      community members and community health resources, but also on the clinical
      practice of remote health personnel. CONCLUSION: In identifying the high priority
      given to the development of this role, the study has also highlighted the impact
      of oral disease on the practice of remote health personnel and the need to
      develop training for remote health personnel to respond to oral disease.

PMID- 24118151
TI  - Colectomies performed at a rural Australian hospital: a 7-year analysis.
AB  - INTRODUCTION: Little published data exists documenting the reasons for and
      outcomes of colectomies in rural Australia. It remains unclear whether patient
      characteristics, diagnoses, complications and outcomes differ to metropolitan
      locations. METHODS: A retrospective review of prospectively collected data for
      patients coded with International Classification of Diseases procedure code block
      934 and 935 (colectomies) performed at Wimmera Health Care Group: Horsham Campus
      between July 2004 and July 2011. Records were additionally sought from transfer
      hospitals. RESULTS: Two hundred thirty-eight colectomies were performed over the
      7-year period: 164 for a colorectal cancer diagnosis, 74 for a non-colorectal
      cancer diagnosis. For the colorectal cancer colectomies, 80.5% were elective and
      19.5% emergency. There were five (3.0%) intraoperative complications.
      Postoperatively, there were 16 (9.8%) surgical complications. There was a 3.7%
      return to theatre rate and a 3.0% unplanned readmission rate. There were no
      anastomotic leaks. The perioperative mortality rate was 5.5%. For the non
      colorectal cancer colectomies, 85.1% were emergency and 14.9% elective. There
      were five (6.8%) intraoperative complications. Postoperatively, there were 14
      (18.9%) surgical complications. There was a 12.2% return to theatre rate, a 5.4%
      unplanned readmission rate and three anastomotic leaks. The perioperative
      mortality rate was 10.8%. CONCLUSIONS: The outcomes and complications for
      colectomies appear similar to the accepted standard of surgery in other rural and
      metropolitan centres. Areas have been identified for improved surgical
      performance at Wimmera Health Care Group: Horsham Campus.

PMID- 24118152
TI  - Zoonoses in rural veterinarians in the central region of Argentina.
AB  - OBJECTIVE: To estimate the frequency of zoonoses in rural veterinarians and to
      search for risk factors. DESIGN: Cross-sectional study based on an anonymously
      answered structured questionnaire. SETTING: The interviewees participated in
      mandatory continuing education classes scheduled throughout the province by the
      College of Veterinary Surgeons. PARTICIPANTS: Overall, 741 professionals were
      surveyed, and 75.8% (n = 562) of them completed the structured questionnaire.
      MAIN OUTCOME MEASURES: Cumulative incidence (CIR) and incidence density (IDR)
      rates, standardised rates, chi(2) , Student's t-test, Pearson's correlation
      coefficient and logistic regression. RESULTS: The CIR for all zoonoses was 34.1%
      (brucellosis, 29.1%; toxoplasmosis, 2.1%; leptospirosis, 0.6%; tuberculosis,
      0.6%; anthrax, 0.6%; ringworm, 0.4%; other, 0.6%). The IDR for the period 1964
      2008 was estimated to be 20.7% (19.5% for brucellosis). The brucellosis IDR
      decreased between 1964 and 2008 and was higher during early post-graduation. The
      risk of brucellosis was associated with the number of years of practice and the
      geographical area. Sixty-nine respondents had at least one day of absence from
      work (24.0 +/- 27.8 days). CONCLUSIONS: A high frequency of zoonoses was reported
      by veterinarians with a large animal practice. Although the rate of zoonoses may
      be decreasing, further studies are needed to confirm this finding. A joint effort
      of all institutions is needed to prevent zoonoses among private practitioners.

PMID- 24118153
TI  - Pufferfish attack on Thursday Island.
AB  - In rural Australia animal attacks and bites are an increasingly common
      phenomenon. The pufferfish is native to the north-eastern coast of Australia and
      is becoming increasingly tempted closer ashore. We present the first case and
      review of the literature of a vicious fish bite from this animal in a child in
      rural Australia. 

PMID- 24118154
TI  - Patient safety 2012: reporting in from the bedside of a regional Australian
      hospital.

PMID- 24118155
TI  - Some success for a 12th National Rural Health Conference priority.

PMID- 24118156
TI  - Laparoendoscopic reduction of sigmoidorectal intussusception.

PMID- 24118157
TI  - Can donors with high donor risk indices be used cost-effectively in liver
      transplantation in US Transplant Centers?
AB  - In an effort to quantify the impact of donor risk factors on recipient outcomes,
      the donor risk index (DRI) was developed. A high DRI correlates with poorer post
      transplant survival. In this study, high-DRI donors are classified as those
      having DRIs >2.0, while low-DRI donors have DRIs <2.0. The aim of this study was
      to evaluate the cost-effectiveness of high-DRI donor use in US Transplant
      Centers. A Markov-based decision analytic model was created to simulate outcomes
      for an allocation scheme using only low-DRI donors versus a scheme using both low
      and high-DRI donors. Baseline values and ranges were determined from published
      data and Medicare cost data. Sensitivity analyses were conducted to test model
      strength and parameter variability. An allocation scheme in which only low-DRI
      donors were used generated 5.2 quality-adjusted life years (QALYs) at a cost of
      $83 000/QALY. An allocation scheme using both low- and high-DRI donors generated
      5.9 QALYs at a cost of $66 000/QALY. Sensitivity analyses supported the use of an
      allocation scheme using both low- and high-DRI donors. The overall contribution
      of high-DRI grafts to the donor pool and the resultant reduction in wait-list
      mortality make them cost-effective. 

PMID- 24118159
TI  - Multiple microscopic approaches demonstrate linkage between chromoplast
      architecture and carotenoid composition in diverse Capsicum annuum fruit.
AB  - Increased accumulation of specific carotenoids in plastids through plant breeding
      or genetic engineering requires an understanding of the limitations that storage
      sites for these compounds may impose on that accumulation. Here, using Capsicum
      annuum L. fruit, we demonstrate directly the unique sub-organellar accumulation
      sites of specific carotenoids using live cell hyperspectral confocal Raman
      microscopy. Further, we show that chromoplasts from specific cultivars vary in
      shape and size, and these structural variations are associated with carotenoid
      compositional differences. Live-cell imaging utilizing laser scanning confocal
      (LSCM) and confocal Raman microscopy, as well as fixed tissue imaging by scanning
      and transmission electron microscopy (SEM and TEM), all demonstrated
      morphological differences with high concordance for the measurements across the
      multiple imaging modalities. These results reveal additional opportunities for
      genetic controls on fruit color and carotenoid-based phenotypes. 

PMID- 24118160
TI  - 18F-Fluorodeoxyglucose uptake and clinicopathological features of recurrent or
      metastatic endometrial stromal sarcoma.
AB  - AIM: Maximum standardized uptake value on (18) F-fluorodeoxyglucose positron
      emission tomography was evaluated as a predictive surrogate marker in developing
      treatment strategies for recurrent or metastatic endometrial stromal sarcoma.
      METHODS: Clinical information was obtained from records of patients with
      recurrent or metastatic endometrial stromal sarcoma who underwent surgery or
      biopsy following (18)F-fluorodeoxyglucose positron emission tomography.
      Pathological features - including estrogen receptor, progesterone receptor and Ki
      67 expression - were immunohistochemically evaluated. We classified lesions as
      'positron emission tomography positive' if the maximum standardized uptake value
      was 3.0 or higher. Clinicopathological features were compared between patients
      with positive and negative positron emission tomography findings by using the
      chi(2)-test. RESULTS: Among eight recurrent and one metastatic endometrial
      stromal sarcoma patients, four (44%) had positron emission tomography-positive
      findings. Two positron emission tomography-positive patients were estrogen
      receptor negative and the five positron emission tomography-negative patients
      were estrogen receptor positive (P = 0.073). The Ki-67 index was 10% or higher in
      the four positron emission tomography-positive patients, but less than 5% in the
      five positron emission tomography-negative patients (P = 0.003). Three patients
      with positron emission tomography-positive tumors received more aggressive
      treatment (e.g. cytotoxic chemotherapy and additional surgery) than did those
      with positron emission tomography-negative tumors. One patient who died of
      disease had positron emission tomography-positive tumors, was negative for
      estrogen and progesterone receptors, and had a 20% Ki-67 index. CONCLUSION: (18)F
      Fluorodeoxyglucose uptake was associated with tumor biology of recurrent or
      metastatic endometrial stromal sarcoma. (18)F-fluorodeoxyglucose-positron
      emission tomography was useful for developing treatment strategies for recurrent
      or metastatic endometrial stromal sarcoma.

PMID- 24118158
TI  - Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a
      role in tolerance induction?
AB  - BACKGROUND: Decreased serum food-specific IgA antibodies have been associated
      with allergic disease in cross-sectional, case-control studies. The purpose of
      this study was to prospectively compare egg-white-(EW)-specific IgA and IgA2
      levels between egg-allergic children and children tolerating egg. METHODS:
      Seventeen egg-allergic children were followed prospectively. Total IgA, EW
      specific IgA, and EW-specific IgA2 levels were measured in their sera with a
      sensitive ELISA. As negative controls were used children with no previous history
      of egg allergy. Egg-allergic children with or without concomitant milk allergy
      were evaluated as additional controls with measurement of casein-specific IgA.
      RESULTS: After 2.5 +/- 0.9 yrs, nine out of the 17 allergic children became
      tolerant and eight remained allergic to baked egg. Baseline EW-specific IgA2
      levels were significantly lower in the egg-allergic subjects (median 23.9 ng/ml)
      compared with the negative control subjects (99.4 ng/ml) and increased
      significantly by 28% over the study time period in eight out of the nine allergic
      children that became tolerant to baked egg. There was no significant change over
      time in EW-specific IgA in any of the study groups. Non-milk-allergic subjects
      with concomitant egg allergy had almost threefold higher casein-specific IgA
      levels than the milk- and egg-allergic subjects (p = 0.025). CONCLUSIONS: These
      results suggest a potential role for allergen-specific IgA2 antibodies in the
      induction of food tolerance. Furthermore, they support the hypothesis that
      immature or impaired production of allergen-specific IgA2 may be associated with
      the pathophysiology of food allergy, a defect that seems to be selective for the
      culprit allergen.

PMID- 24118161
TI  - Corrosive and cytotoxic properties of compact specimens and microparticles of Ni
      Cr dental alloy.
AB  - PURPOSE: Nickel-chromium (Ni-Cr) dental alloys have been widely used in
      prosthodontic practice, but there is a permanent concern about their
      biocompatibility due to the release of metal ions. This is especially important
      when Ni-Cr metal microparticles are incorporated into gingival tissue during
      prosthodontic procedures. Therefore, the aim of this study was to examine and
      compare the corrosion and cytotoxic properties of compact specimens and
      microparticles of Ni-Cr dental alloy. MATERIALS AND METHODS: Ni-Cr alloy,
      Remanium CSe bars (4 mm diameter), were made by the standard casting method and
      then cut into 0.5-mm-thick disks. Metal particles were obtained by scraping the
      bars using a diamond instrument for crown preparation. The microstructure was
      observed by an optical microscope. Quantitative determination and morphological
      and dimensional characterization of metal particles were carried out by a
      scanning electron microscope and Leica Application Suite software for image
      analysis. Corrosion was studied by conditioning the alloy specimens in the RPMI
      1640 medium, containing 10% fetal calf serum in an incubator with 5% CO2 for 72
      hours at 37 degrees C. Inductively coupled plasma-optical emission spectrometry
      was used to assess metal ion release. The cytotoxity of conditioning medium (CM)
      was investigated on L929 cells using an MTT test. One-way ANOVA was used for
      statistical analysis. RESULTS: After casting, the microstructure of the Remanium
      CSe compact specimen composed of Ni, Cr, Mo, Si, Fe, Al, and Co had a typical
      dendritic structure. Alloy microparticles had an irregular shape with a wide size
      range: from less than 1 MUm to more than 100 MUm. The release of metal ions,
      especially Ni and Mo from microparticles, was significantly higher, compared to
      the compact alloy specimen. The CM prepared from compact alloy was not cytotoxic
      at any tested dilutions, whereas CM from alloy microparticles showed dose
      dependent cytotoxicity (90% CM and 45% CM versus control; p < 0.005). CONCLUSION:
      Ni-Cr microparticles showed less corrosion resistance and lower biocompatibility
      than compact alloy. This could affect health on long-term exposure, especially in
      sensitized individuals.

PMID- 24118163
TI  - Relationship between self-compassion and emotional intelligence in nursing
      students.
AB  - Nursing focuses on meeting physical, social and emotional health-care needs of
      individuals, families and society. In health care, nurses directly communicate
      with patients and try to empathize with them. Nurses give care under emotionally
      intense conditions where the individual undergoes pain and distress. Research is
      aimed at analysing the correlation of self-compassion and emotional intelligence
      of nursing students. The population of the research consisted of all the
      undergraduate students (571 students) of the 2010-2011 fall semester of the
      department of nursing. An information form, Self-compassion Scale and Emotional
      Intelligence Assessment Scale were utilized to obtain data for the research. For
      the assessment of the findings of research, Statistical Package for Social
      Sciences 16.0 for Windows was utilized for statistical analysis. Results
      indicated that there is a correlation between self-compassion and emotional
      intelligence and that emotional intelligence, which includes the individual
      perceiving one's emotions and using the knowledge one gained from them to
      function while directing thoughts, actions and professional applications, has
      positive contributions to the features of nurses with developed self-compassion. 

PMID- 24118162
TI  - Molecular epidemiology of Legionnaires' disease in Israel.
AB  - National surveillance of Legionnaires' disease (LD) is important to inform
      control measures and facilitate international networking for timely reporting.
      This study is the first to describe the molecular epidemiology of LD in Israel.
      Case notifications for 2006-2011, collated through mandatory reporting, were
      identified and demographic, clinical and laboratory data were extracted.
      Unrelated clinical and environmental Legionella pneumophila strains were
      characterized using standard procedures, Dresden panel of monoclonal antibodies
      and the ESCMID Study Group for Legionella Infections (ESGLI) Sequence-Based
      Typing scheme. In all, 294 cases were reported (crude incidence 0.67 cases/100
      000; age-standardized incidence 1/100 000). LD epidemiological trends and
      features largely resembled those of the EU, except for a larger proportion of
      nosocomial cases. Of 28 clinical and 23 environmental strains analysed, 71.4% and
      21.7% were serogroup (sg) 1 and the most common immunological subgroup was
      OLDA/Oxford (64%). Of the clinical strains, OLDA/Oxford, ST1 was the most common
      (43%) followed by Allentown/France, ST40 (14%). The unusual sg 3 ST338 was found
      in 17.4% of environmental strains. Novel STs were detected amongst 23.5% of
      strains. These findings warrant further molecular investigation. Molecular
      epidemiology data generated from neighbouring countries newly adopting the ESGLI
      typing scheme for L. pneumophila contribute to understanding of regional strain
      diversity.

PMID- 24118164
TI  - Extracardiac ice formation during second-generation 28 mm cryoballoon ablation of
      atrial fibrillation.

PMID- 24118165
TI  - Multicenter, randomized, sham-controlled study on the efficacy of magnetic
      stimulation for women with urgency urinary incontinence.
AB  - OBJECTIVES: To evaluate the efficacy and safety of magnetic stimulation for the
      treatment of urinary incontinence in women with overactive bladder. METHODS: A
      total of 151 women with urgency incontinence were randomized to the active
      stimulation group or the sham stimulation group in a 2:1 order. An armchair type
      magnetic stimulator was used for 25-min magnetic stimulation twice a week, with
      the maximum magnetic flux density of 560 mT peak at 10 Hz. The sham device was
      set to deliver in a 5-s "on"-5-s "off" pulsing manner with the maximum intensity
      of 20.4% of active stimulation at 1 Hz. The study consisted of a baseline period
      for 1 week, and a treatment period for 6 weeks. The primary end-point was the
      number of leaks/week from the bladder diary. The secondary end-points were the
      number of voids and urgency/24 h, mean and maximum voided volume, and the quality
      of life assessment. RESULTS: Changes from baseline in the active and sham group,
      respectively, were -13.08 +/- 11.00 and -8.68 +/- 13.49 in leaks/week (P =
      0.038), -2.65 +/- 2.52 and -1.53 +/- 2.39 in number of urgency/24 h (P = 0.011),
      and 14.03 +/- 34.53 mL and -4.15 +/- 40.60 mL in mean voided volume (P = 0.0056).
      As for safety, except for diarrhea and constipation, no patients experienced any
      device-related adverse event. CONCLUSIONS: Magnetic stimulation is effective for
      the treatment of urgency incontinence in female patients with overactive bladder.

PMID- 24118166
TI  - Serum antibody against Helicobacter pylori FlaA and risk of gastric cancer.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for
      gastric cancer (GC); however, only a minority of infected individuals develops
      GC. We aim to assess the association between serostatus of antibody against H.
      pylori flagellin A (FlaA) and risk of GC and to evaluate the value of serum FlaA
      antibody as a novel screening biomarker for GC risk. METHODS: A hospital-based
      case-control study including 232 cases and 264 controls was conducted. Logistic
      regression was adopted to analyze the association between the serostatus of FlaA
      antibody and risk of GC. Serum FlaA antibody was measured by an enzyme-linked
      immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve was
      used to evaluate the screening efficacy and to identify a cutoff point of serum
      FlaA antibody level. RESULTS: Helicobacter pylori infection was associated with
      an increased risk of GC (p = .007). A positive association between serum FlaA
      antibody and GC risk was observed in overall subjects and H. pylori-positive
      subjects (OR [95% CI]: 6.8 [4.3-10.7] and 6.9 [3.6-13.4], respectively; p <
      .001). The seropositivity of FlaA antibody was strongly related to GC risk in a
      dose-dependent manner (p for trend < .001). The optimal cutoff value (OD) was
      0.1403, providing a sensitivity of 74.1% and a specificity of 64.4%. The area
      under the ROC curve (AUC) was 0.74 in overall subjects and 0.73 in H. pylori
      positive subjects, respectively. CONCLUSIONS: FlaA was an independent risk factor
      for H. pylori-related GC. Serum FlaA antibody may serve as a novel noninvasive
      biomarker for early detection of GC.

PMID- 24118167
TI  - Concerted transfer of the virulence Ti plasmid and companion At plasmid in the
      Agrobacterium tumefaciens-induced plant tumour.
AB  - The plant pathogen Agrobacterium tumefaciens C58 harbours three independent type
      IV secretion (T4SS) machineries. T4SST-DNA promotes the transfer of the T-DNA to
      host plant cells, provoking tumour development and accumulation of opines such as
      nopaline and agrocinopines. T4SSpTi and T4SSpAt control the bacterial conjugation
      of the Ti and At plasmids respectively. Expression of T4SSpTi is controlled by
      the agrocinopine-responsive transcriptional repressor AccR. In this work, we
      compared the genome-wide transcriptional profile of the wild-type A. tumefaciens
      strain C58 with that of its accR KO-mutant to delineate the AccR regulon. In
      addition to the genes that encode agrocinopine catabolism and T4SSpTi , we found
      that AccR also regulated genes coding for nopaline catabolism and T4SSpAt .
      Further opine detection and conjugation assays confirmed the enhancement of
      nopaline consumption and At plasmid conjugation frequency in accR. Moreover, co
      regulation of the T4SSpTi and T4SSpAt correlated with the co-transfer of the At
      and Ti plasmids both in vitro and in plant tumours. Finally, unlike T4SSpTi ,
      T4SSpAt activation does not require quorum-sensing. Overall this study highlights
      the regulatory interplays between opines, At and Ti plasmids that contribute to a
      concerted dissemination of the two replicons in bacterial populations colonizing
      the plant tumour. 

PMID- 24118168
TI  - Is research in substance abuse undervalued?

PMID- 24118169
TI  - Muscle MRI in female carriers of emerinopathy.

PMID- 24118170
TI  - 'Restless bladder' and the boundaries of the restless legs syndrome.

PMID- 24118173
TI  - In vitro intrinsic optical imaging can be used for source determination in
      cortical slices.
AB  - In the last decades intrinsic optical imaging has become a widely used technique
      for monitoring activity in vivo and in vitro. It is assumed that in brain slices
      the source of intrinsic optical signals (IOSs) is the change in light scattering
      caused by cell swelling or shrinkage. The aim of the present study was to find a
      correlation between electrical activity and parallel optical characteristics,
      elicited by 4-aminopyridine-containing or Mg(2+) -free medium in rat cortical
      brain slices. Electrophysiological signals and reflected light alterations were
      recorded during spontaneous seizure activity. Current source density (CSD)
      analysis was performed on the electrophysiological records. Direct correlation
      analysis of IOS to CSD was made, and source distribution provided by IOS and CSD
      methods was compared by determining Matthews correlation coefficient. The gradual
      development of seizure-like activity elicited the reduction of light reflectance.
      The main findings of our experiments are that long-term epileptiform activity
      resulted in persistent alteration in IOSs of brain slices. The observed IOS
      pattern remained stable after 1 h incubation in convulsants. The pattern of IOS
      shows good correlation with the data obtained from the CSD analysis. Persistent
      IOS changes provide information about the area-specific changes of basic
      excitability, which can serve as a background for ictal and interictal-like
      epileptiform activity. We can conclude that changes in IOSs correlate well with
      electrophysiological recordings under different conditions. Our experiments
      provide evidence that underlying synchronised neuronal processes produce parallel
      alterations in IOSs and electrophysiological activity.

PMID- 24118172
TI  - Highly expressed cytoplasmic FcepsilonRIbeta in human mast cells functions as a
      negative regulator of the FcRgamma-mediated cell activation signal.
AB  - BACKGROUND: We recently reported that the interaction between Lyn and
      FcepsilonRIbeta is indispensable for FcepsilonRI-mediated human mast cell (MC)
      activation and that FcepsilonRIbeta functions as an amplifier of FcepsilonRI
      mediated activation signal. Some of FcepsilonRIbeta in cytoplasm appeared not to
      be co-localized with FcepsilonRIalpha. The function of FcepsilonRIbeta in the
      cytoplasm remains unknown. METHODS: The localization of FcepsilonRIbeta and
      FcepsilonRIalpha in giant papillae specimens from patients with allergic
      keratoconjunctivitis and of FcepsilonRIbeta, FcepsilonRIalpha, and Lyn in
      cultured human MCs was examined using confocal microscopy. FcepsilonRIbeta was
      overexpressed using an adenovirus vector system. Mediators were measured by
      enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS: In the
      subepithelial region, FcepsilonRIbeta was mainly localized in the cell membrane
      of MCs. In the perivascular region, FcepsilonRIbeta expression was scattered
      throughout the cytoplasm and in the cell membrane of MCs. Overexpression of
      FcepsilonRIbeta in MCs mainly increased its cytoplasmic expression and slightly
      up-regulated cell surface FcepsilonRI expression. However, overexpression of
      FcepsilonRIbeta in MCs resulted in down-regulation of the tyrosine
      phosphorylation levels of FcepsilonRIbeta and Syk and down-regulation of the
      Ca(2+) influx soon after FcepsilonRI aggregation and then resulted in down
      regulation of degranulation, PGD2 synthesis, and production of a set of
      cytokines. This negative regulatory effect may be due to inhibition of the
      redistribution of Lyn to small patches within the plasma membrane. CONCLUSION:
      Cytoplasmic FcepsilonRIbeta, which is not co-localized with FcepsilonRIalpha, may
      function as a negative regulator, as it can capture important signalling
      molecules such as Lyn.

PMID- 24118174
TI  - Long-term outcomes of drug-eluting stent therapy for in-stent restenosis versus
      de novo lesions.
AB  - BACKGROUND: Drug-eluting stents (DES) are currently the most popular treatment
      modality for restenosis in bare metal stents and DES. This study compares risks
      of adverse cardiovascular events between DES-treated in-stent restenosis (ISR)
      and de novo lesions, an area that has not been systematically studied thus far.
      METHODS AND RESULTS: One thousand three hundred consecutive ISR patients were
      compared with 27,211 patients with de novo lesions who underwent DES treatment
      during the same period at the Fu Wai Hospital in Beijing. Angiographic success
      rate was similar between the ISR and de novo groups (98.0% vs. 98.2%; P = 0.61).
      Using logistic regression to derive the propensity score model, 1,266 matched
      patient pairs were compared. In this adjusted model, the rate of target lesion
      revascularization (TLR) was significantly higher in the ISR group (19.19% vs.
      2.37%; P < 0.01) during an average 17-month follow-up, while rates of cardiac
      death and myocardial infarction (MI) were similar (0.71% vs. 0.79%; P = 0.93 and
      3.48% vs. 1.26%; P = 0.13, respectively) between groups. In multivariate
      regression analysis, ISR was predictive of TLR, but not of cardiac death and MI.
      CONCLUSION: Compared with those with de novo lesions, patients with ISR had a
      higher revascularization rate after DES treatment but no significant difference
      in rates of cardiac death and MI.

PMID- 24118175
TI  - Treatment of wheezing in Brazilian infants in the first year of life.

PMID- 24118176
TI  - Lack of parallel genetic patterns underlying the repeated ecological divergence
      of beach and stream-spawning kokanee salmon.
AB  - Recent progress in methods for detecting adaptive population divergence in situ
      shows promise for elucidating the conditions under which selection acts to
      generate intraspecific diversity. Rapid ecological diversification is common in
      fishes; however, the role of phenotypic plasticity and adaptation to local
      environments is poorly understood. It is now possible to investigate genetic
      patterns to make inferences regarding phenotypic traits under selection and
      possible mechanisms underlying ecotype divergence, particularly where similar
      novel phenotypes have arisen in multiple independent populations. Here, we
      employed a bottom-up approach to test for signatures of directional selection
      associated with divergence of beach- and stream-spawning kokanee, the obligate
      freshwater form of sockeye salmon (Oncorhynchus nerka). Beach- and stream
      spawners co-exist in many post-glacial lakes and exhibit distinct reproductive
      behaviours, life-history traits and spawning habitat preferences. Replicate
      ecotype pairs across five lakes in British Columbia, Canada were genotyped at 57
      expressed sequence tag-linked and anonymous microsatellite loci identified in a
      previous genome scan. Fifteen loci exhibited signatures of directional selection
      (high FST outliers), four of which were identified in multiple lakes. However,
      the lack of parallel genetic patterns across all lakes may be a result of: 1) an
      inability to detect loci truly under selection; 2) alternative genetic pathways
      underlying ecotype divergence in this system; and/or 3) phenotypic plasticity
      playing a formative role in driving kokanee spawning habitat differences. Gene
      annotations for detected outliers suggest pathogen resistance and energy
      metabolism as potential mechanisms contributing to the divergence of beach- and
      stream-spawning kokanee, but further study is required. 

PMID- 24118177
TI  - The number needed to treat to prevent mortality and cirrhosis-related
      complications among patients with cirrhosis and HCV genotype 1 infection.
AB  - Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk
      for complications following sustained virological response (SVR). Therefore, we
      aimed to evaluate treatment efficacy with the number needed to treat (NNT) to
      prevent clinical endpoints. Mortality and cirrhosis-related morbidity were
      assessed in an international multicentre cohort of consecutively treated patients
      with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical
      disease progression (any cirrhosis-related event or death) in one patient was
      determined with the adjusted (event-free) survival among patients without SVR and
      adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of
      8.3 (IQR 6.2-11.1) years. Fifty-nine (24%) patients attained SVR. Among patients
      without SVR, the adjusted 5-year survival and event-free survival were 94.4% and
      80.0%, respectively. SVR was associated with reduced all-cause mortality (HR
      0.15, 95% CI 0.05-0.48, P = 0.002) and clinical disease progression (HR 0.16, 95%
      CI 0.07-0.36, P < 0.001). The NNT to prevent one death in 5 years declined from
      1052 (95% CI 937-1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54-101)
      at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected
      with triple therapy, the estimated NNT was 43 (95% CI 38-71). The NNT to prevent
      clinical disease progression in one patient in 5 years was 302 (95% CI 271-407),
      18 (95% CI 16-24) and 13 (95% CI 11-17) at 2%, 35% and 50% SVR, respectively. In
      conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with
      HCV genotype 1 has declined enormously with the improvement of antiviral therapy.

PMID- 24118178
TI  - Update on treatment options for spinal brucellosis.
AB  - We evaluated the efficacy and tolerability of antibiotic regimens and optimal
      duration of therapy in complicated and uncomplicated forms of spinal brucellosis.
      This is a multicentre, retrospective and comparative study involving a total of
      293 patients with spinal brucellosis from 19 health institutions. Comparison of
      complicated and uncomplicated spinal brucellosis was statistically analysed.
      Complicated spinal brucellosis was diagnosed in 78 (26.6%) of our patients.
      Clinical presentation was found to be significantly more acute, with fever and
      weight loss, in patients in the complicated group. They had significantly higher
      leukocyte and platelet counts, erythrocyte sedimentation rates and C-reactive
      protein levels, and lower haemoglobulin levels. The involvement of the thoracic
      spine was significantly more frequent in complicated cases. Spondylodiscitis was
      complicated, with paravertebral abscess in 38 (13.0%), prevertebral abscess in 13
      (4.4%), epidural abscess in 30 (10.2%), psoas abscess in 10 (3.4%) and
      radiculitis in 8 (2.7%) patients. The five major combination regimens were:
      doxycycline 200 mg/day, rifampicin 600 mg/day and streptomycin 1 g/day;
      doxycycline 200 mg/day, rifampicin 600 mg/day and gentamicin 5 mg/kg; doxycycline
      200 mg/day and rifampicin 600 mg/day; doxycycline 200 mg/day and streptomycin 1
      g/day; and doxycycline 200 mg/day, rifampicin 600 mg/day and ciprofloxacin 1
      g/day. There were no significant therapeutic differences between these antibiotic
      groups; the results were similar regarding the complicated and uncomplicated
      groups. Patients were mostly treated with doxycycline and rifampicin with or
      without an aminoglycoside. In the former subgroup, complicated cases received
      antibiotics for a longer duration than uncomplicated cases. Early recognition of
      complicated cases is critical in preventing devastating complications.
      Antimicrobial treatment should be prolonged in complicated spinal brucellosis in
      particular. 

PMID- 24118179
TI  - Van Wyk and Grumbach syndrome: two case reports and review of the published work.
AB  - Van Wyk and Grumbach syndrome is characterized by a long-standing history of
      hypothyroidism, high levels of thyroid-stimulating hormone, uni- or bilateral
      ovarian cysts, isosexual precocity and a delayed bone age. All of the features
      can be reversed with treatment of the underlying hypothyroidism. Here, we
      describe two cases of Van Wyk and Grumbach syndrome presenting with bilateral
      multicystic ovaries and enlargement of the pituitary gland. One patient suffered
      from ovarian cyst and hypophysoma resection, the other patient promptly responded
      to L-thyroxine with complete regression of the ovarian cyst and other symptoms. 

PMID- 24118180
TI  - Rural primary care practices and meaningful use of electronic health records: the
      role of Regional Extension Centers.
AB  - PURPOSE: To examine the role of Regional Extension Centers (RECs) in helping
      rural physician practices adopt electronic health records (EHRs) and achieve
      meaningful use. METHODS: Using data from the Office of the National Coordinator
      for Health Information Technology, we conducted a county-level regression
      analysis using ordinary least squares to better understand rural-urban
      differences in REC participation, EHR implementation, and meaningful use,
      controlling for counties' economic conditions. We prepared case studies of 2 RECs
      that are serving a large number of rural practices, based on interviews with key
      individuals at the RECs, their partner organizations, and rural primary care
      practices that received assistance from the RECs. FINDINGS: RECs are largely
      achieving their objective of targeting providers in communities that face
      barriers to EHRs. REC participants are disproportionately rural and more likely
      to come from high poverty and low employment communities. The case study RECs had
      long-standing relationships with rural providers, as well as extensive staff
      expertise in quality improvement and EHR implementation, and employed a variety
      of strategies to successfully assist rural providers. Rural providers report that
      REC assistance was invaluable in helping them implement EHRs and achieve
      meaningful use status. CONCLUSION: Modifying the criteria for Medicare and
      Medicaid EHR incentives could help additional rural providers pay for EHRs. REC
      federal funding is scheduled to end in 2014, but practices that have not yet
      adopted EHRs may need significant, ongoing assistance to receive meaningful use.

PMID- 24118181
TI  - Who's for dinner? High-throughput sequencing reveals bat dietary differentiation
      in a biodiversity hotspot where prey taxonomy is largely undescribed.
AB  - Effective management and conservation of biodiversity requires understanding of
      predator-prey relationships to ensure the continued existence of both predator
      and prey populations. Gathering dietary data from predatory species, such as
      insectivorous bats, often presents logistical challenges, further exacerbated in
      biodiversity hot spots because prey items are highly speciose, yet their taxonomy
      is largely undescribed. We used high-throughput sequencing (HTS) and
      bioinformatic analyses to phylogenetically group DNA sequences into molecular
      operational taxonomic units (MOTUs) to examine predator-prey dynamics of three
      sympatric insectivorous bat species in the biodiversity hotspot of south-western
      Australia. We could only assign between 4% and 20% of MOTUs to known genera or
      species, depending on the method used, underscoring the importance of examining
      dietary diversity irrespective of taxonomic knowledge in areas lacking a
      comprehensive genetic reference database. MOTU analysis confirmed that resource
      partitioning occurred, with dietary divergence positively related to the
      ecomorphological divergence of the three bat species. We predicted that bat
      species' diets would converge during times of high energetic requirements, that
      is, the maternity season for females and the mating season for males. There was
      an interactive effect of season on female, but not male, bat species' diets,
      although small sample sizes may have limited our findings. Contrary to our
      predictions, females of two ecomorphologically similar species showed dietary
      convergence during the mating season rather than the maternity season. HTS-based
      approaches can help elucidate complex predator-prey relationships in highly
      speciose regions, which should facilitate the conservation of biodiversity in
      genetically uncharacterized areas, such as biodiversity hotspots.

PMID- 24118182
TI  - A novel computer-aided method to fabricate a custom one-piece glass fiber dowel
      and-core based on digitized impression and crown preparation data.
AB  - PURPOSE: Fiber-reinforced composite dowels have been widely used for their
      superior biomechanical properties; however, their preformed shape cannot fit
      irregularly shaped root canals. This study aimed to describe a novel computer
      aided method to create a custom-made one-piece dowel-and-core based on the
      digitization of impressions and clinical standard crown preparations. MATERIALS
      AND METHODS: A standard maxillary die stone model containing three prepared teeth
      each (maxillary lateral incisor, canine, premolar) requiring dowel restorations
      was made. It was then mounted on an average value articulator with the mandibular
      stone model to simulate natural occlusion. Impressions for each tooth were
      obtained using vinylpolysiloxane with a sectional dual-arch tray and digitized
      with an optical scanner. The dowel-and-core virtual model was created by slicing
      3D dowel data from impression digitization with core data selected from a
      standard crown preparation database of 107 records collected from clinics and
      digitized. The position of the chosen digital core was manually regulated to
      coordinate with the adjacent teeth to fulfill the crown restorative requirements.
      Based on virtual models, one-piece custom dowel-and-cores for three experimental
      teeth were milled from a glass fiber block with computer-aided manufacturing
      techniques. Furthermore, two patients were treated to evaluate the practicality
      of this new method. RESULTS: The one-piece glass fiber dowel-and-core made for
      experimental teeth fulfilled the clinical requirements for dowel restorations.
      Moreover, two patients were treated to validate the technique. CONCLUSION: This
      novel computer-aided method to create a custom one-piece glass fiber dowel-and
      core proved to be practical and efficient.

PMID- 24118183
TI  - Denonvilliers' space expansion by transperineal injection of hydrogel:
      implications for focal therapy of prostate cancer.
AB  - We developed and assessed a technique of: (i) expanding Denonvilliers' space by
      hydrogel (polyethylene glycol) during focal cryoabation; and (ii) temperature
      mapping to ensure protection of the rectal wall. In a fresh cadaver, 20 cc of
      hydrogel was injected transperineally into Denonvilliers' space under transrectal
      ultrasound guidance. Successful expansion of Denonvilliers' space was achieved
      with a range of 9-11 mm thickness covering the entire posterior prostate surface.
      Two freeze-thaw cycles were used to expand the iceball reaching the rectal wall
      as an end-point. Intraoperative transrectal ultrasound monitoring and temperature
      mapping in Denonvilliers' space by multiple thermocouples documented real-time
      iceball expansion up to 10 mm beyond the prostate, and safety in protecting the
      rectal wall from thermal injury. The lowest temperatures of the thermocouples
      with a distance of 0 mm, 5 mm and 10 mm from the prostate were: -35 degrees C, 
      18 degrees C and 0 degrees C (P < 0.001), respectively. In gross and microscopic
      examination, the hydrogel mass measured 11 * 40 * 34 mm, which was identical to
      the intraoperative transrectal ultrasound measurements, there was no infiltration
      of the hydrogel into the rectal wall or prostate and no injury to the pelvic
      organs. In conclusion, the expansion of Denonvilliers' space by transperineal
      injection of hydrogel is feasible and a promising technique to facilitate energy
      based focal therapy of prostate cancer.

PMID- 24118185
TI  - Effect of oxytocin, IBMX and dbcAMP on rabbit ovarian follicles.
AB  - Oxytocin (OT) and protein kinase A (PKA), a possible intracellular mediator of
      hormone action in the ovary, can be potent activators of ovarian functions and
      fertility. Nevertheless, action of OT on ovarian follicle atresia has not been
      studied yet. Only single administration of PKA activators [3-isobutyl-1-methyl
      xanthine (IBMX) and dibutyryl cyclic adenosine monophosphate (dbcAMP)] on ovarian
      follicle atresia was studied previously. The aim of this study was to examine the
      effect of OT (single treatment per one reproductive cycle, multiple treatments
      for three cycles), IBMX and dbcAMP (multiple treatments) on folliculogenesis and
      follicular atresia in rabbit. The ovarian cycle in control females was induced
      only by gonadotropins. Experimental females received co-administration of
      gonadotropins with OT, IBMX or dbcAMP (at 50 MUg/female). All females were
      artificially inseminated. Single-treated females were euthanized after 18-19 h.
      Multiple-treated females were euthanized after the third reproductive cycle.
      Histological sections of the ovaries were prepared and evaluated by a light
      microscopy. The follicles were divided into four classes according to the
      structure of granulosa and theca cells as follows: none or small atresia, cystic
      atresia, obliterative atresia and atresia associated with luteinization. The
      ovaries from the control and experimental females, treated during one
      reproductive cycle or three cycles, were compared. Single OT co-administration
      increased proportion of follicles with atresia associated with luteinization, but
      not other types of atresia. No influence of multiple OT co-administration on
      follicular atresia was recorded. Multiple IBMX and dbcAMP co-administration
      decreased the proportion of atretic follicles and increased the proportion of
      healthy follicles without atresia. 

PMID- 24118184
TI  - The development of a normalization method for comparing nerve regeneration
      effectiveness among different graft types.
AB  - The inability to compare directly different nerve grafts has been a significant
      factor hindering the advance of nerve graft development. Due to the abundance of
      variables that exist in nerve graft construction and multiple assessment types,
      there has been limited success in comparing nerve graft effectiveness among
      experiments. Using mathematical techniques on nerve conduction velocity (NCV)
      autograft data, a normalization function was empirically derived that normalizes
      differences in gap lengths. Further analysis allowed for the development of the
      relative regeneration ratio (RRR). The RRR function allows researchers to
      directly compare nerve graft results based on the NCV data from their respective
      studies as long as the data was collected at the same post-operation time. This
      function also allows for comparisons between grafts tested at different gap
      lengths. Initial testing of this RRR function provided confidence that the
      function is accurate for a continuum of gap lengths and different nerve graft
      types. 

PMID- 24118186
TI  - How pain arises in Parkinson's disease?
AB  - In recent years, increasing attention has centred on pain in Parkinson's disease
      (PD). Pain in PD is heterogeneous in quality and body distribution. To clarify
      how the various pain types relate to PD and to propose plausible treatment
      strategies, in this paper we reviewed psychophysical, neurophysiological and
      imaging data reported in parkinsonian patients with and without pain. Most
      available evidence supports abnormal central nociceptive input processing that
      probably reflects an impairment in the lateral and medial pain pathways. Changes
      in central pain processing probably underlie all the different pain types and
      also intervene in patients with PD without pain. Thus, altered pain processing
      might predispose patients with PD to spontaneous pain that is variable in
      quality. These background pain-processing abnormalities may interact with
      additional factors (such as contractures secondary to marked
      rigidity/bradykinesia, dystonia and medical conditions associated with painful
      symptoms), thus causing pain to manifest itself clinically in various ways and
      providing candidate targets for pain treatment in PD. 

PMID- 24118187
TI  - Endoscopic ultrasonography-guided trans-Roux limb drainage of pancreatic duct to
      prevent pancreatitis as a result of percutaneous metallic stent placement for
      malignant biliary stricture.

PMID- 24118188
TI  - Management and diagnostic guidelines for fungal diseases in infectious diseases
      and clinical microbiology: critical appraisal.
AB  - Invasive fungal infections (IFIs) are life-threatening conditions that require
      rapid diagnostic and optimal management to mitigate their high morbidity and
      mortality rate. They are also associated with a high economic burden, owing to
      prolonged hospitalization, the need for intensive supportive care, and the
      consumption of costly new antifungal agents. To address these issues, several
      international organizations have proposed guidelines for the management of IFIs.
      The consistency and reliability of these guidelines have rarely been assessed.
      This article is a review of the differences between the recommendations of the
      Infectious Diseases Society of America, the European Conference on Infection in
      Leukaemia, and the European Society of Clinical Microbiology and Infectious
      Diseases, and will focus on targeted treatment and diagnostic procedures.
      Although the conclusions of the three groups of experts are in many points
      similar we outlined some important differences in the methodology and conclusions
      of ESCMID. The use of these guidelines has the potential to enhance the
      management of fungal infections but is probably currently suboptimal. 

PMID- 24118189
TI  - The association between bone mineral density and periodontitis in Korean adults
      (KNHANES 2008-2010).
AB  - OBJECTIVES: This study investigated the association between bone mineral density
      (BMD) and periodontitis in a representative sample of Korean adults. MATERIAL AND
      METHODS: Of 36 188 individuals who participated in the Korea National Health and
      Nutrition Examination Survey in 2008, 2009, and 2010, 9977 participants aged >=40
      years were included in this cross-sectional study. The associations of BMD of
      lumbar spine, total femur, and femoral neck with periodontitis were investigated
      using logistic regression analysis. Additionally, dose-response relationships
      with BMD divided into quintiles and the association between osteoporosis and
      periodontitis were investigated. RESULTS: With the set of Community Periodontal
      Index (CPI) >= 3 as a dependent variable, logistic regression analysis revealed
      that a decrease of BMD was significantly associated with higher odds of
      periodontitis [range of adjusted odds ratios (AORs); 1.15-1.20, P < 0.001 for all
      BMD sites]. Similarly, these associations were also found in the CPI 4 model.
      With regard to dose-response relations, the lower the BMD quintile, the higher
      the AORs appeared with statistical significance in the CPI >= 3 model. (P for
      trend < 0.001) Participants with osteoporosis had 2.26 and 1.91 times higher odds
      for CPI >= 3 and CPI 4, respectively, than those with normal BMD, indicating a
      significant association between the two diseases. CONCLUSIONS: Our results
      suggest that BMD is significantly associated with periodontitis.

PMID- 24118190
TI  - Incidence of fatal food anaphylaxis in people with food allergy: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of
      fatal food anaphylaxis is not known. The aim of this study was to estimate the
      incidence of fatal food anaphylaxis for people with food allergy and relate this
      to other mortality risks in the general population. METHODS: We undertook a
      systematic review and meta-analysis, using the generic inverse variance method.
      Two authors selected studies by consensus, independently extracted data and
      assessed the quality of included studies using the Newcastle-Ottawa assessment
      scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS or
      AMED, between January 1946 and September 2012, and recent conference abstracts.
      We included registries, databases or cohort studies which described the number of
      fatal food anaphylaxis cases in a defined population and time period and applied
      an assumed population prevalence rate of food allergy. RESULTS: We included data
      from 13 studies describing 240 fatal food anaphylaxis episodes over an estimated
      165 million food-allergic person-years. Study quality was mixed, and there was
      high heterogeneity between study results, possibly due to variation in food
      allergy prevalence and data collection methods. In food-allergic people, fatal
      food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI
      0.94, 3.45; range 0.63, 6.68). In sensitivity analysis with different estimated
      food allergy prevalence, the incidence varied from 1.35 to 2.71 per million
      person-years. At age 0-19, the incidence rate is 3.25 (1.73, 6.10; range 0.94,
      15.75; sensitivity analysis 1.18-6.13). The incidence of fatal food anaphylaxis
      in food-allergic people is lower than accidental death in the general European
      population. CONCLUSION: Fatal food anaphylaxis for a food-allergic person is
      rarer than accidental death in the general population.

PMID- 24118192
TI  - Acral myxoinflammatory fibroblastic sarcoma successfully treated using Mohs
      micrographic surgery.

PMID- 24118191
TI  - Gap junction networks can generate both ripple-like and fast ripple-like
      oscillations.
AB  - Fast ripples (FRs) are network oscillations, defined variously as having
      frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to
      indicate a propensity of cortical tissue to originate seizures. Here, we
      demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human
      cortical tissue in vitro, and present a network model that could explain FRs
      themselves, and their relation to 'ordinary' (slower) ripples. We performed
      network simulations with model pyramidal neurons, having axons electrically
      coupled. Ripples (< 250 Hz) were favored when conduction of action potentials,
      axon to axon, was reliable. Whereas ripple population activity was periodic,
      firing of individual axons varied in relative phase. A switch from ripples to FRs
      took place when an ectopic spike occurred in a cell coupled to another cell,
      itself multiply coupled to others. Propagation could then start in one direction
      only, a condition suitable for re-entry. The resulting oscillations were > 250
      Hz, were sustained or interrupted, and had little jitter in the firing of
      individual axons. The form of model FR was similar to spontaneously occurring FRs
      in excised human epileptic tissue. In vitro, FRs were suppressed by a gap
      junction blocker. Our data suggest that a given network can produce ripples, FRs,
      or both, via gap junctions, and that FRs are favored by clusters of axonal gap
      junctions. If axonal gap junctions indeed occur in epileptic tissue, and are
      mediated by connexin 26 (recently shown to mediate coupling between immature
      neocortical pyramidal cells), then this prediction is testable.

PMID- 24118193
TI  - Is cannabis neurotoxic for the healthy brain? A meta-analytical review of
      structural brain alterations in non-psychotic users.
AB  - AIMS: Despite growing research in the field of cannabis imaging, mostly in those
      with a psychotic illness, the possible neurotoxic effects of smoked cannabis on
      the healthy brain have yet to be fully understood. There appears to be a need to
      evaluate the existing imaging data on the neuroanatomical effects of cannabis use
      on non-psychotic populations. METHODS: We conducted a meta-analytical review to
      estimate the putative neurotoxic effect of cannabis in non-psychotic subjects who
      were using or not using cannabis. We specifically tested the hypothesis that
      cannabis use can alter grey and white matter in non-psychotic subjects. RESULTS:
      Our systematic literature search uncovered 14 studies meeting the inclusion
      criteria for the meta-analysis. The overall database comprised 362 users and 365
      non-users. At the level of the individual studies there is limited and
      contrasting evidence supporting a cannabis-related alteration on the white and
      grey matter structures of non-psychotic cannabis users. However, our meta
      analysis showed a consistent smaller hippocampus in users as compared to non
      users. Heterogeneity across study designs, image acquisition, small sample sizes
      and limited availability of regions of interest to be included in the meta
      analysis may undermine the core findings of this study. CONCLUSIONS: Our results
      suggest that in the healthy brain, chronic and long-term cannabis exposure may
      exert significant effects in brain areas enriched with cannabinoid receptors,
      such as the hippocampus, which could be related to a neurotoxic action.

PMID- 24118194
TI  - Allergen immunotherapy decreases LPS-induced NF-kappaB activation in neutrophils
      from allergic patients.
AB  - BACKGROUND: Allergen-specific immunotherapy (IT) is widely used to treat allergic
      diseases. The molecular mechanisms have not been clarified yet completely. The
      present work was undertaken to analyze the effect of IT in the activation of NF
      kappaB. METHODS: Neutrophils from 15 pollen-allergic IT-treated patients, 10
      untreated pollen-allergic patients, and 10 healthy donors were in vitro
      stimulated with LPS. NF-kappaB activation (p65/p52) was measured in their nuclear
      extracts by enzyme-linked immunosorbent assay (ELISA). IkappaBalpha
      phosphorylation, NF-kappaB-repressing factor (NRF) activation, and thromboxane A2
      (TXA2 ) and Interleukin-8 (IL-8) release were measured by ELISA. RESULTS: There
      was a positive correlation between the score of symptoms and NF-kappaB activation
      in human neutrophils. IT significantly decreased NF-kappaB activation levels in
      neutrophils compared with neutrophils from untreated patients. IkappaBalpha
      phosphorylation and NRF activation levels were, respectively, significantly lower
      and higher in neutrophils from IT-treated patients than from untreated patients.
      IL-8 and TXA2 release were significantly lower in neutrophils from IT-treated
      patients than from untreated patients. CONCLUSIONS: IT positive effects are at
      least in part mediated by the negative regulation of NF-kappaB activation in
      human neutrophils. These observations represent a novel view of neutrophils as
      possible cell target to treat IgE-dependent diseases through NF-kappaB
      downmodulation.

PMID- 24118195
TI  - Higher anti-tumour efficacy of platinum(IV) complex LA-12 is associated with its
      ability to bypass M-phase entry block induced in oxaliplatin-treated human colon
      cancer cells.
AB  - OBJECTIVES: Therapeutic potential of conventionally used platinum-based drugs in
      treatment of colorectal tumours has been limited due to high incidence of tumour
      resistance to them and to their severe side effects. This evokes a search for
      more suitable anti-cancer drugs. We have compared ability of oxaliplatin and a
      novel platinum(IV) complex, LA-12, to modulate the cell cycle and induce
      apoptosis in human colon adenocarcinoma HCT116 wt and p53/p21 null cells, and
      have investigated molecular mechanisms involved. MATERIALS AND METHODS: Cell
      cycle-related changes were analysed by flow cytometry
      (bromodeoxyuridine/propidium iodide staining, histone H3 phosphorylation).
      Apoptosis was detected using flow cytometry (assays monitoring caspase activity)
      and fluorescence microscopy (nuclear morphology). Changes in levels of
      genes/proteins involved in cell cycle and apoptosis regulation were examined by
      RT-PCR and western blotting. RESULTS: Our results highlight the outstanding
      ability of LA-12 to induce effective elimination of colon cancer cells
      independently of p53/p21, and in significantly lower doses compared to
      oxaliplatin. While oxaliplatin induced p53- and p21-dependent G2 -phase arrest
      associated with downregulation of cyclin B1 and Cdk1, LA-12 allowed cells to
      enter M-phase of the cell cycle regardless of p53/p21 status. CONCLUSIONS: Higher
      malignant cell toxicity and ability to bypass cell cycle arrest important for the
      cell damage repair suggest LA-12 to be a more effective candidate for elimination
      of colon tumours from a variety of genetic backgrounds, compared with
      oxaliplatin.

PMID- 24118196
TI  - Role of tissue expanders in patients with loss of abdominal domain awaiting
      intestinal transplantation.
AB  - Abdominal closure is a complex surgical problem in intestinal transplant
      recipients with loss of abdominal domain, as graft exposure results in profound
      morbidity. Although intraoperative coverage techniques have been described, this
      is the first report of preoperative abdominal wall augmentation using tissue
      expanders in patients awaiting intestinal transplantation. We report on five
      patients who received a total of twelve tissue expanders as a means to increase
      abdominal surface area. Each patient had a compromised abdominal wall (multiple
      prior operations, enterocutaneous fistulae, subcutaneous abscesses, stomas) with
      loss of domain and was identified as high risk for an open abdomen post
      transplant. Cross-sectional imaging and dimensional analysis were performed to
      quantify the effect of the expanders on total abdominal and intraperitoneal
      cavity volumes. The overall mean increase in total abdominal volume was 958 cm(3)
      with a mean expander volume of 896.5 cc. Two expanders were removed in the first
      patient due to infection, but after protocol modification, there were no further
      infections. Three patients eventually underwent small bowel transplantation with
      complete graft coverage. In our preliminary experience, abdominal tissue expander
      placement is a safe, feasible, and well-tolerated method to increase subcutaneous
      domain and facilitate graft coverage in patients undergoing intestinal
      transplantation.

PMID- 24118197
TI  - Quantitative magnetic resonance imaging analysis of the relationship between
      contact force and left atrial scar formation after catheter ablation of atrial
      fibrillation.
AB  - BACKGROUND: Catheter contact force (CF) is an important determinant of
      radiofrequency (RF) lesion quality during pulmonary vein isolation (PVI). Late
      gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows good
      visualization of ablation lesions. OBJECTIVE: This study describes a new
      technique to examine the relationship between CF during RF delivery and LGE
      signal intensity (SI) following PVI. METHODS: Six patients underwent PVI for
      paroxysmal AF using a CF-sensing catheter and following preprocedural MRI. During
      ablation, CF-time integral (FTI) and position was documented for each RF
      application. All patients underwent repeat LGE MRI 3 months later. The LGE SIs
      were projected onto a MRI-derived 3-dimensional left atrial (LA) shell and a CF
      map was generated on the same shell. The entire LA surface was divided into 5
      mm(2) segments. Force and LGE maps were fused and compared for each 5 mm(2) zone.
      An effective lesion was defined when MRI-defined scar occupied >90% of a 5 mm(2)
      analysis zone. RESULTS: Acute PVI was achieved in 100%. Two hundred sixty-eight
      RF lesions were tagged on the LA shells and given a lesion-specific FTI.
      Increasing FTI correlated with increased LGE SI, which was greater when the FTI
      was > 1,200 gs. Below an FTI of 1,200 gs, an increment in the FTI resulted in
      only a small increment in scar, whereas above 1,200 gs an increment in the FTI
      resulted in a large change of scar. CONCLUSION: There is a correlation between
      FTI and LGE SI in MRI following AF ablation. Real-time FTI maps are feasible and
      may prevent inadequate lesion formation.

PMID- 24118198
TI  - Clinical and angiographic outcomes with everolimus eluting stents for the
      treatment of cardiac allograft vasculopathy.
AB  - OBJECTIVES: This study aimed to examine clinical efficacy, safety, and
      intermediate clinical outcomes with everolimus-eluting stents (EESs) in patients
      with transplant coronary artery disease (TCAD). BACKGROUND: TCAD is a major cause
      of mortality in patients following orthotopic heart transplantation (OHT).
      Systemic everolimus in OHT patients has been shown to reduce TCAD. The safety and
      efficacy of an EES, the Xience V, have not been evaluated in this population.
      METHODS: Patients post-OHT with hemodynamically significant CAD who underwent
      percutaneous coronary intervention (PCI) with EES were included. Participants
      were maintained on dual antiplatelet therapy for 1-year post-PCI. We examined
      procedural success, in-hospital and 1-year mortality, stent thrombosis,
      angiographic restenosis, and myocardial infarction rates. All patients had follow
      up angiography 1-year after PCI. Target vessel revascularization (TVR), target
      lesion revascularization (TLR), in-segment restenosis, target vessel failure
      (TVF), and lumen late loss were noted. RESULTS: PCI was performed in 34 de novo
      lesions in 21 patients, and 40 EES were placed. Procedural success rate was 100%.
      Average stent was 16.5 +/- 5.1 mm long and 3.0 +/- 0.6 mm in diameter. All
      patients had angiographic follow-up (409 +/- 201 days). There was no stent
      thrombosis, deaths, or myocardial infarctions during follow-up. Two patients had
      focal in-stent restenosis. TLR rate was 5.9% (2/34), and TVR rate was 11.1%
      (3/27). Quantitative coronary angiography (QCA) showed stenosis diameter to be
      19.98 +/- 17.57%. CONCLUSIONS: Use of an EES is associated with a low incidence
      of TVR and TLR in patients with TCAD. Further studies are needed to determine
      whether PCI with EES changes long-term outcomes.

PMID- 24118199
TI  - The role of learning by a predator, Rivulus hartii, in the rare-morph survival
      advantage in guppies.
AB  - Negative frequency-dependent selection (NFDS), where rare types are favoured by
      selection, can maintain diversity. However, the ecological processes that mediate
      NFDS are often not known. Male guppies (Poecilia reticulata) exhibit extreme
      diversity of colour patterning and, in a previous field experiment, rare morphs
      had a survival advantage. Here, we test the hypothesis that predators impose NFDS
      because they are efficient at capturing familiar prey morphs, but are less
      efficient at capturing unfamiliar morphs. Over a series of trials, we presented
      Rivulus hartii, a natural predator of guppies, with male guppies with the same
      colour patterning (A trials); then, for a second series of trials, we presented
      the rivulus with guppies with a new colour pattern (B trials). The success of
      rivulus at capturing guppies on the first attack increased over successive A
      trials. First attack success decreased significantly for the early B trials, and
      then increased during successive B trials, eventually reaching the same level as
      in the best A trials. This experiment demonstrates that learning, perhaps through
      long-term search image formation, plays a role in predation success on familiar
      vs. unfamiliar prey morphs. These results support the hypothesis that predator
      learning contributes to the maintenance of the extreme male guppy polymorphism
      seen in nature. 

PMID- 24118200
TI  - Features governing symbiont persistence in the squid-vibrio association.
AB  - Experimental studies of the interaction between host and symbiont in a maturing
      symbiotic organ have presented a challenge for most animal-bacterial
      associations. Advances in the rearing of the host squid Euprymna scolopes have
      enabled us to explore the relationship between a defect in symbiont light
      production and late-stage development (e.g. symbiont persistence and tissue
      morphogenesis) by experimental colonization with specific strains of the symbiont
      Vibrio fischeri. During the first 4 weeks postinoculation of juvenile squid, the
      population of wild-type V. fischeri increased 100-fold; in contrast, a strain
      defective in light production (Deltalux) colonized normally the first day, but
      exhibited an exponential decline to undetectable levels over subsequent weeks. Co
      colonization of organs by both strains affected neither the trajectory of
      colonization by wild type nor the decline of Deltalux levels. Uninfected animals
      retained the ability to be colonized for at least 2 weeks posthatch. However,
      once colonized by the wild-type strain for 5 days, a subsequent experimentally
      induced loss of the symbionts could not be followed by a successful
      recolonization, indicating the host's entry into a refractory state. However,
      animals colonized by the Deltalux before the loss of their symbionts were
      receptive to recolonization. Analyses of animals colonized with either a wild
      type or a Deltalux strain revealed slight, if any, differences in the
      developmental regression of the ciliated light-organ tissues that facilitate the
      colonization process. Thus, some other feature(s) of the Deltalux strain's defect
      also may be responsible for its inability to persist, and its failure to induce a
      refractory state in the host.

PMID- 24118201
TI  - Cell-wall-inhibiting antibiotic combinations with activity against multidrug
      resistant Klebsiella pneumoniae and Escherichia coli.
AB  - The increasing prevalence of hospital and community-acquired infections caused by
      multidrug-resistant (MDR) bacterial pathogens is rapidly limiting the options for
      effective antibiotic therapy. Systematic studies on combinations of already
      available antibiotics that could provide an effective treatment against MDR
      bacteria are needed. We tested combinations of antibiotics that target one
      important physiological function (peptidoglycan synthesis) at several steps, and
      studied Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) for which
      multidrug resistance associated with ESBL-producing plasmids has become a major
      problem. To measure the effectiveness of antibiotics alone and in combination, we
      used checkerboard assays, static antibiotic concentration time-kill assays, and
      an improved in-vitro kinetic model that simulates human pharmacokinetics of
      multiple simultaneously administered antibiotics. The target strains included an
      MDR K. pneumoniae isolate responsible for a recent major hospital outbreak. A
      double combination (fosfomycin and aztreonam) and a triple combination
      (fosfomycin, aztreonam and mecillinam) were both highly effective in reducing
      bacterial populations in all assays, including the in vitro kinetic model. These
      combinations were effective even though each of the MDR strains was resistant to
      aztreonam alone. Our results provide an initial validation of the potential
      usefulness of a combination of antibiotics targeting peptidoglycan synthesis in
      the treatment of MDR Gram-negative bacteria. We suggest that a combination of
      fosfomycin with aztreonam could become a useful treatment option for such
      infections and should be further studied.

PMID- 24118202
TI  - Transition from failing dentition to full-arch fixed implant-supported prosthesis
      with a staged approach using removable partial dentures: a case series.
AB  - The present retrospective case series is aimed at evaluating a staged approach
      using a removable partial denture (RPD) as an interim prosthesis in treatment to
      correct a failing dentition until such time as a full-arch fixed implant
      supported prosthesis may be inserted. Eight patients, who had undergone maxillary
      full-arch rehabilitation with dental implants due to poor prognosis of their
      dentitions, were analyzed. All treatment included initial periodontal therapy and
      a strategic order of extraction of hopeless teeth. An RPD supported by selected
      teeth rehabilitated the compromised arch during implant osseointegration. These
      remaining teeth were extracted prior to definitive prosthesis delivery.
      Advantages and drawbacks of this technique were also recorded for the cases
      presented. Among the advantages provided by the staged approach are simplicity of
      fabrication, low cost, and ease of insertion. Additionally, RPD tooth support
      prevented contact between the interim prosthesis and healing abutments, promoting
      implant osseointegration. The main drawbacks were interference with speech and
      limited esthetic results. Implant survival rate was 100% within a follow-up of at
      least 1 year. The use of RPDs as interim prostheses allowed for the
      accomplishment of the analyzed rehabilitation treatments. It is a simple
      treatment alternative for patients with a low smile line. 

PMID- 24118203
TI  - Application of ripple mapping with an electroanatomic mapping system for
      diagnosis of atrial tachycardias.
AB  - BACKGROUND: Three-dimensional (3D) mapping is often used to guide ablation in
      atrial tachycardia (AT), but maps can be susceptible to annotation and
      interpolation errors. Ripple Mapping (RM) is a technique that displays
      electrogram time-voltage data simultaneously as dynamic bars on the surface shell
      to overcome these limitations. OBJECTIVES: We hypothesized that RM would be
      superior to established 3D activation mapping. METHODS: CARTO-XPTM maps of ATs
      were collected without any manual annotation and studied on a CARTO-based offline
      RM system. Paired unannotated CARTO-XP and Ripple Maps were presented to
      experienced CARTO users with limited RM training. These assessors were allowed to
      annotate the CARTO-XP maps, but were blinded to conventional EP data. RESULTS:
      CARTO-XP maps of AT (10 patients) were studied in RM format and the diagnosis was
      confirmed by entrainment in all cases and with termination of tachycardia in 9/10
      cases. Blinded assessors (n = 11) reached the correct diagnosis using RM in 35/44
      (80%) compared to 22/44 (50%) using CARTO-XP (P = 0.029). The time to the correct
      diagnosis was also shorter with RM (136 seconds vs. 212 seconds; P = 0.022). The
      causes of diagnostic errors using RM (insufficient point density, particularly in
      low-voltage areas, and the operator not assessing all available views) were
      overcome with an improved MatLab version showing both scar and dynamic bars on
      the same shell. CONCLUSION: RM does not need any manual annotation of local
      activation time and enables rapid diagnosis of AT with higher diagnostic accuracy
      than conventional 3D activation mapping.

PMID- 24118204
TI  - Endodermal sinus tumor of vagina posing a diagnostic challenge and managed by
      chemotherapy and novel posterior sagittal surgical approach: lessons learned.
AB  - Vaginal germ cell tumor (GCT) is a rare gynecological malignancy with no more
      than 100 reported cases in the international medical literature. It is an
      unusual, but an important, cause of premenarchal vaginal bleeding in a child.
      This article describes a 2-year-old child with vaginal GCT, initially
      misdiagnosed as rhabdomyosarcoma (on imprint smear cytology) and then as clear
      cell adenocarcinoma. The authors highlight the salient differentiating clinical,
      radiological and histological features to prevent misdiagnosis in future. The
      report emphasizes the need for increased awareness and screening for vaginal GCT
      by estimation of serum alpha-fetoprotein levels, in all patients with
      premenarchal vaginal bleeds, to prevent inadvertent operative interventions. 

PMID- 24118205
TI  - Transesophageal echocardiography guided patent ductus arteriosus occlusion with a
      duct occluder.
AB  - BACKGROUND: Angiography and fluoroscopy are the standard methods to guide
      transcatheter occlusion of patent ductus arteriosus (PDA). The use of iodinated
      contrast agents and radiation exposure pose risks of animals and staff.
      OBJECTIVES: To assess feasibility of transesophageal echocardiography (TEE) for
      device size selection and procedure monitoring for PDA occlusion with a duct
      occluder (DO) without the use of angiography. ANIMALS: Eighty client-owned dogs
      with left-to-right PDA. METHODS: Prospective study. Dogs with left-to-right PDA
      undergoing transcatheter occlusion were included. Procedures were performed
      without angiography and device size selection was based on TEE measurements.
      Procedures were monitored with simultaneous TEE and fluoroscopy and both methods
      were compared. Visualization of the ductus and dimensions obtained by TEE and
      transthoracic echocardiography (TTE) were compared. RESULTS: Complete PDA
      occlusion was achieved in 79/80 cases. TEE was consistently superior to TTE for
      PDA visualization and the latter showed higher values for ductal dimensions when
      compared to the former. TEE provided adequate procedure monitoring in 73 cases
      (91%). Fluoroscopy exposure time (2.77 +/- 1.2 minutes (mean, SD)) was lower than
      previously reported for the same procedure. CONCLUSIONS AND CLINICAL IMPORTANCE:
      TEE is a useful and efficient tool for device size selection and can be used for
      procedure monitoring in most cases. Fluoroscopy exposure time can be reduced and
      the use of contrast agents can be avoided. However, fluoroscopy is required in a
      minority of cases when TEE monitoring is not feasible or incomplete and should be
      available for this procedure.

PMID- 24118206
TI  - Occipital nerve stimulation in fibromyalgia: a double-blind placebo-controlled
      pilot study with a six-month follow-up.
AB  - OBJECTIVE: The goal of this study is to evaluate the effectiveness of occipital
      nerve stimulation (ONS) as a surgical treatment for fibromyalgia in a placebo
      controlled design. MATERIALS AND METHODS: Eleven patients were selected based on
      the American College of Rheumatology-90 criteria and implanted with an occipital
      nerve trial-lead stimulator. Baseline scores for pain, mood, and fatigue were
      acquired, and patients were randomized in a ten-week double-blinded crossover
      design with placebo and effective subsensory threshold stimulation (no
      paresthesias). After finalizing the trial, nine patients were implanted
      permanently; evaluation was performed prior to surgery and at six months after
      surgery for pain, fatigue, and mood of the number of trigger points and overall
      morbidity. RESULTS: Significant results were found during the trial for a
      decrease in pain intensity (39.74%) on visual analogue scale (VAS; p < 0.001) and
      pain catastrophizing scale (PCS) during effective stimulation. A total of 9/11
      patients responded to trial treatment; however, in two patients, this might be a
      placebo effect, recognizable due to the study design. Six months after permanent
      implantation, pain intensity remained decreased (44.01%) on VAS (p < 0.05).
      Besides the VAS, significant changes were noted for PCS, fatigue (modified
      fatigue impact scale), the number of trigger points, and overall morbidity
      (fibromyalgia impact questionnaire). There were no serious adverse events.
      CONCLUSIONS: Our data strongly suggest that ONS is beneficial in the treatment of
      fibromyalgia. The beneficial effects are stable at six months after permanent
      implantation. Subsensory threshold stimulation is feasible in designing a placebo
      controlled trial.

PMID- 24118207
TI  - Oncogenic BRAF signalling increases Mcl-1 expression in cutaneous metastatic
      melanoma.
AB  - The Bcl-2 family member Mcl-1 is essential for melanoma survival; however, the
      influence of oncogenic BRAF signalling remains elusive. In this study, Mcl-1
      splice variant expression was determined in a panel of melanoma cell lines in
      relation to BRAF mutational status. Mcl-1L mRNA expression was increased in
      melanoma cells compared with primary melanocytes with significantly increased
      mRNA and protein expression observed in BRAF(V600E) mutant melanoma cells.
      Although no change in Mcl-1S mRNA was observed, Mcl-1S protein expression also
      increased in BRAF mutant melanoma cells. Additionally, while over-expression of
      mutant BRAF(V600E) increased both Mcl-1L and Mcl-1S expression, inhibition of
      hyperactive BRAF signalling resulted in decreased Mcl-1L expression. These
      studies suggest that the regulation of Mcl-1 expression by BRAF signalling is
      increased by oncogenic activation of BRAF, revealing a mechanism of apoptotic
      resistance which may be overcome by the use of more specifically targeted Mcl-1
      inhibitors. 

PMID- 24118208
TI  - Lipid profile and thyroid hormone concentrations in children with epilepsy
      treated with oxcarbazepine monotherapy: a prospective long-term study.
AB  - BACKGROUND AND PURPOSE: To evaluate prospectively the changes and possible
      associations in lipid and thyroid profiles in children treated with oxcarbazepine
      (OXC) monotherapy. METHODS: Serum total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),
      triglycerides (TGs), lipoprotein (a) [Lp(a)], free thyroxine (FT4), free
      triiodothyronine (FT3), thyrotropin (TSH) and gamma-glutamyltransferase (GGT)
      concentrations were measured in 23 children with epilepsy, before and at 8 and 18
      months of OXC monotherapy. RESULTS: Total cholesterol was significantly increased
      at 8 months (P = 0.033), whereas LDL-C was significantly increased at 8 and 18
      months (P < 0.001 and P = 0.004, respectively) of treatment. Lp(a) was
      significantly increased at 8 months (P = 0.042) and borderline significantly
      increased at 18 months (P = 0.050) of treatment. FT4 was significantly decreased
      at 8 and 18 months (P < 0.001 and P = 0.002, respectively), and TSH levels were
      significantly increased at 8 and 18 months (P = 0.002 and P = 0.001,
      respectively) of OXC monotherapy. GGT levels were significantly increased at 8
      and 18 months (P < 0.001) of treatment. There were no significant alterations in
      HDL-C, TGs and FT3 levels during the study. Significant positive correlations
      were found between GGT and LDL-C levels at 8 (r = 0.468, P = 0.024) and 18 months
      (r = 0.498, P = 0.016), and between TSH and TC at 18 months (r = 0.508, P =
      0.013) of treatment. CONCLUSIONS: OXC monotherapy may cause significant and
      persistent alterations in lipid and thyroid profiles in children with epilepsy.
      The increase in LDL-C and TC levels may be associated with liver enzymes
      induction and thyroid dysfunction. Further long-term prospective studies are
      required to confirm these findings and to determine their clinical significance.

PMID- 24118209
TI  - Editorial Comment to Partial nephrectomy versus radical nephrectomy for non
      metastatic pathological T3a renal cell carcinoma: a multi-institutional
      comparative analysis.

PMID- 24118210
TI  - Asexual genome evolution in the apomictic Ranunculus auricomus complex: examining
      the effects of hybridization and mutation accumulation.
AB  - Asexual lineages are thought to be prone to extinction because of deleterious
      mutation accumulation (Muller's ratchet). Here, we analyse genomic effects of
      hybridity, polyploidy and allelic divergence in apomictic plants, and identify
      loci under divergent selection among sexual/apomictic lineages. RNAseq was used
      to sequence the flower-specific transcriptomes of five genotypes of the
      Ranunculus auricomus complex, representing three sexual and two apomictic
      reproductive biotypes. The five sequence libraries were pooled and de novo
      assembly performed, and the resultant assembly was used as a backbone for a
      subsequent alignment of each separate library. High-quality single-nucleotide
      (SNP) and insertion-deletion (indel) polymorphisms were mined from each library.
      Annotated genes for which open reading frames (ORF) could be determined were
      analysed for signatures of divergent versus stabilizing selection. A comparison
      between all genotypes supports the hypothesis of Pleistocene hybrid origin of
      both apomictic genotypes from R. carpaticola and R. cassubicifolius, with
      subsequent allelic divergence of apomictic lineages (Meselson effect). Pairwise
      comparisons of nonsynonymous (dN) to synonymous (dS) substitution rate ratios
      between apomictic and sexual genotypes for 1231 genes demonstrated similar
      distributions for all comparisons, although 324 genes demonstrated outlier (i.e.
      elevated) dN/dS ratios. Gene ontology analyses of these outliers revealed
      significant enrichment of genes associated with reproduction including meiosis
      and gametogenesis, following predictions of divergent selection between sexual
      and apomictic reproduction, although no significant signal of genome-wide
      mutation accumulation could be identified. The results suggest that gene function
      should be considered in order to understand effects of mutation accumulation in
      asexual lineages. 

PMID- 24118211
TI  - Uncommon and rarely reported adverse events of endoscopic retrograde
      cholangiopancreatography.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has become a primary tool
      for the treatment of biliary and pancreatic ductal diseases. It is essential for
      the endoscopist carrying out the ERCP to have a thorough understanding of the
      potential adverse events. Typically, endoscopists are well familiar with common
      adverse events such as post-ERCP pancreatitis, cholangitis, post-sphincterotomy
      bleeding, post-sphincterotomy perforation, and sedation-related cardiopulmonary
      compromises. However, there are other less common adverse events that arecritical
      to promptly recognize in order to provide appropriate therapy and prevent
      disastrous outcomes. This review focuses on the presentation and management of
      the less common and rare adverse events of an ERCP from the perspective of the
      practicing endoscopist. 

PMID- 24118212
TI  - Verification of the in vivo activity of three distinct cis-acting elements within
      the Gata1 gene promoter-proximal enhancer in mice.
AB  - The transcription factor GATA1 is essential for erythroid and megakaryocytic cell
      differentiation. Gata1 hematopoietic regulatory domain (G1HRD) has been shown to
      recapitulate endogenous Gata1 gene expression in transgenic mouse assays in vivo.
      G1HRD contains a promoter-proximal enhancer composed of a GATA-palindrome motif,
      four CP2-binding sites and two CACCC boxes. We prepared transgenic reporter mouse
      lines in which green fluorescent protein and beta-galactosidase expression are
      driven by wild-type G1HRD (as a positive control) and the G1HRD harboring
      mutations within these cis-acting elements (as the experimental conditions),
      respectively. Exploiting this transgenic dual reporter (TDR) assay, we show here
      that in definitive erythropoiesis, G1HRD activity was markedly affected by
      individual mutations in the GATA-palindrome motif and the CACCC boxes. Mutation
      of CP2-binding sites also moderately decreased G1HRD activity. The combined
      mutation of the CP2-binding sites and the GATA-palindrome motif resulted in
      complete loss of G1HRD activity. In contrast, in primitive erythroid cells,
      individual mutations of each element did not affect G1HRD activity; G1HRD
      activity was abolished only when these three mutations were combined. These
      results thus show that all three elements independently and cooperatively
      contribute to G1HRD activity in vivo in definitive erythropoiesis, although these
      are contributing redundantly to primitive erythropoiesis. 

PMID- 24118214
TI  - Developments in the field of allergy in 2012 through the eyes of Clinical &
      Experimental Allergy.
AB  - In 2012, we received 683 submissions and published 20 editorials, 38 reviews, 11
      letters and 128 original articles. This represents an acceptance rate for
      original papers in the range of 20%. About 30% of original papers were triaged
      not to go out to review, either because the editors did not feel they had
      sufficient priority for publication or because the topic did not feel right for
      the readers of the journal. We place great emphasis on obtaining sufficient high
      quality reviews to make our decisions on publication fair and consistent.
      Inevitably, however, there is a degree of luck about what gets published and
      which papers miss out, and we are always happy to receive an appeal on our
      decisions either at the triage stage or after review. This gives us the
      opportunity to revisit the decision and revise it or explain in more detail to
      the authors the basis for the decision. Once again in 2012, we were delighted by
      the quality of the papers submitted and the breadth and depth of research into
      allergic disease that it revealed. The pattern of papers submitted was similar in
      previous years with considerable emphasis on all aspects of asthma and rhinitis.
      We were particularly pleased with our special issue on severe asthma. Elucidating
      mechanisms using either animal models or patients has always been a major theme
      of the journal, and the excellent work in these areas has been summarized by
      Harissios Vliagoftis with a particularly interesting section on early-life events
      guiding the development of allergic disease, which understandably continue to be
      a major theme of research. Magnus Wickman summarized the papers looking at the
      epidemiology of allergic disease including work from birth cohorts, which are an
      increasingly rich source of data on risk factors for allergic disease, and two
      papers on the epidemiology of anaphylaxis. Giovanni Passalacqua discussed the
      papers in the clinical allergy section of the journal, and Adriano Mari who runs
      the excellent Allergome website discussed the papers looking at allergens
      including characterization and the relative usefulness of allergen arrays versus
      single extracts in diagnosis and management. 

PMID- 24118213
TI  - Lentivirus-mediated alpha-melanocyte-stimulating hormone overexpression in the
      hypothalamus decreases diet induced obesity in mice.
AB  - Melanocyte stimulating hormone (MSH) derived from the pro-hormone pro
      opiomelanocortin (POMC) has potent effects on metabolism and feeding that lead to
      reduced body weight in the long-term. To determine the individual roles of POMC
      derived peptides and their sites of action, we created a method for the delivery
      of single MSH peptides using lentiviral vectors and studied the long-term anti
      obesity effects of hypothalamic alpha-MSH overexpression in mice. An alpha-MSH
      lentivirus (LVi-alpha-MSH-EGFP) vector carrying the N'-terminal part of POMC and
      the alpha-MSH sequence was generated and shown to produce bioactive peptide in an
      in vitro melanin synthesis assay. Stereotaxis was used to deliver the LVi-alpha
      MSH-EGFP or control LVi-EGFP vector to the arcuate nucleus (ARC) of the
      hypothalamus of male C57Bl/6N mice fed on a high-fat diet. The effects of 6-week
      treatment on body weight, food intake, glucose tolerance and organ weights were
      determined. Additionally, a 14-day pairfeeding study was conducted to assess
      whether the weight decreasing effect of the LVi-alpha-MSH-EGFP treatment is
      dependent on decreased food intake. The 6-week LVi-alpha-MSH-EGFP treatment
      reduced weight gain (8.4 +/- 0.4 g versus 12.3 +/- 0.6 g; P < 0.05), which was
      statistically significant starting from 1 week after the injections. The weight
      of mesenteric fat was decreased and glucose tolerance was improved compared to
      LVi-EGFP treated mice. Food intake was decreased during the first week in the LVi
      alpha-MSH-EGFP treated mice but subsequently increased to the level of LVi-EGFP
      treated mice. The LVi-EGFP injected control mice gained more weight even when
      pairfed to the level of food intake by LVi-alpha-MSH-EGFP treated mice. We
      demonstrate that gene transfer of alpha-MSH, a single peptide product of POMC,
      into the ARC of the hypothalamus, reduces obesity and improves glucose tolerance,
      and that factors other than decreased food intake also influence the weight
      decreasing effects of alpha-MSH overexpression in the ARC. Furthermore, viral MSH
      vectors delivered stereotaxically provide a novel tool for further exploration of
      chronic site-specific effects of POMC peptides.

PMID- 24118215
TI  - First report of the predominance of clonal complex 398 Staphylococcus aureus
      strains in osteomyelitis complicating diabetic foot ulcers: a national French
      study.
AB  - Staphylococcus aureus is the most common pathogen cultured from diabetic foot
      infection including diabetic foot osteomyelitis. This French multicentre study
      determined the genetic content of S. aureus isolated from 157 consecutive cases
      admitted to 12 diabetic foot centres between 2008 and 2011. We describe for the
      first time the emergence of the CC398 methicillin-susceptible S. aureus clone,
      the main clone in diabetic foot osteomyelitis, and its tropism for bone. This
      clone spreads to humans from an animal source through its intrinsic virulence.
      This adaptation of S. aureus isolates looks to be a worrisome problem and should
      be carefully monitored.

PMID- 24118216
TI  - Three-dimensional orientation of iris in an ocular prosthesis using a customized
      scale.
AB  - The success of an ocular prosthesis depends largely on the correct orientation of
      the iris disk. Various methods have been put forth to achieve this. This article
      emphasizes one such simplified method, wherein a customized scale has been used
      to orient the iris disk mediolaterally, superoinferiorly, and anteroposteriorly
      in an ocular prosthesis. A scleral wax pattern was fabricated. The customized
      scale was used to measure the dimension and orientation of the natural iris.
      These measurements were then transferred to the scleral wax pattern with the
      customized scale. An iris disk was fabricated using black crayon on the scleral
      wax pattern according to the measurements. The scleral wax pattern, including the
      iris disk, was then placed in the eye socket to verify its dimension and
      orientation. A prefabricated iris disk was modified according to the measured
      dimensions and transferred to the final scleral wax pattern. The transfer of
      these dimensions to the definitive prosthesis was achieved successfully,
      ultimately improving the patient's social and psychological well being. 

PMID- 24118217
TI  - Review of mental-health-related stigma in Japan.
AB  - The aim of this study is to understand the nature and characteristics of mental
      health-related stigma among Japanese people. We searched relevant studies in
      English or Japanese published since 2001 using MEDLINE and PsycINFO, and found 19
      studies that examined mental-health-related stigma in Japan. Regarding knowledge
      about mental illness, reviewed studies showed that in the Japanese general
      population, few people think that people can recover from mental disorders.
      Psychosocial factors, including weakness of personality, are often considered the
      cause of mental illness, rather than biological factors. In addition, the
      majority of the general public in Japan keep a greater social distance from
      individuals with mental illness, especially in close personal relationships.
      Schizophrenia is more stigmatized than depression, and its severity increases the
      stigmatizing attitude toward mental illness. The literature also showed an
      association between more direct social contact between health professionals and
      individuals with mental illness and less stigmatization by these professionals.
      Less stigmatization by mental health professionals may be associated with
      accumulation of clinical experience and daily contact with people who have mental
      illness. Stigmatizing attitudes in Japan are stronger than in Taiwan or
      Australia, possibly due to institutionalism, lack of national campaigns to tackle
      stigma, and/or society's valuing of conformity in Japan. Although educational
      programs appear to be effective in reducing mental-health-related stigma, future
      programs in Japan need to address problems regarding institutionalism and offer
      direct social contact with people with mental illness. 

PMID- 24118218
TI  - Consensus recommendations on the aesthetic usage of botulinum toxin type A in
      Asians.
AB  - BACKGROUND: The use of botulinum toxin has rapidly expanded into various
      aesthetic applications. Any guideline representing a consensus for aesthetic
      treatments using botulinum toxin type A (BTA) in Asians has not been published.
      OBJECTIVES: To provide consensus recommendations on common aesthetic problems
      which are treated by neurotoxin in Asians. METHODS: A panel of experienced Korean
      dermatologists was convened to develop a clinical consensus on common aesthetic
      problems involving the face, neck, and calves in Asians, based on their own
      extensive experience. RESULTS: The consensus recommendations address general
      questions regarding treatment and provide specific guidelines on each common
      aesthetic indication. The recommended final concentration of BTA was 50 U/mL
      after reconstitution with physiologic saline. For horizontal forehead lines, the
      members recommended nine injections in two rows into the frontalis with 1
      U/point. For glabellar lines, the members recommended three injection points (a
      total of 8 U). For crow's feet, the members recommended three injections per side
      (7 U/side) at the lateral part of the orbicularis oculi. For infraorbital
      wrinkles, one to two points per side in the superficial subcutaneous space
      approximately 1 cm below the lash line were recommended (1-2 U/side). For nasal
      flare, one injection point in the middle of each ala nasi was recommended (a
      total of 2 U). For depressed nasal tip, a single injection deep within the
      columella was recommended, with a dose of 3 U. For benign masseter hypertrophy,
      the members recommended a six-point injection to the masseter (three points per
      side for a total of 50-60 U). For the treatment of calf hypertrophy, the members
      recommended a total dose of 100 to 120 U (50-60 U/side), divided between six
      injection points (approximately 8-10 U/point). CONCLUSION: This guideline
      provides a framework for physicians who wish to perform safe and efficacious
      injections of BTA in Asians.

PMID- 24118219
TI  - Modulating effect of d-carvone on 1,2-dimethylhydrazine-induced pre-neoplastic
      lesions, oxidative stress and biotransforming enzymes, in an experimental model
      of rat colon carcinogenesis.
AB  - OBJECTIVES: The present study has aimed to evaluate chemopreventive potential of
      d-carvone on oxidative stress markers, biotransforming enzymes, incidence of
      colonic polyps and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)
      induced experimental colon carcinogenesis. MATERIALS AND METHODS: Rats were
      randomly divided into six groups, with group I serving as control. Group II
      animals received d-carvone every day orally (20 mg/kg body weight) for 16 weeks;
      groups III-VI received subcutaneous injections of DMH (20 mg/kg body weight) once
      a week, for the first 4 weeks. In addition, groups IV-VI received different doses
      of d-carvone (5, 10 and 20 mg/kg body weight everyday orally) along with DMH
      injections. RESULTS: Our results revealed that supplementation with d-carvone
      significantly reduced incidence of polyps/ACF and ACF multiplicity in DMH-exposed
      rats compared to DMH-alone-exposed rats. Moreover, our results showed reduced
      activities of liver and circulatory antioxidants and increased levels of lipid
      peroxidation by products in DMH-exposed animals, which were significantly
      reversed on supplementation with d-carvone. In addition, colonic antioxidants and
      lipid peroxidation were significantly diminished in DMH-exposed rats, which were
      significantly elevated on supplementation with d-carvone. Furthermore, we also
      determined activities of biotransforming enzymes, which were found to be altered
      in DMH-exposed rats, but reversed on d-carvone supplementation. All these
      observations of changes were supported by histochemical findings. CONCLUSION:
      Overall, results obtained from this study suggest that d-carvone at 10 mg/kg body
      weight provided optimum protection and could be used as an effective
      chemopreventive agent against colon carcinogenesis induced by DMH.

PMID- 24118220
TI  - A comparison of pedigree- and DNA-based measures for identifying inbreeding
      depression in the critically endangered Attwater's Prairie-chicken.
AB  - The primary goal of captive breeding programmes for endangered species is to
      prevent extinction, a component of which includes the preservation of genetic
      diversity and avoidance of inbreeding. This is typically accomplished by
      minimizing mean kinship in the population, thereby maintaining equal
      representation of the genetic founders used to initiate the captive population.
      If errors in the pedigree do exist, such an approach becomes less effective for
      minimizing inbreeding depression. In this study, both pedigree- and DNA-based
      methods were used to assess whether inbreeding depression existed in the captive
      population of the critically endangered Attwater's Prairie-chicken (Tympanuchus
      cupido attwateri), a subspecies of prairie grouse that has experienced a
      significant decline in abundance and concurrent reduction in neutral genetic
      diversity. When examining the captive population for signs of inbreeding,
      variation in pedigree-based inbreeding coefficients (f(pedigree)) was less than
      that obtained from DNA-based methods (f(DNA)). Mortality of chicks and adults in
      captivity were also positively correlated with parental relatedness (r(DNA)) and
      f(DNA), respectively, while no correlation was observed with pedigree-based
      measures when controlling for additional variables such as age, breeding
      facility, gender and captive/release status. Further, individual homozygosity by
      loci (HL) and parental rDNA values were positively correlated with adult
      mortality in captivity and the occurrence of a lethal congenital defect in
      chicks, respectively, suggesting that inbreeding may be a contributing factor
      increasing the frequency of this condition among Attwater's Prairie-chickens.
      This study highlights the importance of using DNA-based methods to better inform
      management decisions when pedigrees are incomplete or errors may exist due to
      uncertainty in pairings.

PMID- 24118221
TI  - Determining source strength of semivolatile organic compounds using measured
      concentrations in indoor dust.
AB  - Consumer products and building materials emit a number of semivolatile organic
      compounds (SVOCs) in the indoor environment. Because indoor SVOCs accumulate in
      dust, we explore the use of dust to determine source strength and report here on
      analysis of dust samples collected in 30 US homes for six phthalates, four
      personal care product ingredients, and five flame retardants. We then use a
      fugacity-based indoor mass balance model to estimate the whole-house emission
      rates of SVOCs that would account for the measured dust concentrations. Di-2
      ethylhexyl phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were the most
      abundant compounds in these dust samples. On the other hand, the estimated
      emission rate of diethyl phthalate is the largest among phthalates, although its
      dust concentration is over two orders of magnitude smaller than DEHP and DiNP.
      The magnitude of the estimated emission rate that corresponds to the measured
      dust concentration is found to be inversely correlated with the vapor pressure of
      the compound, indicating that dust concentrations alone cannot be used to
      determine which compounds have the greatest emission rates. The combined dust
      assay modeling approach shows promise for estimating indoor emission rates for
      SVOCs. PRACTICAL IMPLICATIONS: The combined dust-assay modeling approach in this
      study can be used to predict the source strength of indoor released compounds,
      integrating emissions from consumer products, building materials, and other home
      furnishings. Our findings show that estimated emission rates are closely related
      to not only the level of compounds on dust, but also the vapor pressure of the
      compound. Thus, a fugacity-based indoor mass balance model and measured dust
      concentrations can be used to estimate the whole-house emission rates from all
      sources in actual indoor settings, when individual sources of emissions are
      unknown.

PMID- 24118222
TI  - Osteonecrosis of the jaw from bone anti-resorptives: impact of skeletal site
      dependent mesenchymal stem cells.

PMID- 24118223
TI  - Octreotide therapy for the management of refractory chylous ascites after a
      staging operation for endometrial adenocarcinoma.
AB  - Chylous ascites after para-aortic lymphadenectomy is caused by a rupture in the
      retroperitoneal lymphatic channels. The incidence of postoperative chylous
      ascites is increasing as para-aortic lymphadenectomy for the management of
      gynecologic malignancies becomes more common. However, management of this
      condition remains unsatisfactory because some patients do not respond to
      conservative methods and have to undergo surgical intervention, even though they
      may be malnourished and immunosuppressed. We report the case of a patient who
      underwent a standard staging operation for endometrial cancer and experienced a
      large amount of lymphatic leakage, in spite of treatment with total parenteral
      nutrition and a low-fat diet for over 40 days. As a step-up approach, octreotide,
      a somatostatin analog, was added and the disease resolved completely. This case
      demonstrated that octreotide therapy is highly effective in refractory cases of
      chylous ascites where a large amount of leakage is observed and cases that are
      otherwise indicated for surgical intervention. 

PMID- 24118225
TI  - Phrenic nerve damage from cryoablation: dealbreaker or just a hiccup?

PMID- 24118224
TI  - Genetic architecture of sensory exploitation: QTL mapping of female and male
      receiver traits in an acoustic moth.
AB  - The evolution of extravagant sexual traits by sensory exploitation occurs if
      males incidentally evolve features that stimulate females owing to a pre-existing
      environmental response that arose in the context of natural selection. The
      sensory exploitation process is thus expected to leave a specific genetic
      imprint, a pleiotropic control of the original environmental response and the
      novel sexual response in females. However, females may be subsequently selected
      to improve their discrimination of environmental and sexual stimuli. Accordingly,
      responses may have diverged and the original genetic architecture may have been
      modified. These possibilities may be considered by studying the genetic
      architecture of responses to male signals and to the environmental stimuli that
      were purportedly 'exploited' by those signals. However, no previous study has
      addressed the genetic control of sensory exploitation. We investigated this
      question in an acoustic pyralid moth, Achroia grisella, in which a male
      ultrasonic song attracts females and perception of ultrasound likely arose in the
      context of detecting predatory bats. We examined the genetic architecture of
      female response to bat echolocation signals and to male song via a cartographic
      study of quantitative trait loci (QTL) influencing these receiver traits. We
      found several QTL for both traits, but none of them were colocalized on the same
      chromosomes. These results indicate that - to the extent to which male A.
      grisella song originated by the process of sensory exploitation - some
      modification of the female responses occurred since the origin of the male
      signal. 

PMID- 24118226
TI  - Combined paclitaxel-eluting balloon and Genous cobalt-chromium alloy stent
      utilization in de novo coronary stenoses (PEGASUS).
AB  - OBJECTIVES: The aim of this study was to examine the angiographic result and its
      outcome predictors using the combination of paclitaxel-eluting balloon (PEB) and
      Genous stent. BACKGROUND: This approach to treat coronary stenoses is a logical
      strategy to strike a balance between minimizing restenosis and stent thrombosis.
      METHODS: From November 2010 to June 2012, 40 symptomatic patients with 44 de novo
      coronary lesions of diameter stenosis >= 50% were treated with the combination of
      PEB and Genous stents. Angiographic and clinical follow-up were intended at 6 and
      9 months, respectively. RESULTS: The mean age of patients was 61 +/- 11 years,
      with male predominance (83%). Diabetes mellitus and end-stage renal failure on
      peritoneal dialysis were found in 15 (38%) and 10 (25%) patients, respectively.
      Patients received dual antiplatelet therapy for 5.1 +/- 1.5 months post
      procedure. The size and length of PEB used was larger than the stents (3.13 +/-
      0.46 mm and 28 +/- 9 mm vs. 2.98 +/- 0.36 mm and 23 +/- 7 mm). Restudy
      angiography was performed on 41 (95%) lesions in 37 (93%) patients at 5.9 +/- 1.7
      months. Angiographic restenosis was seen in 5 (12%) lesions, and significantly
      associated with diabetes mellitus and dialysis dependency; the late lumen loss
      was 0.38 +/- 0.37 mm. At 9-month follow-up, no stent thrombosis was observed.
      CONCLUSIONS: The use of PEB combined with Genous stent is associated with a
      reasonably low restenosis and late lumen loss, whereas diabetes mellitus and
      renal failure with dialysis are poor predictors of angiographic restenosis.

PMID- 24118227
TI  - Can stable isotope analysis reveal dietary differences among groups with distinct
      income levels in the city of Piracicaba (southeast region, Brazil)?
AB  - BACKGROUND: The present study aimed to determine whether the delta(13)C and
      delta(15)N of fingernails (delta(13)CF and delta(15)NF, respectively) would
      exhibit differences between groups from different income levels in the city of
      Piracicaba, Brazil. METHODS: In 2010, the fingernails of 273 participants
      belonging to six income groups were analysed to determine isotopic composition.
      delta(13)CF and delta(15)NF were compared with the stable isotope of a putative
      diet (delta(13)CD and delta(15)ND , respectively), which was estimated via an
      isotopic mass balance using, as a weighting factor, macronutrient intake by the
      main food items, as obtained by the 2008-2009 household food purchases conducted
      by the Brazilian Institute of Geography and Statistics. RESULTS: delta(13)CF
      values showed a decreasing trend towards the lower income level groups, in
      accordance with the delta(13)CD values that showed the same trend. This isotopic
      change was mainly a result of the higher consumption of beef, bread, soft drinks
      and dairy by the highest income group; and also as a result of the higher
      consumption of soybean oil, rice and sugar by the lowest income group. The
      delta(15)NF values failed to capture differences in groups between income levels.
      This outcome was not expected because individuals in a higher income group tend
      to consume more animal protein and, as a result of the trophic fractionation,
      have higher delta(15)N values. CONCLUSIONS: The combination of household purchase
      surveys and stable isotopic composition in modern humans is found to be a
      valuable tool, especially with respect to determining the role of C3 and C4
      plants through the complex modern food chain.

PMID- 24118228
TI  - Association between statin use and intracerebral hemorrhage: a systematic review
      and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Accumulating evidence suggests that statins exert
      neuroprotective effects, but whether their use affects the outcomes of
      intracerebral hemorrhage (ICH) remains controversial. Therefore, we performed a
      systematic review and meta-analysis to investigate whether statin use before
      spontaneous ICH affects unfavorable functional outcome or mortality. METHODS: We
      searched the Cochrane Library, MEDLINE, EMBASE and China National Knowledge
      Infrastructure databases for studies examining the effects of pre-ICH statin use
      on unfavorable functional outcome, mortality or neuroimaging outcomes in
      consecutively recruited patients with spontaneous ICH, regardless of the duration
      or dose of statin treatment. RESULTS: A total of 12 studies were included that
      examined the effects of pre-ICH statin use on post-ICH outcomes in 1652 subjects
      in the favors pre-statin group and 5309 in the favors no pre-ICH statin group.
      Meta-analysis of 11 studies suggested that pre-ICH statin use did not
      significantly affect mortality across all three time points tested [in-hospital,
      30 days, 90 days; odds ratio (OR) 0.85, 95% confidence interval (CI) 0.70-1.03].
      However, meta-analysis of seven studies showed that pre-ICH statin use did
      significantly decrease 90-day mortality (OR 0.72, 95% CI 0.59-0.88). Meta
      analysis of six studies showed that pre-ICH statin use was not associated with
      significant changes in unfavorable functional outcome. Moreover, pre-ICH statin
      use did not significantly affect admission hematoma volume (standardized mean
      difference 7.75, 95% CI -5.59 to 21.09). CONCLUSION: Available evidence suggests
      that statin use before spontaneous ICH does not increase short-term mortality,
      unfavorable functional outcome or post-ICH hematoma volume at admission.

PMID- 24118229
TI  - Not so temporary pacing.

PMID- 24118230
TI  - c-FOS expression after hippocampal deep brain stimulation in normal rats.
AB  - OBJECTIVES: We studied the effects of Hip-deep brain stimulation (DBS) on the
      expression of the inducible transcription factor c-FOS in the brain of normal
      rats. MATERIALS AND METHODS: Ten Wistar rats were anesthetized, and nine were
      implanted with epidural and hippocampal electrodes for brain activity recording;
      one animal was used as sham. Bipolar stimulating electrodes were implanted in the
      left hippocampus. Three animals were used as control (implanted but not
      stimulated), one as sham (not implanted, not stimulated), and six as the study
      group. Stimulation was carried out using square wave pulses with 0.8V, 300 MUsec,
      and 130 Hz (~25MUC/cm2) on the left hippocampus through the implanted bipolar
      hippocampal lead. Three animals were submitted to a one-hour and three to a six
      hour stimulation session. Immunohistochemistry was employed to visualize c-FOS
      distribution in the rat's brain. The presence of seizures and
      electrocorticographic findings also were observed. RESULTS: In animals submitted
      to both one-hour or six-hour unilateral hippocampal stimulation sessions, there
      was a significant bilateral overexpression of c-FOS in the hippocampus proper,
      dentate gyrus, and hylus. In the CA1 and CA3 regions, although activation was
      bilateral, c-FOS hyperexpression prevailed at the stimulated side over time; this
      was not true for the hilar and dentate gyrus regions where a more symmetric
      activation occurred over time. A significant c-FOS activation occurred after one
      hour of Hip-DBS in the ipsilateral amygdala; there was no contralateral amygdala
      activation, and by six hours, no amygdala activation was noted. No c-FOS
      activation was noted in other brain areas. DISCUSSION: Our data showed that
      unilateral Hip-DBS was able to cause widespread and persistent bilateral
      activation of the normal rat limbic system, although in some, nuclei activation
      prevailed over the stimulated side. Cortical activation outside the limbic system
      was not noted. Our data represent a first approach to study the mechanistic
      paradigm involved in Hip-DBS.

PMID- 24118231
TI  - The human neurosecretory neurones under perinatal hypoxia: a quantitative
      immunohistochemical study of the supraoptic nucleus in autopsy material.
AB  - In the rat, experimental manipulations that cause activation of the magnocellular
      neurosecretory neurones result in the synthesis, in addition to vasopressin (AVP)
      and oxytocin (OXY), of other neurotransmitters or peptides, including tyrosine
      hydroxylase (TH), the first and rate limiting enzyme for catecholamine
      biosynthesis. In the human neonate, our previous study showed that TH was
      selectively increased in AVP neurones of subjects that died from prolonged
      perinatal hypoxia. The purpose of the present study was to quantitatively
      investigate the expression of TH, AVP, OXY and neurophysin in magnocellular
      neurones of the human neonate in relation to the severity/duration of perinatal
      hypoxia, as estimated by neuropathological criteria. Autopsy was performed after
      obtaining parental written consent for diagnostic and research purposes. The
      intensity of the immunohistochemical reactions and the cellular/nuclear size were
      measured in the dorsolateral supraoptic nucleus using a computerised image
      analysis system. We showed that prolonged perinatal hypoxia resulted in the
      activation of the magnocellular neuroendocrine neurones of the human neonate, as
      indicated by their increased neuronal and nuclear size. OXY neurones appeared
      larger than the AVP ones at birth, possibly indicating an active role of foetal
      OXY during labour or even earlier. The gradual increase in the duration of the
      insult resulted in the reduction of intracellular AVP content, in parallel with a
      dramatic increase in the expression of TH, indicating a functional interaction of
      these peptides under neuronal activation. Iotasolated evidence in our series,
      obtained from an infant of a diabetic mother, raises the probability that in the
      case of hyperglycaemia the above pathogenetic mechanisms are diversified. 

PMID- 24118232
TI  - Canonical Wnt signalling as a key regulator of fibrogenesis - implications for
      targeted therapies?
AB  - Canonical Wnt signalling belongs to the so-called morphogen pathways and plays
      essential roles in development and tissue homeostasis. Being such a crucial
      regulatory pathway, Wnt signalling is tightly controlled at different levels.
      However, uncontrolled activation of canonical Wnt signalling has been implicated
      into the pathogenesis of various human disorders. In the last years, aberrant Wnt
      signalling has been demonstrated in fibrotic diseases including systemic
      sclerosis (SSc). In this review, we will discuss the current state of research on
      canonical Wnt signalling in SSc. Activation of canonical Wnt signalling induces
      fibroblast activation with subsequent myofibroblast differentiation and excessive
      collagen release resulting in tissue fibrosis. Genetic or pharmacological
      blockade of Wnt activation ameliorates experimental fibrosis in different
      preclinical models. These findings have direct translational implications because
      several small molecule inhibitors of Wnt signalling are currently evaluated in
      clinical trials and some already showed first promising results. 

PMID- 24118233
TI  - Health-related quality of life after carbon-ion radiotherapy for prostate cancer:
      a 3-year prospective study.
AB  - OBJECTIVES: To assess 3-year health-related quality of life of patients treated
      with carbon ion radiotherapy for prostate cancer. METHODS: A total of 213
      patients received carbon-ion radiotherapy at a total dose of 66 Gy equivalent in
      20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation
      therapy were administered for high-risk patients for at least 12 months. A health
      related quality of life assessment was carried out at four time-points
      (immediately before the initiation of carbon-ion radiotherapy, immediately after,
      12 and 36 months after completion of carbon-ion radiotherapy) using Functional
      Assessment of Cancer Therapy General and for Prostate Cancer Patients. RESULTS:
      The evaluable response rates among all responses were more than 94%. Overall, a
      significant decrease in the scores of the health-related quality of life 12
      months after carbon-ion radiotherapy returned to their baseline levels at 36
      months. Additionally, no significant decrease was observed in the scores at any
      of the assessment time-points compared with their baseline scores in the group of
      carbon-ion radiotherapy without androgen deprivation therapy; however, the
      presence of morbidity and biochemical failure significantly worsened the scores,
      and the decreases in the scores did not improve even at 36 months after carbon
      ion radiotherapy. CONCLUSIONS: An assessment based on a subjective scoring system
      shows a significant decrease in health-related quality of life at 12 months after
      carbon-ion radiation therapy, which tends to return to baseline levels at 36
      months. The presence of morbidity and biochemical failure significantly worsen
      health-related quality of life scores. Further controlled studies focusing on
      health-related quality of life assessment in patients with prostate cancer are
      warranted.

PMID- 24118235
TI  - Signatures of selection in the Iberian honey bee (Apis mellifera iberiensis)
      revealed by a genome scan analysis of single nucleotide polymorphisms.
AB  - Understanding the genetic mechanisms of adaptive population divergence is one of
      the most fundamental endeavours in evolutionary biology and is becoming
      increasingly important as it will allow predictions about how organisms will
      respond to global environmental crisis. This is particularly important for the
      honey bee, a species of unquestionable ecological and economical importance that
      has been exposed to increasing human-mediated selection pressures. Here, we
      conducted a single nucleotide polymorphism (SNP)-based genome scan in honey bees
      collected across an environmental gradient in Iberia and used four FST -based
      outlier tests to identify genomic regions exhibiting signatures of selection.
      Additionally, we analysed associations between genetic and environmental data for
      the identification of factors that might be correlated or act as selective
      pressures. With these approaches, 4.4% (17 of 383) of outlier loci were cross
      validated by four FST -based methods, and 8.9% (34 of 383) were cross-validated
      by at least three methods. Of the 34 outliers, 15 were found to be strongly
      associated with one or more environmental variables. Further support for
      selection, provided by functional genomic information, was particularly
      compelling for SNP outliers mapped to different genes putatively involved in the
      same function such as vision, xenobiotic detoxification and innate immune
      response. This study enabled a more rigorous consideration of selection as the
      underlying cause of diversity patterns in Iberian honey bees, representing an
      important first step towards the identification of polymorphisms implicated in
      local adaptation and possibly in response to recent human-mediated environmental
      changes. 

PMID- 24118234
TI  - Deep phenotyping of the unselected COPSAC2010 birth cohort study.
AB  - BACKGROUND: We hypothesize that perinatal exposures, in particular the human
      microbiome and maternal nutrition during pregnancy, interact with the genetic
      predisposition to cause an abnormal immune modulation in early life towards a
      trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE:
      The aim of this study is to explore these interactions by conducting a
      longitudinal study in an unselected cohort of pregnant women and their offspring
      with emphasis on deep clinical phenotyping, exposure assessment, and biobanking.
      Exposure assessments focus on the human microbiome. Nutritional intervention
      during pregnancy in randomized controlled trials are included in the study to
      prevent disease and to be able to establish causal relationships. METHODS:
      Pregnant women from eastern Denmark were invited during 2008-2010 to a novel
      unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy
      weeks 24 and 36. Their children were followed at the clinic with deep phenotyping
      and collection of biological samples at nine regular visits until the age of 3
      and at acute symptoms. Randomized controlled trials of high-dose vitamin D and
      fish oil supplements were conducted during pregnancy, and a trial of azithromycin
      for acute lung symptoms was conducted in the children with recurrent wheeze.
      RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of
      gestation, and 700 of their children were included in the birth cohort. The
      cohort has an over-representation of atopic parents. The participant satisfaction
      was high and the adherence equally high with 685 children (98%) attending the 1
      year clinic visit and 667 children (95%) attending the 2 year clinic visit.
      CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical
      follow-up with highly specific end-points, exposure assessments, and biobanking.
      The cohort has a high adherence rate promising strong data to elucidate the
      interaction between genomics and the exposome in perinatal life leading to
      lifestyle-related chronic inflammatory disorders such as asthma.

PMID- 24118237
TI  - Nutritional status of haemodialysis patients: comparison of Australian cohorts of
      Aboriginal and European descent.
AB  - AIM: It is not known whether nutritional status differs between Australian
      Aboriginal and non Aboriginal haemodialysis subjects. The aim of this study was
      to investigate the nutritional status of Australian Aboriginal and non-Aboriginal
      haemodialysis subjects at satellite dialysis centres. METHOD: Seventy-six (25
      Aboriginal, 51 non-Aboriginal) prevalent haemodialysis patients were enrolled in
      a 3-month cross-sectional study. Each month anthropometric and biochemical
      measurements were collected. Nutritional status (diet history, patient-generated
      subjective global assessment (PG-SGA), handgrip strength) was assessed by a
      dietitian. RESULTS: PG-SGA detected mild to moderate malnutrition in 35% of
      Aboriginal patients and 25% of non-Aboriginal patients. The overall physical
      rating on the PG-SGA was significantly higher in Aboriginal patients, indicating
      the presence of a greater deficit in muscle mass in this population. Inter
      dialytic weight gain was significantly greater in Aboriginal subjects (median
      [range] 3.0 [2.1-5.7] vs 2.5 [-0.3-5.0] kg, P<0.001). Glucose and HbA1c were
      significantly higher in Aboriginal subjects with diabetes than in non-Aboriginal
      patients with diabetes (median [range] 9.4 [4.9-23.4] vs 5.7 [3.1-12.9], P=0.002;
      7.0 [5.2-11.0] vs 5.8 [4.6-9.0], P<0.000; respectively). These findings occurred
      in the setting of each cohort having adequate dialysis parameters (median Kt/V of
      >1.6 and median normalized protein catabolic rate 1.5). Difficulties were
      encountered in obtaining dietary information from Aboriginal subjects using the
      diet history method. CONCLUSION: Subjects had acceptable parameters of dialysis
      adequacy; however, 35% had evidence of malnutrition. Further research should
      focus on establishing a knowledge base for the nutritional management for
      Aboriginal dialysis subjects, and the development of a validated individual
      dietary assessment method for use in this population group.

PMID- 24118236
TI  - Do people cope with situations as they say? Relationship between perceived coping
      style and actual coping response.
AB  - AIM: The coping style that individuals think they will use when encountering
      stressful situations may differ from actual coping response in real situations.
      METHODS: In a longitudinal study on some 500 university students, perceived
      coping style was identified using the Coping Inventory for Stressful Situations
      on the first occasion. In the subsequent eight test occasions, which occurred on
      a weekly basis, the students were asked about a negative life event that occurred
      during the past week and the actual coping responses they used. RESULTS: The
      perceived coping style and the actual coping response matched well for task
      oriented and emotion-oriented coping. For avoidance-oriented coping, however,
      perceived coping style and actual coping response were weakly correlated.
      CONCLUSION: Epidemiological studies on coping and mental health should
      discriminate coping style and coping response. Clinicians should be cautious
      about patients' own information about avoidance-oriented coping.

PMID- 24118238
TI  - Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic
      acid in horses.
AB  - BACKGROUND: Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and
      tranexamic acid (TEA) are used to treat various bleeding disorders in horses.
      Although horses are hypofibrinolytic compared to humans, dosing schemes have been
      derived from pharmacokinetic studies targeting plasma concentrations in humans.
      HYPOTHESIS/OBJECTIVES: We hypothesized therapeutic plasma concentrations of
      antifibrinolytic drugs in horses would be significantly lower than in humans. Our
      objective was to use thromboleastography (TEG) and an in vitro model of
      hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses
      and humans. ANIMALS: Citrated plasma collected from 24 random source clinically
      healthy research horses. Commercial pooled human citrated plasma with normal
      coagulation parameters was purchased. METHODS: Minimum tissue plasminogen
      activator (tPA) concentration to induce complete fibrinolysis within 10 minutes
      was determined using serial dilutions of tPA in equine plasma. Results used to
      create an in vitro hyperfibrinolysis model with equine and human citrated plasma,
      and the minimum concentrations of EACA and TEA required to completely inhibit
      fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined
      using serial dilutions of the drugs. RESULTS: Estimated therapeutic
      concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI
      3.77-7.86 MUg/mL and 0.512; 95% CI 0.277-0.748 MUg/mL) than in humans (113.2; 95%
      CI 95.8-130.6 MUg/mL and 11.4; 95% CI 8.62-14.1 MUg/mL). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Current dosing schemes for EACA and TEA in horses may be as much as
      20* higher than necessary, potentially increasing cost of treatment and risk of
      adverse effects.

PMID- 24118239
TI  - Arrangement and number of clustered regularly interspaced short palindromic
      repeat spacers are associated with erythromycin susceptibility in emm12, emm75
      and emm92 of group A streptococcus.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) are composed
      of numerous repeat-spacer units and are considered a prokaryotic defence system
      against foreign nucleic acids. Since antibiotic-resistant genes are frequently
      encoded in foreign nucleic acids, the aim of this study was to test whether
      erythromycin susceptibility in group A streptococcus (Streptococcus pyogenes) is
      associated with characteristics of CRISPR elements. Erythromycin susceptibility
      of 330 isolates collected between 1997 and 2003 was analysed. Among 29 emm types,
      emm12, emm75 and emm92 showed significant changes in erythromycin-resistance
      rates. By sequencing the spacers from two CRISPR loci, spacer contents in emm12,
      emm75 and emm92 strains were associated with erythromycin susceptibility. Strains
      with fewer spacers were more resistant to erythromycin. Moreover, in emm4
      strains, which showed no significant change in their annual erythromycin
      resistance rate, CRISPR type and number of spacers were not correlated with
      erythromycin susceptibility. These results highlight a novel association between
      CRISPR spacer content and erythromycin susceptibility in group A streptococcus. 

PMID- 24118240
TI  - Metabolomics reveals that carnitine palmitoyltransferase-1 is a novel target for
      oxidative inactivation in human cells.
AB  - Oxidative dysfunction in the metabolism has long been implicated in diverse
      biological disorders. Although a substantial number of metabolic enzymes are
      targeted for inactivation by oxidative stress, identifying those targets remains
      difficult due to a lack of comprehensive observations of the metabolism acting
      through the stress response. We herein developed a metabolomics strategy using
      integrative liquid chromatography-mass spectrometry (LC-MS) and observing rapid
      metabolomic changes in response to hydrogen peroxide (H2 O2 )-induced oxidative
      stress in HeLa cells. Among the many metabolite changes detected, the most
      characteristic metabolites uniquely indicated carnitine palmitoyltransferase-1
      (CPT1), the critical enzyme for mitochondrial beta-oxidation of long-chain fatty
      acids, to be a target for oxidative inactivation. We showed that the enzymatic
      activity of CPT1 significantly declined by H2 O2 in several human cells.
      Interestingly, the inactivation was shown to be a direct effect of H2 O2 in
      vitro, but substantially occurred when cells were cultured with some reagents
      that generate reactive oxygen species (ROS). Thus, our results suggest the
      generality of CPT1 inhibition under various stress conditions associated with ROS
      generation, providing an insight into a mechanism for oxidative dysfunction in
      mitochondrial metabolism. Our metabolome data additionally suggest that certain
      methyltransferase(s) may be targets of oxidative stress as well. 

PMID- 24118241
TI  - A psychometric analysis of the Rotterdam Renal Replacement Knowledge-Test (R3K-T)
      using item response theory.
AB  - Knowledge is a prerequisite for promoting well-informed decision-making.
      Nevertheless, there is no validated and standardized test to assess the level of
      knowledge among renal patients regarding kidney disease and all treatment
      options. Therefore, the objective of this study was to investigate the
      psychometric properties of such a questionnaire for use in research and practice.
      A 30-item list was validated in four groups: (1) 187 patients on dialysis, (2) 82
      patients who were undergoing living donor kidney transplantation the following
      day, (3) the general population of Dutch residents (n = 515) and (4) North
      American residents (n = 550). The psychometric properties of the questionnaire
      were examined using multidimensional item response theory (MIRT). Norm references
      were also calculated. Five items were found to distort ability estimates
      (Differential item functioning; DIF). MIRT analyses were subsequently carried out
      for the remaining 25 items. Almost all items showed good discrimination and
      difficulty parameters based on the fitted model. Two stable dimensions with 21
      items were retrieved for which norm references for the Dutch and North American,
      dialysis and transplantation groups were calculated. This study resulted in a
      thorough questionnaire, the Rotterdam renal replacement knowledge-test, which
      enables reliable testing of patient's knowledge on kidney disease and treatment
      options in clinic and research.

PMID- 24118242
TI  - Contrast-enhanced endoscopic ultrasound.
AB  - Compared to other imaging modalities, endoscopic ultrasound (EUS) has limitations
      in terms of image enhancement. However, with the availability of contrast agents
      in ultrasonography, EUS has evolved. Contrast-enhanced Doppler EUS (CD-EUS)
      enhances Doppler signals from vessels and is useful for characterizing lesions
      detected by EUS. Moreover, contrast-enhanced harmonic EUS (CH-EUS) with second
      generation ultrasound contrast agents and a broad band transducer allows
      microvessels and parenchymal perfusion to be visualized. Vascularity can also be
      quantitatively analyzed during CH-EUS by generating a time-intensity curve. CE
      EUS is useful for characterizing pancreatic lesions and can detect pancreatic
      adenocarcinomas with a sensitivity of 94%and a specificity of 89% as a result of
      the hypo-enhancement of these lesions. Indeed, CH-EUS is superior to multiple
      detector-computed tomography in terms of the differential diagnosis of small
      lesions that are <=2 cm. CH-EUS complements EUS-guided fine-needle aspiration
      (EUS-FNA) as it identifies the EUS-FNA target and lesions with false-negative EUS
      FNA findings. CH-EUS is also used to estimate the malignant potential of
      gastrointestinal stromal tumors and helps to differentiate between malignant and
      benign lymphadenopathy.

PMID- 24118243
TI  - Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update
      and expansion.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) is an option for the treatment of
      cutaneous malignancy. OBJECTIVE: To present an update and expansion on a previous
      review of the use of PDT in the current literature in the treatment of actinic
      keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC),
      squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL),
      malignant melanoma, and its use in chemoprevention. METHODS: Extensive PubMed
      search January 2013. RESULTS AND CONCLUSIONS: We find sufficient evidence to
      recommend the use of PDT in certain patients in the treatment of AK, Bowen's
      disease, sBCC, and nBCC. It is especially useful in those with contraindications
      to surgery, widespread areas of involvement, and large lesions. Not only can it
      be considered superior to other therapies as far as recovery time, tolerance, and
      cosmetic outcomes, but it also should be considered, when indicated, as first
      line treatment in the above conditions. Investigations continue for the use of
      PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL.

PMID- 24118244
TI  - An exotic invader drives the evolution of plant traits that determine mycorrhizal
      fungal diversity in a native competitor.
AB  - The symbiosis between land plants and arbuscular mycorrhizal fungi (AMF) is one
      of the most widespread and ancient mutualisms on the planet. However, relatively
      little is known about the evolution of these symbiotic plant-fungal interactions
      in natural communities. In this study, we investigated the symbiotic AMF
      communities of populations of the native plant species Pilea pumila (Urticaceae)
      with varying histories of coexistence with a nonmycorrhizal invasive species,
      Alliaria petiolata (Brassicaceae), known to affect mycorrhizal communities. We
      found that native populations of P. pumila with a long history of coexistence
      with the invasive species developed more diverse symbiotic AMF communities. This
      effect was strongest when A. petiolata plants were actively growing with the
      natives, and in soils with the longest history of A. petiolata growth. These
      results suggest that despite the ancient and widespread nature of the plant-AMF
      symbiosis, the plant traits responsible for symbiotic preferences can,
      nevertheless, evolve rapidly in response to environmental changes. 

PMID- 24118245
TI  - Anorectal abscess during pregnancy.
AB  - Anorectal symptoms and complaints caused by hemorrhoids or anal fissures are
      common during pregnancy. It is known that one-third of pregnant women complain of
      anal pain in the third trimester. Anal pain may be caused by a wide spectrum of
      conditions, but if it begins gradually and becomes excruciating within a few days
      it may indicate anorectal abscess. We experienced a case of anorectal abscess
      during pregnancy which was diagnosed by magnetic resonance imaging and treated by
      incision and seton drainage at 36 weeks of gestation, followed by a normal
      spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the
      first case report of anorectal abscess during pregnancy in the English-language
      published work. The clinical course of our case and clinical considerations of
      anorectal abscesses are discussed. 

PMID- 24118246
TI  - How Accurate is the AHRQ Patient Safety Indicator for Hospital-Acquired Pressure
      Ulcer in a National Sample of Records?
AB  - In 2008, we conducted a retrospective cross-sectional study to determine the test
      characteristics of the Agency for Healthcare Research and Quality patient safety
      indicator (PSI) for hospital-acquired pressure ulcer (PU). We sampled 1,995
      inpatient records that met PSI 3 criteria and 4,007 records assigned to 14 DRGs
      with the highest empirical rates of PSI 3, which did not meet PSI 3 criteria,
      from 32 U.S. academic hospitals. We estimated the positive predictive value
      (PPV), sensitivity, and specificity of PSI 3 using both the software version
      contemporary to the hospitalizations (v3.1) and an approximation of the current
      version (v4.4). Of records that met PSI 3 version 3.1 criteria, 572 (PPV 28.3%;
      95% CI 23.6-32.9%) were true positive. PU that was present on admission (POA)
      accounted for 76% of the false-positive records. Estimated sensitivity was 48.2%
      (95% CI 41.0-55.3%) and specificity 71.4% (95% CI 68.3-74.5%). Reclassifying
      records based on reported POA information and PU stage to approximate version 4.4
      of PSI 3 improved sensitivity (78.6%; 95% CI 62.7-94.5%) and specificity (98.0;
      95% CI 97.1-98.9%). In conclusion, accounting for POA information and PU staging
      to approximate newer versions of the PSI software (v4.3) moderately improves
      validity. 

PMID- 24118247
TI  - How to distinguish altruism from spite (and why we should bother).
AB  - Social behaviour is often described as altruistic, spiteful, selfish or mutually
      beneficial. These terms are appealing, but it has not always been clear how they
      are defined and what purpose they serve. Here, I show that the distinctions among
      them arise from the ways in which fitness is partitioned: none can be drawn when
      the fitness consequences of an action are wholly aggregated, but they manifest
      clearly when the consequences are partitioned into primary and secondary
      (neighbourhood) effects. I argue that the primary interaction is the principal
      source of adaptive design, because (i) it is this interaction that determines the
      fit of an adaptation and (ii) it is the actor and primary recipients whom an
      adaptation foremost affects. The categories of social action are thus
      instrumental to any account of evolved function. 

PMID- 24118248
TI  - Serum-free media for the production of human mesenchymal stromal cells: a review.
AB  - The regenerative potential of mesenchymal stromal cells (MSC) holds great promise
      in using them for treatment of a wide range of debilitating diseases. Several
      types of culture media and systems have been used for large-scale expansion of
      MSCs in vitro; however, the majority of them rely heavily on using foetal bovine
      serum (FBS)-supplement for optimal cell proliferation. FBS-based cultures pose
      the potential threat of spread of transmissible spongiform encephalopathy and
      bovine spongiform encephalopathy to MSCs and then to their recipients. A recent
      trend in cell culture is to change from serum-use to serum-free media (SFM). In
      this context, the current review focuses specifically on employment of various
      SFM for MSCs and discusses existences of various options with which to substitute
      FBS. In addition, we analyse MSC population growth kinetic patterns using various
      SFM for large-scale production of MSCs. 

PMID- 24118249
TI  - Sex-related and non-sex-related comorbidity subtypes of tic disorders: a latent
      class approach.
AB  - BACKGROUND AND PURPOSE: Recent evidence suggests that there may be more than one
      Gilles de la Tourette syndrome (GTS)/tic disorder phenotype. However, little is
      known about the common patterns of these GTS/tic disorder-related comorbidities.
      In addition, sex-specific phenomenological data of GTS/tic disorder-affected
      adults are rare. Therefore, this community-based study used latent class analyses
      (LCA) to investigate sex-related and non-sex-related subtypes of GTS/tic
      disorders and their most common comorbidities. METHODS: The data were drawn from
      the PsyCoLaus study (n = 3691), a population-based survey conducted in Lausanne,
      Switzerland. LCA were performed on the data of 80 subjects manifesting
      motor/vocal tics during their childhood/adolescence. Comorbid attention-deficit
      hyperactivity disorder (ADHD), obsessive-compulsive disorder, depressive, phobia
      and panic symptoms/syndromes comprised the selected indicators. The resultant
      classes were characterized by psychosocial correlates. RESULTS: In LCA, four
      latent classes provided the best fit to the data. We identified two male-related
      classes. The first class exhibited both ADHD and depression. The second class
      comprised males with only depression. Class three was a female-related class
      depicting obsessive thoughts/compulsive acts, phobias and panic attacks. This
      class manifested high psychosocial impairment. Class four had a balanced sex
      proportion and comorbid symptoms/syndromes such as phobias and panic attacks. The
      complementary occurrence of comorbid obsessive thoughts/compulsive acts and ADHD
      impulsivity was remarkable. CONCLUSIONS: To the best of our knowledge, this is
      the first study applying LCA to community data of GTS symptoms/tic disorder
      affected persons. Our findings support the utility of differentiating GTS/tic
      disorder subphenotypes on the basis of comorbid syndromes.

PMID- 24118250
TI  - Relationship between complex fractionated atrial electrograms during atrial
      fibrillation and the critical site of atrial tachycardia that develops after
      catheter ablation for atrial fibrillation.
AB  - INTRODUCTION: Complex fractionated atrial electrograms (CFAEs) are a substrate
      modification target in patients with atrial fibrillation (AF). However, whether
      CFAEs can be also arrhythmogenic grounds of atrial tachycardia (AT) presenting
      after AF ablation remains to be determined. We investigated the relationship
      between CFAEs and the critical site of AT after CFAE-guided AF ablation. METHODS
      AND RESULTS: Seventy-two patients showing AT after pulmonary vein isolation and
      further CFAE-guided ablation were included. The termination sites of the 95
      distinct ATs were annotated on color-coded CFAE cycle maps. Of the 95 ATs, 61
      (64.2%) had a termination site at the border zone of CFAE or in a highly dense
      CFAE area. The cycle length (CL) of the ATs terminated in the CFAE area was
      significantly shorter than the CL of those terminated in the non-CFAE area. The
      cut-off CL for ATs terminated at the CFAE area was 270 milliseconds, with
      sensitivity/specificity of 70%/75%. In 67.2% of the ATs terminating at the CFAE
      related area, the major termination sites were the anterior wall near the LA
      appendage, septum and roof, whereas the peri-mitral isthmus was the most common
      termination site of ATs in the non-CFAE area. CONCLUSIONS: The areas showing CFAE
      and their border zones were frequently associated with termination of ATs
      presenting after AF ablation. The mean CL of ATs originating near CFAEs was
      significantly shorter than that of those terminated in non-CFAE areas. The
      targeted CFAE areas also provided the arrhythmogenic milieu for AT developing
      after AF ablation.

PMID- 24118251
TI  - Incidence of arteriovenous fistula closure due to high-output cardiac failure in
      kidney-transplanted patients.
AB  - BACKGROUND: Some hemodialysis patients develop arteriovenous (AV) fistulas with
      high flows. This volume overload can result in high-output cardiac failure. To
      date, predisposing access flow rates are unknown. METHODS: A retrospective study
      of all kidney-transplant recipients at the Medical University of Innsbruck (MUI)
      from 2005 to 2010 included 797 patients with the following criteria: previous
      hemodialysis with a native AV fistula or a graft, sufficient function of the
      kidney transplant up to the time of the data analysis, and follow-up care at the
      MUI. RESULTS: Twenty-nine of the 113 patients (25.7%) needed an AV fistula
      closure, mostly because of symptoms of cardiac failure. The mean shunt flow in
      the intervention group was 2197.2 mL/min, whereas the mean shunt flow in the non
      intervention group was only 850.9 mL/min. Shunt closures were most frequently
      made in patients with upper-arm shunts (41.7%). CONCLUSION: The necessity of
      shunt closure is not a rarity. Patients who underwent an AV fistula ligature had
      high access flows with about 2200 mL/min. As the symptoms of cardiac failure
      greatly improved after shunt closure, patients with high access flow may benefit
      from such an intervention.

PMID- 24118252
TI  - Radon in indoor air of primary schools: a systematic survey to evaluate factors
      affecting radon concentration levels and their variability.
AB  - In order to optimize the design of a national survey aimed to evaluate radon
      exposure of children in schools in Serbia, a pilot study was carried out in all
      the 334 primary schools of 13 municipalities of Southern Serbia. Based on data
      from passive measurements, rooms with annual radon concentration >300 Bq/m(3)
      were found in 5% of schools. The mean annual radon concentration weighted with
      the number of pupils is 73 Bq/m(3), 39% lower than the unweighted 119 Bq/m(3)
      average concentration. The actual average concentration when children are in
      classrooms could be substantially lower. Variability between schools (CV = 65%),
      between floors (CV = 24%) and between rooms at the same floor (CV = 21%) was
      analyzed. The impact of school location, floor, and room usage on radon
      concentration was also assessed (with similar results) by univariate and
      multivariate analyses. On average, radon concentration in schools within towns is
      a factor of 0.60 lower than in villages and at higher floors is a factor of 0.68
      lower than ground floor. Results can be useful for other countries with similar
      soil and building characteristics. PRACTICAL IMPLICATIONS: On average, radon
      concentrations are substantially higher in schools in villages than in schools
      located in towns (double,on average). Annual radon concentrations exceeding 300
      Bq/m3 were found in 5% of primary schools (generally on ground floors of schools
      in villages). The considerable variability of radon concentration observed
      between and within floors indicates a need to monitor concentrations in several
      rooms for each floor. A single radon detector for each room can be used provided
      that the measurement error is considerable lower than variability of radon
      concentration between rooms.

PMID- 24118253
TI  - Extreme externalization of riata intracardiac cardioverter defibrillator leads: a
      new peril of a troublesome lead.

PMID- 24118254
TI  - Annexin A1 complex mediates oxytocin vesicle transport.
AB  - Oxytocin is a major neuropeptide that modulates the brain functions involved in
      social behaviour and interaction. Despite of the importance of oxytocin for the
      neural control of social behaviour, little is known about the molecular
      mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin
      is synthesised in the cell bodies of hypothalamic neurones in the supraoptic and
      paraventricular nuclei and processed to a 9-amino-acid mature form during post
      Golgi transport to the secretion sites at the axon terminals and somatodendritic
      regions. Oxytocin secreted from the somatodendritic regions diffuses throughout
      the hypothalamus and its neighbouring brain regions. Some oxytocin-positive axons
      innervate and secrete oxytocin to the brain regions distal to the hypothalamus.
      Brain oxytocin binds to its receptors in the brain regions involved in social
      behaviour. Oxytocin is also secreted from the axon terminal at the posterior
      pituitary gland into the blood circulation. We have discovered a new molecular
      complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150)
      and microtubule motor that controls the distribution of oxytocin vesicles between
      the axon and the cell body in a protein kinase A (PKA)- and protein kinase C
      (PKC)-sensitive manner. ANXA1 showed significant co-localisation with oxytocin
      vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1,
      thus increasing the axon-localisation of oxytocin vesicles. Conversely,
      activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating
      the axon-localisation of oxytocin vesicles. The result of the present study
      suggest that ANXA1 complex coordinates the actions of PKA and PKC to control the
      distribution of oxytocin vesicles between the axon and the cell body.

PMID- 24118255
TI  - Secondary contact and changes in coastal habitat availability influence the
      nonequilibrium population structure of a salmonid (Oncorhynchus keta).
AB  - Numerous empirical studies have reported lack of migration-drift equilibrium in
      wild populations. Determining the causes of nonequilibrium population structure
      is challenging because different evolutionary processes acting at a variety of
      spatiotemporal scales can produce similar patterns. Studies of contemporary
      populations in northern latitudes suggest that nonequilibrium population
      structure is probably caused by recent colonization of the region after the last
      Pleistocene ice age ended ~13,000 years ago. The chum salmon's (Oncorhynchus
      keta) range was fragmented by dramatic environmental changes during the
      Pleistocene. We investigated the population structure of chum salmon on the North
      Alaska Peninsula (NAP) and, using both empirical data and simulations, evaluated
      the effects of colonization timing and founder population heterogeneity on
      patterns of genetic differentiation. We screened 161 single nucleotide
      polymorphisms and found evidence of nonequilibrium population structure when the
      slope of the isolation-by-distance relationship was examined at incremental
      spatial scales. In addition, simulations suggested that this pattern closely
      matched models of recent colonization of the NAP by secondary contact. Our
      results agree with geological and archaeological data indicating that the NAP was
      a dynamic landscape that may have been more recently colonized than during the
      last deglaciation because of dramatic changes in coastal hydrology over the last
      several thousand years.

PMID- 24118256
TI  - Editorial comment to "Is overactive bladder a brain disease? The
      pathophysiological role of cerebral white matter in the elderly".

PMID- 24118257
TI  - Investigation of deep brain stimulation mechanisms during implantable pulse
      generator replacement surgery.
AB  - BACKGROUND: Direct testing of deep brain stimulation (DBS) mechanisms in humans
      is needed to assess therapy and to understand stimulation effects. OBJECTIVE: We
      developed an innovative paradigm for investigation of DBS on human movement
      disorders. Temporary connection to the DBS electrode during implantable pulse
      generator (IPG) replacement permitted analysis of novel patterns of stimulation
      on motor symptoms, which could enhance efficacy and improve battery life.
      MATERIALS AND METHODS: Patients enrolled in this prospective, Institutional
      Review Board-approved study underwent IPG replacement using local (monitored)
      anesthesia. Following device explant, the DBS electrode was connected to an
      external, isolated electrical stimulator using a sterile adapter cable. Different
      temporal patterns of stimulation were delivered while quantifying upper-extremity
      tremor (tri-axial accelerometry) or bradykinesia (finger-tapping). Upon
      experiment completion, the new IPG was implanted. RESULTS: Among 159 IPG
      replacements from 2005 to 2011, 56 patients agreed to the research study (16
      essential tremor [ET], 31 Parkinson's disease [PD], 5 mixed ET/PD tremor, 3
      multiple sclerosis, 1 tremor/myoclonus). Surgical procedures were extended by 42
      +/- 8.2 min in 37 patients completing the study. Motor symptoms varied with
      stimulation pattern, with some patterns showing improved tremor or bradykinesia
      control. No postoperative infections or complications were observed in the 159
      patients. CONCLUSION: IPG replacement occurs when the DBS/brain interface is
      stable and patients demonstrate symptom reduction with known stimulation
      parameters. Conducting research at this time point avoids DBS implant issues,
      including temporary microlesion effects, fluctuating electrode impedances, and
      technical limitations of contemporary IPGs, providing advantageous conditions to
      conduct translational DBS research with minimal additional risk to research
      subjects.

PMID- 24118258
TI  - The mediating role of health professionals' recommendation in the uptake of
      colorectal cancer testing among older Chinese adults.
AB  - The purpose of this study is to examine the mediating effect of health
      professionals' recommendations on the relationship between the characteristics of
      older Chinese adults and the use of colorectal cancer testing. This was a cross
      sectional population-based telephone survey. A total of 2004 Chinese adults aged
      50 or above were recruited between 2 and 28 May 2007 to complete an anonymous
      telephone survey. The survey covered demographics, perceived health status and
      susceptibility to cancer, utilization of complementary medicine, family history
      of cancer, and cancer screening behaviour. The uptake of flexible
      sigmoidoscopy/colonoscopy was 12%, of which only 3.4% had been recommended by
      health professionals. The effects of gender, a history of serious disease,
      perceptions related to health status and visiting doctor regularly on the
      flexible sigmoidoscopy/colonoscopy uptake were mediated by a health
      professional's recommendation. A health professional's recommendation can be a
      catalyst for the decision of undergoing a colorectal cancer screening test in
      older adult people, in particular for those who are more health-conscious. As
      health professionals can play a crucial role in the development of successful
      population-based colorectal cancer screening program, efforts should be made to
      facilitate them in making recommendations for colorectal cancer screening to
      targeted high-risk group. 

PMID- 24118259
TI  - Evaluation of 4 point-of-care units for the determination of blood l-lactate
      concentration in cattle.
AB  - BACKGROUND: Despite being used commonly in bovine medicine, information on
      reliability of point-of-care (POC) lactate meters is limited. OBJECTIVE: To
      determine the validity of 4 commercially available POC lactate meters in cattle.
      ANIMALS: Cattle with various diseases (n = 120). METHODS: Blood samples collected
      from the jugular vein were processed immediately on POC lactate meters. Plasma l
      lactate concentration was measured by the enzymatic-colorimetric method (ELISA).
      Data were subjected to Friedman's test for comparison, Passing-Bablok regression
      and Bland-Altman plot analyses for reliability, and receiver operating
      characteristics analysis for sensitivity (Se) and specificity (Sp). RESULTS: The
      POC lactate meters were highly correlated with ELISA (r = 0.98-0.99) despite
      disagreements among units. When regressed on ELISA, blood l-lactate
      concentrations generated from Accutrend Plus and Lactate Pro were linear up to
      16.6 and 15.7 mmol/L, respectively, whereas those generated from i-STAT and
      Lactate Scout were linear up to 19.5 and 19.7 mmol/L, respectively. All POC
      lactate meters had a Se of 100% with Sp of 95.7-98.6% at a plasma l-lactate cut
      off concentration of 4 mmol/L. i-STAT had the best accuracy (99.0%) and precision
      (99.8%), the best linear fit (y = -0.13 + 1.04X) yielding the lowest bias (-6.6%)
      as well as the highest Se (100%) and Sp (98.6%). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Despite high correlation with the reference method, dilution is
      needed for Accutrend Plus/Lactate Pro and i-STAT/Lactate Scout if concentrations
      >15 and 20 mmol/L, respectively. i-STAT provided the most accurate and precise
      results.

PMID- 24118260
TI  - Adjusting to chronic illness: time for a unified theory.

PMID- 24118261
TI  - Bleomycin inhibits adipogenesis and accelerates fibrosis in the subcutaneous
      adipose layer through TGF-beta1.
AB  - Systemic sclerosis [scleroderma (SSc)]-associated skin fibrosis is characterized
      by increased fibrosis in the dermis and a reduction in the thickness of the
      subcutaneous adipose tissue layer. Although many studies have examined fibrosis
      in SSc, only a few studies have focused on the associated reduction in the
      thickness of the subcutaneous adipose tissue layer. In this study, we
      investigated the effects of SSc-induced fibrosis on adipose tissue. We found that
      bleomycin suppresses adipogenesis in adipose-derived stem cells (ASCs) and
      stimulates ASCs to express transforming growth factor beta1 (TGF-beta1), which
      suppresses adipogenesis and promotes fibrosis. Furthermore, we found that
      adipocyte-conditioned medium suppressed collagen synthesis by fibroblasts in
      fibrosis-like conditions. We concluded that in the skin affected by bleomycin
      induced fibrosis, increased TGF-beta1 expression suppresses adipogenesis and
      promotes adipocyte fibrosis. It was also suggested that adipocytes have an
      inhibitory effect on the progression of fibrosis. 

PMID- 24118262
TI  - One year incidence of iatrogenic atrial septal defect after cryoballoon ablation
      for atrial fibrillation.
AB  - INTRODUCTION: Pulmonary vein (PV) isolation by means of cryoballoon (CB)
      technology is an effective treatment for symptomatic paroxysmal atrial
      fibrillation (AF) refractory to antiarrhythmic drug therapy. The CB requires a
      15F transseptal sheath that may lead to the creation of a iatrogenic atrial
      septal defect (IASD). METHODS AND RESULTS: Individuals having undergone PV
      isolation by the means of CB ablation and a subsequent transesophageal
      echocardiography (TEE) examination during postablation follow-up were
      consecutively included. Thirty-nine patients formed the study group (31 male,
      76.9%; mean age 57.4 +/- 13.7 years). IASD was present in 8 (20%) of them after a
      mean follow-up time of 11.7 months. Mean diameter of the defect was 0.57 cm *
      0.48 cm; only left to right shunt was observed. No adverse events were recorded
      in these patients during the follow-up. CONCLUSION: IASD after CB ablation of AF
      is present in up to 20% of patients after 1 year. Although no adverse clinical
      events were recorded in patients with persistence of IASD, this complication
      should not be underestimated and systematic echocardiographic examinations might
      be advised at regular intervals in the follow-up period after CB. Further studies
      with larger population and follow-up might be required to confirm our findings.

PMID- 24118263
TI  - Cytodiagnosis of endometrial carcinoma and hyperplasia on imprint smears with
      additional immunocytochemistry using Ki-67 and p53 biomarkers.
AB  - OBJECTIVE: It is said to be difficult to interpret the different endometrial
      lesions by cytomorphology; however, evaluation of the microarchitecture of the
      cell clumps and application of immunocytochemistry can improve diagnostic
      accuracy. The aim of the present study was to evaluate cytolomorphological
      features and correlate them with the histological diagnosis of benign and
      malignant endometrial lesions, and to investigate certain immunocytochemical
      biomarkers to achieve a more accurate cytodiagnosis. METHODS: In the present
      study, we graded the cytomorphology on imprint smears of 35 low-grade endometrial
      endometrioid carcinomas compared with 23 cases of endometrium ranging from
      disordered proliferative to benign hyperplastic. Additionally, 10 cases of high
      grade endometrial carcinoma and 11 cases of atrophic endometrium were evaluated.
      Ki-67 and p53 biomarkers were applied to the cytological smears. RESULTS: A total
      cytological score less than six, resulting from nuclear overlapping,
      nuclear/cytoplasmic ratio, the presence of a branched pattern, vesicular
      cytoplasm and loss of cohesiveness, distinguished all the cases of disordered
      proliferative and benign hyperplastic endometrium from low-grade endometrioid
      carcinomas of endometrium (P < 0.0001). The application of different cut-off
      values for Ki-67 and p53 helped differentiate certain endometrial lesions in our
      study. The integration of the immunocytochemical score of Ki-67 and p53 into the
      cytological score resulted in a final score that was also diagnostically useful.
      CONCLUSIONS: The results of the present study demonstrated that evaluation of
      certain cytological features along with specific immunocytochemical findings
      could improve the accuracy of endometrial cytodiagnosis but our findings need to
      be tested in a routine clinical situation, using pre-operative cytological
      samples, to ascertain whether the diagnostic criteria are reproducible.

PMID- 24118265
TI  - Discuss the impact technological advances in equipment and materials have made on
      the delivery and outcome of endodontic treatment.
AB  - Recent advances in endodontic equipment and materials have considerably changed
      the manner in which endodontic treatment is delivered. Specific technological
      advances, including nickel-titanium instruments, ultrasonic instruments and the
      dental operating microscope have been associated with increased efficiency and
      efficacy of treatment and simplification of delivery. The effects of most of
      these changes have been tested via in vitro studies and case reports. Ongoing
      studies should constantly investigate what effects technological advances might
      have on the outcome of endodontic treatment. 

PMID- 24118266
TI  - Clinical and ultrasonographic correlation of acne scars.
AB  - BACKGROUND: Consensus concerning nomenclature and classification of acne scars is
      lacking. Classification based solely on clinical examination represents an unmet
      need that could be improved with the use of objective, reproducible assessments.
      OBJECTIVE: To assess clinical and ultrasound morphologic features in 41 patients
      with scars resulting from moderate to severe acne and to determine whether
      correlation exists. MATERIALS AND METHODS: Eighty-one lesions clinically
      identified as boxcar, ice pick, rolling, hypertrophic, or keloidal were evaluated
      using high-frequency ultrasound (22 MHz). RESULTS: Ultrasound results generally
      correlated with clinical appearance. Eight scars clinically classified as ice
      pick showed a typical boxcar morphology upon ultrasound examination. Ultrasound
      showed that ice pick and boxcar scars were the deepest, with 95.8% between 0.2
      and 0.5 mm. CONCLUSIONS: High-frequency ultrasound is a noninvasive technique
      that is useful in the evaluation and correct classification of acne scars. It
      represents an important adjunct to clinical examination, because it provides
      reliable objective and reproducible information useful to the selection of the
      best treatment option specifically customized to each individual patient's needs.

PMID- 24118267
TI  - Oral candidosis in relation to oral immunity.
AB  - Symptomatic oral infection with Candida albicans is characterized by invasion of
      the oral epithelium by virulent hyphae that cause tissue damage releasing the
      inflammatory mediators that initiate and sustain local inflammation. Candida
      albicans triggers pattern-recognition receptors of keratinocytes, macrophages,
      monocytes and dendritic cells, stimulating the production of IL-1beta, IL-6 and
      IL-23. These cytokines induce the differentiation of Th17 cells and the
      generation of IL-17- and/or IL-22-mediated antifungal protective immuno
      inflammatory responses in infected mucosa. Some immune cells including NKT cells,
      gammadelta T cells and lymphoid cells that are innate to the oral mucosa have the
      capacity to produce large quantities of IL-17 in response to C. albicans,
      sufficient to mediate effective protective immunity against C. albicans. On the
      other hand, molecular structures of commensal C. albicans blastoconidia, although
      detected by pattern-recognition receptors, are avirulent, do not invade the oral
      epithelium, do not elicit inflammatory responses in a healthy host, but induce
      regulatory immune responses that maintain tissue tolerance to the commensal
      fungi. The type, specificity and sensitivity of the protective immune response
      towards C. albicans is determined by the outcome of the integrated interactions
      between the intracellular signalling pathways of specific combinations of
      activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL
      17-mediated protective immune response is essential for oral mucosal immunity to
      C. albicans infection.

PMID- 24118268
TI  - Successful cavotricuspid isthmus ablation in a patient with a senning operation
      and prosthetic tricuspid valve replacement.

PMID- 24118270
TI  - Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced
      apical root resorption.
AB  - OBJECTIVE: Orthodontic-induced external apical root resorption (EARR) is a
      complex phenotype determined by poorly defined mechanical and patient intrinsic
      factors. The aim of this work was to construct a multifactorial integrative
      model, including clinical and genetic susceptibility factors, to analyze the risk
      of developing this common orthodontic complication. MATERIALS AND METHODS: This
      retrospective study included 195 orthodontic patients. Using a multiple-linear
      regression model, where the dependent variable was the maximum% of root
      resorption (%EARRmax) for each patient, we assessed the contribution of nine
      clinical variables and four polymorphisms of genes involved in bone and tooth
      root remodeling (rs1718119 from P2RX7, rs1143634 from IL1B, rs3102735 from
      TNFRSF11B, encoding OPG, and rs1805034 from TNFRSF11A, encoding RANK). RESULTS:
      Clinical and genetic variables explained 30% of%EARRmax variability. The
      variables with the most significant unique contribution to the model were: gender
      (P < 0.05), treatment duration (P < 0.001), premolar extractions (P < 0.01),
      Hyrax appliance (P < 0.001) and GG genotype of rs1718119 from P2RX7 gene (P <
      0.01). Age, overjet, tongue thrust, skeletal class II and the other polymorphisms
      made minor contributions. CONCLUSION: This study highlights the P2RX7 gene as a
      possible factor of susceptibility to EARR. A more extensive genetic profile may
      improve this model.

PMID- 24118269
TI  - Methylphenidate for attention deficit hyperactivity disorder and drug relapse in
      criminal offenders with substance dependence: a 24-week randomized placebo
      controlled trial.
AB  - AIM: To test the efficacy and safety of osmotic release oral system (OROS)
      methylphenidate (MPH) in doses up to 180 mg/day to treat attention deficit
      hyperactivity disorder (ADHD) and prevent any drug relapse in individuals with a
      co-diagnosis of ADHD and amphetamine dependence. DESIGN: Randomized placebo
      controlled 24-week double-blind trial with parallel groups design. SETTING:
      Participants were recruited from medium security prisons in Sweden. The
      medication started within 2 weeks before release from prison and continued in out
      patient care with twice-weekly visits, including once-weekly cognitive
      behavioural therapy. PARTICIPANTS: Fifty-four men with a mean age of 42 years,
      currently incarcerated, meeting DSM-IV criteria for ADHD and amphetamine
      dependence. MEASUREMENTS: Change in self-reported ADHD symptoms, relapse to any
      drug use (amphetamine and other drugs) measured by urine toxicology, retention to
      treatment, craving and time to relapse. FINDINGS: The MPH-treated group reduced
      their ADHD symptoms during the trial (P = 0.011) and had a significantly higher
      proportion of drug-negative urines compared with the placebo group (P = 0.047),
      including more amphetamine-negative urines (P = 0.019) and better retention to
      treatment (P=0.032). CONCLUSIONS: Methylphenidate treatment reduces attention
      deficit hyperactivity disorder symptoms and the risk for relapse to substance use
      in criminal offenders with attention deficit hyperactivity disorder and substance
      dependence.

PMID- 24118264
TI  - Explicit tests of palaeodrainage connections of southeastern North America and
      the historical biogeography of Orangethroat Darters (Percidae: Etheostoma:
      Ceasia).
AB  - The alteration in palaeodrainage river connections has shaped patterns of
      speciation, genetic diversity and the geographical distribution of the species
      rich freshwater fauna of North America. The integration of ancestral range
      reconstruction methods and divergence time estimates provides an opportunity to
      infer palaeodrainage connectivity and test alternative palaeodrainage hypotheses.
      Members of the Orangethroat Darter clade, Ceasia, are endemic to southeastern
      North America and occur north and south of the Pleistocene glacial front, a
      distributional pattern that makes this clade of closely related species an ideal
      system to investigate the number and location of glacial refugia and compare
      alternative hypotheses regarding the proposed evolution of the Teays-Mahomet
      palaeodrainage. This study utilized time-calibrated mitochondrial and nuclear
      gene phylogenies and present-day geographical distributions to investigate
      hypothesized Teays-Mahomet River connections through time using a dispersal
      extinction-cladogenesis (DEC) framework. Results of DEC ancestral area
      reconstructions indicate that the Teays-Mahomet River was a key dispersal route
      between disjunct highland regions connecting the Mississippi River tributaries to
      the Old-Ohio Drainage minimally at two separate occasions during the Pleistocene.
      There was a dynamic interplay between palaeodrainage connections through time and
      postglacial range expansion from three glacial refugia that shaped the current
      genetic structure and geographical distributions of the species that comprise
      Ceasia. 

PMID- 24118271
TI  - ABO incompatible living donor kidney transplantation in Korea: highly uniform
      protocols and good medium-term outcome.
AB  - The organ shortage is as serious in Korea as in other parts of the world. As
      about one-third of the potential living donors are ABO incompatible (ABOi),
      transplantation across the blood group barrier can help overcome this shortage.
      One hundred and twenty-five ABOi kidney transplantations (KTs) were performed
      between 2007 and 2010 in Korea. We collected the perioperative and follow-up data
      for 118 of these patients until September 2011. The preconditioning and
      immunosuppressive protocols were almost identical across the different transplant
      centers, with rituximab but no splenectomy; pre-transplant plasmapheresis (PP)
      with target anti-A/B titer 8 or 16 on transplant day, on-demand, rather than
      routine, post-transplant PP, and tacrolimus-based immunosuppressants. The number
      of patients and participating centers showed a rapid increase over time, and in
      2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The
      mean follow-up period was 21 months (range, 1-56 months). Sixteen (14%) patients
      developed acute rejection, and three of these had antibody-mediated rejection
      (AMR). Two-yr patient and graft survival were 99.2% and 97.5%, respectively. No
      graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent
      medium-term outcome and will help mitigate the organ shortage.

PMID- 24118272
TI  - Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and
      recurrence after liver transplantation for hepatocellular cancer.
AB  - There is increasing evidence that systemic inflammation markers like neutrophil
      (NLR) and platelet-to-lymphocyte ratios (PLR) may play a role in the outcome of
      hepatocellular cancer (HCC). Between January 1994 and March 2012, 181 patients
      with HCC were registered on the transplant waiting list: 35 (19.3%) patients
      dropped out during the waiting period and 146 (80.7%) patients underwent liver
      transplantation (LT). The median follow-up of this patient cohort was 4.2 years
      (IQR: 1.8-8.3). On c-statistics, the last NLR (AUROC = 67.4; P = 0.05) was the
      best predictor of dropout. The last PLR had an intermediate statistical ability
      (AUROC = 66.1; P = 0.07) to predict post-LT tumor recurrence. Patients with a NLR
      value >5.4 had poor 5-year intention-to-treat (ITT) survival rates (48.2 vs.
      64.5%; P = 0.02). Conversely, PLR better stratified patients in relation to tumor
      free survival (TFS) (80.7 vs. 91.6%; P = 0.02). NLR is a good predictor for the
      risk of dropout, while PLR is a good predictor for the risk of post-LT
      recurrence. Use of these markers, which are all available before LT, may
      represent an additional tool to refine the selection criteria of HCC liver
      recipients.

PMID- 24118273
TI  - Evidence-based practice for pain management for cancer patients in an acute care
      setting.
AB  - The purpose of this study is to implement an evidence utilization project using
      an audit and feedback approach to improve cancer pain management. A three-phased
      audit and feedback approach was used. A 46-bed oncology nursing unit in the
      university's cancer centre was selected as a research site. Nursing records
      extracted from 137 patients (65 for the baseline assessment and 72 for the follow
      up audit) were used to examine nurse compliance with four audit criteria derived
      from best practice guidelines related to the assessment and management of pain.
      We observed a significant improvement in compliance from baseline to follow-up
      for the following criteria: documenting the side effects of opioids (2-83%), use
      of a formalized pain assessment tool (22-75%), and providing education for pain
      assessment and management to patients and caregivers (0-47%). The audit and
      feedback method was applicable to the implementation of clinical practice
      guidelines for cancer pain management. Leadership from both administrative
      personnel and staff nurses working together contributes to the spread of an
      evidence-based practice culture in clinical settings. As it was conducted in a
      single oncology nursing unit and was implemented over a short period of time, the
      results should be carefully interpreted. 

PMID- 24118274
TI  - Sexual selection in a hermaphroditic plant through female reproductive success.
AB  - Sexual selection is well accepted as a mechanism of shaping traits in animals.
      However, whether and how floral traits are sexually selected in hermaphroditic
      plants remains less clear. Here, we use Passiflora incarnata to address how
      floral traits that affect pollination success are selected via female function.
      We manipulated the ecological context by limiting pollination and adding
      resources to expand the phenotypic distribution and alter the intensity of sexual
      selection. Total sexual selection favoured lower style deflexion because of its
      impact on pollen receipt and subsequent seed number. However, total selection on
      style deflexion was not significant, indicating additional selection on style
      deflexion through routes other than mating. Limited pollination and enhanced
      resources were expected to alter the distribution of pollen deposition and seed
      production and therefore intensify the Bateman gradient - the relationship
      between pollen receipt and seed production. Indeed, the Bateman gradient was
      strongest when pollination was limited, suggesting potential for sexual selection
      to influence floral trait evolution under these conditions. Overall, we found
      floral traits may be shaped by sexual selection through female reproductive
      success in this hermaphroditic plant. These results support manipulations to
      enhance the variance in mating as a mechanism to understand patterns of sexual
      selection. 

PMID- 24118275
TI  - Survival and growth of Tetrahymena thermophila in media that are conventionally
      used for piscine and mammalian cells.
AB  - The transfer of Tetrahymena thermophila from normosmotic solutions (~20-80
      mOsm/kg H(2)O) to hyperosmotic solutions (> 290 mOsm/kg H(2)O) was investigated.
      During the first 24 h of transfer from proteose peptone yeast extract (PPYE) to
      either 10 mM HEPES or PPYE with added NaCl to give ~300 mOsm/kg H(2)O, most
      ciliates died in HEPES but survived in PPYE. Supplementing hyperosmotic HEPES or
      PPYE with fetal bovine serum (FBS) enhanced survival. When ciliates were
      transferred from PPYE to a basal medium for vertebrate cells, L-15 (~320 mOsm/kg
      H(2)O), only a few survived the first 24 h but many survived when the starting
      cell density at transfer was high (100,000 cells/ml) or FBS was present. These
      results suggest that nutrients and/or osmolytes in either PPYE or FBS helped
      ciliates survive the switch to hyperosmotic solutions. FBS also stimulated T.
      thermophila growth in normosmotic HEPES and PPYE and in hyperosmotic L-15. In L
      15 with 10% FBS, the ciliates proliferated for several months and could undergo
      phagocytosis and bacterivory. These cell culture systems and results can be used
      to explore how some Tetrahymena species function in hyperosmotic hosts and act as
      opportunistic pathogens of vertebrates.

PMID- 24118277
TI  - Impaired sexual activity in young ischaemic stroke patients: an observational
      study.
AB  - BACKGROUND AND PURPOSE: The present study sought to determine the impact of
      stroke on sexual function and well-being in a cohort of young ischaemic stroke
      patients and identify factors associated with impairment. METHODS: Over a 2-year
      period, all patients aged 60 or under with ischaemic stroke or transient
      ischaemic attack (n = 156) were included. Information on sexual function and well
      being was obtained by means of a paper questionnaire mailed to participants 1
      year after their stroke. Impaired sexual activity (ISA) was defined as a decline
      in sexual function and/or satisfaction. Psychological well-being was evaluated on
      the Hospital Anxiety and Depression Scale (HADS). RESULTS: The response rate was
      67% (n = 104). Thirty of these responders (29%) reported ISA. Patients with ISA
      had a higher HADS score (19.7 vs. 11.2 in patients with no impairment; P <
      0.001), anxiety score (10.0 vs. 6.3; P < 0.001) and depression score (8.7 vs.
      4.8; P < 0.001) and were more likely to have left brain lesions (70% vs. 30%; P <
      0.001) and use angiotensin-converting enzyme (ACE) inhibitors (73% vs. 31%; P <
      0.001) and diuretics (50% vs. 19%; P = 0.003). In a stepwise logistic regression,
      depression (odds ratio 9.1, 95% confidence interval 2.45-33.46; P = 0.001) and
      ACE inhibitor use (odds ratio 6.0, 95% confidence interval 2.11-17.28; P = 0.001)
      were associated with ISA. CONCLUSIONS: Impaired sexual activity was reported by
      almost one-third of younger patients 1 year after ischaemic stroke. Factors
      associated with post-stroke ISA may include specific medications and depression
      rather than the characteristics of the stroke per se.

PMID- 24118278
TI  - Esophageal temperature monitoring during AF ablation: multi-sensor or single
      sensor probe?

PMID- 24118276
TI  - Gentian violet: a 19th century drug re-emerges in the 21st century.
AB  - Gentian violet (GV) has a long and varied history as a medicinal agent.
      Historically used as an antibacterial and antifungal, recent reports have shown
      its utility as an antitypranosomal, antiviral and anti-angiogenic agent. The
      objective of this article is to summarize evidence regarding the efficacy and
      safety of GV use in dermatology. Recent discoveries have found novel targets of
      GV, namely NADPH oxidase in mammalian cells and thioredoxin reductase 2 in
      bacterial, fungal and parasitic cells. These discoveries have expanded the use of
      GV in the 21st century. Given that GV is well tolerated, effective and
      inexpensive, its use in dermatology is predicted to increase. 

PMID- 24118279
TI  - Cervical pregnancy: a report of four cases.
AB  - Various conservative treatments for cervical pregnancy have been reported.
      However, unlike tubal ectopic pregnancy, the treatment of cervical pregnancy has
      not been well established. For patients who desire fertility preservation,
      treatment with methotrexate chemotherapy carries a high success rate for
      preservation of the uterus. When methotrexate is injected i.v. or i.m., expulsion
      of pregnant tissue occasionally takes up to 1 month. In this report, we present
      four cases of cervical pregnancy which were successfully managed by methotrexate
      injection into the bilateral uterine arteries. In cases presenting with massive
      bleeding, embolization of the bilateral uterine arteries was performed. Cervical
      pregnancy was aborted within 8 days safely, and fertility could be preserved
      without harmful side-effects. 

PMID- 24118280
TI  - Microbial screening of unrelated cord blood units in a Chinese cord blood bank.
AB  - BACKGROUND: Given limited sample volume available for sterility testing, optimal
      testing methods and algorithms of cord blood (CB) have not been established
      according to standards. STUDY DESIGN AND METHODS: The volume of CB unit was
      reduced to 20 mL in a closed system. Hetastarch and cryopreservation solution was
      added to the processed CB unit in Class 100 environment. In the routine sterility
      testing, 20 mL of red blood cells (RBC) sample was cultured in aerobic and
      anaerobic culture bottles. In verification post-thaw culture of the final
      product, some of the discarded final product units were also sampled and cultured
      after thaw. All the culture bottles were incubated in the BacT/ALERT 3D system.
      RESULTS: In the routine sterility testing, 139 of 7032 CB units (1.98%) were
      contaminated with microorganism. In 84 of these 139 units (60.4%) only the
      anaerobic bottle was positive. Lactobacillus spp. were the most prevalent
      contaminant. Sixty-two discarded CB stem cell units were recultured after thaw.
      Of these, 10 of 48 units with a positive culturing of RBC sample were negative in
      the post-thaw reculture. One of 14 units with negative culturing of RBC sample
      was contaminated with Bifidobacterium breve in special verification test.
      CONCLUSION: Our study demonstrates the predominant organisms implicated in CB
      microbial contamination were part of the human intestinal and vaginal flora. The
      larger sample volume and anaerobic culture would significantly increase the
      detection rate of microbial contaminated CB. We also found that potential
      transfusion-transmitted bacterial infection risk still existed in final product
      although microbial screening was performed.

PMID- 24118281
TI  - Endoscopic ultrasound-guided antegrade diathermic dilation followed by self
      expandable metallic stent placement for anastomotic stricture after
      hepaticojejunostomy (with video).

PMID- 24118282
TI  - What do the terms wellness and wellbeing mean in dietary practice: an exploratory
      qualitative study examining women's perceptions.
AB  - BACKGROUND: Wellness and wellbeing are terms associated with health within
      dietetic discourse. More broadly, these terms are found in social discourse as
      represented in food and nutrition consumer communications. With the increasing
      requirement for evidence-based healthcare, there is an imperative to understand
      whether these terms are meaningful to individuals typically targeted for
      nutrition interventions and whether there are any implications for dietetic
      education. METHODS: To explore the understanding of these terms, eight semi
      structured focus groups were conducted with 32 female participants (age range 23
      79 years) who were actively engaged in managing their health. Overall
      understanding of the terms, factors that impacted perceptions and any
      relationships with food behaviour were investigated with the groups. Group
      discussions were transcribed verbatim and each transcript was examined by two
      researchers. Inductive analysis linking codes into main thematic categories was
      conducted using the constant comparison approach across the full data set.
      RESULTS: Wellness and wellbeing were identified as meaningful terms associated
      with health. A theoretical framework of wellness and wellbeing reflecting these
      meanings was developed linking four dominant thematic areas. These were Desired
      outcomes (most sought after result); Taking control (self management strategies);
      Internal influences (various personal inner factors influencing behaviours); and
      External influences (plethora of peripheral factors influencing behaviours).
      CONCLUSIONS: Wellness and wellbeing are terms that are relevant and aspirational
      for individuals typically targeted for nutrition intervention. A theoretical
      framework of dominant areas of influence on notions of wellness and wellbeing was
      identified. This theoretical framework is worthy of further research to determine
      usefulness and effectiveness in dietetic practice settings.

PMID- 24118283
TI  - Lactobacillus brevis CD2 inhibits Prevotella melaninogenica biofilm.
AB  - OBJECTIVE: To evaluate the ability of the probiotic strain Lactobacillus brevis
      CD2 to inhibit the opportunistic anaerobe Prevotella melaninogenica (PM1), a well
      known causative agent of periodontitis. MATERIALS AND METHODS: The inhibitory
      effect of Lactobacillus CD2 on Prevotella PM1 biofilm was assessed both by
      exposing the anaerobe to the supernatant of the probiotic strain and by growing
      the two strains to obtain single or mixed biofilms. The inhibitory effect of CD2
      on PM1 was also checked by the agar overlay method. RESULTS: The development of
      PM1 biofilm was strongly affected (56% decrease in OD value) by the CD2
      supernatant after 96 h. A dose-dependent biofilm reduction was also observed at
      1/10 and 1/100 dilutions of supernatant. Confocal microscopy on the mixed
      biofilms revealed the ability of CD2 to prevail on PM1, greatly reducing the
      biofilm of the latter. CONCLUSIONS: It has been hypothesized a multifactorial
      nature of the inhibition mechanism, the strong adherence ability of CD2 strain
      together with the released metabolites presumably contributing to the reduction
      in the PM1 biofilm detected by confocal microscopy.

PMID- 24118284
TI  - Performance of transverse tripoles vs. longitudinal tripoles with anode
      intensification (AI) in spinal cord stimulation: computational modeling study.
AB  - OBJECTIVE: In spinal cord stimulation, anodes tend to have a strong effect over
      the area of dorsal column (DC) activation, when configured as both longitudinal
      guarded cathodes (LGCs) and transverse tripoles (TTs). Inclusion of a small
      spacing step (LGC+) in the center-center (C-C) spacing of the LGC can be an
      efficient method to study the local effects around the electrode. The primary aim
      of this computer modeling study is to investigate if enhanced DC recruitment is
      achieved when anodal currents in TT and LGC combinations (both LGC and LGC+) are
      increased up to 30% with respect to the cathodal current. Secondly, the merits of
      anodal intensification (AI) are evaluated by comparing the DC recruitment areas
      (S(RA)) and energy consumption (EDT ) of LGC+ with AI, against stimulation using
      an LGC without AI. MATERIALS AND METHODS: The commercially available LGC and
      LGC+, with 4.0 and 4.5 mm C-C, respectively, were modeled on a single
      percutaneous lead at the low-thoracic vertebral region (T10-T12). Transverse
      tripolar stimulation (TTS) was modeled on triple percutaneous leads. RESULTS: TTS
      with 10% AI recruited a smaller S(RA) as compared with TTS with no AI. AI of LGC
      and LGC+ resulted in increasing SRAs respectively to that of LGC and LGC+ without
      AI. Also, AI of LGC+ recruited a larger S(RA) and usage range (UR) at lower E(DT)
      compared with that of LGC without AI. CONCLUSIONS: AI of TTS is not advantageous.
      LGC and LGC+ with AI allow additional DC stimulation, which may increase the
      likelihood of activating fibers inaccessible with conventional programming. LGC+
      with AI can be more efficient than LGCs without AI, as a larger SRA and UR is
      achieved at lower EDT .

PMID- 24118286
TI  - Transdiaphragmatic hepatic and pulmonary abscess attributed to ileal
      diverticulitis in a horse.

PMID- 24118285
TI  - Reproductive experience alters neural and behavioural responses to acute
      oestrogen receptor alpha activation.
AB  - Reproductive experience (i.e. parturition and lactation) leads to persistent
      alterations in anxiety-like behaviour that are influenced by the oestrous cycle.
      We recently found that repeated administration of the selective oestrogen
      receptors (ER)alpha agonist propyl-pyrazole triol (PPT) results in anxiolytic
      like behaviours on the elevated plus maze (EPM) in primiparous (but not
      nulliparous) female rats. The present study examined the effects of the acute
      administration of PPT on EPM behaviour in primiparous and aged-matched,
      nulliparous female rats. In addition, corticosterone secretion, corticotrophin
      releasing hormone (CRH) gene expression and expression of the immediate early
      gene product Fos in the paraventricular nucleus (PVN) and amygdala were measured
      either after EPM testing or in home cage controls. Acute PPT administration
      significantly modified EPM behaviour as a function of reproductive experience,
      with nulliparous females tending toward increased anxiety-like behaviours and
      primiparous females tending toward decreased anxiety-like behaviours. In home
      cage controls, PPT increased corticosterone secretion in all females; however,
      both vehicle- and PPT-treated, primiparous females had reduced corticosterone
      levels compared to their nulliparous counterparts. Significant effects of PPT on
      CRH mRNA within the PVN were observed after the administration of PPT but only in
      primiparous females tested on the EPM. PPT also increased Fos expression within
      the PVN of EPM-exposed females; however, both vehicle- and PPT-treated
      primiparous females had reduced Fos expression compared to nulliparous females.
      In the amygdala, PPT increased Fos immunoreactivity in the central but not the
      medial or basolateral amygdala, although these effects were only observed in home
      cage females. Additionally, both vehicle- and PPT-treated home cage, primiparous
      females had increased Fos in the central nucleus of the amygdala compared to
      nulliparous controls. Overall, these data demonstrate that reproductive
      experience alters the behavioural response to acute ERalpha activation. Moreover,
      the findings suggest that central regulation of the hypothalamic-adrenal
      pituitary axis is modified as a consequence of reproductive experience. 

PMID- 24118287
TI  - PVC flooring at home and development of asthma among young children in Sweden, a
      10-year follow-up.
AB  - The incidence of asthma and allergy has increased throughout the developed world
      over the past decades. During the same period of time, the use of industrial
      chemicals such as phthalates, commonly used as plasticizers in polyvinylchloride
      (PVC) flooring material, has increased. The aim of this study was to investigate
      whether PVC flooring in the home of children in the age of 1-5 years is
      associated with the development of asthma in 5- and 10-year follow-up
      investigations (n = 3228). Dampness in Buildings and Health Study (DBH Study)
      commenced in 2000 in Varmland, Sweden. The current analyses included subjects who
      answered all baseline and follow-up questionnaires. Logistic regression analyses
      were applied to questionnaire results. Children who had PVC floorings in the
      bedroom at baseline were more likely to develop doctor-diagnosed asthma during
      the following 10-year period when compared with children living without. There
      were indications that PVC flooring in the parents' bedrooms was strongly
      associated with the new cases of doctor-diagnosed asthma when compared with
      child's bedroom. Our results suggest that PVC flooring exposure during pregnancy
      could be a critical period in the development of asthma in children at a later
      time; prenatal exposure and measurements of phthalate metabolites should be
      included in the future. PRACTICAL IMPLICATIONS: This study has found that PVC
      flooring material in early life was related to incidence of asthma during the
      following 10 years when compared with other flooring materials and especially
      when comparing with wood flooring type.The study has further indicated that PVC
      flooring in the parents' bedroom (proxy for prenatal exposure) was more
      associated with the development of asthma than PVC in the child's bedroom was.
      Our results suggest that PVC flooring exposure during pregnancy could be a
      critical period in the development of asthma in children at a later time. In
      future prospective cohort study, prenatal exposure and measurements of phthalate
      metabolites should be included.

PMID- 24118288
TI  - Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis.
AB  - Recent evidence suggests that oxidative stress contributes to the pathogenesis of
      prostate cancer. The present study focused on the effect of apocynin, an
      inhibitor of NADPH oxidase, on prostate carcinogenesis using the transgenic rat
      for adenocarcinoma of prostate (TRAP) model. There were no toxic effects with
      apocynin treatment. The percentages and numbers of carcinomas in both the ventral
      and lateral prostate were significantly reduced by apocynin treatment, with dose
      dependence. Reduction of reactive oxygen species by apocynin was confirmed by
      immunohistochemistry of 8-OHdG and dihydroethidium staining. Positivity of Ki67
      was significantly reduced by apocynin treatment, and downregulation of clusterin
      expression, as well as inactivation of the MEK-ERK1/2 pathway, was a feature of
      the apocynin treated groups. In human prostate cancer cell line LNCaP, apocynin
      also inhibited reactive oxygen species production and blocked cell growth by
      inducing G0/G1 arrest with downregulation of clusterin and cyclin D1. These data
      suggest that apocynin possesses chemopreventive potential against prostate
      cancer. 

PMID- 24118289
TI  - Laminin-5 gamma 2 chain expression is associated with intensity of tumor budding
      and density of stromal myofibroblasts in oral squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent
      cancers worldwide. Laminin-5 gamma 2 chain (laminin-5 gamma2) is a protein
      associated to a migratory phenotype in epithelial neoplastic cells. Stromal
      myofibroblasts also play a significant role in tumor invasion, due to its ability
      to modify the extracellular matrix. Tumor budding is a morphologic marker of
      tumor invasion. The aim of this study was to evaluate the expression of laminin-5
      gamma2 in OSCC and its association with intensity of tumor budding and density of
      stromal myofibroblasts. METHODS: Paraffin-embedded archival samples of 57 OSCC
      patients were evaluated. Immunohistochemistry was employed to detect laminin-5
      gamma2, alpha smooth muscle actin (marker of stromal myofibroblasts), and
      multicytokeratin (to identify OSCC cells in tumor budding evaluation). Laminin-5
      gamma2 expression and its association with intensity of tumor budding and density
      of stromal myofibroblasts were analyzed. Association among intensity of tumor
      budding and density of stromal myofibroblasts was also evaluated. RESULTS: Higher
      laminin-5 gamma2 expression was associated with high-intensity tumor budding (P <
      0.05) and with higher density of stromal myofibroblasts (P < 0.05). Moreover,
      high-intensity tumor budding was associated with higher density of stromal
      myofibroblasts (P < 0.05). CONCLUSIONS: In OSCC, higher laminin-5 gamma2
      expression is associated with high-intensity tumor budding and with higher
      density of stromal myofibroblasts, suggesting that this expression is related to
      the establishment of an invasive phenotype of neoplastic cells and a permissive
      environment for tumor invasion in this neoplasia.

PMID- 24118290
TI  - Estimation of the dispersal of a major pest of maize by cline analysis of a
      temporary contact zone between two invasive outbreaks.
AB  - Dispersal is a key factor in invasion and in the persistence and evolution of
      species. Despite the importance of estimates of dispersal distance, dispersal
      measurement remains a real methodological challenge. In this study, we
      characterized dispersal by exploiting a specific case of biological invasion, in
      which multiple introductions in disconnected areas lead to secondary contact
      between two differentiated expanding outbreaks. By applying cline theory to this
      ecological setting, we estimated sigma, the standard deviation of the parent
      offspring distance distribution, of the western corn rootworm, Diabrotica
      virgifera virgifera, one of the most destructive pests of maize. This species is
      currently invading Europe, and the two largest invasive outbreaks, in northern
      Italy and Central Europe, have recently formed a secondary contact zone in
      northern Italy. We identified vanishing clines at 12 microsatellite loci
      throughout the contact zone. By analysing both the rate of change of cline slope
      and the spatial variation of linkage disequilibrium at these markers, we obtained
      two sigma estimates of about 20 km/generation(1/2). Simulations indicated that
      these estimates were robust to changes in dispersal kernels and differences in
      population density between the two outbreaks, despite a systematic weak bias.
      These estimates are consistent with the results of direct methods for measuring
      dispersal applied to the same species. We conclude that secondary contact
      resulting from multiple introductions is very useful for the inference of
      dispersal parameters and should be more widely used in other species.

PMID- 24118291
TI  - Local control of rhino-orbito-cerebral mucormycosis dramatically impacts
      survival.
AB  - Surgery and antifungals are the reference standard for rhino-orbito-cerebral
      mucormycosis (ROCM) treatment. The impact of local control on survival of 22
      consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively,
      with or without local control (p <0.0001). Hence, repeated surgical procedures
      are recommended to achieve local control of ROCM. 

PMID- 24118293
TI  - Value of serial heart rate variability measurement for prediction of appropriate
      ICD discharge in patients with heart failure.
AB  - INTRODUCTION: Decreased heart rate variability (HRV) is associated with adverse
      outcomes in patients with heart failure. Our objective was to examine whether
      decreased HRV predicts appropriate implantable cardioverter defibrillator (ICD)
      shocks. METHODS AND RESULTS: In 105 patients with a Boston Scientific Contak
      Renewal, Cognis or Energen device implanted for either primary (73.3%) or
      secondary prevention (26.7%), time domain HRV variables standard deviation of
      averages of normal beat-to-beat interval (SDANN) and footprint percentage (FPP)
      were collected at baseline and during follow-up. In case of appropriate shock,
      HRV before shock was assessed. Using time-dependent Cox regression models, the
      relation between median-based dichotomized SDANN or FFP and appropriate shock was
      investigated. Baseline characteristics between patients with or without shocks
      were similar, with exception of secondary prevention patients using more often
      antiarrhythmic drugs. During follow-up (median 451, IQR 202-1,460 days),
      appropriate shocks occurred in 20 (19%) patients. SDANN and FPP did not differ
      significantly at baseline between patients with or without shocks (respectively,
      P = 0.18 and P = 0.78). However, time-dependent Cox regression analysis showed a
      trend that patients were at lower risk for appropriate shock (SDANN: HR 0.43, 95%
      CI [0.18-1.05], P = 0.06 and FPP: HR 0.49, 95% CI [0.20-1.20], P = 0.12) when HRV
      values were above median baseline value during follow-up. CONCLUSIONS: These
      results imply that HRV could be an independent predictor for appropriate shocks.
      Therefore, low HRV could be of additional use in predicting imminent appropriate
      shocks and could possibly guide concomitant medical therapy.

PMID- 24118294
TI  - The oxidative costs of territory quality and offspring provisioning.
AB  - The costs of reproduction are an important constraint that shapes the evolution
      of life histories, yet our understanding of the proximate mechanism(s) leading to
      such life-history trade-offs is not well understood. Oxidative stress is a strong
      candidate measure thought to mediate the costs of reproduction, yet empirical
      evidence supporting that increased reproductive investment leads to oxidative
      stress is equivocal. We investigated whether territory quality and offspring
      provisioning increase oxidative stress in male snow buntings (Plectrophenax
      nivalis) using a repeated sampling design. We show that arrival oxidative stress
      is not a constraint on territory quality or the number of offspring fledged.
      Nevertheless, owners of higher-quality territories experienced an oxidative cost,
      with this cost increasing more rapidly in younger males. Males that provisioned
      offspring at a high rate also experienced increased oxidative stress. Together,
      these findings support the potential role of oxidative stress in mediating life
      history trade-offs. Future work should consider that reproductive workload is not
      limited to offspring care, and other activities - including territory defence -
      may contribute significantly to the costs of reproduction. 

PMID- 24118292
TI  - Psychiatric comorbidity in treatment-seeking substance use disorder patients with
      and without attention deficit hyperactivity disorder: results of the IASP study.
AB  - AIMS: To determine comorbidity patterns in treatment-seeking substance use
      disorder (SUD) patients with and without adult attention deficit hyperactivity
      disorder (ADHD), with an emphasis on subgroups defined by ADHD subtype, taking
      into account differences related to gender and primary substance of abuse.
      DESIGN: Data were obtained from the cross-sectional International ADHD in
      Substance use disorder Prevalence (IASP) study. SETTING: Forty-seven centres of
      SUD treatment in 10 countries. PARTICIPANTS: A total of 1205 treatment-seeking
      SUD patients. MEASUREMENTS: Structured diagnostic assessments were used for all
      disorders: presence of ADHD was assessed with the Conners' Adult ADHD Diagnostic
      Interview for DSM-IV (CAADID), the presence of antisocial personality disorder
      (ASPD), major depression (MD) and (hypo)manic episode (HME) was assessed with the
      Mini International Neuropsychiatric Interview-Plus (MINI Plus), and the presence
      of borderline personality disorder (BPD) was assessed with the Structured
      Clinical Interview for DSM-IV Axis II (SCID II). FINDINGS: The prevalence of DSM
      IV adult ADHD in this SUD sample was 13.9%. ASPD [odds ratio (OR) = 2.8, 95%
      confidence interval (CI) = 1.8-4.2], BPD (OR = 7.0, 95% CI = 3.1-15.6 for
      alcohol; OR = 3.4, 95% CI = 1.8-6.4 for drugs), MD in patients with alcohol as
      primary substance of abuse (OR = 4.1, 95% CI = 2.1-7.8) and HME (OR = 4.3, 95% CI
      = 2.1-8.7) were all more prevalent in ADHD(+) compared with ADHD(-) patients (P <
      0.001). These results also indicate increased levels of BPD and MD for alcohol
      compared with drugs as primary substance of abuse. Comorbidity patterns differed
      between ADHD subtypes with increased MD in the inattentive and combined subtype
      (P < 0.01), increased HME and ASPD in the hyperactive/impulsive (P < 0.01) and
      combined subtypes (P < 0.001) and increased BPD in all subtypes (P < 0.001)
      compared with SUD patients without ADHD. Seventy-five per cent of ADHD patients
      had at least one additional comorbid disorder compared with 37% of SUD patients
      without ADHD. CONCLUSIONS: Treatment-seeking substance use disorder patients with
      attention deficit hyperactivity disorder are at a very high risk for additional
      externalizing disorders.

PMID- 24118295
TI  - Deficient cytokine expression and neutrophil oxidative burst contribute to
      impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds.
AB  - Diabetic patients exhibit dysregulated inflammatory and immune responses that
      predispose them to chronic wound infections and the threat of limb loss. The
      molecular underpinnings responsible for this have not been well elucidated,
      particularly in the setting of wound biofilms. This study evaluates host
      responses in biofilm-impaired wounds using the TallyHo mouse, a clinically
      relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll
      like receptor (TLR) expression were noted in unwounded skin or noninoculated
      wounds of diabetic and wild-type mice. However, diabetic biofilm-containing
      wounds had significantly less TLR 2, TLR 4, interleukin-1beta, and tumor necrosis
      factor-alpha expression than wild-type wounds with biofilm (all p < 0.001). Both
      groups had similar bacterial burden and neutrophil infiltration after development
      of biofilms at 3 days postwounding, but diabetic wounds had significantly less
      neutrophil oxidative burst activity. This translated into a log-fold greater
      bacterial burden and significant delay of wound epithelization for biofilm
      impaired diabetic wounds at 10 days postwounding. These results suggest that
      impaired recognition of bacterial infection via the TLR pathway leading to
      inadequate cytokine stimulation of antimicrobial host responses may represent a
      potential mechanism underlying diabetic susceptibility to wound infection and
      ulceration.

PMID- 24118296
TI  - Factors influencing patient satisfaction with antimuscarinic treatment of
      overactive bladder syndrome: results of a real-life clinical study.
AB  - OBJECTIVES: To investigate patient satisfaction with antimuscarinic treatment of
      overactive bladder syndrome, and to identify factors having a significant
      influence on satisfaction. METHODS: A cross-sectional questionnaire survey was
      carried out to assess treatment satisfaction among male and female patients with
      overactive bladder (age >=20 years) in the Hokuriku district of Japan. The
      overactive bladder symptom scores, treatment efficacies, adverse events (dry
      mouth and constipation), and patient satisfaction scores were investigated and
      compared among patients using different antimuscarinic therapeutics. RESULTS: In
      total, 977 survey respondents (52.6% men; mean age 73.6 years) received
      antimuscarinic treatment. The mean overactive bladder symptom score of these
      patients was 6.17; in addition, 32.3% patients were satisfied with their
      treatment, but 33.1% were dissatisfied. Factors having a significant influence on
      treatment satisfaction were sex (men were less satisfied), efficacy, adverse
      events and the overactive bladder symptom score. Constipation negatively
      influenced patient satisfaction to a greater extent than did dry mouth. Patient
      satisfaction varied according to the drug used. Constipation was less severe with
      the immediate-release-type agents (imidafenacin and oxybutynin) than with the
      extended-release-type (propiverine, solifenacin or tolterodine). CONCLUSIONS:
      Just one-third of Japanese Hokuriku patients with overactive bladder seem to be
      satisfied with their antimuscarinic treatment. Patient satisfaction is impaired
      by poor efficacy and the presence of adverse events; furthermore, constipation
      should be recognized as an adverse event that negatively influences patient
      satisfaction to a greater extent than dry mouth. Patient satisfaction differs
      according to the antimuscarinic agent used, with higher patient satisfaction
      being associated with less severe constipation.

PMID- 24118297
TI  - A qualitative study on the roles and responsibilities of nurse consultants in
      Hong Kong.
AB  - This study aims to explore the roles and responsibilities of seven newly
      appointed nurse consultants (NCs) in various clinical specialties in Hong Kong as
      a pioneer project. Qualitative approaches using direct observation and semi
      structured interviews were adopted with two full-day observations on the seven
      NCs plus 56 semi-structured interviews of NCs, nurses, doctors and patients. Five
      major NCs' roles and responsibilities had been identified, namely providing
      expert practice, initiating service development, leading education, guiding
      continuous quality improvement (CQI) and conducting research and providing
      evidence-based practice. The seven NCs within this study have by and large
      achieved building professional excellence, respect and trust within their own
      spheres. It is strongly recommended that the NC post be formally established in
      the new Nurses Career Structure to enable expert clinical nurses to develop a
      clinical career to contribute to service and patient care to its maximum. 

PMID- 24118298
TI  - Response to letter on tangential shave removal of basal cell carcinoma.

PMID- 24118299
TI  - Men's reflections on participating in cancer rehabilitation: a systematic review
      of qualitative studies 2000-2013.
AB  - This paper aims to report on a systematic review of qualitative studies on men's
      reflections on participating in cancer rehabilitation. Nine databases were
      systematically searched to identify qualitative papers published between 2000 and
      2013. Papers were selected by pre-defined inclusion criteria and subsequently
      critically appraised. Key themes were extracted and synthesised. Fifteen papers
      were selected and represented. Four central themes were identified in the
      analytical process: 'changed life perspective', 'the masculinity factor', 'a
      desire to get back to normal' and 'the meaning of work'. Six peripheral themes
      were identified: 'the meaning of context', 'music', 'physical training',
      'religion', 'humour' and 'the unmentionable'. The themes were synthesised into an
      integrative model representing men's reflections on participating in cancer
      rehabilitation. We conclude that existing qualitative literature offers insight
      into men's reflections on cancer rehabilitation and highlights the
      interrelationship between men's reflections on their changed life perspective,
      masculinity, orientation towards a normal life and getting back to work. Further
      research-based knowledge is needed to explore (1) the underlying causes and
      patterns of the men's needs, preferences and choices in rehabilitation; and (2)
      the health professional perspective on male cancer rehabilitation. 

PMID- 24118300
TI  - Early changes in scores of chronic damage on transplant kidney protocol biopsies
      reflect donor characteristics, but not future graft function.
AB  - The amount of irreversible injury on renal allograft biopsy predicts function,
      but little is known about the early evolution of this damage. In a single-center
      cohort, we examined the relationship between donor-, recipient-, and
      transplantation-associated factors and change in a morphometric index of chronic
      damage (ICD) between protocol biopsies performed at implantation and at 2-3
      months. We then investigated whether early delta ICD predicted subsequent
      biochemical outcomes. We found little evidence to support differences between the
      study group, who had undergone serial biopsies, and a contemporaneous control
      group, who had not. In allografts with serial biopsies (n = 162), there was an
      increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post
      transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors
      was independently associated with smaller early post-transplant increases in ICD.
      There was no evidence for a difference in delta ICD between donation after
      cardiac death vs. donation after brain death, nor association with length of cold
      ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD
      after three months did not predict allograft function at one yr. These findings
      suggest that graft damage develops shortly after transplantation and reflects
      donor factors, but does not predict future biochemical outcomes.

PMID- 24118301
TI  - Inclusion of CYP3A5 genotyping in a nonparametric population model improves
      dosing of tacrolimus early after transplantation.
AB  - Following organ engraftment, initial dosing of tacrolimus is based on recipient
      weight and adjusted by measured C(0) concentrations. The bioavailability and
      elimination of tacrolimus are affected by the patients CYP3A5 genotype.
      Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype
      prior to transplantation are lacking. A nonparametric population model was
      developed for tacrolimus in renal transplant recipients. Data from 99 patients
      were used for model development and validation. A three-compartment model with
      first-order absorption and lag time from the dosing compartment described the
      data well. Clearances and volumes of distribution were allometrically scaled to
      body size. The final model included fat-free mass, body mass index, hematocrit,
      time after transplantation, and CYP3A5 genotype as covariates. The bias and
      imprecision were 0.35 and 1.38, respectively, in the external data set. Patients
      with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability.
      Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3-4
      tacrolimus concentrations were known. After this, a model without CYP3A5 genotype
      predicted just as well. The present models seem applicable for clinical
      individual dose predictions but need a prospective evaluation.

PMID- 24118302
TI  - Deranged epidermal differentiation in kl/kl mouse and the effects of betaKlotho
      siRNA on the differentiation of HaCaT cells.
AB  - Mice deficient in the klotho gene (kl/kl mice) display the phenotypes of human
      ageing. We found that the expression of epidermal differentiation-associated
      factors (keratin 1, keratin 10, filaggrin and loricrin) was lower in the skin of
      kl/kl mice than that of wild-type mice. In vitro experiments showed that the
      expression of betaKlotho, a family of klotho gene-encoded protein, was induced
      concomitantly with the differentiation of an immortalized human epidermal
      keratinocyte cell line (HaCaT cells) when they were cultured in an air-liquid
      interface. betaKlotho knockdown by small interfering ribonucleic acid suppressed
      the expression of the above differentiation-associated factors in HaCaT cells.
      betaKlotho small interfering ribonucleic acid increased the expression of keratin
      14, which is expressed in mitotically active basal layer cells, and activated
      p44/p42 mitogen-activated protein kinase in the HaCaT cells grown in the air
      liquid interface. These findings suggest that the epidermal differentiation is
      deranged in kl/kl mice, and betaKlotho is required for the differentiation of
      human epidermal keratinocytes. 

PMID- 24118303
TI  - Amplicon pyrosequencing reveals the soil microbial diversity associated with
      invasive Japanese barberry (Berberis thunbergii DC.).
AB  - The soil microbial community acts as a reservoir of microbes that directly
      influences the structure and composition of the aboveground plant community,
      promotes plant growth, increases stress tolerance and mediates local patterns of
      nutrient cycling. Direct interactions between plants and rhizosphere-dwelling
      microorganisms occur at, or near, the surface of the root. Upon introduction and
      establishment, invasive plants modify the soil microbial communities and soil
      biochemistry affecting bioremediation efforts and future plant communities. Here,
      we used tag-encoded FLX amplicon 454 pyrosequencing (TEFAP) to characterize the
      bacterial and fungal community diversity in the rhizosphere of Berberis
      thunbergii DC. (Japanese barberry) from invasive stands in coastal Maine to
      investigate effects of soil type, soil chemistry and surrounding plant cover on
      the soil microbial community structure. Acidobacteria, Actinobacteria,
      Proteobacteria and Verrucomicrobia were the dominant bacterial phyla, whereas
      fungal communities were comprised mostly of Ascomycota and Basidiomycota phyla
      members, including Agaricomycetes and Sordariomycetes. Bulk soil chemistry had
      more effect on the bacterial community structure than the fungal community. An
      effect of geographic location was apparent in the rhizosphere microbial
      communities, yet it was less significant than the effect of surrounding plant
      cover. These data demonstrate a high degree of spatial variation in the
      rhizosphere microbial communities of Japanese barberry with apparent effects of
      soil chemistry, location and canopy cover on the microbial community structure. 

PMID- 24118304
TI  - WRKY46 functions as a transcriptional repressor of ALMT1, regulating aluminum
      induced malate secretion in Arabidopsis.
AB  - Aluminum (Al) toxicity is the major limiting factor for crop production on acid
      soils, but the transcriptional regulation of Al tolerance genes is largely
      unknown. Here, we found that the expression of a WRKY domain-containing
      transcription factor WRKY46 is inhibited by Al and expressed in root stele,
      whereas the expression of ALMT1, which encodes a malate efflux transporter, is
      induced by Al stress and spatially co-localized with WRKY46 in root stele,
      indicating the possible interaction between WRKY46 and ALMT1 in Arabidopsis.
      Mutation of WRKY46 by T-DNA insertion leads to better root growth under Al
      stress, and lower root Al content compared with the wild-type Col-0. The wrky46
      mutant shows increased root malate secretion, which is consistent with the higher
      ALMT1 expression in the mutant. Transient expression analysis using truncated
      promoter of ALMT1 showed that ALMT1 expression can be inhibited by WRKY46 in
      tobacco leaves. The yeast one-hybrid assay and ChIP-qPCR analysis revealed that
      WRKY46 directly binds to ALMT1 promoter through specific W-boxes. Taken together,
      we demonstrated that WRKY46 is a negative regulator of ALMT1, mutation of WRKY46
      leads to increased malate secretion and reduced Al accumulation in root apices,
      and thus confers higher Al resistance. 

PMID- 24118305
TI  - Transcription profile of chemokine receptors, cytokines and cytotoxic markers in
      peripheral blood of dogs with epitheliotropic cutaneous lymphoma.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common form of canine
      epitheliotropic cutaneous lymphoma, which is characterized by the accumulation of
      neoplastic CD8(+) T cells. Given that multifocal skin lesions are commonly seen
      in MF, neoplastic lymphocytes may actively migrate into the blood circulation.
      HYPOTHESIS/OBJECTIVES: Cytotoxic T cells with a skin-homing phenotype could be
      increased in the blood circulation of dogs with MF. ANIMALS: Ten dogs with MF and
      10 age-matched healthy dogs were included. METHODS: The transcription levels of
      chemokine receptors, cytokines and cytotoxic markers in peripheral blood of dogs
      with MF were quantified by real-time RT-PCR. RESULTS: The dogs with MF had lower
      transcription levels of chemokine receptors associated with skin homing (CCR4),
      epitheliotropism (CXCR3), lymph node homing (CCR7), a type-1 cytokine (LT-alpha)
      and cytotoxic markers (perforin and granzyme B) in the circulation than healthy
      control dogs (P < 0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: The present results
      suggest that the number of peripheral cytotoxic T cells with a skin-homing
      phenotype could be decreased in the peripheral blood of dogs with MF, which might
      be due to the sequestration of cytotoxic T cells in the lesional skin.

PMID- 24118306
TI  - Total atrial conduction time assessed by tissue doppler imaging (PA-TDI Interval)
      to predict early recurrence of persistent atrial fibrillation after successful
      electrical cardioversion.
AB  - BACKGROUND: The aim of this study was to investigate whether total atrial
      conduction time (TACT) assessed via tissue Doppler imaging (PA-TDI interval) can
      identify patients with early recurrent atrial fibrillation (ERAF) after
      successful direct-current electrical cardioversion (CV) of persistent atrial
      fibrillation (persPAF). METHODS AND RESULTS: A total of 54 patients without
      antiarrhythmic drug medication (mean +/- SD: 66 +/- 10.4 years; 33% women) with
      persPAF and successful CV were enrolled between May 2012 and May 2013. TACT was
      measured 6 hours after successful CV in the left atrium by tissue Doppler imaging
      (PA-TDI interval). ERAF was determined via Holter-electrocardiogram over a period
      of 7 days after CV. Receiver opearting characteristic analysis was used to
      determine an optimal cutoff value of PA-TDI interval for prognosis of ERAF. Based
      on this result, recurrence-free survival was assessed with Mantel-Haenszel's log
      rank test. ERAF occurred in 23 patients (43%). PA-TDI interval was longer in
      patients with ERAF compared to those who maintained sinus rhythm (mean +/- SD:
      163.5 +/- 11.1 vs 132.3 +/- 11.2 milliseconds; P < 0.00001). At the cutoff value
      of 152 milliseconds, PA-TDI interval sensitivity and specificity related to ERAF
      were 87% and 100%, respectively. CONCLUSION: Measuring PA-TDI interval may help
      to predict ERAF after successful CV in patients with persAF.

PMID- 24118307
TI  - Developmental competence of human embryos derived from in vitro maturation of
      immature oocytes retrieved during cesarean section.
AB  - AIM: To investigate the developmental competence of human embryos that originated
      from in vitro matured oocytes retrieved during cesarean section. METHODS:
      Immature oocytes were collected from 95 pregnant women, who underwent cesarean
      section at Buddhachinaraj Hospital Medical School and consented to participate in
      the study. Retrieved oocytes were cultured in blastocyst medium supplemented with
      75 IU/L of human menopausal gonadotropin. Oocyte maturation was assessed at 30
      and 48 h after culture. In vitro matured oocytes were inseminated by
      intracytoplasmic sperm injection and cultured up to 144 h. The fertilization,
      cleavage and blastocyst formation rates were observed. RESULTS: Maturation rate
      of oocytes after 30 h of culture was 67.9% compared with 13.1% at 48 h (P <
      0.0001). Insemination of oocytes in both groups resulted in similar
      fertilization, cleavage and blastocyst formation rates. CONCLUSION: A large
      proportion of oocytes retrieved at the time of cesarean section exhibited the
      capacity to undergo maturation in vitro. They can be fertilized and developed
      into good-quality blastocyst stage.

PMID- 24118308
TI  - A new der(1;7)(q10;p10) leading to a singular 1p loss in a case of glioblastoma
      with oligodendroglioma component.
AB  - The combined 1p-/19q- deletions in oligodendrogliomas originate from
      translocation between both chromosomes. In the few cases of oligoastrocytomas and
      glioblastomas with an oligodendroglioma component (GBMO) where only 1p deletion
      was described, the origin remains unknown. We report the first case of GBMO, in
      which a single 1p deletion was detected and was linked to a translocation between
      chromosomes 1 and 7. Fresh surgical specimens were collected during surgery and
      the samples were used for cell culture, touch preparation smear slides (TP
      slides) and DNA extraction. Peripheral venous blood was also collected from the
      patient. G-banding using Trypsin and stained with Giemsa (GTG) banding and
      karyotyping were performed and 1p-/19q-, TP53, PTEN and c-MYC were analyzed by
      fluorescent in situ hybridization (FISH). Multicolor FISH (mFISH) and
      microsatellites analyses were also performed to complete the investigation. Three
      dimensional quantitative FISH (3D-QFISH) of telomeres was performed on nuclei
      from TP slides and analyzed using TeloView(TM) to determine whether the 3D
      telomere profile as an assessment of telomere dysfunction and a characterization
      of genomic instability could predict the disease aggressiveness. An unbalanced
      chromosomal translocation was found in all metaphases and confirmed by mFISH. The
      karyotype of the case is: 50~99,XXX, +der(1;7)(q10;p10),inc[47] The derivative
      chromosome was found in all 47 analyzed cells, but the number of derivatives
      varied from one to four. There was neither imbalance in copy number for genes
      TP53 and PTEN, nor amplification of c-MYC gene. We did not find loss of
      heterozygosity with analysis of microsatellite markers for chromosomes 1p and 19q
      in tumor cells. The 3D-telomere profile predicted a very poor prognostic and
      short-term survival of the patient and highlights the potential clinical power of
      telomere signatures as a solid biomarker of GBMO. Furthermore, this translocation
      between chromosomes 1 and 7 led to a singular 1p deletion in this GBMO and may
      generate the 1p and 7q deletions. 

PMID- 24118309
TI  - Voices of care for adults with disabilities and/or mental health issues in
      Western Canada: what do families and agencies need from each other?
AB  - Our purpose in this paper is to report on the frustrations and unmet needs of
      paid, formal caregivers and unpaid, family caregivers who together provide care
      to adults with disabilities and/or mental health issues. We conducted eight focus
      group interviews between November 2010 and June 2011 in two large, urban centres
      and one smaller centre in Western Canada. Four of our focus groups were with
      family members including adults with disabilities and/or mental health issues,
      their parents and their siblings, and four were with representatives from
      agencies providing support and services to adults with disabilities and/or mental
      health issues and their families. Data were collected from 23 family members and
      24 agency representatives who responded to questions about successes and
      struggles in meeting, and collaborating to meet, care needs of adults with
      disabilities and/or mental health issues. Each focus group session was digitally
      recorded and transcribed; field notes were also taken and we thematically
      analysed data according to family versus agency perspectives of their successes
      and barriers in care provision and care collaboration. We found that family
      members desire greater and more effective support in enriching the lives of
      adults with disabilities and/or mental health issues and in preparing for age
      related changes. Agency representatives are keenly aware of the needs and
      challenges faced by families, yet grapple with being effective collaborators with
      families of widely varying priorities and styles of care and collaboration. 

PMID- 24118310
TI  - Efficacy of different solvents in removing gutta-percha from curved root canals:
      a micro-computed tomography study.
AB  - The aim of this study was to compare the root filling material that remained
      after retreatment of curved root canals with chloroform and Endosolv R as
      solvents. The evaluation employed micro-computed tomography (CT) imaging. Thirty
      six extracted molar teeth with curved roots were selected. After preparation with
      ProTaper rotary instruments, the canals were filled with gutta-percha and AH26
      sealer. The teeth were randomly divided into three groups according to solvent
      used (n = 12) as follows: group 1: chloroform; group 2: Endosolv R; group 3: no
      solvent (negative control). ProTaper Universal Retreatment files were used to
      remove each root canal filling and then the self-adjusting file was applied for
      two minutes. Preoperative and postoperative micro-CT images were used to assess
      the percentage of residual filling material. The mean percentage of residual
      filling material was quantified. There were no statistically significant
      differences between the groups in terms of percentage volume of residual root
      canal filling. 

PMID- 24118311
TI  - A multicenter study of shock pathways for subcutaneous implantable
      defibrillators.
AB  - INTRODUCTION: A purely subcutaneous implantable cardioverter defibrillator (ICD)
      requires higher energy but may be an effective alternative to transvenous ICDs to
      deliver lifesaving therapies. OBJECTIVE: To identify combinations of
      anteroposterior subcutaneous shock pathways and waveforms with defibrillation
      efficacy comparable to transvenous ICDs. METHODS: Defibrillation testing was
      performed in 141 patients temporarily implanted with an active can emulator and
      subcutaneous coil electrodes. The patients were subdivided into 5 groups within 2
      study phases. In all groups, a posterior electrode was positioned with its tip
      close to the spine. In the first study phase, 2 different can locations were
      evaluated: (1) an inframammary pocket (IM-1-750), or (2) a conventional
      infraclavicular pocket (IC-1-750). In both cases, a 70 J biphasic shock was used
      (peak voltage 750 V; 270 MUF capacitance). In the second phase, configuration IC
      1-750 was enhanced by the addition of a second (parasternal) subcutaneous
      electrode (IC-2-750). Furthermore, the effects of a different 70 J shock waveform
      (1,000 V, 160 MUF) were evaluated for configurations IM-1-750 and IC-2-750
      (becoming IM-1-1000 and IC-2-1000). RESULTS: The proportion of patients
      satisfying a defibrillation safety margin test of 2 consecutive successes at <=50
      J was 74%, 11%, and 44%, respectively, for the IM-1-750, IC-1-750, and IC-2-750
      configurations, and 93% and 86% for the IM-1-1000 and IC-2-1000 configurations.
      CONCLUSIONS: Defibrillation efficacy comparable to that of a transvenous system
      was achieved with an anteroposterior subcutaneous ICD configuration, with 160 MUF
      capacitance, 1,000 V, and 70 J output. An infraclavicular pocket location becomes
      feasible if a parasternal subcutaneous coil is added.

PMID- 24118312
TI  - Prevalence of oral white lesions due to qat chewing among women in Yemen.
AB  - OBJECTIVES: To investigate oral mucosal white lesions due to qat chewing among
      Yemeni women and their possible confounders (tobacco, water-pipe). PATIENTS AND
      METHODS: In a cross-sectional hospital study, 162 healthy women were divided into
      109 qat chewers and 53 non-qat chewers. Inclusion criteria were as follows: >=20
      years of age, chewing qat habitually >=5 years on one side. Women were
      interviewed about tobacco/water-pipe use and examined for oral mucosal lesions.
      RESULTS: Among chewers, white lesions were recorded in 82/109 (75.2%) at the
      chewing site. Lesions on the opposite side were recorded among 6/109 (5.5%) and
      among 7/53 (13.2%) non-chewers. Lesions reported among chewers were correlated
      with the side of chewing and with longer duration of the habit. The difference in
      the prevalence of white lesions present between cases and controls was
      significant (P < 0.000). When white lesions were correlated with the durations of
      chewing and water-pipe and cigarette smoking, results in terms of chewing were
      highly significant (P = 0.000) and those in terms of water-pipe smoking and
      cigarette smoking were not significant. CONCLUSION: Habitual chewing of qat
      fibres by Yemeni women over decades caused mucosal white lesions recorded on the
      chewing side irrespective of additional noxae as tobacco and water-pipe smoking.

PMID- 24118313
TI  - Age and sex differences in the incidence of esophageal adenocarcinoma: results
      from the Surveillance, Epidemiology, and End Results (SEER) Registry (1973-2008).
AB  - Risk factors driving sex disparity in esophageal cancer are unclear. Recent
      molecular evidence suggests hormonal factors. We conducted a national descriptive
      epidemiological study to assess the hypothesis that estrogen exposure could
      explain the male predominance in observed esophageal adenocarcinoma incidence. We
      analyzed the esophageal cancer incidence trends by histology and sex from 1973 to
      2008 in nine population-based cancer registries of the Surveillance,
      Epidemiology, and End Results (SEER) 9 Registry Database. We used age as a proxy
      for estrogen exposure in females. The collective age groups annual percentage
      change in esophageal adenocarcinoma for females is positive (0.03%; 95%
      confidence interval: 0.02, 0.03%) during the study period. Interestingly, the
      esophageal adenocarcinoma annual percentage change in incidence rates for females
      during the same time period is significantly negative from ages 50-54 to ages 60
      64. Even though the incidence of esophageal adenocarcinoma rises in both males
      and females, the male-to-female ratio across age peaks in the 50-54 years then
      decreases. Furthermore, the esophageal adenocarcinoma age-adjusted incidence rate
      in postmenopausal females age 80 and above increases with age unlike their male
      counterparts. Taken together, these data support the hypothesis that the
      endocrine milieu in pre- and perimenopausal females serves as a protective factor
      against esophageal adenocarcinoma, and with loss of estrogen or because of the
      increasing time period away from estrogen exposure, the rate of esophageal
      adenocarcinoma incidence increases in the older postmenopausal female. Because
      females comprise the largest portion of the elderly population with esophageal
      adenocarcinoma, these findings are significant. 

PMID- 24118314
TI  - No evidence for active human papillomavirus (HPV) in fields surrounding HPV
      positive oropharyngeal tumors.
AB  - BACKGROUND: Patients with human papillomavirus (HPV)-positive oropharyngeal
      squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV
      negative OPSCCs. Important factors contributing to this better prognosis are
      relatively low numbers of local/regional recurrences (LRRs) and second primary
      tumors (SPTs) in patients with HPV-positive OPSCC. These low numbers may be
      explained in addition by the absence of a 'field cancerization' effect, which is
      a cause of LRRs and SPTs in patients with HPV-negative OPSCC. We aimed to detect
      a possible 'field effect' in patients with HPV-positive OPSCC. As HPV is involved
      in the early stage of carcinogenesis in OPSCCs, its presence is considered a
      reliable marker for the detection of such a field effect. Therefore, the presence
      of transcriptionally active HPV was analyzed in the mucosa surrounding HPV
      positive OPSCCs. METHODS: We included 20 patients who were surgically treated for
      an HPV-positive OPSCC in the period 2000-2006. Of each patient, the formalin
      fixed paraffin-embedded tumor sample and all available resection margins were
      collected. In total, 97 resection margins were investigated with an average of
      five resection margins per tumor. All samples were analyzed for the presence of
      tumor and the presence of transcriptionally active HPV by HPV16-E6-mRNA
      detection. RESULTS: All tumors were HPV16-E6-mRNA positive. HPV16-E6-mRNA could
      be detected in the resection margins that contained tumor (n = 6). All tumor
      negative resection margins (n = 91) scored negative for HPV16-E6-mRNA.
      CONCLUSIONS: In conclusion, transcriptional active HPV could not be detected in
      the mucosa surrounding an HPV-positive OPSCC, which suggests the absence of field
      effect. This observation may explain the lower number of LRRs and SPTs in HPV
      positive patients.

PMID- 24118315
TI  - Gene expression patterns associated with caste and reproductive status in ants:
      worker-specific genes are more derived than queen-specific ones.
AB  - Variation in gene expression leads to phenotypic diversity and plays a central
      role in caste differentiation of eusocial insect species. In social Hymenoptera,
      females with the same genetic background can develop into queens or workers,
      which are characterized by divergent morphologies, behaviours and lifespan.
      Moreover, many social insects exhibit behaviourally distinct worker castes, such
      as brood-tenders and foragers. Researchers have just started to explore which
      genes are differentially expressed to achieve this remarkable phenotypic
      plasticity. Although the queen is normally the only reproductive individual in
      the nest, following her removal, young brood-tending workers often develop
      ovaries and start to reproduce. Here, we make use of this ability in the ant
      Temnothorax longispinosus and compare gene expression patterns in the queens and
      three worker castes along a reproductive gradient. We found the largest
      expression differences between the queen and the worker castes (~2500 genes) and
      the smallest differences between infertile brood-tenders and foragers (~300
      genes). The expression profile of fertile workers is more worker-like, but to a
      certain extent intermediate between the queen and the infertile worker castes. In
      contrast to the queen, a high number of differentially expressed genes in the
      worker castes are of unknown function, pointing to the derived status of
      hymenopteran workers within insects. 

PMID- 24118316
TI  - Evaluation of 2 trilostane protocols for the treatment of canine pituitary
      dependent hyperadrenocorticism: twice daily versus once daily.
AB  - BACKGROUND: Trilostane is the drug of choice to treat pituitary-dependent
      hyperadrenocorticism (PDH) in dogs, but there is still controversy about which
      protocol best controls the clinical signs and results of adrenal functioning
      test. OBJECTIVES: To compare the efficacy of twice daily (BID) versus once daily
      (SID) trilostane administration and to compare the safety of both protocols in
      the treatment of dogs with PDH. ANIMALS: Thirty-two client-owned dogs diagnosed
      with PDH between 2008 and 2010 and treated with trilostane either BID or SID.
      METHODS: In this prospective randomized study, 2 trilostane protocols were
      evaluated on the basis of the owner's perception of clinical signs, on the
      results of laboratory tests, and on the results of the ACTH stimulation test in
      dogs with PDH. Dogs were followed up for a period of 1 year. RESULTS: During the
      study, more dogs in the BID group had complete clinical recovery than in the SID
      group. However, there was no significant difference in the mean post-ACTH
      cortisol concentration between groups. Basal cortisol concentration at 6 months
      was higher in animals treated SID compared with animals treated BID. Mean total
      daily doses of trilostane used to control PDH, as well as adverse effects
      observed in the course of the study, in both groups were not statistically
      different. CONCLUSION AND CLINICAL IMPORTANCE: Adverse effects were mild using
      either protocol of treatment. Using trilostane BID might increase the number of
      dogs with a good clinical response compared with using trilostane SID.

PMID- 24118317
TI  - An 'ice age' concept? The use of ice in the treatment of acute haemarthrosis in
      haemophilia.

PMID- 24118318
TI  - Early molecular assessment of osseointegration in humans.
AB  - OBJECTIVE: To determine the early temporal-wide genome transcription regulation
      by the surface topography at the bone-implant interface of implants bearing
      microroughened or superimposed nanosurface topology. MATERIALS AND METHODS: Four
      commercially pure titanium implants (2.2 * 5.0 mm) with either a moderately
      roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed)
      were placed (n = 2/surface) in edentulous sites of eleven systemically healthy
      subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from
      cells adherent to retrieved implants. A whole-genome microarray using the
      Affymetrix Human gene 1.1 ST Array was used to describe the gene expression
      profiles that were differentially regulated by the implant surfaces. RESULTS:
      There were no significant differences when comparing the two implant surfaces at
      each time point. However, the microarray identified several genes that were
      differentially regulated at day 7 vs. day 3 for both implant surfaces.
      Functionally relevant categories related to the extracellular matrix (ECM),
      collagen fibril organization, and angiogenesis were upregulated at both surfaces
      (day7 vs. day3). Abundant upregulation of several differential markers of
      alternative activated macrophages was observed (e.g., MRC1, MSR1, MS4A4A,
      SLC38A6, and CCL18). The biological processes involved with the
      inflammatory/immune response gene expression were concomitantly downregulated.
      CONCLUSIONS: Gene regulation implicating collagen fibrillogenesis and ECM
      organization as well as the inflammatory/immune responses involving the
      alternative activated pathway are observed in implant adherent cells at early (3
      7 days) after implantation. These gene expression events may indicate a pivotal
      role of collagen fibrillogenesis as well as immunomodulation in altering bone
      accrual and biomechanical physical properties of the implant-bone interface.

PMID- 24118319
TI  - Correlation between the TISS-28 and NEMS indicators in an intensive care unit.
AB  - Cross-sectional study aimed to analyse and compare the correlation between the
      Therapeutic Intervention Scoring System (TISS)-28 and Nine Equivalents of Nursing
      Manpower Use (NEMS) indicators with a sample of 725 patients, for which data was
      collected from the computerized system of a university hospital. The findings of
      the present study well demonstrated a strong correlation between the TISS-28 and
      NEMS, both at the time of patient admission and discharge (0.888 and 0.885; P <
      0.001), although there is a dispersion of 21% in the data and established cut-off
      points to discriminate with greater power the death and no death scenarios.
      Further research is still necessary to confirm the possibility of replacing the
      TISS-28 scoring instrument with NEMS.

PMID- 24118320
TI  - Constraints on the evolution of function-valued traits: a study of growth in
      Tribolium castaneum.
AB  - Growth trajectories often impact individual fitness. They are continuous by
      nature and so are amenable to analysis using a function-valued (FV) trait
      framework to reveal their underlying genetic architecture. Previous studies have
      found high levels of standing additive genetic (co)variance for growth
      trajectories despite the expectation that growth should be responding to frequent
      strong directional selection. In this study, the FV framework is used to estimate
      the additive genetic covariance function for growth trajectories in larval
      Tribolium castaneum to address questions about standing additive genetic
      (co)variance and possible evolutionary constraints on growth and to predict
      responses to four plausible selection regimes. Results show that additive genetic
      (co)variance is high at the early ages, but decreases towards later ages in the
      larval period. A selection gradient function of the same size and in the same
      direction of the first eigenfunction of the G-function should give the maximal
      response. However, evolutionary constraints may be acting to keep this maximal
      response from being realized, through either conflicting effects on survivability
      and fecundity of larger body size, few evolutionary directions having sufficient
      additive variance for a response, genetic trade-offs with other traits or
      physiological regulatory mechanisms. More light may be shed on these constraints
      through the development of more sophisticated statistical approaches and
      implementation of additional empirical studies to explicitly test for specific
      types of constraints. 

PMID- 24118321
TI  - B3GNT3 expression suppresses cell migration and invasion and predicts favorable
      outcomes in neuroblastoma.
AB  - Aberrant expression of the simple mucin-type carbohydrate antigens such as T, Tn,
      sialyl-T and sialyl-Tn is associated with poor prognosis in several cancers.
      beta1,3-N-acetylglucosaminyltransferase-3 (B3GNT3), a member of the beta3GlcNAcT
      family, is responsible for forming extended core 1 (T antigen) oligosaccharides.
      The role of B3GNT3, which is expressed in various tissues including human fetal
      brain, in regulating neuroblastoma (NB) formation and cell behaviors remains
      unclear. Here, we showed that increased B3GNT3 expression evaluated using
      immunohistochemistry in NB tumor tissues correlated well with the histological
      grade of differentiation as well as a favorable Shimada's subset of pathology.
      Univariate and multivariate analyses revealed that positive B3GNT3 expression in
      tumor tissues predicted a favorable prognosis in NB patients independent of other
      prognostic markers. B3GNT3 overexpression suppresses T antigen formation and
      malignant phenotypes including migration and invasion of SK-N-SH cells, whereas
      B3GNT3 knockdown enhances these phenotypes of SK-N-SH cells. Moreover, B3GNT3
      expression decreased phosphorylation of focal adhesion kinase (FAK), Src,
      paxillin, Akt and ERK1/2. We conclude that B3GNT3 predicts a favorable cancer
      behavior of NB and suppresses malignant phenotypes by modulating mucin-type O
      glycosylation and signaling in NB cells. 

PMID- 24118322
TI  - Improvement in the outcome of invasive fusariosis in the last decade.
AB  - Invasive fusariosis (IF) has been associated with a poor prognosis. Although
      recent series have reported improved outcomes, the definition of optimal
      treatments remains controversial. The objective of this study was to evaluate
      changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11
      countries, comparing demographics, clinical findings, treatment and outcome in
      two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%)
      had haematological disease. Primary treatment with deoxycholate amphotericin B
      was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32%
      vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more
      frequent in period 2. The 90-day probabilities of survival in periods 1 and 2
      were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities
      of survival were 60% with voriconazole, 53% with a lipid formulation of
      amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables
      associated with poor prognosis (death 90 days after the diagnosis of fusariosis)
      by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR)
      2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI
      1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI
      1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with
      an increased use of voriconazole and combination therapies. There has been a 21%
      increase in survival rate in the last decade.

PMID- 24118323
TI  - Development of a quantitative food frequency questionnaire for use among rural
      South Africans in KwaZulu-Natal.
AB  - BACKGROUND: South Africa is experiencing a dietary and lifestyle transition as
      well as increased rates of noncommunicable chronic diseases. Limited information
      is available on the diets of rural populations. The present study aimed to
      characterise the diets of men and women from rural KwaZulu-Natal (KZN) and
      develop a quantitative food-frequency questionnaire (QFFQ) specific for this
      population. METHODS: A cross-sectional study was carried out by collecting single
      24-h dietary recalls from 81 adults and developing a QFFQ in Empangeni, KZN,
      South Africa. RESULTS: The diet of this population was limited in variety, high
      in plant-based foods (especially cereals and beans), and low in animal products,
      vegetables and fruits. Amaize meal staple (Phutu) was consumed by over 80% of
      subjects and accounted for almost 45% of energy intake, as well as making an
      important contribution to fat and protein intake. Most of the protein consumed by
      the study population was plant-based protein, with almost 40% being obtained from
      the consumption of phutu and beans. A culturally appropriate QFFQ was developed
      that includes 71 food and drink items, of which 16 are composite dishes unique to
      this population. CONCLUSIONS: Once validated, this QFFQ can be used to monitor
      diet-disease associations, evaluate nutritional interventions and investigate
      dietary changes in this population.

PMID- 24118324
TI  - Paradoxical effect of gonadotrophin-inhibiting hormone to negatively regulate
      neuropeptide Y neurones in mouse arcuate nucleus.
AB  - Regulation of reproduction and energy homeostasis are linked, although our
      understanding of the central neural mechanisms subserving this connection is
      incomplete. Gonadotrophin-inhibiting hormone (GnIH) is a neuropeptide that
      negatively regulates reproduction and stimulates food intake. Neuropeptide Y
      (NPY) and products of the pro-opiomelanocortin (POMC) precursor (beta-endorphin
      melanocortins) are appetite regulating peptides produced in the neurones of the
      arcuate nucleus; these peptides also regulate reproduction. In the present study,
      we determined the effects of GnIH on NPY and POMC neurones. Using brain slices
      from mice with transgenes for fluorescent tags in the two types of neurone and
      patch clamp electrophysiology, a predominant inhibitory effect of GnIH was
      observed. GnIH (100 nM) inhibited the firing rate in POMC cells, confirming the
      results of previous studies and consistent with the stimulatory effect of GnIH on
      food intake. Paradoxically (i.e. because both GnIH and NPY stimulate food
      intake), GnIH also had a predominantly inhibitory effect on action potential
      activity in NPY cells. GnIH also inhibited the secretion of NPY and alpha
      melanocyte-stimulating hormone secretion in incubated hypothalamic blocks. GnIH
      (100 ng) injected into the cerebral ventricles of mice did not increase the
      number of NPY cells that were positively immunostained for c-Fos. Finally, dual
      label immunocytochemistry showed that 20% of NPY neurones had close contacts from
      GnIH fibres/varicosities. In conclusion, we confirm a negative effect of GnIH on
      POMC cells and demonstrate a paradoxical reduction of electrophysiological and
      functional activity in NPY cells.

PMID- 24118325
TI  - Stem cells in the skin and their role in oncogenesis.
AB  - Stem cells generate great interest because they hold the promise for treatment of
      various incurable diseases. Several distinct stem cell populations have been
      identified in each organ, including the skin. As the skin is the largest organ in
      the body and is easily accessible, cutaneous stem cells have raised significant
      hopes for being a rich source of easily available multipotent stem cells. Genetic
      alterations and mutations in stem cells are being proposed as initiation step in
      multiple cancers. Small populations of oncogenic stem cells termed as cancer stem
      cells or tumour-initiating cells have been identified in multiple tumours,
      including squamous cell carcinomas, and melanomas that can sustain tumour growth,
      underlie its malignant behaviour and initiate distant metastases. These cells are
      controlled and regulated by the same pathways that are also responsible for
      maintenance and differentiation of normal stem cells. Developing a targeted
      therapy against the oncogenic stem cells and dysregulated members of the
      signalling pathways may be the key to understanding and treating skin cancers
      like melanomas, for which we still do not have an effective treatment. 

PMID- 24118326
TI  - Children of Parents With Chronic Noncancer Pain: A Comprehensive Review of the
      Literature.
AB  - TOPIC: Chronic noncancer pain (CNCP) is a prevalent occurrence and is experienced
      by adults in their child-rearing years. Somatic or psychiatric illness in a
      parent constitutes a potential threat to the physical, mental health, and
      normative development in children. PURPOSE: A comprehensive review of the
      literature was performed to answer the question: What are the effects of parental
      CNCP on children in the family system? SOURCES USED: The search was performed
      using the Cumulative Index to Nursing and Allied Health Literature, Medline,
      PsycINFO, and Academic Search Premier. Search terms used were "parent pain or
      parent chronic pain or parent illness or parent chronic illness" and "child or
      adolescent or teenager." Inclusion and exclusion criteria were developed a
      priori. Eighteen articles (n = 18) met criteria and were included in the sample.
      CONCLUSIONS: Three clusters were identified: (a) child/adolescent somatic
      complaints or behavior; (b) child/adolescent internalizing or externalizing
      symptoms; and (c) important mediating and moderating variables. The results of
      this review show that children and adolescents whose parents suffer from CNCP are
      at risk for more and similar-to-parent pain complaints and greater degree of
      internalizing and externalizing symptoms than those with healthy parents.
      Implications for clinical nursing practice and research are given.

PMID- 24118327
TI  - Volume matters: CT-based renal cortex volume measurement in the evaluation of
      living kidney donors.
AB  - Currently, no international standard for the pre-transplant evaluation of living
      donor renal function exists. Following a standardized questionnaire on current
      practice in all Eurotransplant (ET) centers, we compared a new CT-based technique
      to measure renal cortex volume with our standard of DTPA-clearance combined with
      MAG3-scintigraphy (DTPA * MAG3) and with creatinine-based methods in 167
      consecutive living kidney donors. Most ET centers use creatinine-clearance (64%)
      to measure total renal function and radioistopic methods (82%) to assess split
      renal function. Before transplantation, CT-measured total cortex volume (r =
      0.67; P < 0.001) and estimated GFR using the Cockcroft-Gault formula [eGFR(CG)]
      (r = 0.55; P < 0.001) showed the strongest correlation with DTPA-clearance. In
      contrast, the correlation between DTPA-clearance and creatinine clearance was
      weak (r = 0.21; P = 0.02). A strong correlation was observed between CT-measured
      split cortex volume and MAG3-measured split renal function (r = 0.93; P < 0.001).
      A strong correlation was also found between pre-transplant split renal function
      assessed by eGFR(CG) together with cortex volume measurement and post-transplant
      eGFR(CG) of both, the donor (r = 0.83; P < 0.001) and the recipient (r = 0.75; P
      < 0.001). In conclusion CT-based assessment of renal cortex volume bears the
      potential to substitute existing methods to assess pre-transplant living donor
      split renal function.

PMID- 24118328
TI  - An investigation into the relevance of action planning, theory of planned
      behaviour concepts, and automaticity for fruit intake action control.
AB  - OBJECTIVES: In the action control framework, intention-behaviour discordance is
      studied around public health guidelines. Although this framework has been applied
      to physical activity behaviours, it has only seen very limited attention
      regarding fruit intake. The purpose of this study was therefore to investigate
      distributions and predictors of fruit intake intention-behaviour discordance.
      DESIGN: Prospective correlational design. METHODS: Data were obtained from
      undergraduate students (n = 413) using validated questionnaires. Variables from
      the theory of planned behaviour, automaticity, and action planning were assessed
      at baseline, and fruit intake was assessed 2 weeks later. Data were analysed
      using discriminant function analyses and analyses of variance. RESULTS: The
      proportion of unsuccessful intenders ranged from 39.2% to 80.8%. There was a
      larger proportion of fruit intake intenders amongst those who reported strong
      automatic fruit intake. Action control was predicted by fruit intake automaticity
      and affective attitudes, but the strongest predictor was perceived behavioural
      control. No action planning items were related to fruit intake action control.
      CONCLUSIONS: There is considerable asymmetry in the intention-fruit intake
      relationship. An application of the action control framework may stimulate debate
      on the applicability of intention-based models at the public health level.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Intention is
      theorized to be a key construct in fruit intake. Studies in the physical activity
      domain indicate that nearly half of the people with positive intentions fail to
      subsequently act. What does this study add? The proportion of unsuccessful
      intenders ranged from 39.2% to 80.8%. Holding positive intentions is not
      sufficient to consume fruit at suggested public health guidelines. Perceived
      behavioural control is the most important predictor of fruit intake action
      control.

PMID- 24118329
TI  - Post-transplant lymphoproliferative disorder after pancreas transplantation: a
      United Network for Organ Sharing database analysis.
AB  - There are not a great deal of data on post-transplant lymphoproliferative
      disorder (PTLD) following pancreas transplantation. We analyzed the United
      Network for Organ Sharing national database of pancreas transplants to identify
      predictors of PTLD development. A univariate Cox model was generated for each
      potential predictor, and those at least marginally associated (p < 0.15) with
      PTLD were entered into a multivariable Cox model. PTLD developed in 43 patients
      (1.0%) of 4205 pancreas transplants. Mean follow-up time was 4.9 +/- 2.2 yr. In
      the multivariable Cox model, recipient EBV seronegativity (HR 5.52, 95% CI: 2.99
      10.19, p < 0.001), not having tacrolimus in the immunosuppressive regimen (HR
      6.02, 95% CI: 2.74-13.19, p < 0.001), recipient age (HR 0.96, 95% CI: 0.92-0.99,
      p = 0.02), non-white ethnicity (HR 0.11, 95% CI: 0.02-0.84, p = 0.03), and HLA
      mismatching (HR 0.80, 95% CI: 0.67-0.97, p = 0.02) were significantly associated
      with the development of PTLD. Patient survival was significantly decreased in
      patients with PTLD, with a one-, three-, and five-yr survival of 91%, 76%, and
      70%, compared with 97%, 93%, and 88% in patients without PTLD (p < 0.001). PTLD
      is an uncommon but potentially lethal complication following pancreas
      transplantation. Patients with the risk factors identified should be monitored
      closely for the development of PTLD.

PMID- 24118330
TI  - Predictive factors for failure of salpingostomy in ectopic pregnancy.
AB  - AIM: The objective of this study was to review our experience with ectopic
      pregnancy management and to evaluate major predictive factors for failure of
      conservative linear salpingostomy. METHODS: Seven hundred and ninety-seven cases
      that were treated for ectopic pregnancy in our clinic between October 2005 and
      September 2011 were analyzed retrospectively for incidence and treatment options.
      We defined failure as rising or plateauing postoperative serum beta-hCG levels
      that required additional medical or surgical treatment after initial removal of
      the ectopic pregnancy by laparoscopy or by laparotomy. We examined the risk
      factors consisting of preoperative beta-hCG, size and location of ectopic
      lesions, the presence of fetal heart beat and tubal condition that can influence
      the failure or success of conservative salpingostomy. RESULTS: In total, 403
      patients were treated conservatively. These conservative managements consist of
      334 salpingostomies performed by laparoscopy and 69 by laparotomy. Because of
      persistent ectopic pregnancy, 16 patients underwent medical treatment. In total,
      387 patients were treated successfully with conservative management and 16
      patients were treated unsuccessfully with conservative management. When variables
      of P < 0.05 were subjected to multivariate analysis, size of the ectopic
      pregnancy of 33.5 mm or greater and fimbrial and isthmic region ectopic
      pregnancies were significantly associated with the failure rate. CONCLUSIONS: The
      size of the ectopic pregnancy and fimbrial and isthmic region ectopic pregnancies
      were determinant of failure of conservative surgery. Our success rate in the
      ruptured group is not an underestimated value to dissuade patients wishing to
      maintain fertility by undergoing salpingectomy. So, the conservative approach to
      ectopic pregnancy should be undertaken after careful patient evaluation.

PMID- 24118331
TI  - Genetic signatures of natural selection in response to air pollution in red
      spruce (Picea rubens, Pinaceae).
AB  - One of the most important drivers of local adaptation for forest trees is
      climate. Coupled to these patterns, however, are human-induced disturbances
      through habitat modification and pollution. The confounded effects of climate and
      disturbance have rarely been investigated with regard to selective pressure on
      forest trees. Here, we have developed and used a population genetic approach to
      search for signals of selection within a set of 36 candidate genes chosen for
      their putative effects on adaptation to climate and human-induced air pollution
      within five populations of red spruce (Picea rubens Sarg.), distributed across
      its natural range and air pollution gradient in eastern North America.
      Specifically, we used FST outlier and environmental correlation analyses to
      highlight a set of seven single nucleotide polymorphisms (SNPs) that were overly
      correlated with climate and levels of sulphate pollution after correcting for the
      confounding effects of population history. Use of three age cohorts within each
      population allowed the effects of climate and pollution to be separated
      temporally, as climate-related SNPs (n = 7) showed the strongest signals in the
      oldest cohort, while pollution-related SNPs (n = 3) showed the strongest signals
      in the youngest cohorts. These results highlight the usefulness of population
      genetic scans for the identification of putatively nonneutral evolution within
      genomes of nonmodel forest tree species, but also highlight the need for the
      development and application of robust methodologies to deal with the inherent
      multivariate nature of the genetic and ecological data used in these types of
      analyses. 

PMID- 24118332
TI  - Complementary medicine use among cancer patients receiving radiotherapy and
      chemotherapy: methods, sources of information and the need for counselling.
AB  - Complementary medicine (CM) use is common among cancer patients. However, little
      is known about CM products that are utilised during radiotherapy and/or
      chemotherapy. Out of 62 cancer patients who completed a specialised survey, 35
      (56%) consumed some type of CM during active anti-cancer therapy. Cancer patients
      reported the use of herbal teas (52%), vitamins and other dietary supplements
      (45%), vegetables and juices (39%), special diets (19%), herbal medicines,
      including Chinese medicines (19%) and 'immunomodulators' (3%). Most of patients
      (86%) consumed CM products every day. However, nearly 47% of CM users did not
      admit this to their oncologists. Majority of CM users (85%) were convinced that
      supplementary products increase the efficacy of standard anti-cancer therapy and
      prolong their survival. Information about CM was mainly obtained through internet
      sources (36%), books and brochures (25%). Although most CM users (82%) trusted
      the received information, 73% of them admitted that additional information about
      CM methods would be necessary. Patients would like to receive additional
      information through a specialised consultation (60%), but also from brochures
      (44%) and the internet (20%). Adequate counselling of patients is of paramount
      importance since some CM methods may cause significant side effects and decrease
      the efficacy of radiotherapy and/or chemotherapy. 

PMID- 24118333
TI  - Cutting edge: IL-10-producing regulatory B cells in early human pregnancy.
AB  - PROBLEM: The function of IL-10 producing regulatory B cells (Breg) during
      gestation is unknown. Here, we aimed to understand their participation in early
      pregnancy. METHOD: CD19(+) CD24(hi) CD27(+) B cell frequency, measured by flow
      cytometry, increased with pregnancy onset but not in the case of spontaneous
      abortions. RESULTS: B cells from non-pregnant women cultured with serum from
      normal pregnant women produced higher IL-10 levels than those cultured with serum
      from spontaneous abortion patients or autologous serum. CD19(+) -activated B
      cells from pregnant women strongly suppressed TNF-a production by CD4(+) T cells
      when cocultured. We identified hCG as an important factor regulating the number
      and function of Breg during pregnancy. CONCLUSIONS: Breg emerge as important
      players in pregnancy; they suppress undesired immune responses from maternal T
      cells and are therefore important for tolerance acquisition.

PMID- 24118334
TI  - Effect of ferrule height and glass fibre post length on fracture resistance and
      failure mode of endodontically treated teeth.
AB  - The purpose of this study was to evaluate the combined effect of ferrule height
      and post length on fracture resistance and failure mode of endodontically treated
      teeth restored with glass fibre posts, composite resin cores and crowns. Ninety
      human maxillary central incisors were endodontically treated and divided into
      three groups (n = 30) according to the ferrule heights: 4, 2 and 0 mm,
      respectively. Post spaces in each group were prepared at 2/3, 1/2 and 1/3 of the
      root length (n = 10). The specimens were received fibre posts, composite resin
      core build up and cast metal crowns. After thermocycling, compressive static load
      was applied at an angle of 135 degrees  to the crowns. Two-way analysis of
      variance showed significant differences in the failure load in the ferrule height
      groups, no significant differences in post length groups and no significant
      interaction between ferrule heights and post lengths. More restorable failure
      modes were observed. 

PMID- 24118335
TI  - Refractory thrombotic thrombocytopenic purpura in a 16-year-old girl: successful
      treatment with bortezomib.
AB  - We present a case of a 16-year-old girl with autoimmune thrombotic
      thrombocytopenic purpura (TTP), refractory to plasma exchange and high-dose
      prednisone. Despite the additional treatment with rituximab, she developed renal
      and neurological complications with ongoing hemolysis and thrombocytopenia.
      Bortezomib, a proteasome inhibitor and thereby blocking plasma cells, was added,
      and our patient recovered. We suggest that bortezomib can be of additional value
      in severe immunologically mediated TTP in adolescents. Its use may prevent the
      necessity of other invasive therapies, such as splenectomy, with significant side
      effects. 

PMID- 24118336
TI  - Successful ablation of iatrogenic intraoral hypertrichosis post mandibular
      reconstruction using a thermolysis hair epilation technique.

PMID- 24118337
TI  - Antimicrobial peptides and pro-inflammatory cytokines are differentially
      regulated across epidermal layers following bacterial stimuli.
AB  - The skin is a natural barrier between the body and the environment and is
      colonised by a large number of microorganisms. Here, we report a complete
      analysis of the response of human skin explants to microbial stimuli. Using this
      ex vivo model, we analysed at both the gene and protein level the response of
      epidermal cells to Staphylococcus epidermidis (S. epidermidis) and Pseudomonas
      fluorescens (P. fluorescens), which are present in the cutaneous microbiota. We
      showed that both bacterial species affect the structure of skin explants without
      penetrating the living epidermis. We showed by real-time quantitative polymerase
      chain reaction (qPCR) that S. epidermidis and P. fluorescens increased the levels
      of transcripts that encode antimicrobial peptides (AMPs), including human beta
      defensin (hBD)2 and hBD3, and the pro-inflammatory cytokines interleukin (IL)
      1alpha and (IL)-1-beta, as well as IL-6. In addition, we analysed the effects of
      bacterial stimuli on the expression profiles of genes related to innate immunity
      and the inflammatory response across the epidermal layers, using laser capture
      microdissection (LCM) coupled to qPCR. We showed that AMP transcripts were
      principally upregulated in suprabasal keratinocytes. Conversely, the expression
      of pro-inflammatory cytokines was upregulated in the lower epidermis. These
      findings were confirmed by protein localisation using specific antibodies coupled
      to optical or electron microscopy. This work underscores the potential value of
      further studies that use LCM on human skin explants model to study the roles and
      effects of the epidermal microbiota on human skin physiology.

PMID- 24118338
TI  - Ancient trade routes shaped the genetic structure of horses in eastern Eurasia.
AB  - Animal exchange networks have been shown to play an important role in determining
      gene flow among domestic animal populations. The Silk Road is one of the oldest
      continuous exchange networks in human history, yet its effectiveness in
      facilitating animal exchange across large geographical distances and
      topographically challenging landscapes has never been explicitly studied. Horses
      are known to have been traded along the Silk Roads; however, extensive movement
      of horses in connection with other human activities may have obscured the genetic
      signature of the Silk Roads. To investigate the role of the Silk Roads in shaping
      the genetic structure of horses in eastern Eurasia, we analysed microsatellite
      genotyping data from 455 village horses sampled from 17 locations. Using least
      cost path methods, we compared the performance of models containing the Silk
      Roads as corridors for gene flow with models containing single landscape
      features. We also determined whether the recent isolation of former Soviet Union
      countries from the rest of Eurasia has affected the genetic structure of our
      samples. The overall level of genetic differentiation was low, consistent with
      historically high levels of gene flow across the study region. The spatial
      genetic structure was characterized by a significant, albeit weak, pattern of
      isolation by distance across the continent with no evidence for the presence of
      distinct genetic clusters. Incorporating landscape features considerably improved
      the fit of the data; however, when we controlled for geographical distance, only
      the correlation between genetic differentiation and the Silk Roads remained
      significant, supporting the effectiveness of this ancient trade network in
      facilitating gene flow across large geographical distances in a topographically
      complex landscape. 

PMID- 24118339
TI  - Treatment of esophageal perforation in octogenarians: a multicenter study.
AB  - Esophageal perforation is associated with significant mortality, and this may
      markedly increase with advanced age. This multicenter study investigates this
      issue in patients older than 80 years. Data on 33 patients >80 years old who
      underwent conservative (10 patients), endoclip (one patient), stent grafting (11
      patients), or surgical treatment (11 patients) for esophageal perforation were
      collected from nine centers. Surgical repair consisted of repair on drain in one
      patient, primary repair in seven patients, and esophagectomy in two patients.
      Among patients who underwent stent grafting, one required repeat stenting and
      another stent graft repositioning. One patient was converted to surgical repair
      after stent grafting. Thirteen patients (39.4%) died during the 30-day and/or in
      hospital stay. Their mortality was significantly higher than in a series of
      patients<80 years old (13.0%, 21/161 patients, P=0.001). Three patients (30.0%)
      died after conservative treatment, one (100%) after treatment with endoclips,
      five (45.5%) after stent grafting, and four (36.4%) after surgical repair
      (P=0.548). Early survival with salvaged esophagus was 42.4% (conservative
      treatment: 70.0% endoclips 0%, stent grafting: 54.5%, and surgical repair: 54.5%,
      respectively, P=0.558). Estimated glomerular filtration rate<60 mL/minute/1.73 m2
      (70.0% vs. 25.0%, P=0.043) and sepsis (100% vs. 32.1%, P=0.049) at presentation
      were associated with increased risk of early mortality in univariate analysis.
      Esophageal perforation in octogenarians is associated with very high early and
      intermediate high mortality irrespective of the treatment method used.

PMID- 24118340
TI  - Measurement equivalence of touch-screen computerized and paper-based diabetes
      specific quality-of-life questionnaires.
AB  - Current advances in technology have enabled the development of a computer-based
      questionnaire that provides advantages over the paper-based mode of
      administration, such as automatic data entry, storage and calculations. However,
      before implementing a computer-based questionnaire, its equivalence with the
      original paper-based questionnaire must first be demonstrated. The purpose of
      this study was to evaluate the measurement equivalence of the computerized
      Diabetes-Specific Quality-of-Life questionnaire (cD-QOL) with its original paper
      based counterpart. A two-period crossover design was used in this study. The
      measurement equivalence was evaluated using quadratic weighted kappa
      coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD
      QOL was equivalent to its original paper-based counterpart. Participants
      preferred the cD-QOL over the paper-based questionnaire and reported that it was
      easy to use. 

PMID- 24118341
TI  - Reciprocal effects of Interferon-gamma and IL-4 on differentiation to osteoclast
      like cells by RANKL or LPS.
AB  - OBJECTIVE: LPS can induce differentiation to osteoclast-like cells independent of
      RANKL. In comparison with RANKL, the effects of Th1 and Th2 cytokines on LPS
      induced osteoclastogenesis have not been extensively studied. In this study, we
      investigated the effects of IFN-gamma and IL-4 on RANKL- or LPS-induced
      osteoclastogenesis. MATERIALS AND METHODS: RAW 264.7 cells were induced to
      differentiate into osteoclast-like cells by RANKL or LPS, in the absence or
      presence of IFN-gamma or IL-4. The number of TRAP-positive, multinucleated (>= 3
      nuclei) cells (MNCs) was counted. mRNA and protein levels of TRAP and cathepsin K
      were determined by quantitative RT-PCR and Western immunoblot, respectively.
      Expression of other genes implicated in osteoclast and macrophage differentiation
      and inflammation was also quantitated and was subsequently assessed in bone
      marrow-derived macrophages (BMMs). Phagocytic capacity of differentiated RAW264.7
      was investigated by the uptake of pHrodo S. aureus bioparticles conjugates.
      RESULTS: In contrast to the RANKL-treated cell population that gained more
      macrophage-like properties at the level of gene and protein expression as well as
      phagocytosis in the presence of IFN-gamma or IL-4, the LPS-induced population
      gained more osteoclast-like properties by the addition of the same factors.
      CONCLUSION: These data suggest that the adaptive immune system, through either
      Th1 or Th2 cytokines, is able to modify the differentiation process of
      osteoclasts in inflammatory situations. Moreover, the study provides an example
      of different regulation of osteoclast differentiation during physiological and
      inflammatory conditions.

PMID- 24118342
TI  - Renal sympathetic denervation as an adjunct to catheter ablation for the
      treatment of ventricular electrical storm in the setting of acute myocardial
      infarction.

PMID- 24118343
TI  - A case in Europe of feline histoplasmosis apparently limited to the skin.
AB  - BACKGROUND: Histoplasma capsulatum has a worldwide distribution, but reports in
      Europe remain rare. We present the second report of histoplasmosis in a cat in
      Europe and, to the best of our knowledge, the first case of feline histoplasmosis
      infection apparently limited to the skin. CASE REPORT: A 6-year-old male
      castrated outdoor cat was presented to the dermatology service with a history of
      skin lesions evolving over 1 month and consisting of multiple papules and nodules
      on the head and neck. General examination was unremarkable. Cytological
      examination of the ulcerated nodules revealed a pyogranulomatous infiltrate, with
      numerous macrophages containing oval yeast-like cells, 2-5 MUm in size, with a
      central, lightly basophilic core surrounded by a clear halo. A tentative
      diagnosis of fungal infection was made, and skin biopsy specimens were taken.
      Histological examination confirmed the cytology findings, and Grocott staining
      showed numerous organisms suggestive of Histoplasma within macrophages. Thoracic
      radiographs, abdominal ultrasound and routine laboratory testing were
      unremarkable. Fungal culture of a nodule was negative. PCR of total DNA extracted
      from the infected tissue and subsequent sequencing confirmed the diagnosis of H.
      capsulatum var. capsulatum. Surgical excision of the other nodules was performed,
      and the cat was treated with oral itraconazole 5 mg/kg once daily; 12 weeks after
      initial consultation, no lesions were visible. No recurrence was observed during
      an 8 month follow-up period. CONCLUSIONS AND CLINICAL IMPORTANCE: Histoplasmosis
      should be included in the differential diagnosis of nodular diseases of cats
      worldwide.

PMID- 24118344
TI  - Factor XIII deficiency: complete phenotypic characterization of two cases with
      novel causative mutations.
AB  - Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A2B2) in the
      plasma and as dimer (FXIII-A2) in cells. Activated FXIII mechanically stabilizes
      fibrin and protects it from fibrinolysis by cross-linking fibrin chains and
      alpha2-plasmin inhibitor to fibrin. FXIII is essential to maintaining
      haemostasis, and its deficiency causes severe bleeding diathesis. Due to improper
      laboratory practices, FXIII deficiency is considered the most under-diagnosed
      bleeding disorder. The aim of this study was to demonstrate in two cases how
      FXIII deficiency is properly diagnosed and classified, and to compare results of
      laboratory analysis and clinical symptoms. FXIII activity from plasma and
      platelets was measured by a modified ammonia release assay, while FXIII-A2B2,
      FXIII-A and FXIII-B antigens were determined by ELISA. The exon-intron boundaries
      and the promoter region of F13A1 gene were amplified by PCR and the amplified
      products were analysed by direct fluorescent sequencing. FXIII-A mRNA in
      platelets was determined by RT-qPCR. Two children with severe bleeding symptoms
      were investigated. In both cases FXIII activity and FXIII-A antigen were
      undetectable in the plasma and platelet lysate. In the plasma no FXIII-A2B2
      antigen was found, while FXIII-B antigen was >30% in both cases. Proband1 was a
      compound heterozygote possessing a known missense mutation (c.980G>A,
      p.Arg326Gln) and a novel splice-site mutation (c.1112+2T>C). Proband2 was
      homozygote for a novel single nucleotide deletion (c.212delA) leading to early
      stop codon. The discovered mutations explain the severity of clinical symptoms
      and the laboratory data. Methods precise in the low activity/antigen range are
      required to draw valid conclusion on phenotype-genotype relationship.

PMID- 24118345
TI  - Crestal bone loss related to immediate implants in crestal and subcrestal
      position: a pilot study in dogs.
AB  - OBJECTIVES: The aim of the present study was to compare crestal bone loss with
      different implant designs inserted immediately in crestal or subcrestal position
      in post-extraction sockets in a dog model. MATERIALS AND METHODS: The mandibular
      second, third, fourth premolars, and the first molars of six adult fox hound dogs
      were extracted bilaterally, and 48 implants were placed immediately in both hemi
      arches of each dog. Randomly, eight implants (sky classic ((r)) and blue sky
      ((r)) ) were inserted, four crestally (control group) and four 2 mm subcrestally
      (test group). Both groups were treated with a minimal mucoperiosteal flap
      elevation approach. After a 12-week healing period, the animals were sacrificed,
      and samples were obtained. Biopsies were processed for ground sectioning.
      Histomorphometric analysis was carried out to compare buccal and lingual bone
      height loss. RESULTS: All implants were clinically and histologically
      osseointegrated. Healing patterns examined microscopically at eight and 12 weeks
      for both groups (crestal and subcrestal) yielded similar qualitative bone
      findings. At 12 weeks, the distance from the top of the implant collar to the
      first BIC (ISBc) showed significant difference between implant positions (crestal
      or subcrestal) in the buccal aspect (P = 0.1253), values for the crestal group
      being higher (1.79 +/- 0.3 mm) in comparison with the subcrestal group (0.89 +/-
      0.5 mm). Better results were achieved by both implant designs when implants were
      placed in the deeper position. No significant differences were found in BIC
      values (P > 0.05). The total BIC at 8 weeks was (46.22 +/- 4.29%) for the crestal
      group and (49.72 +/- 2.21%) for the subcrestal group; at 12 weeks, it was (41.54
      +/- 3.87%) for the crestal group and (56.87 +/- 3.46%) for the subcrestal group.
      CONCLUSIONS: Within the limitations of this study, the findings suggest that
      apical positioning of the top of the implant does not jeopardize bone crest and
      peri-implant tissue remodeling. However, less resorption of the lingual and
      buccal crest may be expected when implants are placed 2 mm subcrestally, but this
      is not related to implant design. Moreover, implants placed subcrestally produced
      better bone-to-implant contact measurements.

PMID- 24118346
TI  - Turnover in health care: the mediating effects of employee engagement.
AB  - AIM: This study aimed to understand the interaction between interpersonal
      respect, diversity climate, mission fulfilment and engagement to better predict
      turnover in health care. BACKGROUND: Registered nurse turnover has averaged 14%
      and current nursing shortages are expected to spread. Few studies have studied
      employee engagement as a mediator between organisational context and turnover.
      METHOD: Study participants were employees working within 185 departments across
      ten hospitals within a large healthcare organisation in the USA. Although a total
      of 5443 employees work in these departments, employee opinion survey responses
      were aggregated by department before being linked to turnover rates gathered from
      company records. RESULT: Engagement fully mediated the relationship between
      respect and turnover and the relationship between mission fulfilment and
      turnover. Diversity climate was not related to turnover. CONCLUSION: Turnover in
      health care poses a significant threat to the mission of creating a healing
      environment for patients and these results demonstrate that workplace respect and
      connection to the mission affect turnover by decreasing engagement. IMPLICATIONS
      FOR NURSING MANAGEMENT: The findings demonstrated that to increase engagement,
      and improve turnover rates in health care, it would be beneficial for
      organisations, and nurse management to focus on improving mission fulfilment and
      interpersonal relationships.

PMID- 24118347
TI  - Novel evolutionary pathways of sex-determining mechanisms.
AB  - Evolutionary transitions between sex-determining mechanisms (SDMs) are an enigma.
      Among vertebrates, individual sex (male or female) is primarily determined by
      either genes (genotypic sex determination, GSD) or embryonic incubation
      temperature (temperature-dependent sex determination, TSD), and these mechanisms
      have undergone repeated evolutionary transitions. Despite this evolutionary
      lability, transitions from GSD (i.e. from male heterogamety, XX/XY, or female
      heterogamety, ZZ/ZW) to TSD are an evolutionary conundrum, as they appear to
      require crossing a fitness valley arising from the production of genotypes with
      reduced viability owing to being homogametic for degenerated sex chromosomes (YY
      or WW individuals). Moreover, it is unclear whether alternative (e.g. mixed)
      forms of sex determination can persist across evolutionary time. It has
      previously been suggested that transitions would be easy if temperature-dependent
      sex reversal (e.g. XX male or XY female) was asymmetrical, occurring only in the
      homogametic sex. However, only recently has a mechanistic model of sex
      determination emerged that may allow such asymmetrical sex reversal. We
      demonstrate that selection for TSD in a realistic sex-determining system can
      readily drive evolutionary transitions from GSD to TSD that do not require the
      production of YY or WW individuals. In XX/XY systems, sex reversal (female to
      male) occurs in a portion of the XX individuals only, leading to the loss of the
      Y allele (or chromosome) from the population as XX individuals mate with each
      other. The outcome is a population of XX individuals whose sex is determined by
      incubation temperature (TSD). Moreover, our model reveals a novel evolutionarily
      stable state representing a mixed-mechanism system that has not been revealed by
      previous approaches. This study solves two long-standing puzzles of the evolution
      of sex-determining mechanisms by illuminating the evolutionary pathways and
      endpoints. 

PMID- 24118348
TI  - Exposure to an organophosphate pesticide, individually or in combination with
      other Gulf War agents, impairs synaptic integrity and neuronal differentiation,
      and is accompanied by subtle microvascular injury in a mouse model of Gulf War
      agent exposure.
AB  - Gulf War illness (GWI) is a currently untreatable multi-symptom disorder
      experienced by 1990-1991 Persian Gulf War (GW) veterans. The characteristic
      hallmarks of GWI include cognitive dysfunction, tremors, migraine, and
      psychological disturbances such as depression and anxiety. Meta-analyses of
      epidemiological studies have consistently linked these symptomatic profiles to
      the combined exposure of GW agents such as organophosphate-based and pyrethroid
      based pesticides (e.g. chlorpyrifos (CPF) and permethrin (PER) respectively) and
      the prophylactic use of pyridostigmine bromide (PB) as a treatment against
      neurotoxins. Due to the multi-symptomatic presentation of this illness and the
      lack of available autopsy tissue from GWI patients, very little is currently
      known about the distinct early pathological profile implicated in GWI (including
      its influence on synaptic function and aspects of neurogenesis). In this study,
      we used preclinical models of GW agent exposure to investigate whether 6-month
      old mice exposed to CPF alone, or a combined dose of CPF, PB and PER daily for 10
      days, demonstrate any notable pathological changes in hippocampal, cortical
      (motor, piriform) or amygdalar morphometry. We report that at an acute post
      exposure time point (after 3 days), both exposures resulted in the impairment of
      synaptic integrity (reducing synaptophysin levels) in the CA3 hippocampal region
      and altered neuronal differentiation in the dentate gyrus (DG), demonstrated by a
      significant reduction in doublecortin positive cells. Both exposures also
      significantly increased astrocytic GFAP immunoreactivity in the piriform cortex,
      motor cortex and the basolateral amygdala and this was accompanied by an increase
      in (basal) brain acetylcholine (ACh) levels. There was no evidence of microglial
      activation or structural deterioration of principal neurons in these regions
      following exposure to CPF alone or in combination with PB and PER. Evidence of
      subtle microvascular injury was demonstrated by the reduction of platelet
      endothelial cell adhesion molecule (PECAM)-1 levels in CPF+PB+PER exposed group
      compared to control. These data support early (subtle) neurotoxic effects on the
      brain following exposure to GW agents. 

PMID- 24118349
TI  - The prognostic utility of degenerative left shifts in dogs.
AB  - BACKGROUND: A degenerative left shift (DLS) in dogs is reported to be a poor
      prognostic indicator, but no studies have been reported to verify this claim.
      HYPOTHESIS/OBJECTIVES: To characterize the canine population affected by DLS and
      to determine if the presence and severity of the DLS are associated with
      increased risk of euthanasia or death. ANIMALS: Three-hundred and nineteen dogs
      with DLS (cases) and 918 dogs without DLS (controls) presented to the University
      of California, Davis Veterinary Medical Teaching Hospital between April 1, 1995
      and April 1, 2010. METHODS: Retrospective case-control study. All cases had a CBC
      performed within 24 hours of presentation that showed an immature neutrophil
      count higher than the mature neutrophil count. Controls were matched by year of
      presentation and primary diagnosis. Survival analysis was used to determine the
      risk of death or euthanasia associated with DLS and other potential predictors.
      RESULTS: Half of cases versus 76% of controls were alive at discharge. Median in
      hospital survival time was 7 days for cases and 13 days for controls. DLS was a
      significant predictor of death or euthanasia in both univariate and multivariate
      analysis (hazard ratio, HR, 1.9; 95% CI 1.54-2.34). CONCLUSIONS AND CLINICAL
      IMPORTANCE: DLS in dogs is associated with an increased risk of death or
      euthanasia. This finding, however, varies with disease diagnosis and should be
      interpreted in light of the individual patient.

PMID- 24118350
TI  - Small compound bigelovin exerts inhibitory effects and triggers proteolysis of
      E2F1 in multiple myeloma cells.
AB  - Multiple myeloma (MM) is a currently incurable blood cancer. Here we tested the
      effects of a small compound bigelovin on MM cells, and reported that it caused
      cell cycle arrest and subsequently induced apoptosis. Bigelovin triggered
      proteolysis of E2F1, which could be inhibited by caspase inhibitor. To
      investigate the clinical relevance, the expression of E2F1 in MM specimens was
      tested, and the results showed that E2F1 was overexpressed in 25-57% of MM
      patients and was associated with higher International Staging System (ISS) stage.
      These results suggest that E2F1 may be important for MM pathogenesis, and
      bigelovin could serve as a lead compound for the development of E2F1 inhibitor. 

PMID- 24118351
TI  - An exploratory split-face study of a dual-wavelength laser system on
      erythromelanosis follicularis faciei in Chinese population.
AB  - BACKGROUND: Erythromelanosis follicularis faciei (EFF) is clinically
      characterized by well-demarcated erythema, hyperpigmentation and follicular
      papules. No satisfactory therapy has been widely accepted. OBJECTIVE: This study
      was aimed to evaluate the efficiency and complications of a dual-wavelength laser
      system in the treatment of EFF in Chinese population. METHODS: Twelve Chinese
      patients with EFF were enrolled in this study. One side of the face was
      randomized to receive five successions of treatments at intervals of 6-8 weeks,
      with the other side spared as control. The parameters were set as follows: energy
      densities of 6.5-7.5 J/cm(2) with pulsed dye laser (PDL) and 35-50 J/cm(2) with
      Nd:YAG; pulse duration of 0.5 ms with PDL and 15 ms with Nd:YAG; a delay time of
      100 ms between delivery of the two wavelengths. The efficacy was evaluated using
      subjective assessment and non-invasive measurement. RESULTS: After five sessions
      of treatment, over 40% patients achieved more than 50% (moderate or significant)
      improvement. The efficacy maintained at 3-month follow-up. The values of erythema
      index and melanin index on treated side were significantly less than those on
      untreated side after sessions of treatments. Adverse effects of treated side were
      limited. CONCLUSION: Using this split-face module, dual-wavelength laser system
      treatment is proved to be suitable for Chinese EFF. Adverse effects were minimal.

PMID- 24118352
TI  - Pilot study of non-contrast-enhanced MRI vs. ultrasound in renal transplant
      recipients with acquired cystic kidney disease: a prospective intra-individual
      comparison.
AB  - The incidence of renal cell carcinoma (RCC) after kidney transplantation is 15
      fold increased. Acquired cystic kidney disease (ACKD) is one of the known risk
      factors. We performed a small pilot study to assess the role of non-enhanced
      magnetic resonance imaging (MRI) as a tool for intensified screening in renal
      transplant recipients with ACKD. Renal ultrasound was used to assess the native
      kidneys of 215 renal transplant recipients. Thirty patients with 54 kidneys,
      fulfilling the criteria of ACKD, underwent non-enhanced MRI at 1.5T using T2- and
      T1-weighed as well as diffusion-weighted sequences with a high spatial
      resolution. Among the 54 kidneys assessed by both methods, three RCCs were
      identified (6%). Of those, one RCC was detected by both imaging methods (33%),
      while two RCCs were diagnosed by MRI alone (67%). MRI identified an additional
      four proteinaceous or hemorrhagic cysts that did not fulfill the criteria for RCC
      but were classified as suspicious. All of these lesions were stable in size and
      appearance in follow-up studies. In conclusion, non-enhanced MRI was more
      sensitive than ultrasound in identifying RCCs and lesions suspicious for RCC and
      thus appears to be a useful secondary screening tool in patients with ACKD after
      renal transplantation. 

PMID- 24118353
TI  - Exploring the factors associated with youth homelessness and arrests.
AB  - PROBLEM: The high rate of arrests among homeless youths has stimulated a growing
      interest in uncovering the factors associated with police involvement in this
      population. This study explored external factors related to their arrests.
      METHOD: This secondary analysis involved 186 homeless youths. The difference
      between youths who reported arrests and those who did not was examined based on
      the following variables: economic status, meaningful activity, involvement with
      other homeless peers, mental illness, and drug use. FINDINGS: The results of this
      study showed a significant association between drug use and arrests, length of
      time homeless and arrests, and depression and arrests. CONCLUSION: The various
      factors thought to be associated with arrests likely interact with one another,
      making it difficult to directly link a specific behavior to being arrested.

PMID- 24118354
TI  - Acute renal failure associated with vancomycin and beta-lactams for the treatment
      of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime.
AB  - Few data are available on the nephrotoxic potential of vancomycin when combined
      with certain beta-lactam antibiotics for the treatment of osteomyelitis (OM). A
      retrospective cohort study was conducted of all diabetic patients with OM treated
      with vancomycin plus piperacillin-tazobactam (VPT) or vancomycin plus cefepime
      (VC) for at least 72 h at a VA Medical Center between 1 January 2006 and 31
      December 2011. All patients with a creatinine clearance (CrCl) of <= 40 mL/min, a
      blood urea nitrogen/serum creatinine (SCr) ratio of >= 20 : 1 or an absolute
      neutrophil count of <500 cells/mm(3) were excluded. The primary outcome was
      development of acute renal failure (ARF), defined as an increase in SCr of 0.5
      mg/dL or 50% of baseline. One hundred and thirty-nine patients met the inclusion
      criteria; 109 in the piperacillin-tazobactam group and 30 in the cefepime group.
      Among patients receiving VPT, 29.3% (32/109) developed ARF, as compared with
      13.3% (4/30) receiving VC (p 0.099). Among patients receiving high-dose therapy
      (>= 18 g of piperacillin-tazobactam daily or >= 3 g of cefepime daily), 37.5%
      (9/24) receiving VPT and 17.6% (3/17) receiving VC developed ARF (p 0.29). A
      multiple logistic regression analysis identified weight and average vancomycin
      trough as the only significant predictors of ARF; the choice of VPT as therapy
      yielded an OR of 3.45 (95% CI 0.96-12.40; p 0.057). The authors were unable to
      detect a statistically significant difference in ARF between groups; however, the
      power requirement was not met. Further study with a larger patient population
      seems warranted.

PMID- 24118355
TI  - Out-of-hospital traumatic cardiac arrest: an underrecognized source of organ
      donors.
AB  - Whereas the gap between organ supply and demand remains a worldwide concern,
      resuscitation of out-of-hospital traumatic cardiac arrest (TCA) remains
      controversial. The aim of this study is to evaluate, in a prehospital medical
      care system, the number of organs transplanted from victims of out-of-hospital
      TCA. This is a descriptive study. Victims of TCA are collected in the out-of
      hospital cardiac arrest registry of the French North Alpine Emergency Network
      from 2004 to 2008. In addition to the rates of admission and survival, brain-dead
      patients and the organ transplanted are described. Among the 540 resuscitated
      patients with suspected TCA, 79 were admitted to a hospital, 15 were discharged
      alive from the hospital, and 22 developed brain death. Nine of these became
      eventually organ donors, with 31 organs transplanted, all functional after 1
      year. Out-of-hospital TCA should be resuscitated just as medical CA. With a
      steady prevalence in our network, 19% of admitted TCA survived to discharge, and
      11% became organ donors. It is essential to raise awareness among rescue teams
      that out-of-hospital TCA are an organ source to consider seriously.

PMID- 24118356
TI  - Association of MMP but not TIMP-1 gene polymorphisms with recurrent aphthous
      stomatitis.
AB  - OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a common oral inflammatory
      disease induced by genetic and environmental factors. Gelatinases (MMP-2 and MMP
      9) and their natural inhibitor TIMP-1 are active players in the inflammatory
      process. We aimed to determine whether inheritance of specific MMP-2, MMP-9, or
      TIMP-1 gene polymorphisms is associated with RAS susceptibility. SUBJECTS AND
      METHODS: Ninety-six RAS patients and 153 healthy controls were studied. Five
      polymorphisms were genotyped: rs17576, rs3918242, and rs11697325 in MMP-9, MMP-2
      rs2285053, and TIMP-1 rs6609533. Association was assessed by logistic regression
      analysis after adjustment for confounding factors. Linkage disequilibrium (LD)
      was assessed using the Haploview program. RESULTS: MMP-9 rs11697325 was
      significantly associated with RAS, with an increase in the AA genotype in
      patients, determined using chi(2) analysis (OR = 2.3, P = 0.006) and adjusted
      regression analysis (OR = 3.1, P = 0.009). MMP-9 rs11697325 and rs17576 showed
      strong LD (D' = 0.95), with an increase in the AA haplotype (P = 0.023) and a
      decrease in the GA haplotype (P = 0.015) in patients. CONCLUSIONS: This is the
      first study to investigate the association of MMPs or TIMP-1 with RAS. We found a
      significant association between MMP-9 rs11697325 polymorphisms and RAS.
      Confirmatory studies in other populations and functional investigations are
      needed to determine the role of these genes in RAS.

PMID- 24118357
TI  - Quality of different gutta-percha techniques when filling experimental internal
      resorptive cavities: a micro-computed tomography study.
AB  - The purpose of this ex vivo study was to determine the quality of root fillings
      in experimental internal resorptive cavities filled using cold lateral
      condensation (CLC), vertical condensation and Thermafil techniques. Forty-five
      extracted maxillary canine teeth were selected. After root canal instrumentation,
      the roots were sectioned horizontally and experimental internal resorption
      cavities were prepared. The root sections were re-approximated with a luting
      agent and randomly assigned to three groups (n = 15) to be filled using CLC,
      vertical condensation and Thermafil, respectively. Assessment of obturation
      quality in the internal resorptive cavity was performed using a desktop X-ray
      micro focus computed tomography scanner, and the percentage of gutta-percha (GP),
      sealer and voiding was calculated for each specimen. Data were statistically
      analysed using non-parametric tests, with P < 0.05 denoting a statistically
      significant difference. Vertical condensation filled 96.25 +/- 8.31% of the total
      artificial cavity, and was superior to CLC (63.20 +/- 16.87%) and Thermafil
      (59.26 +/- 18.47%). The mean percentage of voids was 3.75 +/- 8.31% in the
      vertical condensation group, 37.09 +/- 17.13% in the CLC group and 41.06 +/-
      18.60% in the Thermafil group. We conclude that obturation of experimental
      resorption cavities is significantly better when using vertical condensation than
      when using other GP-based techniques.

PMID- 24118358
TI  - Skin retraction as a marker for aggressive basal cell carcinoma.

PMID- 24118359
TI  - Inhibition of autophagy augments chemotherapy in human salivary adenoid cystic
      carcinoma.
AB  - Although cisplatin (DDP)-based adjuvant chemotherapy is widely used in the
      treatment of salivary adenoid cystic carcinoma (SACC), SACCs have developed
      resistance to cisplatin, resulting in chemotherapy failure. Autophagy serves as a
      critical adaptive response, which was increased in tumor cells in chemotherapy.
      However, the function of autophagy is not clear in SACC. In this study, apoptosis
      induced by DDP in SACC high metastatic cell line (ACC-M) was revealed using MTT
      assay, flow cytometry, and caspase-3 immunoblotting. The autophagy activation
      induced by DDP treatment was measured by transmission electron microscopy, green
      fluorescent protein-light chain 3 plasmid transfection LC3 immunoblotting and p62
      immunoblotting. 3-methyladenine (3-MA) or small interference RNA targeting beclin
      1 (beclin 1 siRNA) inhibited autophagy and significantly enhanced DDP-induced
      apoptosis. ACC-M xenografts in nude mice further verified the synergistic effect
      of DDP and 3-MA. In conclusion, autophagy activation was caused to protect cancer
      cells from DDP-induced apoptosis and autophagy inhibition could be a promising
      strategy for adjuvant chemotherapy in SACC. 

PMID- 24118360
TI  - Comparison of nurse staffing based on changes in unit-level workload associated
      with patient churn.
AB  - AIM: This analysis compares the staffing implications of three measures of nurse
      staffing requirements: midnight census, turnover adjustment based on length of
      stay, and volume of admissions, discharges and transfers. BACKGROUND: Midnight
      census is commonly used to determine registered nurse staffing. Unit-level
      workload increases with patient churn, the movement of patients in and out of the
      nursing unit. Failure to account for patient churn in staffing allocation impacts
      nurse workload and may result in adverse patient outcomes. METHOD(S): Secondary
      data analysis of unit-level data from 32 hospitals, where nursing units are
      grouped into three unit-type categories: intensive care, intermediate care, and
      medical surgical. RESULT: Midnight census alone did not account adequately for
      registered nurse workload intensity associated with patient churn. On average,
      units were staffed with a mixture of registered nurses and other nursing staff
      not always to budgeted levels. Adjusting for patient churn increases nurse
      staffing across all units and shifts. CONCLUSION: Use of the discharges and
      transfers adjustment to midnight census may be useful in adjusting RN staffing on
      a shift basis to account for patient churn. IMPLICATIONS FOR NURSING MANAGEMENT:
      Nurse managers should understand the implications to nurse workload of various
      methods of calculating registered nurse staff requirements.

PMID- 24118361
TI  - Ostomies in rectal cancer patients: what is their psychosocial impact?
AB  - The resection of a low-lying rectal cancer can lead to the creation of an ostomy
      to discharge fecal material. In view of this reconfiguration of anatomy and life
      changing modification of daily bodily functions, it is not surprising that a
      rapidly growing literature has examined ostomy patients' psychosocial challenges.
      The current study was designed (1) to systematically review the published
      literature on these psychosocial challenges and (2) to explore, in a single
      institution setting, whether medical oncologists appear to acknowledge the
      existence of an ostomy during their post-operative evaluations of rectal cancer
      patients. This systematic review identified that social isolation, sleep
      deprivation; financial concerns; sexual inhibition; and other such issues are
      common among patients. Surprisingly, however, in our review of 66 consecutive
      rectal cancer patients, in 17%, the ostomy was not mentioned at all in the
      medical record during the first medical oncology visit; and, in one patient, it
      was never mentioned at all during months of adjuvant chemotherapy. Even in the
      setting of ostomy complications, the ostomy was not always mentioned. This study
      underscores the major psychosocial issues cancer patients confront after an
      ostomy and suggests that healthcare providers of all disciplines should work to
      remain sensitive to such issues. 

PMID- 24118362
TI  - Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic
      endometrium and ovarian endometrioma of women with advanced stage endometriosis.
AB  - PROBLEM: We evaluated whether the expression of NF-kB p65 subunit is increased in
      the eutopic endometrium and/or in the ovarian endometrioma of women with advanced
      stage endometriosis, and ascertained in vitro effects of proinflammatory
      cytokines on the expression and DNA binding of NF-kB p65 subunit in endometrial
      cells. METHOD OF STUDY: Immunohistochemistry was performed to compare the nuclear
      NF-kB p65 subunit immunoreactivity between women with and without advanced stage
      endometriosis. The nuclear NF-kB p65 subunit expression and DNA binding were also
      analyzed in endometrial cells treated with tumor necrosis factor-alpha (TNF
      alpha) or interleukin-1beta (IL-1beta) utilizing Western blot analysis, enzyme
      linked immunosorbent assay, and electrophoretic mobility shift assay. RESULTS:
      The immunoreactivity of the nuclear NF-kB p65 subunit was significantly increased
      in the eutopic endometrium as well as in the ovarian endometrioma of women with
      endometriosis compared with the controls. In vitro treatment of endometrial cells
      with TNF-alpha and IL-1beta led to a significant increase in nuclear NF-kB p65
      subunit expression and DNA binding. CONCLUSIONS: The nuclear expression of NF
      kappaB p65 is increased in the eutopic endometrium and ovarian endometrioma of
      women with advanced stage endometriosis, which strongly suggests that NF-kB
      signaling plays a crucial role in the pathogenesis and/or pathophysiology of
      endometriosis.

PMID- 24118363
TI  - Characterization of tryptophan aminotransferase 1 of Malassezia furfur, the key
      enzyme in the production of indolic compounds by M. furfur.
AB  - Malassezia yeasts are responsible for the widely distributed skin disease
      Pityriasis versicolor (PV), which is characterized by a hyper- or
      hypopigmentation of affected skin areas. For Malassezia furfur, it has been shown
      that pigment production relies on tryptophan metabolism. A tryptophan
      aminotransferase was found to catalyse the initial catalytic step in pigment
      formation in the model organism Ustilago maydis. Here, we describe the sequence
      determination, recombinant production and biochemical characterization of
      tryptophan aminotransferase MfTam1 from M. furfur. The enzyme catalyses the
      transamination from l-tryptophan to keto acids such as alpha-ketoglutarate with
      Km values for both substrates in the low millimolar range. Furthermore, MfTam1
      presents a temperature optimum at 40 degrees C and a pH optimum at 8.0. MfTam1
      activity is highly dependent on pyridoxal phosphate (PLP), whereas compounds
      interfering with PLP, such as cycloserine (CS) and aminooxyacetate, inhibit the
      MfTam1 reaction. CS is known to reverse hyperpigmentation in PV. Thus, the
      results of the present study give a deeper insight into the role of MfTam1 in PV
      pathogenesis and as potential target for the development of novel PV
      therapeutics. 

PMID- 24118364
TI  - The clinical utility of bone turnover markers in the evaluation of bone disease
      in patients with haemophilia A and B.
AB  - Haemophilia A and B have been associated with increased prevalence of low bone
      mineral density (BMD). However, the utility of bone turnover markers (BTM)
      remains unknown. The aim of this study was to evaluate bone metabolism in men
      with haemophilia and to investigate associations between BTM and bone disease.
      Serum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate
      resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and
      osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone
      formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n
      = 11) were studied. Patients with low BMD had significantly higher b-ALP
      concentrations compared with those with normal BMD (12.8 +/- 1.60 vs. 9.72 +/-
      0.58 MUg/L, P = 0.009), without any differences in the other BTM. NTX-I and CTX-I
      concentrations were negatively associated with oestradiol levels and hip BMD and
      positively with human immunodeficiency virus infection, number of affected joints
      and arthropathy scores. B-ALP and OC concentrations were negatively associated
      with hip BMD, severity of haemophilia and fracture history, and positively with
      the number of affected joints and testosterone concentrations. After multivariate
      analysis, NTX-I levels remained negatively associated with oestradiol levels,
      whereas b-ALP concentrations negatively correlated with the level of physical
      activity and positively with the number of affected joints. Increased bone
      metabolism exists in men with haemophilia and low BMD. Increased b-ALP levels may
      identify patients at high risk for fracture. Increased number of target joints,
      low physical activity and low oestradiol concentrations are independently
      associated with increased bone metabolism.

PMID- 24118365
TI  - Do baseline Cereblon gene expression and IL-6 receptor expression determine the
      response to thalidomide-dexamethasone treatment in multiple myeloma patients?
AB  - Immunomodulatory drugs (IMiDs) are key components of treatment for hematologic
      malignancies, especially multiple myeloma (MM). Cereblon (CRBN) expression was
      described to be essential for the activity of thalidomide. Furthermore, IMiD
      binding to CRBN is cytotoxic to multiple myeloma cells and absence of CRBN
      confers IMiDs resistance. Interleukin-6 (IL-6) is a potent pleiotropic cytokine
      that regulates plasma cell (PC) growth via the IL-6 receptor (IL-6R). IL-6/IL-6R
      autocrine activity is implicated in the development and progression of cancers
      including cervical cancer, prostate cancer, and multiple myeloma. The aim of the
      study was to evaluate CRBN and IL-6R expressions and their impact on clinical
      efficacy of dexamethasone-thalidomide therapy in multiple myeloma (MM) patients,
      in addition to their association with other clinical and prognostic parameters.
      Forty-six newly diagnosed MM patients were enrolled in the study. We measured
      CRBN expression prior to therapy initiation by real-time polymerase chain
      reaction in 46 bone marrow (BM) aspiration samples of patients and controls. In
      addition, IL-6R expression was evaluated on BM biopsies of patients and controls
      by immunohistochemistry (IHC). Twenty-eight males (60.9%) and 18 females (39.1%)
      were enrolled. The mean age was 65.11 +/- 7.3 yr (range 39-77 yr). Median CRBN
      expression in 46 BM samples of MM patients was significantly higher than in
      controls (P < 0.001). Among established prognostic parameters, international
      staging system (ISS), serum beta-2-microglobulin (B2M), and serum albumin
      correlated reversely with CRBN expression. IL-6R expression was significantly
      higher in patients than in controls. IL-6R expression was significantly
      associated with response to treatment (P < 0.001), B2M (P = 0.032), and ISS (P =
      0.028). Strong intensity expression was associated with low CRBN expression (P =
      0.001).In conclusion, CRBN expression may provide a biomarker to predict response
      to IMiD in patients with MM and its high expression can serve as a marker of good
      prognosis. Strong IL-6R expression is associated with poor response to therapy in
      multiple myeloma patients and may be used as a prognostic marker. 

PMID- 24118366
TI  - Diet of the insectivorous bat Pipistrellus nathusii during autumn migration and
      summer residence.
AB  - Migration is widespread among vertebrates, yet bat migration has received little
      attention and only in the recent decades has a better understanding of it been
      gained. Migration can cause significant changes in behaviour and physiology, due
      to increasing energy demands and aerodynamic constraints. Dietary shifts, for
      example, have been shown to occur in birds before onset of migration. For bats,
      it is not known if a change in diet occurs during migration, although breeding
      season-related dietary preference has been documented. It is known that a diet
      rich in fats and the accumulation of fat deposits do increase the flight range of
      migratory bats. Some bat species can be regarded as long-distance migrants,
      covering up to 2000 km between summer and winter roosting areas. Pipistrellus
      nathusii (Vespertilionidae), a European long-distant migrant, travels each year
      along the Baltic Sea from north-eastern Europe to hibernate in central and
      southern Europe. This study presents data on the dietary habits of migrating
      Pipistrellus nathusii compared with those during the breeding season. We analysed
      faecal samples from bats on fall migration caught at the Ornithological Field
      Station in Pape, Latvia and from samples collected in North-Latvian summer
      roosts. We applied both morphological identification and molecular methods, as
      morphological methods also recognize life stages of prey and can contribute
      frequency data. The diets of bats on migration and breeding bats were similar,
      with Diptera and Lepidoptera comprising the major prey categories. However,
      certain prey groups could be explained by the different hunting habitats
      exploited during migration vs. summer residence.

PMID- 24118367
TI  - Fetal intracranial injuries following motor vehicle accidents with airbag
      deployment.
AB  - The effects of airbag deployment in motor vehicle accidents (MVA) on the fetus
      are poorly understood. A 22-year-old woman at 24 weeks of gestation collided with
      a telephone pole while driving. She was restrained and an airbag deployed.
      Although she had no major injuries, she experienced decreased fetal movements.
      Fetal heart rate (FHR) monitoring revealed loss of variability without any
      evidence of abruptio placentae, and 4 days later, the variability spontaneously
      recovered. Two weeks after the MVA, ultrasonography showed unilateral ventricular
      dilatation suggestive of fetal brain injury. Magnetic resonance imaging revealed
      subdural hematoma, intraventricular hemorrhage and cystic lesions, interpreted as
      indirect (hypoxic-ischemic) and direct (hemorrhagic) intracranial injuries. After
      MVA with airbag deployment, FHR monitoring can show a transient loss of
      variability, which may precede the appearance of fetal brain injury. 

PMID- 24118368
TI  - Ceramic implants (Y-TZP): are they a viable alternative to titanium implants for
      the support of overdentures? A randomized clinical trial.
AB  - OBJECTIVE: The objective of this study was to assess 1-year clinical success of
      one-piece zirconia implants compared with similar-design titanium implants, in
      the context of a novel protocol for implant distribution. MATERIALS AND METHODS:
      Twenty-four edentulous participants were randomly allocated to one-piece titanium
      or zirconia implant group. Each participant received four implants in the maxilla
      (mid-palatal and three anterior crestal implants) and three implants in the
      mandible (mid-symphyseal and two bilateral distal implants). Conventional loading
      protocol was followed. Marginal bone remodeling and clinical success of implants
      were evaluated. The data were statistically analyzed, and risk predictors for
      implant failures were evaluated. RESULTS: There was no significant difference in
      the survival rate between the two groups. In the mandible, the survival rate of
      titanium implants was 95.8% vs. 90.9% for the zirconia implants. The
      corresponding values in the maxilla were 71.9% and 55%, respectively. Three
      implants in the zirconia group fractured. Statistically significant less marginal
      bone loss was observed around titanium implants (0.18 mm) compared with the
      zirconia group (0.42 mm). The prediction model revealed a higher risk for implant
      failures in the maxilla (P < 0.0001). CONCLUSION: The outcome of this study
      indicates caution before recommendation can be made for the use of single-piece
      zirconia implants for overdenture support. Their use should be limited to cases
      with proven allergy to titanium. This is mainly due to the increased bone loss
      and higher fracture rate observed for zirconia implants. Future biomaterial
      research should focus on producing surface characteristics on zirconia implants
      with outcomes similar to those established for the optimum osseointegration of
      titanium implants.

PMID- 24118370
TI  - A case of vesicular cutaneous lupus erythematosus in a Border collie successfully
      treated with topical tacrolimus and nicotinamide-tetracycline.
AB  - BACKGROUND: Canine vesicular cutaneous lupus erythematosus (VCLE) is an
      autoimmune skin disease of the Shetland sheepdog and rough collie, which
      manifests as an erosive dermatitis of sparsely haired skin of the ventrum and
      concave pinnae. Reported treatment consists of immunosuppression with
      glucocorticoids alone or in combination with azathioprine, but successful
      treatment is unpredictable. OBJECTIVES: To report on the treatment of VCLE in a
      Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination
      with tetracycline. CASE REPORT: An 8-year-old male neutered Border collie was
      presented with multiple coalescing erosions on the ventral abdomen, groin and
      axillae and ulceration on the oral commissures. Clinical presentation, routine
      diagnostics, histology and immunohistochemistry were consistent with VCLE.
      Remission was achieved with topical 0.1% tacrolimus and combination therapy of
      nicotinamide and tetracycline. CONCLUSION AND CLINICAL IMPORTANCE: This dog
      responded well to treatment with topical 0.1% tacrolimus, nicotinamide
      tetracycline and sun avoidance. Complete remission was achieved after 2.5 months,
      and the dog was lesion free during a 1 year follow-up period.

PMID- 24118369
TI  - Concerns about unintended negative consequences of informing the public about
      multifactorial risks may be premature for young adult smokers.
AB  - BACKGROUND: Many health risks are associated with both genetic and behavioural
      factors. Concerns have been raised that learning about such multifactorial risks
      might have detrimental effects on health-related beliefs, cognitions, and affect.
      However, experimental evidence is sparse. OBJECTIVE: To explore the effects of
      reading an online news article about the discovery of a genetic basis for
      nicotine addiction. METHODS: Smokers (N = 333) were recruited from the psychology
      subject pools of two major universities. Participants were randomly assigned to
      read one of three news articles: one describing a genetic basis for nicotine
      addiction and lung cancer obtained from a national news source, one altered to
      indicate no genetic basis for nicotine addiction and lung cancer, or one
      unrelated attention control. Participants then completed an online questionnaire,
      which assessed smoking-related cognitions and affect, and beliefs about nicotine
      addiction, quitting smoking, and whether the harms of tobacco use are delayed.
      RESULTS: There was no statistically significant influence of experimental
      condition on smoking-related cognitions/affect (ps > .05, eta(2)  < .002),
      beliefs about addiction and quitting (Wilks' lambda = .98, p = .66, eta(2)  =
      .01), or delayed harm (ps > .05, eta(2)  < .002). CONCLUSION: Reading an online
      news article about the presence or absence of a genetic basis for nicotine
      addiction was not found to change smoking-related cognitions/affect or beliefs
      among young adult smokers. Concerns about negative effects of multifactorial risk
      information on health beliefs may be premature. Nevertheless, to effectively
      translate basic genomics research into effective public health practice, further
      research should investigate these issues in different populations, via different
      communication modalities, and for different health outcomes. STATEMENT OF
      CONTRIBUTION: What is already known on this subject? Information about the health
      implications of the interaction between genetics and behaviour is becoming
      prevalent. Learning about these interactions may reduce perceived risk and
      intentions to engage in health behaviours. What does this study add? Informing
      young adult smokers about the genetic basis for nicotine addiction does not
      affect health beliefs negatively. Responses are not moderated by endorsing the
      idea of genetic causation or current/experimenter smoking status.

PMID- 24118371
TI  - The social evolution of dispersal with public goods cooperation.
AB  - Selection can favour the evolution of individually costly dispersal if this
      alleviates competition between relatives. However, conditions that favour
      altruistic dispersal also mediate selection for other social behaviours, such as
      public goods cooperation, which in turn is likely to mediate dispersal evolution.
      Here, we investigate - both experimentally (using bacteria) and theoretically -
      how social habitat heterogeneity (i.e. the distribution of public goods
      cooperators and cheats) affects the evolution of dispersal. In addition to
      recovering the well-known theoretical result that the optimal level of dispersal
      increases with genetic relatedness of patch mates, we find both mathematically
      and experimentally that dispersal is always favoured when average patch occupancy
      is low, but when average patch occupancy is high, the presence of public goods
      cheats greatly alters selection for dispersal. Specifically, when public goods
      cheats are localized to the home patch, higher dispersal rates are favoured, but
      when cheats are present throughout available patches, lower dispersal rates are
      favoured. These results highlight the importance of other social traits in
      driving dispersal evolution. 

PMID- 24118372
TI  - Health-promoting lifestyle behaviours in pregnant women in Turkey.
AB  - This study aims to describe the health-promoting lifestyle behaviours of pregnant
      women. The study was carried out with pregnant women who applied to the
      polyclinics in different maternity and children hospitals located in Adana,
      Turkey, between 1 March and 30 May 2009. The data collection tools used in the
      study were (i) a questionnaire that was used to collect sociodemographic data
      from the participants and (ii) the Health Promoting Lifestyle Profile II (HPLP
      II). The results obtained from the study showed that total HPLP II scores were
      moderate; the highest scores were obtained on the spiritual growth dimension and
      the lowest scores on the physical activity dimension. Pregnant women with older
      age, those with a higher educational level, those with a better socioeconomic
      status and those living in a nuclear family were found to be more likely to have
      health-promoting lifestyles. Health promotion and healthy lifestyle need to be an
      integral part of health services provided for pregnant women. Midwives and nurses
      have prominent roles in encouraging pregnant women to engage in health-promoting
      behaviours. 

PMID- 24118373
TI  - Chemotherapy with cisplatin or carboplatin in combination with etoposide for
      small-cell esophageal cancer: a systemic analysis of case series.
AB  - Chemotherapy has been the first-choice treatment for small-cell esophageal cancer
      (SCEC), etoposide plus cisplatin or carboplatin (EP/CP) is the most commonly
      recommended chemotherapeutical strategy. However, the choice of chemotherapy in
      treating SCEC has not been validated by studies of large cohorts of cases because
      of the rarity of the malignancy, and the efficacy superiority of EP/CP over other
      chemotherapy combinations has not been confirmed. The present case series
      analysis was conducted to address the above issues. Reported studies of SCEC
      patients were retrieved. Case series with more than five patients were enrolled.
      Eight patients treated in our institute were also included as another case
      series. Data pertaining to clinical stages, treatment regimens, and survival time
      were collected and analyzed. Altogether, 19 SCEC case series were enrolled,
      including 164 male and 61 female patients with a median age of 63.5 years. The
      follow-up time ranged from 0.1 to 221 months (median 12.3 months). The median
      survival time (MST) was 19 months for limited disease (LD) patients (124 cases)
      and 9 months for extensive disease (ED) patients (88 cases) (P<0.001). For LD
      patients, MST was obviously prolonged by chemotherapeutical regimens (20 vs. 10
      months, P<0.01), whereas this superiority was not proved in ED patients (10 vs.
      10 months, P>0.05). EP/CP did not result in significantly longer MST, compared
      with that of the cases treated by other chemotherapy combinations (P>0.05, for
      either LD or ED cases). Chemotherapy prolongs the survival time of the LD SCEC
      patients, which indicates that chemotherapeutical treatment is effective for
      SCEC. EP/CP, as commonly recommended multidrug chemotherapy regimen, is not
      superior to other chemotherapy combinations.

PMID- 24118374
TI  - Myeloid sarcoma with megakaryoblastic differentiation mimicking a sellar tumor.
AB  - Myeloid sarcoma (MS) is a localized extra-medullary tumor mass of immature
      myeloid cells, arising de novo or related to acute myeloid leukemia, of which it
      can be a forerunner, a coinciding or late event. Less commonly, MS represents an
      acute blastic transformation of myelodysplastic syndromes or myeloproliferative
      neoplasms. This rare condition commonly consists of a proliferation of more or
      less immature cells with a myeloid immunophenotype, very exceptional cases
      showing a megakaryoblastic or erythroid differentiation. The most common
      localization of MS is the skin, lymph node, soft tissues and bones, but CNS
      involvement is exceedingly rare, with no cases reported in the sellar region. We
      report a 54-year-old man, affected by myeloproliferative neoplasm, JAK2 V617F
      positive of 13 years duration, who acutely presented with a third cranial nerve
      palsy; neuroradiology documented a space-occupying lesion at the level of the
      sellar, upper clival and right parasellar regions, that was sub-totally removed
      with a trans-sphenoidal approach. The histological examination documented a
      proliferation of large, blastic cells, frequently multinucleated; a diagnosis of
      MS with megakaryoblastic differentiation, arising in a background of chronic
      idiopathic myelofibrosis, was suggested by immunohistochemistry, owing to CD42b,
      CD45, CD61 and LAT (linker for activation of T cells) positivity. In addition,
      homozygous JAK2 V617F mutation was detected from the myeloid sarcoma specimen. A
      few weeks after surgery, an acute blastic leukemic transformation occurred and,
      despite chemotherapy, the patient died 2 months after surgery. To the best of our
      knowledge, this is the first MS case with megakaryoblastic differentiation
      arising within the CNS. 

PMID- 24118376
TI  - Anatomical versus electrophysiological isolation approaches to ablate ventricular
      arrhythmias originating from near the coronary artery ostium.

PMID- 24118377
TI  - Methylentetrahydrofolatereductase (rs1801133) polymorphism and psoriasis:
      contribution to oxidative stress, lipid peroxidation and correlation with
      vascular adhesion protein 1, preliminary report.
AB  - BACKGROUND: Psoriatic patients are at greater risk of oxidative stress and
      inflammation which is associated with abnormal plasma lipid metabolism and lipid
      peroxidation.There is not any information about the clinical significance of
      relation between methylentetrahydrofolatereductase (MTHFR) 677-T allele with
      malondialdehyde (MDA), lipids, apolipoproteins and vascular adhesion protein-1
      (VAP-1) partakes in the migration process of lymphocytes into sites of
      inflammation. OBJECTIVES: This study is the first investigation to examine the
      association of MTHFR (rs1801133) C677T polymorphism, serum level of MDA, VAP-1,
      lipid-lipoprotein and apolipoproteins with the risk of psoriasis. METHODS: The
      present case-control study consisted of 100 psoriatic patients and 100 gender-
      and age-matched unrelated healthy controls from west population of Iran. MTHFR
      C677T (rs1801133) polymorphisms were detected by restriction fragment length
      polymorphism (PCR-RFLP), VAP-1 by ELISA, apolipoproteins by immunoprecipitation,
      lipid and apolipoproteins by spectrophotometery and MDA by HPLC. RESULTS: We
      found that dominant/recessive model (CC + CT/TT) and T allele of MTHFR-677
      alleles significantly 7.45 and 1.76 times increased risk of psoriasis,
      respectively. The psoriasis patients with MTHFR-677-T (C/T + T/T) allele had
      significantly higher serum MDA, VAP-1 and apolipoproteinsAPOB concentrations and
      ratio of APOB/APOA1 than the control subjects.The MTHFR-677-T allele frequencies
      in psoriasis patients were significantly higher than that in control group (28.5%
      vs. 18.5%; P = 0.018).We found a significant positive correlation between VAP-1
      with MDA (P = 0.047) and LP (a) (P = 0.025). CONCLUSION: In the present study, we
      demonstrated for the first time that the psoriasis patients with MTHFR-677-T (C/T
      + T/T) allele had higher serum levels of MDA, VAP-1, APOB and ratio of APOB/APOA1
      and dominant/recessive model (CC+CT/TT) and T allele of MTHFR-677 are
      significantly more common in psoriasis and increased risk of psoriasis by 7.45
      and 1.76 fold, respectively. These data suggest that psoriasis patients carrying
      of TT genotypes and T allele of MTHFR-677 may be more susceptible to
      cardiovascular disease and myocardial infarction.

PMID- 24118378
TI  - Clinical and clinicopathological factors associated with survival in 44 horses
      with equine neorickettsiosis (Potomac horse Fever).
AB  - BACKGROUND: The epidemiology of equine neorickettsiosis (EN) has been extensively
      studied but limited clinical and clinicopathological data are available
      concerning naturally infected horses. HYPOTHESIS: Factors predictive of survival
      will be identified in horses diagnosed with EN. ANIMALS: Convenience sample of 44
      horses with EN admitted to 2 referral institutions. METHODS: A retrospective
      study was performed. A diagnosis of EN was based on the presence of positive
      blood or fecal PCR. RESULTS: The most common clinical signs included diarrhea
      (66%), fever (50%), anorexia (45%), depression (39%), colic (39%), and lameness
      (18%). The median duration of hospitalization was 6 days and 73% of horses
      survived to discharge. Laminitis was present in 36% of horses, 88% of which were
      affected in all 4 feet. Serum creatinine and urea nitrogen concentrations, as
      well as RBC count, blood hemoglobin concentration, hematocrit, band neutrophils,
      serum AST activity, serum CK activity, and anion gap, were significantly (P <
      .05) higher in nonsurvivors. Serum chloride and sodium, concentrations as well as
      duration of hospitalization were significantly lower in nonsurvivors. The results
      of forward stepwise logistic regression indicated that blood hemoglobin
      concentration on admission and antimicrobial treatment with oxytetracycline were
      independent factors associated with survival. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Severity of colitis as reflected by electrolyte loss,
      hemoconcentration, and prerenal azotemia were predictors of survival in horses
      diagnosed with EN. Treatment with oxytetracycline was associated with increased
      survival.

PMID- 24118379
TI  - Morphometrical study of minor salivary gland in xerostomic patients with altered
      lipid metabolism.
AB  - OBJECTIVE: To evaluate the correlation between dyslipidemia in patients with oral
      dryness and the development of non-specific histopathological findings in their
      labial salivary gland biopsies. METHODS: Thirty seven patients suffering from
      oral dryness (18 patients with dyslipidemia and 19 age-matched patients with
      normal lipid blood levels) underwent labial salivary gland biopsy. Total acinar
      area (TAA), acinar cell number, acinar lumen area (ALA), duct lumen area (DLA),
      area occupied by cells in acinus (AoCA), and area of one acinar cell (OAC) were
      calculated. RESULTS: A significantly (P < 0.05) increased AoCA, OAC, and DLA in
      labial glands from patients with impaired lipid metabolism, compared to controls,
      were found. CONCLUSION: A positive relationship between dyslipidemia and
      morphological changes in labial salivary glands was obtained.

PMID- 24118381
TI  - Cannabis Use Among High-Risk Youth in Israel (2004-2011): An Examination of
      Gender and Country of Origin Status.
AB  - PROBLEM: Scant knowledge exists about high-risk adolescents who are school
      dropouts in treatment for substance abuse. PURPOSE: This study aims to examine
      the patterns of cannabis (i.e., marijuana and hashish) use among school dropouts
      receiving substance abuse treatment based on their gender and country of origin
      status (i.e., Israeli and former Soviet Union-FSU). METHODS: A total of 628
      dropouts referred to a residential substance abuse treatment facility in Israel
      from 2004 to 2011 were studied. Chi-square and t test analyses were used to
      determine the impact of gender and country of origin status on cannabis use.
      FINDINGS: Significant differences exist for age of first, lifetime, and last 30
      day cannabis use. FSU youths begin cannabis at an earlier age. Cannabis use tends
      to be higher among males and those with Israeli country of origin status.
      Furthermore, cannabis use among dropouts is much higher than those attending
      school. CONCLUSIONS: Gender and country of origin status have implications that
      should be of concern to healthcare professionals treating adolescent substance
      abuse. Further research is needed to validate the study findings both in Israel
      and other countries for policy, training, and treatment purposes.

PMID- 24118380
TI  - HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1
      expression and activates Wnt pathway.
AB  - Long non-coding RNAs (LncRNAs) have been recently found to be pervasively
      transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a
      well-known LncRNA, has been found to play important roles in several tumors.
      Herein, the clinical application value and biological functions of HOTAIR were
      focused and explored in esophageal squamous cell carcinoma (ESCC). It was found
      that there was a great upregulation of HOTAIR in ESCC compared to their adjacent
      normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a
      significantly poorer prognosis than those with low expression. Moreover, HOTAIR
      was further validated to promote migration and invasion of ESCC cells in vitro.
      Then some specific molecules with great significance were investigated after
      HOTAIR overexpression using microarray and quantitative real time-polymerase
      chain reaction (qPCR). WIF-1 playing an important role in Wnt/beta-catenin
      signaling pathway was selected and further tested by immunehistochemistry.
      Generally, inverse correlation between HOTAIR and WIF-1 expression was
      demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly
      decreased WIF-1 expression by promoting its histone H3K27 methylation in the
      promoter region and then activated the Wnt/beta-catenin signaling pathway. This
      newly identified HOTAIR/WIF-1 axis clarified the molecular mechanism of ESCC cell
      metastasis and represented a novel therapeutic target in patients with ESCC. 

PMID- 24118382
TI  - A formula to calculate the standard liver volume in children and its application
      in pediatric liver transplantation.
AB  - Due to a lack of available size-matched liver grafts from children, most
      pediatric recipients are transplanted with technical variant grafts from adult
      donors. Size requirements for these grafts are not well defined, and consequences
      of mismatched graft sizes in pediatric liver transplantation are not known.
      Existing formulas for calculation of a standard liver volume are mostly derived
      from adults disregarding the age-related percentual liver weight changes in
      children. In this study, we aimed to establish a formula for general use in
      children to calculate the standard liver volume. In a second step, the formula
      was applied in pediatric patients undergoing liver transplantation at our
      institution between 2000 and 2010 (n = 377). Analysis of a large number (n = 388)
      of autopsy data from children by regression analysis revealed a best fit for two
      formulas: "Formula 1," children 0 to <=1 year (n = 246): standard liver volume
      [ml] = -143.062973 +4.274603051 * body length [cm] + 14.78817631 * body weight
      [kg]; "Formula 2," children >1 to <16 years (n = 142): standard liver volume [ml]
      = -20.2472281 + 3.339056437 * body length [cm] + 13.11312561 * body weight [kg].
      In comparison with children receiving size-matched organs, we found an elevated
      risk of liver graft failure in children transplanted with a small-for-size graft,
      whereas large-for-size organs seem to have no negative impact.

PMID- 24118375
TI  - Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans.
AB  - By distorting Mendelian transmission to their own advantage, X-linked meiotic
      drive elements can rapidly spread in natural populations, generating a sex-ratio
      bias. One expected consequence is the triggering of a co-evolutionary arms race
      between the sex chromosome that carries the distorter and suppressors
      counteracting its effect. Such an arms race has been theoretically and
      experimentally established and can have many evolutionary consequences. However,
      its dynamics in contemporary populations is still poorly documented. Here, we
      investigate the fate of the young X-linked Paris driver in Drosophila simulans
      from sub-Saharan Africa to the Middle East. We provide the first example of the
      early dynamics of distorters and suppressors: we find consistent evidence that
      the driving chromosomes have been rising in the Middle East during the last
      decade. In addition, identical haplotypes are at high frequencies around the two
      co-evolving drive loci in remote populations, implying that the driving X
      chromosomes share a recent common ancestor and suggesting that East Africa could
      be the cradle of the Paris driver. The segmental duplication associated with
      drive presents an unusual structure in West Africa, which could reflect a
      secondary state of the driver. Together with our previous demonstration of driver
      decline in the Indian Ocean where suppression is complete, these data provide a
      unique picture of the complex dynamics of a co-evolutionary arms race currently
      taking place in natural populations of D. simulans.

PMID- 24118383
TI  - Molecular investigation of menstrual tissue for the presence of Chlamydia
      trachomatis, Ureaplasma urealyticum and Mycoplasma hominis collected by women
      with a history of infertility.
AB  - AIM: At present, routine laboratory investigation of the infectious agents
      implicated in female genital infections is mainly based on culture/direct
      fluorescence antibody (DFA) (immunofluorescence antibody test) results of
      cervicovaginal secretions. In this study the use of the menstrual tissue is
      introduced for the molecular detection of pathogens which are implicated in
      female infertility. MATERIAL AND METHODS: Cervicovaginal secretions and menstrual
      tissue samples of 87 women (mean age 34.07 +/- 5.17) experiencing infertility
      problems were screened for Chlamydia trachomatis, Ureaplasma urealyticum and
      Mycoplasma hominis presence using polymerase chain reaction (PCR, light cycler
      PCR). Cervicovaginal secretions were also tested by the culture/DFA technique.
      The results were compared using the binomial test. RESULTS: In the overall study
      group, the prevalence of C. trachomatis was 25.3%, 18.3%, and 13.8%, the
      prevalence of U. urealyticum was 18.3%, 16.09% and 12.6% and the prevalence of M.
      hominis was 13.7%, 19.5% and 8.0% in the menstrual tissue, cervicovaginal
      secretions using PCR and cervicovaginal secretions culture/DFA, respectively. A
      statistically significant difference was revealed between the two methods for all
      three microbes and between menstrual tissue and cervicovaginal secretions PCR for
      chlamydia. CONCLUSIONS: The use of menstrual tissue along with the PCR method
      seems to be an effective and thus novel alternative for the investigation of the
      infectious agents lying in the genital tract. One of the main advantages of this
      technique compared to cervicovaginal secretions is that it is non-invasive and
      the sample can be collected at home, thus allowing the early detection and
      treatment of a condition that can otherwise lead to serious consequences, such as
      tubal obstruction, pelvic inflammatory disease, ectopic pregnancy, spontaneous
      abortions and unexplained infertility.

PMID- 24118385
TI  - Lymphoedema following treatment for head and neck cancer: impact on patients, and
      beliefs of health professionals.
AB  - Cervicofacial lymphoedema is a recognised side-effect that may result following
      treatment for head and neck cancer. This study aimed to investigate the
      perspectives of affected patients and the beliefs that treating health
      professionals hold about head and neck lymphoedema. Ten patients with head and
      neck lymphoedema and 10 health professionals experienced in the treatment of head
      and neck cancer patients agreed to participate in semi-structured face to face
      interviews. Interviews were recorded, audio files were transcribed and coded and
      then analysed for themes. Themes of experiences of patients with head and neck
      lymphoedema and the beliefs of health professionals largely overlapped. Given its
      visible deformity, the main effect of lymphoedema in head and neck cancer
      patients was on appearance. In some cases this lead to negative psychosocial
      sequelae such as reduced self-esteem, and poor socialisation. Clinicians need to
      be aware of those patients more likely to experience lymphoedema following
      treatment for head and neck cancer, and how they are affected. Understanding how
      patients with facial lymphoedema are affected psychologically and physically, and
      the importance of prompt referral for lymphoedema treatment, might ultimately
      improve outcomes and ensure optimal management. 

PMID- 24118384
TI  - Antibiotic use during pregnancy alters the commensal vaginal microbiota.
AB  - Antibiotics may induce alterations in the commensal microbiota of the birth canal
      in pregnant women. Therefore, we studied the effect of antibiotic administration
      during pregnancy on commensal vaginal bacterial colonization at gestational week
      36. Six hundred and sixty-eight pregnant women from the novel unselected
      Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010 ) pregnancy
      cohort participated in this analysis. Detailed information on oral antibiotic
      prescriptions during pregnancy filled at the pharmacy was obtained and verified
      prospectively. Vaginal samples were obtained at pregnancy week 36 and cultured
      for bacteria. Women who received oral antibiotics during any pregnancy trimester
      had an increased rate of colonization by Staphylococcus species in the vaginal
      samples as compared with samples obtained from women without any antibiotic
      treatment during pregnancy (adjusted OR 1.63, 95% CI 1.06-2.52, p 0.028). Oral
      antibiotic administration in the third trimester were also associated with
      increased colonization by Staphylococcus species (adjusted OR 1.98, 95% CI 1.04
      3.76, p 0.037). These bacteriological changes were associated with urinary tract
      infection antibiotics. Women treated in the third trimester of pregnancy were
      more often colonized by Escherichia coli than women without antibiotic treatment
      in the third trimester (adjusted OR 1.91, 95% CI 1.04-3.52, p 0.038). This change
      was associated with respiratory tract infection (RTI) antibiotics. We did not
      observe any significant changes in vaginal Streptococcus agalactiae (group B
      streptoccocus) or Staphylococcus aureus colonization following antibiotic
      treatment in pregnancy. Antibiotic administration during pregnancy leads to
      alterations in the vaginal microbiological ecology prior to birth, with potential
      morbidity, and long-term effects on the early microbial colonization of the
      neonate.

PMID- 24118386
TI  - Protection against a fungal pathogen conferred by the aphid facultative
      endosymbionts Rickettsia and Spiroplasma is expressed in multiple host genotypes
      and species and is not influenced by co-infection with another symbiont.
AB  - Many insects harbour facultative endosymbiotic bacteria, often more than one type
      at a time. These symbionts can have major effects on their hosts' biology, which
      may be modulated by the presence of other symbiont species and by the host's
      genetic background. We investigated these effects by transferring two sets of
      facultative endosymbionts (one Hamiltonella and Rickettsia, the other
      Hamiltonella and Spiroplasma) from naturally double-infected pea aphid hosts into
      five novel host genotypes of two aphid species. The symbionts were transferred
      either together or separately. We then measured aphid fecundity and
      susceptibility to an entomopathogenic fungus. The pathogen-protective phenotype
      conferred by the symbionts Rickettsia and Spiroplasma varied among host
      genotypes, but was not influenced by co-infection with Hamiltonella. Fecundity
      varied across single and double infections and between symbiont types, aphid
      genotypes and species. Some host genotypes benefit from harbouring more than one
      symbiont type. 

PMID- 24118387
TI  - Opposing effects on immune function and skin barrier regulation by the proteasome
      inhibitor bortezomib in an allergen-induced eczema model.
AB  - Proteasome inhibition (PI) has been reported to interfere with antibody-driven
      autoimmune diseases. The impact of PI on the allergic immune response and on skin
      diseases like atopic dermatitis (AD) has not been thoroughly explored, however.
      Here, we examined whether the PI bortezomib interferes with the allergic immune
      response and the severity of AD by using an established mouse model of allergen
      driven dermatitis, to which bortezomib was applied after the establishment of
      systemic sensitization to ovalbumin. The treatment indeed resulted in a
      remarkable decrease in total and allergen-specific plasma cells/antibody
      secreting cells, as evidenced by flow cytometry and ELISpot, respectively. This
      was accompanied by rapid reductions in serum antibody titres, including a
      prominent reduction of the IgE isotype. CD4+ and CD8+ cells were greatly
      diminished in lesional skin on immunohistological staining. The impressive
      effects at the level of immune modulation did not result in any improvement in
      the eczema, however. Following up on this unexpected result, we found that the
      skin itself was susceptible to bortezomib, by which it was instructed to lower
      the expression of critical skin barrier genes, especially transglutaminase-1 and
      filaggrin. Together, bortezomib eliminates plasma cells and decreases
      immunoglobulin responses, including allergenic IgE. Although anti-inflammatory
      effects are detectable in the skin, counter-regulatory effects from PI on
      resident skin cells likely undermine improvement in the eczema. These results
      caution against the therapeutic use of bortezomib for inflammatory skin
      disorders, which are characterized by inherently impaired barrier function,
      especially AD. 

PMID- 24118388
TI  - In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and
      suppresses tumor growth in ovarian cancer.
AB  - Vasohibin-2 (VASH2) is a homolog of vasohibin-1 and exhibits pro-angiogenic
      activity. We recently reported that VASH2 is expressed in certain ovarian cancers
      and promotes tumor growth through angiogenesis. To further demonstrate the
      effectiveness of molecular targeting of VASH2 for anticancer treatment, we
      applied in vivo delivery of siRNA targeting VASH2 (siVASH2) using atelocollagen
      to a xenograft model of ovarian cancer. We inoculated mice s.c. with DISS and
      SKOV-3, two representative human ovarian serous adenocarcinoma cell lines. When
      tumors were measurable, we initiated treatment with control or siVASH2 mixed with
      atelocollagen, which enveloped the whole tumor. Treatment with siVASH2
      significantly inhibited s.c. tumor growth by abrogating tumor angiogenesis. We
      confirmed that expression of VASH2 mRNA in the tumor was downregulated by siVASH2
      treatment. In addition, the siVASH2-treated tumor contained more blood vessels
      covered with pericytes, indicating that knockdown of VASH2 contributes to the
      normalization of tumor blood vessels. Based on these results, VASH2 may be a
      promising molecular target for ovarian cancer treatment. 

PMID- 24118389
TI  - Immunosuppression after renal allograft failure: a survey of US practices.
AB  - BACKGROUND: Little data exist to guide the management of immunosuppression after
      renal graft failure. More aggressive tapering of immunosuppressive medications
      may reduce the risk of infection, but may increase the risk of rejection and
      sensitization. METHODS: To document current practices in the US, we emailed a
      questionnaire to medical and surgical transplant directors as identified by the
      United Network for Organ Sharing (UNOS). RESULTS: Emails were sent to 221
      programs, of which 93 (42.1%) responded. About 24.7% of respondents reported
      adjusting immunosuppression according to a standard protocol; 75.3% said
      practices are physician dependent. The majority said that 80 or 100% of patients
      are off all immunosuppression one yr after returning to dialysis. The most
      important factors cited in deciding whether to stop immunosuppression were plans
      to retransplant (40.2%) and signs and symptoms of rejection (37.0%). When asked
      which immunosuppressive medications are continued indefinitely, 21.5% responded
      prednisone and 71.0% said none. Respondents most commonly said they performed
      graft nephrectomy only if there are signs and symptoms of rejection (47.3%) or if
      signs and symptoms of rejection fail to respond to steroids (34.4%). CONCLUSIONS:
      In the absence of good data to guide decisions on immunosuppression in patients
      with failed allografts, practices in the US vary greatly. More data are needed to
      determine which policies lead to the best outcomes.

PMID- 24118391
TI  - Genetic consequences of breaking migratory traditions in barnacle geese Branta
      leucopsis.
AB  - Cultural transmission of migratory traditions enables species to deal with their
      environment based on experiences from earlier generations. Also, it allows a more
      adequate and rapid response to rapidly changing environments. When individuals
      break with their migratory traditions, new population structures can emerge that
      may affect gene flow. Recently, the migratory traditions of the Barnacle Goose
      Branta leucopsis changed, and new populations differing in migratory distance
      emerged. Here, we investigate the population genetic structure of the Barnacle
      Goose to evaluate the consequences of altered migratory traditions. We used a set
      of 358 single nucleotide polymorphism (SNP) markers to genotype 418 individuals
      from breeding populations in Greenland, Spitsbergen, Russia, Sweden and the
      Netherlands, the latter two being newly emerged populations. We used discriminant
      analysis of principal components, FST , linkage disequilibrium and a comparison
      of geneflow models using migrate-n to show that there is significant population
      structure, but that relatively many pairs of SNPs are in linkage disequilibrium,
      suggesting recent admixture between these populations. Despite the assumed
      traditions of migration within populations, we also show that genetic exchange
      occurs between all populations. The newly established nonmigratory population in
      the Netherlands is characterized by high emigration into other populations, which
      suggests more exploratory behaviour, possibly as a result of shortened parental
      care. These results suggest that migratory traditions in populations are subject
      to change in geese and that such changes have population genetic consequences. We
      argue that the emergence of nonmigration probably resulted from developmental
      plasticity. 

PMID- 24118390
TI  - Establishment and characterization of a primary calcifying epithelial odontogenic
      tumor cell population.
AB  - Calcifying epithelial odontogenic tumors (CEOTs) are rare neoplasms derived from
      dental tissue with the unique characteristic of calcifying amyloid-like material.
      OBJECTIVES: To establish primary CEOT epithelial-derived cell populations,
      investigate the expression of enamel matrix proteins (EMPs), and identify
      potential ameloblastin (AMBN) and patched 1 (PTCH1) gene alterations. MATERIALS
      AND METHODS: A 28-year-old patient with a lesion of the posterior maxilla,
      radiographically characterized by a radiolucency with well-defined borders
      containing mixed radiopacities, agreed to participate with informed consent. The
      patient's biopsy confirmed the diagnosis of CEOT, and a small representative
      tumor fragment was ascertained for cell culture. Explant cultures were
      established and used to establish primary cell populations. These were analyzed
      for morphology, cell proliferation, mineralization activity, expression of
      epithelial-associated markers (qRT-PCR and immunocytochemistry), and gene
      mutations of AMBN or PTCH1. DNA was extracted from tumor cells and gene coding
      and exon-intron boundaries overlapping fragments amplified. PCR products were
      bidirectional DNA sequenced and compared against reference sequence. RESULTS: A
      CEOT cell population was established and proliferated in culture and could be
      maintained for several passages. Expression of EMPs, cytokeratin 14 and 17, and
      patched (PTCH1), as well as ALP activity, was detected. These cells also had the
      ability to mineralize, similar to the primary tumor. Two AMBN alterations were
      identified in the sample: c.1323G>A/A441A (rs7680880) and c.1344*+111delA. Two
      single-nucleotide polymorphisms were identified in the PTCH1 gene. CONCLUSIONS:
      Our data support the establishment of a CEOT-derived cell population, which
      expresses known epithelial-associated proteins.

PMID- 24118392
TI  - Histologic and histomorphometric evaluation of peri-implant bone of immediate or
      delayed occlusal-loaded non-splinted implants in the posterior mandible--an
      experimental study in monkeys.
AB  - OBJECTIVES: The primary aim of this study was to compare the bone reaction around
      immediate-loaded non-splinted single implants vs. delayed loaded non-splinted
      single implants placed in healed ridges in the posterior mandible. MATERIALS AND
      METHODS: Six adult Macaca Fascicularis monkeys were used in this study. The first
      and second premolars and the first molar were extracted in both sides of the
      mandible. After 3 months of healing, four implants (Replace Select Tapered; Nobel
      Biocare, Gothenburg, Sweden) with a moderately rough surface (TiUnite, Nobel
      Biocare) were placed in the edentulous areas of each monkey, two in each side.
      The implants had a length of 10 mm and a diameter of 3.5 mm. Four groups of
      varying time and occlusal loading aspects were created: (i) control group:
      implant placed non-loaded for 3 months; (ii) immediate loaded: implant placed and
      loaded immediately for 3 months; (iii) immediate loaded: implant placed and
      loaded immediately for 6 months; and (iv) delayed loaded: implant placed
      submerged for 3 months and then loaded for 3 months. At the loaded implants,
      after a second stage surgery, a composite crown was made directly on an abutment
      mounted on the implant reinsuring simultaneous occlusal contact on the implant
      crown and the neighboring teeth. After euthanization of the animals, histologic
      specimens were quantified in the light microscope. RESULTS: All implants were
      clinically, radiographically, and histologically osseointegrated at the time of
      euthanization and with only mild signs of inflammation in the peri-implant
      mucosa. The histologic marginal bone level was located on average 1.14-1.74 mm
      apical to the margin of the implants in the various groups. The average bone-to
      implant contact (BIC) varied between 55% and 65% and the average bone density
      (i.e., the proportion of mineralized bone tissue from the implant surface and to
      a distance of 1 mm lateral to the implant) varied between 30.6% and 34.2%. No
      statistical significant differences between groups were observed in the above
      stated histomorphometric parameters. CONCLUSIONS: Similar histologic and
      histomorphometric findings were observed in immediately and delayed loaded non
      splinted implants placed in the posterior mandible of macaque monkeys.

PMID- 24118393
TI  - Variation at phenological candidate genes correlates with timing of dispersal and
      plumage morph in a sedentary bird of prey.
AB  - Polymorphic genes involved in the conserved molecular signalling of circadian and
      circannual clocks may play important roles in governing the timing of breeding
      and dispersal and thereby affect fitness in vertebrates. However, relatively few
      studies have explored associations between phenological candidate genes and
      behaviour, and these are somewhat biased towards particular taxonomic groups such
      as passerine birds and salmonid fish. Consequently, we assayed microsatellite
      polymorphisms within the exonic and 3' untranslated regions of the regulatory
      genes CLOCK, NPAS2, ADCYAP1 and CREB1 in the common buzzard (Buteo buteo), a
      polymorphic raptor species with three plumage morphs that differ in key life
      history traits including lifetime reproductive success. In contrast to studies of
      passerines, CLOCK poly-glutamine (poly-Q) was found to be monomorphic in 976
      common buzzard nestlings as well as in three other Buteo species. Moreover, none
      of the candidate genes were significantly associated with fledging dates,
      although intermediately melanized females were found to lay earlier on average
      than light or dark morph individuals, and their offspring carried longer ADCYAP1
      alleles. In contrast, all three candidate genes explained significant variation
      in one or more measures of juvenile buzzard dispersal (resighting probability,
      timing of dispersal and distance dispersed). Our findings contribute towards a
      broader body of work on the adaptive significance of CLOCK polymorphism, while
      also building upon previous studies that have documented links between ADCYAP1
      variability and the timing of migration. 

PMID- 24118394
TI  - Muricholic bile acids are potent regulators of bile acid synthesis via a positive
      feedback mechanism.
AB  - OBJECTIVE: Bile acid (BA) synthesis is regulated by negative feedback end-product
      inhibition, initiated by farnesoid X receptors (FXRs) in liver and gut. Studies
      on cholic acid (CA)-free Cyp8b1(-/-) mice have concluded that CA is a potent
      suppressor of BA synthesis. Cyp8b1(-/-) mice have increased BA synthesis and an
      enlarged BA pool, a phenotype shared with bile-duct-ligated, antibiotics
      administered and with germ-free mice. Studies on such mice have concluded BA
      synthesis is induced due to reduced hormonal signalling by fibroblast growth
      factor (FGF)15 from intestine to liver. A mutual finding in these models is that
      potent FXR-agonistic BAs are reduced. We hypothesized that the absence of the
      potent FXR agonist deoxycholic acid (DCA) may be important for the induction of
      BA synthesis in these situations. DESIGN: Two of these models were investigated,
      antibiotic treatment and Cyp8b1(-/-) mice and their combination. Secondary BA
      formation was inhibited by ampicillin (AMP) given to wild-type and Cyp8b1(-/-)
      mice. We then administered CA, chenodeoxycholic acid (CDCA) or DCA to AMP-treated
      Cyp8b1(-/-) mice. RESULTS: Our data show that the phenotype of AMP-treated wild
      type mice resembles that of Cyp8b1(-/-) mice with fourfold induced Cyp7a1
      expression, increased intestinal apical sodium-dependent BA transporter
      expression and increased hepatic BA levels. We also show that reductions in the
      FXR-agonistic BAs CDCA, CA, DCA or lithocholic acid cannot explain this
      phenotype; instead, it is likely due to increases in levels of alpha- and beta
      muricholic BAs and ursodeoxycholic acid, three FXR-antagonistic BAs. CONCLUSIONS:
      Our findings reveal a potent positive feedback mechanism for regulation of BA
      synthesis in mice that appears to be sufficient without endocrine effects of
      FGF15 on Cyp7a1. This mechanism will be fundamental in understanding BA
      metabolism in both mice and humans.

PMID- 24118395
TI  - Fundoplication for gastroesophageal reflux disease: regional variability and
      factors predicting operative approach.
AB  - We have recently shown that the majority of patients undergoing fundoplication in
      the United States are women. Based on these findings, we hypothesized that
      nonbiological factors contribute to the decisions on surgical reflux therapy.
      Using State Inpatient Databases of the Agency for Healthcare Research and
      Quality, we extracted annual fundoplication rates, sex distribution, age cohorts,
      racial background, and insurance coverage. To account for potential differences
      in state populations, the results were normalized and correlated with Census
      data, adult obesity rates, median income, poverty rates, and physician workforce
      within the state. Fundoplication rates varied fivefold between states, ranging
      from 4.1+/-0.1 per 100,000 in New Jersey to 21.8+/-0.4 per 100,000 in Oregon.
      Higher poverty rates and a higher fraction of Caucasians within a state
      independently predicted higher fundoplication rates. While the majority of
      operations were performed laparoscopically, surgical approaches also differed
      between states with rates of laparoscopic ranging from 52.3+/-1.8% in Oklahoma to
      87.4+/-1.7% in Hawaii. A lower number of pediatric and Medicaid-insured patient
      and a higher fraction of privately insured patients best predicted higher rates
      of laparoscopic surgery. Our study shows significant regional variation in
      surgical reflux management, which cannot be explained by differences in disease
      mechanisms. Insurance coverage and racial background influenced the likelihood of
      surgery, suggesting a role of financial incentives.

PMID- 24118396
TI  - Does renal denervation target the substrate or the trigger for ventricular
      arrhythmias?

PMID- 24118397
TI  - Infiltrative recurrent eccrine spiradenoma of the anterior neck treated using
      Mohs micrographic surgery.

PMID- 24118398
TI  - Characterization of F8 defects in haemophilia A in Pakistan: investigation of
      correlation between mutation type and the in vitro thrombin generation assay.
AB  - Hereditary haemophilia A is an X-linked bleeding disorder caused by mutations in
      the coagulation factor VIII gene (FVIII abbreviates protein, gene symbol F8). The
      mutation spectrum has been reported in various populations but not in Pakistan.
      The aims of this study were to (i) characterize F8 mutations in a large
      haemophilia A cohort from Pakistan and to (ii) investigate whether in vitro
      thrombin generation (TG) differs according to mutation type (null compared with
      missense) in severe haemophilia A. One hundred individuals diagnosed with
      haemophilia A and 100 healthy controls were recruited in Pakistan. Phenotypic
      measurements were re-evaluated in Cardiff; the essential regions of F8 were
      screened for the causative defect. A diagnosis of haemophilia A was confirmed for
      92 individuals, 7 were found to have haemophilia B and 1 did not have
      haemophilia. The F8 defects were characterized for 80 of the 92 haemophilia A
      individuals and comprised point mutations, inversions (intron 22 and intron 1)
      and frameshifts. Point mutations (41%) were the most frequent, followed by the
      intron 22 inversion (20%). Thirty novel variants were identified. Comparison of
      in vitro TG parameters [velocity index (VI) and peak] was made between severe
      individuals who had a null mutation (no FVIII) and those with a missense change
      (dysfunctional FVIII), no significant difference was observed. The spectrum of F8
      defects in Pakistan is heterogenous; VI and peak in severe haemophilia A are not
      influenced by whether the underlying mutation gives rise to dysfunctional FVIII
      or no coagulation factor at all.

PMID- 24118399
TI  - Factors that predict poor clinical course among patients hospitalized with pelvic
      inflammatory disease.
AB  - AIM: The aim of this study was to identify factors that can predict clinical
      course among patients hospitalized with pelvic inflammatory disease (PID).
      METHODS: Ninety-three patients who needed hospitalization with a diagnosis of PID
      were retrospectively studied. Patients who were discharged within 7 days by
      conservative treatment were defined as favorable course cases (n = 44). Patients
      who needed more than 7 days of hospitalization and/or surgery were defined as
      poor course cases (n = 49). Twenty variables were evaluated by univariate and
      logistic regression analysis: age, history of pregnancy/delivery, gynecological
      open/laparoscopic surgery, PID, oral contraceptives/intrauterine device use and
      intrauterine operation before onset, body temperature, signs of peritoneal
      irritation, vomiting/diarrhea, abnormal vaginal discharge,
      endometriosis/fibroid/adenomyosis/any cystic lesion detected by ultrasonography,
      white blood cell counts/C-reactive protein (CRP) levels . The cut-off value was
      calculated by receiver-operator curve (ROC) analysis. RESULTS: Factors associated
      with poor clinical course were advanced age (P < 0.01), history of gynecological
      open surgery (P < 0.05), any cystic lesion detected by ultrasonography (P < 0.05)
      and high CRP levels (P < 0.05). High CRP levels and intrauterine operation before
      onset were independently associated with poor clinical course. The cut-off value
      for CRP was 4.4 mg/dL. CONCLUSION: This study identified variables that can
      predict poor clinical course of PID. These results can assist gynecologists with
      identifying patients at risk and optimizing the choice of management.

PMID- 24118400
TI  - Entrapment of the inferior horns of the lateral ventricle with enlargement of the
      bilateral choroid plexus.

PMID- 24118401
TI  - An in vitro study to determine the minimal bactericidal concentration of sodium
      hypochlorite (bleach) required to inhibit meticillin-resistant Staphylococcus
      pseudintermedius strains isolated from canine skin.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus pseudintermedius (MRSP) is
      becoming a more common pathogen in animals treated in veterinary hospitals,
      raising concerns for transmission and possible contamination of the hospital
      itself. The identification of effective agents for the decontamination of
      veterinary patients and hospitals is crucial. Sodium hypochlorite (6.15%) or
      'bleach' is an inexpensive and frequently used decontamination agent in human and
      veterinary hospitals and an adjunctive treatment for human patients. There are no
      published data on the minimal bactericidal concentration (MBC) of sodium
      hypochlorite (6.15%) for MRSP. HYPOTHESIS/OBJECTIVES: The objective of this study
      was to determine the MBC of sodium hypochlorite (6.15%) against MRSP strains
      isolated from canine skin. METHODS: In this in vitro study, 12 canine skin
      isolates were obtained from the Antech Diagnostics microbiology department.
      Twofold serial dilutions of sodium hypochlorite (6.15%) were allowed to react
      with each of the MRSP strains for 15 min, followed by overnight incubation on
      agar plates. Colonies on each plate were counted. This process was repeated in
      triplicate. RESULTS: The overall MBC for the canine skin-isolated MRSP strains
      was 1:32, but most strains had an MBC between 1:64 and 1:128 dilution.
      CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows that sodium hypochlorite
      (6.15%) is an effective agent for decontamination at easily achievable
      concentrations.

PMID- 24118402
TI  - Vertebral body infarct and ventral cauda equina enhancement: two confirmatory
      findings of acute spinal cord infarct.
AB  - Two valuable confirmatory MRI findings of acute spinal cord infarct are
      highlighted and discussed: concomitant vertebral body infarct and ventral cauda
      equina nerve root enhancement. 

PMID- 24118403
TI  - Light-dependent, plastome-wide association of the plastid-encoded RNA polymerase
      with chloroplast DNA.
AB  - Plastid genes are transcribed by two types of RNA polymerases: a plastid-encoded
      eubacterial-type RNA polymerase (PEP) and nuclear-encoded phage-type RNA
      polymerases (NEPs). To investigate the spatio-temporal expression of PEP, we
      tagged its alpha-subunit with a hemagglutinin epitope (HA). Transplastomic
      tobacco plants were generated and analyzed for the distribution of the tagged
      polymerase in plastid sub-fractions, and associated genes were identified under
      various light conditions. RpoA:HA was detected as early as the 3rd day after
      imbibition, and was constitutively expressed in green tissue over 60 days of
      plant development. We found that the tagged polymerase subunit preferentially
      associated with the plastid membranes, and was less abundant in the soluble
      stroma fraction. Attachment of RpoA:HA to the membrane fraction during early
      seedling development was independent of DNA, but at later stages of development,
      DNA appears to facilitate attachment of the polymerase to membranes. To survey
      PEP-dependent transcription units, we probed for nucleic acids enriched in
      RpoA:HA precipitates using a tobacco chloroplast whole-genome tiling array. The
      most strongly co-enriched DNA fragments represent photosynthesis genes (e.g.
      psbA, psbC, psbD and rbcL), whose expression is known to be driven by PEP
      promoters, while NEP-dependent genes were less abundant in RpoA:HA precipitates.
      Additionally, we demonstrate that the association of PEP with photosynthesis
      related genes was reduced during the dark period, indicating that plastome-wide
      PEP-DNA association is a light-dependent process.

PMID- 24118404
TI  - Progressive multifocal leukoencephalopathy: a rare infectious complication
      following allogeneic hematopoietic cell transplantation (HCT).
AB  - Progressive multifocal leukoencephalopathy (PML), a demyelinating disorder caused
      by brain infection with JC virus, is a neurological complication of
      immunocompromised states and immunosuppressive therapies. While most commonly
      seen in the HIV/AIDS population, patients with hematologic malignancies are also
      at risk following treatment protocols including monoclonal antibodies such as
      rituximab and after hematopoietic stem cell transplantation. Here, we present the
      case of PML following allogeneic HCT that highlights potential diagnostic
      difficulties. We also review the literature regarding PML following HCT and
      described therapies employed to attempt to treat this disorder. 

PMID- 24118405
TI  - Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol
      withdrawal and support its role in voluntary ethanol consumption.
AB  - Association studies implicate multiple PDZ domain protein (MPDZ/MUPP1) sequence
      and/or expression in risk for alcoholism in humans and ethanol withdrawal (EW) in
      mice, but confirmation has been hindered by the dearth of targeted genetic
      models. We report the creation of transgenic (MPDZ-TG) and knockout heterozygote
      (Mpdz(+/-) ) mice, with increased (2.9-fold) and decreased (53%) target
      expression, respectively. Both models differ in EW compared with wild-type
      littermates (P <= 0.03), providing compelling evidence for an inverse
      relationship between Mpdz expression and EW severity. Additionally, ethanol
      consumption is reduced up to 18% (P = 0.006) in Mpdz(+/-) , providing the first
      evidence implicating Mpdz in ethanol self-administration. 

PMID- 24118406
TI  - Subungual squamous cell carcinoma and exostosis in third toe--case report and
      literature review.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) in the ungual apparatus is a rare
      neoplasia. Although it is the most prevalent malignant tumour in this region, its
      diagnosis is often delayed because it is likened to benign or infectious
      processes. OBJECTIVES: Present a case of SCC with subungual location in a toe,
      and carry out a review of the literature in relation to the most important
      aspects of subungual SCC in toes. METHODS: We describe the case of a white woman
      aged 72, with SCC located in the pulp and in the distal area of the nail bed of
      the third toe, associated with subungual exostosis. The literature on SCC in the
      subungual area of toes, in all its forms under clinical or histopathological
      presentation, is reviewed by means of a search involving Medline, PubMed, and
      Google Academic, from January 1994 to December 2011. RESULTS: Only 36 cases of
      subungual SCC in toes were reported in the 18 years that were reviewed. The
      average age of cases reviewed was 58.92, and the male-to-female ratio was 2:1.
      The most affected toe is the hallux, in 69.4% of cases. In 50% of cases,
      aetiology is unknown or indeterminate; in 22.3% of cases, aetiology is
      metastatic; and in 19.5% of cases, it is associated with human papillomavirus
      (HPV). In 58.2% of cases, partial or total resection of the distal phalanx was
      carried out, of the entire toe, or of the osseous ray of the foot. CONCLUSIONS:
      Chronic tissue irritation caused by microtrauma associated with subungual
      exostosis is the most probable aetiology of the case presented.

PMID- 24118407
TI  - Novel modification of B-Lynch uterine compression sutures for management of
      atonic postpartum hemorrhage: VV uterine compression sutures.
AB  - AIM: The aim of this study was to demonstrate a novel modification of uterine
      compression sutures for use in women with primary postpartum hemorrhage and to
      evaluate its effectiveness. MATERIAL AND METHODS: This was a prospective
      observational study. Nineteen patients with atonic postpartum hemorrhage were
      subjected to the novel VV uterine compression sutures at the time of cesarean
      delivery. RESULTS: The procedure was successful in 18 out of 19 women (94.7%) in
      controlling the bleeding and preserving the patient's uterus. Only one patient
      required supravaginal hysterectomy. CONCLUSIONS: VV compression sutures comprise
      an easy, safe and effective procedure that can be applied in cases of atonic
      postpartum hemorrhage.

PMID- 24118408
TI  - Physical activity levels and torso orientations of hospitalized patients at risk
      of developing a pressure injury: an observational study.
AB  - Pressure injury guidelines recommend regular repositioning yet patients' mobility
      and repositioning patterns are unknown. An observational study using activity
      monitors was undertaken to describe the 24 h activity patterns of 84 hospitalized
      patients at risk of developing a pressure injury. The vast majority of
      participants' time was spent in the sedentary activity range (94% +/- 3%)
      followed by the light range (5% +/- 4 %). Patients changed their posture a median
      of 94 (interquartile range 48) time in the 24-h period (range 11-154), or ~ 3.8
      times per hour. Although a main focus for pressure injury prevention has been on
      repositioning, this study shows that patients with restricted mobility are
      actually moving quite often. Therefore, it might be appropriate to focus more
      attention on other pressure injury prevention strategies such as adequate
      nutrition, appropriate support surfaces and good skin care. 

PMID- 24118409
TI  - Financial and medico-legal implications of late-start dialysis: understanding the
      present policies through a window of past performance.
AB  - In the United States, multiple stakeholders have impacted the timing of dialysis
      initiation for patients with end-stage renal disease. The optimal policy to start
      dialysis for this vulnerable population remains unknown. Historically, patients
      initiated dialysis weeks after the appearance of uremic symptoms. This changed
      not only due to an evolution in medical providers' practice but also due to
      changes in the care delivery system, the political imperatives, and the economic
      driving forces surrounding the care of these patients. One large randomized
      control trial looked at patient outcomes with strategies of early versus late
      start. The trial included an economic analysis. Depending on the specific
      comparison, cost was either lower in the late-start group or was equivalent
      between groups. This result would tend to favor a late-start strategy, where
      patients had an additional 6 months of dialysis-free time. However, the
      generalizability of this analysis has been questioned. Future care models that
      would include patients before and after dialysis initiation would be ideal to
      study cost and quality at the time of this transition of care. The recently
      implemented CMS Quality Incentive Program is one mechanism that could use such
      findings to implement a high-value strategy for patients starting chronic
      dialysis therapies.

PMID- 24118410
TI  - Requirement of essential Pbp2x and GpsB for septal ring closure in Streptococcus
      pneumoniae D39.
AB  - Bacterial cell shapes are manifestations of programs carried out by multi-protein
      machines that synthesize and remodel the resilient peptidoglycan (PG) mesh and
      other polymers surrounding cells. GpsB protein is conserved in low-GC Gram
      positive bacteria and is not essential in rod-shaped Bacillus subtilis, where it
      plays a role in shuttling penicillin-binding proteins (PBPs) between septal and
      side-wall sites of PG synthesis. In contrast, we report here that GpsB is
      essential in ellipsoid-shaped, ovococcal Streptococcus pneumoniae (pneumococcus),
      and depletion of GpsB leads to formation of elongated, enlarged cells containing
      unsegregated nucleoids and multiple, unconstricted rings of fluorescent
      vancomycin staining, and eventual lysis. These phenotypes are similar to those
      caused by selective inhibition of Pbp2x by methicillin that prevents septal PG
      synthesis. Dual-protein 2D and 3D-SIM (structured illumination)
      immunofluorescence microscopy (IFM) showed that GpsB and FtsZ have overlapping,
      but not identical, patterns of localization during cell division and that
      multiple, unconstricted rings of division proteins FtsZ, Pbp2x, Pbp1a and MreC
      are in elongated cells depleted of GpsB. These patterns suggest that GpsB, like
      Pbp2x, mediates septal ring closure. This first dual-protein 3D-SIM IFM analysis
      also revealed separate positioning of Pbp2x and Pbp1a in constricting septa,
      consistent with two separable PG synthesis machines. 

PMID- 24118411
TI  - Genome-wide analysis of DNA methylation changes induced by gestational arsenic
      exposure in liver tumors.
AB  - Inorganic arsenic is known to be a human carcinogen. Previous studies have
      reported that DNA methylation changes are involved in arsenic-induced
      carcinogenesis, therefore, DNA methylation changes that are specific to arsenic
      induced tumors would be useful to distinguish tumors induced by arsenic from
      tumors caused by other factors and to dissect arsenic carcinogenesis. Previous
      studies have shown that gestational arsenic exposure of C3H mice, which tend to
      spontaneously develop liver tumors, increases the incidence of tumors in male
      offspring. In this study we used the same experimental protocol as in those
      previous studies and searched for DNA regions where methylation status was
      specifically altered in the liver tumors of arsenic-exposed offspring by using
      methylated DNA immunoprecipitation-CpG island microarrays. The methylation levels
      of the DNA regions selected were measured by quantitative methylation-specific
      PCR and bisulfite sequencing. The results of this study clarified a number of
      regions where DNA methylation status was altered in the liver tumors in the C3H
      mice compared to normal liver tissues. Among such regions, we showed that a gene
      body region of the oncogene Fosb underwent alteration in DNA methylation by
      gestational arsenic exposure. We also showed that Fosb expression significantly
      increased corresponding to the DNA methylation level of the gene body in the
      arsenic-exposed group. These findings suggest that the DNA methylation status can
      be used to identify tumors increased by gestational arsenic exposure. 

PMID- 24118412
TI  - Tumoral presence of human cytomegalovirus is associated with shorter disease-free
      survival in elderly patients with colorectal cancer and higher levels of
      intratumoral interleukin-17.
AB  - Infectious diseases are closely related to cancer. Human cytomegalovirus (HCMV)
      has been implicated in the promotion of tumour growth, and is present in the
      tumour specimens of colorectal cancer (CRC). This study aimed to investigate
      whether tumoral presence of HCMV is associated with a different clinical outcome
      in elderly patients with CRC. We analysed archived tumour specimens from 95 CRC
      patients aged >=65 years. HCMV was detected by PCR. Clinical, pathological,
      disease-free and overall survival data were compared between patients with HCMV
      positive and HCMV-negative tumours. A quantitative RT-PCR array was used to
      evaluate the expression levels of cytokines genes of T-helper subpopulations in
      tumours. In the Kaplan-Meier analysis of the 81 patients who underwent curative
      surgery, 39 patients with HCMV-positive tumours had a lower disease-free survival
      rate (p 0.024). For patients with stage II or stage III tumours, tumoral HCMV
      status correlated with disease-free survival more closely than the traditional
      histopathological staging methods. In a multivariate Cox proportional hazard
      model, tumoral presence of HCMV independently predicted tumour recurrence in 5
      years (hazard ratio 4.42; 95% CI 1.54-12.69, p 0.006). The qRT-PCR analysis of
      ten stage II tumours showed that the gene expression levels of interleukin-17-the
      signature cytokine of T-helper 17 cells-and its receptor, interleukin-17 receptor
      C, were higher in the five HCMV-positive tumours. Our results suggest that the
      presence of HCMV in CRC is associated with poorer outcome in elderly patients.
      How the virus interacts with the tumour microenvironment should be further
      investigated.

PMID- 24118413
TI  - Clinical impact of the baseline donor-specific anti-human leukocyte antigen
      antibody measured by Luminex single antigen assay in living donor kidney
      transplant recipients after desensitization therapy.
AB  - The aim of this study is to investigate the clinical impact of donor-specific
      anti-HLA-antibody (HLA-DSA) baseline levels, measured using the Luminex single
      antigen assay (LSA), in living donor kidney transplantation (LDKT). Total 129
      cases of LDKT were divided into four groups according to baseline mean
      fluorescence intensity (MFI) HLA-DSA values: Strong (n = 6), >10,000; Moderate (n
      = 8), 5,000-10,000; Weak (n = 11), 1,000-5,000, Negative (n = 104), <1,000.
      Pretransplant desensitization (DSZ) was performed to decrease the MFI to weak or
      negative values before KT. Clinical outcomes in the four groups were compared.
      After DSZ, HLA-DSA decreased to weak or negative levels in all patients; Acute
      rejections developed more frequently in strong group [5/6 (83.3%)] compared with
      other three groups (P < 0.05), and especially acute antibody-mediated rejection
      (AAMR) developed almost exclusively in strong group [4/6 (66.7%)]. Strong HLA-DSA
      levels at baseline were more predictive of AAMR than either type of XM
      (complement-dependent lymphocytotoxicity or flow cytometry) in ROC analysis.
      Allograft function in this group showed significant deterioration during follow
      up compared with the other groups. In conclusion, strong HLA-DSA levels at
      baseline are associated with worse allograft outcome even after successful
      desensitization; therefore, strict monitoring and strong maintenance
      immunosuppression may be required in such patients.

PMID- 24118414
TI  - Work stress and cancer researchers: an exploration of the challenges, experiences
      and training needs of UK cancer researchers.
AB  - Work stress is a significant issue for many UK healthcare professionals, in
      particular those working in the field of oncology. However, there have been very
      few attempts to explore the challenges, experiences or training needs of
      researchers working in cancer research. In doing so, we will be better positioned
      to support and develop these researchers. Eighteen UK oncology researchers from a
      variety of backgrounds took part in a semi-structured interview. Interviews were
      transcribed and analysed using thematic analysis. The analysis identified two
      overarching themes: logistical research issues (workload, accessing/recruiting
      participants, finances) and sensitive research issues (emotional demands,
      professional boundaries, sensitivity around recruitment). One cross-cutting
      theme, supportive strategies (support and training, coping mechanisms), was seen
      to influence both logistical and sensitive research issues. While further
      research is needed to fully understand the causes and impact of work stress on
      cancer researchers, three specific issues were highlighted: emotional demands are
      relevant to quantitative and mixed methods researchers as well as those engaged
      in qualitative research; the researchers' background (experience; clinical/non
      clinical) was influential and an exploration of effective coping strategies is
      required; and there is a clear need for adequate support systems and training to
      be available, particularly for early career researchers. 

PMID- 24118415
TI  - A new KRT16 mutation associated with a phenotype of pachyonychia congenita.
AB  - Pachyonychia congenita is a rare, autosomal dominant genetic disease
      characterized by painful palmoplantar keratoderma and hypertrophic nail
      dystrophy. This disorder is caused by mutations in any one of five cytoskeletal
      keratin proteins, K6a, K6b, K6c, K16 and K17. Here, we describe a new p.Leu421Pro
      (c.1262T>C) mutation in the highly conserved helix termination motif of K16 in a
      large Spanish family. Bioinformatic analyses as well as previous descriptions in
      the literature of homologous mutations in other keratin-coding genes show that
      this mutation is probably causative of the disease. 

PMID- 24118417
TI  - Speciation in fishes.
AB  - The field of speciation has seen much renewed interest in the past few years,
      with theoretical and empirical advances that have moved it from a descriptive
      field to a predictive and testable one. The goal of this review is to provide a
      general background on research on speciation as it pertains to fishes. Three
      major components to the question are first discussed: the spatial, ecological and
      sexual factors that influence speciation mechanisms. We then move to the latest
      developments in the field of speciation genomics. Affordable and rapidly
      available, massively parallel sequencing data allow speciation studies to
      converge into a single comprehensive line of investigation, where the focus has
      shifted to the search for speciation genes and genomic islands of speciation. We
      argue that fish present a very diverse array of scenarios, making them an ideal
      model to study speciation processes. 

PMID- 24118416
TI  - Poor sleep in organ transplant recipients: self-reports and actigraphy.
AB  - Solid organ transplant recipients are at increased risk of poor sleep due to
      pharmacotherapy and co-morbidities, but sleep problems are often unrecognized and
      untreated. Study aims were to measure rates of occurrence, characteristics, and
      correlates of poor sleep in recipients. The Pittsburgh Sleep Quality Index (PSQI)
      and sleep parameters measured by wrist actigraphy were obtained at baseline from
      143 kidney, liver, heart, lung, or pancreas transplant recipients enrolled in a
      psychosocial intervention trial to improve symptoms and quality of life. Rates of
      poor sleep were determined using accepted clinical cutoffs; 41% (58 of 143) were
      poor sleepers (PSQI > 8) and 36% used sleep medications in the past month.
      Fifteen percent reported having obstructive sleep apnea (OSA) and 4% reported
      restless legs syndrome (RLS). Based on actigraphy (n = 73), 69% lacked sleep
      efficiency (SE), 32% took >30 min to fall asleep, 88% awakened during the night
      for more than 30 min, and 25% slept less than six h per night. Obesity and use of
      psychotropics or sleep medications, and pain were independent risk factors for
      poor objectively measured sleep. Poor sleep is an undertreated problem in
      transplantation. Screening for sleep problems and behavioral therapies with sleep
      hygiene instruction may benefit recipients.

PMID- 24118418
TI  - Blocking brain-derived neurotrophic factor inhibits injury-induced
      hyperexcitability of hippocampal CA3 neurons.
AB  - Brain trauma can disrupt synaptic connections, and this in turn can prompt axons
      to sprout and form new connections. If these new axonal connections are aberrant,
      hyperexcitability can result. It has been shown that ablating tropomyosin-related
      kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can
      reduce axonal sprouting after hippocampal injury. However, it is unknown whether
      inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given
      this, our purpose here was to determine whether pharmacologically blocking BDNF
      inhibits hyperexcitability after injury-induced axonal sprouting in the
      hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic
      hippocampal slice cultures. As reported by others, we observed a 50% reduction in
      axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after
      injury. Furthermore, lesioned cultures treated with TrkB-Fc were less
      hyperexcitable than lesioned untreated cultures. Using electrophysiology, we
      observed a two-fold decrease in the number of CA3 neurons that showed bursting
      responses after lesion with TrkB-Fc treatment, whereas we found no change in
      intrinsic neuronal firing properties. Finally, evoked field excitatory
      postsynaptic potential recordings indicated an increase in network activity
      within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment.
      Taken together, our results demonstrate that blocking BDNF attenuates injury
      induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been
      found in patients with post-traumatic epilepsy. Therefore, our data suggest that
      blocking the BDNF-TrkB signaling cascade shortly after injury may be a potential
      therapeutic target for the treatment of post-traumatic epilepsy. 

PMID- 24118419
TI  - Differences in the skin-surface laser Doppler signals between polycystic ovary
      syndrome and normal subjects.
AB  - BACKGROUND: Women with PCOS may present abnormal hemodynamic alterations and thus
      may develop vascular damage. This study performed LDF measurements on the skin
      surface around the leg to verify if beat-to-beat waveform and spectral analysis
      can help to discriminate the MBF characteristics between PCOS and healthy
      subjects. METHODS: ECG and LDF signals were obtained noninvasively in PCOS (n =
      16) and control (n = 8) subjects. Beat-to-beat waveform and spectral analysis was
      performed on the LDF signals to obtain the AD, FDT, FRT, and REC of five
      frequency bands. RESULTS: FRT was significantly larger, AD was significantly
      smaller, REC of the myogenic-related band was significantly smaller and REC of
      the heartbeat-related band was significantly larger in the PCOS than in the
      control subjects. CONCLUSION: This study is the first to reveal that time-domain
      waveform and spectral analysis performed on skin-surface LDF signals can be used
      to discriminate the differences in the MBF perfusion condition and the
      microcirculatory regulatory activities at local vascular beds between PCOS and
      healthy subjects. These findings may aid the noninvasive early detection of PCOS
      induced vascular damage.

PMID- 24118420
TI  - Contribution of the X chromosome to a marked reduction in lifespan in
      interspecies female hybrids of Drosophila simulans and D. mauritiana.
AB  - When two species come into contact and interbreed, the production of unfit
      hybrids can limit or prevent gene flow between the populations, thus maintaining
      each species' separate identity. The genetic basis of this hybrid dysfunction has
      recently begun to be elucidated, particularly for hybrid sterility and
      inviability. Although these dysfunctions can certainly act as a barrier to gene
      flow, other post-zygotic barriers may also play an important role in isolating
      species from one another. This study examines the genetic basis of the more
      subtle mechanism of species isolation via a marked reduction in lifespan of
      interspecies hybrid offspring. We found that females with homozygous X
      chromosomes in an otherwise interspecies hybrid background displayed a
      significant reduction in lifespan; this effect is not due to genetic background
      and appears to arise from complex genetic interactions. Separately, there is an
      additional severe reduction in lifespan for attached-X females when they have
      mated with males of either parental species, which is partly due to interspecific
      genetic interactions, but primarily due to a female's increased sensitivity to
      mating when bearing a Y chromosome or the attached-X chromosome construct. 

PMID- 24118421
TI  - The large-scale placebo-controlled beta-blocker studies in systolic heart failure
      revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with
      stratified subsets from MERIT-HF.
AB  - AIMS: The four pivotal beta-blocker trials in heart failure (HF) had different
      inclusion criteria, making comparison difficult without patient stratifying. The
      aim of this study was to compare, in similar patients, the effects of bisoprolol,
      metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol
      on (i) total mortality, (ii) all-cause mortality or hospitalization due to
      cardiovascular causes (time to first event), (iii) all-cause mortality or
      hospitalization because of HF and (iv) tolerability, defined as discontinuation
      of randomized treatment. METHODS: We compared stratified (s ) subsets in MERIT-HF
      with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and
      ejection fraction (EF) <= 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in
      patients with systolic HF in SENIORS-SHF (age >= 70 years and EF <= 35%).
      RESULTS: The annual mortality rates in the placebo and beta-blocker arms were:
      (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19
      46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction
      42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8%
      (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795),
      19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii)
      SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and
      MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53,
      P = 0.038). The effects on the other outcomes assessed were similar. Analyses
      indicated fewer discontinuations from randomized treatment on beta-blockers
      compared with placebo in COPERNICUS and the MERIT-HFs subsets. CONCLUSION: The
      efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are
      similar in patients with systolic HF, irrespective of NYHA class or ejection
      fraction. Nebivolol is less effective and not better tolerated.

PMID- 24118422
TI  - Assessment of left ventricular and atrial diastolic function using two
      dimensional (2D) strain imaging in patients with beta-thalassemia major.
AB  - BACKGROUND: beta-thalassemia major is a unique disease characterized by early
      severe diastolic dysfunction, due to iron myocardial deposition alone, while left
      ventricular systolic dysfunction and failure seem to be multifactorial in
      aitiology. OBJECTIVES: The purpose of this study was to investigate left
      ventricular diastolic dysfunction using a new echo index as speckle tracking in
      comparison with the conventional methods. MATERIAL AND METHODS: Eighty-eight
      consecutive patients (38 male, 50 female) aged 36 +/- 8.2 yr with beta
      thalassemia major and preserved LV ejection fraction (LVEF>55%) were studied.
      Patients were divided into two groups according to the E mitral/E mitral annulus
      ratio (E/E'): group A patients with E/E' ratio <=8 and group B patients with E/E'
      >8. Cutoff value of eight was used to separate patients with normal and abnormal
      diastolic function. All subjects were studied thoroughly by tissue Doppler
      echocardiography as also by 2D left ventricular and atrial strain imaging 2-4 d
      following blood transfusion. Blood samples were also taken for plasma BNP
      measurements at the same time. RESULTS: Left atrial volumes(LAV max, LAV min) as
      also left atrial index were significantly higher in patients with diastolic
      dysfunction compared with patients without diastolic dysfunction(LAV max: 57.6 +/
      19.4 vs. 71.3 +/- 22.9, P < 0.01,LAV min: 20.2 +/- 11.4 vs. 33.9 +/- 18, P <
      0.01, LAVI: 37.66 +/- 12.18 vs. 47.13 +/- 14.77, P < 0.01). Radial 2D strain (RS)
      and peak atrial 2D strain (AS) were significantly reduced in patients with
      suspected diastolic dysfunction compared with patients without diastolic
      dysfunction (RS: 43.48 +/- 13.92 vs. 35.58 +/- 11.32, P < 0.05; AS: 36.36 +/-
      8.45 vs. 29.85 +/- 9.25, P < 0.01). Using ROC analysis, peak atrial 2D strain at
      a cutoff of 41.1 cm/s was highly accurate (AUC: 0.66, P < 0.05 in ruling out
      diastolic dysfunction (E/E'<8) with a sensitivity of 90% and a specificity of
      81%. CONCLUSIONS: B-thalassemic major patients with preserved left ventricular
      systolic function had impaired left atrial function at the longitudinal axis and
      left ventricular function at the radial axis. The new echo markers have better
      prognostic value than the traditional echo indexes in detecting latent diastolic
      dysfunction in beta-thalassemia major, earlier than E/E' ratio.

PMID- 24118423
TI  - Plant hemoglobins may be maintained in functional form by reduced flavins in the
      nuclei, and confer differential tolerance to nitro-oxidative stress.
AB  - The heme of bacteria, plant and animal hemoglobins (Hbs) must be in the ferrous
      state to bind O(2) and other physiological ligands. Here we have characterized
      the full set of non-symbiotic (class 1 and 2) and 'truncated' (class 3) Hbs of
      Lotus japonicus. Class 1 Hbs are hexacoordinate, but class 2 and 3 Hbs are
      pentacoordinate. Three of the globins, Glb1-1, Glb2 and Glb3-1, are nodule
      enhanced proteins. The O(2) affinity of Glb1-1 (50 pm) was the highest known for
      any Hb, and the protein may function as an O(2) scavenger. The five globins were
      reduced by free flavins, which transfer electrons from NAD(P)H to the heme iron
      under aerobic and anaerobic conditions. Class 1 Hbs were reduced at very fast
      rates by FAD, class 2 Hbs at slower rates by both FMN and FAD, and class 3 Hbs at
      intermediate rates by FMN. The members of the three globin classes were
      immunolocalized predominantly in the nuclei. Flavins were quantified in legume
      nodules and nuclei, and their concentrations were sufficient to maintain Hbs in
      their functional state. All Hbs, except Glb1-1, were expressed in a
      flavohemoglobin-deficient yeast mutant and found to confer tolerance to oxidative
      stress induced by methyl viologen, copper or low temperature, indicating an anti
      oxidative role for the hemes. However, only Glb1-2 and Glb2 afforded protection
      against nitrosative stress induced by S-nitrosoglutathione. Because this compound
      is specifically involved in transnitrosylation reactions with thiol groups, our
      results suggest a contribution of the single cysteine residues of both proteins
      in the stress response.

PMID- 24118424
TI  - Safe ablation near the coronary ostium.

PMID- 24118425
TI  - Psoralen-narrowband UVB phototherapy for the treatment of vitiligo in comparison
      to narrowband UVB alone.
AB  - BACKGROUND: The potential of psoralen-narrowband ultraviolet B (NBUVB)
      photochemotherapy has been investigated in vitiligo. The present study aims to
      evaluate the efficacy of psoralen-NBUVB (P-NBUVB) vs. NBUVB in vitiligo. METHODS:
      In a randomized study, 45 Indian patients (age above 13 years) with vitiligo
      involving more than 5% body surface area were randomly allocated to receive
      either NBUVB or P-NBUVB treatment. Both groups received NBUVB exposure thrice
      weekly, with a total of 60 sessions. The extent of repigmentation achieved was
      calculated on the basis of Vitiligo Area Severity Index (VASI) scoring. RESULTS:
      Forty patients were available for analysis at the end of the study. The extent of
      repigmentation in the P-NBUVB group was statistically significantly greater in
      face and neck (P = 0.006, t-test) and hands (P = 0.007, t-test) in comparison
      with the NBUVB group (t-test). Percentage reduction in VASI scores was
      statistically significantly greater in the P-NBUVB group (29.2% vs. 21.7%, P =
      0.043, t-test). The response to P-NBUVB therapy started earlier than the response
      to NBUVB. After excluding sunlight as a confounding factor, treatment response
      was also significantly better in the P-NBUVB group (P = 0.005). CONCLUSION:
      Addition of psoralen increased the extent of repigmentation due to NBUVB therapy
      in vitiligo. Further studies are required to determine the long-term efficacy and
      safety of P-NBUVB.

PMID- 24118426
TI  - Cocaine-elicited imbalances in ventromedial prefrontal cortex Homer1 versus
      Homer2 expression: implications for relapse.
AB  - Withdrawal from a history of extended access to self-administered cocaine
      produces a time-dependent intensification of drug seeking, which might relate to
      a cocaine-induced imbalance in the relative expression of constitutively
      expressed Homer1 versus Homer2 isoforms within the ventromedial aspect of the
      prefrontal cortex (vmPFC). Thus, we employed immunoblotting to examine the
      relation between cue-reinforced lever pressing at 3- versus 30-day withdrawal
      from a 10-day history of extended access (6 hours/day) to intravenous cocaine
      (0.25 mg/infusion) or saline (Sal6h), and the expression of Homer1b/c and
      Homer2a/b within the vmPFC versus the more dorsomedial aspect of this structure
      (dmPFC). Behavioral studies employed adeno-associated virus (AAV) vectors to
      reverse cocaine-elicited changes in the relative expression of Homer1 versus
      Homer2 isoforms and tested animals for cocaine prime-, and cue-induced responding
      following extinction training. Cocaine self-administration elevated both
      Homer1b/c and Homer2a/b levels within the vmPFC at 3-day withdrawal, and the rise
      in Homer2a/b persisted for at least 30 days. dmPFC Homer levels did not change as
      a function of self-administration history. Reversing the relative increase in
      Homer2 versus Homer1 expression via Homer1c overexpression or Homer2b knockdown
      failed to influence cue-reinforced lever pressing when animals were tested in a
      drug-free state, but both AAV treatments prevented cocaine-primed reinstatement
      of lever-pressing behavior. These data suggest that a cocaine-elicited imbalance
      in the relative expression of constitutively expressed Homer2 versus Homer1
      within the vmPFC is necessary for the capacity of cocaine to reinstate drug
      seeking behavior, posing drug-induced changes in vmPFC Homer expression as a
      molecular trigger contributing to drug-elicited relapse. 

PMID- 24118427
TI  - Coexistence of amyotrophic lateral sclerosis with neuro-Behcet's disease
      presenting as a longitudinally extensive spinal cord lesion: clinicopathologic
      features of an autopsied patient.
AB  - We report the clinical and autopsy features of a 65-year-old Japanese man who
      clinically exhibited overlap of both neuro-Behcet's disease (NBD) and amyotrophic
      lateral sclerosis (ALS). The patient had a HLA-B51 serotype, a recent history of
      uveitis and had suffered paraparesis, sensory and autonomic disturbance, frontal
      signs and tremor. A brain and spine MRI study revealed a longitudinally extensive
      thoracic cord (Th) lesion, but no apparent intracranial abnormalities. The lesion
      extended ventrally from Th4 to Th9, exhibiting low intensity on T1-weighted
      images, high intensity on T2-weighted and fluid-attenuated inversion recovery
      images and gadolinium enhancement. The patient's upper and lower motor neuron
      signs and sensory disturbance worsened and he died 16 months after admission. At
      autopsy, the spinal cord and brain exhibited characteristic histopathological
      features of both NBD and ALS, including chronic destruction of the ventral
      thoracic white and gray matter, perivascular lymphocytic infiltration,
      binucleated neurons, lower and upper motor neuron degeneration, Bunina bodies and
      skein-like inclusions. Although incidental coexistence of these rare disorders
      could occur in an individual, this case raises the possibility of a
      pathomechanistic association between NBD and ALS. 

PMID- 24118428
TI  - Mindfulness-based cancer stress management: impact of a mindfulness-based
      programme on psychological distress and quality of life.
AB  - Within the area of cancer care, mindfulness-based therapeutic interventions have
      been found to be efficacious in reducing psychological distress related to a
      cancer diagnosis; however, the impact of mindfulness-based interventions on
      quality of life is unclear. This study explores the impact of a Mindfulness-Based
      Cancer Stress Management programme on psychological distress and quality of life.
      Research methodology included a single-group quasi-experimental study of 26
      participants experiencing distress related to a cancer diagnosis, including
      carers, who completed an MBCSM programme and all assessments. Participants
      completed the Functional Assessment of Cancer Therapy - General version 4 (FACT
      G) and its associated spirituality index (FACIT-Sp-Ex), Hospital Anxiety and
      Depression Scale (HADS), Freiburg Mindfulness Inventory (FMI), and the Distress
      Thermometer at baseline, post-intervention, and three months after programme
      completion. Significant improvements were observed on all measures (ranges: P <=
      0.001 to 0.008, r = -0.53 to -0.79) following the intervention, which were
      maintained at 3-month follow-up. Mindfulness was significantly correlated with
      all main outcome measures at post-intervention (range: r = -0.41 to 0.67) and 3
      month follow-up (range: r = -0.49 to 0.73), providing evidence for the internal
      validity of the study. Our findings indicate that the MBCSM programme is
      effective in reducing psychological distress and improving quality of life,
      including spiritual well-being. 

PMID- 24118429
TI  - Early bone apposition to hydrophilic and hydrophobic titanium implant surfaces: a
      histologic and histomorphometric study in minipigs.
AB  - OBJECTIVE: The first objective of this pilot study was to evaluate the impact of
      the hydrophilicity on the early phases of osseointegration. The second objective
      was to compare two hydrophilic implant surfaces with different geometries,
      surface roughness, and technologies achieving hydrophilicity. MATERIAL AND
      METHODS: Twelve weeks after extraction, all four quadrants of nine minipigs
      received three dental implants, alternating between hydrophilic microrough
      surfaces (INICELL and SLActive) and a conventional hydrophobic microrough
      surface. After 5, 10, and 15 days of submerged healing, ground sections were
      prepared and subjected to histologic and histomorphometric analysis. RESULTS: The
      histologic analysis revealed a similar healing pattern among the hydrophilic and
      hydrophobic implant surfaces, with extensive bone formation occurring between day
      5 and day 10. With BIC values of greater than 50% after 10 days, all examined
      surfaces indicated favorable osseointegration at this very early point in
      healing. At day 15, the mean new bone-to-implant contact (newBIC) of one
      hydrophilic surface (INICELL; 55.8 +/- 14.4%) was slightly greater than that of
      the hydrophobic microrough surface (40.6 +/- 20.2%). At day 10 and day 15, an
      overall of 21% of the implants had to be excluded from analysis due to
      inflammations primarily caused by surgical complications. CONCLUSION: Substantial
      bone apposition occurs between day 5 and day 10. The data suggest that the
      hydrophilic surface can provoke a slight tendency toward increased bone
      apposition in minipigs after 15 days. A direct comparison of two hydrophilic
      surfaces with varying geometries is of limited relevance.

PMID- 24118430
TI  - Surgical outcomes and quality of life post-synthetic mesh-augmented repair for
      pelvic organ prolapse in the Chinese population.
AB  - AIM: To investigate the surgical outcomes, urinary incontinence and quality of
      life (QOL) of patients with pelvic organ prolapse after synthetic mesh-augmented
      repair in the Chinese population. METHOD: This is a retrospective study of women
      who underwent synthetic mesh-augmented repair. Surgical outcomes were
      investigated by recurrence rate of prolapse and Organ Prolapse Quantification,
      and QOL by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and Pelvic Floor Distress
      Inventory-20 (PFDI-20). The sex life quality was evaluated by Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire-31 (PISQ-31). RESULTS: Eighty
      three patients completed the entire study. Anatomical success was 90.36%. Of
      patients with preoperative stress urinary incontinence, 91.89% claimed that the
      incontinence symptoms were completely relieved. The 6-month PFDI-20 and PFIQ-7
      scores were significantly decreased, indicating that improved QOL occurs.
      However, the PISQ-31 showed no significant difference between preoperative and
      postoperative data in sex life quality. CONCLUSION: The synthetic polypropylene
      mesh is effective in treating POP and may improve QOL with no significant
      difference in the sexual life postoperatively. De novo stress urinary
      incontinence may occur after synthetic mesh-augmented repair.

PMID- 24118431
TI  - Epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli in
      Sweden 2007-2011.
AB  - Extended-spectrum beta-lactamase (ESBL) -producing Enterobacteriaceae have been
      notifiable according to the Swedish Communicable Disease Act since 2007. A major
      increase in the number of cases has been observed, with 2099 cases in 2007 and
      7225 cases in 2012. The majority of the isolates are Escherichia coli.
      Additionally, Swedish data on the prevalence of ESBL-producing invasive isolates
      of E. coli are available through EARS-Net, and through biannual point prevalence
      studies, where molecular characterization of isolates from the entire country is
      carried out. This paper describes major trends in the Swedish epidemiology of
      ESBL-producing E. coli in the period 2007-2012. Isolates from the point
      prevalence studies were subjected to antimicrobial susceptibility testing, ESBL
      genotyping, pulsed-field gel electrophoresis, multi-locus sequence typing and
      phylogenetic grouping with PCR. The distribution of sequence types, resistance
      genes and susceptibility levels were all stable over the three study periods. The
      dominating resistance gene conferring ESBL was blaCTX -M-15 , found in 54-58% of
      the isolates. ST131 represented 34-38% of the isolates. Other major sequence
      types were ST38, ST69, ST405, ST617 and ST648, each representing 2-6% of the
      isolates. Phylogenetic group B2 was the most common, and was observed in 41-47%
      of the isolates. However, among ST131 isolates the B2 phylogenetic group
      represented 90-98% of the isolates. The most important epidemiological difference
      seen over time was that the median age of infected women decreased from 62 to 52
      years (p <0.0001) and infected men from 67 to 64 years. A potential explanation
      might be the shift towards a higher proportion of community-acquired infections
      in individuals lacking comorbidities.

PMID- 24118432
TI  - Determinants of moderate-to-severe anaemia among women of reproductive age in
      Tanzania: analysis of data from the 2010 Tanzania Demographic and Health Survey.
AB  - OBJECTIVE: To identify determinants of moderate-to-severe anaemia among women of
      reproductive age in Tanzania. METHODS: We included participants from the 2010
      Tanzania Demographic and Health Survey, which collected data on socio-demographic
      and maternal health and determined haemoglobin levels from blood samples. We
      performed logistic regression to calculate adjusted odds ratios for associations
      between socio-demographic, contextual, reproductive and lifestyle factors, and
      moderate-to-severe anaemia and investigated interactions between certain risk
      factors. RESULTS: Of 9477 women, 20.1% were anaemic. Pregnancy was significantly
      associated with anaemia (adjusted OR 1.75, 95% CI 1.43-2.15), but the effect
      varied significantly by urban/rural residence, wealth and education. The effect
      of pregnancy was stronger in women without education and those who were in lower
      wealth groups, with significant interactions observed for each of these factors.
      Education was associated with a lower anaemia risk, particularly in the poorest
      group (OR 0.58, 95% CI 0.43-0.80), and in pregnant women. The risk of anaemia
      fell with rising iron supplementation coverage. Lack of toilet facilities
      increased anaemia risk (OR 1.26, 95% CI 1.00-1.60), whereas using hormonal
      contraception reduced it. There was no association with age, urban/rural
      residence, wealth or type of cooking fuel in adjusted analysis. CONCLUSION:
      Pregnant women in Tanzania are particularly at risk of moderate-to-severe
      anaemia, with the effect modified by urban/rural residence, education and wealth.
      Prevention interventions should target women with lower education or without
      proper sanitation facilities, and women who are pregnant, particularly if they
      are uneducated or in lower wealth groups.

PMID- 24118433
TI  - Ultrasound in-depth characterization and staging of hidradenitis suppurativa.
AB  - BACKGROUND: The clinical diagnosis of fistulous tracts and recurrent fluid
      collections in hidradenitis suppurativa (HS) may be complex. Information on
      subclinical involvement and grading of severity may improve management.
      OBJECTIVE: To study HS lesions and evaluate the relevance of adding ultrasound
      (US) to the clinical examination. METHODS AND MATERIALS: We reviewed the
      sonograms of consecutive patients with HS from January 1, 2010 to May 31, 2012.
      The abnormalities observed in the US examinations were organized, classified, and
      integrated into a clinical-sonographic scoring system (SOS-HS), to stage the
      disease. RESULTS: Thirty-four patients with HS with a total of 142 lesional areas
      were evaluated. US findings included subclinical fluid collections in 76.4% of
      the patients, fistulous tracts in 29.4%, dermal pseudocysts in 70.6%, and
      widening of the hair follicles in 100%. Concordance with the clinical HS scoring
      performed by dermatologists showed a significant fair agreement (k = 0.30; p <
      .001); concordance of SOS-HS with clinical scores was acceptable but
      significantly lower (k = 0.27; p = .02) because clinical scores consistently
      underestimated disease stage and severity. CONCLUSION: US examination of HS
      lesions provides anatomic information that is clinically unavailable. HS is
      possible to stage sonographically.

PMID- 24118434
TI  - Interaction of disulfiram with antiretroviral medications: efavirenz increases
      while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism.
AB  - BACKGROUND AND OBJECTIVES: Alcohol abuse complicates treatment of HIV disease and
      is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram
      (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders
      possibly related to concerns about drug interactions between antiretroviral (ARV)
      medications and DIS. METHOD: This pharmacokinetics study (n=40) examined the
      effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the
      effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase
      (ALDH) activity which mediates the DIS-alcohol reaction. RESULTS: EFV
      administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate
      (DIS carbamate), a metabolite of DIS (p=.001) and a precursor to the metabolite
      responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide
      (DETC-MeSO). EFV was associated with increased DIS inhibition of ALDH activity
      relative to DIS alone administration possibly as a result of EFV-associated
      induction of CYP 3A4 which metabolizes the carbamate to DETC-MeSO (which inhibits
      ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH
      activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration
      had no significant effect on any ARV studied. DISCUSSION/CONCLUSIONS: ATV may
      render DIS ineffective in treatment of alcoholism. FUTURE DIRECTIONS: DIS is
      infrequently utilized in HIV-infected individuals due to concerns about adverse
      interactions and side effects. Findings from this study indicate that, with
      ongoing clinical monitoring, DIS should be reconsidered given its potential
      efficacy for alcohol and potentially, cocaine use disorders, that may occur in
      this population.

PMID- 24118436
TI  - Knowledge expectations of surgical orthopaedic patients: a European survey.
AB  - Ageing population entails a growing international problem of osteoarthritis. Best
      practices for education of these patients are lacking. This study focused on
      empowering education in Northern (Finland, Iceland, Lithuania and Sweden) and
      Southern Europe (Cyprus, Greece and Spain). The aim was to analyse associations
      between expected knowledge and background factors. The data were collected from
      European arthroplasty patients with the Knowledge Expectations of hospital
      patients- scale, (KE(hp) - scale), including bio-physiological, functional,
      experiential, ethical, social and financial dimensions. Patients had essential
      bio-physiological and functional knowledge expectations. Women expected more than
      men, employed less than retired, unemployed or who worked at home. Generally,
      patients in Northern countries expected more than in Southern countries. However,
      highest expectations were found in Sweden and Greece, lowest in Spain and Cyprus.
      There are differences in knowledge expectations based on patients' backgrounds.
      Development of common standards in European patient education needs further
      research.

PMID- 24118435
TI  - Tracing horizontal Wolbachia movements among bees (Anthophila): a combined
      approach using multilocus sequence typing data and host phylogeny.
AB  - The endosymbiotic bacterium Wolbachia enhances its spread via vertical
      transmission by generating reproductive effects in its hosts, most notably
      cytoplasmic incompatibility (CI). Additionally, frequent interspecific horizontal
      transfer is evident from a lack of phylogenetic congruence between Wolbachia and
      its hosts. The mechanisms of this lateral transfer are largely unclear. To
      identify potential pathways of Wolbachia movements, we performed multilocus
      sequence typing of Wolbachia strains from bees (Anthophila). Using a host
      phylogeny and ecological data, we tested various models of horizontal
      endosymbiont transmission. In general, Wolbachia strains seem to be randomly
      distributed among bee hosts. Kleptoparasite-host associations among bees as well
      as other ecological links could not be supported as sole basis for the spread of
      Wolbachia. However, cophylogenetic analyses and divergence time estimations
      suggest that Wolbachia may persist within a host lineage over considerable
      timescales and that strictly vertical transmission and subsequent random loss of
      infections across lineages may have had a greater impact on Wolbachia strain
      distribution than previously estimated. Although general conclusions about
      Wolbachia movements among arthropod hosts cannot be made, we present a framework
      by which precise assumptions about shared evolutionary histories of Wolbachia and
      a host taxon can be modelled and tested. 

PMID- 24118437
TI  - Behind the (impedance) baseline in children.
AB  - Impedance baseline is a new parameter recently related to esophageal integrity.
      The aim of this study was to assess the effect of different factors on impedance
      baseline in pediatric patients. We analyzed the impedance baseline of 800
      children with symptoms of gastroesophageal reflux. Mean impedance baseline was
      automatically calculated throughout 24-hour tracings. The presence of different
      age groups and of esophagitis was evaluated. Unpaired t-test, Spearman rank
      correlation, polynomial, and regression plot were used for statistical analysis.
      Age-related percentile curves were created. We considered a P-value<0.05 as
      statistically significant. Impedance baseline was significantly (P<0.001) lower
      in younger compared to older children up to 48 months. The mean increase of
      baseline per month was much higher in the first 36 months of life (47.5 vs. 2.9
      Ohm in Channel 1 and 29.9 vs. 2.3 Ohm in Channel 6, respectively) than in older
      ages. Patients with esophagitis showed significantly decreased impedance baseline
      (P<0.05). Infants (especially in the first months of life) and young children
      present a significantly lower impedance baseline compared to older children both
      in proximal and distal esophagus. The presence of esophagitis may also determine
      a decreased impedance baseline regardless of the age of the patients.

PMID- 24118438
TI  - Electronic fetal heart rate monitoring in five fetuses with Ebstein's anomaly.
AB  - AIM: It is not clear whether fetuses with Ebstein's anomaly are likely to show
      abnormalities on electronic fetal heart rate (FHR) monitoring during labor.
      METHODS: We performed retrospective analysis of FHR monitoring results obtained
      between 2.5 and 0.5 h prior to delivery in all of five fetuses prenatally
      diagnosed as having Ebstein's anomaly and born at our institution during the
      period between March 2005 and July 2011. All five mothers attempted to give birth
      vaginally. The results of FHR monitoring in 100 consecutive women with otherwise
      healthy singletons who attempted vaginal delivery were included as controls.
      RESULTS: The absence of FHR acceleration (4/5 [80%]), decreased baseline FHR
      variability (3/5 [60%]) and late deceleration (4/5 [80%]) were seen significantly
      more often in the five fetuses with Ebstein's anomaly than the 100 fetuses born
      to control women (6.0%, 6.0%, and 10%, respectively). CONCLUSION: Fetuses with
      Ebstein's anomaly during labor were likely to exhibit absent acceleration,
      decreased baseline FHR variability and late deceleration compared to infants
      without cardiac structural anomalies.

PMID- 24118439
TI  - Safety of brachial arteriogram using a 3-French dilator to evaluate nonmaturing
      arteriovenous fistulae.
AB  - Nonmaturing arteriovenous fistula remains a hurdle in improving the fistula rate
      in the hemodialysis population. Timely referral can assist in salvaging fistula
      with endovascular interventions. Pathology at the inflow segment is frequently
      encountered as a primary reason for maturation failure. Conventional retrograde
      angiography can result in poor delineation of the inflow segment and may not be
      an ideal method for evaluating nonmaturing fistulae. Moreover, the risk of
      vascular rupture and overzealous diagnosis of accessory veins often result in
      additional unnecessary therapeutic interventions. Alternatively, a direct
      brachial arteriogram can provide complete anatomic delineation to perform
      appropriate endovascular interventions. 

PMID- 24118441
TI  - Influencing factors on the functional level of haemophilic patients assessed by
      FISH.
AB  - Joint destruction in early adulthood brings the patients to the orthopaedic
      clinics. If a haemophilic patient becomes disabled, it shows a number of factors
      such as timely diagnosis, availability of appropriate treatment depending on the
      country, access and affordability to treatments and equally importantly the
      responsibility of the patient in managing self care by remaining compliant by
      prescribed treatment regimen. We assessed the functional level by functional
      independence score in haemophilia (FISH). Overall, 104 patients with haemophilia
      A and 29 with haemophilia B were evaluated. We assessed the function of the
      patients by FISH. We divided the sum scores into weak (FISH score 8-16), moderate
      (17-24), and good (25-32). For evaluating the level of functional deficit in a 2
      * 2 table, we categorized the weak and moderate levels into Disordered Group and
      the good level into Not-Disordered Group. The average age was 26.9 +/- 14.24.
      Each 1 year increase in age can increase 1.07 fold the possibility of being
      placed in Disordered Function Group. Severe haemophilia can increase 7.34 fold,
      presence of inhibitor can increase 9.75 fold and home self-care increases 3.89
      fold the possibility of being placed in Disordered Function Group. To decrease
      the burden of the cost on patient, family and the government, education plays the
      most important role. We suggest that we send a trained team of physician and
      nurses to the deprived villages and cities instead of waiting for the patient to
      refer to our Care Center.

PMID- 24118440
TI  - Papillomavirus-associated multicentric squamous cell carcinoma in situ in a cat:
      an unusually extensive and progressive case with subsequent metastasis.
AB  - BACKGROUND: Multicentric squamous cell carcinoma in situ (MSCCIS) is an uncommon
      cutaneous disease of middle-aged to older cats, with some cases being linked to
      papillomavirus infection. The disease course is usually benign. Initial eruption
      of multifocal, pigmented, hyperkeratotic plaques is typical, with gradual
      progression to thickly crusted ulcerative lesions. ANIMAL: A 5-year-old male
      neutered Devon rex cat in apparent good health was initially presented with a 16
      month history of over 40 nonpruritic dorsally distributed hyperpigmented patches.
      Lesions progressed gradually over 2 years to larger, more pigmented, crusted
      plaques and ulcerated nodules. At 7 years of age the cat developed neurological
      signs and systemic illness and was euthanized. METHODS AND RESULTS: Initial skin
      histopathology revealed discrete regions of epidermal and follicular epithelial
      hyperplasia, with moderate numbers of apoptotic keratinocytes, and mild focal
      epithelial dysplasia. A diagnosis of erythema multiforme was considered; feline
      herpesvirus-1 immunohistochemistry was negative. Repeat histopathology 22 months
      after initial presentation confirmed MSCCIS with foci of invasive squamous cell
      carcinoma (SCC). Postmortem examination 1 month later revealed SCC within the
      thoracic wall, lungs and vessels of the thoracic spinal cord and heart base,
      presumed to be metastases from skin lesions. Fluorescent in situ hybridization of
      initial and later histopathology samples was positive for Felis domesticus
      papillomavirus type 2. Immunoreactivity of p16 was prominent within early and
      late cutaneous lesions and internal SCCs. CONCLUSIONS: This case represents an
      unusual presentation of papillomavirus-associated MSCCIS with extensive lesions,
      atypical initial histopathology and progression to SCC with distant metastases.

PMID- 24118442
TI  - Relationship between the interleukin-6-174 gene and mannose-binding lectin codon
      54 gene polymorphisms and condyloma acuminatum.
AB  - BACKGROUND: Several genes encoding different Th1 and Th2 cytokines may play
      crucial roles in host susceptibility to Condyloma acuminatum (CA). Mannose
      binding lectin (MBL) is a serum lectin that mediates complement activation, and
      it is a member of innate immune system. MBL gene polymorphisms are considered to
      be associated with several infectious diseases. OBJECTIVE: In this study, we
      investigated the association between cytokines and MBL gene polymorphisms with
      CA. METHODS: Forty patients with CA and 40 healthy controls were enrolled in this
      study. These patients had not responded to at least a therapy modality and all
      patients had recurrent lesions. Polymorphism of cytokine [Th1 cytokines; tumour
      necrosis factor-alpha and interferon (IFN)-gamma, Th2 cytokine; IL-6, T
      regulatory/suppressor cytokines; IL-10 and transforming growth factor-beta] genes
      studies were performed by Polymerase chain reaction sequence-specific primers
      method and MBL genotyping were studied by PCR-restriction fragment length
      polymorphism method. RESULTS: With the aid of agglomerative hierarchical cluster
      analysis, we categorized subjects into two main clusters (cluster 1; formed by
      the majority of patients with CA, cluster 2; formed by the majority of healthy
      controls), which were found to have significantly different distributions of IL-6
      and MBL genotypes. Frequencies of IL-6 (-174) G/G (P < 0.001) and MBL AA (P <
      0.001) polymorphisms were significantly greater in the cluster 1. In contrast,
      significantly lower frequencies of the IL-6 G/C (P = 0.046) genotype and MBL AB
      (P < 0.001) genotype were observed in cluster 1. CONCLUSION: These results
      suggest that the IL-6 G/G and MBL AA gene polymorphisms are potential risk
      factors and that the IL-6 G/C and MBL AB polymorphisms are a protective factor
      for occurrence and recurrence of CA.

PMID- 24118443
TI  - The lipid II flippase RodA determines morphology and growth in Corynebacterium
      glutamicum.
AB  - Lipid II flippases play an essential role in cell growth and the maintenance of
      cell shape in many rod-shaped bacteria. The putative lipid II flippase RodA is an
      integral membrane protein and member of the SEDS (shape, elongation, division and
      sporulation) protein family. In contrast to its homologues in Escherichia coli
      and Bacillus subtilis little is known about the role of RodA in actinobacteria.
      In this study, we describe the localization and function of RodA in
      Corynebacterium glutamicum, a rod-shaped, apically growing actinobacterium. RodA
      GFP localizes exclusively at the cell poles. Surprisingly, time-lapse microscopy
      revealed that apical cell growth is sustained in a rodA deletion strain. However,
      growth rates and antibiotic susceptibility are altered. In the absence of RodA,
      it appears that apical growth is driven by lateral diffusion of lipid II that is
      likely flipped by the septal flippase, FtsW. Furthermore, we applied a previously
      described synthetic in vivo system in combination with FRET to identify an
      interaction between C. glutamicum RodA and the polar growth organizing protein
      DivIVA.

PMID- 24118444
TI  - Calcium homeostasis and sensitization in pulmonary arterial smooth muscle.
AB  - The pulmonary circulation is a low-pressure, low-resistance vascular bed with
      little to no resting tone under normal conditions. An increase in the [Ca(2+) ]i
      in PASMCs is an important determinant of contraction, migration, and
      proliferation. Both Ca(2+) influx through plasma membrane Ca(2+) channels and
      Ca(2+) release from the SR contribute to a rise in [Ca(2+) ]i . Additionally
      important in the pulmonary circulation are several kinase-mediated signaling
      pathways that act to increase the sensitivity of the contractile apparatus to
      [Ca(2+) ]i . Similarly, cytoskeletal processes resulting in dynamic remodeling of
      the actin cytoskeleton can further contribute to contractility in the pulmonary
      circulation. In addition to endocrine, paracrine, and autocrine factors, alveolar
      hypoxia is an important stimulus for pulmonary vasoconstriction. However,
      prolonged hypoxia is a critical pathological stimulus associated with the
      development of pulmonary hypertension and cor pulmonale. In this review, we will
      discuss recent advances in our understanding of how Ca(2+) homeostasis and
      sensitization regulate PASMC contractility under both physiological and
      pathophysiological conditions. 

PMID- 24118445
TI  - Wise decisions on renal replacement therapy require knowledgeable patients and
      good self-report knowledge scales*.

PMID- 24118446
TI  - Amurensin G enhances the susceptibility to tumor necrosis factor-related
      apoptosis-inducing ligand-mediated cytotoxicity of cancer stem-like cells of HCT
      15 cells.
AB  - Cancer stem cells (CSCs) are resistant to radiotherapy and chemotherapy and play
      a significant role in cancer recurrence. Design of better treatment strategies
      that can eliminate or otherwise control CSC populations in tumors is necessary.
      In this study, the sensitivity to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced cytotoxicity and the effect of amurensin G, a
      novel sirtuin 1 (SIRT1) inhibitor, were examined using the CSC-enriched fraction
      of HCT-15 human colon cancer cells. Cancer stem cell-enriched HCT-15 colony cells
      were paradoxically less sensitive to doxorubicin, and more sensitive to TRAIL
      induced cytotoxicity, than their parental cells. Also, CD44(+) HCT-15 cells were
      more susceptible to TRAIL-mediated cytotoxicity than CD44(-) HCT-15 cells,
      possibly due to increased levels of death receptors DR4 and DR5 as well as c-Myc,
      and decreased levels of c-FLIPL /S in CD44(+) cells compared with CD44(-) HCT-15
      cells. The combination effect of amurensin G on TRAIL-mediated cytotoxicity was
      much more apparent in CD44(+) cells than in CD44(-) HCT-15 cells, and this was
      associated with more prominent downregulation of c-FLIP(L/S) in CD44(+) cells
      than in CD44(-) HCT-15 cells. These results indicate that HCT-15 colony or
      CD44(+) cells, which may have CSC properties, are more sensitive to TRAIL than
      parental or CD44(-) HCT-15 cells. Amurensin G may be effective in eliminating
      colon CSCs and be applicable to potentiate the sensitivity of colon CSCs to
      TRAIL.

PMID- 24118447
TI  - Corticosterone regulates multiple colour traits in Lacerta [Zootoca] vivipara
      males.
AB  - Ornamental colours usually evolve as honest signals of quality, which is
      supported by the fact that they frequently depend on individual condition. It has
      generally been suggested that some, but not all types of ornamental colours are
      condition dependent, indicating that different evolutionary mechanisms underlie
      the evolution of multiple types of ornamental colours even when these are
      exhibited by the same species. Stress hormones, which negatively affect
      condition, have been shown to affect colour traits based on different pigments
      and structures, suggesting that they mediate condition dependence of multiple
      ornament types both among and within individuals. However, studies investigating
      effects of stress hormones on different ornament types within individuals are
      lacking, and thus, evidence for this hypothesis is scant. Here, we investigated
      whether corticosterone mediates condition dependence of multiple ornaments by
      manipulating corticosterone levels and body condition (via food availability)
      using a two-factorial design and by assessing their effect on multiple colour
      traits in male common lizards. Corticosterone negatively affected ventral melanin
      and carotenoid-based coloration, whereas food availability did not affect
      coloration, despite its significant effect on body condition. The corticosterone
      effect on melanin- and carotenoid-based coloration demonstrates the condition
      dependence of both ornaments. Moreover, corticosterone affected ventral
      coloration and had no effect on the nonsexually selected dorsal coloration,
      showing specific effects of corticosterone on ornamental ventral colours. This
      suggests that corticosterone simultaneously mediates condition dependence of
      multiple colour traits and that it therefore accounts for covariation among them,
      which may influence their evolution via correlational selection. 

PMID- 24118448
TI  - Molecular assessment of heterotrophy and prey digestion in zooxanthellate
      cnidarians.
AB  - Zooxanthellate cnidarians are trophically complex, relying on both autotrophy and
      heterotrophy. Although several aspects of heterotrophy have been studied in these
      organisms, information linking prey capture with digestion is still missing. We
      used prey-specific PCR-based tools to assess feeding and prey digestion of two
      zooxanthellate cnidarians - the tropical sea anemone Aiptasia sp. and the
      scleractinian coral Oculina arbuscula. Prey DNA disappeared rapidly for the
      initial 1-3 days, whereas complete digestion of prey DNA required up to 10 days
      in O. arbuscula and 5 or 6 days in Aiptasia sp. depending on prey species. These
      digestion times are considerably longer than previously reported from microscopy
      based examination of zooxanthellate cnidarians and prey DNA breakdown in other
      marine invertebrates, but similar to prey DNA breakdown reported from terrestrial
      invertebrates such as heteroptera and spiders. Deprivation of external prey
      induced increased digestion rates during the first days after feeding in O.
      arbuscula, but after 6 days of digestion, there were no differences in the
      remaining prey levels in fed and unfed corals. This study indicates that prey
      digestion by symbiotic corals may be slower than previously reported and varies
      with the type of prey, the cnidarian species and its feeding history. These
      observations have important implications for bioenergetic and trophodynamic
      studies on zooxanthellate cnidarians.

PMID- 24118449
TI  - Recent progress in migraine pathophysiology: role of cortical spreading
      depression and magnetic resonance imaging.
AB  - Migraine is characterised by debilitating pain, which affects the quality of life
      in affected patients in both the western and the eastern worlds. The purpose of
      this article is to give a detailed outline of the pathophysiology of migraine
      pain, which is one of the most confounding pathologies among pain disorders in
      clinical conditions. We critically evaluate the scientific basis of various
      theories concerning migraine pathophysiology, and draw insights from brain
      imaging approaches that have unraveled the prevalence of cortical spreading
      depression (CSD) in migraine. The findings supporting the role of CSD as a
      physiological substrate in clinical pain are discussed. We also give an
      exhaustive overview of brain imaging approaches that have been employed to solve
      the genesis of migraine pain, and its possible links to the brainstem, the
      neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic
      hypersensitivity). Furthermore, a roadmap is proposed to provide a better
      understanding of pain pathophysiology in migraine, to enable the development of
      strategies using leads from brain imaging studies for the identification of early
      biomarkers, efficient prognosis, and treatment planning, which eventually may
      help in alleviating some of the devastating impact of pain morbidity in patients
      afflicted with migraine. 

PMID- 24118450
TI  - A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs.
      the reference formulation in subpopulations of kidney transplant patients.
AB  - An exploratory, post hoc analysis was performed using data from a prospective,
      multicenter, open-label, randomized, two-period (14 d per period), two-sequence,
      crossover, steady-state pharmacokinetic study comparing generic tacrolimus
      (Sandoz) vs. reference tacrolimus in stable renal transplant patients receiving
      their pre-study twice-daily dose. Pharmacokinetic parameters were compared in 68
      patients according to gender, African American ethnicity, the presence or absence
      of diabetes, and use of steroids. The ratios of tacrolimus AUC0-12 h , Cmax , and
      C12 with generic vs. reference tacrolimus were calculated using the geometric
      mean (GM) of dose-normalized values at days 14 and 28. Mean (SD) tacrolimus dose
      at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose
      normalized AUC0-12 h , C12 , Cmax, or tmax between the generic and reference
      preparations within subpopulations. The 90% confidence intervals (CI) for the
      ratios of dose-normalized AUC0-12 h and C12 with generic vs. reference tacrolimus
      were within 80-125% for all subpopulations, as were 90% CIs for Cmax other than
      for females, African Americans, and non-diabetics, which is not unexpected given
      the wide variability of tacrolimus Cmax and the small subpopulation sizes. These
      exploratory results suggest that this generic tacrolimus preparation would be
      expected to offer comparable bioavailability to the reference drug in these
      patient subpopulations.

PMID- 24118451
TI  - Ceruloplasmin and atrial fibrillation: evidence of causality from a population
      based Mendelian randomization study.
AB  - OBJECTIVES: Inflammatory diseases and inflammatory markers secreted by the liver,
      including C-reactive protein (CRP) and ceruloplasmin, have been associated with
      incident atrial fibrillation (AF). Genetic studies have not supported a causal
      relationship between CRP and AF, but the relationship between ceruloplasmin and
      AF has not been studied. The purpose of this Mendelian randomization study was to
      explore whether genetic polymorphisms in the gene encoding ceruloplasmin are
      associated with elevated ceruloplasmin levels, and whether such genetic
      polymorphisms are also associated with the incidence of AF. DESIGN: Genetic
      polymorphisms in the ceruloplasmin gene (CP) were genotyped in a population-based
      cohort study of men from southern Sweden (Malmo Preventive Project; n = 3900).
      Genetic polymorphisms associated with plasma ceruloplasmin concentration were
      also investigated for association with incident AF (n = 520) during a mean follow
      up of 29 years in the same cohort. Findings were replicated in an independent
      case-control sample (The Malmo AF cohort; n = 2247 cases, 2208 controls).
      RESULTS: A single nucleotide polymorphism (rs11708215, minor allele frequency
      0.12) located in the CP gene promoter was strongly associated with increased
      levels of plasma ceruloplasmin (P = 9 * 10(-10) ) and with AF in both the
      discovery cohort [hazard ratio 1.24 per risk allele, 95% confidence interval (CI)
      1.06-1.44, P = 0.006] and the replication cohort (odds ratio 1.13, 95% CI 1.02
      1.26, P = 0.02). CONCLUSIONS: Our findings indicate a causal role of
      ceruloplasmin in AF pathophysiology and suggest that ceruloplasmin might be a
      mediator in a specific inflammatory pathway that causally links inflammatory
      diseases and incidence of AF.

PMID- 24118453
TI  - A deficiency in chloroplastic ferredoxin 2 facilitates effective photosynthetic
      capacity during long-term high light acclimation in Arabidopsis thaliana.
AB  - Photosynthetic electron transport is the major energy source for cellular
      metabolism in plants, and also has the potential to generate excess reactive
      oxygen species that cause irreversible damage to photosynthetic apparatus under
      adverse conditions. Ferredoxins (Fds), as the electron-distributing hub in the
      chloroplast, contribute to redox regulation and antioxidant defense. However, the
      steady-state levels of photosynthetic Fd decrease in plants when they are exposed
      to environmental stress conditions. To understand the effect of Fd down
      regulation on plant growth, we characterized Arabidopsis thaliana plants lacking
      Fd2 (Fd2-KO) under long-term high light (HL) conditions. Unexpectedly, Fd2-KO
      plants exhibited efficient photosynthetic capacity and stable thylakoid protein
      complexes. At the transcriptional level, photoprotection-related genes were up
      regulated more in the mutant plants, suggesting that knockout Fd2 lines possess a
      relatively effective photo-acclimatory responses involving enhanced plastid redox
      signaling. In contrast to the physiological characterization of Fd2-KO under
      short-term HL, the plastoquinone pool returned to a relatively balanced redox
      state via elevated PGR5-dependent cyclic electron flow during extended HL. fd2
      pgr5 double mutant plants displayed severely impaired photosynthetic capacity
      under HL treatment, further supporting a role for PGR5 in adaptation to HL in the
      Fd2-KO plants. These results suggest potential benefits of reducing Fd levels in
      plants grown under long-term HL conditions. 

PMID- 24118452
TI  - Characterization of different regimens for initiating anagrelide in patients with
      essential thrombocythemia who are intolerant or refractory to their current
      cytoreductive therapy: results from the multicenter FOX study of 177 patients in
      France.
AB  - OBJECTIVES: To identify switch modalities used when initiating second- or third
      line anagrelide for essential thrombocythemia (ET), assess whether anagrelide is
      initiated consistently with Summary of Product Characteristics (SPC)
      recommendations, and determine whether different observed switch regimens have
      any relationship with maintenance, platelet response, or tolerability. METHODS:
      This observational study was conducted across 43 centers in France. High-risk
      patients (>60 yr of age and/or history of thrombosis and/or platelet count >1000
      * 10(9) /L) with ET starting second- or third-line anagrelide therapy were
      identified and monitored for 6 months. RESULTS: A total of 177 patients were
      enrolled. The SPC-recommended starting dose (1 mg/d) was used in 52.6% of
      patients; 0.5 mg/d was used in 41.1%. 77.1% of patients underwent an anagrelide
      dose increase during the study. At 6-month follow-up, 84.7% of patients (n =
      144/170) were still receiving anagrelide; 70.6% (n = 120/170) achieved a platelet
      response. A higher proportion of patients who discontinued previous cytoreductive
      therapy (CRT) after initiating anagrelide achieved a platelet response (n =
      34/39, 87.2%) vs. patients who discontinued their previous CRT before anagrelide
      initiation (n = 77/115, 67.0%). Platelet response rates were higher in patients
      whose anagrelide initiation was consistent (n = 100/133, 75.2%) vs. inconsistent
      (n = 20/37, 54.1%) with the SPC. The incidence of adverse drug reactions was
      lower in patients whose anagrelide treatment was consistent (n = 52/133, 39.1%)
      vs. inconsistent (n = 25/37, 67.6%) with the SPC. CONCLUSIONS: To our knowledge,
      the FOX study provides the first comprehensive real-world data on the modalities
      used when switching from previous CRT to anagrelide. Highest platelet responses
      were observed when previous CRT was discontinued after anagrelide initiation or
      when anagrelide was initiated consistently with the SPC. Safety data corresponded
      with the SPC.

PMID- 24118454
TI  - The magnitude of diabetes and its association with obesity in the slums of
      Nairobi, Kenya: results from a cross-sectional survey.
AB  - OBJECTIVES: To assess the prevalence, awareness, treatment and control of
      diabetes and to examine the relationship of obesity with raised blood glucose in
      the slums of Nairobi, Kenya. METHODS: We used data from a cross-sectional
      population-based survey, conducted in 2008-2009, involving a random sample of
      5190 (2794 men and 2396 women) adults aged >=18 years living in two slums -
      Korogocho and Viwandani - in Nairobi. RESULTS: The prevalence (weighted by
      sampling and response rates) of diabetes was 4.8% (95%CI 4.0-5.7) in women and
      4.0% (95%CI 3.3-4.7) in men. Less than a quarter of those found to have diabetes
      were aware of their condition among which just over half of men and three
      quarters of women reported being on any treatment in the 12 months preceding the
      survey. Overall, fewer than 5% of all people with diabetes had their blood sugar
      under control. Obesity and overweight were significantly associated with
      increased odds (1.7, 95%CI 1.1-2.6) of raised blood glucose only among women
      while adjusting for important covariates. CONCLUSION: The prevalence of diabetes
      in this impoverished population is moderately high, while the levels of
      awareness, treatment and control are quite low. In this population, obesity is an
      important risk factor for raised blood glucose particularly among women.
      Prevention and control strategies that target modifiable risk factors for
      diabetes and increase access to treatment and control in such disadvantaged
      settings are urgently needed.

PMID- 24118455
TI  - Robot-assisted laparoscopic retroperitoneal lymph node dissection for left
      clinical stage I non-seminomatous germ cell testicular cancer: focus on port
      placement and surgical technique.
AB  - The aim of our report was to describe the feasibility of robotic retroperitoneal
      lymph node dissection in the contemporary era. We suggest the linear port
      location and 90 degrees  robotic docking as the main key to minimizing instrument
      clashing and improving the range of surgical accessibility. 

PMID- 24118456
TI  - Relationship between habitual physical activity and gross motor skills is
      multifaceted in 5- to 8-year-old children.
AB  - Adequate motor skills are essential for children participating in age-related
      physical activities, and gross motor skills may play an important role for
      maintaining sufficient level of physical activity (PA) during life course. The
      purpose of this study was to examine the relationship between gross motor skills
      and PA in children when PA was analyzed by both metabolic- and neuromuscular
      based methods. Gross motor skills (KTK--Korperkoordinationstest fur Kinder and
      APM inventory--manipulative skill test) of 84 children aged 5-8 years (53
      preschoolers, 28 girls; 31 primary schoolers, 18 girls) were measured, and
      accelerometer-derived PA was analyzed using in parallel metabolic counts and
      neuromuscular impact methods. The gross motor skills were associated with
      moderate-to-high neuromuscular impacts, PA of vigorous metabolic intensity, and
      mean level of PA in primary school girls (0.5 < r < 0.7, P < 0.05), and with high
      impacts in preschool girls (0.3 < r < 0.5, P < 0.05). In preschool boys, moderate
      impacts, light-to-vigorous PA, and mean level of PA were associated with gross
      motor skills (0.4 < r < 0.7, P < 0.05). In conclusion, the result emphasizes an
      important relationship between gross motor skills and PA stressing both metabolic
      and neuromuscular systems in children. Furthermore, PA highly stressing
      neuromuscular system interacts with gross motor proficiency in girls especially.

PMID- 24118458
TI  - Potentials in the posterior fascicle: active role or passive bystander?

PMID- 24118457
TI  - Small MAF genes variants and chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is one of the most frequent hematological
      neoplasia worldwide. The abnormal accumulation of reactive oxygen species may be
      an important factor in CML development. The transcription factor NRF2 can
      regulate the transcription of a battery of antioxidant and detoxificant genes
      after heterodimerizing with small-Maf proteins. Although the participation of
      NRF2 in the development of chronic degenerative diseases has been thoroughly
      studied, the role of small-Maf genes has not been documented. We have identified
      polymorphisms in the three MAF genes (F, G and K) and assessed their association
      with CML. Over 266 subjects with CML and 399 unrelated healthy donors have been
      studied. After sequencing each MAF gene by Sanger technology, we found 17
      variants in MAFF gene, eight in MAFG and seven in MAFK. In the case-control
      study, the homozygote genotype CC for the rs9610915 SNP of MAFF was significantly
      associated with CML. The frequency of the ACC haplotype from MAFK was
      significantly lower than controls. After stratification by gender, the ACC and
      GTG haplotypes were associated only with males with CML. These novel data suggest
      an association between MAFF and MAFG and the development of CML. 

PMID- 24118459
TI  - Total laparoscopic modified radical hysterectomy with lymphadenectomy for
      endometrial cancer compared with laparotomy.
AB  - AIM: This is the first report to determine the feasibility and safety of total
      laparoscopic modified radical hysterectomy (TLMRH) in the treatment of presumed
      stage I endometrial cancer. METHODS: This was a retrospective study of 132
      consecutive patients who underwent surgery for early endometrial cancer. Thirty
      nine patients underwent TLMRH and bilateral salpingo-oophorectomy (BSO), and 93
      had a total abdominal extrafascial hysterectomy and BSO. Lymphadenectomy was
      performed in 87 patients. The groups were compared for epidemiological and
      clinical characteristics, surgical outcomes, hospital stay, lymph nodes
      harvested, and intraoperative and postoperative complications. RESULTS: The
      patients in the TLMRH group had less blood loss (42.9 +/- 76.3 vs 236.8 +/- 186.6
      mL, P < 0.0001), a similar number of lymph nodes removed (32.3 +/- 13.1 vs 28.0
      +/- 11.9, P = 0.15), less need for analgesia and a shorter hospital stay (9.3 +/-
      2.5 vs 14.6 +/- 12.6 days, P = 0.009) but longer operations (321.1 +/- 65.9 vs
      262.6 +/- 75.0 min, P < 0.0001) than those treated by laparotomy. In our study,
      we had no conversions from laparoscopy to laparotomy. No major complications
      occurred in the TLMRH group. The patients who underwent TLMRH had less intense
      postoperative pain than patients treated by laparotomy. The median length of
      vaginal cuff removed was 12.0 +/- 4.1 mm in the TLMRH group, and was 5.6 +/- 6.6
      mm in the laparotomy group (P < 0.0001). No patients demonstrated recurrence in
      either of the groups after a median follow-up of 48.5 months (range, 1-84).
      CONCLUSION: TLMRH is a safe and reliable alternative to open surgery in the
      management of early endometrial carcinoma, with a significantly reduced hospital
      stay and complications.

PMID- 24118460
TI  - Botulinum toxin B in the treatment of craniofacial hyperhidrosis.
AB  - BACKGROUND: Hyperhidrosis affects up to 3% of the population and negatively
      affects patients' quality of life. Craniofacial hyperhidrosis is a common
      complaint which has been successfully treated with botulinum toxin B (Btx B)
      since 2004 at our hidrosis clinics. OBJECTIVE: To evaluate the safety and
      clinical effect of Btx B in craniofacial hyperhidrosis. METHODS: The dermatology
      life quality index (DLQI) was monitored before and after treatment in 38 patients
      with craniofacial hyperhidrosis. Sweating before and after treatment was
      monitored by measuring trans epidermal water loss and by collecting gravimetric
      data. Global Assessment of Therapy in a 5-grade scale was captured. RESULTS: DLQI
      scores were significantly improved at follow-up 2-4 weeks posttreatment and
      sweating was significantly reduced. DLQI scores before treatment were 13 +/- 1
      (mean +/- SD) and posttreatment 5 +/- 1 which was highly statistically
      significant (P < 0.001). Sweating before treatment monitored with trans epidermal
      water loss was 52 +/- 31 g/m(2) /h which decreased to 18 +/- 7 g/m(2) /h (P <
      0.001) posttreatment. Gravimetric data yielded a sweat rate of 0.07 +/- 0.08
      mg/min at baseline, which consequently dropped to 0.02 +/- 0.05 mg/min (P < 0.05)
      posttreatment. Regarding the Global Assessment of Therapy 87% of the patients
      were satisfied (score 4-5) with the treatment result. In a 2-year follow-up, 74%
      returned for further treatments after a median time of 5 months. Side-effects
      were mild and most commonly reported was stiffness of the forehead and the
      eyebrows. CONCLUSIONS: In this prospective, uncontrolled study Btx B seems to be
      both a safe and effective treatment in craniofacial hyperhidrosis improving
      quality of life and reducing extreme sweating.

PMID- 24118462
TI  - Ultrasonography is more accurate than mammography in preoperative evaluations of
      palpable breast tumors in Chinese women.

PMID- 24118461
TI  - Determinants of pelvic organ prolapse among the women of the western part of
      Nepal: a case-control study.
AB  - AIM: This study was carried out in order to identify the determinants of pelvic
      organ prolapse (POP) among the women of the western part of Nepal. METHODS: This
      was a matched case-control study. Cases were defined as women diagnosed with
      third and fourth degree POP, and the control group consisted of women who were
      screened and confirmed of not having any degree of POP. Cases (n = 183) and
      controls (n = 183) were randomly selected and for each case, one control was
      selected, matched by age and place of residence. A semistructured interview was
      carried out to obtain the information for both groups. Bivariate analysis along
      with conditional logistic regression analysis was carried out to identify the
      association between selected variables with POP. RESULTS: The results showed the
      significant association between number of vaginal deliveries, tear of vagina in
      the last childbirth, sphincter damage in the last childbirth and duration of
      labor in the last childbirth with POP, after adjusting for educational status of
      the women, carrying heavy loads, type of usual work and incidence of diarrhea.
      CONCLUSION: The results suggest that prolonged labor along with vaginal delivery
      having sphincter and vaginal tear are the determinants of POP and program
      managers should strongly consider these factors to develop interventions
      targeting the prevention of POP.

PMID- 24118463
TI  - Use of prednisolone as monotherapy in the treatment of feline pemphigus
      foliaceus: a retrospective study of 37 cats.
AB  - BACKGROUND: Prednisone doses of up to 8 mg/kg/day have been used to treat feline
      pemphigus foliaceus (PF). Oral prednisolone has more favourable pharmacokinetics
      in cats than prednisone; therefore, lower doses of prednisolone may be effective
      in treating feline PF. HYPOTHESIS/OBJECTIVES: To assess the dose of prednisolone
      required to induce and maintain remission of PF in cats. ANIMALS: Thirty-seven
      client-owned cats with a diagnosis of PF treated with prednisolone monotherapy
      for induction of remission. METHODS: A retrospective analysis of records of a
      veterinary dermatology referral practice between the years of 1995 and 2013 was
      carried out. History, clinical signs, cytological and/or histopathological
      findings, lack of response to antimicrobials, absence of fungal hyphae on
      periodic acid Schiff staining and/or negative fungal culture and positive
      response to immunosuppressive therapy were used to confirm the diagnosis. Cats
      were included in the study if prednisolone was used as the monotherapy induction
      protocol. RESULTS: Complete remission was achieved within 8 weeks in 97% of cats
      with a median induction dose of 2 mg/kg prednisolone daily. In cats requiring
      ongoing treatment, 67% were maintained in remission with prednisolone
      monotherapy. The median maintenance dose was 1.2 mg/kg/week. In 14% of cats,
      medication was eventually discontinued. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Daily prednisolone at 2 mg/kg is an effective dose for inducing remission of PF
      in cats. Adverse effects were uncommon with this dose. In a small population,
      permanent remission may be induced. Secondary bacterial overgrowth and exudate in
      claw folds resolved in all cases with immunosuppressive therapy; therefore,
      antimicrobial therapy may be unnecessary.

PMID- 24118464
TI  - Electrical stimulation accelerates nerve regeneration and functional recovery in
      delayed peripheral nerve injury in rats.
AB  - The present study aims to investigate the potential of brief electrical
      stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed
      nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was
      transected, and the repair of nerve injury was delayed for different time
      durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the
      proximal nerve stump when the transected nerve stumps were bridged with a hollow
      nerve conduit (5 mm in length) after delayed periods. We found that the diameter
      and number of regenerated axons, the thickness of myelin sheath, as well as the
      number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were
      significantly increased by ES, suggesting that brief ES to proximal nerve stumps
      is capable of promoting nerve regeneration in DNIR with different delayed
      durations, with the longest duration of 24 weeks. In addition, the amplitude of
      compound muscle action potential (gastrocnemius muscle) and nerve conduction
      velocity were also enhanced, and gastrocnemius muscle atrophy was partially
      reversed by brief ES, indicating that brief ES to proximal nerve stump was able
      to improve functional recovery in DNIR. Furthermore, brief ES was capable of
      increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord
      in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the
      contributing factors to the beneficial effect of brief ES on DNIR. In conclusion,
      the present findings indicate the potential of using brief ES as a useful method
      to improve functional recovery for delayed repair of peripheral nerve lesions. 

PMID- 24118466
TI  - Acquired von Willebrand syndrome in patients with overt hypothyroidism: a
      prospective cohort study.
AB  - Numerous case reports have been published on acquired von Willebrand syndrome
      (aVWS) in patients with hypothyroidism, but no prospective studies have been
      published. The aim of this study was to investigate laboratory and clinical
      characteristics of aVWS in patients with newly diagnosed overt hypothyroidism. An
      observational cohort study was performed between May 2007 and February 2012.
      Consecutive hypothyroid patients before or within the first 48 h of replacement
      therapy were enrolled. At inclusion, blood was sampled for coagulation tests and
      bleeding history was documented by means of a standardized bleeding
      questionnaire. Repeat samples were obtained after restoration of euthyroidism.
      The prevalence of aVWS, defined as von Willebrand factor antigen (VWF:Ag) <=50%
      and/or VWF ristocetin activity (VWF:RCo) <=50%, was calculated. Patients with
      aVWS were subsequently divided into severe (VWF:Ag and/or VWF:RCo <=10%),
      moderate (VWF:Ag and/or VWF:RCo between 10 and 30%) or mild (VWF:Ag and/or
      VWF:RCo between 30 and 50%). A total of 90 patients were included among whom a
      prevalence of aVWS of 33% was found. There were no patients with severe aVWS.
      Eight patients (9%) had moderate aVWS and 21 (23%) had mild aVWS. Bleeding score
      was negatively correlated with both VWF:Ag (beta -0.32, P = 0.03) and VWF:RCo
      (beta -0.32, P = 0.02). After restoration of euthyroidism, VWF:Ag had
      significantly increased by 44%, VWF:RCo by 36%, factor VIII by 39%, and
      endogenous thrombin potential by 10%. aVWS has a high prevalence in hypothyroid
      patients. Highest bleeding scores in patients with lower VWF levels suggest
      clinical relevance. 

PMID- 24118465
TI  - An alternative outer membrane secretion mechanism for an autotransporter protein
      lacking a C-terminal stable core.
AB  - Autotransporter (AT) proteins are a broad class of virulence factors from Gram
      negative pathogens. AT outer membrane (OM) secretion appears simple in many
      regards, yet the mechanism that enables transport of the central AT 'passenger'
      across the OM remains unclear. OM secretion efficiency for two AT passengers is
      enhanced by approximately 20 kDa stable core at the C-terminus of the passenger,
      but studies on a broader range of AT proteins are needed in order to determine
      whether a stability difference between the passenger N- and C-terminus represents
      a truly common mechanistic feature. Yersinia pestis YapV is homologous to
      Shigella flexneri IcsA, and like IcsA, YapV recruits mammalian neural Wiskott
      Aldrich syndrome protein (N-WASP). In vitro, the purified YapV passenger is
      functional and rich in beta-sheet structure, but lacks a approximately 20 kDa C
      terminal stable core. However, the N-terminal 49 residues of the YapV passenger
      globally destabilize the entire YapV passenger, enhancing its OM secretion
      efficiency. These results indicate that the contributions of AT passenger
      sequences to OM secretion efficiency extend beyond a C-terminal stable core, and
      highlight a role of the passenger N-terminus in reducing passenger stability in
      order to facilitate OM secretion of some AT proteins.

PMID- 24118467
TI  - Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer.
AB  - Biliary tract cancer (BTC) has a generally poor prognosis. Furthermore, it is
      difficult to distinguish BTC from benign biliary disease (BBD) with commonly used
      modalities. Therefore, a novel biomarker to facilitate cancer detection is highly
      desirable. Recent studies have reported the use of circulating microRNAs (miRNAs)
      as biomarkers for cancers. The purpose of this study was to evaluate whether
      circulating miRNA-21 (miR-21) could be used as a biomarker for BTC. Plasma
      samples were obtained from 94 BTC patients, 50 healthy volunteers (HVs), and 23
      BBD patients. miR-21 levels in the samples were measured by qRT-PCR. Plasma miR
      21 levels in patients with BTC were significantly higher than in HVs or in
      patients with BBD (P < 0.0001 for both). Receiver-operator curve (ROC) curve
      analysis in differentiating BTC patients from HVs indicated that area under the
      curve (AUC), optimal sensitivity and specificity was 0.93, 85.1% and 100%,
      respectively, and those in differentiating BTC patients from BBD patients was
      0.83, 72.3%, 91.3%, respectively. Validation of these results indicated that the
      negative predictive value, positive predictive value, sensitivity, specificity,
      and accuracy in differentiating BTC patients from HVs was 76.6%, 98.6%, 84.0%,
      98.0%, and 88.9%, respectively, and those in differentiating BTC patients from
      BBD patients was 42.2%, 93.0%, 71.2%, 82.6%, and 72.6%, respectively. These sets
      of values were improved by combining miR-21 and CA19-9 measurements. Plasma miR
      21 is a novel diagnostic biomarker for BTC, and may be useful in distinguishing
      between BTC and BBD patients.

PMID- 24118468
TI  - Evaluation of closed-loop anesthesia delivery for propofol anesthesia in
      pediatric cardiac surgery.
AB  - OBJECTIVE: The objective of this study was to compare the feasibility of closed
      loop anesthesia delivery with manual control of propofol in pediatric patients
      during cardiac surgery. METHODS: Forty ASA II-III children, undergoing elective
      cardiac surgery under cardiopulmonary bypass (CPB) in a tertiary care hospital,
      were randomized to receive propofol either through a closed-loop anesthesia
      delivery system (CL group) or through traditional manual control (manual group)
      to achieve a target BIS of 50. Patients were induced and subsequently maintained
      with a propofol infusion. The propofol usage and the efficacy of closed-loop
      system in controlling BIS within +/-10 of the target were compared with that of
      manual control. RESULTS: The maintenance of BIS within +/-10 of target and
      intraoperative hemodynamic stability were similar between the two groups.
      However, induction dose of propofol was less in the CL group (2.06 +/- 0.79
      mg.kg(-1) ) than the manual group (2.95 +/- 1.03 mg.kg(-1) ) (P = 0.006) with
      less overshoot of BIS during induction in the closed-loop group (P = 0.007).
      Total propofol used in the off-CPB period was less in the CL group (6.29 +/- 2.48
      mg.kg(-1) h(-1) vs 7.82 +/- 2.1 mg.kg(-1) h(-1) ) (P = 0.037). Phenylephrine use
      in the pre-CPB period was more in the manual group (16.92 +/- 10.92 MUg.kg(-1) vs
      5.79 +/- 5.98 MUg.kg(-1) ) (P = 0.014). Manual group required a median of 18
      (range 8-29) dose adjustments per hour, while the CL group required none.
      CONCLUSION: This study demonstrated the feasibility of closed-loop controlled
      propofol anesthesia in children, even in challenging procedures such as cardiac
      surgery. Closed-loop system needs further and larger evaluation to establish its
      safety and efficacy.

PMID- 24118469
TI  - Validation of EUCAST zone diameter breakpoints against reference broth
      microdilution.
AB  - The European Committee on Antimicrobial Susceptibility Testing (EUCAST) began
      harmonizing clinical breakpoints in Europe 2002. In 2009, work to develop a disc
      diffusion method began and the first disc diffusion breakpoints calibrated to
      EUCAST clinical MIC breakpoints were published in December 2009. In this study we
      validated EUCAST clinical zone diameter breakpoints against the International
      Standard Organization (ISO) reference broth microdilution. A collection of 544
      isolates (238 Gram-negative and 306 Gram-positive) were tested against a panel of
      antimicrobial agents. Antimicrobial susceptibility testing was performed with
      broth microdilution as described by ISO and disc diffusion in accordance with
      EUCAST methodology. Inhibition zone diameters and MIC values were interpreted and
      categorized (S, I and R) according to EUCAST clinical breakpoint table version
      2.0. Categorical agreement (CA) as well as minor (mD), major (MD) and very major
      (VMD) discrepancies were determined. There was in general good correlation
      between susceptibility test results obtained with disc diffusion and broth
      microdilution. Overall CA was 97.3% for all combinations of organisms and
      antimicrobial agents (n = 5231) and the overall discrepancy rates were 110 (2.1%)
      mD, 24 (0.5%) MD and 7 (0.1%) VMD. The overall CA for Gram-positive and Gram
      negative organisms were 98.7% (2346 tests) and 96.2% (2942 tests), respectively.
      Seven VMD were observed, five for Gram-positive organisms (coagulase negative
      staphylococci (n = 2) and Staphylococcus aureus (n = 3)) and two for Gram
      negative organisms (Pseudomonas aeruginosa). Minor discrepancies were mainly
      observed in Gram-negatives and were related to different antimicrobial agents and
      species.

PMID- 24118470
TI  - Determining the effectiveness of illustrated communication material for
      communication with intubated patients at an intensive care unit.
AB  - Communication with non-speaking patients in intensive care unit is stress for
      both nurse and patients. Semi-experimental study that took place at a University
      Hospital was to develop illustrated material for patient communication and
      determine its effectiveness. The study sample consisted of 90 intubated patients
      at the Adult Cardiovascular Intensive Care Unit who had undergone open heart
      surgery. The patients were divided into the intervention and control groups. Data
      analysis was with descriptive statistics and the chi(2) test. The illustrated
      communication material was stated to be helpful by 77.8% and partially helpful by
      22.2% of the intervention group patients regarding the communication between the
      health-care staff and the patients. Control group patients had more difficulties
      communicating with the health-care staff. Illustrated communication material was
      an effective method in communicating with intubated patients. 

PMID- 24118471
TI  - The diagnostic value of contrast-enhanced ultrasonography in the assessment of
      perirenal hematomas in the early post-operative period after kidney
      transplantation.
AB  - BACKGROUND: Routine B-mode ultrasound examination (rB-US) is a current standard
      for the assessment of the transplanted kidney(KTx) in the early post-operative
      period. The alteration of perirenal hematoma (PH) echostructure over time limits
      their detectability and size assessment with rB-US. The aim of this study was to
      evaluate the diagnostic value of contrast-enhanced ultrasound (CE-US) in
      diagnosing PH of KTx in the early post-operative period. METHOD: Routine B-US and
      CE-US of KTx, performed in 102 patients in the early post-operative period, were
      analyzed. CE-US was performed after intravenous administration of 2.4 mL of
      sulfur hexafluoride solution. The data were analyzed with respect to the
      occurrence and thickness of PH. RESULT: The difference in echogenicity between PH
      and kidney parenchyma was modest in rB-US (mean of 5.7 dB). However, in CE-US,
      the difference in echogenicity was significantly increased (mean of 31.4 dB).
      Routine B-US did not allow PH to be recognized in 18 patients. The application of
      CE-US results in a twofold increase in PH detection when compared with rB-US
      (33.3% vs. 15.7%). CONCLUSION: US-CE examination is a valuable method for
      detection and assessment of PH size. Compared with rB-US, this technique may
      substantially increase the detectability of hemorrhagic complications in the
      direct post-operative period.

PMID- 24118473
TI  - Val158Met COMT polymorphism and risk of aggression in alcohol dependence.
AB  - Aggression, violence and antisocial behavior are common in alcoholism, but their
      biological basis is poorly understood. Several studies and recent meta-analyses
      indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT)
      Val158Met genotype may be associated with aggression, most often in methionine
      allele carriers. We tested this hypothesis in a sample of treatment-seeking
      alcohol-dependent in-patients (293 German patients and 499 controls, and
      additional 190 Polish patients as replication sample). As expected, patients with
      a history of violent or non-violent crime were more often male, had an earlier
      onset of alcoholism and more withdrawal seizures and delirium tremens, and were
      more likely to have a history of suicide attempts. COMT genotype was not
      associated with a history of violent or non-violent crime. More studies are
      needed on the neurobiological basis of aggression and violence in alcoholism. 

PMID- 24118474
TI  - Rituximab for remission induction in recurrent ANCA-associated glomerulonephritis
      postkidney transplant.
AB  - Kidney transplantation (KTX) is the treatment of choice for patients with end
      stage renal disease (ESRD) due to ANCA-associated vasculitis (AAV). Recurrent
      ANCA-associated glomerulonephritis (GN) occurs after KTX and may adversely affect
      allograft survival. Cyclophosphamide (CYC) combined with glucocorticoids has been
      the cornerstone of treatment for recurrent GN. Rituximab (RTX), a B-cell
      depleting monoclonal antibody, is approved for remission induction in AAV. We
      report the clinical presentation and outcomes of five KTX recipients treated with
      RTX for biopsy-confirmed recurrent GN. The median age at the time of KTX was 26
      years (four Caucasian, three females). All patients were in remission with four
      being ANCA positive at time of KTX. Recurrent GN occurred at a median of 26
      months post-KTX. All relapses were treated with RTX and glucocorticoids. Four
      patients achieved disease remission; the fifth patient was refractory to
      treatment with RTX and CYC. Follow-up biopsies (n = 3) showed resolution of
      active GN in two patients and persistent active GN in one patient. RTX is an
      alternative to CYC for remission induction in recurrent AAV-associated GN in KTX
      patients.

PMID- 24118475
TI  - Quantification of allergic and irritant patch test reactions using ImageJ.
AB  - BACKGROUND/AIMS: It is often difficult to differentiate between allergic and
      irritant patch test reactions by visual inspection. The purpose of this study was
      to test an image analysis-based method that differentiates between the two
      reactions by quantifying the degree of erythema at the patch test site. METHODS:
      A total of 172 Japanese patients were patch-tested with sodium lauryl sulfate
      (SLS) and nickel sulfate, followed by digital photography and visual evaluation
      of the patch test areas by dermatologists at 48 and 72 h. The digital images were
      converted to erythema index (EI) images by image processing, and changes in
      DeltaEI (the difference in the EI between the patch test site and the adjacent
      normal skin) values were analyzed. RESULTS: The DeltaEI was significantly
      increased at 72 h relative to that at 48 h for positive nickel sulfate reactions
      (P < 0.0001), while no significant difference in the DeltaEI was found for SLS
      reactions. CONCLUSION: Using image analysis, allergic patch test reactions may be
      distinguished from irritant reactions by evaluating the change in the degree of
      erythema at 48 and 72 h.

PMID- 24118476
TI  - Phylogeography and niche modelling of the relict plant Amborella trichopoda
      (Amborellaceae) reveal multiple Pleistocene refugia in New Caledonia.
AB  - Amborella trichopoda Baill. (Amborellaceae, Amborellales), the sole living member
      of the sister group to all other extant angiosperms, is endemic to New Caledonia.
      We addressed the intraspecific phylogeography of Amborella by investigating
      whether its present population genetic structure could be related to its current
      and past habitats. We found moderate range-wide genetic diversity based on
      nuclear microsatellite data and detected four well-differentiated, geographically
      distinct genetic groups using Bayesian clustering analyses. We modelled the
      ecological niche of Amborella based on the current climatic and environmental
      conditions. The predictive ability of the model was very good throughout the
      Central East mainland zone, but Amborella was predicted in the northern part of
      the island where this plant has not been reported. Furthermore, no significant
      barrier was detected based on habitat suitability that could explain the genetic
      differentiation across the area. Conversely, we found that the main genetic
      clusters could be related to the distribution of the suitable habitat at the last
      glacial maximum (LGM, c. 21,000 years BP), when Amborella experienced a dramatic
      96.5% reduction in suitable area. At least two lineages survived in distinct
      putative refugia located in the Massif des Levres and in the vicinity of Mount
      Aoupinie. Our findings finally confirmed the importance of LGM rainforest refugia
      in shaping the current intra- and interspecific diversity in New Caledonian
      plants and revealed the possibility of an as yet unreported refugium. The
      combination of niche modelling and population genetics thereby offered novel
      insight into the biogeographical history of an emblematic taxon.

PMID- 24118477
TI  - Phenotypic plasticity in the hepatic transcriptome of the European common frog
      (Rana temporaria): the interplay between environmental induction and geographical
      lineage on developmental response.
AB  - Phenotypic plasticity might facilitate adaptation to new environmental conditions
      through the enhancement of initial survival of organisms. Once a population is
      established, further adaptation and diversification may occur through adaptive
      trait evolution. While several studies have found evidence for this mechanism
      using phenotypic traits, much less is known at the level of gene expression.
      Here, we use an islands system of frog populations that show local adaptation and
      phenotypic plasticity to pool drying conditions in development time until
      metamorphoses. We examined gene expression differences in Rana temporaria tadpole
      livers with respect to pool drying at the source population and in response to
      simulated pool drying in the laboratory. Using a MAGEX cDNA microarray and
      quantitative real-time polymerase chain reaction (qPCR), we identified an
      increase in several gene transcripts in response to artificial pool drying
      including thyroid hormone receptor alpha and beta, carbamoyl phosphate synthetase
      1, ornithine transcarbamylase and catalase. In addition, these gene transcripts
      also showed greater abundance in island populations that developed faster. Hence,
      the gene transcripts were related to both constitutive response (higher levels in
      island populations that developed faster) and plastic response (increased
      abundance under decreasing water levels). This pattern is in accordance with
      genetic accommodation, which predicts similarities between plastic gene
      expression and constitutive expression in locally adapted populations. 

PMID- 24118478
TI  - Hyaluronic acid-induced alopecia: a novel complication.

PMID- 24118479
TI  - Pharmacists' views on and experiences with bowel cancer screening kits in
      Auckland, New Zealand.
AB  - OBJECTIVES: To explore the views of New Zealand pharmacists on bowel cancer
      screening, particularly with regards to faecal occult blood testing (FOBT) kits,
      self-perceived knowledge on FOBT kits and barriers, motivators and experiences
      with selling and counselling consumers with respect to FOBT kits. METHODS: Semi
      structured interviews were conducted face to face or by telephone with 20
      community pharmacists in the Auckland region. Interviews were recorded and
      transcribed verbatim and data were coded and analysed using NVivo software to
      identify key themes. KEY FINDINGS: Participant pharmacists believed that they
      were well placed to provide advice on FOBT kits to consumers. Barriers to selling
      the kits included cost and perceived lack of test sensitivity of the kits, poor
      consumer demand, pharmacists' lack of training and information, and a belief that
      selling FOBT kits was outside the pharmacists' scope of practice. Motivators to
      selling the kits included customer convenience, ease of use, confidence in the
      kits and embracing new roles for pharmacists. Pharmacists were concerned that use
      of the kits may increase the burden on the public health system through customer
      anxiety over test results; however, they agreed that there was a need for bowel
      cancer screening and awareness and that people concerned about bowel cancer
      should make visiting their general practitioner a priority. CONCLUSIONS:
      Pharmacists' views were mixed. Pharmacists' training and competence with respect
      to the provision of bowel cancer kits, and how a bowel cancer screening service
      can be developed to optimise public health outcomes, need to be addressed.

PMID- 24118480
TI  - Increased leaf mesophyll porosity following transient retinoblastoma-related
      protein silencing is revealed by microcomputed tomography imaging and leads to a
      system-level physiological response to the altered cell division pattern.
AB  - The causal relationship between cell division and growth in plants is complex.
      Although altered expression of cell-cycle genes frequently leads to altered organ
      growth, there are many examples where manipulation of the division machinery
      leads to a limited outcome at the level of organ form, despite changes in
      constituent cell size. One possibility, which has been under-explored, is that
      altered division patterns resulting from manipulation of cell-cycle gene
      expression alter the physiology of the organ, and that this has an effect on
      growth. We performed a series of experiments on retinoblastoma-related protein
      (RBR), a well characterized regulator of the cell cycle, to investigate the
      outcome of altered cell division on leaf physiology. Our approach involved
      combination of high-resolution microCT imaging and physiological analysis with a
      transient gene induction system, providing a powerful approach for the study of
      developmental physiology. Our investigation identifies a new role for RBR in
      mesophyll differentiation that affects tissue porosity and the distribution of
      air space within the leaf. The data demonstrate the importance of RBR in early
      leaf development and the extent to which physiology adapts to modified cellular
      architecture resulting from altered cell-cycle gene expression. 

PMID- 24118481
TI  - New insights, promises and challenges.

PMID- 24118482
TI  - Clinical spectrum and treatment of neuromyelitis optica spectrum disorders:
      evolution and current status.
AB  - Neuromyelitis optica (NMO) is an inflammatory neurologic disease clinically
      characterized by severe optic neuritis (ON) and transverse myelitis (TM). The
      relationship between NMO and multiple sclerosis (MS) has long been a matter of
      debate. However, the discovery of an NMO-specific autoantibody, NMO
      immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our
      understanding of the disease, and the clinical, magnetic resonance imaging (MRI),
      optical coherence tomography, and laboratory examinations have clarified unique
      features of NMO that are distinct from MS. The term NMO spectrum disorders
      (NMOSD) incorporating spatially limited forms was introduced, as patients with
      recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM
      (LETM) alone are also often AQP4 antibody-seropositive. Moreover, studies of
      seropositive cases have shown that more than half of them have brain lesions,
      some of which are unique to NMO, and can be the onset manifestation. Some
      clinical features of AQP4 antibody-seronegative NMO differ from seropositive, but
      it remains unknown whether they are pathologically distinct. Immunosuppressive
      treatments are effective for acute attacks and prevention of relapses of NMOSD,
      and new molecularly targeted drugs are under investigation. Importantly, some
      disease modifying drugs for MS may exacerbate NMOSD, making early differential
      diagnosis of the two diseases crucial. We review the evolving clinical spectrum,
      the updated clinical, MRI, neuro-ophthalmological and laboratory findings, and
      the current status of treatment in NMOSD. 

PMID- 24118483
TI  - Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica:
      a critical review of the literature.
AB  - Antibodies to aquaporin-4 (called NMO-IgG or AQP4-Ab) constitute a sensitive and
      highly specific serum marker of neuromyelitis optica (NMO) that can facilitate
      the differential diagnosis of NMO and classic multiple sclerosis. NMO-IgG/AQP4-Ab
      seropositive status has also important prognostic and therapeutic implications in
      patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis
      (ON). In this article, we comprehensively review and critically appraise the
      existing literature on NMO-IgG/AQP4-Ab testing. All available immunoassays
      including tissue-based (IHC), cell-based (ICC, FACS) and protein-based (RIPA,
      FIPA, ELISA, Western blotting) assays-and their differential advantages and
      disadvantages are discussed. Estimates for sensitivity, specificity, and positive
      and negative likelihood ratios are calculated for all published studies and
      accuracies of the various immunoassay techniques compared. Subgroup analyses are
      provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for
      various control groups (eg, MS vs. other controls). Numerous aspects of NMO
      IgG/AQP4-Ab testing relevant for clinicians (eg, impact of antibody titers and
      longitudinal testing, indications for repeat testing, relevance of CSF testing
      and subclass analysis, NMO-IgG/AQP4-Ab in patients with rheumatic diseases) as
      well as technical aspects (eg, AQP4-M1 vs. AQP4-M23-based assays, intact AQP4 vs.
      peptide substrates, effect of storage conditions and freeze/thaw cycles) and
      pitfalls are discussed. Finally, recommendations for the clinical application of
      NMO-IgG/AQP4-Ab serology are given. 

PMID- 24118485
TI  - Can the lens model provide a biomarker for Alzheimer's disease?

PMID- 24118484
TI  - Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO.
AB  - The water channel aquaporin-4 (AQP4) is the target of the immunoglobulin G
      autoantibody (AQP4-IgG) in neuromyelitis optica (NMO). AQP4 is expressed in foot
      processes of astrocytes throughout the central nervous system, as well as in
      skeletal muscle and epithelial cells in kidney, lung and gastrointestinal organs.
      Phenotype analysis of AQP4 knockout mice indicates the involvement of AQP4 in
      water movement into and out of the brain, astrocyte migration, glial scar
      formation and neuroexcitatory phenomena. AQP4 monomers form tetramers in
      membranes, which further aggregate to form supramolecular assemblies called
      orthogonal arrays of particles. AQP4-IgG is pathogenic in NMO by a mechanism
      involving complement- and cell-mediated astrocyte cytotoxicity, which produces an
      inflammatory response with oligodendrocyte injury and demyelination. AQP4
      orthogonal arrays are crucial in NMO pathogenesis, as they increase AQP4-IgG
      binding to AQP4 and greatly enhance complement-dependent cytotoxicity. Novel NMO
      therapeutics are under development that target AQP4-IgG or AQP4, including
      aquaporumab monoclonal antibodies and small molecules that block AQP4-IgG binding
      to AQP4, and enzymatic inactivation strategies to neutralize AQP4-IgG
      pathogenicity. 

PMID- 24118486
TI  - 39-year-old man with central diabetes insipidus.

PMID- 24118487
TI  - A 73 year-old man with a mass at the foramen magnum.

PMID- 24118488
TI  - 25 year-old woman with two spinal cord lesions.

PMID- 24118489
TI  - 78 year old male with dysphagia and dysarthria.

PMID- 24118491
TI  - Survey of animal bite injuries and their management for an estimate of human
      rabies deaths in N'Djamena, Chad.
AB  - OBJECTIVE: To estimate the annual human rabies incidence as a baseline prior to
      mass dog vaccination campaigns in N'Djamena, Chad. METHODS: Survey of animal
      bites, involving 50% of all healthcare providers in N'Djamena, from September
      2008 to April 2009. Of 86 people exposed to a suspected rabid animal, 50%
      received post-exposure vaccination and a further 8% had their wound cleaned. We
      estimated annual incidence of bites from suspected rabid animals of 12.9/100,000
      and an incidence of 0.7 human rabies deaths/100,000, resulting in 7 estimated
      deaths (95% confidence interval 4-10 deaths) per year in N'Djamena. 14% of bite
      victims sought help from veterinarians. CONCLUSIONS: Closer cooperation between
      physicians and veterinarians warrants more effective rabies control. The high
      proportion (42%) of potentially exposed people without post-exposure vaccination
      or wound treatment necessitates urgent attention.

PMID- 24118493
TI  - Renal artery stenosis: to intervene, or not to intervene, "that is the question".
AB  - Renal artery stenosis (RAS) due to atherosclerosis continues to be a major cause
      of secondary hypertension. It can also lead to renal dysfunction due to ischemic
      nephropathy. While major clinical trials have emphasized that medical management
      should be preferred over angioplasty and stenting for the treatment of renal
      artery stenosis, clinical scenarios continue to raise doubts about the optimal
      management strategy. Herein, we present two cases that were admitted with
      hypertensive emergency and renal function deterioration. Medical therapy failed
      to control the blood pressure and in one patient, renal failure progressed to a
      point where renal replacement therapy was required. Both patients underwent
      angioplasty (for >90% stenosis) and stent insertion with successful resolution of
      stenosis by interventional radiology. Postoperatively, blood pressure gradually
      decreased with improvement in serum creatinine. Dialysis therapy was
      discontinued. At 4- and 8-month follow-up, both patients continue to do well with
      blood pressure readings in the 132-145/70-90 mmHg range. This article highlights
      the importance of percutaneous interventions in the management of atherosclerotic
      RAS and calls for heightened awareness and careful identification of candidates
      who would benefit from angioplasty and stent insertion. 

PMID- 24118492
TI  - Renal function after radical nephrectomy: development and validation of
      predictive models in Japanese patients.
AB  - OBJECTIVES: To develop and validate predictive models for postoperative estimated
      glomerular filtration rate and risk of chronic kidney disease after radical
      nephrectomy in Japanese patients. METHODS: The present retrospective study
      included a development cohort of 209 patients without preoperative chronic kidney
      disease who underwent radical nephrectomy between 1994 and 2008, and were
      followed up for longer than 3 years, and a validation cohort of 144 similar such
      patients. Univariate and multivariate linear regression or logistic regression
      analyses were carried out to identify the independent predictors of estimated
      glomerular filtration rate or chronic kidney disease 3 years after radical
      nephrectomy. Incorporating all independent predictors, predictive models for
      postoperative renal function were developed and externally validated. RESULTS:
      Age, the presence of diabetes mellitus, and preoperative estimated glomerular
      filtration rate were independent predictors of both postoperative estimated
      glomerular filtration rate and chronic kidney disease. A formula for predicting
      the postoperative estimated glomerular filtration rate and a nomogram for
      predicting the risk of postoperative chronic kidney disease were developed. The
      adjusted R(2) of the formula and area under the receiver operating characteristic
      curves of the nomogram were 0.446 and 0.865 in the development cohort, and 0.396
      and 0.787 in the validation cohort, respectively. CONCLUSIONS: We developed and
      validated novel predictive models for the postoperative renal function 3 years
      after radical nephrectomy in Japanese patients.

PMID- 24118494
TI  - Increased proatherogenic monocyte-platelet cross-talk in monocyte subpopulations
      of patients with stable coronary artery disease.
AB  - BACKGROUND: Monocytes and platelets are important cellular mediators of
      atherosclerosis. Human monocytes can be divided into CD14(++) CD16(-) , CD14(++)
      CD16(+) and CD14(+) CD16(++) cells, which differ in their functional properties.
      The aim of this study was to examine monocyte subset distribution, monocyte
      platelet aggregate (MPA) formation and expression of CCR5, the receptor of the
      platelet-derived chemokine CCL5, and to determine whether these parameters are
      altered in individuals with coronary atherosclerosis. METHODS: Peripheral blood
      cells from 64 healthy blood donors (HBDs) and 60 patients with stable coronary
      artery disease (CAD) were stained with antibodies against CD14, CD16, CD42b and
      CCR5 and analysed by flow cytometry. Circulating CCL5 levels were determined
      using an enzyme-linked immunosorbent assay. RESULTS: In patients with CAD, the
      relative proportion of the CD14(++) CD16(-) monocyte subset was elevated (P <
      0.05) and of the CD14(+) CD16(++) subset was reduced (P < 0.001) compared with
      the HBD group. Furthermore, MPA formation significantly increased in patients
      with CAD in all three monocyte subsets. In both study groups, the majority of
      CCR5(+) cells was detected in CD14(++) CD16(+) monocytes (P < 0.001 versus
      CD14(++) CD16(-) and CD14(+) CD16(++) ), although the CCR5(+) monocyte number was
      reduced in patients with CAD (CD14(++) CD16(-) /CD14(+) CD16(++) , P < 0.001;
      CD14(++) CD16(+) , P < 0.05) compared with the HBD group, particularly in those
      who were not taking statins. Ex vivo incubation of monocytes from HBDs with
      plasma from patients with CAD also decreased CCR5(+) expression (P < 0.05 versus
      plasma from HBDs). Serum CCL5 levels were similar in both groups. CONCLUSIONS:
      The increased monocyte-platelet cross-talk in patients with CAD might have
      contributed to atherosclerosis progression. The decreased CCR5(+) monocyte
      numbers in patients with CAD could have resulted from CCR5(+) cell recruitment
      into atherosclerotic lesions or CCR5 downregulation in response to circulating
      factors.

PMID- 24118495
TI  - Using ground reaction force to predict knee kinetic asymmetry following anterior
      cruciate ligament reconstruction.
AB  - Asymmetries in sagittal plane knee kinetics have been identified as a risk factor
      for anterior cruciate ligament (ACL) re-injury. Clinical tools are needed to
      identify the asymmetries. This study examined the relationships between knee
      kinetic asymmetries and ground reaction force (GRF) asymmetries during athletic
      tasks in adolescent patients following ACL reconstruction (ACL-R). Kinematic and
      GRF data were collected during a stop-jump task and a side-cutting task for 23
      patients. Asymmetry indices between the surgical and non-surgical limbs were
      calculated for GRF and knee kinetic variables. For the stop-jump task, knee
      kinetics asymmetry indices were correlated with all GRF asymmetry indices (P <
      0.05), except for loading rate. Vertical GRF impulse asymmetry index predicted
      peak knee moment, average knee moment, and knee work (R(2)  >= 0.78, P < 0.01)
      asymmetry indices. For the side-cutting tasks, knee kinetic asymmetry indices
      were correlated with the peak propulsion vertical GRF and vertical GRF impulse
      asymmetry indices (P < 0.05). Vertical GRF impulse asymmetry index predicted peak
      knee moment, average knee moment, and knee work (R(2)  >= 0.55, P < 0.01)
      asymmetry indices. The vertical GRF asymmetries may be a viable surrogate for
      knee kinetic asymmetries and therefore may assist in optimizing rehabilitation
      outcomes and minimizing re-injury rates. 

PMID- 24118496
TI  - You can't know where you're going until you know where you've been: the clinical
      relevance of differences in accurate assessment of catheter location with mapping
      technologies.

PMID- 24118497
TI  - Effectiveness of selective vaginal tightening on sexual function among
      reproductive aged women in Iran with vaginal laxity: a quasi-experimental study.
AB  - AIM: Sexuality is an important part of women's health, quality of life and
      general well-being. Vaginal laxity may cause sexual dissatisfaction thereby
      causing some women to demand vaginal tightening surgeries. This study aimed to
      evaluate the sexual function preoperative and 6 months after selective vaginal
      tightening in women of reproductive age in Iran with vaginal laxity. METHODS: A
      quasi-experimental study was carried out on 79 women with vaginal laxity. All the
      women were requested to complete the questionnaire, which contained
      sociodemographic and Female Sexual Function Index (FSFI) questions preoperatively
      and 6 months after vaginal tightening. Data were analyzed using a paired
      Student's t-test, Wilcoxon rank sum test and Mann-Whitney U-test. RESULTS: The
      mean age of participants was 34.02 +/- 5.30 years. The average total FSFI score
      increased from 24.19 +/- 3.09 to 26.92 +/- 3.41 (P < 0.001) after surgery. The
      scores for libido, arousal, orgasm and satisfaction domain were significantly
      improved, but a high level of dyspareunia and low vaginal lubrication were noted
      (P < 0.001). CONCLUSION: Sexual function was improved 6 months after vaginal
      tightening. This indicates that elective vaginal tightening had a positive effect
      on the sexual function in women. However, the increase in dyspareunia and
      decrease in lubrication may limit the application of this type of surgery.
      Further studies with longer follow-up are required to verify the long-term
      results of vaginal tightening.

PMID- 24118498
TI  - MYC translocation partner gene determines survival of patients with large B-cell
      lymphoma with MYC- or double-hit MYC/BCL2 translocations.
AB  - In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations
      have been associated with inferior survival. We hypothesised that the negative
      prognostic impact of MYC translocation was determined by an immunoglobulin MYC
      translocation partner gene (IG-MYC), as opposed to a non-immunoglobulin partner
      gene (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC
      and BCL2 translocations were identified by fluorescent in situ hybridisation
      (FISH) with split probes. MYC translocation partner gene was identified by
      IGH/MYC fusion probes and/or kappa/lambda split probes. Clinical data were
      collected from patient files. MYC translocation was identified in 28/225
      patients. IG-MYC translocation partner gene was identified in 12/24 patients. DH
      translocation was identified in 23/228 patients. IG-MYC translocation partner
      gene was identified in 9/19 DH patients. Neither MYC-nor DH translocation showed
      correlation with survival. However, MYC translocation with IG-MYC translocation
      partner gene was associated with worse OS compared with both MYC translocation
      with nonIG-MYC translocation partner gene (P = 0.02) as well as absence of MYC
      translocation (P = 0.03). In patients with DH a similar, however, stronger
      correlation was seen (P = 0.003 and P = 0.0004 respectively). MYC - or DH
      translocation with nonIG-MYC translocation partner gene was not associated with
      worse overall survival (P = 0.2 and P = 0.3 respectively). Most patients received
      Rituximab (86%) and CHOP/CHOP-like chemotherapy regimes (81%). We suggest that
      prognostic stratification of LBCL patients by MYC and/or DH translocations should
      include identification of MYC translocation partner gene because approximately
      half of the cases harbour nonIG-MYC translocation partner genes with no or minor
      influence on survival.

PMID- 24118499
TI  - Chromosomal instability associated with a novel BLM frameshift mutation (c.1980
      1982delAA) in two unrelated Tunisian families with Bloom syndrome.
AB  - The Bloom syndrome (BS) is an autosomal recessive disorder associated with
      dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show
      genomic instability, particularly an hyper exchange between the sister chromatids
      due to a defective processing of the DNA replication intermediates. It is caused
      by mutations in the BLM gene which encodes a member of the RecQ family of DExH
      box DNA helicases. In this study, we reported cytogenetic, BLM linkage and
      mutational analyses for two affected Tunisian families. The Cytogenetic
      parameters were performed by chromosomal aberration (CA) and sister chromatid
      exchange (SCE) assays and results showed a significant increase in mean frequency
      of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping
      revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM
      gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift
      mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated
      protein (p.Lys662fsX5). The truncated protein could explain genomic instability
      and its related symptoms in the BS patients. The screening of this mutation is
      useful for BS diagnosis confirmation in Tunisian families. 

PMID- 24118500
TI  - Treatment expectations and satisfaction of treatment-refractory opioid-dependent
      patients in RIOTT, the Randomised Injectable Opiate Treatment Trial, the UK's
      first supervised injectable maintenance clinics.
AB  - INTRODUCTION AND AIMS: The study investigates patients' pre-treatment
      expectations of, and post-treatment satisfaction with, supervised injectable
      opiate treatment delivered within UK's first such clinics within the Randomised
      Injectable Opiate Treatment Trial (RIOTT) (ISRCTN0133807). DESIGN AND METHODS:
      Data were collected from 127 chronic heroin addicts recruited to RIOTT and
      randomised to receive supervised injectable (heroin or methadone) treatment or
      optimised oral maintenance treatment at supervised injectable maintenance clinics
      in London, Darlington and Brighton. RESULTS: Of 127 RIOTT patients, 113 (89%)
      provided responses to structured enquiry about treatment expectations, and 94
      (74%) subsequent responses about treatment satisfaction (at six months). Patients
      were hoping that injectable heroin treatment would: reduce substance misuse
      (81%); help achieve normality, routine and structure (16%); and increase
      education and work prospects (15%). At six months, an area of treatment
      satisfaction most commonly reported by all three trial groups was reduced
      substance misuse (supervised injectable heroin 59%, supervised injectable
      methadone 56%, optimised oral methadone 54%). Most found supervision acceptable,
      but some desired modifications were also identified. DISCUSSION AND CONCLUSIONS:
      Patients previously considered non-responsive to treatment appear to have similar
      treatment expectations and aspirations as other drug users in treatment.
      Supervised injectable opioid treatment patients consistently reported treatment
      satisfaction but also that more could be done to optimise aspects of current
      arrangement. This raised the challenging issue of the extent to which opinions of
      patients need to be taken into consideration in shaping future treatment
      provision. Future research may need to examine the extent of expectations 'fit'
      and the relationship between treatment sought and received.

PMID- 24118501
TI  - Subcutaneous mastectomy for juvenile mammary hypertrophy: a clinical experience.

PMID- 24118502
TI  - Thrombus just beneath a retrievable inferior vena cava filter in a pregnant woman
      with deep vein thrombosis: its removal requiring catheter thrombus fragmentation
      with fibrinolysis.
AB  - Recently, transient inferior vena cava (IVC) filters have been employed to
      protect against pulmonary embolism (PE) in pregnant women with deep vein
      thrombosis. A 34-year-old primiparous Japanese woman with a history of myomectomy
      was diagnosed with deep vein thrombosis by ultrasound at 27 weeks of gestation.
      Unfractionated heparin was administered, which soon ameliorated swelling in the
      right thigh. A transient IVC filter was implanted just before cesarean section.
      An enhanced computed tomography scan 2 days after cesarean section revealed a
      wide thrombus just distal to the filter. We performed catheter thrombus
      fragmentation with fibrinolysis just before the removal of the IVC filter,
      resulting in re-canalization of blood flow. No significant PE occurred. Although
      a transient IVC filter may work well for the prophylaxis of PE during labor and
      delivery, catheter fragmentation with fibrinolysis may become necessary at
      removal of the filter. 

PMID- 24118503
TI  - Parallelism in the brain's visual form system.
AB  - We used magnetoencephalography (MEG) to determine whether increasingly complex
      forms constituted from the same elements (lines) activate visual cortex with the
      same or different latencies. Twenty right-handed healthy adult volunteers viewed
      two different forms, lines and rhomboids, representing two levels of complexity.
      Our results showed that the earliest responses produced by lines and rhomboids in
      both striate and prestriate cortex had similar peak latencies (40 ms) although
      lines produced stronger responses than rhomboids. Dynamic causal modeling (DCM)
      showed that a parallel multiple input model to striate and prestriate cortex
      accounts best for the MEG response data. These results lead us to conclude that
      the perceptual hierarchy between lines and rhomboids is not mirrored by a
      temporal hierarchy in latency of activation and thus that a strategy of parallel
      processing appears to be used to construct forms, without implying that a
      hierarchical strategy may not be used in separate visual areas, in parallel. 

PMID- 24118504
TI  - Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous
      gastric cancer.
AB  - Scirrhous gastric cancer is associated with abundant stroma and frequently
      develops into peritoneal carcinomatosis with malignant ascites. Although
      malignant ascites is among the most deadly diseases worldwide, its molecular
      pathogenesis is poorly understood. We investigated the role of hepatocyte growth
      factor (HGF) in the production of peritoneal carcinomatosis with malignant
      ascites. We examined three scirrhous and three non-scirrhous human gastric cancer
      cell lines for the production of peritoneal carcinomatosis in vivo and responses
      to HGF in vitro. Furthermore, clinical scirrhous gastric cancer specimens were
      examined for HGF production. Among the six cell lines examined, only two
      scirrhous cell lines (NUGC4 and GCIY) produced peritoneal carcinomatosis with
      massive ascites after intraperitoneal injection in nude mice. Their proliferation
      was stimulated by exogenous HGF in vitro. On the other hand, a non-scirrhous cell
      line, MKN45, with MET amplification generated peritoneal tumors but not ascites.
      MET tyrosine kinase inhibitors, crizotinib and TAS-115, inhibited HGF-stimulated
      proliferation of NUGC4 and GCIY as well as constitutive proliferation of MKN45.
      Furthermore, crizotinib and TAS-115 prolonged the survival of mice bearing
      established tumors by NUGC4 or MKN45. In clinical specimens, HGF was markedly
      produced by stromal fibroblasts. Malignant ascitic fluids from patients with
      peritoneal carcinomatosis contained high levels of HGF. Our results strongly
      suggest that paracrine HGF-induced activation of MET-mediated signaling pathways
      plays an important role in the pathogenesis of peritoneal carcinomatosis in
      scirrhous gastric cancer. Thus, MET signaling pathway may be a potential
      therapeutic target for peritoneal carcinomatosis of gastric cancer, even without
      MET amplification. 

PMID- 24118505
TI  - O-linked protein glycosylation in Mycoplasma.
AB  - Although mycoplasmas have a paucity of glycosyltransferases and
      nucleotidyltransferases recognizable by bioinformatics, these bacteria are known
      to produce polysaccharides and glycolipids. We show here that mycoplasmas also
      produce glycoproteins and hence have glycomes more complex than previously
      realized. Proteins from several species of Mycoplasma reacted with a glycoprotein
      stain, and the murine pathogen Mycoplasma arthritidis was chosen for further
      study. The presence of M. arthritidis glycoproteins was confirmed by high
      resolution mass spectrometry. O-linked glycosylation was clearly identified at
      both serine and threonine residues. No consensus amino acid sequence was evident
      for the glycosylation sites of the glycoproteins. A single hexose was identified
      as the O-linked modification, and glucose was inferred by (13) C-labelling to be
      the hexose at several of the glycosylation sites. This is the first study to
      conclusively identify sites of protein glycosylation in any of the mollicutes. 

PMID- 24118506
TI  - Intranasal sufentanil/ketamine analgesia in children.
AB  - BACKGROUND: The management of procedural pain in children ranges from physical
      restraint to pharmacological interventions. Pediatric formulations that permit
      accurate dosing, are accepted by children and a have a rapid onset of analgesia
      are lacking. OBJECTIVES: To investigate a pediatric formulation of intranasal
      sufentanil 0.5 mcg.kg(-1) and ketamine 0.5 mg.kg(-1) for procedural pain and to
      characterize the pharmacokinetic (PK) profile. METHODS: Fifty children (>=10 kg)
      scheduled for a painful procedure were included in this prospective nonrandomized
      open-label clinical trial. Thirteen of these children had central venous access
      for drug assay sampling; enabling a compartmental PK analysis using nonlinear
      mixed-effects models. Pain intensity before and during the procedure was measured
      using age-appropriate pain scales. Heart rate, oxygen saturation and sedation
      were recorded. RESULTS: Children had a mean age of 8.8 (sd 4.9) years and weight
      35.2 (sd 20.1) kg. Sufentanil/ketamine nasal spray was effective (procedural pain
      intensity scores <=5 (0-10)) in 78% of the painful procedures. The spray was well
      accepted by 94% of the children. Oxygen saturation and heart rate remained
      stable, and sedation was minimal. The bioavailability of sufentanil and ketamine
      was 24.6% and 35.8%, respectively. Maximum plasma concentration (Cmax) of
      sufentanil was 0.042 mcg.l(-1) (coefficient of variation (CV) 12.9%) at 13.8 min
      (CV 12.4%) (Tmax). Cmax for ketamine was 0.102 mg.l(-1) (CV 10.8%), and Tmax was
      8.5 min (CV 17.3%). CONCLUSION: Sufentanil/ketamine nasal spray provided rapid
      onset of analgesia for a variety of painful procedures with few adverse effects
      and has promising features for use in pediatric procedural pain management.

PMID- 24118507
TI  - Utility and futility of early liver re-transplantation.

PMID- 24118508
TI  - Phototherapy approaches in treatment of oral lichen planus.
AB  - Oral lichen planus (OLP) is a chronic immunologic mucocutaneous inflammatory
      disease of the oral mucosa. Since the etiopathology of OLP is idiopathic,
      treatment is usually symptomatic, therefore showing low predictability.
      Currently, topical corticosteroids are widely accepted as the standard therapy.
      However, for patients unresponsive to standard therapy for OLP, new treatment
      modalities have been sought. Phototherapy has recently been accepted as an
      alternative or adjunctive treatment modality for many conditions in medicine and
      dentistry. The aim of this study is to present the advantages and disadvantages
      of the different kinds of phototherapy used in treatment of OLP (UV phototherapy,
      lasers, and photodynamic therapy). The main outcome measures compared were
      improvement of signs and symptoms and OLP recurrence. Although some phototherapy
      techniques in the selected articles have demonstrated limited effects, there is
      no solid basis in evidence for the effectiveness of any of these treatments for
      OLP. Therefore, further research, especially randomized controlled clinical
      trials with long-term follow-up, is needed to give any solid recommendation on
      the use of phototherapy in the field of OLP treatment. 

PMID- 24118509
TI  - Triple monoamine uptake inhibitors demonstrate a pharmacologic association
      between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.
AB  - Approximately 30% of current drinkers in the United States drink excessively, and
      are referred to as problem/hazardous drinkers. These individuals, who may not
      meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, or
      both. Given their high prevalence, interventions that reduce the risk of binge
      and heavy drinking have important public health implications. Impulsivity has
      been repeatedly associated with excessive drinking in the clinical literature. As
      impulsivity is correlated with, and may play a critical role in, the initiation
      and maintenance of excessive drinking, this behavior may be an important target
      for therapeutic intervention. Hence, a better understanding of pharmacological
      treatments capable of attenuating excessive drinking and impulsivity may markedly
      improve clinical outcomes. The high-alcohol-preferring (HAP) mice represent a
      strong rodent model to study the relationship between impulsivity and excessive
      alcohol drinking, as recent evidence indicates they consume high levels of
      alcohol throughout their active cycle and are innately impulsive. Using this
      model, the present study demonstrates that the triple monoamine uptake inhibitors
      (TUIs) amitifadine and DOV 102, 677 effectively attenuate binge drinking, heavy
      drinking assessed via a 24-hour free-choice assay, and impulsivity measured by
      the delay discounting procedure. In contrast, 3-PBC, a GABA-A alpha1 preferring
      ligand with mixed agonist-antagonist properties, attenuates excessive drinking
      without affecting impulsivity. These findings suggest that in HAP mice, monoamine
      pathways may predominate as a common mechanism underlying impulsivity and
      excessive drinking, while the GABAergic system may be more salient in regulating
      excessive drinking. We further propose that TUIs such as amitifadine and DOV 102,
      677 may be used to treat the co-occurrence of impulsivity and excessive drinking.

PMID- 24118510
TI  - Efficacy and safety of and patient satisfaction with injectable hyaluronic acid
      with 0.3% lidocaine hydrochloride for the treatment of superficial perioral lines
      or superficial lateral canthal lines.
AB  - BACKGROUND: It is commonly requested that perioral and lateral canthal rhytides,
      which result from extrinsic and intrinsic factors, be rejuvenated. OBJECTIVE: To
      valuate the safety and efficacy of and patient satisfaction with injectable
      hyaluronic acid (HA) with 0.3% lidocaine hydrochloride in reducing superficial,
      vertical perioral wrinkles and superficial, horizontal, lateral canthal rhytides.
      MATERIALS AND METHODS: This was a two-center, evaluator-masked, 180-day study in
      which 40 patients with moderate to severe superficial, vertical perioral lines or
      superficial, horizontal, lateral canthal lines were treated at their baseline
      visit with up to three 0.9-mL syringes of HA (5.5 mg/mL) with 0.3% lidocaine
      hydrochloride. The investigator and a blinded evaluator assessed patients 7 days
      after treatment and then every 30 days after the initial treatment session for
      180 days. RESULTS: Subjects experienced statistically significant improvement in
      their superficial, vertical perioral lines and superficial, horizontal, lateral
      canthal lines and maintained those results for 180 and 120 days, respectively.
      Three patients experienced delayed-onset periocular nodule formation associated
      with swelling and erythema at sites of injection, which were histologically
      consistent with a granulomatous reaction to the product. CONCLUSION: Injectable
      HA with a particle size of 350 MUm was efficacious and resulted in high patient
      improvement scores in improving moderate to severe superficial, vertical perioral
      lines and superficial, horizontal, lateral canthal lines. Three of the 40
      enrolled patients demonstrated granuloma formation.

PMID- 24118511
TI  - Validation of a novel translumbar ultrasound technique for measuring renal
      dimensions in horses.
AB  - A reliable method for obtaining renal ultrasonographic measurements in the horse
      is important for diagnosis and monitoring of clinical renal disease. The aims of
      this prospective study were to develop and validate a novel translumbar
      ultrasound technique for measuring renal dimensions in horses. Six Thoroughbred
      or Thoroughbred part bred horses were recruited. All horses were scheduled for
      euthanasia due to reasons unrelated to the kidneys. Two observers recorded renal
      length, width, and depth; and dimensions of the cortex, medulla, pyramids, and
      pelvis for both kidneys in each horse using novel translumbar and conventional
      transabdominal ultrasound methods. The same measurements were recorded from post
      mortem renal specimens. Both kidneys were consistently identified by both methods
      in the 15-17th intercostal spaces and paralumbar fossa. Using the translumbar
      technique, maximal dimensions were obtained for the left kidney in the 16th
      intercostal space (length 16.2 +/- 2.0 cm, width 11.8 +/- 0.5 cm, depth 6.4 +/-
      0.9 cm) and for the right kidney in the 15th intercostal space (length 16.1 +/-
      1.2 cm, width 13.4 +/- 1.2 cm, depth 6.7 +/- 0.7 cm). Renal dimensions obtained
      by transabdominal and translumbar projections did not differ (P > 0.05). Good
      correlations were found between overall renal dimensions and post-mortem
      measurements for both ultrasound techniques (r(2) > 0.8), but were better for the
      translumbar method (mean r(2) = 0.92 cf. 0.88). Good-to-excellent reliability was
      found for all translumbar ultrasound measurements except for the renal cortex.
      Reproducibility was better for the larger (overall length, width, and depth) than
      the smaller (cortex, medulla, and pyramids) structures. Findings indicated that
      translumbar ultrasonography is a valid method for measuring renal dimensions in
      horses.

PMID- 24118512
TI  - Early to middle gestational exposure to diethylstilbestrol impairs the
      development of labyrinth zone in mouse placenta.
AB  - This study was performed to clarify the involvement of impaired labyrinth zone
      (LZ) of the placenta in the developmental toxicity of diethylstilbestrol (DES).
      DES at 10 MUg/kg per day was administered orally to mice on days 4 through 8 of
      gestation. Histological observation of the LZ and determination of blood glucose
      levels in dam and fetus were performed on day 13. A high frequency of embryonic
      death was observed in the DES group. DES induced the underdevelopment of the
      plexus vasculosus, extensive maternal blood space and the decreased expression of
      glucose transporters in the LZ, and a reduction of the glucose level in embryos.
      These findings suggest that impaired LZ development may be related to the
      embryolethality of DES. 

PMID- 24118513
TI  - Phospholipid:diacylglycerol acyltransferase-mediated triacylglycerol biosynthesis
      is crucial for protection against fatty acid-induced cell death in growing
      tissues of Arabidopsis.
AB  - Phospholipid:diacylglycerol acyltransferase (PDAT) and diacylglycerol:acyl CoA
      acyltransferase play overlapping roles in triacylglycerol (TAG) assembly in
      Arabidopsis, and are essential for seed and pollen development, but the
      functional importance of PDAT in vegetative tissues remains largely unknown.
      Taking advantage of the Arabidopsis tgd1-1 mutant that accumulates oil in
      vegetative tissues, we demonstrate here that PDAT1 is crucial for TAG
      biosynthesis in growing tissues. We show that disruption of PDAT1 in the tgd1-1
      mutant background causes serious growth retardation, gametophytic defects and
      premature cell death in developing leaves. Lipid analysis data indicated that
      knockout of PDAT1 results in increases in the levels of free fatty acids (FFAs)
      and diacylglycerol. In vivo 14C-acetate labeling experiments showed that,
      compared with wild-type, tgd1-1 exhibits a 3.8-fold higher rate of fatty acid
      synthesis (FAS), which is unaffected by disruption or over-expression of PDAT1,
      indicating a lack of feedback regulation of FAS in tgd1-1. We also show that
      detached leaves of both pdat1-2 and tgd1-1 pdat1-2 display increased sensitivity
      to FFA but not to diacylglycerol. Taken together, our results reveal a critical
      role for PDAT1 in mediating TAG synthesis and thereby protecting against FFA
      induced cell death in fast-growing tissues of plants.

PMID- 24118514
TI  - In silico calculated affinity of FVIII-derived peptides for HLA class II alleles
      predicts inhibitor development in haemophilia A patients with missense mutations
      in the F8 gene.
AB  - Forty per cent of haemophilia A (HA) patients have missense mutations in the F8
      gene. Yet, all patients with identical mutations are not at the same risk of
      developing factor VIII (FVIII) inhibitors. In severe HA patients, human leucocyte
      antigen (HLA) haplotype was identified as a risk factor for onset of FVIII
      inhibitors. We hypothesized that missense mutations in endogenous FVIII alter the
      affinity of the mutated peptides for HLA class II, thus skewing FVIII-specific T
      cell tolerance and increasing the risk that the corresponding wild-type FVIII
      derived peptides induce an anti-FVIII immune response during replacement therapy.
      Here, we investigated whether affinity for HLA class II of wild-type FVIII
      derived peptides that correspond to missense mutations described in the
      Haemophilia A Mutation, Structure, Test and Resource database is associated with
      inhibitor development. We predicted the mean affinity for 10 major HLA class II
      alleles of wild-type FVIII-derived peptides that corresponded to 1456 reported
      cases of missense mutations. Linear regression analysis confirmed a significant
      association between the predicted mean peptide affinity and the mutation
      inhibitory status (P = 0.006). Significance was lost after adjustment on mutation
      position on FVIII domains. Although analysis of the A1-A2-A3-C1 domains yielded a
      positive correlation between predicted HLA-binding affinity and inhibitory status
      (OR = 0.29 [95% CI: 0.14-0.60] for the high affinity tertile, P = 0.002), the C2
      domain-restricted analysis indicated an inverse correlation (OR = 3.56 [1.10
      11.52], P = 0.03). Our data validate the importance of the affinity of FVIII
      peptides for HLA alleles to the immunogenicity of therapeutic FVIII in patients
      with missense mutations.

PMID- 24118515
TI  - Evaluation of falls by inpatients in an acute care hospital in Korea using the
      Morse Fall Scale.
AB  - The purpose of this study was to determine the cut-off values of the Korean
      version of the Morse Fall Scale (MFS-K) that would be most useful in identifying
      hospitalized patients at risk of falls in an acute-care setting in Korea. This
      study was conducted using the medical records of 66 patients who fell and 100
      patients who did not fall (no-fall patients) sampled from inpatients hospitalized
      at a tertiary acute-care hospital in Seoul during the period from 1 January to 30
      November 2009. The optimal cut-off point for the MFS-K was found to be 45 points,
      which produced an acceptable sensitivity and a fairly good specificity, negative
      predictive value and accuracy. The highest peak on the receiver operating
      characteristic curve was a cut-off score of 45 points in the MFS-K. Further
      research needs to be performed to determine the optimal cut-off score according
      to subjects' conditions through daily measurement with the MFS in medical or
      surgical patients who are relatively homogeneous in terms of individual and
      disease-related factors. 

PMID- 24118516
TI  - Editorial: Understanding of health economics among healthcare professionals.

PMID- 24118517
TI  - Psychometric testing of the properties of the spiritual health scale short form.
AB  - AIMS AND OBJECTIVES: To further examine the psychometric properties of the
      spiritual health scale short form, including its reliability and validity.
      BACKGROUND: Spirituality is one of the main factors associated with good health
      outcomes. A reliable and valid instrument to measure spirituality is essential to
      identify the spiritual needs of an individual and to evaluate the effect of
      spiritual care. DESIGN: A cross-sectional study design was used. METHODS: The
      study was conducted in six nursing schools in northern, central and southern
      Taiwan. The inclusion criterion for participants was nursing students with
      clinical practice experience. Initially, 1141 participants were recruited for the
      study, but 67 were absent and 48 did not complete the questionnaires. A total of
      1026 participants were finally recruited, indicating a response rate of 89.9%.
      The psychometric testing of the spiritual health scale short form included
      construct validity with confirmatory factor analysis, known-group validity and
      internal consistency reliability. RESULTS: The results of the confirmatory factor
      analysis supported the five-factor model as an acceptable model fit. In the known
      group validity, the results indicated that people who are in the category of
      primary religious affiliation have better spiritual health than people in the
      category of secondary religious affiliation and atheism. The result also
      indicated that the 24-item spiritual health scale short form achieved an
      acceptable internal consistency coefficient. CONCLUSIONS: The findings suggest
      that the spiritual health scale short form is a valid and reliable instrument for
      the appraisal of individual spiritual health. RELEVANCE TO CLINICAL PRACTICE: The
      spiritual health scale short form could provide useful information to guide
      clinical practice in assessing and managing people's spiritual health in Taiwan.

PMID- 24118518
TI  - The relationship between job satisfaction and intention to leave current
      employment among registered nurses in a teaching hospital.
AB  - AIMS AND OBJECTIVES: To assess Malaysian nurses' perceived job satisfaction and
      to determine whether any association exists between job satisfaction and
      intention to leave current employment. BACKGROUND: There is currently a shortage
      of qualified nurses, and healthcare organisations often face challenges in
      retaining trained nurses. Job satisfaction has been identified as a factor that
      influences nurse turnover. However, this has not been widely explored in
      Malaysia. DESIGN: Cross-sectional survey. METHODS: Registered nurses in a
      teaching hospital in Malaysia completed a self-administered questionnaire. Of the
      150 questionnaires distributed, 141 were returned (response rate = 94%). RESULTS:
      Overall, nurses had a moderate level of job satisfaction, with higher
      satisfaction for motivational factors. Significant effects were observed between
      job satisfaction and demographic variables. About 40% of the nurses intended to
      leave their current employment. Furthermore, age, work experience and nursing
      education had significant associations with intention to leave. Logistic
      regression analysis revealed that job satisfaction was a significant and
      independent predictor of nurses' intention to leave after controlling for
      demographic variables. CONCLUSION: The results suggest that there is a
      significant association between job satisfaction and nurses' intention to leave
      their current employment. It adds to the existing literature on the relationship
      between nurses' job satisfaction and intention to leave. RELEVANCE TO CLINICAL
      PRACTICE: Methods for enhancing nurses' job satisfaction are vital to promote the
      long-term retention of nurses within organisations. Attention must be paid to the
      needs of younger nurses, as they represent the majority of the nursing workforce
      and often have lower satisfaction and greater intention to leave than older
      nurses do. Strategies to nurture younger nurses, such as providing opportunities
      for further education, greater management decision-making capabilities and
      flexible working environment, are essential.

PMID- 24118519
TI  - Relational regulation theory and the role of social support and organisational
      fairness for nurses in a general acute context.
AB  - AIMS AND OBJECTIVES: To present a novel approach to nurse stress by exploring the
      demand-control-support model with organisational justice through the lens of
      relational regulation theory. BACKGROUND: Nursing is often stressful due to high
      demands and dissatisfaction with pay, which impacts the mental well-being and
      productivity of nurses. DESIGN: A cross-sectional design. METHODS: A validated
      questionnaire was sent to the work addresses of all nursing and midwifery staff
      in a medium-sized general acute hospital in Australia. A total of 190 nurses and
      midwives returned completed questionnaires for the analyses. RESULTS: The
      multiple regression analyses demonstrated that the model applies to the
      prototypical context of a general acute hospital and that job control, supervisor
      support and outside work support improve the job satisfaction and mental health
      of nurses. CONCLUSIONS: Most importantly, supervisor support was found to buffer
      the impact of excessive work demands. Fairness of procedures, distribution of
      resources and the quality and consistency of information are also beneficial.
      Relational regulation theory is applied to these findings as a novel way to
      conceptualise the mechanisms of support and fairness in nursing. RELEVANCE TO
      CLINICAL PRACTICE: The importance of nurses' well-being and job satisfaction is a
      priority for improving clinical outcomes. Practically, this means nurse managers
      should be encouraging nurses in the pursuit of diverse relational activities both
      at work and outside work.

PMID- 24118520
TI  - The qualitative findings from an online survey investigating nurses' perceptions
      of spirituality and spiritual care.
AB  - AIMS AND OBJECTIVES: To provide an opportunity for members to express their
      understandings of spirituality and spiritual care. BACKGROUND: The role and place
      of spirituality within nursing have been contested by academics and wider
      society. One argument posited is supporting patients with their spiritual needs
      is not the responsibility of nurses. This is despite a clear professional
      requirement for nurses to achieve competence in the delivery of spiritual care.
      DESIGN: The Royal College of Nursing (RCN) conducted an online survey of its
      membership to ascertain their perceptions of spirituality and spiritual care
      identifying current practice. METHODS: This article presents the findings from
      the final part of the survey that asked respondents to use a free-text facility
      to add comments on the subjects of spirituality and spiritual care. RESULTS:
      Overall, 4054 RCN members responded, of these 2327 provided additional comments.
      These comments were analysed using keyword and content/thematic analysis. Five
      broad themes emerged: (1) theoretical and conceptual understanding of
      spirituality, (2) fundamental aspects of nursing, (3) notion of integration and
      integrated care, (4) education and professional development and (5) religious
      belief and professional practice. Findings suggest that nurses have diverse
      understandings of spirituality and the majority consider spirituality to be an
      integral and fundamental element of the nurses' role. CONCLUSION: Generally,
      nurses had a broad, inclusive understanding of spirituality considering this to
      be 'universal'. There was some uncertainty and fear surrounding the boundaries
      between personal belief and professional practice. Respondents advocated formal
      integration of spirituality within programmes of nurse education. RELEVANCE TO
      CLINICAL NURSING: The concept of spirituality and the provision of spiritual care
      are now recognised as fundamental aspects of the nurse's role. There is a need
      for greater clarity between personal and professional boundaries to enable nurses
      to feel more confident and competent in delivering spiritual care.

PMID- 24118521
TI  - Perceptions of patients and nurses towards nurse caring behaviors in coronary
      care units in Jordan.
AB  - AIMS AND OBJECTIVES: To (1) identify the perceptions of Jordanian patients who
      suffer from coronary artery diseases towards nurse caring behaviours in critical
      care units; (2) identify the perceptions of Jordanian nurses who work in critical
      care units towards nurse caring behaviours; and (3) compare the perceptions of
      both patients and nurses towards nurse caring behaviours in critical care units.
      BACKGROUND: Caring is an important concept in nursing, when nursing behaviours
      were perceived by patients as caring behaviours, and thus, their satisfaction
      with the quality of care can be improved. Therefore, it is important for nurses
      to be knowledgeable about the caring behaviours as perceived by patients who
      complained from coronary artery diseases themselves. DESIGN: A descriptive
      comparative design was used. METHODS: A convenience sample of 150 patients who
      complained from coronary artery diseases and 60 critical care unit nurses
      completed the demographic form and the Caring Behavior Assessment scale. RESULTS:
      Patients in critical care units perceived physical and technical behaviours as
      most important caring behaviours, whereas nurses in critical care units perceived
      teaching behaviours as most important caring behaviours. CONCLUSION: There were
      significant differences between patient participants' and nurse participants'
      perceptions towards four subscales of Caring Behavior Assessment scale that
      should be considered when caring for patients with coronary artery diseases.
      RELEVANCE TO CLINICAL PRACTICE: Patients with coronary artery diseases need well
      trained and clinically competent nurses to meet their needs. 'Spiritual needs'
      was an important nurse caring behaviour that should be emphasised in nursing
      practice.

PMID- 24118522
TI  - Effect of spiritual intelligence, emotional intelligence, psychological ownership
      and burnout on caring behaviour of nurses: a cross-sectional study.
AB  - AIMS AND OBJECTIVES: To propose a model of prediction of caring behaviour among
      nurses that includes spiritual intelligence, emotional intelligence,
      psychological ownership and burnout. BACKGROUND: Caring behaviour of nurses
      contributes to the patients' satisfaction, well-being and subsequently to the
      performance of the healthcare organisations. This behaviour is influenced by
      physiological, psychological, sociocultural, developmental and spiritual factors.
      DESIGN: A cross-sectional survey was used, and data were analysed using
      descriptive statistics and structural equation modelling. METHODS: Data were
      collected between July-August 2011. A sample of 550 nurses in practice from seven
      public hospitals in and around Kuala Lumpur (Malaysia) completed the
      questionnaire that captured five constructs. Besides nurses, 348 patients from
      seven hospitals participated in the study and recorded their overall satisfaction
      with the hospital and the services provided by the nurses. Data were analysed
      using structural equation modelling (SEM). RESULTS: The key findings are: (1)
      spiritual intelligence influences emotional intelligence and psychological
      ownership, (2) emotional intelligence influences psychological ownership, burnout
      and caring behaviour of nurses, (3) psychological ownership influences burnout
      and caring behaviour of nurses, (4) burnout influences caring behaviour of
      nurses, (5) psychological ownership mediates the relationship between spiritual
      intelligence and caring behaviour and between emotional intelligence and caring
      behaviour of nurses and (6) burnout mediates the relationship between spiritual
      intelligence and caring behaviour and between psychological ownership and caring
      behaviour of nurses. CONCLUSIONS: Identifying the factors that affect caring
      behaviour of nurses is critical to improving the quality of patient care.
      Spiritual intelligence, emotional intelligence, psychological ownership and
      burnout of nurses play a significant role in effecting caring behaviour of
      nurses. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers must consider the
      relationships between these factors in their continuing care and incorporation of
      these in the nursing curricula and training.

PMID- 24118523
TI  - Striving for best practice: standardising New Zealand nursing procedures, 1930
      1960.
AB  - AIMS AND OBJECTIVES: To identify how nurses in the past determined best practice,
      using the context of New Zealand, 1930-1960. BACKGROUND: In the current context
      of evidence-based practice, nurses strive to provide the best care, based on
      clinical research. We cannot assume that nurses in the past, prior to the
      evidence-based practice movement, did not also have a deliberate process for
      pursuing best practice. Discovering historical approaches to determining best
      practice will enrich our understanding of how nurses' current efforts are part of
      a continuing commitment to ensuring quality care. DESIGN: Historical research.
      METHODS: The records of the Nursing Education Committee of the New Zealand
      Registered Nurses' Association, 1940-1959, and the 309 issues of New Zealand's
      nursing journal, Kai Tiaki, 1930-1960, were analysed to identify the profession's
      approach to ensuring best practice. This approach was then interpreted within the
      international context, particularly Canada and the USA. RESULTS: For nearly 30
      years, nurse leaders collaborated in undertaking national surveys of training
      hospitals requesting information on different nursing practices. They
      subsequently distributed instructions for a range of procedures and other aspects
      of nursing care to standardise practice. Standardising nursing care was an
      effective way to ensure quality nursing at a time when hospital care was
      delivered mostly by nurses in training. The reasons for and timing of
      standardisation of nursing care in New Zealand differed from the international
      move towards standardisation, particularly in the USA. CONCLUSIONS: Historically,
      nurses also pursued best practice, based on standardising nursing procedures.
      RELEVANCE TO CLINICAL PRACTICE: Examining the antecedents of the present evidence
      based approach to care reminds us that the process and reasons for determining
      best practice change through time. As knowledge and practice continually change,
      current confident assertions of best practice should and will continue to be
      challenged in future.

PMID- 24118524
TI  - 'The situation and the uncertainty about the coming result scared me but
      interaction with the radiographers helped me through': a qualitative study on
      patients' experiences of magnetic resonance imaging examinations.
AB  - AIMS AND OBJECTIVES: To describe patients' expectations before and experiences
      during a head-first magnetic resonance imaging scan. BACKGROUND: Previous studies
      have reported that patients experience fear and anxiety leading to discomfort
      before, during and after magnetic resonance imaging scans. Frequent problems
      persist in producing high-quality images due to motion artefacts. These results
      imply a need for improvement of patient conditions to allow for the added benefit
      of better diagnostic quality. Provision of extended written information has not
      appeared to reduce patients' stress, while interaction with staff has been
      described as the most important factor for reducing such feelings. DESIGN AND
      METHODS: A qualitative, phenomenological approach. Semi-structured interviews
      were conducted, and data were analysed with systematic text condensation.
      RESULTS: The experiences of the ten participants were encapsulated by the main
      theme: 'The situation and the uncertainty about the coming result scared me but
      interaction with the radiographers helped me through'. Subthemes were 'Prescan
      preparation', 'Mastering threats to self-control' and 'Personal achievements by
      completing the scan'. CONCLUSIONS: Our study has provided a deeper understanding
      of the expectations before, and experiences during, a head-first magnetic
      resonance imaging scan. Valuable insight into patients' apprehension about
      written and verbal information was obtained. The patients reported how they coped
      with the unfamiliar and stressful magnetic resonance imaging scanning procedure.
      A trustful dialogue with the radiographer was described as being crucial for
      patients' ability to manage fear, discomfort and feelings of loss of self
      control. We suggest a need for individualised information based on patient
      participation. RELEVANCE TO CLINICAL PRACTICE: Radiographers, as well as nurses
      caring for patients who will undergo magnetic resonance imaging examinations,
      should recognise the difficulties inherent in written information. It is also of
      importance to adjust the patient-radiographer interaction to address patients'
      expressions of worries about the scanning procedure or the following result.

PMID- 24118525
TI  - Increased in vitro fitness of multi- and extensively drug-resistant F15/LAM4/KZN
      strains of Mycobacterium tuberculosis.
AB  - The role of fitness in transmission of drug-resistant strains has been explored
      in previous studies; but has not been established for F15/LAM4/KZN strains, which
      were responsible for the extensively drug-resistant tuberculosis (XDR-TB)
      outbreak in Tugela Ferry, South Africa. The biological fitness of 15 clinical
      strains representing the F15/LAM4/KZN, Beijing, F11 and F28 families was
      determined by growth, viability and competition assays and correlated with DNA
      sequencing of eight genes associated with drug resistance and putative
      compensatory mechanisms. Similar growth rates were observed among susceptible,
      multidrug-resistant (MDR) and XDR strains of the KZN and F28 genotypes. In
      contrast, Beijing and F11 MDR strains demonstrated significantly reduced fitness.
      Resistant strains exhibited heterogeneous fitness profiles in competition with
      different susceptible strains, suggesting strain dependence. In addition, co
      culture growth rates were consistently higher than independent growth rates in
      13/14 competition pairs. All 14 drug-resistant strains retained viability, at a
      low CFU/mL, when paired with susceptible strains. The persistence of such
      resistant strains could consequently support the acquisition of additional drug
      resistance-conferring mutations and/or the evolution of compensatory mechanisms.
      Frequently occurring mutations were detected in KZN and F28 resistant strains
      whereas, the Beijing MDR strain harboured a less common katG mutation and the F11
      MDR strain had no katG mutation. Contrary to drug-resistant Beijing and F11
      strains, the successful transmission of KZN strains, particularly during the
      outbreak, may be attributed to the presence of drug-resistance-conferring
      mutations associated with little or no associated fitness costs. Amplified growth
      in co-culture may be suggestive of in vivo trans-complementation.

PMID- 24118526
TI  - High-risk human papillomavirus correlates with recurrence after laser ablation
      for treatment of patients with cervical intraepithelial neoplasia 3: a long-term
      follow-up retrospective study.
AB  - AIM: The purpose of our study was to evaluate the efficacy of laser ablation as a
      conservative treatment for cervical intraepithelial neoplasia 3 (CIN3) and assess
      whether the human papillomavirus (HPV) test is useful to predict recurrence after
      treatment. MATERIALS AND METHODS: A total of 134 patients who received laser
      ablation for treatment of CIN3 were enrolled in this study. During the follow-up
      period, patients were followed with cytological and colposcopic evaluations.
      Recurrence of CIN3 was regarded as the primary end-point. HPV genotype was tested
      before and after treatment. Post-treatment cumulative recurrence rates were
      estimated and comparisons by both patient age and HPV genotype were performed.
      RESULTS: Overall cumulative recurrence rate of CIN3 in the first year after
      treatment was 22.6% for all patients. No significant correlation was shown
      between patient age and recurrence. Patients infected by specific genotypes (16,
      18, 31, 33, 52, and 58) frequently failed to clear the infection after treatment.
      The 1-year recurrence-free survival in those positive after treatment for eight
      high-risk genotypes (16, 18, 31, 33, 35, 45, 52, and 58) was significantly lower
      (66.7%), compared to that in those positive for other high-risk types (78.6%).
      The recurrence-free survival of those who remained HPV-positive after treatment
      was significantly lower than those who turned negative. CONCLUSION: Laser
      ablation should be performed prudently with appropriate patient counseling about
      recurrence rate. Considering its minimal invasiveness, laser ablation is
      effective, especially for young patients who are negative for eight high-risk
      genotypes. With regard to HPV testing, although genotyping has significant value
      for predicting recurrence, screening for all genotypes warrants further
      evaluation.

PMID- 24118527
TI  - The specificity of acute and chronic microvascular alterations in renal
      allografts.
AB  - The diagnosis of an antibody-mediated rejection (AMR) is made when there is
      evident histologic injury in the presence of detectable donor-specific
      alloantibodies (DSA) and diffuse peritubular capillary C4d staining (C4d-pos). In
      the presence of only detectable DSA or C4d-pos, the tissue injury is currently
      considered "presumptive" for antibody causation. In acute antibody-mediated
      rejection (AAMR), diagnostic morphologic features include microvascular
      inflammation (MVI), specifically glomerulitis and peritubular capillaritis. In
      the case of chronic active AMR (CAAMR), these inflammatory lesions have
      progressed to chronic microvascular injury, transplant glomerulopathy (TG) and
      peritubular capillary basement membrane multilayering (PTCBMML). Either TG or
      PTCBMML is sufficient morphological evidence for a diagnosis of CAAMR.
      Unfortunately, these lesions are not specific. MVI, TG, and PTCBMML are found in
      the setting of cell-mediated immunity, as well as in association with non
      alloimmune mechanisms. The available treatments for AMR and CMR are different,
      and it is important to ascertain the dominant mechanism when approaching an
      individual patient. At present, no gold standard exists to establish the specific
      pathogenesis in the more ambiguous cases. We detail here the differential
      diagnosis of MVI, TG, and PTCBMML. 

PMID- 24118528
TI  - Increased risk of venous thromboembolism within the first year after
      Staphylococcus aureus bacteraemia: a nationwide observational matched cohort
      study.
AB  - OBJECTIVES: Recent evidence suggests that there is an association between
      infection and venous thromboembolism (VTE). Here, we examined the risk of VTE
      after Staphylococcus aureus bacteraemia (SAB) compared to the risk in control
      subjects. DESIGN AND SETTING: Register-based nationwide observational cohort
      study of hospitalized patients and matched control subjects from the general
      population in Denmark between 1995 and 2008. RESULTS: Amongst 15 669 SAB cases
      and 156 690 controls, 182 and 511, respectively, experienced VTE within 1 year.
      The overall incidence rate (IR) of VTE amongst cases was highest within the first
      30 days [IR of deep vein thrombosis (DVT), 39.3 (95% confidence interval (CI)
      28.9-53.4)/1000 person-years (PYs); IR of pulmonary embolism (PE), 16.3 (95% CI
      10.1-26.2)/1000 PYs]. IRs of DVT were particularly increased amongst cases with a
      previous diagnosis of VTE, community-acquired infection, a history of injection
      drug use and in younger age groups. The overall hazard ratio of VTE for cases
      compared to controls declined from 15.6 (95% CI 10.3-23.5) in the first 30 days
      after SAB to 4.5 (95% CI 3.2-6.2) from 181 to 365 days after infection. The
      increased risk of VTE amongst SAB patients persisted after excluding cases with
      identified VTE risk factors. CONCLUSIONS: There was a particularly high risk of
      VTE during the first month following an episode of SAB. The risk declined over
      time, but remained at a threefold increased level compared to control subjects,
      suggesting that there are shared risk factors for SAB and VTE. Patients with SAB
      and well-documented risk factors for VTE may benefit from thromboprophylaxis.

PMID- 24118530
TI  - How I do it: endovascular treatment of arteriovenous graft pseudoaneurysms-watch
      out for the mouth.
AB  - We present a case of arteriovenous graft pseudoaneurysms treated endovascularly
      with stent grafts and make suggestions regarding the technique of evaluating the
      pseudoaneurysms and choosing the proper location to deploy the stent grafts to
      maximize the outcomes and minimize the length of the graft covered by the stent.
      We also comment on the selection of lesions that are suitable to be treated with
      this technique. 

PMID- 24118529
TI  - p53 accumulation is a strong predictor of recurrence in estrogen receptor
      positive breast cancer patients treated with aromatase inhibitors.
AB  - Aromatase inhibitors have played a central role in endocrine therapy for estrogen
      receptor (ER)-positive breast cancer in postmenopausal women. However, factors
      predictive of the efficacy of aromatase inhibitors, and prognostic factors, both
      for early and late recurrence in women treated with adjuvant aromatase inhibitors
      have not been identified. Whole genome analysis identified that a TP53 gene
      mutation exists in ER-positive breast cancers, although the frequency of TP53
      gene mutation in luminal tumors is lower compared with basal-like or human
      epidermal growth factor receptor type 2 (HER2)-positive breast cancers. We
      examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki-67
      using immunohistochemistry in postmenopausal ER-positive breast cancer patients
      who were treated with aromatase inhibitors as adjuvant endocrine therapy. There
      were 53 (21%) tumors that contained 10% or more p53-positive cells. High p53
      expression was positively correlated with tumor grade, HER2 score and Ki-67
      expression. Significant association was observed between disease-free survival
      and high p53 expression in multivariate analysis (P < 0.0001). Compared with
      women without recurrence, women with early recurrence had significantly higher
      p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The
      present study demonstrates that p53 accumulation is a strong predictor of both
      early and late recurrence in ER-positive breast cancer patients treated with
      aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be
      a key biological characteristic of ER-positive breast cancer.

PMID- 24118531
TI  - Marked suppression of pulmonary vein firing after circumferential pulmonary vein
      isolation in patients with paroxysmal atrial fibrillation: is pulmonary vein
      firing an epiphenomenon?
AB  - INTRODUCTION: Rapid firing in pulmonary veins (PVs) is a leading cause of
      paroxysmal atrial fibrillation. We hypothesized that PV firing (PV-F) should
      continue after circumferential PV isolation (CPVI) because the PV tissue
      responsible for PV-F remains intact. METHODS AND RESULTS: In Group-1 (n = 92),
      isoproterenol (ISP) and adenosine triphosphate (ATP) were co-administered to
      provoke PV-F before and after CPVI. The site of rapid focal discharge that
      initiated atrial fibrillation (AF) defined PV-F versus non-PV-F. Additional 17
      patients with PV-F induced by ISP+ATP before CPVI were enrolled into Group-2 and
      various pacing maneuvers were used in conjunction to ISP+ATP to provoke PV-F
      after CPVI. In Group-1, AF was induced in 47/81 (58.0%) and 16/88 (18.2%)
      patients before and after CPVI, respectively (P < 0.01). Before CPVI, 43/47
      (91.5%) of the rapid firing originated from PV. After successful CPVI, 88/92
      patients were in sinus rhythm and non-PV-F was induced in 14/88 patients. PV-F
      was induced in 2/88 patients, which was eliminated by ganglionated plexus
      ablation outside the CPVI line. In Group-2, various pacing maneuvers with ISP+ATP
      only induced PV-F in 1/17 patients after CPVI. CONCLUSION: Marked suppression of
      PV-F after CPVI strongly suggests that the real source of PV-F is located in the
      atrium. PV-F may be an epiphenomenon.

PMID- 24118532
TI  - Relationship between jump landing kinematics and peak ACL force during a jump in
      downhill skiing: a simulation study.
AB  - Recent data highlight that competitive skiers face a high risk of injuries
      especially during off-balance jump landing maneuvers in downhill skiing. The
      purpose of the present study was to develop a musculo-skeletal modeling and
      simulation approach to investigate the cause-and-effect relationship between a
      perturbed landing position, i.e., joint angles and trunk orientation, and the
      peak force in the anterior cruciate ligament (ACL) during jump landing. A two
      dimensional musculo-skeletal model was developed and a baseline simulation was
      obtained reproducing measurement data of a reference landing movement. Based on
      the baseline simulation, a series of perturbed landing simulations (n = 1000) was
      generated. Multiple linear regression was performed to determine a relationship
      between peak ACL force and the perturbed landing posture. Increased backward
      lean, hip flexion, knee extension, and ankle dorsiflexion as well as an
      asymmetric position were related to higher peak ACL forces during jump landing.
      The orientation of the trunk of the skier was identified as the most important
      predictor accounting for 60% of the variance of the peak ACL force in the
      simulations. Teaching of tactical decisions and the inclusion of exercise
      regimens in ACL injury prevention programs to improve trunk control during
      landing motions in downhill skiing was concluded.

PMID- 24118533
TI  - Editorial Comment to Renal function after radical nephrectomy: development and
      validation of predictive models in Japanese patients.

PMID- 24118534
TI  - Combining animal personalities with transcriptomics resolves individual variation
      within a wild-type zebrafish population and identifies underpinning molecular
      differences in brain function.
AB  - Resolving phenotype variation within a population in response to environmental
      perturbation is central to understanding biological adaptation. Relating
      meaningful adaptive changes at the level of the transcriptome requires the
      identification of processes that have a functional significance for the
      individual. This remains a major objective towards understanding the complex
      interactions between environmental demand and an individual's capacity to respond
      to such demands. The interpretation of such interactions and the significance of
      biological variation between individuals from the same or different populations
      remain a difficult and under-addressed question. Here, we provide evidence that
      variation in gene expression between individuals in a zebrafish population can be
      partially resolved by a priori screening for animal personality and accounts for
      >9% of observed variation in the brain transcriptome. Proactive and reactive
      individuals within a wild-type population exhibit consistent behavioural
      responses over time and context that relates to underlying differences in
      regulated gene networks and predicted protein-protein interactions. These
      differences can be mapped to distinct regions of the brain and provide a
      foundation towards understanding the coordination of underpinning adaptive
      molecular events within populations. 

PMID- 24118535
TI  - Prevalence and risk factors of syphilis infection among female sex workers in
      Shenzhen, China: an observational study (2009-2012).
AB  - OBJECTIVE: To investigate prevalence and risk factors of syphilis infection among
      female sex workers (FSWs) in Shenzhen, China. METHODS: Observational study among
      (2009-2012) 1653 FSWs recruited by venue-based sampling using questionnaire-based
      interviews for socio-demographics, behaviours and syphilis testing results.
      Logistic regression was used to assess risk factors of syphilis infection.
      RESULTS: The overall syphilis prevalence was 4.7%, showing a slightly decreasing
      trend. Factors significantly associated with syphilis infection were inconsistent
      condom use (OR = 1.87, P = 0.015), illicit drug use (OR = 5.45, P < 0.001) and
      older age in years (OR = 1.08, P < 0.001). Venues where FSWs were recruited and
      duration of commercial sex work were not significantly associated with syphilis
      infection (P > 0.05). CONCLUSIONS: Syphilis is still common among FSWs in
      Shenzhen, China. Current comprehensive prevention programmes (e.g. condom
      promotion and peer education) should be continued to maintain and increase safe
      sexual practices and to reduce illicit drug use among FSWs. Expanding point-of
      care syphilis screening programmes may be an important strategy for early
      diagnosis. We recommend timely and effective treatment programmes to be linked to
      such screening programmes.

PMID- 24118536
TI  - Recommendations for post-mastectomy radiation therapy after neo-adjuvant
      chemotherapy: an International Survey of Radiation Oncologists.

PMID- 24118537
TI  - Asymmetrical fetal growth is not associated with altered trophoblast apoptotic
      activity in idiopathic intrauterine growth retardation.
AB  - AIM: To investigate whether there is difference in trophoblast apoptosis between
      infants with asymmetrical idiopathic intrauterine growth retardation (IUGR) and
      those with symmetrical fetal growth appropriate for gestational age (AGA).
      METHODS: Data and placentas from 52 singleton term pregnancies with idiopathic
      IUGR, from which a subgroup of 33 (63.4%) infants with asymmetrical growth and
      malnutrition was identified using the ponderal index served as a study group. The
      control group included 60 (86.9%) infants with symmetrical growth, identified by
      the same criterion among 69 normal singleton pregnancies with AGA. IUGR was
      defined by birthweight less than the 10th percentile of standard values. Ponderal
      index value was considered as the measurement of fetal growth proportionality.
      RESULTS: The proportion of fetal thinness up to ponderal index value was greater
      in the IUGR group than control (chi(2) = 9.2; P = 0.002). There was no
      statistically significant difference in the cytotrophoblast proliferation (t =
      0.88; P = 0.373), trophoblast expression of the Bcl-2 anti-apoptotic factor (z =
      0.66; P = 0.505), total trophoblast apoptotic index (t = 0.45; P = 0.651), as in
      cytotrophoblast (t = 0.01; P = 0.988) and syncytiotrophoblast apoptotic index (t
      = 0.34; P = 0.730) between the idiopathic asymmetrical IUGR and control group.
      CONCLUSION: Asymmetry of fetal growth is a result of rather long-term placental
      nutritive insufficiency in which trophoblasts have a central role. Although being
      crucial for its functioning, the proliferative and apoptotic trophoblast activity
      remains unaltered in the placentas from pregnancies with idiopathic IUGR and
      asymmetrical fetal growth. The results obtained in this study indicate that
      placental nutritive insufficiency may develop without any deviation in the
      physiological trophoblast regeneration via apoptosis.

PMID- 24118538
TI  - Safety of the yellow Fever vaccine: a retrospective study.
AB  - BACKGROUND: Yellow fever (YF) vaccine is considered safe; however, severe illness
      and death following vaccination have been reported. METHODS: Vaccine Safety
      Datalink (VSD) and US Department of Defense (DoD) data were used to identify
      adverse reactions following YF vaccination. Within the VSD, YF-vaccine-exposed
      subjects were compared to age-, site-, and gender-matched unexposed subjects. YF
      vaccine-exposed DoD subjects were studied using a risk-interval design. For both
      cohorts, ICD-9 codes were analyzed for allergic and local reactions, mild
      systemic reactions, and possible visceral and neurologic adverse events (AEs).
      RESULTS: The VSD cohort received 47,159 doses from 1991 through 2006. The DoD
      cohort received 1.12 million doses from 1999 through 2007. Most subjects received
      other vaccines simultaneously. In the VSD cohort, rates of allergic, local, and
      mild systemic reactions were not statistically different between YF-vaccine
      exposed and -unexposed subjects. In the DoD, there was an increased risk for
      outpatient allergic events in the period following vaccination with YF and other
      vaccines rate ratios [RR 3.85, 95% confidence interval (CI) 3.35-4.41] but with
      no increased risk for inpatient allergic reactions. In both cohorts, inpatient
      ICD-9 codes for visceral events were significantly less common following
      vaccination; inpatient codes for neurologic events were less common in the VSD YF
      vaccine-exposed adult cohort, but did not differ between exposed and unexposed
      periods in the DoD. In the DoD, one fatal case of YF-vaccine-associated
      viscerotropic disease (YF-vaccine-AVD) was detected. The estimated death rate was
      0.89 for 1,000,000 YF vaccine doses (95% CI 0.12-6.31/1,000,000 doses). No YF
      vaccine-associated deaths occurred in the VSD. CONCLUSIONS: In these closed
      cohorts we did not detect increased risk for visceral or neurologic events
      following YF vaccination. The death rate following YF vaccine was consistent with
      previous reports. These data support current recommendations for use of YF
      vaccine in young healthy individuals. These data are inadequate to judge safety
      of YF vaccines in elderly patients.

PMID- 24118539
TI  - Optimizing the trade-off between spatial and genetic sampling efforts in patchy
      populations: towards a better assessment of functional connectivity using an
      individual-based sampling scheme.
AB  - Genetic data are increasingly used in landscape ecology for the indirect
      assessment of functional connectivity, that is, the permeability of landscape to
      movements of organisms. Among available tools, matrix correlation analyses (e.g.
      Mantel tests or mixed models) are commonly used to test for the relationship
      between pairwise genetic distances and movement costs incurred by dispersing
      individuals. When organisms are spatially clustered, a population-based sampling
      scheme (PSS) is usually performed, so that a large number of genotypes can be
      used to compute pairwise genetic distances on the basis of allelic frequencies.
      Because of financial constraints, this kind of sampling scheme implies a drastic
      reduction in the number of sampled aggregates, thereby reducing sampling coverage
      at the landscape level. We used matrix correlation analyses on simulated and
      empirical genetic data sets to investigate the efficiency of an individual-based
      sampling scheme (ISS) in detecting isolation-by-distance and isolation-by-barrier
      patterns. Provided that pseudo-replication issues are taken into account (e.g.
      through restricted permutations in Mantel tests), we showed that the use of
      interindividual measures of genotypic dissimilarity may efficiently replace
      interpopulation measures of genetic differentiation: the sampling of only three
      or four individuals per aggregate may be sufficient to efficiently detect
      specific genetic patterns in most situations. The ISS proved to be a promising
      methodological alternative to the more conventional PSS, offering much
      flexibility in the spatial design of sampling schemes and ensuring an optimal
      representativeness of landscape heterogeneity in data, with few aggregates left
      unsampled. Each strategy offering specific advantages, a combined use of both
      sampling schemes is discussed. 

PMID- 24118540
TI  - Histological features of localized scleroderma 'en coup de sabre': a study of 16
      cases.
AB  - BACKGROUND: Early lesions of localized scleroderma are histologically
      characterized by perivascular lymphocytic infiltrate in the reticular dermis and
      swollen endothelial cells. However, there have been few information regarding
      histological features other than these findings in localized scleroderma.
      OBJECTIVE: Since en coup de sabre (ECDS) is a certain subset of localized
      scleroderma with a relatively uniform clinical manifestation, we focused on this
      disease subset and evaluated its histopathological features. METHODS: A total of
      16 patients with ECDS were retrospectively evaluated on the basis of clinical and
      histological findings. RESULTS: Regardless of clinical manifestations, vacuolar
      degeneration was found in all of the ECDS patients. Importantly, keratinocyte
      necroses were restricted to early and active ECDS lesions. In early ECDS patients
      (disease duration of <3 years), moderate to severe perivascular and/or
      periappendageal lymphocytic infiltrate and vacuolar changes in follicular
      epithelium were more prominent, whereas epidermal atrophy was less frequently
      observed, than in late ECDS patients (disease duration of >=6 years). CONCLUSION:
      Vacuolar degeneration at the dermoepidermal junction is a common histological
      feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate
      and vacuolar degeneration of follicular epithelium are characteristic especially
      in early ECDS, further supporting a canonical idea that the elimination of
      mutated epidermal cells by immune surveillance contributes to tissue damage and
      resultant fibrosis in localized scleroderma.

PMID- 24118541
TI  - Vitamin D levels after UVB radiation: effects by UVA additions in a randomized
      controlled trial.
AB  - BACKGROUND: Ultraviolet B (UVB) radiation increases the serum level of 25
      hydroxyvitamin D [25(OH)D]. However, the impact of UVA on vitamin D synthesis by
      UVB is poorly understood clinically. OBJECTIVE: To examine how different
      combinations of UVA and UVB radiation affect S-25(OH)D for the same vitamin D
      weighted exposure. MATERIALS AND METHODS: Healthy participants were recruited and
      subsequently divided into four comparable groups regarding initial 25(OH)D value.
      The different radiations given were whole-body UVB (n = 23), UVAB (n = 23) and
      UVA (n = 10). The controls (n = 19) had no intervention. The exposure times were
      chosen to give the same calculated vitamin D effective dose (suberythemal
      exposures <=1 standard erythema dose). Blood samples were collected before the
      first irradiation (t0), immediately after the last (fifth) irradiation (t1) and
      then after another 2 days after the last (fifth) irradiation (t2). RESULTS: UVB
      and UVAB radiation significantly increased 25(OH)D levels. In the UVA group the
      increase was less with the same vitamin D-weighted radiation dose. CONCLUSIONS:
      Short sessions of UVB or UVAB radiation with the same vitamin D-weighted exposure
      increased 25(OH)D levels. The UVA dose does not influence 25(OH)D levels under
      short exposure times. However, there was a significantly lower increase of
      25(OH)D levels during longer UVA irradiation (>=9 min).

PMID- 24118542
TI  - Treatment of subungual glomus tumors using the nail bed margin approach.
AB  - BACKGROUND: Subungual glomus tumors are rare soft-tissue tumors. The only
      effective treatment is complete surgical excision. Many surgical approaches had
      been reported to excise the tumor, but they all have limitations. OBJECTIVES: To
      evaluate the feasibility and efficacy of curing subungual glomus tumors using the
      nail bed margin approach. MATERIALS AND METHODS: From June 2005 to January 2012,
      17 patients diagnosed with subungual glomus tumors underwent complete excision
      using a nail bed margin approach under a surgical microscope. Recurrence of
      symptoms, local complications, and tumor recurrence were evaluated through long
      term follow-up. RESULTS: Histopathologic reports confirmed the diagnosis of
      glomus tumor in all patients. At a mean follow-up of 31.4 months, all patients
      had complete postoperative relief of pain, the nails recovered completely with
      normal shape, and no complications or recurrences were observed. CONCLUSION: In
      the treatment of subungual glomus tumors, the nail bed margin approach is a
      simple, feasible, effective new method with a low complication and recurrence
      rate. It can sufficiently expose and completely excise tumors at any subungual
      region. This approach is expected to be an excellent alternative approach for the
      excision of subungual glomus tumors.

PMID- 24118543
TI  - Being altered by the unexpected: understanding the perioperative patient's
      experience: a case study.
AB  - The present paper focuses on the process of understanding the patient in the
      context of perioperative caring and reports a story narrated by a perioperative
      nurse as well as her emerging understanding of the patient prior to surgery at an
      operating department. This qualitative case study had a dual purpose; firstly, to
      describe how the perioperative nurse's understanding of the patient emerged and,
      secondly, to establish how the researcher interpreted the situation. As a
      perioperative nurse and researcher, the author is both the narrator and
      interpreter. To date we have rarely discussed the fact that, in a perioperative
      context, the patient might feel ashamed of his/her body, even before arriving at
      the operating department. This new understanding emerged from the hermeneutical
      dialogue in the present study. 

PMID- 24118545
TI  - Panencephalopathic Creutzfeldt-Jakob disease with distinct pattern of prion
      protein deposition in a patient with D178N mutation and homozygosity for valine
      at codon 129 of the prion protein Gene.
AB  - Prion diseases include sporadic, acquired and genetic forms linked to mutations
      of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP
      mutation, distinct phenotypes can be observed, depending on the methionine/valine
      codon 129 polymorphism. We present here a 53-year-old woman with D178N mutation
      in the PRNP gene and homozygosity for valine at codon 129. The disease started at
      age 47 with memory deficits, progressive cognitive impairment and ataxia. The
      clinical picture slowly worsened to a state of akinetic mutism in about 2 years
      and the disease course was 6 years. The neuropathologic examination demonstrated
      severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin
      loss and tissue rarefaction in the hemispheric white matter, configuring
      panencephalopathic Creutzfeldt-Jakob disease. PrP deposition was present in the
      cerebral cortex, basal ganglia and cerebellum with diffuse synaptic-type pattern
      of immunoreactivity and clusters of countless, small PrP deposits, particularly
      evident in the lower cortical layers, in the striatum and in the molecular layer
      of the cerebellum. Western blot analysis showed the presence of type 1 PrP(Sc)
      (Parchi classification). These findings underline the clear-cut distinction
      between the neuropathological features of Creutzfeldt-Jakob disease associated
      with D178N PRNP mutation and those of fatal familial insomnia. 

PMID- 24118544
TI  - GfsA encodes a novel galactofuranosyltransferase involved in biosynthesis of
      galactofuranose antigen of O-glycan in Aspergillus nidulans and Aspergillus
      fumigatus.
AB  - The cells walls of filamentous fungi in the genus Aspergillus have
      galactofuranose (Galf)-containing polysaccharides and glycoconjugates, including
      O-glycans, N-glycans, fungal-type galactomannan and
      glycosylinositolphosphoceramide, which are important for cell wall integrity.
      Here, we attempted to identify galactofuranosyltransferases that couple Galf
      monomers onto other wall components in Aspergillus nidulans. Using reverse
      genetic and biochemical approaches, we identified that the AN8677 gene encoded a
      galactofuranosyltransferase, which we called GfsA, involved in Galf antigen
      biosynthesis. Disruption of gfsA reduced binding of beta-Galf-specific antibody
      EB-A2 to O-glycosylated WscA protein and galactomannoproteins. The results of an
      in-vitro Galf antigen synthase assay revealed that GfsA has beta1,5- or beta1,6
      galactofuranosyltransferase activity for O-glycans in glycoproteins, uses UDP-d
      Galf as a sugar donor, and requires a divalent manganese cation for activity.
      GfsA was found to be localized at the Golgi apparatus based on cellular
      fractionation experiments. DeltagfsA cells exhibited an abnormal morphology
      characterized by poor hyphal extension, hyphal curvature and limited formation of
      conidia. Several gfsA orthologues were identified in members of the
      Pezizomycotina subphylum of Ascomycota, including the human pathogen Aspergillus
      fumigatus. To our knowledge, this is the first characterization of a fungal beta
      galactofuranosyltransferase, which was shown to be involved in Galf antigen
      biosynthesis of O-glycans in the Golgi.

PMID- 24118546
TI  - Comparison between noncontrast computed tomography and magnetic resonance imaging
      for detection and characterization of thoracolumbar myelopathy caused by
      intervertebral disk herniation in dogs.
AB  - Magnetic resonance imaging (MRI) and computed tomography (CT) are commonly used
      to evaluate dogs with thoracolumbar myelopathy; however, relative diagnostic
      sensitivities for these two modalities have not been previously reported. The
      purpose of this prospective study was to compare diagnostic sensitivity and
      observer agreement for MRI and CT in a group of dogs with thoracolumbar
      myelopathy due to surgically confirmed intervertebral disk herniation (IVDH). All
      included dogs had magnetic resonance (MR) imaging followed by noncontrast CT
      using standardized protocols. Three experienced observers interpreted each
      imaging study independently without knowledge of clinical or surgical findings.
      The operating surgeon was aware of MR findings but not CT findings at the time
      surgical findings were recorded. Forty-four dogs met the inclusion criteria. The
      sensitivity of CT was 88.6% (79.5%-94.2%) and of MR was 98.5% (95% confidence
      interval, 94.1%-99.7%) for diagnosis of intervertebral disk herniation.
      Specificity was not calculated, as all dogs had IVDH at surgery. Magnetic
      resonance imaging was more accurate than CT for identifying the site of
      intervertebral disk herniation-associated spinal cord compression and
      differentiating disk extrusion vs. protrusion. Computed tomography was less
      accurate for lesion localization in per acute cases, as well as for
      chondrodystrophic, female, older and smaller (<7 kg) dogs. Inter-rater agreement
      was good for lesion lateralization for both MR and CT (kappa = 0.687, 95% CI =
      0.552, 0.822, P = 0.002, and kappa = 0.692, 95% CI = 0.542, 0.842, P = 0.003).
      Findings from the current study indicated that MR imaging was more sensitive and
      accurate than noncontrast CT for diagnosis and characterization of thoracolumbar
      myelopathy due to IVDH in dogs. 

PMID- 24118547
TI  - Addition of thalidomide to melphalan and prednisone treatment prolongs survival
      in multiple myeloma--a retrospective population based study of 1162 patients.
AB  - The combination of melphalan and prednisone (MP) has been the standard treatment
      of multiple myeloma (MM). Since the introduction of novel agents, the clinical
      outcome in MM has improved. Six randomized prospective studies with thalidomide
      combined with melphalan and prednisone (MPT) compared to MP have been performed,
      most of them showing that MPT gives a better response rate and median overall
      survival (OS). Amongst 1843 MM patients admitted to 15 Swedish centres, we
      selected all patients treated with MP and MPT in first, second, third or fourth
      line of therapy, in total 888 patients treated with MP and 274 with MPT. Patients
      were evaluated for response rate, OS and Time to Next Treatment. Multivariate Cox
      model analysis was made to adjust for different criteria at time for MM
      diagnosis. The median OS from beginning of first line of treatment was 2.2/4.2
      yrs after MP/MPT respectively, and in second, third and fourth line of treatment
      1.8/2.9, 1.4/1.6 and 1.1/1.9 yrs (P < 0.0001, 0.003, 0.74 and 0.235). The
      relative risk for death in the MPT group vs. the MP group was 0.61 (95% CI: 0.45
      0.84) in first and 0.55 (0.38-0.83), P < 0.01) in second line. Treatment with MPT
      gave a significantly better OS rate after both first and second line of therapy
      when compared with treatment with MP only. 

PMID- 24118548
TI  - Issues in the ageing individual with haemophilia and other inherited bleeding
      disorders: understanding and responding to the patients' perspective.
AB  - An increasing number of individuals with haemophilia and other severe bleeding
      disorders who are >=40 years of age are entering uncharted territory with respect
      to the identification and management of medical, physical and social issues
      relevant to ageing with a bleeding disorder. This is because the population
      experienced considerable mortality during the HIV/AIDs and hepatitis C epidemic
      due to exposure to tainted blood products for treatment of bleeding. As a result,
      few older individuals with this disorder survive today. To provide insight for
      how the comprehensive care team can adapt to the changing needs of the adult
      haemophiliac we evaluated the patient perspective. The objective of this study
      was to identify key themes of importance in the ageing population with
      haemophilia and other inherited bleeding disorders. For this study all subjects
      with a diagnosis of haemophilia A or B, von Willebrand disease or rare bleeding
      disorders 40 years or older from a single clinic were invited to participate.
      Audio-recordings of groups of six to eight participants were conducted by an
      independent investigator without content expertise. Transcripts were analysed
      using N*vivo (v. 8) software using thematic content analysis. Overall, 32
      subjects, 18 men/14 women, with a mean age of 57.5 years (median 56.0 years) and
      range of 40-77 years, participated. Three major themes emerged: (i) reflection on
      living an active life, (ii) 'normal' ageing vs. disease-specific impacts and
      (iii) the health system, and its ability to respond to their needs as ageing
      individuals with bleeding disorders. We found some anticipated themes and some
      unexpected ones, confirming that true perspective can only be provided by the
      patients themselves. Knowledge of these important themes has informed the
      development of new programmes aimed at this growing segment of the patient
      population.

PMID- 24118549
TI  - A comprehensive analysis of dyslipidaemia management in a large health care
      system.
AB  - RATIONALE, AIMS AND OBJECTIVES: Dyslipidaemia is a cardiovascular risk factor,
      and national screening and treatment guidelines have been established, but
      achievement of these remains inadequate. Multidisciplinary approaches, such as
      the chronic care model, have been applied to other chronic diseases and likely
      would be applicable to the management of dyslipidaemia. We therefore aimed to
      comprehensively study the different components of a multidisciplinary management
      approach to dyslipidaemia in a large health care system for patients at a high
      risk for cardiovascular events. METHODS: All patients at a Veterans Affairs
      Medical Center in the United States over 3 years with diabetes and/or coronary
      artery disease were included. Various clinical and demographic variables were
      collected and achievement of national cholesterol goals was determined.
      Univariate and multivariate analyses were conducted to determine the association
      of different health care variables with improved patient cholesterol guideline
      achievement. RESULTS: There were 3559 patients in the study population and 51.0%
      had achieved national cholesterol goals. Multivariate analyses showed that
      patients who had achieved goals were more likely to have attended cardiology
      clinic [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.3-2.01] and
      nutrition clinic (OR = 1.3, 95% CI = 1.04-1.7) and were more likely to have
      primary care providers who were nurse practitioners (OR = 1.6, 95% CI = 1.2-2.0),
      practicing full-time (OR = 1.8, 95% CI = 1.5-2.1) and at the main hospital-based
      clinics (OR = 1.5, 95% CI = 1.3-1.9). CONCLUSIONS: Our study identifies different
      components of a multidisciplinary approach to management of dyslipidaemia that
      are efficacious and these results may help guide future investment in this area.

PMID- 24118550
TI  - Pretransplant identification of acute rejection risk following kidney
      transplantation.
AB  - Lack of an accepted definition for 'high immunological risk' hampers
      individualization of immunosuppressive therapy after kidney transplantation. For
      recipient-related risk factors for acute rejection, the most compelling evidence
      points to younger age and African American ethnicity. Recipient gender, body
      mass, previous transplantation, and concomitant infection or disease do not
      appear to be influential. Deceased donation now has only a minor effect on
      rejection risk, but older donor age remains a significant predictor. Conventional
      immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant
      anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in
      light of growing understanding about the role of donor-specific antibodies (DSA).
      At the time of transplant, delayed graft function is one of the most clear-cut
      risk factors for acute rejection. Extended cold ischemia time (>= 24 h) may also
      play a contributory role. While it is not yet possible to establish conclusively
      the relative contribution of different risk factors for acute rejection after
      kidney transplantation, the available data point to variables that should be
      taken into account at the time of transplant. Together, these offer a realistic
      basis for planning an appropriate immunosuppression regimen in individual
      patients.

PMID- 24118551
TI  - Phosphorylation of the N- and C-terminal UPF1 domains plays a critical role in
      plant nonsense-mediated mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is an essential quality control system that
      degrades aberrant transcripts containing premature termination codons and
      regulates the expression of several normal transcripts. Targets for NMD are
      selected during translational termination. If termination is slow, the UPF1 NMD
      factor binds the eRF3 protein of the termination complex and then recruits UPF2
      and UPF3. Consequently, the UPF1-2-3 NMD complex induces SMG7-mediated
      degradation of the target mRNA. It is unknown how formation of the NMD complex
      and transcript degradation are linked in plants. Previously we have shown that
      the N- and C-terminal domains of UPF1 act redundantly and that the N-terminal
      domain is phosphorylated. To clarify the role of UPF1 phosphorylation in plant
      NMD, we generated UPF1 mutants and analyzed their phosphorylation status and the
      NMD competency of the mutants. We show that although several residues in the N
      terminal domain of UPF1 are phosphorylated, only three phosphorylated amino
      acids, S3, S13 and T29, play a role in NMD. Moreover, we found that the C
      terminal domain consists of redundant S/TQ-rich segments and that S1076 is
      involved in NMD. All NMD-relevant phosphorylation sites were in the S/TQ context.
      Co-localization and fluorescence resonance energy transfer-fluorescence lifetime
      imaging assays suggest that N-terminal and probably also C-terminal
      phosphorylated S/TQ residues are the binding platform for SMG7. Our data support
      the hypothesis that phosphorylation of UPF1 connects NMD complex formation and
      the SMG7-mediated target transcript degradation steps of NMD. SMG7 binds the
      phosphorylated S/TQ sites of the UPF1 component of the NMD complex, and then it
      induces the degradation of the NMD target. 

PMID- 24118552
TI  - Adaptation and constraint in a stickleback radiation.
AB  - The evolution of threespine sticklebacks in freshwater lakes constitutes a well
      studied example of a phenotypic radiation that has produced numerous instances of
      parallel evolution, but the exact selective agents that drive these changes are
      not yet fully understood. We present a comparative study across 74 freshwater
      populations of threespine stickleback in Norway to test whether evolutionary
      changes in stickleback morphology are consistent with adaptations to physical
      parameters such as lake depth, lake area, lake perimeter and shoreline
      complexity, variables thought to reflect different habitats and feeding niches.
      Only weak indications of adaptation were found. Instead, populations seem to have
      diversified in phenotypic directions consistent with allometric scaling
      relationships. This indicates that evolutionary constraints may have played a
      role in structuring phenotypic variation across freshwater populations of
      stickleback. We also tested whether the number of lateral plates evolved in
      response to lake calcium levels, but found no evidence for this hypothesis. 

PMID- 24118553
TI  - Epidemiology of Group B streptococcus isolated from pregnant women in Beijing,
      China.
AB  - Group B Streptococcus (GBS) was the main causative organism of invasive
      infections in newborns due to vertical transmission from the colonized mothers.
      The study was undertaken to determine colonization rate, serotype distribution,
      genotypic characterization, antibiotic susceptibility profiles and molecular
      characteristics of erythromycin-resistant strains of GBS in pregnant women in
      Beijing, China. Vaginal-rectal swabs were collected from a total of 2850 pregnant
      women at 35-37 weeks of gestation, in which 7.1% were GBS positive. Serotypes
      III, Ia and V predominated. All isolates were penicillin susceptible, whereas the
      resistance rates for erythromycin and clindamycin were strikingly high.

PMID- 24118554
TI  - Outcome and development of symptoms after orthotopic liver transplantation for
      Wilson disease.
AB  - BACKGROUND: Wilson disease (WD) is an autosomal recessive copper storage disease
      resulting in hepatic and neurologic dysfunction. Liver transplantation is an
      effective treatment for fulminant cases for patients with chronic liver disease.
      Reports on the outcome of neuropsychiatric symptoms after orthotopic liver
      transplantation (OLT) are limited. AIM: To assess the course of neuropsychiatric
      and hepatic symptoms after liver transplantation for Wilson disease METHODS:
      Nineteen patients with Wilson disease received liver transplantation and were
      followed prospectively from 2005 to 2010 for the development of hepatic,
      neurological and psychiatric symptoms. RESULTS: Eight patients (all female) were
      transplanted for acute liver failure and eleven patients for chronic liver
      failure. Patient survival rates one and five yr after transplantation were 78%
      and 65%, respectively. Of the surviving patients, hepatic symptom scores improved
      in all patients and neurological symptom scores improved in all but one patient
      after OLT compared to the time of initial diagnosis and compared to pre-OLT
      status. Psychiatric symptoms showed moderate improvements. CONCLUSION: Survival
      after OLT for Wilson disease with end-stage liver disease is excellent. Overall,
      neuropsychiatric symptoms improved after transplantation, substantiating
      arguments for widening of the indication for liver transplantation in symptomatic
      neurologic Wilson disease patients with stable liver function.

PMID- 24118555
TI  - Anterior urethral valves without diverticulae: a report of two cases and a review
      of the literature.
AB  - Two unusual cases of anterior urethral valves (AUV) without diverticulae are
      presented. The first case is a male child born with prenatal diagnosis of
      bilateral hydronephrosis. On cystoscopy, iris-like diaphragm valves were
      encountered about 3 mm distal to the skeletal sphincter. In the second case, an
      18-month-old male child was investigated for recurrent febrile urinary tract
      infections and obstructed urinary symptoms. Cystoscopy confirmed the presence of
      slit-like valves 5 mm distal to the skeletal sphincter. Fulguration of the AUVs
      was performed in both cases. It may be worthwhile to review all cases of anterior
      urethral obstruction collectively and re-categorize them appropriately to include
      the unusual AUVs without diverticulum in that classification. 

PMID- 24118556
TI  - Registered nurses' reflections on discussing sexuality with patients:
      responsibilities, doubts and fears.
AB  - AIMS AND OBJECTIVES: To describe registered nurses' reflections on discussing
      sexuality with patients. BACKGROUND: It is known that many diseases and
      treatments have a negative impact on sexual health. Despite these facts,
      registered nurses typically do not address sexual issues with patients. DESIGN: A
      descriptive design and a qualitative approach were used. METHODS: Interviews were
      conducted in 2010 with 10 registered nurses. The data were analysed using
      qualitative content analysis. RESULTS: The themes 'Doing the right thing and
      doing good', 'Could've, would've, should've: a nurse's conflicting feelings' and
      'I just don't talk about it: sexuality as a nontopic' confirmed the notion that
      discussing sexuality in nursing care is still challenging and difficult for
      nurses, but also revealed that nurses who do talk to patients about sexual issues
      do so based on their strong sense of wanting to help. They felt a responsibility
      because of their knowledge in the area, but the topic also brought out
      conflicting feelings such as fear and embarrassment. Lack of time, support and
      places to talk to patients in private as well as prejudice were contributing
      factors to their not addressing sexuality. Some nurses also felt that sexuality
      was someone else's responsibility and a taboo subject. CONCLUSIONS: Patients'
      sexuality is still surrounded by silence. But factors exist that can facilitate
      discussion of sexuality. Nurses have a key role in detecting ill-health. This
      study suggests that when nurses use their knowledge and go beyond their comfort
      zone and address sexuality, they can identify patients' sexual problems.
      RELEVANCE TO CLINICAL PRACTICE: Nurses need to understand how their knowledge can
      help patients who are experiencing sexual problems; they also need support from
      the workplace and to have access to routines that reinforce the notion that
      sexuality is a topic worth discussing.

PMID- 24118557
TI  - Cost and robotic surgery in gynecology.
AB  - Since the introduction of robotic technology, there have been significant changes
      to the field of gynecology. The number of minimally invasive procedures has
      drastically increased, with robotic procedures rising remarkably. To date several
      authors have published cost analyses demonstrating that robotic hysterectomy for
      benign and oncologic indications is more costly compared to the laparoscopic
      approach. Despite being more expensive than laparoscopy, other studies have found
      robotics to be less expensive and more effective than laparotomy. In this review,
      controversies surrounding cost-effectiveness studies are explored. 

PMID- 24118558
TI  - hERG inhibitors with similar potency but different binding kinetics do not pose
      the same proarrhythmic risk: implications for drug safety assessment.
AB  - INTRODUCTION: Since the discovery of the link that exists between drug-induced
      hERG inhibition and Torsade de Pointes (TdP), extreme attention has been given to
      avoid new drugs inhibiting this channel. hERG inhibition is routinely screened
      for in new drugs and, typically, IC50 values are compared to projected plasma
      concentrations to define a safety margin. METHODS AND RESULTS: We aimed to show
      that drugs with similar hERG potency are not uniformly pro-arrhythmic-this
      depends on the drug binding kinetics and mode of action (trapped or not) rather
      than the IC50 value only. We used a mathematical model of hERG and its related
      encoded current IKr to simulate drug binding in different configurations.
      Expression systems mimicking the screening process were first investigated. hERG
      model was then incorporated into a canine action potential (AP) and tissue model
      to study the impact of drug binding configurations on AP and pseudo-ECG (QT
      interval prolongation). Our data show that: (1) trapped and not trapped
      configurations and different binding kinetics could be identified during hERG
      screening; (2) slow binding, not trapped drugs, induced less AP prolongation and
      minimal QT interval prolongation (4.7%) at a concentration equal to the IC50
      whereas maximal pro-arrhythmic risk was observed for trapped drugs at the same
      concentration (QT interval prolongation, 23.1%). CONCLUSION: Our study
      demonstrates the need for screening for hERG binding configurations rather than
      potency alone. It also demonstrates the potential link between hERG, drug mode of
      action and TdP, and the need to question the current regulatory guidance.

PMID- 24118559
TI  - Influence of age, disease onset and ApoE4 on visual medial temporal lobe atrophy
      cut-offs.
AB  - BACKGROUND: Visual assessment of medial temporal lobe atrophy (MTA; range 0-4,
      from no atrophy to increasing atrophy of the choroid fissure, temporal horns and
      hippocampus) is a sensitive radiological marker of Alzheimer's disease (AD). One
      of the critical elements for visual MTA assessment is the cut-off score that
      determines deviation from normality. METHODS: In this study, we assessed the
      sensitivity and specificity of different MTA cut-off scores to classify control
      subjects, individuals with mild cognitive impairment (MCI) and AD patients from
      two large independent cohorts, AddNeuroMed and Alzheimer's Disease Neuroimaging
      Initiative. Of note, we evaluated the effects of clinical, demographic and
      genetic variables on the classification performance according to the different
      cut-offs. RESULTS: A cut-off of >=1.5 based on the mean MTA scores of both
      hemispheres showed higher sensitivity in classifying patients with AD (84.5%) and
      MCI subjects (75.8%) who converted to dementia compared to an age-dependent cut
      off. The age-dependent cut-off showed higher specificity or ability to correctly
      identify control subjects (83.2%) and those with MCI who remained stable (65.5%).
      Increasing age, early-onset disease and absence of the ApoE epsilon4 allele had a
      stronger influence on classifications using the >=1.5 cut-off. Above 75 years of
      age, an alternative cut-off of >=2.0 should be applied to achieve a
      classification accuracy for both patients with AD and control subjects that is
      clinically useful. CONCLUSION: Clinical, demographic and genetic variables can
      influence the classification of MTA cut-off scores, leading to misdiagnosis in
      some cases. These variables, in addition to the differential sensitivity and
      specificity of each cut-off, should be carefully considered when performing
      visual MTA assessment.

PMID- 24118561
TI  - A program to support self-efficacy among athletes.
AB  - The objective of this study is to evaluate the effectiveness of a proprietary
      program for increasing self-efficacy among track and field athletes through
      vicarious experience and successful control over excitation and to determine the
      changes in the cognitive dimensions related to self-efficacy: dispositional
      optimism, hope of success and locus of control. An experimental two-group design
      with a pre-test and a post-test in the experimental and control groups was used.
      Forty-two athletes (29 women and 13 men) aged 17 to 24 years randomly assigned to
      the intervention and control groups took part in the study. The General Scale of
      Self-Efficacy, Hope for Success Questionnaire, Life Orientation Test Revised, and
      Internal-External Locus of Control Scale were used. The study's results indicate
      that the program was effective. Participants in the intervention group
      demonstrated a substantial increase in self-efficacy (P = 0.001). This was not
      observed in the control group (P = 0.732). After the completion of the program,
      athletes in the intervention group had significantly higher levels of self
      efficacy (P = 0.001) and optimism (P = 0.017). They also had more internal locus
      of control compared to the control group (P = 0.001). Contrary to expectations,
      athletes in the intervention group demonstrated a substantially lower level of
      propensity in pathways (P = 0.001) as well as in agency (P = 0.001) (both
      components of the hope for success).

PMID- 24118560
TI  - Comparison of population genetic patterns in two widespread freshwater mussels
      with contrasting life histories in western North America.
AB  - We investigate population genetic structuring in Margaritifera falcata, a
      freshwater mussel native to western North America, across the majority of its
      geographical range. We find shallow rangewide genetic structure, strong
      population-level structuring and very low population diversity in this species,
      using both mitochondrial sequence and nuclear microsatellite data. We contrast
      these patterns with previous findings in another freshwater mussel species group
      (Anodonta californiensis/A. nuttalliana) occupying the same continental region
      and many of the same watersheds. We conclude that differences are likely caused
      by contrasting life history attributes between genera, particularly host fish
      requirements and hermaphroditism. Further, we demonstrate the occurrence of a
      'hotspot' for genetic diversity in both groups of mussels, occurring in the
      vicinity of the lower Columbia River drainage. We suggest that stream hierarchy
      may be responsible for this pattern and may produce similar patterns in other
      widespread freshwater species. 

PMID- 24118562
TI  - The effect of buttonhole cannulation vs. rope-ladder technique on hemodialysis
      access patency.
AB  - The rope-ladder (RL) technique is the most common technique used for cannulation
      of arteriovenous fistulae (AVF). Buttonhole cannulation (BHC), or constant-site
      technique, is recommended by the National Kidney Foundation's Kidney Disease
      Outcome Quality Initiative (NKF/KDOQI) vascular access guidelines. We compared
      outcomes of primary patency, episodes of bacteremia, access blood flow (Qa), and
      quality of life (QoL) scores between RL and BHC patients. Using a prospectively
      collected, vascular access database, a total of 45 prevalent dialysis patients
      using BHC were compared with 38 patients using the RL technique over a median of
      12 months (inter-quartile range: 4-27 months). The two groups did not differ
      significantly in demographics except that diabetes was more common in those using
      BHC as compared to rope-ladder (69% vs. 34%; p = 0.002). Risk factors associated
      with lack of primary patency were age (hazards ratio [HR] = 1.02 per decade; 95%
      CI: 1.00-1.03; p = 0.04) and female gender (HR = 1.92; 95% CI: 1.08-3.40; p =
      0.03). Use of the buttonhole technique was not associated with improved primary
      patency (HR = 1.22, 95% CI: 0.65-2.28; p = 0.53). Episodes of bacteremia and mean
      scores from KDQOL-36 did not differ significantly between the groups. This study
      demonstrates for the first time that BHC use is not associated with improved
      access patency. 

PMID- 24118563
TI  - Multiple sessions of transcranial direct current stimulation to the intact
      hemisphere improves visual function after unilateral ablation of visual cortex.
AB  - Damage to cerebral systems is frequently followed by the emergence of
      compensatory mechanisms, which serve to reduce the effects of brain damage and
      allow recovery of function. Intrinsic recovery, however, is rarely complete. Non
      invasive brain stimulation technologies have the potential to actively shape
      neural circuits and enhance recovery from brain damage. In this study, a stable
      deficit for detecting and orienting to visual stimuli presented in the
      contralesional visual hemifield was generated by producing unilateral brain
      damage of the right posterior parietal and contiguous visual cortical areas. A
      long regimen of inhibitory non-invasive transcranial direct-current stimulation
      (cathodal tDCS, 2 mA, 20 min) was applied to the contralateral (intact) posterior
      parietal cortex over 14 weeks (total of 70 sessions, one per day, 5 days per
      week) and behavioral outcomes were periodically assessed. In three out of four
      stimulated cats, lasting recovery of visuospatial function was observed. Recovery
      started after 2-3 weeks of stimulation, and recovered targets were located first
      in the periphery, and moved to more central visual field locations with the
      accrual of stimulation sessions. Recovery for moving tasks followed a biphasic
      pattern before reaching plateau levels. Recovery did not occur for more difficult
      visual tasks. These findings highlight the ability of multiple sessions of
      transcranial direct-current stimulation to produce recovery of visuospatial
      function after unilateral brain damage. 

PMID- 24118564
TI  - Lactobacillus rhamnosus protects human colonic muscle from pathogen
      lipopolysaccharide-induced damage.
AB  - BACKGROUND: Lactobacillus species might positively affect gastrointestinal
      motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that
      elicits anti-inflammatory activity and exerts protective effects on damage
      induced by lipopolysaccharide (LPS). Whether such effect occurs in
      gastrointestinal smooth muscle has not been established yet. Aim of this study
      was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of
      supernatants harvested from LGG cultures on human colonic smooth muscle and to
      explore their protective activity against LPS-induced myogenic morpho-functional
      alterations. METHODS: The effects of LGG (ATCC 53103 strain) and of supernatants
      have been tested on both human colonic smooth muscle strips and isolated cells in
      the absence or presence of LPS obtained from a pathogenic strain of Escherichia
      coli. Their effects on myogenic morpho-functional properties, on LPS-induced
      NFkappaB activation, and on cytokine production have been evaluated. Toll-like
      receptor 2 expression has been analyzed by qPCR and flow cytometry. KEY RESULTS:
      Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it
      was capable of activating an intrinsic myogenic response counteracting LPS
      induced alterations. In particular, both LGG and supernatants significantly
      reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell
      shortening and inhibition of contractile response. They also hindered LPS-induced
      pro-inflammatory effects by decreasing pro-inflammatory transcription factor
      NFkappaB activation and pro-inflammatory cytokine IL-6 secretion, and restored
      the secretion levels of anti-inflammatory cytokine IL10. CONCLUSIONS &
      INFERENCES: Taken together these data demonstrate that LGG protects human colonic
      smooth muscle from LPS-induced myogenic damage and might be beneficial on
      intestinal motor disorders due to bacterial infection.

PMID- 24118565
TI  - Counselling on and women's awareness of pregnancy danger signs in selected rural
      health facilities in Burkina Faso, Ghana and Tanzania.
AB  - OBJECTIVE: The aims of this study were to (i) assess healthcare workers'
      counselling practices concerning danger signs during antenatal consultations in
      rural primary healthcare (PHC) facilities in Burkina Faso, Ghana and Tanzania; to
      (ii) assess pregnant women's awareness of these danger signs; and (iii) to
      identify factors affecting counselling practices and women's awareness. METHODS:
      Cross-sectional study in rural PHC facilities in Burkina Faso, Ghana and
      Tanzania. In each country, 12 facilities were randomly selected. WHO guidelines
      were used as standard for good counselling. We assessed providers' counselling
      practice on seven danger signs through direct observation study (35
      observations/facility). Exit interviews (63 interviews/facility) were used to
      assess women's awareness of the same seven danger signs. We used negative
      binomial regression to assess associations with health services' and socio
      demographic characteristics and to estimate per study site the average number of
      danger signs on which counselling was provided and the average number of danger
      signs mentioned by women. RESULTS: About one in three women was not informed of
      any danger sign. For most danger signs, fewer than half of the women were
      counselled. Vaginal bleeding and severe abdominal pain were the signs most
      counselled on (between 52% and 66%). At study facilities in Burkina Faso, 58% of
      the pregnant women were not able to mention a danger sign, in Ghana this was 22%
      and in Tanzania 30%. Fever, vaginal bleeding and severe abdominal pain were the
      danger signs most frequently mentioned. The type of health worker (depending on
      the training they received) was significantly associated with counselling
      practices. Depending on the study site, characteristics significantly associated
      with awareness of signs were women's age, gestational age, gravidity and
      educational level. CONCLUSION: Counselling practice is poor and not very
      efficient. A new approach of informing pregnant women on danger signs is needed.
      However, as effects of antenatal care education remain largely unknown, it is
      very well possible that improved counselling will not affect maternal and newborn
      mortality and morbidity.

PMID- 24118566
TI  - Proliferation determined by ki67 marker and pCR in locally advanced breast cancer
      patients treated with neo-adjuvant chemotherapy.

PMID- 24118567
TI  - Atopy as a risk factor for thyroid autoimmunity in children affected with atopic
      dermatitis.
AB  - BACKGROUND: As a result of several clinical reports addressing coincidence or
      coprevalence of atopy and autoimmune disease such as multiple sclerosis and type
      I diabetes mellitus, there has been considerable interest in defining the
      relationship between the expression of allergic and autoimmune disease in
      populations of patients. Although thyroid autoimmunity has been regularly
      associated with chronic urticaria in children, the cofrequency of thyroid
      autoimmunity and atopic dermatitis has not yet been investigated. The aim of the
      study was to describe our experience with children affected by atopic dermatitis
      and associated thyroid autoimmunity. METHODS: From January 2010 to December 2012,
      147 children affected by atopic dermatitis were consecutively referred to the
      Pediatric Clinic of the Pediatric Department at the Second University of Naples.
      Seventy healthy children of comparable ages, unaffected by atopic dermatitis,
      atopy or thyroid disease, served as a control group. RESULTS: On the basis of
      skin prick test results we selected 54 IgE-mediated (36.7%) and 93 non-IgE
      mediated AD (63.3%) children. Fourteen of 147 patients (9.52%) showed increased
      levels of antithyroid antibodies. CONCLUSIONS: Our results therefore suggest that
      atopy, especially food allergy, and autoimmunity are two potential outcomes of
      dysregulated immunity.

PMID- 24118568
TI  - Dermoscopy and near-infrared fluorescence imaging of cutaneous larva migrans.

PMID- 24118569
TI  - Effect of multistep processing technique on the formation of micro-defects and
      residual stresses in zirconia dental restorations.
AB  - PURPOSE: The clinical failures of zirconia dental restorations are often caused
      by extrinsic artifacts introduced by processing. The aim of this study was to
      investigate the micro-defects and residual stresses generated during the
      multistep process of zirconia dental restorations. MATERIALS AND METHODS: Thermal
      spray granulated 3Y-TZP powders were dry pressed by two tools exhibiting
      distinctly different Young's moduli, cold isostatic pressed (CIP-ed), and
      pressure-less fully sintered. The green bodies pressed by a stiff tool were
      treated with different procedures: direct milling (green milling) followed by
      fully sintering; half-sintering and milling (raw milling) with or without fully
      sintering; and fully sintering followed by grinding. The fully sintered 3Y-TZP
      crowns were clinically adjusted using both a diamond bur and SiC bur,
      respectively. Phase composition and microstructure of the pressed, milled, and
      ground surfaces were studied by XRD and SEM. RESULTS: Tetragonal phase was the
      main phase of all detected 3Y-TZP specimens. Excessive residual stresses
      introduced by raw milling and grinding were confirmed by a strained T (111) peak,
      monoclinic phase, and obviously changed I(002)t /I(200)t ratio. The residual
      stresses would form a compressive stress layer, while it was too shallow to
      inhibit crack propagation even for ground specimens. Large voids with high
      coordination numbers were the common packing micro-defects. Once formed, they
      were barely healed by CIP-ing and sintering. A stiff pressing tool was confirmed
      to be useful for reducing the surface packing voids. Milling removed the surface
      voids, but was no help for the interior ones. Raw milling introduced more serious
      chippings, most originating from the existing packing voids, than green milling
      due to its brittle failure and was less recommended for production. Grinding
      dense 3Y-TZP caused surface grain refinement and much more severe micro-defects,
      especially when clinical adjustment was applied by diamond bur compared to SiC
      bur. CONCLUSIONS: Micro-defects and residual stresses are introduced and
      accumulated through the entire production chain and determine the final
      microstructure of zirconia dental restorations. Several procedural improvements
      are offered and expected to reduce processing micro-defects.

PMID- 24118570
TI  - Transcriptional coupling of DNA repair in sporulating Bacillus subtilis cells.
AB  - In conditions of halted or limited genome replication, like those experienced in
      sporulating cells of Bacillus subtilis, a more immediate detriment caused by DNA
      damage is altering the transcriptional programme that drives this developmental
      process. Here, we report that mfd, which encodes a conserved bacterial protein
      that mediates transcription-coupled DNA repair (TCR), is expressed together with
      uvrA in both compartments of B. subtilis sporangia. The function of Mfd was found
      to be important for processing the genetic damage during B. subtilis sporulation.
      Disruption of mfd sensitized developing spores to mitomycin-C (M-C) treatment and
      UV-C irradiation. Interestingly, in non-growing sporulating cells, Mfd played an
      anti-mutagenic role as its absence promoted UV-induced mutagenesis through a
      pathway involving YqjH/YqjW-mediated translesion synthesis (TLS). Two
      observations supported the participation of Mfd-dependent TCR in spore
      morphogenesis: (i) disruption of mfd notoriously affected the efficiency of B.
      subtilis sporulation and (ii) in comparison with the wild-type strain, a
      significant proportion of Mfd-deficient sporangia that survived UV-C treatment
      developed an asporogenous phenotype. We propose that the Mfd-dependent repair
      pathway operates during B. subtilis sporulation and that its function is required
      to eliminate genetic damage from transcriptionally active genes.

PMID- 24118571
TI  - Severe conjunctivitis due to multidrug-resistant Neisseria gonorrhoeae and
      adenovirus 53 coinfection in a traveler returning from Thailand.
AB  - A male traveler returning from Thailand with severe bilateral conjunctivitis was
      tested for causative pathogens by culture and polymerase chain reaction in late
      2010. The culturally grown Neisseria gonorrhoeae strain was resistant against
      penicillin, ciprofloxacin, and tetracycline. The patient was also found to have
      an eye infection with the unusual and likely recombinant adenovirus type 53.
      Besides multidrug-resistant gonococcal strains the unusual adenovirus strain is
      found circulating in Asia and both pathogens may be a risk for travelers. 

PMID- 24118573
TI  - Administration of oral and vaginal prebiotic lactoferrin for a woman with a
      refractory vaginitis recurring preterm delivery: appearance of lactobacillus in
      vaginal flora followed by term delivery.
AB  - Lactoferrin (LF) is one of the prebiotics present in the human body. A 38-year
      old multiparous woman with poor obstetrical histories, three consecutive preterm
      premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was
      referred to our hospital. She was diagnosed as having refractory vaginitis.
      Although estriol vaginal tablets were used for 4 months, the vaginitis was not
      cured. We administrated vaginal tablets and oral agents of prebiotic LF,
      resulting in a Lactobacillus predominant vaginal flora. When she was pregnant,
      she continued to use the LF, and the Lactobacillus in the vaginal flora was
      continuously observed during pregnancy. An elective cesarean section was
      performed at the 38th week of pregnancy. When the administration of LF was
      discontinued after the delivery, Lactobacillus in the vaginal flora was
      disappeared. 

PMID- 24118572
TI  - MAG2 and three MAG2-INTERACTING PROTEINs form an ER-localized complex to
      facilitate storage protein transport in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, MAIGO 2 (MAG2) is involved in protein transport between
      the endoplasmic reticulum (ER) and the Golgi apparatus via its association with
      the ER-localized t-SNARE components SYP81/AtUfe1 and SEC20. To characterize the
      molecular machinery of MAG2-mediated protein transport, we explored MAG2
      interacting proteins using transgenic A. thaliana plants expressing TAP-tagged
      MAG2. We identified three proteins, which were designated as MAG2-INTERACTING
      PROTEIN 1-3 [MIP1 (At2g32900), MIP2 (At5g24350) and MIP3 (At2g42700)]. Both MIP1
      and MAG2 localized to the ER membrane. All of the mag2, mip1, mip2 and mip3
      mutants exhibited a defect in storage protein maturation, and developed abnormal
      storage protein body (MAG body) structures in the ER of seed cells. These
      observations suggest that MIPs are closely associated with MAG2 and function in
      protein transport between the ER and Golgi apparatus. MIP1 and MIP2 contain a
      Zeste-White 10 (ZW10) domain and a Sec39 domain, respectively, but have low
      sequence identities (21% and 23%) with respective human orthologs. These results
      suggest that the plant MAG2-MIP1-MIP2 complex is a counterpart of the triple
      subunit tethering complexes in yeast (Tip20p-Dsl1p-Sec39p) and humans (RINT1-ZW10
      NAG). Surprisingly, the plant complex also contained a fourth member (MIP3) with
      a Sec1 domain. There have been no previous reports showing that a Sec1-containing
      protein is a subunit of ER-localized tethering complexes. Our results suggest
      that MAG2 and the three MIP proteins form a unique complex on the ER that is
      responsible for efficient transport of seed storage proteins.

PMID- 24118574
TI  - Convergence of gut microbiomes in myrmecophagous mammals.
AB  - Mammals have diversified into many dietary niches. Specialized myrmecophagous
      (ant- and termite-eating) placental mammals represent a textbook example of
      evolutionary convergence driven by extreme diet specialization. Armadillos,
      anteaters, aardvarks, pangolins and aardwolves thus provide a model system for
      understanding the potential role of gut microbiota in the convergent adaptation
      to myrmecophagy. Here, we expand upon previous mammalian gut microbiome studies
      by using high-throughput barcoded Illumina sequencing of the 16S rRNA gene to
      characterize the composition of gut microbiota in 15 species representing all
      placental myrmecophagous lineages and their close relatives from zoo- and field
      collected samples. We confirm that both diet and phylogeny drive the evolution of
      mammalian gut microbiota, with cases of convergence in global composition, but
      also examples of phylogenetic inertia. Our results reveal specialized placental
      myrmecophages as a spectacular case of large-scale convergence in gut microbiome
      composition. Indeed, neighbour-net networks and beta-diversity plots based on
      UniFrac distances show significant clustering of myrmecophagous species
      (anteaters, aardvarks and aardwolves), even though they belong to
      phylogenetically distant lineages representing different orders. The aardwolf,
      which diverged from carnivorous hyenas only in the last 10 million years,
      experienced a convergent shift in the composition of its gut microbiome to become
      more similar to other myrmecophages. These results confirm diet adaptation to be
      a major driving factor of convergence in gut microbiome composition over
      evolutionary timescales. This study sets the scene for future metagenomic studies
      aiming at evaluating potential convergence in functional gene content in the
      microbiomes of specialized mammalian myrmecophages.

PMID- 24118575
TI  - Why tuberculosis service providers do not follow treatment guideline in Ethiopia:
      a qualitative study.
AB  - AIM: Little is known about the reasons why tuberculosis (TB) service providers do
      not follow TB treatment guidelines. A better understanding of their real-world
      experiences associated with non-compliance with guideline may highlight
      opportunities for enhanced TB care. Whether the problem is actual or perceived
      may also affect the type of intervention needed to overcome the barrier. This
      study aimed to explore TB service providers' reasons for not complying with TB
      treatment guidelines. METHOD: A descriptive qualitative design was used. Focus
      group discussions were held with 39 service providers involved in TB care. The
      study was carried out in the Tigray region of Ethiopia, in four of the six zonal
      hospitals. Data were analysed using content analysis. RESULTS: The main reasons
      for non-compliance with TB treatment guidelines were: (1) insufficient diagnostic
      modalities, limiting the capacity to correctly diagnose TB and provide the right
      regimen; (2) ambiguity in guideline recommendations especially for specific
      subgroups of patients, making it difficult to prioritize them to the right
      regimen; and (3) poor documentation concerning referred patients, with no
      appropriate examination and difficulty obtaining information from previously
      treated patients. CONCLUSION: Non-compliance may reflect valid questions about
      the applicability of guideline recommendations in the local context of health
      care. Special consideration should be given to previously treated patients, as an
      important factor influencing guideline compliance. Guideline compliance may also
      be improved by a better strategy to retest those patients whose initial tests are
      negative in health care contexts where TB is frequently missed.

PMID- 24118576
TI  - Editorial Comment to Different methods of hilar clamping during partial
      nephrectomy: impact on renal function.

PMID- 24118577
TI  - The role of disease severity in influencing body mass index in people with
      haemophilia: a single-institutional cross-sectional study.
AB  - The aim of this study was to evaluate the effect of haemophilia disease severity
      and potential intermediaries on body mass index (BMI) in patients with
      haemophilia. A secondary analysis of a cross-sectional study of 88 adults with
      haemophilia was undertaken. On bivariate analysis, persons with severe
      haemophilia had 9.8% lower BMI (95% CI -17.1, -3.0) than persons with non-severe
      haemophilia. The effect of haemophilia severity on BMI varied significantly by
      human immunodeficiency virus (HIV) status. Among HIV-positive subjects,
      haemophilia severity was not associated with BMI (+5.0%, 95% CI -22.4, 41.9).
      Among HIV-negative subjects, severe haemophilia was associated with 15.1% lower
      BMI (95% CI, -23.6, -5.7). Older (>41 years) HIV-negative subjects with severe
      haemophilia had a BMI that was 24.8% lower (95% CI -39.1, -7.0) than those with
      non-severe haemophilia. No statistically significant association was detected
      between BMI and severe vs. non-severe haemophilia for younger HIV-negative
      subjects. Although joint disease, as measured by the World Federation of
      Hemophilia (WFH) joint score, did not influence the association between
      haemophilia disease severity and BMI, adjustment for the atrophy component of the
      WFH score reduced the association between haemophilia severity and BMI by 39.1
      69.9%. This suggested that muscle atrophy mediated at least part of the
      relationship between haemophilia severity and BMI. Haemophilia disease severity
      is associated with BMI and appears to be mediated by muscle atrophy of
      surrounding joints. This association appears to be modified by HIV status and
      possibly age.

PMID- 24118578
TI  - Transmission of Staphylococcus aureus between mothers and infants in an African
      setting.
AB  - Staphylococcus aureus colonization is a risk factor for invasive disease. There
      is a need to understand S. aureus colonization in infancy as the burden of S.
      aureus infections in infants is high. We aimed to investigate the transmission of
      S. aureus between mothers and their newborns during the first year after delivery
      in an African setting. In a longitudinal cohort study, colonization of Gabonese
      mother-infant pairs was assessed at delivery and after 1, 9 and 12 months. Swabs
      were taken from mothers (nares, mammillae) and infants (nares and throat).
      Isolates were characterized and risk factors for colonization were assessed using
      a standardized questionnaire. We recruited 311 mothers and 318 infants including
      seven sets of twins. Maternal and infant colonization rates declined
      synchronously following a peak after 1 month at 40% (mothers) and 42% (infants).
      Maternal colonization was a risk factor for S. aureus carriage in infants. Based
      on spa typing, direct mother-to-infant transmission was evident in 5.6%. Of all
      methicillin-resistant isolates (n = 9), 44.4% were related to the USA300 clone;
      56.7% (n = 261) of all S. aureus carried Panton-Valentine leukocidin encoding
      genes. Direct mother-to-infant transmission was rare and cannot explain the
      increase of carriage in infants within the first month. A transmission from
      external sources is likely and challenges the S. aureus infection control in
      newborns and infants in an African setting. The detection of USA300-related MRSA
      fuels the concern about the spread of this clone in Central Africa.

PMID- 24118579
TI  - Donor-specific HLA antibodies: evaluating the risk for graft loss in renal
      transplant recipients with isotype switch from complement fixing IgG1/IgG3 to
      noncomplement fixing IgG2/IgG4 anti-HLA alloantibodies.
AB  - Human leukocyte antigen alloantibodies have a multitude of damaging effects on
      the allograft, both complement (C') activation and Fc-independent ones. To date,
      the clinical significance of non-C' fixing (NCF) HLA donor-specific antibodies
      (DSA) is still unclear. In this study, we investigated whether renal transplant
      recipients with NCF-DSA subclasses (IgG2/IgG4, IgA1/IgA2) are at higher risk of
      graft loss compared to patients with exclusively C' fixing (IgG1/IgG3). Blood
      samples from 274 patients were analyzed for HLA IgG and IgA subclasses using a
      modified single-antigen bead assay. We identified 50 (18.2%) patients with
      circulating NCF antibodies either DSA (n=17) or against third-party HLA (n=33).
      NCF-DSAs were preferentially of IgG2/IgG4 isotype (11/17) and were mainly
      directed against HLA class II (13/17). NCF DSA were present as a mixture with
      strong C' fixing IgG1/IgG3. Graft survival was similar between patients with
      exclusively C' fixing antibodies and those with a mixture panel (log rang test
      P=0.162), and also among patients with different immunoglobulin isotype and
      subclasses (long-rank test, P=0.732). We conclude that expansion of DSA to NCF
      subclasses postrenal transplantation does not seem to be associated with worse
      graft survival as compared to the presence of exclusive C' fixing subclasses.

PMID- 24118580
TI  - 3D cardiovascular navigation system: accuracy and reduction in radiation exposure
      in left ventricular lead implant.
AB  - INTRODUCTION: Cardiac resynchronization therapy implants entail significant
      radiation exposure for patients and physicians. A novel 3D electromagnetic
      cardiovascular navigation system (MediGuideTM) was designed to superimpose the
      real-time location of sensors embedded in delivery tools on prerecorded coronary
      sinus (CS) venograms while adjusting for patient movement and variations in heart
      rate under different C-arm angulations. We studied the accuracy and efficacy of
      MediGuideTM in reducing radiation exposure during LV lead implants. METHODS AND
      RESULTS: Fluoroscopy durations and radiation exposures were measured in 6 canines
      undergoing both conventional and MediGuideTM-guided LV lead implants. The in vivo
      accuracy of MediGuideTM was evaluated by obtaining CS venograms at 3 different C
      arm angulations at 3 different heart rates and measuring the separation between
      the projected sensor icon of a MediGuideTM sensor-enabled guidewire and the
      encompassing branch on prerecorded venograms. RESULTS: MediguideTM-guided
      implants resulted in significant reductions in fluoroscopy time (52 +/- 120
      [median 6] vs 129 +/- 118 [median 90] sec, P < 0.001) and radiation exposure
      (13.8 +/- 32.4 [median 1.7] vs 49.2 +/- 45.3 [median 27.2] MUGym(2) , P = 0.03)
      compared to conventional implants. LV lead delivery time was not significantly
      different between the 2 implant techniques (P = 0.27). The mean separation
      between the projected guidewire sensor icon and its encompassing branch was 0.48
      +/- 0.94 (median 0.00) mm. System accuracy was not affected by variations in
      heart rate or C-arm angulations. CONCLUSION: The novel 3D cardiovascular
      navigation system enabled accurate and reliable tracking of sensor-enabled tools
      at varying heart rates and C-arm angulations with minimal need for fluoroscopy
      guidance, significantly reducing fluoroscopy time and radiation exposure.

PMID- 24118581
TI  - Media use for seeking health/cancer-related information: findings from knowledge,
      attitudes and practices towards cancer prevention and care survey in Jordan.
AB  - Understanding of public health/cancer information-seeking behaviour could play
      key role in promoting health behaviour and reducing cancer burden. In the current
      study, data from 'Knowledge, Attitudes and Practices toward Cancer Prevention and
      Care Survey in Jordan' were used. A total of 3196 participants (18 years and
      older) were included in the study. The results indicated that 82% (n = 2609) of
      the participants had never looked for health/cancer information from any sources.
      The majority of those surveyed (97%) reported watching TV habitually, whereby 948
      participants (26%) indicated that they watched health information on the
      local/satellite TV channels, whereas 1603 (45%) reported doing so on non
      local/satellite TV channels. Internet was the most searched source for
      information (36%); however, it is one of least preferred sources. Health-care
      providers are the most preferred source for cancer-related information, followed
      by TV and someone with cancer. The majority of participants (82%; n = 489)
      indicated the absence of barriers in seeking information about cancer. The
      results suggest that although the Jordanian public use of different media and
      channels for seeking health/cancer-related information, health-care providers and
      TV might be effective tools for health education. In addition, joint efforts must
      be established to initiate awareness programmes at the local and regional levels.

PMID- 24118582
TI  - Telomere length loss due to smoking and metabolic traits.
AB  - OBJECTIVES: Human age-dependent telomere attrition and telomere shortening are
      associated with several age-associated diseases and poorer overall survival. The
      aim of this study was to determine longitudinal leucocyte telomere length
      dynamics and identify factors associated with temporal changes in telomere
      length. DESIGN AND METHODS: Leucocyte telomere length was measured by
      quantitative polymerase chain reaction in 8074 participants from the Prevention
      of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community
      based prospective cohort study initiated in 1997. Follow-up data were available
      at two time-points up to 2007. Leucocyte telomere length was measured, on between
      one and three separate occasions, in a total of 16 783 DNA samples. Multilevel
      growth models were created to identify the factors that influence leucocyte
      telomere dynamics. RESULTS: We observed an average attrition rate of 0.47 +/-
      0.16 relative telomere length units (RTLUs) per year in the study population aged
      48 (range 39-60) years at baseline. Annual telomere attrition rate increased with
      age (P < 0.001) and was faster on average in men than in women (P for interaction
      0.043). The major independent factors determining telomere attrition rate were
      active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and
      multiple traits of the metabolic syndrome (waist-hip ratio, P = 0.007; blood
      glucose level, P = 0.045, and HDL cholesterol level, P < 0.001). CONCLUSIONS:
      Smoking and variables linked to the metabolic syndrome are modifiable lifestyle
      factors that accelerate telomere attrition in humans. The higher rate of cellular
      ageing may mediate the link between smoking and the metabolic syndrome to an
      increased risk of several age-associated diseases.

PMID- 24118583
TI  - Balloon cinch deformity during angioplasty procedures: an indication for
      impending rupture.
AB  - Percutaneous transluminal balloon angioplasty (PTA) is a commonly performed
      procedure for hemodialysis vascular access dysfunction including thrombosis.
      While PTA is generally safe, balloon rupture during the procedure is a potential
      complication. Because such a rupture can cause damage to the blood vessel,
      indication of an imminent balloon rupture might help avoid such a complication.
      This analysis reports on six PTA procedures that were complicated by balloon
      rupture. All cases demonstrated terminal (caudal/cranial) cinch deformation.
      There was a loss of sharp terminal tapering and its replacement with banana
      silhouette before the balloon rupture. Importantly, the contour deformation and
      balloon rupture occurred at a pressure that was lower than the rated burst
      pressure. The cinch deformity can be used as an indication for impending balloon
      rupture. We suggest deflation of balloons that demonstrate shape deformations to
      avoid vascular injury. 

PMID- 24118584
TI  - The effect of task-irrelevant visual backgrounds on human transcranial magnetic
      stimulation-evoked electroencephalography responses and cortical alpha activity.
AB  - Brain responses evoked by transcranial magnetic stimulation (TMS) in task-free
      experimental contexts are known to depend on psychophysiological states such as
      sleep, vegetative state and caffeine-induced arousal. Much less is known about
      how TMS-evoked responses depend on task-irrelevant steady perceptual input. Here,
      we examined ongoing alpha activity and the mean amplitude of EEG potentials in
      response to occipitally applied TMS as a function of task-irrelevant visual
      backgrounds. Responses to TMS were robustly modulated by photographs of natural
      scenes and man-made environments. These effects began as early as during the N100
      and continued for several hundred milliseconds after the stimulation. There was
      also a more general effect of background along with other stimuli, such as blank
      backgrounds, sinusoidal gratings and moving dot-patterns. This effect was
      observable from ongoing alpha activity as well. Based on these results we
      conclude that different types of steady perceptual input modulate visual cortex
      reactivity and/or connectivity and it is possible to measure these modulations by
      combining TMS with electroencephalography. 

PMID- 24118585
TI  - Spontaneous bacterial peritonitis as a presenting feature of nephrotic syndrome.

PMID- 24118586
TI  - Allotransplanting donor kidneys after resection of a small renal cancer or
      contralateral healthy kidneys from cadaveric donors with unilateral renal cancer:
      a systematic review.
AB  - This systematic review summarizes evidence on allotransplantation of donor
      kidneys after resection of a small renal cancer or contralateral healthy kidneys
      from cadaveric donors with unilateral renal cancer. Eligible studies were
      identified by screening four bibliographic databases, contacting key authors, and
      analyzing the bibliographies of included studies. Two reviewers independently
      assessed the reports for inclusion and extracted data, which were summarized as a
      narrative review. In the 20 case report or case series studies included in the
      analysis, there were 97 documented cases of donor kidney transplantation after
      resection of small renal cancer without pathologically confirmed recurrence,
      whereas 22 cases used contralateral healthy kidneys from cadaveric donors with
      unilateral renal cancer with one case of cancer recurrence. These results suggest
      that the use of donor kidneys after resection of small renal cancer is associated
      with a relatively low cancer recurrence rate. 

PMID- 24118587
TI  - Group psychotherapy in women with a history of sexual abuse: what did they find
      helpful?
AB  - AIMS AND OBJECTIVES: To define the effects of group psychotherapy in women with a
      history of sexual abuse, to find possible predictors for dropout and treatment
      outcome rates and to find which therapeutic factors of group psychotherapy are
      perceived by group members to be most helpful. BACKGROUND: Sexual abuse of women
      is a global concern and causes many psychiatric and psychological sequelae. Group
      psychotherapy is one of the preferred treatment modalities. DESIGN: Prospective
      cohort study. METHODS: Forty-seven women with a history of childhood and/or
      adulthood sexual abuse were recruited for weekly 12-session group psychotherapy.
      Subjects were given the Hamilton Depression Rating Scale, the Hamilton Anxiety
      Rating Scale, the Clinician Administered Post-traumatic Stress Disorder Scale,
      the Dissociative Experiences Scale, the Childhood Trauma Questionnaire and the
      Group Therapeutic Factors Questionnaire. Re-evaluations were made after the 6th
      and 12th session and also at a six-month follow-up session. RESULTS: Group
      psychotherapy significantly reduced participants' levels of depression
      (screening/12th session mean scores, 22.45/11.10), anxiety (15.45/4.32) and
      symptoms of post-traumatic stress disorder (42.27/9.32), and this decline became
      statistically significant at the 6th session and tended to persist at the six
      month follow-up. Higher levels of dissociative symptoms at baseline were
      associated with less response to treatment, but higher levels of attendance at
      group sessions. Group members rated existential factors (41.40 +/- 12.39),
      cohesiveness (37.42 +/- 8.32) and universalism (37.56 +/- 7.11) as the most
      helpful therapeutic factors. CONCLUSION: Group psychotherapy was significantly
      effective in reducing levels of depression, anxiety and posttraumatic stress
      disorder symptoms in this sample of women. Dissociation had a significant effect
      on both treatment outcome and treatment adherence. For this sample of women,
      group psychotherapy was most helpful for reducing feelings of stigma, isolation
      and shame. RELEVANCE TO CLINICAL PRACTICE: Group psychotherapy can be used as a
      preferred treatment method for women from different cultural backgrounds with a
      history of sexual abuse.

PMID- 24118588
TI  - Cuticular hydrocarbon divergence in the jewel wasp Nasonia: evolutionary shifts
      in chemical communication channels?
AB  - The evolution and maintenance of intraspecific communication channels constitute
      a key feature of chemical signalling and sexual communication. However, how
      divergent chemical communication channels evolve while maintaining their
      integrity for both sender and receiver is poorly understood. In this study, we
      compare male and female cuticular hydrocarbon (CHC) profiles in the jewel wasp
      genus Nasonia, analyse their chemical divergence and investigate their role as
      species-specific sexual signalling cues. Males and females of all four Nasonia
      species showed unique, nonoverlapping CHC profiles unambiguously separating them.
      Surprisingly, male and female phylogenies based on the chemical distances between
      their CHC profiles differed dramatically, where only male CHC divergence
      parallels the molecular phylogeny of Nasonia. In particular, N. giraulti female
      CHC profiles were the most divergent from all other species and very different
      from its most closely related sibling species N. oneida. Furthermore, although
      our behavioural assays indicate that female CHC profiles can generally be
      perceived as sexual cues attracting males in Nasonia, this function has
      apparently been lost in the highly divergent female N. giraulti CHC profiles.
      Curiously, N. giraulti males are still attracted to heterospecific, but not to
      conspecific female CHC profiles. We suggest that this striking discrepancy has
      been caused by an extensive evolutionary shift in female N. giraulti CHC
      profiles, which are no longer used as conspecific recognition cues. Our study
      constitutes the first report of an apparent abandonment of a sexual recognition
      cue that the receiver did not adapt to. 

PMID- 24118590
TI  - Time in bed, sleep quality and associations with cardiometabolic markers in
      children: the Prevention and Incidence of Asthma and Mite Allergy birth cohort
      study.
AB  - We investigated associations of time in bed and multiple sleep quality
      characteristics with cardiometabolic markers in children. Data from the
      prevention and incidence of asthma and mite allergy study, a population-based
      prospective birth-cohort study started in 1996-1997 in the Netherlands, were
      analysed. In total 1481 children aged 11-12 years completed a questionnaire
      (including questions on sleep) and underwent a medical examination. We measured
      body mass index, waist circumference, total- and high-density lipoprotein
      cholesterol, blood pressure and glycated haemoglobin. Results showed that in
      girls, some sleep characteristics were related to anthropometrics (body mass
      index, waist circumference) and cholesterol. Girls who had a long time in bed (11
      12.5 h) had 0.16 lower body mass index z-score (95% confidence interval -0.31; 
      0.01) and 0.99 cm smaller waist circumference (95% confidence interval -2.01; 
      0.13) compared with girls who spent 10-10.5 h in bed. Girls who went to bed late
      and rose early had 0.16 mm higher total cholesterol (95% confidence interval
      0.01; 0.31) and 0.08 mm higher high-density lipoprotein cholesterol (95%
      confidence interval 0.01; 0.14) than 'early to bed/early rise' girls. Girls with
      night-time awakenings had 0.14 mm higher total cholesterol (95% confidence
      interval 0.03; 0.25) than girls without night-time awakenings. Girls who felt
      sleepy/tired >=1 day per week had 0.10 mm lower high-density lipoprotein
      cholesterol (95% confidence interval -0.16; -0.04) and 0.17 mm higher total
      cholesterol/high-density lipoprotein cholesterol ratio (95% confidence interval
      0.02; 0.32) than girls who did not feel sleepy. No associations were found for
      boys. Sleep characteristics were not related to blood pressure and glycated
      haemoglobin, and effect sizes of the associations in girls were small. Therefore,
      we consider it premature to propose that improved sleep could reduce
      cardiovascular risk during childhood.

PMID- 24118589
TI  - AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats
      following esophageal acid exposure.
AB  - BACKGROUND: We recently reported an increase in N-methyl-d-aspartate (NMDA)
      receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the
      rostral cingulate cortical (rCC) neurons following esophageal acid exposure in
      rats. As alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      receptors mediate the fast excitatory transmission and play a critical role in
      synaptic plasticity, in this study, we investigated the effect of esophageal acid
      exposure in rats on the expression of AMPA receptor subunits and the involvement
      of these molecular alterations in acid-induced sensitization of neurons in the
      anterior cingulate (ACC) and midcingulate (MCC) cortices. METHODS: In molecular
      study, we examined GluA1 and GluA2 expression and phosphorylation in membrane
      preparations and in the isolated postsynaptic densities (PSDs) from rats
      receiving acute esophageal exposure of either saline (control group) or 0.1 N HCl
      (experimental group). In electrophysiological study, the effect of selective AMPA
      receptor (Ca(2+) permeable) antagonist IEM-1460 and CaMKII inhibitor KN-93 was
      tested on responses of cortical neurons during acid infusion to address the
      underlying molecular mechanism of acid-induced sensitization. KEY RESULTS: The
      acid exposure significantly increased expression of GluA1, pGluA1Ser(831) , and
      phosphorylated CaMKIIThr(286) , in the cortical membrane preparations. In
      isolated PSDs, a significant increase in pGluA1Ser(831) was observed in acid
      treated rats compared with controls. Microinjection of IEM-1460 or KN-93 near the
      recording site significantly attenuated acid-induced sensitization of cortical
      neurons. CONCLUSIONS & INFERENCES: The underlying mechanism of acid-induced
      cortical sensitization involves upregulation and CaMKII-mediated phosphorylation
      of GluA1. These molecular changes of AMPA receptors subunit GluA1 in the cortical
      neurons might play an important role in acid-induced esophageal hypersensitivity.

PMID- 24118591
TI  - Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta
      (PPARD) gene is associated with elite athletic status.
AB  - Peroxisome proliferator-activated receptor delta (PPARdelta; encoded by the PPARD
      gene) plays a role in energy metabolism and mitochondrial function. We have
      investigated the distribution of PPARD rs2267668, rs2016520 and rs1053049
      polymorphisms, individually and in haplotype, in a cohort of 660 elite athletes
      which was subdivided into four different groups based on the different metabolic
      demands of their respective sports and 704 healthy controls. PPARD rs2016529 and
      rs1053049 were individually associated with overall elite athletic performance (P
      = 0.00002; and P = 0.0002) and also with athletes grouped as strength endurance
      (P = 0.00008; and P = 0.0003). Furthermore, PPARD A/C/C haplotype
      (rs2267668/rs2016520/rs1053049) was significantly underrepresented in all
      athletes and each subgroup of athletes when compared with controls (P <
      0.000001), suggesting that harboring this specific haplotype is unfavorable for
      becoming an elite athlete. These results help to identify which genetic profiles
      may contribute to elite athletic performance, specifically the role of variants
      within the PPARD gene, and may be useful in talent identification or optimizing
      the response to training.

PMID- 24118592
TI  - Accuracy and completeness of patient information in organic World-Wide Web search
      for Mohs surgery: a prospective cross-sectional multirater study using consensus
      criteria.
AB  - BACKGROUND: Many patients obtain medical information from the Internet.
      Inaccurate information affects patient care and perceptions. OBJECTIVE: To assess
      the accuracy and completeness of information regarding Mohs micrographic surgery
      (MMS) on the Internet. METHODS: Prospective cross-sectional Internet-based study
      reviewing 30 consecutive organic results from three U.S. urban areas on "Mohs
      surgery" using Google. Text was assessed using a consensus-derived rating scale
      that quantified necessary and additional or supplementary information about MMS,
      as well as wrong information. Websites were classified according to type of
      sponsor. RESULTS: Ninety-one percent of sites conveyed basic information about
      MMS. There was variation in the mean amount of additional information items
      (range 0-9) according to website type: 8.4, medical societies; 6.7, academic
      practices; 5.9, web-based medical information resources; 4.7, private practices;
      and 4.4, other (p < .001). Cumulatively, academic practices and professional
      societies (mean 7.42) provided more additional information than private practices
      and web-based sources (mean 5.11, p < .001). There were no differences based on
      geographic location. Wrong items included misspelling Mohs (10%), indicating that
      only plastic surgeons could reconstruct (7%), and noting MMS was never cost
      effective (7%). CONCLUSIONS: High-ranking websites provide basic information
      about MMS. Academic practice and professional society sites provide more
      comprehensive information, but private practice sites and web-based medical
      information sources also provide additional information.

PMID- 24118593
TI  - Treatment of earlobe keloids by surgical excision and cryosurgery.
AB  - BACKGROUND: The long-term results of keloid treatments remain poor. OBJECTIVE: To
      assess the long-term efficacy of a technique combining surgical excision and
      immediate cryosurgery in patients with ear keloids. METHODS: A retrospective
      study was performed between January 2001 and June 2011. All patients referred for
      treatment of an ear keloid and undergoing subsequent surgical excision followed
      by immediate freezing of the postoperative wound using cryosurgery were included.
      The primary end-point was the number of patients who achieved major flattening of
      the keloid (defined as a reduction of more than 80% of the keloid) at the time of
      the study after a minimum follow-up of 24 months after treatment. RESULTS: Sixty
      six patients with a total of 97 keloids were included. Median follow-up time
      after treatment was 43 months. 'Major' flattening was observed in 69 keloids
      (71%). Fifty-six of these lesions (81%) were treated with one session and 13
      (19%) required a second session after keloid recurrence. Fifteen lesions (15%)
      were considered 'treatment failure', including 11 keloids in eight patients who
      were lost to follow-up and four keloids which achieved less than 30% reduction of
      their surface. Thirteen other keloids were evaluated as displaying significant or
      moderate improvement. Treatment side-effects were partial amputation of the ear
      lobe in three patients with a very large keloid of the ear lobe and
      hypopigmentation in five patients. LIMITATION: Retrospective study. CONCLUSION:
      The combination of surgical excision and cryosurgery can be considered for the
      treatment of large ear keloids.

PMID- 24118594
TI  - Awareness, attitude, and expectations toward dental implants among removable
      prostheses wearers.
AB  - PURPOSE: To assess removable denture patient awareness, expectations, and source
      of information about dental implants (DIs). MATERIALS AND METHODS: Three hundred
      patients [150 removable partial denture (RPD) wearers and 150 complete denture
      wearers (CDWs)] attended the removable prosthodontic clinic at Faculty of
      Dentistry, Jordan University of Science and Technology. Patients were evaluated
      using a pilot-tested, 21-question questionnaire. RESULTS: Ninety-six percent of
      participants were aware of DIs, with no difference between CDWs and RPD wearers
      (p > 0.05). The participants' friends and relatives were the main source of
      information (63.4%), followed by dentists (32.4%). Improvement in function was
      the predominant reason (55.7%) for patients to consider DIs. Fear of unknown side
      effects was the major factor in preventing patients from choosing DIs (11.7%),
      followed by high cost (9.7%) and surgical risk (8.7%). Approximately 89% had no
      information or were poorly informed about DIs. Over two-thirds of patients did
      not know about the care (78.3%) of DIs, causes of DI failure (69.7%), or DI
      duration of service (80.7%). Only 24.7% knew that DIs would be anchored to the
      jawbone; however, 27.3% and 56.7% of CDWs and RPD wearers, respectively,
      preferred (p < 0.05) to have their teeth replaced with DIs. High costs were
      considered the major disadvantage of DIs in 45% of participants, followed by fear
      of surgery (27.3%), and long treatment times (24.7%). CONCLUSIONS: There was a
      high awareness about DIs among removable denture patients; however, this
      awareness was associated with a low level of accurate information.

PMID- 24118595
TI  - Dengue fever, tuberculosis, human immunodeficiency virus, and hepatitis C virus
      conversion in a group of long-term development aid workers.
AB  - BACKGROUND: Development and humanitarian aid workers are a diverse group of
      travelers who, because of the nature of their travel, may have specific travel
      related health risks. The main objective of this study was to quantify the risk
      of dengue fever virus (DFV), tuberculosis (TB), human immunodeficiency virus
      (HIV), and hepatitis C virus (HCV) infections in a group of long-term development
      aid volunteers. METHODS: Medical files of Volunteer Service Abroad (VSA)
      volunteers and their accompanying family/partner/spouse serving over 17 years
      (1995-2011) were reviewed. Demographics, destination, months spent in-country,
      and, where available, results of pre- and post-assignment testing for DFV, TB,
      HCV and HIV infections were extracted. RESULTS: Results from 652 assignments were
      audited. Conversion rates were calculated when both pre- and post-assignment
      results were available. Evidence of dengue fever seroconversion was found in 6.3%
      of 205 volunteers [at a rate of 3.4 per 1,000 person months (pm) on assignment],
      with assignments in Southeast Asia having the highest risk. Evidence of TB during
      assignment was found in 2.9% of 336 volunteers converting at a rate of 1.4 per
      1,000 pm. There were no HIV or HCV infections detected. On post-assignment
      questioning, 6.7% of volunteers reported unprotected sex with someone other than
      their regular partner and 9.8% reported a potential exposure to blood and/or
      blood products. CONCLUSIONS: Infection with DFV and TB occurred in this group at
      rates similar to that seen in other groups of long-term travelers, and screening
      would appear to be warranted. While none contracted HIV or HCV infection,
      reported behavior did put them at risk of blood- and body fluid-borne diseases.
      It is important that pre-assignment travel health preparation in this group
      focuses on strategies to minimize these risks.

PMID- 24118596
TI  - Acquired factor V deficiency in a patient without evidence of a classical
      inhibitor.

PMID- 24118597
TI  - The effects of hoechst 33342 staining and the male sample donor on the sorting
      efficiency of canine spermatozoa.
AB  - The aim of this study was to evaluate the influence of Hoechst 33342 (H-42)
      concentration and of the male donor on the efficiency of sex-sorting procedure in
      canine spermatozoa. Semen samples from six dogs (three ejaculates/dog) were
      diluted to 100 * 10(6) sperm/ml, split into four aliquots, stained with
      increasing H-42 concentrations (5, 7.5, 10 and 12.5 MUl, respectively) and sorted
      by flow cytometry. The rates of non-viable (FDA+), oriented (OS) and selected
      spermatozoa (SS), as well as the average sorting rates (SR, sorted
      spermatozoa/s), were used to determine the sorting efficiency. The effects of the
      sorting procedure on the quality of sorted spermatozoa were evaluated in terms of
      total motility (TM), percentage of viable spermatozoa (spermatozoa with membrane
      and acrosomal integrity) and percentage of spermatozoa with reacted/damaged
      acrosomes. X- and Y-chromosome-bearing sperm populations were identified in all
      of the samples stained with 7.5, 10 and 12.5 MUl of H-42, while these two
      populations were only identified in 77.5% of samples stained with 5 MUl. The
      values of OS, SS and SR were influenced by the male donor (p < 0.01) but not by
      the H-42 concentration used. The quality of sorted sperm samples immediately
      after sorting was similar to that of fresh samples, while centrifugation resulted
      in significant reduction (p < 0.05) in TM and in the percentage of viable
      spermatozoa and a significant increase (p < 0.01) in the percentage of
      spermatozoa with damage/reacted acrosomes. In conclusion, the sex-sorting of
      canine spermatozoa by flow cytometry can be performed successfully using H-42
      concentrations between 7.5 and 12.5 MUl. The efficiency of the sorting procedure
      varies based on the dog from which the sperm sample derives. 

PMID- 24118598
TI  - Dramatic improvement in decompensated right heart failure due to severe tricuspid
      regurgitation following ligation of arteriovenous fistula in a renal transplant
      recipient.
AB  - Arteriovenous (AV) fistulas with high blood flow rate are necessary for adequate
      hemodialysis, but they can also cause significant hemodynamic changes, including
      raised cardiac output, left ventricular hypertrophy and occasionally overt
      cardiac failure (Basile et al., Nephrol Dial Transplant, 23, 2008, 282; Unger et
      al., Am J Transplant, 4, 2004, 2038). We now report a case of rapid and dramatic
      improvement in symptomatic right heart failure due to severe tricuspid
      regurgitation following ligation of an arteriovenous fistula. Cardiac magnetic
      resonance imaging (MRI) performed before and after the ligation of fistula showed
      striking improvement in both the tricuspid regurgitation and right ventricular
      dimensions, with minimal impact on left ventricular mass, size, and function. 

PMID- 24118599
TI  - Monkey gaze behaviour during action observation and its relationship to mirror
      neuron activity.
AB  - Mirror neurons (MNs) of the monkey ventral premotor cortex (area F5) are a class
      of cells that match the visual descriptions of others' actions with correspondent
      motor representations in the observer's brain. Several human studies suggest that
      one's own motor representations activated during action observation play a role
      in directing proactive eye movements to the site of the upcoming hand-target
      interaction. However, there are no data on the possible relationship between gaze
      behaviour and MN activity. Here we addressed this issue by simultaneously
      recording eye position and F5 MN activity in two macaques during free observation
      of a grasping action. More than half of the recorded neurons discharged stronger
      when the monkey looked at the action than when it did not look at it, but their
      firing rate was better predicted by 'when' rather than by 'how long' the monkey
      gazed at the location of the upcoming hand-target interaction. Interestingly, the
      onset of MN response was linked to the onset of the experimenter's movement, thus
      making motor representations potentially exploitable to drive eye movements.
      Furthermore, MNs discharged stronger and earlier when the gaze was 'proactive'
      compared with 'reactive', indicating that gaze behaviour influences MN activity.
      We propose that feedforward, automatic representations of other's actions could
      lead eye movements that, in turn, would provide the motor system with feedback
      information that enhances the neural representations of the ongoing action. 

PMID- 24118600
TI  - Factors associated with switching and combination use of antidepressants in young
      Swedish adults.
AB  - AIMS: Little is known on factors associated with switching and combination use of
      antidepressants. Our aim was to describe such use and to analyse the association
      with socioeconomic factors and level of care in Swedish adults aged 20-34 years.
      METHODS: Individuals, aged 20-34 years, who purchased an antidepressant in
      January-June 2006, and who had not purchased any antidepressant in the preceding
      6 months (n = 24,897) were followed from 6 up to 12 months. Among those who
      purchased >= 2 antidepressant substances, switchers were defined as those who did
      not fulfil the requirements for combination use. Data on purchased
      antidepressants and socioeconomic characteristics were obtained from the Swedish
      Prescribed Drug Register and Statistics Sweden. The association between (i) >= 2
      antidepressants or (ii) switching, respectively, and socioeconomic factors as
      well as level of care was analysed with multiple logistic regression. RESULTS: A
      total of 4254 individuals (17%) purchased >= 2 antidepressant substances, and the
      remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR)
      for purchase of >= 2 antidepressants (vs. purchase of one antidepressant only)
      was higher among those who started on mirtazapine compared with selective
      serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and
      lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of
      follow-up: 0.73 (0.62-0.85). Among those with >= 2 antidepressants, 71.6% were
      classified as switchers. The adjusted OR for switching (vs. combination use) were
      higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among
      individuals with short university education: 0.58 (0.43-0.78), those starting on
      mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric
      care: 0.75 (0.63-0.88). CONCLUSIONS: One of six new users purchased at least two
      antidepressants, the majority were classified as switchers. Purchase patterns
      were associated with socioeconomic characteristics, in particular level of
      education, type of first purchased antidepressant, and level of care initiating
      treatment.

PMID- 24118601
TI  - European Society of Clinical Microbiology and Infectious Diseases: update of the
      treatment guidance document for Clostridium difficile infection.
AB  - In 2009 the first European Society of Clinical Microbiology and Infection
      (ESCMID) treatment guidance document for Clostridium difficile infection (CDI)
      was published. The guideline has been applied widely in clinical practice. In
      this document an update and review on the comparative effectiveness of the
      currently available treatment modalities of CDI is given, thereby providing
      evidence-based recommendations on this issue. A computerized literature search
      was carried out to investigate randomized and non-randomized trials investigating
      the effect of an intervention on the clinical outcome of CDI. The Grades of
      Recommendation Assessment, Development and Evaluation (GRADE) system was used to
      grade the strength of our recommendations and the quality of the evidence. The
      ESCMID and an international team of experts from 11 European countries supported
      the process. To improve clinical guidance in the treatment of CDI,
      recommendations are specified for various patient groups, e.g. initial non-severe
      disease, severe CDI, first recurrence or risk for recurrent disease, multiple
      recurrences and treatment of CDI when oral administration is not possible.
      Treatment options that are reviewed include: antibiotics, toxin-binding resins
      and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal
      transplantation. Except for very mild CDI that is clearly induced by antibiotic
      usage antibiotic treatment is advised. The main antibiotics that are recommended
      are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly
      recommended for multiple recurrent CDI. In case of perforation of the colon
      and/or systemic inflammation and deteriorating clinical condition despite
      antibiotic therapy, total abdominal colectomy or diverting loop ileostomy
      combined with colonic lavage is recommended. 

PMID- 24118602
TI  - Families' needs of critical care Muslim patients in Saudi Arabia: a quantitative
      study.
AB  - AIM: To identify the needs of families of adult intensive care unit (ICU)
      patients in Saudi Arabia as perceived by family members and health care
      providers. BACKGROUND: Family members of critically ill patients are likely to
      have specific needs that should be addressed by the critical care team and which,
      if unmet, may produce stress for patients' families and health care providers.
      The literature has yet to identify the needs of Muslim families in relation to
      religious beliefs and cultural values in critical care settings in Saudi Arabia.
      DESIGN: A cross-sectional survey design. METHOD: A total of 176 family members
      and 497 intensive health care providers were recruited from eight adult mixed
      medical-surgical ICUs between November 2011 and February 2012 utilizing a four
      point Likert type scale self-administered questionnaire. RESULTS: The findings
      revealed that family members and health care providers ranked assurance,
      information and cultural and spiritual needs as the most important, and support
      and proximity as least important. There were significant differences in the mean
      values found between family members and health care providers. A significant
      finding not identified in other studies was 'The need to have the health care
      providers handle the body of the dead Muslim with extreme caution and respect'
      which, under the dimension of cultural and spiritual needs, was perceived by
      family members to be the most important and by the health care providers as the
      fifth most important need. CONCLUSION: The recognition of family needs in the
      critical care unit informed the development of interventions to meet family needs
      and improve the care quality.

PMID- 24118603
TI  - The ever-diminishing role of axillary lymph node dissection in breast cancer.

PMID- 24118604
TI  - Ex vivo bupivacaine treatment results in increased adipogenesis of skeletal
      muscle cells in the rat.
AB  - Intramuscular adipose tissue (IMAT) is observed in some skeletal muscle
      pathologies. IMAT is implicated not only in the disorders of muscle contraction,
      but also of metabolism and insulin sensitivity due to its nature as a secretary
      organ. Several studies indicate the presence of cells with adipogenic potential
      in skeletal muscle. However, the mechanism of fate specification that triggers
      these cells to enter an adipogenic program in vivo remains to be solved. In the
      present study, we examined whether activation of the adipogenic program of muscle
      resident cells precedes their proliferation upon muscle injury. For this purpose,
      muscle injury was induced by injecting bupivacaine (BPVC) to excised skeletal
      muscle ex vivo. Cells isolated from ex vivo BPVC-treated muscle exhibited higher
      adipogenic potential than those from saline-treated muscle. Pre-plating exposure
      of skeletal muscle cells to basic fibroblast growth factor (bFGF) mimicked the
      effect of ex vivo BPVC-treatment, suggesting that bFGF released from
      extracellular matrix in response to muscle injury activates their adipogenic
      program. Interestingly, the number of myotubes were significantly reduced in the
      culture from BPVC-treated muscle, suggesting that adipocytes negatively regulate
      myogenesis. 

PMID- 24118605
TI  - Cowden syndrome complicated by a gastrointestinal stromal tumor.
AB  - To our knowledge, this is the first report of Cowden syndrome complicated by a
      gastrointestinal stromal tumor (GIST) of the small bowel. A 42-year-old female
      patient was found to have an abdominal mass that was diagnosed as the cause of
      anemia and was surgically extracted. The surgical specimen was found to be a
      GIST. During the same period, the patient underwent an endoscopic examination of
      the entire gastrointestinal tract. She was also diagnosed as having Cowden
      syndrome based on gastrointestinal polyps and skin, thyroid and breast lesions.
      Cowden syndrome is associated with germline mutations in the tumorsuppressor gene
      PTEN. PTEN expression may be essential to tumor growth and is a predictive
      biomarker of the prognosis of both diseases. The present report of such a case is
      expected to further the analysis of Cowden syndrome. 

PMID- 24118606
TI  - Comparison of photodermatoses in African-Americans and Caucasians: a follow-up
      study.
AB  - BACKGROUND/PURPOSE: Only a few studies have compared frequencies of
      photodermatoses among different races and skin types. This is an extension of a
      study performed by Kerr and Lim and evaluates the frequency of photodermatoses in
      African-Americans compared with Caucasians in the same institution during an 8
      year period. METHODS: Retrospective chart review was performed, including
      dermatology clinic charts from October 2004 to August 2012 with International
      Classification of Diseases, Ninth Revision diagnostic codes related to
      photodermatoses. RESULTS: We identified 229 patients with photodermatoses. Of
      these, 138 (46.6%) were African-American and 63 (42.2%) were Caucasian.
      Statistically significant differences in the distribution of photodermatoses in
      African-Americans and Caucasians, respectively, were as follows: phototoxic drug
      eruption (0.7% and 15.9%, P < 0.0001), phytophotodermatitis (0% and 6.3%, P =
      0.009), polymorphous light eruption (PMLE) (86.2% and 54%, P < 0.0001) and
      porphyrias (0% and 7.9%, P = 0.003). CONCLUSION: Combined with data from Kerr and
      Lim, this is the largest study of photodermatoses in African-Americans to date.
      Congruent to former studies, photodermatoses do occur regularly in dark-skinned
      individuals. Overall, the frequency of photodermatoses in African-Americans and
      Caucasians are similar; however, PMLE occurs more commonly in African-Americans,
      and porphyias and phototoxicity occur more commonly in Caucasians.

PMID- 24118607
TI  - Changing clinical practice: management of paediatric community-acquired
      pneumonia.
AB  - RATIONALE AND AIM: To compare clinical features and management of paediatric
      community-acquired pneumonia (PCAP) following the publication of UK pneumonia
      guidelines in 2002 with data from a similar survey at the same hospitals in 2001
      2002 (pre-guidelines). METHODS: A prospective survey of 11 hospitals in Northern
      England was undertaken during 2008-2009. Clinical and laboratory data were
      recorded on children aged <=16 years who presented with clinical and radiological
      features of pneumonia. RESULTS: 542 children were included. There was a reduction
      in all investigations performed (P < 0.001) except C-reactive protein (P = 0.448)
      between surveys. These included full blood count (76% to 61%); blood culture (70%
      to 53%) and testing of respiratory secretions for viruses (24% to 12%) and
      bacteria (18% to 8%). Compared to pre-guidelines, there was a reduction in the
      use of intravenous antibiotics as a proportion of the total prescribed from 47%
      to 36% (P < 0.001) and a change in the route of antibiotic administration with
      increasing preference for oral alone (16% pre-compared to 50% post-guidelines, P
      < 0.001). CONCLUSION: Apart from the acute phase reactants that should not be
      measured routinely, these changes are in line with the guideline recommendations.
      Improvements in antibiotic use are possible and have implications for future
      antimicrobial stewardship programmes. Further work using cost-effectiveness
      analysis may also demonstrate a financial benefit to health services from
      adoption of guidelines.

PMID- 24118608
TI  - 'Touching people in relationships': a qualitative study of close relationships
      for people with an intellectual disability.
AB  - AIMS AND OBJECTIVES: To explore the experiences and perceptions of close and
      sexual relationships of people with an intellectual disability. BACKGROUND:
      Positive interpersonal relationships are beneficial for people with an
      intellectual disability, acting as a protective barrier against, social stigma
      and negative outcomes such as physical and mental health problems. The social
      networks of people with an intellectual disability are, however, often more
      restricted than those of the general population. There has been very little
      research exploring the views and experiences of people with an intellectual
      disability about social and sexual relationships. DESIGN: Exploratory study using
      a qualitative research design. METHODS: Semi-structured interviews were conducted
      with 10 (6 male, 4 female) participants. Data were analysed using interpretive
      phenomenological analysis. RESULTS: 'Touching other people in relationships' was
      identified as a superordinate theme. The theme was represented by five subthemes:
      'Is wrong'; 'Unsafe to talk about'; 'Suggesting is safe'; 'No freedom or fun';
      and 'Being touched'. The findings presented are drawn from a larger qualitative
      study. CONCLUSIONS: The findings highlight the importance of touch and sexual
      behaviours in the close relationships of participants. Negative perceptions were
      observed to surround sexual behaviours. Rules and restrictions regarding physical
      contact were also described. RELEVANCE TO CLINICAL PRACTICE: Disseminating these
      findings may increase awareness of the importance of physical contact in the
      close relationships of people with an intellectual disability and promote
      positive support arrangements.

PMID- 24118609
TI  - LmHus1 is required for the DNA damage response in Leishmania major and forms a
      complex with an unusual Rad9 homologue.
AB  - Genotoxic stress activates checkpoint-signalling pathways leading to cell cycle
      arrest and DNA repair. In many eukaryotes, the Rad9-Hus1-Rad1 (9-1-1) checkpoint
      complex participates in the early steps of the DNA damage response to replicative
      stress and is a pivotal contributor to genome homeostasis. The remarkable genome
      plasticity of the protozoan Leishmania hints at a peculiar DNA metabolism in
      these ancient eukaryotes. Therefore, we set out to investigate the existence of
      homologues of the 9-1-1 components in Leishmania major and found that LmHus1 and
      LmRad9 are phylogenetically related to the 9-1-1 complex subunits from other
      eukaryotes. Altered levels of LmHus1 and LmRad9 affected the parasite ability to
      manage genotoxic stress and LmHus1-defficent cells were defective in controlling
      cell cycle progression in response to genotoxic stress. Upon DNA damage, LmHus1
      was recruited to the chromatin and colocalized with the single-stranded DNA
      binding protein LmRpa1. Also, LmHus1 interacted with LmRad9 to form a DNA damage
      responsive complex in vivo. Altogether, our data strongly indicate the
      participation of LmHus1, LmRad9 and LmRpa1 in the L. major DNA damage response
      and suggest their involvement in genome maintenance mechanisms. 

PMID- 24118610
TI  - Proteomic analysis of a rare urinary stone composed of calcium carbonate and
      calcium oxalate dihydrate: a case report.
AB  - The objective of the present study was to investigate the matrix protein of a
      rare urinary stone that contained calcium carbonate. A urinary stone was
      extracted from a 34-year-old male patient with metabolic alkalosis. After X-ray
      diffractometry and infrared analysis of the stone, proteomic analysis was carried
      out. The resulting mass spectra were evaluated with protein search software, and
      matrix proteins were identified. X-ray diffraction and infrared analysis
      confirmed that the stone contained calcium carbonate and calcium oxalate
      dihydrate. Of the identified 53 proteins, 24 have not been previously reported
      from calcium oxalate- or calcium phosphate-containing stones. The protease
      inhibitors and several proteins related to cell adhesion or the cytoskeleton were
      identified for the first time. We analyzed in detail a rare urinary stone
      composed of calcium carbonate and calcium oxalate dihydrate. Considering the
      formation of a calcium carbonate stone, the new identified proteins should play
      an important role on the urolithiasis process in alkaline condition. 

PMID- 24118611
TI  - Plant genetics and interspecific competitive interactions determine
      ectomycorrhizal fungal community responses to climate change.
AB  - Although the importance of plant-associated microbes is increasingly recognized,
      little is known about the biotic and abiotic factors that determine the
      composition of that microbiome. We examined the influence of plant genetic
      variation, and two stressors, one biotic and one abiotic, on the ectomycorrhizal
      (EM) fungal community of a dominant tree species, Pinus edulis. During three
      periods across 16 years that varied in drought severity, we sampled the EM fungal
      communities of a wild stand of P. edulis in which genetically based resistance
      and susceptibility to insect herbivory was linked with drought tolerance and the
      abundance of competing shrubs. We found that the EM fungal communities of insect
      susceptible trees remained relatively constant as climate dried, while those of
      insect-resistant trees shifted significantly, providing evidence of a genotype by
      environment interaction. Shrub removal altered the EM fungal communities of
      insect-resistant trees, but not insect-susceptible trees, also a genotype by
      environment interaction. The change in the EM fungal community of insect
      resistant trees following shrub removal was associated with greater shoot growth,
      evidence of competitive release. However, shrub removal had a 7-fold greater
      positive effect on the shoot growth of insect-susceptible trees than insect
      resistant trees when shrub density was taken into account. Insect-susceptible
      trees had higher growth than insect-resistant trees, consistent with the
      hypothesis that the EM fungi associated with susceptible trees were superior
      mutualists. These complex, genetic-based interactions among species (tree-shrub
      herbivore-fungus) argue that the ultimate impacts of climate change are both
      ecological and evolutionary.

PMID- 24118612
TI  - TCP3 interacts with R2R3-MYB proteins, promotes flavonoid biosynthesis and
      negatively regulates the auxin response in Arabidopsis thaliana.
AB  - TCP proteins belong to the plant-specific bHLH transcription factor family, and
      function as key regulators of diverse developmental processes. Functional
      redundancy amongst family members and post-transcriptional down-regulation by
      miRJAW of several TCP genes complicate their functional characterization. Here,
      we explore the role of TCP3 by analyzing transgenic plants expressing miRJAW
      resistant mTCP3 and dominant-negative TCP3SRDX. Seedlings and seeds of mTCP3
      plants were found to hyper-accumulate flavonols, anthocyanins and
      proanthocyanidins, whereas levels of proanthocyanidins were slightly reduced in
      TCP3SRDX plants. R2R3-MYB proteins control not only early flavonoid biosynthetic
      steps but also activate late flavonoid biosynthetic genes by forming ternary R2R3
      MYB/bHLH/WD40 (MBW) complexes. TCP3 interacted in yeast with R2R3-MYB proteins,
      which was further confirmed in planta using BiFC experiments. Yeast three-hybrid
      assays revealed that TCP3 significantly strengthened the transcriptional
      activation capacity of R2R3-MYBs bound by the bHLH protein TT8. Transcriptome
      analysis of mTCP3 and TCP3SRDX plants supported a role for TCP3 in enhancing
      flavonoid biosynthesis. Moreover, several auxin-related developmental
      abnormalities were observed in mTCP3 plants. Transcriptome data coupled with
      studies of an auxin response reporter and auxin efflux carriers showed that TCP3
      negatively modulates the auxin response, probably by compromising auxin transport
      capacity. Genetic experiments revealed that the chalcone synthase mutant tt4-11
      lacking flavonoid biosynthesis abrogated the auxin-related defects caused by
      mTCP3. Together, these data suggest that TCP3 interactions with R2R3-MYBs lead to
      enhanced flavonoid production, which further negatively modulates the auxin
      response. 

PMID- 24118613
TI  - Variation in costs of parasite resistance among natural host populations.
AB  - Organisms that can resist parasitic infection often have lower fitness in the
      absence of parasites. These costs of resistance can mediate host evolution during
      parasite epidemics. For example, large epidemics will select for increased host
      resistance. In contrast, small epidemics (or no disease) can select for increased
      host susceptibility when costly resistance allows more susceptible hosts to
      outcompete their resistant counterparts. Despite their importance for evolution
      in host populations, costs of resistance (which are also known as resistance
      trade-offs) have mainly been examined in laboratory-based host-parasite systems.
      Very few examples come from field-collected hosts. Furthermore, little is known
      about how resistance trade-offs vary across natural populations. We addressed
      these gaps using the freshwater crustacean Daphnia dentifera and its natural
      yeast parasite, Metschnikowia bicuspidata. We found a cost of resistance in two
      of the five populations we studied - those with the most genetic variation in
      resistance and the smallest epidemics in the previous year. However, yeast
      epidemics in the current year did not alter slopes of these trade-offs before and
      after epidemics. In contrast, the no-cost populations showed little variation in
      resistance, possibly because large yeast epidemics eroded that variation in the
      previous year. Consequently, our results demonstrate variation in costs of
      resistance in wild host populations. This variation has important implications
      for host evolution during epidemics in nature. 

PMID- 24118615
TI  - Nursing students' experiences of being video-recorded during examination in a
      fictive emergency care situation.
AB  - Promoting undergraduate nursing students' learning in simulated care can be
      achieved through dynamic scenario-based training sessions that are documented
      using simple video equipment. One valuable aspect of this kind of training is the
      subsequent reflective dialogue that takes place between the teacher and the
      students during the examination. The aim of the present paper is to describe
      bachelor nursing students' experiences of being video-recorded during an
      examination with a simulated patient in emergency care. The study was descriptive
      in design and used a qualitative approach with written answers to open-ended
      questions; 44 undergraduate nursing students participated. A latent content
      analysis resulted in three themes: (i) visualization might cause nervousness at
      first; (ii) visualization promotes dialogue and acknowledgement; and (iii)
      visualization promotes increased self-knowledge and professional growth. The
      conclusion is that video-recording is a good way for undergraduate nursing
      students to develop skills in emergency care situations and to understand their
      own actions; it might also help them increase their self-knowledge. 

PMID- 24118614
TI  - Invariant natural killer T cells in children with eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is an atopic disease characterized by
      eosinophilic inflammation in which dietary antigens (in particular, milk) play a
      major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in
      which overexpression of Th2 cytokines, particularly IL-13, play a major role;
      however, the cells responsible for IL-13 overexpression remain elusive. Th2
      cytokines are secreted following the ligation of invariant natural killer T cell
      receptors to sphingolipids (SLs). Sphingolipids (SLs) are presented via the CD1d
      molecule on the INKTs surface. Cow's milk-derived SL has been shown to activate
      iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce
      Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently
      unknown. OBJECTIVE: The aim of this study was to investigate the role of iNKTs
      and milk-SL in EoE. METHODS: Peripheral blood mononuclear cells (PBMCs) from 10
      children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C) and 16
      healthy controls (non-EoE) were measured ex vivo and then incubated with alpha
      galactosylceramide (alphaGal) and milk-SL. INKTs from peripheral blood (PB) and
      oesophageal biopsies were studied. RESULTS: EoE-A children had significantly
      fewer peripheral blood iNKTs with a greater Th2-response to alphaGal and milk-SM
      compared with iNKTs of EoE-C and non-EoE children. Additionally, EoE-A children
      had increased iNKT levels in oesophageal biopsies compared with EoE-C children.
      CONCLUSION: Milk-SLs are able to activate peripheral blood iNKTs in EoE-A
      children to produce Th2 cytokines. Additionally, iNKT levels are higher at the
      site of active oesophageal eosinophilic inflammation. CLINICAL RELEVANCE: This
      study suggests that sphingolipids (SLs) contained in milk may drive the
      development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response
      that facilitates eosinophil-mediated allergic inflammation.

PMID- 24118616
TI  - Acid reflux episodes sensitize the esophagus to perception of weakly acidic and
      mixed reflux in non-erosive reflux disease patients.
AB  - BACKGROUND: Non-erosive reflux disease (NERD) patients are more sensitive than
      erosive esophagitis patients to weakly acidic reflux and to the presence of gas
      in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors
      to mechanical and chemical stimuli. METHODS: To establish whether acid
      sensitization plays a role in the perception of weakly acidic and mixed reflux
      episodes, 29 NERD patients, responders and 14 non-responders to proton pump
      inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the
      study while on PPIs. To assess the effect of acid exposure on symptom perception,
      the time period with pH below 4 was measured in 15- and 30-minute time-windows
      preceding the onset of each reflux episode. KEY RESULTS: Considering weakly
      acidic and mixed refluxes, both in responder and non-responder patients (off
      PPIs), the symptomatic refluxes were preceded by a significantly higher
      cumulative acid exposure than the asymptomatic refluxes. In all patients,
      following acid reflux, the percentage of symptomatic weakly acidic reflux
      episodes was significantly higher than that of asymptomatic refluxes. Non
      responder patients, off-treatment, were characterized by a lower proportion of
      weakly acidic reflux and mixed reflux episodes. In the non-responder patients on
      PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher
      cumulative acid exposure. CONCLUSIONS & INFERENCES: In NERD patients, spontaneous
      acid reflux enhances subsequent reflux perception, regardless of acidity or
      liquid/mixed composition of episodes; in non-responder patients on PPIs, only the
      perception of mixed and weakly acidic reflux episodes seems to be mediated by a
      preceding acid exposure.

PMID- 24118617
TI  - Gender-specific anthropometric markers of adiposity, metabolic syndrome and
      visceral adiposity index (VAI) in patients with obstructive sleep apnea.
AB  - Obstructive sleep apnea often coexists with visceral adiposity and metabolic
      syndrome. In this study, we analysed gender-related differences in
      anthropometrics according to sleep apnea severity and metabolic abnormalities. In
      addition, the visceral adiposity index, a recently introduced marker of
      cardiometabolic risk, was analysed. Consecutive subjects with suspected
      obstructive sleep apnea (n = 528, 423 males, mean age +/- standard deviation:
      51.3 +/- 12.8 years, body mass index: 31.0 +/- 6.2 kg m(-2) ) were studied by
      full polysomnography (apnea-hypopnea index 43.4 +/- 27.6 h(-1) ). Variables of
      general and visceral adiposity were measured (body mass index, neck, waist and
      hip circumferences, waist-to-hip ratio). The visceral adiposity index was
      calculated, and metabolic syndrome was assessed (NCEP-ATP III criteria). The
      sample included controls (apnea-hypopnea index <10 h(-1) , n = 55), and patients
      with mild-moderate (apnea-hypopnea index 10-30 h(-1) , n = 144) and severe sleep
      apnea (apnea-hypopnea index >30 h(-1) , n = 329). When anthropometric variables
      were entered in stepwise multiple regression, body mass index, waist
      circumference and diagnosis of metabolic syndrome were associated with the apnea
      hypopnea index in men (adjusted R(2)  = 0.308); by contrast, only hip
      circumference and height-normalized neck circumference were associated with sleep
      apnea severity in women (adjusted R(2)  = 0.339). These results changed little in
      patients without metabolic syndrome; conversely, waist circumference was the only
      correlate of apnea-hypopnea index in men and women with metabolic syndrome. The
      visceral adiposity index increased with insulin resistance, but did not predict
      sleep apnea severity. These data suggest gender-related interactions between
      obstructive sleep apnea, obesity and metabolic abnormalities. The visceral
      adiposity index was a good marker of metabolic syndrome, but not of obstructive
      sleep apnea. 

PMID- 24118618
TI  - Bacteroides fragilis concealed in an infant with Escherichia coli meningitis.
AB  - Anaerobic meningitis in infants is rare, therefore a high index of clinical
      suspicion is essential as routine methods for processing cerebrospinal fluid
      (CSF) do not detect anaerobes and specific antimicrobial therapy is required. We
      present an infant with Escherichia coli meningitis where treatment-resistance
      developed in association with culture negative purulent CSF. These features
      should have alerted us to the presence of anaerobes, prompting a search for the
      causes of polymicrobial meningitis in infants. 

PMID- 24118619
TI  - Impact factors of scientific journals: the new season.

PMID- 24118620
TI  - Foreseeing the future in infectious diseases: can we?

PMID- 24118622
TI  - Examining the relationship between relative age, competition level, and dropout
      rates in male youth ice-hockey players.
AB  - The relative age effect suggests that athletes born in the first two quartiles of
      a given selection year experience a selection advantage and therefore a greater
      opportunity for success. We describe two studies examining the relationship
      between relative age, competition level, and dropout rates of Ontario Minor
      Hockey Association male ice-hockey players from ages 10 to 15 years (n = 14 325).
      In Study 1, dropout was highest among players born in quartiles three and four
      [chi(2) (3) = 16.32, P < 0.05; w = 0.06], while Study 2 found dropped out players
      to have less movement between competition levels compared to retained players.
      This study confirms a relationship between relative age and dropout from ice
      hockey and adds further depth to our understanding of this persistent phenomenon.

PMID- 24118623
TI  - Making and using a mouse pad model of skin to practice suturing techniques.

PMID- 24118624
TI  - Avoidance-based human Pavlovian-to-instrumental transfer.
AB  - The Pavlovian-to-instrumental transfer (PIT) paradigm probes the influence of
      Pavlovian cues over instrumentally learned behavior. The paradigm has been used
      extensively to probe basic cognitive and motivational processes in studies of
      animal learning. More recently, PIT and its underlying neural basis have been
      extended to investigations in humans. These initial neuroimaging studies of PIT
      have focused on the influence of appetitively conditioned stimuli on instrumental
      responses maintained by positive reinforcement, and highlight the involvement of
      the striatum. In the current study, we sought to understand the neural correlates
      of PIT in an aversive Pavlovian learning situation when instrumental responding
      was maintained through negative reinforcement. Participants exhibited specific
      PIT, wherein selective increases in instrumental responding to conditioned
      stimuli occurred when the stimulus signaled a specific aversive outcome whose
      omission negatively reinforced the instrumental response. Additionally, a general
      PIT effect was observed such that when a stimulus was associated with a different
      aversive outcome than was used to negatively reinforce instrumental behavior, the
      presence of that stimulus caused a non-selective increase in overall instrumental
      responding. Both specific and general PIT behavioral effects correlated with
      increased activation in corticostriatal circuitry, particularly in the striatum,
      a region involved in cognitive and motivational processes. These results suggest
      that avoidance-based PIT utilizes a similar neural mechanism to that seen with
      PIT in an appetitive context, which has implications for understanding mechanisms
      of drug-seeking behavior during addiction and relapse. 

PMID- 24118625
TI  - Association of vascular access type with inflammatory marker levels in
      maintenance hemodialysis patients.
AB  - Aggressive NIH is a common histopathological lesion found at the sites of venous
      stenosis in arteriovenous fistula (AVF) and arteriovenous grafts (AVG).
      Inflammatory mediators have been proposed to play a pathogenic role in NIH, but
      there is paucity of data evaluating this hypothesis in clinical studies or in
      animal models. Serum levels of inflammatory mediators can potentially identify
      patients at high risk of AVF and AVG dysfunction. In a cross-sectional cohort
      study of 754 HD patients who were part of the NIED study cohort, we examined the
      associations between inflammatory markers including serum interleukin (IL) 1beta,
      IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) and
      type of vascular access. Unadjusted and multivariate-adjusted linear regression
      models were used. In addition, time-dependent regression model was used to assess
      the association between inflammatory markers and mortality. We observed that in
      the multivariate-adjusted model, inflammatory mediators interleukin-6 (IL-6),
      interleukin-1L-beta (IL-1beta), and C-reactive protein (CRP), the predicted value
      in hemodialysis patients, are lowest in patients with AVF and highest in central
      venous catheter (CVC) and AVG even in case-mix and malnutrition-inflammation
      complex syndrome (MICS)-adjusted models. IL-6 and CRP levels fall consistently in
      the same patients when AVG or CVC is changed to AVF and increase if the same
      patient changes access from AVF to AVG or CVC. Obesity is a risk factor for
      fistula failure and fistulas are associated with the lowest mortality compared
      with CVC and AVG. We did not find any statistically significant association
      between tumor necrosis factor-alpha (TNF- alpha) and vascular access outcomes.
      Higher levels of inflammatory mediators seen in CVC and AVG compared with AVF
      could potentially explain the higher mortality seen in patients with CVC and AVG
      compared with AVF. 

PMID- 24118626
TI  - IFNL3 (IL28B) polymorphism does not predict long-term response to interferon
      therapy in HBeAg-positive chronic hepatitis B patients.
AB  - The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN)
      treatment in patients infected with hepatitis B virus (HBV) is controversial. We
      aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long
      term response of chronic hepatitis B (CHB) treatment to conventional IFN. DESIGN:
      Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this
      study. Associations were investigated between IFNL3 genotypes and (i) HBeAg
      seroconversion at the end of treatment (EOT), (ii) sustained virological response
      (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients
      were followed for a median of 14 years. The majority of patients were infected
      with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were
      genotyped at rs12979860. Similar IFNL3 distribution was observed among the
      different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70).
      Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion
      rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively
      (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9
      and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80).
      HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion
      rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively
      (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis
      stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR,
      nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg
      positive CHB patients responding to IFN therapy.

PMID- 24118627
TI  - Promotional effect of platelet-rich plasma on hair follicle reconstitution in
      vivo.
AB  - BACKGROUND: Platelet-rich plasma (PRP) containing various growth factors has
      attracted attention in various medical fields. PRP has recently been used during
      hair transplantation to increase hair density. OBJECTIVE: To investigate the
      effects of PRP on hair follicle (HF) reconstitution. METHODS AND MATERIALS:
      Freshly isolated epidermal cells and cultured dermal papilla cells (DPCs) were
      mixed with various concentrations of activated PRP and transferred to a grafting
      chamber that was implanted onto the dorsal skin of nude mice. The chambers were
      removed 1 week after grafting, and HF formation was monitored for 4 weeks.
      RESULTS: We observed a significant difference (p < .05) in the number of newly
      formed follicles in the area of reconstituted skin (344 +/- 27 with 10% PRP vs
      288 +/- 35 without PRP). PRP also shortened the time of hair formation
      significantly; the first hairs were observed in 18 +/- 1 days using 10% PRP,
      versus 20 +/- 1 days without PRP. CONCLUSION: A considerable effect of PRP on the
      time of hair formation and the yield of HF reconstitution was observed in this
      study. Considering the limited evidence available to judge its efficacy, further
      studies are required to investigate the mechanism of action of PRP.

PMID- 24118628
TI  - Effect of physical effectiveness on digestibility of ration for cows in early
      lactation.
AB  - A study was conducted to investigate the effects of a diet particle size on
      nutrient digestibility in cows in early lactation. Treatments were diets with
      forage to concentrate ratio 43:57% in diet dry matter, with four different
      physically effective fibres (peNDF) content based on different cut length of corn
      silage and alfalfa haylage. The physical effectiveness factors (pef) and peNDF
      content of TMRs (total mixed ration) were determined using Penn State Particle
      Separator (PSPS) with two (pef8.0 , peNDF8.0) or three (pef1.18, peNDF1.18)
      sieves. The reducing of cut length of forages and particle size of diets did not
      affect on dry matter intake, while decreased peNDF intake by 16.34 and 8.83%, for
      peNDF8.0 and peNDF1.18 respectively. Apparent total tract digestibility of the
      nutrients was measured using two indicators: acid insoluble ash (AIA) and acid
      detergent insoluble lignin (ADL). Decreasing of forages cut length significantly
      increased apparent total tract digestibility of neutral detergent fibre (NDF)
      from 48.39% to 53.84% and from 53.9% to 58.66%, of crude protein from 73.96% to
      79.24% and from 71.56% to 77.90%, with contemporary decreasing of non-fibre
      carbohydrate from 90.89% to 84.81% and from 91.99% to 86.80%, with AIA or ADL as
      indicator respectively. Dietary value of net energy for lactation (NEL) and
      energy intake was not affected by the peNDF content of the diet.

PMID- 24118629
TI  - Needs and experiences of intensive care patients' families: a Saudi qualitative
      study.
AB  - AIM: To identify the perceived needs of Saudi families of patients in Intensive
      Care in relation to their culture and religion. BACKGROUND: Admission of a family
      member to an intensive care unit (ICU) is a deeply distressing and often
      unexpected life event to the family. Families of critically ill patients have
      needs that should be acknowledged and met by the ICU team. Literature is
      virtually silent on the issue of recognizing the ICU family needs in relation to
      the influence of their cultural values and religious beliefs. DESIGN: A
      descriptive exploratory qualitative study. METHOD: Individual, semi-structured
      interviews of a purposive sample of 12 family members were carried out between
      November 2011 and February 2012. The closest family members were recruited to
      participate in the interviews with a mean age of 44.25 years in eight mixed
      medical-surgical ICUs of eight major trauma hospitals in Saudi Arabia. RESULTS:
      The family needs and experiences are described via six major themes: looking for
      information, maintaining reassurance, spiritual healing, maintaining close
      proximity, involvement in care and support not being facilitated. The results
      indicated that family members sought to access information readily to diminish
      their anxiety. They also needed to be reassured that the best care was being
      delivered to their loved one and to feel supported during this critical time.
      Saudi families have cultural and spiritual healing beliefs and practices
      including faith in God and that God is the ultimate healer, reading of the
      Qur'an, prayer and charity. These lessen their stress and connect them to hold on
      to hope. In addition, maintaining proximity to their ill family member was
      considered of the greatest importance to the families. CONCLUSION: The study
      provided an in-depth understanding of the family members' experience of having a
      relative in Intensive Care and focussed on a range of unmet needs, particularly
      those related to culture and religion. The ICU team need to work collaboratively
      with family members to improve their experience. RELEVANCE TO PRACTICE: The
      recognition of family needs, experiences and situations can enhance the care
      provided by the critical care team to patients and families.

PMID- 24118630
TI  - Prosthodontic considerations in the implant-supported all-ceramic restoration of
      congenitally missing maxillary lateral incisor: a clinical report.
AB  - The congenitally missing maxillary lateral incisor is the most common agenesis in
      the anterior region. There are several treatment options for this anomaly, which
      causes severe deficiencies: orthodontic space closure, tooth-supported
      restoration, or single-tooth implant. Each of these solutions has a high degree
      of success if used in the correct situation. An implant-supported restoration
      with an interdisciplinary approach provides a predictable outcome. This article
      describes the treatment of a patient with agenesis of the maxillary left lateral
      incisor. After orthodontic space management, it was decided to restore the tooth
      with an all-ceramic crown cemented on a zirconia custom abutment, which fractured
      after only 6 weeks of service. Fractographic analysis revealed that the failure
      was due to over-reduction of the buccal wall to correct the labial emergence of
      the implant. Zirconia abutments should be designed with even wall thicknesses of
      at least 0.8 mm to avoid areas that may compromise functional success. 

PMID- 24118631
TI  - Medical specialists' views on the impact of reducing alcohol consumption on
      prognosis of, and risk of, hospital admission due to specific medical conditions:
      results from a Delphi survey.
AB  - RATIONALE, AIMS AND OBJECTIVES: To find consensus, or lack thereof, on the impact
      of reducing alcohol consumption on prognosis and the risk of hospital admissions
      for a number of alcohol-attributable disorders. METHODS: A modified two-round
      Delphi survey utilizing web-based questionnaires to collect quantitative and
      qualitative data was used. Alcohol treatment experts from cardiology, emergency
      medicine, gastroenterology and oncology in the United Kingdom were invited to
      participate. The main outcomes were median impact ratings (on a scale of 1-9) and
      consensus (unanimous, strong, moderate, weak or no consensus). RESULTS: Of 192
      experts invited to participate, 59 completed first questionnaires. The overall
      retention rate to the second questionnaires was about 51% (30/59). There was
      strong support that reducing alcohol consumption could result in improvement in
      prognosis for gastroenterology and emergency medicine patients; but uncertainty
      on the benefits for cardiology and oncology patients. Overall, the responses from
      the expert panel did not reflect the assumption that reducing alcohol consumption
      would result in benefits on hospital admissions for any of the specialties. The
      specialists viewed the severity of disorders as important when considering the
      impact of reducing alcohol consumption. CONCLUSIONS: The highest impact of
      treatment for problem drinking in hospitals is considered to be for alcohol
      related disorders associated with gastroenterology and emergency medicine. At
      policy level, if targeted screening for alcohol problems by presenting disease or
      condition is the strategy of choice, it would be logical to implement screening
      and easily accessible interventions or addiction specialists within these areas
      where alcohol treatment is considered as having a high impact.

PMID- 24118632
TI  - Women's experiences of sexual health after first-time myocardial infarction.
AB  - AIMS AND OBJECTIVES: To investigate women's experience of sexual problems after a
      myocardial infarction. BACKGROUND: Sexual problems among female patients with
      ischaemic heart disease have received little study but have been found to be
      highly prevalent in the research. Sexual problems have been found to influence
      quality of life and well-being, and sexual dysfunction has been associated with
      anxiety and depression. International guidelines recommend that healthcare
      professionals address sexuality; however, this is rarely done in practice, due to
      multiple causes, for example ignorance, embarrassment and lack of systematic
      treatment. Insight into women's sexual challenges after having a myocardial
      infarction is much needed. DESIGN: Qualitative interview study. METHODS:
      Qualitative interviews were conducted with 11 patients representative of the
      population and later transcribed. The analysis was inspired by Ricoeur's theory
      of interpretation, which consists of three levels: naive reading, structured
      analysis, and critical interpretation and discussion. RESULTS: The overall
      finding that emerged regarding the women's sexual health was an anxious resuming
      of sexual activity. Four themes emerged: (1) the partner, (2) support, (3) the
      heart disease's influence on sex and (4) the relationship. CONCLUSION: The women
      experienced anxious resuming of sexual activity. The heart disease had influence
      on their sex life, and relationship with their partner could be affected. Some
      needed support from health professionals or their network to dare sexual activity
      again. RELEVANCE TO CLINICAL PRACTICE: This study indicates that health
      professionals should focus more on identifying anxiety and exhaustion after
      myocardial infarction and articulating their potential influence on women's
      sexual lives. Whether this should be addressed in the hospital setting, in the
      phase 2 rehabilitation at the general practitioner level or in combination has to
      be considered and may be the basis for further research.

PMID- 24118633
TI  - Partial nephrectomy versus radical nephrectomy for non-metastatic pathological
      T3a renal cell carcinoma: a multi-institutional comparative analysis.
AB  - OBJECTIVES: To compare the recurrence-free survival of partial nephrectomy and
      radical nephrectomy in patients with non-metastatic pathological T3a renal cell
      carcinoma. METHODS: We reviewed the records of 3567 patients who had undergone a
      nephrectomy for renal cell carcinoma at five institutions in Korea from January
      2000 to December 2010. The clinical data of 45 patients with pathological T3a
      renal cell carcinoma in the partial nephrectomy group were compared with 298
      patients with pathological T3a renal cell carcinoma in the radical nephrectomy
      group. The effects of surgical methods on recurrence-free survival were assessed
      by a multivariate Cox proportional hazard analysis. All comparisons were repeated
      in subgroup analysis on 63 clinical T1a patients with tumors <=4 cm. RESULTS:
      During a median 43-month follow-up period, disease recurrence occurred in two
      patients (4.4%) in the partial nephrectomy group, and 94 patients (31.5%) in the
      radical nephrectomy group. The results from a multivariate model showed that
      radical nephrectomy was a significant predictor of recurrence. However, in
      subgroup analysis that included 63 clinical T1a pathological T3a patients, the
      recurrence-free survival rates were not significantly different between the two
      cohorts. The renal function was significantly better preserved in the partial
      nephrectomy cohort than in the radical nephrectomy cohort. CONCLUSIONS: Partial
      nephrectomy provides similar recurrence-free survival outcomes compared with
      radical nephrectomy in patients with clinical T1a pathological T3a renal cell
      carcinoma. However, there seems to be a higher risk of recurrence for large
      pathological T3a tumors treated by radical nephrectomy compared with small tumors
      treated by partial nephrectomy. Thus, large tumors with the same pathological T3a
      renal cell carcinoma grade could have hidden aggressive features.

PMID- 24118634
TI  - Vision, quality of life and depressive symptoms after first eye cataract surgery.
AB  - BACKGROUND: Cataract affects not only vision, but also performance of everyday
      tasks, participation in social activities, quality of life and possibly
      depression. Depression is a major health issue for older adults. It is estimated
      that 6%-20% of community-dwelling older Australians experience depression. The
      aim of this study was to investigate changes in vision-related quality of life
      and depressive symptoms after first eye cataract surgery and to determine which
      visual measures affect the change in these outcomes. METHODS: In 2009 and 2010,
      99 participants with bilateral cataract were recruited. Visual measures including
      visual acuity, contrast sensitivity and stereopsis were assessed 1 week before
      and 12 weeks after first eye cataract surgery. Vision-related quality of life was
      measured using the 25-item National Eye Institute Visual Function Questionnaire.
      Depressive symptoms were assessed by the 20-item Center for Epidemiological
      Studies Depression Scale. Separate regression analyses were undertaken to
      determine the association between visual measures and changes in vision-related
      quality of life and depressive symptoms after first eye cataract surgery.
      RESULTS: Overall, vision-related quality of life improved after first eye
      cataract surgery. There was a small, non-clinically significant improvement in
      depressive symptoms after surgery. Improvement in vision-related quality of life
      after first eye cataract surgery was associated with improved contrast
      sensitivity in the operated eye (P < 0.001), whereas improvement in depressive
      symptoms after surgery was associated with improved stereopsis (P = 0.032).
      CONCLUSIONS: Contrast sensitivity and stereopsis, but not visual acuity, were
      significant factors affecting improvement in vision-related quality of life or
      depressive symptoms after first eye cataract surgery.

PMID- 24118635
TI  - Nurses' knowledge and attitudes on comfort nursing care for hospitalized
      patients.
AB  - To investigate the knowledge and attitudes of practicing nurses on comfort care
      for hospitalized patients, a survey was conducted in 311 registered nurses from a
      major teaching hospital. A total of 212 (68.1%) of the participants showed an
      adequate knowledge of comfort care. Participants who had 6 years or more working
      experience returned a higher mean scores on physiological and psychological
      aspects of comfort care (P < 0.05). The total scores were the highest among
      participants from intensive care unit and the lowest among participants from the
      oncology department. Although 282 (90.7%) participants were involved in comfort
      care, only 210 (67.5%) received formal hospital-based training in this practice.
      We conclude that there was a large difference in the knowledge between nurses
      from different departments on comfort care. Continuing education programmes are
      required to improve the knowledge and skills in comfort care.

PMID- 24118636
TI  - Protection against hepatitis E virus infection by naturally acquired and vaccine
      induced immunity.
AB  - Immunity acquired from infection or vaccination protects humans from symptomatic
      hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is
      reduced by the immunity remains unknown. To understand this issue, a cohort with
      12 409 participants randomized to receive the hepatitis E vaccine Hecolin((r)) or
      placebo were serologically followed up for 2 years after vaccination. About half
      (47%) of participants were initially seropositive. A total of 139 infection
      episodes, evidenced by four-fold or greater rise of anti-HEV level or positive
      seroconversion, occurred in participants who received three doses of treatment.
      Risk of infection was highest among the baseline seronegative placebo group
      participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower
      the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both
      vaccine-induced and naturally acquired immunity can effectively protect against
      HEV infection.

PMID- 24118637
TI  - Systematic review of montelukast's efficacy for preventing post-bronchiolitis
      wheezing.
AB  - Infants often develop reactive airway diseases subsequent to respiratory
      syncytial virus (RSV) bronchiolitis. Cysteinyl leukotrienes (cysLTs), a class of
      lipid mediators that have been implicated in the pathogenesis of allergic
      rhinitis and asthma, are released during RSV infection, thereby contributing to
      the pathogenic changes in airway inflammation. Many pediatric patients,
      especially those of very young age, continue to have recurrent episodes of lower
      airway obstruction after bronchiolitis treatment. This study was to
      systematically review and assessed the efficacy of montelukast for preventing
      wheezing in patients with post-bronchiolitis. The Cochrane library, PubMed, China
      National Knowledge Infrastructure (CNKI) periodical databases were screened for
      studies related to use of montelukast for preventing post-bronchiolitis wheezing
      published up to 31 December 2012. Randomized controlled trials (RCTs) and quasi
      RCTs using montelukast alone as an active intervention in infants up to 24 months
      of age with post-bronchiolitis were selected. Two authors independently extracted
      data and assessed trial quality using the recommendations published by the
      Cochrane Collaboration. The meta-analyses were performed using the Cochrane
      statistical package RevMan5.0.0. Four trials, containing 1430 infants with
      confirmed diagnosis of acute bronchiolitis, were analyzed. Patients were
      administered montelukast at post-bronchiolitis. Three trials showed no effects of
      montelukast on reducing the incidence of recurrent wheezing risk ratios (RR =
      0.78, 95% CI: 0.55-1.12, p = 0.17), while two trials found that montelukast did
      reduce the frequency of recurrent wheezing and another two trials demonstrated no
      effects of montelukast on symptom-free days. The pooled montelukast treatment
      group showed no significant effect on reducing the usage of corticosteroids, as
      compared to the placebo group (RR = 1.11, 95% CI: 0.85-1.44, p = 0.45). Two
      trials showed that montelukast significantly decreased serum eosinophil-derived
      neurotoxin levels, as compared to the control group. In general, the side effects
      of rash, vomiting, and insomnia caused by montelukast occurred in 1.5% of
      patients analyzed. The recent evidences indicate that montelukast may reduce the
      frequency of post-bronchiolitic wheezing without causing significant side effects
      but that it has no effects on decreasing incidences of recurrent wheezing,
      symptom-free days, or the associated usage of corticosteroid in post
      bronchiolitis patients. The small number of enrolled participants and the
      inability to pool all clinical outcomes precludes us from making solid
      recommendations. 

PMID- 24118638
TI  - SUPPRESSOR OF LLP1 1-mediated C-terminal processing is critical for CLE19 peptide
      activity.
AB  - Cell-to-cell communication is essential for the coordinated development of
      multicellular organisms. Members of the CLAVATA3/EMBRYO-SURROUNDING REGION
      RELATED (CLE) family, a group of small secretory peptides, are involved in these
      processes in plants. Although post-translational modifications are considered to
      be indispensable for their activity, the detailed mechanisms governing these
      modifications are not well understood. Here, we report that SUPPRESSOR OF LLP1 1
      (SOL1), a putative Zn2+ carboxypeptidase previously isolated as a suppressor of
      the CLE19 over-expression phenotype, functions in C-terminal processing of the
      CLE19 proprotein to produce the functional CLE19 peptide. Newly isolated sol1
      mutants are resistant to CLE19 over-expression, consistent with the previous
      report (Casamitjana-Martinez, E., Hofhuis, H.F., Xu, J., Liu, C.M., Heidstra, R.
      and Scheres, B. (2003) Curr. Biol. 13, 1435-1441). As expected, our experiment
      using synthetic CLE19 peptide revealed that the sol1 mutation does not compromise
      CLE signal transduction pathways per se. SOL1 possesses enzymatic activity to
      remove the C-terminal arginine residue of CLE19 proprotein in vitro, and SOL1
      dependent cleavage of the C-terminal arginine residue is necessary for CLE19
      activity in vivo. Additionally, the endosomal localization of SOL1 suggests that
      this processing occurs in endosomes in the secretory pathway. Thus, our data
      indicate the importance of C-terminal processing of CLE proproteins to ensure CLE
      activities.

PMID- 24118639
TI  - Extra-group mating increases inbreeding risk in a cooperatively breeding bird.
AB  - In many cooperatively breeding species, females mate extra-group, the adaptive
      value of which remains poorly understood. One hypothesis posits that females
      employ extra-group mating to access mates whose genotypes are more dissimilar to
      their own than their social mates, so as to increase offspring heterozygosity. We
      test this hypothesis using life history and genetic data from 36 cooperatively
      breeding white-browed sparrow weaver (Plocepasser mahali) groups. Contrary to
      prediction, a dominant female's relatedness to her social mate did not drive
      extra-group mating decisions and, moreover, extra-group mating females were
      significantly more related to their extra-group sires than their social mates.
      Instead, dominant females were substantially more likely to mate extra-group when
      paired to a dominant male of low heterozygosity, and their extra-group mates
      (typically dominants themselves) were significantly more heterozygous than the
      males they cuckolded. The combined effects of mating with extra-group males of
      closer relatedness, but higher heterozygosity resulted in extra-group-sired
      offspring that were no more heterozygous than their within-group-sired half
      siblings. Our findings are consistent with a role for male-male competition in
      driving extra-group mating and suggest that the local kin structure typical of
      cooperative breeders could counter potential benefits to females of mating extra
      group by exposing them to a risk of inbreeding. 

PMID- 24118640
TI  - Initial combination of linagliptin and metformin in patients with type 2
      diabetes: efficacy and safety in a randomised, double-blind 1-year extension
      study.
AB  - OBJECTIVE: To determine the efficacy and safety of linagliptin in initial
      combination with metformin in patients with type 2 diabetes. METHODS: This 1-year
      randomised, double-blind study was an extension of a 6-month randomised
      controlled trial, in which adults with type 2 diabetes received one of six
      treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5
      mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid,
      linagliptin 5 mg qd or placebo). In the extension, patients in the first three
      treatment groups continued their regimen (non-switched group, n = 333) while the
      metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised
      to one of the three continuing regimens (switched group, n = 233). RESULTS: All
      three non-switched groups maintained reductions in glycosylated haemoglobin
      (HbA1c; mean +/- standard deviation reductions across the 1.5-year period:
      linagliptin 2.5 plus metformin 1000 bid, -1.63 +/- 1.05%; linagliptin 2.5 plus
      metformin 500 bid, -1.32 +/- 1.06%; metformin 1000 bid, -1.25 +/- 0.91%) while
      the switched groups showed additional HbA1c reductions. During the extension,
      there were no clinically meaningful changes in body weight in any group. Adverse
      event rates were similar between groups, with most events being mild or moderate,
      and the incidence of investigator-defined hypoglycaemia was low, with no severe
      events. DISCUSSION: Initial combination of linagliptin and metformin was well
      tolerated over the 1-year extension period, with low risk of hypoglycaemia, and
      improved glycaemic control vs. metformin alone. CONCLUSION: The initial
      combination of linagliptin and metformin appears to provide a useful treatment
      option in patients whose blood glucose levels are increased to an extent that
      metformin monotherapy may not achieve treatment targets.

PMID- 24118641
TI  - Clonal diversity driven by parasitism in a freshwater snail.
AB  - One explanation for the widespread abundance of sexual reproduction is the
      advantage that genetically diverse sexual lineages have under strong pressure
      from virulent coevolving parasites. Such parasites are believed to track common
      asexual host genotypes, resulting in negative frequency-dependent selection that
      counterbalances the population growth-rate advantage of asexuals in comparison
      with sexuals. In the face of genetically diverse asexual lineages, this advantage
      of sexual reproduction might be eroded, and instead sexual populations would be
      replaced by diverse assemblages of clonal lineages. We investigated whether
      parasite-mediated selection promotes clonal diversity in 22 natural populations
      of the freshwater snail Melanoides tuberculata. We found that infection
      prevalence explains the observed variation in the clonal diversity of M.
      tuberculata populations, whereas no such relationship was found between infection
      prevalence and male frequency. Clonal diversity and male frequency were
      independent of snail population density. Incorporating ecological factors such as
      presence/absence of fish, habitat geography and habitat type did not improve the
      predictive power of regression models. Approximately 11% of the clonal snail
      genotypes were shared among 2-4 populations, creating a web of 17 interconnected
      populations. Taken together, our study suggests that parasite-mediated selection
      coupled with host dispersal ecology promotes clonal diversity. This, in return,
      may erode the advantage of sexual reproduction in M. tuberculata populations. 

PMID- 24118642
TI  - Is narrow-band imaging useful for histological evaluation of gastric mucosa
      associated lymphoid tissue lymphoma after treatment?
AB  - BACKGROUND AND AIM: Endoscopic diagnosis of stomach mucosa-associated lymphoid
      tissue (MALT) lymphoma is often difficult because few specific findings are
      indicated. Even when MALT lymphoma is suspected by endoscopy, it is still
      difficult to make a definitive diagnosis by biopsy because lymphoma cells
      sometimes distribute unevenly. We previously reported that a tree-like appearance
      (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI)
      magnifying endoscopy and it is valuable in the selection of an optimal biopsy
      site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the
      relationship between the response to eradication therapy and TLA in MALT
      lymphoma. METHODS: We retrospectively examined the clinical background,
      endoscopic findings, response to eradication therapy, and Helicobacter pylori
      infection status of 16 patients diagnosed with MALT lymphoma who were referred to
      our hospital from April 2007 to August 2012. The regimen for eradicationtherapy
      consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7
      days. RESULTS: TLA was found in 75% (12/16) and H. pylori infection in 75%
      (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In
      all complete regression (CR) patients after eradication treatment, the TLA
      finding had disappeared (100%); however, in the non-CR patients, TLA remained the
      same as before the eradication therapy (P=0.002). CONCLUSION: These results
      suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but
      also in the evaluation of the response to eradication therapy of MALT lymphoma of
      the stomach.

PMID- 24118643
TI  - Can I be a student again? How medical graduates make the decision to return to
      dental school prior to a career in oral and maxillofacial surgery.
AB  - INTRODUCTION: Oral and maxillofacial surgery (OMFS) trainees in the UK have
      traditionally completed their dental undergraduate studies prior to returning to
      medical school. Recently, there have been increasing numbers of medical graduates
      who return to dental school before embarking on OMFS specialist training. There
      is limited research into the career motivation within this group and little
      guidance on how they may integrate the dental undergraduate course into their
      postgraduate training path. This study aims to evaluate these factors in more
      detail. METHODS: Questionnaires and focus groups were used to evaluate prior
      surgical experience of qualified medics who return to dental school with the
      intention of pursuing a career in OMFS, along with the factors that affect the
      timing of their return to dental school. RESULTS: The average age of medical
      graduates entering dental school decreased during the study period. The average
      number of months each cohort of students spent as a practicing doctor prior to
      starting dentistry also reduced. Postgraduate experience in OMFS was highly
      variable, but the numbers of students who received alternative exposure to OMFS,
      such as undergraduate special study modules, medical school elective or taster
      weeks, increased. The key barriers that were carefully considered by these
      trainees before returning to university included the perceived increase in the
      length of training, trainees' prior surgical experience, financial implications
      and the impact on quality of life. CONCLUSIONS: A trainee's decision to return to
      study dentistry is a multifactorial process. Understanding when trainees decide
      to return to sit their dental degree is vital not only to provide guidance for
      future trainees but also to assist future workforce planning, thus aiding
      training, education and development within OMFS.

PMID- 24118644
TI  - Uterine artery pseudoaneurysm hidden behind septic abortion: pseudoaneurysm
      without preceding procedure.
AB  - Uterine artery pseudoaneurysm (UAP) can occur after cesarean section or traumatic
      delivery, usually manifesting as postpartum hemorrhage. Here we report a patient
      with UAP possibly caused by septic abortion. She had high fever and bleeding with
      positive urine pregnancy test. We diagnosed this condition as septic abortion.
      Ultrasound revealed an intrauterine echogenic mass and color Doppler revealed
      swirling blood flow within the mass. Contrast-enhanced computed tomography showed
      a heterogeneously enhanced intrauterine mass. Selective internal iliac artery
      angiography revealed contrast medium within the mass immediately after medium
      injection. Bilateral uterine artery embolization was performed, after which
      medium no longer accumulated in the uterus, and hemostasis was achieved,
      confirming the diagnosis as UAP. Antibiotic treatment ameliorated the infection
      and the uterine content was expelled and absorbed. UAP can occur even without
      preceding procedures and may manifest abortive, and not postpartum, hemorrhage.
      UAP may be hidden behind septic abortion. 

PMID- 24118645
TI  - Multiple squamous cell carcinomas after megavoltage electron beam radiation
      therapy.

PMID- 24118646
TI  - Infant wheeze: is asthma a possibility?
AB  - Most infant wheeze is not asthma. Nonetheless, infants are able to develop
      reversible airway obstruction with or without allergic sensitisation, and asthma
      does occur at this age. The many other causes of infant wheeze, however, make
      asthma more difficult to distinguish from the background 'noise'. Consideration
      of risk factors and clinical features can enable some infants to be given a
      provisional diagnosis and, if their symptoms are disabling, a cautious trial of
      asthma treatment. 

PMID- 24118647
TI  - Hepatitis C virus 5' untranslated region variability correlates with treatment
      outcome.
AB  - Hepatitis C virus (HCV) variability affects viral-host interactions. We analysed
      HCV 5'untranslated region (5'UTR) in sera and peripheral blood mononuclear cells
      (PBMC) from chronic hepatitis C patients undergoing antiviral treatment. We
      studied 139 patients treated with pegylated interferon and ribavirin. The primary
      endpoint was a sustained virological response (SVR) defined as negative HCV RNA
      level 24 weeks after the end of therapy. 5'UTR was analysed by single-strand
      conformational polymorphism (SSCP) and sequencing. The pretreatment SSCP pattern
      in serum and PBMC differed in 26 (18.7%) patients. During therapy, the SSCP
      pattern remained stable in 65 (60.8%) patients, number of bands declined in 16
      (15.0%), and in 18 (16.8%) patients, changes were qualified as 'shift' indicating
      change in band positions. In univariate analysis, there was a significant (P <=
      0.05) positive association between SVR and pretreatment serum and PBMC
      dissimilarities, initial viral load <10(6) IU/mL, IL-28B CC genotype of the
      rs12979860 single nucleotide polymorphism and change in the SSCP band pattern
      (either 'shift' or decline) In multivariable analysis, only low initial viral
      load, IL-28B genotype, and changes in the SSCP band pattern were independent
      factors associated with SVR. In conclusion, stability of 5'UTR correlated with
      infection persistence, while changes correlated with SVR.

PMID- 24118648
TI  - Lack of association between apolipoprotein E genotypes and cognitive performance
      in the non-demented elderly.
AB  - AIM: The epsilon4 alelle of the apolipoprotein E gene is known to be a key
      genetic risk factor for Alzheimer's disease and possibly for other neurological
      disorders. Some evidence in the literature indicates that the epsilon4 allele
      interferes with human cognition independently of chronological age and diagnosis
      of Alzheimer's disease. The present study investigated the correlation of allelic
      variants of apolipoprotein E with the cognitive performance of elderly
      individuals without apparent cognitive impairment. METHODS: This was a cross
      sectional analysis that included 213 non-demented elderly individuals (age >=60
      years) from the Brazilian Federal District. The analysis assessed the subjects
      for cognitive domains including short- and long-term episodic memory, processing
      speed, and attention and executive functions. Sociodemographic and other clinical
      characteristics were gathered and analyzed as covariates. RESULTS: Being
      sufficiently powered, the present study did not identify differential performance
      across apolipoprotein E genotypes. There was no influence of age, gender, marital
      status, schooling, depressive symptoms or use of central nervous system
      depressants when the analyses were controlled for such factors. CONCLUSIONS: Our
      findings suggest that the epsilon4 allele does not contribute to detectable
      cognitive decline within the context of non-dementia.

PMID- 24118649
TI  - Spatiotopic perceptual learning mediated by retinotopic processing and
      attentional remapping.
AB  - Visual processing takes place in both retinotopic and spatiotopic frames of
      reference. Whereas visual perceptual learning is usually specific to the trained
      retinotopic location, our recent study has shown spatiotopic specificity of
      learning in motion direction discrimination. To explore the mechanisms underlying
      spatiotopic processing and learning, and to examine whether similar mechanisms
      also exist in visual form processing, we trained human subjects to discriminate
      an orientation difference between two successively displayed stimuli, with a gaze
      shift in between to manipulate their positional relation in the spatiotopic frame
      of reference without changing their retinal locations. Training resulted in
      better orientation discriminability for the trained than for the untrained
      spatial relation of the two stimuli. This learning-induced spatiotopic preference
      was seen only at the trained retinal location and orientation, suggesting
      experience-dependent spatiotopic form processing directly based on a retinotopic
      map. Moreover, a similar but weaker learning-induced spatiotopic preference was
      still present even if the first stimulus was rendered irrelevant to the
      orientation discrimination task by having the subjects judge the orientation of
      the second stimulus relative to its mean orientation in a block of trials.
      However, if the first stimulus was absent, and thus no attention was captured
      before the gaze shift, the learning produced no significant spatiotopic
      preference, suggesting an important role of attentional remapping in spatiotopic
      processing and learning. Taken together, our results suggest that spatiotopic
      visual representation can be mediated by interactions between retinotopic
      processing and attentional remapping, and can be modified by perceptual training.

PMID- 24118650
TI  - Catalogue of knowledge and skills for sleep medicine.
AB  - Sleep medicine is evolving globally into a medical subspeciality in its own
      right, and in parallel, behavioural sleep medicine and sleep technology are
      expanding rapidly. Educational programmes are being implemented at different
      levels in many European countries. However, these programmes would benefit from a
      common, interdisciplinary curriculum. This 'catalogue of knowledge and skills'
      for sleep medicine is proposed, therefore, as a template for developing more
      standardized curricula across Europe. The Board and The Sleep Medicine Committee
      of the European Sleep Research Society (ESRS) have compiled the catalogue based
      on textbooks, standard of practice publications, systematic reviews and
      professional experience, validated subsequently by an online survey completed by
      110 delegates specialized in sleep medicine from different European countries.
      The catalogue comprises 10 chapters covering physiology, pathology, diagnostic
      and treatment procedures to societal and organizational aspects of sleep
      medicine. Required levels of knowledge and skills are defined, as is a proposed
      workload of 60 points according to the European Credit Transfer System (ECTS).
      The catalogue is intended to be a basis for sleep medicine education, for sleep
      medicine courses and for sleep medicine examinations, serving not only physicians
      with a medical speciality degree, but also PhD and MSc health professionals such
      as clinical psychologists and scientists, technologists and nurses, all of whom
      may be involved professionally in sleep medicine. In the future, the catalogue
      will be revised in accordance with advances in the field of sleep medicine. 

PMID- 24118651
TI  - Tetracycline accumulates in Iberis sempervirens L. through apoplastic transport
      inducing oxidative stress and growth inhibition.
AB  - Environmental antibiotic contamination is due mainly to improper and illegal
      disposal of these molecules that, yet pharmacologically active, are excreted by
      humans and animals. These compounds contaminate soil, water and plants. Many
      studies have reported the bioaccumulation of antibiotics in plants and their
      negative effects on photosynthesis, cell growth and oxidative balance. Therefore,
      the principal objective of this paper was the study of antibiotic accumulation
      sites in plants and its uptake modality. Iberis sempervirens L., grown in soil
      and in agar in the presence or absence of tetracycline, were used as a model
      system. Using confocal and transmission electron microscopy, we demonstrated that
      tetracycline was absorbed and propagated in plants through apoplastic transport
      and also accumulated in intercellular spaces. Tetracycline was rarely detected
      inside cells (in cytoplasm and mitochondria where, coherent to its
      pharmacological activity, it probably affected ribosomes), except in stomata.
      Moreover, we verified and clarified further the phytotoxic effects of
      tetracycline on plants. We observed that the antibiotic induced a large reduction
      in plant growth and development and inhibition of photosynthetic activity. As
      tetracycline may lead to oxidative stress in plants, plant cells tried to balance
      this disequilibrium by increasing the amount and activity of some endogenous
      enzyme antioxidant agents (superoxide dismutase 1 and catalase) and levels of
      antiradical secondary metabolites. 

PMID- 24118652
TI  - Recurrent reactions to food among children at paediatric emergency departments:
      epidemiology of allergic disease.
AB  - BACKGROUND: Knowledge about repeated food reactions in paediatric emergency
      departments (ED) is sparse. OBJECTIVE: To investigate the incidence and potential
      risk factors for repeated ED visits for food-allergic reactions among children
      with a prior ED visit due to reactions to food. METHODS: A total of 358 children
      with ED visits at paediatric hospitals in Stockholm due to reactions to foods
      during 2007 (index-reaction) were investigated in relation to recurrent reactions
      until 30 June 2010. Adjusted Cox proportional hazard models were used to compute
      relative risks (RR) and 95% confidence intervals (CI). RESULTS: A total of 80
      children had 116 ED revisits over a period of 873 patient-years, yielding an
      incidence rate of 9 per 100 patient-years. Known food allergy before the index ED
      visit in 2007 increased the risk for ED revisits (RR = 2.30, 95% CI 1.35-3.94).
      Likewise, prescription of adrenaline auto-injector before the index-reaction
      increased the risk (RR = 2.02, 95% CI 1.17-3.49). Twenty-one percent of the
      children had more severe reactions at the revisit, 38% less severe and 41% had
      reactions of comparable severity. However, among 44% of the children with
      comparable or less severe reaction at revisit, early treatment with adrenaline
      hampered the classification of change in severity. CONCLUSIONS AND CLINICAL
      RELEVANCE: Previously known food allergy and prior prescription of adrenaline are
      significant risk factors for ED revisits among children with a prior ED visit due
      to reactions to food. Our results indicate that the severity of the index
      reaction cannot be used to predict the severity of the relapse.

PMID- 24118653
TI  - Cystectomy and urinary diversion as management of treatment-refractory benign
      disease: the impact of preoperative urological conditions on perioperative
      outcomes.
AB  - OBJECTIVES: To investigate perioperative outcomes associated with cystectomy and
      urinary diversion for treatment-refractory benign urological disease. METHODS: A
      cohort of patients who underwent cystectomy for infection, fistula, bleeding,
      incontinence, neurogenic bladder or pain between January 2004 and June 2012 was
      established. Data included baseline demographics, indications for cystectomy and
      prior treatments, and complications at 30 and 90 days. Primary outcome measures
      were 30-day and 30 to 90-day complications. RESULTS: The study group comprised
      eight males and 18 females. The mean age was 57.8 years (95% CI 50.8-64.7). A
      total of 19 patients (73%) had resolution of their underlying urological
      pathology at 90 days. A total of 19 patients (73%) experienced a complication in
      the first 30 days, of which nine (47%) were Clavien grade III or higher. The most
      common 30-day complications were urinary tract infection (n = 6, 23%) and wound
      infection (n = 6, 23%). A total of 44% (4/9) of patients with neurogenic bladder
      experienced a complication within the first 30 days of cystectomy compared with
      100% (8/8) of patients with radiation-induced fistula (P = 0.03) and 78% (7/9) of
      non-neurogenic, non-radiation-induced fistula patients (P = 0.34). CONCLUSIONS:
      Cystectomy with urinary diversion for benign disease might be successful, but is
      associated with a high rate of perioperative complications. Those with radiation
      induced fistula are more likely to experience complications, whereas those with
      neurogenic bladder carry a lower risk. Patients should be counseled appropriately
      regarding expected postoperative outcomes.

PMID- 24118654
TI  - Principal component analysis of odor coding at the level of third-order olfactory
      neurons in Drosophila.
AB  - Olfactory information in Drosophila is conveyed by projection neurons from
      olfactory sensory neurons to Kenyon cells (KCs) in the mushroom body (MB). A
      subset of KCs responds to a given odor molecule, and the combination of these KCs
      represents a part of the neuronal olfactory code. KCs are also thought to
      function as coincidence detectors for memory formation, associating odor
      information with a coincident punishment or reward stimulus. Associative
      conditioning has been shown to modify KC output. This plasticity occurs in the
      vertical lobes of MBs containing alpha/alpha' branches of KCs, which is shown by
      measuring the average Ca(2+) levels in the branch of each lobe. We devised a
      method to quantitatively describe the population activity patterns recorded from
      axons of >1000 KCs at the alpha/alpha' branches using two-photon Ca(2+) imaging.
      Principal component analysis of the population activity patterns clearly
      differentiated the responses to distinct odors. 

PMID- 24118655
TI  - Visualization and live imaging analysis of a mosquito saliva protein in host
      animal skin using a transgenic mosquito with a secreted luciferase reporter
      system.
AB  - Mosquitoes inject saliva into a vertebrate host during blood feeding. The
      analysis of mosquito saliva in host skin is important for the elucidation of the
      inflammatory responses to mosquito bites, the development of antithrombotic
      drugs, and the transmission-blocking of vector-borne diseases. We produced
      transgenic Anopheles stephensi mosquitoes expressing the secretory luciferase
      protein (MetLuc) fused to a saliva protein (AAPP) in the salivary glands. The
      transgene product (AAPP-MetLuc) of transgenic mosquitoes exhibited both
      luciferase activity as a MetLuc and binding activity to collagen as an AAPP. The
      detection of luminescence in the skin of mice bitten by transgenic mosquitoes
      showed that AAPP-MetLuc was injected into the skin as a component of saliva via
      blood feeding. AAPP-MetLuc remained at the mosquito bite site in host skin with
      luciferase activity for at least 4 h after blood feeding. AAPP was also suspected
      of remaining at the site of injury caused by the mosquito bite and blocking
      platelet aggregation by binding to collagen. These results demonstrated the
      establishment of visualization and time-lapse analysis of mosquito saliva in
      living vertebrate host skin. This technique may facilitate the analysis of
      mosquito saliva after its injection into host skin, and the development of new
      drugs and disease control strategies. 

PMID- 24118656
TI  - Validation of the Essentials of Magnetism II in Chinese critical care settings.
AB  - AIMS: To translate and evaluate the psychometric properties of the Essentials of
      Magnetism II tool (EOM II) for Chinese nurses in critical care settings.
      BACKGROUND: The EOM II is a reliable and valid scale for measuring the healthy
      work environment (HWE) for nurses in Western countries, however, it has not been
      validated among Chinese nurses. METHODS: The translation of the EOM II followed
      internationally recognized guidelines. The Chinese version of the Essentials of
      Magnetism II tool (C-EOM II) was reviewed by an expert panel for culturally
      semantic equivalence and content validity. Then, 706 nurses from 28 intensive
      care units (ICUs) affiliated with 14 tertiary hospitals participated in this
      study. The reliability of the C-EOM II was assessed using the Cronbach's alpha
      coefficient; the content validity of this scale was assessed using the content
      validity index (CVI); and the construct validity was assessed using the
      confirmatory factor analysis (CFA). RESULTS: The C-EOM II showed excellent
      content validity with a CVI of 0.92. All the subscales of the C-EOM II were
      significantly correlated with overall nurse job satisfaction and nurse-assessed
      quality of care. The CFA showed that the C-EOM II was composed of 45 items with
      nine factors, accounting for 46.51% of the total variance. Cronbach's alpha
      coefficients for these factors ranged from 0.56 to 0.89. CONCLUSIONS: The C-EOM
      II is a promising scale to assess the HWE for Chinese ICU nurses. RELEVANCE TO
      CLINICAL PRACTICE: Nursing administrators and health care policy-makers can use
      the C-EOM II to evaluate clinical work environment so that a healthier work
      environment can be created and sustained for staff nurses.

PMID- 24118657
TI  - Damped long-term host-parasite Red Queen coevolutionary dynamics: a reflection of
      dilution effects?
AB  - An increase in biological diversity leads to a greater stability of ecosystem
      properties. For host-parasite interactions, this is illustrated by the 'dilution
      effect': a negative correlation between host biodiversity and disease risk. We
      show that a similar mechanism might stabilise host-parasite dynamics at a lower
      level of diversity, i.e. at the level of genetic diversity within host species. A
      long-term time shift experiment, based on a historical reconstruction of a
      Daphnia-parasite coevolution, reveals infectivity cycles with more stable
      amplitude in experienced than in naive hosts. Coevolutionary models incorporating
      an increase in host allelic diversity over time explain the detected asymmetry.
      The accumulation of resistance alleles creates an opportunity for the host to
      stabilise Red Queen dynamics. It leads to a larger arsenal enhancing the host
      performance in its coevolution with the parasite in which 'it takes all the
      running both antagonists can do to keep in the same place'. 

PMID- 24118659
TI  - Full-mouth rehabilitation of severely worn dentition due to soda swishing: a
      clinical report.
AB  - Diagnosis and treatment planning of severely worn dentition are complex and
      complicated. Erosion is one of the common causes of lost tooth surface. Defining
      the etiology of the erosion is essential before proceeding with treatment to be
      able to provide the most predictable treatment outcome. Multiple specialists
      including psychologists, family medicine practioners, and social workers should
      be involved in the diagnosis and the prevention of a continuing erosion process.
      The treatment plan should be based on the severity of the tooth surface lost. It
      can range from simple direct restorations to a full-mouth rehabilitation. This
      clinical report is a detailed description of a complex prosthodontic diagnostic
      index class IV patient based on current evidence-based dentistry. 

PMID- 24118658
TI  - Prevalence of colonic motor or evacuation disorders in patients presenting with
      chronic nausea and vomiting evaluated by a single gastroenterologist in a
      tertiary referral practice.
AB  - BACKGROUND: Nausea and vomiting are thought to result from upper gastrointestinal
      dysfunctions. Our clinical observations led to the hypothesis that colonic motor
      dysfunction is associated with nausea and vomiting. METHODS: We reviewed
      electronic medical records (EMR) of 149 patients presenting with complaints of
      nausea and/or vomiting in a tertiary gastroenterology practice to investigate the
      association with disorders of colonic motor or evacuation disorders. We extracted
      demographics, gastric emptying (GE in 149) and colonic transit (CT in 138) of
      solids, ascending colon emptying half-time (AC t1/2 ), rectal evacuation by
      anorectal manometry (ARM) in 91 and balloon expulsion test (BE) in 55 patients.
      We estimated the proportions with delayed GE or CT, based on the 5th percentile
      of GE (in 319) and CT in 220 healthy volunteers using same method. KEY RESULTS:
      Among 11 patients with nausea and/or vomiting with only GE measured, five had
      delayed and six normal GE. Among the 149 patients, 77 (52%) patients had
      evacuation disorders, confirmed by objective tests in 68 patients, and clinical
      examination in nine patients. In the 138 patients with both GE and CT measured,
      106 (76%) had both normal GE and CT, 11 (8%) only delayed GE, 16 (11%) normal GE
      with delayed CT, and five (3%) delayed GE and CT. Among 21 patients (15%) with
      delayed CT, nine had slow AC t1/2 and 12 evacuation disorder. CONCLUSIONS &
      INFERENCES: In patients with chronic nausea and/or vomiting in gastroenterology
      practice, evaluation of colonic motility and rectal evacuation should be
      considered, since about half the patients have abnormal functions that
      conceivably contribute to the presenting nausea and/or vomiting.

PMID- 24118660
TI  - Black truffle-associated bacterial communities during the development and
      maturation of Tuber melanosporum ascocarps and putative functional roles.
AB  - Although truffles are cultivated since decades, their life cycle and the
      conditions stimulating ascocarp formation still remain mysterious. A role for
      bacteria in the development of several truffle species has been suggested but few
      is known regarding the natural bacterial communities of Perigord Black truffle.
      Thus, the aim of this study was to decipher the structure and the functional
      potential of the bacterial communities associated to the Black truffle in the
      course of its life cycle and along truffle maturation. A polyphasic approach
      combining 454-pyrosequencing of 16S rRNA gene, TTGE, in situ hybridization and
      functional GeoChip 3.0 revealed that Black truffle ascocarps provide a habitat to
      complex bacterial communities that are clearly differentiated from those of the
      surrounding soil and the ectomycorrhizosphere. The composition of these
      communities is dynamic and evolves during the maturation of the ascocarps with an
      enrichment of specific taxa and a differentiation of the gleba and peridium
      associated bacterial communities. Genes related to nitrogen and sulphur cycling
      were enriched in the ascocarps. Together, these data paint a new picture of the
      interactions existing between truffle and bacteria and of the potential role of
      these bacteria in truffle maturation. 

PMID- 24118661
TI  - Comprehensive geriatric assessment--a guide for the non-specialist.

PMID- 24118662
TI  - The frequency of painful procedures in neonatal intensive care units in South
      Korea.
AB  - This study was to evaluate the performed painful procedures among all sick
      neonates cared for at two university hospital neonatal intensive care units
      (NICUs) in the Republic of Korea. This prospective study was done with all
      newborns admitted to the NICUs between 1 October and 20 November 2010. Data
      collection was done with self-administered questionnaire by each nurse for the
      first 2 weeks of admission and discontinued if the neonate was discharged,
      transferred or died. The number of painful procedures, according to general
      characteristics of the neonates, were compared using Mann-Whitney U-test and
      Kruskal-Wallis test. Oral suctioning was the most frequently performed procedure,
      followed by tracheal suctioning and nasal suctioning. The number of painful
      procedures increased as the gestation period became shorter and birthweight
      decreased. In conclusion, nurses should reappraise the need for painful
      procedures, in particular, among neonates with a gestation period of <= 27 weeks
      and babies with <= 1000 g of birthweight, and execute their performance only if
      necessary. 

PMID- 24118663
TI  - Nasolacrimal duct screening to minimize post-cataract surgery endophthalmitis.
AB  - BACKGROUND: To examine unrecognized nasolacrimal duct obstruction as a risk
      factor for developing endophthalmitis post-cataract surgery in order to assess
      the value of preoperative lacrimal system screening. DESIGN: Prospective case
      control study. PARTICIPANTS: A random sample of patients undergoing
      phacoemulsification cataract surgery (control group) and a consecutive series of
      patients admitted to our hospital with post-cataract surgery endophthalmitis.
      METHODS: We compared the rate of nasolacrimal duct obstruction in the control
      group versus the endophthalmitis series. Both groups underwent nasolacrimal duct
      syringing with normal saline on the ipsilateral side to the surgery. A standard
      macro-dacryocystogram was performed to confirm for obstruction detected on
      syringing. MAIN OUTCOME MEASURES: Nasolacrimal duct obstruction rate. RESULTS:
      Forty-four eyes from 39 patients were included in this study: 34 eyes from 29
      patients formed the control group and 10 eyes from 10 patients formed the
      endophthalmitis group. A higher rate of nasolacrimal duct obstruction was found
      among patients who developed endophthalmitis post-cataract in comparison with the
      control group, on both nasolacrimal duct syringing (50.0% vs. 11.8%; P = 0.018)
      and macro-dacryocystogram (20.0% vs. 2.9%, P = 0.125). Two out of the three
      patients with radiologically confirmed nasolacrimal duct obstruction reported a
      long history of epiphora. CONCLUSION: The higher rates of obstruction on
      nasolacrimal duct syringing and macro-dacryocystogram among patients who
      developed endophthalmitis suggest that nasolacrimal duct obstruction is a
      significant risk factor for postoperative endophthalmitis. We recommend routine
      screening for symptoms and examination of the lacrimal system prior to cataract
      surgery.

PMID- 24118664
TI  - Students' satisfaction with a dental summer programme and importance of
      influencing factors for choosing dentistry as their career.
AB  - AIM: To study the students' satisfaction with the week-long summer programme and
      the importance of common influencing factors (IFs) for choosing dentistry as
      their career. METHODS: Anonymous questionnaire was given to all 214 participants
      in July of 2011 and 2012. Demographic information including gender, age and
      education level was collected. The students were asked about their satisfaction
      with the programme with separate ratings for learning experiences, including
      hands-on workshops (HOW); clinic observations (CO); problem-based learning
      tutorials (PBL); and lectures (L). They also rated the relative importance of the
      ten common IFs. The Friedman test was used to study the order of their
      preferences of the programme's activities. The Chi-square test was used to study
      the influence of their demographic factors on the importance of the IFs. RESULTS:
      A total of 208 students returned their questionnaires. The majority were below
      the age of 18 (81%), and 44% were studying in an international school. Most of
      the students (96%) were satisfied with the programme overall. They liked the HOWs
      and COs more than the PBL tutorials and Ls. 'Altruism' and 'medical/health care
      career' were the two most important IFs overall. 'Altruism' and 'past experience
      with dentist' were considered more important by those aged 18 or above. 'Past
      experience with dentist' and 'working with hands' were considered more important
      by the international school students. CONCLUSIONS: Most participants were
      satisfied with the summer programme. They preferred practical, skill-based
      activities to knowledge-based activities. The importance of some IFs was
      associated with age and education system.

PMID- 24118665
TI  - Soluble CD163 masks fibronectin-binding protein A-mediated inflammatory
      activation of Staphylococcus aureus infected monocytes.
AB  - Binding to fibronectin (FN) is a crucial pathogenic factor of Staphylococcus
      aureus mediated by fibronectin-binding protein A (FnBP-A) and extracellular
      adherence protein (Eap). Recently, we have shown that binding of soluble CD163
      (sCD163) to FN linked to these molecules exhibits anti-microbial effects by
      enhancing phagocytosis and killing activity of S. aureus-infected monocytes.
      However, it remained unclear whether sCD163 also influences the monocytic
      activation status. Using genetically modified staphylococcal strains we now
      identified FnBP-A, but not Eap, as activator of the inflammatory response of
      monocytes to infection. FnBP-A-mediated inflammatory activation was masked by
      sCD163 binding to S. aureus promoting efficient pathogen elimination. Thus,
      sCD163 protects monocytes from overwhelming activation upon staphylococcal
      infection by dampening the secretion of pro-inflammatory cytokines TNFalpha, IL
      1beta, IL-6 and IL-8 and DAMP molecule MRP8/14. Moreover, sCD163 limited
      expression of pro-apoptotic transcription factor NR4A1 induced during S. aureus
      infection and inhibited induction of chemokine CXCL2promoting survival of
      staphylococci in vivo. sCD163-mediated effects were not due to general
      immunosuppression since MAP kinase activation and ROS production were unaltered
      during infection of monocytes with sCD163-bound bacteria. Thus, sCD163 promotes a
      specific defence of the immune system against FnBP-A-mediated inflammatory
      activation enabling successful pathogen elimination, tissue recovery and
      resolution of inflammation. 

PMID- 24118666
TI  - The role of founder effects on the evolution of reproductive isolation.
AB  - Several theories argue that large changes in allele frequencies through genetic
      drift after a small founding population becomes allopatrically isolated can lead
      to significant changes in reproductive isolation and thus trigger the origin of
      new species. For this reason, founder speciation has been proposed as a potent
      force in the generation of new species. Nonetheless, the relative importance of
      such 'founder effects' remains largely untested. In this report, I used
      experimental evolution to create one thousand replicates that underwent an
      extreme bottleneck and to study whether founder effects can lead to an increase
      in reproductive isolation in Drosophila yakuba. Even though the most common
      outcome of inbreeding is extinction, founder effects can lead to increased
      premating reproductive isolation in a very small proportion of cases. Changes in
      reproductive isolation after a founding population bottleneck are similar to
      changes in other phenotypic traits, in which inbreeding might displace the mean
      phenotypic value and substantially increase the phenotypic variance. This
      increase in phenotypic variance does not confer an increase in the response to
      selection for reproductive isolation in artificial selection experiments,
      indicating that the increased phenotypic variance is not caused by increases in
      additive genetic variance. These results also demonstrate that, similar to
      morphological and life-history traits, behavioural traits can be affected by
      inbreeding and genetic drift. 

PMID- 24118667
TI  - Phylogenetically related, clinically different: human papillomaviruses 6 and 11
      variants distribution in genital warts and in laryngeal papillomatosis.
AB  - Genital warts (GWs) and laryngeal papillomatosis (LP) are two usually benign
      pathologies related to infection with human papillomaviruses (HPVs), mainly HPV6
      and HPV11. The aim of this work was to describe the genetic diversity of HPV6 and
      HPV11 isolates found in GWs and LPs, and to analyse the differential involvement
      of viral variants in either lesion. A total of 231 samples diagnosed as GWs (n =
      198) or LP (n = 33) and caused by HPV6 or HPV11 monoinfections were analysed. The
      phylogenetic relationships of the retrieved viral sequences were explored. We
      have identified the long control region and the intergenic E2-L2 region as the
      two most variable regions in both HPV6 and HPV11 genomes. We have generated new
      HPV6 (n = 166) or HPV11 (n = 65) partial sequences from GWs and LPs lesions
      spanning both regions and studied them in the context of all available sequences
      of both types (final n = 412). Our results show a significant (p <0.01)
      differential presence of HPV6 variants among both pathologies, with HPV6 B
      variants being preferentially found in GW versus LP samples. No differential
      involvement of HPV11 variants was observed. Our findings suggest that different
      HPV6 variants may either show differential tropism or have different potential to
      induce lesions in different epithelia.

PMID- 24118669
TI  - 'Out of the mouth of babes'--lessons in immunology.

PMID- 24118670
TI  - Drager VN500's oscillatory performance has a frequency-dependent threshold.
AB  - AIM: The aim of this study is to compare the high-frequency pressure amplitude
      (oscillatory change in pressure (DeltaP)) and tidal volume (high-frequency tidal
      volume at the airway opening (VTHF )) delivered by the Drager VN500 (Dragerwerk
      Ag & Co., Lubeck, Germany) and the Sensormedics 3100 (SM3100; CareFusion, San
      Diego, CA, USA) through a range of oscillatory frequencies. METHODS: In this
      benchtop study, high-frequency oscillations were applied to an infant test lung
      at unrestricted set amplitudes. Pressure and flow were measured as a function of
      frequency, incremented by 1 Hz from 5 to 15 Hz. Measurements were repeated for a
      range of ventilator settings, and lung resistive and compliance states. RESULTS:
      The VN500, but not the SM3100, demonstrated an exponential decrease in airway
      opening DeltaP as frequency increased. The difference between the SM3100- and
      VN500-delivered VTHF became greater with each frequency increment. At 15 Hz,
      VN500 VTHF was 49% of SM3100 VTHF . CONCLUSIONS: The VN500 demonstrates a
      frequency-related reduction in DeltaP not observed in the SM3100. Clinicians need
      to be aware of these differences in performance characteristics.

PMID- 24118668
TI  - Unlocking the vault: next-generation museum population genomics.
AB  - Natural history museum collections provide unique resources for understanding how
      species respond to environmental change, including the abrupt, anthropogenic
      climate change of the past century. Ideally, researchers would conduct genome
      scale screening of museum specimens to explore the evolutionary consequences of
      environmental changes, but to date such analyses have been severely limited by
      the numerous challenges of working with the highly degraded DNA typical of
      historic samples. Here, we circumvent these challenges by using custom,
      multiplexed, exon capture to enrich and sequence ~11,000 exons (~4 Mb) from early
      20th-century museum skins. We used this approach to test for changes in genomic
      diversity accompanying a climate-related range retraction in the alpine chipmunks
      (Tamias alpinus) in the high Sierra Nevada area of California, USA. We developed
      robust bioinformatic pipelines that rigorously detect and filter out base
      misincorporations in DNA derived from skins, most of which likely resulted from
      postmortem damage. Furthermore, to accommodate genotyping uncertainties
      associated with low-medium coverage data, we applied a recently developed
      probabilistic method to call single-nucleotide polymorphisms and estimate allele
      frequencies and the joint site frequency spectrum. Our results show increased
      genetic subdivision following range retraction, but no change in overall genetic
      diversity at either nonsynonymous or synonymous sites. This case study showcases
      the advantages of integrating emerging genomic and statistical tools in museum
      collection-based population genomic applications. Such technical advances greatly
      enhance the value of museum collections, even where a pre-existing reference is
      lacking and points to a broad range of potential applications in evolutionary and
      conservation biology.

PMID- 24118672
TI  - Long-term effect of salinity on plant quality, water relations, photosynthetic
      parameters and ion distribution in Callistemon citrinus.
AB  - The effect of saline stress on physiological and morphological parameters in
      Callistemon citrinus plants was studied to evaluate their adaptability to
      irrigation with saline water. C. citrinus plants, grown under greenhouse
      conditions, were subjected to two irrigation treatments lasting 56 weeks: control
      (0.8 dS.m(-1)) and saline (4 dS.m(-1)). The use of saline water in C. citrinus
      plants decreased aerial growth, increased the root/shoot ratio and improved the
      root system (increased root diameter and root density), but flowering and leaf
      colour were not affected. Salinity caused a decrease in stomatal conductance and
      evapotranspiration, which may prevent toxic levels being reached in the shoot.
      Net photosynthesis was reduced in plants subjected to salinity, although this
      response was evident much later than the decrease in stomatal conductance. Stem
      water potential was a good indicator of salt stress in C. citrinus. The relative
      salt tolerance of Callistemon was related to storage of higher levels of Na+ and
      Cl- in the roots compared with the leaves, especially in the case of Na+, which
      could have helped to maintain the quality of plants. The results show that saline
      water (around 4 dS.m(-1)) could be used for growing C. citrinus commercially.
      However, the cumulative effect of irrigating with saline water for 11 months was
      a decrease in photosynthesis and intrinsic water use efficiency, meaning that the
      interaction of the salinity level and the time of exposure to the salt stress
      should be considered important in this species.

PMID- 24118671
TI  - Lomitapide at supratherapeutic plasma levels does not prolong the Qtc interval-
      results from a TQT study with moxifloxacin and ketoconazole.
AB  - BACKGROUND: The aim of this study was to assess the effect of high plasma levels
      of lomitapide and its main metabolite on ECG parameters. METHODS: In this
      randomized five-way cross-over thorough QT study, 56 healthy subjects were
      enrolled. Study treatments were administered orally for 3 days in five separate
      periods in which subjects were dosed with (1) a single dose of 75 mg lomitapide
      on Day 1 followed by a single dose of 200 mg on Day 3; (2) ketoconazole 200 mg
      BID; (3) ketoconazole with a single dose of 75 mg lomitapide on Day 3; (4) a
      single dose of 400 mg moxifloxacin on Day 3 and (5) placebo. RESULTS: Single
      doses of 75 and 200 mg lomitapide alone or in combination with ketoconazole
      caused minor changes in the change-from-baseline QTcI (DeltaQTcI), whereas
      moxifloxacin and ketoconazole caused an increase of DeltaQTcI with a peak effect
      at 1 and 3 hours postdosing, respectively. The largest mean placebo-corrected
      DeltaQTcI (DeltaDeltaQTcI) for lomitapide did not exceed 3 ms (upper bound of 90%
      CI: 4.7 ms) at any time points postdosing. Ketoconazole caused mild QT
      prolongation with mean DeltaDeltaQTcI of 5.9 and 6.5 ms at 2 and 3 hours
      postdosing, and exposure-response analysis demonstrated a significantly positive
      slope of 1.3 ms per MUg/mL (90% CI: 1.0-1.7). Moxifloxacin met the criteria for
      assay sensitivity. CONCLUSIONS: Lomitapide does not have an effect on cardiac
      repolarization. The study's ability to detect small QTc changes was demonstrated
      with both moxifloxacin and ketoconazole.

PMID- 24118673
TI  - Hybrid transanal endoscopic microsurgery: a novel approach to rectal neoplasm
      excision.
AB  - AIM: Rectal neoplasm excision is a challenging issue in gastrointestinal
      endoscopy and surgery. This technical note describes a hybrid method for the
      excision of challenging rectal neoplasms. METHOD: The procedure consists of the
      combined use of classic endoscopy and transanal endoscopic microsurgical
      instrumentation for full-thickness removal of a recurrent rectal polyp in a
      patient who had previously undergone endoscopic excision of a Tis rectal
      adenocarcinoma, located behind the valve of Houston and 9 cm from the anal verge.
      RESULTS: The lesion was removed completely in 50 min with no operative
      complication. The patient's postoperative course was uneventful, and she was
      discharged after 5 days. Pathological examination of the specimen confirmed
      complete resection of the lesion with adequate disease-free margins. CONCLUSION:
      Hybrid transanal endoscopic microsurgery successfully combines the precision and
      flexibility of classic endoscopy with the radicality and safety of transanal
      endoscopic microsurgery for the treatment of demanding benign or early-stage
      malignant rectal tumours.

PMID- 24118674
TI  - Use of periurethral injections of polyacrylamide hydrogel for treating post
      vesicovaginal fistula closure urinary stress incontinence.
AB  - AIMS: Following successful closure of obstetric genitourinary fistula, stress
      urinary incontinence (SUI) is a common and challenging problem. Despite many
      decades of various treatment options, the effective management of post-fistula
      SUI remains unresolved. This study aims to assess the feasibility of periurethral
      injections of polyacrylamide hydrogel, commonly used for urinary stress
      incontinence in non-fistula women, in women with post-fistula closure SUI.
      MATERIAL AND METHODS: Women with urinary incontinence following successful
      fistula closure were assessed to exclude detrusor overactivity and urinary
      residual volumes of more than 100 mL. The urethrovesical junction was identified
      and polyacrylamide hydrogel was injected through the periurethral skin and
      vaginal epithelium at three sites. RESULTS: Four women with post-fistula SUI were
      treated with polyacrylamide hydrogel injections. Three of the four women were dry
      post-operatively and remained continent at discharge. CONCLUSION: In the short
      term, periurethral injections of polyacrylamide hydrogel appears to be a
      promising method to treat post-obstetric fistula urinary stress incontinence.

PMID- 24118675
TI  - Influence of activation mode of resin cement on the shade of porcelain veneers.
AB  - PURPOSE: The aim of this study was to evaluate the influence of resin luting
      cement's activation mode in the final shade of porcelain veneers after
      accelerated artificial aging (AAA). MATERIALS AND METHODS: Porcelain veneers (IPS
      Empress Esthetic) were produced using a standardized shade (ET1) and thickness
      (0.6 mm). Twenty bovine teeth were collected, prepared, and divided into two
      groups: group I (n = 10)-light-cured group, only base paste was applied to the
      veneers; group II (n = 10)-dual-cured group, in which the same base paste used in
      group I and a transparent catalyst were proportionally mixed for 20 seconds and
      then applied to the veneers. The specimens were light-cured for 60 seconds each
      and were next subjected to AAA. They were submitted to color readings with a
      spectrophotometer in three instances: in the tooth surface (only the substrate),
      after the cementation and polymerization of the veneers, and after the AAA. The
      values of L*, a*, and b* were obtained and the total color change was calculated
      (?E*). Values obtained were subjected to statistical analysis, with a
      significance of 0.05. RESULTS: There were no significant differences between dual
      and light-cured modes considering ?E*, L*, a*, and b* values obtained after
      aging (p > 0.05). Within the dual-cured mode there were no significant
      differences in ?E*, L*, a*, and b* values (p > 0.05). CONCLUSION: No relevant
      differences were found between the two activation modes in color change. When
      submitted to aging, dual- and light-cured modes of the resin cement showed
      visually perceptible (?E* > 1.0) color changes; however, within the threshold of
      clinical acceptance (?E* > 3.3).

PMID- 24118676
TI  - Understanding the causation of primary angle closure disease using the sufficient
      component cause model.
AB  - BACKGROUND: Several risk factors have been associated with primary angle closure
      disease, but their actual role in causation of an individual case is not clear.
      DESIGN: Concept paper. PARTICIPANTS/SAMPLES: No patient participation. METHODS:
      The sufficient component cause model is briefly explained in the context of
      primary angle closure disease. The framework is used to conceptualize the role of
      individual mechanisms of disease. The possibility of personalized treatment for
      primary angle closure disease is discussed in this context. MAIN OUTCOME
      MEASURES: Qualitative concepts in disease causality may refine research and
      treatment in primary angle closure disease. RESULTS: The minimum set of
      conditions that are sufficient for primary angle closure disease to occur is
      considered the sufficient component cause model for that individual case.
      Described risk factors (including genes) as well as currently unknown influences
      play a role in the model. There may be many such models and all complementary
      components in any sufficient-cause model must be present for disease to occur.
      Interruption of any one component in that model can be used for treatment.
      Pupillary block is likely a component of most such models and may currently be
      considered a universally necessary component of these models. CONCLUSIONS: The
      sufficient component cause model can be used as a framework to explain the role
      of individual mechanisms of causation and treatment of primary angle closure
      disease. It also aids understanding of the proportion of disease due to specific
      causes.

PMID- 24118677
TI  - Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant
      treatment of canine appendicular osteosarcoma: a randomized, phase III trial.
AB  - Despite numerous published studies describing adjuvant chemotherapy for canine
      appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy
      protocol. The purpose of this study was to determine whether either of two
      protocols would be associated with longer disease-free interval (DFI) in dogs
      with appendicular osteosarcoma following amputation. Dogs with histologically
      confirmed appendicular osteosarcoma that were free of gross metastases and
      underwent amputation were eligible for enrollment. Dogs were randomized to
      receive either six doses of carboplatin or three doses each of carboplatin and
      doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving
      carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs
      receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was
      similar between groups. These results suggest that six doses of carboplatin may
      be associated superior DFI when compared to six total doses of carboplatin and
      doxorubicin. 

PMID- 24118678
TI  - The relative contribution of drift and selection to transcriptional divergence
      among Babine Lake tributary populations of juvenile rainbow trout.
AB  - Fine-scale population structure has been widely described for salmonid
      populations using neutral genetic markers, but whether that structure reflects
      adaptive differences among the populations remains of interest to evolutionary
      biologists and conservation managers alike. The use of transcriptomics to
      quantify population differences in genetically controlled functional gene
      expression traits holds promise for investigating this divergence associated with
      possible local adaptation. We use custom microarrays to characterize population
      divergence in transcription at functionally relevant (metabolic and immune
      function) genes among tributary populations of rainbow trout from Babine Lake, BC
      and compare it to neutral divergence estimated from microsatellite markers.
      Transcriptional divergence (PST ) was determined at resting state and in response
      to metabolic and immune challenges, two major sources of mortality and thus
      selective forces on juvenile salmonids. Results indicate that the majority of
      selected genes [56 genes (65%), 64 genes (63%) and 38 genes (78%) under control,
      temperature and immune challenges respectively] show transcriptional divergence
      (PST  > FST ) that is consistent with the action of divergent selection. Patterns
      of pairwise PST among populations are inconsistent with evolution by drift. In
      general, it appears that the magnitude and pattern of population divergence in
      transcription reflect the action of natural selection and identify selection on
      transcription as a mechanism for local adaptation. These results reinforce the
      need to conserve salmonids on a tributary basis and provide insight into genetic
      mechanisms that facilitate local adaptation. 

PMID- 24118679
TI  - Propagation of MinCDE waves on free-standing membranes.
AB  - As a spatial modulator of cytokinesis in Escherichia coli, the Min system
      cooperates with the nucleoid occlusion mechanism to target the divisome assembly
      towards mid-cell. Based on a reaction-diffusion mechanism powered by ATP
      (adenosine triphosphate) hydrolysis, the Min proteins propagate in waves on the
      cell membrane, resulting in oscillations between the cell poles, thus preventing
      the formation of the division ring everywhere but in the cell centre. The dynamic
      behaviour of Min proteins has been successfully reconstructed in vitro on
      supported lipid bilayers (SLBs), reproducing many of the features observed in the
      cell. However, there has been a marked discrepancy between the speed of
      propagation of Min protein waves in vitro, compared with the cellular system. A
      very plausible explanation is the different mobility of proteins on model
      membranes, compared with the inner membrane of bacteria. To quantitatively
      demonstrate how membrane diffusion influences Min wave propagation, we compared
      Min waves on SLBs with free-standing giant unilamellar vesicles (GUV) membranes
      which display higher fluidity. Intriguingly, the propagation velocity and
      wavelength on GUVs are three times higher than those reported on supported
      bilayers, but the wave period is conserved. This suggests that the shorter
      spatial period of the patterns in vivo might indeed be primarily explained by
      lower diffusion coefficients of proteins on the bacterial inner membrane. 

PMID- 24118680
TI  - How much time do nurses need to write an ICU diary?
AB  - BACKGROUND: Diaries in the Intensive Care Unit (ICU) support patients and
      relatives during and after a stay on the ICU. Barriers to implementation of the
      ICU diary are workload, unwanted closeness to patients and lack of time. AIMS AND
      OBJECTIVES: The purpose of the study was to evaluate the time nurses consume
      writing an ICU diary. Further questions were to examine whether the first diary
      entry, which includes a more detailed description about the admission, consumes
      more time than other entries and whether the time taken depends on experience or
      workload of the nurses. DESIGN: Quantitative, prospective, international
      observational multicentre study in four ICUs within the international diary
      network in Germany (two ICUs), Sweden and Switzerland (one ICU each). METHOD:
      During a 6-month period in 2012/2013 nurses measured the time they consumed
      writing a diary in minutes and seconds, the number of diaries they contributed to
      and total number of diary entries, the nurse-patient ratio, their level of
      experience in writing diaries, interruptions while writing in a diary and
      additional information like photographs or follow-up visits. RESULTS: In summary
      29 diaries were collected which included 195 written entries. The first entry
      needed significantly more time than following entries (first entry: mean 13:33
      min versus following entries: mean 5:31, p < 0.001). The mean time for following
      entries differed significantly between the countries: Switzerland: 6:14, Sweden
      5:31 and Germany 3:36 (p < 0.001). Nurses with more experience used more time to
      write a diary (not significant). With increasing nurse-patient-ratio the time
      decreased for following entries (ratio 1:1: mean 5:42, ratio 1:2: mean 5:27,
      ratio 1:3: mean 3:12, p = 0.007). CONCLUSION: Writing a diary for patients and
      relatives means an additional amount of time and workload, but according to the
      increased quality of nursing the time seems to be feasible for implementation.
      The measured time was self-reported, thus including possible bias for the
      results.

PMID- 24118681
TI  - DnaT is a single-stranded DNA binding protein.
AB  - DnaT is one of the replication restart primosomal proteins required for
      reinitiating chromosomal DNA replication in bacteria. In this study, we
      identified and characterized the single-stranded DNA (ssDNA)-binding properties
      of DnaT using electrophoretic mobility shift analysis (EMSA), bioinformatic tools
      and two deletion mutant proteins, namely, DnaT26-179 and DnaT42-179. ConSurf
      analysis indicated that the N-terminal region of DnaT is highly variable. The
      analysis of purified DnaT and the deletion mutant protein DnaT42-179 by gel
      filtration chromatography showed a stable trimer in solution, indicating that the
      N-terminal region, amino acid 1-41, is not crucial for the oligomerization of
      DnaT. Contrary to PriB, which forms a single complex with a series of ssDNA
      homopolymers, DnaT, DnaT26-179 and DnaT42-179 form distinct complexes with ssDNA
      of different lengths and the size of binding site of 26 +/- 2 nucleotides (nt).
      Using bioinformatic programs (ps)(2) and the analysis of the positively
      charged/hydrophobic residue distribution, as well as the biophysical results in
      this study, we propose a binding model for the DnaT trimer-ssDNA complex, in
      which 25-nt-long ssDNA is tethered on the surface groove located in the highly
      conserved C-terminal domain of DnaT. These results constitute the first study
      regarding ssDNA-binding activity of DnaT. Consequently, a hand-off mechanism for
      primosome assembly was modified. 

PMID- 24118682
TI  - An introduction to clinical practice guideline for Chinese undergraduates in
      stomatology.
AB  - The Society of Dental Education, Chinese Stomatological Association has
      formulated the Standards of Clinical Practice for Chinese Undergraduate Students
      Majoring in Stomatology, on the basis of extensively soliciting the views of
      experts in various fields. The aim of this standard is to guide clinical teaching
      and improve teaching quality in schools of stomatology in China. The standards
      include eight parts: the standard of clinical practice for oral and maxillofacial
      surgery, for cariology and endodontics, for periodontics, for the oral mucosa
      diseases, for preventive dentistry, for pedodontology, for prosthodontics and for
      oral imageology. Each part includes introduction to subjects, the clinical
      practice time period, the purpose and requirements of practice, the disease types
      of practice and items of clinical operation, the index of the lowest workload of
      practice and the major methods of assessment. These standards are not only the
      basic requirements and guiding principles for clinical teaching, but also the
      major criteria for assessing the clinical teaching quality of stomatological
      colleges/schools of China. 

PMID- 24118683
TI  - A combination of interferon-gamma and interleukin-2 production by Coxiella
      burnetii-stimulated circulating cells discriminates between chronic Q fever and
      past Q fever.
AB  - Infection with Coxiella burnetii may lead to life-threatening chronic Q fever
      endocarditis or vascular infections, which are often difficult to diagnose. The
      present study aims to investigate whether measurement of in-vitro interferon
      gamma (IFN-gamma) production, a key cytokine in the immune response against C.
      burnetii, differentiates chronic from a past cleared infection, and whether
      measurement of other cytokines would improve the discriminative power. First, C.
      burnetii-specific IFN-gamma production was measured in whole blood of 28 definite
      chronic Q fever patients and compared with 135 individuals with past Q fever
      (seropositive controls) and 908 seronegative controls. IFN-gamma production was
      significantly higher in chronic Q fever patients than in controls, but with
      overlapping values between patients and seropositives. Secondly, the production
      of a series of other cytokines was measured in a subset of patients and controls,
      which showed that interleukin (IL)-2 production was significantly lower in
      patients than in seropositive controls. Subsequently, measuring IL-2 in all
      patients and all controls with substantial IFN-gamma production showed that an
      IFN-gamma/IL-2 ratio >11 had a sensitivity and specificity of 79% and 96%,
      respectively, to diagnose chronic Q fever. This indicates that a high IFN
      gamma/IL-2 ratio is highly suggestive for chronic Q fever. In an additional group
      of 25 individuals with persistent high anti-Coxiella phase I IgG titres without
      definite chronic infection, all but six showed an IFN-gamma/IL-2 ratio <11. In
      conclusion, these findings hold promise for the often difficult diagnostic work
      up of Q fever and the IFN-gamma/IL-2 ratio may be used as an additional
      diagnostic marker.

PMID- 24118684
TI  - Quality of life, social support, and severity of psychiatric symptoms in
      Jordanian patients with schizophrenia.
AB  - The major purposes of this study were to examine levels and correlations of
      quality of life (QOL), social support, and severity of psychiatric symptoms as
      well as to identify the variables that best predict QOL among Jordanian patients
      with schizophrenia. Descriptive cross-sectional design was used to collect data
      from 160 patients selected through systematic random sampling from two
      psychiatric outpatient clinics. Results showed that the highest domain of QOL was
      the social relationship domain, and the highest source of social support was
      perceived from significant others. Severity of affective symptoms was the
      highest, and severity of positive symptoms was the lowest. QOL correlated
      positively with social support, patients' educational and income level, and
      employment; and negatively with severity of psychiatric symptoms, duration of
      untreated illness, and duration of treatment. Support from friends, duration of
      untreated illness, income level, and severity of affective symptoms predicted QOL
      and accounting for 47.3% of the variance.

PMID- 24118686
TI  - Hymenoscyphus pseudoalbidus, the causal agent of European ash dieback.
AB  - The ascomycete Hymenoscyphus pseudoalbidus (anamorph Chalara fraxinea) causes a
      lethal disease known as ash dieback on Fraxinus excelsior and Fraxinus
      angustifolia in Europe. The pathogen was probably introduced from East Asia and
      the disease emerged in Poland in the early 1990s; the subsequent epidemic is
      spreading to the entire native distribution range of the host trees. This
      pathogen profile represents a comprehensive review of the state of research from
      the discovery of the pathogen and points out knowledge gaps and research needs.
      TAXONOMY: Members of the genus Hymenoscyphus (Helotiales, Leotiomycetidae,
      Leotiomycetes, Ascomycota) are small discomycetes which form their ascomata on
      dead plant material. A phylogeny based on the internal transcribed spacers (ITSs)
      of the rDNA indicated the avirulent Hymenoscyphus albidus, a species native to
      Europe, as the closest relative of H. pseudoalbidus. SYMPTOMS: Hymenoscyphus
      pseudoalbidus causes necrotic lesions on leaves, twigs and stems, eventually
      leading to wilting and dieback of girdled shoots. Bark lesions are characterized
      by a typical dark- to cinnamon-brown discoloration. LIFE CYCLE: Hymenoscyphus
      pseudoalbidus is heterothallic and reproduces sexually on ash petioles in the
      litter once a year. Ascospores are wind dispersed and infect ash leaves during
      the summer. The asexual spores only serve as spermatia. TOOLS AND TECHNIQUES: The
      most important techniques for fungal handling, such as detection, isolation,
      culturing, storage, crossing and ascocarp production, are briefly described.
      MANAGEMENT: Once the disease is established, management is hardly possible. The
      occurrence of a small fraction of partially tolerant trees constitutes hope for
      resistance breeding in the future. Healthy-looking trees should be preserved.

PMID- 24118687
TI  - Sixty plus years of reflections on the medical profession by an "old-timer".

PMID- 24118689
TI  - Role of depressive symptoms and self-efficacy of medication adherence in Korean
      patients after successful percutaneous coronary intervention.
AB  - This cross-sectional study sought to identify the prevalence of medication
      adherence and to explore the role of depression and self-efficacy on medication
      adherence among patients with coronary artery diseases. Participants were
      recruited among outpatients who successfully underwent primary percutaneous
      coronary intervention (PCI) with drug-eluting stent at academic medical centres
      in Cheonan, South Korea. Medication adherence was evaluated by the eight-item
      Morisky Medication Adherence Scale using a validated Korean version. Prevalence
      of non-adherent to medication was 60.3%. With non-depressed and high self
      efficacy as reference and after adjusting for age and gender, the models showed
      that those with depression and low self-efficacy are more likely to be non
      adherent to medication. Therefore, future studies should focus on the development
      of interventions designed to reduce depression and increase self-efficacy for
      improving patient adherence to cardiovascular medications following PCI. 

PMID- 24118688
TI  - Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus
      inadequately controlled with metformin and sulphonylurea: a randomised trial.
AB  - AIMS: Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for
      the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind,
      placebo-controlled, Phase 3 study evaluated the efficacy and safety of
      canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM.
      METHODS: Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once
      daily during a 26-week core period and a 26-week extension. Prespecified primary
      end-point was change in HbA1c at 26 weeks. Secondary end-points included change
      in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0%,
      change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent
      change in body weight, high-density lipoprotein cholesterol, and triglycerides
      (weeks 26 and 52). RESULTS: HbA1c was significantly reduced with canagliflozin
      100 and 300 mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p < 0.001);
      these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both
      canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p <
      0.001) and week 52. Overall adverse event (AE) rates were similar across groups
      over 52 weeks, with higher rates of genital mycotic infections and osmotic
      diuresis-related AEs seen with canagliflozin vs. placebo; these led to few
      discontinuations. Increased incidence of documented, but not severe,
      hypoglycaemia episodes was seen with canagliflozin vs. placebo. CONCLUSIONS:
      Canagliflozin improved glycaemic control, reduced body weight, and was generally
      well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks.

PMID- 24118690
TI  - Are we missing a simple treatment for most adult sleep apnea patients? The
      avoidance of the supine sleep position.
AB  - Obstructive sleep apnea (OSA) is a sleep disorder which has been gradually
      accepted as an important cause of increased morbidity and mortality. The
      treatment of moderate-severe OSA has improved dramatically since the introduction
      of continuous positive airway pressure (CPAP) devices; however, the adherence of
      patients to CPAP treatment is relatively low. Adherence appears to be even worse
      in patients with mild or asymptomatic OSA. The failure to identify and treat
      mildly symptomatic or asymptomatic OSA patients may be costly, as such patients
      comprise about 20% of the general adult population. OSA patients could be divided
      into positional and non-positional patients. Positional patients show most of
      their breathing abnormalities while sleeping in the supine position. Simply, by
      sleeping in the lateral postures, they eliminate or reduce significantly the
      number of apneas and hypopneas. On the contrary, non-positional patients suffer
      from breathing abnormalities in the supine and lateral postures, and as a
      consequence those are the most severe OSA patients for whom CPAP is the treatment
      of choice. In this paper we intend to argue that positional therapy, i.e.,
      avoidance of the supine posture during sleep, could represent a valuable therapy
      mainly for mild-moderate OSA. Considering the fact that the vast majority of mild
      moderate OSA patients are positional patients (between 65 and 87%), positional
      therapy may be a simple, cheap and effective solution for them. High-quality
      research regarding this issue is needed to evaluate the real effectiveness of
      this mode of therapy.

PMID- 24118691
TI  - A new theoretical model for the development of pressure ulcers and other
      dependence-related lesions.
AB  - OBJECTIVE: To review the risk factors included in pressure ulcer risk assessment
      scales and construct a theoretical model for identifying the etiological factors
      of skin ulcers, excluding those of systemic origin (e.g., venous, arterial, and
      neuropathic). METHODS: Consensus study with expert panel (Delphi Method) based on
      a structured review of the literature. A search was conducted of the main
      databases between 1962 and 2009 with no language limitations. All descriptive or
      validation studies were included, but the grey literature was excluded. After
      identifying the risk factors in each scale, they were grouped into risk
      dimensions as a basis for constructing a new theoretical model. RESULTS: Eighty
      three risk factors were identified in the 56 scales reviewed, and the risk
      factors were then classified by the expert panel into 23 risk dimensions. These
      dimensions were used to construct a new theoretical model (middle-range theory)
      for chronic wound development that explains the production mechanism of seven
      types of lesion: moisture, pressure, friction, combined pressure-moisture,
      combined pressure-friction, multifactorial lesions, and coadjuvant factors. These
      lesions were generically defined as dependence-related injuries. CONCLUSIONS:
      Based on the classification of risk factors from the different scales into risk
      dimensions, a new middle-range theory was constructed that explains the
      production mechanism of seven dependence-related lesions considered to date as
      pressure ulcers. CLINICAL RELEVANCE: The prevention and treatment of these
      lesions requires a correct diagnosis and differentiation of their cause and
      management of the risk dimensions involved. The type of lesion also influences
      the selection of local approach.

PMID- 24118692
TI  - Cancer research by means of tissue engineering--is there a rationale?
AB  - Tissue engineering (TE) has evoked new hopes for the cure of organ failure and
      tissue loss by creating functional substitutes in the laboratory. Besides various
      innovations in the context of Regenerative Medicine (RM), TE also provided new
      technology platforms to study mechanisms of angiogenesis and tumour cell growth
      as well as potentially tumour cell spreading in cancer research. Recent advances
      in stem cell technology--including embryonic and adult stem cells and induced
      pluripotent stem cells--clearly show the need to better understand all relevant
      mechanisms to control cell growth when such techniques will be administered to
      patients. Such TE-Cancer research models allow us to investigate the interactions
      that occur when replicating physiological and pathological conditions during the
      initial phases of replication, morphogenesis, differentiation and growth under
      variable given conditions. Tissue microenvironment has been extensively studied
      in many areas of TE and it plays a crucial role in cell signalling and regulation
      of normal and malignant cell functions. This article is intended to give an
      overview on some of the most recent developments and possible applications of TE
      and RM methods with regard to the improvement of cancer research with TE
      platforms. The synthesis of TE with innovative methods of molecular biology and
      stem-cell technology may help investigate and potentially modulate principal
      phenomena of tumour growth and spreading, as well as tumour-related angiogenesis.
      In the future, these models have the potential to investigate the optimal
      materials, culture conditions and material structure to propagate tumour growth.

PMID- 24118694
TI  - Perineal body repair in patients with third degree rectocele: a critical analysis
      of the tissue fixation system.
AB  - AIM: We describe the technique of tissue fixation system (TFS) perineal body
      repair in patients presenting with symptomatic third degree rectocele. METHOD:
      The single sling TFS perineal body repair is performed in three surgical steps:
      (i) dissection of the rectum off the vagina and laterally displaced perineal
      body; (ii) identification of the deep transverse perineii muscles beyond their
      insertion point behind the descending pubic ramus; (iii) elevation and
      approximation of the separated and laterally displaced perineal bodies by
      insertion, without tension, of non-stretch 7 mm polypropylene tape into the
      bodies of the deep transverse perineii muscles. RESULTS: From January 2007 to
      December 2009 we performed the TFS operation for 30 women, median age 61 (range
      47-87) years, mean parity 2.6 (range 1-5), with third degree symptomatic low
      rectocele (median obstructive defaecation syndrome score 19; range 11-24). Median
      hospital stay was 24 (range 12-96) h. The median visual analogue scale for
      postoperative pain was 1 (range 1-7). Complications occurred in three cases (10%)
      and included a surfaced tape that was partly resected (repair maintained), a
      recurrence of the rectocele due to incorrect placement (failed repair) and a
      foreign body abscess requiring tape removal. At 12-month follow-up, 27 patients
      (90%) reported normal defaecation and the median obstructive defaecation syndrome
      score was significantly reduced to 4 (range 1-6; P < 0.001). CONCLUSION: The TFS
      perineal body repair is an effective, safe, minimally invasive treatment in women
      with symptomatic low rectocele.

PMID- 24118693
TI  - Diabetes mellitus and advanced liver fibrosis are risk factors for severe anaemia
      during telaprevir-based triple therapy.
AB  - BACKGROUND & AIMS: Adding telaprevir to pegylated-interferon and ribavirin
      increased both response rates and side effects of hepatitis C virus (HCV)
      treatment. We identified variables associated with severe anaemia during
      telaprevir-based triple therapy. METHODS: An observational study was performed on
      142 HCV-infected patients between June 2011 and March 2012. All subjects
      completed 12 weeks of telaprevir-based triple therapy or discontinued early
      because of anaemia. Severe anaemia was defined by a haemoglobin<=8.9 g/dl;
      advanced fibrosis was determined by Fib-4>=3.25. RESULTS: The 47 (33%) patients
      who developed severe anaemia were similar to those who did not in sex, race, and
      prior response to dual therapy, but they were more likely to have diabetes (23.4%
      vs. 6.3%, P<0.01), advanced fibrosis (46.8% vs. 29.5%, P=0.04) and a history of
      anaemia during previous dual therapy (29.7% vs. 11.4%, P=0.02). Patients
      developing severe anaemia were older (59 vs. 56 years, P=0.02), had lower
      baseline platelet counts (134 vs. 163*10(9) /L, P=0.04), haemoglobin (14.0 vs.
      15.0 g/dl, P<0.01), estimated glomerular filtration rate (79 vs. 90 ml/min/1.73
      m2, P=0.03) and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg,
      P<0.01). In multivariable logistic regression, presence of diabetes (OR=5.61, 95%
      CI: 1.59-19.72), Fib-4>=3.25 (OR=3.09, 95% CI: 1.28-7.46), higher
      ribavirin/weight ratio (OR=1.31 per mg/kg, 95% CI: 1.13-1.52) and lower baseline
      haemoglobin (OR=0.57 per g/dl, 95% CI, 0.41-0.80) were independently associated
      with developing severe anaemia. CONCLUSIONS: Severe anaemia occurred in one-third
      of patients receiving telaprevir-based triple therapy. Risk was greater in
      patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio
      and lower baseline haemoglobin.

PMID- 24118695
TI  - Angiosome-targeted revascularisation in diabetic foot ulcers.
AB  - Peripheral vascular disease is a common complication of type 2 diabetes and is
      often more severe and diffuse than in non-diabetic individuals with a higher risk
      of major amputations in the lower limbs. Diabetic foot revascularisation using
      both traditional bypass surgery and endovascular therapy are often burdened by
      the failure and the inevitable subsequent massive amputation. In this study, we
      examined the clinical response of diabetic patients with critical limb ischaemia
      and extended ischaemic wounds, treated with a new angiosome-based
      revascularisation technique. In a 3-year period, nine diabetic patients with
      imminent amputation threatening and foot ulcers with no feasible arterial
      revascularisation options were treated by the angiosome-based surgical technique
      by means of deep vein arterialisation. The postoperative tcPO2 evaluation showed
      a mean increase in the cutaneous oxygen tension in all patients treated. The
      overall survival rates were 88.88%, 88.88% and 77.77% at 12, 24 and 36 months,
      respectively. Limb salvage was 100% at 1 year and steady at 88.88% thereafter.
      Surgical deep venous arterialisation might be considered as an extreme
      alternative to attempt tissue preservation in limbs unfit for conventional
      arterial revascularisations. This technique would give advantages to the patients
      in terms of better compliance to the minor amputations and thus avoiding major
      limb amputations. 

PMID- 24118696
TI  - Melatonin and female reproduction.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at
      night by the pineal gland. After entering the circulation, melatonin acts as an
      endocrine factor and a chemical messenger of light and darkness. It regulates a
      variety of important central and peripheral actions related to circadian rhythms
      and reproduction. It also affects the brain, immune, gastrointestinal,
      cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and
      anti-aging molecule. Many of melatonin's actions are mediated through
      interactions with specific membrane-bound receptors expressed not only in the
      central nervous system, but also in peripheral tissues. Melatonin also acts
      through non-receptor-mediated mechanisms, for example serving as a scavenger for
      reactive oxygen species and reactive nitrogen species. At both physiological and
      pharmacological concentrations, melatonin attenuates and counteracts oxidative
      stress and regulates cellular metabolism. Growing scientific evidence of
      reproductive physiology supports the role of melatonin in human reproduction.
      This review was conducted to investigate the effects of melatonin on female
      reproduction and to summarize our findings in this field. 

PMID- 24118697
TI  - Reporting standards in experimental studies.

PMID- 24118698
TI  - Remodelling of retinal on- and off-bipolar cells following experimental retinal
      detachment.
AB  - BACKGROUND: To study the response of ON and OFF bipolar cells in experimental
      retinal detachment. METHODS: Domestic cat retinas were detached for 7 days. The
      retinas were prepared for immunocytochemical staining with antibodies to Go alpha
      (alpha), glutamate transporter GLT-1, protein kinase C and rod opsin, which serve
      as markers for ON bipolar cells, OFF bipolar cells, rod bipolar cells and rod
      photoreceptors, respectively. Both sections and whole-mounts were labelled with
      antibodies to Goalpha and GLT-1. RESULTS: Following 7 days of detachment, ON
      bipolar cell processes extended into the outer nuclear layer and had neurites
      extending beyond their target layer into the inner plexiform layer. In contrast,
      OFF bipolar cell processes were reduced in the outer plexiform layer following
      detachment. CONCLUSION: ON and OFF bipolar cells undergo significant remodelling
      of their processes in response to retinal detachment, and the ON and OFF pathways
      may be differentially affected. The remodelling may be due to morphological
      changes that have previously been shown to occur in photoreceptor synaptic
      terminals or as a result of loss of synaptic connections due to photoreceptor
      cell death.

PMID- 24118699
TI  - Soil water flow is a source of the plant pathogen Pseudomonas syringae in
      subalpine headwaters.
AB  - The airborne plant pathogenic bacterium Pseudomonas syringae is ubiquitous in
      headwaters, snowpack and precipitation where its populations are genetically and
      phenotypically diverse. Here, we assessed its population dynamics during snowmelt
      in headwaters of the French Alps. We revealed a continuous and significant
      transport of P.syringae by these waters in which the population density is
      correlated with water chemistry. Via in situ observations and laboratory
      experiments, we validated that P.syringae is effectively transported with the
      snow melt and rain water infiltrating through the soil of subalpine grasslands,
      leading to the same range of concentrations as measured in headwaters (10(2) 
      10(5) CFU l(-1) ). A population structure analysis confirmed the relatedness
      between populations in percolated water and those above the ground (i.e. rain,
      leaf litter and snowpack). However, the transport study in porous media suggested
      that water percolation could have different efficiencies for different strains of
      P.syringae. Finally, leaching of soil cores incubated for up to 4 months at 8
      degrees C showed that indigenous populations of P.syringae were able to survive
      in subalpine soil under cold temperature. This study brings to light the
      underestimated role of hydrological processes involved in the long distance
      dissemination of P.syringae.

PMID- 24118701
TI  - Does obesity affect knee cartilage? A systematic review of magnetic resonance
      imaging data.
AB  - There is increasing evidence for the effect of obesity on knee osteoarthritis
      (OA), although the association between obesity, particularly body composition,
      and knee osteoarthritis, using magnetic resonance imaging (MRI) to examine knee
      structure, has not been examined. We systematically evaluated the evidence for
      the relationship between obesity and knee cartilage assessed by MRI. We performed
      an electronic search of MEDLINE and EMBASE up to December 2012. Included studies
      investigated the association between obesity and the development and/or
      progression of knee cartilage changes using MRI. The studies were ranked
      according to their methodological score and best-evidence synthesis was performed
      to summarize the results Twenty-two studies were identified for inclusion, of
      which 7 were cross-sectional, 13 were longitudinal and 2 had both cross-sectional
      and longitudinal components. Seven cross-sectional and eight longitudinal studies
      were of high quality. Best-evidence synthesis showed consistent, yet limited
      evidence for a detrimental effect of body mass index (BMI) and fat mass on knee
      cartilage. This review identified a consistent detrimental effect of obesity,
      particularly related to elevated BMI and fat mass on cartilage defects. The
      strength of evidence was limited by the paucity of high-quality cohort studies
      examining this question. By further examining the mechanisms for these different
      effects, new strategies can be developed to prevent and treat knee OA. 

PMID- 24118700
TI  - The effect of intraspinal bupivacaine versus levobupivacaine on the QTc intervals
      during caesarean section: a randomized, double-blind, prospective study.
AB  - The aim of this study was to describe whether or not spinal anaesthesia with
      bupivacaine versus levobupivacaine has any effects on the QTc interval during
      caesarean section. Sixty healthy pregnant women scheduled for elective caesarean
      section were randomized to spinal anaesthesia with either bupivacaine (the
      bupivacaine group) or levobupivacaine (the levobupivacaine group). ECG recordings
      were performed prior to spinal anaesthesia at baseline (T1), 5 min. after spinal
      anaesthesia, but before uterine incision (T2), and after skin closure (T3). QT
      intervals were calculated and corrected with the patients' heart rate according
      to the Bazett formula. Compared with baseline values, mean maximum QTc intervals
      at T2 and T3 were significantly longer in the levobupivacaine group, but only at
      T2 in the bupivacaine group. In addition, compared with the bupivacaine group,
      the QTc maximum interval at T3 was significantly longer in the levobupivacaine
      group. At T2, the QTc maximum intervals were longer than baseline in both groups.
      By the end of the surgery, the prolongation of the QTc interval had disappeared
      in the bupivacaine group but not in the levobupivacaine group.

PMID- 24118702
TI  - Ablation of breast cancer cells using trastuzumab-functionalized multi-walled
      carbon nanotubes and trastuzumab-diphtheria toxin conjugate.
AB  - Trastuzumab (Herceptin((r)) ) is a monoclonal antibody (mAb) for specific
      ablation of HER2-overexpressing malignant breast cancer cells. Intensification of
      antiproliferative activity of trastuzumab through construction of immunotoxins
      and nano-immunoconjugates is a promising approach for treatment of cancer. In
      this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also,
      conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were
      constructed by covalent immobilization of trastuzumab onto MWCNTs. Then,
      antiproliferative activity of the fusion constructs against HER2-overexpressing
      SK-BR-3 and also HER2-negative MCF-7 cancer cell lines were examined. Cells
      treated with trastuzumab-MWCNT conjugates were irradiated with near-infrared
      (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by
      MWCNTs can be resulted to thermal ablation of cancerous cells. Our results
      strongly showed that both trastuzumab-MWCNT and trastuzumab-DT conjugates were
      significantly efficient in the specific killing of SK-BR-3 cells. Targeting of
      MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR
      radiation was more efficient in repression of cell proliferation than treatment
      for cancer cells with trastuzumab-DT. Our results also showed that conjugation
      linkers can significantly affect the cytotoxicity of MWCNT-immunoconjugates. In
      conclusion, our data demonstrated that trastuzumab-MWCNT is a promising nano
      immunoconjugate for killing of HER2-overexpressing cancerous cells. 

PMID- 24118703
TI  - Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in
      patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3
      clinical trials.
AB  - BACKGROUND & AIMS: Triple therapy with peginterferon/ribavirin (PR) plus an NS3
      protease inhibitor has emerged as the standard-of-care for patients with chronic
      hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to
      boceprevir plus PR (BOC/PR) across three phase 2/3 studies. METHODS: SPRINT-1 was
      an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3
      studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure,
      RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC
      was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR
      and PR arms were combined for all three trials. The benefit of shortened duration
      of treatment using response-guided therapy (RGT) was also explored in the SPRINT
      2 trial. RESULTS: Only two adverse events, anaemia and dysgeusia, occurred 20%
      more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea
      and neutropenia were the only other common events with an incidence of at least
      5% greater when BOC was added to the PR backbone. The proportions of patients
      reporting serious adverse events (AE), life-threatening AEs, and study drug
      discontinuation because of an AE were similar in the PR and BOC/PR arms. In
      treatment-naive patients, RGT generally did not result in a lower frequency of
      common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a
      decrease in the mean duration of several clinically relevant AEs such as anaemia,
      neutropenia, fatigue and depression, as well as earlier normalization of
      haemoglobin and neutrophil counts. CONCLUSIONS: The safety profile of BOC
      combination therapy largely reflects the known profile of peginterferon and
      ribavirin, with incremental haematolgical effects and dysgeusia. Shorter
      treatment duration with RGT significantly reduced the duration of AEs.

PMID- 24118704
TI  - Age-dependent decline of beta-cell function in type 1 diabetes after diagnosis: a
      multi-centre longitudinal study.
AB  - AIMS: C-peptide secretion is currently the only available clinical biomarker to
      measure residual beta-cell function in type 1 diabetes. However, the natural
      history of C-peptide decline after diagnosis can vary considerably dependent upon
      several variables. We investigated the shape of C-peptide decline over time from
      type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c)
      levels and insulin dose. METHODS: We analysed data from 3929 type 1 diabetes
      patients recruited from seven European centres representing all age groups at
      disease onset (childhood, adolescence and adulthood). The influence of the age at
      onset on beta-cell function was investigated in a longitudinal analysis at
      diagnosis and up to 5-years follow-up. RESULTS: Fasting C-peptide (FCP) data at
      diagnosis were available in 3668 patients stratified according to age at
      diagnosis in four groups (<5 years, n = 344; >5 years < 10 years, n = 668; >10
      years < 18 years, n = 991; >18 years, n = 1655). FCP levels were positively
      correlated with age (p < 0.001); the subsequent decline in FCP over time was log
      linear with a greater decline rate in younger age groups (p < 0.0001).
      CONCLUSIONS: This study reveals a positive correlation between age at diagnosis
      of type 1 diabetes and FCP with a more rapid decline of beta-cell function in the
      very young patients. These data can inform the design of clinical trials using C
      peptide values as an end-point for the effect of a given treatment.

PMID- 24118705
TI  - Development of the Quality of Australian Nursing Documentation in Aged Care
      (QANDAC) instrument to assess paper-based and electronic resident records.
AB  - AIM: To develop an Australian nursing documentation in aged care (Quality of
      Australian Nursing Documentation in Aged Care (QANDAC)) instrument to measure the
      quality of paper-based and electronic resident records. METHODS: The instrument
      was based on the nursing process model and on three attributes of documentation
      quality identified in a systematic review. The development process involved five
      phases following approaches to designing criterion-referenced measures. The face
      and content validities and the inter-rater reliability of the instrument were
      estimated using a focus group approach and consensus model. RESULTS: The
      instrument contains 34 questions in three sections: completion of nursing history
      and assessment, description of care process and meeting the requirements of data
      entry. Estimates of the validity and inter-rater reliability of the instrument
      gave satisfactory results. CONCLUSION: The QANDAC instrument may be a useful
      audit tool for quality improvement and research in aged care documentation.

PMID- 24118706
TI  - Evaluating the students' perspectives of a clinic mentoring programme.
AB  - The purpose of this article is to describe and examine the effectiveness of a
      mentoring program for third and fourth year clinical dental students. This is an
      educational intervention for the pre-doctoral students at the Schulich School of
      Dentistry. We have recently instituted this program and have developed a
      questionnaire to assess the student perspectives using a SWOT analysis of the
      strengths, weaknesses, opportunities and threats of this intervention by
      analyzing the quantitative and qualitative responses of the students towards
      their clinical education and patient management. Our findings, both quantitative
      and qualitative, indicated that the mentoring program was well received by most
      students who would like to see the program expanded. The majority of students
      felt that the mentoring program aligned well with comprehensive care of their
      patients while enhancing their clinical experience. One of the strongest areas of
      agreement involved the ability to discuss cases in a non-threatening environment.
      The SWOT analysis identified key areas for future improvements. We offer steps to
      successfully implement a similar program based on our findings. It is our hope
      that our results might be instrumental for other schools wishing to adopt a
      similar model which supports patient-based comprehensive care. 

PMID- 24118707
TI  - The early development of human mirror mechanisms: evidence from electromyographic
      recordings at 3 and 6 months.
AB  - In primates and adult humans direct understanding of others' action is provided
      by mirror mechanisms matching action observation and action execution (e.g.
      Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing
      the existence of these mechanisms in the adult human brain, their origins and
      early development are largely unknown. In this study, for the first time,
      electromyographic (EMG) measures were used to shed light on the emergence of
      mirror motor mechanisms in infancy. EMG activity was recorded while 6- and 3
      month-old infants watched two videos displaying an agent reaching for, grasping
      and bringing an object either to the mouth or to the head. Results indicate that
      the motor system of 6-month-olds, but not 3-month-olds, was recruited and
      selectively modulated during observation of the goal-directed actions, favoring
      the idea that mirror mechanisms driving action understanding gradually emerge
      during early development. 

PMID- 24118708
TI  - From outcome prediction to action selection: developmental change in the role of
      action-effect bindings.
AB  - Ideomotor theory considers bidirectional action-effect associations to be the
      fundamental building blocks for intentional action. The present study employed a
      novel pupillometric and oculomotor paradigm to study developmental changes in the
      role of action-effects in the acquisition of voluntary action. Our findings
      suggest that both 7- and 12-month-olds (and adults) can use acquired action
      effect bindings to predict action outcomes but only 12-month-olds (and adults)
      showed evidence for employing action-effects to select actions. This dissociation
      supports the idea that infants acquire action-effect knowledge before they have
      developed the cognitive machinery necessary to make use of that knowledge to
      perform intentional actions. 

PMID- 24118710
TI  - Selective and faithful imitation at 12 and 15 months.
AB  - Research on imitation in infancy has primarily focused on what and when infants
      imitate. More recently, however, the question why infants imitate has received
      renewed attention, partly motivated by the finding that infants sometimes
      selectively imitate the actions of others and sometimes faithfully imitate, or
      overimitate, the actions of others. The present study evaluates the hypothesis
      that this varying imitative behavior is related to infants' social traits. To do
      so, we assessed faithful and selective imitation longitudinally at 12 and 15
      months, and extraversion at 15 months. At both ages, selective imitation was
      dependent on the causal structure of the act. From 12 to 15 months, selective
      imitation decreased while faithful imitation increased. Furthermore, infants high
      in extraversion were more faithful imitators than infants low in extraversion.
      These results demonstrate that the onset of faithful imitation is earlier than
      previously thought, but later than the onset of selective imitation. The observed
      relation between extraversion and faithful imitation supports the hypothesis that
      faithful imitation is driven by the social motivations of the infant. We call
      this relation the King Louie Effect: like the orangutan King Louie in The Jungle
      Book, infants imitate faithfully due to a growing interest in the interpersonal
      nature of interactions.

PMID- 24118711
TI  - Infants use social context to bind actions into a collaborative sequence.
AB  - Eye tracking was used to show that 18-month-old infants are sensitive to social
      context as a sign that others' actions are bound together as a collaborative
      sequence based on a joint goal. Infants observed five identical demonstrations in
      which Actor 1 moved a block to one location and Actor 2 moved the same block to a
      new location, creating a sequence of actions that could be considered either
      individual actions or collaboration. In the test phase, Actor 1 was alone and
      sitting so that she could reach both locations. The question was whether she
      would place a new block in the location she had previously (individual goal) or
      in the location that could be considered the goal of collaboration (joint goal).
      Importantly, in the Social condition, the actors were socially engaged with each
      other before and during the demonstration, while in the Non-Social condition,
      they were not. Results revealed that infants in the Social condition
      spontaneously anticipated Actor 1 placing her block in the joint goal location
      more often than those in the Non-Social condition. Thus, the social context seems
      to allow infants to bind actions into a collaborative sequence and anticipate
      joint rather than individual goals, giving insight into how actions are perceived
      using top-down processing early in life. 

PMID- 24118709
TI  - Fine motor skill predicts expressive language in infant siblings of children with
      autism.
AB  - We investigated whether fine motor and expressive language skills are related in
      the later-born siblings of children with autism (heightened-risk, HR infants) who
      are at increased risk for language delays. We observed 34 HR infants
      longitudinally from 12 to 36 months. We used parent report and standardized
      observation measures to assess fine motor skill from 12 to 24 months in HR
      infants (Study 1) and its relation to later expressive vocabulary at 36 months in
      HR infants (Study 2). In Study 1, we also included 25 infants without a family
      history of autism to serve as a normative comparison group for a parent-report
      fine motor measure. We found that HR infants exhibited fine motor delays between
      12 and 24 months and expressive vocabulary delays at 36 months. Further, fine
      motor skill significantly predicted expressive language at 36 months. Fine motor
      and expressive language skills are related early in development in HR infants,
      who, as a group, exhibit risk for delays in both. Our findings highlight the
      importance of considering fine motor skill in children at risk for language
      impairments and may have implications for early identification of expressive
      language difficulties.

PMID- 24118712
TI  - Play it again: neural responses to reunion with excluders predicted by attachment
      patterns.
AB  - Reunion behavior following stressful separations from caregivers is often
      considered the single most sensitive clue to infant attachment patterns.
      Extending these ideas to middle childhood/early adolescence, we examined
      participants' neural responses to reunion with peers who had previously excluded
      them. We recorded event-related potentials among nineteen 11- to 15-year-old
      youth previously classified on attachment interviews (11 secure and 8 insecure
      dismissing) while they played a virtual ball-toss game (Cyberball) with peers
      that involved fair play, exclusion and reunion phases. Compared to secure
      participants, dismissing participants displayed a greater increment in the N2
      during reunion relative to fair play, a neural marker commonly linked to
      expectancy violation. These data suggest a greater tendency toward continued
      expectations of rejection among dismissing children, even after cessation of
      social exclusion. In turn, the link between self-reported ostracism distress and
      neural signs of negative expectancy at reunion was moderated by attachment, such
      that self-reports were discordant with the neural index of expectancy violation
      for dismissing, but not for secure children.

PMID- 24118713
TI  - The development of stranger fear in infancy and toddlerhood: normative
      development, individual differences, antecedents, and outcomes.
AB  - Despite implications that stranger fear is an important aspect of developing
      behavioral inhibition, a known risk factor for anxiety, normative and atypical
      developmental trajectories of stranger fear across infancy and toddlerhood remain
      understudied. We used a large, longitudinal data set (N = 1285) including multi
      trait, multi-method assessments of temperament to examine the normative course of
      development for stranger fear and to explore the possibility that individual
      differences exist in trajectories of stranger fear development between 6 and 36
      months of age. A latent class growth analysis suggested four different
      trajectories of stranger fear during this period. Stable, high levels of stranger
      fear over time were associated with poorer RSA suppression at 6 months of age.
      Rates of concordance in trajectory-based class membership for identical
      (monozygotic) and fraternal (dizygotic) twins, along with associations between
      atypical stranger fear development and greater anxiety-related maternal
      characteristics, suggested that individual differences in developmental
      trajectories of stranger fear may be heritable. Importantly, trajectories of
      stranger fear during infancy and toddlerhood were linked to individual
      differences in behavioral inhibition, with chronically high levels of stranger
      fear and sharp increases in stranger fear over time related to greater levels of
      inhibition than other developmental trajectories.

PMID- 24118714
TI  - Domain-specific impulsivity in school-age children.
AB  - Impulsivity is a salient individual difference in children with well-established
      predictive validity for life outcomes. The current investigation proposes that
      impulsive behaviors vary systematically by domain. In a series of studies with
      ethnically and socioeconomically diverse samples of middle school students, we
      find that schoolwork-related and interpersonal-related impulsivity, as observed
      by teachers, parents, and the students themselves, are distinct, moderately
      correlated behavioral tendencies. Each demonstrates differentiated relationships
      with dimensions of childhood temperament, Big Five personality factors, and
      outcomes, such as report card grades. Implications for theoretical conceptions of
      impulsivity as well as for practical applications (e.g. domain-specific
      interventions) are discussed. 

PMID- 24118715
TI  - Of hissing snakes and angry voices: human infants are differentially responsive
      to evolutionary fear-relevant sounds.
AB  - Adult humans demonstrate differential processing of stimuli that were recurrent
      threats to safety and survival throughout evolutionary history. Recent studies
      suggest that differential processing of evolutionarily ancient threats occurs in
      human infants, leading to the proposal of an inborn mechanism for rapid
      identification of, and response to, evolutionary fear-relevant stimuli. The
      current study provides novel data in support of this proposal, showing for the
      first time that human infants differentially process evolutionary threats
      presented in the auditory modality. Sixty-one 9-month-olds listened to
      evolutionary fear-relevant, modern fear-relevant, and pleasant sounds, while
      their heart rate, startle, and visual orienting behaviours were measured. Infants
      demonstrated significantly enhanced heart rate deceleration, larger eye-blinks,
      and more visual orienting when listening to evolutionary fear-relevant sounds
      compared to sounds from the other two categories. These results support the
      proposal that human infants possess evolved mechanisms for the differential
      processing of a range of ancient environmental threats. 

PMID- 24118716
TI  - The neural correlates of processing newborn and adult faces in 3-year-old
      children.
AB  - The current study examines the processing of upright and inverted faces in 3-year
      old children (n = 35). Event-related potentials (ERPs) were recorded during a
      passive looking paradigm including adult and newborn face stimuli. We observed
      three face-sensitive components, the P1, the N170 and the P400. Inverted faces
      elicited shorter P1 latency and larger P400 amplitude. P1 and N170 amplitudes
      were larger for adult faces. To examine the role of experience in the development
      of face processing, the processing of adult and newborn faces was compared for
      children with a younger sibling (n = 23) and children without a younger sibling
      (n = 12). Age of sibling at test correlated negatively with P1 amplitude for
      adult and newborn faces. This may indicate more efficient processing of different
      face ages in children with a younger sibling and potentially reflects a more
      flexible face representation.

PMID- 24118717
TI  - Selective memories: infants' encoding is enhanced in selection via suppression.
AB  - The present study examined the hypothesis that inhibitory visual selection
      mechanisms play a vital role in memory by limiting distractor interference during
      item encoding. In Experiment 1a we used a modified spatial cueing task in which 9
      month-old infants encoded multiple category exemplars in the contexts of an
      attention orienting mechanism involving suppression (i.e. inhibition of return,
      IOR) versus one that does not (i.e. facilitation). At test, infants in the IOR
      condition showed both item-specific learning and abstraction of broader category
      information. In contrast, infants in the facilitation condition did not
      discriminate across novel and familiar test items. Experiment 1b confirmed that
      the learning observed in the IOR condition was specific to spatial cueing of
      attention and was not due to timing differences across the IOR and facilitation
      conditions. In Experiment 2, we replicated the results of Experiment 1, using a
      within-subjects design to explicitly examine learning and memory encoding in the
      context of concurrent suppression. These data show that developing inhibitory
      selective attention enhances efficacy of memory encoding for subsequent
      retrieval. Furthermore, these results highlight the importance of considering
      interactions between developing attention and memory systems. 

PMID- 24118718
TI  - White matter maturation supports the development of reasoning ability through its
      influence on processing speed.
AB  - The structure of the human brain changes in several ways throughout childhood and
      adolescence. Perhaps the most salient of these changes is the strengthening of
      white matter tracts that enable distal brain regions to communicate with one
      another more quickly and efficiently. Here, we sought to understand whether and
      how white matter changes contribute to improved reasoning ability over
      development. In particular, we sought to understand whether previously reported
      relationships between white matter microstructure and reasoning are mediated by
      processing speed. To this end, we analyzed diffusion tensor imaging data as well
      as data from standard psychometric tests of cognitive abilities from 103
      individuals between the ages of 6 and 18. We used structural equation modeling to
      investigate the network of relationships between brain and behavior variables.
      Our analyses provide support for the hypothesis that white matter maturation (as
      indexed either by microstructural organization or volume) supports improved
      processing speed, which, in turn, supports improved reasoning ability. 

PMID- 24118719
TI  - Young children care more about their reputation with ingroup members and
      potential reciprocators.
AB  - Human cooperation depends on individuals caring about their reputation, and so
      they sometimes attempt to manage them strategically. Here we show that even 5
      year-old children strategically manage their reputation. In an experimental
      setting, children shared significantly more resources with an anonymous recipient
      when (1) the child watching them could reciprocate later, and (2) the child
      watching them was an ingroup rather than an outgroup member (as established by
      minimal group markers). This study is not only the first to show that young
      children selectively invest in their reputation with specific individuals, but
      also the first to show that we care more about our reputation with ingroup than
      with outgroup members. 

PMID- 24118720
TI  - Statistical word learning at scale: the baby's view is better.
AB  - A key question in early word learning is how children cope with the uncertainty
      in natural naming events. One potential mechanism for uncertainty reduction is
      cross-situational word learning - tracking word/object co-occurrence statistics
      across naming events. But empirical and computational analyses of cross
      situational learning have made strong assumptions about the nature of naming
      event ambiguity, assumptions that have been challenged by recent analyses of
      natural naming events. This paper shows that learning from ambiguous natural
      naming events depends on perspective. Natural naming events from parent-child
      interactions were recorded from both a third-person tripod-mounted camera and
      from a head-mounted camera that produced a 'child's-eye' view. Following the
      human simulation paradigm, adults were asked to learn artificial language labels
      by integrating across the most ambiguous of these naming events. Significant
      learning was found only from the child's perspective, pointing to the importance
      of considering statistical learning from an embodied perspective. 

PMID- 24118721
TI  - Eye-voice span during rapid automatized naming of digits and dice in Chinese
      normal and dyslexic children.
AB  - We measured Chinese dyslexic and control children's eye movements during rapid
      automatized naming (RAN) with alphanumeric (digits) and symbolic (dice surfaces)
      stimuli. Both types of stimuli required identical oral responses, controlling for
      effects associated with speech production. Results showed that naming dice was
      much slower than naming digits for both groups, but group differences in eye
      movement measures and in the eye-voice span (i.e. the distance between the
      currently fixated item and the voiced item) were generally larger in digit-RAN
      than in dice-RAN. In addition, dyslexics were less efficient in parafoveal
      processing in these RAN tasks. Since the two RAN tasks required the same
      phonological output and on the assumption that naming dice is less practiced than
      naming digits in general, the results suggest that the translation of
      alphanumeric visual symbols into phonological codes is less efficient in dyslexic
      children. The dissociation of the print-to-sound conversion and phonological
      representation suggests that the degree of automaticity in translation from
      visual symbols to phonological codes in addition to phonological processing per
      se is also critical to understanding dyslexia. 

PMID- 24118722
TI  - Word-form familiarity bootstraps infant speech segmentation.
AB  - At about 7 months of age, infants listen longer to sentences containing familiar
      words - but not deviant pronunciations of familiar words (Jusczyk & Aslin, 1995).
      This finding suggests that infants are able to segment familiar words from fluent
      speech and that they store words in sufficient phonological detail to recognize
      deviations from a familiar word. This finding does not examine whether it is,
      nevertheless, easier for infants to segment words from sentences when these words
      sound similar to familiar words. Across three experiments, the present study
      investigates whether familiarity with a word helps infants segment similar
      sounding words from fluent speech and if they are able to discriminate these
      similar-sounding words from other words later on. Results suggest that word-form
      familiarity may be a powerful tool bootstrapping further lexical acquisition.

PMID- 24118723
TI  - Wheat genotypic variability in grain yield and carbon isotope discrimination
      under Mediterranean conditions assessed by spectral reflectance.
AB  - A collection of 368 advanced lines and cultivars of spring wheat (Triticum
      aestivum L.) from Chile, Uruguay, and CIMMYT (Centro Internacional de
      Mejoramiento de Maiz y Trigo), with good agronomic characteristics were evaluated
      under the Mediterranean conditions of central Chile. Three different water
      regimes were assayed: severe water stress (SWS, rain fed), mild water stress
      (MWS; one irrigation around booting), and full irrigation (FI; four irrigations:
      at tillering, flag leaf appearance, heading, and middle grain filling). Traits
      evaluated were grain yield (GY), agronomical yield components, days from sowing
      to heading, carbon isotope discrimination (Delta(13) C) in kernels, and canopy
      spectral reflectance. Correlation analyses were performed for 70 spectral
      reflectance indices (SRI) and the other traits evaluated in the three trials. GY
      and Delta(13) C were the traits best correlated with SRI, particularly when these
      indices were measured during grain filling. However, only GY could be predicted
      using a single regression, with Normalized Difference Moisture Index (NDMI2:
      2,200; 1,100) having the best fit to the data for the three trials. For Delta(13)
      C, only individual regressions could be forecast under FI (r(2): 0.25-0.37) and
      MWS (r(2): 0.45-0.59) but not under SWS (r(2): 0.03-0.09). NIR-based SRI proved
      to be better predictors than those that combine visible and NIR wavelengths.

PMID- 24118724
TI  - Diagnostic accuracy of a new cardiac electrical biomarker for detection of
      electrocardiogram changes suggestive of acute myocardial ischemic injury.
AB  - OBJECTIVE: A new cardiac "electrical" biomarker (CEB) for detection of 12-lead
      electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury
      has been identified. Objective was to test CEB diagnostic accuracy. METHODS: This
      is a blinded, observational retrospective case-control, noninferiority study. A
      total of 508 ECGs obtained from archived digital databases were interpreted by
      cardiologist and emergency physician (EP) blinded reference standards for
      presence of acute myocardial ischemic injury. CEB was constructed from three ECG
      cardiac monitoring leads using nonlinear modeling. Comparative active controls
      included ST voltage changes (J-point, ST area under curve) and a computerized ECG
      interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by
      receiver-operating-characteristic (ROC) analysis. Test set of 367 ECGs was
      analyzed for validation. Poor-quality ECGs were excluded. Sensitivity,
      specificity, and negative and positive predictive values were calculated with 95%
      confidence intervals. Adjudication was performed by consensus. RESULTS: CEB
      demonstrated noninferiority to all active controls by hypothesis testing. CEB
      adjudication demonstrated 85.3-94.4% sensitivity, 92.5-93.0% specificity, 93.8
      98.6% negative predictive value, and 74.6-83.5% positive predictive value. CEB
      was superior against all active controls in EP analysis, and against ST area
      under curve and ECGI by cardiologist. CONCLUSION: CEB detects acute myocardial
      ischemic injury with high diagnostic accuracy. CEB is instantly constructed from
      three ECG leads on the cardiac monitor and displayed instantly allowing immediate
      cost-effective identification of patients with acute ischemic injury during
      cardiac rhythm monitoring.

PMID- 24118725
TI  - HBV clinical isolates expressing adefovir resistance mutations show similar
      tenofovir susceptibilities across genotypes B, C and D.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) genotypes can influence clinical
      outcomes as well as response to antiviral therapy. This study evaluated the
      tenofovir (TFV) susceptibility of HBV genotype B, C and D clinical isolates with
      adefovir resistance-associated mutations (ADV-R). METHODS: Full-length HBV
      isolates from patients infected with genotype B, C and D virus had rtA181T,
      rtA181V, rtN236T, rtA181T+rtN236T and rtA181V+rtN236T mutations introduced by
      site-directed mutagenesis. Phenotypic analyses were performed in HepG2 cells and
      susceptibility to TFV and ADV were assessed. RESULTS: Clinical HBV isolates
      containing rtA181T, rtA181V or rtN236T as single mutants remained sensitive to
      TFV across genotypes B, C and D. Clinical isolates containing the rtA181T+rtN236T
      double mutant remained sensitive to TFV in genotype D but exhibited reduced
      susceptibility to TFV in genotypes B and C. Viruses containing the double mutant
      rtA181V+rtN236T in genotypes B and D exhibited reduced susceptibility to TFV with
      EC50 fold changes (FC) of 3.8 and 2.5, respectively, while genotype C viruses
      containing rtA181V+rtN236T either remained sensitive (FC=1.3) or exhibited
      reduced susceptibility to TFV (FC=2.9) depending on the isolate. All
      rtA181V+rtN236T isolates conferred reduced susceptibility to ADV (FC values 2.3
      4.2). CONCLUSIONS: Genotype B, C and D isolates with single ADV resistance
      mutations remained fully sensitive to TFV, while the double mutants
      rtA181T+rtN236T and rtA181V+rtN236T exhibited either no change or low-level
      reduced susceptibility to TFV across genotypes. These results are consistent with
      the clinical efficacy observed with tenofovir disoproxil fumarate (TDF) treatment
      across all genotypes in vivo and the limited impact of ADV-R mutations on TDF
      therapy.

PMID- 24118726
TI  - Overexpression of GmCaM4 in soybean enhances resistance to pathogens and
      tolerance to salt stress.
AB  - Plant diseases inflict heavy losses on soybean yield, necessitating an
      understanding of the molecular mechanisms underlying biotic/abiotic stress
      responses. Ca(2) (+) is an important universal messenger, and protein sensors,
      prominently calmodulins (CaMs), recognize cellular changes in Ca(2) (+) in
      response to diverse signals. Because the development of stable transgenic
      soybeans is laborious and time consuming, we used the Bean pod mottle virus
      (BPMV)-based vector for rapid and efficient protein expression and gene
      silencing. The present study focuses on the functional roles of the gene encoding
      the soybean CaM isoform GmCaM4. Overexpression of GmCaM4 in soybean resulted in
      enhanced resistance to three plant pathogens and increased tolerance to high salt
      conditions. To gain an understanding of the underlying mechanisms, we examined
      the potential defence pathways involved. Our studies revealed
      activation/increased expression levels of pathogenesis-related (PR) genes in
      GmCaM4-overexpressing plants and the accumulation of jasmonic acid (JA).
      Silencing of GmCaM4, however, markedly repressed the expression of PR genes. We
      confirmed the in vivo interaction between GmCaM4 and the CaM binding
      transcription factor Myb2, which regulates the expression of salt-responsive
      genes, using the yeast two-hybrid (Y2H) system and bimolecular fluorescence
      complementation assays. GmCaM4 and Glycine max CaM binding receptor-like kinase
      (GmCBRLK) did not interact in the Y2H assays, but the interaction between GmCaM2
      and GmCBRLK was confirmed. Thus, a GmCaM2-GmCBRLK-mediated salt tolerance
      mechanism, similar to that reported in Glycine soja, may also be functional in
      soybean. Confocal microscopy showed subcellular localization of the green
      fluorescent protein (GFP)-GmCaM4 fusion protein in the nucleus and cytoplasm.

PMID- 24118727
TI  - Guidelines in infectious diseases: how reliable are they?

PMID- 24118728
TI  - Typologies of professional identity among graduating baccalaureate-prepared
      nurses.
AB  - PURPOSE: The purpose of this study was to identify patterns of professional
      identity arising from the Quality and Safety Education for Nurses (QSEN)
      attitudes among students completing their prelicensure education. DESIGN: This
      mixed-method study used a modified Q-methodology design with a purposeful sample
      of 36 baccalaureate students graduating from three campuses of a large Midwestern
      university. Data were collected near the end of the spring semester of 2013.
      METHODS: Participants rank-ordered their agreement or disagreement with a set of
      subjective statements reflecting the 46 QSEN attitudes. Data were analyzed using
      a standard three-step approach that included generating a correlation matrix,
      completing factor analysis followed by varimax rotation, and calculating the
      factor scores. FINDINGS: Twenty statements represented consensus among the
      participants, and there was strong agreement that patient safety was both an
      individual and a team effort. Three professional identity typologies emerged:
      champions, collaborators, and individualists. CONCLUSIONS: Evidence was found
      that these students internalized the QSEN attitudes to varying degrees, but more
      work may be needed to internalize all attitudes, especially those related to
      patient-centered care. Future research is needed to evaluate how students with
      different perspectives transition to practice and to explore other factors that
      comprise professional identity. CLINICAL RELEVANCE: This study expands on what is
      known about patterns of professional identity among nurses and helps provide a
      beginning framework for understanding the values new graduates bring to practice.

PMID- 24118729
TI  - Tumour budding is a reproducible index for risk stratification of patients with
      stage II colon cancer.
AB  - AIM: High-risk patients with Stage II colon cancer may benefit from adjuvant
      chemotherapy, but it is difficult to identify such a patient group. A robust and
      reproducible index would be helpful to select the subset of Stage II colon cancer
      patients at high risk. This study investigated the potential prognostic
      significance of tumour budding in Stage II colon cancer. METHOD: In all, 135
      Stage II colon cancer patients with known outcome were identified. The degree of
      tumour budding was assessed by two individual observers and was classified,
      according to the number of tumour buds in the area with the greatest budding
      intensity on haematoxylin and eosin slides, as high-grade budding (10 or more
      tumour buds) and low-grade budding (0-9 buds). Inter-observer agreement for two
      observers was assessed by using the kappa test. Progression-free and cancer
      specific survivals were analysed using the Kaplan-Meier method and Cox
      regression. RESULTS: The 5-year progression-free survival rates for patients with
      high-grade tumour budding (n = 36) and those with low-grade budding (n = 99) were
      57.6% and 89.0% (P < 0.001). The 5-year cancer-specific survival rates were 66.7%
      vs 92.0% (P < 0.001). Cox regression analyses demonstrated tumour budding as an
      independent predictor of disease progression (hazard ratio 4.982, P < 0.001) and
      cancer-related death (hazard ratio 4.142, P = 0.003). The two observers agreed on
      the classification of tumour budding in 118 cases (87.4%) and the inter-observer
      agreement was good (kappa = 0.692). CONCLUSION: Tumour budding is a strong and
      reproducible prognostic factor for adverse outcome in Stage II colon cancer,
      which may serve as a prognostic marker to identify patients with a high risk of
      recurrence who may benefit from adjuvant therapy.

PMID- 24118730
TI  - Periodontal treatment reduces chronic systemic inflammation in peritoneal
      dialysis patients.
AB  - Chronic systemic inflammation, a non traditional risk factor of cardiovascular
      diseases, is associated with increasing mortality in chronic kidney disease,
      especially peritoneal dialysis patients. Periodontitis is a potential treatable
      source of systemic inflammation in peritoneal dialysis patients. Clinical
      periodontal status was evaluated in 32 stable chronic peritoneal dialysis
      patients by plaque index and periodontal disease index. Hematologic, blood
      chemical, nutritional, and dialysis-related data as well as highly sensitive C
      reactive protein were analyzed before and after periodontal treatment. At
      baseline, high sensitive C-reactive protein positively correlated with the
      clinical periodontal status (plaque index; r = 0.57, P < 0.01, periodontal
      disease index; r = 0.56, P < 0.01). After completion of periodontal therapy,
      clinical periodontal indexes were significantly lower and high sensitivity C
      reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood
      urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status
      improvement. Erythropoietin dosage requirement decreased from 8000 to 6000
      units/week while hemoglobin level was stable. Periodontitis is an important
      source of chronic systemic inflammation in peritoneal dialysis patients.
      Treatment of periodontal diseases can improve systemic inflammation, nutritional
      status and erythropoietin responsiveness in peritoneal dialysis patients. 

PMID- 24118731
TI  - Changes in hypertension treatment in the yaroslavl region of Russia: improvements
      observed between 2 cross-sectional surveys.
AB  - This prospective before-and-after survey of hypertensive patients visiting
      government-run outpatient health facilities in the Yaroslavl Region of Russia
      assessed blood pressure (BP)-related endpoints following initiation of a
      comprehensive health system improvement program for hypertension. Two cross
      sectional surveys, one at baseline and the other approximately 1 year after
      program initiation, evaluated the primary measure of BP control rate. Secondary
      measures included mean BP levels and distribution, cardiovascular risk factors,
      and associated conditions, heart rate levels, and antihypertensive therapy. From
      the 2011 survey (n=1794) to the 2012 survey (n=2992), BP control rate (<140/90 mm
      Hg) significantly increased from 16.8% to 23.0%, reflecting a 37% relative
      improvement (P<.0001). Mean BP level was significantly reduced from 151/90 mm Hg
      to 147/88 mm Hg (P<.0001). Severe uncontrolled hypertension (systolic BP >=180 mm
      Hg) was reduced from 9.7% to 6.4% (P<.0001). Implementing a guidelines-based
      treatment protocol with medical and patient education programs resulted in
      physician behavior change and improved patient BP control. 

PMID- 24118732
TI  - Supporting public involvement in research design and grant development: a case
      study of a public involvement award scheme managed by a National Institute for
      Health Research (NIHR) Research Design Service (RDS).
AB  - BACKGROUND: It is good practice for the public to be involved in developing
      health research. Resources should be available for researchers to fund the
      involvement of the public in the development of their grants. OBJECTIVE: To
      describe a funding award scheme to support public involvement in grant
      development, managed by an NIHR Research Design Service (RDS). Case examples of
      how the award contributed to successful grant applications and findings from a
      recent evaluation of the scheme are presented. DESIGN: A case study of resource
      provision to support public involvement activities in one region of England.
      PARTICIPANTS: University and NHS-based researchers, and members of the public.
      FINDINGS: Between 2009 and 2012, the RDS approved 45 public involvement funding
      awards (totalling nearly L19,000). These awards contributed to 27 submitted
      applications at the time of writing, of which 11 were successful (totalling over
      L7.5 million). The evaluation revealed difficulties encountered by some
      researchers when involving the public in grant development, which led to
      suggestions about how the scheme could be improved. CONCLUSION: This award scheme
      represents an efficient method of providing researchers with resources to involve
      the public in grant development and would appear to represent good value for
      money.

PMID- 24118734
TI  - Prediction of human pharmacokinetics from preclinical information of rhein, an
      antidiabetic nephropathy drug, using a physiologically based pharmacokinetic
      model.
AB  - The aim of the study was to develop a physiologically based pharmacokinetic
      (PBPK) model of rhein to predict human pharmacokinetics before dosing for the
      first time in human beings. After oral administration of rhein at the doses of
      35, 70 and 140 mg/kg in rat, rhein had the following mean plasma pharmacokinetic
      properties: t1/2 of 3.2, 3.6 and 4.3 hr, AUCinfinity of 69.5, 164.3 and 237.8
      MUg/h/ml and CL/F of 503.4, 426.1 and 588.8 ml/hr/kg, respectively. In vitro, the
      intrinsic clearance (Clint ) of rhein in cytochrome P450 (CYP450), UDP
      glucuronosyltransferase (UGT) and sulfotransferase (SULT) metabolism of rat was
      0.6, 7.8, and 5.5 MUl/min/mg protein, respectively. The Clint of rhein in CYP450,
      UGT and SULT of human beings was 0.10, 1.36 and 0.68 MUl/min/mg protein. The rat
      pharmacokinetics and the metabolism data in vitro were used to construct the PBPK
      model of rhein, and the observed plasma drug concentration profiles of rhein in
      rat were validated by a PBPK model. Subsequently, the plasma drug concentration
      profiles of human beings by the present PBPK model were validated by experimental
      data in human beings accurately.

PMID- 24118733
TI  - Effect of HA14-1 on apoptosis-regulating proteins in HeLa cells.
AB  - Overexpression of Bcl-2 has been recognized in various malignancies. Recently,
      HA14-1, a Bcl-2 antagonist, has been identified for its anti-apoptotic effect.
      However, mode of action of HA14-1 still remains to be elucidated. In this study,
      we examined HA14-1 binding efficiency with receptor proteins through molecular
      docking. Cell viability using HeLa cells was evaluated through MTT assay after
      exposure to different concentration of HA14-1. Moreover, after HA14-1 exposure,
      expressions of tumor suppressor protein (p53), BH3-only protein (Puma) and
      apoptosis-associated proteins were analyzed by Western blotting. From the
      results, it was found that HA14-1 occupied all three domains; BH1, BH2, and BH3
      within the hydrophobic pocket of Bcl-2. However, HA14-1 occupied only BH1 and BH3
      of Bcl-xl, conversely, no such stable bond was observed for Bax and Bak. ARG107
      and TYR101 were the amino acids involved in the binding of HA14-1 to Bcl-2 and
      Bcl-xl, respectively. Additionally, decrease in Bcl-2 and Bcl-xl expression along
      with increase in p53 and Puma expression after exposure to HA14-1 was observed.
      The results suggested p53 pathway to be the probable mechanism of action for the
      induction of apoptosis in HeLa cell by downregulating the effect of anti
      apoptotic proteins suggesting that HA14-1 may provide therapeutic potential for
      the treatment of human cervical cancer. 

PMID- 24118735
TI  - An affordable method to obtain cultured endothelial cells from peripheral blood.
AB  - The culture of endothelial progenitor cells (EPC) provides an excellent tool to
      research on EPC biology and vascular regeneration and vasculogenesis. The use of
      different protocols to obtain EPC cultures makes it difficult to obtain
      comparable results in different groups. This work offers a systematic comparison
      of the main variables of most commonly used protocols for EPC isolation, culture
      and functional evaluation. Peripheral blood samples from healthy individuals were
      recovered and mononuclear cells were cultured. Different recovery and culture
      conditions were tested: blood volume, blood anticoagulant, coating matrix and
      percentage of foetal bovine serum (FBS) in culture media. The success of culture
      procedure, first colonies of endothelial cells appearance time, correlation with
      number of circulating EPC (cEPC) and functional comparison with human umbilical
      vein endothelial cells (HUVEC) were studied. The use of heparin, a minimum blood
      volume of 30 ml, fibronectin as a coating matrix and endothelial growing media-2
      supplemented with 20% FBS increased the success of obtaining EPC cultures up to
      80% of the processed samples while reducing EPC colony appearance mean time to a
      minimum of 13 days. Blood samples exhibiting higher cEPC numbers resulted in
      reduced EPC colony appearance mean time. Cells isolated by using this combination
      were endothelial cell-like EPCs morphological and phenotypically. Functionally,
      cultured EPC showed decreased growing and vasculogenic capacity when compared to
      HUVEC. Thus, above-mentioned conditions allow the isolation and culture of EPC
      with smaller blood volumes and shorter times than currently used protocols. 

PMID- 24118736
TI  - Association of run-in periods with weight loss in obesity randomized controlled
      trials.
AB  - Study-level design characteristics that inform the optimal design of obesity
      randomized controlled trials (RCTs) have been examined in few studies. A pre
      randomization run-in period is one such design element that may influence weight
      loss. We examined 311 obesity RCTs published between 1 January 2007 and 1 July
      2009 that examine d weight loss or weight gain prevention as a primary or
      secondary end-point. Variables included run-in period, pre-post intervention
      weight loss, study duration (time), intervention type, percent female and degree
      of obesity. Linear regression was used to estimate weight loss as a function of
      (i) run-in (yes/no) and (ii) run-in, time, percent female, body mass index and
      intervention type. Interaction terms were also examined. Approximately 19%
      (18.6%) of the studies included a run-in period, with pharmaceutical studies
      having the highest frequency. Although all intervention types were associated
      with weight loss (Mean = 2.80 kg, SD = 3.52), the inclusion of a pre
      randomization run-in was associated with less weight loss (P = 0.0017) compared
      with studies that did not include a run-in period. However, this association was
      not consistent across intervention types. Our results imply that in trials
      primarily targeting weight loss in adults, run-in periods may not be beneficial
      for improving weight loss outcomes in interventions.

PMID- 24118738
TI  - Prevalence of aggressive challenging behaviours in intellectual disability and
      its relationship to personality status: Jamaican study.
AB  - BACKGROUND: Both the classification of personality disorder in intellectual
      disability (ID) and its identification in practice are deemed to be difficult. A
      simpler approach to classification and its relationship to challenging behaviours
      were tested in an adult Jamaican population with ID. METHOD: The study was
      carried out in Kingston, Jamaica, as part of a programme of field trials to
      determine the utility of the proposed revision of personality disorders in the
      11th Revision of the International Classification of Diseases (ICD-11), in a
      population of adults with ID living with their families or in supported care
      homes. Thirty-eight people with borderline (n = 5), mild (n = 16), moderate (n =
      14) and severe (n = 3) ID were assessed at face-to-face interview and with
      relatives or staff using the provisional criteria for severity of personality
      disorder and its associated domain traits, and challenging behaviour was assessed
      using the Problem Behaviour Check List (PBCL) (a 5-point, 7-item scale). RESULTS:
      Using the severity scale 18 patients (47%) had no personality disorder, 7 (18%)
      had personality difficulty, 9 (24%) had mild personality disorder, and 4 (11%)
      had moderate personality disorder. None of the sample had severe personality
      disorder in which there is high risk of harm to self or others. Of the four major
      trait domains, provisionally named anankastic, detached, emotional and dissocial,
      three were evenly distributed in those with personality disturbance with the
      antagonistic (antisocial) trait less commonly shown (6 only). Scores on the PBCL
      were higher in those with increasing severity of personality disorder (P = 0.03)
      and those in the antagonistic personality trait domain had the highest PCL
      scores. CONCLUSIONS: Despite previous difficulties in assessing personality
      disorder in intellectual difficulties the ICD-11 classification was easy to
      administer in practice in this population, and the higher problem behaviour
      scores in those with greater severity of personality disturbance support its
      construct validity.

PMID- 24118739
TI  - Diet alters probiotic Lactobacillus persistence and function in the intestine.
AB  - We investigated the effects of host diet on the intestinal persistence and gene
      expression of Lactobacillus plantarum WCFS1 in healthy and health-compromised,
      2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Mice fed either a low
      fat chow diet (CD) or high fat and sucrose Western diet (WD) received 10(9) L.
      plantarum WCFS1 cells for five consecutive days. Lactobacillus plantarum
      persistence was 10- to 100-fold greater in the intestines of WD-fed compared with
      CD-fed mice. TNBS, an intestinal irritant that induces the development of
      inflammatory bowel disease-like symptoms, resulted in up to a 10(4) -fold
      increase in L. plantarum survival in the digestive tract relative to healthy
      animals. Expression levels of 12 metabolic and gut-inducible L. plantarum genes
      were differentially affected by diet and TNBS administration. Pyrosequencing of
      16S rRNA transcripts from the indigenous intestinal microbiota showed that WD
      resulted in significant reductions in proportions of metabolically active
      indigenous Lactobacillus species and increases in the Desulfovibrionaceae family.
      Feeding L. plantarum WCFS1 resulted in lower levels of colitis and higher
      concentrations of colonic IL-10 and IL-12 in WD and not CD-fed mice. Interactions
      between probiotics, nutritional components and the intestinal bacteria should be
      considered when examining for probiotic-mediated effects and elucidating
      mechanisms of probiotic function in the mammalian gut. 

PMID- 24118740
TI  - Activity restriction and the mechanistic basis for extinctions under climate
      warming.
AB  - Correlative analyses predict that anthropogenic climate warming will cause
      widespread extinction but the nature and generality of the underlying mechanisms
      is unclear. Warming-induced activity restriction has been proposed as a general
      explanatory mechanism for recent population extinctions in lizards, and has been
      used to forecast future extinction. Here, I test this hypothesis using globally
      applied biophysical calculations of the effects of warming and shade reduction on
      potential activity time and whole-life-cycle energy budgets. These 'thermodynamic
      niche' analyses show that activity restriction from climate warming is unlikely
      to provide a general explanation of recent extinctions, and that loss of shade is
      viable alternative explanation. Climate warming could cause population declines,
      even under increased activity potential, through joint impacts on fecundity and
      mortality rates. However, such responses depend strongly on behaviour, habitat
      (shade, food) and life history, all of which should be explicitly incorporated in
      mechanistic forecasts of extinction risk under climate change. 

PMID- 24118741
TI  - Nanosecond-laser application in intermediate AMD: 12-month results of fundus
      appearance and macular function.
AB  - BACKGROUND: A novel, ultra-low energy nanosecond laser (retinal rejuvenation
      therapy) has been developed with the aim to slow progression of early age-related
      macular degeneration (AMD). The safety, changes in fundus characteristics and
      macular function in a cohort of participants with bilateral intermediate AMD are
      reported. DESIGN: Prospective non-randomised, pilot intervention study.
      PARTICIPANTS OR SAMPLES: Subjects with bilateral intermediate AMD (n = 50, aged
      50-75 years). METHODS: Ultra-low energy laser pulses applied in 12 spots around
      the macula of one eye (0.15-0.45 mJ), using 400 MUm diameter spot, 3 nanosecond
      pulse length, 532 nm wavelength and energy titrated to each patient. MAIN OUTCOME
      MEASURES: Best corrected visual acuity, drusen area and macular sensitivity
      (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser. RESULTS:
      Treatment was painless with no clinically visible lesions. No participant
      developed choroidal neovascularization, while two with thin central retinal
      thickness at baseline developed atrophy at 12-month follow up. Drusen area was
      reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in
      drusen and function not being coincident. Improvement in flicker threshold within
      the central 3 degrees  was observed in both the treated and untreated fellow eyes
      at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker
      defect >15 dB), seven improved sufficiently to be taken out of this high-risk
      category. CONCLUSIONS: A single unilateral application of nanosecond laser to the
      macula produced bilateral improvements in macula appearance and function. The
      nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an
      early intervention for AMD.

PMID- 24118742
TI  - Perinatal complications of monochorionic diamniotic twin gestations with
      discordant crown-rump length determined at mid-first trimester.
AB  - AIM: The aim of this study was to investigate the value of discordance of crown
      rump length (DCRL) at mid-first trimester to predict adverse outcomes in
      monochorionic diamniotic twin gestations (MD). MATERIAL AND METHODS: This was a
      retrospective cohort study of the perinatal outcome in MD pregnancies managed
      from the first trimester onward. DCRL was evaluated between 8 and 10 weeks of
      gestation. The association between DCRL and perinatal complications, including
      fetal death, twin-twin transfusion syndrome, severe discordant birthweight (DB),
      and twin anemia-polycythemia sequence, was assessed. RESULTS: Among 126 cases, a
      single fetal demise occurred in two (2%) and demise of both fetuses occurred in
      eight (6%). Five pregnancies (4%) were complicated with twin-twin transfusion
      syndrome; one case (1%) was twin anemia-polycythemia sequence and 13 (10%) were
      DB. Neonatal death occurred in one pair. At 28 days of age, in 115 cases (91%)
      both twins were alive. In 117 cases (93%), at least one twin survived until 28
      days of age. DCRL >12.0% was not related to any perinatal complications but DB (P
      < 0.01; relative risk: 1.40; 95% confidence interval: 1.06-1.84). CONCLUSIONS:
      DCRL in MD during the mid-first trimester might be useful for predicting DB.

PMID- 24118745
TI  - A short motif in the N-terminal part of the coat protein is a host-specific
      determinant of systemic infectivity for two potyviruses.
AB  - Although the biological variability of Watermelon mosaic virus is limited,
      isolates from the three main molecular groups differ in their ability to infect
      systemically Chenopodium quinoa. Mutations were introduced in a motif of three or
      five amino acids located in the N-terminal part of the coat protein, and
      differing in isolates from group 1 (motif: lysine-glutamic acid-alanine (Lys-Glu
      Ala) or KEA, systemic on C. quinoa), group 2 (Lys-Glu-Thr or KET, not systemic on
      C. quinoa) and group 3 (KEKET, not systemic on C. quinoa). Mutagenesis of KEKET
      in an isolate from group 3 to KEA or KEKEA was sufficient to make the virus
      systemic on C. quinoa, whereas mutagenesis to KET had no effect. Introduction of
      a KEA motif in Zucchini yellow mosaic virus coat protein also resulted in
      systemic infection on C. quinoa. These mutations had no obvious effect on the
      disorder profile or potential post-translational modifications of the coat
      protein as determined in silico.

PMID- 24118744
TI  - Intraocular and periocular lymphoma in dogs and cats: a retrospective review of
      21 cases (2001-2012).
AB  - OBJECTIVE: To immunologically phenotype and histologically classify canine and
      feline intraocular and periocular lymphomas. METHODS: The databases of four
      veterinary medical diagnostic laboratories were searched to identify cases of
      intraocular or periocular lymphoma in dogs and cats between 2001 and 2012.
      Hematoxylin and eosin (H&E) stained slides were reviewed for confirmation and
      classification of lymphoma, and immunohistochemistry for CD3 (T-cell marker) and
      CD79a and/or CD20 (B-cell markers) was examined to determine the lineage of the
      neoplastic lymphocytes. RESULTS: Six canine and 15 feline cases of ocular
      lymphoma were identified. In the canine cases, there were three intraocular and
      three periocular lymphomas where two intraocular and one periocular lymphomas
      were B-cell, one of each intraocular and periocular lymphomas were T-cell and one
      periocular lymphoma was nonreactive with CD3, CD79a or CD20. In the feline cases,
      there were six intraocular and nine periocular lymphomas where five intraocular
      and six periocular lymphomas were B-cell, and one intraocular and three
      periocular lymphomas were T-cell. Only one canine case had concurrent generalized
      lymphadenopathy, only one canine conjunctival lymphoma had simultaneous cutaneous
      lymphoma, and only one feline case had bilateral ocular involvement when they
      were diagnosed. CONCLUSION: Canine and feline intraocular and periocular
      lymphomas are often of B-cell phenotype. Although in general terms lymphoma is
      not considered a primary tumor when it occurs in or adjacent to the globe, these
      tumors frequently first become evident in the globe and/or periocular area. An
      accurate early diagnostic approach is crucial for the patient's quality of life
      because B-cell lymphomas are generally more amenable to chemotherapy than T-cell
      lymphomas.

PMID- 24118743
TI  - Hypovitaminosis D is associated with increased whole body fat mass and greater
      severity of non-alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Hypovitaminosis D is common in obesity and insulin-resistant
      states. Increased fat mass in patients with non-alcoholic fatty liver disease
      (NAFLD) may contribute to hypovitaminosis D. To determine the relation among
      plasma vitamin D concentration, severity of disease and body composition in
      NAFLD. METHODS: Plasma vitamin D concentration was quantified in 148 consecutive
      biopsy-proven patients with NAFLD (non-alcoholic steatohepatitis - NASH: n = 81;
      and hepatic steatosis: n = 67) and healthy controls (n = 39). NAFLD was scored
      using the NASH CRN criteria. Body composition was quantified by bioelectrical
      impedance analysis and abdominal CT image analysis. RESULTS: Plasma vitamin D
      concentration was significantly lower in NAFLD (21.2 +/- 10.4 ng/ml) compared
      with healthy controls (35.7 +/- 6.0 ng/ml). Higher NAFLD activity scores were
      associated with lower plasma concentration of vitamin D (r(2)  = 0.29; P <
      0.001). Subgroup analysis among patients with NAFLD showed that patients with
      NASH had significantly lower (P < 0.01) vitamin D levels than those with
      steatosis alone (18.1 +/- 8.4 vs. 25.0 +/- 11.3 ng/ml). Low concentrations of
      vitamin D were associated with greater severity of steatosis, hepatocyte
      ballooning and fibrosis (P < 0.05).On multivariate regression analysis, only
      severity of hepatocyte ballooning was independently associated (P = 0.02) with
      low vitamin D concentrations. Plasma vitamin D (P = 0.004) and insulin
      concentrations (P = 0.03) were independent predictors of the NAFLD activity score
      on biopsy. Patients with NAFLD had higher fat mass that correlated with low
      vitamin D (r(2)  = 0.26; P = 0.008). CONCLUSIONS: Low plasma vitamin D
      concentration is an independent predictor of the severity of NAFLD. Further
      prospective studies demonstrating the impact of vitamin D replacement in NAFLD
      patients are required.

PMID- 24118746
TI  - Successful clinical and organisational change in endodontic practice: a
      qualitative study.
AB  - The aim of this study was to explicate and describe the qualitative meaning of
      successful clinical and organizational change in endodontic practice, following a
      comprehensive implementation program, including the integration of the nickel
      titanium-rotary-technique. After an educational intervention in the Public Dental
      Service in a Swedish county, thematic in-depth interviews were conducted, with
      special reference to the participants' experience of the successful change.
      Interviews with four participants, were purposively selected on the basis of
      occupation (dentist, dental assistant, receptionist, clinical manager), for a
      phenomenological human scientific analysis. Four constituents were identified as
      necessary for the invariant, general structure of the phenomenon: 1) disclosed
      motivation, 2) allowance for individual learning processes, 3) continuous
      professional collaboration, and 4) a facilitating educator. The perceived
      requirements for achieving successful clinical and organizational change in
      endodontic practice were clinical relevance, an atmosphere which facilitated
      discussion and allowance for individual learning patterns. The qualities required
      in the educator were acknowledged competence with respect to scientific knowledge
      and clinical expertise, as well as familiarity with conditions at the dental
      clinics. The results indicate a complex interelationship among various aspects of
      the successful change process. 

PMID- 24118747
TI  - HBsAg quantification for identification of liver disease in chronic hepatitis B
      virus carriers.
AB  - BACKGROUND & AIMS: Quantification of hepatitis B surface antigen (HBsAg) has been
      proposed as a useful diagnostic marker for clinical staging (identification of
      inactive carrier state) and prognosis of chronic hepatitis B virus (HBV)
      infection. The aim of this study was to investigate the correlation between HBsAg
      levels in serum and histological liver damage in patients with chronic infection.
      METHODS: HBsAg levels in serum (by Abbott Architect) were related to HBV DNA, ALT
      and histological score (n=160) and covalently closed circular DNA (cccDNA)
      (n=84). RESULTS: HBsAg levels correlated with cccDNA, serum HBV DNA, ALT and high
      inflammation scores (P<0.001). Among HBeAg-negative patients, an HBsAg level
      below 3.0 log10 IU/ml identified minimal liver damage (normal ALT and mild
      inflammation) with a predictive value of 92% (alone) or 96% (in combination with
      HBV DNA<4.0 log10 copies/ml), whereas an HBsAg level above 3.5 log10 IU/ml
      identified severe inflammation with a predictive value of 16% (alone) or 33% (in
      combination with HBV DNA>5.0 log10 copies/ml). CONCLUSIONS: HBsAg levels reflect
      clinical stage and liver disease, and a combined quantification of HBsAg and HBV
      DNA may improve clinical staging.

PMID- 24118748
TI  - Validity of a self-administered diet history questionnaire for estimating vitamin
      D intakes of Japanese pregnant women.
AB  - Maternal vitamin D status is important for fetal development and the prevention
      of pregnancy complications. Mothers require both sufficient intakes and skin
      production of this vitamin. We investigated the validity and test-retest
      reliability of a self-administered diet history questionnaire (DHQ) to establish
      a method of assessing vitamin D intakes of Japanese pregnant women, using a serum
      marker. A total of 245 healthy pregnant women in the second trimester, who were
      not taking vitamin D supplements, were recruited at a university hospital in
      Tokyo between June 2010 and July 2011. Serum 25-hydroxyvitamin D [25(OH)D]
      concentrations were measured as an indicator of vitamin D status. To assess the
      test-retest reliability of the DHQ, 58 pregnant women completed it twice within a
      4-5-week interval. Significant positive correlations between intakes and serum
      concentrations of vitamin D were found (r = 0.266 for daily intakes and r = 0.249
      for energy-adjusted intakes). In the winter investigation in which the serum
      25(OH)D concentrations were less likely to be affected by sunlight exposure, the
      correlation coefficients were 0.304 for both daily and energy-adjusted intakes.
      After excluding participants with pregnancy-associated nausea, the coefficients
      increased. The intraclass correlation coefficient between vitamin D intakes
      estimated from the two-time DHQ was 0.638. The DHQ provides an acceptable
      validity and reliability of the vitamin D intake of Japanese pregnant women.
      However, the data of women with nausea should be interpreted with caution. We
      believe that the DHQ is a useful questionnaire to grasp and improve vitamin D
      intakes during pregnancy. 

PMID- 24118749
TI  - Postpartum women's sleep quality and its predictors in Taiwan.
AB  - PURPOSE: The purpose of this study was to explore postpartum women's sleep
      quality and its predictors in Taiwan. DESIGN: Cross-sectional design. METHODS:
      Postpartum women (N = 327) were recruited during their postnatal check-ups in
      Taiwan. Data were collected from October 2008 to July 2009 using a demographic
      form, the Pittsburgh Sleep Quality Index (PSQI), Physical Symptoms Checklist,
      Perceived Stress Scale, and Postpartum Social Support Scale. Descriptive
      statistics, Pearson's correlation, and stepwise multiple regression analysis were
      used to analyze data. RESULTS: Most participants (87.5%) reported poor sleep
      quality (PSQI > 5). Postpartum sleep quality was predicted by postpartum physical
      symptoms, frequency of nighttime awakening, co-sleeper disturbance, marital
      satisfaction, perceived stress, and baby sleep status, which explained 29.9% of
      the total variance. CONCLUSIONS: Most postpartum women did not sleep well due to
      physical discomfort, perceived stress, co-sleeper disturbance, and marital
      dissatisfaction. CLINICAL RELEVANCE: Evaluation of sleep quality should be a
      routine part of postnatal check-ups. Information on women's sleep problems,
      marital satisfaction, stress, co-sleepers, and baby sleep status can be used to
      individualize intervention protocols for sleep-disturbed women.

PMID- 24118750
TI  - The effect of weight loss on health-related quality of life: systematic review
      and meta-analysis of randomized trials.
AB  - The aim of this study was to examine the effect of weight loss on health-related
      quality of life (HRQL) in randomized controlled intervention trials (RCTs).
      MEDLINE, HealthStar and PsycINFO were searched. RCTs of any weight loss
      intervention and 20 HRQL instruments were examined. Contingency tables were
      constructed to examine the association between statistically significant weight
      loss and statistically significant HRQL improvement within five HRQL categories.
      In addition, Short Form-36 (SF-36) outcomes were pooled using random-effects
      models. Fifty-three trials were included. Seventeen studies reported
      statistically significant weight loss and HRQL improvement. No statistically
      significant associations between weight loss and HRQL improvement were found in
      any contingency table. Because of suboptimal endpoint reporting, quantitative
      data pooling could only be performed using 25% of SF-36 trials in any one model.
      Significant improvements in physical health were found: mean difference 2.83
      points, 95% CI 0.55-5.1, for the physical component score, and mean difference
      6.81 points, 95% CI 2.99-10.63, for the physical functioning domain score.
      Conversely, no significant improvements in mental health were found. No
      significant association was found between weight loss and overall HRQL
      improvement. Weight loss may be associated with modest improvements in physical,
      but not mental, health. 

PMID- 24118751
TI  - Will baby boomers create new models of retirement community in rural Australia?
AB  - AIM: Baby boomers are depicted as a cohort who will redefine the ageing process
      and reject segregated homes for older people. This exploratory study sought to
      find and interview friendship groups in rural Australia who are actively engaged
      in creating alternative living arrangements conceptualised around preparations
      for old age. METHOD: A purposive sampling frame and snowballing techniques were
      used to identify groups of interest, who were interviewed by phone using a
      semistructured survey. RESULTS: Five groups were identified, each with explicit
      plans to avoid segregated housing by taking care of each other. They believe
      segregated housing to be undesirable and unsustainable, and perceive a need for
      alternative solutions. CONCLUSIONS: Baby boomers geographically unattached and
      independent of children recognise they will require the cooperation of others to
      remain independent for as long as possible, and will strive to create mutually
      supportive living arrangements - thus creating new models of retirement
      community.

PMID- 24118752
TI  - 'Too much for one day': a case study of disclosure in the paediatric HIV/AIDS
      clinic.
AB  - BACKGROUND: Despite acknowledgement of the complexity and challenges of the
      process of disclosure of HIV status to adolescents, little work has been carried
      out on the communication features which facilitate or hinder the process. This
      qualitative case study reflects the interactional dynamics of an interaction
      between caregiver, physician and counsellor around the topic of disclosure in a
      South African clinic. METHODS: A 40-minute encounter between a doctor, the
      grandmother of an adolescent with HIV/AIDS and a counsellor around the process of
      disclosure was transcribed and examined in detail in relation to its structure,
      topics, timing and sequence as well as its movement towards a collaborative
      ending. Analysis was based on elements of conversational and thematic analysis.
      RESULTS: The session was characterized by distinct stages and the emergence of
      multiple voices and perspectives from the participants. The negotiated management
      of the session sheds light on multiple barriers to care as well as the influence
      of contextual factors on the process. The important mediating role of the
      counsellor in the triad emerges. The analysis highlights both unique features of
      the consultation and common challenges to clinicians when disclosing. DISCUSSION
      AND CONCLUSIONS: The task of disclosure is complex and intricate. Results suggest
      team processes are critical, as are temporal and contextual factors and the need
      for an understanding of communication. Implications for the clinic team are
      discussed and suggestions made for the development of collaborative partnership
      based on an understanding of roles and responsibilities, time factors and
      enhancement of features such as trust and communication.

PMID- 24118753
TI  - Sudden death due to nonarrhythmic cause in a patient with L-TGA.
AB  - We report a case of sudden death in a clinically stable adult with l
      transposition of the great arteries (l-TGA). Sudden death has been reported to be
      the leading cause of death in l-TGA and is often attributed to arrhythmias in the
      absence of another identifiable cause. However, the contribution of nonarrhythmic
      causes to the burden of sudden death in this population is unknown. Comprehensive
      postmortem investigation, including autopsy and pacemaker interrogation,
      demonstrated that the cause of death was massive pulmonary hemorrhage due to
      stenosis of the patient's mechanical tricuspid (systemic AV) valve. This report
      highlights the important contribution of nonarrhythmic causes of sudden death in
      this population and the value of autopsy and device interrogation in determining
      true cause of death.

PMID- 24118754
TI  - Clinical evaluation of improvised gauze-based negative pressure wound therapy in
      military wounds.
AB  - The use of negative pressure wound therapy (NPWT) in civilian and military wounds
      is found effective in promoting granulation tissue, decreasing exudate and
      improving patient comfort. The Use of gauze-based NPWT is increasing in civilian
      trauma cases with availability of proprietary systems using gauze as filler
      material rather than the traditionally used reticulated open-cell foam. Military
      trauma wounds differ from civilian trauma wounds in energy of impact, degree and
      nature of contamination as well as the hostile environments. The Use of gauze as
      filler material for NPWT in military trauma wounds is less well studied. This
      study is a retrospective analysis of use of improvised gauze-based NPWT in
      military trauma wounds. The whole assembly was constructed from commonly
      available operation theatre supplies and no proprietary system was used. Results
      were very encouraging and the use of this improvised method can be useful and
      cheap alternative to costly proprietary systems. 

PMID- 24118755
TI  - What can waterpipe tobacco smoking teach us about the need for a more rapid
      response to emerging non-communicable disease risks?

PMID- 24118756
TI  - Are waterpipe users tobacco-dependent?

PMID- 24118757
TI  - The importance of addressing waterpipe tobacco smoking: research and policy
      responses.

PMID- 24118758
TI  - Vested interests in addiction research and policy. Is the alcohol industry
      delaying government action on alcohol health warning labels in Australia?
AB  - AIMS: This paper examines the strategies and arguments used by segments of the
      alcohol industry to delay the introduction of mandatory health warning labels on
      alcohol containers in Australia. These strategies are compared with those used by
      the tobacco industry to delay the introduction of warning labels for cigarettes.
      METHODS: Submissions made by members of the alcohol industry to the Australian
      Government's review of labelling and Parliamentary Inquiry into Fetal Alcohol
      Spectrum Disorders were analysed. RESULTS: Segments of the alcohol industry have
      delayed the introduction of mandatory alcohol health warning labels in Australia
      by questioning the rationale and evidence base for labels; arguing that they will
      cause damage to public health and the economy; lobbying and seeking to influence
      government and political representatives including through monetary donations;
      and introducing its own voluntary labelling scheme. The arguments made by these
      organizations against the introduction of mandatory health warning labels for
      alcohol are flawed and their empirical basis is limited. CONCLUSION: The
      Australian Government has delayed the introduction of mandatory alcohol health
      warning labels in Australia by 2 years, until at least December 2013. The
      campaigning of some parts of the alcohol industry appears to have been
      instrumental in this decision.

PMID- 24118759
TI  - Commentary on Dissing et al. (2013): How should we understand the links between
      alcohol consumption and health?

PMID- 24118760
TI  - Commentary on Brooner et al. (2013): one-stop shopping--what sells and what
      doesn't.

PMID- 24118763
TI  - Intra-arterial treatment for massive subcutaneous hemorrhage in hemodialysis
      patients.
AB  - The incidence of acute massive hemorrhage in hemodialysis (HD) patients is
      thought to be higher than in healthy individuals, and a large, expanding
      subcutaneous hematoma can result in necrosis of the overlying skin. We evaluated
      the efficacy of intra-arterial treatment for acute massive subcutaneous
      hemorrhage in HD patients. Seven HD patients with subcutaneous hemorrhage
      following minor blunt trauma were treated using superselective transarterial
      embolization, between July 2005 and October 2012. After examining the site of the
      hemorrhage using contrast-enhanced computed tomography (CT), embolizations were
      performed using microcoils, gelatin sponges, or N-butyl cyanoacrylate. Hematoma
      evacuation or skin grafting was performed as needed. Four men and three women
      with a mean age of 70 years (range, 63-82 years) comprised the study population.
      Sites of bleeding were as follows: lower leg (N = 3), upper leg (N = 1), buttock
      (N = 1), precordia (N = 1), and forearm (N = 1). Blood transfusions were
      administered to five cases. All patients were successfully salvaged using
      transarterial embolization. Six patients underwent hematoma evacuation after
      transarterial embolization, and two patients underwent split-thickness skin
      grafting for skin necrosis. We established a treatment strategy for HD patients
      with acute subcutaneous hemorrhage. Immediate confirmation of the site and the
      degree of bleeding with contrast-enhanced CT and early treatment using the
      transarterial embolization and as needed, hematoma evacuation are effective for
      preventing skin necrosis in HD patients with acute subcutaneous hemorrhage. 

PMID- 24118764
TI  - Domain-specific development of face memory but not face perception.
AB  - How does the remarkable human ability for face recognition arise over
      development? Competing theories have proposed either late maturity (beyond 10
      years) or early maturity (before 5 years), but have not distinguished between
      perceptual and memory aspects of face recognition. Here, we demonstrate a
      perception-memory dissociation. We compare rate of development for (adult, human)
      faces versus other social stimuli (bodies), other discrete objects (cars), and
      other categories processed in discrete brain regions (scenes, bodies), from 5
      years to adulthood. For perceptual discrimination, performance improved with age
      at the same rate for faces and all other categories, indicating no domain
      specific development. In contrast, face memory increased more strongly than non
      face memory, indicating domain-specific development. The results imply that each
      theory is partly true: the late maturity theory holds for face memory, and the
      early maturity theory for face perception. 

PMID- 24118765
TI  - Distinct dissolved organic matter sources induce rapid transcriptional responses
      in coexisting populations of Prochlorococcus, Pelagibacter and the OM60 clade.
AB  - A considerable fraction of the Earth's organic carbon exists in dissolved form in
      seawater. To investigate the roles of planktonic marine microbes in the
      biogeochemical cycling of this dissolved organic matter (DOM), we performed
      controlled seawater incubation experiments and followed the responses of an
      oligotrophic surface water microbial assemblage to perturbations with DOM derived
      from an axenic culture of Prochlorococcus, or high-molecular weight DOM
      concentrated from nearby surface waters. The rapid transcriptional responses of
      both Prochlorococcus and Pelagibacter populations suggested the utilization of
      organic nitrogen compounds common to both DOM treatments. Along with these
      responses, both populations demonstrated decreases in gene transcripts associated
      with nitrogen stress, including those involved in ammonium acquisition. In
      contrast, responses from low abundance organisms of the NOR5/OM60
      gammaproteobacteria were observed later in the experiment, and included elevated
      levels of gene transcripts associated with polysaccharide uptake and oxidation.
      In total, these results suggest that numerically dominant oligotrophic microbes
      rapidly acquire nitrogen from commonly available organic sources, and also point
      to an important role for carbohydrates found within the DOM pool for sustaining
      the less abundant microorganisms in these oligotrophic systems. 

PMID- 24118766
TI  - Improving survival and efficacy of pluripotent stem cell-derived cardiac grafts.
AB  - Human embryonic stem cells (hESCs) can be differentiated into structurally and
      electrically functional myocardial tissue and have the potential to regenerate
      large regions of infarcted myocardium. One of the key challenges that needs to be
      addressed towards full-scale clinical application of hESCs is enhancing survival
      of the transplanted cells within ischaemic or scarred, avascular host tissue.
      Shortly after transplantation, most hESCs are lost as a result of multiple
      mechanical, cellular and host factors, and a large proportion of the remaining
      cells undergo apoptosis or necrosis shortly thereafter, as a result of loss of
      adhesion-related signals, ischaemia, inflammation or immunological rejection.
      Blocking the apoptotic signalling pathways of the cells, using pro-survival
      cocktails, conditioning hESCs prior to transplant, promoting angiogenesis,
      immunosuppressing the host and using of bioengineered matrices are among the
      emerging techniques that have been shown to optimize cell survival. This review
      presents an overview of the current strategies for optimizing cell and host
      tissue to improve the survival and efficacy of cardiac cells derived from
      pluripotent stem cells. 

PMID- 24118767
TI  - Alcohol and breastfeeding.
AB  - While the harmful effects of alcohol during pregnancy are well-established, the
      consequences of alcohol intake during lactation have been far less examined. We
      reviewed available data on the prevalence of alcohol intake during lactation, the
      influence of alcohol on breastfeeding, the pharmacokinetics of alcohol in
      lactating women and nursing infants and the effects of alcohol intake on nursing
      infants. A systematic search was performed in PubMed from origin to May 2013, and
      41 publications were included in the review. Approximately half of all lactating
      women in Western countries consume alcohol while breastfeeding. Alcohol intake
      inhibits the milk ejection reflex, causing a temporary decrease in milk yield.
      The alcohol concentrations in breast milk closely resemble those in maternal
      blood. The amount of alcohol presented to nursing infants through breast milk is
      approximately 5-6% of the weight-adjusted maternal dose, and even in a
      theoretical case of binge drinking, the children would not be subjected to
      clinically relevant amounts of alcohol. Newborns metabolize alcohol at
      approximately half the rate of adults. Minute behavioural changes in infants
      exposed to alcohol-containing milk have been reported, but the literature is
      contradictory. Any long-term consequences for the children of alcohol-abusing
      mothers are yet unknown, but occasional drinking while breastfeeding has not been
      convincingly shown to adversely affect nursing infants. In conclusion, special
      recommendations aimed at lactating women are not warranted. Instead, lactating
      women should simply follow standard recommendations on alcohol consumption. 

PMID- 24118769
TI  - The adrenergic regulation of proximal tubular Na+/H+ exchanger 3 in the rat.
AB  - AIM: This study in the anaesthetized rat investigated how renal sympathetic nerve
      activity and catecholamine release influenced NHE3 abundance and activity in
      proximal tubular brush border membranes using both in vivo and in vitro
      approaches. METHODS: Renal excretory function and brush border NHE3 abundance and
      activity were measured in rat kidneys which underwent renal denervation, renal
      nerve electrical stimulation and renal infusion of phenylephrine and the NHE3
      inhibitor S1661. NHE3 activity and cell surface abundance were also measured in
      primary cultures of proximal tubular cells treated with noradrenaline and
      prazosin. RESULTS: Acute renal denervation caused a natriuresis and diuresis,
      which occurred with a reduction in NHE3 abundance and activity in the brush
      border membranes. By contrast, low-level electrical stimulation of the renal
      innervation causing an antinatriuresis and antidiuresis increased NHE3 activity
      in the brush border membranes. Intrarenal infusion of phenylephrine caused an
      antinatriuresis and antidiuresis, while blockade of NHE3 activity, using local
      infusion of the blocker S1661, caused a natriuresis and diuresis. Exposure of
      primary cultures of proximal tubular cells to noradrenaline increased brush
      border NHE3 abundance and activity which was blocked by prior exposure to
      prazosin, indicating it as an alpha1 -adrenoceptor-mediated mechanism.
      CONCLUSION: Together, these findings demonstrate that the renal sympathetic
      nerves not only have a direct action to modulate tubular sodium reabsorption via
      stimulation of the NHE transporter, but also have an indirect effect, whereby
      NHE3 abundance is increased within the brush border membrane, thereby increasing
      the capacity for fluid reabsorption.

PMID- 24118768
TI  - Architecture and host interface of environmental chlamydiae revealed by electron
      cryotomography.
AB  - Chlamydiae comprise important pathogenic and symbiotic bacteria that alternate
      between morphologically and physiologically different life stages during their
      developmental cycle. Using electron cryotomography, we characterize the
      ultrastructure of the developmental stages of three environmental chlamydiae:
      Parachlamydia acanthamoebae, Protochlamydia amoebophila and Simkania negevensis.
      We show that chemical fixation and dehydration alter the cell shape of
      Parachlamydia and that the crescent body is not a developmental stage, but an
      artefact of conventional electron microscopy. We further reveal type III
      secretion systems of environmental chlamydiae at macromolecular resolution and
      find support for a chlamydial needle-tip protein. Imaging bacteria inside their
      host cells by cryotomography for the first time, we observe marked differences in
      inclusion morphology and development as well as host organelle recruitment
      between the three chlamydial organisms, with Simkania inclusions being tightly
      enveloped by the host endoplasmic reticulum. The study demonstrates the power of
      electron cryotomography to reveal structural details of bacteria-host
      interactions that are not accessible using traditional methods. 

PMID- 24118770
TI  - Sugar homeostasis mediated by cell wall invertase GRAIN INCOMPLETE FILLING 1
      (GIF1) plays a role in pre-existing and induced defence in rice.
AB  - Sugar metabolism and sugar signalling are not only critical for plant growth and
      development, but are also important for stress responses. However, how sugar
      homeostasis is involved in plant defence against pathogen attack in the model
      crop rice remains largely unknown. In this study, we observed that the grains of
      gif1, a loss-of-function mutant of the cell wall invertase gene GRAIN INCOMPLETE
      FILLING 1 (GIF1), were hypersusceptible to postharvest fungal pathogens, with
      decreased levels of sugars and a thinner glume cell wall in comparison with the
      wild-type. Interestingly, constitutive expression of GIF1 enhanced resistance to
      both the rice bacterial pathogen Xanthomonas oryzae pv. oryzae and the fungal
      pathogen Magnaporthe oryzae. The GIF1-overexpressing (GIF1-OE) plants accumulated
      higher levels of glucose, fructose and sucrose compared with the wild-type
      plants. More importantly, higher levels of callose were deposited in GIF1-OE
      plants during pathogen infection. Moreover, the cell wall was much thicker in the
      infection sites of the GIF1-OE plants when compared with the wild-type plants. We
      also found that defence-related genes were constitutively activated in the GIF1
      OE plants. Taken together, our study reveals that sugar homeostasis mediated by
      GIF1 plays an important role in constitutive and induced physical and chemical
      defence.

PMID- 24118771
TI  - Faculty of Radiation Oncology 2012 trainee survey: perspectives on choice of
      specialty training and future work practice preferences.
AB  - INTRODUCTION: This paper reports the key findings of the first Faculty of
      Radiation Oncology survey of trainees dealing with experiences and perceptions on
      work practices and choice of specialty. METHODS: The survey was conducted in mid
      2012 using a 37-question instrument. This was distributed by email to 159 current
      trainees and advertised through the Radiation Oncology Trainees Committee and
      other channels. There were six email reminders. Respondents were reassured that
      their responses were anonymous. RESULTS: The overall response rate was 82.8%.
      Gender was balanced among respondents with 67 (51.5%) being male and 63 (48.5%)
      being female. The most common age bracket was the 31 to 35 years range. There
      were similar proportions of trainee responders in each of the five years of
      training. A substantial number of trainees held other degrees besides medical
      degrees. The large majority were satisfied with radiation oncology as a career
      choice and with the Training Network within which they were training. Interest in
      oncology patients, lifestyle after training and work hours were given as the
      major reasons for choosing radiation oncology as a career. Nearly half of
      trainees were interested in undertaking some of their training in a part-time
      capacity and working part time as a radiation oncologist in the future. Over 70%
      of trainees stated they were working 36-55 clinical hours per week with
      additional non-clinical tasks, after-hours work and on-call duties. Nearly half
      of all trainees reported having one or less hours of protected time per week.
      Nonetheless, 40% of respondents indicated they had enough time to pursue outside
      interests. Radiation treatment planning and maintaining currency in general
      medicine were considered the most difficult aspects of training in radiation
      oncology. Most respondents were keen on the concept of fostering a research
      mentor. In terms of views on practice after completion of training, the majority
      were interested in pursuing a fellowship, and nearly all expressed an interest in
      maintaining an element of academic practice. The large majority of respondents
      preferred to work in an urban department as a component of their practice after
      training and nearly all wanted a component of public sector practice. There were
      only four per cent who preferred to work only within the private sector. Job
      availability was a concern for 94% of trainees, which far outweighed any other
      concerns. CONCLUSIONS: Trainees in radiation oncology are generally satisfied
      with their choice of specialty and their training. Most trainees are interested
      in fellowship positions, links with academia and largely public sector work in
      the future. Job availability for the future is their major concern.

PMID- 24118772
TI  - Biosimilars: how similar?
AB  - As patents expire on biological agents for the treatment of rheumatic diseases,
      we have the opportunity to develop non-proprietary biologic agents, biosimilars.
      The development and approval of these agents present novel challenges to both
      pharma and regulatory agencies although there is great promise of high quality,
      less expensive biologic agents for the treatment of rheumatic diseases. Here, we
      review the definitions of biosimilars, the regulatory challenges to approval of
      these agents and the record of approvals of biosimilars to date. 

PMID- 24118773
TI  - Development of an Australian version of the Alcohol-Related Problems Survey: a
      comprehensive computerised screening tool for older adults.
AB  - AIM: The Alcohol-Related Problems Survey (ARPS) reliably classifies drinking as
      non-hazardous, hazardous or harmful using scoring algorithms that consider
      quantity and frequency of alcohol use alone and in combination with health
      conditions, medication-use and functional status. Because it has been developed
      using a 14-g US standard drink, it is not valid in Australia where a standard
      drink contains 10 g of ethanol. METHOD: We recalibrated the ARPS scoring
      algorithms for a 10-g Australian standard drink and updated the list of
      medications. The Australian ARPS (A-ARPS) was then administered to 50 non
      treatment-seeking participants in waves of five. RESULTS: The A-ARPS recalibrated
      scoring algorithms reliably classified all 50 individuals. Sixty-six per cent
      were classified as hazardous or harmful drinkers. Many were taking medications
      that interact with alcohol or had medical conditions that can be exacerbated by
      alcohol consumption. CONCLUSION: The A-ARPS is available for use in Australia.
      Its utilisation could reduce the incidence of alcohol-related harms.

PMID- 24118774
TI  - Intrathecal drug administration in chronic pain syndromes.
AB  - Chronic pain may recur after initial response to strong opioids in both patients
      with cancer and patients without cancer or therapy may be complicated by
      intolerable side effects. When minimally invasive interventional pain management
      techniques also fail to provide satisfactory pain relief, continuous intrathecal
      analgesic administration may be considered. Only 3 products have been officially
      approved for long-term intrathecal administration: morphine, baclofen, and
      ziconotide. The efficacy of intrathecal ziconotide for the management of patients
      with severe chronic refractory noncancer pain was illustrated in 3 placebo
      controlled trials. A randomized study showed this treatment option to be
      effective over a short follow-up period for patients with pain due to cancer or
      AIDS. The efficacy of intrathecal opioid administration for the management of
      chronic noncancer pain is mainly derived from prospective and retrospective
      noncontrolled trials. The effect of intrathecal morphine administration in
      patients with pain due to cancer was compared with oral or transdermal treatment
      in a randomized controlled trial, which found better pain control and fewer side
      effects with intrathecal opioids. Other evidence is derived from cohort studies.
      Side effects of chronic intrathecal therapy may either be technical (catheter or
      pump malfunction) or biological (infection). The most troublesome complication
      is, however, the possibility of granuloma formation at the catheter tip that may
      induce neurological damage. Given limited studies, the evidence for intrathecal
      drug administration in patients suffering from cancer-related pain is more
      compelling than that of chronic noncancer pain. 

PMID- 24118775
TI  - Effects of intravenous and intrathecal dexmedetomidine in spinal anesthesia: a
      meta-analysis.
AB  - PURPOSE: To assess the effects of dexmedetomidine on the duration of sensory and
      motor block, postoperative analgesia, hypotension, bradycardia, and side effects
      in patients undergoing spinal anesthesia. METHODS: Two researchers searched
      MEDLINE, EMBASE, and the Cochrane controlled trial register independently for
      randomized controlled trials comparing dexmedetomidine with a placebo without any
      language restrictions. RESULTS: A total of 412 patients from eight trials were
      included in this study. The results revealed that dexmedetomidine was
      statistically significant in prolonging the duration of sensory block (mean
      difference, MD = 73.55; 95% CI, [55.69, 91.40] P < 0.00001, I(2)  = 89%) and
      motor block (MD = 59.11; 95% CI, [29.58, 88.65] P < 0.00001, I(2)  = 91%) and the
      time to first request for postoperative analgesia (MD = 245.77, 95% CI, [143.53,
      348.00] P < 0.00001, I(2)  = 98%). The occurrence of hypotension (OR = 0.60, 95%
      CI, [0.3-1.23], P = 0.40, I(2)  = 3%) and side effects (OR = 0.9, 95% CI, [0.36
      2.22], P = 0.88, I(2)  = 0%) was not significantly different between
      dexmedetomidine and placebo. However, dexmedetomidine was associated with more
      frequent bradycardia requiring atropine (OR = 7.55; 95% CI, [2.76-20.63], P =
      0.63, I(2)  = 0%). CONCLUSIONS: This meta-analysis has shown that dexmedetomidine
      prolonged the duration of spinal anesthesia and improved postoperative analgesia
      and did not increase the incidence of hypotension and adverse events, but needs
      more atropine to reverse bradycardia.

PMID- 24118776
TI  - What is the evidence that neuropathic pain is present in chronic low back pain
      and soft tissue syndromes? An evidence-based structured review.
AB  - OBJECTIVES: The objectives of this evidence-based review were to review the
      evidence for whether neuropathic pain (NP) is associated with chronic low back
      pain (CLBP) and soft tissue syndromes (STS), and review the reported prevalence
      percentages for NP within these syndromes. METHODS: Of 816 reports, 11 addressed
      the diagnosis of NP in CLBP and five of NP in STS. Studies were grouped by the
      method of arrival at an NP diagnosis, e.g., physical examination, type of NP
      inventory utilized, etc. The reported prevalence of NP was determined by
      aggregating all the patients in all the studies in each grouping. Similarly, the
      reported prevalence of NP within CLBP and STS was determined by aggregating all
      the patients with NP from all the studies in those groups. Each study was
      independently rated by two raters according to 11 quality criteria generating a
      quality score. The strength and consistency (SAC) of the evidence represented by
      each grouping was rated according to Agency for Health Care Policy and Research
      guidelines. RESULTS: In each grouping, 100% of the studies reported some
      prevalence of NP (none reported zero prevalence). Aggregated NP prevalence for
      CLBP was 36.6% (SAC level A [consistent multiple studies]) and for STS 41.1% (SAC
      level A). There was significant variation in prevalence according to the method
      utilized to diagnose NP. CONCLUSION: There is consistent evidence by all methods
      that NP is present in CLBP and STS. Reported prevalence percentages by all
      methods are substantial. This has significant implications for the treatment of
      CLBP and STS.

PMID- 24118777
TI  - Complementary feeding practices and child growth outcomes in Haiti: an analysis
      of data from Demographic and Health Surveys.
AB  - The Haitian National Nutrition Policy identifies the promotion of optimal
      complementary feeding (CF) practices as a priority action to prevent childhood
      malnutrition. We analysed data from the nationally representative 2005-2006 Haiti
      Demographic Health Survey using the World Health Organization 2008 infant and
      young child feeding indicators to describe feeding practices among children aged
      6-23 months and thus inform policy and programme planning. Multivariate
      regression analyses were used to identify the determinants of CF practices and to
      examine their association with child growth outcomes. Overall, 87.3% of 6-8-month
      olds received soft, solid or semi-solid foods in the previous 24 h. Minimum
      dietary diversity (MDD), minimum meal frequency (MMF) and minimum acceptable diet
      (MAD) were achieved in 29.2%, 45.3% and 17.1% of children aged 6-23 months,
      respectively. Non-breastfed children were more likely to achieve MDD than
      breastfed children of the same age (37.3% vs. 25.8%; P < 0.001). The proportion
      of children achieving MMF varied significantly by age (P < 0.001). Children with
      overweight mothers were more likely to achieve MDD, MMF and MAD [odds ratio (OR)
      2.08, P = 0.012; OR 1.81, P = 0.02; and OR 2.4, P = 0.01, respectively] than
      children of normal weight mothers. Odds of achieving MDD and MMF increased with
      household wealth. Among mothers with secondary or more education, achieving MDD
      or MAD was significantly associated with lower mean weight-for-age z-score and
      height-for-age z-score (P-value <0.05 for infants and young child feeding
      indicator * maternal education interaction). CF practices were mostly inadequate
      and contributed to growth faltering among Haitian children 6-23 months old. 

PMID- 24118778
TI  - Association of a potential functional pre-miR-218 polymorphism and its
      interaction with hepatitis B virus mutations with hepatocellular carcinoma risk.
AB  - BACKGROUND & AIMS: MicroRNA-218 (miR-218) can function as a tumour suppressor and
      inactivate cancer-promoting inflammation. However, role of miR-218 on
      hepatocellular carcinoma (HCC) remains unclear. To determine the contribution of
      miR-218 genetic predisposition and its interaction with hepatitis B virus (HBV)
      mutations to HCC risk. METHODS: rs11134527 located at putative promoter region of
      pre-miR-218 was genotyped in 1012 healthy controls, 302 hepatitis B surface
      antigen (HBsAg) seroclearance subjects and 2011 subjects with chronic HBV
      infection (1021 with HCC) using quantitative PCR. HBV mutation was determined by
      sequencing. RESULTS: rs11134527 variant genotypes in dominant model was
      associated with HCC risk compared with all HCC-free subjects [odds ratio (OR) =
      1.22, 95% confidence interval (CI) = 1.04-1.43], HCC-free HBsAg-positive subjects
      (OR = 1.23, 95% CI = 1.02-1.50) and HBsAg seroclearance subjects (OR = 1.45, 95%
      CI = 1.08-1.96), adjusting for age and gender, and also associated with the
      generation of HBV preS deletion in men (adjusted OR = 1.85, 95% CI = 1.23-2.76).
      In multivariate regression analyses, rs11134527 in dominant model was associated
      with HCC risk (OR = 1.50, 95% CI = 1.05-2.13), whereas its multiplicative
      interaction with viral mutation T1674C/G was inversely associated with HCC risk
      (OR = 0.44, 95% CI = 0.21-0.96), adjusting for covariates including HBV mutations
      in the enhancer II-precore region; its interaction with HBV preS1 start codon
      mutation was associated with HCC risk (OR = 4.44, 95% CI = 1.27-15.55), adjusting
      for covariates including HBV mutations in the preS region. CONCLUSION: rs11134527
      may be a novel genetic risk factor of HCC in HBV-exposed subjects, can facilitate
      HBV preS deletion generation and predispose the host to the effect of T1674C/G
      and preS1 start codon mutation in hepatocarcinogenesis.

PMID- 24118779
TI  - Vertical partitioning of nitrogen-loss processes across the oxic-anoxic interface
      of an oceanic oxygen minimum zone.
AB  - We investigated anammox, denitrification and dissimilatory reduction of nitrite
      to ammonium (DNRA) activity in the Eastern Tropical South Pacific oxygen minimum
      zone (OMZ) off northern Chile, at high-depth resolution through the oxycline into
      the anoxic OMZ core. This was accompanied by high-resolution nutrient and oxygen
      profiles to link changes in nitrogen transformation rates to physicochemical
      characteristics of the water column. Denitrification was detected at most depths,
      but anammox was the most active N2 -producing process, while DNRA was not
      detectable. Anammox and denitrification were mainly active in the anoxic OMZ core
      while activity was low to not detectable in the oxycline, except in association
      with an intrusion of OMZ core water. This indicates that continuous exposure to
      even submicromolar oxygen levels inhibits the processes either directly or
      through nitrite limitation. Anammox activity did not peak at the oxic-anoxic
      boundary but 20-50 m below matching the salinity maximum of the Equatorial
      Subsurface Water. This suggests that water history plays a major role for anammox
      activity possibly due to slow growth of anammox bacteria. Denitrification peaked
      deeper than anammox, likely reflecting a shift in the balance between this
      process and nitrate reduction to nitrite, governed by the relative availability
      of nitrate and nitrite.

PMID- 24118780
TI  - Distichiasis in a ferret (Mustela putorius furo).
AB  - A 4-year-old intact male ferret was presented to the Ophthalmology Service of the
      Department of Clinical Sciences of Companion Animals of Utrecht University with
      chronic blepharospasm, epiphora, and conjunctivitis of the right eye. Examination
      of the eye revealed mild conjunctivitis and three hairs protruding from the
      openings of meibomian glands in the upper eyelid, providing the clinical
      diagnosis of distichiasis. The distichia were removed by transconjunctival
      unipolar electrocautery. Recovery was uneventful, but the original signs recurred
      10 weeks after surgery. Ophthalmic examination revealed another distichia at a
      different location in the same eyelid and it was removed by full-thickness wedge
      excision. Histopathological examination failed to reveal the exact origin of the
      distichia. To our knowledge, this is the first reported case of distichiasis in a
      ferret.

PMID- 24118781
TI  - Clinicopathologic features of post-transplant lymphoproliferative disorders
      arising after pediatric small bowel transplant.
AB  - Few studies examined the clinicopathologic features of PTLD arising in pediatric
      SBT patients. Particularly, the association between ATG and PTLD in this
      population has not been described. Retrospective review of 81 pediatric patient
      charts with SBT--isolated or in combination with other organs--showed a PTLD
      incidence of 11%, occurring more frequently in females (median age of four yr)
      and with clinically advanced disease. Monomorphic PTLD was the most common
      histological subtype. There was a significant difference in the use of ATG
      between patients who developed PTLD and those who did not (p < 0.01); a similar
      difference was seen with the use of sirolimus (p < 0.001). These results
      suggested a link between the combination of ATG and sirolimus and development of
      more clinically and histologically advanced PTLD; however, the risk of ATG by
      itself was not clear. EBV viral loads were higher in patients with PTLD, and
      median time between detection of EBV to PTLD diagnosis was three months. However,
      viral loads at the time of PTLD diagnosis were most often lower than at EBV
      detection, thereby raising questions on the correlation between decreasing viral
      genomes and risk of PTLD.

PMID- 24118782
TI  - Topical application of recombinant platelet-derived growth factor increases the
      rate of healing and the level of proteins that regulate this response.
AB  - A bipedicle ischaemic rat skin flap model was used to study the effects of daily
      topical applications of platelet-derived growth factor (PDGF) on the healing of
      ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1
      beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2
      (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of
      72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and
      ischaemic wounds received either vehicle or 0.01% recombinant PDGF-BB. Additional
      applications were made on the wounds on a daily basis. Wound areas were measured
      at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound
      healing as well as an increase in TNFA, IL1B and both the pro and active forms of
      MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and
      ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA
      concentration in both normal and ischaemic wounds, and the rate of wound healing
      closely resembled the pattern of TNFA protein expression. PDGF also reduced both
      the magnitude and duration of the increases in IL1B and both the pro and active
      forms of MMP2 and MMP9 induced by ischaemia. 

PMID- 24118783
TI  - Obesity paradox in people newly diagnosed with type 2 diabetes with and without
      prior cardiovascular disease.
AB  - AIM: To address the debate on 'obesity paradox' in patients with type 2 diabetes
      mellitus (T2DM) by evaluating the cardiovascular and mortality risks associated
      with normal and overweight patients compared to obese at diagnosis of diabetes,
      separately for patients with and without cardiovascular disease (CVD) before
      diagnosis. METHODS: A retrospective study with two study cohorts with/without
      prior CVD (n = 10237/37272) with complete measures of body mass index (BMI) at
      diagnosis of T2DM from UK General Practice Research Database. Primary outcomes
      were long-term risks of cardiovascular events (CVEs) and all-cause mortality in
      patients with normal weight, overweight and obesity at diagnosis. RESULTS: The
      mortality rates per 1000 person-years in normal weight, overweight and obese
      patients among patients without prior CVD were 13.1, 8.6 and 6.0, respectively,
      during 5 years of median follow-up. For patients with prior CVD, these estimates
      were 30.1, 21.1 and 15.5, respectively. Among patients without and with prior
      CVD, normal weight patients had 47% (hazard ratio, HR CI: 1.29, 1.69) and 30% (HR
      CI: 1.11, 1.53) increased mortality risk respectively compared to obese patients.
      In the cohort without prior CVD, compared to obese patients, those with normal
      body weight did not have increased CVE risk. Interactions between age, HbA1c and
      BMI at diagnosis were observed in both cohorts. CONCLUSIONS: Adults with normal
      weight at the diagnosis of T2DM have significantly higher mortality risk compared
      to those who are obese, with significant interactions between age, BMI and HbA1c.
      Elevated cardiovascular risk was not observed in normal weight patients without
      prior CVD.

PMID- 24118784
TI  - Effect of antioxidant vitamin supplementation on endothelial function in type 2
      diabetes mellitus: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - Controversy exists among trials assessing whether prolonged antioxidant vitamin
      supplementation improves endothelial function in type 2 diabetes mellitus (T2DM)
      subjects. The aim of this study was to systematically review and quantify the
      effect of antioxidant vitamin supplementation on endothelial function in T2DM
      subjects. MEDLINE, Cochrane, Scopus and Web of Science were searched up to
      February 2013 for randomized controlled trials assessing the effect of
      antioxidant vitamin E and/or C supplementation on endothelial function in T2DM
      subjects. Ten randomized controlled trials comparing antioxidant vitamin
      supplemented and control groups (overall n = 296) met the inclusion criteria.
      Post-intervention standardized mean difference (SMD) in endothelial function did
      not reach statistical significance between groups (0.35; 95% confidence interval
      = -0.17, 0.88; P = 0.18). In subgroup analysis, post-intervention endothelial
      function was significantly improved by antioxidant vitamin supplementation in
      T2DM subgroups with body mass index (BMI) <= 29.45 kg m(-2) (SMD = 1.02; P <
      0.05), but not in T2DM subgroups with BMI > 29.45 kg m(-2) (SMD = -0.07; P =
      0.70). In meta-regression, an inverse association was found between BMI and post
      intervention SMD in endothelial function (B = -0.024, P = 0.02). Prolonged
      antioxidant vitamin E and/or C supplementation could be effective to improve
      endothelial function in non-obese T2DM subjects.

PMID- 24118785
TI  - Challenges for Serology-Based Characterization of Foot-and-Mouth Disease
      Outbreaks in Endemic Areas; Identification of Two Separate Lineages of Serotype O
      FMDV in Uganda in 2011.
AB  - Control of foot-and-mouth disease (FMD) in Uganda by ring vaccination largely
      depends on costly trivalent vaccines, and use of monovalent vaccines could
      improve the cost effectiveness. This, however, requires application of highly
      specific diagnostic tests. This study investigated outbreaks of FMD in seven
      Ugandan districts, during 2011, using the PrioCHECK(r) FMDV NS ELISA, solid-phase
      blocking ELISAs (SPBEs) and virus neutralization tests (VNTs), together with
      virological analyses for characterization of the responsible viruses. Two hundred
      and eighteen (218) cattle and 23 goat sera as well as 82 oropharyngeal
      fluid/epithelial tissue samples were collected. Some 50% of the cattle and 17% of
      the goat sera were positive by the PrioCHECK(r) FMDV NS ELISA, while SPBEs
      identified titres >=80 for antibodies against serotype O FMD virus (FMDV) in 51%
      of the anti-NSP positive cattle sera. However, 35% of the anti-NSP positive
      cattle sera had SPBE titres >=80 against multiple serotypes, primarily against
      serotypes O, SAT 1 and SAT 3. Comparison of SPBEs and VNTs for the detection of
      antibodies against serotypes O, SAT 1 and SAT 3 in 72 NSP positive cattle sera
      showed comparable results against serotype O (P = 0.181), while VNTs detected
      significantly fewer samples positive for antibodies against SAT 1 and SAT 3 than
      the SPBEs (P < 0.001). Detection of antibodies against serotype O was consistent
      with the isolation of serotype O FMDVs from 13 samples. Four of these viruses
      were sequenced and belonged to two distinct lineages within the East Africa-2 (EA
      2) topotype, each differing from the currently used vaccine strain (EA-1
      topotype). The relationships of these lineages to other serotype O viruses in the
      Eastern Africa region are discussed. To enhance the control of FMD in Uganda,
      there is need to improve the specificity of the SAT-SPBEs, perform vaccine
      matching and implement improved regional FMD control.

PMID- 24118786
TI  - Role of pre-junctional CB1, but not CB2 , TRPV1 or GPR55 receptors in anandamide
      induced inhibition of the vasodepressor sensory CGRPergic outflow in pithed rats.
AB  - Stimulation of the perivascular sensory outflow in pithed rats produces
      vasodepressor responses mediated by CGRP release. Interestingly, endocannabinoids
      such as anandamide (which interacts with CB1 , CB2 , TRPV1 and GPR55 receptors)
      can regulate the activity of perivascular sensory nerves in dural blood vessels
      by modulating CGRP release. Yet, as no publication has reported whether this
      mechanism is operative in the healthy systemic vasculature, this study has
      specifically analysed the receptors mediating the potential inhibitory effects of
      the cannabinoid (CB) receptor agonists anandamide (non-selective), JWH-015 (CB2 )
      and lysophosphatidylinositol (GPR55) on the rat vasodepressor sensory CGRPergic
      outflow (an index of systemic vasodilatation). Healthy pithed rats were pre
      treated with consecutive i.v. continuous infusions of hexamethonium, methoxamine
      and the above agonists. Electrical spinal (T9 -T12 ) stimulation of the
      vasodepressor sensory CGRPergic outflow or i.v. injections of alpha-CGRP produced
      frequency-dependent or dose-dependent vasodepressor responses. The infusions of
      anandamide in a dose-dependent manner inhibited the vasodepressor responses by
      electrical stimulation (remaining unaffected by JWH-015 or
      lysophosphatidylinositol), but not those by alpha-CGRP. After i.v. administration
      of antagonists, the inhibition by 3.1 MUg/kg min anandamide was: (i) potently
      blocked by 31-100 MUg/kg NIDA41020 (CB1 ), (ii) unaffected by 180 MUg/kg AM630
      (CB2 ), 31 MUg/kg cannabidiol (GPR55) or 31-100 MUg/kg capsazepine (TRPV1) and
      (iii) slightly blocked by 310 MUg/kg AM630. The above doses of antagonists were
      enough to block their respective receptors. These results suggest that anandamide
      induced inhibition of the vasodepressor sensory CGRPergic outflow is mainly
      mediated by pre-junctional activation of CB1 receptors, with no pharmacological
      evidence for the role of CB2 , TRPV1 or GPR55 receptors.

PMID- 24118787
TI  - Influences of vowel and tone variation on emergent word knowledge: a cross
      linguistic investigation.
AB  - To learn words, infants must be sensitive to native phonological contrast. While
      lexical tone predominates as a source of phonemic contrast in human languages,
      there has been little investigation of the influences of lexical tone on word
      learning. The present study investigates infants' sensitivity to tone
      mispronunciations in two groups of infants. For one group (Chinese learners),
      tone is phonemic in their native language, and for the second group (English
      learners), tone is non-phonemic and constituted suprasegmental variation. In
      Experiment 1, English learners were trained on novel word-object pairings and
      tested on their recognition of correct pronunciations, tone and vowel
      mispronunciations of these words at 18 and 24 months. In Experiment 2a, bilingual
      English-Chinese learners were tested on a similar task translated into Chinese at
      the same age intervals. Results demonstrate that non-tonal learners treated tonal
      and vowel substitutions alike as mispronunciations at 18 months but only treated
      vowel substitutions as mispronunciations at 24 months. Tonal learners treated
      both tonal and vowel substitutions as mispronunciations at both ages. In
      Experiment 2b, bilingual non-tone language learners were tested on the same set
      of tasks replicating a similar set of results as monolingual non-tone language
      learners (Experiment 1). Findings point to an early predisposition to treat tone
      as a defining characteristic of words regardless of its lexical relevance at 18
      months. Between 18 and 24 months, learners appear to ascribe lexical relevance to
      tone in a language-specific manner. The current study identifies the influences
      of tone variation on memories for newly learned words and the time period during
      which lexical tone - a highly frequent constituent of human languages - actually
      becomes lexical for early learners. Findings are contextualized with prevailing
      models of the developing lexicon. 

PMID- 24118788
TI  - Genetic variation in interleukin 28B and correlation with chronic hepatitis B
      virus infection in Saudi Arabian patients.
AB  - BACKGROUND & AIMS: Several genome-wide association studies have shown that
      genetic variations in the chromosomal region containing interleukin-28B (IL28B)
      gene are associated with response to treatment in hepatitis C virus (HCV)
      infection. This study was conducted to examine the role of genetic variations in
      IL28B on disease progression in Saudi Arabian patients chronically infected with
      hepatitis B virus (HBV). METHODS: The study included 1128 subjects divided into
      four categories; 304 clearance subjects, 518 inactive carriers, 212 active
      carriers and 94 cirrhosis/HCC. RESULTS: Three single nucleotide polymorphisms
      (SNPs), rs12979860 (OR=1.307; 95% CI 1.046-1.634, chi2=5.57 and P=0.0183),
      rs12980275 (OR=0.642; CI 0.517-0.798, chi2=16.17 and P=0.0001) and rs8105790
      (OR=0.746; CI 0.592-0.941, chi2=6.12 and P=0.0133), were found to be strongly
      associated with HBV clearance. The frequency of the G allele of rs12980275 and
      the C allele of rs8105790 were found to be more in clearance group than in
      patients and could contribute to protection against the disease. On the other
      hand, only rs12979860 showed significant difference in distribution when inactive
      group was compared to other groups (OR=1.285; CI 1.030-1.603, chi2=4.95,
      P=0.0261). No significant association was evident for any of the variants when
      active carriers were compared to cirrhosis/HCC patients. Haplotype analysis
      showed that a combination of A-T-T-G of rs12980275, rs8105790, rs8099917, and
      rs7248668, respectively, was associated with clearance of the virus
      (frequency=67.5% and P=0.015). CONCLUSION: genetic variations in IL28B gene
      region may influence the clearance of HBV infection.

PMID- 24118789
TI  - Consumer involvement in cancer research: example from a Cancer Network.
AB  - BACKGROUND: The involvement of consumers and the general public in improving
      cancer services is an important component of health services. However, consumer
      involvement in cancer research is relatively unexplored. The objective of this
      study was to explore different ways of involving consumers in cancer research in
      one regional network. METHODS: Thames Valley Cancer Network Consumer Research
      Partnership (CRP) group was formed in 2009. The group consists of consumers and
      professionals to help in promoting consumer involvement in Cancer Research in the
      Thames Valley. This study evaluated the project of consumer involvement in cancer
      research in the Thames Valley from March 2010 to March 2011. We used different
      indices to judge the level of consumer involvement: number of projects involving
      consumers through the group, types of projects, level of involvement (ranged from
      consultation on research documents to collaborating in preparing grant
      applications) and the methods of involving consumers in cancer research. RESULTS:
      Fifteen projects were submitted to the CRP group during the 12-month period
      studied. Of these, eight projects were clinical trials, three were qualitative
      research projects, two were patients' surveys and two were non-randomized
      interventional studies. Seven projects requested consumer involvement on patient
      information sheets for clinical trials. Of these seven applications, three also
      requested consumers' help in designing research questionnaires and another three
      requested that consumers should be involved in their project management group. In
      addition, four projects involved consumers in the proposal development phase and
      another four projects asked for advice on how to increase trial recruitment,
      conduct patient interviews or help with grant applications. CONCLUSIONS: The
      creation of the CRP and this audit of its activity have documented consumer
      involvement in cancer research in the Thames Valley. We have clearly shown that
      consumers can be involved in designing and managing cancer research projects.

PMID- 24118790
TI  - Expression of tomato salicylic acid (SA)-responsive pathogenesis-related genes in
      Mi-1-mediated and SA-induced resistance to root-knot nematodes.
AB  - The expression pattern of pathogenesis-related genes PR-1, PR-2 and PR-5,
      considered as markers for salicylic acid (SA)-dependent systemic acquired
      resistance (SAR), was examined in the roots and shoots of tomato plants pre
      treated with SA and subsequently infected with root-knot nematodes (RKNs)
      (Meloidogyne incognita). PR-1 was up-regulated in both roots and shoots of SA
      treated plants, whereas the expression of PR-5 was enhanced only in roots. The
      over-expression of PR-1 in the whole plant occurred as soon as 1 day after SA
      treatment. Up-regulation of the PR-1 gene was considered to be the main marker of
      SAR elicitation. One day after treatment, plants were inoculated with active
      juveniles (J2s) of M. incognita. The number of J2s that entered the roots and
      started to develop was significantly lower in SA-treated than in untreated plants
      at 5 and 15 days after inoculation. The expression pattern of PR-1, PR-2 and PR-5
      was also examined in the roots and shoots of susceptible and Mi-1-carrying
      resistant tomato plants infected by RKNs. Nematode infection produced a down
      regulation of PR genes in both roots and shoots of SA-treated and untreated
      plants, and in roots of Mi-carrying resistant plants. Moreover, in resistant
      infected plants, PR gene expression, in particular PR-1 gene expression, was
      highly induced in shoots. Thus, nematode infection was demonstrated to elicit SAR
      in shoots of resistant plants. The data presented in this study show that the
      repression of host defence SA signalling is associated with the successful
      development of RKNs, and that SA exogenously added as a soil drench is able to
      trigger a SAR-like response to RKNs in tomato. 

PMID- 24118791
TI  - Adipose afferent reflex: sympathetic activation and obesity hypertension.
AB  - Excessive sympathetic activity contributes to the pathogenesis of hypertension
      and the progression of the related organ damage. Adipose afferent reflex (AAR) is
      a sympatho-excitatory reflex that the afferent activity from white adipose tissue
      (WAT) increases sympathetic outflow and blood pressure. Hypothalamic
      paraventricular nucleus (PVN or PVH) is one of the central sites in the control
      of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR.
      The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent
      activity and AAR contribute to the excessive sympathetic activation and
      hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic
      activity and hypertension. Leptin may be one of sensors in the WAT for the AAR,
      and is involved in the enhanced AAR in obesity and hypertension. This review
      focuses on the neuroanatomical basis and physiological functions of the AAR, and
      the important role of the enhanced AAR in the pathogenesis of obesity
      hypertension. 

PMID- 24118793
TI  - General practitioners' knowledge of ageing and attitudes towards older people in
      China.
AB  - AIM: To explore general practitioners (GPs)knowledge of ageing, attitudes towards
      older people and factors affecting their knowledge and attitudes in a Chinese
      context. METHODS: Four hundred GPs were surveyed using the Chinese version of the
      Aging Semantic Differential (CASD) and the Chinese version of the Facts on Aging
      Quiz (CFAQ1) scale. RESULTS: The CASD scores indicated that GPs had a neutral
      attitude towards older people. The CFAQ1 scores indicated a low level of
      knowledge about ageing. GPs' awareness of the mental and social facts of ageing
      was poorer compared to that of physical facts. Male GPs had a significantly
      higher negative bias score than female GPs. No other variables had a
      statistically significant influence on knowledge and attitudes. CONCLUSIONS: The
      findings suggest the need for education interventions for GPs regarding knowledge
      of ageing and also provide evidence to guide future development of continuing
      medical programs for this group of medical doctors.

PMID- 24118792
TI  - Repeated H2 O2 exposure drives cell cycle progression in an in vitro model of
      ulcerative colitis.
AB  - The production of hydrogen peroxide (H2 O2 ) drives tumourigenesis in ulcerative
      colitis (UC). Recently, we showed that H2 O2 activates DNA damage checkpoints in
      human colonic epithelial cells (HCEC) through c-Jun N-terminal Kinases (JNK) that
      induces p21(WAF1) . Moreover, caspases circumvented the G1/S and intra-S
      checkpoints, and cells accumulated in G2/M. The latter observation raised the
      question of whether repeated H2 O2 exposures alter JNK activation, thereby
      promoting a direct passage of cells from G2/M arrest to driven cell cycle
      progression. Here, we report that increased proliferation of repeatedly H2 O2 
      exposed HCEC cells (C-cell cultures) was associated with (i) increased phospho
      p46 JNK, (ii) decreased total JNK and phospho-p54 JNK and (iii) p21(WAF1) down
      regulation. Altered JNK activation and p21(WAF1) down-regulation were accompanied
      by defects in maintaining G2/M and mitotic spindle checkpoints through
      adaptation, as well as by apoptosis resistance following H2 O2 exposure. This may
      cause increased proliferation of C-cell cultures, a defining initiating feature
      in the inflammation-carcinoma pathway in UC. We further suggest that dysregulated
      JNK activation is attributed to a non-apoptotic function of caspases, causing
      checkpoint adaptation in C-cell cultures. Additionally, loss of cell-contact
      inhibition and the overcoming of senescence, hallmarks of cancer, contributed to
      increased proliferation. Furthermore, there was evidence that p54 JNK
      inactivation is responsible for loss of cell-contact inhibition. We present a
      cellular model of UC and suggest a sinusoidal pattern of proliferation, which is
      triggered by H2 O2 -induced reactive oxygen species generation, involving an
      interplay between JNK activation/inactivation, p21(WAF1) , c-Fos, c-Jun/phospho-c
      Jun, ATF2/phospho-ATF2, beta-catenin/TCF4-signalling, c-Myc, CDK6 and Cyclin D2,
      leading to driven cell cycle progression. 

PMID- 24118794
TI  - Association between lowered endothelial function measured by peripheral arterial
      tonometry and cardio-metabolic risk factors - a cross-sectional study of Finnish
      municipal workers at risk of diabetes and cardiovascular disease.
AB  - BACKGROUND: The aim of this cross-sectional study was to determine the
      association between lowered endothelial function measured by peripheral arterial
      tonometry (PAT) and cardio-metabolic risk factors. The study population consisted
      of Finnish municipal workers who were at risk of diabetes or cardiovascular
      disease and who had expressed a need to change their health behaviour. METHODS: A
      total of 312 middle-aged municipal workers underwent a physical medical
      examination and anthropometry measurements. Levels of total cholesterol, HDL
      cholesterol, triglycerides, fasting glucose, glycated haemoglobin, and high
      sensitivity C-reactive protein were taken from the blood samples. PAT measured
      the increase in digital pulse volume amplitude during reactive hyperemia, and the
      index of endothelial function, F-RHI, was defined as the ratio of post-deflation
      amplitude to baseline amplitude. RESULTS: In the linear regression model, male
      sex was associated with lower F-RHI. In sex-adjusted linear regression models,
      each of the variables; waist circumference, fasting glucose, glycated hemoglobin,
      triglycerides, body fat percentage, body mass index, current smoking, and
      impaired fasting glucose or diabetes were separately associated with lower F-RHI,
      and HDL cholesterol and resting heart rate were associated with higher F-RHI.HDL
      cholesterol, sex, body mass index, and current smoking entered a stepwise
      multivariable regression model, in which HDL cholesterol was associated with
      higher F-RHI, and smoking, male sex and body mass index were associated with
      lower F-RHI. This model explains 28.3% of the variability in F-RHI. CONCLUSIONS:
      F-RHI is associated with several cardio-metabolic risk factors; low level of HDL
      cholesterol, male sex, overweight and smoking being the most important predictors
      of a lowered endothelial function. A large part of variation in F-RHI remains
      accounted for by unknown factors.

PMID- 24118795
TI  - Design, synthesis, and biological evaluation of andrographolide derivatives as
      potent hepatoprotective agents.
AB  - Poor water solubility limits the clinical use of andrographolide and its
      derivatives. In an attempt to develop potent hepatoprotective drugs, a strategy
      was proposed to improve the aqueous solubility of andrographolide. Ten
      andrographolide derivatives were designed, synthesized, evaluated for aqueous
      solubility and in vivo hepatoprotective activity against CCl4 -induced liver
      injury in mice. As expected, the aqueous solubility of synthetic derivatives was
      effectively improved. All compounds demonstrated the effect of different degrees
      in improving the liver enzyme (ALT and AST) activity, especially the most
      promising compound 9d significantly improved liver enzyme activity, with high
      potency to be a new lead. 

PMID- 24118796
TI  - Back complaints in older adults: prevalence of neuropathic pain and its
      characteristics.
AB  - OBJECTIVE: Neuropathic symptoms are reported in 16-55.6% of patients with back
      pain. Studies were performed in various populations; however, none focused on
      older adults. The aim of the study was to assess prevalence of neuropathic pain
      in older adults with back pain. METHODS: Prevalence of neuropathic pain, measured
      with the Dolour Neuropathique en 4 questions (DN4), was assessed in the Back
      Complaints in the Elders study (Netherlands). Patients (>55 years) consulting
      their general practitioner with a new episode of back complaints were included.
      Two DN4-versions were used: one based on interview plus physical examination, the
      other based on interview alone. In the interview plus physical examination
      version, patients' and complaint characteristics were compared between groups
      with different scores (0, 1, 2, 3, and >=4). The DN4 interview-version compared
      patients with negative and positive scores. RESULTS: Of the 261 included patients
      available for analysis were 250 patients (95.8%) with the DN4 interview plus
      physical examination, and 259 patients (99.2%) with the DN4 interview. In DN4
      interview plus physical examination (N = 250), five patients (2%) scored positive
      (score >=4). Higher score was associated with pain radiating below the knee (P <
      0.001) and use of paracetamol (P = 0.02). In DN4 interview (N = 259), 29 (11.2%)
      patients scored positive (score >=3). Positive score was associated with higher
      body mass index (P = 0.01), pain radiating below the knee (P = 0.001), and use of
      paracetamol (P = 0.002). CONCLUSIONS: In older adults with back pain presenting
      with a new episode in primary care, prevalence of neuropathic pain is low and
      seems to be associated with pain radiating below the knee, use of paracetamol,
      and higher body mass index.

PMID- 24118797
TI  - Toll-like receptors and liver disease.
AB  - Toll-like receptors (TLRs) are pattern recognition receptors that play an
      important role in host defence by recognizing pathogen-associated molecular
      patterns (PAMP). Recent studies indicate that TLR signalling plays an important
      role in progression of chronic liver diseases. Ongoing clinical trials suggest
      that therapeutic manipulation of TLR pathways may offer novel means of reversing
      chronic liver diseases. Upon activation by their respective ligands, TLRs
      initiate an intracellular pro-inflammatory/anti-inflammatory signalling cascade
      via recruitment of various adaptor proteins. TLR associated signalling pathways
      are tightly regulated to keep a check on inappropriate production of pro
      inflammatory cytokines and interferons thereby preventing various autoimmune and
      inflammatory processes. Herein, we review the current state of knowledge of
      hepatic distribution, signalling pathways and therapeutic modulation of TLRs in
      chronic liver diseases. 

PMID- 24118798
TI  - Prospective study of exercise intervention in prostate cancer patients on
      androgen deprivation therapy.
AB  - INTRODUCTION: Androgen deprivation therapy (ADT) is an important component of
      modern prostate cancer treatment. Survival benefits from neo-adjuvant and
      adjuvant hormones may take years to manifest, and balancing this with potential
      morbidity of therapy can be challenging. This study aimed to assess whether
      education and short-term combined aerobic and resistance exercises could help to
      ameliorate the adverse side effects of ADT. METHODS: Eight hundred fifty-nine
      patients with relapsed or metastatic prostate cancer on leuprorelin acetate were
      allocated to three interventional streams based on patient preference and medical
      fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home)
      exercise or a support programme for those incapable of exercising (Support).
      Patients enrolled onto Face to Face underwent measurement of body composition and
      cardiorespiratory fitness variables at baseline and programme completion.
      Patients in the exercise streams were surveyed to determine the programme's
      impact on physical fitness and well-being. RESULTS: Statistically significant
      improvements (p < 0.001) were seen in all measured cardiorespiratory fitness and
      strength variables. Programme attrition rates were low (75/859; 8.7%), the
      primary reason for withdrawal being discontinuation of hormones (70%). Programme
      satisfaction was high, with 98% of surveyed patients reporting a positive impact
      on fitness and 97% planning to continue exercising after programme completion. At
      6 months, improved physical and emotional well-being was reported by 93 and 79%
      of patients, respectively. CONCLUSIONS: A short-term structured exercise
      intervention results in high compliance and significant improvements in muscle
      strength and cardiorespiratory fitness in prostate cancer patients on ADT.

PMID- 24118799
TI  - Epidemiology of biopsy-proven giant cell arteritis in South Australia.
AB  - BACKGROUND/AIM: To determine the epidemiology and clinical features of biopsy
      proven giant cell arteritis (GCA) in South Australia (SA). METHODS: Patients with
      biopsy-proven GCA were identified from pathology reports of temporal artery
      biopsies at SA Pathology laboratories, from 1 January 1992, to 31 July 2011.
      Epidemiological data were collected through patient questionnaires and
      standardised case note reviews. Incidence was estimated using Australian Bureau
      of Statistics population data for SA. Seasonality was analysed by Cosinor
      analysis, and time-to- event analysis was performed for the duration of steroid
      use. RESULTS: There were 314 cases of biopsy-proven GCA (72% female). The mean
      age at diagnosis of GCA was 78 years (interquartile range 72-82). The estimated
      population incidence for people over 50 was 3.2 per 100,000 person years. The
      female : male incidence ratio was 2.3 (P < 0.001), and incidence increased with
      each age decade. There was evidence of seasonal variation (P = 0.015), with
      higher rates observed in the summer months. Clinical data were available for 163
      patients (68% female, median age 78 years). The most common presenting clinical
      features were temporal headache (74%), visual disturbance (68.4%), jaw
      claudication (59.3%) and symptoms of polymyalgia rheumatica (56%). The median
      initial steroid dose was 60 mg, with median duration of steroid use 4.5 years.
      Corticosteroid side-effects were common, affecting 89%, with 34% reporting five
      or more. CONCLUSIONS: This is the first epidemiological study of Australian
      biopsy-proven GCA patients. Age at onset and gender associations were similar to
      other Western populations. There was a high burden of steroid use in these
      patients.

PMID- 24118800
TI  - High-resolution array-CGH in patients with oculocutaneous albinism identifies new
      deletions of the TYR, OCA2, and SLC45A2 genes and a complex rearrangement of the
      OCA2 gene.
AB  - Oculocutaneous albinism (OCA) is caused by mutations in six different genes, and
      their molecular diagnosis encompasses the search for point mutations and
      intragenic rearrangements. Here, we used high-resolution array-comparative genome
      hybridization (CGH) to search for rearrangements across exons, introns and
      regulatory sequences of four OCA genes: TYR, OCA2, TYRP1, and SLC45A2. We
      identified a total of ten new deletions in TYR, OCA2, and SLC45A2. A complex
      rearrangement of OCA2 was found in two unrelated patients. Whole-genome
      sequencing showed deletion of a 184-kb fragment (identical to a deletion
      previously found in Polish patients), whereby a large portion of the deleted
      sequence was re-inserted after severe reshuffling into intron 1 of OCA2. The high
      resolution array-CGH presented here is a powerful tool to detect gene
      rearrangements. Finally, we review all known deletions of the OCA1-4 genes
      reported so far in the literature and show that deletions or duplications account
      for 5.6% of all mutations identified in the OCA1-4 genes. 

PMID- 24118801
TI  - Dacryocystography in a cat with orbital pneumatosis.
AB  - A 2-year-old neutered male European short-haired cat was presented for a
      persistent discharge from the scar of previous left eye enucleation, performed 6
      months prior by the referring veterinarian. A surgical exploration of the orbit
      was performed and retained nictitating membrane glandular and conjunctival
      tissues were removed. Eleven days later, the cat developed an orbital pneumatosis
      caused by retrograde movement of air through a patent nasolacrimal system and
      diagnosed by survey radiographic examination of the skull. Nasolacrimal system
      patency was assessed by dacryocystography performed by injection of iodinated
      contrast medium under pressure into the orbital cavity. Computed tomography
      dacryocystography confirmed the radiographic findings. The condition resolved
      following dacryocystography, possibly as an inflammatory response to the contrast
      medium. To our knowledge, this is the first case of orbital pneumatosis reported
      in a cat.

PMID- 24118803
TI  - Implementation and performance evaluation of an emergency department primary
      practitioner physiotherapy service for patients with musculoskeletal conditions.
AB  - OBJECTIVE: The study aims to describe the implementation of a primary
      practitioner physiotherapy service within a large regional ED and to evaluate its
      impact on waiting time and length of stay. METHODS: Integration and scope of
      practice of the physiotherapy service within the ED were described. Retrospective
      analysis of waiting time and length of stay data for the 3 years, 1 October 2008
      to 30 September 2011, was performed. The performance of the physiotherapy service
      was compared with the Australasian College for Emergency Medicine (ACEM) waiting
      time guidelines, the Victorian Department of Health length of stay targets and to
      a similar group of patients seen by medical staff. RESULTS: The primary
      practitioner physiotherapy service saw 5641 patients of which 33% were less than
      18 years old. The most common presentations seen by the service were limb
      fractures, soft tissue injuries and low back pain. Ninety-two per cent of
      patients were seen within the ACEM waiting time guidelines, and 91% of patients
      who went home were discharged within 4 h. Non-randomised comparisons with similar
      patients seen by medical staff indicated that patients seen by the physiotherapy
      practitioner service had shorter waiting times and length of stay. CONCLUSIONS:
      The current study found that patients with musculoskeletal problems seen by a
      primary practitioner physiotherapy service had improved waiting times and length
      of stay relative to ACEM and Victorian Department of Health targets, and though
      constrained by a retrospective non-randomised design, to a similar group of
      patients seen by medical staff. Further evaluation of the physiotherapy
      practitioner service is required.

PMID- 24118802
TI  - Synthetic brominated furanone F202 prevents biofilm formation by potentially
      human pathogenic Escherichia coli O103:H2 and Salmonella ser. Agona on abiotic
      surfaces.
AB  - AIMS: Investigate the use of a synthetic brominated furanone (F202) against the
      establishment of biofilm by Salmonella ser. Agona and E. coli O103:H2 under
      temperature conditions relevant for the food and feed industry as well as under
      temperature conditions optimum for growth. METHODS AND RESULTS: Effect of F202 on
      biofilm formation by Salmonella ser. Agona and E. coli O103:H2 was evaluated
      using a microtiter plate assay and confocal microscopy. Effect of F202 on
      bacterial motility was investigated using swimming and swarming assays. Influence
      on flagellar synthesis by F202 was examined by flagellar staining. Results showed
      that F202 inhibited biofilm formation without being bactericidal. F202 was found
      to affect both swimming and swarming motility without, however, affecting the
      expression of flagella. CONCLUSIONS: F202 showed its potential as a biofilm
      inhibitor of Salmonella ser. Agona and E. coli O103:H2 under temperature
      conditions relevant for the feed and food industry as well as temperatures
      optimum for growth. One potential mode of action of F202 was found to be by
      targeting flagellar function. SIGNIFICANCE AND IMPACT OF THE STUDY: The present
      study gives valuable new knowledge to the potential use of furanones as a tool in
      biofilm management in the food and feed industry.

PMID- 24118804
TI  - NxrB encoding the beta subunit of nitrite oxidoreductase as functional and
      phylogenetic marker for nitrite-oxidizing Nitrospira.
AB  - Nitrospira are the most widespread and diverse known nitrite-oxidizing bacteria
      and key nitrifiers in natural and engineered ecosystems. Nevertheless, their
      ecophysiology and environmental distribution are understudied because of the
      recalcitrance of Nitrospira to cultivation and the lack of a molecular functional
      marker, which would allow the detection of Nitrospira in the environment. Here we
      introduce nxrB, the gene encoding subunit beta of nitrite oxidoreductase, as a
      functional and phylogenetic marker for Nitrospira. Phylogenetic trees based on
      nxrB of Nitrospira were largely congruent to 16S ribosomal RNA-based phylogenies.
      By using new nxrB-selective polymerase chain reaction primers, we obtained almost
      full-length nxrB sequences from Nitrospira cultures, two activated sludge
      samples, and several geographically and climatically distinct soils. Amplicon
      pyrosequencing of nxrB fragments from 16 soils revealed a previously unrecognized
      diversity of terrestrial Nitrospira with 1801 detected species-level operational
      taxonomic units (OTUs) (using an inferred species threshold of 95% nxrB
      identity). Richness estimates ranged from 10 to 946 coexisting Nitrospira species
      per soil. Comparison with an archaeal amoA dataset obtained from the same soils
      [Environ. Microbiol. 14: 525-539 (2012)] uncovered that ammonia-oxidizing archaea
      and Nitrospira communities were highly correlated across the soil samples,
      possibly indicating shared habitat preferences or specific biological
      interactions among members of these nitrifier groups.

PMID- 24118805
TI  - Lumbosacral epiduroscopy findings predict treatment outcome.
AB  - OBJECTIVE: The aim of this study was to evaluate the significance of diagnostic
      markers obtained through epiduroscopy by evaluating the accuracy of outcome
      prediction after treatment of epidural pathology using epiduroscopy. DESIGN: A
      prospective observational study of 139 patients was performed. Patients with
      chronic low back and leg pain were included. Of the 150 patients who underwent
      epiduroscopy in the year 2008 at a US hospital, 139 were available for evaluation
      at 1 month. STUDY: Outcome of treatment was predicted based on direct visual
      information (hyperemia, vascularity, and fibrosis) and mechanical information
      (pain to touch, contrast spread, and patency) obtained through epiduroscopy. MAIN
      OUTCOME MEASURES: Outcome of treatment was measured at 1 month. Accuracy of
      prediction of outcome was calculated using contingency tables and odds ratios.
      RESULTS: A prediction of outcome was made in 114 of 139 patients (82%). This
      prediction was correct in 89 of these 114 patients (accuracy of 78%). The
      sensitivity and specificity of epiduroscopy with respect to the prediction of
      outcome were 75% and 82%, respectively. These results were statistically
      significant (P < 0.01). In 25 of the 139 patients (18%), discrete epidural
      pathology was not observed. Nine of these 25 patients reported good relief after
      epiduroscopy. The sensitivity and specificity of epiduroscopy in the diagnosis of
      epidural pathology were 91% and 39%, respectively. These results were not
      statistically different (P > 0.1). CONCLUSION: Our results show that lumbosacral
      epiduroscopy predicts outcome of treatment accurately in the majority of
      patients. This suggests that information obtained through epiduroscopy may carry
      significant diagnostic and prognostic value.

PMID- 24118806
TI  - Neuroprotective potential of silymarin against CNS disorders: insight into the
      pathways and molecular mechanisms of action.
AB  - Silymarin, a C25 containing flavonoid from the plant Silybum marianum, has been
      the gold standard drug to treat liver disorders associated with alcohol
      consumption, acute and chronic viral hepatitis, and toxin-induced hepatic
      failures since its discovery in 1960. Apart from the hepatoprotective nature,
      which is mainly due to its antioxidant and tissue regenerative properties,
      Silymarin has recently been reported to be a putative neuroprotective agent
      against many neurologic diseases including Alzheimer's and Parkinson's diseases,
      and cerebral ischemia. Although the underlying neuroprotective mechanism of
      Silymarin is believed to be due to its capacity to inhibit oxidative stress in
      the brain, it also confers additional advantages by influencing pathways such as
      beta-amyloid aggregation, inflammatory mechanisms, cellular apoptotic machinery,
      and estrogenic receptor mediation. In this review, we have elucidated the
      possible neuroprotective effects of Silymarin and the underlying molecular
      events, and suggested future courses of action for its acceptance as a CNS drug
      for the treatment of neurodegenerative diseases. 

PMID- 24118807
TI  - Growth activity of gammaproteobacterial subgroups in waters off the west
      Antarctic Peninsula in summer and fall.
AB  - Characterizing both growth and abundance is important in understanding the role
      of bacterial communities in biogeochemical cycling of global oceans. However,
      these two quantities are seldom measured together for specific bacterial clades.
      Our goal was to examine growth and abundance of three gammaproteobacterial
      subgroups, including SAR86, at the single-cell level by microautoradiography
      combined with fluorescence in situ hybridization (FISH) in coastal waters of the
      west Antarctic Peninsula region during two austral summers and one austral fall.
      We found that the SAR86 clade was less abundant and grew more slowly than two
      related gammaproteobacterial clades, Ant4D3 and Arctic96B-16. Over 60% of Ant4D3
      and Arctic96B-16 cells incorporated leucine, while only 25% of SAR86 cells were
      active in both summer and fall. We also explored using the size of the FISH image
      as another measure of single-cell activity. There was a linear relationship
      between FISH cell size and incorporation of leucine for all bacteria, Ant4D3 and
      Arctic96B-16, but not for SAR86. FISH sizes of SAR86 cells were at least
      threefold smaller than cells in the other clades. Our results suggest slow growth
      of SAR86 in the perennially cold waters of the west Antarctic Peninsula. 

PMID- 24118809
TI  - Are we using too many antibiotics during pregnancy?

PMID- 24118810
TI  - Antenatal antibiotics: too much, too little, or just right?

PMID- 24118811
TI  - Author's response to: Risk factors of anal sphincter injury during delivery.

PMID- 24118812
TI  - Risk factors of anal sphincter injury during delivery.

PMID- 24118813
TI  - 'Pregnant pause': the need for an evidence-based approach for work leave in the
      prevention of preterm birth and low birthweight.

PMID- 24118814
TI  - Author's response to: 'Pregnant pause': the need for an evidence-based approach
      for work leave in the prevention of preterm birth and low birthweight.

PMID- 24118815
TI  - Does the SWEPOP (Swedish Pregnancy, Obesity and Pelvic Floor) study suffer from a
      selection bias?

PMID- 24118816
TI  - Authors' response to: Does the SWEPOP (Swedish Pregnancy, Obesity and Pelvic
      Floor) study suffer from a selection bias?

PMID- 24118817
TI  - A report from #BlueJC: can antenatal hypnosis reduce the use of pharmacological
      analgesia in labour?

PMID- 24118819
TI  - Will the next generation of basal insulins offer clinical advantages?
AB  - The 21st century has seen the arrival of several insulin analogue products and
      the refinement of insulin regimens, with widespread advocacy of continuous
      titration algorithms and earlier initiation of supplementary insulin therapy
      (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many
      insulin-treated diabetes patients remain in poor glycaemic control. This might
      reflect insufficient titration effort or lax adherence, but these issues could in
      some cases result from concerns about hypoglycaemia. Certainly there is scope for
      improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin,
      and three new products offer this prospect. Insulin degludec, now in clinical
      use, and PEGylated insulin lispro, in development, have greatly extended action
      profiles that result from two very different, but unique, mechanisms. With once
      daily dosing, these insulins produce stable PK/PD profiles at steady state,
      associated with a low incidence of hypoglycaemia. The feasibility of varied daily
      dose timing has also been confirmed with insulin degludec. High strength
      formulations of insulin glargine and insulin degludec offer the prospect of a
      reduced injection number/volume in high dose users, and in the case of glargine,
      the PK/PD profile might also be favourably modified. This review considers
      critically the clinical evidence and expectations we should have for these new
      basal insulins. 

PMID- 24118820
TI  - Naringin inhibits ROS-activated MAPK pathway in high glucose-induced injuries in
      H9c2 cardiac cells.
AB  - Naringin, an active flavonoid isolated from citrus fruit extracts, exhibits
      biological and pharmacological properties, such as antioxidant activity and
      antidiabetic effect. Mitogen-activated protein kinase (MAPK) signalling pathway
      has been shown to participate in hyperglycaemia-induced injury. The present study
      tested the hypothesis that naringin protects against high glucose (HG)-induced
      injuries by inhibiting MAPK pathway in H9c2 cardiac cells. To examine this, the
      cells were treated with 35 mM glucose (HG) for 24 hr to establish a HG-induced
      cardiomyocyte injury model. The cells were pre-treated with 80 MUM naringin for 2
      hr before exposure to HG. The findings of this study showed that exposure of H9c2
      cells to HG for 24 hr markedly induced injuries, as evidenced by a decrease in
      cell viability, increases in apoptotic cells and reactive oxygen species (ROS)
      production, as well as dissipation of mitochondrial membrance potential (MMP).
      These injuries were significantly attenuated by the pre-treatment of cells with
      either naringin or SB203580 (a selective inhibitor of p38 MAPK) or U0126 (a
      selective inhibitor of extracellular signal regulated kinase 1/2, ERK1/2) or
      SP600125 (a selective inhibitor of c-jun N-termanal kinase, JNK) before exposure
      to HG, respectively. Furthermore, exposure of cells to HG increased the
      phosphorylation of p38 MAPK, ERK1/2 and JNK. The increased activation of MAPK
      pathway was ameliorated by pre-treatment with either naringin or N-acetyl-L
      cysteine (NAC), a ROS scavenger, which also reduced HG-induced cytotoxicity and
      apoptosis, leading to increase in cell viability and decrease in apoptotic cells.
      In conclusion, our findings provide new evidence for the first time that naringin
      protects against HG-induced injuries by inhibiting the activation of MAPK (p38
      MAPK, ERK1/2 and JNK) and oxidative stress in H9c2 cells. 

PMID- 24118822
TI  - Skin cleansing practices for older people: a systematic review.
AB  - AIMS AND OBJECTIVES: To locate, summarise and critically analyse current
      knowledge about skin hygiene practices for older people. BACKGROUND: Maintaining
      personal hygiene for patients is one of the core elements of care in all fields
      of nursing. However, it is a subject that has been neglected in both research and
      education. Skin integrity is essential to the health and well-being of older
      people. Skin cleansing practices can contribute to the maintenance and promotion
      of skin integrity. It is therefore essential to have a robust evidence base for
      such practices. DESIGN: Literature review by searches of the electronic databases
      Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      Academic Search Premier, psycINFO, Web of Science, SCOPUS and the Cochrane
      Library, using firstly key words and exclusion criteria, then citations and
      reference searches. An integrative review method was used. Studies included were
      alternative bathing protocol or bathing product interventions. Seven studies met
      the methodological requirements for inclusion. CONCLUSIONS: There is a
      significant lack of high-quality research studies to provide a framework for
      guiding evidence-based skin cleansing practice. Current guidance is based on
      clinical expertise rather than on robust trial evidence. A research agenda has
      been developed which may become the basis for developing evidence-based, best
      practice guidelines. Future research must move beyond descriptive studies to
      include more robust methods of investigation. The lack of intervention studies
      limits the practice-guiding implications that can be gained from the current body
      of research. IMPLICATIONS FOR PRACTICE: Skin cleansing is one of the cornerstones
      of nursing practice, however, in the absence of a robust evidence base most such
      care is currently based on 'custom and practice'. There is a need to conduct
      further research into cleansing practices that will maintain or enhance skin
      health and skin integrity.

PMID- 24118821
TI  - Supporting a person-centred approach in clinical guidelines. A position paper of
      the Allied Health Community - Guidelines International Network (G-I-N).
AB  - BACKGROUND: A person-centred approach in the context of health services delivery
      implies a biopsychosocial model focusing on all factors that influence the
      person's health and functioning. Those wishing to monitor change should consider
      this perspective when they develop and use guidelines to stimulate active
      consideration of the person's needs, preferences and participation in goal
      setting, intervention selection and the use of appropriate outcome measures.
      OBJECTIVE: To develop a position paper that promotes a person-centred approach in
      guideline development and implementation. DESIGN, SETTING AND PARTICIPANTS: We
      used three narrative discussion formats to collect data for achieving consensus:
      a nominal group technique for the Allied Health Steering Group, an Internet
      discussion board and a workshop at the annual G-I-N conference. We analysed the
      data for relevant themes to draft recommendations. RESULTS: We built the position
      paper on the values of the biopsychosocial model. Four key themes for enhancing a
      person-centred approach in clinical guidelines emerged: (i) use a joint
      definition of health-related quality of life as an essential component of
      intervention goals, (ii) incorporate the International Classification of
      Functioning, Disability and Health (ICF) as a framework for considering all
      domains related to health, (iii) adopt a shared decision-making method, and (iv)
      incorporate patient-reported health outcome measures. The position statement
      includes 14 recommendations for guideline developers, implementers and users.
      CONCLUSION: This position paper describes essential elements for incorporating a
      person-centred approach in clinical guidelines. The consensus process provided
      information about barriers and facilitators that might help us develop strategies
      for implementing person-centred care.

PMID- 24118823
TI  - Localization and function of the accessory protein Mfa3 in Porphyromonas
      gingivalis Mfa1 fimbriae.
AB  - The fimbriae of Porphyromonas gingivalis, the causative agent of periodontitis,
      have been implicated in various aspects of pathogenicity, such as colonization,
      adhesion and aggregation. Porphyromonas gingivalis ATCC 33277 has two adhesins
      comprised of the FimA and Mfa1 fimbriae. We characterized the PGN0289 (Mfa3)
      protein, which is one of the three accessory proteins of Mfa1 fimbriae in P.
      gingivalis. The Mfa3 protein was present in two different sizes, 40 and 43 kDa,
      in the cell. The 43-kDa and 40-kDa Mfa3 were detected largely in the inner
      membrane and the outer membrane, respectively. Purified Mfa1 fimbriae contained
      the 40-kDa Mfa3 alone. Furthermore, the 40-kDa Mfa3 started with the Ala(44)
      residue of the deduced amino acid sequence, indicating that the N-terminal region
      of the nascent protein expressed from the mfa3 gene is processed in the transport
      step from the inner membrane into fimbriae. Immuno-electron microscopy revealed
      that Mfa3 localized at the tip of the fimbrial shaft. Interestingly, deletion of
      the mfa3 gene resulted in the absence of other accessory proteins, PGN0290 and
      PGN0291, in the purified Mfa1 fimbriae, suggesting that Mfa3 is required for
      integration of PGN0290 and PGN0291 into fimbriae. A double mutant of mfa3 and
      fimA genes (phenotype Mfa1 plus, FimA minus) showed increased auto-aggregation
      and biofilm formation similar to a double mutant of mfa1 and fimA genes
      (phenotype Mfa1(-) , FimA(-) ). These findings suggest that the tip protein Mfa3
      of the Mfa1 fimbriae may function in the integration of accessory proteins and in
      the colonization of P. gingivalis.

PMID- 24118824
TI  - Inhibition of placental growth factor improves surgical outcome of glaucoma
      surgery.
AB  - Excessive post-operative wound healing with subsequent scarring frequently leads
      to surgical failure of glaucoma filtration surgery (trabeculectomy). We
      investigated the hypothesis that placental growth factor (PlGF) plays a role in
      post-operative scar formation, and that it therefore may be a target for
      improvement of filtration surgery outcome. ELISA experiments showed that PlGF
      levels were significantly increased in aqueous humour of glaucoma patients and
      after VEGF treatment, which may indicate an important contribution of this growth
      factor to wound healing after trabeculectomy. Using a mouse model of glaucoma
      filtration surgery, we were able to show that intracameral injection of a
      previously characterized anti-PlGF antibody (ThromboGenics NV) significantly
      improved surgical outcome by increasing bleb survival and bleb area. This was
      associated with a significant reduction in post-operative proliferation,
      inflammation and angiogenesis during the first post-operative days after surgery,
      and with a decrease in collagen deposition at later stages. Furthermore,
      inhibition of PlGF seemed to be more effective than anti-VEGF-R2 treatment in
      improving surgical outcome, possibly via its additional effect on inflammation.
      These results render PlGF an appealing target for ocular wound healing and point
      to potential therapeutic benefits of PlGF inhibition for the prevention of
      surgical failure. 

PMID- 24118825
TI  - Synthesis and biological evaluation of heterocyclic carboxylic acyl shikonin
      derivatives.
AB  - A series of shikonin derivatives (1-13) that were acylated selectively by various
      thiophene or indol carboxylic acids at the side chain of shikonin were
      synthesized, and their biological activities were also evaluated as potential
      tubulin inhibitors. Among them, compound 3 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4
      dihydronaphthalen-2-yl)-4-methylpent-3-enyl 3-(1H-indol-3-yl)propanoate) and
      compound 8 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4
      methylpent-3-enyl 2-(thiophen-3-yl)acetate) exhibited good antiproliferative
      activity of A875 (IC50  = 0.005 +/- 0.001 MUm, 0.009  +/- 0.002 MUm) and HeLa
      (IC50  = 11.84 +/- 0.64 MUm, 4.62  +/- 0.31 MUm) cancer cell lines in vitro,
      respectively. Shikonin (IC50  = 0.46 +/- 0.002 MUm, 4.80 +/- 0.48 MUm) and
      colchicine (IC50  = 0.75 +/- 0.05 MUm, 17.79 +/- 0.76 MUm) were used as
      references. Meanwhile, they also showed the most potent growth inhibitory
      activity against tubulin (IC50 of 3.96  +/- 0.13 MUm and 3.05 +/- 0.30 MUm,
      respectively), which were compared with shikonin (IC50  =  15.20 +/- 0.25 MUm)
      and colchicine (IC50  = 3.50 +/- 0.35 MUm). Furthermore, from the results of flow
      cytometer, we found compound 3 can really inhibit HeLa cell proliferation and has
      low cell toxicity. Based on the preliminary results, compound 3 with potent
      inhibitory activity in tumor growth may be a potential anticancer agent. 

PMID- 24118826
TI  - Post-transplant recurrence of atypical hemolytic uremic syndrome in a patient
      with thrombomodulin mutation.
AB  - HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal
      failure. While "typical" HUS is usually associated with Shiga toxin-producing
      Escherichia coli infections and recovers in the majority of cases, aHUS is caused
      by mutations of complement components or antibodies against CFH leading to
      uncontrolled activation of alternative complement pathway and often to ESRD.
      Recently, THBD gene mutations have been reported in aHUS. Theoretically, the risk
      of disease recurrence after renal transplantation should be low because THBD is
      primarily a membrane-bound protein expressed by endothelial cells; however, a
      small proportion of THBD is present as a soluble form in plasma. We report the
      case of a 19-yr-old man with aHUS secondary to a THBD mutation that relapsed
      twice after two renal transplantations performed 12 yr apart. Despite successful
      control of HUS with plasma exchange and eculizumab after the second
      transplantation, the graft was ultimately lost due to severe steroid-resistant
      cellular rejection. The present report suggests that THBD mutations may favor
      relapse of aHUS after renal transplantation. 

PMID- 24118827
TI  - Echocardiographic predictors of exercise capacity and mortality in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) reduces exercise
      capacity, but lung function parameters do not fully explain functional class and
      lung-heart interaction could be the explanation. We evaluated echocardiographic
      predictors of mortality and six minutes walking distance (6MWD), a marker for
      quality of life and mortality in COPD. METHODS: Ninety COPD patients (GOLD
      criteria) were evaluated by body plethysmography, 6MWD and advanced
      echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).
      RESULTS: Mean 6MWD was 403 (+/- 113) meters. All 90 subjects had preserved left
      ventricular (LV) ejection fraction 64.3% +/- 8.6%. Stroke volume decreased while
      heart rate increased with COPD severity and hyperinflation. In 66% of patients,
      some degree of diastolic dysfunction was present. Mitral tissue Doppler data in
      COPD could be interpreted as a sign of low LV preload and not necessarily an
      intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR)
      increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p <
      0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD
      and a multivariable model incorporating heart function parameters (adjusted r2 =
      .511) compared well to a model with lung function parameters alone (adjusted r2 =
      .475). LV global longitudinal strain (p = 0.034) was the only independent
      predictor of mortality among all baseline, body plethysmographic and
      echocardiographic variables. CONCLUSIONS: Among subjects with moderate to severe
      COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise
      tolerance correlated with standard lung function parameters only in univariate
      models; in subsequent models including echocardiographic parameters, longer 6MWD
      correlated independently with milder TR, better DLCO SB, younger age and lower
      BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV
      preload, heart rate, as well as systolic and diastolic function. Our results
      highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.

PMID- 24118828
TI  - Genetic regulation of immunoglobulin E level in different pathological states:
      integration of mouse and human genetics.
AB  - Immunoglobulin E (IgE) first evolved in mammals. It plays an important role in
      defence against helminths and parasitic infection and in pathological states
      including allergic reactions, anti-tumour defence and autoimmune diseases.
      Elucidation of genetic control of IgE level could help us to understand
      regulation of the humoral immune response in health and disease, the etiology and
      pathogenesis of many human diseases, and to facilitate discovery of more
      effective methods for their prevention and cure. Herein we summarise progress in
      the genetics of regulation of IgE level in human diseases and show that
      integration of different approaches and use of animal models have synergistic
      effects in gaining new knowledge about both protective and pathological roles of
      this important antibody.

PMID- 24118829
TI  - Accumulation of geriatric conditions is associated with poor nutritional status
      in dependent older people living in the community and in nursing homes.
AB  - AIM: To clarify the association between nutritional status and the prevalence of
      geriatric conditions in dependent older adults. METHODS: A cross-sectional
      observational study of dependent older adults aged 65years or older who were
      living either in the community (n = 511, mean age 81.2years) or in nursing homes
      (n = 587, mean age 85.2years) was carried out. Data included the participants'
      demographic characteristics, basic activities of daily living, Charlson
      Comorbidity Index and the prevalence of eight geriatric conditions (visual
      impairment, hearing impairment, falls, bladder control problems, cognitive
      impairment, impaired mobility, swallowing disturbance and loss of appetite).
      Nutritional status was assessed by the Mini Nutritional Assessment short form
      (MNA-SF). RESULTS: Of 1098 participants, 21.4% (n = 235) were categorized as
      "malnourished", according to the MNA-SF classification. Participants in the
      "malnourished" group had a greater number of geriatric conditions than those in
      the other two groups. A higher prevalence of all the geriatric conditions except
      for falls was detected in the group with poorer nutritional status. Multivariate
      logistic regression analysis showed that malnutrition was associated with the
      number of geriatric conditions, but not with that of comorbidities, even after
      controlling for confounders. CONCLUSIONS: Malnutrition was confirmed to have
      significant associations with geriatric conditions in dependent older adults.

PMID- 24118830
TI  - Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to
      combination antiviral therapy - a pilot randomised clinical trial.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) utilises cholesterol and lipoprotein
      metabolism for replication and infectivity. Statins and omega-3 (n-3)
      polyunsaturated fatty acids (PUFA) have been shown to have antiviral properties
      in vitro. This open label pilot study evaluated the efficacy of fluvastatin
      (Lescol((r)) 40-80 mg) and n-3 PUFA (Omacor((r)) 1 g and 2-4 g) on HCV-RNA and
      lipoviral particles (LVP) in difficult to treat prior non-responders. METHODS:
      Patients (n = 60) were randomly allocated in a factorial design to: no active
      drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA +
      fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for
      12 weeks and followed up to week 24. Comparison was made between fluvastatin (n =
      24) vs no fluvastatin (n = 26) and n-3 PUFA high-dose (n = 17) vs low-dose (n =
      17) vs none (n = 16). The primary outcomes were change in total HCV-RNA, LVP and
      ALT at week 12 compared with baseline. Secondary outcome was change in interferon
      gamma-inducible protein-10 (IP10) as a measure of interferon activation. RESULTS:
      35% had compensated cirrhosis and 45% were prior null responders. There was no
      significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients
      receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those
      treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased
      median IP10 concentration by -39 pg/ml (-111, 7.0 pg/ml Q1-Q3). CONCLUSIONS:
      Fluvastatin and n-3 PUFAs have no effect on plasma HCV-RNA or LVP. The effect of
      low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a
      supplemental therapy to enhance interferon sensitivity.

PMID- 24118831
TI  - Promoting collaborative dementia care via online interprofessional education.
AB  - AIM: This study aimed to develop, implement and evaluate an online
      interprofessional education (IPE) dementia case study for health science
      students. The IPE initiative aimed to develop collaborative interprofessional
      capabilities and client-centred mindsets that underpin high-quality dementia
      care. METHOD: A mixed methods research design was used to assess students'
      values, attitudes and learning outcomes using an interprofessional socialization
      and valuing scale (ISVS) completed pre and post the online case study and via
      thematic analysis of free text responses. RESULTS: Students' ISVS scores improved
      significantly following online participation, and the qualitative results support
      a shift towards interprofessional collaboration and client-centred care.
      CONCLUSIONS: This online IPE case study was successful in developing the
      collaborative mindsets and interprofessional capabilities required by a future
      workforce to meet the complex, client-centred needs of people living with
      dementia.

PMID- 24118832
TI  - Fluorescence in situ hybridization probing of protozoal Entodinium spp. and their
      methanogenic colonizers in the rumen of cattle fed alfalfa hay or triticale
      straw.
AB  - AIMS: To develop and test a fluorescence in situ hybridization (FISH) based
      technique and to identify and quantify simultaneously those methanogenic
      populations colonizing Entodinium spp. in the rumen of cows fed different
      forages. METHODS AND RESULTS: New FISH probes targeting protozoal Entodinium spp.
      were designed and used together with FISH probes for methanogens in the cow
      rumen. The composition and relative abundance of methanogenic populations
      colonizing Entodinium simplex-, E. caudaum- and Entodinium furca-related
      populations were similar. Methanogens including Methanobrevibacter thaueri,
      Methanobrevibacter millerae and Methanobrevibacter smithii, and members of
      Methanomicrobium and Methanosphaera were generally the predominant colonizers of
      protozoa, regardless of the forage fed to cattle. Individual animals appeared to
      differ in which ruminal methanogenic populations colonized each of the individual
      Entodinium spp. CONCLUSIONS: Simultaneous FISH probing is shown here to be a
      reliable and effective approach to investigate the dynamics of symbiotic
      relationships between ruminal protozoa and methanogens at a single cell level.
      Phylogenetically closely related Entodinium spp. were colonized by similar
      methanogenic populations regardless of the forage fed. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first report of the methanogenic archaeal populations that
      specifically colonize Entodinium spp. as identified using simultaneous FISH
      probing.

PMID- 24118833
TI  - Retroperitoneal sarcomas: a review of disease spectrum, radiological features,
      characterisation and management.
AB  - Retroperitoneal sarcomas are a rare disease. The overall 5-year survival rate for
      these lesions remains low, and surgical management offers the only option for
      effective treatment and potential for cure. Radiotherapy is increasingly being
      employed in addition to standard surgical treatment. Improvements in cross
      sectional imaging have also facilitated better characterisation of lesions,
      preoperative planning and long-term follow-up. This article reviews the current
      literature and documents the various types of retroperitoneal sarcomas with a
      particular approach to their imaging features. We also highlight the pathology,
      diagnostic methods and most current management of these tumours. 

PMID- 24118834
TI  - Removing environmental sources of variation to gain insight on symbionts vs.
      transient microbes in high and low microbial abundance sponges.
AB  - In this study, we pursue unravelling the bacterial communities of 26 sponges,
      belonging to several taxonomical orders, and comprising low microbial abundance
      (LMA) and high microbial abundance (HMA) representatives. Particularly, we
      searched for species-specific bacteria, which could be considered as symbionts.
      To reduce temporal and spatial environmentally caused differences between host
      species, we sampled all the sponge species present in an isolated small rocky
      area in a single dive. The bacterial communities identified by pyrosequencing the
      16S rRNA gene showed that all HMA species clustered separated from LMA sponges
      and seawater. HMA sponges often had highest diversity, but some LMA sponges had
      also very diverse bacterial communities. Network analyses indicated that no core
      bacterial community seemed to exist for the studied sponges, not even for such a
      space and time-restricted sampling. Most sequences, particularly the most
      abundant ones in each species, were species-specific for both HMA and LMA
      sponges. The bacterial sequences retrieved from LMA sponges, despite being
      phylogenetically more similar to seawater, did not represent transient seawater
      bacteria. We conclude that sponge bacterial communities depend more on the host
      affiliation to the HMA or LMA groups than on host phylogeny. 

PMID- 24118835
TI  - Vasovagal rates in flouroscopically guided interventional procedures: a study of
      over 8,000 injections.
AB  - OBJECTIVE: To determine the rate of vasovagal (vv) complications in
      fluoroscopically guided interventional procedures. DESIGN: Retrospective case
      series analysis of prospectively collected data from March 8, 2004 to January 30,
      2009. SETTING: A single academic medical center. SUBJECTS: Four thousand one
      hundred eighty-three subjects undergoing 8,010 consecutive injections. OUTCOME
      MEASURES: Pearson's chi-square test was used to determine the relationship
      between categorical variables. RESULTS: A total of 8,010 injections, including
      epidural steroid injections, radiofrequency nerve ablations, medial branch
      blocks, hip injections, knee injections, and glenohumeral injections were
      performed. Overall vv reaction rate was 2.6%, with 0.8% of procedures resulting
      in early terminated due to vv reaction. Peripheral joint injections had a vv rate
      of 0.2%, all occurring in hip injections. Transforaminal epidural steroid
      injections had a vv rate of 3.5%. Diagnostic blocks of the medial branches had
      the highest rate of vv (5.1%). Other predictors of vv reactions were identified
      including preprocedure pain score visual analog scale <5 (P = 0.004), male gender
      (P < 0.001), and age less than 65 years old (P < 0.001). CONCLUSIONS: vv
      reactions have an overall low occurrence rate (2.6%) in interventional procedures
      ranging from 0% in peripheral knee and shoulder injections to 5.1% in medial
      branch blocks. Conservative treatment of vv reaction and willingness to terminate
      procedures resulted in no serious adverse events related to vv reaction in 8,010
      procedures.

PMID- 24118836
TI  - Targeted disruption of an EH-domain protein endocytic complex, Pan1-End3.
AB  - Pan1 is a multi-domain scaffold that enables dynamic interactions with both
      structural and regulatory components of the endocytic pathway. Pan1 is composed
      of Eps15 Homology (EH) domains which interact with adaptor proteins, a central
      region that is responsible for its oligomerization and C-terminal binding sites
      for Arp2/3, F-actin, and type-I myosin motors. In this study, we have
      characterized the binding sites between Pan1 and its constitutive binding partner
      End3, another EH domain containing endocytic protein. The C-terminal End3 Repeats
      of End3 associate with the N-terminal part of Pan1's central coiled-coil region.
      These repeats appear to act independently of one another as tandem, redundant
      binding sites for Pan1. The end3-1 allele was sequenced, and corresponds to a C
      terminal truncation lacking the End3 Repeats. Mutations of the End3 Repeats
      highlight that those residues which are identical between these repeats serve as
      contact sites for the interaction with Pan1. 

PMID- 24118837
TI  - Productivity and salinity structuring of the microplankton revealed by
      comparative freshwater metagenomics.
AB  - Little is known about the diversity and structuring of freshwater microbial
      communities beyond the patterns revealed by tracing their distribution in the
      landscape with common taxonomic markers such as the ribosomal RNA. To address
      this gap in knowledge, metagenomes from temperate lakes were compared to selected
      marine metagenomes. Taxonomic analyses of rRNA genes in these freshwater
      metagenomes confirm the previously reported dominance of a limited subset of
      uncultured lineages of freshwater bacteria, whereas Archaea were rare.
      Diversification into marine and freshwater microbial lineages was also reflected
      in phylogenies of functional genes, and there were also significant differences
      in functional beta-diversity. The pathways and functions that accounted for these
      differences are involved in osmoregulation, active transport, carbohydrate and
      amino acid metabolism. Moreover, predicted genes orthologous to active
      transporters and recalcitrant organic matter degradation were more common in
      microbial genomes from oligotrophic versus eutrophic lakes. This comparative
      metagenomic analysis allowed us to formulate a general hypothesis that oceanic-
      compared with freshwater-dwelling microorganisms, invest more in metabolism of
      amino acids and that strategies of carbohydrate metabolism differ significantly
      between marine and freshwater microbial communities. 

PMID- 24118838
TI  - Review article: burnout in emergency medicine physicians.
AB  - Training and the practice of emergency medicine are stressful endeavours, placing
      emergency medicine physicians at risk of burnout. Burnout syndrome is associated
      with negative outcomes for patients, institutions and the physician. The aim of
      this review is to summarise the available literature on burnout among emergency
      medicine physicians and provide recommendations for future work in this field. A
      search of MEDLINE (1946-present) (search terms: 'Burnout, Professional' AND
      'Emergency Medicine' AND 'Physicians'; 'Stress, Psychological' AND 'Emergency
      Medicine' AND 'Physicians') and EMBASE (1988-present) (search terms: 'Burnout'
      AND 'Emergency Medicine' AND 'Physicians'; 'Mental Stress' AND 'Emergency
      Medicine' AND 'Physicians') was performed. The authors focused on articles that
      assessed burnout among emergency medicine physicians. Most studies used the
      Maslach Burnout Inventory to quantify burnout, allowing for cross-study (and
      cross-country) comparisons. Emergency medicine has burnout levels in excess of
      60% compared with physicians in general (38%). Despite this, most emergency
      medicine physicians (>60%) are satisfied with their jobs. Both work-related
      (hours of work, years of practice, professional development activities, non
      clinical duties etc.) and non-work-related factors (age, sex, lifestyle factors
      etc.) are associated with burnout. Despite the heavy burnout rates among
      emergency medicine physicians, little work has been performed in this field.
      Factors responsible for burnout among various emergency medicine populations
      should be determined, and appropriate interventions designed to reduce burnout. 

PMID- 24118839
TI  - Changes in Pain Modulation Occur Soon After Whiplash Trauma but are not Related
      to Altered Perception of Distorted Visual Feedback.
AB  - OBJECTIVES: Widespread sensory hypersensitivity has been observed in acute
      whiplash associated disorders (WAD). Changes in descending pain modulation take
      part in central sensitization. However, endogenous pain modulation has never been
      investigated in acute WAD. Altered perception of distorted visual feedback has
      been observed in WAD. Both mechanisms (ie, pain modulation and perception of
      distorted visual feedback) may be different components of one integrated system
      orchestrated by the brain. This study evaluated conditioned pain modulation (CPM)
      in acute WAD. Secondly, we investigated whether changes in CPM are associated
      with altered perception of distorted visual feedback. METHODS: Thirty patients
      with acute WAD, 35 patients with chronic WAD and 31 controls were subjected to an
      experiment evaluating CPM and a coordination task inducing visual mediated
      changes between sensory feedback and motor output. RESULTS: A significant CPM
      effect was observed in acute WAD (P = 0.012 and P = 0.006), which was
      significantly lower compared to controls (P = 0.004 and P = 0.020). No obvious
      differences in CPM were found between acute and chronic WAD (P = 0.098 and P =
      0.041). Changes in CPM were unrelated to altered perception of distorted visual
      feedback (P > 0.01). CONCLUSION: Changes in CPM were observed in acute WAD,
      suggesting less efficient pain modulation. The results suggest that central pain
      and sensorimotor processing underlie distinctive mechanisms.

PMID- 24118840
TI  - Priming of mononuclear cells with a combination of growth factors enhances wound
      healing via high angiogenic and engraftment capabilities.
AB  - Recently, we demonstrated that a specific combination of growth factors enhances
      the survival, adhesion and angiogenic potential of mononuclear cells (MNCs). In
      this study, we sought to investigate the changes of the angiogenic potential of
      MNCs after short-time priming with a specific combination of growth factors. MNCs
      were isolated using density gradient centrifugation and incubated with a priming
      cocktail containing epidermal growth factor (EGF), insulin-like growth factor
      (IGF)-1, fibroblast growth factor (FGF)-2, FMS-like tyrosine kinase (Flt)-3L ,
      Angiopoietin (Ang)-1, granulocyte chemotactic protein (GCP)-2 and thrombopoietin
      (TPO) (all 400 ng/ml) for 15, 30 and 60 min. Wounds in nonobese diabetic-severe
      combined immune deficiency (NOD-SCID) mice were created by skin excision followed
      by cell transplantation. We performed a qRT-PCR analysis on the growth factor
      primed cells. The angiogenic factors vascular endothelial growth factor (VEGF)-A,
      FGF-2, hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and
      interleukin (IL)-8 and the anti-apoptotic factors IGF-1 and transforming growth
      factor-beta1 were significantly elevated in the MNCs primed for 30 min. (T30)
      compared with the non-primed MNCs (T0). The scratch wound assay revealed that T30
      conditioned media (CM) significantly increased the rate of fibroblast-mediated
      wound closure compared with the rates from T0-CM and human umbilical vein
      endothelial cells (HUVEC)-CM at 20 hrs. In vivo wound healing results revealed
      that the T30-treated wounds demonstrated accelerated wound healing at days 7 and
      14 compared with those treated with T0. The histological analyses demonstrated
      that the number of engrafted cells and transdifferentiated keratinocytes in the
      wounds were significantly higher in the T30-transplanted group than in the T0
      transplanted group. In conclusion, this study suggests that short-term priming of
      MNCs with growth factors might be alternative therapeutic option for cell-based
      therapies. 

PMID- 24118841
TI  - Enhancing health-care workers' understanding and thinking about people living
      with co-occurring mental health and substance use issues through consumer-led
      training.
AB  - BACKGROUND: Stigma and judgemental assumptions by health workers have been
      identified as key barriers to accessing health care for people living with co
      occurring mental health and substance use issues (dual diagnosis). OBJECTIVE: To
      evaluate the effectiveness of consumer-led training by people with dual diagnosis
      in improving the knowledge, understanding and role adequacy of community health
      staff to work with this consumer group. METHODS: A controlled before-and-after
      study design with four waves of quantitative data collection was used.
      Qualitative data were collected to explore participants' views about training.
      Participants were staff from two community health services from Victoria,
      Australia. Recruitment occurred across various work areas: reception, oral
      health, allied health, counselling and health promotion. At baseline, all
      participants attended a 4-h clinician-led training session. The intervention
      consisted of a 3-h consumer-led training session, developed and delivered by
      seven individuals living with dual diagnosis. Outcome measures included
      understanding of dual diagnosis, participants' feelings of role adequacy and role
      legitimacy, personal views, and training outcomes and relevance. RESULTS:
      Consumer-led training was associated with a significant increase in
      understanding. The combination of clinician-led and consumer-led training was
      associated with a positive change in role adequacy. CONCLUSIONS: Consumer-led
      training is a promising approach to enhance primary health-care workers'
      understanding of the issues faced by dual-diagnosis consumers, with such positive
      effects persisting over time. Used alongside other organizational capacity
      building strategies, consumer-led training has the potential to help address
      stigma and judgemental attitudes by health workers and improve access to services
      for this consumer group.

PMID- 24118842
TI  - Overall survival and toxicities regarding thoracic three-dimensional radiotherapy
      with concurrent chemotherapy for stage IV non-small cell lung cancer: results of
      a prospective single-center study.
AB  - BACKGROUND: The role of chemotherapy given concurrently with thoracic three
      dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not
      well defined. We performed this study to investigate overall survival and
      toxicity in patients with stage IV NSCLC treated with this modality. METHODS:
      From 2003 to 2010, 201 patients were enrolled in this study. All patients
      received chemotherapy with concurrent thoracic three-dimensional radiotherapy.
      The study endpoints were the assessment of overall survival (OS) and acute
      toxicity. RESULTS: For all patients, the median survival time (MST) was 10.0
      months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%,
      respectively. The MST was 14.0 months for patients who received a total radiation
      dose >=63 Gy to the primary tumor, whereas it was 8.0 months for patients who
      received a total dose <63 Gy (P = 0.000). On multivariate analysis, a total dose
      >=63 Gy, a single site of metastatic disease, and undergoing >=4 cycles of
      chemotherapy were independent prognostic factors for better OS (P = 0.007, P =
      0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was
      a marginally significant prognostic factor (P = 0.063). When the whole group was
      subdivided into patients with metastasis at a single site and multiple sites, a
      higher radiation dose to the primary tumor remained a significant prognostic
      factor for improved OS. For patients who received >=4 cycles of chemotherapy,
      high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the
      subgroup that received <4 chemotherapy cycles, the radiation dose was of marginal
      statistical significance regarding OS (P = 0.063). Treatment-related toxicity was
      found to be acceptable. CONCLUSIONS: Radiation dose to primary tumor, the number
      of metastatic sites, and the number of chemotherapy cycles were independent
      prognostic factors for OS in stage IV NSCLC patients treated with concurrent
      chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic
      radiotherapy was shown to play an important role in improving OS. TRIAL
      REGISTRATION: Registered on (ChiCTR-TNC-10001026).

PMID- 24118843
TI  - Validity and reliability of the modified Chinese version of the Older People's
      Quality of Life Questionnaire (OPQOL) in older people living alone in China.
AB  - AIMS AND OBJECTIVES: This study aimed to test the validity and reliability of a
      modified Chinese version of the OPQOL among older people living alone in China.
      BACKGROUND: China has an ageing population with an increasing number of older
      people living alone who may have a poorer quality of life (QoL) in the light of
      the traditional culture of collectivism and filial piety. An appropriate
      instrument is important to assess their QoL. The Older People's Quality of Life
      Questionnaire (OPQOL) was developed directly from the views of older people and
      has been validated in England. There has been no psychometric evaluation of the
      scale in China. METHODS: The OPQOL was translated and modified prior to being
      administered to a stratified random cluster sample of 521 older people living
      alone. Validity was assessed through convergent validity, discriminant validity
      and construct validity. Reliability was assessed through internal consistency and
      test-retest reliability. RESULTS: Exploratory factor analysis indicated eight
      factors accounting for 63.77% of the variance. The convergent validity was
      supported by moderate correlations with functional ability, social support and
      loneliness with Spearman's rho of -0.50, 0.49 and -0.53, respectively. The
      discriminant validity was confirmed by differentiating QoL scores between the
      depressed and non-depressed groups. The Cronbach's alpha coefficient was 0.90 for
      the total scale and over 0.70 for most of its dimensions. The 2-week test-retest
      reliability ranged from 0.53 to 0.87. CONCLUSIONS: The modified Chinese version
      of the Older People's Quality of Life has acceptable validity and reliability as
      a useful instrument to measure the QoL of older people living alone in China.

PMID- 24118844
TI  - Anterior colporrhaphy compared with collagen-coated transvaginal mesh for
      anterior vaginal wall prolapse: a randomised controlled trial.
AB  - OBJECTIVE: To investigate the anatomical cure rate and complications related to
      collagen-coated mesh for cystocele, compared with a conventional anterior
      colporrhaphy. DESIGN: A randomised controlled study. SETTING: Six departments of
      obstetrics and gynaecology in Norway, Sweden, Finland, and Denmark. POPULATION:
      Women aged 55 years or older, referred for surgery with a prolapse of the
      anterior vaginal wall of stage 2 or higher. METHODS: Women scheduled for primary
      cystocoele surgery were randomised to either anterior colporrhaphy or a collagen
      coated Prolene mesh. Power analysis indicated that 130 patients had to be
      randomised. All patients were evaluated using the Pelvic Organ Prolapse
      Quantification (POP-Q) measurement. Quality of life, symptoms, and sexual
      function were evaluated using the Pelvic Floor Impact Questionnaire, the Pelvic
      Floor Distress Inventory, and the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Questionnaire. MAIN OUTCOME MEASURES: The primary outcome was objective
      cure, defined as prolapse below POP-Q stage 2 at the 12-months follow-up.
      Secondary outcomes were quality of life, symptoms, and presence (or not) of
      complications. RESULTS: In total, 161 women were randomised to either anterior
      colporrhaphy or mesh (participant ages 64.9 +/- 6.4 years versus 64.7 +/- 6.6
      years, respectively; mean +/- SD). The objective cure rate was 39.8% (95% CI 28.6
      50.9%) in the anterior colporrhaphy group, compared with 88.1% (95% CI 80.7
      95.6%) in the mesh group (P < 0.001). Vaginal mesh exposure occurred in ten women
      (13.3%) and dyspareunia occurred in two women (2.7%, not significant) in the mesh
      group at the 12-months follow-up. Questionnaires revealed no difference between
      the groups. CONCLUSIONS: Our study demonstrates a significantly improved
      objective cure rate associated with a high exposure rate among women with mesh
      surgery as opposed to conventional surgery.

PMID- 24118846
TI  - Evaluation of accelerated collagen cross-linking for the treatment of melting
      keratitis in ten cats.
AB  - OBJECTIVES: Melting keratitis is a serious condition presenting a high risk of
      permanent blindness and is caused by infectious or noninfectious factors. In
      humans, the clinical efficacy of collagen cross-linking (CXL) has been described
      in the treatment of refractory infectious keratitis by arresting keratomalacia.
      The aim of this study was to evaluate the efficacy of accelerated CXL for the
      treatment of melting keratitis in cats. ANIMALS STUDIED: Ten cats were treated
      for unilateral melting keratitis by accelerated CXL. PROCEDURE: Corneas were
      irradiated by UVA (370 nm) at 30 mW/cm2 irradiance for 3 min after soaking with
      0.1% riboflavin in 20% dextran for 30 min (D1). Follow-up was conducted 3, 7, 14,
      and 30 days after treatment. RESULTS: Pain improvement was noted for all cases at
      D4 examination. Epithelial healing was observed at D8 for 9 of 10 cases and at
      D15 for 1 of 10 cases. Resolution of cellular infiltration was observed for all
      cases at D8 examination. The corneal vascularization was reduced for 9 of 10 cats
      by D31. At D31, all cases presented a variable degree of corneal fibrosis, but
      all eyes had visual function. No recurrent infection was observed. CONCLUSION:
      Accelerated CXL appears to be a valuable option for the treatment of melting
      keratitis in cats. All the cases have reached a satisfactory outcome despite the
      individual differences in the conditions prior to the CXL treatment and the
      variable presence of infectious agents.

PMID- 24118845
TI  - The role of the liver X receptor in chronic obstructive pulmonary disease.
AB  - BACKGROUND: There is a need for novel anti-inflammatory therapies to treat COPD.
      The liver X receptor (LXR) is a nuclear hormone receptor with anti-inflammatory
      properties. METHODS: We investigated LXR gene and protein expression levels in
      alveolar macrophages and whole lung tissue from COPD patients and controls, the
      effect of LXR activation on the suppression of inflammatory mediators from LPS
      stimulated COPD alveolar macrophages, and the effect of LXR activation on the
      induction of genes associated with alternative macrophage polarisation. RESULTS:
      The levels of LXR mRNA were significantly increased in whole lung tissue extracts
      in COPD patients and smokers compared to non-smokers. The expression of LXR
      protein was significantly increased in small airway epithelium and alveolar
      epithelium in COPD patients compared to controls. No differences in LXR mRNA and
      protein levels were observed in alveolar macrophages between patient groups. The
      LXR agonist GW3965 significantly induced the expression of the LXR dependent
      genes ABCA1 and ABCG1 in alveolar macrophage cultures. In LPS stimulated alveolar
      macrophages, GW3965 suppressed the production of CXCL10 and CCL5, whilst
      stimulating IL-10 production. CONCLUSIONS: GW3965 did not significantly suppress
      the production of TNFalpha, IL-1beta, or CXCL8. Our major finding is that LXR
      activation has anti-inflammatory effects on CXC10, CCL5 and IL-10 production from
      alveolar macrophages.

PMID- 24118847
TI  - The neuro-immune axis: prospect for novel treatments for mental disorders.
AB  - Disturbed bidirectional pathways between the (central) nervous system and immune
      system have been implicated in various mental disorders, including depressive and
      neurodevelopmental disorders. In this minireview, the role of the neuro-immune
      axis and its targetability in relation to major depression and autism spectrum
      disorder will be discussed. All together, the management of these and possibly
      other multi-factorial mental disorders needs a new and integrated therapeutic
      approach. Pharmacologically bioactive molecules as well as medical nutrition
      targeting the (gut)-immune-brain axis could be such an approach. 

PMID- 24118849
TI  - Ze'ev Ronai.

PMID- 24118848
TI  - Left ventricular myocardial performance index change for detection of acute
      cellular rejection in pediatric heart transplantation.
AB  - EMB, the gold standard for diagnosis of ACR, poses unique risks in children.
      Limited cross-sectional data have associated LV MPI with ACR. We hypothesize that
      a relative change in MPI from baseline without ACR to the time of ACR will better
      detect ACR than an absolute threshold LV MPI value. We identified 40 children
      with ACR >=60 days post-transplant matching them by age and time from
      transplantation to 40 children without ACR. There was a significant increase in
      LV MPI at time of ACR vs. baseline (0.59 +/- 0.17 vs. 0.41 +/- 0.11; p < 0.001).
      There was no difference in LV MPI between baseline and follow-up (0.41 +/- 0.11
      vs. 0.42 +/- 0.11; p = 0.65). An absolute increase in LV MPI of >=0.47 had 82.5%
      sensitivity and 85% specificity for ACR, whereas an increase in LV MPI from
      baseline of >=20.4% was 90% sensitive and 100% specific. Serial measurement of LV
      MPI appears to be a sensitive and specific marker of ACR. LV MPI shows good
      interobserver agreement and increases at the time of EMB-proven ACR with
      subsequent resolution to baseline measurements upon EMB-proven resolution of ACR.
      Future studies in larger, prospective cohorts should be undertaken to validate
      these findings. 

PMID- 24118850
TI  - Effect of androgen deprivation therapy on muscle attenuation in men with prostate
      cancer.
AB  - INTRODUCTION: Aging skeletal muscle is associated with not only a reduction in
      muscle size and strength but also in muscle quality which reflects an increase in
      fatty infiltration of muscle. In men with prostate cancer, androgen deprivation
      therapy (ADT) accelerates this loss of muscle size and strength, but it is
      unknown if muscle quality is also adversely affected. Therefore, we examined the
      effects of ADT on muscle attenuation, an indirect measure of intramuscular lipid
      content, as well as the muscle cross-sectional area (CSA) in men with prostate
      cancer. METHODS: Pre- and post-CT scans of the pelvis in 39 men aged 49-78 years
      receiving leuprorelin were examined. The time between baseline and follow-up
      scans was 14.6-20 weeks after the commencement of ADT. Changes in skeletal muscle
      attenuation in Hounsfield units of the rectus femoris and the CSA of the rectus
      femoris, sartorius and quadricep muscles were assessed. RESULTS: Muscle
      attenuation of the rectus femoris muscle was significantly reduced following the
      initiation of ADT by 18.9% (P < 0.001). In addition, there was a significant
      decrease (P < 0.001) in the CSA for the sartorius, quadriceps and rectus femoris
      muscles. There was no effect of Zometa on muscle attenuation or muscle CSA.
      CONCLUSIONS: Our results indicate that not only muscle size but also muscle
      quality may be adversely affected by the undertaking of ADT in men with prostate
      cancer. Consequently, interventions to counteract deteriorations to both muscle
      mass and possibly muscle quality should be considered in men receiving ADT.

PMID- 24118852
TI  - Hypertension prevalence, awareness, and control in Arab countries: a systematic
      review.
AB  - One billion of the world's population has hypertension, resulting in four million
      deaths per year. Data on the prevalence of hypertension in the Arab world are
      very limited. This review summarizes existing knowledge regarding prevalence,
      awareness, and control of hypertension in Arab countries. The PubMed, Cochrane
      Library, Scopus, and CINAHL databases were searched for publications on HTN among
      Arab people from 1980 to January 2011. Only 13 studies were identified in the
      literature from 10 Arab countries. The overall estimated prevalence of
      hypertension was 29.5% (n = 45 379), which indicates a higher prevalence of
      hypertension among Arabs compared to people from the USA (28%) and sub-Saharan
      African (27.6%). Awareness of hypertension was reported for 46% of the studies
      and varied from 18% (Jordan) to 79.8% (Syria). The control rate varied from 56%
      (Tunisia) to 92% (Egypt and Syria). The prevalence of hypertension was found to
      increase with age, occurring more frequently in Arab women.

PMID- 24118853
TI  - Cognitive function after cardiac arrest and temperature management; rationale and
      description of a sub-study in the Target Temperature Management trial.
AB  - BACKGROUND: Mild to moderate cognitive impairment is common amongst long-term
      survivors of cardiac arrest. In the Target Temperature Management trial (TTM
      trial) comatose survivors were randomized to 33 degrees C or 36 degrees C
      temperature control for 24 hours after cardiac arrest and the effects on survival
      and neurological outcome assessed. This protocol describes a sub-study of the TTM
      trial investigating cognitive dysfunction and its consequences for patients' and
      relatives' daily life. METHODS/DESIGN: Sub-study sites in five European countries
      included surviving TTM patients 180 days after cardiac arrest. In addition to the
      instruments for neurological function used in the main trial, sub-study patients
      were specifically tested for difficulties with memory (Rivermead Behavioural
      Memory Test), attention (Symbol Digit Modalities Test) and executive function
      (Frontal Assessment Battery). Cognitive impairments will be related to the
      patients' degree of participation in society (Mayo-Portland Adaptability
      Inventory-4), health related quality of life (Short Form Questionnaire-36v2(c)),
      and the caregivers' situation (Zarit Burden Interview(c)). The two intervention
      groups (33 degrees C and 36 degrees C) will be compared with a group of
      myocardial infarction controls. DISCUSSION: This large international sub-study of
      a randomized controlled trial will focus on mild to moderate cognitive impairment
      and its consequences for cardiac arrest survivors and their caregivers. By using
      an additional battery of tests we may be able to detect more subtle differences
      in cognitive function between the two intervention groups than identified in the
      main study. The results of the study could be used to develop a relevant
      screening model for cognitive dysfunction after cardiac arrest. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01946932.

PMID- 24118854
TI  - Mutations of flagellar genes fliC12, fliA and flhDC of Edwardsiella tarda
      attenuated bacterial motility, biofilm formation and virulence to fish.
AB  - AIMS: The aim of this study was to investigate functions of flagellar genes
      fliC2, fliC12, fliA and flhDC in a bacterial fish pathogen Edwardsiella tarda.
      METHODS AND RESULTS: In this study, functions of flagellar genes, fliC2, fliC12
      (fliC1 + fliC2), fliA and flhDC (flhD + flhC) of Edw. tarda H1 were analysed by
      constructing in-frame deletion mutants respectively and complementary strains
      fliC2(+) and fliA(+) . Electron microscopy revealed that in-frame deletion of
      fliC12, fliA and flhDC significantly impaired the number and length of flagellar
      filaments, resulting in loss of both swimming and swarming motilities of the
      bacteria. In addition, compared to the wild-type strain and complementary
      strains, the flagellum-impaired mutants exhibited reduced biofilm formation
      ability, showed decreased ability in adherence and internalization to Epithelioma
      papulosum cyprini (EPC) cells and reduced pathogenicity to zebrafish.
      CONCLUSIONS: These results indicated that fliC12, fliA and flhDC of Edw. tarda
      played essential roles in flagellar filaments structure, bacteria motility,
      biofilm formation, adherence, internalization and pathogenicity of this
      bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that
      flagella function in facilitating virulence and it may provide a new target for
      vaccines against Edw. tarda infection.

PMID- 24118855
TI  - Carotid ultrasound examination as an aging and disability marker.
AB  - AIM: To explore the usefulness of carotid ultrasound examination as a marker of
      aging and predictor of disability among older people. METHODS: Carotid
      ultrasound, measuring carotid intima media thickness (CIMT) and recording the
      presence of plaques, was carried out in 152 adults aged 29-59 years (47 women)
      and in 107 older adults aged 61-88 years (86 women). In all, clinical routine
      laboratory parameters and lymphocyte telomere length as T/S ratio were measured.
      Among older adults, 12-min walk, timed up and go, hand grip and quadriceps
      strength were determined. RESULTS: CIMT was significantly higher among older
      people and T/S ratio was significantly higher in young women. Carotid plaques
      were found in one adult and 17 older people. A multiple regression analysis
      accepted age, systolic blood pressure and T/S ratios as independent predictors of
      CIMT (R(2) = 0.51). Among older people, a logistic regression accepted age and
      the presence of carotid plaques as significant predictors of a 12-min walk speed
      below 1 m/s. CONCLUSIONS: An abnormal 12-min walk as an indicator of functional
      decline among older people is associated with the presence of carotid artery
      plaques. CIMT is independently associated with age.

PMID- 24118851
TI  - Explaining bathymetric diversity patterns in marine benthic invertebrates and
      demersal fishes: physiological contributions to adaptation of life at depth.
AB  - Bathymetric biodiversity patterns of marine benthic invertebrates and demersal
      fishes have been identified in the extant fauna of the deep continental margins.
      Depth zonation is widespread and evident through a transition between shelf and
      slope fauna from the shelf break to 1000 m, and a transition between slope and
      abyssal fauna from 2000 to 3000 m; these transitions are characterised by high
      species turnover. A unimodal pattern of diversity with depth peaks between 1000
      and 3000 m, despite the relatively low area represented by these depths. Zonation
      is thought to result from the colonisation of the deep sea by shallow-water
      organisms following multiple mass extinction events throughout the Phanerozoic.
      The effects of low temperature and high pressure act across hierarchical levels
      of biological organisation and appear sufficient to limit the distributions of
      such shallow-water species. Hydrostatic pressures of bathyal depths have
      consistently been identified experimentally as the maximum tolerated by shallow
      water and upper bathyal benthic invertebrates at in situ temperatures, and
      adaptation appears required for passage to deeper water in both benthic
      invertebrates and demersal fishes. Together, this suggests that a hyperbaric and
      thermal physiological bottleneck at bathyal depths contributes to bathymetric
      zonation. The peak of the unimodal diversity-depth pattern typically occurs at
      these depths even though the area represented by these depths is relatively low.
      Although it is recognised that, over long evolutionary time scales, shallow-water
      diversity patterns are driven by speciation, little consideration has been given
      to the potential implications for species distribution patterns with depth.
      Molecular and morphological evidence indicates that cool bathyal waters are the
      primary site of adaptive radiation in the deep sea, and we hypothesise that
      bathymetric variation in speciation rates could drive the unimodal diversity
      depth pattern over time. Thermal effects on metabolic-rate-dependent mutation and
      on generation times have been proposed to drive differences in speciation rates,
      which result in modern latitudinal biodiversity patterns over time. Clearly, this
      thermal mechanism alone cannot explain bathymetric patterns since temperature
      generally decreases with depth. We hypothesise that demonstrated physiological
      effects of high hydrostatic pressure and low temperature at bathyal depths,
      acting on shallow-water taxa invading the deep sea, may invoke a stress-evolution
      mechanism by increasing mutagenic activity in germ cells, by inactivating
      canalisation during embryonic or larval development, by releasing hidden
      variation or mutagenic activity, or by activating or releasing transposable
      elements in larvae or adults. In this scenario, increased variation at a
      physiological bottleneck at bathyal depths results in elevated speciation rate.
      Adaptation that increases tolerance to high hydrostatic pressure and low
      temperature allows colonisation of abyssal depths and reduces the stress
      evolution response, consequently returning speciation of deeper taxa to the
      background rate. Over time this mechanism could contribute to the unimodal
      diversity-depth pattern.

PMID- 24118856
TI  - Unsymmetrical oxovanadium complexes derived from salicylaldehyde and
      phenanthroline: synthesis, DNA interactions, and antitumor activities.
AB  - Two unsymmetrical oxovanadium complexes incorporating salicylaldehyde derivate
      and phenanthroline [VO(DESAA)(phen)] (1), (DESAA = 4
      (diethylamino)salicylaldehyde anthranilic acid, phen = phenanthroline) and
      [VO(CLSAA)(phen)] (2), (CLSAA = 5-chlorosalicylaldehyde anthranilic acid)] have
      been synthesized and characterized. The interactions of the complexes with CT-DNA
      were studied using different techniques. Complexes 1 and 2 interact with CT-DNA
      by intercalative modes and can efficiently cleave pBR322 DNA after light
      irradiation. The two complexes showed high cytotoxic activities against myeloma
      cell (Ag8.653) and gliomas cell (U251) lines. Interestingly, complex 1 exhibited
      greater antitumor efficiency, larger binding affinity with CT-DNA, and better
      cleaving ability than those of complex 2. In addition, their antitumor mechanism
      has been analyzed by using cell cycle analysis, apoptosis, and Annexin V-FITC/PI
      assay. The results showed that complex 1 can cause G2/M-phase arrest of the cell
      cycle, exhibit a significantly induced apoptosis in Ag8.653 cells, and display
      typical morphological apoptotic characteristics. These complexes induced
      proliferative suppression of Ag8.653 cells via the induction of apoptosis. 

PMID- 24118857
TI  - Non-high-density lipoprotein cholesterol independently predicts new onset of non
      alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with
      increased cardiovascular disease (CVD) risk. Non-high-density lipoprotein
      cholesterol (non-HDL-C), i.e. total cholesterol minus HDL, is a well-established
      risk factor for CVD; however, its association with NAFLD development has not been
      established. Our aim was to test whether non-HDL-C is an independent predictor of
      new onset of NAFLD. METHODS: A prospective cohort study of 213 subjects from the
      general population, without liver disease, was studied. Evaluation of medical
      history, dietary and physical activity habits, fasting blood tests and
      ultrasonographic evidence of NAFLD was performed at baseline and after a 7-year
      follow-up by identical protocols. RESULTS: From 147 patients that did not have
      NAFLD at baseline, 28 (19%) developed NAFLD at the 7-year follow-up. The baseline
      levels of non-HDL-C were higher among subjects who developed NAFLD (179.5 +/-
      37.1 vs. 157.3 +/- 35.1 mg/dl, P = 0.003). Non-HDL-C independently predicted new
      onset of NAFLD adjusting for age, gender, BMI or waist circumference, lifestyle
      and serum insulin (OR = 1.02 for every mg/dl increment, 1.01-1.04 95% CI, P =
      0.008). Non-HDL-C was a stronger predictor for NAFLD than total cholesterol, low
      density lipoprotein cholesterol, triglycerides and HDL. No patients with non-HDL
      C < 130 mg/dl developed NAFLD, whereas 20.8% of those with values between 130 to
      160 and 24.6% of those with values >160 mg/dl developed NAFLD (P for trend =
      0.015). CONCLUSIONS: Non-HDL-C is an independent predictor for NAFLD and a
      stronger predictor than other lipoproteins. This association may stem from the
      combined hepato-toxic effect of non-HDL-C and may explain the association between
      NAFLD and CVD.

PMID- 24118858
TI  - Malignant transformation of well-differentiated papillary mesothelioma 13 years
      after the diagnosis: a case report.
AB  - Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumour
      affecting mostly the peritoneum of women in their reproductive age, but it may
      occur also at other sites, including the pleura. It is considered a specific
      pathological entity different from diffuse malignant mesothelioma as it displays
      a characteristic histological pattern and is associated with a slowly progressive
      clinical course. We report the case of a 79-year-old man with a history of right
      pleural WDPM at age 64, which was successfully treated with chemotherapy,
      radiotherapy and talc pleurodesis. Thirteen years after the first diagnosis, he
      presented with mediastinal lymph nodes metastasis and with an extremely rare
      pattern of tracheal and bronchial infiltration that was detected at bronchoscopy.
      Biopsy samples revealed loss of histological differentiation of the neoplastic
      cells. This case report highlights that WDPM is a tumour of uncertain malignant
      potential that may undergo transformation over many years. Finally, the role of
      immunohistochemistry in the diagnosis of WDPM and the possible mechanisms leading
      to this unique way of metastatisation are discussed. 

PMID- 24118859
TI  - Alcohol-related violence presenting to the emergency department: is 'glassing'
      the big issue?
AB  - OBJECTIVE: The study aims to describe the characteristics of patients presenting
      to EDs within Queensland, Australia with injuries because of assault with a glass
      implement ('glassing') and to set this within the broader context of
      presentations because of alcohol-related violence. METHODS: This is an analysis
      of prospectively collected ED injury surveillance data collated by the Queensland
      Injury Surveillance Unit between 1999 and 2011. Cases of injury because of
      alcohol-related violence were identified and analysed using coded fields
      supplemented with qualitative data contained within the injury description text.
      Descriptive statistics were used to assess the characteristics of injury
      presentations because of alcohol-related violence. Violence included
      interpersonal violence and aggression (verbal aggression and object violence).
      RESULTS: A total of 4629 cases were studied. The study population was
      predominantly men (72%) and aged 18 to 24 (36%), with men in this age group
      comprising more than a quarter of the study population (28%). Nine per cent of
      alcohol-related assault injuries were a consequence of 'glassing'. The home was
      the most common location for alcohol-related violence (31%) and alcohol-related
      'glassings' (33%). Overall, the most common glass object involved was a bottle
      (75%); however, within licensed venues an even mix of a drinking glass (44%) and
      glass bottle (45%) was identified. CONCLUSIONS: Contrary to public perception
      generated by media, 'glassing' incidents, particularly at licensed venues,
      constitute a relatively small proportion of all alcohol-related violence. The
      current study highlights the predominance of young men injured following alcohol
      related violence, demonstrating a key focus area within the population for aiming
      prevention strategies.

PMID- 24118860
TI  - Metabolic syndrome components and their response to lifestyle and metformin
      interventions are associated with differences in diabetes risk in persons with
      impaired glucose tolerance.
AB  - AIMS: To determine the association of metabolic syndrome (MetS) and its
      components with diabetes risk in participants with impaired glucose tolerance
      (IGT), and whether intervention-related changes in MetS lead to differences in
      diabetes incidence. METHODS: We used the National Cholesterol Education
      Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at
      baseline and intervention-related changes of its components to predict incident
      diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants
      with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to
      treat analysis, the demographic-adjusted hazard ratios (95% confidence interval)
      for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7
      (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups,
      respectively. Higher levels of fasting plasma glucose and triglycerides at
      baseline were independently associated with increased risk of diabetes. Greater
      waist circumference (WC) was associated with higher risk in placebo and lifestyle
      groups, but not in the metformin group. In a multivariate model, favourable
      changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol
      (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS
      and some of its components are associated with increased diabetes incidence in
      persons with IGT in a manner that differed according to DPP intervention. After
      hyperglycaemia, the most predictive factors for diabetes were baseline
      hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC.
      Targeting these cardiometabolic risk factors may help to assess the benefits of
      interventions that reduce diabetes incidence.

PMID- 24118861
TI  - Applications of basic fibroblastic growth factor (FGF-2, bFGF) in dentistry.
AB  - Recent developments in research have been based on the maintenance and
      regeneration of natural organs and tissues; among such developments is the use of
      growth factors (GFs). The use of basic fibroblastic growth factors (bFGF) may be
      indicated in different disciplines of dentistry such as periodontics and dental
      traumatology. These cells' ability to induce proliferation and differentiation of
      cells may make GFs a useful source for the development of natural structures.
      This mini-review will discuss how bFGF can be beneficial to dentistry in relation
      to 1) re-implantation/autotransplantation of avulsed teeth and 2) periodontal
      regeneration. 

PMID- 24118862
TI  - Investigation of the binding and cleavage characteristics of N1 neuraminidases
      from avian, seasonal, and pandemic influenza viruses using saturation transfer
      difference nuclear magnetic resonance.
AB  - OBJECTIVES: The main function of influenza neuraminidase (NA) involves enzymatic
      cleavage of sialic acid from the surface of host cells resulting in the release
      of the newly produced virions from infected cells, as well as aiding the movement
      of virions through sialylated mucus present in the respiratory tract. However,
      there has previously been little information on the binding affinity of different
      forms of sialylated glycan with NA. Our objectives were then to investigate both
      sialic acid binding and cleavage of neuraminidase at an atomic resolution level.
      DESIGN: Nuclear magnetic resonance (NMR) spectroscopy was used to investigate pH
      and temperature effects on binding and cleavage as well as to interrogate the
      selectivity of human-like or avian-like receptors for influenza neuraminidase N1
      derived from a range of different influenza virus strains including human
      seasonal H1N1, H1N1pdm09 and avian H5N1. RESULTS: We demonstrated that an acidic
      pH and physiological temperature are required for efficient NA enzymatic
      activity; however a change in the pH had a minimum effect on the NA-sialic acid
      binding affinity. Our data comparing alpha-2,3- and alpha-2,6-sialyllactose
      indicated that the variation in neuraminidase activity on different ligands
      correlated with a change in binding affinity. Epitope mapping of the
      sialylglycans interacting with NAs from different viral origin showed different
      binding profiles suggesting that different binding conformations were adopted.
      CONCLUSIONS: The data presented in this study demonstrated that physicochemical
      conditions (pH in particular) could affect the NA enzymatic activity with minor
      effect on ligand binding. NA cleavage specificity seemed to be associated with a
      difference in binding affinity to different ligands, suggesting a relationship
      between the two events. These findings have implications regarding the
      replication cycle of influenza infection in the host where different sialidase
      activities would influence penetration through the respiratory mucin barrier and
      the release of the newly generated virus from the infected cells.

PMID- 24118863
TI  - Use of prescription contraceptive methods in the UK general population: a primary
      care study.
AB  - OBJECTIVE: To determine prescription contraceptive use in the UK. DESIGN:
      Observational study using a primary care database. SETTING: The Health
      Improvement Network (THIN). POPULATION: Women in THIN aged 12-49 years in 2008,
      registered with their primary care doctor for at least 5 years, and with a
      prescription history of at least 1 year were included. METHODS: THIN was searched
      using the Read and MULTILEX codes for the following methods: combined oral
      contraceptives (COCs), progestogen-only pills (POPs), copper intrauterine devices
      (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS),
      progestogen-only implants, progestogen-only injections, and contraceptive
      patches. MAIN OUTCOME MEASURES: Prevalence, switching, and duration of
      prescriptions. RESULTS: A cohort of 194 054 women was identified. The prevalence
      of contraceptive use was: COCs, 16.2% (95% confidence interval, 95% CI 16.1
      16.3%); POPs, 5.6% (95% CI 5.5-5.6%); Cu-IUD, 4.5% (95% CI 4.4-4.5%); LNG-IUS,
      4.2% (95% CI 4.1-4.2%); progestogen-only implants, 1.5% (95% CI 1.5-1.6%);
      progestogen-only injections, 2.4% (95% CI 2.3-2.4%); and contraceptive patches,
      0.1% (95% CI 0.1-0.2%). Within 1 year, 9.8% of new COC users switched to
      alternative COCs, and 9.0% changed to a different method. Among new COC users who
      did not switch method, 34.8% did not continue use beyond 3 months, and were no
      longer using a prescription contraceptive. CONCLUSIONS: Among users of oral
      contraceptives who did not switch method, over one-third did not continue use
      beyond 3 months. This supports current UK guidelines recommending a follow-up
      consultation with a healthcare professional 3 months after the first prescription
      of COCs.

PMID- 24118864
TI  - Genomic signatures of obligate host dependence in the luminous bacterial symbiont
      of a vertebrate.
AB  - The majority of bacteria engaged in bioluminescent symbiosis are environmentally
      acquired and facultatively symbiotic. A few enigmatic bioluminescent symbionts
      have not been successfully cultured, which has led to speculation that they may
      be obligately dependent on their hosts. Here, we report the draft genome of the
      uncultured luminous symbiont of an anomalopid flashlight fish, 'Candidatus
      Photodesmus katoptron'. The genome of the anomalopid symbiont is reduced by 80%
      compared with close relatives and lacks almost all genes necessary for amino acid
      synthesis and for metabolism of energy sources other than glucose, supporting
      obligate dependence on the host for growth. 'Candidatus Photodesmus katoptron' is
      the first described obligate mutualistic symbiont of a vertebrate. Unlike most
      other obligate mutualists, the anomalopid symbiont genome has retained complete
      pathways for chemotaxis and motility as well as most genes involved in cell wall
      production, consistent with the hypothesis that these bacteria may be transmitted
      environmentally during an extra-host phase. 

PMID- 24118865
TI  - Correlates of ADL difficulty in a large hemodialysis cohort.
AB  - Needing assistance with activities of daily living (ADL) is an early indicator of
      functional decline and has important implications for individuals' quality of
      life. However, correlates of need for ADL assistance have received limited
      attention among patients undergoing maintenance hemodialysis (HD). A multicenter
      cohort of 742 prevalent HD patients was assessed in 2009-2011 and classified as
      frail, prefrail and nonfrail by the Fried frailty index (recent unintentional
      weight loss, reported exhaustion, low grip strength, slow walk speed, low
      physical activity). Patients reported need for assistance with 4 ADL tasks and
      identified contributing symptoms/conditions (pain, balance, endurance, weakness,
      others). Nearly 1 in 5 patients needed assistance with 1 or more ADL.
      Multivariable analysis showed increased odds for needing ADL assistance among
      frail (odds ratio [OR] 11.35; 95% confidence interval [CI] 5.50-23.41; P < 0.001)
      and prefrail (OR 1.93; 95% CI 1.01-3.68; P = 0.046) compared with non-frail
      patients. In addition, the odds for needing ADL assistance were lower among
      blacks compared with whites and were higher among patients with diabetes, lung
      disease, and stroke. Balance, weakness, and "other" (frequently dialysis-related)
      symptoms/conditions were the most frequently named reasons for ADL difficulty. In
      addition to interventions such as increasing physical activity that might delay
      or reverse the process of frailty, the immediate symptoms/conditions to which
      individuals attribute their ADL difficulty may have clinical relevance for
      developing targeted management and/or treatment approaches. 

PMID- 24118866
TI  - Temperate mountain grasslands: a climate-herbivore hypothesis for origins and
      persistence.
AB  - Temperate montane grasslands and their unique biotas are declining worldwide as
      they are increasingly being invaded by forests. The origin and persistence of
      these landscapes have been the focus of such controversy that in many areas their
      conservation is in doubt. In the USA some biologists have largely dismissed the
      grass balds of the Southern Appalachians as human artifacts or anomalous and
      transitory elements of regional geography, worthy of only limited preservation
      efforts. On the basis of information from biogeography, community ecology,
      regional history and palaeontology and from consideration of two other montane
      grassland ecosystems-East Carpathian poloninas and Oregon Coast Range grass balds
      we hypothesize that these landscapes are more widespread than was formerly
      recognized; they are, in many cases, natural and ancient and largely owe their
      origin and persistence to past climatic extremes and the activities of large
      mammalian herbivores.

PMID- 24118867
TI  - Decision-making process of prenatal screening described by pregnant women and
      their partners.
AB  - BACKGROUND: Pregnant women are often faced with having to decide about prenatal
      screening for Down's syndrome. However, the decision to participate in or refrain
      from prenatal screening can be seen as an important decision not only for the
      pregnant woman but also for both the partners. OBJECTIVE: The aim of this study
      was to explore the couples' processes of decision making about prenatal
      screening. METHODS: A total of 37 semi-structured interviews conducted at two
      time points were analysed using the interpretive description. SETTING: The study
      was carried out in Maternal health-care centres, Orebro County Council, Sweden.
      PARTICIPANTS: Fifteen couples of different ages and with different experiences of
      pregnancy and childbirth were interviewed. RESULTS: Three different patterns of
      decision making were identified. For the couples in 'The open and communicative
      decision-making process', the process was straightforward and rational, and the
      couples discussed the decision with each other. 'The closed and personal decision
      making process' showed an immediate and non-communicative decision making where
      the couples decided each for themselves. The couples showing 'The searching and
      communicative decision-making process' followed an arduous road in deciding
      whether to participate or not in prenatal screening and how to cope with the
      result. CONCLUSIONS: The decision-making process was for some couples a fairly
      straightforward decision, while for others it was a more complex process that
      required a great deal of consideration.

PMID- 24118868
TI  - Occult hepatitis B virus coinfection in HIV-positive African migrants to the UK:
      a point prevalence study.
AB  - OBJECTIVES: Occult (surface antigen-negative/DNA-positive) hepatitis B virus
      (HBV) infection is common in areas of the world where HBV is endemic. The main
      objectives of this study were to determine the prevalence of occult HBV infection
      in HIV-infected African migrants to the UK and to determine factors associated
      with occult coinfection. METHODS: This anonymized point-prevalence study
      identified Africans attending three HIV clinics, focussing on patients naive to
      antiretroviral therapy (ART). Stored blood samples were tested for HBV DNA.
      Prevalence was calculated in the entire cohort, as well as in subpopulations.
      Risk factors for occult HBV coinfection were identified using logistic regression
      analysis. RESULTS: Among 335 HIV-positive African migrants, the prevalence of
      occult HBV coinfection was 4.5% [95% confidence interval (CI) 2.8-7.4%] overall,
      and 6.5% (95% CI 3.9-10.6%) and 0.8% (95% CI 0.2-4.6%) in ART-naive and ART
      experienced patients, respectively. Among ART-naive anti-HBV core (anti-HBc)
      positive patients, the prevalence was 16.4% (95% CI 8.3-25.6%). The strongest
      predictor of occult coinfection was anti-HBc positivity [odds ratio (OR) 7.4; 95%
      CI 2.0-27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range
      (IQR) 33-513 IU/mL] and 22 U/L (IQR 13-27 U/L), respectively. CONCLUSIONS: Occult
      HBV coinfection remains under-diagnosed in African HIV-infected patients in the
      UK. Given the range of HBV DNA levels observed, further studies are warranted to
      determine its clinical significance and to guide screening strategies and ART
      selection in these patients.

PMID- 24118869
TI  - Is administering blood as useless as blood letting?

PMID- 24118870
TI  - Hematocrit alters VerifyNow P2Y12 assay results independently of intrinsic
      platelet reactivity and clopidogrel responsiveness.
AB  - BACKGROUND: The VerifyNow P2Y12 assay assesses the adequacy of clopidogrel
      therapy by measuring ADP-induced platelet activation in whole blood. Low
      hematocrit is associated with high clopidogrel on-treatment platelet reactivity
      (HTPR) defined by this assay. OBJECTIVES: To characterize the effect of
      hematocrit on VerifyNow values and determine if it is due to hematocrit-dependent
      changes in intrinsic platelet reactivity or an in vitro assay phenomenon.
      PATIENTS/METHODS: Adenosine diphosphate-induced platelet activation was measured
      using the VerifyNow P2Y12 assay, whole blood impedance and light transmission
      platelet aggregometry (LTA) before and after clopidogrel loading in 113 patients
      undergoing elective cardiac catheterization. Iso-TRAP-induced platelet activation
      was additionally measured using the VerifyNow device. Multivariate modeling
      employing clinical and laboratory variables was used to investigate the
      association between hematocrit and VerifyNow values. RESULTS: VerifyNow P2Y12
      reaction units (PRU) and iso-TRAP Base units before and after clopidogrel
      loading, but not their relative change, exhibited strong negative correlation
      with hematocrit (P <= 0.0005 for both). While hematocrit remained a strong
      predictor of post-clopidogrel PRU (P = 0.001) in multivariate modeling, it was
      independent of post-clopidogrel ADP-induced platelet reactivity as measured by
      LTA (P = 0.001). Correcting for the effects of hematocrit resulted in a 15-39%
      reduction in the prevalence of HTPR defined by thresholds of 208-236 PRU.
      CONCLUSIONS: The effect of hematocrit on VerifyNow PRU values is an in vitro
      phenomenon that is independent of intrinsic change in ADP-induced platelet
      reactivity and clopidogrel responsiveness. Correcting for hematocrit when using
      this assay may more accurately identify patients with HTPR that may benefit from
      alternative antiplatelet therapy.

PMID- 24118871
TI  - Predicting cell shapes in melanomas.

PMID- 24118872
TI  - Data processing costs for three posture assessment methods.
AB  - BACKGROUND: Data processing contributes a non-trivial proportion to total
      research costs, but documentation of these costs is rare. This paper employed a
      priori cost tracking for three posture assessment methods (self-report,
      observation of video, and inclinometry), developed a model describing the fixed
      and variable cost components, and simulated additional study scenarios to
      demonstrate the utility of the model. METHODS: Trunk and shoulder postures of
      aircraft baggage handlers were assessed for 80 working days using all three
      methods. A model was developed to estimate data processing phase costs, including
      fixed and variable components related to study planning and administration,
      custom software development, training of analysts, and processing time. RESULTS:
      Observation of video was the most costly data processing method with total cost
      of ? 30,630, and was 1.2-fold more costly than inclinometry (? 26,255), and 2.5
      fold more costly than self-reported data (? 12,491). Simulated scenarios showed
      altering design strategy could substantially impact processing costs. This was
      shown for both fixed parameters, such as software development and training costs,
      and variable parameters, such as the number of work-shift files processed, as
      well as the sampling frequency for video observation. When data collection and
      data processing costs were combined, the cost difference between video and
      inclinometer methods was reduced to 7%; simulated data showed this difference
      could be diminished and, even, reversed at larger study sample sizes. Self-report
      remained substantially less costly under all design strategies, but produced
      alternate exposure metrics. CONCLUSIONS: These findings build on the previously
      published data collection phase cost model by reporting costs for post-collection
      data processing of the same data set. Together, these models permit empirically
      based study planning and identification of cost-efficient study designs.

PMID- 24118874
TI  - Establishment of depression behavioral criteria in cynomolgus monkeys.

PMID- 24118873
TI  - Experience and knowledge of pain management in patients receiving outpatient
      cancer treatment: what do older adults really know about their cancer pain?
AB  - OBJECTIVE: An individual's ability to effectively manage their cancer pain is
      influenced by knowledge and perceptions regarding the pain experience. While
      significance of the physician's knowledge of cancer pain management has been
      reported, much less is known how a patient's knowledge may influence their
      ability to optimally manage their pain. The purpose of this study is to determine
      the influence health and social factors have on the knowledge and experience of
      cancer pain among older adults. DESIGN: A prospective cross-sectional study of
      older Black and White patients presenting for outpatient cancer treatment.
      METHODS: Participants were surveyed on questions assessing pain severity,
      knowledge and experience of pain, self-efficacy for pain treatment, satisfaction
      with pain treatment, and additional social, health, and demographic
      characteristics. A series of hierarchical regression models were specified to
      examine predictors of cancer pain knowledge and experience. RESULTS: Education,
      race, and trust were significant predictors of pain knowledge, whereas self
      efficacy for pain, pain interference, and pain severity were indicators of the
      experience of cancer pain. CONCLUSIONS: Knowledge and experience of (cancer) pain
      are contingent upon a myriad of social and clinical factors that are not
      exclusive but rather coexisting determinants of health. Understanding older
      adults' knowledge of pain may begin to diminish the imparities in the diagnosis
      and treatment of pain among this growing diverse population of older adults. It
      may similarly allow for programs to be tailored to fit the specific needs of the
      patient in the treatment and management of their cancer pain.

PMID- 24118875
TI  - Increased levels of PD-1 expression on CD8 T cells in patients post-renal
      transplant irrespective of chronic high EBV viral load.
AB  - Studies have identified solid organ transplant recipients who remain asymptomatic
      despite maintaining CHL. Factors which determine the CHL state remain poorly
      understood but are likely to involve immunological control of the viral
      infection. We monitored expression of PD-1, a marker of T-cell exhaustion and
      viral persistence, on CD8 T cells in patients who resolved EBV infection as
      determined by undetectable EBV DNA (REI) and CHL patients. PD-1 expression on CD8
      T cells was increased in the first year post-transplant irrespective of EBV
      outcome, and most CD8 T cells continued to express PD-1 for up to three yr post
      transplant. Although all patient groups showed similar frequencies of EBV
      specific CD8+ T cells, PD-1 expression on these cells increased in the post
      transplant groups compared with the pretransplant patients. Functional studies of
      EBV-specific CD8+ T cells stimulated with BZLF or LMP2 peptide pools revealed
      monofunctional IFN-gamma responses. Our results indicate that PD-1 expression on
      CD8 T cells post-transplant may result from factors other than antigenic
      stimulation. 

PMID- 24118876
TI  - Body fatness and breast cancer risk in women of African ancestry.
AB  - BACKGROUND: Obesity has been shown to be inversely associated with breast cancer
      risk in premenopausal women, while increasing risk in postmenopausal women.
      However, the current evidence is largely based on studies in Caucasian
      populations. Associations in women of African ancestry (AA), who have a higher
      prevalence of obesity, have been evaluated in few studies and results suggest
      different effects. METHODS: We evaluated the impact of body size, body fat
      distribution, and body composition on breast cancer risk among AA women (978
      cases and 958 controls) participating in the Women's Circle of Health Study, a
      multi-site case-control study in New York City (NYC) and New Jersey (NJ). Cases
      were newly diagnosed with histologically confirmed ductal carcinoma in situ or
      invasive breast cancer, age 20-75 yrs. In NYC, cases were recruited through
      hospitals with the largest referral patterns for AA women and controls through
      random digit dialing (RDD). In NJ, cases were identified in seven counties in NJ
      thorough the NJ State Cancer Registry, and controls through RDD and community
      based recruitment. During in-person interviews, questionnaires were administered
      and detailed anthropometric measurements were obtained. Body composition was
      assessed by bioelectrical impedance analysis. RESULTS: BMI did not have a major
      impact on pre- or post-menopausal breast cancer, but was significantly associated
      with reduced risk of ER-/PR- tumors among postmenopausal women (OR: 0.37; 95% CI:
      0.15-0.96 for BMI > 30 vs. BMI < 25). Furthermore, increased premenopausal breast
      cancer risk was found for higher waist and hip circumferences after adjusting for
      BMI, with ORs of 2.25 (95% CI: 1.07-4.74) and 2.91 (95% CI: 1.39-6.10),
      respectively, comparing the highest vs. lowest quartile. While ORs for higher fat
      mass and percent body fat among postmenopausal women were above one, confidence
      intervals included the null value. CONCLUSIONS: Our study suggests that in AA
      women BMI is generally unrelated to breast cancer. However, higher waist and hip
      circumferences were associated with increased pre-menopausal breast cancer risk,
      while general obesity was associated with decreased risk of ER-/PR- tumors.
      Larger studies are needed to confirm findings and to evaluate the impact of
      obesity on breast cancer subtypes.

PMID- 24118878
TI  - Jimena: efficient computing and system state identification for genetic
      regulatory networks.
AB  - BACKGROUND: Boolean networks capture switching behavior of many naturally
      occurring regulatory networks. For semi-quantitative modeling, interpolation
      between ON and OFF states is necessary. The high degree polynomial interpolation
      of Boolean genetic regulatory networks (GRNs) in cellular processes such as
      apoptosis or proliferation allows for the modeling of a wider range of node
      interactions than continuous activator-inhibitor models, but suffers from scaling
      problems for networks which contain nodes with more than ~10 inputs. Many GRNs
      from literature or new gene expression experiments exceed those limitations and a
      new approach was developed. RESULTS: (i) As a part of our new GRN simulation
      framework Jimena we introduce and setup Boolean-tree-based data structures; (ii)
      corresponding algorithms greatly expedite the calculation of the polynomial
      interpolation in almost all cases, thereby expanding the range of networks which
      can be simulated by this model in reasonable time. (iii) Stable states for
      discrete models are efficiently counted and identified using binary decision
      diagrams. As application example, we show how system states can now be sampled
      efficiently in small up to large scale hormone disease networks (Arabidopsis
      thaliana development and immunity, pathogen Pseudomonas syringae and modulation
      by cytokinins and plant hormones). CONCLUSIONS: Jimena simulates currently
      available GRNs about 10-100 times faster than the previous implementation of the
      polynomial interpolation model and even greater gains are achieved for large
      scale-free networks. This speed-up also facilitates a much more thorough sampling
      of continuous state spaces which may lead to the identification of new stable
      states. Mutants of large networks can be constructed and analyzed very quickly
      enabling new insights into network robustness and behavior.

PMID- 24118877
TI  - Hydrolysates of glycated and heat-treated peanut 7S globulin (Ara h 1) modulate
      human gut microbial proliferation, survival and adhesion.
AB  - AIMS: Evaluation of an effect of glycation of Ara h 1 on proliferation and
      survival rate and adhesion of intestinal Enterococcus faecalis, Escherichia coli
      and Lactobacillus acidophilus. METHODS AND RESULTS: Pure Ara h 1 heated at three
      different temperature conditions (G37, G60 and C145 degrees C) in the presence or
      absence of glucose was subjected to enzymatic hydrolysis. Impacts of Ara h 1
      hydrolysates on the bacterial proliferation, survival rate and adhesion to Caco-2
      cells in mono and heterogeneous cultures were studied with fluorescent
      techniques: DAPI, LIVE/DEAD staining and FISH. Examined hydrolysates hindered
      proliferation of E. coli and Ent. faecalis with simultaneous decrease in their
      survival. Maillard reaction (MR, glycation) of Ara h 1 did not alter the effect
      of hydrolysates on bacterial proliferation rate. Hydrolysates modified at 60 and
      145 degrees C with glucose altered the profile of immobilized bacteria, mostly by
      lowering the number of adhering E. coli and promoting the adhesion of bacteria
      from genera Lactobacillus and Enterococcus. CONCLUSIONS: Ara h1 hydrolysates
      processed in various ways demonstrated their strong modulatory effect on
      bacterial proliferation, survival rate and adhesion. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Reducing the adhesion of opportunistic bacteria by hydrolysates of Ara
      h 1 glycated at 60 and 145 degrees C, together with modulation of immobilization
      of beneficial lactobacilli and enterococci, may be of relevance in terms of the
      physiological status of the intestinal barrier.

PMID- 24118879
TI  - Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid
      oxidase.
AB  - King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable
      enzyme, is an extremely potent antiproliferative agent against cancer cells when
      compared with LAAO isolated from other snake venoms. King cobra venom LAAO was
      shown to exhibit very strong antiproliferative activities against MCF-7 (human
      breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50
      value of 0.04+/-0.00 and 0.05+/-0.00 MUg/mL, respectively, after 72-hr treatment.
      In comparison, its cytotoxicity was about 3-4 times lower when tested against
      human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting
      selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell
      lines was greater than the effects of doxorubicin, a clinically established
      cancer chemotherapeutic agent, which showed an IC50 value of 0.18+/-0.03 and
      0.63+/-0.21 MUg/mL, respectively, against the two cell lines. The selective
      cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7
      amino-actinomycin (AAD) apoptotic assay, in which a significant increase in
      apoptotic cells was observed in LAAO-treated tumour cells than in their non
      tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour
      cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We
      also determined that this enzyme may target oxidative stress in its killing of
      tumour cells, as its cytotoxicity was significantly reduced in the presence of
      catalase (a H2O2 scavenger). In view of its heat stability and selective and
      potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially
      developed for treating solid tumours.

PMID- 24118880
TI  - IgG4 positive lymphoplasmacytic inflammatory pseudotumour mimicking
      hepatocellular carcinoma.

PMID- 24118881
TI  - Efficacy of sublingual immunotherapy for allergic asthma: retrospective meta
      analysis of randomized, double-blind and placebo-controlled trials.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) is the only available curative
      choice with a disease-modifying effect against respiratory allergies. The
      efficacy of SIT via the sublingual route was demonstrated by a number of clinical
      trials. This meta-analysis was performed to investigate the clinical efficacy and
      safety of sublingual-specific immunotherapy (SLIT) for allergic asthma. METHODS:
      PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were
      searched for randomized, double-blind and placebo-controlled (DBPC) trials
      evaluating the efficacy and safety of SLIT on allergic asthma. Subgroup analyses
      were performed according to age, type of allergen and duration of SLIT treatment.
      RESULTS: Sixteen randomized DBPC trials comprising 794 patients in total met the
      inclusion criteria. The results suggest that SLIT significantly reduces both
      symptom [standardized mean difference (SMD), -0.74; P=0.006] and medication
      scores (SMD, -0.78; P=0.02) compared with placebo. SLIT offers a better clinical
      response in mite sensitive asthmatics but without confirmed proof from subgroup
      analyses. Prolonged duration of treatment for more than 12 months brings no
      additive effects. Improvement in the skin prick test was also observed following
      immunotherapy. There was no consistent effect on forced expiratory volume in 1 s,
      serum levels of antigen-specific immunoglobulin G4 and immunoglobulin E in the
      treated group. The risk of adverse effects was relative risk 2.23 (P=0.01).
      CONCLUSIONS: SLIT is safe and clinically effective in reducing symptoms and
      medication use for allergic asthma. Our subgroup analyses failed to identify a
      disproportionate benefit of SLIT in any specific group of asthmatics, but some
      possible trends did emerge.

PMID- 24118882
TI  - Self-reported quality of sleep is associated with bodily pain, vitality and
      cognitive impairment in Japanese older adults.
AB  - AIM: Poor sleep can affect physical and mental health, and consequently people's
      quality of life (QOL); however, only a few studies have addressed the potential
      associations of physical and mental health with quality of sleep (QOS) in Japan.
      The present study aimed to investigate the association of QOS with
      sociodemographic and lifestyle characteristics, cognitive status, nutrition,
      depression, seclusion, and QOL in Japanese community-dwelling older adults.
      METHODS: Data were collected through self-administered questionnaires and other
      specific tests in 145 (age 73 years [range 70-77 years]) participants. The chi(2)
      -test or Fisher's exact test were used to compare categorical variables
      stratified by QOS, and the Mann-Whitney U-test was used for continuous variables.
      Furthermore, logistic regression analyses were carried out to verify the
      associations with QOS. RESULTS: The poor QOS group had more males (P < 0.05), a
      shorter self-reported sleep duration (P < 0.001), higher body mass index (P <
      0.05) and higher risk of depression (P < 0.05), whereas the good QOS group showed
      higher scores in the QOL summary and domains of physical component (P < 0.01),
      general health (P < 0.001), bodily pain (P < 0.001) and vitality (P < 0.001). In
      the logistic regression model, cognitive status (OR 0.13, 95% CI 0.03-0.55),
      bodily pain (OR 0.91, 95% CI 0.84-1.00) and vitality (OR 0.82, 95% CI 0.73-0.92)
      were associated with QOS. CONCLUSION: The present study provides evidence that
      QOS is linked to cognitive status, bodily pain and vitality in Japanese older
      adults. We maintain that screening a person's sleep characteristics in a
      community setting might be relevant to identify those older adults at risk of a
      poor QOL and frailty in the early phase, triggering further health analyses.

PMID- 24118883
TI  - Disparities in arteriovenous fistula placement in older hemodialysis patients.
AB  - The benefits of an arteriovenous fistula (AVF) as the preferred vascular access
      for hemodialysis have been clearly demonstrated. However, only about 20% of
      patients in the United States initiate hemodialysis with an AVF. In this study,
      we assessed whether disparities exist in the type of first hemodialysis access
      placed prior to dialysis start (rather than that used at dialysis initiation), to
      detect whether certain disadvantaged groups might have lower likelihood of AVF
      placement. Study cohort of 118,767 incident hemodialysis patients >=67 years of
      age (1/2005-12/2008) derived from the United States Renal Data System was linked
      with Medicare claims data to identify the type of initial access placed
      predialysis. We used logistic regression model with outcome being the initial
      predialysis placement of an AVF as opposed to an arteriovenous graft or a central
      venous catheter. Increasing age, female sex, black race, lower body mass index,
      urban location, certain comorbidities, and shorter pre-end-stage renal disease
      nephrology care are all associated with a significantly lower likelihood of AVF
      placement as initial access predialysis. Our study suggests the presence of
      significant disparities in the placement of an AVF as initial hemodialysis
      vascular access. We suggest that additional attention should be paid to these
      patient groups to improve disparities by patient education, earlier referral, and
      close follow-up. 

PMID- 24118884
TI  - Emergencies in radiology: a survey of radiologists and radiology trainees.
AB  - INTRODUCTION: Emergencies in radiology are infrequent but potentially lethal.
      Australian and New Zealand radiologists are advised to undergo resuscitation
      training at least every three years; however, little is known about their
      experience and confidence in managing common emergencies relevant to their
      clinical practice. This paper describes the current experience and confidence of
      radiologists and radiology trainees in Australia and New Zealand in the
      management of common medical emergencies. METHODS: A cross-sectional online
      survey of trainees and fellows of the Royal Australian and New Zealand College of
      Radiology collected data on training and learning preferences relating to
      resuscitation and life-support skills, access to emergency medical care, and
      knowledge, confidence and ability in managing a variety of medical emergencies.
      RESULTS: There were 602 responses to the survey (response rate 23.4%). The
      majority of respondents were interested in learning more about the management of
      contrast reactions, cardiac arrest, ischaemic chest pain and basic life support.
      Self-rated knowledge, confidence and ability were higher in respondents who had
      completed life-support training within the previous three years. In this group,
      however, more than 40% rated their ability at managing contrast reactions as poor
      or fair, while more than 60% rated their ability as poor or fair for management
      of cardiac arrest, basic life support, advanced life support and dosing of
      adrenaline. Preferred resuscitation training modalities included simulation,
      small-group tutorials and workshops. CONCLUSION: Self-reported level of skill and
      expertise in the management of potential emergencies in radiology is suboptimal
      among a large number of respondents. Consideration should be given to addressing
      this by improving access to specific training.

PMID- 24118885
TI  - Diacylglycerol acyltransferase 1 inhibition with AZD7687 alters lipid handling
      and hormone secretion in the gut with intolerable side effects: a randomized
      clinical trial.
AB  - AIM: Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is a potential
      treatment modality for patients with type 2 diabetes mellitus and obesity, based
      on preclinical data suggesting it is associated with insulin sensitization and
      weight loss. This randomized, placebo-controlled, phase 1 study in 62 overweight
      or obese men explored the effects and tolerability of AZD7687, a reversible and
      selective DGAT1 inhibitor. METHODS: Multiple doses of AZD7687 (1, 2.5, 5, 10 and
      20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1
      week. Postprandial serum triacylglycerol (TAG) was measured for 8 h after a
      standardized 45% fat meal. Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)
      were measured and a paracetamol challenge was performed to assess gastric
      emptying. RESULTS: Dose-dependent reductions in postprandial serum TAG were
      demonstrated with AZD7687 doses >=5 mg compared with placebo (p < 0.01).
      Significant (p < 0.001) increases in plasma GLP-1 and PYY levels were seen at
      these doses, but no clear effect on gastric emptying was demonstrated at the end
      of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects
      increased; 11/18 of these participants discontinued treatment owing to diarrhoea.
      CONCLUSIONS: Altered lipid handling and hormone secretion in the gut were
      demonstrated during 1-week treatment with the DGAT1 inhibitor AZD7687. However,
      the apparent lack of therapeutic window owing to GI side effects of AZD7687,
      particularly diarrhoea, makes the utility of DGAT1 inhibition as a novel
      treatment for diabetes and obesity questionable.

PMID- 24118886
TI  - Identification and biochemical characterization of the novel mutation m.8839G>C
      in the mitochondrial ATP6 gene associated with NARP syndrome.
AB  - Mutations in the ATP6 gene are reported to be associated with Leber hereditary
      optic neuropathy, bilateral striatal necrosis, coronary atherosclerosis risk and
      neuropathy, ataxia and retinitis pigmentosa (NARP)/maternally inherited Leigh
      syndromes. Here, we present a patient with NARP syndrome, in whom a previously
      undescribed mutation was detected in the ATP6 gene: m.8839G>C. Several
      observations support the concept that m.8839G>C is pathogenically involved in the
      clinical phenotype of this patient: (1) the mutation was heteroplasmic in muscle;
      (2) mutation load was higher in the symptomatic patient than in the asymptomatic
      carriers; (3) cybrids carrying this mutation presented lower cell proliferation,
      increased mitochondrial DNA (mtDNA) copy number, increased steady-state OxPhos
      protein levels and decreased mitochondrial membrane potential with respect to
      isogenic wild-type cybrids; (4) this change was not observed in 2959 human mtDNAs
      from different mitochondrial haplogroups; (5) the affected amino acid was
      conserved in all the ATP6 sequences analyzed; and (6) using in silico prediction,
      the mutation was classified as 'probably damaging'. However, measurement of ATP
      synthesis showed no differences between wild-type and mutated cybrids. Thus, we
      suggest that m.8839G>C may lower the efficiency between proton translocation
      within F0 and F1 rotation, required for ATP synthesis. Further experiments are
      needed to fully characterize the molecular mechanisms involved in m.8839G>C
      pathogenicity.

PMID- 24118887
TI  - Stromatolitic knobs in Storr's Lake (San Salvador, Bahamas): a model system for
      formation and alteration of laminae.
AB  - The initial lamination in young, metabolically active Scytonema knobs developing
      in Storr's Lake (Bahamas) results from the iterative succession of two different
      stages of microbial growth at the top of this microbialite. Stage 1 is dominated
      by vertically oriented cyanobacterial filaments and is characterized by a high
      porosity of the fabric. Stage 2 shows a higher microbial density with the
      filaments oriented horizontally and with higher carbonate content. The more
      developed, dense microbial community associated with Stage 2 of the Scytonema
      knobs rapidly degrades extracellular organic matter (EOM) and coupled to this,
      precipitates carbonate. The initial nucleation forms high-Mg calcite
      nanospheroids that progressively replace the EOM. No precipitation is observed
      within the thick sheath of the Scytonema filaments, possibly because of strong
      cross-linking of calcium and EOM (forming EOM-Ca-EOM complexes), which renders Ca
      unavailable for carbonate nucleation (inhibition process). Eventually,
      organominerals precipitate and form an initial lamina through physicochemical and
      microbial processes, including high rates of photosynthetic activity that lead to
      (13) C-enriched DIC available for initial nucleation. As this lamina moves
      downward by the iterative production of new laminae at the top of the
      microbialite, increased heterotrophic activity further alters the initial mineral
      product at depth. Although some rare relic preservation of 'Stage 1-Stage 2'
      laminae in subfossil knobs exists, the very fine primary lamination is
      considerably altered and almost completely lost when the knobs develop into
      larger and more complex morphologies due to the increased accommodation space and
      related physicochemical and/or biological alteration. Despite considerable
      differences in microstructure, the emerging ecological model of community
      succession leading to laminae formation described here for the Scytonema knobs
      can be applied to the formation of coarse-grained, open marine stromatolites.
      Therefore, both fine- and coarse-grained extant stromatolites can be used as
      model systems to understand the formation of microbialites in the fossil record. 

PMID- 24118888
TI  - Record of archaeal activity at the serpentinite-hosted Lost City Hydrothermal
      Field.
AB  - Samples of young, outer surfaces of brucite-carbonate deposits from the
      ultramafic-hosted Lost City hydrothermal field were analyzed for DNA and lipid
      biomarker distributions and for carbon and hydrogen stable isotope compositions
      of the lipids. Methane-cycling archaeal communities, notably the Lost City
      Methanosarcinales (LCMS) phylotype, are specifically addressed. Lost City is
      unlike all other hydrothermal systems known to date and is characterized by metal
      and CO2 -poor, high pH fluids with high H2 and CH4 contents resulting from
      serpentinization processes at depth. The archaeal fraction of the microbial
      community varies widely within the Lost City chimneys, from 1-81% and covaries
      with concentrations of hydrogen within the fluids. Archaeal lipids include
      isoprenoid glycerol di- and tetraethers and C25 and C30 isoprenoid hydrocarbons
      (pentamethylicosane derivatives - PMIs - and squalenoids). In particular,
      unsaturated PMIs and squalenoids, attributed to the LCMS archaea, were identified
      for the first time in the carbonate deposits at Lost City and probably record
      processes exclusively occurring at the surface of the chimneys. The carbon
      isotope compositions of PMIs and squalenoids are remarkably heterogeneous across
      samples and show highly (13) C-enriched signatures reaching delta(13) C values of
      up to +24.60/00. Unlike other environments in which similar structural and
      isotopic lipid heterogeneity has been observed and attributed to diversity in the
      archaeal assemblage, the lipids here appear to be synthesized solely by the LCMS.
      Some of the variations in lipid isotope signatures may, in part, be due to
      unusual isotopic fractionation during biosynthesis under extreme conditions.
      However, we argue that the diversity in archaeal abundances, lipid structure and
      carbon isotope composition rather reflects the ability of the LCMS archaeal
      biofilms to adapt to chemical gradients in the hydrothermal chimneys and possibly
      to perform either methanotrophy or methanogenesis using dissolved inorganic
      carbon, methane or formate as a function of the prevailing environmental
      conditions. 

PMID- 24118889
TI  - Impact of GB virus C viraemia on clinical outcome in HIV-1-infected patients: a
      20-year follow-up study.
AB  - OBJECTIVES: The impact of coexisting GB virus C (GBV-C) infection on the clinical
      course of HIV infection remains controversial. Early data from HIV-1 infected
      patients attending the Hannover Medical School in 2001 suggested prognostic
      benefit in GBV-C viraemic patients. The aim of this study was to evaluate
      patterns in long-term mortality and morbidity outcomes in this cohort. The impact
      of the introduction of antiretroviral therapy (ART) on the perceived benefits of
      GBV-C viraemia was subsequently investigated. METHODS: A retrospective follow-up
      analysis of data in this cohort was performed. GBV-C status (GBV-C RNA positive,
      antibodies against GBV-C envelope protein E2 or no evidence of GBV-C exposure)
      had been determined at enrolment, with several markers of HIV disease progression
      (such as viral load and CD4 cell count) being collated from 1993/1994, 2000 and
      2012. These eras were chosen to reflect variations in treatment strategies within
      the cohort. In addition, mortality and HIV-related morbidity data were collated
      for all patients. RESULTS: Complete data were available for 156 of 197 patients
      (79%). In highly active antiretroviral therapy (HAART)-naive patients, GBV-C RNA
      positivity conferred significant improvements in the course of HIV infection and
      mortality as well as lower rates of HIV-related diseases. E2 positivity alone
      conferred no significant advantage. With the advent of HAART, however, the
      benefits GBV-C RNA positivity disappeared. CONCLUSIONS: Although GBV-C
      coinfection appears to inherently improve morbidity and mortality in HIV-infected
      patients, modern HAART has eradicated these advantages. Evidence of synergy
      between GBV-C status and HAART response exists, with further studies examining
      the role of GBV-C in existing treatment de-escalation strategies being required.

PMID- 24118890
TI  - Shotgun proteomics suggests involvement of additional enzymes in dioxin
      degradation by Sphingomonas wittichii RW1.
AB  - Chlorinated congeners of dibenzo-p-dioxin and dibenzofuran are widely dispersed
      pollutants that can be treated using microorganisms, such as the Sphingomonas
      wittichii RW1 bacterium, able to transform some of them into non-toxic
      substances. The enzymes of the upper pathway for dibenzo-p-dioxin degradation in
      S. wittichii RW1 have been biochemically and genetically characterized, but its
      genome sequence indicated the existence of a tremendous potential for aromatic
      compound transformation, with 56 ring-hydroxylating dioxygenase subunits, 34
      extradiol dioxygenases and 40 hydrolases. To further characterize this enzymatic
      arsenal, new methodological approaches should be employed. Here, a large shotgun
      proteomic survey was performed on cells grown on dibenzofuran, dibenzo-p-dioxin
      and 2-chlorodibenzo-p-dioxin, and compared with growth on acetate. Changes in the
      proteome were monitored over time. In total, 502 proteins were observed and
      quantified using a label-free mass spectrometry-based approach; all data were
      deposited to the ProteomeXchange (PXD000403). Our results confirmed the roles of
      the dioxin dioxygenase DxnA1A2, trihydroxybiphenyl dioxygenase DbfB, meta
      cleavage product hydrolase DxnB and reductase RedA2, and corroborated the
      proposed involvement of the Swit_3046 dioxygenase and DxnB2 hydrolase. Trends
      across substrates and over the course of growth do not support concerted pathway
      regulation and suggest the involvement of an additional hydrolase and several
      TonB-dependent receptors.

PMID- 24118891
TI  - Patients' views of teamwork in the emergency department offer insights about team
      performance.
AB  - BACKGROUND: Research into efforts to engage patients in the assessment of health
      care teams is limited. OBJECTIVE: To explore, through qualitative methods,
      patient awareness of teamwork-related behaviours observed during an emergency
      department (ED) visit. DESIGN: Researchers used semi-structured question guides
      for audio-recorded interviews and analysed their verbatim transcripts. SETTING
      AND PARTICIPANTS: Researchers conducted individual phone interviews with 6
      teamwork subject matter experts (SMEs) and held 5 face-to-face group interviews
      with patients and caregivers (n = 25) about 2 weeks after discharge from the
      emergency department (ED). RESULTS: SMEs suggested that a range of factors
      influence patient perspectives of teams. Many patients perceived the health-care
      team within the context of their expectations of an ED visit and their treatment
      plan. Four themes emerged: (i) patient-centred views highlight gaps in
      coordination and communication; (ii) team processes do concern patients; (iii)
      patients are critical observers of ways that team members present their team
      roles; (iv) patients' observations of team members relate to patients' views of
      team effectiveness. Analysis also indicated that patients viewed health-care team
      members' interactions with each other as proxy for how team members actually felt
      about patients. DISCUSSION: Results from both sets of interviews (SME and
      patient) indicated that patient observations of teamwork could add to assessment
      of team processes/frameworks. Patients' understanding about teamwork organization
      seemed helpful and witnessed interteam communication appeared to influence
      patient confidence in the team. CONCLUSION: Patients perspectives are an
      important part of assessment in health care and suggest potential areas for
      improvement through team training.

PMID- 24118892
TI  - Peptic ulcer bleeding in China: a multicenter endoscopic survey of 1006 patients.
AB  - OBJECTIVE: We aimed to describe the clinical picture, management and outcomes of
      Chinese patients with peptic ulcer bleeding (PUB), especially in those with high
      risks. METHODS: A multicenter endoscopic survey was conducted. All consecutive
      patients with endoscopy confirmed PUB from October 2010 to June 2011 were
      enrolled. Data including patients' gender, age, symptoms and endoscopic findings,
      Forrest classification, and endoscopic and medical treatment were documented.
      High-risk ulcer was defined as Forrest grades Ia to IIb upon endoscopy. Rates of
      rebleeding, surgery and mortality were recorded. RESULTS: In all, 1006 patients
      were included. Of these 437 (43.4%) were categorized with high-risk PUB, among
      whom 110 (25.2%) received endoscopic treatment, and the success rate was 99.1%.
      Rebleeding rates 1-3 days, 4-5 days and 6-30 days after treatment in high-risk
      patients who did and did not receive endoscopic treatment were 10.9% versus
      10.4%, 3.6% versus 3.7% and 0.9% versus 1.5%, respectively. The surgery rates of
      high-risk patients with or without endoscopic treatment were 1.8% (2/110) versus
      1.8% (6/327). During the 9-month study period, two patients with high-risk PUB
      died, therefore, the overall mortality rate of high-risk PUB was 0.5% (2/437).
      CONCLUSION: The study suggests that the proportions of high-risk PUB in China is
      43.4%, while rebleeding and surgery rate after endoscopic treatment as well as
      the mortality rate of high-risk PUB in China are 15.6%, 1.8% and 0.5%,
      respectively.

PMID- 24118893
TI  - The Crc protein inhibits the production of polyhydroxyalkanoates in Pseudomonas
      putida under balanced carbon/nitrogen growth conditions.
AB  - Pseudomonas putida synthesizes polyhydroxyalkanoates (PHAs) as storage compounds.
      PHA synthesis is more active when the carbon source is in excess and the nitrogen
      source is limiting, but can also occur at a lower rate under balanced
      carbon/nitrogen ratios. This work shows that PHA synthesis is controlled by the
      Crc global regulator, a protein that optimizes carbon metabolism by inhibiting
      the expression of genes involved in the use of non-preferred carbon sources. Crc
      acts post-transcriptionally. The mRNAs of target genes contain characteristic
      catabolite activity (CA) motifs near the ribosome binding site. Sequences
      resembling CA motifs can be predicted for the phaC1 gene, which codes for a PHA
      polymerase, and for phaI and phaF, which encode proteins associated to PHA
      granules. Our results show that Crc inhibits the translation of phaC1 mRNA, but
      not that of phaI or phaF, reducing the amount of PHA accumulated in the cell. Crc
      inhibited PHA synthesis during exponential growth in media containing a balanced
      carbon/nitrogen ratio. No inhibition was seen when the carbon/nitrogen ratio was
      imbalanced. This extends the role of Crc beyond that of controlling the
      hierarchical utilization of carbon sources and provides a link between PHA
      synthesis and the global regulatory networks controlling carbon flow.

PMID- 24118894
TI  - Radicular maturity level of primary teeth and its association with trauma
      sequelae.
AB  - AIM: This study aimed to investigate the influence of the radicular maturity
      level of primary teeth on the sequelae of traumatic dental injury (TDI).
      MATERIALS AND METHODS: A longitudinal retrospective study that collected data
      from dental records and radiographs of patients with TDI in one or both maxillary
      primary central incisors was conducted. Sequelae such as crown discoloration,
      pulp canal obliteration (PCO) and inflammatory root resorption (IRR) were
      evaluated during a 12- to 18-month follow-up period after the trauma. RESULTS: Of
      the 132 patients included in the study, 103 (78%) had luxations and 29 (22%) had
      dental fractures. At the initial postinjury examination, 12 teeth (9.1%) were
      found to have immature roots, 107 (81.1%) had closed apexes and 13 (9.8%) had
      visible root resorption. Inflammatory root resorption occurred mostly in
      traumatized teeth that presented with physiological root resorption at the moment
      of trauma (P = 0.004). The frequency of PCO was higher in teeth with a closed
      apex at the moment of the injury (P = 0.026). There was also an association
      between the type of injury and the occurrence of crown discoloration (P = 0.008)
      as well as between the type of injury and the development of PCO (P = 0.001).
      CONCLUSIONS: The occurrence of TDI sequelae can be determined by the type of
      injury as well as by the radicular maturity level of the primary teeth at the
      moment of injury.

PMID- 24118895
TI  - Thermal imaging comparison of Signature, Infiniti, and Stellaris
      phacoemulsification systems.
AB  - BACKGROUND: To compare the heat production of 3 different phacoemulsification
      machines under strict laboratory test conditions. More specifically, the thermal
      behavior was analyzed between the torsional modality of the Infiniti system and
      longitudinal modalities of the Abbot WhiteStar Signature Phacoemulsification
      system and Bausch and Lomb Stellaris system. METHODS: Experiments were performed
      under in-vitro conditions in this study.Three phacoemulsification handpieces
      (Infiniti, Signature, and Stellaris) were inserted into balanced salt solution
      filled silicone test chambers and were imaged side-by-side by using a thermal
      camera. Incision compression was simulated by suspending 30.66-gram weights from
      the silicone chambers. The irrigation flow rate was set at 0, 1, 2, 3, 4, and 5
      cc/min and the phacoemulsification power on the instrument consoles was set at
      40, 60, 80, and 100%. The highest temperatures generated from each handpiece
      around the point of compression were measured at 0, 10, 30, and 60 seconds.
      RESULTS: Under the same displayed phacoemulsification power settings, the peak
      temperatures measured when using the Infiniti were lower than when using the
      other two machines, and the Signature was cooler than the Stellaris. At 10
      seconds, torsional phacoemulsification with Infiniti at 100% power showed data
      comparable to that of the Signature at 80% and the Stellaris at 60%. At 30
      seconds, the temperature from the Infiniti at 100% power was lower than the
      Signature at 60% and the Stellaris at 40%. CONCLUSIONS: Torsional
      phacoemulsification with the Infiniti generates less heat than longitudinal
      phacoemulsification with the Signature and the Stellaris. Lower operating
      temperatures indicate lower heat generation within the same fluid volume, which
      may provide additional thermal protection during cataract surgery.

PMID- 24118897
TI  - Acute hepatitis and acute kidney insufficiency caused by ingestion of raw grass
      carp gall bladder.

PMID- 24118896
TI  - Depression prevalence and primary care among vulnerable patients at a free
      outpatient clinic in Paris, France, in 2010: results of a cross-sectional survey.
AB  - BACKGROUND: Data on the prevalence of depression and on how a depressive episode
      prompts the sufferer to seek primary care are not scarce, but the available
      evidence on the prevalence of depression among immigrants and poor people who
      frequent general practice facilities is scarce. The Baudelaire Outpatient Clinic
      at the Saint-Antoine Hospital in Paris provides free medical and social
      assistance to the poor and/or uninsured. The goal of our study was to estimate
      the prevalence of depression among these outpatients, to characterize this
      depressed population, and to analyze its demand for primary care for depressive
      episodes. METHODS: From September to December 2010, we conducted a cross
      sectional, observational survey among users of the Baudelaire Outpatient Clinic.
      French-speaking patients attending the clinic between September 15 and December
      30, 2010 who agreed to answer a questionnaire administered face-to-face before
      their consultation were included in the study. The chi-squared test (or Fisher's
      exact test for small samples) was used for the comparisons of proportions.
      Logistic regression models were estimated, along with the odds ratios (OR) and
      their 95% confidence intervals (95% CIs), for the multivariate analysis of
      factors associated with depression and healthcare-seeking. Models were estimated
      separately for men and women, since sex was an interaction factor. The
      statistical analyses were performed using Stata v. 10 software (StataCorp LP,
      College Station, Texas, USA). RESULTS: Of the 250 patients included (mean age: 45
      years), 52.0% were men and 52.4% were immigrants. Close to 40% of them reported
      having no supplemental health insurance. The estimated prevalence of depression
      in this population was 56.7%. Depression was more prevalent among the women,
      immigrants, and people from the poorer socioeconomic groups. Only half of these
      depressed patients, mostly women, reported having discussed their depression with
      a physician. French nationality and complete health insurance coverage were
      associated with more-frequent healthcare-seeking. Few patients reported having
      been asked about their morale by the physician they consulted, and almost 80%
      would have liked to be asked about this more often. CONCLUSION: Depression is a
      real public health problem, particularly among people from disadvantaged
      backgrounds, and should be included in their overall management.

PMID- 24118898
TI  - Basiliximab with delayed introduction of calcineurin inhibitors as a renal
      sparing protocol following liver transplantation in children with renal
      impairment.
AB  - Renal impairment is frequently compromised in patients with end-stage liver
      disease and is associated with increased long-term mortality post-LT. In contrast
      to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic
      potential. This study reviews the experience of a single pediatric liver
      transplant center's renal-sparing approach with the use of basiliximab and MMF to
      compensate for delayed entry of CNI in children with renal impairment at the time
      of organ availability. There were no differences in renal function between
      pediatric patients with and without pre-LT renal impairment within the first year
      (cGFR: 135 mL/min/1.73 m2 vs. 144 mL/min/1.73 m2 ; p = 0.56) or at 5-8 yr
      following LT, (129 mL/min/1.73 m2 vs. 130 mL/min/1.73 m2 ; p = 0.97). In
      addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between
      patients in the basiliximab group and those patients receiving standard CNI and
      steroid strategies. The utilization of a renal-sparing approach with basiliximab
      alongside delayed entry and lower early target trough levels of CNI in children
      with renal impairment at the time of LT is safe and maintains excellent long-term
      kidney function.

PMID- 24118899
TI  - Human liver sinusoidal endothelial cells but not hepatocytes contain factor VIII.
AB  - BACKGROUND: Although the liver is the major site of coagulation factor VIII
      (FVIII) synthesis, the type of cells producing FVIII within the liver is still
      unclear. OBJECTIVES: To measure FVIII in extracts of primary liver sinusoidal
      endothelial cells (LSECs) and hepatocytes, thereby preventing potential bias
      resulting from the modifications of the cell phenotype that can take place during
      in vitro culture. METHODS: LSECs were purified by flow cytometry cell sorting on
      the basis of their coexpression of Tie2 and CD32b. The purity of the cells was
      controlled by RNA sequencing. FVIII activity (FVIII:C) in extracts of purified
      cells was measured with a sensitive FVIII chromogenic assay, in which the
      specificity of the reaction is controlled by neutralization of FVIII activity
      with specific inhibitor antibodies. RESULTS: The FVIII:C concentration in
      purified LSECs ranged from 0.3 to 2.8 nU per cell. In contrast, FVIII:C was
      undetectable in hepatocytes. The intracellular FVIII:C concentrations are
      therefore at least 10-100-fold higher in LSECs than in hepatocytes. CONCLUSIONS:
      Our data demonstrate that LSECs, but not hepatocytes, contain measurable amounts
      of FVIII:C, and suggest that the former are the main cells producing FVIII in the
      human liver.

PMID- 24118900
TI  - An improvement of mechanical pain sensitivity measurement method: the smaller
      sized probes may detect heterogeneous sensory threshold in healthy male subjects.
AB  - OBJECTIVE: On the basis of our experience in the application of the mechanical
      algometer and a number of pilot experiments, we speculated that 0.1- and 0.01
      cm(2) probes might improve the measurement of mechanical pain sensitivity
      relative to the conventional 1-cm(2) probe. Here, we examined the accuracy,
      feasibility, and applicability of these probes in detecting the mechanical pain
      sensitivity. DESIGN: Mechanical pain threshold and tolerance tests were performed
      on subjects using the three probes of 1, 0.1, and 0.01 cm(2) in random order. We
      compared the application of these probes. SETTING: The study was set at the
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan,
      China. SUBJECTS: Fifty healthy male Han Chinese subjects were recruited. OUTCOME
      MEASURES: We compared the qualities of stimulus-evoked pain, test stability, the
      measuring time, the subjects' acceptance level of the procedure, the validity of
      pain measurement, and the arduousness of the task for the investigator among the
      three different size probes. RESULTS: Compared with the conventional 1-cm(2)
      probe, the 0.01- and 0.1-cm(2) probes resulted in the subjects responding to
      stimulus-evoked pain more quickly, accurately, and consistently, and also made
      the measurement more comfortable for investigators. Up to 80% of the subjects
      reported the pain quality as a pricking sensation when the 0.01-cm(2) probe was
      used. CONCLUSION: The use of the 0.1-cm(2) probe might be more suitable as an
      optimized method for the detection of pressure pain sensitivity in clinical
      studies. In addition, the 0.01-cm(2) probe could potentially serve as an
      alternative to the weighted needle pinprick, providing continuous quantizing
      detection for pricking pain sensitivity.

PMID- 24118901
TI  - Fishful thinking: the rise and fall of MITF in melanoma.

PMID- 24118902
TI  - Role of platelets in inflammation and cancer: novel therapeutic strategies.
AB  - Platelets play a central role in inflammation through their direct interaction
      with other cell types, such as leucocytes and endothelial cells, and by the
      release of many factors, that is, lipids [such as thromboxane (TX)A2 ] and
      proteins (a wide number of angiogenic and growth factors) stored in alpha
      granules, and adenosine diphosphate (ADP), stored in dense granules. These
      platelet actions trigger autocrine and paracrine activation processes that lead
      to leucocyte recruitment into different tissues and phenotypic changes in stromal
      cells which contribute to the development of different disease states, such as
      atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The
      signals induced by platelets may cause pro-inflammatory and malignant phenotypes
      in other cells through the persistent induction of aberrant expression of
      cyclooxygenase (COX)-2 and increased generation of prostanoids, mainly
      prostaglandin (PG)E2 . In addition to cardiovascular disease, enhanced platelet
      activation has been detected in inflammatory disease and intestinal
      tumourigenesis. Moreover, the results of clinical studies have shown that the
      antiplatelet drug aspirin reduces the incidence of vascular events and colorectal
      cancer. All these pieces of evidence support the notion that colorectal cancer
      and atherothrombosis may share a common mechanism of disease, that is, platelet
      activation in response to epithelial (in tumourigenesis) and endothelial (in
      tumourigenesis and atherothrombosis) injury. Extensive translational medicine
      research is necessary to obtain a definitive mechanistic demonstration of the
      platelet-mediated hypothesis of colon tumourigenesis. The results of these
      studies will be fundamental to support the clinical decision to recommend the use
      of low-dose aspirin, and possibly other antiplatelet agents, in primary
      prevention, that is, even for individuals at low cardiovascular risk. 

PMID- 24118903
TI  - Confronting inconsistencies in the amphibian-chytridiomycosis system:
      implications for disease management.
AB  - Chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis
      (Bd), is one of the largest threats to wildlife and is putatively linked to the
      extirpation of numerous amphibians. Despite over a decade of research on Bd,
      conflicting results from a number of studies make it difficult to forecast where
      future epizootics will occur and how to manage this pathogen effectively. Here,
      we emphasize how resolving these conflicts will advance Bd management and
      amphibian conservation efforts. We synthesize current knowledge on whether Bd is
      novel or endemic, whether amphibians exhibit acquired resistance to Bd, the
      importance of host resistance versus tolerance to Bd, and how biotic (e.g.
      species richness) and abiotic factors (e.g. climate change) affect Bd abundance.
      Advances in our knowledge of amphibian-chytrid interactions might inform the
      management of fungal pathogens in general, which are becoming more common and
      problematic globally.

PMID- 24118904
TI  - Modeling the next generation sequencing sample processing pipeline for the
      purposes of classification.
AB  - BACKGROUND: A key goal of systems biology and translational genomics is to
      utilize high-throughput measurements of cellular states to develop expression
      based classifiers for discriminating among different phenotypes. Recent
      developments of Next Generation Sequencing (NGS) technologies can facilitate
      classifier design by providing expression measurements for tens of thousands of
      genes simultaneously via the abundance of their mRNA transcripts. Because NGS
      technologies result in a nonlinear transformation of the actual expression
      distributions, their application can result in data that are less discriminative
      than would be the actual expression levels themselves, were they directly
      observable. RESULTS: Using state-of-the-art distributional modeling for the NGS
      processing pipeline, this paper studies how that pipeline, via the resulting
      nonlinear transformation, affects classification and feature selection. The
      effects of different factors are considered and NGS-based classification is
      compared to SAGE-based classification and classification directly on the raw
      expression data, which is represented by a very high-dimensional model previously
      developed for gene expression. As expected, the nonlinear transformation
      resulting from NGS processing diminishes classification accuracy; however, owing
      to a larger number of reads, NGS-based classification outperforms SAGE-based
      classification. CONCLUSIONS: Having high numbers of reads can mitigate the
      degradation in classification performance resulting from the effects of NGS
      technologies. Hence, when performing a RNA-Seq analysis, using the highest
      possible coverage of the genome is recommended for the purposes of
      classification.

PMID- 24118905
TI  - Combining statins with tissue plasminogen activator treatment after experimental
      and human stroke: a safety study on hemorrhagic transformation.
AB  - AIMS: Statins may afford neuroprotection against ischemic injury, but it remains
      controversial whether combined treatment with tissue plasminogen activator (tPA)
      after stroke increases the risk of hemorrhagic transformation (HT), the major tPA
      related complication. We evaluated the safety of combining statin with tPA
      administration during the acute phase of both experimental and human stroke.
      METHODS: The occurrence and severity of HT, infarct volume, and neurological
      outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to
      embolic middle cerebral arterial occlusion (MCAO), which received vehicle or
      simvastatin (20 mg/kg), 15 min after ischemia and tPA (9 mg/kg) 3 h after
      ischemia. Additionally, HT rate was evaluated in stroke patients who were treated
      with tPA (0.9 mg/kg) within 3 h after symptom onset, considering whether or not
      were under statins treatment when the stroke occurred. RESULTS: In the
      experimental study, no differences in HT rates and severity were found between
      treatment groups, neither regarding mortality, neurological deficit, infarct
      volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT
      rates and hemorrhage type were similar in stroke patients who were or not under
      statins treatment. CONCLUSION: This study consistently confirms that the use of
      statins does not increase HT rates and severity when is combined with tPA
      administration.

PMID- 24118906
TI  - The evaluation of efficacy and safety of sunitinib on EGFR-TKI pretreated
      advanced non-small cell lung cancer patients in China.
AB  - BACKGROUND: Sunitinib is an oral multitargeted tyrosine kinase inhibitor (TKI)
      exhibiting antiagiogenic and antitumor effects. OBJECTIVE: To evaluate the
      efficacy and potential toxicity of sunitinib therapy in advanced non-small cell
      lung cancer (NSCLC) patients in China. METHODS: From January 2009 to August 2011,
      30 patients with stage IV NSCLC, who were pretreated with the epidermal growth
      factor receptor (EGFR)-TKIs and then received sunitinib, were retrospectively
      reviewed. Univariate and multivariate Cox proportional hazard regression analysis
      was performed to determine the potential prognostic risk factors influencing
      NSCLC survival. RESULTS: The median progression-free survival (PFS) and median
      overall survival (OS) of all 30 treated patients was 1.25 months [95% confidence
      interval (CI): 0.90-1.9 months] and 3.40 months (95% CI: 3.00-6.80 months),
      respectively. Cox regression analysis suggested that Eastern Cooperative Oncology
      Group (ECOG) performance status (PS) is predictive of both PFS (P=0.001) and OS
      (P<0.001). Common adverse events (AEs) included hand-foot syndrome (53.3%),
      mucositis (40.0%), rash (36.7%) and diarrhea (33.3%). CONCLUSION: No sign of
      overall clinical benefits of sunitinib was detected in patients with pretreated
      EGFR-TKIs. Most patients suffered AEs from mild to moderate severity. ECOG PS is
      highly associated with PFS and OS rate. Further studies in NSCLC are required to
      determine whether sunitinib is beneficial nor not.

PMID- 24118907
TI  - Biofilm formation and antibiotic production in Ruegeria mobilis are influenced by
      intracellular concentrations of cyclic dimeric guanosinmonophosphate.
AB  - In many species of the marine Roseobacter clade, periods of attached life, in
      association with phytoplankton or particles, are interspersed with planktonic
      phases. The purpose of this study was to determine whether shifts between motile
      and sessile life in the globally abundant Roseobacter clade species Ruegeria
      mobilis are associated with intracellular concentrations of the signal compound
      cyclic dimeric guanosinmonophosphate (c-di-GMP), which in bacteria regulates
      transitions between motile and sessile life stages. Genes for diguanylate
      cyclases and phosphodiesterases, which are involved in c-di-GMP signalling, were
      found in the genome of R. mobilis strain F1926. Ion pair chromatography-tandem
      mass spectrometry revealed 20-fold higher c-di-GMP concentrations per cell in
      biofilm-containing cultures than in planktonic cells. An introduced diguanylate
      cyclase gene increased c-di-GMP and enhanced biofilm formation and production of
      the potent antibiotic tropodithietic acid (TDA). An introduced phosphodiesterase
      gene decreased c-di-GMP and reduced biofilm formation and TDA production. tdaC, a
      key gene for TDA biosynthesis, was expressed only in attached or biofilm-forming
      cells, and expression was induced immediately after initial attachment. In
      conclusion, c-di-GMP signalling controls biofilm formation and biofilm-associated
      traits in R. mobilis and, as suggested by presence of GGDEF and EAL domain
      protein genes, also in other Roseobacter clade species. 

PMID- 24118908
TI  - Clinical characteristics according to depression screening tools in patients with
      Alzheimer's disease: view from self, caregiver-reported and drug-intervention
      pattern.
AB  - AIM: Depression in Alzheimer's disease (AD) has different clinical manifestations
      from primary depression of non-demented patients. We designed the present study
      to explore the following: (i) to determine the clinical characteristics of
      patients with and without depression according to observational and subjective
      depression screening scale; and (ii) to examine the depression prevalence rate in
      patients with AD according to these criteria. METHODS: The Geriatric Depression
      Scale (GDS, observational scale) and Neuropsychiatry Inventory Depression
      subscale (NPI-D; subjective scale) were administered to 257 patients with drug
      naive probable AD. The study groups were classified into the three subgroups of
      "no-depression", GDS depression and NPI-DS (NPI-D significant) depression group,
      and the clinical characteristics of these subgroups were examined. RESULTS: The
      NPI-DS depression group showed lower scores on the Korean version of the Mini
      Mental State Examination compared with the no-depression group, and higher NPI
      subdomain scores compared with other groups. The GDS depression group showed
      higher NPI motor subdomain scores compared with the no-depression group.
      Depression defined by NPI-DS was the least frequent (10.5%), and NPI-DA (NPI-D
      any) was the most frequent (56.4%). The prevalence of depression defined by GDS
      and anti-depressant usage was 30.0% and 16.0% each. The level of agreement
      between the screening tools determined through the kappa index was from low to
      moderate. CONCLUSIONS: The present study showed that different depression
      screening tools revealed a different prevalence and poor concordance rate among
      depression screening tools. Considering lower cognitive functions and higher BPSD
      symptoms in the NPI-DS depression group, NPI-DS could be associated with disease
      severity in AD patients. However, the clinical significance of GDS remains
      uncertain.

PMID- 24118909
TI  - Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal
      insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus.
AB  - AIMS: To assess the pharmacokinetics (PK) and glucodynamics (GD) of LY2605541 in
      patients with type 2 diabetes mellitus. METHODS: This parallel-group, open-label,
      dose-escalation study examined the PK and GD of basal insulin LY2605541 after
      single and multiple-dose administration. Fixed doses of LY2605541 (0.33-1.00
      U/kg) were given once-daily (QD) for 14 days to insulin-treated patients with
      type 2 diabetes. A 24-h euglycaemic glucose clamp was conducted on days 1 and 14.
      RESULTS: PK steady state was achieved within 7-10 days and the peak-to-trough
      fluctuation was <2, translating to a nearly 'peakless' glucose infusion rate at
      steady state and with a duration of action of at least 24 h. Across dose levels
      t1/2 ranged from 44.7 to 75.5 h (~2-3 days). As steady state was achieved, there
      were dose-dependent reductions in the prandial insulin dose and in fasting blood
      glucose, which decreased to 60-100 mg/dl across dose levels. Within-patient
      variability was <14 and <26% for the area under the concentration versus time
      curve (AUC) of the 8-point blood glucose profile and fasting blood glucose,
      respectively. The nocturnal glucose control between 03:00 and 09:00 hours was
      relatively unchanged. Mild hypoglycaemia was the most common adverse event.
      CONCLUSIONS: In this Phase I study of fixed LY2605541 doses without titration,
      LY2605541 was well-tolerated and demonstrated a flat PK and GD profile
      accompanied by glucose normalization, prandial insulin dose reduction and no
      severe hypoglycaemia.

PMID- 24118910
TI  - New ideas for future studies of Helicobacter pylori.
AB  - Gastric cancer (GC) is one of the inflammation-associated cancers. Helicobacter
      pylori is now thought to be responsible for more than 95% of all GCs, and its
      development is associated with at least four mechanisms that lead to genetic
      instability of the gastric mucosa. The risk of developing GC can be predicted by
      assessing the extent and severity of corpus atrophy and the degree of risk can be
      estimated by using non-invasive methods such as the pepsinogen test, or
      endoscopic or histological cancer risk scoring systems such as the operative link
      for gastritis assessment. The eradication of H. pylori will stop the progression
      of gastritis, prevent atrophy and thus decrease the risk of cancer. H. pylori
      eradication should follow the dictum "use what works best locally". There are
      several new developments in the diagnosis and treatment of H. pylori infection
      including serological antibody, fluorescent in situ hybridization and antibiotic
      resistance tests. It is still necessary to develop a preventive or therapeutic
      vaccine to prevent GC. 

PMID- 24118911
TI  - PEX5, the shuttling import receptor for peroxisomal matrix proteins, is a redox
      sensitive protein.
AB  - Peroxisome maintenance depends on the import of nuclear-encoded proteins from the
      cytosol. The vast majority of these proteins is destined for the peroxisomal
      lumen and contains a C-terminal peroxisomal targeting signal, called PTS1. This
      targeting signal is recognized in the cytosol by the receptor PEX5. After docking
      at the peroxisomal membrane and release of the cargo into the organelle matrix,
      PEX5 is recycled to the cytosol through a process requiring monoubiquitination of
      an N-terminal, cytosolically exposed cysteine residue (Cys11 in the human
      protein). At present, the reason why a cysteine, and not a lysine residue, is the
      target of ubiquitination remains unclear. Here, we provide evidence that PTS1
      protein import into human fibroblasts is a redox-sensitive process. We also
      demonstrate that Cys11 in human PEX5 functions as a redox switch that regulates
      PEX5 activity in response to intracellular oxidative stress. Finally, we show
      that exposure of human PEX5 to oxidized glutathione results in a ubiquitination
      deficient PEX5 molecule, and that substitution of Cys11 by a lysine can
      counteract this effect. In summary, these findings reveal that the activity of
      PEX5, and hence PTS1 import, is controlled by the redox state of the cytosol. The
      potential physiological implications of these findings are discussed. 

PMID- 24118912
TI  - Novel inhibitory function of miR-125b in melanogenesis.
AB  - MicroRNAs are known to be the important regulators of skin physiology and
      considered as new therapeutic targets to treat skin diseases. In this study, miR
      125b was identified as a potent regulator of steady-state melanogenesis. We found
      that the expression of miR-125b was inversely related to pigment levels. A miR
      125b mimic decreased the expression of pigmentation-related gene and melanin
      content, implying that miR-125b functions to decrease pigmentation. Moreover, we
      observed that the reduction in miR-125b expression in pigmented cells was at
      least partially due to the hypermethylation of the MIR125B-1 promoter, and miR
      125b expression was regulated by intracellular cAMP levels. 

PMID- 24118913
TI  - Effects of glycolic acid chemical peeling on facial pigment deposition:
      evaluation using novel computer analysis of digital-camera-captured images.
AB  - BACKGROUND: Chemical peeling is becoming increasingly popular for skin
      rejuvenation in dermatological cosmetic medicine. However, the improvements seen
      with chemical peeling are often very minor, and it is difficult to conduct a
      quantitative assessment of pre- and post-treatment appearance. AIMS: We report
      the pre- and postpeeling effects for facial pigment deposition using a novel
      computer analysis method for digital-camera-captured images. PATIENTS/METHODS:
      Glycolic acid chemical peeling was performed a total of 5 times at 2-week
      intervals in 23 healthy women. We conducted a computer image analysis by
      utilizing Robo Skin Analyzer CS 50 and Clinical Suite 2.1 and then reviewed each
      parameter for the area of facial pigment deposition pre- and post-treatment.
      Parameters were pigmentation size and four pigmentation categories: little
      pigmentation and three levels of marked pigmentation (Lv1, 2, and 3) based on
      detection threshold. Each parameter was measured, and the total area of facial
      pigmentation was calculated. RESULTS: The total area of little pigmentation and
      marked pigmentation (Lv1) was significantly reduced. On the other hand, a
      significant difference was not observed for the total area of marked pigmentation
      Lv2 and Lv3. CONCLUSION: This suggests that glycolic acid chemical peeling has an
      effect on small facial pigment disposition or has an effect on light pigment
      deposition. As the Robo Skin Analyzer is useful for objectively quantifying and
      analyzing minor changes in facial skin, it is considered to be an effective tool
      for accumulating treatment evidence in the cosmetic and esthetic skin field.

PMID- 24118914
TI  - Immediate Occlusal versus Non-Occlusal Loading of Implants: A Randomized Clinical
      Pilot Study.
AB  - BACKGROUND: Immediate occlusal and non-occlusal loading protocols have been
      discussed and, despite varying success rates, are considered viable in selected
      cases. Preoperative implant planning and intraoperative transfer are essential to
      the success of implant-supported reconstructions in partially or completely
      edentulous jaws. PURPOSE: This study was performed to compare clinical outcomes
      of immediate occlusal versus non-occlusal loading of posterior implants.
      MATERIALS AND METHODS: Of 19 patients with 52 screw-type implants replacing
      mandibular molars or premolars, nine patients with 21 implants were randomized to
      a study group that received immediate restorations with occlusal loading, whereas
      10 patients with 31 implants were randomized to a control group that received
      provisional restorations without occlusal loading. Occlusal loading was defined
      as full loading in maximum intercuspidation. Single-tooth or splinted multiunit
      restorations were incorporated by screw retention or cementation. Marginal bone
      defects (MBD), implant survival, and implant success were evaluated 12 months
      after insertion. RESULTS: Both groups revealed similar MBD levels consistent with
      previous reports. No implants were lost (overall survival: 100%) or found to fail
      (overall success: 100%). No significant intergroup differences were noted for any
      of the evaluated parameters. CONCLUSIONS: Immediate restorations in partially
      edentulous mandibles demonstrated successful clinical and radiographic 12-month
      results. Larger long-term prospective studies are needed to confirm the final
      evidence and predictability of immediate functional loading as a standard
      treatment concept for partially edentulous jaws.

PMID- 24118915
TI  - The interaction of early life experiences with COMT val158met affects anxiety
      sensitivity.
AB  - The pathogenesis of anxiety disorders is considered to be multifactorial with a
      complex interaction of genetic factors and individual environmental factors.
      Therefore, the aim of this study was to examine gene-by-environment interactions
      of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase
      A (MAOA) with life events on measures related to anxiety. A sample of healthy
      subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was
      genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem
      repeats), and was assessed for childhood adversities [Childhood Trauma
      Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and
      anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and
      interaction effects of genotype, environment and gender on measures related to
      anxiety were assessed by means of regression analyses. Association analysis
      showed no main gene effect on either questionnaire score. A significant
      interactive effect of childhood adversities and COMT genotype was observed:
      Homozygosity for the low-active met allele and high CTQ scores was associated
      with a significant increment of explained ASI variance [R(2) = 0.040, false
      discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with
      respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low
      active MAOA allele who reported more aversive experiences in childhood exhibited
      a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10).
      Early aversive life experiences therefore might increase the vulnerability to
      anxiety disorders in the presence of homozygosity for the COMT 158met allele or
      low-active MAOA-uVNTR alleles.

PMID- 24118917
TI  - Involuntary admissions under the Mental Health Act 2007 (New South Wales): a
      comparison of patients detained by ambulance officers, medical practitioners and
      accredited persons in an emergency department.
AB  - OBJECTIVE: The Mental Health Act (MHA) 2007 (New South Wales [NSW]) is used to
      transport to, detain and treat individuals in a mental health facility. Patients
      are frequently taken to EDs under the MHA or detained in the ED for a mental
      health assessment. In NSW, medical practitioners, accredited persons, police and
      more recently ambulance officers, are authorised to write certificates under the
      MHA. There is an absence of research on the use of the MHA in NSW EDs. The
      primary research question for this study was: 'What is the involuntary admission
      rate for persons detained under the MHA in an NSW tertiary referral ED?' METHODS:
      After gaining ethics approval, the research team prospectively collected the MHA
      certificates written for patients in the ED over a 3 month period from February
      to May 2011. The research team reviewed the MHA certificate and medical records
      to characterise demographics, outcome, length of stay in ED and certificate
      suitability. Outcomes of interest were involuntary psychiatric admission or any
      inpatient admission, and were compared between the different professional groups
      completing the certificate. RESULTS: The involuntary admission rate for patients
      certified by ambulance officers under the NSW MHA was 27%, compared with a 60%
      involuntary admission rate when certified by medical practitioners or accredited
      persons. The mean average length of stay in the ED for patients certified under
      the MHA was 10 h. Seventy-five per cent of patients presented out of hours.
      CONCLUSION: Ambulance officer certification was a poor predictor of involuntary
      psychiatric admission in the Royal Prince Alfred Hospital Emergency Department.
      ED physicians should have the authority to revoke the certificate if, following
      assessment and treatment, the patient no longer fulfils criteria for detention
      under the MHA.

PMID- 24118916
TI  - A comparison of estimated glomerular filtration rates using Cockcroft-Gault and
      the Chronic Kidney Disease Epidemiology Collaboration estimating equations in HIV
      infection.
AB  - OBJECTIVES: The aim of this study was to determine whether the Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft-Gault (CG)-based
      estimated glomerular filtration rates (eGFRs) performs better in the cohort
      setting for predicting moderate/advanced chronic kidney disease (CKD) or end
      stage renal disease (ESRD). METHODS: A total of 9521 persons in the EuroSIDA
      study contributed 133 873 eGFRs. Poisson regression was used to model the
      incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73
      m(2) , respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs.
      RESULTS: Of 133 873 eGFR values, the ratio of CG to CKD-EPI was >= 1.1 in 22 092
      (16.5%) and the difference between them (CG minus CKD-EPI) was >= 10 mL/min/1.73
      m(2) in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when
      CG was not standardized for body surface area (BSA). A total of 403 persons
      developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up
      (PYFU); 95% confidence interval (CI) 8.0-9.8] and 364 using CKD-EPI (incidence
      7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived
      eGFRs at predicting ESRD (n = 36) and death (n = 565), as measured by the Akaike
      information criterion. CG-based moderate and advanced CKDs were associated with
      ESRD [adjusted incidence rate ratio (aIRR) 7.17; 95% CI 2.65-19.36 and aIRR
      23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and
      advanced CKDs (aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03,
      respectively). CONCLUSIONS: Differences between eGFRs using CG adjusted for BSA
      or CKD-EPI were modest. In the absence of a gold standard, the two formulae
      predicted clinical outcomes with equal precision and can be used to estimate GFR
      in HIV-positive persons.

PMID- 24118918
TI  - In vitro assessment of 36 CYP2C9 allelic isoforms found in the Chinese population
      on the metabolism of glimepiride.
AB  - Of the 57 reported CYP2C9 alleles, to date, 36 of them have been identified in
      the Chinese population. The aim of this study was to assess the catalytic
      characteristics of these allelic isoforms and their effects on the metabolism of
      glimepiride in vitro. Baculovirus-mediated expressing system was used to highly
      express wild-type and the 35 CYP2C9 allelic variants in insect cell microsomes.
      Then, the enzymatic characteristics of each variant were evaluated using
      glimepiride as the substrate. Reactions were performed at 37 degrees C with the
      insect microsomes and 0.125-10 MUM glimepiride for 40 min. After termination, the
      products were extracted and used for signal collection by LC-MS/MS. Of the 36
      tested CYP2C9 allelic isoforms, only four variants (CYP2C9.40, CYP2C9.47,
      CYP2C9.51 and CYP2C9.54) exhibited similar relative clearance values to that of
      wild-type CYP2C9.1. In addition, one variant (CYP2C9.36) showed a higher
      intrinsic clearance value than the wild-type protein, while the remaining 30
      CYP2C9 allelic isoforms exhibited significantly decreased clearance values (from
      0.1% to 87.2%) compared to CYP2C9.1. This study provided the most comprehensive
      data on the enzymatic activities of all reported CYP2C9 variants in the Chinese
      population with regard to the commonly used antidiabetic drug, glimepiride. Our
      results indicate that most of the tested rare alleles significantly decrease the
      catalytic activity of CYP2C9 variants towards glimepiride hydroxylation in vitro.

PMID- 24118919
TI  - Comparative toxicogenomic responses of mercuric and methyl-mercury.
AB  - BACKGROUND: Mercury is a ubiquitous environmental toxicant that exists in
      multiple chemical forms. A paucity of information exists regarding the
      differences or similarities by which different mercurials act at the molecular
      level. RESULTS: Transcriptomes of mixed-stage C. elegans following equitoxic sub
      , low- and high-toxicity exposures to inorganic mercuric chloride (HgCl2) and
      organic methylmercury chloride (MeHgCl) were analyzed. In C. elegans, the
      mercurials had highly different effects on transcription, with MeHgCl affecting
      the expression of significantly more genes than HgCl2. Bioinformatics analysis
      indicated that inorganic and organic mercurials affected different biological
      processes. RNAi identified 18 genes that were important in C. elegans response to
      mercurial exposure, although only two of these genes responded to both
      mercurials. To determine if the responses observed in C. elegans were
      evolutionarily conserved, the two mercurials were investigated in human
      neuroblastoma (SK-N-SH), hepatocellular carcinoma (HepG2) and embryonic kidney
      (HEK293) cells. The human homologs of the affected C. elegans genes were then
      used to test the effects on gene expression and cell viability after using siRNA
      during HgCl2 and MeHgCl exposure. As was observed with C. elegans, exposure to
      the HgCl2 and MeHgCl had different effects on gene expression, and different
      genes were important in the cellular response to the two mercurials. CONCLUSIONS:
      These results suggest that, contrary to previous reports, inorganic and organic
      mercurials have different mechanisms of toxicity. The two mercurials induced
      disparate effects on gene expression, and different genes were important in
      protecting the organism from mercurial toxicity.

PMID- 24118920
TI  - Child overweight in general practice - parents' beliefs and expectations - a
      questionnaire survey study.
AB  - BACKGROUND: Care for overweight children in general practice involves
      collaboration with parents. Acknowledging the parents' frames of references is a
      prerequisite for successful management. We therefore aimed to analyse parental
      beliefs about the presumed causes and consequences of overweight in children and
      expectations towards the GP. Moreover, we aimed at comparing the beliefs and
      expectations of parents of non-overweight children (NOWC) and parents of
      overweight children (OWC). METHODS: A cross-sectional survey. Data were obtained
      from a questionnaire exploring parents' beliefs and expectations regarding
      overweight in children. The questionnaires were completed by parents following
      their child's participation in the five-year preventive child health examination
      (PCHE).Parental agreement upon statements concerning beliefs and expectations
      regarding overweight in children was measured on a Likert scale. Differences in
      levels of agreement between parents of non-overweight children and parents of
      overweight children were analysed using Chi-squared test and Fisher's exact test.
      RESULTS: Parents of 879 children completed and returned questionnaires. Around
      three fourths of the parents agreed that overweight was a health problem. A
      majority of parents (93%) agreed that the GP should call attention to overweight
      in children and offer counselling on diet and exercise. Almost half of the
      parents expected a follow-up programme. Parents of overweight children seemed to
      agree less upon some of the proposed causes of overweight, e.g. inappropriate
      diet and lack of exercise. These parents also had stronger beliefs about
      overweight disappearing by itself as the child grows up. CONCLUSIONS: According
      to parental beliefs and expectations, general practice should have an important
      role to play in the management of child overweight. Moreover, our findings
      suggest that GPs should be aware of the particular beliefs that parents of
      overweight children may have regarding causes of overweight in their child.

PMID- 24118921
TI  - Hepatic molecular effects of rosiglitazone in human non-alcoholic steatohepatitis
      suggest long-term pro-inflammatory damage.
AB  - AIM: Glitazones are agonists of peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) and have been proposed for the treatment of non-alcoholic
      steatohepatitis (NASH). However, efficacy results are conflicting and hepatic
      molecular changes induced by glitazones are mostly unknown. The aim of this study
      was to analyze the hepatic inflammatory and fibrogenic molecular effects of
      rosiglitazone in NASH patients. METHODS: Hepatic expression of PPAR-gamma and
      several inflammatory/immune and fibrogenic genes were studied before and after a
      12-month treatment with rosiglitazone or placebo in 25 patients with NASH from
      the Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) trial. RESULTS:
      Treatment with rosiglitazone induced hepatic PPAR-gamma expression but increased
      the expression of several pro-inflammatory genes such as SOCS3 and TLR4. There
      was a significant reduction in mRNA and protein levels of alpha-smooth muscle
      actin, compatible with previously documented antifibrotic actions of
      rosiglitazone on stellate cells. However, there was no change in type 1 collagen
      and transforming growth factor-beta expression thus suggesting an offset of the
      antifibrogenic actions by long-term pro-inflammatory changes. CONCLUSION: In NASH
      patients, hepatic PPAR-gamma induction by rosiglitazone was associated with
      increased hepatic expression of pro-inflammatory genes which may explain the lack
      of long-term histological benefit shown in human studies with this drug. It is
      unclear whether these results are a class effect of PPAR-gamma agonists or a
      specific effect of rosiglitazone.

PMID- 24118922
TI  - Targeting p53 in melanoma.

PMID- 24118923
TI  - A retrospective study of pediatric traumatic dental injuries in Xi'an, China.
AB  - BACKGROUND/AIM: Pediatric traumatic dental injury is an important public health
      problem because of its high prevalence, severe physical or psychological impacts,
      and high prevention and treatment costs. This study aimed to determine the
      distributive features of pediatric traumatic dental injury in a university dental
      hospital in Xi'an, China. MATERIALS AND METHODS: Children (aged 1 to 15 years)
      visiting the hospital from February 2011 to May 2012 as a result of dental trauma
      were investigated. Trauma-related information was recorded and analyzed. RESULTS:
      Most of the traumas occurred in children aged 7 to 12 years and affected the
      maxillary incisors. Of all the children involved, 17.2% had overjet. Concussion,
      enamel-dentin-pulp fracture, avulsion, and lateral luxation occurred more in the
      primary dentition (20.9%, 16.5%, 14.3%, and 13.2%, respectively). However, most
      traumas to the permanent dentition were enamel-dentin-pulp fractures and enamel
      dentin fractures (33.7% and 29.1%, respectively). Most traumas were luxations (n
      = 156) in the 1- to 6-year-old group, while fractures were more common in the 7-
      to 12- and >13-year-old groups (n = 549, 84; P < 0.001). In total, 357 urban
      children had access to immediate medical care, whereas only 12 rural children
      were able to access a clinic within 24 h after injury (P < 0.001). CONCLUSION:
      Based on the information presented in this survey, the government should focus on
      medical development in rural settings and should attempt to balance the
      distribution of medical resources between urban and rural areas. Educational and
      preventive programs should also be promoted to enhance the guardians' awareness
      regarding pediatric traumatic dental injuries.

PMID- 24118924
TI  - Survival and beneficial properties of lactic acid bacteria from raniculture
      subjected to freeze-drying and storage.
AB  - AIM: To evaluate the effect of freeze-drying and storage conditions on the
      viability and beneficial properties of lactic acid bacteria (LAB) for
      raniculture. METHODS AND RESULTS: Lactococcus lactis CRL 1584, L. lactis CRL
      1827, Lactococcus garvieae CRL 1828 and Lactobacillus plantarum CRL 1606
      viability under different conditions was studied. 10% lactose and 5% skim milk +
      5% lactose were excellent lyoprotectants, but 5% skim milk + 5% lactose and whey
      protein concentrated (WPC) or WPC + sugars were the lower cost lyoprotective
      options. The effect of temperature depended on both lyoprotectants and storage
      time. Thus, for Lactococcus, skim milk, skim milk + sucrose and WPC + sucrose
      were selected for lyophilization and storage at 4 degrees C and skim milk +
      lactose for 25 degrees C. For Lact. plantarum CRL 1606, the best lyoprotectants
      for lyophilization and storage at 4 degrees C were milk + sugars and WPS +
      sucrose and, at 25 degrees C, skim milk + sucrose. CONCLUSIONS: Lactic acid
      bacteria viability after freeze-drying was strain-specific and depended on the
      lyoprotectant used. Highest viability was obtained when stored at 4 degrees C,
      and the beneficial properties remained stable for 18 months independently of
      storage temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: The studies reported
      for the first time in this work are of primary interest to obtain dried bacteria
      to be included in beneficial products for raniculture.

PMID- 24118925
TI  - Fracture Resistance and Mode of Failure of Ceramic versus Titanium Implant
      Abutments and Single Implant-Supported Restorations.
AB  - BACKGROUND: The material of choice for implant-supported restorations is affected
      by esthetic requirements and type of abutment. PURPOSE: This study compares the
      fracture resistance of different types of implant abutments and implant-supported
      restorations and their mode of failure. MATERIALS AND METHODS: Forty-five
      Oraltronics Pitt-Easy implants (Oraltronics Dental Implant Technology GmbH,
      Bremen, Germany) (4 mm diameter, 10 mm length) were embedded in clear
      autopolymerizing acrylic resin. The implants were randomly divided into three
      groups, A, B and C, of 15 implants each. In group A, titanium abutments and metal
      ceramic crowns were used. In group B, zirconia ceramic abutments and In-Ceram
      Alumina crowns were used. In group C, zirconia ceramic abutments and IPS Empress
      Esthetic crowns were used. Specimens were tested to failure by applying load at
      130 degrees  from horizontal plane using an Instron Universal Testing Machine.
      Subsequently, the mode of failure of each specimen was identified. RESULTS:
      Fracture resistance was significantly different between groups (p < .05). The
      highest fracture loads were associated with metal-ceramic crowns supported by
      titanium abutments (p = .000). IPS Empress crowns supported by zirconia abutments
      had the lowest fracture loads (p = .000). Fracture modes of metal-ceramic crowns
      supported by titanium abutments included screw fracture and screw bending.
      Fracture of both crown and abutment was the dominant mode of failure of In
      Ceram/IPS Empress crowns supported by zirconia abutments. CONCLUSIONS: Metal
      ceramic crowns supported by titanium abutments were more resistant to fracture
      than In-Ceram crowns supported by zirconia abutments, which in turn were more
      resistant to fracture than IPS Empress crowns supported by zirconia abutments. In
      addition, failure modes of restorations supported by zirconia abutments were more
      catastrophic than those for restorations supported by titanium abutments.

PMID- 24118926
TI  - Assessment of normal erythropoiesis by flow cytometry: important considerations
      for specimen preparation.
AB  - INTRODUCTION: The extension of quantitative flow cytometric studies to the
      erythroid lineage in patients with suspected myelodysplastic syndrome has
      prompted a reassessment of cell surface antigen expression during normal
      erythropoiesis. Erythropoiesis in normal and pathologic bone marrows was studied
      to determine the expected antigenic relationships of maturing erythroid cells.
      METHODS: A total of 200 bone marrow specimens were evaluated by multidimensional
      flow cytometry (MDF). Samples were prepared using either NH4 Cl lysis or Ficoll
      density gradient separation. RESULTS: Normal erythroid development is described
      as a two-step process observable with the intensity relationships between CD235a,
      CD71, CD45, CD105, CD34, CD117, and CD36. The variability of these intensities
      (CV) was determined. A comparison of processing techniques determined lysis is
      the optimal analytic technique for the analysis of early-stage erythroid cells.
      Nucleic acid staining with DRAQ5 revealed that Ficoll allows for the analysis of
      reticulocytes and mature erythrocytes otherwise eliminated by lysis. CONCLUSION:
      These data demonstrate while lysis alters the light scatter characteristics of
      erythroid precursors, it did not alter quantitative antigen expression or nucleic
      acid content. The expected variability in antigen intensities is defined. These
      studies provide a basis for a comparison of erythroid development between normal
      individuals and those with erythroid dysplasia associated with myelodysplastic
      syndromes.

PMID- 24118927
TI  - Response of the methanogenic microbial communities in Amazonian oxbow lake
      sediments to desiccation stress.
AB  - Methanogenic microbial communities in soil and sediment function only when the
      environment is inundated and anoxic. In contrast to submerged soils, desiccation
      of lake sediments happens only rarely. However, some predictions suggest that
      extreme events of drying will become more common in the Amazon region, and this
      will promote an increase in sediments drying and exposure. We asked whether and
      how such methanogenic communities can withstand desiccation stress. Therefore, we
      determined the rates and pathways of CH(4) production (analysis of CH(4) and
      delta(13) C of CH(4), CO(2) and acetate), the copy numbers of bacterial and
      archaeal 16S rRNA genes and mcrA genes (quantitative PCR), and the community
      composition of Archaea and Bacteria (T-RFLP and pyrosequencing) in oxbow lake
      sediments of rivers in the Brazilian Amazon region. The rivers were of white
      water, black water and clear water type. The measurements were done with sediment
      in fresh state and after drying and rewetting. After desiccation and rewetting
      the composition of both, the archaeal and bacterial community changed. Since lake
      sediments from white water rivers exhibited only negligible methanogenic
      activity, probably because of relatively high iron and low organic matter
      content, they were not further analysed. The other sediments produced CH(4), with
      hydrogenotrophic methanogenesis usually accounting for > 50% of total activity.
      After desiccation and rewetting, archaeal and bacterial gene copy numbers
      decreased. The bacterial community showed a remarkable increase of Clostridiales
      from about 10% to > 30% of all Bacteria, partially caused by proliferation of
      specific taxa as the numbers of OTU shared with fresh sediment decreased from
      about 9% to 3%. Among the Archaea, desiccation specifically enhanced the relative
      abundance of either Methanocellales (black water) and/or Methanosarcinaceae
      (clear water). Despite the changes in gene copy numbers and composition of the
      microbial community, rates of CH(4) production even increased after desiccation
      rewetting, demonstrating that the function of the methanogenic microbial
      community had not been impaired. This result indicates that the increase in
      extreme events of drying may increase methane production in flooded sediments.

PMID- 24118929
TI  - DCE-MRI findings of invasive aspergillosis in patient with acute myeloid
      leukemia.
AB  - Thoracic radiography and high resolution computerized tomography is used to
      diagnose pulmonary infections in immunosuppressed patients, although in some
      cases these do not provide enough information about the lesion. Dynamic contrast
      enhanced magnetic resonance imaging may be useful in these cases, especially for
      the characterization of cavitary lesions and assessment of their contrast
      diffusion. 

PMID- 24118928
TI  - Gender differences in coerced patients with schizophrenia.
AB  - BACKGROUND: Despite the recent increase of research interest in involuntary
      treatment and the use of coercive measures, gender differences among coerced
      schizophrenia patients still remain understudied. It is well recognized that
      there are gender differences both in biological correlates and clinical
      presentations in schizophrenia, which is one of the most common diagnoses among
      patients who are treated against their will. The extent to which these
      differences may result in a difference in the use of coercive measures for men
      and women during the acute phase of the disease has not been studied. METHODS:
      291 male and 231 female coerced patients with schizophrenia were included in this
      study, which utilized data gathered by the EUNOMIA project (European Evaluation
      of Coercion in Psychiatry and Harmonization of Best Clinical Practice) and was
      carried out as a multi-centre prospective cohort study at 13 centers in 12
      European countries. Sociodemographic and clinical characteristics, social
      functioning and aggressive behavior in patients who received any form of coercive
      measure (seclusion and/or forced medication and/or physical restraint) during
      their hospital stay were assessed. RESULTS: When compared to the non-coerced
      inpatient population, there was no difference in sociodemographic or clinical
      characteristics across either gender. However coerced female patients did show a
      worse social functioning than their coerced male counterparts, a finding which
      contrasts with the non-coerced inpatient population. Moreover, patterns of
      aggressive behavior were different between men and women, such that women
      exhibited aggressive behavior more frequently, but men committed severe
      aggressive acts more frequently. Staff used forced medication in women more
      frequently and physical restraint and seclusion more frequently with men.
      CONCLUSIONS: Results of this study point towards a higher threshold of aggressive
      behavior the treatment of women with coercive measures. This may be because less
      serious aggressive actions trigger the application of coercive measures in men.
      Moreover coerced women showed diminished social functioning, and more importantly
      more severe symptoms from the "excitement/hostile" cluster in contrast to coerced
      men. National and international recommendation on coercive treatment practices
      should include appropriate consideration of the evidence of gender differences in
      clinical presentation and aggressive behaviors found in inpatient populations.

PMID- 24118930
TI  - Songbirds as general transmitters but selective amplifiers of Borrelia
      burgdorferi sensu lato genotypes in Ixodes rinicus ticks.
AB  - We investigated to what extent a European songbird (Parus major) selectively
      transmits and amplifies Borrelia burgdorferi s.l. bacteria. Borrelia-naive birds
      were recurrently exposed to Ixodes ricinus nymphs carrying a community of more
      than 34 5S-23S genotypes belonging to five genospecies (Borrelia garinii,
      Borrelia valaisiana, Borrelia afzelii, B. burgdorferi s.s. and Borrelia
      spielmanii). Fed ticks were screened for Borrelia after moulting. We found
      evidence for co-feeding transmission of avian and possibly also mammalian
      genotypes. Throughout the course of infestations, the infection rate of B.
      garinii and B. valaisiana increased, indicating successful amplification and
      transmission, while the infection rate for B. afzelii, B. burgdorferi s.s and B.
      spielmanii tended to decrease. Within the B. garinii and B. valaisiana genotype
      communities, certain genotypes were transmitted more than others. Moreover, birds
      were able to host mixed infections of B. garinii and B. valaisiana, as well as
      mixed infections of genotypes of the same genospecies. We experimentally show
      that resident songbirds transmit a broad range of Borrelia genotypes, but
      selectively amplify certain genotypes, and that one bird can transmit
      simultaneously several genotypes. Our results highlight the need to explicitly
      consider the association between genotypes and hosts, which may offer
      opportunities to point out which hosts are most responsible for the Borrelia
      presence in questing ticks. 

PMID- 24118931
TI  - Randomized, 1-year comparison of three ways to initiate and advance insulin for
      type 2 diabetes: twice-daily premixed insulin versus basal insulin with either
      basal-plus one prandial insulin or basal-bolus up to three prandial injections.
AB  - AIM: Many patients with type 2 diabetes mellitus (T2DM) initiate insulin therapy
      when other treatments fail; how best to do this is poorly defined. METHODS:
      People with T2DM [n = 588; glycated haemoglobin A1C (A1C) >7.0%, mean baseline
      9.4%] were randomized to twice-daily premixed protamine-aspart/aspart insulin (PM
      - 2), once-daily insulin glargine plus zero to one prandial insulin glulisine
      injection (G + 1), or insulin glargine plus zero to three prandial injections (G
      + 3). Insulin was titrated for 60 weeks. Efficacy and safety outcomes were
      assessed. RESULTS: Discontinuation rates were 53 of the 194 (27%), 44 of the 194
      (23%) and 38 of the 194 (20%), for PM - 2, G + 1 and G + 3. Glycaemic control
      improved in all groups (A1C 7.2 +/- 1.37, 7.1 +/- 1.68 and 7.0 +/- 1.21% at 60
      weeks; 7.5 +/- 1.29, 7.2 +/- 1.62 and 7.2 +/- 1.63% at endpoint). G + 1 was
      statistically non-inferior to PM - 2 in reducing A1C. G + 3 was slightly superior
      to PM - 2 in attaining <7.0% at 60 weeks, but only when the analysis included
      Good Clinical Practice non-adherent sites. Hypoglycaemia with plasma glucose <2.8
      mmol/l was more frequent with PM - 2 versus G + 1 and G + 3; [adjusted incidence:
      46 (p = 0.0087) vs. 33 (p = 0.0045) and 31.5%; events per patient-year: 1.9 vs.
      0.8 and 0.9, p <= 0.0001]. Insulin dosage and weight-gain were similar.
      CONCLUSION: Basal insulin plus a single prandial injection is as effective in
      improving glycaemic control as premixed insulin. Full basal-prandial therapy is
      only slightly more effective than premixed insulin. Stepwise basal-prandial
      regimens improve glycaemic control with less hypoglycaemia than twice-daily
      premixed insulin.

PMID- 24118932
TI  - Multiple listing for pediatric heart transplantation in the U.S.A.: analysis of
      OPTN registry data from 1995 through 2009.
AB  - Multiple listing is associated with shorter waitlist durations and increased
      likelihood of transplantation for renal candidates. Little is known about
      multiple listing in pediatric heart transplantation. We examined the prevalence
      and outcomes of multiple listing using OPTN data from 1995 through 2009.
      Characteristics and waitlist outcomes of propensity-score-matched single- and
      multiple-listed patients were compared. Multiple listing occurred in 23 of 6290
      listings (0.4%). Median days between listings was 35 (0-1015) and median duration
      of multiple listings was 32 days (3-363). Among multiple-listed patients, there
      were trends toward less ECMO use (0% vs. 11%, p = 0.1) and more frequent
      requirement for a prospective cross-match (17% vs. 8%, p = 0.08). Multiple-listed
      patients more commonly had private insurance (78% vs. 56%; p = 0.03). Urgency
      status at listing was similar between groups (1/1A: 61% vs. 64%, 1B/2: 39 vs.
      36%; p = 0.45) as were weight, age, diagnosis, ventilator/inotrope use, and
      median income (each p >= 0.17). There was a trend toward increased incidence of
      heart transplantation for multiple-listed patients at three, six, and 24 months
      (50%, 65%, 80%) vs. single-listed patients (40%, 54%, 64%; p = 0.11). Multiple
      listing for pediatric heart transplantation in the USA occurs infrequently and is
      more common in patients with private insurance. 

PMID- 24118933
TI  - Spider toxins comprising disulfide-rich and linear amphipathic domains: a new
      class of molecules identified in the lynx spider Oxyopes takobius.
AB  - In addition to the conventional neurotoxins and cytotoxins, venom of the lynx
      spider Oxyopes takobius was found to contain two-domain modular toxins named
      spiderines: OtTx1a, 1b, 2a and 2b. These toxins show both insecticidal activity
      (a median lethal dose against flesh fly larvae of 75 MUg.g(-1)) and potent
      antimicrobial effects (minimal inhibitory concentrations in the range 0.1-10
      MUm). Full sequences of the purified spiderines were established by a combination
      of Edman degradation, mass spectrometry and cDNA cloning. They are relatively
      large molecules (~ 110 residues, 12.0-12.5 kDa) and consist of two distinct
      modules separated by a short linker. The N-terminal part (~ 40 residues) contains
      no cysteine residues, is highly cationic, forms amphipathic alpha-helical
      structures in a membrane-mimicking environment, and shows potent cytolytic
      effects on cells of various origins. The C-terminal part (~ 60 residues) is
      disulfide-rich (five S-S bonds), and contains the inhibitor cystine knot
      (ICK/knottin) signature. The N-terminal part of spiderines is very similar to
      linear cytotoxic peptides found in various organisms, whereas the C-terminal part
      corresponds to the usual spider neurotoxins. We synthesized the modules of OtTx1a
      and compared their activity to that of full-length mature toxin produced
      recombinantly, highlighting the importance of the N-terminal part, which retained
      full-length toxin activity in both insecticidal and antimicrobial assays. The
      unique structure of spiderines completes the range of two-domain spider toxins.

PMID- 24118934
TI  - The use of mouse models to unravel genetic architecture of physical activity: a
      review.
AB  - The discovery of genetic variants that underlie a complex phenotype is
      challenging. One possible approach to facilitate this endeavor is to identify
      quantitative trait loci (QTL) that contribute to the phenotype and consequently
      unravel the candidate genes within these loci. Each proposed candidate locus
      contains multiple genes and, therefore, further analysis is required to choose
      plausible candidate genes. One of such methods is to use comparative genomics in
      order to narrow down the QTL to a region containing only a few genes. We
      illustrate this strategy by applying it to genetic findings regarding physical
      activity (PA) in mice and human. Here, we show that PA is a complex phenotype
      with a strong biological basis and complex genetic architecture. Furthermore, we
      provide considerations for the translatability of this phenotype between species.
      Finally, we review studies which point to candidate genetic regions for PA in
      humans (genetic association and linkage studies) or use mouse models of PA (QTL
      studies) and we identify candidate genetic regions that overlap between species.
      On the basis of a large variety of studies in mice and human, statistical
      analysis reveals that the number of overlapping regions is not higher than
      expected on a chance level. We conclude that the discovery of new candidate genes
      for complex phenotypes, such as PA levels, is hampered by various factors,
      including genetic background differences, phenotype definition and a wide variety
      of methodological differences between studies. 

PMID- 24118935
TI  - Ascorbic acid prevents protein oxidation in livers of senescence marker protein
      30/gluconolactonase knockout mice.
AB  - AIM: Senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO)
      mice are incapable of synthesizing L-ascorbic acid (AA) in vivo. As AA is known
      to be a water-soluble anti-oxidant, we assessed protein oxidation levels in
      livers from SMP30/GNL KO mice maintained in an AA-insufficient condition.
      METHODS: Livers were collected from male SMP30/GNL KO mice at the ages of 3, 6
      and 12 months, and wild-type (WT) mice at the ages of 3, 6, 12 and 24 months. To
      assess protein oxidation, we measured the content of protein carbonyl, which is a
      major protein oxidation marker. AA levels were measured by 2,4
      dinitrophenylhydrazine method using high-performance liquid chromatography.
      RESULTS: Livers of SMP30/GNL KO mice had just ~5% as much AA as those of WT mice
      from 3 to 12 months-of-age. Protein carbonyl levels in livers from SMP30/GNL KO
      mice were a significant 1.8- to 2.3-fold higher than those from age-atched WT
      mice. To establish that the AA-insufficiency caused this difference, we added AA
      to some drinking water, and examined the effect on AA and protein carbonyl levels
      in livers from SMP30/GNL KO and WT mice. Livers from SMP30/GNL KO mice given
      extra AA had a significantly higher content than those from their deprived
      counterparts. Furthermore, protein carbonyl levels in livers from AA-supplemented
      SMP30/GNL KO mice were significantly lower than those from the SMP30/GNL KO mice
      without AA supplementation. However, added AA did not affect the protein carbonyl
      levels in WT mice. CONCLUSIONS: These results strongly suggest that AA plays an
      important role in preventing protein oxidation in vivo, thus enhancing overall
      health.

PMID- 24118936
TI  - Testicular function during adolescence in boys with type 1 diabetes mellitus
      (T1D): absence of hypogonadism and differences in endocrine profile at the
      beginning and end of puberty.
AB  - AIM: Conflicting results regarding testicular function in adults with type 1
      diabetes (T1D) have been reported, but little is known about Leydig and Sertoli
      cell function during puberty in boys treated with multiple daily insulin doses.
      Our aim was to assess testicular function in boys with T1D. METHODS: Pubertal
      boys with T1D (n = 71) and healthy control boys (Control group; n = 104) who were
      10-18 years were studied. Both groups were matched by pubertal stage, age, and
      BMI. Total testosterone (TT), calculated free testosterone (cfT), SHBG, inhibin
      B, AMH, and gonadotropin levels were determined. RESULTS: At the beginning of
      puberty, the T1D group had higher levels of SHBG (p = 0.003) and similar androgen
      levels than the Control group. At the end of puberty, higher TT, and cfT were
      observed in T1D compared to the Control group (p < 0.01 and p < 0.001,
      respectively). Gonadotropins and AMH were similar in both groups. Regression
      analysis showed that T1D was a significant factor, even after adjusting for
      Tanner stage and BMI-SDS, affecting TT, cFT, and SHBG levels. BMI-SDS was a
      significant factor affecting TT and SHBG levels. Higher HbA1c had a negative
      effect on total testosterone and cFT and a positive effect on SHBG levels in T1D
      boys. CONCLUSION: Adolescents with T1D do not exhibit hypogonadism, as shown by
      normal gonadotropin, testosterone, inhibin B, and AMH levels. However, in T1D
      boys, HbA1c and BMI-SDS had a negative association with testosterone levels.
      Elevated testosterone levels are observed during late puberty, which were not
      present earlier.

PMID- 24118937
TI  - Degenerative lumbar spondylolisthesis with testicular pain.

PMID- 24118939
TI  - The status of serum vitamin D in patients with active Behcet's disease compared
      with controls.
AB  - OBJECTIVE: The aim of this study was to characterize the status of vitamin D in
      patients with active and recently diagnosed Behcet's disease (BD) and the
      relationship between vitamin D levels and BD activity. METHODS AND MATERIALS: In
      this cross sectional study 48 patients with BD and 47 age- and sex-matched
      healthy controls were included. BD was diagnosed by the International Criteria
      for BD. Behcet's patients were new cases who were not on any treatment. BD
      activity was measured by the Iranian Behcet's Disease Dynamic Activity Measure
      (IBDDAM) and Behcet's Disease Current Activity Form (BDCAF). 25(OH)D measured by
      enzyme-linked immunosorbent assay method as an indicator of vitamin D status.
      RESULTS: The mean 25-hydroxyvitamin D (25(OH)D level in the BD group was lower
      than the control group. Insufficiency and deficiency of 25(OH)D in the BD group
      was more common than the control group. No correlation was observed between the
      total IBDDAM, ophthalmic IBDDAM, and BDCAF with 25(OH)D levels. No correlation
      was found between the major symptoms of BD and 25(OH)D value. CONCLUSIONS: Our
      study suggests that deficiency of 25(OH)D may be a trigger factor for BD.

PMID- 24118938
TI  - Protein disulfide isomerase in thrombosis and vascular inflammation.
AB  - Protein disulfide isomerase (PDI) catalyzes disulfide bond oxidation, reduction
      and isomerization during protein synthesis in the endoplasmic reticulum (ER). In
      addition to its critical role in the ER, in vitro and in vivo studies with
      blocking antibodies and conditional knockout mice have demonstrated that cell
      surface PDI is required for thrombosis, hemostasis and vascular inflammation in a
      manner dependent on its isomerase activity. This review will focus on our current
      understanding of the pathophysiologic role of PDI in regulating integrin-mediated
      platelet and neutrophil functions during vascular disease. 

PMID- 24118940
TI  - Beliefs about penis size: validation of a scale for men ashamed about their penis
      size.
AB  - INTRODUCTION: No measures are available for understanding beliefs in men who
      experience shame about the perceived size of their penis. Such a measure might be
      helpful for treatment planning, and measuring outcome after any psychological or
      physical intervention. AIM: Our aim was to validate a newly developed measure
      called the Beliefs about Penis Size Scale (BAPS). METHOD: One hundred seventy
      three male participants completed a new questionnaire consisting of 18 items to
      be validated and developed into the BAPS, as well as various other standardized
      measures. A urologist also measured actual penis size. MAIN OUTCOME MEASURES: The
      BAPS was validated against six psychosexual self-report questionnaires as well as
      penile size measurements. RESULTS: Exploratory factor analysis reduced the number
      of items in the BAPS from 18 to 10, which was best explained by one factor. The
      10-item BAPS had good internal consistency and correlated significantly with
      measures of depression, anxiety, body image quality of life, social anxiety,
      erectile function, overall satisfaction, and the importance attached to penis
      size. The BAPS was not found to correlate with actual penis size. It was able to
      discriminate between those who had concerns or were dissatisfied about their
      penis size and those who were not. CONCLUSIONS: This is the first study to
      develop a scale for measurement of beliefs about penis size. It may be used as
      part of an assessment for men who experience shame about the perceived size of
      their penis and as an outcome measure after treatment. The BAPS measures various
      manifestations of masculinity and shame about their perceived penis size
      including internal self-evaluative beliefs; negative evaluation by others;
      anticipated consequences of a perceived small penis, and extreme self
      consciousness.

PMID- 24118941
TI  - The consultants' role in the referring process with general practitioners:
      partners or adjudicators? a qualitative study.
AB  - BACKGROUND: Within the health system, communication between the different levels
      of care is essential for the patients' clinical pathways and medical treatment.
      This includes the referral process: how and why patients are sent from the
      primary care level to specialist health services. We wanted to identify and
      describe hospital consultants' reflections on and attitudes to the referral
      process and cooperation with general practitioners (GPs). METHODS: A qualitative
      study of semi-structured interviews with 13 hospital consultants representing
      eight different specialties, analyzed using systematic text condensation.
      Interviews conducted from February 2011 to October 2012. RESULTS: The consultants
      reported a considerable workload assessing referrals from GPs and prioritizing
      patients for specialist services. National guidelines were used as well as
      individual standards and guidelines. Good referrals could make the prioritization
      process easier. The specialists expressed a deep concern about securing a fair
      priority of patients and a willingness to give reasonable advice back to the
      referring GP when rejecting a referral. Better communication, such as a telephone
      call to confer with a hospital specialist before referral, was wanted.
      CONCLUSIONS: Better communication and cooperation between hospital consultants
      and GPs could make the referral process more balanced, and the participants more
      like partners.

PMID- 24118943
TI  - Isolation and characterization of baker's yeast capable of strongly activating a
      macrophage.
AB  - A physiological function of the beta-glucans which constitute the cell wall of
      Saccharomyces cerevisiae is to activate immune cells. Here, we focused on the
      immunostimulation ability of S. cerevisiae itself to give this ability to
      fermented foods including yeast. Previously, we found that in S. cerevisiae the
      deletion of MCD4 gene causes exposure of beta-glucans on the cell surface and
      that the mcd4 deletion mutant strongly enhances immunity in vitro and in vivo.
      However, this is not a practical strain but a genetically modified strain with an
      antibiotic resistance gene, and growth was very slow. The aim of this study was
      to acquire a practical strain capable of strongly activating a macrophage. The
      parental strain y-21 was mutated with ethyl methanesulfonate, and the resulting
      strain was screened. Two mutants (AP-57 and AQ-37) were obtained. AQ-37 had the
      same fermentation capacity as y-21. In addition, a mutation point of AQ-37 was
      identified, suggesting that the mutation of NDD1 gene affects the cell wall
      structure and confers a high ability for macrophage stimulation. The obtained
      yeast may activate immune cells in materials to which the yeast is added. 

PMID- 24118944
TI  - Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety
      biomarkers for drug-induced liver injury in two human cohorts.
AB  - BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive
      biomarkers for drug-induced liver injury (DILI) than the gold standard used
      today, alanine aminotransferase (ALT). The aim of this study was to qualify novel
      DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate
      dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel
      biomarkers were measured by enzyme-linked immunosorbent assay or real-time
      quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a
      human volunteer study with acetaminophen and a human immunodeficiency virus
      (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and
      microRNA-122 levels were significantly increased at an earlier time point than
      ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the
      increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased
      after 1 week of treatment. In contrast to ALT, the novel biomarkers remained
      stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65
      and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to
      sensitivity and specificity.

PMID- 24118942
TI  - Re-annotation of the Saccharopolyspora erythraea genome using a systems biology
      approach.
AB  - BACKGROUND: Accurate bacterial genome annotations provide a framework to
      understanding cellular functions, behavior and pathogenicity and are essential
      for metabolic engineering. Annotations based only on in silico predictions are
      inaccurate, particularly for large, high G + C content genomes due to the lack of
      similarities in gene length and gene organization to model organisms. RESULTS:
      Here we describe a 2D systems biology driven re-annotation of the
      Saccharopolyspora erythraea genome using proteogenomics, a genome-scale metabolic
      reconstruction, RNA-sequencing and small-RNA-sequencing. We observed
      transcription of more than 300 intergenic regions, detected 59 peptides in
      intergenic regions, confirmed 164 open reading frames previously annotated as
      hypothetical proteins and reassigned function to open reading frames using the
      genome-scale metabolic reconstruction. Finally, we present a novel way of mapping
      ribosomal binding sites across the genome by sequencing small RNAs. CONCLUSIONS:
      The work presented here describes a novel framework for annotation of the
      Saccharopolyspora erythraea genome. Based on experimental observations, the 2D
      annotation framework greatly reduces errors that are commonly made when
      annotating large-high G + C content genomes using computational prediction
      algorithms.

PMID- 24118945
TI  - Metabolite profile of marine-derived endophytic Streptomyces sundarbansensis
      WR1L1S8 by liquid chromatography-mass spectrometry and evaluation of culture
      conditions on antibacterial activity and mycelial growth.
AB  - AIMS: This study was designed to investigate whether culture conditions (media,
      seawater concentration and pH) could lead Streptomyces sundarbansensis strain
      (isolated from marine brown algae Fucus sp. collected from Algerian coastline) to
      produce bioactive secondary metabolites. The most favourable condition for the
      production of anti-MRSA compound 1 [2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2
      yl)methyl)-2-propylchroman-4-one] was determined. METHODS AND RESULTS: The
      profile of metabolites present in the crude extracts was carried out by HPLC
      analysis equipped with a diode array detector evaporative light scattering
      detection (DAD-ELSD) or online coupled to electrospray ionization-mass
      spectrometry (ESI-MS). Compound 1 was the most abundant secondary metabolite by
      culturing the strains on starch casein agar (SCA) medium in freshwater or 50%
      seawater at pH 7 or 9 using agar-state fermentation method. CONCLUSIONS: The
      study has shown the efficiency of HPLC/ESI-MS technique in the analysis of
      polyketides produced by the strain under investigation. It was possible to
      establish the best culture conditions for obtaining the most bioactive compound
      1, previously isolated by the same strain. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Marine algae-actinobacteria associations are a particularly promising renewable
      system for the production of new antibacterial metabolites. Based on the
      promising bioactivity of the chemically characterized compound 1, the analytical
      methodology here applied has resulted as an effective approach for establishing
      its optimized production.

PMID- 24118946
TI  - New emergency department quality measure: from access block to National Emergency
      Access Target compliance.
AB  - OBJECTIVES: The study aims to investigate the effect of time of day and ED
      occupancy on the ability of EDs to admit or discharge patients within 4 h in
      accordance with the National Emergency Access Target (NEAT), and to compare this
      with corresponding levels of access block, the measure for ED performance before
      NEAT. METHODS: This is a retrospective analysis of 5 years of ED data from 30
      reporting public hospitals in Queensland, Australia. Relationships between these
      and variations in time of day and occupancy were explored using a Poisson
      generalised linear model. The main outcome measures are cases of NEAT non
      compliance (ED length of stay >4 h for all patients [i.e. admitted and non
      admitted] leaving the ED) and access block (ED length of stay >8 h for admitted
      patients). RESULTS: NEAT performance is found to be dependent on hospital size,
      and levels vary significantly for admitted and non-admitted patients. A higher
      proportion of patients breach NEAT during early mornings and low occupancy
      periods, a trend not observed with the previous access block metric. NEAT non
      compliance is also found to rise between 13.00 hours and 17.00 hours, a period
      when the proportion of access block cases typically drops. CONCLUSIONS: EDs face
      rising levels of NEAT non-compliance at times when corresponding access block
      levels have traditionally not been a concern. A higher proportion of patients
      breach the target during periods that would intuitively not be flagged as flow
      bottlenecks. The findings support the need for service level analysis and new
      solutions to guide workflow reform and maximise NEAT compliance.

PMID- 24118947
TI  - Ecology in the age of DNA barcoding: the resource, the promise and the challenges
      ahead.
AB  - Ten years after DNA barcoding was initially suggested as a tool to identify
      species, millions of barcode sequences from more than 1100 species are available
      in public databases. While several studies have reviewed the methods and
      potential applications of DNA barcoding, most have focused on species
      identification and discovery, and relatively few have addressed applications of
      DNA barcoding data to ecology. These data, and the associated information on the
      evolutionary histories of taxa that they can provide, offer great opportunities
      for ecologists to investigate questions that were previously difficult or
      impossible to address. We present an overview of potential uses of DNA barcoding
      relevant in the age of ecoinformatics, including applications in community
      ecology, species invasion, macroevolution, trait evolution, food webs and trophic
      interactions, metacommunities, and spatial ecology. We also outline some of the
      challenges and potential advances in DNA barcoding that lie ahead. 

PMID- 24118948
TI  - Electrocardiographic evaluation and degree of sedation with three doses of
      methadone in healthy dogs [corrected].
AB  - OBJECTIVE: The present study aimed to investigate the influence of methadone on
      cardiorespiratory parameters, electrocardiogram and clinical sedation in dogs.
      Further possible side effects are reported. STUDY DESIGN: Prospective
      experimental cross-over study. DOGS: Eight, 1-4-year-old, various breeds of dogs
      of both genders weighing 9-36 kg. METHODS: Each dog was treated three times:
      methadone 0.3 mg kg(-1) (M0.3), 0.5 mg kg(-1) (M0.5) and 1.0 mg kg(-1) (M1.0)
      intramuscularly. Respiratory rate, heart rate and arterial blood pressure were
      recorded as well as electrocardiographic evaluation of lead II. Clinical sedation
      in each treatment received a score (0-3) after drug administration and at 30
      minute intervals until scores and measurements returned to baseline values.
      RESULTS: A significant decrease in heart rate was seen with each dose of
      methadone and bradycardia (HR<60 bpm) was noted in a few dogs at each dose. A
      clinically significant arrhythmia occurred in one dog at 1 mg kg(-1) that
      required reversal with butorphanol. There was no significant difference in SAP,
      MAP and DAP between treatments. Some side effects such as salivation, defecation,
      vocalization and panting, after administration of methadone were observed. There
      were no differences in mean values of heart rate, P-wave and QRS complex duration
      and QT interval between treatments. CONCLUSION AND CLINICAL RELEVANCE: Methadone
      administration was associated with panting and a decrease in heart rate at all
      doses tested in this study. The cardiac rhythm should be monitored carefully in
      dogs when methadone is administered on its own, especially at higher doses.

PMID- 24118949
TI  - Control of methionine metabolism by the SahR transcriptional regulator in
      Proteobacteria.
AB  - Sulphur is an essential element in the metabolism. The sulphur-containing amino
      acid methionine is a metabolic precursor for S-adenosylmethionine (SAM), which
      serves as a coenzyme for ubiquitous methyltrtansferases. Recycling of organic
      sulphur compounds, e.g. via the SAM cycle, is an important metabolic process that
      needs to be tightly regulated. Knowledge about transcriptional regulation of
      these processes is still limited for many free-living bacteria. We identified a
      novel transcription factor SahR from the ArsR family that controls the SAM cycle
      genes in diverse microorganisms from soil and aquatic ecosystems. By using
      comparative genomics, we predicted SahR-binding DNA motifs and reconstructed SahR
      regulons in the genomes of 62 Proteobacteria. The conserved core of SahR regulons
      includes all enzymes required for the SAM cycle: the SAH hydrolase AhcY, the
      methionine biosynthesis enzymes MetE/MetH and MetF, and the SAM synthetase MetK.
      By using a combination of experimental techniques, we validated the SahR regulon
      in the sulphate-reducing Deltaproteobacterium Desulfovibrio alaskensis. SahR
      functions as a negative regulator that responds to the S-adenosylhomocysteine
      (SAH). The elevated SAH level in the cell dissociates SahR from its DNA operators
      and induces the expression of SAM cycle genes. The effector-sensing domain in
      SahR is related to SAM-dependent methylases that are able to tightly bind SAH.
      SahR represents a novel type of transcriptional regulators for the control of
      sulphur amino acid metabolism. 

PMID- 24118950
TI  - The impact of the BJUI and what influences it today: does impact factor matter?

PMID- 24118951
TI  - Urinary continence recovery after open and robot-assisted radical prostatectomy.

PMID- 24118952
TI  - Virtual prostate biopsy and biopsy simulation: lessons to be learned.

PMID- 24118953
TI  - Better late than early for long-term survival in patients with recurrence after
      renal carcinoma.

PMID- 24118954
TI  - Totally X-ray-free percutaneous nephrolithotomy: caveat emptor.

PMID- 24118955
TI  - HoLEP: is it coming of age?

PMID- 24118956
TI  - Generation (spark) gap: developments in lithotripsy.

PMID- 24118957
TI  - No one of us is as smart as all of us.

PMID- 24118958
TI  - Treatment efficacy and outcomes using a third generation shockwave lithotripter.
AB  - OBJECTIVES: To evaluate the clinical efficiency of a third generation
      electromagnetic shock wave lithotripter, the Lithoskop((r)) (Siemens, Erlangen,
      Germany), regarding outcomes, stone disintegration, retreatment and complication
      rates. To compare the results of the Lithoskop with other currently available
      systems and the reference standard lithotripter, the HM-3 (Dornier MedTech Europe
      GmbH, Wessling, Germany). PATIENTS AND METHODS: We analysed the data from 183
      patients, including 13 children, undergoing extracorporeal shock wave lithotripsy
      (ESWL) for renal and ureteric calculi collected from a prospectively populated
      database. Outcomes were assessed by plain abdominal film of kidney, ureter and
      bladder and renal ultrasonography for radiopaque and computerized tomography for
      radiolucent stones 1 day after treatment and after 3 months. We analysed stone
      size and location before and after treatment, stone disintegration rate,
      retreatment rate, stone-free and residual fragment rates after 3 months, along
      with auxiliary procedures and complications. RESULTS: The mean (range) patient
      age was 48.6 (1.3-81.4) years, including 13 children with a mean (range) age of
      8.4 (1.3-16.7) years, and 77% of the patients were male. In all, 46% of the
      calculi were localized in the kidney and 54% in the ureter. Renal stones were
      localized in the upper, middle and lower calyx and in the renal pelvis in 9, 29,
      30 and 32% of patients, respectively. Ureteric stones were localized in the
      upper, mid- and distal ureter in 29, 19 and 52% of patients, respectively. The
      median (range) stone size before ESWL was 10 (4-25) mm in the kidney and 8 (4-28)
      mm in the ureteric calculi. The overall stone-free rate after 3 months was 91%
      (88% for renal and 93% for ureteric calculi); the mean number of sessions to
      achieve these rates was 1.3. Stone-free rates and the required number of sessions
      were determined only by stone size. In 7.1% of the patients (n = 13) post
      interventional auxiliary procedures were necessary. We observed one perirenal
      haematoma as a major complication (0.5%), but this did not require any further
      therapy. CONCLUSIONS: Clinical stone-free rates with the Lithoskop are high and
      similar to those of other available systems, including the reference standard HM
      3 lithotripter. Retreatment and complication rates are low, supporting the use of
      ESWL as first-line therapy for urinary calculi <10 mm, independent of stone
      location.

PMID- 24118959
TI  - Penile disassembly: anatomical surgical steps.

PMID- 24118960
TI  - Fracture after androgen deprivation therapy among men with a high baseline risk
      of skeletal complications.

PMID- 24118961
TI  - Reply: To PMID 23035747.

PMID- 24118962
TI  - Randomized and prospective trial comparing tract creation using plasma
      vaporization with balloon dilatation in percutaneous nephrolithotomy.

PMID- 24118963
TI  - Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers.
AB  - BACKGROUND: Evidence is accumulating that a cannabis withdrawal syndrome is
      common, of clinical significance, and has a clear time course. Up till now, very
      limited data exist on the cannabis withdrawal symptoms in patients with co-morbid
      substance use disorders, other than cannabis use and tobacco use. METHODS:
      Symptoms of withdrawal were assessed through patient self-reports during
      detoxification in Danish residential rehabilitation centers. Patients (n = 90)
      completed booklets three times during their first month at the treatment centre.
      Self-reported withdrawal symptoms was rated using the DSM-5 Withdrawal Symptom
      Check List with withdrawal symptoms from all classes of substances, with no
      indication that the described symptoms should be attributed to withdrawal. Self
      reported time since last use of cannabis was used as a predictor of cannabis
      withdrawal severity. RESULTS: With the exception of loss of appetite, time since
      last use of cannabis was associated with all types of withdrawal symptoms listed
      in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other
      substances were related to time since last use of cannabis, including vivid,
      unpleasant dreams. CONCLUSIONS: The findings yield strong support to the notion
      of a cannabis withdrawal syndrome, and gives further evidence for the inclusion
      of the criterion of vivid, unpleasant dreams. Further, the findings speak against
      the significance of demand characteristics in determining the course of the
      symptoms of cannabis withdrawal.

PMID- 24118965
TI  - Connective Tissue Characteristics around Healing Abutments of Different
      Geometries: New Methodological Technique under Circularly Polarized Light.
AB  - PURPOSE: To describe contact, thickness, density, and orientation of connective
      tissue fibers around healing abutments of different geometries by means of a new
      method using coordinates. MATERIALS AND METHODS: Following the bilateral
      extraction of mandibular premolars (P2, P3, and P4) from six fox hound dogs and a
      2-month healing period, 36 titanium implants were inserted, onto which two groups
      of healing abutments of different geometry were screwed: Group A (concave
      abutments) and Group B (wider healing abutment). After 3 months the animals were
      sacrificed and samples extracted containing each implant and surrounding soft and
      hard tissues. Histological analysis was performed without decalcifying the
      samples by means of circularly polarized light under optical microscope and a
      system of vertical and horizontal coordinates across all the connective tissue in
      an area delimited by the implant/abutment, epithelium, and bone tissue. RESULTS:
      In no case had the connective tissue formed a connection to the healing
      abutment/implant in the internal zone; a space of 35 +/- 10 MUm separated the
      connective tissue fibers from the healing abutment surface. The total thickness
      of connective tissue in the horizontal direction was significantly greater in the
      medial zone in Group B than in Group A (p < .05). The orientation of the fibers
      varied according to the coordinate area so that internal coordinates showed a
      higher percentage of parallel fibers in Group A (p < .05) and a higher percentage
      of oblique fibers in Group B (p < .05); medial coordinates showed more oblique
      fibers (p < .05); and the area of external coordinates showed the highest
      percentage of perpendicular fibers (p < .05). The fiber density was higher in the
      basal and medial areas (p < .05). CONCLUSIONS: Abutment geometry influences the
      orientation of collagen fibers; therefore, an abutment with a profile wider than
      the implant platform favors oblique and perpendicular orientation of collagen
      fibers and greater connective tissue thickness.

PMID- 24118964
TI  - Measurement of social capital among clinical research trainees.
AB  - While physical and human capital are established as important predictors of
      success among early-career clinical investigators, less is known about the role
      of social capital. The authors aimed to develop a brief scale to assess social
      capital in this population and test its reliability and validity. A three-item
      assessment was developed based on a conceptual framework and measures of social
      capital from other fields and was administered to 414 clinical research trainees
      at the University of Pittsburgh in 2007-2012. The measure exhibited good internal
      consistency reliability (alpha = 0.71) and a normal distribution. On a 10-point
      scale, mean social capital was 6.4 (SD = 1.7). Social capital was significantly
      associated with 7 of the 9 expected constructs: sex, age, confidence in research
      skills, work-related motivation, burnout, and social support. Exploratory
      multivariable regression analysis demonstrated that social capital was most
      strongly associated with higher research confidence (beta = 0.35, p < 0.001),
      higher extrinsic motivation (beta = 0.50, p = 0.003), and lower burnout (ptrend =
      0.02). This three-item scale measures social capital in this population with
      adequate internal consistency reliability, face validity, and construct validity.
      This brief assessment provides a tool that may be valuable to benchmark social
      capital of clinical research trainees and to better contextualize programmatic
      and trainee outcomes. 

PMID- 24118966
TI  - Antimicrobial activity of short- and medium-term applications of
      polyhexamethylene biguanide, chlorhexidine digluconate and calcium hydroxide in
      infected immature bovine teeth in vitro.
AB  - AIM: To compare the antimicrobial activity of polyhexamethylene biguanide
      (Prontosan wound gel, Pr) and chlorhexidine digluconate (CHX) after short- and
      medium-term application with the disinfection ability of calcium hydroxide (Ca)
      in a model using immature bovine teeth. METHODS: Sixty immature bovine roots were
      infected with Enterococcus faecalis and randomly assigned to six groups (n = 10).
      Disinfectants were applied into the root canal for 10 min (CHX-10 min and Pr-10
      min) or 7 days (CHX-7d, Pr-7d and Ca-7d(g) ). In the negative control group (Co
      n), no disinfectant was used. Dentine samples were collected, and the total count
      of bacteria and colony-forming units were determined. The log10 -transformed
      Colony-forming units (CFU) data were analysed using a Kruskal-Wallis test with
      post hoc Wilcoxon multiple-comparison tests. RESULTS: The application of
      disinfectants led to a significant reduction in CFUs in all groups compared with
      group Co-n. When compared to Ca-7d(g) , CHX-7d (P = 0.290), CHX-10 min (P =
      0.963) and Pr-7d (P = 0.095) revealed no significant differences. Pr-10 min had a
      significantly higher CFU value than Ca-7d(g) (P = 0.0004), CHX-10 min (P =
      0.0009) and Pr-7d (P = 0.0006). CONCLUSIONS: Within the limitations of this
      study, sufficient antimicrobial effect may be reached by a short-term application
      of CHX. For the application of 1% Prontosan wound gel, a medium-term use (7 day)
      is required, while short-term use (10 min) is less effective.

PMID- 24118967
TI  - Highlights of melanoma research presented at the 49th annual meeting of the
      American Society of Clinical Oncology in Chicago, 2013.

PMID- 24118968
TI  - Relationship between adhesion molecules and virological response to pegylated
      interferon-alpha-2a treatment in patients with chronic hepatitis B: A pilot
      study.
AB  - AIM: We performed a clinical study to investigate potential association between
      serum levels of soluble adhesion molecules and virological response to pegylated
      interferon-alpha-2a (PEG IFN-alpha-2a) treatment in patients with chronic
      hepatitis B (CHB). METHODS: Thirty-two patients with chronic hepatitis B virus
      genotype B were recruited in this study, who were treated with PEG IFN-alpha-2a
      180 MUg every week and then followed up for 24 weeks. Thirty healthy control
      subjects were recruited from volunteer blood donors. Serum concentrations of
      soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell
      adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble L
      selectin (sL-selectin) in patients were investigated by enzyme-linked immunoassay
      before and after treatment. RESULTS: Serum concentrations of sICAM-1, sVCAM-1, sE
      selectin and sL-selectin in CHB patients were significantly higher compared to
      the control group before treatment (P < 0.00001, respectively). In CHB patients
      responding to the PEG IFN-alpha-2a treatment, serum levels of sICAM-1, sVCAM-1,
      sE-selectin and sL-selectin were higher than those in non-responders before
      treatment (PI  = 0.001, PV  = 0.002, PE  = 0.02, PL  = 0.004). The levels of
      sICAM-1, sVCAM-1, sE-selectin and sL-selectin decreased in virological responders
      of treatment at 12 and 24 weeks (PI  = 0.0001, PV  = 0.00004, PE  = 0.002, PL  =
      0.0004; PI  = 0.00007, PV  = 0.00001, PE  = 0.0003, PL  = 0.00003), while no
      obvious changes were observed in non-responders (P > 0.05, respectively).
      CONCLUSION: Results obtained indicated increased levels of sICAM-1, sVCAM-1, sE
      selectin and sL-selectin could be related to virological response to PEG IFN
      alpha-2a treatment in CHB patients, and have a prognostic effect on virological
      response.

PMID- 24118969
TI  - Influence of betaS allele in the lipid peroxidation and antioxidant capacity
      parameters.
AB  - INTRODUCTION: The oxidative process plays a fundamental role in the
      pathophysiology of sickle cell anemia (SCA), and population and environmental
      characteristics may influence redox balance. The aim of this study was to
      evaluate lipid peroxidation and antioxidant capacity in Brazilian Hb S carriers
      undergoing different therapies. METHODS: Blood samples from 270 individuals were
      analyzed (Hb SS, n = 68; Hb AS, n = 53, and Hb AA, n = 149). Hemoglobin genotypes
      were assessed through cytological, electrophoretic, chromatographic, and
      molecular methods. Plasma lipid peroxidation and antioxidant capacity were
      measured by spectrophotometric methods. RESULTS: Patients with SCA who used iron
      chelating drugs combined with hydroxyurea, associated with regular transfusions,
      showed lower levels of TBARS (P <= 0.05), higher levels of TEAC (P <= 0.01), and
      lower TBARS/TEAC ratio (R = 255.8). The redox profile of Hb AS subjects was not
      statistically different (P > 0.05) from that of Hb AA subjects. CONCLUSION: The
      data suggest that oxidative stress is lower in the patients with SCA who received
      regular blood transfusions associated with the combined use of HU and iron
      chelators than the group received only HU. The redox system of the Hb AS carriers
      is compatible with the control group.

PMID- 24118970
TI  - Early case-fatality rates in elderly stroke patients do not increase when age
      increases.
AB  - AIM: We studied the association between age and survival after stroke. We
      particularly focused on deaths that could be attributed to the stroke lesion
      itself; that is, early death in severe stroke. METHODS: A registry of all
      hospitalized stroke patients in Denmark included 93897 patients with information
      on stroke severity (Scandinavian Stroke Scale [SSS] 0-58), computed tomography,
      cardiovascular risk, age, sex and fatality within 1 month. Using regression
      models, we constructed age trajectories of 3-days, 1-week, and 1-month case
      fatality rates unadjusted and adjusted for stroke severity, sex, and
      cardiovascular risk factors for patients with SSS <25 and SSS >= 25. RESULTS: The
      3-days, 1-week, and 1-month case-fatality were 3.6%, 5.8% and 10.3%,
      respectively. Age-trajectories (SSS <25): 3-days case-fatality rates increased to
      the age of 75 years. Case-fatality rates then declined (unadjusted model) or
      leveled off (adjusted model) as age increased. One-week case-fatality increased
      to the age of 85 years. Case-fatality then leveled off (unadjusted model) or
      continued to rise (adjusted model) as age increased. One-month case-fatality
      rates increased throughout the entire lifespan. Age-trajectories (SSS >= 25): the
      leveling off phenomenon was still present for 3-days case-fatality; however, it
      was less pronounced. CONCLUSIONS: Very early stroke case-fatality rates
      increasing to the age of 75-85 years subsequently leveled off or even declined
      with increasing age. Advanced age per se should not be seen as a disadvantage in
      terms of surviving stroke in the very acute phase.

PMID- 24118971
TI  - Dynamic proteins: changes in structures, activities and networks.
AB  - The minireview series represents a sampling of work presented at the 2012 Methods
      in Protein Structure Analysis meeting held in Ottawa, Canada. Within the 11
      minireviews are methods for studying proteins in vitro and within the context of
      the cell. This series offers a window into the dynamics of protein conformation,
      regulation, and function.

PMID- 24118972
TI  - A pilot study to compare daily with twice weekly transcutaneous posterior tibial
      nerve stimulation for faecal incontinence.
AB  - AIM: Posterior tibial nerve stimulation (PTNS) has been shown to improve faecal
      incontinence in the short term. The optimal treatment regimen is unclear with
      wide variations in protocol reported in the literature. The study aimed to assess
      two different regimens of transcutaneous PTNS and to establish whether increasing
      the frequency of stimulation increases the effectiveness. METHOD: Thirty patients
      were randomized to receive once daily or twice weekly PTNS for a 6-week period.
      The treatment was carried out by the patient at home after instruction. The
      primary investigator was blinded to the patient allocation until the study had
      ended, at which point the symptoms were assessed. No further stimulation was
      given after 6 weeks and the patients were followed until their symptoms returned
      to the pre-stimulation state (baseline). The primary outcome measure was a change
      in the frequency of incontinent episodes. RESULTS: Three patients in the daily
      group and none in the twice weekly group achieved complete continence. Only
      patients from the daily group showed a significant reduction in median
      (interquartile range) incontinent episodes per week from 5 (11.13) to 3.5 (4.31)
      (P = 0.025). There was no significant change in the frequency of defaecation nor
      in the ability to defer defaecation. Patients in the daily group experienced a
      significant improvement in the domains of lifestyle [2.2 (1.7) to 2.6 (1.65), P =
      0.04] and embarrassment [1.7 (0.85) to 2.15 (0.4), P = 0.04] on the Rockwood
      Fecal Incontinence Quality of Life assessment. No adverse events were reported.
      CONCLUSION: Transcutaneous PTNS can safely be used by the patient at home. Daily
      treatment may be more effective than twice weekly treatment. Larger studies are
      needed to investigate this further.

PMID- 24118973
TI  - Non-post-transplant lymphoproliferative disorder cancers in children after organ
      transplantation.

PMID- 24118974
TI  - Specialty of prescribers associated with prescription opioid fatalities in Utah,
      2002-2010.
AB  - Opioid adverse events are widespread, and deaths have been directly attributed to
      opioids prescribed by medical professionals. Little information exists on the
      amount of opioids various medical specialties prescribe and the opioid fatality
      rate that would be expected if prescription opioid-related deaths were
      independent of medical specialty. OBJECTIVE: To compute the incidence of
      prescription opioid fatalities by medical specialty in Utah and to calculate the
      attributable risk (AR) of opioid fatality by medical specialty. DESIGN:
      Prevalence database study design linking the Utah Controlled Substance Database
      (CSD) for prescribing data with the Utah Medical Examiner data to identify
      prescription opioid fatalities. AR were calculated for each medical specialty and
      year. RESULTS: Opioid prescriptions are common with 23,302,892 recorded in the
      CSD for 2002-2010, 0.64% of which were associated with a fatality. We attached
      specialty to 90.2% of opioid prescriptions. Family medicine and internal medicine
      physicians wrote the largest proportion of prescriptions (24.1% and 10.8%) and
      were associated with the greatest number of prescription opioid fatalities. The
      number of active prescriptions at time of death decreased each year. The AR of
      fatality by provider specialty varied each year with some specialties, such as
      pain medicine and anesthesiology, consistently associated with more fatalities
      per 1,000 opioid prescriptions than internal medicine physicians the same year.
      CONCLUSIONS: Primary care providers were the most frequent prescribers and the
      most often associated with opioid fatalities and should be targeted for education
      about safe prescribing along with specialties that prescribe less frequently but
      are associated with a positive AR for opioid fatality.

PMID- 24118975
TI  - Improving prokaryotic transposable elements identification using a combination of
      de novo and profile HMM methods.
AB  - BACKGROUND: Insertion Sequences (ISs) and their non-autonomous derivatives
      (MITEs) are important components of prokaryotic genomes inducing duplication,
      deletion, rearrangement or lateral gene transfers. Although ISs and MITEs are
      relatively simple and basic genetic elements, their detection remains a difficult
      task due to their remarkable sequence diversity. With the advent of high
      throughput genome and metagenome sequencing technologies, the development of
      fast, reliable and sensitive methods of ISs and MITEs detection become an
      important challenge. So far, almost all studies dealing with prokaryotic
      transposons have used classical BLAST-based detection methods against reference
      libraries. Here we introduce alternative methods of detection either taking
      advantages of the structural properties of the elements (de novo methods) or
      using an additional library-based method using profile HMM searches. RESULTS: In
      this study, we have developed three different work flows dedicated to ISs and
      MITEs detection: the first two use de novo methods detecting either repeated
      sequences or presence of Inverted Repeats; the third one use 28 in-house
      transposase alignment profiles with HMM search methods. We have compared the
      respective performances of each method using a reference dataset of 30 archaeal
      and 30 bacterial genomes in addition to simulated and real metagenomes. Compared
      to a BLAST-based method using ISFinder as library, de novo methods significantly
      improve ISs and MITEs detection. For example, in the 30 archaeal genomes, we
      discovered 30 new elements (+20%) in addition to the 141 multi-copies elements
      already detected by the BLAST approach. Many of the new elements correspond to
      ISs belonging to unknown or highly divergent families. The total number of MITEs
      has even doubled with the discovery of elements displaying very limited sequence
      similarities with their respective autonomous partners (mainly in the Inverted
      Repeats of the elements). Concerning metagenomes, with the exception of short
      reads data (<300 bp) for which both techniques seem equally limited, profile HMM
      searches considerably ameliorate the detection of transposase encoding genes (up
      to +50%) generating low level of false positives compare to BLAST-based methods.
      CONCLUSION: Compared to classical BLAST-based methods, the sensitivity of de novo
      and profile HMM methods developed in this study allow a better and more reliable
      detection of transposons in prokaryotic genomes and metagenomes. We believed that
      future studies implying ISs and MITEs identification in genomic data should
      combine at least one de novo and one library-based method, with optimal results
      obtained by running the two de novo methods in addition to a library-based
      search. For metagenomic data, profile HMM search should be favored, a BLAST-based
      step is only useful to the final annotation into groups and families.

PMID- 24118976
TI  - Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed
      treatment comparison of fixed-length and response-guided treatment regimens in
      treatment-naive and -experienced patients.
AB  - BACKGROUND: Telaprevir (TVR) has been approved for response-guided-therapy (RGT)
      of chronic hepatitis C (HCV) genotype-1-infection in treatment-naive and 
      experienced patients. In RGT-regimens patients that did not achieve extended
      rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment
      for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a
      fixed-duration regardless of their RVR. METHODS: This systematic review and
      Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and
      safety of standard-therapy with pegylated-interferon-alpha/ribavirin (Peg-IFN
      alpha/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-alpha/RBV for 12 weeks with
      a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN
      alpha/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-alpha/RBV followed by
      12 weeks of Peg-IFN-alpha/RBV (group D) or no therapy (group E). RESULTS: We
      identified seven randomized controlled trials including 3505 patients. Compared
      to standard-treatment (group A), treatment-naive patients allocated to groups B,
      C, and D were significantly more likely to achieve sustained-virological-response
      (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A
      3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients
      achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0
      13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)).
      Patients treated with short RGT (simulated group E) did also have a significant
      improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6
      8.2)), whereas the effect was not significant in treatment-naive patients (OR E
      vs. A 1.6 (CrI 0.9-2.7)). CONCLUSION: Long FLT and RGT regimens are useful
      treatment options for HCV-genotype-1 in both treatment-naive and -experienced
      patients. A short 24-weeks FLT regimen does not seem to be inferior and should
      further be evaluated in clinical trials to reduce side effects and costs of
      treatment.

PMID- 24118977
TI  - A psychosocial risk index for poor glycemic control in children and adolescents
      with type 1 diabetes.
AB  - OBJECTIVE: The aim of this study was to develop and validate a psychosocial
      screening tool to predict risk for poor glycemic control in children with type 1
      diabetes. METHODS: Participants seen for psychological screening were 196
      children aged 3-18 yr at diabetes diagnosis. A psychosocial risk index was
      developed to predict poor glycemic control [mean hemoglobin A1c (HbA1c) >= 9.5%;
      80 mmol/mol] 1-4 yr post diagnosis. Cutoff scores were derived for multiple
      levels of risk from receiver operating characteristic (ROC) curves and likelihood
      ratios (LRs). Discrimination and calibration were examined in the sample, and
      validated in 1000 bootstrap samples. Ability to predict diabetes-related
      emergency-room (ER) visits and diabetic ketoacidosis (DKA) was also tested.
      RESULTS: The risk index accounted for 16.2% of variance in mean HbA1c,
      discriminated between children with and without poor glycemic control [area under
      the receiver operating characteristic curve (AUC) = 0.814, 0.713-0.915; p <
      0.001], ER visits (AUC = 0.655, 0.561-0.748; p = 0.001), and DKA(AUC = 0.709,
      0.588-0.830; p = 0.001), and was well-calibrated. Every one-point increase in
      score was associated with an absolute increase in risk for poor glycemic control
      of approximately 10% (LRs = 1.7, 3.2, 5.8, and 9.3). Sensitivity and specificity
      were 0.68 (0.43-0.86) and 0.79 (0.72-0.84) for detecting patients at moderate
      risk, and 0.53 (0.29-0.75) and 0.91 (0.85-0.95) for detecting high-risk patients.
      The index performed equally well in validation samples. CONCLUSIONS: This paper
      presents the first psychosocial risk index for poor glycemic control in children
      newly diagnosed with type 1 diabetes. It is brief, easily administered, and
      provides a single score that translates directly into an estimate of risk that
      can help guide routine diabetes care.

PMID- 24118978
TI  - Bioweathering of nontronite colloids in hybrid silica gel: implications for iron
      mobilization.
AB  - AIMS: This study aimed to study biotic iron dissolution using a new hybrid
      material constituted of well-dispersed mineral colloids in a silica gel matrix.
      This permitted to prevent adsorption of colloidal mineral particles on bacteria.
      Hybrid silica gel (HSG) permitted to study bioweathering mechanisms by diffusing
      molecules. METHODS AND RESULTS: Hybrid silica gel was synthesized through a
      classical sol-gel procedure in which mineral colloidal particles (NAu-2) were
      embedded in a porous silica matrix. Rahnella aquatilis RA1, isolated from a wheat
      rhizosphere was chosen for its ability to dissolve minerals by producing various
      organic acids and siderophores. Pyruvic, acetic and lactic acids were the major
      organic acids produced by R. aquatilis RA1 followed by oxalic and citric acids at
      the end of incubation. Comparison of abiotic and biotic experiments revealed a
      high efficiency of R. aquatilis RA1 for iron dissolution suggesting an optimized
      action of different ligands that solubilized or mobilized iron. CONCLUSIONS:
      Hybrid silica gel allowed focusing on the colloidal mineral weathering by
      metabolites diffusion without mineral adsorption on bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Hybrid silica gels are new and efficient tools to study
      colloidal mineral bioweathering. Adjusting HSG porosity and hydrophobicity should
      permit to precise the influence of limiting diffusion of siderophores or
      aliphatic organic acids on mineral weathering.

PMID- 24118980
TI  - Impact of prostate cancer on sexual relationships: a longitudinal perspective on
      intimate partners' experiences.
AB  - INTRODUCTION: In this prospective study of localized prostate cancer patients and
      their partners, we analyzed how partner issues evolve over time, focusing on
      satisfaction with care, influence of cancer treatment, and its impact on
      relationship with patient, cancer worry, and personal activities. AIMS: Our study
      aims were twofold: (i) to determine whether the impact of treatment on patients
      and partners moderate over time and (ii) if receiving surgery (i.e., radical
      prostatectomy) influences partner issues more than other treatments. METHODS:
      Patients newly diagnosed with localized prostate cancer and their female partners
      were recruited from three states to complete surveys by mail at three time points
      over 12 months. MAIN OUTCOME MEASURES: The four primary outcomes assessed in the
      partner analysis included satisfaction with treatment, cancer worry, and the
      influence of cancer and its treatment on their relationship (both general
      relationship and sexual relationship). RESULTS: This analysis included 88 patient
      partner pairs. At 6 months, partners reported that cancer had a negative impact
      on their sexual relationship (39%--somewhat negative and 12%--very negative). At
      12 months, this proportion increased substantially (42%--somewhat negative and
      29%--very negative). Partners were significantly more likely to report that their
      sexual relationship was worse when the patient reported having surgery (P =
      0.0045, odds ratio = 9.8025, 95% confidence interval 2.076-46.296). A minority of
      partners reported significant negative impacts in other areas involving their
      personal activities (16% at 6 months and 25% at 12 months) or work life (6% at 6
      months, which increased to 12% at 12 months). CONCLUSION: From partners'
      perspectives, prostate cancer therapy has negative impact on sexual relationships
      and appears to worsen over time.

PMID- 24118979
TI  - Evaluation of 11 single-locus and seven multilocus DNA barcodes in Lamium L.
      (Lamiaceae).
AB  - The aim of this work was to evaluate the suitability of selected DNA regions in
      the barcoding of plants, based on the species belonging to the genus Lamium
      (Lamiaceae). For this purpose, nine chloroplast barcodes, that is, accD, matK,
      rbcL, rpoA, rpoB, rpoC1, rpoC2, trnH-psbA, trnL-trnF, as well as ITS nuclear
      region, and intron of mitochondrial nad5 gene were tested. Among the single-locus
      barcodes, most effective in the identification of Lamium species was the trnH
      psbA spacer and matK gene. The high level of variability and resolving power was
      also observed in the case of rpoA and rpoC2 genes. Despite the high interspecies
      variability of ITS region, it turned out to be inapplicable in Lamium
      identification. An important disadvantage of ITS as a barcode is a limitation of
      its use in polyploid plants, samples contaminated with fungal material or samples
      with partially degraded DNA. We have also evaluated five-two-locus and two-three
      locus barcode regions created from a combination of most effective single loci.
      The best-performing barcode combinations were matK + trnH-psbA and matK + rpoA.
      Both of them had equally high discriminative power to identify Lamium species. 

PMID- 24118981
TI  - A school-based program implemented by community providers previously trained for
      the prevention of eating and weight-related problems in secondary-school
      adolescents: the MABIC study protocol.
AB  - BACKGROUND: The prevention of eating disorders and disordered eating are
      increasingly recognized as public health priorities. Challenges in this field
      included moving from efficacy to effectiveness and developing an integrated
      approach to the prevention of a broad spectrum of eating and weight-related
      problems. A previous efficacy trial indicated that a universal disordered eating
      prevention program, based on the social cognitive model, media literacy
      educational approach and cognitive dissonance theory, reduced risk factors for
      disordered eating, but it is unclear whether this program has effects under more
      real-world conditions. The main aim of this effectiveness trial protocol is to
      test whether this program has effects when incorporating an integrated approach
      to prevention and when previously-trained community providers implement the
      intervention. METHODS/DESIGN: The research design involved a multi-center non
      randomized controlled trial with baseline, post and 1-year follow-up measures.
      Six schools from the city of Sabadell (close to Barcelona) participated in the
      intervention group, and eleven schools from four towns neighboring Sabadell
      participated in the control group. A total of 174 girls and 180 boys in the
      intervention group, and 484 girls and 490 boys in the control group were
      registered in class lists prior to baseline. A total of 18 community providers,
      secondary-school class tutors, nurses from the Catalan Government's Health and
      School Program, and health promotion technicians from Sabadell City Council were
      trained and delivered the program. Shared risk factors of eating and weight
      related problems were assessed as main measures. DISCUSSION: It will be vital for
      progress in disordered eating prevention to conduct effectiveness trials, which
      test whether interventions are effective when delivered by community providers
      under ecologically valid conditions, as opposed to tightly controlled research
      trials. The MABIC project will provide new contributions in this transition from
      efficacy to effectiveness and new data about progress in the integrated approach
      to prevention. Pending the results, the effectiveness trial meets the
      effectiveness standards set down by the Society for Prevention Research. This
      study will provide new evidence to improve and enhance disordered eating
      prevention programs. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN47682626.

PMID- 24118983
TI  - Paracoccidioides brasiliensis PbP27 gene: knockdown procedures and functional
      characterization.
AB  - Paracoccidioides brasiliensis PbP27 gene encodes a protein localized in both the
      fungal cytoplasm and cell wall. The parasitic infectious form produces this
      protein preferentially with the gene's expression varying between the fungus
      phylogenetic species. The biological function of the native p27 has yet to be
      determined during either growth of the yeast or host infection. Therefore, in
      this study, through the use of antisense RNA technology and Agrobacterium
      tumefaciens-mediated transformation, we generated mitotically stable PbP27
      mutants (PbP27 aRNA) with the goal to evaluate the role of p27 in the biology and
      virulence of this fungus. PbP27 expression was reduced 60-75% in mutants, as
      determined by real-time PCR in correlation with a decrease in p27 expression. No
      alterations in the growth curve or in the ability to shift from mycelia to yeast
      or from yeast to mycelia were observed in PbP27 aRNA strains; however, we did
      observe a reduction in cell vitality. Moreover, a decrease in cell viability of
      PbP27 aRNA yeast cells after interaction with IFN-gamma-stimulated macrophages
      was detected. Based on these results, we propose that p27 plays a role in yeast
      cell architecture and represents one of the mechanisms employed by this fungus
      for its interaction with the monocyte/macrophage system. 

PMID- 24118982
TI  - Factor XI anion-binding sites are required for productive interactions with
      polyphosphate.
AB  - BACKGROUND: Conversion of factor XI (FXI) to FXIa is enhanced by polymers of
      inorganic phosphate (polyP). This process requires FXI to bind to polyP. Each
      FXIa subunit contains anion-binding sites (ABSs) on the apple 3 (A3) and
      catalytic domains that are required for normal heparin-mediated enhancement of
      FXIa inhibition by antithrombin. AIMS: To determine the importance of FXI ABSs to
      polyP enhancement of FXI activation. METHODS: Recombinant FXI variants lacking
      one or both ABSs were tested in polyP-dependent purified protein systems, plasma
      clotting assays, and a murine thrombosis model. RESULTS: In the presence of
      polyP, activation rates for FXI lacking either ABS were reduced compared with
      wild-type FXI, and FXI lacking both sites had an even greater defect. In contrast
      to heparin, polyP binding to FXIa did not enhance inhibition by antithrombin and
      did not interfere with FXIa activation of FIX. FXI lacking one or both ABSs does
      not reconstitute FXI-deficient plasma as well as wild-type FXI when polyP was
      used to initiate coagulation. In FXI-deficient mice, FXI lacking one or more ABSs
      was inferior to wild-type FXI in supporting arterial thrombus formation.
      CONCLUSIONS: The ABSs on FXIa that are required for expression of heparin's
      cofactor activity during protease inhibition by antithrombin are also required
      for expression of polyP cofactor activity during FXI activation. These sites may
      contribute to FXI-dependent thrombotic processes.

PMID- 24118984
TI  - Clinical research priorities in emergency medicine.
AB  - OBJECTIVE: To determine the clinical research priorities of Fellows of the
      Australasian College for Emergency Medicine (ACEM) in order to inform the
      strategic research agenda specific to multicentre clinical research. METHODS: An
      anonymous survey of all ACEM Fellows (FACEMs) listed on the ACEM researcher
      database was conducted between January and March 2013. RESULTS: Of 108 FACEMs
      invited to participate, 54 (50%) responded. Over half of respondents (61%) had a
      higher research degree but only a minority (24%) had funded research positions.
      The top research categories identified as priorities were resuscitation, trauma,
      cardiology, ED ultrasound, acute behavioural disturbance and geriatrics. The most
      common specific sub-categories included anterior chest pain, fluid resuscitation
      in trauma, and drug therapy for both atrial fibrillation and acute behavioural
      disturbance. Several specific research questions related to chest pain,
      resuscitation/sepsis, stroke, paediatrics and pulmonary embolus. CONCLUSION: The
      findings provide guidance and support for research areas amenable to
      collaborative multicentre clinical research within emergency medicine. Discussion
      rounds are planned to translate these perceived research priorities to actual
      priorities.

PMID- 24118985
TI  - Coenzyme Q in pregnant women and rats with intrahepatic cholestasis.
AB  - BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy is a high-risk liver
      disease given the eventual deleterious consequences that may occur in the foetus.
      It is accepted that the abnormal accumulation of hydrophobic bile acids in
      maternal serum are responsible for the disease development. Hydrophobic bile
      acids induce oxidative stress and apoptosis leading to the damage of the hepatic
      parenchyma and eventually extrahepatic tissues. As coenzyme Q (CoQ) is considered
      an early marker of oxidative stress in this study, we sought to assess CoQ
      levels, bile acid profile and oxidative stress status in intrahepatic
      cholestasis. METHODS: CoQ, vitamin E and malondialdehyde were measured in plasma
      and/or tissues by HPLC-UV method whereas serum bile acids by capillary
      electrophoresis in rats with ethinyl estradiol-induced cholestasis and women with
      pregnancy cholestasis. RESULTS: CoQ and vitamin E plasma levels were diminished
      in both rats and women with intrahepatic cholestasis. Furthermore, reduced CoQ
      was also found in muscle and brain of cholestatic rats but no changes were
      observed in heart or liver. In addition, a positive correlation between CoQ and
      ursodeoxycholic/lithocholic acid ratio was found in intrahepatic cholestasis
      suggesting that increased plasma lithocholic acid may be intimately related to
      CoQ depletion in blood and tissues. CONCLUSION: Significant CoQ and vitamin E
      depletion occur in both animals and humans with intrahepatic cholestasis likely
      as the result of increased hydrophobic bile acids known to produce significant
      oxidative stress. Present findings further suggest that antioxidant
      supplementation complementary to traditional treatment may improve cholestasis
      outcome.

PMID- 24118986
TI  - Contemporary epidemiology of gout and hyperuricemia in community elderly in
      Beijing.
AB  - AIM: To evaluate the prevalence and risk factors of gout and hyperuricemia in an
      elderly community cohort in Beijing. METHOD: A total of 10 039 individuals aged
      50 years or older participated in the study, based on the Beijing Longitudinal
      Study on Aging II (BLSA II) Cohort in 2009. All participants were asked for a
      Gout Assessment Questionnaire under the guidelines of the American College of
      Rheumatology. The prevalence of gout and hyperuricemia were evaluated. The
      potential risk factors for gout and hyperuricemia were analyzed by logistic
      regression. RESULTS: In our BLSA II cohort, the prevalence of gout and
      hyperuricemia were 2.8% and 18.1%, respectively. The prevalence of gout in the
      Han population was significantly lower than that in Hui population (2.6% vs.
      5.8%). The traditional risk factors (age and body mass index [BMI] and metabolic
      syndrome [ms]) were significantly associated with the risk of gout and
      hyperuricemia (age: OR 1.2, 95%CI 1.1-1.5 for gout; OR 1.3, 95%CI 1.1-1.4 for
      hyperuricemia, respectively; BMI: OR 1.6, 95%CI 1.3-2.0; OR 1.5, 95%CI 1.3-1.8;
      ms: OR 2.6, 95%CI 2.0-3.3; OR 2.0, 95%CI 1.7-2.2). Family history was strongly
      associated with an increased risk of gout (OR 6.5, 95%CI 3.9-10.8). CONCLUSION:
      Our study showed that the prevalence of both gout and hyperuricemia in Beijing
      remains substantial. The prevalence in the Hui population was higher than other
      ethnic groups. The traditional risk factors were strong risk factors for gout and
      hyperuricemia in China.

PMID- 24118987
TI  - Metabolic versatility of toluene-degrading, iron-reducing bacteria in tidal flat
      sediment, characterized by stable isotope probing-based metagenomic analysis.
AB  - DNA stable isotope probing and metagenomic sequencing were used to assess the
      metabolic potential of iron-reducing bacteria involved in anaerobic aromatic
      hydrocarbon degradation in oil spill-affected tidal flats. In a microcosm
      experiment, (13) C-toluene was degraded with the simultaneous reduction of
      Fe(III)-NTA, which was also verified by quasi-stoichiometric (13) C-CO2 release.
      The metabolic potential of the dominant member affiliated with the genus
      Desulfuromonas in the heavy DNA fraction was inferred using assembled scaffolds
      (designated TF genome, 4.40 Mbp with 58.8 GC mol%), which were obtained by
      Illumina sequencing. The gene clusters with peripheral pathways for toluene and
      benzoate conversion possessed the features of strict and facultative anaerobes.
      In addition to the class II-type benzoyl-CoA reductase (Bam) of strict anaerobes,
      the class I-type (Bcr) of facultative anaerobes was encoded. Genes related to the
      utilization of various anaerobic electron acceptors, including iron, nitrate (to
      ammonia), sulfur and fumarate, were identified. Furthermore, genes encoding
      terminal oxidases (caa3 , cbb3 and bd) and a diverse array of genes for oxidative
      stress responses were detected in the TF genome. This metabolic versatility may
      be an adaptation to the fluctuating availability of electron acceptors and donors
      in tidal flats.

PMID- 24118988
TI  - Salivary epithelial cells as model to study immune response against cutaneous
      pathogens.
AB  - The human skin not only provides passive protection as a physical barrier against
      external injury, but also mediates active surveillance via epidermal cell surface
      receptors that recognize and respond to potential invaders. Primary keratinocytes
      and immortalized cell lines, the commonly used sources to investigate immune
      responses of cutaneous epithelium are often difficult to obtain and/or
      potentially exhibit changes in cellular genetic make-up. Here we investigated the
      possibility of using salivary epithelial cells (SEC) to evaluate the host
      response to cutaneous microbes. Elevated secretion of IFN-gamma and IL-12 was
      observed in the SEC stimulated with Staphylococcus aureus, a transient pathogen
      of the skin, as mono species biofilm as compared to SEC stimulated with a
      commensal microbe, the Staphylococcus epidermidis. Co-culture of the SEC with
      both microbes as dual species biofilm elicited maximum cytokine response.
      Stimulation with S. aureus alone but not with S. epidermidis alone induced
      maximum toll-like receptor-2 (TLR-2) expression in the SEC. Exposure to dual
      species biofilm induced a sustained upregulation of TLR-2 in the SEC for up to an
      hour. The data support novel application of the SEC as efficient biospecimen that
      may be used to investigate personalized response to cutaneous microflora. 

PMID- 24118989
TI  - Depression in young adult psychiatric outpatients: delimiting early onset.
AB  - AIM: The aim of this study was to examine differences in childhood, adolescent
      and adult onset of depression. METHODS: Young psychiatric outpatients (n = 156)
      diagnosed with a lifetime depressive episode were divided into three groups
      according to age of onset of their first depressive episode: childhood (<=12
      years, n = 21), adolescent (13-17 years, n = 58) and early adult onset (18-25
      years, n = 77). Participants were assessed by diagnostic interviews and by
      questionnaires measuring previous life events and childhood developmental delays.
      Clinical characteristics and various risk factors were compared between groups.
      RESULTS: This clinical sample was dominated by women, with onset of their first
      depressive episode occurring during adolescence. Childhood onset was related to
      an increased number of depressive episodes, higher prevalence of personality
      disorders, more current social problems and more reported development delays
      during childhood regarding literacy learning, social skills and memory. They also
      reported more separation anxiety symptoms and neglect during childhood and more
      experiences of teenage pregnancies and abortions. CONCLUSIONS: Childhood onset of
      depression is associated with more severe symptoms, more psychosocial risk
      factors and childhood developmental delays. Because all onset groups shared many
      features, the results are inconclusive if there are distinct subgroups according
      to age of onset.

PMID- 24118990
TI  - Management of crown-related fractures in children: an update review.
AB  - Traumatic dental injuries (TDIs) are a serious public health problem.
      Epidemiology of dental trauma indicates that these injuries are more prevalent in
      child population of the world. Children are the sufferers in two-thirds of all
      TDIs observed. Although being a major fraction, crown-related fractures are a
      less severe form of TDIs with respect to their complications and sequelae.
      However, as with other types of traumatic injuries, the delay in seeking for
      immediate care following a traumatic injury and the lack of appropriate treatment
      may compromise long-term outcomes. This article reviews the occurrence,
      management, and prognosis of crown-related fractures in primary and permanent
      teeth in light of the recent literature. 

PMID- 24118991
TI  - Human tissue in systems medicine.
AB  - Histopathology, the examination of an architecturally artefactual, two
      dimensional and static image remains a potent tool allowing diagnosis and
      empirical expectation of prognosis. Considerable optimism exists that the advent
      of molecular genetic testing and other biomarker strategies will improve or even
      replace this ancient technology. A number of biomarkers already add considerable
      value for prediction of whether a treatment will work. In this short review we
      argue that a systems medicine approach to pathology will not seek to replace
      traditional pathology, but rather augment it. Systems approaches need to
      incorporate quantitative morphological, protein, mRNA and DNA data. A significant
      challenge for clinical implementation of systems pathology is how to optimize
      information available from tissue, which is frequently sub-optimal in quality and
      amount, and yet generate useful predictive models that work. The transition of
      histopathology to systems pathophysiology and the use of multiscale data sets
      usher in a new era in diagnosis, prognosis and prediction based on the analysis
      of human tissue. 

PMID- 24118992
TI  - MRI-safe robot for targeted transrectal prostate biopsy: animal experiments.
AB  - OBJECTIVES: To study the feasibility and safety of using a magnetic resonance
      imaging (MRI)-safe robot for assisting MRI-guided transrectal needle placement
      and biopsy in the prostate, using a canine model. To determine the accuracy and
      precision afforded by the use of the robot while targeting a desired location in
      the organ. MATERIALS AND METHODS: In a study approved by the Institutional Animal
      Care and Use Committee, six healthy adult male beagles with prostates of at least
      15 * 15 mm in size at the largest transverse section were chosen for the
      procedure. The probe portion of the robot was placed into the rectum of the dog,
      images were acquired and image-to-robot registration was performed. Images
      acquired after placement of the robot were reviewed and a radiologist selected
      targets for needle placement in the gland. Depending on the size of the prostate,
      up to a maximum of six needle placements were performed on each dog. After needle
      placement, robot-assisted core biopsies were performed on four dogs that had
      larger prostate volumes and extracted cores were analysed for potential
      diagnostic value. RESULTS: Robot-assisted MRI-guided needle placements were
      performed to target a total of 30 locations in six dogs, achieving a targeting
      accuracy of 2.58 mm (mean) and precision of 1.31 mm (SD). All needle placements
      were successfully completed on the first attempt. The mean time required to
      select a desired target location in the prostate, align the needle guide to that
      point, insert the needle and perform the biopsy was ~ 3 min. For this targeting
      accuracy study, the inserted needle was also imaged after its placement in the
      prostate, which took an additional 6-8 min. Signal-to-noise ratio analysis
      indicated that the presence of the robot within the scanner bore had minimal
      impact on the quality of the images acquired. Analysis of intact biopsy core
      samples indicated that the samples contained prostatic tissues, appropriate for
      making a potential diagnosis. Dogs used in the study did not experience device-
      or procedure-related complications. CONCLUSIONS: Results from this preclinical
      pilot animal study suggest that MRI-targeted transrectal biopsies are feasible to
      perform and this procedure may be safely assisted by an MRI-safe robotic device.

PMID- 24118993
TI  - Midazolam, as a co-induction agent, has propofol sparing effects but also
      decreases systolic blood pressure in healthy dogs.
AB  - OBJECTIVE: To evaluate the effects of the co-administration of midazolam on the
      dose requirement for propofol anesthesia induction, heart rate (HR), systolic
      arterial pressure (SAP) and the incidence of excitement. STUDY DESIGN:
      Prospective, randomized, controlled and blinded clinical study, with owner
      consent. ANIMALS: Seventeen healthy, client owned dogs weighing 28 +/- 18 kg and
      aged 4.9 +/- 3.9 years old. METHODS: Dogs were sedated with acepromazine 0.025 mg
      kg(-1) and morphine 0.25 mg kg(-1) intramuscularly (IM), 30 minutes prior to
      induction of anesthesia. Patients were randomly allocated to receive midazolam
      (MP; 0.2 mg kg(-1) ) or sterile normal saline (CP; 0.04 mL kg(-1) ) intravenously
      (IV) over 15 seconds. Propofol was administered IV immediately following test
      drug and delivered at 3 mg kg(-1)  minute(-1) until intubation was possible.
      Scoring of pre-induction sedation, ease of intubation, quality of induction, and
      presence or absence of excitement following co-induction agent, was recorded. HR,
      SAP and respiratory rate (fR ) were obtained immediately prior to, immediately
      following, and 5 minutes following induction of anesthesia. RESULTS: There were
      no significant differences between groups with regard to weight, age, gender, or
      sedation. Excitement occurred in 5/9 dogs following midazolam administration,
      with none noted in the control group. The dose of propofol administered to the
      midazolam group was significantly less than in the control group. Differences in
      HR were not significant between groups. SAP was significantly lower in the
      midazolam group compared with baseline values 5 minutes after its administration.
      However, values remained clinically acceptable. CONCLUSIONS AND CLINICAL
      RELEVANCE: The co-administration of midazolam with propofol decreased the total
      dose of propofol needed for induction of anesthesia in sedated healthy dogs,
      caused some excitement and a clinically unimportant decrease in SAP.

PMID- 24118994
TI  - Alternative transcription generates multiple Mitf isoforms with different
      expression patterns and activities in medaka.
AB  - Microphthalmia-associated transcription factor (Mitf) is best known for distinct
      functions in multiple cell lineages including melanocytes, mast cells, and
      osteoclasts. In mammals, mitf produces multiple Mitf isoforms by alternative
      transcription and splicing. The fish medaka has two mitf genes, mitf1 and mitf2.
      Here, we report differential expression and activities of medaka Mitf isoforms.
      Molecular cloning identified four mitf1 variants encoding isoforms Mitf1A, MitfB,
      MitfH, and MitfM, and only one mitf2RNA encoding Mitf2M, which exhibited
      differential expression. Mitf1 isoforms and Mitf2M differed dramatically in
      activating the dazl and tyrosinase promoters DAZ and TYR. Interestingly,
      Mitf1DeltaN, an N-terminus-less Mitf1 mutant form, retained activity to activate
      TYR but not DAZ. Importantly, Mitf1B was also sufficient for inducing melanocyte
      differentiation and endogenous tyrosinase RNA expression in medaka embryonic stem
      cells. Intriguingly, Mitf1 isoforms possessed considerable differences in
      inducing the expression of multiple cell lineage marker genes. Therefore,
      alternative mitf transcription is a conserved mechanism from fish to mammals, and
      medaka Mitf1 isoforms show differences in expression and activity. We conclude
      that differential expression of isoforms contributes to multiple distinct
      functions of Mitf in vertebrates. 

PMID- 24118995
TI  - Relationship of socioeconomic status with health behaviors and self-perceived
      health in the elderly: A community-based study, Turkey.
AB  - AIM: The purpose of the present study was to determine the effects of
      socioeconomic status on health behaviors and perceived health. METHODS: The
      present cross-sectional study included 2947 community-dwelling older adults aged
      65 years and older. Dependent variables were health behaviors and self-perceived
      health. The independent variable was socioeconomic status. RESULTS: In men, the
      risk of unhealthy diet was higher among the uneducated group (OR 4.48) and among
      those with poor/very poor economic status (OR 3.31). Additionally, in men, having
      poor/very poor self-perceived health was found to be 3.50-fold significantly
      higher among the uneducated group than the secondary school and higher-educated
      group. Lower education level and lower social class were found to be protective
      factors for smoking in women. In women, the risk of unhealthy diet was found to
      be 1.54- and 2.18-fold significantly higher, respectively, among those who
      graduated from primary school and uneducated. There was also a relationship
      between poor/very poor economic status and unhealthy diet among elderly women (OR
      2.80). In women, the risk of physical inactivity was found to be 1.98-fold
      significantly higher in the uneducated group and 1.79-fold significantly higher
      in those with poor/very poor economic status, 0.33-fold significantly lower in
      skilled employees/white collar workers. With regard to self-perceived health
      status, education level and perceived economic status were significantly related
      to poor/very poor health status in women (OR 2.09 and OR 4.08, respectively).
      CONCLUSION: In older men and women, lower socioeconomic status increases the risk
      of unhealthy diet and poor health perception. In older women, lower socioeconomic
      status is a protective factor for smoking, but it also increases physical
      inactivity.

PMID- 24118996
TI  - Experience of a specialist centre in the management of anastomotic sinus
      following leaks after low rectal or ileal pouch-anal anastomosis with diverting
      stoma.
AB  - AIM: The natural history and appropriate management of anastomotic sinus has not
      been clearly defined. The aim of this study was to evaluate the incidence,
      management and outcomes of anastomotic sinus. METHOD: The medical records of all
      patients who underwent a low anterior resection (LAR) or an ileal pouch-anal
      anastomosis (IPAA) with a diverting loop ileostomy (LI) and with contrast enema
      performed before planned stoma closure between 2001 and 2011 were retrospectively
      reviewed. The radiological features of the sinus tract, treatment and outcome of
      anastomotic sinus were studied. RESULTS: Twenty patients (8.2%) were found to
      have anastomotic sinuses out of the total of 244 patients who had undergone LAR
      (n = 146) or IPAA (n = 98) with LI. Of these, 13 (65%) had prior symptomatic
      leaks, while seven did not. Twelve patients (60%) were found to have simple sinus
      tracts, while eight had complex sinuses (associated with either pelvic cavities
      or severe strictures). Five patients with simple tracts were treated with
      observation alone. Fifteen patients underwent surgical interventions. Overall,
      with a median follow-up of 28 (6-73) months, 16 patients (80%) had resolution of
      their sinuses. All of 12 patients (100%) with simple sinus tracts and four of
      eight patients (50%) with complex sinuses underwent successful stoma reversals
      after 8 (3.5-24) months following the initial surgery (P = 0.01). CONCLUSION:
      Patients with simple tracts are significantly more likely to have complete
      resolution of sinuses than patients with complex sinuses. Persistent sinus
      associated with either a pelvic cavity or severe stricture despite surgical
      intervention is likely to lead to a permanent stoma.

PMID- 24118997
TI  - Do low levels of beta-endorphin in the cerebrospinal fluid indicate defective top
      down inhibition in patients with chronic neuropathic pain? A cross-sectional,
      comparative study.
AB  - OBJECTIVE: Pain medicine still lacks mechanism-specific biomarkers to guide
      diagnosis and treatment, and defective top-down modulation is an important factor
      in the pathophysiology of chronic pain conditions. Using modern analytical tools
      and advanced multivariate statistical analysis, the aim of this study was to
      revisit two classical potential biomarkers of pro- and anti-nociception in humans
      (substance P and beta-endorphin), focusing particularly on the cerebrospinal
      fluid (CSF). DESIGN: Cross-sectional, comparative, observational study. SUBJECTS:
      Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain
      refractory to conventional treatment (N = 15) and healthy controls (N = 19) were
      included. METHODS: Samples were taken from CSF and blood, and levels of substance
      P and beta-endorphin were investigated using a Luminex technology kit. RESULTS:
      We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66
      +/- 11 pcg/mL) compared with healthy controls (115 +/- 14 pcg/mL) (P = 0.017).
      Substance P levels in the CSF did not differ (20 +/- 2 pcg/mL, 26 +/- 2, P =
      0.08). However, our multivariate data analysis showed that belonging to the
      patient group was associated with low levels of both substances in the CSF. A
      higher correlation between the levels of beta-endorphin and substance P in CSF
      was found in healthy controls than in patients (rs  = 0.725, P < 0.001 vs. rs  =
      0.574, P = 0.032). CONCLUSIONS: Patients with chronic neuropathic pain due to
      trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that
      this could indicate a defective top-down modulation of pain in chronic
      neuropathic pain. Our results also illustrate the importance of taking a system
      wide, multivariate approach when searching for biomarkers.

PMID- 24118998
TI  - Inter-arm difference in systolic blood pressure-"the plot stiffens"-.

PMID- 24118999
TI  - Twin studies in inherited eye disease.
AB  - Eye diseases represent a significant source of health impairment in humans. Twin
      studies offer an excellent model to dissect the genetic basis of human diseases.
      In this review, we discuss the potential advantages of using twin-based studies
      in investigating the genetics of eye diseases--from heritability estimation to
      identifying underlying genetic and epigenetic changes. We also discuss some of
      the notable findings of twin studies exploring the genetics of eye diseases.
      Finally, we suggest other novel approaches that can be utilized to tap the
      potential of twin studies to provide a more complete understanding of genetic
      factors underlying ocular diseases.

PMID- 24119001
TI  - Elevation of serum cytokines preceding elevation of liver enzymes in a case of
      drug-induced liver injury.
AB  - A 50-year-old man who was being treated for both pneumonia and type 2 diabetes
      mellitus complained of abdominal distention on the 16th hospital day. Liver
      enzyme elevation without symptoms was detected on the 17th hospital day. Based on
      a Roussel Uclaf Causality Assessment Method score of 10 and a Japan Digestive
      Disease Week score of 9, we diagnosed the patient as having drug-induced liver
      injury (DILI). Simultaneous assays of the levels of cytokines revealed that the
      elevation of the levels of interleukin (IL)-1beta, IL-10, IL-12, IL-13 and tumor
      necrosis factor-alpha preceded the elevation of the serum liver enzymes. This
      case suggests that some cytokines or related molecules are potentially useful as
      early-phase biomarkers for DILI. 

PMID- 24119000
TI  - Meta-analysis on blood transcriptomic studies identifies consistently coexpressed
      protein-protein interaction modules as robust markers of human aging.
AB  - The bodily decline that occurs with advancing age strongly impacts on the
      prospects for future health and life expectancy. Despite the profound role of age
      in disease etiology, knowledge about the molecular mechanisms driving the process
      of aging in humans is limited. Here, we used an integrative network-based
      approach for combining multiple large-scale expression studies in blood (2539
      individuals) with protein-protein Interaction (PPI) data for the detection of
      consistently coexpressed PPI modules that may reflect key processes that change
      throughout the course of normative aging. Module detection followed by a meta
      analysis on chronological age identified fifteen consistently coexpressed PPI
      modules associated with chronological age, including a highly significant module
      (P = 3.5 * 10(-38)) enriched for 'T-cell activation' marking age-associated
      shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 * 10(-10)).
      Adjusting the analysis in the compendium for the 'T-cell activation' module
      showed five consistently coexpressed PPI modules that robustly associated with
      chronological age and included modules enriched for 'Translational elongation',
      'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535
      individuals, four of five modules consistently associated with chronological age,
      underpinning the robustness of the approach. We found three of five modules to be
      significantly enriched with aging-related genes, as defined by the GenAge
      database, and association with prospective survival at high ages for one of the
      modules including ASF1A. The hereby-detected age-associated and consistently
      coexpressed PPI modules therefore may provide a molecular basis for future
      research into mechanisms underlying human aging.

PMID- 24119002
TI  - Reduced intensity transplantation for congenital amegakaryocytic
      thrombocytopenia: report of a case and review of the literature.
AB  - CAMT is a bone marrow failure syndrome that usually presents with isolated
      thrombocytopenia soon after birth. HSCT is curative, and MAC is associated with
      increased transplant-related morbidity and mortality, especially in the unrelated
      setting. We used a RIC regimen with alemtuzumab, fludarabine, and melphalan in a
      seven-month-old patient with CAMT who underwent a MUD HSCT. The transplant was
      well tolerated with few complications. Neutrophil and platelet engraftment
      occurred on day +12 and +29, respectively, and she had 100% donor chimerisms on
      days +19.

PMID- 24119004
TI  - Changes in the body posture of women occurring with age.
AB  - BACKGROUND: A current topic in the field of geriatrics still needing a great deal
      of study is the changes in body posture occurring with age. Symptoms of these
      changes can be observed starting between the ages of 40-50 years with a slow
      progression that increases after 60 years of age. The aims of this study were to
      evaluate parameters characterizing the posture of women over the age of 60 years
      compared with a control group and to determine the dynamics of body posture
      changes in the following decades. METHODS: The study included 260 randomly
      selected women. The study group consisted of 130 women between the ages of 60-90
      years (Older Women). The control group (Younger Women) consisted of 130 women
      between the ages of 20-25 years (posture stabilization period). The
      photogrammetric method was used to evaluate body posture using the phenomenon of
      the projection chamber. The study was conducted according to generally accepted
      principles. RESULTS: In the analysis of parameters characterizing individual
      slope curves, results were varied among different age groups. The lumbar spine
      slope did not show significant differences between different age groups (p =
      0.6952), while statistically significant differences (p = 0.0000) were found in
      the thoracic-lumbar spine slope (p = 0.0033) and upper thoracic spine slope. Body
      angle was shown to increase with age (p = 0.0000). Thoracic kyphosis depth
      significantly deepened with age (p = 0.0002), however, the thoracic kyphosis
      angle decreased with age (p = 0.0000). An increase in asymmetries was noticed,
      provided by a significantly higher angle of the shoulder line (p = 0.0199) and
      the difference in height of the lower shoulder blade angle (p = 0.0007)
      measurements in the group of older women. CONCLUSIONS: Changes in the parameters
      describing body posture throughout consecutive decades were observed. Therapy for
      women over the age of 60 years should involve strengthening of the erector spinae
      muscles and controlling body posture with the aim of reducing trunk inclination
      and deepening of thoracic kyphosis. Moreover, exercises shaping lumbar lordosis
      should be performed to prevent its flattening.

PMID- 24119005
TI  - A behavioral comparison of the common laboratory rat strains Lister Hooded,
      Lewis, Fischer 344 and Wistar in an automated homecage system.
AB  - Behavioral characterization is an important part of establishing novel animal
      models, but classical behavioral tests struggle to reveal conclusive results due
      to problems with both reproducibility and validity. On the contrary, automated
      homecage observations are believed to produce robust outcomes that relate more to
      natural animal behavior. However, information on the behavior of background
      strains from such observations, which could provide important reference material,
      is rare. For this reason, we compared the behavior of the commonly used Lister
      Hooded, Lewis, Fischer 344 and Wistar rats during 70 h of exposure to an
      automated homecage system at 2, 4 and 6 months of age. We found considerable
      strain differences in metabolic parameters, novelty-induced and baseline activity
      related behavior as well as differences in the development of these parameters
      with age. The results are discussed in terms of advantages and disadvantages of
      the system compared to classical behavioral tests, as well as the system's
      ability to recreate common findings in literature. 

PMID- 24119003
TI  - Integrated RNA-seq and sRNA-seq analysis identifies novel nitrate-responsive
      genes in Arabidopsis thaliana roots.
AB  - BACKGROUND: Nitrate and other nitrogen metabolites can act as signals that
      regulate global gene expression in plants. Adaptive changes in plant morphology
      and physiology triggered by changes in nitrate availability are partly explained
      by these changes in gene expression. Despite several genome-wide efforts to
      identify nitrate-regulated genes, no comprehensive study of the Arabidopsis root
      transcriptome under contrasting nitrate conditions has been carried out. RESULTS:
      In this work, we employed the Illumina high throughput sequencing technology to
      perform an integrated analysis of the poly-A + enriched and the small RNA
      fractions of the Arabidopsis thaliana root transcriptome in response to nitrate
      treatments. Our sequencing strategy identified new nitrate-regulated genes
      including 40 genes not represented in the ATH1 Affymetrix GeneChip, a novel
      nitrate-responsive antisense transcript and a new nitrate responsive miRNA/TARGET
      module consisting of a novel microRNA, miR5640 and its target, AtPPC3.
      CONCLUSIONS: Sequencing of small RNAs and mRNAs uncovered new genes, and enabled
      us to develop new hypotheses for nitrate regulation and coordination of carbon
      and nitrogen metabolism.

PMID- 24119006
TI  - Brevibacillus themoruber: a promising microbial cell factory for
      exopolysaccharide production.
AB  - AIMS: This study aims to identify a high level exopolysaccharide (EPS) producer
      thermophile that in turn could be used as a model organism to study the
      biological mechanisms and whole genome organization of EPS-producing thermophilic
      bacteria. METHODS AND RESULTS: Thermophilic isolates were screened, and then
      growth and EPS production of the best producer Brevibacillus thermoruber strain
      423 were investigated under different carbon and nitrogen sources, temperature,
      pH and agitation rates. Rheological characterization revealed that the EPS
      behaved like a typical Newtonian fluid and viscosity of the EPS solution
      increased with increasing Ca(2+) ion concentration. Chemical characterization by
      TLC, GC-MS, FT-IR and NMR suggested a heteropolymer structure with glucose as
      major monomer unit. High biocompatibility of pure EPS fractions suggested their
      potential use in biomedical applications. CONCLUSIONS: This study reports on the
      comprehensive description of microbial production conditions as well as chemical,
      rheological and biological characterization of the EPS produced by B. thermoruber
      strain 423. The bioreactor cultures were found to reach two times higher yields
      and three times higher productivities when compared with literature. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Brevibacillus thermoruber strain 423 combined the
      advantages of its nonpathogenicity with the advantages of fast productivity and
      hence proved to be a very promising model organism and cell factory for microbial
      EPS production.

PMID- 24119007
TI  - A case of selective immunoglobulin A deficiency with anti-neutrophil cytoplasmic
      antibody-associated glomerulonephritis.

PMID- 24119008
TI  - A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in
      childhood is related to metabolic control, macroalbuminuria, and retinopathy in
      early adulthood--a pilot study using two nation-wide population based quality
      registries.
AB  - BACKGROUND: Intensive treatment of patients with type 1 diabetes delays the onset
      of long-term complications. OBJECTIVES: On the basis of the information from two
      nation-wide quality registers, we investigated to which extent HbA1c values 3-15
      months after diagnosis in childhood are related to metabolic control,
      albuminuria, and retinopathy in early adulthood. METHODS: In Sweden, physicians
      register all children and adolescents with type 1 diabetes mellitus in the
      Swedish Pediatric Quality Registry. After 18 yr of age, people with diabetes are
      followed by the Swedish National Diabetes Register. We identified 1543 children
      and adolescents with a mean age of 13.9 yr at diagnosis and a mean duration of
      type 1 diabetes mellitus of 7.1 yr. RESULTS: Children and adolescents with poor
      metabolic control (mean HbA1c >= 70 mmol/mol (8.6 %)) adjacent to diagnosis had a
      significantly higher mean HbA1c value years later as adults than did patients
      with a good metabolic control [<50 mmol/mol (6.7%) (p < 0.001)]. The patients in
      the high group were also less physically active and smoked more as adults. The
      proportion of females was higher in the poor metabolic group. Patients with a
      high mean HbA1c 3-15 months after diagnosis had significantly more often
      macroalbuminuria and retinopathy in early adulthood. CONCLUSIONS: Metabolic
      control adjacent to the diagnosis of type 1 diabetes in childhood or adolescence
      can predict metabolic control in early adulthood. It is therefore very important
      that pediatric diabetes teams identify key factors for successful early metabolic
      control. Actively using quality registries may be one such factor.

PMID- 24119009
TI  - Exploring the northern limit of the distribution of Saccharomyces cerevisiae and
      Saccharomyces paradoxus in North America.
AB  - We examined the northern limit of Saccharomyces cerevisiae and Saccharomyces
      paradoxus in northeast America. We collected 876 natural samples at 29 sites and
      applied enrichment methods for the isolation of mesophilic yeasts. We uncovered a
      large diversity of yeasts, in some cases, associated with specific substrates.
      Sequencing of the ITS1, 5.8S and ITS2 loci allowed to assign 226 yeast strains at
      the species level, including 41 S. paradoxus strains. Our intensive sampling
      suggests that if present, S. cerevisiae is rare at these northern latitudes. Our
      sampling efforts spread across several months of the year revealed that
      successful sampling increases throughout the summer and diminishes significantly
      at the beginning of the fall. The data obtained on the ecological context of
      yeasts corroborate what was previously reported on Pichiaceae,
      Saccharomycodaceae, Debaryomycetaceae and Phaffomycetaceae yeast families. We
      identified 24 yeast isolates that could not be assigned to any known species and
      that may be of taxonomic, medical, or biotechnological importance. Our study
      reports new data on the taxonomic diversity of yeasts and new resources for
      studying the evolution and ecology of S. paradoxus. 

PMID- 24119010
TI  - Coadministration of anastrozole sustains therapeutic testosterone levels in
      hypogonadal men undergoing testosterone pellet insertion.
AB  - INTRODUCTION: Current U.S. Food and Drug Administration-approved therapies for
      hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP)
      require a minor office procedure every 3 to 4 months. The need for repeated
      insertions increases the likelihood of a complication. Anastrozole (AZ) is an
      aromatase inhibitor that has been used off-label for the treatment of male
      hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and
      increasing gonadotropin (GTP) levels. AIM: We hypothesized that the concomitant
      use of AZ with TP insertions would sustain therapeutic T levels and increase the
      interval between TP insertions. METHODS: Men treated with TP for hypogonadism at
      an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a
      way of potentially decreasing the frequency of TP insertions. Total T (TT), free
      T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle
      stimulating hormone FSH levels were obtained prior to T replacement and at 6 and
      15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels
      were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed
      our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics,
      TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a
      Tukey's test. MAIN OUTCOME MEASURE: TT level at 6, 15, or >15 weeks from TP
      insertion. RESULTS: Thirty-eight men with 65 insertions were analyzed. The TP AZ
      group had significantly higher TT and FT levels than the TP group at >120 days (P
      < 0.05). The TP group had significantly higher E2 levels at all time points (P <
      0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion
      in TP AZ was 198 days vs. 128 days in the TP group. CONCLUSION: Men on TP AZ
      maintain therapeutic T levels longer than men on TP alone and have significantly
      less GTP suppression.

PMID- 24119011
TI  - Monomerization of C-reactive protein requires glycoprotein IIb-IIIa activation:
      pentraxins and platelet deposition.
AB  - BACKGROUND: Pentraxins are inflammatory mediators linked to cardiovascular
      disease; however, their role in thrombosis remains to be fully elucidated. AIMS:
      We investigated the role of pentraxins in thrombus formation on different
      vascular substrates under flow conditions. METHODS: Native C-reactive protein
      (nCRP) and serum amyloid P (SAP) effects on thrombosis were evaluated under flow
      conditions on substrates placed in flat perfusion chambers. nCRP and dissociated
      monomeric CRP (mCRP) distributions were visualized by use of confocal microscopy.
      The effects of nCRP on vascular substrates were tested in the Badimon chamber.
      RESULTS: mCRP, but not nCRP, induced a significant activation in platelet
      deposition, whereas SAP induced an activation only on fibrinogen-coated
      substrates. The effects of CRP on platelet deposition were significantly reduced
      by statin treatment. mCRP resulting from recirculation of blood containing nCRP
      over a thrombogenic vessel wall induced increased platelet deposition. Blocking
      glycoprotein IIb-IIIa prevented the effects of CRP dissociation and significantly
      reduced platelet deposition. Annexin V treatment did not block monomerization of
      CRP on activated platelets. CONCLUSIONS: Under flow conditions, platelet
      deposited on all tested biological substrates support nCRP dissociation into
      mCRP. The effect is dependent on the thrombogenic potency of the substrate to
      trigger initial platelet deposition. Exposure of glycoprotein IIb-IIIa in the
      platelet surface supports nCRP dissociation. CRP monomerization was not dependent
      on the aminophospholipid exposed on the surface of activated platelets. The
      dissociated mCRP is trapped in the growing platelet aggregate and stimulates
      further platelet deposition. SAP increases platelet deposition only on fibrin
      monolayers. Therefore, pentraxins induce a platelet activation effect linking
      inflammation and thrombosis.

PMID- 24119012
TI  - The design and conduct of a community-based registry and biorepository: a focus
      on cardiometabolic health in Latinos.
AB  - BACKGROUND: Latinos are disproportionately impacted by obesity and type 2
      diabetes but remain underrepresented in biomedical research. Therefore, the
      purpose of this project was to develop a research registry and biorepository to
      examine cardiometabolic disease risk in the Latino community of Phoenix, Arizona.
      The overarching goal was to establish the research infrastructure that would
      encourage transdisciplinary research regarding the biocultural mechanisms of
      obesity-related health disparities and facilitate access to this research for the
      Latino community. METHODS: Prior to recruitment, key stakeholders from the local
      Latino community were engaged to develop a broad rapport within the community and
      seek advice regarding recruitment, enrollment, and follow-up. Self-identified
      community-dwelling Latinos underwent a comprehensive cardiometabolic health
      assessment that included anthropometrics, a fasting laboratory panel, and a 2
      hour oral glucose tolerance test with measures of insulin and glucose to estimate
      insulin action and secretion. Separate consent was requested for future contact
      and banking of serum, DNA, and RNA. Research collaborations were sought out based
      on the cultural and metabolic profile of participants, faculty research agendas,
      and the potential for generating hypotheses. RESULTS: A total of 667 participants
      (20.4% children, and 79.6% adults) were enrolled with 97% consenting to the
      registry and 94% to banking of samples. The prevalence of overweight/obesity was
      50% in children and 81% in adults. Nearly 20% of children and more than 45% of
      the adults exhibited some degree of hyperglycemia. To date, more than 15 research
      projects have been supported through this infrastructure and have included
      projects on the molecular biology of insulin resistance to the sociocultural
      determinants of health behaviors and outcomes. CONCLUSIONS: The high prevalence
      of obesity and cardiometabolic disease risk factors coupled with the overwhelming
      majority of participants consenting to be re-contacted, highlights the importance
      of supporting research infrastructure to generate hypotheses about obesity
      related health in Latinos. Future studies that stem from the initial project will
      likely advance the limited understanding regarding the biocultural determinants
      of health disparities in the Latino community.

PMID- 24119013
TI  - Evaluation and outcomes of patients admitted to a tertiary medical assessment
      unit with acute chest pain of possible coronary origin.
AB  - OBJECTIVES: The study aims to (i) profile clinical characteristics, risk
      estimates of acute coronary syndrome (ACS), use and yield of non-invasive cardiac
      testing, discharge diagnosis and 30-day outcomes among patients admitted with
      acute chest pain of possible coronary origin; and (ii) construct a risk
      stratification algorithm that informs management decisions. METHODS: This is a
      retrospective cohort study of 130 consecutive patients admitted to a tertiary
      hospital medical assessment unit between 24 January and 22 March 2012. Estimates
      of ACS risk were based on Australian guidelines and Thrombolysis in Myocardial
      Infarction (TIMI) scores. RESULTS: Patients were of mean age 61 years, 45% had
      known coronary artery disease (CAD), 58% presented with typical ischaemic pain,
      82% had intermediate to high ACS risk and 61% underwent testing. Myocardial
      ischaemia was cardiologist-confirmed discharge diagnosis in 29% of patients, and
      was associated with known CAD, typical pain, multiple risk factors and high TIMI
      risk scores (P < 0.001 for all associations). Of 98 non-invasive investigations,
      9% (95% CI, 5-17%) were positive for myocardial ischaemia. Major adverse event
      rate at 30 days was 0.8% (95% CI, <0.1-6%). An algorithm was constructed that
      integrates known CAD, ACS risk and TIMI scores in identifying low-risk patients
      capable of rapid discharge from EDs without further investigation, and
      classifying the remainder into risk groups that informs choice of investigations
      and need for telemetry. CONCLUSIONS: In patients with indeterminate chest pain,
      clinical features and risk scores identify most with myocardial ischaemia. An
      algorithm is presented that might inform triaging, early discharge, choice of
      testing and need for telemetry.

PMID- 24119014
TI  - Clinical and virological features of occult hepatitis B in patients with HBsAg
      seroclearance post-treatment or spontaneously.
AB  - BACKGROUND: Occult hepatitis B virus (HBV) infection (OHB) may exist in patients
      experiencing hepatitis B surface antigen (HBsAg) seroclearance. AIMS: We examined
      the clinical and virological features of OHB in patients who lost HBsAg post
      treatment or spontaneously. METHODS: We collected 44 patients with HBsAg
      seroclearance: 15 patients with dual HBV/hepatitis C virus (HCV) infection who
      lost HBsAg after peginterferon alfa-2a (PEG-IFN) plus ribavirin therapy; 13 HBV
      mono-infected patients who lost HBsAg after various oral antiviral therapies; and
      16 patients who lost HBsAg spontaneously. OHB was defined as detectable serum HBV
      DNA in the absence of HBsAg. Viral mutations associated with OHB were identified
      by comparison with matched controls that remained positive for HBsAg, and further
      characterized in vitro. RESULTS: The prevalence of OHB was 34.1% (15/44) in all
      patients, which was not significantly different among three groups. One mutation
      in surface promoter/polymerase region, C3050T (preS1T68I), was identified to be
      associated with the seroclearance of HBsAg in six cases. This mutation does not
      change the amino acid sequence of the polymerase protein. The S promoter activity
      was significantly lower in the construct containing C3050T mutation as compared
      with the wild-type (P = 0.0008). However, this mutation did not affect HBV
      replication, transcription and translation in the context of the full-length HBV
      genome. OHB was not rare in patients with HBsAg seroclearance. CONCLUSIONS: One
      mutation, C3050T (preS1T68I), decreased S promoter activity; nevertheless, other
      factors may play more important role in the clearance of HBsAg in these OHB
      patients.

PMID- 24119015
TI  - Inactivation of a Pleurotus ostreatus versatile peroxidase-encoding gene (mnp2)
      results in reduced lignin degradation.
AB  - Lignin biodegradation by white-rot fungi is pivotal to the earth's carbon cycle.
      Manganese peroxidases (MnPs), the most common extracellular ligninolytic
      peroxidases produced by white-rot fungi, are considered key in ligninolysis.
      Pleurotus ostreatus, the oyster mushroom, is a preferential lignin degrader
      occupying niches rich in lignocellulose such as decaying trees. Here, we provide
      direct, genetically based proof for the functional significance of MnP to P.
      ostreatus ligninolytic capacity under conditions mimicking its natural habitat.
      When grown on a natural lignocellulosic substrate of cotton stalks under solid
      state culture conditions, gene and isoenzyme expression profiles of its short MnP
      and versatile peroxidase (VP)-encoding gene family revealed that mnp2 was
      predominately expressed. mnp2, encoding the versatile short MnP isoenzyme 2 was
      disrupted. Inactivation of mnp2 resulted in three interrelated phenotypes,
      relative to the wild-type strain: (i) reduction of 14% and 36% in lignin
      mineralization of stalks non-amended and amended with Mn(2+), respectively; (ii)
      marked reduction of the bioconverted lignocellulose sensitivity to subsequent
      bacterial hydrolyses; and (iii) decrease in fungal respiration rate. These
      results may serve as the basis to clarify the roles of the various types of
      fungal MnPs and VPs in their contribution to white-rot decay of wood and
      lignocellulose in various ecosystems.

PMID- 24119016
TI  - Minimum end-tidal sevoflurane concentration necessary to prevent movement during
      a constant rate infusion of morphine, or morphine plus dexmedetomidine in ponies.
AB  - OBJECTIVE: To compare the effects of a constant rate infusion (CRI) of
      dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal
      sevoflurane concentration necessary to prevent movement (MACNM ) in ponies. STUDY
      DESIGN: Prospective, randomized, crossover, 'blinded', experimental study.
      ANIMALS: Five healthy adult gelding ponies were anaesthetized twice with a 3-week
      washout period. METHODS: After induction of anaesthesia with sevoflurane in
      oxygen (via nasotracheal tube), the ponies were positioned on a surgical table
      (T0), and anaesthesia was maintained with sevoflurane (Fe'SEVO 2.5%) in 55%
      oxygen. Monitoring included pulse oximetry, electrocardiography and measurement
      of anaesthetic gases, arterial blood pressure and body temperature. The ponies
      were mechanically ventilated and randomly allocated to receive IV treatment M
      [morphine 0.15 mg kg-1 (T10-T15) followed by a CRI (0.1 mg kg-1 hour-1)] or
      treatment DM [dexmedetomidine 3.5 MUg kg-1 plus morphine 0.15 mg kg-1 (T10-T15)
      followed by a CRI of dexmedetomidine 1.75 MUg kg-1 hour-1 and morphine 0.1 mg kg
      1 hour-1]. At T60, a stepwise MACNM determination was initiated using constant
      current electrical stimuli at the skin of the lateral pastern region. Triplicate
      MACNM estimations were obtained and then averaged in each pony. Wilcoxon signed
      rank test was used to detect differences in MAC between treatments (alpha =
      0.05). RESULTS: Sevoflurane-morphine MACNM values (median (range) and mean +/-
      SD) were 2.56 (2.01-4.07) and 2.79 +/- 0.73%. The addition of a continuous
      infusion of dexmedetomidine significantly reduced sevoflurane MACNM values to
      0.89 (0.62-1.05) and 0.89 +/- 0.22% (mean MACNM reduction 67 +/- 11%). CONCLUSION
      AND CLINICAL RELEVANCE: Co-administration of dexmedetomidine and morphine CRIs
      significantly reduced the MACNM of sevoflurane compared with a CRI of morphine
      alone at the reported doses.

PMID- 24119017
TI  - Pathways to (specialized) care: patient costs and contacts en route to a first
      episode psychosis clinic.
AB  - AIM: To estimate the public health costs of specific help-seeking pathways into
      an early intervention psychosis clinic. METHODS: The sequence of police,
      emergency and mental health contacts utilized by 50 patients up to 1 year prior
      to admission was characterized using chart reviews and structured interviews.
      Cost estimates for contacts were obtained from provincial health/public service
      cost reports. RESULTS: A high-cost inpatient pathway and a low-cost outpatient
      pathway were identified, with the former exceeding the latter by a factor of 18.5
      in cost. This discrepancy was attributable to both the high cost of inpatient
      services and the long duration of inpatient admissions, as well as more frequent
      inpatient use of high-cost urgent services (e.g. police, emergency services).
      CONCLUSION: Given the substantial cost differential between inpatient and
      outpatient routes, additional clarification of modifiable factors that determine
      pathways to care could have significant implications to health service delivery
      costs for this population.

PMID- 24119018
TI  - The lethal and enduring inequity of deceased donor liver allocation policy for
      hepatocellular carcinoma in the United States.

PMID- 24119019
TI  - Hepatic oxidative stress in ovariectomized transgenic mice expressing the
      hepatitis C virus polyprotein is augmented through suppression of adenosine
      monophosphate-activated protein kinase/proliferator-activated receptor gamma co
      activator 1 alpha signaling.
AB  - AIM: Oxidative stress plays an important role in hepatocarcinogenesis of
      hepatitis C virus (HCV)-related chronic liver diseases. Despite the evidence of
      an increased proportion of females among elderly patients with HCV-related
      hepatocellular carcinoma (HCC), it remains unknown whether HCV augments hepatic
      oxidative stress in postmenopausal women. The aim of this study was to determine
      whether oxidative stress was augmented in ovariectomized (OVX) transgenic mice
      expressing the HCV polyprotein and to investigate its underlying mechanisms.
      METHODS: OVX and sham-operated female transgenic mice expressing the HCV
      polyprotein and non-transgenic littermates were assessed for the production of
      reactive oxygen species (ROS), expression of inflammatory cytokines and
      antioxidant potential in the liver. RESULTS: Compared with OVX non-transgenic
      mice, OVX transgenic mice showed marked hepatic steatosis and ROS production
      without increased induction of inflammatory cytokines, but there was no increase
      in ROS-detoxifying enzymes such as superoxide dismutase 2 and glutathione
      peroxidase 1. In accordance with these results, OVX transgenic mice showed less
      activation of peroxisome proliferator-activated receptor-gamma co-activator
      1alpha (PGC-1alpha), which is required for the induction of ROS-detoxifying
      enzymes, and no activation of adenosine monophosphate-activated protein kinase
      alpha (AMPKalpha), which regulates the activity of PGC-1alpha. CONCLUSION: Our
      study demonstrated that hepatic oxidative stress was augmented in OVX transgenic
      mice expressing the HCV polyprotein by attenuation of antioxidant potential
      through inhibition of AMPK/PGC-1alpha signaling. These results may account in
      part for the mechanisms by which HCV-infected women are at high risk for HCC
      development when some period has passed after menopause.

PMID- 24119020
TI  - Novel simplified yeast-based assays of regulators of p53-MDMX interaction and p53
      transcriptional activity.
AB  - Yeast has proven to be an efficient model system for functional and
      pharmacological studies of the p53 tumour suppressor protein. In this work, the
      human p53-MDMX regulatory pathway was reconstituted in yeast. Additionally, by
      using the known inhibitor of p53-MDMX interaction, SJ-172550, the efficacy of a
      simplified yeast-based screening assay to search for inhibitors of p53-MDMX
      interaction is demonstrated for the first time. Moreover, further insights on p53
      transcriptional activity in yeast are provided. In particular, it is shown that
      the reported wild-type (wt) p53-induced yeast growth inhibition and cell cycle
      arrest is associated with actin depolarization and with an increase of actin mRNA
      and protein expression levels. The increase of actin protein levels was not
      observed with the p53 R273H mutant (a loss of function p53 mutation hotspot) and
      was further intensified with the toxic p53 V122A mutant (reported to exhibit
      higher transcriptional activity than wt p53 for selected p53 target sequences).
      Moreover, it is shown that the wt p53-induced actin protein levels are modulated
      by natural (MDM2 and MDMX) and chemical (pifithrin-alpha, nutlin-3a and SJ
      172550) regulators of p53 activity. Furthermore, wt p53 could stimulate
      transcription from a minimal promoter containing a fragment of the ACT1 upstream
      sequence. Thus, ACT1 is proposed as a putative endogenous p53 target gene. This
      finding may open the way for the development of simpler yeast p53 transactivation
      assays, not based on artificial reporter constructs, for the analysis of the
      impact of mutants, cofactors and small molecules on p53 transcriptional activity.

PMID- 24119021
TI  - Non-surgical interventions for the management of type 2 dens fractures: a
      systematic review.
AB  - BACKGROUND: Non-surgical immobilization strategies for type 2 odontoid fractures
      vary considerably, with some surgeons preferring rigid collars, halothoracic
      bracing or the Minerva brace. Choice of device should be informed by the
      effectiveness in achieving union, whilst minimizing mortality and complications.
      OBJECTIVES: Perform a systematic review evaluating the efficacy of non-surgical
      interventions for type 2 odontoid fractures. DATA SOURCES: MEDLINE (OvidSP),
      EMBASE (OvidSP) and The Cochrane Library, ClinicalTrials.gov, Current Controlled
      Trials. METHODS: We conducted a systematic review of studies directly comparing
      the halothoracic brace and cervical collars or the Minerva brace for union,
      mortality and complications. Studies were appraised for quality and bias, and
      results were pooled for analysis. RESULTS: Our search identified 1794 citations,
      13 of which met inclusion criteria. There were no randomized or prospective
      studies. All studies were small, retrospective and observational. Our results
      demonstrate a greater likelihood of developing stable union (osseous and
      fibrous); relative risk (RR) 1.27 (95% confidence intervals (CI) 1.03 to 1.57; P
      = 0.03); and airway complications; RR 7.52 (95% CI 1.39 to 40.83; P = 0.02) with
      halothoracic bracing compared with cervical collar. In patients >65, there was a
      greater risk of airway complications; RR 7.50 (0.96-58.36; P = 0.05). No other
      significant differences were identified. CONCLUSION: Evidence to support
      selection of non-surgical immobilization in type 2 odontoid fractures is poor.
      Osseous union has traditionally been the benchmark for 'successful' treatment;
      however, evidence of association between union and improved outcomes is lacking.
      We highlight the need for a randomized study to promote evidence-based decision
      making in the non-surgical management of this injury.

PMID- 24119022
TI  - Next-Gen phylogeography of rainforest trees: exploring landscape-level cpDNA
      variation from whole-genome sequencing.
AB  - Standardized phylogeographic studies across codistributed taxa can identify
      important refugia and biogeographic barriers, and potentially uncover how changes
      in adaptive constraints through space and time impact on the distribution of
      genetic diversity. The combination of next-generation sequencing and
      methodologies that enable uncomplicated analysis of the full chloroplast genome
      may provide an invaluable resource for such studies. Here, we assess the
      potential of a shotgun-based method across twelve nonmodel rainforest trees
      sampled from two evolutionary distinct regions. Whole genomic shotgun sequencing
      libraries consisting of pooled individuals were used to assemble species-specific
      chloroplast references (in silicio). For each species, the pooled libraries
      allowed for the detection of variation within and between data sets (each
      representing a geographic region). The potential use of nuclear rDNA as an
      additional marker from the NGS libraries was investigated by mapping reads
      against available references. We successfully obtained phylogeographically
      informative sequence data from a range of previously unstudied rainforest trees.
      Greater levels of diversity were found in northern refugial rainforests than in
      southern expansion areas. The genetic signatures of varying evolutionary
      histories were detected, and interesting associative patterns between functional
      characteristics and genetic diversity were identified. This approach can suit a
      wide range of landscape-level studies. As the key laboratory-based steps do not
      require prior species-specific knowledge and can be easily outsourced, the
      techniques described here are even suitable for researchers without access to wet
      laboratory facilities, making evolutionary ecology questions increasingly
      accessible to the research community. 

PMID- 24119023
TI  - Glutathione-enriched baker's yeast: production, bioaccessibility and intestinal
      transport assays.
AB  - AIMS: A glutathione (GSH) yeast-based biomass (Saccharomyces cerevisiae) was used
      to investigate GSH stability, solubilization during gastrointestinal digestion
      and GSH intestinal transport. METHODS AND RESULTS: A postgrowing procedure was
      applied to improve intracellular GSH yeast content. The presence of adenine (ADE)
      in the biotransformation solution (CYS-GLY-GLU mixture) and alternatively, a
      glucose shot after 4-h incubation, allowed to obtain cells containing about GSH
      1.6-1.7% dcw (dry cell weight) (control 0.5%). Yeast samples were subjected to in
      vitro gastrointestinal digestion and absorption assays employing Caco-2 and HT29
      MTX cell lines in different proportions (100/0, 70/30 and 50/50). Trials were
      also performed to verify intestinal cell viability. CONCLUSIONS: At least 87% of
      ingested GSH is available in reduced form for intestinal absorption. In vitro GSH
      transport assays indicated that GSH is poorly absorbed (<20%). Nevertheless,
      studies in response to oxidative stress induced by H2 O2 demonstrated a
      protective role of the GSH-enriched biomass towards intestinal cell viability.
      SIGNIFICANCE AND IMPACT OF STUDY: An enriched GSH yeast-based biomass has been
      obtained using a postgrowing procedure. Although GSH present in enriched yeasts
      is poorly absorbed by intestinal cells, this biomass showed an intestinal local
      protective effect, improving cells viability when a simulated oxidative stress
      was applied.

PMID- 24119024
TI  - High blood pressure in overweight and obese youth: implications for screening.
AB  - In the absence of evidence-based guidelines for high blood pressure screening in
      asymptomatic youth, a reasonable strategy is to screen those who are at high
      risk. The present study aimed to identify optimal body mass index (BMI)
      thresholds as a marker for high-risk youth to predict hypertension prevalence. In
      a cross-sectional study, youth aged 6 to 17 years (n=237,248) enrolled in an
      integrated prepaid health plan in 2007 to 2009 were classified according to their
      BMI and hypertension status. In moderately and extremely obese youth, the
      prevalence of hypertension was 3.8% and 9.2%, respectively, compared with 0.9% in
      normal weight youth. The adjusted prevalence ratios (95% confidence intervals) of
      hypertension for normal weight, overweight, moderate obesity, and extreme obesity
      were 1.00 (Reference), 2.27 (2.08-2.47), 4.43 (4.10-4.79), and 10.76 (9.99
      11.59), respectively. The prevalence of hypertension was best predicted by a BMI
      for-age >=94th percentile. These results suggest that all obese youth should be
      screened for hypertension. 

PMID- 24119025
TI  - Successful treatment of persisting neck pain after radical neck dissection using
      prism glasses.

PMID- 24119026
TI  - Beyond enhanced recovery.

PMID- 24119027
TI  - Illness cognition as a predictor of exercise habits and participation in cardiac
      prevention and rehabilitation programs after acute coronary syndrome.
AB  - BACKGROUND: Despite well-established medical recommendations, many cardiac
      patients do not exercise regularly either independently or through formal cardiac
      prevention and rehabilitation programs (CPRP). This non-adherence is even more
      pronounced among minority ethnic groups. Illness cognition (IC), i.e. the way
      people perceive the situation they encounter, has been recognized as a crucial
      determinant of health-promoting behavior. Few studies have applied a cognitive
      perspective to explain the disparity in exercising and CPRP attendance between
      cardiac patients from different ethnic backgrounds. Based on the Health Belief
      Model (HBM) and the Common Sense Model (CSM), the objective was to assess the
      association of IC with exercising and with participation in CPRP among
      Jewish/majority and Arab/minority patients hospitalized with acute coronary
      syndrome. METHODS: Patients (N = 420) were interviewed during hospitalization
      (January-2009 until August- 2010) about IC, with 6-month follow-up interviews
      about exercise habits and participation in CPRP. Determinants that predict active
      lifestyle and participation in CPRP were assessed using backward stepwise
      logistic regression. RESULTS: Perceived susceptibility to heart disease and sense
      and personal control were independently associated with exercising 6 months after
      the acute event (OR = 0.58, 95% CI: 0.42-0.80 and OR = 1.09, 95% CI: 1.02-1.17,
      per unit on a 5-point scale). Perceived benefits of regular exercise and a sense
      of personal control were independently associated with participation in CPRP (OR
      = 1.56, 95% CI: 1.12-2.16 and OR = 1.08, 95% CI: 1.01-1.15, per unit on a 5-point
      scale). None of the IC variables assessed could explain the large differences in
      health promoting behaviors between the majority and minority ethnic groups.
      CONCLUSIONS: IC should be taken into account in future interventions to promote
      physical activity and participation in CPRP for both ethnic groups. Yet, because
      IC failed to explain the gap between Arab and Jewish patients in those behaviors,
      other explanatory pathways such as psychological state or cultural views should
      be considered as potential areas for further research.

PMID- 24119030
TI  - International Journal of Dental Hygiene. Editorial.

PMID- 24119031
TI  - Improving oral health.

PMID- 24119029
TI  - Endoplasmic reticulum stress activates telomerase.
AB  - Telomerase contributes to cell proliferation and survival through both telomere
      dependent and telomere-independent mechanisms. In this report, we discovered that
      endoplasmic reticulum (ER) stress transiently activates the catalytic components
      of telomerase (TERT) expression in human cancer cell lines and murine primary
      neural cells. Importantly, we show that depletion of hTERT sensitizes cells to
      undergo apoptosis under ER stress, whereas increased hTERT expression reduces ER
      stress-induced cell death independent of catalytically active enzyme or DNA
      damage signaling. Our findings establish a functional link between ER stress and
      telomerase, both of which have important implications in the pathologies
      associated with aging and cancer. 

PMID- 24119033
TI  - Disseminated Rhizopus microsporus infection following allogeneic hematopoietic
      stem cell transplantation in a child with severe aplastic anemia.
AB  - Disseminated Rhizopus microsporus infections are uncommon in children and are
      resistant to echinocandin and azole antifungal agents. We describe a child with
      severe aplastic anemia who developed disseminated R. microsporus infection
      following allogeneic hematopoietic stem cell transplantation. R. microsporus was
      identified microscopically in the hepatic drain culture and was confirmed on the
      basis of 18S rRNA and 28S rRNA sequence analyses. The patient was treated
      successfully with hepatic drainage and amphotericin B deoxycholate.

PMID- 24119034
TI  - Clear corneal vitrectomy combined with phacoemulsification and foldable
      intraocular lens implantation.
AB  - BACKGROUND: We have developed a technique for the treatment of cataract and
      epiretinal membrane using a 25-gauge vitrectomy system through corneal ports.
      DESIGN: Randomized, prospective study, Toyama Prefectural Central Hospital,
      Toyama, Japan. PARTICIPANTS: Twenty eyes of equal patients scheduled for cataract
      surgery combined with vitrectomy. METHODS: Twenty eyes with cataract and
      epiretinal membrane were received treatment with our newly developed system
      (clear corneal vitrectomy) or the standard 25-gauge pars plana vitrectomy with
      corneal incision cataract surgery. The newly developed system uses 0.5-mm wide
      corneal side ports located at the superonasal, superotemporal and inferotemporal
      positions. After phacoemulsification using corneal incision, an infusion cannula
      was inserted from the inferotemporal port. Then core 25-gauge vitrectomy was
      performed using the corneal three port. After the epiretinal membrane was removed
      using forceps, an intraocular lens was implanted into the capsular bag. Finally,
      all corneal incision wounds were hydrated. MAIN OUTCOME MEASUREMENT: Visual
      acuity, intraocular pressure, corneal thickness, corneal endothelial cell and
      ocular inflammation were examined. RESULTS: All procedures were uncomplicated in
      both groups. There was no leakage of aqueous humour from the corneal wounds in
      the developed system. There were no significant differences in visual acuity,
      corneal thickness and endothelial cell density loss. CONCLUSIONS: Clear corneal
      vitrectomy would be a good option for selected cases with cataract and
      vitreoretinal diseases.

PMID- 24119035
TI  - Psychotherapy improved the sleep quality in a patient who was a victim of child
      sexual abuse: a case report.
AB  - INTRODUCTION: Victims of child sexual abuse (CSA) often experience symptoms such
      as recurrent nightmares, which affect their adult life. AIM: This study aimed to
      evaluate the effect of psychotherapy on the quality of life and sleep in a female
      patient with a previous history of CSA. METHODS: The patient was climacteric
      (menopausal transition) and treated in an outpatient clinic. She underwent 40
      sessions of psychotherapy and was evaluated before and after the sessions using
      questionnaires and polysomnography (PSG). MAIN OUTCOME MEASURES: Measurements
      were taken using the following: Kupperman Index (KI), Beck Anxiety Inventory
      (BAI), Beck Depression Inventory (BDI), Prospective and Retrospective Memory
      Questionnaire, and PSG. Reports of dream content were also evaluated during the
      study. RESULTS: After psychotherapeutic intervention, the frequency of nightmares
      and their attendant suffering decreased. Additionally, the context of the
      nightmares changed, and a decrease was noted in the KI, BAI, and BDI parameters.
      The PSG indicated an increase in rapid eye movement sleep. CONCLUSION:
      Psychotherapeutic intervention combined with zolpidem and fluoxetine treatment
      contributed to a resignification of the dreams of a patient with a history of
      CSA. The treatment also improved the quality of her dreams and her quality of
      life.

PMID- 24119036
TI  - Isolation and functional analysis of the KlPDR16 gene.
AB  - The fight against multidrug-resistant pathogens requires an understanding of the
      underlying cellular mechanisms. In this work, we isolate and characterize one of
      the multidrug resistance determinants in Kluyveromyces lactis, the KlPDR16 gene.
      We show that KlPdr16p (345 aa), which belongs to the KlPdr1p regulon, is a
      functional homologue of the Saccharomyces cerevisiae Pdr16p. Deletion of KlPDR16
      resulted in hypersensitivity of K. lactis cells to antifungal azoles, oligomycin,
      rhodamine 6G, 4-nitroquinoline-N-oxide and alkali metal cations. The Klpdr16?
      mutation led to a decreased content of ergosterol in whole-cell extract. In spite
      of the hypersensitivity of Klpdr16? mutant cells to rhodamine 6G and oligomycin,
      the transcript level of the KlPDR5 gene and the rhodamine 6G efflux in the mutant
      was the same as in the parental strain. Increased accumulation of rhodamine 6G in
      Klpdr16? cells indicates that KlPDR16 limits the rate of passive drug diffusion
      across the membrane, without affecting the glucose-induced drug export. The
      results obtained show that KlPDR16, similar to its orthologues in other yeast
      species, influences the passive drug diffusion into the yeast cell. 

PMID- 24119028
TI  - Generation, functional annotation and comparative analysis of black spruce (Picea
      mariana) ESTs: an important conifer genomic resource.
AB  - BACKGROUND: EST (expressed sequence tag) sequences and their annotation provide a
      highly valuable resource for gene discovery, genome sequence annotation, and
      other genomics studies that can be applied in genetics, breeding and conservation
      programs for non-model organisms. Conifers are long-lived plants that are
      ecologically and economically important globally, and have a large genome size.
      Black spruce (Picea mariana), is a transcontinental species of the North American
      boreal and temperate forests. However, there are limited transcriptomic and
      genomic resources for this species. The primary objective of our study was to
      develop a black spruce transcriptomic resource to facilitate on-going functional
      genomics projects related to growth and adaptation to climate change. RESULTS: We
      conducted bidirectional sequencing of cDNA clones from a standard cDNA library
      constructed from black spruce needle tissues. We obtained 4,594 high quality
      (2,455 5' end and 2,139 3' end) sequence reads, with an average read-length of
      532 bp. Clustering and assembly of ESTs resulted in 2,731 unique sequences,
      consisting of 2,234 singletons and 497 contigs. Approximately two-thirds (63%) of
      unique sequences were functionally annotated. Genes involved in 36 molecular
      functions and 90 biological processes were discovered, including 24 putative
      transcription factors and 232 genes involved in photosynthesis. Most abundantly
      expressed transcripts were associated with photosynthesis, growth factors, stress
      and disease response, and transcription factors. A total of 216 full-length genes
      were identified. About 18% (493) of the transcripts were novel, representing an
      important addition to the Genbank EST database (dbEST). Fifty-seven di-, tri-,
      tetra- and penta-nucleotide simple sequence repeats were identified. CONCLUSIONS:
      We have developed the first high quality EST resource for black spruce and
      identified 493 novel transcripts, which may be species-specific related to life
      history and ecological traits. We have also identified full-length genes and
      microsatellite-containing ESTs. Based on EST sequence similarities, black spruce
      showed close evolutionary relationships with congeneric Picea glauca and Picea
      sitchensis compared to other Pinaceae members and angiosperms. The EST sequences
      reported here provide an important resource for genome annotation, functional and
      comparative genomics, molecular breeding, conservation and management studies and
      applications in black spruce and related conifer species.

PMID- 24119037
TI  - Small renal mass biopsy--how, what and when: report from an international
      consensus panel.
AB  - To discuss the use of renal mass biopsy (RMB) for small renal masses (SRMs),
      formulate technical aspects, outline potential pitfalls and provide
      recommendations for the practicing clinician. The meeting was conducted as an
      informal consensus process and no scoring system was used to measure the levels
      of agreement on the different topics. A moderated general discussion was used as
      the basis for consensus and arising issues were resolved at this point. A
      consensus was established and lack of agreement to topics or specific items was
      noted at this point. Recommended biopsy technique: at least two cores, sampling
      different tumour regions with ultrasonography being the preferred method of image
      guidance. Pathological interpretation: 'non-diagnostic samples' should refer to
      insufficient material, inconclusive and normal renal parenchyma. For non
      diagnostic samples, a repeat biopsy is recommended. Fine-needle aspiration may
      provide additional information but cannot substitute for core biopsy. Indications
      for RMB: biopsy is recommended in most cases except in patients with imaging or
      clinical characteristics indicative of pathology (syndromes, imaging
      characteristics) and cases whereby conservative management is not contemplated.
      RMB is recommended for active surveillance but not for watchful-waiting
      candidates. We report the results of an international consensus meeting on the
      use of RMB for SRMs, defining the technique, pathological interpretation and
      indications. 

PMID- 24119038
TI  - The performance of psoriatic arthritis classification criteria in Turkish
      patients with psoriatic arthritis.
AB  - OBJECTIVES: To investigate performance of some of the published psoriatic
      arthritis (PsA) classification criteria as well as Assessment of
      Spondyloarthritis International Society (ASAS) criteria for peripheral
      spondyloarthritis (SpA) in Turkish patients with PsA (in early and late disease
      subgroups). METHODS: Patients were recruited using case report forms and physical
      examination methods proposed by the Anatolian Group for the Assessment in
      Rheumatic Diseases (ANGARD). The Moll and Wright (MW), modified Fournie (MF),
      modified McGonagle (mMG), Vasey and Espinoza (VE), classification of PsA (CASPAR)
      criteria and ASAS criteria were assessed in patients with PsA who were diagnosed
      based on expert opinion. RESULTS: One hundred and twenty-eight patients with PsA
      (58 male, 70 female, mean age 41.8 years) were included. Thirty patients were in
      the early PsA and 98 patients were in the late PsA groups. Diagnostic delay was
      2.6 years. In the 15.6% of patients arthritis developed before the skin findings.
      The proportion of patients fulfilling the MW, MF, mMG, VE, CASPAR and ASAS
      criteria were at a ratio of 90.6%, 82.8%, 62.5%, 84.4%, 96.1% and 76.5%,
      respectively. In early PsA (< 12 months disease duration) the proportions were
      93.4%, 83.3%, 76.7%, 76.7%, 96.7% and 66.6%, respectively. On the other hand, in
      late PsA the proportions were 89.8%, 82.6%, 57.1%, 86.7%, 95.9%, 79.5%,
      respectively. CONCLUSIONS: Even though the sensitivity of PsA classification
      criteria in Turkish patients changes, the CASPAR criteria seems to be more
      prominent among all criteria for both early and late cases with its high
      sensitivity.

PMID- 24119039
TI  - The factor V light chain mediates the binding and endocytosis of plasma-derived
      factor V by megakaryocytes.

PMID- 24119041
TI  - Undercorrection of refractive error and cognitive function: the Beijing Eye Study
      2011.

PMID- 24119042
TI  - Development and evaluation of a novel combinatorial selective enrichment and
      multiplex PCR technique for molecular detection of major virulence-associated
      genes of enterotoxigenic Staphylococcus aureus in food samples.
AB  - AIMS: To develop a multiplex PCR assay coupled with selective enrichment step to
      detect major virulence-associated genes of enterotoxigenic Staphylococcus aureus
      and evaluate the same directly on contaminated food samples. METHODS AND RESULTS:
      The most important virulence-associated genes of Staph. aureus, which are
      commonly related to food safety issues, are targeted in this study. They include
      five major enterotoxigenic genes-sea, seb, sec, seg and sei, tst-which encodes
      TSST-1, mecA-which confer methicillin resistance and coa-for the enzyme coagulase
      along with an internal amplification control (IAC) to rule out false-negative
      result. A modified mannitol salt broth (MSB) supplemented with sodium pyruvate
      was used for selective enrichment of Staph. aureus from food samples prior to
      PCR. Evaluation of efficiency of different media revealed that enrichment of
      samples in modified MSB followed by PCR resulted in specific, sensitive and
      effective amplification of the targeted genes in comparison with other enrichment
      media. Incorporation of bovine serum albumin (BSA) as PCR enhancer improved the
      intensity of amplicons. The standardized multiplex PCR (mPCR) format was able to
      detect all the target genes at a bacterial load of 10(6) CFU ml(-1) in any
      sample. The PCR results were unequivocally correlated with the conventional
      methods when the mPCR format was assessed on a total of 91 Staph. aureus
      isolates. The entire assay was found to be effectual when evaluated on naturally
      contaminated food samples. CONCLUSIONS: The combinatorial approach involving
      selective enrichment followed by mPCR developed in this study was found to be
      effective for the detection of toxigenic Staph. aureus directly from various food
      sources. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed format would find a
      promising application in early detection of food contaminations as well as in the
      diagnosis of food poisoning due to Staph. aureus.

PMID- 24119040
TI  - Glycemic extremes in youth with T1DM: the structural and functional integrity of
      the developing brain.
AB  - The adult brain accounts for a disproportionally large percentage of the body's
      total energy consumption (1). However, during brain development,energy demand is
      even higher, reaching the adult rate by age 2 and increasing to nearly twice the
      adult rate by age 10, followed by gradual reduction toward adult levels in the
      next decade (1,2). The dramatic changes in brain metabolism occurring over the
      first two decades of life coincide with the initial proliferation and then
      pruning of synapses to adult levels.The brain derives its energy almost
      exclusively from glucose and is largely driven by neuronal signaling,
      biosynthesis, and neuroprotection (3-6).Glucose homeostasis in the body is
      tightly regulated by a series of hormones and physiologic responses. As a result,
      hypoglycemia and hyperglycemia are rare occurrences in normal individuals, but
      they occur commonly inpatients with type 1 diabetes mellitus (T1DM) due to a
      dysfunction of peripheral glucose-insulin-glucagon responses and non-physiologic
      doses of exogenous insulin, which imperfectly mimic normal physiology. These
      extremes can occur more frequently in children and adolescents with T1DM due to
      the inadequacies of insulin replacement therapy, events leading to the diagnosis
      [prolonged untreated hyperglycemia and diabetic ketoacidosis (DKA)], and to
      behavioral factors interfering with optimal treatment. When faced with
      fluctuations in glucose supply the metabolism of the body and brain change
      dramatically, largely to conserve resources and, at a cost to other organs, to
      preserve brain function (7). However,if the normal physiological mechanisms that
      prevent these severe glucose fluctuations and maintain homeostasis are impaired,
      neuronal function and potentially viability can be affected (8-11).

PMID- 24119043
TI  - Analysis of decapping scavenger cap complex using modified cap analogs reveals
      molecular determinants for efficient cap binding.
AB  - Decapping scavenger (DcpS) assists in precluding inhibition of cap-binding
      proteins by hydrolyzing cap species remaining after mRNA 3'->5' degradation. Its
      significance was reported in splicing, translation initiation and microRNA
      turnover. Here we examine the structure and binding mode of DcpS from
      Caenorhabditis elegans (CeDcpS) using a large collection of chemically modified
      methylenebis(phosphonate), imidodiphosphate and phosphorothioate cap analogs. We
      determine that CeDcpS is a homodimer and propose high accuracy structural models
      of apo- and m(7) GpppG-bound forms. The analysis of CeDcpS regioselectivity
      uncovers that the only site of hydrolysis is located between the beta and gamma
      phosphates. Structure-affinity relationship studies of cap analogs for CeDcpS
      reveal molecular determinants for efficient cap binding: a strong dependence on
      the type of substituents in the phosphate chain, and reduced binding affinity for
      either methylated hydroxyl groups of m(7) Guo or an extended triphosphate chain.
      Docking analysis of cap analogs in the CeDcpS active site explains how both
      phosphate chain mobility and the orientation in the cap-binding pocket depend on
      the number of phosphate groups, the substituent type and the presence of the
      second nucleoside. Finally, the comparison of CeDcpS with its well known human
      homolog provides general insights into DcpS-cap interactions. 

PMID- 24119044
TI  - The effect of high doses of remifentanil in brain near-infrared spectroscopy and
      in electroencephalographic parameters in pigs.
AB  - OBJECTIVE: To study the effects of a high remifentanil bolus dose on pig's
      electroencephalographic indices and on brain regional and global oxygenation.
      STUDY DESIGN: Prospective experimental study. ANIMALS: Twelve healthy Large-White
      male pigs, age 3 months and weight 26.2 +/- 3.6 kg. METHODS: Anaesthesia was
      induced with intravenous propofol 4 mg kg-1, then maintained with constant rate
      infusions of propofol (15 mg kg-1 hour-1) and remifentanil (0.3 MUg kg-1 minute
      1). Following instrumentation, all pigs received a 5 MUg kg-1 remifentanil bolus.
      The responses of jugular venous oxygen saturation, cardiac output and cerebral
      oxygen saturation to the remifentanil bolus were studied. The Bispectral index,
      spectral edge frequency 95%, total power, approximate entropy and permutation
      entropy were also studied. Repeated measures anova and Pearson correlation were
      used to analyze the effect of remifentanil bolus on these variables until 5
      minutes after the bolus. RESULTS: Cardiac output and cerebral oxygen saturation
      decreased significantly after the remifentanil bolus from 4.6 +/- 0.9 to 3.8 +/-
      1.0 L minute-1 and from 65 +/- 6 to 62 +/- 1% (p < 0.05), respectively. No
      significant changes were observed in the jugular venous oxygen saturation (p >
      0.05) nor in any of the electroencephalogram derived indices (p > 0.05).
      Correlation analysis revealed strong positive significant correlations between
      cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between
      cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001).
      CONCLUSIONS AND CLINICAL RELEVANCE: The effect caused by the remifentanil bolus
      on the brain oxygenation seems to be better reflected by the cerebral oxygen
      saturation than the jugular venous oxygen saturation. The effect of remifentanil
      on the electroencephalogram may not be reflected in indices derived from the
      electroencephalogram, but the potential of the approximate entropy in reflecting
      changes caused by opioids on the electroencephalogram should be further
      investigated.

PMID- 24119045
TI  - Clinical and social correlates of duration of untreated psychosis among adult
      onset psychosis in Hong Kong Chinese: the JCEP study.
AB  - AIM: Understanding factors that contribute to treatment delay would inform early
      detection and intervention strategies in psychotic disorders. However, existing
      data were mixed and primarily conducted among early-onset young patients. We
      examined duration of untreated psychosis (DUP) and its clinical and
      sociodemographic correlates in a large cohort of adult-onset patients with
      psychosis. METHODS: A total of 360 patients with first-onset psychosis aged 26-55
      years were recruited consecutively as part of a controlled study of an early
      psychosis intervention service in Hong Kong Chinese. Demographic,
      sociodemographic and clinical characteristics relating to DUP were assessed
      within 4 months of onset. RESULTS: The population had a mean onset age of 36.6
      years (SD = 8.7). The mean and median DUP were 515 days (SD = 1091) and 93 days
      (inter-quartile range from 20 to 382.3), respectively. Multivariate regression
      analysis suggested that insidious mode of onset, hospitalization, a diagnosis of
      schizophrenia, poorer insight and younger age at onset significantly prolonged
      DUP. DUP was not related to premorbid functioning, family involvement during help
      seeking and living alone. CONCLUSIONS: The initial period of untreated psychosis
      is determined by multiple factors. Whether family involvement is considered a
      kind of social support in shortening or prolonging DUP needs further examination.
      Local early intervention program for psychosis should take reference from these
      findings when formulating personalized plans to reduce delay.

PMID- 24119046
TI  - The effect of gender and gender match on mortality in pediatric heart
      transplantation.
AB  - The effect of organ-recipient gender match on pediatric heart transplant
      mortality is unknown. We analyzed the effects of gender and donor-recipient
      gender matching. Based on Organ Procurement and Transplant Network data, we
      performed a historical cohort study in a population of 3630 heart transplant
      recipients less than 18 years old. We compared unadjusted and adjusted mortality
      by recipient gender, donor gender and between gender-matched and gender
      mismatched recipients. Female recipients had decreased survival compared to male
      recipients (unadjusted hazard ratio [HR] 1.16, confidence interval [CI] 1.02
      1.31; p = 0.020). Organ-recipient gender mismatch did not affect mortality for
      either male or female recipients, though gender-mismatched females had the worst
      survival compared to gender-matched males, who had the best survival (unadjusted
      HR 1.26, CI 1.07-1.49; p = 0.005). After adjustment for other risk factors
      affecting transplant mortality, female recipients had decreased survival compared
      to male recipients (HR 1.27, CI 1.12-1.44; p = 0.020) and gender matching had no
      effect. In conclusion, gender mismatch alone did not increase long-term mortality
      for pediatric heart transplant recipients. However, there may be additive effects
      of gender and gender matching affecting survival. There are insufficient data at
      this time to support that recipient and donor gender should affect heart
      allocation in children. 

PMID- 24119047
TI  - Thermal sealing systems with and without tissue divider for total thyroidectomy.
AB  - BACKGROUND: Sutureless thyroid surgery utilizing thermal sealing is now well
      established. However, incremental advances in technology still require formal
      clinical evaluation in order to ensure that added technology does not compromise
      safety. In this study, we compared a new thermal sealing device incorporating a
      tissue divider (LigaSure Small Jaw) with the device we have previously reported
      for use in total thyroidectomy (LigaSure Precise). METHODS: A cohort study was
      undertaken of 872 total thyroidectomies over a 2-year period. Patients were
      selected for each group on the basis of device availability within four
      institutions and outcomes were obtained from a prospectively maintained database.
      RESULTS: Small Jaw was used in 399 cases and Precise in 473. No significant
      differences between patient demographics (sex, age), operation indication or
      pathology were found. Significantly more Small Jaw operations were performed in
      private versus public hospitals (P < 0.01). Regarding outcomes, there was no
      significant difference in the incidence of any complication (haematoma,
      temporary/permanent hypoparathyroidism or temporary/permanent recurrent laryngeal
      nerve injury). In a subgroup analysis of operations performed in the public
      hospital system, Small Jaw was found to be significantly faster (mean operative
      time: 79 versus 103 min) (95% CI 74-84 and 96-110 min) (P < 0.01). CONCLUSION:
      The incorporation of a tissue divider into thermal sealing devices is efficacious
      and safe, with no compromise in clinical outcome, while providing the added
      benefit of a significant reduction in operative times.

PMID- 24119048
TI  - What do we mean by "older adults' persistent pain self-management"? A concept
      analysis.
AB  - BACKGROUND: No standard definition exists for the concept "persistent pain self
      management" or how it should be defined in relation to older adults. Poorly
      defined concepts can result in misunderstandings in the clinical setting and can
      hinder research through difficulties identifying or measuring the concept.
      OBJECTIVE: To ascertain attributes, referents, antecedents, and consequences of
      the concept older adults' persistent pain self-management and develop a
      theoretical definition. DESIGN: Rodgers evolutionary model of concept analysis
      was used to systematically analyze articles from the academic and grey literature
      (N = 45). Data were extracted using standardized extraction forms and analyzed
      using thematic analysis. FINDINGS: This concept was discussed in three ways: as
      an intervention, in reference to everyday behaviors, and as an outcome. Five
      defining attributes were identified: multidimensional process, personal
      development, active individuals, symptom response, and symptom control. Patients'
      perceived need and ability to manage pain with support from others is necessary
      for pain self-management to occur. Numerous physical, psychological, and social
      health consequences were identified. A theoretical definition is discussed.
      CONCLUSIONS: Our findings have clarified existing use and understanding regarding
      the concept of older adults' persistent pain self-management. We have identified
      three areas for future development: refinement of the attributes of this concept
      within the context of older adults, an exploration of how providers can overcome
      difficulties supporting older adults' persistent pain self-management, and a
      clarification of the overall theoretical framework of older adults' persistent
      pain self-management.

PMID- 24119049
TI  - Sample size verification for clinical trials.
AB  - In this paper, we shall provide simple methods where nonstatisticians can
      evaluate sample size calculations for most large simple trials, as an important
      part of the peer review process, whether a grant, an Institutional Review Board
      review, an internal scientific review committee, or a journal referee. Through
      the methods of the paper, not only can readers determine if there is a major
      disparity, but they can readily determine the correct sample size. It will be of
      comfort to find in most cases that the sample size computation is correct, but
      the implications can be major for the minority where serious errors occur. We
      shall provide three real examples, one where the sample size need was seriously
      overestimated, one (HIP PRO-test of a device to prevent hip fractures) where the
      sample size need was dramatically underestimated, and one where the sample size
      was correct. The HIP PRO case is especially troubling as it went through an NIH
      study section and two peer reviewed journal reports without anyone catching this
      sample size error of a factor of more than five-fold. 

PMID- 24119050
TI  - Preoperative mapping of fistula-in-ano: a new three-dimensional MRI-based
      modelling technique.
AB  - AIM: We aimed to develop an intuitive, interactive, three-dimensional (3D) MRI
      modelling technique to produce a 3D image of fistula-in-ano. METHOD: The 3D model
      was created from standard two-dimensional (2D) MRI sequences to produce an image
      that is anatomically correct. Individual muscle and soft-tissue layers were
      extracted from T1-weighted sequences and fistula pathology from short TI
      inversion recovery (STIR) sequences, to produce two separate volumes. These were
      then fused using postprocessing software (Vitrea Workstation version 6.3) to
      generate a 3D model. RESULTS: The final 3D model was incorporated into a PDF file
      that has an integrated computer aided design (CAD) viewer, allowing the surgeon
      to rotate it in any direction during preoperative planning or whilst in theatre.
      CONCLUSION: As an adjunct to 2D MRI images and the associated radiology report,
      this model communicates the fistula anatomy to the clinician more clearly and
      should be particularly useful in complex cases.

PMID- 24119051
TI  - An ultrasound study of altered hydration behaviour of proteoglycan-degraded
      articular cartilage.
AB  - BACKGROUND: Articular cartilage is a solid-fluid biphasic material covering the
      bony ends of articulating joints. Hydration of articular cartilage is important
      to joint lubrication and weight-wearing. The aims of this study are to measure
      the altered hydration behaviour of the proteoglycan-degraded articular cartilage
      using high-frequency ultrasound and then to investigate the effect of
      proteoglycan (PG) degradation on cartilage hydration. METHODS: Twelve porcine
      patellae with smooth cartilage surface were prepared and evenly divided into two
      groups: normal group without any enzyme treatment and trypsin group treated with
      0.25% trypsin solution for 4 h to digest PG in the tissue. After 40-minute
      exposure to air at room temperature, the specimens were immerged into the
      physiological saline solution. The dehydration induced hydration behaviour of the
      specimen was monitored by the high-frequency (25 MHz) ultrasound pulser/receiver
      (P/R) system. Dynamic strain and equilibrium strain were extracted to
      quantitatively evaluate the hydration behaviour of the dehydrated cartilage
      tissues. RESULTS: The hydration progress of the dehydrated cartilage tissue was
      observed in M-mode ultrasound image indicating that the hydration behaviour of
      the PG-degraded specimens decreased. The percentage value of the equilibrium
      strain (1.84 +/- 0.21%) of the PG-degraded cartilage significantly (p < 0.01)
      decreased in comparison with healthy cartilage (3.46 +/- 0.49%). The histological
      sections demonstrated that almost PG content in the entire cartilage layer was
      digested by trypsin. CONCLUSION: Using high-frequency ultrasound, this study
      found a reduction in the hydration behaviour of the PG-degraded cartilage. The
      results indicated that the degradation of PG decreased the hydration capability
      of the dehydrated tissue. This study may provide useful information for further
      study on changes in the biomechanical property of articular cartilage in
      osteoarthritis.

PMID- 24119052
TI  - Comparative cardiovascular physiology: future trends, opportunities and
      challenges.
AB  - The inaugural Kjell Johansen Lecture in the Zoophysiology Department of Aarhus
      University (Aarhus, Denmark) afforded the opportunity for a focused workshop
      comprising comparative cardiovascular physiologists to ponder some of the key
      unanswered questions in the field. Discussions were centred around three themes.
      The first considered function of the vertebrate heart in its various forms in
      extant vertebrates, with particular focus on the role of intracardiac shunts, the
      trabecular ('spongy') nature of the ventricle in many vertebrates, coronary blood
      supply and the building plan of the heart as revealed by molecular approaches.
      The second theme involved the key unanswered questions in the control of the
      cardiovascular system, emphasizing autonomic control, hypoxic vasoconstriction
      and developmental plasticity in cardiovascular control. The final theme involved
      poorly understood aspects of the interaction of the cardiovascular system with
      the lymphatic, renal and digestive systems. Having posed key questions around
      these three themes, it is increasingly clear that an abundance of new analytical
      tools and approaches will allow us to learn much about vertebrate cardiovascular
      systems in the coming years. 

PMID- 24119053
TI  - Blood pressure variability and left ventricular mass index in children.
AB  - Clinical implications of blood pressure variability (BPV) on subclinical organ
      damage in children are unknown. The authors sought to explore the potential
      utility of two newly derived BPV indices: weighted standard deviation (wBPSD) and
      real average variability (ARV), as well as two standard ambulatory blood pressure
      indices: average 24-hour systolic blood pressure (SBP) and 24-hour SBP load, to
      identify children at high risk for left ventricular (LV) hypertrophy (LVH). The
      study group consisted of 67 consecutive children who were referred to our
      institution for evaluation of suspected hypertension. LV mass was estimated by M
      mode echocardiography using Devereux's formula according to the Penn convention
      and indexed for height(2.7) . We found a statistically significant, positive
      correlation between 24-hour wBPSD and LV mass index (LVMI) (rho=0.389; P=.002)
      and no correlation between 24-hour ARV and LVMI (P>.05). However, partial
      correlation analysis of 24-hour wBPSD adjusted for body mass index (BMI) and LVMI
      showed only a weak correlation (rho=0.3; P=.022). By using multiple linear
      regression analysis in a model with LVMI as a dependent variable and 24-hour
      wBPSD, 24-hour ARV, and BMI as independent variables, only BMI showed
      statistically significant independent positive associations with LVMI (P=.028).
      Results of our study showed that currently used BPV indices (24-hour wBPSD and 24
      hour ARV) are not clinically reliable parameters to identify children at risk for
      LVH. Apparent contribution of the 24-hour wBPSD parameter to LVMI is negligible
      and is secondary to its close correlation with BMI (rho=0.335 P=.009). 

PMID- 24119054
TI  - Evaluation of nail fold capillaroscopy findings in patients with primary biliary
      cirrhosis.
AB  - AIM: Some patients with primary biliary cirrhosis (PBC) experience Raynaud's
      phenomenon. The objective of this study was to clarify the relationships between
      nail fold capillaroscopy findings and clinical presentations of PBC. METHODS: A
      total of 70 patients with PBC and 57 patients with non-PBC liver diseases,
      including 44 patients with chronic viral hepatic disease, eight with autoimmune
      hepatitis and five with non-alcoholic fatty liver disease, were included in this
      study. Nail fold capillaroscopy findings were classified as normal or abnormal
      and were further graded as mild, moderate or severe, and the relationships
      between frequency of abnormal blood vessel and their clinical presentations were
      examined. RESULTS: The frequency of abnormal nail fold capillaroscopy findings
      was significantly higher in PBC patients (54.3%) than in patients with non-PBC
      liver disease (13.8%) (P < 0.01). These abnormal findings observed in PBC
      patients were graded as mild in 15 patients, moderate in 18 patients and severe
      in five patients. Significantly more PBC patients with abnormal capillaroscopy
      findings (19/38, 50%) were positive for anticentromere antibody than were those
      with normal capillaroscopy findings (3/32, 9.4%) (P < 0.01). CONCLUSION: PBC
      patients had significantly higher frequency of abnormal nail fold capillaroscopy
      findings than did patients with non-PBC liver disease.

PMID- 24119055
TI  - Dispersal limitation structures fungal community assembly in a long-term glacial
      chronosequence.
AB  - Microbial communities in soil mediate biogeochemical processes; however,
      understanding forces shaping their composition and function remains a gap in our
      ecological knowledge. We investigated phylogenetic turnover and functional gene
      composition of saprotrophic fungi along a 4000-year glacial chronosequence. A
      direct relationship between beta-diversity and geographic distance, a proxy for
      time since deglaciation, indicated that dispersal limitation shapes saprotrophic
      fungal communities. Further, we infer that dispersal limitation may also
      influence fungal functional properties as metabolic potential and functional
      richness increased with site age. Despite attempts to minimize environmental
      variation, a direct relationship between beta-diversity and biogeochemical
      differences across sites indicated that environmental filtering further shapes
      fungal community composition. However, environmental filtering was overshadowed
      by the effect of dispersal limitation when tested by multiple regression. Fungal
      beta-diversity and composition of functional genes involved in plant litter decay
      were unrelated, suggesting that functional traits are not phylogenetically
      conserved across this chronosequence. Our study suggests that dispersal
      limitation operates in structuring present-day fungal community composition and
      functional potential. Further, we demonstrate the need to integrate functional
      and phylogenetic approaches to more accurately portray microbial communities and
      their functional capacities. 

PMID- 24119056
TI  - Reliability assessment of null allele detection: inconsistencies between and
      within different methods.
AB  - Microsatellite loci are widely used in population genetic studies, but the
      presence of null alleles may lead to biased results. Here, we assessed five
      methods that indirectly detect null alleles and found large inconsistencies among
      them. Our analysis was based on 20 microsatellite loci genotyped in a natural
      population of Microtus oeconomus sampled during 8 years, together with 1200
      simulated populations without null alleles, but experiencing bottlenecks of
      varying duration and intensity, and 120 simulated populations with known null
      alleles. In the natural population, 29% of positive results were consistent
      between the methods in pairwise comparisons, and in the simulated data set, this
      proportion was 14%. The positive results were also inconsistent between different
      years in the natural population. In the null-allele-free simulated data set, the
      number of false positives increased with increased bottleneck intensity and
      duration. We also found a low concordance in null allele detection between the
      original simulated populations and their 20% random subsets. In the populations
      simulated to include null alleles, between 22% and 42% of true null alleles
      remained undetected, which highlighted that detection errors are not restricted
      to false positives. None of the evaluated methods clearly outperformed the others
      when both false-positive and false-negative rates were considered. Accepting only
      the positive results consistent between at least two methods should considerably
      reduce the false-positive rate, but this approach may increase the false-negative
      rate. Our study demonstrates the need for novel null allele detection methods
      that could be reliably applied to natural populations.

PMID- 24119057
TI  - Prevalence and correlates of fecal incontinence among nursing home residents: a
      population-based cross-sectional study.
AB  - BACKGROUND: Fecal incontinence is highly prevalent among nursing home residents.
      Previous nursing home studies have identified co-morbidity associated with fecal
      incontinence, but as this population is increasingly old and frail, we wanted to
      see if the rate of fecal incontinence had increased and to investigate correlates
      of fecal incontinence further. METHODS: Cross-sectional study of the entire
      nursing home population in one Norwegian municipality. Registered nurses filled
      in a questionnaire for all residents in the municipality (980 residents aged
      >=65). Statistical methods used are descriptive statistics, binary logistic
      regression and multivariable logistic regression. RESULTS: The response rate of
      the study was 90.3%. The prevalence of fecal incontinence was 42.3%. In
      multivariable analysis of FI, residents with diarrhea (OR 7.33, CI 4.39-12.24),
      urinary incontinence (OR 2.77, CI 1.73-4.42) and dementia (OR 2.17, CI 1.28-3.68)
      had higher odds of having fecal incontinence compared to those without the
      condition. Residents residing in a nursing home between 4-5 years had higher odds
      of having fecal incontinence compared to residents who had stayed under a year
      (OR 2.65, CI 1.20-5.85). Residents with deficiency in feeding (2.17, CI 1.26
      3.71), dressing (OR 4.03, CI 1.39-11.65), toilet use (OR 7.37, CI 2.65-20.44) and
      mobility (OR 2.54, CI 1.07-6.00) had higher odds of having fecal incontinence
      compared to residents without deficiencies in activities of daily living (ADL).
      Needing help for transfer between bed and chair was a protective factor for fecal
      incontinence compared to residents who transferred independently (OR 0.49, CI
      0.26-0.91). CONCLUSIONS: Fecal incontinence is a prevalent condition in the
      nursing home population and is associated with ADL decline, frailty, diarrhea and
      quality of care. This knowledge is important for staff in nursing home in order
      to provide the best treatment and care for residents with fecal incontinence.

PMID- 24119058
TI  - Incidence and mortality trends for biliary tract cancers in Austria.
AB  - BACKGROUND & AIMS: The epidemiology of biliary tract cancers (BTC) varies between
      geographical regions and has changed over time globally. We investigated the
      incidence and mortality trends of patients diagnosed with BTC over a 20-year
      period in Austria. METHODS: Patients diagnosed with intrahepatic
      (iCCC)/extrahepatic cholangiocarcinoma (eCCC), ampullary carcinoma, gall bladder
      carcinoma (GBC), overlapping lesions or unspecified carcinomas of the biliary
      tract and liver were included. Data on age-adjusted incidence were obtained from
      the Austrian National Cancer Registry which compiles data on all newly diagnosed
      cancers. Data on age-adjusted mortality were obtained from the national death
      registry (Statistics Austria). RESULTS: Between 1990 and 2009, 15201 patients
      were diagnosed with BTC (m/f=42/58%; mean age, 73 years). The median survival of
      all patients with BTC was 4.8 months with a 1-/5-year survival rate of 31%/10%.
      In iCCC, the incidence and mortality rates increased from 1990 to 2009 in both
      men and women while in eCCC, the incidence and mortality rates decreased over
      time in both sexes. In ampullary carcinoma, the incidence slightly decreased in
      men and remained stable in women. The mortality rate remained stable in both
      sexes. In GBC, the age-adjusted incidence and mortality rates dramatically
      decreased in both sexes. CONCLUSIONS: GBC and iCCC were the most common entities
      amongst BTC. While incidence and mortality rates of iCCC increased in men and
      women over time, incidence and mortality rates of eCCC and GBC decreased in both
      sexes. Other carcinomas of the biliary tract i.e. ampullary carcinoma were rarely
      diagnosed.

PMID- 24119059
TI  - WASH-driven actin polymerization is required for efficient mycobacterial
      phagosome maturation arrest.
AB  - Pathogenic mycobacteria survive in phagocytic host cells primarily as a result of
      their ability to prevent fusion of their vacuole with lysosomes, thereby avoiding
      a bactericidal environment. The molecular mechanisms to establish and maintain
      this replication compartment are not well understood. By combining molecular and
      microscopical approaches we show here that after phagocytosis the actin
      nucleation-promoting factor WASH associates and generates F-actin on the
      mycobacterial vacuole. Disruption of WASH or depolymerization of F-actin leads to
      the accumulation of the proton-pumping V-ATPase around the mycobacterial vacuole,
      its acidification and reduces the viability of intracellular mycobacteria. This
      effect is observed for M. marinum in the model phagocyte Dictyostelium but also
      for M. marinum and M. tuberculosis in mammalian phagocytes. This demonstrates an
      evolutionarily conserved mechanism by which pathogenic mycobacteria subvert the
      actin-polymerization activity of WASH to prevent phagosome acidification and
      maturation, as a prerequisite to generate and maintain a replicative niche.

PMID- 24119061
TI  - Aging and differentiation in yeast populations: elders with different properties
      and functions.
AB  - Over the past decade, it has become evident that similarly to cells forming
      metazoan tissues, yeast cells have the ability to differentiate and form
      specialized cell types. Examples of yeast cellular differentiation have been
      identified both in yeast liquid cultures and within multicellular structures
      occupying solid surfaces. Most current knowledge on different cell types comes
      from studies of the spatiotemporal internal architecture of colonies developing
      on various media. With a few exceptions, yeast cell differentiation often
      concerns nongrowing, stationary-phase cells and leads to the formation of cell
      subpopulations differing in stress resistance, cell metabolism, respiration, ROS
      production, and others. These differences can affect longevity of particular
      subpopulations. In contrast to liquid cultures, where various cell types are
      dispersed within stationary-phase populations, cellular differentiation depends
      on the specific position of particular cells within multicellular colonies.
      Differentiated colonies, thus, resemble primitive multicellular organisms, in
      which the gradients of certain compounds and the position of cells within the
      structure affect cellular differentiation. In this review, we summarize and
      compare the properties of diverse types of differentiated chronologically aging
      yeast cells that have been identified in colonies growing on different media, as
      well as of those found in liquid cultures. 

PMID- 24119060
TI  - Adaptations for insect-trapping in brood-site pollinated Colocasia (Araceae).
AB  - The Araceae include both taxa with rewarding and deceptive trap pollination
      systems. Here we report on a genus in which rewarding and imprisonment of the
      pollinators co-occur. We studied the pollination of four species of Colocasia in
      Southwest China and investigated the morpho-anatomical adaptations of the spathe
      related to the attraction and capture of pollinators. All four species were
      pollinated by drosophilid flies of the genus Colocasiomyia. The flies are
      temporally arrested within the inflorescence and departure is only possible after
      pollen release. Trapping of the flies is accomplished by the closure of the
      spathe during anthesis. Moreover, in two species the spathe is covered with
      papillate epidermal cells known to form slippery surfaces in deceptive traps of
      Araceae. However, in Colocasia the papillae proved not slippery for the flies.
      The morpho-anatomical properties of the spathe epidermis indicate that it is an
      elaborate osmophore and serves for the emission of odours only. Despite its
      similarity to deceptive traps of other aroids, Colocasia and Colocasiomyia have a
      close symbiotic relationship, as the attracted flies use the inflorescence as a
      site for mating and breeding. The trap mechanism has presumably evolved
      independently in Colocasia and is supposed to facilitate more efficient pollen
      export.

PMID- 24119062
TI  - Potential of a 70 kDa IL-10-like factor in synovial fluid from rheumatoid
      arthritis patients to augment superoxide generation by human neutrophils.
AB  - AIM: To elucidate the role of polymorphonuclear leukocytes (PMNs) in joint
      destruction during the inflammatory process in rheumatoid arthritis (RA) as
      related to superoxide generation. METHODS: Superoxide generation by human
      peripheral PMNs was measured by using a water-soluble formazan dye, 2-(4
      iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium
      salt, under PMN stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP)
      and cytochalasin B. Factors in synovial fluids (SF) from RA patients that may
      augment PMN superoxide generation were characterized via high-performance liquid
      chromatography and isoelectric focusing. RESULTS: The formazan dye allowed
      measurement of superoxide generated in the xanthine-xanthine oxidase system and
      by PMNs stimulated by cytochalasin B and fMLP in the presence of the intermediate
      electron transporter phenazine methosulfate. By using chromatography and
      electrophoresis, an RA-SF protein with an apparent molecular size of 70 kDa and
      an isoelectric point of 8.3 was isolated and was demonstrated to increase
      superoxide generation by PMNs. The factor was heat-labile and susceptible to
      protease treatment. This enhancing activity of the factor was absorbed by human
      PMNs and was somewhat immunoadsorbed with a specific monoclonal antibody against
      interleukin (IL)-10. CONCLUSION: The 70-kDa protein factor in RA-SF increased
      superoxide generation by human PMNs, which suggests the possibility of its being
      related to IL-10. This factor may have a pathological role in RA joint
      destruction caused by PMNs and coinciding with rheumatoid inflammation, which
      suggests that PMNs, via superoxide generation, play an important role in RA joint
      destruction. IL-10 therefore likely has biological activity toward PMNs during
      synovial inflammatory chain reactions in RA.

PMID- 24119063
TI  - Selective D-dimer testing for the diagnosis of acute deep vein thrombosis: a
      validation study.

PMID- 24119064
TI  - The effects of two 10% carbamide peroxide nightguard bleaching agents, with and
      without desensitizer, on enamel and sensitivity: an in vivo study.
AB  - OBJECTIVES: This study aimed to compare the effects of two 10% carbamide peroxide
      (CP) agents with or without desensitizers on tooth sensitivity, colour and enamel
      morphological changes. METHODS: Twenty subjects used a 10% carbamide peroxide gel
      with or without fluoride and potassium nitrate for 2 weeks. Sensitivity,
      spectrophotometric evaluation of colour and morphological analyses of replicas
      with scanning electron microscope (SEM) were performed before and after
      treatment. All data were analysed statistically. RESULTS: Both bleaching agents
      induced sensitivity; however, the 10% CP bleaching agent with fluoride and
      potassium nitrate produced significantly lower sensitivity (P < 0.05) than the
      bleaching product without desensitizing agents. In spectrophotometric evaluation,
      no difference in bleaching effectiveness was found between the tested bleaching
      gels, and the SEM analysis confirmed the absence of relevant alterations of the
      enamel surface in both groups. CONCLUSION: The use of 10% carbamide peroxide gel
      with fluoride and potassium nitrate reduced the incidence of sensitivity during
      the bleaching treatment compared to a bleaching agent that did not contain
      desensitizing agents. The bleaching effectiveness of the tested products was
      comparable.

PMID- 24119065
TI  - Correlation of magnetic resonance imaging optic nerve parameters to optical
      coherence tomography and the visual field in glaucoma.
AB  - BACKGROUND: To determine the viability of using magnetic resonance imaging
      measurement of optic nerve morphology as an objective analysis of glaucomatous
      damage. DESIGN: Retrospective study conducted at Tohoku University Hospital.
      PARTICIPANTS: Thirty-eight eyes of 19 patients with open-angle glaucoma. METHODS:
      Patients were scanned with T2-weighted and 3-T diffusion tensor magnetic
      resonance imaging, and parameters of the optic nerve, including fractional
      anisotropy, apparent diffusion coefficient and cross-sectional area, were
      determined. Conventional parameters of glaucomatous damage, including
      circumpapillary and macular retinal nerve fibre layer thickness, and mean
      deviation and average total deviation of the central 16 test points from the
      Humphrey Field Analyzer, were then compared with the magnetic resonance imaging
      derived parameters. Spearman's coefficient of correlation was calculated to
      determine the significance of the correlation. MAIN OUTCOME MEASURE: Correlation
      coefficient between the magnetic resonance imaging parameters and the parameters
      of glaucomatous damage. RESULTS: Mean deviation was significantly correlated with
      all magnetic resonance imaging parameters (fractional anisotropy: r = 0.53,
      apparent diffusion coefficient: r = -0.44, cross-sectional area: r = 0.70).
      Circumpapillary retinal nerve fibre layer thickness was significantly correlated
      with fractional anisotropy (r = 0.60) and cross-sectional area (r = 0.47), but
      not apparent diffusion coefficient (r = -0.29). Central macular function and
      macular retinal nerve fibre layer thickness were also significantly correlated
      with magnetic resonance imaging parameters. CONCLUSIONS: Optic nerve magnetic
      resonance imaging parameters were significantly correlated to glaucomatous
      damage. Magnetic resonance imaging analysis of the optic nerve may, thus, have
      value as an objective instrument to assess glaucomatous degeneration, including
      the function of the macula.

PMID- 24119067
TI  - Evidence for reduced neuromuscular function in men with a history of androgen
      deprivation therapy for prostate cancer.
AB  - BACKGROUND: Indices of body composition and muscular strength were compared
      between men with prostate cancer (PCa) treated with androgen deprivation therapy
      (ADT) and asymptomatic matched men. METHODS: Nine subjects aged 63-83 years with
      PCa who received ADT (PCa+ADT; duration 6-180 months) and 11 asymptomatic aged
      matched eugonadal men (HM) aged 59-80 years were assessed for prostate-specific
      antigen (PSA) and total testosterone (TT). Total body non-osseous lean mass
      (TBLM) and right thigh non-osseous fat-free mass (RTLM) were assessed using dual
      energy X-ray absorptiometry. Peak torque of the right knee extensors at 0 degrees
      s(-1) (ISO) and 60 degrees  s(-1) (CON), maximal handgrip strength of the
      dominant hand (MHS) and whole-body strength (WBS) were assessed. ISO and CON per
      unit mass of RTLM and MHS and WBS per unit mass of TBLM were calculated. RESULTS:
      Age, height, mass, body mass index and prostate-specific antigen were comparable
      between groups (P>0.05), while TT was lower in PCa+ADT (P<0.01). RTLM was similar
      between groups (P>=0.075). Absolute ISO and CON were lower for PCa+ADT (P<0.01)
      as were CON per unit of RTLM and ISO per unit of RTLM (P<0.05). Absolute MHS, WBS
      and MHS per unit of TBLM and WBS per unit of TBLM were lower for PCa+ADT (P<0.01;
      P<0.05). CONCLUSIONS: Men with PCa who receive ADT experience significant losses
      in whole-body muscular strength compared with asymptomatic age-matched men, which
      may impair functional capacity. These losses in muscular strength appear to
      involve neuromuscular mechanisms that are yet to be identified.

PMID- 24119066
TI  - Large-scale polymorphism discovery in macaque G-protein coupled receptors.
AB  - BACKGROUND: G-protein coupled receptors (GPCRs) play an inordinately large role
      in human health. Variation in the genes that encode these receptors is associated
      with numerous disorders across the entire spectrum of disease. GPCRs also
      represent the single largest class of drug targets and associated pharmacogenetic
      effects are modulated, in part, by polymorphisms. Recently, non-human primate
      models have been developed focusing on naturally-occurring, functionally-parallel
      polymorphisms in candidate genes. This work aims to extend those studies broadly
      across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing
      44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus
      macaques, and 32 cynomolgus macaques (M. fascicularis). RESULTS: Using the
      Agilent target enrichment system, capture baits were designed for GPCRs off the
      human and rhesus exonic sequence. Using next generation sequencing technologies,
      nearly 25,000 SNPs were identified in coding sequences including over 14,000 non
      synonymous and more than 9,500 synonymous protein-coding SNPs. As expected,
      regions showing the least evolutionary constraint show greater rates of
      polymorphism and greater numbers of higher frequency polymorphisms. While the
      vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and
      2,900 synonymous SNPs were found in multiple individuals. CONCLUSIONS: In all
      three populations, polymorphism and divergence is highly concentrated in N
      terminal and C-terminal domains and the third intracellular loop region of GPCRs,
      regions critical to ligand-binding and signaling. SNP frequencies in macaques
      follow a similar pattern of divergence from humans and new polymorphisms in
      primates have been identified that may parallel those seen in humans, helping to
      establish better non-human primate models of disease.

PMID- 24119068
TI  - A creative therapy in treating cavernous hemangioma of penis with copper wire.
AB  - INTRODUCTION: Cavernous hemangiomas of penis are rare benign lesions infrequently
      described in the literature. No completely satisfactory treatment has been found
      to correct the cosmetic deformities especially the extensive hemangiomas of
      corpus penis. AIM: In light of the promising application of copper wire/needle in
      vascular malformations, we began a clinical study to investigate the safety,
      feasibility, and cosmetic effect of copper wire therapy in treating cavernous
      hemangioma of penis. METHODS: Seven patients ranging in age from 12 to 32 years
      with penile cavernous hemangiomas entered our study from 2005 to 2011. All
      patients received treatments with percutaneous copper wires. MAIN OUTCOME
      MEASURES: Perioperative data including mean operation time, estimated blood loss,
      length of copper wire retention, and length of hospital stay were analyzed. All
      possible complications were noted, and cosmetic result was evaluated. Patients
      were followed up after discharge from the hospital. RESULTS: All operations were
      successful, and no obvious complications were observed. The patients were
      satisfied with the aesthetic results. Follow-up time ranged from 1 to 5 years.
      Recurrence was discovered in a patient with the largest lesion of corpus penis 2
      months after the treatment. Secondary procedure was carried out with the same
      technique, and no lesions were found later. CONCLUSIONS: The shortage of studies
      on this topic prevented us from defining a therapeutic reference standard. The
      results of our study confirmed that copper wire therapy was a simple, safe, and
      useful option for penile cavernous hemangioma.

PMID- 24119069
TI  - Optic nerve hypoplasia in children and adolescents; prevalence, ocular
      characteristics and behavioural problems.
AB  - PURPOSE: To report prevalence, ocular characteristics and coexisting behavioural
      problems in children and adolescents with optic nerve hypoplasia (ONH), which is
      a common cause of visual impairment in children in western countries, often
      associated with neurological or endocrinological problems and where autism has
      been reported in severe cases with blindness. METHODS: This is a population-based
      cross-sectional study of patients <20 years of age who had been diagnosed with
      ONH and lived in the county of Stockholm in December 2009. Ophthalmological
      assessments including fundus photographs with optic disc analyses were made. A
      questionnaire was used to screen for behaviour and development. RESULTS: The
      prevalence of ONH in all living children <18 years of age in Stockholm was
      17.3/100 000 with a prevalence of visual impairment (<0.3) of 3.9/100 000. In
      total, 66 patients, median age 9.3 years (0.6-19.4), 36 with bilateral and 30
      with unilateral ONH, were included in the current study; 53 were re-examined
      clinically, group A, and 13 agreed to retrospective analyses of existing medical
      records, group B. Analyses of the optic discs were made in fundus photographs
      from 53 patients comparing a semi-automated (Retinal Size Tool) and a manual
      method (Zeki). There was a strong curvilinear correlation (r(S)  = -0.91 p <
      0.0001 for both eyes). Behavioural problems were more common (p < 0.05) in
      bilateral ONH. CONCLUSION: Optic nerve hypoplasia is a common ocular malformation
      with a prevalence of 17.3/100 000 children and adolescents <18 years of age in
      Stockholm. Unilateral ONH seems as common as bilateral.

PMID- 24119070
TI  - An anesthetic protocol for adult heartworms removal in two cases of canine caval
      syndrome.

PMID- 24119071
TI  - Elizabethkingia species sepsis after lung transplantation: case report and
      literature review.
AB  - Elizabethkingia species are environmental bacteria that rarely cause infection in
      neonates and immunocompromised adults, usually as part of nosocomial outbreaks.
      We report an isolated fatal case of disseminated Elizabethkingia species
      infection in a lung transplant recipient and review the literature of this
      bacterial infection in transplant recipients. 

PMID- 24119072
TI  - Predictive value of C-reactive protein with Alvarado score in acute appendicitis.
AB  - BACKGROUND: The aim of the study was to evaluate whether C-reactive protein (CRP)
      level on admission could aid the diagnostic accuracy of Alvarado score in acute
      appendicitis. METHODS: We retrospectively evaluated hospital records and database
      of 234 patients (men 116, women 118, median age 28 years, range 15-87 years) who
      underwent appendicectomy for acute appendicitis. Patients were categorized into
      three groups retrospectively based on the Alvarado score. Group I: score 7-10 (n
      = 155), group II: score 4-6 (n = 71), group III: score less than 3 (n = 10).
      Negative (NPV) and positive predictive values (PPV) of CRP was calculated.
      RESULTS: Overall, 169 of 234 (72.2%) had histopathological confirmation of acute
      appendicitis. The predicted accuracy of Alvarado score was 84.5% in group I,
      50.7% in group II and 25% in group III. The PPV of high CRP and NPV of normal CRP
      for group I was 88% and 36.4%, in group II, 63% and 72%, in group III, 33% and
      86%, respectively. CONCLUSION: The Alvarado score and CRP taken together improve
      the predictive value of diagnosing acute appendicitis. Having a normal CRP in the
      equivocal group of Alvarado 4-6, should be further evaluated by advanced imaging
      before proceeding to appendicectomy.

PMID- 24119073
TI  - Recent developments in the use of viability dyes and quantitative PCR in the food
      microbiology field.
AB  - The increase in foodborne outbreaks highlights the need for rapid, sensitive and
      specific methods for food safety monitoring, enabling specific detection and
      quantification of viable foodborne pathogens. Real-time PCR (qPCR) combined with
      the use of viability dyes, recently introduced, fulfils all these requirements.
      The strategy relies on the use of DNA-binding molecules such as propidium
      monoazide (PMA) or ethidium monoazide (EMA) as sample pretreatment previous to
      the qPCR. These molecules permeate only membrane-compromised cells and have
      successfully been applied for different types of foodborne pathogens, including
      bacteria and viruses. Moreover, those dyes have been explored to monitor
      different food manufacturing processes as an alternative to classical cultural
      methods. In this review, state-of-the-art information regarding viability PCR (v
      PCR) is compiled. 

PMID- 24119074
TI  - Urinary saturation: casual or causal risk factor in urolithiasis?
AB  - OBJECTIVE: To assess (i) the extent to which urinary supersaturation (SS) has
      successfully discriminated between stone formers and healthy individuals (N),
      (ii) whether absolute SS has diagnostic worth and (iii) whether high SS is the
      fundamental cause of stone formation per se. MATERIALS AND METHODS: Google
      Scholar was used to identify studies in which urinary compositional data had been
      determined. In those cases where SS values were not given, or where other risk
      indices had been reported, they were (re-)calculated. Collected data were termed
      'global' but were then 'filtered' according to stone type and protocols used for
      SS calculations. SS distribution plots for calcium oxalate, brushite and uric
      acid were constructed. Data were statistically analysed using the unpaired t-test
      and Mann-Whitney test. RESULTS: In all, 47 studies yielded 123 SS values for
      healthy individuals and 122 values for stone formers. The mean and median SS
      values were significantly greater in stone formers compared with healthy
      individuals in all but one of the comparisons. Wide variations in SS occurred for
      healthy individuals and stone formers. The two groups could not be separated.
      CONCLUSIONS: Absolute SS has no diagnostic worth. It is impossible to quantify
      the meaning of a 'high' SS value. Urines cannot be identified as originating from
      healthy individuals or stone formers based on their SS. SS should be determined
      in clinical and research settings for relative comparisons during the assessment
      of treatment efficacies. This study provides a compelling argument for SS being a
      casual factor rather than a causal one.

PMID- 24119075
TI  - Solid-phase bead-based assays limitations are not restricted to interlaboratory
      variability.

PMID- 24119076
TI  - The prognostic value of tumour regression grade following neoadjuvant
      chemoradiation therapy for rectal cancer.
AB  - AIM: To date, there is no uniform consensus on whether tumour regression grade
      (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of
      standardization of TRG grading is a major source of variability in published
      studies. The aim of this study was to evaluate the prognostic impact of TRG in a
      cohort of patients with locally advanced rectal cancer treated with neoadjuvant
      chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four
      TRG systems modified from the Mandard TRG system and applied them to the cohort
      to assess which TRG system is most informative. METHOD: One-hundred and fifty
      three patients with a T3/T4 and/or a node-positive rectal cancer underwent
      neoadjuvant 5-fluorouracil-based CRT followed by surgical resection. RESULTS:
      Thirty-six (23.5%) patients achieving complete pathological response (ypCR) had a
      5-year disease-free survival (DFS) rate of 100% compared with a DFS rate of 74%
      for 117 (76.5%) patients without ypCR (P = 0.003). The Royal College of
      Pathologists (RCPath) TRG best condenses the Mandard five-point TRG by
      stratifying patients into three groups with distinct 5-year DFS rates of 100%,
      86% and 67%, respectively (P = 0.001). In multivariate analysis, pathological
      nodal status and circumferential resection margin (CRM) status, but not TRG,
      remained significant predictors of DFS (P = 0.002, P = 0.035 and P = 0.310,
      respectively). CONCLUSION: Our findings support the notion that ypCR status,
      nodal status after neoadjuvant CRT and CRM status, but not TRG, are predictors of
      long-term survival in patients with locally advanced rectal cancer.

PMID- 24119077
TI  - Pain is independently associated with impaired physical function in HIV-infected
      patients.
AB  - INTRODUCTION: Human immunodeficiency virus (HIV)-infected patients in the current
      treatment era can achieve normal life expectancies but experience a high degree
      of medical and psychiatric comorbidity. Impaired physical function and pain,
      often in the context of mood disorders and substance abuse, are common in HIV
      infected patients. The objective of this study was to investigate the
      relationship of pain, a modifiable condition, to functional impairment in HIV
      infected patients, independent of mood disorders and substance abuse. METHODS:
      Participants in a prospective cohort of HIV-infected patients at the University
      of Alabama at Birmingham were included. Patient-reported outcome measures were
      used to cross-sectionally assess pain and physical function (EuroQOL), mood
      disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable
      models were built with pain as the principal independent variable of interest and
      three domains of physical function (mobility, self-care, and usual activities) as
      outcomes. Covariates included mood, substance abuse, age, race, sex, insurance
      status, HIV transmission risk factor, and CD4+ T-cell count. RESULTS: Among 1,903
      participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157
      (8.4%) reported current substance abuse. In multivariable models, pain was
      independently associated with increased odds of impairment in all three domains
      of physical function investigated-mobility (aOR 10.5, 95% CI 7.6-14.6), self-care
      (aOR 4.1, 95% CI 2.2-7.4), and usual activities (aOR 5.4, 95% CI 4.0-7.4).
      DISCUSSION: Pain was associated with substantially increased odds of impairment
      in physical function. Pain should be an important consideration in HIV primary
      care. Interventions to address pain and impaired physical function should be
      investigated.

PMID- 24119080
TI  - Lipotoxicity and the role of maternal nutrition.
AB  - Intrauterine malnutrition predisposes the offspring towards the development of
      type 2 diabetes and cardiovascular disease. To explain this association, the
      Developmental Origins of Health and Disease hypothesis was introduced, meaning
      that subtle environmental changes during embryonic and foetal development can
      influence post-natal physiological functions. Different mechanisms, including
      epigenetics, are thought to be involved in this foetal programming, but the link
      between epigenetics and disease is missing. There is increasing evidence that
      ectopic lipid accumulation and/or lipotoxicity is induced by foetal programming.
      The aim of this review is to provide insights into the mechanisms underlying
      lipotoxicity through programming, which contributes to the increase in hepatic
      and cardiac metabolic risk. 

PMID- 24119078
TI  - Recombinant DNA production of spider silk proteins.
AB  - Spider dragline silk is considered to be the toughest biopolymer on Earth due to
      an extraordinary combination of strength and elasticity. Moreover, silks are
      biocompatible and biodegradable protein-based materials. Recent advances in
      genetic engineering make it possible to produce recombinant silks in heterologous
      hosts, opening up opportunities for large-scale production of recombinant silks
      for various biomedical and material science applications. We review the current
      strategies to produce recombinant spider silks. 

PMID- 24119081
TI  - The AViKA (Adding Value in Knee Arthroplasty) postoperative care navigation
      trial: rationale and design features.
AB  - BACKGROUND: Utilization of total knee arthroplasty is increasing rapidly. A
      substantial number of total knee arthroplasty recipients have persistent pain
      after surgery. Our objective was to design a randomized controlled trial to
      establish the efficacy of a motivational-interviewing-based telephone
      intervention aimed at improving patient outcomes and satisfaction following total
      knee arthroplasty. METHODS/DESIGN: The study was conducted at Brigham and Women's
      Hospital in Boston, Massachusetts. The study focused on individuals 40 years or
      older with a primary diagnosis of osteoarthritis who were scheduled for total
      knee arthroplasty. The study compared two management strategies over the first
      six months postoperatively: 1) enhanced postoperative care with frequent follow
      up by a care navigator; 2) usual postoperative care. Those who were randomized
      into the enhanced postoperative care arm received ten calls from a trained non
      clinician care navigator over the first six postoperative months. The navigator
      used motivational interviewing techniques to engage patients in discussions
      related to their rehabilitation goals, including patient's plans for and
      confidence in achieving those goals. Patients in the usual care arm received
      standard postoperative management and received no navigator phone calls. Patients
      in both arms were assessed at baseline, three months, and six months
      postoperatively. DISCUSSION: The primary outcome of the study was improvement in
      function as measured by the difference in Western Ontario and McMaster
      Universities Osteoarthritis Index function score between preoperative (baseline)
      status and six months postoperatively. Data were collected to identify factors
      that may be related to total knee arthroplasty outcomes, including preoperative
      pain, pain catastrophizing, self-efficacy, and depression. A formal economic
      analysis is also planned to determine the cost-effectiveness of the care
      navigator as a component of total knee arthroplasty care. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01540851.

PMID- 24119083
TI  - Correlation between tuberous sclerosis complex 2 and glycogen synthase kinase 3
      beta levels, and outcomes of patients with hepatocellular carcinoma treated by
      hepatectomy.
AB  - AIM: Tuberous sclerosis complex 2 (TSC2), a tumor suppressor, may play an
      essential role in the regulation of cell growth and cell survival under energy
      stress conditions. In addition, TSC2 may act in concert with Wnt and energy
      signals by additional phosphorylation of glycogen synthase kinase 3beta
      (GSK3beta) to regulate cell growth. The expression levels and function of TSC2
      and GSK3beta in hepatocellular carcinoma (HCC) remain unclear. METHODS: The
      protein levels of TSC2 and GSK3beta were measured by immunohistochemistry in
      normal liver (n = 20), HCC (n = 80) and pericancerous tissues (n = 80). The
      correlations between TSC2, and GSK3beta levels, clinicopathological features and
      patient survival were also analyzed. RESULTS: The protein levels of TSC2 and
      GSK3beta in HCC tissues were significantly lower than that in normal liver
      tissues and pericancerous tissues (P < 0.05). Decreased TSC2 and GSK3beta
      expression was found to be significantly correlated with advanced
      clinicopathological characteristics and poor prognosis. The results also showed
      that TSC2 protein levels were associated with GSK3beta expression in HCC
      specimens. CONCLUSION: This is the first demonstration that the decreases in TSC2
      and GSK3beta levels may be associated with vascular invasion, histological grade
      and tumor-node-metastasis classification.

PMID- 24119082
TI  - Poor prognosis of rare sarcomeric gene variants in patients with dilated
      cardiomyopathy.
AB  - BACKGROUND: In dilated cardiomyopathy (DCM), the clinical and prognostic
      implications of rare variants in sarcomeric genes remain poorly understood. To
      address this question, we analyzed the outcome of rare sarcomeric gene variants
      in patients enrolled in our Familial Cardiomyopathy Registry. METHODS: DCM
      families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN
      were identified. Genotype-phenotype association analysis was performed, and long
      term survival-free from death or heart transplant was compared between carriers
      and noncarriers. RESULTS: We found 24 rare variants (3 in MYH6, 3 in MYH7, 3 in
      MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families. The
      phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure
      deaths, 8 heart transplants, 2 ventricular fibrillations). There was no
      difference in the overall long-term survival between carriers and the 33
      noncarriers (p = 0.322). However after 50 years of age, the combined endpoint of
      death or transplant was decreased in carriers as compared to noncarriers (p =
      0.026). CONCLUSIONS: Patients with DCM carrying rare variants in sarcomeric genes
      manifest a poorer prognosis as compared to noncarriers after the age of 50 years.
      These data further support the role of genetic testing in DCM for risk
      stratification.

PMID- 24119084
TI  - Lifestyle change important for patients with hypertension and cardiovascular
      diseases.

PMID- 24119085
TI  - DNA barcoding reveals a largely unknown fauna of Gracillariidae leaf-mining moths
      in the Neotropics.
AB  - Higher taxa often show increasing species richness towards tropical low
      latitudes, a pattern known as the latitudinal biodiversity gradient (LBG). A rare
      reverse LBG (with greater richness towards temperate high latitudes) is exhibited
      by Gracillariidae leaf-mining moths, in which most described species occur in
      northern temperate areas. We carried out the first assessment of gracillariid
      species diversity in two Neotropical regions to test whether the relatively low
      tropical species diversity of this family is genuine or caused by insufficient
      sampling and a strong taxonomic impediment. Field surveys in six French Guianan
      and one Ecuadorian site produced 516 gracillariid specimens that were DNA
      barcoded to facilitate identification and to match larvae inside leaf mines with
      adults. Species delineation from sequence data was approximated using Automatic
      Barcode Gap Discovery and Refined Single Linkage Analysis through the Barcode
      Index Number system, and the proportion of described/undescribed species was
      estimated after comparison with types of 83% of described species. Locally, alpha
      diversity far exceeds that of any known temperate fauna, with as many as 108
      candidate species (59.3% as singletons) collected at one site, and with an
      estimated species richness lower bound of 240 species. Strikingly, at least 85%
      of the species collected as adults were found to be undescribed. Our sampling
      represents the most thorough survey of gracillariid species diversity in the
      Neotropics to date and the results from both our molecular and morphological
      analyses indicate that the current reverse LBG seen in this group is an artefact
      of insufficient sampling and a strong description deficit in the Neotropics. 

PMID- 24119086
TI  - Site-directed mutagenesis of the P225, N230 and H272 residues of succinate
      dehydrogenase subunit B from Botrytis cinerea highlights different roles in
      enzyme activity and inhibitor binding.
AB  - Carboxamide fungicides target succinate dehydrogenase (SDH). Recent field
      monitoring studies have identified Botrytis cinerea isolates resistant to one or
      several SDH inhibitors (SDHIs) with amino acid substitutions in the SDH B
      subunit. We confirmed, by site-directed mutagenesis of the sdhB gene, that each
      of the mutations identified in field strains conferred resistance to boscalid in
      B.cinerea, and in some cases cross-resistance to other SDHIs (fluopyram,
      carboxin). Enzyme inhibition studies showed that the studied modifications
      (SdhB_P225T/L/F, N230I, H272Y/R/L) affected the inhibition of SDH activity by
      SDHIs, directly contributing to resistance. Our results confirm the importance of
      H272, P225 and N230 for carboxamide binding. Modifications of P225 and N230
      conferred resistance to the four carboxamides tested (boscalid, fluopyram,
      carboxin, bixafen). Modifications of H272 had differential effects on the
      susceptibility of SDH to SDHIs. SdhB(H272L) , affected susceptibility to all
      SDHIs, SdhB(H272R) conferred resistance to all SDHIs tested except fluopyram, and
      SdhB(H272Y) conferred fluopyram hypersensitivity. Affinity-binding studies with
      radiolabelled fluopyram revealed strong correlations among the affinity of SDHIs
      for SDH, SDH inhibition and in vivo growth inhibition in the wild type. The
      sdhB(H272Y) mutation did not affect SDH and respiration activities, whereas all
      the other mutations affected respiration by decreasing SDH activity.

PMID- 24119089
TI  - Pulmonary embolism severity index accurately predicts long-term mortality rate in
      patients hospitalized for acute pulmonary embolism.
AB  - BACKGROUND: The Pulmonary Embolism (PE) Severity Index (PESI) is a clinical
      prognostic rule that accurately classifies PE patients into five risk classes
      with increasing mortality. PESI score has been validated in studies with a
      relatively short-term follow-up and its accuracy in predicting long-term
      prognosis has never been established. METHODS: Consecutive patients admitted to
      the tertiary care hospital of Varese (Italy) with an objectively diagnosed PE
      between January 2005 and December 2009 were retrospectively included. Information
      on clinical presentation, diagnostic work-up, risk factors, treatment and
      mortality during a 1-year follow-up was collected. RESULTS: Five hundred and
      thirty-eight patients were enrolled in this study. The mean age was 70.6 years
      (+/- SD 15.2), 44.4% of patients were male, and 27.9% had known cancer. One-year
      follow-up was available for 96.1% of patients. The overall mortality rate was
      23.2% at 3 months, 30.2% at 6 months and 37.1% at 12 months. The discriminatory
      power of the PESI score to predict long-term mortality, expressed as the area
      under the ROC curve, was 0.77 (95%CI, 0.72-0.81) at 3 months, 0.77 (95%CI, 0.73
      0.81) at 6 months and 0.79 (95%CI, 0.75-0.82) at 12 months. The PESI score
      confirmed its accurate prediction in patients without cancer. Simplified PESI had
      a similar overall accuracy to the original PESI at 3 and 6 months, but this was
      significantly lower at 1 year. CONCLUSIONS: The results of this study suggest
      that PESI score may also be an accurate tool to define the 6-month and 1-year
      mortality rates in PE patients.

PMID- 24119087
TI  - Yersinia pseudotuberculosis uses Ail and YadA to circumvent neutrophils by
      directing Yop translocation during lung infection.
AB  - A Yersinia pseudotuberculosis (Yptb) murine model of lung infection was
      previously developed using the serotype III IP2666NdeI strain, which robustly
      colonized lungs but only sporadically disseminated to the spleen and liver. We
      demonstrate here that a serotype Ib Yptb strain, IP32953, colonizes the lungs at
      higher levels and disseminates more efficiently to the spleen and liver compared
      with IP2666NdeI . The role of adhesins was investigated during IP32953 lung
      infection by constructing isogenic Deltaail, Deltainv, DeltapsaE and DeltayadA
      mutants. An IP32953DeltaailDeltayadA mutant initially colonized but failed to
      persist in the lungs and disseminate to the spleen and liver. Yptb expressing
      these adhesins selectively bound to and targeted neutrophils for translocation of
      Yops. This selective targeting was critical for virulence because persistence of
      the DeltaailDeltayadA mutant was restored following intranasal infection of
      neutropenic mice. Furthermore, Ail and YadA prevented killing by complement
      mediated mechanisms during dissemination to and/or growth in the spleen and
      liver, but not in the lungs. Combined, these results demonstratethat Ail and YadA
      are critical, redundant virulence factors during lung infection, because they
      thwart neutrophils by directing Yop-translocation specifically into these cells. 

PMID- 24119088
TI  - Effectiveness of first-line antiretroviral therapy and correlates of longitudinal
      changes in CD4 and viral load among HIV-infected children in Ghana.
AB  - BACKGROUND: Antiretroviral therapy (ART) scale-up in resource-limited countries,
      with limited capacity for CD4 and HIV viral load monitoring, presents a unique
      challenge. We determined the effectiveness of first-line ART in a real world
      pediatric HIV clinic and explored associations between readily obtainable patient
      data and the trajectories of change in CD4 count and HIV viral load. METHODS: We
      performed a longitudinal study of a cohort of HIV-infected children initiating
      ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged
      0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6
      months and genotypic resistance testing was performed for children failing
      therapy. A mixed linear modeling approach, combining fixed and random subject
      effects, was employed for data analysis. RESULTS: Ninety HIV-infected children
      aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line
      regimen among study participants was 83.3%, based on WHO criteria for virologic
      failure. Fifteen of the 90 (16.7%) children met the criteria for virologic
      treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic
      failures harbored viruses with  >= 1 drug resistant mutations (DRMs); M184V/K103N
      was the predominant resistance pathway. Age at initiation of therapy, child's
      gender, having a parent as a primary care giver, severity of illness, and type of
      regimen were associated with treatment outcomes. CONCLUSIONS: First-line ART
      regimens were effective and well tolerated. We identified predictors of the
      trajectories of change in CD4 and viral load to inform targeted laboratory
      monitoring of ART among HIV-infected children in resource-limited countries.

PMID- 24119090
TI  - Effectiveness of novel 5-(5-amino-1-aryl-1H-pyrazol-4-yl)-1H-tetrazole
      derivatives against promastigotes and amastigotes of Leishmania amazonensis.
AB  - In this research, a series of substituted 5-(5-amino-1-aryl-1H-pyrazol-4-yl)-1H
      tetrazoles were synthesized and evaluated for in vitro antileishmanial activity.
      Among the derivatives, examined compounds 3b and 3l exhibited promising activity
      against promastigotes and amastigotes forms of Leishmania amazonensis. The
      cytotoxicity of these compounds was evaluated on murine cells, giving access to
      the corresponding selectivity index (SI). 

PMID- 24119091
TI  - Genetic diversity and population structure of Lantana camara in India indicates
      multiple introductions and gene flow.
AB  - Lantana camara is a highly invasive plant, which has spread over 60 countries and
      island groups of Asia, Africa and Australia. In India, it was introduced in the
      early nineteenth century, since when it has expanded and gradually established
      itself in almost every available ecosystem. We investigated the genetic diversity
      and population structure of this plant in India in order to understand its
      introduction, subsequent range expansion and gene flow. A total of 179
      individuals were sequenced at three chloroplast loci and 218 individuals were
      genotyped for six nuclear microsatellites. Both chloroplasts (nine haplotypes)
      and microsatellites (83 alleles) showed high genetic diversity. Besides, each
      type of marker confirmed the presence of private polymorphism. We uncovered low
      to medium population structure in both markers, and found a faint signal of
      isolation by distance with microsatellites. Bayesian clustering analyses revealed
      multiple divergent genetic clusters. Taken together, these findings (i.e. high
      genetic diversity with private alleles and multiple genetic clusters) suggest
      that Lantana was introduced multiple times and gradually underwent spatial
      expansion with recurrent gene flow.

PMID- 24119092
TI  - Platelet increases survival in a model of 90% hepatectomy in rats.
AB  - BACKGROUND & AIMS: Ninety per cent hepatectomy in rodents is a model for acute
      liver failure. It has been reported that platelets have a strong effect enhancing
      liver regeneration, because of the production of several growth factors such as
      serotonin. The aim of this study was to investigate the role of microencapsulated
      platelets on 90% hepatectomy in rats. METHODS: Platelets (PLT) were
      microencapsulated in sodium alginate and implanted in the peritoneum of rats
      after 90% partial hepatectomy (PH). Control group received empty capsules (EC).
      Animals were euthanized at 6, 12, 24, 48 and 72 h post PH (n=9-12/group/time) to
      evaluate liver regeneration rate, mitotic index, liver content, serum and tissue
      levels of Interleukin 6 (IL-6) and serotonin and its receptor 5-hydroxytryptamine
      type 2B (5Ht2b). Survival rate in 10 days was evaluated in a different set of
      animals (n=20/group). RESULTS: Platelets group showed the highest survival rate
      despite the lowest liver regeneration rate at any time point. Mitotic and BrdU
      index showed no difference between groups. However, the number of hepatocytes was
      higher and the internuclear distance was shorter for PLT group. Liver dry weight
      was similar in both groups indicating that water was the main responsible factor
      for the weight difference. Gene expression of IL-6 in the liver was significantly
      higher in EC group 6 h after PH, whereas 5Ht2b was up-regulated at 72 h in PLT
      group. CONCLUSIONS: Platelets enhance survival of animals with 90% PH, probably
      by an early protective effect on hepatocytes and the increase in growth factor
      receptors.

PMID- 24119095
TI  - Aztreonam for febrile neutropenia in patients with beta-lactam allergy.
AB  - BACKGROUND: Beta-lactam antibiotics are the mainstay of empiric therapy for
      febrile neutropenia. Aztreonam may benefit certain patients because of a lack of
      cross-hypersensitivity to penicillins and cephalosporins. This is the first
      study, to our knowledge, to evaluate the efficacy of aztreonam as monotherapy for
      febrile neutropenia (FN). METHODS: Our study was a single-center retrospective
      chart review of patients >=18 years of age receiving aztreonam for the treatment
      of FN. Primary outcome was treatment success of aztreonam monotherapy. Secondary
      analyses included need for modification to antimicrobial therapy, patients
      transitioned to aztreonam from another empiric regimen, and patients receiving
      aztreonam in combination with other antibacterial agents. RESULTS: In patients
      prescribed aztreonam for first fever, 11 of 27 (40.7%) patients who received
      aztreonam alone and 19 of 40 (47.5%) given aztreonam plus another antibiotic
      responded within 96 h (P = 0.62). Twenty-four (89%) patients prescribed aztreonam
      monotherapy were alive when FN resolved or treatment ended. Infectious mortality
      was low (1 patient, 3.7%). In patients prescribed aztreonam monotherapy following
      an adverse reaction to cefepime, 6 of 11 (54.5%) responded within 96 h of
      initiating aztreonam; 10 (91%) were alive when FN resolved or treatment ended.
      CONCLUSION: Aztreonam monotherapy may be acceptable for use in patients with a
      history of beta-lactam hypersensitivity or following an adverse reaction with
      another beta-lactam. Further studies are needed to compare efficacy of aztreonam
      monotherapy with other therapies for the treatment of FN.

PMID- 24119093
TI  - Yeast replicative aging: a paradigm for defining conserved longevity
      interventions.
AB  - The finite replicative life span of budding yeast mother cells was demonstrated
      as early as 1959, but the idea that budding yeast could be used to model aging of
      multicellular eukaryotes did not enter the scientific mainstream until relatively
      recently. Despite continued skepticism by some, there are now abundant data that
      several interventions capable of extending yeast replicative life span have a
      similar effect in multicellular eukaryotes including nematode worms, fruit flies,
      and rodents. In particular, dietary restriction, mTOR signaling, and sirtuins are
      among the most studied longevity interventions in the field. Here, we describe
      key conserved longevity pathways in yeast and discuss relationships that may help
      explain how such broad conservation of aging processes could have evolved. 

PMID- 24119096
TI  - Pyogenic liver abscess trends in South Australia.
AB  - BACKGROUND: Pyogenic liver abscess (PLA) is an uncommon but potentially life
      threatening condition. Due to advances in diagnostic and treatment methods, the
      mortality rate has reduced in recent decades. The aim of this study was to gather
      recent data to examine PLA trends in South Australia. METHODS: The medical
      records of all patients admitted to The Queen Elizabeth Hospital, South
      Australia, between November 2000 and November 2009 with a primary or secondary
      diagnosis of PLA were retrospectively reviewed. RESULTS: Thirty-six patients were
      identified. Twenty (55.6%) were male and 16 (44.4%) female. The mean patient age
      was 70.2 years. A single PLA was found in 21 (58.3%) patients and multiple
      abscesses in 15 (41.7%) patients. Segment 7 of the liver was most commonly
      affected (10 cases). In 12 patients, multiple organisms were identified.
      Escherichia coli, Klebsiella pneumonia and Streptococcus species were most
      commonly identified. All patients received antibiotics and 27 (75%) received
      additional treatment. Nine patients received open abscess drainage. Fourteen
      received ultrasound-guided or computed tomography-guided percutaneous drainage or
      aspiration. One patient died as a direct result of a PLA. DISCUSSION: Since its
      first description, the epidemiology of PLA has changed. Patients diagnosed with
      PLA are now older, the male predominance is less and the organism more likely to
      originate from the biliary tract. The approach to PLA has also progressed with
      more accurate imaging and better treatment methods becoming available, which has
      resulted in a low mortality rate. This series confirms the described trends in
      South Australia.

PMID- 24119097
TI  - Comparison of a new portable digital meniscometer and optical coherence
      tomography in tear meniscus radius measurement.
AB  - PURPOSE: Non-invasive measurement of tear meniscus radius (TMR) is useful in the
      assessment of tear volume for dry eye diagnosis. This study investigates the
      agreement between a new, portable, slit-lamp mounted, digital meniscometer (PDM)
      and optical coherence tomography (OCT) in the measurement of human TMR. METHODS:
      Images of the tear meniscus at the centre of the lower lid of 30 normal subjects
      (8M, 22F; mean age 27.5 SD +/- 9.6 years) were taken using the PDM and the OCT.
      On the PDM and OCT images, TMR was measured using imagej 1.46b software. The
      meniscus on the OCT images was subdivided vertically into three equal sections
      and the radius calculated for each: bottom (BTMR), centre (CTMR) and top (TTMR).
      The relationship between PDM and OCT measurements was analysed using Spearman's
      rank coefficient, and differences between PDM and OCT subsection measurements
      were evaluated using Bland-Altman plots. RESULTS: Tear meniscus radius measured
      with the PDM (0.25 +/- 0.06 mm) and OCT (0.29 +/- 0.09 mm) was significantly
      correlated (r = 0.675; p < 0.001). The mean differences between TMR using the PDM
      and the subsections from OCT showed that TMR measured with PDM was greater for
      BTMR (0.07 mm; CI 0.05-0.10; p < 0.001), similar for CTMR (-0.01 mm; CI -0.04 to
      0.02; p = 0.636) and steeper for TTMR (-0.07 mm; CI -0.10 to -0.04; p < 0.001).
      CONCLUSIONS: Portable digital meniscometer and OCT measurements of the TMR are
      significantly correlated, suggesting that the new PDM is a useful surrogate for
      OCT in this respect. The PDM appears to measure the radius of the central section
      of the tear meniscus.

PMID- 24119094
TI  - Integrating microRNA and mRNA expression profiling in Symbiodinium
      microadriaticum, a dinoflagellate symbiont of reef-building corals.
AB  - BACKGROUND: Animal and plant genomes produce numerous small RNAs (smRNAs) that
      regulate gene expression post-transcriptionally affecting metabolism,
      development, and epigenetic inheritance. In order to characterize the repertoire
      of endogenous smRNAs and potential gene targets in dinoflagellates, we conducted
      smRNA and mRNA expression profiling over 9 experimental treatments of cultures
      from Symbiodinium microadriaticum, a photosynthetic symbiont of scleractinian
      corals. RESULTS: We identified a set of 21 novel smRNAs that share stringent key
      features with functional microRNAs from other model organisms. smRNAs were
      predicted independently over all 9 treatments and their putative gene targets
      were identified. We found 1,720 animal-like target sites in the 3'UTRs of 12,858
      mRNAs and 19 plant-like target sites in 51,917 genes. We assembled a
      transcriptome of 58,649 genes and determined differentially expressed genes
      (DEGs) between treatments. Heat stress was found to produce a much larger number
      of DEGs than other treatments that yielded only few DEGs. Analysis of DEGs also
      revealed that minicircle-encoded photosynthesis proteins seem to be common
      targets of transcriptional regulation. Furthermore, we identified the core RNAi
      protein machinery in Symbiodinium. CONCLUSIONS: Integration of smRNA and mRNA
      expression profiling identified a variety of processes that could be under
      microRNA control, e.g. protein modification, signaling, gene expression, and
      response to DNA damage. Given that Symbiodinium seems to have a paucity of
      transcription factors and differentially expressed genes, identification and
      characterization of its smRNA repertoire establishes the possibility of a range
      of gene regulatory mechanisms in dinoflagellates acting post-transcriptionally.

PMID- 24119098
TI  - Medical management of Alternaria keratitis with endophthalmitis in a patient with
      a corneal graft.

PMID- 24119099
TI  - Adult onset Still's disease with persistent skin lesions complicated by secondary
      hemophagocytic lymphohistiocytosis.

PMID- 24119100
TI  - Characterization of thermophilic bacilli from a milk powder processing plant.
AB  - AIMS: To determine whether strains of Geobacillus stearothermophilus isolated
      from a milk powder manufacturing plant were different in their ability to form
      biofilms and produce spores. In addition, this study evaluated whether there were
      other physiological characteristics that could differentiate these strains.
      METHODS AND RESULTS: Ten G. stearothermophilus strains and one Anoxybacillus
      species were isolated from a milk powder manufacturing plant. A microtitre plate
      assay was used to show that these strains differed in their abilities to form
      biofilms and produce spores. Scanning electron microscopy showed differences in
      the biofilm morphologies of three of the G. stearothermophilus strains.
      Biochemical profiling, matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry and fatty acid profiling further showed that they had distinct
      characteristics. CONCLUSIONS: These G. stearothermophilus strains, isolated from
      the same environment, showed differences in their ability to form biofilms and
      produce endospores. Based on the multiple characterization methods used in this
      study, these strains of G. stearothermophilus isolated from one manufacturing
      plant are diverse. SIGNIFICANCE AND IMPACT OF THE STUDY: Differences in the
      ability of G. stearothermophilus to form biofilms and produce spores may
      influence the cleaning method used to control the growth of thermophilic bacilli
      in a dairy processing environment.

PMID- 24119101
TI  - Treatment of LUTS secondary to BPH while preserving sexual function: randomized
      controlled study of prostatic urethral lift.
AB  - INTRODUCTION: We analyzed data obtained from a randomized controlled blinded
      study of the prostatic urethral lift (PUL) to evaluate the sexual side effects of
      this novel treatment. AIMS: We sought to determine whether PUL, when conducted in
      a randomized study, significantly improved lower urinary tract symptoms (LUTS)
      and urinary flow rate while preserving sexual function. METHODS: Men >=50 years
      with prostates 30-80 cc, International Prostate Symptom Score (IPSS) >12, and
      peak urinary flow rate (Qmax) <=12 ml/s were randomized 2:1 between PUL and sham.
      Sexual activity was not an inclusion criterion. In PUL, permanent transprostatic
      implants are placed to retract encroaching lateral lobes and open the prostatic
      fossa. Sham entailed rigid cystoscopy with sounds to mimic PUL and a blinding
      screen. MAIN OUTCOME MEASURES: Blinded groups were compared at 3 months and
      active arm then followed to 12 months for LUTS with IPSS and for sexual function
      with sexual health inventory for men (SHIM) and Male Sexual Health Questionnaire
      for Ejaculatory Dysfunction (MSHQ-EjD). Subjects were censored from primary
      sexual function analysis if they had baseline SHIM < 5 at enrollment. Secondary
      stratified analysis by erectile dysfunction (ED) severity was conducted. RESULTS:
      There was no evidence of degradation in erectile or ejaculatory function after
      PUL. SHIM and MSHQ-EjD scores were not different from control at 3 months but
      were modestly improved and statistically different from baseline at 1 year.
      Ejaculatory bother score was most improved with a 40% improvement over baseline.
      Twelve-month SHIM was significantly improved from baseline for men entering the
      study with severe ED, P = 0.016. IPSS and Qmax were significantly superior to
      both control at 3 months and baseline at 1 year. There was no instance of de novo
      sustained anejaculation or ED over the course of the study. CONCLUSIONS: The PUL
      improves LUTS and urinary flow while preserving erectile and ejaculatory
      function.

PMID- 24119102
TI  - The dilemma of post-ureteroscopy stenting.

PMID- 24119103
TI  - Closure of fistula-in-ano with laser--FiLaCTM: an effective novel sphincter
      saving procedure for complex disease.
AB  - AIM: Fistula laser closure (FiLaCTM) is a novel sphincter-saving procedure for
      the treatment of anal fistula. Primary closure of the track is achieved using
      laser energy emitted by a radial fibre connected to a diode laser. The energy
      causes shrinkage of the tissue around the radial fibre with the aim being to
      close the track. This pilot study was designed to investigate the safety and
      effectiveness of this new technique in the treatment of anal fistula. METHOD:
      Thirty-five patients with anal fistula underwent the FiLaCTM procedure. They had
      either a primary or a recurrent trans-sphincteric anal fistula, a previously
      placed seton or a fistula involving a significant portion of the sphincter with a
      potential risk of postoperative incontinence on fistulotomy. The surgical
      procedure consisted of 'sealing' the fistula by laser energy. The primary end
      point was cure of the disease and evaluation of morbidity. The secondary end
      point was an assessment of the degree of postoperative continence using the
      Cleveland Clinic Florida (CCF) Fecal Incontinence Score. RESULTS: The median
      operation time was 20 (6-35) min. No intra-operative complications were reported.
      Median duration of follow up was 20 (3-36) months. Primary healing was observed
      in 25 (71.4%) patients. There were eight (23%) failures and two recurrences at 3
      and 6 months after the operation. No patient reported incontinence
      postoperatively. CONCLUSION: The laser FiLaCTM procedure for fistula-in-ano is a
      safe, relatively simple, minimally invasive, sphincter-saving procedure with a
      high chance of success.

PMID- 24119104
TI  - Physiology and analysis of the electrocardiographic T wave in mice.
AB  - AIM: The murine electrocardiogram (ECG) is a valuable tool in cardiac research,
      although the definition of the T wave has been a matter of debate for several
      years potentially leading to incomparable data. By this study, we seek to make a
      clear definition of the murine T wave. Moreover, we investigate the consequences
      of performing QT interval correction in anaesthetized mice. METHODS:
      Electrocardiograms from conscious mice were recorded by implanted telemetry
      devices. Surface ECGs were recorded from anaesthetized mice before and during
      pharmacological interventions, ventricular ischaemia and heart failure. Right
      atrial pacing was performed to evaluate the relationship between heart rate and
      QT intervals. RESULTS: Electrocardiogram traces of conscious and anaesthetized
      mice (lead II) showed separable positive J waves and negative T waves. The end of
      the T wave was determined as the point where the T wave returned to the
      isoelectric line. Atrial pacing revealed that the duration of the QT interval is
      independent of heart rate in anaesthetized mice. The calcium channel blocker,
      verapamil, prolonged the PR interval; however, the polarities of the J and T
      waves were not changed. Local cardiac ischaemia and beta-adrenergic stimulation
      caused indistinguishable positive J and T waves. In contrast, chronic heart
      failure caused entirely negative J and T waves. In every case, the end of the T
      wave was clearly distinguishable on the ECG. CONCLUSION: The end of the T wave is
      readily available from conscious and anaesthetized mice. Heart rate correction of
      QT interval duration in the anaesthetized mouse is not recommended.

PMID- 24119105
TI  - Mucociliary clearance: pathophysiological aspects.
AB  - Mucociliary clearance has long been known to be a significant innate defence
      mechanism against inhaled microbes and irritants. Important knowledge has been
      gathered regarding the anatomy and physiology of this system, and in recent
      years, extensive studies of the pathophysiology related to lung diseases
      characterized by defective mucus clearance have resulted in a variety of
      therapies, which might be able to enhance clearance from the lungs. In addition,
      ways to study in vivo mucociliary clearance in humans have been developed. This
      can be used as a means to assess the effect of different pharmacological
      interventions on clearance rate, to study the importance of defective mucus
      clearance in different lung diseases or as a diagnostic tool in the work-up of
      patients with recurrent airway diseases. The aim of this review is to provide an
      overview of the anatomy, physiology, pathophysiology, and clinical aspects of
      mucociliary clearance and to present a clinically applicable test that can be
      used for in vivo assessment of mucociliary clearance in patients. In addition,
      the reader will be presented with a protocol for this test, which has been
      validated and used as a diagnostic routine tool in the work-up of patients
      suspected for primary ciliary dyskinesia at Rigshospitalet, Denmark for over a
      decade. 

PMID- 24119106
TI  - Application of nontargeted metabolite profiling to discover novel markers of
      quality traits in an advanced population of malting barley.
AB  - The process of breeding superior varieties for the agricultural industry is
      lengthy and expensive. Plant metabolites may act as markers of quality traits,
      potentially expediting the appraisal of experimental lines during breeding. Here,
      we evaluated the utility of metabolites as markers by assessing metabolic
      variation influenced by genetic and environmental factors in an advanced breeding
      setting and in relation to the phenotypic distribution of 20 quality traits.
      Nontargeted liquid chromatography-mass spectrometry metabolite profiling was
      performed on barley (Hordeum vulgare L.) grain and malt from 72 advanced malting
      barley lines grown at two distinct but climatically similar locations, with 2-row
      and 6-row barley as the main genetic factors. 27 420 molecular features were
      detected, and the metabolite and quality trait profiles were similarly influenced
      by genotype and environment; however, malt was more influenced by genotype
      compared with barley. An O2PLS model characterized molecular features and quality
      traits that covaried, and 1319 features associated with at least one of 20
      quality traits. An indiscriminant MS/MS acquisition and novel data analysis
      method facilitated the identification of metabolites. The analysis described 216
      primary and secondary metabolites that correlated with multiple quality traits
      and included amines, amino acids, alkaloids, polyphenolics and lipids. The
      mechanisms governing quality trait-metabolite associations were interpreted based
      on colocalization to genetic markers and their gene annotations. The results of
      this study support the hypothesis that metabolism and quality traits are co
      influenced by relatively narrow genetic and environmental factors and illustrate
      the utility of grain metabolites as functional markers of quality traits.

PMID- 24119107
TI  - Cytokine profiling in patients with VCP-associated disease.
AB  - Valosin containing protein (VCP) disease (also known as Inclusion Body Myopathy,
      Paget Disease of Bone and Frontotemporal Dementia [IBMPFD] syndrome) is caused by
      mutations in the gene encoding VCP classically affecting the muscle, bone and
      brain. Although the genetic cause has been identified, details regarding the
      pathogenesis of IBMPFD have not been fully determined. Muscle wasting observed in
      VCP disease is suggestive of cytokine imbalance. We hypothesized that
      dysfunctional protein homeostasis caused by VCP mutations leads to cytokine
      imbalances thereby contributing to the muscle wasting phenotype. Circulating
      levels of interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha
      (TNF a) and epidermal growth factor (EGF) were measured in plasma of patients
      with VCP disease or controls. TNF a and EGF were significantly altered in VCP
      disease as compared to control. TNF a was up-regulated, consistent with a
      cachexia phenotype and EGF levels were increased. No significant differences were
      observed in IL-4 and IL-6. Cytokine imbalances may be associated with VCP disease
      and may play a contributory role in VCP myopathy. Further understanding of how
      VCP dysfunction leads to aberrant protein homeostasis and subsequent cytokine
      imbalances may also aid in the understanding of other proteinopathies and in the
      development of novel treatments. 

PMID- 24119108
TI  - Share with women. Caring for your perineum after you give birth.

PMID- 24119109
TI  - Microarray diagnosis of antibody-mediated rejection in kidney transplant
      biopsies: an international prospective study (INTERCOM).
AB  - In a reference set of 403 kidney transplant biopsies, we recently developed a
      microarray-based test that diagnoses antibody-mediated rejection (ABMR) by
      assigning an ABMR score. To validate the ABMR score and assess its potential
      impact on practice, we performed the present prospective INTERCOM study
      (clinicaltrials.gov NCT01299168) in 300 new biopsies (264 patients) from six
      centers: Baltimore, Barcelona, Edmonton, Hannover, Manchester and Minneapolis. We
      assigned ABMR scores using the classifier created in the reference set and
      compared it to conventional assessment as documented in the pathology reports.
      INTERCOM documented uncertainty in conventional assessment: In 41% of biopsies
      where ABMR features were noted, the recorded diagnoses did not mention ABMR. The
      ABMR score correlated with ABMR histologic lesions and donor-specific antibodies,
      but not with T cell-mediated rejection lesions. The agreement between ABMR scores
      and conventional assessment was identical to that in the reference set (accuracy
      85%). The ABMR score was more strongly associated with failure than conventional
      assessment, and when the ABMR score and conventional assessment disagreed, only
      the ABMR score was associated with early progression to failure. INTERCOM
      confirms the need to reduce uncertainty in the diagnosis of ABMR, and
      demonstrates the potential of the ABMR score to impact practice. 

PMID- 24119110
TI  - Adjuvant epoetin-beta with peginterferon-alpha and ribavirin in Japanese
      ribavirin-intolerant relapsed patients with chronic hepatitis C genotype 2.
AB  - Erythropoietin is widely used in the USA and some other Western countries to
      maintain doses of ribavirin during peginterferon/ribavirin-based treatment for
      chronic hepatitis C virus (HCV) infection. However, the impact of erythropoietin
      on sustained virological response (SVR) is unclear. Here, we report the cases of
      three Japanese ribavirin-intolerant relapsed patients with HCV genotype 2 who
      achieved SVR from retreatment by adding erythropoietin. Three women aged 50, 64
      and 68 years with chronic HCV genotype 2 received retreatment with peginterferon
      alpha and ribavirin. During their prior therapy, HCV RNA became negative
      according to real-time polymerase chain reaction at weeks 4-8 in all three
      patients; however, the total dose of ribavirin was 18.1-30.6% lower than the
      planned dose, and HCV RNA relapsed post-treatment. At present, epoetin-beta 24
      000 IU was introduced at weeks 2 or 3 of dual-combination therapy, resulting in a
      less than 4.2% reduction in the total dose of ribavirin. HCV RNA became negative
      at weeks 4-8, and all patients achieved SVR. Until the next-generation antiviral
      treatments for HCV genotype 2 become available, the addition of erythropoietin to
      dual therapy can be a treatment of choice for ribavirin-intolerant relapsed
      patients. 

PMID- 24119112
TI  - Comparison of efficacy and safety between bisoprolol transdermal patch (TY-0201)
      and bisoprolol fumarate oral formulation in Japanese patients with grade I or II
      essential hypertension: randomized, double-blind, placebo-controlled study.
AB  - TY-0201 (TY) is a new drug absorbed by the transdermal delivery system developed
      for the treatment of hypertension, which contains the free base of bisoprolol
      fumarate that is widely used. An 8-week randomized, double-blind, placebo
      controlled study was conducted in hypertensive patients to evaluate the
      superiority of TY 8 mg to placebo and the noninferiority of TY 8 mg to bisoprolol
      fumarate oral formulation (BO) 5 mg. Changes in diastolic blood pressure (BP)
      (primary endpoint) from baseline in the TY 8 mg group, the BO 5 mg group, and the
      placebo group were -12.2 mm Hg, -11.8 mm Hg, and -3.7 mm Hg, respectively, with
      TY 8 mg demonstrating superiority to placebo and noninferiority to BO 5 mg.
      Changes from baseline for systolic BP and pulse rate produced significant
      reductions compared with placebo. TY is expected to serve as a new treatment
      approach for hypertensive patients. 

PMID- 24119113
TI  - Development of genomic resources for the tick Ixodes ricinus: isolation and
      characterization of single nucleotide polymorphisms.
AB  - Assessing the genetic variability of the tick Ixodes ricinus-an important vector
      of pathogens in Europe-is an essential step for setting up antitick control
      methods. Here, we report the first identification of a set of SNPs isolated from
      the genome of I. ricinus, by applying a reduction in genomic complexity,
      pyrosequencing and new bioinformatics tools. Almost 1.4 million of reads (average
      length: 528 nt) were generated with a full Roche 454 GS FLX run on two reduced
      representation libraries of I. ricinus. A newly developed bioinformatics tool
      (DiscoSnp), which isolates SNPs without requiring any reference genome, was used
      to obtain 321 088 putative SNPs. Stringent selection criteria were applied in a
      bioinformatics pipeline to select 1768 SNPs for the development of specific
      primers. Among 384 randomly SNPs tested by Fluidigm genotyping technology on 464
      individuals ticks, 368 SNPs loci (96%) exhibited the presence of the two expected
      alleles. Hardy-Weinberg equilibrium tests conducted on six natural populations of
      ticks have shown that from 26 to 46 of the 384 loci exhibited significant
      heterozygote deficiency. 

PMID- 24119111
TI  - Lipids and cell death in yeast.
AB  - Understanding lipid-induced malfunction represents a major challenge of today's
      biomedical research. The connection of lipids to cellular and organ dysfunction,
      cell death, and disease (often referred to as lipotoxicity) is more complex than
      the sole lipotoxic effects of excess free fatty acids and requires genetically
      tractable model systems for mechanistic investigation. We herein summarize recent
      advances in the field of lipid-induced toxicity that employ the established model
      system for cell death and aging research of budding yeast Saccharomyces
      cerevisiae. Studies in yeast have shed light on various aspects of lipotoxicity,
      including free fatty acid toxicity, sphingolipid-modulated cell death as well as
      the involvement of cardiolipin and lipid peroxidation in the mitochondrial
      pathways of apoptosis. Regimens used range from exogenously applied lipids,
      genetic modulation of lipolysis and triacylglyceride synthesis, variations in
      sphingolipid/ceramide metabolism as well as changes in peroxisome function by
      either genetic or pharmacological means. In future, the yeast model of programmed
      cell death will further contribute to the clarification of crucial questions of
      lipid-associated malfunction. 

PMID- 24119115
TI  - Potassium channels: structures, diseases, and modulators.
AB  - Potassium channels participate in many critical biological functions and play
      important roles in a variety of diseases. In recent years, many significant
      discoveries have been made which motivate us to review these achievements. The
      focus of our review is mainly on three aspects. Firstly, we try to summarize the
      latest developments in structure determinants and regulation mechanism of all
      types of potassium channels. Secondly, we review some diseases induced by or
      related to these channels. Thirdly, both qualitative and quantitative approaches
      are utilized to analyze structural features of modulators of potassium channels.
      Our analyses further prove that modulators possess some certain natural-product
      scaffolds. And pharmacokinetic parameters are important properties for organic
      molecules. Besides, with in silico methods, some features that can be used to
      differentiate modulators are derived. There is no doubt that all these studies on
      potassium channels as possible pharmaceutical targets will facilitate future
      translational research. All the strategies developed in this review could be
      extended to studies on other ion channels and proteins as well. 

PMID- 24119114
TI  - SOD2 gene Val16Ala polymorphism is associated with macroalbuminuria in Mexican
      type 2 diabetes patients: a comparative study and meta-analysis.
AB  - BACKGROUND: Several studies in type 2 diabetes patients have shown significant
      associations between the SOD2 gene Val16Ala polymorphism and albuminuria, but
      this association has not been explored in the Mexican population. METHODS: We
      evaluated the association between the SOD2 gene Val16Ala polymorphism (rs4880)
      and macroalbuminuria in a sample of 994 unrelated Mexican type 2 diabetes
      patients. The study included 119 subjects with urinary albumin >300 mg/dL and 875
      subjects with urinary albumin <= 30 mg/dL. Genotyping of the SOD2 gene Val16Ala
      SNP was carried out with Real-Time Polymerase Chain Reaction (RT-PCR). RESULTS:
      The frequency of the TT genotype was 6.7% higher in participants with
      macroalbuminuria than in the normoalbuminuria group (16.8% vs. 10.1%). Using a
      logistic regression analysis, we observed that individuals with the CC genotype
      had significantly lower risks of macroalbuminuria than those with the TT genotype
      (OR=0.42, p=0.034). We carried out a meta-analysis combining our data with data
      from four previous studies and estimated an odds ratio (95% CI) for the C allele
      (with respect to the reference T allele) of 0.65 (0.52-0.80, p<0.001).
      CONCLUSIONS: A significant association was found between the SOD2 Val16Ala
      polymorphism and macroalbuminuria in a sample of Mexican type 2 diabetes
      patients.

PMID- 24119116
TI  - [Individualized drug compounding].

PMID- 24119119
TI  - Magistral formulations and pruritus therapy - What is established, what is
      confirmed, what is new?
AB  - Pruritus is a common symptom encountered by many different specialties. One must
      clinically differentiate between pruritus associated with skin disease or
      inflammation and pruritus with normal skin. Searching for possible underlying
      diseases is indispensable, because pruritus can be very chronic and has multiple
      pathogenetic mechanisms. Therapy - especially topical therapy - is difficult and
      often not successful. Very often systemic treatment has to be combined with
      topical approaches, considering both the active ingredients and appropriate
      vehicles. There are still open therapeutic gaps in the pharmaceutical product
      market, which can partially be resolved by using standard prescriptions for
      formulations. Due to the new pharmacy practice order, standardized compounded
      formulations should be given preference, since individual formulations often do
      not pass the plausibility check of the compounding pharmacist. Also the use of
      cosmetic ingredients (by example, commercial cold creams) is no longer permitted,
      since only ingredients with pharmaceutical quality can be used in compounding. We
      will show - based on practical cases - different therapeutic options for
      treatment with standardized magistral formulations from the NRF (New German
      Pharmacopoeia for compounded medications).

PMID- 24119121
TI  - A 36-week retrospective open trial comparing the efficacy of biological therapies
      in nail psoriasis.
AB  - BACKGROUND: Nail psoriasis occurs in about 50% of psoriatic patients and can be
      psychologically devastating since it appears on visible areas. Up to now there is
      no evidence about what biological drugs is the most effective on nail psoriasis.
      OBJECTIVES: The aim of our study was to determine if one of the four biological
      drugs approved in our country (infliximab, adalimumab, etanercept, ustekinumab)
      is more effective than the others for nail psoriasis. MATERIALS AND METHODS: A
      single-center, retrospective study was conducted to assess the efficacy of
      biological therapies in patients with moderate to severe psoriasis with nail
      involvement. NAPSI was evaluated in all psoriatic patients. Kruskal-Wallis and
      Fisher's exact tests were used to analyze the data. RESULTS: A global
      statistically significant improvement in mean NAPSI from baseline to 12, 24 and
      36 weeks was observed in all patients. At 12 weeks 27.78% of the patients reach
      NAPSI 75, at 24 weeks 81.48% and at 36 weeks 88.89%. The improvement in nail
      psoriasis is not significantly different between groups. An improvement in the
      mean Psoriasis Area and Severity Index score was also achieved CONCLUSIONS:
      Biological therapies have shown to ameliorate psoriatic nail lesions. We did not
      find any statistically significant differences between the four biological drugs
      investigated.

PMID- 24119127
TI  - [Daily Notes. Alleviating distressing skin condition in more than one million
      Kenyan school children -- a non-profit organization celebrating its 20th
      anniversary].

PMID- 24119130
TI  - Evaluation of the effect of a comprehensive multidisciplinary care pathway for
      hip fractures: design of a controlled study.
AB  - BACKGROUND: Hip fractures constitute an economic burden on healthcare resources.
      Most persons with a hip fracture undergo surgery. As morbidity and mortality
      rates are high, perioperative care leaves room for improvement. Improvement can
      be achieved if it is organized in comprehensive care pathways, but the
      effectiveness of these pathways is not yet clear. Hence the objective of this
      study is to compare the clinical effectiveness of a comprehensive care pathway
      with care as usual on self-reported limitations in Activities of Daily Living.
      METHODS/DESIGN: A controlled trial will be conducted in which the comprehensive
      care pathway of University Medical Center Groningen will be compared with care as
      usual in two other, nonacademic, hospitals. In this trial, propensity scores will
      be used to adjust for differences at baseline between the intervention and
      control group. Propensity scores can be used in intervention studies where a
      classical randomized controlled trial is not feasible. Patients aged 60 years and
      older will be included. The hypothesis is that 15% more patients at University
      Medical Center Groningen compared with patients in the care-as-usual condition
      will have recovered at least as well at 6 months follow-up to pre-fracture levels
      for Activities of Daily Living. DISCUSSION: This study will yield new knowledge
      with respect to the clinical effectiveness of a comprehensive care pathway for
      the treatment of hip fractures. This is relevant because of the growing incidence
      of hip fractures and the consequent massive burden on the healthcare system.
      Additionally, this study will contribute to the growing knowledge of the
      application of propensity scores, a relatively novel statistical technique to
      simulate a randomized controlled trial in studies where it is not possible or
      difficult to execute this kind of design. TRIAL REGISTRATION: Nederlands Trial
      Register NTR3171.

PMID- 24119132
TI  - The performance of standardized patients in portraying clinical scenarios in
      speech-language therapy.
AB  - BACKGROUND: Standardized patients (SPs) are frequently included in the clinical
      preparation of students in the health sciences. An acknowledged benefit of using
      SPs is the opportunity to provide a standardized method by which students can
      demonstrate and develop their competency. Relatively little is known, however,
      about the capacity of SPs to offer an accurate and standardized performance
      across a speech-language therapy student cohort. AIMS: To investigate the
      accuracy, reproducibility (consistent performance of each SP across student
      interviews) and replicability (consistent performance of a number of SPs across
      each scenario) of SPs portraying three scenarios, each as a parent of a child
      presenting with a speech disorder. METHODS & PROCEDURES: Forty-four speech
      language therapy students interviewed four SPs to gain a case history. All
      interviews were videotaped. The accuracy of SP portrayal of key features of each
      scenario was scored by an expert rater and two other raters. Data were analysed
      to determine levels of accuracy, reproducibility and replicability, and inter
      rater reliability was evaluated. OUTCOMES & RESULTS: SPs were found to have
      moderate to high levels of accuracy across the three scenarios. There were no
      significant differences in the performances of each individual SP across
      interviews or between all SPs on each scenario, indicating that reproducibility
      and replicability were achieved. Overall inter-rater reliability between raters
      across all scenarios was greater than 80%. CONCLUSIONS & IMPLICATIONS: The
      results would seem to indicate that SPs can present in a standardized manner
      within a speech-language therapy context, confirming the value of their inclusion
      in clinical education programmes. Suggestions for improving the training of SPs
      in order to maintain accuracy are highlighted.

PMID- 24119131
TI  - Mechanisms of hemolysis-associated platelet activation.
AB  - BACKGROUND: Intravascular hemolysis occurs after blood transfusion, in hemolytic
      anemias, and in other conditions, and is associated with hypercoagulable states.
      Hemolysis has been shown to potently activate platelets in vitro and in vivo, and
      several mechanisms have been suggested to account for this, including: (i) direct
      activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS);
      (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of
      intraerythrocytic ADP. OBJECTIVE: To elucidate the mechanism of hemolysis
      mediated platelet activation. METHODS: We used flow cytometry to detect PAC-1
      binding to activated platelets for in vitro experiments, and a Siemens' Advia 120
      hematology system to assess platelet aggregation by using platelet counts from in
      vivo experiments in a rodent model. RESULTS: We found that Hb did not directly
      activate platelets. However, ADP bound to Hb could cause platelet activation.
      Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was
      reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS
      scavengers did not affect platelet activation. We also found that cell-free Hb
      enhanced platelet activation by abrogating the inhibitory effect of NO on
      platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb, as well
      as hemolysate, resulted in platelet aggregation, as shown by decreased platelet
      counts. CONCLUSION: Two primary mechanisms account for RBC hemolysis-associated
      platelet activation: ADP release, which activates platelets; and cell-free Hb
      release, which enhances platelet activation by lowering NO bioavailability.

PMID- 24119133
TI  - Secreted single-stranded DNA is involved in the initial phase of biofilm
      formation by Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is an obligate human pathogen that colonizes the genital
      tract and causes gonorrhoea. Neisseria gonorrhoeae can form biofilms during
      natural cervical infections, on glass and in continuous flow-chamber systems.
      These biofilms contain large amounts of extracellular DNA, which plays an
      important role in biofilm formation. Many clinical isolates contain a gonococcal
      genetic island that encodes a type IV secretion system (T4SS). The T4SS of N.
      gonorrhoeae strain MS11 secretes ssDNA directly into the medium. Biofilm
      formation, studied in continuous flow-chamber systems by confocal laser scanning
      microscopy (CLSM), was strongly reduced, especially in the initial phases of
      biofilm formation, in the presence of Exonuclease I, which specifically degrades
      ssDNA or in a DeltatraB strain that does not secrete ssDNA. To specifically
      detect ssDNA in biofilms using CLSM, a novel method was developed in which
      thermostable fluorescently labelled ssDNA- and ss/dsDNA-binding proteins were
      used to visualize ssDNA and total DNA in biofilms and planktonic cultures.
      Remarkably, mainly dsDNA was detected in biofilms of the ssDNA secreting strain.
      We conclude that the secreted ssDNA facilitates initial biofilm formation, but
      that the secreted ssDNA is not retained in mature biofilms. 

PMID- 24119134
TI  - Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus
      aureus.
AB  - Drosophila haemocytes are essential for the animal to resist Staphylococcus
      aureus infections. Phagocytosis is a central component of the haemocyte-mediated
      immune response. It involves regulated interaction between the phagocytic and the
      endocytic compartments. RabGTPases are pivotal for the membrane trafficking and
      fusion events, and thus are often targets of intracellular pathogens that subvert
      phagocytosis. An in vivo screen identified Rab2 and Rab14 as candidates for
      proteins regulating phagosome maturation. Since Rab14 is often targeted by
      intracellular pathogens, an understanding of its function during phagocytosis and
      the overall immune response can give insight into the pathogenesis of
      intracellular microbes. We generated a Drosophila Rab14 mutant and characterized
      the resulting immune defects in animals and specifically in haemocytes in
      response to an S. aureus infection. Haemocyte based immunofluorescence studies
      indicate that Rab14 is recruited to the phagosome and like Rab7, a well
      characterized regulator of the phagocytic pathway, is essential for progression
      of phagosome maturation. Rab14 mutant haemocytes show impaired recruitment of
      Rab7 and of a lysosomal marker onto S. aureus phagosomes. The defect in
      phagocytosis is associated with higher bacterial load and increased
      susceptibility to S. aureus in the animal. 

PMID- 24119135
TI  - Conophylline suppresses hepatic stellate cells and attenuates thioacetamide
      induced liver fibrosis in rats.
AB  - BACKGROUND & AIMS: Conophylline (CnP) is a vinca alkaloid purified from a
      tropical plant and inhibits activation of pancreatic stellate cells. We
      investigated the effect of CnP on hepatic stellate cells (HSC) in vitro. We also
      examined whether CnP attenuates hepatic fibrosis in vivo. METHOD: We examined the
      effect of CnP on the expression of alpha-smooth muscle actin (alpha-SMA) and
      collagen-1, DNA synthesis and apoptosis in rat HSC and Lx-2 cells. We also
      examined the effect of CnP on hepatic fibrosis induced by thioacetamide (TAA).
      RESULTS: In rat HSC and Lx-2 cells, CnP reduced the expression of alpha-SMA and
      collagen-1. CnP inhibited DNA synthesis induced by serum. CnP also promoted
      activation of caspase-3 and induced apoptosis as assessed by DNA ladder formation
      and TUNEL assay. In contrast, CnP did not induce apoptosis in AML12 cells. We
      then examined the effect of CnP on TAA-induced cirrhosis. In TAA-treated rats,
      the surface of the liver was irregular and multiple nodules were observed.
      Histologically, formation of pseudolobules surrounded by massive fibrous tissues
      was observed. When CnP was administered together with TAA, the surface of the
      liver was smooth and liver fibrosis was markedly inhibited. Collagen content was
      significantly reduced in CnP-treated liver. CONCLUSION: Conophylline suppresses
      HSC and induces apoptosis in vitro. CnP also attenuates formation of the liver
      fibrosis induced by TAA in vivo.

PMID- 24119136
TI  - Exercise for mental illness: a systematic review of inpatient studies.
AB  - A substantial body of evidence supports the role of exercise interventions for
      people with a mental illness. However, much of this literature is conducted using
      outpatient and community-based populations. We undertook a systematic review
      examining the effect of exercise interventions on the health of people
      hospitalized with depression, schizophrenia, bipolar disorder, or anxiety
      disorders. Eight studies met our inclusion criteria. Several studies show
      positive health outcomes from short-term and long-term interventions for people
      hospitalized due to depression. Although positive, the evidence for inpatients
      with schizophrenia, bipolar disorder, or anxiety disorders is substantially less.
      There is an urgent need to address the paucity of literature in this area, in
      particular the optimal dose and delivery of exercise for people hospitalized as a
      result of mental illness. Standardization of reporting exercise programme
      variables, the assessment of mental illness, and the reporting of adverse events
      must accompany future studies. 

PMID- 24119137
TI  - Epithelial ingrowth - Nd:YAG laser approach.

PMID- 24119138
TI  - Differences in differential gene expression between young and mature Arabidopsis
      C58 tumours.
AB  - Tumorigenesis of plants triggered by Agrobacterium tumefaciens has been
      investigated for over a century, but a global study on changes in gene expression
      in plant tumours during growth and development has received little attention so
      far due to technical difficulties. Recently a great advance in 'omic'
      technologies, e.g. microarray, proteome and transcriptome analyses, has allowed
      differential expression profiling of genes for metabolic regulation during plant
      tumour growth and development. Deeken et al.(The Plant Cell Online, 18, 3617) and
      Lee C.-W. et al.(The Plant Cell Online, 21, 2948) used a fold change approach to
      profile genes differentially expressed (DE) between Arabidopsis inflorescence
      stalks infected with Agrobacterium strains C58 (carrying T-DNA) or GV3101
      (without T-DNA) and control stalks at 3 hours, 6 days and 35 days after
      inoculation. We utilised ranking analysis of microarray data, a modified t-test
      approach, to further analyse these microarray data and compared DE gene
      functioning in photosynthesis, energy, nucleotide, RNA, DNA, protein and lipid
      metabolism, biological defence, cell wall and signalling pathways in young (6-day
      old) and mature (35-day-old) tumours. There were large differences in
      differential expression of genes for these basic metabolic pathways between young
      and mature tumours. In young tumours, more genes were up-regulated in most
      metabolic functional categories than down-regulated, whereas in mature tumours,
      genes involved in basic and major metabolic pathways were more down-regulated
      than up-regulated, strongly indicating that relative to the control stalk, many
      metabolic pathways were enhance in young tumours but decayed or tended to be
      decayed in mature tumours.

PMID- 24119140
TI  - Deprivation and access to treatment for colorectal cancer in Southeast Scotland
      2003-2009.
AB  - AIM: Socioeconomic deprivation is associated with poorer survival from colorectal
      cancer. We examined the association of deprivation with access to treatment,
      disease stage at presentation and choice of treatment for colorectal cancer
      within a regional managed clinical network. METHOD: We performed a retrospective
      analysis of data from the Southeast Scotland Cancer Network colorectal database
      for the period 2003-2009. Socioeconomic status was assigned into five categories
      using postcode of residence and the Scottish Index of Multiple Deprivation score.
      Outcomes were access to consultation and treatment, stage of disease at
      presentation and treatment factors (type of surgery, adjuvant radiotherapy and
      adjuvant chemotherapy). RESULTS: Of 4960 colorectal cancer patients, 4016
      patients (81%) underwent operative treatment. Deprivation was not associated with
      age, gender, tumour site, disease stage, delay in treatment pathway or permanent
      stoma rate. Primary tumour resection (P = 0.006) and chemotherapy treatment (P =
      0.018) were higher in the least deprived compared with the most deprived
      quintile. Socioeconomic status was associated with both primary tumour resection
      [odds ratio for the most affluent compared with the most deprived quintiles (OR)
      1.34, 95% confidence interval (CI) 1.05-1.72, P = 0.018] and chemotherapy
      treatment (OR 1.44, 95% CI 1.15-1.80, P = 0.001). However, when health board of
      treatment was added to the model, only chemotherapy treatment was independently
      associated with deprivation (OR 1.46, 95% CI 1.16-1.83, P = 0.001). CONCLUSION:
      Deprivation is not associated with treatment delay or more advanced disease stage
      at presentation. An apparent association between deprivation and treatment choice
      may be explained by other differences between patients treated in different
      areas.

PMID- 24119139
TI  - Passive leg movement-induced hyperaemia with a spinal cord lesion: evidence of
      preserved vascular function.
AB  - A spinal cord injury (SCI) clearly results in greater cardiovascular risk;
      however, accompanying changes in peripheral vascular structure below the lesion
      mean that the real impact of a SCI on vascular function is unclear. AIM:
      Therefore, utilizing passive leg movement-induced (PLM) hyperaemia, an index of
      nitric oxide (NO)-dependent vascular function and the central hemodynamic
      response to this intervention, we studied eight individuals with a SCI and eight
      age-matched controls (CTRL). METHODS: Specifically, we assessed heart rate (HR),
      stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), leg blood
      flow (LBF) and thigh composition. RESULTS: In CTRL, passive movement transiently
      decreased MAP and increased HR and CO from baseline by 2.5 +/- 1 mmHg, 7 +/- 2
      bpm and 0.5 +/- 0.1 L min(-1) respectively. In SCI, HR and CO responses were
      unidentifiable. LBF increased to a greater extent in CTRL (515 +/- 41 ?mL min(
      1)) compared with SCI, (126 +/- 25 ?mL min(-1)) (P < 0.05). There was a strong
      relationship between ?LBF and thigh muscle volume (r = 0.95). After normalizing
      ?LBF for this strong relationship (?LBF/muscle volume), there was evidence of
      preserved vascular function in SCI (CTRL: 120 +/- 9; SCI 104 +/- 11 mL min(-1) L(
      1)). A comparison of ?LBF in the passively moved and stationary leg, to partition
      the contribution of the blood flow response, implied that 35% of the hyperaemia
      resulted from cardioacceleration in the CTRL, whereas all the hyperaemia appeared
      peripheral in origin in the SCI. CONCLUSION: Thus, utilizing PLM-induced
      hyperaemia as marker of vascular function, it is evident that peripheral vascular
      impairment is not an obligatory accompaniment to a SCI.

PMID- 24119141
TI  - Glistening in glaucomatous eyes: visual performances and risk factors.
AB  - PURPOSE: To analyse risk factors and visual performances of glaucomatous eyes
      with glistening in the intra-ocular lens (IOL). METHODS: Prospective study
      performed between November 2010 and April 2011 and involving 67 consecutive
      glaucomatous eyes (47 patients), who previously had a phacoemulsification with a
      hydrophobic acrylic IOL implanted in the capsular bag. Glistening was classified
      in three groups of severity grade: G0 (<50 microvacuoles per mm(2) ), G1 (50-150
      microvacuoles per mm(2) ), and G2 (>150 microvacuoles per mm(2) ). All eyes
      underwent a best-corrected visual acuity evaluation (BCVA, LogMAR scale), a
      complete clinical examination, a visual field test, a contrast sensitivity
      evaluation and a wavefront analysis of high-order aberrations (HOAs) using a
      Shack-Hartmann aberrometer. Eyes with a posterior capsular opacification and a
      BCVA>0.30 LogMAR were excluded. RESULTS: Twenty six eyes (38.8%) had a grade 0,
      12 eyes (17.9%) a grade 1 and 29 eyes (43.3%) a grade 2 of glistening severity
      grade. The mean follow-up after cataract surgery was 35.2 +/- 24.2 months and was
      significantly higher for G1 and G2 groups (p < 0.001). A higher number of topical
      glaucoma medication were associated with a higher glistening severity grade (p <
      0.05). G1 and G2 groups had significantly lower mean contrast sensitivity values
      at high spatial frequencies and significantly higher loss variance (LV) values of
      the visual field test (p < 0.05). There was no significant difference in mean
      BCVA between groups (p = 0.455). CONCLUSIONS: In glaucomatous eyes, glistening
      increased with time was associated with the number of topical glaucoma
      medications daily instilled and altered visual performances. It should be a
      consideration for glaucoma patients who are more likely to develop glistening
      within the IOL optic.

PMID- 24119142
TI  - Structural insights into the oligomerization mode of the human receptor for
      advanced glycation end-products.
AB  - The receptor for advanced glycation end-products (RAGE) is a pattern recognition
      receptor sensing endogenous stress signals associated with the development of
      various diseases, including diabetes, vascular complications, Alzheimer's disease
      and cancer. RAGE ligands include advanced glycation end-products, S100 proteins,
      high mobility group box 1 protein and amyloid beta-peptides/fibrils. Their
      signalling through RAGE induces a sustained inflammation that accentuates tissue
      damage, thereby participating in disease progression. Receptor oligomerization
      appears to be a crucial parameter for the formation of active signalling
      complexes, although the precise mode of oligomerization remains unclear in the
      context of these various ligands. In the present study, we report the first
      crystal structure of the VC1C2 fragment of the RAGE ectodomain. This structure
      provides the first description of the C2 domain in the context of the entire
      ectodomain and supports the observation of its conformational freedom relative to
      the rigid VC1 domain tandem. In addition, we have obtained a new crystal
      structure of the RAGE VC1 fragment. The packing in both crystal structures
      reveals an association of the RAGE molecules through contacts between two V
      domains and the physiological relevance of this homodimerization mode is
      discussed. Based on homology with single-pass transmembrane receptors, we also
      suggest RAGE dimerization through a conserved GxxxG motif within its
      transmembrane domain. A multimodal homodimerization strategy of RAGE is proposed
      to form the structural basis for ligand-specific complex formation and signalling
      functions, as well as for RAGE-mediated cell adhesion. STRUCTURED DIGITAL
      ABSTRACT: hRAGE_VC1C2 and hRAGE_VC1C2 bind by x-ray crystallography (View
      interaction) hRAGE_VC1 and hRAGE_VC1 bind by x-ray crystallography (View
      interaction).

PMID- 24119143
TI  - Accuracy of MRI technique in measuring tendon cross-sectional area.
AB  - Magnetic resonance imaging (MRI) has commonly been applied to determine tendon
      cross-sectional area (CSA) and length either to measure structural changes or to
      normalize mechanical measurements to stress and strain. The ability to reproduce
      CSA measurements on MRI images has been reported, but the accuracy in relation to
      actual tendon dimensions has never been investigated. The purpose of this study
      was to compare tendon CSA measured by MRI with that measured in vitro with the
      mould casting technique. The knee of a horse was MRI-scanned with 1.5 and 3
      tesla, and two examiners measured the patellar tendon CSA. Thereafter, the
      patellar tendon of the horse was completely dissected and embedded in an alginate
      cast. The CSA of the embedded tendon was measured directly by optical imaging of
      the cast impression. 1.5 tesla grey tendon CSA and 3 tesla grey tendon CSA were
      16.5% and 13.2% lower than the mould tendon CSA, respectively. Also, 3 tesla
      tendon CSA, based on the red-green border on the National Institute of Health
      (NIH) colour scale, was lower than the mould tendon CSA by 2.8%. The typical
      error between examiners was below 2% for all the measured CSA. The typical error
      between examiners was below 2% for all the measured CSA. These data show that
      measuring tendon CSA on the grey-scale MRI images is associated with an
      underestimation, but by optimizing the measurement using a 3 tesla MRI and the
      appropriate NIH colour scale, this underestimation could be reduced to 2.8%
      compared with the direct measurements on the mould. 

PMID- 24119144
TI  - The impact of length and location of positive margins in predicting biochemical
      recurrence after robot-assisted radical prostatectomy with a minimum follow-up of
      5 years.
AB  - OBJECTIVE: To evaluate the role of positive surgical margin (PSM) size/focality
      and location in relation to risk of biochemical recurrence (BCR) after robot
      assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Clinicopathological
      data were collected from 904 patients who underwent RARP at a single European
      institution from 2002 to 2006. PSM status after RARP was defined as cancer cells
      at the inked margin, and was stratified by size/focality and location. The
      outcome variable was BCR, defined as a postoperative PSA level of >=0.2 ng/mL. We
      modelled clinicopathological covariates including PSM size/focality and location
      using Cox proportional hazards regression. In subgroup analyses, we assessed the
      effect of PSM size and location at different pathological stages and grades of
      disease. RESULTS: Compared with negative SM, a PSM of >3 mm/multifocal was
      associated with an increased risk of BCR in the entire cohort (hazard ratio [HR]
      2.84, 95% confidence interval 1.76-4.59), while unifocal PSMs of <=3 mm were not
      significantly associated with BCR. In subgroup analyses, the negative impact of
      >3 mm/multifocal PSM appeared greatest in those with lower postoperative stage
      and grade of disease. The prognostic role of PSM location was unconfirmed,
      although data indicated that posterolateral PSMs may be of lower significance in
      RARP patients. The study is limited by lack of central pathology review, and lack
      of statistical adjustment for tumour volume, lymph node status, and surgeon
      volume. CONCLUSION: We found that men with >3 mm/multifocal PSMs have a higher
      risk of BCR than those with unifocal PSMs of <=3 mm or negative SMs, especially
      if they have lower risk disease. Posterolateral margins may be of little
      significance in a RARP population.

PMID- 24119146
TI  - When the newborn does not breathe and there is no resuscitation equipment.

PMID- 24119147
TI  - Peyronie's disease plaque calcification--prevalence, time to identification, and
      development of a new grading classification.
AB  - INTRODUCTION: Peyronie's disease (PD) is a connective tissue disorder of the
      penis in which a fibrous scar in the tunica albuginea can result in multiple
      penile deformities. AIM: The study aims to investigate the prevalence and time to
      identification of plaque calcification (PC) in our PD patient population and
      whether stratification of calcification based on severity seen on ultrasound
      would serve as a predictor of treatment progression to surgery. METHODS: A
      retrospective review of 1,041 men presenting with PD from 1993 to 2009 was
      performed. Eight hundred thirty-four underwent penile duplex ultrasound. MAIN
      OUTCOME MEASURES: PC was graded as: grade 1 (<0.3 cm), grade 2 (>0.3 cm, <1.5
      cm), grade 3 (>1.5 cm; or >= 2 plaques >1.0 cm). A matched control group with
      noncalcified plaques (n = 236) was selected for comparison. RESULTS: Two hundred
      eighty-four men (34%) were found to have PC noted on ultrasound, and 98 had fully
      documented dimensions of the PC. Forty-one percent were found to have grade 1,
      28% grade 2, and 32% grade 3. When analyzed by grade and progression to surgery,
      23% of grade 1, 32% of grade 2, and 55% of grade 3 patients had surgery. Those
      with grade 3 PC were more likely to undergo surgical intervention for PD (OR 2.28
      95% CI 1.07-4.86) and more likely to undergo a grafting procedure than control
      patients (P < 0.0001). CONCLUSIONS: Men with PC are not more likely to undergo
      surgery than those without PC (OR 0.95, 95% CI 0.58-1.57). PC is not uncommon, as
      it was found in 34% of our cohort. PC does not appear to be an indication of
      mature or stable disease, as it was identified by ultrasound in 37% of patients
      less than 12 months after onset of symptoms. Men with grade 3 PC have an
      increased likelihood of progression to surgical intervention and a higher
      likelihood of undergoing a grafting procedure.

PMID- 24119145
TI  - Transcriptional profile of Paracoccidioides induced by oenothein B, a potential
      antifungal agent from the Brazilian Cerrado plant Eugenia uniflora.
AB  - BACKGROUND: The compound oenothein B (OenB), which is isolated from the leaves of
      Eugenia uniflora, a Brazilian Cerrado plant, interferes with Paracoccidioides
      yeast cell morphology and inhibits 1,3-beta-D-glucan synthase (PbFKS1) transcript
      accumulation, which is involved in cell wall synthesis. In this work we examined
      the gene expression changes in Paracoccidioides yeast cells following OenB
      treatment in order to investigate the adaptive cellular responses to drug stress.
      RESULTS: We constructed differential gene expression libraries using
      Representational Difference Analysis (RDA) of Paracoccidioides yeast cells
      treated with OenB for 90 and 180 min. Treatment for 90 min resulted in the
      identification of 463 up-regulated expressed sequences tags (ESTs) and 104 down
      regulated ESTs. For the 180 min treatment 301 up-regulated ESTs and 143 down
      regulated were identified. Genes involved in the cell wall biosynthesis, such as
      GLN1, KRE6 and FKS1, were found to be regulated by OenB. Infection experiments in
      macrophages corroborated the in vitro results. Fluorescence microscopy showed
      increased levels of chitin in cells treated with OenB. The carbohydrate polymer
      content of the cell wall of the fungus was also evaluated, and the results
      corroborated with the transcriptional data. Several other genes, such as those
      involved in a variety of important cellular processes (i.e., membrane
      maintenance, stress and virulence) were found to be up-regulated in response to
      OenB treatment. CONCLUSIONS: The exposure of Paracoccidioides to OenB resulted in
      a complex altered gene expression profile. Some of the changes may represent
      specific adaptive responses to this compound in this important pathogenic fungus.

PMID- 24119148
TI  - Glomerular filtration rate is an independent factor of mortality in patients with
      decompensated cirrhosis.
AB  - AIM: Although serum creatinine is included in the Model for End-Stage Liver
      Disease (MELD) score, it is an inaccurate marker of renal function, namely, of
      glomerular filtration rate ("true" GFR) in patients with decompensated cirrhosis.
      Our aim was to investigate the impact of MELD score and "true" GFR as
      determinants of survival in patients with decompensated cirrhosis. METHODS: We
      included all consecutive patients with decompensated cirrhosis who were admitted
      to our department. Renal function was assessed by creatinine- and cystatin-based
      estimated GFR and "true" GFR using (51) Cr-ethylenediaminetetraacetic acid. The
      independent factors associated with survival were evaluated. The discriminative
      ability of the prognostic scores (MELD and modifications of MELD score) were
      evaluated by using the area under the receiver-operator curve (AUC). RESULTS: One
      hundred and ten consecutive patients (77 men, aged 56 +/- 12 years); at the end
      of follow up (8 months; range, 6-18), 92 patients (84%) were alive and 18 (16%)
      had died. In multivariate analysis, serum bilirubin (hazard ratio [HR], 1.15; 95%
      confidence interval [CI], 1.05-1.26; P = 0.020) and "true" GFR (HR, 0.96; 95% CI,
      0.93-0.98; P = 0.003) were the only independent factors significantly associated
      with the outcome. The derived new prognostic model had high discriminative
      ability (AUC, 0.90), which was confirmed in the validation sample of 77 patients.
      CONCLUSION: In our cohort of patients with decompensated cirrhosis, "true" GFR
      and bilirubin were the independent factors of the outcome.

PMID- 24119149
TI  - The effect of vitamin D on nonspecific low back pain.
AB  - BACKGROUND: Nonspecific low back pain is known as one of the most common reasons
      for chronic low back pain (CLBP) that burdens healthcare systems with high costs.
      According to a hypothesis, CLBP has been associated with vitamin D3 deficiency,
      the goal of this study is to evaluate the effect of vitamin D3 administration on
      improvements in CLBP. MATERIALS AND METHODS: This double blind randomized
      clinical trial included 53 patients aged between 18-40 years with nonspecific
      CLBP. Pain was measured using the pain visual analogue scale score (VAS), and
      serum 25-OH-vitamin D level was measured using an enzyme-linked immunosorbent
      assay kit. The patients were randomly divided into two groups based on sex and
      weight. Pearl of vitamin D(3) (50 000 IU) or placebo was administered orally
      every week for 8 weeks. Data were analyzed via SPSS 17th edition software using
      two-tailed paired t-test and chi-square test. RESULTS: There were 26 and 27
      patients in drug and placebo groups respectively. Out of 53 subjects, 75.47% were
      female. There was no statistically significant difference in the mean age, sex,
      and mean weight between the two groups. The mean serum 25-OH-vitamin D level was
      18.86 +/- 9.24 nmol/L on the first visit. After 8 weeks of intervention, the mean
      serum 25-OH-vitamin D level changed from 17.88 +/- 9.04 to 27.52 +/- 9.04 (P =
      0.043) and from 19.81 +/- 9.60 to 18.91 +/- 7.84 (P = 0.248) in drug and placebo
      groups, respectively. The mean VAS score for pain decreased from 5.42 +/- 1.65 to
      3.03 +/- 3.14 (P = 0.001) and from 6.42 +/- 1.62 to 3.11 +/- 3.08 (P = 0.001)
      among drug and placebo groups, respectively. The mean changes in chronic pain
      were 2.38 +/- 2.62, 95% confidence interval (CI) = 1.32-3.44 in the drug group
      and 3.33 +/- 3.67, 95%CI = 0.61-2.55 in the placebo group. No significant
      statistical difference between the two groups was observed. CONCLUSION: According
      to our results, both vitamin D(3) and placebo treatments improved CLBP and there
      was no significant difference between vitamin D(3) and placebo groups.

PMID- 24119150
TI  - Abnormalities of brain response during encoding into verbal working memory among
      euthymic patients with bipolar disorder.
AB  - OBJECTIVES: Individuals with bipolar disorder (BD) have trait-like deficits in
      attention and working memory (WM). A fundamental dissociation for most verbal WM
      theories involves the separation of sensory-perceptual encoding, reliant upon
      attention, from the maintenance of this information in WM proper. The present
      study examined if patients with BD demonstrate differential neural changes in
      encoding and maintenance WM processes that underlie cognitive impairment.
      METHODS: Event-related functional magnetic resonance imaging during a delayed
      match-to-sample WM paradigm was employed in 23 inter-episode medicated patients
      with BD and 23 demographically similar healthy comparison participants. We
      examined brain regions during encoding and maintenance task intervals to identify
      regions that demonstrated differential effects between groups. Medication effects
      and functional connectivity between prefrontal cortex and basal ganglia/thalamus
      were examined during the encoding interval due to the importance of these regions
      and the connection among them for encoding into WM. RESULTS: Patients with BD
      exhibited deficits in task accuracy and attenuated brain response during the
      encoding interval in areas of the prefrontal cortex, caudate, thalamus, and
      posterior visual regions. In contrast, patients with BD exhibited hyperactivation
      in posterior sensory regions during the maintenance interval. Among the BD group,
      those with greater medication load exhibited the greatest brain response within
      the prefrontal cortex. CONCLUSIONS: Reduction in activation during the encoding
      interval suggests that attentional deficits underlie WM deficits in patients with
      BD. These deficits appear to be trait-like in so far as they were observed during
      periods of euthymia in patients with BD. Medication effects remain to be further
      explored as there was evidence of prefrontal changes dependent on medication
      load.

PMID- 24119151
TI  - A dsRNA-binding protein MdDRB1 associated with miRNA biogenesis modifies
      adventitious rooting and tree architecture in apple.
AB  - Although numerous miRNAs have been already isolated from fruit trees, knowledge
      about miRNA biogenesis is largely unknown in fruit trees. Double-strand RNA
      binding (DRB) protein plays an important role in miRNA processing and maturation;
      however, its role in the regulation of economically important traits is not clear
      yet in fruit trees. EST blast and RACE amplification were performed to isolate
      apple MdDRB1 gene. Following expression analysis, RNA binding and protein
      interaction assays, MdDRB1 was transformed into apple callus and in vitro tissue
      cultures to characterize the functions of MdDRB1 in miRNA biogenesis,
      adventitious rooting, leaf development and tree growth habit. MdDRB1 contained
      two highly conserved DRB domains. Its transcripts existed in all tissues tested
      and are induced by hormones. It bound to double-strand RNAs and interacted with
      AtDCL1 (Dicer-Like 1) and MdDCL1. Chip assay indicated its role in miRNA
      biogenesis. Transgenic analysis showed that MdDRB1 controls adventitious rooting,
      leaf curvature and tree architecture by modulating the accumulation of miRNAs and
      the transcript levels of miRNA target genes. Our results demonstrated that MdDRB1
      functions in the miRNA biogenesis in a conserved way and that it is a master
      regulator in the formation of economically important traits in fruit trees. 

PMID- 24119153
TI  - Review of recent literature in hypertension: updated clinical practice guidelines
      for chronic kidney disease now include albuminuria in the classification system.

PMID- 24119152
TI  - IFN-gamma blocks CD4+CD25+ Tregs and abolishes immune privilege of minor
      histocompatibility mismatched corneal allografts.
AB  - Th1 CD4+ cells are believed to be the primary mediators of corneal allograft
      rejection. However, rejection of fully allogeneic C57BL/6 corneal allografts
      soared from 50% to 90% in both interferon-gamma (IFN-gamma)(-/-) and anti-IFN
      gamma-treated BALB/c mice. In contrast, similar deficits in IFN-gamma in BALB/c
      hosts enhanced immune privilege of BALB.B (minor histocompatibility [minor H]
      antigen-matched, major histocompatibility complex [MHC]-mismatched) and NZB (MHC
      matched, minor H antigen-mismatched) corneal allografts-decreasing rejection from
      80% to ~20%. This effect of IFN-gamma was independent of CD4+ T cell lineage
      commitment as both anti-IFN-gamma-treated acceptor and rejector mice displayed a
      Th2 cytokine profile. The presence of IFN-gamma prevented the generation of
      alloantigen-specific CD4+CD25+ T regulatory cells (Tregs) in hosts receiving
      either MHC only mismatched BALB.B or minor only histocompatibility (minor H)
      mismatched NZB corneal allografts. Tregs in these hosts promoted corneal
      allograft survival by suppressing Th2 effector cells. By contrast, IFN-gamma was
      necessary for the generation of CD4+CD25+ Tregs that prevented rejection of fully
      allogeneic C57BL/6 corneal allografts in BALB/c hosts. These findings suggest
      that MHC-matching in combination with blockade of IFN-gamma holds promise as a
      means of enhancing corneal allograft survival.

PMID- 24119154
TI  - Detecting an elusive invasive species: a diagnostic PCR to detect Burmese python
      in Florida waters and an assessment of persistence of environmental DNA.
AB  - Recent studies have demonstrated that detection of environmental DNA (eDNA) from
      aquatic vertebrates in water bodies is possible. The Burmese python, Python
      bivittatus, is a semi-aquatic, invasive species in Florida where its elusive
      nature and cryptic coloration make its detection difficult. Our goal was to
      develop a diagnostic PCR to detect P. bivittatus from water-borne eDNA, which
      could assist managers in monitoring this invasive species. First, we used captive
      P. bivittatus to determine whether reptilian DNA could be isolated and amplified
      from water samples. We also evaluated the efficacy of two DNA isolation methods
      and two DNA extraction kits commonly used in eDNA preparation. A fragment of the
      mitochondrial cytochrome b gene from P. bivittatus was detected in all water
      samples isolated with the sodium acetate precipitate and the QIAamp DNA Micro
      Kit. Next, we designed P. bivittatus-specific primers and assessed the
      degradation rate of eDNA in water. Our primers did not amplify DNA from closely
      related species, and we found that P. bivittatus DNA was consistently detectable
      up to 96 h. Finally, we sampled water from six field sites in south Florida.
      Samples from five sites, where P. bivittatus has been observed, tested positive
      for eDNA. The final site was negative and had no prior documented evidence of P.
      bivittatus. This study shows P. bivittatus eDNA can be isolated from water
      samples; thus, this method is a new and promising technique for the management of
      invasive reptiles. 

PMID- 24119155
TI  - Characteristic structural features of indolicidin: effects of the cis-trans
      isomerism on its conformation.
AB  - Indolicidin is an antimicrobial peptide showing a broad spectrum of antibacterial
      and antifungal activities, and according to the cis-trans isomerism of three Xaa
      Pro peptide bonds, eight different stereoisomers could be distinguished for this
      peptide. As the cis-trans isomerism about the Xaa-Pro peptide bonds was not
      considered in previous studies, the structural features of distinct
      stereoisomeric forms were not characterized in detail, so far. In this
      theoretical study, the influences of cis-trans isomerism on the conformation of
      indolicidin were investigated, as well as the typical structural properties of
      each stereoisomer were determined, focusing on the secondary structures and
      intramolecular interactions. Based on the results derived from the molecular
      dynamics simulations, it could be concluded that the eight different
      stereoisomeric forms of indolicidin adopted characteristic conformational
      features. Nevertheless, the appearance of various turn structures and
      intramolecular interactions proved to be dependent on the cis or trans nature of
      Xaa-Pro peptide bonds, indicating the relevant role of Pro amino acids in
      determining the three-dimensional structure of this peptide. 

PMID- 24119156
TI  - Paraneoplastic pemphigus as the first manifestation of follicular dendritic cell
      sarcoma.

PMID- 24119157
TI  - Models of interinstitutional partnerships between research intensive universities
      and minority serving institutions (MSI) across the Clinical Translational Science
      Award (CTSA) consortium.
AB  - Health disparities are an immense challenge to American society. Clinical and
      Translational Science Awards (CTSAs) housed within the National Center for
      Advancing Translational Science (NCATS) are designed to accelerate the
      translation of experimental findings into clinically meaningful practices and
      bring new therapies to the doorsteps of all patients. Research Centers at
      Minority Institutions (RCMI) program at the National Institute on Minority Health
      and Health Disparities (NIMHD) are designed to build capacity for biomedical
      research and training at minority serving institutions. The CTSA created a
      mechanism fostering formal collaborations between research intensive universities
      and minority serving institutions (MSI) supported by the RCMI program. These
      consortium-level collaborations activate unique translational research approaches
      to reduce health disparities with credence to each academic institutions history
      and unique characteristics. Five formal partnerships between research intensive
      universities and MSI have formed as a result of the CTSA and RCMI programs. These
      partnerships present a multifocal approach; shifting cultural change and
      consciousness toward addressing health disparities, and training the next
      generation of minority scientists. This collaborative model is based on the
      respective strengths and contributions of the partnering institutions, allowing
      bidirectional interchange and leveraging NIH and institutional investments
      providing measurable benchmarks toward the elimination of health disparities. 

PMID- 24119158
TI  - A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe
      abdominal Aortic calcification in stage 3 and 4 kidney disease patients.
AB  - BACKGROUND: Vascular calcification (VC) contributes to high mortality rates in
      chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired
      phosphaturic response to FGF23 may affect VC. Therefore, their relative
      contribution to abdominal aortic calcification (AAC) was examined in patients CKD
      stages 3-4. METHODS: Potential risk factors for AAC, measured by the Kauppila
      Index (KI), were studied in 178 patients. RESULTS: In multivariate linear
      analysis, AAC associated positively with age, male gender, CKD-stage, presence of
      carotid plaques (CP) and also with FGF23, but negatively with fractional
      excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes
      with elevations in PTH, with reductions in GFR, and also with elevations in FGF23
      but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack
      of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role
      for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic
      and zero-inflated analysis confirmed the independent association of age, CKD
      stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23
      ratio of 1/3.9, below which the chances for a patient of presenting severe AAC
      increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios
      decreased from 1/1 to 1/3.9 but markedly increased in parallel with further
      reductions in FEP/FGF23 < 1/3.9. CONCLUSIONS: In CKD 3-4, an impaired
      phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC
      independently of age, gender or CP.

PMID- 24119159
TI  - Solvent-exposed serines in the Gal4 DNA-binding domain are required for promoter
      occupancy and transcriptional activation in vivo.
AB  - The yeast transcriptional activator Gal4 has long been the prototype for studies
      of eukaryotic transcription. Gal4 is phosphorylated in the DNA-binding domain
      (DBD); however, the molecular details and functional significance of this remain
      unknown. We mutagenized seven potential phosphoserines that lie on the solvent
      exposed face of the DBD structure and assessed them for transcriptional activity
      and DNA binding in vivo. Serine to alanine mutants at positions 22, 47, and 85
      show the greatest reduction in promoter occupancy and transcriptional activity at
      the MEL1 promoter containing a single UASGAL . Substitutions with the
      phosphomimetic aspartate restored DNA-binding and transcriptional activity at
      serines 22 and 85, suggesting that they are potential sites of Gal4
      phosphorylation in vivo. In contrast, the serine to alanine mutants, except
      serine 22, were fully proficient for binding to the GAL1-10 promoter, containing
      multiple UASGAL sites, although they had a reduced ability to activate
      transcription. Collectively, these data show that at the GAL1-10 promoter,
      functions of the DBD in transcriptional activation can be uncoupled from roles in
      promoter binding. We suggest that the serines in the DBD mediate protein-protein
      contacts with the transcription machinery, leading to stabilization of Gal4 at
      promoters. 

PMID- 24119160
TI  - Prevalence of MRI-detected mediopatellar plica in subjects with knee pain and the
      association with MRI-detected patellofemoral cartilage damage and bone marrow
      lesions: data from the Joints On Glucosamine study.
AB  - BACKGROUND: The mediopatellar plica is a synovial fold representing an embryonic
      remnant from the developmental process of the synovial cavity formation in the
      knee. We aimed to examine the frequency of MRI-detected mediopatellar plica and
      its cross-sectional association with MRI-detected cartilage damage and bone
      marrow lesions (BMLs) in the patellofemoral joint (PFJ) in a cohort of subjects
      with knee pain. METHODS: 342 knees with chronic frequent knee pain were evaluated
      for MRI-detected mediopatellar plica (type A, B or C according to the modified
      Sakakibara classification). Cartilage damage (scored 0 to 6) and BMLs (scored 0
      to 3) were semiquantitatively assessed in four subregions of the PFJ on MRI.
      Hoffa-synovitis and effusion-synovitis were graded 0 to 3. Patellar length ratio
      (PLR), lateral patellar tilt angle (LPTA), bisect offset (BO), and sulcus angle
      (SA) were measured on MRI. The presence of mediopatellar plica and its
      association with cartilage damage and BMLs in the PFJ was assessed using logistic
      regression after adjusting for age, gender, body mass index, PLR, LPTA, BO, SA,
      and Hoffa- and effusion-synovitis. RESULTS: 163 (47.7%) knees exhibited
      mediopatellar plica (76 (22.2%) type A, 69 (20.2%) type B, and 18 (5.3%) type C)
      on MRI. Significant cross-sectional associations of MRI-detected mediopatellar
      plica and cartilage damage were observed for the medial patella (adjusted odds
      ratio (aOR) 2.12, 95% CI 1.23-3.64 for all types combined, and aOR 4.20, 95% CI
      1.92-9.19 for type B lesion), but not for the anterior medial femur or the
      lateral PFJ. No associations were found between the presence of MRI-detected
      mediopatellar plica and BMLs in any patellofemoral subregion. CONCLUSION: On MRI,
      types A and B mediopatellar plicae were commonly observed in this cohort of
      subjects with knee pain. MRI-detected mediopatellar plica was cross-sectionally
      associated with higher likelihood of the presence of MRI-detected medial patellar
      cartilage damage after adjustment for confounders.

PMID- 24119161
TI  - Panaxatriol saponin ameliorated liver injury by acetaminophen via restoring
      thioredoxin-1 and pro-caspase-12.
AB  - BACKGROUND & AIMS: Acetaminophen (APAP) is widely used as an antipyretic agent
      which is safe at therapeutic doses. However, overdose of APAP induces fatal and
      non-fatal hepatic necroses. The chemical reactive metabolites of APAP initiate
      toxicity and inflammatory response within the liver and lead to acute liver
      failure. However, the mechanism underlying APAP-induced liver injury is unknown.
      Thioredoxin-1 (TRX-1) is an important redox regulator, which plays roles in
      resisting oxidative stress, regulating inflammation and inhibiting apoptosis.
      Panaxatriol saponin (PTS) is one of the biologically active fractions of Panax
      notoginseng which is a traditional Chinese medicine. The aim of this study was to
      investigate the mechanism on PTS protecting liver from APAP hepatotoxicity.
      METHODS: Mice were divided into three groups, control group, APAP group and APAP
      combined with PTS group. Alanine aminotransferase (ALT) and tumour necrosis
      factor-alpha (TNF-alpha) were detected by ELISA. TRX-1 and pro-caspase-12 were
      examined by Western blotting. RESULTS: Our results showed PTS inhibited the
      levels of ALT and TNF-alpha by APAP. Pretreatment with PTS ameliorated liver
      injury induced by APAP. The decrease in TRX-1 expression was restored by PTS, as
      well as decreased pro-caspase-12 expression was inhibited by PTS. These data
      suggest that PTS has roles in suppressing the hepatotoxicity by APAP. CONCLUSION:
      Panaxatriol saponin ameliorated liver injury by APAP through restoring the
      expression TRX-1 and inhibiting pro-caspase-12 decrease.

PMID- 24119162
TI  - Sustainable remediation: electrochemically assisted microbial dechlorination of
      tetrachloroethene-contaminated groundwater.
AB  - Microbial electric systems (MESs) hold significant promise for the sustainable
      remediation of chlorinated solvents such as tetrachlorethene (perchloroethylene,
      PCE). Although the bio-electrochemical potential of some specific bacterial
      species such as Dehalcoccoides and Geobacteraceae have been exploited, this
      ability in other undefined microorganisms has not been extensively assessed.
      Hence, the focus of this study was to investigate indigenous and potentially bio
      electrochemically active microorganisms in PCE-contaminated groundwater. Lab
      scale MESs were fed with acetate and carbon electrode/PCE as electron donors and
      acceptors, respectively, under biostimulation (BS) and BS-bioaugmentation (BS-BA)
      regimes. Molecular analysis of the indigenous groundwater community identified
      mainly Spirochaetes, Firmicutes, Bacteroidetes, and gamma and delta
      Proteobacteria. Environmental scanning electron photomicrographs of the anode
      surfaces showed extensive indigenous microbial colonization under both regimes.
      This colonization and BS resulted in 100% dechlorination in both treatments with
      complete dechlorination occurring 4 weeks earlier in BS-BA samples and up to 11.5
      MUA of current being generated. The indigenous non-Dehalococcoides community was
      found to contribute significantly to electron transfer with ~61% of the current
      generated due to their activities. This study therefore shows the potential of
      the indigenous non-Dehalococcoides bacterial community in bio-electrochemically
      reducing PCE that could prove to be a cost-effective and sustainable
      bioremediation practice. 

PMID- 24119163
TI  - Clustering, persistence and control of a pollinator brood disease: epidemiology
      of American foulbrood.
AB  - American foulbrood (AFB), caused by Paenibacillus larvae, is the most damaging
      bacterial brood disease of the honeybee (Apis mellifera), causing colony deaths
      on all continents where honeybees are managed. AFB has been a persistent problem
      in the UK for over 70 years, with a fluctuating number of cases discovered
      annually. Once diseased colonies are identified, they are destroyed to reduce
      pathogen spread. We investigated the pattern of AFB cases recorded over the
      period 1994 to 2012 using spatial-statistical approaches, with a view to
      identifying the nature of spread across England and Wales. Our results indicated
      that AFB exhibits significant spatial aggregation at distances from 10 to 30 km,
      with aggregations lasting between 1 and 5 years. Kernel smoothing indicated areas
      of elevated relative risk in different years, and these were further detailed by
      spatial-scan statistics. We identified disease clusters and successfully
      estimated their size, location and duration. The majority of clusters did not
      persist in all years, indicating that management measures may lead to localized
      extinction of the disease. Whilst less common, persistent clusters likely
      indicate potential endemic or exotic risk points. The application of robust
      epidemiological approaches to improve the control of AFB is discussed.

PMID- 24119164
TI  - Pathophysiological mechanisms in acute mountain sickness.

PMID- 24119165
TI  - A 10-year experience of outcome in chemotherapy-treated hereditary
      retinoblastoma.
AB  - PURPOSE: The aim is to report the 10-year retrospective experience of systemic
      chemotherapy for a population-based group of patients with hereditary
      retinoblastoma at a national referral centre. The outcomes include control rates,
      treatment side-effects, adjuvant therapy, failure rate, survival, secondary
      cancers and visual acuity. METHODS: All patients (n = 24, 46 eyes) diagnosed with
      retinoblastoma and treated with systemic chemotherapy at a national referral
      centre during 2001-2011 were included. Data were extracted from medical records.
      RESULTS: The patients were followed for a mean of 60 months (range 13-144). Four
      six cycles of VEC was administered to all newly diagnosed group B/C/D/E eyes with
      bilateral disease and 83% (38 of 46) responded to the treatment. None of the
      patients discontinued chemotherapy because of adverse reactions. Altogether 26%
      (12 of 46) of the eyes received second-line therapy (other than thermotherapy,
      cryotherapy and chemotherapy). The failure rate was 35% (16 of 46) and mortality
      rate 0%. None of the patients developed CNS manifestations (metastases or
      trilateral retinoblastoma). One of the patients developed a second primary tumour
      (osteosarcoma) 4 years following retinoblastoma diagnosis. Altogether 17% (4 of
      24) patients received radiation therapy, 28% (13 of 46) of the eyes had to be
      enucleated, and one patient underwent bilateral enucleation. The age-correlated
      visual acuity was mean of 73% of expected visual acuity. CONCLUSION: Group A/B
      retinoblastomas have a distinct chemotherapy response, while group C/D/E tumours
      do not respond as well. The success rate was 65%; while patients have a good
      prognosis for life, approximately one-third of all hereditary cases received
      radiation therapy or underwent enucleation.

PMID- 24119166
TI  - Analysis of SecA2-dependent substrates in Mycobacterium marinum identifies
      protein kinase G (PknG) as a virulence effector.
AB  - The pathogenicity of mycobacteria is closely associated with their ability to
      export virulence factors. For this purpose, mycobacteria possess different
      protein secretion systems, including the accessory Sec translocation pathway,
      SecA2. Although this pathway is associated with intracellular survival and
      virulence, the SecA2-dependent effector proteins remain largely undefined. In
      this work, we studied a Mycobacterium marinum secA2 mutant with an impaired
      capacity to initiate granuloma formation in zebrafish embryos. By comparing the
      proteomic profile of cell envelope fractions from the secA2 mutant with wild type
      M. marinum, we identified putative SecA2-dependent substrates. Immunoblotting
      procedures confirmed SecA2-dependent membrane localization for several of these
      proteins, including the virulence factor protein kinase G (PknG). Interestingly,
      phenotypical defects of the secA2 mutant are similar to those described for
      DeltapknG, including phagosomal maturation. Overexpression of PknG in the secA2
      mutant restored its localization to the cell envelope. Importantly, PknG
      overexpression also partially restored the virulence of the secA2 mutant, as
      indicated by enhanced infectivity in zebrafish embryos and restored inhibition of
      phagosomal maturation. These results suggest that SecA2-dependent membrane
      localization of PknG is an important determinant for M. marinum virulence. 

PMID- 24119167
TI  - Interaction of the antibiotic minocycline with liver mitochondria - role of
      membrane permeabilization in the impairment of respiration.
AB  - Several studies have proposed that the antibiotic minocycline (MC) has
      cytoprotective activities. Nevertheless, when cells have been exposed to MC at
      micromolar concentrations, detrimental effects have been also observed. Despite
      the known inhibitory activity of MC on ATP synthesis and the Ca(2+) retention
      capacity of isolated rat liver and brain mitochondria, the underlying mechanism
      is still debated. Here, we present further arguments supporting our concept that
      MC acting on rat liver mitochondria suspended in KCl medium permeabilizes the
      inner membrane. Supplementation of the medium with cytochrome c and NAD(+)
      strongly enhanced the respiration of MC-treated mitochondria, thus partly
      preventing or reversing the inhibitory effect of MC on state 3 or uncoupled
      respiration. These results indicate that MC produced depletion of mitochondrial
      cytochrome c and NAD(+) , thus impairing mitochondrial respiration. In addition,
      NADH oxidation by alamethicin-permeabilized mitochondria supplemented with
      cytochrome c was insensitive to 200 MUm MC, arguing against direct impairment of
      respiratory chain complexes by MC. Finally, a surprising feature of MC was its
      accumulation or binding by intact rat liver mitochondria, but not by mitochondria
      permeabilized with alamethicin or disrupted by freezing and thawing. 

PMID- 24119168
TI  - The contribution of red blood cells to thrombin generation in sickle cell
      disease: meizothrombin generation on sickled red blood cells.

PMID- 24119169
TI  - The use of cardiac output monitoring to guide the administration of intravenous
      fluid during hyperthermic intraperitoneal chemotherapy.
AB  - AIM: The optimal strategy for intravenous (IV) fluid management during
      administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear.
      In this prospective study we describe the use of a LiDCOrapidTM (LiDCO,
      Cambridge, UK) cardiac output monitor to guide IV fluid management during
      cytoreductive surgery (CRS) with HIPEC. The aim of this study was to determine
      whether cardiac output monitoring will allow close maintenance of physiological
      parameters during the HIPEC phase. METHOD: Twenty-five patients who underwent CRS
      combined with HIPEC were included in the study. Intra-operative IV fluid boluses
      were titrated using parameters measured by the LiDCOrapidTM monitor. Stroke
      volume variation was maintained below 10% with fluid boluses and mean arterial
      pressure was maintained within 20% of the baseline figure with vasopressors.
      RESULTS: There was no significant change in heart rate and cardiac output. The
      systemic vascular resistance dropped from an average of 966 dyn.s/cm-5 to 797 dyn
      s/cm(5) at 60 min during the HIPEC phase (P = 0.62) despite an increase in the
      dose of phenylepherine. The average total volume of fluid given was 748 ml in the
      first 30 min and 630 ml in the second 30 min with an average urine output of 307
      and 445 ml, respectively. The change in lactate levels was not statistically or
      clinically significant. CONCLUSION: LiDCOrapidTM is an effective noninvasive tool
      for guiding fluid management in this population. It allows the anaesthesiologist
      to maintain tight control of essential physiological parameters during a phase of
      the procedure in which there is a risk of renal injury.

PMID- 24119170
TI  - Measuring up to speech intelligibility.
AB  - Improvement or maintenance of speech intelligibility is a central aim in a whole
      range of conditions in speech-language therapy, both developmental and acquired.
      Best clinical practice and pursuance of the evidence base for interventions would
      suggest measurement of intelligibility forms a vital role in clinical decision
      making and monitoring. However, what should be measured to gauge intelligibility
      and how this is achieved and relates to clinical planning continues to be a topic
      of debate. This review considers the strengths and weaknesses of selected
      clinical approaches to intelligibility assessment, stressing the importance of
      explanatory, diagnostic testing as both a more sensitive and a clinically
      informative method. The worth of this, and any approach, is predicated, though,
      on awareness and control of key design, elicitation, transcription and
      listening/listener variables to maximize validity and reliability of assessments.
      These are discussed. A distinction is drawn between signal-dependent and 
      independent factors in intelligibility evaluation. Discussion broaches how these
      different perspectives might be reconciled to deliver comprehensive insights into
      intelligibility levels and their clinical/educational significance. The paper
      ends with a call for wider implementation of best practice around intelligibility
      assessment. 

PMID- 24119171
TI  - The metabolic response of cultured tomato cells to low oxygen stress.
AB  - The storage of fruits and vegetables under a controlled atmosphere can induce low
      oxygen stress, which can lead to post-harvest losses through the induction of
      disorders such as core breakdown and browning. To gain better understanding of
      the metabolic response of plant organs to low oxygen, cultured tomato cells
      (Lycopersicum esculentum) were used as a model system to study the metabolic
      stress response to low oxygen (0 and 1 kPa O2). By adding 13C labelled glucose,
      changes in the levels of polar metabolites and their 13C label accumulation were
      quantified. Low oxygen stress altered the metabolite profile of tomato cells,
      with the accumulation of the intermediates of glycolysis in addition to increases
      in lactate and sugar alcohols. 13C label data showed reduced label accumulation
      in almost all metabolites except lactate and some sugar alcohols. The results
      showed that low oxygen stress in tomato cell culture activated fermentative
      metabolism and sugar alcohol synthesis while inhibiting the activity of the TCA
      cycle and the biosynthesis of metabolites whose precursors are derived from
      central metabolism, including fluxes to most organic acids, amino acids and
      sugars.

PMID- 24119172
TI  - A case of linear porokeratosis treated with photodynamic therapy with confocal
      microscopy surveillance.
AB  - Linear porokeratosis (LP) is a rare clinical porokeratosis variant, which
      typically presents at birth, but can also develop in adulthood. Differential
      diagnosis includes linear lichen planus, lichen striatus, linear verrucous
      epidermal nevus, incontinentia pigmenti and linear Darier's disease. An LP lesion
      has an increased risk of transformation into a squamous cell carcinoma or basal
      cell carcinoma. The treatment of LP is contradictory and disappointing in
      general. We present a case of a 16-year-old girl with multiple reddish-brown
      macules and depressions on the medial aspect of her right arm, localized from the
      palmar joint up to shoulder region in a linear pattern. We performed confocal
      microscopy (CLSM) of multiple lesions and a punch biopsy after receiving informed
      consent to confirm the diagnosis. After diagnosis confirmation, we performed
      Photodynamic therapy (PDT). Methyl aminolevulinate cream in a 160 mg/g
      concentration (Metvix crm) was applied under occlusion on the previously cleaned
      surface of every single lesion for 3 hours. The lesions were subsequently
      illuminated with a dose of 37 J/cm(2) (Aktilite, PhotoCure ASA, Norway). Two
      months after the first PDT treatment, the patient came for a third PDT session.
      Treatment follow-up was performed 6 months after the initial PDT session. A CLSM
      image proved an increase in the width of the stratum spinosum to 42-48 MUm, mild
      post-inflammatory changes were also present. Cosmetic and clinical response up to
      date at the time of last follow-up (1 year) was satisfactory. No progression was
      observed.

PMID- 24119173
TI  - Structure-function correlation of focal and diffuse temporal perifoveolar
      thinning in Alport syndrome.

PMID- 24119174
TI  - The relationship between exercise-induced muscle fatigue, arterial blood flow and
      muscle perfusion after 56 days local muscle unloading.
AB  - In the light of the dynamic nature of habitual plantar flexor activity, we
      utilized an incremental isokinetic exercise test (IIET) to assess the work
      related power deficit (WoRPD) as a measure for exercise-induced muscle fatigue
      before and after prolonged calf muscle unloading and in relation to arterial
      blood flow and muscle perfusion. Eleven male subjects (31 +/- 6 years) wore the
      HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual
      ambulation while greatly reducing plantar flexor activity and torque production.
      Endpoint measurements encompassed arterial blood flow, measured in the femoral
      artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by
      near-infrared spectroscopy, lactate concentrations determined in capillary blood
      and muscle activity using soleus muscle surface electromyography. Furthermore,
      soleus muscle biopsies were taken to investigate morphological muscle changes.
      After the intervention, maximal isokinetic torque was reduced by 23.4 +/- 8.2%
      (P<0.001) and soleus fibre size was reduced by 8.5 +/- 13% (P = 0.016). However,
      WoRPD remained unaffected as indicated by an unchanged loss of relative plantar
      flexor power between pre- and postexperiments (P = 0.88). Blood flow, tissue
      oxygenation, lactate concentrations and EMG median frequency kinematics during
      the exercise test were comparable before and after the intervention, whereas the
      increase of RMS in response to IIET was less following the intervention (P =
      0.03). In conclusion, following submaximal isokinetic muscle work exercise
      induced muscle fatigue is unaffected after prolonged local muscle unloading. The
      observation that arterial blood flow was maintained may underlie the unchanged
      fatigability. 

PMID- 24119175
TI  - External validation of preoperative and postoperative nomograms for prediction of
      cancer-specific survival, overall survival and recurrence after robot-assisted
      radical cystectomy for urothelial carcinoma of the bladder.
AB  - OBJECTIVE: To externally validate currently available bladder cancer nomograms
      for prediction of all-cause survival (ACS), cancer-specific survival (CSS), other
      cause mortality (OCM) and progression-free survival (PFS). PATIENTS AND METHODS:
      Retrospective analysis of a prospectively maintained database of 282 patients who
      underwent robot-assisted radical cystectomy (RARC) at a single institution was
      performed. The Bladder Cancer Research Consortium (BCRC), International Bladder
      Cancer Nomogram Consortium (IBCNC) and Lughezzani nomograms were used for
      external validation, and evaluation for accuracy at predicting oncological
      outcomes. The 2- and 5-year oncological outcomes were compared, and nomogram
      performance was evaluated through measurement of the concordance (c-index)
      between nomogram-derived predicted oncological outcomes and observed oncological
      outcomes. RESULTS: The median (range) patient age was 70 (36-90) years. At a mean
      follow-up of 20 months, local or distant disease recurrence developed in 30% of
      patients. With an overall mortality rate of 33%, 17% died from bladder cancer.
      The actuarial 2- and 5-year PFS after RARC was 62% (95% confidence interval [CI]
      54-68) and 55% (95% CI 46-63), respectively. The actuarial 2- and 5-year ACS was
      66% (95% CI 59-72) and 47% (95% CI 37-55), respectively, and the 2- and 5-year
      CSS was 81% (95% CI 74-86) and 67% (95% CI 57-76), respectively. The PFS c-index
      for IBCNC was 0.70 at 5 years, and for BCRC was 0.77 at both the 2 and 5 years.
      The accuracy of ACS and CSS prediction was evaluated using the BCRC and
      Lughezzani nomograms. Using the BCRC nomogram, c-indices of for 2- and 5-year ACS
      were each 0.73 and c-indices for 2- and 5-year CSS were 0.70 each. The
      performance of Lughezzani nomogram for 5-year ACS, cancer-specific mortality and
      OCM were 0.73, 0.72 and 0.40, respectively. The BCRC nomogram prediction of
      advanced pathological stage and lymph node metastasis was modest, with c-indices
      of 0.66 and 0.61, respectively. CONCLUSIONS: Bladder cancer nomograms available
      from the current open RC literature adequately predict ACS, CSS and PFS after
      RARC. However, prediction of advanced tumour stage and lymph node metastasis was
      modest and the Lughezzani nomogram failed to predict OCM.

PMID- 24119177
TI  - Habitat area and climate stability determine geographical variation in plant
      species range sizes.
AB  - Despite being a fundamental aspect of biodiversity, little is known about what
      controls species range sizes. This is especially the case for hyperdiverse
      organisms such as plants. We use the largest botanical data set assembled to date
      to quantify geographical variation in range size for ~ 85 000 plant species
      across the New World. We assess prominent hypothesised range-size controls,
      finding that plant range sizes are codetermined by habitat area and long- and
      short-term climate stability. Strong short- and long-term climate instability in
      large parts of North America, including past glaciations, are associated with
      broad-ranged species. In contrast, small habitat areas and a stable climate
      characterise areas with high concentrations of small-ranged species in the Andes,
      Central America and the Brazilian Atlantic Rainforest region. The joint roles of
      area and climate stability strengthen concerns over the potential effects of
      future climate change and habitat loss on biodiversity. 

PMID- 24119178
TI  - Concordance between patient and physician assessment of the magnitude of
      Peyronie's disease curvature.
AB  - INTRODUCTION: The magnitude of penile deformity is a critically important factor
      in Peyronie's disease, as it is associated with increased difficulty in
      penetrative sexual intercourse and in turn with negative psychosocial
      consequences. Deformity magnitude also influences treatment choice when surgical
      correction is indicated. AIM: To determine the concordance between patient and
      physician assessment of magnitude of penile curvature in men with Peyronie's
      disease. METHODS: Patient assessment of curvature was obtained at initial
      interview. Physician assessment was performed using intracavernosal injection
      assisted erection using a goniometer applied during excellent penile rigidity.
      MAIN OUTCOME MEASURES: Patient and physician assessments of penile curvature.
      RESULTS: The sample consisted of 192 men with a mean age of 54 +/- 12 years old.
      Mean curvature on patient and physician assessment was 33 +/- 17 and 36 +/- 18
      degrees, respectively. Only 49% of patients (94) correctly assessed their
      curvature, whereas 35% underestimated and 16% overestimated it. CONCLUSIONS: Only
      half of PD patients accurately assess their penile curvature, with more than
      twice as many patients underestimating it than overestimating it. These data
      suggest that patient self-reporting of penile curvature should not be used as a
      clinical marker or end point in Peyronie's disease trials.

PMID- 24119179
TI  - Assessment of glycan interactions of clinical and avian isolates of Campylobacter
      jejuni.
AB  - BACKGROUND: Campylobacter jejuni strain 11168 was demonstrated to have a broad
      specificity for eukaryotic surface glycosylation using glycan array analysis. The
      initial screen indicated that sialic acid and mannose are important binding
      partners after environmental stress, while galactose and fucose structures are
      likely to be involved in persistent infection. RESULTS: In this broader study,
      five additional human/clinical isolates and six chicken isolates were fully
      assessed to determine their glycan binding capacity using an extended glycan
      array. C. jejuni 11168 was rescreened here due to the presence of
      glycoaminoglycan (GAG) and other structures that were not available on our
      previous glycan array. The current array analysis of additional C. jejuni strains
      confirmed the growth condition dependent differences in glycan binding that was
      previously observed for C. jejuni 11168. We noted strain to strain variations,
      particularly for the human isolates C. jejuni 520 and 81116 and the chicken
      isolate C. jejuni 331, with the majority of differences observed in galactose,
      mannose and GAG binding. Chicken isolates were found to bind to a broader range
      of glycans compared to the human isolates, recognising branched mannose and
      carageenan (red seaweed) glycans. Glycan array data was confirmed using cell
      based lectin inhibition assays with the fucose (UEA-I) and mannose (ConA) binding
      lectins. CONCLUSIONS: This study confirms that all C. jejuni strains tested bind
      to a broad range of glycans, with the majority of strains (all except 81116)
      altering recognition of sialic acid and mannose after environmental stress.
      Galactose and fucose structures were bound best by all strains when C. jejuni was
      grown under host like conditions confirming the likelihood of these structures
      being involved in persistent infection.

PMID- 24119180
TI  - Monitoring lithium therapy: the impact of a quality improvement programme in the
      UK.
AB  - OBJECTIVES: The study was designed to test an audit-based quality improvement
      programme (QIP) addressing lithium prescribing and monitoring in UK mental health
      services. METHODS: A baseline clinical audit was conducted against the following
      standards: (i) measurement of renal and thyroid function before initiating
      treatment with lithium and (ii) recommended monitoring of serum lithium and renal
      and thyroid function during maintenance treatment. A re-audit was conducted at 18
      months and a supplementary audit at three years. RESULTS: Data were submitted for
      patients at baseline (n = 3,373), re-audit (n = 3,647), and supplementary audit
      (n = 5,683), 57% of whom had bipolar disorder. The baseline findings prompted a
      patient safety alert issued by the National Patient Safety Agency. By
      supplementary audit, the proportion of patients having four serum lithium tests
      over the previous year had increased from 30% at baseline to 48%, and the
      respective proportions that had two tests of renal function from 55% to 70% and
      thyroid function from 49% to 66%. Elderly patients and those prescribed a drug
      known to interact with lithium were not more likely to be monitored in line with
      the audit standards. Between baseline and supplementary audit, the proportion of
      patients with a diagnosis of bipolar disorder prescribed an antidepressant
      increased from 36% to 41%. CONCLUSIONS: Improvements in biochemical monitoring of
      lithium treatment were achieved over time with participation in a QIP that
      included benchmarking of performance against clinical standards and customized
      change interventions. Nevertheless, gaps remain between the standard and current
      practice. Antidepressants are frequently prescribed in patients with bipolar
      disorder despite a paucity of evidence supporting their efficacy.

PMID- 24119181
TI  - Squalene epoxidase as a target for manipulation of squalene levels in the yeast
      Saccharomyces cerevisiae.
AB  - Squalene is a valuable natural substance with several biotechnological
      applications. In the yeast Saccharomyces cerevisiae, it is produced in the
      isoprenoid pathway as the first precursor dedicated to ergosterol biosynthesis.
      The aim of this study was to explore the potential of squalene epoxidase encoded
      by the ERG1 gene as the target for manipulating squalene levels in yeast. Highest
      squalene levels (over 1000 MUg squalene per 10(9)  cells) were induced by
      specific point mutations in ERG1 gene that reduced activity of squalene epoxidase
      and caused hypersensitivity to terbinafine. This accumulation of squalene in erg1
      mutants did not significantly disturb their growth. Treatment with squalene
      epoxidase inhibitor terbinafine revealed a limit in squalene accumulation at 700
      MUg squalene per 10(9)  cells which was associated with pronounced growth
      defects. Inhibition of squalene epoxidase activity by anaerobiosis or heme
      deficiency resulted in relatively low squalene levels. These levels were
      significantly increased by ergosterol depletion in anaerobic cells which
      indicated feedback inhibition of squalene production by ergosterol. Accumulation
      of squalene in erg1 mutants and terbinafine-treated cells were associated with
      increased cellular content and aggregation of lipid droplets. Our results prove
      that targeted genetic manipulation of the ERG1 gene is a promising tool for
      increasing squalene production in yeast. 

PMID- 24119182
TI  - The effect of low-dose carvedilol, nebivolol, and metoprolol on central arterial
      pressure and its determinants: a randomized clinical trial.
AB  - In this prospective, open-label, randomized, controlled clinical trial the
      effects of low-dose carvedilol, nebivolol, and metoprolol on central arterial
      pressure and augmentation index (AIx) and its heart rate-corrected value (AIx@75)
      were assessed. The authors randomized 75 hypertensive patients (18-70 years) to
      carvedilol 12.5/25 mg, metoprolol 50/100 mg, or nebivolol 2.5/5 mg daily and
      followed them up for 3 months. Central arterial pressure and AIx were measured
      with applanation tonometry at baseline and at the end of follow-up. Analyses were
      restricted to 60 completers. Central systolic pressure decreased equally in all 3
      treatment arms. AIx remained unchanged, while AIx@75 decreased significantly by
      5.4%+/-2.5% in the nebivolol group. According to general linear models,
      individual change in heart rate was a strong predictor of change in AIx in the
      carvedilol group (r(2) =0.23, P=.03) although no similar association was found in
      the nebivolol group (r(2) =0.09). The impact of beta-blockers with vasodilator
      effects on pressure augmentation seems to be different with nebivolol having the
      largest potential of decreasing AIx@75. While AIx changes associated with
      carvedilol treatment are strongly driven by heart rate changes, those associated
      with nebivolol treatment seem to be the result of other mechanisms. 

PMID- 24119183
TI  - Realising the value of plant molecular pharming to benefit the poor in developing
      countries and emerging economies.
AB  - Molecular Pharming, the production of recombinant pharmaceuticals through plant
      biotechnology, has the potential to transform the biologics sector of the
      pharmaceutical industry. More fascinating however, is how it might be used to
      improve access to modern medicines, and improve health of the poor in developing
      countries and emerging economies. Although improving global health through
      molecular pharming has been discussed for at least two decades, little progress
      has actually been made. In this manuscript, a four point plan is described to
      maximise the opportunity for molecular pharming to provide solutions. These are
      (i) to identify and prioritise important drug targets that are relevant to the
      poor; (ii) to support research and development partners in low to middle income
      countries to develop local expertise, transfer technology and build capacity;
      (iii) to increase collaboration between regulatory bodies to enable national
      regulatory frameworks to be developed in low to middle income countries; and (iv)
      to promote intellectual property management approaches that include socially
      responsible licensing. An existing case study is described to illustrate how this
      might be achieved.

PMID- 24119184
TI  - A new multiplex SNP genotyping assay for detecting hybridization and
      introgression between the M and S molecular forms of Anopheles gambiae.
AB  - The M and S forms of Anopheles gambiae have been the subject of intense study,
      but are morphologically indistinguishable and can only be identified using
      molecular techniques. PCR-based assays to distinguish the two forms have been
      designed and applied widely. However, the application of these assays towards
      identifying hybrids between the two forms, and backcrossed hybrids in particular,
      has been problematic as the currently available diagnostic assays are based on
      single locus and/or are located within a multicopy gene. Here, we present an
      alternative genotyping method for detecting hybridization and introgression
      between M and S molecular forms based on a multilocus panel of single-nucleotide
      polymorphisms (SNPs) fixed between the M and S forms. The panel of SNPs employed
      is located in so-called islands of divergence leading us to describe this method
      as the 'Divergence Island SNP' (DIS) assay. We show this multilocus SNP
      genotyping approach can robustly and accurately detect F1 hybrids as well as
      backcrossed individuals. 

PMID- 24119185
TI  - Cellular response to micropatterned growth promoting and inhibitory substrates.
AB  - BACKGROUND: Normal development and the response to injury both require cell
      growth, migration and morphological remodeling, guided by a complex local
      landscape of permissive and inhibitory cues. A standard approach for studying by
      such cues is to culture cells on uniform substrates containing known
      concentrations of these molecules, however this method fails to represent the
      molecular complexity of the natural growth environment. RESULTS: To mimic the
      local complexity of environmental conditions in vitro, we used a contact
      micropatterning technique to examine cell growth and differentiation on patterned
      substrates printed with the commonly studied growth permissive and inhibitory
      substrates, poly-L-lysine (PLL) and myelin, respectively. We show that
      micropatterning of PLL can be used to direct adherence and axonal outgrowth of
      hippocampal and cortical neurons as well as other cells with diverse morphologies
      like Oli-neu oligodendrocyte progenitor cell lines and fibroblast-like COS7 cells
      in culture. Surprisingly, COS7 cells exhibited a preference for low concentration
      (1 pg/mL) PLL zones over adjacent zones printed with high concentrations (1
      mg/mL). We demonstrate that micropatterning is also useful for studying factors
      that inhibit growth as it can direct cells to grow along straight lines that are
      easy to quantify. Furthermore, we provide the first demonstration of microcontact
      printing of myelin-associated proteins and show that they impair process
      outgrowth from Oli-neu oligodendrocyte precursor cells. CONCLUSION: We conclude
      that microcontact printing is an efficient and reproducible method for patterning
      proteins and brain-derived myelin on glass surfaces in order to study the effects
      of the microenvironment on cell growth and morphogenesis.

PMID- 24119186
TI  - Osteopoikilosis and ankylosing spondylitis: a rare coexistence and good response
      to TNF blocker adalimumab.

PMID- 24119187
TI  - Adenosine increases LPS-induced nuclear factor kappa B activation in smooth
      muscle cells via an intracellular mechanism and modulates it via actions on
      adenosine receptors.
AB  - AIM: In inflamed and damaged cardiovascular tissues, local extracellular
      adenosine concentrations increase coincidentally with activation of the
      transcription factor nuclear factor kappa B (NFkappaB). To investigate whether
      adenosine influences NFkappaB activation in vascular smooth muscle cells (VSMCs)
      and, if so, to examine the role of its receptors. METHODS: VSMCs were isolated
      from NFkappaB-luciferase reporter mice, cultured and then treated by
      lipopolysaccharide (LPS) to activate NFkappaB signalling. Adenosine, adenosine
      receptor agonists and antagonists, adenosine deaminase and uptake inhibitors were
      used together with LPS to evaluate the role of adenosine and its receptors on
      NFkappaB activation, which was assessed by luciferase activity and NFkappaB
      target gene expression. RESULTS: Adenosine potentiated LPS-induced NFkappaB
      activation. This was dependent on adenosine uptake and enhanced by an adenosine
      deaminase inhibitor, suggesting that intracellular adenosine plays an important
      role. Non-selective adenosine receptor agonists (2Cl-Ado and NECA) inhibited
      NFkappaB activation induced by LPS. Selective A1 or A2A antagonist given alone
      could not completely antagonize the NECA effect, indicating that the inhibitory
      effect was due to multiple adenosine receptors. The activation of the A3 receptor
      further increased LPS-induced NFkappaB activation. CONCLUSIONS: Adenosine
      increases LPS-induced nuclear factor kappa B activation in smooth muscle cells
      via an intracellular mechanism and decreases it via actions on A1 and A2A
      receptors. These results provide novel insights into the role of adenosine as a
      regulator of inflammation-induced NFkappaB activation.

PMID- 24119188
TI  - Inhibition of alphavbeta6 promotes acute renal allograft rejection in nonhuman
      primates.
AB  - The integrin alphavbeta6 activates latent transforming growth factor-beta (TGF
      beta) within the kidney and may be a target for the prevention of chronic
      allograft fibrosis after kidney transplantation. However, TGF-beta also has known
      immunosuppressive properties that are exploited by calcineurin inhibitors (CNIs);
      thus, the net benefit of alphavbeta6 inhibition remains undetermined. To assess
      the acute impact of interference with alphavbeta6 on acute rejection, we tested a
      humanized alphavbeta6-specific monoclonal antibody (STX-100) in a randomized,
      double-blinded, placebo-controlled nonhuman primate renal transplantation study
      to evaluate whether alphavbeta6 blockade alters the risk of acute rejection
      during CNI-based immunosuppression. Rhesus monkeys underwent renal
      allotransplantation under standard CNI-based maintenance immunosuppression; 10
      biopsy-confirmed rejection-free animals were randomized to receive weekly STX-100
      or placebo. Animals treated with STX-100 experienced significantly decreased
      rejection-free survival compared to placebo animals (p = 0.049).
      Immunohistochemical analysis confirmed alphavbeta6 ligand presence, and
      alphavbeta6 staining intensity was lower in STX-100-treated animals (p = 0.055),
      indicating an apparent blockade effect of STX-100. LAP, LTBP-1 and TGF-beta were
      all decreased in animals that rejected on STX-100 compared to those that rejected
      on standard immunosuppression alone, suggesting a relevant effect of alphavbeta6
      blockade on local TGF-beta. These data caution against the use of alphavbeta6
      blockade to achieve TGF-beta inhibition in kidney transplantation.

PMID- 24119190
TI  - Ulcerated necrobiosis lipoidica as a rare cause for chronic leg ulcers: case
      report series of ten patients.
AB  - Necrobiosis lipoidica is a rare granulomatous disorder of the skin. In up to 30%
      of the affected patients it can lead to ulcerations, which can impair the quality
      of life and are also very difficult to treat. Its pathogenesis is not fully
      understood. Only few studies focussing on necrobiosis lipoidica can be found, but
      none of them focus on ulcerated necrobiosis lipoidica. Therefore, we collected
      demographic data and comorbidities and assessed treatment options for patients
      with ulcerated necrobiosis lipoidica. Data of patients who were treated in the
      wound care centre of the University Hospital of Essen for ulcerated necrobiosis
      lipoidica over the past 10 years were retrospectively analysed. Hence, data of
      altogether ten patients (nine women and one man) with ulcerated necrobiosis
      lipoidica were collected. Of these, 70% of the patients had diabetes mellitus of
      which 30% had type I diabetes and 40% had type II diabetes; 60% of the patients
      suffered from arterial hypertension, obesity and hypercholesterolaemia; 40% of
      the patients suffered from psychiatric disorders such as depression and
      borderline disorder. Our clinical data demonstrate an association of ulcerated
      necrobiosis lipoidica and aspects of metabolic syndrome. This leads to a
      conclusion that ulcerating necrobiosis lipoidica can be seen as part of a
      generalised inflammatory reaction similar to the inflammatory reaction already
      known in the pathophysiology of rheumatoid diseases or psoriasis. In patients
      with clinical atypical painful ulcerations, necrobiosis lipoidica should be
      considered as a possible differential diagnosis. Therapists should be aware of
      associated aspects in patients with ulcerated necrobiosis lipoidica who besides
      diabetes often suffer from other aspects of a metabolic syndrome with increased
      cardiovascular risk factors. Therefore, these related comorbidities should also
      be diagnosed and treated. 

PMID- 24119189
TI  - Aeromonas salmonicida subsp. salmonicida in the light of its type-three secretion
      system.
AB  - Aeromonas salmonicida subsp. salmonicida is an important pathogen in salmonid
      aquaculture and is responsible for the typical furunculosis. The type-three
      secretion system (T3SS) is a major virulence system. In this work, we review
      structure and function of this highly sophisticated nanosyringe in A.
      salmonicida. Based on the literature as well as personal experimental
      observations, we document the genetic (re)organization, expression regulation,
      anatomy, putative functional origin and roles in the infectious process of this
      T3SS. We propose a model of pathogenesis where A. salmonicida induces a temporary
      immunosuppression state in fish in order to acquire free access to host tissues.
      Finally, we highlight putative important therapeutic and vaccine strategies to
      prevent furunculosis of salmonid fish.

PMID- 24119191
TI  - SiiA and SiiB are novel type I secretion system subunits controlling SPI4
      mediated adhesion of Salmonella enterica.
AB  - The giant non-fimbrial adhesin SiiE is essential to establish intimate contact
      between Salmonella enterica and the apical surface of polarized epithelial cells.
      SiiE is secreted by a type I secretion system (T1SS) encoded by Salmonella
      Pathogenicity Island 4 (SPI4). We identified SiiA and SiiB as two regulatory
      proteins encoded by SPI4. Mutant strains in siiA or siiB still secrete SiiE, but
      are highly reduced in adhesion to, and invasion of polarized cells. SiiA and SiiB
      are inner membrane proteins with one and three transmembrane (TM) helices
      respectively. TM2 and TM3 of SiiB are similar to members of the ExbB/TolQ family,
      while the TM of SiiA is similar to MotB and a conserved aspartate residue in this
      TM is essential for SPI4-encoded T1SS function. Co-immunoprecipitation, bacterial
      two-hybrid and FRET demonstrate homo- and heterotypic protein interactions for
      SiiA and SiiB. SiiB, but not SiiA also interacts with the SPI4-T1SS ATPase SiiF.
      The integrity of the Walker A box in SiiF was required for SiiB-SiiF
      interactionand SiiF dimer formation. Based on these data, we describe SiiA and
      SiiB as new, exclusively virulence-associated members of the Mot/Exb/Tol family
      of membrane proteins. Both proteins are involved in a novel mechanism of
      controlling SPI4-T1SS-dependent adhesion, most likely by formation of a proton
      conducting channel. 

PMID- 24119193
TI  - A relationship between tube length and intra-ocular pressure after glaucoma
      drainage implant surgery cannot be explained by Poiseuille's law - author's
      reply.

PMID- 24119192
TI  - Tissue oxygenation, strength and lactate response to different blood flow
      restrictive pressures.
AB  - This study aimed to determine whether changes in initial restrictive pressures
      (IRP, tightness of the cuff before inflation with air) affect tissue oxygenation,
      lactate production and leg strength before, during and after knee extension
      exercises. The cuff was positioned on the right thigh, and the IRP of either 40
      45 or 60-65 mmHg were applied randomly prior to inflating the cuff to the final
      restrictive pressure (the pressure reached after inflating the cuff with air).
      Subjects performed four sets (30, 15, 15 and 15 reps) of isotonic knee extensions
      with 1-min rest between sets. Tissue oxygenation and blood lactate levels were
      assessed prior to, during and after exercise, and leg strength was assessed pre-
      and postexercise. There were significant condition by time interactions (P<0.01)
      and main effects for both condition (P<0.01) and time (P<0.01) for tissue
      oxygenation, deoxyhaemoglobin, total haemoglobin. Significant main effects were
      detected for both condition (P<0.01) and time (P<0.01) for leg strength values.
      There was only a significant time main effect for lactate concentrations. This
      study is the first to show that a higher IRP had a significant impact on percent
      tissue oxygenation, leg strength and deoxygenated haemoglobin accumulation during
      exercise.

PMID- 24119194
TI  - Posttraumatic irritant contact dermatitis--an underdiagnosed entity?

PMID- 24119195
TI  - Kimura disease: rare cause of a slowly progressive orbital mass.

PMID- 24119196
TI  - Mini-probe ultrasonography for the staging of colon cancer: a systematic review
      and meta-analysis.
AB  - AIM: With an increasing array of treatment modalities available for colon cancer,
      it is increasingly important to stage tumours accurately to allocate the
      appropriate management. This study evaluated the accuracy of mini-probe
      endoscopic ultrasound (EUS) in assigning clinical stage to colon cancer. METHOD:
      An electronic search was performed in January 2013 using the Embase, MEDLINE and
      Cochrane databases. This was supplemented by a hand search of published abstracts
      from scientific meetings. Trials evaluating the accuracy of the mini-probe EUS
      compared with histopathological grade in determining the clinical stage of colon
      cancer were included in this pooled analysis. The main outcome measures included
      accuracy, sensitivity and specificity for T and N staging. RESULTS: Ten studies
      were identified which compared the mini-probe EUS staging of 642 colon or rectal
      cancers with the histopathological specimen. The pooled sensitivity and
      specificity for staging were 0.91 and 0.98 for T1 tumours, 0.78 and 0.94 for T2
      tumours, 0.97 and 0.90 for T3/T4 tumours and 0.63 and 0.82 for nodal staging.
      Eight per cent of T1/T2 tumours were upstaged to T3/T4 tumours and 5% of T3/T4
      tumours were downstaged. CONCLUSION: Mini-probe EUS is highly effective for
      assigning clinical stage in colon cancer and in identifying patients who may be
      suitable for nonsurgical treatment including neoadjuvant chemotherapy or
      endoscopic resection.

PMID- 24119197
TI  - Matrix metalloproteinase-10 expression is induced during hepatic injury and plays
      a fundamental role in liver tissue repair.
AB  - BACKGROUND & AIMS: Upon tissue injury, the liver mounts a potent reparative and
      regenerative response. A role for proteases, including serine and matrix
      metalloproteinases (MMPs), in this process is increasingly recognized. We have
      evaluated the expression and function of MMP10 (stromelysin-2) in liver wound
      healing and regeneration. METHODS: The hepatic expression of MMP10 was examined
      in two murine models: liver regeneration after two-thirds partial hepatectomy
      (PH) and bile duct ligation (BDL). MMP10 was detected in liver tissues by qPCR,
      western blotting and immunohistochemistry. The effect of growth factors and toll
      like receptor 4 (TLR4) agonists on MMP10 expression was studied in cultured
      parenchymal and biliary epithelial cells and macrophages respectively. The role
      of MMP10 was evaluated by comparing the response of Mmp10+/+ and Mmp10-/- mice to
      PH and BDL. The intrahepatic turnover of the extracellular matrix proteins fibrin
      (ogen) and fibronectin was examined. RESULTS: MMP10 mRNA was readily induced
      after PH and BDL. MMP10 protein was detected in hepatocytes, cholangiocytes and
      macrophages. In cultured liver epithelial cells, MMP10 expression was additively
      induced by transforming growth factor-beta and epidermal growth factor receptor
      ligands. TLR4 ligands also stimulated MMP10 expression in macrophages. Lack of
      MMP10 resulted in increased liver injury upon PH and BDL. Resolution of necrotic
      areas was impaired, and Mmp10-/- mice showed increased fibrogenesis and defective
      turnover of fibrin (ogen) and fibronectin. CONCLUSIONS: MMP10 expression is
      induced during mouse liver injury and participates in the hepatic wound healing
      response. The profibrinolytic activity of MMP10 may be essential in this novel
      hepatoprotective role.

PMID- 24119198
TI  - Discovery of synthetic Leishmania inhibitors by screening of a 2
      arylbenzothiophene library.
AB  - Tamoxifen has been shown to be active in vitro against Leishmania and effective
      in the treatment for leishmaniasis in murine models. Through the screening of a
      compound library of estrogen receptor modulator analogs, we identified the major
      characteristics required for antileishmanial activity. To overcome the
      difficulties presented by tamoxifen's propensity for E/Z isomerization, we used
      the 2-arylbenzothiophene compound BTP as a more stable alternative. Directed
      screening of a small compound library based on BTP led to active compounds
      against Leishmania. Subsequent structure-activity data for the synthetic 2
      arylbenzothiophenes evaluated in this study indicate that optimal antileishmanial
      potency is dependent on the presence of two basic side chains. In addition, the
      primary structural features required for estrogen receptor binding, the phenols,
      are not required for inhibiting parasitic growth. Significantly, the most active
      antileishmanial benzothiophenes lack the pharmacophore for estrogen receptor
      activity and therefore address potential concerns about the undesirable effects
      of using selective estrogen receptor modulators in women and children with
      leishmaniasis. Three compounds selected from the screening have shown consistent
      activity against all species and stages of Leishmania in vitro although
      improvements in selectivity are needed. These compounds represent viable starting
      points for further optimization as antileishmanial agents. 

PMID- 24119199
TI  - The protective role of coenzyme Q10 in renal injury associated with
      extracorporeal shockwave lithotripsy: a randomised, placebo-controlled clinical
      trial.
AB  - OBJECTIVE: To determine the efficacy of coenzyme Q10 (CoQ10) in preventing renal
      injury in patients with lithiasis undergoing extracorporeal shockwave lithotripsy
      (ESWL). PATIENTS AND METHODS: Prospective, randomised, double-blind, placebo
      controlled clinical trial of 100 patients with renal lithiasis who were treated
      with ESWL. The patients were distributed randomly into two groups receiving
      either placebo or CoQ10 (200 mg/day), a powerful antioxidant with vasoactive
      properties, orally administered during the week before ESWL and for 1 week after.
      Renal dysfunction markers, vasoactive hormones, oxidative stress, plasma levels
      of several interleukins and vascular resistance index (VRI) using Doppler
      ultrasound were evaluated the week before ESWL, 2 h before ESWL and at 2 h, 24 h
      and 7 days after ESWL. RESULTS: There was a significant increase in glomerular
      filtration (P = 0.013), as well as a decrease in the albumin/creatinine ratio and
      the beta2 -microglobulin level (P = 0.02) after 1 week of treatment in the CoQ10
      group. These changes were maintained at the follow-up after ESWL. The
      administration of CoQ10 was associated with improvement in vasoactive hormone
      parameters, VRI and interleukin levels. These improvements were maintained until
      the end of the follow-up period. However, the administration of CoQ10 was not
      associated with significant changes in the oxidative stress parameters.
      CONCLUSION: Our results indicate that CoQ10 administration improves renal
      function and vasoactive and inflammation parameter values, allowing for
      preconditioning before the tissue insult caused by ESWL.

PMID- 24119200
TI  - A three-component signalling system fine-tunes expression kinetics of HPPK
      responsible for folate synthesis by positive feedback loop during stress response
      of Xanthomonas campestris.
AB  - During adaptation to environments, bacteria employ two-component signal
      transduction systems, which contain histidine kinases and response regulators, to
      sense and respond to exogenous and cellular stimuli in an accurate spatio
      temporal manner. Although the protein phosphorylation process between histidine
      kinase and response regulator has been well documented, the molecular mechanism
      fine-tuning phosphorylation levels of response regulators is comparatively less
      studied. Here we combined genetic and biochemical approaches to reveal that a
      hybrid histidine kinase, SreS, is involved in the SreK-SreR phosphotransfer
      process to control salt stress response in the bacterium Xanthomonas campestris.
      The N-terminal receiver domain of SreS acts as a phosphate sink by competing with
      the response regulator SreR to accept the phosphoryl group from the latter's
      cognate histidine kinase SreK. This regulatory process is critical for bacterial
      survival because the dephosphorylated SreR protein participates in activating one
      of the tandem promoters (P2) at the 5' end of the sreK-sreR-sreS-hppK operon, and
      then modulates a transcriptional surge of the stress-responsive gene hppK, which
      is required for folic acid synthesis. Therefore, our study dissects the
      biochemical process of a positive feedback loop in which a 'three-component'
      signalling system fine-tunes expression kinetics of downstream genes. 

PMID- 24119201
TI  - Phosphorylation pattern of Rubisco activase in Arabidopsis leaves.
AB  - Rubisco activase (RCA) is an ancillary photosynthetic protein essential for
      Rubisco activity. Some data suggest that post-translational modifications (such
      as reduction of disulphide bridges) are involved in the regulation of RCA
      activity. However, despite the key role of protein phosphorylation in general
      metabolic regulation, RCA phosphorylation has not been well characterised. We
      took advantage of phosphoproteomics and gas exchange analyses with instant
      sampling adapted to Arabidopsis rosettes to examine the occurrence and variations
      of phosphopeptides associated with RCA in different photosynthetic contexts (CO2
      mole fraction, light and dark). We detected two phosphopeptides from RCA
      corresponding to residues Thr 78 and Ser 172, and show that the former is
      considerably more phosphorylated in the dark than in the light, while the latter
      show no light/dark pattern. The CO2 mole fraction did not influence
      phosphorylation of either residue. Phosphorylation thus appears to be a potential
      mechanism associated with RCA dark inactivation, when Rubisco-catalysed
      carboxylation is arrested. Since Thr 78 and Ser 172 are located in the N and
      Walker domains of the protein, respectively, the involvement of phosphorylation
      in protein-protein interaction and catalysis is likely.

PMID- 24119202
TI  - Switching hemodialysis patients from sevelamer hydrochloride to bixalomer: a
      single-center, non-randomized analysis of efficacy and effects on
      gastrointestinal symptoms and metabolic acidosis.
AB  - BACKGROUND: Bixalomer (BXL) was developed to improve gastrointestinal symptoms
      and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis
      patients. We prospectively evaluated the safety and effectiveness of switching
      maintenance dialysis patients from sevelamer hydrochloride to BXL. METHODS:
      Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1
      dose) from July to October 2012, whereas 84 randomly selected patients not
      treated with sevelamer hydrochloride were enrolled as a control group. The
      primary endpoint was improvement of gastrointestinal symptoms; secondary
      endpoints included improvement in metabolic acidosis, changes in blood
      biochemistry, and safety 12 weeks after the switch. We also surveyed patient
      satisfaction with switching to BXL 12 weeks after the switch. RESULTS: Before
      switching, symptoms of epigastric fullness were significantly worse in the switch
      than in the control group. Twelve weeks after the switch, reflux, epigastric
      fullness, and constipation had improved significantly in the switch group. Other
      factors, including stomach ache, diarrhea, and form of stool, did not change
      significantly. Blood gas analysis showed that metabolic acidosis was
      significantly improved by switching. Four patients (14%) experienced grade 1
      adverse events, all of which improved immediately after stopping BXL. Major
      adverse events were diarrhea and abdominal discomfort. Mean satisfaction score
      was 3.1 +/- 0.7, with 64% of patients reporting they were "neither satisfied nor
      dissatisfied" after switching. CONCLUSIONS: A switch from sevelamer hydrochloride
      to BXL improved symptoms of reflux, epigastric fullness, constipation, and
      metabolic acidosis in hemodialysis patients. TRIAL REGISTRATION: The study was
      registered as Clinical trial: (UMIN000011150).

PMID- 24119203
TI  - Accessing health services through the back door: a qualitative interview study
      investigating reasons why people participate in health research in Canada.
AB  - BACKGROUND: Although there is extensive information about why people participate
      in clinical trials, studies are largely based on quantitative evidence and
      typically focus on single conditions. Over the last decade investigations into
      why people volunteer for health research have become increasingly prominent
      across diverse research settings, offering variable based explanations of
      participation patterns driven primarily by recruitment concerns. Therapeutic
      misconception and altruism have emerged as predominant themes in this literature
      on motivations to participate in health research. This paper contributes to more
      recent qualitative approaches to understanding how and why people come to
      participate in various types of health research. We focus on the experience of
      participating and the meanings research participation has for people within the
      context of their lives and their health and illness biographies. METHODS: This is
      a qualitative exploratory study informed by grounded theory strategies. Thirty
      nine participants recruited in British Columbia and Manitoba, Canada, who had
      taken part in a diverse range of health research studies participated in semi
      structured interviews. Participants described their experiences of health
      research participation including motivations for volunteering. Interviews were
      recorded, transcribed, and analyzed using constant comparisons. Coding and data
      management was supported by Nvivo-7. RESULTS: A predominant theme to emerge was
      'participation in health research to access health services.' Participants
      described research as ways of accessing: (1) Medications that offered (hope of)
      relief; (2) better care; (3) technologies for monitoring health or illness.
      Participants perceived standard medical care to be a "trial and error" process
      akin to research, which further blurred the boundaries between research and
      treatment. CONCLUSIONS: Our findings have implications for recruitment, informed
      consent, and the dichotomizing of medical/health procedures as either research or
      treatment. Those with low health status may be more vulnerable to potential
      coercion, suggesting the need for a more cautious approach to obtaining consent.
      Our findings also indicate the need for boundary work in order to better
      differentiate treatment and research. It is important however to acknowledge a
      categorical ambiguity; it is not always the case that people are misinformed
      about the possible benefits of research procedures (i.e., therapeutic
      misconception); our participants were aware that the primary purpose of research
      is to gain new knowledge yet they also identified a range of actual health
      benefits arising from their participation.

PMID- 24119204
TI  - Multi-input/output alarming system for patients with inattention caused by higher
      cortical function disorder.
AB  - BACKGROUND: To apply advanced methods of communication, sensing, and
      instrumentation technologies to make a system that can help patients suffering
      from hemispatial neglect caused by higher cortical function disorder. METHOD: By
      using several sensors and actuators, the objective was to construct a tailor-made
      system for each patient. The input part of the system consists of sensors, an
      interface and transmitters. The output part consists of a receiver, logical
      arithmetic, an output interface and actuators. The information from the input
      part is sent to the output part in a wireless manner allowing the mobility of the
      input and output parts. RESULTS: The system and its functionality were realized.
      Voice alarming and neck muscle stimuli were applied to two patients. We could
      verify the applicability of the system to remind the patients to put on their
      wheelchair's brake and raise its footrest before attempting to stand for
      transferring to their beds. CONCLUSION: The designed and constructed multi
      input/output system can be used effectively to alarm the patients.

PMID- 24119205
TI  - Predicting evolutionary responses to climate change in the sea.
AB  - An increasing number of short-term experimental studies show significant effects
      of projected ocean warming and ocean acidification on the performance on marine
      organisms. Yet, it remains unclear if we can reliably predict the impact of
      climate change on marine populations and ecosystems, because we lack sufficient
      understanding of the capacity for marine organisms to adapt to rapid climate
      change. In this review, we emphasise why an evolutionary perspective is crucial
      to understanding climate change impacts in the sea and examine the approaches
      that may be useful for addressing this challenge. We first consider what the
      geological record and present-day analogues of future climate conditions can tell
      us about the potential for adaptation to climate change. We also examine evidence
      that phenotypic plasticity may assist marine species to persist in a rapidly
      changing climate. We then outline the various experimental approaches that can be
      used to estimate evolutionary potential, focusing on molecular tools,
      quantitative genetics, and experimental evolution, and we describe the benefits
      of combining different approaches to gain a deeper understanding of evolutionary
      potential. Our goal is to provide a platform for future research addressing the
      evolutionary potential for marine organisms to cope with climate change. 

PMID- 24119207
TI  - Possibility of decrease in CYP1A2 function in patients with end-stage renal
      disease.
AB  - Propranolol, the substrate of cytochrome P450 (CYP) 1A2 and CYP2D6, has been
      reported to be in high concentrations in end-stage renal disease (ESRD) patients.
      This has been thought to be due to the decrease in the nonrenal clearance of
      propranolol. The objective of this study is to elucidate the reason for the
      decrease in nonrenal clearance in ESRD patients. CYP1A2 and CYP2D6 activities
      were estimated by the phenacetin O-deethylation and methoprolol O-demethylation
      methods, respectively. Pooled normal serum and pooled uremic serum were
      deproteinized by methanol in order to exclude high-molecular-weight compounds. We
      selected as candidate inhibitors: uremic toxins such as 3-indoxyl sulfate, 3
      carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indole-3-acetic acid, and
      hippuric acid, and xanthine derivatives such as allantoin, uric acid, and
      xanthine. In this study, uremic serum was found to inhibit the CYP1A2-mediated
      metabolism of phenacetin to acetaminophen in a concentration-dependent and
      competitive manner. Xanthine also inhibited the metabolism of CYP1A2. On the
      other hand, uremic serum and the four uremic toxins did not inhibit the CYP2D6
      mediated metabolism of metoprolol to O-demethylmetoprolol. In conclusion, this
      study suggests that the increase of the bioavailability of propranolol in ESRD is
      partly induced by the inhibition of the hepatic metabolism of CYP1A2 by xanthine
      in the uremic serum. 

PMID- 24119206
TI  - Activated protein C accelerates venous thrombus resolution through heme oxygenase
      1 induction.
AB  - BACKGROUND: Thrombus resolution is a complex process that involves thrombosis,
      leukocyte-mediated thrombolysis, and the final resolution of inflammation.
      Activated protein C (APC) is an anticoagulant that also possesses
      immunoregulatory activities. AIM: In this study, we sought to examine the effects
      of APC administration on thrombus resolution using a mouse model of deep vein
      thrombosis by ligating the inferior vena cava (IVC). METHODS: The IVCs of C57BL/6
      mice were ligated. Beginning on day 4 post IVC ligation, mice were injected
      intraperitoneally daily with APC, APC plus an heme oxygenase-1 (HO-1) inhibitor
      Sn-protoporphyrin IX (SnPP), SnPP alone, or vehicle control. At different time
      points following surgery, the thrombus-containing IVCs were weighed and then
      analyzed by use of biochemical assays and histology. RESULTS: Venous thrombi
      reached maximum size on day 4 post ligation. The APC-treated group exhibited a
      significant reduction in thrombus weights on day 12 but not on day 7 compared
      with control mice. The enhanced thrombus resolution in APC-treated mice
      correlated with an increased HO-1 expression and a reduced interleukin-6
      production. No significant difference was found in urokinase-type plasminogen
      activator, plasminogen activator inhibitor-1, or matrix metalloproteinase-2 and 
      9 between APC-treated and control mice. Coinjection of the HO-1 inhibitor SnPP
      abolished the ability of APC to enhance thrombus resolution. CONCLUSIONS: Our
      data show that APC enhances the resolution of existing venous thrombi via a
      mechanism that is in part dependent on HO-1, suggesting that APC could be used as
      a potential treatment for patients with deep vein thrombosis to accelerate
      thrombus resolution.

PMID- 24119208
TI  - Share with women. Breastfeeding and working.

PMID- 24119209
TI  - Trophic and proliferative effects of Shh on motor neurons in embryonic spinal
      cord culture from wildtype and G93A SOD1 mice.
AB  - BACKGROUND: The developmental morphogen sonic hedgehog (Shh) may continue to play
      a trophic role in the support of terminally-differentiated motor neurons, of
      potential relevance to motor neuron disease. In addition, it may support the
      proliferation and differentiation of endogenous stem cells along motor neuronal
      lineages. As such, we have examined the trophic and proliferative effects of Shh
      supplementation or Shh antagonism in embryonic spinal cord cell cultures derived
      from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis.
      RESULTS: Shh supported survival, and stimulated growth of motor neurons, neurite
      outgrowth, and neurosphere formation in primary culture derived from both G93A
      SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons,
      especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal
      proliferation compared to controls and especially cyclopamine treated cultures,
      from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and
      differentiation of motor neuron precursors in WT culture. CONCLUSIONS: Shh is
      neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A
      culture in vitro.

PMID- 24119210
TI  - Nutrition and nutraceutical supplements for the treatment of hypertension: part
      III.
AB  - Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction
      play a primary role in the initiation and perpetuation of hypertension,
      cardiovascular disease, and target organ damage. Nutrient-gene interactions and
      epigenetics are predominant factors in promoting beneficial or detrimental
      effects in cardiovascular health and hypertension. Macronutrients and
      micronutrients can prevent, control, and treat hypertension through numerous
      mechanisms related to vascular biology. Oxidative stress, inflammation, and
      autoimmune dysfunction initiate and propagate hypertension and cardiovascular
      disease. There is a role for the selected use of single and component
      nutraceutical supplements, vitamins, antioxidants, and minerals in the treatment
      of hypertension based on scientifically controlled studies that complement
      optimal nutrition, coupled with other lifestyle modifications. 

PMID- 24119211
TI  - Primary prevention of cardiovascular events in patients with major mental
      illness: a possible role for statins.
AB  - OBJECTIVES: To examine the need for and the possible benefits and risks of statin
      therapy in patients with major mental illness. METHODS: Patients with psychiatric
      conditions, especially those with major mental illnesses such as schizophrenia
      and bipolar disorder, are at increased risk of overweight, obesity, dyslipidemia,
      diabetes mellitus, and the metabolic syndrome, all of which increase the risk of
      cardiovascular disease, cerebrovascular disease, and mortality. The literature on
      the subject was qualitatively reviewed. RESULTS: Primary prevention benefits with
      statins are well known in the general population of high-risk patients; recent
      evidence suggests that statins also carry primary prevention benefits in low-risk
      subjects. Regrettably, the primary prevention of cardiovascular and
      cerebrovascular events in psychiatry is a neglected area in clinical practice as
      well as in interventional research, whether in high- or in low-risk patients.
      Initial concerns notwithstanding, psychiatric complications do not appear to be
      important among the adverse effects of statins. Although statins are associated
      with an increased risk of incident diabetes mellitus, myopathy, and other
      untoward consequences, the risk-benefit ratio appears to favor statin use. The
      advisability of using statins in low-risk or medically healthy subjects remains
      debatable. CONCLUSIONS: Overweight, obesity, dyslipidemia, diabetes mellitus, and
      the metabolic syndrome are common in patients with major mental illness, and
      these increase the risk of medical morbidity and mortality. Statin use should
      therefore be considered for the primary prevention of cardiovascular and
      cerebrovascular events in psychiatric patients, especially in those at high risk.

PMID- 24119213
TI  - Self-monitoring of blood glucose in Black Caribbean and South Asian Canadians
      with non-insulin treated Type 2 diabetes mellitus: a qualitative study of
      patients' perspectives.
AB  - BACKGROUND: To examine the views and current practice of SMBG among Black
      Caribbean and South Asian individuals with non-insulin treated Type 2 diabetes
      mellitus. METHODS: Twelve participants completed semi-structured interviews that
      were guided by the Health Belief Model and analyzed using thematic network
      analysis. RESULTS: The frequency of monitoring among participants varied from
      several times a day to once per week. Most participants expressed similar
      experiences regarding their views and practices of SMBG. Minor differences across
      gender and culture were observed. All participants understood the benefits, but
      not all viewed SMBG as beneficial to their personal diabetes management. SMBG can
      facilitate a better understanding and maintenance of self-care behaviours.
      However, it can trigger both positive and negative emotional responses, such as a
      sense of disappointment when high readings are not anticipated, resulting in
      emotional distress. Health care professionals play a key role in the way SMBG is
      perceived and used by patients. CONCLUSION: While the majority of participants
      value SMBG as a self-management tool, barriers exist that impede its practice,
      particularly its cost. How individuals cope with these barriers is integral to
      understanding why some patients adopt SMBG more than others.

PMID- 24119214
TI  - Preserved flow-mediated dilation but delayed time-to-peak diameter in individuals
      with metabolic syndrome.
AB  - INTRODUCTION: Inconsistent evidences of the metabolic syndrome (MetS) impact on
      vascular reactivity raise questions on flow-mediated dilation (FMD)
      discriminatory power for disturbances induced by this clustering of risk factors.
      Previous reports, however, suggest that covariates such as the follow-up of the
      artery diameter changes, the arterial size and shear stress affect FMD responses
      and consequently its discriminatory power for distinctive clinical profiles.
      OBJECTIVE: To determine the impact of MetS on traditional, arterial size- and
      shear-rate-adjusted FMD, the follow-up-derived time-to-peak diameter (TP), as
      well as their power for discriminating subjects with this clustering of risk
      factors from a sample of healthy individuals. METHODS: Twenty-one MetS and ten
      healthy subjects underwent an assessment of endothelial function via FMD.
      RESULTS: Traditional and allometrically scaled FMD did not differ between groups
      (P>0.05) as well as the approach in which the covariate was the peak diameter
      shear rate. In the existence of MetS, TP was longer (67.7 +/- 16.4 s versus
      healthy 42.1 +/- 16.3 s, P = 0.001). ROC curve analysis indicated that TP (AUC =
      0.871 [95% CI, 0.718-1.000]) had greater power of discrimination for MetS than
      FMD approaches. In addition, TP presented a moderate and significant association
      with sE-selectin (r = 0.458, P = 0.048). CONCLUSION: Time-to-peak diameter (TP)
      rather than FMD distinguished MetS from a healthy profile. Therefore, at least in
      subjects with MetS, TP may provide insights into the impact of this clustering of
      risk factors on the vascular phenotype.

PMID- 24119212
TI  - Two interbreeding populations of Saccharomyces cerevisiae strains coexist in
      cachaca fermentations from Brazil.
AB  - In this study, the phylogenetic relationships between cachaca strains of
      Saccharomyces cerevisiae isolated from different geographical areas in Brazil
      were obtained on the basis of sequences of one mitochondrial (COX2) and three
      nuclear (EGT2, CAT8, and BRE5) genes. This analysis allowed us to demonstrate
      that different types of strains coexist in cachaca fermentations: wine strains,
      exhibiting alleles related or identical to those present in European wine
      strains; native strains, containing alleles similar to those found in strains
      isolated from traditional fermentations from Latin America, North America,
      Malaysian, Japan, or West Africa; and their intraspecific hybrids or 'mestizo'
      strains, heterozygous for both types of alleles. Wine strains and hybrids with
      high proportions of wine-type alleles predominate in southern and southeastern
      Brazil, where cachaca production coexists with winemaking. The high frequency of
      'wine-type' alleles in these regions is probably due to the arrival of wine
      immigrant strains introduced from Europe in the nearby wineries due to the
      winemaking practices. However, in north and northeastern states, regions less
      suited or not suited for vine growing and winemaking, wine-type alleles are much
      less frequent because 'mestizo' strains with intermediate or higher proportions
      of 'native-type' alleles are predominant. 

PMID- 24119216
TI  - Attainment of metabolic goals in the integrated UK islet transplant program with
      locally isolated and transported preparations.
AB  - The objective was to determine whether metabolic goals have been achieved with
      locally isolated and transported preparations over the first 3 years of the UK's
      nationally funded integrated islet transplant program. Twenty islet recipients
      with C-peptide negative type 1 diabetes and recurrent severe hypoglycemia
      consented to the study, including standardized meal tolerance tests. Participants
      received a total of 35 infusions (seven recipients: single graft; 11 recipients:
      two grafts: two recipients: three grafts). Graft function was maintained in 80%
      at [median (interquartile range)] 24 (13.5-36) months postfirst transplant.
      Severe hypoglycemia was reduced from 20 (7-50) episodes/patient-year
      pretransplant to 0.3 (0-1.6) episodes/patient-year posttransplant (p < 0.001).
      Resolution of impaired hypoglycemia awareness was confirmed [pretransplant: Gold
      score 6 (5-7); 24 (13.5-36) months: 3 (1.5-4.5); p < 0.03]. Target HbA1c of <7.0%
      was attained/maintained in 70% of recipients [pretransplant: 8.0 (7.0-9.6)%; 24
      (13.5-36) months: 6.2 (5.7-8.4)%; p < 0.001], with 60% reduction in insulin dose
      [pretransplant: 0.51 (0.41-0.62) units/kg; 24 (13.5-36) months: 0.20 (0-0.37)
      units/kg; p < 0.001]. Metabolic outcomes were comparable 12 months posttransplant
      in those receiving transported versus only locally isolated islets [12 month
      stimulated C-peptide: transported 788 (114-1764) pmol/L (n = 9); locally isolated
      407 (126-830) pmol/L (n = 11); p = 0.32]. Metabolic goals have been attained
      within the equitably available, fully integrated UK islet transplant program with
      both transported and locally isolated preparations.

PMID- 24119215
TI  - Species discrimination in Sisyrinchium (Iridaceae): assessment of DNA barcodes in
      a taxonomically challenging genus.
AB  - DNA barcoding aims to develop an efficient tool for species identification based
      on short and standardized DNA sequences. In this study, the DNA barcode paradigm
      was tested among the genera of the tribe Sisyrinchieae (Iridoideae).
      Sisyrinchium, with more than 77% of the species richness in the tribe, is a
      taxonomically complex genus. A total of 185 samples belonging to 98 species of
      Sisyrinchium, Olsynium, Orthrosanthus and Solenomelus were tested using matK,
      trnH-psbA and internal transcribed spacer (ITS). Candidate DNA barcodes were
      analysed either as single markers or in combination. Detection of a barcoding
      gap, similarity-based methods and tree-based analyses were used to assess the
      discrimination efficiency of DNA barcodes. The levels of species identification
      obtained from plastid barcodes were low and ranged from 17.35% to 20.41% for matK
      and 5.11% to 7.14% for trnH-psbA. The ITS provided better results with 30.61
      38.78% of species identified. The analyses of the combined data sets did not
      result in a significant improvement in the discrimination rate. Among the tree
      based methods, the best taxonomic resolution was obtained with Bayesian
      inference, particularly when the three data sets were combined. The study
      illustrates the difficulties for DNA barcoding to identify species in
      evolutionary complex lineages. Plastid markers are not recommended for barcoding
      Sisyrinchium due to the low discrimination power observed. ITS gave better
      results and may be used as a starting point for species identification. 

PMID- 24119217
TI  - 1-Thia-4,7-diaza-spiro[4.4]nonane-3,6-dione: a structural motif for 5
      hydroxytryptamine 6 receptor antagonism.
AB  - A series of potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists based on 1
      thia-4,7-diaza-spiro[4.4]nonane-3,6-dione motif has been disclosed. Enantiomers
      of potent racemate compound 8a (K(i) = 26 nM) displayed difference in activity
      (K(i) of 15 nM versus 855 nM) signaling the influence of the stereochemistry of
      the chiral center on potency. In addition, the potent enantiomer displayed
      significant selectivity in biological activities over several related family
      members.

PMID- 24119218
TI  - Estimating the contribution of the gut to plasma viral load in early SIV
      infection.
AB  - BACKGROUND: There is significant debate about whether the gut plays a major role
      in viral replication and pathology in HIV infection. Here we aimed to estimate
      the contribution of the gut to the total virus observed in plasma, by comparing
      the frequency of different viral mutants in plasma and gut in SIV infection.
      RESULTS: We found that the maximum contribution of gut to plasma viral load
      estimated from rectal biopsy at day 28 post-infection had a median of 10%. The
      estimated values for individual animals ranged from nearly 100% to <3% in 4/14
      animals. Importantly, these are maximum estimates, so that a value of 90%, for
      example, means that the real contribution may be anything between 0 and 90%, just
      not higher than 90%.We also studied the contribution of gut at the peak of plasma
      viral load (day 14). However, since there was very little escape in most animals
      at this time point, we could only estimate the maximal contribution of gut in 4
      animals, in two of which it was <15%. CONCLUSIONS: The role of the gut in HIV is
      a controversial area, with many suggesting that it plays a dominant role in
      driving early infection. Our analysis suggests that, at least by day 28 post
      infection, the gut is not contributing greatly to the plasma viral load.

PMID- 24119219
TI  - Urothelial carcinoma involving the prostate: the association of revised tumour
      stage and coexistent bladder cancer with survival after radical cystectomy.
AB  - OBJECTIVE: To evaluate survival among patients with urothelial carcinoma (UC)
      within the prostate in order to assess the impact of depth of tumour invasion as
      well as the importance of a concurrent bladder tumour. PATIENTS AND METHODS: We
      identified 201 patients who underwent radical cystectomy (RC) between 1980 and
      2006 and were found to have UC involving the prostate. All specimens were re
      reviewed by a genitourinary pathologist. Survival was estimated using the Kaplan
      Meier method and compared with the log-rank test. Cox hazard regression models
      tested the association of clinicopathological variables with outcome. RESULTS: In
      all, 93 patients had pTis disease in the prostate, 43 had pT2 tumours, and 66
      patients were pT4a. The median follow-up was 10.5 years. The 5-year cancer
      specific survival for patients with pTis, pT2, and pT4a prostate UC was 73%, 57%,
      and 21% respectively (P < 0.001). On multivariable analysis, higher prostate
      tumour stage (hazard ratio [HR] 2.09; P = 0.01), positive lymph node status (HR
      2.09; P = 0.002), and concurrent >=pT3 bladder cancer (HR 4.16; P < 0.001) were
      significantly associated with an increased risk of death from UC. CONCLUSIONS:
      Among patients with prostatic UC involvement, depth of tumour invasion was
      significantly associated with cancer-specific mortality, validating the staging
      reclassification. Concurrent locally advanced bladder cancer also negatively
      impacted survival, suggesting the potential prognostic value of reporting a
      secondary tumour stage in such cases.

PMID- 24119220
TI  - Safety and feasibility of levosimendan administration in takotsubo
      cardiomyopathy: a case series.
AB  - BACKGROUND: Levosimendan is a noncatecholamine inotrope that does not increase
      oxygen consumption, utilized for the treatment for acute heart failure with left
      ventricular (LV) systolic dysfunction. Its use in takotsubo cardiomyopathy (TTC),
      a disease that contraindicates the use of catecholamine inotropes, is not well
      known. METHODS: We prospectively analyzed 13 consecutive patients with TTC, low
      ejection fraction (EF) (<35%), and additional Mayo Clinic risk factors who were
      treated with i.v. infusion of levosimendan. Clinical course of patients,
      electrocardiogram presentation, LV function, and adverse events at follow-up were
      recorded. RESULTS: All patients showed an impaired LV function (LVEF at admission
      28 +/- 5%), which significantly improved at discharge (51 +/- 8%, P < 0.001).
      Mean hospital stay was 10 +/- 4 days. Troponin levels at admission were directly
      related to length of hospitalization (r = 0.6, P < 0.001). Male gender (relative
      risk (RR) 1.85, P < 0.05), physical stress (RR 1.90, P < 0.05), ST elevation at
      ECG (RR 1.87, P < 0.05), and absence of chest pain (RR 2.23, P < 0.01) were found
      to be the predictors of longer hospital stay. Only 15% of subjects had adverse
      events during hospital stay; two patients incurred noncardiovascular death at
      follow-up. Age was the only predictor of adverse event at follow-up (RR 2.13, P <
      0.05). CONCLUSIONS: The use of levosimendan may be safe and feasible in patients
      with TTC. Randomized studies are warranted to further confirm these preliminary
      results.

PMID- 24119221
TI  - Comparison of anterior segment morphology following prophylactic laser peripheral
      iridotomy in Caucasian and Chinese eyes.
AB  - BACKGROUND: To compare anterior segment biometric parameters between Caucasians
      and Chinese before and after laser peripheral iridotomy. DESIGN: Prospective
      clinical cohort study. PARTICIPANTS: Caucasian and Chinese primary angle-closure
      suspects. METHODS: Anterior segment optical coherence tomography images captured
      before and after laser peripheral iridotomy were analysed to measure anterior
      segment biometric parameters. Paired Student's t-tests were used for within
      ethnic group comparisons. Univariate and linear mixed-effect regression models
      were used for between-ethnic group comparisons. MAIN OUTCOME MEASURES: Angle
      opening distance, angle recess area, iris thickness, iris curvature, anterior
      chamber area, anterior chamber volume and anterior chamber width. RESULTS:
      Caucasians had significantly greater preoperative angle recess area, anterior
      chamber width, and iris curvature and lower preoperative iris thickness compared
      to Chinese (P < 0.05). Significant postoperative increases in angle opening
      distance, angle recess area, anterior chamber area, anterior chamber volume, and
      anterior chamber width along with significant postoperative decrease in iris
      curvature were observed within both ethnic groups (P < 0.05). However, the amount
      of laser peripheral iridotomy-induced changes in angle opening distance, angle
      recess area, anterior chamber area, anterior chamber volume, anterior chamber
      width, and iris curvature did not differ between the two ethnic groups (P <
      0.05). CONCLUSION: Both Caucasian and Chinese demonstrated opening of anterior
      chamber angle width, expansion of anterior chamber dimensions, and flattening of
      iris convexity after laser peripheral iridotomy. Although certain aspects of
      anterior segment anatomy differed between Caucasians and Chinese preoperatively,
      they did not translate into significant ethnic differences in the amount of laser
      peripheral iridotomy-induced changes in the anterior segment biometric
      parameters.

PMID- 24119222
TI  - Bottlenecks in erucic acid accumulation in genetically engineered ultrahigh
      erucic acid Crambe abyssinica.
AB  - Erucic acid is a valuable industrial fatty acid with many applications. The main
      producers of this acid are today high erucic rapeseed (Brassica napus) and
      mustard (Brassica juncea), which have 45%-50% of erucic acid in their seed oils.
      Crambe abyssinica is an alternative promising producer of this acid as it has 55%
      60% of erucic acid in its oil. Through genetic modification (GM) of three genes,
      we have previously increased the level of erucic acid to 71% (68 mol%) in Crambe
      seed oil. In this study, we further investigated different aspects of oil
      biosynthesis in the developing GM Crambe seeds in comparison with wild-type (Wt)
      Crambe, rapeseed and safflower (Carthamus tinctorius). We show that Crambe seeds
      have very low phosphatidylcholine-diacylglycerol interconversion, suggesting it
      to be the main reason why erucic acid is limited in the membrane lipids during
      oil biosynthesis. We further show that GM Crambe seeds have slower seed
      development than Wt, accompanied by slower oil accumulation during the first 20
      days after flowering (DAF). Despite low accumulation of erucic acid during early
      stages of GM seed development, nearly 86 mol% of all fatty acids accumulated
      between 27 and 50 DAF was erucic acid, when 40% of the total oil is laid down.
      Likely bottlenecks in the accumulation of erucic acid during early stages of GM
      Crambe seed development are discussed.

PMID- 24119223
TI  - Role of testosterone in the pathogenesis, progression, prognosis and comorbidity
      of men with chronic kidney disease.
AB  - Testosterone deficiency and hypogonadism are common conditions in men with
      chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due
      to CKD is thought to contribute to androgen deficiency. Data from experimental
      studies support the hypothesis that exogenous administration of testosterone may
      induce the activation of the renin-angiotensin system (RAS), the production of
      endothelin and the regulation of anti- or/and proinflammatory cytokines involved
      in the pathogenesis of hypertension and kidney damage. On the other hand, low
      testosterone levels in male patients with CKD are paradoxically associated with a
      higher risk of morbidity and mortality, possibly explained by anemia,
      osteoporosis and cardiovascular disease. In this article, we present an overview
      of clinical and experimental studies of the impact of testosterone on the
      progression and prognosis of male patients with CKD; even today, this remains a
      controversial issue. 

PMID- 24119224
TI  - Endogenous preoptic hydrogen sulphide attenuates hypoxia-induced
      hyperventilation.
AB  - AIM: We hypothesized that hydrogen sulphide (H2 S), acting specifically in the
      anteroventral preoptic region (AVPO - an important integrating site of thermal
      and cardiorespiratory responses to hypoxia in which H2 S synthesis has been shown
      to be increased under hypoxic conditions), modulates the hypoxic ventilatory
      response. METHODS: To test this hypothesis, we measured pulmonary ventilation
      (VE) and deep body temperature of rats before and after intracerebroventricular
      (icv) or intra-AVPO microinjection of aminooxyacetate (AOA; CBS inhibitor) or Na2
      S (H2 S donor) followed by 60 min of hypoxia exposure (7% O2 ). Furthermore, we
      assessed the AVPO levels of H2 S of rats exposed to hypoxia. Control rats were
      kept under normoxia. RESULTS: Microinjection of vehicle, AOA or Na2 S did not
      change VE under normoxic conditions. Hypoxia caused an increase in ventilation,
      which was potentiated by microinjection of AOA because of a further augmented
      tidal volume. Conversely, treatment with Na2 S significantly attenuated this
      response. The in vivo H2 S data indicated that during hypoxia the lower the deep
      body temperature the smaller the degree of hyperventilation. Under hypoxia, H2 S
      production was found to be increased in the AVPO, indicating that its production
      is responsive to hypoxia. The CBS inhibitor attenuated the hypoxia-induced
      increase in the H2 S synthesis, suggesting an endogenous synthesis of the gas.
      CONCLUSION: These data provide solid evidence that AVPO H2 S production is
      stimulated by hypoxia, and this gaseous messenger exerts an inhibitory modulation
      of the hypoxic ventilatory response. It is probable that the H2 S modulation of
      hypoxia-induced hyperventilation is at least in part in proportion to metabolism.

PMID- 24119226
TI  - Reply to: is platelet transfusion necessary in cirrhotic patients with
      splenomegaly?

PMID- 24119225
TI  - Perceptual organization of auditory streaming-task relies on neural entrainment
      of the stimulus-presentation rate: MEG evidence.
AB  - BACKGROUND: Humans are able to extract regularities from complex auditory scenes
      in order to form perceptually meaningful elements. It has been shown previously
      that this process depends critically on both the temporal integration of the
      sensory input over time and the degree of frequency separation between concurrent
      sound sources. Our goal was to examine the relationship between these two aspects
      by means of magnetoencephalography (MEG). To achieve this aim, we combined time
      frequency analysis on a sensor space level with source analysis. Our paradigm
      consisted of asymmetric ABA-tone triplets wherein the B-tones were presented
      temporally closer to the first A-tones, providing different tempi within the same
      sequence. Participants attended to the slowest B-rhythm whilst the frequency
      separation between tones was manipulated (0-, 2-, 4- and 10-semitones). RESULTS:
      The results revealed that the asymmetric ABA-triplets spontaneously elicited
      periodic-sustained responses corresponding to the temporal distribution of the A
      B and B-A tone intervals in all conditions. Moreover, when attending to the B
      tones, the neural representations of the A- and B-streams were both detectable in
      the scenarios which allow perceptual streaming (2-, 4- and 10-semitones).
      Alongside this, the steady-state responses tuned to the presentation of the B
      tones enhanced significantly with increase of the frequency separation between
      tones. However, the strength of the B-tones related steady-state responses
      dominated the strength of the A-tones responses in the 10-semitones condition.
      Conversely, the representation of the A-tones dominated the B-tones in the cases
      of 2- and 4-semitones conditions, in which a greater effort was required for
      completing the task. Additionally, the P1 evoked fields' component following the
      B-tones increased in magnitude with the increase of inter-tonal frequency
      difference. CONCLUSIONS: The enhancement of the evoked fields in the source
      space, along with the B-tones related activity of the time-frequency results,
      likely reflect the selective enhancement of the attended B-stream. The results
      also suggested a dissimilar efficiency of the temporal integration of separate
      streams depending on the degree of frequency separation between the sounds.
      Overall, the present findings suggest that the neural effects of auditory
      streaming could be directly captured in the time-frequency spectrum at the sensor
      space level.

PMID- 24119227
TI  - Open label randomized controlled trial assessing the efficacy of mycophenolate
      sodium against other conventional immunosuppressive agents in active systemic
      lupus erythematosus patients without renal involvement.
AB  - AIM: Mycophenolate is an immunosuppressive agent which has been used in systemic
      lupus erythematosus (SLE) patients who have failed conventional therapy. However,
      the use of mycophenolate sodium in extra-renal SLE involvement has yet to be
      established. This study aimed to assess the efficacy of mycophenolate sodium in
      extra-renal SLE. METHODS: A total of 14 SLE patients without renal involvement
      were randomized either to receive mycophenolate sodium or other immunosuppressive
      agents. Patients were assessed monthly from baseline until week 16. Assessment
      parameters included SLE Disease Activity Index (SLEDAI) score, other organ
      specific parameters and immunological parameters, including anti-double stranded
      DNA and C3. Steroid-sparing effect of mycophenolate sodium was also evaluated.
      RESULTS: Mycophenolate sodium produced a significant reduction in SLEDAI scores
      (P < 0.05) after 16 weeks of treatment. Mixed responses were detected in terms of
      organ-specific clinical changes. A positive trend was observed in improvement of
      immunological parameters and steroid dose reduction. No major adverse events were
      reported in this study. CONCLUSION: Mycophenolate sodium is a safe alternative
      therapy in SLE patients with extra-renal involvement. The reduction in SLEDAI
      scores and the observation of no major safety concerns suggest that a larger
      prospective study of mycophenolate sodium in non-renal SLE is warranted.

PMID- 24119228
TI  - Specific inhibition of ectodomain shedding of glycoprotein Ibalpha by targeting
      its juxtamembrane shedding cleavage site.
AB  - BACKGROUND: Ectodomain shedding of glycoprotein Ibalpha (GPIbalpha), a
      proteolytic event in which metalloprotease ADAM17 cleaves the Gly464-Val465 bond
      and releases glycocalicin to the plasma, is considered a critical step in
      mediating clearance of stored platelets. Supporting evidence has largely come
      from studies using ADAM17 inhibitors. However, the definitive proof is lacking
      due to the broad substrate specificity of ADAM17. AIM: To achieve substrate
      specific inhibition of GPIbalpha shedding. METHODS: Development of monoclonal
      antibodies that directly bind the sequence around the GPIbalpha shedding cleavage
      site and inhibit GPIbalpha shedding by blocking ADAM17 access to the cleavage
      site. RESULTS: Six anti-GPIbalpha monoclonal antibodies with varying binding
      affinities were obtained. The prototypic clone, designated 5G6, and its monomeric
      Fab fragment bind specifically purified GPIb-IX complex, human platelets, and
      transgenic murine platelets expressing human GPIbalpha. The clone 5G6 showed
      similar inhibitory potency as a widely used shedding inhibitor GM6001 in both
      constitutive and induced GPIbalpha shedding in human platelets. It does not
      recognize mouse GPIbalpha or inhibit shedding of other platelet receptors.
      Finally, 5G6 binding displays no detectable effect on platelet activation and
      aggregation. CONCLUSIONS: The clone 5G6 specifically inhibits GPIbalpha shedding
      with no detectable effect on platelet functions. The method of substrate-specific
      shedding inhibition by macromolecular binding of the shedding cleavage site can
      be applicable to many other transmembrane receptors undergoing ectodomain
      shedding.

PMID- 24119229
TI  - Tyrosine kinases inhibition by Imatinib slows progression in chronic anti-thy1
      glomerulosclerosis of the rat.
AB  - BACKGROUND: Chronic progressive mesangioproliferative nephropathy represents a
      major cause of end-stage renal disease worldwide. Until now, effective approaches
      to stop or even slow its progression are limited. We tested the effects of an
      inhibitor of PDGF receptor, abl and c-kit tyrosine kinases, Imatinib, in a
      chronic progressive model of mesangioproliferative glomerulosclerosis. METHODS:
      Anti-thy1 glomerulosclerosis was induced by injection of anti-thy1 antibody into
      uninephrectomized Wistar rats. One week after disease induction, according to the
      degree of proteinuria, animals were stratified and assigned to chronic
      glomerulosclerosis (cGS) and cGS plus Imatinib (10 mg/kg body weight/day). In
      week 20, renoprotective actions of Imatinib were analyzed by a set of functional,
      histological and molecular biological parameters. RESULTS: Untreated cGS rats
      showed elevation of systolic blood pressure and marked progression in
      proteinuria, renal fibrosis, cell infiltration, cell proliferation and function
      lost. Administration of Imatinib went along significantly with lower systolic
      blood pressure (-10 mmHg) and proteinuria (-33%). Imatinib administration was
      paralled by significant reductions in tubulointerstitial accumulation of matrix
      proteins (-44%), collagen I deposition (-86%), expression of TGF-beta1 (-30%),
      production of fibronectin (-23%), myofibroblast differentiation (-87%),
      macrophage infiltration (-36%) and cell proliferation (-45%), respectively. In
      comparison with untreated cGS animals, Imatinib therapy lowered also blood
      creatinine (-41%) and blood urea concentrations (-36%) and improved creatinine
      clearance (+25%). Glomerular fibrotic changes were lowered moderately by
      Imatinib. CONCLUSIONS: Therapy with Imatinib limits the progressive course of
      chronic anti-thy1 glomerulosclerosis towards tubulointerstitial fibrosis and
      renal insufficiency. This was paralleled by direct and indirect sign of TGF-beta1
      and PDGF inhibition. The findings suggest that the pharmacological principal of
      inhibition of tyrosine kinases with drugs such as Imatinib might serve as
      approach for limiting progression of human mesangioproliferative
      glomerulosclerosis.

PMID- 24119230
TI  - The clinical relevance of outcomes used in late-onset Pompe disease: can we do
      better?
AB  - Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage
      disorder associated with progressive proximal myopathy, causing a gradual loss of
      muscular function and respiratory insufficiency. Studies of patients with late
      onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT)
      and forced vital capacity (FVC) to assess muscular and respiratory function
      during disease progression or treatment. However, the relevance of these markers
      to late-onset Pompe disease and the minimal clinically important difference
      (MCID) for these endpoints in late-onset Pompe disease have not yet been
      established. A literature search was carried out to identify studies reporting
      the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The
      MCIDs determined in studies of chronic respiratory diseases were used to analyze
      the results of clinical studies of enzyme replacement therapy in late-onset Pompe
      disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from
      baseline in the 6MWT were above or within the MCID established in respiratory
      diseases. Clinical improvement was perceived by patients in 6 of the 10 studies.
      In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes
      from baseline in percentage predicted FVC were above or within the MCID
      established in respiratory diseases and the difference was perceived as either an
      improvement or stabilization by patients. However, applying the 6MWT and FVC
      MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease
      has several important limitations. Outcome measures in muscular dystrophies
      include composite measures of muscle function and gait, as well as Rasch-designed
      and validated tools to assess disease-related quality of life and activities of
      daily living. Given that the relevance to patients with late-onset Pompe disease
      of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear,
      these measures should be evaluated specifically in late-onset Pompe disease and
      alternative outcome measures more specific to neuromuscular disease considered. 

PMID- 24119231
TI  - Association between melanopsin gene polymorphism (I394T) and pupillary light
      reflex is dependent on light wavelength.
AB  - BACKGROUND: Our aim was to determine the association between melanopsin gene
      polymorphism and pupillary light reflex under diverse photic conditions,
      including different intensities and wavelengths. METHODS: A total of 195 visually
      corrected subjects volunteered for investigation of the melanopsin gene of single
      nucleotide polymorphism (SNP) of rs1079610 (I394T). The genotype groups were TT
      (n = 126), TC (n = 55), and CC (n = 8), and 75 of the subjects, including
      subjects with TT (n = 34), TC (n = 33), and CC (n = 8) participated in our
      experiment. Three monochromatic lights with peak wavelengths of 465 nm (blue),
      536 nm (green), and 632 nm (red) were prepared, and each light was projected to
      the subjects with five intensities, 12, 13, 14, 14.5 and 15 log photons/(cm2 s),
      for one minute. The pupil size of the left eye was measured under each light
      condition after a 1-minute adaptation. RESULTS: The pupils of the TC + CC
      genotypes (n = 38) were significantly smaller than those of the TT genotype (n =
      31) under a blue (463 nm) light condition with 15 log photons/(cm2 s) (P < 0.05).
      In contrast, there were no significant differences under green (536 nm) and red
      (632 nm) light conditions. Conversely, relative pupil constrictions of the TC +
      CC genotypes were greater than those of the TT genotype under both blue and green
      conditions with high intensities (14.5 and 15 log photons/(cm2 s)). In contrast,
      there were no significant differences between genotype groups in pupil size and
      relative pupilloconstriction under the red light conditions. CONCLUSIONS: Our
      findings suggest that the melanopsin gene polymorphism (I394T) functionally
      interacts with pupillary light reflex, depending on light intensity and,
      particularly, wavelength, and that under a light condition fulfilling both high
      intensity and short wavelength, the pupillary light response of subjects with the
      C allele (TC + CC) is more sensitive to light than that of subjects with the TT
      genotype.

PMID- 24119233
TI  - Disparity in motorcycle helmet use in Thailand.
AB  - The dispersion of motorcycle related injuries and deaths might be a result of
      disparity in motorcycle helmet use. This study uses national roadside survey
      data, injury sentinel surveillance data and other national data sets in 2010 of
      Thailand, a country with high mortality related to motorcycle injuries, to
      explore the disparity in helmet use, explanatory factors of the disparity. It
      also assessed potential agreement and correlation between helmet use rate
      reported by the roadside survey and the injury sentinel surveillance. This report
      revealed helmet use rate of 43.7%(95% CI:43.6,43.9) nationwide with the highest
      rate (81.8%; 95% CI: 44.0,46.4) in Bangkok. Helmet use rate in drivers (53.3%;
      95% CI: 53.2,53.8) was 2.5 times higher than that in passengers (19.3%; 95%
      CI:18.9,19.7). In relative terms (highest-to-lowest ratio,HLR), geographical
      disparity in helmet use was found to be higher in passengers (HLR = 28.5). Law
      enforcement activities as indicated by the conviction rate of motorcyclists were
      significantly associated with the helmet use rate (spline regression coefficient
      = 3.90, 95% CI: 0.48,7.33). Together with the finding of HLR for conviction rate
      of 87.24, it is suggested that more equitable improvement in helmet use could be
      achieved by more equitable distribution of the police force. Finally, we found
      poor correlation (r = 0.01; p value = 0.76) and no agreement (difference =
      34.29%; 95% CI:13.48%, 55.09%) between roadside survey and injury sentinel
      surveillance in estimating helmet use rate. These findings should be considered a
      warning for employing injury surveillance to monitor policy implementation of
      helmet use.

PMID- 24119232
TI  - Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts
      autophagy in human macrophages.
AB  - Selective autophagy functions to specifically degrade cellular cargo tagged by
      ubiquitination, including bacteria. Strains of the Burkholderia cepacia complex
      (Bcc) are opportunistic pathogens that cause life-threatening infections in
      patients with cystic fibrosis (CF) and chronic granulomatous disease (CGD). While
      there is evidence that defective macrophage autophagy in a mouse model of CF can
      influence B. cenocepacia susceptibility, there have been no comprehensive studies
      on how this bacterium is sensed and targeted by the host autophagy response in
      human macrophages. Here, we describe the intracellular life cycle of B.
      cenocepacia J2315 and its interaction with the autophagy pathway in human cells.
      Electron and confocal microscopy analyses demonstrate that the invading bacteria
      interact transiently with the endocytic pathway before escaping to the cytosol.
      This escape triggers theselective autophagy pathway, and the recruitment of
      ubiquitin, the ubiquitin-binding adaptors p62 and NDP52 and the autophagosome
      membrane-associated protein LC3B, to the bacterial vicinity. However, despite
      recruitment of these key autophagy pathway effectors, B. cenocepacia blocks
      autophagosome completion and replicates in the host cytosol. We find that a pre
      infection increase in cellular autophagy flux can significantly inhibit B.
      cenocepacia replication and that lower autophagy flux in macrophages from
      immunocompromised CGD patients could contribute to increased B. cenocepacia
      susceptibility, identifying autophagy manipulation as a potential therapeutic
      approach to reduce bacterial burden in B. cenocepacia infections. 

PMID- 24119234
TI  - Features Amplifying Dermoscopy (FAD) for better evaluation in difficult pigmented
      and non-pigmented melanocytic skin tumors.

PMID- 24119235
TI  - An integrative review of knowing the patient.
AB  - PURPOSE: The purpose of this article is to characterize the concept knowing the
      patient as reflected in the contemporary nursing literature and to consider
      implications for nursing practice. ORGANIZING CONSTRUCT: A literature review was
      conducted to identify primary source publications concerned with knowing the
      patient within the nursing discipline. METHODS: Cumulative Index to Nursing and
      Allied Health, PubMed, and Cochrane Library databases were queried using the
      phrase knowing the patient to identify relevant peer-reviewed literature from
      1996 through 2013. FINDINGS: The review produced 21 publications; knowing the
      patient was the topic of inquiry in only 5 of these. Knowing the patient emerged
      as a finding in 16 investigations and was described as affecting nurses' ability
      to provide safe care, develop positive relationships, and engage in expert
      practice. Patterns identified across studies were illustrated in a model
      representing the process of knowing the patient, including factors of the nurse's
      internal environment, information practices to develop knowledge and create
      meaning, and the nurse's response. The process of knowing the patient occurs
      within the context of relationship with the patient and in an environment that is
      temporal in nature. CONCLUSIONS: While knowing the patient continues to be a
      prominent concept in the nursing literature, practice environments may not
      provide the conditions necessary to support the process, particularly temporal
      factors of time availability, sustained contact, continuity, and consistency.
      CLINICAL RELEVANCE: Findings inform the development of professional practice
      models that support knowing the patient.

PMID- 24119236
TI  - Nutrition and nutraceutical supplements for the treatment of hypertension: part
      II.
AB  - Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction
      play a primary role in the initiation and perpetuation of hypertension,
      cardiovascular disease, and target organ damage. Nutrient-gene interactions and
      epigenetics are predominant factors in promoting beneficial or detrimental
      effects in cardiovascular health and hypertension. Macronutrients and
      micronutrients can prevent, control, and treat hypertension through numerous
      mechanisms related to vascular biology. Oxidative stress, inflammation, and
      autoimmune dysfunction initiate and propagate hypertension and cardiovascular
      disease. There is a role for the select use of single and component nutraceutical
      supplements, vitamins, antioxidants, and minerals in the treatment of
      hypertension based on scientifically controlled studies, which complement optimal
      nutrition, coupled with other lifestyle modifications. 

PMID- 24119238
TI  - An empirical evaluation of the MATRICS Consensus Cognitive Battery in bipolar
      disorder.
AB  - OBJECTIVES: There is a large body of evidence to indicate that neurocognitive
      impairments in bipolar disorder (BD) may represent viable endophenotypes;
      however, a standard consensus-based battery of cognitive tests used to measure
      them is yet to appear. There is potential for a neurocognitive battery which was
      developed for use in the related disorder, schizophrenia - the MATRICS Consensus
      Cognitive Battery (MCCB) - to provide a consistent measurement tool with a
      standard to which the cognitive capacity of BD can be compared to other
      disorders. However, its suitability for capturing neurocognitive impairment in BD
      cohorts is not well established. Moreover, neurocognitive tests recently
      recommended by the International Society for Bipolar Disorders (ISBD) for
      inclusion in a consensus neurocognitive battery for BD have not been evaluated in
      the context of the MCCB. An evaluation of (i) the clinical efficacy of the MCCB
      and (ii) the tests recommended by the ISBD in a BD cohort were the aims of the
      current study. METHODS: A total of 50 patients with BD (mean age = 38 years) and
      52 healthy controls (mean age = 34 years) completed all of the MCCB subtests, in
      addition to the well-recognized Trail Making Test-Part B and the Colour-Word
      Stroop. RESULTS: Multivariate analyses of variance of the MCCB domains revealed a
      significant group effect for overall cognition, and significantly reduced patient
      performance on speed of processing, working memory, and visual and verbal
      learning. A second multivariate analysis of variance using a newly created
      composite score called executive function, comprising scores on an existing MCCB
      subtest in addition to TMT-B and Colour-Word Stroop, revealed significant
      differences on this domain as well. Subgroup analysis indicated that there were
      no differences in any domain score performance between symptomatic and euthymic
      patients, or bipolar I and II disorder patient groups. CONCLUSIONS: Our findings
      suggest that the MCCB and two additionally recommended ISBD executive function
      measures form a promising consensus-based research tool for examining
      neurocognition in BD.

PMID- 24119237
TI  - An overview of patient involvement in healthcare decision-making: a situational
      analysis of the Malaysian context.
AB  - BACKGROUND: Involving patients in decision-making is an important part of patient
      centred care. Research has found a discrepancy between patients' desire to be
      involved and their actual involvement in healthcare decision-making. In Asia,
      there is a dearth of research in decision-making. Using Malaysia as an exemplar,
      this study aims to review the current research evidence, practices, policies, and
      laws with respect to patient engagement in shared decision-making (SDM) in Asia.
      METHODS: In this study, we conducted a comprehensive literature review to collect
      information on healthcare decision-making in Malaysia. We also consulted medical
      education researchers, key opinion leaders, governmental organisations, and
      patient support groups to assess the extent to which patient involvement was
      incorporated into the medical curriculum, healthcare policies, and legislation.
      RESULTS: There are very few studies on patient involvement in decision-making in
      Malaysia. Existing studies showed that doctors were aware of informed consent,
      but few practised SDM. There was limited teaching of SDM in undergraduate and
      postgraduate curricula and a lack of accurate and accessible health information
      for patients. In addition, peer support groups and 'expert patient' programmes
      were also lacking. Professional medical bodies endorsed patient involvement in
      decision-making, but there was no definitive implementation plan. CONCLUSION: In
      summary, there appears to be little training or research on SDM in Malaysia. More
      research needs to be done in this area, including baseline information on the
      preferred and actual decision-making roles. The authors have provided a set of
      recommendations on how SDM can be effectively implemented in Malaysia.

PMID- 24119239
TI  - Effect of transcranial magnetic stimulation on rectal sensitivity in irritable
      bowel syndrome: a randomized, placebo-controlled pilot study.
AB  - AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor
      cortex can induce analgesic effects in patients with chronic pain syndromes
      through its effect on central pain-modulatory systems. Our aim was to evaluate
      the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS)
      patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21
      IBS patients (11 women and 10 men; mean age 44.0 +/- 12.6 years) were randomized,
      using a double-blind crossover protocol, to active or sham rTMS for 5 days of
      treatment. The primary outcome was the increase in the pressure pain threshold
      after rTMS. Secondary outcomes were the changes in maximum tolerated rectal
      volume, rectal compliance and average pain intensity between baseline and the end
      of the treatments. RESULTS: There were no statistically significant differences
      between active and sham rTMS in terms of an increase in the pressure pain
      threshold, maximum tolerated volume and rectal compliance at the end of the
      treatments compared with baseline. However, in the subgroup of patients with the
      most marked rectal hypersensitivity, the volume threshold was significantly
      improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a
      significant improvement in pain regardless of the type of stimulation.
      CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our
      primary end-point. However, the effect of rTMS on rectal tolerated volume in the
      most hypersensitive patients was encouraging enough to plan more powered studies.

PMID- 24119241
TI  - Tumour-associated macrophages are associated with vascular endothelial growth
      factor expression in canine mammary tumours.
AB  - Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis
      including an important role in angiogenesis. In this study, we describe the
      relationship between TAMs and angiogenesis in canine mammary tumours (CMT).
      Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and
      benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387,
      vascular endothelial growth factor VEGF and CD31 expression. A statistical
      analysis was carried out to assess possible associations with clinicopathological
      variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387
      expression, were significantly associated with malignant CMT (P < 0.001) and VEGF
      positive tumours (P = 0.002) and also associated with VEGF expression within
      malignant CMT (P = 0.043). Associations with clinicopathological variables were
      found between TAMs and the presence of infiltrative growth (P = 0.031), low
      tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results
      support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs
      may represent a therapeutic target in this disease. 

PMID- 24119242
TI  - Synthesis and evaluation of novel oleanolic acid derivatives as potential
      antidiabetic agents.
AB  - Antidiabetic agents simultaneously inhibiting hepatic glucose production and
      stimulating hepatic glucose consumption could apply a better control over
      hyperglycemia. A series of oleanolic acid derivatives with bulky substituents at
      C-3 position were designed and synthesized in order to search for this kind of
      agents. All of the compounds were evaluated biologically in vitro using glycogen
      phosphorylase and HepG2 cells. The results indicated that several derivatives
      exhibited moderate-to-good inhibitory activities against glycogen phosphorylase.
      Compound 8g showed the best inhibition with an IC50 value of 5.4 MUm. Moreover,
      most of the derivatives were found to increase the glucose consumption in HepG2
      cells in a dose-dependent manner. The possible binding mode of compound 8g with
      glycogen phosphorylase was also explored by docking study. 8g was found to have
      hydrogen bonding interactions with Arg193, Arg310, and Arg60 of the allosteric
      site. 

PMID- 24119240
TI  - Developmental delays and dental caries in low-income preschoolers in the USA: a
      pilot cross-sectional study and preliminary explanatory model.
AB  - BACKGROUND: Anecdotal evidence suggests that low-income preschoolers with
      developmental delays are at increased risk for dental caries and poor oral
      health, but there are no published studies based on empirical data. The purpose
      of this pilot study was two-fold: to examine the relationship between
      developmental delays and dental caries in low-income preschoolers and to present
      a preliminary explanatory model on the determinants of caries for enrollees in
      Head Start, a U.S. school readiness program for low-income preschool-aged
      children. METHODS: Data were collected on preschoolers ages 3-5 years at two Head
      Start centers in Washington, USA (N = 115). The predictor variable was
      developmental delay status (no/yes). The outcome variable was the prevalence of
      decayed, missing, and filled surfaces (dmfs) on primary teeth. We used multiple
      variable Poisson regression models to test the hypothesis that within a
      population of low-income preschoolers, those with developmental delays would have
      increased dmfs prevalence than those without developmental delays. RESULTS:
      Seventeen percent of preschoolers had a developmental delay and 51.3% of
      preschoolers had >=1 dmfs. Preschoolers with developmental delays had a dmfs
      prevalence ratio that was 1.26 times as high as preschoolers without
      developmental delays (95% CI: 1.01, 1.58; P < .04). Other factors associated with
      increased dmfs prevalence ratios included: not having a dental home (P = .01);
      low caregiver education (P < .001); and living in a non-fluoridated community (P
      < .001). CONCLUSIONS: Our pilot data suggest that developmental delays among low
      income preschoolers are associated with increased primary tooth dmfs. Additional
      research is needed to further examine this relationship. Future interventions and
      policies should focus on caries prevention strategies within settings like Head
      Start classrooms that serve low-income preschool-aged children with additional
      targeted home- and community-based interventions for those with developmental
      delays.

PMID- 24119243
TI  - Characterization of Dicrocoelium dendriticum haplotypes from sheep and cattle in
      Iran based on the internal transcribed spacer 2 (ITS-2) and NADH dehydrogenase
      gene (nad1).
AB  - The present study assessed whether the genetic variation among different hosts
      (sheep and cattle) and geographical isolates (n= 28) of Dicrocoelium dendriticum
      from Iran is present based on mitochondrial (nad1) and ribosomal (ITS-2) DNA
      markers. Molecular analysis revealed the presence of at least ten and two
      distinct haplotypes in the NADH dehydrogenase gene (nad1) and internal
      transcribed spacer 2 (ITS-2), respectively. The nad1 and ITS-2 sequence data were
      deposited in GenBank under accession numbers, JX050110-134 and JQ966972-3.
      According to the results of our study, ND-D and ITS-A are established as being
      the predominant haplotypes of D. dendriticum in Iran. The Iranian isolates showed
      a higher intraspecific genetic diversity of 0-0.97% for nad1, compared to 0-0.42%
      for ITS-2. The alignment and comparison of nad1 and ITS-2 sequences revealed
      eight and one polymorphic sites, respectively. In the nad1 sequences, six were
      silent and two nucleotide substitutions were responsible for amino acid
      alterations. A phylogenetic analysis of the sequence data revealed that host
      associations and geographic location are not likely useful markers for D.
      dendriticum haplotype classification. Consequently, sequencing results obtained
      from the nad1 gene as a mitochondrial marker for the first time in this study
      would provide a valuable tool to analyse further molecular details of D.
      dendriticum worldwide. 

PMID- 24119244
TI  - Ecological niche models in phylogeographic studies: applications, advances and
      precautions.
AB  - The increased availability of spatial data and methodological developments in
      species distribution modelling has lead to concurrent advances in phylogeography,
      broadening the scope of questions studied, as well as providing unprecedented
      insights. Given the species-specific nature of the information provided by
      ecological niche models (ENMs), whether it is on the environmental tolerances of
      species or their estimated distribution, today or in the past, it is perhaps not
      surprising that ENMs have rapidly become a common tool in phylogeographic
      analysis. Such information is essential to phylogeographic tests that provide
      important biological insights. Here, we provide an overview of the different
      applications of ENMs in phylogeographic studies, detailing specific studies and
      highlighting general limitations and challenges with each application. Given that
      the full potential of integrating ENMs into phylogeographic cannot be realized
      unless the ENMs themselves are carefully applied, we provide a summary of best
      practices with using ENMs. Lastly, we describe some recent advances in how
      quantitative information from ENMs can be integrated into genetic analyses,
      illustrating their potential use (and key concerns with such implementations), as
      well as promising areas for future development. 

PMID- 24119245
TI  - A systematic review of reviews of behavioral interventions to promote condom use.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are a major public health
      problem. Realistically, condom use is still the primary means to prevent STIs.
      Because many behavioral intervention studies have been performed to increase
      condom use across multiple populations and many reviews have been done, a review
      of all these reviews is warranted. AIMS: The purpose of this paper is to examine
      Level I evidence of behavioral intervention studies to promote condom use. The
      purpose of this evidence-based practice (EBP) review is to examine the evidence
      and determine: (a) if behavioral interventions are effective; and (b) if they
      are, what are the common characteristics of successful interventions that need to
      be implemented in practice. METHODS: A systematic search for literature was
      conducted in the following databases: Cochrane Library, Cumulative Index of
      Nursing and Allied Health Literature (CINAHL), MEDLINE, PubMed, and Psychological
      and Behavioral Sciences Collection. The following parameters were used for the
      search: (a) a meta-analysis or level 1 synthesis of literature containing only
      intervention (randomized control trials or quasi-experimental) studies; (b) peer
      reviewed journals; (c) published in the past 10 years (2002-2012); (d) had
      adolescents or adults as the sample (13-44 years of age); and (e) were published
      in English. RESULTS: Behavioral interventions were effective in promoting condom
      use and other safer sexual practices and reducing STIs. They were not effective
      in promoting abstinence. Tailoring to certain characteristics of the population
      and including skills building exercises were primary characteristics in the
      successful interventions IMPLICATIONS: There is a preponderance of evidence that
      behavioral interventions do promote condom use and reduce STIs across diverse
      groups of individuals. Clinicians can use these interventions with confidence in
      practice.

PMID- 24119246
TI  - Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive
      rats.
AB  - AIM: Autophagy is a subcellular degradation mechanism important for muscle
      maintenance. Hypertension induces well-characterized pathological changes to the
      heart and is associated with impaired function and increased apoptotic signalling
      in skeletal muscle. We examined whether essential hypertension affects several
      autophagy markers in skeletal and cardiac muscle. METHODS: Immunoblotting and qRT
      PCR were used to measure autophagy-related proteins/mRNA in multiple skeletal
      muscles as well as left ventricle (LV) of spontaneously hypertensive rats (SHR)
      and normotensive Wistar-Kyoto rats (WKY). RESULTS: Skeletal muscles of
      hypertensive rats had decreased (P < 0.01) cross-sectional area of type I fibres
      (e.g. soleus WKY: 2952.9 +/- 64.4 MUm(2) vs. SHR: 2579.9 +/- 85.8 MUm(2)) and a
      fibre redistribution towards a 'fast' phenotype. Immunoblot analysis revealed
      that some SHR skeletal muscles displayed a decreased LC3II/I ratio (P < 0.05),
      but none showed differences in p62 protein. LC3 and LAMP2 mRNA levels were
      increased approx. 2-3-fold in all skeletal muscles (P < 0.05), while cathepsin
      activity, cathepsin L mRNA and Atg7 protein were increased 16-17% (P < 0.01), 2-3
      fold (P < 0.05) and 29-49% (P < 0.01), respectively, in fast muscles of
      hypertensive animals. Finally, protein levels of BAG3, a marker of chaperone
      assisted selective autophagy, were 18-25% lower (P < 0.05) in SHR skeletal
      muscles. In the LV of SHR, LC3I and p62 protein were elevated 34% (P < 0.05) and
      47% (P < 0.01), respectively. Furthermore, p62 mRNA was 68% higher (P < 0.05),
      while LAMP2 mRNA was 45% lower (P < 0.05), in SHR cardiac muscle. There was no
      difference in Beclin1, Atg7, Bnip3 or BAG3 protein in the LV between strains.
      CONCLUSION: These results suggest that autophagy is altered in skeletal and
      cardiac muscle during hypertension.

PMID- 24119247
TI  - Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico:
      study protocol.
AB  - BACKGROUND: Trypanosoma cruzi has been divided into Discrete Typing Units I and
      non-I (II-VI). T. cruzi I is predominant in Mexico and Central America, while non
      I is predominant in most of South America, including Argentina. Little is known
      about congenital transmission of T. cruzi I. The specific aim of this study is to
      determine the rate of congenital transmission of T. cruzi I compared to non-I.
      METHODS/DESIGN: We are conducting a prospective study to enroll at delivery,
      10,000 women in Argentina, 7,500 women in Honduras, and 13,000 women in Mexico.
      We are measuring transmitted maternal T. cruzi antibodies by performing two rapid
      tests in cord blood (Stat-Pak, Chembio, Medford, New York, and Trypanosoma
      Detect, InBios, Seattle, Washington). If at least one of the results is positive,
      we are identifying infants who are congenitally infected by performing
      parasitological examinations on cord blood and at 4-8 weeks, and serological
      follow-up at 10 months. Serological confirmation by ELISA (Wiener, Rosario,
      Argentina) is performed in cord and maternal blood, and at 10 months. We also are
      performing T. cruzi standard PCR, real-time quantitative PCR and genotyping on
      maternal venous blood and on cord blood, and serological examinations on
      siblings. Data are managed by a Data Center in Montevideo, Uruguay. Data are
      entered online at the sites in an OpenClinica data management system, and digital
      pictures of data forms are sent to the Data Center for quality control. Weekly
      reports allow for rapid feedback to the sites.

PMID- 24119248
TI  - Results of implementation of preventive recommendations for tuberculosis after
      renal transplantation in an endemic area.
AB  - This retrospective cohort study assessed the results of the implementation of
      preventive recommendations for tuberculosis (TB) among renal transplant
      recipients in an endemic area (Rio de Janeiro, Brazil). Subjects were defined as
      at high risk for TB if they had latent tuberculosis infection (LTBI), reported
      recent close contact with individuals with TB or received a graft from a donor
      with LTBI. A 6-month course of isoniazid preventive therapy (IPT) was targeted to
      high-risk subjects. The study end point was TB confirmed by culture. Altogether,
      535 patients were included. Median follow-up was 59 months. The overall
      cumulative incidence of TB was 2.1% while among the 274 patients in whom the
      preventive protocol was fully implemented, the incidence was only 0.7%. The
      incidence of TB among 75 high-risk recipients not treated with isoniazid (7%) was
      significantly higher than that observed in 209 untreated low-risk patients (1%, p
      = 0.006) and in 65 high-risk subjects that received IPT (no case, p = 0.03). In
      conclusion, the implementation of preventive recommendations for TB in an endemic
      area allowed the appropriate discrimination between high- and low-risk renal
      transplant recipients and was associated with long-term reduction in the
      incidence of this complication among high-risk subjects.

PMID- 24119249
TI  - Release of contaminants from a heterogeneously fractured low permeability unit
      underlying a DNAPL source zone.
AB  - The invasion of DNAPL into fractured low permeability deposits results in the
      formation of secondary source zones that represent a long-term source of VOCs to
      adjacent aquifers. We present data from a site underlain by a fractured mudstone
      contaminated with TCE DNAPL that was poised for release following remediation of
      the overlying aquifer. Observations of contaminant distributions and fracture
      networks from the site and a nearby mudstone exposure respectively, enabled
      prediction of the imminent aquifer recontamination. The fractures, likely formed
      by gypsum dissolution, were characterised by fracture apertures and spacings that
      ranged from 0.01 to 49 mm and 0.047 to 3.37 m (10th and 90th percentile values)
      respectively. Numerical model results show that prediction of outward mass flux
      in the first year was highly variable (8 to 32 g/m2/d for an initial constant
      concentration with depth profile) and dependent on both the fracture spacing and
      aperture and the contaminant distribution. However after 1 year, assuming a
      heterogeneous distribution of fractures, mass flux was predictable within a
      narrow range of values (at 20 years; 0.04-0.08 g/m2/d). Similar results were
      obtained from more typical fracture networks with spacings of 0.1 to 0.5 m and
      apertures of 10 to 100 MUm. These results suggest that when considering potential
      recontamination in a bounding aquifer, fracture characterisation may not be
      necessary and instead the focus should be on determining the surface area
      contributing contaminant mass to an aquifer, the contaminant concentration depth
      profiles, the hydraulic properties of the receiving aquifer and the elapsed time
      since aquifer remediation.

PMID- 24119250
TI  - The anti-ribosomal P antibodies and prognosis in autoimmune hepatitis.

PMID- 24119251
TI  - Plasticity of primary microglia on micropatterned geometries and spontaneous long
      distance migration in microfluidic channels.
AB  - BACKGROUND: Microglia possess an elevated grade of plasticity, undergoing several
      structural changes based on their location and state of activation. The first
      step towards the comprehension of microglia's biology and functional responses to
      an extremely mutable extracellular milieu, consists in discriminating the
      morphological features acquired by cells maintained in vitro under diverse
      environmental conditions. Previous work described neither primary microglia grown
      on artificially patterned environments which impose physical cues and
      constraints, nor long distance migration of microglia in vitro. To this aim, the
      present work exploits artificial bio-mimetic microstructured substrates with
      pillar-shaped or line-grating geometries fabricated on poly(dimethylsiloxane) by
      soft lithography, in addition to microfluidic devices, and highlights some
      morphological/functional characteristics of microglia which were underestimated
      or unknown so far. RESULTS: We report that primary microglia selectively adapt to
      diverse microstructured substrates modifying accordingly their morphological
      features and behavior. On micropatterned pillar-shaped geometries, microglia
      appear multipolar, extend several protrusions in all directions and form distinct
      pseudopodia. On both micropatterned line-grating geometries and microfluidic
      channels, microglia extend the cytoplasm from a roundish to a stretched,
      flattened morphology and assume a filopodia-bearing bipolar structure. Finally,
      we show that in the absence of any applied chemical gradient, primary microglia
      spontaneously moves through microfluidic channels for a distance of up to 500 MUm
      in approximately 12 hours, with an average speed of 0.66 MUm/min. CONCLUSIONS: We
      demonstrate an elevated grade of microglia plasticity in response to a mutable
      extracellular environment, thus making these cells an appealing population to be
      further exploited for lab on chip technologies. The development of microglia
      based microstructured substrates opens the road to novel hybrid platforms for
      testing drugs for neuroinflammatory diseases.

PMID- 24119252
TI  - Practical considerations in the use of novel oral anticoagulants for stroke
      prevention in nonvalvular atrial fibrillation.
AB  - Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with
      an increased risk of stroke. The role of anticoagulation therapy in the
      prevention of thrombosis and stroke is of critical importance for patients with
      AF. Limitations with vitamin K antagonists (VKAs), the current standard of care,
      have led to the development of novel oral anticoagulants (NOACs) that target
      either thrombin (dabigatran etexilate) or activated factor X (rivaroxaban,
      apixaban, and edoxaban). In comparison with traditional VKAs such as warfarin,
      these NOACs offer several pharmacologic advantages, including rapid onset of
      action, no significant food interactions, low potential for drug-drug
      interactions, and no requirement for routine coagulation monitoring. Completed
      phase-III clinical trials have demonstrated the therapeutic potential of
      dabigatran, rivaroxaban, and apixaban in comparison with warfarin for stroke
      prevention in patients with nonvalvular AF (NVAF). While the future utility of
      NOACs in preventing stroke in patients with NVAF looks promising, several
      practical issues, including the current lack of a reversal strategy and use of
      these agents in older patients with renal dysfunction, must be considered.
      Clinician and patient understanding of such issues will be important for the safe
      and effective use of NOACs. 

PMID- 24119253
TI  - Basic nursing care to prevent nonventilator hospital-acquired pneumonia.
AB  - PURPOSE: Nonventilator hospital-acquired pneumonia (NV-HAP) is an underreported
      and unstudied disease, with potential for measurable outcomes, fiscal savings,
      and improvement in quality of life. The purpose of our study was to (a) identify
      the incidence of NV-HAP in a convenience sample of U.S. hospitals and (b)
      determine the effectiveness of reliably delivered basic oral nursing care in
      reducing NV-HAP. DESIGN: A descriptive, quasi-experimental study using
      retrospective comparative outcomes to determine (a) the incidence of NV-HAP and
      (b) the effectiveness of enhanced basic oral nursing care versus usual care to
      prevent NV-HAP after introduction of a basic oral nursing care initiative.
      METHODS: We used the International Statistical Classification of Diseases and
      Related Problems (ICD-9) codes for pneumonia not present on admission and
      verified NV-HAP diagnosis using the U.S. Centers for Disease Control and
      Prevention diagnostic criteria. We completed an evidence-based gap analysis and
      designed a site-specific oral care initiative designed to reduce NV-HAP. The
      intervention process was guided by the Influencer Model (see Figure) and
      participatory action research. FINDINGS: We found a substantial amount of
      unreported NV-HAP. After we initiated our oral care protocols, the rate of NV-HAP
      per 100 patient days decreased from 0.49 to 0.3 (38.8%). The overall number of
      cases of NV-HAP was reduced by 37% during the 12-month intervention period. The
      avoidance of NV-HAP cases resulted in an estimated 8 lives saved, $1.72 million
      cost avoided, and 500 extra hospital days averted. The extra cost for therapeutic
      oral care equipment was $117,600 during the 12-month intervention period. Cost
      savings resulting from avoided NV-HAP was $1.72 million. Return on investment for
      the organization was $1.6 million in avoided costs. CONCLUSIONS: NV-HAP should be
      elevated to the same level of concern, attention, and effort as prevention of
      ventilator-associated pneumonia in hospitals. CLINICAL RELEVANCE: Nursing needs
      to lead the way in the design and implementation of policies that allow for
      adequate time, proper oral care supplies, ease of access to supplies, clear
      procedures, and outcome monitoring ensuring that patients are protected from NV
      HAP.

PMID- 24119254
TI  - Evaluation of mental stress by physiological indices derived from finger
      plethysmography.
AB  - BACKGROUND: Quantitative evaluation of mental stress is important to prevent
      stress-related disorders. Finger plethysmography (FPG) is a simple noninvasive
      method to monitor peripheral circulation, and provides many physiological
      indices. Our purpose is to investigate how FPG-derived indices reflect on mental
      stress, and to clarify any association between these physiological indices and
      subjective indices of mental stress. METHODS: Thirty-one healthy women (mean age,
      22 years +/- 2) participated. The participants rested by sitting on a chair for
      10 min. They then performed a computerized version of the Stroop color-word
      conflict test (CWT) for 10 min. Finally, they rested for 10 min. FPG was recorded
      throughout the experiment. The participants completed a brief form of the Profile
      of Mood States (POMS) questionnaire before and after the test. Using the FPG
      data, we conducted chaos analysis and fast Fourier transform analysis, and
      calculated chaotic attractors, the largest Lyapunov exponent, a high-frequency
      (HF) component, a low-to-high-frequency (LF/HF) ratio, finger pulse rate and
      finger pulse wave amplitude. RESULTS: The HF component decreased and the LF/HF
      ratio increased significantly during the test (P < 0.01), while the confusion
      subscale of POMS increased after the test (P < 0.05). During testing, finger
      pulse rate significantly increased (P < 0.001), and the finger pulse wave
      amplitude decreased (P < 0.001). The attractor size reduced during testing and
      returned to a baseline level afterwards. Although the largest Lyapunov exponent
      showed no significant change during testing, significant negative correlation
      with the tension-anxiety subscale of POMS was observed at the beginning (P <
      0.01). A significant negative correlation between the LF/HF ratio and two
      subscales was also observed in the beginning and middle of the test (P < 0.05).
      There were no correlations during the rest periods. CONCLUSIONS: The
      physiological indices derived from FPG were changed by mental stress. Our
      findings indicate that FPG is one of the easiest methods to evaluate mental
      stress quantitatively. In particular, the largest Lyapunov exponent and the LF/HF
      ratio might be associated with acute mental stress. Farther examination is needed
      to find any association between the physiological indices and various types of
      mental stress.

PMID- 24119255
TI  - Nonsyndromic types of ichthyoses - an update.
AB  - Ichthyoses are genetically determined Mendelian disorders of cornification
      (MEDOC) that are characterized by universal scaling. Today we distinguish between
      non-syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type
      (prevalence 1:100) and is caused by autosomal semi-dominant filaggrin mutations.
      It is associated with a higher risk for the development of atopic diseases, such
      as atopic eczema and allergic rhinitis. Recessive X-linked ichthyosis (RXLI)
      occurs almost exclusively in boys; in Germany it has a prevalence of around
      1:4,000. It is caused by steroid sulfatase deficiency and is often associated
      with further clinical problems, such as cryptorchidism (~20%) or social
      communication deficits, such as attention deficit hyperactivity syndrome (40%) or
      autism (25%). Autosomal recessive congenital ichthyosis (ARCI) is genetically
      very heterogeneous and 8 different genes have been identified so far. The most
      frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200,
      000). Mutations in keratin genes are the cause of the keratinopathic ichthyoses,
      such as epidermolytic ichthyosis. They manifest at birth and often feature
      episodes of blistering. Most of these types are inherited as autosomal dominant
      traits, but autosomal recessive forms have also been described on occasion. 

PMID- 24119256
TI  - Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their
      toxicity assessment using differentiating Neuro-2a and embryonic fibroblast
      BALB/3T3.
AB  - BACKGROUND: Mushrooms are not only regarded as gourmet cuisine but also as
      therapeutic agent to promote cognition health. However, little toxicological
      information is available regarding their safety. Therefore, the aim of this study
      was to screen selected ethno-pharmacologically important mushrooms for
      stimulatory effects on neurite outgrowth and to test for any cytotoxicity.
      METHODS: The stimulatory effect of mushrooms on neurite outgrowth was assessed in
      differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured
      using Image-Pro Insight processor system. Neuritogenesis activity was further
      validated by fluorescence immunocytochemical staining of neurofilaments. In vitro
      cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and
      N2a cells for any embryo- and neuro-toxic effects; respectively. RESULTS: Aqueous
      extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and
      Grifola frondosa; as well as an ethanol extract of Cordyceps militaris
      significantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 +/-
      4.2%, 38.1 +/- 2.6%, 33.4 +/- 4.6%, 33.7 +/- 1.5%, and 35.8 +/- 3.4%;
      respectively. The IC50 values obtained from tetrazolium (MTT), neutral red uptake
      (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects
      following 24 h exposure of N2a and 3T3 cells to mushroom extracts. CONCLUSION:
      Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa
      and C. militaris may be developed as safe and healthy dietary supplements for
      brain and cognitive health.

PMID- 24119257
TI  - Transcriptome dynamics during fibre development in contrasting genotypes of
      Gossypium hirsutum L.
AB  - Understanding the contribution of genetic background in fibre quality traits is
      important for the development of future cotton varieties with superior fibre
      quality. We used Affymetrix microarray (Santa Clara, CA) and Roche 454 GSFLX
      (Branford, CT) for comparative transcriptome analysis between two superior and
      three inferior genotypes at six fibre developmental stages. Microarray-based
      analysis of variance (ANOVA) for 89 microarrays encompassing five contrasting
      genotypes and six developmental stages suggests that the stages of the fibre
      development have a more pronounced effect on the differentially expressed genes
      (DEGs) than the genetic background of genotypes. Superior genotypes showed
      enriched activity of cell wall enzymes, such as pectin methyl esterase, at early
      elongation stage, enriched metabolic activities such as lipid, amino acid and
      ribosomal protein subunits at peak elongation, and prolonged combinatorial
      regulation of brassinosteroid and auxin at later stages. Our efforts on
      transcriptome sequencing were focused on changes in gene expression at 25 DPA.
      Transcriptome sequencing resulted in the generation of 475 658 and 429 408 high
      quality reads from superior and inferior genotypes, respectively. A total of 24
      609 novel transcripts were identified manually for Gossypium hirsutum with no
      hits in NCBI 'nr' database. Gene ontology analyses showed that the genes for
      ribosome biogenesis, protein transport and fatty acid biosynthesis were over
      represented in superior genotype, whereas salt stress, abscisic acid stimuli and
      water deprivation leading to the increased proteolytic activity were more
      pronounced in inferior genotype.

PMID- 24119258
TI  - Efficacy of yttrium-90 synovectomy across a spectrum of arthropathies in an era
      of improved disease modifying drugs and treatment protocols.
AB  - AIM: To evaluate clinical response rates, duration of response and complication
      rates of yttrium radiosynovectomy (RSV) in an era of improved disease modifying
      antirheumatic drugs (DMARDS) and increased access to replacement therapy for
      clotting factor deficiencies introduced in the mid 2000s. METHODS: A
      retrospective review of 167 consecutive joints treated with RSV between 2000 and
      2010 was conducted. Clinical response and complication rates in 167 joints (119
      patients: 45 female,74 male, mean age 52 years) with rheumatoid, psoriatic,
      hemophilic, large joint mono-arthropathy and miscellaneous arthropathies
      refractory to conventional therapy were reviewed. Clinical response was
      determined at 3 months with responding patients reviewed again at 36 months to
      assess whether response was sustained. Comparison of response rates pre- and post
      introduction of improved DMARDS in the mid 2000s was also performed. RESULTS:
      Satisfactory clinical response was highest for large joint mono-arthropathy (85%)
      and lower for other arthropathies (47-64%). A strong relationship was
      demonstrated between degree and duration of response with 90% of complete
      responders compared to 41% of incomplete responders having a sustained response
      at 36 months (P <= 0.0001). Major complication rates were low (1%). No difference
      was demonstrated in response rates pre- and post-introduction of improved DMARDS
      in the mid 2000s. CONCLUSION: In an era of improved DMARDS, yttrium synovectomy
      remains a safe and effective procedure across a broad spectrum of arthropathies
      and should continue to be considered in cases refractory to conventional
      therapies. Complete responders can be expected to have symptom relief for at
      least 36 months and complication rates are low.

PMID- 24119259
TI  - Abdominal computed tomography, colonography and radiation exposure: what the
      surgeon needs to know.
AB  - AIM: Abdominal computed tomography (CT) improves the accuracy of clinical
      diagnosis and facilitates patient management. Radiation exposure must be
      considered by requesting clinicians and is especially relevant owing to the
      increasing use of CT colonography for diagnosis and screening of colorectal
      disorders. This review describes the radiation dose of abdominopelvic CT and
      colonography and attempts to quantify the risk for the clinician. METHOD:
      Articles were searched in the PubMed and Medline databases using combinations of
      the MeSH terms 'radiation', 'abdominal computed tomography' and 'colonography'.
      Electronic English language abstracts were read by two reviewers and the full
      article was retrieved if relevant to the review. RESULTS: Abdominopelvic CT and
      CT colonography convey significant radiation dose to the patient but also have
      considerable diagnostic potential. In the right clinical context, the radiation
      risk should not be overestimated. Techniques to reduce the dose should be used.
      Repeated imaging in certain patients is a concern and should be monitored.
      CONCLUSION: Radiation risk can be quantified and presented simply in a manner
      that both patients and doctors can comprehend and evaluate. This approach will
      diminish misconceptions and allow a rational choice of diagnostic test.

PMID- 24119260
TI  - Sociodemographic data collection for health equity measurement: a mixed methods
      study examining public opinions.
AB  - Monitoring inequalities in healthcare is increasingly being recognized as a key
      first step in providing equitable access to quality care. However, the detailed
      sociodemographic data that are necessary for monitoring are currently not
      routinely collected from patients in many jurisdictions. We undertook a mixed
      methods study to generate a more in-depth understanding of public opinion on the
      collection of patient sociodemographic information in healthcare settings for
      equity monitoring purposes in Ontario, Canada. The study included a provincial
      survey of 1,306 Ontarians, and in-depth interviews with a sample of 34
      individuals. Forty percent of survey participants disagreed that it was important
      for information to be collected in healthcare settings for equity monitoring.
      While there was a high level of support for the collection of language, a
      relatively large proportion of survey participants felt uncomfortable disclosing
      household income (67%), sexual orientation (40%) and educational background
      (38%). Variation in perceived importance and comfort with the collection of
      various types of information was observed among different survey participant
      subgroups. Many in-depth interview participants were also unsure of the
      importance of the collection of sociodemographic information in healthcare
      settings and expressed concerns related to potential discrimination and misuse of
      this information. Study findings highlight that there is considerable concern
      regarding disclosure of such information in healthcare settings among Ontarians
      and a lack of awareness of its purpose that may impede future collection of such
      information. These issues point to the need for increased education for the
      public on the purpose of sociodemographic data collection as a strategy to
      address this problem, and the use of data collection strategies that reduce
      discomfort with disclosure in healthcare settings. 

PMID- 24119261
TI  - EEG feature comparison and classification of simple and compound limb motor
      imagery.
AB  - BACKGROUND: Motor imagery can elicit brain oscillations in Rolandic mu rhythm and
      central beta rhythm, both originating in the sensorimotor cortex. In contrast
      with simple limb motor imagery, less work was reported about compound limb motor
      imagery which involves several parts of limbs. The goal of this study was to
      investigate the differences of the EEG patterns between simple limb motor imagery
      and compound limb motor imagery, and discuss the separability of multiple types
      of mental tasks. METHODS: Ten subjects participated in the experiment involving
      three tasks of simple limb motor imagery (left hand, right hand, feet), three
      tasks of compound limb motor imagery (both hands, left hand combined with right
      foot, right hand combined with left foot) and rest state. Event-related spectral
      perturbation (ERSP), power spectral entropy (PSE) and spatial distribution
      coefficient were adopted to analyze these seven EEG patterns. Then three
      algorithms of modified multi-class common spatial patterns (CSP) were used for
      feature extraction and classification was implemented by support vector machine
      (SVM). RESULTS: The induced event-related desynchronization (ERD) affects more
      components within both alpha and beta bands resulting in more broad ERD bands at
      electrode positions C3, Cz and C4 during left/right hand combined with
      contralateral foot imagery, whose PSE values are significant higher than that of
      simple limb motor imagery. From the topographical distribution, simultaneous
      imagination of upper limb and contralateral lower limb certainly contributes to
      the activation of more areas on cerebral cortex. Classification result shows that
      multi-class stationary Tikhonov regularized CSP (Multi-sTRCSP) outperforms other
      two multi-class CSP methods, with the highest accuracy of 84% and mean accuracy
      of 70%. CONCLUSIONS: The work implies that there exist the separable differences
      between simple limb motor imagery and compound limb motor imagery, which can be
      utilized to build a multimodal classification paradigm in motor imagery based
      brain-computer interface (BCI) systems.

PMID- 24119262
TI  - PPARgamma activation inhibits cerebral arteriogenesis in the hypoperfused rat
      brain.
AB  - AIMS: PPARgamma stimulation improves cardiovascular (CV) risk factors, but
      without improving overall clinical outcomes. PPARgamma agonists interfere with
      endothelial cell (EC), monocyte and smooth muscle cell (SMC) activation, function
      and proliferation, physiological processes critical for arterial collateral
      growth (arteriogenesis). We therefore assessed the effect of PPARgamma
      stimulation on cerebral adaptive and therapeutic collateral growth. METHODS: In a
      rat model of adaptive cerebral arteriogenesis (3-VO), collateral growth and
      function were assessed (i) in controls, (ii) after PPARgamma stimulation
      (pioglitazone 2.8 mg kg(-1); 10 mg kg(-1) compared with metformin 62.2 mg kg(-1)
      or sitagliptin 6.34 mg kg(-1)) for 21 days or (iii) after adding pioglitazone to
      G-CSF (40 MUg kg(-1) every other day) to induce therapeutic arteriogenesis for 1
      week. Pioglitazone effects on endothelial and SMC morphology and proliferation,
      monocyte activation and migration were studied. RESULTS: PPARgamma stimulation
      decreased cerebrovascular collateral growth and recovery of hemodynamic reserve
      capacity (CVRC controls: 12 +/- 7%; pio low: -2 +/- 9%; pio high: 1 +/- 7%;
      metformin: 9 +/- 13%; sitagliptin: 11 +/- 12%), counteracted G-CSF-induced
      therapeutic arteriogenesis and interfered with EC activation, SMC proliferation,
      monocyte activation and migration. CONCLUSION: Pharmacologic PPARgamma
      stimulation inhibits pro-arteriogenic EC activation, monocyte function, SMC
      proliferation and thus adaptive as well as G-CSF-induced cerebral arteriogenesis.
      Further studies should evaluate whether this effect may underlie the CV risk
      associated with thiazolidinedione use in patients.

PMID- 24119263
TI  - Discriminating plants using the DNA barcode rbcLb: an appraisal based on a large
      data set.
AB  - The ideal DNA barcode for plants remains to be discovered, and the candidate
      barcode rbcL has been met with considerable skepticism since its proposal. In
      fact, the variability within this gene has never been fully explored across all
      plant groups from algae to flowering plants, and its performance as a barcode has
      not been adequately tested. By analysing all of the rbcL sequences currently
      available in GenBank, we attempted to determine how well a region of rbcL
      performs as a barcode in species discrimination. We found that the rbcLb region
      was more variable than the frequently used rbcLa region. Both universal and plant
      group-specific primers were designed to amplify rbcLb, and the performance of
      rbcLa and rbcLb was tested in several ways. Using blast, both regions
      successfully identified all families and nearly all genera; however, the
      successful species identification rates varied significantly among plant groups,
      ranging from 24.58% to 85.50% for rbcLa and from 36.67% to 90.89% for rbcLb.
      Successful species discrimination ranged from 5.19% to 96.33% for rbcLa and from
      22.09% to 98.43% for rbcLb in species-rich families, and from 0 to 88.73% for
      rbcLa and from 2.04% to 100% for rbcLb in species-rich genera. Both regions
      performed better for lower plants than for higher plants, although rbcLb
      performed significantly better than rbcLa overall, particularly for angiosperms.
      Considering the applicability across plants, easy and unambiguous alignment, high
      primer universality, high sequence quality and high species discrimination power
      for lower plants, we suggest rbcLb as a universal plant barcode. 

PMID- 24119264
TI  - What do radiologists do all day? Quantifying workload and planning production in
      a medical imaging department.

PMID- 24119265
TI  - Comparison between incidental malignant and benign breast lesions detected by
      computed tomography: a systematic review.
AB  - INTRODUCTION: With increasing use of CT for a variety of diagnostic pathways,
      breast incidentalomas will be identified more frequently. Therefore, it is
      important for radiologists to know typical CT appearances of malignant and benign
      breast lesions. The aim of this study was to compare radiological features of
      benign and malignant incidental breast findings on CT reported in the literature.
      METHODS: A search for appropriate studies published between 1988 and 2012 yielded
      five results with a total of 214 patients/257 lesions. Morphological features of
      the described breast masses, such as shape, margins, enhancement, axillary
      lymphadenopathy and calcifications, were analysed. RESULTS: The prevalence of
      incidental breast carcinoma varied from 9.2% to 60.9% of the lesions. The
      frequency of benign lesions was 30.4-71.8%. The remaining incidental findings
      were intramammary metastases and primary or secondary breast lymphomas. Malignant
      lesions were larger in size, were round in shape and demonstrated a higher
      density compared with benign lesions. There was no significant difference in the
      margin characteristics of the masses between the groups. The morphological
      features previously postulated as typical for malignancy turned out to be non
      specific. CONCLUSIONS: Benign and malign breast incidentalomas are not safely
      distinguished from each other on standard chest CT. Therefore, all breast
      incidentalomas should be evaluated by further radiological/histological
      investigations.

PMID- 24119266
TI  - Pulmonary hamartomas: CT pixel analysis for fat attenuation using radiologic
      pathologic correlation.
AB  - INTRODUCTION: To assess the accuracy of CT pixel analysis for fat attenuation in
      pulmonary hamartomas. METHODS: Retrospective review identified 32 patients in
      three separate groups; pathologically proven hamartoma (n = 11), hamartoma
      diagnosed on imaging (n = 9) and a control group (n = 14) of pathology-proven non
      hamartomatous smoothly marginated solitary pulmonary nodules. All lesions were
      assessed using: visual assessment for fat, pixel analysis of the inner 2/3rds and
      mean attenuation of the entire lesion, using an internal reference for fat. Fat
      percentages on CT and at histology were compared. RESULTS: Visual assessment for
      macroscopic fat was the most reliable method for diagnosing pulmonary hamartoma.
      Combining percentage of fat-attenuation pixels in the inner 2/3rds of the lesion
      improved specificity to 100%. Mean attenuation or pixel analysis in isolation
      were not helpful in lesional characterization. CONCLUSION: Combining percentage
      fat-attenuating pixels in the inner 2/3rds with visual assessment for macroscopic
      fat improves specificity for diagnosing pulmonary hamartomas.

PMID- 24119267
TI  - Measuring and managing radiologist workload: application of lean and constraint
      theories and production planning principles to planning radiology services in a
      major tertiary hospital.
AB  - INTRODUCTION: We describe how techniques traditionally used in the manufacturing
      industry (lean management, the theory of constraints and production planning) can
      be applied to planning radiology services to reduce the impact of constraints
      such as limited radiologist hours, and to subsequently reduce delays in accessing
      imaging and in report turnaround. METHODS: Targets for imaging and reporting were
      set aligned with clinical needs. Capacity was quantified for each modality and
      for radiologists and recorded in activity lists. Demand was quantified and
      forecasting commenced based on historical referral rates. To try and mitigate the
      impact of radiologists as a constraint, lean management processes were applied to
      radiologist workflows. A production planning process was implemented. RESULTS:
      Outpatient waiting times to access imaging steadily decreased. Report turnaround
      times improved with the percentage of overnight/on-call reports completed by a
      1030 target time increased from approximately 30% to 80 to 90%. The percentage of
      emergency and inpatient reports completed within one hour increased from
      approximately 15% to approximately 50% with 80 to 90% available within 4 hours.
      The number of unreported cases on the radiologist work-list at the end of the
      working day reduced. The average weekly accuracy for demand forecasts for
      emergency and inpatient CT, MRI and plain film imaging was 91%, 83% and 92%
      respectively. For outpatient CT, MRI and plain film imaging the accuracy was 60%,
      55% and 77% respectively. Reliable routine weekly and medium to longer term
      service planning is now possible. CONCLUSIONS: Tools from industry can be
      successfully applied to diagnostic imaging services to improve performance. They
      allow an accurate understanding of the demands on a service, capacity, and can
      reliably predict the impact of changes in demand or capacity on service delivery.

PMID- 24119268
TI  - Measuring and managing radiologist workload: a method for quantifying radiologist
      activities and calculating the full-time equivalents required to operate a
      service.
AB  - INTRODUCTION: Accurate and transparent measurement and monitoring of radiologist
      workload is highly desirable for management of daily workflow in a radiology
      department, and for informing decisions on department staffing needs. It offers
      the potential for benchmarking between departments and assessing future national
      workforce and training requirements. We describe a technique for quantifying,
      with minimum subjectivity, all the work carried out by radiologists in a tertiary
      department. METHODS: Six broad categories of clinical activities contributing to
      radiologist workload were identified: reporting, procedures, trainee supervision,
      clinical conferences and teaching, informal case discussions, and administration
      related to referral forms. Time required for reporting was measured using data
      from the radiology information system. Other activities were measured by
      observation and timing by observers, and based on these results and extensive
      consultation, the time requirements and frequency of each activity was agreed on.
      An activity list was created to record this information and to calculate the
      total clinical hours required to meet the demand for radiologist services.
      RESULTS: Diagnostic reporting accounted for approximately 35% of radiologist
      clinical time; procedures, 23%; trainee supervision, 15%; conferences and
      tutorials, 14%; informal case discussions, 10%; and referral-related
      administration, 3%. The derived data have been proven reliable for workload
      planning over the past 3 years. CONCLUSIONS: A transparent and robust method of
      measuring radiologists' workload has been developed, with subjective assessments
      kept to a minimum. The technique has value for daily workload and longer term
      planning. It could be adapted for widespread use.

PMID- 24119269
TI  - Measuring and managing radiologist workload: measuring radiologist reporting
      times using data from a Radiology Information System.
AB  - INTRODUCTION: Historically, there has been no objective method of measuring the
      time required for radiologists to produce reports during normal work. We have
      created a technique for semi-automated measurement of radiologist reporting time,
      and through it produced a robust set of absolute time requirements and relative
      value units for consultant reporting of diagnostic examinations in our hospital.
      METHODS: A large sample of reporting times, recorded automatically by the
      Radiology Information System (COMRAD, Software Innovations, Christchurch, New
      Zealand) along with the description of each examination being reported, was
      placed in a database. Analysis was confined to diagnostic reporting by consultant
      radiologists. A spreadsheet was produced, listing the total number and the
      frequency of reporting times of each distinct examination. Outliers with
      exceptionally long report times (more than 10 min for plain radiography, 30 min
      for ultrasound, or 60 min for CT or MRI with some exceptions) were culled; this
      removed 9.5% of the total. Complex CTs requiring separate workstation time were
      assigned times by consensus. The median time for the remainder of each sample was
      the assigned absolute reporting time in minutes and seconds. Relative value units
      were calculated using the reporting time for a single view department chest X-ray
      of 1 min 38 s including verifying a report made using speech recognition
      software. RESULTS: A schedule of absolute and relative values, based on over 179
      000 reports, forms Table 2 of this paper. CONCLUSIONS: The technique provides a
      schedule of reporting times with reduced subjective input, which is more robust
      than existing systems for measuring reporting time.

PMID- 24119270
TI  - Comparison of positron emission tomography/CT and bremsstrahlung imaging
      following Y-90 radiation synovectomy.
AB  - INTRODUCTION: The aim of this study is to compare the results of positron
      emission tomography (PET)/CT with bremsstrahlung imaging following Y-90 radiation
      synovectomy. METHODS: All patients referred to our institution for Y-90 radiation
      synovectomy between July 2011 and February 2012 underwent both PET/CT and
      bremsstrahlung planar (+/- single photon emission computed tomography (SPECT) or
      SPECT/CT) imaging at 4 or 24 h following administration of Y-90 silicate colloid.
      PET image acquisition was performed for between 15 and 20 min. In patients who
      underwent SPECT, side-by-side comparison with PET was performed and image
      quality/resolution scored using a five-point scale. The distribution pattern of Y
      90 on PET and bremsstrahlung imaging was compared with the intra- or extra
      articular location of Y-90 activity on fused PET/CT. RESULTS: Thirteen joints (11
      knees and two ankles) were imaged with both PET/CT and planar bremsstrahlung
      imaging with 12 joints also imaged with bremsstrahlung SPECT. Of the 12 joints
      imaged with SPECT, PET image quality/resolution was superior in 11 and inferior
      in one. PET demonstrated a concordant distribution pattern compared with
      bremsstrahlung imaging in all scans, with the pattern classified as diffuse in 12
      and predominantly focal in one. In all 12 diffuse scans, PET/CT confirmed the Y
      90 activity to be located intra-articularly. In the one predominantly focal scan,
      the fused PET/CT images localised the Y-90 activity to mostly lie in the extra
      articular space of the knee. CONCLUSION: PET/CT can provide superior image
      quality compared with bremsstrahlung imaging and may enable reliable detection of
      extra-articular Y-90 activity when there are focal patterns on planar
      bremsstrahlung imaging.

PMID- 24119271
TI  - Computed tomographic colonography (CTC); colorectal cancer diagnosis with CTC in
      an Auckland population.
AB  - AIM: To determine the sensitivity of computed tomographic colonography (CTC) in
      the detection of colorectal cancer in our population and evaluate the reasons why
      these lesions may be missed on CTC. METHODS: All patients who underwent CTC in
      the 65-month period from 1 January 2004 to 1 July 2009 were included in the
      analysis. Demographic data and CTC findings were recorded, according to the CT
      Colonography Reporting and Data System. Data were cross-matched with the National
      Cancer Registry results for colorectal cancer cases between 1 January 2004 and 1
      October 2009, 3 months longer to include any delayed diagnoses. RESULTS: There
      were 2026 consecutive CTC patients, comprising 52.6% female, average age of 60
      years; range 19-87. Approximately 84% were symptomatic. There were 45 confirmed
      colorectal cancers among this patient group in the National Cancer Registry
      during the relevant time period compared with 43 suspected cancers on CTC, giving
      a miss rate of 2 of 45, or 4.4%. CONCLUSION: The sensitivity of 95% for CTC in
      the detection of colorectal cancer compares favourably with the published
      national and international data.

PMID- 24119272
TI  - Overview of airway involvement in tuberculosis.
AB  - Pulmonary tuberculosis is a ubiquitous infection and a re-emerging medical and
      socioeconomic problem resulting in increasing mortality and morbidity, especially
      in Asian countries. We aim to review the spectrum of imaging findings in airway
      involvement in tuberculosis through characteristic radiological images and to
      assess the role of computed tomography and image-guided interventions in the
      diagnosis and management of pulmonary tuberculosis. 

PMID- 24119273
TI  - CT and MRI appearances of cardiac pseudotumours.
AB  - Cardiac anatomic variants, vascular abnormalities and non-neoplastic mass lesions
      may be misinterpreted as tumours, potentially leading to inappropriate
      intervention. This article discusses the complementary role of multi-detector
      computed tomography and magnetic resonance imaging in the work-up of suspected
      masses. The cross-sectional imaging appearance of common or distinctive anatomic
      variants and pseudotumours, including 'don't touch' lesions, are reviewed. 

PMID- 24119275
TI  - Importance of mentoring in Australian radiology training.
AB  - Mentoring is widely accepted as a fundamental component of a number of
      professions; however, mentoring is underutilized, and its practice is poorly
      instituted in most Australian radiology training programmes. This article
      highlights the benefits of mentoring within the radiology training context.
      Potential barriers to successful mentoring are elucidated, and future pathways
      for improved implementation and application of mentor programmes with radiology
      training programmes are presented. 

PMID- 24119274
TI  - Mastoid pneumocoele with skull base and cervical spine pneumatisation.
AB  - Very uncommonly, Eustachian tube dysfunction can lead to symptomatic chronic
      elevation of middle ear pressure with aeration of bone and adjacent structures in
      the skull base and upper cervical spine, and an increased risk of fracture. We
      present a case demonstrating the natural history of this condition over 11 years
      before treatment and 10 months after treatment. 

PMID- 24119276
TI  - Can intensity-modulated radiation therapy spare the central flapped area while
      encompassing the target volume in radiotherapy after immediate breast
      reconstruction?
AB  - INTRODUCTION: Radiotherapy increases the morbidity of immediate breast
      reconstruction. To spare the flapped area without an adverse dose distribution of
      the target volume and organ at risks, various radiation techniques were assessed.
      METHODS: Twelve breasts undergoing skin-sparing mastectomy and immediate
      transverse rectus abdominis myocutaneous flap reconstruction were evaluated.
      After a delineation of whole breast, the doughnut-like breast target volume (BTV)
      including the chest wall and skin and the subtracted central flapped volume (FV)
      were defined. The opposed wedge tangential radiotherapy (3-dimensional conformal
      radiotherapy (3-D CRT) ), field-in-field radiotherapy (FiF), inverse intensity
      modulated radiotherapy (iIMRT), volumetric modulated arc radiotherapy (VMRT) and
      the mixture of FiF and iIMRT (HYBRID) were tried. Total 50 Gy was prescribed to
      the BTV. The paired student t-tests were performed. RESULTS: The V47.5Gy of the
      BTV was improved in iIMRT and VMRT compared with 3-D CRT and FiF. The mean FV
      doses in iIMRT and VMRT were 76.7 +/- 3.9% and 85.5 +/- 4.0%, respectively.
      However the mean ipsilateral lung doses were aggravated by iIMRT and VMRT. In
      terms of HYBRID, the V47.5Gy for the BTV was 97.5 +/- 0.7%. The mean FV dose was
      89.4 +/- 2.1%. While the mean FV dose in HYBRID was 13.7 +/- 2.1% (P < 0.001)
      lower than FiF, it was 12.8 +/- 1.9% (P < 0.001) higher than iIMRT. The mean
      ipsilateral lung dose in HYBRID was 2.8 +/- 1.9% (P < 0.001) worse than FiF, and
      2.6 +/- 1.8% (P < 0.001) better than iIMRT. CONCLUSIONS: The HYBRID could
      minimise the adverse dose distribution of lung and reduce 10% of the mean dose to
      the flapped area. For patients with adverse factors for the failure of breast
      reconstruction, the HYBRID could be considered.

PMID- 24119278
TI  - Patterns of retreatment with radiotherapy in a large academic centre.
AB  - AIMS: To characterise retreatment rates with radiotherapy at a large
      multifacility academic radiotherapy centre and assess the effect of distance on
      retreatment rate. MATERIALS AND METHODS: Electronic administrative records were
      reviewed for patients receiving radiotherapy between 1998 and 2010 at regional
      and metropolitan facilities. Course-level data were reconstructed from electronic
      administrative databases. Intent of therapy, treatment dates and diagnosis were
      available for analysis. Retreatment characteristics were derived, including
      proportion of patients receiving retreatment, proportion of total radiotherapy
      prescriptions dedicated to retreatment and retreatment per treating facility.
      Travel distance for each patient to their treatment centre was estimated, and
      retreatment rates were reported as a function of increasing distance. RESULTS: A
      total of 48 200 patients were treated with 66 277 treatment courses during the
      study period. Retreatment courses constituted 25.2% of all courses prescribed.
      During the study period, 20.4% of all patients received at least one treatment
      course. Of these, the average number of retreatment courses prescribed was 1.84.
      Patients treated with radical intent had a retreatment rate of 13% compared with
      45% for those treated initially with palliative intent. Retreatment rates in
      individual tumour sites ranged from 1.3 to 44.4%. The retreatment rate for those
      living less than 100 km from treatment facility was 24.8%, and 20.5% for those
      living more than 100 km from treatment centre (P < 0.001) CONCLUSION: Retreatment
      accounted for over one quarter of radiotherapy courses, with the rate influenced
      by casemix and follow-up duration. With increasing distance from treatment
      centre, a decrease in retreatment rate was observed.

PMID- 24119277
TI  - Can radiological changes in lymph node volume during treatment predict success of
      radiation therapy in patients with locally advanced head and neck squamous cell
      carcinoma?
AB  - BACKGROUND: Assessment of nodal response after radiotherapy (RT) for head and
      neck squamous cell carcinoma is difficult, as both CT and positron emission
      tomography scanning have limited predictive value for residual disease. We sought
      to measure changes in nodal volume during RT to determine whether such changes
      are predictive of nodal disease control. METHODS: Patients with locally advanced
      head and neck squamous cell carcinoma treated with 70 Gy of radical RT (+/
      chemotherapy or anti-epidermal growth factor receptor (EGFR) antibodies) were
      eligible. Baseline pre-RT scans and cone-beam CT scans done at the outset of
      treatment and at weeks 3, 5 and 7 (cone-beam CTs # 1, 2, 3 and 4, respectively)
      were deformably coregistered, and 3D nodal volumes were measured. RESULTS: Thirty
      eight eligible patients were identified. The main primary tumour site was
      oropharyngeal; most patients had stage IVa disease. Twenty-seven patients
      received concurrent platinum-based chemotherapy, 10 received only an EGFR
      inhibitor with RT and one received RT alone. Twelve patients had a failure in the
      neck. After week 1 of treatment, a 4% mean decrease in nodal volume was observed,
      increasing to 40% at week 7. Platinum-based chemotherapy achieved significantly
      greater decreases in nodal volume than EGFR inhibitors (44 vs. 25%; P = 0.026).
      Advanced tumour stage predicted neck failure (P = 0.002), but nodal volumes did
      not correlate with neck control. CONCLUSIONS: Changes in nodal volume are minimal
      initially during RT but accelerate during the latter weeks of therapy. This study
      suggests that chemotherapy achieves a greater decrease in nodal volume than EGFR
      inhibitors and that nodal changes do not predict disease control in the neck.

PMID- 24119279
TI  - Prospective single-arm study of intraoperative radiotherapy for locally advanced
      or recurrent rectal cancer.
AB  - INTRODUCTION: This study aims to evaluate the feasibility and outcomes of
      intraoperative radiotherapy (IORT) using high-dose-rate (HDR) brachytherapy for
      locally advanced or recurrent rectal cancers. Despite preoperative
      chemoradiation, patients with locally advanced or recurrent rectal cancers
      undergoing surgery remain at high risk of local recurrence. Intensification of
      radiation with IORT may improve local control. METHODS: This is a prospective non
      randomised study. Eligible patients were those with T4 rectal cancer or pelvic
      recurrence, deemed suitable for radical surgery but at high risk of positive
      resection margins, without evidence of metastasis. Chemoradiation was followed by
      radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator
      at time of surgery. RESULTS: There were 15% primary and 85% recurrent cancers.
      The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%,
      22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered
      patients (90% (95% confidence interval (CI) = 73-98) ) at a median reported time
      of 12 weeks (interquartile range (IQR) = 10-16) after chemoradiation. Mean IORT
      procedure and delivery times were 63 minutes (range 22-105 minutes). Ten patients
      (37% (95% CI = 19-58) ) experienced grade 3 or 4 toxicities (three wound, four
      abscesses, three soft tissue, three bowel obstructions, three ureteric
      obstructions and two sensory neuropathies). Local recurrence-free, failure-free
      and overall survival rates at 2.5 years were 68% (95% CI = 52-89), 37% (95% CI =
      23-61) and 82% (95% CI = 68-98), respectively. CONCLUSION: The addition of IORT
      to radical surgery for T4 or recurrent rectal cancer is feasible. It can be
      delivered safely with low morbidity and good tumour outcomes.

PMID- 24119280
TI  - The use of fiducial markers in image-guided radiotherapy for gastric cancer.
AB  - The use of fiducial markers (FM) in image-guided radiotherapy (IGRT) to increase
      treatment precision is emerging for upper gastrointestinal malignancies. To our
      knowledge there is no data beyond technical reports for the use of FMs in IGRT
      for gastric cancers in the current literature. We report a case of an 89-year old
      gentleman with localised gastric cancer who was deemed unfit for surgery and
      chemotherapy. He had FMs inserted endoscopically around the tumour via ultrasound
      guidance and received radiotherapy with a high-dose palliative intent via a two
      phase technique to 54 Gy in 30 fractions with IGRT. The use of FMs allowed
      confidence in tumour delineation and together with IGRT enabled precise and safe
      delivery of a higher dose. The patient tolerated the treatment without
      significant toxicity and had no evidence of residual or recurrent tumour 12
      months following radiotherapy. The use of FMs with IGRT in upper gastrointestinal
      malignancies warrants further collaborative studies. 

PMID- 24119282
TI  - Cumulative mitoxantrone-induced haematological and hepatic adverse effects in a
      subchronic in vivo study.
AB  - Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and
      haematotoxicity. This work aimed to investigate the occurrence of cumulative
      early and late MTX-induced hepatic and haematological disturbances in an vivo
      model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX
      at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia
      on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered
      euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An
      early immunosuppression with a drop in the IgG levels was observed, causing a
      slight decrease in the plasma total protein content. The early bone marrow
      depression was followed by signs of recovery in MTX48. The genotoxic potential of
      MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes.
      Increases in plasma iron and cholesterol levels in the MTX22 rats were observed,
      while in both groups increases in the unconjugated bilirubin, C4 complement, and
      decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase
      and transferrin were found in plasma samples. On MTX 48, the liver histology
      showed more hepatotoxic signs, the hepatic levels of reduced and oxidized
      glutathione were increased, and ATP hepatic levels were decreased. However, the
      hepatic total protein levels were decreased only in the livers of MTX22 group.
      Results demonstrated the MTX genotoxic effects, haemato- and direct
      hepatotoxicity. While the haematological toxicity is ameliorated with time, the
      same was not observed in the hepatic injury. 

PMID- 24119283
TI  - Identification of a type IV secretion substrate of Brucella abortus that
      participates in the early stages of intracellular survival.
AB  - Brucella abortus, the aetiological agent of bovine brucellosis, is an
      intracellular pathogen whose virulence is completely dependent on a type IV
      secretion system. This secretion system translocates effector proteins into the
      host cell to modulate the intracellular fate of the bacterium in order to
      establish a secure niche were it actively replicates. Although much has been done
      in understanding how this secretion system participates in the virulence process,
      few effector proteins have been identified to date. We describe here the
      identification of a type IV secretion substrate (SepA) that is only present in
      Brucella spp. and has no detectable homology to known proteins. This protein is
      secreted in a virB-dependent manner in a two-step process involving a periplasmic
      intermediate and secretion is necessary for its function. The deletion mutant
      showed a defect in the early stages of intracellular replication in professional
      and non-professional phagocytes although it invades the cells more efficiently
      than the wild-type parental strain. Our results indicate that, even though the
      mutant was more invasive, it had a defect in excluding the lysosomal marker Lamp
      1 and was inactivated more efficiently during the early phases of the
      intracellular life cycle. 

PMID- 24119284
TI  - Determining the role of sarcomeric proteins in facioscapulohumeral muscular
      dystrophy: a study protocol.
AB  - BACKGROUND: Although muscle weakness is a hallmark of facioscapulohumeral
      muscular dystrophy (FSHD), the molecular mechanisms that lead to weakness in FSHD
      remain largely unknown. Recent studies suggest aberrant expression of genes
      involved in skeletal muscle development and sarcomere contractility, and
      activation of pathways involved in sarcomeric protein degradation. This study
      will investigate the contribution of sarcomeric protein dysfunction to the
      pathogenesis of muscle weakness in FSHD. METHODS/DESIGN: Evaluation of sarcomeric
      function using skinned single muscle fiber contractile studies and protein
      analysis in muscle biopsies (quadriceps femoris and tibialis anterior) from
      patients with FSHD and age- and gender-matched healthy controls. Patients with
      other forms of muscular dystrophy and inflammatory myopathy will be included as
      disease controls to assess whether results are due to changes specific for FSHD,
      or a consequence of muscle disease in general. A total of 56 participants will be
      included. Extensive clinical parameters will be measured using MRI, quantitative
      muscle studies and physical activity assessments. DISCUSSION: This study is the
      first to extensively investigate muscle fiber physiology in FSHD following an
      earlier pilot study suggesting sarcomeric dysfunction in FSHD. The results
      obtained in this study will increase the understanding of the pathophysiology of
      muscle weakness in FSHD, and possibly identify novel targets for therapeutic
      intervention.

PMID- 24119285
TI  - Definition of a prospective payment system to reimburse emergency departments.
AB  - BACKGROUND: Payers are increasingly turning to Prospective Payment Systems (PPSs)
      because they incentivize efficiency, but their application to emergency
      departments (EDs) is difficult because of the high level of uncertainty and
      variability in the cost of treating each patient.To the best of our knowledge,
      our work represents the first attempt at defining a PPS for this part of hospital
      activity. METHODS: Data were specifically collected for this study and relate to
      1011 patients who were triaged at an ED of a major Italian hospital, during 1
      week in December 2010.The cost for each patient was analytically estimated by
      adding up several components: 1) physician and other staff costs that were
      imputed on the basis of the time each physician claimed to have spent treating
      the patient; 2) the cost for each test/treatment each patient actually underwent;
      3) overhead costs, shared among patients using the time elapsed between first
      examination and discharge from the ED. RESULTS: The distribution of costs by
      triage code shows that, although the average cost increases across the four
      triage groups, the variance within each code is quite high. The maximum cost for
      a yellow code is ?1074.7, compared with ?680 for red, the most serious code.
      Using cluster analysis, the red code cluster is enveloped by yellow, and their
      costs are therefore indistinguishable, while green codes span all cost groups.
      This suggests that triage code alone is not a good proxy for the patient cost,
      and that other cost drivers need to be included. CONCLUSIONS: Crude triage codes
      cannot be used to define PPSs because they are not sufficiently correlated with
      costs and are characterized by large variances. However, if combined with other
      information, such as the number of laboratory and non-laboratory
      tests/examinations, it is possible to define cost groups that are sufficiently
      homogeneous to be reimbursed prospectively. This should discourage strategic
      behavior and allow the ED to break even or create profits, which can be
      reinvested to improve services. The study provides health policy administrators
      with a new and feasible tool to implement prospective payment for EDs, and
      improve planning and cost control.

PMID- 24119286
TI  - Reply to 'What are ductal plate and ductal plate malformations of human livers?'.

PMID- 24119287
TI  - Dietary n-3 PUFA and CVD: a review of the evidence.
AB  - Many clinical and epidemiological studies have shown that the polyunsaturated n-3
      fatty acids EPA and DHA from fish and fish oils, provide cardiovascular
      protection, particularly in the setting of secondary prevention. n-3 Fatty acids
      beneficially influence a number of cardiometabolic risk factors including blood
      pressure, cardiac function, vascular reactivity and lipids, as well as having
      anti-platelet, anti-inflammatory and anti-oxidative actions. They do not appear
      to adversely interact with other medications such as statins and other lipid
      lowering drugs or antihypertensive medications. n-3 Fatty acids have gained
      widespread usage by general practitioners and clinicians in a number of clinical
      settings such as pregnancy and infant development, secondary prevention in CHD
      patients, treatment of dyslipidaemias and haemodialysis patients. Small doses are
      achievable with consumption of two to three oily fish meals per week or via
      purified encapsulated preparations now readily available. n-3 Fatty acids,
      particularly when consumed as fish, should be considered an important component
      of a healthy diet. The present paper reviews the effects of n-3 fatty acids on
      cardiometabolic risk factors, concentrating particularly on the evidence from
      randomised controlled studies in human subjects. 

PMID- 24119288
TI  - Sustained, neuron-specific IKK/NF-kappaB activation generates a selective
      neuroinflammatory response promoting local neurodegeneration with aging.
AB  - BACKGROUND: Increasing evidence indicates that neuroinflammation is a critical
      factor contributing to the progression of various neurodegenerative diseases. The
      IKK/NF-kappaB signalling system is a central regulator of inflammation, but it
      also affects neuronal survival and differentiation. A complex interplay between
      different CNS resident cells and infiltrating immune cells, which produce and
      respond to various inflammatory mediators, determines whether neuroinflammation
      is beneficial or detrimental. The IKK/NF-kappaB system is involved in both
      production of and responses to these mediators, although the precise contribution
      depends on the cell type as well as the cellular context, and is only partially
      understood. Here we investigated the specific contribution of neuronal IKK/NF
      kappaB signalling on the regulation of neuroinflammatory processes and its
      consequences. To address this issue, we established and analysed a conditional
      gain-of-function mouse model that expresses a constitutively active allele of
      IKK2 in principal forebrain neurons (IKK2nCA). Proinflammatory gene and growth
      factor expression, histopathology, microgliosis, astrogliosis, immune cell
      infiltration and spatial learning were assessed at different timepoints after
      persistent canonical IKK2/NF-kappaB activation. RESULTS: In contrast to other
      cell types and organ systems, chronic IKK2/NF-kappaB signalling in forebrain
      neurons of adult IKK2nCA animals did not cause a full-blown inflammatory response
      including infiltration of immune cells. Instead, we found a selective
      inflammatory response in the dentate gyrus characterized by astrogliosis,
      microgliosis and Tnf-alpha upregulation. Furthermore, downregulation of the
      neurotrophic factor Bdnf correlated with a selective and progressive atrophy of
      the dentate gyrus and a decline in hippocampus-dependent spatial learning.
      Neuronal degeneration was associated with increased Fluoro-jade staining, but
      lacked activation of apoptosis. Remarkably, neuronal loss could be partially
      reversed when chronic IKK2/NF-kappaB signalling was turned off and Bdnf
      expression was restored. CONCLUSION: Our results demonstrate that persistent
      IKK2/NF-kappaB signalling in forebrain neurons does not induce overall
      neuroinflammation, but elicits a selective inflammatory response in the dentate
      gyrus accompanied by decreased neuronal survival and impaired learning and
      memory. Our findings further suggest that chronic activation of neuronal IKK2/NF
      kappaB signalling, possibly as a consequence of neuroinflammatory conditions, is
      able to induce apoptosis-independent neurodegeneration via paracrine suppression
      of Bdnf synthesis.

PMID- 24119289
TI  - The identification of novel loci required for appropriate nodule development in
      Medicago truncatula.
AB  - BACKGROUND: The formation of functional symbiotic nodules is the result of a
      coordinated developmental program between legumes and rhizobial bacteria. Genetic
      analyses in legumes have been used to dissect the signaling processes required
      for establishing the legume-rhizobial endosymbiotic association. Compared to the
      early events of the symbiotic interaction, less attention has been paid to plant
      loci required for rhizobial colonization and the functioning of the nodule. Here
      we describe the identification and characterization of a number of new genetic
      loci in Medicago truncatula that are required for the development of effective
      nitrogen fixing nodules. RESULTS: Approximately 38,000 EMS and fast neutron
      mutagenized Medicago truncatula seedlings were screened for defects in symbiotic
      nitrogen fixation. Mutant plants impaired in nodule development and efficient
      nitrogen fixation were selected for further genetic and phenotypic analysis. Nine
      mutants completely lacking in nodule formation (Nod-) represented six
      complementation groups of which two novel loci have been identified. Eight
      mutants with ineffective nodules (Fix-) represented seven complementation groups,
      out of which five were new monogenic loci. The Fix- M. truncatula mutants showed
      symptoms of nitrogen deficiency and developed small white nodules. Microscopic
      analysis of Fix- nodules revealed that the mutants have defects in the release of
      rhizobia from infection threads, differentiation of rhizobia and maintenance of
      persistence of bacteria in nodule cells. Additionally, we monitored the
      transcriptional activity of symbiosis specific genes to define what
      transcriptional stage of the symbiotic process is blocked in each of the Fix-
      mutants. Based on the phenotypic and gene expression analysis a functional
      hierarchy of the FIX genes is proposed. CONCLUSIONS: The new symbiotic loci of M.
      truncatula isolated in this study provide the foundation for further
      characterization of the mechanisms underpinning nodulation, in particular the
      later stages associated with bacterial release and nodule function.

PMID- 24119290
TI  - Serum hepcidin levels are associated with serum triglycerides and interleukin-6
      concentrations in patients with end-stage renal disease.
AB  - Hepcidin has emerged as a peptide with a key role in the regulation of iron
      homeostasis in patients with chronic kidney disease (CKD), having a strong
      dependence on inflammation. Recent studies reveal that hepcidin may be also
      associated with the progression of atherosclerosis. This study was performed to
      analyze the relation of hepcidin to markers of atherosclerosis and inflammation
      in patients on dialysis. A total of 90 individuals were enrolled. Sixty patients
      with end-stage renal disease, who were on hemodialysis (HD) (N = 30) and
      peritoneal dialysis (N = 30) were compared with 30 normal controls (NC). Age,
      body mass index, time on dialysis, serum lipids, C-reactive protein (CRP) and
      interleukin-6 (IL-6) were measured and analyzed in correlation with hepcidin
      concentration. It was found that patients on HD and peritoneal dialysis have
      significantly higher (P < 0.0001) levels of hepcidin, CRP and IL-6 than NC.
      Hepcidin in dialysis patients is significantly related to age (r = 0.373, P =
      0.012), serum triglycerides (r = 0.401, P = 0.005), HDL-C (r = -0.268, P =
      0.048), CRP (r = 0.436, P = 0.0007) and IL-6 (r = 0.569, P < 0.0001). In multiple
      regression analysis, hepcidin correlated independently with triglycerides (beta =
      0.402, P = 0.041) and IL-6 (beta = 0.559, P = 0.006). Moreover, patients with
      high triglycerides in combination with high IL-6 levels have significantly
      increased concentrations of hepcidin than those with low triglycerides and low IL
      6 levels (P < 0.0001). Elevated levels of hepcidin in patients with CKD on
      dialysis may be related to the occurrence of high triglycerides and high IL-6
      serum concentrations. This probably suggests that hepcidin may play a role to the
      progression of atherosclerosis and inflammation, but this hypothesis should be
      further evaluated. 

PMID- 24119291
TI  - Design, synthesis and biological evaluation of pazopanib derivatives as antitumor
      agents.
AB  - A novel series of pazopanib derivatives were designed, synthesized, and evaluated
      for their inhibitory activity against a series of kinases including VEGFR-2,
      EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some
      compounds were also investigated. Compounds P2d and P2e demonstrated outstanding
      inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity
      compared with Pazopanib, the reference standard. These two compounds (P2d and
      P2e) could be used as novel lead compounds for further development of anticancer
      agents. 

PMID- 24119292
TI  - Protein S deficiency and Heerlen polymorphism in a Polish patient with acute
      myocardial infarction and previous venous thromboembolism.

PMID- 24119293
TI  - Joint aspiration of acute tense knee haemarthroses in adult haemophilia A
      patients.

PMID- 24119295
TI  - Differential recruitment of coregulators to the RORA promoter adds another layer
      of complexity to gene (dys) regulation by sex hormones in autism.
AB  - BACKGROUND: Our independent cohort studies have consistently shown the reduction
      of the nuclear receptor RORA (retinoic acid-related orphan receptor-alpha) in
      lymphoblasts as well as in brain tissues from individuals with autism spectrum
      disorder (ASD). Moreover, we have found that RORA regulates the gene for
      aromatase, which converts androgen to estrogen, and that male and female hormones
      regulate RORA in opposite directions, with androgen suppressing RORA, suggesting
      that the sexually dimorphic regulation of RORA may contribute to the male bias in
      ASD. However, the molecular mechanisms through which androgen and estrogen
      differentially regulate RORA are still unknown. METHODS: Here we use functional
      knockdown of hormone receptors and coregulators with small interfering RNA
      (siRNA) to investigate their involvement in sex hormone regulation of RORA in
      human neuronal cells. Luciferase assays using a vector containing various RORA
      promoter constructs were first performed to identify the promoter regions
      required for inverse regulation of RORA by male and female hormones. Sequential
      chromatin immunoprecipitation methods followed by quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR) analyses of RORA expression in
      hormone-treated SH-SY5Y cells were then utilized to identify coregulators that
      associate with hormone receptors on the RORA promoter. siRNA-mediated knockdown
      of interacting coregulators was performed followed by qRT-PCR analyses to confirm
      the functional requirement of each coregulator in hormone-regulated RORA
      expression. RESULTS: Our studies demonstrate the direct involvement of androgen
      receptor (AR) and estrogen receptor (ER) in the regulation of RORA by male and
      female hormones, respectively, and that the promoter region between -10055 bp and
      -2344 bp from the transcription start site of RORA is required for the inverse
      hormonal regulation. We further show that AR interacts with SUMO1, a reported
      suppressor of AR transcriptional activity, whereas ERalpha interacts with the
      coactivator NCOA5 on the RORA promoter. siRNA-mediated knockdown of SUMO1 and
      NCOA5 attenuate the sex hormone effects on RORA expression. CONCLUSIONS: AR and
      SUMO1 are involved in the suppression RORA expression by androgen, while ERalpha
      and NCOA5 collaborate in the up-regulation of RORA by estrogen. While this study
      offers a better understanding of molecular mechanisms involved in sex hormone
      regulation of RORA, it also reveals another layer of complexity with regard to
      gene regulation in ASD. Inasmuch as coregulators are capable of interacting with
      a multitude of transcription factors, aberrant expression of coregulator
      proteins, as we have seen previously in lymphoblasts from individuals with ASD,
      may contribute to the polygenic nature of gene dysregulation in ASD.

PMID- 24119296
TI  - Very good performance with bimodal stimulation in a like-hybrid modality in a
      patient with profound bilateral sensorineural hearing loss with low-frequencies
      preservation.
AB  - In this work we describe the experimental protocol set up to obtain very good
      results in speech performance and in time course, with a subject presenting
      profound bilateral sensorineural hearing loss with low-frequencies preservation.
      We used a bimodal stimulation with a like-hybrid modality. Auditory functions
      have been analyzed by standard tonal and speech audiometry tests, and verbal
      perception test. The fitting protocol permitted the subject to reach a perception
      at 65 dB of 100% in a very short time. The subject showed a sufficient recovery
      of the language spectral information and a good integration of verbal information
      with high consonantal recognition is present. This case report shows the
      importance to realize a correct cochlear implant fitting and that, in the case of
      bimodal stimulation, it is very important to obtain the mutual adjustment of the
      two hearing aids. Moreover, this study enhances the importance of realizing a
      preservative surgery to make the most of cochlear implants capacity.

PMID- 24119294
TI  - HPV-related cancers after solid organ transplantation in the United States.
AB  - Transplant recipients have elevated cancer risk including risk of human
      papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva
      and oropharynx. We examined the incidence of HPV-related cancers in 187 649 US
      recipients in the Transplant Cancer Match Study. Standardized incidence ratios
      (SIRs) compared incidence rates to the general population, and incidence rate
      ratios (IRRs) compared rates across transplant subgroups. We observed elevated
      incidence of HPV-related cancers (SIRs: in situ 3.3-20.3, invasive 2.2-7.3),
      except for invasive cervical cancer (SIR 1.0). Incidence increased with time
      since transplant for vulvar, anal and penile cancers (IRRs 2.1-4.6 for 5+ vs. <2
      years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13
      and increased incidence with B:44, contributed to susceptibility at several
      sites. Use of specific immunosuppressive medications was variably associated with
      incidence; for example, tacrolimus, was associated with reduced incidence for
      some anogenital cancers (IRRs 0.4-0.7) but increased incidence of oropharyngeal
      cancer (IRR 2.1). Thus, specific features associated with recipient
      characteristics, transplanted organs and medications are associated with
      incidence of HPV-related cancers after transplant. The absence of increased
      incidence of invasive cervical cancer highlights the success of cervical
      screening in this population and suggests a need for screening for other HPV
      related cancers.

PMID- 24119297
TI  - Nilotinib interferes with the signalling pathways implicated in acetaminophen
      hepatotoxicity.
AB  - Nilotinib, a second-generation tyrosine kinase inhibitor, has been recently
      approved for the treatment for chronic myeloid leukaemia. The objective of this
      study was to explore the potential effects of clinically relevant doses of
      nilotinib against acetaminophen (APAP)-induced hepatotoxicity in mice. To
      simulate the clinical application in human beings, nilotinib (25 and 50 mg/kg)
      was administered to mice 2 hr after APAP intoxication (500 mg/kg). The results
      indicated that nilotinib (25 mg/kg) (i) abolished APAP-induced liver injury and
      necro-inflammation, (ii) increased hepatic-reduced glutathione (GSH) and its
      related enzymes synthesis, (iii) suppressed hepatic oxidative/nitrosative stress
      cascades, (iv) decreased neutrophil accumulation in the liver, and (v) prevented
      the over-expression of B-cell lymphoma-2 (bcl-2), cyclin-D1 and stem cell factor
      receptor (c-Kit) proteins in the liver. Although nilotinib (50 mg/kg) acted
      through the same mechanisms, there was severe depletion in hepatic GSH content by
      nilotinib itself at that dose level, rather than the potent stimulation observed
      by using a dose of 25 mg/kg. Consequently, the mortality rate after 18 hr was
      100% for nilotinib (50 mg/kg) + APAP (750 mg/kg) versus 60% for APAP (750 mg/kg)
      and 40% for nilotinib (25 mg/kg) + APAP (750 mg/kg) in the survival analysis
      experiment. In conclusion, nilotinib can counteract the hepatotoxicity produced
      by a non-lethal dose of APAP. However, there is a risk of aggravating the
      mortality for a lethal dose of APAP when nilotinib is co-administered at doses
      relatively high, or near to the clinical range because of hepatic GSH depletion
      and c-kit inhibition.

PMID- 24119298
TI  - Human rhinoviruses and enteroviruses in influenza-like illness in Latin America.
AB  - BACKGROUND: Human rhinoviruses (HRVs) belong to the Picornaviridae family with
      high similarity to human enteroviruses (HEVs). Limited data is available from
      Latin America regarding the clinical presentation and strains of these viruses in
      respiratory disease. METHODS: We collected nasopharyngeal swabs at clinics
      located in eight Latin American countries from 3,375 subjects aged 25 years or
      younger who presented with influenza-like illness. RESULTS: Our subjects had a
      median age of 3 years and a 1.2:1.0 male:female ratio. HRV was identified in 16%
      and HEV was identified in 3%. HRVs accounted for a higher frequency of isolates
      in those of younger age, in particular children < 1 years old. HRV-C accounted
      for 38% of all HRVs detected. Phylogenetic analysis revealed a high proportion of
      recombinant strains between HRV-A/HRV-C and between HEV-A/HEV-B. In addition,
      both EV-D68 and EV-A71 were identified. CONCLUSIONS: In Latin America as in other
      regions, HRVs and HEVs account for a substantial proportion of respiratory
      viruses identified in young people with ILI, a finding that provides additional
      support for the development of pharmaceuticals and vaccines targeting these
      pathogens.

PMID- 24119300
TI  - Accuracy of allele frequency estimation using pooled RNA-Seq.
AB  - For nonmodel organisms, genome-wide information that describes functionally
      relevant variation may be obtained by RNA-Seq following de novo transcriptome
      assembly. While sequencing has become relatively inexpensive, the preparation of
      a large number of sequencing libraries remains prohibitively expensive for
      population genetic analyses of nonmodel species. Pooling samples may be then an
      attractive alternative. To test whether pooled RNA-Seq accurately predicts true
      allele frequencies, we analysed the liver transcriptomes of 10 bank voles. Each
      sample was sequenced both as an individually barcoded library and as a part of a
      pool. Equal amounts of total RNA from each vole were pooled prior to mRNA
      selection and library construction. Reads were mapped onto the de novo assembled
      reference transcriptome. High-quality genotypes for individual voles, determined
      for 23,682 SNPs, provided information on 'true' allele frequencies; allele
      frequencies estimated from the pool were then compared with these values. 'True'
      frequencies and those estimated from the pool were highly correlated. Mean
      relative estimation error was 21% and did not depend on expression level.
      However, we also observed a minor effect of interindividual variation in gene
      expression and allele-specific gene expression influencing allele frequency
      estimation accuracy. Moreover, we observed strong negative relationship between
      minor allele frequency and relative estimation error. Our results indicate that
      pooled RNA-Seq exhibits accuracy comparable with pooled genome resequencing, but
      variation in expression level between individuals should be assessed and
      accounted for. This should help in taking account the difference in accuracy
      between conservatively expressed transcripts and these which are variable in
      expression level.

PMID- 24119299
TI  - Antimicrobial resistance in human and animal pathogens in Zambia, Democratic
      Republic of Congo, Mozambique and Tanzania: an urgent need of a sustainable
      surveillance system.
AB  - A review of the published and unpublished literature on bacterial resistance in
      human and animals was performed. Sixty-eight articles/reports from the Democratic
      Republic of Congo (DRC), Mozambique, Tanzania and Zambia were reviewed. The
      majority of these articles were from Tanzania. There is an increasing trend in
      the incidence of antibiotic resistance; of major concern is the increase in
      multidrug- resistant Escherichia coli, Klebsiella pneumoniae, Staphylococcus
      aureus, Vibrio cholera, non-typhoid Salmonella and other pathogens responsible
      for nosocomial infections. The increase in methicillin- resistant Staphylococcus
      aureus and extended-spectrum beta-lactamase (ESBL) producers in the countries
      under review confirms the spread of these clones worldwide. Clinical microbiology
      services in these countries need to be strengthened in order to allow a
      coordinated surveillance for antimicrobial resistance and provide data for local
      treatment guidelines and for national policies to control antimicrobial
      resistance. While the present study does not provide conclusive evidence to
      associate the increasing trend in antibiotic resistance in humans with the use of
      antibiotics in animals, either as feed additives or veterinary prescription, we
      strongly recommend a one-health approach of systematic surveillance across the
      public and animal health sectors, as well as the adherence to the FAO (Food and
      Agriculture Organization)-OIE (World Organization of animal Health) -WHO(World
      Health Organization) recommendations for non-human antimicrobial usage. 

PMID- 24119301
TI  - Disease modifying therapies modulate cardiovascular risk factors in patients with
      multiple sclerosis.
AB  - OBJECTIVES: This retrospective study aimed to determine (1) the association
      between the use of three major disease modifying therapies (DMTs) (Interferon
      beta [IFN-beta], Glatiramer acetate [GA], Natalizumab [NTZ]) and cardiovascular
      (CV) risk factors in multiple sclerosis (MS) patients, and (2) the association
      between the use of CV drugs (antihypertensive, hypolipidemic, and antiplatelets)
      and other drugs acting on the CV system
      (antispastics/anticonvulsants/anxyolitics, antidepressants/stimulants), and MS
      disease severity. METHODS: The charts of 188 patients with MS, who were taking
      one of the three DMTs, and 110 patients, who were naive to these drugs, were
      retrospectively reviewed. The obtained data included height and weight, fasting
      lipid profiles, plasma glucose, systolic and diastolic BP, smoking habit, list of
      medications, and indicators of MS disease severity. RESULTS: The use of DMTs was
      associated with higher diastolic BP readings, as well as higher plasma glucose
      and HDL-C plasma levels. In addition, there was an association between CV risk
      factors and the type of DMTs. When compared to DMT-naive patients with MS, the
      use of IFN-beta and GA was associated with higher CV risk factors, whereas the
      use of NTZ was associated with lower CV risk factors. In DMT-naive patients, the
      use of CV and related drugs was associated with higher Extended Disability Status
      Scale (EDSS) and higher MS Severity Scale (MSSS). CONCLUSION: There is an
      association between higher CV risk factors and the use of DMTs. Furthermore, CV
      and related drugs have the potential for modulating MS disease severity.

PMID- 24119302
TI  - Mediation effect of perceived behavioural control on intended condom use:
      applicability of the theory of planned behaviour to money boys in China.
AB  - BACKGROUND: Money boys (MBs) are male sex workers who sell sex to men who have
      sex with men. The objectives of this study were to assess (a) the sexual HIV risk
      of MBs; (b) the ability of the theory of planned behaviour (TPB) to predict MBs'
      intentions to use condoms; and (c) the manner in which TPB constructs (attitudes
      towards condom use, subjective norms and perceived behavioural control) combine
      to influence condom use intentions. METHODS: Participants came from 10 MB
      frequented clubs in two cities in China. Multiple regression and path analytic
      models were used to test inter-relationships among the TPB constructs. RESULTS:
      Seventy-eight percent of the 122 MB participants reported having used condoms for
      every anal sex act. About one-third reported having had female sexual partners in
      the past 2 months; of these MBs, half (53%) used condoms for every sex act. A
      revised model using TPB constructs accounted for 52% of the variance of condom
      use intentions and revealed that perceived behavioural control was a mediator in
      pathways beginning with attitudes and ending with condom use intentions, and
      beginning with subjective norms and ending with intentions. CONCLUSIONS: The
      findings suggest that a revised model of TPB applies to condom use intentions
      among Chinese MBs. It may be appropriate to adapt HIV interventions that are
      grounded in TPB and that have been shown to be effective elsewhere for use with
      Chinese MBs. HIV interventions for this population should give perceived
      behavioural control and its predictors special consideration.

PMID- 24119303
TI  - The health outcomes and costs of people attending an interdisciplinary chronic
      disease service in regional Australia: protocol for a longitudinal cohort
      investigation.
AB  - BACKGROUND: Rates of chronic disease are escalating around the world. To date
      health service evaluations have focused on interventions for single chronic
      diseases. However, evaluations of the effectiveness of new intervention
      strategies that target single chronic diseases as well as multimorbidity are
      required, particularly in areas outside major metropolitan centres where access
      to services, such as specialist care, is difficult and where the retention and
      recruitment of health professionals affects service provision. METHODS: This
      study is a longitudinal investigation with a baseline and three follow-up
      assessments comparing the health and health costs of people with chronic disease
      before and after intervention at a chronic disease clinic, in regional Australia.
      The clinic is led by students under the supervision of health professionals. The
      study will provide preliminary evidence regarding the effectiveness of the
      intervention, and evaluate the influence of a range of factors on the health
      outcomes and costs of the patients attending the clinic. Patients will be
      evaluated at baseline (intake to the service), and at 3-, 6-, and 12-months after
      intake to the service. Health will be measured using the SF-36 and health costs
      will be measured using government and medical record sources. The intervention
      involves students and health professionals from multiple professions working
      together to treat patients with programs that include education and exercise
      therapy programs for back pain, and Healthy Lifestyle programs; as well as
      individual consultations involving single professions. DISCUSSION: Understanding
      the effect of a range of factors on the health state and health costs of people
      attending an interdisciplinary clinic will inform health service provision for
      this clinical group and will determine which factors need to be controlled for in
      future observational studies. Preliminary evidence regarding changes in health
      and health costs associated with the intervention will be a platform for future
      clinical trials of intervention effectiveness. The results will be of interest to
      teams investigating new chronic disease programs particularly for people with
      multimorbidity, and in areas outside major metropolitan centres. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Registry:
      ACTRN12611000724976.

PMID- 24119304
TI  - beta-cyclodextrin complex containing Lippia grata leaf essential oil reduces
      orofacial nociception in mice - evidence of possible involvement of descending
      inhibitory pain modulation pathway.
AB  - The treatment of orofacial pain remains a major challenge for modern medicine.
      Thus, we prepared and physicochemically characterized a new beta-cyclodextrin
      complex containing Lippia grata leaf essential oil (beta-CD/EO) to investigate
      their possible antinociceptive activity in animal models of orofacial pain. The
      results of Differential scanning calorimeter (DSC) and
      Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products
      prepared by Slurry complexation (SC) method were able to incorporate greater
      amounts of EO. In the X-ray diffractogram, it was shown that complex between EO
      and beta-CD was formed. Male Swiss mice were pre-treated with beta-CD/EO (6, 12
      or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle
      (distilled water, p.o.) 1 hr before treatment with formalin (20 MUL, 2%),
      capsaicin (20 MUL, 2.5 MUg) or glutamate (40 MUL, 25 MUM) into the right upper
      lip. Our results demonstrated that p.o. treatment with beta-CD/EO was
      significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face
      rubbing behaviour in both phases of the formalin test. beta-CD/EO-treated mice
      were also significantly (p < 0.05 or p < 0.001) protected against nociception
      induced by capsaicin and glutamate. For the action in the central nervous system
      (CNS), ninety minutes after the treatment, the mice were perfused, the brains
      collected, crioprotected, cut in a criostate and submitted to an
      immunofluorescence protocol for Fos protein. The immunofluorescence protocol
      demonstrated that the beta-CD/EO significantly activated (p < 0.05; p < 0.01 or p
      < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the
      periaqueductal gray of the CNS. These effects apparently did not alter, in tested
      doses, the motor coordination of mice in the rota-rod test. Our results proposed
      that beta-CD/EO might present an important draft of drug to the study of new
      compounds for the treatment of orofacial pain.

PMID- 24119305
TI  - MIA - A free and open source software for gray scale medical image analysis.
AB  - BACKGROUND: Gray scale images make the bulk of data in bio-medical image
      analysis, and hence, the main focus of many image processing tasks lies in the
      processing of these monochrome images. With ever improving acquisition devices,
      spatial and temporal image resolution increases, and data sets become very
      large.Various image processing frameworks exists that make the development of new
      algorithms easy by using high level programming languages or visual programming.
      These frameworks are also accessable to researchers that have no background or
      little in software development because they take care of otherwise complex tasks.
      Specifically, the management of working memory is taken care of automatically,
      usually at the price of requiring more it. As a result, processing large data
      sets with these tools becomes increasingly difficult on work station class
      computers.One alternative to using these high level processing tools is the
      development of new algorithms in a languages like C++, that gives the developer
      full control over how memory is handled, but the resulting workflow for the
      prototyping of new algorithms is rather time intensive, and also not appropriate
      for a researcher with little or no knowledge in software development.Another
      alternative is in using command line tools that run image processing tasks, use
      the hard disk to store intermediate results, and provide automation by using
      shell scripts. Although not as convenient as, e.g. visual programming, this
      approach is still accessable to researchers without a background in computer
      science. However, only few tools exist that provide this kind of processing
      interface, they are usually quite task specific, and don't provide an clear
      approach when one wants to shape a new command line tool from a prototype shell
      script. RESULTS: The proposed framework, MIA, provides a combination of command
      line tools, plug-ins, and libraries that make it possible to run image processing
      tasks interactively in a command shell and to prototype by using the according
      shell scripting language. Since the hard disk becomes the temporal storage memory
      management is usually a non-issue in the prototyping phase. By using string-based
      descriptions for filters, optimizers, and the likes, the transition from shell
      scripts to full fledged programs implemented in C++ is also made easy. In
      addition, its design based on atomic plug-ins and single tasks command line tools
      makes it easy to extend MIA, usually without the requirement to touch or
      recompile existing code. CONCLUSION: In this article, we describe the general
      design of MIA, a general purpouse framework for gray scale image processing. We
      demonstrated the applicability of the software with example applications from
      three different research scenarios, namely motion compensation in myocardial
      perfusion imaging, the processing of high resolution image data that arises in
      virtual anthropology, and retrospective analysis of treatment outcome in
      orthognathic surgery. With MIA prototyping algorithms by using shell scripts that
      combine small, single-task command line tools is a viable alternative to the use
      of high level languages, an approach that is especially useful when large data
      sets need to be processed.

PMID- 24119306
TI  - Trigger medications and patient-related risk factors for Parkinson disease
      psychosis requiring anti-psychotic drugs: a retrospective cohort study.
AB  - BACKGROUND: Psychoses such as hallucinations are a frequent non-motor problem in
      patients with Parkinson disease (PD) and serious psychosis requires anti
      psychotic medications that worsen Parkinsonism. Although psychosis could be
      associated with patient-related or biological factors such as cognition, age, and
      severity of PD, it can also be associated with medications.Therefore we aimed to
      investigate patient-related and medication-related risks of psychosis requiring
      anti-psychotic medications (serious psychosis). METHODS: A retrospective cohort
      of 331 PD patients was followed for 2 years. Patient-related factors associated
      with risk of psychosis were identified by a survival time analysis. In patients
      who developed psychosis, medications during the hazard period (1-14 days before
      psychosis) were contrasted with those during the control periods (1 and 3 months
      before psychosis) using a case-crossover analysis to identify medication-related
      risks of psychosis. RESULTS: Serious psychosis was detected in 52 patients and
      the incidence was estimated to be 116 (95% confidence interval [CI], 85-148) per
      1,000 person-years. Analyses of baseline characteristics revealed the risk to be
      higher in patients with a modified Hoehn-Yahr stage of >=4 (hazard ratio [HR],
      2.22; 95% CI, 1.11-4.40), those with a longer duration of PD (HR, 1.25; 95% CI,
      1.00-1.55, per 5 years) and those with Mini-Mental State Examination scores of
      <=24 (HR, 2.66; 95% CI, 1.37-5.16). The case-crossover analysis revealed that
      anti-cholinergics use (HR, 19.7; 95% CI, 2.39-162) elevated the risk, while
      donepezil use reduced it (HR, 0.48; 95% CI, 0.27-0.85). CONCLUSIONS: Risk of
      psychosis was elevated by increasing severity of PD, cognitive dysfunction and
      duration of the disease. It was elevated by use of anti-cholinergic drugs and
      reduced by use of donepezil. The medication-related risk was higher in patients
      aged >= 70 years. In contrast, there was no significant medication-related risk
      in younger patients, suggesting different pathomechanisms between young and old
      patients.

PMID- 24119307
TI  - Iron deprivation results in a rapid but not sustained increase of the expression
      of genes involved in iron metabolism and sulfate uptake in tomato (Solanum
      lycopersicum L.) seedlings.
AB  - Characterization of the relationship between sulfur and iron in both Strategy I
      and Strategy II plants, has proven that low sulfur availability often limits
      plant capability to cope with iron shortage. Here it was investigated whether the
      adaptation to iron deficiency in tomato (Solanum lycopersicum L.) plants was
      associated with an increased root sulfate uptake and translocation capacity, and
      modified dynamics of total sulfur and thiols accumulation between roots and
      shoots. Most of the tomato sulfate transporter genes belonging to Groups 1, 2,
      and 4 were significantly upregulated in iron-deficient roots, as it commonly
      occurs under S-deficient conditions. The upregulation of the two high affinity
      sulfate transporter genes, SlST1.1 and SlST1.2, by iron deprivation clearly
      suggests an increased root capability to take up sulfate. Furthermore, the
      upregulation of the two low affinity sulfate transporter genes SlST2.1 and
      SlST4.1 in iron-deficient roots, accompanied by a substantial accumulation of
      total sulfur and thiols in shoots of iron-starved plants, likely supports an
      increased root-to-shoot translocation of sulfate. Results suggest that tomato
      plants exposed to iron-deficiency are able to change sulfur metabolic balance
      mimicking sulfur starvation responses to meet the increased demand for methionine
      and its derivatives, allowing them to cope with this stress. 

PMID- 24119310
TI  - Development of a data collection tool to profile osteopathic practice: use of a
      nominal group technique to enhance clinician involvement.
AB  - INTRODUCTION: Little is known about the profile of osteopathic care in the United
      Kingdom (UK). To address this, a standardised data collection (SDC) tool was
      developed to record patient-based data within private practice. METHODS: The
      development of the SDC tool took place within a national network of research
      groups (hubs) created by the National Council for Osteopathic Research (NCOR);
      nominal groups were created from the hub network. A Nominal Group Technique (NGT)
      was used to promote maximum involvement by clinicians and increase ownership of
      the process: this approach encouraged generation of ideas around specific topics.
      Following several rounds of iteration, a draft tool was created, followed by a
      three stage testing process to identify omissions, unnecessary jargon,
      ambiguities, and any regional differences. RESULTS: The tool developed for a
      national use by UK osteopaths consisted of 65 items. These were divided into
      specific sections for patient or clinician completion. The section for patient
      completion collected data concerning demographic and symptom data. Clinicians
      provided data concerning treatment provided, advice to promote self-management
      and avoidance of symptom recurrence, outcome information, service data concerned
      with waiting times, the number of treatments delivered, and the necessity for
      referral. CONCLUSION: The tool development process produced a data collection
      tool aimed to collect snapshot data across the osteopathic profession. The
      national pilot of the tool will identify changes required, and any barriers to
      its use by busy professionals.

PMID- 24119309
TI  - The addition of whole soy flour to cafeteria diet reduces metabolic risk markers
      in wistar rats.
AB  - BACKGROUND: Soybean is termed a functional food because it contains bioactive
      compounds. However, its effects are not well known under unbalanced diet
      conditions. This work is aimed at evaluating the effect of adding whole soy flour
      to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity
      markers in rats. METHODS: In this study, 30 male adult Wistar rats were used,
      distributed among three groups (n = 10): AIN-93 M diet, cafeteria diet (CAF) and
      cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were
      measured: food intake; weight gain; serum concentrations of triglycerides, total
      cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine
      (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS);
      humidity and lipid fecal content; weight and fat of the liver. The villous
      height, the crypt depth and the thickness of the duodenal and ileal circular and
      longitudinal muscle layers of the animals were also measured. RESULTS: There was
      a significant reduction in the food intake in the CAF group. The CAFS showed
      lower serum concentrations of triglycerides and serum TBARS and a lower
      percentage of hepatic fat, with a corresponding increase in thickness of the
      intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid
      excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c
      and villous height. The addition of soy did not promote any change in these
      parameters. CONCLUSIONS: The inclusion of whole soy flour in a high-fat diet may
      be helpful in reducing some markers of metabolic risk; however, more studies are
      required to clarify its effects on unbalanced diets.

PMID- 24119311
TI  - Towards a predictive model to assess the natural position of the Posidonia
      oceanica seagrass meadows upper limit.
AB  - The upper portion of the meadows of the protected Mediterranean seagrass
      Posidonia oceanica occurs in the region of the seafloor mostly affected by surf
      related effects. Evaluation of its status is part of monitoring programs, but
      proper conclusions are difficult to draw due to the lack of definite reference
      conditions. Comparing the position of the meadow upper limit with the beach
      morphodynamics (i.e. the distinctive type of beach produced by topography and
      wave climate) provided evidence that the natural landwards extension of meadows
      can be predicted. An innovative model was therefore developed in order to locate
      the region of the seafloor where the meadow upper limit should lie in natural
      conditions (i.e. those governed only by hydrodynamics, in absence of significant
      anthropogenic impact). This predictive model was validated in additional sites,
      which showed perfect agreement between predictions and observations. This makes
      the model a valuable tool for coastal management. 

PMID- 24119308
TI  - Antioxidant properties of xanthones from Calophyllum brasiliense: prevention of
      oxidative damage induced by FeSO4.
AB  - BACKGROUND: Reactive oxygen species (ROS) are important mediators in a number of
      degenerative diseases. Oxidative stress refers to the imbalance between the
      production of ROS and the ability to scavenge these species through endogenous
      antioxidant systems. Since antioxidants can inhibit oxidative processes, it
      becomes relevant to describe natural compounds with antioxidant properties which
      may be designed as therapies to decrease oxidative damage and stimulate
      endogenous cytoprotective systems. The present study tested the protective effect
      of two xanthones isolated from the heartwood of Calophyllum brasilienses against
      FeSO4-induced toxicity. METHODS: Through combinatory chemistry assays, we
      evaluated the superoxide (O2.-), hydroxyl radical (OH.), hydrogen peroxide (H2O2)
      and peroxynitrite (ONO-) scavenging capacity of jacareubin (xanthone III) and 2
      (3,3-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone (xanthone V). The effect of
      these xanthones on murine DNA and bovine serum albumin degradation induced by an
      OH. generator system was also evaluated. Additionally, we investigated the effect
      of these xanthones on ROS production, lipid peroxidation and glutathione
      reductase (GR) activity in FeSO4-exposed brain, liver and lung rat homogenates.
      RESULTS: Xanthone V exhibited a better scavenging capacity for O2.-, ONOO- and
      OH. than xanthone III, although both xanthones were unable to trap H2O2.
      Additionally, xanthones III and V prevented the albumin and DNA degradation
      induced by the OH. generator system. Lipid peroxidation and ROS production evoked
      by FeSO4 were decreased by both xanthones in all tissues tested. Xanthones III
      and V also prevented the GR activity depletion induced by pro-oxidant activity
      only in the brain. CONCLUSIONS: Altogether, the collected evidence suggests that
      xanthones can play a role as potential agents to attenuate the oxidative damage
      produced by different pro-oxidants.

PMID- 24119312
TI  - Legacy contaminant bioaccumulation in rock crabs in Sydney Harbour during
      remediation of the Sydney Tar Ponds, Nova Scotia, Canada.
AB  - Concentrations of PAHs, PCBs, metals and lipids in hepatopancreas of rock crabs
      (Cancer irroratus) were measured in Sydney Harbour (SH) for one year prior to
      remediation and three years of remediation of the Sydney Tar Ponds (STP), Nova
      Scotia. Low level concentrations of PCBs and metals were measured, although PAHs
      were mostly undetected. Metal concentrations showed little spatio-temporal
      variability, although highest concentrations of As, Cd and Cu were measured at
      reference stations furthest from the STP remediation site. Mercury concentrations
      were at least an order of magnitude lower than Canadian guidelines. Moderately
      elevated PCB concentrations were detected in crabs near Muggah Creek, but these
      were generally not higher than those measured during baseline. Despite
      remediation activities, current contaminant burdens measured in crabs were much
      lower than previously reported in other studies of crabs and lobster in
      industrial harbours in eastern Canada, due in part to natural recovery of SH
      sediments. 

PMID- 24119314
TI  - Electron channeling contrast imaging of plastic deformation induced by
      indentation in polycrystalline nickel.
AB  - Vickers microindentation and Berkovich nanoindentation tests were carried out on
      a polycrystalline nickel (Ni) bulk specimen. Electron channeling contrast imaging
      (ECCI) in conjunction with electron backscattered diffraction was used to image
      and characterize plastic deformation inside and around the indents using a field
      emission scanning electron microscope. The ECCI was performed with a 5 keV beam
      energy and 0 degrees  tilt specimen position. The strain field distribution, slip
      lines, and Taylor lattices were imaged on an indented surface. Orientation
      mapping was used to investigate the local crystallographic misorientation and
      identify specific ?110? slip systems. An ion milling surface preparation
      technique was used to remove materials from the surface which permitted the study
      of deformed microstructure below the indent. A dislocation density of 1011 cm-2
      was calculated based on the curvature of bend contours observed in the ECCI
      micrographs obtained from the Vickers indents. A yield strength of 500 MPa was
      calculated based on the size of the strain field measured from the ECCI
      micrographs of the nanoindents. The combination of ion milling, ECCI, and
      electron backscattered diffraction was shown to be beneficial to investigate the
      indentation-induced plastic deformation in a polycrystalline Ni bulk specimen. 

PMID- 24119313
TI  - Historical pattern and mass balance of trace metals in sediments of the
      northwestern Adriatic Sea Shelf.
AB  - In view of the recent action in Marine Strategy Framework Directive,
      reconstructing the history of anthropogenic metal inputs and calculating the
      budgets for the northwestern part of the Italian Adriatic basin can provide a
      benchmark for comparison with new evidences and enlighten recent environmental
      changes. Among the metals, the attention was focused on Pb and Zn, as they
      provide the most significant anthropogenic signals. In 1988, areal distributions
      clearly identified the Po, Adige and Brenta rivers as the main sources of
      contaminants. The study area was divided in three compartments. The area in front
      of the Po delta represented a sink for metals but the accumulation of Zn and Pb
      integrated over the entire study area suggests an effective export throughout
      southern boundary. Most concentration-depth/year profiles in cores showed an
      upward increase from the Italian Unification (1861), with a still significant
      anthropogenic supply at the time of sampling. 

PMID- 24119315
TI  - Anti-Mullerian hormone may regulate the number of calbindin-positive neurons in
      the sexually dimorphic nucleus of the preoptic area of male mice.
AB  - BACKGROUND: The male brain is putatively organised early in development by
      testosterone, with the sexually dimorphic nucleus of the medial preoptic area
      (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the
      rat SDN, and the immature testes secrete anti-Mullerian hormone (AMH) as well as
      testosterone. We have therefore re-examined the development of the murine SDN to
      determine whether it is influenced by AMH and/or whether the number of calbindin
      positive (calbindin+ve) neurons in it changes after pre-pubescent development.
      METHODS: In mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN).
      The number and size of the neurons in the CALB-SDN of male and female AMH null
      mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using
      stereological techniques. Groups of mice were examined immediately before the
      onset of puberty (20 days postnatal) and at adulthood (129-147 days old).
      RESULTS: The wild-type pre-pubertal male mice had 47% more calbindin+ve neurons
      in the CALB-SDN than their female wild-type littermates. This sex difference was
      entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost
      doubled due to a net reduction in the number and size of calbindin+ve neurons in
      females and a net increase in neuron number in males. These changes occurred to a
      similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of
      calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+
      males and Amh+/+ females. The sex difference in the size of the neurons was
      predominantly generated by a female-specific atrophy after 20 days, independent
      of AMH. CONCLUSIONS: The establishment of dimorphic cell number in the CALB-SDN
      of mice is biphasic, with each phase being subject to different regulation. The
      second phase of dimorphism is not dependent on the first phase having occurred as
      it was present in the Amh-/- male mice that have female-like numbers of
      calbindin+ve neurons at 20 days. These observations extend emerging evidence that
      the organisation of highly dimorphic neuronal networks changes during puberty or
      afterwards. They also raise the possibility that cellular events attributed to
      the imprinting effects of testosterone are mediated by AMH.

PMID- 24119316
TI  - A positive surgical margin following radical prostatectomy should not routinely
      be the indication for adjuvant radiation therapy.

PMID- 24119317
TI  - Different pyeloplasty approaches, similar excellent results.

PMID- 24119318
TI  - Lifestyle changes for improving disease-specific quality of life in sedentary men
      on long-term androgen-deprivation therapy for advanced prostate cancer: a
      randomised controlled trial.
AB  - BACKGROUND: Prostate cancer is a key driver of cancer-related global disability
      adjusted life-years. Androgen-deprivation therapy (ADT) for advanced disease is
      linked to fatigue, reduced physical function, and quality of life (QoL).
      OBJECTIVE: To evaluate the effect of a lifestyle intervention on disease-specific
      QoL, diastolic blood pressure, and cancer-related fatigue in sedentary men
      receiving long-term ADT for advanced prostate cancer. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 100 hundred sedentary men with locally advanced or
      metastatic prostate cancer on long-term ADT were randomised to an intervention or
      usual care group. INTERVENTION: A 12-wk lifestyle intervention consisting of
      aerobic and resistance exercise with parallel dietary advice. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Disease-specific QoL was measured using
      the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Functional
      Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaires at 12 wk
      postintervention and at 6 mo following withdrawal of support. Analysis of
      covariance and mixed regression were conducted. RESULTS AND LIMITATIONS:
      Clinically relevant improvements in FACT-P were seen at 12 wk in the intervention
      group compared with controls (mean difference: 8.9 points; 95% confidence
      interval [CI], 3.7-14.2; adjusted p=0.001). No difference was apparent at 6 mo
      (mean difference: 3.3 points; 95% CI, -2.6 to 9.3; adjusted p=0.27). No
      difference in diastolic blood pressure was seen at either follow-up (all p >
      0.05). Clinically relevant improvements in FACT-F were seen at 12 wk (mean
      difference: 5.3 points; 95% CI, 2.7-7.9; adjusted p<0.001) and maintained
      following withdrawal of supervision (mean difference: 3.9 points; 95% CI, 1.1
      6.8; adjusted p=0.007). Improvements in exercise tolerance and behaviour were
      maintained at 6 mo (adjusted p<0.001 and 0.038). CONCLUSIONS: A lifestyle
      intervention resulted in a clinically meaningful improvement in disease-specific
      QoL that was not maintained postintervention. No effect on blood pressure
      occurred. Durability of response was seen in fatigue and exercise behaviour.
      Further evaluation of support structures is essential. TRIAL REGISTRATION:
      ISRCTN88605738.

PMID- 24119319
TI  - Tadalafil once daily in men with erectile dysfunction: an integrated analysis of
      data obtained from 1913 patients from six randomized, double-blind, placebo
      controlled, clinical studies.
AB  - BACKGROUND: This analysis explores tadalafil once-daily treatment for 12 wk in
      clinical subpopulations of men with erectile dysfunction (ED). OBJECTIVE: Assess
      the efficacy and safety of once-daily tadalafil 2.5mg and 5mg in patients with
      different ED characteristics and comorbidities. DESIGN, SETTING, AND
      PARTICIPANTS: This analysis integrated data from six randomized, double-blind,
      placebo-controlled studies that assigned 1913 men with >=3-mo history of ED
      either to once-daily placebo (n=596), tadalafil 2.5mg (n=394), or tadalafil 5mg
      (n=923). Clinical factors examined included: ethnicity, age, obesity, alcohol
      consumption, smoking, comorbidities, concomitant medication, and ED
      characteristics (etiology, duration, severity). OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Descriptive statistics were reported for efficacy and
      safety, including International Index of Erectile Function Erectile Function
      Domain (IIEF-EF) scores and Sexual Encounter Profile question 3 (SEP3) responses.
      Clinical factors were included in analysis of covariance models using last
      observation carried forward for SEP3 and IIEF-EF scores. RESULTS AND LIMITATIONS:
      Both tadalafil doses significantly improved SEP3 responses (least-squares [LS]
      mean change: 17.8% and 23.6%, respectively) and IIEF-EF scores (LS mean change:
      4.2; 5.4) compared with placebo (p<0.01). Treatment with 2.5mg and 5mg tadalafil
      resulted in IIEF-EF LS mean improvements >=4 (minimal clinically important
      difference [MCID]) in patients with hypertension (4.3 [95% confidence interval
      (CI), 2.9-5.7]; 4.7 [95% CI, 3.5-5.8]), cardiac disorder (7.0 [95% CI, 4.7-9.3];
      6.3 [95% CI, 4.4-8.2]), or hyperlipidemia (5.3 [95% CI, 3.4-7.1]; 5.8 [95% CI,
      4.3-7.4]). Obese patients (4.7 [95% CI, 3.4-6.0]), smokers (4.8 [95% CI, 3.0
      6.7]), and psychogenic ED (7.3 [95% CI, 5.0-9.6]) reached MCID only after
      treatment with 5mg tadalafil. Severity-specific MCID (IIEF-EF change >=7) was
      achieved by 44.5% of patients with severe baseline ED treated with tadalafil 5mg,
      compared with 11.6% of placebo-treated patients. No unexpected safety findings
      were observed. These analyses were performed on integrated data and can only
      provide descriptive results to guide further investigations. CONCLUSIONS:
      Treatment with tadalafil 2.5mg or 5mg once daily was well tolerated and resulted
      in clinically important improvements in patients with mild (54.3% and 74.8%,
      respectively), moderate (51.3% and 63.1%, respectively), or severe (33.7% and
      44.5%, respectively) ED.

PMID- 24119320
TI  - Lack of identification of Flaviviruses in oral and cloacal swabs from long- and
      short-distance migratory birds in Trentino-Alto Adige (North-eastern Italy).
AB  - BACKGROUND: West Nile virus (WNV) and Usutu virus (USUV), both belonging to the
      genus Flavivirus, are emerging in Italy as important human and animal pathogens.
      Migratory birds are involved in the spread of Flaviviruses over long distances,
      particularly from Africa to Europe. Once introduced, these viruses can be further
      be dispersed by short-distance migratory and resident bird species. Thus far,
      there is still a considerable knowledge gap on the role played by different bird
      species in the ecology and transmission mechanisms of these viruses. The Region
      of Trentino-Alto Adige (north-eastern Italy) is located on the migratory route of
      many of the short- and long-distance migratory birds that cross the Alps,
      connecting northern Europe and western Asia with southern Europe and Africa.
      Until now, only a silent circulation of WNV and USUV within the territory of the
      Province of Trento has been confirmed by serological screening, whilst no cases
      of infected humans or animals have so far been reported. However, continuous
      spillover events of both viruses have been reported in neighbouring Regions. The
      aim of this study was to monitor the circulation of WNV and USUV in Trentino-Alto
      Adige, in order to detect if active virus shedding occurs in migratory birds
      captured during their seasonal movements and to evaluate the role that different
      bird species could play in the spreading of these viruses. METHODS: We carried
      out a biomolecular survey on oral and cloacal swabs collected from migratory
      birds during seasonal migrations. Birds belonging to 18 transaharian and 21
      intrapaleartic species were examined during spring (n = 176) and autumn (n =
      146), and were tested using a generic nested-PCR. RESULTS: All samples tested
      negative for Flaviviruses. The possible causes of unapparent shedding, along with
      ecological and epidemiological implications are discussed. CONCLUSIONS: The lack
      of detection of active virus shedding in these bird species does not exclude the
      circulation of these viruses within the Trentino-Alto Adige region, as reported
      in previous studies. The possible ecological implications are discussed.

PMID- 24119321
TI  - Unloading reaction during sudden ankle inversion in healthy adults.
AB  - The purpose of this research study was to determine the dynamics of early human
      response from sudden ankle inversion (30 degrees  tilt). Changes in vertical
      ground reaction forces (GRFs) following trapdoor release in a group of healthy
      subjects were compared to those from the similar experiments using a chair with
      two U shaped steel legs and matched weights of the human subjects. The
      experiments with the chair were further repeated with additional foam paddings at
      their bases to introduce visco-elastic properties to legs of the chair. Following
      the trapdoor release a decrease in the vertical ground reaction force under the
      inverting leg and subsequent increase in the supporting leg were observed in both
      human and chair experiments. The short onset of changes in vertical GRFs in our
      experiments indicate that the dynamic features of early response following
      trapdoor release are primarily due to mechanical events and may not be
      significantly affected by the neuromuscular reaction of human subjects. 

PMID- 24119322
TI  - The RootScope: a simple high-throughput screening system for quantitating gene
      expression dynamics in plant roots.
AB  - BACKGROUND: High temperature stress responses are vital for plant survival. The
      mechanisms that plants use to sense high temperatures are only partially
      understood and involve multiple sensing and signaling pathways. Here we describe
      the development of the RootScope, an automated microscopy system for quantitating
      heat shock responses in plant roots. RESULTS: The promoter of Hsp17.6 was used to
      build a Hsp17.6p:GFP transcriptional reporter that is induced by heat shock in
      Arabidopsis. An automated fluorescence microscopy system which enables multiple
      roots to be imaged in rapid succession was used to quantitate Hsp17.6p:GFP
      response dynamics. Hsp17.6p:GFP signal increased with temperature increases from
      28 degrees C to 37 degrees C. At 40 degrees C the kinetics and localization of
      the response are markedly different from those at 37 degrees C. This suggests
      that different mechanisms mediate heat shock responses above and below 37 degrees
      C. Finally, we demonstrate that Hsp17.6p:GFP expression exhibits wave like
      dynamics in growing roots. CONCLUSIONS: The RootScope system is a simple and
      powerful platform for investigating the heat shock response in plants.

PMID- 24119323
TI  - Zinc monotherapy and a low-copper diet are beneficial in patients with Wilson
      disease after liver transplantation.

PMID- 24119324
TI  - Acceptability of oral and topical HIV chemoprophylaxis in India: implications for
      at-risk women and men who have sex with men.
AB  - With reducing HIV prevalence, India has made gains in containing the epidemic.
      Yet, unprotected sex and commercial sex work, unprotected anal sex between men
      and needle sharing among intravenous drug users continue to drive the epidemic.
      Development of effective, safe and acceptable topical (microbicides) and oral
      (pre-exposure prophylaxis (PrEP)) chemoprophylaxis could augment the already
      available tools for HIV prevention. This paper reviews the acceptability of
      topical microbicides and oral PrEP, in the context of the nature of the HIV
      epidemic, the sociocultural norms and the acceptability data obtained from
      studies carried out in India. Overall, men and women have a positive attitude
      towards the concept and use of microbicide products. Self-perceptions of HIV
      risk, product attributes, ease and convenience of use during sex, gender norms,
      the sociocultural context and the potential for undisclosed use were important
      factors influencing acceptability. A multipurpose product that would
      simultaneously address women's contraceptive and disease prevention needs would
      be devoid of the stigma attached to an anti-HIV product and may be more
      acceptable. Limited information on the acceptability of oral PrEP amongst high
      risk groups merits further research, including carrying out demonstration
      projects for program introduction. 

PMID- 24119325
TI  - [Multiple system atrophy: hot cross bun and Santiaguino sign].

PMID- 24119327
TI  - Are hospitalized patients aware of the risks and consequences of central line
      associated bloodstream infections?
AB  - We surveyed patients to determine awareness and knowledge regarding risks and
      consequences of a central line and found that most patients were aware of the
      signs and symptoms and the negative outcomes of central line-associated
      bloodstream infections (CLABSI). Forty percent thought that education regarding
      CLABSI could be improved, 22% could not recall discussing risks of infection of a
      central line with a health care worker, and only 46% of patients recalled
      receiving an informational flyer in the hospital regarding CLABSI. Our results
      suggest that efforts to involve and engage patients in interventions for CLABSI
      prevention are likely to be of benefit.

PMID- 24119328
TI  - Clinical efficacy of composite versus ceramic inlays and onlays: a systematic
      review.
AB  - OBJECTIVES: Large tooth substance losses are frequent in posterior teeth because
      of primary caries or aging restorations. Inlays and onlays are often the minimal
      invasive solution in such cases, but the efficacy of the composite and ceramic
      materials used is unknown. We performed a systematic review of randomized
      controlled trials comparing the efficacy of composite and ceramic inlays or
      onlays. DATA SOURCES: MEDLINE, Embase and the Cochrane Central Register of
      Controlled Trials were searched without any restriction on date or language, as
      were references of eligible studies and ClinicalTrials.gov. STUDY SELECTION:
      Eligible studies were randomized trials comparing the clinical efficacy of
      composite to ceramic inlays or onlays in adults with any clinical outcome for at
      least 6 months. From 172 records identified, we examined reports of 2 randomized
      controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and
      exhibiting a high-risk of bias. Outcomes were clinical scores and major failures.
      The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic
      inlays although not statistically significant. The reported clinical scores
      (United States Public Health Services and Californian Dental Association) showed
      considerable heterogeneity between trials and could not be combined. CONCLUSIONS:
      We have very limited evidence that ceramics perform better than composite
      material for inlays in the short term. However, this result may not be valid in
      the long term, and other trials are needed. Trials should follow Federation
      dentaire internationale recommendations and enhance their methodology. Trials
      comparing composite and ceramic onlays are needed.

PMID- 24119330
TI  - Early signs of brain asymmetry.
AB  - A new study shows a leftward asymmetry of the choroid plexus in two-thirds of
      first-trimester human fetuses. This is the earliest brain asymmetry so far
      identified and may be a precursor to other asymmetries, including that of the
      temporal planum, which is evident from the 31st week of gestation. 

PMID- 24119329
TI  - Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan.
AB  - BACKGROUND: An evidence-based strategy exists to reduce maternal morbidity and
      mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be
      difficult to implement in low-resource settings. This study examines whether
      facilities that provide emergency obstetric and newborn care (EmONC) in
      Afghanistan have the capacity to manage severe PE/E cases. METHODS: A further
      analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment.
      Assessors observed equipment and supplies available, and services provided at 78
      of the 127 facilities offering comprehensive EmONC services and interviewed 224
      providers. The providers also completed a written case scenario on severe PE/E.
      Descriptive statistics were used to summarize facility and provider
      characteristics. Student t-test, one-way ANOVA, and chi-square tests were
      performed to determine whether there were significant differences between
      facility types, doctors and midwives, and trained and untrained providers.
      RESULTS: The median number of severe PE/E cases in the past year was just 5
      (range 0-42) at comprehensive health centers (CHCs) and district hospitals,
      compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at
      regional and specialized hospitals (p < 0.001). Most facilities had the drugs and
      supplies needed to treat severe PE/E, including the preferred anticonvulsant,
      magnesium sulfate (MgSO4). One-third of the smallest facilities and half of
      larger facilities reported administering a second-line drug, diazepam, in some
      cases. In the case scenario, 96% of doctors and 89% of midwives recognized that
      MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of
      midwives also thought diazepam had a role to play. Providers who were trained on
      the use of MgSO4 scored significantly higher than untrained providers on six of
      20 items in the case scenario. Providers at larger facilities significantly
      outscored those at smaller facilities on five items. There was a significant
      difference between doctors and midwives on only one item: continued use of anti
      hypertensives after convulsions are controlled. CONCLUSIONS: Drugs and supplies
      needed to treat severe PE/E are widely available at EmONC facilities in
      Afghanistan, but providers lack knowledge in some areas, especially concerning
      the use of MgSO4 and diazepam. Providers who have specialized training or work at
      larger facilities are better at managing cases of severe PE/E. The findings
      suggest a need to clarify service delivery guidelines, offer refresher training,
      and reinforce best practices with supervision and reinforcement.

PMID- 24119331
TI  - Ulcerative colitis, Crohn's disease and irritable bowel syndrome patients need
      fecal transplant research and treatment.

PMID- 24119332
TI  - Health care experiences of U.S. retirees living in Mexico and Panama: a
      qualitative study.
AB  - BACKGROUND: Retirement migration from northern countries to southern countries is
      increasing in both Europe and North America, and retiree experiences will impact
      future migration and health services utilization. We therefore sought to describe
      the healthcare experiences and perceptions of retired U.S. citizens currently
      living in Mexico and Panama. METHODS: 46 retired U.S. citizens (23 per country)
      who had been hospitalized (61%) or had a chronic health condition (78%) in two
      regions per country with large communities of retired U.S. citizens were
      identified. Detailed semi-structured interviews were conducted to explore
      experiences with, attitudes toward, and costs of healthcare. Interviews were
      analyzed using quantitative and qualitative methods. RESULTS: Respondents
      averaged 68-70 years old, were well educated, had few physical dependencies, and
      had moderate incomes. They praised physician services as more personalized than
      in the U.S. and home care as inexpensive and widely available, expressed
      favorable opinions regarding outpatient and dental care, gave mixed ratings on
      hospital services, and expressed concerns about emergency services. Numerous
      concerns about health insurance were expressed, including the unavailability of
      Medicare and reductions in Tricare. Payment concerns and lack of data on local
      health providers made deciding where to obtain services challenging. CONCLUSIONS:
      Retirees living abroad report dilemmas regarding healthcare choices, insurance
      availability, and quality of care. As this population segment grows, pressure
      will increase for policy and business solutions to existing medical care
      challenges.

PMID- 24119333
TI  - The prognostic value of mechanical left ventricular dyssynchrony in patients with
      acute coronary syndrome.
AB  - BACKGROUND: Echocardiography is a well-established tool for risk stratification
      in patients with acute coronary syndrome (ACS). ACS has significant impact on LV
      dyssynchrony, and detrimental effects on systolic function and long term outcome.
      The aims of this study were to determine whether LV dyssynchrony carries any
      predictive information in an unselected ACS population and to evaluate if it has
      any incremental value to the information given from conventional
      echocardiographic measurements. METHODS: The study included 227 consecutive ACS
      patients. Primary endpoint was the composite of death, new MI, or
      rehospitalisation due to heart failure. Dyssynchrony was measured as
      intersegmental variation of time to peak strain, the post systolic index (PSI)
      and myocardial performance index (MPI) with the standard deviation and difference
      between lowest and highest value (delta) expressing the amount of dyssynchrony.
      Septal-lateral delay was also tested. All dyssynchrony parameters were compared
      with Ejection fraction (EF). RESULTS: The median follow up time was 53 months. 85
      patients reached the combined endpoint. Patients with and without a subsequent
      combined endpoint differed significantly regarding calculated SD: s and delta
      value for PSI, time to peak 2D-strain and MPI but not regarding septal-lateral
      delay. In ROC-analysis none of the dyssynchrony parameters had larger AUC than
      EF. When adjusting for traditional risk factors none of the dyssynchrony
      parameters remained associated with outcome, whereas EF still did. CONCLUSION: LV
      dyssynchrony seem to have significant prognostic information in patient with
      acute coronary syndrome but in comparison to conventional parameters such as EF
      there is no incremental value of this information.

PMID- 24119334
TI  - The accuracy of prostate volume measurement from ultrasound images: a quasi-Monte
      Carlo simulation study using magnetic resonance imaging.
AB  - Prostate volume is an important parameter to guide management of patients with
      benign prostatic hyperplasia (BPH) and to deliver clinical trial endpoints.
      Generally, simple 2D ultrasound (US) approaches are favoured despite the
      potential for greater accuracy afforded by magnetic resonance imaging (MRI) or
      complex US procedures. In this study, different approaches to estimate prostate
      size are evaluated with a simulation to select multiple organ cross-sections and
      diameters from 22 MRI-defined prostate shapes. A quasi-Monte Carlo (qMC) approach
      is used to simulate multiple probe positions and angles within prescribed limits
      resulting in a range of dimensions. The basic ellipsoid calculation which uses
      two scanning planes compares well to the MRI volume across the range of prostate
      shapes and sizes (R=0.992). However, using an appropriate linear regression
      model, accurate volume estimates can be made using prostate diameters calculated
      from a single scanning plane. 

PMID- 24119335
TI  - Segmentation method of intravascular ultrasound images of human coronary
      arteries.
AB  - The goal of this study was to show the feasibility of a 2D segmentation fast
      marching method (FMM) in the context of intravascular ultrasound (IVUS) imaging
      of coronary arteries. The original FMM speed function combines gradient-based
      contour information and region information, that is the gray level probability
      density functions of the vessel structures, that takes into account the
      variability in appearance of the tissues and the lumen in IVUS images acquired at
      40 MHz. Experimental results on 38 in vivo IVUS sequences yielded mean point-to
      point distances between detected vessel wall boundaries and manual validation
      contours below 0.11 mm, and Hausdorff distances below 0.33 mm, as evaluated on
      3207 images. The proposed method proved to be robust in taking into account
      various artifacts in ultrasound images: partial shadowing due to calcium
      inclusions within the plaque, side branches adjacent to the main artery to
      segment, the presence of a stent, injection of contrast agent or dissection, as
      tested on 209 images presenting such artifacts.

PMID- 24119336
TI  - Consumption of lead-shot cervid meat and blood lead concentrations in a group of
      adult Norwegians.
AB  - Several recent investigations have reported high concentrations of lead in
      samples of minced cervid meat. This paper describes findings from a Norwegian
      study performed in 2012 among 147 adults with a wide range of cervid game
      consumption. The main aim was to assess whether high consumption of lead-shot
      cervid meat is associated with increased concentration of lead in blood. A second
      aim was to investigate to what extent factors apart from game consumption explain
      observed variability in blood lead levels. Median (5 and 95 percentile) blood
      concentration of lead was 16.6 ug/L (7.5 and 39 ug/L). An optimal multivariate
      linear regression model for log-transformed blood lead indicated that cervid game
      meat consumption once a month or more was associated with approximately 31%
      increase in blood lead concentrations. The increase seemed to be mostly
      associated with consumption of minced cervid meat, particularly purchased minced
      meat. However, many participants with high and long-lasting game meat intake had
      low blood lead concentrations. Cervid meat together with number of bullet shots
      per year, years with game consumption, self-assembly of bullets, wine consumption
      and smoking jointly accounted for approximately 25% of the variation in blood
      lead concentrations, while age and sex accounted for 27% of the variance. Blood
      lead concentrations increased approximately 18% per decade of age, and men had on
      average 30% higher blood lead concentrations than women. Hunters who assembled
      their own ammunition had 52% higher blood lead concentrations than persons not
      making ammunition. In conjunction with minced cervid meat, wine intake was
      significantly associated with increased blood lead. Our results indicate that
      hunting practices such as use of lead-based ammunition, self-assembling of lead
      containing bullets and inclusion of lead-contaminated meat for mincing to a large
      extent determine the exposure to lead from cervid game consumption.

PMID- 24119337
TI  - Outcome of lesionectomy in medically refractory epilepsy due to non-mesial
      temporal sclerosis (non-MTS) lesions.
AB  - OBJECTIVES: To analyze the seizure outcome of lesionectomy for refractory
      epilepsy secondary to non-mesial temporal sclerosis (non-MTS) lesions. METHODS:
      Sixty-eight patients with non-MTS lesions (M:F=42:26; age at onset: 11.7+/-9.6
      years; age at surgery: 21.1+/-9.4 years), who underwent lesionectomy for
      refractory epilepsy were analyzed. The age at onset, frequency/type of seizure,
      MRI findings, video-EEG, histopathology and Engel's grading at 1 year/last follow
      up were recorded. RESULTS: The duration of epilepsy at surgery was 9.9+/-6.9
      years. The location of lesions were: temporal: 41 (60.3%); frontal: 21 (30.9%);
      parietal: 6 (8.8%). The type of lesionectomies performed were temporal 41
      (60.3%), extra-temporal: 25 (36.8%), temporo-frontal and temporo-parietal: 1
      (1.5%) patient each. The histopathological diagnosis were neoplastic: 32 (47.1%),
      cortical dysplasia: 19 (27.9%), other focal lesions: 17 (25%). At mean follow up
      of 2.9+/-2.1 years (median: 2.6 years), outcome was - Engel's class I: 43
      (63.2%), IIa: 14 (20.6%), III: 7 (10.3%), IV: 4 (5.9%). Good seizure control
      (Engel's class I/IIa) was achieved in 57 (83.8%) patients. The good prognostic
      markers included temporal seizures, extended lesionectomy and AEDs after surgery
      while poor prognostic marker was gliotic lesion on histopathology. CONCLUSION:
      Following lesionectomy due to non-MTS lesions, seizure freedom (Engel I) was
      noted in about 63.2% of patients, which is comparable to other series and
      reiterates the effectiveness of lesionectomy for seizure control.

PMID- 24119338
TI  - A survey of U.S. obstetrician-gynecologists' clinical and epidemiological
      knowledge of cryptosporidiosis in pregnancy.
AB  - Although cryptosporidiosis is frequently diagnosed in the U.S., there has been
      very little assessment of obstetrician-gynaecologist knowledge about this
      disease. In 2010, we surveyed U.S. obstetricians about the diagnosis, treatment
      and epidemiology of cryptosporidiosis. Data were examined through univariable
      analysis and multivariable regression models. Of 1000 obstetrician-gynaecologists
      surveyed, 431 (43.1%) responded. Only 44.4% of respondents correctly identified
      that prolonged, intermittent diarrhoea would lead them to consider
      cryptosporidiosis in a differential diagnosis. Routine ova and parasites (O&P)
      testing was incorrectly chosen to identify Cryptosporidium in stool by 30.4% of
      respondents. Questions about nitazoxanide, the only drug approved by the U.S.
      Food & Drug Administration (FDA) for treatment of cryptosporidiosis, were the
      most frequently missed questions. Only 9.0% of respondents correctly classified
      nitazoxanide as an FDA pregnancy Category B drug, and only 5.6% of respondents
      correctly indicated that FDA approved nitazoxanide for immunocompetent patients
      aged >=1 years. Regarding prevention- and control-related knowledge, only 14.1%
      of respondents correctly indicated that alcohol-based hand sanitizers were not
      effective at inactivating Cryptosporidium spp., and <10% correctly indicated that
      cryptosporidiosis is a reportable disease in their state of practice.
      Multivariable analysis found that >=19 years in practice was positively
      associated with O&P diagnostic testing knowledge, while rural and urban non-inner
      city practice location, compared with suburban practice location, was positively
      associated with nitazoxanide knowledge. The low level of knowledge among
      obstetrician-gynaecologists about cryptosporidiosis indicates a need to develop
      resources for physicians about all aspects of cryptosporidiosis, particularly on
      diagnosis, treatment and prevention strategies.

PMID- 24119339
TI  - Qualitative exploration of HIV-related sexual behaviours and multiple
      partnerships among Chinese men who have sex with men living in a rural area of
      Yunnan Province, China.
AB  - BACKGROUND: The HIV epidemic has been spreading rapidly among men who have sex
      with men (MSM) in China. The present study explored the pattern of HIV-related
      high-risk sexual practices among MSM in a rural Chinese setting. METHODS: Data
      were collected by semistructured in-depth interviews conducted among 15 MSM in
      Yuxi Prefecture, Yunnan Province, China. Fifteen respondents were recruited
      through a local non-governmental organisation via purposive sampling. Thematic
      analysis was used. RESULTS: Technological changes, risk behaviours, social stigma
      and high migration rates have played a significant role in the spread of HIV
      among MSM in rural China. The Internet has become the primary channel for
      soliciting casual sex partners in the MSM community. Bisexuality and having
      concurrent and multiple sexual partners were common among rural MSM. A large
      number of sexual partners and low condom use in all MSM partnership types were
      noted. Due to Chinese cultural traditions and social stigma, Chinese rural MSM
      were reluctant to disclose their homosexuality. Rural-to-urban migrant MSM were
      often engaged in the commercial sex trade. CONCLUSIONS: Rural MSM is a
      distinctive and complex population with multiple identities in China. Concurrent
      multiple sexual partnerships, high mobility and low disclosure rate are the major
      challenges for HIV prevention and intervention programs in MSM.

PMID- 24119340
TI  - Correlated SEM, FIB-SEM, TEM, and NanoSIMS imaging of microbes from the hindgut
      of a lower termite: methods for in situ functional and ecological studies of
      uncultivable microbes.
AB  - The hindguts of lower termites harbor highly diverse, endemic communities of
      symbiotic protists, bacteria, and archaea essential to the termite's ability to
      digest wood. Despite over a century of experimental studies, ecological roles of
      many of these microbes are unknown, partly because almost none can be cultivated.
      Many of the protists associate with bacterial symbionts, but hypotheses for their
      respective roles in nutrient exchange are based on genomes of only two such
      bacteria. To show how the ecological roles of protists and nutrient transfer with
      symbiotic bacteria can be elucidated by direct imaging, we combined stable
      isotope labeling (13C-cellulose) of live termites with analysis of fixed hindgut
      microbes using correlated scanning electron microscopy, focused ion beam-scanning
      electron microscopy (FIB-SEM), transmission electron microscopy, and high
      resolution imaging mass spectrometry (NanoSIMS). We developed methods to prepare
      whole labeled cells on solid substrates, whole labeled cells milled with a FIB
      SEM instrument to reveal cell interiors, and ultramicrotome sections of labeled
      cells for NanoSIMS imaging of 13C enrichment in protists and associated bacteria.
      Our results show these methods have the potential to provide direct evidence for
      nutrient flow and suggest the oxymonad protist Oxymonas dimorpha phagocytoses and
      enzymatically degrades ingested wood fragments, and may transfer carbon derived
      from this to its surface bacterial symbionts. 

PMID- 24119341
TI  - Early onset muscle weakness and disruption of muscle proteins in mouse models of
      spinal muscular atrophy.
AB  - BACKGROUND: The childhood neuromuscular disease spinal muscular atrophy (SMA) is
      caused by mutations or deletions of the survival motor neuron (SMN1) gene.
      Although SMA has traditionally been considered a motor neuron disease, the muscle
      specific requirement for SMN has never been fully defined. Therefore, the purpose
      of this study was to investigate muscle defects in mouse models of SMA. METHODS:
      We have taken advantage of two different mouse models of SMA, the severe Smn-/
      ;SMN2 mice and the less severe Smn2B/- mice. We have measured the maximal force
      produced from control muscles and those of SMA model mice by direct stimulation
      using an ex vivo apparatus. Immunofluorescence and immunoblot experiments were
      performed to uncover muscle defects in mouse models of SMA. Means from control
      and SMA model mice samples were compared using an analysis of variance test and
      Student's t tests. RESULTS: We report that tibialis anterior (TA) muscles of
      phenotype stage Smn-/-;SMN2 mice generate 39% less maximal force than muscles
      from control mice, independently of aberrant motor neuron signal transmission. In
      addition, during muscle fatigue, the Smn-/-;SMN2 muscle shows early onset and
      increased unstimulated force compared with controls. Moreover, we demonstrate a
      significant decrease in force production in muscles from pre-symptomatic Smn-/
      ;SMN2 and Smn2B/- mice, indicating that muscle weakness is an early event
      occurring prior to any overt motor neuron loss and muscle denervation. Muscle
      weakness in mouse models of SMA was associated with a delay in the transition
      from neonatal to adult isoforms of proteins important for proper muscle
      contractions, such as ryanodine receptors and sodium channels. Immunoblot
      analyses of extracts from hindlimb skeletal muscle revealed aberrant levels of
      the sarcoplasmic reticulum Ca2+ ATPase. CONCLUSIONS: The findings from this study
      reveal a delay in the appearance of mature isoforms of proteins important for
      muscle contractions, as well as muscle weakness early in the disease etiology,
      thus highlighting the contributions of skeletal muscle defects to the SMA
      phenotype.

PMID- 24119342
TI  - Valproate induced hyperammonemic encephalopathy successfully treated with
      levocarnitine.
AB  - Valproate-induced hyperammonemic encephalopathy is an unusual but serious adverse
      effect that is usually characterized by the acute onset of impaired
      consciousness, focal neurological symptoms and increased seizure frequency. It
      has been reported to occur at therapeutic valproate levels. We report a patient
      who developed valproate-induced hyperammonemic encephalopathy after a short
      treatment with valproate and was successfully treated with levocarnitine. We
      discuss this patient and review the literature regarding the use of levocarnitine
      in similar patients. 

PMID- 24119343
TI  - Evaluating RadLex and real world radiology reporting: are we there yet?

PMID- 24119344
TI  - Evaluating the completeness of RadLex in the chest radiography domain.
AB  - RATIONALE AND OBJECTIVES: RadLex was developed to create a unified language for
      radiologists. Despite the large number of terms, little research has evaluated
      the degree to which RadLex contains terms frequently used in clinical practice.
      The purposes of this project are to estimate the completeness of RadLex in the
      chest radiography domain and to characterize the absent terms. We chose chest
      radiography because it is a common exam generating a large number of reports, and
      the terms used represent a relatively well-circumscribed set of terms compared to
      other anatomic regions and modalities. MATERIALS AND METHODS: We collected a
      random sample of 100 chest radiograph reports from 1 month of routine clinical
      practice of three board-certified radiologists. We parsed each report's findings
      and impression sections into individual objects. An "object" was defined as any
      discrete physical object, body part, observation, descriptive modifier,
      diagnosis, or procedure. Objects were compared to RadLex by entering the object
      into the RadLex Term Browser. We calculated descriptive statistics and compared
      the match rate across RadLex categories. RESULTS: We identified 339 unique
      objects, with an overall match rate of 62%. The match rate for each category was
      anatomic object, 77%; physiological condition, 73%; physical object, 65%; imaging
      observation, 47%; procedure, 0%; other, 41% (P < .0005). CONCLUSIONS: Our study
      shows that despite the large number of terms in RadLex, terms are still absent
      and complexities in the definitions of terms exist. However, increasing the
      completeness and refining the definitions in RadLex is easily surmountable,
      possibly using manual methods.

PMID- 24119345
TI  - Scatter correction associated with dedicated dual-source CT hardware improves
      accuracy of lung air measures.
AB  - RATIONALE AND OBJECTIVES: Accurate assessment of air density used to
      quantitatively characterize amount and distribution of emphysema in chronic
      obstructive pulmonary disease (COPD) subjects has remained challenging.
      Hounsfield units (HU) within tracheal air can be considerably less negative than 
      1000 HU. This study has sought to characterize the effects of improved scatter
      correction used in dual-source pulmonary computed tomography (CT). MATERIALS AND
      METHODS: Dual-source dual-energy (DSDE) and single-source (SS) scans taken at
      multiple energy levels and scan settings were acquired for quantitative
      comparison using anesthetized ovine (n = 6), swine (n = 13), and a lung phantom.
      Data were evaluated for the lung, inferior vena cava, and tracheal segments. To
      minimize the effect of cross-scatter, the phantom scans in the DSDE mode were
      obtained by reducing the current of one of the tubes to near zero. RESULTS: A
      significant shift in mean HU values in the tracheal regions of animals and the
      phantom is observed, with values consistently closer to -1000 HU in DSDE mode. HU
      values associated with SS mode demonstrated a positive shift of up to 32 HU. In
      vivo tracheal air measurements demonstrated considerable variability with SS
      scanning, whereas these values were more consistent with DSDE imaging. Scatter
      effects in the lung parenchyma differed from adjacent tracheal measures.
      CONCLUSION: Data suggest that the scatter correction introduced into the dual
      energy mode of imaging has served to provide more accurate CT lung density
      measures sought to quantitatively assess the presence and distribution of
      emphysema in COPD subjects. Data further suggest that CT images, acquired without
      adequate scatter correction, cannot be corrected by linear algorithms given the
      variability in tracheal air HU values and the independent scatter effects on lung
      parenchyma.

PMID- 24119346
TI  - Pulmonary functional imaging using hyperpolarized noble gas MRI: six years of
      start-up experience at a single site.
AB  - RATIONALE AND OBJECTIVES: In this review, we summarize our experience evaluating
      pulmonary function in 330 different subjects using hyperpolarized noble gas
      magnetic resonance imaging (MRI) after enrollment and screening of >1100 subjects
      with and without respiratory disease during the period February 1, 2006, through
      November 1, 2012. MATERIALS AND METHODS: We discuss the feasibility of
      hyperpolarized gas MRI research in a small nonhospital research unit and provide
      an overview of our experience since we initiated patient-based studies. We also
      discuss the importance of infrastructure support, collaboration, research
      trainees, and a large and willing patient population that helped to advance the
      research and technological deliverables. A summary of patient safety and
      tolerability, key feasibility, and research milestones is provided, as well as a
      roadmap for future studies. RESULTS: Hyperpolarized (3)He and (129)Xe gas MRI is
      feasible at smaller centers without significant human resources for large and
      small longitudinal studies by virtue of its excellent patient safety and
      tolerability, the speed with which images can be acquired and quantitatively
      analyzed and the high spatial-temporal dynamics of the method that allows for
      acute and chronic therapy studies. CONCLUSIONS: The hyperpolarized noble gas MRI
      community's highly collaborative efforts and motivation to further the
      development and application of this tool has resulted in a moment-of-opportunity
      to translate the method clinically to provide an improved understanding of
      pulmonary disease. There are, as well, new and unprecedented opportunities for
      the evaluation of disease progression and to help develop the new treatments and
      interventions critically required for chronic pulmonary disease.

PMID- 24119347
TI  - Comparison of chest dual-energy subtraction digital tomosynthesis and dual-energy
      subtraction radiography for detection of pulmonary nodules: initial evaluations
      in human clinical cases.
AB  - RATIONALE AND OBJECTIVES: To compare initial evaluations of chest dual-energy
      subtraction digital tomosynthesis (DES-DT) and dual-energy subtraction
      radiography (DES-R) for detection of pulmonary nodules. MATERIALS AND METHODS:
      DES-DT and DES-R systems with pulsed x-rays and rapid kV switching were used to
      evaluate pulmonary nodules (>4-6 mm, 2 nodules; >6-8 mm, 2 nodules; >8 mm, 32
      nodules). Multidetector computed tomography was used as a reference. A filtered
      back-projection algorithm was used to reconstruct low-voltage (60 kVp), high
      voltage (120 kVp), and soft-tissue or bone-subtracted tomograms of the desired
      layer thicknesses from the image data acquired during a single tomographic scan.
      DES-R images were processed from the low- and high-voltage images. To detect the
      pulmonary nodules, we used both systems to examine 36 patients with and 36
      patients without pulmonary nodules. Two radiologists and three doctors of
      pulmonary medicine (average experience, 18 years) performed receiver operating
      characteristic (ROC) curve analysis to evaluate the results. RESULTS: The ROC
      analysis results suggested that the detection ability was significantly better
      for DES-DT than for DES-R (P < .0001; 95% confidence interval: DES-DT, 0.94 [0.83
      0.99]; DES-R, 0.76 [0.68-0.85]; sensitivity: DES-DT, 87.7 +/- 2.9%; DES-R, 53.8
      +/- 3.5%; specificity: DES-DT, 78.3 +/- 5.6%; DES-R, 78.4 +/- 3.4%; accuracy: DES
      DT, 83.1 +/- 3.8%, DES-R, 66.1 +/- 2.0%). When the nodules were no longer
      superimposed over the normal structures, their characteristics and distribution
      could be observed much more clearly. CONCLUSION: Compared with DES-R, DES-DT
      provided greater sensitivity for detection of pulmonary nodules, particularly for
      the larger ones.

PMID- 24119348
TI  - Minimum detectable change in lung nodule volume in a phantom CT study.
AB  - RATIONALE AND OBJECTIVES: The change in volume of lung nodules is being examined
      as a measure of response to treatment. The aim of this study was to determine the
      minimum detectable change in nodule volume with the use of computed tomography.
      MATERIALS AND METHODS: Four different layouts of synthetic nodules with different
      shapes but with the same size (5, 8, 9, or 10 mm) for each layout were placed
      within an anthropomorphic phantom and scanned with a 16-detector-row computed
      tomography scanner using multiple imaging parameters. Nodule volume estimates
      were determined using a previously developed matched-filter estimator. Analysis
      of volume change was then conducted as a detection problem. For each nodule size,
      the pooled distribution of volume estimates was shifted by a percentage c to
      simulate a changing nodule, while accounting for standard deviation. The value of
      c resulting in a prespecified area under the receiver operating characteristic
      curve (AUC) was deemed the minimum detectable change for that AUC value. RESULTS:
      Both nodule size at baseline and choice of slice collimation protocol had an
      effect on the value of minimum detectable growth. For AUC = 0.95, the minimum
      detectable nodule growth in volume when using the thin-slice collimation protocol
      (16 * 0.75 mm) was 17%, 19%, and 15% for nodule sizes of 5, 8, and 9 mm,
      respectively. CONCLUSIONS: Our results indicate that an approximate bound for
      detectable nodule growth in subcentimeter nodules may be relatively small, on the
      order of 20% or less in volume for a thin-slice CT acquisition protocol.

PMID- 24119349
TI  - Comparative analysis of data collection methods for individualized modeling of
      radiologists' visual similarity judgments in mammograms.
AB  - RATIONALE AND OBJECTIVES: We conducted an observer study to investigate how the
      data collection method affects the efficacy of modeling individual radiologists'
      judgments regarding the perceptual similarity of breast masses on mammograms.
      MATERIALS AND METHODS: Six observers of varying experience levels in breast
      imaging were recruited to assess the perceptual similarity of mammographic
      masses. The observers' subjective judgments were collected using (i) a rating
      method, (ii) a preference method, and (iii) a hybrid method combining rating and
      ranking. Personalized user models were developed with the collected data to
      predict observers' opinions. The relative efficacy of each data collection method
      was assessed based on the classification accuracy of the resulting user models.
      RESULTS: The average accuracy of the user models derived from data collected with
      the hybrid method was 55.5 +/- 1.5%. The models were significantly more accurate
      (P < .0005) than those derived from the rating (45.3 +/- 3.5%) and the preference
      (40.8 +/- 5%) methods. On average, the rating data collection method was
      significantly faster than the other two methods (P < .0001). No time advantage
      was observed between the preference and the hybrid methods. CONCLUSIONS: A hybrid
      method combining rating and ranking is an intuitive and efficient way for
      collecting subjective similarity judgments to model human perceptual opinions
      with a higher accuracy than other, more commonly used data collection methods.

PMID- 24119350
TI  - Evaluation of the effect of computer-aided classification of benign and malignant
      lesions on reader performance in automated three-dimensional breast ultrasound.
AB  - RATIONALE AND OBJECTIVES: To investigate the effect of a newly developed computer
      aided diagnosis (CAD) system on reader interpretation of breast lesions in
      automated three-dimensional (3D) breast ultrasound. MATERIALS AND METHODS: A CAD
      system was developed to differentiate malignant lesions from benign lesions
      including automated lesion segmentation in three dimensions; extraction of lesion
      features such as spiculation, margin contrast, and posterior acoustic behavior;
      and a classification stage. Eighty-eight patients with breast lesions were
      included for an observer study: 47 lesions were malignant and 41 were benign.
      Eleven readers (seven radiologists and four residents) read the cases with and
      without CAD. We compared the performance of readers with and without CAD using
      receiver operating characteristic (ROC) analysis. RESULTS: The CAD system had an
      area under the ROC curve (AUC) of 0.92 for discriminating benign and malignant
      lesions, whereas the unaided reader AUC ranged from 0.77 to 0.92. Mean
      performance of inexperienced readers improved when CAD was used (AUC = 0.85
      versus 0.90; P = .007), whereas mean performance of experienced readers did not
      change with CAD (AUC = 0.89). CONCLUSIONS: By using the CAD system for
      classification of lesions in automated 3D breast ultrasound, which on its own
      performed as good as the best readers, the performance of inexperienced readers
      improved while that of experienced readers remained unaffected.

PMID- 24119351
TI  - Feasibility and acceptability of conducting a randomized clinical trial designed
      to improve interpretation of screening mammography.
AB  - PURPOSE: To describe recruitment, enrollment, and participation in a study of US
      radiologists invited to participate in a randomized controlled trial of two
      continuing medical education (CME) interventions designed to improve
      interpretation of screening mammography. METHODS: We collected recruitment,
      consent, and intervention-completion information as part of a large study
      involving radiologists in California, Oregon, Washington, New Mexico, New
      Hampshire, North Carolina, and Vermont. Consenting radiologists were randomized
      to receive either a 1-day live, expert-led educational session; to receive a self
      paced DVD with similar content; or to a control group (delayed intervention). The
      impact of the interventions was assessed using a preintervention-postintervention
      test set design. All activities were institutional review board approved and
      HIPAA compliant. RESULTS: Of 403 eligible radiologists, 151 of 403 (37.5%)
      consented to participate in the trial and 119 of 151 (78.8%) completed the
      preintervention test set, leaving 119 available for randomization to one of the
      two intervention groups or to controls. Female radiologists were more likely than
      male radiologists to consent to and complete the study (P = .03). Consenting
      radiologists who completed all study activities were more likely to have been
      interpreting mammography for 10 years or less compared to radiologists who
      consented and did not complete all study activities or did not consent at all.
      The live intervention group was more likely to report their intent to change
      their clinical practice as a result of the intervention compared to those who
      received the DVD (50% versus 17.6%, P = .02). The majority of participants in
      both interventions groups felt the interventions were a useful way to receive CME
      mammography credits. CONCLUSIONS: Community radiologists found interactive
      interventions designed to improve interpretative mammography performance
      acceptable and useful for clinical practice. This suggests CME credits for
      radiologists should, in part, be for examining practice skills.

PMID- 24119352
TI  - Accuracy of axillary lymph node staging in breast cancer patients: an observer
      performance study comparison of MRI and ultrasound.
AB  - PURPOSE: To compare magnetic resonance imaging (MRI) and ultrasound (US) for
      axillary lymph node (LN) staging in breast cancer patients in an observer
      performance study. MATERIALS AND METHODS: An observer-performance study was
      conducted with five breast radiologists reviewing 50 consecutive patients of
      newly diagnosed invasive breast cancer with the use of ipsilateral axillary MRI
      and US. LN status was pathologically proved in all patients. Each observer
      reviewed the images in two separate sessions: one for MRI and the other for US.
      Observers were asked to indicate their confidence of the presence of at least one
      ipsilateral metastatic LN on a quasi-continuous rating scale and whether they
      recommend percutaneous biopsy preoperatively. Receiver operating characteristic
      (ROC) analysis and area under the ROC curve were used to characterize diagnostic
      performance. Sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) were calculated from whether observers
      recommended biopsy. RESULTS: There were no statistically significant differences
      in each observer's performance between MRI and US, or in the performance of all
      observers as a group, in terms of ROC analysis. There were no statistically
      significant differences in sensitivity, specificity, PPV, or NPV between MRI and
      US, but there were statistically significant improvements in specificity and PPV
      from either MRI or US alone to MRI and US combined. CONCLUSIONS: Observer
      performance on MRI and US are comparable for axillary LN staging. When US and MRI
      are concordant for positive findings, higher specificity and PPV can be obtained.

PMID- 24119353
TI  - Dose-modified 256-MDCT of the abdomen using low tube current and hybrid iterative
      reconstruction.
AB  - RATIONALE AND OBJECTIVES: To evaluate the performance of hybrid iterative
      reconstruction technique (h-IRT) on image quality (IQ) in abdominal dose-modified
      (DM) scans in phantom and in patients in comparison to filtered back projection
      (FBP). MATERIALS AND METHODS: An anthropomorphic phantom was scanned using
      various kVp (80-140) and mAs (25-100) settings. Images were reconstructed with
      FBP and h-IRT levels (1-6). In 69 adults (59.6 +/- 13.54 years; 20 male, 49
      female), DM computed tomography (CT) scans were performed using 120 kVp and 100
      120 mAs. In 25/69, 5-mm FBP and h-IRT (levels 1-4 and 5) images were analyzed to
      validate IQ. The subsequent 44/69 had FBP and h-IRT (level 4) images
      reconstructed. Two readers evaluated 188 image series for IQ, noise, and
      artifacts. Objective and subjective data were analyzed using t-test and Wilcoxon
      signed-rank test, respectively. In 46/69 patients, prior dose CT was available
      for dose comparison. RESULTS: In the phantom, noise reduction ranged from 12% (h
      IRT level 1) to 50% (level 6). In patients, h-IRT level 4 images were rated
      diagnostic in 69/69 exams but DM-FBP images were found nondiagnostic in 20/69
      patients. The size-specific dose estimate (SSDE) was reduced by 55% in the dose
      modified CT group, (SSDE:4.55 +/- 1.15 mGy) over the prior dose protocol
      (SSDE:10.21 +/- 3.5 mGy, P < .0001). CONCLUSION: h-IRT improved IQ in abdominal
      DM-CT scans in phantom and in patients. Dose improvements were greater in smaller
      patients than larger ones.

PMID- 24119354
TI  - Computer-aided assessment of regional abdominal fat with food residue removal in
      CT.
AB  - RATIONALE AND OBJECTIVES: Separate quantification of abdominal subcutaneous and
      visceral fat regions is essential to understand the role of regional adiposity as
      risk factor in epidemiological studies. Fat quantification is often based on
      computed tomography (CT) because fat density is distinct from other tissue
      densities in the abdomen. However, the presence of intestinal food residues with
      densities similar to fat may reduce fat quantification accuracy. We introduce an
      abdominal fat quantification method in CT with interest in food residue removal.
      MATERIALS AND METHODS: Total fat was identified in the feature space of
      Hounsfield units and divided into subcutaneous and visceral components using
      model-based segmentation. Regions of food residues were identified and removed
      from visceral fat using a machine learning method integrating intensity, texture,
      and spatial information. Cost-weighting and bagging techniques were investigated
      to address class imbalance. RESULTS: We validated our automated food residue
      removal technique against semimanual quantifications. Our feature selection
      experiments indicated that joint intensity and texture features produce the
      highest classification accuracy at 95%. We explored generalization capability
      using k-fold cross-validation and receiver operating characteristic (ROC)
      analysis with variable k. Losses in accuracy and area under ROC curve between
      maximum and minimum k were limited to 0.1% and 0.3%. We validated tissue
      segmentation against reference semimanual delineations. The Dice similarity
      scores were as high as 93.1 for subcutaneous fat and 85.6 for visceral fat.
      CONCLUSIONS: Computer-aided regional abdominal fat quantification is a reliable
      computational tool for large-scale epidemiological studies. Our proposed
      intestinal food residue reduction scheme is an original contribution of this
      work. Validation experiments indicate very good accuracy and generalization
      capability.

PMID- 24119355
TI  - Distribution of abdominal aortic calcium by computed tomography: impact of
      analysis method on quantitative calcium score.
AB  - RATIONALE AND OBJECTIVES: Abdominal aortic calcification (AAC) can be quantified
      using computed tomography (CT), but imaging planes are prescribed based on bony
      landmarks, so that individual variation between the landmark and the aortoiliac
      junction can result in variable aortic coverage. In the Framingham CT substudy,
      we scanned a 15-cm (Z-direction) abdominal segment cranial to the S1 vertebral
      body. We sought to determine the range and distribution of length of aorta
      scanned and the distribution of AAC within the abdominal aorta and to compare
      burden of AAC measured from fixed-length segments versus AAC from all slices
      cranial to the aortoiliac bifurcation. MATERIALS AND METHODS: AAC was quantified
      by modified Agatston score (AS) in 100 Framingham Heart Study participants (60 +/
      13 years old, 51 men). We compared the AS measured from 5-cm and 8-cm segments
      with the ASALL (total visualized aorta). RESULTS: Of 100, 73 participants had AAC
      >0. The total length of aorta imaged was >=8 cm in 84% of participants.
      Qualitatively, 5-cm and 8-cm segments correctly identified 96% and 99%,
      respectively, of participants as having or not having AAC. Quantitatively, AS8cm
      was within 20% of ASALL in four-fifths and within 30% of ASALL in nine-tenths of
      participants. AS5cm more severely underestimated ASALL. CONCLUSION: The use of S1
      as the caudal imaging landmark in a 15-cm slab yields >=8 cm aortic coverage in
      most adults. Both 5-cm and 8-cm analysis strategies are comparable to analyzing
      the total visualized abdominal aorta for prevalent AAC, but only 8-cm segment
      analysis yields quantitatively similar measures of AAC.

PMID- 24119356
TI  - Iterative reconstructions versus filtered back-projection for urinary stone
      detection in low-dose CT.
AB  - RATIONALE AND OBJECTIVES: To evaluate prospectively, in patients with suspected
      or known urinary stone disease, the image quality and diagnostic confidence of
      nonenhanced abdominal low-dose computed tomography (CT) with iterative
      reconstruction (IR) compared to filtered back-projection (FBP). MATERIALS AND
      METHODS: Fifty consecutive patients with suspected (n = 33) or known (n = 17)
      urinary stone disease underwent nonenhanced abdominal low-dose CT (120 kVp, 30
      effective mAs, 1.6 +/- 0.5 mSv). Reconstructions were performed with sinogram
      affirmed IR and with FBP. Attenuation (in Hounsfield units) was measured in
      subcutaneous fat and urinary bladder; image noise was determined. Two readers
      assessed image quality, number and location of urinary calculi were recorded, and
      diagnostic confidence was assessed. Statistical analyses included Mann-Whitney,
      Friedman's two-way, Wilcoxon signed rank, Pearson's, and Spearman's rank order
      correction tests. RESULTS: Attenuation of urinary bladder (P = .208, reader 1; P
      = .123, reader 2) and fat (P = .568, reader 1; P = .834, reader 2) was similar
      among FBP and IR datasets. Image noise was reduced in IR datasets by 40.1% (P <
      .001). IR improved image quality (P < .01), and obesity as factor impairing image
      quality was noted in FBP but not in IR images (P < .05). There was no significant
      difference in number of calculi in datasets reconstructed with IR and FBP (P =
      .102, reader 1; P = .059, reader 2). Diagnostic confidence regarding
      identification of urinary calculi improved with IR (P < .05, reader 1; P < .01,
      reader 2). CONCLUSION: IR improves image quality and confidence for diagnosing
      urinary stone disease in abdominal low-dose CT.

PMID- 24119357
TI  - MRI-diagnosed nonalcoholic fatty liver disease is correlated to insulin
      resistance in adolescents.
AB  - RATIONALE AND OBJECTIVES: To evaluate the presence of nonalcoholic fatty liver
      disease (NAFLD) in eutrophic and obese adolescents with magnetic resonance
      imaging (MRI) and its relationship to insulin resistance and other potential
      biomarkers. MATERIALS AND METHODS: A total of 50 adolescents (aged 11-17 years),
      including 24 obese and 26 eutrophic adolescents, were evaluated using MRI exams
      for NAFLD diagnosis. Blood analysis was performed to measure glucose, insulin,
      total cholesterol, high-density lipoprotein cholesterol, triglycerides,
      fibrinogen, aminotransferases, alkaline phosphatase, gamma-gt, and C-reactive
      protein. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index
      was also calculated. Laboratory test results and anthropometric assessment were
      statistically analyzed to determine potential correlation with NAFLD prevalence.
      RESULTS: The prevalence of NAFLD among the obese was significantly higher (83.3%;
      CI 95: 64.5-94.5%) than that of the eutrophic group (19.2%; CI 95: 7.4-37.6%). In
      multivariate analysis, only HOMA-IR was an independent risk factor for diagnosis
      NAFLD using MRI. Compared to eutrophic adolescents, the obese adolescents had
      significantly higher levels for all parameters measured except for total and high
      density lipoprotein cholesterol, which were significantly lower. CONCLUSION: The
      prevalence of NAFLD was 19.2% among eutrophic patients and 83.3% among obese
      patients. Only HOMA-IR was determined to be an independent risk factor for NAFLD.

PMID- 24119358
TI  - Accurate detection of metabolically active "brown" and "white" adipose tissues
      with computed tomography.
AB  - BACKGROUND: Adipose tissues (AT) are highly metabolically active complex
      endocrine organs and are classified into white (WAT) and brown AT (BAT) with
      proinflammatory and anti-inflammatory characteristics. The current study
      investigated the accuracy of computed tomography (CT) to quantitatively detect
      BAT and WAT based on Hounsfield unit (HU) threshold compared to standardized
      uptake values (SUVs) of corresponding AT with the use of positron emission
      tomography (PET). METHODS: One hundred twenty-four patients who underwent whole
      body (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT were studied. The SUVs and HUs
      of regions of BAT and WAT were measured and compared in these scans. The receiver
      operator characteristic (ROC) analysis was used to detect the HU threshold values
      for the detection of BAT and WAT. RESULTS: The CT HU of BAT, with high (18)F-FDG
      uptake, was significantly higher compared to WAT (-67.1 +/- 8.2 [-10 to -87]
      versus -93.5 +/- 10.1 [-88 to -190], P = .0006). Generalized linear-regression
      models revealed that mean CT HU of BAT was 26.4 HU higher than that of WAT (P =
      .001). A strong agreement between CT HU and PET SUV in measuring metabolically
      active AT (r(2) = 0.81, P = .0001) was observed. The ROC curve showed that the
      optimal cutoff value of CT HU to detect BAT was HU >=-87 with sensitivity of
      83.3% and specificity of 100%, and the negative CT HU below -87 is highly
      specific for WAT. CONCLUSION: In our study, CT can accurately and quantitatively
      detect BAT and WAT based on CT HU threshold, which is -10 to -87 for BAT and -88
      to -190 for WAT.

PMID- 24119359
TI  - Analysis of dominant factors affecting fatigue caused by soft-copy reading.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to analyze the dominant
      factors affecting fatigue caused by soft-copy reading to identify a method for
      decreasing fatigue in clinical practice. MATERIALS AND METHODS: Two types of
      fatigue-fatigue in the central nervous system and subjective visual fatigue-were
      evaluated using a critical fusion frequency test and a questionnaire administered
      to 17 male radiologists before and after soft-copy reading. Reading-induced
      fatigue was assumed to be affected by 20 hypothetical factors associated with
      personal characteristics, time required for reading, content or amount of
      reading, and the reading environment. We used multiple linear regression analysis
      with a variable selection method to detect the best combination of factors
      capable of expressing variations in each of the measured fatigue values. The
      effects of the detected (dominant) factors on fatigue were also examined based on
      coefficients of the dominant factors in multiple regression models. RESULTS:
      Fatigue in the central nervous system decreased with a higher corrected visual
      acuity and a higher ambient illuminance in the reading room and was also affected
      by the type of monitor used. Visual fatigue was relieved when there was a larger
      difference in the brightness of the monitor and the surfaces surrounding the
      monitor and tended to be more severe when glasses rather than contact lenses were
      worn. CONCLUSIONS: Increasing the ambient illuminance, using an appropriate type
      of monitor, improving the corrected visual acuity, and using contact lenses
      rather than eyeglasses could help decrease reading-induced fatigue in male
      radiologists.

PMID- 24119360
TI  - MR imaging findings in colloid cysts of the sellar region: comparison with
      colloid cysts of the third ventricle and Rathke's cleft cysts.
AB  - RATIONALE AND OBJECTIVES: To identify magnetic resonance (MR) imaging
      characteristics allowing specific preoperative discrimination between colloid
      cysts (CCs) of the sellar region and third ventricle (CC3rdv) versus Rathke's
      cleft cysts (RCCs). MATERIALS AND METHODS: MR imaging data of 38 patients with
      histologically proven CCs/CC3rdv and RCC underwent retrospective analysis with
      respect to signal intensity and heterogeneity on T1- and T2-weighted images,
      presence of the dot sign, enhancement, size, location, and accompanying
      infundibular stalk abnormalities. RESULTS: Thirteen patients had CCs, 12 had
      CC3rdv, and 13 had RCCs. Signal intensity on T1-weighted images was partly or
      entirely hyperintense (n = 8), iso- or mixed iso/hypointense (n = 5) in CCs;
      hyperintense (n = 8), isointense, or mixed hypo/isointense (n = 3) in CC3rdv and
      hyperintense (n = 9); or mixed (n = 4) in RCCs. On T2-weighted images, signal
      intensity was hypointense (n = 12) or hyperintense (n = 1) in CCs, hypointense (n
      = 9) or hyperintense (n = 2) in CC3rdv, and hypointense (n = 5) or
      iso/hyperintense (n = 8) in RCCs. T2-weighted images were unavailable in two
      patients. Only one questionable enhancement was found in CCs, whereas an
      enhancing rim was consistently seen in RCCs. The dot sign was present in 7 CCs, 8
      CC3rdv, and 4 RCCs. Mean cyst diameters were 12.6 mm for CCs and 14.5 mm for
      RCCs. RCCs showed more frequent and even solely suprasellar extent contrary to
      CCs. CONCLUSION: Cyst wall enhancement was found in all RCCs but in none of the
      CCs, making this feature a reliable discriminator between the two. Complementary,
      suprasellar extension was more frequent in RCCs, whereas signal hypointensity on
      T2w was more common in colloid cysts.

PMID- 24119361
TI  - Building clinical decision-making skills.

PMID- 24119362
TI  - Diffusion-weighted MR imaging of focal liver lesions in the left and right lobes:
      would visual assessment and/or normalization of ADC be useful for overcoming
      their differences in ADC values resulting from its locations?

PMID- 24119363
TI  - Writing and speaking.

PMID- 24119364
TI  - Comparison of the quality of patient referrals from physicians, physician
      assistants, and nurse practitioners.
AB  - OBJECTIVE: To compare the quality of referrals of patients with complex medical
      problems from nurse practitioners (NPs), physician assistants (PAs), and
      physicians to general internists. PATIENTS AND METHODS: We conducted a
      retrospective comparison study involving regional referrals to an academic
      medical center from January 1, 2009, through December 31, 2010. All 160 patients
      referred by NPs and PAs combined and a random sample of 160 patients referred by
      physicians were studied. Five experienced physicians blinded to the source of
      referral used a 7-item instrument to assess the quality of referrals. Internal
      consistency, interrater reliability, and dimensionality of item scores were
      determined. Differences between item scores for patients referred by physicians
      and those for patients referred by NPs and PAs combined were analyzed by using
      multivariate ordinal logistical regression adjusted for patient age, sex,
      distance of the referral source from Mayo Clinic, and Charlson Index. RESULTS:
      Factor analysis revealed a 1-dimensional measure of the quality of patient
      referrals. Interrater reliability (intraclass correlation coefficient for
      individual items: range, 0.77-0.93; overall, 0.92) and internal consistency for
      items combined (Cronbach alpha=0.75) were excellent. Referrals from physicians
      were scored higher (percentage of agree/strongly agree responses) than were
      referrals from NPs and PAs for each of the following items: referral question
      clearly articulated (86.3% vs 76.0%; P=.0007), clinical information provided
      (72.6% vs 54.1%; P=.003), documented understanding of the patient's
      pathophysiology (51.0% vs 30.3%; P<.0001), appropriate evaluation performed
      locally (60.3% vs 39.0%; P<.0001), appropriate management performed locally
      (53.5% vs 24.1%; P<.0001), and confidence returning patient to referring health
      care professional (67.8% vs 41.4%; P<.0001). Referrals from physicians were also
      less likely to be evaluated as having been unnecessary (30.1% vs 56.2%; P<.0001).
      CONCLUSION: The quality of referrals to an academic medical center was higher for
      physicians than for NPs and PAs regarding the clarity of the referral question,
      understanding of pathophysiology, and adequate prereferral evaluation and
      documentation.

PMID- 24119365
TI  - Metformin-inclusive therapy reduces the risk of stroke in patients with diabetes:
      a 4-year follow-up study.
AB  - Metformin is a kind of oral hypoglycemic agents commonly prescribed to patients
      with diabetes mellitus. Although past studies had proven its protective effect on
      cardiovascular risk and related mortality, the evidence of metformin on stroke
      prevention was still insufficient and conflicting. Our study randomly selected
      14,856 patients with diabetes from the database provided by the Taiwan National
      Health Research Institute, and 2 cohorts were formulated according to whether
      metformin was in the prescription record. All cases were followed up for 4 years
      to track their stroke incidence. As a result, 701 (17.5%) of 3999 diabetic
      patients had stroke without metformin use, whereas 994 (9.2%) of 10,857 patients
      had stroke with metformin use. Cox proportional hazard regressions showed that
      the stroke hazard ratio (HR) of metformin was .383. After adjustment for the
      patients' age, gender, hypertension, atrial fibrillation, hyperlipidemia,
      coronary artery disease, and medications including antiplatelets, coumadin,
      statin, and estrogen use, the HR was still .468. Further stratified analysis
      revealed that metformin had more protective effect in the patients with higher
      risk of stroke. Therefore, metformin should be placed in priority when
      prescribing oral hypoglycemic agents for diabetic patients when considering
      stroke prevention according to our study. 

PMID- 24119366
TI  - Cerebral blood flow and oxygen metabolism measurements using positron emission
      tomography on the first day after carotid artery stenting.
AB  - BACKGROUND: The aim of the present study is the characterization of hemodynamics
      to predict hyperperfusion syndrome (HPS) after carotid artery stenting (CAS) with
      positron emission tomography (PET) obtained before and on the first day after the
      treatment. METHODS: Cerebral perfusion and oxygen metabolism were evaluated by
      (15)O-gas PET in 18 patients with symptomatic internal carotid artery (ICA)
      stenosis before and on the first day after CAS. Regional cerebral blood flow
      (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen
      (CMRO2), and cerebral blood volume (CBV) were measured in the ipsilateral and
      contralateral middle cerebral artery territories and compared between before and
      after CAS. RESULTS: CBF increased in 16 of 18 patients on the first day after CAS
      and postoperative CBF was significantly higher than preoperative CBF bilaterally.
      OEF decreased in 15 of 18 patients on the first day after CAS and postoperative
      OEF was significantly lower than preoperative OEF in the ipsilateral hemisphere.
      CMRO2 and CBV did not change significantly. None of the patients showed HPS after
      CAS. All patients who had preoperative OEF of 53% or more (misery perfusion) in
      the ipsilateral hemisphere showed 50% or more increase in CBF postoperatively.
      The preoperative OEF value significantly correlated with the rate of
      postoperative increase in CBF bilaterally. CONCLUSIONS: CAS increases cerebral
      perfusion and improves hemodynamic compromise in patients with symptomatic ICA
      stenosis. Although we could not clarify the usefulness of PET before and on the
      first day after CAS in predicting HPS, a high preoperative OEF is related to
      postoperative marked CBF increase and might be used as a predictor of HPS.
      Patients with greater hemodynamic compromise with a high preoperative OEF should
      be managed carefully to prevent HPS, but they have a greater chance of CBF
      increase after CAS.

PMID- 24119367
TI  - The utility of middle cerebral artery clot density and burden assessment by
      noncontrast computed tomography in acute ischemic stroke patients treated with
      thrombolysis.
AB  - BACKGROUND: Quantitative and qualitative evaluation of middle cerebral artery
      (MCA) density, together with extent of thrombi, was assessed on plain
      computerized tomography (CT) to delineate better the prognostic value of the
      hyperdense MCA sign (HMCAS) in a cohort of patients who underwent intravenous or
      intra-arterial thrombolysis. METHODS: Density of MCA was quantified by maximum
      pixel-sized measurement of Hounsfield unit (HU) in 105 patients with acute MCA
      proximal segment occlusion, 15 patients with vertebrobasilar circulation stroke
      (VBS) and 44 nonstroke control subjects. Predictive value of HMCAS, absolute HU
      value of within MCA, side-to-side HU ratio, and difference along with a newly
      introduced hyperdense MCA burden score in early dramatic recovery (EDR) and third
      month favorable prognosis were determined with multivariate adjustment for age,
      baseline stroke severity, and thrombus length as measured on CT angiography.
      Receiver operator characteristics (ROC) curves were used to determine the cutoffs
      of quantitative indices to determine HMCAS and their prognostic significance.
      RESULTS: Higher HU was present in the ipsilateral MCA of the patients compared
      with their contralateral side and basilar tip and any MCA of VBS stroke and
      control subjects (area under the curve [AUC] of ROC curves was .753). Symptomatic
      to-asymptomatic HU difference and ratio of MCA stroke were also significantly
      higher than side-to-side difference calculated in VBS stroke and control groups
      (AUC of ROC curves: .770 and .764, respectively). Optimal thresholds of absolute
      HU (44), side-to-side HU difference (2), and ratio (1.0588) showed borderline
      sensitivity and specificity. HMCAS and its quantitative indices were not
      significantly associated with EDR and favorable third-month outcome. Furthermore,
      there was no difference in terms of cardioembolic and atherothrombotic thrombi
      HU. CONCLUSIONS: Utility of the HMCAS as a prognostic marker in stroke
      thrombolysis is not high in the CT angiography era. Previous observation
      regarding its positive prognostic role can be attributed to its association with
      proximal location and extent of clot burden, which are detectable reliably with
      current CT angiography techniques. Neither quantification nor extent of increased
      density seems to have clinical utility for treatment decision making in MCA
      strokes and prediction of emboli composition and response to recanalization
      attempt.

PMID- 24119368
TI  - Decompressive surgery for malignant cerebral venous sinus thrombosis: a
      retrospective case series from Pakistan and comparative literature review.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke in
      the West; however, it is prevalent in Asia and the Middle East. CVST is treated
      with dose-adjusted heparin or heparinoid followed by warfarin to facilitate
      recanalization of venous sinuses. For those with progressive malignant cerebral
      edema, the role of decompressive surgery has been reported from developed
      countries. We present data on decompressive craniectomy from a tertiary care
      stroke center in a developing country and compare our results and population with
      that described in the international literature. METHODS: We retrospectively
      analyzed data of all patients who underwent a decompressive hemicraniectomy for
      CVST at the Aga Khan University Hospital, Karachi, Pakistan from 1999 till 2011.
      A record review of the Aga Khan University Hospital was performed as
      decompressive hemicraniectomy for malignant CVST is not being performed elsewhere
      in the country and the hospital is a major referral center. Using the
      International Classification of Diseases, Ninth Edition codes for CVST, we
      identified a total of 7 patients. Patients are presented along with descriptions
      of their presentation, neuroimaging, intraoperative findings, and long-term
      outcomes. Pearson chi-square test was done to identify features that predicted
      survival. A comparative literature review was also done through PubMed to
      identify all other reports of surgery for CVST. RESULTS: During a 12-year review,
      134 patients were diagnosed with CVST. Of these, 7 received intervention. The age
      range of the patients was 15-60 years. Four of the 7 patients had an excellent
      outcome, 2 of 7 died, and 1 of 7 left against medical advice (in a comatose
      state) and was lost to follow-up. Patients presented alert but progressively
      deteriorated preoperatively. All those patients who had preoperative reactive
      pupils with low Glasgow Coma Scale scores made a complete neurologic recovery,
      and patients with fixed, dilated, and nonreactive pupils preoperatively died in
      the first postoperative week (P = .05). CONCLUSIONS: Patients who received
      decompressive hemicraniectomy in Pakistan for CVST had excellent outcomes in all
      cases when intervention was performed with intact preoperative pupillary
      reflexes. Of the data reviewed, most reported (two-third) patients show the same
      prognosticators; however, one third show that even with nonreactive pupils
      complete recovery is possible.

PMID- 24119369
TI  - Outcomes of distal humerus fractures in patients above 65 years of age treated by
      plate fixation.
AB  - INTRODUCTION: Distal humerus fractures in elderly patients are often complex
      fractures that are difficult to treat. The goal of this study was to report on
      the results of a multicentre series of internal fixation of AO type A, B and C
      distal humerus fractures in elderly patients and to identify the pros and cons of
      various fixation constructs. PATIENTS AND METHODS: Two studies were performed.
      One was a prospective multicentre study with 53 patients and the other was a
      retrospective multicentre study with 289 patients, all above 65 years of age and
      with a recent distal humerus fracture. Patients were evaluated based on clinical
      criteria (history, health condition, joint range of motion, Mayo Elbow
      Performance Score) and radiological criteria (fracture type, union of fracture,
      presence of malunion, hardware condition). RESULTS: Based on the MEPS, the
      clinical and functional results were relatively satisfactory: average of 92
      points for type A, 82 points for type B and 88 points for type C. In both series,
      type B fractures were the most difficult to treat and had less good clinical,
      functional and radiological outcomes. Most of the complications occurred with
      type C fractures; these consisted mainly of nerve injuries and fixation
      failure/non-union. DISCUSSION: Although these fractures are difficult to treat
      and have an appreciable number of complications, the functional recovery was
      fairly satisfactory. One of the most challenging aspects of surgical treatment is
      the existence of osteoporosis in these patients. This must be carefully analysed
      to determine if an indication exists for total elbow arthroplasty. LEVEL OF
      EVIDENCE: IV.

PMID- 24119370
TI  - Saikosaponin-d increases the radiosensitivity of smmc-7721 hepatocellular
      carcinoma cells by adjusting the g0/g1 and g2/m checkpoints of the cell cycle.
AB  - BACKGROUND: Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese
      herbal drug Radix bupleuri, has multiple effects, including anticancer
      properties. However, the effect of SSd on tumors exposed to radiation is largely
      unknown. To investigate the radiosensitizing effect of SSd and its possible
      mechanism, we combined SSd with radiation therapy to treat SMMC-7721
      hepatocellular carcinoma cells under oxia and hypoxia. METHODS: Cell growth,
      apoptosis, and cell cycle distribution were examined after treatment with SSd
      alone, radiation alone, and their combinations under oxia and hypoxia. The
      protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot
      analysis and RT-PCR, respectively. RESULTS: Treatment with SSd alone and
      radiation alone inhibited cell growth and increased apoptosis rate at the
      concentration used. These effects were enhanced when SSd was combined with
      radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1
      arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia.
      However, under oxia, SSd only potentiated the effects of radiation to induce
      G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation
      alone, and their combination, were accompanied by upregulated expression of p53
      and BAX and downregulation of Bcl2 expression under oxia and hypoxia. CONCLUSION:
      SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a
      promising radiosensitizer. The radiosensitizing effect of SSd may contribute to
      its effect on the G0/G1 and G2/M checkpoints of the cell cycle.

PMID- 24119371
TI  - Explaining significant differences in subjective and objective measures of
      cardiovascular health: evidence for the socioeconomic gradient in a population
      based study.
AB  - BACKGROUND: To assess prevalence rates of subjective and objective reports of two
      cardiovascular disorders (hypertension and hypercholesterolemia) for the same
      subset of respondents in a large-scale study. To determine whether and the extent
      to which the socioeconomic health gradient differed in the subjective and
      objective reports of the two cardiovascular disorders. METHODS: Data from the
      first wave (2009/2011) of The Irish Longitudinal Study on Ageing were used (n =
      4,179). This is a nationally representative study of community-dwelling adults
      aged 50+ residing in Ireland. Subjective measures were derived from self-reports
      of doctor-diagnosed hypertension and high cholesterol. Objective measure of
      hypertension was defined as: systolic blood pressure >=140 mm Hg and/or diastolic
      blood pressure >=90 mm Hg and/or on antihypertensive medication. Objective
      measure of hypercholesterolemia was defined as: total cholesterol >=5.2 mmol/L
      and/or on cholesterol-lowering medication. Objective measures of low-density
      lipoprotein cholesterol and high-density-lipoprotein cholesterol were also used.
      Two measures of socioeconomic gradient were employed: education and wealth.
      Binary and multinomial logistic and linear regression analyses were used.
      Analyses were adjusted for an extensive battery of covariates, including
      demographics and measures of physical/behavioural health and health care
      utilization. RESULTS: Prevalence of cardiovascular disorders: prevalence of
      hypertension and hypercholesterolemia was significantly higher when the
      cardiovascular disorders were measured objectively as compared to self-reports
      (64% and 72.1% versus 37% and 41.1%, respectively). Socioeconomic gradient in
      hypertension: the odds of being objectively hypertensive were significantly lower
      for individuals with tertiary/higher education (OR, 0.74; 95% CI, 0.60-0.92) and
      in the highest tertile of the wealth distribution (OR, 0.77; 95% CI, 0.62-0.95).
      In contrast, the associations between socioeconomic status and self-reported
      hypertension were not statistically significant. Socioeconomic gradient in
      hypercholesterolemia: wealthier individuals had higher odds of self-reporting
      elevated cholesterol (OR, 1.28; 95% CI, 1.03-1.58). Associations between
      socioeconomic status and objectively measured hypercholesterolemia and low
      density-lipoprotein cholesterol were not significant. Higher education and, to a
      lesser extent, greater wealth were associated with higher levels of high-density
      lipoprotein cholesterol. CONCLUSIONS: Clear discrepancies in prevalence rates and
      gradients by socioeconomic status were found between subjective and objective
      reports of both disorders. This emphasizes the importance of objective measures
      when collecting population data.

PMID- 24119372
TI  - Nitric oxide synthase mediates PC12 differentiation induced by the surface
      topography of nanostructured TiO2.
AB  - BACKGROUND: Substrate nanoscale topography influences cell proliferation and
      differentiation through mechanisms that are at present poorly understood. In
      particular the molecular mechanism through which cells 'sense' and adapt to the
      substrate and activate specific intracellular signals, influencing cells survival
      and behavior, remains to be clarified. RESULTS: To characterize these processes
      at the molecular level we studied the differentiation of PC12 cells on
      nanostructured TiO2 films obtained by supersonic cluster beam deposition.Our
      findings indicate that, in PC12 cells grown without Nerve Growth Factor (NGF),
      the roughness of nanostructured TiO2 triggers neuritogenesis by activating the
      expression of nitric oxide synthase (NOS) and the phospho-extracellular signal
      regulated kinase 1/2 (pERK1/2) signaling. Differentiation is associated with an
      increase in protein nitration as observed in PC12 cells grown on flat surfaces in
      the presence of NGF. We demonstrate that cell differentiation and protein
      nitration induced by topography are not specific for PC12 cells but can be
      regarded as generalized effects produced by the substrate on different neuronal
      like cell types, as shown by growing the human neuroblastoma SH-SY5Y cell line on
      nanostructured TiO2. CONCLUSION: Our data provide the evidence that the nitric
      oxide (NO) signal cascade is involved in the differentiation process induced by
      nanotopography, adding new information on the mechanism and proteins involved in
      the neuritogenesis triggered by the surface properties.

PMID- 24119373
TI  - Effect of Curcumin on the metal ion induced fibrillization of amyloid-beta
      peptide.
AB  - The effect of Curcumin on Cu(II) and Zn(II) induced oligomerization and
      protofibrillization of the amyloid-beta (Abeta) peptide has been studied by
      spectroscopic and microscopic methods. Curcumin could significantly reduce the
      beta-sheet content of the peptide in a time dependent manner. It also plays an
      antagonistic role in beta-sheet formation that is promoted by metal ions like
      Cu(II) and Zn(II) as observed by Circular Dichroism (CD) spectroscopy. Atomic
      force microscopic (AFM) images show that spontaneous fibrillization of the
      peptide occurs in presence of Cu(II) and Zn(II) but is inhibited on incubation of
      the peptide with Curcumin indicating the beneficial role of Curcumin in
      preventing the aggregation of Abeta peptide. 

PMID- 24119374
TI  - Influence of the composition of the initial mixtures on the chemical composition,
      physicochemical properties and humic-like substances content of composts.
AB  - The influence of the proportion of C- and N-rich raw materials (initial C/N
      ratio) and bulking agent on the chemical functional groups composition, humic
      like substances (HS-like) content and physicochemical properties of composts was
      assessed. To achieve these goals, seven initial mixtures (BA1-6 and C1) of dog
      food (N-rich raw material) were composted with wheat flour (C-rich raw material).
      Composts were analyzed in terms of chemical functional groups, physicochemical,
      maturity and stability parameters. The C-rich raw material favored the formation
      of oxidized organic matter (OM) during the composting process, as suggested by
      the variation of the ratios of the peaks intensity of FT-IR spectra,
      corresponding to a decrease of the polysaccharides and an increase of aromatic
      and carboxyl-containing compounds. However, although with high proportion of C
      rich raw material, mixtures with low initial C/N seems to have favored the
      accumulation of partially oxidized OM, which may have contributed to high
      electrical conductivity values in the final composts. Therefore, although
      favoring the partial transformation of OM into stabilized HS-like, initial
      mixtures with high proportion of C-rich raw material but with low initial C/N led
      to unstable composts. On the other hand, as long as a high percentage of bulking
      agent was used to promote the structure of biomass and consequently improve of
      the aeration conditions, low initial C/N was not a limiting factor of OM
      oxidation into extractable stabilized humic-like acids. 

PMID- 24119376
TI  - The prevalence and incidence, resource use and financial costs of treating people
      with attention deficit/hyperactivity disorder (ADHD) in the United Kingdom (1998
      to 2010).
AB  - BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common disorder
      that often presents in childhood and is associated with increased healthcare
      resource use. The aims of this study were to characterise the epidemiology of
      diagnosed ADHD in the UK and determine the resource use and financial costs of
      care. METHODS: For this retrospective, observational cohort study, patients newly
      diagnosed with ADHD between 1998 and 2010 were identified from the UK Clinical
      Practice Research Datalink (CPRD) and matched to a randomly drawn control group
      without a diagnosis of ADHD. The prevalence and incidence of diagnosed ADHD were
      calculated. Resource utilisation and corresponding financial costs post-diagnosis
      were estimated for general practice contacts, investigations, prescriptions,
      outpatient appointments, and inpatient admissions. RESULTS: Incidence of
      diagnosed ADHD (and percentage change using 1998 as a reference) increased from
      6.9 per 100,000 population in 1998 to 12.2 per 100,000 (78%) in 2007 and then
      fell to 9.9 per 100,000 (44%) by 2009. The corresponding prevalence figures were
      30.5, 88.9 (192%) and 81.5 (167%) per 100,000. Incidence and prevalence were
      higher in males than females. Mean annual total healthcare costs were higher for
      ADHD cases than controls (L1,327 versus L328 for year 1, L1,196 vs. L337 for year
      2, L1,148 vs. L316 for year 3, L1,126 vs. L325 for year 4, and L1,112 vs. L361
      for year 5). CONCLUSIONS: The prevalence of diagnosed ADHD in routine practice in
      the UK was notably lower than in previous reports, and both prevalence and
      incidence of diagnosed ADHD in primary care have fallen since 2007. Financial
      costs were more than four times higher in those with ADHD than in those without
      ADHD.

PMID- 24119375
TI  - Roles and effectiveness of lay community health workers in the prevention of
      mental, neurological and substance use disorders in low and middle income
      countries: a systematic review.
AB  - BACKGROUND: It has been suggested that lay community health workers (LHWs) could
      play a role in primary and secondary prevention of Mental, Neurological and
      Substance use (MNS) disorders in low resourced settings. We conducted a
      systematic review of the literature with the aim of assessing the existing
      evidence base for the roles and effectiveness of LHWs in primary and secondary
      prevention of MNS disorders in low and middle income countries (LMICs). METHODS:
      Internet searches of relevant electronic databases for articles published in
      English were done in August 2011 and repeated in June 2013. Abstracts and full
      text articles were screened according to predefined criteria. Authors were asked
      for additional information where necessary. RESULTS: A total of 15 studies, 11 of
      which were randomised, met our inclusion criteria. Studies were heterogeneous
      with respect to interventions, outcomes and LHWs' roles. Reduction in symptoms of
      depression and improved child mental development were the common outcomes
      assessed. Primary prevention and secondary prevention strategies were carried out
      in 11 studies and 4 studies respectively .There was evidence of effectiveness of
      interventions however, most studies (n = 13) involved small sample sizes and all
      were judged to have an unclear or high risk of bias. CONCLUSIONS: LHWs have the
      potential to provide psychosocial and psychological interventions as part of
      primary and secondary prevention of MNS disorders in LMICs, but there is
      currently insufficient robust evidence of effectiveness of LHW led preventive
      strategies in this setting. More studies need to be carried out in a wider range
      of settings in LMICs that control for risk of bias as far as possible, and that
      also collect indicators relating to the fidelity and cost of interventions.

PMID- 24119377
TI  - Perceptions of patients, physicians, and Medical students on physicians'
      appearance.
AB  - OBJECTIVE: To investigate the impressions made by different styles of dress and
      appearance adopted by physicians on patients, medical students and other
      physicians in Brazil. METHODS: Two hundred fifty nine patients, 119 students, and
      99 physicians answered questions related to a panel of male and female
      physicians' pictures covering the following styles: white clothing; white coat;
      formal, informal, and casual garments; and surgical scrubs. They also reported
      their level of discomfort with a list of 20 items for professional appearance of
      both genders. RESULTS: Most of the answers of the volunteers involved using white
      clothes or white coat, and in many situations the percentages of preference
      referred for these styles were close. Physicians and students preferred
      physicians wearing surgical scrubs for emergency visits, and doctors with
      informal style for discussing psychological problems with male professionals.
      Patients most often chose white clothing in response to questions. Regarding male
      professionals, all three groups reported high degree of discomfort for the use of
      shorts and bermuda shorts, multiple rings, facial piercing, sandals, extravagant
      hair color, long hair, and earrings. For females, high levels of discomfort were
      reported to shorts, blouses exposing the belly, facial piercing, multiple rings,
      extravagant hair color, and heavy makeup. CONCLUSION: Brazilian patients,
      physicians, and medical students form a better initial impression of physicians
      using clothing traditionally associated with the profession and exhibiting more
      conventional appearance. The use of entirely white garments appears to be a
      satisfactory option in this country.

PMID- 24119378
TI  - Clinical and autonomic profile of patients with Alzheimer's disease and mixed
      dementia patients.
AB  - OBJECTIVE: To analyze the clinical and autonomical profile of patients with
      Alzheimer's disease or mixed dementia (MD). METHODS: Fifty-four patients with
      indication for cholinesterase inhibitors use were evaluated through clinical
      examination, rest electrocardiogram, and spectral analysis of heart rate (HR)
      variability through digital Holter system recordings. RESULTS: Overall, 61.1% of
      patients were female and were, on average, 77.1 years of age, 3.3 years of
      schooling and scored 16.4 points on the Mini Mental State Examination. The gap
      between symptom onset and diagnosis was 26.2 months. Almost all patients (90.7%)
      presented at least one clinical comorbidity, and each patient took, on average,
      3.7 drugs to control them. Thirty-one patients had some alteration on the
      electrocardiogram and nine (16.6%) had orthostatic hypotension (OH). The latter
      was associated with the diagnosis of MD (p=0.001), with lower values of low (LF)
      and high (HF) frequency components of the spectral analysis in the supine
      position (p=0.000 and p=0.017, respectively) and with lower values of LF in the
      orthostatic position (p=0.006). Diagnosis of MD was associated with lower values
      of LF in both positions (p=0.003 and p=0.007). CONCLUSION: This sample of
      patients had frequent comorbidities, which resulted in the prescription of
      multiple drugs. Signs of autonomic dysfunction resulting in OH were found mainly
      in those with MD.

PMID- 24119379
TI  - Laser therapy in the control of oral mucositis: a meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis of the effectiveness
      of Laser Therapy in the prevention of oral mucositis (OM) in patients undergoing
      oncotherapy. METHODS: To this systematic review and meta-analysis a search was
      performed in MEDLINE, LILACS and Cochrane using the keywords "laser therapy" and
      "Oral mucostitis." The case-control studies included were submitted to odds ratio
      (OR) analysis, which the cut-off point for statistic calculation was OM grade >
      3. We carried out a meta-analysis by BioEstat 5.0, using the Random Effect
      DerSimonian-Laird statistical analysis. RESULTS: Twelve (studies were included in
      this systematic review, and the meta-analysis of seven of them showed that LT in
      patients undergoing oncotherapy is approximately nine times more effective in the
      prevention of OM grade > 3 than in patients without laser treatment (OR: 9,5281,
      confidence interval 95% 1,447-52,0354, p=0,0093. CONCLUSION: These data
      demonstrated significant prophylatic effect of OM grade > 3 in patients
      undergoing LT. Further studies, with larger sample sizes, are needed for better
      evaluation of the prophylatic effect of OM grade > 3 by LT.

PMID- 24119380
TI  - Validity of the methods to assess body fat in children and adolescents using
      multi-compartment models as the reference method: a systematic review.
AB  - OBJECTIVE: To analyze the validity of methods to assess body fat in children and
      adolescents using a systematic review. METHODS: The search was conducted by two
      independent researchers using the MEDLINE, BioMed Central, SciELO and LILACS
      electronic databases. For inclusion, the articles should be written in English or
      Portuguese, and must have used multi-compartment models as the criterion measure
      of the model, with body fat measurement of whole body in non-athlete children and
      adolescents. RESULTS: A preliminary search resulted in 832 studies. After all
      selection steps were performed, 12 articles were included. The selected studies
      were published between 1997 and 2010, whose samples consisted of children and
      adolescents with levels of relative body fat ranging from 20.7% to 41.4%. The
      methods used were: dual energy X-ray absorptiometry (58.3%), isotope dilution
      (41.6%), skinfold thickness (33.3%), hydrostatic weighing (25%), bioelectrical
      impedance analysis (25%), air displacement plethysmography (16.6%), and total
      body electrical conductivity (8.3%). CONCLUSIONS: Based on the analysis of the
      studies, isotope dilution and air displacement plethysmography methods were the
      most reliable, despite the limited number of studies. As for clinical use or for
      population-based studies, the equation of Slaughter et al. (1998), which uses the
      triceps and subscapular skinfolds thickness, showed the best results for
      assessment of body fat in this population.

PMID- 24119381
TI  - Urodynamic assessment of bladder and urethral sphincter function before and after
      robot-assisted radical prostatectomy.
AB  - INTRODUCTION: Affectation of the bladder after open prostatectomy is
      demonstrated. Decrease in bladder capacity and bladder compliance, detrusor hyper
      or hypo-activity and voiding dysfunction are observed. We propose to investigate
      the effects of robotic surgery on bladder and sphincter function through the
      comparative study of preoperative and postoperative urodynamic values 3 months
      after prostatectomy. MATERIAL AND METHODS: Prospective study of 32 consecutive
      patients undergoing robotic prostatectomy. They all underwent urodynamic study
      one month before the intervention and 3 months after the radical prostatectomy.
      RESULTS: Twenty five percent of patients undergoing robotic prostatectomy showed
      detrusor hyperactivity accompanied by a decrease in bladder compliance of 30.2 to
      21.8 ml/cmH2O. Urethral profile showed diminished functional length of 67 to 44
      mm and decreased maximum urethral pressure of 48.5 to 29.3 cmH2O. After robotic
      prostatectomy 21.8% of patients had detrusor hypoactivity, obstruction decreased
      between 28.1% to 12.5%. CONCLUSIONS: Decreased bladder compliance, detrusor hypo-
      or hyperactivity and obstruction improvement observed in the study of the flow
      pressure have been associated with sphincter involvement. It is part of the
      complex of lower urinary tract dysfunction that occurs after robotic
      prostatectomy.

PMID- 24119382
TI  - Therapeutic benefit in patients switching tolterodine to other novel
      antimuscarinic agents.
AB  - OBJECTIVES: To explore in the daily clinical practice setting that
      antimuscarinic, Fesoterodine or Solifenacin, provides a greater clinical benefit
      after changing their prior Overactive Bladder (OAB) therapy with tolterodine
      extended-release (ER) to other novel antimuscarinic agents. MATERIAL AND METHODS:
      A post-hoc analysis of data from an observational multicenter, cross-sectional,
      retrospective study. Adult patients of both sexes, with OAB and OAB-V8 score>=8,
      who switched to fesoterodine or solifenacin within the 3-4 months before study
      visit from their prior tolterodine-ER-based therapy due to poor response were
      included. 92 patients were selected for each treatment group, matched (1:1)
      according to conditioned probability using the propensity score. Benefit of
      treatment change perceived by the physician and patient was evaluated by means of
      the Clinical Global Impression of Improvement subscale (CGI-I) and Treatment
      Benefit Scale (TBS), respectively. Degree of worry, bother and interference with
      daily living activities due to urinary symptoms, level of satisfaction, and
      preference for current treatment were also assessed. RESULTS: Fesoterodine
      provided a significantly greater improvement than solifenacina in terms of
      therapeutic benefit perceived by the physician according to ICG-I. 96.7% of the
      patients on fesoterodine treatment vs. 81.6% of the solifenacin group showed a
      score of improvement in TBS (P<.05). Fesoterodine was also better rated than
      solifenacin with regard to satisfaction and preference for the new treatment
      (93.4 vs. 78.2% P<.05). CONCLUSIONS: In daily clinical practice the switch from
      tolterodine LP to fesoterodine seems to provide greater benefits both from the
      physician's and the patient's point of view compared with those provided by
      solifenacin.

PMID- 24119383
TI  - Chronic cerebrospinal venous insufficiency in multiple sclerosis: the final
      curtain.

PMID- 24119384
TI  - Prevalence of extracranial venous narrowing on catheter venography in people with
      multiple sclerosis, their siblings, and unrelated healthy controls: a blinded,
      case-control study.
AB  - BACKGROUND: Chronic cerebrospinal venous insufficiency has been proposed as a
      unique combination of extracranial venous blockages and haemodynamic flow
      abnormalities that occurs only in patients with multiple sclerosis and not in
      healthy people. Initial reports indicated that all patients with multiple
      sclerosis had chronic cerebrospinal venous insufficiency. We aimed to establish
      the prevalence of venous narrowing in people with multiple sclerosis, unaffected
      full siblings, and unrelated healthy volunteers. METHODS: We did an assessor
      blinded, case-control, multicentre study of people with multiple sclerosis,
      unaffected siblings, and unrelated healthy volunteers. We enrolled the study
      participants between January, 2011 and March, 2012, and they comprised 177
      adults: 79 with multiple sclerosis, 55 siblings, and 43 unrelated controls, from
      three centres in Canada. We assessed narrowing of the internal jugular and
      azygous veins with catheter venography and ultrasound criteria for chronic
      cerebrospinal venous insufficiency proposed by Zamboni and colleagues. Catheter
      venography data were available for 149 participants and ultrasound data for 171
      participants. FINDINGS: Catheter venography criteria for chronic cerebrospinal
      venous insufficiency were positive for one of 65 (2%) people with multiple
      sclerosis, one of 46 (2%) siblings, and one of 32 (3%) unrelated controls (p=1.0
      for all comparisons). Greater than 50% narrowing of any major vein was present in
      48 of 65 (74%) people with multiple sclerosis, 31 of 47 (66%) siblings (p=0.41
      for comparison with patients with multiple sclerosis), and 26 of 37 (70%)
      unrelated controls (p=0.82). The ultrasound criteria for chronic cerebrospinal
      venous insufficiency were fulfilled in 35 of 79 (44%) participants with multiple
      sclerosis, 17 of 54 (31%) siblings (p=0.15 for comparison with patients with
      multiple sclerosis) and 17 of 38 (45%) unrelated controls (p=0.98). The
      sensitivity of the ultrasound criteria for detection of greater than 50%
      narrowing on catheter venography was 0.406 (95% CI 0.311-0.508), and specificity
      was 0.643 (0.480-0.780). INTERPRETATION: This study shows that chronic
      cerebrospinal venous insufficiency occurs rarely in both patients with multiple
      sclerosis and in healthy people. Extracranial venous narrowing of greater than
      50% is a frequent finding in patients with multiple sclerosis, unaffected
      siblings, and unrelated controls. The ultrasound criteria are neither sensitive
      nor specific for narrowing on catheter venography. The significance of venous
      narrowing to multiple sclerosis symptomatology remains unknown. FUNDING: MS
      Society of Canada, Saskatoon City Hospital Foundation, Lotte and John Hecht
      Memorial Foundation, Vancouver Coastal Health Foundation, and the Wolridge
      Foundation.

PMID- 24119385
TI  - Ultrasound-guided shoulder MR arthrography: comparison of rotator interval and
      posterior approach.
AB  - PURPOSE: The purpose of this study was to prospectively evaluate the two
      different ultrasound-guided injection techniques for magnetic resonance (MR)
      arthrography of the shoulder. METHODS AND MATERIALS: This study included 100
      patients [50 rotator interval group (n=50) vs. 50 posterior approach group
      (n=50)]. All procedures were performed by the same radiologist. The two injection
      techniques were compared. The discomfort during and after arthrography was
      evaluated. Extraarticular contrast media extravasation was graded according to
      the MRI findings. The number of injection attempts, effect of contrast media
      extravasation rate on diagnostic quality and procedure times were recorded.
      RESULTS: There were no significant difference between the posterior and rotator
      interval puncture groups with regard to pain (P=.915), procedure times (P=.401)
      or attempt scores (P=.182). There were significantly more contrast media
      extravasations with rotator interval approach than posterior approach (P<.05).
      CONCLUSION: Both techniques were successful and well tolerated by patients.
      Posterior injection technique provided a more effective route with decreased
      extravasation rate and easier approach compared to the rotator interval approach.

PMID- 24119387
TI  - Clonal spread of Salmonella enterica serovar Infantis in Serbia: acquisition of
      mutations in the topoisomerase genes gyrA and parC leads to increased resistance
      to fluoroquinolones.
AB  - Quinolone-resistant Salmonella Infantis (n = 64) isolated from human stool
      samples, food and poultry during the years 2006-2011 were analysed for their
      resistance phenotypes, macrorestriction patterns and molecular mechanisms of
      decreased susceptibility to fluoroquinolones. Minimum inhibitory concentrations
      (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were determined by the
      agar dilution procedure, and the susceptibility to additional antimicrobial
      agents was determined by the disc diffusion method. To assess the influence of
      enhanced efflux activity, MICs were determined in the presence and absence of the
      inhibitor PAbetaN. The results of pulsed-field gel electrophoresis (PFGE) typing
      revealed that quinolone-resistant S. Infantis in Serbia had similar or
      indistinguishable PFGE profiles, suggesting a clonal spread. All S. Infantis
      showed combined resistance to NAL and tetracycline, whereas multiple drug
      resistance to three or more antibiotic classes was rare (2 isolates of human
      origin). The MICs ranged between 512 and 1024 MUg/mL for NAL and 0.125-2 MUg/mL
      for CIP. A single-point mutation in the gene gyrA leading to a Ser83->Tyr
      exchange was detected in all isolates, and a second exchange (Ser80->Arg) in the
      gene parC was only present in eight S. Infantis isolates exhibiting slightly
      higher MICs of CIP (2 MUg/mL). The inhibitor PAbetaN decreased the MIC values of
      CIP by two dilution steps and of NAL by at minimum 3-6 dilution steps, indicating
      that enhanced efflux plays an important role in quinolone resistance in these
      isolates. The plasmid-mediated genes qnr, aac(6')-lb-cr and qepA were not
      detected by PCR assays.

PMID- 24119386
TI  - Improvement of the quality of BRAF testing in melanomas with nationwide external
      quality assessment, for the BRAF EQA group.
AB  - BACKGROUND: Knowledge about tumour gene mutation status is essential for the
      treatment of increasing numbers of cancer patients, and testing quality has a
      major impact on treatment response and cost. In 2012, 4,629 tests for BRAF p.V600
      were performed in France, in patients with melanomas. METHODS: Two batches of
      unstained melanoma sections were sent, in May and November 2012, to the 46
      laboratories supported by the French National Institute of Cancer (INCa). An
      external quality assessment (EQA) evaluated mutation status, response times and
      compliance with INCa recommendations. RESULTS: All the French laboratories
      involved in testing participated in the EQA. Fourteen different methods were used
      to detect BRAF mutations, most consisting of combinations of in-house techniques.
      False responses were noted in 25/520 cases (4.8%), 11 of which concerned
      confusion between p.V600E and p.V600K. Thus, 2.7% of responses would have led to
      inappropriate treatment. Within six months, mean response times decreased from 22
      to 12 days (P<0.001), and the percentage of samples evaluated by a pathologist
      for tumour cell content increased, from 75.2% to 96.9% (P<0.001). CONCLUSION:
      Despite the use of non-certified methods, the false response rate was low.
      Nationwide EQA can improve the quality of molecular pathology tests on tumours.

PMID- 24119388
TI  - Shared learning in an interconnected world: innovations to advance global health
      equity.
AB  - The notion of "reverse innovation"--that some insights from low-income countries
      might offer transferable lessons for wealthier contexts--is increasingly common
      in the global health and business strategy literature. Yet the perspectives of
      researchers and policymakers in settings where these innovations are developed
      have been largely absent from the discussion to date. In this Commentary, we
      present examples of programmatic, technological, and research-based innovations
      from Rwanda, and offer reflections on how the global health community might
      leverage innovative partnerships for shared learning and improved health outcomes
      in all countries. 

PMID- 24119389
TI  - Comparison of graft healing in anterior cruciate ligament reconstruction with and
      without a preserved remnant in rabbits.
AB  - BACKGROUND: The remnant of the native anterior cruciate ligament (ACL) might
      contribute to the biological integration of the graft in ACL reconstruction. The
      aim of this study was to explore whether the preserved remnant enhanced graft
      healing in ACL reconstruction. METHODS: Forty New Zealand rabbits underwent
      bilateral anterior cruciate ligament reconstructions. One knee was treated with a
      2-mm remnant preserved on the tibial side (remnant-preservation, RP group) while
      the contralateral knee underwent a complete removal of the remnants by
      cauterization (remnant-resection, RR group) in each animal. Gross observations
      combined with microangiography, histological evaluation, and uniaxial load
      testing were performed after 4, 8, and 12weeks. RESULTS: The vascular density on
      the graft surface was statistically higher in the RP group as compared to that of
      the RR group at 4 (P=0.002) and 8weeks (P=0.020). Additionally, the accelerated
      intra-articular and intra-tunnel graft integration were histologically observed
      in the RP group. Histological scores in the RP group were statistically higher
      than the RR group at 4weeks (P=0.028 for the intra-articular healing and P=0.046
      for the intra-tunnel healing) and 8weeks (P=0.031 for the intra-articular healing
      and P=0.014 for the intra-tunnel healing). The ultimate failure load (P=0.017),
      yield load (P=0.025), and stiffness (P=0.004) were statistically higher in the RP
      group as compared to those of the RR group, with corresponding significant
      differences in the failure mode (P=0.020) between the two groups at 8weeks.
      CONCLUSIONS: The preserved remnant enhanced ACL graft healing with improved
      biomechanical properties in the rabbit model. LEVEL OF EVIDENCE: Level II.

PMID- 24119390
TI  - Do callers to the NSW Sexual Health Infoline attend the services they are
      referred to?
AB  - BACKGROUND: The NSW Sexual Health Infoline (SHIL) is a free and confidential
      sexual health information and referral line. The ability of Australian sexual
      health helplines to facilitate successful referrals has not been studied. In the
      present study, we sought to determine whether callers were successful in
      accessing the publicly funded sexual health services (PFSHS) or general
      practitioners (GP) they were referred to. METHODS: Callers to SHIL who were
      directly referred to a PFSHS or GP for HIV and/or sexually transmissible
      infection testing from 3 January to 31 March 2012 were offered a follow-up phone
      call 1 week later. RESULTS: Of 474 eligible callers, 190 (40%) agreed to disclose
      a first name and contact details and to be contacted by a study nurse on an
      agreed-upon date. One hundred and twenty (63%) callers were successfully
      contacted 1 week later; of these, 85% had attended or had a future appointment
      booked for testing. CONCLUSIONS: We conclude that among the study sample that was
      successfully followed up, most callers to the SHIL had attended or booked
      appointments to the services they were referred to.

PMID- 24119391
TI  - Linear and nonlinear analysis of normal and CAD-affected heart rate signals.
AB  - Coronary artery disease (CAD) is one of the dangerous cardiac disease, often may
      lead to sudden cardiac death. It is difficult to diagnose CAD by manual
      inspection of electrocardiogram (ECG) signals. To automate this detection task,
      in this study, we extracted the heart rate (HR) from the ECG signals and used
      them as base signal for further analysis. We then analyzed the HR signals of both
      normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii)
      nonlinear techniques. The following are the nonlinear methods that were used in
      this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters,
      Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher
      Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode
      Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the
      analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD
      subjects. We have also observed significant variations in the range of these
      features with respect to normal and CAD classes, and have presented the same in
      this paper. We found that the RQA parameters were higher for CAD subjects
      indicating more rhythm. Since the activity of CAD subjects is less, similar
      signal patterns repeat more frequently compared to the normal subjects. The
      entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating
      lower entropy (less activity due to impairment) for CAD. Almost all HOS
      parameters showed higher values for the CAD group, indicating the presence of
      higher frequency content in the CAD signals. Thus, our study provides a deep
      insight into how such nonlinear features could be exploited to effectively and
      reliably detect the presence of CAD. 

PMID- 24119392
TI  - Cardiovascular morbidity-mortality associated to ankle-brachial index in the
      general population.
AB  - BACKGROUND AND OBJECTIVES: Abnormal ankle-brachial index (ABI) is associated with
      a high risk of cardiovascular disease. This study has aimed to investigate the
      association between low ABI and risk of cardiovascular death in a general
      population attended in a primary care center. PATIENTS AND METHODS: A total of
      1,361 volunteers aged between 60 and 79 years without any evidence of peripheral
      artery disease who attended a primary care center participated in the study. They
      underwent a complete physical examination, together with standard blood tests and
      ABI was determined. The participants were contacted by telephone 4 years later
      and asked about any cardiovascular problems for that period. Causes of death and
      hospitalization were confirmed in the medical records in the primary care center
      and/or hospital. RESULTS: Information was obtained about the clinical evolution
      of 1,300 participants (mean age 69.9 years, 38.2% men). Mean follow-up was 49.8
      months. There were 13 cardiovascular death and 49 major cardiovascular events.
      Low ABI (<0.9) was associated with a significant higher risk of cardiovascular
      death (adjusted relative risk 6.83; 95% confidence interval 1.36-34.30, P=.020),
      and with a higher risk of major cardiovascular events (adjusted relative risk
      2.42; 95% confidence interval 0.99-5.91, P=.051). High or uncompressible ABI was
      not associated with higher cardiovascular risk. CONCLUSIONS: A low ABI was
      associated with higher risk of cardiovascular death in the general population
      followed-up in a primary care center.

PMID- 24119393
TI  - Guidelines on the management of implantable cardioverter defibrillators at the
      end of life.
AB  - This article is a joint document of the Spanish Society of Geriatrics and
      Gerontology, the Spanish Society of Palliative Care and the Section of Geriatric
      Cardiology of the Spanish Society of Cardiology. Its aim is to address the huge
      gap that exists in Spain with regard to the management of implantable
      cardioverter defibrillators (ICDs) in the final stages of life. It is
      increasingly common to find patients carrying these devices that are in the
      terminal stage of an advanced disease. This occurs in patients with advanced
      heart disease and subsequent heart failure refractory to treatment but also in a
      patient with an ICD who develops cancer disease, organ failure or other
      neurodegenerative diseases with poor short-term prognosis. The vast majority of
      these patients are over 65, so the paper focuses particularly on the elderly who
      are in this situation, but the decision-making process is similar in younger
      patients with ICDs who are in the final phase of their life. 

PMID- 24119394
TI  - [Atrial fibrillation in clinical practice: more answers are required, but do we
      interpret properly the current evidence?].

PMID- 24119395
TI  - [A 76-year-old man with ascites and constitutional syndrome].

PMID- 24119396
TI  - Characterization of glue sizing layers in Portuguese wood paintings from the 15th
      and 16th centuries by SEM secondary electron images and MU-FTIR.
AB  - According to treatises on 15th and 16th century paintings, artists dedicated
      particular attention to the sizing layer-consisting mainly of animal glue applied
      onto the wood support before further application of the ground layer. The
      stability of a painting mainly depends on the presence of a very cohesive sizing
      layer. However, the study of these layers has not received special attention from
      researchers. In this article we present a methodology for characterization of the
      sizing layer both chemically, by IR spectroscopy (Fourier transform infrared
      spectroscopy), and morphologically, by scanning electron microscopy (SEM).
      Secondary electron images obtained by SEM allow precise characterization of such
      layers. Painting reconstructions were used as references in development of the
      method to study the sizing layer in real painting samples. Presented herein are
      examples of this study on 15th and 16th century Portuguese paintings,
      particularly on the Triptych of S. Simao, from the Aveiro Museum, and S. Pedro,
      belonging to the Mercy of Tavira.

PMID- 24119397
TI  - Does an emergency visit to the ER make microRNAs stronger during stress?
AB  - In this issue of Molecular Cell, Wu et al. (2013) report the identification of
      GW182-independent microRNA complexes that confer stronger repression upon serum
      starvation; interestingly, these complexes are associated with polyribosomes and
      the endoplasmic reticulum.

PMID- 24119398
TI  - Same same but different: new structural insight into CRISPR-Cas complexes.
AB  - Three papers in this issue of Molecular Cell report on the structure and
      functional activity of type III CRISPR-Cas effector complexes, revealing novel
      and conserved features of the ribonucleoprotein particles that underlie
      prokaryotic genome defense. The new structures suggest that type I and type III
      complexes follow the same architectural principles and are most likely
      descendants of a common ancestor, the differences in RNA and protein sequences
      and structure of individual components notwithstanding. 

PMID- 24119399
TI  - Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering
      of transcript levels.
AB  - The rates of mRNA synthesis and degradation determine cellular mRNA levels and
      can be monitored by comparative dynamic transcriptome analysis (cDTA) that uses
      nonperturbing metabolic RNA labeling. Here we present cDTA data for 46 yeast
      strains lacking genes involved in mRNA degradation and metabolism. In these
      strains, changes in mRNA degradation rates are generally compensated by changes
      in mRNA synthesis rates, resulting in a buffering of mRNA levels. We show that
      buffering of mRNA levels requires the RNA exonuclease Xrn1. The buffering is
      rapidly established when mRNA synthesis is impaired, but is delayed when mRNA
      degradation is impaired, apparently due to Xrn1-dependent transcription repressor
      induction. Cluster analysis of the data defines the general mRNA degradation
      machinery, reveals different substrate preferences for the two mRNA deadenylase
      complexes Ccr4-Not and Pan2-Pan3, and unveils an interwoven cellular mRNA
      surveillance network.

PMID- 24119400
TI  - Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination
      intermediates.
AB  - Homology-dependent repair of double-strand breaks (DSBs) from nonsister templates
      has the potential to generate loss of heterozygosity or genome rearrangements.
      Here we show that the Saccharomyces cerevisiae Mph1 helicase prevents crossovers
      between ectopic sequences by removing substrates for Mus81-Mms4 or Rad1-Rad10
      cleavage. A role for Yen1 is only apparent in the absence of Mus81. Cells lacking
      Mph1 and the three nucleases are highly defective in the repair of a single DSB,
      suggesting that the recombination intermediates that accumulate cannot be
      processed by the Sgs1-Top3-Rmi1 complex (STR). Consistent with this hypothesis,
      ectopic joint molecules (JMs) accumulate transiently in the mph1Delta mutant and
      persistently when Mus81 is eliminated. Furthermore, the ectopic JMs formed in the
      mus81Delta mutant contain a single Holliday junction (HJ) explaining why STR is
      unable to process them. We suggest that Mph1 and Mus81-Mms4 recognize an early
      strand exchange intermediate and direct repair to noncrossover or crossover
      outcomes, respectively. 

PMID- 24119401
TI  - Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the
      decision to enter the cell cycle.
AB  - Mammalian cells have a remarkable capacity to compensate for heterozygous gene
      loss or extra gene copies. One exception is Down syndrome (DS), where a third
      copy of chromosome 21 mediates neurogenesis defects and lowers the frequency of
      solid tumors. Here we combine live-cell imaging and single-cell analysis to show
      that increased dosage of chromosome 21-localized Dyrk1a steeply increases G1 cell
      cycle duration through direct phosphorylation and degradation of cyclin D1
      (CycD1). DS-derived fibroblasts showed analogous cell cycle changes that were
      reversed by Dyrk1a inhibition. Furthermore, reducing Dyrk1a activity increased
      CycD1 expression to force a bifurcation, with one subpopulation of cells
      accelerating proliferation and the other arresting proliferation by costabilizing
      CycD1 and the CDK inhibitor p21. Thus, dosage of Dyrk1a repositions cells within
      a p21-CycD1 signaling map, directing each cell to either proliferate or to follow
      two distinct cell cycle exit pathways characterized by high or low CycD1 and p21
      levels.

PMID- 24119402
TI  - Structure of the CRISPR interference complex CSM reveals key similarities with
      cascade.
AB  - The Clustered Regularly Interspaced Palindromic Repeats (CRISPR) system is an
      adaptive immune system in prokaryotes. Interference complexes encoded by CRISPR
      associated (cas) genes utilize small RNAs for homology-directed detection and
      subsequent degradation of invading genetic elements, and they have been
      classified into three main types (I-III). Type III complexes share the Cas10
      subunit but are subclassifed as type IIIA (CSM) and type IIIB (CMR), depending on
      their specificity for DNA or RNA targets, respectively. The role of CSM in
      limiting the spread of conjugative plasmids in Staphylococcus epidermidis was
      first described in 2008. Here, we report a detailed investigation of the
      composition and structure of the CSM complex from the archaeon Sulfolobus
      solfataricus, using a combination of electron microscopy, mass spectrometry, and
      deep sequencing. This reveals a three-dimensional model for the CSM complex that
      includes a helical component strikingly reminiscent of the backbone structure of
      the type I (Cascade) family.

PMID- 24119403
TI  - Structure and activity of the RNA-targeting Type III-B CRISPR-Cas complex of
      Thermus thermophilus.
AB  - The CRISPR-Cas system is a prokaryotic host defense system against genetic
      elements. The Type III-B CRISPR-Cas system of the bacterium Thermus thermophilus,
      the TtCmr complex, is composed of six different protein subunits (Cmr1-6) and one
      crRNA with a stoichiometry of Cmr112131445361:crRNA1. The TtCmr complex
      copurifies with crRNA species of 40 and 46 nt, originating from a distinct subset
      of CRISPR loci and spacers. The TtCmr complex cleaves the target RNA at multiple
      sites with 6 nt intervals via a 5' ruler mechanism. Electron microscopy revealed
      that the structure of TtCmr resembles a "sea worm" and is composed of a Cmr2-3
      heterodimer "tail," a helical backbone of Cmr4 subunits capped by Cmr5 subunits,
      and a curled "head" containing Cmr1 and Cmr6. Despite having a backbone of only
      four Cmr4 subunits and being both longer and narrower, the overall architecture
      of TtCmr resembles that of Type I Cascade complexes. 

PMID- 24119405
TI  - An exo-1,3-beta-glucanase GLU1 contributes to the virulence of the wheat tan spot
      pathogen Pyrenophora tritici-repentis.
AB  - Tan spot, caused by Pyrenophora tritici-repentis, is an important foliar disease
      of wheat. In the present study, a gene named glucanase gene (GLU1) encoding a
      putative exo-1,3-beta-glucanase was cloned from a race five isolate of P. tritici
      repentis. Transcription profile analysis of the GLU1 gene showed a carbon source
      control of the accumulation of transcript, which is strongly induced in minimal
      medium but depressed in rich medium. A time-course study of the infection process
      of the wild-type isolate on a susceptible wheat genotype revealed that the
      transcript level of GLU1 increased more than 8000-fold 8 h after inoculation. To
      study its potential function in pathogenicity, GLU1 was silenced via a sense and
      antisense mediated silencing mechanism. One transformant named C1 showed
      significantly reduced growth and sporulation relative to the wild-type.
      Cytological analysis of the infection revealed that C1 produced significantly
      lower numbers of germ tubes and appressoria than the wild-type strain on
      susceptible wheat leaves. This strain, as well as another two transformants,
      caused significantly less disease symptoms relative to the wild-type after
      inoculation onto a susceptible wheat genotype. These results indicate that GLU1
      contributes to the development and virulence of P. tritici-repentis. 

PMID- 24119404
TI  - Structure of an RNA silencing complex of the CRISPR-Cas immune system.
AB  - Bacterial and archaeal clustered regularly interspaced short palindromic repeat
      (CRISPR) loci capture virus and plasmid sequences and use them to recognize and
      eliminate these invaders. CRISPR RNAs (crRNAs) containing the acquired sequences
      are incorporated into effector complexes that destroy matching invader nucleic
      acids. The multicomponent Cmr effector complex cleaves RNA targets complementary
      to the crRNAs. Here, we report cryoelectron microscopy reconstruction of a
      functional Cmr complex bound with a target RNA at ~12 A. Pairs of the Cmr4 and
      Cmr5 proteins form a helical core that is asymmetrically capped on each end by
      distinct pairs of the four remaining subunits: Cmr2 and Cmr3 at the conserved 5'
      crRNA tag sequence and Cmr1 and Cmr6 near the 3' end of the crRNA. The shape and
      organization of the RNA-targeting Cmr complex is strikingly similar to the DNA
      targeting Cascade complex. Our results reveal a remarkably conserved architecture
      among very distantly related CRISPR-Cas complexes.

PMID- 24119406
TI  - The diversity of oomycetes on crayfish: morphological vs. molecular
      identification of cultures obtained while isolating the crayfish plague pathogen.
AB  - Numerous oomycetes colonise the crayfish cuticle, the best known being the
      crayfish plague pathogen Aphanomyces astaci. Although other oomycetes associated
      with crayfish complicate the isolation and molecular detection of A. astaci,
      their diversity is little known. To improve this knowledge, we analysed 95
      oomycete isolates obtained during attempts to isolate A. astaci from crayfish
      presumably infected by this pathogen. We characterized the isolates
      morphologically and by sequencing of the nuclear internal transcribed spacer
      (ITS) region. We identified 13 taxa by molecular analysis. Ten of them were
      assigned to five genera; the remaining three were affiliated with the order
      Saprolegniales but could not be reliably assigned to any genus. Morphological
      identification to species level was only possible for 15 % of isolates; all
      corresponded to Saprolegnia ferax, which was confirmed by ITS sequencing. The
      most frequently isolated species were S. ferax and Saprolegnia australis. Only
      seven isolates of A. astaci were obtained, all from one disease outbreak. We show
      that oomycete cultures obtained as by-products of parasite isolation are valuable
      for oomycete diversity studies, but morphological identification may uncover only
      a fraction of their diversity. Further, we show that crayfish may be frequently
      associated with potentially serious parasites of other organisms. 

PMID- 24119407
TI  - Black yeast habitat choices and species spectrum on high altitude creosote
      treated railway ties.
AB  - Polyextremotolerant black yeast-like fungi thrive in moderately hostile
      environments where they are concomitantly subjected to several types of stress,
      such as toxicity, scarce nutrient availability, and high or low temperature
      extremes. Their ability to assimilate alkylbenzenes (toxic environmental
      pollutants) enhances their growth in harsh conditions, including on railway ties.
      Samples were collected using cotton swabs, premoistened with physiological
      saline, from 658 oak and concrete railway ties at six train stations in Turkey at
      altitudes ranging between 1026 and 1427 m. The samples were inoculated on malt
      extract agar supplemented with chloramphenicol, and incubated at 26  degrees C
      for 4 weeks. Twenty-four samples (3.6 %), 17 from oak and 7 from concrete (5.6 %
      vs. 2 %; P = 0.02), tested positive for fungi. Exophiala crusticola was found to
      be the most common species (n = 13), followed by Exophiala phaeomuriformis (n =
      7) and Exophiala heteromorpha (n = 4). These results suggest that hydrocarbons,
      particularly creosote-treated oak woods, support the growth of black yeasts, some
      of which are opportunists in humans. 

PMID- 24119408
TI  - Development and growth of fruit bodies and crops of the button mushroom, Agaricus
      bisporus.
AB  - We studied the appearance of fruit body primordia, the growth of individual fruit
      bodies and the development of the consecutive flushes of the crop. Relative
      growth, measured as cap expansion, was not constant. It started extremely
      rapidly, and slowed down to an exponential rate with diameter doubling of 1.7 d
      until fruit bodies showed maturation by veil breaking. Initially many outgrowing
      primordia were arrested, indicating nutritional competition. After reaching 10 mm
      diameter, no growth arrest occurred; all growing individuals, whether relatively
      large or small, showed an exponential increase of both cap diameter and biomass,
      until veil breaking. Biomass doubled in 0.8 d. Exponential growth indicates the
      absence of competition. Apparently there exist differential nutritional
      requirements for early growth and for later, continuing growth. Flushing was
      studied applying different picking sizes. An ordinary flushing pattern occurred
      at an immature picking size of 8 mm diameter (picking mushrooms once a day with a
      diameter above 8 mm). The smallest picking size yielded the highest number of
      mushrooms picked, confirming the competition and arrested growth of outgrowing
      primordia: competition seems less if outgrowing primordia are removed early. The
      flush duration (i.e. between the first and last picking moments) was not affected
      by picking size. At small picking size, the subsequent flushes were not fully
      separated in time but overlapped. Within 2 d after picking the first individuals
      of the first flush, primordia for the second flush started outgrowth. Our work
      supports the view that the acquisition of nutrients by the mycelium is demand
      rather than supply driven. For formation and early outgrowth of primordia,
      indications were found for an alternation of local and global control, at least
      in the casing layer. All these data combined, we postulate that flushing is the
      consequence of the depletion of some unknown specific nutrition required by
      outgrowing primordia. 

PMID- 24119409
TI  - Splash and grab: biomechanics of peridiole ejection and function of the funicular
      cord in bird's nest fungi.
AB  - The bird's nest fungi (Basidiomycota, Agaricales) package millions of spores into
      peridioles that are splashed from their basidiomata by the impact of raindrops.
      In this study we report new information on the discharge mechanism in Crucibulum
      and Cyathus species revealed with high-speed video. Peridioles were ejected at
      speeds of 1-5 m per second utilizing less than 2 % of the kinetic energy in
      falling raindrops. Raindrops that hit the rim of the basidiome were most
      effective at ejecting peridioles. The mean angle of ejection varied from 67 to 73
      degrees  and the peridioles travelled over an estimated maximum horizontal
      distance of 1 m. Each peridiole carried a cord or funiculus that remained in a
      condensed form during flight. The cord unravelled when its adhesive surface stuck
      to a surrounding obstacle and acted as a brake that quickly reduced the velocity
      of the projectile. In nature, this elaborate mechanism tethers peridioles to
      vegetation in a perfect location for browsing by herbivores. 

PMID- 24119410
TI  - The sister-group relationships of the largest family of lichenized fungi,
      Parmeliaceae (Lecanorales, Ascomycota).
AB  - Parmeliaceae is the largest family of lichen-forming fungi. In spite of its
      importance for fungal diversity, its relationships with other families in
      Lecanorales remain poorly known. To better understand the evolutionary history of
      the diversification of lineages and species richness in Parmeliaceae it is
      important to know the phylogenetic relationships of the closest relatives of the
      family. A recent study based on two molecular loci suggested that either
      Protoparmelia s. str. or a group consisting of Gypsoplaca and Protoparmelia s.
      str. were the possible sister-group candidates of Parmeliaceae, but that study
      could not distinguish between these two alternatives. Here, we used a four-locus
      phylogeny (nuLSU, ITS, RPB1, MCM7) to reveal relationships of Parmeliaceae with
      other potential relatives in Lecanorales. Maximum likelihood and Bayesian
      analyses showed that Protoparmelia is polyphyletic, with Protoparmelia s. str.
      (including Protoparmelia badia and Protoparmelia picea) being most closely
      related to Parmeliaceae s. str., while the Protoparmelia atriseda-group formed
      the sister-group to Miriquidica. Gypsoplaca formed the sister-group to the
      Parmeliaceae s. str. + Protoparmelia s. str. clade. Monophyly of Protoparmelia as
      currently circumscribed, and Gypsoplaca as sister-group to Parmeliaceae s. str.
      were both significantly rejected by alternative hypothesis testing. 

PMID- 24119411
TI  - Genotypic diversity and migration patterns of Phytophthora infestans in the
      Nordic countries.
AB  - In this study we investigated the genotypic diversity and the migration patterns
      of Phytophthora infestans in the Nordic countries. Isolates of P. infestans from
      outbreaks in 43 fields sampled in 2008 were collected using stratified sampling
      with country, field, and disease foci as the different strata. Microsatellites
      were used as markers to determine the genotypic variation in the sampled
      material. The results show a high genotypic variation of P. infestans in the
      Nordic countries with most of the genotypes found only once among the collected
      isolates. The major part of the genotypic variation was observed within the
      fields, with low differentiation between the fields. The observed low association
      of alleles among loci is consistent with frequent sexual reproduction of P.
      infestans in the Nordic countries. Coalescence analyses did not support a single
      common population for the four countries, thus indicating some degree of
      geographic differentiation. The analyses of migration patterns showed differing
      levels of gene flow among the Nordic countries. No correlation between migration
      rates and geographical distance could be seen. This could be explained by
      different degrees of genetic similarity between the pathogen populations in the
      different countries. 

PMID- 24119412
TI  - In-vitro experimental evaluation of skin-to-surface recovery of four bacterial
      species by antibacterial and non-antibacterial medical examination gloves.
AB  - BACKGROUND: The number of bacteria recovered from a stainless steel coupon after
      touching a pigskin substrate with an examination glove coated on its outside with
      polyhexanide (PHMB), as compared to the number of bacteria recovered in the same
      manner with non-coated control gloves was evaluated. METHODS: Suspensions
      containing 1 * 109 colony-forming units of 4 clinically relevant bacterial
      species (Enterococcus faecium ATCC #51559; Escherichia coli ATCC #25922;
      Klebsiella pneumoniae ATCC #4352; and Staphylococcus aureus ATCC #33591) were
      used to contaminate Gamma-irradiated pigskin substrates. Bacterial recoveries
      from the pigskin substrate, stainless steel coupons, and each glove swatch were
      performed. A difference in the bacterial recovery from the stainless steel
      coupons after touching with coated and uncoated control gloves was measured.
      RESULTS: For E. faecium, the coated glove showed a reduction of 4.63 log10 cfu
      recovery, when compared to control gloves. For E. coli, the coated glove showed
      5.48 log10 cfu, for K. pneumoniae 5.03 log10 cfu, and for S. aureus 5.72 log10
      cfu recovery, when compared to the non-coated control glove. CONCLUSION: An in
      vitro experiment designed to mimic cross-contamination of clinically relevant
      bacteria in a simulated healthcare setting following glove contact with a
      contaminated biological surface and cross-transfer to a stainless steel surface
      has demonstrated that an examination glove coated on its outside surface with
      PHMB was able to reduce bacterial recovery from a contaminated surface by > 4
      log10 cfu, compared to a control non-coated examination glove. These elaborated
      results may encourage further clinical investigation on the clinical impact of an
      antibacterial examination glove.

PMID- 24119413
TI  - Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation
      in experimental non-alcoholic fatty liver disease.
AB  - BACKGROUND: Camel milk (CM) is gaining increasing recognition due to its
      beneficial effects in the control and prevention of multiple health problems. The
      current study aimed to investigate the effects of CM on the hepatic biochemical
      and cellular alterations induced by a high-fat, cholesterol-rich diet (HCD),
      specifically, non-alcoholic fatty liver disease (NAFLD). METHODS: Seventy male
      Wistar rats were divided into four groups: the Control (C) Group fed a standard
      diet; the Control + camel milk (CCM) Group fed a standard diet and CM, the
      Cholesterol (Ch) Group fed a HCD with no CM, and the Cholesterol + camel milk
      (ChM) Group fed a HCD and CM. The following parameters were investigated in the
      studied groups; basal, weekly random and final fasting blood glucose levels,
      intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT),
      serum insulin, serum lipids, liver functions, lipid peroxidation products, the
      antioxidant activity of catalase (CAT) and the levels of reduced glutathione
      (GSH). In addition, HOMA-IR as an index of insulin resistance (IR) and the
      histopathology of the hepatic tissue were assessed. RESULTS: The Ch Group
      developed features similar to those of non-alcoholic steatohepatitis (NASH),
      characterized by hepatic steatosis; inflammatory cellular infiltration in liver
      tissue; altered liver functions; and increased total cholesterol, triglycerides,
      low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol,
      atherogenic index (AI), blood glucose, IR, and malondialdehyde (MDA) levels.
      Additionally, feeding the HCD to animals in the Ch Group decreased CAT activity
      and the GSH and high-density lipoprotein (HDL) cholesterol levels. Camel milk
      intake for eight weeks decreased hepatic fat accumulation and inflammatory
      cellular infiltration, preserved liver function, increased the GSH levels and CAT
      activity, decreased the MDA levels, and ameliorated the changes in the lipid
      profile, AI, and IR in animals from the ChM Group. CONCLUSIONS: CM has a unique
      composition that is rich in minerals; vitamins, insulin and insulin-like protein,
      and it increased HDL-cholesterol and ameliorated the biochemical and cellular
      features of NAFLD in rats that received a HCD. The antioxidant effect of CM is a
      likely mechanism for the altered metabolism and absorption of HCD in the presence
      of CM. Regular consumption of CM could provide a natural way to protect against
      NAFLD induced by a high-fat diet.

PMID- 24119414
TI  - A dissection of the effects of ethylene, H2O2 and high irradiance on antioxidants
      and several genes associated with stress and senescence in tobacco leaves.
AB  - Ethylene and hydrogen peroxide are involved in the modulation of stress responses
      in plants, but their interrelation is not well understood. This work was designed
      to find differences between the actions of ethylene and H2O2 on antioxidants and
      senescence markers. Leaves of Nicotiana tabacum were sprayed with H2O2 or with
      ethephon (precursor of ethylene). To find the possible modulation of responses to
      acute abiotic stress, ethephon- and H2O2-sprayed leaves were further subjected to
      high irradiance (HL). The application of H2O2 strongly stimulated ethylene
      synthesis (ACC). Ethylene and H2O2, as single factors, stimulated the trolox
      equivalent antioxidant capacity (TEAC) and the activity of catalase (CAT), in
      contrast to HL alone (stimulation of nonspecific peroxidases and the total
      glutathione pool). However, after combined treatments (ethylene+HL and H2O2+HL),
      the stimulatory action of H2O2 was related to TEAC and CAT activity, while the
      application of ethylene stimulated the total glutathione pool. Hydrogen peroxide
      enhanced the expression of the three CAT genes (Cat1, Cat2 and Cat3), in contrast
      to ethylene (Cat2 and Cat3) and HL (Cat1). In regard to the markers of senescence
      and pathogenesis the most pronounced difference between the actions of ethylene
      and H2O2, as single factors, was related to NPR1, whereas when leaf spraying was
      combined with HL, differences were found at WRKY53 and PR1a. HL reversed the
      stimulatory effects of H2O2/ethylene-driven enhancements of the expression of
      several genes (Cat1, Cat2, NPR1, WRKY53). These results show that multiple
      stressors, as usually encountered by plants in nature, may largely change those
      expression patterns of genes determined in a single factor analysis. Moreover,
      the actions of HL (often considered the internal H2O2 trigger) and of exogenous
      H2O2 on gene expression are clearly different. 

PMID- 24119415
TI  - Light-harvesting complex B7 shifts the irradiance response of photosynthetic
      light-harvesting regulation in leaves of Arabidopsis thaliana.
AB  - The nuclear LHCB7 gene is common in higher plants, encodes a transcript that is
      well expressed in a subset of leaf mesophyll cells, and is associated with a
      protein product that is homologous to pigment-binding components of the
      photosystem (PS) II peripheral antenna complex. We compared the physiological
      properties of wild type and LHCB7-deficient leaves [DNA insertion, Arabidopsis
      thaliana (At) ecotype Columbia] in terms of pigment content, CO2 exchange, in
      vivo transmittance at 810 nm, and chlorophyll fluorescence. The latter two
      techniques are functional indicators for PSI and PSII, respectively. Key features
      of the mutant phenotype were confirmed using antisense technology and a
      hemizygote of two independent AtLHCB7 DNA insertion lines. Growth, leaf pigment
      composition, white light absorptance, and levels of AtLHCB1-6 were not
      significantly different in the mutant compared to wild type. Likewise, neither
      intrinsic PSII light capture efficiency nor partitioning of absorbed radiation to
      PSII was affected by the mutation. The absence of AtLHCB7 is associated with
      lower rates of light-saturated photosynthesis and a diminished irradiance
      threshold for induction of photoprotective non-photochemical quenching. Overall,
      the pattern of change in light utilization parameters and plastoquinol level
      indicated that loss of AtLHCB7 expression led to slower Rubisco turnover
      characterized by pH-dependent balancing of electron transport to reduced carbon
      assimilation capacity (photosynthetic control). No effect of AtLHCB7 genotype on
      xanthophyll de-epoxidation state was detected suggesting that factors in addition
      to lumenal pH influence zeaxanthin accumulation.

PMID- 24119416
TI  - Dosimetric errors during treatment of centrally located lung tumors with
      stereotactic body radiation therapy: Monte Carlo evaluation of tissue
      inhomogeneity corrections.
AB  - Early experience with stereotactic body radiation therapy (SBRT) of centrally
      located lung tumors indicated increased rate of high-grade toxicity in the lungs.
      These clinical results were based on treatment plans that were computed using
      pencil beam-like algorithms and without tissue inhomogeneity corrections. In this
      study, we evaluated the dosimetric errors in plans with and without inhomogeneity
      corrections and with planning target volumes (PTVs) that were within the zone of
      the proximal bronchial tree (BT). For 10 patients, the PTV, lungs, and sections
      of the BT either inside or within 2cm of the PTV were delineated. Two treatment
      plans were generated for each patient using the following dose-calculation
      methods: (1) pencil beam (PB) algorithm without inhomogeneity correction (IC) (PB
      - IC) and (2) PB with inhomogeneity correction (PB + IC). Both plans had
      identical beam geometry but different beam segment shapes and monitor units (MU)
      to achieve similar conformal dose coverage of PTV. To obtain the baseline dose
      distributions, each plan was recalculated using a Monte Carlo (MC) algorithm by
      keeping MUs the same in the respective plans. The median maximum dose to the
      proximal BT and PTV dose coverage in the PB + IC plans were overestimated by 8%
      and 11%, respectively. However, the median maximum dose to the proximal BT and
      PTV dose coverage in PB - IC plans were underestimated by 15% and 9%. Similar
      trends were observed in low-dose regions of the lung within the irradiated
      volume. Our study indicates that dosimetric bias introduced by unit tissue
      density plans cannot be characterized as underestimation or overestimation of
      dose without taking the tumor location into account. This issue should be
      considered when analyzing clinical toxicity data from early lung SBRT trials that
      utilized unit tissue density for dose calculations. 

PMID- 24119417
TI  - Routes of administration of cannabis used for nonmedical purposes and
      associations with patterns of drug use.
AB  - PURPOSE: Little is known regarding cannabis administration routes for nonmedical
      use-that is, its delivery methods (e.g., joints, water pipe, food). Therefore, we
      examined the prevalence rates of different cannabis delivery methods and assessed
      the relationship of the distinct administration routes with problematic drug use.
      Subgroups of cannabis users were also investigated (i.e., "pure" cannabis users,
      previously described as employing a harmless route of administration, and water
      pipe users, previously described as using a harmful route of administration).
      METHODS: As part of the Cohort Study on Substance Use Risk Factors, 1,763
      cannabis users answered questions concerning their drug use (i.e., routes of
      administration, problematic cannabis use, other illicit drug use). Descriptive
      statistics, latent class analysis, correlations and t-tests were assessed.
      RESULTS: The main administration route was "joints with tobacco"; other routes of
      administration had prevalence rates from 23.99% to 38.23%. In addition,
      increasing the number of administration routes was associated with more
      problematic cannabis use, as well as heavier illicit drug use. Water pipes
      without tobacco were especially linked to heavy drug use patterns, whereas "pure"
      cannabis use seemed less harmful. CONCLUSIONS: Our findings highlighted that
      diversification in routes of administration can be associated with heavier
      illicit drug use. This was especially true for water pipe users, whereas "pure"
      cannabis users, who did not mix cannabis with tobacco, were an exception. Indeed,
      these results may be useful for future preventive programs, which may need to
      focus on those who have diversified routes of administration for cannabis.

PMID- 24119418
TI  - The effect of a school-based intervention on sunbed use in Danish pupils at
      continuation schools: a cluster-randomized controlled trial.
AB  - PURPOSE: To examine the effect of an educational intervention on sunbed use and
      intentions and attitudes toward sunbed use in 14- to 18-year-olds at continuation
      schools. METHODS: We randomized 33 continuation schools either to receive the
      educational intervention (n = 16) or to be controls (n = 17). Intervention
      schools received an e-magazine addressing the health risks of sunbed use.
      Information on behavior and intentions and attitudes toward sunbed use was
      gathered through self-administrated questionnaires before the intervention and at
      6 months as a follow-up. The effect of the intervention was examined by
      multilevel linear regression and logistic regression. RESULTS: Sunbed use was
      significantly lower at follow-up among pupils at intervention schools versus
      pupils at control schools (girls: odds ratio .60, 95% confidence interval .42
      .86; Boys: odds ratio .58, 95% confidence interval .35-.96). The intervention had
      no effect on intention to use sunbeds or attitudes toward sunbed use. The
      analyses revealed a significant impact of school on attitudes toward sunbed; the
      intraclass correlation coefficient was estimated to be 6.0% and 7.8% for girls
      and boys, respectively. CONCLUSIONS: The findings from the present study provide
      new evidence of a positive effect of an educational intervention on sunbed use
      among pupils aged 14-18 years at continuation schools.

PMID- 24119419
TI  - Healthcare technologies, quality improvement programs and hospital organizational
      culture in Canadian hospitals.
AB  - BACKGROUND: Healthcare technology and quality improvement programs have been
      identified as a means to influence healthcare costs and healthcare quality in
      Canada. This study seeks to identify whether the ability to implement healthcare
      technology by a hospital was related to usage of quality improvement programs
      within the hospital and whether the culture within a hospital plays a role in the
      adoption of quality improvement programs. METHODS: A cross-sectional study of
      Canadian hospitals was conducted in 2010. The sample consisted of hospital
      administrators that were selected by provincial review boards. The questionnaire
      consisted of 3 sections: 20 healthcare technology items, 16 quality improvement
      program items and 63 culture items. RESULTS: Rasch model analysis revealed that a
      hierarchy existed among the healthcare technologies based upon the difficulty of
      implementation. The results also showed a significant relationship existed
      between the ability to implement healthcare technologies and the number of
      quality improvement programs adopted. In addition, culture within a hospital
      served a mediating role in quality improvement programs adoption. CONCLUSIONS:
      Healthcare technologies each have different levels of difficulty. As a
      consequence, hospitals need to understand their current level of capability
      before selecting a particular technology in order to assess the level of
      resources needed. Further the usage of quality improvement programs is related to
      the ability to implement technology and the culture within a hospital.

PMID- 24119420
TI  - [Arterial bypass iterative thrombosis and cancer: three cases].
AB  - Cancer associated with venous thromboembolic disease has been recognized since
      Trousseau, but a link between cancer and iterative arterial thrombosis is rarely
      described. We report three cases of patients with iterative bypass thrombosis in
      whom cancer was subsequently diagnosed: lung cancer in one patient and
      hepatocarcinoma and bladder cancer in the others. Smoking and hypertension were
      risk factors in both patients. The link between arterial thrombosis and cancer is
      probably multifactorial. In case of iterative arterial bypass thrombosis, the
      search for cancer is as useful as the control of cardiovascular risk factors and
      the search for antiphospholipid syndrome, since patient management can be
      affected. 

PMID- 24119421
TI  - [A specific questionnaire to evaluate therapeutic inertia in hypertensive
      patients: a pilot study].
AB  - BACKGROUND: Therapeutic inertia (TI) is a recent concept still unknown by many
      physicians. In chronic diseases such as hypertension, it is defined as the
      tendency of physicians not to increase or change antihypertensive medications
      when the target blood pressure is not reached. Acting on TI could improve blood
      pressure control in France. METHOD: This was a single-center prospective pilot
      study conducted by hypertension specialist physicians at the University Cardio
      Vascular Center in Lille (France). It was conducted between March and June 2011.
      Data was collected from 161 hypertensive patients (mean age: 61.64+/-11.18 years;
      98 (60.9%) male; 75 secondary prevention patients). Each physician completed a
      questionnaire on therapeutic inertia. TI was defined as a consultation in which
      treatment change was indicated (systolic blood pressure [BP]>=140 and/or
      diastolic BP>=90mmHg in all patients), but did not occur, with absence of an
      adapted justification of this choice. We considered as an adapted justification:
      a white coat effect demonstrated by ambulatory blood pressure monitoring (ABPM)
      or home blood pressure monitoring; scheduled reassessment of the BP by ABPM;
      recent change in antihypertensive treatment (less than 4 weeks); hospitalization
      needed for complete evaluation of secondary causes of hypertension and a more
      detailed assessment of potential target organ damage in patients with grade 1 or
      2 hypertension. Our study aimed to evaluate rates of TI, to identify factors
      associated with TI, and to test the TI questionnaire. RESULTS: Therapeutic
      inertia as defined in this study occurred in 11 consultations (8.3%) of the 133
      hypertensive patients having uncontrolled BP above or equal to 140 and/or 90mmHg.
      Significant factors associated with TI were older age (Z=2.35, P<0.05) and sleep
      apnea syndrome (chi(2)=8.33, P<0.05). The absence of ambulatory blood pressure
      monitoring before the consultation (chi(2)=4.28, 0.1>P>0.05) and the number of
      consultations (Z=1.92, 0.1>P>0.05) exhibited a significant trend to be associated
      with TI. CONCLUSIONS: Although the rate of TI was low in our study conducted in a
      specialized center, a well-accepted definition of therapeutic inertia would be
      useful for further study. The feasibility of using the questionnaire tested with
      this study shows that this measurement tool could help physicians become more
      aware of TI, both in the hospital and primary care setting. Further multicenter
      studies are needed for validation.

PMID- 24119422
TI  - [Cerebral venous thrombosis, a rare complication of mastoiditis in adults].

PMID- 24119423
TI  - Male hypogonadism.
AB  - Male hypogonadism is a clinical syndrome that results from failure to produce
      physiological concentrations of testosterone, normal amounts of sperm, or both.
      Hypogonadism may arise from testicular disease (primary hypogonadism) or
      dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical
      presentations vary dependent on the time of onset of androgen deficiency, whether
      the defect is in testosterone production or spermatogenesis, associated genetic
      factors, or history of androgen therapy. The clinical diagnosis of hypogonadism
      is made on the basis of signs and symptoms consistent with androgen deficiency
      and low morning testosterone concentrations in serum on multiple occasions.
      Several testosterone-replacement therapies are approved for treatment and should
      be selected according to the patient's preference, cost, availability, and
      formulation-specific properties. Contraindications to testosterone-replacement
      therapy include prostate and breast cancers, uncontrolled congestive heart
      failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment
      should be monitored for benefits and adverse effects. 

PMID- 24119424
TI  - The Minamata Convention on Mercury: risk in perspective.

PMID- 24119425
TI  - What factors influence how two languages are coded in one brain: comment on "The
      bilingual brain: flexibility and control in the human cortex" by Buchweitz and
      Prat.

PMID- 24119426
TI  - Influence of early regulatory problems in infants on their development at 12
      months: a longitudinal study in a high-risk sample.
AB  - BACKGROUND: This study examined the extent to which regulatory problems in
      infants at 4 and 6 months influence childhood development at 12 months. The
      second aim of the study was to examine the influence maternal distress has on 4
      month-old children's subsequent development as well as gender differences with
      regard to regulatory problems and development. METHODS: 153 mother-child dyads
      enrolled in the family support research project "Nobody slips through the net"
      constituted the comparison group. These families faced psychosocial risks (e.g.
      poverty, excessive demands on the mother, and mental health disorders of the
      mother, measured with the risk screening instrument Heidelberger Belastungsskala 
      HBS) and maternal stress, determined with the Parental Stress Index (PSI-SF).
      The children's developmental levels and possible early regulatory problems were
      evaluated by means of the Ages and Stages Questionnaires (ASQ) and a German
      questionnaire assessing problems of excessive crying along with sleeping and
      feeding difficulties (SFS). RESULTS: A statistically significant but only low,
      inverse association between excessive crying, whining and sleep problems at 4 and
      6 months and the social development of one-year-olds (accounting for 5% and 8% of
      the variance respectively) was found. Feeding problems had no effect on
      development. Although regulatory problems in infants were accompanied by
      increased maternal stress level, these did not serve as a predictor of the
      child's social development at 12 months. One-year-old girls reached a higher
      level of development in social and fine motor skills. No gender differences were
      found with regard to regulatory problems, nor any moderating effect of gender on
      the relation between regulatory problems and level of development. CONCLUSIONS:
      Our results reinforce existing knowledge pertaining to the transactional
      association between regulatory problems in infants, maternal distress and
      dysfunctionality of mother-child interactions. They also provide evidence of a
      slight but distinct negative influence of crying and sleeping problems on
      children's subsequent social development. Easily accessible support services
      provided by family health visitors (particularly to the so-called "at-risk
      families") are strongly recommended to help prevent the broadening of children's
      early regulatory problems into other areas of behavior.

PMID- 24119427
TI  - Subjective health status and health-related quality of life among women with
      Recurrent Vulvovaginal Candidosis (RVVC) in Europe and the USA.
AB  - BACKGROUND: Recurrent vulvovaginal candidosis (RVVC) is a chronic condition
      causing discomfort and pain. Health status and health-related quality of life
      (HRQoL) in RVVC were never previously described using validated questionnaires.
      The objective of this study is to describe subjective health status and HRQoL and
      estimate health state utilities among women with RVVC. METHODS: A cross-sectional
      online survey was conducted among women who reported having suffered four or more
      yeast infections over the past 12 months, in five European countries (France,
      Germany, Italy, Spain and the UK) and the USA. Index scores were derived from the
      EQ-5D, a questionnaire providing a single index value for health status. The SF
      36 questionnaire was used for HRQoL assessment. Information on disease severity,
      treatment patterns and productivity was also collected. RESULTS: 12,834 members
      of online research panels were contacted. Among them, 620 women with RVVC (5%)
      were selected to complete the full questionnaire. The mean EQ-5D index score was
      0.70 (95% confidence interval: [0.67, 0.72]) and the difference between women
      with a yeast infection at the time of questionnaire completion and other
      respondents was 0.05 (p = 0.47). The EQ-5D index score increased significantly
      with the time since last infection (p < 0.001). 68% of women reported
      depression/anxiety problems during acute episode, and 54% outside episodes,
      compared to less than 20% in general population (p < 0.001). All SF-36 domain
      scores were significantly below general population norms. Mental health domains
      were the most affected. The impact on productivity was estimated at 33 lost work
      hours per year on average, corresponding to estimated costs between ?266/year and
      ?1,130/year depending on the country. CONCLUSIONS: Subjective health status and
      HRQoL during and in between acute inflammatory episodes in women with RVVC are
      significantly worse than in the general population, despite the use of antifungal
      therapy. The average index score in women with RVVC is comparable to other
      diseases such as asthma or COPD and worse than diseases such as headache/migraine
      according to US and UK catalogs of index scores. The survey also revealed a
      significant loss of productivity associated with RVVC.

PMID- 24119428
TI  - Contribution of regional 3D meniscus and cartilage morphometry by MRI to joint
      space width in fixed flexion knee radiography--a between-knee comparison in
      subjects with unilateral joint space narrowing.
AB  - BACKGROUND: Radiographic joint space width (JSW) is considered the reference
      standard for demonstrating structural therapeutic benefits in knee
      osteoarthritis. Our objective was to determine the proportion by which 3D
      (regional) meniscus and cartilage measures explain between-knee differences of
      JSW in the fixed flexion radiographs. METHODS: Segmentation of the medial
      meniscus and tibial and femoral cartilage was performed in double echo steady
      state (DESS) images. Quantitative measures of meniscus size and position,
      femorotibial cartilage thickness, and radiographic JSW (minimum, and fixed
      locations) were compared between both knees of 60 participants of the
      Osteoarthritis Initiative, with strictly unilateral medial joint space narrowing
      (JSN). Statistical analyses (between-knee, within-person comparison) were
      performed using regression analysis. RESULTS: A strong relationship with side
      differences in minimum and a central fixed location JSW was observed for percent
      tibial plateau coverage by the meniscus (r = .59 and .47; p<.01) and central
      femoral cartilage thickness (r = .69 and .75; p<.01); other meniscus and
      cartilage measures displayed lower coefficients. The correlation of central
      femoral cartilage thickness with JSW (but not that of meniscus measures) was
      greater (r = .78 and .85; p<.01) when excluding knees with non-optimal alignment
      between the tibia and X-ray beam. CONCLUSION: 3D measures of meniscus and
      cartilage provide significant, independent information in explaining side
      differences in radiographic JSW in fixed flexion radiographs. Tibial coverage by
      the meniscus and central femoral cartilage explained two thirds of the
      variability in minimum and fixed location JSW. JSW provides a better
      representation of (central) femorotibial cartilage thickness, when optimal
      positioning of the fixed flexion radiographs is achieved.

PMID- 24119429
TI  - Comparison of foetal US and MRI in the characterisation of congenital lung
      anomalies.
AB  - OBJECTIVES: To compare the accuracy of prenatal ultrasonography (US) to magnetic
      resonance imaging (MRI) in the characterisation of congenital lung anomalies, and
      to assess their agreement with final diagnosis. To evaluate the influence of
      additional MRI information on therapeutic management. METHODS: 26 prenatal
      congenital lung anomalies detected consecutively between 2006 and 2012 were
      retrospectively evaluated. Lesions were initially observed at prenatal US and
      further investigated with MRI. Prenatal US and MRI imaging findings, and
      suggested diagnosis were compared with the final diagnosis, obtained from
      autopsies (4), pathological evaluation following surgical resection (15) and
      postnatal imaging studies (7). RESULTS: Postnatal diagnoses included 7 congenital
      pulmonary airway malformations, 8 complex lesions, 7 overinflations, 1
      sequestration, 1 bronchogenic cyst, 1 blastoma and 1 bilateral lymphangioma.
      Suggested prenatal US and MRI diagnosis was correct in 34.6% and 46.2% of
      patients, respectively, mainly isolated lung lesions with typical imaging
      findings. Nonspecific imaging findings at US and MRI studies were observed in
      38.4% of cases. In 42% of the operated anomalies, pathological dissection
      revealed the presence of complex anomalies. MRI changed the US diagnosis, but not
      the further management in 9.7% of the lesions. CONCLUSIONS: Prenatal US and MRI
      showed a high accuracy in the diagnosis of isolated congenital lung lesions with
      typical imaging findings. However, overall characterisation rates were low,
      because of both a high percentage of complex lesions and of lesions with
      nonspecific imaging findings. MRI was better than US in characterising complex
      lesions, but its additional information did not influence therapy decisions.

PMID- 24119431
TI  - Will watching videos make us better surgeons?

PMID- 24119430
TI  - MRI findings of radiation-induced changes in the urethra and periurethral tissues
      after treatment for prostate cancer.
AB  - PURPOSE: To assess radiotherapy (RT)-induced changes in the urethra and
      periurethral tissues after treatment for prostate cancer (PCa). METHODS AND
      MATERIALS: This retrospective study included 108 men (median age, 64 years;
      range, 43-87 years) who received external-beam radiotherapy (EBRT) and/or
      brachytherapy for PCa and underwent endorectal-coil MRI of the prostate within
      180 days before RT and a median of 20 months (range, 2-62 months) after RT. On
      all MRIs, two readers independently measured the urethral length (UL) and graded
      the margin definition (MD) of the urethral wall and the signal intensities (SIs)
      of the urethral wall and pelvic muscles on 4-point scales. RESULTS: The mean
      urethral length decreased significantly from pre- to post-RT MRI (from 15.2 to
      12.6mm and from 14.4 to 12.9 mm for readers 1 and 2, respectively; both p-values
      <0.0001). Brachytherapy resulted in greater urethral shortening than EBRT. After
      RT, SI in the urethral wall increased in 57% (62/108) and 35% (38/108) of
      patients (readers 1 and 2, respectively). The frequency and magnitude of SI
      increase in pelvic muscles depended on muscle location. In the obturator internus
      muscle, SI increased more often after EBRT than after brachytherapy, while in the
      periurethral levator ani muscle SI increased more often after brachytherapy than
      after EBRT. CONCLUSION: After RT for PCa, MRI shows urethral shortening and
      increased SI of the urethral wall and pelvic muscles in substantial percentages
      of patients.

PMID- 24119432
TI  - Laparoscopic surgery for complex Crohn's disease.
AB  - In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown
      to be both feasible and safe, and is associated with improved outcomes in terms
      of postoperative morbidity and length of hospital stay. At this time, it is
      unclear whether the laparoscopic approach can be routinely proposed as a safe
      procedure for patients with complex CD involving localized abscess, fistula or
      recurrent disease. The aim of this systematic literature review was to assess the
      feasibility and safety of laparoscopic surgery for complex or recurrent CD. In
      the current literature, there are nine non-randomized cohort studies, two of
      which were case-matched. The mean rate of conversion to open laparotomy reported
      in these series ranged from 7% to 42%. Morbidity rate and hospital stay following
      laparoscopic resection for complex CD were similar to those for initial resection
      or for non-complex CD. In summary, even though strong evidence is lacking and
      more contributions with larger size are needed, the limited experiences available
      from the literature confirm that the laparoscopic approach for complex CD is both
      feasible and safe in the hands of experienced IBD surgeons with extensive
      expertise in laparoscopic surgery. Further studies are required to confirm these
      results and determine precisely patient selection criteria. 

PMID- 24119433
TI  - Emerging and historical halogenated flame retardants in fish samples from Iberian
      rivers.
AB  - Forty-eight fish samples from the Llobregat, Ebro, Jucar and Guadalquivir river
      basins (Spain), were analyzed for polybrominated diphenyl ethers (PBDEs),
      decabromodiphenyl ethane (DBDPE), hexabromobenzene (HBB), pentabromoethylbenzene
      (PBEB) and halogenated norbornenes (HNs). The most contaminated river basin was
      the Llobregat, followed by the Ebro, Jucar and Guadalquivir for almost every
      analyzed contaminant. Most abundant PBDE congener was BDE-47 (BDL-396 ng/g lw)
      and the most abundant halogenated norbornene was Dechlorane-602 (BQL-174 ng/g
      lw). Fanti was calculated to determine the different
      bioaccumulation/biodegradation of syn-DP and anti-DP. Biota to sediment
      accumulation factor was calculated in order to compare the bioaccumulation
      capacity of emerging flame retardants with that of "classical" PBDEs. It was
      found that bioaccumulation of halogenated norbornenes is lower than that of
      PBDEs. BDE-99, HBB, PBEB and Dechlorane-604 were not detected in any sample.

PMID- 24119434
TI  - Clinical instability of breast cancer markers is reflected in long-term in vitro
      estrogen deprivation studies.
AB  - BACKGROUND: Long-term estrogen deprivation models are widely employed in an in
      vitro setting to recapitulate the hormonal milieu of breast cancer patients
      treated with endocrine therapy. Despite the wealth information we have garnered
      from these models thus far, a comprehensive time-course analysis of the estrogen
      (ER), progesterone (PR), and human epidermal growth factor 2 (HER-2/neu)
      receptors on the gene and protein level, coupled with expression array data is
      currently lacking. We aimed to address this knowledge gap in order to enhance our
      understanding of endocrine therapy resistance in breast cancer patients. METHODS:
      ER positive MCF7 and BT474 breast cancer cells were grown in estrogen depleted
      medium for 10 months with the ER negative MDA-MB-231 cell line employed as
      control. ER, PR and HER-2/neu expression were analysed at defined short and long
      term time points by immunocytochemistry (ICC), and quantitative real-time RT-PCR
      (qRT-PCR). Microarray analysis was performed on representative samples. RESULTS:
      MCF7 cells cultured in estrogen depleted medium displayed decreasing expression
      of ER up to 8 weeks, which was then re-expressed at 10 months. PR was also down
      regulated at early time points and remained so for the duration of the study.
      BT474 cells generally displayed no changes in ER during the first 8 weeks of
      deprivation, however its expression was significantly decreased at 10 months. PR
      expression was also down-regulated early in BT474 samples and was absent at later
      time points. Finally, microarray data revealed that genes and cell processes down
      regulated in both cell lines at 6 weeks overlapped with those down-regulated in
      aromatase inhibitor treated breast cancer patients. CONCLUSIONS: Our data
      demonstrate that expression of ER, PR, and cell metabolic/proliferative processes
      are unstable in response to long-term estrogen deprivation in breast cancer cell
      lines. These results mirror recent clinical findings and again emphasize the
      utility of LTED models in translational research.

PMID- 24119435
TI  - Factors associated with virological failure in a cohort of combination
      antiretroviral therapy-treated patients managed at a tertiary referral centre.
AB  - BACKGROUND: Recent antiretroviral regimens are potent and better tolerated,
      resulting in a low prevalence of treatment failure. It is important to identify
      the drivers of virological failure, so that patients at risk can be identified
      early and prevention strategies implemented. METHODS: We performed a
      retrospective case-control study of HIV-positive patients on antiretroviral
      therapy and managed at The Alfred Hospital during 2010 to evaluate the predictors
      of virological failure. Controls were matched 3:1 to cases by gender, and by
      clinical review in the same week as the diagnosis of virological failure in the
      case. Predictors of virological failure were identified by multivariate
      conditional logistic regression. RESULTS: Thirty-nine patients were identified
      with treatment failure. In the multivariate model, characteristics associated
      with virological failure were missed clinic appointments in 1 year before
      virological failure (odds ratio (OR)=13.1, 95% confidence interval (CI): 2.8
      61.1), multiple previous combined antiretroviral therapy regimens (OR =4.2, 95%
      CI:1.2-15.3), current hepatitis C infection (OR=8.6, 95% CI: 1.9-38.7), older age
      at HIV diagnosis (OR=1.1, 95% CI: 1.0-1.2), younger age at time of virological
      failure (OR=0.9, 95% CI: 0.8 to 1.0), and CD4 cell count at virological failure
      (OR=0.7, 95% CI: 0.5 to 0.9). CONCLUSIONS: Targeted and appropriate adherence
      support should be provided to treatment-experienced patients, particularly those
      who have missed clinical appointments and those with hepatitis C coinfection.
      Further elucidation of the barriers to clinic attendance may optimise linkage and
      retention in care.

PMID- 24119436
TI  - How do young black men having sex with only women differ from those also having
      sex with men?
AB  - In the US, young Black men (YBM) disproportionately acquire sexually
      transmissible infections (STI), including infection with HIV. This secondary
      analysis compared sexual behaviours of YBM (n = 568) not reporting sex with men
      with those of YBM who have sex with men (YBMSM). In the present study YBMSM were
      generally less likely to report engagement in sexual risk behaviours, less likely
      to report incarceration and more likely to ever be tested for HIV. The findings
      suggest that elevated rates of HIV and/or STI among YBMSM may be a product of
      higher prevalence rates in sexual networks. 

PMID- 24119439
TI  - Public health systems analysis--where the River Kabul meets the River Indus.
AB  - In this paper we review two recent paradigmatic shifts and consider how a two-way
      flow in innovation has been critical to the emergence of new thinking and new
      practices. The first area relates to our understanding of the nature of public
      health systems and the shift from a medical paradigm to a more holistic paradigm
      which emphasises the social, economic and environmental origins of ill-health and
      looks to these as key arenas in which to tackle persistent inequalities in
      populations' health experiences. In respect of this paradigmatic shift, it is
      argued, developing countries were in advance of their more developed
      counterparts. Specifically, the Alma Ata Declaration and the Primary Health Care
      Approach which was central to its implementation pre-figured elements of what was
      to be called in developed countries The New Public Health such as the need for
      greater community involvement and recognition of the importance of other sectors
      in determining health outcomes. But this paradigmatic shift added a new
      complexity to our understanding which made the identification of appropriate
      policy responses increasingly difficult. However, a parallel shift was taking
      place in the cognate field of operational research/systems analysis (OR/SA) which
      was adding greatly to our ability to analyse and to identify key points of
      intervention in complex systems. This led to the emergence of new techniques for
      problem structuring which overcame many of the limitations of formal mathematical
      models which characterised the old paradigm. In this paradigmatic shift developed
      countries have led the way, specifically in the new fields of Community
      Operational Research and Operational Research for Development, but only by
      drawing strongly on the experience and philosophies to be found in developing
      countries. 

PMID- 24119438
TI  - Antimicrobial activity of the bioactive components of essential oils from
      Pakistani spices against Salmonella and other multi-drug resistant bacteria.
AB  - BACKGROUND: The main objective of this study was the phytochemical
      characterization of four indigenous essential oils obtained from spices and their
      antibacterial activities against the multidrug resistant clinical and soil
      isolates prevalent in Pakistan, and ATCC reference strains. METHODS: Chemical
      composition of essential oils from four Pakistani spices cumin (Cuminum cyminum),
      cinnamon (Cinnamomum verum), cardamom (Amomum subulatum) and clove (Syzygium
      aromaticum) were analyzed on GC/MS. Their antibacterial activities were
      investigated by minimum inhibitory concentration (MIC) and Thin-Layer
      Chromatography-Bioautographic (TLC-Bioautographic) assays against pathogenic
      strains Salmonella typhi (D1 Vi-positive), Salmonella typhi (G7 Vi-negative),
      Salmonella paratyphi A, Escherichia coli (SS1), Staphylococcus aureus,
      Pseudomonas fluorescens and Bacillus licheniformis (ATCC 14580). The data were
      statistically analyzed by using Analysis of Variance (ANOVA) and Least
      Significant Difference (LSD) method to find out significant relationship of
      essential oils biological activities at p <0.05. RESULTS: Among all the tested
      essential oils, oil from the bark of C. verum showed best antibacterial
      activities against all selected bacterial strains in the MIC assay, especially
      with 2.9 mg/ml concentration against S. typhi G7 Vi-negative and P. fluorescens
      strains. TLC-bioautography confirmed the presence of biologically active anti
      microbial components in all tested essential oils. P. fluorescens was found
      susceptible to C. verum essential oil while E. coli SS1 and S. aureus were
      resistant to C. verum and A. subulatum essential oils, respectively, as
      determined in bioautography assay. The GC/MS analysis revealed that essential
      oils of C. cyminum, C. verum, A. subulatum, and S. aromaticum contain 17.2%
      cuminaldehyde, 4.3% t-cinnamaldehyde, 5.2% eucalyptol and 0.73% eugenol,
      respectively. CONCLUSIONS: Most of the essential oils included in this study
      possessed good antibacterial activities against selected multi drug resistant
      clinical and soil bacterial strains. Cinnamaldehyde was identified as the most
      active antimicrobial component present in the cinnamon essential oil which acted
      as a strong inhibitory agent in MIC assay against the tested bacteria. The
      results indicate that essential oils from Pakistani spices can be pursued against
      multidrug resistant bacteria.

PMID- 24119440
TI  - [HIV/AIDS screening in community pharmacies].

PMID- 24119441
TI  - Environmental impacts of produced water and drilling waste discharges from the
      Norwegian offshore petroleum industry.
AB  - Operational discharges of produced water and drill cuttings from offshore oil and
      gas platforms are a continuous source of contaminants to continental shelf
      ecosystems. This paper reviews recent research on the biological effects of such
      discharges with focus on the Norwegian Continental Shelf. The greatest concern is
      linked to effects of produced water. Alkylphenols (AP) and polyaromatic
      hydrocarbons (PAH) from produced water accumulate in cod and blue mussel caged
      near outlets, but are rapidly metabolized in cod. APs, naphtenic acids, and PAHs
      may disturb reproductive functions, and affect several chemical, biochemical and
      genetic biomarkers. Toxic concentrations seem restricted to <2 km distance. At
      the peak of discharge of oil-contaminated cuttings fauna disturbance was found at
      more than 5 km from some platforms, but is now seldom detected beyond 500 m.
      Water-based cuttings may seriously affect biomarkers in filter feeding bivalves,
      and cause elevated sediment oxygen consumption and mortality in benthic fauna.
      Effects levels occur within 0.5-1 km distance. The stress is mainly physical. The
      risk of widespread, long term impact from the operational discharges on
      populations and the ecosystem is presently considered low, but this cannot be
      verified from the published literature.

PMID- 24119442
TI  - Combined use of chemical, biochemical and physiological variables in mussels for
      the assessment of marine pollution along the N-NW Spanish coast.
AB  - This study undertakes an overall assessment of pollution in a large region (over
      2500 km of coastline) of the N-NW Spanish coast, by combining the use of
      biochemical (AChE, GST, GPx) and physiological (SFG) responses to pollution, with
      chemical analyses in wild mussel populations (Mytilus galloprovincialis). The
      application of chemical analysis and biological techniques identified polluted
      sites and quantified the level of toxicity. High levels of pollutants were found
      in mussel populations located close to major cities and industrialized areas and,
      in general, average concentrations were higher in the Cantabrian than in the
      Iberian Atlantic coast. AChE activities ranged between 5.8 and 27.1 nmol/min/mg
      prot, showing inhibition in 12 sampling sites, according to available
      ecotoxicological criteria. GST activities ranged between 29.5 and 112.7
      nmol/min/mg prot, and extreme variability was observed in GPx, showing activities
      between 2.6 and 64.5 nmol/min/mg prot. Regarding SFG, only 5 sites showed
      'moderate stress' (SFG value below 20 J/g/h), and most sites presented a 'high
      potential growth' (>35 J/g/h) corresponding to a 'healthy state'. Multivariate
      statistical techniques applied to the chemical and biological data identified
      PCBs, organochlorine pesticides and BDEs as the main responsible of the observed
      toxicity. However, the alteration of biological responses caused by pollutants
      seems to be, in general, masked by biological variables, namely age and mussel
      condition, which have an effect on the mussels' response to pollutant exposure. 

PMID- 24119443
TI  - Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer
      patients receiving first-line oxaliplatin-based treatment.
AB  - The conventional first-line chemotherapy for metastatic colorectal cancer (mCRC)
      consists of fluorouracil (5-FU) in combination with either oxaliplatin or
      irinotecan. We have explored microRNAs (miRNAs) in plasma as potential predictive
      markers to oxaliplatin-based chemotherapy. The expression of 742 miRNAs was
      examined in plasma samples from 24 mCRC patients (12 responders and 12 non
      responders) before onset and after four cycles of 5-FU/oxaliplatin. The top
      differentially expressed miRNAs between responders and non-responders were
      selected for further analysis in a validation cohort of 150 patients. In the
      validation cohort, there was a significant overrepresentation of miRNAs with
      higher mean expression in the non-responder group than in the responder group
      before treatment (p < 0.002). Moreover, we found three miRNAs (miR-106a, miR-484,
      and miR-130b) to be significantly differentially expressed before treatment (p =
      0.008, 0.008, and 0.008, respectively). All three miRNAs were upregulated in non
      responders. High expression of miR-27b, miR-148a, and miR-326 were associated
      with decreased progression-free survival (Hazard ratios (HR) of 1.4 (95% CI 1.1
      1.8, p = 0.004), 1.3 (95% CI 1.1-1.6, p = 0.007), and 1.4 (95% CI 1.1-1.8, p =
      0.008), respectively). miR-326 was also associated with decreased overall
      survival (HR 1.5 (95% CI 1.1-2.0, p = 0.003)). There were no significantly
      differentially expressed miRNAs in association with clinical outcome after four
      cycles of chemotherapy. The present study demonstrates that plasma miRNAs
      analyzed before treatment may serve as non-invasive markers predicting outcome in
      mCRC patients treated with 5-FU and oxaliplatin-based chemotherapy. 

PMID- 24119444
TI  - Selective effects of head posture on ocular vestibular-evoked myogenic potential
      (oVEMP) by bone-conducted vibration.
AB  - OBJECTIVE: By altering head postures from sitting, supine to head hanging, this
      study investigated the effects of gravitational force on ocular vestibular-evoked
      myogenic potential (oVEMP) via either air-conducted sound (ACS) or bone-conducted
      vibration (BCV) stimuli. METHODS: Twenty healthy volunteers underwent the oVEMP
      test via ACS or BCV stimuli with the sitting, supine, and head hanging positions
      on the same day in a randomized order. RESULTS: All subjects had clear BCV oVEMPs
      in the three head postures. No significant differences existed in terms of mean
      nI and pI latencies, the nI-pI interval, and asymmetry ratio regardless of
      various positions. However, the mean nI-pI amplitude with the head hanging
      position (15.9 +/- 6.4 MUV) was significantly larger than that with the sitting
      position (13.8 +/- 6.0 MUV), but not significantly larger than that with the
      supine position (14.7 +/- 6.1 MUV). Nevertheless, such a difference in reflex
      amplitude does not exist in oVEMPs elicited by ACS stimuli. With the sitting
      position, mean linear acceleration at the mastoids in response to BCV stimuli was
      -0.06 +/- 0.02, 0.20 +/- 0.04 and -0.04 +/- 0.02 g along the x-, y-, and z-axis,
      respectively, which did not differ significantly from those with the head hanging
      position. CONCLUSION: By altering head postures from sitting to head hanging,
      gravitational force can exert a selective effect on the reflex amplitude of
      oVEMPs elicited by BCV stimuli, but not by ACS stimuli. SIGNIFICANCE: Compared to
      ACS mode, BCV mode can provoke higher response rate, generate earlier and larger
      waveforms, and be influenced by both dynamic shearing force and static
      gravitational force to enlarge the reflex amplitude of oVEMPs.

PMID- 24119445
TI  - Can EEG predict outcomes in genetic generalized epilepsies?

PMID- 24119447
TI  - Mapping out the structural changes of natural and pretreated plant cell wall
      surfaces by atomic force microscopy single molecular recognition imaging.
AB  - BACKGROUND: Enzymatic hydrolysis of lignocellulosic biomass (mainly plant cell
      walls) is a critical process for biofuel production. This process is greatly
      hindered by the natural complexity of plant cell walls and limited accessibility
      of surface cellulose by enzymes. Little is known about the plant cell wall
      structural and molecular level component changes after pretreatments, especially
      on the outer surface. Therefore, a more profound understanding of surface
      cellulose distributions before and after pretreatments at single-molecule level
      is in great need. In this study, we determined the structural changes,
      specifically on crystalline cellulose, of natural, dilute sulfuric acid
      pretreated and delignified cell wall surfaces of poplar, switchgrass, and corn
      stover using single molecular atomic force microscopy (AFM) recognition imaging.
      RESULTS: The AFM tip was first functionalized by a family 3 carbohydrate-binding
      module (CBM3a) (Clostridium thermocellum Scaffoldin) which specifically
      recognizes crystalline cellulose by selectively binding to it. The surface
      structural changes were studied at single molecule level based on the recognition
      area percentage (RAP) of exposed crystalline cellulose over the imaged cell wall
      surface. Our results show that the cell wall surface crystalline cellulose
      coverage increased from 17-20% to 18-40% after dilute acid pretreatment at 135
      degrees C under different acid concentrations and reached to 40-70% after
      delignification. Pretreated with 0.5% sulfuric acid, the crystalline cellulose
      surface distributions of 23% on poplar, 28% on switchgrass and, 38% on corn
      stover were determined as an optimized result. Corn stover cell walls also show
      less recalcitrance due to more effective pretreatments and delignification
      compared to poplar and switchgrass. CONCLUSIONS: The dilute acid pretreatment can
      effectively increase the cellulose accessibility on plant cell wall surfaces. The
      optimal acid concentration was determined to be 0.5% acid at 135 degrees C,
      especially for corn stover. This study provides a better understanding of surface
      structural changes after pretreatment such as lignin relocation, re
      precipitation, and crystalline cellulose distribution, and can lead to potential
      improvements of biomass pretreatment.

PMID- 24119446
TI  - What does complement do in Alzheimer's disease? Old molecules with new insights.
AB  - Increasing evidence suggests that inflammatory and immune components in brain are
      important in Alzheimer's disease (AD) and anti-inflammatory and immunotherapeutic
      approaches may be amenable to AD treatment. It is known that complement
      activation occurs in the brain of patients with AD, and contributes to a local
      inflammatory state development which is correlated with cognitive impairment. In
      addition to the complement's critical role in the innate immune system
      recognizing and killing, or targeting for destruction, complement proteins can
      also interact with cell surface receptors to promote a local inflammatory
      response and contributes to the protection and healing of the host. On the other
      hand, complement activation also causes inflammation and cell damage as an
      essential immune function to eliminate cell debris and potentially toxic protein
      aggregates. It is the balance of these seemingly competing events that influences
      the ultimate state of neuronal function. Our mini review will be focusing on the
      unique molecular interactions happening in the AD development, the functional
      outcomes of those interactions, as well as the contribution of each element to
      AD. 

PMID- 24119448
TI  - Design, synthesis and biological evaluation of N2,N4-disubstituted-1,1,3-trioxo
      2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives as HIV-1 NNRTIs.
AB  - A series of N2,N4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2
      b][1,2,4,6]thiatriazine derivatives (PTTDs) was designed and synthesized by a
      facile route. The biological assay results showed that five most potent compounds
      displayed inhibitory activity against HIV-1 at low micromolar concentrations
      (EC50=5.1-8.9 MUM). Structure-activity relationship analysis indicated that N2-(3
      halogenated-benzyl) analogues were more potent than N2-(unsubstituted-benzyl)
      analogues. The N4-substitutions contributed to the antiviral activity in the
      following order: 2-/3-cyano substituted benzyl > 2-/3-halogenated benzyl > non
      substituted benzyl > 4-halogenated benzyl. Docking studies of the representative
      compound revealed the binding conformation of these compounds and provided
      critical insights for the further development of PTTD analogues.

PMID- 24119449
TI  - CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies.
AB  - Despite almost 30 years since the identification of the human immunodeficiency
      virus type I (HIV-1), development of effective AIDS vaccines has been hindered by
      the high mutability of HIV-1. The HIV-1 co-receptors CCR5 and CXCR4 are
      genetically stable, but viral proteins may mutate rapidly during the course of
      infection. CXCR4 is a seven transmembrane G protein-coupled receptor, possessing
      an N-terminal region (NT) and three extracellular loops (ECL1-3). Previous
      studies have shown that the CXCR4-ED-derived peptides inhibit the entry of HIV-1
      by interacting with gp120, an HIV-1 envelope glycoprotein. In the present study,
      antigenicity of CXCR4-derived peptides has been investigated and the anti-HIV-1
      effects of induced antisera have been assessed. It was found that CXCR4-ED
      derived antigen molecules immunize mice, showing that the linear peptides have
      higher antigenicity than the cyclic peptides. The L1- and L2-induced antisera
      inhibited the HIV-1 entry significantly, while anti-N1 antibodies have no
      inhibitory activity. This study produced promising examples for the design of
      AIDS vaccines which target the human protein and can overcome mutability of HIV
      1.

PMID- 24119450
TI  - Serosurvey of Schmallenberg Virus Infections in Sheep and Goat Flocks in Lower
      Saxony, Germany.
AB  - Schmallenberg virus (SBV) infections can cause congenital musculoskeletal and
      vertebral malformations as well as neurological failures in foetuses of several
      ruminant species if susceptible mother animals were infected during early
      gestation. Blood samples gained from 17 goat and 64 sheep flocks in Lower Saxony
      (LS), Germany (January-May 2012), which is located in the core region of the
      2011/2012 epidemic were tested for antibodies against SBV by ELISA to detect past
      exposure to SBV. A SBV-specific questionnaire was raised in all flocks. The
      calculated median within-herd prevalence was 43.8% (min-max: 5.6-93.3%) for goats
      and 58.7% (min-max: 6.5-100%) for sheep, showing that small ruminants in LS,
      especially goats, are still at risk of novel SBV infections in the following
      lambing seasons as not all animals have seroconverted yet. Statistical analysis
      revealed that goats have a significantly lower risk of SBV infections than sheep
      which might be explained by different host preferences of Culicoides ssp. as main
      vectors for SBV and different housing conditions.

PMID- 24119451
TI  - Risk of intracranial injury after minor head trauma in patients with pre-injury
      use of clopidogrel.
AB  - BACKGROUND: Clopidogrel is an adenosine diphosphate receptor antagonist. The risk
      of intracranial hemorrhage following minor head trauma in patients with pre
      injury use of clopidogrel has not been fully determined. METHODS: This case
      controlled study examined the effects of pre-injury use of clopidogrel in adult
      (age 14 years and older) patients with minor head trauma. RESULTS: During the
      study period, 1660 patients head computed tomography scans were performed in the
      emergency department, of which 658 met inclusion criteria. Intracranial
      hemorrhage was noted in 30% of patients on clopidogrel, compared with 2.2% of
      those patients without pre-injury use of clopidogrel. After performing a logistic
      regression analysis for confounders, the pre-injury use of clopidogrel was
      significantly associated with intracranial hemorrhage in this study population
      (OR 16.7; 95% CI 1.71-162.7). CONCLUSION: The use of clopidogrel is associated
      with a significantly increased risk of developing intracranial hemorrhage
      following minor trauma.

PMID- 24119452
TI  - [Diagnostic use of macular layer analysis by SD-OCT in primary open angle
      glaucoma].
AB  - PURPOSE: The purpose of this study is to evaluate the diagnostic ability of
      segmentation of the various internal macular layers by spectral domain optical
      coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec (CZM), Dublin, CA, USA)
      and to compare it to that of the peripapillary retinal nerve fiber layer (cpRNFL)
      in primary open angle glaucoma (POAG). MATERIALS AND METHODS: This study included
      252 eyes diagnosed with primary open angle glaucoma (POAG) (164 early POAG, 44
      moderate POAG and 44 advanced POAG) and 223 eyes of control subjects. All
      patients underwent visual field testing (Humphrey Field Analyser, SITA-Standard
      24-2, CZM), and SD-OCT imaging (Cirrus HD-OCT) of the macular and optic nerve
      head regions (ganglion cell analysis (GCA), macular cube 200*200; optic disc cube
      200*200). OCT macular scans were segmented into macular nerve fiber layer (mNFL),
      ganglion cell layer with inner plexiform layer (GCIPL), outer retinal layers, and
      ganglion cell complex (GCC) (mNFL+GCIPL). Glaucoma discriminating ability was
      assessed using the area under the receiver operator characteristic curve (AUC)
      for all macular parameters and mean circumpapillary retinal nerve fibre layer
      (cpRNFL). RESULTS: For the entire POAG population of this study, the minimum
      GCIPL index provided greater diagnostic ability than the other parameters
      studied, with a statistically significant difference in their AUC (minimum GCIPL
      [0.887], mean GCIPL [0.865], GCC [0.863], cpRNFL [0.823], mean mNFL [0.786] and
      minimum mNFL [0.742]). The results were similar in the early POAG group but
      without any statistically significant difference with the cpRNFL parameter. In
      the moderate POAG group, the diagnostic ability was similar for all indices,
      whereas in the advanced POAG group, minimum GCIPL and GCC gave the largest AUC
      indices. DISCUSSION AND CONCLUSION: The minimum macular GCIPL is a new index
      obtained with the GCA algorithm of the Cirrus HD-OCT. It appears to have an
      excellent ability to detect glaucoma at every stage and demonstrates performance
      comparable to that of the cpRNFL parameter, in combination with which it may
      provide important complementary information for clinical practice.

PMID- 24119453
TI  - Orbital cysticercosis and third nerve palsy. Reply.

PMID- 24119454
TI  - [Management of orbital cavernous hemangioma - evaluation of surgical approaches:
      report of 43 cases].
AB  - Cavernous hemangioma is the most frequent benign orbital tumor in adults. The
      purpose of this study was to examine its clinical features, to define surgical
      indications, and to determine the roles of the various surgical approaches
      praticed in ophthalmology: transconjunctival (increasingly utilized), anterior
      transcutaneous, and lateral orbitotomy. The records of all patients treated for
      orbital cavernous hemangioma (OCH) since 2004 at the Fondation Rothschild (Paris,
      France) were retrospectively reviewed. Forty-three patients were treated for
      orbital cavernous hemangioma. Fifty-eight percent were women, mean age 50.2; 79 %
      of the tumors were intraconal. Among those patients, 36 underwent surgical
      removal, 5 were followed periodically, and 2 were lost to follow-up. The main
      surgical indications were: optic nerve compression (26 patients), proptosis (24
      patients) and diplopia (3 patients). Transconjunctival, anterior transcutaneous
      and Kronlein approaches were used in 16, 12 and 4 patients respectively. Four
      patients had intrapalpebral hemangiomas easily reached transcutaneously. Two
      patients demonstrated transient partial 3rd nerve palsy (one with the lateral
      orbitotomy approach and one with the transconjunctival approach), one patient
      with the lateral orbitotomy approach developed a palsy of the superior branch of
      the 3rd nerve, and one patient with the transcutaneous anterior approach
      developed mydriasis. Surgical excision of OCH's is required in the presence of
      clinical complications. The transconjunctival approach is a safe technique which
      can lead to complete resection of the tumor in most cases.

PMID- 24119455
TI  - Expression profiles of angiogenesis-related proteins in prevascular three
      dimensional tissues using cell-sheet engineering.
AB  - The prefabrication of endothelial cell network assembly (ECNA) in tissue-engineer
      multi-layered cell-sheets, known as in vitro prevascularization, is beneficial
      strategy for inducing anastomosis with the host vasculature after
      transplantation. However, the mechanisms of neovascularization via transplanted
      prevascular cell-sheets are unknown. This study investigated neovascularization
      process and angiogenesis-related protein secretion by prevascular cell-sheets.
      Prevascular (ECNA-positive) double-layered fibroblast (FB) sheets were created by
      sandwiching human aortic endothelial cells (HAECs) between two human dermal FB
      sheets. As the ECNA-negative control, FBs-sandwiching double-layered FB sheets
      were used. Two types of cell-sheets were subcutaneously transplanted into immune
      deficient rats. At 3 days after transplantation, induction of the newly-formed
      microvessels near the host vasculature was observed in the ECNA-positive cell
      sheet. In contrast, no neovessel was observed in the ECNA-negative cell-sheet at
      1 week after transplantation. Consequently, the secretion of angiogenesis-related
      proteins in conditioned media of each cell-sheet cultured for 3 days were
      compared. The levels of hepatocyte growth factor (HGF), placenta growth factor
      (PlGF) and matrix metalloproteinase-9 (MMP-9) significantly increased in the ECNA
      positive cell-sheets. These results suggested that these molecules might involve
      in neovascularization after the transplantation of prevascular cell-sheets. These
      findings may contribute to understanding its mechanism. 

PMID- 24119456
TI  - Epicardial delivery of collagen patches with adipose-derived stem cells in rat
      and minipig models of chronic myocardial infarction.
AB  - Although transplantation of adipose-derived stem cells (ADSC) in chronic
      myocardial infarction (MI) models is associated with functional improvement, its
      therapeutic value is limited due to poor long-term cell engraftment and survival.
      Thus, the objective of this study was to examine whether transplantation of
      collagen patches seeded with ADSC could enhance cell engraftment and improve
      cardiac function in models of chronic MI. With that purpose, chronically
      infarcted Sprague-Dawley rats (n = 58) were divided into four groups and
      transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat
      ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function
      were assessed 4 months after transplantation. In addition, Gottingen minipigs (n
      = 18) were subjected to MI and then transplanted 2 months later with CS or CS
      seeded with autologous minipig ADSC (CS-pADSC). Functional and histological
      assessments were performed 3 months post-transplantation. Transplantation of CS
      rADSC was associated with increased cell engraftment, significant improvement in
      cardiac function, myocardial remodeling, and revascularization. Moreover,
      transplantation of CS-pADSC in the pre-clinical swine model improved cardiac
      function and was associated with decreased fibrosis and increased vasculogenesis.
      In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and
      was associated with a significant improvement in cardiac function and myocardial
      remodeling.

PMID- 24119458
TI  - Association of body mass index and smoking on outcome of Chinese patients with
      colorectal cancer.
AB  - BACKGROUND: The impact of body mass index (BMI) on the prognosis of patients with
      colorectal cancer remains largely unknown, particularly in Asian populations.
      Therefore, the aim of this study was to examine the influence of BMI on
      clinicopathological characteristics and mortality of Chinese colorectal cancer
      patients. METHODS: The study cohort consisted of 525 patients who were diagnosed
      with colorectal cancer and underwent radical surgery at the second hospital of
      Harbin Medical University between June 2004 and August 2011. Study participants
      were divided into two BMI categories: normal weight (BMI <23 kg/m2) and
      overweight (BMI >=23 kg/m2). RESULTS: Of 525 patients, 208 patients (39.6%) were
      included in the normal-weight group and 317 patients were included in the
      overweight group. During the mean follow-up period of 48.8 months, 89 patients
      had disease recurrence and 131 deaths occurred. High BMI was significantly
      correlated with younger age, presence of diabetes, alcohol consumption, distal
      colon tumors, amount of lymph node harvested and pathological stage. No
      statistically significant correlation was found between high BMI and progression
      free survival (PFS) or overall survival (OS) when the total group of patients was
      considered (P = 0.077 and P = 0.701, respectively). Cigarette-smoking patients
      had significantly shorter OS than patients who had never smoked (hazard ratio =
      1.613, 95% confidence interval = 1.133 to 2.296; P = 0.008), and this difference
      in OS remained significant in multivariate analysis. Cigarette-smoking patients
      did not have significantly different PFS compared with patients who had never
      smoked. CONCLUSION: There was no significant correlation between obesity and
      outcomes of patients with colorectal cancer. In addition, our findings support
      the claims that cigarette smoking may be partially responsible for the divergent
      mortality of patients with colorectal cancer.

PMID- 24119457
TI  - Nerve regeneration and elastin formation within poly(glycerol sebacate)-based
      synthetic arterial grafts one-year post-implantation in a rat model.
AB  - The objective of this study was to evaluate the long-term performance of cell
      free vascular grafts made from a fast-degrading elastic polymer. We fabricated
      small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS)
      reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts
      were interpositioned in rat abdominal aortas and characterized at 1 year post
      implant. Grafts remodeled into "neoarteries" (regenerated arteries) with similar
      gross appearance to native rat aortas. Neoarteries mimic arterial tissue
      architecture with a confluent endothelium and media and adventita-like layers.
      Patent vessels (80%) showed no significant stenosis, dilation, or calcification.
      Neoarteries contain nerves and have the same amount of mature elastin as native
      arteries. Despite some differences in matrix organization, regenerated arteries
      had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries
      responded to vasomotor agents, albeit with different magnitude than native
      aortas. These data suggest that an elastic vascular graft that resorbs quickly
      has potential to improve the performance of vascular grafts used in small
      arteries. This design may also promote constructive remodeling in other soft
      tissues.

PMID- 24119459
TI  - Specific RNA-protein interactions in the replication of foamy viruses (FVs).
AB  - The FV pathway of replication is fundamentally different from what we know about
      the strategy employed by all known other retroviruses. This unique pathway
      involves some distinctive RNA-protein interactions, which range from nuclear RNA
      export to activation of reverse transcription late in the viral replication
      cycle. Some peculiarities of this replication strategy will be summarized here. 

PMID- 24119460
TI  - Chemical exchange saturation transfer MR imaging of articular cartilage
      glycosaminoglycans at 3 T: Accuracy of B0 Field Inhomogeneity corrections with
      gradient echo method.
AB  - Glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) is an important
      molecular MRI methodology developed to assess changes in cartilage GAG
      concentrations. The correction for B0 field inhomogeneity is technically crucial
      in gagCEST imaging. This study evaluates the accuracy of the B0 estimation
      determined by the dual gradient echo method and the effect on gagCEST
      measurements. The results were compared with those from the commonly used z
      spectrum method. Eleven knee patients and three healthy volunteers were scanned.
      Dual gradient echo B0 maps with different ?TE values (1, 2, 4, 8, and 10 ms) were
      acquired. The asymmetry of the magnetization transfer ratio at 1 ppm offset
      referred to the bulk water frequency, MTRasym(1 ppm), was used to quantify
      cartilage GAG levels. The B0 shifts for all knee patients using the z-spectrum
      and dual gradient echo methods are strongly correlated for all ?TE values used (r
      = 0.997 to 0.786, corresponding to ?TE = 10 to 1 ms). The corrected MTRasym(1
      ppm) values using the z-spectrum method (1.34% +/- 0.74%) highly agree only with
      those using the dual gradient echo methods with ?TE = 10 ms (1.72% +/- 0.80%; r =
      0.924) and 8 ms (1.50% +/- 0.82%; r = 0.712). The dual gradient echo method with
      longer ?TE values (more than 8 ms) has an excellent correlation with the z
      spectrum method for gagCEST imaging at 3T.

PMID- 24119461
TI  - One-step nucleic acid amplification assay also predicts axillary lymph node
      status in breast cancer patients: further molecular diagnostic evidence.

PMID- 24119462
TI  - Is carpal tunnel syndrome a slow, chronic, progressive nerve entrapment?
AB  - OBJECTIVE: The aim of this study is to investigate the presenting profile of
      patients with carpal tunnel syndrome (CTS) at various ages. METHODS: We performed
      a cross-sectional study of CTS, analysing the correlation between severity and
      age. RESULTS: We examined 3108 subjects with CTS, whose frequency increased from
      20.9% for the age group 20-29 years to 61.7% for the age group 50-59 years. It
      remained at almost 50% in people aged over 80 years (49.2%). More than 50% of
      people younger than 30 years had mild CTS. Severe CTS progressively increased,
      reaching more than 50% of the CTS diagnoses in people over 80 years. Of the total
      number of cases, 80.8% of subjects had bilateral CTS. Mild NCS-EMG abnormalities
      were seen in 74.1% of patients with unilateral involvement, whereas moderate and
      severe CTS appeared in 70.3% of patients with bilateral involvement. CONCLUSION:
      There was a clear trend of deterioration with advancing years when comparing
      severity to age. SIGNIFICANCE: CTS seems to be a chronic condition whose signs
      and symptoms may vary and progress, becoming worse over time.

PMID- 24119463
TI  - Identifying youth at risk for psychosis using the Behavior Assessment System for
      Children, Second Edition.
AB  - Identification of youth at risk for or with early psychosis has become the focus
      of many research and clinical initiatives, as early intervention may be linked to
      better long-term outcomes. Efforts to facilitate identification have led to the
      development of several self-report instruments that intend to quickly assess
      "attenuated" psychosis, potentially screening people for further evaluation. The
      widely used Behavior Assessment System for Children, Second Edition (BASC-2)
      includes the atypicality scale, a scale that may be useful for risk screening as
      it is designed to recognize emerging symptoms of psychosis. The current study
      aimed to evaluate the utility of the BASC-2 for identifying youth at high
      clinical risk or with early psychosis within a sample of 70 help-seeking
      participants aged 12-22. Atypicality scores were compared to risk status (low
      risk, high-risk or early psychosis) as determined by the clinician-administered
      Structured Interview for Psychosis-Risk Syndromes (SIPS). The relative accuracy
      of the atypicality scale was evaluated against three self-report screeners
      specifically designed to identify this population. Results indicate that the BASC
      2 atypicality scale may be a useful tool for identifying youth in early stages of
      psychosis. Moreover, the atypicality scale is comparable if not superior to other
      specialized risk screening instruments in terms of predictive ability. Given the
      widespread use of the BASC-2 across educational and mental health settings,
      evidence for convergent validity between the BASC-2 atypicality scale and SIPS
      diagnoses has the potential to make screening available to a greater population
      and facilitate earlier detection and intervention. 

PMID- 24119465
TI  - Limited utility of surveillance imaging for detecting disease relapse in patients
      with non-Hodgkin lymphoma in first complete remission.
AB  - INTRODUCTION: Surveillance imaging with computed tomography (CT) or positron
      emission tomography with CT (PET/CT) is commonly used in practice in patients
      with non-Hodgkin lymphoma (NHL) who are in remission after front-line therapies.
      We aimed to determine the utility of routine imaging for detecting first relapse
      in patients with NHL in complete remission (CR) after first-line therapies.
      PATIENTS AND METHODS: We retrospectively analyzed patients with NHL who achieved
      CR after first-line therapies and then subsequently had disease relapse. We
      evaluated whether the relapse was detected solely by surveillance CT or PET/CT or
      by patient-reported symptoms or physical examination findings, or both. Subgroup
      analysis was performed on baseline histologic type (indolent vs. aggressive NHL).
      Data were also collected to determine the cost of surveillance PET/CT and the
      number of additional diagnostic imaging procedures, invasive procedures, and
      iatrogenic complications directly resulting from an abnormality detected on a
      surveillance scan. RESULTS: One hundred sixty-three patients with first relapse
      of NHL between January 1, 2000 and December 31, 2010 were included. The majority
      of the relapses were detected by patient-reported symptoms or physical
      examination, or both, as opposed to surveillance imaging (77.9% [n = 127] vs.
      22.1% [n = 36]; P < .0001). There was no overall survival difference between the
      2 groups (P = .66). Patient-reported symptoms led to the detection of the
      majority of relapses in aggressive (85.7% [n = 72] vs. 14.3% [n = 12]; P < .0001)
      as well as indolent NHL (69.6% [n = 55] vs. 30.4% [n = 24]; P = .0007).
      Surveillance PET/CT contributed to more than 75% of follow-up health care costs
      in the first 2 years of monitoring for relapse. The surveillance imaging group
      had 1 reported case of iatrogenic pneumothorax. CONCLUSION: Our retrospective
      analysis suggests that there is a limited role for surveillance imaging by CT or
      PET/CT in detecting first relapse in NHL. There was no difference in survival
      outcomes between the 2 groups in our study.

PMID- 24119464
TI  - Sequential processing deficits in schizophrenia: relationship to neuropsychology
      and genetics.
AB  - Utilizing a combination of neuropsychological and cognitive neuroscience
      approaches may be essential for characterizing cognitive deficits in
      schizophrenia and eventually assessing cognitive outcomes. This study was
      designed to compare the stability of select exemplars for these approaches and
      their correlations in schizophrenia patients with stable treatment and clinical
      profiles. Reliability estimates for serial order processing were comparable to
      neuropsychological measures and indicate that experimental serial order
      processing measures may be less susceptible to practice effects than traditional
      neuropsychological measures. Correlations were moderate and consistent with a
      global cognitive factor. Exploratory analyses indicated a potentially critical
      role of the Met allele of the Catechol-O-methyltransferase (COMT) Val158Met
      polymorphism in externally paced sequential recall. Experimental measures of
      serial order processing may reflect frontostriatal dysfunction and be a useful
      supplement to large neuropsychological batteries. 

PMID- 24119466
TI  - The management of severe hypertension in Australian general practice.
AB  - BACKGROUND: Severe hypertension (SHT) (Blood Pressure, BP >= 180/110 mmHg) is
      associated with considerable morbidity and mortality, yet little is known about
      how it is managed. The purpose of this study is to examine the management of SHT
      by Australian general practitioners (GPs) and to explore its variance across
      patient characteristics and clinical practices. METHODS: Review of electronic
      medical records for a year before and after a recorded measure of SHT in 7,499
      patients by 436 GPs in 167 clinics throughout Australia during 2008-2009. Outcome
      measures included follow-up, referral, changes to antihypertensive drug
      treatment, and BP control (normotensive reading, BP < 140/90 mmHg, and whether
      subsequent recorded measures were also in the normal range--sustained
      normotension). RESULTS: Of 7,499 patients with an electronic BP record of SHT,
      94% were followed up (median time 14 days); 8% were referred to an appropriate
      specialist (median time 89 days--2% within 7 days) and 86% were managed by GPs.
      GPs initiated or changed antihypertensive drugs in 5,398 patients (72% of
      cohort); of these, 46% remained hypertensive (4% with SHT) and 7% achieved
      sustained normotension; 6% had no further electronic BP records. The remaining
      14% had no medication changes; among these, 43% remained hypertensive (5% with
      SHT) and 3% achieved sustained normotension; 32% had no further electronic BP
      records. Some outcome measures displayed a variance across GP clinics that was
      mostly unexplained by patient or practice characteristics. CONCLUSIONS: Most
      patients with SHT had at least one follow-up visit and 72% had initiation of, or
      changes to, antihypertensive drug treatment. Although most of the patients
      experienced some improvement, blood pressure control was poor. Some clinics
      showed better performance. Suggestions are made for the development of clinical
      standards to facilitate appropriate management of this dangerous condition.

PMID- 24119467
TI  - The Aberdeen varicose vein questionnaire, patient factors and referral for
      treatment.
AB  - OBJECTIVES: It has been suggested that the Aberdeen Varicose Vein Questionnaire
      (AVVQ) could be used to help inform a patient pathway for referral and treatment
      of varicose veins. We aimed to determine 1) which patient and vein
      characteristics affected the AVVQ score, and 2) whether scores differed between
      those who were and were not offered treatment. METHODS: Patients completed the
      AVVQ at the clinic prior to being seen. Treatment was offered to patients with
      symptoms, and duplex detected truncal incompetence by surgeons blinded to the
      score. RESULTS: A total of 228 consecutive patients completed the AVVQ: 199 were
      valid questionnaires. On multivariate analysis, factors associated with a worse
      quality of life were female gender (p = .034, 3.14 mean unit increase in AVVQ),
      and bilateral varicose veins (10.25 unit increase, p < .001). For patients with
      C2 disease, only the presence of bilateral veins was significant. Overall, the
      AVVQ score was higher in those patients offered treatment than in those who were
      not (mean 20.3 [SD = 9.9] vs. 17.3 [SD = 10.3], p = .023), which equates to a
      2.74 unit increase. This was not significant in patients with C2 disease.
      CONCLUSION: It is unlikely that a threshold AVVQ score could be used to aid
      referral of patients with C2 disease. The distribution of veins (unilateral vs.
      bilateral) must be adjusted for when reporting AVVQ scores.

PMID- 24119468
TI  - Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free
      hemodialysis access patency of recurrent obstructive lesions.
AB  - OBJECTIVE: To explore the role of far infrared (FIR) radiation therapy for
      hemodialysis (HD) access maintenance after percutaneous transluminal
      angioplasties (PTA). METHODS: This was a prospective observational study.
      Eligible patients were those who received repeated PTA with the last PTA
      successfully performed within 1 week before the study enrollments. Consecutively
      enrolled patients undergoing successful HD treatments after PTA were randomly
      assigned to the FIR-radiated group or control group without radiation. FIR
      radiated therapy meaning 40-minute radiation at the major lesion site or
      anastomosed site three times a week was continued until an end-point defined as
      dysfunction-driven re-PTA or the study end was reached. RESULTS: Of 216
      participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR
      radiated participants and 48 control participants) and 119 with arteriovenous
      fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the
      FIR-radiated therapy compared with free-radiated usual therapy significantly
      enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p
      < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted
      for the overall improved patency rates (21.4% vs. 10.3%; p = .02). CONCLUSIONS:
      This study suggests FIR-radiated therapy improves PTA-unassisted patency in
      patients with AVG who have undergone previous PTA.

PMID- 24119469
TI  - On-label use of commercially-available abdominal endografts for para-anastomotic
      aneurysms and pseudoaneurysms after infrarenal abdominal aortic aneurysm open
      repair.
AB  - OBJECTIVES: To analyze feasibility and outcomes of endovascular aortic repair
      (EVAR) with a strictly on-label use of abdominal aortic endografts (OnL-EVAR) to
      treat para-anastomotic aneurysms (PAAs) and pseudoaneurysms (PSAs) after
      infrarenal abdominal aortic aneurysm open repair (OR). METHODS: The data of all
      consecutive patients treated between 1999 and 2012 for non-infected abdominal
      PAAs and PSAs at our center were prospectively collected. All cases fit for EVAR
      based on the instructions for use of a series of abdominal aortic endografts
      commercially available during the study period were scheduled for OnL-EVAR
      regardless of patients' surgical risk. Any patients unfit for OnL-EVAR underwent
      OR or other complex endovascular techniques. RESULTS: One hundred and forty-three
      patients were collected; 78 underwent OR and 65 endovascular repair with
      different strategies. Coil embolization, hybrid, and chimney/periscope grafts
      techniques were limited to seven patients unfit both for OR and OnL-EVAR.
      Inclusion criteria for OnL-EVAR were reached in 58 patients for an overall OnL
      EVAR feasibility of approximately 40% (21% for PAAs and 55% for PSAs). In
      particular, OnL-EVAR feasibility was 19% in case of involvement of proximal
      aortic anastomosis, 71% for distal aortic anastomosis, and 80% for iliac
      arteries. Overall, 25 aortouniiliac and 11 bifurcated implants were performed,
      single proximal aortic cuffs were used in 10 patients, and iliac extension in 12.
      Primary technical success was 98% without perioperative mortality. At a median
      follow-up of 67 months (range: 1-144 months), cumulative aneurysm-related
      mortality was 7%, endograft migration 7%, and reintervention was 17%. Life-table
      analysis showed actuarial survival and freedom from aneurysm-related death at 1,
      3, and 5 years of 100%, 98%, and 95%, and of 100%, 98%, and 95%, respectively.
      Freedom from aortic reintervention or open conversion at 1, 3, and 5 years was
      94%, 90%, and 85%. CONCLUSIONS: Feasibility of OnL-EVAR was limited for PAAs and
      PSAs, with a rate that was lower than 20% in case of involvement of proximal
      aortic anastomosis. Aortouniiliac configuration was the most commonly feasible
      implant and, despite strict on-label use of abdominal devices, the rate of late
      complications and reinterventions was high.

PMID- 24119471
TI  - Pelvic ring injuries in children. Part II: Treatment and results. A review of the
      literature.

PMID- 24119470
TI  - Program evaluation of a model to integrate internationally educated health
      professionals into clinical practice.
AB  - BACKGROUND: The demand for health professionals continues to increase, partially
      due to the aging population and the high proportion of practitioners nearing
      retirement. The University of British Columbia (UBC) has developed a program to
      address this demand, by providing support for internationally trained
      Physiotherapists in their preparation for taking the National Physiotherapy
      competency examinations.The aim was to create a program comprised of the
      educational tools and infrastructure to support internationally educated
      physiotherapists (IEPs) in their preparation for entry to practice in Canada and,
      to improve their pass rate on the national competency examination. METHODS: The
      program was developed using a logic model and evaluated using program evaluation
      methodology. Program tools and resources included educational modules and
      curricular packages which were developed and refined based on feedback from
      clinical experts, IEPs and clinical physical therapy mentors. An examination bank
      was created and used to include test-enhanced education. Clinical mentors were
      recruited and trained to provide clinical and cultural support for participants.
      RESULTS: The IEP program has recruited 124 IEPs, with 69 now integrated into the
      Canadian physiotherapy workforce, and more IEPs continuing to apply to the
      program. International graduates who participated in the program had an improved
      pass rate on the national Physiotherapy Competency Examination (PCE);
      participation in the program resulted in them having a 28% (95% CI, 2% to 59%)
      greater possibility of passing the written section than their counterparts who
      did not take the program. In 2010, 81% of all IEP candidates who completed the
      UBC program passed the written component, and 82% passed the clinical component.
      CONCLUSION: The program has proven to be successful and sustainable. This program
      model could be replicated to support the successful integration of other
      international health professionals into the workforce.

PMID- 24119472
TI  - The treatment of the proximal humeral fracture with the use of the PHN Nailing
      System: the importance of reduction.
AB  - PURPOSE OF THE STUDY: Intramedullary nailing is a minimally invasive technique
      that respects humeral head. However, limited surgical approach does not permit an
      anatomical reduction. The significance of the reduction on the functional outcome
      has not been sufficiently investigated. The aim of the study was to examine the
      functional and radiological postoperative outcome in patients with proximal
      humeral fractures treated with intramedullary nailing and the significance of
      reduction. MATERIALS AND METHODS: The study population consisted of 43 patients
      with proximal humeral fractures that were treated with the Proximal Humerus Nail
      System (Targon, Aesculap). Mean follow-up period was 23.2 months (SD: 8.9).
      Shoulder function was assessed with the Constant-Murley Score. Reduction was
      examined radiographically anteroposterior and true lateral plane. Radiographs of
      50 healthy shoulders served as controls. Malreduction was analyzed for 10 degrees
      , 15 degrees  and 20 degrees  in both planes. RESULTS: The overall functional
      results were satisfying; mean CS of all patients at the last follow-up visit was
      74.8 (SD: 19.3). Mean normalized CS for age and gender was 78.15 (SD 17.8).
      Fracture severity seemed to affect clinical outcome to a certain extent; 4-part
      fractures exhibited inferior results. Mean NSA was 126.5 (SD: 16.9) in
      anteroposterio and 137.4 (SD: 15.4) in true lateral view. The respective values
      in the control group were 134.1 degrees  (SD 7.1 degrees ) in anteroposterior and
      133.7 degrees  (SD 12.8 degrees ) in true lateral view. A malreduction of >20
      degrees  in the anteroposterior plane and >15 degrees  in both anteroposterior
      and true lateral planes resulted in significantly inferior clinical outcome.
      Thirteen complications were recorded, four of them being major. DISCUSSION The
      quality of reduction affected the postoperative outcome to a certain extent.
      Especially the anteroposterior reduction seemed to play a more important role in
      the postoperative function than reduction in the true lateral plane. However,
      this difference was statistically significant only after > 20 degrees 
      malreduction. The worst results in Constant Score were shown, as expected, in the
      group with malreduction in both planes; even a 15 degrees malreduction resulted
      in statistically significant difference. The importance of anteroposterior
      reduction could be due to achievement of better ROM in the frontal plane, most
      probably because of better levers on the tuberosities. However an absolute
      anatomical reduction does not have to be achieved at all costs. The overall good
      results of the fractures in this study despite absence of anatomical reduction
      could partly result from the limited surgical approach. CONCLUSIONS: The majority
      of the patients treated with closed reduction and internal fixation with PHN show
      good postoperative functional results. However, fracture malreduction reduction
      cannot be always avoided with the use of PHN. Nevertheless, the evaluation of the
      Constant-Murley score shows an absolute anatomical reduction in not necessary for
      satisfying functional outcome. The reduction in anteroposterior plane seems to
      play a more important role in the postsurgical functional outcome. A malreduction
      that exceeds 15 degrees  in both planes or a malreduction of more than 20 degrees
      in either plane should be avoided.

PMID- 24119473
TI  - [Evaluation of treatment outcomes in tuberculosis of knee and hip joints in 2005
      2012].
AB  - PURPOSE OF THE STUDY: Tuberculosis (TB) in a joint region presents high risk of
      damage to the joint. Consequences of a late diagnosis and inadequate therapy may
      be serious particularly in the large joints of lower extremities. Tuberculosis of
      knee and hip joints accounts for about 25% to 35% of osteoarticular tuberculosis
      (OAT). The aim of this study was to evaluate the objective and subjective results
      of tuberculosis treatment in knee and hip joints. MATERIAL AND METHODS: Of 258
      OAT patients treated at the Specialised Treatment Centre Jevicko between January
      2005 and September 2012, tuberculosis of the hip joint was diagnosed in 31
      patients in whom three hips were treated by incision and drainage and 10 by total
      hip replacement; 18 patients had tuberculosis of the knee joint with the
      following treatment: puncture in seven knees, incision and drainage in eight,
      excochleation of a tuberculous focus in the proximal tibia in two, removal of a
      bursa in one, arthrodesis in four and total knee replacement in four patients.
      The patients continued to be followed up at the Jevicko Centre. The scale of 1 to
      5 (best to worst) was established for evaluation of objective and subjective
      results of the treatment. The data were analysed using the basic statistical
      characteristics and compared. RESULTS: The objective evaluation was better for
      the hip joint; the sums of relative frequencies of marks 1 to 3 were 72.22% in
      the knee and 80.65% in the hip. In the knee more than 50% of the cases fell in
      the interval <1.304; 4.252>, in the hip this was <1.296; 3.672>. The hip joint
      was better subjectively evaluated, it had a higher sum of relative frequencies of
      marks 1 to 3, i.e., 96.77% as compared with 88.89% for the knee. In the knee more
      than 50% of the cases had marks in the interval <0.767; 3.122>; in the hip this
      was <0.869; 2.680>. The hip joint was better evaluated both objectively and
      subjectively. DISCUSSION: An early diagnosis allows for the treatment of
      synovitis, which has a better prognosis than an arthritic disease. The subjective
      perception of treatment results showed a better evaluation than its objective
      correlate. Many patients were satisfied with the results, even with an
      immobilised joint (in arthrodesis). Total joint replacement in OAT patients does
      not always provide expected results in either knee or hip joints. Arthrodesis
      also has its indications related to health condition, age and social status of
      the patient. In periprosthetic TB infections, a careful consideration should be
      given to removal of the prosthesis and its re-implantation in relation to all
      circumstances associated with each particular case. CONCLUSIONS: Tuberculosis of
      large weight-bearing joints is a rare entity in the countries with low TB
      prevalence, including the Czech Republic. It is necessary to pay attention to
      diagnosis and therapy and make them more effective even at higher costs
      associated with total hip replacement in TB or post-TB patients in order to
      maintain or restore joint function. At the time of borders open for citizens from
      countries with higher TB prevalence, the diagnosis of OAT should be considered.

PMID- 24119474
TI  - [Arthroscopic transcapsular iliopsoas tenotomy from the peripheral versus the
      central compartment in internal snapping hip syndrome. Short-term results of a
      prospective randomised study].
AB  - PURPOSE OF THE STUDY: In this prospective randomised study, the short-term
      results of arthroscopic transcapsular iliopsoas tenotomy approached from the
      peripheral versus the central compartment for internal snapping hip syndrome are
      presented. MATERIAL AND METHODS: A group of 19 patients (15 women and four men;
      mean age, 24.3 years) who underwent arthroscopic transcapsular iliopsoas tenotomy
      for internal snapping hip syndrome in the period between September 2010 and
      December 2011 were prospectively evaluated. No injury, hip surgery or feeling of
      hip instability was recorded in their personal histories. Radiographs did not
      show any dysplasia, retroversion of the acetabulum or cam lesions. The patients
      were allocated to two groups using sealed envelope randomisation: Group 1
      patients (n=10) were treated by tenotomy from the peripheral compartment and
      group 2 patients (n=9) underwent tenotomy from the central compartment during
      traction of the lower extremity. The evaluation included pre-operative 3T MRI
      findings, arthroscopically detected intra-articular lesions, duration of traction
      and post-operative complications. The pre-operative WOMAC scores were compared
      with those at one-year follow-up. In comparison of the two groups, the Mann
      Whitney exact test was used for WOMAC scores and Fisher's exact test for post
      operative complications. Statistical significance was set at a 0.05 level.
      RESULTS: In comparing post-operative complications, a significant difference
      (p=0.0468) between the groups was found only for genital paresthesia, which did
      not occur in group 1. The other differences were not statistically significant.
      The pre-operative WOMAC scores did not differ significantly between the groups
      (p=0.79). The post-operative WOMAC scores were significantly higher in group 1
      (p=0.02). In each group the change in WOMAC scores was different and was
      statistically significant in group 1 (p=0.0014). Associated intra-articular hip
      pathologies, most frequently synovitis of the peripheral compartment, acetabular
      chondropathy, or labral lesions, were diagnosed in 90% of group 1 patients and in
      66.7% of group 2 patients. DISCUSSION: Most of the authors comparing the results
      of two different ilioproas tenotomy techniques at one-year follow-up did not
      report any statistically significant differences in WOMAC scores between them. In
      accordance with the data reported, an increase in the post-operative WOMAC score,
      i.e., improvement of clinical outcome, was achieved in all our patients and, in
      group 1, it was significantly higher (p=0.0015), as compared with a similar study
      by Ilizaliturri. However, further follow-up of the patients and evaluation of
      long-term results will be necessary. CONCLUSIONS: The technique of arthroscopic
      ilioproas tenotomy approached from the peripheral compartment resulted in
      significantly fewer cases of genital paresthesia and provided significantly
      better clinical outcomes in comparison with tenotomy from the central
      compartment.

PMID- 24119475
TI  - [Accuracy of proximal femur correction achieved with LCP paediatric hip plates].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate, in comparison with
      the pre-operative planning, the accuracy of proximal femur correction achieved
      with the use of locking compression paediatric hip plates (LCP) in children and
      adolescents and to assess pre- and post-operative complications. MATERIAL AND
      METHODS: A group of 52 patients in whom proximal femoral osteotomy using the LCP
      was performed on a total of 55 hips between September 2009 and February 2013 were
      retrospectively evaluated. The following diagnoses were treated: unstable hip in
      cerebral palsy, 18 operations; Legg-Calve-Perthes disease, 10 operations; coxa
      vara of aetiology other than coxa vara adolescentium (CVA), eight operations;
      true CVA, six operations; femoral shortening by the Wagner method, six
      procedures; proximal femoral derotation osteotomy, four procedures; and post
      traumatic pseudoarthrosis of the proximal femur, three operations. RESULTS:
      Compared with the pre-operative plan, the average deviation of the colodiaphyseal
      angle was 5.2 degrees  (1 degrees  to 11 degrees ) in 18 unstable hips; 4.7
      degrees  (1 degrees  to 10 degrees ) in 10 cases of Legg-Calve-Perthes disease;
      4.5 degrees  (3 degrees  to 6 degrees ) in eight hips with coxa vara of aetiology
      other than CVA; 6.5 degrees  (2 degrees  to 13 degrees ) in six CVA hips; 4.5
      degrees  (1 degrees  to 10 degrees ) in six cases of femoral shortening; 3.5
      degrees  (1 degrees  to 5 degrees ) in four derotation osteotomies; and 3.7
      degrees  (0 degrees  to 6 degrees ) in three corrections of pseudoarthrosis. In
      one patient, osteosynthesis failed due to screws being pulled out from the
      proximal fragment; re-osteosynthesis was carried out using a conventional angled
      blade plate. DISCUSSION: As in other international studies, our results confirmed
      a high accuracy of proximal femur correction with use of the LCP instrumentation.
      The reported higher time requirement for this technique seems to be related to
      the learning curve and, with more frequent use, will probably be comparable to
      the time needed for application of conventional hip angled plates. CONCLUSIONS:
      The up-to-date LCP fixation system using the principle of angular stability for
      correction of the proximal femur in children is a clear advancement and its
      higher costs are certain to be outweighed by its higher accuracy and thus better
      results.

PMID- 24119476
TI  - Platelet-rich plasma injection is more effective than hyaluronic acid in the
      treatment of knee osteoarthritis.
AB  - PURPOSE OF THE STUDY: There is increasing use of platelet-rich plasma (PRP) in
      orthopaedics as it is a simple, cheap and minimally invasive technique. This
      study aimed to compare the effects of the use of PRP and hyaluronic acid (HA)
      injections in the knee of patients diagnosed with and being followed-up for
      degenerative arthritis. MATERIALS AND METHODS: This prospective study included 90
      patients with complaints of knee pain with findings of mild or moderate
      degenerative arthritis. In the PRP group (n=45), one intra-articular injection
      was applied and in the HA group (n=45), three doses of intra-articular injection
      were applied. Clinical evaluation was made by Knee Injury and Osteoarthritis
      Outcome Score (KOOS) and a visual pain scale. RESULTS: No severe adverse events
      was observed. Statistically significant better results in the KOOS score and
      visual pain scale was determined in PRP group than HA group at 3 months and 6
      months follow up. The cost of the application for the PRP group was lower than
      that of the HA group. CONCLUSION: The results of this study have shown the
      application of single dose PRP to be a safe, effective and low-cost method for
      treating OA. However, further studies are required for a more clear result.

PMID- 24119477
TI  - [Scapular fracture related to polytrauma severity in patients with serious
      brachial plexus palsy].
AB  - PURPOSE OF THE STUDY: Brachial plexus palsy is often accompanied by other
      injuries. Scapular fracture is thought to be a marker of polytrauma severity. The
      aim of this study was to evaluate associated injuries in patients with serious
      brachial plexus involvement and to determine whether there is a relationship
      between scapular fracture and severity of polytrauma in such patients. MATERIAL
      AND METHODS: We retrospectively evaluated 84 surgical patients who underwent
      brachial plexus reconstruction at our department between 2008 and 2011. In all of
      them, data on scapular fracture and major associated injuries were recorded.
      RESULTS: Of the 84 patients, 22 (26.2%) had a scapular fracture. Of 61 patients
      with upper plexus palsy only 10 (16.4%) suffered a scapular fracture while of 23
      patients with more severe plexus lesions 12 (52.2%, p<0.001) had fractured
      scapula. The ISS score in the patients with fractured scapula was significantly
      higher (51.8, SD=11, range=18-75, p<0.001). The patients with scapular fractures
      also had a significantly higher number of rib, clavicle, upper and lower limb
      fractures, and injuries to the thoracic organs and the head. CONCLUSIONS: Both
      scapular fracture and serious brachial plexus injury are usually associated with
      other severe injuries. They occur due to high-energy trauma. Generally, patients
      who sustain scapular fractures and upper limb impairment in motorcycle and car
      crashes are at high risk of other associated injuries and more severe polytrauma.

PMID- 24119478
TI  - Acetabular component position of the noncemented total hip endoprosthesis after
      previous Chiari pelvic osteotomy.
AB  - INTRODUCTION: The aim of the study was to determine the validity of acetabular
      component position of the noncemented total hip endoprosthesis after Chiari
      pelvic osteotomy. MATERIAL AND METHODS: The study involved 75 patients operated
      on at the Institute of Orthopedic Surgery "Banjica" in the period from 1990-2009.
      The first group consisted of 39 patients (46 hips) who underwent Chiari pelvic
      osteotomy and also later the implantation of a noncemented total hip
      endoprosthesis. A control group consisted of 36 patients (47 hips) who underwent
      total hip arthroplasty due to degenerative hip dysplasia. RESULTS: In the
      previously operated patients the centre of rotation of the hip was on the average
      placed more proximally, while in the control group of patients the position of
      the acetabular component was closer to the anatomical one. In the group of
      patients after Chiari osteotomy the mean acetabular cup abduction angle rated
      41.8 degrees +/-9.8 degrees , while in the control group this value was on the
      average higher (45.4 degrees +/-8.6 degrees ). DISCUSSION: There was a
      significant difference between the studied groups in relation to the distance
      between the acetabular component of endoprosthesis and the acetabular teardrop
      (t=-2.763; p=0.007). No statistically significant difference was determined in
      the mean value of the angle of acetabular abduction component of endoprosthesis
      between the studied groups of patients (t=1.878; p=0.064). CONCLUSIONS:
      Acetabular component position of the total hip endoprosthesis was not compromised
      by anatomic changes of the acetabulum caused by Chiari pelvic osteotomy.

PMID- 24119479
TI  - [A rare cause of lower limb venous thrombosis].

PMID- 24119480
TI  - Subacromial impingement syndrome in a patient with hereditary multiple exostosis:
      a case report.
AB  - BACKGROUND: Hereditary multiple exostosis (HME) is characterised by multiple
      osteochondromas that are distributed throughout the skeleton, invariably
      involving the shoulder girdle. Tumours within the subacromial space can cause
      secondary irritation of the rotator cuff and result in subacromial impingement
      syndrome. CASE PRESENTATION: We describe a 19 year old female patient with HME
      who presented with subacromial impingement syndrome secondary to a benign
      exostosis originating from the spine of the scapular and projecting into the
      subacromial space. CONCLUSION: The unique aspects of this report was that the
      origin of the exostosis, which was not observed on early standard radiographs of
      the shoulder, and the use of arthroscopic excision of the exostosis. Hence we
      believe a low threshold for additional imaging, such as a magnetic resonance
      imaging, should be considered for patients with HME with subacromial impingement
      syndrome to ensure a symptomatic exostosis is not neglected. Arthroscopic
      excision of a benign subacromial exostosis is effective, offering a minimally
      invasive approach with relief of the patient's symptoms.

PMID- 24119481
TI  - Controlled hypertension induces cerebrovascular and gene alterations in Cyp1a1
      Ren2 transgenic rats.
AB  - Hypertension is a major risk factor for small vessel disease and dementia, but
      the pathogenic mechanisms are not fully known. This study aimed to assess
      cerebrovascular alterations in response to different durations (4 or 6 months) of
      controlled hypertension in an inducible transgenic rat model of hypertension
      (Cyp1a1-Ren2) as compared with normotensive litter mate controls. After 6 months
      of hypertension as compared with controls, a significant reduction in vascular
      width was paralleled by an increase in the protein levels of claudin-5, an
      endothelial tight junction protein. Notably, vascular alterations were associated
      with increased microglia, and these changes were preceded by increased eNOS
      expression. Investigation of global gene expression by microarray analysis
      indicated alterations in predominantly growth factor related genes. Herein, we
      show that modest, sustained levels of hypertension are sufficient to cause
      cerebrovascular alterations accompanied by endothelial and inflammatory changes.
      These changes are paralleled by alterations in growth factor expression
      suggestive of a mechanistic role. 

PMID- 24119482
TI  - Triple therapy with first-generation protease inhibitors for patients with
      genotype 1 chronic hepatitis C: recommendations of the Italian association for
      the study of the liver (AISF).
AB  - The first-generation Protease Inhibitors Boceprevir and Telaprevir administered
      in triple therapy regimens with Peg-interferon alpha and Ribavirin have been
      proven effective in increasing the rate of Sustained Virological Response in both
      naive and treatment-experienced patients with chronic genotype-1 hepatitis C.
      However, at the individual level, the therapeutic advantage of triple therapy is
      highly variable and results from the combination of multiple factors related to
      the characteristics of patient, viral status and liver disease. The
      recommendations presented are promoted by the Italian Association for the Study
      of the Liver, with the aim to help the physician in the decision-making process
      as well as to manage patients during treatment with triple therapy. 

PMID- 24119483
TI  - Impact of emerging hepatitis C virus treatments on future needs for liver
      transplantation in France: a modelling approach.
AB  - BACKGROUND: In light of the impact of emerging hepatitis C virus treatments on
      morbidity and mortality, we sought to determine whether candidates for liver
      transplantation for hepatocellular carcinoma and decompensated cirrhosis will
      decrease sufficiently to match liver grafts for hepatitis C virus-infected
      patients. AIMS: Using a Markov model, we quantified future liver graft needs for
      hepatitis C virus-induced diseases and estimated the impact of current and
      emerging treatments. METHODS: We simulated progression of yearly-hepatitis-C
      virus-infected cohorts from the beginning of the epidemic and calculated 2013
      2022 candidates for liver transplantation up until 2022 without and with
      therapies. We compared these estimated numbers to projected trends in liver
      grafts for hepatitis C virus. RESULTS: Overall, current treatment would avoid
      transplantation of 4425 (4183-4684) potential candidates during the period 2013
      2022. It would enable an 88% and 42% reduction in the gap between liver
      transplantation activity and candidates for hepatocellular carcinoma and
      decompensated cirrhosis, respectively. Emerging hepatitis C virus treatments
      would allow adequacy in transplant activities for hepatocellular carcinoma.
      However, they would not lead to adequacy in decompensated cirrhosis from 2013 to
      2022. Results were robust to sensitivity analysis. CONCLUSION: Our study
      indicates that patients will benefit from public health policies regarding
      hepatitis C virus screening and therapeutic access to new emerging treatments.

PMID- 24119484
TI  - Isothermal titration calorimetry in membrane protein research.
AB  - Isothermal titration calorimetry is a versatile method to characterize energetics
      of intermolecular reactions and in particular interactions between drug molecules
      and their macromolecular targets. The assay is widely used in medicinal chemistry
      to quantification and characterization of molecular mechanisms of these
      interactions. The article reviews applications of the method to study ligand
      interactions with various classes of embedded membrane proteins. These proteins
      constitute very important fraction of macromolecular targets for medicinal
      compounds used in current therapies and recently emerged for detailed structural,
      functional and biochemical characterization of their interactions with drug
      molecules. 

PMID- 24119485
TI  - Recapitulation of characteristics of human placental vascular insufficiency in a
      novel mouse model.
AB  - OBJECTIVE: We tested the effects of selective reduction of placental blood flow
      by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth
      restriction (FGR). METHODS: Timed mated C57BL/6J Day(D) 18 dams were divided into
      two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20,
      cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks.
      Outcome data included birth and placental weight, postnatal growth, placental
      volume determined by stereology, quantification of placental insulin-like growth
      factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and
      gene expression by qPCR and GeneChip microarray analysis. RESULTS: Compared with
      control, MUAL had an 11% reduction in mean birth weight (1.06 +/- 0.13 g vs. 0.94
      +/- 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age,
      mean body weights of MUAL pups were significantly lower than sham. By 8 weeks,
      males but not females MUAL mice achieved equivalent mean body weight to control.
      Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2
      were significantly reduced by MUAL. In contrast, placental protein level of IGFBP
      2 and 6 were significantly elevated in the MUAL. Genomic expression analysis
      demonstrated that MUAL pups significantly up-regulated genes that were associated
      with apoptosis and growth pathways. CONCLUSION: This novel mouse animal model of
      FGR using selective ligation recapitulates multiple characteristics of placental
      vascular insufficiency (PI) in humans. This is the first non-genetic mouse model
      of PI which offers its application in transgenic mice to better study the
      underlying mechanisms in PI. CONDENSATION: A new mouse model of placental
      vascular insufficiency by selective ligation of mesenteric uterine artery branch
      recapitulates multiple findings observed in human placental vascular
      insufficiency.

PMID- 24119486
TI  - Enhanced gas chromatography-mass spectrometry method for bacterial
      polyhydroxyalkanoates analysis.
AB  - A gas chromatography-mass spectrometry method for quantification of
      polyhydroxyalkanoates (PHAs), containing 4-carbon to 16-carbon monomers, even in
      the absence of standards, was developed. Strong linear correlations existed
      between PHA carbon number and retention time/response factor (R(2) >= 0.987).
      Based on the correlations, high recovery values, between 100.5% and 114.3%, were
      obtained for PHA polymers.

PMID- 24119488
TI  - HPV: a factor in organ preservation for locally advanced larynx and hypopharynx
      cancer?
AB  - PURPOSE/OBJECTIVE: To assess the interaction of HPV/p16 status and therapy
      rendered in patients with locally advanced squamous cell carcinoma of the larynx
      and hypopharynx. MATERIALS AND METHODS: Forty-seven consecutive patients
      receiving definitive treatment between 2009 and 2011 for locally advanced larynx
      or hypopharynx cancer with high-risk HPV and/or p16 testing performed were
      identified and retrospectively investigated. Overall survival (OS), disease-free
      survival (DFS), and local recurrence-free survival (LRFS) were assessed. RESULTS:
      Of 47 evaluable patients, there were 38 (81%) with laryngeal and 9 (19%) with
      hypopharyngeal tumors, 13 (28%) of which were found to be either HPV or p16
      positive. At a median follow-up of 24 months, comparing HPV/p16+ versus HPV/p16-
      patients, there was no difference in OS, DFS, or LRFS. There was an improvement
      in 2-year DFS (60% vs 100%, P=.03) and LRFS (80% vs 100%, P=.08), in HPV/p16+
      patients treated with chemo/RT versus surgery. There was an improvement in 2-year
      DFS (100% vs 68%, P=.04) and LRFS (100% vs 72%, P=.05) in HPV/p16+ versus HPV/p16
      patients who received chemo/RT. CONCLUSIONS: Patients with HPV/p16+ tumors fared
      more favorably with chemo/RT than up-front surgery, with improvements in DFS and
      LRFS. In patients treated with the intent of organ preservation therapy, HPV/p16+
      patients had no observed treatment failures. HPV/p16 status should be taken into
      account when considering organ preservation for locally advanced larynx and
      hypopharynx cancers.

PMID- 24119487
TI  - Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the
      incidence of posttraumatic stress after acute myocardial infarction through
      trauma-focused psychological counseling: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Posttraumatic Stress Disorder (PTSD) may occur in patients after
      exposure to a life-threatening illness. About one out of six patients develop
      clinically relevant levels of PTSD symptoms after acute myocardial infarction
      (MI). Symptoms of PTSD are associated with impaired quality of life and increase
      the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT
      study is that trauma-focused psychological counseling is more effective than non
      trauma focused counseling in preventing posttraumatic stress after acute MI.
      METHODS/DESIGN: The study is a single-center, randomized controlled psychological
      trial with two active intervention arms. The sample consists of 426 patients aged
      18 years or older who are at 'high risk' to develop clinically relevant
      posttraumatic stress symptoms. 'High risk' patients are identified with three
      single-item questions with a numeric rating scale (0 to 10) asking about 'pain
      during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless
      when being told about having MI'. Exclusion criteria are emergency heart surgery,
      severe comorbidities, current severe depression, disorientation, cognitive
      impairment and suicidal ideation. Patients will be randomly allocated to a single
      45-minute counseling session targeting either specific MI-triggered traumatic
      reactions (that is, the verum intervention) or the general role of psychosocial
      stress in coronary heart disease (that is, the control intervention). The session
      will take place in the coronary care unit within 48 hours, by the bedside, after
      patients have reached stable circulatory conditions. Each patient will
      additionally receive an illustrated information booklet as study material.
      Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk
      factors will be assessed during hospitalization. The primary outcome is the
      interviewer-rated posttraumatic stress level at three-month follow-up, which is
      hypothesized to be at least 20% lower in the verum group than in the control
      group using the t-test. Secondary outcomes are posttraumatic stress levels at 12
      month follow-up, and psychosocial functioning and cardiometabolic risk factors at
      both follow-up assessments. DISCUSSION: If the verum intervention proves to be
      effective, the study will be the first to show that a brief trauma-focused
      psychological intervention delivered within a somatic health care setting can
      reduce the incidence of posttraumatic stress in acute MI patients. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01781247.

PMID- 24119489
TI  - Connexin 32 and 43 mutations: do they play a role in chronic rhinosinusitis?
AB  - OBJECTIVE: Dysfunction of the sinonasal epithelium may contribute to the
      pathogenesis of chronic rhinosinusitis (CRS) including recurrent acute
      rhinosinusitis (RARS). Mutations in connexin 32 and 43 proteins have been
      associated with a number of human diseases. The objective of this study is to
      investigate the role of mutations in connexin 32 or connexin 43 genes in CRS and
      RARS. METHODS: Prospective case series of 19 patients with CRS and /or RARS.
      Clinical and demographic factors were noted and buccal swabs were collected for
      DNA sequencing of connexin 32 and connexin 43 genes. RESULTS: One patient was
      found to have a conservative V193I mutation in the connexin 32 gene. Connexin 43
      mutations were found in two patients - a silent R239R mutation and an AAA
      insertion after the stop codon in the 3' UTR. None of these mutations are
      associated with any known diseases or predicted to lead to protein dysfunction.
      CONCLUSION: Mutations in connexin 32 or 43 genes in patients with CRS, including
      RARS, appear to be rare. The etiologic role of connexin mutations in chromic
      rhinosinusitis is suspect, and routine sequencing for connexin mutations in
      patients with RARS or CRS is not cost effective.

PMID- 24119490
TI  - The protective effect of Salvia miltiorrhiza on gentamicin-induced ototoxicity.
AB  - OBJECTIVE: The clinical use of aminoglycoside antibiotics is limited in most
      countries because of auditory toxicity side effects. However, their use is common
      in developing countries because they are inexpensive and convenient. Salvia
      miltiorrhiza extracts are used clinically in China for their antioxidant
      properties. We investigated the effect of a clinically approved injectable S.
      miltiorrhiza solution on inducible nitric oxide synthase (iNOS) generation
      induced by the aminoglycoside antibiotic gentamicin and an ototoxicity protective
      mechanism. METHODS: Sixty adult guinea pigs were used in this study and divided
      into four groups. Auditory brainstem response (ABR) testing was performed before
      and after treatments and animals were sacrificed for morphological and
      immunostaining assays after determining threshold shifts in ABR. The cochleae
      were examined by transmission electron microscopy (TEM) and scanning electron
      microscopy (SEM) to observe ultrastructural changes. In addition, hair cell loss,
      iNOS and caspase-3 expression, and apoptosis were measured. RESULTS: The result
      showed that hearing loss, iNOS overexpression accompanied with disorganization in
      the cochlea, and terminal deoxynucleotidyl transferase- mediated dUTP- biotin
      nick end labeling (TUNEL)-stained positive cells in animals treated with
      gentamicin. However, pretreatment with S. miltiorrhiza (3g/kg/day for 10 days)
      decreased gentamicin-induced hearing loss, attenuated iNOS and caspase-3
      expression, and decreased the number of apoptotic cells. Furthermore, it also
      reduced the ultrastructural damage due to ototoxicity as observed by SEM and TEM.
      CONCLUSIONS: These findings indicate that S. miltiorrhiza protects against
      gentamicin-induced ototoxicity and could apply to the protection of ototoxicity.

PMID- 24119491
TI  - A new way to treat forearm post-traumatic non-union in young patients with
      intramedullary nailing and platelet-rich plasma.
AB  - INTRODUCTION: Non-union rate in forearm fractures is generally less than 2% when
      a proper technique is used; this rate increases when ulnar lesions are involved.
      PATIENTS AND METHODS: We present a case series of seven young patients whose
      average age was 14 years (range 11-19 years) at the time of surgery and who
      presented with a forearm post-traumatic non-union that was previously treated in
      different ways (three isolated ulnar non-union, two isolated radial non-union and
      two combined). Average follow-up was 34 months (range 9-72 months). Surgical
      treatment began with the removal of the previous synthesis and with curettage of
      the non-union area. The Acumed ulnar rod, Acumed radial rod and Thalon elastic
      nail (all of them are unreamed and locked nails) together with autologous
      platelet-rich plasma (PRP) obtained with the Biomet System (concentration of
      158.2*10(4) platelets/MUL) were chosen to treat the patients. X-rays and clinical
      controls were conducted every 30 days until recovery. RESULTS: All patients
      recovered: average recovery was 23 weeks from operation (range 16-36 weeks) and
      nails were removed 3 months after complete healing. Six patients had excellent
      results and one patient had a good result (Patient 2, forearm pronosupination 60
      0-40 degrees). DISCUSSION: The purpose of the case series was to establish a
      better way of treatment and to find a technique that could avoid the use of bone
      grafts, because obtaining autologous bone requires a further surgical procedure
      that can be really invasive depending on the amount of bone needed. CONCLUSION:
      All patients in the study showed complete recovery, with excellent clinical
      outcomes. Although there were only seven patients in this case series, and there
      is a need to analyse more patients, this study showed that the use of a specific
      locking nail system can provide proper stability to ulnar or radial atrophic non
      union despite rotational forces, and when combined with autologous growth factors
      (PRP) is sufficient to promote bone healing in young patients without the
      necessity to take autologous bone grafts.

PMID- 24119492
TI  - Revision of 120 tibial infected non-unions with bone and soft tissue loss treated
      with epidermato-fascial osteoplasty according to Umiarov.
AB  - Treatment of tibial infected non-unions with bone and soft tissue loss has to
      solve three problems: infection, lack of bone continuity and lack of skin
      coverage. The aims of treatment are infection healing, bone consolidation with
      preservation of limb length and soft tissue reconstruction. The most important
      stage in the planning is an accurate debridement. Soft tissue reconstruction can
      be achieved using plastic surgery, and bone reconstruction is accomplished with
      bone grafts or induced membrane technique, but these methods may present
      disadvantages and risks. Epidermato-fascial osteoplasty is a modified procedure
      of compression-distraction osteosynthesis that was first described by Umiarov in
      1982. This procedure offers the advantages of exactly classifying the phases of
      simultaneous bone and soft tissue regeneration, and of eliminating large tissue
      losses without previous closure of soft tissues or use of grafts, because the
      transported fragment takes fascia and skin along during the transport and closes
      the edges of the soft tissue gap until the epidermic and fascial reconstruction
      is complete. A total of 120 patients underwent this kind of surgery between 1986
      and 2010 and were followed up for 2-26 years. Average age was 34 years (range 21
      57 years). Cultures were positive for Staphylococcus in all cases, and for
      Pseudomonas in 27 cases. Adequate antibiotic therapy was administered in
      collaboration with the Infectious Diseases Specialist. Tibial bone resection was
      from 6 to 18cm (average 9.5cm). The Ilizarov apparatus was used with the oblique
      wire technique for bone transport in all patients. No intraoperative
      complications were observed. One patient died 40 days after the operation because
      of pulmonary embolism. The duration of treatment for the remaining 119 patients
      was 7-18 months. In all cases, infection eradication, healing of regenerate bone,
      consolidation at the docking site (with the aid of an autoplastic bone graft in
      only 11 patients), and epidermic and fascial reconstruction were observed, and
      functional results were very good. These techniques are particularly demanding
      for the patient and for the surgical team, but our results demonstrate that they
      can provide excellent outcomes in the management of difficult cases of infected
      non-unions. 

PMID- 24119493
TI  - Retrospective analysis of incidence of peroneal artery hypoplasia in 101 free
      fibula transfers and new classification of popliteal branch anomalies.
AB  - It is generally recognised by surgeons that there are anatomical variations of
      the popliteal artery and its branches, and knowledge of these has important
      clinical implications for fibula flap harvest. The aim of this study was to
      report our experience on 101 fibula free flaps, highlighting a new type of
      anatomical variation of the peroneal artery in a patient undergoing
      osteocutaneous fibula free flap for tibial reconstruction. During flap harvest,
      the peroneal vascular pedicle was shown to be hypoplastic and aberrant to its
      origin, branching between the proximal and medium third of the leg from the
      posterior tibialis artery with a diameter of 1mm. A modification of Kim's
      classification with the addition of a further "type IIID" group is suggested, to
      include peroneal artery hypoplasia or aplasia. This is an uncommon case of a rare
      infrapopliteal branching pattern that was undetected clinically and
      sonographically, exposing both the surgeon and patient to high risk of flap
      failure and/or leg ischaemic complication. Surgeons conducting free fibula
      transfer surgery should be aware of such a possibility as well as other
      variations, and could consider performing routine angiographic study on the donor
      limb, or they may be skilful enough to apply instant tricks to enable them to
      conduct the procedure safely. 

PMID- 24119494
TI  - Interprosthetic femoral fractures-A challenge of treatment. A systematic review
      of the literature.
AB  - The success of prosthetic surgery has led to an increase in the percentage of the
      population having more than one prosthetic implant. This, combined with an
      increase in the average life expectancy and functional requirements for the
      elderly, has led to a higher incidence of periprosthetic and interprosthetic
      fractures. More precisely, the femoral shaft is compressed between two
      ipsilateral implants with most of these fractures being located on the
      supracondylar femoral shaft. Their treatment is not only technically demanding
      and challenging, but can also be associated with serious complications. Treatment
      must be determined and assessed according to the type of fracture, the stability
      of the prosthesis, the bone quality and the general condition of the patient.
      There is little information in the literature about this type of injury: there
      are several published case reports detailing unconventional solutions and the
      case studies presented are limited and not significant. This review aims to
      provide an updated and comprehensive list of diagnostic and therapeutic protocols
      accepted today, while recognising that these protocols are being continuously
      updated according to experience gained. 

PMID- 24119495
TI  - The thickness of the anterior compartment does not indicate compartment syndrome
      in acutely traumatised legs?
AB  - BACKGROUND: The study was conducted to achieve early detection of increased
      compartment pressure by comparing the changes between the thickness and pressure
      within the musculofascial compartments after lower leg injury. METHODS: We
      included cases of a lower-leg fracture between January and December 2007.
      Bilateral lower leg compartment pressure and thickness were measured before the
      surgery and post-anaesthesia, and the surgery was performed within 12 h after the
      initial trauma. The intracompartment pressure (ICP) was measured with a Wick
      catheter pressure monitor. The thickness (width) of the anterior compartment of
      lower leg was measured using ultrasound. RESULTS: All data were measured within 4
      6h of the injury. The average thickness in injured legs versus uninjured was 30
      mm (15-46 mm) versus 20.4 mm (13-30 mm), P<0.001. The average intracompartment
      pressure (ICP) in injured leg versus uninjured was 45.3 mmHg (26-80 mmHg) versus
      17.5 mmHg (15-20 mmHg), P<0.001. The thickness and ICP were significantly
      increased for injured lower legs compared to the uninjured legs, but the increase
      in ICP did not show a significant relationship with the change in thickness of
      the injured lower leg. CONCLUSION: In this study, the results of ICP and
      thickness changes of injury lower leg compared with uninjured leg revealed no
      statistically significant correlation. Some injuries showed a high ICP with only
      mild changes in thickness, while some showed a high ICP with significant changes.
      Although ultrasound has many advantages for the evaluation of soft tissue changes
      after trauma, this study revealed that thickness changes are not a predicable
      parameter for determining pressure on the acute fracture of lower leg.

PMID- 24119496
TI  - Penetrating thorax injury leads to mild systemic activation of neutrophils
      without inflammatory complications.
AB  - INTRODUCTION: Trauma is one of the major causes of morbidity and mortality.
      Thoracic injuries are associated with inflammatory complications such as ARDS.
      The pathogenesis of this complication after pulmonary injury is incompletely
      understood, but neutrophils are thought to play a pivotal role. The aim of this
      project was to gain more insight in the role of thoracic injuries in the
      pathophysiological processes that link systemic neutrophil activation with
      inflammatory complications after trauma. METHODS: In this prospective cohort
      study fifty-five patients with isolated penetrating thoracic injury were included
      at a level one Trauma Unit. Blood samples were analysed for neutrophil phenotype
      with the use of flowcytometry within 3 h of trauma and repeated six and 24 h
      after injury. The presence of inflammatory complications (e.g. ARDS or
      sepsis/septic shock) was assessed during admission, and this was related to the
      neutrophil phenotpe. RESULTS: The clinical follow-up of fifty-three patients was
      uneventful. Only two patients developed an inflammatory complication. Within 3 h
      after trauma, neutrophils showed a decreased expression of FcgammaRII (p=0.007)
      and FcgammaRIII (p=0.001) compared to healthy individuals. After 6 h, expression
      of active FcgammaRII (p=0.017), C5aR (p=0.004) and CAECAM8 (p=0.043) increased,
      whereas L-selectin (p=0.002) decreased. After 24 h also CXCR-2 (CD182) expression
      increased compared to healthy individuals (p=0.001). CONCLUSIONS: Penetrating
      thoracic trauma leads to a distinct primed activation status of circulating
      neutrophils within hours. In addition to activation of cells, both young and
      reverse migrated neutrophils are released into the circulation. This degree of
      systemic inflammation does not exceed a threshold of inflammation that is needed
      for the development of inflammatory complications like ARDS.

PMID- 24119497
TI  - Pulmonary artery pseudoaneurysm after a left upper sleeve lobectomy.
AB  - A 55-year-old man was re-admitted for persistent hemoptysis and high fever three
      weeks after an initial left upper sleeve lobectomy for a central squamous lung
      cancer tumor. Pulmonary artery pseudoaneurysm and pulmonary infection were
      confirmed by multidetector computed tomography angiography and subsequent
      emergency completion pneumonectomy. The development of pulmonary artery
      pseudoaneurysm, secondary to post-operative pulmonary infection and pulmonary
      vascular manipulation, is rare and prompt surgical manipulation is mandatory. 

PMID- 24119498
TI  - Energy intensity, life-cycle greenhouse gas emissions, and economic assessment of
      liquid biofuel pipelines.
AB  - Petroleum fuels are predominantly transported domestically by pipelines, whereas
      biofuels are almost exclusively transported by rail, barge, and truck. As biofuel
      production increases, new pipelines may become economically attractive. Location
      specific variables impacting pipeline viability include construction costs,
      availability and costs of alternative transportation modes, electricity prices
      and emissions (if priced), throughput, and subsurface temperature. When
      transporting alcohol or diesel-like fuels, pipelines have a lower direct energy
      intensity than rail, barge, and trucks if fluid velocity is under 1 m/s for 4
      inch diameter pipelines and 2 m/s for 8-inch or larger pipelines. Across multiple
      hypothetical state-specific scenarios, profit-maximizing design velocities range
      from 1.2 to 1.9 m/s. In costs and GHG emissions, optimized pipelines outperform
      trucks in each state and rail and barge in most states, if projected throughput
      exceeds four billion liters/year. If emissions are priced, optimum design
      diameters typically increase to reduce pumping energy demands, increasing the
      cost-effectiveness of pipeline projects.

PMID- 24119499
TI  - Environmental impact of submerged anaerobic MBR (SAnMBR) technology used to treat
      urban wastewater at different temperatures.
AB  - The objective of this study was to assess the environmental impact of a submerged
      anaerobic MBR (SAnMBR) system in the treatment of urban wastewater at different
      temperatures: ambient temperature (20 and 33 degrees C), and a controlled
      temperature (33 degrees C). To this end, an overall energy balance (OEB) and life
      cycle assessment (LCA), both based on real process data, were carried out. Four
      factors were considered in this study: (1) energy consumption during wastewater
      treatment; (2) energy recovered from biogas capture; (3) potential recovery of
      nutrients from the final effluent; and (4) sludge disposal. The OEB and LCA
      showed SAnMBR to be a promising technology for treating urban wastewater at
      ambient temperature (OEB=0.19 kW h m(-3)). LCA results reinforce the importance
      of maximising the recovery of nutrients (environmental impact in eutrophication
      can be reduced up to 45%) and dissolved methane (positive environmental impact
      can be obtained) from SAnMBR effluent.

PMID- 24119500
TI  - A population-based analysis of leaving the hospital against medical advice:
      incidence and associated variables.
AB  - BACKGROUND: Prior studies of patients leaving hospital against medical advice
      (AMA) have been limited by not being population-based or assessing only one type
      of patient. METHODS: We used administrative data at the Manitoba Centre for
      Health Policy to evaluate all adult residents of Manitoba, Canada discharged
      alive from acute care hospitals between April 1, 1990 and February 28, 2009. We
      identified the rate of leaving AMA, and used multivariable logistic regression to
      identify socio-demographic and diagnostic variables associated with leaving AMA.
      RESULTS: Of 1,916,104 live hospital discharges, 21,417 (1.11%) ended with the
      patient leaving AMA. The cohort contained 610,187 individuals, of whom 12,588
      (2.06%) left AMA once and another 2986 (0.49%) left AMA more than once. The
      proportion of AMA discharges did not change over time. Alcohol and drug abuse was
      the diagnostic group with the highest proportion of AMA discharges, at 11.71%.
      Having left AMA previously had the strongest association with leaving AMA (odds
      ratio 170, 95% confidence interval 156-185). Leaving AMA was more common among
      men, those with lower average household incomes, histories of alcohol or drug
      abuse or HIV/AIDS. Major surgical procedures were associated with a much lower
      chance of leaving the hospital AMA. CONCLUSIONS: The rate of leaving hospital AMA
      did not systematically change over time, but did vary based on patient and
      illness characteristics. Having left AMA in the past was highly predictive of
      subsequent AMA events.

PMID- 24119501
TI  - Xylo- and cello-oligosaccharide oxidation by gluco-oligosaccharide oxidase from
      Sarocladium strictum and variants with reduced substrate inhibition.
AB  - BACKGROUND: The oxidation of carbohydrates from lignocellulose can facilitate the
      synthesis of new biopolymers and biochemicals, and also reduce sugar metabolism
      by lignocellulolytic microorganisms, reserving aldonates for fermentation to
      biofuels. Although oxidoreductases that oxidize cellulosic hydrolysates have been
      well characterized, none have been reported to oxidize substituted or branched
      xylo-oligosaccharides. Moreover, this is the first report that identifies amino
      acid substitutions leading to GOOX variants with reduced substrate inhibition.
      RESULTS: The recombinant wild type gluco-oligosaccharide oxidase (GOOX) from the
      fungus Sarocladium strictum, along with variants that were generated by site
      directed mutagenesis, retained the FAD cofactor, and showed high activity on
      cello-oligosaccharide and xylo-oligosaccharides, including substituted and
      branched xylo-oligosaccharides. Mass spectrometric analyses confirmed that GOOX
      introduces one oxygen atom to oxidized products, and 1H NMR and tandem mass
      spectrometry analysis confirmed that oxidation was restricted to the anomeric
      carbon. The A38V mutation, which is close to a predicted divalent ion-binding
      site in the FAD-binding domain of GOOX but 30 A away from the active site,
      significantly increased the kcat and catalytic efficiency of the enzyme on all
      oligosaccharides. Eight amino acid substitutions were separately introduced to
      the substrate-binding domain of GOOX-VN (at positions Y72, E247, W351, Q353 and
      Q384). In all cases, the Km of the enzyme variant was higher than that of GOOX,
      supporting the role of corresponding residues in substrate binding. Most notably,
      W351A increased Km values by up to two orders of magnitude while also increasing
      kcat up to 3-fold on cello- and xylo-oligosaccharides and showing no substrate
      inhibition. CONCLUSIONS: This study provides further evidence that S. strictum
      GOOX has broader substrate specificity than the enzyme name implies, and that
      substrate inhibition can be reduced by removing aromatic side chains in the -2
      binding subsite. Of the enzyme variants, W351A might be particularly advantageous
      when oxidizing oligosaccharides present at high substrate concentrations often
      experienced in industrial processes.

PMID- 24119502
TI  - Gadolinium complex and phosphorescent probe-modified NaDyF4 nanorods for T1- and
      T2-weighted MRI/CT/phosphorescence multimodality imaging.
AB  - To compensate for the deficiencies of individual imaging modalities, lanthanide
      based nanoparticles are ideal building blocks for multifunctional contrast
      agents. Herein, oleic acid-coated NaDyF4 nanorods (DyNPs) were synthesized by the
      hydrothermal method, and then coated with alpha-cyclodextrin (alpha-CD) and
      modified with gadolinium complex (Gd-DTPA) to obtain hydrophilic and
      functionalized nanoparticles (DyNPs-Gd). By loading the phosphorescent probe
      (iridium-complex) within the surface hydrophobic layer, the developed
      nanophosphors (DyNPs-Gd-Ir) could be further applied in phosphorescent cell
      labeling. The Dy in the host induces a high X-ray absorption ability for X-ray
      computed tomography (CT) and negative enhancement for T2-weighted magnetic
      resonance imaging (MRI), whereas positive contrast for T1-weighted MRI results
      from the Gd-DTPA. DyNPs-Gd-Ir has been successfully applied to T1- and T2
      weighted MRI/CT in vivo. Toxicity studies demonstrated that DyNPs-Gd-Ir exhibited
      low toxicity to living systems. Therefore, DyNPs-Gd-Ir could be a platform for
      next-generation contrast agents for T1- and T2-weighted MRI/CT/phosphorescence
      multimodal imaging.

PMID- 24119503
TI  - Longitudinal and secular trends in dietary supplement use: Nurses' Health Study
      and Health Professionals Follow-Up Study, 1986-2006.
AB  - Most studies on the prevalence of supplement use in the United States were cross
      sectional or evaluated trends in limited variety of supplements. The objective of
      this study was to describe the longitudinal and secular trend of dietary
      supplement use over the past 20 years in health professionals using data from two
      large prospective cohorts. We analyzed cohort data from 1986 to 2006 in the
      Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS).
      In 1986, 74,194 women aged 40 to 65 years in the NHS and 50,497 men aged 40 to 75
      years in the HPFS were included. Use of dietary supplements including
      multivitamins, vitamins, and minerals was repeatedly asked every 4 years.
      Generalized estimating equation models were used for repeated analysis.
      Prevalence of use of any supplement increased among both women (71.3% to 88.3%)
      and men (56.4% to 80.7%) from 1986 to 2006. Notably, longitudinal increases in
      the prevalence of use of vitamin D (2.2% to 32.2% for women and 1.1% to 6.7% for
      men), folic acid (0.8% to 10.7% for women and 1.1% to 13.8% for men), and fish
      oil (1.6% to 18.1% for women and 3.3% to 22.2% for men) supplements were observed
      from 1990 to 2006. However, the use of vitamin A, beta carotene, vitamin C, and
      vitamin E supplements peaked in 1994 or 1998, then declined steadily. A secular
      increase in use of multivitamins, vitamin D, folic acid, and fish oil across same
      age group was noted. In conclusion, the use of many types of dietary supplements
      has increased over time, but the use of antioxidant supplements has declined. The
      secular increase in the prevalence of use of supplements across the same age
      group suggests that aging of the population is not the primary reason for the
      increase. These findings in health professionals need to be replicated in the
      general populations. 

PMID- 24119504
TI  - Medication-associated lesions of the GI tract.

PMID- 24119505
TI  - Granulocytic sarcoma of the ileum observed by double-balloon endoscopy before
      treatment (with video).

PMID- 24119506
TI  - Variable interpretation of polyp size by using open forceps by experienced
      colonoscopists.
AB  - BACKGROUND: Endoscopic measurement of colorectal polyps by using open forceps is
      commonly used in clinical trials but is subject to several sources of error.
      OBJECTIVE: Assess error rates in polyp size determination with open forceps at
      the step of measurement after the forceps are aligned on the polyp. DESIGN: This
      was a prospective assessment of 49 gastroenterologists who received training on
      10 photographs of polyps with aligned forceps and then measured 10 additional
      test polyps from photographs. One of the test photographs was excluded because of
      incorrect forceps alignment. SETTING: Data analyzed at an academic medical
      center. INTERVENTION: Photographs displayed in a webinar. MAIN OUTCOME
      MEASUREMENTS: Description of rates of accurate measurements, including the
      fraction correct within 50% and 25% margins of error. RESULTS: A total of 37% of
      all measurements were correct to the exact millimeter, 34% were larger, and 29%
      smaller compared with the reference standard. A total of 47 of 49 doctors
      measured all 9 polyps within 50% of the reference standard, and 21 measured all 9
      correctly within a 25% error margin. LIMITATIONS: Other potential sources of
      error in open forceps measurement were not evaluated. CONCLUSION: Open forceps
      polyp size determination is subject to error at the step of using the fully
      aligned forceps as a scale for measurement. A margin of error of 50% up or down
      is needed to prevent this step in size determination from causing errors in polyp
      matching in clinical trials comparing diagnosis-only imaging to colonoscopy.

PMID- 24119507
TI  - Increased mortality with peptic ulcer bleeding in patients with both compensated
      and decompensated cirrhosis.
AB  - BACKGROUND: Cirrhosis is associated with worse outcomes in peptic ulcer bleeding
      (PUB). There are no population-based studies from the United States on the impact
      of cirrhosis on PUB outcomes. OBJECTIVE: To investigate the impact of cirrhosis
      on outcomes of patients with PUB. DESIGN: Cross-sectional study. SETTING:
      Nationwide Inpatient Sample 2009. PATIENTS: International Classification of
      Diseases, the 9th revision, codes were used to identify patients with PUB and
      cirrhosis. The control group was patients with PUB without cirrhosis. MAIN
      OUTCOME MEASUREMENTS: In-hospital mortality, length of stay, and hospitalization
      costs. RESULTS: A total of 96,887 discharges with PUB as a diagnosis were
      identified-3574 with PUB and cirrhosis and 93,313 with PUB alone without
      cirrhosis. Mortality of PUB with concomitant cirrhosis was higher than in the
      control group without cirrhosis (5.5% vs 2%; P = .01); decompensated cirrhosis
      had higher mortality than did compensated cirrhosis (6.6% vs 3.9%; P = .01). In
      multivariate analysis, the presence of cirrhosis independently increased
      mortality (adjusted odds ratio (aOR) 3.3; 95% confidence interval [CI], 2.2-4.9).
      Stratified analysis showed that decompensated cirrhosis (aOR 4.4; 95% CI, 2.6
      7.3) had higher mortality than compensated cirrhosis (aOR 1.9; 95% CI, 1.04-3.6).
      There was no difference in the proportion of patients who underwent endoscopy
      within 24 hours (51.9% vs 51.1%; P = .68) between those with cirrhosis and
      controls. Patients with cirrhosis received less surgical intervention (aOR 0.8;
      95% CI, 0.6-0.9) compared with controls. Hospitalization costs also were
      increased in patients with decompensated cirrhosis. LIMITATIONS: Administrative
      data set. CONCLUSION: Both decompensated and compensated cirrhosis are associated
      with increased mortality in patients with PUB.

PMID- 24119508
TI  - Efficiency of endocytoscopy in differentiating types of serrated polyps.
AB  - BACKGROUND: Accurate endoscopic criteria are needed to differentiate serrated
      polyps, including hyperplastic polyp (HP), sessile serrated adenoma/polyp
      (SSA/P), and traditional serrated adenoma (TSA), because some are precursors of
      colorectal cancers. OBJECTIVE: To determine the endocytoscopic features of each
      type of serrated polyp, especially the shapes of lumens and nuclei. DESIGN:
      Retrospective study. SETTING: Single, tertiary-care referral center. PATIENTS:
      Patients who underwent removal of serrated polyps from May 2005 to December 2012.
      INTERVENTION: Endocytoscopy was performed. Endocytoscopic images were evaluated
      by assessing the shapes of the lumens and nuclei of the target lesions. MAIN
      OUTCOME MEASUREMENTS: The significant endocytoscopic features in differentiating
      among types of serrated polyps. RESULTS: Of the 58 eligible lesions, 27 were
      classified as HP, 12 as SSA/P, and 19 as TSA. Most HPs (77.8%) had star-like
      lumens, and most SSA/Ps (83.3%) had oval lumens. The lumens of TSAs were serrated
      (31.6%) or villous (68.4%), with both shapes seen only in TSAs. Most HPs (92.6%)
      and SSA/Ps (75.0%) had small, round nuclei, and all TSAs had fusiform nuclei.
      Features significantly differentiating TSAs from HPs and SSA/Ps were the presence
      of fusiform nuclei (P < .001) and villous (P < .001) and serrated (P = .002)
      lumens. The presence of oval lumens was significantly characteristic of SSA/Ps (P
      < .001), and the presence of star-like lumens was significantly characteristic of
      HPs (P < .001). LIMITATIONS: Retrospective design. Single-center study.
      CONCLUSION: The shape of lumens and nuclei on endocytoscopy can efficiently
      differentiate among the different types of serrated polyps. ( CLINICAL TRIAL
      REGISTRATION NUMBER: UMIN Clinical Trials Registry UMIN000007850.).

PMID- 24119509
TI  - Wireless capsule endoscopy.
AB  - Over the last decade, WCE has established itself as a valuable test for imaging
      the small intestine. It is a safe and relatively easy procedure to perform that
      can provide valuable information in the diagnosis of small-bowel conditions. Its
      applications still remain limited within the esophagus and colon. Future
      developments may include improving visualization within the esophagus and
      developing technologies that may allow manipulation of the capsule within the GI
      tract and biopsy capabilities.

PMID- 24119510
TI  - Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over
      the past 25 years: a population-based study.
AB  - BACKGROUND: Comprehensive, population-based data on ERCP use over the last 30
      years in North America are lacking. OBJECTIVE: To establish crude and age
      adjusted population-based rates of ERCP, evaluate for changing indications for
      ERCP, and evaluate for interactions between cholecystectomy technique and ERCP
      use from 1984 to 2009. DESIGN: Retrospective, comprehensive, population-based
      study. SETTING: All inpatient and outpatient ERCPs and cholecystectomies in
      Manitoba, Canada from 1984 to 2009. PATIENTS: All residents of Manitoba, Canada
      with a history of ERCP and/or cholecystectomy. INTERVENTION: None. MAIN OUTCOME
      MEASUREMENTS: Yearly crude and age-adjusted rates of ERCP (diagnostic and
      therapeutic) and cholecystectomy (open, laparoscopic, and with open bile duct
      exploration), and patient and/or procedure demographics. RESULTS: The rate of
      ERCP/10,000 people increased from 7.70 (1984) to 13.86/10,000 (2009) (P = .001).
      Diagnostic ERCP declined from 7.28/10,000 (1984) to 1.11/10,000 (2009), and
      therapeutic ERCP increased from 0.42/10,000 (1984) to 12.75/10,000 (2009) (P <
      .001). ERCPs were more common in women (62%) and in older populations (60-79
      years, >80 years), with rates of therapeutic ERCP reaching 62.58/10,000 in the
      elderly. The primary indication for ERCP has changed over time, with biliary
      indications increasing from 50.3% to 67.3% and pancreatic indications decreasing
      from 18.3% to 8.1% (P < .05). The rate of therapeutic ERCP increased during the
      transition from open to laparoscopic cholecystectomy (1991-1994), whereas open
      bile duct exploration (OBDE) decreased from 2.0 to 0.18/10,000 (P < .001).
      LIMITATIONS: Retrospective analysis, administrative data. CONCLUSION: ERCP use
      increased steadily from 1984 to 2009, and changed from a diagnostic modality to a
      therapeutic one. Changes in cholecystectomy technique may have influenced
      therapeutic ERCP use and likewise, the availability of therapeutic ERCP has
      decreased the need for OBDE.

PMID- 24119511
TI  - Reducing wasteful innovation.

PMID- 24119512
TI  - The impact of the financial crisis on the quality of care in primary care: an
      issue that requires prompt attention.

PMID- 24119513
TI  - Gender differences in cardiovascular disease risk management for Pacific
      Islanders in primary care.
AB  - OBJECTIVES: To assess gender differences in cardiovascular disease risk (CVR)
      assessment and management for Pacific people in New Zealand. METHODS: New Zealand
      guidelines indicate CVR assessment from age 35 years for Pacific men and from age
      45 years for Pacific women. Using general practice electronic medical records
      from 16 practices in New Zealand, the rate of CVR screening, treatment patterns
      and physiological measures for high-CVR (>=15% five-year) patients were assessed
      for Pacific patients >=20 years of age by gender. RESULTS: Records for 10 863
      Pacific patients showed a higher proportion of indicated women screened for CVR
      (65 vs 56%), but a lower proportion of assessed women with high CVR (28% for
      Pacific women vs 40% for Pacific men). Many of these high-CVR patients had
      physiological measures well above desirable levels based on their most recent
      readings. In the high-CVR group, women had similar CVR levels to men, but higher
      systolic blood pressure and HbA1c level, and a higher proportion of women were
      treated with antihypertensive and oral antidiabetic medication. There were
      substantial levels of poor medication adherence, particularly for cholesterol
      lowering medication. Women and men were equally likely to adhere to treatment.
      Those adhering to relevant medications had lower blood pressure, total-to-HDL
      cholesterol ratio and HbA1c than non-adherers. CONCLUSIONS: Pacific men were less
      likely than Pacific women to have their CVR assessed when indicated, more likely
      once assessed to have high CVR and equally likely to adhere to treatment.
      Medication adherence was associated with better control of risk factors and
      should be further promoted in this population.

PMID- 24119514
TI  - Convergence of HbA1c values towards target in 272 primary care patients following
      nine years of target-driven care.
AB  - BACKGROUND: We wished to determine the effect of a target-driven incentivised
      programme on haemoglobin A1c (HbA1c ) values in a UK diabetic population.
      METHODS: An audit was carried out in 1999-2000, which included an estimation of
      glycaemic control in a randomly selected diabetic cohort from ten primary care
      practices in Sutton Coldfield, serving a population of 90 000 patients. Each
      practice was given a randomised list of patients and asked to complete detailed
      questionnaires on patients with confirmed diabetes. We collected data on 516
      patients, 425 of whom had their HbA1c measured in 1999-2000 (Audit 2000). A re
      audit of HbA1c was carried out in 2007-08 (Audit 2008) determining the changes in
      HbA1c since the original audit. Of the original cohort, 272 patients had an audit
      of HbA1c carried out in Audit 2008. RESULTS: Overall, a small increase in median
      and mean HbA1c values was observed. We estimated that the proportion of patients
      with HbA1c achieving the lower Quality and Outcomes Framework HbA1c target of <
      7.5%; 173 of the 272 patients met this target in Audit 2000, whereas the number
      was 162 in Audit 2008. To understand the changes observed, patients were
      stratified as quintiles based on the HbA1c in Audit 2000 and changes in HbA1c
      after 8 years for each quintile were estimated. The mean changes for the
      different quintiles are: quintile 1 (HbA1c < 6.1%), +1.49%; quintile 2 (HbA1c 6.1
      6.6%), +0.8%; quintile 3 (HbA1c 6.7-7.3%), +0.3%; quintile 4 (HbA1c 7.4-8.5%), 
      0.18%; and quintile 5 (HbA1c > 8.5%), -1.55%. CONCLUSION: Our results suggest
      that, eight years on, patients with poor glycaemic control in 2000 saw an overall
      decrease in HbA1c by 2008, with the reverse seen in patients with good control.

PMID- 24119515
TI  - Measuring for improvement.
AB  - This is the fourth in a series of articles about the science of quality
      improvement. We examine what to measure, how to measure and some important
      measurement techniques, such as run charts, control charts and funnel plots.
      These help us to understand healthcare processes, to assess whether they are
      stable or improving and to determine how they can be improved further. 

PMID- 24119516
TI  - The patient liaison officer: a new role in UK general practice.
AB  - BACKGROUND: The population health needs of an ageing population, with increasing
      demands and opportunities for intervention, mean that the National Health Service
      (NHS) in the United Kingdom (UK) faces inevitable change. Maintaining traditional
      boundaries and professional roles is placing an unmanageable burden on the NHS
      and its workforce. Redesigning roles and developing capacity for integrated
      working across traditional boundaries of primary and secondary may provide ways
      of sustaining the health service whilst involving patients and carers in a
      community care model. AIMS: This project explores development of a patient
      liaison officer (PLO) in general practice to support delivery of integrated
      community care for patients with complex health needs and long-term conditions.
      It seeks to improve communication and administrative functions between different
      care providers, and incorporate patient and carer voices in care planning and
      delivery. It supports the UK national agenda for increasing care in the community
      and identifies learning needs for this new workforce. It provides career
      development opportunities for existing medical receptionists with potential to
      reduce administrative work for general practitioners (GPs). METHOD: A new role in
      general practice was developed through discussion and formal training based on
      identified key competencies of a liaison officer. Based in Bromley Clinical
      Commissioning Group (CCG) in South London, UK, 39 of 46 possible practices were
      involved. Outcome measures included: the development of a new role; the design
      and implementation of training, and evaluation of the participant; and teacher
      and observer feedback, including post-training focus groups, using thematic
      analysis. RESULTS AND CONCLUSIONS: Positive uptake and feedback indicated
      significant potential for developing this role. Investment in implementation may
      facilitate the achievement of improvements in healthcare and new Quality and
      Outcomes Framework (QOF) targets through better co-ordinated care. Future
      evaluation will include patient surveys and measures of impact on avoidable
      hospitalisation for vulnerable patients, and GP feedback on whether time has been
      released for new clinical work through reduction in administration carried out by
      PLOs.

PMID- 24119517
TI  - A comprehensive model for diagnosing the causes of individual medical performance
      problems: skills, knowledge, internal, past and external factors (SKIPE).
AB  - This discussion paper describes a new and comprehensive model for diagnosing the
      causes of individual medical performance problems: SKIPE (skills, knowledge,
      internal, past and external factors). This builds on a previous paper describing
      a unifying theory of clinical practice, the RDM-p model, which captures the
      primary skill sets required for effective medical performance (relationship,
      diagnostics and management), and the professionalism that needs to underpin them.
      The SKIPE model is currently being used, in conjunction with the RDM-p model, for
      the in-depth assessment and management of doctors whose performance is a cause
      for concern. 

PMID- 24119519
TI  - Image quality: it really does matter.

PMID- 24119520
TI  - Elective neck dissection versus observation for cN0 neck of squamous cell
      carcinoma primarily located in the maxillary gingiva and alveolar ridge: a
      retrospective study of 129 cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the results of elective neck
      dissection (END) versus those of observation in the treatment of squamous cell
      carcinoma of the maxillary gingiva. STUDY DESIGN: This was a retrospective study
      of 129 cases. RESULTS: There were 2 (4.0%) patients in the END group and 19
      (24.1%) patients in the observation group who developed nodal recurrence alone.
      The regional recurrence rate of the observation group was 9.1% for T1 disease,
      19.0% for T2, 27.3% for T3, and 40.0% for T4. Patients with stages T2 to T4 who
      underwent END received more survival benefit than did those in the observation
      group (P = .048). There were no statistical differences for patients with stage
      T1 disease between the 2 groups (P = .605). CONCLUSIONS: This retrospective study
      suggests that END should be recommended as a preferred management strategy for
      stage T2 to T4 disease and that observation may be an acceptable alternative to
      END for stage T1 tumors if strict compliance with a cancer surveillance protocol
      is followed.

PMID- 24119518
TI  - Interleukin-6 directly impairs the erythroid development of human TF-1
      erythroleukemic cells.
AB  - Anemia of inflammation or chronic disease is a highly prevalent form of anemia.
      The inflammatory cytokine interleukin-6 (IL-6) negatively correlates with
      hemoglobin concentration in many disease states. The IL-6-hepcidin antimicrobial
      peptide axis promotes iron-restricted anemia; however the full role of IL-6 in
      anemia of inflammation is not well-defined. We previously reported that chronic
      inflammation had a negative impact on maturation of erythroid progenitors in a
      mouse model. We hypothesized that IL-6 may be responsible for impaired
      erythropoiesis, independent of iron restriction. To test the hypothesis we
      utilized the human erythroleukemia TF-1 cell line to model erythroid maturation
      and exposed them to varying doses of IL-6 over six days. At 10 ng/ml, IL-6
      significantly repressed erythropoietin-dependent TF-1 erythroid maturation. While
      IL-6 did not decrease the expression of genes associated with hemoglobin
      synthesis, we observed impaired hemoglobin synthesis as demonstrated by decreased
      benzidine staining. We also observed that IL-6 down regulated expression of the
      gene SLC4a1 which is expressed late in erythropoiesis. Those findings suggested
      that IL-6-dependent inhibition of hemoglobin synthesis might occur. We
      investigated the impact of IL-6 on mitochondria. IL-6 decreased the mitochondrial
      membrane potential at all treatment doses, and significantly decreased
      mitochondrial mass at the highest dose. Our studies indicate that IL-6 may impair
      mitochondrial function in maturing erythroid cells resulting in impaired
      hemoglobin production and erythroid maturation. Our findings may indicate a novel
      pathway of action for IL-6 in the anemia of inflammation, and draw attention to
      the potential for new therapeutic targets that affect late erythroid development.

PMID- 24119521
TI  - Double-blind, randomized, controlled clinical trial of the effects of diosmectite
      and basic fibroblast growth factor paste on the treatment of minor recurrent
      aphthous stomatitis.
AB  - OBJECTIVE: This study investigated the effectiveness and safety of topical
      application of diosmectite (DS) and basic fibroblast growth factor (bFGF) paste
      in the treatment of minor recurrent aphthous stomatitis. STUDY DESIGN: Four
      pastes, containing bFGF and DS, DS alone, bFGF alone, and vehicle only, were
      consecutively applied 4 times per day for 5 days. Pain levels and the amount of
      ulcer amelioration were evaluated. RESULTS: A total of 129 participants completed
      the study. DS+bFGF paste released bFGF continuously and significantly lowered
      ulcer pain scores (P < .05 for days 3, 4, 5, and 6) compared with the other
      pastes. The ulcer size was significantly reduced (P < .05 for days 2, 4, and 6)
      in the DS+bFGF paste group compared with the other groups. No obvious adverse
      drug effects were observed. CONCLUSIONS: DS+bFGF paste was effective in
      alleviating ulcer pain and promoting healing without significant side effects in
      the treatment of minor recurrent aphthous stomatitis.

PMID- 24119522
TI  - Oral mucosal immunity.
AB  - Oral keratinocytes and dendritic cells of the oral mucosa, through molecular
      pattern recognition receptors, distinguish between commensal and pathogenic
      microorganisms and mediate the generation of protective immunoinflammatory
      responses to potentially invading pathogens or mediate immune tolerance toward
      commensal microorganisms. Oral immune tolerance is the result either of lack of
      activation of T cells in response to immunogenic presentation of antigens or of
      suppression of activity of effector T cells by regulatory T cells. Secretory
      immunoglobulin A (sIgA) antibodies at oral mucosal sites contribute to oral
      immunity by limiting colonization of microorganisms and their invasion of the
      epithelium. Ig isotype class switching to IgA is either dependent on or
      independent of T helper cells and is facilitated by cytokines secreted by
      dendritic cells and monocytes. 

PMID- 24119524
TI  - Immunoglobulin heavy chain gene rearrangement in oral B cell lymphomas.
AB  - OBJECTIVE: Oral non-Hodgkin lymphomas (NHLs) are an extensive group of malignant
      lymphoid cell neoplasms that are the second most common group of oral cancers.
      Subtyping NHL is important to plan for appropriate treatment, and the analysis of
      clonality is in many instances used for helping in the diagnosis of NHL. Thus,
      the aim of this study was to analyze immunoglobulin heavy chain (IgH) gene
      rearrangement in a series of oral B cell lymphomas to investigate the sensitivity
      of seminested polymerase chain reaction (snPCR). STUDY DESIGN: Paraffin embedded
      tissue samples from 16 cases of oral B cell lymphomas were retrieved and
      subjected to snPCR to investigate the IgH gene rearrangement. RESULTS: The
      results showed monoclonal IgH rearrangement in 85.7% of the cases studied, as
      represented by finding one band within the expected range of amplification.
      CONCLUSIONS: This study found that snPCR is a consistent method for the detection
      of gene rearrangement in paraffin-embedded tissue.

PMID- 24119523
TI  - Efficacy of intralesional betamethasone for erosive oral lichen planus and
      evaluation of recurrence: a randomized, controlled trial.
AB  - OBJECTIVE: This study aimed to determine the efficacy and safety of intralesional
      betamethasone in erosive oral lichen planus and to evaluate relapse of erosion.
      STUDY DESIGN: Patients were randomly assigned to the experimental group (1.4 mg
      intralesional betamethasone) or to the control group (8 mg intralesional
      triamcinolone acetonide), and they received injections once a week for 2 weeks.
      Erosive area and pain level were assessed on days 1, 7 +/- 2, and 14 +/- 2. If
      the lesion disappeared, any recurrence within the following 3 months was
      recorded. RESULTS: Twenty-nine participants in the experimental group and 30 in
      the control group completed the protocol. Healed percentage was higher with
      betamethasone (93.1%) than with triamcinolone (66.7%; P = .02), and final
      reduction in erosion area was greater in the experimental group (21.276 +/-
      21.064 mm(2)) than in the control group (11.5 +/- 12.95 mm(2); P = .02).
      Reduction in pain level did not differ between groups. The proportion of
      participants with recurrent erosions was significantly lower in the experimental
      group (14.8%) than in the control group (45%; P = .04). CONCLUSIONS:
      Intralesional betamethasone may be used in the topical treatment of erosive oral
      lichen planus.

PMID- 24119525
TI  - TGIF1 splicing variant 8 is overexpressed in oral squamous cell carcinoma and is
      related to pathologic and clinical behavior.
AB  - OBJECTIVE: Possible differences in splicing variants of TGIF1 in oral squamous
      cell carcinoma (OSCC) have not yet been reported. This study analyzed the
      expression levels of different splicing variants of the TGIF1 gene in OSCC
      compared with nontumoral epithelium (NT) and the relationship with clinical
      pathologic features of tumors. STUDY DESIGN: Forty-eight frozen samples of OSCC
      and 17 of NT were analyzed using quantitative reverse transcription polymerase
      chain reaction. RESULTS: TGIF1v2 and v8 are overexpressed in OSCC, whereas
      TGIF1v5 is underexpressed when compared with NT. Low TGIF1v8 expression was
      correlated with lower cellular differentiation, positive blood vascular invasion,
      advanced pathologic stage, and positive vascular lymphatic invasion of OSCC.
      TGIF1v8 is also related to overall survival over time, with lower values
      associated with an increased risk of cancer-related death. CONCLUSIONS: These
      data suggest that alternative splicing of TGIF1 is deregulated in OSCC, with
      overexpression of some splicing variants, especially TGIF1v8, which is associated
      with advanced stages of OSCC.

PMID- 24119526
TI  - Location dependency of the spatial resolution of cone beam computed tomography
      for dental use.
AB  - OBJECTIVE: This study evaluates the spatial resolution of cone beam computed
      tomography for dental use (CBCT) via modulation transfer function (MTF) analyses.
      STUDY DESIGN: Two models of CBCT system, 3DX FPD8 and FineCube v.12, were used.
      MTF analysis was applied to each CBCT system using a thin tungsten wire
      technique. RESULTS: The MTF curves in the radial direction on the XY-plane were
      concordant regardless of position, whereas the curves in the azimuthal direction
      tended to decrease as the distance from the rotation center increased. In the Z
      axis direction, the MTF curve of the medial level of the field of view was
      superior to that of any other level. CONCLUSION: The spatial resolution of CBCT
      systems depends on the location within the field of view. Because the spatial
      resolution was the highest in the medial level and rotation center position, an
      object should be placed at this position during a CBCT examination.

PMID- 24119527
TI  - Contact allergy masquerading as seronegative Sjogren's syndrome.
AB  - Primary Sjogren's syndrome is an autoimmune disease that presents with xerostomia
      and keratoconjunctivitis sicca (due to chronic lymphocytic inflammation of the
      salivary and lacrimal glands) and in some cases extraglandular features. Patients
      typically have positive antinuclear, anti-Ro, and anti-La antibodies; however,
      around 20% to 30% do not and are therefore termed seronegative. We present a case
      of a 58-year-old woman who was originally diagnosed with seronegative Sjogren's
      syndrome based on the American-European classification system. She had complete
      resolution of her clinical features on identification and avoidance of relevant
      contact allergens. Contact allergy should be considered in the differential
      diagnosis of seronegative Sjogren's syndrome, especially where atypical features
      such as facial rash, normal salivary gland imaging, or lichenoid histology exist.

PMID- 24119528
TI  - What constitutes a proper routine oral cancer examination for patients at low
      risk? Findings from a Delphi survey.
AB  - OBJECTIVE: A Delphi survey was used to develop a consensus opinion regarding what
      should constitute a routine oral cancer examination performed by general dentists
      when examining patients at low risk for oral cancer. STUDY DESIGN: This Delphi
      survey consisted of 5 rounds and used, as the expert panel, a stratified national
      sample of academically based US oral surgeons, oral pathologists, and oral
      medicine specialists, that is, the persons who teach the identification and
      diagnosis of oral cancer to all future general practitioners. RESULTS: After
      defining the population at low risk for oral cancer and the examination frequency
      in rounds 1 and 2, in rounds 3 to 5 the panelists evaluated and debated 28
      proposed examination elements. They reached consensus agreement to include 25 of
      those elements and to exclude 2 of them, but the panel did not achieve consensus
      on the remaining element. CONCLUSION: The panel reached consensus agreement on 25
      recommended elements for an annual examination of patients at low risk for oral
      cancer.

PMID- 24119529
TI  - Melorheostosis and central giant cell granuloma of the mandible in a 15-year-old
      girl.
AB  - Melorheostosis is a nonhereditary bone dysplasia primarily affecting the
      appendicular skeleton. Because clinical and histologic features are often
      nonspecific, the diagnosis is often based on the radiographic presentation.
      Involvement of the craniofacial skeleton is rare. We describe a case of a 15-year
      old girl with appendicular and craniofacial melorheostosis with adjacent central
      giant cell granuloma. We discuss the possible significance of this previously
      unreported finding. 

PMID- 24119530
TI  - Isolation of thermophilic L-lactic acid producing bacteria showing homo
      fermentative manner under high aeration condition.
AB  - By applying non-sterile open fermentation of food waste, various thermotolerant l
      lactic acid-producing bacteria were isolated and identified. The predominant
      bacterial isolates showing higher accumulation of l-lactic acid belong to 3
      groups of Bacillus coagulans, according to their 16S rRNA gene sequence
      similarities. B. coagulans strains M21 and M36 produced high amounts of l-lactic
      acid of high optical purity and lactic acid selectivity in model kitchen refuse
      medium and glucose-yeast extract-peptone medium. Other thermotolerant isolates
      resembling to Bacillus humi, B. ruris, B. subtilis, B. niacini and B. soli were
      also identified. These bacteria produced low amounts of l-lactic acid of more
      than 99% optical purity. All isolated strains showed the highest growth rate at
      temperatures around 55-60 degrees C. They showed unique responses to various
      oxygen supply conditions. The majority of isolates produced l-lactic acid at a
      low overall oxygen transfer coefficient (KLa); however, acetic acid was produced
      instead of l-lactic acid at a high KLa. B. coagulans M21 was the only strain that
      produced high, consistent, and reproducible amounts of optically pure l-lactic
      acid (>99% optical purity) under high and low KLa conditions in a homo
      fermentative manner.

PMID- 24119531
TI  - Environmental, personal, and behavioral factors are related to body mass index in
      a group of multi-ethnic, low-income women.
AB  - Environmental, personal, and behavioral determinants of body mass index (BMI) are
      not well understood in the low-income demographic. To investigate these factors,
      a cross-sectional survey was developed using Social Cognitive Theory (SCT),
      utilizing formative data from focus groups and measured environmental, personal,
      and behavioral constructs, in addition to food-related self-identity, food
      security, and heights and weights. Participants were urban women (n=330) who
      qualified for a food and nutrition assistance program. Data collection occurred
      at sites within the community, including homeless shelters, food pantries,
      libraries, and community centers. The outcome of interest was BMI and the
      relationship to environmental, personal, and behavioral constructs, and food
      related self-identity. All three SCT construct models were significant, but the
      personal construct regression model predicted the greatest variance in BMI among
      the women (31%). Decreased BMI was associated with SCT and self-identity
      variables indicating preventative behaviors, while increased BMI was associated
      with SCT and self-identity emotional eating variables. Overall results suggest
      that personal, behavioral, and self-identity factors can help to explain some
      weight variation observed among women living in similar obesogenic, low-income
      environments. Although additional research is needed, results suggest
      interventions with this population should address eating healthy to prevent
      disease, exercising for health, and shaping health-promoting self-identities. 

PMID- 24119532
TI  - Nutrient intakes among children and adolescents eating usual pizza products in
      school lunch compared with pizza meeting HealthierUS School Challenge criteria.
AB  - Pizza is a popular food that can contribute to high intakes of saturated fat and
      sodium among children and adolescents. The objective of this study was to compare
      daily nutrient intakes when a pizza product meeting the US Department of
      Agriculture's criteria for competitive food entrees under the HealthierUS School
      Challenge (HUSSC) was substituted for usual pizza products consumed during
      foodservice-prepared school lunch. The study used National Health and Nutrition
      Examination Survey (2005-2008) dietary recall data from a cross-sectional sample
      of US children and adolescents (age 5 to 18 years, n=337) who ate pizza during
      school lunch on 1 day of dietary recall. Daily nutrient intakes based on the
      consumption of usual pizza products for school lunch (pre-modeled) were compared
      with intakes modeled by substituting nutrient values from an HUSSC whole-grain
      pizza product (post-modeled). Paired t tests were used to make the comparison.
      Post-modeled intakes were lower in daily energy, carbohydrate, total fat,
      saturated fat, cholesterol, and sodium compared with pre-modeled intakes among
      children and adolescents (P<0.01). Protein, dietary fiber, vitamin A, and
      potassium intakes were higher in the post-modeled intake condition compared with
      the pre-modeled condition (P<0.01). Substituting the healthier pizza product for
      usual pizza products may significantly improve dietary quality of children and
      adolescents eating pizza for school lunch, indicating that it could be an
      effective approach to improve the nutritional quality of school lunch programs. 

PMID- 24119534
TI  - Effects of neck pain on reaching overhead and reading: a case-control study of
      long and short neck flexion.
AB  - BACKGROUND: Reaching overhead and reading are tasks that many individuals
      encounter daily. The level of difficulty of these tasks increases if an
      individual has neck pain. This study determined the neck movement patterns during
      these two tasks by comparing neck flexion of individuals with and without neck
      pain. METHODS: This case control study used the portable video technology,
      Dartfish ProSuite 5.5 Video Software, to analyse neck flexion movement patterns.
      Healthy individuals and individuals with neck pain were videotaped while they
      completed two tasks: reaching overhead from a standing position and reading from
      a sitting position. A single position of interest was selected for analysis from
      both tasks. The degree of neck flexion presented by the participant in this
      position at the beginning and end of the task was recorded. The angle change
      between these two time points was calculated for each participant. Differences
      between groups were determined by comparing the average flexion angle changes in
      groups by t-tests. RESULTS: The average angle change experienced by controls and
      neck pain participants during the overhead reaching tasks were very similar and a
      significant difference was not observed. The average angle changes experienced by
      the two groups during the reading task were more variable, but not significantly
      different. A t-test comparing average neck flexion angle change during dominant
      arm elevation for controls (m = -5.28, sd = 31.14) and neck pain participants (m
      = 5.07, sd = 32.41) revealed a mean between group difference of -10.34 (t17 = 
      0.688, p = 0.5003). The average neck flexion angle change during long neck
      flexion was not statistically different between controls (m = 10.08, sd = 18.89)
      and neck pain participants (m = 4, sd = 18.18); although the mean between group
      difference was 6.08 (t17 = 0.6856, p = 0.5022). CONCLUSIONS: Task performance is
      highly variable between individuals making it difficult to assess the impact of
      neck pain on small samples even with detailed motion analysis. Despite this,
      there was a difference in neck posture during reaching activities between
      controls and patients with neck pain. Neck pain can therefore influence the
      movement patterns used during daily activities. This has implications for primary
      and secondary prevention.

PMID- 24119533
TI  - Community resource utilization, psychosocial health, and sociodemographic factors
      associated with diet and physical activity among low-income obese Latino
      immigrants.
AB  - Low-socioeconomic-status (SES) Latinos are disproportionately represented among
      the 78 million obese Americans. Tailored behavioral weight-loss interventions
      show promise, but there is limited adaptation to lower-SES Latino immigrants.
      This study provides guidance for tailoring obesity-reduction strategies for this
      population by evaluating food security, educational community resource
      utilization, education level, depression, sex, and length of US residence as
      predictors of diet and physical activity. The cross-sectional study used baseline
      data collected in July 2009 through September 2010 for a weight-loss trial among
      lower-SES obese (body mass index 30 to 55) Latino immigrants who were enrolled at
      a community health clinic (n=207). Physical activity was measured using 7-day
      pedometer recording. Dietary intake was measured using an interviewer
      administered food frequency questionnaire. Factors assessed by questionnaire
      included education community resource use (nutrition and physical activity
      classes), education level, US residence (years), food security, and depressive
      symptoms. Data were analyzed using multivariate-adjusted linear regression
      models. More than one third of participants were sedentary (<5,000 steps/day),
      and 41% had low fruit and vegetable intake (<5 servings/day). In multivariate
      adjusted models, educational community resource use, male sex, less education,
      fewer depressive symptoms, and shorter US residence time were associated with
      more physical activity (all, P <= 0.05). Educational community resource use was
      positively associated with fruit and vegetable intake (P=0.05). Male sex was
      associated with more sweet-beverage intake (P=0.02) and fast-food intake
      (P=0.04). Fewer depressive symptoms were associated with lower sweet-beverage
      intake (P=0.05). In conclusion, obesity-reduction strategies among low-SES Latino
      immigrants might effectively emphasize educational community resource use and
      interventions tailored for psychosocial and sociodemographic characteristics.

PMID- 24119535
TI  - NMDA receptor encephalitis: late treatment also effective.

PMID- 24119536
TI  - Transcript level of nucleostemin in newly diagnosed acute myeloid leukemia
      patients.
AB  - To clarify the role of nucleostemin (NS) in AML, its transcription levels in bone
      marrow (BM) samples obtained from 128 newly diagnosed AML patients were analyzed.
      We determined that the highest NS transcription level was in M1 patients, while
      the lowest NS transcription level was in M3 patients. NS mRNA expression is
      positively correlated with blast percentages (%) and CD34, CD117 and CD123
      antigen expression in BM samples but is unrelated to the transcription level of
      WT1. A significant difference in NS expression between poor-risk and better-risk
      and between poor-risk and intermediate-risk AML patients was found. Our initial
      data indicated that NS can be used for tracking minimal residual disease (MRD)
      and is a helpful guide for treatment.

PMID- 24119537
TI  - Improvement in health and empowerment of families as a result of watershed
      management in a tribal area in India - a qualitative study.
AB  - BACKGROUND: Tribal people in India, as in other parts of the world, reside mostly
      in forests and/or hilly terrains. Water scarcity and health problems related to
      it are their prime concern. Watershed management can contribute to resolve their
      health related problems and can put them on a path of socio-economic development.
      Integrated management of land, water and biomass resources within a watershed,
      i.e. in an area or a region which contributes rainfall water to a river or lake,
      is referred to as watershed management. Watershed management includes soil and
      water conservation to create water resources, management of drinking water,
      improving hygiene and sanitation, plantation of trees, improving agriculture,
      formation of self-help groups and proper utilisation and management of available
      natural resources. For successful implementation of such a solution,
      understanding of perceptions of the tribal community members with regard to
      public health and socioeconomic implications of watershed management is
      essential. METHODS: A qualitative study with six focus group discussions (FGDs),
      three each separately for men and women, was conducted among tribal community
      members of the Maharashtra state of India. The data collected from the FGDs were
      analyzed using manifest and latent content analysis. RESULTS: "Improvement in
      health and empowerment of families as a result of watershed management" was
      identified as the main theme. Participants perceived that their health problems
      and socio-economic development are directly and/or indirectly dependent upon
      water availability. They further perceived that watershed management could
      directly or indirectly result in reduction of their public health related
      challenges like waterborne diseases, seasonal migration, alcoholism, intimate
      partner violence, as well as drudgery of women and may enhance overall
      empowerment of families through agricultural development. CONCLUSIONS: Tribal
      people perceived that water scarcity is the main reason for their physical,
      mental and social health problems and a major obstacle for their overall
      development. The perceptions of tribal participants indicate that infectious
      diseases, migration, alcoholism, intimate partner violence and drudgery of women
      are end results of water scarcity and efforts to increase water availability
      through watershed management may help them to achieve their right to health which
      is embedded in their right to access to water.

PMID- 24119539
TI  - Defensin-based anti-infective strategies.
AB  - Cationic and amphiphilic peptides are widely distributed in eukaryotic organisms
      and constitute a first line of host defense against invading pathogens. Some of
      these host defense peptides (HDPs) combine specific antibiotic activities with
      modulation of immune responses. Moreover, they are active against bacteria
      resistant to conventional antibiotics and show only modest resistance development
      under in vitro selection pressure. Based on these features, HDPs and particularly
      defensins are considered a promising source of novel anti-infective agents. This
      review summarizes the current knowledge about defensins from different kingdoms
      and discusses their potential for therapeutic application. 

PMID- 24119538
TI  - Human enterovirus 71 epidemics: what's next?
AB  - Human enterovirus 71 (EV71) epidemics have affected various countries in the past
      40 years. EV71 commonly causes hand, foot and mouth disease (HFMD) in children,
      but can result in neurological and cardiorespiratory complications in severe
      cases. Genotypic changes of EV71 have been observed in different places over
      time, with the emergence of novel genotypes or subgenotypes giving rise to
      serious outbreaks. Since the late 1990s, intra- and inter-typic recombination
      events in EV71 have been increasingly reported in the Asia-Pacific region. In
      particular, 'double-recombinant' EV71 strains belonging to a novel genotype D
      have been predominant in mainland China and Hong Kong over the last decade,
      though co-circulating with a minority of other EV71 subgenotypes and coxsackie A
      viruses. Continuous surveillance and genome studies are important to detect
      potential novel mutants or recombinants in the near future. Rapid and sensitive
      molecular detection of EV71 is of paramount importance in anticipating and
      combating EV71 outbreaks. 

PMID- 24119540
TI  - Epidermin and gallidermin: Staphylococcal lantibiotics.
AB  - The Staphylococcus epidermidis derived epidermin was the first lantibiotic that
      has been shown to be ribosomally synthesized and posttranslationally modified.
      Together with gallidermin, produced by Staphylococcus gallinarum, they belong to
      the large class of cationic antimicrobial peptides (CAMPs) that act against a
      broad spectrum of Gram-positive bacteria. Here we describe the genetic
      organization, biosynthesis and modification, excretion, extracellular activation
      of the modified pre-peptide by proteolytic processing, self-protection of the
      producer, gene regulation, structure, and the mode of action of gallidermin and
      epidermin. We also address mechanisms of bacterial tolerance to these
      lantibiotics and other CAMPs. Particularly gallidermin has a high potential for
      therapeutic application, as it is active against methicillin-resistant
      Staphylococcus aureus strains (MRSA) and as it is able to prevent biofilm
      formation at sublethal concentrations. 

PMID- 24119541
TI  - Abnormal mineral metabolism and mortality in hemodialysis patients with secondary
      hyperparathyroidism: evidence from marginal structural models used to adjust for
      time-dependent confounding.
AB  - BACKGROUND: Hemodialysis patients with mineral and bone disorders (MBDs) have an
      abnormally high relative risk of death, but their absolute risk of death is
      unknown. Further, previous studies have not accounted for possible time-dependent
      confounding of the association between MBD markers and death due to the effect of
      markers of MBD on treatments, which subsequently may affect MBD markers. STUDY
      DESIGN: Multicenter, 3-year, prospective, case-cohort study. SETTING &
      PARTICIPANTS: 8,229 hemodialysis patients with secondary hyperparathyroidism
      (parathyroid hormone level >=180 pg/mL and/or receiving vitamin D receptor
      activators) at 86 facilities in Japan. PREDICTORS: Serum phosphorus, calcium, and
      parathyroid hormone levels. OUTCOME: All-cause mortality. MEASUREMENTS: Marginal
      structural models were used to compute absolute differences in all-cause
      mortality associated with different levels of predictors while accounting for
      time-dependent confounding. RESULTS: The association between phosphorus level and
      mortality appeared U-shaped, although only higher phosphorus level categories
      reached statistical significance: compared to those with phosphorus levels of 5.0
      5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (>=9.0 mg/dL [>=2.90
      mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio,
      2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest
      phosphorus category (<3.0 mg/dL [<0.97 mmol/L]; rate ratio, 1.54 [95% CI, 0.87
      2.71]). Similarly, hypercalcemia (>=10.0 mg/dL [>=2.50 mmol/L]) was associated
      with excess deaths, and the highest level of hypercalcemia (>=11.0 mg/dL [>=2.75
      mmol/L]) was associated with 5.8 excess deaths/100 person-years (rate ratio, 2.38
      [95% CI, 1.77-3.21]) compared to those with levels of 9.0-9.4 mg/dL (2.25-2.37
      mmol/L). Abnormally high parathyroid hormone levels were not associated with
      excess deaths. LIMITATIONS: Possible residual confounding. CONCLUSIONS: These
      results reinforce the idea that serum calcium (in addition to phosphorus) level
      is an important predictor of the absolute risk of death in hemodialysis patients
      with secondary hyperparathyroidism.

PMID- 24119542
TI  - Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease
      and frontotemporal dementia.
AB  - Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease,
      can cause frontotemporal dementia (FTD). Moreover, a rare TREM2 exon 2 variant
      (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an
      odds ratio as strong as that for APOEepsilon4. We systematically screened the
      TREM2 coding region within a Belgian study on neurodegenerative brain diseases
      (1216 AD patients, 357 FTD patients, and 1094 controls). We observed an
      enrichment of rare variants across TREM2 in both AD and FTD patients compared to
      controls, most notably in the extracellular IgV-set domain (relative risk = 3.84
      [95% confidence interval = 1.29-11.44]; p = 0.009 for AD; relative risk = 6.19
      [95% confidence interval = 1.86-20.61]; p = 0.0007 for FTD). None of the rare
      variants individually reached significant association, but the frequency of
      p.R47H was increased ~ 3-fold in both AD and FTD patients compared to controls,
      in line with previous reports. Meta-analysis including 11 previously screened AD
      cohorts confirmed the association of p.R47H with AD (p = 2.93*10(-17)). Our data
      corroborate and extend previous findings to include an increased frequency of
      rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants
      may play a role in neurodegenerative diseases in general.

PMID- 24119543
TI  - Apolipoprotein E genotype influences spatial distribution of cerebral
      microbleeds.
AB  - In cerebral amyloid angiopathy patients, microbleeds often cluster, mostly
      occipital, and are associated with apolipoprotein E (APOE) genotype. Microbleeds
      also frequently occur in the asymptomatic, general population. In this
      population, we investigated spatial distribution of microbleeds and whether this
      is influenced by APOE genotype. In 292 persons with microbleeds, we labeled
      microbleeds on baseline and follow-up magnetic resonance images. We calculated
      distance between incident and prevalent microbleeds within and between persons
      and performed lobar segmentation on the magnetic resonance images. Subsequently,
      we investigated proximity and lobar distribution in strata of APOE genotype.
      Microbleeds occurred closer within persons than between persons (-42.2 mm, 95%
      confidence interval, -44.6 to -39.9; p < 0.001). Microbleeds within APOE epsilon2
      and epsilon4 carriers occurred closer than those in persons with epsilon3epsilon3
      genotype (-11.9 mm, 95% confidence interval, -24.4 to 0.6; p = 0.06). Persons
      with epsilon2 and epsilon4 alleles had a larger proportion of microbleeds in the
      occipital lobe than persons with epsilon3epsilon3 genotype. Similar to cerebral
      amyloid angiopathy patients, microbleeds in the general population cluster and
      the distribution is affected by APOE genotype.

PMID- 24119544
TI  - Aging affects medial but not anterior frontal learning-related theta
      oscillations.
AB  - Aging induces a decline in the ties that bind anatomical networks centered on the
      prefrontal cortex, which are critical for reinforcement learning and decision
      making. At the neurophysiological level, the prefrontal cortex may engage
      electrophysiological oscillatory synchronization to coordinate other brain
      systems during learning. We recorded scalp EEG from 21 older (mean age 69 years)
      and 20 young (mean age 22 years) healthy human adults while they learned stimulus
      response mappings by trial-and-error using feedback. In young adults, theta-band
      (4-8 Hz) oscillatory power over medial frontal and anterior frontal cortex
      predicted learning after errors. Older adults demonstrated a decrease in the
      theta-band learning-predictive signals over medial frontal but not anterior
      frontal cortex. This age-related decrease in task-relevant medial frontal theta
      power may be related to the more general decrease in medial frontal theta power
      that we observed during rest. These results demonstrate a shift in cortical
      networks that support reinforcement learning in older adults, and shed new light
      on the changes in neurophysiological (oscillatory) mechanisms with neurocognitive
      aging. 

PMID- 24119545
TI  - hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem
      proteinopathy" and frontotemporal lobar degeneration phenotypes.
AB  - hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing
      in three families presenting with multisystem proteinopathy (MSP), a rare complex
      phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of
      bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis
      (ALS). No study has evaluated the exact frequency of these genes in cohorts of
      MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP
      phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations
      could be implicated in the pathogenesis of these disorders. No disease-causing
      mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are
      rare in MSP and FTLD spectrum of diseases, although further investigations in
      larger populations are needed. 

PMID- 24119547
TI  - Executive dysfunction and gray matter atrophy in amnestic mild cognitive
      impairment.
AB  - Recent studies have shown that impairment in executive function (EF) is common in
      patients with amnestic mild cognitive impairment (aMCI). However, the
      neuroanatomic basis of executive impairment in patients with aMCI remains
      unclear. In this study, multiple regression voxel-based morphometry analyses were
      used to examine the relationship between regional gray matter volumes and EF
      performance in 50 patients with aMCI and 48 healthy age-matched controls. The
      core EF components (response inhibition, working memory and task switching, based
      on the EF model of Miyake et al) were accessed with computerized tasks. Atrophic
      brain areas related to decreases in the three EF components in patients with aMCI
      were located in the frontal and temporal cortices. Within the frontal cortex, the
      brain region related to response inhibition was identified in the right inferior
      frontal gyrus. Brain regions related to working memory were located in the left
      anterior cingulate gyrus, left premotor cortex, and right inferior frontal gyrus,
      and brain regions related to task shifting were distributed in the bilateral
      frontal cortex. Atrophy in the right inferior frontal gyrus was most closely
      associated with a decrease in all three EF components in patients with aMCI. Our
      data, from the perspective of brain morphology, contribute to a better
      understanding of the role of these brain areas in the neural network of EF. 

PMID- 24119546
TI  - Choosing Alzheimer's disease prevention clinical trial populations.
AB  - To assist investigators in making design choices, we modeled Alzheimer's disease
      prevention clinical trials. We used longitudinal Clinical Dementia Rating Scale
      Sum of Boxes data, retention rates, and the proportions of trial-eligible
      cognitively normal participants age 65 and older in the National Alzheimer's
      Coordinating Center Uniform Data Set to model trial sample sizes, the numbers
      needed to enroll to account for drop out, and the numbers needed to screen to
      successfully complete enrollment. We examined how enrichment strategies affected
      each component of the model. Relative to trials enrolling 65-year-old
      individuals, trials enriching for older (minimum 70 or 75) age required reduced
      sample sizes, numbers needed to enroll, and numbers needed to screen. Enriching
      for subjective memory complaints reduced sample sizes and numbers needed to
      enroll more than age enrichment, but increased the number needed to screen. We
      conclude that Alzheimer's disease prevention trials can enroll elderly
      participants with minimal effect on trial retention and that enriching for older
      individuals with memory complaints might afford efficient trial designs. 

PMID- 24119548
TI  - Bouveret's syndrome on FDG PET/CT: a rare life-threatening complication of
      gallstone disease.

PMID- 24119549
TI  - (18)F-FDG PET/CT findings in a case with HIV (-) Kaposi sarcoma.
AB  - Although mucocutaneous sites are the most frequently encountered sites of
      involvement, Kaposi Sarcoma (KS) may also occasionally involve the breast and the
      skeletal, endocrine, urinary and nervous systems.. Various imaging modalities may
      be used to delineate the extent of the disease by detecting unexpected sites of
      involvement. Herein, we report a case of classical type KS, in whom staging with
      (18)F-FDG PET/CT imaging disclosed widespread disease and unexpected findings of
      bone and salivary gland involvement.

PMID- 24119550
TI  - [Detection of tumors in the central zone of the prostate with 11C-Choline
      PET/CT].
AB  - Prostate tumors originate 68% in the peripheral region and 24% in the
      transitional region where tumors originating in the central zone are rare (8%).
      However, diagnosis of the tumors in the central zone is important since they
      exhibit greater aggressiveness conditioned by their location and different
      biological behavior. Magnetic resonance imaging shows problems in identifying
      lesions in the central prostate zone, since this region has a heterogeneous
      signal, mainly after the primary treatment. Ultrasound guided sextant biopsy
      shows a negative result in 28% of prostate tumors. Therefore, it is advisable to
      repeat or even to perform saturation biopsies. We present two patients, one of
      them with suspected biochemical prostate cancer and one with biochemical
      recurrence after radical treatment. In both, (11)C-Choline PET/CT allowed
      detection of the tumor focus in the central zone of the prostate, with negative
      complementary diagnostic test and biopsies. 

PMID- 24119551
TI  - Intratumoral genetic heterogeneity in metastatic melanoma is accompanied by
      variation in malignant behaviors.
AB  - BACKGROUND: Intratumoral heterogeneity is a major obstacle for the treatment of
      cancer, as the presence of even minor populations that are insensitive to therapy
      can lead to disease relapse. Increased clonal diversity has been correlated with
      a poor prognosis for cancer patients, and we therefore examined genetic,
      transcriptional, and functional diversity in metastatic melanoma. METHODS:
      Amplicon sequencing and SNP microarrays were used to profile somatic mutations
      and DNA copy number changes in multiple regions from metastatic lesions. Clonal
      genetic and transcriptional heterogeneity was also assessed in single cell clones
      from early passage cell lines, which were then subjected to clonogenicity and
      drug sensitivity assays. RESULTS: MAPK pathway and tumor suppressor mutations
      were identified in all regions of the melanoma metastases analyzed. In contrast,
      we identified copy number abnormalities present in only some regions in addition
      to homogeneously present changes, suggesting ongoing genetic evolution following
      metastatic spread. Copy number heterogeneity from a tumor was represented in
      matched cell line clones, which also varied in their clonogenicity and drug
      sensitivity. Minor clones were identified based on dissimilarity to the parental
      cell line, and these clones were the most clonogenic and least sensitive to
      drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for
      drug-resistant cells resulted in the adoption of a gene expression profile with
      features of one of the minor clones, supporting the idea that these populations
      can mediate disease relapse. CONCLUSION: Our results support the hypothesis that
      minor clones might have major consequences for patient outcomes in melanoma.

PMID- 24119552
TI  - Evaluation of ergonomic and education interventions to reduce occupational
      sitting in office-based university workers: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Prolonged sitting is a specific occupational hazard in office
      workers. There is growing evidence that prolonged sitting is detrimental to
      metabolic health. The aim of this study is to determine whether providing office
      workers with education along with adjustable sit-stand workstations leads to
      reduction in sitting behavior. METHODS/DESIGN: A randomized control trial (RCT)
      with three groups (one control group and two intervention groups) will be
      conducted in an office workplace setting. The education intervention group will
      receive an education package that encourages reduction in sitting behaviors. The
      sit-stand desk intervention group will receive the same education package along
      with an adjustable sit-stand desk. Participants will be included in the study if
      they are currently employed in a full-time academic or administrative role that
      involves greater than 15 hours per week or greater than 4 hours per day computer
      based work. Baseline data will include participant's age, gender, weight, height,
      smoking habit, employment position, level of education, and baseline self
      reported leisure time physical activity. The primary outcome is the average daily
      sedentary time during work hours, measured by an accelerometer. Participant
      recruitment commenced in March 2013 and will be completed by December 2013.
      DISCUSSION: This study will determine whether providing office workers with an
      adjustable sit-stand desk and individually targeted education, or education
      alone, is more effective in decreasing sitting behaviors than no intervention.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12613000366752.

PMID- 24119553
TI  - Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series.
AB  - A series of novel quinolinone-chalcone hybrids and analogues were designed,
      synthesized and their biological activity against the mammalian stages of
      Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular
      scaffolds with significant microbicidal activity and low cytotoxicity were
      identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against
      both organisms, being the most potent anti-L. infantum agent of the entire series
      (IC50 value of 1.3+/-0.1 MUM). Compounds 4 and 11 showed potency toward the
      intracellular, amastigote stage of L. infantum (IC50 values of 2.1+/-0.6 and
      3.1+/-1.05 MUM, respectively). Promising trypanocidal compounds include 5 and 10
      (IC50 values of 2.6+/-0.1 and 3.3+/-0.1 MUM, respectively) as well as 6 and 9
      (both having IC50 values of <5 MUM). Chemical modifications on the quinolinone
      chalcone scaffold were performed on selected compounds in order to investigate
      the influence of these structural features on antiparasitic activity.

PMID- 24119554
TI  - GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR
      and evaluation of a prodrug strategy for oral efficacy in pain models.
AB  - The synthesis and structure-activity relationship of decahydroisoquinoline
      derivatives with various benzoic acid substitutions as GluK1 antagonists are
      described. Potent and selective antagonists were selected for a tailored prodrug
      approach in order to facilitate the evaluation of the new compounds in pain
      models after oral administration. Several diester prodrugs allowed for acceptable
      amino acid exposure and moderate efficacy in vivo. 

PMID- 24119555
TI  - Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic
      acids bearing urea/thiourea unit as potent histone deacetylase inhibitors.
AB  - A novel class of di-substituted cinnamic hydroxamic acid derivatives containing
      urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors.
      All tested compounds demonstrated significant HDAC inhibitory activities and anti
      proliferative effects against diverse human tumor cell lines. Among them, 7l
      exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM.
      It also showed strong cellular inhibition against diverse cell lines including
      HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and
      0.48 MUM, respectively.

PMID- 24119556
TI  - Synthesis and biological evaluation of technetium-99m labeled galactose
      derivatives as potential asialoglycoprotein receptor probes in a hepatic fibrosis
      mouse model.
AB  - Two galactose derivatives, a monovalent (99m)Tc-MAMA-MGal galactoside and a
      divalent (99m)Tc-MAMA-DGal galactoside, were synthesized and radiolabeled in high
      radiochemical purity (>98%). Dynamic microSPECT imaging and biodistribution study
      of two traces in normal and liver fibrosis mice showed that the (99m)Tc-MAMA-DGal
      revealed higher specific binding to asialoglycoprotein receptors in liver and
      then rapidly excreted via both hepatobiliary system and renal clearance. The
      results suggest that (99m)Tc-MAMA-DGal may be used as SPECT probes for
      noninvasive evaluation of asialoglycoprotein receptor-related liver dysfunction. 

PMID- 24119557
TI  - 3-[2-(Aminomethyl)-5-[(pyridin-4-yl)carbamoyl]phenyl] benzoates as soft ROCK
      inhibitors.
AB  - Clinical development of ROCK inhibitors has so far been limited by systemic or
      local ROCK-associated side effects. A soft drug approach, which involves
      predictable metabolic inactivation of an active compound to a nontoxic
      metabolite, could represent an attractive way to obtain ROCK inhibitors with
      improved tolerability. We herein report the design and synthesis of a new series
      of soft ROCK inhibitors structurally related to the ROCK inhibitor Y-27632. These
      inhibitors contain carboxylic ester moieties which allow inactivation by
      esterases. While the parent esters display strong activity in enzymatic (ROCK2)
      and cellular (MLC phosphorylation) assays, their corresponding carboxylic acid
      metabolites have negligible functional activity. Compound 32 combined strong
      efficacy (ROCK2 IC50=2.5 nM) with rapid inactivation in plasma (t1/2 <5').
      Compound 32 also demonstrated in vivo efficacy when evaluated as an IOP-lowering
      agent in ocular normotensive New-Zealand White rabbits, without ocular side
      effects.

PMID- 24119558
TI  - Biological activity of 3-chloro-azetidin-2-one derivatives having interesting
      antiproliferative activity on human breast cancer cell lines.
AB  - Resveratrol (3,4',5 tri-hydroxystilbene), a natural plant polyphenol, has gained
      interest as a non-toxic agent capable of inducing tumor cell death in a variety
      of cancer types. However, therapeutic application of these beneficial effects
      remains very limited due to its short biological half-life, labile properties,
      rapid metabolism and elimination. Different studies were undertaken to obtain
      synthetic analogs of resveratrol with major bioavailability and anticancer
      activity. We have synthesized a series 3-chloro-azetidin-2-one derivatives, in
      which an azetidinone nucleus connects two aromatic rings. Aim of the present
      study was to investigate the effects of these new 3-chloro-azetidin-2-one
      resveratrol derivatives on human breast cancer cell lines proliferation. Our
      results indicate that some azetidin-based resveratrol derivatives may become new
      potent alternative tools for the treatment of human breast cancer. 

PMID- 24119559
TI  - Design, synthesis, and biological evaluation of bone-targeted proteasome
      inhibitors for multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and
      progressive bone destruction. Standard chemotherapeutic agents have not been
      effective at significantly prolonging the survival of MM patients and these
      agents are typically associated with often severe, dose-limiting side effects.
      There is great need for methods to target the delivery of novel, effective
      cytotoxic agents specifically to bone, where myeloma cells reside. We have
      synthesized and evaluated the effects of the bone-targeted proteasome inhibitors
      PS-341-BP-1, PS-341-BP-2 and MG-262-BP on cell proliferation using the mouse
      5TGM1 and human RPMI 8226 cell lines in vitro. The compounds exhibit strong
      cytotoxicity on MM cell lines and reduce the number of viable cells in a dose
      dependent manner. 

PMID- 24119560
TI  - Reply to: Jerry R. John, M.Ch. Respond to "microsurgery and limb salvage after
      electrical burn injury".

PMID- 24119561
TI  - Utility of alpha-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in
      distinguishing endometrial clear cell carcinomas from serous and endometrioid
      carcinomas.
AB  - The expression of alpha-methylacyl-coenzyme-A racemase (AMACR) has previously
      been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors
      that are known to display broad phenotypic overlap with their identically named
      mullerian counterparts. Herein, we assess the utility of AMACR in distinguishing
      endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas
      (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial
      carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were
      assessed for AMACR immunoreactivity, with results scored semiquantitatively
      (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells,
      respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the
      following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n =
      22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n
      = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in
      CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and
      specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95%
      confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively,
      with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve
      of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is
      strongly associated with CCC and displays a relatively robust diagnostic test
      performance. However, its practical utility may be limited by the focal nature of
      its expression in 32% of the AMACR-positive CCC cases as well as its expression
      in 15% to 22% of the non-CCC histotypes. 

PMID- 24119562
TI  - Distinct clinicopathologic characteristics of lung mucinous adenocarcinoma with
      KRAS mutation.
AB  - Primary mucinous adenocarcinomas are uncommon, and their pathogenesis remains
      unclear. We recently reported the clinicopathologic characteristics of surgically
      resected mucinous adenocarcinoma, including the frequent involvement of the left
      and lower lung and absence of central fibrosis. The present study attempted to
      clarify the pathogenesis of mucinous adenocarcinoma based on KRAS mutation
      status. We selected 45 mucinous adenocarcinoma cases from among 2474 surgically
      resected primary lung adenocarcinomas. Of these, 22 had a KRAS mutation (48.9%),
      whereas only 7 (15.6%) had an epidermal growth factor receptor mutation, and 2
      cases had both mutations. The mucinous adenocarcinomas with KRAS mutations were
      located in the lower lung lobe significantly more often (P < .05) than were
      tumors without KRAS mutation. The mucinous adenocarcinoma cases with KRAS
      mutations also had a significantly lower frequency of nuclear atypia (P < .05).
      We compared the degree of immunostaining for matrix metalloproteinase-7 (MMP-7),
      laminin-5, and geminin in the mucinous adenocarcinoma with and without KRAS
      mutation. The proportion of geminin-positive cells was lower among the cases with
      a mutation than among those without (0.7% versus 2.1%; P < .05). No significant
      differences in the extent of staining of the other markers were observed between
      the groups. The current study clearly demonstrated that mucinous adenocarcinomas
      with KRAS mutations have clinicopathologic characteristics different from those
      of mucinous adenocarcinoma without such mutations. 

PMID- 24119563
TI  - Small gastrointestinal stromal tumor in the stomach: identification of precursor
      for clinical gastrointestinal stromal tumor using c-kit and alpha-smooth muscle
      actin expression.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the digestive tract. To find precursors for clinical GISTs of the stomach, small
      gastric stromal tumors of less than 3 cm were collected and examined
      immunohistochemically with analysis of the KIT mutation. Sixty-eight of 74
      lesions were classified into 4 representative groups according to the expression
      of c-kit and alpha-smooth muscle actin (alphaSMA): group A, c-kit diffusely
      positive and alphaSMA negative (18 cases); group B, c-kit diffusely positive and
      alphaSMA focally positive (13); group C, c-kit focally positive and alphaSMA
      diffusely positive (27); and group D, c-kit negative and alphaSMA diffusely
      positive (10). Of the 4 groups, groups A and B of c-kit diffuse expression showed
      higher cellularity and labeling indices of p27(Kip1) and Ki-67 than did groups C
      and D of diffuse alphaSMA expression. Incidence of KIT exon 11 mutation in groups
      A and B was 86% (25/29), whereas that in groups C and D was 0% (0/20). Small
      gastric stromal tumors with c-kit diffuse expression were considered precursors
      for clinical GIST because they were significantly different from c-kit focally
      positive or negative tumors. The mutation of KIT is considered as an early event
      in tumorigenesis of GIST. 

PMID- 24119564
TI  - Surgical resection should be taken into consideration for the treatment of small
      gastric gastrointestinal stromal tumors.
AB  - BACKGROUND: The National Comprehensive Cancer Network (NCCN) recommends
      conservative follow-up for gastric gastrointestinal stromal tumors (GISTs) less
      than 2 cm. The aim of the present study was to investigate the clinical and
      pathological features of small gastric GISTs, re-evaluate the risk potential, and
      discuss the treatment strategy of small gastric GISTs. METHODS: In this
      retrospective study, 63 cases of small gastric GISTs (less than 2 cm) were
      resected surgically from May 2010 to March 2013 in our department.
      Clinicopathological factors were collected and the malignant potential of small
      gastric GISTs was analyzed. RESULTS: The mitotic index of 14 out of 63 cases
      (22.22%) exceeded 5. The malignant potential of small gastric GISTs was related
      to tumor location (P = 0.0218). The mitotic index of 4 out of 8 GISTs (50%)
      located in gastric cardia exceeded 5, 8 out 28 GISTs (28.57%) located in the
      gastric fundus exceeded 5, and only 2 out of 27 GISTs (7.41%) located in the
      gastric body exceeded 5. We also discovered a good consistency between mitotic
      index and Ki-67 expression of small gastric GISTs. CONCLUSIONS: Gastric GISTs
      less than 2 cm also have malignant potential. Thus, we recommended surgical
      resection of all small gastric GISTs once diagnosed.

PMID- 24119565
TI  - Streptogramins - two are better than one!
AB  - Streptogramins are potent drugs against numerous highly resistant pathogens and
      therefore are used as antibiotics of last-resort human therapy. They consist of a
      mixture of two different types of chemical substances - the group A
      streptogramins, which are polyunsaturated macrolactones, and the group B
      streptogramins, representing cyclic hexadepsipeptides. Streptogramins are unique
      in their mode of action: each component alone exhibits a moderate bacteriostatic
      activity by binding to the bacterial 50S ribosomal subunit and thereby blocking
      translation, whereas the synergic combination of both substances is up to hundred
      fold more effective than the single compounds, resulting in a bactericidal
      activity. The streptogramin biosynthetic genes are organized as large antibiotic
      superclusters. These clusters harbour numerous regulatory genes, which encode
      different types of regulators that together form a complex hierarchical
      signalling system, which governs the regulation of streptogramin biosynthesis.
      Resistance is also regulated by this cascade. However, whereas resistance against
      streptogramins is quite well understood in diverse pathogenic organisms, only
      little is known about how the natural producer strains protect themselves against
      these toxic compounds. Here, we give an overview about the recent advances in
      streptogramin investigations with a main focus on the best-studied
      representatives, pristinamycin and virginiamycin. We concentrate on the
      biosynthesis of these compounds, their regulation and resistance determinants as
      well as their application in medicine and food industry. 

PMID- 24119566
TI  - Bacterial caseinolytic proteases as novel targets for antibacterial treatment.
AB  - Bacterial Clp proteases are important for protein turnover and homeostasis in
      order to maintain vital cellular functions particularly under stress conditions.
      Apart from their crucial role in general protein quality control by degrading
      abnormally folded or otherwise aberrant or malfunctioning proteins, their
      temporally and spatially precise proteolysis of key regulatory proteins
      additionally guides several developmental processes like cell motility, genetic
      competence, cell differentiation, sporulation as well as important aspects of
      virulence. Due to their apparent relevance for many physiological processes and
      their conservation among diverse bacterial species including human pathogens, Clp
      proteases have attracted considerable attention as targets for antibacterial
      action in recent years. Particularly a novel class of potent acyldepsipeptide
      antibiotics unleashes ClpP, the uniform proteolytic core unit of the degradative
      Clp complexes, to bring about bacterial death via uncontrolled proteolysis of
      proteins that are essential for bacterial viability. In addition, covalent
      inhibition of the catalytic center of ClpP by another class of small molecule
      inhibitors is investigated in the context of virulence inhibition. Both
      antibacterial mechanisms constitute innovative approaches with the potential to
      control infections caused by multi-resistant bacterial pathogens due to the lack
      of cross-resistance to established antibiotic classes. 

PMID- 24119567
TI  - Future potential for anti-infectives from bacteria - how to exploit biodiversity
      and genomic potential.
AB  - The early stages of antibiotic development include the identification of novel
      hit compounds. Since actinomycetes and myxobacteria are still the most important
      natural sources of active metabolites, we provide an overview on these producers
      and discuss three of the most promising approaches toward finding novel anti
      infectives from microorganisms. These are defined as the use of biodiversity to
      find novel producers, the variation of culture conditions and induction of silent
      genes, and the exploitation of the genomic potential of producers via "genome
      mining". Challenges that exist beyond compound discovery are outlined in the last
      section. 

PMID- 24119568
TI  - Cyclic lipopeptides as antibacterial agents - potent antibiotic activity mediated
      by intriguing mode of actions.
AB  - Cyclic lipopeptides (CLPs) are a promising class of natural products with
      antibiotic properties. CLPs are amphiphilic molecules, composed of a fatty acid
      tail linked to a short oligopeptide which form a macrocylic ring structure. This
      review presents an overview of this class of antibiotics, focusing on the current
      and potential therapeutic applications and placing particular emphasis on the
      molecular modes of action of these compounds. 

PMID- 24119569
TI  - A new plant-derived antibacterial is an inhibitor of efflux pumps in
      Staphylococcus aureus.
AB  - An in-depth evaluation was undertaken of a new antibacterial natural product (1)
      recently isolated and characterised from the plant Hypericum olympicum L. cf.
      uniflorum. Minimum inhibitory concentrations (MICs) were determined for a panel
      of bacteria, including: meticillin-resistant and -susceptible strains of
      Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus
      haemolyticus; vancomycin-resistant and -susceptible Enterococcus faecalis and
      Enterococcus faecium; penicillin-resistant and -susceptible Streptococcus
      pneumoniae; group A streptococci (Streptococcus pyogenes); and Clostridium
      difficile. MICs were 2-8 mg/L for most staphylococci and all enterococci, but
      were >=16 mg/L for S. haemolyticus and were >32 mg/L for all species in the
      presence of blood. Compound 1 was also tested against Gram-negative bacteria,
      including Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica
      serovar Typhimurium but was inactive. The MIC for Mycobacterium bovis BCG was 60
      mg/L, and compound 1 inhibited the ATP-dependent Mycobacterium tuberculosis MurE
      ligase [50% inhibitory concentration (IC(50)) = 75 MUM]. In a radiometric
      accumulation assay with a strain of S. aureus overexpressing the NorA multidrug
      efflux pump, the presence of compound 1 increased accumulation of (14)C-enoxacin
      in a concentration-dependent manner, implying inhibition of efflux. Only moderate
      cytotoxicity was observed, with IC50 values of 12.5, 10.5 and 8.9 MUM against
      human breast, lung and fibroblast cell lines, respectively, highlighting the
      potential value of this chemotype as a new antibacterial agent and efflux pump
      inhibitor.

PMID- 24119570
TI  - Management of snakebite and systemic envenomation in rural Ecuador using the 20
      minute whole blood clotting test.
AB  - OBJECTIVES: In low-income countries, snakebites are frequently managed in rural
      areas in health centers with severely constrained resources. Many healthcare
      providers in these settings have limited access to the numerous and relatively
      expensive laboratory studies used to diagnose envenomation. The relatively simple
      and inexpensive 20-minute whole blood clotting test (WBCT) has been recommended
      by several international organizations for the diagnosis of certain venomous
      snakebites. This study proposes to confirm the utility of the WBCT as the sole
      laboratory diagnostic tool to determine systemic envenomation in hematotoxic
      snakebite management in severely resource-constrained areas of the world.
      METHODS: The authors reviewed all 110 cases of snakebite during a 6-year period
      in a small hospital in rural Ecuador using the WBCT. RESULTS: All cases presented
      within 24 hours of snakebite. Twenty cases revealed normal coagulation with no
      clinical evidence of systemic envenomation. Ninety cases had no evidence of clot
      formation (positive WBCT) at 20 minutes, suggesting systemic envenomation. Of
      these 90 cases, according to a classification scale, 54 were mild, 26 were
      moderate, and 10 were severe envenomations requiring transfer to tertiary care.
      All mild and moderate systemic envenomations were successfully treated at the
      rural hospital. All severe envenomations were treated initially with antivenom
      before transfer to tertiary care. One patient with severe envenomation died in
      tertiary care. CONCLUSIONS: The WBCT was predictive of the presence or absence of
      systemic envenomation from snakebite in our region. The WBCT guided the
      successful management of mild and moderate systemic envenomation, and spared
      patients with no evidence of systemic envenomation from potential side effects of
      antivenom.

PMID- 24119571
TI  - Exertional heat-related illnesses at the Grand Canyon National Park, 2004-2009.
AB  - BACKGROUND: The Grand Canyon National Park has approximately 4 million visitors
      between April and September each year. During this period, outdoor activity such
      as hiking is potentially hazardous owing to extreme heat, limited shade, and
      steep, long ascents. Given the high visitation and the public health interest in
      the effects of extreme heat, this study calculated morbidity rates and described
      heat-related illness (HRI) among visitors. METHODS: We conducted a retrospective
      cross-sectional study from April 1 through September 30, during 2004-2009. From a
      review of Ranger Emergency Medical Services (EMS) incident report files, we
      extracted information on those that met the case definition of greater than 1
      hour of outdoor heat exposure with an HRI assessment or diagnosis, HRI self
      report, or signs or symptoms of HRI without another etiology noted. Visitor and
      temperature data were obtained from respective official sources. RESULTS: Grand
      Canyon EMS responded to 474 nonfatal and 6 fatal HRI cases, with the majority
      (84%) being US residents, 29% from Western states. Of the nonfatal cases, 51%
      were women, the median age was 43 years (range, 11-83 years), and 18% reported a
      cardiovascular condition. Clinical HRI assessments included dehydration (25%),
      heat exhaustion (23%), and suspected hyponatremia (19%). Almost all (90%) were
      hiking; 40% required helicopter evacuation. The highest HRI rates were seen in
      May. CONCLUSIONS: HRI remains a public health concern at the Grand Canyon. High
      risk evacuations and life-threatening conditions were found. Majority were
      hikers, middle-aged adults, and US residents. These findings support the park's
      hiker HRI prevention efforts and use of park EMS data to measure HRI.

PMID- 24119572
TI  - Chemical and genetic diversity of Cremanthodium lineare.
AB  - Chemical constituents and evolutionally neutral DNA sequences of six samples of
      Cremanthodium lineare Maxim., collected in the Sichuan Province of China, were
      studied. Three samples produced furanoeremophilanes and the other three,
      eremophilan-8-ones. The chemotypes were found to be correlated with DNA sequence
      types, suggesting that the chemical diversity observed has a genetic origin.
      Production of furanoeremophilanes by a Cremanthodium species suggests an
      evolutionary relationship between Cremanthodium and Ligularia species, and
      possibly to related genera. 

PMID- 24119573
TI  - Role of equilibrative adenosine transporters and adenosine receptors as
      modulators of the human placental endothelium in gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is a diseases that alters human placenta
      macro and microvascular reactivity as a result of endothelial dysfunction. The
      human placenta is a highly vascularized organ which lacks innervation, so blood
      flux is governed by locally released vasoactive molecules, including the
      endogenous nucleoside adenosine and the free radical nitric oxide (NO). Altered
      adenosine metabolism and uptake by the endothelium leads to increased NO
      synthesis which then turns-off the expression of genes coding for a family of
      nucleoside membrane transporters belonging to equilibrative nucleoside
      transporters, particularly isoforms 1 (hENT1) and 2 (hENT2). This mechanism leads
      to increased extracellular adenosine and, as a consequence, activation of
      adenosine receptors to further sustain a tonic activation of NO synthesis. This
      is a phenomenon that seems operative in the placental macro and microvascular
      endothelium in GDM. We here summarize the findings available in the literature
      regarding these mechanisms in the human feto-placental circulation. This
      phenomenon is altered in the feto-placental vasculature, which could be crucial
      for understanding GDM deleterious effects in fetal growth and development. 

PMID- 24119574
TI  - Digital current regulator for proportional electro-hydraulic valves with unknown
      disturbance rejection.
AB  - Solenoid current regulation is well-known and standard in any proportional
      electro-hydraulic valve. The goal is to provide a wide-band transfer function
      from the reference to the measured current, thus making the solenoid a fast and
      ideal force actuator within the limits of the power supplier. The power supplier
      is usually a Pulse Width Modulation (PWM) amplifier fixing the voltage bound and
      the Nyquist frequency of the regulator. Typical analog regulators include three
      main terms: a feedforward channel, a proportional feedback channel and the
      electromotive force compensation. The latter compensation may be accomplished by
      integrative feedback. Here the problem is faced through a model-based design
      (Embedded Model Control), on the basis of a wide-band embedded model of the
      solenoid which includes the effect of eddy currents. To this end model parameters
      must be identified. The embedded model includes a stochastic disturbance dynamics
      capable of estimating and correcting the electromotive contribution together with
      parametric uncertainty, variability and state dependence. The embedded model
      which is fed by the measured current and the supplied voltage becomes a state
      predictor of the controllable and disturbance dynamics. The control law combines
      reference generator, state feedback and disturbance rejection to dispatch the PWM
      amplifier with the appropriate duty cycle. Modeling, identification and control
      design are outlined together with experimental result. Comparison with an
      existing analog regulator is also provided. 

PMID- 24119575
TI  - DGKzeta under stress conditions: "to be nuclear or cytoplasmic, that is the
      question".
AB  - Eukaryotic cells have evolved to possess a distinct subcellular compartment, the
      nucleus, separated from the cytoplasm in a manner that allows the precise
      operation of the chromatin, thereby permitting controlled access to the
      regulatory elements in the DNA for transcription and replication. In the
      cytoplasm, genetic information contained in the DNA sequence is translated into
      proteins, including enzymes that catalyze various reactions, such as metabolic
      processes, energy control, and responses to changing environments. One mechanism
      that regulates these events involves phosphoinositide turnover signaling, which
      generates a lipid second messenger, diacylglycerol (DG). Since DG acts as a
      potent activator of several signaling molecules, it should be tightly regulated
      to keep cellular responsiveness within a physiological range. DG kinase (DGK)
      metabolizes DG by phosphorylating it to generate phosphatidic acid, thus serving
      as a critical regulator of DG signaling. Phosphoinositide turnover is employed
      differentially in the nucleus and the cytoplasm. A member of the DGK family,
      DGKzeta, localizes to the nucleus in various cell types and is considered to
      regulate nuclear DG signaling. Recent studies have provided evidence that DGKzeta
      shuttles between the nucleus and the cytoplasm in neurons under
      pathophysiological conditions. Transport of a signal regulator between the
      nucleus and the cytoplasm should be a critical function for maintaining basic
      processes in the nucleus, such as cell cycle regulation and gene expression, and
      to ensure communication between nuclear processes and cytoplasmic functions. In
      this review, a series of studies on nucleocytoplasmic translocation of DGKzeta
      have been summarized, and the functional implications of this phenomenon in
      postmitotic neurons and cancer cells under stress conditions are discussed.

PMID- 24119577
TI  - [Annual Report 2011 REIN].

PMID- 24119576
TI  - Risk of developing severe sepsis after acute kidney injury: a population-based
      cohort study.
AB  - INTRODUCTION: Sepsis has been a factor of acute kidney injury (AKI); however,
      little is known about dialysis-requiring AKI and the risk of severe sepsis after
      survival to discharge. METHODS: We conducted a population-based cohort study
      based on the Taiwan National Health Insurance Research Database from 1999 to
      2009. We identified patients with AKI requiring dialysis during hospitalization
      and survived for at least 90 days after discharge, and matched them with those
      without AKI according to age, sex, and concurrent diabetes. The primary outcome
      was severe sepsis, defined as sepsis with a diagnosis of acute organ dysfunction.
      Individuals who recovered enough to survive without acute dialysis were further
      analyzed. RESULTS: We identified 2983 individuals (mean age, 62 years; median
      follow-up, 3.96 years) with dialysis-requiring AKI and 11,932 matched controls.
      The incidence rate of severe sepsis was 6.84 and 2.32 per 100 person-years among
      individuals with dialysis-requiring AKI and without AKI in the index
      hospitalization, respectively. Dialysis-requiring AKI patients had a higher risk
      of developing de novo severe sepsis than the non-AKI group. In subgroup analysis,
      even individuals with recovery from dialysis-requiring AKI were at high risk of
      developing severe sepsis. CONCLUSIONS: AKI is an independent risk factor for
      severe sepsis. Even patients who recovered from AKI had a high risk of long-term
      severe sepsis.

PMID- 24119578
TI  - [Survival and mortality in ESRD patients].
AB  - This chapter provides a set of indicators on survival, life expectancy and causes
      of death of patients in chronic renal failure treated by dialysis or
      transplantation beginning a first replacement therapy between 2002 and 2011. Age
      strongly influences survival on dialysis. Thus, one year survival of patients
      under age 65 is over 90%. After 5 years, among patients over 85 years, it is more
      than 15%. The presence of diabetes or one or more cardiovascular comorbidities
      also significantly worse patient survival. In terms of trend, we do not find
      significant improvement in the 2-year survival between patients in the cohort
      2006-2007 and the 2008-2009 cohort. Cardiovascular diseases account for 27% of
      causes of death to infectious diseases (12%) and cancer (10%). Life expectancy of
      patients is highly dependent on their treatment. Thus, a transplant patient aged
      30 has a life expectancy of 41 years versus 23 years for a dialysis patient.
      Transplant patients have a mortality rate much lower than those of dialysis
      patients. Thus, between 60 and 69 years, for 1000 patients in dialysis in 2011,
      127 died within the year. For 1000 patients of the same age, who have a
      functioning kidney transplant, 24 died within the year. 

PMID- 24119579
TI  - [Access to the waiting list and renal transplantation].
AB  - This chapter provides a set of indicators related to Renal Transplantation access
      in France. It describes patient outcomes and reports on cumulative incidence
      rates of wait-listing and renal transplantation according to main patient of
      characteristics and regions. The REIN registry integrates kidney transplant and
      dialysis data. It provides a comprehensive view on waiting list and renal
      transplantation access to the patients, nephrologists, and national or regional
      health authorities. Access to the waiting list is evaluated on a cohort of 51,845
      new patients who started dialysis between 2002 and 2011 in 25 regions. The
      probability of first wait-listing was of 3.7% at the start of dialysis (pre
      emptive registrations), 15% at 12, 22% at 36 and 24% to 60 months. The
      probability of being registered was strongly related to age, diabetes and region.
      Patient older than 60 had a very poor access to the waiting list, whatever their
      diabetes status was. Probability of first wait-listing was much lower (36.5% at
      60 months) in type 2 diabetic-40 to 59 years old patients. Among 13,653 patients
      less than 60 years old, the probability of being registered was 11% at the start
      of dialysis, 43% to 12 months, 62% to 36 months and 66% to 60 months (median
      dialysis duration: 16 months). Seventeen regions with up to 5 years follow-up
      show an increase of 8 to 15% in pre-emptive registrations between 2007 and 2001,
      without change at 1 year. Access to kidney transplant is evaluated on a cohort of
      53,301 new patients who started a renal replacement therapy (dialysis or pre
      emptive renal transplant) between 2002 and 2011 in 25 regions. The probability of
      first kidney transplant was of 7% at 12, 17% at 36 and 21% at 60 months. 8,633
      patients (16,2%) had received a first renal transplant within 14.7 month median
      time; 1,455 (2.7%) had received a pre-emptive graft [male: 58%, median age:
      48.7y]. Among the 14,770 new patients less than 60 years old, the probability of
      being transplanted was of 21% at 12, 46% at 36 and 58% at 60 months (median
      dialysis duration: 42 months). When pre-emptive graft were excluded, the
      probability of being transplanted was of 5% at 12, 15% to 36 and 19% to 60 months
      Insofar as kidney transplant is regarded as the most efficient treatment, access
      to the waiting list and renal transplant are sensitive issues. 

PMID- 24119580
TI  - [ESRD in children and adolescents].
AB  - This chapter provides indicators to describe the specificity of End Stage Renal
      Disease in children in France and to study these patients'outcome and the choices
      of treatment modalities. In 2011, the incidence and the prevalence of ESRD among
      patients under 20 years old remained stable at 8 and 53 pmp respectively. The
      first causes of ESDR remain uropathies and hypodysplasia followed by
      glomerulonephritis and genetic diseases. Considering the initial treatment, we
      found a high rate of hemodialysis and a low rate of peritoneal dialysis that is
      mainly used in younger children. In 2011, 31 preemptive transplantations were
      performed accounting for 27.7% of new patients. Finally, survival analysis
      confirm that younger children (under 4 years old) have the highest risk of death
      (88% survival rate at 2 years vs. 98% in patients over 4 years old) and that the
      treatment of choice remains the renal transplantation since it increases the
      expected remaining lifetime of 20 to 40 years depending on the considered age. 

PMID- 24119581
TI  - [Flows between modalities in the treatment of ESRD].
AB  - This chapter provides indicators to describe the outcome of prevalent and
      incident patients in the various modalities of treatment. Among the 36 849
      patients on dialysis at 31/10/2010, 79% were already on RRT at 31/12/2009.
      Respectively 91%, 85% and 93% of the patients on HD in-center, HD self-care unit
      and peritoneal dialysis were in the same modality of treatment the year before.
      Among the 29 758 patients with a functioning graft at 31/12/2010, 98% were
      already on RRT at 31/12/2009, 95% of them with a functioning graft. 72%, 72% and
      74% of the patients with in-center HD, outcenter HD and self-care unit were in
      the same modality of treatment at 31/12/2011. But 37% of the patients on PD at
      31/12/2010 were not on PD at 31/12/2011. In 2011, new patients represented 89% of
      the entries in peritoneal dialysis. Renal transplantation represented 10% of the
      outcomes of the HD patients in self-care unit or at home. 

PMID- 24119582
TI  - [The incidence of ESRD in 2011].
AB  - This chapter provides a set of indicators on incident patients with renal
      replacement therapy. In 2011, in 25 French regions (99% population), 9 248
      patients started a treatment by dialysis (incidence of dialysis: 149 per million
      inhabitants) and 334 patients with a pre-emptive graft without previous dialysis
      (incidence of pre-emptive graft: 5 per million inhabitants). One patient among
      two are over 70 years old at renal replacement therapy initiation. As in 2010,
      incidence rate seems to stabilize. 

PMID- 24119583
TI  - [Scientific production of REIN].

PMID- 24119584
TI  - [REIN Report 2011--summary].
AB  - INCIDENT PATIENTS: In 2011, in France, we estimate that 9 400 patients started a
      treatment by dialysis (incidence of dialysis: 144 per million inhabitants) and
      335 patients with a pre-emptive graft without previous dialysis (incidence of pre
      emptive graft: 5 per million inhabitants). As in 2010, incidence rate seems to
      stabilize. Elders provide the majority of new patients (median age at RRT start:
      71 years old). New patients present a high rate of disabilities especially
      diabetes (41% of the new patients) and cardiovascular disabilities (>50% of the
      new patients) that increase with age. Considering treatment and follow-up, the
      first treatment remains center's hemodialysis and we do not notice any
      progression of self-dialysis. RRT started in emergency in 33% of the patients.
      This finding contrasts with the fact that 56% of patients started hemodialysis on
      a catheter. This, together with the major inter-region variability, suggests that
      different strategies of management exist. Finally, the hemoglobin level at RRT
      start seems to be an interesting indicator of good management and follow-up since
      13% of patients presenting an underprovided follow-up have a hemoglobin level
      under 10g/dl, whereas only 2.5% of patients with an appropriate follow-up
      presented such a condition. PREVALENT PATIENTS: On December 31, 2011, in France,
      we estimate that 70.700 patients were receiving a renal replacement therapy,
      39.600 (56%) on dialysis and 31.100 (44%) living with a functional renal
      transplant. The overall crude prevalence was 1091 per million inhabitants. It was
      1.6 higher in males. Prevalence was subject to regional variations with 5 regions
      (3 overseas) above the national rate. Renal transplant share varied from 33% in
      Nord-Pas de Calais to 53% in Pays de Loire, and from 16 to 25% in overseas
      regions. The study of temporal variations for 18 regions contributing to the
      registry since 2007 demonstrated a +4% increase in standardized prevalence of
      ESRD patients with a functional transplant vs. +2% increase for dialysis,
      resulting in a decreasing gap between dialysis and transplantation prevalence,
      due to an increase number of renal transplant and a longer survival of
      transplanted patients. The main dialysis technique was hemodialysis (93.3% of
      patients). Even if an important inter-region variability remains considering the
      choices of treatment, more than 50% of the patients are undergoing hemodialysis
      in a hospital-based incenter unit, and we noticed an increase in hemodialysis in
      a medical satellite unit with time whereas the rate of self-care hemodialysis
      decreases. The rate of peritoneal dialysis remains stable. When comparing
      guidelines to real-life treatments, 77.5% of patients receive adequate dose of
      treatment (12 H/week, KT/ V>1.2), the rate of patients with a hemoglobin blood
      level lower than 10g/dl and without erythropoietin treatment is 1.3%, which
      confirmed a good management of anemia. On the contrary, 34% of patients have a
      BMI lower than 23kg/m(2) and only 23% have an albumin blood-level over 40g/l,
      which underlines that nutritional management of ESRD patients can be improved.
      MORTALITY: Age strongly influences survival on dialysis. Thus, one year survival
      of patients under age 65 is over 90%. After 5 years, among patients over 85
      years, it is more than 15%. The presence of diabetes or one or more
      cardiovascular comorbidities also significantly worse patient survival. In terms
      of trend, we do not find significant improvement in the 2-year survival between
      patients in the cohort 2006-2007 and the 2008-2009 cohort. Cardiovascular
      diseases account for 27% of causes of death to infectious diseases (12%) and
      cancer (10%). Life expectancy of patients is highly dependent on their treatment.
      Thus, a transplant patient aged 30 has a life expectancy of 41 years versus 23
      years for a dialysis patient. ESRD PEDIATRIC PATIENTS: In 2011, the incidence and
      the prevalence of ESRD among patients under 20 years old remained stable at 8 and
      53 per million inhabitants respectively. The first causes of ESDR remain
      uropathies and hypodysplasia followed by glomerulonephritis and genetic diseases.
      Considering the initial treatment, we found a high rate of hemodialysis and a low
      rate of peritoneal dialysis that is mainly used in younger children. In 2011, 31
      preemptive transplantations were performed accounting for 27.7% of new patients.
      Finally, survival analysis confirm that younger children (under 4 years old) have
      the highest risk of death (88% survival rate at 2 years vs. 98% in patients over
      4 years old) and that the treatment of choice remains the renal transplantation
      since it increases the expected remaining lifetime of 20 to 40 years depending on
      the considered age. TRANSPLANTATION: Access to the waiting list is evaluated on a
      cohort of 51,846 new patients who started dialysis between 2002 and 2011 in 25
      regions. The probability of first wait-listing was of 3.7% at the start of
      dialysis (pre-emptive registrations), 15% at 12, 22% at 36 and 24% to 60 months.
      Patient older than 60 had a very poor access to the waiting list, whatever their
      diabetes status was. Among 13,653 patients less than 60 years old, the
      probability of being registered was 11% at the start of dialysis, 43% to 12
      months, 62% to 36 months and 66% to 60 months (median dialysis duration: 16
      months). Seventeen regions with up to 5 years follow-up show an increase of 8 to
      15% in pre-emptive registrations between 2007 and 2001, without change at 1 year.
      Access to kidney transplant is evaluated on a cohort of 53,301 new patients who
      started a renal replacement therapy (dialysis or pre-emptive renal transplant)
      between 2002 and 2011 in 25 regions. The probability of first kidney transplant
      was of 7% at 12, 17% at 36 and 21% at 60 months. 8,633 patients (16,2%) had
      received a first renal transplant within 14.7 month median time; 1,455 (2.7%) had
      received a pre-emptive graft. Among the 14.770 new patients less than 60 years
      old, the probability of being transplanted was of 21% at 12, 46% at 36 and 58% at
      60 months (median dialysis duration: 42 months). When pre-emptive graft were
      excluded, the probability of being transplanted was of 5% at 12, 15% to 36 and
      19% to 60 months FLOW BETWEEN TREATMENT MODALITIES: Among the 36.849 patients on
      dialysis at 31/10/2010, 79% were already on RRT at 31/12/2009. Respectively 91%,
      85% and 93% of the patients on HD in-center, HD self-care unit and peritoneal
      dialysis were in the same modality of treatment the year before. Among the 29.758
      patients with a functioning graft at 31/12/2010, 98% were already on RRT at
      31/12/2009, 95% of them with a functioning graft.72%, 72% and 74% of the patients
      with in-center HD, out-center HD and self-care unit were in the same modality of
      treatment at 31/12/2011. But 37% of the patients on PD at 31/12/2010 were not on
      PD at 31/12/2011. In 2011, new patients represented 89% of the entries in
      peritoneal dialysis. Renal transplantation represented 10% of the outcomes of the
      HD patients in self-care unit or at home.

PMID- 24119585
TI  - [The prevalence of ESRD in 2011].
AB  - This chapter describes temporal and geographical variations of ESRD prevalence in
      France. This indicator assesses health needs of ESRD patients on dialysis or
      living with functional transplant. It does not include patients on conservative
      treatment. On December 31, 2011, 70 300 patients were receiving a renal
      replacement therapy in one of the 25 regions contributing to the registry, 39 200
      (56%) on dialysis and 31 100 (44%) living with a functional renal transplant. The
      overall crude prevalence was 1091pmh. It was 1.6 higher in males. Prevalence was
      subject to regional variations with 5 regions (3 overseas) above the national
      rate. Renal transplant share varied from 33% in Nord-Pas-de-Calais to 53% in Pays
      de Loire, and from 16 to 25% in overseas regions. The overall sex and age
      standardised prevalence was 40, 567 and 483 pmh respectively for peritoneal
      dialysis, haemodialysis and transplantation, with marked regional variations. The
      study of temporal variations for 18 regions contributing to the registry since
      2007 demonstrated a +4% increase in standardised prevalence of ESRD patients with
      a functional transplant vs +2% increase for dialysis, resulting in a decreasing
      gap between dialysis and transplantation prevalence, due to an increase number of
      renal transplant and a longer survival of transplanted patients. Such an
      evolution should prompt the nephrological community and health authorities to
      anticipate changes in the ESRD healthcare organisation and to adapt them to the
      regional context. 

PMID- 24119586
TI  - [Baseline characteristics and indicators of support for new dialysis patients in
      2011].
AB  - This chapter provides a set of indicators on incident patients starting renal
      replacement therapy (RRT) in France between the 1st of January 2011 and the
      31(st) of December 2011. Even if End-Stage Renal Disease can be found in all
      classes of ages, elders provide the majority of new patients (median age at RRT
      start: 71 years old). Those patients present a high rate of disabilities
      especially diabetes (41% of the new patients) and cardiovascular disabilities
      (>50% of the new patients) that increase with age. Considering treatment and
      follow-up, the first treatment remains center's hemodialysis and we do not notice
      any progression of self-dialysis. RRT started in emergency in 33% of the
      patients. This finding contrasts with the fact that 56% of patients started
      hemodialysis on a catheter. This, together with the major interregion
      variability, suggests that different strategies of management exist. Finally, the
      hemoglobin level at RRT start seems to be an interesting indicator of good
      management and follow-up since 13% of patients presenting an underprovided follow
      up have a hemoglobin level under 10g/dL, whereas only 2.5% of patients with an
      appropriate follow-up presented such a condition. 

PMID- 24119587
TI  - [The network].

PMID- 24119588
TI  - [Clinical characteristics and indicators of care of dialysis patients].
AB  - This chapter provides a set of indicators on patients treated by dialysis at
      December the 31th 2011. Even if ESRD is found in all classes of age, elders
      account for the great majority of the patients undergoing dialysis (median age:
      70.4 years). These patients present a high rate of comorbidity especially
      diabetes (37% of patients) and cardiovascular comorbidities (59% of patients)
      that increases with the patient's age. Considering indicators of care, the main
      dialysis technique was hemodialysis (93.3% of patients). Even if an important
      inter-region variability remains considering the choices of treatment, more than
      50% of the patients are undergoing hemodialysis in a hospital-based in-center
      unit, and we noticed an increase in hemodialysis in a medical satellite unit with
      time whereas the rate of self-care hemodialysis decreases. The rate of peritoneal
      dialysis remains stable. When comparing guidelines to real-life treatments, 77.5%
      of patients receive adequate dose of treatment (12H/week, KT/V>1.2), the rate of
      patients with a hemoglobin blood-level lower than 10 g/dl and without
      erythropoietin treatment is 1.3%, which confirmed a good management of anemia. On
      the contrary, 34% of patients have a BMI lower than 23 kg/m(2) and only 23% have
      an albumin blood-level over 40 g/l, which underlines that nutritional management
      of ESRD patients can be improved.

PMID- 24119589
TI  - Insulin detemir in the management of type 2 diabetes in non-Western countries:
      safety and effectiveness data from the A1chieve observational study.
AB  - AIMS: This subgroup analysis of the A1chieve study examined data from 15,545
      people who started treatment with insulin detemir +/- oral glucose-lowering drugs
      in routine clinical care. METHODS: A1chieve was a 24-week, international,
      prospective, non-interventional study of people with type 2 diabetes from non
      Western nations starting treatment with basal insulin detemir, bolus insulin
      aspart or biphasic insulin aspart 30, alone or in combination, to evaluate their
      safety and effectiveness in routine clinical practice. RESULTS: HbA1c for the
      global cohort improved after 24 weeks from 9.5 +/- 1.6% by -2.0 +/- 1.6% [80 +/-
      17 by -22 +/- 17 mmol/mol] (-2.1 +/- 1.6% [-23 +/- 17 mmol/mol] for insulin-naive
      participants; -1.6 +/- 1.7% [-17 +/- 19 mmol/mol] for prior insulin users).
      Fasting plasma glucose and postprandial plasma glucose were also significantly
      reduced (p<0.001), irrespective of prior therapy or geographical region. The
      incidence of major hypoglycaemia decreased significantly over 24 weeks in both
      the insulin-naive and insulin-experienced groups (p<0.0001). Mean body weight
      decreased overall by -0.4 +/- 4.0 kg and blood pressure, lipid profiles, and self
      reported quality of life improved over 24 weeks for all people starting treatment
      with insulin detemir. CONCLUSION: People with type 2 diabetes in poor glycaemic
      control starting treatment with insulin detemir reported significant improvements
      in glycaemic control with improved treatment tolerability, irrespective of prior
      treatment and geographical region, after 24 weeks.

PMID- 24119590
TI  - The effectiveness and safety of beginning insulin aspart together with basal
      insulin in people with type 2 diabetes in non-Western nations: results from the
      A1chieve observational study.
AB  - AIMS: The aim of this A1chieve sub-group analysis was to examine populations
      beginning insulin aspart together with any basal insulin, all +/- oral glucose
      lowering drugs: insulin aspart added to existing basal insulin (n=519); switched
      from biphasic insulin (n=947); switched from NPH plus human meal-time insulins
      (n=586); and insulin-naive begun with basal plus insulin aspart (n=1594).
      METHODS: A1chieve was a 24-week non-interventional study evaluating insulin
      analogues in 66,726 people with type 2 diabetes in routine clinical care in 28
      non-Western countries. Major endpoints were analysed as change from baseline
      using Student's paired t-test. RESULTS: Baseline glycaemic control was poor (mean
      HbA1c: 9.4-10.1% [79-87 mmol/mol]). HbA1c, FPG and PPPG improved significantly
      from baseline in all groups (mean change from baseline in HbA1c: -2.8 to -1.8% [
      31 to -20 mmol/mol]; FPG: -4.9 to -2.9 mmol/L; PPPG: -6.7 to -3.9 mmol/L; p<0.001
      for all), resulting in a similar level of blood glucose control for all groups at
      study end. Unsurprisingly, hypoglycaemia rates increased in those starting
      insulin, but decreased in the other groups. Clinically significant improvements
      in serum lipids and quality of life occurred across all groups. CONCLUSIONS:
      These data support the use of basal plus prandial insulin regimens in routine
      clinical practice in people with type 2 diabetes with inadequate glycaemic
      control.

PMID- 24119591
TI  - International Diabetes Federation.

PMID- 24119592
TI  - Accumulation of effector memory CD8+ T cells in nasal polyps.
AB  - BACKGROUND: T lymphocytes are prevalent in sinus mucosa and are implicated in
      chronic rhinosinusitis (CRS) pathogenesis. However, the major T-cell
      subpopulations, helper (CD4+) and cytotoxic (CD8+), have not been adequately
      examined in CRS. This study was designed to characterize human sinus mucosa and
      peripheral blood (PB) CD4+ and CD8+ T cells and their level of differentiation in
      CRS with nasal polyps (NPs), CRS without NPs, and control patients. METHODS: A
      prospective study was performed. Percentages of CD4+ and CD8+ T cells and their
      levels of differentiation were analyzed in sinus mucosa and PB by flow cytometry.
      Cell populations were defined as naive, central memory, effector memory, and
      effector T cells using cell surface markers CD45RA, CD62L, and CD27. The
      influence of coexisting allergy, sinus eosinophilic mucus (EM), and culture
      results were examined. RESULTS: In all patients, sinus mucosa had a lower
      percentage of CD4+ and a higher percentage of CD8+ T cells compared with PB.
      However, CRS with NPs (n = 86) had a significantly higher percentage of mucosal
      CD8+ T cells compared with CRS without NPs (n = 40) in control (n = 13) patients
      (p < 0.0001). Effector memory T cells were increased in sinuses compared with PB
      in all patients; however, the percentage of effector memory CD8+ T cells was
      greatest in CRS with NP mucosa (p = 0.002). Surprisingly coexisting allergy or
      culture results did not influence the mucosal T-cell phenotype. CRS with NP
      patients with sinus EM had a significantly higher percentage of mucosal CD8+ T
      cells. CONCLUSION: Sinus mucosa in CRS with NPs is characterized by a significant
      enrichment of CD8+ T cells and a relative deficiency of CD4+ T cells. The
      majority of NP CD8+ T cells had a terminally differentiated, mature, effector
      memory phenotype, which raises the question, whether these cells are pathogenic
      or appear as a consequence of inflammation, independent of the presence of
      allergy or positive microbial culture.

PMID- 24119593
TI  - Assessing the relationship between serum resistin and nasal obstruction in
      children with allergic rhinitis.
AB  - BACKGROUND: Nasal obstruction has been reported as a "key symptom" of allergic
      rhinitis (AR) because it is deeply associated with impaired quality of life and
      it reflects more directly the allergic inflammation in the nasal mucosa. Resistin
      is known to be involved in inflammatory processes exerting an important role in
      the regulation of cytokine production even though its effective proinflammatory
      activity at nasal level has never been fully established. This study investigates
      the relationship between resistin levels and nasal obstruction assessed by an
      objective method such as active anterior rhinomanometry. METHODS: Fifty-three
      children between 4 and 10 years of age affected by persistent allergic rhinitis
      (PAR) were enrolled and subdivided in two groups. Serum resistin levels were
      detected in all children. The same day patients underwent rhinomanometry, which
      was considered negative (no nasal obstruction) when the fraction of predicted
      values (p.v.'s) was between 71 and 100% and it was considered positive when the
      fraction of p.v. was <=70%. RESULTS: The serum resistin levels were significantly
      higher in children with moderate-severe PAR than in patients with mild PAR (p <
      0.03). Furthermore, serum resistin levels were significantly higher in children
      with positive rhinomanometry compared with negative rhinomanometry (p < 0.03).
      The fraction of p.v.'s of nasal flows in patients with nasal obstruction had a
      significant negative correlation with serum resistin levels (p < 0.001).
      CONCLUSION: This study provides evidence that resistin levels are increased in
      children with severe nasal obstruction measured by an objective and quantitative
      approach.

PMID- 24119594
TI  - Prevalence of ocular symptoms in patients with allergic rhinitis: Korean
      multicenter study.
AB  - BACKGROUND: Allergic rhinitis (AR) is often accompanied by multiple ocular
      symptoms. This study aimed to evaluate the prevalence of ocular symptoms and the
      impact of ocular symptoms on the quality of life in patients with AR. METHODS:
      One thousand one hundred seventy-four patients with AR were enrolled from 24
      centers in Korea. They were classified into four groups according to the Allergic
      Rhinitis and Its Impact on Asthma (ARIA) guideline and also classified into
      perennial AR (PAR) and seasonal AR groups. All patients were asked to complete
      the questionnaire regarding the presence of ocular symptoms, such as eye itching,
      watery eyes, and red eyes. The correlation between ocular symptoms and the rest
      of the quality-of-life areas in the Mini-Rhinoconjunctivitis Quality of Life
      Questionnaire (Mini-RQLQ) was also asked. RESULTS: Seven hundred nineteen (61.2%)
      of 1174 patients had ocular symptoms. In detail, the numbers of patients with eye
      itching, watery eyes, red eyes, and other ocular symptoms were 605 (51.5%), 313
      (26.7%), 207 (17.6%), and 66 (5.6%), respectively. Female patients (72.5%)
      complained of ocular symptoms more commonly than male patients (55.1%). The
      patients with moderate-severe persistent AR showed the highest prevalence of
      ocular symptoms. The correlation coefficients between ocular symptoms and the
      rest of the quality-of-life areas in the Mini-RQLQ were statistically significant
      (p < 0.05). CONCLUSION: Sixty-one percent of Korean AR patients experienced
      ocular symptoms. The patients who were women and had PAR and more severe AR
      showed higher prevalence of ocular symptoms. The ocular symptoms might have a
      significant impact on the quality of life in patients with AR.

PMID- 24119595
TI  - Epidemiology of IgE-dependent allergic diseases in elderly patients in Poland.
AB  - BACKGROUND: There is a growing allergy problem in elderly patients. The
      epidemiology of atopic bronchial asthma (BA), allergic rhinitis, and atopic
      dermatitis (AD) was analyzed in an elderly Polish population. METHODS: Subject
      recruitment was conducted at 16 sites representative of Polish rural and urban
      areas, and 7124 subjects, including 4176 women with a mean age of 67.5 +/- 84.9
      years and 2948 men with a mean age of 66.1 +/- 7.2 years, were screened. Medical
      examinations, an original questionnaire, skin-prick testing (SPT) with common
      aeroallergens, and appropriate serum-specific IgE assays were performed. RESULTS:
      Suspicion of atopy was diagnosed in 1900 of the 7124 analyzed patients (26.7%),
      including 1117 women (26.7% of women) and 783 men (26.6% of men). The average
      morbidity associated with age and sex in this population was 5.9% (95% CI, 5.1
      6.4) for BA, 1.6% (95% CI, 15.9-19.3) for AD/eczema, 12.6% (95% CI, 10.8-14.6)
      for seasonal allergic rhinitis, 17.1% (95% CI, 15.9-19.7) for perennial allergic
      rhinitis, and 6.4% (95% CI, 5.1-7.3) for polymorphous atopic disease. The most
      frequent positive results were recorded for the following allergens: mixed grass,
      Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Alternaria.
      CONCLUSION: This study confirms the high prevalence of allergic rhinitis and BA
      in elderly Polish patients. These findings are comparable with those involving
      groups of younger individuals with allergies.

PMID- 24119596
TI  - The use of postoperative topical corticosteroids in chronic rhinosinusitis with
      nasal polyps: a systematic review and meta-analysis.
AB  - BACKGROUND: Topical intranasal corticosteroids (INCSs) are used to control
      disease symptoms in patients with chronic rhinosinusitis with nasal polyposis
      (CRSwNP). The evidence to recommend INCSs as part of the postoperative care is
      limited. This study was designed to assess the efficacy of INCSs in the
      postoperative care of patients undergoing functional endoscopic sinus surgery
      (FESS) during the 1st year postoperatively. METHODS: We searched the Cochrane
      Central Register of Controlled Trials (1995 to May 2012), MEDLINE (January 1948
      to May 2012), EMBASE (January 1980 to May 2012), and the reference lists of
      articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines were followed. Randomized controlled trials (RCT) and cohort
      studies comparing INCSs with placebo or comparing different types of INCSs were
      included. RESULTS: Eleven studies (n = 945 patients) were RCTs and one
      prospective cohort study (n = 32 patients). As measured by the standardized mean
      difference (SMD) INCSs had a beneficial effect on symptom scores (SMD, -1.35; 95%
      CI, -2.05 to -0.64; p = 0.0002; 3 trials; 137 patients) and polyp score (SMD,
      0.53; 95% CI, -0.91 to -0.14; p = 0.007; 5 trials; 223 patients). Compared with
      placebo, the use of INCSs decreased the odds of polyp recurrence (odds ratio,
      0.17; 95% CI, 0.06-0.51; p = 0.002; 2 trials; 74 patients). Two RCTs (n = 105)
      and one cohort study (n = 32) reported normal adrenocorticotropic hormone levels
      postintervention. CONCLUSION: INCS use is a safe therapy in postoperative
      management of CRSwNP patients. INCS showed significant improvement in polyp
      score, patients' symptoms and significant decrease in polyp recurrence in the
      first year postoperatively.

PMID- 24119597
TI  - The effect of maxillary sinus irrigation on early prognostic factors after
      endoscopic sinus surgery: a preliminary study.
AB  - BACKGROUND: Sinus irrigation has been used to treat chronic rhinosinusitis
      refractory to medical and surgical treatments. The aim of this study was to
      evaluate the effect of maxillary sinus saline irrigation on the prevention of
      purulent rhinorrhea, extensive granulation formation, and polyp recurrence after
      endoscopic sinus surgery (ESS). METHODS: This prospective, controlled study was
      approved by the Institutional Review Board of Gachon University Gil Medical
      Center. Between August 1, 2011, and May 31, 2012, we recruited a total of 30
      patients who underwent bilateral ESS. Group A was composed of 15 patients that
      were treated with bilateral maxillary sinus saline irrigation for 2 months after
      ESS. Group B was composed of 15 patients who were followed up during the same
      period after ESS. We checked for persistent purulent discharge, extensive
      granulation, and recurrent polyps in both groups to evaluate the effects of
      maxillary sinus irrigation on their prevention. RESULTS: Age, gender, and
      preoperative Lund-Mackay scores were not significantly different between the two
      groups (p > 0.05). In group A, one patient showed polyp recurrence. In group B,
      one patient showed extensive granulation tissue, two patients showed uncontrolled
      purulent discharge, three patients showed extensive granulation tissues and
      uncontrolled purulent discharge, and one patient showed recurrent polyps (p =
      0.03). In addition, total endoscopic scores in the 3rd month were significantly
      different between groups A and B (p = 0.01). CONCLUSION: Maxillary sinus saline
      irrigation may be effective in the prevention of poor prognostic factors, such as
      persistent purulent discharge, at the early stages after ESS.

PMID- 24119598
TI  - A review of current evidence regarding several key sinonasal disorders.

PMID- 24119599
TI  - Cytological changes in nasal secretions accompanying delayed nasal response to
      allergen challenge.
AB  - BACKGROUND: Patients with allergic rhinitis when challenged with allergen develop
      various types of nasal response, such as an immediate nasal response (INR), late
      nasal response (LNR), dual late nasal response (DLNR), or delayed nasal response
      (DYNR), probably because of different hypersensitivity mechanisms. This study was
      designed to investigate the cytological changes in the nasal secretions (NSs)
      during the DYNR, beginning 24-32 hours, reaching maximum at 32-36 hours, and
      resolving within 56 hours after the nasal provocation tests (NPTs) with
      allergens. METHODS: In 45 allergic rhinitis patients developing 45 positive DYNRs
      (p < 0.01), the NPTs and the phosphate-buffered saline (PBS) controls were
      repeated and supplemented with cytological examination of the NSs and
      determination of interferon (IFN) gamma and IL-4 in nasal lavage fluid (NLF).
      RESULTS: The repeated DYNR (p < 0.001) was accompanied by significant changes (p
      < 0.05) in the counts of neutrophils, monocytes, lymphocytes, epithelial and
      goblet cells, and, to a limited extent, of plasma cells and platelets in the NSs
      and increased concentrations of IFN-gamma but not of IL-4, in NLF between 24 and
      48 hours after the NPT. No significant cytological changes were found in NSs
      during the PBS controls (p > 0.1). CONCLUSION: The DYNR is associated with
      cytological profiles in the NS different from those observed during the INR or
      LNR. The significant count changes of neutrophils, monocytes, lymphocytes,
      epithelial and goblet cells in NSs, and increased IFN-gamma but not of IL-4
      concentrations in the NLF, suggest a possible involvement of the cell-mediated
      hypersensitivity in the DYNR. These results also emphasize the diagnostic value
      of NPTs combined with cytological examination of the NSs in patients with nasal
      allergy.

PMID- 24119600
TI  - Increased expression of YKL-40 in mild and moderate/severe persistent allergic
      rhinitis and its possible contribution to remodeling of nasal mucosa.
AB  - BACKGROUND: Prominent expression of YKL-40 has been associated with pathological
      conditions characterized by tissue remodeling. We determined the expression level
      and distribution pattern of YKL-40 in allergic nasal mucosa and evaluated the
      effect of YKL-40 on the proliferation and migration of fibroblasts, the
      production of the mediators related to tissue remodeling, and collagen
      production. Additionally, the cytokine-driven regulation of YKL-40 expression was
      evaluated in cultured epithelial cells. METHODS: The expression of YKL-40 in
      normal, mild, and moderate/severe allergic nasal mucosa was evaluated using real
      time polymerase chain reaction (PCR), Western blot, and immunohistochemistry.
      Fibroblast migration was observed using a scratch wound method, and proliferation
      was determined by the MTT methods. Expression of proteoglycans, transforming
      growth factor (TGF) beta1, MMP2, MMP9, TIMP1, TIMP2, and collagen concentration
      were analyzed in fibroblasts treated with YKL-40. The expression levels of YKL-40
      in cultured epithelial cells were examined after stimulation with mediators
      including Th2 cytokines, interferon (IFN)gamma, and TNF-alpha with real-time PCR
      and ELISA. RESULTS: The expression of YKL-40 was up-regulated in allergic
      rhinitis and distributed in superficial epithelium, submucosal glands, and
      vascular endothelium, in addition to infiltrating cells. TGF-beta1, TIMP1, MMP9,
      and biglycan were up-regulated in fibroblasts on stimulation with YKL-40,
      accompanying increased proliferation and migration, and collagen production. IL
      13, IFN-gamma, and TNF-alpha induced the increased production of YKL-40 in
      cultured epithelial cells. CONCLUSION: YKL-40 is up-regulated in mild and
      moderate/severe persistent allergic rhinitis, and its expression can be regulated
      differentially by different cytokines, possibly contributing to the remodeling of
      nasal mucosa in allergic rhinitis.

PMID- 24119601
TI  - Differential expression of adhesion molecules by sinonasal fibroblasts among
      control and chronic rhinosinusitis patients.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by inflammatory cell
      migration into sinus tissue with resultant inflammation fueled by a milieu of
      cytokines. Fibroblasts may contribute to inflammation through expression of
      leukocyte adhesion molecules such as vascular cell adhesion molecule (VCAM) and
      intercellular adhesion molecule (ICAM). VCAM attracts eosinophils and mast cells
      contributing to Th2 skewing, and ICAM attracts neutrophils and to a lesser
      degree, eosinophils, and contributes to mixed Th1/Th2 skewing. The purpose of
      this study was to compare sinus fibroblast adhesion molecule expression ex vivo
      among CRS subtypes and in vitro after cytokine stimulation. METHODS: Sinus biopsy
      specimens were taken from control patients (n = 13), CRS without nasal polyposis
      (CRSsNP, n = 6), and CRS with nasal polyposis (CRSwNP, n = 15). ex vivo levels of
      VCAM and ICAM were measured by flow cytometry from single cell suspensions of
      tissue biopsy specimens. Changes in VCAM and ICAM expression to cytokine exposure
      were assessed using in vitro cultured sinonasal fibroblasts treated with tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-4, or interferon (IFN)-gamma.
      RESULTS: ex vivo VCAM expression was lowest in controls, higher in CRSsNP, and
      highest in CRSwNP. in vitro stimulation with TNF-alpha and IL-4, but not IFN
      gamma, increased VCAM among CRSsNP, while expression in CRSwNP remained elevated
      with all treatments except IFN-gamma. ex vivo ICAM expression was elevated in
      both CRS subtypes. in vitro stimulation with TNF-alpha and IFN-gamma, but not IL
      4, increased ICAM expression in all patients with the largest effects among the
      CRSsNP subgroup. CONCLUSION: Sinonasal fibroblast expression of adhesion
      molecules in sinusitis varies by disease state and is selectively influenced by
      exposure to inflammatory cytokines.

PMID- 24119603
TI  - Histopathological evaluation of chronic rhinosinusitis: a critical review.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) consists of a constellation of symptoms,
      including facial pressure/pain, hyposmia, rhinorrhea, and nasal congestion. On
      histopathological evaluation, the disease can be divided into
      pathophysiologically distinct subgroups. This study systematically reviews the
      literature regarding the unique histopathological findings of the various
      subtypes of CRS to determine the potential diagnostic value of performing tissue
      analysis of CRS specimens beyond routine hematoxylin and eosin (H&E) staining.
      METHODS: A PubMed search was untaken to identify articles that evaluated the
      histopathological features of CRS. Six hundred fifty-four relevant articles were
      identified and after application of specific exclusion criteria, 71 articles were
      further reviewed in detail. RESULTS: All articles included analysis of tissue
      samples from in-office biopsies or intraoperative specimens of patients who
      underwent sinus surgery. CRS was often further divided into subgroups and
      compared with each other and with a control group. The subgroups included CRS
      with and without nasal polyps, asthmatic and nonasthmatic patients, and with and
      without eosinophilia. Distinct inflammatory mediators were found for the
      different subgroups. Twenty-eight articles evaluated these inflammatory markers
      for their potential value as prognostic indicators. CONCLUSION: CRS is a
      heterogeneous disease based on its histopathological findings. Information that
      is obtainable from light microscopy, but typically goes unreported, can serve as
      valuable prognostic indictors. However, routine H&E staining is suboptimal in
      distinguishing among the various subgroups of CRS. Assessment of specific
      inflammatory mediators in sinus mucosa specimens may help provide prognostic
      information and guide more tailored treatment for the individual patient.

PMID- 24119604
TI  - Estimation of sensitivity and specificity of brain magnetic resonance imaging and
      single photon emission computed tomography in the diagnosis of olfactory
      dysfunction after head traumas.
AB  - BACKGROUND: Olfactory dysfunction has an incidence of 5-10% after head injury.
      Several objective and subjective tests had been proposed. Recent studies showed
      that brain single photon emission computed tomography (SPECT) and brain magnetic
      resonance imaging (MRI) have good diagnostic value in this era in which the most
      common sites of involvement were olfactory bulb and olfactory nerve in MRI and
      frontal lobe in SPECT. This study aimed to estimate the sensitivity and
      specificity of brain MRI and brain SPECT in the diagnosis of traumatic hyposmia
      and anosmia. METHODS: From February 2009 to March 2011, 63 patients with head
      injury and smell complaint were selected for this study. Using an identification
      test and a threshold smell test, 28 were anosmic and 27 had hyposmia and the
      remaining 8 were normosmic. All of them underwent brain MRI and SPECT. RESULTS:
      The sensitivity of SPECT was 81.5 and 85.7% in hyposmia and anosmia,
      respectively. Its specificity was 87.5% in anosmia and 87.7% in anosmia. MRI
      sensitivity was 66.7% in hyposmia but 82.1% in anosmia. Its specificity was 85.7%
      in anosmia and 87.7% in anosmia. If MRI and SPECT were considered together, the
      sensitivity was 92.3% in hyposmia and 92% in anosmia, but the specificity was 87%
      in both cases. CONCLUSION: According to our study, both brain MRI and SPECT have
      high sensitivity and specificity in the diagnosis of traumatic anosmia, although
      brain SPECT is slightly superior to MRI. If the two techniques are applied
      together, the accuracy will be increased.

PMID- 24119602
TI  - Cystic fibrosis chronic rhinosinusitis: a comprehensive review.
AB  - BACKGROUND: Advances in the care of patients with cystic fibrosis (CF) have
      improved pulmonary outcomes and survival. In addition, rapid developments
      regarding the underlying genetic and molecular basis of the disease have led to
      numerous novel targets for treatment. However, clinical and basic scientific
      research focusing on therapeutic strategies for CF-associated chronic
      rhinosinusitis (CRS) lags behind the evidence-based approaches currently used for
      pulmonary disease. METHODS: This review evaluates the available literature and
      provides an update concerning the pathophysiology, current treatment approaches,
      and future pharmaceutical tactics in the management of CRS in patients with CF.
      RESULTS: Optimal medical and surgical strategies for CF CRS are lacking because
      of a dearth of well-performed clinical trials. Medical and surgical interventions
      are supported primarily by level 2 or 3 evidence and are aimed at improving
      clearance of mucus, infection, and inflammation. A number of novel therapeutics
      that target the basic defect in the cystic fibrosis transmembrane conductance
      regulator channel are currently under investigation. Ivacaftor, a corrector of
      the G551D mutation, was recently approved by the Food and Drug Administration.
      However, sinonasal outcomes using this and other novel drugs are pending.
      CONCLUSION: CRS is a lifelong disease in CF patients that can lead to substantial
      morbidity and decreased quality of life. A multidisciplinary approach will be
      necessary to develop consistent and evidence-based treatment paradigms.

PMID- 24119605
TI  - Systemic effects and safety of triamcinolone-impregnated nasal packing after
      endoscopic sinus surgery: a randomized, double-blinded, placebo-controlled study.
AB  - BACKGROUND: Steroid-infused absorbable nasal dressings after endoscopic sinus
      surgery (ESS) have been used to improve wound healing and to reduce the
      recurrence of polyps. However, their systemic effects are not well known. The
      purpose of this study was to evaluate the systemic effects and safety of steroid
      impregnated absorbable nasal packing after ESS. METHODS: Patients who underwent
      bilateral ESS for chronic rhinosinusitis were recruited and randomized into two
      groups. Ten patients in the triamcinolone (TA) group received a TA (20 mg)-soaked
      bioabsorbable dressing in both nasal cavities while 10 patients in the control
      group took saline-impregnated dressing in both nasal cavities. Nasal dressings
      were not removed until postoperative day 10. Serum cortisol, 12-hour urine
      cortisol, serum adrenal-corticotropic hormone (ACTH), and serum osteocalcin were
      measured preoperatively and on postoperative days 2 and 10. Serum cortisol levels
      were checked 1 day after surgery additionally, while urine cortisol levels were
      not checked at postoperative day 10. RESULTS: All 20 patients completed this
      study. The serum cortisol levels were significantly suppressed at postoperative
      days 1 and 2 in the TA group. Serum ACTH and 12-hour urine cortisol levels were
      lower 2 days after surgery in the TA group, although these changes were not
      statistically significant. There were no differences in all other parameters
      between the TA and control groups on postoperative day 10. CONCLUSIONS: TA
      impregnated nasal dressings suppress serum cortisol levels during the early
      postoperative period. This systemic effect was recovered gradually and normalized
      10 days after the operation.

PMID- 24119606
TI  - Inferior turbinate hypertrophy: review and graduated approach to surgical
      management.
AB  - BACKGROUND: Surgical techniques for managing inferior turbinate hypertrophy (ITH)
      vary widely and have evolved substantially in the past four decades as new
      technologies have emerged. METHODS: Literature review. RESULTS: Inferior
      turbinate (IT) procedures can be categorized as: simple turbinate outfracture;
      turbinoplasty techniques such as extramucosal destruction, and submucosal tissue
      removal; and extramural turbinate resection (partial or complete). Each of these
      approaches has advantages and drawbacks. Considerations for technique selection
      include clinical setting (in-office versus operating room), cost of the devices
      used, efficacy of the procedure to relieve nasal obstruction, and minimizing
      postoperative complications such as nuisance bleeding, adhesion formation, and
      crusting. CONCLUSION: There are a variety of contemporary surgical techniques
      used for IT reduction. This article highlights the available literature and gaps
      in current knowledge. A graduated approach to the management of ITH will be
      presented.

PMID- 24119607
TI  - Comparison of ropivacaine, bupivacaine, prilocaine, and lidocaine in the
      management of pain and hemorrhage during nasal pack removal.
AB  - BACKGROUND: This study investigates the effects of local anesthetics application
      on pain and hemorrhage caused by nasal pack removal. METHODS: The study included
      140 patients. Of these, 72 were women and 68 were men. The mean age and weight of
      the patients were 33.67 +/- 10.2 years (range, 21-63 years) and 69.6 +/- 13.6 kg.
      The patients were divided randomly into four groups. Three of the four groups
      received one of the local anesthetics studied in our trial (lidocaine +
      adrenaline, 0.25% bupivacaine, or 2% prilocaine) before removal of the nasal
      packing material and the control group received saline solution. Local
      anesthetics and 0.9% saline solution were applied to Merocel nasal packs 15
      minutes before removal. Each patient was given a questionnaire where verbal
      analog score and amount of postoperative hemorrhage was noted. RESULTS: The mean
      pain score was 3.5 +/- 1.2 (median, 4; range, 3-5) in the lidocaine group, 4.5 +/
      1.2 (median, 4; range 3-5) in the prilocaine group, 4.7 +/- 1.3 (median, 6;
      range, 3-5) in the bupivacaine group, and 6.35 +/- 1.2 (median, 6; range, 5-7) in
      the saline group during nasal packing removal. The lidocaine group had
      significantly better pain scores versus other groups (p < 0.05). Bupivacaine and
      prilocaine had significantly better pain scores versus the control group,
      respectively. Analysis of bleeding scores after pack removal showed that all
      three study groups had significantly better bleeding scores versus the control
      saline group (p < 0.05). The lidocaine group had significantly less bleeding
      score than bupivacaine and prilocaine groups (p < 0.05). CONCLUSION: Topical
      lidocaine application before removal of nasal packs in patients who undergo nasal
      septal surgery can decrease discomfort and bleeding and improve patient
      tolerance.

PMID- 24119608
TI  - Expanded endonasal approach using vascularized septal flap reconstruction for
      skull base tumors has a negative impact on sinonasal symptoms and quality of
      life.
AB  - BACKGROUND: Endoscopic transsphenoidal surgery is currently the optimal treatment
      for skull base tumors. This study was designed to assess patient's sinonasal
      symptoms and quality of life (QoL) after resection of pituitary adenoma or skull
      base tumors using vascularized septal flap (VSF) reconstruction. METHODS:
      Patients with pituitary adenoma underwent the transnasal transsphenoidal
      endoscopic approach (TTEA; n = 38), and patients with other benign parasellar
      tumors underwent the expanded endonasal approach (EEA; n = 17) with VSF.
      Assessment of sinonasal symptoms and QoL by the 36-item Short-Form (SF-36) and
      the 31-item Rhinosinusitis Outcome Measure (RSOM-31) were performed before and 3
      months after surgery. RESULTS: At baseline, the total seven-sinonasal symptom
      score (T7SSS) was similar between both groups. After surgery, T7SSS significantly
      increased in EEA but not in TTEA patients. EEA patients reported more smell loss
      (40.1 +/- 26.2; p < 0.05) and posterior nasal discharge (49.3 +/- 30.1; p < 0.05)
      than TTEA patients (21.6 +/- 30.9 and 22.5 +/- 27.5, respectively). At baseline,
      both groups had poorer SF-36 compared with the general population. TTEA patients
      had poorer QoL (on general health, vitality, and mental health) than EEA
      patients. After surgery, TTEA patients showed impaired physical role and bodily
      pain compared with baseline, and EEA patients showed impaired physical role and
      mental health. At baseline, RSOM scores were similar in TTEA and EEA groups.
      After surgery, EEA but not TTEA patients reported poorer nasal and general
      symptoms. CONCLUSION: The EEA with VSF produces more sinonasal symptoms than
      pituitary surgery, surgery for skull base and pituitary tumors has negative
      impact on QoL, and functioning tumors have no further negative effect on
      sinonasal symptoms and QoL.

PMID- 24119609
TI  - Prognosis for sixth nerve palsy arising from paranasal sinus disease.
AB  - BACKGROUND: The abducens nerve, cranial nerve VI (CNVI), is the medial-most nerve
      in the cavernous sinus. Its close proximity to the sphenoid sinus makes it
      susceptible to injury, invasion, or compression from a sphenoid pathology leading
      to horizontal gaze diplopia. A wide range of literature describes myriad causes
      for CNVI palsy, but there is a lack of references that point to paranasal sinus
      pathology as an etiology, as well as the prognosis and timeline for resolution.
      Here, we describe a series of patients that presented with CNVI palsy, their
      management, and prognosis for recovery. This study was designed to evaluate and
      understand prognostic factors predicting disease course and likelihood of
      resolution in patients with abducens nerve palsy. METHODS: A multi-institutional
      retrospective review was performed of all patients presenting with CNVI palsy
      between 2009 and 2012. The demographic data, radiological features, treatment
      regimens, and disease courses were analyzed. RESULTS: Fifteen patients at four
      institutions were identified. Seven patients had neoplasms originating from the
      paranasal sinuses, three suffered from allergic fungal sinusitis, three patients
      had invasive fungal sinusitis, one patient had fibrous skull base dysplasia, and
      one had chronic bacterial sinusitis. The average follow-up time from presentation
      was 9 months (range, 1-16 months). Thirteen patients underwent surgery, three
      received chemotherapy, and four had radiation therapy. CNVI palsy resolved in 50%
      of the cases, with an average time to resolution of 6 weeks (range, 2-12 weeks).
      CONCLUSION: Paranasal sinus pathology is a rare cause of CNVI palsy. A number of
      factors may help to predict prognosis in these patients. Masses compressing, but
      not destroying or invading, the cavernous sinus had optimal posttreatment
      outcomes with full resolution occurring as early as 2 weeks. Destructive lesions
      that invaded CNVI and its vasculature, i.e., invasive fungus, were negative
      indicators for recovery. Knowledge of factors that affect recovery can help
      clinicians predict disease course and prognosis for resolution of the defect.

PMID- 24119611
TI  - A simplified ultrasound-based edema score to assess lung injury and clinical
      severity in septic patients.
AB  - BACKGROUND: Lung ultrasound (US) is an excellent tool to assess lung edema in a
      myriad of different clinical situations. We hypothesized that lung US might also
      be a good prognostic and management instrument in septic patients, regardless of
      disease severity. METHODS: This was a prospective observational cohort study at
      an urban academic emergency department (ED). Inclusion criteria were as follows:
      septic patients, at least 18 years old, admitted at the ED of a tertiary
      hospital. A simplified lung edema scoring system (SLESS) was developed, and 6
      thoracic regions were evaluated. Four different lung US patterns were considered,
      from normal aeration to total consolidation. To evaluate disease severity, the
      SLESS was compared with the Mortality in Emergency Department Sepsis Score and
      the third version of the Simplified Acute Physiology Score scoring systems.
      Aiming to assess the effect of the lung edema in the gas exchange, the SLESS was
      compared with the Pao2/fraction of inspired oxygen ratio. RESULTS: Sixty-one
      patients were enrolled in a 3-month period. The SLESS had a good correlation with
      the Mortality in Emergency Department Sepsis Score and Simplified Acute
      Physiology Score (r = 0.53 and r = 0.55, respectively; P < .001 for both) and a
      negative correlation with the Pao2/fraction of inspired oxygen ratio (r = -0.62;
      P < .001). The SLESS also showed correlation with the respiratory rate (r = 0.45;
      P = .0003). The odds ratio for death related to the SLESS was 1.370 (95%
      confidence interval, 1.109-1.691; P = .0035). CONCLUSION: The SLESS is an easy
      and practical scoring system. It might be a useful tool to predict severity of
      disease in sepsis patients. The SLESS might also be able to be correlated with
      the oxygen exchange.

PMID- 24119612
TI  - Extensive retroperitoneal air, pneumomediastinum, and subcutaneous air secondary
      to stercoral perforation.
AB  - Stercoral perforation is an uncommon cause of large intestinal perforation that
      is typically the result of chronic constipation. Historically, this disease
      process has a devastatingly high mortality rate, and recent evidence questions
      the incidence of the disease, once thought to be scarce. We report the case of an
      elderly woman presenting with symptoms related to mediastinal and soft tissue air
      in the neck from dissection of air retroperitoneally from stercoral perforation.
      She had minimal abdominal complaints and no history of chronic constipation. The
      emergency provider should be aware that this disease entity exists and should be
      cognizant that retroperitoneal pathology may present with complaints referable to
      the chest or even neck with a paucity of abdominal findings.

PMID- 24119613
TI  - Validation of 4% albumin as a diluent in the Bethesda Assay for FVIII inhibitors.
AB  - INTRODUCTION: External quality assurance programs show the Nijmegen Bethesda
      Assay for FVIII inhibitors improves test specificity compared to the Classic
      Bethesda Assay but its uptake has been slow possibly due to the cost of using
      FVIII deficient plasma as diluent. This study was conducted to determine if
      modifying the Nijmegen Bethesda assay by replacement of FVIII deficient plasma
      with 4% as a diluent would be suitable for for measuring FVIII inhibitors.
      MATERIALS AND METHODS: The titres of 59 samples from 35 patients with FVIII
      inhibitors were determined in parallel tests by the Nijmegen Bethesda Assay and
      and the modified Nijmegen assay. Method reproducibility was assessed on inhibitor
      containing samples from seven individuals covering a range of titres from 1-200
      Bethesda units/mL. RESULTS: The all-sample geometric mean titre was 6.73 Bethesda
      units/mL for the Nijmegen Bethesda Assay and 7.54 Bethesda units/mL for the
      modified Nijmegen assay. No sample was found where a difference in measured titre
      between methods would have altered clinical management. Agreement was very close
      in samples with titres less than 2BU/mL. Both assays gave inhibitor titres in
      external quality assurance samples of close to consensus values. The average
      between-run coefficients of variation were 8.6% for the Nijmegen Bethesda Assay
      and 7.9% for the modified Nijmegen assay. CONCLUSIONS: The modified Nijmegen
      assay using 4% albumin as the sample diluent showed good overall comparability to
      our existing Nijmegen Bethesda Assay and is substantially more cost-effective,
      making it a reasonable alternative for measuring FVIII inhibitors.

PMID- 24119614
TI  - Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic
      mammalian chitinase loss as a corpus atrophy marker.
AB  - BACKGROUND: The majority of gastric cancer cases are believed to be caused by
      chronic infection with the bacterium Helicobacter pylori, and atrophic corpus
      gastritis is a predisposing condition to gastric cancer development. We aimed to
      increase understanding of the molecular details of atrophy by performing a global
      transcriptome analysis of stomach tissue. METHODS: Biopsies from patients with
      different stages of H. pylori infection were taken from both the antrum and
      corpus mucosa and analyzed on microarrays. The stages included patients without
      current H. pylori infection, H. pylori-infected without corpus atrophy and
      patients with current or past H. pylori-infection with corpus-predominant
      atrophic gastritis. RESULTS: Using clustering and integrated analysis, we found
      firm evidence for antralization of the corpus mucosa of atrophy patients. This
      antralization harbored gain of gastrin expression, as well as loss of expression
      of corpus-related genes, such as genes associated with acid production, energy
      metabolism and blood clotting. The analyses provided detailed molecular evidence
      for simultaneous intestinal metaplasia (IM) and spasmolytic polypeptide
      expressing metaplasia (SPEM) in atrophic corpus tissue. Finally, acidic mammalian
      chitinase, a chitin-degrading enzyme produced by chief cells, was shown to be
      strongly down-regulated in corpus atrophy. CONCLUSIONS: Transcriptome analysis
      revealed several gene groups which are related to development of corpus atrophy,
      some of which were increased also in H. pylori-infected non-atrophic patients.
      Furthermore, loss of acidic chitinase expression is a promising marker for corpus
      atrophy.

PMID- 24119615
TI  - Effectiveness and neural mechanisms associated with tDCS delivered to premotor
      cortex in stroke rehabilitation: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: More than 60% of stroke survivors experience residual deficits of the
      paretic upper limb/hand. Standard rehabilitation generates modest gains.
      Stimulation delivered to the surviving Primary Motor Cortex in the stroke
      affected hemisphere has been considered a promising adjunct. However, recent
      trials challenge its advantage. We discuss our pilot clinical trial that aims to
      address factors implicated in divergent success of the approach. We assess
      safety, feasibility and efficacy of targeting an alternate locus during
      rehabilitation- the premotor cortex. In anticipating variance across patients, we
      measure neural markers differentiating response from non-response.
      METHODS/DESIGN: In a randomized, sham-controlled, double-blinded pilot clinical
      study, patients with chronic stroke (n = 20) are assigned to receive transcranial
      direct current stimulation delivered to the premotor cortex or sham during
      rehabilitation of the paretic arm/hand. Patients receive the designated
      intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess
      hand function and patients' reports of use of paretic hand. A general linear
      mixed methods model will analyze changes from pre- to post-intervention.
      Responders and non-responders will be compared upon baseline level of function,
      and neural substrates, including function and integrity of output tracts, bi
      hemispheric balance, and lesion profile. Incidence of adverse events will be
      compared using Fisher's Exact test, while rigor of blinding will be assessed with
      Chi-square analysis to ascertain feasibility. DISCUSSION: Variable success of
      cortical stimulation in rehabilitation can be related to gaps in theoretical
      basis and clinical investigation. Given that most patients with severe deficits
      have damage to the primary motor cortex or its output pathways, it would be
      futile to target stimulation to this site. We suggest targeting premotor cortex
      because it contributes substantially to descending output, a role that is
      amplified with greater damage to the motor cortex. With regards to clinical
      investigation, paired cortical stimulation in rehabilitation has been compared to
      rehabilitation alone in unblinded trials or to unconvincing sham conditions.
      Transcranial direct current stimulation, a noninvasive technique of brain
      stimulation, which offers a more effective placebo and has a favorable safety
      feasibility profile, may improve scientific rigor. Neural markers of response
      would help inform patient selection for future clinical trials so we can address
      limitations of recent negative studies. TRIAL REGISTRATION: NCT01539096.

PMID- 24119616
TI  - Interferon regulatory factor-1 together with reactive oxygen species promotes the
      acceleration of cell cycle progression by up-regulating the cyclin E and CDK2
      genes during high glucose-induced proliferation of vascular smooth muscle cells.
AB  - BACKGROUND: The high glucose-induced proliferation of vascular smooth muscle
      cells (VSMCs) plays an important role in the development of diabetic vascular
      diseases. In a previous study, we confirmed that Interferon regulatory factor-1
      (Irf-1) is a positive regulator of the high glucose-induced proliferation of
      VSMCs. However, the mechanisms remain to be determined. METHODS: The levels of
      cyclin/CDK expression in two cell models involving Irf-1 knockdown and
      overexpression were quantified to explore the relationship between Irf-1 and its
      downstream effectors under normal or high glucose conditions. Subsequently, cells
      were treated with high glucose/NAC, normal glucose/H2O2, high glucose/U0126 or
      normal glucose/H2O2/U0126 during an incubation period. Then proliferation,
      cyclin/CDK expression and cell cycle distribution assays were performed to
      determine whether ROS/Erk1/2 signaling pathway was involved in the Irf-1-induced
      regulation of VSMC growth under high glucose conditions. RESULTS: We found that
      Irf-1 overexpression led to down-regulation of cyclin D1/CDK4 and inhibited cell
      cycle progression in VSMCs under normal glucose conditions. In high glucose
      conditions, Irf-1 overexpression led to an up-regulation of cyclin E/CDK2 and an
      acceleration of cell cycle progression, whereas silencing of Irf-1 suppressed the
      expression of both proteins and inhibited the cell cycle during the high glucose
      induced proliferation of VSMCs. Treatment of VSMCs with antioxidants prevented
      the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of
      cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose
      conditions. In contrast, under normal glucose conditions, H2O2 stimulation and
      Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2
      expression and promoted cell cycle acceleration. In addition, overexpression of
      Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were
      treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of
      VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle
      progression under high glucose or normal glucose/H2O2 conditions. CONCLUSIONS:
      These results demonstrate that the downstream effectors of Irf-1 are cyclin
      E/CDK2 during the high glucose-induced proliferation of VSMCs, whereas they are
      cyclin D1/CDK4 in normal glucose conditions. The Irf-1 overexpression-induced
      proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration
      of cell cycle progression are associated with ROS/Erk1/2 signaling pathway under
      high glucose conditions.

PMID- 24119617
TI  - Brain natriuretic peptide in acute ischemic stroke.
AB  - Elevated serum brain natriuretic peptide (BNP) levels are associated with
      cardioembolic stroke mainly because of atrial fibrillation (AF). However, the
      mechanisms of increased serum BNP levels are hitherto unclear. We aimed to
      identify the factors associated with increased BNP levels in patients with acute
      ischemic stroke. We measured serum BNP levels in consecutive patients aged 18
      years or older. Stroke subtypes were classified using the Trial of ORG 10172 in
      Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking
      status, alcohol consumption status, hypertension, diabetes mellitus,
      dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and
      anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr),
      beta-thromboglobulin, platelet factor 4, thrombin-antithrombin complex, and d
      dimer levels. We further determined the relationship between serum BNP and intima
      media thickness, left ventricular ejection fraction, size of infarction, National
      Institutes of Health Stroke Scale score on admission, and modified Rankin Scale
      (mRS) score at discharge. Of the 231 patients (mean age, 71 +/- 12 years) with
      acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly
      correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P =
      .004). BNP levels were significantly higher in patients with larger infarcts,
      higher mRS scores, and higher CHADS2 scores. The levels were higher in patients
      with larger infarcts, higher mRS scores at discharge, and higher CHADS2 scores
      among AF patients. 

PMID- 24119618
TI  - Synthetic cannabis and acute ischemic stroke.
AB  - An association between marijuana use and stroke has been previously reported.
      However, the health risks of newer synthetic cannabinoid compounds are less well
      known. We describe 2 cases that introduce a previously unreported association
      between synthetic cannabis use and ischemic stroke in young adults. A 22-year-old
      woman presented with dysarthria, left hemiplegia, and left hemianesthesia within
      hours of first use of synthetic cannabis. She was healthy and without identified
      stroke risk factors other than oral contraceptive use and a patent foramen ovale
      without venous thromboses. A 26-year-old woman presented with nonfluent aphasia,
      left facial droop, and left hemianesthesia approximately 12 hours after first use
      of synthetic cannabis. Her other stroke risk factors included migraine with aura,
      oral contraceptive use, smoking, and a family history of superficial
      thrombophlebitis. Both women were found to have acute, large-territory
      infarctions of the right middle cerebral artery. Our 2 cases had risk factors for
      ischemic stroke but were otherwise young and healthy and the onset of their
      deficits occurred within hours after first-time exposure to synthetic cannabis.
      Synthetic cannabis use is an important consideration in the investigation of
      stroke in young adults. 

PMID- 24119619
TI  - Nontraumatic convexity subarachnoid hemorrhage: different etiologies and
      outcomes.
AB  - BACKGROUND: Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a rarely
      reported condition with multiple etiologies. We report the clinical presentation,
      imaging findings, etiologies, and long-term outcomes of a case series of cSAH.
      METHODS: We retrospectively analyzed consecutive cases of cSAH, admitted at a
      Stroke Unit of a tertiary hospital (January 2006 to March 2012). Recorded
      variables were demographics, clinical presentation, complementary investigation,
      etiology, and outcome. RESULTS: We included 15 patients (9 men, median age of 65
      years), 7% of the 210 nontraumatic SAH patients in this period. The most common
      clinical manifestation was a focal neurologic deficit. Predominant location of
      the cSAH was frontal. In 5 cases, there was a clinical significant internal
      carotid artery (ICA) atheromatous stenosis, ipsilateral to cSAH. Two patients had
      a possible cerebral amyloid angiopathy (CAA) at presentation. There were 2 cases
      of reversible cerebral vasoconstriction syndrome, 1 cerebral venous thrombosis, 2
      dural fistulae, and 3 undetermined. Short-term outcomes were good in most
      patients. At follow-up (24.3 months), 2 of the patients with undetermined
      etiology had a lobar hematoma conferring a severe disability, and the diagnosis
      of CAA was made. There were no other relevant events or added disability in the
      other patients. CONCLUSIONS: Significant ICA atherosclerotic stenosis was the
      most frequent cause of cSAH in our series, reinforcing that cSAH should prompt
      vascular imagiological evaluation including cervical vessels. Outcomes in cSAH
      seem to be related to etiology. Patients with undetermined etiology should be
      followed up because cSAH may be the first manifestation of CAA.

PMID- 24119620
TI  - Socioeconomic disparities in the utilization of mechanical thrombectomy for acute
      ischemic stroke.
AB  - BACKGROUND: Previous studies have demonstrated that socioeconomic disparities in
      access to treatment of cerebrovascular diseases exist. We studied the Nationwide
      Inpatient Sample (NIS) to determine if disparities exist in utilization of
      mechanical thrombectomy for acute ischemic stroke. METHODS: Using the NIS for the
      years 2006-2010, we selected all discharges with a primary diagnosis of acute
      ischemic stroke. Patients who received mechanical thrombectomy for stroke were
      identified by using the International Classification of Diseases, Ninth Revision,
      procedure code 39.74. We examined the utilization rates of mechanical
      thrombectomy by race/ethnicity (white, black, Hispanic, and Asian/Pacific
      Islander), income quartile (first, second to third, and fourth), and insurance
      status (Medicare, Medicaid, self-pay, and private). We also studied thrombectomy
      utilization rates at hospitals that performed thrombectomy. RESULTS: From 2006 to
      2010, 2,087,017 patients were hospitalized with a primary diagnosis of acute
      ischemic stroke; 8946 patients (.4%) received mechanical thrombectomy. Compared
      with white patients, black patients had significantly lower rates of overall
      mechanical thrombectomy utilization (odds ratio [OR] = .59, 95% confidence
      interval [CI] = .55-.64, P < .0001) and at centers that offered mechanical
      thrombectomy (OR = .44, 95% CI = .41-.47, P < .0001). Compared with patients in
      the highest income quartile, patients in the lowest income quartile had
      significantly lower rates of mechanical thrombectomy utilization both overall (OR
      = .66, 95% CI = .62-.70, P < .0001) and at centers that offered mechanical
      thrombectomy (OR = .80, 95% CI = .75-.84, P < .0001). Compared with patients with
      private insurance, self-pay patients had significantly lower mechanical
      thrombectomy utilization both overall (OR = .71, 95% CI = .64-.78, P < .0001) and
      at centers that offered mechanical thrombectomy (OR = .81, 95% CI = .74-.90, P <
      .0001). CONCLUSIONS: Significant socioeconomic disparities exist in the
      utilization of mechanical thrombectomy in the United States.

PMID- 24119621
TI  - Stroke in Switzerland: social determinants of treatment access and cost of
      illness.
AB  - BACKGROUND: Few useful empirical data on stroke are available for Switzerland.
      The aim of this study was to collect data on the use of medical resources and
      associated costs among stroke patients. Special attention was paid to possible
      correlations between epidemiologic indicators, sociodemographic variables,
      resource use, and costs. METHODS: We carried out a representative population
      survey of 19,123 households in the German- and French-speaking parts of
      Switzerland with computer-assisted telephone interviews in 2005. Detailed
      sociodemographic data and information on the use of resources were collected from
      509 individuals aged 15-75 years who had cared for a stroke patient in the past 1
      2 years. RESULTS: In the last 1-2 years, a total of 7.8% of households were
      affected by stroke in the German-speaking part of Switzerland, whereas only 4.3%
      of households were affected in the French-speaking part of Switzerland (odds
      ratio [OR] = 1.89, P < .001). Based on the length of stay, the total cost of
      inpatient treatment and rehabilitation during the average 1-year observation
      period was estimated at ?40,090. Stroke therefore caused approximately 2.9% of
      all inpatient costs in Switzerland. Patients with supplementary insurance were
      treated more frequently as inpatients than patients with statutory insurance (OR:
      2.14, P = .014), and patients with a low household income were referred less
      frequently to an inpatient rehabilitation facility than those with medium or high
      household income (OR = .58, P < .05). CONCLUSIONS: This survey confirms the
      medical and economic importance of stroke and supplements the existing European
      data. Further research is needed in regard to incidence differences in stroke
      across Switzerland. Patients without supplementary insurance or with low
      household income were less likely to receive inpatient treatment.

PMID- 24119622
TI  - Peripheral monocyte count is associated with case fatality after intracerebral
      hemorrhage.
AB  - BACKGROUND: Leukocytosis is associated with hemorrhage volume and early
      neurologic deterioration after intracerebral hemorrhage (ICH). We examined total
      white blood cell (WBC) count, absolute monocyte count (AMC), and absolute
      neutrophil count (ANC) as potential readily available prognostic biomarkers in
      human ICH. METHODS: In a retrospective study, adult patients aged 18 years or
      older who presented to 1 of 2 local hospitals with nontraumatic ICH from July
      2008 to December 2009 within 12 hours of symptom onset were identified.
      Demographics, Glasgow Coma Scale (GCS), ICH volume, ICH location, and 30-day case
      fatality rates were determined. Total WBC count, ANC, AMC, and hemoglobin
      concentration were determined. Linear and logistic regressions were used to
      evaluate factors associated with baseline ICH volume (log transformed) and 30-day
      case fatality, respectively. RESULTS: Of the 186 patients, mean (+/-SD) age was
      67.3 +/- 14.8 years; 51% were men and 22% were black. Median (interquartile
      range) ICH volume was 12.8 (4.9, 29.4) mL. After adjusting for patient age and
      initial hemoglobin, higher initial WBC count (P = .0009) and higher ANC (P =
      .006) were associated with higher ICH volume, whereas AMC was not (P = .4). After
      adjusting for patient age, GCS, intraventricular hemorrhage (+/-), stroke
      location, and ICH volume, baseline AMC was associated with greater odds of 30-day
      case fatality (odds ratio 2.26, 95% confidence interval 1.10-4.65, P = .03).
      CONCLUSIONS: The association of AMC with higher 30-day case fatality after ICH is
      hypothesis generating. Given the lack of association between presenting AMC and
      ICH volume, AMC may contribute to secondary injury after ICH (hematoma expansion
      and/or cerebral edema).

PMID- 24119623
TI  - Incidence and cost of stroke and hemorrhage in patients diagnosed with atrial
      fibrillation in France.
AB  - BACKGROUND: Stroke represents a major complication of atrial fibrillation (AF).
      The current anticoagulation options for stroke prevention increase hemorrhage
      risk. The objective of the study was to estimate the incidence and costs of
      hospitalization for stroke and hemorrhage in patients with AF who are eligible
      for stroke prevention. METHODS: Patients hospitalized for AF were identified from
      the French National hospital database (Programme Medicalise des Systemes
      d'Information) and a calculated stroke risk score (congestive heart failure,
      hypertension [blood pressure consistently >140/90 mm Hg], age >=75 years,
      diabetes mellitus, and previous stroke, transient ischemic attack [CHADS2]).
      Adult patients eligible for stroke prevention (CHADS2 >0) were enrolled. The
      incidence of hospitalization for stroke and hemorrhage was calculated over a 2
      year period. Costs of acute care were determined using diagnosis related groups
      (DRGs) and corresponding National Hospital Tariffs. Rehabilitation costs were
      analyzed for patients with strokes and classified by stroke severity. RESULTS:
      Sixty-one thousand five hundred eighty-two patients were identified with a mean
      age of 75.0 +/- 11.0 years and a mean CHADS2 score of 1.90 +/- 0.99. The 24-month
      cumulative incidence of any stroke was 32.1 cases/1,000 patients with AF
      (ischemic, 60%; hemorrhagic, 24%; unspecified, 16%), and that of hemorrhage was
      53.1 cases/1,000 patients with AF (gastrointestinal, 26%; intracranial, 5%;
      other, 69%). The mean costs of ischemic and hemorrhagic strokes were ?4,848 and
      ?7,183 (mild), ?10,909 and ?14,298 (moderate), ?29,065 and ?29,701 (severe), and
      ?6,035 and ?4,590 (fatal), respectively. The mean costs of hemorrhage by type
      were ?3,601 (gastrointestinal), ?7,331 (intracranial), ?3,941 (other major), and
      ?2,552 (nonmajor). CONCLUSIONS: The incidence and cost of hospitalization for
      hemorrhage should be considered in the global burden of AF. These data should be
      useful for pharmacoeconomic evaluation of new oral anticoagulant medications.
      Such real-world studies may be relevant for monitoring mid- to long-term
      morbidity and mortality in the AF population.

PMID- 24119624
TI  - Imaging and clinical predictors of unfavorable outcome in medically treated
      symptomatic intracranial atherosclerotic disease.
AB  - BACKGROUND: Patients with symptomatic intracranial atherosclerotic disease
      (sICAD) have an increased risk of stroke and vascular death. The aim of the study
      was to evaluate the natural history and outcome of patients with sICAD treated
      medically. METHODS: The study population was first-ever transient ischemic attack
      (TIA) or stroke patients presenting to our institute who on vascular imaging had
      isolated intracranial atherosclerosis as cause of their symptoms and have a
      follow-up of 90 days. Unfavorable outcome was defined as occurrence of TIA,
      stroke, acute coronary event, and/or vascular death. RESULTS: Fifty-three (11.8%)
      of the 449 ischemic stroke patients had sICAD. The risk of stroke in sICAD was
      8.9%, 11.1%, 13.3%, and 15.6% in first 7 days, 30 days, 90 days, and 1 year,
      respectively. Five (11.1%) had cardiovascular events and accounted for 50% of
      mortality. The predictors of unfavorable outcome were presented as limb weakness
      (85.7% versus 58.8%, hazard ratio 1.5; 95% confidence interval [CI], .05-.9; P =
      .04), National Institutes of Health Stroke Scale (NIHSS) score 8 at admission
      (50% versus 5.9%, hazard ratio 8.5; 95% CI, .007-.5; P = .02), magnetic resonance
      imaging (MRI) with multiple diffusion-weighted imaging (DWI) lesions (65.4%
      versus 26.7%; 95% CI, .04-.7; P = .01), and angiography suggestive of diffuse
      atherosclerosis (50% versus 11.8%; 95% CI, odds ratio .02-.7; P = .009). On
      stepwise multiple regression, variables for unfavorable outcome were NIHSS score
      of 8 or more at admission (P = .001), multiple DWI lesion on MRI (P = .04), and
      diffuse atherosclerosis on angiography (P = .006). CONCLUSION: The patients with
      sICAD have a high risk of stroke and cardiac events even on aggressive medical
      treatment. Clinical and imaging features can identify this high-risk group.

PMID- 24119625
TI  - Neurologic improvement without angiographic improvement after antithyroid therapy
      in a patient with Moyamoya syndrome.
AB  - Moyamoya disease with special complications, including Graves' disease, is called
      as moyamoya syndrome. A 22-year-old Japanese woman had left middle cerebral
      artery (MCA) territory infarction complicated with Graves' disease. She had right
      sided hemiparesis that deteriorated on day 8 with the infarct growth and
      thyrotoxicosis. On angiogram, the left MCA was occluded at the origin without
      moyamoya vessels. Positron emission tomography (PET) revealed misery-perfusion
      phenomenon in the left MCA territory. After initiation of the antithyroid
      therapy, her hemiparesis became milder. Seventeen months later, her thyroid
      function was normalized and net-like collateral moyamoya vessels proliferated in
      the left MCA territory. Misery-perfusion phenomenon persisted on PET. This report
      is unique in the point of neurologic recovery of the moyamoya patient right after
      initiation of antithyroid medication without radiological improvement. 

PMID- 24119626
TI  - Self-reported sleep duration in relation to incident stroke symptoms: nuances by
      body mass and race from the REGARDS study.
AB  - BACKGROUND: To determine, among employed persons with low risk for obstructive
      sleep apnea (OSA), if sleep duration is associated with incident stroke symptoms,
      independent of body mass index (BMI), and if sleep duration mediates racial
      differences in stroke symptoms. METHODS: In 2008, 5666 employed participants (US
      blacks and whites, >=45 years) from the longitudinal and nationally
      representative Reasons for Geographic And Racial Differences in Stroke study self
      reported their average sleep duration. Participants had no history of stroke,
      transient ischemic attack, or stroke symptoms and were at low risk for OSA. After
      the sleep assessment, self-reported stroke symptoms were collected at 6-month
      intervals, up to 3 years (M = 751 days). Interval-censored, parametric survival
      models were conducted to estimate hazard ratios predicting time from sleep
      duration measurement (<6, 6-6.9, 7-7.9 [reference], 8-8.9, >=9 hours) to first
      stroke symptom. Adjusted models included demographics, stroke risk factors,
      psychological symptoms, health behaviors, and diet. RESULTS: During follow-up,
      224 participants reported 1 or more stroke symptoms. In the unadjusted model,
      short sleep (<6 hours) significantly predicted increased risk of stroke symptoms
      but not in adjusted models. Stratification by BMI revealed a significant
      association between short sleep duration and stroke symptoms only for normal BMI
      persons in unadjusted (hazard ratio: 2.93, 95% confidence interval: 1.38-6.22)
      and fully adjusted models (hazard ratio: 4.19, 95% confidence interval: 1.62
      10.84). The mediating effect of sleep duration on the relationship between race
      and stroke symptoms was borderline significant in normal weight participants.
      CONCLUSIONS: Among middle-aged to older employed individuals of normal weight and
      low risk of OSA, self-reported short sleep duration is prospectively associated
      with increased risk of stroke symptoms.

PMID- 24119627
TI  - Ruptured aneurysm of the PICA communicating artery: a case report.
AB  - A 47-year-old man presented with a rare aneurysm arising from the posterior
      inferior cerebellar artery communicating artery (PICA com A), manifesting as
      subarachnoid with intraventricular hemorrhage. Cerebral angiography showed a
      defect of the left PICA, and the left PICA region was supplied by a communicating
      artery formed by the fusion of branches from the right PICA and right vertebral
      artery. Aneurysms arose in the communicating artery, and a small, unruptured
      fusiform aneurysm was observed adjacent to a ruptured aneurysm. Trapping was
      performed for the 2 aneurysms with occipital artery (OA)-PICA bypass. Six cases
      of aneurysms occurring in this vessel including ours have been reported, and
      hemodynamic factors and congenital fragility of the arterial wall have been
      suggested as causative factors. Ours is the first case in which a ruptured
      aneurysm of this vessel was treated surgically with concurrent vascular
      reconstruction. If the aneurysm has a shape that is difficult to clip, the
      affected vessel is difficult to preserve, and collateral blood flow to the
      affected PICA region is considered insufficient, trapping with OA-PICA bypass is
      recommended. 

PMID- 24119629
TI  - Discrimination of acute ischemic stroke from nonischemic vertigo in patients
      presenting with only imbalance.
AB  - Some patients who present with an acute feeling of imbalance are experiencing an
      ischemic stroke that is not evident on computed tomography (CT) scans. The aim of
      this study was to compare ischemic stroke and nonischemic vertigo patient groups
      and to investigate independent factors associated with ischemic stroke. We
      examined 332 consecutive patients with an acute feeling of imbalance who showed
      no neurologic findings or responsible lesions on CT scan at the hyperacute phase.
      We examined their clinical backgrounds, physical findings, and laboratory
      examinations, with ischemic stroke diagnosed by later CT and/or magnetic
      resonance imaging (MRI). We identified 41 (12.3%) ischemic stroke patients.
      Atrial fibrillation (odds ratio 4.1; 95% confidence interval 1.4-11.5), white
      blood cell count (10(3)/MUL, 1.4; 1.2-1.6), head and/or neck pain (4.6; 2.1
      10.3), first attack of imbalance feeling (3.3; 1.1-12.2), and dizziness (3.7; 1.7
      8.3) were significant and independent factors associated with ischemic stroke
      among patients with an acute feeling of imbalance. We used these factors to
      calculate an "imbalance score"; 1 point was given for the presence of each factor
      and a score of 3-5 points was independently associated with ischemic stroke. An
      awareness of these factors may indicate that further examinations including MRI
      are necessary to rule out ischemic stroke. 

PMID- 24119628
TI  - Internal cerebral vein asymmetry on follow-up brain computed tomography after
      intravenous thrombolysis in acute anterior circulation ischemic stroke is
      associated with poor outcome.
AB  - BACKGROUND: Identifying early predictors of functional outcome after acute
      ischemic stroke (AIS) is important for planning rehabilitation strategies.
      Internal cerebral veins (ICV) drain deep parts of brain, run parallel to each
      other, and consistently seen on computed tomography angiography (CTA). Even minor
      asymmetry in their filling can be identified. We hypothesized that venous
      drainage would be impaired in patients with acute occlusion of internal carotid
      artery or middle cerebral artery. Because systemic thrombolysis can alter the
      vascular findings, we evaluated the relationship between ICV asymmetry on follow
      up CTA and functional outcome. METHODS: Consecutive AIS patients treated with
      intravenous thrombolysis between 2007 and 2010 were included. ICV asymmetry was
      assessed by 2 independent blinded stroke neurologists/neuroradiologists.
      Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months,
      dichotomized as good (0-1) and poor (2-6). Data were analyzed for predictors of
      functional outcome. RESULTS: Of 2238 patients with AIS, 226 (10.1%) anterior
      circulation AIS patients received intravenous thrombolysis. The median age was 65
      years (range 19-92), 44% were men, and median National Institutes of Health
      Stroke Scale (NIHSS) score was 16 points (range 4-32). Hypertension was the
      commonest risk factor in 173 (76.5%) patients, whereas 78 (34.5%) had atrial
      fibrillation. ICV asymmetry on follow-up CTA was assessed in 103 (45.5%)
      patients. Admission NIHSS score (odds ratio [OR] 1.07; 95% confidence interval
      [CI] 1.079-1.201, P = .046), change in NIHSS score during first 24 hours (OR
      .737; 95% CI .672-.807, P < .0001), and ICV asymmetry on follow-up CTA (OR 20.3;
      95% CI 4.67-52.07, P < .0001) independently predicted poor outcome at 3 months.
      CONCLUSIONS: ICV asymmetry on follow-up CTA after intravenous thrombolysis is an
      early predictor of poor functional outcome.

PMID- 24119630
TI  - A blood-based biomarker panel to detect acute stroke.
AB  - BACKGROUND: The aim of this study was to develop an adjunctive, peripheral
      biomarker test to differentiate ischemic strokes, intracranial hemorrhages
      (ICHs), and stroke mimics in the acute setting. METHODS: Serum samples were
      collected from 167 patients who presented with an acute neurologic deficit within
      24 hours of symptom onset. Patients were adjudicated to ischemic stroke, ICH, and
      mimic pathology groups based on clinical and radiographic findings. Samples were
      tested for levels of 262 potential markers. A multivariate Cox proportional
      hazards regression model of 5 biomarkers was built by stepwise selection and
      validated by bootstrapping. Its discriminative capacity was quantified by C index
      and net reclassification improvement (NRI). RESULTS: The final model consisted of
      eotaxin, epidermal growth factor receptor, S100A12, metalloproteinase inhibitor
      4, and prolactin. It demonstrated a discriminative capacity for ischemic stroke
      versus mimic (C = .92), ischemic stroke and ICH versus mimic (C = .93), and
      ischemic stroke versus ICH (C = .82). The inclusion of biomarkers to a model
      consisting of age, race, and gender resulted in an NRI of 161% when detecting
      ischemic stroke versus mimic (P < .0001), an improvement of 171% when detecting
      ischemic strokes plus ICH versus mimic (P < .0001), and an improvement of 56%
      when detecting ischemic strokes versus ICH (P = .1419). CONCLUSIONS: These
      results suggest that information obtained from a 5-biomarker panel may add
      valuable information in the early evaluation and management of patients with
      stroke-like symptoms.

PMID- 24119631
TI  - Systematic review of the efficacy and tolerability of clozapine in the treatment
      of youth with early onset schizophrenia.
AB  - BACKGROUND: The use of clozapine (CLZ) for treatment-resistant schizophrenia is
      well established in adults. However, it is seldom used in youth with early onset
      schizophrenia (EOS) largely because of lack of clarity about its risk benefit
      ratio. This review synthesises and evaluates available evidence regarding the
      efficacy and tolerability of CLZ in EOS with the aim to assist clinical decision
      making. METHODS: We conducted a systematic review of the primary literature on
      the clinical efficacy and adverse drug reactions (ADRs) observed during CLZ
      treatment in EOS. We also identified relevant practice guidelines and summarised
      current guidance. RESULTS: CLZ showed superior efficacy than other antipsychotics
      in treating refractory EOS patients; short-term clinical trials suggest an
      average improvement of 69% on the Brief Psychiatric Rating Scale that was
      sustained during long-term follow-up (up to 9 years). No fatalities linked to CLZ
      treatment were reported. Sedation and hypersalivation were the most common
      complaints, reported by over 90% of patients. Other common ADRs (reported in 10
      60% of patients) were enuresis, constipation, weight gain, and non-specific EEG
      changes. Less common ADRs (reported in 10-30% of patients) were akathisia,
      tachycardia and changes in blood pressure. Neutropenia was reported in 6-15% of
      cases but was usually transient while agranulocytosis was rare (<0.1%). Seizures
      were also uncommon (<3%). Metabolic changes were relatively common (8-22%) but
      emergent diabetes was not frequently observed (<6%). Overall the rate of
      discontinuation was low (3-6%). Current guidelines recommend the use of CLZ in
      EOS patients who have failed to respond to two adequate trials with different
      antipsychotics and provide detailed schedules of assessments to evaluate and
      assess potential ADRs both prior to initiation and throughout CLZ treatment.
      CONCLUSION: Available data although limited in terms of number of studies are
      consistent in demonstrating that CLZ is effective and generally safe in the
      treatment of refractory EOS provided patients are regularly monitored.

PMID- 24119632
TI  - Phytotherapy in urology. Current scientific evidence of its application in benign
      prostatic hyperplasia and prostate adenocarcinoma.

PMID- 24119633
TI  - Incidence of positive surgical margins after robotic assisted radical
      prostatectomy: Does the surgeon's experience have an influence on all
      pathological stages?
AB  - OBJECTIVE: The aim of this study is to analyze the clinical and surgical features
      of patients who underwent robotic-assisted radical prostatectomy (RARP) at our
      institution, and the impact of the surgeon's experience in the oncological
      results related to pathological stage. MATERIAL AND METHODS: An analysis of 300
      RARP consecutively performed by the same urologist was conducted. Patients were
      divided into 3 groups of 100 patients in chronological order, according to
      surgery date. All patients had organ-confined clinical stage. Variables which
      could impact in positive margins rates were analyzed. Finally, positive surgical
      margins (PSM) in regard to pathological stage and surgeon's experience were
      compared and analyzed. RESULTS: No significant differences were found in
      variables which could impact in PSM rates. The overall PSM rate was 21%, with 28%
      in the first group, 20% in the second, and 16% in the third (P = .108).
      Significant lineal decreasing tendency was observed (P = .024). In pT2 patients,
      the overall PSM rate was 16.6%, with 27%, 13.8%, and 7.3% in each group
      respectively (P = .009). A significant difference was found between group 1 and
      group 3 (P = .004). In pT3 patients, the surgeon's experience was not
      significantly associated with margin reductions with an overall PSM rate of 27.7%
      (28.2%, 28.6%, and 26.7% in each group respectively). CONCLUSIONS: Clinical and
      surgical features in our patients did not vary over time. We found a significant
      reduction of PSM related to surgeon's experience in pT2 patients. Contrariwise,
      the margin status remained stable despite increasing experience in pT3 patients.

PMID- 24119634
TI  - Reply to "Phytotherapy in urology. Current scientific evidence of its application
      in benign prostatic hyperplasia and prostate adenocarcinoma".

PMID- 24119636
TI  - Why are membrane targets discovered by phenotypic screens and genome sequencing
      in Mycobacterium tuberculosis?
AB  - High through put screening (HTS) was extensively used in attempts to discover new
      TB drugs from libraries of pure small molecule compounds many of which complied
      with the rule of five. Coupled with new methods for determining the target of
      lead compounds by resistance selection followed by genome sequencing, screening
      for growth inhibitors led to several recent reports of compounds linked to
      specific antitubercular targets. This systematic approach to drug discovery
      appears at present to select for small, hydrophobic molecules affecting the
      function of essential membrane proteins, for example DprE, MmpL3, AtpE, QcrB, and
      Pks13. All of these molecules possessed bactericidal activity in vitro. Mutations
      in GlpK were also selected with hydrophobic compounds identified by screening for
      growth inhibitors. The chemical properties of the compounds reported are
      considered in the context of uptake and possible mechanisms of inhibition of
      membrane bound targets based on other model systems (e.g. cardiovascular drugs
      affecting voltage-gated L-type calcium channels, daptomycin, telavancin,
      gramicidin S, and role of boundary lipids). The relationship between
      hydrophobicity, compound uptake, and mode of action are addressed. Compared to
      the average calculated logP for approved TB drugs of -1.0, the average for these
      hydrophobic compounds is 4.0 representing a major shift in hydrophobicity of 5
      orders of magnitude. Furthermore several hydrophobic compounds in the Prestwick
      Chemical Library (FDA approved drugs) inhibit growth of M. tuberculosis at 10
      MUg/ml or less and have an average calculated logP of 5.7 signaling caution with
      respect to specificity. Key recommendations are made regarding follow-up of the
      hydrophobic leads recently discovered using phenotypic screening and target
      elucidation by genome sequencing. Consideration is also given to the properties
      of small molecule screening libraries, the types of molecules and targets
      recently discovered as antitubercular leads and compliance with the rule of 5. 

PMID- 24119635
TI  - Sizing the association between lifestyle behaviours and fatness in a large,
      heterogeneous sample of youth of multiple ethnicities from 4 countries.
AB  - BACKGROUND: The magnitude of the relationship between lifestyle risk factors for
      obesity and adiposity is not clear. The aim of this study was to clarify this in
      order to determine the level of importance of lifestyle factors in obesity
      aetiology. METHODS: A cross-sectional analysis was carried out on data on youth
      who were not trying to change weight (n = 5714), aged 12 to 22 years and from 8
      ethnic groups living in New Zealand, Australia, Fiji and Tonga. Demographic and
      lifestyle data were measured by questionnaires. Fatness was measured by body mass
      index (BMI), BMI z-score and bioimpedance analysis, which was used to estimate
      percent body fat and total fat mass (TFM). Associations between lifestyle and
      body composition variables were examined using linear regression and forest
      plots. RESULTS: TV watching was positively related to fatness in a dose-dependent
      manner. Strong, dose-dependent associations were observed between fatness and
      soft drink consumption (positive relationship), breakfast consumption (inverse
      relationship) and after-school physical activity (inverse relationship).
      Breakfast consumption-fatness associations varied in size across ethnic groups.
      Lifestyle risk factors for obesity were associated with percentage differences in
      body composition variables that were greatest for TFM and smallest for BMI.
      CONCLUSIONS: Lifestyle factors were most strongly related to TFM, which suggests
      that studies that use BMI alone to quantify fatness underestimate the full effect
      of lifestyle on adiposity. This study clarifies the size of lifestyle-fatness
      relationships observed in previous studies.

PMID- 24119637
TI  - The effect of levels and types of experience on judgment of synthesized voice
      quality.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to determine the effect of
      level and type of experience on the judgment of voice quality and to examine the
      correlation among acoustical measurements and perceptions of voice quality. STUDY
      DESIGN: This was a within-subjects group design. METHODS: Speech-language
      pathologists, singing voice teachers (SVTs), speech-language pathology graduate
      students with and without experience with a voice client, graduate students who
      have completed a voice pedagogy course, and inexperienced listeners (IEs) rated
      stimuli with systematically altered measurements of jitter, shimmer, and noise-to
      harmonics ratio (NHR) on a visual analog scale ranging from mild to severe for
      overall severity, roughness, breathiness, strain, and pitch. RESULTS: Results
      showed that the type of experience had an impact on judgments of voice quality
      more than the level of experience. Also, jitter/shimmer combination stimuli and
      shimmer only stimuli frequently correlated with the ratings of overall severity,
      roughness, and strain, and NHR stimuli correlated with ratings of breathiness
      across all groups. Only IEs, SVTs, and their students had significant
      correlations for ratings of pitch with jitter/shimmer combination stimuli having
      the highest correlations. CONCLUSION: The conclusion was that the level and type
      of experience affect judgments of voice quality.

PMID- 24119638
TI  - Vocal fold vibration after photofrin-mediated photodynamic therapy for treatment
      of early-stage laryngeal malignancies.
AB  - OBJECTIVE/HYPOTHESIS: To analyze vocal fold vibration after photofrin-mediated
      photodynamic therapy (PDT) for the treatment of Tis and T1N0M0 squamous cell
      carcinoma (SqCCa) tumors of the larynx. It was hypothesized that key attributes
      of vocal fold vibration would return to baseline within 1-6 months of treatment.
      STUDY DESIGN: Retrospective. METHODS: Laryngovideostroboscopic data were
      retrospectively analyzed for eight patients with Tis-T1N0M0 SqCCa tumors of the
      larynx treated with photofrin-mediated PDT. Baseline and posttreatment
      videostroboscopy images of select vibratory characteristics of the vocal folds
      were randomized and analyzed by a speech-language pathologist and fellowship
      trained laryngologist specializing in voice disorders. RESULTS: Significant
      improvement in mucosal wave (P=0.003) and amplitude of vibration (P=0.004)
      occurred at greater than or equal to 20 weeks post-PDT compared with baseline.
      Comparing results within 5 weeks postprocedure to 10-19-weeks postprocedure
      revealed significant improvement in amplitude of vibration (P=0.013) and
      nonvibrating portion of the vocal fold (P=0.020). Comparing results within 5
      weeks postprocedure to 20 or more weeks postprocedure revealed significant
      improvement in amplitude of vibration (P=0.001), mucosal wave (P=0.001), and
      nonvibrating portion of the effected fold (P=0.001). CONCLUSION: Photofrin
      mediated PDT allows for preservation of function and structure of the larynx
      without systemic toxicity; however, it may take 4-5 months or more for key
      vibratory characteristics of the vocal folds to recover posttreatment.

PMID- 24119639
TI  - Factors associated with singers' perceptions of choral singing well-being.
AB  - OBJECTIVES: Choral singing is a popular vocational pastime across cultures. The
      potential health benefits associated with choral singing, including positive
      effect on well-being, are a topic of interest in health research. However,
      anecdotal reports from voice professionals suggest that the unique demands of
      choral singing may enforce unhealthy singing habits. This study explores
      suboptimal vocal behaviors that are sometimes associated with choral singing,
      which include singing outside comfortable pitch range, singing too loudly, and
      singing too softly for blend. METHOD: The relationships between suboptimal choral
      singing habits, vocal warm-ups (WUs), vocal fatigue, and singing-related well
      being were assessed via a 14-item Likert-based response format questionnaire.
      Participants consisted of 196 attendees of the international World Choir Games.
      The final study group consisted of 53 male and 143 female international amateur
      singers aged 10-70. RESULTS: Results indicated a positive correlation between
      vocal fatigue and suboptimal singing behaviors (r = 0.34, P < 0.0001).
      Participants who did not engage in suboptimal singing behavior experienced
      increased singing-related well-being (r = -0.32, P < 0.0001, N = 141). Vocal WUs
      were not related to vocal fatigue or singing well-being. Substantially, more
      participants from this demographic preferred choir over solo singing (X2[1, N =
      196] = 22.93, P < 0.0001). CONCLUSION: Suboptimal choral singing behaviors may
      result in vocal fatigue and reduction of choral singing well-being and should
      therefore be considered when examining the effect of choral singing on singing
      related well-being and health. Future research will compare the amateurs'
      perceptions of choral singing with perceptions from professional singers and will
      look at determinants of choral singing well-being.

PMID- 24119640
TI  - Efficacy of intensive phonatory-respiratory treatment (LSVT) for presbyphonia:
      two case reports.
AB  - OBJECTIVES: Research evidence has shown that neither traditional voice therapy
      nor surgery was efficacious in managing age-related dysphonia, specifically for
      more severe cases with pronounced fold atrophy or larger glottal gaps. The
      purpose of this study was to examine the efficacy of intensive respiratory
      phonatory treatment (Lee Silverman voice treatment [LSVT]) for glottal
      incompetence associated with presbyphonia. STUDY DESIGN: Nonrandomized
      prospective study. METHODS: Two subjects with age-related vocal fold bowing
      received 4 weeks of the LSVT. Strobolaryngoscopic examination, phonatory function
      measurement, acoustical analyses, and perceptual judgments of voice were obtained
      at baseline and 2 weeks posttreatment. Additional acoustic measures of phonatory
      function, including vocal intensity, maximum phonation time, and pitch range,
      were also obtained during 16 treatment sessions. RESULTS: Both subjects exhibited
      significant improvements in glottal closure, phonatory function, acoustic
      features, and perceptual ratings of voice after treatment. Significant changes of
      phonatory function measures were noticed relatively early and remained steady
      throughout the course of treatment. CONCLUSIONS: These findings provide solid
      evidence that speakers with age-related vocal fold bowing and dysphonia may
      improve glottal competence and related vocal function with neither laryngeal
      trauma nor maladaptive laryngeal hyperfunction after the LSVT.

PMID- 24119641
TI  - Immediate effects of the Finnish resonance tube method on behavioral dysphonia.
AB  - OBJECTIVE: To investigate the immediate effects of the Finnish resonance tube
      method for teachers with behavioral dysphonia. METHODS: Twenty-five female
      teachers (m=39.9 years of age) with at least a 5-year history of dysphonia were
      included. Additional inclusion criteria were the diagnosis of chronic behavioral
      dysphonia with an indication for speech therapy and the absence of any prior
      speech therapy. Subjects produced three sets of 10 tokens of sustained phonation
      with a 1-minute rest interval between tokens into a 27-cm glass tube immersed in
      at least 2 cm of water. Voice samples were recorded before and after these sets.
      The effects of these exercises were evaluated by self-assessment, auditory
      perceptual analysis, and acoustic evaluation involving extraction of fundamental
      frequency and visual spectrographic analysis. RESULTS: Sixty-eight percent of the
      teachers reported increased phonatory comfort and 52% reported improved voice
      quality after performing the exercises. Perceptual analysis indicated improved
      voice quality in the samples of counting numbers, confirmed by decreased
      instability, subharmonics, noise in high frequencies, and the tendency for
      reduced low frequency noise on spectrographic evaluation. Additionally, mean
      fundamental frequency decreased. CONCLUSION: The Finnish resonance tube method
      increased phonatory comfort and vocal changes suggestive diminished
      hyperfunction.

PMID- 24119642
TI  - Pediatric arytenoid dislocation: diagnosis and treatment.
AB  - Arytenoid dislocation and subluxation are well-described injuries in adults but
      are poorly documented in children. The most commonly cited etiology is intubation
      trauma although external blunt trauma also is recognized. Symptoms include
      dysphonia, vocal fatigue, loss of vocal control, breathiness, odynophagia,
      dysphagia, dyspnea, and cough. Prompt diagnosis and treatment lead to the best
      chance for recovery, and delayed treatment is likely to result in scarring and
      possibly ankylosis. The mean age of our study group was 12.3 years and consisted
      of six males (55%) and five females (45%). The most commonly presenting symptom
      was hoarseness (81.8%). Six of the 11 patients underwent surgical correction of
      the dislocated arytenoid cartilage. Four patients refused any treatment and one
      patient received voice therapy alone. Two patients who refused surgical
      intervention had spontaneous reduction of their dislocations. After surgical
      intervention, one patient regained normal voice, four patients had substantial
      voice improvement without return to preinjury vocal function, and one patient had
      only slight voice improvement. Pediatric symptoms are similar to these in adults,
      yet these may be less noticeable to the patient and clinician. A high index of
      suspicion is needed to diagnose and treat pediatric arytenoid dislocation. 

PMID- 24119643
TI  - Three-dimensional reconstruction of human vocal folds and standard laryngeal
      cartilages using computed tomography scan data.
AB  - Three-dimensional (3D) computer models of the human larynx are useful tools for
      research and for eventual clinical applications. Recently, computed tomography
      (CT) scanning and magnetic resonance imaging (MRI) have been used to recreate
      realistic models of human larynx. In the present study, CT images were used to
      create computer models of vocal folds, vocal tract, and laryngeal cartilages, and
      the procedure to create solid models are explained in details. Vocal fold and
      vocal tract 3D models of healthy and postsurgery larynges during phonation and
      respiration were created and morphometric parameters were quantified. The
      laryngeal framework of eight patients was also reconstructed from CT scan images.
      For each cartilage, morphometric landmarks were measured on the basis of their
      importance for biomechanical modeling. A quantitative comparison was made between
      measured values from the reconstructions and those from human excised larynges in
      literature. The good agreement between these measurements supports the accuracy
      of CT scan-based 3D models. Generic standard models of the laryngeal framework
      were created using known features in modeling softwares. They were created based
      on the morphometric landmark dimensions previously defined, preserving all
      biomechanically important dimensions. These models are accessible, subject
      independent, easy to use for computational simulations, and make the comparisons
      between different studies possible. 

PMID- 24119644
TI  - Test-retest reliability for aerodynamic measures of voice.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the
      intrasubject reliability of aerodynamic characteristics of the voice within
      typical/normal speakers across testing sessions using the Phonatory Aerodynamic
      System (PAS 6600; KayPENTAX, Montvale, NJ). METHODS: Participants were 60 healthy
      young adults (30 males and 30 females) between the ages 18 and 31 years with
      perceptually typical voice. Participants were tested using the PAS 6600
      (Phonatory Aerodynamic System) on two separate days with approximately 1 week
      between each session at approximately the same time of day. Four PAS protocols
      were conducted (vital capacity, maximum sustained phonation, comfortable
      sustained phonation, and voicing efficiency) and measures of expiratory volume,
      maximum phonation time, mean expiratory airflow (during vowel production) and
      target airflow (obtained via syllable repetition), peak air pressure, aerodynamic
      power, aerodynamic resistance, and aerodynamic efficiency were obtained during
      each testing session. Associated acoustic measures of vocal intensity and
      frequency were also collected. All phonations were elicited at comfortable pitch
      and loudness. RESULTS: All aerodynamic and associated variables evaluated in this
      study showed useable test-retest reliability (ie, intraclass correlation
      coefficients [ICCs] >= 0.60). A high degree of mean test-retest reliability was
      found across all subjects for aerodynamic and associated acoustic measurements of
      vital capacity, maximum sustained phonation, glottal resistance, and vocal
      intensity (all with ICCs > 0.75). Although strong ICCs were observed for measures
      of glottal power and mean expiratory airflow in males, weaker overall results for
      these measures (ICC range: 0.60-0.67) were observed in females subjects and
      sizable coefficients of variation were observed for measures of power,
      resistance, and efficiency in both men and women. Differences in degree of
      reliability from measure to measure were revealed in greater detail using methods
      such as ICCs and coefficients of variation than with means comparison testing.
      The results of this study also show that reliable aerodynamic and associated
      measures may be elicited using comfortable pitch and loudness. CONCLUSIONS: The 1
      week test-retest reliability for the majority of aerodynamic and associated
      acoustic measures assessed in this study is considered good-to-excellent.
      Clinicians and researchers using aerodynamic and associated measures should be
      aware of possible significant gender effects that influence both normative
      expectations as well as the standard error of measurement (ie, typical error) and
      estimates of minimum difference that may be used to differentiate typical from
      disordered voice.

PMID- 24119645
TI  - A xeno-free culture method that enhances Wharton's jelly mesenchymal stromal cell
      culture efficiency over traditional animal serum-supplemented cultures.
AB  - BACKGROUND AIMS: Mesenchymal stromal cell (MSC) transplantation holds great
      promise for use in medical therapies. Several key features of MSCs, including
      efficient cell growth, generation of sufficient cell numbers and safety, as
      determined by teratoma formation, make MSCs an ideal candidate for clinical use.
      However, MSCs derived under standard culture conditions, co-cultured with animal
      by-products, are inappropriate for therapy because of the risks of graft
      rejection and animal virus transmission to humans. Alternative serum sources have
      been sought for stem cell production. METHODS: We demonstrate for the first time
      that human serum from umbilical cord blood (hUCS) is an effective co-culture
      reagent for MSC production from Wharton's jelly MSCs (WJMSCs). Ten umbilical
      cords were used to generate parallel cultures of WJMSC lines under medium
      supplemented with hUCS and embryonic stem cell-qualified fetal bovine serum. The
      WJMSC lines from each medium were analyzed and compared with regard to cell line
      derivation, proliferation ability and characteristic stability. RESULTS: The
      phenotypic characteristics of WJMSC derived under either medium showed no
      differences. WJMSC lines derived under hUCS medium displayed comparable primary
      culture cell outgrowth, lineage differentiation capacity and cell recovery after
      cryopreservation compared with supplementation with embryonic stem cell-qualified
      fetal bovine serum medium. However, superior cell proliferation rates and
      retention of in vitro propagation (>22 passages) were observed in WJMSC cultures
      supplemented with hUCS. Additionally, more robust population doubling times were
      observed in hUCS-supplemented cultures. CONCLUSIONS: We conclude that hUCS is an
      efficient and effective serum source for animal product-free WJMSC line
      production and can generate MSC lines that may be appropriate for therapeutic
      use.

PMID- 24119646
TI  - Protective effects of mesenchymal stromal cells on adriamycin-induced minimal
      change nephrotic syndrome in rats and possible mechanisms.
AB  - BACKGROUND AIMS: Minimal change nephrotic syndrome is the most frequent cause of
      nephrotic syndrome in childhood. Current treatment regimes, which include
      glucocorticoid hormones and immunosuppressive therapy, are effective and have
      fast response. However, because of the side effects, long treatment course, poor
      patient compliance and relapse, novel approaches for the disease are highly
      desired. METHODS: The adriamycin-induced nephrotic rat model was established.
      Rats were allocated to a model group, a prednisone group or mesenchymal stromal
      cell (MSC) group. Clinical parameters in each treatment group were determined at
      2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin,
      p21 and monocyte chemoattractant protein-1 were determined through the use of
      quantitative real-time-polymerase chain reaction. Protein levels were determined
      by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were
      isolated and apoptotic rate after adriamycin with or without MSC treatment was
      analyzed by means of flow cytometry. RESULTS: MSC intervention improved renal
      function as assessed by urinary protein, blood creatinine and triglyceride
      levels. MSC intervention reduced adriamycin-induced renal tissue damage
      visualized by immunohistochemistry and light and electron microscopic analysis
      and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA
      and protein levels of synaptopodin and p21 in renal cortex were significantly
      increased. MSCs also restored synaptopodin mRNA and protein expression in
      isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal
      cortex and protein level in serum of the MSC treatment group were significantly
      decreased compared with that in the adriamycin-induced nephropathy model group.
      CONCLUSIONS: Our data indicate that MSCs could protect rats from adriamycin
      induced minimal change nephrotic syndrome, and the protective effects of MSCs are
      mediated through multiple actions.

PMID- 24119647
TI  - Functional potentials of human hematopoietic progenitor cells are maintained by
      mesenchymal stromal cells and not impaired by plerixafor.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) resemble an essential component
      of the bone marrow niche for maintenance of stemness of hematopoietic progenitor
      cells (HPCs). Perturbation of the C-X-C chemokine receptor type 4 (CXCR4)/stromal
      cell-derived factor-1alpha (SDF-1alpha) axis by plerixafor (AMD3100) mobilizes
      HPCs from their niche; however, little is known about how plerixafor affects
      interaction of HPCs and MSCs in vitro. METHODS: We monitored cell division
      kinetics, surface expression of CD34 and CXCR4, migration behavior and colony
      forming frequency of HPCs on co-culture with MSCs either with or without exposure
      to plerixafor. RESULTS: Co-culture with MSCs significantly accelerated cell
      division kinetics of HPCs. Despite this, the proportion of CD34+ cells was
      significantly increased on co-culture, whereas the expression of CXCR4 was
      reduced. In addition, co-culture with MSCs led to significantly higher colony
      forming capacity and enhanced migration rate of HPCs compared with mono-culture
      conditions. The composition of MSC sub-populations-and conversely their
      hematopoiesis supportive functions-may be influenced by culture conditions. We
      compared the stromal function of MSCs isolated with three different culture
      media. Overall, the supporting potentials of these MSC preparations were quite
      similar. Perturbation by the CXCR4-antagonist plerixafor reduced the cell
      division kinetics of HPCs on co-culture with MSCs. However, the progenitor cell
      potential of the HPCs as reflected by colony-forming capacity was not affected by
      plerixafor. CONCLUSIONS: These results support the notion that the CXCR4/SDF
      1alpha axis is critical for HPC-MSC interaction with regard to migration,
      adhesion and regulation of proliferation but not for maintenance of primitive
      progenitor cells.

PMID- 24119648
TI  - Syngeneic adipose-derived stem cells with short-term immunosuppression induce
      vascularized composite allotransplantation tolerance in rats.
AB  - BACKGROUND AIMS: A clinically applicable tolerance induction regimen that removes
      the requirement for lifelong immunosuppression would benefit recipients of
      vascularized composite allotransplantation (VCA). We characterized the
      immunomodulatory properties of syngeneic (derived from the recipient strain)
      adipocyte-derived stem cells (ADSCs) and investigated their potential to induce
      VCA tolerance in rats. METHODS: ADSCs were isolated from Lewis (LEW, RT1A(l))
      rats; their immunomodulatory properties were evaluated by means of mixed
      lymphocyte reactions in vitro and VCAs in vivo across a full major
      histocompatibility complex mismatch with the use of Brown-Norway (BN, RT1A(n))
      donor rats. Two control and four experimental groups were designed to evaluate
      treatment effects of ADSCs and transient immunosuppressants (anti-lymphocyte
      globulin, cyclosporine) with or without low-dose (200 cGy) total body
      irradiation. Flow cytometry was performed to quantify levels of circulating
      CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). RESULTS: Cultured syngeneic
      ADSCs exhibited CD90.1(+)CD29(+)CD73(+)CD45(-)CD79a(-)CD11b/c(-) phenotype and
      the plasticity to differentiate to adipocytes and osteocytes. ADSCs dramatically
      suppressed proliferation of LEW splenocytes against BN antigen and mitogen,
      respectively, in a dose-dependent fashion, culminating in abrogation of allo- and
      mitogen-stimulated proliferation at the highest concentration tested.
      Accordingly, one infusion of syngeneic ADSCs markedly prolonged VCA survival in
      LEW recipients treated with transient immunosuppression; of these, 66% developed
      tolerance. Total body irradiation provided no additional VCA survival benefit. An
      important role for Tregs in tolerance induction/maintenance was suggested in vivo
      and in vitro. CONCLUSIONS: Treatment comprising syngeneic ADSCs and transient
      immunosuppression (i) increased levels of circulating Tregs and (ii) induced
      tolerance in 66% of recipients of major histocompatibility complex-mismatched
      VCAs.

PMID- 24119649
TI  - Characterization and evaluation of the differentiation ability of human adipose
      derived stem cells growing in scaffold-free suspension culture.
AB  - BACKGROUND AIMS: Human adipose-derived stem cells (hADSCs) have become a popular
      stem cell source because of their abundant supplies, high differentiation ability
      and the fact that they present few ethical concerns. Suspension culture, a type
      of three-dimensional culture, is a more suitable model for mimicking cell-cell
      and cell-extracellular matrix interactions than is two-dimensional monolayer
      culture. The aim of this study was to determine the effects of suspension culture
      on the viability and differentiation potential of hADSCs. METHODS: Different
      densities of hADSCs were cultured in ultra-low-attachment surface plates. The
      morphology and mean diameter of the resultant aggregates were determined by means
      of microscopy. The viability of the aggregates was evaluated with the use of 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, inner salt, lactate dehydrogenase and live/dead assays. To detect
      osteogenesis, chondrogenesis and adipogenesis in hADSCs in suspension culture,
      cell aggregates were stained to determine cell function, and the expression of
      specific markers was evaluated through the use of real-time reverse transcriptase
      polymerase chain reaction. RESULTS: The hADSCs remained viable in suspension
      culture and formed cell aggregates. The diameter of the majority of the
      aggregates was in the range of 50-200 MUm, regardless of cell density. The
      aggregation of the hADSCs served to maintain cell survival. In addition, the
      results of the histomorphometric and gene expression analyses showed that the
      hADSCs were more efficiently induced to differentiate into osteoblasts,
      chondrocytes and adipocytes in suspension culture than in two-dimensional
      monolayer culture. CONCLUSIONS: Suspension culture can be used to maintain cell
      viability and contributes to the effective differentiation of hADSCs, providing
      an alternative cell growth strategy for application to stem cell-based
      regenerative medicine.

PMID- 24119650
TI  - Biomarkers predicting sepsis in polytrauma patients: Current evidence.
AB  - INTRODUCTION: Major trauma still represents one of the leading causes of death in
      the first four decades of life. Septic complications represent the predominant
      causes of late death (45% of overall mortality) in polytrauma patients. The
      ability of clinicians to early differentiate between systemic inflammatory
      response syndrome (SIRS) and sepsis is demonstrated to improve clinical outcome
      and mortality. The identification of an "ideal" biomarker able to early recognize
      incoming septic complications in trauma patients is still a challenge for
      researchers. AIM: To evaluate the existing evidence regarding the role of
      biomarkers to predict or facilitate early diagnosis of sepsis in trauma patients,
      trying to compile some recommendations for the clinical setting. METHODS: An
      Internet-based search of the MEDLINE, EMBASE and Cochrane Library databases was
      performed using the search terms: "Biomarkers", "Sepsis" and "Trauma" in various
      combinations. The methodological quality of the included studies was assessed
      using the Quality Assessment of Diagnostic Accuracy Studies Checklist (QUADAS).
      After data extraction, the level of evidence available for each bio-marker was
      rated and presented using the "best-evidence synthesis" method, in line with the
      US Agency for Healthcare Research and Quality. RESULTS: Thirty studies were
      eligible for the final analysis: 13 case-control studies and 17 cohort studies.
      The "strong evidence" available demonstrated the potential use of procalcitonin
      as an early indicator of post-traumatic septic complications and reported the
      inability of c-reactive protein (CRP) to specifically identify infective
      complications. Moderate, conflicting and limited evidence are available for the
      other 31 biomarkers. CONCLUSION: Several biomarkers have been evaluated for
      predicting or making early diagnosis of sepsis in trauma patients. Current
      evidence does not support the use of a single biomarker in diagnosing sepsis.
      However, procalcitonin trend was found to be useful in early identification of
      post-traumatic septic course and its use is suggested (Recommendation Grade: B)
      in clinical practice.

PMID- 24119651
TI  - Complications related to fracture treatment in HIV patients: a case report.
AB  - We present the case report of a 40-year-old woman who was HIV-positive in Highly
      Active Anti-Retroviral Therapy (HAART) and affected by femural pertrochanteric
      fracture, which was treated by endomedullary nailing. Two years after the
      surgical operation, the woman developed an aseptic symptomatic osteolysis around
      the implant. Hardware removal was resolutive. Aseptic and septic hardware
      mobilization, hardware removal, and implant decision in HIV patients with
      pertrochanteric fractures is discussed. The authors suggest close follow-up and
      prompt hardware removal, as soon as X-rays demonstrate healing signs, in HIV
      patients with fracture fixation, if general condition allows. 

PMID- 24119652
TI  - Intramedullary nailing for treatment of pathologic femoral fractures due to
      metastases.
AB  - Pathologic fractures of the femur because of bone metastases seriously affect the
      quality of life of cancer patients. Different surgical options are indicated to
      achieve a durable and solid fixation, depending on several clinical, prognostic
      and mechanical factors. Locked intramedullary nailing is currently used to treat
      pathologic femoral fractures in patients with multiple metastases when the
      trochanteric region or shaft is mainly involved. This study evaluates
      intramedullary nailing for treatment of patients with pathologic femoral
      fractures, focussing on complications, clinical and functional outcomes and
      survival rates. The series included 80 pathologic fractures treated with a
      titanium alloy Proximal Nail (Standard or Antirotation) or Lateral Anterograde
      Femoral Nail (PFN, PFNA or LAFN, Synthes) inserted in a locked static mode.
      Acrylic cement was used to fill the bone cavity after nail insertion in eight
      patients; percutaneous cementoplasty was simultaneously performed in 11 cases of
      severe ipsilateral acetabular osteolysis. Postoperative outcomes focussed on pain
      relief, postoperative mobility and quality of life and they were analysed
      retrospectively using QOL-ACD and ECOG. Eleven patients (13.75%) suffered from
      non-fatal DVT post-surgery, with no pulmonary embolism. Six patients (7.5%)
      developed superficial wound infections and two patients (2.5%) developed
      pnaeumonia. There was no loss of reduction, breakage, screw pull out, or hardware
      or implant failure that required component substitution or revision. Lung
      histotype and the contemporary presence of cerebral and visceral metastases
      appeared to be predisposing factors in reducing survival time. All patients
      attained satisfactory pain relief, early deambulation and a marked clinical
      improvement during the first 6-10 postoperative months, with gradual worsening
      thereafter from deterioration of their general condition due to cancer
      progression. The patients' survival rate was 40% at 1 year, 25% at 2 years and
      15% at 3 years. Results confirm that multiple factors related to patients and
      primary cancer may affect survival rate after femoral fracture. Intramedullary
      nailing should be indicated for pathologic fractures at femoral diaphysis and
      metaphysis when cancer is in an advanced stage. This procedure offers good and
      durable stability, and enables pain relief, early postoperative mobilisation and
      weight-bearing, thus improving the quality of life of cancer patients. 

PMID- 24119653
TI  - The effect of temperature and a herbicide mixture on freshwater periphytic algae.
AB  - Temperature is a strong driver of biofilm formation and of the dynamics of
      microalgae in freshwater. Moreover, exposure to herbicides is a well-known
      stressor of periphytic communities in anthropized aquatic environments. We tested
      these two environmental factors on periphytic communities that had been sampled
      from the littoral zone of Lake Geneva and acclimatized in the lab for 3 weeks at
      18, 21, 24 and 28  degrees C. After this acclimation period, differences in the
      composition of the diatom community and decreases in cell density were observed
      corresponding to the temperature gradient. These acclimated communities were then
      exposed to 23 and 140 nM of a mixture composed of equitoxic quantities of
      atrazine, terbutryn, diuron and isoproturon. The periphytic community was more
      sensitive to the herbicide mixture at 18  degrees C than at higher temperatures,
      suggesting that higher temperature reduced its toxicity. Small and pioneer diatom
      species known to be promoted by contamination also appeared to benefit from
      higher temperatures. Temperature therefore appears to condition the herbicide
      sensitivity of periphytic communities.

PMID- 24119654
TI  - River otters as biomonitors for organochlorine pesticides, PCBs, and PBDEs in
      Illinois.
AB  - The North American river otter (Lontra canadensis) is a biomonitor for
      organohalogenated compounds (OHCs) associated with a wide range of deleterious
      health effects in wildlife and humans. We determined concentrations of twenty
      OHCs in livers of 23 river otters salvaged by the Illinois Department of Natural
      Resources from 2009 to 2011, determined sex-dependent distribution of OHCs, and
      compared our results to the reported concentrations of four OHCs in Illinois
      river otters from 1984 to 1989. Since these contaminants have been banned for
      over 30 years, we predicted smaller mean concentrations than those previously
      reported in Illinois otters. We detected eleven of twenty OHCs; PCBs
      (polychlorinated biphenyls), dieldrin, and 4,4'-DDE
      (dichlorodiphenyldichloroethylene) were present in the greatest mean
      concentrations. We report the largest mean concentration of dieldrin to date in
      the liver of North American river otters (mean: 174, range: 14.4-534 parts per
      billion wet wt [ppb]). Mean PCB concentrations were significantly higher in males
      (mean: 851; range: 30-3450 ppb) than females (mean: 282; range: 40-850 ppb;
      p=0.04). Mean concentrations of dieldrin were greater than those detected in
      otters from 1984 to 1989 (mean: 90; range: 30-130 ppb; p<0.05). Our results
      suggest OHC exposure remains a concern. Future research in Illinois should focus
      on evaluating OHCs exposures, particularly dieldrin, at the watershed level.

PMID- 24119655
TI  - Differentiating Swyer syndrome and complete androgen insensitivity syndrome: a
      diagnostic dilemma.
AB  - BACKGROUND: Swyer syndrome and complete androgen insensitivity syndrome are
      disorders of sex development in which patients present a female phenotype and
      46,XY karyotype. CASE: The authors present a case report of an 18-year-old
      patient with primary amenorrhea and delayed puberty. The karyotype was 46,XY. No
      mutations of sex-determining region Y gene and androgen receptor genes were
      identified, and imaging methods failed to show mullerian structures. A diagnosis
      of complete androgen insensitivity syndrome was presumed, but after hormonal
      replacement therapy was started a "hidden" uterus developed, leading to the
      definite diagnosis of Swyer syndrome. SUMMARY AND CONCLUSION: The diagnosis of
      Swyer syndrome can be challenging, because visualization of mullerian structures
      is sometimes difficult and analysis of genetic mutations is not helpful in the
      majority of cases.

PMID- 24119656
TI  - The prevalence of HPV associated cervical intraepithelial neoplasia in women
      under age 21: who will be missed under the new cervical cancer screening
      guidelines?
AB  - STUDY OBJECTIVE: To quantify the number of adolescent females < age 21 years with
      pre-cancerous cervical lesions (cervical intraepithelial neoplasia grade 2 or
      higher (CIN 2+) or adenocarcinoma in situ (AIS)) in Connecticut in the time
      period before new cervical screening recommendations went into effect and
      identify any demographic associations with a diagnosis of CIN 3. DESIGN:
      Descriptive analysis, surveillance. SETTING: CIN 2+/AIS precancerous cervical
      lesions have been reportable conditions in Connecticut since 2008 for the purpose
      of public health surveillance. PARTICIPANTS: All women < 21 years old with pre
      cancerous cervical lesions diagnosed between 2008 and 2010 (N = 681). RESULTS: Of
      the 681 reports, 478 (70.2%) women had CIN 2, 92 had CIN 2/3 (13.5%), and 110
      (16.2%) had CIN 3. CIN 3 occurred at an average rate statewide of 19/100,000 per
      year for women ages 13-20. The majority of adolescents with pre-cancerous
      cervical lesions CIN 2+/AIS (70%) were 19 and 20 years of age. CIN 3 vs CIN 2 is
      not found to be associated with age, insurance status, specimen collection year,
      or living in a non-urban vs urban county. CONCLUSION: The majority of cases of
      pre-cancerous cervical lesions in adolescents diagnosed before new screening
      recommendations were in effect are CIN 2 and therefore, likely to regress. CIN 3
      has been infrequently found in adolescent females under age 19 years; however,
      under the new screening guidelines, 110 cases of CIN 3 including 77 in women 19
      20 years could have been missed in the adolescent female in Connecticut from 2008
      2010 (54.4 per 100,000 per year for 19-20 year olds). Based upon these findings,
      it is necessary that clinicians educate adolescents and parents about the new
      screening guidelines and the importance of establishing regular cervical cancer
      screening beginning at age 21.

PMID- 24119657
TI  - Angioleiomyoma uterus in an adolescent girl: a highly unusual presentation.
AB  - BACKGROUND: Uterine angioleiomyoma is a very rare gynecologic tumor; only a few
      such cases have been reported to date and we have found no such tumor reported in
      an adolescent girl. CASE: We report the case of a uterine angioleiomyoma in an
      adolescent girl. It presented as a huge abdomino-pelvic mass. The girl had severe
      menorrhagia and severe anemia. Intra-operatively no distinct planes were found
      between myoma and myometrium. Due to severe hemorrhage, she underwent sub-total
      abdominal hysterectomy. SUMMARY AND CONCLUSION: Uterine angioleiomyoma is an
      extremely rare tumor since only 16 such cases have been reported to date. Its
      appearance in an adolescent girl seems to be the first case of its kind. So it is
      being reported not only to familiarize the managing physicians with the
      possibility of such a tumor and its variable presentation, but also to highlight
      the need for inclusion of this tumor in WHO classification of tumors of the
      female genital tract.

PMID- 24119658
TI  - Testing and treatment for sexually transmitted infections in adolescents--what's
      new?
AB  - BACKGROUND: Significant changes are taking place in the diagnosis and management
      of sexually transmitted infections (STI) in adolescents and young adults.
      FINDINGS: In this review article, we provide an update of STIs in adolescents and
      young adults including: (1) Adolescent risk; (2) Screening guidelines; (3)
      Clinical manifestations; (4) Diagnostic testing; (5) Treatment; and (6)
      Prevention; with an emphasis on "what's new" in the field.
      CONCLUSIONS/SIGNIFICANCE: While the impacts of STI epidemiology and health care
      access are leading to new recommendations for screening and prevention, changes
      in technology and drug resistance are promoting new methods of STI testing and
      ongoing revisions of STI treatment recommendations.

PMID- 24119659
TI  - Equity in maternal, newborn, and child health care coverage in India.
AB  - BACKGROUND: Addressing inequitable coverage of maternal and child health care
      services among different socioeconomic strata of population and across states is
      an important part of India's contemporary health program. This has wide
      implications for the achievement of the Millennium Development Goal targets.
      OBJECTIVE: This paper assesses the inequity in coverage of maternal, newborn, and
      child health (MNCH) care services across household wealth quintiles in India and
      its states. DESIGN: Utilizing the District Level Household and Facility Survey
      conducted during 2007-08, this paper has constructed a Composite Coverage Index
      (CCI) in MNCH care. RESULTS: The mean overall coverage of 45% was estimated at
      the national level, ranging from 31% for the poorest to 60% for the wealthiest
      quintile. Moreover, a massive state-wise difference across wealth quintiles was
      observed in the mean overall CCI. Almost half of the Indian states and union
      territories recorded a <=50% coverage in MNCH care services, which demands
      special attention. CONCLUSION: India needs focused efforts to address the
      inequity in coverage of health care services by recognising or defining
      underserved people and pursuing well-planned time-oriented health programs
      committed to ameliorate the present state of MNCH care.

PMID- 24119660
TI  - The mismatch between the health research and development (R&D) that is needed and
      the R&D that is undertaken: an overview of the problem, the causes, and
      solutions.
AB  - One of the most pressing global health problems is that there is a mismatch
      between the health research and development (R&D) that is needed and that which
      is undertaken. The dependence of health R&D on market incentives in the for
      profit private sector and the lack of coordination by public and philanthropic
      funders on global R&D priorities have resulted in a global health R&D landscape
      that neglects certain products and populations and is characterised, more
      generally, by a distribution that is not 'needs-driven'. This article provides an
      overview of the mismatch, its causes, and solutions. 

PMID- 24119661
TI  - The implications of unconventional drilling for natural gas: a global public
      health concern.
AB  - Unconventional drilling for natural gas by means of high volume horizontal
      hydraulic fracturing (fracking) is an important global public health issue. Given
      that no sound epidemiologic study has been done to assess the extent of exposure
      related adverse health effects among populations living in areas where natural
      gas extraction is going on, it is imperative that research be conducted to
      quantify the potential risks to the environment and to human health not just in
      the short-term, but over a longer time period since many diseases (i.e., cancers)
      appear years after exposure. It should not be concluded that an absence of data
      implies that no harm is being done. 

PMID- 24119662
TI  - Tethering the assembly of SNARE complexes.
AB  - The fusion of transport vesicles with their target membranes is fundamental for
      intracellular membrane trafficking and diverse physiological processes and is
      driven by the assembly of functional soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) complexes. Prior to fusion, transport
      vesicles are physically linked to their target membranes by various tethering
      factors. Recent studies suggest that tethering factors also positively regulate
      the assembly of functional SNARE complexes, thereby coupling tethering with
      fusion events. This coupling is mediated, at least in part, by direct physical
      interactions between tethering factors, SNAREs, and Sec1/Munc18 (SM) proteins. In
      this review we summarize recent progress in understanding the roles of tethering
      factors in the assembly of specific and functional SNARE complexes driving
      membrane-fusion events. 

PMID- 24119663
TI  - HIV trafficking in host cells: motors wanted!
AB  - Throughout the viral replication cycle, viral proteins, complexes, and particles
      need to be transported within host cells. These transport events are dependent on
      the host cell cytoskeleton and molecular motors. However, the mechanisms by which
      virus is trafficked along cytoskeleton filaments and how molecular motors are
      recruited and regulated to guarantee successful integration of the viral genome
      and production of new viruses has only recently begun to be understood. Recent
      studies on HIV have identified specific molecular motors involved in the
      trafficking of these viral particles. Here we review recent literature on the
      transport of HIV components in the cell, provide evidence for the identity and
      role of molecular motors in this process, and highlight how these trafficking
      events may be related to those occurring with other viruses. 

PMID- 24119665
TI  - Getting rid of DNA methylation.
AB  - Methylation of cytosine within DNA is associated with transcriptional repression
      and genome surveillance. In plants and animals, conserved pathways exist to
      establish and maintain this epigenetic mark. Mechanisms underlining its removal
      are, however, diverse and controversial and can depend on DNA synthesis (passive)
      or be independent of it (active). Ten-eleven translocation (Tet)-mediated
      conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has
      recently been evoked as a possible mechanism in the initiation of active and
      passive DNA demethylation. This review discuses the recent progress in this
      exciting area. 

PMID- 24119664
TI  - Immune synapse: conductor of orchestrated organelle movement.
AB  - To ensure proper cell function, intracellular organelles are not randomly
      distributed within the cell, but polarized and highly constrained by the
      cytoskeleton and associated adaptor proteins. This relationship between
      distribution and function was originally found in neurons and epithelial cells;
      however, recent evidence suggests that it is a general phenomenon occurring in
      many highly specialized cells including T lymphocytes. Recent studies reveal that
      the orchestrated redistribution of organelles is dependent on antigen-specific
      activation of and immune synapse (IS) formation by T cells. This review
      highlights the functional implications of organelle polarization in early T cell
      activation and examines recent findings on how the IS sets the rhythm of
      organelle motion and the spread of the activation signal to the nucleus. 

PMID- 24119666
TI  - Onychomadesis and pyogenic granulomas after postoperative upper-limb
      immobilization.

PMID- 24119667
TI  - Type 2 mosaicism in familial glomangiomatosis.

PMID- 24119669
TI  - A biosynthetic enzyme worms its way out of a conserved mechanism.

PMID- 24119668
TI  - How stable are diurnal cortisol activity indices in healthy individuals? Evidence
      from three multi-wave studies.
AB  - BACKGROUND: Indices of cortisol activity, including the cortisol awakening
      response (CAR), diurnal slope, and cortisol output across the day (total daily
      output), are often studied as mechanistic indicators that could link stress with
      health. Yet there is a paucity of data speaking to their temporal features,
      particularly whether they behave in a more state- or trait-like manner across
      time. METHODS: To address this issue, data from 3 studies were used to assess
      CAR, diurnal slope and total daily output stability over different age groups and
      time spans: 130 healthy children and adolescents collected salivary cortisol
      samples 5 times/day (1, 4, 9 and 11h after wake) over 2 days at 5 visits spaced 6
      months apart (Study 1); 147 adolescent girls collected saliva 6 times/day (wake,
      1, 4, 9 and 14 h after wake) for 2 days at 3 visits, each a year apart (Study 2);
      and 47 healthy, primarily middle age adults collected saliva 6 times/day (wake,
      1, 4, 9 and 14 h after wake) for 3 days at 4 visits spaced 2-3 months apart
      (Study 3). Stability was estimated by multilevel model-derived intraclass
      correlation coefficients (ICCs). RESULTS: Across studies, approximately 50% of
      the variance in cortisol indices was attributable to day-to-day fluctuations,
      suggesting state-like properties. Of the indices, total daily output emerged as
      the most stable over time, followed by diurnal slope and CAR, but stability
      estimates were generally quite modest regardless of index and sample. Over time
      spans of >1 year, ICCs were <= .13. CONCLUSIONS: Most of the variance in CAR,
      diurnal slope and total daily output reflects day-to-day fluctuation; there was
      little evidence for more stable trait-like influences. These findings suggest
      that future research should focus on short-term fluctuations in stress, cortisol
      and health, as opposed to lengthy disease processes.

PMID- 24119670
TI  - The architecture of restriction enzymes.

PMID- 24119671
TI  - Amyloid structures from Alzheimer's disease patients.

PMID- 24119672
TI  - Ad hominem.

PMID- 24119673
TI  - Venoarterial extracorporeal membrane oxygenation (VA ECMO) to facilitate combined
      pneumonectomy and tracheoesophageal fistula repair.

PMID- 24119674
TI  - Case 2--2014: Aortic dissection: real or artifact?

PMID- 24119675
TI  - Usage of EZ-blocker on bilateral videothoracoscopic sympathectomy.

PMID- 24119676
TI  - The role of nonocclusive sources of acute gut injury in cardiac surgery.

PMID- 24119677
TI  - Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional
      outcomes.
AB  - OBJECTIVE: To present our experience with laparoscopic partial nephrectomy (LPN)
      for hilar tumors and evaluate intermediate oncologic and renal functional
      outcomes. MATERIALS AND METHODS: A retrospective review of LPN cases performed in
      488 patients was performed. Hilar lesions were defined as renal cortical tumors
      in direct physical contact with the renal artery, vein, or both, as identified on
      preoperative imaging and confirmed intraoperatively. The clinicopathologic
      parameters, perioperative course, complications, and oncologic and 6-month renal
      functional outcomes were analyzed. RESULTS: A total of 488 patients underwent
      LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors
      was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for
      hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean
      estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL).
      There were no statistically significant differences noted in any of the
      perioperative parameters investigated despite a higher nephrometry complexity
      score in the hilar group. Change in estimated glomerular filtration rate at 6
      months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar
      tumors, respectively (P = NS). There was 1 recurrence detected in the hilar
      group, with a median follow-up of 41.6 months. CONCLUSION: In the hands of an
      experienced laparoscopist, LPN can safely be performed for hilar tumors, with
      preservation of perioperative outcomes and durable renal functional and oncologic
      outcomes.

PMID- 24119678
TI  - An evaluation of thyrotoxic autoimmune thyroiditis patients with triplex Doppler
      ultrasonography.
AB  - OBJECTIVE: This study aimed to investigate the usefulness of blood flow
      parameters obtained from STA and CCA with Triplex Doppler ultrasonography (TDU)
      on patients with thyrotoxicosis. MATERIALS AND METHODS: This cross-sectional
      study included consecutive 24 patients with thyrotoxicosis and 18 healthy
      controls. The thyroid gland blood flow parameters were evaluated with TDU.
      RESULTS: The thyroid volumes and FT3, TRAb, 4-h and 24-h radioactive iodine
      uptake (RAIU) levels of Group 1 were significantly high compared to those of
      Group 2. The thyroid volumes and FT3, FT4 and TSH levels of both Group 1 and
      Group 2 showed a statistically significant difference compared to Group 3. STA
      PSV values for Group 1, Group 2 and Group 3 were 138 cm/s, 54 cm/s and 37 cm/s,
      respectively. STA-EDV values for these groups were 60 cm/s, 25 cm/s and 15 cm/s,
      respectively. PSVR values for these groups were 1.01, 0.45, 0.34 cm/s,
      respectively. EDVR values for these groups were 1.29, 0.70 and 0.49 cm/s,
      respectively. In Group 1, STA-PSV, STA-EDV, PSVR and EDVR values were
      significantly high compared to those of Group 2. RAIU levels showed a significant
      positive correlation with the STA-PSV, STA-EDV and PSVR. CONCLUSION: The thyroid
      gland blood flow parameters may be used in clinical diagnosis of patients with
      thyrotoxicosis.

PMID- 24119679
TI  - Finite element modeling of embolic coil deployment: multifactor characterization
      of treatment effects on cerebral aneurysm hemodynamics.
AB  - Endovascular coiling is the most common treatment for cerebral aneurysms. During
      the treatment, a sequence of embolic coils with different stiffness, shapes,
      sizes, and lengths is deployed to fill the aneurysmal sac. Although coil packing
      density has been clinically correlated with treatment success, many studies have
      also reported success at low packing densities, as well as recurrence at high
      packing densities. Such reports indicate that other factors may influence
      treatment success. In this study, we used a novel finite element approach and
      computational fluid dynamics (CFD) to investigate the effects of packing density,
      coil shape, aneurysmal neck size, and parent vessel flow rate on aneurysmal
      hemodynamics. The study examines a testbed of 80 unique CFD simulations of post
      treatment flows in idealized basilar tip aneurysm models. Simulated coil
      deployments were validated against in vitro and in vivo deployments. Among the
      investigated factors, packing density had the largest effect on intra-aneurysmal
      velocities. However, multifactor analysis of variance showed that coil shape can
      also have considerable effects, depending on packing density and neck size.
      Further, linear regression analysis showed an inverse relationship between mean
      void diameter in the aneurysm and mean intra-aneurysmal velocities, which
      underscores the importance of coil distribution and thus coil shape. Our study
      suggests that while packing density plays a key role in determining post
      treatment hemodynamics, other factors such as coil shape, aneurysmal geometry,
      and parent vessel flow may also be very important. 

PMID- 24119680
TI  - New clinical practice guidelines of the surviving sepsis campaign: a critical
      appraisal.
AB  - In 2004 was published the first edition of the "Surviving sepsis campaign"
      guidelines for the management of severe sepsis and septic shock, opening a new
      era in the treatment of this syndrome. The paradox is that guidelines application
      have produced positive results despite including in some cases treatments proven
      ineffective. Eight years later has been published the third edition of the
      guides, which updates the prior in the light of new knowledge, but the quality of
      evidence remains weak. In this paper the authors express their critical view on
      the current edition of the guides, pointing out their weaknesses and suggesting
      how the development of future editions should be. 

PMID- 24119681
TI  - A review of the effects of pregabalin on sleep disturbance across multiple
      clinical conditions.
AB  - Pregabalin is approved for the treatment of a variety of clinical conditions and
      its analgesic, anxiolytic and anticonvulsant properties are well documented.
      Pregabalin's effects on sleep, however, are less well known. This review
      summarizes the published data on the effects of pregabalin on sleep disturbance
      associated with neuropathic pain, fibromyalgia, restless legs syndrome, partial
      onset seizures and general anxiety disorder. The data demonstrate that pregabalin
      has a positive benefit on sleep disturbance associated with several different
      clinical conditions. Polysomnographic data reveal that pregabalin primarily
      affects sleep maintenance. The evidence indicates that pregabalin has a direct
      effect on sleep that is distinct from its analgesic, anxiolytic and
      anticonvulsant effects. 

PMID- 24119682
TI  - Physical activity patterns among South-Asian adults: a systematic review.
AB  - Physical activity (PA) has many beneficial physical and mental health effects.
      Physical inactivity is considered the fourth leading risk factor for global
      mortality. At present there are no systematic reviews on PA patterns among South
      Asian adults residing in the region. The present study aims to systematically
      evaluate studies on PA patterns in South Asian countries. A five-staged
      comprehensive search of the literature was conducted in Medline, Web of Science
      and SciVerse Scopus using keywords 'Exercise', 'Walking', 'Physical activity',
      'Inactivity', 'Physical Activity Questionnaire', 'International Physical Activity
      Questionnaire', 'IPAQ', 'Global Physical Activity Questionnaire' and 'GPAQ',
      combined with individual country names. The search was restricted to English
      language articles conducted in humans and published before 31st December 2012. To
      obtain additional data a manual search of the reference lists of articles was
      performed. Data were also retrieved from the search of relevant web sites and
      online resources. The total number of hits obtained from the initial search was
      1,771. The total number of research articles included in the present review is
      eleven (India-8, Sri Lanka-2, Pakistan-1). In addition, eleven country reports
      (Nepal-3, Bangladesh-2, India-2, Sri Lanka-2, Bhutan-1, Maldives-1) of World
      Health Organization STEPS survey from the South-Asian countries were retrieved
      online. In the research articles the overall prevalence of inactivity was as
      follows; India (18.5%-88.4%), Pakistan (60.1%) and Sri Lanka (11.0%-31.8%). STEPS
      survey reports were available from all countries except Pakistan. Overall in
      majority of STEPS surveys females were more inactive compared to males.
      Furthermore, leisure related inactivity was >75% in studies reporting inactivity
      in this domain and people were more active in transport domain when compared with
      the other domains. In conclusion, our results show that there is a wide variation
      in the prevalence of physical inactivity among South-Asian adults within and
      between countries. Furthermore, physical inactivity in South Asian adults was
      associated with several socio-demographic characteristics. Majority of South
      Asian adults were inactive during their leisure time. These Factors need to be
      considered when planning future interventions and research aimed at improving PA
      in the region. 

PMID- 24119683
TI  - [Prevention of serogroup B meningococcal disease using a four-component vaccine].
AB  - INTRODUCTION: Meningococcal disease is an infection caused by Neisseria
      meningitidis, and those of serogroup B are currently the most predominant. It has
      been difficult to create effective vaccines for this serogroup in order to modify
      or reduce its morbidity. The aim of this study was to review existing data on the
      new vaccine 4CMenB and its potential contribution to the prevention of this
      infection. METHODS: A panel of 12 experts (from Pediatrics, Public Health and
      Vaccinology) conducted a literature search and prioritized 74 publications. A
      review of the vaccine was then prepared, which was discussed in a meeting and
      subsequently validated by e-mail. RESULTS: 4CMenB vaccine, based on four
      components (NadA, fHbp, NHBA and OMVnz), was designed by reverse vaccinology. The
      Meningococcal Antigen Typing System (MATS) shows a potential of 70-80% coverage
      of the strains in Europe. Clinical trials show that the vaccine is safe and
      immunogenic in infants, children, adolescents, and adults, and induces an
      anamnestic response. The incidence of fever is similar to systemic vaccines
      administered alone, but higher when co-administered with them, although the fever
      pattern is predictable and self-limited. It is compatible with the Spanish
      routine vaccines, and can be administered simultaneously with the currently
      available hexavalent and pentavalent vaccines, as well as the pneumococcal
      conjugate vaccine. CONCLUSIONS: The 4CMenB vaccine is the only strategy currently
      available to prevent meningococcal disease caused by serogroup B.

PMID- 24119684
TI  - Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin
      4.
AB  - We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two
      children with mitochondrial disease (the more severe case also presented with
      macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that
      localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish
      recapitulated the mitochondrial respiratory defect observed in both individuals
      and the macrocytic anemia with megaloblastic features of the more severe case. In
      vitro and in vivo complementation studies with fibroblasts from the affected
      individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial
      respiratory homeostasis and erythropoiesis. Our findings establish mutations in
      SFXN4 as a cause of mitochondriopathy and macrocytic anemia. 

PMID- 24119685
TI  - ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic
      lateral sclerosis type 19.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder
      characterized by the degeneration of motor neurons and typically results in death
      within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases,
      and the identification of genes associated with FALS is indispensable to
      elucidating the molecular pathogenesis. We identified a Japanese family affected
      by late-onset, autosomal-dominant ALS in which mutations in genes known to be
      associated with FALS were excluded. A whole- genome sequencing and parametric
      linkage analysis under the assumption of an autosomal-dominant mode of
      inheritance with incomplete penetrance revealed the mutation c.2780G>A (p.
      Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation
      in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p.
      Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve
      amino acids highly conserved among species, are predicted as probably damaging,
      and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal
      domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a
      receptor tyrosine kinase. Functional analysis revealed that these mutations led
      to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation.
      Clinical presentations of the individuals with mutations were characterized by
      the involvement of both upper and lower motor neurons, a lack of obvious
      cognitive dysfunction, and relatively slow progression. This study indicates that
      disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS
      and potentially paves the way for the development of innovative therapeutic
      strategies such using NRGs or their agonists to upregulate ErbB4 functions. 

PMID- 24119687
TI  - Respiratory health in Latin America: number of specialists and human resources
      training.
AB  - Latin America is made up of a number of developing countries. Demographic changes
      are occurring in the close to 600 million inhabitants, in whom a significant
      growth in population is combined with the progressive ageing of the population.
      This part of the world poses great challenges for general and respiratory health.
      Most of the countries have significant, or even greater, rates of chronic
      respiratory diseases or exposure to risk. Human resources in healthcare are not
      readily available, particularly in the area of respiratory disease specialists.
      Academic training centers are few and even non-existent in the majority of the
      countries. The detailed analysis of these conditions provides a basis for
      reflection on the main challenges and proposals for the management and training
      of better human resources in this specialist area.

PMID- 24119688
TI  - Endobronchial lipoma: an unusual cause of bronchial obstruction.

PMID- 24119686
TI  - Routine versus selective cardiac magnetic resonance in non-ischemic heart failure
      - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart
      failure) project 1-B).
AB  - BACKGROUND: Imaging has become a routine part of heart failure (HF)
      investigation. Echocardiography is a first-line test in HF given its availability
      and it provides valuable diagnostic and prognostic information. Cardiac magnetic
      resonance (CMR) is an emerging clinical tool in the management of patients with
      non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role
      in the detection of a variety of cardiomyopathies but there is a paucity of high
      quality evidence to support these recommendations.The primary objective of this
      study is to compare the diagnostic yield of routine cardiac magnetic resonance
      versus standard care (that is, echocardiography with only selective use of CMR)
      in patients with non-ischemic heart failure. The primary hypothesisis that the
      routine use of CMR will lead to a more specific diagnostic characterization of
      the underlying etiology of non-ischemic heart failure. This will lead to a
      reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and
      HF with preserved ejection fraction. DESIGN: Tertiary care sites in Canada and
      Finland, with dedicated HF and CMR programs, will randomize consecutive patients
      with new or deteriorating HF to routine CMR or selective CMR. All patients will
      undergo a standard clinical echocardiogram and the interpreter will assign the
      most likely HF etiology. Those undergoing CMR will also have a standard
      examination and will be assigned a HF etiology based upon the findings. The
      treating physician's impression about non-ischemic HF etiology will be collected
      following all baseline testing (including echo +/- CMR). Patients will be
      followed annually for 4 years to ascertain clinical outcomes, quality of life and
      cost. The expected outcome is that the routine CMR arm will have a significantly
      higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other'
      cardiomyopathy than the selective CMR group. DISCUSSION: This study will be the
      first multicenter randomized, controlled trial evaluating the role of CMR in non
      ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order
      to determine whether there are any gains over management strategies employing
      selective CMR utilization. The insight gained from this study should improve
      appropriate CMR use in HF. TRIAL REGISTRATION: NCT01281384.

PMID- 24119689
TI  - Chemotherapy-induced secondary pneumothorax.

PMID- 24119690
TI  - Follicle-stimulating hormone-secreting pituitary adenoma manifesting as recurrent
      ovarian cysts in a young woman--latent risk of unidentified ovarian
      hyperstimulation: a case report.
AB  - BACKGROUND: Ovarian hyperstimulation caused by follicle-stimulating hormone
      secreting gonadotroph cell adenoma is a rare, with a few reported cases, but
      almost certainly unnoticed cases occur because of the absence of detailed
      examinations. We retrospectively reviewed 200 patients treated for gonadotroph
      cell adenoma in our institute and identified 26 women of reproductive age. Two of
      these 26 patients had a history of ovarian cysts. One patient was considered to
      have had typical ovarian hyperstimulation, successfully treated by
      transsphenoidal surgery. The other patient initially underwent transsphenoidal
      surgery because of visual disturbance, but endocrinological examinations
      suggested possible relationships with previous ovarian hyperstimulation. We
      present the former case and discuss the latent risk of failure to identify this
      entity. CASE PRESENTATION: A 36-year-old woman with a sellar tumor was referred
      to our hospital with suspected ovarian hyperstimulation. She had a history of
      repeated surgery for ovarian cysts. Serum follicle-stimulating hormone and
      estradiol levels were within the normal ranges, and only the luteinizing hormone
      level was suppressed significantly. Transsphenoidal surgery achieved gross total
      tumor removal, and the histological diagnosis was follicle-stimulating hormone
      secreting gonadotroph cell adenoma. The serum follicle-stimulating hormone,
      luteinizing hormone, and estradiol levels returned to the normal ranges
      postoperatively, and the ovarian cysts subsequently decreased in size without
      particular interventions. CONCLUSION: Ovarian hyperstimulation could regress
      after resolving the causes of high follicle-stimulating hormone level, so
      avoiding unnecessary ovary surgery. Detailed endocrinological examination
      including estradiol evaluation with pituitary imaging is quite important in women
      of reproductive age to establish the correct diagnosis.

PMID- 24119691
TI  - Comparison of methods for detoxification of spruce hydrolysate for bacterial
      cellulose production.
AB  - BACKGROUND: Bacterial cellulose (BC) is a nanostructured material with unique
      properties and wide applicability. In order to decrease the production cost of
      bacterial cellulose, lignocellulose-based media have considerable potential as
      alternative cost-effective feedstocks. However, pretreatment and enzymatic
      hydrolysis of lignocellulose to sugars also generate fermentation inhibitors.
      Detoxification of lignocellulosic hydrolysates is needed to achieve efficient
      production of BC. In this investigation, different methods for detoxification of
      spruce hydrolysate prior to production of BC were compared with respect to
      effects on potential inhibitors and fermentable sugars, sugar consumption, BC
      yield, and cell viability. The objectives were to identify efficient
      detoxification methods and to achieve a better understanding of the role played
      by different inhibitors in lignocellulosic hydrolysates. RESULTS: In a first
      series of experiments, the detoxification methods investigated included
      treatments with activated charcoal, alkali [sodium hydroxide, calcium hydroxide
      (overliming), and ammonium hydroxide], anion and cation ion-exchange resins, and
      reducing agents (sodium sulfite and sodium dithionite). A second series of
      detoxification experiments included enzymatic treatments (laccase and
      peroxidase). The potential inhibitors studied included aliphatic acids, furan
      aldehydes, and phenolic compounds. The best effects in the first series of
      detoxification experiments were achieved with activated charcoal and anion
      exchanger. After detoxification with activated charcoal the BC yield was 8.2 g/L,
      while it was 7.5 g/L in a reference medium without inhibitors. Treatments with
      anion exchanger at pH 10 and pH 5.5 gave a BC yield of 7.9 g/L and 6.3 g/L,
      respectively. The first series of experiments suggested that there was a
      relationship between the BC yield and phenolic inhibitors. Therefore, the second
      series of detoxification experiments focused on treatments with phenol-oxidizing
      enzymes. The BC yield in the laccase-detoxified hydrolysate reached 5.0-5.5 g/L
      after 14 days cultivation, which demonstrated the important inhibitory role
      played by phenolic compounds. CONCLUSIONS: The investigation shows that
      detoxification methods that efficiently remove phenolics benefit bacterial growth
      and BC production. Negative effects of salts could not be excluded and the
      osmotolerance of Gluconacetobacter xylinus needs to be further investigated in
      the future. Combinations of detoxification methods that efficiently decrease the
      concentration of inhibitors remain as an interesting option.

PMID- 24119692
TI  - Autochthonous cutaneous myiasis due to Chrysomya bezziana.

PMID- 24119693
TI  - [Comparison of the effect of fluid resuscitation as guided either by lactate
      clearance rate or by central venous oxygen saturation in patients with sepsis].
AB  - OBJECTIVE: To compare the efficacy of fluid resuscitation as guided by lactate
      clearance rate (LCR) and central venous oxygen saturation (ScvO2) in patients
      with sepsis. METHODS: A prospective randomized control study was conducted. Fifty
      patients diagnosed with severe sepsis or septic shock from January 2011 to
      February 2012 in department of critical care medicine of Fourth Hospital of Hebei
      Medical University were enrolled in the study. The patients were randomly divided
      into two groups according to the sequence (each n=25): ScvO2 group and LCR group.
      After ICU admission, the patients were treated symptomatically timely, and fluid
      resuscitation was started as early as possible according to Surviving Sepsis
      Campaign guidance for management of severe sepsis and septic shock 2008. Central
      venous pressure (CVP)>=8 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure
      (MAP)>=65 mm Hg and ScvO2>=0.70 served as goal values to accomplish the fluid
      resuscitation therapy in ScvO2 group, while CVP>=8 mm Hg, MAP>=65 mm Hg, LCR>=10%
      served as goal value to accomplish the fluid resuscitation therapy in LCR group.
      The general condition and clinical characteristics on arrival in ICU, changes in
      CVP, MAP, ScvO2, lactate level and/or LCR before (0 hour) and 3, 6, 72 hours
      after the start of fluid resuscitation and the other related conditions during
      the therapy were recorded. RESULTS: There was no significant difference in
      general data or clinical characteristics before the start of therapy, occurrence
      of organ dysfunction, or treatment measures during different time periods after
      start of fluid resuscitation. Compared with the condition immediately before
      fluid resuscitation, at 3 hours after start of fluid resuscitation, CVP were
      improved in LCR and ScvO2 groups (8.58+/-1.17 mm Hg vs. 6.33+/-1.21 mm Hg, 9.08+/
      2.43 mm Hg vs. 5.33+/-0.98 mm Hg, both P<0.05); at 6 hours after start of fluid
      resuscitation, heart rate (HR) and respiratory rate (RR) were lowered in LCR and
      ScvO2 groups (HR: 96+/-18 bpm vs. 127+/-13 bpm, 98+/-13 bpm vs. 116+/-19 bpm, RR:
      23+/-3 times/min vs. 33+/-9 times/min, 24+/-5 times/min vs. 35+/-6 times/min, all
      P<0.05), oxygenation index (PaO2/FiO2) was increased in LCR and ScvO2 groups
      (179+/-41 mm Hg vs. 86+/-21 mm Hg, 202+/-33 mm Hg vs. 95+/-17 mm Hg, both
      P<0.05), and there was no significant difference in MAP in both groups. There was
      no significant difference in all indexes between two groups. In LCR group, 3
      hours after start of fluid resuscitation, lactate level was significantly
      decreased (2.81+/-0.18 mmol/L vs. 3.43+/-1.31 mmol/L, P<0.05). Compared with the
      value 3 hours after start of fluid resuscitation, LCR was significantly improved
      at 6 hours and 72 hours after start of fluid resuscitation in LCR group [(42.69+/
      8.75)%, (48.87+/-9.69)% vs. (20.32+/-4.58)%, both P<0.05]. Compared with that
      immediately before fluid resuscitation, ScvO2 was significant improved in ScvO2
      group at 3 hours after start of fluid resuscitation (0.65+/-0.04 vs. 0.53+/-0.06,
      P<0.05). There was no significant difference in success rate of fluid
      resuscitation comparing that of 6 hours and that of 72 hours [6 hours: 72%
      (18/25) vs. 64% (16/25), chi(2)=0.368, P=0.762; 72 hours: 88% (22/25) vs. 88%
      (22/25) ,chi(2)=0.000, P=1.000], length of ICU stay (8+/-3 days vs. 10+/-4 days,
      t=0.533, P=0.874), length of hospital stay (29+/-11 days vs. 35+/-16 days,
      t=0.692, P=0.531), improvement rate [84% (21/25) vs. 76%(19/25), chi(2)=0.500,
      P=0.480] or 28-day mortality [20% (5/25) vs. 28% (7/25), chi(2)=0.439, P=0.742]
      between LCR and ScvO2 groups. CONCLUSIONS: Both LCR and ScvO2 can be taken as the
      index in confirming the endpoint of fluid resuscitation for patients with severe
      sepsis and septic shock. Fluid resuscitation therapy under the guidance of LCR is
      accurate and reliable in patients with severe sepsis and septic shock.

PMID- 24119694
TI  - [The study of pro-B-type natriuretic peptide in the evaluation of the cardiac
      function in patients with severe sepsis].
AB  - OBJECTIVE: To evaluate plasma N-terminal pro-B-type natriuretic peptide (NT
      proBNP) levels as a marker of cardiac function during severe sepsis and septic
      shock. METHODS: A prospective study was conducted, and 44 patients without
      history of heart diseases but suffering from severe sepsis and septic shock
      underwent the transesophageal echocardiography (TEE) to obtain data about left
      and right ventricular function on 1, 3, 7 days in intensive care unit (ICU). At
      the same time, blood samples were collected to measure the levels of plasma NT
      proBNP, quality of creatine kinase isoenzyme (CK-MBmass), troponin T (cTnT) and
      lactate. The factors affecting plasma NT-proBNP levels in patients with severe
      sepsis and septic shock were analyzed, and correlation between NT-proBNP and
      cardiac function indexes were evaluated. RESULTS: Of 44 patient with severe
      sepsis and septic shock, 21 cases died in 28 days, with the mortality rate of
      47.73%. The plasma NT-proBNP values on 1, 3, 7 days in ICU of 21 non-survivors
      were obviously higher than those of 23 survivors [10 112 (855-35 000) ng/L vs. 4
      116 (185-28 437)ng/L, Z=-2.622, P=0.009; 13 811 (1 127-35 000) ng/L vs. 899 (116
      35 000)ng/L, Z=-3.459, P=0.000; 6 786 (398-35 000) ng/L vs. 623 (98-4 118)ng/L,
      Z=-3.001, P=0.003]. Non-conditional logistic regression analysis and linear
      regression analysis, plasma lactate (t=2.420, P=0.020) and acute physiology and
      chronic health evaluation system II (APACHEII) score (t=3.482, P=0.001) on day 1,
      and left ventricular ejection fraction (LVEF, t=-2.326, P=0.029) on day 7 showed
      that they were independent affecting factors for plasma NT-proBNP levels.
      Patients were subdivided into two groups based on LVEF. It was found that the
      plasma NT-proBNP values in abnormal group (LVEF<0.50, n=8) were significantly
      higher than those in normal group (LVEF>=0.50, n=17) on day 7 [1 231 (398-5 000)
      ng/L vs. 513 (98-10 047) ng/L, Z=-1.831, P=0.047]. CONCLUSIONS: Plasma NT-proBNP
      levels on day 7 in ICU could reflect the left ventricular systolic dysfunction in
      patients with severe sepsis and septic shock.

PMID- 24119695
TI  - [Assessment of the value of acute physiology and chronic health evaluation II/IV
      prognostic models in elderly patients with sepsis].
AB  - OBJECTIVE: To assess and compare the performance of acute physiology and chronic
      health evaluation II/IV (APACHEII/IV) prognostic models in elderly patients with
      sepsis. METHODS: A totally of 82 elderly patients with sepsis were
      retrospectively assessed in geriatric intensive care unit of General Hospital of
      Guangzhou Military Command between July 2011 and December 2011. APACHEII/IV
      scores were recorded within 24 hours after admission. The prognosis accuracy of
      both scores was assessed by area under the receiver operating characteristic
      curve (AUC). Based on the best cutoff value corresponding with the highest
      accuracy, patients were divided into the low and high risk of hospital mortality
      group. The predictive power of APACHEII/IV in total population and subgroups was
      compared. RESULTS: Patients with severe sepsis constituted 57.3% (47/82) of all
      patients with sepsis, and hospital mortality was 61.0% (50/82). APACHEII/IV
      scores of the patients were 17.5+/-6.3 and 55.8+/-22.3, and mortality rate was
      22.5% (18.4/82) and 17.9% (14.6/82) respectively, with significant differences
      compared with actual mortality (both P<0.01). Both APACHEII/IV scores showed
      underestimation of hospital mortality in total population [standardized mortality
      ratio (SMR) with APACHEII=2.71, 95% confidence interval (95%CI) 1.92-3.48 and SMR
      with APACHEIV=3.33, 95%CI 2.79-4.37]. APACHEII (AUC 0.664+/-0.066), and APACHEIV
      presented poor estimation(AUC 0.716+/-0.056). There was no difference in accuracy
      in prognosticating hospital death prognosis between the two APACHE models
      (Z=0.991, P=0.322). Cutoff values of APACHEII/IV were >11 and >59. According to
      the value, patients were divided into the low and high risk hospital mortality
      group. There was no significant difference between actual mortality and
      prognostic mortality in APACHEII low risk group [0-11, 20.0% (3/15) vs. 1.6%
      (0.2/15), Z=-1.023, P=0.306]. The actual mortality in high risk group with
      APACHEII (>11) was significantly higher than prognostic mortality [70.1% (47/67)
      vs. 27.2% (18.2/67), t=6.989, P=0.000]. In the high risk group, APACHEII
      underestimated mortality (SMR=2.58, 95%CI 2.22-3.51). The actual mortality of the
      low (0-59) and high (>59) risk group of APACHEIV were higher than prognostic
      mortality [lower risk group: 44.0% (22/50) vs. 7.5% (3.8/50), Z=-2.235, P=0.025;
      higher risk group: 87.5% (28/32) vs. 34.1% (10.9/32), Z=-4.712, P=0.000]. Two
      groups of patients with APACHEIV score, the mortality was underestimated (low
      risk group: SMR=5.90, 95%CI 5.19-7.07; high risk group: SMR=2.56, 95%CI 2.07
      3.24). Mortality rate of the low risk group with APACHEIV score was prone to be
      underestimated. CONCLUSIONS: The accuracy of APACHEII/IV are not ideal in
      foretelling mortality rate. Hospital mortality was underestimated with APACHEII
      in high risk patients, and it was underestimated with APACHEIV both in low and
      high risk patients, and it is even more prone to be underestimated in low risk
      group of APACHEIV. More accurate prognostic modality is in need in elderly
      patients with sepsis.

PMID- 24119696
TI  - [The impact of early hypoxemia on the prognosis of patients undergone general
      anesthesia patients in intensive care unit].
AB  - OBJECTIVE: To form the strategy of prevention of postoperative pulmonary
      complication, investigate the incidence of early hypoxemia after general
      anesthesia for surgery in intensive care unit (ICU), and assess its impact on the
      prognosis of patients. METHODS: Clinical data of patients who were directed
      transferred to ICU after general anesthesia for selective surgery during October
      2011 to June 2012 were analyzed retrospectively. According to the oxygenation
      index (PaO2/FiO2) obtained in 1 hour after ICU admission, patients were divided
      into three groups, normal blood oxygen level (n=134, PaO2/FiO2>300 mm Hg, 1 mm
      Hg=0.133 kPa), mild hypoxia (n=88, PaO2/FiO2 200-300 mm Hg) and moderate to
      severe hypoxia (n=49, PaO2/FiO2<=200 mm Hg) groups. Duration of mechanical
      ventilation, ICU stay days, postoperative hospital stay days, and duration of
      oxygen therapy were compared among three groups. RESULTS: Two hundred and seventy
      one patients were included. There were no statistical differences in gender, age,
      duration of operation, type of operation, and postoperative extubation. The
      incidence rate of hypoxemia (PaO2/FiO2<=300 mm Hg) was 50.6%. Duration of
      mechanical ventilation was significantly prolonged in moderate to severe hypoxia
      group as compared with normal blood oxygen group [20.3 (13.0, 46.1) hours vs.
      12.5 (6.0, 17.5) hours, D=40.803, P=0.005], the ratio of duration of mechanical
      ventilation longer than 24 hours was significantly higher in moderate to severe
      hypoxia group compared with normal blood oxygen and mild hypoxia groups (44.4%
      vs. 8.8%, 16.1%, chi(2)1=21.394, P2=0.000; chi(2)2=9.368, P2=0.002). The ICU stay
      was significantly longer in moderate to severe hypoxia group than normal blood
      oxygen and mild hypoxia groups [44.5 (21.5, 121.5) hours vs. 22.0 (18.0, 46.5)
      hours, 21.8 (19.0, 66.9) hours, D1=54.302, P1=0.000; D2=44.171, P2=0.005].
      Compared with normal blood oxygen group, postoperative hospital stay days and
      duration of oxygen therapy were significantly longer in moderate to severe
      hypoxia group [postoperative length of stay: 15.0 (12.0, 21.5) days vs. 9.0
      (12.0, 16.0) days, D=40.851, P=0.005; duration of oxygen therapy: 170.0 (97.5,
      307.5) hours vs. 89.0 (47.8, 192.0) hours, D=45.049, P=0.002]. CONCLUSIONS: The
      incidence of hypoxemia postoperative patients after general anesthesia is high
      when transferred to ICU. PaO2/FiO2<=200 mm Hg was closely related to prolonged
      duration of mechanical ventilation, ICU stay days, postoperative hospital stay
      days, and duration of oxygen therapy.

PMID- 24119697
TI  - [Role of microRNA-141 in the regulation of synthesis of high mobility group
      protein B1 in THP-1 cells].
AB  - OBJECTIVE: To investigate the regulatory effect of microRNA-141 (miR-141) on
      expression of high mobility group protein B1(HMGB1) in human monocytes THP-1 cell
      line. METHODS: THP-1 cells were transfected with miR-141 mimic or inhibitor (100
      nmol/L) for 48 hours with lipofectamine RNAi MAX. The levels of miR-141 and HMGB1
      mRNA in the THP-1 cells were detected by real-time fluorescence quantitation
      reverse transcription-polymerase chain reaction (RT-PCR), and HMGB1 protein was
      determined with Western blotting. RESULTS: The levels of miR-141 could be up
      regulated (35.33+/-7.24 vs. 1.21+/-0.20, t=-8.408, P=0.010) or down regulated
      (0.55+/-0.12 vs 1.09+/-0.05, t=7.473, P=0.002) after being transfected with 100
      nmol/L miR-141 mimic or inhibitor for 48 hours by lipofectamine RNAi MAX in THP
      1, and the level of HMGB1 mRNA and protein decreased (mRNA: 0.43+/-0.06 vs.
      0.97+/-0.08, t=9.760, P=0.001; protein: 0.63+/-0.12 vs. 1.00+/-0.11, t=2.991,
      P=0.040) or increased (mRNA: 2.13+/-0.11 vs. 1.16+/-0.13, t=-9.977, P=0.001;
      protein: 1.78+/-0.04 vs. 0.96+/-0.09, t=-13.778, P=0.000) simultaneously compared
      with the control group. CONCLUSIONS: miR-141 is involved in regulation of
      inflammation through HMGB1 gene and protein pathway, suggesting that miR-141
      plays an important role in regulating immune cells during the inflammatory
      response.

PMID- 24119698
TI  - [The comparison of the value of end-tidal partial pressure of carbon dioxide
      after eupnoea and prolonged expiratory method in Department of Respiratory
      Medicine].
AB  - OBJECTIVE: To compare and discuss the value of end-tidal partial pressure of
      carbon dioxide (PETCO2) using eupnoea or prolonged expiratory method, and explore
      their application value in department of respiratory medicine. METHODS: One
      hundred and fourteen patients admitted to the Department of Respiratory Medicine
      of hospital received PETCO2 monitor, using either eupnoea or prolonged expiratory
      method, and blood gas analysis was performed thereafter. Then the patients were
      divided into different groups according to different arterial partial pressure of
      carbon dioxide (PaCO2) and diseases. PETCO2 using two methods were compared and
      performed correlation analysis with PaCO2 was performed. A group of 45 healthy
      volunteers were served as the control group. RESULTS: (1) In healthy volunteers,
      PETCO2 using eupnoea or prolonged expiratory method was (39.68+/-5.07) mm Hg (1
      mm Hg=0.133 kPa), (40.68+/-3.25) mm Hg, respectively, and they showed a good
      correlation with PaCO2 [(40.44+/-2.70) mm Hg, r1=0.79, P1=0.02; r2=0.91,
      P2=0.04). (2) In 114 patients group, PETCO2 using eupnoea and prolonged
      expiratory method was (35.93+/-8.19) mm Hg, (40.69+/-10.71) mm Hg, respectively,
      and they showed a good correlation with PaCO2 [(42.90+/-12.62) mm Hg, r1=0.80,
      r2=0.86, both P<0.01). (3) Subgroup analysis according to different levels of
      PaCO2: in normal PaCO2 group (35-45 mm Hg, n=49), PETCO2 using eupnoea or
      prolonged expiratory method was (37.64+/-4.67) mm Hg, (38.25+/-5.03) mm Hg,
      respectively, and they showed a good correlation with PaCO2 [(39.30+/-3.10) mm
      Hg, r1=0.76, P1=0.61; r2=0.82, P2=0.65]; in low PaCO2 group (<35 mm Hg, n=26),
      PETCO2 by using eupnoea or prolonged expiratory method was (28.4+/-5.63) mm Hg,
      (31.3+/-5.47) mm Hg, respectively, and they showed a good correlation with PaCO2
      [(31.27+/-5.47) mm Hg, r1=0.68, r2=0.87, both P<0.01]; in high PaCO2 group (45-60
      mm Hg, n=27), PETCO2 by using eupnoea expiratory method [(37.07+/-5.04) mm Hg]
      showed a poor correlation with PaCO2 [(49.51+/-5.18) mm Hg, r=0.42, P=0.02),
      while PETCO2 using prolonged expiratory method [(46.61+/-3.75) mm Hg] showed a
      good correlation with PaCO2 [(49.51+/-5.18) mm Hg, r=0.81, P=0.01). In extremely
      high PaCO2 group (>60 mm Hg, n=12), PETCO2 using eupnoea or prolonged expiratory
      method [(51.37+/-11.25) mm Hg, (62.57+/-16.24) mm Hg] showed a good correlation
      with PaCO2 [(74.63+/-12.20) mm Hg, r1=0.80, P1=0.09; r2=0.82, P2=0.11]. (4)
      Subgroup analysis according to different diseases: in chronic obstructive
      pulmonary disease (COPD) group (n=31), large pleural effusion group (n=21), and
      interstitial pneumonia group (n=15), PETCO2 using eupnoea expiratory method
      [(44.62+/-12.70), (34.89+/-3.26), (34.82+/-4.51) mm Hg] showed a poor correlation
      with PaCO2 [(60.18+/-17.38), (38.02+/-3.66), (38.70+/-4.08) mm Hg, r1=0.87,
      P1<0.01; r2=0.23, P2=0.03; r3=0.56, P3=0.02], while PETCO2 using prolonged
      expiratory method [(55.63+/-16.27), (38.59+/-4.23), (37.81+/-4.23) mm Hg] showed
      a good correlation with PaCO2 [(60.18+/-17.38), (38.02+/-3.66), (38.70+/-4.08) mm
      Hg, r1=0.89, P1<0.01; r2=0.66, P2=0.02; r3=0.87, P3=0.01]. In pulmonary embolism
      group (n=16), the results of PETCO2 using eupnoea and prolonged expiratory method
      [(30.57+/-9.49) mm Hg, (32.90+/-8.57) mm Hg] showed a good correlation with PaCO2
      [(36.50+/-4.59) mm Hg, r1=0.75, r2=0.76, both P<0.01]. CONCLUSIONS: In Department
      of Respiratory Medicine, PETCO2 can replace PaCO2, but among the patients with
      COPD, interstitial pneumonia, large pleural effusion, the results of PETCO2
      measured with prolonged expiratory method could be closer to that of PaCO2 as
      compared with that of using eupnoea expiratory method. In cases with high levels
      of PaCO2, blood gas analysis should be executed. In pulmonary embolism patients,
      there was no difference between eupnoea and prolonged expiratory method, and the
      results were lower than that of PaCO2.

PMID- 24119699
TI  - [Significance of erythrocytes phosphatidylserine exposure on occurrence of anemia
      in sepsis].
AB  - OBJECTIVE: To investigate the role of phosphatidylserine (PS) exposure of
      erythrocytes in the development of anemia in sepsis patients. METHODS: A self
      control study was conducted. Thirty sepsis patients admitted to intensive care
      unit (ICU) were enrolled. Peripheral venous blood was collected on 1 day and 7
      days after ICU admission, and hemoglobin (Hb) concentration was examined
      routinely. A flow-cytometric assay based on Annexin V/ propidium iodide (Annexin
      V/PI) was used to measure the PS exposure of erythrocytes. The relationship
      between PS exposure and Hb concentration was analyzed. RESULTS: Hb concentrations
      in 30 sepsis patients at 7 days after ICU admission were significantly decreased
      compared with those of patients at 1 day (81.59+/-3.31 g/L vs. 121.90+/-3.34 g/L,
      t=8.570, P=0.000), but the percentage of PS exposure of erythrocytes was
      significantly higher [(17.19+/-1.35)% vs. (7.87+/-0.83)%, t=-6.557, P=0.000]. An
      inverse correlation was found between percentage of PS-positive RBCs and Hb
      concentration by Pearson analysis (r=-0.838, P=0.000). CONCLUSIONS: The
      percentage of PS exposure in erythrocytes is significantly increased in sepsis,
      and it might contribute to the development of anemia in sepsis patients during
      hospital stay. The more severe the anemia, the higher the PS in erythrocytes.

PMID- 24119700
TI  - [Effects of early mechanical ventilation on oxygenation and hemodynamics in acute
      high altitude pulmonary edema patients complicated by acute respiratory distress
      syndrome].
AB  - OBJECTIVE: To investigate the effect of early mechanical ventilation on
      oxygenation and hemodynamic of acute high altitude pulmonary edema (HAPE)
      patients complicated by acute respiratory distress syndrome (ARDS). METHODS: From
      May 2001 to December 2006, 8 HAPE patients with secondary ARDS admitted to Germud
      City People's Hospital were enrolled in the study. All the patients received
      early invasive mechanical ventilation within 24 hours of HAPE. Hemodynamics,
      cardiac output, arterial and mixed venous blood gas and oxygen dynamics
      parameters were determined before and after 96 hours of mechanical ventilation.
      RESULTS: Before treatment the right atrial pressure (RAP), mean pulmonary artery
      pressure (mPAP), pulmonary vascular resistance index (PVRI) and shunt (Qs/Qt)
      were above normal values. Oxygen delivery (DO2), oxygen extraction rate (O2ER),
      and oxygenation index (PaO2/FiO2) were lower than normal values. After treatment
      with mechanical ventilation, arterial partial pressure of oxygen (PaO2),
      PaO2/FiO2, arterial oxygen saturation (SaO2), partial pressure of oxygen of mixed
      venous blood (PVO2) and mixed venous oxygen saturation (SVO2) were increased
      significantly compared with those before treatment [PaO2: 70.3+/-2.9 mm Hg (1 mm
      Hg=0.133 kPa) vs. 49.9+/-3.5 mm Hg, t=15.292, P=0.001; PaO2/FiO2: 201.6 +/- 4.8
      mm Hg vs. 134.5+/-5.2 mm Hg, t=19.618, P=0.004; SaO2: 0.929+/-0.021 vs. 0.780+/
      0.073, t=6.226, P=0.002; PVO2: 54.8+/-2.9 mm Hg vs. 44.9+/-2.6 mm Hg, t=6.767,
      P=0.002; SVO2: 0.726+/-0.017 vs. 0.663+/-0.053, t=3.262, P=0.008]. Heart rate
      (HR), RAP, mPAP, pulmonary wedge pressure (PAWP), PVRI, right ventricular stroke
      work index (RVSWI) and Qs/Qt were decreased significantly compared with those
      before mechanical ventilation [HR: 73+/-2 bpm vs. 102+/-13 bpm, t=6.228, P=0.000;
      RAP: 6.9+/-1.0 mm Hg vs. 13.9+/-1.5 mm Hg, t=3.609, P=0.008; mPAP: 18.5+/-2.9 mm
      Hg vs. 41.6+/-3.0 mm Hg, t=4.773, P=0.000; PAWP: 6.9+/-2.2 mm Hg vs. 14.0+/-4.2
      mm Hg, t=2.747, P=0.030; PVRI: 26.3+/-1.7 kPa*s*L(-1) vs. 49.6+/-10.0 kPa*s*L(
      1), t=9.861, P=0.000; RVSWI: 11.0+/-1.9 g*cm(-1)*min*m(2) vs. 22.0+/-1.5 g*cm(
      1)*min*m(2), t=12.704, P=0.000; Qs/Qt: (26+/-18)% vs. (35+/-15)%, t=7.603,
      P=0.000], and cardiac index (CI), DO2, oxygen consumption (VO2) and O2ER were
      also increased [CI: 71.68+/-6.67 mL*s(-1)*m(-2) vs. 70.01+/-6.67 mL*s(-1)*m(-2),
      t=2.832, P=0.036; DO2 (L*min(-1)*m(-2)): 460.9+/-14.0 vs. 410.0+/-3.1, t=9.268,
      P=0.000; VO2 (L*min(-1)*m(-2)): 158.5+/-9.2 vs. 129.9+/-5.3, t=2.818, P=0.004;
      O2ER: (20+/-1)% vs. (18+/-1)%, t=7.652, P=0.000]. All of the 8 patients survived.
      CONCLUSIONS: Pulmonary circulation hemodynamic and oxygen dynamic disorders were
      found in HAPE patients with secondary ARDS. Treatment with early mechanical
      ventilation not only improved oxygenation but also reduced pulmonary hypertension
      and increased cardiac output and DO2.

PMID- 24119701
TI  - [The relationship between lactate clearance rate and delayed encephalopathy after
      acute carbon monoxide poisoning].
AB  - OBJECTIVE: To study the relationship between lactate clearance rate (LCR) and
      prognosis after acute carbon monoxide poisoning in patients with delayed
      encephalopathy (DEACMP). METHODS: Data from 354 patients with acute severe carbon
      monoxide poisoning (ASCOP) were retrospectively analyzed. The patients were
      divided into hyperlactacidemia group (arterial lactic acid > 2 mmol/L, n=263) and
      low lactic acidosis group (arterial lactate <=2 mmol/L, n=91) according to the
      blood lactic acid level at admission. Arterial blood (1 mL) was collected from
      all patients before and 6, 24, 72 hours after treatment at ambient air, and
      arterial blood lactic acid was determined, and LCR was calculated. The initial
      level of blood lactic acid and LCR at 6, 24, 72 hours were compared between two
      groups. At the same time, the patients with hyperlactacidemia were divided into
      high LCR group (LCR more than 10%, n=101) and low LCR group (LCR less than or
      equal to 10%, n=162) according to 6-hour LCR, and the incidence of DEACMP was
      compared between two groups. The relationship between LCR and the incidence of
      DEACMP was analyzed with Spearman linear correlation analysis. The risk factors
      associated with DEACMP were analyzed with logistic regression analysis. RESULTS:
      The initial level of blood lactic acid (2.73+/-0.57 mmol/L vs. 1.69+/-0.20
      mmol/L, t=5.327, P=0.001) and LCR at 6, 24, 72 hours [6 hours: (9.0+/-2.4)% vs.
      (1.2+/-0.6)%, t=9.468, P=0.001; 24 hours: (8.6+/-3.7)% vs. (1.2+/-0.4)%, t=4.889,
      P=0.001; 72 hours: (14.0+/-3.9)% vs. (1.7+/-1.0)%, t=5.211, P=0.001] in
      hyperlactacidemia group were significantly higher than those in low lactic
      acidosis group. The initial level of blood lactic acid in high LCR group was
      significantly lower than that in low LCR group (2.41+/-0.23 mmol/L vs. 2.92+/
      0.63 mmol/L, t=2.429, P=0.023), and LCR at 6 hours and 24 hours were
      significantly higher than those in low LCR group [6 hours: (11.0+/-1.2)% vs.
      (8.0+/-2.1)%, t=4.487, P=0.001; 24 hours: (12.2+/-3.0)% vs. (6.3+/-1.8)%,
      t=6.264, P=0.001]. But there was no difference in 72-hour LCR between high LCR
      group and low LCR group [(14.1+/-3.6)% vs. (13.9+/-4.1)%, t=0.182, P=0.857]. The
      incidence of DEACMP in high LCR group was significantly lower than that in low
      LCR group [15.8% (16/101) vs. 61.1% (99/162), chi(2)=51.814, P=0.001]. The blood
      LCR at early period (6, 24, 72 hours) in ASCOP patients with hyperlactacidemia
      was negatively correlated with the incidence of DEACMP (r1=-0.493, P1=0.011; r2=
      0.408, P2=0.038; r3=-0.428, P3=0.029). Logistic regression analysis showed that
      LRC at 6 hours and 24 hours [odds ratio (OR) was 2.701, 1.070, P value was 0.035,
      0.001], long-time coma (OR=1.537, P=0.068), contact carbon monoxide (CO) long
      time (OR=2.686, P=0.014), age (OR=1.464, P=0.017), acute carbon monoxide
      complications (OR=1.363, P=0.072) patients with ASCOP had an increased risk of
      DEACMP. CONCLUSIONS: LCR is helpful for the assess of DEACMP patients severity,
      for the treatment guide and for prognosis judgement.

PMID- 24119702
TI  - [Effects of probiotics on blood glucose levels and clinical outcomes in patients
      with severe craniocerebral trauma].
AB  - OBJECTIVE: To investigate the effects of probiotics on blood glucose levels and
      clinical outcomes in patients suffering from severe craniocerebral trauma.
      METHODS: A prospective randomized control study was conducted. Fifty-two severe
      craniocerebral trauma patients admitted to intensive care unit (ICU) were
      randomized into experimental or control group (each n=26). All patients received
      conventional treatment according to Guidelines for the Clinical Management of
      Traumatic Brain Injury and enteral nutrition within 24-48 hours after admission
      through nasogastric tube. In addition, the experimental group received 1*10(9)
      bacteria of viable probiotics (Golden Bifid, 3.5 g for 3 times per day) per day
      for 21 days. The fasting blood glucose levels were determined in the morning
      before intervention and on day 4, 8, 15, 21 after intervention. Amount of insulin
      used during hospitalization, Glasgow coma scale (GCS) scores, length of ICU stay,
      and 28-day mortality rate were studied. RESULTS: There was no difference in term
      of the blood glucose levels between two groups before intervention. On day 8 and
      15 after intervention, significantly lower levels of fasting blood glucose were
      observed in the experimental group compared with those of the control group (8
      days: 6.6+/-1.2 mmol/L vs. 8.0+/-2.7 mmol/L, t=-2.500, P=0.017; 15 days: 6.1+/
      1.4 mmol/L vs. 7.2+/-2.2 mmol/L, t=-2.269, P=0.028). There were significantly
      less patients treated with insulin or shorter days of insulin therapy in
      experimental group than in control group [19.2% (5/26) vs. 46.2% (12/26),
      chi(2)=4.282, P=0.039; 1.6+/-0.9 vs. 4.3+/-3.1, t=-2.698, P=0.017]. The length of
      ICU stay was significantly shorter in the experimental group than that of control
      group (6.8+/-3.8 days vs. 10.7+/-7.3 days, t=-2.123, P=0.034). No significant
      differences were found about the GCS scores (before intervention: 6.3+/-1.0 vs.
      6.4+/-1.0, t=-0.408, P=0.685; 21 days after intervention: 10.1+/-4.0 vs. 9.6+/
      4.3, t=0.435, P=0.665) and 28-day mortality rate [11.5% (3/26) vs. 19.2% (5/26),
      chi(2)=0.148, P=0.701] between experimental group and control group. CONCLUSIONS:
      Probiotics could facilitate blood glucose control in patients with severe
      craniocerebral injury. The underlying mechanisms and its long-term efficacy in
      this category of patients, however, need to be further investigated.

PMID- 24119703
TI  - [Occurrence of septic shock, herpes and coagulopathy due to Aeromonas hydrophila
      infection: a report of one case].

PMID- 24119704
TI  - [Advance in protective mechanical ventilation with low tidal volume].

PMID- 24119705
TI  - [Successful treatment of pan-resistant Acinetobacter baumannii infection of the
      lung with tigecycline: a report of one case].

PMID- 24119706
TI  - [Effect of extracorporeal membrane oxygenation on pharmacokinetics of common
      drugs].

PMID- 24119707
TI  - Nebulised amphotericin B to eradicate Candida colonisation from the respiratory
      tract in critically ill patients receiving selective digestive decontamination: a
      cohort study.
AB  - INTRODUCTION: Colonisation of the lower respiratory tract with Candida species
      occurs in 25% of mechanically ventilated critically ill patients, and is
      associated with increased morbidity. Nebulised amphotericin B has been used to
      eradicate Candida as part of selective decontamination of the digestive tract
      (SDD) protocols, but its effectiveness is unknown. We aimed to determine the
      effectiveness of nebulised amphotericin B in eradicating Candida respiratory
      tract colonisation in patients receiving SDD. METHODS: We included consecutive
      mechanically ventilated patients during a four-year period. Microbiological
      screening was performed upon admission and twice weekly thereafter according to a
      standardised protocol. A colonisation episode was defined as the presence of
      Candida species in two consecutive sputum samples taken at least one day apart.
      To correct for time-varying bias and possible confounding, we used a multistate
      approach and performed time-varying Cox regression with adjustment for age,
      disease severity, Candida load at baseline and concurrent corticosteroid use.
      RESULTS: Among 1,819 patients, colonisation with Candida occurred 401 times in
      363 patients; 333 of these events were included for analysis. Decolonisation
      occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients
      receiving and not receiving nebulised amphotericin B, respectively. Nebulised
      amphotericin B was associated with an increased rate of Candida eradication
      (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median
      times to decolonisation were six and nine days, respectively. The incidence rate
      of ventilator-associated pneumonia, length of stay and mortality did not differ
      between both groups. CONCLUSIONS: Nebulised amphotericin B reduces the duration
      of Candida colonisation in the lower respiratory tracts of mechanically
      ventilated critically ill patients receiving SDD, but data remain lacking that
      this is associated with a meaningful improvement in clinical outcomes. Until more
      evidence becomes available, nebulised amphotericin B should not be used routinely
      as part of the SDD protocol.

PMID- 24119708
TI  - Risky behaviours among young people living with HIV attending care and treatment
      clinics in Dar Es Salaam, Tanzania: implications for prevention with a positive
      approach.
AB  - INTRODUCTION: Prevention with a positive approach has been advocated as one of
      the main strategies to reduce new instances of HIV infection. Risky sexual
      behaviours among people living with HIV/AIDS are the cornerstone for this
      approach. Understanding the extent to which infected individuals practice risky
      behaviours is fundamental in designing appropriate population-specific
      interventions. With the HIV infection transmission rates remaining high among
      young people in sub-Saharan Africa, continued prevention among them remains a
      priority. This study therefore seeks to describe the magnitude and determinants
      of risky sexual behaviours among young people living with HIV. METHODS: A cross
      sectional study was conducted between June and July 2010 in selected Care and
      Treatment Clinics (CTCs) in Dar Es Salaam, Tanzania. A total of 282 HIV-positive
      patients aged 15-24 were interviewed about their sexual behaviours using a
      questionnaire. RESULTS: Prevalence of unprotected sex was 40.0% among young males
      and 37.5% among young females (p<0.001). Multiple sexual partnerships were
      reported by 10.6% of males and 15.9% of females (p<0.005). More than 50% of the
      participants did not know about the HIV status of their sexual partners. A large
      proportion of participants had minimal knowledge of transmission (46.7% males vs.
      60.4% females) and prevention (65.3% males vs. 73.4% females) of sexually
      transmitted infections (STIs). Independent predictors of condom use included non
      use of alcohol [adjusted odds ratio (AOR), 0.40 95% confidence interval (CI);
      0.17-0.84] and younger age (15-19 years) (AOR, 2.76, 95% CI: 1.05-7.27). Being on
      antiretroviral therapy (AOR, 0.38, 95% CI: 0.17-0.85) and not knowing partners'
      HIV sero-status (AOR, 2.62, 95% CI: 1.14-5.10) predicted the practice of multiple
      sexual partnership. CONCLUSIONS: Unprotected sex and multiple sexual partnerships
      were prevalent among young people living with HIV. Less knowledge on STI and lack
      of HIV disclosure increased the vulnerability and risk for HIV transmission among
      young people. Specific intervention measures addressing alcohol consumption,
      risky sexual behaviours, and STI transmission and prevention knowledge should be
      integrated in the routine HIV/AIDS care and treatment offered to this age group.

PMID- 24119709
TI  - Membrane assisted micro-solid phase extraction of pharmaceuticals with amino and
      urea-grafted silica gel.
AB  - Individual polar sorbents with surface-displayed amino groups (APS) and non
      nucleophilic urea-groups (UPS), were prepared by chemical modification of
      granular silica gel with bifunctional silane coupling reagents. In this
      preliminary study, they were separately employed for micro-solid phase extraction
      (MU-SPE) of the quarternary salt of Amitriptyline (Ami), Carbamazepine (Cbz),
      Ketoprofen (Ket) and Diclofenac (Dfn) from aqueous samples in conjunction with
      high performance liquid chromatography. The resulting enrichment factors for both
      APS and UPS are comparable and exceeded those of MU-SPE involving commercial C18
      silica gel sorbents. The presence of highly polar, but non-basic and non
      nucleophilic surfaces on UPS prompted the development of a UPS-based MU-SPE
      method. Good linear correlation was found over a concentration range of 0-50 MUg
      L(-1) with limits of detection ranging from 0.66 to 2.36 MUg L(-1)). Limits of
      quantification between 1.61 and 7.88 MUg L(-1) were obtained. HPLC analyses
      indicated that relative recoveries of 123% for Ami, 65.6% for Cbz, 71.2% for Ket
      and 66.5% for Dfn were obtained during MU-SPE of spiked (10 MUg L(-1))
      environmental water samples with percentage relative standard deviations (%RSD)
      of between 2.1% and 12.6%.

PMID- 24119710
TI  - Effects of heavy metal accumulation on some reproductive characters in
      Armadillidium granulatum Brandt (Crustacea, Isopoda, Oniscidea).
AB  - The impact of heavy metal bioaccumulation on reproduction of the isopod
      Armadillidium granulatum was studied by exposing the animals to food contaminated
      with various sub-lethal concentrations of cadmium, lead and zinc salts over a
      period of three weeks. The analysis carried out by atomic absorption spectrometry
      on whole body and on isolated female and male genital systems highlighted that,
      although metal's bioaccumulation was always concentration-dependent, it varies
      considerably depending on the metal (Cd>Zn>Pb) as pointed out by the respective
      values of the concentration factor. The heavy metals bioaccumulation has
      influenced in different ways the reproductive characters observed; while no
      significant difference was found with regard to the length of the incubation
      period and the number of broods--A. granulatum has an iteroparous reproductive
      strategy--the onset and the length of the reproductive season were negatively
      affected by the increase in concentration of the tested metals, in particular of
      Cd. The rate of gravid females, instead, was negatively affected by the
      bioaccumulation of Cd and Zn while in the groups treated with the highest
      concentrations of Pb all females produced at least one brood. The number of
      juveniles released from the brood pouch at the end of incubation resulted
      considerably higher and it was always positively correlated to the increase of
      the concentration of each metal, except for the highest Pb concentration. The
      explanation of this result, apparently anomalous, could be the object of a future
      research.

PMID- 24119711
TI  - The association between CHRN genetic variants and dizziness at first inhalation
      of cigarette smoke.
AB  - Numerous single nucleotide polymorphisms (SNPs) in multiple nicotinic receptor
      genes (CHRN) are associated with smoking. However few studies have examined the
      association between CHRN SNPs and subjective responses to smoking in adolescents
      which may relate to sustained smoking, such as dizziness at first inhalation. The
      objective of this study was to investigate the association between 61 SNPs in
      eight CHRN genes (CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4)
      and dizziness at first inhalation. Data were available from a longitudinal cohort
      investigation of 1293 students 12-13year-old at baseline. Students completed self
      report questionnaires at school every 3months for 5years during secondary school,
      and a mailed questionnaire three years later. DNA extracted from blood or saliva
      was genotyped for 61 CHRN SNPs selected using a gene tagging approach.
      Associations were modeled using logistic regression controlling for sex, race and
      age at first cigarette. Complete data were available for 356 of 475 participants
      (75%) who initiated smoking. The minor alleles of three SNPs in CHRNA6
      (rs7812298, rs2304297, rs7828365) were associated with a decreased probability of
      dizziness (OR(95% CI)=0.54 (0.36, 0.81), 0.59 (0.40, 0.86) and 0.58 (0.36, 0.95),
      respectively), while one SNP in each of three other genes (rs3743077 (CHRNA3),
      rs755204 (CHRNA4), rs7178176 (CHRNA7)) was associated with an increased
      probability of dizziness (OR(95% CI)=1.40 (1.02, 1.90), 1.85 (1.05, 3.27) and
      1.51 (1.06, 2.15), respectively). Thus, several SNPs located in CHRN genes are
      associated with dizziness at first inhalation, a smoking initiation phenotype
      that may relate to sustained smoking.

PMID- 24119712
TI  - Non-substance addictive behaviors in the context of DSM-5.

PMID- 24119713
TI  - Advanced imaging in colonoscopy and its impact on quality.
AB  - Detecting and resecting colonic polyps during endoscopy has been shown to reduce
      CRC. At the same time, endoscopy has faced substantial technical improvements and
      continues to undergo major changes. Detection of colorectal neoplasias is
      facilitated by using high-definition endoscopy, and characterization of lesions
      is more accurate by using virtual CE. High-definition endoscopy has found
      widespread use, whereas virtual CE is still more often used in tertiary centers
      and for high-risk patient groups. Endomicroscopy has opened the door for in vivo
      histology and functional as well as molecular imaging. Thorough training of the
      endoscopists is necessary, and redefined reimbursement codes may help make these
      techniques available in the clinical arena for high-risk patients who are most
      probable to benefit from the more advanced diagnostic endoscopy techniques. Over
      recent years, there has also been an increasing push by healthcare payors and
      providers to improve the quality of healthcare services. The ultimate goal of
      monitoring quality measures is to improve the overall health of the population
      and, for colon cancer screening, to reduce the incidence and mortality of colon
      cancer. However, the development of an appropriate quality measure and ensuring
      the accuracy of the data on which we base our efforts are among the first
      challenges that we must meet (Table 1). The continued technologic advancements in
      colonoscopy and endoscopic imaging may result in improvements in the quality of
      colonoscopy and should lead to a decrease in the incidence and mortality from
      colon cancer.

PMID- 24119714
TI  - Comparison between two portable hemoglobinometers and a reference method to
      verify the reliability of screening in blood donors.
AB  - Portable hemoglobinometers are used to determine hemoglobin level, but there are
      conflicting reports regarding their accuracy. The aim of this study was to
      compare results from two portable hemoglobinometers (HemoCue(r) and Hemo-Control)
      with an automated hematology analyzer (Sysmex XE-2100D) to determine if the
      screening of blood donors is reliable. A total of 426 blood donors' samples were
      studied and on average the Hb content measured in capillary blood samples was
      higher than that found in venous blood samples. Hemoglobinometers can be employed
      as a method to screen blood donors, but critical values should be confirmed in an
      automated hematology analyzer.

PMID- 24119715
TI  - [New ASAS criteria for the diagnosis of spondyloarthritis: diagnosing
      sacroiliitis by magnetic resonance imaging].
AB  - Radiographic sacroiliitis has been included in the diagnostic criteria for
      spondyloarthropathies since the Rome criteria were defined in 1961. However, in
      the last ten years, magnetic resonance imaging (MRI) has proven more sensitive in
      the evaluation of the sacroiliac joints in patients with suspected
      spondyloarthritis and symptoms of sacroiliitis; MRI has proven its usefulness not
      only for diagnosis of this disease, but also for the follow-up of the disease and
      response to treatment in these patients. In 2009, The Assessment of
      SpondyloArthritis international Society (ASAS) developed a new set of criteria
      for classifying and diagnosing patients with spondyloarthritis; one important
      development with respect to previous classifications is the inclusion of MRI
      positive for sacroiliitis as a major diagnostic criterion. This article focuses
      on the radiologic part of the new classification. We describe and illustrate the
      different alterations that can be seen on MRI in patients with sacroiliitis,
      pointing out the limitations of the technique and diagnostic pitfalls.

PMID- 24119716
TI  - An investigation into the reliability and variability of wobble board performance
      in a healthy population using the SMARTwobble instrumented wobble board.
AB  - OBJECTIVES: There is clinical need to provide quantification of wobble board
      performance. This study aimed to investigate, in a healthy population, wobble
      board performance, using an instrumented wobble board. DESIGN: Experimental
      observational. SETTING: Clinical setting, Bournemouth University. PARTICIPANTS:
      Thirty-two healthy volunteers. MAIN OUTCOME MEASURES: Wobble board performance
      was measured using time spent in tilt angle bandings, on the edge and number of
      edge contacts. Time was normalised to total time, yielding time as a percentage.
      RESULTS: Mean (sd) intra-class correlation coefficients (ICC) for percentage-time
      in each banding was 0.71(0.1); 95% confidence interval (CI) (0.67-0.76)
      indicating good consistency with repeated performances. Mean (sd) standard error
      of measurement (SEM) for percentage-time was 4.2% (1.3%); 95% CI (3.6-4.7%)
      indicating small errors associated with repeated performances. Minimal detectable
      change was small for percentage-time in tilt bandings (5%) and number of edge
      contacts (9). One-way ANOVA demonstrated that eyes closed yielded significantly
      different results to all other conditions. Time in the outer tilt band, on the
      edge and number of edge contacts may be better at discriminating between tasks in
      healthy volunteers. CONCLUSIONS: The SMARTwobble board is reliable for measuring
      balance within a healthy population and provides reference for further clinical
      studies.

PMID- 24119717
TI  - Role of bursectomy for advanced gastric cancer: result of a case-control study
      from a large volume hospital.
AB  - AIMS: According to the recent Japanese Gastric Cancer Association's gastric
      cancer treatment guidelines, bursectomy is recommended for tumors penetrating the
      serosa of the posterior gastric wall. However, there is still little data to show
      whether bursectomy improves patient survival. The aim of this study is to
      evaluate the efficacy of bursectomy for subserosa or serosa-positive gastric
      cancer in terms of overall survival. METHOD: From April 2001 to December 2006,
      470 patients underwent curative resection for macroscopically subserosa or serosa
      positive gastric cancer. These patients were grouped according to whether
      bursectomy was performed or not (bursectomy+/bursectomy-). Clinicopathological
      characteristics and incidence of complications were compared between the groups.
      The overall survival rates were analyzed using a Cox proportional hazards model.
      RESULTS: There was no significant difference in morbidity and mortality between
      the bursectomy+ and bursectomy- groups. In the multivariable analysis for overall
      survival, bursectomy was not a significant independent factor (p = 0.978). In the
      subgroup analysis for clinical and pathological stage III and IV, and tumors
      penetrating the serosa of the posterior gastric wall, bursectomy did not have
      significant effect on overall survival as well (p = 0.582, 0.453, and 0.532,
      respectively). In the propensity score-matched patients, bursectomy still showed
      no significant effect on overall survival (p = 0.804). CONCLUSIONS: Bursectomy is
      unlikely to improve overall survival in patients with macroscopically subserosa
      or serosa-positive gastric cancer.

PMID- 24119718
TI  - Randomized controlled trial of alfacalcidol supplementation for the reduction of
      hypocalcemia after total thyroidectomy.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of perioperative
      alfacalcidol on postoperative hypocalcemia after total thyroidectomy. METHODS: A
      total of 219 patients scheduled for total thyroidectomy were randomized into
      groups not receiving (group A) or receiving (group B) perioperative alfacalcidol.
      Postoperative hypocalcemia was compared between groups on postoperative day (POD)
      1 and POD2. Patients with hypocalcemia (<2.00 mmol/L) received oral calcium
      supplementation. Calcium and vitamin D levels were measured at 5-week and 6-month
      follow-ups. RESULTS: The incidence of symptomatic hypocalcemia was significantly
      lower in group A (P = .02), whereas similarly low levels of calcemia were
      observed in both groups on POD1 (37% and 30%, respectively; P = not significant)
      and persisted on POD2 (14% and 6%, respectively; P = not significant). Patients
      with severe hypocalcemia (<1.90 mmol/L) showed faster recovery in group A
      compared with group B (6% vs 1%, P = .04). At 5 weeks, calcium and vitamin D
      levels were similar between the groups. Six months after surgery, 4% (group A)
      versus 0% (group B) of subjects exhibited permanent hypoparathyroidism (P = .04).
      CONCLUSIONS: Although the treatment did not correct vitamin D deficiency,
      perioperative alfacalcidol uptake resulted in decreased transient hypocalcemia
      and related symptoms in patients undergoing total thyroidectomy.

PMID- 24119719
TI  - Prognostic factors influencing event-free survival and treatments in desmoid-type
      fibromatosis: analysis from a large institution.
AB  - BACKGROUND: Prognostic factors and optimal management of desmoid tumors have been
      discussed for decades. The authors present the results of a large series of
      patients with desmoid tumors treated at a single institution to investigate the
      prognostic factors influencing event-free survival (EFS) and suitable treatments
      for these rare tumors. METHODS: Two hundred fourteen patients with desmoid tumors
      admitted to the surgical department were included, of whom 20 were recommended
      for a policy of watchful waiting. The following clinical parameters were studied:
      admission status, age, sex, tumor site, tumor size, margin status, and
      therapeutic strategy. Univariate and multivariate analysis were performed for
      EFS. RESULTS: Forty-two patients had local recurrence. One patient died of intra
      abdominal disease. The 5-year and 10-year EFS rates were 78.8% and 77.9%,
      respectively. In univariate analysis, admission status, tumor site, tumor size,
      and group (R0 vs R1 and R0 vs R2) had significant impacts on EFS. EFS discrepancy
      was not significant between R1 and R2 or biopsy groups. In multivariate analysis,
      tumor size and admission status had independent value. The median delay to
      progression for patients undergoing watchful waiting was comparable with that for
      the surgical group. CONCLUSIONS: This study demonstrates that tumor size and a
      history of recurrence are independent predictors of EFS. Surgery is warranted if
      it can be R0 and function sparing. Nonsurgical modalities or a policy of watchful
      waiting may be a better choice for unresectable disease.

PMID- 24119720
TI  - Post-extubation dysphagia in trauma patients: it's hard to swallow.
AB  - BACKGROUND: There is a significant incidence of unrecognized postextubation
      dysphagia in trauma patients. The purpose of this study was to evaluate the
      incidence, ascertain the risk factors, and identify patients with postextubation
      dysphagia who will require clinical swallow evaluation. METHODS: A prospective
      observational study was performed on 270 trauma patients. Bedside clinical
      swallow evaluation was done within 24 hours of extubation. Logistic regression
      analysis was used to adjust for confounding variables. RESULTS: The incidence of
      oropharyngeal dysphagia (OD) in our study was 42%. Ventilator days was the
      strongest independent risk factor for OD (3.6 vs 8.0, P < .001). The odds ratio
      showed a 25% risk for OD for each additional ventilator day. Silent aspiration
      was found in 37% of patients with OD. CONCLUSIONS: Trauma patients requiring
      mechanical ventilation for >=2 days are at increased risk for dysphagia and
      should undergo routine swallow evaluations after extubation.

PMID- 24119721
TI  - Routine upper gastrointestinal swallow studies after laparoscopic sleeve
      gastrectomy are unnecessary.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy has gained popularity among bariatric
      surgeons. The purpose of this study was to evaluate the usefulness of early upper
      gastrointestinal (UGI) contrast studies in the detection of postoperative
      complications. METHODS: Radiographic reports were reviewed from April 2006 to
      January 2013. During that time, 161 patients underwent laparoscopic sleeve
      gastrectomy. All patients were submitted to UGI examination on postoperative day
      (POD) 1. RESULTS: Among the 161 patients who underwent UGI, no contrast leaks
      were found on POD 1. Three patients (1.9%) developed stapler line leaks near the
      gastroesophageal junction, which were diagnosed on PODs 3, 4, and 10.
      Gastroesophageal reflux in 5 patients (3.1%) and delayed gastroesophageal transit
      in 10 patients (6.2%) were detected. CONCLUSIONS: The results of this study show
      that UGI series on POD 1 cannot assess the integrity of the gastric remnant.
      Early UGI series are not required as routine procedures in all operated patients.
      Computed tomographic swallow studies should be performed in patients who
      postoperatively develop clinical signs and symptoms of complications such as
      tachycardia, pain, or fever.

PMID- 24119723
TI  - Pharmacoeconomic analysis of the treatment of chronic hepatitis C with
      peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin in Spain.
AB  - BACKGROUND: An independent meta-analysis of randomized comparative trials of
      peginterferons alfa-2a and alfa-2b, both combined with ribavirin, analyzed the
      probability of achieving a sustained virological response (SVR). OBJECTIVE: To
      estimate the long-term cost-effectiveness of treatment of patients with chronic
      hepatitis C with peginterferon alfa-2a (180MUg/week) plus ribavirin (800
      1200mg/day) vs. alfa-2b (1.5MUg/kg/week) plus ribavirin (800-1400mg/day), from
      the perspective of the Spanish National Health System. METHODS: A Markov model
      was developed with 7 health states to simulate lifetime disease progression. SVR
      was calculated from the meta-analysis data. Transition probabilities and health
      state utilities were obtained from published literature. Direct healthcare costs
      were obtained from the drug catalog, while costs of disease-related complications
      were obtained from published studies and healthcare cost database. Costs were
      expressed in 2010?. The annual discount rate applied was 3.5% for both costs and
      benefits. RESULTS: SVR rate for treatment with alfa-2a was higher than with alfa
      2b; the differences were 6.0%, 7.6% and 8.7% for all genotypes, genotypes 1/4 and
      genotypes 2/3, respectively. Each patient would gain 0.469, 0.600 and 0.685 life
      years and 0.155, 0.198 and 0.227 quality-adjusted life-years with alfa-2a vs.
      alfa-2b, for the respective genotypes. The cost saving per patient treated with
      alfa-2a would be ?705, ?672 and ?1900, for all genotypes and for genotypes 1/4
      and 2/3, respectively, alfa-2a being dominant. CONCLUSIONS: According to the
      present model, treatment of patients with chronic hepatitis C with peginterferon
      alfa-2a is cost-effective compared with peginterferon alfa-2b, both combined with
      ribavirin.

PMID- 24119724
TI  - Clustering of attitudes towards obesity: a mixed methods study of Australian
      parents and children.
AB  - BACKGROUND: Current population-based anti-obesity campaigns often target
      individuals based on either weight or socio-demographic characteristics, and give
      a 'mass' message about personal responsibility. There is a recognition that
      attempts to influence attitudes and opinions may be more effective if they
      resonate with the beliefs that different groups have about the causes of, and
      solutions for, obesity. Limited research has explored how attitudinal factors may
      inform the development of both upstream and downstream social marketing
      initiatives. METHODS: Computer-assisted face-to-face interviews were conducted
      with 159 parents and 184 of their children (aged 9-18 years old) in two
      Australian states. A mixed methods approach was used to assess attitudes towards
      obesity, and elucidate why different groups held various attitudes towards
      obesity. Participants were quantitatively assessed on eight dimensions relating
      to the severity and extent, causes and responsibility, possible remedies, and
      messaging strategies. Cluster analysis was used to determine attitudinal
      clusters. Participants were also able to qualify each answer. Qualitative
      responses were analysed both within and across attitudinal clusters using a
      constant comparative method. RESULTS: Three clusters were identified. Concerned
      Internalisers (27% of the sample) judged that obesity was a serious health
      problem, that Australia had among the highest levels of obesity in the world and
      that prevalence was rapidly increasing. They situated the causes and remedies for
      the obesity crisis in individual choices. Concerned Externalisers (38% of the
      sample) held similar views about the severity and extent of the obesity crisis.
      However, they saw responsibility and remedies as a societal rather than an
      individual issue. The final cluster, the Moderates, which contained significantly
      more children and males, believed that obesity was not such an important public
      health issue, and judged the extent of obesity to be less extreme than the other
      clusters. CONCLUSION: Attitudinal clusters provide new information and insights
      which may be useful in tailoring anti-obesity social marketing initiatives.

PMID- 24119725
TI  - Unraveling the relationship between obesity, schizophrenia and cognition.
AB  - INTRODUCTION: Previous studies investigating the relationship between obesity and
      cognition as well as gender differences in these relationships reported equivocal
      results. Here, we examined age, years of education, schizophrenia, and gender
      differences which might affect the relationship between obesity and cognition.
      METHODS: 1012 healthy controls and 707 participants with schizophrenia were
      recruited. Information on body mass index (BMI) was obtained and a neurocognitive
      battery was administered. Structural equation modeling (SEM) was performed to
      examine the relationship between BMI, schizophrenia, cognition and its
      covariates. RESULTS: No significant direct effect of BMI on cognition was found
      when cognition was regressed on age, years of education, diagnosis of
      schizophrenia and BMI. Instead, two SEM models indicated that indirect effects
      between BMI and cognition exist. The indirect effect of BMI on cognition through
      schizophrenia was present in both genders, while the indirect effect of cognition
      on BMI through schizophrenia was only found in females. BMI affecting cognition
      through age, years of education and schizophrenia appears to be the most
      plausible model that explains the data. This indirect effect was larger in
      females and was masked by diagnosis of schizophrenia. CONCLUSION: With increased
      rates of obesity in schizophrenia, it is important to highlight the potentially
      deleterious effect of obesity on cognition. BMI could be used as a candidate risk
      marker to identify people at higher risk of cognitive deficits, and as an
      intervention target for modifications of cognitive outcomes.

PMID- 24119726
TI  - Mycobacterium bovis infection in cattle induces differential expression of
      prolactin receptor isoforms in macrophages.
AB  - Prolactin receptor (PRLr) is a member of the cytokine receptor superfamily 1
      showing tissue specific structural diversity. Expression of PRLr isoforms in
      lymphoid tissues has been associated with immunomodulatory function of prolactin.
      Bovine tuberculosis (bTB) is characterized by chronic inflammation caused by the
      persistent infection of lymphoid tissues with Mycobacterium bovis. To test the
      hypothesis of the influence of PRLr in the pathogenesis of bTB, the aim of this
      study was to identify PRLr isoforms expressed during bTB in different tissues and
      to analyze their association with the pathogenesis of bTB. We examined lymphoid
      and non-lymphoid tissues ex vivo from experimentally and naturally infected
      cattle, as well as from bTB-free cattle, by Western blot (WB) and
      immunohistochemistry (IH). In vitro, monocytes from exposed, infected, and
      healthy cattle were stimulated with M. bovis antigens and then analyzed by WB. To
      detect transcriptional levels of PRLr in macrophages (MO) exposed to M. bovis,
      real time PCR was performed. WB revealed diversity of PRLr isoforms in tissues
      from infected cattle but not in tissues from bTB-free cattle. PRLr isoforms 100
      kDa 75, 50 and 40 were found expressed in tissues of animals infected with M.
      bovis, while only the short isoform of 40 kDa correlated with the immunopathology
      and ability to infect MO. We confirmed the synthesis of PRLr mRNA in MO after M.
      bovis exposure and propose that molecular pathogen patterns of M. bovis might
      modulate inflammation during bTB through expression of the PRLr isoform in MO.

PMID- 24119727
TI  - Determinants of exclusive breastfeeding among mothers in Ghana: a cross-sectional
      study.
AB  - BACKGROUND: Mothers are encouraged to practice exclusive breastfeeding for the
      first six months of a child's life. The general objective of the study was to
      assess the predictors of exclusive breastfeeding among mothers in Ghana. METHODS:
      This was a cross-sectional study using data from the 2008 Ghana Demographic and
      Health Survey (GDHS). The study sample (n = 316) was based on infants (0-5 months
      old) during the survey period; extracted from the individual (women) data set.
      Binary logistic regression was used to examine the association between selected
      independent variables. RESULTS: In general, the rate of exclusive breastfeeding
      was 64 percent. Marital status, region and place of delivery were found to be
      associated with the practice of exclusive breastfeeding. The logistic regression
      model illustrated mothers from the Volta Region, those who delivered in a
      government health facility, and mothers who perceived their infants to be average
      in size were more likely to practice exclusive breastfeeding. CONCLUSION:
      Appropriate health education programmes by the Ministry of Health targeting
      mothers who are less likely to practice exclusive breastfeeding are recommended.

PMID- 24119728
TI  - Quantifying the effect of cardiorenal syndrome on mortality after left
      ventricular assist device implant.
AB  - BACKGROUND: Comorbidities complicate recovery and contribute to mortality after
      implant of a left ventricular assist device (LVAD). Coexistent cardiac and renal
      dysfunction (so-called cardiorenal syndrome) increases the risk of death, both
      with advanced heart failure and after LVAD implantation. We analyzed patients
      from the Interagency Registry for Mechanically Assist Circulatory Support to
      better estimate postimplant mortality according to the severity of renal
      dysfunction. METHODS: Patients with a continuous-flow LVAD were grouped according
      to their pre-implant level of renal dysfunction: severe was defined as dialysis
      and/or estimated glomerular filtration rate (eGFR) < 30 ml/min; moderate if eGFR
      was 30 to 59 ml/min or blood urea nitrogen (BUN) was > 60 mg/dl; and mild or no
      renal dysfunction if eGFR was >= 60 ml/min and BUN was < 60 mg/dl. RESULTS: Of
      the 4,917 patients with a continuous-flow LVAD implanted between June 2006 and
      March 2012, 3,160 (64%) were identified with mild or no renal dysfunction, 1,475
      (30%) with moderate dysfunction, and 282 (6%) with severe dysfunction. Worsening
      renal dysfunction correlated with decreased survival, with nearly a 20% reduction
      in the 2-year survival going from low to severe dysfunction. The major negative
      survival effect occurred during the first 3 months. Combination of severe renal
      dysfunction and cardiogenic shock predicted the highest early mortality.
      CONCLUSIONS: Pre-implant renal dysfunction predicts higher mortality after LVAD
      implant. The progressive reduction in survival with higher grades of renal
      dysfunction supports consideration of LVAD implant before cardiorenal syndrome is
      advanced. For patients with severe renal dysfunction and other major
      comorbidities, initial support with a temporary device while awaiting organ
      recovery before implanting a durable pump could be considered.

PMID- 24119729
TI  - Pre-operative health status and outcomes after continuous-flow left ventricular
      assist device implantation.
AB  - BACKGROUND: Health status predicts adverse outcomes in heart failure and cardiac
      surgery patients, but its prognostic value in left ventricular assist device
      (LVAD) placement is unknown. METHODS: We examined the association of pre
      operative health status, as measured by the Kansas City Cardiomyopathy
      Questionnaire (KCCQ), with survival and hospitalization after LVAD using the KCCQ
      score as a continuous variable and stratified by KCCQ score quartile plus missing
      KCCQ in 1,125 clinical trial participants who received the HeartMate II (Thoratec
      Corp, Pleasanton, CA) as destination therapy (n = 635) or bridge to
      transplantation (n = 490). RESULTS: The mean pre-operative KCCQ score was 29.4 +/
      18.7 among survivors (n = 719), and 27.1 +/- 18.3 (n = 406) in those who died.
      In time-to-event analysis for all available follow-up using health status as a
      continuous variable, the pre-operative KCCQ score did not correlate with overall
      mortality after LVAD implantation (p = 0.178). Small absolute differences were
      seen between the pre-operative KCCQ quartile and 30-day survival (Q4 95% vs. Q1
      89% vs. missing 87%; p = 0.0009 for trend), 180-day survival (Q4 83% vs. Q1 76%
      vs missing 79%; p = 0.060 for trend), and days hospitalized at 180 days (Q4 29.8
      +/- 25.6 vs. Q1 34.1 +/- 27.1 vs. missing 36.5 +/- 29.9 days; p = 0.009 for
      trend). CONCLUSION: Our findings suggest that pre-operative health status has
      limited association with outcomes after LVAD implantation. Although these data
      require further study in a diverse population, mechanical circulatory support may
      represent a relatively unique clinical situation, distinct from heart failure and
      other cardiac surgeries, in which heart failure-specific health status measures
      may be largely reversed.

PMID- 24119731
TI  - Low temperature MQ NMR dynamics in dipolar ordered state.
AB  - We investigate analytically and numerically the Multiple Quantum (MQ) NMR
      dynamics in dipolar ordered spin systems of nuclear spins 1/2 at low
      temperatures. We consider two different methods of MQ NMR. One of them is based
      on the measurement of the dipolar energy. The other method uses an additional
      resonance (pi/4)y-pulse after the preparation period of the standard MQ NMR
      experiment in solids and allows one to measure the Zeeman energy. Both considered
      methods are sensitive to the contribution of remote spins in the interaction and
      to the spin system structure. The QS method is sensitive to the spin number in
      the molecule while the PS method gives very similar time dependencies of the
      intensities of MQ coherences for different spin numbers. It is shown that the use
      of the dipolar ordered initial state has the advantage of exciting the highest
      order MQ coherences in clusters of 4m identical spins, where m=1,2,3,..., that is
      impossible to do with the standard MQ method. MQ NMR methods based on the dipolar
      ordered initial states at low temperatures complement the standard NMR
      spectroscopy for better studying structures and dynamic processes in solids. 

PMID- 24119730
TI  - Urinary output and fractional excretion of sodium and urea as indicators of
      transient versus intrinsic acute kidney injury during early sepsis.
AB  - INTRODUCTION: The pathophysiology of acute kidney injury (AKI) in sepsis is ill
      defined. We investigated parameters associated with low glomerular filtration,
      and their predictive value to discriminate transient from intrinsic septic AKI.
      METHODS: In 107 sepsis patients, AKI was defined by the Risk, Injury, Failure,
      Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum
      creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was
      defined as RIFLE R, I, or F on the first day evolving to no AKI or not,
      respectively, over the following 5 days. Fractional excretion of sodium (FENa),
      urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1)
      was determined. RESULTS: Including versus not including the urinary-output
      criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and
      FENGAL were lower in no AKI versus transient AKI when AKI was defined based on
      creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary
      output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was
      present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in
      those with high versus low fractional sodium excretion, but this was only in
      patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in
      patients without AKI. The negative predictive value for either intrinsic AKI or
      not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92%
      and 94.5% respectively. CONCLUSIONS: A low FENa and FEUrea is highly prevalent in
      the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending
      AKI than increase in serum creatinine. A combination of a high FENa and a low
      FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea
      is strongly predictive of transient AKI.

PMID- 24119733
TI  - [The biological function of auto-induced expression of the hepatitis C virus
      soluble core protein].
AB  - OBJECTIVE: To investigate the biological role of auto-induced expression of
      hepatitis C virus (HCV) core protein (protein C) using a recombinant protein in
      an in vitro cell-based system. METHODS: The PCR-amplified full-length HCV protein
      C gene (573 bp) was inserted into the pET28a prokaryotic expression vector. The
      recombinant plasmid was transformed into BL21(DE3)pLysS E. coli to achieve high
      concentration expression of the recombinant C protein by auto-induction. The
      recombinant protein C was purified by Ni-NTA affinity chromatography, and tested
      in a protein binding assay for its ability to bind the HCV NS3 protein. RESULTS:
      The transformed E. coli produced a large amount of recombinant protein C, as
      detected in the sonicated supernatant of the bacteria culture. The antigenic
      reactivity of the recombinant protein C was confirmed by western blotting.
      However, the recombinant protein C could not be purified by Ni-NTA affinity
      chromatography, but co-precipitated with the HCV NS3 protein. CONCLUSION: Soluble
      recombinant protein C was successfully expressed by auto-induction, and shown to
      interact with the HCV NS3 protein, which provides a novel insight into the
      putative biological activity of this factor in HCV-related molecular processes.
      Future studies of this recombinant HCV protein C's crystal structure and
      antigenicity may provide further clues to its biological function(s) and
      potential for clinical applications.

PMID- 24119734
TI  - [Clinical observations of sequential interferon therapy following complete
      response to telbivudine treatment in chronic hepatitis B patients].
AB  - OBJECTIVE: To investigate the therapeutic benefit of sequential interferon alpha
      1b (IFNa-1b) in patients with hepatitis B e antigen (HBeAg)-positive chronic
      hepatitis B (CHB) who showed early complete response to telbivudine (LdT)
      treatment, and to explore the clinical value of serum hepatitis B surface antigen
      (HBsAg) for predicting sustained virological response (SVR). METHODS: Twenty
      HBeAg+ CHB patients who had shown a complete response to LdT therapy before
      treatment week 52 were divided into two treatment groups: one continued on the
      LdT treatment for an additional 6 months, and the other switched to IFNa-1b for 6
      months. Each patient presented for follow-up examinations at 1, 2, 3, 6, 9, 12,
      18, 24, 30 and 36 months after treatment cessation. Serum levels of alanine
      aminotransferase (ALT) and creatinine were detected by an automated biochemical
      analyzer. HBV DNA load was determined by real-time PCR. HBsAg and HBeAg levels
      were assessed by chemiluminescence. RESULTS: The relapse rate was lower in the
      group treated with sequential IFN than in the group who continued LdT treatment
      (30% vs. 40%, P more than 0.05). The area under the receiver operating
      characteristic curve at week 24 (0.689) was significantly higher than at week 12
      and week 48 (0.652 vs. 0.545, P less than 0.05). Decline in serum HBsAg levels at
      week 24 were predictive of SVR after treatment cessation. Patients showing a
      decrease more than 1000 IU/ml in serum HBsAg levels at week 24 had a
      significantly higher SVR rate than the patients who showed a decrease less than
      1000 IU/ ml (90.9%(10/11) vs. 33.3%(3/9), P less than 0.05). At the end of
      treatment, patients showing a decrease less than 200 IU/ml of serum HBsAg levels
      had a significantly higher SVR rate than those showing more than 200 IU/ml (100%
      vs. 53.3%, P less than 0.05). CONCLUSION: Sequential IFNa-1b consolidation
      therapy does not reduce the rate of relapse after treatment cessation. However,
      patients with a decrease in serum HBsAg levels of more than 1000 IU/ml at
      treatment week 24 are more likely to achieve SVR.

PMID- 24119735
TI  - [Dynamic change of hepatitis B surface antigen expression in chronic hepatitis B
      patients during the natural recovery course and the short-term antivirus
      treatment].
AB  - OBJECTIVE: To investigate the dynamic quantitative changes in expression of
      hepatitis B virus (HBV) surface antigen (HBsAg) that occurs during the natural
      recovery course and the short-term antivirus treatment period of patients
      suffering from flares in chronic hepatitis B (CHB). METHODS: CHB patients
      presenting for treatment of flare-ups were randomly assigned to receive treatment
      with Entecavir antiviral (group A, n = 39) or to naturally resolve the acute
      condition (group B, n = 22). All patients MELD scores were calculated and HBsAg
      levels and HBV DNA loads were measured upon admission (baseline), at worst
      condition stage, and end of treatment/flare-up (discharge). Pairwise comparisons
      of intergroup differences were made to evaluate the change in the three disease
      parameters over time in response to the management approach. RESULTS: The levels
      of HBsAg were not significantly different between the two groups at baseline,
      worst-condition stage and discharge (group A: (3.68+/-0.45), (3.84+/-0.19) and
      (3.69+/-0.58) log10 cut-off index (COI) respectively; group B: (3.59+/-0.54),
      (3.47+/-0.76) and (3.43+/-0.68) log10 COI respectively; all P more than 0.05).
      However, the HBV DNA loads were significantly lower in group A than in group B at
      the worst-condition stage and at discharge (all P less than 0.05). In group A,
      the MELD scores were significantly higher at baseline and at worst-condition
      stage than at discharge (all P = 0.000), but the difference between baseline and
      worst-condition stage was not significant. Also in group A, the HBV DNA load
      showed a gradually decreasing trend over time (baseline more than worst-condition
      stage more than discharge, all P less than 0.05). No significant differences were
      observed over time in the HBsAg levels of group A. In group B, the MELD scores
      were significantly higher at baseline and at worst-condition stage than at
      discharge (all P = 0.000), but the difference between baseline and worst
      condition stage was not significant (P = 0.619). Also in group B, the HBV DNA
      loads were significantly higher at baseline and worst-condition stage than at
      discharge (P = 0.000 and P = 0.003 respectively), but the difference between
      baseline and worst-condition stage was not significant. Finally, no significant
      differences were observed over time in the HBsAg levels of group B. CONCLUSION:
      Natural recovery from an acute flare-up of CHB is not accompanied by a change in
      HBsAg levels. In addition, short-term antiviral treatment to resolve the flare-up
      has no influence on HBsAg level.

PMID- 24119736
TI  - [Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein
      titer in infants born to mothers with positivity for hepatitis B surface
      antigen].
AB  - OBJECTIVE: To conduct a prospective randomized controlled trial of infants born
      to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to
      investigate the dynamic changes in the titer of anti-HBV surface protein (HBS)
      induced by treatment with combined immunoprophylaxis (200 IU hepatitis B
      immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to
      compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide
      an immunization strategy, monitoring mode and booster immunization schedule for
      the high-risk group. METHODS: Two-hundred-and-sixty-nine infants born to HBsAg
      positive mothers were given combined immunoprophylaxis at birth, and the venous
      blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load,
      and HBsAg and anti-HBS titers. RESULTS: The overall 1-year protective rate of
      combined immunoprophylaxis was 95.9%. There was no significant difference between
      the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine
      (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1
      mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest
      point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of
      infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than
      10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less
      than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to
      15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was
      higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P =
      0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was
      significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at
      12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was
      also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001).
      CONCLUSION: Combined immunoprophylaxis is therapeutically efficacious for
      treating infants born to HBsAg positive mothers. Monitoring these infants' anti
      HBs titer will help to identify non- or low-responders in a timely manner. The
      high-dose hepatitis B vaccine is preferable to the low-dose, and should be
      considered for use in immunization strategies for these infants.

PMID- 24119737
TI  - [Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine
      imbalance in vitro].
AB  - OBJECTIVE: To study the immunoregulatory effect of hepatitis B virus (HBV) e
      antigen (HBeAg) on peripheral blood monocytes (PBMCs). METHODS: PBMCs were
      isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and
      healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes
      in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in
      secreted cytokines were measured by enzyme-linked immunosorbent assay of the
      supernatants. Comparisons between two groups were made by the independent-samples
      t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was
      evaluated by Spearman's correlation analysis. RESULTS: Exposure to HBeAg led to a
      significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for
      both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190
      respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy
      controls' samples, the HBeAg exposure led to increased levels of secreted
      cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and
      t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC
      specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05
      respectively). Compared to the HBeAg-negative CHB patients' and healthy controls'
      samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell
      specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01
      respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and
      4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD
      1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and
      of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than
      0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was
      significantly higher in the samples from HBeAg- CHB patients than from the
      healthy controls (t = 3.214, P less than 0.01). CONCLUSION: HBeAg was able to
      down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate
      the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD
      L1on monocytes. These changes are conducive to the formation of immune tolerance
      to HBV. Therefore, HBeAg may play an important role in immune tolerance to
      chronic HBV infection.

PMID- 24119738
TI  - [Hepatitis B e antigen perturbs the LPS-stimulated production of inflammatory
      cytokines by mononuclear-derived dendritic cells].
AB  - OBJECTIVE: To investigate whether hepatitis B e antigen (HBeAg) can modulate the
      ability of dendritic cells (DCs) to produce inflammatory cytokines (IL-12/IL-6)
      upon stimulation in vitro. METHODS: Purified adherent mononuclear cells isolated
      by Ficoll-hypaque density gradient centrifugation were cultured in complete
      medium containing granulocyte macrophage colony-stimulating factor plus
      interleukin (IL)-4 to generate immature (i)DCs. Microscopic analysis and flow
      cytometry were performed to define the phenotypic characteristics of the iDCs.
      Then, different concentrations (1, 2 and 5 mug/ml) of HBeAg were added to the
      culture medium and for 24 hrs of incubation. To induce iDCs' maturation, the
      various groups of cells were incubated for 24 hrs in differentiation culture with
      lipopolysaccharide (LPS). Effects on secreted inflammatory cytokines were
      determined by enzyme-linked immunosorbent assay of the cells' supernatants.
      RESULTS: All concentrations of HBeAg led to significant reductions in IL-6 (all P
      less than 0.05). Similar significant reduction trends were seen for IL-12 at the
      HBeAg concentrations of 2 and 5 mug/ml (both P less than 0.05), but not at the 1
      mug/ml concentration. CONCLUSION: HBeAg may suppress the production of cytokines
      from DCs; this mechanism may contribute to the immune escape of HBV that supports
      persistent infection.

PMID- 24119739
TI  - [Clinical features of antiviral therapy in 12 patients with hepatitis C virus
      related cirrhosis after splenectomy].
AB  - OBJECTIVE: To evaluate the therapeutic effects and influencing factors of common
      antiviral therapy (low-dose interferon plus ribavirin, IFN+RBV) in patients with
      hepatitis C virus (HCV)-decompensated cirrhosis following splenectomy. METHODS:
      Twelve patients were treated post-surgery with low-dose IFN (300-500 MIU QOD) or
      pegylated (Peg)-IFN (50 mug/w) and RBV (0.6-0.9 g/d) for 72 weeks if carrying the
      lb genotype or 48 weeks if carrying the 2a genotype. All patients were followed
      up for 24 weeks after treatment completion to determine the virological response
      (VR) rates, measured as rapid (R)VR, complete early (cE)VR, 24 hr (24)VR, and
      sustained (S)VR. Statistical comparisons were made using the t-test or rank sum
      test, and correlation analyses were made using the Chi-square test. Differences
      were considered significant at P less than 0.05. RESULTS: All 12 patients
      completed the treatment course and follow-up. Three patients could not tolerate
      the Peg-IFN and were switched to IFN, and six patients developed hemolysis that
      required RBV dose adjustment. The VR rates were: 25.0%, RVR; 50.0%, cEVR; 16.7%,
      24VR; 86.0%, SVR. Only one patient was a non-responder, and only one relapsed. Of
      the patients who achieved SVR, 100% had shown RVR, 83.3% showed cEVR, and 50.0%
      showed 24VR, suggesting that RVR and cEVR may effectively predict SVR.
      CONCLUSION: Some HCV-decompensated cirrhosis patients may benefit from antiviral
      therapy following surgical resolution of hypersplenism. The occurrence of RVR and
      cEVR in these patients is positively correlated with achieving SVR. Physician
      patient communication during early antiviral treatment and close clinical
      monitoring accompanied by psychological counseling throughout promotes success of
      the treatment approach.

PMID- 24119740
TI  - [Clinical value of acoustic radiation force impulse imaging for quantitative
      evaluation of degree of liver fibrosis in chronic hepatitis C patients].
AB  - OBJECTIVE: To investigate the diagnostic value of acoustic radiation force
      impulse (ARFI) imaging technology for the assessment of liver fibrosis in chronic
      hepatitis C (CHC) patients. METHODS: One-hundred-and-eight CHC patients were
      examined by real-time ultrasound elastography using the Acuson S2000 ARFI
      instrument (Siemens Healthcare) and underwent liver biopsy for pathohistological
      analysis. The correlation between liver fibrosis grades determined by the two
      approaches was analyzed. The cut-off values for diagnosis by ARFI (S more than 2,
      S more than 3 and S = 4) were determined by generating a receiver operating
      characteristic (ROC) curve. RESULTS: The spectrum of liver stiffness detected by
      ARFI sonoelastography included S1 at (1.26+/-0.27) m/s (n = 36), S2 at (1.45+/
      0.51) m/s (n = 31), S3 at (2.01+/-0.54) m/s (n = 27), and S4 at (2.28+/-0.82) m/s
      (n = 14). The ARFI values were significantly different among the four different
      stages of liver fibrosis (P less than 0.001). The liver stiffness detected by
      ARFI sonoelastography was significantly correlated with the liver fibrosis stage
      determined by the gold standard pathohistological analysis (Spearman's rank
      coefficient: 0.61, P less than 0.001). Using the ARFI technology for assessment
      of liver fibrosis gave areas under the ROC curve of 0.779 for S more than 2
      patients, of 0.863 for S more than 3 patients, and of 0.0880 for S = 4 patients.
      CONCLUSION: The real-time ultrasound elastography ARFI technology can show the
      elasticity modulus of liver, and its data values positively correlate with the
      patho-histology grade of liver fibrosis in CHC patients. ARFI technology is easy
      to operate, non-invasive, and quantitative, and has potential clinical value for
      assessing liver fibrosis in CHC.

PMID- 24119741
TI  - [Establishment of a high metastatic potential human hepatocellular carcinoma
      orthotopic transplantation model with palliative liver resection in nude mice].
AB  - OBJECTIVE: To construct a high metastatic potential human hepatocellular
      carcinoma (HCC) orthotopic transplantation model with palliative liver resection
      in nude mice. METHODS: A human HCC orthotopic nude mice model was established by
      administering a single inoculation of the highly metastatic MHCC97H tumor tissue
      (size 2 mm * 2 mm * 2 mm) into the left liver lobe. At day 14 post-inoculation, a
      random group of the mice received palliative liver resection; the unresected mice
      served as controls. Changes in expression levels of 113 genes with metastasis
      related functions were evaluated in the residual HCC tissues. At day 35 post
      resection, a random group of the mice were sacrificed by cervical dislocation and
      a comprehensive metastases examination was performed. The remaining mice were
      used to observe life span. All statistical analyses were performed by the SPSS
      v17.0 software, and significance was defined as P less than 0.05. RESULTS: The
      nude mouse model of highly metastatic HCC with palliative liver resection was
      successfully established. Incidences of intrahepatic and abdominal metastases
      were higher in the palliative resected group (vs. unresected group: 11.7+/-4.7
      vs. 6.3+/-2.8, t = -2.412, P less than 0.05 and 9.8+/-3.4 vs. 5.2+/-2.6, t = 
      2.641, P less than 0.05 respectively). In addition, the palliative resected group
      showed significantly enhanced pulmonary metastasis (vs. unresected group: 14.3+/
      4.7 vs. 8.7+/-4.7, t = -2.348, P less than 0.05). Differential gene expression
      levels were found for MTSS1, TGFbl, SMAD2, IL-1b, and MMP7, and were situated in
      the central position of gene function net of residual HCC. The life-span of the
      palliative resected group was significantly longer than that of the unresected
      group (60.8+/-2.7 vs. 51.3+/-1.4 days, x2 = 12.850, P less than 0.01).
      CONCLUSION: The highly metastatic human HCC nude mouse model with palliative
      liver resection that was successfully constructed in this study represents a
      useful investigational tool to assess the biological characteristics of residual
      cancer and to screen therapeutic strategies.

PMID- 24119742
TI  - [miR-378 suppresses HBV-related hepatocellular carcinoma tumor growth by directly
      targeting the insulin-like growth factor 1 receptor].
AB  - OBJECTIVE: To investigate the impact and mechanism of microRNA (miR)-378 on
      hepatocellular carcinoma (HCC) cell growth. METHODS: The human hepatoma cell line
      HepG2 and its derivative HepG2.2.15 (stably expressing hepatitis B virus (HBV))
      were transduced with lentiviruses expressing miR-378 or non-expressing controls
      (nc-Lv). Effects on cell proliferation were assessed by the MTT assay and on
      colony-formation efficiency by clonogenic assay. Targets of miR-378 were
      predicted by bioinformatic analysis and validated by luciferase reporter assay in
      the human embryonic kidney cell line HEK293. Real-time polymerase chain reaction
      and western blotting were used to monitor expression of the endogenous targets in
      miR-378- overexpressing HepG2 and HepG2.2.15 cells. RESULTS: The HepG2 and
      HepG2.2.15 cells transduced with lentivirus expressing miR-378 showed
      significantly lower cell proliferation and colony formation than the control
      cells transduced with nc-Lv (P less than 0.01 and P less than 0.05,
      respectively). The insulin-like growth factor 1 receptor (IGF1R) was predicted as
      a potential target of miR-378, and luciferase reporter activity of IGF1R was
      significantly decreased in the HEK293 cells co-transfected with miR-378 (by 41.8%
      vs. the control cells, P less than 0.01). Moreover, the miRNA-378-mediated effect
      was narrowed down to the 3'-untranslated region (UTR) of IGF1R. The miRNA-378
      mediated reduction of IGF1R specifically involved its protein expression (P less
      than 0.01) and not its mRNA expression (P more than 0.05). CONCLUSION: miR-378
      may suppress growth characteristics of HBV-related HCC by directly targeting the
      IGF1R 3'-UTR and inhibiting its protein expression.

PMID- 24119743
TI  - [Hepatitis B virus X promotes HepG2 cell cycle progression and growth via
      downregulation expression of p16 protein].
AB  - OBJECTIVE: To investigate the effects and related mechanisms of hepatitis B virus
      X (HBx) protein on cell cycle and growth in hepatocellular carcinoma. METHODS: A
      human hepatocyte HepG2 cell line stably expressing a green fluorescent protein
      (GFP)-tagged HBx (HepG2/GFP-HBx cells) was used for the experiment, and HepG2
      parental and HepG2/GFP cells was used as the controls. Effect of HBx on cell
      growth was evaluated by the MTT cell proliferation assay and on cell cycle
      progression by flow cytometry analysis of cells with or without treatment with 5
      aza-2'-deoxycytidine (5-Aza-CdR; 5 pmol/L). Effect of HBx expression on promoter
      methylation status of the p16INK4A tumor-suppressor gene was detected by
      methylation-specific polymerase chain reaction and on p16 protein level was
      analyzed with western blotting. RESULTS: The HepG2/GFP-HBx cells showed
      significantly higher cell proliferation at 72 hrs of culture (3.225+/-0.038 A490)
      than either control (HepG2: 2.012+/-0.022 A490, t = -46.86, P less than 0.001;
      HepG2/GFP: 2.038+/-0.029 A490, t = 42.51, P less than 0.001). The HepG2/GFP-HBx
      cells also showed significantly lower proportion of cells in the G0/G1 phase
      (16.45%+/-0.45%) than either control (HepG2: 44.81%+/-1.36%, t = -34.202, P less
      than 0.001; HepG2/GFP: 42.76%+/-1.58%, t = -28.88, P less than 0.001). However, 5
      Aza-CdR treatment did lead to a significant amount of HepG2/GFP-HBx cells being
      arrested in the G0/G1 phase (33.25%+/-0.79%, t = 31.85, P less than 0.001). The
      p16INK4A promoter was methylated in the HepG2/GFP-HBx cells, and became
      demethylation after treatment with 5-Aza-CdR. However, no methylation of p16INK4A
      promoter was observed in both HepG2 and HepG2/GFP cells. The p16 protein level
      was significantly lower in the HepG2/GFP-HBx (vs. HepG2 and HepG2/GFP cells) and
      this level increased after treatment with 5-Aza-CdR. CONCLUSION: HBx protein
      promotes hepatocellular carcinoma cell cycle progression and growth by shortening
      the G0/G1 phase, and the underlying mechanism may involve inducing p16INK4A
      promoter methylation and downregulating p16 protein expression.

PMID- 24119744
TI  - [Polymorphism rs738409 in PNPLA3 is associated with inherited susceptibility to
      non-alcoholic fatty liver disease].
AB  - OBJECTIVE: To study the relationship between the patatin-like phospholipase
      domain-containing protein 3 (PNPLA3) gene and hereditary susceptibility to non
      alcoholic fatty liver disease (NAFLD) by detecting single nucleotide
      polymorphisms (SNPs). METHODS: Peripheral blood DNA from 315 patients diagnosed
      with NAFLD (including the spectrum of simple steatosis (SS) and non-alcoholic
      steatosis (NASH)) and 336 control subjects was used to determine the PNPLA3
      genotype by polymerase chain reaction (PCR) and direct sequencing. The
      relationship of SNPs and NAFLD-related markers of liver function were assessed by
      correlation analysis. RESULTS: The SNP rs738409 was identified in more of the
      NAFLD patients (allele variant frequencies: NAFLD, 65.40%; NASH: 71.87%; SS,
      56.47%) than in the controls (33.18%). Case-control analysis revealed that
      carriers of the 148GG genotype were at 3.81-fold (95% CI: 3.03 ~ 4.79) higher
      risk of developing NAFLD and at 1.97-fold (95% CI: 1.41 ~ 2.75) higher risk of
      progressing from SS to NASH, compared with non-carriers. rs738409 was also found
      to be associated with serum levels of alanine aminotransferase (ALT) and y
      glutamyltransferase (y-GT) (both P less than 0.05). Carriers of the 148GG
      genotype had significantly higher body mass index, ALT, and fasting insulin than
      carriers of the 148CC genotype (all P less than 0.05), and significantly higher
      level of serum HDL than carriers of either the 148CC genotype or the 148GC
      genotype (both P less than 0.05). CONCLUSION: Polymorphisms in the PNPLA3 gene
      may play an important role in mediating susceptibility to developing NAFLD in the
      Chinese population. The rs738409 polymorphism, in particular, is related to
      development and progression of NAFLD and may play a role in the contribution of
      PNPLA3 to NAFLD pathogenesis.

PMID- 24119745
TI  - [Hepatitis B surface antigen affects the expression of lipid metabolism-related
      genes in HepG2 cells].
AB  - OBJECTIVE: To investigate the influence of hepatitis B virus (HBV)-encoded small
      surface protein (SHBs) on hepatic cell expression of host genes related to lipid
      metabolism. METHODS: The full-length SHBs gene was amplified from HBV genotype C
      by polymerase chain reaction (PCR) and cloned into the pcDNA3.1(+) expression
      vector for stable transfection into HepG2 cells (selected by G418 screening);
      cells transfected with empty vector served as control. The SHBs mRNA and protein
      levels were detected by reverse transcription-PCR and enzyme-linked immunosorbent
      assay. SHBs effects on expression of genes and proteins related to lipid
      metabolism were detected by real-time quantitative (q)PCR and western blotting,
      respectively. RESULTS: The stably transfected cell line HepG2-pn3.1-SHBs was
      established successfully. qPCR showed that the HepG2-pn3.1-SHBs cells had
      significantly down-regulated transcription of the ECHS1, APOA1 and LPL genes
      (0.161+/-0.043 vs. control cells: 0.210+/-0.022, t = 2.479; 0.031+/-0.007 vs.
      0.094+/-0.055, t = 2.752; 0.770+/-0.036 vs. 0.982+/-0.031, t = 10.914), but
      significantly up-regulated ACC and SREBP-1c genes (0.113+/-0.027 vs. 0.059+/
      0.022, t = -3.757; 0.019+/-0.002 vs. 0.015+/-0.001, t = -4.330). The CPT1a and
      PPARa genes' expression was slightly, but not significantly, down-regulated in
      the HepG2-pn3.1-SHBs cells (0.028+/-0.005 vs. 0.030+/-0.004, t = 1.022; 0.014+/
      0.004 vs. 0.015+/-0.002, t = 0.758). Western blotting showed similar expression
      trends for the corresponding proteins. CONCLUSION: SHBs alters the expression of
      some host genes with known functions in fatty acid synthesis and decomposition;
      however, it remains unclear whether the hepatitis B surface antigen can directly
      contribute to development of hepatic steatosis.

PMID- 24119746
TI  - [Pleiotrophin stimulates growth and albumin secretion of rat hepatocytes in
      culture].
AB  - OBJECTIVE: To investigate the influence of pleiotrophin (PTN) on the growth of
      rat hepatocytes. METHODS: Primary rat hepatocytes were isolated from male Sprague
      Dawley rats and divided into three groups: group A (negative control), cultivated
      in normal culture medium; group B (positive control), cultivated with culture
      medium supplemented with supernatant from the embryonic fibroblast 3T3 cell line;
      group C (experimental), cultivated with culture medium supplemented with human
      recombinant (hr) PTN (100 ng/ml). The hepatocytes' growth rate and level of
      secreted albumin (ALB) were evaluated by microscopy and biochemical assay,
      respectively. Significance of between-group differences were assessed by one-way
      ANOVA, and pairwise comparisons were performed by the least significant
      difference test. RESULTS: The growth rates of hepatocytes in groups A, B and C
      were 2.800+/-0.084%, 4.300+/-0.132% and 3.800+/-0.053%, respectively. The growth
      rate of group B was significantly higher than the other two groups (F = 333.735,
      P less than 0.05). For all groups, the highest levels of secreted ALB were
      detected between the second and sixth day of culture, with g/L concentrations at
      day 2, 4 and 6 of: group A, 0.550+/-0.010, 0.900+/-0.030 and 0.300+/-0.040; group
      B, 0.900+/-0.030, 1.300+/-0.020 and 1.400+/-0.030; group C, 0.900+/-0.010,
      1.160+/-0.010 and 0.700+/-0.050. The secreted ALB of group B was significantly
      higher than that of the other two groups (F = 651.355, 338.831 and 863.205, P
      less than 0.05 ). CONCLUSION: PTN can benefit in vitro culturing of rat
      hepatocytes by stimulating growth and enhancing their ability to secrete albumin.

PMID- 24119747
TI  - Selection of reference genes from two leafhopper species challenged by
      phytoplasma infection, for gene expression studies by RT-qPCR.
AB  - BACKGROUND: Phytoplasmas are phloem-limited phytopathogenic wall-less bacteria
      and represent a major threat to agriculture worldwide. They are transmitted in a
      persistent, propagative manner by phloem-sucking Hemipteran insects. For gene
      expression studies based on mRNA quantification by RT-qPCR, stability of
      housekeeping genes is crucial. The aim of this study was the identification of
      reference genes to study the effect of phytoplasma infection on gene expression
      of two leafhopper vector species. The identified reference genes will be useful
      tools to investigate differential gene expression of leafhopper vectors upon
      phytoplasma infection. RESULTS: The expression profiles of ribosomal 18S, actin,
      ATP synthase beta, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      tropomyosin were determined in two leafhopper vector species (Hemiptera:
      Cicadellidae), both healthy and infected by "Candidatus Phytoplasma asteris"
      (chrysanthemum yellows phytoplasma strain, CYP). Insects were analyzed at three
      different times post acquisition, and expression stabilities of the selected
      genes were evaluated with BestKeeper, geNorm and Normfinder algorithms. In
      Euscelidius variegatus, all genes under all treatments were stable and could
      serve as reference genes. In Macrosteles quadripunctulatus, BestKeeper and
      Normfinder analysis indicated ATP synthase beta, tropomyosin and GAPDH as the
      most stable, whereas geNorm identified reliable genes only for early stages of
      infection. CONCLUSIONS: In this study a validation of five candidate reference
      genes was performed with three algorithms, and housekeeping genes were identified
      for over time transcript profiling of two leafhopper vector species infected by
      CYP. This work set up an experimental system to study the molecular basis of
      phytoplasma multiplication in the insect body, in order to elucidate mechanisms
      of vector specificity. Most of the sequences provided in this study are new for
      leafhoppers, which are vectors of economically important plant pathogens.
      Phylogenetic indications were also drawn from sequence analysis of these genes.

PMID- 24119748
TI  - Learning electrocardiogram on YouTube: how useful is it?
AB  - BACKGROUND: YouTube has become a useful resource for knowledge and is widely used
      by medical students as an e-learning source. The purpose of this study was to
      assess the videos relating electrocardiogram (ECG) on YouTube. METHODS: YouTube
      was searched on May 28, 2013 for the search terms "AF ecg" for atrial
      fibrillation, "AVNRT" for atrioventricular nodal reentrant tachycardia, "AVRT"
      for atrioventricular reentrant tachycardia, "AV block or heart block" for
      atrioventricular block, "LBBB, RBBB" for bundle branch block, "left anterior
      fascicular block or left posterior fascicular block" for fascicular blocks, "VT
      ecg" for ventricular tachycardia, "long QT" and "Brugada ecg". Non-English
      language, unrelated and non-educational videos were excluded. Remaining videos
      were assessed for usefulness, source and characteristics. Usefulness was assessed
      with using a checklist developed by the authors. RESULTS: One hundred nineteen
      videos were included in the analysis. Sources of the videos were as follows:
      individuals n=70, 58.8%, universities/hospitals n=10, 8.4% and medical
      organizations n=3, 2.5%, health ads n=10 8.4%, health websites n=26, 21.8%. Fifty
      six (47.1%) videos were classified as very useful and 16 (13.4%) videos were
      misleading. 90% of the videos uploaded by universities/hospitals were grouped as
      very useful videos, the same ratio was 45% for the individual uploads. There were
      statistically significant differences in ECG diagnosis among the groups (for very
      useful, useful and misleading, p<0.001, 0.02 and 0.008, respectively). The ratio
      of the misleading information in ventricular tachycardia videos was found to be
      42.9%. CONCLUSIONS: YouTube has a substantial amount of videos on ECG with a wide
      diversity from useful to misleading content. The lack of quality content relating
      to ECG on YouTube necessitates that videos should be selected with utmost care.

PMID- 24119749
TI  - Improved separation and detection of picolinic acid and quinolinic acid by
      capillary electrophoresis-mass spectrometry: application to analysis of human
      cerebrospinal fluid.
AB  - "Quinolinic acid (QA)", a metabolite of the kynurenine pathway (KP), is
      implicated as a major neurological biomarker, which causes inflammatory
      disorders, whereas there is an increase evidence of the role of picolinic acid
      (PA) in neuroinflammation. Therefore, there is an urgent need to develop new
      clinical test for early diagnosis of neuroinflammatory disorders. A comparison is
      made between three different platforms such as high performance liquid
      chromatography-electrospray mass spectrometry (HPLC-ESI-MS/MS), nano LC-Chip/ESI
      MS/MS, as well as the use of cationic (quaternary ammonium) and anionic
      (sulfonated) coated capillaries in capillary electrophoresis (CE)-ESI-MS/MS. The
      comparison revealed that CE-ESI-MS/MS method using a quaternary ammonium coated
      capillary is the best method for analysis of PA and QA. A simple stacking
      procedure by the inclusion of acetonitrile in the artificial cerebrospinal fluid
      (CSF) sample was employed to improve the peak shape and sensitivity of KP
      metabolites in CE-ESI-MS/MS. The developed CE-ESI-MS/MS assay provided high
      resolution, high specificity and high sensitivity with a total analysis time
      including sample preparation of nearly 12 min. In addition, excellent intra-day
      and inter-day repeatability of migration times and peak areas of the metabolites
      were observed with respective relative standard deviation (RSD) of less than 2.0%
      and 2.5%. Somewhat broader variations in repeatability for a 3 independently
      prepared coated capillary (total 35 runs each) with % RSD up to 3.8% and 5.8% was
      observed for migration time and peak areas, respectively. Artificial CSF was used
      as a surrogate matrix to simultaneously generate calibration curves over a
      concentration range of 0.02-10 MUM for PA and 0.4-40 MUM for QA. The method was
      then successfully applied to analyze PA and QA in human CSF, demonstrating the
      potential of this CE-ESI-MS/MS method to accurately quantitate with high
      specificity and sensitivity.

PMID- 24119750
TI  - Microextraction versus exhaustive extraction approaches for simultaneous analysis
      of compounds in wide range of polarity.
AB  - This article discusses comparison of microextraction versus exhaustive extraction
      approaches for simultaneous extraction of compounds in wide range of polarity at
      low and high volumes of sample by comparing solid phase extraction (SPE) and
      solid phase microextraction (SPME). Here, both systems are discussed
      theoretically and evaluated based on experimental data. Experimental comparisons
      were conducted in terms of extraction recovery, sensitivity, and selectivity for
      the extraction of doping agent compounds (logP: 0.14-4.98), using C18 as the
      extraction phase. The extraction recovery of both systems was studied at
      different volumes of phosphate buffered saline (PBS). The distribution constant
      of SPME in thin-film geometry (i.e., thin-film microextraction/TFME) as well as
      the retention factor and breakthrough volume for the SPE system were evaluated
      for the simultaneous extraction of polar and non-polar compounds. Using 1 mL of
      sample, the extraction recovery and sensitivity of the SPE system (100 mg
      sorbent) was comparable with that of TFME format of SPME (15 mg sorbent) for all
      analytes, with the exception of most polar compounds, due to the smaller amount
      of the extraction phase in SPME. Breakthrough in the SPE system was observed for
      more polar compounds in a 25 mL sample; however, this situation did not affect
      the quantitation of TFME, as this technique operates in equilibrium mode.
      Experimental values for breakthrough volume were in good match with the
      calculated theoretical values. Results indicate that the microextraction approach
      is more suitable for untargeted determinations, where the breakthrough volume
      cannot be determined prior to the experiment. In addition, when both methods are
      at optimum conditions, findings suggest that, despite the smaller volume of the
      extraction phase in TFME, the sensitivity of TFME can exceed that of SPE for
      samples where the target analytes vary substantially in polarity.

PMID- 24119751
TI  - Bioanalysis of therapeutic peptides: differentiating between total and anti-drug
      antibody bound drug using liquid chromatography-tandem mass spectrometry
      quantitation.
AB  - An acylated peptide with MW ~4.5 kDa was measured in samples from
      pharmacokinetic, toxicology and clinical studies using liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Lower limits of quantitation of 2 ng/mL and
      50 pg/mL were achieved for animal and human plasma, respectively. Repeated drug
      administration may lead to anti-drug antibodies (ADA) which can inactivate the
      drug by formation of drug-ADA complexes. Hence, the LC-MS/MS assay incorporated
      cleavage of potential drug-ADA complexes to quantify the total plasma
      concentration. To obtain information on active drug levels, an assay that
      measures the free concentration or alternatively the ADA-unbound concentration
      would be needed. Ultrafiltration experiments through 100 kD cutoff membranes to
      remove Ig-bound peptide were not successful due to nonspecific binding.
      Extraction of Ig-bound drug using Protein A or G (bacterial cell wall proteins
      with high affinity to the Fc region of IgG) was suitable to distinguish between
      ADA-bound drug and [free+protein bound (not ADA-bound)] drug and correlated with
      findings from ELISA ADA measurement.

PMID- 24119752
TI  - Graphene-epoxy composite electrode fabricated by in situ polycondensation for
      enhanced amperometric detection in capillary electrophoresis.
AB  - This report describes the development and application of a novel graphene-epoxy
      composite electrode as a sensitive amperometric detector of capillary
      electrophoresis. The composite electrode was fabricated on the basis of the in
      situ polycondensation of a mixture of graphene and 1,2-ethanediamine-containing
      bisphenol A epoxy resin in the inner bore of a piece of fused silica capillary
      under heat. The structure of the material was investigated by scanning electron
      microscopy, thermogravimetric analysis, X-ray diffraction, and Fourier transform
      infrared spectroscopy. The results indicated that graphene sheets were well
      dispersed and interconnected throughout the composite to form an electrically
      conductive network. The performance of this unique electrode was demonstrated by
      separating and detecting two naturally occurring phenolic compounds in rosemary
      in combination with capillary electrophoresis. The graphene-based detector
      offered significantly lower operating potentials, higher sensitivity,
      satisfactory resistance to surface fouling, and lower expense of operation,
      indicating great promise for a wide range of applications. 

PMID- 24119753
TI  - Imidazolium-based ionic liquid-type surfactant as pseudostationary phase in
      micellar electrokinetic chromatography of highly hydrophilic urinary nucleosides.
AB  - Ionic liquid (IL)-type surfactants have been shown to interact more strongly with
      polar compounds than traditionally used quaternary ammonium cationic surfactants.
      The aim of this study is to provide an alternative micellar electrokinetic
      chromatographic method (MEKC) for the analysis of urinary nucleosides in their
      ionic form at low surfactant concentration. This approach could overcome the use
      of high surfactant concentrations typically associated with the analysis of these
      highly hydrophilic metabolites as neutral species, which is frequently
      accompanied by high electric current, Joule heating and long analysis time. The
      investigated IL-type surfactant; 1-tetradecyl-3-methylimidazolium bromide
      (C14MImBr) is similar to the commonly employed cationic surfactant;
      tetradecyltrimethylammonium bromide (TTAB) but it provides a different separation
      selectivity. We employed C14MImBr micelles for the MEKC analysis of seven urinary
      nucleosides. The studied analytes possess a negative charge at pH 9.38
      (exceptions are adenosine and cytidine which are neutral at this pH value).
      Borate imparts an additional negative charge to these compounds after
      complexation with the cis-diol functionality of the ribose unit, which in turn
      enables them to interact with the oppositely charged C14MImBr micelles via
      electrostatic (Coulomb) forces. The effect of the concentration of borate (the
      complexing, competing and buffering ion) on the effective electrophoretic
      mobilities and on the retention factors was investigated. The effective
      electrophoretic mobility data show that complexation between these nucleosides
      and borate occurs with high degree of complexation even at very low borate
      concentration (2.5 mmol L(-1) disodium tetraborate). In addition, we found that
      the retention factors are strongly dependent on the borate concentration being
      the highest when using the lowest borate concentration and they can be regulated
      by variation of either tetraborate concentration or the pH of the background
      electrolyte using only 20 mmol L(-1) C14MImBr. We confirmed also that the main
      mode of interaction between these analytes and the C14MImBr micelles is
      electrostatic interaction. Our experimental results reveal that the cationic
      surfactant C14MImBr exhibits superior selectivity and higher reproducibility
      relative to that of TTAB, which makes this surfactant a promising cationic
      surfactant for the MEKC separation of other hydrophilic polar analytes.

PMID- 24119754
TI  - Amphiphilic block copolymer modified magnetic nanoparticles for microwave
      assisted extraction of polycyclic aromatic hydrocarbons in environmental water.
AB  - In this work, amphiphilic block copolymer poly(tert-butyl methacrylate)-block
      poly(glycidyl methacrylate) (PtBMA-b-PGMA) modified Fe3O4 magnetic nanoparticles
      (Fe3O4 MNPs) were synthesized, and served as an adsorbent for microwave-assisted
      extraction of polycyclic aromatic hydrocarbons (PAHs). The PtBMA-b-PGMA block
      copolymers with different block ratios were prepared by two-step atom transfer
      radical polymerization (ATRP) and the extraction abilities of their corresponding
      Fe3O4@PtBMA-b-PGMA were investigated. The key factors affecting the extraction
      efficiency of the adsorbent, including microwave conditions, amount of adsorbent,
      type and volume of desorption solvent, were studied in detail. In comparison with
      vortex, which is a conventional method used for assisting extraction, the
      proposed microwave-assisted method allowed better extraction efficiency and
      required a shorter extraction time. The calibration curves of PAHs were obtained
      in the range of 0.05-120 MUg/L (r>0.9985) and the limits of detection (S/N=3)
      were in the range of 2.4-6.3 ng/L. The recoveries of PAHs spiked in environmental
      water samples were between 62.5% and 104% with relative standard deviations
      (RSDs) ranging from 0.84% to 9.02%. The proposed technique combining microwave
      assisted extraction and magnetic separation was demonstrated to be a fast,
      convenient and sensitive pretreating method for PAHs.

PMID- 24119755
TI  - Separation of sulfoalkylated cyclodextrins with hydrophilic interaction liquid
      chromatography.
AB  - Determination of the charged state distributions of partially- and fully
      substituted sulfoalkylated cyclodextrins was achieved using hydrophilic
      interaction liquid chromatography (HILIC). HILIC analysis of a spiked sample of
      the partially sulfopropylated cyclodextrins was achieved using a gradient to
      baseline resolve the charged states from -1 to -14. The fully-substituted CDs
      yielded a major peak with some trace impurities and the partially-substituted
      sulfopropylated cyclodextrins showed a wide range of charge states present in the
      mixture. Small changes in the structure of the cyclodextrins have a significant
      impact on the retention times of the various types of cyclodextrins investigated.

PMID- 24119756
TI  - Metal-organic framework polymethyl methacrylate composites for open-tubular
      capillary electrochromatography.
AB  - Metal-organic frameworks (MOFs) are attractive as novel separation medium due to
      their distinguished properties including large surface area, accessible tunnels
      and diverse structures. Here, we report the incorporation of MOF CAU-1
      (CAU=Christian-Albrechts-University) into polymethyl methacrylate (PMMA) to
      produce a new composite (CAU-1@PMMA), and the fabrication of CAU-1@PMMA coated
      capillary for open tubular capillary electrochromatography (CEC). CAU-1 contains
      unprecedented [Al8(OH)4(OCH3)8](12+) clusters connected by twelve
      aminoterephthalic acid linkers, and is highly porous and stable in a variety of
      buffer solutions. The incorporation of CAU-1 into PMMA not only increases surface
      area, but also electroosmotic flow (EOF). As a result, the CAU-1@PMMA coated
      capillary column gives higher column efficiency, larger column capacity, and
      shorter separation time for baseline separation of two groups of aromatic
      carboxylic acids than the PMMA coated capillary column. Besides, the
      incorporation of CAU-1 also improves the resolution for the CEC separation of
      basic sulfa drugs and structurally related peptides. The run-to-run, day-to-day
      and column-to-column precision for the EOF of CAU-1@PMMA coated capillary column
      is 0.3%, 0.4%, and 2.2% (relative standard deviation), respectively. The results
      show that MOFs composites are promising stationary phases for CEC applications.

PMID- 24119757
TI  - Preparation of mesoporous silica embedded pipette tips for rapid enrichment of
      endogenous peptides.
AB  - Mesoporous silica embedded pipette tips (mSiO2-Tips) were successfully prepared
      by a simple method and applied to rapid enrichment of endogenous peptides for the
      first time. The prepared mSiO2-Tips showed low back pressure when solvent was
      pipetted up and down. As a result, mSiO2-Tip could selectively trap peptides and
      exclude high-MW proteins simultaneously based on size-exclusion mechanism due to
      the uniform mesopore structure of the sorbent bed. The in-pipette-tip SPE
      approach was proved to be easy-operation, sensitive and fast (less than 2 min)
      for the analysis of peptides, which was further successfully applied in the
      efficient enrichment of peptides from human plasma.

PMID- 24119758
TI  - Multi-capillary-column proton-transfer-reaction time-of-flight mass spectrometry.
AB  - Proton-transfer-reaction time-of-flight mass-spectrometry (PTR-TOFMS) exhibits
      high selectivity with a resolution of around 5000 m/Deltam. While isobars can be
      separated with this resolution, discrimination of isomeric compounds is usually
      not possible. The coupling of a multi-capillary column (MCC) with a PTR-TOFMS
      overcomes these problems as demonstrated in this paper for the ketone isomers 3
      heptanone and 2-methyl-3-hexanone and for different aldehydes. Moreover,
      fragmentation of compounds can be studied in detail which might even improve the
      identification. LODs for compounds tested are in the range of low ppbv and peak
      positions of the respective separated substances show good repeatability (RSD of
      the peak positions <3.2%). Due to its special characteristics, such as isothermal
      operation, compact size, the MCC setup is suitable to be installed inside the
      instrument and the overall retention time for a complete spectrum is only a few
      minutes: this allows near real-time measurements in the optional MCC mode. In
      contrast to other methods that yield additional separation, such as the use of
      pre-cursor ions other than H3O(+), this method yields additional information
      without increasing complexity.

PMID- 24119759
TI  - Investigation of the synergistic effect with amino acid-derived chiral ionic
      liquids as additives for enantiomeric separation in capillary electrophoresis.
AB  - Recently, chiral ionic liquids (ILs) have drawn more and more attention in chiral
      separation by capillary electrophoresis (CE). In this paper, two chiral ILs based
      on amino acid derivatives, L-alanine and L-valine tert butyl ester bis
      (trifluoromethane) sulfonimide, were applied for the first time in CE to evaluate
      their potential synergistic effects with classical chiral selectors (beta
      cyclodextrin derivatives) for enantiomeric separation. As observed, improved
      separation of tested drug enantiomers was obtained with the presence of chiral
      ILs compared to the conventional beta-cyclodextrin derivatives separation system.
      Parameters such as type and proportion of organic modifier, type and
      concentration of chiral ILs, concentration of chiral selector, buffer pH and
      applied voltage were systematically investigated with Me-beta-CD/chiral ILs as
      model system to optimize the novel synergistic system, and the best results were
      obtained when 15 mM chiral ILs were introduced into the 30 mM sodium
      citrate/citric acid (20% organic modifier included) buffer solution containing 20
      mM Me-beta-CD at pH 5.0 with a 20 kV applied voltage for naproxen, pranoprofen
      and warfarin.

PMID- 24119760
TI  - A new optimal sliding mode controller design using scalar sign function.
AB  - This paper presents a new optimal sliding mode controller using the scalar sign
      function method. A smooth, continuous-time scalar sign function is used to
      replace the discontinuous switching function in the design of a sliding mode
      controller. The proposed sliding mode controller is designed using an optimal
      Linear Quadratic Regulator (LQR) approach. The sliding surface of the system is
      designed using stable eigenvectors and the scalar sign function. Controller
      simulations are compared with another existing optimal sliding mode controller.
      To test the effectiveness of the proposed controller, the controller is
      implemented on an aluminum beam with piezoceramic sensor and actuator for
      vibration control. This paper includes the control design and stability analysis
      of the new optimal sliding mode controller, followed by simulation and
      experimental results. The simulation and experimental results show that the
      proposed approach is very effective. 

PMID- 24119761
TI  - The in vitro influences of epidermal growth factor and heregulin-beta1 on the
      efficacy of trastuzumab used in Her-2 positive breast adenocarcinoma.
AB  - BACKGROUND: Human epidermal growth factor receptor-2 (Her-2) is over expressed in
      approximately 25-30% of all primary breast tumors resulting in a distinctive
      breast cancer subtype associated with a poor prognosis and a decrease in overall
      survival. Trastuzumab (Herceptin(r)), an anti-Her-2 monoclonal antibody, has
      dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab
      is, however, associated with primary and acquired resistance. AIM AND METHODS: To
      investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium
      conversion assay), cell cycling (propidium iodide staining), apoptosis
      (executioner caspases and annexin-V) and relative surface Her-2 receptor
      expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and
      oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine
      potential augmentation of these effects by two endogenous ligands, epidermal
      growth factor (EGF) and heregulin-beta1 (HRG- beta1). RESULTS: Cell viability was
      decreased in SK-Br-3 cells by exposure to trastuzumab. This was associated with
      G1 accumulation and decreased relative surface Her-2 receptor density, supporting
      the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and
      heregulin-beta1 produced differential cell responses alone and in combination
      with trastuzumab, in some instances augmenting cell viability and cell cycling.
      Relative surface Her-2 receptor density was reduced substantially by trastuzumab,
      EGF and heregulin-beta1. These reductions were amplified when ligands were used
      in combination with trastuzumab. CONCLUSION: Cell type specific interactions of
      endogenous ligands appear to be dependent on absolute Her-receptor expression and
      cross activation of signaling pathways. This supports the notion that receptor
      density of Her-family members and multiplicity of growth ligands are of mutual
      importance in breast cancer cell proliferation and therefore also in resistance
      associated with trastuzumab.

PMID- 24119762
TI  - A longitudinal study revealing hepatitis E virus infection and transmission at a
      swine test station.
AB  - Hepatitis E virus (HEV) is a zoonotic agent that causes acute hepatitis in
      humans, and infects several animal species, most importantly swine. In the
      current study, that presents the first evidence of HEV infections in pigs in
      Finland, genetic divergence and transmission of HEV was investigated among pigs
      at a swine test station at two occasions. In 2007, HEV RNA was found in 25% of
      pens, and 35% of 2-3 month-old pigs at the station. Three different isolates,
      comprising 13 sequences of HEV genotype 3 e that were imported from different
      farms were detected. In 2010, 39% of pigs were HEV RNA positive on weeks 1, 3, or
      5 of a 3-month follow-up, and 11 sequences, all representing one of the isolates
      that was also present in 2007, were detected. The isolate was considered to be
      either re-introduced to, or to persist at the station, and it was transmitted
      between the pigs. The study sheds light on the rate and time of HEV transmission
      in swine, and describes the epidemiologic variability of HEV isolates over time.

PMID- 24119763
TI  - Alzheimer's disease: a gas model. The NADPH oxidase-Nitric Oxide system as an
      antibubble biomachinery.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease of unknown origin. The
      pathological lesions that define AD would be linked to the insidious accumulation
      of nitrogen, having invaded the brain interstitial fluid (ISF) from the blood via
      the physiological cycling pool of vascular glucose transporters (GLUT-1).
      According to this hypothesis, the nitrogen nanobubbles, being chemically inert
      and actually indestructible for human beings, can not escape from the ISF
      anymore. They would exert a huge and deleterious pressure against cellular
      components, especially in microglia and in astrocytes. They could enhance the
      existing cell oxygen anisotropy, which might enhance the natural bubble
      nucleation of O2-2O2 in cells or in mitochondria. Indeed, with the help of a new
      symbolic representation for gas nuclei in chemical reactions, the NADPH oxidase
      NO system is identified for the first time, as an antibubble biomachinery, able
      to break O2-2O2 bubbles up as it releases superoxide O2-. Superoxide is
      considered as a quantum bubble, which collapses through the reactivity of the
      gaseous NO radical. Their combination in soluble peroxinitrite provides the
      change from one state of matter to another, avoiding any risk of a bubble
      enlargement, and finally avoiding the risk of enzyme crowding or of a bulk
      pressure variation. However, a bubble is expected to entrap Nitric Oxide (NO),
      which leads theoretically to a decrease in its bioavailability, and is expected
      to trigger a guanylyl-cyclase-mediated inflammatory cascade, that could explain
      the inflammation in AD. In vitro, any increase in the hydrostatic pressure has
      already been linked to the microtubule disorganization. The amyloid deposits,
      also known as senile plaques, would behave as a sponge toward ISF nitrogen; Abeta
      is considered as a foam-stabilizing agent. By taking the shape of cerebral
      amyloid angiopathy, the amyloid could confine the nitrogen leak from the blood,
      and progressively insulate the Blood-Brain Barrier against the pollutant. All
      these theoretical features finally lead to the death of the neurons. The
      comprehensive statement of the theoretical pro-inflammatory action of inert gases
      is a real upheaval for the whole medicine.

PMID- 24119764
TI  - Bone morphogenic protein-4: a potential novel target for preventing vein graft
      failure in coronary revascularization.
AB  - Coronary artery bypass surgery is an effective and durable therapy in both acute
      coronary syndrome and chronic coronary stenotic disease refractory to
      pharmacological treatment. Despite rapid development in operation-specific
      technologies and secondary prevention measures, the benefits of surgical
      revascularization are largely limited by inadequate patency of one of the most
      commonly used conduits, namely the autologous saphenous vein. However, apart from
      antiplatelet and lipid-lowering drugs, no other pharmacologic agent has hitherto
      proven clinically effective in preventing short- and long-term vein graft
      failure. Aiming at a large number of known biomolecules, multiple promising
      strategies failed to translate their beneficial effects observed in animal models
      into the clinical settings. Bone morphogenic protein-4 (BMP4), originally
      identified as a mediator in bone formation, has been recently demonstrated to
      participate in the process of arterial post-injury remodeling. Existing evidence
      has demonstrated that BMP4 is closely involved in the pathogenesis of thrombus
      formation, neointimal hyperplasia and superimposed atherosclerosis, all of which
      significantly contribute to arterial stenotic lesions. Although the post-injury
      responses inherent to arterial and venous vessel are unique, they share common
      elements and present with similar physiologic characteristics and clinical
      sequelae. Therefore, with regard to the multifaceted effects of BMP4 in
      regulating arterial wall remodeling, we hypothesize that BMP4 may play an
      important role in mediating the pathological responses of the venous wall to the
      arterial circulation. If our hypothesis is demonstrated correct, BMP4 inhibition
      could presumably serve as a novel strategy for preventing vein graft failure in
      coronary revascularization. 

PMID- 24119765
TI  - Frequent yawning as an initial signal of fever relief.
AB  - Research suggests that yawning provides a brain cooling function in homeotherms,
      and that excessive yawning may be a useful diagnostic indicator of abnormal
      thermoregulation in humans. Accordingly, the frequency of yawning should increase
      during instances of hyperthermia, but not fever (i.e., pyrexia), since this
      represents an elevation in the homeostatic set point rather than thermoregulatory
      failure. To our knowledge, no research has investigated the association between
      yawning frequency and fever in humans. Here we present the hypothesis that
      frequent yawning could be used as an initial signal for fever relief, either
      through the effectiveness of antipyretics or the natural break of a fever.
      Applications of this research include the improved behavioral monitoring of
      patients. 

PMID- 24119766
TI  - Systemic corticosteroid treatment in Peyronie's disease.
AB  - Peyronie's disease is characterized by penile pain, plaque or indurated area in
      the tunica albugenia and penile curvature during erection. Peyronie's disease is
      a chronic and progressive inflammatory disease. Intralesional corticosteroids
      have been studied in the treatment of Peyronie's disease due to its inflammatory
      pathogenesis but hardness of the penile plaque hinders the effective injection
      and activity of the compound and leads to local side effects. Corticosteroids are
      the most effective therapy for many inflammatory disorders and systemic use has
      not been studied in Peyronie's disease. Oral corticosteroids may decrease the
      pain, improve the penile curvature, reduce the plaque size, and inhibit the
      formation of fibrosis particularly in the acute inflammatory phase. 

PMID- 24119767
TI  - Diagnoses associated with use of atypical antipsychotics in a commercial health
      plan: a claims database analysis.
AB  - BACKGROUND: Atypical antipsychotics are indicated for specific psychiatric
      conditions; however, they are frequently used for US Food and Drug Administration
      nonapproved indications. OBJECTIVE: This study assessed the types of medical
      diagnoses associated with atypical antipsychotic prescriptions in commercial
      health care plans. METHODS: This retrospective cohort study used the OptumInsight
      commercial data set from January 2008 to June 2011. The index date was defined as
      the earliest date of prescription for the atypical antipsychotics aripiprazole,
      olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009,
      through June 30, 2010. Medical claims during a 2-year period (12 months before
      and 12 months after the index date) were used to identify relevant diagnostic
      codes from the International Classification of Diseases, Ninth Edition, Clinical
      Modification associated with the antipsychotic prescription. A logistic
      regression analysis was conducted to examine the predictors of use of atypical
      antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or
      major depressive disorder (MDD). RESULTS: Of 18,352 patients included in the
      analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did
      not have an approved diagnosis. Off-label utilization varied, with approximately
      a quarter of patients with prescriptions for quetiapine (24.1%), risperidone
      (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas
      proportions were lower for patients prescribed aripiprazole (14.0%) or
      ziprasidone (13.1%). Of those with a psychiatric disorder other than
      schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions
      were for anxiety disorders, with similar proportions across all atypical
      antipsychotics. Patients were often prescribed quetiapine for substance abuse
      (22.7%), whereas patients with "other psychiatric conditions" were prescribed
      risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis
      indicated that patients prescribed olanzapine, quetiapine, or risperidone were
      significantly more likely to have no diagnostic code for schizophrenia, bipolar
      disorder, or MDD compared with patients prescribed aripiprazole. CONCLUSION:
      Nearly a fifth of commercially insured patients were prescribed atypical
      antipsychotics, in particular, olanzapine, quetiapine, or risperidone, for
      diagnoses that were not aligned with US Food and Drug Administration-approved
      indications.

PMID- 24119768
TI  - DNA gel particles: an overview.
AB  - A general understanding of interactions between DNA and oppositely charged
      compounds forms the basis for developing novel DNA-based materials, including gel
      particles. The association strength, which is altered by varying the chemical
      structure of the cationic cosolute, determines the spatial homogeneity of the
      gelation process, creating DNA reservoir devices and DNA matrix devices that can
      be designed to release either single- (ssDNA) or double-stranded (dsDNA) DNA.
      This review covers recent developments on the topic of DNA gel particles formed
      in water-water emulsion-type interfaces. The degree of DNA entrapment, particle
      morphology, swelling/dissolution behavior and DNA release responses are discussed
      as functions of the nature of the cationic agent used. On the basis of designing
      DNA gel particles for therapeutic purposes, recent studies on the determination
      of the surface hydrophobicity and the hemolytic and the cytotoxic assessments of
      the obtained DNA gel particles have been also reported. 

PMID- 24119770
TI  - Non-human sources of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis is a successful pathogen responsible for the vast
      majority of deadly tuberculosis cases in humans. It rests in a dormant form in
      contaminated people who constitute the reservoir with airborne interhuman
      transmission during pulmonary tuberculosis. M. tuberculosis is therefore regarded
      majoritary as a human pathogen. Here, we review the evidence for anthroponotic M.
      tuberculosis infection in non-human primates, other mammals and psittacines. Some
      infected animals may be sources for zoonotic tuberculosis caused by M.
      tuberculosis, with wild life trade and zoos being amplifying factors. Moreover,
      living animals and cadavers can scatter M. tuberculosis in the environment where
      it could survive for extended periods of time in soil where amoebae could play a
      role. Although marginal in the epidemiology of human tuberculosis, these data
      indicate that M. tuberculosis is not uniquely adapted to humans. 

PMID- 24119769
TI  - Caveolin-1 in renal cell carcinoma promotes tumour cell invasion, and in co
      operation with pERK predicts metastases in patients with clinically confined
      disease.
AB  - BACKGROUND: Up to 40% of patients initially diagnosed with clinically-confined
      renal cell carcinoma (RCC) and who undergo curative surgery will nevertheless
      relapse with metastatic disease (mRCC) associated with poor long term survival.
      The discovery of novel prognostic/predictive biomarkers and drug targets is
      needed and in this context the aim of the current study was to investigate a
      putative caveolin-1/ERK signalling axis in clinically confined RCC, and to
      examine in a panel of RCC cell lines the effects of caveolin-1 (Cav-1) on
      pathological processes (invasion and growth) and select signalling pathways.
      METHODS: Using immunohistochemistry we assessed the expression of both Cav-1 and
      phosphorylated-ERK (pERK) in 176 patients with clinically confined RCC, their
      correlation with histological parameters and their impact upon disease-free
      survival. Using a panel of RCC cell lines we explored the functional effects of
      Cav-1 knockdown upon cell growth, cell invasion and VEGF-A secretion, as well Cav
      1 regulation by cognate cell signalling pathways. RESULTS: We found a significant
      correlation (P = 0.03) between Cav-1 and pERK in a cohort of patients with
      clinically confined disease which represented a prognostic biomarker combination
      (HR = 4.2) that effectively stratified patients into low, intermediate and high
      risk groups with respect to relapse, even if the patients' tumours displayed low
      grade and/or low stage disease. In RCC cell lines Cav-1 knockdown unequivocally
      reduced cell invasive capacity while also displaying both pro-and anti
      proliferative effects; targeted knockdown of Cav-1 also partially suppressed VEGF
      A secretion in VHL-negative RCC cells. The actions of Cav-1 in the RCC cell lines
      appeared independent of both ERK and AKT/mTOR signalling pathways. CONCLUSION:
      The combined expression of Cav-1 and pERK serves as an independent biomarker
      signature with potential merit in RCC surveillance strategies able to predict
      those patients with clinically confined disease who will eventually relapse. In a
      panel of in-vitro RCC cells Cav-1 promotes cell invasion with variable effects on
      cell growth and VEGF-A secretion. Cav-1 has potential as a therapeutic target for
      the prevention and treatment of mRCC.

PMID- 24119771
TI  - Editorial for "non-coding RNA methods".

PMID- 24119772
TI  - Inhaled allergen bronchoprovocation tests.
AB  - The allergen bronchoprovocation test is a long-standing exacerbation model of
      allergic asthma that can induce several clinical and pathophysiologic features of
      asthma in sensitized subjects. Standardized allergen challenge is primarily a
      research tool, and when properly conducted by qualified and experienced
      investigators, it is safe and highly reproducible. In combination with validated
      airway sampling and sensitive detection techniques, allergen challenge allows the
      study of several features of the physiology of mainly TH2 cell-driven asthma in
      relation to the kinetics of the underlying airway pathology occurring during the
      allergen-induced late response. Furthermore, given the small within-subject
      variability in allergen-induced airway responses, allergen challenge offers an
      adequate disease model for the evaluation of new (targeted) controller therapies
      for asthma in a limited number of subjects. In proof-of-efficacy studies thus
      far, allergen challenge showed a fair positive predicted value and an excellent
      negative predictive value for the actual clinical efficacy of new antiasthma
      therapies, underscoring its important role in early drug development. In this
      review we provide recommendations on challenge methods, response measurements,
      sample size, safety, and harmonization for future applications. 

PMID- 24119773
TI  - [Acquired coronary-cameral fistula complicated by a ventricular pseudoaneurysm].
AB  - Coronary-cameral fistulas are usually congenital, rarely acquired; the
      complication of this anomaly with ventricular pseudoaneurysm is exceptional. We
      report a new case of acquired coronary-cameral fistula, occurred in a patient who
      had received a bypass graft and who had suffered from angina 1 year after the
      surgery. On computed tomography coronary angiography, the fistula seems to
      communicate the first diagonal to a left ventricle pseudoaneurysm. Embolization
      of the fistula and filling of the pseudoaneurysm by neurocoil were successfully
      performed. The clinical and angiographic control after 3 months showed symptoms
      improvement and absence of recanalization of the fistula.

PMID- 24119774
TI  - Investigation of the effects of local glutathione and chitosan administration on
      incisional oral mucosal wound healing in rabbits.
AB  - The aim of the present study was to investigate the effects of local glutathione
      (GSH) and chitosan applications on the oxidant events and histological changes
      that occur, during healing processes in rabbits with incisional intraoral mucosal
      wounds. For this purpose, discs containing glutathione and chitosan (1:1) were
      prepared and their physicochemical characteristics were evaluated. New Zealand
      white rabbits were used in in vivo studies. A standard incision was applied to
      the oral mucosa of rabbits. The rabbits were divided into four groups, being: an
      untreated incisional group (n=6), a group treated with discs containing
      GSH+chitosan (n=6), a group treated with discs containing solely chitosan (n=5)
      and a group treated with discs containing solely GSH (n=5). The levels of
      malondialdehyde (MDA), glutathione and nitric oxide (NOx) in the oral wound
      tissues were measured on the fifth day after the injury. Histological changes in
      the wound tissues were also investigated. The tissue MDA levels in the group
      treated with the disc containing GSH+chitosan were found to be lower than those
      in the other groups. There were no statistically significant differences in terms
      of tissue GSH and NOx levels between the group treated with the disc comprising
      GSH+chitosan and the control group that had untreated incision wounds. According
      to the histological findings, wound healing in the group treated with the disc
      containing solely chitosan was found to be better than in the other groups. The
      results of the experiments showed that the local application to the intraoral
      incision wounds of chitosan+GSH, and chitosan alone, can be effective in the
      wound healing processes of soft tissues and dental implants. 

PMID- 24119775
TI  - Functional recovery and rehabilitation of postural impairment and gait ataxia in
      patients with acute cerebellar stroke.
AB  - Studies about recovery from cerebellar stroke are rare. The present study
      assessed motor deficits in the acute phase after isolated cerebellar stroke
      focusing on postural impairment and gait ataxia and outlines the role of lesion
      site on motor outcome, the course of recovery and the effect of treadmill
      training. 23 patients with acute and isolated cerebellar infarction participated.
      Deficits were quantified by ataxia scores and dynamic posturography in the acute
      phase and in a follow up after 2 weeks and 3 months. MRI data were obtained to
      correlate lesion site with motor performance. Half of the patients that gave
      informed consent and walked independently underwent a 2-week treadmill training
      with increasing velocity. In the acute phase patients showed a mild to severe
      ataxia with a worse performance in patients with infarction of the superior in
      comparison to the posterior inferior cerebellar artery. However, after 3 months
      differences between vascular territories were no longer significant. MRI data
      showed that patients with larger infarct volumes had a significantly more severe
      ataxia. In patients with ataxia of stance, gait and lower limbs lesions were more
      common in cerebellar lobules IV to VI. After 3 months a mild ataxia in lower
      limbs and gait, especially in gait speed persisted. Because postural impairment
      had fully recovered, remaining gait ataxia was likely related to incoordination
      of lower limbs. Treadmill training did not show significant effects. Future
      studies are needed to investigate whether intensive coordinative training is of
      benefit in patients with cerebellar stroke. 

PMID- 24119776
TI  - Plantar pressure analysis of accommodative insole in older people with
      metatarsalgia.
AB  - Foot pain frequently reduces physical activity and increases the risk of falls in
      older people. In current orthotic management of forefoot pain, metatarsal padding
      is the main strategy to reduce metatarsal pressure. However, pressure reductions
      are usually diverse and limited. The multi-step accommodative insole is
      fabricated by sequential foam padding on Plastazote under dynamic accommodation
      in daily walking. The aims of this study were to investigate the effectiveness
      and mechanisms of accommodative insole on plantar pressure redistribution in
      older people with metatarsalgia. The study was conducted on 21 old outpatients
      with moderate to severe metatarsalgia, using the ethylene vinyl acetate control,
      9-mm flat Plastazote, and accommodative insoles with and without metatarsal and
      arch support. Outcome measures included pressure-related variables measured by a
      Pedar-X system, and pain scores assessed with a 0-10 Visual Analog Scale. The
      accommodative insole significantly decreased peak pressure under the metatarsal
      heads by 47.2% (p<0.001) and the pain scores from 8.2 to 1.1 (p<0.001). Plantar
      pressure analyses indicated that the effects of dynamic metatarsal contouring and
      cushioning on reducing peak pressure were greater than those of metatarsal
      padding. The temporo-spatial relationships between the toe and metatarsal head
      can assist in explaining an elevated metatarsal pressure and higher risk of falls
      in older people with toe deformities. The multi-step insole is simple in orthotic
      fabrication and ensures an even distribution of plantar pressure loading in
      walking. It can effectively relieve metatarsalgia and help to preserve regular
      walking activity for older people with metatarsalgia. 

PMID- 24119777
TI  - The influence of age, muscle strength and speed of information processing on
      recovery responses to external perturbations in gait.
AB  - Dynamic imbalance caused by external perturbations to gait can successfully be
      counteracted by adequate recovery responses. The current study investigated how
      the recovery response is moderated by age, walking speed, muscle strength and
      speed of information processing. The gait pattern of 50 young and 45 elderly
      subjects was repeatedly perturbed at 20% and 80% of the first half of the swing
      phase using the Timed Rapid impact Perturbation (TRiP) set-up. Recovery responses
      were identified using 2D cameras. Muscular factors (dynamometer) and speed of
      information processing parameters (computer-based reaction time task) were
      determined. The stronger, faster reacting and faster walking young subjects
      recovered more often by an elevating strategy than elderly subjects. Twenty three
      per cent of the differences in recovery responses were explained by a combination
      of walking speed (B=-13.85), reaction time (B=-0.82), maximum extension strength
      (B=0.01) and rate of extension moment development (B=0.19). The recovery response
      that subjects employed when gait was perturbed by the TRiP set-up was modified by
      several factors; the individual contribution of walking speed, muscle strength
      and speed of information processing was small. Insight into remaining modifying
      factors is needed to assist and optimise fall prevention programmes. 

PMID- 24119778
TI  - Motion of the center of mass in children with spastic hemiplegia: balance, energy
      transfer, and work performed by the affected leg vs. the unaffected leg.
AB  - Asymmetry between limbs in people with spastic hemiplegic cerebral palsy (HEMI)
      adversely affects limb coordination and energy generation and consumption. This
      study compared how the affected leg and the unaffected leg of children with HEMI
      would differ based on which leg trails. Full-body gait analysis data and force
      plate data were analyzed for 31 children (11.9 +/- 3.8 years) with HEMI and 23
      children (11.1 +/- 3.1 years) with typical development (TD). Results showed that
      peak posterior center of mass-center of pressure (COM-COP) inclination angles of
      HEMI were smaller than TD when the affected leg trailed but not when the
      unaffected leg trailed. HEMI showed greater peak medial COM-COP inclination
      angles and wider step width than TD, no matter which leg trailed. More
      importantly, when the affected leg of HEMI trailed, it did not perform enough
      positive work during double support to propel COM motion. Consequently, the
      unaffected leg had to perform additional positive work during the early portion
      of single support, which costs more energy. When the unaffected leg trailed, the
      affected leg performed more negative work during double support; therefore, more
      positive work was still needed during early single support, but energy efficiency
      was closer to that of TD. Energy recovery factor was lower when the affected leg
      trailed than when the unaffected leg trailed; both were lower than TD. These
      findings suggest that the trailing leg plays a significant role in propelling COM
      motion during double support, and the 'unaffected' side of HEMI may not be
      completely unaffected. It is important to strengthen both legs.

PMID- 24119779
TI  - Foot roll-over evaluation based on 3D dynamic foot scan.
AB  - Foot roll-over is commonly analyzed to evaluate gait pathologies. The current
      study utilized a dynamic foot scanner (DFS) to analyze foot roll-over. The right
      feet of ten healthy subjects were assessed during gait trials with a DFS system
      integrated into a walkway. A foot sole picture was computed by vertically
      projecting points from the 3D foot shape which were lower than a threshold height
      of 15 mm. A 'height' value of these projected points was determined;
      corresponding to the initial vertical coordinates prior to projection. Similar to
      pedobarographic analysis, the foot sole picture was segmented into anatomical
      regions of interest (ROIs) to process mean height (average of height data by ROI)
      and projected surface (area of the projected foot sole by ROI). Results showed
      that these variables evolved differently to plantar pressure data previously
      reported in the literature, mainly due to the specificity of each physical
      quantity (millimeters vs Pascals). Compared to plantar pressure data arising from
      surface contact by the foot, the current method takes into account the whole
      plantar aspect of the foot, including the parts that do not make contact with the
      support surface. The current approach using height data could contribute to a
      better understanding of specific aspects of foot motion during walking, such as
      plantar arch height and the windlass mechanism. Results of this study show the
      underlying method is reliable. Further investigation is required to validate the
      DFS measurements within a clinical context, prior to implementation into clinical
      practice.

PMID- 24119780
TI  - A crucial role of altered fractional anisotropy in motor problems of very preterm
      children.
AB  - BACKGROUND: Very preterm children (<32 weeks of gestation) are characterized by
      impaired white matter development as measured by fractional anisotropy (FA). This
      study investigates whether altered FA values underpin the widespread motor
      impairments and higher incidence of developmental coordination disorder (DCD) in
      very preterm children at school-age. METHODS: Thirty very preterm born children
      (mean (SD) age of 8.6 (0.3) years) and 47 term born controls (mean [SD] age 8.7
      [0.5] years) participated. Motor development was measured using the Movement
      Assessment Battery for Children. A score below the 15th percentile was used as a
      research diagnosis of DCD. FA values, as measure of white matter abnormalities,
      were determined for 18 major white matter tracts, obtained using probabilistic
      diffusion tensor tractography. RESULTS: Large-sized reductions in FA of the
      cingulum hippocampal tract right (d = 0.75, p = .003) and left (d = 0.76, p =
      .001), corticospinal tract right (d = 0.56, p = .02) and left (d = 0.65, p =
      .009), forceps major (d = 1.04, p < .001) and minor (d = 0.54, p = .02) were
      present in very preterms, in particular with a research diagnosis of DCD. Reduced
      FA values moderately to strongly related to motor impairments. A ROC curve for
      average FA, as calculated from tracts that significantly discriminated between
      very preterm children with and without a research diagnosis of DCD, showed an
      area under curve of 0.87 (95% CI 0.74-1.00, p = .001). CONCLUSIONS: This study
      provides clear evidence that reduced FA values are strongly underpinning motor
      impairment and DCD in very preterm children at school-age. In addition, outcomes
      demonstrate that altered white matter FA values can potentially be used to
      discriminate between very preterm children at risk for motor impairments,
      although future studies are warranted.

PMID- 24119781
TI  - Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann
      Pick C patient.
AB  - Niemann-Pick disease type C is a rare lipid trafficking disorder characterized by
      the accumulation of cholesterol and glycosphingolipids in the brain and viscera.
      Perinatal, early infantile, late infantile, juvenile and adult forms are
      distinguished based on the age of manifestation. In the juvenile form, patients
      in their early years are usually, but not always, symptom free, but present with
      neurodegeneration later in their lives. These include clumsiness, ataxia,
      seizures, motor and intellectual decline. Psychiatric manifestations may occur at
      any stage of the disease. These manifestations include schizophrenia, presenile
      dementia, depression or psychosis. In 2009, miglustat was approved for the
      therapy of the disease. We present a case of a patient with juvenile Niemann-Pick
      C disease whose psychosis was reversed completely by miglustat treatment. Based
      on our clinical experience we suggest considering Niemann-Pick C in cases of
      therapy-resistant psychosis and encourage the introduction of miglustat in
      Niemann-Pick C patients even in the most advanced cases, with respect to
      psychiatric illness.

PMID- 24119782
TI  - Termination-of-resuscitation rule for emergency department physicians treating
      out-of-hospital cardiac arrest patients: an observational cohort study.
AB  - INTRODUCTION: The 2010 cardiopulmonary resuscitation guidelines recommend
      emergency medical services (EMS) personnel consider prehospital termination-of
      resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA) following
      basic life support and/or advanced life support efforts in the field. However,
      the rate of implementation of international TOR rules is still low. Here, we
      aimed to develop and validate a new TOR rule for emergency department physicians
      to replace the international TOR rules for EMS personnel in the field. This rule
      aims to guide physicians in deciding whether to withhold further resuscitation
      attempts or terminate on-going resuscitation immediately after patient arrival.
      METHODS: We analyzed data prospectively collected in a nationwide Utstein-style
      Japanese database between 2005 and 2009, from 495,607 adult patients with OHCA.
      Patients were divided into development (n = 390,577) and validation (n = 105,030)
      groups. The main outcome measures were specificity, positive predictive value
      (PPV), and area under the receiver operating characteristic (ROC) curve for the
      newly developed TOR rule. RESULTS: We developed a new TOR rule that includes 3
      criteria based on the results of multivariate logistic regression analysis for
      predicting a 1-month death after OHCA: no prehospital return of spontaneous
      circulation (adjusted odds ratio [OR], 25.8; 95% confidence interval [CI], 24.7
      26.9), unshockable initial rhythm (adjusted OR, 2.76; 95% CI, 2.54-3.01), and
      unwitnessed by bystanders (adjusted OR, 2.18; 95% CI, 2.09-2.28). The
      specificity, PPV, and area under the ROC curve for this new TOR rule for
      predicting 1-month death in the validation group were 0.903 (95% CI, 0.894
      0.911), 0.993 (95% CI, 0.992-0.993), and 0.874 (95% CI, 0.872-0.876),
      respectively. CONCLUSIONS: We developed and validated a new TOR rule for
      emergency department physicians consisting of 3 prehospital variables (no
      prehospital ROSC, unshockable initial rhythm, and unwitnessed by bystanders) that
      is a >99% predictor of very poor outcome. However, the implementation of this new
      rule in other countries or EMS systems requires further validation studies.

PMID- 24119783
TI  - Cerebral oxygenation in patients undergoing shoulder surgery in beach chair
      position: comparing general to regional anesthesia and the impact on
      neurobehavioral outcome.
AB  - BACKGROUND: Ischemic brain damage has been reported in healthy patients after
      beach chair position for surgery due to cerebral hypoperfusion. Near-infrared
      spectroscopy has been described as a non-invasive, continuous method to monitor
      cerebral oxygen saturation. However, its impact on neurobehavioral outcome
      comparing different anesthesia regimens has been poorly described. METHODS: In
      this prospective, assessor-blinded study, 90 patients undergoing shoulder surgery
      in beach chair position following general (G-group, n=45) or regional anesthesia
      (R-group; n=45) were enrolled to assess the prevalence of cerebral desaturation
      events comparing anesthesia regimens and their impact on neurobehavioral and
      neurological outcome. Anesthesiologists were blinded to regional cerebral oxygen
      saturation values. Baseline data assessed the day before surgery included
      neurological and neurobehavioral tests, which were repeated the day after
      surgery. The baseline data for regional cerebral oxygen saturation/bispectral
      index and invasive blood pressure both at heart and auditory meatus levels were
      taken prior to anesthesia, 5 min after induction of anesthesia, 5 min after beach
      chair positioning, after skin incision and thereafter all 20 min until discharge.
      RESULTS: Patients in the R-group showed significantly less cerebral desaturation
      events (p<0.001), drops in regional cerebral oxygen saturation values (p<0.001),
      significantly better neurobehavioral test results the day after surgery (p<0.001)
      and showed a greater hemodynamic stability in the beach chair position compared
      to patients in the G-group. CONCLUSIONS: The incidence of regional cerebral
      oxygen desaturations seems to influence the neurobehavioral outcome. Regional
      anesthesia offers more stable cardiovascular conditions for shoulder surgery in
      beach chair position influencing neurobehavioral test results at 24h.

PMID- 24119784
TI  - [Endotracheal cuff after multiple injury].

PMID- 24119785
TI  - Association of positive EBAG9 immunoreactivity with unfavorable prognosis in
      breast cancer patients treated with tamoxifen.
AB  - INTRODUCTION: Breast cancer is primarily a hormone-dependent tumor that is
      regulated by the status of the estrogen and progesterone receptors. We previously
      identified EBAG9 as an estrogen-responsive gene in MCF-7 human breast carcinoma
      cells. Upregulation of EBAG9 expression has been observed in several malignant
      tumors such as advanced breast cancers, indicating that EBAG9 might contribute to
      tumor progression. PATIENTS AND METHODS: In the present study, we generated a
      monoclonal antibody against EBAG9, and then performed immunohistochemical
      analysis of EBAG9 expression in specimens obtained from breast cancer patients
      treated with tamoxifen as an adjuvant therapy. RESULTS: EBAG9 immunoreactivity
      was detected in the cytoplasm of breast cancer cells and was significantly
      elevated in breast cancer samples from patients who relapsed during or after
      adjuvant tamoxifen treatment. Positive EBAG9 immunoreactivity was significantly
      correlated with poor patient prognosis. CONCLUSION: These results suggest that
      EBAG9 expression in tumor regions is associated with an unfavorable prognosis in
      breast cancer patients treated with tamoxifen.

PMID- 24119787
TI  - Surgical and oncological outcome after skin-sparing mastectomy and immediate
      breast reconstruction.
AB  - INTRODUCTION: We present clinical outcomes after SSM in operable breast cancer
      especially in light of increased diagnoses of in situ disease after screening and
      increased usage of adjuvant aromatase inhibitors (AIs) in recent years. PATIENTS
      AND METHODS: Case records of 81 patients who had SSM for cancer over 4 years
      (April 2006-July 2010) were reviewed. RESULTS: Eighty-one patients (median age,
      51.7 years; range, 31.5-66.1 years) had 82 SSMs with immediate breast
      reconstruction (IBR) (59 implant-based; 23 latissimus dorsi flap). Median tumor
      size was 22 mm (range, 1-86 mm) including in situ disease, and tumor types were
      invasive (n = 48) and noninvasive (n = 34). Median clearance margin was 5 mm
      (range, 0-45 mm). Sentinel node was positive in 15 SSM (19.5%) excluding 5 in
      pure in situ disease. Median Nottingham prognostic index was 3.54 (range, 2.1
      6.98), 84% were estrogen receptor-positive (pure in situ, 70.6%), and 8.5% were
      HER2-positive. Radiotherapy to breast was given to 17.1% of patients and 37.8% of
      patients received hormone therapy (tamoxifen, 24.4%; upfront AI, 4.9%; switch
      regime, 8.5% [ie, tamoxifen to exemestane at 2 years). Eight patients (9.6%) had
      infection/wound healing problems with loss of implant in 3 (3.6%). At median
      follow-up of 23.9 months (range, 9-64), there was 1 local with systemic (liver)
      and 1 SR only (brain and liver) after invasive disease with median disease-free
      survival of 24.4 months (range, 6.1-61.9). CONCLUSIONS: Despite less use of AIs
      in our series, the local recurrence (2%) and SR (4%) rates were less than
      reported in the literature for invasive tumors. This suggests that SSM provides
      opportunity for enhanced esthetic outcome with IBR without compromise of the
      local oncological safety compared with conventional simple mastectomy.

PMID- 24119786
TI  - Benign papillomas without atypia diagnosed on core needle biopsy: experience from
      a single institution and proposed criteria for excision.
AB  - BACKGROUND: The management of benign papilloma (BP) without atypia identified on
      breast core needle biopsy (CNB) is controversial. In this study, we determined
      the upgrade rate to malignancy for BPs without atypia diagnosed on CNB and
      whether there are factors associated with upgrade. METHODS: Through our pathology
      database search, we studied 80 BPs without atypia identified on CNB from 80
      patients from 1997 to 2010, including 30 lesions that had undergone excision and
      50 lesions that had undergone >= 2 years of radiologic follow-up. Associations
      between surgery or upgrade to malignancy and clinical, radiologic, and pathologic
      features were analyzed. RESULTS: Mass lesions, lesions sampled by ultrasound
      guided CNB, and palpable lesions were associated with surgical excision. All 3
      upgraded cases were mass lesions sampled by ultrasound-guided CNB. None of the
      lesions with radiologic follow-up only were upgraded to malignancy. The overall
      upgrade rate was 3.8%. None of the clinical, radiologic, or histologic features
      were predictive of upgrade. CONCLUSION: Because the majority of patients can be
      safely managed with radiologic surveillance, a selective approach for surgical
      excision is recommended. Our proposed criteria for excision include
      pathologic/radiologic discordance or sampling by ultrasound-guided CNB without
      vacuum assistance when the patient is symptomatic or lesion size is >= 1.5 cm.

PMID- 24119788
TI  - MT1-MMP in breast cancer: induction of VEGF-C correlates with metastasis and poor
      prognosis.
AB  - BACKGROUND: Recent evidence suggests that vascular endothelial growth factor-C
      (VEGF-C)- dependent tumour production promotes lymphangiogenesis, while membrane
      type matrix 1 metalloproteinase (MT1-MMP) is involved in the critical steps
      leading to carcinogenesis. However, the role of MT1-MMP in lymphangiogenesis and
      lymphatic metastasis remains poorly understood. In the present study, we
      investigated the relationship between MT1-MMP and VEGF-C in human breast cancer
      and correlated MT1-MMP and VEGF-C expression with lymphangiogenesis and
      prognosis. METHODS: MT1-MMP and VEGF-C levels were compared in five breast
      carcinoma cell lines. We used a membrane invasion assay to assess the effect of
      MT1-MMP and VEGF-C expression, as well as anti-MT1-MMP and VEGF-C antibodies, on
      cancer cell invasion. We further assessed MT1-MMP and VEGF-C immunoreactivity and
      lymph vessels in a cohort of human breast cancer specimens (n = 106) and
      associated MT1-MMP and VEGF-C expression with clinicopathological parameters,
      such as lymphatic vessel density (LVD), and patient prognosis. RESULTS: MT1-MMP
      and VEGF-C expression differed among the five breast cancer cell lines and MT1
      MMP and VEGF-C expression were correlated with tumour cell invasion. VEGF-C mRNA
      expression levels and invasive activity of MDA-MB-231 cells was inhibited by an
      anti-MT1-MMP antibody in a concentration-dependent manner. A significant
      correlation was found between the expression of MT1-MMP and VEGF-C in breast
      cancer patient samples and elevated MT1-MMP and VEGF-C expression was associated
      with higher LVD, lymph node metastasis, cancer stage, and a decline in overall
      survival rates. CONCLUSIONS: Our data demonstrate that MT1-MMP expression is
      closely correlated with VEGF-C expression, and that MT1-MMP promotes
      lymphangiogenesis by up-regulating VEGF-C expression in human breast cancer.
      Thus, elevated MT1-MMP may serve as a significant prognostic factor in breast
      cancer.

PMID- 24119789
TI  - [A poorly known cause of peripartum hemorrhage].

PMID- 24119790
TI  - Colloids vs crystalloids for stroke volume optimization: The colloids are taking
      on water.

PMID- 24119791
TI  - Impaired musical ability in people with schizophrenia.
AB  - BACKGROUND: Assessment of the musical ability of people with schizophrenia has
      attracted little interest despite the diverse and substantive findings of
      impairments in sound perception and processing and the therapeutic effect of
      music in people with the illness. The present study investigated the musical
      ability of people with schizophrenia and the association with psychiatric
      symptoms and cognition. METHODS: We recruited patients with chronic schizophrenia
      and healthy controls for participation in our study. To measure musical ability
      and cognitive function, we used the Montreal Battery of Evaluation of Amusia
      (MBEA) and the Brief Assessment of Cognition in Schizophrenia (BACS). We carried
      out a mediation analysis to investigate a possible pathway to a deficit in
      musical ability. RESULTS: We enrolled 50 patients and 58 controls in the study.
      The MBEA global score in patients with schizophrenia was significantly lower than
      that in controls (p < 0.001), and was strongly associated with both the composite
      cognitive function score (r = 0.645, p < 0.001) and the negative symptom score (r
      = -0.504, p < 0.001). Further analyses revealed direct and indirect effects of
      negative symptoms on musical ability. The indirect effects were mediated through
      cognitive impairment. LIMITATIONS: The relatively small sample size did not
      permit full evaluation of the possible effects of age, sex, education, medication
      and cultural influences on the results. CONCLUSION: Examining the associations
      between musical deficits, negative symptoms and cognitive imapirment in patients
      with schizophrenia may identify shared biological mechanisms.

PMID- 24119792
TI  - Neural correlates of recognition memory of social information in people with
      schizophrenia.
AB  - BACKGROUND: Social dysfunction is a hallmark characteristic of schizophrenia.
      Part of it may stem from an inability to efficiently encode social information
      into memory and retrieve it later. This study focused on whether patients with
      schizophrenia show a memory boost for socially relevant information and engage
      the same neural network as controls when processing social stimuli that were
      previously encoded into memory. METHODS: Patients with schizophrenia and healthy
      controls performed a social and nonsocial picture recognition memory task while
      being scanned. We calculated memory performance using d'. Our main analysis
      focused on brain activity associated with recognition memory of social and
      nonsocial pictures. RESULTS: Our study included 28 patients with schizophrenia
      and 26 controls. Healthy controls demonstrated a memory boost for socially
      relevant information. In contrast, patients with schizophrenia failed to show
      enhanced recognition sensitivity for social pictures. At the neural level,
      patients did not engage the dorsomedial prefrontal cortex (DMPFC) as much as
      controls while recognizing social pictures. LIMITATIONS: Our study did not
      include direct measures of self-referential processing. All but 3 patients were
      taking antipsychotic medications, which may have altered both the behavioural
      performance during the picture recognition memory task and brain activity.
      CONCLUSION: Impaired social memory in patients with schizophrenia may be
      associated with altered DMPFC activity. A reduction of DMPFC activity may reflect
      less involvement of self-referential processes during memory retrieval. Our
      functional MRI results contribute to a better mapping of the neural disturbances
      associated with social memory impairment in patients with schizophrenia and may
      facilitate the development of innovative treatments, such as transcranial
      magnetic stimulation.

PMID- 24119793
TI  - Impaired frontothalamic circuitry in suicidal patients with depression revealed
      by diffusion tensor imaging at 3.0 T.
AB  - BACKGROUND: The neurobiology of suicide is largely unknown. Studies of white
      matter tracts in patients with a history of suicidal behaviour have shown
      alteration in the left anterior limb of the internal capsule (ALIC). Our aim was
      to determine whether particular target fields of fibre projections through the
      ALIC are affected in depressed patients who recently attempted suicide. METHODS:
      We studied patients with major depressive disorder (MDD) with and without a
      history of suicide attempts and healthy controls using diffusion tensor imaging
      (DTI) and deterministic tractography to generate fibre tract maps for each
      participant. Tract voxels were coded as being unique to the left ALIC. We
      compared the mean percentage of fibres projecting to relevant brain regions in
      the 3 groups using analysis of covariance. RESULTS: We included 63 patients with
      MDD (23 with and 40 without a history of suicide attempts) and 46 controls in our
      study. Both groups of depressed patients had reduced fibre projections through
      the ALIC to the left medial frontal cortex, orbitofrontal cortex and thalamus.
      Those with a history of suicide attempts had greater abnormalities than those
      without suicide attempts in the left orbitofrontal cortex and thalamus.
      LIMITATIONS: Diffusion tensor imaging deterministic tracking is unable to
      distinguish between afferent and efferent pathways, limiting our ability to
      distinguish the directionality of altered fibre tracts. CONCLUSION:
      Frontothalamic loops passing through the ALIC are abnormal in patients with
      depression and significantly more abnormal in depressed patients with a history
      of suicide attempts than in those without a history of suicide attempts. Abnormal
      projections to the orbitofrontal cortex and thalamus may disrupt affective and
      cognitive functions to confer a heightened vulnerability for suicidal behaviour.

PMID- 24119794
TI  - Short communication: Dairy bedding type affects survival of Prototheca in vitro.
AB  - Protothecae are algal pathogens, capable of causing bovine mastitis, that are
      unresponsive to treatment; they are believed to have an environmental reservoir.
      The role of bedding management in control of protothecal mastitis has not been
      studied. The purpose of this study was to evaluate the growth of either
      environmental or mastitis-associated Prototheca genotypes in dairy bedding
      materials that are commonly used in Maine. Prototheca zopfii genotypes 1 and 2
      (gt1 and gt2) were inoculated into sterile broth only (control ), kiln-dried
      spruce shavings, "green" hemlock sawdust, sand, or processed manure-pack beddings
      with broth, and incubated for 2 d. Fifty microliters of each isolate was then
      cultured onto plates and the resulting colonies counted at 24 and 48 h
      postinoculation. Shavings were associated with significantly less total
      Prototheca growth than other bedding types. Growth of P. zopfii gt1 was
      significantly higher than that of gt2 in the manure-pack bedding material. Spruce
      shavings, compared with manure, sand, or sawdust, may be a good bedding type to
      prevent growth of Prototheca. Based on these in vitro findings, bedding type may
      affect Prototheca infection of cattle in vivo.

PMID- 24119796
TI  - Expression of key lipid metabolism genes in adipose tissue is not altered by once
      daily milking during a feed restriction of grazing dairy cows.
AB  - The objective of this study was to investigate the effect of reduced milking
      frequency, at 2 feeding levels, on gene expression in adipose tissue of grazing
      dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein
      Friesian * Jersey cows (n=120) were grazed on pasture and milked twice daily (2*)
      from calving to 34+/-6d in milk (mean +/- standard deviation). Cows were then
      allocated to 1 of 4 treatments in a 2*2 factorial arrangement. Treatments
      consisted of 2 milking frequencies (2* or once daily; 1*) and 2 feeding levels
      for 3 wk: adequately fed (AF), consuming 14.3 kg of dry matter/cow per day, or
      underfed (UF), consuming 8.3 kg of dry matter/cow per day. After the treatment
      period, all cows were fed to target grazing residuals >=1,600 kg of DM/cow per
      day and milked 2* for 20 wk. Adipose tissue was collected from 12 cows per
      treatment by subcutaneous biopsy at -1, 3, and 5 wk relative to treatment start,
      RNA was extracted, and transcript abundance of genes involved in lipid metabolism
      was quantified using a linear mixed model. At the end of the 3-wk treatment
      period, transcript abundance of genes involved in fatty acid (FA) uptake into
      adipose tissue (LPL), FA synthesis [FA synthase (FASN) and stearoyl-coenzyme A
      desaturase (SCD)], FA oxidation [acyl-coenzyme A synthetase long-chain family
      member 1 (ACSL1) and carnitine palmitoyltransferase 2 (CPT2)], glyceroneogenesis
      [glycerol-3-phosphate dehydrogenase 1 (GPD1) and pyruvate carboxylase (PC)], and
      triacylglyceride synthesis [diacylglycerol O-acyltransferase 2 (DGAT2)] were
      greater in AF1* cows compared with all other treatments. However, when cows were
      underfed, no effects of milking frequency were observed on transcript abundance
      of genes involved in adipose lipid metabolism. Despite increases in plasma NEFA
      concentrations in UF cows, no effects of underfeeding were observed on the
      transcription of lipolytic genes. At 5 wk, after cows were returned to 2* milking
      and standard feed allowance, transcript abundances of genes involved in FA
      synthesis [acetyl-coenzyme A carboxylase alpha (ACACA) and SCD)] were increased
      in cows previously UF. Expression of ACSL1 was decreased in UF1* cows relative to
      UF2* cows and CPT2 expression was greater in AF1* cows compared with AF2* cows.
      In conclusion, after 3 wk of reduced milking frequency during a feed restriction,
      transcription of genes involved in lipid metabolism in adipose tissue were not
      altered, possibly due to the reduced milk production in these animals. However, 3
      wk of 1* milking in AF cows increased transcription of genes involved in FA
      synthesis, oxidation, and triacylglyceride synthesis.

PMID- 24119795
TI  - Characterization of clinical mastitis occurring in cows on 50 large dairy herds
      in Wisconsin.
AB  - In recent years, the US dairy industry has experienced significant demographic
      changes, with an increase in the number of large herds. The objectives of the
      present study were to characterize clinical mastitis occurring in cows on large
      dairy herds in Wisconsin. Participating herds (n=50) were required to have a
      minimum of 200 lactating animals, participate in monthly DHI testing (including
      monthly individual cow somatic cell count), use computerized herd records, use a
      milking routine that included fore-stripping quarters for detection of mastitis,
      and use antimicrobials to treat affected cows. After study personnel visited the
      farm, each herd was instructed to enroll the next 17 cows that experienced
      clinical mastitis, regardless of severity. At detection of clinical mastitis and
      14 to 21 d after treatment ended, duplicate quarter milk samples were collected
      from all affected quarters and used for microbiological analysis. Treatments of
      affected cows were performed according to existing individual farm protocols. Cow
      level follow-up data was collected for 90 d after enrollment. Microbiological
      diagnoses at enrollment included gram-negative (35.6%), no growth (27.3%), gram
      positive (27.5%), and other (9.6%). Of the 741 cases, the most prevalent
      pathogens were Escherichia coli (22.5%), followed by environmental streptococci
      (12.8%), Klebsiella spp. (6.9%), and coagulase-negative staphylococci (6.1%).
      Bacteriological cure was 75.0% for cases caused by gram-negative pathogens
      (n=136), 50.8% for cases caused by gram-positive pathogens (n=128), 47.5% for
      cases caused by other pathogens (n=40), and 73.2% for cases which did not result
      in microbial growth (n=123). Of the 583 cases with severity recorded, the
      distribution of mild, moderate, and severe symptoms was 47.8, 36.9, and 15.3%,
      respectively. The majority of cases presenting with severe symptoms were caused
      by gram-negative pathogens. Treatment cure was greater for gram-negative
      pathogens and cases for which no pathogens were recovered as compared with cases
      caused by other etiologies. Cows experiencing severe cases were more likely to
      receive multiple antimicrobial treatments.

PMID- 24119797
TI  - Performance and health responses of dairy calves offered different milk replacer
      allowances.
AB  - Eighty female Holstein calves (12+/-4.1 d of age and 42+/-4.3 kg of BW) were
      collected from different herds, brought to the study site, and blocked by age and
      assigned to either a 6 L/d maximum daily milk replacer (MR) allowance (LMR) or a
      maximum MR allowance of 8 L/d (HMR). Calves were kept in individual hutches until
      52 d of age and then moved into pens, forming groups of 10. All calves had ad
      libitum access to a mash starter feed. Calves in both treatments received the MR
      distributed in 3 separate allotments between 1 wk after the beginning of the
      study and 52 d of age. Then, all calves were moved to group pens and preweaned by
      offering 2 L/calf of the same MR twice daily in a trough until the age of 59 d,
      when MR offer was further reduced to a single dose of 2 L until the age of 73 d,
      when all calves were completely weaned. Individual starter feed and MR
      consumption was recorded on a daily basis until 52 d of age, and on a group basis
      until weaning time. Body weight was measured at the beginning of the study and at
      52 (preweaning), 73 (weaning), and 110, 160, and 228 d of age. Solid feed
      consumption (mean +/- SE) was greater in LMR (821+/-42.1 g/d) than in HMR calves
      (462+/-42.1 g/d) between 42 d of age and 52 d (preweaning). As expected, as age
      increased, solid feed consumption increased, and LMR showed a more marked
      increase than HMR calves. Despite the greater solid feed intake of LMR calves,
      HMR grew faster than LMR calves until preweaning time, but from preweaning to
      weaning, LMR calves grew more than HMR calves (977 vs. 857+/-30.7 g/d,
      respectively; mean +/- SE). No differences in feed efficiency were observed.
      While calves were individually housed, no differences were observed in the
      incidence of bovine respiratory disease or diarrhea between treatment groups. We
      concluded that, under the milk regimen, age range of calves, and weaning method
      used in the current study, before preweaning, HMR calves grow more than LMR
      calves, but between preweaning and weaning, LMR grow more than HMR calves,
      overcoming the difference in BW at preweaning. As a result, with the weaning
      scheme followed herein, providing more milk does not ensure greater performance;
      no differences are obtained in BW at weaning and at 228 d of life. Also, based on
      solid feed consumption patterns seen in this study, we determined that the
      optimum age to reduce MR allowances and foster solid feed intake is around 45 d
      of age.

PMID- 24119799
TI  - Reproductive performance of dairy farms in western Buenos Aires province,
      Argentina.
AB  - The objective of this study was to describe the reproductive performance of 23
      grazing-based dairy farms from western Buenos Aires province in Argentina. The
      data set included data from the breeding season starting in May 2011 and ending
      in March 2012. Submission, conception, and pregnancy rates ranged from 42.4 to
      70.2%, 20.1 to 44.9%, and 10.3 to 24.5%, respectively. No correlation was
      observed between conception and submission rates, suggesting that dairy farms
      with poor submission rates but with relatively high conception rates might
      increase pregnancy rates by simply putting more effort into increasing estrus
      detection and submission rates. Decreases in submission and conception rates were
      observed among 21-d cycles, indicating seasonal variation. A greater number of
      cows in estrus at the beginning of the breeding period could have facilitated
      estrus detection and therefore increased submission rates. In addition,
      restarting the breeding activities with timed artificial insemination programs
      may explain the highest submission rates at the beginning of the breeding period.
      A first decrease of 5.1 percentage units in conception rate was observed during
      the spring (October-November) and an additional decrease of 2.4 percentage units
      in conception rate was observed during the summer (January-February). Decreases
      in conception rates could be related to high intakes of high-protein diets, heat
      stress, or a combination of both. Attenuating heat stress during the summer may
      be critical for maximizing conception rates in grazing systems from western
      Buenos Aires province. 

PMID- 24119798
TI  - Use of PCR-restriction fragment length polymorphism analysis for identification
      of yeast species isolated from bovine intramammary infection.
AB  - This study reports a rapid PCR-based technique using a one-enzyme RFLP for
      discrimination of yeasts isolated from bovine clinical and subclinical mastitis
      milk samples. We analyzed a total of 1,486 milk samples collected over 1 yr in
      south Sardinia and northern Italy, and 142 yeast strains were preliminarily
      grouped based on their cultural morphology and physiological characteristics.
      Assimilation tests were conducted using the identification kit API ID 32C and
      APILAB Plus software (bioMerieux, Marcy l'Etoile, France). For PCR-RFLP analysis,
      the 18S-ITS1-5.8S ribosomal(r)DNA region was amplified and then digested with
      HaeIII, and dendrogram analysis of RFLP fragments was carried out. Furthermore,
      within each of the groups identified by the API or PCR-RFLP methods, the
      identification of isolates was confirmed by sequencing of the D1/D2 region using
      an ABI Prism 310 automatic sequencer (Applied Biosystems, Foster City, CA). The
      combined phenotypic and molecular approach enabled the identification of 17 yeast
      species belonging to the genera Candida (47.9%), Cryptococcus (21.1%),
      Trichosporon (19.7%), Geotrichum (7.1%), and Rhodotorula (4.2%). All Candida
      species were correctly identified by the API test and their identification
      confirmed by sequencing. All strains identified with the API system as Geotrichum
      candidum, Cryptococcus uniguttulatus, and Rhodotorula glutinis also produced
      characteristic restriction patterns and were confirmed as Galactomyces geotrichum
      (a teleomorph of G. candidum), Filobasidium uniguttulatum (teleomorph of Crypt.
      uniguttulatus), and R. glutinis, respectively, by D1/D2 rDNA sequencing. With
      regard to the genus Trichosporon, preliminary identification by API was
      problematic, whereas the RFLP technique used in this study gave characteristic
      restriction profiles for each species. Moreover, sequencing of the D1/D2 region
      allowed not only successful identification of Trichosporon gracile where API
      could not, but also correct identification of misidentified isolates. In
      conclusion, the 18S-ITS1-5.8S region appears to be useful in detecting genetic
      variability among yeast species, which is valuable for taxonomic purposes and for
      species identification. We have established an RFLP database for yeast species
      identified in milk samples using the software GelCompar II and the RFLP database
      constitutes an initial method for veterinary yeast identification. 

PMID- 24119800
TI  - The effect of prepartum intravaginal bacteriophage administration on the
      incidence of retained placenta and metritis.
AB  - The objective of this study was to evaluate the effect of prepartum intravaginal
      administration of an anti-Escherichia coli bacteriophage cocktail on uterine
      health and reproductive performance of lactating dairy cows. The study was
      conducted on a commercial dairy farm located near Ithaca, New York, from March to
      September 2012, and 107 cows were enrolled. The cows were divided randomly into 2
      groups (treatment and control); treatment group cows were submitted to 3
      intravaginal administrations of 20 mL of a bacteriophage cocktail including 10
      different phages in a lysate with titration of approximately 10(9) plaque-forming
      units, on d 230, 260, and 275 of gestation. Control cows were not treated with a
      placebo, and physical examination and sample collection was conducted equally for
      both groups. Vaginal swabs were collected at d 230, 260, and 275 d of gestation,
      cervical swabs were collected at 3+/-1 d in milk, and blood was collected at 275
      d of gestation for nonesterified fatty acids and interleukin (IL)-6 serum level
      measurements and at 10 DIM for beta-hydroxybutyrate and IL-6 serum level
      measurements. The bacteriophage cocktail significantly increased the incidence of
      retained placenta and metritis. Swab samples were cultured for E. coli and no
      difference was found between treatment and control groups. The lysate contained
      6*10(9) IU of lipopolysaccharide/mL and could have caused prepartum
      overstimulation of toll-like receptor-4 (TLR4)-chemokine pathway, leading to a
      weaker immune response. However, IL-6 was not affected by treatment, although
      sample size was insufficient to prove a treatment effect on the suppression of
      the chemokine cascade and innate immune system. Bacteriophage treatment had an
      excellent bactericidal effect in previous in vitro trials; however, special
      attention must be given to production of the cocktail to obtain a purified
      solution free of E. coli bacterial products and fragments, particularly
      lipopolysaccharide.

PMID- 24119801
TI  - Effects of grain, fructose, and histidine feeding on endotoxin and oxidative
      stress measures in dairy heifers.
AB  - Ruminal endotoxin and plasma oxidative stress biomarker concentrations were
      studied in dairy heifers challenged with grain, fructose, and histidine in a
      partial factorial study. Holstein-Friesian heifers [n=30; average body weight
      (BW) of 359.3+/-47.3 kg] were randomly allocated to 5 treatment groups: (1)
      control (no grain); (2) grain [crushed triticale at 1.2% of BW dry matter intake
      (DMI)]; (3) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI); (4) grain (1.2%
      of BW DMI) + histidine (6g/head); and (5) grain (0.8% of BW DMI) + fructose (0.4%
      of BW DMI) + histidine (6 g/head). Rumen samples were collected by stomach tube
      5, 65, 115, 165, and 215 min after diet consumption and blood samples at 5 and
      215 min after consumption. Rumen fluid was analyzed for endotoxin concentrations.
      Plasma was analyzed for concentrations of the following oxidative stress
      biomarkers: reactive oxygen metabolites (dROM), biological antioxidant potential
      (BAP), advanced oxidation protein products, and ceruloplasmin, and activity of
      glutathione peroxidase. Dietary treatment had no effect on concentrations of
      endotoxin or oxidative stress biomarkers. We observed no interactions of
      treatment by time. Ruminal concentrations of endotoxin decreased during the
      sampling period from 1.12*10(5) +/- 0.06 to 0.92*10(5) endotoxin units/mL +/-
      0.05 (5 and 215 min after diet consumption, respectively). Concentrations of dROM
      and the oxidative stress index (dROM/BAP * 100) increased over the sampling
      period, from 108.7 to 123.5 Carratelli units (Carr U), and from 4.1 to 4.8,
      respectively. Ceruloplasmin concentrations markedly declined 5 min after the
      consumption of diets, from 190 to 90 mg/L over the 215-min sampling period.
      Overall, a single feeding challenge for dairy cattle with grain, fructose, and
      histidine, and combinations thereof, may not be sufficient to induce marked
      changes in endotoxin or oxidative stress biomarker concentrations.

PMID- 24119802
TI  - Expression of adipokine and lipid metabolism genes in adipose tissue of dairy
      cows differing in a female fertility quantitative trait locus.
AB  - We have previously characterized 2 haplotypes (Fertil+ and Fertil-) of Holstein
      dairy cows differing in 1 female fertility quantitative trait locus (QTL) located
      on chromosome 3 (QTL-Fert-F-BTA3) between positions 9.8 and 13.5 cM. This QTL is
      composed of 124 genes, some of them being involved in metabolism or reproduction.
      Primiparous Fertil+ and Fertil- cows exhibited 69 and 39% pregnancy rate at first
      service, respectively. A difference in plasma nonesterified fatty acid
      concentrations observed between both haplotypes might indicate a difference in
      adipose tissue mobilization. We compared adipose tissue gene expression in
      Fertil+ and Fertil- cows during their second lactation, at 2 physiological
      stages, implying either intense lipid mobilization (1 wk postpartum) or fat
      storage (5 mo of gestation). We investigated by reverse-transcription
      quantitative PCR the mRNA gene expression of 5 positional candidate genes located
      in the QTL-Fert-F-BTA3, as well as 18 other functional candidate genes encoding
      proteins involved in lipid metabolism and several adipokines. Among them, genes
      involved in either lipolysis or lipogenesis were chosen as controls because they
      were previously described in dairy cow adipose tissue. A hierarchical clustering
      was performed to group genes according to their expression pattern, allowing 2
      clusters to be determined. Cluster 1 was composed of genes that were
      overexpressed during mobilization (ADIPOQ, ADIPOR2, LIPE, FABP4, PLIN1, RARRES,
      LEPR, and CPT1A) and cluster 2 of genes overexpressed during reconstitution of
      body reserves (ACACA, FASN, and SCD). Genes belonging to cluster 1 (LIPE, FABP4,
      PLIN1, and CPT1A) are known to be involved in lipolysis and fatty acid oxidation,
      and genes belonging to cluster 2 (ACACA, FASN, and SCD) are known to be involved
      in fatty acid synthesis. The expression of 5 genes from cluster 1 was correlated
      to plasma nonesterified fatty acid levels and thus to mobilization of body
      reserves in dairy cows (ADIPOQ, ADIPOR2, LIPE, PLIN1, and FABP4). During the
      mobilization stage, none of the positional candidate genes belonging to QTL-Fert
      F-BTA3 (ADAR, MTX1, SHC1, SPTA1, and PAQR6) showed a difference in expression
      between the 2 haplotypes. Interestingly, ADIPOQ and ADIPOR2 were the only genes
      showing a significant mRNA overexpression in Fertil- cows at the mobilization
      stage. Further studies focusing on plasma adiponectin level and adipokine actions
      on the ovary are needed to investigate its potential role in dairy cow fertility.

PMID- 24119803
TI  - Short communication: Feeding linseed oil to dairy goats with competent reticular
      groove reflex greatly increases n-3 fatty acids in milk fat.
AB  - A crossover experiment was designed to compare the effects of 2 ways of feeding
      linseed oil on milk fat fatty acid (FA) composition. Ten lactating goats, trained
      to keep competent their inborn reticular groove reflex, received a daily dose of
      linseed oil (38 g/d) either with their solid (concentrate) feed (CON) or
      emulsified in skim milk and bottle-fed (BOT). Two groups of 5 goats received
      alternative and successively each of the treatments in two 15-d periods. alpha
      Linolenic acid in milk fat rose up to 13.7% in the BOT versus 1.34% in the CON
      treatment. The n-6 to n-3 FA ratio was significantly reduced in goats receiving
      bottle-fed linseed oil (1.49 vs. 0.49). Contents of rumen biohydrogenation
      intermediates of dietary unsaturated FA were high in milk fat of goats under the
      CON treatment but low in those in the BOT treatment. These results point to a
      clear rumen bypass of the bottle-fed linseed oil. This strategy allows obtaining
      milk fat naturally very rich in n-3 FA and very low in trans FA. Translating this
      approach into practical farm conditions could enable farmers to produce milk
      enriched in specific FA.

PMID- 24119804
TI  - A new magnetic resonance imaging approach for discriminating Sardinian sheep milk
      cheese made from heat-treated or raw milk.
AB  - The evaluation of milk heat treatment on dairy products via reliable analytical
      methods is a challenging issue that involves both industrial and fundamental
      research. We describe a new magnetic resonance imaging (MRI) protocol for
      discriminating Sardinian sheep milk cheese originating from heat-treated or raw
      milk. Thirty-six samples (18 pecorino cheeses manufactured from heat-treated milk
      and 18 Fiore Sardo cheeses made from raw milk) were investigated by means of MRI
      and bi-exponential signal decay analysis. The protocol is capable of discerning
      cheeses by virtue of the different distribution of the transversal (T2)
      relaxation time constant. Cheeses from heat-treated milk showed a significantly
      higher area fraction (~70-80%), corresponding to the fast relaxing water protons
      (T2 ~ 9 ms), compared with raw milk cheeses, whereas the opposite was observed
      for the long T2 (T2 ~ 35 ms) proton population. The MRI protocol described is
      rapid and nondestructive, and it provides statistically significant
      discrimination between ewe milk cheeses made from heat-treated and raw milk.

PMID- 24119805
TI  - Quantification of milk yield and composition changes as affected by subclinical
      mastitis during the current lactation in sheep.
AB  - The aim of this work was to quantify, on a half-udder basis, the changes in ewe
      milk yield and composition caused by unilateral subclinical mastitis within the
      current lactation. Fluctuations due to production level, infection severity, time
      from the onset of infection, and lactation curves were also studied. Yield and
      composition of milk from half-udders of unilateral infected ewes were compared
      between them and with a set of healthy halves using a mixed model. The experiment
      was completed with a whole-udder approach on the same animals. To test the effect
      of intramammary infection (IMI) in the 7 wk following the onset of infection, 20
      ewes that acquired unilateral subclinical mastitis during lactation and 40
      healthy ewes were used. Another group of 20 unilaterally infected ewes from wk 1
      of lactation and other 40 healthy ewes were studied to test the effect of IMI on
      lactational milk yield and composition. The individual milk loss in ewes infected
      during lactation was 15% for the 7 wk following the onset of infection, and 6.6%
      more milk was produced by the uninfected half to compensate milk lost by the
      infected half. Lactational milk yield loss in ewes infected from wk 1 postpartum
      was 17%. The changes in milk yield were noticed from the week of infection
      diagnosis. The production level of animals influenced the milk yield changes
      caused by IMI in such a way that the more productive ewes lost more milk,
      although these losses were proportional to their production level. On the other
      hand, infection severity affected milk loss between glands, being more pronounced
      as somatic cell count increased. A clear decrease of lactose content and
      casein:protein ratio due to subclinical IMI was observed and it remained
      throughout the postinfection period. Improving udder health status is necessary
      to maintain milk production and quality in dairy ewes during lactation.

PMID- 24119806
TI  - Passage of stable isotope-labeled grass silage fiber and fiber-bound protein
      through the gastrointestinal tract of dairy cows.
AB  - Fractional passage rates are required to predict nutrient absorption in ruminants
      but data on nutrient-specific passage kinetics are largely lacking. With the use
      of the stable isotope ratio (delta) as an internal marker, we assessed passage
      kinetics of fiber and fiber-bound nitrogen (N) of intrinsically labeled grass
      silage from fecal and omasal excretion patterns of delta(13)C and delta(15)N. In
      a 6*6 Latin square, lactating dairy cows received grass silages [455 g/kg of
      total diet dry matter (DM) ] in a 2*3 factorial arrangement from ryegrass swards
      fertilized at low (45 kg of N/ha) or high (90 kg of N/ha) levels of N and
      harvested at 3 maturity stages. Feed intake (16.7+/-0.48 kg of DM/d; mean +/-
      standard error of the mean) and milk yield (26.7+/-0.92 kg/d) increased at the
      high level of N fertilization and at decreasing maturity. Nutrient digestibility
      decreased with increasing plant maturity, particularly at the high level of N
      fertilization, essentially reflecting dietary treatment effects on the
      nutritional composition of the grass silage. Fractional rumen passage rates (K1)
      were highest and total mean retention time in the gastrointestinal tract (TMRT)
      was lowest when based on the external marker chromium mordanted fiber (Cr-NDF;
      0.047/h and 38.0 h, respectively). Fecal delta(13)C in the acid detergent fiber
      fraction ((13)CADF) provided the lowest K1 (0.023/h) and the highest TMRT (61.1
      h) and highest peak concentration time (PCT; 24.3h) among markers. In comparison,
      fecal fiber-bound N ((15)NADF) had a considerably higher K1 (0.032/h) and lower
      TMRT (46.4 h) than (13)CADF. Total N (measured with (15)NDM) had a comparable K1
      (0.034/h) to that of (15)NADF but provided the highest fractional passage rates
      from the proximal colon-cecum (K2; 0.37/h) and lowest PCT (17.4 h) among markers.
      A literature review indicated unclear effects of grass silage maturity on K1 and
      unknown effects of N fertilization on K1. Our study indicated no effect of
      advancing maturity on fecal K1 and a trend for K1 to increase with the high level
      of N fertilization. Parameter K2 increased, whereas PCT and TMRT generally
      decreased with the high level of N fertilization. Omasal digesta sampling largely
      confirmed results based on fecal sampling. Results indicate that the use of
      delta(13)C and delta(15)N can describe fiber-specific passage kinetics of forage.

PMID- 24119807
TI  - Long-acting insulins alter milk composition and metabolism of lactating dairy
      cows.
AB  - This study investigated the effect of 2 different types of long-acting insulin on
      milk production, milk composition, and metabolism in lactating dairy cows.
      Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3
      treatments in a completely randomized design. Treatments consisted of control
      (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine
      (L). The H and L treatments were administered twice daily at 12-h intervals via
      subcutaneous injection for 10d. Cows were milked twice daily, and milk
      composition was determined every other day. Mammary biopsies were conducted on d
      11, and mammary proteins extracted from the biopsies were analyzed by Western
      blot for components of insulin and mammalian target of rapamycin signaling
      pathways. Treatment had no effect on dry matter intake or milk yield. Treatment
      with both forms of long-acting insulin increased milk protein content and tended
      to increase milk protein yield over the 10-d treatment period. Analysis of milk N
      fractions from samples collected on d 10 of treatment suggested that cows
      administered L tended to have higher yields of milk protein fractions than cows
      administered H. Milk fat content and yield tended to be increased for cows
      administered long-acting insulins. Lactose content and yields were decreased by
      treatment with long-acting insulins. Administration of long-acting insulins,
      particularly L, tended to shift milk fatty acid composition toward increased
      short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma
      concentrations of glucose and urea N were lower for cows administered long-acting
      insulins; interactions of treatment and sampling time were indicative of more
      pronounced effects of L than H on these metabolites. Concentrations of
      nonesterified fatty acids and insulin were increased in cows administered long
      acting insulins. Decreased concentrations of urea N in both plasma and milk
      suggested more efficient use of N in cows administered long-acting insulins.
      Western blot analysis of mammary tissue collected by biopsy indicated that the
      ratios of phosphorylated protein kinase b (Akt) to total Akt and phosphorylated
      ribosomal protein S6 (rpS6) to total rpS6 were not affected by long-acting
      insulins. Modestly elevating insulin activity in lactating dairy cows using long
      acting insulins altered milk composition and metabolism. Future research should
      explore mechanisms by which either insulin concentrations or insulin signaling
      pathways in the mammary gland can be altered to enhance milk fat and protein
      production.

PMID- 24119808
TI  - Dairy cows increase ingestive mastication and reduce ruminative chewing when
      grazing chicory and plantain.
AB  - Although the nutritive value of chicory (Cichorium intybus L.) and plantain
      (Plantago lanceolata L.) has been thoroughly studied, little is known about the
      grazing behavior of cattle feeding on chicory and plantain swards. The objective
      of the present study was to assess and describe the grazing behavior of dairy
      cows as affected by dietary proportions of chicory and plantain fed as
      monocultures for part of the day. Ninety Holstein-Friesian cows (489+/-42 kg of
      body weight; 4.1+/-0.3 body condition score, and 216+/-15 d in milk) were
      randomly assigned to 15 groups (6 cows per group) and grazed according to 7
      treatments: control (CTL, 3 groups), perennial ryegrass (Lolium perenne L.)
      dominant sward (24-h pasture strip); 3 chicory treatments comprising 20, 40, and
      60% of the diet, strip-grazing a monoculture of chicory to a fixed postgrazing
      residual before strip-grazing a perennial ryegrass dominant sward (2 groups of
      cows per treatment); and 3 plantain treatments comprising 20, 40, and 60% of the
      diet, strip-grazing a monoculture of plantain to a fixed postgrazing residual
      before strip-grazing a perennial ryegrass dominant sward (2 groups of cows per
      treatment). Four focal animals per group were equipped with 3-dimensional motion
      sensors, which provided the number of steps taken at each minute of the day.
      These cows were also fitted with automatic jaw-movement recorders that identified
      bites, mastication during ingestion, chewing during rumination, and determined
      grazing, rumination and idling times and bouts. Daily grazing time and bouts were
      not affected by treatments but rumination time differed and was reduced by up to
      90 min when cows were allocated to chicory and plantain as 60% of their diet.
      Ruminative chewing was reduced in cows grazing chicory and plantain by up to 20%
      in cows allocated to the 60% treatments. Compared with perennial ryegrass, as the
      dietary proportion of chicory and plantain increased, cows spent more time idling
      and less time ruminating, and increased ingestive mastications 5 and 3 times for
      chicory and plantain, respectively. Cows allocated to chicory and plantain
      reduced bite rate and bites per grazing step linearly, and increased the number
      of mastications per bite of pasture dry matter intake while grazing pasture after
      having grazed chicory and plantain. These results indicate that cows grazing
      chicory and plantain masticate more during ingestion and reduce rumination time
      and chewing. They also suggest that chicory presents greater constraints to
      ingestion than does plantain. Thus, although chicory has been considered to have
      a greater nutritive value than plantain, its overall feeding value may be no
      greater than that of plantain.

PMID- 24119809
TI  - Short communication: Goat colostrum quality: litter size and lactation number
      effects.
AB  - The quality of colostrum of Murciano-Granadina goats was studied to establish the
      transition period and the time when milk can be marketed. Forty-three dairy goats
      were used: 19 primiparous (15 single births; 4 multiple births) and 24
      multiparous (10 single births; 14 multiple births). Samples were collected every
      12h during the first week postpartum. Physicochemical parameters and somatic cell
      count were determined. Analysis of variance with repeated measures was used to
      study the effect of different factors: postpartum time, litter size, lactation
      number, their interactions, and production level on colostrum. Postpartum time
      had a significant effect on all parameters studied, which decreased along the
      first week of lactation, whereas lactose, pH, and conductivity increased. Based
      on these results, colostrum secretion takes place until 36 h postpartum (hpp). In
      relation to other factors of variation studied, the lactation number influenced
      most colostrum components, whereas the litter size only affected the pH value,
      protein and lactose content. The production level influenced only the protein and
      dry matter contents, with an inverse relationship. Milk produced during the
      period between 36 and 96 hpp is considered transition milk, which should not be
      commercialized. Milk collected after 4d postpartum (96 hpp) could be marketed,
      ensuring that its composition does not present a risk in the dairy industry.

PMID- 24119810
TI  - Mating programs including genomic relationships and dominance effects.
AB  - Computerized mating programs using genomic information are needed by breed
      associations, artificial-insemination organizations, and on-farm software
      providers, but such software is already challenged by the size of the
      relationship matrix. As of October 2012, over 230,000 Holsteins obtained genomic
      predictions in North America. Efficient methods of storing, computing, and
      transferring genomic relationships from a central database to customers via a web
      query were developed for approximately 165,000 genotyped cows and the subset of
      1,518 bulls whose semen was available for purchase at that time. This study,
      utilizing 3 breeds, investigated differences in sire selection, methods of
      assigning mates, the use of genomic or pedigree relationships, and the effect of
      including dominance effects in a mating program. For both Jerseys and Holsteins,
      selection and mating programs were tested using the top 50 marketed bulls for
      genomic and traditional lifetime net merit as well as 50 randomly selected bulls.
      The 500 youngest genotyped cows in the largest herd in each breed were assigned
      mates of the same breed with limits of 10 cows per bull and 1 bull per cow (only
      79 cows and 8 bulls for Brown Swiss). A dominance variance of 4.1 and 3.7% was
      estimated for Holsteins and Jerseys using 45,187 markers and management group
      deviation for milk yield. Sire selection was identified as the most important
      component of improving expected progeny value, followed by managing inbreeding
      and then inclusion of dominance. The respective percentage gains for milk yield
      in this study were 64, 27, and 9, for Holsteins and 73, 20, and 7 for Jerseys.
      The linear programming method of assigning a mate outperformed sequential
      selection by reducing genomic or pedigree inbreeding by 0.86 to 1.06 and 0.93 to
      1.41, respectively. Use of genomic over pedigree relationship information
      provided a larger decrease in expected progeny inbreeding and thus greater
      expected progeny value. Based on lifetime net merit, the economic value of using
      genomic relationships was >$3 million per year for Holsteins when applied to all
      genotyped females, assuming that each will provide 1 replacement. Previous mating
      programs required transferring only a pedigree file to customers, but better
      service is possible by incorporating genomic relationships, more precise mate
      allocation, and dominance effects. Economic benefits will continue to grow as
      more females are genotyped. 

PMID- 24119811
TI  - Purinergic signaling gene network expression in bovine polymorphonuclear
      neutrophils during the peripartal period.
AB  - An effective immune response relies on efficient activation of polymorphonuclear
      neutrophilic leukocytes (PMNL). The PMNL release cellular ATP in response to
      inflammatory mediators. Although extracellular ATP is rapidly degraded to
      adenosine, both compounds can readily bind to either the purinergic receptor P1
      (adenosine) or P2 (ATP). The P1 and P2 receptors are members of the G-protein
      coupled receptor family. The peripartal period is characterized by marked changes
      in metabolic and inflammatory status that are functionally related with immune
      responses in the cow. We evaluated the mRNA expression of genes associated with
      purinergic signaling in PMNL during the peripartal period. Seven multiparous
      Holstein cows were dried off at d -50 relative to expected parturition and fed a
      controlled-energy diet (net energy for lactation=1.24 Mcal/kg of dry matter) for
      ad libitum intake during the entire dry period. After calving, all cows were fed
      a common lactation diet (net energy for lactation=1.65 Mcal/kg of dry matter)
      until 30 d in milk. Blood PMNL collected at -10, 3, and 21 d in milk were used to
      study the expression of 22 genes associated with adhesion to endothelium,
      chemoattractant binding at the plasma membrane, and purinergic signaling. Other
      blood samples around calving were used to analyze concentrations of insulin,
      metabolites, and whole-blood phagocytosis. The expression of purinergic receptor
      P2Y, G-protein coupled, 2 (P2RY2) increased on d 3 and then decreased on d 21.
      This response suggested that ATP could play a role in the amplification of
      chemotactic signals. In contrast, the expression of genes encoding cell adhesion
      [selectin L (SELL) and selectin P ligand (SELPLG)], chemoattractant receptors
      [complement component 5a receptor 1 (C5AR1), IL-8 receptor alpha (CXCR1), IL-8
      receptor beta (CXCR2), and platelet-activating factor receptor (PTAFR)], and
      adenosine receptors [adenosine A1 receptor (ADORA1) and adenosine A3 receptor
      (ADORA3)] decreased between -10 and 3 d. The decrease coincided with a marked
      increase in blood nonesterified fatty acids and hydroxybutyrate concentrations,
      and a decrease in glucose and insulin concentrations. The increase in metabolites
      also was associated with greater expression of leukotriene B4 receptor (LTB4R) on
      d 3 and 21 compared with d -10, which is involved in inflammatory prostaglandin
      synthesis. Most chemoattractant receptors increased by 21 d, but cell adhesion
      genes and blood leukocyte phagocytosis was lower. The expression of adenosine A2a
      receptor (ADORA2A), which is associated with immunosuppression of PMNL and that
      of adenosine uptake channels [solute carrier family 29 (nucleoside transporters),
      member 1 (SLC29A1) and member 2 (SLC29A2)] and the nucleotidase adenosine
      deaminase (ADA) was greater at 3 and 21 d compared with -10d. The reduction in
      key immune responses, such as cell adhesion and chemotaxis, by bovine PMNL could
      partly be a function of changes in mRNA expression of genes associated with
      purinergic signaling.

PMID- 24119812
TI  - The effect of limited proteolysis by different proteases on the formation of whey
      protein fibrils.
AB  - Four proteases: trypsin, protease A, pepsin, and protease M were selected to
      modify whey protein concentrate (WPC) at a low degree of hydrolysis (0.1, 0.2,
      and 0.3%) before adjusting to pH 2.0 and heating at 90 degrees C to gain insight
      into the influence of proteolysis on fibril formation. The kinetics of fibril
      formation were performed on native and modified WPC using the fluorescent dye
      thioflavin T in conjunction with transmission electron microscopy and far-UV
      circular dichroism spectroscopy for the morphological and secondary structural
      analyses. The change in surface hydrophobicity and content of free sulfhydryl
      groups were also observed during the formation of fibrils for the native and
      modified WPC. The content of aggregation and thioflavin T kinetic data indicated
      that the ability of fibril formation was apparently different for WPC modified by
      the 4 proteases. Whey protein concentrate modified by trypsin aggregated more
      during heating and the fibril formation rate was faster than that of the native
      WPC. Whey protein concentrate modified by the other proteases showed slower
      aggregation with worse amyloid fibril morphology. Compared with the native WPC,
      the structure of WPC changed differently after being modified by proteases. The
      state of alpha-helix structure for modified WPC played the most important role in
      the formation of fibrils. Under the mild conditions used in this work, the alpha
      helix structure of WPC modified by trypsin caused little destruction and resulted
      in fibrils with good morphology; the content of alpha-helices for WPC modified by
      other proteases decreased to 36.19 to 50.94%; thus, fibril formation was
      inhibited. In addition, it was beneficial for the modified WPC to form fibrils
      such that the surface hydrophobicity increased and the content of free sulfhydryl
      groups slightly decreased during heating. 

PMID- 24119813
TI  - Increased papillae growth and enhanced short-chain fatty acid absorption in the
      rumen of goats are associated with transient increases in cyclin D1 expression
      after ruminal butyrate infusion.
AB  - We tested the hypothesis that the proliferative effects of intraruminal butyrate
      infusions on the ruminal epithelium are linked to upregulation in cyclin D1
      (CCND1), the cyclin-dependent kinase 4 (CDK4), and their possible association
      with enhanced absorption of short-chain fatty acids (SCFA). Goats (n=23) in 2
      experiments (Exp.) were fed 200 g/d concentrate and hay ad libitum. In Exp. 1,
      goats received an intraruminal infusion of sodium butyrate at 0.3 (group B, n=8)
      or 0 (group C, n=7) g/kg of body weight (BW) per day before morning feeding for
      28 d and were slaughtered 8 h after the butyrate infusion. In Exp. 2, goats (n=8)
      received butyrate infusion and feeding as in Exp. 1. On d 28, epithelial samples
      were biopsied from the antrium ruminis at 0, 3, and 7 h after the last butyrate
      infusion. In Exp. 1, the ruminal molar proportional concentration of butyrate
      increased in group B by about 110% after butyrate infusion and remained elevated
      for 1.5 h; thereafter, it gradually returned to the baseline (preinfusion) level.
      In group C, the molar proportional concentration of butyrate was unchanged over
      the time points. The length and width of papillae increased in B compared with C;
      this was associated with increased numbers of cells and cell layers in the
      epithelial strata and an increase in the surface area of 82%. The mRNA expression
      of CCND1 increased transiently at 3 h but returned to the preinfusion level at 7
      h following butyrate infusion in Exp. 2. However, it did not differ between B and
      C in Exp. 1, in which the ruminal epithelium was sampled at 8 h after butyrate
      infusion. The mRNA expression of the monocarboxylate transporter MCT4, but not
      MCT1, was stably upregulated in B compared with C. The estimated absorption rate
      of total SCFA (%/h) increased in B compared with C. We conclude that transient
      increases in cyclin D1 transcription contribute to butyrate-induced papillae
      growth and subsequently to the increased absorption of SCFA in the ruminal
      epithelium of goats.

PMID- 24119814
TI  - Effect of essential oils on ruminal fermentation and lactation performance of
      dairy cows.
AB  - Three experiments (Exp.) were conducted to study the effects of dietary addition
      of an essential oil product (EO) based on eugenol and cinnamaldehyde (0, control,
      or 525 mg/d of Xtract 6965; Pancosma SA, Geneva, Switzerland) on ruminal
      fermentation, total-tract digestibility, manure gas emissions, N losses, and
      dairy cow performance. In Exp. 1 and 3, the EO supplement was added to the
      vitamin-mineral premix. In Exp. 2, EO was top-dressed. Experiments 1 and 2 were
      crossover designs with 20 multiparous Holstein cows each (including 4 and 8
      ruminally cannulated cows, respectively) and consisted of two 28-d periods.
      Intake of dry matter did not differ between treatments. Most ruminal fermentation
      parameters were unaffected by EO. Concentrations of ammonia (Exp. 1), isobutyrate
      (Exp. 1 and 2), and isovalerate (Exp. 1) were increased by EO compared with the
      control. Apparent total-tract digestibility of nutrients was similar between
      treatments, except total-tract digestibility of neutral-detergent fiber, which
      was increased or tended to be increased by EO in Exp. 1 and 2. Manure emissions
      of ammonia and methane were unaffected by EO. Blood plasma and milk urea-N
      concentrations and urinary N losses were increased by EO compared with the
      control in Exp. 1, but not in Exp. 2. Average milk yield, 3.5% fat-corrected milk
      yield, and milk fat, protein, and lactose concentrations were unaffected by
      treatment. Urinary excretion of purine derivatives, a marker for microbial
      protein production in the rumen, was greater in cows receiving the EO diet in
      Exp. 1, but not in Exp. 2. In Exp. 3, 120 Holstein cows were grouped in pens of
      20 cows/pen in a 12-wk experiment to study production effects of EO. Dry matter
      intake, milk yield (a trend for a slight decrease with EO), milk components, milk
      urea N, and feed efficiency were similar between treatments. Results from these
      studies indicate that supplementing dairy cows with 525 mg/d of Xtract 6965 had
      moderate effects on ruminal fermentation, but consistently increased ruminal
      isobutyrate concentration and tended to increase total-tract digestibility of
      neutral-detergent fiber. Under the conditions of these experiments, Xtract 6965
      fed at 525 mg/d did not affect milk production or composition.

PMID- 24119815
TI  - Selection of tropical lactic acid bacteria for enhancing the quality of maize
      silage.
AB  - The objective of this study was to select lactic acid bacteria (LAB) strains
      isolated from silage and assess their effect on the quality of maize silage. The
      LAB strains were inoculated into aqueous extract obtained from maize to evaluate
      their production of metabolites and pH reduction. The ability to inhibit the
      pathogenic and silage-spoilage microorganisms' growth was evaluated. Nine LAB
      strains that showed the best results were assessed in polyvinyl chloride
      experimental silos. The inoculation of the LAB strains influenced the
      concentration of lactic and acetic acids and the diversity of Listeria. The
      inoculation of silages with Lactobacillus buchneri (UFLA SLM11 and UFLA SLM103
      strains) resulted in silages with greater LAB populations and improvements after
      aerobic exposure. The UFLA SLM11 and SLM103 strains identified as L. buchneri
      showed to be promising in the treatment of maize silage. 

PMID- 24119816
TI  - Copy number variation of PRAMEY across breeds and its association with male
      fertility in Holstein sires.
AB  - Multi-copy gene families are especially prevalent in the male-specific region
      (MSY) of the mammalian Y chromosome. Copy number variations (CNV) of these Y
      linked gene families have been shown to affect human and animal fertility. The
      PRAMEY (Preferentially expressed antigen in melanoma, Y-linked) gene family is a
      newly identified, bovid-specific Y-linked gene family, which codes for a
      cancer/testis antigen that is expressed predominantly in testis and various
      tumors. The PRAMEY gene family is believed to play an important role in
      spermatogenesis and male fertility in cattle. The objective of this study was to
      investigate the CNV of PRAMEY within and across breeds and to determine whether
      CNV was associated with reproductive traits in Holstein bulls. A quantitative
      real-time PCR method was applied to measure the copy number of PRAMEY among 460
      bulls using a Y-linked single copy gene, DDX3Y (DEAD box polypeptide 3, Y
      linked), as a reference. The median copy number of PRAMEY was 13, ranging from 2
      to 31. Significant variations in PRAMEY copy number were observed among 15 breeds
      investigated. Holstein bulls had the lowest median copy number (12), whereas
      Limousin bulls possessed the highest median copy number (26). Furthermore, bulls
      in the taurine lineage (13) had a significantly lower median copy number than
      those bulls in the indicine lineage (20). Association analysis revealed that
      PRAMEY copy number was correlated negatively with scrotal circumference (SC),
      relative scrotal circumference (RLSC), percentage of normal sperm (PNS), and
      nonreturn rate (NRR), but had no significant association with postthaw motility
      (PTM), incubated motility (IM), percentage of intact acrosome (PIA), sire
      conception rate (SCR), or relative breeding efficiency (RBE). The data from this
      study indicate that CNV of the PRAMEY gene family is associated with male
      reproductive traits and may serve as a valuable marker for sire fertility
      selection at an early age in cattle. 

PMID- 24119817
TI  - Peroxisome proliferator-activated receptor-gamma stimulates the synthesis of
      monounsaturated fatty acids in dairy goat mammary epithelial cells via the
      control of stearoyl-coenzyme A desaturase.
AB  - In rodents, peroxisome proliferator-activated receptor-gamma (PPARG) plays a
      crucial role in fatty acid (FA) metabolism through regulation of gene expression,
      including stearoyl-coenzyme A desaturase (SCD), which is the rate-limiting enzyme
      for the biosynthesis of monounsaturated FA. However, whether or how PPARG
      regulates the activity of mammary SCD in ruminants is unknown. This study
      explored the potential role of PPARG isoforms in regulating SCD mRNA expression
      in lactating goat mammary epithelial cells (GMEC). Using quantitative real-time
      PCR, we observed a positive correlation between PPARG and SCD expression in the
      goat mammary gland at peak lactation. Overexpression of both PPARG1 and PPARG2 in
      GMEC increased markedly the expression of SCD, the concentration of 16:1 and
      18:1, and the desaturation indices of 16:1 and 18:1. The PPARG ligand
      rosiglitazone further increased SCD expression and desaturation indices in GMEC,
      overexpressing PPARG1 and PPARG2. Incubation with rosiglitazone alone increased
      the expression of SCD, but did not alter the concentration of 16- to 18-carbon FA
      or their desaturation indices. The results provide evidence that PPARG regulates
      the expression and activity of SCD in GMEC. As such, PPARG may contribute to
      regulation of SCD and monounsaturated FA synthesis during lactation. 

PMID- 24119818
TI  - Effect of pH on technological parameters and physicochemical and texture
      characteristics of the pasta filata cheese Telita.
AB  - The objective of this study was to determine the effect of stretching pH on
      technological parameters and physicochemical and texture characteristics of the
      pasta filata cheese Telita. A no-brine cheese-making method was used to control
      both melting and stretching temperatures. Six vats of cheese, each with a
      different stretching pH (5.2, 5.3, 5.4, 5.5, 5.6, and 5.7), were made in 2h.
      Cheese-making was replicated using 2 different lots of milk. Differences in
      stretching pH significantly affected all variables evaluated; stretching
      temperature and pH were positively correlated. Technological parameters showed an
      inverse relationship between pH and acidity and a direct relationship between
      melting and stretching temperature. The yield was highest as the pH increased and
      ranged from 11.4 to 12.9 kg of cheese/100 kg of milk. Physicochemical
      characteristics showed the following: moisture 48.1 to 53.5% (soft and semi-hard
      cheese), fat 46.3 to 54.9% (dry basis, full-fat cheese), minerals 2.8 to 3.5%
      (dry basis), calcium content 0.5 to 1.0% (dry basis), sodium 0.38 to 0.78% (dry
      basis), and whiteness index 77.2 to 84.5. Texture parameters showed that as the
      stretching pH increased, hardness increased, adhesiveness decreased, cohesiveness
      decreased, springiness increased, and chewiness increased. Samples were grouped
      based on principal component analysis. Group 1 contained cheeses at pH 5.2 and
      5.3 and were better in terms of retention of components. Group 2 contained
      cheeses at pH 5.6 and 5.7. These cheeses attained the highest yields, were
      whitest, and presented the highest values for texture parameters except for
      adhesiveness and cohesiveness. The third group of cheeses at pH 5.4 and 5.5 were
      considered the best because they showed a good balance among all variables
      evaluated.

PMID- 24119819
TI  - Evaluation of internal reference genes for quantitative expression analysis by
      real-time reverse transcription-PCR in somatic cells from goat milk.
AB  - Reverse transcription (RT) quantitative real-time PCR (qPCR) is the most accurate
      and easy-to-perform technique to measure the expression level of a selected gene
      of interest by quantifying mRNA transcripts. The use of reference genes is
      commonly accepted as the most reliable approach to normalize RT-qPCR data and
      reduce possible errors generated in the quantification of gene expression. The
      optimal number and choice of reference genes are experimentally validated for
      specific tissues or cell types and experimental designs. To date, data on qPCR
      normalization in goats are scarce and the most suitable reference genes in this
      species have been identified for only a limited number of tissues. The aim of
      this study was to determine an optimal combination of stably expressed reference
      genes in caprine milk somatic cells (MSC) from healthy and infected mammary
      glands. For the purpose, we performed RT-qPCR for 10 commonly used reference
      genes from various functional classes and then determined their expression level
      in MSC from goats intramammary challenged with Staphylococcus aureus and in MSC
      from healthy controls, with a view to select genes whose stability would be
      unaffected under infection conditions. The geNorm and NormFinder algorithms were
      used for validating the reference genes. Furthermore, to demonstrate the
      importance of normalization of gene expression with appropriate reference genes,
      we tested the effect of using a combination of the least stable genes for
      expression analysis evaluation. On the basis of our evaluation, we recommend the
      use of a panel of reference genes that should include G6PD, YWHAZ, and ACTB for
      caprine MSC gene expression profiling. The expression of the 2 genes of interest,
      pentraxin-related protein (PTX3) and secreted phosphoprotein 1 (SPP1), was
      evaluated by RT-qPCR in all samples collected pre- and postinfection, and the
      recommended reference genes were used to normalize the data. Our study provides a
      validated panel of optimal reference genes for the identification of genes
      differentially expressed by qRT-PCR in caprine MSC. Moreover, we provided a set
      of intron-spanning primer sequences that could be suitable for gene expression
      experiments using SYBR Green chemistry on other caprine tissues and cells. 

PMID- 24119820
TI  - Endoscopically assisted laparoscopic local resection of gastric tumor.
AB  - BACKGROUND: Minimally invasive procedures have been applied in treatment of
      gastric submucosal tumors. Currently, combined laparoscopic - endoscopic
      rendezvous resection (CLERR) emerges as a new technique which further reduces
      operative invasiveness. CASE PRESENTATION: A-57-year-old female patient presented
      with epigastric pain. She was submitted to gastroscopy, which revealed a tumor
      located at the angle of His. Biopsy specimens demonstrated a leiomyoma. The
      patient underwent endoscopically assisted laparoscopic resection of the tumor.
      The operative time was 45 minutes. Diagnosis of leiomyoma was confirmed by the
      final histopathological examination. The patient had an uneventful postoperative
      recovery and was discharged on the 2nd postoperative day. CONCLUSION: Combined
      laparoscopic and endoscopic rendezvous resection appears as a promising
      alternative minimally invasive technique. It offers easy recognition of the
      tumor, regardless of location, safe dissection, and full thickness resection with
      adequate margins as well as less operative time.

PMID- 24119821
TI  - Food for thought: atrioventricular dissociation.

PMID- 24119822
TI  - 2-Stage free and pedicle jejunum for esophageal replacement after failed colon
      interposition for caustic injury in a 5 year-old child.

PMID- 24119823
TI  - Cognitive effects of methylphenidate and levodopa in healthy volunteers.
AB  - Our previous study showed enhanced declarative memory consolidation after acute
      methylphenidate (MPH) administration. The primary aim of the current study was to
      investigate the duration of this effect. Secondary, the dopaminergic contribution
      of MPH effects, the electrophysiological correlates of declarative memory, and
      the specificity of memory enhancing effects of MPH to declarative memory were
      assessed. Effects of 40 mg of MPH on memory performance were compared to 100mg of
      levodopa (LEV) in a placebo-controlled crossover study with 30 healthy
      volunteers. Memory performance testing included a word learning test, the
      Sternberg memory scanning task, a paired associates learning task, and a spatial
      working memory task. During the word learning test, event-related brain
      potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30
      min delay, but it improved 24 h delayed memory recall relative to PLA and LEV.
      Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and
      the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded
      response times on the Sternberg Memory Scanning task and improved performance on
      the Paired Associates Learning task, relative to LEV, but not PLA. Performance on
      the Spatial working memory task was not affected by the treatments. These
      findings suggest that MPH and LEV might have opposite effects on memory.

PMID- 24119824
TI  - Extended depth of focus with induced spherical aberration in light-adjustable
      intraocular lenses.
AB  - PURPOSE: To evaluate the quality of vision and depth of focus induced by
      controlled amounts of negative spherical aberration in patients implanted
      bilaterally with light-adjustable intraocular lenses. DESIGN: Prospective,
      nonrandomized clinical trial. METHODS: Seventeen patients were implanted and
      treated with appropriate spatial irradiance light profiles. One eye was set for
      emmetropia, and the fellow eye received an additional aspheric light treatment to
      induce controlled amounts of negative spherical aberration. We used a Hartmann
      Shack sensor to measure the eye's refraction and aberrations for a 4-mm pupil
      diameter. Decimal visual acuity (VA) was measured using a micro-display placed at
      10 m, 60 cm, 40 cm, and 30 cm. RESULTS: Eyes treated with aspheric profiles were
      divided into 2 groups depending on the final amount of induced negative spherical
      aberration: low [-0.05, -0.10 MUm] and high [-0.13, -0.23 MUm]. In both groups,
      the mean uncorrected decimal VA at 60 cm was over 0.90. In the first group,
      distance VA was 0.97 +/- 0.16, but in the second group it was lower (0.76 +/-
      0.16). As expected, the VA for nearer distances is higher in the eyes with a
      larger magnitude of spherical aberration (P value < .01): 0.94 +/- 0.10 and 0.73
      +/- 0.16 at 40 and 30 cm, respectively, in comparison with 0.71 +/- 0.15 and 0.50
      +/- 0.14. Binocular summation with the fellow eye, adjusted for emmetropia,
      produces an excellent binocular distance VA (>1.10) in both groups. CONCLUSIONS:
      Controlled amounts of negative spherical aberration and defocus can be induced in
      eyes implanted with adjustable intraocular lenses to enhance near vision.

PMID- 24119825
TI  - The enteroviruses: problems in need of treatments.
AB  - Specific antiviral therapy is currently not available for enterovirus (EV)
      infections. Poliomyelitis, EV 71 neurologic disease, and neonatal EV disease are
      three manifestations of EV infections that exemplify the importance of developing
      antivirals for EV infections. Despite tremendous strides in the effort to
      eradicate polio through vaccination, challenges remain, including the potential
      for transmission of neurovirulent vaccine-derived polioviruses which have
      genetically reverted from live-attenuated, oral poliovirus vaccine virus. EV 71
      emerged in the late 1990 s in eastern Asia as a neurovirulent virus that causes
      large outbreaks of hand-foot-mouth disease, herpangina, and fever, and, in some
      children, meningitis, acute flaccid paralysis, and brainstem encephalitis
      complicated by pulmonary edema and cardiopulmonary collapse. EV infections in
      neonates can cause severe disease characterized by meningoencephalitis,
      myocarditis, pneumonitis, and/or hepatitis and coagulopathy. Prototypic agents
      for specific therapy of EV infections that act upon numerous potential viral
      targets exist. Three candidate compounds are currently in development: pleconaril
      (active against many EVs), V-073 (anti-poliovirus), and BTA-798 (active against
      many rhinoviruses and EVs). The three conditions described illustrate why
      development of antiviral medications for EV infections is a medically important
      need.

PMID- 24119826
TI  - Nontuberculous mycobacterial infections in children with inborn errors of the
      immune system.
AB  - Severe mycobacterial disease is mostly confined to patients who are
      immunocompromized either by acquired or inherited causes. One such genetic
      disorder is Mendelian Susceptibility to Mycobacterial Disease (MSMD), a hot topic
      within the field of primary immunodeficiency. This single gene disorder is
      characterized by isolated infection with mycobacteria or Salmonella due to a
      defect in the type-1 cytokine response. In the last two decades, ten genes have
      been labeled as causing MSMD when they harbor germline mutations, namely IL12B,
      IL12RB1, IFNGR1, IFNGR2, STAT1, IKBKG, CYBB, TYK2, IRF8 and ISG15. The mutations
      lead to either insufficient production of IFN-gamma, or to an insufficient
      response to the cytokine. Current treatment options include recombinant IFN-gamma
      and hematologic stem cell transplantation (HSCT). In the future, gene therapy,
      antisense-mediated exon skipping and chemical intervention in glycosylation
      problems may become successful alternatives. Furthermore, it is likely that many
      new candidate genes and pathways crucial for mycobacterial immunity will be
      identified. 

PMID- 24119827
TI  - The challenge of enteric fever.
AB  - Enteric fever, a non-specific, systemic infection caused by S. Typhi or Paratyphi
      A, B or C, is common in resource-limited regions of the world, where poor
      sanitation infrastructure facilitates faeco-oral transmission. Prompt treatment
      with appropriate antibiotics minimises illness severity, but presentation to
      health care facilities is often delayed because of the non-specific nature of the
      symptoms and the lack of reliable diagnostic tests. Disease prevention requires
      significant investment in provision of clean water and sanitation in the long
      term; vaccination offers a more realistic strategy for medium term control.
      However, implementation of existing vaccines and development of more efficacious
      vaccines has been hindered by the lack of an established correlate of protection
      and under appreciation of the true disease burden. Human microbial infection
      studies could provide a vehicle for the rapid evaluation of novel vaccines and
      investigation of the immunobiology of enteric infection. 

PMID- 24119828
TI  - BK and JC virus: a review.
AB  - Polyomaviruses are ubiquitous, species-specific viruses belonging to the family
      Papovaviridae. The two most commonly known human polyomaviruses, BK virus and JC
      virus were first described in the 1970s. Newer human polyomaviruses, namely KI
      polyoma virus, WU polyoma virus and Merkel cell polyoma virus were identified in
      the last five years. Most humans encounter BK and JC virus during childhood,
      causing mild illness. However, when reactivated or acquired in the
      immunocompromised host, BK and JC virus have been implicated in a number of human
      clinical disease states. BK is most commonly associated with renal involvement,
      such as ureteral stenosis, hemorrhagic cystitis and nephropathy. Less commonly,
      it is associated with pneumonitis, retinitis, liver disease and
      meningoencephalitis. JC virus is most well known for its association with
      progressive multifocal leukoencephalopathy, and is possibly implicated in the
      development of various human neoplasms. The following chapter will outline the
      basic virology, epidemiology and clinical manifestations of BK and JC virus and
      discuss relevant diagnostic and treatment options. 

PMID- 24119829
TI  - Acute sinusitis in children: do antibiotics have any role?
AB  - Bacteria can be recovered from paranasal sinuses in the majority of patients
      given the diagnosis of acute bacterial sinusitis (ABS), and bacteriologic cure
      can be achieved with appropriate antibiotic treatment. The critical question is
      whether bacteriologic cure correlates with meaningful clinical endpoints such as
      clinical improvement, reduction in recurrent disease, or prevention of
      complications. Of the 4 pediatric placebo-controlled randomized clinical trials
      (PCRCTs), 2 suggest superiority of antibiotic treatment and 2 suggest lack of
      superiority. PCRCTs in adults are mixed as to clinical benefit. Pediatric and
      adult meta-analyses demonstrate modest benefit of antibiotic therapy and rates of
      spontaneous recovery without antibiotics of 60-65%. Although retrospective
      studies indicate that some patients who develop orbital or neurologic
      complications of sinusitis were pre-treated with antibiotic therapy, a low rate
      of complications precludes determination of whether antibiotic treatment prevents
      complications in some proportion of patients. Like the literature evidence,
      expert guideline recommendations are mixed. Although the evidence base is
      incomplete and conflicting, the limited data suggest that antibiotics probably do
      have a role in the treatment of pediatric ABS. The most compelling rationale is
      prevention of serious complications, but proof for this rationale is lacking. 

PMID- 24119830
TI  - Treatment of AVN using the induction chamber technique and a biological-based
      approach: indications and clinical results.
AB  - OBJECTIVE: To determine the efficacy of core decompression (CD) technique
      combined with recombinant morphogenetic proteins, autologous mesenchymal stem
      cells (MSCs) and xenograft bone substitute into the necrotic lesion of the
      femoral head on clinical symptoms and on the progression of osteonecrosis of the
      femoral head. PATIENTS AND METHODS: A total of 38 patients (40 hips) with early
      stage osteonecrosis of the femoral head were studied over a 4-year period.
      RESULTS: CD technique combined with recombinant morphogenetic proteins,
      autologous MSCs and xenograft bone substitute was associated with a significant
      reduction in both pain and joint symptoms and reduced the incidence of fractural
      stages. At 36 months, 33 patients achieved clinical and radiographic healing.
      CONCLUSION: This long-term follow-up study confirmed that CD technique combined
      with recombinant morphogenetic proteins, autologous MSCs and xenograft bone
      substitute may be an effective treatment for patients with early stage
      osteonecrosis of the femoral head.

PMID- 24119832
TI  - Stage presentation, care patterns, and treatment outcomes for squamous cell
      carcinoma of the penis.
AB  - PURPOSE: Penile squamous cell carcinoma (SCC) is a rare entity, with few
      published series on outcomes. We evaluated the stage distributions and outcomes
      for surgery and radiation therapy in a U.S. population database. METHODS AND
      MATERIALS: Subjects with SCC of the penis were identified using the National
      Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program
      database between 1988 and 2006. Descriptive statistics were performed, and cause
      specific survival (CSS) was estimated using Kaplan-Meier analysis. Comparisons of
      treatment modalities were analyzed using multivariate Cox regression. Subjects
      were staged using American Joint Committee on Cancer, sixth edition, criteria.
      RESULTS: There were 2458 subjects identified. The median age was 66.8 years
      (range, 17-102 years). Grade 2 disease was present in 94.5% of cases. T1, T2, T3,
      T4, and Tx disease was present in 64.8%, 17.1%, 9.5%, 2.1%, and 6.5% of cases,
      respectively. N0, N1, N2, N3, and Nx disease was noted in 61.6%, 6.9%, 4.0%,
      3.7%, and 23.8% of cases, respectively. M1 disease was noted in 2.5% of subjects.
      Individuals of white ethnicity accounted for 85.1% of cases. Lymphadenectomy was
      performed in 16.7% of cases. The CSS for all patients at 5 and 10 years was 80.8%
      and 78.6%. By multivariable analysis grades 2 and 3 disease, T3 stage, and
      positive lymph nodes were adverse prognostic factors for CSS. CONCLUSION: SCC of
      the penis often presents as early-stage T1, N0, M0, grade 1, or grade 2 disease.
      The majority of patients identified were treated with surgery, and only a small
      fraction of patients received radiation therapy alone or as adjuvant therapy.

PMID- 24119831
TI  - Particularities of hand and wrist complex injuries in polytrauma management.
AB  - Hand and wrist lesions are relatively common in polytraumatised patients. These
      subjects sustain a wide range of potential life-threatening conditions and hand
      and wrist injuries incurred are often not diagnosed or are insufficiently
      treated. Closed lesions are the most frequently missed diagnosis, but even severe
      open lesions may be incorrectly treated. Most of these hand and wrist injuries
      can have a strong negative impact on long-term quality of life, particularly when
      treatment of these injuries is poor or delayed. Orthopaedic and hand surgeons
      should be vigilant in their assessment and treatment of patients with multiple
      injuries and a global approach, based on the advanced trauma life support (ATLS)
      protocol, must be applied. The very common association of head, chest, abdomen,
      bone and soft-tissue lesions in the polytraumatised patient requires a
      multidisciplinary team approach from the beginning. The energy of trauma in these
      patients often causes complex injuries to the wrist and hand; these require
      correct treatment in terms of both timing and techniques. It is not possible to
      create a practical, useful guideline with a "one lesion-one solution" approach,
      because every case is different; therefore, this paper describes a spectrum of
      indications and techniques that may be useful in managing hand and wrist
      injuries, particularly in polytraumatised patients. 

PMID- 24119833
TI  - A randomized controlled trial of lorazepam to reduce liver motion in patients
      receiving upper abdominal radiation therapy.
AB  - PURPOSE: Reduction of respiratory motion is desirable to reduce the volume of
      normal tissues irradiated, to improve concordance of planned and delivered doses,
      and to improve image guided radiation therapy (IGRT). We hypothesized that
      pretreatment lorazepam would lead to a measurable reduction of liver motion.
      METHODS AND MATERIALS: Thirty-three patients receiving upper abdominal IGRT were
      recruited to a double-blinded randomized controlled crossover trial. Patients
      were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on
      day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1,
      followed by lorazepam 4 to 8 days later. After tablet ingestion and daily
      radiation therapy, amplitude of liver motion was measured on both study days. The
      primary outcomes were reduction in craniocaudal (CC) liver motion using 4
      dimensional kV cone beam computed tomography (CBCT) and the proportion of
      patients with liver motion <=5 mm. Secondary endpoints included motion measured
      with cine magnetic resonance imaging and kV fluoroscopy. RESULTS: Mean relative
      and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm
      respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with
      CBCT. Reduction in CC amplitude to <=5 mm residual liver motion was seen in 13%
      (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS);
      65% (95% CI 48%-81%) had reduction in residual CC liver motion to <=10 mm (vs 52%
      with placebo, P=NS). Patients with large respiratory movement and patients who
      took lorazepam >=60 minutes before imaging had greater reductions in liver CC
      motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and
      fluoroscopy were nonsignificant. CONCLUSIONS: Lorazepam reduces liver motion in
      the CC direction; however, average magnitude of reduction is small, and most
      patients have residual motion >5 mm.

PMID- 24119834
TI  - Intensity modulated proton beam radiation for brachytherapy in patients with
      cervical carcinoma.
AB  - PURPOSE: To evaluate intensity modulated proton therapy (IMPT) in patients with
      cervical cancer in terms of coverage, conformity, and dose-volume histogram (DVH)
      parameters correlated with recommendations from magnetic resonance imaging (MRI)
      guided brachytherapy. METHODS AND MATERIALS: Eleven patients with histologically
      proven cervical cancer underwent primary chemoradiation for the pelvic lymph
      nodes, the uterus, the cervix, and the parametric region, with a symmetric margin
      of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The
      prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a
      simultaneous boost. For several reasons, the patients were unable to undergo
      brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to
      the cervix, including the macroscopic tumor with an MRI-guided target definition,
      with an isotropic margin of 5 mm for planning target volume (PTV) definition.
      Groupe-Europeen de Curietherapie and European society for Radiotherapy and
      Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison
      plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the
      RapidArc (RA). RESULTS: The dose to the high-risk volume was calculated with
      alpha/beta = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean
      dose of 38.2 +/- 5.0 Gy (35.0 +/-1.8 Gy for RA). The D98% was 31.9 +/- 2.6 Gy
      (RA: 30.8 +/- 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose
      (EQD2) (alpha/beta = 3) to 2 cm(3) of the rectal wall, sigmoid wall, and bladder
      wall was 62.2 +/- 6.4 Gy, 57.8 +/- 6.1 Gy, and 80.6 +/- 8.7 Gy (for RA: 75.3 +/-
      6.1 Gy, 66.9 +/- 6.9 Gy, and 89.0 +/- 7.2 Gy, respectively). For the IMPT boost
      plans in combination with external beam radiation therapy, all DVH parameters
      correlated with <5% risk for grades 2 to 4 late gastrointestinal and
      genitourinary toxicity. CONCLUSION: In patients who are not eligible for
      brachytherapy, IMPT as a boost technique additionally to external beam radiation
      therapy provides good target coverage and conformity and superior DVH parameters,
      compared with recommendations to MRI-guided brachytherapy. For selected patients,
      IMPT might be a valid alternative to brachytherapy and also superior to reference
      VMAT plans.

PMID- 24119835
TI  - Implications of intercellular signaling for radiation therapy: a theoretical dose
      planning study.
AB  - PURPOSE: Recent in vitro results have shown significant contributions to cell
      killing from signaling effects at doses that are typically used in radiation
      therapy. This study investigates whether these in vitro observations can be
      reconciled with in vivo knowledge and how signaling may have an impact on future
      developments in radiation therapy. METHODS AND MATERIALS: Prostate cancer
      treatment plans were generated for a series of 10 patients using 3-dimensional
      conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric
      modulated arc therapy techniques. These plans were evaluated using mathematical
      models of survival following modulated radiation exposures that were developed
      from in vitro observations and incorporate the effects of intercellular
      signaling. The impact on dose-volume histograms and mean doses were evaluated by
      converting these survival levels into "signaling-adjusted doses" for comparison.
      RESULTS: Inclusion of intercellular communication leads to significant
      differences between the signalling-adjusted and physical doses across a large
      volume. Organs in low-dose regions near target volumes see the largest increases,
      with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT
      plans. By contrast, in high-dose regions, there is a small decrease in signaling
      adjusted dose due to reduced contributions from neighboring cells, with planning
      target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the
      dose distributions remain broadly similar, and comparisons between the treatment
      modalities are largely unchanged whether physical or signaling-adjusted dose is
      compared. CONCLUSIONS: Although incorporating cellular signaling significantly
      affects cell killing in low-dose regions and suggests a different interpretation
      for many phenomena, their effect in high-dose regions for typical planning
      techniques is comparatively small. This indicates that the significant signaling
      effects observed in vitro are not contradicted by comparison with clinical
      observations. Future investigations are needed to validate these effects in vivo
      and to quantify their ranges and potential impact on more advanced radiation
      therapy techniques.

PMID- 24119836
TI  - Health-related quality of life after stereotactic body radiation therapy for
      localized prostate cancer: results from a multi-institutional consortium of
      prospective trials.
AB  - PURPOSE: To evaluate the early and late health-related quality of life (QOL)
      outcomes among prostate cancer patients following stereotactic body radiation
      therapy (SBRT). METHODS AND MATERIALS: Patient self-reported QOL was
      prospectively measured among 864 patients from phase 2 clinical trials of SBRT
      for localized prostate cancer. Data from the Expanded Prostate Cancer Index
      Composite (EPIC) instrument were obtained at baseline and at regular intervals up
      to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short
      course of androgen deprivation therapy was given to 14% of patients. RESULTS:
      Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A
      transient decline in the urinary and bowel domains was observed within the first
      3 months after SBRT which returned to baseline status or better within 6 months
      and remained so beyond 5 years. The same pattern was observed among patients with
      good versus poor baseline function and was independent of the degree of early
      toxicities. Sexual QOL decline was predominantly observed within the first 9
      months, a pattern not altered by the use of androgen deprivation therapy or
      patient age. CONCLUSION: Long-term outcome demonstrates that prostate SBRT is
      well tolerated and has little lasting impact on health-related QOL. A transient
      and modest decline in urinary and bowel QOL during the first few months after
      SBRT quickly recovers to baseline levels. With a large number of patients
      evaluable up to 5 years following SBRT, it is unlikely that unexpected late
      adverse effects will manifest themselves.

PMID- 24119837
TI  - Challenges facing translational research organizations in China: a qualitative
      multiple case study.
AB  - BACKGROUND: Translational medicine is attracting much attention worldwide and
      many translational research organizations (TROs) have been established. In China,
      translational medicine has developed rapidly, but faces many challenges. This
      study was aimed at exploring these challenges faced by emerging TROs in China.
      METHOD: A qualitative, multiple case study approach was used to assess the
      challenges faced by TROs in China. Data were collected between May and August
      2012. RESULTS: Eight cases were identified. Overall, four themes that
      characterized TROs in China emerged from analyses: 1. objectives, organizer, and
      funding resources, 2. participating partners and research teams, 3. management,
      and 4. achievements. All TROs had objectives related to translating basic
      discovery to clinic treatment and cultivating translational researchers. In terms
      of organizer and funding resources, 7 out of 8 TROs were launched only by
      universities and/or hospitals, and funded mostly through research grants. As for
      participating partners and multidisciplinary research teams, all but one of the
      TROs only involved biomedical research institutions who were interested in
      translational research, and characterized as clinical research centers; 7 out of
      8 TROs involved only researchers from biomedicine and clinical disciplines and
      none involved disciplines related to education, ethnicity, and sociology, or
      engaged the community. Current management of the TROs were generally nested
      within the traditional research management paradigms, and failed to adapt to the
      tenets of translational research. Half of the TROs were at developmental stages
      defined as infrastructure construction and recruitment of translational
      researchers. CONCLUSIONS: TROs in China face the challenge of attracting
      sustainable funding sources, widening multidisciplinary cooperation, cultivating
      multi-disciplinary translational researchers and adapting current research
      management to translational research. Greater emphasis should be placed on
      increasing multidisciplinary cooperation, and innovating in education programs to
      cultivate of translational researchers. Efforts should be made to reform research
      management in TROs, and establish sustainable funding resources.

PMID- 24119838
TI  - Outbreak of Listeria monocytogenes in an urban poultry flock.
AB  - BACKGROUND: Listeria monocytogenes infection is most commonly recognized in
      ruminants, including cattle, sheep, and goats; but it is rarely diagnosed in
      poultry. This report describes an outbreak of L. monocytogenes in a backyard
      poultry flock. Also, it points out the importance of collaboration between
      veterinarians and public health departments and the possible implications of
      zoonotic diseases. CASE PRESENTATION: Depression, lack of appetite, labored
      breathing, and increased mortality were noted for 5 months in several affected
      birds within the flock. The pathologic changes in the internal organs of infected
      birds included severe myocarditis, pericarditis, pneumonia, hepatitis, and
      splenitis. No lesions were noted in the brain. Gram-positive organisms were seen
      in histologic sections of the heart and spleen. Listeria monocytogenes was
      detected by real time PCR from formalin fixed heart and spleen, and was isolated
      from fresh lung, spleen, and liver. This isolate was identified as L.
      monocytogenes serotype 4b by 16S rDNA sequencing and by PCR-based serotyping
      assay. CONCLUSIONS: This is the first report describing outbreak of L.
      monocytogenes in backyard poultry flock in Washington State and use of molecular
      methods to confirm L. monocytogenes infection from formalin fixed tissues.

PMID- 24119839
TI  - Medihoney: let nature do the work?

PMID- 24119840
TI  - Antibacterial honey for the prevention of peritoneal-dialysis-related infections
      (HONEYPOT): a randomised trial.
AB  - BACKGROUND: There is a paucity of evidence to guide the best strategy for
      prevention of peritoneal-dialysis-related infections. Antibacterial honey has
      shown promise as a novel, cheap, effective, topical prophylactic agent without
      inducing microbial resistance. We therefore assessed whether daily application of
      honey at the exit site would increase the time to peritoneal-dialysis-related
      infections compared with standard exit-site care plus intranasal mupirocin
      prophylaxis for nasal carriers of Staphylococcus aureus. METHODS: In this open
      label trial undertaken in 26 centres in Australia and New Zealand, participants
      undergoing peritoneal dialysis were randomly assigned in a 1:1 ratio with an
      adaptive allocation algorithm to daily topical exit-site application of
      antibacterial honey plus standard exit-site care or intranasal mupirocin
      prophylaxis (only in carriers of nasal S aureus) plus standard exit-site care
      (control group). The primary endpoint was time to first infection related to
      peritoneal dialysis (exit-site infection, tunnel infection, or peritonitis). The
      trial is registered with the Australian New Zealand Clinical Trials Registry,
      number 12607000537459. FINDINGS: Of 371 participants, 186 were assigned to the
      honey group and 185 to the control group. The median peritoneal-dialysis-related
      infection-free survival times were not significantly different in the honey (16.0
      months [IQR not estimable]) and control groups (17.7 months [not estimable];
      unadjusted hazard ratio 1.12, 95% CI 0.83-1.51; p=0.47). In the subgroup
      analyses, honey increased the risks of both the primary endpoint (1.85, 1.05
      3.24; p=0.03) and peritonitis (2.25, 1.16-4.36) in participants with diabetes.
      The incidences of serious adverse events (298 vs 327, respectively; p=0.1) and
      deaths (14 vs 18, respectively; p=0.9) were not significantly different in the
      honey and control groups. 11 (6%) participants in the honey group had local skin
      reactions. INTERPRETATION: The findings of this trial show that honey cannot be
      recommended routinely for the prevention of peritoneal-dialysis-related
      infections. FUNDING: Baxter Healthcare, Queensland Government, Comvita, and
      Gambro.

PMID- 24119841
TI  - Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent
      sustained innate immune signaling.
AB  - Activation of the stimulator of interferon genes (STING) pathway by microbial or
      self-DNA, as well as cyclic dinucleotides (CDNs), results in the induction of
      numerous genes that suppress pathogen replication and facilitate adaptive
      immunity. However, sustained gene transcription is rigidly prevented to avoid
      lethal STING-dependent proinflammatory disease by mechanisms that remain unknown.
      We demonstrate here that, after autophagy-dependent STING delivery of TANK
      binding kinase 1 (TBK1) to endosomal/lysosomal compartments and activation of
      transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB, STING
      is subsequently phosphorylated by serine/threonine UNC-51-like kinase
      (ULK1/ATG1), and IRF3 function is suppressed. ULK1 activation occurred following
      disassociation from its repressor AMP activated protein kinase (AMPK) and was
      elicited by CDNs generated by the cGAMP synthase, cGAS. Thus, although CDNs may
      initially facilitate STING function, they subsequently trigger negative-feedback
      control of STING activity, thus preventing the persistent transcription of innate
      immune genes. 

PMID- 24119842
TI  - Generation and dynamics of an endogenous, self-generated signaling gradient
      across a migrating tissue.
AB  - In animals, many cells reach their destinations by migrating toward higher
      concentrations of an attractant. However, the nature, generation, and
      interpretation of attractant gradients are poorly understood. Using a GFP fusion
      and a signaling sensor, we analyzed the distribution of the attractant chemokine
      Sdf1 during migration of the zebrafish posterior lateral line primordium, a
      cohort of about 200 cells that migrates over a stripe of cells uniformly
      expressing sdf1. We find that a small fraction of the total Sdf1 pool is
      available to signal and induces a linear Sdf1-signaling gradient across the
      primordium. This signaling gradient is initiated at the rear of the primordium,
      equilibrates across the primordium within 200 min, and operates near steady
      state. The rear of the primordium generates this gradient through continuous
      sequestration of Sdf1 protein by the alternate Sdf1-receptor Cxcr7. Modeling
      shows that this is a physically plausible scenario.

PMID- 24119844
TI  - [Impact of a small-group educational intervention for 4- to 12-year-old asthmatic
      children and their parents on the number of healthcare visits and quality of
      life].
AB  - INTRODUCTION: Asthma is the most frequent chronic disease in children. Many
      educational approaches to asthma exist, but there is no evidence of their
      effectiveness because of the heterogeneity of practices. Several studies show
      that good knowledge of the disease associated with personal skills and optimal
      medication improve treatment compliance and decrease school absenteism and asthma
      exacerbations. The "Asthma School" conducted in the Children's Hospital of
      Lausanne, Switzerland is in keeping with these recommendations. The aim of the
      study was to evaluate the impact of Asthma School (therapeutic education) on the
      number of medical visits in asthmatic children. We also assessed the quality of
      life of children and their caregivers. METHODS: We included in a prospective
      longitudinal study every child aged 4 to 12 years and their parents attending
      Asthma School over 1 year and followed them at 6 months. The number of emergency
      visits, medical appointments, and hospitalizations during the year before and
      after Asthma School was assessed with a questionnaire administered to the family
      physicians (GPs, pediatricians). Quality of life was evaluated with the
      Paediatric Asthma Quality of Life Questionnaire (PAQLQ) at inclusion and 6 months
      after. RESULTS: Twenty-seven children and their parents were included. The mean
      age was 7.02 years. Pediatric visits, emergency visits, and hospitalizations
      decreased significantly between the year before and the year after Asthma School.
      Emergency visits were 41, 1 year before Asthma School and 21, 1 year after it,
      medical appointments were 62 vs 30, and hospitalizations were 17 vs 2,
      respectively. The Wilcoxon sign-rank test demonstrates a significant difference
      with P=0.010 for medical appointments, P=0.021 for emergency visits, and P=0.002
      for hospitalizations. Quality of life in children improved in all domains but one
      evaluated by the PAQLQ(S) (score of 5.90 vs 6.52). Parental quality of life
      (PACQLQ) improved in all domains (overall score of 5.21 vs 6.15). CONCLUSION:
      Interactive education on asthma improves clinically important outcomes and
      quality of life in children and their families. The skills acquired allow them to
      manage daily life.

PMID- 24119845
TI  - Chronic kidney disease in African Americans: past, present, and future:
      introduction.

PMID- 24119843
TI  - Super-enhancers in the control of cell identity and disease.
AB  - Super-enhancers are large clusters of transcriptional enhancers that drive
      expression of genes that define cell identity. Improved understanding of the
      roles that super-enhancers play in biology would be afforded by knowing the
      constellation of factors that constitute these domains and by identifying super
      enhancers across the spectrum of human cell types. We describe here the
      population of transcription factors, cofactors, chromatin regulators, and
      transcription apparatus occupying super-enhancers in embryonic stem cells and
      evidence that super-enhancers are highly transcribed. We produce a catalog of
      super-enhancers in a broad range of human cell types and find that super
      enhancers associate with genes that control and define the biology of these
      cells. Interestingly, disease-associated variation is especially enriched in the
      super-enhancers of disease-relevant cell types. Furthermore, we find that cancer
      cells generate super-enhancers at oncogenes and other genes important in tumor
      pathogenesis. Thus, super-enhancers play key roles in human cell identity in
      health and in disease. 

PMID- 24119846
TI  - Racial disparities in kidney disease outcomes.
AB  - Chronic kidney disease (CKD) is a national public health problem. Although the
      prevalence of early stages of CKD is similar across different racial/ethnic and
      socioeconomic groups, the prevalence of end-stage renal disease is greater for
      minorities than their non-Hispanic white peers. Paradoxically, once on dialysis,
      minorities experience survival rates that exceed their non-Hispanic white peers.
      Advancing our understanding of the unique interplay of biological, genetic,
      environmental, sociocultural, and health care system level factors may prompt
      reorientation of our approach to health promotion and disease prevention. The
      potential of this new approach is to create previously unimagined gains to
      improve patient outcomes and reduce health inequities for patients with CKD. 

PMID- 24119847
TI  - Role of vitamin D receptor activation in racial disparities in kidney disease
      outcomes.
AB  - African Americans have lower 25-hydroxyvitamin D (25(OH)D) levels compared with
      whites. African Americans also have a higher risk of developing albuminuria and
      end-stage renal disease but a lower risk of death once they commence hemodialysis
      compared with whites. Vitamin D levels have been associated with multiple
      outcomes including albuminuria, progression to end-stage renal disease, and all
      cause and cardiovascular mortality. In this review, we examine the evidence
      linking 25(OH)D to outcomes and the possibility that differential 25(OH)D may
      explain certain racial differences in outcomes. 

PMID- 24119848
TI  - APOL1 and nephropathy progression in populations of African ancestry.
AB  - Marked familial aggregation of chronic kidney disease suggests that inherited
      factors play a major role in nephropathy susceptibility. Molecular genetics
      analyses have identified a number of genes reproducibly associated with a broad
      range of renal phenotypes. Most associations show polygenic inheritance patterns
      with limited effect size. In contrast, genetic association between the
      apolipoprotein L1 (APOL1) gene and several severe nondiabetic forms of kidney
      disease in African Americans approach Mendelian inheritance patterns and account
      for a large proportion of glomerulosclerosis in populations of African ancestry.
      Emerging data support an important role for APOL1 in the progression of diverse
      etiologies of kidney disease, in concert with requisite environmental
      (gene*environment) and inherited (gene*gene) interactions. This article reviews
      the current status of APOL1-associated nephropathy and discusses research
      questions under active investigation in the search for a cure for these severe
      and often progressive kidney diseases. 

PMID- 24119849
TI  - Vitamin D receptor signaling in renal and cardiovascular protection.
AB  - The high prevalence of vitamin D deficiency in patients with chronic kidney
      disease is believed to be an important risk factor for the cardiorenal syndrome
      commonly seen in this patient population. African Americans suffer a
      disproportionally high incidence of renal and cardiovascular disease with poor
      disease outcome, which may be partly attributed to their low vitamin D status in
      part owing to low subcutaneous photoproduction of vitamin D. Mounting evidence
      from animal and clinical studies has shown beneficial effects of vitamin D
      therapy on the renal and cardiovascular systems, and the underlying
      renoprotective and cardioprotective mechanisms of vitamin D receptor (VDR)
      mediated signaling are under intense investigation. In this article, our most
      recent understanding of the renal protective mechanism of the podocyte VDR
      signaling against diabetic nephropathy and the anti-atherosclerotic role of
      macrophage VDR signaling in the regulation of atherosclerosis is reviewed. 

PMID- 24119851
TI  - Race and the insulin resistance syndrome.
AB  - Type 2 diabetes remains an important cause of morbidity and mortality. The
      metabolic syndrome affects 25% of the adult US population based on the Third
      Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood
      Cholesterol in Adults from the National Cholesterol Education Program. Knowledge
      on the impact of obesity on metabolic health parameters has increased greatly
      over the past decade. This review discusses the limitations of the National
      Cholesterol Education Program metabolic syndrome definition and the racial
      disparities in the clinical presentation of the insulin resistance syndrome. We
      also examine the current literature with particular emphasis on albuminuria,
      nonalcoholic fatty liver disease, and intramyocellular lipid content. This review
      explores potential environmental and genetic reasons for differences in the
      manifestation of insulin resistance across racial/ethnic groups and highlights
      several promising areas for further study. 

PMID- 24119850
TI  - Fibroblast growth factor 23, vitamin D, and health disparities among African
      Americans with chronic kidney disease.
AB  - Compared with Caucasians, African Americans have lower circulating concentrations
      of 25-hydroxyvitamin D (25(OH)D), the major storage form of vitamin D, leading to
      the widespread assumption that African Americans are at higher risk of vitamin D
      deficiency. However, the finding that African Americans maintain better indices
      of musculoskeletal health than Caucasians throughout their lifespan despite
      having lower circulating 25(OH)D concentrations suggests that the relationship
      between vitamin D deficiency and racial health disparities may not be so
      straightforward. The fairly recent emergence of fibroblast growth factor 23
      (FGF23) may help resolve some of this uncertainty. FGF23 strongly modulates both
      systemic and local activation of 25(OH)D, playing a potentially important role in
      the degree to which lower 25(OH)D concentrations impact health outcomes,
      including differences in the incidence and rate of progression of chronic kidney
      disease by race. This review critically assesses ongoing controversies
      surrounding the relationship between vitamin D and racial disparities in chronic
      kidney disease outcomes, and how FGF23 may help to clarify the picture. 

PMID- 24119852
TI  - Socioeconomic factors and racial disparities in kidney disease outcomes.
AB  - African Americans suffer disproportionately from advanced and progressive chronic
      kidney disease (CKD). Socioeconomic factors are believed to play an important
      role in this disparity, and likely influence African Americans' increased risk of
      CKD through multiple pathways. Low socioeconomic status (SES) may contribute to
      racial disparities in CKD because of the greater prevalence of poverty, for
      example, among African Americans as compared with whites. However, low SES has a
      stronger relation with CKD among African Americans than among whites,
      underscoring that the context and magnitude of socioeconomic influences on CKD
      outcomes varies between these populations. These socioeconomic influences may
      produce new or potentiate existing racial differences in biology. This review
      discusses what is known about the role of SES in explaining racial disparities in
      CKD, highlights several knowledge gaps in this area, and suggests future
      directions toward the elimination of disparities in CKD. 

PMID- 24119853
TI  - Wilson's disease, 100 years later....
AB  - Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous
      disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of
      his descriptions in the light of the current knowledge. Wilson's invocation of an
      "unknown toxin" appears today as a prophetic intuition as the presence of excess
      copper in the liver was mentioned for the first time a year later whereas the
      role of copper in this disease was not described until 1929. Progress has been
      made to better understand the physiology of Wilson's disease (WD). The ATP7B gene
      implicated in WD is located on chromosome 13 and more than 500 mutations and 100
      polymorphisms have been to date identified. The phenotypic expression is highly
      variable, even within a family. This can partly be explained by environmental
      factors as nutrition. Modulator genes are also involved in the phenotypic
      expression of the disease. Most of symptoms observed in WD have already been
      described in detail by Wilson in 1912, but subsequent progress was made over the
      following 100 years, helping the physician diagnose WD. Hepatic and neurological
      symptoms are the most frequent expressions of the disease. Other extrahepatic
      features include renal manifestations, osteoarticular disorders, myocardial
      abnormalities, endocrine disturbances, realizing a multisystemic disease. The
      diagnosis of the disease is based on a combination of clinical symptoms,
      biological, radiological and genetic data and new tools (Brain MRI, relative
      exchangeable copper...) allow reducing delay to diagnosis. Therapeutic findings
      have also changed the disease prognosis. Treatment is based on the use of copper
      chelators to promote copper excretion from the body (D-penicillamine and
      Triethylenetetramine) and zinc salts to reduce copper absorption.
      Tetratiomolybdate appears to be a promising treatment. While significant progress
      has been made during this century, many physiological aspects of this disease
      remain unknown and require further research to find answers in the next 100
      years. 

PMID- 24119854
TI  - Mitochondrial dysfunctions in Parkinson's disease.
AB  - Neurodegenerative disorders (ND) include a wide spectrum of diseases
      characterized by progressive neuronal dysfunctions or degeneration. With an
      estimated cost of 135 billion ? in 2010 in the European Union (Olesen et al.,
      2012), they put an enormous economic as well as social burden on modern
      societies. Hence, they have been the subject of a huge amount of research for the
      last fifty years. For many of these diseases, our understanding of their profound
      causes is incomplete and this hinders the discovery of efficient therapies. ND
      form a highly heterogeneous group of diseases affecting various neuronal
      subpopulations reflecting different origins and different pathological
      mechanisms. However, some common themes in the physiopathology of these disorders
      are emerging. There is growing evidence that mitochondrial dysfunctions play a
      pivotal role at some point in the course of neurodegeneration. In some cases
      (e.g. Alzheimer's disease, amyotrophic lateral sclerosis), impairment of
      mitochondrial functions probably occurs late in the course of the disease. In a
      subset of ND, current evidence suggests that mitochondrial dysfunctions play a
      more seminal role in neuronal demise. Parkinson's disease (PD) presents one of
      the strongest cases based in part on post-mortem studies that have shown
      mitochondrial impairment (e.g. reduced complex I activity) and oxidative damage
      in idiopathic PD brains. The occurrence of PD is largely sporadic, but clinical
      syndromes resembling sporadic PD have been linked to specific environmental
      insults or to mutations in at least 5 distinct genes (alpha-synuclein, parkin, DJ
      1, PINK1 and LRRK2). It is postulated that the elucidation of the pathogenic
      mechanisms underlying the selective dopaminergic degeneration in familial and
      environmental Parkinsonism should provide important clues to the pathogenic
      mechanisms responsible for idiopathic PD. Hence, numerous cellular and animal
      models of the disease have been generated that mimic these environmental or
      genetic insults. The study of these models has yielded valuable information
      regarding the pathogenic mechanisms underlying dopaminergic degeneration in PD,
      many of which point towards an involvement of mitochondrial dysfunction. In this
      short review we will analyze critically the experimental evidence for the
      mitochondrial origin of PD and evaluate its relevance for our general
      understanding of the disease.

PMID- 24119855
TI  - [Symptomatic giant Virchow-Robin spaces].
AB  - INTRODUCTION: Perivascular spaces, known as Virchow-Robin spaces (VRS), may
      become massively enlarged but are usually an incidental finding. However, a few
      reports on patients with unusually large VRS have mentioned association with
      neurological symptoms. We report a series of three symptomatic patients with
      extremely wide Virchow-Robin spaces documented on brain magnetic resonance
      imaging (MRI). METHODS: We retrospectively analyzed the medical records and brain
      MRI of three symptomatic patients, who had been diagnosed with VRS widening. CASE
      REPORTS: In all three patients, the unusual widening of the VRS was located
      within the subcortical white matter with asymmetric distribution. Their
      neurological symptoms were epilepsy and neurological deficits which correlated
      well with the lesions seen on the MRI. Two patients had associated white matter
      hyperintensities: in the first case associated gliosis and in the second case,
      with vascular leukoencephalopathy. CONCLUSIONS: Enlarged symptomatic VRS are
      rare. The underlying pathophysiological mechanisms remain uncertain. We report
      three cases with symptomatic giant dilatation of the Virchow-Robin spaces.

PMID- 24119856
TI  - Effects of problem solving therapy on mental health outcomes in family caregivers
      of persons with a new diagnosis of mild cognitive impairment or early dementia: a
      randomized controlled trial.
AB  - OBJECTIVE: Interventions directed at the mental health of family dementia
      caregivers may have limited impact when focused on caregivers who have provided
      care for years and report high burden levels. We sought to evaluate the mental
      health effects of problem-solving therapy (PST), designed for caregivers of
      individuals with a recent diagnosis of Mild Cognitive Impairment (MCI) or early
      dementia. METHOD: Seventy-three (43 MCI and 30 early dementia) family caregivers
      were randomly assigned to receive PST or a comparison condition (nutritional
      education). Depression, anxiety, and problem-solving orientation were assessed at
      baseline and at 1, 3, 6, and 12 months post intervention. RESULTS: In general,
      the PST caregiver intervention was feasible and acceptable to family caregivers
      of older adults with a new cognitive diagnosis. Relative to nutritional
      education, PST led to significantly reduced depression symptoms, particularly
      among early dementia caregivers. PST also lowered caregivers' anxiety levels, and
      led to lessening of negative problem orientation. DISCUSSION: Enhanced problem
      solving skills, learned early after a loved one's cognitive diagnosis (especially
      dementia), results in positive mental health outcomes among new family
      caregivers.

PMID- 24119858
TI  - Antidepressant treatment of melancholia in older adults.
AB  - OBJECTIVE: This is the first prospective trial in an outpatient sample comparing
      the effect of nortriptyline with sertraline in the treatment of depression with
      and without melancholia. We hypothesized that patients with melancholia would
      respond better to nortriptyline than sertraline, whereas among patients without
      melancholia, nortriptyline and sertraline would have equal efficacy. METHODS: We
      conducted a randomized 12-week trial comparing sertraline with nortriptyline in
      the treatment of patients with nonpsychotic, unipolar major depression stratified
      by the presence of melancholia. One hundred ten unipolar depressed patients with
      and without melancholia comprised our intent-to-treat sample. Seventy-two were
      nonmelancholic depressed and randomly assigned to treatment with sertraline (N =
      40) or nortriptyline (N = 32). Thirty-eight were melancholic depressed and
      randomly assigned to treatment with sertraline (N = 18) or nortriptyline (N =
      20). RESULTS: The test of the interaction of medication group and melancholia
      status on response was not statistically significant. Among patients with
      melancholia, response rates were 47% to sertraline and 75% to nortriptyline,
      whereas among patients without melancholia, response rates were 51% to sertraline
      and 42% to nortriptyline. The odds of response for patients with melancholia
      treated with nortriptyline compared with sertraline was 3.46. The odds of
      response for patients without melancholia treated with sertraline compared with
      nortriptyline was 0.69. Similar findings were obtained in the remission and
      continuous outcome analyses. CONCLUSION: This study did not find a significant
      difference between sertraline and nortriptyline in the treatment of depressed
      older adults with melancholia.

PMID- 24119859
TI  - Successful ingredients in the SMILE study: resident, staff, and management
      factors influence the effects of humor therapy in residential aged care.
AB  - OBJECTIVE: To test the hypothesis that individual and institutional-level factors
      influence the effects of a humor therapy intervention on aged care residents.
      METHODS: Data were from the humor therapy group of the Sydney Multisite
      Intervention of LaughterBosses and ElderClowns, or SMILE, study, a single-blind
      cluster randomized controlled trial of humor therapy conducted over 12 weeks;
      assessments were performed at baseline, week 13, and week 26. One hundred eighty
      nine individuals from 17 Sydney residential aged care facilities were randomly
      allocated to the humor therapy intervention. Professional performers called
      "ElderClowns" provided 9-12 weekly humor therapy 2-hour sessions, augmented by
      trained staff, called "LaughterBosses." Outcome measures were as follows: Cornell
      Scale for Depression in Dementia, Cohen-Mansfield Agitation Inventory,
      Neuropsychiatric Inventory, the withdrawal subscale of Multidimensional
      Observation Scale for Elderly Subjects, and proxy-rated quality of life in
      dementia population scale. Facility-level measures were as follows: support of
      the management for the intervention, commitment levels of LaughterBosses,
      Environmental Audit Tool scores, and facility level of care provided (high/low).
      Resident-level measures were engagement, functional ability, disease severity,
      and time-in-care. Multilevel path analyses simultaneously modeled resident
      engagement at the individual level (repeated measures) and the effects of
      management support and staff commitment to humor therapy at the cluster level.
      RESULTS: Models indicated flow-on effects, whereby management support had
      positive effects on LaughterBoss commitment, and LaughterBoss commitment
      increased resident engagement. Higher resident engagement was associated with
      reduced depression, agitation, and neuropsychiatric scores. CONCLUSION:
      Effectiveness of psychosocial programs in residential aged care can be enhanced
      by management support, staff commitment, and active resident engagement.

PMID- 24119857
TI  - Unmet need for mental health care among veterans receiving palliative care:
      assessment is not enough.
AB  - OBJECTIVE: To determine whether inpatient palliative care teams' assessments of
      psychological distress affect receipt of in-hospital mental health care
      (psychotherapy, psychological support, and health and behavior interventions) for
      seriously ill veterans. METHODS: Retrospective review of medical records from 287
      seriously ill veterans who received inpatient palliative care consults between
      2008 and 2010 in the NY/NJ Veterans Healthcare Network. RESULTS: Of the veterans
      who were cognitively or physically able to answer questions on the Condensed
      Memorial Symptom Assessment Scale, 44% reported psychological distress. Of those
      with distress, 38% accessed mental health care. In logistic regression models
      adjusted for sociodemographic and health characteristics, there was no evidence
      that psychological distress reported during the palliative care consult was
      associated with subsequent mental health care receipt from any type of provider.
      CONCLUSIONS: Efforts to increase mental health care to psychologically distressed
      palliative care patients need to convert assessments into receipt of needed care.

PMID- 24119860
TI  - Reliability and validity of the Executive Interview (EXIT) and Quick EXIT among
      community dwelling older adults.
AB  - OBJECTIVES: To investigate the psychometric properties of the Executive Interview
      (EXIT) and Quick EXIT in community dwelling older adults. DESIGN: Secondary
      analysis of data obtained as part of a longitudinal study of cognitive function
      in late-life depression. SETTING: A university hospital. PARTICIPANTS: Community
      dwelling adults (N = 422), aged 59 years and older, with current or recent
      history of non-psychotic unipolar major depression, and never-depressed
      comparison subjects. MEASUREMENTS: The EXIT and other measures of executive
      control functions (ECF), non-executive cognitive domains, and global cognitive
      function. We calculated Quick EXIT scores from the EXIT. RESULTS: The EXIT
      demonstrated high inter-rater reliability (Intraclass correlation coefficient =
      0.978, F(7, 21) = 174.85, p <0.001), and both the EXIT and Quick EXIT
      demonstrated moderate internal consistency (alpha = 0.66 and alpha = 0.68,
      respectively). Both tests also demonstrated acceptable convergent validity
      against several standard tests of ECF (rs -0.399 to 0.322, except for the Trail
      Making Test B, where rs was 0.057 to 0.063) as well as against measures of
      multifactorial cognitive function (rs -0.432 to 0.491). Both tests, however,
      demonstrated inconsistent discriminant validity against a variety of standard non
      ECF tests (rs -0.013 to 0.376). CONCLUSIONS: Both the EXIT and the Quick EXIT
      have adequate reliability and appear to require ECF in this population. However,
      both the EXIT and the Quick EXIT also reflect non-ECF domains. The EXIT and Quick
      EXIT should be considered to be measures of global cognitive function rather than
      pure ECF measures. Given similar reliability and validity, the Quick EXIT is
      recommended clinically as it is briefer and less burdensome than the full EXIT.

PMID- 24119861
TI  - Connectivity underlying emotion conflict regulation in older adults with 5-HTTLPR
      short allele: a preliminary investigation.
AB  - OBJECTIVE: The serotonin transporter polymorphism short (s) allele is associated
      with heightened emotional reactivity and reduced emotion regulation, which
      increases vulnerability to depression and anxiety disorders. We investigated
      behavioral and neural markers of emotion regulation in community-dwelling older
      adults, contrasting s allele carriers and long allele homozygotes. METHODS:
      Participants (N = 26) completed a face-word emotion conflict task during
      functional magnetic resonance imaging, in which facilitated regulation of emotion
      conflict was observed on face-word incongruent trials following another
      incongruent trial (i.e., emotional conflict adaptation). RESULTS: There were no
      differences between genetic groups in behavioral task performance or neural
      activation in postincongruent versus postcongruent trials. By contrast,
      connectivity between dorsal anterior cingulate cortex (ACC) and pregenual ACC,
      regions previously implicated in emotion conflict regulation, was impaired in s
      carriers for emotional conflict adaptation. CONCLUSION: This is the first
      demonstration of an association between serotonin transporter polymorphism and
      functional connectivity in older adults. Poor dorsal ACC-pregenual ACC
      connectivity in s carriers may be one route by which these individuals experience
      greater difficulty in implementing effective emotional regulation, which may
      contribute to their vulnerability for affective disorders.

PMID- 24119862
TI  - Reliability and validity of a self-rated analogue scale for global measure of
      successful aging.
AB  - OBJECTIVE: Dimension-specific objective measures are criticized for their limited
      perspective and failure to endorse subjective perceptions by respondents, but the
      validity and correlates of a subjective global measure of successful aging (SA)
      are still not well established. We evaluated the reliability and validity of a
      self-rated analogue scale of global SA in an elderly Singaporean population.
      DESIGN: Cross-sectional data analysis using a comprehensive questionnaire survey.
      PARTICIPANTS AND SETTING: 489 community-dwelling Singaporeans aged 65 years and
      over. MEASUREMENTS: Self-rated SA on an analogue scale from 1 (least successful)
      to 10 (most successful) was analyzed for its relationship to criterion-based
      measures of five specific dimensions (physical health and function, mental well
      being, social engagement, psychological well-being, and
      spirituality/religiosity), as well as outcome measures (life satisfaction and
      quality of life). RESULTS: Self-rated SA was significantly correlated to measures
      of specific dimensions (standardized beta from 0.11 to 0.39), most strongly with
      psychological functioning (beta = 0.391). The five dimension-specific measures
      together accounted for 16.7% of the variance in self-rated SA. Self-rated SA best
      predicted life satisfaction (R(2) = 0.26) more than any dimension-specific
      measure (R(2) from 0.05 to 0.17). Self-rated SA, vis-a-vis dimension-specific
      measures, was related to a different set of correlates, and was notably
      independent of chronological age, sex, education, socioeconomic status, and
      medical comorbidity, but was significantly related to ethnicity. CONCLUSION: The
      self-rated analogue scale is a sensitive global measure of SA encompassing a
      spectrum of underlying dimensions and subjective perspectives and its validity is
      well supported in this study.

PMID- 24119863
TI  - Long-term follow-up of patients with deferred coronary intervention guided by
      measurement of fractional flow reserve.
AB  - INTRODUCTION AND AIMS: The functional significance of coronary lesions can be
      assessed in the cardiac catheterization laboratory by determination of fractional
      flow reserve (FFR), thus overcoming one of the major limitations of conventional
      angiography. The aim of this study was to analyze the long-term clinical course
      of patients with intermediate coronary stenosis (50-70%) deferred for
      intervention based on FFR <0.80. METHODS: Between May 1999 and December 2009, 300
      lesions in 231 patients (mean age 65 +/- 10 years, 68% male and 75.3% with
      multivessel disease) were studied by FFR. Intervention was deferred in 282 (94%)
      lesions and 18 were treated based on FFR <0.80. We assessed the occurrence of
      major adverse cardiovascular events (MACE), defined as cardiovascular death, non
      fatal acute coronary syndrome and target lesion revascularization (TLR). RESULTS:
      During a median follow-up of 637 days (interquartile range 455-1160), there were
      15 (6.5%) MACE in the subgroup of patients with target lesion intervention
      deferred based on FFR: one cardiovascular death, four hospitalizations for acute
      coronary syndrome and 14 TLR (12 patients were treated percutaneously and two
      underwent coronary artery bypass grafting). MACE-free survival at one year follow
      up was 97.8%. CONCLUSION: These results, in a real-world population, support the
      current trend to base the decision to treat on functional rather than purely
      anatomical criteria, in order to improve safety and efficiency.

PMID- 24119864
TI  - Association between cardiovascular disease and socioeconomic level in Portugal.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of morbidity, mortality
      and disability in Portugal. Socioeconomic level is known to influence health
      status but there is scant evidence on socioeconomic inequalities in
      cardiovascular disease in Portugal. AIM: To analyze the distribution of
      cardiovascular disease in the Portuguese population according to socioeconomic
      status. METHODS: We conducted a cross-sectional study using data from the fourth
      National Health Survey on a representative sample of the Portuguese population.
      Socioeconomic inequalities in cardiovascular disease, risk factors and number of
      medical visits were analyzed using odds ratios according to socioeconomic status
      (household equivalent income) in the adult population (35-74 years). Comparisons
      focused on the top and bottom 50% and 10% of household income distribution.
      RESULTS: Of the 21 807 individuals included, 53.3% were female, and mean age was
      54 +/- 11 years. Cardiovascular disease, stroke, ischemic heart disease,
      hypertension, diabetes, obesity and physical inactivity were associated with
      lower socioeconomic status, while smoking was associated with higher status;
      number of medical visits and psychological distress showed no association. When
      present, inequality was greater at the extremes of income distribution.
      CONCLUSIONS: The results reveal an association between morbidity, lifestyle and
      socioeconomic status. They also suggest that besides improved access to effective
      medical intervention, there is a need for a comprehensive strategy for health
      promotion and disease prevention that takes account of individual, cultural and
      socioeconomic characteristics.

PMID- 24119865
TI  - Single coronary artery with mesocardia, situs inversus, and atrioventricular and
      ventriculoarterial discordance.

PMID- 24119866
TI  - Medical and surgical cardiology: reflections on the current treatment of severe
      aortic stenosis.

PMID- 24119867
TI  - Prognostic value of left atrial volume in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Increased left atrial (LA) size is a prognostic marker of mortality
      in the general population. LA size varies considerably in patients with dilated
      cardiomyopathy (DCM), but its clinical significance has not been widely studied.
      OBJECTIVE: To evaluate the long-term prognostic value of LA volume (LAV) in
      patients with DCM. METHODS: We prospectively studied patients admitted from
      January to December 2004 with a diagnosis of DCM, in sinus rhythm. Complete
      echocardiographic study at rest and after pharmacological stress was performed in
      all patients. The composite endpoint of mechanical ventricular assistance (MVA),
      heart transplantation or death during follow-up was assessed by univariate and
      multivariate analysis using a Cox regression model. RESULTS: The study population
      consisted of 35 patients (68.6% male, mean age 52.0) with DCM, 82.9% of non
      ischemic etiology. Ejection fraction (EF) at rest was 31.1 +/- 9.4%. During
      follow-up, eight patients died, one was placed on MVA and one underwent
      transplantation. Univariate Cox analysis showed various potential
      echocardiographic markers of prognosis in our population, including LA size in M
      mode (HR 1.12, CI: 0.99-1.26, p=0.067), LAV (HR 1.03, CI: 1.00-1.07, p=0.046),
      LAV adjusted for body surface area (HR 1.03, CI: 0.99-1.26, p=0.049), E/A ratio
      (HR 0.99; CI: 0.99-1.81; p=0.060); E/A >2 (HR 7.00, CI: 1.48-32.43, p=0.014) and
      mitral E/E' ratio (HR 1.04, CI: 1.00-1.09, p=0.074). The only variable that
      remained in the multivariate model was LAV, with a cut-off value of 63 ml (HR
      7.7, CI: 0.97-60.61, p=0.05). CONCLUSIONS: LAV was the only echocardiographic
      determinant of MVA, heart transplantation or death in our population with DCM.
      The echocardiographic parameters commonly used for risk stratification such as
      EF, left ventricular end-diastolic diameter and contractile reserve did not show
      prognostic significance in our study.

PMID- 24119868
TI  - The warning glove - development and evaluation of a multimodal action-specific
      warning prototype.
AB  - This paper has two objectives: first, to introduce the concept of multimodal
      action-specific warnings and its prototypic realization in the form of a warning
      glove and second, to present the main findings of a user study that was conducted
      to test the warning glove against a conventional warning system. Regarding the
      first goal, the combination of multimodality and action-specificity was
      implemented by attaching electronic actuators on a right-handed glove for
      transmitting visual, auditory and tactile feedback. For the second objective, a
      user study was conducted to test the hypothesis that the warning glove is capable
      of obtaining faster responses and to determine the perceptions of the users
      regarding the appropriateness of the warning glove. The results confirmed the
      assumption of faster response times and participants perceived the warning glove
      to be 'fairly appropriate'. These results warrant further development of this
      multimodal action-specific warning glove. 

PMID- 24119869
TI  - Novel coumarin-dihydropyrazole thio-ethanone derivatives: design, synthesis and
      anticancer activity.
AB  - A series novel 1-(3-substituted-5-phenyl-4,5-dihydropyrazol-1-yl)-2-thio-ethanone
      derivatives as potential telomerase inhibitors were designed and synthesized. The
      bioassays demonstrated that compounds 4a, 4f, 4j and 7b, 7d occupied high
      antiproliferative activity against SGC-7901, MGC-803, Bcap-37 and HEPG-2 cell
      lines. By a modified TRAP assay, some title compounds were tested against
      telomerase, and compound 4f showed the most potent inhibitory activity with IC50
      value at 0.92 +/- 0.09 MUM. The mechanism of antitumor action indicated that
      title compounds 4f and 7b could suppress cell proliferation through inducing cell
      cycle arrest in G0/G1 phase.

PMID- 24119870
TI  - Transferring brain-computer interfaces beyond the laboratory: successful
      application control for motor-disabled users.
AB  - OBJECTIVES: Brain-computer interfaces (BCIs) are no longer only used by healthy
      participants under controlled conditions in laboratory environments, but also by
      patients and end-users, controlling applications in their homes or clinics,
      without the BCI experts around. But are the technology and the field mature
      enough for this? Especially the successful operation of applications - like text
      entry systems or assistive mobility devices such as tele-presence robots -
      requires a good level of BCI control. How much training is needed to achieve such
      a level? Is it possible to train naive end-users in 10 days to successfully
      control such applications? MATERIALS AND METHODS: In this work, we report our
      experiences of training 24 motor-disabled participants at rehabilitation clinics
      or at the end-users' homes, without BCI experts present. We also share the
      lessons that we have learned through transferring BCI technologies from the lab
      to the user's home or clinics. RESULTS: The most important outcome is that 50% of
      the participants achieved good BCI performance and could successfully control the
      applications (tele-presence robot and text-entry system). In the case of the tele
      presence robot the participants achieved an average performance ratio of 0.87
      (max. 0.97) and for the text entry application a mean of 0.93 (max. 1.0). The
      lessons learned and the gathered user feedback range from pure BCI problems
      (technical and handling), to common communication issues among the different
      people involved, and issues encountered while controlling the applications.
      CONCLUSION: The points raised in this paper are very widely applicable and we
      anticipate that they might be faced similarly by other groups, if they move on to
      bringing the BCI technology to the end-user, to home environments and towards
      application prototype control.

PMID- 24119871
TI  - Detection of cytokeratins in ghost cells of calcifying cystic odontogenic tumor
      indicates an altered keratinization and hair follicle differentiation for their
      development.
AB  - Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of
      odontogenic origin characterized by an ameloblastoma-like epithelium and the
      presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck)
      expression on these lesions remains unclear and needs to be clarified. To this
      end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining
      of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the
      epithelium lining was divided into 3 distinct regions: basal layer, suprabasal
      layer, and the compartment composed of ghost cells. In this study, 6 cases
      (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were
      negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost
      cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was
      found in the basal and suprabasal layers, including the ghost cells. The results
      showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT
      as being of odontogenic origin, and the restricted expression of Ck6 in the ghost
      cells may be indicative that these cells suffer an altered differentiation into
      hair follicles in CCOTs.

PMID- 24119872
TI  - Posttraumatic pulsating exophthalmos in a child.

PMID- 24119873
TI  - Atopic dermatitis: looking beyond the skin.

PMID- 24119874
TI  - Acute infantile dacryoadenitis.

PMID- 24119875
TI  - Chronic spinal epidural hematoma.

PMID- 24119876
TI  - AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: a
      whole-hemisphere autoradiography study.
AB  - Dysfunction of the brain glutamate system has been associated with alcoholism.
      Ionotropic glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      receptors (AMPARs) play an important role in both neurotransmission and post
      synaptic plasticity. Alterations in AMPAR densities may also play a role in the
      neurobiological changes associated with alcoholism. In the present study, [(3)H]
      AMPA binding density was evaluated in the nucleus accumbens (NAc), frontal
      cortex, anterior cingulate cortex (ACC), dentate gyrus and hippocampus of
      Cloninger type 1 (n=9) and 2 (n=8) alcoholics, and compared with non-alcoholic
      control subjects (n=10) by post-mortem whole-hemisphere autoradiography. The
      [(3)H] AMPA binding density was significantly higher in the ACC of early onset
      type 2 alcoholics when compared with controls (p=0.011). There was also a
      significant negative correlation between [(3)H] AMPA binding and previously
      published results of dopamine transporter (DAT) density in the ACC in these same
      brain samples (R=-0.95, p=0.001). Although preliminary, and from a relatively
      small diagnostic group, the present results help to further explain the pathology
      of alcohol dependence and impulsive behaviour in type 2 alcoholics. 

PMID- 24119877
TI  - [HNF1B-related disease: paradigm of a developmental gene and unexpected
      recognition of a new renal disease].
AB  - HNF1B encodes for a transcription factor involved in the early development of the
      kidney, pancreas, liver and genital tract. Mutations in HNF1B are dominantly
      inherited and consist of whole-gene deletion, or small mutation. De novo mutation
      occurs in half of tested kindreds. HNF1B-related disease combines renal and non
      renal manifestations. Renal involvement is heterogeneous and may escape early
      recognition. During fetal life and childhood, it mostly consists of
      hyperechogenic kidneys or bilateral renal cystic hypodysplasia. The adult
      phenotype encompasses tubulointerstitial profile at presentation and slowly
      progressive renal decline (-2 ml/min/year). Renal involvement includes renal
      cysts (mostly few cortical cysts), a solitary kidney, pelvi-caliceal
      abnormalities, hypokalemia and hypomagnesemia related to tubular leak, and more
      rarely, Fanconi syndrome and chromophobe renal carcinoma. The latter warrants
      ultrasound screening. Extrarenal phenotype consists of diabetes mellitus (MODY
      5), exocrine pancreas failure and pancreas atrophy; fluctuation liver tests
      abnormalities; diverse genital tract abnormalities in females or infertility in
      males; and mild mental retardation in rare individuals. Phenotype heterogeneity
      within families is striking. Individuals progressing to end-stage renal disease
      are eligible for kidney transplantation (or combined pancreas and kidney
      transplantation for diabetic individuals). While HNF1B disease was still unknown
      one decade ago, it has emerged as the second most prevalent dominantly inherited
      kidney disease. Data available pave the way for early recognition and improved
      specific management, including genetic counselling.

PMID- 24119878
TI  - Electrocardiographic abnormalities in the first year after heart transplantation.
AB  - STUDY AIM: Describe ECG abnormalities in the first year following transplant
      surgery. METHODS: Analysis of 12-lead ECGs from heart transplant subjects
      enrolled in an ongoing multicenter clinical trial. RESULTS: 585 ECGs from 98
      subjects showed few with abnormal cardiac rhythm (99% of ECGs were sinus
      rhythm/tachycardia). A majority of subjects (69%) had either right
      intraventricular conduction delay (56%) or right bundle branch block (13%). A
      second prevalent ECG abnormality was atrial enlargement (64% of subjects) that
      was more commonly left atrial (55%) than right (30%). CONCLUSIONS: Right
      intraventricular conduction delay or right bundle branch block is prevalent in
      heart transplant recipients in the first year following transplant surgery.
      Whether this abnormality is related to acute allograph rejection or
      endomyocardial biopsy procedures is the subject of the ongoing clinical trial.
      Atrial enlargement ECG criteria (especially, left atrial) are also common and are
      likely due to transplant surgery with subsequent atrial remodeling.

PMID- 24119879
TI  - Posterior lumbar interbody fusion for aged patients with degenerative
      spondylolisthesis: is intentional surgical reduction essential?
AB  - BACKGROUND CONTEXT: Surgical reduction and posterior lumbar interbody fusion
      (PLIF) is commonly used to recover segmental imbalance in degenerative
      spondylolisthesis. However, whether intentional reduction of the slipped vertebra
      during PLIF is essential in aged patients with degenerative spondylolisthesis
      remains controversial. PURPOSE: We compared the outcomes of surgical reduction
      and fusion in situ among aged patients who underwent PLIF for degenerative
      spondylolisthesis. STUDY DESIGN: A prospective randomized clinical trial on the
      surgical treatment of degenerative spondylolisthesis patients aged older than 70
      years. PATIENT SAMPLE: Between January 2006 and December 2009, 73 patients aged
      70 years or older with single-level degenerative spondylolisthesis requiring
      surgical treatment were included in this study. OUTCOME MEASURES: Clinical
      outcomes were assessed using the visual analog scale, Oswestry Disability Index,
      and Japanese Orthopedic Association scores. Radiographic outcomes included
      percentage of vertebral slippage, focal lordosis, and disc height. METHODS: The
      73 patients were randomly assigned to two groups treated using surgical reduction
      (Group A, n=36) and fusion in situ (Group B, n=37). Both groups were followed up
      for an average of 33.2 months (range, 24-54 months). The clinical and
      radiographic outcomes were compared between the two groups. RESULTS: Surgical
      complications were similar in the two groups. The average operative time and
      blood loss during surgery did not insignificantly differ (p>.05) between the two
      groups. Spondylolisthesis, disc height, and focal lordosis were significantly
      improved postoperatively in both groups. There was no obvious difference in
      clinical outcomes, as assessed using the visual analog scale, Oswestry Disability
      Index, and Japanese Orthopedic Association scores, although the radiographic
      outcomes were considerably better in Group A than in Group B. CONCLUSIONS:
      Posterior lumbar interbody fusion with pedicle screws fixation, with or without
      intraoperative reduction, provides good outcomes in the surgical treatment of
      aged patients with degenerative spondylolisthesis. Better radiological outcomes
      by intentional reduction do not necessarily indicate better clinical outcomes.

PMID- 24119880
TI  - Complete debridement for treatment of thoracolumbar spinal tuberculosis: a
      clinical curative effect observation.
AB  - BACKGROUND CONTEXT: Traditional focal debridement involves clearing of cold
      abscesses, caseous necrosis, residual intervertebral disc tissue, sinus tracts,
      bony sequestration, and inflammatory granulation. Reports have demonstrated that
      approximately 13% to 26% of patients were not better or relapsed after
      traditional focal debridement; these patients required a second surgery or
      prolonged antituberculous therapy. The presence of retained and diseased focal
      tissues requiring removal remains poorly understood. The contents of these
      retained tuberculous foci, improvement of surgical strategies, and improvement in
      spinal tuberculosis success rate are key subjects for discussion. PURPOSE: To
      explain the contents of foci and explore the surgical methods and curative effect
      of complete debridement. STUDY DESIGN: Retrospective study of the curative effect
      of treatment of thoracolumbar spinal tuberculosis by using complete debridement.
      PATIENT SAMPLE: A total of 289 patients were included. OUTCOME MEASUREMENT: The
      outcomes were evaluated clinically by Frankel grading. The status of the anterior
      fusion was assessed according to the Moon standard. Eradication of infection was
      determined by the level of C-reactive protein and erythrocyte sedimentation rate.
      X-ray, computed tomography, and magnetic resonance imaging were used to evaluate
      disease localization and morphology. METHODS: A total of 289 patients with spinal
      tuberculosis (150 male and 139 female patients, aged 18-82; average age, 41.0+/
      1.4 years) were included in this study. Damage to the vertebrae was as follows:
      86 patients had thoracic damage, 49 had thoracolumbar damage, 125 had lumbar
      damage, and 47 had lumbosacral segment damage. After 2 to 4 weeks of
      antituberculous therapy, all patients underwent anterior debridement, deformity
      correction, graft fusion, and internal fixation. In this study, complete
      debridement was defined as the clearing of any damage or disease, including psoas
      abscesses, granulomas, residual intervertebral disc tissue, sinus tracts, bony
      sequestration, and inflammatory granulation. Tuberculosis cavities, sclerotic
      walls, and bony bridges that had no support and that were eroded by the foci were
      also removed. A total of 108 patients underwent anterior fixation with the Zephir
      system (Medtronic Sofamor-Danek, Minneapolis, MN, USA), Z plates (Medtronic
      Sofamor-Danek), or Ventrifix (China Great Wall Corporation, Beijing, China). A
      total of 181 patients underwent fixation, posterior correction, and one or two
      second anterior debridements and graft fusions. Posterior fixation, including
      TSRH (Medtronic Sofamor-Danek), Cotrell-Dubousset (Medtronic Sofamor-Danek),
      General Spinal System (WeiGao Orthopaedic Devices Company, Weihai City, China),
      or UPASS (WeiGao Orthopaedic Devices Company), was performed. All patients
      underwent structural bone grafting, including autologous iliac bone (251
      patients), titanium mesh (32 patients), and rib (6 patients). RESULTS: The 289
      patients were followed for 72.0+/-2.8 months, with 265 patients (91.69%)
      completely treated and 24 incompletely treated, including 3 who suspended
      chemotherapy because of liver or renal failure. Twenty-one patients (7.27%)
      failed to have a complete debridement, including 16 with incomplete bone
      debridement, 6 of whom underwent a second surgery, and 10 who received
      conservative therapy; 5 of this group had incomplete abscess debridement, 3
      underwent a second surgery, and 2 received puncture aspiration of abscess under
      computed tomographic guidance; the second surgery rate was 3.81%. Twenty-two
      patients had surgery complications, including three with graft displacement, five
      with wound infection and fat liquefaction, four with pleural effusion, six with
      pain at the graft harvesting site, and four with incisional hernia. Bone graft
      healing was observed 4.3+/-1.2 months after surgery. The Cobb angle before and
      after surgery and at the final follow-up was 22.16+/-11.51 degrees , 8.11+/-4.83
      degrees , and 9.96+/-3.49 degrees , respectively, with a mean correction of
      63.40% after surgery; however, a 1.85+/-1.34 degrees  loss was observed at the
      final follow-up with loss rate of 8.35%. CONCLUSIONS: Sclerotic bone, multiple
      cavities, and bony bridges are foci in spinal tuberculosis. Clearing tuberculous
      foci, sclerotic bone, multiple cavities, and bony bridges to increase the
      curative effect is an effective treatment method.

PMID- 24119881
TI  - Diagnosis and treatment of vertebral hemangiomas with neurologic deficit: a
      report of 29 cases and literature review.
AB  - BACKGROUND CONTEXT: Vertebral hemangiomas (VHs) are called benign tumors but are
      actually just vascular malformations. The diagnosis and treatment for aggressive
      VHs is still controversial, due to their rarity. PURPOSE: To evaluate the safety
      and efficiency of the present diagnostic methods and treatment choices. STUDY
      DESIGN: A retrospective study of aggressive VHs with neurologic deficit. PATIENTS
      SAMPLE: A total of 29 consecutive aggressive VH cases were diagnosed and treated
      in our department since 2001. OUTCOME MEASURES: We routinely took anteroposterior
      and lateral spinal roentgenograms, computed tomography, and magnetic resonance
      images. METHODS: Trocar biopsy is indicated in suspected malignant cases.
      Radiotherapy was usually our first choice if the neurologic deficit was mild or
      developed slowly. Surgery was indicated if the neurologic deficit was severe or
      developed quickly or if the radiotherapy was not effective. RESULTS: This series
      included 12 males and 17 females, and the mean age at diagnosis was 44.0 years
      (range, 21-72 years). Ten patients had radiculopathy, 1 had cauda equina
      syndrome, and 18 cases had myelopathy. Twenty-one cases had lesions in the
      thoracic spine, 5 in the lumbar, and 3 in the cervical region. Eleven cases had
      untypical image findings, including five cases with pathologic vertebral
      fracture. The neurologic compression came from only epidural soft tumor mass in
      18 cases, whereas it came from both bony compression and soft lesion in the other
      11 cases. Ten cases had radiotherapy alone, but two failed and had surgery later.
      Twenty-one cases had surgery. In the 12 cases having surgical decompression
      without vertebroplasty, the average estimated blood loss was 1900 mL, and it was
      1093 mL for the eight cases having decompression with vertebroplasty. The average
      follow-up was 51.1 months (range, 24-133 months). There was no recurrence in
      those cases with radiotherapy, whereas three had local recurrence in those six
      cases treated by surgical decompression alone without radiotherapy. CONCLUSIONS:
      In aggressive VHs, epidural soft-tissue compression was usually the main reason
      for neurologic deficit. In cases with rapid progressive and/or severe myelopathy,
      posterior decompression and stabilization could be combined with intraoperative
      vertebroplasty to reduce blood loss.

PMID- 24119882
TI  - Vertebral arteriovenous fistula following C2 pedicle screw fixation.

PMID- 24119883
TI  - Suspected lumbar compartment syndrome: a rare cause of low back pain after
      strenuous exercise.

PMID- 24119884
TI  - Pancreas-sparing duodenectomy for gastrointestinal stromal tumor.
AB  - BACKGROUND: Pancreas-sparing duodenectomy (PSD) is a promising alternative
      procedure to pancreaticoduodenectomy for the treatment of duodenal tumors with
      low-grade malignant behavior. METHODS: Between March 2003 and September 2012, PSD
      was performed in 7 patients with a gastrointestinal stromal tumor (GIST) in the
      second (n = 5) or third (n = 2) portions of the duodenum. The short- and long
      term outcomes of treatment were analyzed in all patients. RESULTS: The median
      blood loss was 160 mL, and the median operative time was 315 minutes. No
      pancreatic leakage or perioperative mortality occurred. Surgical margins were
      negative in all cases. All patients were alive at the median follow-up time of 42
      months after PSD. The recurrence-free 5-year survival rate was 53% in all
      patients. Hepatic metastases developed in 2 of the 5 patients with high- or
      intermediate-grade risks at the time of diagnosis. Hepatic resection was
      performed, and imatinib mesylate was administered in the 2 cases. CONCLUSIONS:
      Good short- and long-term outcomes and surgical curability were observed in
      patients treated with PSD for duodenal GIST.

PMID- 24119885
TI  - Readmission after delayed diagnosis of surgical site infection: a focus on
      prevention using the American College of Surgeons National Surgical Quality
      Improvement Program.
AB  - BACKGROUND: Surgical site infection (SSI) is a costly complication leading to
      increased resource use and patient morbidity. We hypothesized that postdischarge
      SSI results in a high rate of preventable readmissions. METHODS: We used our
      institutional American College of Surgeons National Surgical Quality Improvement
      Program database to identify patients undergoing general surgery procedures from
      2006 to 2011. RESULTS: SSIs developed in 10% of the 3,663 patients who underwent
      an inpatient general surgical procedure. SSI was diagnosed after discharge in 48%
      of patients. Patients with a diagnosis of SSI after discharge were less likely to
      have a history of smoking (15% vs 28%, P = .001), chronic obstructive pulmonary
      disease (3% vs 9%, P = .015), congestive heart failure (0% vs 3%, P = .03), or
      sepsis within 48 hours preoperatively (17% vs 32%, P = .001) compared with
      patients diagnosed before discharge. Over 50% of the patients diagnosed with SSI
      after discharge required readmission. CONCLUSIONS: A diagnosis of SSI after
      discharge is associated with a high readmission rate despite occurring in
      healthier patients. We propose discharge teaching improvements and a wound
      surveillance clinic within the first week may result in a decreased readmission
      rate.

PMID- 24119886
TI  - Is magnetic resonance imaging in addition to a computed tomographic scan
      necessary to identify clinically significant cervical spine injuries in obtunded
      blunt trauma patients?
AB  - BACKGROUND: Guidelines are in place directing the clearance of the cervical spine
      in patients who are awake, alert, and oriented, but a gold standard has not been
      recognized for patients who are obtunded. Our study is designed to determine if
      magnetic resonance imaging (MRI) detects clinically significant injuries not seen
      on computed tomographic (CT) scans. METHODS: The trauma registry was used to
      identify and retrospectively review medical records of blunt trauma patients from
      January 1, 2005, to March 30, 2012. Only obtunded patients with a CT scan and MRI
      of the cervical spine were included. RESULTS: The study cohort consisted of 277
      patients. In 13 (5%) patients, MRI detected clinically significant cervical spine
      injuries that were missed by CT scans, and in 7 (3%) these injuries required
      intervention. The number needed to screen with MRI to prevent 1 missed injury was
      21. CONCLUSIONS: The findings suggest that the routine use of MRI in clearing the
      cervical spine in the obtunded blunt trauma patient.

PMID- 24119887
TI  - Enhanced postoperative recovery pathways in emergency surgery: a randomised
      controlled clinical trial.
AB  - BACKGROUND: Enhanced recovery pathways are now widely used in elective surgical
      procedures. The feasibility of enhanced postoperative recovery pathways in
      emergency surgery for perforated peptic ulcer disease was investigated in this
      randomized controlled clinical trial. METHODS: Patients with perforated peptic
      ulcer disease who underwent laparoscopic repair were randomized into 2 groups.
      Group 1 patients were managed with standard postoperative care and group 2
      patients with enhanced postoperative recovery pathways. The primary endpoints
      were the length of hospital stay and morbidity and mortality. RESULTS: Forty
      seven patients were included in the study. There were 26 patients in group 1 and
      21 in group 2. There were no significant differences in the morbidity and
      mortality rates, whereas the length of hospital stay was significantly shorter in
      group 2. CONCLUSIONS: The application of enhanced postoperative recovery pathways
      in selected patients with perforated peptic ulcer disease who undergo
      laparoscopic Graham patch repair seems feasible.

PMID- 24119888
TI  - Surgical resection of carotid body paragangliomas: 10 years of experience.
AB  - BACKGROUND: Carotid body tumors (CBTs) are relatively rare neoplasms, and even if
      they are considered predominantly benign, there is an indication for early
      surgical removal. The objective of this study was to conduct a review of the
      surgical management of CBTs. METHODS: A retrospective study identified 34 cases
      (12 men and 19 women) of tumors in patients who had undergone surgical resection
      of pathologically confirmed CBTs over a period of 10 years from 2001 to 2011 in 2
      academic departments of general surgery in Italy. RESULTS: In our series, 10 CBTs
      (31%) were Shamblin class I, 13 (41%) were class II, and 9 tumors (27%) were
      class III. Two patients (6%) had transient cerebral ischemia immediately after
      operation. One patient (3%) died of postoperative cerebral ischemia after surgery
      for internal carotid artery thrombosis. CONCLUSIONS: The experience of this
      casuistry shows that the procedure is relatively low risk for Shamblin I and II
      classes, whereas there is an increasing risk of neurovascular complications for
      Shamblin III class.

PMID- 24119889
TI  - Fatal gunshot wound to the head: the impact of aggressive management.
AB  - BACKGROUND: Patients with fatal gunshot wounds (GSWs) to the head often have poor
      outcomes but are ideal candidates for organ donation. The purpose of this study
      was to evaluate the effects of aggressive management on organ donation in patient
      with fatal GSWs to the head. METHODS: A 5-year review of all patients at a trauma
      center with GSWs to the head was performed. The primary outcome was organ
      donation after fatal GSW to the head. RESULTS: A total of 98 patients with fatal
      GSWs to the head were identified. The rate of potential organ donation was 70%,
      of whom 49% eventually donated 72 solid organs. Twenty-five percent of patients
      were not considered eligible for donation as a result of disseminated
      intravascular coagulopathy. The T4 protocol lead to significant organ procurement
      rates (odds ratio, 3.6; 95% confidence interval, 1.3 to 9.6; P = .01). Failures
      to organ donation in eligible patients were due to lack of family consent and
      cardiac arrest. CONCLUSIONS: Organ donation after fatal GSW to the head is a
      legitimate goal. Management goals should focus on early aggressive resuscitation
      and correction of coagulopathy.

PMID- 24119890
TI  - Hand-assisted laparoscopic surgery versus open surgery for colorectal disease: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Laparoscopic colorectal surgery remains one of the most challenging
      techniques to learn. METHODS: The authors collected studies that have compared
      hand-assisted laparoscopic surgery (HALS) and open surgery for the treatment of
      colorectal disease over the past 17 years. Data of interest for HALS and open
      surgery were subjected to meta-analysis. RESULTS: Twelve studies that included
      1,362 patients were studied. In total, 2.66% of HALS procedures were converted to
      laparotomy. Compared with the open surgery group, blood loss, rate of wound
      infection, and ileus in the HALS group decreased, and incision length, recovery
      of gastrointestinal function, and hospitalization period were shorter. There were
      no significant differences in operating time, hospitalization costs, mortality,
      and complications, including urinary tract infection, pneumonia, and anastomotic
      leak, between the groups. CONCLUSIONS: HALS has the advantages of minimal
      invasion, lower blood loss, shorter incision length, and faster recovery, and it
      can shorten the length of hospitalization without an increase in costs. The
      drawbacks are that a small number of patients who undergo HALS may need to be
      converted to laparotomy, and the oncologic safety and long-term prognosis are not
      clear.

PMID- 24119891
TI  - Laterality of central venous sampling: lack of effect on the accuracy of
      intraoperative parathyroid hormone monitoring.
AB  - BACKGROUND: The purpose of this study was to determine if laterality of internal
      jugular vein (IJV) sampling affects the accuracy of intraoperative parathyroid
      hormone (PTH) monitoring during parathyroidectomy for primary
      hyperparathyroidism. METHODS: In this study, 109 patients underwent
      parathyroidectomy (82 with unilateral disease, 27 with multigland disease). PTH
      samples were taken from both the left and the right IJV at these time points:
      preincision (baseline) and then at 5, 10, and, in selected patients, 20 minutes
      after excision. The Miami criterion was used to determine operative success.
      RESULTS: In all 109 patients combined, the mean decreases in intraoperative PTH
      levels were 73.8 +/- 22.2% for the left IJV and 71.9 +/- 23.0% for the right IJV
      (P = .22). The Miami criterion was met in 105 patients: in 100 (95%) left IJV
      samples and 99 (94%) right IJV samples (P = 1.00). CONCLUSIONS: No difference was
      found in the accuracy of intraoperative PTH monitoring between patients' left and
      right IJV samples. Central venous laterality did not affect fulfillment of the
      Miami criterion.

PMID- 24119893
TI  - Simple frailty score predicts postoperative complications across surgical
      specialties.

PMID- 24119892
TI  - Cognitive function after bariatric surgery: evidence for improvement 3 years
      after surgery.
AB  - BACKGROUND: Bariatric surgery is associated with improved cognition, and it is
      possible that such improvements are found at extended follow-ups. We hypothesized
      that cognitive improvement would be maintained 3 years after bariatric surgery.
      METHODS: Fifty bariatric patients were recruited from the Longitudinal Assessment
      of Bariatric Surgery parent project. Participants completed a computerized
      cognitive test battery to assess cognitive function at 12 weeks, 12 months, 24
      months, and 36 months after surgery. RESULTS: Repeated measures revealed main
      effects for attention, executive function, and memory. Attention improved up to
      24 months and then slightly declined although it still fell within the average
      range at 36 months. Improvements in executive function reached their peak at 36
      months after surgery. Short-term improvements in memory were maintained at 36
      months. No main effect emerged for language. CONCLUSIONS: Bariatric surgery may
      lead to lasting improvements in cognition. Prospective studies with extended
      follow-ups (eg, 10 years) should examine whether bariatric surgery can attenuate
      cognitive decline in severely obese patients.

PMID- 24119894
TI  - Anatomical causes of female infertility and their management.
AB  - The main female anatomical causes of infertility include post-infectious tubal
      damage, endometriosis, and congenital/acquired uterine anomalies. Congenital
      (septate uterus) and acquired (myomas and synechiae) diseases of the uterus may
      lead to infertility, pregnancy loss, and other obstetric complications. Pelvic
      inflammatory disease represents the most common cause of tubal damage. Surgery
      still remains an important option for tubal factor infertility, with results in
      terms of reproductive outcome that compare favorably with those of in vitro
      fertilization. Endometriosis is a common gynecologic condition affecting women of
      reproductive age, which can cause pain and infertility. The cause of infertility
      associated with endometriosis remains elusive, suggesting a multifactorial
      mechanism involving immunologic, genetic, and environmental factors. Despite the
      high prevalence of endometriosis, the exact mechanisms of its pathogenesis are
      unknown. Specific combinations of medical, surgical, and psychological treatments
      can ameliorate the quality of life of women with endometriosis. In the majority
      of cases, surgical treatment of endometriosis has promoted significant increases
      in fertilization rates. There are obvious associations between endometriosis and
      the immune system, and future strategies to treat endometriosis might be based on
      immunologic concepts. 

PMID- 24119895
TI  - Effects of vaginal discharge on female sexual function.
AB  - OBJECTIVE: To assess the effects of vaginal discharge on female sexual
      dysfunction (FSD) by using the Female Sexual Function Index (FSFI). METHODS: In a
      study at a university hospital in Canakkale, Turkey, women affected by vaginal
      discharge and age-matched healthy control women were recruited between January
      and December 2012. Women were grouped in accordance with their vaginal discharge
      complaints and each participant completed the FSFI questionnaire. RESULTS: A
      total of 114 women were included in the study. Women in the first group (n=58)
      had no vaginal discharge or had physiologic vaginal discharge, those in the
      second group (n=29) had abnormal vaginal discharge with itching, and those in the
      third group (n=27) had abnormal vaginal discharge without itching. Compared with
      the first group, women in the second and third groups had higher FSFI scores for
      desire, arousal, orgasm, and pain, in addition to higher overall FSFI scores.
      Women with genital malodor had significantly higher FSFI scores than patients
      without genital malodor (23.83 +/- 5.07 vs 21.15 +/- 4.78; P=0.008). CONCLUSION:
      Women with abnormal vaginal discharges were found to have better FSFI scores for
      some domains. This finding may be attributed to the adverse effects of sexual
      intercourse on vaginal infections.

PMID- 24119897
TI  - [Hot spots in cancer immunotherapy and status quo of vaccine research for lung
      cancer].

PMID- 24119896
TI  - Immunodetection of cells with a CD44+/CD24- phenotype in canine mammary
      neoplasms.
AB  - BACKGROUND: Cancer stem cells (CSCs) are able to self-renew and to form
      metastases. Using flow cytometry, CSCs were detected in canine mammary tumors as
      cells CD44(+) and CD24(-). The aim of this study was to detect these CSCs by
      immunohistochemistry and correlate their frequency with canine mammary neoplasm
      grade and histopathological type.130 mammary neoplasm samples were selected from
      tissue blocks at the Department of Pathology at UNESP and classified according to
      (BJVP 4:153-180, 2011). These samples were composed by adenomas, lymph node
      metastases, solid carcinomas grades II and III, tubular, papillary and carcinomas
      in mixed tumor grades I, II and III. Immunohistochemistry was performed with
      antibodies against CD44 and CD24. Linear regression was performed using Pearson's
      correlation test. RESULTS: The value at CD44 was positive and CD24 becomes zero
      was 46.75%. Cells with a CD44(+)/CD24(-) phenotype were detected in 40 out of 130
      samples with an advantage of high grade tumors (II and III) and metastases among
      tubular, papillary and carcinomas in mixed tumors. In these samples, percentages
      of cells stained by CD44 and CD24 antibodies were 62.2% and 0%, respectively.
      Published reports usually correlate grade III tumors with the expression of CD44
      but not with CD24 expression. Studies using flow cytometry have found CSC
      frequencies similar to those found in our study. CONCLUSIONS:
      Immunohistochemistry was found to be a reliable technique for the detection of
      CSCs in canine mammary neoplasms, and the frequency of these cells positively
      correlates with grades II and III tumors (poor prognosis).

PMID- 24119898
TI  - [CpG methyltransferase induced down-regulation of claudin-7, -8 and its effects
      on proliferation and apoptosis of human colorectal cancer HT-29 cells].
AB  - OBJECTIVE: To explore the regulatory effect of CpG methyltransferase (M.SssI) on
      expression of claudin-7 and claudin-8, promoting apoptosis and inhibiting
      proliferation of human colorectal cancer HT-29 cells. METHODS: HT-29 cells were
      treated with M.SssI (50 U/ml) for 24 hours. The methylation status of claudin-7
      and claudin-8 gene promoters was assayed by bisulfite sequencing PCR (BSP). Real
      time PCR with SYBR green I technique was used to detect the relative expression
      of claudin-7 and -8 mRNA, and claudin-7 and claudin-8 proteins were tested by
      cell immunofluorescence and Western blotting, while the effect on cell apoptosis
      was assessed by Hoechst 33342 fluorescence and flow cytometry. Inhibition of cell
      proliferation was measured by MTT assay. RESULTS: The amounts of methylated
      claudin-7 and claudin-8 gene CpGs were 25, 10 in the M.SssI group, 9 and 5 in the
      PBS group, 0 and 3 in the 5-azacytidine group, respectively. Compared with the
      PBS group, Claudin-7 and -8 were significantly reduced by M.SssI (P < 0.05), but
      increased by 5-azacytidine (P < 0.05) at both mRNA and protein levels. Hoechst
      33342 staining revealed that HT-29 cells treated with PBS and 5-azacytidine were
      not significantly different, showing even blue fluorescence, round shape and same
      cell volume. But the M.SssI group presented more apoptotic cells with intensive
      white fluorescence intensity. Cytometry indicated that early apoptotic index of
      the M.SssI group was increased by 84.7%, compared with that of the PBS group (P =
      0.002). Measurement of MTT optical density demonstrated that cell growth of the
      M.SssI group was significantly lower than that of the PBS group (P = 0.002), with
      an inhibition rate of 32.1%, whereas the proliferation of 5-azacytidine group was
      similar to that of the PBS group (P = 0.084). CONCLUSIONS: Our findings suggest
      that M.SssI can down-regulate claudin-7, -8 mRNA and proteins in the human colon
      cancer HT-29 cells by up-regulating methylation status of claudin-7 and -8 gene
      promoters, and finally induce apoptosis and inhibit proliferation of the tumor
      cells.

PMID- 24119899
TI  - [Double-mutated oncolytic adenovirus combined with gemcitabine for treating an
      orthotopic nude mouse model of bladder cancer].
AB  - OBJECTIVE: To investigate the therapeutic efficacy of double-mutated oncolytic
      adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer
      in an orthotopic nude mouse model. METHODS: The susceptibility to the adenovirus
      was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal
      cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with
      5-bromo-4-chloro-3-indolyl-beta-galactoside (X-Gal). Immunostaining against
      adenoviral hexon protein was performed to determine the selective replication of
      AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1
      cells in S phase of cell cycle after adenovirus infection. Cell viability after
      AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder
      cancer model was established in nude mice, and the inhibitory efficacy of
      intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed.
      RESULTS: Gene transduction efficiency was different among the cell lines, and
      correlated with expression of CAR. 5637 and KK47 cells with high expression of
      CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with
      little CAR expression were resistant to adenoviral infection. Immunostaining
      showed that the expression levels of hexon protein varied among the cell lines.
      Normal cells infected with AxdAdB-3 expressed little hexon protein. The
      proportion of S-phase cells was (39 +/- 3) % and (49 +/- 5) % in the AxCAlacZ-
      and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively
      induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with
      gemcitabine significantly inhibited the growth of bladder cancer cell lines. In
      vivo, the mean weight of the bladder tumors in mice treated with intravesical
      instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were
      400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and
      gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the
      combination therapy reduced tumors more effectively than either AxdAdB-3 (P <
      0.0001) or gemcitabine (P < 0.0001) alone. CONCLUSIONS: Intravesical instillation
      therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the
      orthotopic bladder cancer in nude mouse, and further relevant clinical studies
      are guaranteed.

PMID- 24119900
TI  - [Correlation between the methylation of SULF2 and WRN promoter and
      chemosensitivity to irinotecan in gastric cancer].
AB  - OBJECTIVE: To explore the relationship between SULF2 and WRN promoter methylation
      and chemosensitivity to irinotecan, and also the clinicopathological features in
      patients with gastric cancer. METHODS: The chemosensitivity to irinotecan was
      tested by MTT assay. The methylation of SULF2 and WRN promoter in the fresh
      gastric cancer tissues was detected by methylation specific PCR. The differences
      of chemosensitivity and clinicopathological features of the methylation group
      were compared with that of the non-methylation group. The tumor growth in nude
      mice bearing human gastric cancer xenografts treated with CPT-11was also
      observed. RESULTS: The methylation rates of SULF2 and WRN were 28.4% (29/102) and
      23.5% (24/102), respectively. There were no significant association between
      promoter methylation and clinicopathological features of patients including age,
      gender, histologic type, lymphatic invasion, and TNM Stage. In all the 102 cases,
      there were 30 cases of irrinotecan-sensitive group, and 72 cases of the
      irrinotecan-resistant group. The SULF2 methylation rate was 46.7% (14/30)in the
      sensitive group, and 20.8% (15/72) in the resistant group (P = 0.008),The WRN
      methylation rate was 33.3% (10/30) in the sensitive group, and 19.4% (14/72) in
      the resistant group (P = 0.214). Gastric cancer tissues were more sensitive to
      irrinotecan when both the genes were methylated. The nude mice bearing human
      gastric cancer xenografts with SULF2 methylation were more sensitive to
      irrinotecan. CONCLUSIONS: The detection of SULF2 and WRN promoter methylation may
      provide evidence for screening and targeting the most sensitive gastric cancer
      subpopulation suitable for personalized irrinotecan chemotherapy.

PMID- 24119901
TI  - [Establishment of an aromatase inhibitor letrozole-resistant breast cancer cell
      model].
AB  - OBJECTIVE: To establish a human breast cancer MCF-7 cell model stably
      overexpressing the aromatase gene (MCF-7-aromatase) and aromatase inhibitor
      letrozole-resistant MCF-7 cell model (MCF-7-LR). METHODS: We utilized the
      lentivirus-mediated gene transfer approach to establish MCF-7-aromatase cell and
      MCF-7 cell model stably overexpressing green fluorescent protein (GFP) (MCF-7
      GFP). The expression of aromatase in the MCF-7-aromatase and MCF-7-GFP cells was
      determined by reverse transcription polymerase chain reaction (RT-PCR), real time
      quantitative PCR (RT-qPCR), Western blot and immunoprecipitation (IP) assay. The
      proliferative ability in vitro of MCF-7-aromatase and MCF-7-GFP cells treated
      with testostorone and beta-estradiol (E2) was determined by WST-1 cell
      proliferation assay. The proliferative ability of MCF-7-aromatase cells treated
      with letrozole was determined by WST-1 assay. The half maximal inhibitory
      concentration (IC50 value) for letrozole was calculated from the nonlinear
      regression line of the plot of cell viability (percentage of control) versus
      letrozole concentration using Graphpad Prism software. MCF-7-aromatase cells were
      continuously cultured in the presence of testosterone and letrozole, thus
      letrozole-resistant MCF-7-LR cells were obtained. WST-1 assay was performed to
      determine their chemoresistance to letrozole. RESULTS: RT-PCR and RT-qPCR results
      revealed that the mRNA expression of aromatase was significantly increased in the
      MCF-7-aromatase cells compared with that in the MCF-7-GFP cells. Both Western
      blot and IP assays showed that the expression of aromatase protein was
      drastically increased in the MCF-7-aromatase cells, compared with that in the MCF
      7-GFP cells. WST-1 assay showed that the cell proliferation rate of MCF-7
      aromatase cells treated with 1 and 10 nmol/L testosterone was 1.43- and 1.53-fold
      higher than that of the control cells, respectively. The proliferation rate of
      MCF-7-aromatase cells treated with 1 and 10 nmol/L E2 was 1.41- and 1.55-fold
      higher than that of the control cells, respectively. In contrast, the
      proliferation rate of MCF-7-GFP cells treated with 10 nmol/L testosterone was
      1.12-fold higher than that of the control cells, and the proliferation rate of
      MCF-7-GFP cells treated with 1 and 10 nmol/L E2 was 1.41- and 1.51-fold higher
      than that of the control cells, respectively. Letrozole treatment significantly
      inhibited the testosterone-induced proliferation ability of MCF-7-aromatase cells
      in a dose-dependent manner and the IC50 value was 5.3 nmol/L. In contrast,
      letrozole treatment showed no inhibitory effect on the proliferative ability of
      MCF-7-LR cells and the IC50 value was >1000 nmol/L. CONCLUSIONS: MCF-7-aromatase
      and MCF-7-LR cells exhibit different response to letrozole treatment, which
      provides an important basis for further investigating the mechanism of letrozole
      resistance.

PMID- 24119902
TI  - [Discrepancy between radiological and pathological sizes of renal masses].
AB  - OBJECTIVE: To investigate the differences between tumor sizes measured by
      preoperative computed tomography (CT) imaging and pathologic examination of
      surgical specimens in Chinese patients who received extirpative surgery for renal
      tumors. METHODS: From September 2008 to September 2010, 204 patients with renal
      tumors treated in the Renji Hospital were enrolled in this study, and their
      clinicopathological data were collected and analyzed. The paired Student's t-test
      was used to compare the mean radiological tumor maximum diameter and the mean
      pathological tumor maximum diameter. All cases in which post-operative down
      staging or up-staging occurred due to the discrepancy between radiological and
      pathological tumor maximum diameters were identified. In addition, the
      relationship between radiological and pathological tumor maximum diameters and
      histological subtypes was analyzed. RESULTS: Overall, the radiological mean
      maximum diameter of tumors on CT was 48.3 mm and the pathological mean maximum
      diameter was 47.0 mm. On average, CT overestimated pathological size by 1.3 mm (P
      = 0.018). CT overestimated pathological tumor size in 111 (54.4%) patients,
      underestimated in 71 (34.8%) patients and equal pathological size in 22 (10.8%)
      patients. Among the 190 patients with pT1 or pT2 tumors, there was a discrepancy
      between clinical and pathological staging in 35 (18.4%) patients. Of these, 29
      (15.3%) patients were down-staged post-operatively and 6 (3.2%) were up-staged.
      When subjects were categorized according to radiographic tumor size associated
      with clinical stage, statistically significant difference (average of 1.76 mm)
      was observed between radiographic and pathologic maximum diameters ranging 41-70
      mm (P = 0.035). For clear cell carcinoma, mean radiographic tumor maximum
      diameter was significantly larger than the pathologic maximum diameter by 1.69 mm
      (P = 0.003). CONCLUSIONS: There is a statistically significant but small
      difference (1.3 mm) between mean radiological and mean pathological tumor maximum
      diameters. For some patients, this difference leads to a discrepancy between
      clinical and pathological staging, which may have implications on pre-operative
      clinical decision and prognosis prediction.

PMID- 24119903
TI  - [Detection of micrometastases and its clinical significance in sentinel and non
      sentinel lymph nodes from early cervical carcinoma].
AB  - OBJECTIVE: To investigate the clinical significance of micrometastasis detection
      in sentinel lymph nodes (SLN) from patients with early cervical carcinoma.
      METHODS: Thirty patients with early cervical carcinoma were studied to identify
      SLN intraoperatively using methylene blue. One lymph node was removed randomly
      from palpable SLN and other pelvic lymph nodes (nSLN) in each patient, so 268
      lymph nodes were collected and cut into two halves, one half of the lymph node
      was used to analyze the expression of cytokeratin 19 (CK19) mRNA by real-time
      fluorescence quantitative polymerase chain reaction to determine the presence of
      micrometastasis, the other half was examined by routine histology with HE
      staining. RESULTS: 67 SLNs were detected in 28 cases (93.3%). Pelvic lymph nodes
      of 6 cases were confirmed pathological metastasis. The sensitivity of SLN
      detection was 66.7%, the accuracy rate was 96.4%, and the false negative rate was
      16.7%. Among 268 lymph nodes (including 9 lymph nodes with pathological
      metastasis) detected by real-time fluorescence quantitative polymerase chain
      reaction, 68 lymph nodes were pathological negative but had micrometastasis,
      accounting for 26.3% (68/259) in pathologically negative lymph nodes. Among 24
      patients with pathological negative lymph nodes, 16 cases had micrometastasis,
      accounting for 66.7% in those patients. Among 16 patients with micrometastasis,
      SLN of 3 cases were negative, but nSLN were micrometastasis, so the SLN false
      negative rate rose to 18.2%. There were no significant relationships between
      pelvic lymph nodes micrometastasis and perivascular space involvement, deep
      stromal invasion and tumor grade (all P > 0.05). The micrometastasis rate of nSLN
      in patients with SLN micrometastasis was 100%, significantly higher than that in
      the patients with SLN non-micrometastasis (27.3%, P < 0.01). CONCLUSIONS: Real
      time fluorescence quantitative polymerase chain reaction is a sensitive method to
      detect SLN micrometastasis. SLN micrometastasis may be an effective complement to
      SLN pathology to predict nSLN metastasis. Pelvic lymph nodes micrometastases have
      no significant relationship with pathological risk factors in cervical cancer and
      prognosis of patients.

PMID- 24119904
TI  - [Expression and clinical significance of vascular endothelial growth factor-C and
      nm23-H1 in stage II and III colorectal carcinomas].
AB  - OBJECTIVE: To discuss the expression and clinical significance of VEGF-C and nm23
      H1 in stage II and III colorectal carcinomas. METHODS: SP immunohistochemical
      staining was employed to determine the expression of vascular endothelial growth
      factor-C (VEGF-C) and nm23-H1 in the tumor tissues of 110 cases of stage II and
      III colorectal carcinomas and in the adjacent mucosal tissues of 53 cases as
      control, and analyze their correlation with cliniopathological features and
      prognosis. RESULTS: The positive expression of VEGF-C in the carcinoma tissues
      was 71.8%, significantly higher than that in the adjacent mucosal tissues (22.6%,
      P < 0.001). The positive expression of nm23-H1 in the carcinoma tissues was
      57.3%, significantly lower than that in the adjacent mucosal tissues (90.6%, P <
      0.001). The expression of VEGF-C was significantly correlated with lymph node
      metastasis (P < 0.05), and the nm23-H1 expression was significantly correlated
      with lymph node metastasis and pathological type (P < 0.05). The expression of
      VEGF-C and nm23-H1 did not show a significant correlation with age, gender,
      primary tumor site, tumor size and depth of invasion (P > 0.05). The VEGF-C
      expression was negatively related with nm23-H1 expression in colorectal carcinoma
      (r = -0.361, P < 0.001). The median overall survival (MOS) and median disease
      free survival (MDFS) of 110 patients with colorectal carcinoma were 55 and 48
      months, respectively. The colorectal patients with different VEGF-C and nm23-H1
      expression showed significant differences in the 5-year OS rate and 5-year DFS
      rate (P < 0.001). The patients with negative VEGF-C expression and positive nm23
      H1 expression had a better prognosis. CONCLUSIONS: The joint detection of VEGF-C
      and nm23-H1 expression is very promising in prediction of the prognosis of
      patients with stage II and III colorectal carcinoma. However, whether it can be
      used as a marker in prognosis judgment needs further investigation.

PMID- 24119905
TI  - [Expression of serum human epididymis protein 4 in epithelial ovarian cancer and
      its correlation with prognosis].
AB  - OBJECTIVE: To study the characteristics of HE4 expression in patients with
      epithelial ovarian cancer, and to evaluate whether the pre-treatment serum human
      epididymis protein 4 (HE4) level is an independent prognostic factor in the
      patients. METHODS: The clinicopathological characteristics and follow-up
      information of 112 patients with epithelial ovarian cancer were collected. The
      pre-treatment serum samples from these patients were measured for HE4 and CA125
      expression. Serum HE4 levels were tested by a quantitative enzyme-linked
      immunosorbent assay (ELISA) and serum CA125 levels were tested using Elecsys kit.
      The correlation of HE4 and CA125 expressions with overall survival and other
      clinical data were analyzed. RESULTS: The median level of pre-treatment serum HE4
      and CA125 in the 112 patients was 415.5 pmol/L (26.9-3253.5 pmol/L) and 699 U/ml
      (5-17 694 U/ml), respectively. Serum HE4 level before treatment was significantly
      related to grade (r = 0.21, P = 0.037), stage (r = 0.40, P = 0.001), amount of
      ascites (r = 0.39, P = 0.001), serum CA125 level (r = 0.53, P = 0.001) and
      residual disease after surgery (r = 0.22, P = 0.027), but was not related to
      menopausal stauts (P = 0.115), revealed by Spearman correlation test.However,
      logistic multivariate regression analysis indicated that residual tumor size was
      not significantly correlated with pre-operative HE4 level (P = 0.259). The mean
      survival of the 112 patients was 53 months. Log rank test indicated that the
      overall survival in patients with higher HE4 level was significantly shorter than
      those with lower HE4 level (P = 0.001). Multivariate Cox proportional hazard
      model analysis revealed that the pre-treatment serum HE4 level and residual tumor
      size were independent prognostic factors for overall survival (P = 0.044 and P =
      0.048). CONCLUSION: Pre-treatment serum HE4 level is a valuable prognostic factor
      for the overall survival in patients with epithelial ovarian cancer.

PMID- 24119906
TI  - [Expression and prognostic value of regulatory T cells and M2 macrophages in
      diffuse large B-cell lymphoma tissues].
AB  - OBJECTIVE: To explore the prognostic value of regulatory T cells (Tregs) and M2
      macrophages in diffuse large B-cell lymphoma (DLBCL) tissues. METHODS: The
      expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of
      DLBCL, and it was statistically analyzed whether their expressions correlate with
      clinical data and prognosis in patients with DLBCL. RESULTS: The density of M2
      macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher
      than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2
      macrophages was significantly positively correlated with regulatory T cells
      expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship
      with extranodal involvement (P < 0.05). Cox regression analysis showed that the
      expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P <
      0.05). CONCLUSIONS: Combined detection of the expression of CD163 and Foxp3
      proteins and then evaluation of the amount of M2 macrophages and Tregs can be
      used to more closely predict the prognosis for DLBCL patients.

PMID- 24119907
TI  - [Long-term outcomes of endoscopic argon plasma coagulation (APC) therapy for
      early esophageal cancer and precancerous lesions].
AB  - OBJECTIVE: To evaluate the long-term outcomes of endoscopic argon plasma
      coagulation (APC) therapy for early esophageal cancer and precancerous lesions.
      METHODS: One-hundred and seventy-one cases with early esophageal cancer
      (intramucosal carcinoma) and precancerous lesions were treated by APC from 1994
      to 2005, and all the cases were followed up. One-hundred and sixty-eight (98.2%)
      cases were follow-up by endoscopic examination for several times. On average,
      each patient was endoscopically examined 2.8 times. The follow-up rate was 100%.
      RESULTS: The precancerous lesion group had 160 patients. They were followed up
      for 5 years. 11 patients died of causes unrelated to cancer. The lesions
      developed into esophageal squamous cell carcinoma in five patients ( 2 died and 3
      underwent esophagectomy). The remaining 144 cases survived without cancer. In
      this group, the esophageal cancer incidence rate is only 3.1% (5/160). The early
      cancer (i.e. intramucosal cancer) group had 11 patients. During the 5-year follow
      up period, two patients died of causes unrelated to cancer,six patients had
      recurrence (4 patients died and 2 patients underwent esophagectomy), and only 3
      patients survived without cancer. Therefore, the 5-year survival rate was only
      27.3% (3/11). CONCLUSIONS: The APC therapy for precancerous lesions of the
      esophagus is effective and successful. Indications should be carefully considered
      when treating early esophageal cancer such as intramucosal carcinoma by APC
      therapy.

PMID- 24119908
TI  - [Application value of sentinel node biopsy in early stage oral tongue cancer with
      clinically negative neck].
AB  - OBJECTIVE: To evaluate the liability of sentinel node biopsy in the treatment of
      early stage oral tongue carcinoma with clinically negative neck. METHODS:
      Eighteen patients with T1 or T2 oral tongue carcinoma were enrolled in the
      prospective study. Preoperative lymphoscintigraphy and intra-operative hand-held
      gamma probe techniques were used to detect the sentinel lymph nodes. The sentinel
      lymph node biopsies were sent to frozen section pathology and the results were
      compared with specimen of routine selective neck dissection (I ~ III or I ~ IV).
      The accuracy of cervical metastasis prediction was compared between sentinel node
      biopsy and tumor thickness. RESULTS: Sentinel lymph nodes were identified in all
      18 cases. The numbers of sentinel lymph nodes of level Ib, IIa and III were 6, 22
      and 2, respectively. In this series, positive sentinel lymph nodes were revealed
      in 4 cases, which were also positive in the postoperative routine histology.In
      other cases, both sentinel lymph nodes and routine histology were negative. Both
      the sensitivity and specificity were 100%. Sentinel lymph node biopsy obviously
      improved the specificity of predicting cervical metastasis comparing with the
      tumor thickness. (100% vs. 36.4%). CONCLUSION: Sentinel node biopsy is effective
      and reliable in the treatment of early stage oral tongue cancer, and deserves
      clinical application.

PMID- 24119909
TI  - [Clinicopathological features and prognosis of triple-negative breast cancer].
AB  - OBJECTIVE: This study was conducted to analyze the clinicopathological
      characteristics and patient survival factors in triple-negative breast cancer
      (TNBC). METHODS: A retrospective analysis was performed on 14 506 breast cancer
      patients admitted to the Departmrnt of Breast Surgery, Tianjin Medical University
      Cancer Hospital from January 2004 to June 2010. The correlation of pathological
      characteristics, recurrence time and patterns, and prognosis with TNBC was
      analyzed. RESULTS: Among the 14 506 cases, there were 1886 (13.0%) cases of
      triple-negative breast cancer, 7282 (50.2%) cases of luminal A breast caner, 3380
      (23.3%) cases of luminal B breast caner, and 1958 (13.5%) cases of HER-2
      overexpressing breast cancer. Compared with the other groups, the triple-negative
      breast cancer patients had significantly higher histological grade, lower
      percentage of invasive breast ductal carcinoma and higher pathological stage (P <
      0.001) . The 5-year disease-free survival rate of the triple negative breast
      cancer was 79.5%, significantly lower than that of the other subtype breast
      cancer (P < 0.001), but the difference in 5-year overall survival rate was not
      significant (P = 0.113). The independent factors of DFS in TNBC including: age,
      tumor size, clinical stage, surgery and chemotherapy (P < 0.05). CONCLUSION:
      Compared with the other subtype breast cancers, the patients with triple-negative
      breast cancer have higher histological grade, lower percentage of invasive breast
      ductal carcinoma and higher pathological stage, and they also have a poor
      prognosis.

PMID- 24119910
TI  - [Efficacy and safety of low-frequency rotary magnetic fields in the treatment of
      patients with advanced malignant tumors].
AB  - OBJECTIVE: To investigate the clinical efficacy and safety of low-frequency
      rotary magnetic fields in the treatment of patients with advanced malignant
      tumors. METHODS: 137 patients with advanced malignant tumors were exposed to 400
      r/min, 0.4 T low-frequency rotary magnetic fields. An area including the primary
      tumor, local metastasis and metastatic lymph nodes was exposed daily, 2 hours per
      day for 30~50 days (average time of 42 days). RESULTS: All of the 137 patients
      completed the low-frequency rotary magnetic field treatment. There were 28 cases
      with complete response, 54 cases with partial response, and the clinical benefit
      rate was 59.9%. The tumor type, initial KPS and QOL showed statistical
      significance in the clinical benefit rate (P < 0.05). The median overall survival
      was 12 months, and the 1-year, 2-year and 3-year survival rates were 47.0%,
      11.8%, 3.4%, respectively. The tumor type, initial KPS and QOL were identified by
      univariate log-rank test as significant prognostic factors for overall survival
      (P < 0.05). Multivariate analysis showed that the initial QOL was an independent
      prognostic factors (P = 0.037) . During the treatment, asthenia and local pain
      were observed in 11 patients, and 6 patients had mild tachycardia (increased 3 to
      5/min) and/or temperature elevation (0.5 to 1.0 degrees C). All above symptoms
      disappeared spontaneously. No treatment-related death was observed. CONCLUSIONS:
      Low-frequency rotary magnetic fields is an effective and safe method in the
      treatment of patients with advanced malignant tumors, and may prolong survival
      significantly.

PMID- 24119911
TI  - [Relationship between single nucleotide polymorphisms and its haplotype of X-ray
      repair cross complementing group 1 and susceptibility of pancreatic carcinoma].
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of XRCCl gene
      polymorphisms and its haplotype on the susceptibility of pancreatic carcinoma.
      METHODS: Peripheral blood DNA was extracted from 210 pancreatic carcinoma
      patients and 213 control subjects. SNaPshot technique was used for genotyping
      seven SNP sites of the XRCCl gene (rs3213403, rs25487, rs1799782, rs731420,
      rs1001581, rs12611088, and rs3213282). Logistic regression model was performed to
      analyze the relationship of different genotypes or haplotype and the
      susceptibility of pancreatic carcinoma. RESULTS: The frequency for allele A at
      site rs25487 in the case group was significantly higher than that in the control
      group (P < 0.05). The frequency of GG, GA and AA genotype between the case group
      and control group had statistically significant differences (P < 0.05). Compared
      with GG genotype, the risk of pancreatic carcinoma in the subjects carrying
      mutated allele A (GA+AA) was increased by 0.648 times (P < 0.05). Among them the
      pancreatic carcinoma risk of individuals carrying A allele was increased by 0.552
      times compared with the individuals carrying G allele. The frequency of allele
      and genotype at site rs1799782 in the case group and control group had a
      significant difference (P < 0.05). Compared with the CC genotype, the risk of
      pancreatic carcinoma in the subjects carrying mutated allele T (CT+TT) was
      increased by 0.683 times. Among them the pancreatic carcinoma risk of individuals
      carrying T allele was increased by 0.549 times compared with the individuals
      carrying C allele. Significant differences were observed in linkage
      disequilibrium between any two of the seven SNPs (P < 0.05), the frequency of H4
      AGCCCGC, H6-GGCCCGG or H7-AGCCTAG haplotypes was significantly lower in the case
      group than that in the control group (P < 0.05). CONCLUSIONS: The single
      nucleotide polymorphisms of rs25487 and rs1799782 for XRCC1 gene may be
      correlated with the occurrence of pancreatic carcinoma. The haplotypes of H4
      AGCCCGC, H6-GGCCCGG and H7-AGCCTAG might be a potential genetic protective factor
      for the occurrence of pancreatic carcinoma.

PMID- 24119912
TI  - [The Diagnosis and Treatment Guideline of Chinese Patients with EGFR Mutation and
      ALK Fusion Gene-Positive Non-Small Cell Lung Cancer (2013 Version)].

PMID- 24119913
TI  - Pathogen recognition receptor crosstalk in respiratory syncytial virus sensing: a
      host and cell type perspective.
AB  - Human respiratory syncytial virus (RSV) is a major cause of acute lower
      respiratory tract infection in young children, immunocompromised adults, and the
      elderly. The innate immune response plays a pivotal role in host defense against
      RSV, but whether severe outcomes following RSV infection result from excessive or
      poor innate immune recognition remains unclear. Recent research suggests a
      situation in which crosstalk between families of pattern recognition receptors
      (PRRs) occurs in a cell type-dependent manner. The current challenge to empower
      novel therapeutic approaches and vaccine development is to confirm the role of
      the individual receptors in RSV pathogenesis in humans. 

PMID- 24119914
TI  - Astrocyte elevated gene-1 overexpression in histologically favorable Wilms tumor
      is related to poor prognosis.
AB  - OBJECTIVE: Astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and
      progression in various types of human cancers. However, the status of AEG-1
      expression and its significance in Wilms tumor are still unclear. In this study,
      we investigated the expression of AEG-1 and evaluated its clinical and prognostic
      significance in favorable-histology Wilms tumor (FHWT). MATERIALS AND METHODS:
      Immunohistochemistry was performed to examine AEG-1 protein expression in
      paraffin-embedded tissues from 38 FHWT patients. All patients underwent radical
      nephrectomy from January 2003 to June 2008 with subsequent therapy according to
      National Wilms Tumor Study Group protocols. Statistical analyses were performed
      to evaluate the association between AEG-1 expression and clinical parameters.
      RESULTS: We found high AEG-1 expression in 17 of 38 (44.7%) patients. AEG-1
      expression was significantly correlated with clinical stage (p = 0.019) and
      status of recurrence (p = 0.023). Importantly, patients with high AEG-1
      expression had a shorter disease-free survival and overall survival compared with
      those with low AEG-1 expression (p = 0.011 and p = 0.013). CONCLUSION: AEG-1
      expression is associated with FHWT outcome in this study, and AEG-1 may represent
      a novel and valuable predictor for prognostic evaluation of FHWT patients.

PMID- 24119915
TI  - Health-related quality of life scores after intensive care are almost equal to
      those of the normal population: a multicenter observational study.
AB  - INTRODUCTION: Health-related quality of life (HRQoL) in patients treated in
      intensive care has been reported to be lower compared with age- and sex-adjusted
      control groups. Our aim was to test whether stratifying for coexisting conditions
      would reduce observed differences in HRQoL between patients treated in the ICU
      and a control group from the normal population. We also wanted to characterize
      the ICU patients with the lowest HRQoL within these strata. METHODS: We did a
      cross-sectional comparison of scores of the short-form health survey (SF-36)
      questionnaire in a multicenter study of patients treated in the ICU (n = 780) and
      those from a local public health survey (n = 6,093). Analyses were in both groups
      adjusted for age and sex, and data stratified for coexisting conditions. Within
      each stratum, patients with low scores (below -2 SD of the control group) were
      identified and characterized. RESULTS: After adjustment, there were minor and
      insignificant differences in mean SF-36 scores between patients and controls.
      Eight (n = 18) and 22% (n = 51) of the patients had low scores (-2 SD of the
      control group) in the physical and mental dimensions of SF-36, respectively.
      Patients with low scores were usually male, single, on sick leave before
      admission to critical care, and survived a shorter time after being in ICU.
      CONCLUSIONS: After adjusting for age, sex, and coexisting conditions, mean HRQoL
      scores were almost equal in patients and controls. Up to 22% (n = 51) of the
      patients had, however, a poor quality of life as compared with the controls (-2
      SD). This group, which more often consisted of single men, individuals who were
      on sick leave before admission to the ICU, had an increased mortality after ICU.
      This group should be a target for future support.

PMID- 24119917
TI  - Fracture risk of lithium-disilicate ceramic inlays: a finite element analysis.
AB  - OBJECTIVES: In the present study, lithium-disilicate ceramic inlays should be
      analyzed biomechanically according to their thickness and dimension, and it
      should be clarified as to whether there is a significant relationship between the
      inlay volume and the induced tensile stress level. METHODS: Using a new
      parametric CAD modeling procedure, 27 lithium-disilicate ceramic inlays with
      various parameters of "depth", "width", "angle" and restoration volume were
      generated. These inlays were integrated into the CAD model of a lower molar
      created from the CT data of an anatomical preparation. The resulting CAD models
      were, finally, three-dimensionally cross-linked to FEM models. After applying a
      compressive force of 200 N, Principal Tensile Stresses (PTSs) could be measured
      in the inlay. The values were subject to statistical analysis afterwards.
      RESULTS: The volume of the inlay restorations varied between 35.7 mm(3) and
      82.5mm(3). The maximum PTS values (n=10) only showed a slight negative
      correlation with the inlay volume. The correlation coefficient according to
      Spearman was -0.082 (p <= 0.001). If the highest 1000 PTS values of each inlay
      were considered (n=1000), the correlation coefficient was further reduced to
      +0.068 (p <= 0.001). No significant correlation between the inlay volume and the
      induced PTS level could be detected. SIGNIFICANCE: Under the conditions and
      limitations of the present FEM study, the inlay volume did not significantly
      influence the tensile stress level of ceramic inlays. The results may support the
      thesis that volume-reduced all-ceramic inlays might not have an increased
      fracture risk. Further studies are needed to confirm this.

PMID- 24119916
TI  - The effect of insecticide-treated bed nets on the incidence and prevalence of
      malaria in children in an area of unstable seasonal transmission in western
      Myanmar.
AB  - BACKGROUND: Insecticide-treated bed nets (ITN) reduce malaria morbidity and
      mortality consistently in Africa, but their benefits have been less consistent in
      Asia. This study's objective was to evaluate the malaria protective efficacy of
      village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness
      of ITN compared with extending early diagnosis and treatment services. METHODS: A
      cluster-randomized controlled trial was conducted in Rakhine State to assess the
      efficacy of ITNs in preventing malaria and anaemia in children and their
      secondary effects on nutrition and development. The data were aggregated for each
      village to obtain cluster-level infection rates. In total 8,175 children under 10
      years of age were followed up for 10 months, which included the main malaria
      transmission period. The incidence and prevalence of Plasmodium falciparum and
      Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in
      the area were studied concurrently. The trial data along with costs for current
      recommended treatment practices were modelled to estimate the cost-effectiveness
      of ITNs compared with, or in addition to extending the coverage of early
      diagnosis and treatment services. RESULTS: In aggregate, malaria infections,
      spleen rates, haemoglobin concentrations, and weight for height, did not differ
      significantly during the study period between villages with and without ITNs,
      with a weighted mean difference of -2.6 P. falciparum episodes per 1,000 weeks at
      risk (95% Confidence Interval -7 to 1.8). In areas with a higher incidence of
      malaria there was some evidence ITN protective efficacy. The economic analysis
      indicated that, despite the uncertainty and variability in their protective
      efficacy in the different study sites, ITN could still be cost-effective, but not
      if they displaced funding for early diagnosis and effective treatment which is
      substantially more cost-effective. CONCLUSION: In Western Myanmar deployment of
      ITNs did not provide consistent protection against malaria in children living in
      malaria endemic villages. Early diagnosis and effective treatment is a more cost
      effective malaria control strategy than deployment of ITNs in this area where the
      main vector bites early in the evening, often before people are protected by an
      ITN.

PMID- 24119918
TI  - Mechanism of detoxification of the cationic antibacterial monomer 12
      methacryloyloxydodecylpyridiniumbromide (MDPB) by N-acetyl cysteine.
AB  - OBJECTIVES: The protective effects of N-acetyl cysteine (NAC) against
      cytotoxicity induced by conventional dental resin monomers have been widely
      documented. However, its effectiveness to detoxify cationic antibacterial
      monomers has not yet been elucidated. The aim of the present study was to
      investigate the possible protective effects of NAC against the cytotoxicity of 12
      methacryloyloxydodecylpyridiniumbromide (MDPB) and explore the role of adduct
      formation in NAC-directed detoxification. METHODS: The influences of NAC on the
      cytotoxicity of MDPB were studied in mouse osteoblast-like MC3T3-E1 cells using
      the MTT assay. Ultra-performance liquid chromatography (UPLC) and liquid
      chromatography-mass spectrometry (LC-MS) analysis were performed to investigate
      the possible chemical reaction between NAC and MDPB. RESULTS: While only slight
      reduction in the cytotoxicity of MDPB by NAC was observed immediately after
      mixing with MDPB, remarkable protection against MDPB-induced cell death was
      detected when the mixture was tested after 24h of pre-incubation. UPLC and LC-MS
      analysis revealed that chemical binding of MDPB and NAC occurred under neutral
      conditions after 24h of pre-incubation. SIGNIFICANCE: Our findings suggest that
      NAC reduces the toxicity of the cationic antibacterial monomer MDPB, and adduct
      formation is partially responsible for the detoxification ability of NAC against
      MDPB-induced cell damage.

PMID- 24119919
TI  - Improved polymerization efficiency of methacrylate-based cements containing an
      iodonium salt.
AB  - OBJECTIVE: This study evaluated the effect of adding diphenyliodonium
      hexafluorphosphate (DPI) as a third component of the free-radical photoinitiator
      system of model resin cements on their photopolymerization kinetics/stress and
      fundamental properties. METHODS: A model resin cement containing a 1:1 mass ratio
      of 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane and
      triethyleneglycol dimethacrylate was obtained. Camphorquinone (1 mol%) and 2
      (dimethylamino)ethyl methacrylate (2 mol%) were added to monomer blend. Six
      mixtures were obtained by incorporation of 0 (control), 0.25, 0.5, 1, 2, or 4
      mol% of DPI. The cements were loaded with a 60% mass fraction of silanated glass
      fillers. Polymerization kinetics (using Fourier-transform near-infrared
      spectroscopy), flexural strength and modulus, water uptake/solubility, and
      polymerization stress were assessed. Data were statistically analyzed using one
      way ANOVA and Student-Newman-Keuls' test (P <= 0.05). RESULTS: In the DPI
      modified materials, the onset of autodeceleration occurred earlier and at higher
      conversion compared with the control cement. The addition of DPI also led to a
      more active early-stage polymerization. The flexural modulus was generally higher
      for DPI-containing materials. Water uptake and solubility were generally lower
      for materials with DPI fractions >= 0.5%. Significant increase of polymerization
      stress was observed only in the group with 1 mol% of DPI compared with the
      control cement. SIGNIFICANCE: The effect of DPI on the photopolymerization
      reactivity of the cement is concentration-dependent; the use of DPI could result
      in better polymerization efficiency of resin-based cements.

PMID- 24119920
TI  - The role of somatic health problems in the recognition of depressive and anxiety
      disorders by general practitioners.
AB  - BACKGROUND: Recognition of depression and anxiety by general practitioners (GPs)
      is suboptimal and there is uncertainty as to whether particular somatic health
      problems hinder or facilitate GP recognition. The objective of this study was to
      investigate the associations between somatic health problems and GP recognition
      of depression and anxiety. METHODS: We studied primary care patients with a DSM
      IV based psychiatric diagnosis of depressive or anxiety disorder during a face-to
      face interview (n=778). GPs' registrations of depression and anxiety diagnoses,
      based on medical file extractions, were compared with the DSM-IV based
      psychiatric diagnoses as reference standard. Somatic health problems were based
      on self-report of several chronic somatic diseases and pain symptoms, using the
      Chronic Pain Grade (CPG), during the interview. RESULTS: Depression and anxiety
      was recognized in sixty percent of the patients. None of the health problems were
      negatively associated with recognition. Greater severity of pain symptoms
      (OR=1.18, p=.02), and chest pain (OR=1.56, p=.02), in particular, were associated
      with more GP recognition of depression and anxiety. Mediation analyses showed
      that depression and anxiety in these patients were better recognized through the
      presence of more severe psychiatric symptoms. LIMITATIONS: Some specific chronic
      diseases had low prevalence. CONCLUSIONS: This study shows that the presence of
      particular chronic diseases does not influence GP recognition of depression and
      anxiety. GPs tend to recognize depression and anxiety better in patients with
      pain symptoms, partly due to more severe psychiatric symptoms among those with
      pain.

PMID- 24119921
TI  - Common mental disorders in women and men in the first six months after the birth
      of their first infant: a community study in Victoria, Australia.
AB  - INTRODUCTION: Studies of postpartum mental health have focused predominantly on
      women and on depression. There is limited evidence regarding men's postpartum
      mental health and about other common mental disorders, such as anxiety and
      adjustment disorders, which may also be relevant at this life phase. The main aim
      of this study was to establish the period prevalence of depression, anxiety, and
      adjustment disorders in primiparous women and their male partners in the first
      six months postpartum METHODS: English-speaking couples were recruited in five
      local government areas in Victoria, Australia. Women and men completed separate
      telephone interviews which included the Edinburgh Postnatal Depression Scale
      (EPDS) and selected Depression and Anxiety modules of the Composite International
      Diagnostic Interview. DSM-IV criteria were used to classify adjustment disorders,
      based on subclinical symptoms not meeting criteria for diagnoses of major or
      minor depression or generalised anxiety disorder. The main outcome was any common
      mental disorder (depression, anxiety or adjustment disorder) in the first six
      months postpartum RESULTS: Complete data were available for 172 couples. The 6
      month period prevalence of mental health problems was 33% for women and 17% for
      men. The most common diagnosis in both women and men was adjustment disorder with
      anxiety symptoms LIMITATIONS: Unpartnered women and men, women whose partners
      were not willing to participate and those who did not have sufficient English
      fluency to complete the interviews were excluded from the sample. The results of
      this study cannot be generalised to these populations. CONCLUSION: The most
      common postnatal mental health problem in both women and men in this community
      sample was anxiety.

PMID- 24119922
TI  - Lung cancer in Northern Portugal: A hospital-based study.
AB  - INTRODUCTION: Lung cancer is the deadliest cancer worldwide. In Portugal, the
      disease remains the main cause of cancer death in males. AIM: This study aims to
      evaluate the demographic and clinical characteristics of lung cancer patients
      diagnosed and treated in northern Portugal hospitals from 2000 to 2010. PATIENTS
      AND METHODS: Twelve hospitals in the north of Portugal contributed to this study.
      The demographic and clinic characteristics of the patients registered in each
      hospital from 2000 to 2010 and the patterns of their occurrence were analyzed.
      RESULTS: During an 11-year period (2000-2010), 9767 lung cancer patients were
      registered in the participating hospitals. Comparing the number of the patients
      registered in the year 2000 to those registered during 2010, there was a
      significant increase in lung cancer cases. Females represent only 20% of the
      total registered lung cancer cases; however, during the study period, the number
      of female patients increased by 30%. A significant number of the patients, 3117
      (48.6%), had poor performance status at presentation. The adenocarcinoma
      histology became more preponderant over the study period. Most of the patients
      were diagnosed as stages IIIB or IV: 7206 of 9267 (77.8%). Chemotherapy was the
      treatment of choice for 3529 (40.4%) patients, whereas surgical treatment was
      achieved in 1301 (14.9%) cases. CONCLUSION: A significant number of lung cancer
      patients have been diagnosed and treated in hospitals in northern Portugal, and
      the incidence of the disease among females has been increasing. The overwhelming
      majority of the tumors were diagnosed in advanced stage; nevertheless, surgical
      treatment was possible in 14.9% of the patients.

PMID- 24119923
TI  - Topical application of mitomycin-C as an adjuvant treatment to bronchoscopic
      procedures in post-intubation tracheal stenosis.
AB  - INTRODUCTION: Post-intubation tracheal stenosis (PITS) continues to be
      challenging in terms of diagnosis, management and prevention. Recurrence is
      common because of excessive granulation tissue formation and an insidious process
      of scar contracture. Topical application of mitomycin-C (MMC) as an adjuvant
      treatment for endoscopic management of stenosis has shown good results. The
      authors aimed to evaluate the results of MMC topical application following
      bronchoscopic dilatation as an adjuvant in PITS treatment. METHODS:
      Retrospectively selected patients with PITS who had had rigid bronchoscopy (RB)
      dilatation followed by MMC application as adjuvant to endoscopic treatment. MMC
      in a concentration of 0.4 mg/ml was applied with a cotton stiletto around the
      stenotic lesion and granulation tissue for 3 minutes. RESULTS: Eleven patients
      with PITS, with a median initial tracheal stenosis of 75% of the lumen, underwent
      RB/MMC treatment. Mean MMC sessions performed/patient was 3.5, with good response
      and prolonged decrease in granulation tissue formation in 55% of cases, moderate
      in 18% and relapse in 27%. Mean stenosis improvement was 34%. CONCLUSIONS:
      Topical MMC application at 0.4 mg/ml concentration seems to be associated with
      good results as adjuvant in PITS management with decrease in granulation tissue
      and sustained improvement in lumen diameter.

PMID- 24119924
TI  - A novel technique to quantify the instantaneous mitral regurgitant rate.
AB  - BACKGROUND: The systolic variation of mitral regurgitation (MR) is a pitfall in
      its quantification. Current recommendations advocate using quantitative
      echocardiographic techniques that account for this systolic variation. While
      prior studies have qualitatively described patterns of systolic variation no
      study has quantified this variation. METHODS: This study includes 41 patients who
      underwent cardiovascular magnetic resonance (CMR) evaluation for the assessment
      of MR. Systole was divided into 3 equal parts: early, mid, and late. The MR jets
      were categorized as holosystolic, early, or late based on the portions of systole
      the jet was visible. The aortic flow and left ventricular stroke volume (LVSV)
      acquired by CMR were plotted against time. The instantaneous regurgitant rate was
      calculated for each third of systole as the difference between the LVSV and the
      aortic flow. RESULTS: The regurgitant rate varied widely with a 1.9-fold, 3.4
      fold, and 1.6-fold difference between the lowest and highest rate in patients
      with early, late, and holosystolic jets respectively. There was overlap of peak
      regurgitant rates among patients with mild, moderate and severe MR. The greatest
      variation of regurgitant rate was seen among patients with mild MR. CONCLUSION:
      CMR can quantify the systolic temporal variation of MR. There is significant
      variation of the mitral regurgitant rate even among patients with holosystolic MR
      jets. These findings highlight the need to use quantitative measures of MR
      severity that take into consideration the temporal variation of MR.

PMID- 24119925
TI  - Ectopic acromegaly due to a GH-secreting pituitary adenoma in the sphenoid sinus:
      a case report and review of the literature.
AB  - BACKGROUND: In more than 98% of cases, acromegaly is due to a GH-secreting
      pituitary adenoma. The term "ectopic acromegaly" includes neuroendocrine tumors
      secreting GH releasing hormone (GHRH), usually located in the lungs, thymus and
      endocrine pancreas. Considerably less frequent are cases of ectopic acromegaly
      due to GH-secreting tumors located out of the pituitary fossa; except for one
      isolated case of a well-documented GH-secreting lymphoma, the majority of these
      lesions are located in the sphenoid sinus. CASE PRESENTATION: We present the case
      of a 45 year old woman with acromegaly whose MRI showed an empty sella without
      evidence of a pituitary adenoma but revealed a large mass within the sphenoid
      sinus. She underwent transsphenoidal surgery and the excised sphenoid sinus mass,
      proved to be a GH-secreting adenoma; the sellar floor was intact and no other
      lesions were found in the pituitary fossa. She required postoperative treatment
      with somatostatin analogs and cabergoline for clinical and biochemical control.
      CONCLUSIONS: This case highlights the importance of carefully evaluating the
      structures surrounding the sellar area when a pituitary adenoma is not found with
      currently available imaging techniques. The finding of an intact sellar floor and
      duramater lead us to conclude that the patient's tumor originated de novo from
      embryological pituitary remnants. Upon a careful review of the literature and a
      critical evaluation of our case we found neither clinical nor biochemical
      features that would distinguish an ectopic from the more common eutopically
      located somatotrophinoma.

PMID- 24119926
TI  - Effect of gamma sterilization on microhardness of the cortical bone tissue of
      bovine femur in presence of N-Acetyl-L-Cysteine free radical scavenger.
AB  - Gamma sterilization is usually used to minimize the risk of infection
      transmission through bone allografts. However, it is believed that gamma
      irradiation affects the mechanical properties of allografts and free radical
      scavengers can be used to alleviate the radiation-induced degradation of these
      properties. The aim of this study was to investigate the radioprotective effects
      of N-Acetyl-L-Cysteine (NAC) free radical scavenger on the material properties of
      sterilized bovine cortical bone at microstructure level. Forty-two cortical
      tissue specimens were excised from three bovine femurs and irradiated to 35 and
      70 kGy gamma rays in the presence of 5, 50, and 100 mM concentrations of NAC. The
      localized variations in microhardness were evaluated via indentation in the
      radial and longitudinal directions to examine different regions of the
      microstructures of the specimens, including the osteonal and interstitial
      tissues. A significant increase was observed in the hardness of osteonal,
      interstitial, and longitudinal combined microstructures exposed to 35 and 70 kGy
      radiations (P < 0.05), whereas a relative reduction of the hardness was observed
      in the radial direction. Furthermore, it was found that the application of 50 and
      100 mM NAC during gamma irradiation significantly subsided the hardening in
      longitudinal combined microstructure. Moreover, the reduction of hardness in
      radial direction was suppressed in the presence of 100 mM of NAC. In conclusion,
      the results indicated that NAC free radical scavenger can protect the cortical
      bone against deteriorative effects of ionizing radiation and can be used to
      improve the material properties of sterilized allografts.

PMID- 24119927
TI  - Recent lessons for the management of bone and joint infections.
AB  - The epidemiology and clinical manifestations of osteoarticular infections are
      changing primarily as a result of the emergence of community-acquired methicillin
      resistant Staphylococcus aureus infections. Multifocal disease, venous thrombosis
      and pathologic fractures are manifestations of CA-MRSA osteomyelitis. MRI is the
      diagnostic imaging modality of choice for musculoskeletal infections.
      Nafcillin/oxacillin or cefazolin remains the antibiotic of choice for treating
      infections caused by MSSA. A beta-lactam antibiotic is recommended for Kingella
      kingae. Vancomycin and clindamycin are the first line agents for treating
      osteomyelitis caused by CA-MRSA. A short course of parenteral antibiotics
      followed by appropriate oral antibiotics is equivalent to total course of
      parenteral antibiotics for most patients and avoids the risks associated with
      PICCs. Surgical drainage of subperiosteal abscesses and surrounding pyomyositis
      is common with S. aureus clones currently circulating. Collaboration with
      hematologists for managing patients with venous thromboses is recommended. 

PMID- 24119928
TI  - It is not only the cat that did it: how to prevent and treat congenital
      toxoplasmosis.
AB  - The apicomplexan parasite Toxoplasma gondii was discovered a little over one
      hundred years ago and was soon recognized as a pathogen responsible for
      congenital infection. But detailed understanding of its epidemiology emerged only
      after 1970 with the discovery of its life cycle. In the last ten years, high
      resolution molecular tools have allowed the characterization of various strain
      types with different virulence patterns, and current studies are exploring the
      distribution of these different genotypes. In parallel, sophisticated diagnostic
      tools have been developed and awareness of disease burden has led some European
      countries with high prevalence rates to implement screening of pregnant women. In
      this article, the screening options and therapies used to prevent congenital
      toxoplasmosis are dissected in the light of recent data from cohort studies and
      other epidemiological data. 

PMID- 24119929
TI  - Childhood TB: when to think of it and what to do when you do.
AB  - Although childhood tuberculosis has declined dramatically in the UK over the last
      century, it is now increasing again and globally childhood tuberculosis still
      accounts for a significant proportion of the tuberculosis disease burden.
      Children may present with non-specific symptoms, and because of the
      paucibacillary nature of disease and the difficulty of producing sputum samples,
      tuberculosis in children is often difficult to diagnose. Apart from the
      traditional diagnostic methods, like chest X-ray, tuberculin skin testing and
      mycobacterial staining or culture, new diagnostic strategies have been developed.
      In particular, immune-based diagnostics, such as interferon-gamma release assays,
      have now been introduced for clinical use. However these tests do not offer
      substantial improvements in sensitivity over tuberculin skin testing for the
      diagnosis of active disease. Further research is needed to develop better
      diagnostic tests for tuberculosis in children. 

PMID- 24119930
TI  - Heteroaggregation and sedimentation rates for nanomaterials in natural waters.
AB  - Exposure modeling of engineered nanomaterials requires input parameters such as
      sedimentation rates and heteroaggregation rates. Here, we estimate these rates
      using quiescent settling experiments under environmentally relevant conditions.
      We investigated 4 different nanomaterials (C60, CeO2, SiO2-Ag and PVP-Ag) in 6
      different water types ranging from a small stream to seawater. In the presence of
      natural colloids, sedimentation rates ranged from 0.0001 m d(-1) for SiO2-Ag to
      0.14 m d(-1) for C60. The apparent rates of heteroaggregation between
      nanomaterials and natural colloids were estimated using a novel method that
      separates heteroaggregation from homoaggregation using a simplified Smoluchowski
      based aggregation-settling equation applied to data from unfiltered and filtered
      waters. The heteroaggregation rates ranged between 0.007 and 0.6 L mg(-1) day(
      1), with the highest values observed in seawater. We argue that such system
      specific parameters are key to the development of dedicated water quality models
      for ENMs.

PMID- 24119931
TI  - An integrated catalyst of Pd supported on magnetic Fe3O4 nanoparticles:
      simultaneous production of H2O2 and Fe2+ for efficient electro-Fenton degradation
      of organic contaminants.
AB  - A novel electro-Fenton process based on Pd-catalytic production of H2O2 from H2
      and O2 has been proposed recently for transforming organic contaminants in
      wastewaters and groundwater. However, addition of Fe(II) complicates the
      operation, and it is difficult to recycle Pd catalyst after treatment. This study
      attempts to synthesize an integrated catalyst by loading Pd onto magnetic Fe3O4
      nanoparticles (Pd/MNPs) so that H2O2 and Fe(2+) can be produced simultaneously in
      the electrolytic system. In an undivided electrolytic cell, phenol, a probe
      organic contaminant, is degraded by 98% within 60 min under conditions of 50 mA,
      1 g/L Pd/MNPs (5 wt% Pd), pH 3 and 20 mg/L initial concentration. The degradation
      rate peaks at pH 3, increases with increasing Pd loading and electric current and
      decreases with increasing initial concentration. A distinct mechanism, reductive
      dissolution of solid Fe(III) in Fe3O4 by atomic H chemisorbed on Pd surface, is
      responsible for Fe(2+) production from Pd/MNPs. The efficiency of phenol
      degradation can be sustained at the same level for ten times of repeated
      treatment using the Pd/MNPs catalyst. The variations of main crystal structure
      and magnetic property of catalysts are minimal after treatment, but low
      concentrations of Pd leached, which needs further evaluation.

PMID- 24119932
TI  - A national audit of current cardiac device policies from radiotherapy centres
      across the UK.
AB  - AIMS: The number of patients with cardiac implantable electronic devices
      (permanent pacemakers and implantable cardioverter defibrillators) undergoing
      radiotherapy treatment is increasing. The aims of this audit were to establish
      current UK practice regarding the management of patients with implanted cardiac
      devices undergoing radiotherapy and to compare this practice with current 'gold
      standard' evidence-based guidelines. MATERIALS AND METHODS: All UK radiotherapy
      departments were contacted and asked to provide their current cardiac implantable
      electronic device policy or to indicate if there was no current policy. A
      proforma was created to analyse these policies and to compare with current best
      practice. RESULTS: In total, 47/67 (70%) radiotherapy departments responded and
      45 departmental policies were submitted; 31/45 (69%) policies defined the
      radiotherapy tolerance dose to permanent pacemakers and 14/45 (31%) defined the
      monitoring procedure for patients in line with current best practice. Only 5/45
      (11%) policies defined the radiotherapy tolerance dose to implantable
      cardioverter defibrillators and 12/45 (27%) defined the monitoring procedure in
      line with current best practice. CONCLUSION: Most UK cardiac device policies do
      not reflect current best evidence. Policies are based on research carried out in
      1994 by the American Association of Physicists in Medicine. This evidence does
      not account for advances in cardiac implantable electronic device technology.
      Further research is urgently needed to establish the effect of radiotherapy on
      these devices.

PMID- 24119933
TI  - Understanding the trans-generational consequences of prenatal stress.

PMID- 24119934
TI  - Predicting birth outcomes: together, mother and health care provider know best.
AB  - OBJECTIVE: To examine contributors to perceived risk in pregnancy and its utility
      in predicting lower birth weight and earlier delivery in conjunction with health
      care providers' assessment of obstetric risk. METHODS: 165 pregnant women at high
      (n=34) or low (n=131) obstetric risk completed assessments of perceived risk,
      stress, optimism, and health behaviors using well-validated instruments and
      measures designed for this study. Medical charts were abstracted for gestational
      age at delivery and birth weight. RESULTS: 40% of the sample perceived their risk
      status differently than their health care provider. Stress, poor reproductive
      history, provider assigned risk, and unhealthful behaviors were significant,
      independent predictors of perceived risk (R(2)=.37). The greatest difference in
      birth weight (p=.003) and gestational age (p=.05) was between women considered at
      low risk by both self and provider and women considered at high risk by both.
      Perceived risk improved prediction of adverse birth outcomes, especially lower
      birth weight, in women considered by providers to be at low risk. CONCLUSION:
      Women's perceptions of risk are an important contributor to prediction of birth
      outcomes, but the combination of information from both a woman and her health
      care provider is superior. Incorporating women's perceptions into obstetric risk
      determination may help to reduce the number of women identified as high risk who
      subsequently have a normal birth outcome (false positives), and more importantly,
      the number of women considered to be at low risk who ultimately experience an
      adverse outcome (false negatives).

PMID- 24119936
TI  - The association between perceived emotional support, maternal mood, salivary
      cortisol, salivary cortisone, and the ratio between the two compounds in response
      to acute stress in second trimester pregnant women.
AB  - OBJECTIVE: Little is known about the effect of social support on the reactivity
      of the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy. Moreover, when
      investigating the HPA axis most studies do not consider the activity of 11beta
      hydroxysteroid dehydrogenase type 2 (11beta-HSD2), an enzyme within the salivary
      glands that inactivates cortisol to cortisone. This study explores the
      association between perceived emotional support and the maternal psychobiological
      stress response to a standardized naturalistic stressor by assessing maternal
      mood and the reactivity of salivary cortisol (SalF), salivary cortisone (SalE),
      and the SalE/(E+F) ratio as a marker of 11beta-HSD2 activity. METHODS: Repeated
      saliva samples and measures of maternal mood were obtained from 34 healthy second
      trimester pregnant women undergoing amniocentesis which served as a psychological
      stressor. The pregnant women additionally responded to a questionnaire of
      perceived emotional support and provided sociodemographic (e.g., maternal
      educational degree) and pregnancy-specific data (e.g., planned versus unplanned
      pregnancy). RESULTS: Perceived emotional support neither showed a significant
      effect on mood nor on the SalF or SalE response to stress. However, a moderately
      strong positive association was found between perceived emotional support and
      SalE/(E+F) (r=.49). Additionally, the final regression analysis revealed a
      significant negative relationship between educational degree, planned/unplanned
      pregnancy and SalE/(E+F). CONCLUSION: Findings suggest a higher metabolization of
      cortisol to cortisone in pregnant women with higher emotional support. In
      contrast, higher maternal education and unplanned pregnancy appear to be
      associated with decreased salivary 11beta-HSD2 activity. The current study
      emphasizes the importance of taking the activity of 11beta-HSD2 into account when
      examining SalF.

PMID- 24119935
TI  - Ambulatory assessments of psychological and peripheral stress-markers predict
      birth outcomes in teen pregnancy.
AB  - OBJECTIVE: Pregnant adolescents have high rates of poor birth outcomes, but the
      causes are unclear. We present a prospective, longitudinal study of pregnant
      adolescents assessing associations between maternal psychobiological stress
      indices and offspring gestational age at birth and birthweight. METHOD: Healthy
      nulliparous pregnant adolescents were recruited (n=205) and followed during
      pregnancy. Ambulatory assessments over 24h of perceived psychological stress
      (collected every 30 min) and salivary cortisol (6 samples) and a summary
      questionnaire, the Perceived Stress Scale, were collected at three time points
      (13-16, 24-27, and 34-37 gestational weeks). Corticotropin-releasing hormone, C
      reactive protein, and interleukin 6 were assayed from blood taken at the latter 2
      sessions. A final sample of 119 participants was selected for analyses. RESULTS:
      The ambulatory assessment of perceived psychological stress was positively
      correlated with the Perceived Stress Scale (r=.20, p=.03) but neither was
      associated with any of the biological assays (all ps>.20). Based on backward
      selection regression models that included all stress variables and relevant
      covariates, the ambulatory assessments of perceived psychological stress and
      cortisol - though not the Perceived Stress Scale - were negatively associated
      with gestational age at birth (F(4, 107)=3.38, p=.01) while cortisol was
      negatively related to birthweight (F(5, 107)=14.83, p<.0001). CONCLUSIONS:
      Targeted interventions to reduce psychological and biological indicators of
      heightened stress during pregnancy may have positive public health benefits for
      the offspring given the associations of shortened gestation and lower birthweight
      with risk for poor mental and physical health outcomes.

PMID- 24119937
TI  - Physiological reactivity of pregnant women to evoked fetal startle.
AB  - OBJECTIVE: The bidirectional nature of mother-child interaction is widely
      acknowledged during infancy and childhood. Prevailing models during pregnancy
      focus on unidirectional influences exerted by the pregnant woman on the
      developing fetus. Prior work has indicated that the fetus also affects the
      pregnant woman. Our objective was to determine whether a maternal
      psychophysiological response to stimulation of the fetus could be isolated.
      METHODS: Using a longitudinal design, an airborne auditory stimulus was used to
      elicit a fetal heart rate and motor response at 24 (n=47) and 36 weeks (n=45) of
      gestation. Women were blind to condition (stimulus versus sham). Maternal
      parameters included cardiac (heart rate) and electrodermal (skin conductance)
      responses. Multilevel modeling of repeated measures with 5 data points per second
      was used to examine fetal and maternal responses. RESULTS: As expected, compared
      to a sham condition, the stimulus generated a fetal motor response at both
      gestational ages, consistent with a mild fetal startle. Fetal stimulation was
      associated with significant, transient slowing of maternal heart rate coupled
      with increased skin conductance within 10s of the stimulus at both gestational
      ages. Nulliparous women showed greater electrodermal responsiveness. The
      magnitude of the fetal motor response significantly corresponded to the maternal
      skin conductance response at 5, 10, 15, and 30s following stimulation.
      CONCLUSION: Elicited fetal movement exerts an independent influence on the
      maternal autonomic nervous system. This finding contributes to current models of
      the dyadic relationship during pregnancy between fetus and pregnant woman.

PMID- 24119938
TI  - Is there a viability-vulnerability tradeoff? Sex differences in fetal
      programming.
AB  - OBJECTIVE: In this paper we evaluate the evidence for sex differences in fetal
      programming within the context of the proposed viability-vulnerability tradeoff.
      METHODS: We briefly review the literature on the factors contributing to primary
      and secondary sex ratios. Sex differences in fetal programming are assessed by
      summarizing previously published sex difference findings from our group (6
      studies) and also new analyses of previously published findings in which sex
      differences were not reported (6 studies). RESULTS: The review and reanalysis of
      studies from our group are consistent with the overwhelming evidence of
      increasing risk for viability among males exposed to environmental adversity
      early in life. New evidence reported here support the argument that females,
      despite their adaptive agility, also are influenced by exposure to early
      adversity. Two primary conclusions are (i) female fetal exposure to
      psychobiological stress selectively influences fear/anxiety, and (ii) the effects
      of female fetal exposure to stress persist into preadolescence. These persisting
      effects are reflected in increased levels of anxiety, impaired executive function
      and neurological markers associated with these behaviors. CONCLUSIONS: A tacit
      assumption is that females, with their adaptive flexibility early in gestation,
      escape the consequences of early life exposure to adversity. We argue that the
      consequences of male exposure to early adversity threaten their viability,
      effectively culling the weak and the frail and creating a surviving cohort of the
      fittest. Females adjust to early adversity with a variety of strategies, but
      their escape from the risk of early mortality and morbidity has a price of
      increased vulnerability expressed later in development.

PMID- 24119939
TI  - Maternal positive affect over the course of pregnancy is associated with the
      length of gestation and reduced risk of preterm delivery.
AB  - OBJECTIVE: The association between maternal psychological state during pregnancy
      and birth outcomes is well established. The focus of previous studies has been on
      the potentially detrimental consequences of maternal stress on pregnancy and
      birth outcomes, particularly shortened gestation and increased risk of preterm
      birth. Despite a growing literature linking positive affect with favorable health
      outcomes this construct has received little attention in the context of
      pregnancy. Therefore, in the current study, we tested the hypothesis that
      maternal positive affect during pregnancy is associated with beneficial
      consequences in terms of increased length of gestation and reduced risk of
      preterm birth above that of the absence of stress. METHODS: In 169 pregnant women
      maternal positive affect and perceived stress were serially assessed at 15.2 +/-
      0.9 weeks (T1; mean +/- SD), 19.7 +/- 0.9 weeks (T2) and 30.7 +/- 0.7 weeks (T3)
      gestation. Pregnancy and birth outcomes were abstracted from the medical record.
      RESULTS: Higher maternal positive affect and a steeper increase in maternal
      positive affect over pregnancy were positively associated with length of
      gestation (p<.05) and reduced risk of preterm delivery (p<.01), whereas maternal
      perceived stress was not significantly associated with shorter length of
      gestation (p>.10). CONCLUSIONS: These findings suggest that maternal positive
      affect may be beneficial for outcomes related to the length gestation, and that
      this effect cannot be accounted for by the lower stress levels associated with
      higher positive affect. Interventions to increase maternal positive affect may be
      beneficial for fetal development.

PMID- 24119940
TI  - Maternal prenatal symptoms of depression and down regulation of placental
      monoamine oxidase A expression.
AB  - OBJECTIVE: Maternal prenatal symptoms of depression and anxiety have been
      associated with altered neurodevelopmental outcomes in the child. These effects
      may be mediated in part by altered placental function, with increased fetal 5
      hydroxytryptamine (5-HT) exposure being one possible mechanism. The current study
      aimed to determine whether maternal symptoms of depression or anxiety were
      associated with decreased placental expression of monoamine oxidase A (MAO A),
      the enzyme which metabolises 5-HT into 5-hydroxyindoleacetic acid. The
      localisation of MAO A in the placenta was also investigated. METHODS: Pregnant
      women were recruited one day prior to elective caesarean and assessed using
      psychometric tests for symptoms of depression (Edinburgh Depression Scale) and
      anxiety (Spielberger State/Trait Index). Villous trophoblast tissue was extracted
      from each placenta and used for subsequent gene expression analysis (N=62).
      Localisation was studied using immunohistochemistry, with a specific polyclonal
      antibody. RESULTS: Increasing symptoms of maternal depression were associated
      with a reduction in placental MAO A expression (r=-0.339, p=0.007, N=62). There
      was a trend for a similar correlation with symptoms of maternal trait anxiety,
      but not with state anxiety. MAO A was localised to the syncytiotrophoblast, the
      tissue between maternal and fetal blood. CONCLUSIONS: These findings support the
      hypothesis that maternal mood is associated with altered placental function. A
      reduction in placental MAO A expression is consistent with a subsequent increase
      in fetal exposure to 5-HT.

PMID- 24119941
TI  - Maternal generalized anxiety disorder during pregnancy and fetal brain
      development: a comparative study on cord blood brain-derived neurotrophic factor
      levels.
AB  - OBJECTIVES: The study aimed to investigate whether maternal GAD during pregnancy
      affects fetal circulating brain-derived neurotrophic factor (BDNF), which plays
      important roles in neuronal development, by comparing cord blood BDNF levels in
      newborn infants of women with and without GAD. METHODS: Study sample included 19
      women with GAD and 25 women without any psychiatric disorder. GAD and other
      psychiatric diagnoses were screened by means of the Structured Clinical Interview
      for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
      The blood sample for the determination of BDNF level was obtained from the
      umbilical cord during delivery. RESULTS: Cord blood BDNF levels in newborn
      infants of healthy women were approximately two-fold compared to newborn infants
      of women with GAD, and the difference was statistically significant. The duration
      of GAD during pregnancy was the only variable correlating with cord blood BDNF
      levels. CONCLUSIONS: The study results imply that prolonged maternal GAD during
      pregnancy may negatively influence neurodevelopment of the fetus through lower
      levels of circulating BDNF.

PMID- 24119942
TI  - Prenatal programming of emotion regulation: neonatal reactivity as a differential
      susceptibility factor moderating the outcome of prenatal cortisol levels.
AB  - OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) activation during pregnancy is
      linked to dysfunctional behavioral outcomes in the offspring. According to
      Belsky's differential susceptibility hypothesis, individuals vary regarding their
      developmental plasticity. Translating the differential susceptibility hypothesis
      to the field of fetal programming, we hypothesize that infants' temperament, as
      the constitutionally based reactivity to stimulation, moderates prenatal
      environmental effects on postnatal emotion regulation. METHODS: Maternal HPA axis
      activity and stress-reactivity during pregnancy was estimated, by measuring
      cortisol concentrations in saliva, collected at 0, 30, 45 and 60 min after
      awakening and in blood, collected during a laboratory stress test (Trier Social
      Stress Test), respectively. Newborns reactivity to stimulation was evaluated
      between postnatal day 10 and 14 using the Neonatal Intensive Care Unit Network
      Neurobehavioral Scale. Infant's self-quieting-activities, as an indicator of
      emotion regulation, were evaluated at the age of six months during the still face
      paradigm. RESULTS: Maternal cortisol reactivity to stress during pregnancy was
      associated with infant's emotion regulation at the age of six months. Whereas
      cortisol levels after awakening in mid and late pregnancy were not associated
      with emotion regulation. Furthermore, regression analyses revealed that in
      interaction with neonatal reactivity, both, prenatal maternal HPA activity as
      well as prenatal maternal HPA reactivity to stress predicted emotion regulation.
      CONCLUSION: The findings indicate that newborns' reactivity to stimulation is
      moderating the association between prenatal exposure to maternal glucocorticoids
      and emotion regulation in infancy. Data suggests that temperamental
      characteristics of the newborn are a relevant differential susceptibility factor
      with regard to prenatal effects on emotion regulation.

PMID- 24119944
TI  - Personality traits, defense mechanisms and hostility features associated with
      somatic symptom severity in both health and disease.
AB  - OBJECTIVE: Somatic symptoms are widespread in clinical practice. The association
      of somatic symptom severity with impaired health status holds both when symptoms
      are medically unexplained and when they are medically explained. The role of
      personality dimensions in the formation of somatic symptoms in patients with
      established, chronic diseases when compared to healthy participants had not been
      investigated prior to this study. METHODS: In samples of 411 healthy subjects and
      810 participants with any of 9 established, chronic medical conditions, we
      measured psychological distress (SCL-90-R), personality traits (Zuckerman-Kuhlman
      Personality Questionnaire), defensive profiles (Defense Style Questionnaire),
      individual defenses (Life Style Index) and hostility features (Hostility and
      Direction of Hostility Questionnaire). Hierarchical multivariate models were used
      to assess the independent associations between personality dimensions and somatic
      symptom severity in both samples. The SCL-90-R somatization scale served as the
      outcome variable. RESULTS: In both samples, older age, less education, higher
      neuroticism, adoption of the displacement defense and depressive symptoms were
      independently and positively associated with somatic symptom severity. Higher
      somatic symptom severity was also associated with more "introverted" features
      (i.e., the self-sacrificing defensive style and self-criticism) among
      participants with established, chronic medical conditions. CONCLUSIONS: These
      data suggest that similar personality traits and defense mechanisms are
      associated with somatic symptom severity in health and disease, indicating that
      somatic symptoms are not simply consequences of having a medical condition. The
      specific associations of the self-sacrificing defensive profile and self
      criticism with somatic symptom severity in the patient sample may have important
      clinical implications.

PMID- 24119943
TI  - Predictive validity and clinical utility of DSM-5 Somatic Symptom Disorder:
      prospective 1-year follow-up study.
AB  - OBJECTIVE: To compare the predictive validity and clinical utility of DSM-IV
      somatoform disorders and DSM-5 Somatic Symptom Disorder (SSD) at 12-month follow
      up. METHODS: In a sample of psychosomatic inpatients (n=322, mean age=45.6 years
      (SD 10.0), 60.6% females) we prospectively investigated DSM-IV somatoform
      disorders and the DSM-5 diagnosis of SSD plus a variety of psychological
      characteristics, somatic symptom severity, and health-related quality of life at
      admission, discharge, and follow-up. RESULTS: DSM-IV diagnoses and DSM-5 SSD
      similarly predicted physical functioning at follow-up; SSD also predicted mental
      functioning at follow-up. Bodily weakness, intolerance of bodily complaints,
      health habits, and somatic attribution at admission were significant predictors
      of physical functioning at follow-up. The change in physical functioning during
      inpatient therapy was a significant predictor for the course of physical
      functioning until follow-up. CONCLUSIONS: Psychological symptoms appear to be
      predictively valid diagnostic criteria for the 12-month functional outcome in
      patients with SSD. Mental functioning can be better predicted by the DSM-5
      diagnosis than by DSM-IV diagnoses. Not the change in single psychological
      features but in physical functioning during the treatment interval predicted the
      change in physical functioning until follow-up.

PMID- 24119945
TI  - Association of costs with somatic symptom severity in patients with medically
      unexplained symptoms.
AB  - OBJECTIVE: To analyse the association of direct and indirect costs in patients
      with medically unexplained symptoms (MUS) with somatic symptom severity (SSS).
      METHODS: A cross-sectional cost analysis for retrospective 6 months was conducted
      in 294 primary care patients with MUS. Health care utilisation and loss of
      productivity were measured by questionnaires. SSS was measured using the "Patient
      Health Questionnaire 15" (PHQ-15). Direct and indirect costs and the association
      of costs with SSS were analysed via multiple linear regression analysis. RESULTS:
      Patients with MUS had average 6-month direct costs of 1098 EUR and indirect costs
      of 7645 EUR. For direct costs, outpatient physician visits were the most
      expensive single cost category (36%), followed by pharmaceuticals (25%) and
      hospital stays (19%). Indirect costs were predominantly caused by productivity
      reduction at work (56%) followed by early retirement (29%) and acute sickness
      absence (14%). As compared to mild SSS, moderate SSS was not significantly
      associated with direct, but with indirect costs (+2948 EUR; p<.001); severe SSS
      was associated with increased direct cost (+658 EUR; p=.001) and increased
      indirect costs (+4630 EUR; p<.001). Age was positively associated with direct
      cost (+15 EUR for each additional year; p=.015) as well as indirect cost (+104
      EUR for each additional year; p<.001). CONCLUSIONS: MUS are associated with
      relevant direct and even much higher indirect costs that strongly depend on SSS.

PMID- 24119946
TI  - Caregiver burden and disability in somatization disorder.
AB  - OBJECTIVE: Authors assessed disability and caregiver burden in patients with
      somatization disorder (SOM-D), and compared it with that in patients with
      schizophrenia and chronic depression. METHODS: The sample consisted of 30
      patients diagnosed as SOM-D as per ICD 10 Diagnostic Criteria for Research (ICD
      10-DCR), and 30 age- and gender-matched patients each of schizophrenia and
      depression, who served as comparison groups. Disability and caregiver burden were
      assessed using WHO's Disability Assessment Schedule (WHO-DAS) and the Family
      Burden Assessment Schedule (FBAS) respectively. Functioning and severity of
      illness were assessed on the Global Assessment of Functioning scale (GAF) and
      Clinical Global Impression scale (CGI) respectively. RESULTS: Severity of illness
      in patients with SOM-D was comparable to that in the comparison groups. Patients
      with SOM-D scored higher on total disability on WHO-DAS than the patients with
      schizophrenia and depression, though scores on family burden were comparable.
      Disability in patients with SOM-D was more in females, less educated, older and
      those working at home, compared to the other demographic groups. CONCLUSION:
      Patients with SOM-D suffer considerable disability due to illness and impose
      significant burden on their caregivers, comparable to that seen in severe mental
      illnesses like schizophrenia and chronic depression.

PMID- 24119948
TI  - Posttraumatic stress disorder and odds of major invasive procedures among U.S.
      Veterans Affairs patients.
AB  - OBJECTIVES: Although individuals with posttraumatic stress disorder (PTSD) are at
      heightened risk for several serious health conditions, research has not examined
      how having PTSD impacts receipt of invasive procedures that may alleviate these
      problems. We examined whether PTSD, after controlling for major depression, was
      associated with odds of receiving common types of major invasive procedures, and
      whether race, ethnicity, and gender was associated with odds of procedures.
      METHODS: Veterans Health Administration patients with PTSD and/or depression were
      age-matched with patients without these disorders. The odds of invasive hip/knee,
      digestive system, coronary artery bypass graft/percutaneous coronary intervention
      (CABG/PCI), and vascular procedures during FY2006-2009 were modeled for the full
      sample of 501,489 patients and for at-risk subsamples with medical conditions
      alleviated by the procedures examined. RESULTS: Adjusting for demographic
      covariates and medical comorbidity, PTSD without depression was associated with
      decreased odds of all types of procedures (odds ratios [OR] range 0.74-0.82), as
      was depression without PTSD (OR range 0.59-0.77). In analyses of at-risk
      patients, those with PTSD only were less likely to undergo hip/knee (OR=0.78) and
      vascular procedures (OR=0.73) but not CABG/PCI. African-Americans and women at
      risk patients were less likely to undergo hip/knee, vascular, and CABG/PCI
      procedures (OR range 0.31-0.82). CONCLUSION: With the exception of CABG/PCI among
      at-risk patients, Veterans with PTSD and/or depression were less likely to
      undergo all types of procedures examined. Future studies should examine the
      reasons for this disparity and whether it is associated with subsequent adverse
      outcomes.

PMID- 24119949
TI  - Ethical issues concerning the recruitment of university students as research
      subjects.
AB  - OBJECTIVE: To discuss the ethical issues in the recruitment of university
      students as research subjects. METHODS: Narrative review and discussion. RESULTS:
      The recruitment and inclusion of students in university research projects raise
      ethical issues specific to this population. Students may be required or coerced
      to participate, receive course credits for their participation, and their privacy
      may be violated. Some ethically questionable procedures are standard practice at
      some universities, and endorsed by their institutional review boards and
      faculties. Some changes will not be easy to achieve because this implies a change
      of organization of research and will affect funding and output. CONCLUSION: The
      authors call for international standards to be set for research with students,
      that are in line with applicable standards in research with other subjects, such
      as medically ill patients, on which researchers, members of institutional review
      boards and editors can base their policies, opinions and decisions.

PMID- 24119947
TI  - Emotion suppression and mortality risk over a 12-year follow-up.
AB  - OBJECTIVE: Suppression of emotion has long been suspected to have a role in
      health, but empirical work has yielded mixed findings. We examined the
      association between emotion suppression and all-cause, cardiovascular, and cancer
      mortality over 12 years of follow-up in a nationally representative US sample.
      METHODS: We used the 2008 General Social Survey-National Death Index (GSS-NDI)
      cohort, which included an emotion suppression scale administered to 729 people in
      1996. Prospective mortality follow up between 1996 and 2008 of 111 deaths (37 by
      cardiovascular disease, 34 by cancer) was evaluated using Cox proportional
      hazards models adjusted for age, gender, education, and minority race/ethnicity.
      RESULTS: The 75th vs. 25th percentile on the emotional suppression score was
      associated with hazard ratio (HR) of 1.35 (95% Confidence Interval [95% CI]=1.00,
      1.82; P=.049) for all-cause mortality. For cancer and cardiovascular disease
      mortality, the HRs were 1.70 (95% CI=1.01, 2.88, P=.049) and 1.47 (95% CI=.87,
      2.47, P=.148) respectively. CONCLUSIONS: Emotion suppression may convey risk for
      earlier death, including death from cancer. Further work is needed to better
      understand the biopsychosocial mechanisms for this risk, as well as the nature of
      associations between suppression and different forms of mortality.

PMID- 24119950
TI  - Commentary: On the ethics of recruiting students--and patients.

PMID- 24119951
TI  - Ethical issues concerning the recruitment of university students as research
      subjects: reply to Lumley and Jasinski.

PMID- 24119952
TI  - Younger children's nursing students are uniquely placed to provide emotional care
      for young people in hospital and promote for them a sense of normalcy.
AB  - OBJECTIVES: To highlight the emotional impact of being in the hospital for young
      people and to explore the impact of the care by younger student nurses on
      promoting a sense of "normalcy" for them. BACKGROUND: Adolescence is strongly
      influenced by peer relationships and is a unique period in life that requires the
      achievement of many developmental tasks. An important task of adolescent is
      developing relationships with peers and feeling part of a recognised peer group.
      Young people prefer engaging in conversation with people of their own age because
      they feel less likely to be judged by their peers. DESIGN: Heideggerian
      hermeneutic phenomenological study. METHOD: A Heideggerian phenomenological study
      was undertaken. Individual unstructured interviews were conducted with eleven
      younger student nurses (aged l7 years and 5 months-l8 years and 11 months) and
      nine young people with a chronic illness (aged 13 years and 7 months-18 years and
      1 month). The data was collected in 2009. RESULTS: Young people in the hospital
      with a chronic illness experienced moments in time when they had nothing to think
      about but the business of getting better. During unique caring interactions,
      younger children's nursing students were able to help them temporarily forget
      about their illness and promote for them a sense of normalcy. CONCLUSIONS:
      Younger children's nursing students are in a unique position to engage in
      ontological caring interactions with the young people due to their similarity in
      age and stage of development. They are uniquely placed to help the young people
      reintegrate back into their known "lifeworlds" and promote for them a sense of
      "normalcy". RELEVANCE TO CLINICAL PRACTICE: Clinical staff need to be alerted to
      the emotional distress caused to young people during long periods of time in the
      hospital. Practitioners and nurse educators should be facilitating younger
      student nurses to interact with the young people in a therapeutic way and the
      care delivered to young people in the hospital should promote a sense of normalcy
      for them.

PMID- 24119953
TI  - Student nurses perceptions of spirituality and competence in delivering spiritual
      care: a European pilot study.
AB  - BACKGROUND: Spiritual care is expected of nurses, but it is not clear how
      undergraduates can achieve competency in spiritual care at point of registration
      as required by nursing/midwifery regulatory bodies. AIMS: To describe
      undergraduate nurses'/midwives' perceptions of spirituality/spiritual care, their
      perceived competence in delivering spiritual care, and to test out the proposed
      method and suitability of measures for a larger multinational follow-on study.
      DESIGN: Cross-sectional, multinational, descriptive survey design. METHODS:
      Author administered questionnaires were completed by 86% of the intended
      convenience sample of 618 undergraduate nurses/midwives from 6 universities in 4
      European countries in 2010. RESULTS: Students held a broad view of
      spirituality/spiritual care and considered themselves to be marginally more
      competent than not in spiritual care. They were predominantly Christian and
      reported high levels of spiritual wellbeing and spiritual attitude and
      involvement. The proposed method and measures were appropriate and are being used
      in a follow-on study. CONCLUSIONS: The following are worthy of further
      investigation: whether the pilot study findings hold in student samples from more
      diverse cultural backgrounds; whether students' perceptions of spirituality can
      be broadened to include the full range of spiritual needs patients may encounter
      and whether their competence can be enhanced by education to better equip them to
      deliver spiritual care; identification of factors contributing to acquisition of
      spiritual caring skills and spiritual care competency.

PMID- 24119954
TI  - Reprint of: Evaluation of next generation mtGenome sequencing using the Ion
      Torrent Personal Genome Machine (PGM).
AB  - Insights into the human mitochondrial phylogeny have been primarily achieved by
      sequencing full mitochondrial genomes (mtGenomes). In forensic genetics (partial)
      mtGenome information can be used to assign haplotypes to their phylogenetic
      backgrounds, which may, in turn, have characteristic geographic distributions
      that would offer useful information in a forensic case. In addition and perhaps
      even more relevant in the forensic context, haplogroup-specific patterns of
      mutations form the basis for quality control of mtDNA sequences. The current
      method for establishing (partial) mtDNA haplotypes is Sanger-type sequencing
      (STS), which is laborious, time-consuming, and expensive. With the emergence of
      Next Generation Sequencing (NGS) technologies, the body of available mtDNA data
      can potentially be extended much more quickly and cost-efficiently. Customized
      chemistries, laboratory workflows and data analysis packages could support the
      community and increase the utility of mtDNA analysis in forensics. We have
      evaluated the performance of mtGenome sequencing using the Personal Genome
      Machine (PGM) and compared the resulting haplotypes directly with conventional
      Sanger-type sequencing. A total of 64mtGenomes (>1 million bases) were
      established that yielded high concordance with the corresponding STS haplotypes
      (<0.02% differences). About two-thirds of the differences were observed in or
      around homopolymeric sequence stretches. In addition, the sequence alignment
      algorithm employed to align NGS reads played a significant role in the analysis
      of the data and the resulting mtDNA haplotypes. Further development of alignment
      software would be desirable to facilitate the application of NGS in mtDNA
      forensic genetics. 

PMID- 24119955
TI  - Late toxicity and cosmetic outcomes related to interstitial multicatheter
      brachytherapy for partial breast irradiation.

PMID- 24119956
TI  - Association between acute sympathetic response, early onset vasospasm, and
      delayed vasospasm following spontaneous subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is accompanied by a marked acute sympathetic
      response, and evidence exists for sympathetic participation in the development of
      cerebral vasospasm (VS). The purpose of this observational investigation was to
      assess the association between acute central catecholaminergic activity, early VS
      and delayed VS following SAH. SAH grade 3-5 patients who received
      ventriculostomy, and in whom bilateral temporal transcranial insonation was
      performed, were enrolled. Cerebrospinal fluid (CSF) was sampled (<48 hours) and
      assayed for catecholamines, which were correlated to measures of early and
      delayed sonographic anterior circulation VS. Clinical independent predictors of
      early VS included age (odds ratio .946 [95% confidence interval .902-.991]), CT
      scan score (4.27 [1.30-14.0]) and neurogenic cardiomyopathy (6.5 [1.24-34.1]).
      Age (.925 [.859-.996]) and CT scan score (8.30 [1.33-5.17]) also independently
      predicted delayed VS. Any early VS independently predicted conventionally defined
      delayed VS (10.9 [2.64-45.0]), and severe delayed VS was independently predicted
      by any early VS (9.87 [2.45-39.7]) and by conventionally defined early VS (12.3
      [2.80-54.1]). The norepinephrine:3,4-dihydroxyphenylglycol ratio (NE/DHPG)
      independently predicted severe delayed VS (3.38 [1.01-11.35]), for which DHPG was
      a negative predictor (.356 [.151-.839]). Epinephrine was a negative predictor of
      any early VS (.574 [.357-.921]), any delayed VS (.372 [.158-.875]), and delayed
      conventional VS (.402 [.200-.807]). Early and delayed VS appear to be related
      processes that are generally unrelated to the acute central sympathetic response
      following SAH. The one exception may be severe delayed VS which may be associated
      with noradrenergic activation.

PMID- 24119958
TI  - [Importance of clinical trial design and standardized implementation in
      ophthalmology].
AB  - Clinical trial is an important medical research method, as well as the bridge of
      translational medicine. The results of scientific evidences are useful to make
      clinical practice guidelines. At present,much experience of carrying out
      ophthalmology clinical trials has been obtained and achieved, but there are still
      some scientific, practical and ethical problems to be solved,because of their
      impact on the authenticity and reliability of the results. Therefore, attaching
      great importance to design of the clinical research and implement of the
      standardization would be the goal and the development direction. Clinical trial
      design rely on objective, follow international design principles on the
      ethics,randomization, blinding and placebo setting. During the trial
      implementation, personnel training,project management and monitoring would help
      to reduce protocol deviation and ensure data authenticity. 

PMID- 24119959
TI  - [The development and importance of molecular diagnosis in hereditary retinal
      diseases].
AB  - Hereditary retinal disease(HRD) is a group of retinal degenerations seen
      frequently at clinic,which can lead to severe visual impairments or even
      blindness.Identifying genetic causes and developing advanced and applicable
      molecular diagnostic tools for HRD is essential to lower the prevalence of HRD,
      and to find the therapeutic method of HRD. HRD is known to be both clinically and
      genetically heterogeneous. The large number of causative genes together with the
      limitation of routine technique hinder the investigators from further
      investigating the genetic causes of HRD. Targeted genes capture with next
      generation high throughput sequencing yield high sensitivity and speed for
      mutation detection.When compared with traditional techniques, targeted sequencing
      presents tremendous advantages. Therefore, the development of a powerful
      molecular diagnostic platform for HRD aims to improve the detection rate of
      causative genes/mutations in HRD patients, to further investigate the genetic
      causes for HRD, to better understand the pathological basis of HRD, and to
      promote the fast development of molecular diagnosis in China. Meanwhile, it will
      have significance for the clinical and prenatal diagnosis of HRD, and thus
      providing rationale for gene therapy on HRD. 

PMID- 24119957
TI  - Spectrum of imaging appearances in Australian children with central nervous
      system hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder
      characterised by the proliferation and infiltration of lymphocytes and
      histiocytes. Central nervous system (CNS) infiltration is particularly
      devastating. Neuroradiological findings have been reported predominantly as
      individual case reports due to the rarity of the condition. To our knowledge
      there have been no published studies of imaging in Australian patients. This
      study aimed to retrospectively describe and illustrate the MRI appearances of CNS
      involvement by HLH in a cohort of seven Australian children from two paediatric
      centres between 2000 and 2011. MRI appearances demonstrate intersubject and
      intrasubject variability over time, likely reflecting the severity of CNS
      infiltration and associated demyelination. Familiarity with MRI patterns is
      important for assessing and monitoring disease activity. 

PMID- 24119960
TI  - [Choroidal thickness after half-dose verteporfin photodynamic therapy in chronic
      central serous chorioretinopathy].
AB  - OBJECTIVE: To observe the choroidal thickness in eyes with chronic central serous
      chorioretinopathy(CSC) after half-dose photodynamic therapy(PDT). METHODS: Case
      series study. Consecutive 30 patients (35 eyes) with chronic CSC admitted from
      October 2010 to October 2011 in Zhongshan Ophthalmic Center were recruited in
      this study. Optical coherence tomography(OCT),fundus fluorescein angiography,
      indocyanine green angiography (ICGA) were performed in each patient to confirm
      the diagnosis. ICGA-guided PDT was performed in each patient. Choroidal thickness
      at subfoveal and 1500 um superior, inferior, nasal and temporal to the fovea were
      measured before PDT, 1, 3 and 6 months after PDT using enhanced depth imaging
      OCT. Data were analyzed with one-way repeated measures ANOVA and LSD-t test when
      pairwise comparison was needed. RESULTS: Thirty patients, aged from 33 to 66
      years old, including 26 males and 4 females (gender ratio 6.5: 1) were recruited.
      Subfoveal choroidal thickness (SFCT) in chronic CSC eyes was (435.54 +/- 102.91)
      um at baseline,which decreased significantly to (373.63 +/- 106.01) um, (360.69
      +/- 111.06) um and (369.00 +/- 108.12) um at 1 month, 3 months and 6 months after
      PDT respectively (F = 108.34, P < 0.01). At 6 months after PDT, SFCT was slightly
      thicker than that at the 3(rd) month,but no statistical significance was noted
      (LSD-t test: P > 0.05). The changing trends of choroidal thickness at the other 4
      measuring points were similar to that of the SFCT. CONCLUSION: Choroidal
      thickness is reduced within 6 months post PDT in chronic CSC eyes.

PMID- 24119961
TI  - [Clinical analysis of acute zonal occult outer retinopathy masquerading as optic
      neuropathy].
AB  - OBJECTIVE: To analyze the clinical features of acute zonal occult outer
      retinopathy (AZOOR) and the reasons for misdiagnosing as optic neuropathy or
      intracranial lesions. METHODS: Case series study. Twenty patients (23 eyes) who
      were all initially diagnosed as optic neuropathy or intracranial lesions were
      recruited in the ophthalmologic department of Beijing Tongren Hospital from
      November 2003 to June 2012, but they were ultimately diagnosed as AZOOR after the
      examinations including regular eye examination, fundus fluorescein angiography
      (FFA), optical coherence tomography (OCT), automatic perimetry, flash
      electroretinogram (F-ERG),multifocal electroretinogram (mfERG),systemic
      rheumatism immunological examination and neuroimaging. RESULTS: These 20 patients
      with an average age of 32.9 years (range 15 to 55 years) consisted of 17 females
      (85%) and 3 males (15.0%). Among them, 17 patients (85.0%) were affected
      unilaterally, while 3 patients (15.0%) were affected bilaterally. Sixteen of 23
      eyes (69.6%) had myopia. Ten eyes (58.8%) showed relative afferent papillary
      defect. Inflammatory response was not found by slit lamp and fundus examination.
      Besides the other abnormal fundus changes of high myopia, fundus angioid streaks
      were found in 4 eyes and retinal pigment epithelium dystrophy was found in 3 eyes
      by fundus examination. FFA revealed that there was mild fluorescein leakage
      around the retinal vascular arch in one eye. The patterns of visual field detect
      in these patients were various, while temporal scotoma and blind spot enlargement
      were most common. Twelve of 14 patients who had been performed F-ERG showed
      abnormal F-ERG. mfERG of all patients showed the decreased amplitude densities of
      the retina in accordance with the areas of visual field defect. IS/OS layer of 17
      patients who went through OCT examination were found abnormal in the
      corresponding areas of visual field defect. Neuroimaging examination revealed
      there was nothing abnormal in the patients who were diagnosed as intracranial
      lesions. Immunological parameters in these patients were almost normal except for
      one patient with an increased level of rheumatoid factor. CONCLUSIONS: AZOOR
      patients in this study rarely has ocular or systemic inflammatory. AZOOR occurs
      predominantly in the unilateral eye of young female patients, and are easily
      misdiagnosed as optic neuropathy due to the almost normal appearances of fundus.
      The examinations of retinal functional and morphological changes are the key to
      its diagnosis and differential diagnosis.

PMID- 24119962
TI  - [Diabetes self-management and its association with diabetic retinopathy in
      patients with type 2 diabetes].
AB  - OBJECTIVE: To investigate the association of diabetic self-management with the
      risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.
      METHODS: Cross-sectional study. Recruited patients with type 2 diabetes mellitus
      in the Desheng community of urban Beijing between November 2009 and May 2011. All
      patients were surveyed using a standardized questionnaire and underwent detailed
      ophthalmic examination. Patients were classified into DR group or diabetic
      without retinopathy (DWR) group according to the grading of fundus color
      photographs using the Early Treatment of Diabetic Retinopathy Study (ETDRS)
      standard grading protocol. In the DR group, proliferative diabetic retinopathy
      (PDR) was further defined. The overall levels of diabetes self-management in the
      study population were assessed and compared for the differences between DR and
      DWR, PDR and NPDR groups. RESULTS: One thousand one hundred patients with type 2
      diabetes mellitus were recruited. The prevalence of DR was 32.1% (353/1100) in
      the study population. Sixty-three percent (652/1035) of patients had glycated
      hemoglobin (HbA1c) level less than 7.0%. The majority of patients (85.4%,
      916/1072) conducted a diet control, 77.3% (827/1070) exercised, 56.0% (609/1088)
      monitored blood glucose regularly, 56.8% (416/733) detected HbA1c more than once
      every six months, 71.7% (762/1062) had ophthalmologic examination after the
      diagnosis of diabetes mellitus, and 47.9% (525/1097) had mydriatic check-up.
      Increased risk of DR was associated with longer duration of diabetes (more than
      10 years) (OR = 3.90, 95% CI:2.97-5.51, P < 0.05), higher HbA1c level of >= 7.0%
      (OR = 3.23, 95% CI:2.44-4.28, P < 0.05), insulin therapy (OR = 4.82, 95% CI:3.55
      6.57, P < 0.05), male gender (OR = 1.41, 95% CI:1.08-1.84, P < 0.05), lower level
      of education (OR = 1.90, 95% CI:1.39-2.62, P < 0.05), lower monthly income (OR =
      1.46, 95% CI:1.12-1.91, P < 0.05), lower obedience to diet control (OR = 1.72,
      95% CI:1.22-2.43, P < 0.05), no exercise (OR = 1.42, 95% CI:1.04-1.94, P < 0.05),
      change of therapeutic protocol during the last five years (OR = 1.78, 95% CI:1.32
      2.41, P < 0.05), and family history of diabetes (OR = 1.35, 95% CI:1.01-1.78, P <
      0.05). Increased risk of PDR was associated with the diagnosis age of diabetes
      (OR = 0.92, 95% CI:0.89-0.95, P < 0.05), longer duration of diabetes (more than
      10 years) (OR = 4.54, 95% CI:1.95-12.32, P < 0.05), and insulin therapy (OR =
      4.85, 95% CI:2.34-10.90, P < 0.05). In the multifactor logistic regression model,
      male gender (OR = 2.21, 95% CI:1.57-3.11, P < 0.05), lower level of education (OR
      = 1.98, 95% CI:1.33-2.94, P < 0.05), lower monthly income (OR = 1.66, 95% CI:1.15
      2.39, P < 0.05) ,longer duration of diabetes (more than 10 years) (OR = 2.46, 95%
      CI:1.77-3.41, P < 0.05) ,HbA1c >= 7.0% (OR = 2.24, 95% CI:1.64-3.07, P < 0.05)
      and insulin therapy (OR = 3.38, 95% CI:2.38-4.8, P < 0.05) were associated with
      higher risk of DR. The diagnosis age of diabetes (OR = 0.94, 95% CI:0.91-0.98, P
      < 0.05) and insulin therapy (OR = 3.49, 95% CI:1.47-8.27, P < 0.05) were
      associated with PDR. CONCLUSION: Higher risk of DR is associated with longer
      duration of diabetes,insulin therapy, higher HbA1c level, male gender, and lower
      level of education, whereas higher risk of DR is also associated with lower
      obedience to diet control and less exercise, which suggest that lower level of
      diabetic self-management increased the risk of DR.

PMID- 24119963
TI  - [Clinical characteristics of paraneoplastic retinopathy and optic neuropathy].
AB  - OBJECTIVE: To analyze the clinical characteristics of paraneoplastic retinopathy
      and optic neuropathy(PRON). METHODS: Case series study. Eight patients were
      enrolled from October 2006 to March 2012 visited in ophthalmology department, the
      People Liberation Army General Hospital. The patients were underwent a series of
      examinations, including fundus photography, visual electrophysiology, fundus
      fluorescein angiography, optic coherent tomography,fundus autofluorescent
      imaging, perimetry, ultrasonography, magnetic resonance imaging, spinal tap and
      cerebrospinal fluid test, paraneoplastic syndrome (PNS) antibody test. The
      patients were followed up in outpatient department and(or) by phone. The clinical
      manifestation,entity types, and treatment were analyzed. RESULTS: Of the eight
      patients, there were cancer associated retinopathy(CAR) 3 cases, bilateral
      diffuse uveal melanocytic proliferation (BDUMP) 2 cases and paraneoplastic optic
      neuropathy(PON) 3 cases. Five patients were detected the PNS antibodies and
      revealed three patients with positive results. As for the primary malignancy,four
      of the eight patients were lung carcinoma,others included invasive thymoma,
      kidney cancer, acute lymphocytic leukemia and cervical cancer, each for one case.
      All the patients complained vision blurring or progressive visual decrease. Other
      complaints included dark shadow in two patients, shimmering, dazzling, double
      vision and eye pain, each in one patient. One patient complained progressive
      decreased vision in both eyes prior to the diagnosis of lung cancer. Of the 16
      eyes of the eight patients, there were six patients with no light perception
      vision, five from light perception to 0.05, and other five with no less than 0.4
      vision, in the end of the follow up. Five patients were treated with steroid with
      unsatisfactory efficacy. CONCLUSIONS: Each entity of PRON has its own clinical
      characteristics. PRON especially BDUMP may be a pre-metastatic disease.

PMID- 24119964
TI  - [Correlation of optic retinal nerve fiber layer thickness and visual function in
      patients with nonproliferative diabetic retinopathy].
AB  - OBJECTIVES: To investigate the change of optic retinal nerve fiber layer (RNFL)
      thickness in nonproliferative diabetic retinopathy (NPDR) and to evaluate the
      correlation between the optic RNFL structural change and visual function.
      METHODS: A cross-sectional study. All cases came from ophthalmology department of
      Zhejiang Province Traditional Chinese Medical Hospital, and the First People's
      Hospital of Ningbo, and Zhongshan Ophthalmic Center, Sun Yat-Sen University from
      December 2009 to October 2012. All the disease and control cases were coming from
      the same hospitals at the same period. Subjects were divided into 3 different
      groups: patients with NPDR (n = 89, 89 eyes), patients with diabetic mellitus but
      without diabetic retinopathy (NRD) (n = 96, 96 eyes) and disease-free controls (n
      = 115, 115 eyes). One eye of each subject was randomly selected for study.
      Participants aged from 40 to 70 years at baseline and all diabetic patients had a
      diabetic history of at least 5 years. Optic RNFL thickness of each subject was
      measured by spectral domain optical coherence tomography(SD-OCT). Visual function
      examinations including contrast sensitivity test in spatial frequencies of 1.5,
      3.0,6.0, 12.0, 18.0 cycles per degree (c/d), pattern electroretinograms (PERG)
      and best corrected visual acuity (BCVA) assay. The analysis of RNFL thickness in
      each group was performed at four preset locations of the optic disc (i.e.,
      temporally, superiorly, nasally, and inferiorly). To assess the structure
      function relationship, the BCVA,contrast sensitivity, PERG-P50 amplitude and
      latency to optic RNFL thickness at each quadrant were analyzed in both NPDR and
      NRD groups. RESULTS: The RNFL thickness at four preset locations of the optic
      disc (meanly, nasally, temporally, superiorly, and inferiorly) were (97.7 +/-
      13.0), (71.7 +/- 10.3), (70.9 +/- 13.3), (118.3 +/- 19.7), and (123.1 +/- 20.8)
      um in the NPDR group; (98.6 +/- 15.3), (74.8 +/- 13.1), (71.8 +/- 14.6), (119.5
      +/- 17.2), and (125.6 +/- 19.9) um in the NRD group;and (99.1 +/- 11.8), (77.4 +/
      12.6), (72.6 +/- 13.2), (119.1 +/- 18.1), and (127.1 +/- 19.3) um in the normal
      group. The nasally optic RNFL thickness was significantly different among the
      three groups (F = 8.56, P = 0.000). The thickness in the NPDR and in the NRD
      group were significantly thinner than that in the normal group (SNK-q test:q =
      3.16, 3.11, respectively; both P < 0.05). In the NPDR group, the nasally optic
      RNFL thickness was significantly thinner than that in the NRD group (SNK-q test:q
      = 3.07, P < 0.05). The inferiorly optic RNFL thickness was also significantly
      different among the three groups (F = 3.841, P = 0.035). The thickness in the
      NPDR group was significantly thinner than that in the normal group (SNK-q test:q
      = 3.090, P < 0.05). Yet, the difference of inferiorly optic RNFL thickness
      between the NRD group and the normal or the NPDR group did not reach the level of
      statistical significance (SNK-q test:q = 2.101, 1.955, P > 0.05). The temporally
      or superiorly optic RNFL thickness,or the average thickness of optic RNFL did not
      differ significantly among the three groups (F = 0.985, P = 0.375; F = 0.333, P =
      0.71; F = 0.975, P = 0.379, respectively). Contrast sensitivities (1.5, 3.0,6.0,
      12.0, 18.0 c/d), PERG-P50 amplitude and latency were all significantly correlated
      with the RNFL thickness of the nasal quadrant (nasal = 0.28, 0.26, 0.3, 0.25,
      0.45, 0.65, 0.48, respectively; P < 0.05) and the inferior quadrant (inferior =
      0.25, 0.28, 0.27, 0.26, 0.28, 0.37, 0.71; P < 0.05) in the NPDR group. Contrast
      sensitivities in high spatial frequencies (6.0, 12.0, 18.0 c/d), PERG-P50
      amplitude were also significantly correlated with the RNFL thickness of the nasal
      quadrant (nasal = 0.59, 0.45, 0.66, 0.33, respectively; P < 0.05) and the
      inferior quadrant (inferior = 0.46, 0.71, 0.52, 0.41, respectively; P < 0.05) in
      the NRD group. CONCLUSION: The optic RNFL thickness of the nasal and inferior
      quadrant have been already reduced in patients with NPRD and are significantly
      correlated with the change of vision function.

PMID- 24119965
TI  - [Effect of voltage-dependent calcium channel alpha1F subunit deficiency on the
      structure and function of the murine retina].
AB  - OBJECTIVE: To investigate the distribution and biological roles of voltage
      dependent calcium channel (VDCC) alpha1F subunit in murine retina. METHODS:
      Experimental study.alpha1F(-/-) (homozygous mutant) mice (n = 35) and
      alpha1F(+/+) (wild type) mice (n = 35) were used in this study.
      Immunohistochemistry was performed to determine the expression of VDCC alpha1F
      subunit in the mouse retina. Retinae in alpha1F(-/-) mice and age-matched control
      mice at 3, 6, 9, 14-day and 3-month after birth were paraffin embedded, sectioned
      and HE stained, and full-field electroretinogram (ERG) were also recorded at
      these time points.Statistics were based on independent samples t-test. RESULTS:
      (1) alpha1F subunit was absent in alpha1F(-/-) mice retina. But in alpha1F(+/+)
      mice retina, alpha1F subunit was expressed most strongly in the outer plexiform
      layer (OPL), less in the inner plexiform layer (IPL) and ganglion cell layer
      (GCL). (2) OPL thickness in the subunit deficient mice gradually reduced after
      birth and lost at adult age. (3) In dark-adapted ERGs,standard response showed
      that the b-wave amplitude of alpha1F(-/-) mice [(163.8 +/- 26.7) uV]
      significantly decreased compared with that of alpha1F(+/+) mice [(408.4 +/- 54.5)
      uV] (t = -9.017, P = 0.000), whereas the a-wave amplitude of alpha1F(-/-) group
      [(208.2 +/- 27.3) uV] was similar to that of control group [(196.0 +/- 24.2) uV]
      (t = 0.748, P = 0.476). CONCLUSION: This study demonstrates that the lack of VDCC
      alpha1F subunit affect the structure and function in the OPL of the murine
      retina.

PMID- 24119966
TI  - [Study on the characteristics of optic nerve meningiomas in medical
      imageology,histopathology and immunohistochemistry].
AB  - OBJECTIVE: To determine the characteristics of optic nerve meningiomas in medical
      imageology (including CT and MRI), histopathology and immunohistochemical
      expression of Vimentin, CK, S-100, EMA in tumor cells. METHODS: This was a
      retrospective study on a serial of clinical cases. Forty-eight cases were
      collected from the past 21 years at the Department of Ophthalmology, West China
      Hospital, Sichuan University. All the cases underwent surgery and were confirmed
      as optic nerve meningiomas by histopathological test, including paraffin imbedded
      sectioning and HE staining. In addition, all the cases had medical records on CT
      and 17 cases had MIR scan. Immunohistochemical staining for VIMENTIN, CK, S-100,
      EMA was performed in the 21 cases. RESULTS: Characteristics of the CT scan
      include that, in 39 cases, among them 26 cases the tumors filled in the orbit
      especially at the orbital apex, which led to the disappearance of the black
      triangle. Three cases showed enlargement and calcification of optic nerve and
      therefore train track sign was seen. Three cases showed that the masses of optic
      nerve were close to the globe and another three cases showed that the masses were
      located in the peripheral orbit. Thirteen of 17 cases MRI disclosed the big
      orbital tumors and 5 cases could better show tumor extension to optic cross or
      intracranium. Histopathological tests demonstrated meningothelial or syncytial
      type in 39 cases, transitional or mixing type in 8 cases, fiber or fibroblast
      type in 3 cases and vascular type in 2 cases. Immunohistochemistry study verified
      the positive staining rate of VIMENTIN as 90.5%(21 cases), EMA 66.7%(15 cases),
      CK 42.8%(9 cases) and S-100 23.8%(5 cases), respectively. CONCLUSIONS:
      Characteristics of CT and MRI include enlargement and tumor-like expansion of
      optic nerve. Most of the tumors reach to orbital apex and show uneven density.
      Calcification may occur in the tumor. The main pathological type of the tumors is
      meningothelial. Positive immunohistochemiscal staining for VIMENTIN and EMA may
      be helpful in diagnosis.

PMID- 24119967
TI  - [The clinical analysis of cranio-orbital communicating tumors].
AB  - OBJECTIVE: To investigate the clinical manifestations, imageological features,
      surgical approaches and prognosis of cranio-orbital communicating tumors.
      METHODS: The retrospective analysis was performed in the 22 patients of cranio
      orbital communicating tumors in the past three years. CT and MRI examinations
      were applied in all cases. Of 16 patients were treated by surgical approaches, Of
      6 patients were for radiation therapy. RESULTS: Of 22 cases, 2 cases were osteoid
      osteoma, 3 cases were meningioma, 1 case was aneurysmal bone cyst, 2 cases were
      mucous cyst, 2 cases were schwannoma, 2 cases were adenoid cystic carcinoma of
      lacrimal gland, 2 cases were metastatic carcinoma, and 2 cases were
      rhabdomyosarcoma. Other 6 cases were treated by radiotherapy without pathological
      diagnosis. 8 cases for orbital operation including excision of orbital contents
      1/8, anterior orbitotomy 3/8, and lateral orbitotomy 4/8, and 8 cases for
      transcranial operation including frontotemporal orbital roof approach 3/8 and
      pterion approach 5/8. After operation, the vision acuity of 3 cases was improved,
      of 10 cases was unchanged and of 3 cases was decreased. Two patients died of
      metastasis. Among 8 cases of transcranial operation, the complaints such as eye
      movement disorder, proptosis and conjunctival edema emerged in 1 case. However,
      among 8 cases of orbital operation, such above complaints were respectively found
      in 7, 5 and 6 cases. CONCLUSIONS: CT and MRI have the great value for diagnosis
      of cranio-orbital communicating tumors, especially combined with enhanced
      contrast MRI. Resection of cranio-orbital communicating tumors via the
      transcranial surgical approach is the effective surgical approach for cranio
      orbital communicating tumors.

PMID- 24119968
TI  - [The key parameters of design research and analysis of the Chinese reading visual
      acuity chart].
AB  - OBJECTIVE: Reading is a visual function human being used to understand
      environmental events based on writing materials. This study investigated the
      feasibility of reading visual acuity chart in assessment of reading ability by
      analysis of the key factors involved in the design of the visual acuity chart.
      METHODS: The reading level was determined as grade 3 primary school with Song as
      the font and 30 characters included in the sentences. Each of the sentences
      consisted of 27 commonly-used Chinese characters (9 characters between any two
      punctuations) and 3 punctuations. There were no contextual clues between the 80
      sentences selected. The characters had 13 different sizes with an increment of
      0.1 log unit (e.g.1.2589) and 2.5 pt was determined as the critical threshold.
      Readable test for visual target was followed as (1) 29 candidates with a raw or
      corrected visual acuity (VA)of at least 1.0 were selected to read 80 selected
      sentences with the size of characters of 2.5 pt at a distance of 40 cm, (2) the
      time used for reading with the number of characters wrongly read was recorded,
      (3) 39 sentences were selected as visual targets based on reading speed,
      effective reading position and total number of character strokes, (4) The 39
      selected sentences were then randomly divided into 3 groups with no significant
      difference among the groups in the 3 factors listed at (3) with paired t-test.
      RESULTS: This reading visual chart was at level of Grade 3 primary school with a
      total stroke number of 165-210(Mean 185 +/- 10), 13 font sizes a 0.1 log unit
      increment, a song pattern and 2.5 pt as the critical threshold. All candidates
      achieved 100% correct in reading test under 2.5 pt with an effective reading
      speed as 120.65-162 wpm (Mean 142.93 +/- 11.80) and effective reading position as
      36.03-61.48(Mean 48.85 +/- 6.81). The reading test for the 3 groups of sentences
      showed effective reading speed as (142.49 +/- 12.14) wpm,(142.86 +/- 12.55) wpm
      and (143.44 +/- 11.63) wpm respectively(t1-2 = -0.899, t2-3 = -1.295, t1-3 = 
      1.435). The reading position was 48.55 +/- 6.69, 48.99 +/- 7.49 and 49.00 +/-
      6.76, respectively(t1-2 = -1.019, t2-3 = -0.019, t1-3 = -0.816). The total number
      of character strokes was 185.54 +/- 7.55, 187.69 +/- 13.76 and 182.62 +/- 8.17,
      respectively(t1-2 = 0.191, t2-3 = 1.385, t1-3 = 1.686). CONCLUSIONS: A practical
      design of the Chinese reading visual chart should consider size, increment,
      legibility in selection of reading sentences. Reading visual acuity, critical
      threshold and effective reading speed could be used to express the reading visual
      function.

PMID- 24119969
TI  - [Visual function of seven children with malignant osteopetrosis after
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To detect long-term ocular alteration of children with malignant
      osteopetrosis after hematopoietic stem cell transplantation. METHODS: Children
      diagnosed as osteopetrosis from 5 months to 31 months underwent hematopoietic
      stem cell transplantation. Computed tomography of optic canal, FVEP, ERG and
      fundus examination were applied to assess the visual function. RESULTS: Bone
      marrow transplantation was successful. Peripheral blood test, splenohepatomegalia
      and osteosclerosis improved gradually. The mean optic canal diameters of right
      eyes before transplantation was (1.7 +/- 0.4)mm. The mean optic canal diameters
      of right eyes was (3.2 +/- 0.7)mm after transplantation. The mean optic canal
      diameters of left eyes before transplantation was (1.9 +/- 0.5)mm . The mean
      optic canal diameters of left eyes was (3.1 +/- 0.8)mm after transplantation. The
      difference between above two groups was statistically significant(t = -5.204, 
      4.211;P < 0.05). P2 latency period of FVEP prolonged in 7 cases before
      transplantation. Mean P2 latency period of FVEP decreased 21.13 ms in 5 cases
      after transplantation. Mean P2 latency period of FVEP prolonged 22.25 ms in 2
      cases after transplantation. Under light adaptation and dark adaptation, ERG
      amplitude depressed obviously in 2 cases. Two cases with optic nerve atrophy did
      not change after transplantation. CONCLUSIONS: Hematopoietic stem cell
      transplantation is an effective way to deal with malignant osteopetrosis.
      Successful transplantation has been shown to arrest visual deterioration in some
      cases.

PMID- 24119970
TI  - [Clinical observation of lymphangiectasis in conjunctivochalasis cases].
AB  - OBJECTIVE: To investigate the relationship between the occurrence and development
      of conjunctivochalasis and bulbar conjunctival lymphangiectasia. METHODS: Case
      control study. One hundred cases with conjunctivochalasis treated from January to
      March 2012 were selected to study, and 100 cases with no conjunctivochalasis as
      the control group at the same time. To observe bulbar conjunctiva lymphatic duct
      dilatation using slit lamp microscope, analysis bulbar conjunctiva and fascia
      images by OCT scanning, and ablate lymphatic of conjunctival tissue for
      pathologic examine. RESULTS: Twenty-nine eyes of the bulbar conjunctiva
      lymphangiectasia associated with 100 cases (183 eyes) conjunctivochalasis
      patients, accounting for 15.84%; 8 eyes of the ball conjunctival lymphatic
      dilation in control group of 100 cases ( 200 eyes), accounting for 4.00%. The
      difference between the two groups was statistically significant (chi(2) = 15.36,
      P < 0.001). OCT scanning showed that lymphangiectasia of the conjunctiva is at
      the subcutaneous mainly, some in the conjunctival lamina propria. They are border
      clear, full-filled fluid, single-lumen or multi lumens, not involving the fascia.
      The histopathological examination showed that the lamina propria of the bulbar
      conjunctiva mildly chronic inflammatory changes accompanied by a large number of
      lymphangiectasia. CONCLUSION: Bulbar conjunctival lymphangiectasia may be one of
      the reasons for the conjunctivochalasis.

PMID- 24119971
TI  - [Identification and early diagnosis of choroideremia and gyrate atrophy].
AB  - Choroideremia and gyrate atrophy are two kinds of heritage primary retino
      choroidal atrophy diseases. At advanced stage, their typical fundus lesions are
      conductive to identification. However, early diagnosis and intervention, which
      lead to improved prognosis and genetic benefits, are hindered by some similar
      clinical manifestation and optical examine results. Therefore, it is meaningful
      for ophthalmologists to have a comprehensive understand of these two diseases,
      and provide early diagnosis and proper intervention including genetic
      consultation.

PMID- 24119972
TI  - [The advances of epigenetic research in eye].
AB  - Epigenetics is the emergence of a new branch of genetics. Epigenetic factors
      regulate gene function and phenotype by the modulation of DNA methylation,
      histone modification, non-coding RNA expression instead of changing the DNA
      sequence; more importantly, the regulation occurs under the influence of
      environment and diet and can be passed on to the next generation. Epigenetics is
      involved in life development, maintenance of normal physiological functions of
      the human body and the pathology of many complex phenomena,such as inflammation,
      aging, tumorgenesis, etc. There is no doubt that the pathogenesis of complex eye
      diseases such as recurrence of herpes simplex keratitis, glaucoma, uveitis and
      AMD may be associated with aberrant epigenetic regulations. Therefore effect in
      vigorously carrying eye research on epigenetics may provide new insight of the
      pathogenesis of those eye diseases and development of novel treatment options.

PMID- 24119973
TI  - [New advances of femtosecond laser in cataract surgery].
AB  - Since the use of femtosecond laser (FSL) in refractive surgery, it has been
      expanded to other corneal surgeries and most recently has been applied to
      cataract surgery. The FSL can create clear corneal incisions and limbus relaxing
      incisions in any space of different shapes, at a desired depth. This has started
      the application of the technology in the lens: after a clear image is taken of
      the lens through a previously dilated pupil, circular capsulotomy is done, with
      precision in shape and diameter, and then photofragmentation of the nucleus is
      done, without the risk of damaging the posterior capsule, because it is well
      visualized, to achieve the aspiration of the nuclear material in lower even
      without applying phaco energy. In summary, FSL is now used at the level of the
      lens, with the potentiality for very precise circular and adjustable diameter
      capsulotomies, and the fragmentation of the nuclear material, allowing the less
      use of forcep and phaco machine.

PMID- 24119974
TI  - Microbiological, pathological and histological findings in four Danish pig herds
      affected by a new neonatal diarrhoea syndrome.
AB  - BACKGROUND: Neonatal diarrhoea is a frequent clinical condition in commercial
      swine herds, previously regarded to be uncomplicated to treat. However, since
      2008 it seems that a new neonatal diarrhoeic syndrome unresponsive to antibiotics
      and common management practices has emerged. Routine laboratory examinations have
      not detected any pathogen related to this syndrome. The primary purpose of this
      study was to evaluate if well-known enteric pathogens could be associated with
      outbreaks of neonatal diarrhoea, thus question the hypotheses of a new syndrome.
      Furthermore, we wanted to evaluate macroscopic and microscopic findings
      associated with these outbreaks and if possible propose a preliminary piglet
      level case-definition on syndrome New Neonatal Porcine Diarrhoea syndrome
      (NNPDS). RESULTS: Four well-managed herds experiencing neonatal diarrhoea with no
      previously established laboratory conclusion and suspected to suffer from New
      Neonatal Porcine Diarrhoea Syndrome, were selected. Within these herds, 51
      diarrhoeic and 50 non-diarrhoeic piglets at the age of three to seven days were
      necropsied and subjected to histological and microbiological examination. Faeces
      were non-haemorrhagic. Neither enterotoxigenic E. coli, Clostridium perfringens
      type A or C, Clostridium difficile, rotavirus, coronavirus, Cryptosporidium spp,
      Giardia spp, Cystoisospora suis nor Strongyloides ransomi were associated with
      diarrhoea in the investigated outbreaks. Macroscopically, the diarrhoeic piglets
      were characterized by filled stomachs and flaccid intestines without mucosal
      changes. The predominant histological lesions were villous atrophy in jejunum and
      ileum. Epithelial lesions in colon were seen in one third of the case piglets.
      CONCLUSIONS: The results of the study supported the hypothesis that a new
      neonatal porcine diarrhoea was present in the investigated herds, since no known
      pathogen(s) or management factors could explain the diarrhoeal outbreaks. Based
      on the findings in the four herds the following case-definition of NNPDS was
      suggested: Non-haemorrhagic diarrhoea during the first week of life, without
      detection of known infectious pathogens, characterized by milk-filled stomachs
      and flaccid intestines at necropsy.

PMID- 24119975
TI  - Usability and perceived usefulness of Personal Health Records for preventive
      health care: a case study focusing on patients' and primary care providers'
      perspectives.
AB  - Personal Health Records (PHR) are electronic applications for individuals to
      access, manage and share their health information in a secure environment. The
      goal of this study was to evaluate the usefulness and usability of a Web-based
      PHR technology aimed at improving preventive care, from both the patients' and
      primary care providers' perspectives. We conducted a multi-method descriptive
      study that included direct observations, concurrent think-aloud, surveys,
      interviews and focus groups in a suburban primary care clinic. Patients found the
      tailored health recommendations useful and the PHR easy to understand and use.
      They also reported asking useful health-related questions to their physicians
      because of using the system. Generally, care providers were interested in using
      the system due to its useful content and impact on patient activation. Future
      successful systems should be better integrated with hospital records; put more
      emphasis on system security; and offer more tailored health information based on
      comprehensive health databases. 

PMID- 24119976
TI  - Temporal artery biopsy--how can we improve performance?
AB  - INTRODUCTION: Temporal arteritis is a rare systemic disease of undefined
      aetiology. The British Society for Rheumatology has issued evidence-based
      guidance in the form of an investigative algorithm, central to which is biopsy of
      the superficial temporal artery (TA). Currently in Glasgow these patients are
      being referred to the regional vascular unit. We sought to identify areas where
      local practice could be improved. METHODS: This was a retrospective review of TA
      biopsy performed since the amalgamation of vascular services in Glasgow. RESULTS:
      There were 32 cases with a complete dataset. The majority of patients referred
      were women (66%), with a mean age of 68 years (range 43-86 years). A variety of
      different clinical symptoms were reported. The mean ESR was 53 (range 2-122). The
      median waiting time from referral to surgical biopsy was 6 days (inter-quartile
      range 2-8 days). Seven patients waited for more than 14 days for the procedure to
      be performed. There were four positive biopsies in this case series. TA biopsy
      influenced the duration of glucocorticosteroid therapy. CONCLUSION: From this
      study we believe that the following changes to local practice would be simple,
      cost effective and could improve the quality of patient care delivered.

PMID- 24119977
TI  - Comparison of above- and below-elbow casting for pediatric distal metaphyseal
      forearm fractures.

PMID- 24119978
TI  - A band-like balding disorder.

PMID- 24119979
TI  - Vitamin D supplementation: bones of contention.

PMID- 24119980
TI  - Effects of vitamin D supplements on bone mineral density: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Findings from recent meta-analyses of vitamin D supplementation
      without co-administration of calcium have not shown fracture prevention, possibly
      because of insufficient power or inappropriate doses, or because the intervention
      was not targeted to deficient populations. Despite these data, almost half of
      older adults (older than 50 years) continue to use these supplements. Bone
      mineral density can be used to detect biologically significant effects in much
      smaller cohorts. We investigated whether vitamin D supplementation affects bone
      mineral density. METHODS: We searched Web of Science, Embase, and the Cochrane
      Database, from inception to July 8, 2012, for trials assessing the effects of
      vitamin D (D3 or D2, but not vitamin D metabolites) on bone mineral density. We
      included all randomised trials comparing interventions that differed only in
      vitamin D content, and which included adults (average age >20 years) without
      other metabolic bone diseases. We pooled data with a random effects meta-analysis
      with weighted mean differences and 95% CIs reported. To assess heterogeneity in
      results of individual studies, we used Cochran's Q statistic and the I(2)
      statistic. The primary endpoint was the percentage change in bone mineral density
      from baseline. FINDINGS: Of 3930 citations identified by the search strategy, 23
      studies (mean duration 23.5 months, comprising 4082 participants, 92% women,
      average age 59 years) met the inclusion criteria. 19 studies had mainly white
      populations. Mean baseline serum 25-hydroxyvitamin D concentration was less than
      50 nmol/L in eight studies (n=1791). In ten studies (n=2294), individuals were
      given vitamin D doses less than 800 IU per day. Bone mineral density was measured
      at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total
      body, or forearm) in each study, so 70 tests of statistical significance were
      done across the studies. There were six findings of significant benefit, two of
      significant detriment, and the rest were non-significant. Only one study showed
      benefit at more than one site. Results of our meta-analysis showed a small
      benefit at the femoral neck (weighted mean difference 0.8%, 95% CI 0.2-1.4) with
      heterogeneity among trials (I(2)=67%, p<0.00027). No effect at any other site was
      reported, including the total hip. We recorded a bias toward positive results at
      the femoral neck and total hip. INTERPRETATION: Continuing widespread use of
      vitamin D for osteoporosis prevention in community-dwelling adults without
      specific risk factors for vitamin D deficiency seems to be inappropriate.
      FUNDING: Health Research Council of New Zealand.

PMID- 24119981
TI  - Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors.
AB  - Acute atherosis (Aa) affects uteroplacental spiral arteries in 20-40% of cases of
      preeclampsia. Its hallmark is lipid-filled, CD68-positive foam cells. It usually
      develops in the decidua (the pregnancy endometrium) at the distal ends of
      arteries that are often unremodelled in their proximal segments. Aa resembles the
      early stages of atherosclerosis, which becomes symptomatic in the middle-aged and
      elderly, in contrast to the young age of pregnant women with Aa. Although the
      mechanisms of Aa are largely unknown, they are likely to resemble those of early
      atherosclerosis, which is an inflammatory lesion of the arterial wall. However,
      Aa is likely to have added pregnancy-specific features. Because it also occurs in
      normotensive pregnancies, complicated by foetal growth restriction, diabetes
      mellitus or autoimmune disease or even without any complications, we suggest that
      Aa is the final manifestation of several inflammatory processes. We revisit an
      old proposition that immunological incompatibility between mother and foetus may
      sometimes induce Aa. We propose that excessive inflammatory activation, of other
      aetiologies, primarily in the decidua basalis, may explain the different ways in
      which Aa occurs. We speculate that the subset of women who develop these lesions
      may be at an increased risk of atherosclerotic arterial disease later in life. We
      hypothesise that use of anti-atherogenic statins during established preeclampsia
      may ameliorate Aa, improve uteroplacental perfusion and enhance pregnancy
      outcome. 

PMID- 24119982
TI  - A single-center experience with the ross procedure over 20 years.
AB  - BACKGROUND: The Ross procedure offers several potential advantages in a young
      patient population. The widespread use of the procedure is still limited due to
      the technical challenge. Pulmonary homograft stenosis and autograft dilatation
      remain a matter of concern. We present the long-term outcome in a single center
      with special emphasis on mortality and need for valvular reintervention. METHODS:
      All patients who received a Ross procedure as freestanding root replacement
      (modified Yacoub technique) at our institution between 1991 and 2011 were
      followed. Descriptive statistical methods and Kaplan-Meier analyses were
      performed. RESULTS: A total of 246 patients (191 males, 55 females) underwent the
      Ross procedure during the study period. There were 176 adults and 70 pediatric
      patients with an average age of 36 +/- 10 and 10 +/- 5 years, respectively. The
      median follow-up was 10 years. Twelve (4.9%) subjects were lost to follow-up.
      Early mortality was 1.6%. Overall mortality was comparable with an age and sex
      matched population for adult patients. The linearized risk for reoperation per
      patient-year was 0.6% for the autograft and 0.6% for the right ventricular
      outflow tract, with a mean time to surgery of 6.4 +/- 4.9 years. Overall freedom
      from reintervention was 95% at 5 years, 88% at 10 years, and 81% at 15 years.
      CONCLUSIONS: The Ross procedure provides good early results and an excellent long
      term survival. It represents an excellent method of aortic valve replacement in
      children and young adults. Root reinforcement techniques and aortic reduction
      plasty may be beneficial, especially in adult patients with native aortic valve
      regurgitation.

PMID- 24119983
TI  - Effect of hemostatic material on sternal healing after cardiac surgery.
AB  - BACKGROUND: Postoperative sternal infection and dehiscence cause increased
      morbidity, mortality, and socioeconomic costs as well as patient discomfort and
      pain. Some predisposing factors have been uncovered but others remain
      uninvestigated. Among these are the influence of topical hemostatic agents such
      as bone wax (BW) and Ostene (Ceremed Inc, Los Angeles, CA) a new, water-soluble
      polymer wax (WSW). The object of this study was to investigate the impact of
      topical hemostatic agents on sternal healing in patients. METHODS: In total, 50
      patients subjected to elective cardiac surgery and requiring intraoperative
      hemostatic treatment were randomized to 1 of 2 treatment groups: BW or WSW.
      Twenty-five patients without need for sternal hemostasis constituted a control
      group. The doctors analyzing the endpoints were blinded to the treatment.
      Radiologic bone healing was assessed by a radiologist using computed tomography
      at 3 and 6 months postoperatively. Quality of life and bodily pain was assessed
      by questionnaires (Short Form-36 and Visual Analogue Scale). RESULTS: No patients
      displayed complete radiologic healing at 3 months. Bone healing (evaluated semi
      quantitatively at a score from 0 to 10) was significantly impaired in the BW
      group compared with both the control and WSW groups at both 3 and 6 months
      postoperatively (p < 0.0001). Radiologic bone healing was positively correlated
      with physical functioning score (Short Form-36) (p < 0.001). Pain scores were
      generally low (<1) at both 3 and 6 months with no significant difference between
      study groups. CONCLUSIONS: The results from this study suggest that WSW provides
      a useful alternative to BW when topic hemostasis on the sternum is required.

PMID- 24119984
TI  - Optimal timing of thoracoscopic drainage and decortication for empyema.
AB  - BACKGROUND: Although video-assisted thoracic surgery (VATS) pleural drainage and
      decortication have been proven to be effective treatments in the early stages of
      empyema, the optimal timing of VATS is still not clear. To assess the
      effectiveness of early VATS drainage and decortication, we reviewed the records
      of patients who underwent VATS and open decortication for empyema. METHODS: One
      hundred twenty-eight patients with empyema were treated with VATS and open
      decortication over 8 years at Korea University Anam Hospital. The VATS patients
      (120 patients) were divided into 3 groups based on the interval between the onset
      of chest symptoms and the time of operation (group 1: <2 weeks; group 2: 2 to 4
      weeks; group 3: >4 weeks). Additional 8 open decortication patients with symptom
      durations greater than 4 weeks were compared with group 3 patients. RESULTS:
      Groups 1 and 2 showed shorter chest tube duration, postoperative hospital stay,
      surgical procedure time, and fewer prolonged air leaks than group 3. No
      significant difference was noted between groups 1 and 2; and no difference was
      noted in the length of postoperative intensive care unit stays or the
      reintervention and reoperation rates among the 3 groups. In chronic empyema
      patients, group 3 showed shorter chest tube duration than the open decortication
      group. CONCLUSIONS: Patients with symptom durations of less than 4 weeks showed
      better early results than those with symptom durations greater than 4 weeks.
      Thus, symptom duration can be considered a reliable preoperative factor in
      deciding the surgical management of empyema or cases involving loculated pleural
      effusion.

PMID- 24119986
TI  - Effects of prophylactic use of sirolimus on bronchiolitis obliterans syndrome
      development in lung transplant recipients.
AB  - BACKGROUND: Sirolimus (SIR) has been shown to stabilize the lung function in lung
      transplant recipients with bronchiolitis obliterans syndrome (BOS). However,
      there is no long-term data on the prophylactic use of SIR in lung transplant
      recipients. This retrospective study examines the effects of SIR in the
      prevention of BOS. METHODS: From 1999 to 2009, 24 lung transplant recipients
      whose maintenance immunosuppression regimen consisted of tacrolimus (Tac),
      mycophenolate mofetil (MMF) or azathioprine (AZA), and prednisone (Pred), were
      switched to Tac, SIR, and Pred at 1 year after transplantation. From these 24
      patients, 5 developed side effects that necessitated the cessation of SIR within
      1 year, while 19 patients tolerated long-term use of SIR. The clinical outcomes
      of these 19 patients (SIR group) were compared with 22 lung transplant recipients
      whose immunosuppression regimen consisted of Tac, MMF or AZA, and Pred from the
      time of transplant (MMF group). Survival rates and freedom from BOS were
      calculated by the Kaplan-Meier method. RESULTS: The SIR group had a lower
      incidence of BOS and viral infection (p = 0.05), and higher survival rates (p =
      0.004). The SIR group had lower levels of Tac and received less Pred. The
      incidences of acute rejection, carcinoma, hypertension, and diabetes were similar
      between both groups. CONCLUSIONS: Results from this study suggest that conversion
      to SIR 1 year after lung transplantation improves survival and decreases the
      development of BOS. Randomized studies with higher number of patients are needed
      to determine the prophylactic efficacy of sirolimus in preventing the development
      of BOS.

PMID- 24119985
TI  - Impact of perioperative acute kidney injury as a severity index for thirty-day
      readmission after cardiac surgery.
AB  - BACKGROUND: Of patients undergoing cardiac surgery in the United States, 15% to
      20% are re-hospitalized within 30 days. Current models to predict readmission
      have not evaluated the association between severity of postoperative acute kidney
      injury (AKI) and 30-day readmissions. METHODS: We collected data from 2,209
      consecutive patients who underwent either coronary artery bypass or valve surgery
      at 7 member hospitals of the Northern New England Cardiovascular Disease Study
      Group Cardiac Surgery Registry between July 2008 and December 2010.
      Administrative data at each hospital were searched to identify all patients
      readmitted to the index hospital within 30 days of discharge. We defined AKI
      stages by the AKI Network definition of 0.3 or 50% increase (stage 1), twofold
      increase (stage 2), and a threefold or 0.5 increase if the baseline serum
      creatinine was at least 4.0 (mg/dL) or new dialysis (stage 3). We evaluate the
      association between stages of AKI and 30-day readmission using multivariate
      logistic regression. RESULTS: There were 260 patients readmitted within 30 days
      (12.1%). The median time to readmission was 9 (interquartile range, 4 to 16)
      days. Patients not developing AKI after cardiac surgery had a 30-day readmission
      rate of 9.3% compared with patients developing AKI stage 1 (16.1%), AKI stage 2
      (21.8%), and AKI stage 3 (28.6%, p < 0.001). Adjusted odds ratios for AKI stage 1
      (1.81; 1.35, 2.44), stage 2 (2.39; 1.38, 4.14), and stage 3 (3.47; 1.85 to 6.50).
      Models to predict readmission were significantly improved with the addition of
      AKI stage (c-statistic 0.65, p = 0.001) and net reclassification rate of 14.6%
      (95% confidence interval: 5.05% to 24.14%, p = 0.003). CONCLUSIONS: In addition
      to more traditional patient characteristics, the severity of postoperative AKI
      should be used when assessing a patient's risk for readmission.

PMID- 24119987
TI  - Early left ventricular abnormality/dysfunction in obese children affected by
      NAFLD.
AB  - BACKGROUND AND AIMS: Although it is generally accepted that non alcoholic fatty
      liver disease (NAFLD) is linked to increased risk of cardiovascular disease, the
      presence of abnormalities in cardiac function among NAFLD children is limited and
      controversial. Aim of the study was to detect cardiac abnormalities/dysfunction
      in a paediatric population of NAFLD. METHODS AND RESULTS: Anthropometric,
      laboratory, cardiovascular fitness, 24 h blood pressure monitoring and Doppler
      echocardiography parameters were obtained in 50 untreated children (37 males;
      mean age 12.2 + 2.5) with biopsy-proven NAFLD. Abnormalities in both cardiac
      function and geometry could be identified in the whole study population:
      prevalence of about 35% in left ventricular hypertrophy, 14% of concentric
      remodelling and 16% of left atrial dilatation. Furthermore children with NAFLD
      (NAS score <5) showed lower cardiac alterations compared to NASH patients (NAS
      score >5). After adjusting for age, sex and BMI, a positive correlation was found
      only between LV mass and NAS score (p < 0.001). CONCLUSION: Our results suggest
      that cardiac dysfunction can be detectable early in NAFLD children and this is
      not linked to cardiovascular and metabolic alteration, other than to liver
      damage. Although as a preliminary stage, we can speculate a possible direct
      relationship between liver and heart steatosis, already occurring during
      childhood.

PMID- 24119988
TI  - Is high-intensity exercise better than moderate-intensity exercise for weight
      loss?
AB  - This viewpoint debates the state-of-the-art research focusing on the optimal
      intensity of the exercise programs for inducing a sustained weight or fat-mass
      loss in overweight/obese people. In our demanding society, the most attractive
      messages in the popular press are those promising the best results in a short
      time. This might explain the emphasis given by media to those scientific articles
      that report the efficacy on weight loss of exercise programs by their shorter
      duration and higher intensity. However, in the literature on overweight or obese
      people, there is little conclusive evidence for more favorable effects with high
      intensity training than with continuous moderate-intensity exercise on body
      weight or fat mass loss. Since both exercise protocols have been demonstrated as
      useful to reduce body weight, the decision on the intensity of exercise
      prescription should be individualized and based on outcomes different from fat or
      weight loss. In this regard, there are pro and contra arguments for the
      prescription of high-intensity aerobic exercise in obese people. Among the pro
      arguments, is the demonstration that, in several studies, high-intensity training
      appears to induce superior improvements in aerobic fitness. Among the contra
      arguments to prescribe high-intensity exercise is the demonstration that
      prescribing a higher-intensity exercise decreases adherence and results in the
      completion of less exercise. Thus, a successful exercise program should be
      proposed at a moderate intensity and a low perceived effort because obese
      subjects who have low self-efficacy, poor mood status, and are not familiar with
      high-intensity workouts could easily drop out. 

PMID- 24119989
TI  - Postprandial effects of potassium supplementation on vascular function and blood
      pressure: a randomised cross-over study.
AB  - BACKGROUND AND AIMS: Endothelial dysfunction, as assessed by flow mediated
      dilatation (FMD) is an early event in atherosclerosis and an independent
      predictor of cardiovascular events. The effect of potassium supplementation on
      endothelial function and blood pressure (BP) in the postprandial state is not
      known. The aim of this study was to assess endothelial function using FMD in
      healthy volunteers. METHODS AND RESULTS: Thirty-two normotensive volunteers
      received a meal with 36 mmol potassium (High K) and a control 6 mmol potassium
      (Low K) meal on 2 separate occasions in a randomized order. FMD and BP were
      measured while participants were fasting and at 30, 60, 90 and 120 min after the
      meal. There was a postprandial decrease in FMD in both groups. FMD decreased
      overall less after the High K meal compared to the Low K meal (meal effect p <
      0.05). Both meals produced a postprandial decrease in BP at 30 min which returned
      to baseline levels by 120 min. No significant differences in BP were observed
      between meals. FMD and systolic BP were negatively correlated at 90 (r = -0.54
      0.55, p < 0.01) and 120 min (r = -0.42-0.56, p < 0.01) after both meals.
      CONCLUSIONS: A high potassium meal, which contains a similar amount of potassium
      as 2.5 serves of bananas, can lessen the postprandial reduction in brachial
      artery FMD when compared to a low potassium meal.

PMID- 24119990
TI  - Comparisons of spot vs 24-h urine samples for estimating population salt intake:
      validation study in two independent samples of adults in Britain and Italy.
AB  - OBJECTIVES: To assess the reliability and reproducibility of estimations of group
      mean 24-h urinary sodium (Na) excretion through timed spot urines compared to 24
      h urinary Na output in two independent cross-sectional population samples
      including men and women and different ethnic groups. METHODS AND RESULTS: Study 1
      was carried out in Britain and included 915 untreated 40-59 yrs male and female
      participants (297 white, 326 of black African origin and 292 South Asian). Study
      2 was carried out in Italy and included 148 white men (mean age 58.3 yrs). All
      participants provided both a 24-h urine collection and a timed urine sample as
      part of population surveys. Na, creatinine (Cr) and volume (V) were measured in
      all samples. Age, body mass index (BMI) and blood pressure (BP) were also
      measured. We compared the daily Na excretion through 24-h urine (gold standard)
      with its estimate from timed urine samples with two methods: Tanaka's predictions
      and Arithmetic extrapolations, and assessed them with correlation coefficients,
      Bland-Altman plot, prediction of quintile position and Receiver Operating
      Characteristic (ROC) Areas Under the Curve (AUC) for a cut-off of <100 mmol of
      Na/day. In Study 1 (discovery study) with the Tanaka method there were poor
      correlations between predicted and measured 24-h Na excretions in different
      ethnic groups and genders (r Spearman from 0.055 [R(2) = 0.003] in black women to
      0.330 [R(2) = 0.11] in white women). The Bland-Altman plots indicated consistent
      bias with overestimate for low and underestimate for high intakes. ROC AUCs
      varied from 0.521 to 0.652 with good sensitivity (95-100%) but very poor
      specificity (0-9%). With the Arithmetic extrapolations correlations varied from
      0.116 [R(2) = 0.01] to 0.367 [R(2) = 0.13]. Bias was detected with both Bland
      Altman plots and through quintile analyses (underestimate at low levels and
      overestimate at high levels). Finally, ROC AUCs varied from 0.514 to 0.640 with
      moderate sensitivity (64-70%) but low specificity (20-53%). In Study 2
      (validation study) results were consistent with the discovery phase in white men.
      CONCLUSION: Based on these results, 24-h urinary collection for the measurement
      of Na excretion remains the preferred tool for assessing salt intake when
      compared with reported methods based on timed spot urine samples.

PMID- 24119991
TI  - Comment on: "Early insulin treatment in type 2 diabetes: ORIGINal sin or valuable
      choice as ORIGINal treatment? An open debate on the ORIGIN study results".

PMID- 24119992
TI  - We're not ready to encourage children to be "lean" rather than "fit".

PMID- 24119993
TI  - Body mass index, cardiac surgery and clinical outcome. A single-center experience
      with 9125 patients.
AB  - BACKGROUND AND AIM: There is evidence for a J-shaped association between Body
      Mass Index (BMI) and all-cause mortality in general populations. In cardiac
      surgical patients, the effect of BMI on mortality and major adverse cardiac and
      cerebrovascular events (MACCE) is not completely clear. METHODS AND RESULTS: We
      investigated the effect of BMI on MACCE (primary endpoint), as well as intensive
      care unit (ICU)-related outcomes and mid-term mortality in 9125 consecutive
      patients who were operated on at our institution between July 2009 and July 2012.
      Of the study cohort, 3.0% were underweight (BMI < 20 kg/m(2)), 28.0% had a normal
      BMI (20-24.99 kg/m(2)), 43.1% were overweight (BMI 25-29.99 kg/m(2)), 19.3% were
      obese (BMI 30-34.99 kg/m(2)), and 6.6% were severely obese (BMI >= 35 kg/m(2)).
      Compared with overweight patients (lowest incidence of MACCE), the multivariable
      adjusted odds ratio of MACCE in severely obese patients was 1.39 (95% CI: 1.03
      1.87). Underweight and severely obese patients had the longest risk-adjusted
      duration of mechanical ventilator support and ICU stay (P-values 0.004-0.001).
      The red blood cell concentrates requirement was highest in underweight patients
      (P < 0.001). Compared with normal and overweight patients, the multivariable
      adjusted hazard ratio of 2-year mortality was higher in underweight patients
      (1.72 [95% CI: 1.26-2.36] and =2.07 [95% CI: 1.51-2.83], respectively), but did
      not differ significantly in severely obese patients. CONCLUSION: Data demonstrate
      that both severe obesity and underweight are independent risk factors for
      operative complications in cardiac surgical patients. With respect to mid-term
      survival, special attention should be paid to underweight patients scheduled for
      cardiac surgery.

PMID- 24119994
TI  - Entomological determinants of insecticide-treated bed net effectiveness in
      Western Myanmar.
AB  - BACKGROUND: In a large cluster randomized control trial of insecticide-treated
      bed nets (ITN) in Western Myanmar the malaria protective effect of ITN was found
      to be highly variable and, in aggregate, the effect was not statistically
      significant. A coincident entomological investigation measured malaria vector
      abundance and biting behaviour and the human population sleeping habits, factors
      relevant to ITN effectiveness. METHODS: Entomological surveys were carried out
      using different catching methods to identify potential malaria vector species and
      characterise their biting habits. The salivary glands were dissected from all
      female anophelines caught to identify sporozoites by microscopy. FINDINGS:
      Between 1995 and 2000 a total of 4,824 female anopheline mosquitoes were caught
      with various catching methods. A total of 916 person nights yielded 3,009 female
      anopheline mosquitoes between 6 pm and 6 am. Except for Anopheles annularis,
      which showed no apparent preference (51% outdoor biting), all major species
      showed a strong preference for outdoor biting; Anopheles epiroticus (79%),
      Anopheles subpictus (72%), Anopheles maculatus (92%), Anopheles aconitus (85%)
      and Anopheles vagus (72%). Most human biting occurred in the early evening with
      the peak biting time between 6 pm and 7 pm (35%). Overall 51% (1447/2837) of all
      bites recorded were between 6 pm and 8 pm. A large proportion of children were
      not sleeping under an ITN during peak biting times. Only one An. annularis
      mosquito (0.02%) had malaria sporozoites identified in the salivary glands.
      CONCLUSIONS: Peak vector biting occurred early in the evening and mainly occurred
      outdoors. The limited efficacy of ITN in this area of Western Myanmar may be
      explained by the biting behaviour of the prevalent Anopheles mosquito vectors in
      this area.

PMID- 24119995
TI  - Differences in Haemophilus parasuis adherence to and invasion of AOC-45 porcine
      aorta endothelial cells.
AB  - BACKGROUND: The pathogenesis of Haemophilus parasuis depends on the bacterium's
      ability to interact with endothelial cells and invade adjacent tissues. In this
      study, we investigated the abilities of eight H. parasuis reference strains
      belonging to serovars 1, 2, 4, 5, 7, 9, 10 and 13 to adhere to and invade porcine
      aortic endothelial cells (AOC-45 cell line). RESULTS: The strains belonging to
      serovars 1, 2 and 5 were able to attach at high rates between 60 and 240 min of
      incubation, and serovars 4, 7 and 13 had moderate attachment rates; however, the
      strains belonging to serovars 9 and 10 had low adherence at all time points.
      Strong adherence was observed by scanning electron microscopy for the strains of
      serovars 5 and 4, which had high and moderate numbers, respectively, of H.
      parasuis cells attached to AOC-45 cells after 240 min of incubation. The highest
      invasiveness was reached at 180 min by the serovar 4 strain, followed by the
      serovar 5 strain at 240 min. The invasion results differed substantially
      depending on the strain. CONCLUSION: The reference strains of H. parasuis
      serovars 1, 2, 4 and 5 exhibited high adhesion and invasion levels to AOC-45
      porcine aorta endothelial cells, and these findings could aid to better explain
      the pathogenesis of the disease caused by these serovars.

PMID- 24119996
TI  - Cost of major surgery in the sarcopenic patient.
AB  - BACKGROUND: Sarcopenia is associated with poor outcomes after major surgery.
      There are currently no data regarding the financial implications of providing
      care for these high-risk patients. STUDY DESIGN: We identified 1,593 patients
      within the Michigan Surgical Quality Collaborative (MSQC) who underwent elective
      major general or vascular surgery at a single institution between 2006 and 2011.
      Patient sarcopenia, determined by lean psoas area (LPA), was derived from
      preoperative CT scans using validated analytic morphomic methods. Financial data
      including hospital revenue and direct costs were acquired for each patient
      through the hospital's finance department. Financial data were adjusted for
      patient and procedural factors using multiple linear regression methods, and Mann
      Whitney U test was used for significance testing. RESULTS: After controlling for
      patient and procedural factors, decreasing LPA was independently associated with
      increasing payer costs ($6,989.17 per 1,000 mm(2) LPA, p < 0.001). The influence
      of LPA on payer costs increased to $26,988.41 per 1,000 mm(2) decrease in LPA (p
      < 0.001) in patients who experienced a postoperative complication. Further, the
      covariate-adjusted hospital margin decreased by $2,620 per 1,000 mm(2) decrease
      in LPA (p < 0.001) such that average negative margins were observed in the third
      of patients with the smallest LPA. CONCLUSIONS: Sarcopenia is associated with
      high payer costs and negative margins after major surgery. Although postoperative
      complications are universally expensive to payers and providers, sarcopenic
      patients represent a uniquely costly patient demographic. Given that sarcopenia
      may be remediable, efforts to attenuate costs associated with major surgery
      should focus on targeted preoperative interventions to optimize these high risk
      patients for surgery.

PMID- 24119997
TI  - [Replantation and delayed replantation of avulsed young permanent teeth].

PMID- 24119998
TI  - [Investigation of root and canal morphology of human primary mandibular second
      molar by cone-beam CT].
AB  - OBJECTIVE: To investigate the root and canal morphology of primary mandibular
      second molars in a Chinese population by cone-beam CT(CBCT). METHODS: A total of
      305 CBCT images of 305 children aged 4-8 years were collected, who came to West
      China Dental Hospital from October, 2011 to March, 2012 due to supernumerary
      teeth, dental trauma, orthodontic treatment or oral maxillofacial tumor. Primary
      mandibular second molars which roots were full developed, without periapical
      infection or apical root resorption were enrolled. All the images were analyzed
      by two researchers. The data were statistically analyzed by software SPSS 19.0.
      RESULTS: Four hundred and thirty-seven primary mandibular second molars(PMSM)
      showed single mesial root except one which had two. Three hundred and twenty-five
      (74.4%) teeth had one distal root, 111(25.4%) teeth had two and one had three.
      There were 424(97.0%) teeth which had two mesial canals and 13(3.0%) had one.One
      hundred and three(23.6%) teeth had one distal root with one canal, 222(50.8%) had
      one distal root with two canals, 106(24.3%) had two distal roots with two canals,
      5(1.1%) had two roots with three canals and 1(0.2%) had three roots with three
      canals. The root canal system of PMSM had ten variants in this study. The
      prevalence of three-rooted PMSM had significant differences from different
      genders (P = 0.000) and different sides (P = 0.028). CONCLUSIONS: Majority of
      primary mandibular second molars had two roots, and the minority had three roots.
      The prevalence of three-rooted molars in males were higher than that in females.
      Mesial and distal roots of primary mandibular second molars often had two canals.

PMID- 24119999
TI  - [Expression of LIM mineralization protein-1 in the apical papilla and dental pulp
      tissues of human teeth].
AB  - OBJECTIVE: To examine the expression of LIM mineralization protein-1 (LMP-1) in
      the apical papilla and dental pulp tissues of human immature permanent teeth and
      to investigate the role of LMP-1 in the development and maturation of pulp-dentin
      complex. METHODS: Forty-eight healthy premolars in need of extraction for
      orthodontic treatment were obtained with 24 immature permanent teeth and 24
      mature permanent teeth. After extraction, the apical papilla was detached from
      the dental pulp in the immature permanent tooth and the dental pulp of mature
      permanent tooth was rapidly removed. The samples were divided into 3 groups:
      group 1, apical papilla of immature permanent teeth (root formed 2/3 of its full
      length); group 2, dental pulp tissues of immature permanent teeth; group 3,
      dental pulp tissues of mature permanent teeth. There were 24 samples for each
      group.Half of them were used for reverse transcriptien-PCR (RT-PCR) detection,
      and the other half were used for Western blotting detection. Band intensities
      were quantified using Meta Morph software 6.2.6 and subsequently normalized by
      dividing the band gray value of the target gene by the intensity of its
      corresponding beta-actin. Two-sample t test was used to analyze the difference of
      expression intensity between group 1 and group 2 as well as group 2 and group 3
      with SPSS 13.0 software package.Statistical significance was established as P <
      0.05. RESULTS: As indicated by RT-PCR, LMP-1 expressed in the apical papilla,
      dental pulp of immature permanent teeth and the dental pulp of mature permanent
      teeth were 0.25 +/- 0.09, 0.46 +/- 0.24 and 0.31 +/- 0.10 respectively. The
      expression intensity of LMP-1 mRNA in the dental pulp tissues of human immature
      permanent teeth were significantly higher than that in the apical papilla
      tissues(t = 2.92) and that in the dental pulp tissues of human mature permanent
      teeth (t = 2.31) (P < 0.05). As indicated by Western blotting, LMP-1 expressed in
      the three groups were 0.33 +/- 0.08, 0.82 +/- 0.10 and 0.52 +/- 0.19
      respectively. The expression intensity of LMP-1 protein in the dental pulp
      tissues of human immature permanent teeth were significantly higher than that in
      the apical papilla tissues(t = 3.33) and that in the dental pulp tissues of human
      mature permanent teeth (t = 3.11) (P < 0.05). CONCLUSIONS: LMP-1 were positively
      expressed in all the samples including apical papilla of immature permanent
      teeth, dental pulp of immature and mature permanent teeth at the level of both
      mRNA and protein, but with different intensity. LMP-1 could play an important
      role in the development and maturation of pulp-dentin complex.

PMID- 24120000
TI  - [Isolation, culture and identification of human odontoclasts].
AB  - OBJECTIVE: To isolate, culture and identify odontoclasts in vitro and to
      establish a method of culturing human odontoclasts. METHODS: Healthy and
      retentive deciduous teeth were extracted, and then placed in alpha-minimum
      essential medium containing 0.1% collagenase and 0.2% dispase for 1
      h.Odontoclasts were obtained and incubated from the absorbing root surfaces of
      deciduous teeth.Isolated cells were viewed by inverted phase contrast microscope
      firstly. Then, the isolated odontoclasts were morphologically observed by
      hematoxylin and eosin staining (HE) and tartrate-resistant acid phosphatase
      (TRAP) staining. The prepared teeth slices were cocultured with the isolated
      odontoclasts and scanning electronic microscope(SEM) was used to demonstrate the
      presence of resorption lacunae. RESULTS: The isolated odontoclasts appeared as
      multinucleated giant cell with many vacuolus in cytoplasm. TRAP staining
      demonstrated that the cytoplasm of the odontoclasts was full of claret-red
      positive particles.Resorption lacunae on teeth slices which cocultured with
      odontoclasts were seen under SEM. CONCLUSIONS: Enzyme digestion is an effective
      method to isolate odontoclasts from absorbing root surface of deciduous teeth.

PMID- 24120001
TI  - [Comparison of bonding properties of five adhesives in primary dentin].
AB  - OBJECTIVE: To evaluate the microtensile bond strength (uTBS) of five dentin
      adhesives and their respective fracture modes. METHODS: The flat dentine surfaces
      of 75 primary teeth were randomly divided into five groups,which was treated with
      FL-BondII(group A), Clearfil Protect Bond(group B), Clearfil SE Bond(group C),
      Adper(TM) Easy One(group D), and Single Bond 2(group E) respectively. The uTBS
      was determined with microtensile tester and the fracture mode was observed by
      scanning electron microscope(SEM). RESULTS: The mean uTBS for group A,B,C,D and E
      was (28.3 +/- 2.2), (32.4 +/- 2.5), (38.3 +/- 2.8), (32.9 +/- 3.4) and (23.2 +/-
      1.9) MPa respectively. There was significant difference between group C and group
      A,E (P < 0.01), and no significant difference between group C and group B,D.
      There was no significant difference between group A and group E (P > 0.05). The
      SEM indicated that there was no significant difference in the fracture mode.
      CONCLUSIONS: The bonding property of Clearfil Protect Bond is equivalent to
      Clearfil SE Bond and Adper(TM) Easy One, superior to Single Bond 2 and more
      suitable for primary dentin bonding .

PMID- 24120002
TI  - [Effect of mineral trioxide aggregate on proliferation and differentiation of rat
      dental papilla cells].
AB  - OBJECTIVE: To investigate the effects of mineral trioxide aggregate(MTA) on the
      proliferation and differentiation of rat dental papilla cells(RDPC). METHODS:
      RDPC were cultured by tissue block method and identified.RDPC of the third
      passage were cultured with material extract fluid containing different mass
      concentrations of MTA (0.002, 0.02,0.2, 2 and 20 g/L) for 3 d, those cultured
      with routine culture fluid served as control group. The proliferation-related
      parameters were measured by methyl thiazolyl tetrazolium(MTT) assay. RDPC were
      cultured with material extract fluids containing 0.002 g/L MTA, those cultured
      with routine culture fluid served as control group, the activity of alkaline
      phosphatase(ALP) at 1, 3,5, 7 d and the level of collagen I at 1, 3,5 d were
      detected. RESULTS: MTT results showed that the A value of RDPC of group 20 g/L
      (0.092 +/- 0.011) was less than that of the control group (0.249 +/- 0.006) at 3
      d(P < 0.01), the A value of RDPC of group 0.02 g/L (0.267 +/- 0.005) and 0.002
      g/L (0.276 +/- 0.006) were more than that of the control group (0.249 +/- 0.006)
      at 3 d(P < 0.01). ALP detection proved that ALP activity of MTA at 3 d (0.217 +/-
      0.008), 5 d (0.253 +/- 0.005) , 7 d (0.279 +/- 0.004) were more than that of the
      control group at 3 d (0.166 +/- 0.006) ,5 d (0.221 +/- 0.006), 7 d (0.242 +/-
      0.004) (P < 0.01). Collagen I detection showed that the level of collagen I of
      MTA at 3 d[(78.46 +/- 2.72) ug/L], 5 d[(90.73 +/- 3.08) ug/L] were more than that
      of the control group at 3 d[ (66.75 +/- 3.08) ug/L], [5 d (74.27 +/- 3.50) ug/L]
      (P < 0.01). CONCLUSIONS: MTA of high concentrations can significantly inhibit
      cell growth, and of low concentrations can promote cells proliferation and
      differentiation.

PMID- 24120003
TI  - [The 7th National Conference of the Chinese Academy of Pediatric Dentistry].

PMID- 24120004
TI  - [Clinical application of condylectomy via intraoral approach under computer
      assisted surgical navigation].
AB  - OBJECTIVE: To assess the application of computer assisted surgical navigation in
      condylectomy via intraoral approach and its clinical results. METHODS: Eight
      patients aged from 16 to 56 were treated by condylectomy via intraoral approach
      under computer assisted surgical navigation. There were 6 female and 2 male. The
      lesions were condyle osteoma in 3 patients, hemimandibular hyperplasia and
      condylar hyperplasia in 5 patients. Most patients had concomitant
      LeFortIosteotomy (6 cases), bilateral sagittal split ramus osteotomy (BSSRO) (5
      cases),contralateral sagittal split ramus osteotomy (SSRO) (1 cases), genioplasty
      (4 cases) and mandible contouring (6 cases) to recover the facial symmetry.
      RESULTS: All patients had good occlusion, oral function and facial symmetry after
      the operation. The average mouth opening was 38 mm before operation, and 41 mm
      one month after operation. The temporomandibular joint(TMJ) dysfunction syndrome
      alleviated or disappeared. The follow-up period was 3-12 months, and results were
      stable. CONCLUSIONS: Computer assisted surgical navigation can precisely
      accomplish the condylectomy via intraoral approach.It causes less trauma to the
      patient than traditional condylectomy, and can better preserve the TMJ structure
      and function.

PMID- 24120005
TI  - [Preliminary evaluation of clinical effect of computer aided design and computer
      aided manufacture zirconia crown].
AB  - OBJECTIVE: To evaluate clinical effects of computer aided design and computer
      aided manufacturing (CAD/CAM) milled zirconia crown in three aspects: aesthetic,
      contact wear and fracture. METHODS: Sixty patients were divided into two
      groups.In one group, 35 full contour CAD/CAM zirconia crown were made on molars
      of 30 patients. The manufacturing process of zirconia crown was as follow. First,
      the three dimensional(3-D) data of working models, antagonist impression and
      check records were acquired by 3-D laser scanning Dental wings S50. Then full
      contour zirconia crowns, which had functional occlusal contacts with antagonistic
      teeth, and appropriate contact with adjacent teeth were designed with Zeno
      CAD(V4.2.5.5.12919) software. ZENOSTAR Zr pure zirconia material was milled in
      digital controlled machine WIELAND 4030 M1.In the end, the zirconia crown were
      completed with the method of second sintering and polishing. After clinical try
      in, the crown was cemented.In the control group, thirty gold alloy full crown
      were made and cemented on molars of 30 patients. According to the modified U S
      Public Health Service Criteria(USPHS) evaluation standard, all crowns were
      evaluated on the same day, at three months, half a year, one year and two years
      following delivery. There were three aspects we were focusing on in the
      evaluation: aesthetic, contact wear(restoration and antagonist), and fracture.
      RESULTS: In all the prosthesis we evaluated during the 24 months, no fracture was
      found. Contact wear of crowns varies according to different antagonist teeth.
      CONCLUSIONS: The zirconia crowns show privilege in aesthesis, toughness and anti
      wearing.However, there is contact wear on antagonistic natural teeth. Thus it is
      a good choice when full zirconia crowns are indicated on two antagonistic teeth
      in both jaws.

PMID- 24120006
TI  - [Evaluation of the prevalence of the maxillary molars with two palatal roots by
      cone-beam CT].
AB  - OBJECTIVE: To investigate the characteristic of the maxillary molars with two
      palatal roots and its prevalence by cone-beam computered tomography. METHODS:
      Cone-beam CT (CBCT) images of dentitions were collected retrospectively from 528
      patients comprising 1957 maxillary molars. The characteristic and prevalence of
      maxillary molars with two palatal roots was analyzed. The tooth position, sex and
      unilateral and bilateral occurrence were recorded. RESULTS: The prevalence of two
      palatal roots was 0.72%(14/1957). Maxillary second molar with two palatal roots
      was detected in 1.12%(11/979), which showed a statistically higher prevalence
      than maxillary first molar 0.31%(3/978). This prevalence did not differ with sex
      or the side(P > 0.05). The mean distance of interorifice from the mesiolpalatal
      canal to the distopalatal canal was (2.84 +/- 0.50) mm, and the angle between two
      palatal roots was on average (34.6 +/- 16.1)  degrees ,which were significantly
      greater than the mean distance of interorifice from the two buccal roots (2.15 +/
      0.82) mm and the angle between the two roots was (21.3 +/- 12.2)  degrees .
      CONCLUSIONS: The prevalence of maxillary second molars with two palatal roots was
      higher than that of the first malars. The angle between the two palatal roots
      brings difficulty to root canal therapy, so the consciousness of double palatal
      roots of maxillary molars was helpful for clinical operation.

PMID- 24120007
TI  - [Normal occlusion study: using T-Scan III occlusal analysis system].
AB  - OBJECTIVE: To investigate the normal occlusal force distribution and the
      characteristics of the occlusion time at different occlusion position using T
      Scan III occlusal analysis system. METHODS: Fifty-three volunteers with normal
      occlusion, including 29 males and 24 females, were included in this study. The
      average age was (25.9 +/- 2.1) years old. T-Scan III occlusal analysis system was
      used to measure the occlusal force distribution and the time character of normal
      occlusion at intercuspal position, protrusive position, and lateral excursive
      position. RESULTS: At intercuspal position the left and right side molar teeth
      took the most part of force percentage, followed by (13.3 +/- 4.3)%, (13.6 +/-
      5.4)%, (15.7 +/- 7.1)%, (18.7 +/- 7.5)% (6, 6, 7, 7); and 7654, 4567 took (61.3
      +/- 12.4)% force percentage; and the left and right sides took the respective
      percentages of (46.4 +/- 7.0)%, (53.6 +/- 7.0)%, the left side was significantly
      less than the right side(P < 0.05). At the protrusion position the region ( 21,
      12) commitment to take the percentage of (85.1 +/- 25.5)%. At left and right
      lateral position, 28% (13/46) and 30%(14/46) were cuspid-protected occlusion, and
      33%(15/46) and 44%(20/46) were group functional occlusion, and 39%(18/46) and
      26%(12/46) were multiple-protected occlusion. The average occlusion time was
      (0.34 +/- 0.11) s, and disclusion time was (1.00 +/- 0.39) s. CONCLUSIONS: At
      intercuspal position the region from first premolar to second molar teeth were
      the occlusal force centers, and the second molar is the most;.the force
      concentrated in the area ( 21, 12) at the protrusion position. The lateral
      occlusal pattern is multiformity.

PMID- 24120008
TI  - [Effect of different molarity cathepsins specific inhibitor E-64 on dentin-resin
      bonding durability].
AB  - OBJECTIVE: To investigate, in vitro, the effect of cathepsins specific inhibitor
      N-(trans-epoxysuccinyl)-L-leucine 4-guanidinobutylamide(E-64) on dental
      endogenous cathepsins and to find its most effective molarity to elevate dentin
      resin bonding durability. METHODS: Fifty recently extracted human third molars
      were divided into five groups according to random number table, and treated with
      different molarity of E-64 as follow: 0, 2.5, 5.0, 10.0 and 20.0 umol/L. The
      group 0 umol/L was control group. Then 20 specimens of dentin-resin composite
      were fabricated in each group. Half of the specimens were tested after 24 h water
      storage(37  degrees C) and the other half were tested after 90 days water
      storage(37  degrees C) followed by 3000 cycles'thermocyling(5-55  degrees C) as
      aging treatment. Fractured specimens were analyzed using scanning electron
      microscopy(SEM). RESULTS: After 24 h water storage, no significant differences
      were found in micro-tensile bond strength(uTBS) of samples between different
      groups (P > 0.05). However, after ageing treatment, uTBS of the samples in group
      2.5, 5.0, 10.0 and 20.0 umol/L [(18.7 +/- 2.7), (20.8 +/- 3.4), (18.3 +/- 2.8)
      and (19.1 +/- 2.7) MPa] were significantly higher than that in group 0 umol/L
      [(15.1 +/- 3.0) MPa] (P < 0.05). Only in the group 5.0 umol/L no significant
      difference was found between the original and the decreased value of uTBS(P >
      0.05), while the uTBS in other groups decreased significantly after aging
      treatment(P < 0.05). Failure types were almost adhesive and mixed types.
      Collagens in hybrid layer were less degraded in the groups using E-64 after aging
      treatment than control group. CONCLUSIONS: E-64 was effective on inhibiting
      cathepsins activity in dentin, and induced less collagens degradation in smear
      layer for better dentin-resin bond durability.

PMID- 24120009
TI  - [Role of CD(+)4T lymphocyte subsets in the immunopathogenesis of periodontal
      disease].

PMID- 24120010
TI  - [MicroRNA in oral squamous cell carcinoma].

PMID- 24120011
TI  - Influence of ammonia on silver nanoparticle dissolution and toxicity to
      Nitrosomonas europaea.
AB  - Nitrosomonas europaea, a model ammonia oxidizing bacterium, was sensitive to both
      ionic silver (Ag(+)) and 20 nm citrate capped silver nanoparticles (AgNPs). AgNP
      toxicity has been previously shown to be primarily due to the dissolution of
      Ag(+). The rate of AgNP dissolution dramatically increased in test medium
      containing ammonium sulfate ((NH4)2SO4) and HEPES buffer compared to test medium
      containing either deionized water or HEPES buffer alone. The AgNP dissolution
      rates accelerated with increases in ammonia (NH3) concentrations either through
      increases in pH or through higher (NH4)2SO4 concentrations. Ammonia likely
      participated in the oxidation of the AgNP to form [Formula: see text] in solution
      leading to the observed increase in AgNP dissolution rates. AgNP toxicity was
      enhanced as NH3 concentrations increased. However, Ag(+) toxicity was constant at
      all NH3 concentrations tested. Therefore, it can be concluded that the increased
      AgNP toxicity was due to increased Ag(+) release and not due to a synergistic
      effect between NH3 and Ag(+). The results of this study may provide insights in
      the fate and toxicity of AgNPs in high NH3 environments including wastewater
      treatment plants, eutrophic waterways and alkaline environments.

PMID- 24120012
TI  - Dioxins levels in breast milk of women living in Caserta and Naples: assessment
      of environmental risk factors.
AB  - Naples and Caserta provinces are extensively affected by the illegal dumping of
      hazardous and urban wastes, which were periodically set to fire. Several studies
      were made on the possible health impact of this illegal waste management. The aim
      of the study was to detect dioxins levels in breast milk of volunteer primiparae
      and to assess the possible source of dioxins in the affected areas. The authors
      determined dioxins levels in breast milk from 100 primiparae from the study area
      and collected anamnestic information on donors. We determined dioxins levels in
      breast milk from 100 primiparae from the study area and collected anamnestic
      information on donors. As a measure of environmental risk of dioxins (EDR) we
      used the interpolated values of dioxins concentration in buffalo milk samples
      collected in the study area. Correlations between the EDR, age of the mother,
      smoking habit, cheese consumption, occupation in activity at risk, presence of
      plants for the disposal of toxic waste or illegal burning of solid waste near the
      residence of the donor and dioxin level in breast milk were investigated. The
      dioxin level in breast milk is significantly correlated to the EDR, the age of
      the sampled women and the presence of illegal burning of solid waste. 

PMID- 24120013
TI  - Destruction and formation of dioxin-like PCBs in dedicated full scale waste
      incinerators.
AB  - Destruction and formation of dioxin-like PCBs in full scale waste incinerators is
      studied by analysing input waste streams and boiler and fly ash of a grate
      furnace incinerator (GFI) incinerating MSW, of a Fluidised Bed Combustor (FBC)
      incinerating a mix of 50% sludge, 25% refuse derived fuel (RDF) and 25%
      automotive shredder residue (ASR) and of a rotary kiln incinerator (RKI)
      incinerating hazardous waste. The dioxin-like PCB fingerprints of the waste
      inputs show that PCB oils Aroclor 1242 and Aroclor 1254 late are the major dioxin
      like PCB contamination source of sludge, RDF and ASR. The dioxin-like PCB
      fingerprints of the waste inputs are clearly different from the fingerprints of
      the outputs, i.e. boiler and fly ash, indicating that in full scale waste
      incinerators dioxin-like PCBs in the input waste are destroyed and other dioxin
      like PCBs are newly formed in the post combustion zone. The dioxin-like PCB
      fingerprint of boiler and fly ash of all three incinerators corresponds well to
      the fly ash fingerprint obtained in lab scale de novo synthesis experiments,
      indicating that dioxin-like PCBs are mainly formed through this mechanism. The
      high PCB concentration in the input waste mix of the RKI does not promote the
      formation of dioxin-like PCBs through precursor condensation. 

PMID- 24120014
TI  - Iron species in layered clay: efficient electron shuttles for simultaneous
      conversion of dyes and Cr(VI).
AB  - The simultaneous reduction of Chromium(VI) (Cr(VI)) and oxidation of cationic
      dyes in dispersions of Montmorillonite K10 (MK10) were examined under visible
      irradiation (lambda>420 nm). The iron species (i.e. iron oxides, structural iron
      and exchangeable interlayer iron) in layered clays are active for catalytically
      reducing Cr(VI) by using Malachite green (MG) and Rhodamine B (RhB) as the
      electron donors. Molecular oxygen does not have a significant effect on clay
      catalyzed Cr(VI) reduction, but is important for oxidative degradation of dye
      pollutants. MK10 catalysts are stable and reusable, and are therefore considered
      as a promising naturally-abundant material for decontamination of dye and heavy
      metals.

PMID- 24120015
TI  - Characterization of the Danube River sediments using the PMF multivariate
      approach.
AB  - Chemical composition data for the Danube River and its tributaries sediments were
      analyzed using positive matrix factorization (PMF). The objective was to identify
      both natural and anthropogenic sources affecting Danube Basin. During the Joint
      Danube Survey 2 (JDS2) campaign 148 bottom sediments samples were collected. The
      following elements were analyzed using the X-ray fluorescence technique: Al, As,
      Ca, Cd, Cl, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, S, Si, Ti, V and Zn.
      Mercury was determined by cold vapour atomic absorption spectrometry. Three
      factors were obtained considering the whole dataset (Danube and tributaries),
      identified as: (i) carbonate component characterized by Ca and Mg; (ii) alumino
      silicate component dominated by Si and Al content and the presence of some metals
      attributed to natural processes; (iii) anthropogenic source identified by Hg, S,
      P and some heavy metals load. To better characterize the role of tributaries, the
      Danube and tributaries datasets, were also analyzed separately. The same three
      factor structures were identified in the Danube dataset. For the tributaries, a
      four-factor source model gave one further factor dominated by S and P, which
      could be attributed to the use of fertilizers in agriculture. 

PMID- 24120016
TI  - Prevalent distribution and conservation of Streptococcus suis Lmb protein and its
      protective capacity against the Chinese highly virulent strain infection.
AB  - Streptococcus suis (S. suis) is an important zoonotic pathogen that causes
      multiple diseases in both pigs and humans. Many studies suggest that
      Streptococcus utilizes host extracellular matrix proteins, including laminin, for
      adhesion and invasion of host cells. Recently, we identified a putative Lmb
      protein (CDS 0330) of a highly virulent strain of S. suis (serotype 2). In this
      study, we characterized the ability of CDS 0330 to bind human laminin, and
      evaluated the protective efficacy of a recombinant protein vaccine. Bioinformatic
      analysis revealed that both the amino acid sequence and tertiary structure of CDS
      0330 were similar to Lmb proteins in other Streptococcus. In addition, the
      sequence of CDS 0330 was present in the genomes of 26 of the 38 sequenced
      streptococci species, indicating an early origin and conservation of this gene.
      Particularly, all 17 sequenced S. suis genomes, regardless of serotype or
      geographic origin, contained CDS 0330 gene in their genome with a minimum pair
      wise amino acid identity of 92%. PCR amplification revealed that CDS 0330 gene is
      distributed throughout 35 S. suis serotypes in the lmb-htp format. Flow cytometry
      analysis confirmed that CDS 0330 was expressed on the cell surface of S. suis,
      and ELISA revealed the recombinant CDS 0330 protein could bind laminin in vitro.
      Finally, vaccinating mice with recombinant CDS 0330 protein significantly
      prolonged survival after S. suis infection. Together, these data reveal that CDS
      0330 is a laminin binding protein of S. suis 2, and open new avenues for
      preventing S. suis 2 infection. 

PMID- 24120017
TI  - Quality improvement in screening for critical congenital heart disease.
AB  - OBJECTIVES: Screening for critical congenital heart disease with pulse oximetry
      requires healthcare providers to decipher a previously published algorithm, a
      feature that raises concerns about quality of interpretation of pulse oximetry
      results. We hypothesized that this method would be prone to error and a computer
      based tool would lead to a more accurate interpretation of the screening results.
      STUDY DESIGN: In this randomized crossover study, healthcare providers with prior
      experience using pulse oximetry received 2 sets of 10 mock screening scenarios
      and were asked to interpret the results of each scenario as "pass," "fail," or
      "retest." Participants were randomized to use either the paper algorithm or
      computer-based tool for the first set of 10 scenarios and the alternative method
      for the second set. We used Wilcoxon rank sum tests to compare the accuracy of
      interpretation using the 2 methods. RESULTS: The 102 participants answered 81.6%
      of the scenarios correctly when manually interpreting the algorithm vs 98.3%
      correct when using the computer-based tool (P < .001). These differences were
      most pronounced for the "fail" scenarios (65.4% manual vs 96.7% computer, P <
      .001) and the "retest" scenarios (80.7% manual vs 98.7% computer, P < .001), but
      were also significant for the "pass" scenarios (94.1% manual vs 99.0% computer, P
      < .001). CONCLUSIONS: Use of a manual algorithm for the interpretation of results
      in screening for critical congenital heart disease with pulse oximetry is
      susceptible to human error. Implementation of a computer-based tool to aid in the
      interpretation of the results may lead to improved accuracy and quality.

PMID- 24120018
TI  - Association between birth characteristics and coronary disease risk factors among
      fifth graders.
AB  - OBJECTIVE: To evaluate the associations between selected birth characteristics
      prematurity and poor intrauterine growth-and risk factors for coronary artery
      disease detected among children enrolled in the fifth grade. STUDY DESIGN:
      Children (n = 3054) with matched birth and fifth grade health screening data on
      body mass index (BMI), systolic blood pressure, and fasting lipid profiles were
      analyzed using MANOVA with the following independent variables of weight gain by
      the fifth grade: BMI percentile, normal or overweight/obese (BMI >= 85 th
      percentile), prematurity, and intrauterine growth (ie, small for gestational age
      [SGA], appropriate for gestational age [AGA], or large for gestational age
      [LGA]). RESULTS: LGA status at birth was associated with overweight/obesity later
      in life. In fifth grade, overweight/obese children had elevated systolic blood
      pressure and abnormal levels of most fasting serum lipids compared with normal
      weight children regardless of birth characteristics. Beyond the effects of BMI
      percentile, preterm infants had higher levels of triglycerides (TG) than term
      infants by the fifth grade (P < .05). SGA infants who become overweight/obese had
      higher levels of TGs and very low-density lipoproteins compared with AGA and LGA
      infants, whether overweight or normal weight (P < .05). CONCLUSION: BMI >= 85 th
      percentile in the fifth grade is associated with abnormalities in most coronary
      artery risk factors regardless of birth characteristics. Beyond the effects of
      BMI percentile in the fifth grade, preterm infants had higher TG levels than term
      infants. SGA infants who were overweight/obese in the fifth grade had higher TG
      and very low-density lipoprotein levels compared with AGA and LGA infants who
      were overweight/obese or of normal weight in the fifth grade.

PMID- 24120019
TI  - Personal health record use and association with immunizations and well-child care
      visits recommendations.
AB  - OBJECTIVE: To determine the association of parental use of integrated personal
      health records (PHRs) with children's adherence to immunization and well-child
      care (WCC) visit recommendations. STUDY DESIGN: For the immunization and WCC
      visit measures, we retrospectively analyzed, respectively, 766 and 639 matched
      pairs at Kaiser Permanente (KP) Hawaii and 2795 and 2448 pairs at KP Northwest
      who were <= 31 days old at enrollment and continuously enrolled for 2 years
      between January 2007 and July 2011. The independent variable (>= 1 PHR feature
      used vs none) was matched using propensity scores on parental and children
      characteristics. The dependent variables were 2 measures from the 2010 Healthcare
      Effectiveness Data and Information Set: combination 2 immunization (all
      immunizations vs <all) and number of WCC visits through 15 months old (>= 6 vs
      <6). We conducted multivariate logistic, propensity score-matched regression
      adjusting for parents' education and child's continuity of care. RESULTS:
      Children whose parents used >= 1 PHR feature (vs none) had higher odds of
      adhering to the recommended immunizations only at KP Northwest (KP Hawaii: OR
      1.1, 95% CI 0.8-1.4, P > .05; KP Northwest OR 1.2, 95% CI 1.0-1.3, P < .05). PHR
      use was associated with better adherence to WCC visit recommendations for both KP
      Hawaii (OR 1.9, 95% CI 1.3-2.9, P < .001) and KP Northwest (OR 2.5, 95% CI 2.1
      2.9, P < .001). CONCLUSIONS: Young children whose parents used a PHR were more
      likely to adhere to the recommended WCC visits in both regions but immunizations
      in only 1 region.

PMID- 24120020
TI  - Intensivists at night: putting resources in the right place.
AB  - During the past 50 years, caring for the critically ill has become increasingly
      complex and the need for an intensivist has become more evident. Management by
      intensivists has become a quality indicator for many ICUs. Numerous small studies
      have demonstrated the beneficial effect of intensivists on outcomes in the
      critically ill, and some clinicians have advanced the argument that a night-time
      intensivist is essential for the care of critically ill patients. In response,
      many institutions have hired full-time intensivists for both day and night
      coverage in the ICU. Two recent studies have been conducted that make a
      compelling argument for redirecting funding of night-time intensivists to areas
      of greater need in health care. In a retrospective analysis of a large database
      that involved more than 65,000 patients, no benefit of night-time intensivists
      could be found in ICUs where care is managed by intensivists during the day. Only
      in ICUs where management by intensivists is not mandated could a beneficial
      impact on mortality be found. The second study, a randomized controlled trial,
      evaluated the effect of night-time intensivists on length of stay, mortality, and
      other outcomes and was a negative trial. In this methodologically rigorous trial,
      there was no difference in outcomes between the intensivist and control group,
      which consisted of in-house resident coverage at night with availability by
      telephone of fellows and intensivists. These two robust studies clearly suggest
      that night-time intensivists do not improve mortality in ICUs managed by
      intensivists during the day. Though possibly beneficial in low-intensity
      environments, the widespread drive to add night-time intensivist coverage may
      have been premature. 

PMID- 24120021
TI  - Comparing disease activity indices in ulcerative colitis.
AB  - BACKGROUND: Comparisons between disease activity indices for ulcerative colitis
      (UC) are few. This study evaluates three indices, to determine the potential
      impact of inter-observer variation on clinical trial recruitment or outcome as
      well as their clinical relevance. METHODS: One hundred patients with UC were
      prospectively evaluated, each by four specialists, followed by
      videosigmoidoscopy, which was later scored by each specialist. The Simple
      Clinical Colitis Activity (SCCAI), Mayo Clinic and Seo indices were compared by
      assigning a disease activity category from published thresholds for remission,
      mild, moderate and severe activity. Inter-observer variation was evaluated using
      Kappa statistics and its effect for each patient on recruitment and outcome
      measures for representative clinical trials calculated. Clinical relevance was
      assessed by comparing an independently assigned clinical category, taking all
      information into account as if in clinic, with the disease activity assigned by
      the indices. RESULTS: Inter-observer agreement for SCCAI (kappa=0.75, 95% CI 0.70
      0.81), Mayo Clinic (kappa=0.72, 95% CI 0.67-0.78) and Seo (kappa=0.89, 95% CI
      0.83-0.95) indices was good or very good as was the agreement for rectal bleeding
      (kappa=0.77) and stool frequency (kappa=0.90). Endoscopy in the Mayo Clinic index
      had the greatest variation (kappa=0.38). Inter-observer variation alone would
      have excluded up to 1 in 5 patients from recruitment or remission criteria in
      representative trials. Categorisation by the SCCAI, Mayo Clinic and Seo indices
      agreed with the independently assigned clinical category in 61%, 67% and 47% of
      cases respectively. CONCLUSIONS: Trial recruitment and outcome measures are
      affected by inter-observer variation in UC activity indices, and endoscopic
      scoring was the component most susceptible to variation.

PMID- 24120022
TI  - Successful use of agomelatine and venlafaxine combination in major depression.

PMID- 24120023
TI  - Psychiatric aspects of Wilson disease: a review.
AB  - OBJECTIVE: To review the current evidence about psychiatric symptoms in Wilson's
      disease (WD). METHOD: We searched Ovid, PsychInfo, CINHAL and PubMed databases
      from May 1946 to May 2012 using the key words Wilson('s) disease in combination
      with psychiatry, psychiatric, psychosis, schizophrenia, depression, mania,
      bipolar, mood, anxiety, personality and behavior. RESULTS: Psychiatric symptoms
      occur before, concurrent with or after the diagnosis and treatment for WD. Thirty
      to forty percent of patients have psychiatric manifestations at the time of
      diagnosis, and 20% had seen a psychiatrist prior to their WD diagnosis. When
      psychiatric symptoms preceded neurological or hepatic involvement, the average
      time between the psychiatric symptoms and the diagnosis of WD was 864.3 days. The
      prevalence of psychiatric disorders in WD patients varies wildly (major
      depressive disorder, 4-47%; psychosis, 1.4-11.3%). Certain gene mutations of
      ATP7B may correlate with specific personality traits. CONCLUSIONS: Psychiatric
      manifestations represent a significant part of the clinical presentation of WD
      and can present at any point in the course of the illness. Psychiatric
      manifestations occurring without overt hepatic or neurologic involvement may lead
      to misdiagnosis. A better understanding of the psychiatric presentations in WD
      may provide insights into the underlying mechanisms of psychiatric disorders.

PMID- 24120024
TI  - A novel fractionized sampling and stacking strategy for online hyphenation of
      solid-phase-based extraction to ultra-high performance liquid chromatography for
      ultrasensitive analysis.
AB  - We have developed a novel ultrasensitive online analytical system which
      integrated solid-phase-based extraction (SPBE) techniques with ultra-high
      performance liquid chromatography (UPLC) based on a fractionized sampling and
      stacking (FSS) strategy. FSS was proposed as a novel peak compression strategy to
      prevent band broadening and distortion caused by excessive solvents with high
      elution strength, which has been a main obstacle to conjunction of sample
      preparation techniques with UPLC. Such a strategy was based on online dividing a
      sample solution into fractions by plugs of weak mobile phase, followed by head
      column stacking process, aiming to obtain a quite sharp sample zone. FSS enables
      UPLC to tolerate much larger injection volume of solvents with high elution
      strength, which facilitates hyphenation of SPBE with UPLC without peak distortion
      or loss of sensitivity. On the basis above, an online SPBE-UPLC system was
      realized by FSS, and its applicability was preliminarily verified by the
      successful development of a sensitive solid phase extraction-FSS-UPLC method for
      the determination of triazines. Subsequently an integrated online system
      incorporating molecularly imprinted in-tube solid phase microextraction,
      derivatization and FSS-UPLC was developed for the analysis of ultra trace 24
      epibrassinolide. The developed method was ultrasensitive with detection limit as
      low as 0.7 ng/L, and the linear range of the method was 3-5000 ng/L. The
      endogenous 24-epibrassinolide in pollen, flower and seed samples was determined,
      which showed satisfactory recoveries in the range of 81.2-116% and good precision
      with relative standard deviation (RSD) values between 4.7 and 9.7%. This online
      analytical method was sensitive, reliable, rapid and applicable to trace analysis
      in complex samples.

PMID- 24120025
TI  - Trace level determination of pyrethroid and neonicotinoid insecticides in
      beebread using acetonitrile-based extraction followed by analysis with ultra-high
      performance liquid chromatography-tandem mass spectrometry.
AB  - Beebread is among the matrices suspected of contaminating honeybee. To better
      understand this contamination, the study aimed to develop an efficient, sensitive
      and reliable analytical method for the trace analysis of pesticides in beebread.
      This study focuses specifically on the insecticides pyrethroids and
      neonicotinoids and some of their metabolites. It describes the development and
      validation of an original analytical approach that consists of one simple
      extraction method based on modified QuEChERS followed by a selective and
      sensitive analysis by UHPLC-MS/MS to determine the target compounds in beebread.
      The method was validated using a quadratic fit. RSD values below 20% were
      obtained, except for 5-hydroxy-imidacloprid and imidacloprid at 0.5 ng/g, which
      exhibited RSDs of 25% and 21%, respectively. The intra-day precision was less
      than 10% for many of the investigated compounds. The inter-day precision varied
      between 2% and 36%, depending on the compound and the concentration. The
      recoveries varied from 53% to 119%, with averages of 83, 81 and 77% for the
      extraction of beebread samples spiked at 0.5, 5 and 10 ng/g, respectively. The
      LOD values for all the substances were below ng/g, with the exception of 6
      chloronicotinic acid (LOD=1.7 ng/g). The method was then applied to the analysis
      of 32 beebread samples and revealed the presence of 7 of the target substances.
      The most frequently detected pesticides belonged to the neonicotinoid family and
      were generally present at low concentrations, but in some cases exceeded 170 ng/g
      (acetamiprid and thiacloprid). Some pyrethroids were also detected (lambda
      cyhalothrine and bifenthrine), but at very low levels.

PMID- 24120026
TI  - A magnetic sorbent for the efficient and rapid extraction of organic
      micropollutants from large-volume environmental water samples.
AB  - A magnetic solid-phase extraction (MSPE) method based on a novel magnetic sorbent
      was proposed for the extraction of target compounds from large-volume water
      samples. First, magnetic hypercrosslinked microspheres (NAND-1) were prepared via
      membrane emulsification-suspension polymerization and post crosslinking reaction.
      To ensure that the Fe3O4 nanoparticles could completely pass through the membrane
      without blocking the pores, oleic acid was used to modify the Fe3O4
      nanoparticles, which enhanced lipophilicity and monodispersity of the magnetite
      nanoparticles. The obtained NAND-1 microspheres exhibited super paramagnetic
      characteristics and excellent magnetic responsiveness with a saturation
      magnetization of 2.53 emu/g. In addition, a uniform particle size (~8 MUm) and a
      large average surface area (1303.59 m(2)/g) were also observed, which were both
      beneficial for the extraction of the target compounds. Thus, NAND-1 has the
      potential to simultaneously exhibit good extraction efficiencies toward different
      types of organic micropollutants (OMPs), including triazines, carbamazepine and
      diethyl phthalate. The conditions of the MSPE based on NAND-1 were optimized by
      single factor and orthogonal design experiments. This MSPE method needed only a
      small amount of sorbent (50mg/L) for the extraction of OMPs from a large-volume
      aquatic sample (5L) and reached equilibrium in a short amount of time (30 min).
      Moreover, the solution volume, the pH, and the salinity had insignificant
      influences on the extraction of the eight target OMPs. Under the optimum
      conditions, the recoveries of the eight OMPs calculated by analyzing the spiked
      samples were from 91.7% to 99.4%. The NAND-1 could be recycled ten times and
      still achieve recoveries of the eight OMPs higher than 86%. The limits of
      detection of the eight OMPs ranged from 1.76 to 27.56 ng/L, and the limits of
      quantification were from 5.71 to 92.05 ng/L. These results indicated that the
      proposed method, based on the use of NAND-1 as a magnetic sorbent, has the
      advantages of convenience and high efficiency and can be successfully applied to
      analyze the OMPs in real water samples.

PMID- 24120027
TI  - A new ultrahigh performance liquid chromatography with diode array detection
      coupled to electrospray ionization and quadrupole time-of-flight mass
      spectrometry analytical strategy for fast analysis and improved characterization
      of phenolic compounds in apple products.
AB  - A new, rapid, selective and sensitive ultrahigh performance liquid chromatography
      with diode array detection coupled to electrospray ionization and quadrupole time
      of-flight mass spectrometry (UHPLC-DAD-ESI-Q-ToF-MS) strategy using automatic and
      simultaneous acquisition of exact mass at high and low collision energy, MS(E),
      has been developed to obtain polyphenolic profile of apples, apple pomace and
      apple juice from Asturian cider apples in a single run injection of 22 min. MS(E)
      spectral data acquisition overcomes chromatographic co-elution problems,
      performing simultaneous collection of precursor ions as well as other ions
      produced as a result of their fragmentation, which allows resolving complex
      spectra from mixtures of precursor ions in an unsupervised way and eases their
      interpretation. Using this technique, 52 phenolic compounds of five different
      classes were readily characterized in these apple extracts in both positive and
      negative ionization modes. The spectral data for phenolic compounds obtained
      using this acquisition mode are comparable to those obtained by conventional LC
      MS/MS as exemplified in this work. Among the 52 phenolic compounds identified in
      this work, 2 dihydrochalcones and 3 flavonols have been tentatively identified
      for the first time in apple products. Moreover, 2 flavanols, 4 dihydrochalcones,
      9 hydroxycinnamic acids and 4 flavonols had not been previously reported in apple
      by ToF analysis to our knowledge.

PMID- 24120028
TI  - [Perinatal health in France: an average position in Europe with a few worrying
      differences].

PMID- 24120029
TI  - Disentangling the cognitive components supporting Austin Maze performance in left
      versus right temporal lobe epilepsy.
AB  - Neuropsychological tests requiring patients to find a path through a maze can be
      used to assess visuospatial memory performance in temporal lobe pathology,
      particularly in the hippocampus. Alternatively, they have been used as a task
      sensitive to executive function in patients with frontal lobe damage. We measured
      performance on the Austin Maze in patients with unilateral left and right
      temporal lobe epilepsy (TLE), with and without hippocampal sclerosis, compared to
      healthy controls. Performance was correlated with a number of other
      neuropsychological tests to identify the cognitive components that may be
      associated with poor Austin Maze performance. Patients with right TLE were
      significantly impaired on the Austin Maze task relative to patients with left TLE
      and controls, and error scores correlated with their performance on the Block
      Design task. The performance of patients with left TLE was also impaired relative
      to controls; however, errors correlated with performance on tests of executive
      function and delayed recall. The presence of hippocampal sclerosis did not have
      an impact on maze performance. A discriminant function analysis indicated that
      the Austin Maze alone correctly classified 73.5% of patients as having right TLE.
      In summary, impaired performance on the Austin Maze task is more suggestive of
      right than left TLE; however, impaired performance on this visuospatial task does
      not necessarily involve the hippocampus. The relationship of the Austin Maze task
      with other neuropsychological tests suggests that differential cognitive
      components may underlie performance decrements in right versus left TLE. 

PMID- 24120030
TI  - Sudden unexpected death in epilepsy: small RNAs raise expectations.

PMID- 24120031
TI  - Effects of symbiotic food consumption in diabetic patients.

PMID- 24120032
TI  - Energy-restricted, n-3 polyunsaturated fatty acids-rich diet improves the
      clinical response to immuno-modulating drugs in obese patients with plaque-type
      psoriasis: a randomized control clinical trial.
AB  - BACKGROUND & AIMS: Low-grade systemic inflammation associated with obesity may
      worsen the clinical course of psoriasis. This study aimed to assess the
      effectiveness of an energy-restricted diet, enriched in n-3 polyunsaturated fatty
      acids (PUFAs) and poor in n-6 PUFAs, on metabolic markers and clinical outcome of
      obese patients with psoriasis. METHODS: Forty-four obese patients with mild-to
      severe plaque-type psoriasis treated with immuno-suppressive drugs were
      randomized to assume for six months either their usual diet or an energy
      restricted diet (20 kcal/kg/ideal body weight/day) enriched of n-3 PUFAs (average
      2.6 g/d). All patients continued their immuno-modulating therapy throughout the
      study. RESULTS: At 3 and 6 months, a significant clinical improvement was
      observed in patients assuming the low-calorie high n-3 PUFAs diet respect to
      controls. Specifically Psoriasis Area Score Index (7.7 +/- 3.7, 5.3 +/- 4.3 and
      2.6 +/- 3.0, respectively; p < 0.05), itch scores (15.4 +/- 13.5, 12.3 +/- 12.1
      and 1.8 +/- 5.9, respectively; p < 0.05) and Dermatological Life Quality Index
      (19.5 +/- 1.9, 11.4 +/- 3.5 and 5.1 +/- 1.6; respectively, p < 0.05) all
      decreased respect to baseline. In these subjects but not in controls, a
      significant decrease in body weight (93.8 +/- 10.1, 85.8 +/- 11.4 and 83.1 +/-
      12.1 kg, respectively; p < 0.05), waist circumference (112.7 +/- 7.2, 106.1 +/-
      10.3 and 101.9 +/- 10.4 cm; p < 0.05), serum triglycerides (141.8 +/- 51.1, 100.5
      +/- 26.6 and 90.2 +/- 34.5 mg/dL; respectively, p < 0.05), serum total
      cholesterol (198.3 +/- 31.7, 171.4 +/- 29.0 and 176.5 +/- 20.5 mg/dL;
      respectively, p < 0.05) and n-6/n-3 ratio intake also occurred (5.1 +/- 0.9, 2.0
      +/- 0.9 and 2.3 +/- 1.1; respectively, p < 0.05). CONCLUSIONS: In obese psoriatic
      patients, an energy-restricted diet designed to increase n-3 and reduce n-6
      PUFAs, ameliorated the metabolic profile and, by increasing the response to
      immuno-modulating therapy, improved the clinical outcomes of the disease
      (ClinicalTrials.gov identifier: NCT01876875).

PMID- 24120033
TI  - Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics.
AB  - During the cellular oxidation of fuels, electrons are used to power the proton
      pumps of the mitochondrial electron transport chain (ETC) and ultimately drive
      ATP synthesis and the reduction of molecular oxygen to water. During these
      oxidative processes, some electrons can 'spin off' during fuel oxidation and
      electron transport to univalently reduce O2, forming reactive oxygen species
      (ROS). In excess, ROS can be detrimental; however, at low concentrations
      oxyradicals are essential signaling molecules. Mitochondria thus use a battery of
      systems to finely control types and levels of ROS, including antioxidants.
      Several antioxidant systems depend on glutathione. Here, we review mitochondrial
      ROS homeostatic systems, including emerging knowledge about roles of glutathione
      in redox balance and the control of protein function by post-translational
      modification. 

PMID- 24120034
TI  - Recent advances in reactive oxygen species measurement in biological systems.
AB  - Reactive oxygen species (ROS) play an essential role in facilitating signal
      transduction processes within the cell. However, the precise details of the redox
      dynamics involved are not well understood. The generation of ROS is tightly
      controlled both spatially and temporally within the cell, making the study of ROS
      dynamics particularly difficult. In order to measure these dynamics, precise
      tools that can specifically examine the relevant ROS are required. Recent
      advancements in methodologies for ROS measurement have allowed the study of ROS
      biology at a level of precision previously unachievable. Here, we discuss
      improvements to fluorescent ROS dye technologies, genetically encoded ROS
      reporters, nanoparticle delivery systems, and nanotube ROS probes. These
      technologies improve specificity, localization and sensitivity over previously
      available ROS probes. 

PMID- 24120035
TI  - DNA barcoding detects contamination and substitution in North American herbal
      products.
AB  - BACKGROUND: Herbal products available to consumers in the marketplace may be
      contaminated or substituted with alternative plant species and fillers that are
      not listed on the labels. According to the World Health Organization, the
      adulteration of herbal products is a threat to consumer safety. Our research
      aimed to investigate herbal product integrity and authenticity with the goal of
      protecting consumers from health risks associated with product substitution and
      contamination. METHODS: We used DNA barcoding to conduct a blind test of the
      authenticity for (i) 44 herbal products representing 12 companies and 30
      different species of herbs, and (ii) 50 leaf samples collected from 42 herbal
      species. Our laboratory also assembled the first standard reference material
      (SRM) herbal barcode library from 100 herbal species of known provenance that
      were used to identify the unknown herbal products and leaf samples. RESULTS: We
      recovered DNA barcodes from most herbal products (91%) and all leaf samples
      (100%), with 95% species resolution using a tiered approach (rbcL + ITS2). Most
      (59%) of the products tested contained DNA barcodes from plant species not listed
      on the labels. Although we were able to authenticate almost half (48%) of the
      products, one-third of these also contained contaminants and or fillers not
      listed on the label. Product substitution occurred in 30/44 of the products
      tested and only 2/12 companies had products without any substitution,
      contamination or fillers. Some of the contaminants we found pose serious health
      risks to consumers. CONCLUSIONS: Most of the herbal products tested were of poor
      quality, including considerable product substitution, contamination and use of
      fillers. These activities dilute the effectiveness of otherwise useful remedies,
      lowering the perceived value of all related products because of a lack of
      consumer confidence in them. We suggest that the herbal industry should embrace
      DNA barcoding for authenticating herbal products through testing of raw materials
      used in manufacturing products. The use of an SRM DNA herbal barcode library for
      testing bulk materials could provide a method for 'best practices? in the
      manufacturing of herbal products. This would provide consumers with safe, high
      quality herbal products.

PMID- 24120036
TI  - Lack of association between the LPR and VNTR polymorphisms of the serotonin
      transporter gene and cocaine dependence in a Spanish sample.
AB  - We genotyped the LPR and VNTR polymorphisms of the serotonin transporter gene in
      504 cocaine-dependent patients and 508 controls. No association was detected with
      either polymorphism or with any haplotype combination. This study provided no
      evidence that these polymorphisms confer susceptibility to cocaine dependence in
      our sample. 

PMID- 24120038
TI  - Peptide-based MRI contrast agent and near-infrared fluorescent probe for
      intratumoral legumain detection.
AB  - Recent studies suggest that intratumoral legumain promotes tumorigenesis. To
      monitor legumain activity in tumors, we developed a new MRI contrast agent ([Gd
      NBCB-TTDA-Leg(L)]) and a NIR fluorescence probe (CyTE777-Leg(L)-CyTE807). The MRI
      contrast agent was prepared by introduction of cyclobutyl and benzyl group
      residues to TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triaza-dodecanedioic acid),
      followed by the attachment of a legumain-specific substrate peptide (Leg(L)). The
      NIR fluorescence probe was designed by conjugating two NIR fluorochromes (CyTE777
      and CyTE807) with Leg(L). Peptide cleavage of the MRI contrast agent by legumain
      can increase its hydrophobicity and promote rotational correlation time (tau(R)).
      Peptide cleavage of the NIR probes by the legumain relieves the self quench of
      the probe. Peptide cleavage of the MRI contrast agent and the NIR fluorescence
      probe by legumain were confirmed by T1 relaxometric studies and by fluorescence
      studies, respectively. In vivo MR images showed that [Gd-NBCB-TTDA-Leg(L)]
      attained 55.3 fold (254.2% versus 4.6%, at 2.0 h post-injection) higher imaging
      enhancement, as compared with control contrast agent bearing a noncleaveable
      peptide ([Gd-NBCB-TTDA-Leg(D)], in the CT-26 (legumain(+)) tumors. Similarly,
      optical imaging probe CyTE777-Leg(L)-CyTE807 attained 15.2 fold (3.34 * 10(9)
      photons/min versus 0.22 * 10(9) photons/min, at 24.0 h post-injection) higher
      imaging enhancement in the CT-26 (legumain(+)) tumors, compared to a NIR control
      probe (CyTE777-Leg(D)-CyTE807). These data indicate that the [Gd-NBCB-TTDA
      Leg(L)] and the CyTE777-Leg(L)-CyTE807 probes may be promising tools to image the
      legumain-expressing cancers for diagnoses and targeted treatments.

PMID- 24120037
TI  - Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.
AB  - Changes in tissue and organ stiffness occur during development and are frequently
      symptoms of disease. Many cell types respond to the stiffness of substrates and
      neighboring cells in vitro and most cell types increase adherent area on stiffer
      substrates that are coated with ligands for integrins or cadherins. In vivo cells
      engage their extracellular matrix (ECM) by multiple mechanosensitive adhesion
      complexes and other surface receptors that potentially modify the mechanical
      signals transduced at the cell/ECM interface. Here we show that hyaluronic acid
      (also called hyaluronan or HA), a soft polymeric glycosaminoglycan matrix
      component prominent in embryonic tissue and upregulated during multiple
      pathologic states, augments or overrides mechanical signaling by some classes of
      integrins to produce a cellular phenotype otherwise observed only on very rigid
      substrates. The spread morphology of cells on soft HA-fibronectin coated
      substrates, characterized by formation of large actin bundles resembling stress
      fibers and large focal adhesions resembles that of cells on rigid substrates, but
      is activated by different signals and does not require or cause activation of the
      transcriptional regulator YAP. The fact that HA production is tightly regulated
      during development and injury and frequently upregulated in cancers characterized
      by uncontrolled growth and cell movement suggests that the interaction of
      signaling between HA receptors and specific integrins might be an important
      element in mechanical control of development and homeostasis.

PMID- 24120039
TI  - Circumferential alignment of vascular smooth muscle cells in a circular
      microfluidic channel.
AB  - The circumferential alignment of human aortic smooth muscle cells (HASMCs) in an
      orthogonally micropatterned circular microfluidic channel is reported to form an
      in vivo-like smooth muscle cell layer. To construct a biomimetic smooth muscle
      cell layer which is aligned perpendicular to the axis of blood vessel, a half
      circular polydimethylsiloxane (PDMS) microchannel is first fabricated by soft
      lithography using a convex PDMS mold. Then, the orthogonally microwrinkle
      patterns are generated inside the half-circular microchannel by a strain
      responsive wrinkling method. During the UV treatment on a PDMS substrate with
      uniaxial 40% stretch and a subsequent strain releasing step, the microwrinkle
      patterns perpendicular to the axial direction of the circular microchannel are
      generated, which can guide the circumferential alignment of HASMCs during
      cultivation. The analysis of orientation angle, shape index, and contractile
      protein marker expression indicates that the cultured HASMCs reveal the in vivo
      like cell phenotype. Finally, a fully circular microchannel is produced by
      bonding two half-circular microchannels, and the HASMCs are cultured
      circumferentially inside the channels with high alignment and viability for 5
      days. These results demonstrated the creation of an in vivo-like 3D smooth muscle
      cell layer in the circular microfluidic channel which can provide a bioassay
      platforms for in-depth study of HASMC biology and vascular function.

PMID- 24120040
TI  - Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG
      lipid nanoparticles.
AB  - The translation of experimental stroke research from the laboratory to successful
      clinical practice remains a formidable challenge. We previously reported that
      PEGylated-lipid nanoparticles (PLNs) effectively transport across the blood-brain
      barrier along with less inflammatory responses. In the present study, PLNs
      conjugated to Fas ligand antibody that selectively present on brain ischaemic
      region were used for therapeutic targeting. Fluorescent analysis of the mice
      brain show that encapsulated 3-n-Butylphthalide (dl-NBP) in PLNs conjugated with
      Fas ligand antibody effectively delivered to ipsilateral region of ischaemic
      brain. Furthermore, the confocal immunohistochemical study demonstrated that
      brain-targeted nanocontainers specifically accumulated on OX42 positive microglia
      cells in ischaemic region of mice model. Finally, dl-NBP encapsulated nano-drug
      delivery system is resulted in significant improvements in brain injury and in
      neurological deficit after ischaemia, with the significantly reduced dosages
      versus regular dl-NBP. Overall, these data suggests that PLNs conjugated to an
      antibody specific to the Fas ligand constituted an ideal brain targeting drug
      delivery system for brain ischaemia. 

PMID- 24120041
TI  - The effect of serum in culture on RNAi efficacy through modulation of polyplexes
      size.
AB  - Serum in the culture medium is one crucial factor that compromises RNAi
      efficiency of non-viral vectors. However, mechanistic roles of serum in siRNA
      delivery remain unknown. In this work, we took one cationic polymer, pullulan
      chemically modified by spermine (termed as pullulan-spermine, Ps), as a siRNA
      carrier model to investigate the effects of serum on key steps in siRNA delivery
      including formation of Ps and siRNA polyplexes (Ps-siRNA), cellular uptake,
      lysosomal escape, and cytotoxicity. We demonstrate that low serum concentration
      (1.25% and 2.5%) in culture medium results in large particles of Ps-siRNA, while
      high serum concentration (10%-40%) leads to small particles of Ps-siRNA. The
      larger particles initiated the internalization of siRNA more effectively in
      comparison to the smaller ones. The engulfed Ps-siRNA particles mainly locate in
      lysosomes. The large particles exhibited stronger abilities of destabilizing
      lysosomes than that of the small particles as large Ps-siRNA particles contain
      more amines and subsequently elicit a stronger proton sponge effect which results
      in more effective lysosomal escape of siRNA. Despite the lower RNAi efficiency,
      the small particle of Ps-siRNA in the high serum medium generates much lower
      cytotoxicity. These findings explain why serum significantly affects RNAi and
      also propose a strategy for improving RNAi efficiency and safety by modulating
      serum concentration and enhancing lysosomal destabilization. 

PMID- 24120042
TI  - Experimental characterisation for micromechanical modelling of CoCr stent
      fatigue.
AB  - Fatigue of CoCr alloy stents has become a major concern in recent times, owing to
      cases of premature fracture, often driven by microstructural phenomena. This work
      presents the development of a micromechanical framework for fatigue design, based
      on experimental characterisation of a biomedical grade CoCr alloy, including both
      microscopy and mechanical testing. Fatigue indicator parameters (FIPs) within the
      micromechanical framework are calibrated for the prediction of microstructure
      sensitive fatigue crack initiation (FCI). A multi-scale CoCr stent model is
      developed, including a 3D global J2 continuum stent-artery model and a 2D
      micromechanical sub-model. Several microstructure realizations for the stent sub
      model allow assessment of the effect of crystallographic orientations on stent
      fatigue crack initiation predictions. Predictions of FCI are compared with
      traditional Basquin-Goodman total life predictions, revealing more realistic
      scatter of data for the microstructure-based FIP approach. Comparison of stent
      predictions with performance of a 316L stent for the same generic design exposes
      the design as over-conservative for the CoCr alloy. In response, the
      micromechanical framework is used to modify the stent design for the CoCr alloy,
      improving design efficiency. 

PMID- 24120043
TI  - Phosphorescent iridium(III) complexes as multicolor probes for specific
      mitochondrial imaging and tracking.
AB  - In the present study, four phosphorescent iridium(III) complexes [Ir(C
      N)2(PhenSe)](+) (Ir1-Ir4, in which C-N = 2-(2,4-difluorophenyl)pyridine (dfppy),
      dibenzo[f,h]quinoxaline (dbq), 2-phenylquinoline (2-pq) and 2-phenylpyridine
      (ppy), PhenSe = 1,10-phenanthrolineselenazole) with tunable emission colors were
      developed to image mitochondria and track the dynamics of the mitochondrial
      morphology. In comparison with commercially available mitochondrial trackers, Ir1
      Ir4 possess high specificity to mitochondria in live and fixed cells without
      requiring prior membrane permeabilization or the replacement of the culture
      medium. Due to the high resistance of Ir1-Ir4 to the loss of mitochondrial
      membrane potential as well as the appreciable tolerance to environmental changes,
      these complexes are applicable for the imaging and tracking of the mitochondrial
      morphological changes over long periods of time. In addition, Ir2-Ir4 exhibited
      superior photostability compared to the commercially available mitochondrial
      trackers. These colorful iridium(III) complexes may contribute to the future
      development of staining agents for organelle-selective imaging in living cells.

PMID- 24120045
TI  - The influence of cellular source on periodontal regeneration using calcium
      phosphate coated polycaprolactone scaffold supported cell sheets.
AB  - Cell-based therapy is considered a promising approach to achieving predictable
      periodontal regeneration. In this study, the regenerative potential of cell
      sheets derived from different parts of the periodontium (gingival connective
      tissue, alveolar bone and periodontal ligament) were investigated in an athymic
      rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC)
      and gingival margin-derived cells (GMC) were obtained from human donors. The
      osteogenic potential of the primary cultures was demonstrated in vitro. Cell
      sheets supported by a calcium phosphate coated melt electrospun polycaprolactone
      (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically
      created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL
      scaffold alone was able to promote alveolar bone formation within the defect
      after 4 weeks. The addition of ABC and PDLC sheets resulted in significant
      periodontal attachment formation. The GMC sheets did not promote periodontal
      regeneration on the root surface and inhibited bone formation within the CaP-PCL
      scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP
      PCL scaffold could promote periodontal regeneration, but ABC sheets were not as
      effective as PDLC sheets in promoting new attachment formation.

PMID- 24120044
TI  - Avidin as a model for charge driven transport into cartilage and drug delivery
      for treating early stage post-traumatic osteoarthritis.
AB  - Local drug delivery into cartilage remains a challenge due to its dense
      extracellular matrix of negatively charged proteoglycans enmeshed within a
      collagen fibril network. The high negative fixed charge density of cartilage
      offers the unique opportunity to utilize electrostatic interactions to augment
      transport, binding and retention of drug carriers. With the goal of developing
      particle-based drug delivery mechanisms for treating post-traumatic
      osteoarthritis, our objectives were, first, to determine the size range of a
      variety of solutes that could penetrate and diffuse through normal cartilage and
      enzymatically treated cartilage to mimic early stages of OA, and second, to
      investigate the effects of electrostatic interactions on particle partitioning,
      uptake and binding within cartilage using the highly positively charged protein,
      Avidin, as a model. Results showed that solutes having a hydrodynamic diameter
      <=10 nm can penetrate into the full thickness of cartilage explants while larger
      sized solutes were trapped in the tissue's superficial zone. Avidin had a 400
      fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90%
      of the absorbed Avidin remained within cartilage explants for at least 15 days.
      We report reversible, weak binding (K(D) ~ 150 MUM) of Avidin to intratissue
      sites in cartilage. The large effective binding site density (N(T) ~ 2920 MUM)
      within cartilage matrix facilitates Avidin's retention, making its structure
      suitable for particle based drug delivery into cartilage.

PMID- 24120046
TI  - Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents.
AB  - An efficient MRI T2-weighted contrast agent incorporating a potential liver
      targeting functionality was synthesized via the combination of superparamagnetic
      iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs).
      Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid
      treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified
      with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were
      subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic
      hysteresis loop indicated that the product displayed superparamagnetism at room
      temperature which was further confirmed by ZFC (zero field cooling)/FC (field
      cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic
      nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines.
      Enhanced T2 relaxivities were observed for the hybrid material (186 mM(-1) s(-1))
      in comparison with the pure magnetic nanoparticles (92 mM(-1) s(-1)) due to the
      capacity of the MWCNTs to "carry" more nanoparticles as clusters. More
      importantly, after administration of the composite material to an in vivo liver
      cancer model in mice, a significant increase in tumor to liver contrast ratio
      (277%) was observed in T2 weighted magnetic resonance images.

PMID- 24120047
TI  - Baculovirus-transduced, VEGF-expressing adipose-derived stem cell sheet for the
      treatment of myocardium infarction.
AB  - Cell sheet technology has been widely employed for the treatment of myocardial
      infarction (MI), but cell sheet fabrication generally requires the use of thermo
      responsive dishes. Here we developed a method for the preparation of adipose
      derived stem cell (ASC) sheet that obviated the need of thermo-responsive dishes.
      This method only required the seeding of rabbit ASC onto 6-well plates at an
      appropriate cell density and culture in appropriate medium, and the cells were
      able to develop into ASC sheet in 2 days. The ASC sheet allowed for transduction
      with the hybrid baculovirus at efficiencies >97%, conferring robust and prolonged
      (>35 days) overexpression of vascular endothelial growth factor (VEGF). The ASC
      sheet was easily detached by brief (10 s) trypsinization and saline wash, while
      retaining the extracellular matrix and desired physical properties. The ASC sheet
      formation and VEGF expression promoted cell survival under hypoxia in vitro.
      Epicardial implantation of the VEGF-expressing ASC sheet to rabbit MI models
      reduced the infarct size and improved cardiac functions to non-diseased levels,
      as judged from the left ventrical ejection fraction/myocardial perfusion. The
      VEGF-expressing ASC sheet also effectively prevented myocardial wall thinning,
      suppressed myocardium fibrosis and enhanced blood vessel formation. These data
      implicated the potential of this method for the preparation of genetically
      engineered ASC sheet and future MI treatment.

PMID- 24120048
TI  - Aligned neurite outgrowth and directed cell migration in self-assembled
      monodomain gels.
AB  - Regeneration of neural tissues will require regrowth of axons lost due to trauma
      or degeneration to reestablish neuronal connectivity. One approach toward this
      goal is to provide directional cues to neurons that can promote and guide neurite
      growth. Our laboratory previously reported the formation of aligned monodomain
      gels of peptide amphiphile (PA) nanofibers over macroscopic length scales. In
      this work, we modified these aligned scaffolds specifically to support neural
      cell growth and function. This was achieved by displaying extracellular matrix
      (ECM) derived bioactive peptide epitopes on the surface of aligned nanofibers of
      the monodomain gel. Presentation of IKVAV or RGDS epitopes enhanced the growth of
      neurites from neurons encapsulated in the scaffold, while the alignment guided
      these neurites along the direction of the nanofibers. After two weeks of culture
      in the scaffold, neurons displayed spontaneous electrical activity and
      established synaptic connections. Scaffolds encapsulating neural progenitor cells
      were formed in situ within the spinal cord and resulted in the growth of oriented
      processes in vivo. Moreover, dorsal root ganglion (DRG) cells demonstrated
      extensive migration inside the scaffold, with the direction of their movement
      guided by fiber orientation. The bioactive and macroscopically aligned scaffold
      investigated here and similar variants can potentially be tailored for use in
      neural tissue regeneration.

PMID- 24120049
TI  - Engineering of perfluorooctylbromide polypyrrole nano-/microcapsules for
      simultaneous contrast enhanced ultrasound imaging and photothermal treatment of
      cancer.
AB  - A versatile oil-in-water emulsion method has been explored for constructing water
      dispersible polypyrrole (PPy) nano-/microcapsules with a soluble PPy complex as
      multifunctional photothermal agents for tumor ablation. In this work, both PPy
      nanocapsules (280.4 +/- 79.0 nm) and microcapsules (1.31 +/- 0.45 MUm) with
      liquid perfluorooctylbromide (PFOB) core could be obtained by simply tuning the
      process energy for emulsion formation from ultrasonication to homogenization.
      Owing to the encapsulated liquid PFOB and strong near-infrared (NIR) absorption
      of PPy shell, the resulted PPy capsules showed great promise in ultrasound
      imaging guided photothermal ablation of tumor cells without inducing any
      significant side effect. Thus, it is anticipated that fine-tuning of the other
      encapsulated drugs or functional materials in PPy capsules would foster avenues
      for the development of multifunctional platforms for cancer treatments.

PMID- 24120050
TI  - The biomechanical effect of increased valgus on total knee arthroplasty: a
      cadaveric study.
AB  - The effects of valgus load on cadaveric knees following total knee arthroplasty
      (TKA) were investigated using a custom testing system. TKAs were performed on 8
      cadaveric knees and tested at 0 degrees , 30 degrees , and 60 degrees  knee
      flexion in both neutral and 5 degrees  valgus. Fuji pressure sensitive film was
      used to quantify contact areas and pressures and MCL strain was determined using
      a Microscribe digitizing system. Lateral tibiofemoral pressures increased (P <
      0.05) at all knee flexion angles with valgus loading. Patellofemoral contact
      characteristics did not change significantly (P > 0.05). Significant increases in
      strain were observed along the anterior and posterior border of the MCL at all
      knee flexion angles. These findings suggest that valgus loading increases TKA
      joint contact pressures and MCL strain with increasing knee flexion which may
      increase implant instability.

PMID- 24120052
TI  - Digital imaging is not superior to film-screen imaging for the detection of
      periprosthetic osteolysis around total knee arthroplasties.
AB  - Our aim was to compare the assessment of periprosthetic osteolysis around total
      knee arthroplasties using digital images against film-screen images. Simulated
      osteolytic lesions were created around 3 cadaveric total knee arthroplasties
      images acquired using fluoroscopic-assisted radiography and Computed Tomography.
      Three surgeons reviewed the film-screen images (AP/Lateral, Oblique, and Computed
      Tomography (CAT)) and the same images digitally. Combinations of 2 or more images
      that included the AP/Lateral views had superior performance in both film-screen
      and digital imaging to AP/Lateral views alone, except for the digital
      AP/Lateral/OBL combination. Lesion detection and volume appreciation were
      superior for film versus digital assessment for most angles. The addition of
      obliques to assessment using digital imaging improved performance, but film
      screen remained superior to digital imaging for assessment of periprosthetic
      osteolysis. 

PMID- 24120051
TI  - Conversion total hip arthroplasty after previous transtrochanteric rotational
      osteotomy for osteonecrosis of the femoral head.
AB  - The results of conversion total hip arthroplasty (THA) after failed
      transtrochanteric rotational osteotomy (TRO) are still controversial. We
      retrospectively reviewed 18 patients with ONFHs who had been treated previously
      by TRO and were later converted to THAs (conversion group). We made a matched
      control group of 18 primary THAs for ONFH done by same hip surgeon (PTHA group).
      There was an improvement in the Harris hip score and WOMAC score at the final
      follow-up but the improvement was not statistically significant between the two
      groups. Only internal rotation was significantly better in the PTHA group than in
      the conversion group. THA after TRO provides satisfactory clinical and
      radiological outcomes with no significant increase in perioperative morbidity in
      comparison with that in the primary THA. 

PMID- 24120053
TI  - [Attach great importance to the standardized clinical usage and safety monitoring
      of recombinant human growth hormone in children].

PMID- 24120054
TI  - [The importance of confirmative diagnosis of presymptomatic patients with
      Wilson's disease].

PMID- 24120055
TI  - [Summary of the 2012 national symposium on pediatric new drugs clinical trials].

PMID- 24120056
TI  - [Prevalence of metabolic syndrome of children and adolescent students in Chinese
      six cities].
AB  - OBJECTIVE: To investigate the prevalence of obesity and metabolic syndrome in
      Chinese children and adolescents and to evaluate clinical applications of two
      definitions of metabolic syndrome in children and adolescents developed by The
      Society of Pediatrics, Chinese Medical Association in 2012 (MS-CHN2012) and by
      International Diabetes Federation in 2007 (MS-IDF2007), respectively. METHOD:
      Totally 22 071 children (11 638 were boys and 10 433 were girls) aged 7 to 16
      years from 6 representative geographical areas, including Beijing, Tianjin,
      Hangzhou, Shanghai, Chongqing and Nanning, were surveyed in a random cluster
      sample in Chinese. Anthropometric parameters and blood pressure were determined.
      Fasting blood glucose, fasting blood triglyceride, total cholesterol, and high
      density lipoprotein cholesterol (HDL-C) levels were measured. Then non-high
      density lipoprotein cholesterol (non-HDL-C) levels were calculated. The
      diagnostic concordance of the two definitions for metabolic syndrome (MS-CHN2012
      and MS-IDF2007) and its individual components were estimated. RESULT: (1) The
      prevalence of overweight and obesity was 19.9% in 7-16-year-old teenagers and the
      prevalence of obesity was 8.9%. The prevalence of obesity in boys was higher than
      in girls (10.9% vs. 6.6%, P < 0.001). (2) The prevalence of obesity in Northern
      region (Beijing, Tianjin), Midwest region (Chongqing and Nanning) and Eastern
      region (Hangzhou, Shanghai) were significantly different (chi(2) = 1.007*10(3), P
      < 0.001), the prevalence of obesity in Northern region was the highest (16.9%),
      in Midwest was 5.9% and in the Eastern region was the lowest (4.9%). The
      prevalence of obesity in boys was higher than in girls (10.9% vs. 6.6%, P <
      0.001). (3) The prevalence of MS diagnosed by MS-CHN2012 and MS-IDF2007 in 7-16
      year-old teenagers were 2.4% and 1.4%, respectively, and in obese subjects were
      28.8% and 16.8%, respectively. The prevalence of MS diagnosed by MS-CHN2012 was
      higher than that diagnosed by MS-IDF2007 (P < 0.001). (4) The concordance between
      the two definitions for diagnosing metabolic syndrome was good (kappa = 0.711);
      as for detecting the individual components, the Kappa concordance index was
      1.000, 0.818, 0.713, 0.686 for hyperglycemia, cholesterol abnormality,
      hypertriglyceridemia and hypertension, respectively. CONCLUSION: (1) The
      prevalence of overweight and obesity was 19.9% in 7-16-year-old teenagers and the
      prevalence of obesity was 8.9%, which was higher in boys than in girls. The
      obesity of children had uneven geographical distribution and the Northern region
      was higher than the other. (2) The concordance between MS-CHN2012 and MS-IDF2007
      definitions for diagnosing metabolic syndrome in Chinese children and adolescents
      was good. Compared with MS-IDF2007 definition, MS-CHN2012 definition was more
      effective to detect high risk of MS in children and adolescents and to reduce the
      risk of the occurrence of MS in adulthood.

PMID- 24120057
TI  - [Analysis of GALNS gene mutation in thirty-eight Chinese patients with
      mucopolysaccharidosis type IVA].
AB  - OBJECTIVE: Mucopolysaccharidosis (MPS) type IVA (MPS IVA) is an autosomal
      recessive lysosomal storage disease caused by deficiency of N-acetylgalactosamine
      6-sulfate sulfatase (GALNS) needed to degrade glycosaminoglycanes (GAGs),
      accumulation of GAGs in the tissue resulting in disorder of function. So far, the
      small number of articles about clinical study of Chinese MPS IVA were published
      and only one paper about gene mutation analysis was published. This study aimed
      to investigate the mutation spectrum and characteristic of GALNS gene in Chinese
      patients with MPS IVA who were diagnosed in our hospital. METHOD: Thirty-eight
      patients from 36 families (male 17, female 21) were diagnosed as MPS IVA by GALNS
      activity determination [(0.85 +/- 1.33) nmol/(17 h.mg)] and clinical symptoms
      during 2006-2012. The average age of diagnosis was (5.7 +/- 3.6) years. Mutation
      analysis of GALNS gene performed performed by PCR-direct DNA sequencing for 38
      patients. PCR-restriction fragment length polymorphism analysis was used for
      validating novel mutation, and also to assess amino acid conservation for novel
      missense variants in five different species. PolyPhen-2 tool was used to predict
      the possible impact of missense mutations on the structure and function of the
      human GALNS protein, etc. Analysis of GALNS activity and gene mutation in
      amniotic fluid were performed to provide the prenatal diagnosis for some families
      with MPS type IVA. RESULT: (1) Thirty-eight kinds of mutation in GALNS gene were
      identified in 38 patients of them, 71% were missense mutations. p. M318R was a
      hot-spot mutation (21%) tested. Five kinds of mutation i.e., p. P163H, p.G168L,
      p. A324E, p. L366P and p. F452L were only found in Chinese patients with MPS IVA.
      Eighteen kinds of novel mutation were detected including p. E315K, p.G304D,
      p.R251Q, p.Y240C, p.G161E, p.N32D, p.L390P, p. D60E, p. P420S, W403C/T404S,
      p.L454P, for p.W405X, p. M1I, c.409_ c.420del12, c.1176_1178del3, c.1046delG,
      c.1188delG and IVS9-2A>C. (2) The polymorphism of novel missense variants were
      ruled out by the PCR-restriction fragment length polymorphism analysis and no
      related mutations were found in 50 normal controls. A splice site mutation IVS9
      2A>C had been validated by reverse transcription PCR direct sequencing. The amino
      acid of mutant position of 10 kinds of missense variants are highly conserved and
      only p. L454 is moderately conserved position. These missense variants were
      predicted to cause damage to the structure and function of human GALNS protein
      possibly according to the PolyPhen-2 tool, so these novel missense variants may
      be disease-causing mutations. (3) Prenatal diagnosis was provided for 7 families
      and three fetuses were diagnosed as MPS IVA. CONCLUSION: The GALNS gene mutation
      spectrum in Chinese patients with MPS IVA is really different from that in other
      countries, five kinds of mutation were only found in Chinese patients with MPS
      IVA. The reports of hot-spot mutation in Chinese patients were also different,
      and should be analyzed by more data of gene mutation analysis and epidemiological
      study.

PMID- 24120058
TI  - [Protective effect of cotransfection of A20 and HO-1 gene against the apoptosis
      induced by TNF-alpha in rat islets in vitro].
AB  - OBJECTIVE: To establish the method for cotransferring human A20 gene and human
      heme oxygenase-1 (HO-1) gene into the isolated rat islets using lentiviral
      transfection system, and to study the protective effect of A20 and HO-1 protein
      against the apoptosis induced by cycloheximide (CHX) and TNF-alpha, and finally
      to explore the underlying mechanism. METHOD: The A20 gene and HO-1 gene were
      cloned and inserted into the lentiviral transfection system. The efficacy of gene
      transfer was measured by the intensity of the enhanced green fluorescent protein
      (EGFP) fluorescence-positive islets. Western blot was applied to verify the
      expression of the A20 and HO-1 genes. To induce apoptosis in vitro, the isolated
      islets were treated with CHX+TNF-alpha, terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL) and the fluorescence-activated cell sorting (FACS)
      methods were used to evaluate the apoptosis of the islet cells and Western blot
      was used to detect caspase-3 activation. RESULT: (1) A20 and HO-1 genes were
      introduced into the isolated islets by lentiviral transfection, both of the genes
      were highly expressed in the islets after 96 hours culture detected by Western
      blot method. (2) The insulin levels in the cell culture medium from A20 and/or HO
      1 transgenic islets were significantly higher than that in non-transgenic
      controls (P < 0.01). (3)After CHX + TNF-alpha treatment, the cell culture medium
      insulin concentration in the A20 gene transfected group [(93.58 +/- 4.12)ug/ml],
      HO-1 gene transfected group [(88.98 +/- 4.77) ug/ml ] and A20/HO-1 co-transfected
      group [(103.33 +/- 3.16) ug/ml] were significantly higher than that in the EGFP
      group [(9.03 +/- 0.65) ug/ml ] and the control group [(8.86 +/- 0.38) ug/ml] (P <
      0.001). Minimum expression level of the activated caspase-3 was found in the
      A20/HO-1 co-transfected group. CONCLUSION: The lentiviral gene transfer system
      was an efficient and stable gene transfer vector, the over-expressed A20 and HO-1
      protein delivered via lentivirus could preserve rats' islets function and act
      against the apoptosis induced by CHX and TNF-alpha.

PMID- 24120059
TI  - [Recommendations for the clinical use of recombinant human growth hormone in
      children].

PMID- 24120060
TI  - [A case of vaginal bleeding in toddler and standardized diagnosis and treatment
      of the pediatric endocrine disorders].

PMID- 24120061
TI  - [Clinical significance of non-high-density lipoprotein cholesterol and its
      application in pediatrics].

PMID- 24120062
TI  - [Research advances in electrical status epilepticus in sleep].

PMID- 24120063
TI  - [Clinical and genetic characteristics of glucose transporter type 1 deficiency
      syndrome].
AB  - OBJECTIVE: To analyze the clinical and SLC2A1 gene mutation characteristics of
      glucose transporter type 1 deficiency syndrome. METHOD: The detailed clinical
      manifestations of six cases were recorded. The laboratory tests including EEG,
      MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations
      were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe
      amplification (MLPA). RESULT: Patient 1, 2 and 3 had classical clinical symptoms
      including infantile onset seizures, development delay. Patient 4, 5 and 6 had non
      classical clinical symptoms including paroxysmal behavior disturbance, weakness,
      ataxia, lethargy, especially after fasting or exercise, without severe seizures.
      The plasma glucose levels were normal. The CSF glucose levels decreased in all
      the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68
      mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to
      0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had
      focal and diffuse epileptiform discharge, and one of them also had paroxysmal
      occipital or generalized high-amplitude slow waves during awake and sleep time.
      MRI abnormalities were found in three patients, patient 1 with mild brain
      atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high
      signals in T2 in the frontal and occipital white matter, interpreted as
      hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has
      large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A
      (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively.
      Two patients were treated with ketogenic diet. The seizures disappeared and
      development became normal. Three patients responded to frequent meals with
      snacks. One patient refused any treatments, the symptoms continued to exist.
      CONCLUSION: The clinical manifestations of glucose transporter type 1 deficiency
      syndrome are varied. The common symptoms included infantile onset seizures and
      various paroxysmal events. These neurologic symptoms generally fluctuated and
      were influenced by factors such as fasting or fatigue. This feature could be a
      very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended
      in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a
      treatable neurometabolic disorder, early diagnosis and treatment may improve the
      prognosis of the patients.

PMID- 24120064
TI  - [Relationship between tic symptom severity and amplitude of low frequency
      fluctuation of resting-state functional magnetic resonance imaging of Tourette
      syndrome].
AB  - OBJECTIVE: To examine the relationship between tic symptom severity and amplitude
      of low frequency fluctuation (ALFF) brain functioning of the first-episode
      Tourette syndrome through resting-state functional magnetic resonance imaging
      (fMRI). METHOD: Sixteen subjects were all recruited from the outpatient
      department of pediatrics, Beijing Anding Hospital, Capital Medical University and
      were all first-episode Tourette syndrome patients [male: 13, female: 3; age: 6-16
      years; mean age: (11.00 +/- 2.92) years]; mean education time: (5.06 +/- 2.86)
      years; course: 14-104 months; mean (48.44 +/- 25.00) months; scores of YGTSS at
      baseline: tic severity score: 37.88 +/- 5.39; global damage score: 25.63 +/-
      12.63. All the subjects experienced resting-state fMRI scans and ALFF were
      calculated in three frequency ranges: 0.01-0.1 Hz, 0.01-0.027 Hz and 0.027-0.073
      Hz. First-episode Tourette syndrome patients and 16 gender, age, and education
      matched normal controls experienced resting-state fMRI scans. Correlation
      analysis was performed in between the amplitude of low frequency fluctuation
      (ALFF) and the severity of tic symptom. P < 0.05 and k value >= 10 were
      considered to be of significance. RESULT: In tic symptom patients, tic severity
      (total tic scores of YGTSS) was positively correlated with the ALFF values in the
      orbital part of left superior frontal gyrus (0.01-0.1 Hz:r = 0.83,0.027-0.073
      Hz:r = 0.91, P < 0.05, respectively), right middle frontal gyrus (0.01-0.027 Hz:r
      = 0.85,0.027-0.073 Hz:r = 0.57, P < 0.05, respectively ) and orbital part of left
      middle frontal gyrus (0.01-0.027 Hz:r = 0.64, P < 0.05). Tic severity was
      negatively correlated with the ALFF values in the right calcarine fissure and
      surrounding cortex (0.01-0.1 Hz:r = -0.65,0.01-0.027 Hz:r = -0.69, P < 0.05,
      respectively ) and the left calcarine fissure and surrounding cortex (0.027-0.073
      Hz:r = -0.81, P < 0.05). CONCLUSION: Tic symptom severity of the first-episode
      Tourette syndrome is associated with abnormal brain activity patterns of specific
      brain areas.

PMID- 24120065
TI  - [Human umbilical cord blood mononuclear cell transplantation promotes long-term
      neurobehavioral functional development of newborn SD rats with hypoxic ischemic
      brain injury].
AB  - OBJECTIVE: To explore the effect of human umbilical cord blood mononuclear cells
      (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal
      SD rat with hypoxic ischemic brain injury (HIBI). METHOD: A modified newborn rat
      model that had a combined hypoxic and ischemic brain injury as described by Rice
      Vannucci was used, early nervous reflex, the Morris water maze and walking track
      analysis were used to evaluate nervous behavioral function, and brain MRI, HE
      staining to evaluate brain damage recovery. RESULT: Newborn rat Rice-Vannucci
      model showed significant brain atrophy, obvious hemiplegia of contralateral
      limbs,e.g right step length [(7.67 +/- 0.46) cm vs. (8.22 +/- 0.50) cm, F =
      1.494] and toe distance [(0.93 +/- 0.06) cm vs. (1.12 +/- 0.55) cm, F = 0.186]
      were significantly reduced compared with left side, learning and memory ability
      was significantly impaired compared with normal control group (P < 0.01); Cliff
      aversion [(8.44 +/- 2.38) s vs.(14.22 +/- 5.07) s, t = 4.618] and negative
      geotaxis reflex time [(7.26 +/- 2.00) s vs. (11.76 +/- 3.73) s, t = 4.755] on
      postnatal 14 days of HIBI+ transplantation group were significantly reduced
      compared with HIBI+NaCl group (P < 0.01) ; the Morris water maze experiment
      showed escape latency [ (23.11 +/- 6.64) s vs. (34.04 +/- 12.95) s, t = 3.356]
      and swimming distance [ (9.12 +/- 1.21) cm vs.(12.70 +/- 1.53) cm, t = 17.095] of
      HIBI+transplantation group were significantly reduced compared with those of
      HIBI+NaCl group (P < 0.01) ; the residual brain volume on postnatal 10 d [ (75.37
      +/- 4.53)% vs. (67.17 +/- 4.08)%, t = -6.017] and 67 d [ (69.05 +/- 3.58)%
      vs.(60.83 +/- 3.69)%, t = -7.148]of HIBI+ transplantation group were
      significantly larger than those of HIBI+NaCl group (P < 0.01); After human UCBMC
      transplantation, left cortical edema significantly reduced and nerve cell
      necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl
      group. CONCLUSION: Human UCBMC intraperitoneal transplantation significantly
      promoted recovery of injured brain cells and neurobehavioral function
      development.

PMID- 24120066
TI  - [Evaluation of the efficacy of two successive protocols on pediatric acute
      lymphoblastic leukemia with E2A-PBX1 fusion gene].
AB  - OBJECTIVE: To evaluate the efficacy of BCH-03 and CCLG-08 protocols in treating
      E2A-PBX1 pediatric acute lymphoblastic leukemia (ALL). METHOD: From January 2003
      to January 2011, 59 ALL patients identified as E2A-PBX1 were analyzed in a
      retrospective study. There were 37 and 22 patients treated with Protocol BCH-03
      and CCLG-08, respectively. The clinical characteristics at diagnosis, response to
      early treatment, the time of relapse, relapse-free survival (RFS) and event-free
      survival (EFS) in the two groups were analyzed. RESULT: There were no significant
      differences in gender, age, initial white blood cell count, the central nervous
      system involvement, immunophenotype, prednisone response, the rate of complete
      remission, and the time of relapse between the two groups (P > 0.05). The only
      difference in induction therapy of the two protocols existed in the
      glucocorticoids used, that is, BCH-03 used 60 mg/m(2) prednisolone and CCLG-08
      used 6 mg/m(2) dexamethasone. The doses of vincristine, daunorubicin and L
      asparaginase were the same in the two groups. At the end of induction therapy,
      the MRD negativity rate in BCH-03 group was significantly higher than that in
      CCLG-08 group (84.2% vs. 47.1%, P = 0.018). The incidences of severe infection of
      the two groups during induction of remission were similar (P = 0.135). The EFS of
      BCH-03 group was significantly superior to that of CCLG-08 group (94.5% vs.
      71.5%, P = 0.010), and the RFS of BCH-03 group tended to be better than that of
      CCLG-08 group (94.5% vs. 78.6%, P = 0.059). CONCLUSION: Compared to Protocol CCLG
      08, Protocol BCH-03 was more effective for pediatric E2A-PBX1 ALL, and 60 mg/m(2)
      prednisolone was more suitable for the induction therapy of this subtype of
      pediatric ALL.

PMID- 24120067
TI  - [Expression and significance of interleukin-6, interferon-inducible protein-10
      and interleukin-17 in serum and synovial fluid of patients with juvenile
      idiopathic arthritis].
AB  - OBJECTIVE: To detect the disparity of three cytokines interleukin-6 (IL-6),
      interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral
      blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis
      (JIA). METHOD: Serum concentrations of the three cytokines were measured in 27
      patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28
      healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen
      patients with no marked arthritis symptom or only temporary arthralgia were
      enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were
      examined for cytokine levels. RESULT: (1) The statistically significant
      difference in serum IL-6 was detected between sJIA and healthy control group
      [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant
      difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L
      vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically
      significant differences between sJIA group and healthy control group in serum
      concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05],
      yet compared to healthy control group, no significant difference in concentration
      level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2)
      ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly
      higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4
      111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01,
      respectively], but there was only significant difference in IL-17 between pJIA SF
      and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01]. CONCLUSION:
      IL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may
      be the biomarker associated with arthritis in early JIA stage. Both
      autoinflammation and autoimmune response may be involved in the pathogenesis of
      sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB
      may not be significantly increased. The prominent expression gradient between SF
      and PB of IP-10 maybe the basis of performing chemotaxis and further causing
      joint damage.

PMID- 24120068
TI  - [A case of Guillain-Barre syndrome complicated with posterior reversible
      encephalopathy syndrome].

PMID- 24120069
TI  - [Summary of the 15(th) National Congress of Pediatric Nephrology].

PMID- 24120070
TI  - A technique to remove a fractured acrylic resin pattern from the post space.

PMID- 24120071
TI  - Marginal adaptation of ceramic crowns: a systematic review.
AB  - STATEMENT OF PROBLEM: After the development of a variety of ceramic restorative
      systems over the past 20 years, the fabrication of fixed dental prostheses has
      undergone considerable change. Esthetics and resistance to fracture are two of
      the main determinants of the success of a restoration; the third is marginal
      adaptation. Therefore, a systematic review of the literature dedicated to the
      marginal accuracy of ceramic systems is indicated. PURPOSE: This study reviewed
      the current scientific literature that pertains to the marginal fit of ceramic
      crowns fabricated with different systems and investigated the factors that
      influence marginal adaptation. MATERIAL AND METHODS: An electronic search was
      completed by using the PubMed and Scopus databases with the following combination
      of key words: (discrepancy or fit or gaps or adaptation) and (disilicate or
      ceramic) and (copings or crowns). The search was limited to English-language peer
      reviewed articles published before April 15, 2012. Titles and abstracts were read
      to identify articles that fulfilled the inclusion criteria designed for this
      review. RESULTS: Of 469 studies identified, 54 satisfied the selection criteria
      and were included in this review. All were published between 1994 and 2012. A
      total of 17 ceramic systems were tested in 48 in vitro and 6 in vivo studies. Of
      all the marginal gaps measured, 94.9% were in the range of clinical
      acceptability. Study heterogeneity made it impossible to conduct a proper meta
      analysis of research findings and to compare and rank the various systems in
      terms of marginal fit. Four parameters were found to influence marginal
      adaptation: finish line configuration, value of the predefined cementing space,
      veneering process, and cementation. CONCLUSIONS: The systems evaluated in the
      selected articles generally provide a clinically acceptable marginal fit. The
      current state of research does not allow for a proper comparison of the various
      systems in terms of marginal fit. The use of computer x-ray microtomography is
      recommended for further research on marginal adaptation.

PMID- 24120072
TI  - Analysis of four dental alloys following torch/centrifugal and induction/ vacuum
      pressure casting procedures.
AB  - STATEMENT OF PROBLEM: Previous studies have shown casting methodology to
      influence the as-cast properties of dental casting alloys. It is important to
      consider clinically important mechanical properties so that the influence of
      casting can be clarified. PURPOSE: The purpose of this study was to evaluate how
      torch/centrifugal and inductively cast and vacuum-pressure casting machines may
      affect the castability, microhardness, chemical composition, and microstructure
      of 2 high noble, 1 noble, and 1 base metal dental casting alloys. MATERIAL AND
      METHODS: Two commonly used methods for casting were selected for comparison:
      torch/centrifugal casting and inductively heated/ vacuum-pressure casting. One
      hundred and twenty castability patterns were fabricated and divided into 8
      groups. Four groups were torch/centrifugally cast in Olympia (O), Jelenko O (JO),
      Genesis II (G), and Liberty (L) alloys. Similarly, 4 groups were cast in O, JO,
      G, and L by an inductively induction/vacuum-pressure casting machine. Each
      specimen was evaluated for casting completeness to determine a castability value,
      while porosity was determined by standard x-ray techniques. Each group was
      metallographically prepared for further evaluation that included chemical
      composition, Vickers microhardness, and grain analysis of microstructure. Two-way
      ANOVA was used to determine significant differences among the main effects.
      Statistically significant effects were examined further with the Tukey HSD
      procedure for multiple comparisons. Data obtained from the castability
      experiments were non-normal and the variances were unequal. They were analyzed
      statistically with the Kruskal-Wallis rank sum test. Significant results were
      further investigated statistically with the Steel-Dwass method for multiple
      comparisons (alpha=.05). RESULTS: The alloy type had a significant effect on
      surface microhardness (P<.001). In contrast, the technique used for casting did
      not affect the microhardness of the test specimen (P=.465). Similarly, the
      interaction between the alloy and casting technique was not significant (P=.119).
      A high level of castability (98.5% on average) was achieved overall. The
      frequency of casting failures as a function of alloy type and casting method was
      determined. Failure was defined as a castability index score of <100%. Three of
      28 possible comparisons between alloy and casting combinations were statistically
      significant. The results suggested that casting technique affects the castability
      index of alloys. Radiographic analysis detected large porosities in regions near
      the edge of the castability pattern and infrequently adjacent to noncast
      segments. All castings acquired traces of elements found in the casting
      crucibles. The grain size for each dental casting alloy was generally finer for
      specimens produced by the induction/vacuum-pressure method. The difference was
      substantial for JO and L. CONCLUSIONS: This study demonstrated a relation between
      casting techniques and some physical properties of metal ceramic casting alloys.

PMID- 24120073
TI  - International travel by persons with medical comorbidities: understanding risks
      and providing advice.
AB  - OBJECTIVE: To describe the medical conditions, travel plans, counseling, and
      medications prescribed for high-risk international travelers. PATIENTS AND
      METHODS: This cross-sectional study was conducted from March 1, 2008, through
      July 31, 2010, in 5 clinics in the greater Boston area. We assessed all travelers
      seen for pretravel care and compared demographic characteristics, travel plans,
      pretravel counseling, and interventions for healthy and high-risk travelers (as
      defined by medical history or pregnancy). RESULTS: Of 15,440 travelers, 2769
      (17.9%) were high-risk; 644 of 2769 (23.3%) were immunocompromised travelers,
      2056 (74.3%) had medical comorbidities, and 69 (2.5%) were pregnant women. The
      median age of high-risk travelers was 47 years compared with 32 years for healthy
      travelers (P=.0001). High-risk travelers visited the clinic a median of 25 days
      (range, 10-44 days) before departure. Overall, 2562 (93.9%) of high-risk
      travelers visited countries with medium or high risk of typhoid fever, 2340
      (85.7%) visited malaria-risk countries, and 624 (22.8%) visited yellow fever
      endemic countries. Of travelers to yellow fever-endemic countries, 8 of 23
      (34.8%) pregnant women and 64 of 144 (44.4%) immunocompromised travelers received
      yellow fever vaccine. Of eligible high-risk travelers, 11 of 76 (14.5%) received
      a pneumococcal vaccine, 213 of 640 (33.3%) influenza vaccine, and 956 of 2681
      (35.7%) either tetanus-diphtheria or tetanus-diphtheria-pertussis vaccine.
      CONCLUSION: High-risk travelers made up nearly 20% of patients in these travel
      clinics, and they mostly traveled to destinations with malaria and typhoid risk.
      For health care professionals caring for travelers with underlying medical
      problems, providing appropriate travel counseling and making vaccine decisions,
      such as for yellow fever, are complex. Travelers with complicated medical
      histories may warrant evaluation by an experienced travel medicine specialist.

PMID- 24120075
TI  - Leadership in complex networks: the importance of network position and strategic
      action in a translational cancer research network.
AB  - BACKGROUND: Leadership behaviour in complex networks is under-researched, and
      little has been written concerning leadership of translational research networks
      (TRNs) that take discoveries made 'at the bench' and translate them into
      practices used 'at the bedside.' Understanding leaders' opportunities and
      behaviours within TRNs working to solve this key problem in implementing evidence
      into clinical practice is therefore important. This study explored the network
      position of governing body members and perceptions of their role in a new TRN in
      Sydney, Australia. The paper asks three questions: Firstly, do the formal,
      mandated leaders of this TRN hold key positions of centrality or brokerage in the
      informal social network of collaborative ties? Secondly, if so, do they recognise
      the leadership opportunities that their network positions afford them? Thirdly,
      what activities associated with these key roles do they believe will maximise the
      TRN's success? METHODS: Semi-structured interviews of all 14 governing body
      members conducted in early 2012 explored perceptions of their roles and sought
      comments on a list of activities drawn from review of successful
      transdisciplinary collaboratives combined with central and brokerage roles. An on
      line, whole network survey of all 68 TRN members sought to understand and map
      existing collaborative connections. Leaders' positions in the network were
      assessed using UCInet, and graphs were generated in NetDraw. RESULTS: Social
      network analysis identified that governing body members had high centrality and
      high brokerage potential in the informal network of work-related ties. Interviews
      showed perceived challenges including 'silos' and the mismatch between academic
      and clinical goals of research. Governing body members recognised their central
      positions, which would facilitate the leadership roles of leading, making
      decisions, and providing expert advice necessary for the co-ordination of effort
      and relevant input across domains. Brokerage potential was recognised in their
      clearly understood role of representing a specialty, campus or research group on
      the governing body to provide strategic linkages. Facilitation, mentoring and
      resolving conflicts within more localised project teams were spoken of as
      something 'we do all the time anyway,' as well as something they would do if
      called upon. These leadership roles are all linked with successful collaborative
      endeavours in other fields. CONCLUSIONS: This paper links the empirical findings
      of the social network analysis with the qualitative findings of the interviews to
      show that the leaders' perceptions of their roles accord with both the potential
      inherent in their network positions as well as actual activities known to
      increase the success of transdisciplinary teams. Understanding this is key to
      successful TRNs.

PMID- 24120074
TI  - Parental separation and early substance involvement: results from children of
      alcoholic and cannabis dependent twins.
AB  - BACKGROUND: Risks associated with parental separation have received limited
      attention in research on children of parents with substance use disorders. We
      examined early substance involvement as a function of parental separation during
      childhood and parental alcohol and cannabis dependence. METHOD: Data were drawn
      from 1318 adolescent offspring of monozygotic (MZ) or dizygotic (DZ) Australian
      twin parents. Cox proportional hazards regression analyses were conducted
      predicting age at first use of alcohol, first alcohol intoxication, first use and
      first regular use of cigarettes, and first use of cannabis, from parental
      separation and both parent and cotwin substance dependence. Parent and cotwin
      alcohol and cannabis dependence were initially modeled separately, with post hoc
      tests for equality of effects. RESULTS: With few exceptions, risks associated
      with parental alcohol versus cannabis dependence could be equated, with results
      largely suggestive of genetic transmission of risk from parental substance
      (alcohol or cannabis) dependence broadly defined. Controlling for parental
      substance dependence, parental separation was a strong predictor for all
      substance use variables, especially through age 13. CONCLUSION: Together,
      findings underscore the importance of parental separation as a risk-factor for
      early substance involvement over and above both genetic and environmental
      influences specific to parental alcohol and cannabis dependence.

PMID- 24120076
TI  - Urinary CC16 after challenge with dry air hyperpnoea and mannitol in recreational
      summer athletes.
AB  - Airway epithelial injury is regarded as a key contributing factor to the
      pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. The
      concentration of the pneumoprotein club cell (Clara cell) CC16 in urine has been
      found to be a non-invasive marker for hyperpnoea-induced airway epithelial
      perturbation. Exercise-hyperpnoea induces mechanical, thermal and osmotic stress
      to the airways. We investigated whether osmotic stress alone causes airway
      epithelial perturbation in athletes with suspected EIB. Twenty-four recreational
      summer sports athletes who reported respiratory symptoms on exertion performed a
      standard eucapnic voluntary hyperpnoea test with dry air and a mannitol test
      (osmotic challenge) on separate days. Median urinary CC16 increased from 120 to
      310 rhog MUmol creatinine(-1) after dry air hyperpnoea (P = 0.002) and from 90 to
      191 rhog MUmol creatinine(-1) after mannitol (P = 0.021). There was no difference
      in urinary CC16 concentration between athletes who did or did not
      bronchoconstrict after dry air hyperpnoea or mannitol. We conclude that, in
      recreational summer sports athletes with respiratory symptoms, osmotic stress per
      se to the airway epithelium induces a rise in urinary excretion of CC16. This
      suggests that hyperosmolarity of the airway surface lining perturbs the airway
      epithelium in symptomatic athletes.

PMID- 24120077
TI  - That chorioamnionitis is a risk factor for bronchopulmonary dysplasia--the case
      against.
AB  - Bronchopulmonary dysplasia (BPD) is the most frequent long term sequelae in
      infants born at less than 29 weeks of gestational age (GA) and histological
      chorioamnionitis (CA) is the most frequent condition associated with very preterm
      birth. Numerous studies have explored the association between BPD and CA with
      conflicting results. This inconsistency may be attributable to differences in
      populations, definitions, methods, and whether potential confounding factors such
      as GA, antenatal steroids, and post natal events were considered. A recent
      systematic review and meta-analysis shows some evidence of an association between
      BPD and CA; however, results adjusting for important confounders show more
      conservative measures of association. In addition, there was evidence of
      publication bias: when controlling for publication bias the results were more
      conservative and adjusted results were no longer significant. Recent large cohort
      studies not included in the systematic review do not support the belief that CA
      is associated with an increased risk of BPD. Despite a large body of evidence, CA
      cannot be definitively considered a risk factor for BPD. 

PMID- 24120078
TI  - [Effect of modal computer-based alerts on the prescription of valproic acid and
      meropenem].
AB  - OBJECTIVE: To analyze the effect of modal computer-based alerts on the
      concomitant prescription of valproic acid (VPA) and meropenem. MATERIAL AND
      METHOD: Analytical intervention study conducted in a tertiary hospital for eleven
      months. Hospitalized patients with a diagnosis of epilepsy and treated with VPA
      and meropenem in concomitant therapy were included. In the computerized
      prescription order entry software an automatic non-modal alert was reconverted to
      a modal one. This was triggered when the physician introduced VPA and meropenem
      together in the same prescription. To measure the effect of this alert the
      prescription habits were compared with a previous period in which the alert was
      not modal. RESULTS: Modal computer-based alert modified the prescription habit by
      reducing the number of patients with concomitant treatment from 13 to 4 (P=.046).
      However, it was notable that the number of requests for VPA serum levels
      decreased, and the average number of concomitant days of treatment rose from 4.7
      to 8.75 in those patients in which none of the drugs was suspended. CONCLUSIONS:
      The implementation of modal computer-based alerts reduces patient exposure to
      concomitant treatment with meropenem and VPA.

PMID- 24120079
TI  - [Consensus conference on providing information of adverse events to patients and
      relatives].
AB  - OBJECTIVE: To develop recommendations regarding "Information about adverse events
      to patients and their families", through the implementation of a consensus
      conference. MATERIAL AND METHODS: A literature review was conducted to identify
      all relevant articles, the major policies and international guidelines, and the
      specific legislation developed in some countries on this process. The literature
      review was the basis for responding to a series of questions posed in a public
      session. A group of experts presented the best available evidence, interacting
      with stakeholders. At the end of the session, an interdisciplinary and multi
      professional jury established the final recommendations of the consensus
      conference. RESULTS: The main recommendations advocate the need to develop
      policies and institutional guidelines in our field, favouring the patient adverse
      events disclosure process. The recommendations emphasize the need for the
      training of professionals in communication skills and patient safety, as well as
      the development of strategies for supporting professionals who are involved in an
      adverse event. The assessment of the interest and impact of specific legislation
      that would help the implementation of these policies was also considered.
      CONCLUSIONS: A cultural change is needed at all levels, nuanced and adapted to
      the specific social and cultural aspects of our social and health spheres, and
      involves all stakeholders in the system to create a framework of trust and
      credibility in which the processing of information about adverse events may
      become effective.

PMID- 24120080
TI  - Cross-talk between mineralocorticoid receptor/angiotensin II type 1 receptor and
      mitogen-activated protein kinase pathways underlies aldosterone-induced atrial
      fibrotic responses in HL-1 cardiomyocytes.
AB  - BACKGROUND: Aldosterone is increasingly recognized for its involvement in atrial
      structural remodeling. However, the precise molecular mechanisms and signal
      pathways underlying aldosterone-induced atrial fibrosis are unknown. METHODS:
      Western blotting was used to investigate the effects of aldosterone on the
      expression of mineralocorticoid receptor (MR), angiotensin II type I receptor
      (AT1), mitogen-activated protein kinases (MAPKs), and fibrotic marker proteins in
      cultured HL-1 cardiomyocytes. RESULTS: Aldosterone upregulated MR and AT1
      expressions in a concentration-dependent and time-dependent manner. Aldosterone
      (10(-6)M) significantly and time-dependently increased activation of the
      extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase
      (JNK), p38MAPK pathways, and the protein expression of collagen 1A and 3A (COL1A
      and COL3A), transforming growth factor (TGF)-beta1, and alpha-smooth muscle actin
      (SMA). Pre-treatment with eplerenone (10(-10)M) prevented the increased
      expression of MR, MAPK signals and the above profibrotic molecules, but amplified
      the increase in AT1 level stimulated by aldosterone (10(-6)M). Pre-treatment with
      losartan (10(-10)M) or MAPK pathway inhibitors (U0126 or SP600125) abolished
      aldosterone-induced MR upregulation and significantly inhibited the expression of
      the above fibrotic marker proteins, indicating the critical role of MR and the
      requirement for active AT1 in the development of aldosterone-induced atrial
      fibrosis. CONCLUSIONS: Elevated MR activity plays a central role in aldosterone
      mediated activation of the MAPK signaling pathway and subsequent profibrotic
      effects in HL-1 atrial cells. MR/AT1 and the MAPK signaling pathway interact to
      trigger the molecular mechanism underlying the aldosterone-induced atrial
      fibrotic response. Our results support the view that MR blockade in conjunction
      with AT1 blockade can prevent the occurrence of atrial fibrillation.

PMID- 24120081
TI  - Comments on 'Human-climate interaction during the early Upper Paleolithic:
      testing the hypothesis of an adaptive shift between the Proto-Aurignacian and the
      Early Aurignacian' by Banks et al.

PMID- 24120082
TI  - Polymorphisms of metal transporter genes DMT1 and ATP7A in Wilson's disease.
AB  - Wilson's disease (WND) is an inherited disorder of copper metabolism. Divalent
      metal transporter1 (DMT1) and ATP7A play important roles in metal transport in
      humans. The frequency of two single nucleotide polymorphisms of the DMT1 gene:
      DMT1 IVS4 C>A, DMT1 11245 T>C and two of the ATP7A gene: rs1062472 T>C, ATP7A rs
      2227291 G>C have been evaluated in a population of 108 Wilson's disease patients
      and 108 sex- and age-matched healthy volunteers. The DMT1 IVS4 C(+) allele
      occurred more frequently in WND than in the healthy controls. The allele
      frequencies of other studied polymorphisms in WND group were in line with
      frequencies obtained for healthy volunteers. Neither of the polymorphisms had an
      impact on the age at onset or clinical phenotype of WND. 

PMID- 24120083
TI  - Water vapour is a pre-oviposition attractant for the malaria vector Anopheles
      gambiae sensu stricto.
AB  - BACKGROUND: To date no semiochemicals affecting the pre-oviposition behaviour of
      the malaria vector Anopheles gambiae sensu lato have been described. Water vapour
      must be the major chemical signal emanating from a potential larval habitat, and
      although one might expect that gravid An. gambiae s.l. detect and respond to
      water vapour in their search for an aquatic habitat, this has never been
      experimentally confirmed for this species. This study aimed to investigate the
      role of relative humidity or water vapour as a general cue for inducing gravid
      An. gambiae sensu stricto to make orientated movements towards the source.
      METHODS: Three experiments were carried out with insectary-reared An. gambiae
      s.s. One with unfed females and two with gravid females during their peak
      oviposition time in the early evening. First, unfed females and gravid females
      were tested separately in still air where a humidity difference was established
      between opposite ends of a WHO bioassay tube and mosquitoes released individually
      in the centre of the tube. Movement of mosquitoes to either low or high humidity
      was recorded. Additionally, gravid mosquitoes were released into a larger air
      flow olfactometer and responses measured towards collection chambers that
      contained cups filled with water or empty cups. RESULTS: Unfed females equally
      dispersed in the small bioassay tubes to areas of high and low humidity (mean 50%
      (95% confidence interval (CI) 38-62%). In contrast, gravid females were 2.4 times
      (95% CI 1.3-4.7) more likely to move towards high humidity than unfed females.
      The results were even more pronounced in the airflow olfactometer. Gravid females
      were 10.6 times (95% CI 5.4-20.8) more likely to enter the chamber with water
      than a dry chamber. CONCLUSIONS: Water vapour is a strong pre-oviposition
      attractant to gravid An. gambiae s.s. in still and moving air and is likely to be
      a general cue used by mosquitoes for locating aquatic habitats.

PMID- 24120084
TI  - Zonal NePhRO scoring system: a superior renal tumor complexity classification
      model.
AB  - BACKGROUND: Since the advent of the first standardized renal tumor complexity
      system, many subsequent scoring systems have been introduced, many of which are
      complicated and can make it difficult to accurately measure data end points. In
      light of these limitations, we introduce the new zonal NePhRO scoring system.
      PATIENTS AND METHODS: The zonal NePhRO score is based on 4 anatomical components
      that are assigned a score of 1, 2, or 3, and their sum is used to classify renal
      tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to
      collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of
      the tumor, and (O)rganization of the tumor. In this retrospective study, we
      evaluated patients exhibiting clinical stage T1a or T1b who underwent open
      partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was
      assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic
      properties, nearness of tumor to the collecting system or sinus in millimeters,
      anterior/posterior, location relative to polar lines) score, and a blinded
      reviewer used the same preoperative imaging study to obtain both scores.
      Additional data points gathered included age, clamp time, complication rate,
      urine leak rate, intraoperative blood loss, and pathologic tumor size. RESULTS:
      One hundred sixty-six patients underwent open partial nephrectomy. There were 37
      perioperative complications quantitated using the validated Clavien-Dindo system;
      their occurrence was predicted by the NePhRO score on both univariate and
      multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and
      tumor diameter were all correlated with the zonal NePhRO score on univariate
      analysis only. CONCLUSION: The zonal NePhRO scoring system is a simpler tool that
      accurately predicts the surgical complexity of a renal lesion.

PMID- 24120085
TI  - The plasminogen activator system: involvement in central nervous system
      inflammation and a potential site for therapeutic intervention.
AB  - BACKGROUND: Extracellular proteases such as plasminogen activators (PAs) and
      matrix metalloproteinases modulate cell-cell and cell-matrix interactions.
      Components of the PA/plasmin system have been shown to be increased in areas of
      inflammation, and have been suggested to play a role in inflammatory neurologic
      disorders such as epilepsy, stroke, brain trauma, Alzheimer's' disease and
      multiple sclerosis (MS). In the present study, we evaluated the involvement of
      the PA system in the animal model of MS, experimental autoimmune
      encephalomyelitis (EAE). METHODS: EAE was induced by myelin oligodendrocyte
      glycoprotein (MOG) in mice deficient for the urokinase PA (uPA-/-), or the
      urokinase PA receptor (uPAR-/-). Mice were evaluated for EAE clinical signs and
      histopathologic parameters, and compared with wild-type (WT) EAE mice.
      Lymphocytes from the knockout (KO) and WT mice were analyzed for ex vivo
      restimulation, cytokine secretion, and antigen presentation. Finally, WT EAE mice
      were treated with PAI-1dp, an 18 amino acid peptide derived from the PA inhibitor
      protein (PAI-1). RESULTS: EAE was aggravated in uPA-/- and uPAR-/- mice, and this
      was accompanied by more severe histopathologic features and microglial
      activation. By contrast, specific T- cell reactivity towards the encephalitogenic
      antigen MOG was markedly reduced in the KO animals, as shown by a marked
      reduction in proliferation and pro-inflammatory cytokine secretion in these mice.
      Antigen presentation was also reduced in all the KO animals, raising an
      immunologic paradox. When the mice were treated with PAI-1, a peptide derived
      from the PA system, a marked and significant improvement in EAE was seen. The
      clinical improvement was linked to reduced T-cell reactivity, further emphasizing
      the importance of the PA system in immunomodulation during neuroinflammation.
      CONCLUSIONS: Cumulatively, our results suggest a role for uPA and uPAR in EAE
      pathogenesis, as exacerbation of disease was seen in their absence. Furthermore,
      the successful amelioration of EAE by PAI-1 treatment suggests that the PA system
      can be considered a potential site for therapeutic intervention in the treatment
      of neuroimmune diseases.

PMID- 24120086
TI  - Emotional reasoning and anxiety sensitivity: associations with social anxiety
      disorder in childhood.
AB  - BACKGROUND: Two specific cognitive constructs that have been implicated in the
      development and maintenance of anxiety symptoms are anxiety sensitivity and
      emotional reasoning, both of which relate to the experience and meaning of
      physical symptoms of arousal or anxiety. The interpretation of physical symptoms
      has been particularly implicated in theories of social anxiety disorder, where
      internal physical symptoms are hypothesized to influence the individual's
      appraisals of the self as a social object. METHOD: The current study compared 75
      children on measures of anxiety sensitivity and emotional reasoning: 25 with
      social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious
      children (aged 7-12 years). RESULTS: Children with social anxiety disorder
      reported higher levels of anxiety sensitivity and were more likely than both
      other groups to view ambiguous situations as anxiety provoking, whether physical
      information was present or not. There were no group differences in the extent to
      which physical information altered children's interpretation of hypothetical
      scenarios. LIMITATIONS: This study is the first to investigate emotional
      reasoning in clinically anxious children and therefore replication is needed. In
      addition, those in both anxious groups commonly had comorbid conditions and,
      consequently, specific conclusions about social anxiety disorder need to be
      treated with caution. CONCLUSION: The findings highlight cognitive
      characteristics that may be particularly pertinent in the context of social
      anxiety disorder in childhood and which may be potential targets for treatment.
      Furthermore, the findings suggest that strategies to modify these particular
      cognitive constructs may not be necessary in treatments of some other childhood
      anxiety disorders.

PMID- 24120087
TI  - Amplitude of low-frequency fluctuations in bipolar disorder: a resting state fMRI
      study.
AB  - OBJECTIVES: The spontaneous low frequency fluctuations (LFF) of blood oxygenation
      level-dependent (BOLD) signal in resting state have been identified as a
      biological measure of baseline spontaneous activity in the brain. Increasingly,
      studies of spontaneous resting state functional connectivity have demonstrated
      neural network abnormalities in bipolar disorder (BD). This study used the
      amplitude of low frequency fluctuations (ALFF) to explore the regional functional
      changes in BD during resting state. METHODS: Twenty-nine BD participants and 29
      matched healthy controls (HC) were recruited to undergo resting-state functional
      magnetic resonance imaging scan on a 3.0T magnetic resonance imaging system. The
      ALFF of BOLD signal in gray matter for each participant was calculated, and then
      was compared between BD and HC using ALFF maps. RESULTS: Compared to the HC
      group, the BD group showed increased ALFF in ventral prefrontal cortex, dorsal
      lateral prefrontal cortex, frontal eye field, insula, and putamen with extension
      into the ventral striatum, as well as decreased ALFF in the lingual gyrus
      (p<0.05, corrected). LIMITATIONS: Although we observed differences in ALFF
      between BD and HC, we cannot conclusively state that these differences are caused
      by the pathophysiology of BD since most of BD participants were being treated
      with medications at the time of scanning. CONCLUSIONS: Our results revealed
      altered regional brain activity in BD during resting state. The affected regions
      have been associated with BD pathophysiology. This suggests that methods using
      ALFF method may potentially be useful in further studies of this disorder.

PMID- 24120089
TI  - Soluble urokinase-type plasminogen activator receptor as a prognostic biomarker
      in critically ill patients.
AB  - PURPOSE: The aim of this study was to assess the role of blood soluble urokinase
      type plasminogen activator receptor (suPAR) levels in the diagnosis and
      prognostication of sepsis in critically ill patients. METHODS: Serum suPAR levels
      were measured prospectively in adult intensive care unit (ICU) patients on
      admission and then daily until ICU discharge (maximum of 14 days) using an enzyme
      linked immunosorbent assay kit. Normal levels were established in 31 healthy
      controls. RESULTS: We included 258 patients (161 men); median admission Acute
      Physiology and Chronic Health Evaluation II and Sequential Organ Failure
      Assessment scores were 17 (9-23) and 6 (3-9), respectively. The mortality rate
      was 13.6%. Sepsis was diagnosed on admission in 94 patients (36%), of whom 23 had
      severe sepsis and 49 had septic shock. On admission, septic patients had higher
      suPAR levels than did nonseptic patients (8.9 [5.9-12.7] vs 3.7 [2.7-5.4] ng/mL),
      but the predictive value of suPAR for diagnosing sepsis was weaker than that of C
      reactive protein. During the week after ICU admission, serum suPAR concentrations
      correlated with Sequential Organ Failure Assessment scores over time. High suPAR
      levels on admission were a strong independent predictor for ICU and 28-day
      mortality. In the global population, a suPAR level higher than 6.15 ng/mL had 66%
      sensitivity and 64% specificity for prediction of ICU mortality, with a receiver
      operating characteristic area under the curve of 0.726 (95% confidence interval,
      0.645-0.808). CONCLUSIONS: In ICU patients, serum suPAR concentrations have
      limited use for identifying sepsis, but their time course correlated with the
      degree of organ dysfunction, and they have prognostic value in septic and
      nonseptic populations.

PMID- 24120088
TI  - 5,6-Dihydro-5-aza-2'-deoxycytidine potentiates the anti-HIV-1 activity of
      ribonucleotide reductase inhibitors.
AB  - The nucleoside analog 5,6-dihydro-5-aza-2'-deoxycytidine (KP-1212) has been
      investigated as a first-in-class lethal mutagen of human immunodeficiency virus
      type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase
      II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs)
      combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the
      activity of gemcitabine and resveratrol and simultaneously increased the viral
      mutant frequency. G-to-C mutations predominated with the KP-1212-resveratrol
      combination. These observations represent the first demonstration of a mild anti
      HIV-1 mutagen potentiating the antiretroviral activity of RNRIs and encourage the
      clinical translation of enhanced viral mutagenesis in treating HIV-1 infection. 

PMID- 24120090
TI  - Prediction of delirium in critically ill patients with elevated C-reactive
      protein.
AB  - BACKGROUND AND PURPOSE: Delirium is thought to be associated with systemic
      inflammatory response. However, its association with the most widely used
      inflammatory biomarker C-reactive protein (CRP) has not been well established. We
      aimed to examine whether CRP on intensive care unit (ICU) entry was associated
      with subsequent development of delirium. DESIGN AND SETTING: This prospective
      observational study was conducted in a mixed 24-bed ICU in a tertiary teaching
      hospital. METHODS: All patients admitted to the ICU from February 2011 to June
      2012 were screened for eligibility. Demographic data and clinical characteristics
      of included patients were recorded. Patients were screened for the presence of
      delirium by using the tool Confusion Assessment Method for the ICU (CAM-ICU). C
      reactive protein was obtained on ICU entry and 24 hours thereafter. Eligible
      patients were followed up for 28 days or until death. Univariate and multivariate
      analyses were performed to evaluate independent risk factors for delirium.
      Clinical outcome included the length of stay (LOS) in the ICU, 28-day mortality,
      and duration of mechanical ventilation. Two-tailed P < .05 was considered
      statistically significant. RESULTS: A total of 223 patients were included during
      study period. In univariate analysis, patients with delirium showed significantly
      higher CRP values than those without (120.5 vs 57.5 mg/L; P = .0001). By
      adjusting for confounding variables (including age, sex, Acute Physiology and
      Chronic Health Evaluation II, intubation, living alone, physical restraint,
      alcohol drinking, smoking, type of medical condition, and hospital LOS before ICU
      admission) in logistic regression model, CRP remained an independent predictor of
      delirium (odds ratio, 1.07; 95% confidence interval, 1.01-1.15). As compared with
      nondelirious patients, those with delirium showed longer LOS in ICU (13 vs 5
      days; P < .001) and duration of mechanical ventilation (6 vs 1 days; P < .001).
      An increase in CRP greater than 8.1 mg/L within 24 hours was associated with 4
      fold increase in the risk of delirium (odds ratio: 4.47, 95% confidence interval,
      1.28-15.60). CONCLUSION: C-reactive protein measured on ICU entry and its changes
      within 24 hours are risk indicators of delirium. Further studies exploring the
      treatment of delirium according to CRP levels are warranted.

PMID- 24120091
TI  - Racial differences in withdrawal of mechanical ventilation do not alter mortality
      in neurologically injured patients.
AB  - PURPOSE: Racial differences in withdrawal of mechanical ventilation (WMV) have
      been demonstrated among patients with severe neurologic injuries. We ascertained
      whether such differences might be accounted for by imbalances in socioeconomic
      status or disease severity, and whether such racial differences impact hospital
      mortality or result in greater discharge to long-term care facilities. MATERIALS
      AND METHODS: We evaluated WMV among 1885 mechanically ventilated patients with
      severe neurologic injury (defined as Glasgow Coma Scale <9), excluding those
      progressing to brain death within the first 48 hours. RESULTS: Withdrawal of
      mechanical ventilation was less likely in nonwhite patients (22% vs 31%, P <
      .001). Nonwhites were younger and were more likely to have Medicaid or no
      insurance, live in ZIP codes with low median household incomes, be unmarried, and
      have greater illness severity; but after adjustment for these variables, racial
      difference in WMV persisted (odds ratio, 0.56; 95% confidence interval, 0.42
      0.76). Nonwhite patients were more likely to die instead with full support or
      progress to brain death, resulting in equivalent overall hospital mortality (40%
      vs 42%, P = .44). Among survivors, nonwhites were more likely to be discharged to
      long-term care facilities (27% vs 17%, P < .001). CONCLUSIONS: Surrogates of
      nonwhite neurologically injured patients chose WMV less often even after
      correcting for socioeconomic status and other confounders. This difference in end
      of-life decision making does not appear to alter hospital mortality but may
      result in more survivors left in a disabled state.

PMID- 24120092
TI  - Differential oscillatory electroencephalogram between attention
      deficit/hyperactivity disorder subtypes and typically developing adolescents.
AB  - BACKGROUND: A neurobiological-based classification of attention
      deficit/hyperactivity disorder (ADHD) subtypes has thus far remained elusive. The
      aim of this study was to use oscillatory changes in the electroencephalogram
      (EEG) related to informative cue processing, motor preparation, and top-down
      control to investigate neurophysiological differences between typically
      developing (TD) adolescents, and those diagnosed with predominantly inattentive
      (IA) or combined (CB) (associated with symptoms of inattention as well as
      impulsivity/hyperactivity) subtypes of ADHD. METHODS: The EEG was recorded from
      57 rigorously screened adolescents (12 to 17 years of age; 23 TD, 17 IA, and 17
      CB), while they performed a cued flanker task. We examined the oscillatory
      changes in theta (3-5 Hz), alpha (8-12 Hz), and beta (22-25 Hz) EEG bands after
      cues that informed participants with which hand they would subsequently be
      required to respond. RESULTS: Relative to TD adolescents, the IA group showed
      significantly less postcue alpha suppression, suggesting diminished processing of
      the cue in the visual cortex, whereas the CB group showed significantly less beta
      suppression at the electrode contralateral to the cued response hand, suggesting
      poor motor planning. Finally, both ADHD subtypes showed weak functional
      connectivity between frontal theta and posterior alpha, suggesting common top
      down control impairment. CONCLUSIONS: We found both distinct and common task
      related neurophysiological impairments in ADHD subtypes. Our results suggest that
      task-induced changes in EEG oscillations provide an objective measure, which in
      conjunction with other sources of information might help distinguish between ADHD
      subtypes and therefore aid in diagnoses and evaluation of treatment.

PMID- 24120093
TI  - Variation in serotonin transporter expression modulates fear-evoked hemodynamic
      responses and theta-frequency neuronal oscillations in the amygdala.
AB  - BACKGROUND: Gene association studies detect an influence of natural variation in
      the 5-hydroxytryptamine transporter (5-HTT) gene on multiple aspects of
      individuality in brain function, ranging from personality traits through to
      susceptibility to psychiatric disorders such as anxiety and depression. The
      neural substrates of these associations are unknown. Human neuroimaging studies
      suggest modulation of the amygdala by 5-HTT variation, but this hypothesis is
      controversial and unresolved, and difficult to investigate further in humans.
      METHODS: We used a mouse model in which the 5-HTT is overexpressed throughout the
      brain and recorded hemodynamic responses (using a novel in vivo voltammetric
      monitoring method, analogous to blood oxygen level-dependent functional magnetic
      resonance imaging) and local field potentials during Pavlovian fear conditioning.
      RESULTS: Increased 5-HTT expression impaired, but did not prevent, fear learning
      and significantly reduced amygdala hemodynamic responses to aversive cues.
      Increased 5-HTT expression was also associated with reduced theta oscillations,
      which were a feature of aversive cue presentation in controls. Moreover, in
      control mice, but not those with high 5-HTT expression, there was a strong
      correlation between theta power and the amplitude of the hemodynamic response.
      CONCLUSIONS: Direct experimental manipulation of 5-HTT expression levels
      throughout the brain markedly altered fear learning, amygdala hemodynamic
      responses, and neuronal oscillations.

PMID- 24120095
TI  - Learning about oxytocin: pharmacologic and behavioral issues.
AB  - Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT)
      plays a role in neuropsychiatric disorders characterized by social dysfunction,
      the influence of OT on the nonsocial aspects of learning and memory have been
      less investigated. To foster research in this area, we review the effects of OT
      on learning and memory in animal models and humans. In healthy animal models, OT
      improves memory consolidation and extinction, but only if given at a low dose
      immediately after the acquisition phase. On the contrary, OT effects in healthy
      humans have been inconsistent; although, in this case, OT was always given before
      the acquisition phase and no dose-response curves have ever been drawn up.
      Interestingly, a specific impairment in the reversal of learning has been found
      in mice devoid of OT receptors and OT has been demonstrated to enhance fear
      extinction in rodents. All together, these data suggest that OT plays a role in
      elementary forms of behavioral flexibility and adaptive responses and support its
      therapeutic potential in neuropsychiatric disorders characterized by cognitive
      inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease,
      Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has
      been shown to improve cognitive flexibility in OT receptor-deficient mice, and
      scattered findings indicate that intranasal OT has positive effects on the memory
      of patients with schizophrenia or posttraumatic stress disorders. Further studies
      of the therapeutic potential of OT as an enhancer of learning and memory are
      warranted. 

PMID- 24120094
TI  - Oxytocin receptor genotype modulates ventral striatal activity to social cues and
      response to stressful life events.
AB  - BACKGROUND: Common variants in the oxytocin receptor gene (OXTR) have been shown
      to influence social and affective behavior and to moderate the effect of adverse
      experiences on risk for social-affective problems. However, the intermediate
      neurobiological mechanisms are not fully understood. Although human functional
      neuroimaging studies have reported that oxytocin effects on social behavior and
      emotional states are mediated by amygdala function, animal models indicate that
      oxytocin receptors in the ventral striatum (VS) modulate sensitivity to social
      reinforcers. This study aimed to comprehensively investigate OXTR-dependent brain
      mechanisms associated with social-affective problems. METHODS: In a sample of
      1445 adolescents we tested the effect of 23-tagging single nucleotide
      polymorphisms across the OXTR region and stressful life events (SLEs) on
      functional magnetic resonance imaging blood oxygen level-dependent activity in
      the VS and amygdala to animated angry faces. Single nucleotide polymorphisms for
      which gene-wide significant effects on brain function were found were then
      carried forward to examine associations with social-affective problems. RESULTS:
      A gene-wide significant effect of rs237915 showed that adolescents with minor CC
      genotype had significantly lower VS activity than CT/TT-carriers. Significant or
      nominally significant gene * environment effects on emotional problems (in girls)
      and peer problems (in boys) revealed a strong increase in clinical symptoms as a
      function of SLEs in CT/TT-carriers but not CC-homozygotes. However, in low-SLE
      environments, CC-homozygotes had more emotional problems (girls) and peer
      problems (boys). Moreover, among CC-homozygotes, reduced VS activity was related
      to more peer problems. CONCLUSIONS: These findings suggest that a common OXTR
      variant affects brain responsiveness to negative social cues and that in "risk
      carriers" reduced sensitivity is simultaneously associated with more social
      affective problems in "favorable environments" and greater resilience against
      stressful experiences.

PMID- 24120096
TI  - FRET-based sensor analysis reveals caveolae are spatially distinct Ca2+ stores in
      endothelial cells.
AB  - Ca2+-regulating and Ca2+-dependent molecules enriched in caveolae are typically
      shaped as plasmalemmal invaginations or vesicles. Caveolae structure and
      subcellular distribution are critical for Ca2+ release from endoplasmic reticulum
      Ca2+ stores and for Ca2+ influx from the extracellular space into the cell.
      However, Ca2+ dynamics inside caveolae have never been directly measured and
      remain uncharacterized. To target the fluorescence resonance energy transfer
      (FRET)-based Ca2+ sensing protein D1, a mutant of cameleon, to the intra-caveolar
      space, we made a cDNA construct encoding a chimeric protein of lectin-like
      oxidized low-density lipoprotein receptor 1 (LOX-1) and D1 (LOXD1).
      Immunofluorescence and immunoelectron microscopy confirmed that a significant
      portion of LOXD1 was localized with caveolin-1 at morphologically apparent
      caveolar vesicles in endothelial cells. LOXD1 detected ATP-induced transient Ca2+
      decreases by confocal FRET imaging in the presence or absence of extracellular
      Ca2+. This ATP-induced Ca2+ decrease was abolished following knockdown of caveoin
      1, suggesting an association with caveolae. The X-ray spectra obtained by the
      spot analysis of electron-opaque pyroantimonate precipitates further confirmed
      that ATP-induced calcium decreases in intra-caveolar vesicles. In conclusion,
      subplasmalemmal caveolae function as Ca2+-releasable Ca2+ stores in response to
      ATP. This intracellular local Ca2+ delivery system may contribute to the complex
      spatiotemporal organization of Ca2+ signaling.

PMID- 24120097
TI  - [Periorificial and acral lesions].

PMID- 24120099
TI  - [Reply].

PMID- 24120098
TI  - [Association between inflammatory markers and microbial translocation in patients
      with human immunodeficiency virus infection taking antiretroviral treatment].
AB  - BACKGROUND AND OBJECTIVE: Inflammatory biomarkers are increased in patients with
      human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART)
      improves some parameters but do not normalize them. The aim of this study is to
      determine those factors (including microbial translocation) associated with
      higher inflammation in HIV treated patients. PATIENTS AND METHODS: Transversal
      observational study. INCLUSION CRITERIA: HIV patients receiving ART with an HIV
      viral load (VL)<400 copies/mL. Selection of patients: consecutively between
      November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL
      6) and tumour necrosis factor alpha (TNF-alpha). Main explanatory variable:
      microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6
      or TNF-alpha levels above percentile 75 (group 1) were compared with the rest of
      patients (group 2). Odds ratio (OR) were determined. RESULTS: Eighty-one patients
      were included (73% male, median age 45 years, 48% stage C). Twenty-six percent
      had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV
      VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with
      the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77,
      P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15,
      P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR
      62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). CONCLUSIONS: In
      patients with HIV infection receiving treatment, the higher levels of
      inflammatory markers are associated with microbial translocation and past
      cardiovascular events.

PMID- 24120100
TI  - [Reply].

PMID- 24120101
TI  - [Consensus conference: Treatment of type 2 diabetes in the elderly].

PMID- 24120102
TI  - [Regulation of specimen from corpses].

PMID- 24120103
TI  - [Ability of procalcitonin to predict bacteremia in patients with community
      acquired pneumonia].
AB  - BACKGROUND AND OBJECTIVE: To analyze the usefulness and ability of procalcitonin
      (PCT) to predict the presence of bacteremia in patients with community-acquired
      pneumonia (CAP) caused by Streptococcus pneumoniae (S. pneumoniae) or other
      bacteria. PATIENTS AND METHOD: This is an observational, prospective and
      descriptive study involving patients who were diagnosed with CAP in our Emergency
      Department. Data collected included socio-demographic and comorbidity variables,
      Charlson index, stage in the Pneumonia Severity Index and criteria of severe NAC,
      microbiologic studies and biomarker determinations (PCT and C reactive protein).
      The follow-up was carried out during 30 days to calculate the predictive power
      and the diagnostic performance for bacteremia caused or not by S. pneumoniae.
      RESULTS: Four hundred and seventy-four patients were finally included in the
      study. Blood cultures were positive in 85 individuals (17.9%) and S. pneumoniae
      was identified as the responsible pathogen in 75 of them (88.4%) (in 5 cases
      together with another agent). The area under the Receiver Operating
      Characteristic curve for PCT to predict bacteremia (caused by S. pneumoniae or
      not) was 0.988 (95% confidence interval 0.908-0.995; P<.001) and, considering a
      cut-off value>=0.95ng/mL, the negative predictive value and the positive
      likelihood ratio were>98% and>10, respectively. The most frequently isolated
      serotypes of S. pneumoniae were 19A, 7F, 1 and 3. The highest mean levels of PCT
      were found in serotypes 7F, 19A, 3 and 1, which showed statistically significant
      differences with regard to the others serotypes considered (P=.008). Serotypes
      associated with the highest percentage of severe sepsis-septic shock, 30-days
      mortality and multi-lobe or bilateral affection were 3, 1 and 19A; 1, 3 and 19A;
      and 3, 19A and 6A, respectively. CONCLUSIONS: PCT had a remarkable diagnostic
      ability to discard or suspect bacteremia and to guide the etiology of CAP caused
      by S. pneumoniae. Serotypes 1, 3, 19A and 7F showed greater frequency, systemic
      inflammatory response and clinical severity.

PMID- 24120104
TI  - [Influence of age on the clinical manifestations of invasive pneumococcal disease
      and antibiotic resistance rates].
AB  - BACKGROUND AND OBJECTIVE: Invasive pneumococcal disease (IPD) shows different
      epidemiological characteristics depending on age and pneumococcus serotype. The
      aims of the work were to analyze the clinical manifestations and mortality
      associated with IPD, the serotype isolated and the antibiotic resistance rates in
      different age groups. PATIENTS AND METHOD: Retrospectively, 141 patients with IPD
      diagnosed between 2002 and 2008 were studied. Patients were classified in 4 age
      groups: <= 2 year-old, 3-14 year-old, 15-64 year-old and >= 65 year-old. RESULTS:
      Pneumonia was the most common manifestation in all age groups (71%). Pneumococcal
      meningitis was more prevalent in patients <= 2 year-old (28 vs. 9%, P=.054) and
      empyema was more frequent in those between 3-14 year-old (31 vs. 5%, P<.001).
      Mortality was associated with age >= 65 year-old (odds ratio [OR] 7, 95%
      confidence interval [95% CI] 1.9-28.9), primary bacteremia (OR 7, 95% CI 1.9
      28.9) and orotracheal intubation (OR 9, 95% CI 1.9-41.1). The more prevalent
      serotypes among patients <= 2 year-old were 14, 19A and 19F. The serotype 1 was
      most common in patients between 3-14 year-old and serotype 3 in those >= 65 year
      old. A higher rate of non-susceptible penicillin strains was observed in
      pediatric population (42 vs. 19%, P=.007). CONCLUSIONS: Age was related to the
      clinical manifestations, mortality and antibiotic resistance rates. Primary
      bacteremia was one of the risk factors of mortality.

PMID- 24120105
TI  - [Hyaluronic acid instillation as treatment of haematuria due to radiation induced
      cystitis].

PMID- 24120106
TI  - [Venous and arterial thrombosis: similarities and clinical implications].

PMID- 24120107
TI  - [Reply].

PMID- 24120108
TI  - [Intravenous bisphosphonates for bone Paget's disease: higher risk of adverse
      events].

PMID- 24120109
TI  - [Chronic spontaneous urticaria].

PMID- 24120110
TI  - [Screening of anal intraepithelial neoplasia in risk groups: descriptive study of
      sexual habits and other sexual transmitted infections].
AB  - BACKGROUND: Anal intraepithelial neoplasia is considered a precursor lesion of
      anal squamous carcinoma. The population with increased risk of this conditions
      are immunocompromised individuals, especially HIV-infected, with anal sex
      practices. The aim of this study was to describe the sexual habits of patients
      who were seen in sexually transmitted infections (STIs) consult in our service in
      whom anal cytology was performed as well as the association of anal dysplasia to
      other STIs. MATERIAL AND METHODS: We performed a retrospective cohort study that
      included those patients in whom, according to our protocol, anal cytology was
      performed between 2008 and 2011. Also we conducted a survey on sexual habits and
      screening for other STIs. Finally, we conducted a descriptive and analytical
      study assessing bivariate distribution of cytological alterations and grade of
      anal dysplasia. RESULTS: A total of 347 anal cytologies were performed, and 48.1%
      were abnormal. Statistically significant differences were found between the
      presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis
      infection and the presence of cytologic alterations. CONCLUSION: There was a high
      incidence of anal dysplasia in our group of individuals with risky sexual habits;
      however, it is probably underdiagnosed due to its subclinical nature and lack of
      a well-established screening protocol.

PMID- 24120111
TI  - First meeting: "Latin American Network on Molecular Epidemiology and Evolutionary
      Genetics of Infectious Diseases (LAN-MEEGID)": La Paz, Bolivia, 25th-27th April
      2012.

PMID- 24120112
TI  - International BioInformatics Workshop on Virus Evolution and Molecular
      Epidemiology.

PMID- 24120113
TI  - Overexpression of microRna-200c in CD44+CD133+ CSCS inhibits the cellular
      migratory and invasion as well as tumorigenicity in mice.
AB  - Cancer stem cells (CSCs) are believed to be responsible for drug resistance,
      metastasis of tumors. To investigate the biological characteristics of
      CD44+CD133+CSCs with over- expressing microRNA-200c (miR-200c), and to provide
      evidences for miR-200c as a tumor suppressor to treat melanoma. CD44+CD133+CSCs
      were isolated from the mouse melanoma B16F10 cell line by using immune magnetic
      activated cell sorting. The lentivirus miR-200c was transduced into the cells,
      and the effect of miR-200c overexpression on the biological characteristics of
      B16F10 CD44+ CD133+CSCs was analyzed by a series assays. The stable
      overexpression of miR-200c in B16F10 CD44+CD133+CSCs obviously resulted in
      downregulation of zinc-finger E-box binding homeobox 1 expression, reduction of
      the cell proliferation, colony forming, cell migratory and invasion ability in
      vitro as well as tumorigenicity in vivo compared with those of the B16F10 cells
      and B16F10 non-CD44+ CD133+CSCs. These findings suggest that the miR-200c
      overexpression as a novel strategy to target therapy of melanoma CSCs.

PMID- 24120114
TI  - DNA double-strand break repair is activated in carotid artery restenosis.
AB  - Carotid stenosis is a narrowing or constriction of the inner surface of the
      carotid artery, usually caused by atherosclerosis. In the past decades, carotid
      angioplasty and stenting (CAS) has been developed into a credible option for the
      patients with carotid stenosis. However, restenosis remains a severe and unsolved
      issue after CAS treatment. Currently, the molecular mechanisms involved in the
      restenosis are still largely unclear. In this study, we found that the double
      strand DNA breaks (DSBs) were induced by oxidative stress in the human carotid
      artery with restenosis by examining the level of gammaH2AX in the artery tissues.
      We further analyzed the activation of DNA damage repair pathways in the carotid
      restenosis. Our results suggest that non-homologues end joining (NHEJ), but not
      homologous recombination (HR), is mainly activated in the artery tissues with
      restenosis. Our results may provide clues to develop a new therapeutic strategy
      for carotid artery restenosis following CAS treatment.

PMID- 24120115
TI  - Benign cystic mesothelioma of the peritoneum: a case report and literature
      review.
AB  - Benign cystic mesothelioma of the peritoneum (BCM) is an uncommon lesion with
      some 130 cases reported since the first case described by Smith and Mennenmeyer
      in 1979. It is a rare intra abdominal tumor occurring predominantly in women of
      reproductive age. Due to the rarity of this tumor, similarity of patient
      presentation, and comparable features on imaging, the diagnosis of this pathology
      is difficult, and is based on histological findings. This tumor is known for
      local recurrence. It's agreed that surgery is the only effective treatment, but
      there are no evidence-based treatment strategies for BCM. 

PMID- 24120116
TI  - Determination of biogas generation potential as a renewable energy source from
      supermarket wastes.
AB  - Fruit, vegetable, flower waste (FVFW), dairy products waste (DPW), meat waste
      (MW) and sugar waste (SW) obtained from a supermarket chain were anaerobically
      digested, in order to recover methane as a source of renewable energy. Batch
      mesophilic anaerobic reactors were run at total solids (TS) ratios of 5%, 8% and
      10%. The highest methane yield of 0.44 L CH4/g VS(added) was obtained from
      anaerobic digestion of wastes (FVFW+DPW+MW+SW) at 10% TS, with 66.4% of methane
      (CH4) composition in biogas. Anaerobic digestion of mixed wastes at 5% and 8% TS
      provided slightly lower methane yields of 0.41 and 0.40 L CH4/g VS(added),
      respectively. When the wastes were digested alone without co-substrate addition,
      the highest methane yield of 0.40 L CH4/g VS(added) was obtained from FVFW at 5%
      TS. Generally, although the volatile solids (VS) conversion percentages seemed
      low during the experiments, higher methane yields could be obtained from
      anaerobic digestion of supermarket wastes. A suitable carbon/nitrogen (C/N)
      ratio, proper adjustment of the buffering capacity and the addition of essential
      trace nutrients (such as Ni) could improve VS conversion and biogas production
      yields significantly.

PMID- 24120117
TI  - Influence of microorganism content in suspended particles on the particle-water
      partitioning of mercury in semi-enclosed coastal waters.
AB  - It is known that particle scavenging of mercury (Hg) can be affected by the
      abundance of particulate organic matter in coastal waters. However, the role of
      living organic particles in Hg scavenging is not yet completely understood. In
      this study, we hypothesized that an abundance of living organic particles (i.e.,
      phytoplankton and bacteria) would influence the particle-water partitioning of Hg
      in coastal waters. Surface seawater samples were collected from eight stations in
      Gwangyang Bay, Korea, in three seasons (November 2009, April 2010, and October
      2010) for the determination of concentrations of suspended particulate matter
      (including chlorophyll-a and bacteria), and Hg in unfiltered and filtered waters.
      We found that more Hg partitioned toward particulate matter when phytoplankton
      biomass, indicated from the chlorophyll-a concentration in a particle, was
      higher. In the low algal season, when [chlorophyll-a]<0.6 MUg L(-1), the
      bacterial number, instead of chlorophyll-a concentration in particle, showed a
      positive correlation with the particle-water partition coefficient of Hg.
      Overall, microbial abundance seems to play a critical role in particle scavenging
      of Hg in coastal water. Taking this result in light of Hg in pristine coastal
      zones, we predict that increases in algal biomass amplify the potential for algae
      to transfer Hg to marine food chains.

PMID- 24120118
TI  - Escalation of cocaine intake and incubation of cocaine seeking are correlated
      with dissociable neuronal processes in different accumbens subregions.
AB  - BACKGROUND: Cocaine addiction is characterized by a progressive increase in drug
      intake and a persistent craving for the drug during prolonged abstinence. Whether
      these two prominent features of cocaine addiction are related to each other and
      are mediated by similar or different neuronal processes is currently unknown.
      METHODS: Rats were first allowed to self-administer cocaine under long-access (6
      hour) conditions to induce escalation of cocaine intake. Self-administration
      sessions were designed to measure both drug seeking and drug taking. After
      escalation, rats underwent a 1-month period of forced abstinence after which they
      were re-exposed to cocaine to induce re-escalation of cocaine intake. In vivo
      electrophysiologic recordings were conducted in the core and shell subregions of
      the nucleus accumbens (NAc) during cocaine intake escalation, after abstinence
      and during re-escalation. RESULTS: After abstinence, escalated levels of cocaine
      taking decreased toward pre-escalation levels, whereas cocaine seeking increased
      persistently. These opposite postabstinence changes were uncorrelated. At the
      neuronal level, the postabstinence decrease in cocaine taking was correlated with
      a normalization of depressed neuronal activity in the NAc shell that had
      developed during escalation of cocaine intake. In contrast, the incubation-like
      increase in cocaine seeking was selectively correlated with a persistent increase
      in the proportion of neurons in the NAc core that phasically fire during cocaine
      seeking. CONCLUSIONS: These findings show that cocaine taking and cocaine seeking
      evolve differently during abstinence from extended drug use and depend on
      dissociable neuronal processes in different subregions of the nucleus accumbens.

PMID- 24120120
TI  - Three-year follow-up of serum 25-hydroxyvitamin D, parathyroid hormone, and bone
      mineral density in nursing home residents who had received 12 months of daily
      bread fortification with 125 MUg of vitamin D3.
AB  - BACKGROUND: We conducted a single-arm clinical trial in institutionalized
      seniors, on the effects of high-dose vitamin D3-fortified bread daily intake
      (clinicaltrials.gov registration NCT00789503). METHODS: At 1 and 3 years after
      the dietary fortification was stopped, serum 25-hydroxyvitamin D (25(OH)D),
      parathyroid hormone (PTH) and bone mineral density were measured in 23 of the
      original study subjects, aged 60-82 years who had consumed bread buns (100 g)
      fortified with 320 mg elemental calcium and 125 MUg (5,000 IU) vitamin D3 daily
      for one year. RESULTS: At the end of the 1-year supplementation phase (receiving
      vitamin D3 fortified bread daily), mean (SD) serum 25(OH)D was 127.3 +/- 37.8
      nmol/L (baseline for this follow-up). At 1-year follow-up, the serum 25(OH)D was
      64.9 +/- 24.8 nmol/L (p = 0.001, vs. baseline); and at 3-year follow-up it was
      28.0 +/- 15.0 nmol/L (p = 0.001 vs. baseline). Serum PTH was 18.8 +/- 15.6 pg/ml
      at baseline while at Year 3 it was 48.4 +/- 18.4 pg/ml (p = 0.001 vs. baseline).
      Lumbar spine BMD did not change from baseline to Year 3. However, by Year 3, hip
      BMD had decreased (0.927 +/- 0.130 g/cm2 vs. 0.907 +/- 0.121 g/cm2, p = 0.024).
      CONCLUSION: Vitamin D nutritional status exhibits a long half-life in the body,
      and a true steady-state plateau may not even be reached 1 year after a
      discontinuation in dose. Furthermore, once the need for vitamin D has been
      established, based on a low baseline serum 25(OH)D concentrations, the
      appropriate action is to maintain corrective vitamin D supplementation over the
      long term.

PMID- 24120119
TI  - Body mass index-related regional gray and white matter volume reductions in first
      episode mania patients.
AB  - BACKGROUND: We previously reported that overweight/obese first-episode mania
      patients had reduced white matter (WM) and temporal lobe volumes compared with
      normal-weight patients. WM reductions are characteristic of early-stage bipolar
      disorder (BD), whereas temporal lobe reductions are frequently reported later in
      the illness. These findings thus suggested a testable hypothesis: that the
      neuropathology of BD is exacerbated with elevated body mass index (BMI). METHODS:
      We used voxel-based morphometry to examine the relationship between BMI and
      regional gray matter (GM) and WM volumes in our sample of 57 euthymic first
      episode mania patients and 55 healthy subjects. We hypothesized that elevated BMI
      in patients, but not healthy subjects, would be associated with volume reductions
      in frontal, temporal, and subcortical limbic brain regions implicated in the
      pathophysiology of BD. RESULTS: At recovery from their first manic episode,
      patients with higher BMI had GM and WM reductions in the predicted emotion
      generating and -regulating regions. In contrast, healthy subjects with higher BMI
      had reduced occipital lobe GM only. Factorial analyses confirmed significant BMI
      * diagnosis interactions for the WM reductions. Approximately three-quarters of
      patients with elevated BMI were overweight rather than obese; thus, weight
      related volume reductions were detectable in patients with modestly elevated BMI.
      CONCLUSIONS: This is the first hypothesis-driven test of, and supporting evidence
      for, our theory that elevated BMI is associated with unique brain changes in BD
      that have a negative impact on regions believed to be vulnerable in the illness.
      Our results suggest a neurobiological mechanism to explain the well-validated
      link between obesity and illness severity in BD.

PMID- 24120121
TI  - Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL
      10.
AB  - Activation of the platelet-activating factor receptor (PAFR) in macrophages is
      associated with suppressor phenotype. Here, we investigated the PAFR in murine
      dendritic cells (DC). Bone marrow-derived dendritic cells (BALB/c) were cultured
      with GM-CSF and maturation was induced by LPS. The PAFR antagonists (WEB2086,
      WEB2170, PCA4248) and the prostaglandin (PG) synthesis inhibitors (indomethacin,
      nimesulide and NS-398) were added before LPS. Mature and immature DCs expressed
      PAFR. LPS increased MHCII, CD40, CD80, CD86, CCR7 and induced IL-10, IL-12, COX-2
      and PGE2 expression. IL-10, COX-2 and PGE2 levels were reduced by PAFR
      antagonists and increased by cPAF. The IL-10 production was independent of PGs.
      Mature DCs induced antigen-specific lymphocyte proliferation. PAFR antagonists or
      PG-synthesis inhibitors significantly increased lymphocyte proliferation. It is
      proposed that PAF has a central role in regulatory DC differentiation through
      potentiation of IL-10 and PGE2 production. 

PMID- 24120122
TI  - Dietary Salba (Salvia hispanica L) seed rich in alpha-linolenic acid improves
      adipose tissue dysfunction and the altered skeletal muscle glucose and lipid
      metabolism in dyslipidemic insulin-resistant rats.
AB  - This work reports the effect of dietary Salba (chia) seed rich in n-3 alpha
      linolenic acid on the morphological and metabolic aspects involved in adipose
      tissue dysfunction and the mechanisms underlying the impaired glucose and lipid
      metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats
      were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while
      in the other half, corn oil (CO) was replaced by chia seed for 3 months
      (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO
      by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size
      distribution, improved lipogenic enzyme activities, lipolysis and the anti
      lipolytic action of insulin. In the skeletal muscle lipid storage, glucose
      phosphorylation and oxidation were normalized. Chia seed reversed the impaired
      insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and
      GLUT-4 protein levels as well as insulin resistance and dyslipidemia. 

PMID- 24120123
TI  - Plasma sulfur amino acids and stearoyl-CoA desaturase activity in two Caucasian
      populations.
AB  - In rats, dietary restriction of the cysteine precursor methionine suppresses
      hepatic stearoyl-CoA desaturase (SCD)-1 expression and activity, whereas cysteine
      supplementation reverses these effects. In 2 independent cohorts: Hordaland
      Health Study (HUSK; N=2021, aged 71-74y), Norway, and Hoorn study (N=686, aged 50
      87y), Netherlands, we examined the cross-sectional associations of plasma sulfur
      containing compounds (SCC; methionine, S-adenosylmethionine, S
      adenosylhomocysteine, homocysteine, cystathionine, total cysteine (tCys),
      glutathione and cysteinylglycine) with SCD-16 index (16:1n-7/16:0), estimated
      from fatty acid profiles of total plasma or serum lipids. Only tCys was
      consistently associated with SCD-16 index after adjustments for sex and age
      (HUSK: partial r=0.14; Hoorn: partial r=0.11, P<0.001 for both), and after
      further adjustments for other SCC, body fat, diet, exercise and plasma lipids
      (HUSK: partial r=0.07, P=0.004; Hoorn: partial r=0.12, P=0.013). Together with
      animal data showing an effect of dietary cysteine on SCD1, our results suggest a
      role for cysteine in SCD1 regulation in humans. 

PMID- 24120124
TI  - Why pediatricians fail to diagnose hypertension: a multicenter survey.
AB  - OBJECTIVE: To elucidate why pediatricians fail to diagnose childhood
      hypertension, with special emphasis on the use of blood pressure (BP) reference
      data. We hypothesized that pediatricians frequently omit BP measurements and do
      not routinely relate BP measurements to reference data. STUDY DESIGN: We
      conducted a multicenter survey on BP measurement among 197 participants.
      Respondents were asked to estimate BP percentiles and classify BP readings in 12
      example cases. Questionnaires were completed onsite in the presence of the
      researchers, without access to BP reference data. RESULTS: We found that 71% of
      physicians measure BP during ambulatory visits only if the child has risk factors
      for hypertension. After measuring BP, 65% compare the reading with reference data
      only if they suspect that it is elevated. Their ability to rate a reading at its
      true value is limited, however; 47% of the physicians classified 1 or more of the
      prehypertensive or hypertensive cases as normal. CONCLUSIONS: Most pediatricians
      do not screen for hypertension, contrary to recommendations. After obtaining a BP
      measurement, the majority do not compare the reading with reference standards;
      however, without the use of reference data, they commonly underestimate the BP
      percentile and potentially miss cases of childhood hypertension.

PMID- 24120125
TI  - Less invasive versus conventional heart valve surgery in patients with severe
      heart failure.
AB  - OBJECTIVE: Patients with severe heart failure might benefit from reduced
      operative trauma, but rarely undergo less-invasive valve surgery. The present
      study compared the outcomes of less-invasive heart valve surgery with those of
      complete sternotomy in such patients. METHODS: From January 1995 to July 2010,
      871 patients in New York Heart Association class III or IV underwent valve
      surgery (aortic or mitral, or both). A less-invasive approach was used in 205.
      Propensity score matching yielded 185 matched pairs for outcomes comparison
      adjusted for patient characteristics and 139 pairs adjusted further for
      individual surgeon. RESULTS: Without considering surgeons, myocardial ischemic
      times (59 +/- 27 vs 64 +/- 26 minutes, P = .04), cardiopulmonary bypass times (75
      +/- 35 vs 86 +/- 34 minutes, P < .0001), and intensive care unit stays (median,
      24 vs 43 hours; P = .007) were shorter for less-invasive surgery. Hospital
      morbidity, mortality (1.6% [3 of 185] vs 2.7% [5 of 185]; P = .5), and long-term
      survival (53% and 48% at 12 years; P = .3) were similar. After considering the
      surgeon, these benefits were not apparent; rather, efficiency, safety, and
      effectiveness were equivalent to those of complete sternotomy. Thus, myocardial
      ischemic (63 +/- 30 vs 62 +/- 25 minutes, P = .8) and cardiopulmonary bypass (80
      +/- 40 vs 81 +/- 31 minutes, P = .5) times were similar, as were intensive care
      unit stay (median, 28 vs 30 hours; P = .09), postoperative complications, in
      hospital mortality (2.2% [3 of 139] vs 3.6% [5 of 139]; P = .5), and long-term
      survival (57% and 53% at 12 years; P = .5). CONCLUSIONS: In selected patients
      with severe heart failure, less-invasive valve surgery is a viable option,
      yielding at least equivalent efficiency, safety, and effectiveness to complete
      sternotomy. However, achieving these outcomes requires surgeons experienced in
      less-invasive surgery.

PMID- 24120126
TI  - The missing link between itch and inflammation in atopic dermatitis.
AB  - Atopic dermatitis is a common skin disease with high morbidity and is associated
      with severe itch and chronic skin inflammation. In this issue of Cell, Wilson et
      al. demonstrate that epithelial cells communicate directly with cutaneous sensory
      neurons via a cytokine to induce itch. 

PMID- 24120127
TI  - SAX-7 and menorin light the path for dendrite morphogenesis.
AB  - Environmental and cellular cues pattern dendritic growth and direct dendrites to
      their targets. However, little is known about the signals regulating interactions
      with the surrounding substrate. Dong et al. and Salzberg et al. now identify a
      tripartite ligand-receptor complex that conveys cues from the substrate necessary
      for the patterning of complex dendrites in C. elegans. 

PMID- 24120128
TI  - Remembrance of cilia past.
AB  - The primary cilium is thought to be disassembled prior to mitosis, freeing the
      centrosomes to participate in the mitotic spindle. In this issue, Paridaen et al.
      demonstrate that a remnant of the ciliary membrane remains attached to the mother
      centriole and is asymmetrically inherited in the developing neocortex. 

PMID- 24120129
TI  - Singular expression of olfactory receptor genes.
AB  - Understanding the mechanisms of monogenic and monoallelic transcription of the
      large repertoire of olfactory receptor genes represents a challenging task. A
      picture is now emerging in which odorant receptor choice and stabilization
      involve an escape from silencing followed by the activation of an unconventional
      feedback loop. 

PMID- 24120130
TI  - Mechano-gated ion channels in sensory systems.
AB  - Living organisms sense their physical environment through cellular
      mechanotransduction, which converts mechanical forces into electrical and
      biochemical signals. In turn, signal transduction serves a wide variety of
      functions, from basic cellular processes as diverse as proliferation,
      differentiation, migration, and apoptosis up to some of the most sophisticated
      senses, including touch and hearing. Accordingly, defects in mechanosensing
      potentially lead to diverse diseases and disorders such as hearing loss,
      cardiomyopathies, muscular dystrophies, chronic pain, and cancer. Here, we review
      the status of mechanically activated ion channel discovery and discuss current
      challenges to define their properties and physiological functions. 

PMID- 24120131
TI  - An extracellular adhesion molecule complex patterns dendritic branching and
      morphogenesis.
AB  - Robust dendrite morphogenesis is a critical step in the development of
      reproducible neural circuits. However, little is known about the extracellular
      cues that pattern complex dendrite morphologies. In the model nematode
      Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly
      branched dendrite morphology. Here, we report the identification of a tripartite
      ligand-receptor complex of membrane adhesion molecules that is both necessary and
      sufficient to instruct spatially restricted growth and branching of PVD
      dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations
      in the surrounding hypodermal tissue, whereas DMA-1 acts as the cognate receptor
      on PVD. Mutations in this complex lead to dramatic defects in the formation,
      stabilization, and organization of the dendritic arbor. Ectopic expression of SAX
      7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a
      DMA-1-dependent manner. Both in vivo and in vitro experiments indicate that all
      three molecules are needed for interaction. 

PMID- 24120132
TI  - Skin-derived cues control arborization of sensory dendrites in Caenorhabditis
      elegans.
AB  - Sensory dendrites depend on cues from their environment to pattern their growth
      and direct them toward their correct target tissues. Yet, little is known about
      dendrite-substrate interactions during dendrite morphogenesis. Here, we describe
      MNR-1/menorin, which is part of the conserved Fam151 family of proteins and is
      expressed in the skin to control the elaboration of "menorah"-like dendrites of
      mechanosensory neurons in Caenorhabditis elegans. We provide biochemical and
      genetic evidence that MNR-1 acts as a contact-dependent or short-range cue in
      concert with the neural cell adhesion molecule SAX-7/L1CAM in the skin and
      through the neuronal leucine-rich repeat transmembrane receptor DMA-1 on sensory
      dendrites. Our data describe an unknown pathway that provides spatial information
      from the skin substrate to pattern sensory dendrite development nonautonomously. 

PMID- 24120133
TI  - Co-opting the unfolded protein response to elicit olfactory receptor feedback.
AB  - Olfactory receptor (OR) expression requires the transcriptional activation of 1
      out of 1,000s of OR alleles and a feedback signal that preserves this
      transcriptional choice. The mechanism by which olfactory sensory neurons (OSNs)
      detect ORs to signal to the nucleus remains elusive. Here, we show that OR
      proteins generate this feedback by activating the unfolded protein response
      (UPR). OR expression induces Perk-mediated phosphorylation of the translation
      initiation factor eif2alpha causing selective translation of activating
      transcription factor 5 (ATF5). ATF5 induces the transcription of adenylyl cyclase
      3 (Adcy3), which relieves the UPR. Our data provide a role for the UPR in
      defining neuronal identity and cell fate commitment and support a two-step model
      for the feedback signal: (1) OR protein, as a stress stimulus, alters the
      translational landscape of the OSN and induces Adcy3 expression; (2), Adcy3
      relieves that stress, restores global translation, and makes OR choice permanent.

PMID- 24120134
TI  - Asymmetric inheritance of centrosome-associated primary cilium membrane directs
      ciliogenesis after cell division.
AB  - Primary cilia are key sensory organelles that are thought to be disassembled
      prior to mitosis. Inheritance of the mother centriole, which nucleates the
      primary cilium, in relation to asymmetric daughter cell behavior has previously
      been studied. However, the fate of the ciliary membrane upon cell division is
      unknown. Here, we followed the ciliary membrane in dividing embryonic neocortical
      stem cells and cultured cells. Ciliary membrane attached to the mother centriole
      was endocytosed at mitosis onset, persisted through mitosis at one spindle pole,
      and was asymmetrically inherited by one daughter cell, which retained stem cell
      character. This daughter re-established a primary cilium harboring an activated
      signal transducer earlier than the noninheriting daughter. Centrosomal
      association of ciliary membrane in dividing neural stem cells decreased at late
      neurogenesis when these cells differentiate. Our data imply that centrosome
      associated ciliary membrane acts as a determinant for the temporal-spatial
      control of ciliogenesis. 

PMID- 24120135
TI  - Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop
      formation.
AB  - We have applied a super-resolution fluorescence imaging method, stochastic
      optical reconstruction microscopy (STORM), to visualize the structure of
      functional telomeres and telomeres rendered dysfunctional through removal of
      shelterin proteins. The STORM images showed that functional telomeres frequently
      exhibit a t-loop configuration. Conditional deletion of individual components of
      shelterin showed that TRF2 was required for the formation and/or maintenance of t
      loops, whereas deletion of TRF1, Rap1, or the POT1 proteins (POT1a and POT1b) had
      no effect on the frequency of t-loop occurrence. Within the shelterin complex,
      TRF2 uniquely serves to protect telomeres from two pathways that are initiated on
      free DNA ends: classical nonhomologous end-joining (NHEJ) and ATM-dependent DNA
      damage signaling. The TRF2-dependent remodeling of telomeres into t-loop
      structures, which sequester the ends of chromosomes, can explain why NHEJ and the
      ATM signaling pathway are repressed when TRF2 is present. 

PMID- 24120136
TI  - Differentiated Troy+ chief cells act as reserve stem cells to generate all
      lineages of the stomach epithelium.
AB  - Proliferation of the self-renewing epithelium of the gastric corpus occurs almost
      exclusively in the isthmus of the glands, from where cells migrate
      bidirectionally toward pit and base. The isthmus is therefore generally viewed as
      the stem cell zone. We find that the stem cell marker Troy is expressed at the
      gland base by a small subpopulation of fully differentiated chief cells. By
      lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells
      are shown to generate entirely labeled gastric units over periods of months. This
      phenomenon accelerates upon tissue damage. Troy(+) chief cells can be cultured to
      generate long-lived gastric organoids. Troy marks a specific subset of chief
      cells that display plasticity in that they are capable of replenishing entire
      gastric units, essentially serving as quiescent "reserve" stem cells. These
      observations challenge the notion that stem cell hierarchies represent a "one-way
      street." 

PMID- 24120137
TI  - Identification of liver cancer progenitors whose malignant progression depends on
      autocrine IL-6 signaling.
AB  - Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to
      evolve from premalignant lesions in chronically damaged livers. However, it was
      never established that premalignant lesions actually contain tumor progenitors
      that give rise to cancer. Here, we describe isolation and characterization of HCC
      progenitor cells (HcPCs) from different mouse HCC models. Unlike fully malignant
      HCC, HcPCs give rise to cancer only when introduced into a liver undergoing
      chronic damage and compensatory proliferation. Although HcPCs exhibit a similar
      transcriptomic profile to bipotential hepatobiliary progenitors, the latter do
      not give rise to tumors. Cells resembling HcPCs reside within dysplastic lesions
      that appear several months before HCC nodules. Unlike early hepatocarcinogenesis,
      which depends on paracrine IL-6 production by inflammatory cells, due to
      upregulation of LIN28 expression, HcPCs had acquired autocrine IL-6 signaling
      that stimulates their in vivo growth and malignant progression. This may be a
      general mechanism that drives other IL-6-producing malignancies. 

PMID- 24120138
TI  - PKM2 isoform-specific deletion reveals a differential requirement for pyruvate
      kinase in tumor cells.
AB  - The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in
      regulating anabolic metabolism. To determine whether PKM2 is required for tumor
      formation or growth, we generated mice with a conditional allele that abolishes
      PKM2 expression without disrupting PKM1 expression. PKM2 deletion accelerated
      mammary tumor formation in a Brca1-loss-driven model of breast cancer. PKM2 null
      tumors displayed heterogeneous PKM1 expression, with PKM1 found in
      nonproliferating tumor cells and no detectable pyruvate kinase expression in
      proliferating cells. This suggests that PKM2 is not necessary for tumor cell
      proliferation and implies that the inactive state of PKM2 is associated with the
      proliferating cell population within tumors, whereas nonproliferating tumor cells
      require active pyruvate kinase. Consistent with these findings, variable PKM2
      expression and heterozygous PKM2 mutations are found in human tumors. These data
      suggest that regulation of PKM2 activity supports the different metabolic
      requirements of proliferating and nonproliferating tumor cells.

PMID- 24120139
TI  - A polymorphic p53 response element in KIT ligand influences cancer risk and has
      undergone natural selection.
AB  - The ability of p53 to regulate transcription is crucial for tumor suppression and
      implies that inherited polymorphisms in functional p53-binding sites could
      influence cancer. Here, we identify a polymorphic p53 responsive element and
      demonstrate its influence on cancer risk using genome-wide data sets of cancer
      susceptibility loci, genetic variation, p53 occupancy, and p53-binding sites. We
      uncover a single-nucleotide polymorphism (SNP) in a functional p53-binding site
      and establish its influence on the ability of p53 to bind to and regulate
      transcription of the KITLG gene. The SNP resides in KITLG and associates with one
      of the largest risks identified among cancer genome-wide association studies. We
      establish that the SNP has undergone positive selection throughout evolution,
      signifying a selective benefit, but go on to show that similar SNPs are rare in
      the genome due to negative selection, indicating that polymorphisms in p53
      binding sites are primarily detrimental to humans. 

PMID- 24120140
TI  - The bacterial effector VopL organizes actin into filament-like structures.
AB  - VopL is an effector protein from Vibrio parahaemolyticus that nucleates actin
      filaments. VopL consists of a VopL C-terminal domain (VCD) and an array of three
      WASP homology 2 (WH2) motifs. Here, we report the crystal structure of the VCD
      dimer bound to actin. The VCD organizes three actin monomers in a spatial
      arrangement close to that found in the canonical actin filament. In this
      arrangement, WH2 motifs can be modeled into the binding site of each actin
      without steric clashes. The data suggest a mechanism of nucleation wherein VopL
      creates filament-like structures, organized by the VCD with monomers delivered by
      the WH2 array, that can template addition of new subunits. Similarities with
      Arp2/3 complex and formin proteins suggest that organization of monomers into
      filament-like structures is a general and central feature of actin nucleation.

PMID- 24120141
TI  - The dynamics of signaling as a pharmacological target.
AB  - Highly networked signaling hubs are often associated with disease, but targeting
      them pharmacologically has largely been unsuccessful in the clinic because of
      their functional pleiotropy. Motivated by the hypothesis that a dynamic signaling
      code confers functional specificity, we investigated whether dynamic features may
      be targeted pharmacologically to achieve therapeutic specificity. With a virtual
      screen, we identified combinations of signaling hub topologies and dynamic signal
      profiles that are amenable to selective inhibition. Mathematical analysis
      revealed principles that may guide stimulus-specific inhibition of signaling
      hubs, even in the absence of detailed mathematical models. Using the NFkappaB
      signaling module as a test bed, we identified perturbations that selectively
      affect the response to cytokines or pathogen components. Together, our results
      demonstrate that the dynamics of signaling may serve as a pharmacological target,
      and we reveal principles that delineate the opportunities and constraints of
      developing stimulus-specific therapeutic agents aimed at pleiotropic signaling
      hubs. 

PMID- 24120143
TI  - SnapShot: Neuromodulation.

PMID- 24120144
TI  - Reassessment of scoring systems and prognostic factors for metastatic spinal cord
      compression.
AB  - BACKGROUND CONTEXT: The incidence of metastatic spinal cord compression (MSCC) is
      increasing, paralleling increasing life expectancy of patients. However,
      management of MSCC and relevance of scoring systems remain controversial.
      PURPOSE: The aims of our study were to analyze the feasibility and outcomes of
      spinal surgery, to identify prognostic factors for survival, and to assess the
      accuracy of scoring systems in patients with malignancies associated with MSCC.
      STUDY DESIGN: Retrospective analysis of all patients with MSCC operated in our
      institution. METHODS: Outcomes of surgery, prognostic factors for survival, and
      relevance of Tomita and Tokuhashi scores were investigated. RESULTS: One hundred
      forty-eight patients were included: 66% were hyperalgic (pain score >6) and
      Frankel score (FS) was decreased in 49%. Seventy-three percent of patients had
      laminectomy with spinal fixation. After surgery, pain decreased in 75% of cases,
      FS was improved in 31%, and 92% of patients were ambulatory. Postoperative
      complication rate was 16%. Median overall survival (OS) was 8.9 months (95%
      confidence interval, 4.4-13). Only Tokuhashi score was relevant, but predictive
      accuracy of survival was just 51%. In univariate analyses, hyperalgia (p=.001),
      primary tumor site, extrabone metastases (p<.001), Karnofsky performance status
      (KPS) less than 70 (p<.001), poor American Society of Anesthesiologist (ASA)
      score (p<.001) or FS (p=.01), and absence of postoperative chemotherapy (p<.001)
      were associated with shorter OS. In multivariate analysis, only extrabone
      metastases (p=.004), KPS (p=.001), and ASA score (p=.007) remained significantly
      associated with OS. CONCLUSIONS: Surgery for MSCC is associated with limited
      morbidity, improved autonomy, and pain relief. Usual scores do not seem relevant,
      whereas ASA score, KPS, and extrabone metastases are significantly associated
      with OS.

PMID- 24120145
TI  - Risk factors associated with upper extremity palsy after expansive open-door
      laminoplasty for cervical myelopathy.
AB  - BACKGROUND CONTEXT: Postoperative paresis, so-called C5 palsy, of the upper
      extremities is a common complication of cervical surgery. There have been several
      reports about upper extremity palsy after cervical laminoplasty for patients with
      cervical myelopathy. However, the possible risk factors remain unclear. PURPOSE:
      To investigate the factors associated with the development of upper extremity
      palsy after expansive open-door laminoplasty for cervical myelopathy. STUDY
      DESIGN: A retrospective review of medical records. PATIENT SAMPLE: A total of 102
      patients (76 men and 26 women) were eligible for analysis in this study. The mean
      age of the patients was 58.7 years (range 35-81 years). Sixteen patients (13 men
      and 3 women, average age 62.8 years) with palsy were categorized as Group P, and
      eighty-six patients (63 men and 23 women, average age 57.8 years) without palsy
      as Group C. OUTCOME MEASURES: The demographic data collected from both groups
      were age, sex, duration of symptoms, disease, and type of surgical procedure.
      Cervical curvature index, width of the intervertebral foramen (WIF) at C5,
      anterior protrusion of the superior articular process (APSAP), number of
      compressed segments, high-signal intensity zone at the level corresponding to C3
      C5 (HIZ:C3-C5), and posterior shift of the spinal cord (PSSC) were also
      evaluated. METHODS: Upper extremity palsy was defined as weakness of Grade 4 or
      less of the key muscles in the upper extremity by manual muscle test without any
      deterioration of myelopathic symptoms after surgery. Comparisons were made with
      screen for the parameters with significant differences, and then we further
      analyzed these parameters by logistic regression analysis (the forward method) to
      verify the risk factors of the upper extremity palsy. RESULTS: Significant
      differences in diagnosis, the type of procedure, WIF, APSAP, and HIZ:C3-C5 were
      observed between the two groups. No statistical difference in PSSC between the
      groups was noted (2.06 vs. 2.53 mm, p=.247). In logistic regression analysis,
      ossification of the posterior longitudinal ligament (OPLL), cervical open-door
      laminoplasty together with posterior instrumented fusion (CLP+PIF), and WIF were
      found to be significant risk factors for postoperative upper extremity palsy.
      CONCLUSIONS: Patients with preoperative foraminal stenosis, OPLL, and additional
      iatrogenic foraminal stenosis because of CLP+PIF were more likely to develop
      postoperative upper extremity palsy. Attention should be given to the WIF
      determined on preoperative computed tomography of the C5 root. To prevent
      iatrogenic foraminal stenosis, appropriate distraction between spine segments
      should be provided during placement of the rod.

PMID- 24120146
TI  - Prognosis of spontaneous thoracic curve correction after the selective anterior
      fusion of thoracolumbar/lumbar (Lenke 5C) curves in idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Prognosis of minor lumbar curve correction after selective
      thoracic fusion in idiopathic scoliosis is well defined. However, the prognosis
      of minor thoracic curve after isolated anterior fusion of the major lumbar curve
      has not been well described. PURPOSE: To define the prognosis of spontaneous
      thoracic curve correction after selective anterior fusion of the
      lumbar/thoracolumbar curve in idiopathic scoliosis. STUDY DESIGN: A retrospective
      cohort study on the prognosis of the minor curve after selective anterior
      correction and fusion of the lumbar/thoracolumbar curve in idiopathic scoliosis.
      PATIENT SAMPLE: Idiopathic lumbar scoliosis patients treated with anterior spinal
      fusion. OUTCOME MEASURES: The Scoliosis Research Society 22 questionnaire was
      used as an outcome measure at the final follow-up. METHODS: Twenty-eight patients
      were included in this study. Four patients were male, 24 patients were female,
      and average age at the time of surgery was 16 years. Mean follow-up was 48
      months. According to the Lenke Classification, 22 patients were 5CN, 5 were 5C-,
      and 1 was 5C+. All operations were performed in the same institution. Standing
      long posterior-anterior and lateral radiographs were taken just before surgery, 1
      week after surgery, and at final follow-up. RESULTS: The mean preoperative Cobb
      angle of the lumbar (major) curve was 53 degrees  (standard deviation [SD]=8.6)
      and that of the thoracic (minor) curve was 38.4 degrees  (SD=6.24). The lumbar
      and thoracic curves were corrected to 10 degrees  (SD=7.6) and 25 degrees 
      (SD=8.3) postoperatively and measured 17 degrees  (SD=10.6) and 27 degrees 
      (SD=7.7), respectively, at the last follow-up. There was a significant difference
      between the preoperative and postoperative measurements of the minor curves
      (p<.05). However, there was no significant difference between the early
      postoperative and the final follow-up measurements (p>.05). Regarding the overall
      sagittal balance, there was no significant difference between preoperative,
      early, and late postoperative measurements (p>.05). CONCLUSIONS: Selective
      anterior fusion of the major thoracolumbar/lumbar curve was an effective method
      for the treatment of Lenke Type 5C curves. Minor thoracic curves did not progress
      after selective fusion of thoracolumbar/lumbar curves in minimum 2-year follow
      up.

PMID- 24120147
TI  - Malignant solitary fibrous tumor of the lumbar spinal root mimicking schwannoma:
      a case report.
AB  - BACKGROUND CONTEXT: Malignant solitary fibrous tumors (SFTs) arising from the
      spinal cord are extremely rare and poorly understood mesenchymal neoplasms. To
      date, only one malignant SFT located in the spinal canal of the sacrum has been
      described, but none arising from the lumbar nerve root have been reported.
      Although most SFTs with benign histological features can be treated by complete
      surgical excision alone, malignant SFTs may require adjuvant therapy. However,
      systemic chemotherapy and radiotherapy have not been shown effective in patients
      with malignant SFTs. PURPOSE: To describe a patient with a malignant SFT arising
      from the lumbar nerve root. STUDY DESIGN: A case report and review of literature.
      METHODS: We describe the clinical course of the patient and the radiological and
      pathological findings of the tumor. The effect of systemic chemotherapy was
      evaluated and the relevant literature was reviewed. This work has no disclosure
      of funding and was approved by the Institutional Review Board of Gifu University.
      RESULTS: The tumor had been resected previously at another hospital, but it
      recurred and showed multiple metastatic lesions on both lungs within 3 months.
      Although the patient received systemic chemotherapy, both primary and metastatic
      lesions were found to be stable disease according to Response Evaluation Criteria
      in Solid Tumors. The patient died due to cachexia 6 months after her first visit.
      CONCLUSION: This patient presented with a highly unusual tumor. Even if a tumor
      is a dumbbell-shaped mass, similar to a neural tumor, SFT should be considered in
      the differential diagnosis.

PMID- 24120148
TI  - Removal of N-6-methyladenine by the nucleotide excision repair pathway triggers
      the repair of mismatches in yeast gap-repair intermediates.
AB  - Gap-repair assays have been an important tool for studying the genetic control of
      homologous recombination in yeast. Sequence analysis of recombination products
      derived when a gapped plasmid is diverged relative to the chromosomal repair
      template additionally has been used to infer structures of strand-exchange
      intermediates. In the absence of the canonical mismatch repair pathway,
      mismatches present in these intermediates are expected to persist and segregate
      at the next round of DNA replication. In a mismatch repair defective (mlh1Delta)
      background, however, we have observed that recombination-generated mismatches are
      often corrected to generate gene conversion or restoration events. In the
      analyses reported here, the source of the aberrant mismatch removal during gap
      repair was examined. We find that most mismatch removal is linked to the
      methylation status of the plasmid used in the gap-repair assay. Whereas more than
      half of Dam-methylated plasmids had patches of gene conversion and/or restoration
      interspersed with unrepaired mismatches, mismatch removal was observed in less
      than 10% of products obtained when un-methylated plasmids were used in
      transformation experiments. The methylation-linked removal of mismatches in
      recombination intermediates was due specifically to the nucleotide excision
      repair pathway, with such mismatch removal being partially counteracted by
      glycosylases of the base excision repair pathway. These data demonstrate that
      nucleotide excision repair activity is not limited to bulky, helix-distorting DNA
      lesions, but also targets removal of very modest perturbations in DNA structure.
      In addition to its effects on mismatch removal, methylation reduced the overall
      gap-repair efficiency, but this reduction was not affected by the status of
      excision repair pathways. Finally, gel purification of DNA prior to
      transformation reduced gap-repair efficiency four-fold in a nucleotide excision
      repair-defective background, indicating that the collateral introduction of UV
      damage can potentially compromise genetic interpretations. 

PMID- 24120149
TI  - [Impact of endocrine disrupting chemicals on birth outcomes].
AB  - BACKGROUND: Endocrine disruptors are ubiquitous chemicals contaminants in the
      environment, wildlife, and humans. Their adverse effects on reproduction are well
      documented. There is growing evidence that they can contribute to the current
      emergence of chronic diseases. OBJECTIVES: Our aim is to assess the relationships
      between endocrine disruptors and the neonatal health outcomes. METHODS: Two
      persons have independently reviewed Medline and Toxline databases about the
      following pollutants: bisphenol A, phthalates, parabens, brominated flame
      retardants and perfluorinated compounds. Only the human epidemiological studies,
      in general population with an abstract available, published between 2007 January
      the 1st and 2011 December the 31st, were analysed. The quality of each study was
      assessed with the Strobe score. RESULTS: Twenty-five out of 680 studies were
      included in the analysis. All pollutants were widely detected in maternal and new
      borns samples. Most of the studies have shown associations between bisphenol A,
      brominated flame retardants and perfluorinated compounds and lower birth weight.
      The effects on gestational age were less documented and have shown no clear
      connection. Results for phthalates were more ambiguous. Only one non-instructive
      study was found on parabens. DISCUSSION: Due to the inherent methological bias on
      endocrine disruptors research, further additional studies on environmental health
      must be investigated. It seems necessary to adopt preventive health measures
      first for vulnerable population.

PMID- 24120150
TI  - The role of hypoxia-inducible factors in renal fibrosis.

PMID- 24120151
TI  - Perception of spokespersons' performance and characteristics in crisis
      communication: experience of the 2003 severe acute respiratory syndrome outbreak
      in Taiwan.
AB  - BACKGROUND/PURPOSE: To explore perception of spokespersons' performance and
      characteristics in response to the 2003 severe acute respiratory syndrome (SARS)
      outbreak. METHODS: This study was conducted from March to July, 2005, using semi
      structured in-depth interviews to collect data. All interviews were audio
      recorded and transcribed verbatim. A qualitative content analysis was employed to
      analyze the transcribed data. Interviewees included media reporters, media
      supervisors, health and medical institution executives or spokespersons, and
      social observers. RESULTS: Altogether, 35 interviewees were recruited for in
      depth interviews, and the duration of the interview ranged from 1 hour to 2
      hours. Results revealed that the most important characteristics of health/medical
      institutions spokespersons are professional competence and good interaction with
      the media. In contrast, the most important behaviors they should avoid are
      concealing the truth and misreporting the truth. Three major flaws of
      spokespersons' performance were identified: they included poor understanding of
      media needs and landscape; blaming the media to cover up a mistake they made in
      an announcement; and lack of sufficient participation in decision-making or of
      authorization from the head of organization. CONCLUSION: Spokespersons of health
      and medical institutions play an important role in media relations during the
      crisis of a newly emerging infectious disease.

PMID- 24120142
TI  - The somatic genomic landscape of glioblastoma.
AB  - We describe the landscape of somatic genomic alterations based on
      multidimensional and comprehensive characterization of more than 500 glioblastoma
      tumors (GBMs). We identify several novel mutated genes as well as complex
      rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter
      mutations are shown to correlate with elevated mRNA expression, supporting a role
      in telomerase reactivation. Correlative analyses confirm that the survival
      advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT
      DNA methylation may be a predictive biomarker for treatment response only in
      classical subtype GBM. Integrative analysis of genomic and proteomic profiles
      challenges the notion of therapeutic inhibition of a pathway as an alternative to
      inhibition of the target itself. These data will facilitate the discovery of
      therapeutic and diagnostic target candidates, the validation of research and
      clinical observations and the generation of unanticipated hypotheses that can
      advance our molecular understanding of this lethal cancer. 

PMID- 24120152
TI  - Taiwanese Chinese translation and validation of the Quality of Life Questionnaire
      of the European Foundation for Osteoporosis 31 (QUALEFFO-31).
AB  - BACKGROUND/PURPOSE: Currently, Taiwanese Chinese version of a disease-specific
      health-related quality of life questionnaire for osteoporosis is not available.
      The purpose of this study was to translate and test the reliability and validity
      of the Taiwanese Chinese version of the Quality of Life Questionnaire of the
      European Foundation for Osteoporosis (QUALEFFO-31). METHODS: The QUALEFFO-31 was
      translated from the original English to Taiwanese Chinese. In this study, the
      translation procedure followed the guidelines described by Beaton et al. The
      intraclass correlation coefficient (ICC) was used to examine the test-retest
      reliability of the questionnaire. The internal consistency was assessed with
      Cronbach's alpha; Pearson's correlation was used to assess convergent and
      discriminant validity; the Mann Whitney U test was used to examine known group
      validity. RESULTS: The ICC for the test-retest reliability ranged from 0.77 to
      0.91; Cronbach's alpha for pain, physical function, and mental function domains
      were 0.85, 0.74, and 0.79, respectively. For the convergent and discriminant
      validity, the correlation coefficients of score of each item with score of pain
      domain and of other domains were 0.72-0.90 and 0.26-0.43, respectively; the
      physical domain, 0.19-0.68 and 0.00-0.45; the mental domain, 0.53-0.71 and 0.11
      0.38. CONCLUSION: The Taiwanese Chinese version of the QUALEFFO-31 is reliable
      and valid. We recommend this tool for evaluating participants with low bone mass
      in Taiwan. Further tests should be conducted to confirm the use of this
      questionnaire in clinical practice.

PMID- 24120153
TI  - Pulmonary function change in patients with Sauropus androgynus-related
      obstructive lung disease 15 years later.
AB  - BACKGROUND/PURPOSE: Little is understood about the clinical course and prognosis
      of patients with Sauropus androgynus-related obstructive lung disease. The aim of
      this study was to investigate their clinical manifestations and pulmonary
      function change 15 years after the acute episode. METHODS: A descriptive,
      observational study of patients with S androgynus-related obstructive lung
      disease, diagnosed 15 years ago, was conducted. We evaluated their pulmonary
      function and the Modified Medical Research Council (MMRC) dyspnea scale. Saint
      George's Respiratory Questionnaire (SGRQ) was also performed. Age- and forced
      expiratory volume in one second (FEV1)-matched chronic obstructive pulmonary
      disease (COPD) patients were used as a reference group for comparison of clinical
      manifestations. RESULTS: Twenty-nine of 49 patients, diagnosed at our hospital 15
      years ago, could be contacted. Four patients died and one patient was ventilator
      dependent. Sixteen patients were willing to come to our hospital to have
      pulmonary function and questionnaire evaluation. The FEV1 of these patients
      declined only 1.6 +/- 21.6 mL/year over a 15-year period. Meanwhile, the severity
      of their dyspnea and their health-related quality of life were better than age-
      and FEV1-matched COPD patients as shown by the MMRC dyspnea scale (1.4 +/- 0.8
      vs. 2.0 +/- 1.0; p = 0.037) and symptom domain of the SGRQ (32.6 +/- 18.4 vs.
      43.5 +/- 20.3; p = 0.006). CONCLUSION: After an acute deterioration, patients
      with S androgynus-related obstructive lung disease had a stationary pulmonary
      function over a period of 15 years, and their clinical manifestations were less
      severe than age- and FEV1-matched COPD patients. A further study with a larger
      sample size may be needed to confirm these findings.

PMID- 24120154
TI  - Mechanical stretch via transforming growth factor-beta1 activates microRNA-208a
      to regulate hypertrophy in cultured rat cardiac myocytes.
AB  - BACKGROUND/PURPOSE: MicroRNA-208a (miR208a) and mechanical stress play a key role
      in cardiac hypertrophy. The relationship between miR208a and mechanical stress in
      cultured cardiomyocytes has not been investigated. The molecular mechanisms
      underlying miR208a-induced hypertrophy of cardiomyocytes by mechanical stress is
      poorly understood. This study investigated whether miR208a is a critical
      regulator in cardiomyocyte hypertrophy under mechanical stretch. METHODS:
      Neonatal rat cardiomyocytes grown on a flexible membrane base were stretched at
      60 cycles/minute. MiR real-time quantitative assays were used to quantify miRs. A
      quantitative sandwich enzyme immunoassay technique was used to measure
      transforming growth factor-beta1 (TGF-beta1). A (3)H-proline incorporation assay
      was used to measure protein synthesis. RESULTS: Mechanical stretch significantly
      enhanced miR208a expression. Stretch significantly induced cardiomyocyte
      hypertrophic protein expression such as beta-myosin heavy chain (MHCbeta),
      thyroid hormone receptor-associated protein 100, myostatin, connexin 40, GATA4,
      and brain natriuretic peptide. MHCalpha was not induced by stretch.
      Overexpression of miR208a significantly increased MHCbeta protein expression
      while pretreatment with antagomir208a significantly attenuated MHCbeta protein
      expression induced by stretch and overexpression of miR208a. Mechanical stretch
      significantly increased the secretion of TGF-beta1 from cultured cardiomyocytes.
      Exogenous addition of TGF-beta1 recombinant protein significantly increased
      miR208a expression and pretreatment with TGF-beta1 antibody attenuated miR208a
      expression induced by stretch. Mechanical stretch and overexpression of miR208a
      increased protein synthesis while antagomir208a attenuated protein synthesis
      induced by stretch and overexpression of miR208a. CONCLUSION: Cyclic stretch
      enhances miR208a expression in cultured rat cardiomyocytes. MiR208a plays a role
      in stretch-induced cardiac hypertrophy. The stretch-induced miR208a is mediated
      by TGF-beta1.

PMID- 24120155
TI  - Experimental infection of dogs with Bartonella henselae and Bartonella vinsonii
      subsp. berkhoffii.
AB  - The lack of a suitable infection model remains an important obstacle for the
      pathophysiological understanding of Bartonella spp. The following pilot study was
      designed to determine whether cell culture-grown Bartonella henselae SA2 and
      Bartonella vinsonii subsp. berkhoffii genotype III would cause persistent
      bacteremia in dogs. Pre-inoculation screening established that two laboratory
      raised Golden retrievers were naturally-infected with Bartonella koehlerae.
      Despite prior infection, one dog each was inoculated subcutaneously with 5 *
      10(4)B. henselae (SA2 strain) or 3 * 10(4)B. vinsonii subsp. berkhoffii genotype
      III. Dogs were bled weekly for serological testing and culture using Bartonella
      alpha proteobacteria growth medium (BAPGM) diagnostic platform. Dog 1
      seroconverted to B. henselae and Dog 2 seroconverted to B. vinsonii subsp.
      berkhoffii genotype III. Throughout the study period, Bartonella spp. DNA was
      neither amplified nor isolated in ante-mortem BAPGM enrichment blood cultures. B.
      henselae SA2 was isolated from a postmortem bone marrow from Dog 1 and B.
      koehlerae DNA was amplified from postmortem lung from Dog 2 following BAPGM
      enrichment culture. Limitations include lack of uninfected controls, a
      potentially suboptimal B. vinsonii subsp. berkhoffii inoculum and a relatively
      short duration of study. We conclude that following intradermal infection,
      sequestration of Bartonella spp. in tissues may limit diagnostic detection of
      these bacteria in dog blood samples.

PMID- 24120156
TI  - Reply-nonimmune hydrops fetalis and lysosomal storage diseases.

PMID- 24120157
TI  - Nonimmune hydrops fetalis and lysosomal storage diseases.

PMID- 24120158
TI  - Feasibility of unattended home polysomnography in children with sleep-disordered
      breathing.
AB  - OBJECTIVE: To investigate the technical feasibility of unattended polysomnography
      (HPSG) for diagnosis of obstructive sleep apnea (OSA) in children. METHODS: A
      single-night HPSG was performed on children referred to the pediatric respiratory
      laboratory. Non-interpretable HPSGs were defined as: recordings with (i) loss of
      >=2 of the following channels: nasal flow, or thoraco-abdominal belts, or (ii)
      HPSG with less than 4 h of artifact-free recording time or (iii) less than 4 h
      SpO2 signal. RESULTS: Of n = 101 included HPSGs, n = 75 were ambulatory and n =
      26 in hospitalized subjects. Median (minimum-maximum) age was 2.8 (0-15.4) years.
      Interpretable and technically acceptable recordings were obtained in 94 subjects
      (93%). Only 7 recordings (4 at home versus 3 in hospitalized subjects, p-value =
      0.254) were classified as non-interpretable and had to be repeated. Artifact-free
      recording time was 461 (23-766)min. Complete artifact-free pulse oximetry signal
      was obtained in 14% of the included subjects. Neither age, gender, AHI, nor place
      of performance was significantly associated with the interpretability of
      recordings. DISCUSSION: HPSG showed a high rate of interpretability and technical
      acceptance. The high technical feasibility obtained by HPSG may help to improve
      simple screening tests for OSA in children.

PMID- 24120159
TI  - Intestinal Peyer's patch-immunomodulating glucomannans from rhizomes of
      Anemarrhena asphodeloides Bunge.
AB  - During screening for intestinal Peyer's patch-immunomodulating polysaccharides
      from plant resources including medicinal herbs, a potent modulating activity was
      observed in a crude polysaccharide fraction (AS-1) from the rhizome of
      Anemarrhena asphodeloides Bunge. Oral administration of AS-1 (100 mg/kg/day) to
      aged BALB/c mice enhanced productions of IL-10, IFN-gamma and IL-6 from Peyer's
      patch immunocompetent cells, and its oral administration to ovalbumin (OVA)-fed
      B10.A mice led to significant suppression on induction of OVA-specific IgE in
      systemic immune system. Further fractionation of the polysaccharides in the crude
      polysaccharide fraction, AS-1, yielded 4 polysaccharide fractions that were
      potently active, and contained glucomannans. Treatment of these polysaccharide
      fractions with endo-beta-D-(1->4)-mannanase significantly decreased their
      activities. Mannanase digestion of the active glucomannan gave both long and
      short hexosyl-oligosaccharides, whereas konjac glucomannan, which was inactive,
      released short oligosaccharides. Structural analysis indicates that the long
      oligosaccharides from the active glucomannan contain mannanase-resistant complex
      structure comprising beta-D-Man and beta-D-Glc.

PMID- 24120160
TI  - Examination of the transition of cultured neuronal cells from submerged to
      exposed using an environmental scanning electron microscope (ESEM).
AB  - Relatively few studies of fully hydrated live or fixed cultured animal cells
      viewed by environmental scanning electron microscopy (ESEM) have been published.
      In some cases there may have been some drying out of the cells. In this study the
      interface between water and cells is imaged as water is carefully evaporated to
      expose cells. Technical difficulties associated with the process, including
      inadvertent rewetting of cells are described. Suggestions are made for optimising
      operating parameters for viewing fully hydrated cultured cells by ESEM. The
      prospects for viewing live cultured cells are discussed. 

PMID- 24120161
TI  - Toward decentralized analysis of mercury (II) in real samples. A critical review
      on nanotechnology-based methodologies.
AB  - In recent years, it has increased the number of works focused on the development
      of novel nanoparticle-based sensors for mercury detection, mainly motivated by
      the need of low cost portable devices capable of giving fast and reliable
      analytical response, thus contributing to the analytical decentralization.
      Methodologies employing colorimetric, fluorometric, magnetic, and electrochemical
      output signals allowed reaching detection limits within the pM and nM ranges.
      Most of these developments proved their suitability in detecting and quantifying
      mercury (II) ions in synthetic solutions or spiked water samples. However, the
      state of art in these technologies is still behind the standard methods of
      mercury quantification, such as cold vapor atomic absorption spectrometry and
      inductively coupled plasma techniques, in terms of reliability and sensitivity.
      This is mainly because the response of nanoparticle-based sensors is highly
      affected by the sample matrix. The developed analytical nanosystems may fail in
      real samples because of the negative incidence of the ionic strength and the
      presence of exchangeable ligands. The aim of this review is to critically
      consider the recently published innovations in this area, and highlight the needs
      to include more realistic assays in future research in order to make these
      advances suitable for on-site analysis. 

PMID- 24120162
TI  - Recent advances in the development of single cell analysis--a review.
AB  - Development of techniques for the analysis of the content of individual cells
      represents an important direction in modern bioanalytical chemistry. While the
      analysis of chromosomes, organelles, or location of selected proteins has been
      traditionally the domain of microscopic techniques, the advances in miniaturized
      analytical systems bring new possibilities for separations and detections of
      molecules inside the individual cells including smaller molecules such as
      hormones or metabolites. It should be stressed that the field of single cell
      analysis is very broad, covering advanced optical, electrochemical and mass
      spectrometry instrumentation, sensor technology and separation techniques. The
      number of papers published on single cell analysis has reached several hundred in
      recent years. Thus a complete literature coverage is beyond the limits of a
      journal article. The following text provides a critical overview of some of the
      latest developments with the main focus on mass spectrometry, microseparation
      methods, electrophoresis in capillaries and microfluidic devices and respective
      detection techniques for performing single cell analyses. 

PMID- 24120163
TI  - Simultaneous detection of four biomarkers with one sensing surface based on redox
      probe tagging strategy.
AB  - In this paper, a simple and sensitive amperometric immunosensor for simultaneous
      detection of four biomarkers by using distinguishable redox-probes as signal tags
      was proposed for the first time. In sandwich immunoassay format, four kinds of
      capture antibodies (C-Ab) were immobilized by gold nanoparticles (AuNPs) electro
      deposited on the surface of glass carbon electrode (GCE); four kinds of detection
      antibodies (D-Ab) labeled with different redox probes (including anthraquinone 2
      carboxylic acid (Aq), thionine (Thi), ferrocenecarboxylic acid (Fc) and tris(2,2'
      bipyridine-4,4'-dicarboxylic acid) cobalt(III) (Co(bpy)3(3+))), were combined
      with 3,4,9,10-perylenetetracarboxylic acid (PTCA), poly(diallyldimethylammonium
      chloride) (PDDA) and AuNPs functionalized carbon nanotubes, and served as signal
      tracer. When four target antigens were present, differential pulse voltammetry
      (DPV) scan exhibited four well-resolved peaks, each peak indicated one antigen,
      and its intensity was quantitative correlational to the concentration of
      corresponding analyte. To verify the strategy, four biomarkers for diagnosis of
      colorectal carcinoma, including carcinoembryonic antigen (CEA), carbohydrate
      antigen (CA) 19-9 CA125, and CA242, were used as model analytes, the immunosensor
      exhibited high selectivity and sensitivity, and peak current displayed good
      linear relationship to logarithm concentration in the ranges from 0.016 to 15 ng
      mL(-1) for CEA; 0.008 to 10 ng mL(-1) for CA19-9; 0.012 to 12 ng mL(-1) for
      CA125; 0.010 to 10 ng mL(-1) for CA242, and low detection limits of 4.2, 2.8, 3.3
      and 3.8 pg mL(-1), respectively.

PMID- 24120164
TI  - A new method for stable lead isotope extraction from seawater.
AB  - A new technique for stable lead (Pb) isotope extraction from seawater is
      established using Toyopearl AF-Chelate 650M((r)) resin (Tosoh Bioscience LLC).
      This new method is advantageous because it is semi-automated and relatively fast;
      in addition it introduces a relatively low blank by minimizing the volume of
      chemicals used in the extraction. Subsequent analyses by HR ICP-MS have a good
      relative external precision (2sigma) of 3.50/00 for (206)Pb/(207)Pb, while
      analyses by MC-ICP-MS have a better relative external precision of 0.60/00.
      However, Pb sample concentrations limit MC-ICP-MS analyses to (206)Pb, (207)Pb,
      and (208)Pb. The method was validated by processing the common Pb isotope
      reference material NIST SRM-981 and several GEOTRACES intercalibration samples,
      followed by analyses by HR ICP-MS, all of which showed good agreement with
      previously reported values. 

PMID- 24120165
TI  - Proteomic platform for the identification of proteins in olive (Olea europaea)
      pulp.
AB  - The nutritional and cancer-protective properties of the oil extracted
      mechanically from the ripe fruits of Olea europaea trees are attracting
      constantly more attention worldwide. The preparation of high-quality protein
      samples from plant tissues for proteomic analysis poses many challenging
      problems. In this study we employed a proteomic platform based on two different
      extraction methods, SDS and CHAPS based protocols, followed by two precipitation
      protocols, TCA/acetone and MeOH precipitation, in order to increase the final
      number of identified proteins. The use of advanced MS techniques in combination
      with the Swissprot and NCBI Viridiplantae databases and TAIR10 Arabidopsis
      database allowed us to identify 1265 proteins, of which 22 belong to O. europaea.
      The application of this proteomic platform for protein extraction and
      identification will be useful also for other proteomic studies on recalcitrant
      plant/fruit tissues. 

PMID- 24120166
TI  - Water-compatible poly (hydroxyethyl methacrylate) polymer sorbent for
      miniaturized syringe assisted extraction of sulfonamides in milk.
AB  - A simple, convenient, and economic self-assembly miniaturized syringe assisted
      extraction (mini-SAE) using poly (hydroxyethyl methacrylate) polymer (PHEMA) as
      sorbent coupled with liquid chromatography was proposed for rapid screening of
      sulfadiazine (SD) and sulfamonomethoxine (SMM) in milk. The water-compatible
      PHEMA was synthesized by reversible addition-fragmentation chain transfer
      precipitation polymerization using trithiocarbonate as chain transfer agent and
      methanol-water system as reaction medium. The obtained PHEMA sorbent showed good
      affinity to sulfonamides and was successfully applied as a special sorbent for a
      mini-SAE device for simultaneous extraction and isolation of SD and SMM in milk
      samples. Under the optimum condition, good linearity was obtained in a range of
      7.0-700 ng g(-1) (r>=0.9995) and the average recoveries of SD and SMM at three
      spiked levels were ranged from 85.6 to 100.3% with the relative standard
      deviations (RSD) <=6.5%. The presented PHEMA-mini-SAE protocol could be
      potentially applied as an alternative tool for analyzing the residues of SAs in
      complicated biological samples.

PMID- 24120167
TI  - A microfluidic paper-based analytical device for rapid quantification of
      particulate chromium.
AB  - Occupational exposure to Cr is concerning because of its myriad of health
      effects. Assessing chromium exposure is also cost and resource intensive because
      the analysis typically uses sophisticated instrumental techniques like
      inductively coupled plasma-mass spectrometry (ICP-MS). Here, we report a novel,
      simple, inexpensive microfluidic paper-based analytical device (MUPAD) for
      measuring total Cr in airborne particulate matter. In the MUPAD, tetravalent
      cerium (Ce(IV)) was used in a pretreatment zone to oxidize all soluble Cr to
      Cr(VI). After elution to the detection zone, Cr(VI) reacts with 1,5
      diphenylcarbazide (1,5-DPC) forming 1,5-diphenylcarbazone (DPCO) and Cr(III). The
      resulting Cr(III) forms a distinct purple colored complex with the DPCO. As proof
      of-principle, particulate matter (PM) collected on a sample filter was analyzed
      with the MUPAD to quantify the mass of total Cr. A log-linear working range (0.23
      3.75 MUg; r(2)=0.998) between Cr and color intensity was obtained with a
      detection limit of 0.12 MUg. For validation, a certified reference containing
      multiple competing metals was analyzed. Quantitative agreement was obtained
      between known Cr levels in the sample and the Cr measured using the MUPAD.

PMID- 24120168
TI  - Focused-ion-beam-fabricated Au nanorods coupled with Ag nanoparticles used as
      surface-enhanced Raman scattering-active substrate for analyzing trace melamine
      constituents in solution.
AB  - A well-ordered Au-nanorod array with a controlled tip ring diameter (Au_NRsd) was
      fabricated using the focused ion beam method. Au_NRsd was then coupled with Ag
      nanoparticles (Ag NPs) to bridge the gaps among Au nanorods. The effect of
      surface-enhanced Raman scattering (SERS) on Au_NRsd and Ag NPs/Au_NRsd was
      particularly verified using crystal violet (CV) as the molecular probe. Raman
      intensity obtained from a characteristic peak of CV on Au_NRsd was estimated by
      an enhancement factor of ~10(7) in magnitude, which increased ~10(12) in
      magnitude for that on Ag NPs/Au_NRsd. A highly SERS-active Ag NPs/Au_NRsd was
      furthermore applied for the detection of melamine (MEL) at very low
      concentrations. Raman-active peaks of MEL (10(-3) to 10(-12)M) in water or milk
      solution upon Au_NRsd or Ag NPs/Au_NRsd were well distinguished. The peaks at 680
      and 702 cm(-1) for MEL molecules were found suitable to be used as the index for
      sensing low-concentration MEL in a varied solution, while that at 1051 cm(-1) was
      practical to interpret MEL molecules in water or milk solution bonded with Au
      (i.e., Au_NRsd) or Ag (i.e., Ag NPs/Au_NRsd) surface. At the interface of Ag
      NPs/Au_NRsd and MEL molecules in milk solution, a laser-induced electromagnetic
      field or hotspot effect was produced and competent to sense low-concentration MEL
      molecules interacting with Ag and Au surfaces. Accordingly, Ag NPs/Au_NRsd is
      very promising to be used as a fast and sensitive tool for screening MEL in
      complex matrices such as adulteration in e.g., food and pharmaceutical products.

PMID- 24120169
TI  - Sulfate-reducing bacteria detection based on the photocatalytic property of
      microbial synthesized ZnS nanoparticles.
AB  - This work presented a novel method for specific detection of sulfate-reducing
      bacteria (SRB) based on the photocatalytic property of ZnS nanoparticles. ZnS
      semiconductor nanoparticles were synthesized by taking advantage of the
      characteristic bacterial metabolite, sulfide, and then ZnS nanomaterials were
      used as photocatalyst for methylene blue (MB) photodegradation. As the amount of
      ZnS photocatalyst synthesized from microbe metabolized sulfide was affected by
      initial bacterial concentration before cultivation, the photodegradation ratio of
      MB was highly related with initial SRB concentration. Under the optimized
      conditions, a linear relationship between the MB photodegradation ratio and the
      logarithm of SRB concentration was observed in the range of 1.0*10(3)-1.0*10(8)
      cfu mL(-1). Besides, this proposed method showed excellent specificity for SRB
      detection. To the best of our knowledge, this is the first example of using the
      photocatalytic property of microbial synthesized ZnS for bacterial detection.

PMID- 24120170
TI  - Hypochlorous acid turn-on boron dipyrromethene probe based on oxidation of methyl
      phenyl sulfide.
AB  - A boron dipyrromethene (BODIPY)-based fluorometric probe, HCS, has been
      successfully developed for the highly sensitive and selective detection of
      hypochlorous acid (HOCl). The probe is based on the specific HOCl-promoted
      oxidation of methyl phenyl sulfide. The reaction is accompanied by a 160-fold
      increase in the fluorescent quantum yield (from 0.003 to 0.480). The fluorescent
      turn-on mechanism is accomplished by suppression of photoinduced electron
      transfer (PET) from the methyl phenyl sulfide group to BODIPY. The fluorescence
      intensity of the reaction between HOCl and HCS shows a good linearity in the HOCl
      concentration range 1-10 MUM. The detection limit is 23.7 nM (S/N=3). In
      addition, confocal fluorescence microscopy imaging using RAW264.7 macrophages
      demonstrates that the HCS probe could be an efficient fluorescent detector for
      HOCl in living cells.

PMID- 24120171
TI  - Novel B,O-chelated fluorescent probe for nitric oxide imaging in Raw 264.7
      macrophages and onion tissues.
AB  - A novel fluorescent probe based on B,O-chelated dipyrromethene chromophore in far
      visible and near-infrared spectral region (600-900 nm), boron chelated 8-(3,4
      diaminophenyl)-3,5-bis(2-hydroxyphenyl)-4-bora-3a,4a-diaza-s-indancene (BOPB),
      has been first developed for nitric oxide (NO) imaging. BOPB, a turn-on
      fluorescent probe, can react with NO rapidly under physiological condition. The
      reaction product of BOPB with NO, BOPB-T, emits bright red fluorescence at 643 nm
      when excited at 622 nm. Meanwhile, BOPB-T displays high fluorescent quantum yield
      of 0.21 and good photostability. The selectivity for NO over other reactive
      oxygen/nitrogen species and ascorbic acid has been investigated and BOPB has good
      specificity for the detection of NO. MTT assay shows that the toxicity of BOPB
      (below 10 MUM) to living cells can be neglected. Based on these investigations,
      BOPB has been used for NO imaging in Raw 264.7 cells and onion tissues.
      Meanwhile, mechanical injury to onion tissues results in a brighter fluorescence
      around the wound, which indicates that more NO has been produced in plant tissues
      in response to external stimuli. Our studies illustrate that BOPB has advantages
      of high sensitivity, low background interference and little photo damage on
      fluorescence imaging of NO.

PMID- 24120172
TI  - Fast and effective paper based sensor for self-diagnosis of bacterial vaginosis.
AB  - In this contribution we present a sensitive colorimetric bioactive paper
      fabricated to determine sialidase-related diseases like bacterial vaginosis (BV)
      in a one-step and dry format spot assay with fast response and good storage
      stability. The paper was prepared by three simple steps. The first step involves
      preparation of poly(ethyleneimine) (PEI) microcapsules, the second step is to
      incubate positively charged microcapsules in negatively charged 5-bromo-4-chloro
      3-indolyl-a-D-N-acetylneuraminic acid (BCIN) solution, a color enhancer nitro
      blue tetrazolium (NBT), and in the third step, paper was fabricated by
      incorporating incubated microcapsules into paper pulp. This paper changes color
      from white to dark purple in the presence of sialidase in as little as 6min, and
      color could be enhanced with increased length of reaction time. In this reaction
      system, BCIN was the substrate for sialidase, NBT was the color enhancer, and PEI
      microcapsules acted as catalyst. The loading efficiency of BCIN was about 22.2%,
      and filtered BCIN solution could be reused for the next fabrication.

PMID- 24120173
TI  - Hydroxyethylammonium monosubstituted cyclodextrin as chiral selector for
      capillary electrophoresis.
AB  - A novel cationic cyclodextrin, mono-6(A)-(2-hydroxyethyl-1-ammonium)-6(A)-beta
      cyclodextrin chloride (HEtAMCD) has been successfully synthesized and applied as
      chiral selector in capillary electrophoresis. The NMR study revealed this chiral
      selector has three recognition sites: beta-CD, ammonium cation and hydroxy group
      in the sidearm to contribute three corresponding driving forces including
      inclusion complexation, electrostatic interaction and hydrogen bonding. The
      effect of buffer pH and HEtAMCD concentration (2.5-10 mM) on enantioselectivity,
      chiral resolution as well as effective mobility of analytes was investigated.
      This elegantly designed CD exhibits outstanding enantioselectivities toward the
      studied hydroxyl acids and ampholytic racemates in CE with the aid of extra
      hydrogen bonding. Under optimum pH 6.0, chiral resolutions over 5 can be readily
      obtained for hydroxy acids with CD concentration below 5mM. The comparison study
      between HEtAMCD and our earlier reported ammonium CDs indicates the
      hydroxyethylammonium group of HEtAMCD significantly increased the
      enantioselective capability.

PMID- 24120174
TI  - Capillary zone electrophoresis and capillary electrophoresis-mass spectrometry
      for analyzing qualitative and quantitative variations in therapeutic albumin.
AB  - The present study describes a reproducible and quantitative capillary zone
      electrophoresis (CZE) method, which leads to the separation of nine forms
      (native, oxidized and glycated) of human serum albumin (HSA). In an attempt to
      identify the different species separated by this CZE method, the capillary
      electrophoresis was coupled to mass spectrometry using a sheath liquid interface,
      an optimized capillary coating and a suitable CE running buffer. CE-MS analyses
      confirmed the heterogeneity of albumin preparation and revealed new truncated and
      modified forms such as Advanced Glycation End products (AGEs). Assignment of the
      CZE peaks was carried out using specific antibodies, carboxypeptidase A or sample
      reduction before or during the CE separation. Thus, five HSA forms were
      unambiguously identified. Using this CZE method several albumin batches produced
      by slightly different fractionation ways could be discriminated. Furthermore,
      analyses of HSA preparations marketed by five pharmaceutical industries revealed
      that two therapeutic albumins, including that marketed by LFB, contained the
      highest proportion of native form and lower levels of oxidized forms. 

PMID- 24120175
TI  - Facile synthesis of calcium silicate hydrate using sodium dodecyl sulfate as a
      surfactant assisted by ultrasonic irradiation.
AB  - Calcium silicate hydrate (CSH) consisting of nanosheets has been successfully
      synthesized assisted by a tip ultrasonic irradiation (UI) method using calcium
      nitrate (Ca(NO3).4H2O), sodium silicate (Na2SiO3.9H2O) and sodium dodecyl sulfate
      (SDS) in water. Systematic studies found that reaction time of ultrasonic
      irradiation and concentrations of surfactant (SDS) in the system were important
      factors to control the crystallite size and morphologies. The products were
      characterized by X-ray power diffraction (XRD), field emission scanning electron
      microscopy (FESEM) and Fourier transform infrared spectrometry (FTIR). The size
      strain plot (SSP) method was used to study the individual contributions of
      crystallite sizes and lattice strain on the peak broadening of the CSH. These
      characterization techniques revealed the successful formation of a crystalline
      phase with an average crystallite size of about 13 nm and nanosheet morphology at
      a reaction time of 10 min UI with 0.2 g SDS in solvent which were found to be
      optimum time and concentrations of SDS for the synthesis of CSH powders.

PMID- 24120176
TI  - Gastrointestinal parasite control during prepuberty improves mammary parenchyma
      development in Holstein heifers.
AB  - Parasitism during development impairs normal growth and delays the onset of
      puberty through altered hormone profiles, including insulin-like growth factor
      one (IGF-1). As mammary gland development during prepuberty is strongly dependent
      on IGF-1, we determined if antiparasitic treatment during this stage of growth
      improved mammary gland development. One group of Holstein heifers was treated
      monthly, rotationally with antiparasitic drugs from birth to 70 weeks of age, a
      second group was untreated. Treated heifer calves had between 56% and 65% less
      EPG counts than untreated ones. Presence of Ostertagia, Cooperia, Haemonchus and
      Trichostrongylus was demonstrated. Treatment effectively advanced the onset of
      puberty and increased IGF-1 levels. At 20, 30, 40 and 70 weeks of age biopsies
      from the mammary gland were taken and histological sections were prepared and
      stained with hematoxylin-eosin. Pictures were analyzed to compare parenchyma area
      in relation to total mammary tissue between groups. Mammary samples from treated
      heifers had higher ratios of parenchyma/total area than untreated ones. As
      mammary development during prepuberty is crucial for mammary performance during
      lactation, these results add new evidence to the importance of gastrointestinal
      parasite control in heifers. 

PMID- 24120177
TI  - A preliminary investigation of farm-level risk factors for cattle condemnation at
      the slaughterhouse: a case-control study on French farms.
AB  - The financial impact of condemnation for farmers and the importance of efficiency
      in the meat inspection process to guarantee food safety are well known.
      Identifying farm-level risk factors for condemnation are useful in order to find
      a way for farmers to potentially reduce their condemnation rates and to build a
      risk-based farm classification for veterinary services to target both meat
      inspection and farms inspections. To our knowledge, this has not yet been done,
      probably due to a lack of available meat inspection data. A preliminary
      investigation was performed through a case-control study on 36 French farms, from
      a dairy production region to identify farm-level risk factors for high
      condemnation rates (i.e. more than 45% of cattle with at least one portion of the
      carcass condemned). Multivariable exact logistic regression was performed to take
      into account the small sample size. The final model identified two significant
      risk factors. The odds of having a high condemnation rate was at least twice as
      greater for farmers who did not adhere to the quality charter of an international
      retailer and was significantly higher when the most qualified worker on the farm
      had a degree in agriculture. This latter effect was unexpected and is reviewed in
      the discussion section. The protective effect of the quality charter could be
      explained by the annual control of farms performed to guarantee compliance with
      good farming practices in the adhering farms. It led us to believe that
      compliance with well known good farming practices could be a way for farmers to
      reduce their condemnation rates. This study is a preliminary investigation
      performed on a small sample size of farms that were mainly dairy farms. It is a
      first step for further investigations that need to be done on this topic at a
      larger scale to fill the current lack of knowledge. 

PMID- 24120178
TI  - Characteristics, prognosis, and outcomes of cutaneous ischemia and gangrene in
      systemic necrotizing vasculitides: a retrospective multicenter study.
AB  - OBJECTIVES: To describe the prevalence, characteristics, and outcome of cutaneous
      ischemia, and whether it can occur in systemic necrotizing vasculitides (SNVs),
      i.e., polyarteritis nodosa, granulomatosis with polyangiitis, and eosinophilic
      granulomatosis with polyangiitis and microscopic polyangiitis. METHODS: We
      conducted a retrospective analysis of all patients with SNV who were included in
      the French Vasculitis Study Group cohort database between March 1963 and
      September 2007. We compared characteristics and outcomes for patients with and
      without cutaneous ischemia (digital necrosis and/or isolated necrotic cutaneous
      ulcers). RESULTS: Among the 1304 patients with a diagnosis of SNVs, 40 (3.1%) had
      digital necrosis and 25 (1.9%) had isolated necrotic cutaneous ulcers, with an
      equal distribution among SNVs. Presence of cutaneous ischemia was associated with
      past and/or current smoking [odds ratio (OR), 1.73; 95% confidence interval (95%
      CI), 1.02-2.95] and history of coronary artery disease (2.40; 1.01-6.00), as well
      as with other cutaneous manifestations (6.54; 3.21-8.67), gastrointestinal tract
      perforations (4.29; 1.41-13.07), and arthralgias (1.84; 1.10-3.07) during
      diagnosis. Ten patients with digital necrosis underwent extremity amputation, but
      no patient with isolated necrotic cutaneous ulcers (p = 0.007) underwent it.
      Smoking was the main risk factor of amputation (OR, 9.1; 1.7-48.9). At a mean
      follow-up of 10 years, cutaneous ischemia was identified as an independent
      predictor of vasculitis relapse (hazard ratio, 1.47; 95% CI, 1.05-2.05) and all
      cause death (1.66; 1.01-2.74). CONCLUSIONS: Cutaneous ischemia is a rare
      manifestation of SNVs but is associated with an increased risk of relapse and
      mortality. Tobacco use is associated with amputation, which emphasizes the
      importance of managing conventional cardiovascular risk factors in SNV patients.

PMID- 24120180
TI  - Recent trends in incidence of five common cancers in 26 European countries since
      1988: Analysis of the European Cancer Observatory.
AB  - BACKGROUND: Individual country- and cancer site-specific studies suggest that the
      age-adjusted incidence of many common cancers has increased in European
      populations over the past two decades. To quantify the extent of these trends and
      the recent burden of cancer, here we present a comprehensive overview of trends
      in population-based incidence of the five common cancers across Europe derived
      from a new web-based portal of the European cancer registries. METHODS: Data on
      incidence for cancers of the colon and rectum, prostate, breast, corpus uteri and
      stomach diagnosed from 1988 to 2008 were obtained from the European Cancer
      Observatory for cancer registries from 26 countries. Annual age-standardised
      incidence rates and average annual percentage changes were calculated. RESULTS:
      Incidence of four common cancers in eastern and central European countries
      (prostate, postmenopausal breast, corpus uteri and colorectum) started to
      approach levels in northern and western Europe, where rates were already high in
      the past but levelled off in some countries in recent years. Decreases in stomach
      cancer incidence were seen in all countries. DISCUSSION: Increasing trends in
      incidence of the most common cancers, except stomach cancer, are bad news to
      public health but can largely be explained by well-known changes in society in
      the past decades. Thus, current and future efforts in primary cancer prevention
      should not only remain focussed on the further reduction of smoking but engage in
      the long-term efforts to retain healthy lifestyles, especially avoiding excess
      weight through balanced diets and regular physical exercise.

PMID- 24120179
TI  - Hypocaloric diet supplemented with probiotic cheese improves body mass index and
      blood pressure indices of obese hypertensive patients--a randomized double-blind
      placebo-controlled pilot study.
AB  - BACKGROUND: Gut lactobacilli can affect the metabolic functions of healthy
      humans. We tested whether a 1500 kcal/d diet supplemented with cheese containing
      the probiotic Lactobacillus plantarum TENSIA (Deutsche Sammlung fur
      Mikroorganismen, DSM 21380) could reduce some symptoms of metabolic syndrome in
      Russian adults with obesity and hypertension. METHODS: In this 3-week,
      randomized, double-blind, placebo-controlled, parallel pilot study, 25 subjects
      ingested probiotic cheese and 15 ingested control cheese. Fifty grams of each
      cheese provided 175 kcal of energy. Blood pressure (BP), anthropometric
      characteristics, markers of liver and kidney function, metabolic indices (plasma
      glucose, lipids, and cholesterol), and urine polyamines were measured. Counts of
      fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular
      methods. The data were analyzed by t-test for independent samples and Spearman's
      partial correlation analysis. RESULTS: The probiotic L. plantarum TENSIA was
      present in variable amounts (529.6 +/- 232.5 gene copies) in 16/25 (64%) study
      subjects. Body mass index (BMI) was significantly reduced (p = 0.031) in the
      probiotic cheese group versus the control cheese group. The changes in BMI were
      closely associated with the water content of the body (r = 0.570, p = 0.0007)
      when adjusted for sex and age. Higher values of intestinal lactobacilli after
      probiotic cheese consumption were associated with higher BMI (r = 0.383, p =
      0.0305) and urinary putrescine content (r = 0.475, p = 0.006). In patients
      simultaneously treated with BP-lowering drugs, similar reductions of BP were
      observed in both groups. A positive association was detected between TENSIA
      colonization and the extent of change of morning diastolic BP (r = 0.617, p =
      0.0248) and a trend toward lower values of morning systolic BP (r = -0.527, p =
      0.0640) at the end of the study after adjusting for BMI, age, and sex.
      CONCLUSION: In a pilot study of obese hypertensive patients, a hypocaloric diet
      supplemented with a probiotic cheese helps to reduce BMI and arterial BP values,
      recognized symptoms of metabolic syndrome.

PMID- 24120181
TI  - Neuromechanical gait adaptations in women with joint hypermobility--an
      exploratory study.
AB  - BACKGROUND: Joint hypermobility is known to be associated with joint and muscle
      pain, joint instability and osteoarthritis. Previous work suggested that those
      individuals present an altered neuromuscular behavior during activities such as
      level walking. Therefore, the aim of this study was to explore the differences in
      ground reaction forces, temporal parameters and muscle activation patterns during
      gait between normomobile and hypermobile women, including symptomatic and
      asymptomatic hypermobile individuals. METHODS: A total of 195 women were included
      in this cross-sectional study, including 67 normomobile (mean 24.8 [SD 5.4]
      years) and 128 hypermobile (mean 25.8 [SD 5.4] years), of which 56 were further
      classified as symptomatic and 47 as asymptomatic. The remaining 25 subjects could
      not be further classified. Ground reaction forces and muscle activation from six
      leg muscles were measured while the subjects walked at a self-selected speed on
      an instrumented walkway. Temporal parameters were derived from ground reaction
      forces and a foot accelerometer. The normomobile and hypermobile groups were
      compared using independent samples t-tests, whereas the normomobile, symptomatic
      and asymptomatic hypermobile groups were compared using one-way ANOVAs with Tukey
      post-hoc tests (significance level=0.05). FINDINGS: Swing phase duration was
      higher among hypermobile (P=0.005) and symptomatic hypermobile (P=0.018) compared
      to normomobile women. The vastus medialis (P=0.049) and lateralis (P=0.030) and
      medial gastrocnemius (P=0.011) muscles showed higher mean activation levels
      during stance in the hypermobile compared to the normomobile group.
      INTERPRETATION: Hypermobile women might alter their gait pattern in order to
      stabilize their knee joint.

PMID- 24120182
TI  - One-year temporal stability and predictive and incremental validity of the body,
      eating, and exercise comparison orientation measure (BEECOM) among college women.
AB  - This study examined the one-year temporal stability and the predictive and
      incremental validity of the Body, Eating, and Exercise Comparison Measure
      (BEECOM) in a sample of 237 college women who completed study measures at two
      time points about one year apart. One-year temporal stability was high for the
      BEECOM total and subscale (i.e., Body, Eating, and Exercise Comparison
      Orientation) scores. Additionally, the BEECOM exhibited predictive validity in
      that it accounted for variance in body dissatisfaction and eating disorder
      symptomatology one year later. These findings held even after controlling for
      body mass index and existing measures of social comparison orientation. However,
      results regarding the incremental validity of the BEECOM, or its ability to
      predict change in these constructs over time, were more mixed. Overall, this
      study demonstrated additional psychometric properties of the BEECOM among college
      women, further establishing the usefulness of this measure for more
      comprehensively assessing eating disorder-related social comparison. 

PMID- 24120183
TI  - Use of the translabyrinthine approach to repair congenital spontaneous
      cerebrospinal fluid leakage in five Chinese patients with Mondini dysplasia.
AB  - OBJECTIVES: To introduce a more effective surgical technique for the repair of
      spontaneous incurable cerebrospinal fluid (CSF) leakage (CSF otorrhea). METHODS:
      The cases of five Chinese patients with Mondini dysplasia and CSF leakage were
      reviewed. All patients presented with rhinorrhea or otorrhea from childhood and
      recurrent meningitis attacks. CSF leakage was repaired surgically using the
      translabyrinthine approach. RESULTS: Facial paralysis occurred in the first two
      patients, but was cured 2 months later. The other three patients recovered well
      and had no facial paralysis or complication. CSF leakage did not recur in any
      patient after follow-up periods of 0.5-3 years. CONCLUSION: Mondini dysplasia
      with CSF leakage is rare. Adequate diagnosis and treatment are required to avoid
      life-threatening complications, such as meningitis. We recommend the
      translabyrinthine approach as an alternative surgical technique that reduces
      recurrence.

PMID- 24120184
TI  - Comparison of Z and R3 antigen expression and of genes encoding other antigenic
      markers in invasive human and bovine Streptococcus agalactiae strains from
      Norway.
AB  - Streptococcus agalactiae (GBS) may cause a variety of infectious diseases in
      humans caused by human GBS and mastitis in cattle caused by bovine GBS. Over the
      last few years molecular testing has provided evidence that human and bovine GBS
      have evolved along diverse phylogenetic lines. In the present study 173 invasive
      human GBS strains and 52 invasive bovine strains were tested for altogether 18
      strain-variable and surface-localized antigenic markers including all 10 capsular
      polysaccharides (CPS) and proteins including Cbeta, the alpha-like proteins, R3
      and the recently described Z1 and Z2 antigens. PCR was used to detect encoding
      genes and antibody-based methods to detect expression of antigens. Thirteen of
      the 18 markers were detected in isolates of both strain categories. Seven of the
      ten CPS antigens were detected in both groups with types III and V predominating
      in the human GBS strains, types IV and V in the bovine isolates. Z1, Z2 and/or R3
      expression and the genes encoding Cbeta, Calpha, Alp1, Alp2/3 or R4 (Rib) were
      detected in both groups. Protein antigen-CPS associations well known for human
      strains were essentially the same in the bovine isolates. The results show that
      in spite of evolution along different lines, human and bovine GBS share a variety
      of surface-exposed antigenic markers, substantiating close relationship between
      the two GBS subpopulations. 

PMID- 24120185
TI  - Parents' experiences of pediatric palliative care and the impact on long-term
      parental grief.
AB  - CONTEXT: Approximately 25% of children diagnosed with cancer eventually die.
      Losing a child puts parents at increased risk for developing psychological
      problems. OBJECTIVES: To explore parents' perceptions of the interaction with
      health care professionals (communication, continuity of care, and parental
      involvement) and symptom management during the pediatric palliative phase, and to
      investigate the influence on long-term grief in parents who lost a child to
      cancer. METHODS: A total of 89 parents of 57 children who died of cancer between
      2000 and 2004 participated in this retrospective cross-sectional study by
      completing a set of questionnaires measuring grief (Inventory of Traumatic
      Grief), parents' perceptions of the interaction with health care professionals
      (communication, continuity of care, and parental involvement), and symptom
      management during the palliative phase. Care was assessed on a five point Likert
      scale (1=disagree and 5=agree). RESULTS: Parents highly rated communication
      (4.6+/-0.6), continuity of care (4.3+/-0.6), and parental involvement (4.6+/-0.7)
      during the palliative phase. Parents' most often reported physical and
      psychological symptoms of their child during the palliative phase were fatigue
      (75%), pain (74%), anxiety to be alone (52%), and anger (48%). Higher ratings of
      parents on communication (beta=-9.08, P=0.03) and continuity of care (beta=
      11.74, P=0.01) were associated with lower levels of long-term parental grief. The
      severity of the child's dyspnea (beta=2.96, P=0.05), anxiety to be alone
      (beta=4.52, P<0.01), anxiety about the future (beta=5.02, P<0.01), anger
      (beta=4.90, P<0.01), and uncontrolled pain (beta=6.60, P<0.01) were associated
      with higher levels of long-term parental grief. Multivariate models combining the
      interaction with health care professionals and symptom management showed a
      significant influence of both aspects on long-term parental grief. CONCLUSION:
      Both interaction with health care professionals, especially communication and
      continuity of care, and symptom management in children dying of cancer are
      associated with long-term parental grief levels.

PMID- 24120186
TI  - How to cope with an ageing population.

PMID- 24120187
TI  - Opening eyes to prevent blindness.

PMID- 24120188
TI  - The continuing haemorrhage of UK general practice.

PMID- 24120189
TI  - Universal health coverage and social determinants of health.

PMID- 24120191
TI  - Tom Walley: leading light of HTA in the UK.

PMID- 24120192
TI  - Global kidney disease.

PMID- 24120193
TI  - Global kidney disease.

PMID- 24120194
TI  - Global kidney disease - Authors' reply.

PMID- 24120195
TI  - Global kidney disease.

PMID- 24120196
TI  - Health and research in Pakistan.

PMID- 24120197
TI  - Health and research in Pakistan.

PMID- 24120198
TI  - Health and research in Pakistan.

PMID- 24120199
TI  - Health and research in Pakistan - Authors' reply.

PMID- 24120200
TI  - Reconsidering the Declaration of Helsinki.

PMID- 24120201
TI  - Reconsidering the Declaration of Helsinki.

PMID- 24120203
TI  - Section 136 and police custody.

PMID- 24120202
TI  - Reconsidering the Declaration of Helsinki - Author' s reply.

PMID- 24120204
TI  - Health Technology Assessment in the UK.
AB  - In this Review, we discuss the UK's Health Technology Assessment programme, which
      is 20 years old in 2013. We situate the programme in the context of the UK
      landscape for evidence-based medicine, including in relation to the National
      Institute for Health and Care Excellence and as guidance to the National Health
      Service. We identify features that might be of value to other health systems as
      they confront the challenges of rapid innovation and rising costs. We use
      examples of recent studies to show the strengths and weaknesses of the programme.

PMID- 24120205
TI  - Improving forensic investigation for polonium poisoning.

PMID- 24120206
TI  - Dry cough.

PMID- 24120207
TI  - Intrathoracic giant pleural lipoma: case report and review of the literature.
AB  - This report describes a giant pleural lipoma that arose from the pleura of the
      7th anterior intercostal space and occupied approximately 75% of the right
      pleural cavity in a 49-year-old woman. The tumor was completely excised by right
      thoracotomy. The complete histopathological investigation showed pleural lipoma,
      and we made a review of literature.

PMID- 24120208
TI  - Tibial plateau fractures: reproducibility of three classifications (Schatzker,
      AO, Duparc) and a revised Duparc classification.
AB  - INTRODUCTION: Since the reproducibility of the Schatzker and AO tibial plateau
      fracture classification systems has already been assessed, the goal of this study
      was to evaluate the Duparc classification system and compare it to the other two.
      HYPOTHESES: CT scan is better than X-rays for analyzing and classifying tibial
      plateau fractures. The Duparc classification system is more effective than the
      other two systems but could be improved by adding elements of each. MATERIALS AND
      METHODS: Six observers analyzed images from 50 fractures and then classified
      them. Each fracture was evaluated on X-rays. Two weeks later, these same
      fractures were evaluated on X-rays and CT scans. The same process was repeated
      four weeks later. The Kappa coefficient (kappa) was used to measure agreement and
      contingency tables were built. RESULTS: The interobserver reproducibility for the
      X-ray analysis was poor for the Duparc and AO classifications (kappaDuparc=0.365;
      kappaAO=0.357) and average for the Schatzker classification
      (kappaSchatzker=0.404). The reproducibility was improved overall when CT scans
      were also analyzed (kappaDuparc=0.474; kappaAO=0.479; kappaSchatzker=0.476). A
      significantly greater number of fractures could not be classified in the
      Schatzker system than in the others (14.3% versus 2% for Duparc and 7.33% for
      AO). Review of the contingency tables revealed that the Schatzker and AO
      classification systems did not take certain fracture types into account. Seventy
      one percent (71%) of the lateral unicondylar split fractures were found to be
      combined fractures when CT scan analysis was added. DISCUSSION: Our results
      showed CT scan to be better at analyzing and classifying fractures. We also found
      the Duparc classification to be advantageous because it allowed more fractures to
      be classified than in other classification systems, while having similar
      reproducibility. Based on our study findings, the Duparc classification was
      revised by adding elements of the other two. We propose using the modified Duparc
      classification system to analyze tibial plateau fractures going forward. LEVEL OF
      EVIDENCE: Level IV. Retrospective study.

PMID- 24120209
TI  - [Quality of information in the process of informed consent for anesthesia].
AB  - OBJECTIVES: To assess the quality of the information that patients receive in the
      informed consent document signed prior to surgery. MATERIAL AND METHODS: Cross
      sectional study of a sample of cancer patients admitted for surgery at the
      University Hospital San Cecilio of Granada in 2011. After checking the inclusion
      criteria and obtaining their consent, demographic data were collected and
      procedure data, and a questionnaire "ad hoc" to assess the quality and
      comprehensiveness of the information provided in the informed consent. RESULTS:
      150 patients were studied. The majority (109 over 150) said they had received
      sufficient information, in appropriate language, and had the opportunity to ask
      questions, but only 44.7% correctly answered three or more issues related to
      anesthesia. University education level, knowledge of the intervention,
      information about the anesthesia problems and appropriate language were
      associated. CONCLUSIONS: Although systematic informed consent was performed, half
      of the patients did not comprehend the anesthesia risks. Variables primarily
      related to the information received were associated with the quality of the
      response, but not with patient characteristics.

PMID- 24120210
TI  - First FCTC case in the Netherlands.

PMID- 24120211
TI  - Prosthodontic rehabilitation of a patient diagnosed with multiple idiopathic root
      resorption.
AB  - A female college student was referred by her general dentist for evaluation of
      the interproximal caries-like lesions discovered during her biannual visit. The
      lesions were determined to result from external resorption of unknown origin.
      After the most affected teeth had been extracted and the other teeth were
      restored after periodontal surgery, an interim partial removable dental
      prosthesis was placed. Two months later, the resorption pattern had proliferated
      to the rest of her dentition, thus revising the treatment plan to involve full
      mouth extractions and to place immediate maxillary and mandibular complete
      removable dental prostheses. Subsequently, 6 titanium dental implants were placed
      in each arch, and, after healing, opposing metal ceramic screw-retained fixed
      dental prostheses were inserted. 

PMID- 24120212
TI  - Quantification of left ventricular performance in different heart failure
      phenotypes by comprehensive ergometry stress echocardiography.
AB  - BACKGROUND: We evaluated the left ventricular (LV) performance in patients with
      heart failure and preserved ejection fraction (HFPEF) during exercise as compared
      to those with heart failure and reduced ejection fraction (HFREF) and healthy
      subjects. METHODS: All subjects received echocardiographic (Vivid7, GE
      Healthcare) examination with symptom-limited exercise testing on a semi-recumbent
      and tilting bicycle ergometer (Lode BV, Netherlands). The exercise images for 2
      dimensional (2D) speckle tracking were acquired with heart rate of 90-100 bpm,
      while exercise images for tissue Doppler imaging (TDI) and M-mode
      echocardiography were stored with attainment of >85% of maximal age-predicted
      heart rate. RESULTS: Stress echocardiographic examinations were performed in 40
      HFPEF (aged 65 +/- 9 years; 53% male), 40 HFREF (aged 62 +/- 9 years; 90% male)
      and 30 normal controls (aged 56 +/- 5 years; 33% male). Trends of progressive
      decline in 2D global longitudinal, circumferential and radial strains (GLS, GCS
      and GRS); TDI septal s' and Sm; and M-mode mitral annular plane systolic
      excursion (MAPSE) were observed from control, HFPEF to HFREF groups (p<0.05 for
      all). LV twist was preserved in HFPEF but reduced in HFREF patients as compared
      to normal controls (p<0.05). Diastolic function measured by TDI septal e', Em and
      septal E/e' progressively decreased from controls, HFPEF to HFREF patients (all
      p<0.05). Stroke volumes and cardiac indices (LVSI & LVCI) were preserved in HFPEF
      but deteriorated in HFREF than controls. CONCLUSIONS: This study provides the
      reference values of LV performance during exercise in HFPEF and knowledge about
      these changes provide important insights for future clinical studies.

PMID- 24120213
TI  - Misrepresentation of vital status follow-up: challenging the integrity of the
      PLATO trial and the claimed mortality benefit of ticagrelor versus clopidogrel.
AB  - CONTEXT: Ticagrelor, a novel, reversible, and oral P2Y12 receptor antagonist, was
      claimed to reduce all-cause mortality compared to clopidogrel in the PLATO trial.
      OBJECTIVE: We sought to ascertain vital status follow-up for clopidogrel and
      ticagrelor to determine if any discrepancy existed by reviewing data from the FDA
      Complete Response Review. RESULTS: The FDA Complete Response Review indicated
      misrepresentation of vital status follow-up by the sponsor's presenter at the
      Cardiovascular and Renal Drugs Advisory Committee. Instead of five patients with
      missing vital status follow-up, the FDA primary efficacy reviewer indicated that
      there was a minimum of 106 patients. Additionally and more concerning was the
      fact that significantly more patients on ticagrelor (3.1%, n = 289 patients) had
      incomplete vital status follow-up versus clopidogrel (2.6%, n = 242 patients, p =
      0.04 for the difference). CONCLUSIONS: The Advisory Committee that voted in favor
      to approve ticagrelor was given misrepresented data, which may have affected the
      approval of ticagrelor. The fact that significantly more patients on ticagrelor
      had incomplete vital status follow-up versus clopidogrel challenges the claimed
      mortality benefit of ticagrelor and the approval of the PLATO trial.

PMID- 24120214
TI  - Aortic stiffness and hypotension episodes are associated with impaired cognitive
      function in older subjects with subjective complaints of memory loss.
AB  - OBJECTIVE: Though CV risk factors and markers of arterial aging are recognized
      risky for cognition, no study has simultaneously investigated the impact of
      multiple cardiac, arterial (large and small vessels), and hemodynamic parameters
      on cognitive function in older subjects. METHODS: Two hundred eighty older
      subjects with subjective complaints of memory loss and no previous stroke (mean
      age 78.3 +/- 6.3 years) were studied. Global cognitive function was evaluated
      with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined
      as a MMSE < 21. We measured: traditional CV risk factors; aorta stiffness (Pulse
      Wave Velocity, PWV); LV mass; presence of WML at neuroimaging; episodes of
      hypotension (SBP <100 mmHg during 24 h Ambulatory Blood Pressure Monitoring).
      RESULTS: In both cross-sectional and longitudinal analyses PWV, WML, and episodes
      of hypotension were significantly associated with poorer cognitive function
      controlling for age, sex, education, depression, traditional CV risk factors, and
      medications. LV mass was no longer associated with cognition in multiple
      regression. Older subjects with stiffer arteries or episodes of hypotension
      presented a 4-fold and an 11-fold, respectively, greater odds for progression
      from normal cognitive function to cognitive impairment. A synergistic effect
      between PWV, WML, and hypotension was observed: the occurrence of any two of PWV,
      WML, or hypotension was accompanied by lower MMSE; in the presence of all three
      factors, a further significant decline in cognitive function was observed.
      INTERPRETATION: Systemic hemodynamic parameters (higher PWV and hypotension)
      together with cerebral microvascular damage (WML) are significantly associated
      with poorer cognitive function and may identify older subjects with subjective
      complaints of memory loss at higher risk of cognitive decline.

PMID- 24120215
TI  - Improvement of myocardial function and perfusion after successful percutaneous
      revascularization in patients with chronic total coronary occlusion.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) for chronic total occlusion
      (CTO) of a coronary artery can provide benefits in terms of myocardial function
      and survival but the procedure is complex and the success rate is relatively low.
      To assess these benefits, myocardial function, ischemia and viability should be
      clearly determined by means of a reliable diagnostic test. This study aimed to
      assess ventricular function and myocardial ischemia before and after PCI for CTO
      using cardiac magnetic resonance (CMR). NYHA functional class was also assessed
      before and after PCI. METHODS AND RESULTS: CMR studies were performed in 43
      consecutive patients (7 females; aged 64 +/- 9.6 y.o.) with CTO scheduled for PCI
      and repeated 6 months post-PCI. PCI was successful in 33 (77%) of them. In this
      group CMR had shown inducible perfusion defects in 26 (79%) before PCI, while
      they were observed in 10 (30%) post-PCI CMR study (p < 0.001). The number of
      segments showing inducible perfusion defect (3.4 +/- 2 prevs. 2.9 +/- 4.5 post
      PCI, p = 0.002) was significantly reduced in this group. Regional contractile
      function of segments showing viability also improved significantly in the group
      with successful CTO PCI compared to the group with an unsuccessful procedure.
      NYHA functional class for angina also improved in patients with successful
      revascularization while it remained unchanged in the group with unsuccessful
      procedures. CONCLUSIONS: A successful CTO PCI leads to a reduction in inducible
      myocardial ischemia and to an improvement in regional wall motion, which results
      in clinical improvement.

PMID- 24120217
TI  - Assessment of perioperative antimicrobial prophylaxis using ATC/DDD methodology.
AB  - OBJECTIVES: In the light of international experience and guidelines and in order
      to improve the quality of perioperative antimicrobial prophylaxis (PAP), various
      hospitals have set up their own multidisciplinary healthcare teams and have
      evaluated the density of PAP through close supervision and interventions. The aim
      of the present study was to compare the density, quality, and cost of PAP before
      and after an intervention implemented at our hospital in order to increase the
      quality of PAP. METHODS: PAP was monitored using a form prepared in line with the
      international guidelines, which was completed by the infection control nurse
      under the supervision of the infectious diseases specialist. In order to reduce
      the frequent errors in our PAP procedures, an intervention was implemented, and
      the period before this intervention (January-April 2011) was compared with the
      post-intervention period 1 year later (January-April 2012). The density of PAP
      was calculated according to the Anatomical Therapeutic Chemical
      classification/defined daily dose (ATC/DDD) methodology. RESULTS: A total of 2398
      patients received PAP during this period. The most frequently used antibiotic
      before and after the intervention was cefazolin. Its use further increased after
      the intervention (p<0.001). After the intervention, the ratio of the correct
      timing of the first antibiotic dose increased from 91.7% to 99.0% (p<0.001),
      while the excessively long administration of PAP was reduced from 77.0% to 44.7%
      (p<0.001). The ratio of full compliance with the guidelines increased from 15.5%
      to 40.2% (p<0.001) and the rate of surgical site infections dropped from 18.5% to
      12.0%. The density of antibiotic use dropped from 305.7 DDD/100 procedures=3.1
      DDD/procedure to 162.1 DDD/100 procedures=1.6 DDD/procedure. CONCLUSION: The
      quality of PAP may be improved through better compliance with healthcare
      guidelines, close supervision, and training activities. Also, surgical site
      infections and the cost of PAP may be reduced through more appropriate antibiotic
      use, thus contributing to the national healthcare budget.

PMID- 24120218
TI  - Difficult choices we must make when studying complex patients.

PMID- 24120216
TI  - Early changes in hepatic function among HIV-tuberculosis patients treated with
      nevirapine or efavirenz along with rifampin-based anti-tuberculosis therapy.
AB  - OBJECTIVES: To describe the longitudinal changes in hepatic function among HIV
      infected tuberculosis (TB) patients receiving once-daily nevirapine (NVP)- or
      efavirenz (EFV)-based antiretroviral treatment (ART) along with rifampin
      containing anti-TB treatment. METHODS: This was a nested study within a
      randomized clinical trial, taking place between May 2006 and June 2008 at the
      National Institute for Research in Tuberculosis, Chennai, India. Antiretroviral
      naive HIV-infected TB patients were initiated on an intermittent short-course
      regimen and randomized to receive didanosine and lamivudine with either NVP (400
      mg) or EFV (600 mg) once-daily. Blood was analyzed for alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (SAP), and
      bilirubin at baseline, at ART initiation, fortnightly after ART initiation until
      2 months, then monthly until 6 months and 6-monthly thereafter. RESULTS: Of the
      168 patients included (79% men, median CD4 count 93 cells/mm3, median viral load
      242,000 copies/ml), 104 were on EFV-based ART and 64 on NVP-based ART. There was
      a small but statistically significant elevation in ALT and SAP at 2 weeks and AST
      at 6 weeks after ART initiation. The proportion of patients with rate-limiting
      toxicity of liver enzymes was small. None had treatment terminated because of
      hepatotoxicity. CONCLUSION: Hepatotoxicity is not a major concern when HIV
      infected TB patients, with normal baseline liver function initiate treatment for
      both infections simultaneously.

PMID- 24120219
TI  - Cationic eluate pretreatment for automated synthesis of [68Ga]CPCR4.2.
AB  - Fostered by the clinical success of sst-ligands, the development and evaluation
      of (68)Ga-labeled peptides have become a very active field in radiopharmaceutical
      chemistry. Consequently, various new peptide tracers have been developed, e.g.
      [(68)Ga]CPCR4.2 for in vivo imaging of solid and haematological tumors or
      [(68)Ga]TRAP(RGD)3 for imaging of alpha(v)beta3 integrin expression. As a
      consequence of different matrices (TiO2, SnO2, polymers) exploited in commercial
      (68)Ge/(68)Ga-generators, HCl of different concentrations (0.05...1.0 M) is used
      to obtain (68)Ga as starting material for automated syntheses. We have developed
      a purification method which reduces the eluate volume and adjusts the HCl
      concentration. The method may potentially allow standardization of the eluate
      composition of different commercial generators prior to labeling. Recently, a
      cationic purification process has been reported which allows the pre-fixation of
      (68)Ga on a Varian SCX cation exchange cartridge and subsequent elution of (68)Ga
      with acidified NaCl solutions. As part of the development of ready-to-use
      cassettes for the automated production of (68)Ga-CPCR4.2 using a SCINTOMICS GRP
      module and an iThemba Labs generator that is eluted with 0.6...1.0 M HCl, we
      tested and compared the (68)Ga-trapping efficiency of various commercial
      available cation exchange cartridges, the efficiency of subsequent (68)Ga-elution
      from these cartridges by means of various protocols and the influence of these
      variations on the labeling efficiency of [(68)Ga]CPCR4.2, [(68)Ga]TRAP(RGD)3 and
      [(68)Ga]DOTATATE/[(68)Ga]DOTANOC. Finally, we transferred the optimized method to
      the automated, cassette based synthesis of [(68)Ga]CPCR4.2 and the aforementioned
      peptides. From seven tested cation exchange cartridges, Chromafix PS-H(+) gave
      the best extraction results (>95%). Moreover, we observed that acidified
      solutions of 5 M NaCl or 2.5 M CaCl2 can be used for efficient cartridge elution.
      Using a disposable cGMP-compliant cassette system, we obtained [(68)Ga]CPCR4.2 in
      80% decay-corrected yield and >99% purity. These data were confirmed by the
      production of [(68)Ga]DOTATATE, [(68)Ga]DOTANOC and [(68)Ga]TRAP(RGD)3 on the
      otherwise identical cassette system.

PMID- 24120220
TI  - [18F]Altanserin and small animal PET: impact of multidrug efflux transporters on
      ligand brain uptake and subsequent quantification of 5-HT2A receptor densities in
      the rat brain.
AB  - INTRODUCTION: The selective 5-hydroxytryptamine type 2a receptor (5-HT(2A)R)
      radiotracer [(18)F]altanserin is a promising ligand for in vivo brain imaging in
      rodents. However, [(18)F]altanserin is a substrate of P-glycoprotein (P-gp) in
      rats. Its applicability might therefore be constrained by both a differential
      expression of P-gp under pathological conditions, e.g. epilepsy, and its
      relatively low cerebral uptake. The aim of the present study was therefore
      twofold: (i) to investigate whether inhibition of multidrug transporters (MDT) is
      suitable to enhance the cerebral uptake of [(18)F]altanserin in vivo and (ii) to
      test different pharmacokinetic, particularly reference tissue-based models for
      exact quantification of 5-HT(2A)R densities in the rat brain. METHODS: Eighteen
      Sprague-Dawley rats, either treated with the MDT inhibitor cyclosporine A (CsA,
      50 mg/kg, n=8) or vehicle (n=10) underwent 180-min PET scans with arterial blood
      sampling. Kinetic analyses of tissue time-activity curves (TACs) were performed
      to validate invasive and non-invasive pharmacokinetic models. RESULTS: CsA
      application lead to a two- to threefold increase of [(18)F]altanserin uptake in
      different brain regions and showed a trend toward higher binding potentials
      (BP(ND)) of the radioligand. CONCLUSIONS: MDT inhibition led to an increased
      cerebral uptake of [(18)F]altanserin but did not improve the reliability of
      BP(ND) as a non-invasive estimate of 5-HT(2A)R. This finding is most probable
      caused by the heterogeneous distribution of P-gp in the rat brain and its
      incomplete blockade in the reference region (cerebellum). Differential MDT
      expressions in experimental animal models or pathological conditions are
      therefore likely to influence the applicability of imaging protocols and have to
      be carefully evaluated.

PMID- 24120221
TI  - The risk of recurrent thromboembolic disorders in patients with unprovoked venous
      thromboembolism: new scenarios and opportunities.
AB  - The risk of recurrent thromboembolic disorders in the 10-year period following an
      episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the
      rate being higher in patients with primary deep venous thrombosis (DVT) than in
      those with primary pulmonary embolism (PE). The clinical presentation with
      primary PE increases by more than three times the risk of a new PE episode over
      that with isolated DVT. Baseline parameters that increase this risk are the
      proximal location of DVT, obesity, old age and male sex, whereas the role of
      thrombophilia is controversial. An increasing role is played by post-baseline
      parameters such as the ultrasound assessment of residual vein thrombosis and the
      determination of D-dimer. While the latest international guidelines suggest
      indefinite anticoagulation for most patients with the first episode of unprovoked
      VTE, new scenarios are being offered by the identification of risk stratification
      models and by strategies that have the potential to help identify patients in
      whom anticoagulation can be safely discontinued, such as those that incorporate
      the assessment of D-dimer and residual vein thrombosis. New opportunities are
      being offered by low-dose aspirin, which has recently been reported to decrease
      by more than 30% the risk of recurrent events without increasing the bleeding
      risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which
      are likely to induce fewer haemorrhagic complications than vitamin K antagonists
      while preserving at least the same effectiveness, do not require laboratory
      monitoring, and can be used immediately after the thrombotic episode. 

PMID- 24120222
TI  - [Mucinous tumour in a mature ovarian teratoma: An unusual presentation of
      pseudomyxoma peritonei].

PMID- 24120223
TI  - 'It's your problem, not mine': does competence have anything to do with desire
      and aspiration to self-direct?
AB  - The current disability policy paradigm operating across all states in Australia
      is self-direction. This central movement is closely linked to preparations for a
      National Disability Insurance Scheme called DisabilityCare. We provide one
      perspective in relation to self-direction in Australia including assumptions
      about aspirations to self-direct and the limited research evidence base that is
      available even though anecdotally self-direction practices have been occurring
      for many years. We conclude that by developing a funding platform, such as
      DisabilityCare, that empowers people with a disability to make decisions about
      their own fundamental needs and the fulfilment of them, it will lead to a society
      that supports people to access and achieve a 'typical' and desired life. 

PMID- 24120225
TI  - The role of aortic wall CT attenuation measurements for the diagnosis of acute
      aortic syndromes.
AB  - OBJECTIVES: To determine if measurements of aortic wall attenuation can improve
      the CT diagnosis of acute aortic syndromes. METHODS: CT reports from a ten year
      period were searched for acute aortic syndromes (AAS). Studies with both an
      unenhanced and a contrast enhanced (CTA) series that had resulted in the
      diagnosis of intramural hematoma (IMH) were reviewed. Diagnoses were confirmed by
      medical records. The attenuation of aortic wall abnormalities was measured. The
      observed attenuation threshold was validated using studies from 39 new subjects
      with a variety of aortic conditions. RESULTS: The term "aortic dissection" was
      identified in 1206, and IMH in 124 patients' reports. IMH was confirmed in 31
      patients, 21 of whom had both unenhanced and contrast enhanced images. All 21 had
      pathologic CTA findings, and no CTA with IMH was normal. Attenuation of the
      aortic wall was greater than 45 HUs on the CTA images in all patients with IMH.
      When this threshold was applied to the new group, sensitivity for diagnosing AAS
      was 100% (19/19), and specificity 94% (16/17). Addition of unenhanced images did
      not improve accuracy. CONCLUSIONS: Measurements of aortic wall attenuation in CTA
      have a high negative predictive value for the diagnosis of acute aortic
      syndromes.

PMID- 24120226
TI  - Therapeutic embolization of high-flow priapism 1 year follow up with color
      Doppler sonography.
AB  - OBJECTIVE: The aim of this study was to evaluate the use of color Doppler
      sonography (CDS) for the diagnosis of high-flow priapism and the treatment of
      cavernosal arterial fistula via super-selective arterial embolization. METHODS
      AND MATERIALS: We reviewed eight cases of high-flow priapism with cavernosal
      arterial fistula, from 2005 to 2011. All of the patients were diagnosed with a
      high-flow priapism and unilateral artery fistula via CDS. Conventional treatments
      for the eight cases were unsuccessful, and the patients were then treated through
      super-selective embolization. Diagnostic angiograms of the internal iliac artery
      showed a fistula on one side of the cavernosal artery, thus confirming the CDS
      images. We compared hemodynamic parameters including the peak systolic velocity,
      end diastolic velocity the resistance index of the pathological cavernosal artery
      and intracavernosal pressure in all patients before and after treatment using t
      test. The efficacy of super-selective embolization and the erectile function of
      all patients were evaluated at a follow-up time of 12 months. RESULTS: All
      patients were successfully treated and angiography showed that the fistulas
      disappeared after treatment. Additionally significant differences were found in
      the peak systolic velocity, the end diastolic velocity, the resistance index and
      intracavernosal pressure between pre-treatment and post-treatment (P<0.05). At 5
      days post-treatment, only one case relapses had occurred. Seven cases displayed
      restored erectile function and only one case exhibited erectile dysfunction.
      CONCLUSION: Color Doppler sonography is a highly sensitive method for the
      examination of high-flow priapism, and super-selective embolization is a safe and
      effective treatment for cavernosal arterial fistula.

PMID- 24120224
TI  - Effect of age and dialysis vintage on obesity paradox in long-term hemodialysis
      patients.
AB  - BACKGROUND: In contrast to the general population, higher body mass index (BMI)
      is associated with greater survival in patients receiving hemodialysis (HD;
      "obesity paradox"). We hypothesized that this paradoxical association between BMI
      and death may be modified by age and dialysis vintage. STUDY DESIGN:
      Retrospective observational study using a large HD patient cohort. SETTING &
      PARTICIPANTS: 123,383 maintenance HD patients treated in DaVita dialysis clinics
      between July 1, 2001, and June 30, 2006, with follow-up through September 30,
      2009. PREDICTORS: Age, dialysis vintage, and time-averaged BMI. Time-averaged BMI
      was divided into 6 subgroups; <18.5, 18.5-<23.0, 23.0-<25.0, 25.0-<30.0, 30.0
      <35.0, and >=35.0kg/m(2). BMI category of 23-<25kg/m(2) was used as the reference
      category. OUTCOMES: All-cause, cardiovascular, and infection-related mortality.
      RESULTS: Mean BMI of study participants was 27+/-7kg/m(2). Time-averaged BMI was
      <18.5 and >=35kg/m(2) in 5% and 11% of patients, respectively. With progressively
      higher time-averaged BMI, there was progressively lower all-cause,
      cardiovascular, and infection-related mortality in patients younger than 65
      years. In those 65 years or older, even though overweight/obese patients had
      lower mortality compared with underweight/normal-weight patients, sequential
      increases in time-averaged BMI > 25kg/m(2) added no additional benefit. Based on
      dialysis vintage, incident HD patients had greater all-cause and cardiovascular
      survival benefit with a higher time-averaged BMI compared with the longer term HD
      patients. LIMITATIONS: Causality cannot be determined, and residual confounding
      cannot be excluded given the observational study design. CONCLUSIONS: Higher BMI
      is associated with lower death risk across all age and dialysis vintage groups.
      This benefit is more pronounced in incident HD patients and those younger than 65
      years. Given the robustness of the survival advantage of higher BMI, examining
      interventions to maintain or even increase dry weight in HD patients irrespective
      of age and vintage are warranted.

PMID- 24120227
TI  - Sedimentary PBDEs in urban areas of tropical Asian countries.
AB  - Polybrominated diphenyl ethers (PBDEs) were measured in surface sediment samples
      collected from urban canals or rivers in Lao PDR, Cambodia, Vietnam, India,
      Indonesia, Thailand, the Philippines, Malaysia and Japan. The total PBDE
      concentrations in the sediments ranged from 0.83 to 3140 ng/g dry wt. BDE-209 was
      predominant, ranging from 43% to 97% of total PBDEs, followed by nona-BDEs and
      some detectable concentrations of BDEs 47, 49, 99, 100, 153, 154 and 183.
      Sedimentary PBDE levels in Malaysia, Cambodia, the Philippines and Thailand were
      generally higher than those reported for highly industrialized countries. Spatial
      distribution of PBDEs indicated that inland sources may impact coastal areas. The
      presence of BDE congeners which are not contained in technical mixtures and the
      higher proportions of nona-BDEs relative to BDE-209 in the sediments were
      identified as indicators of debromination. BDE-209 was possibly debrominated
      under anaerobic conditions in some of the sediment samples.

PMID- 24120228
TI  - Effects of anthropogenic metallic contamination on cholinesterases of Gambusia
      holbrooki.
AB  - Metal contamination causes multiple biological dysfunctions, including impairment
      of key physiological functions by targeting enzymes. This feature is a matter of
      concern, since it may imply significant disturbances in energy allocation,
      behaviour, reproduction, and survival. Inhibition of the cholinesterase (ChE)
      activity of aquatic organisms by metals has been described, and systematically
      used in biomonitoring studies as effect criterion of environmental exposure to
      these compounds. The present paper addresses the feasibility of using ChE
      inhibition to quantify the adverse acute and chronic effects of metals (copper,
      zinc, lead, and cadmium) on nervous tissue of Gambusia holbrooki. With the
      exception of acute exposure to copper, ChE activity was not significantly
      impaired. The meanings of the reported findings are further discussed, aiming at
      a more comprehensive use of this biomarker in environmental assessment. Based on
      the obtained results, the role of ChE inhibition in environmental metal
      contamination scenarios should be questioned or even discarded. 

PMID- 24120230
TI  - Abstracts of the 17th Annual Scientific Meeting of the Japanese Heart Failure
      Society. November 28-30, 2013.

PMID- 24120231
TI  - Aneurysm of the internal carotid artery after minor trauma.
AB  - We report a rare case of posttraumatic aneurysm of the internal carotid artery.
      The aneurysm was surgically removed, followed by a simple postoperative course.
      Such lesions should be highly suspected in cases of penetration into the
      retroangulomandibular neck region. 

PMID- 24120232
TI  - Bicycle testing as an alternative diagnostic tool in patients suspected of
      intermittent claudication.
AB  - BACKGROUND: The ankle-brachial index (ABI) obtained after a treadmill challenge
      is often used to confirm the diagnosis of intermittent claudication (IC).
      However, some patients fail treadmill testing due to (temporary) orthopedic or
      neurologic comorbidity or fear of falling. The aim of this study was to evaluate
      the role of bicycle testing as an alternative for treadmill testing. It was
      hypothesized that ABIs obtained after bicycle tests were not different compared
      with values after standard treadmill testing. METHODS: In this validation study,
      newly diagnosed IC patients (Rutherford 1-3) underwent a standard treadmill test
      (TT, "gold standard") and two bicycle protocols, one with a continuous resistance
      submaximal character (submaximal bicycle test, SBT) and a second with an
      incremental ramp form having a maximal character (maximal bicycle test, MBT).
      ABIs of both legs were obtained before and twice after each of these three
      different exercise tests. Healthy individuals matched for age and gender served
      as controls. RESULTS: The study population consisted of 32 patients (68 +/- 11
      years, 21 men). ABIs of each leg (n = 64) obtained after TT correlated
      significantly with values obtained after either bicycle test (TT vs. SBT: r =
      0.90, P < 0.001; TT vs. MBT: r = 0.88, P < 0.001). Drops in ABI after both types
      of exercise were significantly correlated (TT vs. SBT: r = 0.66, P < 0.001; TT
      vs. MBT: r = 0.32, P < 0.01). A 98% sensitivity and 86% specificity for diagnosis
      of IC was observed after the SBT. After the MBT, these values were 98% and 43%,
      respectively. Healthy controls (n = 13) demonstrated ABI values >0.9 after
      cycling in all tests. CONCLUSIONS: Both submaximal and a maximal bicycle tests
      may serve as alternative noninvasive tools for detecting intermittent
      claudication. Bicycle tests can potentially be used for patients unable to
      perform a treadmill test.

PMID- 24120233
TI  - Surgical treatment of an aneurysm of a distal branch of the renal artery.
AB  - Aneurysms of the renal artery and its branches are rare, but are associated with
      significant morbimortality due to the absence of clinical symptoms and
      hemorrhagic risk in the event of rupture. We report the case of a patient with an
      aneurysm of a distal branch of the right renal artery that measured 25 mm in
      diameter. The diagnosis and localization were obtained using selective
      arteriography. Treatment consisted of resection of the aneurysmal sac associated
      with closure with a saphenous vein patch rather than an endovascular treatment in
      order to preserve the nephronic capital. Right renal parenchymatous
      vascularization was satisfactory on arterial echo-Doppler and angioscanner
      assessment at 1 year. 

PMID- 24120229
TI  - How to fix a broken clock.
AB  - Fortunate are those who rise out of bed to greet the morning light well rested
      with the energy and enthusiasm to drive a productive day. Others, however, depend
      on hypnotics for sleep and require stimulants to awaken lethargic bodies.
      Sleep/wake disruption is a common occurrence in healthy individuals throughout
      their lifespan and is also a comorbid condition to many diseases
      (neurodegenerative) and psychiatric disorders (depression and bipolar). There is
      growing concern that chronic disruption of the sleep/wake cycle contributes to
      more serious conditions including diabetes (type 2), cardiovascular disease, and
      cancer. A poorly functioning circadian system resulting in misalignments in the
      timing of clocks throughout the body may be at the root of the problem for many
      people. In this article we discuss environmental (light therapy) and lifestyle
      changes (scheduled meals, exercise, and sleep) as interventions to help fix a
      broken clock. We also discuss the challenges and potential for future development
      of pharmacological treatments to manipulate this key biological system. 

PMID- 24120234
TI  - Low-density lipoprotein levels and not mutation status predict intima-media
      thickness in familial hypercholesterolemia.
AB  - BACKGROUND: Intima-media thickness (IMT) is a well-described marker of
      cardiovascular disease. In this study we aim to determine whether low-density
      lipoprotein (LDL) levels and disease-related mutation status can predict IMT in
      patients with severe familial hypercholesterolemia (FH) referred for or on LDL
      apheresis. METHODS: Genetic screening, lipid profile testing, and IMT
      measurements were performed on a series of 33 severe FH patients (19 homozygous)
      on LDL apheresis treatments (LDL 447 +/- 151 mg/dL, age range 6-60 years). Data
      were then compared with literature IMT-LDL data for normal subjects, mild FH
      patients, and severe FH patients (18, 41, and 6 studies, respectively). RESULTS:
      Age-adjusted IMT was linearly related to LDL levels over a wide range of values
      (<500 mg/dL), except for the severe FH no-apheresis cohort. Alternatively, our
      severe FH population (mostly on apheresis) did follow the mild FH/control age
      adjusted IMT-LDL relation. CONCLUSIONS: In severe FH, measuring LDL levels is
      more predictive of increased IMT than genetic screening.

PMID- 24120235
TI  - The Virtual histology In CaroTids Observational RegistrY (VICTORY) study: a
      European prospective registry to assess the feasibility and safety of
      intravascular ultrasound and virtual histology during carotid interventions.
AB  - BACKGROUND: Carotid occlusive disease is the most common determinant of
      thromboembolic stroke. However, limited insights in vivo into the pathophysiology
      and pathology of carotid plaques are available. We designed a prospective
      multicenter registry to appraise the safety and feasibility of intravascular
      ultrasound (IVUS) and IVUS-virtual histology (IVUS-VH) imaging before and
      immediately after carotid stenting. METHODS: Symptomatic and asymptomatic
      patients scheduled for carotid stenting were included. IVUS-VH pullbacks were
      performed before and after stenting. Angiographic, IVUS and IVUS-VH analyses were
      performed. The primary objective was to appraise feasibility and safety of IVUS
      VH, and secondary objectives were to correlate plaque composition and plaque type
      derived from IVUS-VH with acute and 30-day complications. RESULTS: A total of 119
      patients were enrolled. IVUS-VH could be performed in all cases (100%), with
      additional runs after completion of the stenting procedure in 85%. Most plaques
      were stable by IVUS-VH, with vulnerable ones at minimum lumen area in 7%.
      Conversely, vulnerable plaques were significantly more common elsewhere in the
      internal carotid artery (ICA, 24% of patients, p<0.001). Acute and 30-day adverse
      events were uncommon (2 strokes, 1 transient ischemic attack), with no
      significant association between these and IVUS-VH features. CONCLUSIONS: IVUS and
      IVUS-VH examinations during carotid interventions are feasible and safe, and
      provide important insights on qualitative and quantitative compositions of
      carotid plaques. Whether carotid IVUS-VH can predict clinical events remains
      uncertain, awaiting long-term follow-up of the VICTORY study and additional
      clinical trials.

PMID- 24120236
TI  - Sheep farmer opinions on the current and future role of veterinarians in flock
      health management on sheep farms: a qualitative study.
AB  - A 2009 UK Government report on veterinary expertise in food animal production
      highlighted that there was insufficient herd health expertise among veterinarians
      and lack of appropriate business models to deliver veterinary services to the
      livestock sector. Approximately two thirds of sheep farmers only contact their
      veterinarian for emergencies and one fifth have all year round contact. The aim
      of the current study was to understand sheep farmers' perception, the current and
      future role of veterinarians in flock health management using qualitative
      methodology. The eligibility criteria were male farmers with a flock size of at
      least 200 adult sheep. Seven focus groups of farmers (n=45) stratified by three
      regions and two age groups (<=50 and >50) were conducted. Thematic analysis of
      the discussions indicated that most farmers considered and used their
      veterinarian as a fire-fighter, whilst other advice was gathered free of charge
      when the veterinarian was on the farm for other reasons (typically seeing cattle)
      or by telephone. A small group of farmers were using their veterinarian or a
      sheep consultant proactively with regular contact and found this financially
      beneficial. Farmers indicated that the key barriers to using a veterinarian
      proactively were inconsistent service, high turnover of veterinarians, lack of
      expertise of sheep farming among veterinarians and concern about independence of
      advice. Although economics was also mentioned as a key barrier to using
      veterinarians more proactively, most farmers did not know where they gained and
      lost income from their flock; there was heavy reliance on the single farm payment
      scheme (SPS) and very few farmers kept records from which they could investigate
      where there were inefficiencies in production. Overall sheep farmers considered
      sheep farming complex and that each farm was unique and that they themselves were
      the experts to manage their flock. We conclude that there is an impasse:
      veterinarians might need to provide consistency and wide expertise beyond
      knowledge of disease and a model of how flock planning would be financially
      beneficial but until sheep farmers keep production records flock health planning
      cannot be rigorous and the financial benefits cannot be evaluated. Given the
      reliance on SPS by farmers an alternative model would be to require farmers to
      keep production records to comply with SPS. This might lead to flock health
      planning being adopted at a faster rate and so develop the UK sheep industry and
      make it more environmentally sustainable by reducing waste from disease and low
      productivity. 

PMID- 24120237
TI  - Hemostatic derangement in dengue hemorrhagic fever.
AB  - Dengue hemorrhagic fever (DHF) is a more severe manifestation of dengue virus
      infection. Patients with DHF exhibit abnormal hematological indices, including
      high hematocrit, low white blood cells, low neutrophils, high lymphocytes,
      increased atypical lymphocytes, low platelets, slightly prolonged activated
      partial thromboplastin time, prothrombin time, and thrombin time. Abnormal
      platelet functions manifest as impaired platelet aggregation to ADP, and
      concurrent increases in plasma thromboglobulin and platelet factor 4 levels are
      also seen. Variable reductions in the activities of coagulation factors including
      prothrombin, V, VII, VIII, IX, and X may be present. The plasma level of
      antithrombin is typically normal, but protein C and protein S are modestly
      reduced. Within the fibrinolytic system, slightly increased levels of tissue
      plasminogen activator accompanied by slightly increased plasminogen activator
      inhibitor-1 and decreased thrombin activatable fibrinolysis inhibitor have been
      demonstrated. These derangements are prominent in patients with DHF grades III
      and IV, collectively known as dengue shock syndrome. Moreover, patients with
      excessive depletion of intravascular volume from plasma leakage and/or massive
      bleeding from endothelial dysfunction, thrombocytopenia, platelet dysfunction,
      and coagulopathy may exhibit shock, prolonged shock and repeated shock. DIC is
      also commonly found in these complicated patients. However, most patients recover
      spontaneously with normalization of abnormal laboratory profiles during the
      convalescent stage or within one to two weeks after defervescence. 

PMID- 24120238
TI  - The role of intraplatelet reactive oxygen species in the regulation of platelet
      glycoprotein Ibalpha ectodomain shedding.
AB  - Glycoprotein (GP) Ibalpha ectodomain shedding has become a generally accepted
      negative regulatory mechanism of platelet function. Stimulation of platelet with
      either physiological or chemical compound results in GPIbalpha ectodomain
      shedding in vitro and in vivo, the mechanism, however, is not totally understood.
      Here we show, collagen, thrombin, and calcium ionophore A23187 induce reactive
      oxygen species (ROS) generation, and simultaneously incur GPIbalpha ectodomain
      shedding. ROS scavengers N-acetylcysteine (NAC) and dithiothreitol (DTT) abolish
      not only collagen, thrombin, and A23187 induced ROS production, but also
      GPIbalpha ectodomain shedding. Interestingly, a recognized calpain activator,
      dibucaine, induces both ROS production and GPIbalpha shedding, which are also
      obviously reduced by NAC and DTT. Furthermore, calpain inhibitors calpain
      inhibitor I and carbobenzoxy-valinyl-phenylalaninal, obviously reduce dibucaine,
      thrombin, and A23187-induced ROS generation. These data indicate that ROS plays a
      key role in collagen, thrombin, and A23187-induced GPIbalpha ectodomain shedding.
      Calpain is an up-stream regulator that regulates ROS-mediated GPIbalpha shedding.

PMID- 24120239
TI  - Chemokine receptor CXCR4: role in gastrointestinal cancer.
AB  - Chemokines (CK)s, small proinflammatory chemoattractant cytokines that bind to
      specific G-protein coupled seven-span transmembrane receptors, are major
      regulators of cell trafficking and adhesion. The CXCL12 [stromal cell-derived
      factor-1 (SDF-1)] binds primarily to CXC receptor 4 (CXCR4; CD184). The binding
      of CXCL12 to CXCR4 induces intracellular signaling through several divergent
      pathways initiating signals related to chemotaxis, cell survival and/or
      proliferation, increase in intracellular calcium, and gene transcription. CXCR4
      is expressed on multiple cell types including lymphocytes, hematopoietic stem
      cells, endothelial and epithelial cells, and cancer cells. One of the most
      intriguing and perhaps important roles that CKs and the CK receptors have is in
      regulating metastasis. Here, CK receptors may potentially facilitate tumor
      dissemination at each of the key steps of metastasis, including adherence of
      tumor cells to endothelium, extravasation from blood vessels, metastatic
      colonization, angiogenesis, proliferation, and protection from the host response
      via activation of key survival pathways such as ERK/MAPK, PI-3K/Akt/mTOR, or
      Jak/STAT, etc. In addition, it is increasingly recognized that CKs play an
      important role in facilitating communication between cancer cells and non
      neoplatic cells in the tumor microenvironment (TME), including endothelial cells
      and fibroblasts, promoting the infiltration, activation of neutrophils, and tumor
      associated macrophages within the TME. In this review, we mainly focus on the
      roles of chemokines CXCL12 and its cognate receptors CXCR4 as they pertain to
      cancer progression. In particular, we summarizes our current understanding
      regarding the contribution of CXCR4 and SDF-1 to gastrointestinal tumor behavior
      and its role in local progression, dissemination, and immune evasion of tumor
      cells. Also, describes recent therapeutic approaches that target these receptors
      or their ligands.

PMID- 24120240
TI  - Inhibition of lung inflammatory responses by bornyl acetate is correlated with
      regulation of myeloperoxidase activity.
AB  - BACKGROUND: Bornyl acetate is a bicyclic monoterpene present in numerous conifer
      oils. In this study, we aimed at clarifying the potential anti-inflammatory
      function and mechanism of bornyl acetate by using lipopolysaccharide (LPS)
      induced acute lung injury murine model and RAW 264.7 cells. MATERIALS AND
      METHODS: RAW 264.7 cells were pretreated with bornyl acetate 1 h before LPS
      stimulation and cell-free super supernatants were collected to measure cytokine
      concentrations. To induce acute lung injury, BALB/c mice were injected
      intranasally with LPS and treated with bornyl acetate 1 h before LPS stimulation.
      Seven hours after administration, the bronchoalveolar lavage fluid (BALF) was
      collected for measuring the cell count and cytokine production. We collected
      lungs for assaying wet-to-dry weight ratio, myeloperoxidase activity, and
      histologic changes. The extent of phosphorylation of mitogen-activated protein
      kinases and nuclear factor kappaB was detected by Western blot. RESULTS: Our
      results showed that bornyl acetate downregulated the levels of proinflammatory
      cytokines in vitro and in vivo; reduced the number of total cells, neutrophils,
      and macrophages in BALF; attenuated the histologic alterations in the lung;
      decreased the wet-to-dry weight ratio in BALF; and suppressed NF-kappa-B
      inhibitor alpha, extracellular regulated protein kinases, c-JunN-terminal kinase,
      p38 mitogen-activated protein kinase activation. CONCLUSIONS: These findings
      suggested that bornyl acetate may be developed as a preventive agent for lung
      inflammatory diseases.

PMID- 24120241
TI  - Role of tumor-infiltrating CD11b+ antigen-presenting cells in the progression of
      gastric cancer.
AB  - BACKGROUND: Tumor-infiltrating antigen-presenting cells (APCs), involving tumor
      associated macrophages and tumor-infiltrating dendritic cells, play an important
      role in tumor immunity and immune escape. The aim of this study was to determine
      whether tumor infiltrating CD11b(+) APCs may affect tumor progression and
      clinical outcome. METHODS: The immunohistochemical analysis was used to evaluate
      the expression of CD11b, FOXP3, and CD8 in 214 gastric cancer tissues.
      Concentrations of immunosuppressive cytokines in medium conditioned by gastric
      cancer cells were measured by enzyme-linked immunosorbent assay. Effects of
      addition of tumor-conditioned media on CD11c(+) cells were examined by flow
      cytometry. RESULTS: Almost all tumor-infiltrating CD11b(+) cell expressed CD11c
      and was considered to be APCs. High CD11b(+) cell infiltration was significantly
      correlated with huge tumor, positive venous invasion, lymph node metastasis, and
      tumor, node, metastasis stage. Patients with high CD11b(+) cell infiltration had
      a poorer surgical outcome than those with low CD11b infiltration. Multivariate
      analysis revealed that CD11b(+) cell infiltration was one of the independent
      prognostic factors. Tumor-conditioned medium obtained from several gastric cancer
      cell lines contained immunosuppressive cytokines, transforming growth factor
      beta, interleukin-10, and vascular endothelial growth factor. The addition of
      tumor-conditioned medium decreased the expression of major histocompatibility
      complex-II and increased the expression of CD11b and programmed death ligand 2 on
      CD11c(+) APCs. Infiltration of CD11b(+) cells significantly correlate with the
      degree of FOXP3(+) cell infiltration but not with CD8(+) cell infiltration.
      CONCLUSIONS: Tumor-infiltrating CD11b(+) APCs affected local tumor cell-immune
      cell interactions and correlated to the poor prognosis of the patients with
      gastric cancer.

PMID- 24120242
TI  - Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in
      rats: the roles of phosphatidylinositol 3-kinase and nitric oxide.
AB  - BACKGROUND: Ischemic postconditioning (PostC) protects the liver against ischemia
      reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been
      reported to exhibit preconditioning properties against hepatic IR injury;
      however, its PostC properties remain unknown. This study investigated whether
      milrinone has PostC properties against hepatic IR injury and the roles of
      phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS). MATERIALS
      AND METHODS: Male Wistar rats were separated into six groups: (1) group S:
      animals that underwent sham operation without ischemia, (2) group C: ischemia
      followed by reperfusion with no other intervention, (3) group M: milrinone
      administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K
      inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS
      inhibitor, injected before milrinone administration, and (6) group MD, milrinone
      administered 30 min after reperfusion. Except for group S, all groups underwent 1
      h of warm ischemia of median and left lateral lobes, followed by 5 h of
      reperfusion. Biochemical liver function analysis and histologic examination were
      performed. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase,
      and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in
      group M were significantly lower than those in group C. The inhibition of PI3K or
      NOS prevented this protective effect. Milrinone administered 30 min after
      reperfusion did not show obvious protective effects. CONCLUSIONS: Milrinone
      induced PostC protects against hepatic IR injury when it is administered
      immediately after reperfusion, and PI3K and NOS may play an important role in
      this protective effect.

PMID- 24120243
TI  - Should abstracts for rehabilitation congresses be subject to more rigorous
      selection?

PMID- 24120244
TI  - Rehabilitation of 190 non-ambulatory children with cerebral palsy in structures
      of care or in liberal sector.
AB  - AIMS: To describe the rehabilitation of non-ambulatory children with cerebral
      palsy and to explore adjustability on their individual needs. MATERIAL AND
      METHOD: Data described are extracted from an on-going national cohort study,
      following during 10years 385 children with cerebral palsy, aged from 4 to 10,
      Gross Motor Function Classification System IV and V. We analysed data from the
      first 190 patients (mean age 6years 10months (SD 2.0), 111 boys), focusing on
      physiotherapy, ergotherapy, psychomotility and speech therapy in medico-social
      and liberal sectors. RESULTS: In medico-social sector, duration of paramedical
      care is significantly more important than in liberal sector (structure of care:
      median=4.25h/week, liberal sector: median=2.00h/week) (P<0.0001). More than 4
      different types of care per week are given in medico-social sector, while in
      liberal sector children benefit from only 2 different types of care a week. In
      investigators opinion, rehabilitation in structures of care is 71.65% adapted as
      opposed to 18.75% in the liberal sector (P<0.001). Children level V have less
      time of rehabilitation than the others (P=0.0424). INTERPRETATION: Rehabilitation
      of children with cerebral palsy who are not able to walk, with an objective to
      improve quality of life, is truly multidisciplinary and suitable in medico-social
      sector.

PMID- 24120245
TI  - Hemifacial spasm revealing contralateral peripheral facial palsy.

PMID- 24120247
TI  - Response to Dr. Szarewski.

PMID- 24120246
TI  - Quantification of neonatal amplitude-integrated EEG patterns.
AB  - BACKGROUND: Amplitude-integrated EEG (aEEG) is increasingly used in research with
      premature infants; however, comprehensive interpretation is limited by the lack
      of simple approaches for reliably quantifying and summarizing the data. AIM:
      Explore operational measures for quantifying continuity and discontinuity,
      measured by aEEG as components of infant brain function. STUDY DESIGN: An
      exploratory naturalistic study of neonates while in the Neonatal Intensive Care
      Unit (NICU). One single channel aEEG recording per infant was obtained without
      disruption of nursing care practices. SUBJECTS: 24 infants with mean
      postmenstrual age (PMA) of 33.11 weeks (SD 3.49), average age of 2.62 weeks (SD
      1.35) and mean birth weights of 1.39 kg (SD 0.73). OUTCOME MEASURES:
      Quantification of continuity and discontinuity included bandwidth and lower
      border of aEEG, calculated proportion of time with signal amplitude below 10 MUV,
      and peak counts. Variance of bandwidth and lower border denoted cycling. RESULTS:
      Group mean bandwidth was 52.98 MUV (SD 27.62). Median peak count in 60 second
      epochs averaged 3.63 (SD 1.74), while median proportion < 10 MUV was 22% (SD
      0.20). The group mean of lower border within-subject aggregated medians was 6.20
      MUV (SD 2.13). Group mean lower border standard deviation was 3.96 MUV.
      Proportion < 10 MUV showed a strong negative correlation with the natural log of
      the lower border median (r = -0.906, p < .0001) after controlling for PMA.
      CONCLUSIONS: This study introduces a novel quantification process by counting
      peaks and proportion of time < 10 MUV. Expanded definitions and analytic
      techniques will serve to strengthen the application of existing scoring systems
      for use in naturalistic research settings and clinical practice.

PMID- 24120248
TI  - The COX-2 inhibitor meloxicam prevents pregnancy when administered as an
      emergency contraceptive to nonhuman primates.
AB  - OBJECTIVE: Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and
      disrupt essential reproductive processes. Ultrasound studies in women
      demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse
      associated with ovulation. The goal of this study was to determine if oral
      administration of a COX-2 inhibitor can inhibit reproductive function with
      sufficient efficacy to prevent pregnancy in primates. STUDY DESIGN: The COX-2
      inhibitor meloxicam (or vehicle) was administered orally to proven fertile female
      cynomolgus macaques using one emergency contraceptive model and three monthly
      contraceptive models. In the emergency contraceptive model, females were bred
      with a proven fertile male once 2+/-1 days before ovulation, returned to the
      females' home cage, and then received 5 days of meloxicam treatment. In the
      monthly contraceptive models, females were co-caged for breeding with a proven
      fertile male for a total of 5 days beginning 2+/-1 days before ovulation. Animals
      received meloxicam treatment (1) cycle days 5-22, or (2) every day, or (3) each
      day of the 5-day breeding period. Female were then assessed for pregnancy.
      RESULTS: The pregnancy rate with meloxicam administration using the emergency
      contraception model was 6.5%, significantly lower than the pregnancy rate of
      33.3% when vehicle without meloxicam was administered. Pregnancy rates with the
      three monthly contraceptive models (75%-100%) were not consistent with preventing
      pregnancy. CONCLUSIONS: Oral COX-2 inhibitor administration can prevent pregnancy
      after a single instance of breeding in primates. While meloxicam may be
      ineffective for regular contraception, pharmacological inhibition of COX-2 may be
      an effective method of emergency contraception for women. IMPLICATIONS: COX-2
      inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs
      of this class has not been directly tested. This study, conducted in nonhuman
      primates, is the first to suggest that a COX-2 inhibitor may be effective as an
      emergency contraceptive.

PMID- 24120249
TI  - Translating access into utilization: lessons from the design and evaluation of a
      health insurance Web site to promote reproductive health care for young women in
      Massachusetts.
AB  - BACKGROUND: Following state-level health care reform in Massachusetts, young
      women reported confusion over coverage of contraception and other sexual and
      reproductive health services under newly available health insurance products. To
      address this gap, a plain-language Web site titled "My Little Black Book for
      Sexual Health" was developed by a statewide network of reproductive health
      stakeholders. The purpose of this evaluation was to assess the health literacy
      demands and usability of the site among its target audience, women ages 18-26
      years. STUDY DESIGN: We performed an evaluation of the literacy demands of the
      Web site's written content and tested the Web site's usability in a health
      communications laboratory. RESULTS: Participants found the Web site visually
      appealing and its overall design concept accessible. However, the Web site's
      literacy demands were high, and all participants encountered problems navigating
      through the Web site. Following this evaluation, the Web site was modified to be
      more usable and more comprehensible to women of all health literacy levels.
      CONCLUSIONS: To avail themselves of sexual and reproductive health services newly
      available under expanded health insurance coverage, young women require
      customized educational resources that are rigorously evaluated to ensure
      accessibility. IMPLICATIONS: To maximize utilization of reproductive health
      services under expanded health insurance coverage, US women require customized
      educational resources commensurate with their literacy skills. The application of
      established research methods from the field of health communications will enable
      advocates to evaluate and adapt these resources to best serve their targeted
      audiences.

PMID- 24120250
TI  - Impact of tubal ligation on ovarian reserve as measured by anti-Mullerian hormone
      levels: a prospective cohort study.
AB  - BACKGROUND: Tubal ligation (TL) is considered a very efficient contraceptive
      method. However, some patients complain of a variety of postoperative symptoms.
      The objective of this study was to investigate whether ovarian reserve may change
      after tubal ligation. STUDY DESIGN: This was a prospective cohort study of 80
      fertile women who underwent TL. Ovarian reserve was evaluated by measuring pre-
      and postoperative (1 year after surgery) serum anti-Mullerian hormone (AMH)
      levels and transvaginal antral follicular count (AFC). Potential confounding
      factors were age, body mass index (BMI), smoking, surgical technique and prior
      contraceptive methods. The Wilcoxon test was used to compare pre- and
      postoperative (12 months) AMH and AFC, and simple and multiple linear regression
      were used to evaluate confounding factors. RESULTS: Fifty-two patients completed
      the study protocol. The median AMH level was 1.43 ng/mL (interquartile range 0.63
      2.62) preoperatively and 1.30 ng/mL (interquartile range 0.53-2.85) after 12
      months (p=.23). The mean AFC was 8.0 (interquartile range 5.0-14.0) and 11.0
      (interquartile range 7.0-15.0) before and after TL, respectively (p=.12). These
      differences were not statistically significant. Use of a hormonal contraceptive
      method prior to TL was significantly associated with a postoperative increase in
      AMH. CONCLUSIONS: This study suggests that ovarian reserve is not altered by TL.

PMID- 24120251
TI  - "Is it worth risking your life?" Ethnography, risk and death on the U.S.-Mexico
      border.
AB  - Every year, several hundred people die attempting to cross the border from Mexico
      into the United States, most often from dehydration and heat stroke though snake
      bites and violent assaults are also common. This article utilizes participant
      observation fieldwork in the borderlands of the US and Mexico to explore the
      experience of structural vulnerability and bodily health risk along the desert
      trek into the US. Between 2003 and 2005, the ethnographer recorded interviews and
      conversations with undocumented immigrants crossing the border, border patrol
      agents, border activists, borderland residents, and armed civilian vigilantes. In
      addition, he took part in a border crossing beginning in the Mexican state of
      Oaxaca and ending in a border patrol jail in Arizona after he and his
      undocumented Mexican research subjects were apprehended trekking through the
      borderlands. Field notes and interview transcriptions provide thick ethnographic
      detail demonstrating the ways in which social, ethnic, and citizenship
      differences as well as border policies force certain categories of people to put
      their bodies, health, and lives at risk in order for them and their families to
      survive. Yet, metaphors of individual choice deflect responsibility from global
      economic policy and US border policy, subtly blaming migrants for the danger -
      and sometimes death - they experience. The article concludes with policy changes
      to make US-Mexico labor migration less deadly. 

PMID- 24120252
TI  - Pulmonary hypertension in obesity-hypoventilation syndrome.
AB  - BACKGROUND: Pulmonary hypertension (PH) is considered a clinically important
      feature of Obesity-Hypoventilation Syndrome (OHS). We aimed to determine
      prevalence, characteristics and severity of PH including associations with
      clinical outcomes after established non-invasive positive pressure ventilation
      (NPPV). METHODS: In a prospective cross-sectional study, clinically stable OHS
      patients (NPPV duration >= 3 months) were consecutively assessed using
      echocardiography, serum markers and right-heart catheterization (RHC). NPPV use
      was quantified via ventilator counters. Blood gases, lung function, Epworth
      Sleepiness Scale (ESS), sleep-quality, WHO-functional class (WHO-FC), 6-min walk
      distance, and health-related quality of life (HRQL) via Severe Respiratory
      Insufficiency (SRI) questionnaire were assessed. RESULTS: Of 177 patients
      considered, 64 fulfilled inclusion criteria. Among these, 21 patients (10
      female/11 male; BMI 45 [40; 53] kg/m(2), PaCO2 39.6 [37.8; 45.5] mmHg (median
      [quartiles])) gave consent for RHC. Four patients (19%) had normal mean pulmonary
      artery pressure (mPAP < 20 mmHg), 8 (38.1%) mPAP 20-24 mmHg and 9 (42.9%)
      manifest PH (mPAP >= 25 mmHg), 3 of them with combined pre- and/or postcapillary
      PH. mPAP was negatively correlated to NPPV use, vital capacity and lung diffusing
      capacity (p < 0.01 each), and positively to BMI (p < 0.05). NPPV use and vital
      capacity independently predicted mPAP. In patients with PH, ESS, WHO-FC, and some
      SRI-items were worse (p < 0.05 each) compared to patients without PH.
      Multivariate analyses revealed mPAP as the only independent predictor of the SRI
      physical functioning domain. CONCLUSIONS: Mild to moderate PH is frequent in
      patients with OHS despite NPPV, mPAP being inversely related to NPPV adherence.
      PH is associated with impairments in daytime-sleepiness, WHO-FC, HRQL and
      physical functioning.

PMID- 24120253
TI  - Pooled subpopulation analyses of the effects of roflumilast on exacerbations and
      lung function in COPD.
AB  - BACKGROUND: This post-hoc analysis examined the impact of roflumilast on chronic
      obstructive pulmonary disease (COPD) exacerbations and lung function in patients
      with COPD who received concomitant long-acting beta2-agonists (LABA) with or
      without prior inhaled corticosteroid (ICS) and the influence of various
      demographic and clinical characteristics on these outcomes. METHODS: Data were
      pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily
      roflumilast 500 MUg in patients with COPD. Endpoints were mean rate of
      exacerbations and change from baseline in pre- and postbronchodilator FEV1.
      RESULTS: In this pooled analysis (N = 3091), addition of roflumilast to LABAs for
      1 year in patients who discontinued ICS prior to study entry (n = 945)
      significantly reduced the risk of COPD exacerbations vs. placebo by 19.2% (p <
      0.05) and significantly improved pre- and postbronchodilator FEV1 by 40 mL and 34
      mL, respectively (both, p < 0.01). Similar improvements were observed in patients
      who received concomitant LABAs but were not taking ICS prior to study entry (n =
      597). A significant reduction in COPD exacerbation risk with roflumilast vs.
      placebo was observed regardless of age or smoking status, and in patients who had
      severe or very severe COPD. Significantly improved lung function was observed
      with roflumilast in all the subgroups (p < 0.05), with the exception of patients
      with moderate COPD. CONCLUSIONS: Roflumilast reduced exacerbation rates and
      improved lung function in patients with COPD who received concomitant LABA,
      regardless of prior ICS use, and across various patient subgroups regardless of
      age and smoking status. CLINICALTRIALSGOV REGISTRATION NUMBERS: NCT00297102 (M2
      124) and NCT00297115 (M2-125).

PMID- 24120254
TI  - Porous media properties of reticulated shape memory polymer foams and mock
      embolic coils for aneurysm treatment.
AB  - BACKGROUND: Shape memory polymer (SMP) foams are being investigated as an
      alternative aneurysm treatment method to embolic coils. The goal of both
      techniques is the reduction of blood flow into the aneurysm and the subsequent
      formation of a stable thrombus, which prevents future aneurysm rupture. The
      purpose of this study is to experimentally determine the parameters, permeability
      and form factor, which are related to the flow resistance imposed by both media
      when subjected to a pressure gradient. METHODS: The porous media properties
      permeability and form factor-of SMP foams and mock embolic coils (MECs) were
      measured with a pressure gradient method by means of an in vitro closed flow
      loop. We implemented the Forchheimer-Hazen-Dupuit-Darcy equation to calculate
      these properties. Mechanically-reticulated SMP foams were fabricated with average
      cell sizes of 0.7E-3 and 1.1E-3 m, while the MECs were arranged with volumetric
      packing densities of 11-28%. RESULTS: The permeability of the SMP foams was an
      order of magnitude lower than that of the MECs. The form factor differed by up to
      two orders of magnitude and was higher for the SMP foams in all cases. The
      maximum flow rate of all samples tested was within the inertial laminar flow
      regime, with Reynolds numbers ranging between 1 and 35. CONCLUSIONS: The SMP
      foams impose a greater resistance to fluid flow compared to MECs, which is a
      result of increased viscous and inertial losses. These results suggest that
      aneurysms treated with SMP foam will have flow conditions more favorable for
      blood stasis than those treated with embolic coils having packing densities <=
      28%.

PMID- 24120255
TI  - [Pancreatic adenocarcinoma during pregnancy].

PMID- 24120256
TI  - Hypernephroma with tumor thrombus of the inferior vena cava.

PMID- 24120257
TI  - [Treatment of hemorraghic pancreatic pseudocyst by selective embolization of the
      splenic artery].

PMID- 24120258
TI  - Do programs designed to train working memory, other executive functions, and
      attention benefit children with ADHD? A meta-analytic review of cognitive,
      academic, and behavioral outcomes.
AB  - Children with ADHD are characterized frequently as possessing underdeveloped
      executive functions and sustained attentional abilities, and recent commercial
      claims suggest that computer-based cognitive training can remediate these
      impairments and provide significant and lasting improvement in their attention,
      impulse control, social functioning, academic performance, and complex reasoning
      skills. The present review critically evaluates these claims through meta
      analysis of 25 studies of facilitative intervention training (i.e., cognitive
      training) for children with ADHD. Random effects models corrected for publication
      bias and sampling error revealed that studies training short-term memory alone
      resulted in moderate magnitude improvements in short-term memory (d=0.63),
      whereas training attention did not significantly improve attention and training
      mixed executive functions did not significantly improve the targeted executive
      functions (both nonsignificant: 95% confidence intervals include 0.0). Far
      transfer effects of cognitive training on academic functioning, blinded ratings
      of behavior (both nonsignificant), and cognitive tests (d=0.14) were
      nonsignificant or negligible. Unblinded raters (d=0.48) reported significantly
      larger benefits relative to blinded raters and objective tests (both p<.05),
      indicating the likelihood of Hawthorne effects. Critical examination of training
      targets revealed incongruence with empirical evidence regarding the specific
      executive functions that are (a) most impaired in ADHD, and (b) functionally
      related to the behavioral and academic outcomes these training programs are
      intended to ameliorate. Collectively, meta-analytic results indicate that claims
      regarding the academic, behavioral, and cognitive benefits associated with extant
      cognitive training programs are unsupported in ADHD. The methodological
      limitations of the current evidence base, however, leave open the possibility
      that cognitive training techniques designed to improve empirically documented
      executive function deficits may benefit children with ADHD. 

PMID- 24120259
TI  - Personalized tacrolimus doses determined by CYP3A5 genotype for induction and
      maintenance phases of kidney transplantation.
AB  - BACKGROUND: Cytochrome P450 (CYP) 3A4 and 3A5 are major isoforms involved in the
      metabolism of tacrolimus, with the CYP3A5 gene being more polymorphic. It is
      hypothesized that individual variation in the metabolism of tacrolimus drug may
      result from genetic polymorphism of CYP3A5. It has been reported that the
      clearance of tacrolimus in patients with the CYP3A5*1 allele was ~2.5-fold
      greater than that in those with the CYP3A5*3/*3 genotype. Recent data have also
      shown that polymorphism in exon 26 (C3435T) of the multidrug resistance gene
      (MDR1) was correlated with the expression level and function of P-glycoprotein in
      the lower duodenum, making the relationship between polymorphism of MDR1 and the
      effective dose of tacrolimus a source of controversy. OBJECTIVES: This study
      investigated the influence of genetic polymorphisms of CYP3A5 and MDR1 on the
      dose requirements for the induction and maintenance phases of tacrolimus therapy
      in kidney transplant recipients. METHODS: Sixty-eight kidney transplant
      recipients were enrolled, and their clinical and laboratory data were
      retrospectively reviewed after 6 months of tacrolimus administration. Genotypes
      of CYP3A5*1 and CYP3A5*3 and exon 26 of MDR1 (C3435T) were determined by the
      single-nucleotide polymorphism genotyping method. RESULTS: The frequencies of
      CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1 were 44.1%, 35.3%, and 20.6%,
      respectively. The mean dose of tacrolimus required for the induction phase was
      significantly greater in the CYP3A5*1/*1 group (0.142 [0.050] mg/kg/d) than that
      required in the CYP3A5*1/*3 group (0.097 [0.040] mg/kg/d; P = 0.072) and in the
      CYP3A5*3/*3 group (0.077 [0.020] mg/kg/d; P = 0.005). The maintenance dose of
      tacrolimus required in the CYP3A5*1/*1 group (0.12 [0.03] mg/kg/d) was 1.3-fold
      higher than that in the CYP3A5*1/*3 group (0.09 [0.03] mg/kg/d; P = 0.018) and
      2.4-fold higher than in the CYP3A5*3/*3 group (0.05 [0.02] mg/kg/d; P < 0.0001).
      No statistically significant relationship was observed between the doses of
      tacrolimus required for the induction and maintenance phases and MDR1
      polymorphism. CONCLUSION: Determination of the CYP3A5 genotype would be helpful
      in the design of adequate immunosuppressive treatment and in lowering toxicity by
      predicting the doses of tacrolimus required for the induction and maintenance
      phases in individual kidney transplant recipients.

PMID- 24120260
TI  - Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a
      new biomarker for smoking.
AB  - BACKGROUND: Smoking is the largest preventable cause of morbidity and mortality
      in the United States. In previous work, we demonstrated that altered DNA
      methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with
      self-reported smoking in 19-year-old African Americans with relatively low levels
      of smoking. However, one limitation of the prior work is that it was based on
      self-reported data only. Therefore, the relationship of AHRR methylation to
      smoking in older subjects and to indicators such as serum cotinine levels remains
      unknown. To address this question, we examined the relationship between genome-
      wide DNA methylation and smoking status as indicated by serum cotinine levels in
      a cohort of 22-year-old African American men. RESULTS: Consistent with prior
      findings, smoking was associated with significant DNA demethylation at two
      distinct loci within AHRR (cg05575921 and cg21161138) with the degree of
      demethylation being greater than that observed in the prior cohort of 19-year-old
      smoking subjects. Additionally, methylation status at the AHRR residue
      interrogated by cg05575921 was highly correlated with serum cotinine levels
      (adjusted R2 = 0.42, P < 0.0001). CONCLUSIONS: We conclude that AHRR DNA
      methylation status is a sensitive marker of smoking history and could serve as a
      biomarker of smoking that could supplement self-report or existing biomarker
      measures in clinical or epidemiological analyses of the effects of smoking. In
      addition, if properly configured as a clinical assay, the determination of AHRR
      methylation could also be used as a screening tool in efforts to target
      antismoking interventions to nascent smokers in the early phases of smoking.

PMID- 24120261
TI  - Integrative regulatory network of plant thylakoid energy transduction.
AB  - Highly flexible regulation of photosynthetic light reactions in plant
      chloroplasts is a prerequisite to provide sufficient energy flow to downstream
      metabolism and plant growth, to protect light reactions against photodamage, and
      to ensure controlled cellular signaling from the chloroplast to the nucleus. Such
      comprehensive regulation occurs via the control of excitation energy transfer to
      and between the two photosystems (PSII and PSI), of the electrochemical gradient
      across the thylakoid membrane (DeltapH), and of electron transfer from PSII to
      PSI electron acceptors. In this opinion article, we propose that these regulatory
      mechanisms, functioning at different levels of photosynthetic energy conversion,
      might be interconnected and describe how the concomitant and integrated function
      of these mechanisms might enable plants to acclimate to a full array of
      environmental changes. 

PMID- 24120262
TI  - Factors that led to the implementation of the efficiency frontier approach in
      health economic evaluation in Germany: do not avoid the elephant in the room.
      Comment on Klingler et al. (Health Policy 109 (2013) 270-280).

PMID- 24120263
TI  - Accentuate or repeat? Brain signatures of developmental periods in infant word
      recognition.
AB  - Language acquisition has long been discussed as an interaction between biological
      preconditions and environmental input. This general interaction seems
      particularly salient in lexical acquisition, where infants are already able to
      detect unknown words in sentences at 7 months of age, guided by phonological and
      statistical information in the speech input. While this information results from
      the linguistic structure of a given language, infants also exploit situational
      information, such as speakers' additional word accentuation and word repetition.
      The current study investigated the developmental trajectory of infants'
      sensitivity to these two situational input cues in word recognition. Testing
      infants at 6, 9, and 12 months of age, we hypothesized that different age groups
      are differentially sensitive to accentuation and repetition. In a familiarization
      test paradigm, event-related brain potentials (ERPs) revealed age-related
      differences in infants' word recognition as a function of situational input cues:
      at 6 months infants only recognized previously accentuated words, at 9 months
      both accentuation and repetition played a role, while at 12 months only
      repetition was effective. These developmental changes are suggested to result
      from infants' advancing linguistic experience and parallel auditory cortex
      maturation. Our data indicate very narrow and specific input-sensitive periods in
      infant word recognition, with accentuation being effective prior to repetition. 

PMID- 24120264
TI  - Changes in predicted cardiovascular disease risk after biliopancreatic diversion
      surgery in severely obese patients.
AB  - OBJECTIVE: To determine the impact of biliopancreatic diversion with duodenal
      switch (BPD-DS) surgery on cardiovascular risk profile and predicted
      cardiovascular risk in severely obese patients. MATERIALS/METHODS: We compared 1
      year follow-up anthropometric and metabolic profiles in severely obese who
      underwent BPD-DS (n = 73) with controls (severely obese without surgery) (n =3
      3). The 10-year predicted risk for coronary heart disease (CHD) was estimated
      using the Framingham risk-tool. We assigned 10-year and lifetime predicted risks
      to stratify subjects into 3 groups: 1) high short-term predicted risk (>= 10% 10
      year risk or diagnosed diabetes), 2) low short-term (<10% 10-year risk)/low
      lifetime predicted risk or 3) low short-term/high lifetime predicted risk.
      RESULTS: During the follow-up period, body weight and body mass index decreased
      markedly in the surgical group (-52.1 +/- 1.9 kg and -19.0 +/- 0.6 kg/m(2)
      respectively, p<0.001) vs. (-0.7 +/- 1.0 kg and -0.3 +/- 0.4 kg/m(2), p = 0.51).
      Weight loss in the surgical group was associated with a reduction in HbA1C (6.2%
      vs. 5.1%), HOMA-IR (61.5 vs. 9.3), all lipoprotein levels, as well as blood
      pressure (p<0.001). The 10-year CHD predicted risk decreased by 43% in women and
      33% in men, whereas the estimated CHD risk in the non surgical group did not
      change. Before surgery, none of the women and only 18% of men showed low short
      term/low lifetime predicted risk, whereas a significant proportion of subjects
      had high short-term predicted risk (36% in women and 12% in men). Following
      surgery, 52% of women and 55% of men have a low short-term/low lifetime predicted
      risk. CONCLUSIONS: These results highlight the cardiovascular benefits of BPD-DS
      and suggest a positive impact on predicted CHD risk in severely obese patients.
      Long-term studies are needed to confirm our results and to ascertain the effects
      on CHD risk estimates after BPD-DS surgery.

PMID- 24120265
TI  - Atypical yeasts identified as Saccharomyces cerevisiae by MALDI-TOF MS and gene
      sequencing are the main responsible of fermentation of chicha, a traditional
      beverage from Peru.
AB  - Chicha is a drink prepared in several Andean countries from Inca's times by maize
      fermentation. Currently this fermentation is carried out in familiar artesanal
      "chicherias" that make one of the most known types of chicha, the "chicha de
      jora". In this study we isolate and identify the yeasts mainly responsible of the
      fermentation process in this type of chicha in 10 traditional "chicherias" in
      Cusco region in Peru. We applied by first time MALDI-TOF MS analysis for the
      identification of yeast of non-clinic origin and the results showed that all of
      yeast strains isolated belong to the species Saccharomyces cerevisiae. These
      results agree with those obtained after the analysis of the D1/D2 and 5.8S-ITS
      regions. However the chicha strains have a phenotypic profile that differed in
      more than 40% as compared to that of current S. cerevisiae strains. To the best
      of our knowledge this is the first report concerning the yeasts involved in
      chicha fermentation. 

PMID- 24120266
TI  - Workplace aggression prevention and minimisation in Australian clinical medical
      practice settings - a national study.
AB  - INTRODUCTION: This report describes the extent to which 12 workplace aggression
      prevention and minimisation actions have been implemented in Australian clinical
      medical practice settings. METHODS: Using a cross-sectional, self-report survey
      conducted as part of a national longitudinal study of the Australian medical
      workforce, differences in the proportions of medical clinicians reporting the
      implementation of 12 aggression prevention and minimisation actions in their main
      workplace were determined. RESULTS: Only one-third of aggression prevention and
      minimisation actions achieved point-prevalence rates of greater than 60%,
      including aggression policies and protocols (65.7%) and incident reporting
      systems (68.2%). Overall, lower point-prevalence rates were detected for general
      practitioners and specialists compared with hospital non-specialists and
      specialists in training, largely reflecting those for doctors mainly working in
      private rooms compared with public hospitals. Key environmental interventions had
      relatively low point-prevalence overall, including duress alarms and optimised
      clinician escape in consulting and treatment areas, and after-hours and off-site
      safety strategies. CONCLUSIONS: More widespread adoption of aggression prevention
      and minimisation measures in medical practice settings is required. Specific
      legislative and accreditation provisions and funding support may provide the
      necessary impetus for reform. Further studies can enhance the evidence base on
      the most effective approaches to the prevention and minimisation of workplace
      aggression in medical practice settings.

PMID- 24120267
TI  - Unusual transformation of substituted-3-formylchromones to pyrimidine analogues:
      synthesis and antimicrobial activities of 5-(o-hydroxyaroyl)pyrimidines.
AB  - Substituted-3-formylchromones (4a-e) on reaction with 1,3-bis
      dimethylaminomethylene-thiourea (5) in refluxing toluene solution give novel
      substituted 5-(o-hydroxyaroyl)pyrimidines (6a-e) in high yields. A mechanistic
      rationalization of the formation of products (6a-e) is proffered. Antimicrobial
      activities of all the synthesized compounds (6a-e) were evaluated against various
      fungal and bacterial strains. Compound 6d display significant antifungal activity
      (MIC 15) against Geotrichum candidum in comparison fluconazole used as positive
      control. Some of the compounds also display good antibacterial activity.
      Cytotoxic profile of compound 6d against HeLa cells indicates that at
      concentration (20 MUM) no significant cell death (~2%) was observed.

PMID- 24120268
TI  - [Coverage of a hand palmar defect by a synovial flap of the flexor digitorum
      superficialis].
AB  - Post-traumatic palmar soft tissue defects are a difficult problem in plastic
      surgery and many techniques have been described. We report the case of a 41-year
      old patient with a large palmar soft tissue defect of the right hand due to a
      work accident. The classical flaps used in this indication were not usable. So,
      we chose the synovial flap of the Flexor digitorum superficialis to cover this
      palmar defect. We discuss the coverage possibilities for a hand palmar defect in
      emergency, and the use of the synovial flap in this indication. This case report
      shows that the synovial flap could be an option for the coverage of palmar soft
      tissue defects. 

PMID- 24120269
TI  - Oxytocin's impact on social face processing is stronger in homosexual than
      heterosexual men.
AB  - Oxytocin is an evolutionarily highly preserved neuropeptide that contributes to
      the regulation of social interactions including the processing of facial stimuli.
      We hypothesized that its improving effect on social approach behavior depends on
      perceived sexual features and, consequently, on sexual orientation. In 19
      homosexual and 18 heterosexual healthy young men, we investigated the acute
      effect of intranasal oxytocin (24IU) and placebo, respectively, on the processing
      of social stimuli as assessed by ratings of trustworthiness, attractiveness and
      approachability for male and female faces. Faces were each presented with a
      neutral, a happy, and an angry expression, respectively. In heterosexual
      subjects, the effect of oxytocin administration was restricted to a decrease in
      ratings of trustworthiness for angry female faces (p<0.02). In contrast, in
      homosexual men oxytocin administration robustly increased ratings of
      attractiveness and approachability for male faces regardless of the facial
      expression (all p <= 0.05), as well as ratings of approachability for happy
      female faces (p<0.01). Results indicate that homosexual in comparison to
      heterosexual men display higher sensitivity to oxytocin's enhancing impact on
      social approach tendencies, suggesting that differences in sexual orientation
      imply differential oxytocinergic signaling.

PMID- 24120270
TI  - Ultrasonic flaw detection using threshold modified S-transform.
AB  - Interference noising originating from the ultrasonic testing defect signal
      seriously influences the accuracy of the signal extraction and defect location.
      Time-frequency analysis methods are mainly used to improve the defects detection
      resolution. In fact, the S-transform, a hybrid of the Short time Fourier
      transform (STFT) and wavelet transform (WT), has a time frequency resolution
      which is far from ideal. In this paper, a new modified S-transform based on
      thresholding technique, which offers a better time frequency resolution compared
      to the original S-transform is proposed. The improvement is achieved by the
      introduction of a new scaling rule for the Gaussian window used in S-transform.
      Simulation results are presented and show correct time frequency information of
      multiple Gaussian echoes under low signal-to-noise ratio (SNR) environment. In
      addition, experimental results demonstrate better and reliable detection of close
      echoes drowned in the noise. 

PMID- 24120271
TI  - Development of a short form of Stroke-Specific Quality of Life Scale for patients
      after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: The identification of aneurysmal subarachnoid hemorrhage (aSAH)
      patients with a decrease in health-related quality of life (HRQOL) is
      challenging. Stroke-Specific Quality of Life (SS-QOL) Scale is one of the
      commonest disease-specific quality of life measures initially developed and
      validated for ischemic stroke patients. A disadvantage is subject burden and a
      short form is more practical to use in clinical and research setting. AIM: This
      study aimed to develop a short form (12-item) of a Chinese version of Stroke
      Specific Quality of Life Scale for aSAH (SSQOL-a) for clinical and research
      applications. METHODS: We carried out a prospective observational assessor
      blinded multi-center study in Hong Kong. The study was registered at
      ClinicalTrials.gov of the U.S. National Institutes of Health (NCT01038193), and
      was approved by hospital ethics committees. RESULTS: One hundred and eighty-six
      aSAH patients were recruited over a 30 month period during admission. One hundred
      (54%) aSAH patients completed the 12-month assessment battery and were included
      into the current study. The total score, physical component score, and
      psychosocial score of the 12-item Chinese version showed satisfactory internal
      consistency and explained high percentages of variance of the full Chinese
      version (92% to 96%). The 12-item Chinese version showed significant correlations
      with neurological, functional, generic quality of life, psychiatric, and
      cognitive outcome measures at 12 months. Chinese version calculated physical
      subscore had better discrimination in detecting complete recovery than the Dutch
      version calculated physical subscore in our Chinese population. CONCLUSIONS: The
      12-item Chinese version of SSQOL-a has a satisfactory internal consistency and
      criterion validity for SAH patients at 12 month assessments.

PMID- 24120272
TI  - Effects of the altered activity of delta-opioid receptor on the expression of
      glutamate transporter type 3 induced by chronic exposure to morphine.
AB  - Altered delta-opioid receptor (DOR) activity can affect the activity and function
      of excitatory amino acid transporter 3 (EAAT3), but the effects of DOR on EAAT3
      expression in morphine relapse remain unknown. In this study, a C6delta cell line
      and SD rats in a conditioned place preference (CPP) reinstatement model were
      used. Here, we show that EAAT3 protein levels in C6delta cells decreased
      significantly after chronic exposure to morphine (10 MUM) for 48 h and returned
      to normal 12 h after drug withdrawal. When C6delta cells were re-exposed to 5 MUM
      morphine for 4 h, EAAT3 protein levels again decreased significantly. The
      selective MU opioid receptor (MOR) specific agonist DAMGO had a similar effect as
      morphine, and CTOP, a specific MOR blocker, reversed the declined expression of
      EAAT3 protein triggered by morphine exposure. The selective DOR agonist [d-pen2,
      5] enkephalin (DPDPE) significantly increased EAAT3 expression in C6delta cells
      and even reversed the decreased EAAT3 expression caused by chronic morphine
      exposure. The non specific antagonist naloxone, but not the DOR inhibitor
      Naltrindole (NTI), reversed the decreased EAAT3 expression in C6delta cells
      caused by chronic morphine exposure. In vivo, EAAT3 levels in the prefrontal
      cortex of rats with morphine-induced CPP reinstatement significantly decreased.
      Naloxone completely suppressed reinstatement and reversed the decrease in EAAT3
      expression induced by morphine re-exposure. In contrast, NTI only weakened CPP
      reinstatement and exerted no influence on EAAT3 expression. These findings
      suggest that DOR can affect the expression of EAAT3. However, the morphine
      induced down-regulation of EAAT3 in C6delta cells and in the prefrontal cortex of
      rats may not be mediated by DOR.

PMID- 24120273
TI  - Cerebral involvement in spinal and bulbar muscular atrophy (Kennedy's disease): a
      pilot study of PET.
AB  - OBJECTIVE: To investigate possible cerebral involvement in patients with spinal
      and bulbar muscular atrophy (SBMA) by (18)F-fluorodeoxyglucose-positron emission
      tomography (FDG-PET). DESIGN: Ten patients with molecularly-confirmed SBMA and 5
      age- and gender-matched healthy controls were recruited for brain FDG-PET
      studies. The data were analyzed and compared using the statistical parametric
      mapping (SPM) method. RESULTS: Glucose hypometabolism in frontal areas of the
      cerebrum was found in patients with SBMA. However, no significant correlation
      with clinical variables, such as CAG repeat length, age at onset, or serum
      testosterone levels, was noted. CONCLUSIONS: The perturbation of cerebral glucose
      metabolism in patients with SBMA argues against SBMA being a pure lower motor and
      sensory neuron syndrome. Mutations in the androgen receptor gene might have a
      more widespread effect in the cerebrum than previously recognized.

PMID- 24120274
TI  - Rickettsia slovaca in immature Dermacentor marginatus and tissues from Apodemus
      spp. in the northern Apennines, Italy.
AB  - Immature Dermacentor marginatus ticks and tissues from small rodents were tested
      for infection with Rickettsia slovaca in the northern Apennines, Lucca Province,
      where tick-borne lymphadenopathy (TIBOLA) was previously reported in people.
      Prevalence of infestation with D. marginatus was 30.5% (n=131, 95% CI: 22.8
      39.2%) in Apodemus spp. and 26.5% (n=34, 95% CI: 12.9-44.4%) in Myodes glareolus,
      which were captured during 1980 trap nights in 2009 and 2010. Rickettsia slovaca
      was identified by polymerase chain reaction, targeting the gltA and OmpA genes,
      in ear biopsies from 8 out of 37 tested Apodemus (22%, 95% CI: 9.8-38.2%), but
      not from 9 M. glareolus. The prevalence of R. slovaca in D. marginatus feeding on
      Apodemus spp. was 53% in larvae (n=51, 95% CI: 38.5-67.1%) and 47.5% in nymphs
      (n=59, 95% CI: 34.3-60.9%). No larvae (0.0%, 95% CI: 0-36.9%), but one nymph
      removed from M. glareolus was positive (10%, 95% CI: 0.3-44.5%). Prevalence of R.
      slovaca in host-seeking D. marginatus larvae, collected in the same area, was 42%
      (n=38; 95% CI: 26.3-59.2%). Prevalence of R. slovaca was greater in larvae
      feeding on PCR-positive Apodemus than in those feeding on negative mice (78.6%
      vs. 37.1%). Furthermore, levels of infestation with D. marginatus larvae were
      greater for R. slovaca-positive mice. The infection of Apodemus spp. was probably
      the result of repeated bites by transovarially infected larvae. On the other
      hand, the finding of R. slovaca in mice tissues would be compatible with
      transmission from these hosts to feeding D. marginatus. Based on such a
      hypothesis, the most heavily infested Apodemus might play a role as amplifiers of
      the infection. 

PMID- 24120275
TI  - Molecular screening of oral precancer.
AB  - OBJECTIVES: Early detection and treatment of high risk premalignant mucosal
      changes of the oral cavity, will expectedly improve survival and reduce treatment
      related morbidity. Aims of this study were to evaluate a non-invasive screening
      approach and to assess the value of molecular markers to identify patients at
      risk for oral cancer. MATERIALS AND METHODS: Exfoliated cells and biopsies were
      obtained from oral leukoplakia lesions of 43 patients, of whom six developed oral
      cancer. All samples were investigated for loss of heterozygosity (LOH) at
      chromosomes 3p, 9p, 11q and 17p using microsatellite markers. On the biopsy
      specimen additional immunohistochemical staining for p53, TP53 mutation analysis
      and histopathological grading were performed. RESULTS: The analytical sensitivity
      of the non-invasive assay using exfoliated cells to detect genetic changes
      present in the lesions was 45% (9 of 20), the specificity was 100% (19 of 19),
      and the positive predictive value was also 100% (9 of 9). LOH was present in 20
      of 39 (51%) of the biopsies with uniformly LOH at 9p. Mutated TP53 and LOH at 9p
      in the biopsy, as single markers and in combination, were significant risk
      factors for malignant progression of leukoplakia to oral cancer (Kaplan-Meier
      analysis, p<0.05). CONCLUSION: A non-invasive genetic screening approach using
      LOH in exfoliated cells has limited value for monitoring patients with
      leukoplakia. However, LOH at 9p, but also mutated TP53 in biopsies of oral
      leukoplakia have a significant association with malignant transformation and are
      promising candidate biomarkers to predict the risk for malignant progression.

PMID- 24120276
TI  - Insulin stimulates progesterone secretion to a greater extent than LH in early
      pregnant buffalo luteal cells cultured in vitro.
AB  - In the present study, effect of insulin alone or in combination with LH on
      modulation of progesterone production by early pregnant buffalo luteal cells was
      reported. Luteal cells were isolated using collagenase and subsequently cultured
      in Ham'F-12 at 37  degrees C in an atmosphere of 5% CO2 and 95% humidified air.
      Small luteal cells (SLC, 12-23 MU) appeared as spindle shaped with eccentrically
      placed irregular nucleus, however, large luteal cells (LLC, 25-55 MU) were
      polyhedral or spherical in shape with centrally placed large round nucleus having
      one or two nucleoli. There was an abundance of cytoplasmic lipid droplets and a
      greater cytoplasmic to nuclear ratio as compared to SLC. Both small and large
      luteal cells were positive to 3 beta-HSD, a marker for steroidogenic capacity.
      Luteal cells attached to surface within 24h of culture and appeared typical of
      epithelial cells with numerous cytoplasmic lipid droplets within the cytoplasm.
      These cells maintained the morphological characteristics throughout the culture
      period. Luteal cells were treated with insulin (0.05 IU/ml) and LH (10 ng/ml)
      alone or in combination for 7 days to study the effect on progesterone
      production. Morphology of luteal cells did not change with the addition of LH and
      insulin. Addition of insulin enhanced (P<0.01) basal as well as LH stimulated
      progesterone production and also minimized loss of cell number by maintaining
      greater cell populations throughout the culture period as compared to control and
      LH treatment. In the absence of tropic stimulation, progesterone secretion
      decreased rapidly in the control group while addition of insulin greatly
      decreased the rate of decline. The findings of the present study reveal insulin
      enhances progesterone secretion by the luteal cells indicating its possible role
      to modulate corpus luteum function in buffalo.

PMID- 24120277
TI  - Model for a flexible motor memory based on a self-active recurrent neural
      network.
AB  - Using recent recurrent network architecture based on the reservoir computing
      approach, we propose and numerically simulate a model that is focused on the
      aspects of a flexible motor memory for the storage of elementary movement
      patterns into the synaptic weights of a neural network, so that the patterns can
      be retrieved at any time by simple static commands. The resulting motor memory is
      flexible in that it is capable to continuously modulate the stored patterns. The
      modulation consists in an approximately linear inter- and extrapolation,
      generating a large space of possible movements that have not been learned before.
      A recurrent network of thousand neurons is trained in a manner that corresponds
      to a realistic exercising scenario, with experimentally measured muscular
      activations and with kinetic data representing proprioceptive feedback. The
      network is "self-active" in that it maintains recurrent flow of activation even
      in the absence of input, a feature that resembles the "resting-state activity"
      found in the human and animal brain. The model involves the concept of "neural
      outsourcing" which amounts to the permanent shifting of computational load from
      higher to lower-level neural structures, which might help to explain why humans
      are able to execute learned skills in a fluent and flexible manner without the
      need for attention to the details of the movement. 

PMID- 24120278
TI  - Impaired visual perception of hurtful actions in patients with chronic low back
      pain.
AB  - Visually presented biological motion stimuli activate regions in the brain that
      are also related to musculo-skeletal pain. We therefore hypothesized that chronic
      pain impairs the perception of visually presented actions that involve body parts
      that hurt. In the first experiment, chronic back pain (CLBP) patients and healthy
      controls judged the lifted weight from point-light biological motion displays. An
      actor either lifted an invisible container (5, 10, or 15 kg) from the floor, or
      lifted and manipulated it from the right to the left. The latter involved
      twisting of the lower back and would be very painful for CLBP patients. All
      participants recognized the displayed actions, but CLBP patients were impaired in
      judging the difference in handled weights, especially for the trunk rotation. The
      second experiment involved discrimination between forward and backward walking.
      Here the patients were just as good as the controls, showing that the main result
      of the first experiment was indeed specific to the sensory aspects of the task,
      and not to general impairments or attentional deficits. The results thus indicate
      that the judgment of sensorimotor aspects of a visually displayed movement is
      specifically affected by chronic low back pain.

PMID- 24120279
TI  - An 18-month follow-up investigation of motor coordination and working memory in
      primary school children.
AB  - The aim of the current study was to examine the relationship between motor
      coordination and visual working memory in children aged 5-11 years. Participants
      were 18 children with movement difficulty and 41 control children, assessed at
      baseline and following an 18-month time period. The McCarron Assessment of
      Neuromuscular Development provided a measure of motor skills and the CogState One
      Back task was used to assess visual working memory. Multi-level mixed effects
      linear regressions were used to assess the relationship between fine motor
      skills, gross motor skills, and visual working memory. The results revealed that
      for children with movement difficulty, better fine motor skills at baseline
      significantly predicted greater One-Back accuracy and greater (i.e., faster)
      speed at 18-month follow-up. Conversely, fine motor skills at baseline did not
      predict One-Back accuracy and speed for control children. However, for both
      groups, greater One-Back accuracy at baseline predicted better fine and gross
      motor skills at follow-up. These findings have important implications for the
      assessment and treatment of children referred for motor difficulties and/or
      working memory difficulties.

PMID- 24120280
TI  - Using dynamic walking models to identify factors that contribute to increased
      risk of falling in older adults.
AB  - Falls are common in older adults. The most common cause of falls is tripping
      while walking. Simulation studies demonstrated that older adults may be
      restricted by lower limb strength and movement speed to regain balance after a
      trip. This review examines how modeling approaches can be used to determine how
      different measures predict actual fall risk and what some of the causal
      mechanisms of fall risk are. Although increased gait variability predicts
      increased fall risk experimentally, it is not clear which variability measures
      could best be used, or what magnitude of change corresponded with increased fall
      risk. With a simulation study we showed that the increase in fall risk with a
      certain increase in gait variability was greatly influenced by the initial level
      of variability. Gait variability can therefore not easily be used to predict fall
      risk. We therefore explored other measures that may be related to fall risk and
      investigated the relationship between stability measures such as Floquet
      multipliers and local divergence exponents and actual fall risk in a dynamic
      walking model. We demonstrated that short-term local divergence exponents were a
      good early predictor for fall risk. Neuronal noise increases with age. It has
      however not been fully understood if increased neuronal noise would cause an
      increased fall risk. With our dynamic walking model we showed that increased
      neuronal noise caused increased fall risk. Although people who are at increased
      risk of falling reduce their walking speed it had been questioned whether this
      slower speed would actually cause a reduced fall risk. With our model we
      demonstrated that a reduced walking speed caused a reduction in fall risk. This
      may be due to the decreased kinematic variability as a result of the reduced
      signal-dependent noise of the smaller muscle forces that are required for slower.
      These insights may be used in the development of fall prevention programs in
      order to better identify those at increased risk of falling and to target those
      factors that influence fall risk most. 

PMID- 24120281
TI  - Diabetes, peripheral neuropathy, and lower-extremity function.
AB  - OBJECTIVE: Diabetes among older adults causes many complications, including
      decreased lower-extremity function and physical disability. Diabetes can cause
      peripheral nerve dysfunction, which might be one pathway through which diabetes
      leads to decreased physical function. The study aims were to determine the
      following: (1) whether diabetes and impaired fasting glucose are associated with
      objective measures of physical function in older adults, (2) which peripheral
      nerve function (PNF) tests are associated with diabetes, and (3) whether PNF
      mediates the diabetes-physical function relationship. RESEARCH DESIGN AND
      METHODS: This study included 983 participants, age 65 years and older from the
      InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical
      performance was assessed using the Short Physical Performance Battery (SPPB),
      scored from 0 to 12 (higher values, better physical function) and usual walking
      speed (m/s). PNF was assessed via standard surface electroneurographic study of
      right peroneal nerve conduction velocity, vibration and touch sensitivity.
      Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to
      5 (higher values, greater neuropathy). Multiple linear regression models were
      used to test associations. RESULTS AND CONCLUSION: One hundred twenty-six (12.8%)
      participants had diabetes. Adjusting for age, sex, education, and other
      confounders, diabetic participants had decreased SPPB (beta=-0.99; p<0.01),
      decreased walking speed (beta=-0.1m/s; p<0.01), decreased nerve conduction
      velocity (beta=-1.7m/s; p<0.01), and increased neuropathy (beta=0.25; p<0.01)
      compared to non-diabetic participants. Adjusting for nerve conduction velocity
      and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting
      partial mediation through decreased PNF.

PMID- 24120283
TI  - How to get your paper published paper: an editor's perspective.

PMID- 24120282
TI  - Physical inactivity affects skeletal muscle insulin signaling in a birth weight
      dependent manner.
AB  - AIMS: We investigated whether physical inactivity could unmask defects in insulin
      and AMPK signaling in low birth weight (LBW) subjects. METHODS: Twenty LBW and 20
      normal birth weight (NBW) subjects were investigated using the euglycemic
      hyperinsulinemic clamp with excision of skeletal muscle biopsies pre and post
      9days of bed rest. Employing Western blotting, we investigated skeletal muscle
      Akt, AS160, GLUT4, and AMPK signaling. RESULTS: Peripheral insulin action was
      similar in the two groups and was decreased to the same extent post bed rest.
      Insulin and AMPK signaling was unaffected by bed rest in NBW individuals. LBW
      subjects showed decreased insulin-stimulated Akt phosphorylation and increased
      AMPK alpha1 and gamma3 protein expression post bed rest. Insulin response of
      AS160 phosphorylation was lower in LBW subjects both pre and post bed rest.
      CONCLUSIONS: Bed rest-induced insulin resistance is not explained by impaired
      muscle insulin or AMPK signaling in subjects with or without LBW. Lower muscle
      insulin signaling in LBW subjects post bed rest despite similar degree of insulin
      resistance as seen in controls may to some extent support the idea that LBW
      subjects are at higher risk of developing type 2 diabetes when being physically
      inactive.

PMID- 24120285
TI  - Coexistence of Langerhans cells activation and immune cells infiltration in
      progressive nonsegmental vitiligo.

PMID- 24120284
TI  - Obligatory roles of filamin A in E-cadherin-mediated cell-cell adhesion in
      epidermal keratinocytes.
AB  - BACKGROUND: Extracellular Ca(2+) (Cao(2+))-induced E-cadherin-mediated cell-cell
      adhesion plays a critical role in promoting differentiation in epidermal
      keratinocytes. Our previous studies show that the calcium-sensing receptor (CaR)
      regulates keratinocyte cell-cell adhesion and differentiation via Rho A-mediated
      signaling. CaR forms a protein complex with Rho A, guanine nucleotide exchange
      factor Trio, and a cytoskeletal actin-binding protein, filamin A, at the cell
      cell junctions in response to elevated Cao(2+) levels. Filamin A has the ability
      to interact directly with CaR, Trio, and Rho and mediate CaR-dependent signaling
      events. OBJECTIVE: This study was conducted to investigate the roles of filamin A
      and Trio in regulating Cao(2+)-induced Rho activation and intercellular adhesion.
      METHODS: Expression of filamin A and Trio in keratinocytes was inhibited by
      siRNA. Its effects on Cao(2+)-dependent junction formation and adhesion complex
      formation were evaluated by fluorescence immunostaining and immunoprecipitation.
      Endogenous Rho activity and expression of keratinocyte differentiation markers
      were also examined. The significance of the physical interactions of filamin A
      with Trio and Rho was assessed in dominant-negative inhibition studies. RESULTS:
      Inhibiting filamin A expression blocked the formation of CaR-Rho A-Trio-E
      cadherin protein complex. Knockdown of filamin A or Trio inhibited Cao(2+)
      induced membrane localization and activation of Rho A, formation of the E
      cadherin-catenin adhesion complex, and keratinocyte terminal differentiation.
      Expressing dominant-negative peptides disruptive to the endogenous filamin-Trio,
      filamin-Rho, and CaR-filamin interactions suppressed the formation of adherens
      junctions. CONCLUSION: Through physical interactions with CaR, Trio and Rho,
      filamin A generates a scaffold for organizing a signaling complex that promotes E
      cadherin-mediated cell-cell adhesion and keratinocyte differentiation.

PMID- 24120286
TI  - [Indications for prophylactic hysterectomy].
AB  - Endometrial cancer is the most common gynecologic cancer in France with an
      incidence in France in 2010, of 6560 new cases and 1900 deaths secondary to
      endometrial cancer. The main risk factors are age, hyperoestrogenic factors and
      hereditary syndroms. Prophylactic hysterectomy could prevent endometrial cancer
      in case of risk factors such as genetic syndroms. Actually, only Lynch syndrome
      is a validate indication and should be discussed in patients older than 40-45
      years. Prophylactic hysterectomy does not seem a reasonable option to patients
      carrying BRCA 1 or 2 mutation. 

PMID- 24120287
TI  - Fetal surgery for neural tube defects.
AB  - A recently completed randomized, controlled, prospective multicenter trial, the
      Management of Myelomeningocele Study (MOMS), demonstrated that maternal-fetal
      surgery for myelomeningocele (MMC) before 26 weeks of gestation decreases the
      need for ventriculoperitoneal shunting, decreases hindbrain herniation, and
      preserves neurological function. However, the study also found that fetal MMC
      surgery is not without significant risks, such as premature delivery or maternal
      complications. The primary objective of this review is to provide a critical
      overview of the rationale for in-utero intervention for MMC in the context of
      pathological observations, animal models, initial clinical experience with human
      fetal MMC surgery, and the results of the randomized trial. The secondary
      objective is to briefly discuss our approach to fetal MMC. Finally, the ongoing
      clinical research and the recent developments of potential alternative fetal
      surgical techniques will be highlighted. 

PMID- 24120288
TI  - Potential of proton-pumping rhodopsins: engineering photosystems into
      microorganisms.
AB  - A wide range of proton-pumping rhodopsins (PPRs) have been discovered in recent
      years. Using a synthetic biology approach, PPR photosystems with different
      features can be easily introduced in nonphotosynthetic microbial hosts. PPRs can
      provide hosts with the ability to harvest light and drive the sustainable
      production of biochemicals or biofuels. PPRs use light energy to generate an
      outward proton flux, and the resulting proton motive force can subsequently power
      cellular processes. Recently, the introduction of PPRs in microbial production
      hosts has successfully led to light-driven biotechnological conversions. In this
      review, we discuss relevant features of natural PPRs, evaluate reported
      biotechnological applications of microbial production hosts equipped with PPRs,
      and provide an outlook on future developments. 

PMID- 24120289
TI  - From candidate genes to genome-wide association: the challenges and promise of
      posttraumatic stress disorder genetic studies.

PMID- 24120290
TI  - Understanding somatic symptom disorder: the role of translational neuroscience.

PMID- 24120291
TI  - The renin-angiotensin system in adipose tissue and its metabolic consequences
      during obesity.
AB  - Obesity is a worldwide disease that is accompanied by several metabolic
      abnormalities such as hypertension, hyperglycemia and dyslipidemia. The
      accelerated adipose tissue growth and fat cell hypertrophy during the onset of
      obesity precedes adipocyte dysfunction. One of the features of adipocyte
      dysfunction is dysregulated adipokine secretion, which leads to an imbalance of
      pro-inflammatory, pro-atherogenic versus anti-inflammatory, insulin-sensitizing
      adipokines. The production of renin-angiotensin system (RAS) components by
      adipocytes is exacerbated during obesity, contributing to the systemic RAS and
      its consequences. Increased adipose tissue RAS has been described in various
      models of diet-induced obesity (DIO) including fructose and high-fat feeding. Up
      regulation of the adipose RAS by DIO promotes inflammation, lipogenesis and
      reactive oxygen species generation and impairs insulin signaling, all of which
      worsen the adipose environment. Consequently, the increase of circulating RAS,
      for which adipose tissue is partially responsible, represents a link between
      hypertension, insulin resistance in diabetes and inflammation during obesity.
      However, other nutrients and food components such as soy protein attenuate
      adipose RAS, decrease adiposity, and improve adipocyte functionality. Here, we
      review the molecular mechanisms by which adipose RAS modulates systemic RAS and
      how it is enhanced in obesity, which will explain the simultaneous development of
      metabolic syndrome alterations. Finally, dietary interventions that prevent
      obesity and adipocyte dysfunction will maintain normal RAS concentrations and
      effects, thus preventing metabolic diseases that are associated with RAS
      enhancement. 

PMID- 24120292
TI  - The nature of social preference and interactions in Smith-Magenis syndrome.
AB  - This natural observation study was designed to evaluate hypothesized elevated
      'attention-seeking' and preference for adult attention in Smith-Magenis syndrome.
      Ten children with Smith-Magenis syndrome were observed across one school day,
      together with an age matched sample of 10 children with Down syndrome. Levels of
      attention given to, and vigilance for, adults and peers were recorded and
      compared. Sequences of behaviour were analyzed to evaluate the temporal
      relationships between giving and receiving attention during adult-child
      interactions. Compared to children with Down syndrome, children with Smith
      Magenis syndrome gave preferential attention to adults and looked towards adults
      significantly more than they looked towards peers. Sequential analyses revealed
      that while children with Smith-Magenis syndrome did not initiate interactions
      with adults more than children with Down syndrome did, reciprocity between child
      and adult social behaviours in Smith-Magenis syndrome within interactions was
      compromised. This less synchronous sequence of child and adult interactions in
      Smith-Magenis syndrome may be the result of children with Smith-Magenis syndrome
      attempting to initiate interaction at times when it is unavailable. The marked
      preference for interacting with adults over peers in Smith-Magenis syndrome
      indicates atypicality of social interaction in this syndrome. 

PMID- 24120294
TI  - Ensuring a global workforce: A challenge and opportunity.

PMID- 24120293
TI  - Super-resolved parallel MRI by spatiotemporal encoding.
AB  - Recent studies described an "ultrafast" scanning method based on spatiotemporal
      (SPEN) principles. SPEN demonstrates numerous potential advantages over EPI-based
      alternatives, at no additional expense in experimental complexity. An important
      aspect that SPEN still needs to achieve for providing a competitive ultrafast MRI
      acquisition alternative, entails exploiting parallel imaging algorithms without
      compromising its proven capabilities. The present work introduces a combination
      of multi-band frequency-swept pulses simultaneously encoding multiple, partial
      fields-of-view, together with a new algorithm merging a Super-Resolved SPEN image
      reconstruction and SENSE multiple-receiving methods. This approach enables one to
      reduce both the excitation and acquisition times of sub-second SPEN acquisitions
      by the customary acceleration factor R, without compromises in either the
      method's spatial resolution, SAR deposition, or capability to operate in multi
      slice mode. The performance of these new single-shot imaging sequences and their
      ancillary algorithms were explored and corroborated on phantoms and human
      volunteers at 3 T. The gains of the parallelized approach were particularly
      evident when dealing with heterogeneous systems subject to major T2/T2* effects,
      as is the case upon single-scan imaging near tissue/air interfaces.

PMID- 24120295
TI  - [Evolution of waiting time and length of stay between 2005 and 2012 in an
      obstetric and gynaecologic emergency unit in a French teaching hospital].
AB  - OBJECTIVES: To compare and analyze waiting time and length of stay between 2005
      and 2012 in the obstetric and gynaecologic emergency unit of Nantes teaching
      hospital, new unit opened in 2004. METHODS: Descriptive study from the registers
      over 2months' periods in 2005 and 2012. RESULTS: Despite an increase of the daily
      average number of visits from 28 to 39 (P<0.0001), the waiting time increased in
      obstetrics from 15minutes to 18 in 2012, P<0.03. In gynaecology, waiting time
      decreased in 2012 on daytime weekdays (37minutes versus 44) and increased on
      weekend (41minutes versus 28) and at night (37minutes versus 23) P<0.01. The
      length of stay was similar in obstetrics (108minutes versus 104) but reduced on
      daytime weekdays (124minutes in 2005, 109 in 2012, P<0.05). In gynaecology
      duration was similar (108minutes versus 105), but decreased on daytime weekdays
      (110minutes in 2005, 101 in 2012) and increased on overnight weekend (94minutes
      in 2005, 121 in 2012) (P<0.05). CONCLUSION: Our organization enabled to improve
      some lengths of time despite an increased activity. Those lengths of time should
      be monitored as they reflect our organizations and are indicators of efficiency.

PMID- 24120296
TI  - von Baer's law for the ages: lost and found principles of developmental
      evolution.
AB  - In 1828, Karl Ernst von Baer formulated a series of empirically defined rules,
      which became widely known as the 'Law of Development' or 'von Baer's law of
      embryology'. This was one the most significant attempts to define the principles
      that connected morphological complexity and embryonic development. Understanding
      this relation is central to both evolutionary biology and developmental genetics.
      Von Baer's ideas have been both a source of inspiration to generations of
      biologists and a target of continuous criticism over many years. With advances in
      multiple fields, including paleontology, cladistics, phylogenetics, genomics, and
      cell and developmental biology, it is now possible to examine carefully the
      significance of von Baer's law and its predictions. In this review, I argue that,
      185 years after von Baer's law was first formulated, its main concepts after
      proper refurbishing remain surprisingly relevant in revealing the fundamentals of
      the evolution-development connection, and suggest that their explanation should
      become the focus of renewed research. 

PMID- 24120297
TI  - Conjugates of a secoiridoid glucoside with a phenolic glucoside from the flower
      buds of Lonicera japonica Thunb.
AB  - Secoiridoid glucosides, including two conjugates with a phenolic and two
      conjugates with a nicotinic acid derivative (3 and 4), together with seven known
      secoiridoid derivatives, were isolated from flower buds of Lonicera japonica. The
      structures were elucidated by spectroscopic analyses. Anti-influenza activities
      of six isolated compounds were also evaluated by plaque assay and neuraminidase
      inhibitory assay. 

PMID- 24120298
TI  - Cancer chemopreventive diterpenes from Salvia corrugata.
AB  - NMR and NP-HPLC-UV profiling of the exudate of Salvia corrugata revealed that its
      secondary metabolite composition was largely dominated by alpha-hydroxy-beta
      isopropyl-benzoquinone diterpenoids. Among them, four diterpenes not described
      previously were isolated and identified as fruticulin C (3), 7alpha-methoxy-19
      acetoxy-royleanone (4), 7alpha,19-diacetoxy-royleanone (5), and 7-dehydroxy
      conacytone (7). In addition, the known diterpenes fruticulin A (1), demethyl
      fruticulin A (2) and 7alpha-O-methyl-conacytone (6) were also obtained. The
      isolated compounds were evaluated for their cancer chemopreventive activity by
      measuring quinone reductase induction activity and histone deacetylase
      inhibition. Three compounds (1, 2 and 5) showed promising activity. 

PMID- 24120299
TI  - Isolation of natural compounds from Phlomis stewartii showing alpha-glucosidase
      inhibitory activity.
AB  - Stewartiiside (1), a phenylethanoid glycoside and three 28-nortriterpenoids:
      stewertiisins A-C [(17R)-19(18->17)-abeo-3alpha,18beta,23,24-tetrahydroxy-28
      norolean-12-ene, 2; (17R)-19(18->17)-abeo-2alpha,16beta,18beta,23,24-pentahydroxy
      28-norolean-12-en-3-one, 3; (17R)-19(18->17)-abeo-2alpha,3alpha,23,24
      tetrahydroxy-28-noroleane-11,13-diene, 4] together with eight known compounds:
      lunariifolioside (5), notohamosin A (6), phlomispentanol (7), isorhamnetin 3-(6-p
      coumaroyl)-beta-D-glucopyranoside (8), tiliroside (9), caffeic acid (10), p
      hydrxybenzoic acid (11) and oleanolic acid (12) were isolated from the ethyl
      acetate soluble fraction of the methanolic extract of whole plant of Phlomis
      stewartii. The structures of these isolates (1-12) were elucidated by the
      combination of 1D ((1)H and (13)C NMR), 2D (HMQC, HMBC COSY, NOESY) NMR
      spectroscopy and mass spectrometry (EIMS, HREIMS, FABMS, HRFABMS) and in
      comparison with literature data of related compounds. All the isolates (1-12)
      showed alpha-glucosidase inhibitory activity with IC50 values ranging between
      14.5 and 355.4 MUM, whereas, compounds 1, 5, 9 and 10 showed promising alpha
      glucosidase inhibitory activity with IC50 values below 30 MUM.

PMID- 24120300
TI  - Mechanisms for regulation of plant kinesins.
AB  - Throughout the eukaryotic world, kinesins serve as molecular motors for the
      directional transport of cellular cargo along microtubule tracks. Plants contain
      a large number of kinesins that have conserved as well as specialized functions.
      These functions depend on mechanisms that regulate when, where and what kinesins
      transport. In this review, we highlight recent studies that have revealed
      conserved modes of regulation between plant kinesins and their non-photosynthetic
      counterparts. These findings lay the groundwork for understanding how plant
      kinesins are differentially engaged in various cellular processes that underlie
      plant growth and development. 

PMID- 24120301
TI  - Schizophrenia thalamus imaging: low benzamide binding to dopamine D2 receptors
      suggests fewer D2Short receptors and fewer presynaptic terminals.
AB  - The dopamine D2 receptor continues to be the major target for the treatment of
      schizophrenia and is one of many genes genetically associated with this disease.
      Recent data show that fewer short forms of the D2 receptor protein are
      synthesized if there is a genetic variant in the D2 receptor (with a T in rs
      1076560 in intron 6). At the same time, at least six publications report that the
      binding of radioactive benzamides is reduced in the schizophrenia thalamus. A
      review of the benzamide pharmacology of the short and long forms of the D2
      receptor shows that benzamides have a 2.4-fold higher affinity for the D2Short
      receptor relative to the D2Long form. Hence, the reduced amount of benzamide
      binding to the D2 receptors in the schizophrenia thalamus suggests that there is
      a reduced amount of D2Short receptors in this diseased region, and may possibly
      also mean fewer presynaptic terminals because that is where D2Short receptors
      mostly reside. If so, fewer presynaptic dopamine terminals in various brain
      regions may be the basis of the known behavioural dopamine supersensitivity in
      schizophrenia. 

PMID- 24120302
TI  - Impaired context processing as a potential marker of psychosis risk state.
AB  - While structural abnormalities of the dorsolateral prefrontal cortex (DLPFC) may
      pre-date and predict psychosis onset, the relationships between functional
      deficits, cognitive and psychosocial impairments has yet to be explored in the at
      risk period. An established measure of cognitive control (AXCPT) was administered
      to demographically matched clinical-high-risk (CHR; n=25), first-episode
      schizophrenia (FE; n=35), and healthy control (HC; n=35) participants during
      functional magnetic resonance imaging (fMRI) to investigate these relationships.
      CHR and FE individuals demonstrated impaired context processing and reduced DLPFC
      activation relative to HC individuals during increased cognitive control demands.
      FE and CHR individuals' ability to increase DLPFC activity in response to
      cognitive control demands was associated with better task performance. Task
      performance was also associated with severity of disorganization and poverty
      symptoms in FE participants. These findings support more extensive studies using
      fMRI to examine the clinical significance of prefrontal cortical functioning in
      the earliest stages of psychosis. 

PMID- 24120303
TI  - Subcortical modulation of attentional control by second-generation antipsychotics
      in first-episode psychosis.
AB  - Psychotic disorders are characterized by significant deficits in attentional
      control, but the neurobiological mechanisms underlying these deficits early in
      the course of illness prior to extensive pharmacotherapy are not well understood.
      Moreover, little is known regarding the symptom and brain changes associated with
      amelioration of attentional impairments through antipsychotic pharmacotherapy. In
      this study 14 male patients experiencing a first-episode of psychosis with
      minimal prior antipsychotic treatment completed an attentional control task while
      undergoing functional magnetic resonance imaging at the onset of treatment with a
      second generation antipsychotic (risperidone or aripiprazole) in a double blind
      randomized clinical trial and then again following approximately 12 weeks of
      treatment. In addition, 14 age-, and performance-matched healthy male volunteers
      who were not treated completed the same task at a baseline timepoint and then
      again following 12 weeks. Patients showed significantly greater activation than
      healthy volunteers in the right globus pallidus, left thalamus, and right
      thalamus at the time of the baseline scan. Among patients there was a significant
      reduction in right globus pallidus blood-oxygen level dependent (BOLD) response
      following antipsychotic treatment that correlated significantly with improvement
      in response accuracy and reductions in thought disturbance. No changes in globus
      pallidus activation were observed in healthy volunteers over this time period.
      These preliminary findings suggest that improvement in attentional control and
      concomitant reductions in thought disturbance in first-episode psychosis may be
      associated with reductions in subcortical activity following administration of
      second-generation antipsychotics early in the course of illness. These findings
      have implications for understanding how changes in basal ganglia activity may be
      linked to improvements in attentional control through antipsychotics. 

PMID- 24120304
TI  - Analysis of mitochondrial DNA HVR1 haplotype of pure-bred domestic dogs in Japan.
AB  - To develop DNA markers for forensic analysis, we examined the hypervariable
      region 1 (HVR1) sequences of 447 pure-bred domestic dogs (Canis lupus familiaris)
      that had been bred and raised in Japan. HVR1 is a 660-bp stretch of mitochondrial
      (mt) DNA. Among the 447 HVR1 sequences examined, we identified 58 haplotypes from
      47 single nucleotide polymorphisms (SNPs) and two insertion-deletion (InDel)
      polymorphisms. The haplotype diversity inferred from inter-breed analysis (N=154,
      88 breeds) was 0.929+/-0.011. Intra-breed analysis showed that the haplotype
      diversity of Golden Retrievers (N=53), Labrador Retrievers (N=67), Miniature
      Dachshunds (N=61), Toy Poodles (N=62), and Welsh Corgis (N=50) was 0.624+/-0.052,
      0.722+/-0.029, 0.922+/-0.010, 0.877+/-0.020, and 0.443+/-0.084, respectively. The
      results of this genotype analysis were used to construct a dataset consisting of
      dog mtDNA HVR1 sequences for use in forensic applications in Japan. 

PMID- 24120305
TI  - Arterial switch operation for transposition of the great arteries with anomalies
      of cardiac situs and aortic position.

PMID- 24120306
TI  - Colourful indocyanine green lymphography.

PMID- 24120307
TI  - Levels, profile and distribution of Dechloran Plus (DP) and Polybrominated
      Diphenyl Ethers (PBDEs) in the environment of Pakistan.
AB  - No scientific data is available on emerging contaminants including Polybrominated
      Diphenyl Ethers (PBDEs) and Dechloran Plus (DP) levels in the environment in
      Pakistan. Levels of PBDEs and DP were determined in the soil, sediment and
      atmospheric samples along the stretch of River Ravi in Punjab Province. Average
      concentrations of SigmaPBDEs in atmosphere, soils and sediments were 36 pg m(-3),
      40 ng g(-1) and 640 ng g(-1). BDE-209 was the most abundant PBDE congener,
      showing that deca-BDE accounts for most of the total PBDE emitted in the
      environment of Pakistan. Total DP levels were calculated as 88 pg m(-3), 0.8 ng
      g(-1) and 1.9 ng g(-1) in air, soil and sediment samples, respectively. The lower
      average fractions of anti-DP showed significant differences to those of the
      technical mixtures, indicating the lack of DP production source in Pakistan.

PMID- 24120308
TI  - Recommendations for fitness for work medical evaluations in chronic respiratory
      patients. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR).
AB  - Chronic respiratory diseases often cause impairment in the functions and/or
      structure of the respiratory system, and impose limitations on different
      activities in the lives of persons who suffer them. In younger patients with an
      active working life, these limitations can cause problems in carrying out their
      normal work. Article 41 of the Spanish Constitution states that "the public
      authorities shall maintain a public Social Security system for all citizens
      guaranteeing adequate social assistance and benefits in situations of hardship".
      Within this framework is the assessment of fitness for work, as a dual-nature
      process (medico-legal) that aims to determine whether it is appropriate or not to
      recognise a person's right to receive benefits which replace the income that they
      no longer receive as they cannot carry out their work, due to loss of health. The
      role of the pulmonologist is essential in evaluating the diagnosis, treatment,
      prognosis and functional capacity of respiratory patients. These recommendations
      seek to bring the complex setting of fitness for work evaluation to
      pulmonologists and thoracic surgeons, providing action guidelines that allow them
      to advise their own patients about their incorporation into working life. 

PMID- 24120309
TI  - High-impact strength acrylic denture base material processed by autoclave.
AB  - PURPOSE: To investigate the effect of two different cycles of autoclave
      processing on the transverse strength, impact strength, surface hardness and the
      porosity of high-impact strength acrylic denture base material. METHODS: High
      Impact Acryl was the heat-cured acrylic denture base material included in the
      study. A total of 120 specimens were prepared, the specimens were grouped into:
      control groups in which high-impact strength acrylic resins processed by
      conventional water-bath processing technique (74 degrees C for 1.5 h then boil
      for 30 min) and experimental groups in which high-impact strength acrylic resins
      processed by autoclave at 121 degrees C, 210 kPa .The experimental groups were
      divided into (fast) groups for 15 min, and (slow) groups for 30 min. To study the
      effect of the autoclave processing (Tuttnauer 2540EA), four tests were conducted
      transverse strength (Instron universal testing machine), impact strength (Charpy
      tester), surface hardness (shore D), and porosity test. The results were analyzed
      to ANOVA and LSD test. RESULTS: In ANOVA test, there were highly significant
      differences between the results of the processing techniques in transverse,
      impact, hardness, and porosity test. The LSD test showed a significant difference
      between control and fast groups in transverse and hardness tests and a non
      significant difference in impact test and a highly significant difference in
      porosity test; while, there were a highly significant differences between control
      and slow groups in all examined tests; finally, there were a non-significant
      difference between fast and slow groups in transverse and porosity tests and a
      highly significant difference in impact and hardness tests. CONCLUSIONS: In the
      autoclave processing technique, the slow (long) curing cycle improved the tested
      physical and mechanical properties as compared with the fast (short) curing
      cycle. The autoclave processing technique improved the tested physical and
      mechanical properties of High Impact Acryl.

PMID- 24120310
TI  - Phytochemical identity and stability of herbal products: challenges for clinical
      research.

PMID- 24120311
TI  - Tackling fuel poverty through facilitating energy tariff switching: a
      participatory action research study in vulnerable groups.
AB  - OBJECTIVES: A fifth of UK households live in fuel poverty, with significant
      health risks. Recent government strategy integrates public health with local
      government. This study examined barriers to switching energy tariffs and the
      impact of an energy tariff switching 'intervention' on vulnerable peoples'
      likelihood to, success in, switching tariffs. STUDY DESIGN: Participatory Action
      Research (PAR), conducted in West London. METHODS: Community researchers from
      three voluntary/community organisations (VCOs) collaborated in recruitment, study
      design, data collection and analysis. VCOs recruited 151 participants from
      existing service users in three groups: Black and Minority Ethnic (BME)
      communities, older people (>75 yrs) and families with young children. Researchers
      conducted two semi-structured interviews with each participant, a week apart. The
      first interview asked about demographics, current energy supplier, financial
      situation, previous experience of tariff-switching and barriers to switching.
      Researchers then provided the 'intervention' - advice on tariff-switching,
      printed materials, access to websites. The second interview explored usefulness
      of the 'intervention', other information used, remaining barriers and information
      needs. Researchers kept case notes and a reflective log. Data was analysed
      thematically and collaboratively between the research coordinator and
      researchers. Quantitative data was analysed using SPSS, with descriptive
      statistics and Chi-squared tests. A total of 151 people were interviewed: 47
      older people over 75 years, 51 families with young children, 51 BME (two were
      missing demographics). RESULTS: The majority were not White British or UK-born.
      Average household weekly income was L230. Around half described 'difficult'
      financial situations, 94% were receiving state benefits and 62% were in debt.
      Less than a third had tried to find a better energy deal; knowledge was the main
      barrier. After the intervention 19 people tried to switch, 13 did. Young families
      were most likely to switch, older people least. The main reasons for not
      switching were apathy ('can't be bothered'), lack of time, fear or scepticism and
      loyalty. Older people were particularly affected by apathy and scepticism. The
      personalized advice and help with websites was especially valued. CONCLUSIONS:
      Low-income consumers appear to have considerable apathy to switching energy
      tariffs, despite potential savings and health benefits, in part due to their
      complex lives in which switching is not a priority. An independent, one-on-one,
      personalized 'intervention' encouraged switching, particularly for young
      families. However, older people still experience significant barriers to
      switching with specific interventions needed, which take account of their status
      quo bias, energy use habits and scepticism. The recent integration of public
      health and local government in the UK may provide the ideal environment for
      providing similar services which are desperately needed to reduce fuel poverty in
      these groups in line with the new Public Health Strategy.

PMID- 24120313
TI  - Unidirectional visual motion adaptation induces reciprocal inhibition of human
      early visual cortex excitability.
AB  - OBJECTIVES: Behavioural observations provided by the waterfall illusion suggest
      that motion perception is mediated by a comparison of responsiveness of
      directional selective neurones. These are proposed to be optimally tuned for
      motion detection in different directions. Critically however, despite the
      behavioural observations, direct evidence of this relationship at a cortical
      level in humans is lacking. By utilising the state dependant properties of
      transcranial magnetic stimulation (TMS), one can probe the excitability of
      specific neuronal populations using the perceptual phenomenon of phosphenes.
      METHOD: We exposed subjects to unidirectional visual motion adaptation and
      subsequently simultaneously measured early visual cortex (V1) excitability whilst
      viewing motion in the adapted and non-adapted direction. RESULT: Following
      adaptation, the probability of perceiving a phosphene whilst viewing motion in
      the adapted direction was diminished reflecting a reduction in V1 excitability.
      Conversely, V1 excitability was enhanced whilst viewing motion in the opposite
      direction to that used for adaptation. CONCLUSION: Our results provide support
      that in humans a process of reciprocal inhibition between oppositely tuned
      directionally selective neurones in V1 facilitates motion perception.
      SIGNIFICANCE: This paradigm affords a unique opportunity to investigate changes
      in cortical excitability following peripheral vestibular disorders.

PMID- 24120314
TI  - Determining optimal rTMS parameters through changes in cortical inhibition.
AB  - OBJECTIVES: Evidence shows that repetitive transcranial magnetic stimulation
      (rTMS) changes cortical inhibition (CI) and excitability and that these changes
      may relate to its therapeutic effects. This study aimed to investigate the
      effects of differing durations or 'doses' of rTMS on cortical inhibition and
      excitability in healthy subjects. METHODS: Four different experiments were
      conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10
      sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of
      3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz
      active or sham rTMS. Measures of cortical inhibition and excitability included
      short-interval intracortical inhibition, long interval cortical inhibition,
      cortical silent period (CSP), motor evoked potential amplitude, resting motor
      threshold and intracortical facilitation. RESULTS: Only 6000 pulses of 20 Hz rTMS
      lead to a significant lengthening of the CSP and therefore potentiation of CI.
      There were no changes to excitability measures. CONCLUSION: Only high frequency
      rTMS potentiated CI. Longer treatment durations are required to produce such
      changes. SIGNIFICANCE: Studies investigating the therapeutic effects of rTMS may
      benefit from extended dosing with increased number of pulses per session. CSP
      lengthening may be used to guide treatment response.

PMID- 24120312
TI  - Structural investigation of a viral ortholog of human NEIL2/3 DNA glycosylases.
AB  - Assault to DNA that leads to oxidative base damage is repaired by the base
      excision repair (BER) pathway with specialized enzymes called DNA glycosylases
      catalyzing the first step of this pathway. These glycosylases can be categorized
      into two families: the HhH superfamily, which includes endonuclease III (or Nth),
      and the Fpg/Nei family, which comprises formamidopyrimidine DNA glycosylase (or
      Fpg) and endonuclease VIII (or Nei). In humans there are three Nei-like (NEIL)
      glycosylases: NEIL1, 2, and 3. Here we present the first crystal structure of a
      viral ortholog of the human NEIL2/NEIL3 proteins, Mimivirus Nei2 (MvNei2),
      determined at 2.04A resolution. The C-terminal region of the MvNei2 enzyme
      comprises two conserved DNA binding motifs: the helix-two-turns-helix (H2TH)
      motif and a C-H-C-C type zinc-finger similar to that of human NEIL2. The N
      terminal region of MvNei2 is most closely related to NEIL3. Like NEIL3, MvNei2
      bears a valine at position 2 instead of the usual proline and it lacks two of the
      three conserved void-filling residues present in other members of the Fpg/Nei
      family. Mutational analysis of the only conserved void-filling residue methionine
      72 to alanine yields an MvNei2 variant with impaired glycosylase activity.
      Mutation of the adjacent His73 causes the enzyme to be more productive thereby
      suggesting a plausible role for this residue in the DNA lesion search process. 

PMID- 24120315
TI  - Trends in the first antiepileptic drug prescribed for epilepsy between 2000 and
      2010.
AB  - PURPOSE: To investigate changes in the choice of first anti-epileptic drug (AED)
      and co-prescription of folic acid after a new diagnosis of epilepsy. METHODS: We
      searched anonymised electronic primary care records dating between 2000 and 2010
      for patients with a new diagnosis of epilepsy and recorded the first AED
      prescribed and whether folic acid was co-prescribed. RESULTS: From 13.3 million
      patient years of primary care records, we identified 3714 patients with a new
      diagnosis of epilepsy (925 children and 649 women aged 14-45 years). Comparing
      first time AED prescriptions in 2000 and 2001 to those in 2009 and 2010 showed a
      significant decrease in the proportion of carbamazepine and phenytoin prescribed
      and a significant increase in the proportion of lamotrigine and levetiracetam
      prescribed. In women aged 14-45 years, and girls aged <18 there was a significant
      decrease in the proportion of sodium valproate prescribed. Women aged 14-45 years
      were significantly more likely to be co-prescribed folic acid with their first
      AED compared to all other patients (20% vs 3%, p-value<0.001). The proportion of
      folic acid co-prescribed with the first AED did not change significantly between
      2000 and 2010. CONCLUSION: The changing trends in the first AED prescribed over
      the last decade, particularly in women of childbearing age, reflect published
      evidence in terms of AED efficacy, tolerability and safety.

PMID- 24120316
TI  - The right to life in a suicidal state.
AB  - This paper considers when the State must take positive steps to protect the right
      to life of a suicidal patient. Using recent developments across the Council of
      Europe which challenge the traditional 'ugly Samaritan' approach of many common
      law systems, it contends that whenever and wherever public authorities know or
      ought to know of a real and immediate risk to the life of an identifiable person,
      they must take reasonable precautions to minimise it. Even J. S. Mill's approach
      to liberty, it is suggested, would tolerate this limited degree of State
      interference. However, notions of autonomy and dignity, the unpredictability of
      human behaviour, and the need to avoid unduly burdening the State must influence
      what it means to act reasonably. 

PMID- 24120317
TI  - Quantification of the variability associated with repeat measurements of left
      ventricular two-dimensional global longitudinal strain in a real-world setting.
AB  - BACKGROUND: Global longitudinal strain (GLS) derived from two-dimensional speckle
      tracking is an emerging technology, but lack of industry standards limits its
      application. Prior studies support using this tool to identify subclinical
      disease through serial changes, but the variability introduced by a change in
      vendor or reader is not well defined. METHODS: Fifty study subjects were
      prospectively identified to include four subgroups to ensure a broad range of
      GLS: normal (n = 20), left ventricular hypertrophy (n = 10), ST-segment elevation
      myocardial infarction (n = 10), and systolic heart failure (n = 10). Raw data
      were obtained using equipment from two vendors during the same session, and GLS
      was analyzed using an offline workstation. Intraobserver and interobserver
      variation was measured using correlation coefficients, intraclass correlation
      coefficients, and Bland-Altman plots. RESULTS: GLS measurements were highly
      reproducible by the same reader or a different reader using vendor 1 and vendor 2
      or comparing vendors (correlation coefficients and intraclass correlation
      coefficients >= 0.95). However, the Bland-Altman plots suggested that the
      variation in repeat GLS measurements may range from +/- 2% to +/- 5% on the basis
      of a change in vendor, reader, or both. CONCLUSIONS: The expected variation in
      GLS measurements associated with a change in vendor, reader, or both should be
      considered when making conclusions about significant changes in serial
      measurements.

PMID- 24120318
TI  - Systemic venous diameters, collapsibility indices, and right atrial measurements
      in normal pediatric subjects.
AB  - BACKGROUND: Compromise of right heart function is an important feature of many
      forms of congenital heart disease, and right atrial (RA) pressure is clinically
      relevant. Inferior vena cava (IVC) diameter and inspiratory collapse are indices
      of RA pressure, but pediatric data are lacking. METHODS: RA measurements,
      systemic venous diameters, and Doppler filling fractions were prospectively
      investigated in healthy volunteer children and adolescents. The IVC was measured
      in its long axis just above the junction with the hepatic veins in the subxiphoid
      view and the superior vena cava at its junction with the right atrium in the
      right parasternal view. The changes in IVC diameter (IVCD) during quiet
      respiration and with a sniff were recorded. Hepatic venous systolic filling
      fraction was calculated from Doppler velocities in the first hepatic vein. RA
      major-axis length, area, and volume were measured from the apical four-chamber
      view. Three measurements of each parameter were averaged over at least three
      respiratory cycles. The IVC collapsibility index (IVCCI) was calculated as
      [(IVCDmax - IVCDmin)/IVCDmax] * 100. Substituting IVCDsniff for IVCDmin in the
      formula, the IVCCIsniff was calculated. RESULTS: Of 132 subjects enrolled, data
      in 120 (mean age, 8.3 +/- 4.5 years) were analyzed. The maximal (expiratory) and
      minimal (inspiratory) diameters during free breathing were 12.1 +/- 3.8 and 8.9
      +/- 3.8 mm for the IVC and 11.9 +/- 3.4 and 7.9 +/- 2.6 mm for the superior vena
      cava. IVCCImin and IVCCIsniff were 30 +/- 13 and 47 +/- 18, respectively. The RA
      major-axis length, area, and indexed maximal volume were 3.7 +/- 0.7 cm, 10.3 +/-
      3.6 cm(2), and 22.3 +/- 7.0 mL/m(2), respectively. Correlations of maximal
      superior vena cava and IVC dimensions with body surface area were slightly better
      than with age and much stronger than with RA volume. No significant correlation
      was found between IVCCIs and age, gender, or indexed RA volume. CONCLUSIONS:
      Measurement of systemic venous diameters, collapsibility indices, and RA volumes
      is feasible in healthy children and adolescents. Venous diameters increase
      predictably with growth and so must be interpreted in light of body surface area.
      IVCCIs and hepatic venous filling fraction compare closely with those reported in
      adults. Pediatric nomograms for these parameters are provided, and they should
      next be evaluated for relation to directly measured RA pressure in this age
      group.

PMID- 24120319
TI  - Right ventricular myocardial performance index derived from tissue Doppler
      echocardiography is useful in differentiating apical ballooning syndrome from
      cardiomyopathy due to left anterior descending coronary artery disease.
AB  - BACKGROUND: Apical ballooning syndrome (ABS) and obstructive coronary artery
      disease of the left anterior descending coronary artery (LAD) can both result in
      similar left ventricular apical wall motion abnormalities. The right ventricle
      may more likely be involved in ABS, and its careful evaluation may help
      differentiate the two conditions. Therefore, the aim of this study was to
      determine the roles of echocardiographic measures of right ventricular (RV)
      function, namely, Doppler tissue imaging-derived RV index of myocardial
      performance (RIMP), RV basal free wall systolic excursion velocity (RV S'), and
      tricuspid annular plane systolic excursion, in differentiating ABS from
      obstructive LAD disease. METHODS: A total of 80 patients with new extensive
      apical left ventricular wall motion abnormalities on echocardiography who
      underwent coronary angiography were identified retrospectively. Patients with
      insufficient echocardiographic data were excluded (n = 17). Admission clinical
      and echocardiographic data were compared between patients with obstructive
      disease of the LAD (LAD group; n = 46) and those with normal coronary arteries
      (ABS group; n = 17). RESULTS: The ABS group had significantly greater RIMP (1.03
      +/- 0.22 vs 0.44 +/- 0.18, P < .001). In predicting ABS, RIMP > 0.74 had
      sensitivity of 94%, specificity of 94%, positive predictive value of 84%, and
      negative predictive value of 98%, with excellent discriminatory ability (area
      under the receiver operating characteristic curve, 0.96 +/- 0.03). Other measures
      of RV function (i.e., tricuspid annular plane systolic excursion and RV S') were
      similar between the two groups. CONCLUSIONS: Doppler tissue imaging-derived RIMP
      may help differentiate ABS from obstructive LAD disease with high accuracy. This
      easily obtainable measurement may offer a noninvasive tool to differentiate these
      two conditions.

PMID- 24120320
TI  - Bio-inspired encapsulation and functionalization of living cells with artificial
      shells.
AB  - In nature, most single cells do not have structured shells to provide extensive
      protection apart from diatoms and radiolarians. Fabrication of biomimetic
      structures based on living cells encapsulated with artificial shells has a great
      impact on the area of cell-based sensors and devices as well as fundamental
      studies in cell biology. The past decade has witnessed a rapid increase of
      research concerning the new fabrication strategies, functionalization and
      applications of this kind of encapsulated cells. In this review, the latest
      fabrication strategies on how to encapsulate living cells with functional shells
      based on the diversity of artificial shells are discussed: hydrogel matrix
      shells, sol-gel shells, polymeric shells, and induced mineral shells. Classical
      different types of artificial shells are introduced and their advantages and
      disadvantages are compared and explained. The biomedical applications of
      encapsulated cells with particular emphasis on cell implant protection, cell
      separation, biosensors, cell therapy and tissue engineering are also described
      and a recap of this review and the future perspectives on these active areas is
      given finally. 

PMID- 24120321
TI  - Myoclonic head jerks and extensor axial dystonia in the variant form of ataxia
      telangiectasia.

PMID- 24120322
TI  - N-terminal pro-B-type natriuretic peptide should be used in all dyspneic patients
      in the ED.

PMID- 24120323
TI  - Myasthenia gravis and Guillain-Barre cooccurrence syndrome.

PMID- 24120324
TI  - Cost-effectiveness of femtosecond laser-assisted cataract surgery versus
      phacoemulsification cataract surgery.
AB  - PURPOSE: To perform a comparative cost-effectiveness analysis (CEA) of
      femtosecond laser-assisted cataract surgery (LCS) and conventional
      phacoemulsification cataract surgery (PCS) DESIGN: Retrospective CEA using
      computer-based econometric modeling. PARTICIPANTS: Hypothetical cohort of
      patients undergoing cataract surgery in the better eye based on a review of the
      current literature and our direct experience using LCS. METHODS: A cost
      effectiveness decision tree model was constructed to analyze the cost
      effectiveness of LCS compared with PCS. Complication rates of cataract surgery
      were obtained from a review of the current literature to complete the cohort of
      patients and outcomes. This data was incorporated with time trade-off utility
      values converted from visual acuity outcomes. MAIN OUTCOME MEASURES: Improvements
      in best-corrected visual acuity obtained from the literature were used to
      calculate the increase in quality-adjusted life-years (QALYs) in a hypothetical
      cohort between 6 months and 1 year after cataract surgery. This was combined with
      approximate costs in a cost-utility analysis model to determine the incremental
      cost-effectiveness ratios (ICERs). RESULTS: Based on the simulated complication
      rates of PCS and LCS and assuming resultant visual acuity outcome improvement of
      5% in uncomplicated cases of LCS, the cost-effectiveness (dollars spent per QALY)
      gained from LCS was not cost-effective at $92 862 Australian Dollars. The total
      QALY gain for LCS over PCS was 0.06 units. Multivariate sensitivity analyses
      revealed that LCS would need to significantly improve visual outcomes and
      complications rates over PCS, along with a reduction in cost to patient, to
      improve cost effectiveness. Modeling a best-case scenario of LCS with excellent
      visual outcomes (100%), a significant reduction in complications (0%) and a
      significantly reduced cost to patient (of $300) resulted in an ICER of $20 000.
      CONCLUSIONS: Laser cataract surgery, irrespective of potential improvements in
      visual acuity outcomes and complication rates, is not cost effective at its
      current cost to patient when compared with cost-effectiveness benchmarks and
      other medical interventions, including PCS. A significant reduction in the cost
      to patient (via reduced consumable/click cost) would increase the likelihood of
      LCS being considered cost effective.

PMID- 24120325
TI  - Imaging of the macula indicates early completion of structural deficit in
      autosomal-dominant optic atrophy.
AB  - PURPOSE: Optical coherence tomography (OCT) enables 3-dimensional imaging of the
      retina, including the layer of ganglion cells that supplies the optic nerve with
      its axons. We tested OCT as means of diagnosing and phenotyping autosomal
      dominant optic atrophy (ADOA). DESIGN: Cross-sectional study. PARTICIPANTS: The
      study included 49 patients with OPA1 exon 28 (2826delT) ADOA (age, 8.6-71.5
      years; best-corrected visual acuity [BCVA], 20/700-20/20) and 51 mutation-free
      first-degree relatives as healthy controls (BCVA 20/25-20/10). METHODS:
      Participants underwent routine examination, including automated perimetry, and
      OCT with segmentation of the perifoveal retinal ganglion cell-inner plexiform
      layer (GC-IPL) and the peripapillary retinal nerve fiber layer (RNFL). MAIN
      OUTCOME MEASURES: Perifoveal GC-IPL thickness. RESULTS: All subjects with ADOA
      had a thinner GC-IPL in the inferonasal macula than the thinnest healthy control.
      The GC-IPL thickness was also subnormal in the superotemporal macula (P<0.0001),
      where it varied with visual acuity (P <= 0.03). Attenuation of the peripapillary
      nerve fiber layer was prominent on the temporal side of the optic disc in ADOA (P
      <0.0001), but there was considerable overlap with healthy controls. In ADOA,
      there was no detectable variation with age in BCVA, autoperimetry mean deviation,
      GC-IPL thickness, or RNFL thickness, except that the thickness of the superior
      RNFL quadrant decreased with age. CONCLUSIONS: Optical coherence tomography
      enabled a highly sensitive diagnosis of ADOA and identification of a structural
      correlate with the variation in visual acuity. The defect associated with the
      OPA1 exon 28 (2826delT) seems to be fully developed from early childhood or the
      perinatal period.

PMID- 24120326
TI  - Impact of hospital volume and specialization on the cost of orbital trauma care.
AB  - PURPOSE: To examine the impact of hospital volume and specialization on the cost
      of orbital trauma care. DESIGN: Comparative case series and database study.
      PARTICIPANTS: Four hundred ninety-nine patients who underwent orbital
      reconstruction at either a high-volume regional eye trauma center, its academic
      parent institution, or all other hospitals in Maryland between 2004 and 2009.
      METHODS: We used a publicly available database of hospital discharge data to
      identify the study population's clinical and cost characteristics. Multivariate
      models were developed to determine the impact of care setting on hospital costs
      while controlling for patient demographic and clinical variables. MAIN OUTCOME
      MEASURES: Mean hospital costs accrued during hospital admission for orbital
      reconstruction in 3 separate care settings. RESULTS: Almost half (n = 248) of all
      patients received surgical care at the regional eye trauma center and had
      significantly lower adjusted mean hospital costs ($6194; 95% confidence interval
      [CI], $5709-$6719) compared with its parent institution ($8642; 95% CI, $7850
      $9514) and all other hospitals ($12,692; 95% CI, $11,467-$14,047). A
      subpopulation analysis selecting patients with low comorbidity scores also was
      performed. The eye trauma center continued to have lower adjusted costs ($4277;
      95% CI, $4112-$4449) relative to its parent institution ($6595; 95% CI, $5838
      $7451) and other hospitals ($7150; 95% CI, $5969-$8565). CONCLUSIONS: Higher
      volume and specialization seen at a regional eye trauma center are associated
      with lower costs in the surgical management of orbital trauma.

PMID- 24120327
TI  - Development of the functional vision questionnaire for children and young people
      with visual impairment: the FVQ_CYP.
AB  - OBJECTIVE: To develop a novel age-appropriate measure of functional vision (FV)
      for self-reporting by visually impaired (VI) children and young people. DESIGN:
      Questionnaire development. PARTICIPANTS: A representative patient sample of VI
      children and young people aged 10 to 15 years, visual acuity of the logarithm of
      the minimum angle of resolution (logMAR) worse than 0.48, and a school-based
      (nonrandom) expert group sample of VI students aged 12 to 17 years. METHODS: A
      total of 32 qualitative semistructured interviews supplemented by narrative
      feedback from 15 eligible VI children and young people were used to generate
      draft instrument items. Seventeen VI students were consulted individually on item
      relevance and comprehensibility, instrument instructions, format, and
      administration methods. The resulting draft instrument was piloted with 101 VI
      children and young people comprising a nationally representative sample, drawn
      from 21 hospitals in the United Kingdom. Initial item reduction was informed by
      presence of missing data and individual item response pattern. Exploratory factor
      analysis (FA) and parallel analysis (PA), and Rasch analysis (RA) were applied to
      test the instrument's psychometric properties. MAIN OUTCOME MEASURES:
      Psychometric indices and validity assessment of the Functional Vision
      Questionnaire for Children and Young People (FVQ_CYP). RESULTS: A total of 712
      qualitative statements became a 56-item draft scale, capturing the level of
      difficulty in performing vision-dependent activities. After piloting, items were
      removed iteratively as follows: 11 for high percentage of missing data, 4 for
      skewness, and 1 for inadequate item infit and outfit values in RA, 3 having shown
      differential item functioning across age groups and 1 across gender in RA. The
      remaining 36 items showed item fit values within acceptable limits, good
      measurement precision and targeting, and ordered response categories. The reduced
      scale has a clear unidimensional structure, with all items having a high factor
      loading on the single factor in FA and PA. The summary scores correlated
      significantly with visual acuity. CONCLUSIONS: We have developed a novel,
      psychometrically robust self-report questionnaire for children and young people
      the FVQ_CYP-that captures the functional impact of visual disability from their
      perspective. The 36-item, 4-point unidimensional scale has potential as a
      complementary adjunct to objective clinical assessments in routine pediatric
      ophthalmology practice and in research.

PMID- 24120329
TI  - Cognitive profile in Wilson's disease: a case series of 31 patients.
AB  - BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive disorder of
      copper metabolism. If untreated, WD, which is initially a liver disease, can turn
      into a multi-systemic disease with neurological involvement. Very few studies
      have described cognitive impairment in WD. The aim of this study is to report the
      cognitive profile of 31 treated WD patients. METHODS: Patients were classed into
      two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients
      without neurological signs (WD-N(-)) (n=13), and WD patients with neurological
      signs (WD-N(+)) (n=18). The patients participated in a neuropsychological
      assessment evaluating memory, executive function and visuo-spatial abilities.
      RESULTS: Both groups performed well for verbal intelligence and episodic memory
      skills. However, the majority of these patients exhibited altered performance for
      at least one cognitive test, particularly in the executive domain. The WD-N(+)
      group performed less well than the WD-N(-) group on cognitive tests involving
      rapid motor function, abstract thinking, working memory and top-down inhibitory
      control. CONCLUSIONS: Cognitive impairment in treated WD patients essentially
      affects executive function involving fronto-striatal circuits. Verbal
      intelligence and episodic memory abilities seem to be remarkably preserved.
      Neuropsychological assessment is a valuable tool to evaluate the presence and the
      consequences of these cognitive impairments in WD patients with or without
      neurological signs in the course of this chronic disease.

PMID- 24120328
TI  - Prediction of age-related macular degeneration in the general population: the
      Three Continent AMD Consortium.
AB  - PURPOSE: Prediction models for age-related macular degeneration (AMD) based on
      case-control studies have a tendency to overestimate risks. The aim of this study
      is to develop a prediction model for late AMD based on data from population-based
      studies. DESIGN: Three population-based studies: the Rotterdam Study (RS), the
      Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the
      Three Continent AMD Consortium (3CC). PARTICIPANTS: People (n = 10,106) with
      gradable fundus photographs, genotype data, and follow-up data without late AMD
      at baseline. METHODS: Features of AMD were graded on fundus photographs using the
      3CC AMD severity scale. Associations with known genetic and environmental AMD
      risk factors were tested using Cox proportional hazard analysis. In the RS, the
      prediction of AMD was estimated for multivariate models by area under receiver
      operating characteristic curves (AUCs). The best model was validated in the BDES
      and BMES, and associations of variables were re-estimated in the pooled data set.
      Beta coefficients were used to construct a risk score, and risk of incident late
      AMD was calculated using Cox proportional hazard analysis. Cumulative incident
      risks were estimated using Kaplan-Meier product-limit analysis. MAIN OUTCOME
      MEASURES: Incident late AMD determined per visit during a median follow-up period
      of 11.1 years with a total of 4 to 5 visits. RESULTS: Overall, 363 participants
      developed incident late AMD, 3378 participants developed early AMD, and 6365
      participants remained free of any AMD. The highest AUC was achieved with a model
      including age, sex, 26 single nucleotide polymorphisms in AMD risk genes,
      smoking, body mass index, and baseline AMD phenotype. The AUC of this model was
      0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled
      analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.02 (95%
      confidence interval [CI], 0.01-0.04) to develop late AMD, and individuals with
      high-risk scores had an HR of 22.0 (95% CI, 15.2-31.8). Cumulative risk of
      incident late AMD ranged from virtually 0 to more than 65% for those with the
      highest risk scores. CONCLUSIONS: Our prediction model is robust and
      distinguishes well between those who will develop late AMD and those who will
      not. Estimated risks were lower in these population-based studies than in
      previous case-control studies.

PMID- 24120330
TI  - Prescription drug coupons: evolution and need for regulation in direct-to
      consumer advertising.
AB  - Pharmaceutical marketing in the United States had undergone a shift from largely
      exclusively targeting physicians to considerable efforts in targeting patients
      through various forms of direct-to-consumer advertising ("DTCA"). This includes
      the use of DTCA in prescription drug coupons ("PDCs"), a new form of DTCA that
      offers discounts and rebates directly to consumers to lower costs of drug
      purchasing. Our examination of PDCs reveals that the use and types of PDC
      programs is expanding and includes promotion of the vast majority of top grossing
      pharmaceuticals. However, controversy regarding this emerging form of DTCA has
      given rise to health policy concerns about their overall impact on prescription
      drug expenditures for consumers, payers, and the health care system, and whether
      they lead to optimal long-term utilization of pharmaceuticals. In response to
      these concerns and the growing popularity of PDCs, what we propose here are
      clearer regulation and regulatory guidance for PDC DTCA use. This would include
      review for appropriate disclosure of marketing claims, increased transparency in
      PDC use for pharmaceutical pricing, and leveraging potential positive benefits of
      PDC use for vulnerable or underserved patient populations. 

PMID- 24120331
TI  - A cryptic polyene biosynthetic gene cluster in Streptomyces calvus is expressed
      upon complementation with a functional bldA gene.
AB  - Streptomyces calvus is best known as the producer of the fluorinated natural
      product nucleocidin. This strain of Streptomycetes is also unusual for displaying
      a "bald" phenotype that is deficient in the formation of aerial mycelium and
      spores. Genome sequencing of this organism revealed a point mutation in the bldA
      gene that is predicted to encode a misfolded Leu-tRNA(UUA) molecule.
      Complementation of S. calvus with a correct copy of bldA restored sporulation and
      additionally promoted production of a polyeneoic acid amide, 4-Z-annimycin, and a
      minor amount of the isomer, 4-E-annimycin. Bioassays reveal that these compounds
      inhibit morphological differentiation in other Actinobacteria. The annimycin gene
      cluster encoding a type 1 polyketide synthase was identified and verified through
      disruption studies. This study underscores the importance of the bldA gene in
      regulating the expression of cryptic biosynthetic genes. 

PMID- 24120333
TI  - Characterization of a proteolytically stable multifunctional host defense
      peptidomimetic.
AB  - The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated.
      The compound exhibited an antimicrobial activity profile against a range of Gram
      negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized
      the inner membrane at its minimal inhibitory concentration (MIC). Moreover, it
      was demonstrated that HDM-4 was distributed widely in the bacterial cell at
      lethal concentrations, and that it could bind to DNA. It was confirmed that the
      multimodal action of HDM-4 resulted in it being less likely to lead to resistance
      development as compared to single-target antibiotics. HDM-4 exhibited
      multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4
      modulated the immune response by inducing the release of the chemoattractants
      interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from
      human peripheral blood mononuclear cells. In addition, the compound suppressed
      lipopolysaccharide-mediated inflammation by reducing the release of the pro
      inflammatory cytokines IL-6 and tumor necrosis factor-alpha.

PMID- 24120332
TI  - Peptide-based inhibitors of Plk1 polo-box domain containing mono-anionic
      phosphothreonine esters and their pivaloyloxymethyl prodrugs.
AB  - Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine
      (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper
      function of Plk1. Although high-affinity synthetic pThr-containing peptides may
      be used to disrupt PBD function, the efficacy of such peptides in whole cell
      assays has been poor. This potentially reflects limited cell membrane
      permeability arising in part from the di-anionic nature of the phosphoryl group.
      We report five-mer peptides containing mono-anionic pThr phosphoryl esters that
      exhibit single-digit nanomolar PBD binding affinities in extracellular assays and
      improved antimitotic efficacies in whole cell assays. The cellular efficacies of
      these peptides have been further enhanced by the application of bio-reversible
      pivaloyloxymethyl (POM) phosphoryl protection to a pThr-containing polypeptide.
      Our findings may redefine structural parameters for the development of PBD
      binding peptides and peptide mimetics. 

PMID- 24120334
TI  - The essence of management of Barrett's esophagus.

PMID- 24120335
TI  - EUS-guided angiotherapy for gastric varices: coil, glue, and sticky issues.

PMID- 24120336
TI  - EUS-guided biliary drainage: taxing and not ready.

PMID- 24120337
TI  - Gastric peroral endoscopic myotomy for refractory gastroparesis: first human
      endoscopic pyloromyotomy (with video).

PMID- 24120338
TI  - Endoscopic treatment of acute variceal hemorrhage by using hemostatic powder TC
      325: a prospective pilot study.
AB  - BACKGROUND: Current standard of care of acute variceal bleeding (AVB) combines
      hemodynamic stabilization, antibiotic prophylaxis, pharmacological agents, and
      endoscopic treatment. The latter may be challenging in an emergency setting with
      active bleeding that interferes with visualization. OBJECTIVE: To assess the
      effectiveness of a pre-established delivery protocol of a hemostatic powder to
      control AVB originating from the esophagus or the gastroesophageal junction.
      DESIGN: Prospective, 2-center study. SETTING: Two tertiary-care referral
      university hospitals. PATIENTS: Nine patients who received endoscopic hemostatic
      powder for actively bleeding varices. INTERVENTIONS: Endoscopic hemostasis. MAIN
      OUTCOME MEASUREMENT: Primary hemostasis and rebleeding rates. RESULTS: Nine
      consecutive patients with confirmed AVB underwent treatment within 12 hours of
      hospital admission. Bleeding stopped during the endoscopy performed with
      application of 21 g of hemostatic powder from the cardia up to 15 cm above the
      gastroesophageal junction. No rebleeding was observed in any of the patients
      within 24 hours. No mortality was observed at 15-day follow-up. LIMITATIONS:
      Small sample size. CONCLUSION: Hemostatic powder has the potential to temporarily
      stop AVB. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01783899.)

PMID- 24120339
TI  - Carbon dioxide insufflation for colonoscopy.

PMID- 24120340
TI  - Response.

PMID- 24120341
TI  - Diagnostic yield of small-bowel capsule endoscopy in patients with iron
      deficiency anemia: does it affect management?

PMID- 24120342
TI  - Response.

PMID- 24120343
TI  - Acknowledging the first author and corresponding author of published work.

PMID- 24120344
TI  - Rapid intraluminal growth of a colorectal cancer observed by endoscopy.

PMID- 24120345
TI  - The Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth):
      design, objectives, and procedures.
AB  - PURPOSE: This article describes the design and methodology of the Study of Latino
      Youth (SOL Youth) study, a multicenter study of Hispanic/Latino children living
      in the United States. METHODS: Participants are children aged 8-16 years whose
      parents/legal guardians participated in the Hispanic Community Health Study/Study
      of Latinos, a large community-based cohort study of Hispanic/Latino adults living
      in the United States. RESULTS: Between 2012 and 2014, 1600 children recruited
      from four field centers (Bronx, Chicago, Miami, and San Diego) will undergo a 3.5
      hour examination to collect biospecimens, obtain anthropometric measures, blood
      pressure, fitness level, dietary intake, and physical activity. Psychosocial and
      environmental characteristics are assessed by questionnaire. Primary study aims
      are to examine associations of youth's lifestyle behaviors and cardiometabolic
      risk factors with (1) youth's acculturation and parent-child differences in
      acculturation; (2) parenting strategies, family behaviors, and parental health
      behaviors; and (3) youth's psychosocial functioning. CONCLUSIONS: SOL Youth will
      determine the prevalence and distribution of obesity-promoting lifestyle
      behaviors, cardiometabolic risk profiles, and novel biomarkers associated with
      obesity and insulin resistance. This article describes the study methodology and
      considers advantages and limitations of embedding a cohort of children within a
      well-characterized cohort of adults.

PMID- 24120346
TI  - Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5,
      6, and 7 induce TGFbeta-1 signaling in ovarian cancer cells.
AB  - Kallikrein-related peptidases, in particular KLK4, 5, 6 and 7 (4-7), often have
      elevated expression levels in ovarian cancer. In OV-MZ-6 ovarian cancer cells,
      combined expression of KLK4-7 reduces cell adhesion and increases cell invasion
      and resistance to paclitaxel. The present work investigates how KLK4-7 shape the
      secreted proteome ("secretome") and proteolytic profile ("degradome") of ovarian
      cancer cells. The secretome comparison consistently identified >900 proteins in
      three replicate analyses. Expression of KLK4-7 predominantly affected the
      abundance of proteins involved in cell-cell communication. Among others, this
      includes increased levels of transforming growth factor beta-1 (TGFbeta-1). KLK4
      7 co-transfected OV-MZ-6 cells share prominent features of elevated TGFbeta-1
      signaling, including increased abundance of neural cell adhesion molecule L1
      (L1CAM). Augmented levels of TGFbeta-1 and L1CAM upon expression of KLK4-7 were
      corroborated in vivo by an ovarian cancer xenograft model. The degradomic
      analysis showed that KLK4-7 expression mostly affected cleavage sites C-terminal
      to arginine, corresponding to the preference of kallikreins 4, 5 and 6. Putative
      kallikrein substrates include chemokines, such as growth differentiation factor
      15 (GDF 15) and macrophage migration inhibitory factor (MIF). Proteolytic
      maturation of TGFbeta-1 was also elevated. KLK4-7 have a pronounced, yet non
      degrading impact on the secreted proteome, with a strong association between
      these proteases and TGFbeta-1 signaling in tumor biology.

PMID- 24120348
TI  - Functional characterization and transcriptional analysis of galE gene encoding a
      UDP-galactose 4-epimerase in Xanthomonas campestris pv. campestris.
AB  - The Gram-negative plant pathogen Xanthomonas campestris pv. campestris (Xcc) is
      the causative agent of black rot in crucifers, a disease that causes tremendous
      agricultural loss. In this study, the Xcc galE gene was characterized. Sequence
      and mutational analysis demonstrated that the Xcc galE encodes a UDP-galactose 4
      epimerase (EC 5.1.3.2), which catalyzes the interconversion of UDP-galactose and
      UDP-glucose. Alanine substitution of the putative catalytic residues (Ser124,
      Tyr147, and Lys151) of GalE caused loss of epimerase activity. Further study
      showed that the Xcc galE mutant had reduced biofilm formation ability.
      Furthermore, reporter assays revealed that galE transcription exhibits a distinct
      expression profile under different culture conditions, is subject to catabolite
      repression, and is positively regulated by Clp and RpfF. In addition, the galE
      transcription initiation site was mapped. This is the first time that UDP
      galactose 4-epimerase has been characterized in the crucifer pathogen Xcc. 

PMID- 24120347
TI  - The Drosophila putative histone acetyltransferase Enok maintains female germline
      stem cells through regulating Bruno and the niche.
AB  - Maintenance of adult stem cells is largely dependent on the balance between their
      self-renewal and differentiation. The Drosophila ovarian germline stem cells
      (GSCs) provide a powerful in vivo system for studying stem cell fate regulation.
      It has been shown that maintaining the GSC population involves both genetic and
      epigenetic mechanisms. Although the role of epigenetic regulation in this process
      is evident, the underlying mechanisms remain to be further explored. In this
      study, we find that Enoki mushroom (Enok), a Drosophila putative MYST family
      histone acetyltransferase controls GSC maintenance in the ovary at multiple
      levels. Removal or knockdown of Enok in the germline causes a GSC maintenance
      defect. Further studies show that the cell-autonomous role of Enok in maintaining
      GSCs is not dependent on the BMP/Bam pathway. Interestingly, molecular studies
      reveal an ectopic expression of Bruno, an RNA binding protein, in the GSCs and
      their differentiating daughter cells elicited by the germline Enok deficiency.
      Misexpression of Bruno in GSCs and their immediate descendants results in a GSC
      loss that can be exacerbated by incorporating one copy of enok mutant allele.
      These data suggest a role for Bruno in Enok-controlled GSC maintenance. In
      addition, we observe that Enok is required for maintaining GSCs non-autonomously.
      Compromised expression of enok in the niche cells impairs the niche maintenance
      and BMP signal output, thereby causing defective GSC maintenance. This is the
      first demonstration that the niche size control requires an epigenetic mechanism.
      Taken together, studies in this paper provide new insights into the GSC fate
      regulation.

PMID- 24120349
TI  - Herniation of the lung: a case report.
AB  - BACKGROUND: Chest pain accounts for a significant number of visits to the
      Emergency Department. Lung herniation is an uncommon cause of chest pain, but one
      that is easily treated. Patients may complain of pain or present with ecchymosis
      or a visible bulge in the chest wall. Most lung herniations are located
      anteriorly or at the thoracic inlet, due to the lack of musculature in these
      areas. We present a unique case of a right lateral lung herniation and subsequent
      development of a spontaneous right-sided transdiaphragmatic hernia. OBJECTIVES:
      To discuss the presentation of a patient found to have a spontaneous lung and
      bowel herniation, and to review the literature regarding these entities. CASE
      REPORT: A 61-year old gentleman with a history of chronic obstructive pulmonary
      disease and previous long-standing smoking history presented with complaints of
      right-sided chest pain and cough. He was found to have a spontaneous right
      lateral lung herniation. This was managed expectantly, but the patient
      subsequently developed spontaneous right-sided diaphragmatic rupture and
      herniation of bowel contents through the chest wall. CONCLUSION: To our
      knowledge, this is the first reported case of a patient presenting with
      spontaneous right-sided lateral lung herniation and spontaneous right-sided
      transdiaphragmatic hernia. This case is unusual given the location of the
      hernias, and is unique in the spontaneous development of the hernias without any
      inciting history of trauma.

PMID- 24120350
TI  - Ultrastructure of Clostridium difficile colonies.
AB  - The ultrastructural colony architecture of six Clostridium difficile strains
      belonging to four different ribotypes (001, 027, 078/126 and 036) was studied by
      scanning electron microscopy (SEM). In 2-day-old colonies several microareas
      differing in cell length and organization could be differentiated. Some cells at
      colony edges were extremely long and exhibited invasiveness into the agar. The
      ultrastructure of 5-day-old colonies is more homogenous and characterized by
      presence of sporulating cells, spores and extracellular matrix. 

PMID- 24120351
TI  - Advances in imaging probes and optical microendoscopic imaging techniques for
      early in vivo cancer assessment.
AB  - A new chapter in the history of medical diagnosis happened when the first X-ray
      technology was invented in the late 1800s. Since then, many non-invasive and
      minimally invasive imaging techniques have been invented for clinical diagnosis
      to research in cellular biology, drug discovery, and disease monitoring. These
      imaging modalities have leveraged the benefits of significant advances in
      computer, electronics, and information technology and, more recently, targeted
      molecular imaging. The development of targeted contrast agents such as
      fluorescent and nanoparticle probes coupled with optical imaging techniques has
      made it possible to selectively view specific biological events and processes in
      both in vivo and ex vivo systems with great sensitivity and selectivity. Thus,
      the combination of targeted molecular imaging probes and optical imaging
      techniques have become a mainstay in modern medicinal and biological research.
      Many promising results have demonstrated great potentials to translate to
      clinical applications. In this review, we describe a discussion of employing
      imaging probes and optical microendoscopic imaging techniques for cancer
      diagnosis. 

PMID- 24120352
TI  - Promoting clinical and laboratory interaction by harmonization.
AB  - The lack of interchangeable results in current practice among clinical
      laboratories has underpinned greater attention to standardization and
      harmonization projects. Although the focus was mainly on the standardization and
      harmonization of measurement procedures and their results, the scope of
      harmonization goes beyond method and analytical results: it includes all other
      aspects of laboratory testing, including terminology and units, report formats,
      reference limits and decision thresholds, as well as test profiles and criteria
      for the interpretation of results. In particular, as evidence collected in last
      decades demonstrates that pre-pre- and post-post-analytical steps are more
      vulnerable to errors, harmonization initiatives should be performed to improve
      procedures and processes at the laboratory-clinical interface. Managing upstream
      demand, down-stream interpretation of laboratory results, and subsequent
      appropriate action through close relationships between laboratorians and
      clinicians remains a crucial issue of the laboratory testing process. Therefore,
      initiatives to improve test demand management from one hand and to harmonize
      procedures to improve physicians' acknowledgment of laboratory data and their
      interpretation from the other hand are needed in order to assure quality and
      safety in the total testing process.

PMID- 24120353
TI  - Measurement of ganciclovir concentration in human plasma by ultra-performance
      liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Ganciclovir/valganciclovir plays an important role in the treatment
      and prevention of cytomegalovirus disease after organ transplantation. MATERIAL
      AND METHODS: We developed and validated a simple chromatographic method by ultra
      performance liquid chromatography tandem mass spectrometry to measure plasma
      concentration of ganciclovir in human plasma. Chromatographic separation was
      achieved using an Acquity((r)) UPLC((r)) BEHTM (2.1*50mm id, 1.7MUm) reverse
      phase C18 column, with a water/methanol linear gradient containing ammonium
      acetate/formic acid at a 0.4mL/min flow rate. Ganciclovir and its internal
      standard (acyclovir) were detected by electrospray ionization mass spectrometry
      in positive ion multiple reaction monitoring mode. RESULTS: The limit of
      detection and quantification were 0.03 and 0.06mg/L, respectively, and linearity
      was observed between 0.06 and 30.0mg/L. Intra-day and day-to-day coefficients of
      variation and relative biases ranged from 3.6 to 5.4%, 4.2 to 6.2%, -2.6 to -1.1%
      and -4.0 to -2.8%, respectively. Recovery values were greater than 81.9%.
      Evaluation of the matrix effect showed ion suppression for ganciclovir and
      acyclovir. No carry-over was observed. CONCLUSIONS: The validated method is
      useful for both therapeutic drug monitoring and pharmacokinetic studies. It could
      be applied to the daily clinical laboratory practice to measure the concentration
      of ganciclovir in human plasma.

PMID- 24120354
TI  - Prolonged and recurrent fevers in children.
AB  - Some children referred for prolonged fever are actually not having elevated
      temperatures; the approach here requires dissection of the history and correction
      of health misperceptions. Others have well-documented fevers associated with
      clinical, laboratory, or epidemiologic findings that should point to a specific
      diagnosis. "Fever-of-Unknown-Origin" (FUO) is the clinical scenario of daily
      fever for >= 14 days that defies explanation after a careful history, physical
      examination, and basic laboratory tests. The diagnostic approach requires a
      meticulous fever diary, serial clinical and laboratory evaluations, vigilance for
      the appearance of new signs and symptoms, and targeted investigations; the pace
      of the work-up is determined by the severity of the illness. Approximately half
      of children with FUO will have a self-limited illness and will never have a
      specific diagnosis made; the other half will ultimately be found to have, in
      order, infectious, inflammatory, or neoplastic conditions. Irregular,
      intermittent, recurrent fevers in the well-appearing child are likely to be
      sequential viral illnesses. Monogenic autoinflammatory diseases should be
      considered in those who do not fit the picture of recurrent infections and who do
      not have hallmarks of immune deficiency. Stereotypical febrile illnesses that
      recur with clockwork periodicity should raise the possibilities of cyclic
      neutropenia, if the cycle is approximately 21 days, or periodic fever, aphthous
      stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic
      fever in childhood.

PMID- 24120355
TI  - Rapid acquisition of the transcranial magnetic stimulation stimulus response
      curve.
AB  - BACKGROUND: Transcranial magnetic stimulation is frequently used to construct
      stimulus response (SR) curves in studies of motor learning and rehabilitation. A
      drawback of the established method is the time required for data acquisition,
      which is frequently greater than a participant's ability to maintain attention.
      The technique is therefore difficult to use in the clinical setting. OBJECTIVE:
      To reduce the time of curve acquisition by determining the minimum acquisition
      time and number of stimuli required to acquire an SR curve. METHODS: SR curves
      were acquired from first dorsal interosseous (FDI) and abductor digiti minimi
      (ADM) at 6 interstimulus intervals (ISI) between 1.4 and 4 s in 12 participants.
      To determine if low-frequency rTMS might affect the SR curve, MEP amplitudes were
      monitored before and after 3 min of 1 Hz rTMS delivered at 120% of resting motor
      threshold in 12 participants. Finally, SR curves were acquired from FDI, ADM and
      Biceps Brachii (BB) in 12 participants, and the minimum number of stimuli was
      calculated using a sequential MEP elimination process. RESULTS: There were no
      significant differences between curves acquired with 1.4 s ISI and any other ISI.
      Low frequency rTMS did not significantly depress MEP amplitude (P = 0.87). On
      average, 61 +/- 18 (FDI), 60 +/- 16 (ADM) and 59 +/- 16 (BB) MEPs were needed to
      construct a representative SR curve. CONCLUSIONS: This study demonstrates that
      reliable SR curves may be acquired in less than 2 min. At this rate, SR curves
      become a clinically feasible method for assessing corticospinal excitability in
      research and rehabilitation settings.

PMID- 24120356
TI  - Sex dependent risk management in face of perceived danger of socially foraging
      Bee-eaters (Merops apiaster) during migration.
AB  - The proximal reasons and ultimal consequences of decisions made during foraging
      by breeding individuals are widely studied in numerous avian systems. However,
      the effects of these decisions are more pronounced in migratory birds because
      they spend more time and energy foraging than on the actual journey itself. The
      peak flowering and pollination period of crops in southern Israel, when large
      numbers of hives are transported to the region, coincide with the peak migration
      of Bee-eaters. We hypothesized that Bee-eaters cue on conspecifics while foraging
      at a stopover site, react to perceived danger at a given foraging patch, and that
      the degree of risk taken by an individual was a function of body condition and
      sex. Bee-eaters were caught on 44 different mornings in spring 2004, 2005, and
      2009. A sex-dependent trapping was noted and significantly more females were
      caught in the first bout. The sex ratio remained significantly male biased in
      bouts 3-8. Birds caught in the first bout were heavier in comparison to those
      caught in the second bout, and there was a significant interaction between sex
      and bouts. From the second bout onwards both sexes showed a significant increase
      in body mass, by 1.05g/bout on average (+/-0.6 SD), however wing lengths remained
      similar for both sexes. We conclude that migrant Bee-eaters cue on conspecifics
      to evaluate predation risks when socially foraging at a localized food patch and
      males, who we assume to be time-minimizers, are more likely to forage at a novel
      site and once danger of foraging is perceived only high energy demand individuals
      will attempt to hunt. 

PMID- 24120357
TI  - Is there a skeletal muscle mass threshold associated with the deterioration of
      insulin sensitivity in sedentary lean to obese postmenopausal women?
AB  - AIM: The purpose of this study was to determine an optimal cut-off point of
      skeletal muscle mass, using appendicular lean body mass (LBM) index, that
      identifies at risk individuals with deteriorated insulin sensitivity, using an
      established quantitative insulin sensitivity index (QUICKI) cut-off. METHODS: We
      performed a cross-sectional analysis in 231 lean and obese (BMI: 18.7-51.0
      kg/m(2)) menopausal women. Fasting plasma glucose and insulin were obtained to
      calculate QUICKI as an index of insulin sensitivity. Skeletal muscle mass was
      measured as appendicular LBM by DXA and expressed as appendicular LBM index
      [appendicular LBM (kg)/height (m(2))]. Cut-offs were determined using receiver
      operating characteristic (ROC) curve analyses. RESULTS: The best cut-off value
      for skeletal muscle mass index to identify menopausal women with reduced insulin
      sensitivity was 7.025 kg/m(2) which had a sensitivity of 69.5% and specificity of
      58.2%. CONCLUSION: Our results suggest that sedentary postmenopausal women with
      an appendicular skeletal muscle mass index above 7.025 kg/m(2) may be at greater
      risk of insulin resistance. Prospective studies are needed to validate our
      result.

PMID- 24120358
TI  - The impact of microRNAs on the regulation of tissue factor biology.
AB  - Tissue factor (TF) and its isoforms play an important role in a variety of
      physiologic and pathophysiologic functions, such as initiation of blood
      coagulation, vessel wall hemostasis, angiogenesis, and tumorigenesis.
      Micro(mi)RNAs are crucial for post-transcriptional control of protein generation
      by regulating the expression of one-third of all human genes. In recent years,
      miRNAs were shown to modulate the expression and biologic function of TF in
      different physiologic- and pathophysiologic-relevant settings, such as in
      autoimmune diseases and in different types of cancer. In the present review, we
      will summarize and discuss the latest findings regarding the impact of miRNAs on
      the generation of TF and its isoforms as well as on regulation of TF biology
      under normal and pathophysiologic conditions. 

PMID- 24120359
TI  - The crystal structure of lipopolysaccharide binding protein reveals the location
      of a frequent mutation that impairs innate immunity.
AB  - Lipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that
      initiates an immune response after recognition of bacterial LPS. Here, we report
      the crystal structure of murine LBP at 2.9 A resolution. Several structural
      differences were observed between LBP and the related bactericidal/permeability
      increasing protein (BPI), and the LBP C-terminal domain contained a negatively
      charged groove and a hydrophobic "phenylalanine core." A frequent human LBP SNP
      (allelic frequency 0.08) affected this region, potentially generating a
      proteinase cleavage site. The mutant protein had a reduced binding capacity for
      LPS and lipopeptides. SNP carriers displayed a reduced cytokine response after in
      vivo LPS exposure and lower cytokine concentrations in pneumonia. In a
      retrospective trial, the LBP SNP was associated with increased mortality rates
      during sepsis and pneumonia. Thus, the structural integrity of LBP may be crucial
      for fighting infections efficiently, and future patient stratification might help
      to develop better therapeutic strategies. 

PMID- 24120360
TI  - Epigenetic modifications induced by Blimp-1 Regulate CD8+ T cell memory
      progression during acute virus infection.
AB  - The transcription factor Blimp-1 regulates the overall accumulation of virus
      specific CD8+ T cells during acute viral infections. We found that increased
      proliferation and survival of Blimp-1-deficient CD8+ T cells resulted from
      sustained expression of CD25 and CD27 and persistent cytokine responsiveness.
      Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8+ T cell response.
      Genome-wide chromatin immunoprecipitation (ChIP) sequencing analysis identified
      Il2ra and Cd27 as direct targets of Blimp-1. At the peak of the antiviral
      response, but not earlier, Blimp-1 recruited the histone-modifying enzymes G9a
      and HDAC2 to the Il2ra and Cd27 loci, thereby repressing expression of these
      genes. In the absence of Blimp-1, Il2ra and Cd27 exhibited enhanced histone H3
      acetylation and reduced histone H3K9 trimethylation. These data elucidate a
      central mechanism by which Blimp-1 acts as an epigenetic regulator and enhances
      the numbers of short-lived effector cells while suppressing the development of
      memory-precursor CD8+ T cells.

PMID- 24120361
TI  - An ACT1 mutation selectively abolishes interleukin-17 responses in humans with
      chronic mucocutaneous candidiasis.
AB  - Patients with inborn errors of interleukin-17F (IL-17F) or IL-17RA display
      chronic mucocutaneous candidiasis (CMC). We report a biallelic missense mutation
      (T536I) in the adaptor molecule ACT1 in two siblings with CMC. The mutation,
      located in the SEFIR domain, abolished the homotypic interaction of ACT1 with IL
      17 receptors, with no effect on homodimerization. The patients' fibroblasts
      failed to respond to IL-17A and IL-17F, and their T cells to IL-17E. By contrast,
      healthy individuals homozygous for the common variant D10N, located in the ACT1
      tumor necrosis factor receptor-associated factor-interacting domain and
      previously associated with psoriasis, had impaired, but not abolished, responses
      to IL-17 cytokines. SEFIR-independent interactions of ACT1 with other proteins,
      such as CD40, heat shock protein 70 (HSP70) and HSP90, were not affected by the
      T536I mutation. Overall, human IL-17A and IL-17F depend on ACT1 to mediate
      protective mucocutaneous immunity. Moreover, other ACT1-dependent IL-17 cytokines
      seem to be largely redundant in host defense. 

PMID- 24120363
TI  - Antibiotics from neglected bacterial sources.
AB  - The current crop of antibiotics in clinical use are either natural products or
      their derivatives. However, the rise of a multitude of different antibiotic
      resistant human pathogens has meant that new antibiotics are urgently needed.
      Unfortunately, the search for new antibiotics from traditional bacterial sources
      often results in a high rediscovery rate of known compounds and a low chance of
      identifying truly novel chemical entities. To overcome this, previously
      unexplored (or under investigated) bacterial sources are being tapped for their
      potential to produce novel compounds with new activities. Here, we review a
      number of antibiotic compounds identified from bacteria of the genera
      Burkholderia, Clostridium, Lysobacter, Pantoea and Xenorhabdus and describe the
      potential of organisms and their associated metabolites in future drug discovery
      efforts. 

PMID- 24120362
TI  - A single peptide-major histocompatibility complex ligand triggers digital
      cytokine secretion in CD4(+) T cells.
AB  - We have developed a single-molecule imaging technique that uses quantum-dot
      labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4(+) T
      cell functional sensitivity. We found that naive T cells, T cell blasts, and
      memory T cells could all be triggered by a single pMHC to secrete tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-2 (IL-2) cytokines with a rate of
      ~1,000, ~10,000, and ~10,000 molecules/min, respectively, and that additional
      pMHCs did not augment secretion, indicating a digital response pattern. We also
      found that a single pMHC localized to the immunological synapse induced the slow
      formation of a long-lasting T cell receptor (TCR) cluster, consistent with a
      serial engagement mechanism. These data show that scaling up CD4(+) T cell
      cytokine responses involves increasingly efficient T cell recruitment rather than
      greater cytokine production per cell. 

PMID- 24120364
TI  - Molecular evolution of the nicotinic acid requirement within the Shigella/EIEC
      pathotype.
AB  - Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor in several anabolic
      and catabolic reactions. NAD derives from quinolinic acid (QUIN) which in
      Escherichia coli is obtained through a pyridine salvage pathway or a de novo
      synthesis pathway. In the latter case, two enzymes, L-aspartate oxidase (NadB)
      and quinolinate synthase (NadA), are required for the synthesis of QUIN. In
      contrast to its E. coli ancestor, Shigella spp., the causative agent of bacillary
      dissentery, lacks the de novo pathway and strictly requires nicotinic acid for
      growth (Nic- phenotype). This phenotype depends on the silencing of the nadB and
      nadA genes and its pathoadaptive nature is suggested by the observation that QUIN
      attenuates the Shigella invasive process. Shigella shares the pathogenicity
      mechanism with enteronvasive E. coli (EIEC), a group of pathogenic E. coli. On
      the basis of this similarity EIEC and Shigella have been grouped into a single E.
      coli pathotype. However EIEC strains do not constitute a homogeneous group and do
      not possess the complete set of characters that define Shigella strains. In this
      work we have analysed thirteen EIEC strains belonging to different serotypes and
      originating from different geographic areas. We show that, in contrast to
      Shigella, only some EIEC strains require nicotinic acid for growth in minimal
      medium. Moreover, by studying the emergence of the Nic- phenotype in all
      serotypes of S. flexneri, as well as in S. sonnei and S. dysenteriae, we describe
      which molecular rearrangements occurred and which mutations are responsible for
      the inactivation of the nadA and nadB genes. Our data confirm that the genome of
      Shigella is extremely dynamic and support the hypothesis that EIEC might reflect
      an earlier stage of the pathoadaptation process undergone by Shigella.

PMID- 24120365
TI  - Early Staphylococcus aureus-induced changes in endothelial barrier function are
      strain-specific and unrelated to bacterial translocation.
AB  - The vascular endothelium provides the critical barrier during hematogenous
      spreading of bacteria, a phenomenon that might contribute to severe diseases in
      humans including endocarditis and sepsis as known from infections by
      Staphylococcus aureus. Here we aimed to uncover early responses of the
      endothelium to S. aureus infection with respect to (a) inflammatory reactions
      such as paracellular endothelial barrier function and expression of cell adhesion
      molecule-1 (ICAM-1) and (b) translocation through the endothelium. After
      infection of the cultured endothelium with 22 different clinical isolates of S.
      aureus and two well-characterized lab strains a diverse and strain-specific
      change in para- and transcellular endothelial barrier function was observed.
      Bayesian data analysis revealed positive correlation of paracellular barrier
      function decrease followed by expression of ICAM-1 while these parameters
      negatively correlated with transcellular bacterial translocation. Translocating
      bacteria largely blocked TNFalpha-induced ICAM-1 expression indicating an active
      anti-inflammatory effect mediated by those strains probably due to
      intracellularly released virulence factors. Furthermore, the underlying
      background of barrier function decrease was investigated in more detail using two
      well-characterized lab strains, ls 8325-4 and ls 6850 and respective mutants.
      Barrier function decrease was found to be independent of early cell death and
      early release of virulence factors into the medium, but require internalization
      of live bacteria. The data show for the first time that endothelial cells respond
      diversely to infection with different strains of S. aureus and that translocating
      strains downregulate inflammatory response of the endothelium. Furthermore, data
      indicate that S. aureus-mediated activation of the endothelium reduces bacterial
      translocation. 

PMID- 24120366
TI  - Generation and characterization of a GCV resistant HCMV UL97-mutation and a drug
      sensitive UL54-mutation.
AB  - In transplant recipients, drug-resistant human cytomegalovirus (HCMV) infections
      remain a serious problem. Drug-resistance against ganciclovir (GCV), cidofovir
      (CDV) and foscarnet (PFA) is caused by mutations either in the phosphotransferase
      gene (UL97) or in the viral polymerase (UL54). For characterization of newly
      emerging mutations marker transfer analysis is required. Two new HCMV-mutations,
      the UL54-mutation L516M and the UL97-mutation A613V, were characterized by this
      method. 

PMID- 24120367
TI  - The role of opioid receptor agonists in ischemic preconditioning.
AB  - Opioids and their receptor agonists have been widely used because of their
      beneficial effects on pain management and control. Over the past decade, there
      has been an increasing interest on the experimental use of opioid agonists in the
      laboratory setting of ischemia and reperfusion; existing data suggest that there
      is a potential association between opioid agonism and the reduction of infarct
      size in several animal models of regional ischemia similar to that following
      ischemic preconditioning. Most of these studies seem to attribute these
      beneficial and cardioprotective effects to the stimulation of a specific opioid
      receptor type, the delta (delta) opioid receptor. This review focuses on the role
      of the delta opioid receptor agonism in several models of ischemia and
      reperfusion, as well as on hemorrhagic shock models, on the potential mechanisms
      of action following delta opioid receptor activation and on the time window for
      opioid administration in various animal studies. 

PMID- 24120368
TI  - Repeated exposure to stress stimuli during ethanol consumption prolongs
      withdrawal-induced emotional abnormality in mice.
AB  - The present study was designed to ascertain the influence of repeated exposure to
      stress on the development of ethanol dependence in mice. Mice were chronically
      treated with 3% ethanol for 7 days, with or without exposure to restraint stress
      for 1h/day. A significant loss of body weight was observed in the ethanol plus
      stress group compared with the other groups. In the ethanol plus stress group,
      mice exhibited persistent piloerection, which is considered to be a withdrawal
      sign that reflects emotion, after the discontinuation of ethanol treatment. The
      ethanol plus stress group also showed a marked increase in the intake of liquid
      diet, which is considered to be trying to avoid an unpleasant ethanol-withdrawal
      symptom, during ethanol withdrawal. In the hole-board test, a significant
      decrease in head-dipping behavior was observed in both the ethanol alone and
      ethanol plus stress groups at 6h after the discontinuation of ethanol treatment.
      This abnormal emotion was recovered in the ethanol alone group, but not in the
      ethanol plus stress group, at 48 h after the discontinuation of ethanol
      treatment. These results suggest that repeated exposure to stress may affect the
      development of ethanol dependence and prolong the expression of withdrawal
      induced emotional abnormality.

PMID- 24120369
TI  - Analgesic effect of sinomenine in rodents after inflammation and nerve injury.
AB  - Sinomenine is an alkaloid originally isolated from the root of the plant
      Sinomenium acutum. It is used in traditional medicine in China to treat rheumatic
      arthritis. In the present study, we evaluated the potential antinociceptive
      effects of sinomenine in rodents with nociceptive, inflammatory and neuropathic
      pain. In normal rats and mice, systemic sinomenine produced moderate
      antinociceptive effect in the hot plate and tail flick tests. Sinomenine also
      exerted analgesic effects on mechanical and heat hypersensitivity in mice after
      carrageenan induced inflammation. Finally, sinomenine effectively alleviated
      mechanical and cold allodynia in rats and mice after injury to peripheral nerve
      or spinal cord. The analgesic effect of sinomenine is not associated with side
      effects and is not reversed by the opioid receptor antagonist naloxone. Our
      results showed that sinomenine has a wide spectrum analgesic effect in rodent
      models of nociceptive, inflammatory and neuropathic pain. 

PMID- 24120370
TI  - Inhibition of fatty acid amide hydrolase and cyclooxygenase by the N-(3
      methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen.
AB  - Inhibitors of the metabolism of the endogenous cannabinoid ligand anandamide by
      fatty acid amide hydrolase (FAAH) reduce the gastric damage produced by non
      steroidal anti-inflammatory agents and synergise with them in experimental pain
      models. This motivates the design of compounds with joint FAAH/cyclooxygenase
      (COX) inhibitory activity. Here we present data on the N-(3-methylpyridin-2
      yl)amide derivatives of flurbiprofen and naproxen (Flu-AM1 and Nap-AM1,
      respectively) with respect to their properties towards these two enzymes. Flu-AM1
      and Nap-AM1 inhibited FAAH-catalysed hydrolysis of [(3)H]anandamide by rat brain
      homogenates with IC50 values of 0.44 and 0.74 uM. The corresponding values for
      flurbiprofen and naproxen were 29 and >100 uM, respectively. The inhibition by
      Flu-AM1 was reversible, mixed-type, with K(i)slope and K(i)intercept values of
      0.21 and 1.4 uM, respectively. Flurbiprofen and Flu-AM1 both inhibited COX in the
      same manner with the order of potencies COX-2 vs. 2-arachidonoylglycerol>COX-1
      vs. arachidonic acid>COX-2 vs. arachidonic acid with flurbiprofen being
      approximately 2-3 fold more potent than Flu-AM1 in the assays. Nap-AM1 was a less
      potent inhibitor of COX. Flu-AM1 at low micromolar concentrations inhibited the
      FAAH-driven uptake of [(3)H]anandamide into RBL2H3 basophilic leukaemia cells in
      vitro, but did not penetrate the brain in vivo sufficiently to block the binding
      of [(18)F]DOPP to brain FAAH. It is concluded that Flu-AM1 is a dual-action
      inhibitor of FAAH and COX that may be useful in exploring the optimal balance of
      effects on these two enzyme systems in producing peripheral alleviation of pain
      and inflammation in experimental models.

PMID- 24120371
TI  - Cannabinoids alter endothelial function in the Zucker rat model of type 2
      diabetes.
AB  - Circulating levels of anandamide are increased in diabetes, and cannabidiol
      ameliorates a number of pathologies associated with diabetes. The aim of the
      present study was to examine how exposure to anandamide or cannabidiol might
      affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age
      matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical
      dislocation and their arteries mounted on a myograph at 37  degrees C. Arteries
      were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and
      cumulative concentration-response curves to acetylcholine were constructed.
      Anandamide (10 uM, 2h) significantly improved the vasorelaxant responses to
      acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but
      not Zucker lean rats. By contrast, anandamide (1 uM, 2h) significantly blunted
      acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from
      Zucker Diabetic Fatty rats. Cannabidiol incubation (10 uM, 2h) improved
      acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and
      femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was
      greater in the Zucker Diabetic Fatty rat. These studies suggest that increased
      circulating endocannabinoids may alter vascular function both positively and
      negatively in type 2 diabetes, and that part of the beneficial effect of
      cannabidiol in diabetes may be due to improved endothelium-dependent
      vasorelaxation.

PMID- 24120372
TI  - C-type natriuretic peptide plasma levels are reduced in obese adolescents.
AB  - The high prevalence of obesity in children may increase the magnitude of lifetime
      risk of cardiovascular disease (CD). At present, explicit data for recommending
      biomarkers as routine pre-clinical markers of CD in children are lacking. C-type
      natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with
      heart failure, its plasma levels are related to clinical and functional disease
      severity. We have previously reported five different reference intervals for
      blood CNP as a function of age in healthy children; however, data on plasma CNP
      levels in obese children are still lacking. Aim of this study was to assess CNP
      levels in obese adolescents and verify whether they differ from healthy subjects.
      Plasma CNP was measured in 29 obese adolescents (age: 11.8 +/- 0.4 years; BMI:
      29.8 +/- 0.82) by radioimmunoassay and compared with the reference values of
      healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were
      significantly lower in the obese adolescents compared to the appropriate
      reference values (CNP: 3.4 +/- 0.2 vs 13.6 +/- 2.3 pg/ml, p<0.0001; BNP: 18.8 +/-
      2.6 vs 36.9 +/- 5.5 pg/ml, p=0.003). There was no significant difference between
      CNP values in males and females. As reported in adults, we observed lower plasma
      CNP and BNP levels in obese children, suggesting a defective natriuretic peptide
      system in these patients. An altered regulation of production, clearance and
      function of natriuretic peptides, already operating in obese adolescents, may
      possibly contribute to the future development of CD. Thus, the availability of
      drugs promoting the action of natriuretic peptides may represent an attractive
      therapeutic option to prevent CD.

PMID- 24120373
TI  - Spontaneous regression of primary progressive Hodgkin's lymphoma in a pediatric
      patient: a case report and review of literature.
AB  - Spontaneous regression of malignancies is a very rare phenomenon. Our research of
      existing literature yielded only 16 cases of Hodgkin's lymphoma which regressed
      spontaneously. The outcome of primary progressive Hodgkin's lymphoma is poor even
      with salvage chemotherapy and autologous bone marrow transplantation. Here we
      present a case of primary progressive Hodgkin's lymphoma, which regressed
      spontaneously after failure of salvage chemotherapy. To our knowledge, this is
      the first case report of primary progressive Hodgkin's lymphoma undergoing
      spontaneous regression. 

PMID- 24120374
TI  - Rotary ultrasonic machining of CFRP: a mechanistic predictive model for cutting
      force.
AB  - Cutting force is one of the most important output variables in rotary ultrasonic
      machining (RUM) of carbon fiber reinforced plastic (CFRP) composites. Many
      experimental investigations on cutting force in RUM of CFRP have been reported.
      However, in the literature, there are no cutting force models for RUM of CFRP.
      This paper develops a mechanistic predictive model for cutting force in RUM of
      CFRP. The material removal mechanism of CFRP in RUM has been analyzed first. The
      model is based on the assumption that brittle fracture is the dominant mode of
      material removal. CFRP micromechanical analysis has been conducted to represent
      CFRP as an equivalent homogeneous material to obtain the mechanical properties of
      CFRP from its components. Based on this model, relationships between input
      variables (including ultrasonic vibration amplitude, tool rotation speed,
      feedrate, abrasive size, and abrasive concentration) and cutting force can be
      predicted. The relationships between input variables and important intermediate
      variables (indentation depth, effective contact time, and maximum impact force of
      single abrasive grain) have been investigated to explain predicted trends of
      cutting force. Experiments are conducted to verify the model, and experimental
      results agree well with predicted trends from this model. 

PMID- 24120375
TI  - Transcriptome dynamics in early embryos of the ascidian, Ciona intestinalis.
AB  - Maternally provided mRNAs and proteins direct early development and activate the
      zygotic genome. Using microarrays, we examined the dynamics of transcriptomes
      during the early development of a basal chordate, Ciona intestinalis. Microarray
      analysis of unfertilized eggs, as well as 8-, and 16- and 32-cell embryos
      revealed that nearly half of the genes encoded in the genome were expressed
      maternally, and that approximately only one-fourth of these genes were expressed
      at similar levels among eggs obtained from different individuals. Genes encoding
      proteins involved in protein phosphorylation were enriched in this latter group.
      More than 90% of maternal RNAs were not reduced before the 16-cell stage when the
      zygotic developmental program begins. Additionally we obtained gene expression
      profiles of individual blastomeres from the 8- and 16-cell embryos. On the basis
      of these profiles, we concluded that the posterior-most localization, which has
      been reported for over 20 different transcripts, is the only major localization
      pattern of maternal transcripts. Our data also showed that maternal factors
      establish only nine distinct patterns of zygotic gene expression at the 16-cell
      stage. Therefore, one of the main developmental functions of maternally supplied
      information is to establish these nine distinct expression patterns in the 16
      cell embryo. The dynamics of transcriptomes in early-stage embryos provides a
      foundation for studying how maternal information starts the zygotic program. 

PMID- 24120376
TI  - Germ lineage properties in the urochordate Botryllus schlosseri - from markers to
      temporal niches.
AB  - The primordial germ cells (PGCs) in the colonial urochordate Botryllus schlosseri
      are sequestered in late embryonic stage. PGC-like populations, located at any
      blastogenic stage in specific niches, inside modules with curtailed lifespan,
      survive throughout the life of the colony by repeated weekly migration to newly
      formed buds. This cyclical migration and the lack of specific markers for PGC
      like populations are obstacles to the study on PGCs. For that purpose, we
      isolated the Botryllus DDX1 (BS-DDX1) and characterized it by normal expression
      patterns and by specific siRNA knockdown experiments. Expression of BS-DDX1
      concurrent with BS-Vasa, gamma-H2AX, BS-cadherin and phospho-Smad1/5/8, demarcate
      PGC cells from soma cells and from more differentiated germ cells lineages, which
      enabled the detection of additional putative transient niches in zooids.
      Employing BS-cadherin siRNA knockdown, retinoic acid (RA) administration or beta
      estradiol administration affirmed the BS-Vasa(+)BS-DDX1(+)BS-cadherin(+)gamma
      H2AX(+)phospho-Smad1/5/8(+) population as the B. schlosseri PGC-like cells. By
      striving to understand the PGC-like cells trafficking between transient niches
      along blastogenic cycles, CM-DiI-stained PGC-like enriched populations from late
      blastogenic stage D zooids were injected into genetically matched colonial ramets
      at blastogenic stages A or C and their fates were observed for 9 days. Based on
      the accumulated data, we conceived a novel network of several transient and short
      lived 'germ line niches' that preserve PGCs homeostasis, protecting these cells
      from the weekly astogenic senescence processes, thus enabling the survival of the
      PGCs throughout the organism's life. 

PMID- 24120377
TI  - Retinoid X receptor-mediated transdifferentiation cascade in budding tunicates.
AB  - In the budding tunicate, Polyandrocarpa misakiensis, retinoic acid (RA) applied
      to buds promotes transdifferentiation of somatic cells to form the secondary body
      axis. This study investigated the gene cascade regulating such RA-triggered
      transdifferentiation in tunicates. Genes encoding retinoic acid receptor (RAR)
      and retinoid X receptor (RXR) were induced during transdifferentiation, and they
      responded to all-trans RA or 13-cis RA in vivo, whereas 9-cis RA had the least
      effects, demonstrating differences in the ligand preference between budding
      tunicates and vertebrates. In contrast to RAR mRNA, RXR mRNA could induce
      transdifferentiation-related genes such as RXR itself, ERK, and MYC in an RA
      dependent manner and also induced beta-catenin (beta-CTN) RA-independently when
      it was introduced in vitro into tunicate cell lines that do not express
      endogenous RAR or RXR. Small interfering RNA (siRNA) of RXR dramatically
      attenuated not only RXR but also ERK and beta-CTN gene activities. An ERK
      inhibitor severely blocked wound healing and dedifferentiation. beta-CTN siRNA
      suppressed morphogenesis and redifferentiation, similar to RXR siRNA. These
      results indicate that in P. misakiensis, the main function of RA is to trigger
      positive feedback regulation of RXR rather than to activate RAR for unlocking
      downstream pathways for transdifferentiation. Our results may reflect an ancient
      mode of RA signaling in chordates. 

PMID- 24120378
TI  - Preeclamptic plasma induces transcription modifications involving the AP-1
      transcriptional regulator JDP2 in endothelial cells.
AB  - Preeclampsia is a pregnancy disorder characterized by hypertension and
      proteinuria. In preeclampsia, the placenta releases factors into the maternal
      circulation that cause a systemic endothelial dysfunction. Herein, we
      investigated the effects of plasma from women with preeclamptic and normal
      pregnancies on the transcriptome of an immortalized human umbilical vein
      endothelial cell line. The cells were exposed for 24 hours to preeclamptic or
      normal pregnancy plasma and their transcriptome was analyzed using Agilent
      microarrays. A total of 116 genes were found differentially expressed: 71 were up
      regulated and 45 were down-regulated. In silico analysis revealed significant
      consistency and identified four functional categories of genes: mitosis and cell
      cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic
      reticulum stress effectors. Moreover, several genes involved in vasoregulation
      and endothelial homeostasis showed modified expression, including EDN1, APLN,
      NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a
      significant overrepresentation of genes containing activation protein-1
      regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a
      repressor of activation protein-1. The role of JDP2 in the regulation of a subset
      of genes in the human umbilical vein endothelial cells was confirmed by siRNA
      inhibition. We characterized transcriptional changes induced by preeclamptic
      plasma on human umbilical vein endothelial cells, and identified, for the first
      time to our knowledge, JDP2 as a regulator of a subset of genes modified by
      preeclamptic plasma.

PMID- 24120379
TI  - Definition of the variables affecting efficacy of immunodepletion ex vivo of
      peripheral blood progenitor cell grafts by alemtuzumab (Campath in the bag).
AB  - The immunodepleting effects of alemtuzumab on peripheral blood progenitor cell
      (PBPC) grafts for stem cell transplantation need to be better defined. The
      optimal graft cell concentration, antibody dose, need for complement, and whether
      alemtuzumab is infused with the graft during transplantation remain unclear. PBPC
      from 6 normal allogeneic stem cell donors harvested by apheresis were first
      quantitated and the cellular content defined by flow cytometry. Mononuclear cells
      were then incubated with incremental concentrations of alemtuzumab (.00001,
      .0001, .001, and .01 mg/mL) for 30 minutes at 20 degrees C or in cell dose
      responses with 1, 5, and 10 * 10(6) mononuclear cells/mL added to a fixed dose of
      .001 mg/mL of alemtuzumab with or without a source of complement. Cells were
      enumerated and analyzed by flow cytometry before and after exposure to
      alemtuzumab. To determine the presence of unbound anti-CD52, the supernatant of
      the cell dose responses were tested using the ELISA assay. Selected CD34+ lineage
      negative cells were incubated with antibody at the same working concentrations
      and conditions and cultured in granulocyte-macrophage colony-forming unit assay.
      The colony numbers were compared with control cultures devoid of the antibody.
      Incremental concentrations of alemtuzumab led to a significant (2 log) reduction
      in CD3, CD4, and CD8 populations, which plateaued at .001 mg/mL. Addition of
      complement led to a further significant reduction in the CD4 and CD8 cells. The
      maximum CD4 (3 log) and CD8 (2 log) cell death was obtained at 10 * 10(6)
      cells/mL. Analysis of supernatants for soluble alemtuzumab by ELISA showed a
      significant reduction in the free antibody concentration when the cell number was
      increased from 1 to 10 * 10(6) cells/mL implying utilization/binding of the
      antibody by target cells. Incremental concentrations of alemtuzumab did not
      affect the number of granulocyte-macrophage colony-forming units. Alemtuzumab
      depletes all cells expressing the CD52 antigen and has higher activity on CD3,
      CD8, and particularly on CD4 cells, which are depleted in excess of 2 logs. From
      this study, we were able to derive that the optimal cell kill in the graft
      without detectable free alemtuzumab in the supernatant can be achieved with 1 mg
      of antibody per 100 mL containing 10 * 10(9) cells and active complement (AB
      serum).

PMID- 24120381
TI  - What is the optimal approach to major ABO-incompatible allogeneic stem cell
      transplantation?

PMID- 24120380
TI  - A phase 1 trial of eltrombopag in patients undergoing stem cell transplantation
      after total body irradiation.
AB  - Stem cell transplantation can be associated with significant periods of
      thrombocytopenia, necessitating platelet transfusions and contributing to the
      risk of bleeding. Thrombopoietin receptor agonists have been shown to enhance
      platelet counts in other clinical settings, and so a phase 1 clinical trial was
      conducted to assess the safety, pharmacokinetics, and maximum tolerated dose of
      once-daily eltrombopag in patients undergoing stem cell transplantation with
      conditioning regimens containing total body irradiation >=400 cGy. Eltrombopag
      was examined at dosage levels of 75, 150, 225, and 300 mg given orally once daily
      for 27 days, starting at 24 to 48 hours post-transplantation. Pharmacokinetic
      sampling was performed over a 24-hour period after the first dose of eltrombopag,
      as well as during the second week of treatment (steady-state). Nineteen patients
      were enrolled, 15 of whom completed protocol treatments. Three patients completed
      each dose level up to 225 mg, and 6 completed treatment at the highest dose of
      300 mg. Four patients were replaced because drug compliance was <75% of planned
      doses. No dose-limiting toxicities were observed in this heterogeneous post
      transplantation patient population. Common adverse events were related to
      standard stem cell transplantation. One episode of pulmonary embolus occurred 9
      days after discontinuation of eltrombopag, and the only other thromboembolic
      episode was a grade 2 catheter-related clot. We conclude that up to 27 days of
      once-daily dosing of eltrombopag after stem cell transplantation is well
      tolerated. 

PMID- 24120382
TI  - Clinical study evaluating the effect of bevacizumab on the severity of zoledronic
      acid-related osteonecrosis of the jaw in cancer patients.
AB  - This study aimed to evaluate the effect of bevacizumab (BVZ) on the severity of
      osteonecrosis of the jaw (ONJ) in a cohort of cancer patients treated with
      intravenous zoledronic acid (ZA). We reviewed 42 oncologic patients with ONJ
      between 2007 and 2010. Only patients with solids tumors and who had received ZA
      were included. Data analyses included age, sex, underlying disease, ZA and BVZ
      dosages, dental history and ONJ characteristics. Of the 42 ONJ patients treated
      with ZA, 10 also received BVZ. In the 10 ZA/BVZ patients, the mean duration of ZA
      treatment at the time of ONJ diagnosis was 12.4 months (+/-6.8), compared to 22.9
      months (+/-4.8) in the 32 patients who received ZA only (p<0.05). Cox's model
      analysis of the delay to ONJ diagnosis confirmed the impact of BVZ on ONJ
      diagnosis. In the ZA/BVZ-treated group, 7 (70%) patients developed spontaneous
      osteonecrosis. Multiple logistic regression analysis showed that ZA/BVZ is
      associated with increased risk of developing spontaneous ONJ (OR 6.07; 95% CI,
      [1.3-28.2], p<0.05). And finally, the number of ONJ lesions was increased in the
      ZA/BVZ-treated group compared to the ZA group (p<0.01). Other clinical conditions
      as type of tumor (prostate, breast...), cancer severity or other chemotherapy
      drugs also could be involved in ONJ evolution. However, this study demonstrates
      for the first time the potential negative influence of BVZ on the incidence and
      severity of ONJ in patients receiving ZA. Within the study limits, our results
      suggest that combination ZA/BVZ treatment may possibly predispose to the
      development of spontaneous and earlier ONJ.

PMID- 24120384
TI  - Update on long-term treatment with bisphosphonates for postmenopausal
      osteoporosis: a systematic review.
AB  - INTRODUCTION: Osteoporosis is a progressive skeletal disorder that requires long
      term treatment. However, there is little guidance regarding optimal treatment
      duration and what the treatment discontinuation and retreatment criteria should
      be. Given that bisphosphonates are the most commonly prescribed class of agent
      for the treatment of osteoporosis, we reviewed the long-term data relating to
      these therapies and discussed the considerations for using bisphosphonates in
      postmenopausal women with osteoporosis. METHODS: A PubMed search, using the
      search terms 'bisphosphonate', 'postmenopausal osteoporosis' and 'long term'
      and/or 'extension' was conducted in January 2013. Results from nine controlled
      studies that prospectively assessed alendronate, risedronate, ibandronate or
      zoledronic acid in women with postmenopausal osteoporosis were reviewed.
      FINDINGS: Clinical studies in postmenopausal women with osteoporosis showed that
      long-term use of bisphosphonates resulted in persistent antifracture and bone
      mineral density (BMD) increasing effects beyond 3 years of treatment. No
      unexpected adverse events were identified in these studies and the long-term
      tolerability profiles of bisphosphonates remain favorable. Data from the
      withdrawal extension studies of alendronate and zoledronic acid also showed that
      residual fracture benefits were seen in patients who discontinued treatment for 3
      to 5 years after an initial 3- to 5-year treatment period. BMD monitoring and
      fracture risk assessments should be conducted regularly to determine whether
      treatment could be stopped or should be reinitiated. Patients exhibiting T
      scores<-2.5 or who have suffered a new fracture while on treatment should
      continue treatment, while patients with T-scores>-2.5 could be considered for
      discontinuation of active treatment while undergoing continued monitoring of
      their bone health. The duration and potential discontinuation of treatment should
      be personalized for individual patients based on their response to treatment,
      fracture risk and comorbidities.

PMID- 24120383
TI  - Collagen advanced glycation inhibits its Discoidin Domain Receptor 2 (DDR2)
      mediated induction of lysyl oxidase in osteoblasts.
AB  - Diabetes increases the risk of bone fracture. Organic and inorganic bone
      extracellular matrix components determine bone strength. Previous studies
      indicate that in diabetes, glycation of collagen causes abnormal arrangements of
      collagen molecules and fragile bones. Diabetic bone fragility is additionally
      attributed to reduced levels of lysyl oxidase enzyme-dependent collagen cross
      links. The mechanism underlying the presence of lower enzymatic collagen cross
      links in diabetic bone has not been directly investigated. Here we determine in
      primary osteoblast cultures the regulation of lysyl oxidase protein by type I
      collagen and collagen modified by carboxymethylation (CML-collagen), a form of
      advanced glycation endproducts. Data indicate that non-glycated collagen up
      regulates lysyl oxidase levels both in primary non-differentiated and in
      differentiating mouse and rat osteoblast cultures, while CML-collagen fails to
      regulate lysyl oxidase in these cells. Collagen binding to Discoidin Domain
      Receptor-2 (DDR2) mediates lysyl oxidase increases, determined in DDR2 shRNA
      knockdown studies. DDR2 binding and activation were disrupted by collagen
      glycation, pointing to a mechanism for the diminished levels of lysyl oxidase and
      consequently low lysyl oxidase-derived cross-links in diabetic bone. Our studies
      indicate that collagen-integrin interactions may not play a major role in up
      regulating lysyl oxidase. Furthermore, non-collagenous ligands for the receptor
      for advanced glycation end products (RAGE) failed to alter lysyl oxidase levels.
      Taken together with published studies a new understanding emerges in which
      diabetes- and age-dependent inhibition of normal collagen-stimulated DDR2- and
      integrin-signaling, and independent advanced glycation-stimulated RAGE-signaling,
      each contributes to different aspects of diabetic osteopenia. 

PMID- 24120385
TI  - Peptic ulcer disease and mental illnesses.
AB  - OBJECTIVE: We evaluated the association between self-reported doctor-diagnosed
      peptic ulcer disease (PUD) and mental disorders in a representative cross
      sectional study conducted in 2010 in Singapore. METHOD: The sample comprised 6616
      community-dwelling individuals. Participants were asked about a previous history
      of doctor-diagnosed PUD. Assessment of mental disorders was performed using the
      World Mental Health Composite International Diagnostic Interview version 3.0.
      Quality of life was assessed using the EuroQoL 5D. RESULTS: The weighted
      prevalence of PUD was 1.58% (95% CI=1.13-2.02). In adjusted analyses, PUD was
      more common among people with anxiety disorders [obsessive compulsive disorders
      (OR 4.22, 95% CI 1.59-11.21), Generalized Anxiety Disorders (OR 9.25, 95% CI 2.43
      35.17), any anxiety disorders (OR 4.41, 95% CI 1.82-10.61)] and with any mood
      disorders (OR 2.66, 95% CI 1.08-6.53). PUD was associated with alcohol abuse and
      alcohol dependence, but not with smoking or nicotine dependence. Adjustment for
      nicotine and alcohol use attenuated the association of mood disorders with PUD,
      but not that of anxiety disorders. PUD was associated with reduced quality of
      life as measured on EuroQoL 5D, with further reduction in those with concomitant
      mental disorders. CONCLUSION: PUD was associated with anxiety disorders, and this
      association is not attenuated with adjustment for nicotine dependence or alcohol
      use disorder.

PMID- 24120386
TI  - Iodine deficiency in Egyptian autistic children and their mothers: relation to
      disease severity.
AB  - BACKGROUND AND AIMS: Because autism may be a disease of early fetal brain
      development, maternal hypothyroxinemia (HT) in early pregnancy secondary to
      iodine deficiency (ID) may be related to etiology of autism. The aim of the study
      was to assess the iodine nutritional status in Egyptian autistic children and
      their mothers and its relationship with disease characteristics. METHODS: Fifty
      autistic children and their mothers were studied in comparison to 50 controls.
      All subjects were subjected to clinical evaluation, measurement of urinary iodine
      (UI), free triiodothyronine (fT3), free tetraiodothyronine (fT4) and thyroid
      stimulating hormone (TSH) along with measurement of thyroid volume (TV). In
      addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment
      were done for all autistic children. RESULTS: Of autistic children and their
      mothers, 54% and 58%, respectively, were iodine deficient. None of the control
      children or their mothers was iodine deficient. UI was lower among autistic
      patients (p <0.001) and their mothers (p <0.001). Childhood Autism Rating Scale
      (CARS) score correlated negatively with UI (r = -0.94, p <0.001). Positive
      correlations were detected between autistic patients and their mothers regarding
      UI (r = 0.88, p <0.001), fT3 (r = 0.79, p = 0.03), fT4 (r = 0.91, p <0.001) and
      TSH (r = 0.69, p = 0.04). Autism had a significant risk for association with each
      of low UI (OR: 9.5, 95% CI: 2.15-33.8, p = 0.02) and intake of noniodized salt
      (OR: 6.82, 95% CI = 1.36-34.27, p = 0.031). CONCLUSIONS: ID is prevalent in
      Egyptian autistic children and their mothers and was inversely related to disease
      severity and could be related to its etiology.

PMID- 24120387
TI  - Influence of mesenchymal stem cells with endothelial progenitor cells in co
      culture on osteogenesis and angiogenesis: an in vitro study.
AB  - BACKGROUND AND AIMS: Bone is a highly vascularized tissue reliant on the close
      spatial and temporal connection between blood vessels and bone cells to maintain
      skeletal integrity. Considering the intricate connection between osteogenesis and
      angiogenesis, it is not surprising that communication between mesenchymal stem
      cells (MSCs) and endothelial progenitor cells (EPCs) is one of the most important
      cellular interactions that orchestrates bone formation. The aim of this study was
      to evaluate the interaction of co-cultured bone marrow-derived endothelial
      progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) in angiogenesis and
      osteogenesis in vitro. METHODS: MSCs and BM-EPCs were isolated from bone marrow
      of dogs' iliac crest using density gradient centrifugation combined with adhesion
      method and identified with surface markers, cell proliferation and
      immunocytochemistry in vitro. We used the direct contact method of MSCs and BM
      EPCs in a co-culture system. Co-cultured cells and non-co-cultured cells were
      examined using the alkaline phosphatase (ALP) activity assay, matrix
      mineralization assay, Matrigel 2D assay and gene expression. RESULTS: ALP
      activity and calcification of nodules significantly increased in the co-cultured
      cells compared with MSCs alone after day 3, and tubulogenic activity of the co
      cultured cells was also higher than BM-EPCs alone. Expression of bone and
      angiogenic markers were enhanced beyond expression levels of MSCs and BM-EPCs
      cultured alone. CONCLUSIONS: BM-EPCs co-cultured with MSCs can promote
      osteogenesis and angiogenesis. This co-cultured system may be broadly useful in
      engineering a variety of other tissue types.

PMID- 24120388
TI  - Effect of alpha-linolenic acid on streptozotocin-induced diabetic retinopathy
      indices in vivo.
AB  - BACKGROUND AND AIMS: Both oxidative stress and inflammation play a significant
      role in the pathobiology of diabetic retinopathy. Increased consumption of
      polyunsaturated fatty acids (PUFAs) may prevent or postpone the occurrence of
      diabetic retinopathy. Hence, the effect of alpha-linolenic acid (ALA), an
      essential fatty acid, on oxidative stress, inflammatory indices and production of
      vascular endothelial growth factor (VEGF) in streptozotocin-induced diabetic
      retinopathy indices in vivo was studied. METHODS: Serum and retina concentrations
      of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor
      (BDNF), interleukin-6 (IL-6), plasma and retina concentrations of lipid peroxides
      and antioxidant enzymes were estimated in streptozotocin (STZ)-induced diabetic
      animals. RESULTS: STZ-induced diabetic rats had significantly higher levels of
      VEGF in the serum and retina and IL-6 in the serum, whereas BDNF was lower in the
      serum, all of which reverted to near normal in ALA-treated diabetic animals. STZ
      treatment decreased serum glutathione peroxidase levels, which was restored to
      normal by both pre- and post-ALA treatment groups. CONCLUSIONS: STZ-induced
      changes in serum glutathione peroxidase, BDNF, VEGF and IL-6 that reverted to
      near control by ALA treatment, especially in ALA + STZ group, lending support to
      the concept that both oxidative stress and inflammation participate in DR and ALA
      treatment is of benefit in its prevention.

PMID- 24120389
TI  - Mutation screening for the EXT1 and EXT2 genes in Chinese patients with multiple
      osteochondromas.
AB  - BACKGROUND AND AIMS: Multiple osteochondromas (MO), an autosomal dominant
      skeletal disease, is characterized by the presence of multiple cartilage-capped
      bone tumors (exostoses). Two genes with mutations that are most commonly
      associated with MO have been identified as EXT1 and EXT2, which are Exostosin-1
      and Exostosin-2. In this study, a variety of EXT1 and EXT2 gene mutations were
      identified in ten Chinese families with MO. METHODS: We investigated ten
      unrelated Chinese families involving a total of 46 patients who exhibited typical
      features of MO. The coding exons of EXT1 and EXT2 were sequenced after PCR
      amplification in ten probands. Radiological investigation was conducted
      simultaneously. RESULTS: Nine mutations were identified, five in EXT1 and four in
      EXT2, of which three were de novo mutations and six were novel mutations. One
      proband carried mutations in both EXT1 and EXT2 simultaneously, and three
      probands, including one sporadic case and two familial cases, had no detectable
      mutations. CONCLUSIONS: Our findings are useful for extending the mutational
      spectrum in EXT1 and EXT2 and understanding the genetic basis of MO in Chinese
      patients.

PMID- 24120390
TI  - Molsidomine prevents cisplatin-induced hepatotoxicity.
AB  - BACKGROUND AND AIMS: Despite its beneficial effects, cisplatin has considerable
      nephrotoxic, ototoxic, neurotoxic and hepatotoxic side effects. It has been
      documented that reactive oxygen radical species are involved with the
      pathophysiology of cisplatin-induced hepatotoxicity. Molsidomine (MOL) can exert
      antioxidant and anti-inflammatory effects. Therefore, the current study was
      planned to determine the effects of cisplatin on the liver oxidant/antioxidant
      system and the possible protective effects of (MOL) on liver toxicity. METHODS:
      Animals were divided into four groups as follows: (1) control; (2) MOL; (3)
      cisplatin and (4) MOL plus cisplatin group. Biochemical and histopathological
      evaluations were performed on the extracted liver tissue. Also, serum levels of
      serum aspartate transaminase (AST) and serum alanine transaminase (ALT) were
      determined. RESULTS: Our results clearly indicated that liver antioxidant enzyme
      activities and ALT levels were significantly decreased, whereas lipid
      peroxidation and neutrophil accumulation were increased in the cisplatin-treated
      animals (5 mg/kg single dose, i.p.) compared to the control rats. MOL treatment
      (4 mg/kg/day, i.p.) for 3 consecutive days provided a significant protection
      against cisplatin-induced hazardous changes in the liver tissue. Our
      histopathological findings including caspase-3 activity were also in accordance
      with the biochemical results. CONCLUSIONS: We propose that MOL acts in the liver
      as a potent scavenger of free radicals, anti-inflammatory and anti-apoptotic
      effects to prevent the toxic effects of cisplatin, both at the biochemical and
      histopathological levels.

PMID- 24120391
TI  - Genetic variations in VDR associated with prostate cancer risk and progression in
      a Korean population.
AB  - Low levels of vitamin D are implicated as a potential risk factor for prostate
      cancer, and the vitamin D receptor (VDR) gene may be important in the onset and
      progression of prostate cancer. In this study, sequence variants in the VDR gene
      were investigated in a Korean study cohort to determine whether they are
      associated with prostate cancer risk. We evaluated the association between 47
      single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer risk
      as well as clinical characteristics (prostate-specific antigen level, clinical
      stage, pathological stage and Gleason score) in Korean men (272 prostate cancer
      patients and 173 benign prostatic hyperplasia patient who underwent a prostate
      biopsy, which was negative for malignancy) using unconditional logistic
      regression. The statistical analysis suggested that two VDR sequence variants
      (rs2408876 and rs2239182) had a significant association with prostate cancer risk
      (odds ratio [OR]. 1.41; p=0.03; OR, 0.73; p=0.05, respectively). Logistic
      analyses of the VDR polymorphisms with several prostate cancer related factors
      showed that several SNPs were significant; nine SNPs to PSA level, three to
      clinical stage, two to pathological stage, and three SNPs to the Gleason score.
      The results suggest that some VDR gene polymorphisms in Korean men might not only
      be associated with prostate cancer risk but also significantly related to
      prostate cancer-related risk factors such as PSA level, tumor stage, and Gleason
      score. However, current limitation for small cohort with not-healthy control
      group might have false positive effects; therefore it should be overcome via
      further large-scale validating studies. 

PMID- 24120392
TI  - GSTM1 and GSTT1 gene polymorphisms as major risk factors for bronchopulmonary
      dysplasia in a Chinese Han population.
AB  - Bronchopulmonary dysphasia (BPD) is a complex multifactorial disease with an
      obvious genetic predisposition. Oxidative stress plays an important role in its
      pathogenesis. Glutathione S-transferases (GSTs) detoxify metabolites produced by
      oxidative stress within the cell and protect the cells against injury. In the
      present study, the hypothesis that polymorphisms in the GSTM1 and GSTT1 genes are
      associated with BPD in Chinese Han infants was examined. Sixty infants with BPD
      and 100 gestational age and birth weight-matched preterm infants without BPD were
      recruited. Genotyping for GSTM1 and GSTT1 was performed by multiplex polymerase
      chain reaction (PCR). The GSTM1 null genotype was more prevalent in BPD infants
      (65.0%) than in the control subjects (48.0%), which yielded higher risk towards
      BPD (odds ratio (OR): 2.012, 95% confidence interval (CI)=1.040-3.892, p=0.037).
      There was no statistically significant association of GSTT1 genotype with BPD
      (OR: 1.691, 95% CI=0.884-3.236, p=0.111), although the frequency of GSTT1 null
      genotype was higher among the BPD subjects (60.0%) than in the control patients
      (47.0%). GSTM1 and GSTT1 double null genotype was also higher in BPD group
      (38.3%) than in controls (21.0%) with a higher risk towards BPD (OR: 2.338,
      95%CI=1.151-4.751, p=0.017). The results suggest that null genotypes of GSTM1 and
      GSTT1 genes may contribute to the development of BPD in our Chinese Han
      population.

PMID- 24120393
TI  - Antioxidant capacity responsible for a hypocholesterolemia is independent of
      dietary cholesterol in adult rats fed rice protein.
AB  - Dietary cholesterol and aging are major risk factors to accelerate oxidation
      process for developing hypercholesterolemia. The major aim of this study is to
      elucidate the effects of rice protein on cholesterol level and oxidative stress
      in adult rats fed with and without cholesterol. After 2 weeks of feeding, hepatic
      and plasma contents of cholesterol, reduced glutathione (GSH), oxidized
      glutathione (GSSG), malondialdehyde (MDA) and protein carbonyl (PCO) were
      measured. In liver, total antioxidative capacity (T-AOC), activities of
      antioxidant enzymes (total superoxide dismutase, T-SOD; catalase, CAT),
      glutathione metabolizing enzyme activities and gene expression levels (gamma
      glutamylcysteine synthetase, gamma-GCS; glutathione reductase, GR; glutathione
      peroxidase, GPx) were determined. Under cholesterol-free/enriched dietary
      condition, T-AOC, activities of T-SOD and CAT, glutathione metabolism related
      enzymes' activities and mRNA levels (gamma-GCS, GR and GPx) were effectively
      stimulated by rice proteins as compared to caseins. Compared with caseins, rice
      proteins significantly increased hepatic and plasma GSH contents, whereas hepatic
      and plasma accumulations of MDA, PCO and GSSG were significantly reduced by rice
      protein-feedings. As a result, the marked reductions of cholesterol in the plasma
      and in the liver were observed in adult rats fed rice proteins with and without
      cholesterol. The present study demonstrates that the hypocholesterolemic effect
      of rice protein is attributable to inducing antioxidative response and depressing
      oxidative damage in adult rats fed cholesterol-free/enriched diets. Results
      suggest that the antioxidant capability involved in the hypocholesterolemic
      action exerted by rice protein is independent of dietary cholesterol during adult
      period.

PMID- 24120394
TI  - MiR-375, a microRNA related to diabetes.
AB  - MiR-375 is an important small non-coding RNA that is specifically expressed in
      islet cells of the pancreas. miR-375 is required for normal pancreatic genesis
      and influences not only beta-cell mass but also alpha-cell mass. miR-375 is also
      important to glucose-regulated insulin secretion through the regulation of the
      expression of Mtpn and Pdk1 genes. When human embryonic stem cells (hESCs)
      differentiate into endodermal lineages, miR-375 is highly expressed in the
      definitive endoderm, which suggests that miR-375 may have a distinct role in
      early development. miR-375 plays an important role in the complex regulatory
      network of pancreatic development, which could be regulated by pancreatic genes,
      such as NeuroD1, Ngn3, Pdx1 and Hnf6; additionally, miR-375 regulates genes
      related to pancreas development, cell growth and proliferation and insulin
      secretion genes to exert its function. Because of the special role of miR-375, it
      may be a potential target to treat diabetes. Antagonising miR-375 may enhance the
      effects of exendin-4 in patients, and controlling the expression of miR-375 could
      assist mature hESCs-derived beta-cells.

PMID- 24120395
TI  - Computational identification of human long intergenic non-coding RNAs using a GA
      SVM algorithm.
AB  - Long intergenic non-coding RNAs (lincRNAs) are a new type of non-coding RNAs and
      are closely related with the occurrence and development of diseases. In previous
      studies, most lincRNAs have been identified through next-generation sequencing.
      Because lincRNAs exhibit tissue-specific expression, the reproducibility of
      lincRNA discovery in different studies is very poor. In this study, not including
      lincRNA expression, we used the sequence, structural and protein-coding potential
      features as potential features to construct a classifier that can be used to
      distinguish lincRNAs from non-lincRNAs. The GA-SVM algorithm was performed to
      extract the optimized feature subset. Compared with several feature subsets, the
      five-fold cross validation results showed that this optimized feature subset
      exhibited the best performance for the identification of human lincRNAs.
      Moreover, the LincRNA Classifier based on Selected Features (linc-SF) was
      constructed by support vector machine (SVM) based on the optimized feature
      subset. The performance of this classifier was further evaluated by predicting
      lincRNAs from two independent lincRNA sets. Because the recognition rates for the
      two lincRNA sets were 100% and 99.8%, the linc-SF was found to be effective for
      the prediction of human lincRNAs.

PMID- 24120396
TI  - Association between health literacy and child and adolescent obesity.
AB  - OBJECTIVE: We tested the association between child and parental health literacy
      (HL) and odds of child and adolescent obesity. METHODS: We conducted an anonymous
      cross-sectional survey of a convenience sample of English-speaking child-parent
      dyads. Newest Vital Sign (NVS) measured HL. We used multivariable logistic
      regression to test adjusted association between child and parental NVS and
      obesity. Analyses were stratified for school-aged children (aged 7-11) vs.
      adolescents (aged 12-19). RESULTS: We surveyed 239 child-parent dyads. Median
      child age was 11 [inter-quartile range 9-13]; 123 (51%) were male; 84% Medicaid
      recipients; 27% obese. For children, the odds of obesity [adjusted odds ratio
      (95% confidence interval)] decreased with higher parent NVS [0.75 (0.56,1.00)]
      and increased with parent obesity [2.53 (1.08,5.94)]. For adolescents, odds of
      obesity were higher for adolescents with the lowest category of NVS [5.00 (1.26,
      19.8)] and older parental age [1.07 (1.01,1.14)] and lower for Medicaid
      recipients [0.21 (0.06,0.78)] and higher parental education [0.38 (0.22,0.63)].
      CONCLUSION: Obesity in school-aged children is associated with parental factors
      (obesity, parental HL); obesity in adolescents is strongly associated with the
      adolescent's HL. PRACTICE IMPLICATIONS: Strategies to prevent and treat obesity
      should consider limited HL of parents for child obesity and of adolescents for
      adolescent obesity.

PMID- 24120397
TI  - A validated new histological classification for intervertebral disc degeneration.
AB  - Histology is an important outcome variable in basic science and pre-clinical
      studies regarding intervertebral disc degeneration (IVD). Nevertheless, an
      adequately validated histological classification for IVD degeneration is still
      lacking and the existing classifications are difficult to use for inexperienced
      observers. OBJECTIVE: Therefore the aim of this study was to develop and to
      validate a new histological classification for IVD degeneration. Moreover, the
      new classification was compared to the frequently used non-validated
      classification. METHODS: The new classification was applied to human IVD
      sections. The sections were scored twice by two independent inexperienced
      observers, twice by two experienced IVD researchers and once by a pathologist.
      For comparison, the sections were also scored according to the classification
      described by Boos et al. by two experienced IVD researchers. Macroscopic grading
      according Thompson et al., glycosaminoglycan (GAG) content and age were used for
      validation. RESULTS: The new classification had an excellent intra- and a good
      inter-observer reliability. Intraclass Correlation Coefficients (ICC) were 0.83
      and 0.74, respectively. Intra- and inter-observer reliability were comparable for
      experienced and inexperienced observers. Statistically significant correlations
      were found between the new classification, macroscopic score, GAG content in the
      nucleus pulposus (NP) and age; Correlation coefficient (CC) 0.79, -0.62 and 0.68,
      respectively. The CCs of the Boos classification were all lower compared to the
      new classification. CONCLUSION: the new histological classification for IVD
      degeneration is a valid instrument for evaluating IVD degeneration in human IVD
      sections and is suitable for inexperienced and experienced researchers.

PMID- 24120398
TI  - Prescription of inhalers in asthma and COPD: towards a rational, rapid and
      effective approach.
AB  - Inhaled medication is the cornerstone of the pharmacological treatment of
      patients with asthma and COPD. The major two classes of inhaled medication
      include corticosteroids (ICS) and bronchodilators. There is a wide diversity in
      molecules in both classes. Moreover, there is a wide variation in delivery
      systems. The correct use of inhalers is not granted and patients often incur in
      many mistakes when using pMDIs and DPIs, despite repeated instructions. A better
      matching between patient and device could be accomplished if the physician is
      aware of: (1) the patient characteristics (disease, severity, fluctuation in
      airflow obstruction, etc); (2) what class of medication is indicated; (3) where
      in the lung the medication should be delivered; and, (4) how this can be best
      achieved by a given device in this specific patient. We focus on the prescription
      of pMDIs and DPIs at the GP office or at the outpatient clinic of the hospital,
      and we propose an evidence based approach enabling the caregiver to make a
      rational choice in only a few minutes by just considering the following four
      simple questions: Who?, What? Where? and How? (the so-called 3W-H approach). 

PMID- 24120399
TI  - Proposal for effective treatment of Shiga toxin-producing Escherichia coli
      infection in mice.
AB  - Previously, we reported that minocycline, kanamycin and norfloxacin improved the
      survival rate in the E32511 model that we developed (FEMS Immunol Med Microbiol
      26, 101-108, 1999), but fosfomycin did not. In this study, we investigated the
      effectiveness of azithromycin (AZM) against Stx2d-producing EHEC O91:H21 strain
      B2F1 or Stx2c-producing Escherichia coli strain E32511 treated with mitomycin C
      in vivo. Recently, we reported the effectiveness of AZM in our model and AZM
      strongly inhibited the release of Stx2c from E32511 in vitro (PLOS ONE e58959,
      2013). However, it was very difficult to completely eliminate E32511 in the mouse
      feces by treatment with AZM alone. In this report, only AZM or Daio effectively
      promoted survival of mice infected with B2F1 compared to untreated mice.
      Furthermore, Daio inhibited the colonization of GFP-expressing B2F1 in the mouse
      intestine. Similarly, a combination of AZM and Daio in the E32511-infected mice
      reduced E32511 in the mouse feces and significantly improved survival. 

PMID- 24120400
TI  - Narp knockout mice show normal reactivity to novelty but attenuated recovery from
      neophobia.
AB  - Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive
      behavior, which are associated with abnormal reactivity to a novel stimulus. To
      assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a
      neophobia procedure. Both Narp KO and WT mice showed a similar decrease in
      consumption upon initial exposure to a novel flavor, but Narp KO mice did not
      increase consumption with subsequent exposures to the novel flavor like the WT
      mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show
      deficits in adapting behavior to reflect the updated value of a stimulus. 

PMID- 24120401
TI  - Dopaminergic mechanisms underlying catalepsy, fear and anxiety: do they interact?
AB  - Haloperidol is a dopamine D2 receptor antagonist that induces catalepsy when
      systemically administered to rodents. The haloperidol-induced catalepsy is a
      state of akinesia and rigidity very similar to that seen in Parkinson's disease.
      There exists great interest in knowing whether or not some degree of emotionality
      underlies catalepsy. If so, what kind of emotional distress would permeate such
      motor disturbance? This study is an attempt to shed some light on this issue
      through an analysis of ultrasound vocalizations (USVs) of 22 kHz, open-field
      test, and contextual conditioned fear in rats with some degree of catalepsy
      induced by haloperidol. Systemic administration of haloperidol caused catalepsy
      and decreased exploratory activity in the open-field. There was no difference in
      the emission of USVs between groups during the catalepsy or the exploratory
      behavior in the open-field test. In the contextual conditioned fear, when
      administered before training session, haloperidol did not change the emission of
      USVs or the freezing response. When administered before testing session,
      haloperidol enhanced the freezing response and decreased the emission of USVs on
      the test day. These findings suggest that the involvement of dopaminergic
      mechanisms in threatening situations depends on the nature of the aversive
      stimulus. Activation of D2 receptors occurs in the setting up of adaptive
      responses to conditioned fear stimuli so that these mechanisms seem to be
      important for the emission of 22 kHz USVs during the testing phase of the
      contextual conditioned fear, but not during the training session or the open
      field test (unconditioned fear stimuli). Catalepsy, on the other hand, is the
      result of the blockage of D2 receptors in neural circuits associated to motor
      behavior that appears to be dissociated from those directly linked to dopamine
      mediated neural mechanisms associated to fear.

PMID- 24120403
TI  - The role of dendritic cells in the pathogenesis of cigarette smoke-induced
      emphysema in mice.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is an important lung and airway
      disease which affects the lives of around 200 million people worldwide. The
      pathological hallmark of COPD is emphysema and bronchiolitis and is based on the
      inflammatory response of the innate and adaptive immune system to the inhalation
      of toxic particles and gases. The inflamed airways of COPD patients contain
      several inflammatory cells including neutrophils, macrophages, T lymphocytes, and
      dendritic cells (DC). The potential role of DCs as mediators of inflammation in
      the airways of smokers and COPD patients is poorly understood. The current study
      investigated the role of DC subsets in an animal model of cigarette smoke-induced
      lung emphysema through the expansion or depletion of DC subsets. Expansion of
      both myeloid DC (mDC) and plasmacytoid DC (pDC) by Flt3L treatment induced a
      decline in macrophage numbers and increased the levels of fibroblast growth
      factor (FGF) and vascular endothelial growth factor (VEGF) in the bronchoalveolar
      lavage (BAL) fluid of smoke-exposed animals. The increase in the mean linear
      intercept (Lm) following Flt3L treatment was decreased by pDC depletion. In
      conclusion, pharmacological modulation of DC subsets may have an effect on the
      development of airway responses and emphysema as indicated by the decline in
      macrophage numbers and the increase in FGF and VEGF levels in the bronchoalveolar
      lavage fluid. Moreover, the depletion of pDCs decreased the Lm which might
      suggest a role for pDC in the pathogenesis of lung emphysema. 

PMID- 24120404
TI  - Accuracy of the SenseWear Armband Mini and the BodyMedia FIT in resistance
      training.
AB  - OBJECTIVES: To examine the validity and reliability of the SenseWear Armband Mini
      and BodyMedia FIT in comparison to the Cosmed K4b(2) portable for assessing
      energy expenditure during resistance training. DESIGN: Lab based validation and
      reliability study. METHODS: Eleven males and 7 females (age = 22.7 +/- 4.5 years)
      completed two resistance-training sessions. Total energy expenditure was
      simultaneously assessed by the SenseWear Armband Mini, BodyMedia FIT and Cosmed
      K4b(2) portable. The resistance-training sessions involved 3 sets of 10
      repetitions for 9 different exercises. The weight lifted was 70% of the
      participants 1 repetition max with 90-s rest intervals. Validity and re-test
      reliability was assessed using Pearson correlations and mean change (%) +/- 90%
      confidence limits and log transformed typical error measurements (TEMCV%).
      RESULTS: A very large correlation was identified for total energy expenditure
      (Kcal) from both the SenseWear Armband Mini and BodyMedia FIT in comparison to
      the Cosmed K4b(2) portable (r = 0.77 and r = 0.78, respectively) and an almost
      perfect correlation was observed for total energy expenditure (Kcal) between the
      SenseWear Armband Mini and BodyMedia FIT (r = 0.97). A small percent mean change
      for the SenseWear Armband Mini (23.7%) and a trivial percent mean change for the
      BodyMedia FIT (13.8%) was observed in comparison to the Cosmed K4b(2) portable
      with a tendency to underestimate total energy expenditure. The SenseWear Armband
      Mini and BodyMedia FIT displayed an almost perfect correlation for total energy
      expenditure (Kcal) between sessions (r = 0.96 and r = 0.97, respectively) whilst
      TEMCV% of 5.1 and 4.3, respectively were observed. CONCLUSIONS: The SenseWear
      Armband Mini and BodyMedia FIT provide a valid and reliable measure of energy
      expenditure during resistance training. There was no significant difference in
      validity or reliability observed between the SenseWear Armband Mini and BodyMedia
      FIT.

PMID- 24120402
TI  - Adolescence is a period of development characterized by short- and long-term
      vulnerability to the rewarding effects of nicotine and reduced sensitivity to the
      anorectic effects of this drug.
AB  - This study compared nicotine intake and changes in food intake and weight gain in
      naive adolescent, naive adult, and adult rats that were exposed to nicotine
      during adolescence. An extended intravenous self-administration (IVSA) model was
      used whereby rats had 23-hour access to saline or increasing doses of nicotine
      (0.03, 0.06, and 0.09 mg/kg/0.1 mL infusion) for 4-day intervals separated by 3
      day periods of abstinence. Rats began IVSA as adolescents (PND 32-34) or adults
      (PND 75). A separate group of rats was exposed to nicotine via osmotic pumps (4.7
      mg/kg) for 14 days during adolescence and then began nicotine IVSA as adults (PND
      75). The rats that completed the nicotine IVSA regimen were also tested for
      nicotine-seeking behavior during extinction. The results revealed that nicotine
      intake was highest in adolescents followed by adults that were pre-exposed to
      nicotine during adolescence as compared to naive adults. A similar pattern of
      nicotine-seeking behavior was observed during extinction. In contrast to nicotine
      intake, naive adults displayed robust appetite and weight suppressant effects of
      nicotine, an effect that was absent in adolescents and adults that were pre
      exposed to nicotine during adolescence. Our findings suggest that adolescence is
      a unique period of enhanced vulnerability to the reinforcing effects of nicotine.
      Although adolescents gain weight faster than adults, the food intake and weight
      suppressant effects of nicotine are reduced during adolescence. Importantly, our
      findings suggest that adolescent nicotine exposure produces long-lasting
      consequences that enhance nicotine reward and promote tolerance to the anorectic
      effects of this drug.

PMID- 24120405
TI  - Refining a complex diagnostic construct: subtyping Dysthymia with the Shedler
      Westen Assessment Procedure-II.
AB  - OBJECTIVE: We sought to determine whether meaningful subtypes of Dysthymic
      patients could be identified when grouping them by similar personality profiles.
      METHOD: A random, national sample of psychiatrists and clinical psychologists
      (n=1201) described a randomly selected current patient with personality pathology
      using the descriptors in the Shedler-Westen Assessment Procedure-II (SWAP-II),
      completed assessments of patients' adaptive functioning, and provided DSM-IV Axis
      I and II diagnoses. RESULTS: We applied Q-factor cluster analyses to those
      patients diagnosed with Dysthymic Disorder. Four clusters were identified-High
      Functioning, Anxious/Dysphoric, Emotionally Dysregulated, and Narcissistic. These
      factor scores corresponded with a priori hypotheses regarding diagnostic
      comorbidity and level of adaptive functioning. We compared these groups to
      diagnostic constructs described and empirically identified in the past
      literature. CONCLUSIONS: The results converge with past and current ideas about
      the ways in which chronic depression and personality are related and offer an
      enhanced means by which to understand a heterogeneous diagnostic category that is
      empirically grounded and clinically useful.

PMID- 24120406
TI  - Comorbidity of personality disorders in mood disorders: a meta-analytic review of
      122 studies from 1988 to 2010.
AB  - BACKGROUND: A meta-analysis was conducted to identify the proportions of comorbid
      personality disorders (PD) in mood disorders. METHODS: We found 122 empirical
      papers published in the period 1980-2010 on participants having mood disorders in
      addition to a comorbid PD. Mood disorders were classified as bipolar disorders
      (BD), major depressive disorders (MDD) and dysthymic disorders (DYS). Several
      moderators were coded as well. RESULTS: The risk of having at least one comorbid
      PD (any PD) was high across all three mood disorders (BD=.42, MDD=.45), but
      highest in DYS (.60). Cluster B and C PDs were most frequent in BD, while cluster
      C PDs dominated in MDD and DYS. Among the specific PDs, the paranoid (.11 versus
      .07/.05), borderline (.16 versus .14/.13), histrionic (.10 versus .06/.06) and
      obsessive-compulsive (.18 versus .09/.12) PDs occurred more frequently in BD
      versus MDD/DYS, whereas the avoidant PD (.22 versus .12/.16) was most frequent in
      DYS versus BD/MDD. Moderator analyses showed higher comorbidity when diagnoses
      were based on questionnaires versus clinical interviews, DSM-III-R versus DSM-IV,
      more women were included or the duration of the disorder was longer. Age of onset
      yielded mixed results. LIMITATIONS: Blind rating of diagnoses was recorded, but
      was employed in too few studies to be usable as an indication of diagnostic
      validity. CONCLUSIONS: Personality disorders are common in mood disorders.
      Implications of the identified moderators as well as the new DSM-5 diagnostic
      system are considered.

PMID- 24120407
TI  - Contrasting temporal trend discovery for large healthcare databases.
AB  - With the increased acceptance of electronic health records, we can observe the
      increasing interest in the application of data mining approaches within this
      field. This study introduces a novel approach for exploring and comparing
      temporal trends within different in-patient subgroups, which is based on
      associated rule mining using Apriori algorithm and linear model-based recursive
      partitioning. The Nationwide Inpatient Sample (NIS), Healthcare Cost and
      Utilization Project (HCUP), Agency for Healthcare Research and Quality was used
      to evaluate the proposed approach. This study presents a novel approach where
      visual analytics on big data is used for trend discovery in form of a regression
      tree with scatter plots in the leaves of the tree. The trend lines are used for
      directly comparing linear trends within a specified time frame. Our results
      demonstrate the existence of opposite trends in relation to age and sex based
      subgroups that would be impossible to discover using traditional trend-tracking
      techniques. Such an approach can be employed regarding decision support
      applications for policy makers when organizing campaigns or by hospital
      management for observing trends that cannot be directly discovered using
      traditional analytical techniques. 

PMID- 24120408
TI  - Pyrosequencing reveals higher impact of silver nanoparticles than Ag+ on the
      microbial community structure of activated sludge.
AB  - Although the antimicrobial capabilities of silver nanoparticles (AgNPs) are
      widely reported, their impacts on ecologically important microbial communities
      are not well understood. AgNPs released from consumer products will likely enter
      sewer systems and wastewater treatment plants, where they would encounter (and
      potentially upset) activated sludge (AS), a complex ecosystem containing a
      variety of bacteria. Herein we address the effects of AgNPs and Ag(+) ions on the
      microbial community structure of AS, using pyrosequencing technology. Compared to
      Ag(+) amendment, a lower AgNP concentration resulted in a more pronounced effect
      on AS community structure, possibly reflecting a higher propensity of Ag(+) than
      AgNPs to be scavenged by inorganic ligands and organic matter. Furthermore, AgNPs
      decreased the abundance of nitrifying bacteria, which would hinder N removal, and
      damaged AS floc structure, which could affect sludge clarification and recycling.
      Overall, although released Ag(+) is known to be the critical effector of the
      antimicrobial activity of AgNPs, the nanoparticles apparently delivered Ag(+) to
      bacteria more effectively and exerted more pronounced microbial population shifts
      that would hinder some wastewater treatment processes.

PMID- 24120409
TI  - Quantitation of glutathione and its oxidation products in erythrocytes by
      multiple-label stable-isotope dilution.
AB  - A multiple-label stable isotope dilution assay for quantifying glutathione (GSH),
      glutathione disulfide (GSSG), and glutathione sulfonic acid in erythrocytes was
      developed. As the internal standards, [(13)C3,(15)N]glutathione,
      [(13)C4,(15)N2]glutathione disulfide, and [(13)C3,(15)N]glutathione sulfonic acid
      were used. Analytes and internal standards were detected by LC-MS/MS after
      derivatization of GSH with iodoacetic acid and dansylation of all compounds under
      study. The calibration functions for all analytes relative to their respective
      isotopologic standards revealed slopes close to 1.0 and negligible intercepts. As
      various labelings of the standards for GSH and GSSG were used, their simultaneous
      quantitation was possible, although GSH was partly oxidized to its disulfide
      during analysis. The degree of this artifact formation of GSSG was calculated
      from the abundance of the mixed disulfide formed from unlabeled GSH and its
      respective standard. Thus, the detected GSSG amount could be corrected for the
      artifact amount. In this way, the amount of GSSG in erythrocytes was found to be
      less than 0.5% of the GSH concentration. Similar to GSSG, the detected amount of
      glutathione sulfonic acid was found to be formed at least in part during the
      analytical process, but the degree could not be quantified. 

PMID- 24120410
TI  - Digital image analysis approach for lipid droplet size quantitation of Oil Red O
      stained cultured cells.
AB  - A simple approach was developed for the quantification of lipid droplet size and
      frequency distribution in images acquired by standard light microscopy. Oil Red O
      stained cell images were thresholded for the lipid droplet signal using the
      freely available imaging software ImageJ. Watershed algorithms allowed analyzing
      the area of each individual lipid droplet. The method was validated by the
      decrease in lipid droplet size of 3T3-L1 adipocytes on lowered glucose
      availability associated with reduced glycerol-3-phosphate dehydrogenase activity
      and reduced transcription of lipid droplet size markers. This approach can be
      easily applied using standard laboratory equipment without requiring expensive
      and complex instrumentation. 

PMID- 24120411
TI  - Squeezed flow preconcentration for probe tip biosensors.
AB  - The preconcentration of analytes improves sensing using probe tips. In this work,
      we report a method based on creating a squeeze flow between a cylinder and
      circular coverslip to preconcentrate material at the liquid-gas interface while
      allowing a probe tip to be readily inserted there. In verification tests using
      enhanced green fluorescent protein, this capacity is proven. We estimated a 9.7
      times increase in probability for fluorophores to be picked up at the tip using
      inference from fluorescence intensity distributions found. The method is
      expeditious, simple, and inexpensive, and it does not require any electrical
      energy source to operate. 

PMID- 24120412
TI  - Secondary flow in peripheral vascular prosthetic grafts using vector Doppler
      imaging.
AB  - Prosthetic grafts are used for the treatment of peripheral arterial disease. Re
      stenosis in the distal anastomosis of these grafts is a common reason for graft
      occlusion. The role of local hemodynamics in development of neo-intimal
      hyperplasia is well known. A new graft design has been proposed for the induction
      of optimized spiral flow in the host vessel. The secondary flow motions induced
      by this graft were compared with those of a control device. Both types of grafts
      were connected with vessel mimic and positioned in ultrasound flow phantoms with
      identical geometry. Constant flow rates were applied. Data collected in the cross
      sectional view distal from the graft outflow and dual-beam vector Doppler was
      applied to create 2-D velocity maps. A single-spiral flow pattern was found for
      the flow-modified graft, and double or triple spirals for the control graft. In
      plane maximum velocity was greater for the flow-modified graft than for the
      control device. 

PMID- 24120413
TI  - Assessment of resting-state blood flow through anterior cerebral arteries using
      trans-cranial doppler recordings.
AB  - Trans-cranial Doppler (TCD) recordings are used to monitor cerebral blood flow in
      the main cerebral arteries. The resting state is usually characterized by the
      mean velocity or the maximum Doppler shift frequency (an envelope signal) by
      insonating the middle cerebral arteries. In this study, we characterized cerebral
      blood flow in the anterior cerebral arteries. We analyzed both envelope signals
      and raw signals obtained from bilateral insonation. We recruited 20 healthy
      patients and conducted the data acquisition for 15 min. Features were extracted
      from the time domain, the frequency domain and the time-frequency domain. The
      results indicate that a gender-based statistical difference exists in the
      frequency and time-frequency domains. However, no handedness effect was found. In
      the time domain, information-theoretic features indicated that mutual dependence
      is higher in raw signals than in envelope signals. Finally, we concluded that
      insonation of the anterior cerebral arteries serves as a complement to middle
      cerebral artery studies. Additionally, investigation of the raw signals provided
      us with additional information that is not otherwise available from envelope
      signals. Use of direct trans-cranial Doppler raw data is therefore validated as a
      valuable method for characterizing the resting state. 

PMID- 24120414
TI  - Comparative study of acoustic radiation force impulse imaging with real-time
      elastography in differential diagnosis of thyroid nodules.
AB  - The aims of this study were to evaluate whether acoustic radiation force impulse
      (ARFI) imaging of the thyroid gland and thyroid nodules yields reliable results
      and to compare the values of ARFI imaging with those of real-time elastography
      (RTE) in the differential diagnosis of thyroid nodules. RTE and ARFI were
      performed in 30 patients with 58 thyroid nodules. The results were compared with
      pathologic findings. Receiver operating characteristic curves were drawn to
      evaluate the diagnostic results. The area under the curve for RTE (0.78) was
      smaller than that for ARFI (0.94) (p < 0.01). ARFI imaging of thyroid tissue
      yields more reliable results than RTE. 

PMID- 24120417
TI  - Neurapraxia and not neuropraxia.

PMID- 24120415
TI  - Correlation of cognitive function with ultrasound strain indices in carotid
      plaque.
AB  - Instability in carotid vulnerable plaque can generate cerebral micro-emboli,
      which may be related to both stroke and eventual cognitive abnormality. Strain
      imaging to detect plaque vulnerability based on regions with large strain
      fluctuations, with arterial pulsation, may be able to determine the risk of
      cognitive impairment. Plaque instability may be characterized by increased strain
      variations over a cardiac cycle. Radiofrequency signals for ultrasound strain
      imaging were acquired from the carotid arteries of 24 human patients using a
      Siemens Antares with a VFX 13-5 linear array transducer. These patients underwent
      standardized cognitive assessment (Repeatable Battery for the Assessment of
      Neuropsychological Status [RBANS]). Plaque regions were segmented by a
      radiologist at end-diastole using the Medical Imaging Interaction Toolkit. A
      hierarchical block-matching motion tracking algorithm was used to estimate the
      cumulated axial, lateral and shear strains within the imaging plane. The maximum,
      minimum and peak-to-peak strain indices in the plaque computed from the mean
      cumulated strain over a small region of interest in the plaque with large
      deformations were obtained. The maximum and peak-to-peak mean cumulated strain
      indices over the entire plaque region were also computed. All strain indices were
      then correlated with RBANS Total performance. Overall cognitive performance
      (RBANS Total) was negatively associated with values of the maximum strain and the
      peak-to-peak for axial and lateral strains, respectively. There was no
      significant correlation between the RBANS Total score and shear strain and strain
      indices averaged over the entire identified plaque for this group of patients.
      However, correlation of maximum lateral strain was higher for symptomatic
      patients (r = -0.650, p = 0.006) than for asymptomatic patients (r = -0.115, p =
      0.803). On the other hand, correlation of maximum axial strain averaged over the
      entire plaque region was significantly higher for asymptomatic patients (r = 
      0.817, p = 0.016) than for symptomatic patients (r = -0.224, p = 0.402). The
      results reveal a direct relationship between the maximum axial and lateral strain
      indices in carotid plaque and cognitive impairment. 

PMID- 24120418
TI  - Effects of FK-506 and CTLA4--Ig on nerve allografts in mice.
AB  - The purpose of this study is to evaluate the effects of FK-506 and cytotoxic T
      lymphocyte-associated antigen-4 immunoglobulin fusion protein (CTLA4--Ig) on
      nerve allografts. Adult male inbred C3H mice (mean weight, 25 g) surgically
      received 8 mm posterior tibial nerve defects, and donor nerve allografts from
      donor male C57BL mice were implanted. The experimental animals were divided into
      five groups of 12 animals each that were distinguished from each other by
      administration of FK-506 and CTLA4--Ig, that is, isografts interposed in the gap
      between contralateral posterior tibial nerves (group A, positive control);
      allografts from C57BL mice implanted without administering any treatment (group
      B, negative control); allografts from C57BL mice implanted and FK-506 injections
      administered (group C); allografts from C57BL mice implanted and CTLA4--Ig
      injections administered (group D); and allografts from C57BL mice implanted and
      FK-506 and CTLA4--Ig injections administered (group E). Postoperative walking
      track functional analysis and histomorphometric studies were then conducted. Data
      were statistically analysed using the Kruskal-Wallis test. Compared with the
      negative control (group B), mice treated with both FK-506 and CTLA4--Ig (group E)
      demonstrated better results at 3 weeks post operation. Similar values were
      observed in all groups, and there were no statistical differences at 6 weeks post
      operation. Our results demonstrate that a co-administration of FK-506 and CTLA4-
      Ig results in functional and histomorphometric recovery that is superior to that
      seen in the absence of these medications.

PMID- 24120416
TI  - Functional characterization of an AQP0 missense mutation, R33C, that causes
      dominant congenital lens cataract, reveals impaired cell-to-cell adhesion.
AB  - Aquaporin 0 (AQP0) performs dual functions in the lens fiber cells, as a water
      pore and as a cell-to-cell adhesion molecule. Mutations in AQP0 cause severe lens
      cataract in both humans and mice. An arginine to cysteine missense mutation at
      amino acid 33 (R33C) produced congenital autosomal dominant cataract in a Chinese
      family for five generations. We re-created this mutation in wild type human AQP0
      (WT-AQP0) cDNA by site-directed mutagenesis, and cloned and expressed the mutant
      AQP0 (AQP0-R33C) in heterologous expression systems. Mutant AQP0-R33C showed
      proper trafficking and membrane localization like WT-AQP0. Functional studies
      conducted in Xenopus oocytes showed no significant difference (P > 0.05) in water
      permeability between AQP0-R33C and WT-AQP0. However, the cell-to-cell adhesion
      property of AQP0-R33C was significantly reduced (P < 0.001) compared to that of
      WT-AQP0, indicated by cell aggregation and cell-to-cell adhesion assays. Scrape
      loading assay using Lucifer Yellow dye showed reduction in cell-to-cell adhesion
      affecting gap junction coupling (P < 0.001). The data provided suggest that this
      mutation might not have caused significant alterations in protein folding since
      there was no obstruction in protein trafficking or water permeation. Reduction in
      cell-to-cell adhesion and development of cataract suggest that the conserved
      positive charge of Extracellular Loop A may play an important role in bringing
      fiber cells closer. The proposed schematic models illustrate that cell-to-cell
      adhesion elicited by AQP0 is vital for lens transparency and homeostasis. 

PMID- 24120419
TI  - Reducing wound healing complications of Wise pattern breast reduction with the
      inverted "V" modification.

PMID- 24120421
TI  - Peri-infusional adverse reactions to rituximab in patients with non-Hodgkin's
      lymphoma.
AB  - BACKGROUND AND AIMS: Rituximab is effective in the treatment of B-cell lymphoid
      malignances and some autoimmune diseases. Most patients receiving the first
      infusion of rituximab experience symptoms that decrease with subsequent
      infusions. It is assumed that the first dose of rituximab should be infused
      slowly during a 6-h period and during 4-h periods subsequently. The aim of the
      study was to evaluate the frequency and severity of adverse reactions to
      rituximab in patients with non-Hodgkin's lymphoma. METHODS: This was an intensive
      pharmacovigilance prospective, observational, open labeled, multicenter cohort
      study conducted in 12 hospitals. Adults requiring treatment with rituximab (375
      mg/m(2) body surface area) alone or with chemotherapy were included. Adverse
      reactions were graded according to the National Cancer Institute scale, whereas
      causality was established using the Naranjo algorithm. Infusions were classified
      as fast (0-90 min) and slow (>91 min). Fast infusions were used to analyze the
      associated adverse reactions. RESULTS: We included 550 adult patients. Total
      infusion episodes were 1,749 and 52 adverse reactions were reported in 22
      patients (4%). Thirty-one of 52 adverse reactions occurred during the first
      infusion. The risk of adverse reactions was lower with the fast infusions (10/52
      adverse reactions [19.23%]). All adverse effects were mild. Twenty-three adverse
      effects were possibly related to rituximab. CONCLUSIONS: Rituximab can be infused
      at a fast rate without an increase in adverse reactions. Peri-infusional adverse
      reactions are similar to those described for other populations but the incidence
      rate is lower. Rituximab has a favorable safety profile in patients with non
      Hodgkin's lymphoma.

PMID- 24120420
TI  - [Aspergillus species in hospital environments with pediatric patients in critical
      condition].
AB  - BACKGROUND: Aspergillus is a group of opportunistic fungi that cause infections,
      with high morbimortality in immunosuppressed patients. Aspergillus fumigatus is
      the most frequent species in these infections, although the incidence of other
      species has increased in the last few years. AIMS: To evaluate the air fungal
      load and the diversity of Aspergillus species in hospitals with pediatric
      patients in critical condition. METHODS: The Intensive Care Unit and Burns Unit
      of a pediatric hospital were sampled every 15 days during the autumn and spring
      seasons. The air samples were collected with SAS Super 100((r)) and the surface
      samples were collected by swab method. RESULTS: The UFC/m(3) counts found
      exceeded the acceptable levels. The UFC/m(3) and the diversity of Aspergillus
      species found in the Intensive Care Unit were higher than those found in the
      Burns Unit. The fungal load and the diversity of species within the units were
      higher than those in control environments. The use of both methods -SAS and swab-
      allowed the detection of a higher diversity of species, with 96 strains of
      Aspergillus being isolated and 12 species identified. The outstanding findings
      were Aspergillus sydowii, Aspergillus niger, Aspergillus flavus, Aspergillus
      terreus and Aspergillus parasiticus, due to their high frequency. Aspergillus
      fumigatus, considered unacceptable in indoor environments, was isolated in both
      units. CONCLUSIONS: Aspergillus was present with high frequency in these units.
      Several species are of interest in public health for being potential pathogenic
      agents. Air control and monitoring are essential in the prevention of these
      infections.

PMID- 24120422
TI  - Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast
      cancer?
AB  - PURPOSE: Neoadjuvant chemotherapy (NAC) in breast cancer is currently used not
      only for locally advanced tumors, but also for large operable tumors when breast
      preservation is considered. It also provides the opportunity to evaluate
      chemotherapy tumor response. Our aim was to correlate the relative change in the
      standardized uptake value (SUV) of (18)F-2-fluoro-2-deoxy-D-glucose positron
      emission tomography (FDG-PET/CT) with pathologic response after NAC. METHODS: We
      prospectively evaluated 40 patients with invasive ductal breast carcinomas from
      February 2010 to December 2011. FDG-PET/CT was performed at baseline and after
      the second cycle of NAC. All patients underwent surgery after NAC. Pathologic
      response was evaluated according to Residual Cancer Burden (RCB) index. RESULTS:
      The mean age was 41.9 years. Median primary tumor size was 6 cm. Pathologic
      complete response (pCR) was obtained in 12 (30%) patients. The tumor baseline
      mean maximum SUV (SUV(max)), and after second cycle were: 8.97 (sd.4.3) and 4.07
      (sd.3.2), respectively. The relative change (DeltaSUV) after the second course of
      NAC was significantly higher for patients with pCR (-81.58%) when compared to the
      non-pCR patients (-40.18%) (p = 0.001). The optimal DeltaSUV threshold that
      discriminates between pCR and non-pCR was -71.8% (83.3% sensitivity; 78.5%
      specificity). Moreover, the optimal DeltaSUV threshold to discriminate between
      NAC responders and non-responders was -59.1% (68% sensitivity; 75.0%
      specificity). CONCLUSIONS: Our data suggest that the FDG-PET/CT DeltaSUV after
      the second course of NAC can predict pathological response in ductal breast
      carcinomas, and potentially identify a subgroup of non-responding patients for
      whom ineffective chemotherapy should be avoided. SYNOPSIS: Breast cancer is the
      most frequently diagnosed cancer in women. The indications for neoadjuvant
      chemotherapy are increasing. Early information on chemotherapy response is
      crucial and methods that predict the therapeutic effectiveness might avoid
      potentially ineffective chemotherapies in non-responding patients.

PMID- 24120423
TI  - Adolescent cannabinoid treatment negatively affects reproductive behavior in
      female rats.
AB  - Sex differences in the neurobehavioral effects of chronic cannabinoid exposure
      suggest that gonadal hormones may modify cannabinoid activity. The current
      experiment assessed the impact of combined cannabinoid and estradiol treatment in
      ovariectomized, adolescent female rats on subsequent adult sexual behavior.
      Female Long-Evans rats were administered daily injections of either the
      cannabinoid agonist, CP 55,940 (0.4 mg/kg), or vehicle from post-natal day (PND)
      40-49. Half of each treatment group also received daily injections of estradiol
      (50 MUg/kg) or sesame oil vehicle from PND 39-49. Beginning on PND 74, subjects'
      reproductive behavior, including receptivity, proceptivity, and pacing, was
      assessed via a fifteen-minute paced mating test. There were significant main
      effects of estradiol treatment on rate of hop-darts emitted, number of arena
      crossings, and ejaculations received during the paced mating test. Overall,
      estradiol-treated females produced higher and more typical levels of sexual
      behavior. There were significant interactions between hormone and cannabinoid
      treatment on lordosis quotient, percentage of exits following male sexual
      stimulation, and contact-return latency for intromissions. Adolescent cannabinoid
      treatment detrimentally impacted the display of female receptivity and pacing,
      but only within estradiol-treated subjects. We discuss possible interpretations
      of these results, including potential mechanisms by which adolescent cannabinoid
      exposure might disrupt the normal development of female reproductive behavior.

PMID- 24120424
TI  - Role of p53 in the cellular response following oleic acid accumulation in Chang
      liver cells.
AB  - Abnormal accumulation of fatty acids triggers the harmful cellular response
      called lipotoxicity. In this study, we investigated the cellular response
      following accumulation of oleic acid (OA), a monounsaturated fatty acid, in human
      Chang liver cells. OA droplets were distributed freely in the cytoplasm and/or
      degraded within lysosomes. OA exposure increased ATP production and concomitantly
      dilated mitochondria. At 24h after OA exposure, cell viability decreased slightly
      and was coupled with a reduction in mitochondrial Ca(2+) concentration, the
      alteration in cell viability was also associated with the generation of reactive
      oxygen species and changes in the cell cycle. Moreover, OA treatment increased
      the expression of autophagy- and apoptotic cell death-related proteins in a dose
      dependent manner. Furthermore, we investigated the role of p53, a tumor
      suppressor protein, in the cellular response elicited by OA accumulation. OA
      induced changes in cell viability and ATP production were rescued to control
      levels when cells were pretreated with pifithrin-alpha (PTA), a p53 inhibitor. By
      contrast, the expressions of LC3-II and perilipin, proteins required for
      lipophagy, were down-regulated by PTA pretreatment. Taken together, our results
      suggest that p53 plays a key role in the cellular response elicited by OA
      accumulation in Chang liver cells. 

PMID- 24120425
TI  - Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich
      cultured rat hepatocytes.
AB  - Alpha-naphthylisothiocyanate (ANIT) induces intra-hepatic cholestasis mixed with
      hepatocellular injury mainly by bile ductular damage. However, its direct effect
      on hepatic parenchymal cells (hepatocytes) is unclear. Sandwich-cultured rat
      hepatocytes (SCRH) were applied to clarify this question. Though cytotoxicity was
      not observed (0-180 MUM) in ANIT-treated SCRH, metabonomics analysis of the
      hepatocytes revealed a shift in the metabolic pattern and a decrease in cellular
      cholesterol level, accompanied by an increase in total bile acids after 48 h ANIT
      (5-45 MUM) treatment. To assess the function of major hepatic bile acid
      transporters, the accumulation and efflux of [D-Pen(2,5)]-enkephalin (DPDPE), 5
      (and 6)-carboxy-2',7'-dichlorofluorescein (CDF) diacetate promoiety and deuterium
      labeled sodium taurocholate (d8-TCA) were measured. ANIT incubation for either 30
      min or 48 h led to dose-dependent decreases in the biliary excretion index (BEI)
      of DPDPE and CDF, as well as the intracellular accumulation of d8-TCA, CDF and
      DPDPE. The basolateral efflux of d8-TCA was also decreased with its BEI barely
      changed. mRNA expression of multiple uptake transporters and bile acid
      synthesizing enzymes was down-regulated after 48 h incubation. In conclusion,
      ANIT could directly induce retention of bile acids in hepatocytes by inhibiting
      the function of bile acid transporters, which might contribute to its cholestatic
      effect.

PMID- 24120426
TI  - Factors affecting graded and ungraded memory loss following hippocampal lesions.
AB  - This review evaluates three current theories--Standard Consolidation (Squire &
      Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple
      Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their
      ability to account for the role of the hippocampus in recent and remote memory in
      animals. Evidence, based on consistent findings from tests of spatial memory and
      memory for acquired food preferences, favours the transformation account, but
      this conclusion is undermined by inconsistent results from studies that measured
      contextual fear memory, probably the most commonly used test of hippocampal
      involvement in anterograde and retrograde memory. Resolution of this issue may
      depend on exercising greater control over critical factors (e.g., contextual
      environment, amount of pre-exposure to the conditioning chamber, the number and
      distribution of foot-shocks) that can affect the representation of the memory
      shortly after learning and over the long-term. Research strategies aimed at
      characterizing the neural basis of long-term consolidation/transformation, as
      well as other outstanding issues are discussed.

PMID- 24120427
TI  - Fear generalization in humans: impact of feature learning on conditioning and
      extinction.
AB  - Little is known about the role of discrete stimulus features in the regulation of
      fear. This study examined the effects of feature learning on the acquisition and
      extinction of fear conditioning. Human participants were fear conditioned to a
      yellow triangle (CS+) using an electrical shock. We manipulated feature learning
      through differential conditioning. The nonconditioned control stimulus (CS-) was
      a red triangle in one group (Color-Relevant), but a yellow circle in the other
      group (Shape-Relevant). Next, two generalization stimuli were tested that shared
      the shape- or color-feature with the CS+ (a blue triangle and a yellow square).
      Online shock-expectancy ratings and skin conductance responding showed that the
      CS- determined the pattern of fear generalization: the same-color stimulus
      elicited more fear in Group Color-Relevant, versus the same-shape stimulus in
      group Shape-Relevant. Furthermore, extinguishing these two generalization stimuli
      had no detectable effect on fear of the CS+. These results show that fear
      generalization is influenced by feature learning through differential
      conditioning, and that exposures to different features of a stimulus are not
      sufficient to extinguish fear of that stimulus as a whole. 

PMID- 24120428
TI  - Upregulation of SOX9 in Glial (Muller) cells in retinal light damage of rats.
AB  - Recent evidence suggests that SOX9 [sex-determining region Y (SRY) box 9], a
      transcription factor, plays a pivotal role in acquired diseases, revealing its
      importance in roles beyond development. However, whether SOX9, which is one of
      the key regulators of retinal Muller cell development, also participates in the
      pathological process of retinal degenerative diseases remains unknown. In the
      present study, we hypothesized that SOX9 was upregulated in Muller cells in
      retinal degeneration. Retinal light damage (LD) was used as a model for retinal
      degeneration. On day 3, 7, 14, 21, and 28 after LD in adult Sprague Dawley (SD)
      rats, the spatial distribution of SOX9 in the retina was observed by
      immunohistochemistry; the expression levels of SOX9 were measured by real-time
      PCR and Western blot analysis. Moreover, type 1 collagen (COL1) and cone-rod
      homeobox (CRX) protein levels, which are two downstream targets of SOX9, were
      also assessed by Western blot analysis. Colabeling for SOX9 and glutamine
      synthetase (GS), a specific Muller cell maker, indicated that SOX9 was expressed
      in the Muller cell nucleus in both control and LD groups. Significantly enhanced
      SOX9 expression was observed as early as day 3 after LD, and it persisted for at
      least 28 days. COL1 and CRX protein levels also increased after LD. Our study
      demonstrates the involvement of SOX9 in acquired retinal degeneration triggered
      by LD, which might provide novel insights into possible molecular mechanisms that
      would account for the involvement of Muller cells in retinal degenerative
      diseases. 

PMID- 24120429
TI  - N-benzylcinnamide protects rat cultured cortical neurons from beta-amyloid
      peptide-induced neurotoxicity.
AB  - The pathogenesis of Alzheimer's disease involves an amyloid beta-peptide (Abeta)
      induced cascade of elevated oxidative damage and inflammation. The present study
      investigates the protective effects and the underlying mechanisms of N
      benzylcinnamide (PT-3), purified from Piper submultinerve. Against Abeta-induced
      oxidative stress and inflammation in rat primary cortical cell cultures. Pre
      treatment with 10-00nM PT-3 significantly attenuated neuronal cell death induced
      by 10MUM Abeta1-42. PT-3 was found to enhance cell viability through a
      significant reduction in the level of reactive oxygen species, down-regulated
      expression of pro-apoptotic activated caspase-3 and Bax, increased expression of
      anti-apoptotic Bcl-2, and mitigation of Abeta-induced morphological alterations.
      Regarding its effects on inflammatory responses, PT-3 pre-treatment decreased the
      expression of pro-inflammatory cytokines IL-1beta and IL-6. The mechanisms of PT
      3 neuronal protection against inflammation may be associated with the mitogen
      activated protein kinases (MAPK) pathway. Abeta1-42-induced phosphorylation of
      JNK and p38 MAPK was inhibited by pretreatment with PT-3 in a dose-dependent
      manner. However, phosphorylation of ERK1/2 was not affected by either PT-3 or
      Abeta1-42. PT-3 did not stimulate Akt phosphorylation, which was inhibited by
      Abeta1-42. These findings suggest that PT-3 protects neurons from Abeta1-42
      induced neurotoxicity through its anti-apoptotic, anti-oxidative, and anti
      inflammatory properties with inhibition of JNK and p38 MAPK phosphorylation as
      the potential underlying mechanism. 

PMID- 24120431
TI  - Concurrent visual and tactile steady-state evoked potentials index allocation of
      inter-modal attention: a frequency-tagging study.
AB  - We investigated effects of inter-modal attention on concurrent visual and tactile
      stimulus processing by means of stimulus-driven oscillatory brain responses, so
      called steady-state evoked potentials (SSEPs). To this end, we frequency-tagged a
      visual (7.5Hz) and a tactile stimulus (20Hz) and participants were cued, on a
      trial-by-trial basis, to attend to either vision or touch to perform a detection
      task in the cued modality. SSEPs driven by the stimulation comprised stimulus
      frequency-following (i.e. fundamental frequency) as well as frequency-doubling
      (i.e. second harmonic) responses. We observed that inter-modal attention to
      vision increased amplitude and phase synchrony of the fundamental frequency
      component of the visual SSEP while the second harmonic component showed an
      increase in phase synchrony, only. In contrast, inter-modal attention to touch
      increased SSEP amplitude of the second harmonic but not of the fundamental
      frequency, while leaving phase synchrony unaffected in both responses. Our
      results show that inter-modal attention generally influences concurrent stimulus
      processing in vision and touch, thus, extending earlier audio-visual findings to
      a visuo-tactile stimulus situation. The pattern of results, however, suggests
      differences in the neural implementation of inter-modal attentional influences on
      visual vs. tactile stimulus processing. 

PMID- 24120430
TI  - Meditation's impact on default mode network and hippocampus in mild cognitive
      impairment: a pilot study.
AB  - Those with high baseline stress levels are more likely to develop mild cognitive
      impairment (MCI) and Alzheimer's Disease (AD). While meditation may reduce stress
      and alter the hippocampus and default mode network (DMN), little is known about
      its impact in these populations. Our objective was to conduct a "proof of
      concept" trial to determine whether Mindfulness Based Stress Reduction (MBSR)
      would improve DMN connectivity and reduce hippocampal atrophy among adults with
      MCI. 14 adults with MCI were randomized to MBSR vs. usual care and underwent
      resting state fMRI at baseline and follow-up. Seed based functional connectivity
      was applied using posterior cingulate cortex as seed. Brain morphometry analyses
      were performed using FreeSurfer. The results showed that after the intervention,
      MBSR participants had increased functional connectivity between the posterior
      cingulate cortex and bilateral medial prefrontal cortex and left hippocampus
      compared to controls. In addition, MBSR participants had trends of less bilateral
      hippocampal volume atrophy than control participants. These preliminary results
      indicate that in adults with MCI, MBSR may have a positive impact on the regions
      of the brain most related to MCI and AD. Further research with larger sample
      sizes and longer-follow-up are needed to further investigate the results from
      this pilot study. 

PMID- 24120432
TI  - Chemokines as peripheral pain mediators.
AB  - Multiple lines of evidence support the notion that much if not most chronic pain
      is dependent on on-going peripheral activity in nociceptors. This is not to say
      that central changes are unimportant, only that much of the central change is
      supported by a peripheral drive. This begs the question of what causes this
      peripheral drive. In some instances, particularly in association with peripheral
      nerve injury, nociceptors may become spontaneously active because of alterations
      in ion channel function or expression. But in most cases nociceptor activity
      arises because of the actions of peripheral mediators released by injured or
      damaged tissue. Some of these mediators are well known, such as the prostanoids.
      Others have more recently been identified, such as nerve growth factor (NGF).
      However, the limited efficacy of existing analgesic therapies strongly suggests
      that other important pain mediators exist. Here we discuss the evidence that a
      family of secreted proteins, the chemokines - well known for their actions in
      regulating immune cell migration - also play an important role in sustaining
      abnormal nociceptor activity in persistent pain states.

PMID- 24120433
TI  - The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits
      in a rat post-status epilepticus model.
AB  - Ciliary neurotrophic growth factor is considered a potential therapeutic agent
      for central nervous system diseases. We report first in vivo data of the ciliary
      neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status
      epilepticus model. Cintrofin prevented long-term alterations in the number of
      doublecortin-positive neuronal progenitor cells and attenuated the persistence of
      basal dendrites. In contrast, Cintrofin did neither affect acute status
      epilepticus-associated alterations in hippocampal cell proliferation and
      neurogenesis nor reveal any relevant effect on seizure activity. Whereas status
      epilepticus caused a significant disturbance in spatial learning in reversed
      peptide-treated rats, the performance of Cintrofin-treated rats did not differ
      from controls. The study confirms that Cintrofin comprises an active sequence
      mimicking effects of its parent molecule. While the data argue against an
      antiepileptogenic effect, they indicate a putative disease-modifying impact of
      Cintrofin. 

PMID- 24120434
TI  - Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine
      exposure in mice.
AB  - Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine
      exposure and attenuates development of behavioral sensitization produced by
      repeated cocaine exposure. An important question that has not yet been answered
      is whether or not CTX reduces behavioral sensitization to cocaine in cases in
      which the antibiotic is administered only during the period of cocaine absence
      that follows repeated cocaine exposure and precedes reintroduction to cocaine. We
      investigated this question using C57BL/6 mice. Mice pretreated with cocaine
      (15mg/kg*14 days) and then challenged with cocaine (15mg/kg) after 30 days of
      cocaine absence displayed sensitization of locomotor activity. For combination
      experiments, CTX injected during the 30 days of cocaine absence attenuated
      behavioral sensitization produced by cocaine challenge. In the case in which CTX
      was injected together with cocaine for 14 days, development of behavioral
      sensitization to cocaine challenge was also reduced. CTX attenuated the increase
      in locomotor activity produced by acute cocaine exposure; however, its efficacy
      was dependent on the dose of cocaine as inhibition was detected against 30mg/kg,
      but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates
      locomotor activity produced by acute and repeated cocaine exposure and counters
      cocaine's locomotor activating properties in a paradigm in which the antibiotic
      is injected during the period of forced cocaine absence that follows repeated
      cocaine exposure. 

PMID- 24120435
TI  - Differential distributions of neuropeptides in hypothalamic paraventricular
      nucleus neurons projecting to the rostral ventrolateral medulla in the rat.
AB  - The hypothalamic paraventricular nucleus (PVN) exerts a major regulatory role in
      the endocrine and the autonomic system. It has anatomically and functionally
      distinct cell populations, one of which projects to the rostral ventrolateral
      medulla (PVN-RVLM) and are involved in the sympathetic regulation of the
      cardiovascular system. To investigate the expression and the distributional
      patterns of peptides in the PVN-RVLM neurons of rats, we used single cell RT-PCR
      analysis in combination with retrograde tracing. Approximately 80% of PVN-RVLM
      neurons expressed oxytocin (OT) and 60% expressed dynorphin (Dyn). There were
      differential distributions of peptides between the subdivisions of PVN-RVLM
      neurons. The posterior parvocellular subdivision predominantly expressed OT; the
      dorsal cap subdivision contained much less vasopressin (VP) compared to other
      subdivisions. In addition, PVN-RVLM neurons preponderantly co-expressed multiple
      peptides. These results suggest that peptides may contribute to elaborate
      responses of PVN to various stimuli. 

PMID- 24120436
TI  - Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm
      fetal sheep.
AB  - Preterm brain injury is partly associated with hypoxia-ischemia starting before
      birth. Excessive nitric oxide production during HI may cause nitrosative stress,
      leading to cell membrane and mitochondrial damage. We therefore tested the
      hypothesis that therapy with a new, selective neuronal nitric oxide synthase
      (nNOS) inhibitor, JI-10 (0.022mg/kg bolus, n=8), given 30min before 25min of
      complete umbilical cord occlusion was protective in preterm fetal sheep at 101
      104day gestation (term is 147days), compared to saline (n=8). JI-10 had no effect
      on fetal blood pressure, heart rate, carotid and femoral blood flow, total EEG
      power, nuchal activity, temperature or intracerebral oxygenation on near-infrared
      spectroscopy during or after occlusion. JI-10 was associated with later onset of
      post-asphyxial seizures compared with saline (p<0.05), and attenuation of the
      subsequent progressive loss of cytochrome oxidase (p<0.05). After 7days recovery,
      JI-10 was associated with improved neuronal survival in the caudate nucleus
      (p<0.05), but not the putamen or hippocampus, and more CNPase positive
      oligodendrocytes in the periventricular white matter (p<0.05). In conclusion,
      prophylactic nNOS inhibition before profound asphyxia was associated with delayed
      onset of seizures, slower decline of cytochrome oxidase and partial white and
      gray matter protection, consistent with protection of mitochondrial function. 

PMID- 24120438
TI  - Smad3 deficiency increases cortical and hippocampal neuronal loss following
      traumatic brain injury.
AB  - Transforming growth factor-beta (TGF-beta) signaling is involved in pathological
      processes following brain injury. TGF-beta signaling through Smad3 contributes
      significantly to the immune response and glial scar formation after brain injury.
      However, TGF-beta is also neuroprotective, suggesting that Smad3 signaling may
      also be involved in neuroprotection after injury. We found expression of the TGF
      beta type II receptor (TbetaRII) and Smad3 protein to be strongly and rapidly
      induced in neurons in the ipsilateral cortex and CA1 region of the hippocampus
      after stab wound injury. In contrast, astrocytic expression of TbetaRII and Smad3
      was induced more slowly. Comparison of the response of wild-type and Smad3 null
      mice to cortical stab wound injury showed a more pronounced loss of neuronal
      viability in Smad3 null mice. Neuronal density was more strongly reduced in Smad3
      null mice than in wild-type mice at 1 and 3days post lesion in both the
      ipsilateral cortex and hippocampal CA1 region. Fluoro-Jade B, TUNEL staining, and
      cleaved caspase-3 staining also demonstrated increased neuronal degeneration at
      early time points after injury in the ipsilateral hemisphere in Smad3 null mice.
      Taken together, our results suggest that TGF-beta cytokine family signaling
      through Smad3 protects neurons in the damaged cortex and hippocampus at early
      time points after injury. 

PMID- 24120437
TI  - Combination therapy in a transgenic model of Alzheimer's disease.
AB  - The pathological accumulation of the beta-amyloid protein (Abeta) has been
      closely associated with synaptic loss and neurotoxicity contributing to cognitive
      dysfunction in Alzheimer's disease (AD). Oligomers of Abeta42 appear to be the
      most neurotoxic form. Two of the most promising attempts to reduce Abeta
      accumulation have been with scyllo-inositol, an inositol steroisomer, that
      stabilizes Abeta42 peptide and prevents it from progressing to oligomers and
      fibrils and R-flurbiprofen, a purified enantiomer of the classical racemic non
      steroidal anti-inflammatory drugs (NSAID), flurbiprofen, that retains the ability
      to specifically lower Abeta42. In the present study we evaluated the effects of
      scyllo-inositol and the combination treatment of scyllo-inositol+R-flurbiprofen
      on amyloid pathology and hippocampal-dependent memory function in 5XFAD mice, a
      model of Abeta pathology characterized by an enormous production of Abeta42. Our
      expectations were that the combination treatment of scyllo-inositol+R
      flurbiprofen would have an additive effect in preventing Abeta accumulation and
      that cognition would be improved. Mice treated with scyllo-inositol exhibit 41
      and 35% reduction in the deposition of the amyloid plaques stained by antibody
      against Abeta42 and Abeta40 respectively. Scyllo-inositol was not more effective
      when combined with R-flurbiprofen for the measures tested. Scyllo-inositol
      treated mice performed significantly better at the radial arm water maze (RAWM)
      task than untreated and scyllo-inositol+R-flurbiprofen treated mice. 

PMID- 24120439
TI  - Mutation of the TBCE gene causes disturbance of microtubules in the auditory
      nerve and cochlear outer hair cell degeneration accompanied by progressive
      hearing loss in the pmn/pmn mouse.
AB  - The progressive motor neuronopathy (pmn/pmn) mouse, an animal model for a fast
      developing human motor neuron disorder, is additionally characterized by
      simultaneous progressive sensorineural hearing loss. The gene defect in the
      pmn/pmn mouse is localized to a missense mutation in the tubulin-specific
      chaperone E (TBCE) gene on mouse chromosome 13, which is one of the five tubulin
      specific chaperons involved in tubulin folding and dimerization. The missense
      mutation leads to a disturbance of tubulin structures in the auditory nerve and a
      progressive outer hair cell loss due to apoptosis, which is accompanied by highly
      elevated ABR-thresholds and loss of DPOAEs. In addition the TBCE protein is
      selectively expressed in the outer hair cells and the transcellular processes of
      the inner pillar cells in the cochlea of control and pmn/pmn mouse. We conclude
      from our study that the mutation of the TBCE gene affects the auditory nerve and
      the cochlear hair cells simultaneously, leading to progressive hearing loss. This
      animal model will give the chance to test possible therapeutic strategies in
      special forms of hearing loss, in which the auditory nerve and the cochlear hair
      cells are simultaneously affected. 

PMID- 24120440
TI  - Sulforaphane ameliorates the development of experimental autoimmune
      encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation
      in mice.
AB  - Sulforaphane (SFN) is an organosulfur compound present in vegetables and has
      potent anti-oxidant and anti-inflammatory activities. This study was aimed at
      investigating the effect of treatment with SFN on inflammation and oxidative
      stress, and the potential mechanisms underlying the action of SFN in experimental
      autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN
      significantly inhibited the development and severity of EAE in mice, accompanied
      by mitigating inflammatory infiltration and demyelination in the spinal cord of
      mice. The protective effect of SFN was associated with significantly improved
      distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression,
      preserving the blood-brain barrier. Furthermore, the protection of SFN was also
      related to decreased levels of oxidative stress in the brains of mice by enhanced
      activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and
      NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17
      responses and enhanced IL-10 responses. Our data indicated that treatment with
      SFN inhibited EAE development and severity in mice by its anti-oxidant activity
      and antagonizing autoimmune inflammation. Our findings suggest that SFN and its
      analogues may be promising reagents for intervention of multiple sclerosis and
      other autoimmune diseases. 

PMID- 24120441
TI  - Methadone, a contested substance: Danish methadone policy in the 1970s.
AB  - BACKGROUND: During the 1970s in Denmark, there was a great deal of controversy
      about the role of methadone in Danish drug policy. At stake were not just
      epistemological issues about how to explain drug problems or indeed technical
      issues about the best possible treatment for such problems, but also social
      issues about how drug problems and drug treatment affected and were affected by
      social change. The paper uses an analytical framework in which drugs are co
      constructed with their social worlds. It uses this framework to investigate how
      conflicts emerged about the different ways of conceiving of the relationship
      between methadone and Danish society. METHODS: Documentary data from the archives
      of a pressure group of parents of children with drug problems, the archives of an
      addiction doctor, newspaper articles, and policy documents from that time were
      coded in order to identify and analyze central controversies. RESULTS: The
      methadone controversy of the 1970s was not just about the best treatment methods,
      but also a matter of the future of the Danish welfare state. The nation debated
      whether it should medicalise a social problem or solve it through social reform.
      CONCLUSION: Drug treatment is not just a technical issue, but also a political
      issue and this needs to be accounted for when making drug policy.

PMID- 24120442
TI  - Crack across the Americas - a massive problem in continued search of viable
      answers: exemplary views from the North (Canada) and the South (Brazil).

PMID- 24120443
TI  - Source-based morphometry reveals distinct patterns of aberrant brain volume in
      delusional infestation.
AB  - Little is known about the neural correlates of delusional infestation (DI), the
      delusional belief to be infested with pathogens. So far, evidence comes mainly
      from case reports and case series. We investigated brain morphology in 16 DI
      patients and 16 healthy controls using structural magnetic resonance imaging and
      a multivariate data analysis technique, i.e. source-based morphometry (SBM). In
      addition, we explored differences in brain structure in patient subgroups based
      on disease aetiology. SBM revealed two patterns exhibiting significantly (p<0.05,
      Bonferroni-corrected) lower grey and higher white matter volume in DI patients
      compared to controls. Lower grey matter volume was found in medial prefrontal
      cortex, anterior cingulate cortex, medial temporal lobe structures
      (parahippocampus and hippocampus), sensorimotor cortices, bilateral insula and
      thalamus and inferior parietal regions. Higher white matter volume was found in
      medial and middle frontal and temporal cortices, left insula and lentiform
      nucleus. Grey matter volume was abnormal in both "psychiatric" (primary DI and DI
      associated with an affective disorder) and "organic" DI (DI due to a medical
      condition). In contrast, aberrant white matter volume was only confirmed for the
      "organic" DI patient subgroup. These results suggest prefrontal, temporal,
      parietal, insular, thalamic and striatal dysfunction underlying DI. Moreover, the
      data suggest that aetiologically distinct presentations of DI share similar
      patterns of abnormal grey matter volume, whereas aberrant white matter volume
      appears to be restricted to organic cases. 

PMID- 24120444
TI  - Crithidia fasciculata adenosine transporter 1 (CfAT1), a novel high-affinity
      equilibrative nucleoside transporter specific for adenosine.
AB  - Most eukaryotic organisms including protozoans like Crithidia, Leishmania, and
      Plasmodium encode a repertoire of equilibrative nucleoside transporters (ENTs).
      Using genomic sequencing data from Crithidia fasciculata, we discovered that this
      organism contains multiple ENT genes of highly similar sequence to the previously
      cloned and characterized adenosine transporter CfNT1: CfAT1 and CfNT3, and an
      allele of CfAT1, named CfAT1.2. Characterization of CfAT1 shows that it is an
      adenosine-only transporter, 87% identical to CfNT1 in protein sequence, with a 50
      fold lower Km for adenosine. Site directed mutation of a key residue in
      transmembrane domain 4 (TM4) in both CfNT1 and CfAT1 shows that lysine at this
      position results in a high affinity phenotype, while threonine decreases
      adenosine affinity in both transporters. These results show that C. fasciculata
      has at least two adenosine transporters, and that as in other protozoan ENTs, a
      lysine residue in TM4 plays a key role in ligand affinity. 

PMID- 24120446
TI  - Enrichment of phosphatidylinositols with specific acyl chains.
AB  - There are six major species of phospholipids in eukaryotes, each of which plays
      unique structural and functional roles. One species, phosphatidylinositol (PI)
      only contributes about 2-10% of the total phospholipid pool. However, they are
      critical factors in the regulation of several fundamental processes such as in
      membrane dynamics and signal transduction pathways. Although numerous acyl
      species exist, PI species are enriched with one specific acyl chain composition
      at both sn-1 and sn-2 positions. Recent work has identified several enzymes that
      act on lipids to lead to the formation or interconversion of PI species that
      exhibit acyl chain specificity. These enzymes contribute to this lipid's
      enrichment with specific acyl chains. The nature of the acyl chains on signaling
      lipids has been shown to contribute to their specificity. Here we review some of
      the critical functions of PI and the multiple pathways in which PI can be
      produced and metabolized. We also discuss a common motif that may confer
      arachidonoyl specificity to several of the enzymes involved. This article is part
      of a Special Issue entitled: Membrane Structure and Function: Relevance in the
      Cell's Physiology, Pathology and Therapy. 

PMID- 24120445
TI  - Increased concentrations of C-reactive protein but not high-mobility group box 1
      in dogs with naturally occurring sepsis.
AB  - Sepsis is difficult to diagnose and remains a common mortality cause worldwide in
      both humans and animals. The uterine infection pyometra causes sepsis in more
      than half of affected dogs and therefore allows the natural physiological
      development of sepsis to be studied. To find a sepsis-specific biochemical marker
      that could be combined with conventional clinical criteria for a more robust and
      quick diagnosis of sepsis, we measured systemic concentrations of high-mobility
      group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74%
      of which had sepsis. We also measured concentrations of the major acute phase
      protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin
      F2alpha metabolite (PGM) to assess the relative contribution of HMGB1 to the
      detection of systemic inflammation and endotoxaemia. We found that HMGB1
      concentrations, in line with concentrations of CRP and PGM, were significantly
      increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1,
      were significantly higher in dogs with sepsis compared to dogs without sepsis.
      Although serum HMGB1 did not differ between dogs with or without sepsis and was
      not correlated with either CRP or PGM concentrations, HMGB1 was correlated with
      the total white blood cell counts, suggesting an independent regulation and
      involvement in inflammation. 

PMID- 24120447
TI  - Importance of polarity of the alpha4-alpha5 loop residue-Asn(166) in the pore
      forming domain of the Bacillus thuringiensis Cry4Ba toxin: implications for ion
      permeation and pore opening.
AB  - Bacillus thuringiensis Cry4Ba toxin is lethal to mosquito-larvae by forming ion
      permeable pores in the target midgut cell membrane. Previously, the polarity of
      Asn(166) located within the alpha4-alpha5 loop composing the Cry4Ba pore-forming
      domain was shown to be crucial for larvicidal activity. Here, structurally stable
      mutant toxins of both larvicidal-active (N166D) and inactive (N166A and N166I)
      mutants were FPLC-purified and characterized for their relative activities in
      liposomal-membrane permeation and single-channel formation. Similar to the 65-kDa
      trypsin-activated wild-type toxin, the N166D bio-active mutant toxin was still
      capable of releasing entrapped calcein from lipid vesicles. Conversely, the two
      other bio-inactive mutants showed a dramatic decrease in causing membrane
      permeation. When the N166D mutant was incorporated into planar lipid bilayers
      (under symmetrical conditions at 150mM KCl, pH8.5), it produced single-channel
      currents with a maximum conductance of about 425pS comparable to the wild-type
      toxin. However, maximum conductances for single K(+)-channels formed by both bio
      inactive mutants (N166I and N166A) were reduced to approximately 165-205pS.
      Structural dynamics of 60-ns simulations of a trimeric alpha4-alpha5 pore model
      in a fully hydrated-DMPC system revealed that an open-pore structure could be
      observed only for the simulated pores of the wild type and N166D. Additionally,
      the number of lipid molecules interacting with both wild-type and N166D pores is
      relatively higher than those of N166A and N166I pores. Altogether, our results
      further signify that the polarity at the alpha4-alpha5 loop residue-Asn(166) is
      directly involved in ion permeation through the Cry4Ba toxin-induced ionic pore
      and pore opening at the membrane-water interface. 

PMID- 24120448
TI  - A molecular and morphological exploration of the generic boundaries in the family
      Melithaeidae (Coelenterata: Octocorallia) and its taxonomic consequences.
AB  - The validity of the currently recognized melithaeid genera (Acabaria, Clathraria,
      Melithaea, Mopsella, Wrightella) with the exception of the recently added genus
      Asperaxis, has puzzled scientists for almost a century. Diagnostic morphological
      characters are often missing or are obscured by the variation in sclerite forms.
      Consequently, species are difficult to assign to genera. In this study the
      current genera and their taxonomic positions are reviewed and reassessed based on
      material collected from the Indo-Pacific, Red Sea and Indian Ocean as far south
      as South Africa. Molecular data were obtained for four different loci, both
      mitochondrial (COI, mtMutS, ND6) and nuclear (28S rDNA). Combining the molecular
      and morphological data revealed that all former genera, except for the monotypic
      genus Asperaxis and the genus Wrightella are paraphyletic. Molecular data for the
      two subfamilies (Asperaxinae and Melithaeinae) within the Melithaeidae, in
      comparison with the outgroup, indicated that the family is also paraphyletic.
      Furthermore we observed that species did not cluster according to their present
      morphological classification but instead clustered according to a biogeographical
      pattern. Species from the Red Sea, Indian Ocean and Central Pacific,
      respectively, grouped into well supported clades. Consequently, we did not find
      morphological- or phylogenetic support to maintain the generic names Acabaria,
      Clathraria, Mopsella and Wrightella. Therefore these names are synonymised with
      the oldest available generic name, Melithaea. As a result, five secondary
      homonyms originated; these junior homonyms are herein renamed, viz. Melithaea
      hendersoni nom. nov, Melithaea mcqueeni nom. nov., Melithaea shanni nom. nov.,
      Melithaea thorpeae nom. nov., and Melithaea wrighti nom. nov. Additionally,
      neotypes are selected for Melithaea ochracea to stabilize the genus Melithaea,
      and for Acabaria rubra. 

PMID- 24120449
TI  - The first molecular phylogeny of Chilodontidae (Teleostei: Ostariophysi:
      Characiformes) reveals cryptic biodiversity and taxonomic uncertainty.
AB  - Chilodontidae is a small family of eight described characiform species popularly
      known as headstanders. These small to moderately sized fishes are well known to
      aquarists, who prize their striking spotted pigmentation and unusual behaviors,
      and to systematists, who have revised both chilodontid genera in recent memory
      and studied their phylogenetic relationships using a comprehensive morphological
      dataset. However, no molecular phylogeny for the family has ever been proposed.
      Here, we reconstruct phylogenetic relationships for all eight known chilodontid
      species using three mitochondrial and two nuclear loci. Results largely agree
      with the previous morphological hypothesis, and confirm the monophyly of the
      family as well as its included genera, Caenotropus and Chilodus. The molecular
      topology differs slightly from the morphological hypothesis by placing
      Caenotropus maculosus rather than C. mestomorgmatos as the sister to the
      remaining three congeners, and by reconstructing the Curimatidae as the closest
      outgroup family, rather than the Anostomidae. However, the topologies supported
      by the morphological data were only slightly less likely and could not be
      rejected via Shimodaira-Hasegawa tests. Within Chilodus, two described species
      with distinctive pigmentation (C. fritillus and C. zunevei) appear embedded
      within the broad distributed C. punctatus clade, suggesting the presence of
      cryptic taxa with polymorphic pigmentation within the present concept of C.
      punctatus. Future work should combine morphological and molecular data to revisit
      the taxonomy and systematics of Chilodus and determine species limits within the
      C. punctatus-group sensu lato. 

PMID- 24120450
TI  - Analysis of gene expression in canine idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) in dogs is a rare disease of unknown
      aetiology, seen in terrier breeds, particularly the West Highland white terrier
      (WHWT). The aim of this study was to determine pulmonary gene expression in
      canine IPF in order to gain insights into the pathogenesis of the disease and to
      identify possible biomarkers. Microarray analyses were conducted to determine
      gene expression profiles in the lungs of dogs with IPF and control dogs of
      various breeds. More than 700 genes were identified as having greater than two
      fold difference in expression between the two groups. The significant biological
      functions associated with these genes were related to cellular growth and
      proliferation, developmental processes, cellular movement, cell to cell
      signalling and interaction, and antigen presentation. Altered levels of
      expression were confirmed by quantitative reverse transcriptase PCR for genes
      encoding chemokine (C-C) ligand (CCL) 2 (+4.9 times), CCL7 (+6.8 times),
      interleukin 8 (+4.32 times), chemokine (C-X-C) ligand 14 (+3.4 times), fibroblast
      activation protein (+4.7 times) and the palate, lung and nasal associated protein
      (PLUNC, -25 times). Serum CCL2 concentrations were significantly higher in WHWTs
      with IPF (mean 628.1 pg/mL, interquartile range 460.3-652.7 pg/mL) than
      unaffected WHWTs (mean 344.0 pg/mL, interquartile range 254.5-415.5 pg/mL;
      P=0.001). The results support CCL2 as a candidate biomarker for IPF in dogs.

PMID- 24120451
TI  - Equine pastern vasculitis: a clinical and histopathological study.
AB  - Equine pastern vasculitis is clinically challenging and the underlying
      aetiopathogenesis is unclear. The aims of this retrospective study were to
      establish histopathological criteria for pastern vasculitis, to look for an
      underlying cause, to investigate whether the histopathological lesions are
      associated with a distinct clinical picture, to assess if and how the clinical
      picture varies, and to determine the treatment response. Skin biopsies and
      clinical data from 20 horses with a diagnosis of vasculitis of the distal
      extremities were investigated and histology was compared to biopsies from healthy
      horses. It was concluded that intramural inflammatory cells, leukocytoclasia with
      nuclear dust, thickening and oedema of the vessel walls, and microhaemorrhages
      are highly specific histological findings in equine pastern vasculitis. Based on
      the feedback from the clinicians, the lesions were mostly seen on the lateral and
      medial aspects of un-pigmented legs. Lesions in white skin were characterised by
      exudation and crusts, whereas those in pigmented skin were alopecic and
      characterised by scaling. The response to treatment was poor and the prognosis
      guarded. No association was found between any of the histopathological findings
      and a distinct clinical picture. An underlying cause of equine pastern vasculitis
      could not be identified. Considering the large number of confounding factors, the
      causative agents are difficult to identify, but may involve drugs or a
      hypersensitivity reactions to yet unknown antigens. 

PMID- 24120452
TI  - Strain-specific variation in a soilborne phytopathogenic fungus for the
      expression of genes involved in pH signal transduction pathway, pathogenesis and
      saprophytic survival in response to environmental pH changes.
AB  - The soilborne fungus Gaeumannomyces graminis var. tritici (Ggt) causes take-all,
      a wheat root disease. In an original strain-specific way, a previous study
      indicates that inside the Ggt species, some strains grow preferentially at acidic
      pH and other strains at neutral/alkaline pH. The most important mechanism for a
      fungal response to the environmental pH is the Pal pathway which integrates the
      products of the six pal genes and the transcription factor PacC. To evaluate
      whether the Ggt strain-specific growth in function of the ambient pH is mediated
      via the Pal pathway, a transcriptional study of the genes encoding this pathway
      was carried out. This study provided the first evidence that the pH signalling
      pathway similar to those described in other fungi operated in Ggt. The pacC gene
      was induced at neutral pH whatever the strain. In an original way, the expression
      of Ggt genes coding for the different Pal proteins depended on the strain and on
      the ambient pH. In the strain growing better at acidic pH, few pal genes were pH
      regulated, and some were overexpressed at neutral pH when regulated. In the
      strain growing better at neutral pH, underexpression of most of the pal genes at
      neutral pH occurred. The strains displayed higher gene expression in the ambient
      pH that unfavoured their growth as if it was a compensation system. All pH taken
      together, a globally weaker Pal transcript level occurred in the strains that
      were less sensitive to acidic pH, and on the contrary, the strain growing better
      on neutral pH showed higher Pal mRNA levels. The expression of genes involved in
      pathogenesis and saprophytic growth was also regulated by the ambient pH and the
      strain: each gene displayed a specific pH-regulation that was similar between
      strains. But all pH taken together, the global transcript levels of four out of
      six genes were higher in the strain growing better on neutral pH. Altogether, for
      the first time, the results show that inside a species, conditions affecting
      environmental pH modulate the expression of genes in an original strain-specific
      way. 

PMID- 24120454
TI  - Integrating clinical decision support to increase HIV and chlamydia screening.

PMID- 24120453
TI  - Phosphatidic acid and phosphoinositides facilitate liposome association of Yas3p
      and potentiate derepression of ARE1 (alkane-responsive element one)-mediated
      transcription control.
AB  - In the n-alkane assimilating yeast Yarrowia lipolytica, the expression of ALK1,
      encoding a cytochrome P450 that catalyzes terminal mono-oxygenation of n-alkanes,
      is induced by n-alkanes. The transcription of ALK1 is regulated by a
      heterocomplex that comprises the basic helix-loop-helix transcription activators,
      Yas1p and Yas2p, and binds to alkane-responsive element 1 (ARE1) in the ALK1
      promoter. An Opi1 family transcription repressor, Yas3p, represses transcription
      by binding to Yas2p. Yas3p localizes in the nucleus when Y. lipolytica is grown
      on glucose but localizes to the endoplasmic reticulum (ER) upon the addition of n
      alkanes. In this study, we showed that recombinant Yas3p binds to the acidic
      phospholipids, phosphatidic acid (PA) and phosphoinositides (PIPs), in vitro. The
      ARE1-mediated transcription was enhanced in vivo in mutants defective in an
      ortholog of the Saccharomyces cerevisiae gene PAH1, encoding PA phosphatase, and
      in an ortholog of SAC1, encoding PIP phosphatase in the ER. Truncation mutation
      analyses for Yas3p revealed two regions that bound to PA and PIPs. These results
      suggest that the interaction with acidic phospholipids is important for the n
      alkane-induced association of Yas3p with the ER membrane. 

PMID- 24120455
TI  - Effect of permeation enhancers on dynamic mechanical properties of acrylate
      pressure sensitive adhesives.
AB  - Physico-chemical properties of permeation enhancers like molecular weight/size,
      hydrophobicity/hydrophilicity, co-solvency, etc. are necessary during their
      selection for pharmaceutical product development. Chemical permeation enhancers
      modulate the viscoelastic properties of pressure sensitive adhesives. The extent
      of this modulation depends upon the molecular size and branching of the polymeric
      chains. The functional nature of this branching additionally changes the peel and
      tack properties of PSA's. Chemical permeation enhancers alone are not able to
      modify viscoelastic properties of aqueous based PSA's as compared with their
      solvent based counterparts. These modulated mechanical aspects need to be
      maintained throughout development of transdermal patch along with other
      pharmaceutical aspects like drug release and drug stability. 

PMID- 24120456
TI  - Constitutive mosaic aneuploidy is a unique genetic feature widespread in the
      Leishmania genus.
AB  - Using fluorescence in situ hybridization, we determined the ploidy of four
      species of Leishmania: Leishmania infantum, Leishmania donovani, Leishmania
      tropica and Leishmania amazonensis. We found that each cell in a strain possesses
      a combination of mono-, di- and trisomies for all chromosomes; ploidy patterns
      were different among all strains/species. These results extend those we
      previously described in Leishmania major, demonstrating that mosaic aneuploidy is
      a genetic feature widespread to the Leishmania genus. In addition to the genetic
      consequences induced by this mosaicism, the apparent absence of alternation
      between haploid/diploid stages questions the modality of genetic exchange in
      Leishmania sp. 

PMID- 24120458
TI  - Nitrogen evolution during the co-combustion of hydrothermally treated municipal
      solid waste and coal in a bubbling fluidized bed.
AB  - Nitrogen evolution was studied during the co-combustion of hydrothermally treated
      municipal solid wastes (HT MSW) and coal in a bubbling fluidized bed (BFB). HT
      MSW blending ratios as 10%, 20% and 30% (wt.%) were selected and tested at 700,
      800, 900  degrees C. Emissions of NO and N2O from blends were measured and
      compared with the results of mono-combustion trials. Moreover, concentrations of
      precursors like NH3 and HCN were also quantified. The results are summarized as
      follows: NO emissions were predominant in all the cases, which rose with
      increasing temperature. The blending of HT MSW contributed to the NO reduction.
      N2O emissions decreased with temperature rising and the blending of HT MSW also
      presented positive effects. At 30% HT MSW addition, both NO and N2O emissions
      showed the lowest values (391.85 ppm and 55.33 ppm, respectively at 900  degrees
      C). For the precursors, more HCN was detected than NH3 and both played important
      roles on the gas side nitrogen evolution.

PMID- 24120457
TI  - Investigations of TB vaccine-induced mucosal protection in mice.
AB  - A better understanding of mucosal immunity is required to develop more protective
      vaccines against Mycobacterium tuberculosis. We developed a murine aerosol
      challenge model to investigate responses capable of protecting against mucosal
      infection. Mice received vaccinations intranasally with CpG-adjuvanted antigen
      85B (Ag85B/CpG) and/or Bacillus Calmette-Guerin (BCG). Protection against aerosol
      challenge with a recombinant GFP-expressing BCG was assessed. Mucosal prime/boost
      vaccinations with Ag85B/CpG and BCG were protective, but did not prevent lung
      infection indicating more efficacious mucosal vaccines are needed. Our novel
      finding that protection correlated with increased airway dendritic cells early
      post-challenge could help guide the development of enhanced mucosal vaccines. 

PMID- 24120459
TI  - Pilot scale evaluation of the BABIU process--upgrading of landfill gas or biogas
      with the use of MSWI bottom ash.
AB  - Biogas or landfill gas can be converted to a high-grade gas rich in methane with
      the use of municipal solid waste incineration bottom ash as a reactant for
      fixation of CO2 and H2S. In order to verify results previously obtained at a
      laboratory scale with 65-90 kg of bottom ash (BA), several test runs were
      performed at a pilot scale, using 500-1000 kg of bottom ash and up to 9.2 Nm(3)/h
      real landfill gas from a landfill in the Tuscany region (Italy). The input flow
      rate was altered. The best process performance was observed at a input flow rate
      of 3.7 Nm(3)/(htBA). At this flow rate, the removal efficiencies for H2S were
      approximately 99.5-99%.

PMID- 24120460
TI  - A multilevel structural equation modeling analysis of vulnerabilities and
      resilience resources influencing affective adaptation to chronic pain.
AB  - The processes of individual adaptation to chronic pain are complex and occur
      across multiple domains. We examined the social, cognitive, and affective context
      of daily pain adaptation in individuals with fibromyalgia and osteoarthritis. By
      using a sample of 260 women with fibromyalgia or osteoarthritis, we examined the
      contributions of pain catastrophizing, negative interpersonal events, and
      positive interpersonal events to daily negative and positive affect across 30days
      of daily diary data. Individual differences and daily fluctuations in predictor
      variables were estimated simultaneously by utilizing multilevel structural
      equation modeling techniques. The relationships between pain and negative and
      positive affect were mediated by stable and day-to-day levels of pain
      catastrophizing as well as day-to-day positive interpersonal events, but not
      negative interpersonal events. There were significant and independent
      contributions of pain catastrophizing and positive interpersonal events to
      adaptation to pain and pain-related affective dysregulation. These effects occur
      both between persons and within a person's everyday life. 

PMID- 24120461
TI  - Cancer pain is not necessarily correlated with spinal overexpression of reactive
      glia markers.
AB  - Bone cancer pain is a common and disruptive symptom in cancer patients. In cancer
      pain animal models, massive reactive astrogliosis in the dorsal horn of the
      spinal cord has been reported. Because astrocytes may behave as driving partners
      for pathological pain, we investigated the temporal development of pain behavior
      and reactive astrogliosis in a rat bone cancer pain model induced by injecting
      MRMT-1 rat mammary gland carcinoma cells into the tibia. Along with the
      development of bone lesions, a gradual mechanical and thermal allodynia and
      hyperalgesia as well as a reduced use of the affected limb developed in bone
      cancer-bearing animals, but not in sham-treated animals. Dorsal horn Fos
      expression after nonpainful palpation of the injected limb was also increased in
      bone cancer-bearing animals. However, at any time during the evolution of tumor,
      there was no increase in glial fibrillary acidic protein (GFAP) immunoreactivity
      in the dorsal horn. Further analysis at 21days after injection of the tumor
      showed no increase in GFAP and interleukin (IL) 1beta transcripts, number of
      superficial dorsal horn S100beta protein immunoreactive astrocytes, or
      immunoreactivity for microglial markers (OX-42 and Iba-1). In contrast, all these
      parameters were increased in the dorsal horn of rats 2weeks after sciatic nerve
      ligation. This suggests that in some cases, bone cancer pain may not be
      correlated with spinal overexpression of reactive glia markers, whereas
      neuropathic pain is. Glia may thus play different roles in the development and
      maintenance of chronic pain in these 2 situations. 

PMID- 24120462
TI  - 1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex
      regional pain syndrome-related dystonia.
AB  - In complex regional pain syndrome (CRPS)-related dystonia, compelling evidence
      points to the involvement of the central nervous system, but the underpinning
      pathobiology is still unclear. Thus, to enable a hypothesis-free, unbiased view
      of the problem and to obtain new insight into the pathobiology of dystonia in
      CRPS, we applied an exploratory metabolomics analysis of cerebrospinal fluid
      (CSF) of patients with CRPS-related dystonia. (1)H-NMR spectroscopy in
      combination with multivariate modeling were used to investigate metabolic
      profiles of a total of 105 CSF samples collected from patients with CRPS-related
      dystonia and controls. We found a significantly different metabolic profile of
      CSF in CRPS patients compared to controls. The differences were already reflected
      in the first two principal components of the principal component analysis model,
      which is an indication that the variance associated with CRPS is stronger than
      variance caused by such classical confounders as gender, age, or individual
      differences. A supervised analysis generated a strong model pinpointing the most
      important metabolites contributed to the metabolic signature of patients with
      CRPS-related dystonia. From the set of identified discriminators, the most
      relevant metabolites were 2-keto-isovalerate, glucose, glutamine, and lactate,
      which all showed increased concentrations, and urea, which showed decreased
      concentration in CRPS subjects. Our findings point at a catabolic state in
      chronic CRPS patients with dystonia that is likely associated with inflammation. 

PMID- 24120463
TI  - Call for more international collaboration in metastatic seminoma.

PMID- 24120464
TI  - The prognostic importance of metastatic site in men with metastatic castration
      resistant prostate cancer.
AB  - The presence of visceral metastases is adversely prognostic in men with
      metastatic castration-resistant prostate cancer (mCRPC), but the prognostic
      impact of the site of visceral metastasis is unclear. Men with mCRPC in the TAX
      327 phase 3 trial receiving docetaxel or mitoxantrone every 3 wk or weekly
      docetaxel, each with prednisone, were analyzed retrospectively to study the
      impact of the site of visceral metastasis on overall survival (OS). Patients were
      assessed for OS by site of metastases: liver with or without other sites, lung
      with or without bone or lymph nodes, bone plus lymph nodes, bone only, and lymph
      nodes only. Cox proportional hazards regression, adjusted for treatment and
      stratification factors, was performed. Men with liver metastases with or without
      other metastases had shorter median OS (10.0 mo; 95% confidence interval [CI],
      5.4-11.5) than men with lung metastases with or without bone or nodal metastases
      (median OS: 14.4 mo; 95% CI, 11.5-22.4). Men with lymph node-only disease had the
      best median OS (26.7 mo; 95% CI, 22.3-34.2), followed by men with bone-only
      metastases (median OS: 19.0 mo; 95% CI, 18.2-20.7) and bone-plus-node disease
      (median OS: 15.7 mo; 95% CI, 14.4-17.2). Thus, pattern of spread including site
      of visceral metastasis confers a differential prognostic impact. These data
      require validation and may inform trial design and therapy. 

PMID- 24120465
TI  - Systemic G-CSF attenuates cerebral inflammation and hypomyelination but does not
      reduce seizure burden in preterm sheep exposed to global hypoxia-ischemia.
AB  - Hypoxic-ischemic encephalopathy (HIE) is common in preterm infants, but currently
      no curative therapy is available. Cell-based therapy has a great potential in the
      treatment of hypoxic-ischemic preterm brain injury. Granulocyte-colony
      stimulating factor (G-CSF) is known to mobilize endogenous hematopoietic stem
      cells (HSC) and promotes proliferation of endogenous neural stem cells. On these
      grounds, we hypothesized that systemic G-CSF would be neuroprotective in a large
      translational animal model of hypoxic-ischemic injury in the preterm brain.
      Global hypoxia-ischemia (HI) was induced by transient umbilical cord occlusion in
      instrumented preterm sheep. G-CSF treatment (100MUg/kg intravenously, during five
      consecutive days) was started one day before the global HI insult to ascertain
      mobilization of endogenous stem cells within the acute phase after global HI.
      Mobilization of HSC and neutrophils was studied by flow cytometry. Brain sections
      were stained for microglia (IBA-1), myelin basic protein (MBP) and
      myeloperoxidase (MPO) to study microglial proliferation, white matter injury and
      neutrophil invasion respectively. Electrographic seizure activity was analyzed
      using amplitude-integrated electroencephalogram (aEEG). G-CSF effectively
      mobilized CD34-positive HSC in the preterm sheep. In addition, G-CSF caused
      marked mobilization of neutrophils, but did not influence enhanced invasion of
      neutrophils into the preterm brain after global HI. Microglial proliferation and
      hypomyelination following global HI were reduced as a result of G-CSF treatment.
      G-CSF did not cause a reduction of the electrographic seizure activity after
      global HI. In conclusion, G-CSF induced mobilization of endogenous stem cells
      which was associated with modulation of the cerebral inflammatory response and
      reduced white matter injury in an ovine model of preterm brain injury after
      global HI. G-CSF treatment did not improve neuronal function as shown by seizure
      analysis. Our study shows that G-CSF treatment has neuroprotective potential
      following hypoxic-ischemic injury in the preterm brain. 

PMID- 24120466
TI  - Altered astrocytic expression of TDP-43 does not influence motor neuron survival.
AB  - The role of glia as a contributing factor to motor neuron (MN) death in
      amyotrophic lateral sclerosis (ALS) is becoming increasingly appreciated.
      However, most studies implicating astrocytes have focused solely on models of ALS
      caused by superoxide dismutase 1 (SOD1) mutations. The goal of our study was to
      determine whether astrocytes contribute to wild-type MN death in the case of ALS
      caused by mutations in tar-DNA binding protein 43 (TDP-43). Since it is currently
      unknown how TDP-43 mutations cause disease, we derived astrocytes for study from
      both gain and loss of function mouse models of TDP-43. Astrocytes overexpressing
      mutant TDP-43(A315T) as well as astrocytes lacking TDP-43 were morphologically
      indistinguishable from wild-type astrocytes in vitro. Furthermore, astrocytes
      with these TDP-43 alterations did not cause the death of wild-type MNs in co
      culture. To investigate the in vivo effects of TDP-43 alterations in astrocytes,
      glial-restricted precursors were transplanted to the wild-type rat spinal cord
      where they differentiated into astrocytes and interacted with host MNs.
      Astrocytes with TDP-43 alterations did not cause host wild-type MN damage
      although they were capable of engrafting and interacting with host MNs with the
      same efficiency as wild-type astrocytes. These data indicate that astrocytes do
      not adopt the same toxic phenotype as mutant SOD1 astrocytes when TDP-43 is
      mutated or expression levels are modified. Our study reinforces the heterogeneity
      in ALS disease mechanisms and highlights the potential for future screening
      subsets of ALS patients prior to treatment with cell type-directed therapies. 

PMID- 24120467
TI  - Rapid maturation of voice and linguistic processing systems in preschool
      children: a near-infrared spectroscopic study.
AB  - To better understand how voice and linguistic processing systems develop during
      the preschool years, changes in cerebral oxygenation were measured bilaterally
      from temporal areas using multi-channel near-infrared spectroscopy (NIRS). NIRS
      was recorded while children listened to their mothers' voice (MV), an unfamiliar
      female voice (UV) and environmental sound (ES) stimuli. Twenty typical children
      (aged 3-6years) were divided into younger (Y) (n=10, male=5; aged 3-4.5years) and
      older (O) (n=10, male=5; aged 4.5-6years) groups. In the Y group, while MV
      stimuli significantly activated anterior temporal areas with a right predominance
      compared to ES stimuli, they significantly activated left mid-temporal areas
      compared to UV stimuli. These temporal activations were significantly higher in
      the Y group compared to the O group. Furthermore, only the O group exhibited
      significant habituation and gender differences in the left mid-temporal area
      during MV perception. These findings suggest that the right voice-related and the
      left language-related temporal areas already exist in the Y group, and that MV
      stimuli modulate these areas differently in the two age groups. Therefore, we
      conclude that a mother's voice plays an important role in the maturation of the
      voice and linguistic processing systems, particularly during the first half of
      the preschool-aged period. This role may decrease during the latter half of the
      preschool-aged period due to rapid development of these systems as children age. 

PMID- 24120468
TI  - Transcatheter aortic valve implantation in a very young patient.
AB  - Transcatheter aortic valve implantation (TAVI) is the standard treatment for
      patients with severe aortic stenosis and unacceptable surgical risk. These are
      usually elderly patients with multiple comorbidities. We report the case of a 20
      year-old man with mandibuloacral dysplasia, an extremely rare premature ageing
      syndrome, and severe symptomatic aortic stenosis, referred to our center for TAVI
      after being considered unsuitable for surgical aortic valve replacement. TAVI by
      a transfemoral approach was performed successfully. Severe acute respiratory
      failure that did not respond to optimal conventional treatment led us to employ
      venovenous extracorporeal membrane oxygenation. The device was removed after 10
      days, and the patient was discharged home 27 days later. At one-year follow-up he
      is in NYHA class I with full functional autonomy. To the best of our knowledge,
      this is the youngest patient to undergo TAVI reported in the literature. 

PMID- 24120469
TI  - Myocardial remote ischemic preconditioning: from pathophysiology to clinical
      application.
AB  - Short periods of myocardial ischemia followed by reperfusion induce a
      cardioprotective mechanism when the myocardium is subsequently subjected to a
      prolonged period of ischemia, a phenomenon known as ischemic preconditioning. As
      well as its application in the myocardium, ischemic preconditioning can also be
      induced by brief interruptions of blood flow to other organs, particularly
      skeletal muscle. Transient ischemia induced noninvasively by inflating a cuff on
      a limb, followed by reperfusion, helps reduce the damage caused to the myocardium
      by interruption of the coronary circulation. Remote ischemic preconditioning
      involves activation of humoral and/or neural pathways that open mitochondrial ATP
      sensitive potassium channels in the myocardium and close mitochondrial
      permeability transition pores, making cardiomyocytes less vulnerable to ischemia
      induced cell death. This cardioprotective mechanism is now being translated into
      clinical practice, with positive results in several clinical trials in coronary
      artery bypass surgery, surgical repair of abdominal aortic aneurysms, valve
      replacement surgery and percutaneous coronary intervention. However, certain
      factors weaken the subcellular mechanisms of preconditioning - age,
      comorbidities, medication, anesthetic protocol - and appear to explain the
      heterogeneity of results in some studies. Detailed understanding of the pathways
      involved in cardioprotection induced by ischemic preconditioning is expected to
      lead to the development of new drugs to reduce the consequences of prolonged
      ischemia. 

PMID- 24120470
TI  - Neuromedin B stimulates the hypothalamic-pituitary-gonadal axis in male rats.
AB  - Neuromedin B (NMB) is a highly conserved bombesin-related peptide found in
      mammals. NMB mRNA is detected in the central nervous system (CNS) and is highly
      expressed in the rat hypothalamus, in particular the medial preoptic area and the
      arcuate nucleus. The mammalian bombesin family of receptors consists of three
      closely related G protein coupled receptors, BB1, BB2 and BB3. The BB1 receptor
      subtype has the highest affinity for NMB. NMB has well documented roles in the
      regulation of the thyroid axis and the stress axis in rats. However, there is
      little available data regarding the role of NMB in the regulation of the
      hypothalamic-pituitary-gonadal (HPG) axis. It is known that the NMB receptor is
      expressed in immortalised gonadotrophin releasing hormone (GnRH) releasing GT1-7
      cells and murine forebrain GnRH neurons, and that anterior pituitary NMB
      immunoreactivity is altered by changes in the sex steroid environment. The
      objective of these studies was thus to further investigate the effects of NMB on
      the HPG axis. Intracerebroventricular (ICV) administration of NMB (10 nmol) to
      adult male rats significantly increased plasma luteinising hormone (LH) levels 30
      min after injection (plasma LH ng/ml; saline 0.69+/-0.07, 10 nmol NMB 1.33+/
      0.17, P<0.01). In vitro, NMB stimulated GnRH release from hypothalamic explants
      from male rats and from hypothalamic GT1-7 cells. NMB had no significant effect
      on LH release from anterior pituitary explants from male rats, or from pituitary
      LbetaT2 cells in vitro. These results suggest a previously unreported role for
      NMB in the stimulation of the HPG axis via hypothalamic GnRH. Further work is now
      required to determine the receptor mediating the effects of NMB on the
      reproductive axis and the physiological role of NMB in reproduction.

PMID- 24120471
TI  - Acute iron overload and oxidative stress in brain.
AB  - An in vivo model in rat was developed by intraperitoneally administration of Fe
      dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe
      levels, as well as the labile iron pool (LIP) concentration, in brain from rats
      subjected to Fe-overload were markedly increased over control values, 6h after Fe
      administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate
      (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio
      in brain was significantly higher in Fe-dextran group, in relation to values in
      control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive
      substances (TBARS) generation rate and lipid radical (LR) content detected by
      Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were
      similar to control values. However, values of nuclear factor-kappaB
      deoxyribonucleic acid (NFkappaB DNA) binding activity were significantly
      increased (30%) after 8h of Fe administration, and catalase (CAT) activity was
      significantly enhanced (62%) 21h after Fe administration. Significant
      enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and
      striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was
      significantly increased after 8h of Fe administration in cortex, hippocampus and
      striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain
      seems to lead to enhanced NF-kappaB DNA binding activity, which may contribute to
      limit oxygen reactive species-dependent damage by effects on the antioxidant
      enzyme CAT activity. Moreover, data shown here clearly indicate that even though
      Fe increased in several isolated brain areas, this parameter was more drastically
      enhanced in striatum than in cortex and hippocampus. However, comparison among
      the net increase in LR generation rate, in different brain areas, showed
      enhancements in cortex lipid peroxidation, without changes in striatum and
      hippocampus LR generation rate after 6h of Fe overload. This information has
      potential clinical relevance, as it could be the key to understand specific brain
      damage occurring in conditions of Fe overload. 

PMID- 24120472
TI  - Effect of zeranol on expression of apoptotic and cell cycle proteins in murine
      placentae.
AB  - Mycotoxins are chemicals produced by fungus and many of them are toxic to humans.
      Zeranol is a mycotoxin used to promote growth in cattle in North America; yet
      such a practice draws concern about the residual compound in meat in European
      countries. In the present study, the toxicity of zeranol was tested in a mouse
      model for reproduction. Pregnant ICR mice were given p.o. daily doses of zeranol
      at 0, 1, 10, 100mg/kg for 4 days (from E13.5 to E16.5). Increased rates of fetal
      resorption at late gestation (E17.5) and preterm birth (<E18.5) were observed in
      mice treated with zeranol. The apparent factors causing these perinatal
      conditions were subsequently investigated. Perturbation of cell death or
      proliferation-related proteins might deter the growth and maintenance of the
      placentae, and the subsequent fetal resorption and preterm birth. Placental
      tissue isolated from pregnant mice at E17.5 showed that the expressions of Cdk2
      and 4, Cyclin D1 and Bcl-xL were reduced in zeranol-treatment groups. The
      downregulations might signify growth or maintenance failure in the placentae.
      Furthermore, reduction in the signaling proteins Erk-1/2 in the placentae could
      trigger the decrease in the cell cycle/apoptosis proteins. In addition, relaxin
      is associated with preterm labor. An increase in placental Relaxin-1 expression
      could also contribute to early delivery in this study. Result of the current
      study suggested that exposure to zeranol might introduce adverse effect in
      pregnancy. 

PMID- 24120473
TI  - Autocrine VEGF signaling promotes proliferation of neoplastic Barrett's
      epithelial cells through a PLC-dependent pathway.
AB  - BACKGROUND & AIMS: Tumor cells express vascular endothelial growth factor (VEGF),
      which induces angiogenesis. VEGF also activates VEGF receptors (VEGFRs) on or
      within tumor cells to promote their proliferation in an autocrine fashion. We
      studied the mechanisms of autocrine VEGF signaling in Barrett's esophagus cells.
      METHODS: Using Barrett's epithelial cell lines, we measured VEGF and VEGFR
      messenger RNA and protein, and studied the effects of VEGF signaling on cell
      proliferation and VEGF secretion. We studied the effects of inhibiting factors in
      this pathway on levels of phosphorylated phospholipase Cgamma1 (PLCG1), protein
      kinase C, and extracellular signal-regulated kinases (ERK)1/2. We performed
      immunohistochemical analysis of phosphorylated VEGFR2 on esophageal
      adenocarcinoma tissues. We studied effects of sunitinib, a VEGFR2 inhibitor, on
      proliferation of neoplastic cells and growth of xenograft tumors in mice.
      RESULTS: Neoplastic and non-neoplastic Barrett's cells expressed VEGF and VEGFR2
      messenger RNA and protein, with higher levels in neoplastic cells. Incubation
      with recombinant human VEGF significantly increased secretion of VEGF protein and
      cell number; knockdown of PLCG1 markedly reduced the recombinant human VEGF
      stimulated increase in levels of phosphorylated PLCG1 and phosphorylated ERK1/2
      in neoplastic cells. Esophageal adenocarcinoma tissues showed immunostaining for
      phosphorylated VEGFR2. Sunitinib inhibited VEGF signaling in neoplastic cells and
      reduced weight and volume of xenograft tumors in mice. CONCLUSIONS: Neoplastic
      and non-neoplastic Barrett's epithelial cells have autocrine VEGF signaling. In
      neoplastic Barrett's cells, VEGF activation of VEGFR2 initiates a PLCG1-protein
      kinase C-ERK pathway that promotes proliferation and is self-sustaining (by
      causing more VEGF production). Strategies to reduce autocrine VEGF signaling (eg,
      with sunitinib) might be used to prevent or treat cancer in patients with
      Barrett's esophagus.

PMID- 24120474
TI  - Proper development of the outer longitudinal smooth muscle of the mouse pylorus
      requires Nkx2-5 and Gata3.
AB  - BACKGROUND & AIMS: Infantile hypertrophic pyloric stenosis is a common birth
      anomaly characterized by obstruction of the pyloric lumen. A genome-wide
      association study implicated NKX2-5, which encodes a transcription factor that is
      expressed in embryonic heart and pylorus, in the pathogenesis of infantile
      hypertrophic pyloric stenosis. However, the function of the NKX2-5 in pyloric
      smooth muscle development has not been examined directly. We investigated the
      pattern of Nkx2-5 during the course of murine pyloric sphincter development and
      examined coexpression of Nkx2-5 with Gata3 and Sox9-other transcription factors
      with pyloric-specific mesenchymal expression. We also assessed pyloric sphincter
      development in mice with disruption of Nkx2-5 or Gata3. METHODS: We used
      immunofluorescence analysis to compare levels of NKX2-5, GATA3, and SOX9 in
      different regions of smooth muscle cells. Pyloric development was assessed in
      mice with conditional or germline deletion of Nkx2-5 or Gata3, respectively.
      RESULTS: Gata3, Nkx2-5, and Sox9 are coexpressed in differentiating smooth muscle
      cells of a distinct fascicle of the pyloric outer longitudinal muscle. Expansion
      of this fascicle coincides with development of the pyloric sphincter. Disruption
      of Nkx2-5 or Gata3 causes severe hypoplasia of this fascicle and alters pyloric
      muscle shape. Although expression of Sox9 requires Nkx2-5 and Gata3, there is no
      apparent hierarchical relationship between Nkx2-5 and Gata3 during pyloric outer
      longitudinal muscle development. CONCLUSIONS: Nkx2-5 and Gata3 are independently
      required for the development of a pyloric outer longitudinal muscle fascicle,
      which is required for pyloric sphincter morphogenesis in mice. These data
      indicate that regulatory changes that alter Nkx2-5 or Gata3 expression could
      contribute to pathogenesis of infantile hypertrophic pyloric stenosis.

PMID- 24120475
TI  - Nuclear death receptor TRAIL-R2 inhibits maturation of let-7 and promotes
      proliferation of pancreatic and other tumor cells.
AB  - BACKGROUND & AIMS: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL
      R1) (TNFRSF10A) and TRAIL-R2 (TNFRSF10B) on the plasma membrane bind ligands that
      activate apoptotic and other signaling pathways. Cancer cells also might have
      TRAIL-R2 in the cytoplasm or nucleus, although little is known about its
      activities in these locations. We investigated the functions of nuclear TRAIL-R2
      in cancer cell lines. METHODS: Proteins that interact with TRAIL-R2 initially
      were identified in pancreatic cancer cells by immunoprecipitation, mass
      spectrometry, and immunofluorescence analyses. Findings were validated in colon,
      renal, lung, and breast cancer cells. Functions of TRAIL-R2 were determined from
      small interfering RNA knockdown, real-time polymerase chain reaction, Drosha
      activity, microRNA array, proliferation, differentiation, and immunoblot
      experiments. We assessed the effects of TRAIL-R2 overexpression or knockdown in
      human pancreatic ductal adenocarcinoma (PDAC) cells and their ability to form
      tumors in mice. We also analyzed levels of TRAIL-R2 in sections of PDACs and non
      neoplastic peritumoral ducts from patients. RESULTS: TRAIL-R2 was found to
      interact with the core microprocessor components Drosha and DGCR8 and the
      associated regulatory proteins p68, hnRNPA1, NF45, and NF90 in nuclei of PDAC and
      other tumor cells. Knockdown of TRAIL-R2 increased Drosha-mediated processing of
      the let-7 microRNA precursor primary let-7 (resulting in increased levels of
      mature let-7), reduced levels of the let-7 targets (LIN28B and HMGA2), and
      inhibited cell proliferation. PDAC tissues from patients had higher levels of
      nuclear TRAIL-R2 than non-neoplastic pancreatic tissue, which correlated with
      increased nuclear levels of HMGA2 and poor outcomes. Knockdown of TRAIL-R2 in
      PDAC cells slowed their growth as orthotopic tumors in mice. Reduced nuclear
      levels of TRAIL-R2 in cultured pancreatic epithelial cells promoted their
      differentiation. CONCLUSIONS: Nuclear TRAIL-R2 inhibits maturation of the
      microRNA let-7 in pancreatic cancer cell lines and increases their proliferation.
      Pancreatic tumor samples have increased levels of nuclear TRAIL-R2, which
      correlate with poor outcome of patients. These findings indicate that in the
      nucleus, death receptors can function as tumor promoters and might be therapeutic
      targets.

PMID- 24120476
TI  - MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote
      pancreatic tumor growth and progression.
AB  - BACKGROUND & AIMS: There has not been a broad analysis of the combined effects of
      altered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma
      (PDAC) cells, and it is unclear how these might affect tumor progression or
      patient outcomes. METHODS: We combined data from miRNA and messenger RNA (mRNA)
      expression profiles and bioinformatic analyses to identify an miRNA-mRNA
      regulatory network in PDAC cell lines (PANC-1 and MIA PaCa-2) and in PDAC samples
      from patients. We used this information to identify miRNAs that contribute most
      to tumorigenesis. RESULTS: We identified 3 miRNAs (MIR21, MIR23A, and MIR27A)
      that acted as cooperative repressors of a network of tumor suppressor genes that
      included PDCD4, BTG2, and NEDD4L. Inhibition of MIR21, MIR23A, and MIR27A had
      synergistic effects in reducing proliferation of PDAC cells in culture and growth
      of xenograft tumors in mice. The level of inhibition was greater than that of
      inhibition of MIR21 alone. In 91 PDAC samples from patients, high levels of a
      combination of MIR21, MIR23A, and MIR27A were associated with shorter survival
      times after surgical resection. CONCLUSIONS: In an integrated data analysis, we
      identified functional miRNA-mRNA interactions that contribute to growth of PDACs.
      These findings indicate that miRNAs act together to promote tumor progression;
      therapeutic strategies might require inhibition of several miRNAs.

PMID- 24120478
TI  - Phylogenetic estimates of speciation and extinction rates for testing ecological
      and evolutionary hypotheses.
AB  - Phylogenies are used to estimate rates of speciation and extinction, reconstruct
      historical diversification scenarios, and link these to ecological and
      evolutionary factors, such as climate or organismal traits. Recent models can now
      estimate the effects of binary, multistate, continuous, and biogeographic
      characters on diversification rates. Others test for diversity dependence (DD) in
      speciation and extinction, which has become recognized as an important process in
      numerous clades. A third class incorporates flexible time-dependent functions,
      enabling reconstruction of major periods of both expanding and contracting
      diversity. Although there are some potential problems (particularly for
      estimating extinction), these methods hold promise for answering many classic
      questions in ecology and evolution, such as the origin of adaptive radiations,
      and the latitudinal gradient in species richness. 

PMID- 24120477
TI  - Oral delivery of IL-27 recombinant bacteria attenuates immune colitis in mice.
AB  - BACKGROUND & AIMS: Treatment of inflammatory bowel disease would benefit from
      specific targeting of therapeutics to the intestine. We developed a strategy for
      localized delivery of the immunosuppressive cytokine interleukin (IL)-27, which
      is synthesized actively in situ by the food-grade bacterium Lactococcus lactis
      (LL-IL-27), and tested its ability to reduce colitis in mice. METHODS: The 2
      genes encoding mouse IL-27 were synthesized with optimal codon use for L lactis
      and joined with a linker; a signal sequence was added to allow for product
      secretion. The construct was introduced into L lactis. Colitis was induced via
      transfer of CD4(+)CD45RB(hi) T cells into Rag(-/-) mice to induce colitis; 7.5
      weeks later, LL-IL-27 was administered to mice via gavage. Intestinal tissues
      were collected and analyzed. RESULTS: LL-IL-27 administration protected mice from
      T-cell transfer-induced enterocolitis and death. LL-IL-27 reduced disease
      activity scores, pathology features of large and small bowel, and levels of
      inflammatory cytokines in colonic tissue. LL-IL-27 also reduced the numbers of
      CD4(+) and IL-17(+) T cells in gut-associated lymphoid tissue. The effects of LL
      IL-27 required production of IL-10 by the transferred T cells. LL-IL-27 was more
      effective than either LL-IL-10 or systemic administration of recombinant IL-27 in
      reducing colitis in mice. LL-IL-27 also reduced colitis in mice after
      administration of dextran sodium sulfate. CONCLUSIONS: LL-IL-27 reduces colitis
      in mice by increasing the production of IL-10. Mucosal delivery of LL-IL-27 could
      be a more effective and safer therapy for inflammatory bowel disease.

PMID- 24120479
TI  - Chemotherapy and resection for colorectal metastases.

PMID- 24120480
TI  - Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for
      resectable liver metastases from colorectal cancer (EORTC 40983): long-term
      results of a randomised, controlled, phase 3 trial.
AB  - BACKGROUND: Previous results of the EORTC intergroup trial 40983 showed that
      perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and
      oxaliplatin) increases progression-free survival (PFS) compared with surgery
      alone for patients with initially resectable liver metastases from colorectal
      cancer. Here we present overall survival data after long-term follow-up. METHODS:
      This randomised, controlled, parallel-group, phase 3 study recruited patients
      from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged
      18-80 years who had histologically proven colorectal cancer and up to four liver
      metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or
      surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of
      oxaliplatin 85mg/m(2), folinic acid 200 mg/m(2) (DL form) or 100 mg/m(2) (L form)
      on days 1-2 plus bolus, and fluorouracil 400 mg/m(2) (bolus) and 600 mg/m(2)
      (continuous 22 h infusion), before and after surgery. Patients were centrally
      randomised by minimisation, adjusting for centre and risk score and previous
      adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was
      open label. Analysis of overall survival was by intention to treat in all
      randomly assigned patients. FINDINGS: Between Oct 10, 2000, and July 5, 2004, 364
      patients were randomly assigned to a treatment group (182 patients in each group,
      of which 171 per group were eligible and 152 per group underwent resection). At a
      median follow-up of 8.5 years (IQR 7.6-9.5), 107 (59%) patients in the
      perioperative chemotherapy group had died versus 114 (63%) in the surgery-only
      group (HR 0.88, 95% CI 0.68-1.14; p=0.34). In all randomly assigned patients,
      median overall survival was 61.3 months (95% CI 51.0-83.4) in the perioperative
      chemotherapy group and 54.3 months (41.9-79.4) in the surgery alone group. 5-year
      overall survival was 51.2% (95% CI 43.6-58.3) in the perioperative chemotherapy
      group versus 47.8% (40.3-55.0) in the surgery-only group. Two patients in the
      perioperative chemotherapy group and three in the surgery-only group died from
      complications of protocol surgery, and one patient in the perioperative
      chemotherapy group died possibly as a result of toxicity of protocol treatment.
      INTERPRETATION: We found no difference in overall survival with the addition of
      perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients
      with resectable liver metastases from colorectal cancer. However, the previously
      observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should
      remain the reference treatment for this population of patients. FUNDING:
      Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale
      Contre Cancer, US National Cancer Institute, Sanofi-Aventis.

PMID- 24120481
TI  - Construction of a plasmid for heterologous protein expression with a constitutive
      promoter in Trichoderma reesei.
AB  - Trichoderma reesei is widely used as a host for homologus and heterologus protein
      expression because of its well-known capability of protein secretion, especially
      cellulases secretion. In this study, a binary vector which could be used for
      protein expression was constructed with a constitutive promoter of rp2 gene. This
      vector contained the expression cassette Prp2-target gene-Trp2 and hygromycin B
      selection marker based on pCAMBIA1300 for T-DNA random insertion. The feasibility
      of the promoter was determined by eGFP (enhanced green fluorescence protein)
      expression in T. reesei. For heterologus protein expression, the expression of
      bgla from Aspergillus niger in the transformant was 3 folds higher than that of
      the wild type strain. The results demonstrate that this constitutive promoter
      could be applied for protein expression and thus this protein express system may
      contribute to the industrial protein production. 

PMID- 24120482
TI  - Current situation of tuberculosis in Japan and requirement for new vaccine.

PMID- 24120483
TI  - Sustained functional serotype-specific antibody after primary and secondary
      vaccinations with a pneumococcal polysaccharide vaccine in elderly patients with
      chronic lung disease.
AB  - An observational study was conducted to determine immunogenicity before and after
      primary and secondary vaccinations with 23-valent pneumococcal polysaccharide
      vaccine in a cohort of 40 elderly patients with chronic lung diseases. Safety of
      this vaccine was also compared between primary and secondary vaccination. We
      analyzed serotype-specific immunoglobulin G (IgG) and the opsonization index (OI)
      for serotypes 6B, 14, 19F, and 23F and compared adverse local and systemic
      reactions. The levels of serotype-specific IgG and the OIs significantly
      increased 1 month after primary and secondary vaccinations. Peak levels of IgG
      after secondary vaccination were 5-20% lower than those after primary
      vaccination, while serotype-specific OIs after secondary vaccination were
      comparable with those after primary vaccination. The levels of serotype-specific
      IgG required for 50% killing significantly decreased 1 month after vaccination.
      These values for serotypes 14, 19F, and 23F were slightly elevated immediately
      before secondary vaccination, but those for serotype 6B did not change. After
      secondary vaccination, these values declined slightly for serotypes 14, 19F, and
      23F and remained low for serotype 6B. Although self-limited local and systemic
      reactions were more frequent after secondary vaccination compared with primary
      vaccination, no serious systemic reaction was found after either vaccination. Our
      data suggest a sustained functional serotype-specific IgG after primary and
      secondary vaccination and confirmed the safety of secondary vaccination among
      elderly individuals with chronic lung disease. 

PMID- 24120485
TI  - Development of pneumococcal polysaccharide conjugate vaccine with long spacer
      arm.
AB  - Streptococcus pneumoniae is a serious Gram-positive pathogen responsible for
      several life-threatening pneumococcal diseases. Pneumococcal capsular
      polysaccharide (CPS) is a key virulence determinant of S. pneumoniae and its
      immunogenicity can be improved by conjugation with a carrier protein. Reductive
      amination, the most widely used approach for pneumococcal CPS conjugate vaccine
      (PCV), suffers from low conjugation efficiency and the problem of steric
      hindrance. Here, copper-catalyzed azide-alkyne cycloaddition was used for
      development of PCV with long spacer arm (L-PCV). Tetanus toxoid (TT) was used as
      the carrier protein. The long spacer arm in L-PCV can minimize the problem of
      steric hindrance between CPS and TT, thereby improving the CPS-specific antibody
      titers in the mice model. L-PCV can also induce high avidity functional antibody
      and elicit immunological memory in response to the native CPS. 

PMID- 24120486
TI  - Salmonid alphavirus replicon is functional in fish, mammalian and insect cells
      and in vivo in shrimps (Litopenaeus vannamei).
AB  - The Salmonid alphavirus (SAV) is the etiological agent of pancreas disease in
      Atlantic salmon (Salmo salar) and Sleeping disease in rainbow trout (Oncorhynchus
      mykiss). SAV differs from alphaviruses infecting terrestrial animals in that it
      infects salmonid fish at low temperatures and does not use an arthropod vector
      for transmission. In this study we have shown that a SAVbased replicon could
      express proteins when driven by the subgenomic promoter in vitro in cells from
      fish, mammals and insects, as well as in vivo in shrimps (Litopanaeus vannamei).
      The SAV-replicon was found to be functional at temperatures ranging from 4 to 37
      degrees C. Protein expression was slow and moderate compared to that reported
      from terrestrial alphavirus replicons or from vectors where protein expression
      was under control of the immediate early CMV-promoter. No cytopathic effect was
      visually observable in cells transfected with SAV-replicon vectors. Double
      stranded RNA was present for several days after transfection of the SAV-replicon
      in fish cell lines and its presence was indicated also in shrimp. The combination
      of prolonged dsRNA production, low toxicity, and wide temperature range for
      expression, may potentially be advantageous for the use of the SAV replicon to
      induce immune responses in aquaculture of fish and shrimp. 

PMID- 24120484
TI  - Protein coated microcrystals formulated with model antigens and modified with
      calcium phosphate exhibit enhanced phagocytosis and immunogenicity.
AB  - Protein-coated microcrystals (PCMCs) were investigated as potential vaccine
      formulations for a range of model antigens. Presentation of antigens as PCMCs
      increased the antigen-specific IgG responses for all antigens tested, compared to
      soluble antigens. When compared to conventional aluminium-adjuvanted
      formulations, PCMCs modified with calcium phosphate (CaP) showed enhanced antigen
      specific IgG responses and a decreased antigen-specific IgG1:IgG2a ratio,
      indicating the induction of a more balanced Th1/Th2 response. The rate of antigen
      release from CaP PCMCs, in vitro, decreased strongly with increasing CaP loading
      but their immunogenicity in vivo was not significantly different, suggesting the
      adjuvanticity was not due to a depot effect. Notably, it was found that CaP
      modification enhanced the phagocytosis of fluorescent antigen-PCMC particles by
      J774.2 murine monocyte/macrophage cells compared to soluble antigen or soluble
      PCMCs. Thus, CaP PCMCs may provide an alternative to conventional aluminium-based
      acellular vaccines to provide a more balanced Th1/Th2 immune response. 

PMID- 24120487
TI  - 160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker
      Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is a severe muscular dystrophy with eye and brain
      malformations. On a molecular level, WWS is a disorder of the O-linked
      glycosylation of alpha-dystroglycan and therefore referred to as one of the
      dystroglycanopathies. The disease family of muscular dystrophy-dystroglycanopathy
      (MDDG) contains a spectrum of severe to mild disorders, designated as MDDG type A
      to C. WWS, as the most severe manifestation, corresponds to MDDG type A. Defects
      in the genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GTDC2, G3GALNT2, GMPPB,
      B3GNT1, TMEM5 and COL4A1 and ISPD have been described as causal for several types
      of MDDG including WWS, but can only be confirmed in about 60-70% of the
      clinically diagnosed individuals. The proteins encoded by these genes are
      involved in the posttranslational modification of alpha-dystroglycan. Mutations
      in POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GMPPB, TMEM5 and COL4A1 and ISPD
      lead to a wide spectrum of phenotypes of congenital muscular dystrophies with or
      without eye and brain abnormalities. Patients with WWS frequently demonstrate a
      complete lack of psychomotor development, severe eye malformations, cobblestone
      lissencephaly and a hypoplastic cerebellum and brainstem, seizures, hydrocephalus
      and poor prognosis. Here, we present a boy with WWS who showed compound
      heterozygous changes in ISPD and discuss the clinical and radiological phenotype
      and the molecular genetic findings, including a novel pathogenic mutation in
      ISPD.

PMID- 24120488
TI  - Cg-SoxE and Cg-beta-catenin, two new potential actors of the sex-determining
      pathway in a hermaphrodite lophotrochozoan, the Pacific oyster Crassostrea gigas.
AB  - Sex determination is poorly known in mollusks, lophotrochozoa and most
      hermaphrodites. In the oyster Crassostrea gigas, an irregular successive
      hermaphrodite, sex determination may occur at the end of a gametogenetic cycle to
      prepare the next cycle. To investigate further into these aspects we have focused
      on orthologs of SoxE and beta-catenin, key players of the male and female gonadic
      differentiation respectively in mammals. Based on phylogenetic analyses, Cg-SoxE,
      the oyster's SoxE ortholog, is closely related to vertebrate SoxE genes while Cg
      beta-catenin, the oyster's beta-catenin ortholog, is classified amongst
      lophotrochozoa. The mRNA expression measured by qPCR in the gonadic area during a
      gametogenetic cycle is maximal for Cg-SoxE when sex is indiscernible and for Cg
      beta-catenin in mature females. Both expressions are localized from early germ
      cells to spermatocytes and pre-vitellogenic oocytes, and potentially in somatic
      cells. Cg-beta-catenin is also expressed in vitellogenic oocytes. These actors
      may be involved in early oyster gonadic differentiation, which includes sex
      determination. Our results enhance the understanding of sex determination in C.
      gigas and in mollusks and they provide additional knowledge in compared genomics
      of reproduction and in molecular phylogeny. 

PMID- 24120489
TI  - Alpha-fetoprotein, a fascinating protein and biomarker in neurology.
AB  - Alpha-fetoprotein (AFP) is present in fetal serum in concentrations up to
      5,000,000 MUg/l. After birth, AFP gene expression is turned down with a
      subsequent fall of the serum concentrations of this albumin-like protein to
      'adult values' of circa 0.5-15 MUg/l from the age of 2 years onwards.
      Irrespective of its assumed important functions, individuals with AFP deficiency
      appear fully healthy. The other way around, the presence of AFP in the
      circulation after the first years of life doesn't seem to harm, since individuals
      with 'hereditary persistence of AFP' are also without clinical abnormalities.
      During pregnancy, AFP (in maternal serum) has long been recognized as a marker
      for congenital anomalies of the fetus. Equally well known is AFP as biomarker for
      hepatocellular carcinoma and some other malignancies. There are at least four
      neurodegenerative disorders, all inherited as autosomal recessive traits and
      characterized by the presence of cerebellar ataxia, abnormal ocular movements,
      and neuropathy, for which an elevated concentration of serum AFP is an important
      diagnostic biomarker. The availability of a reliable biomarker is not only
      important during screening or diagnostic processes, but is also relevant for
      objective follow-up during (future) therapeutic interventions.

PMID- 24120491
TI  - Establishment of a reliable and reproducible murine osteoarthritis model.
AB  - OBJECTIVE: Many osteoarthritis (OA) models have been developed in mice to
      understand OA progression and evaluate new OA therapies. However, the individual
      variation of the joint lesions remains a critical problem in most of the current
      OA models. We established an OA model in C57BL/6 mice that is more reproducible
      and amenable to therapeutic intervention by controlling their movement. DESIGN:
      OA was induced in 9-week-old C57BL/6 mice by destabilizing the medial meniscus.
      The mice were then raised in the standard cage for free movement or in a confined
      cage customized to restrict movement. Mice in the confined cage were subjected to
      no exercise or exercise of 400, 800, and 1200 m/day. RESULTS: OA lesions of mice
      in the confined cage were more severe in the exercise group and showed much less
      variation. However, the patterns of OA lesions over time were quite different
      depending on the amount of daily exercise; the patterns increased linearly until
      8 weeks in 400 m/day exercise group, but showed plateauing after 4 weeks in 800
      m/day and 1200 m/day groups. The validity of our novel OA model with movement
      control was proven by successfully discriminating the therapeutic effect of
      hyaluronic acid (HA) in histological scores, while the OA model using standard
      caging showed a statistically insignificant difference. CONCLUSION: The mouse OA
      model using the confine cage and enforced periodic exercise of mice is more
      reproducible and reliable than standard caging methods.

PMID- 24120490
TI  - Autophagy is activated in compression-induced cell degeneration and is mediated
      by reactive oxygen species in nucleus pulposus cells exposed to compression.
AB  - OBJECTIVE: To determine whether autophagy contributes to the pathogenesis of
      degenerative disc disease (DDD) or retards the intervertebral disc (IVD)
      degeneration, and investigate the possible relationship between compression
      induced autophagy and intracellular reactive oxygen species (ROS) in nucleus
      pulposus (NP) cells in vitro. METHODS: The autophagosome and autophagy-related
      markers were used to explore the role of autophagy in rat NP cells under
      compressive stress, which were measured directly by electronic microscopy,
      monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and
      indirectly by analyzing the impact of pharmacological inhibitors of autophagy
      such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between
      autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)
      fluorescein staining. In addition, ROS were measured to determine whether these
      factors are responsible for the development of compression-induced autophagy.
      RESULTS: Our results indicated that rat NP cells activated autophagy in response
      to the same strong apoptotic stimuli that triggered apoptosis by compression.
      Autophagy and apoptosis were interconnected and coordinated in rat NP cells
      exposed to compression stimuli. Compression-induced autophagy was closely related
      to intracellular ROS production. CONCLUSIONS: Enhanced degradation of damaged
      components of NP cells by autophagy may be a crucial survival response against
      mechanical overload, and extensive autophagy may trigger autophagic cell death.
      Regulating autophagy and reducing the generation of intracellular ROS may retard
      IVD degeneration.

PMID- 24120492
TI  - Cationic lipid nanosystems as carriers for nucleic acids.
AB  - Solid lipid nanoparticles (SLNs) consisting of tristearin or tribehenin, and
      monoolein aqueous dispersions (MADs) consisting of glyceryl-monoolein have been
      studied as potential nanocarriers for nucleic acids. The cationic character of
      nanocarriers was obtained by adding cationic surfactants, such as
      diisobutylphenoxyethyl-dimethylbenzyl ammonium chloride (DEBDA) or PEG-15
      Cocopolyamine (PCPA), to the lipid composition. The products were characterised
      in terms of size and morphology by Cryo-TEM and PCS. The charge properties were
      determined by measuring the zeta potential. Our experimental protocol enabled us
      to obtain homogeneous and stable cationic nanosystems within 3-6 months of
      production. Assessment of cytotoxicity on HepG2 cells by MTT assays indicated
      that MAD preparations were less toxic than SLN, and in general PCPA-containing
      formulations are less cytotoxic than DEBDA-containing ones. The formation of
      electrostatic complexes with salmon sperm or plasmid DNA, used as model nucleic
      acids, was evaluated by electrophoresis on agarose gel. The results confirmed
      that all the formulations studied are able to form the complex. Finally, we
      investigated the ability of SLN and MAD to deliver DNA into HepG2 cells, and to
      this purpose we exploited expression plasmids for green fluorescent protein or
      firefly luciferase. Although with reduced efficiency, the results showed that the
      produced nanocarriers are able to convey plasmids into cells. The data obtained
      encourage further study aimed at improving these new formulations and proposing
      them as novel in vitro transfection reagents with potential application to in
      vivo delivery of nucleic acids.

PMID- 24120493
TI  - Generation of HER2 monoclonal antibodies using epitopes of a rabbit polyclonal
      antibody.
AB  - One of the issues in using polyclonal antibodies is the limited amount of reagent
      available from an immunisation, leading to batch-to-batch variation and
      difficulties in obtaining the same antibody performance when the same antigen is
      re-immunised into several separate animals. This led to the development of
      hybridoma technology allowing, at least theoretically, for an unlimited
      production of a specific binder. Nevertheless, polyclonal antibodies are widely
      used in research and diagnostics and there exists a need for robust methods to
      convert a polyclonal antibody with good binding performance into a renewable
      monoclonal with identical or similar binding specificity. Here we have used
      precise information regarding the functional recognition sequence (epitope) of a
      rabbit polyclonal antibody with attractive binding characteristics as the basis
      for generation of a renewable mouse monoclonal antibody. First, the original
      protein fragment antigen was used for immunisation and generation of mouse
      hybridoma, without obtaining binders to the same epitope region. Instead a
      peptide designed using the functional epitope and structural information was
      synthesised and used for hybridoma production. Several of the monoclonal
      antibodies generated were found to have similar binding characteristics to those
      of the original polyclonal antibody. These monoclonal antibodies detected native
      HER2 on cell lines and were also able to stain HER2 in immunohistochemistry using
      xenografted mice, as well as human normal and cancer tissues.

PMID- 24120494
TI  - Transfusion support of autoimmune hemolytic anemia: how could the blood group
      genotyping help?
AB  - Conventional pretransfusion testing based on hemagglutination assays can be
      challenging for patients with autoimmune hemolytic anemia (AIHA) because of the
      presence of auto-antibodies. It has been suggested that deoxyribonucleic acid
      based methods could be more efficient in the selection of antigen-matched red
      blood cell units in those settings. Because of the high risk of alloimmunization
      of these patients and the labor-intensive nature of adsorption techniques, we
      decided to evaluate the feasibility of selecting antigen-matched units on the
      basis of RBC genotyping. We included in our routine RBC genotyping program
      samples from 7 patients with AIHA presenting a strongly positive direct
      antiglobulin test. This made the routine compatibility tests difficult. Most
      patients had previously received transfusions because of warm AIHA. Matched donor
      units were selected according to the genotype. For all but 1 patient, blood group
      genotyping could be done on time to allow antigen-matched transfusion. Four
      patients received antigen-matched red blood cell units based on RBC genotyping
      and for 1 patient the fact that no matched units were available led us to
      postpone the transfusion. After each transfusion, the recovery was recorded and
      considered satisfactory for all transfused patients. 

PMID- 24120495
TI  - Exercise training attenuates adipose tissue fibrosis in diet-induced obese mice.
AB  - Tissue fibrosis, such as that which occurs in obesity, is associated with chronic
      inflammatory diseases. Although regular exercise reduces adipose tissue
      inflammation, the mechanisms regulating the effects of exercise on adipose tissue
      fibrosis are unclear. This study aimed to clarify whether exercise training
      attenuates adipose tissue fibrosis with consequent reduction of extracellular
      matrix including collagens. Male C57BL/6J (4-week old) mice were randomly
      assigned to four groups that received a normal diet (ND) plus sedentary (n=8), an
      ND plus exercise training (n=8), a high-fat diet (HFD) plus sedentary (n=12), and
      an HFD plus exercise training (n=12). Mice were fed the ND or HFD from 4 to 20
      weeks of age. The exercise groups were trained on a motorized treadmill for 60
      min/day, 5 times/week over the same period. Histological hepatic fibrosis
      detected by Sirius red and alpha-smooth muscle actin staining were attenuated in
      HFD exercise mice compared with HFD sedentary mice. mRNA levels of transforming
      growth factor-beta and tissue inhibitors of metalloproteinase-1, major regulators
      of tissue fibrosis, were increased in HFD sedentary mice but were attenuated in
      HFD exercise mice. Similarly, adipose tissue from the HFD sedentary mice
      contained higher macrophages than adipose tissue from the ND mice, and this was
      also lowered by exercise training. These findings suggest that exercise training
      may be effective for attenuating adipose tissue inflammation in obesity.

PMID- 24120496
TI  - Exercise-induced enhancement of insulin sensitivity is associated with
      accumulation of M2-polarized macrophages in mouse skeletal muscle.
AB  - Exercise enhances insulin sensitivity in skeletal muscle, but the underlying
      mechanism remains obscure. Recent data suggest that alternatively activated M2
      macrophages enhance insulin sensitivity in insulin target organs such as adipose
      tissue and liver. Therefore, the aim of this study was to determine the role of
      anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin
      sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill
      running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2
      deoxy glucose uptake was found to be increased in plantaris muscle. This change
      was associated with increased number of CD163-expressing macrophages (i.e. M2
      polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by
      pretreatment of mice with clodronate-containing liposome abrogated both CD163
      positive macrophage accumulation in skeletal muscle as well as the enhancement of
      insulin sensitivity after exercise, without affecting insulin-induced
      phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These
      results suggest that accumulation of M2-polarized macrophages is involved in
      exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle,
      independently of the phosphorylation of Akt and AS160 and expression of GLUT4.

PMID- 24120497
TI  - Cysteine 295 indirectly affects Ni coordination of carbon monoxide dehydrogenase
      II C-cluster.
AB  - A unique [Ni-Fe-S] cluster (C-cluster) constitutes the active center of Ni
      containing carbon monoxide dehydrogenases (CODHs). His(261), which coordinates
      one of the Fe atoms with Cys(295), is suggested to be the only residue required
      for Ni coordination in the C-cluster. To evaluate the role of Cys(295), we
      constructed CODH-II variants. Ala substitution for the Cys(295) substitution
      resulted in the decrease of Ni content and didn't result in major change of Fe
      content. In addition, the substitution had no effect on the ability to assemble a
      full complement of [Fe-S] clusters. This strongly suggests Cys(295) indirectly
      and His(261) together affect Ni-coordination in the C-cluster. 

PMID- 24120498
TI  - CD34-negative mesenchymal stem-like cells may act as the cellular origin of human
      aortic valve calcification.
AB  - Although various osteogenic inducers contribute to the calcification of human
      aortic valve interstitial cells, the cellular origin of calcification remains
      unclear. We immunohistochemically investigated the cellular origin of valve
      calcification using enzymatically isolated cells from both calcified and non
      calcified human aortic valve specimens. CD73-, 90-, and 105-positive and CD45
      negative mesenchymal stem-like cells (MSLCs) were isolated from both types of
      valve specimens using fluorescence-activated cell sorting. MSLCs were further
      sorted into CD34-negative and -positive cells. Compared with CD34-positive cells,
      CD34-negative MSLCs were significantly more sensitive to high inorganic phosphate
      (3.2 mM), calcifying easily in response. Furthermore, immunohistochemical
      staining showed that significantly higher numbers (~7-9-fold) of CD34-negative
      compared with CD34-positive MSLCs were localized in calcified aortic valve
      specimens obtained from calcified aortic stenosis patients. These results suggest
      that CD34-negative MSLCs are responsible for calcification of the aortic valve.

PMID- 24120499
TI  - Extra-structural elements in the RNA recognition motif in archaeal Pop5 play a
      crucial role in the activation of RNase P RNA from Pyrococcus horikoshii OT3.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein complex essential for the
      processing of 5' leader sequences of precursor tRNAs (pre-tRNA). PhoPop5 is an
      archaeal homolog of human RNase P protein hPop5 involved in the activation of
      RNase P RNA (PhopRNA) in the hyperthermophilic archaeon Pyrococcus horikoshii,
      probably by promoting RNA annealing (AN) and RNA strand displacement (SD).
      Although PhoPop5 folds into the RNA recognition motif (RRM), it is distinct from
      the typical RRM in that it has an insertion of alpha-helix (alpha2) between
      alpha1 and beta2. Biochemical and structural data have shown that the
      dimerization of PhoPop5 through the loop between alpha1 and alpha2 is required
      for the activation of PhopRNA. In addition, PhoPop5 has additional helices
      (alpha4 and alpha5) at the C-terminus, which pack against one face of the beta
      sheet. In this study, we examined the contribution of the C-terminal helices to
      the activation of PhopRNA using mutation analyses. Reconstitution experiments and
      fluorescence resonance energy transfer (FRET)-based assays indicated that
      deletion of the C-terminal helices alpha4 and alpha5 significantly influenced on
      the pre-tRNA cleavage activity and abolished AN and SD activities, while that of
      alpha5 had little effect on these activities. Moreover, the FRET assay showed
      that deletion of the loop between alpha1 and alpha2 had no influence on the AN
      and SD activity. Further mutational analyses suggested that basic residues at
      alpha4 are involved in interaction with PhopRNA, while hydrophobic residues at
      alpha4 participate in interaction with hydrophobic residues at the beta-sheet,
      thereby stabilizing an appropriate orientation of the helix alpha4. Together,
      these results indicate that extra-structural elements in the RRM in PhoPop5 play
      a crucial role in the activation of PhopRNA.

PMID- 24120500
TI  - M-CSF receptor mutations in hereditary diffuse leukoencephalopathy with spheroids
      impair not only kinase activity but also surface expression.
AB  - The tyrosine kinase Fms, the cell surface receptor for M-CSF and IL-34, is
      critical for microglial proliferation and differentiation in the brain. Recently,
      a number of mutations have been identified in Fms as a putative genetic cause of
      hereditary diffuse leukoencephalopathy with spheroids (HDLS), implying an
      important role of microglial dysfunction in HDLS pathogenesis. In this study, we
      initially confirmed that 11 mutations, which reside within the ATP-binding or
      major tyrosine kinase domain, caused a severe impairment of ligand-induced Fms
      auto-phosphorylation. Intriguingly, we found that 10 of the 11 mutants also
      showed a weak cell surface expression, which was associated with a concomitant
      increase in the low molecular weight hypo-N-glycosylated immature gp130Fms-like
      species. Indeed, the mutant proteins heavily accumulated to the Golgi-like
      perinuclear regions. These results indicate that all of the Fms mutations tested
      severely impair the kinase activity and most of the mutations also impair the
      trafficking to the cell surface, further suggesting that HDLS is caused by the
      loss of Fms function. 

PMID- 24120501
TI  - miR-196a targets netrin 4 and regulates cell proliferation and migration of
      cervical cancer cells.
AB  - Recent research has uncovered tumor-suppressive and oncogenic potential of miR
      196a in various tumors. However, the expression and mechanism of its function in
      cervical cancer remains unclear. In this study, we assess relative expression of
      miR-196a in cervical premalignant lesions, cervical cancer tissues, and four
      cancer cell lines using quantitative real-time PCR. CaSki and HeLa cells were
      treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the
      role of miR-196a in cancer cell proliferation and migration. We demonstrated that
      miR-196a was overexpressed in cervical intraepithelial neoplasia 2-3 and cervical
      cancer tissue. Moreover, its expression contributes to the proliferation and
      migration of cervical cancer cells, whereas inhibiting its expression led to a
      reduction in proliferation and migration. Five candidate targets of miR-196a
      chosen by computational prediction and Cervical Cancer Gene Database search were
      measured for their mRNA in both miR-196a-overexpressing and -depleted cancer
      cells. Only netrin 4 (NTN4) expression displayed an inverse association with miR
      196a. Fluorescent reporter assays revealed that miR-196a inhibited NTN4
      expression by targeting one binding site in the 3'-untranslated region (3'-UTR)
      of NTN4 mRNA. Furthermore, qPCR and Western blot assays verified NTN4 expression
      was downregulated in cervical cancer tissues compared to normal controls, and in
      vivo mRNA level of NTN4 inversely correlated with miR-196a expression. In
      summary, our findings provide new insights about the functional role of miR-196a
      in cervical carcinogenesis and suggested a potential use of miR-196a for clinical
      diagnosis and as a therapeutic target. 

PMID- 24120502
TI  - Cancer registration, public health and the reform of the European data protection
      framework: Abandoning or improving European public health research?
AB  - The importance of cancer- and other disease registries for planning, management
      and evaluation of healthcare systems has been shown repeatedly during the last 50
      years. Complete and unbiased population-level analyses on routinely collected,
      individual data concerning health and personal characteristics can address
      significant concerns about risk factors for cancer and provide sound evidence
      about public health and the effectiveness of healthcare systems. The existence of
      quality controlled and comprehensive data in registries, allowed to be used for
      quality control, research and public health purposes are taken as granted by most
      health professionals and researchers. However, the current revision of the
      European Union (EU) data protection framework suggests a harmonisation of
      requirements for confidentiality and individual consent to data processing,
      likely at the expense of proper use of registry data in the health sector.
      Consequences of excessive confidentiality rules that may lead to missed data
      linkages have been simulated. The simulations provide one possible explanation
      for observed heterogeneity among some cancer incidence data. Further, public
      health, quality control and epidemiological research on large populations can no
      longer provide evidence for health interventions, if requirements for consent
      renders research impossible or where attempts to obtain consent from each data
      subject generates biased results. Health professionals should engage in the on
      going debate on the Commission's proposal for a General Data Protection
      Regulation. The nature and use of registry data in public health research must be
      explained and known to policy-makers and the public. Use of cancer registry data
      and other epidemiological activity will terminate abruptly if an unnecessarily
      strict EU data protection regulation is adopted. Research based interventions, as
      well as the international recognised standing of cancer registries and register
      based research institutions in Europe are at stake.

PMID- 24120503
TI  - Immunostimulatory effect of artificial feed supplemented with indigenous plants
      on Clarias gariepinus against Aeromonas hydrophila.
AB  - The antibacterial activity of methanol extracts of Ficus benghalensis (prop-root)
      and Leucaena leucocephala (pod seed) was evaluated by measurement of zone of
      inhibition against pathogenic bacteria, Escherichia coli and Aeromonas
      hydrophila. Control artificial feed and artificial feed supplemented with 5%
      powder of F. benghalensis and L. leucocephala were prepared. Juvenile Clarias
      gariepinus were divided into four groups, acclimatized to laboratory conditions
      and fed with respective feeds for 20 days prior to the experiment.
      Immunomodulatory response of supplementary feed was studied by challenging the
      fish intraperitoneally at weekly intervals, with A. hydrophila. One set of fish,
      not challenged with A. hydrophila was used as a negative control, to analyze any
      detrimental effect of supplementary feed, while positive control, comprised of
      challenged fish fed with non-supplemented feed. Other two groups of fish were
      challenged with A. hydrophila and fed with respective supplementary feeds. Blood
      was collected on weekly intervals for four weeks and serum samples were analyzed
      to evaluate the damage of fish by A. hydrophila through liver function tests. The
      increase in the levels of Serum glutamic oxaloacetic transaminase (SGOT) and
      Serum Glutamic pyruvate transaminase (SGPT) in positive control group indicated
      the damage of liver & kidney. However the levels did not change significantly in
      fish fed with supplementary feeds when compared to negative control group. Nitric
      oxide, SOD, ALP and lipid peroxidase indicated lower stress levels in these fish
      compared to positive control. Fish fed with supplementary feed showed increased
      lysozyme activity and phagocytic index indicating an increase in non-specific
      immune response. The immunoglobulin levels of in serum were analyzed by
      homologous sandwich ELISA, which showed higher antibody production in fish fed
      with supplementary feed. The current study suggests conclusively,
      immunostimulatory role of F. benghalensis (prop-roots) and L. leucocephala (pod
      seed) in C. gariepinus when supplemented in artificial feed.

PMID- 24120504
TI  - The biofunction of orange-spotted grouper (Epinephelus coioides) CC chemokine
      ligand 4 (CCL4) in innate and adaptive immunity.
AB  - CC chemokine (motif) ligand 4 (CCL4) is indispensable to the chemoattraction of
      macrophages, natural killer cells, and lymphocytes in mammals; however, it has
      only been cloned in a limited number of fish species and information related to
      its biofunction remains ambiguous with regard to teleosts. To explore the role of
      teleost CCL4, we first evaluated the mRNA expression of the Epinephelus coioides
      CCL4 (gCCL4) gene in various organs under LPS and poly (I:C) stimulated;
      secondary, we evaluated the immune-related genes expression of fish under the
      recombinant gCCL4 protein stimulated. Our results revealed an increase in the
      mRNA of gCCL4 in immune organs immediately following stimulation by poly (I:C);
      however, in LPS stimulated fish, the expression did not increase until nearly 24
      h after induction. In biofunction assays, recombinant gCCL4 was found to induce
      chemotactic activity in the peripheral blood leukocytes of groupers and up
      regulate the gene expressions of grouper TNFA1 (TNF-alpha1), TNFA2 (TNF-alpha2),
      IFNG (IFN-gamma), MX, TBX21 (T-bet), CD8 (alpha and beta chain). These findings
      indicate that grouper CCL4 attracts leukocytes, induces an inflammatory response,
      and drives lymphocyte differentiation into the Th1 pathway.

PMID- 24120505
TI  - Sesquiterpene action, and morphogenetic signaling through the ortholog of
      retinoid X receptor, in higher Diptera.
AB  - Morphogenetic signaling by small terpenoid hormones is a common feature of both
      vertebrate and invertebrate development. Most attention on insect developmental
      signaling by small terpenoids has focused on signaling by juvenile hormone
      through bHLH-PAS proteins (e.g., the MET protein), especially as that signaling
      axis intersects with ecdysteroid action through the receptor EcR. However, a
      series of endocrine and pharmacological studies on pupariation in cyclorrhaphous
      Diptera have remained persistently refractory to explanation with the above two
      axis model. Recently, the terpenoid compound methyl farnesoate has been
      physicochemically demonstrated to exist in circulation at physiological
      concentrations, in several mecopterid orders, including Diptera. In addition, it
      has also been recently demonstrated that the receptor to which methyl farnesoate
      binds with nanomolar affinity (ultraspiracle, an ortholog of retinoid X receptor)
      requires a functioning ligand binding pocket to sustain the morphogenetic
      transition to puparium formation. This review evaluates endocrine and
      pharmacological evidence for developmental pathways reached by methyl farnesoate
      action, and assesses the participation of the retinoid X receptor ligand pocket
      in signal transduction to those developmental endpoints.

PMID- 24120506
TI  - Neurosurgical work during the Napoleonic wars: Baron Larrey's experience.
AB  - OBJECTIVES: Considered as the most famous French military surgeon, Dominique-Jean
      Larrey (1766-1842), who joined all the campaigns of Napoleon, wrote his memoirs
      and several medical articles. This paper discusses how in the Napoleonic times,
      Larrey dealt with neurosurgical diseases or injuries. PATIENTS AND METHODS: We
      reviewed four main publications of Larrey published between 1812 and 1838 and
      analyzed the type of neurosurgical cases presented and their treatment. RESULTS:
      These works include his practice of what we call now "neurosurgery" since most
      injuries described concern the skull or spine. He seemed to treat patients with
      humanity, integrity and perseverance. Larrey dealt with many aspects of
      neurosurgery, such as cranial or spinal trauma surgery, and also infectious
      diseases. He saw many head injuries inflicted not only by muskets or artillery,
      but also with spears and sabers. Unlike some others, Larrey advocated the use of
      trepanation in many situations as practiced, for instance, in the treatment of
      depressed fractures or in presence of subdural collections. On the other hand,
      this surgeon who saw thousands of amputees during his career did not mention the
      phantom limb phenomenon in his memoirs. Similarly, the issue of cerebral
      localizations is only mentioned in his last work, published in 1838. CONCLUSIONS:
      In his work, Larrey (and all his contemporaries) dealt essentially with "cranial"
      surgery, as in skull fractures where the brain could potentially have been
      injured by bone fragments. The time for brain surgery had not come yet.

PMID- 24120507
TI  - Fatigue fracture in dual modular revision total hip arthroplasty stems: failure
      analysis and computed tomography diagnostics in two cases.
AB  - We report on two patients with fracture of a modular, tapered and distally fixed,
      uncemented titanium revision hip stem, not previously described. A failure
      analysis revealed that the cause of the fractures was the development of fatigue
      cracks in the mid-stem cobalt-chromium modular junction ending in corrosion
      fatigue failure. No material defects or stress risers were found in any of the
      implants. The diameter of the mid-stem modular junction might be undersized for
      use in heavy and active patients. We also report a new way of detecting an
      undisplaced fracture at the modular junction, using the scout image from a
      computed tomography (CT) scan; a technique that can be used when plain
      radiographs are inconclusive. 

PMID- 24120508
TI  - P-glycoprotein expression and pharmacological modulation in larval stages of
      Echinococcus granulosus.
AB  - P-glycoprotein (Pgp) is an ATP-dependent transporter involved in the efflux of a
      wide variety of lipophilic substrates, such as toxins and xenobiotics, out of
      cells. Pgp expression level is associated with the ineffective therapeutic
      treatment of cancer cells and microbial pathogens which gives it high clinical
      importance. Research on these transporters in helminths is limited. This work
      describes for the first time the Echinococcus granulosus Pgp (Eg-Pgp) expression,
      in a model cestode parasite and an important human pathogen. Based on calcein
      efflux assays in the presence of common Pgp modulators, we demonstrated the
      occurrence of active Eg-Pgp in protoscoleces and metacestodes. Eg-Pgp, which
      showed a molecular mass of ~130 kDa in western blots, is localized in the suckers
      and the tegument of control protoscoleces as well as in the subtegument or all
      parenchymatous cells of protoscoleces treated with Pgp-interfering agents. We
      also identified five genes encoding Pgp which are constitutively expressed in
      protoscoleces and metacestodes. We showed that the Eg-pgp1 and Eg-pgp2
      transcripts were up-regulated in response to in vitro drug treatment with
      amiodarone and loperamide, in agreement with the increased polypeptide levels.
      Finally, in vitro treatment of protoscoleces and metacestodes with
      trifluoperazine and loperamide was lethal to the parasites. This indicates that
      both drugs as well as cyclosporine A negatively modulate the E. granulosus Pgp
      efflux activity, favoring the retention of these drugs in the larval tissue.
      These events could be associated with the reduction in protoscolex and
      metacestode viability.

PMID- 24120509
TI  - CD8+ lymphocytes and apoptosis in typical and atypical medullary carcinomas of
      the breast.
AB  - Medullary breast carcinoma (MBC) is a form of ductal invasive carcinoma (DIC)
      characterized by an abundant infiltration of the tumour by lymphocytes. MBC has
      been classified histologically into typical medullary carcinoma (TMC) and
      atypical medullary carcinoma (AMC), with TMC having a better prognosis than AMC
      and other DIC. The distribution of CD8+ lymphocytes within tumour nests and
      lymphocyte tracts, and apoptosis in lymphocytes and tumour cells within tumour
      nests, were studied in archived formalin fixed and paraffin embedded tissues of
      TMC and AMC. CD8+ lymphocytes tend to accumulate along the margins of lymphocyte
      tracts that adjoin tumour nests. There were significantly more CD8+ lymphocytes
      within tumour nests of TMC than AMC. TMC also tended to have more CD8+
      lymphocytes within lymphocyte tracts than AMC. Apoptosis of lymphocytes in
      contact with tumour cells and of tumour cells in contact with lymphocytes was
      observed in both AMC and TMC within tumour nests but differences in the
      proportions of apoptotic tumour cells and lymphocytes between the two tumour
      types could not be established. The findings are consistent with CD8+ cytotoxic
      lymphocyte-mediated immunity contributing to the more favourable prognosis for
      TMC compared to AMC. 

PMID- 24120510
TI  - Identification of the polymorphisms in IFITM1 gene and their association in a
      Korean population with ulcerative colitis.
AB  - Interferon inducible transmembrane protein (IFITM) family genes have been
      implicated in several cellular processes such as the homotypic cell adhesion
      functions of IFNs and cellular anti-proliferative activities. We previously
      showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with
      susceptibility to ulcerative colitis (UC). The present study aimed to investigate
      whether the polymorphisms in the IFITM1 gene are associated with susceptibility
      to UC. We also evaluated the expression levels in the putative functional
      promoter polymorphisms to determine the change of their activity. Gene expression
      profiles in the tissues obtained from human digestive tracts by RT-PCR, and the
      possible variation sites and SNPs of IFITM1 were identified by direct sequencing
      method. Genotype analysis in the IFITM1 SNPs was performed by high resolution
      melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs
      for multiple loci were estimated using the expectation maximization (EM)
      algorithm. The expression levels in the putative functional promoter
      polymorphisms were evaluated by performing a luciferase reporter assay. We
      identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA
      (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA
      (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A
      polymorphism of IFITM1 gene in the UC patients were significantly different from
      those of the healthy controls (P=0.002 and 0.042, respectively). These results
      suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with
      susceptibility to UC. 

PMID- 24120511
TI  - Lactobacillus crispatus modulates epithelial cell defense against Candida
      albicans through Toll-like receptors 2 and 4, interleukin 8 and human beta
      defensins 2 and 3.
AB  - Lactobacilli are members of the normal mucosal microflora of most animals.
      Probiotic bacteria, such as Lactobacilli, play a major role in the maintenance of
      a healthy urogenital tract by preventing the colonization of pathogenic bacteria.
      The potentially probiotic strain Lactobacillus crispatus (ATCC 33820) was
      investigated for its capacity to influence the innate immune response of HeLa
      epithelial cells to Candida albicans. In addition, its capacity to modulate the
      toll-like receptor (TLR) expression of HeLa cells was investigated by Western
      blot. When HeLa cells were pre-treated with the L. crispatus and infected with C.
      albicans, the interleukin-8 levels were significantly lower than without pre
      treatment. Also, the effect of L. crispatus on innate immunity was enhanced by
      its capacity to increase the effect of human beta-defensin 3 against C. albicans
      growth. Pre-treating HeLa cells with L. crispatus attenuated the yeast's
      virulence, as demonstrated by its reduced adhesion and growth on human epithelial
      cells. Our findings indicated, also, that after contact with C. albicans,
      epithelial cells expressed more TLR2/4 than non-infected cells, whereas pre
      treatment with L. crispatus downregulated the TLR2/4 expression by epithelial
      cells stimulated with C. albicans. In conclusion, our results show that L.
      crispatus promotes epithelial cell defense against C. albicans infection through
      the involvement of TLR2/4, IL-8 and human beta-defensin 2 and 3, thus suggesting
      a probiotic potential of this Lactobacillus as an anti-infective agent against C.
      albicans. 

PMID- 24120512
TI  - Editorial comment.

PMID- 24120514
TI  - Editorial comment.

PMID- 24120515
TI  - Editorial comment.

PMID- 24120516
TI  - A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with
      potent antimalarial activity against a multidrug resistant Plasmodium falciparum
      strain.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aerial components of Meconopsis simplicifolia
      (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating
      malaria, coughs and colds, and the infections of the liver, lung and blood. This
      study is to validate the ethnopharmacological uses of this plant and also
      identify potent antimalarial drug leads through bioassays of its crude extracts
      and phytochemical constituents. MATERIALS AND METHODS: Meconopsis simplicifolia
      (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was
      subjected to acid-base fractionation. Through repeated extractions, separations
      and spectroscopic analysis, the alkaloids obtained were identified and tested for
      their antimalarial and cytotoxicity activities. RESULTS: Phytochemical studies
      resulted in the isolation of one new protoberberine type alkaloid which we named
      as simplicifolianine and five known alkaloids: protopine, norsanguinarine,
      dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the
      five of the alkaloids tested, simplicifolianine showed the most potent
      antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2
      (chloroquine-antifolate sensitive strain) and K1CB1 (multidrug resistant strain)
      with IC50 values of 0.78 MUg/mL and 1.29 MUg/mL, respectively. The compounds
      tested did not show any significant cytotoxicity activities against human oral
      carcinoma KB cells and normal Vero cells of African kidney epithelial cells.
      CONCLUSIONS: This study validated the traditional uses of the plant for the
      treatment of malaria and identified a new alkaloid, simplicifolianine as a
      potential antimalarial drug lead.

PMID- 24120517
TI  - Evaluation of symptom, clinical chemistry and metabolomics profiles during
      Rehmannia six formula (R6) treatment: an integrated and personalized data
      analysis approach.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannia Six Formula (R6, Chinese name is Liu
      Wei Di Huang Wan) is one of the most important classic Chinese medicine formula
      used to treat metabolic disorders related to aging. It was first reported in the
      Chinese medicine book titled 'Xiao Er Yao Zheng Zhi Jue by Qian Yi' (Chinese Song
      dynasty: 1035-1117). In modern times it is therefore often used to treat
      diabetes, pre-diabetes, fatigue and people with metabolic syndrome. The aim of
      this study is to measure changes in symptoms, clinical parameters and serum
      metabolite profiles during R6 treatment of human subjects with features of
      metabolic syndrome. MATERIALS AND METHODS: Symptoms, clinical parameters and
      serum metabolites were measured before and after 4 and 8 weeks of R6 treatment.
      Nonlinear Principal Component Analysis was applied for the first time to conduct
      an integrated analysis of the three data sets. Correlation structures were
      compared before treatment and after 4 and 8 weeks of treatment. Additionally, a
      State Space Grid approach was used to study personalized changes in symptom
      profiles. RESULTS: The symptoms 'hectic fever' and 'spontaneous sweating' were
      found to be most relieved during R6 treatment. Most of the symptoms were less
      correlated with other variables after 8 weeks of R6 treatment. LDL-C, total
      cholesterol, systolic blood pressure and waist size were found to decrease during
      R6 treatment. Additionally, 10 of the 15 measured phosphatidylcholines were found
      to decrease. Personalized symptom profiles as described by Chinese medical terms
      show that most Yin deficiencies are addressed first by R6 treatment. However, in
      subjects with reduced or less Yin deficiency but which do have a substantial Qi
      deficiency a reduction of Qi deficiency is subsequently observed. CONCLUSIONS: R6
      treatment was shown to improve the lipid profile indicating a reduction of
      cardiovascular risk. Additionally, the changes observed in correlation structure
      indicate a different angle of looking at treatment effects. Less strong
      correlations between symptoms and metabolites suggest a healthier situation after
      R6 treatment. A State Space Grid analysis showed that the effect of R6 was
      different for the Yin deficiency subjects and the Qi deficiency subjects. The
      observed decrease of Yin deficiency related symptoms is in agreement with the use
      of R6 in Chinese medicine to nourish Yin. Observing individual differences in
      treatment effects is therefore an essential step in the development of
      personalized medicine.

PMID- 24120518
TI  - Decoctions from Citrus reticulata Blanco seeds protect the uroepithelium against
      Escherichia coli invasion.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional usage suggests Citrus reticulata
      Blanco seeds have beneficial effects against infection. The purpose of this study
      was to investigate the effect of Citrus reticulata on the uroepithelium and to
      determine the mechanisms responsible for protection against urinary tract
      infection (UTI). MATERIALS AND METHODS: Human bladder cell lines T24 and 5637
      were employed in a cell culture infection model to determine the effects of
      Citrus reticulata treatment on Escherichia coli adherence and invasion of the
      uroepithelium. beta1 integrin and caveolin-1 mRNA expression was assessed using
      RT real-time PCR. beta1 integrin protein expression was confirmed by Western
      Blot. The effect of Citrus reticulata on bacteria was investigated using
      antibacterial sensitivity, yeast agglutination and biofilm assays. RESULTS:
      Citrus reticulata treatment decreased beta1 integrin expression and reduced
      bacterial invasion while adhesion of uroepithelial cells was not affected.
      Caveolin-1 expression was not influenced either and Citrus reticulata did neither
      exhibit any direct antimicrobial effect nor interfered with type 1 fimbriae
      binding. CONCLUSIONS: Our results show that Citrus reticulata has a protective
      effect on the uroepithelium as seen by reduced bacterial invasion of
      uroepithelial cells. These properties suggest that seeds from Citrus reticulata
      may have therapeutic potential in preventing UTI.

PMID- 24120519
TI  - Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L.
      (Caricaceae) pulp extract in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya has been used in the Ethiopian
      traditional medicine to relieve stress and other disease conditions. AIM OF THE
      STUDY: The present study was undertaken to evaluate the anxiolytic and sedative
      effects of 80% ethanolic Carica papaya (Caricaceae) pulp extract in mice.
      MATERIALS AND METHODS: Carica papaya pulp extract was screened for anxiolytic
      effect by using elevated plus maze, staircase and open field tests, and ketamine
      induced sleeping time test for sedation at doses of 50, 100, 200, 400 mg/kg.
      Distilled water and Diazepam were employed as negative and positive control
      groups, respectively. RESULTS: Carica papaya pulp extract 100 mg/kg significantly
      increased the percentage of open arm time and entry, and reduced the percentage
      of entry and time spent in closed arm in elevated plus maze test; reduced the
      number of rearing in the staircase test; and increased the time spent and entries
      in the central squares while the total number of entries into the open field were
      not significantly affected, suggesting anxiolytic activity without altering
      locomotor and sedative effects. A synergistic reduction in the number of rearing
      and an inverted U-shaped dose response curves were obtained with important
      parameters of anxiety CONCLUSIONS: The results of this study established a
      support for the traditional usage of Carica papaya as anxiolytic medicinal plant.

PMID- 24120520
TI  - Herp depletion protects from protein aggregation by up-regulating autophagy.
AB  - Herp is an endoplasmic reticulum (ER) stress inducible protein that participates
      in the ER-associated protein degradation (ERAD) pathway. However, the
      contribution of Herp to other protein degradation pathways like autophagy and its
      connection to other types of stress responses remain unknown. Here we report that
      Herp regulates autophagy to clear poly-ubiquitin (poly-Ub) protein aggregates.
      Proteasome inhibition and glucose starvation (GS) led to a high level of poly-Ub
      protein aggregation that was drastically reduced by stably knocking down Herp
      (shHerp cells). The enhanced removal of poly-Ub inclusions protected cells from
      death caused by glucose starvation. Under basal conditions and increasingly after
      stress, higher LC3-II levels and GFP-LC3 puncta were observed in shHerp cells
      compared to control cells. Herp knockout cells displayed basal up-regulation of
      two essential autophagy regulators-Atg5 and Beclin-1, leading to increased
      autophagic flux. Beclin-1 up-regulation was due to a reduction in Hrd1 dependent
      proteasomal degradation, and not at transcriptional level. The consequent higher
      autophagic flux was necessary for the clearance of aggregates and for cell
      survival. We conclude that Herp operates as a relevant factor in the defense
      against glucose starvation by modulating autophagy levels. These data may have
      important implications due to the known up-regulation of Herp in pathological
      states such as brain and heart ischemia, both conditions associated to acute
      nutritional stress. 

PMID- 24120521
TI  - Clinical simulation using deliberate practice in nursing education: a Wilsonian
      concept analysis.
AB  - Effective use of simulation is dependent on a complete understanding of
      simulation's central conceptual elements. Deliberate practice, a constituent of
      Ericsson's theory of expertise, has been identified as a central concept in
      effective simulation learning. Deliberate practice is compatible with simulation
      frameworks already being suggested for use in nursing education. This paper uses
      Wilson's Method of concept analysis for the purpose of exploring the concept of
      deliberate practice in the context of clinical simulation in nursing education.
      Nursing education should move forward in a manner that reflects best practice in
      nursing education.

PMID- 24120522
TI  - Effect of varying dietary levels of LC-PUFA and vegetable oil sources on
      performance and fatty acids of Senegalese sole post larvae: puzzling results
      suggest complete biosynthesis pathway from C18 PUFA to DHA.
AB  - Lipid nutrition of marine fish larvae has focused on supplying essential fatty
      acids (EFA) at high levels to meet requirements for survival, growth and
      development. However, some deleterious effects have been reported suggesting that
      excessive supply of EFA might result in insufficient supply of energy substrates,
      particularly in species with lower EFA requirements such as Senegalese sole
      (Solea senegalensis). This study addressed how the balance between EFA and non
      EFA (better energy sources) affects larval performance, body composition and
      metabolism and retention of DHA, by formulating enrichment emulsions containing
      two different vegetable oil sources (olive oil or soybean oil) and three DHA
      levels. DHA positively affected growth and survival, independent of oil source,
      confirming that for sole post-larvae it is advantageous to base enrichments on
      vegetable oils supplying higher levels of energy, and supplement these with a DHA
      rich oil. In addition, body DHA levels were generally comparable considering the
      large differences in their dietary supply, suggesting that the previously
      reported ?4 fatty acyl desaturase (fad) operates in vivo and that DHA was
      synthesized at physiologically significant rates through a mechanism involving
      transcriptional up-regulation of ?4fad, which was significantly up-regulated in
      the low DHA treatments. Furthermore, data suggested that DHA biosynthesis may be
      regulated by an interaction between dietary n-3 and n-6 PUFA, as well as by
      levels of LC-PUFA, and this may, under certain nutritional conditions, lead to
      DHA production from C18 precursors. The molecular basis of putative fatty acyl ?5
      and ?6 desaturation activities remains to be fully determined as thorough
      searches have found only a single (?4) Fads2-type transcript. Therefore, further
      studies are required but this might represent a unique activity described within
      vertebrate fads. 

PMID- 24120523
TI  - Indirect restorations for severe tooth wear: fracture risk and layer thickness.
AB  - OBJECTIVES: This in vitro study investigated static failure risk related to
      restoration layer thickness for different indirect materials and compare them to
      direct composites. METHODS: Two ceramics (IPS e-max CAD, EmpressCAD (Ivoclar
      Vivadent)), two indirect composites (Estenia (Kuraray), Sinfony (3M)) and two
      direct composites (Clearfil AP-X (Kuraray), Tetric EvoCeram (Ivoclar Vivadent))
      were chosen. Of each material, 25 discs varying in thickness (0.5-3.0mm) were
      prepared and cemented to bovine dentine. For measuring compressive strength,
      samples were placed in a universal testing device. Each sample was uniaxially
      loaded until failure occurred. For each material a regression model based on the
      Weibull distribution was used to estimate the relation between restoration layer
      thickness and failure. Using these models, the chance of failure, standard error
      and 95% confidence interval for that chance is estimated. Groups of materials
      were compared as well. RESULTS: Except for Tetric Evoceram, all materials show a
      significant positive association between layer-thickness and compressive
      strength, with an increased strength of increased thickness. ProCAD performed
      significantly worse than all other materials, especially when compared to the
      other ceramic material (IPS e-max CAD) (p=0.001). CONCLUSION: For most tested
      materials, a thicker layer offers more strength, however, this property seems to
      be material/brand specific. CLINICAL RELEVANCE: As direct composites showed the
      best results within the limitations of this in vitro study, dentists should
      consider these materials as a good choice for restoring severe tooth wear, and
      may offer superior performance compared to indirect composites and ceramics. For
      some brands of materials thicker layers result in a stronger restoration.

PMID- 24120524
TI  - Water channel structures analysed by electron crystallography.
AB  - BACKGROUND: The mechanisms underlying water transport through aquaporin (AQP)
      have been debated for two decades. The water permeation phenomenon of AQP seems
      inexplicable because the Grotthuss mechanism does not allow for simultaneous fast
      water permeability and inhibition of proton transfer through the hydrogen bonds
      of water molecules. SCOPE OF REVIEW: The AQP1 structure determined by electron
      crystallography provided the first insights into the proton exclusion mechanism
      despite fast water permeation. Although several studies have provided clues about
      the mechanism based on the AQP structure, each proposed mechanism remains
      incomplete. The present review is focused on AQP function and structure solved by
      electron crystallography in an attempt to fill the gaps between the findings in
      the absence and presence of lipids. MAJOR CONCLUSIONS: Many AQP structures can be
      superimposed regardless of the determination method. The AQP fold is preserved
      even under conditions lacking lipids, but the water arrangement in the channel
      pore differs. The differences might be explained by dipole moments formed by the
      two short helices in the lipid bilayer. In addition, structure analyses of double
      layered two-dimensional crystals of AQP suggest an array formation and cell
      adhesive function. GENERAL SIGNIFICANCE: Electron crystallography findings not
      only have contributed to resolve some of the water permeation mechanisms, but
      have also elucidated the multiple functions of AQPs in the membrane. The roles of
      AQPs in the brain remain obscure, but their multiple activities might be
      important in the regulation of brain and other biological functions. This article
      is part of a Special Issue entitled Aquaporins.

PMID- 24120525
TI  - Geographic distance is not associated with inferior outcome when using long-term
      transplant clinic strategy.
AB  - The optimal healthcare model for follow-up of allogeneic hematopoietic stem cell
      transplantation (HSCT) recipients after day 100 is not clear. We previously
      demonstrated that longitudinal follow-up at the transplant center using a
      multidisciplinary approach is associated with superior survival. Recent data
      suggest that increased distance from the transplant center is associated with
      inferior survival. A dedicated long-term transplant clinic (LTTC) was established
      in 2006 at our center. We hypothesized that geographic distance would not be
      associated with inferior outcome if patients are followed in the LTTC. We studied
      299 consecutive patients who underwent HSCT and established care in an LTTC. The
      median distance from the transplant center was 118 miles (range, 1 to 1591). The
      75th percentile (170 miles) was used as the cut-off to analyze the impact of
      distance from the center on outcome (219 patients <= 75th percentile; 80 patients
      >75th percentile). The 2 groups were balanced for pretransplant characteristics.
      In multivariate analyses adjusted for donor type, Center for International Blood
      and Marrow Transplant Research risk, and transplant regimen intensity, distance
      from transplant center did not impact outcome. Our study suggests that geographic
      distance from the transplant center is not associated with inferior outcome when
      follow-up care is delivered via a dedicated LTTC incorporating well-coordinated
      multidisciplinary care.

PMID- 24120527
TI  - Proteomics study reveals the molecular mechanisms underlying water stress
      tolerance induced by Piriformospora indica in barley.
AB  - Piriformospora indica is a mutualistic root endophytic fungus, which transfers
      several benefits to hosts including enhance plant growth and increase yield under
      both normal and stress conditions. It has been shown that P. indica root
      colonization enhances water stress tolerance based on general and non-specific
      plant-species mechanism. To better understand the molecular mechanism of P.
      indica-mediated drought stress tolerance, we designed a set of comparative
      experiments to study the impact of P. indica on barely plants cultivar "Golden
      Promise" grown under different drought levels [Filed capacity (F.C.) and 25%
      F.C.]. P. indica enhanced root and shoot biomass of colonized plants under both
      well-watered and water-deficit conditions. Proteome analysis of P. indica
      colonized barley leaves under well-treated and water-deficit conditions resulted
      in detection of 726 reproducibly protein spots. Mass spectrometry analysis
      resulted in the identification of 45 differentially accumulated proteins involved
      in photosynthesis, reactive oxygen scavenging, metabolisms, signal transduction,
      and plant defense responses. Interestingly, P. indica increased the level of
      proteins involved in photosynthesis, antioxidative defense system and energy
      transport. We propose that P. indica-mediated drought stress tolerance in barely
      is through photosynthesis stimulation, energy releasing and enhanced
      antioxidative capacity in colonized plants. BIOLOGICAL SIGNIFICANCE: Plant
      mutualistic symbionts offer long-term abiotic stress tolerance through the host
      adaptation to environmental stress. There have been a few published proteomic
      studies of plant symbionts to drought, and this is thought to be the first
      proteomic analysis, demonstrating the impact of endophyte on barley plant under
      drought stress. For some of identified proteins like TCTP and PCNA, a connection
      to physiological function in plants is novel, and can be the best candidates for
      sources of drought tolerance in future studies.

PMID- 24120526
TI  - Protective effect of cytomegalovirus reactivation on relapse after allogeneic
      hematopoietic cell transplantation in acute myeloid leukemia patients is
      influenced by conditioning regimen.
AB  - Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant
      (allo-HCT) has been associated with a reduced risk of relapse in patients with
      acute myeloid leukemia (AML). However, the influence of the conditioning regimen
      on this protective effect of CMV reactivation after allo-HCT is relatively
      unexplored. To address this, we evaluated the risk of relapse in 264 AML patients
      who received T cell-replete, 6/6 HLA matched sibling or 10/10 HLA matched
      unrelated donor transplantation at a single institution between 2006 and 2011. Of
      these 264 patients, 206 received myeloablative (MA) and 58 received reduced
      intensity conditioning (RIC) regimens. CMV reactivation was observed in 88
      patients with MA conditioning and 37 patients with RIC. At a median follow-up of
      299 days, CMV reactivation was associated with significantly lower risk of
      relapse in patients who received MA conditioning both in univariate (P = .01) and
      multivariate analyses (hazard ratio, .5246; P = .006); however, CMV reactivation
      did not significantly affect the risk of relapse in our RIC cohort. These results
      confirm the protective effect of CMV reactivation on relapse in AML patients
      after allo-HCT reported by previous studies but suggest this protective effect of
      CMV reactivation on relapse is influenced by the conditioning regimen used with
      the transplant.

PMID- 24120528
TI  - Subunit-specific mass spectrometry method identifies haptoglobin subunit alpha as
      a diagnostic marker in non-small cell lung cancer.
AB  - Haptoglobin (Hp) subunits have been suggested as a potential serum marker for
      lung cancer. Research is intense on the application of Hp subunits to predict the
      cancer earlier. Nevertheless, it remains difficult to accurately measure the
      content of Hp subunits. We developed stable isotope dilution-multiple reaction
      monitoring mass spectrometry (SID-MRM-MS) capable of measuring Hp subunits (alpha
      and beta chains). Three isotopic analogs (NPANPVQ, TEGDGVYTLNDK and ILGGHLDAK for
      alpha, alpha2 and beta chain, respectively) were used as internal standard (IS)
      for SID-MRM-MS. Serum levels of each Hp subunit were measured in 210 clinical
      samples using SID-MRM-MS. A concentration ratio of each Hp subunit to total Hp
      was investigated. Secretion levels of alpha and beta chains were significantly
      increased in non-small cell lung cancer (NSCLC) compared to controls (P<0.0001).
      Alterations of the alpha chain ratio were more apparent than beta chain between
      controls and NSCLC (P=0.0001 and 0.338 for alpha and beta chains, respectively).
      In conclusion, this study provides not only an efficient quantitative method to
      determine each Hp subunit in crude sera, but also evidence that Hp alpha chain is
      a more prospective biomarker to diagnose NSCLC than beta chain. BIOLOGICAL
      SIGNIFICANCE: Recent several studies have reported Hp as a potential biomarker
      for diagnosis of lung cancer. However a successful evaluation of the value of Hp
      subunits was not achieved on clinical samples. To evaluate the diagnostic
      performance of each Hp subunit, the development of an accurate quantitative assay
      of Hp subunits is necessary. In this regard, we employed a new analytical method
      using stable isotope dilution-multiple reaction monitoring mass spectrometry (SID
      MRM-MS), capable of measuring Hp subunits in 210 clinical specimens. In this
      article, we measured the Hp subunit concentrations and Hp subunits/total Hp
      ratios in patients with NSCLC using SID-MRM-MS. This is the first report on the
      evaluation of each Hp subunit as a lung cancer marker using SID-MRM-MS.
      Consequently, we evaluated specific three tryptic peptides (e.g. NPANPVQ,
      TEGDGVYTLNDK and ILGGHLDAK for alpha, alpha2 and beta chain, respectively) with
      high specificity and sensitivity for determination of Hp subunits. Through future
      large prospective cohort studies, the clinical application of Hp subunits as
      complementary markers, especially Hp alpha, would be useful for the diagnosis of
      NSCLC.

PMID- 24120529
TI  - Carbon acquisition and accumulation in microalgae Chlamydomonas: Insights from
      "omics" approaches.
AB  - Understanding the processes and mechanisms of carbon acquisition and accumulation
      in microalgae is fundamental to enhance the cellular capabilities aimed to
      environmental and industrial applications. The "omics" approaches have greatly
      contributed to expanding the knowledge on these carbon-related cellular
      responses, reporting large data sets on microalgae transcriptome, proteome and
      metabolome. This review emphasizes the advances made on Chlamydomonas
      exploration; however, some knowledge acquired from studying this model organism,
      may be extrapolated to close algae species. The large data sets available for
      this organism revealed the identity of a vast range of genes and proteins which
      are integrating carbon-related mechanisms. Nevertheless, these data sets have
      also highlighted the need for integrative analysis in order to fully explore the
      information enclosed. Here, some of the main results from "omics" approaches
      which may contribute to the understanding of carbon acquisition and accumulation
      in Chlamydomonas were reviewed and possible applications were discussed.
      BIOLOGICAL SIGNIFICANCE: A number of important publications in the field of
      "omics" technologies have been published reporting studies of the model green
      microalga Chlamydomonas reinhardtii and related to microalgal biomass production.
      However, there are only few attempts to integrate these data. Publications
      showing the results from "omics" approaches, such as transcriptome, metabolome
      and proteome, focused in the study of mechanisms of carbon acquisition and
      accumulation in microalgae were reviewed. This review contributes to highlight
      the knowledge recently generated on such "omics" studies and it discusses how
      these results may be important for the advance of applied sciences, such as
      microalgae biotechnology.

PMID- 24120530
TI  - Proteomic alterations induced by ionic liquids in Aspergillus nidulans and
      Neurospora crassa.
AB  - This study constitutes the first attempt to understand at the proteomic level the
      fungal response to ionic liquid stress. Ascomycota are able to grow in media
      supplemented with high concentrations of an ionic liquid, which, in turn, lead to
      major alterations in the fungal metabolic footprint. Herein, we analysed the
      differential accumulation of mycelial proteins in Aspergillus nidulans and
      Neurospora crassa after their exposure to two of the most commonly used ionic
      liquids: 1-ethyl-3-methylimidazolium chloride or cholinium chloride. Data
      obtained showed that numerous stress-responsive proteins (e.g. anti-ROS defence
      proteins) as well as several critical biological processes and/or pathways were
      affected by either ionic liquid. Amongst other changes, these compounds altered
      developmental programmes in both fungi (e.g. promoting the development of Hulle
      cells or conidiation) and led to accumulation of osmolytes, some of which may
      play an important role in multiple stress responses. In particular, in N. crassa,
      both ionic liquids increased the levels of proteins which are likely involved in
      the biosynthesis of unusual metabolites. These data potentially open new
      perspectives on ionic liquid research, furthering their conscious design and
      their use to trigger production of targeted metabolites. BIOLOGICAL SIGNIFICANCE:
      The present study emphasises the importance of understanding ionic liquid's
      stress responses, crucial to further their safe large-scale usage. Knowledge of
      the alterations prompted at a cellular and biochemical level gives also fresh
      perspectives on how to employ these "novel" compounds to manipulate proteins or
      pathways of biotechnological value. The results presented here provide meaningful
      insights into the understanding of fungi stress and adaptation responses to
      anthropogenic chemicals used in industry.

PMID- 24120531
TI  - Conserved Asf1-importin beta physical interaction in growth and sexual
      development in the ciliate Tetrahymena thermophila.
AB  - How the eukaryotic cell specifies distinct chromatin domains is a central problem
      in molecular biology. The ciliate protozoan Tetrahymena thermophila features a
      separation of structurally and functionally distinct germ-line and somatic
      chromatin into two distinct nuclei, the micronucleus (MIC) and macronucleus (MAC)
      respectively. To address questions about how distinct chromatin states are
      assembled in the MAC and MIC, we have initiated studies to define protein-protein
      interactions for T. thermophila chromatin-related proteins. Affinity purification
      followed by mass spectrometry analysis of the conserved Asf1 histone chaperone in
      T. thermophila revealed that it forms a complex with an importin beta, ImpB6.
      Furthermore, these proteins co-localized to both the MAC and MIC in growth and
      development. We suggest that newly synthesized histones H3 and H4 in T.
      thermophila are transported via Asf1-ImpB6 in an evolutionarily conserved pathway
      to both nuclei where they then enter nucleus-specific chromatin assembly
      pathways. These studies set the stage for further use of functional proteomics to
      elucidate details of the characterization and functional analysis of the unique
      chromatin domains in T. thermophila. BIOLOGICAL SIGNIFICANCE: Asf1 is an
      evolutionarily conserved chaperone of H3 and H4 histones that functions in
      replication dependent and independent chromatin assembly. Although Asf1 has been
      well studied in humans and yeast (members of the Opisthokonta lineage of
      eukaryotes), questions remain concerning its mechanism of function. To obtain
      additional insight into the Asf1 function we have initiated a proteomic analysis
      in the ciliate protozoan T. thermophila, a member of the Alveolata lineage of
      eukaryotes. Our results suggest that an evolutionarily conserved function of Asf1
      is mediating the nuclear transport of newly synthesized histones H3 and H4.

PMID- 24120532
TI  - Germination of salt-stressed seeds as related to the ethylene biosynthesis
      ability in three Stylosanthes species.
AB  - Stylosanthes, a genus of tropical forage legume, is known to exhibit good
      persistence in saline soils, yet mechanisms for regulation of seed germination
      under salt stress are poorly understood. This study was carried out to evaluate
      the mode of action of salt stress on seed germination of Stylosanthes. 1
      Aminocyclopropane-1-carboxylic acid (ACC) increased ethylene biosynthesis and
      germination of NaCl-inhibited seeds in a dose-dependent manner. Contents of ACC
      and germination of Stylosanthes humilis seeds increased following transfer from
      NaCl solution to deionised water, but not after transfer to l-alpha-(2
      aminoethoxyvinyl)-glycine (AVG) solution, an inhibitor of ethylene biosynthesis.
      Ethylene biosynthesis was much larger in NaCl-treated seeds of Stylosanthes
      guianensis than in seeds of S. humilis and Stylosanthes capitata, a fact which
      was reflected in higher germination rates. S. guianensis seedlings also displayed
      higher growth and survival rates than S. humilis and S. capitata under salt
      stress. Moreover, smaller ACC levels, as well as reduced ethylene biosynthesis of
      S. capitata seeds were accompanied by lower germination under salt stress. In
      addition, S. capitata seedlings treated with NaCl solutions exhibited relatively
      lower growth and survival rates in comparison with S. humilis and S. guianensis.
      Thus, different abilities to synthesize ethylene by S. guianensis, S. humilis and
      S. capitata seeds explain the differences in tolerance to salt stress of the
      three species. 

PMID- 24120533
TI  - Responses of cyclic phosphorylation of MAPK-like proteins in intertidal
      macroalgae after environmental stress.
AB  - The presence and activation of MAPK-like proteins in intertidal macroalgae is
      described in the current study. Two MAPK-like proteins of 40 and 42 kDa in size
      similar to p38 and JNK, of mammalian cells have been identified in six
      representative species of intertidal macroalgae from the Strait of Gibraltar
      (Southern Spain), namely in the chlorophytes Ulva rigida and Chaetomorpha aerea,
      the rhodophytes Corallina elongata and Jania rubens, and the phaeophytes Dictyota
      dichotoma and Dilophus spiralis. Phosphorylation of MAPK-like proteins was
      studied during semi-tidal cycles. Analysis of p38-like and JNK-like MAPKs in
      macroalgae protein extracts was carried out by using specific antibodies against
      the phosphorylated forms of both MAPKs. Protein blot analysis of samples
      collected from 2009 to 2011 in natural growing sites on days when either low or
      high tide occurred at midday, indicated that MAPK-like proteins in all species
      were highly phosphorylated in response to desiccation imposed by low tide or high
      irradiance. Phosphorylation of p38-like MAPK always preceded that of JNK-like
      MAPK. In addition, phosphorylation of MAPKs was fastest in rhodophytes, followed
      by chlorophytes and then finally phaeophytes. In the first group, phosphorylation
      was mostly dependent on desiccation, whereas both high irradiance and desiccation
      were responsible for p38-like and JNK-like phosphorylation in chlorophytes. In
      phaeophytes, high irradiance was mostly responsible for MAPK-like activation.

PMID- 24120534
TI  - Expression patterns and regulation of SlCRF3 and SlCRF5 in response to cytokinin
      and abiotic stresses in tomato (Solanum lycopersicum).
AB  - Cytokinin is an influential hormone involved in numerous aspects of plant growth
      and development. A group of transcription factors-cytokinin response factors
      (CRFs) has been included as a side branch to cytokinin signaling pathway which
      also constitute a subset of the AP2/ERF family of transcription factor proteins.
      This study examined the expression patterns of two transcription factor genes
      SlCRF3 and SlCRF5 in tomato (Solanum lycopersicum) to determine their regulation
      in response to cytokinin and a variety of abiotic stress conditions. Analyses
      conducted during different developmental stages by RT-PCR or GUS reporter gene
      expression revealed that these genes are differentially expressed in vegetative
      and reproductive organs. qRT-PCR experiments were also performed to study
      regulation by the hormone cytokinin and abiotic stress conditions such as
      flooding, drought, osmotic, oxidative, and temperature. These showed that SlCRF3
      and SlCRF5 have different patterns of regulation in leaf, stem, and roots with
      SlCRF5 showing greater induction in leaf or root tissue compared to SlCRF3 in
      most cases. Additionally, knockdown analysis for SlCRF5 revealed defects across
      development including leaf morphology, primary root growth, and lateral root
      formation. Together, these findings indicate that SlCRF3 and SlCRF5 are potential
      regulators of tomato developmental processes associated with cytokinin or abiotic
      stresses. 

PMID- 24120535
TI  - Epidemiology of enterovirus 71 infections in Taiwan.
AB  - Enterovirus 71 (EV71) was first described in USA in 1969 but retrospective
      studies in The Netherlands further detected EV71 in the clinical specimens
      collected in 1963. EV71 has one single serotype measured by using hyperimmune
      animal antisera but can be phylogenetically classified into three genogroups (A,
      B, and C) including 11 genotypes (A, B1-B5, C1-C5). In Taiwan, EV71 caused a
      large-scale nationwide epidemic in 1998. Retrospective studies further detected
      EV71 in clinical specimens collected from hand-foot-mouth disease patients in
      1980 and 1986. Therefore, EV71 may have circulated in Taiwan prior to 1980. Since
      1998, EV71 has cyclically caused nationwide epidemics with different predominant
      genotypes in 1998 (genotype C2), 2000-2001 (B4), 2005 (C4), 2008 (B5), and 2012
      (B5). Phylogenetic analysis revealed that C4 viruses isolated in 2005 were
      probably from China, B5 viruses isolated in 2008 were probably from South Eastern
      Asia, and B5 viruses isolated in 2012 were probably from Xiamen, China. Several
      studies have collected postinfection sera from children to measure cross-reactive
      neutralizing antibody titers against different EV71 genotypes and found that
      antigenic differences between genogroup B and C viruses did not have a clear
      pattern but that genotype A virus was antigenically different from genogroup B
      and C viruses. In conclusion, EV71 cyclically caused nationwide epidemics through
      international importations. EV71 surveillance in Taiwan should combine genetic
      and serological methods. 

PMID- 24120536
TI  - Epidemiological features of Kawasaki disease in Taiwan, 1976-2007: results of
      five nationwide questionnaire hospital surveys.
AB  - BACKGROUND: Kawasaki disease (KD) affects mainly children younger than 5 years of
      age, leading to coronary artery lesions, and even to life-threatening myocardial
      infarction. In Taiwan, KD was encountered for the first time in 1976; then, it
      continued to occur in increasing numbers. METHODS: For the survey of
      epidemiological features of KD in Taiwan, we conducted five nationwide
      questionnaire hospital surveys in 1987, 1992, 1994, 2001, and 2008, respectively.
      In each survey, a special questionnaire form, together with a request letter and
      diagnostic guidelines for KD, was sent to the chairman of the Department of
      Pediatrics of all hospitals with 100 or more beds in Taiwan. RESULTS: KD patients
      increased to a total of 14,399 patients by 2007, with the highest number of 1018
      in 2001, and the highest incidence of 66.24 per 100,000 children < 5 years of age
      in 2006. Of the 14,399 patients, the male-to-female ratio ranged from 1.5 to 1.7.
      Of these patients, 57.6-65.2% were < 2 years of age, 23.3-26.6% were 2-4 years of
      age, and 11.4-15.8% were >= 5 years of age. Coronary artery lesions were noted in
      20.2-31.5% of patients. Fourteen cases expired, documenting that the fatality
      rate decreased from 0.4% to 0.03% during the 31 years from 1976 to 2007.
      CONCLUSION: In Taiwan, KD was encountered for the first time in 1976, and it
      continued to occur, reaching the highest annual incidence of 66.24 per 100,000
      children < 5 years of age in 2006. In Taiwan, the first emergence of KD came in
      1976; the annual increment of the incidence rate was lower (2.41 in Taiwan vs.
      4.17 Japan), and no significant KD outbreak was observed in Taiwan.

PMID- 24120537
TI  - Proton-decoupled CPMG: a better experiment for measuring (15)N R2 relaxation in
      disordered proteins.
AB  - (15)N R2 relaxation is one of the most informative experiments for
      characterization of intrinsically disordered proteins (IDPs). Small changes in
      nitrogen R2 rates are often used to determine how IDPs respond to various
      biologically relevant perturbations such as point mutations, posttranslational
      modifications and weak ligand interactions. However collecting high-quality (15)N
      relaxation data can be difficult. Of necessity, the samples of IDPs are often
      prepared with low protein concentration and the measurement time can be limited
      because of rapid sample degradation. Furthermore, due to hardware limitations
      standard experiments such as (15)N spin-lock and CPMG can sample the relaxation
      decay only to ca. 150ms. This is much shorter than (15)N T2 times in disordered
      proteins at or near physiological temperature. As a result, the sampling of
      relaxation decay profiles in these experiments is suboptimal, which further
      lowers the precision of the measurements. Here we report a new implementation of
      the proton-decoupled (PD) CPMG experiment which allows one to sample (15)N R2
      relaxation decay up to ca. 0.5-1s. The new experiment has been validated through
      comparison with the well-established spin-lock measurement. Using dilute samples
      of denatured ubiquitin, we have demonstrated that PD-CPMG produces up to 3-fold
      improvement in the precision of the data. It is expected that for intrinsically
      disordered proteins the gains may be even more substantial. We have also shown
      that this sequence has a number of favorable properties: (i) the spectra are
      recorded with narrow linewidth in nitrogen dimension; (ii) (15)N offset
      correction is small and easy to calculate; (iii) the experiment is immune to
      various spurious effects arising from solvent exchange; (iv) the results are
      stable with respect to pulse miscalibration and rf field inhomogeneity; (v) with
      minimal change, the pulse sequence can also be used to measure R2 relaxation of
      (15)N(epsilon) spins in arginine side chains. We anticipate that the new
      experiment will be a valuable addition to the NMR toolbox for studies of IDPs. 

PMID- 24120538
TI  - Synthesis and biological evaluation of novel formyl-pyrazoles bearing coumarin
      moiety as potent antimicrobial and antioxidant agents.
AB  - A series of coumarin appended formyl-pyrazoles 14-18 were synthesized by a simple
      and accessible approach. The reaction of 8-acetyl-4-methyl-7-hydroxy coumarin 3
      and phenyl hydrazine hydrochlorides 4-8 produces the intermediate compounds 8
      acetyl-4-methyl-7-hydroxy coumarin hydrazones 9-13. The reaction of compounds 9
      13 and DMF in the presence of POCl3 yielded formyl-pyrazoles bearing coumarin
      moiety 14-18 in good yield. The synthesized new compounds 14-18 and the
      intermediates 8-acetyl-4-methyl-7-hydroxy coumarin hydrazones 9-13 prepared were
      screened in vitro for their antibacterial, antifungal antioxidant activities. The
      compounds 12 and 17 having chloro substitution exhibited promising antifungal and
      antibacterial activity against the different organisms tested. The compound 17
      showed remarkable DPPH radical scavenging ability. 

PMID- 24120539
TI  - Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14alpha-demethylase as
      anti-Chagas disease agents.
AB  - New dialkylimidazole based sterol 14alpha-demethylase inhibitors were prepared
      and tested as potential anti-Trypanosoma cruzi agents. Previous studies had
      identified compound 2 as the most potent and selective inhibitor against parasite
      cultures. In addition, animal studies had demonstrated that compound 2 is highly
      efficacious in the acute model of the disease. However, compound 2 has a high
      molecular weight and high hydrophobicity, issues addressed here. Systematic
      modifications were carried out at four positions on the scaffold and several
      inhibitors were identified which are highly potent (EC50 <1 nM) against T. cruzi
      in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent
      activity against T. cruzi amastigotes, with reduced molecular weight and
      lipophilicity, and exhibit suitable physicochemical properties for an oral drug
      candidate.

PMID- 24120540
TI  - Identification of 2-aminooxazole amides as acyl-CoA: diacylglycerol
      acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy.
AB  - A scaffold hopping strategy was successfully applied in discovering 2
      aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia.
      Further optimization in potency and PK properties resulted in a lead series with
      oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay. 

PMID- 24120542
TI  - The optimization of aminooxadiazoles as orally active inhibitors of Cdc7.
AB  - A series of aminooxadiazoles was optimized for inhibition of Cdc7. Early lead
      isoquinoline 1 suffered from modest cell potency (cellular IC50=0.71 MUM
      measuring pMCM2), low selectivity against structurally related kinases, and high
      IV clearance in rats (CL=18 L/h/kg). Extensive optimization resulted in azaindole
      26 (Cdc7 IC50=1.1 nM, pMCM2 IC50=32 nM) that demonstrated robust lowering of
      pMCM2 in a mouse pharmacodynamic (PD) model when dosed orally. Modifications to
      improve the pharmacokinetic profile of this series were guided by trapping
      experiments with glutathione in rat hepatocytes.

PMID- 24120541
TI  - Synthesis, structure analysis, antitumor evaluation and 3D-QSAR studies of 3,6
      disubstituted-dihydro-1,2,4,5-tetrazine derivatives.
AB  - 3,6-Diaryl-dihydro-1,2,4,5-tetrazine derivatives were synthesized and their
      structures were confirmed by single-crystal X-ray diffraction. Monosubstituted
      dihydrotetrazines are the 1,4-dihydro structure, but disubstituted
      dihydrotetrazines are the 1,2-dihydro structure. The results of further research
      indicated there may be a rearrangement during the synthesis process of
      disubstituted dihydrotetrazines. Their antitumor activities were evaluated
      against A-549 and P388 cells in vitro. The results showed several compounds to be
      endowed with cytotoxicity in the low micromolar range. Two compounds were highly
      effective against A-549 cell and IC50 values were 0.575 and 2.08 MUM,
      respectively. Three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies of comparative molecular field analysis (CoMFA) and comparative
      molecular similarity indices analysis (CoMSIA) were carried out on 37 1,2,4,5
      tetrazine derivatives with antitumor activity against A-549 cell. Models with
      good predictive abilities were generated with the cross validated q(2) values for
      CoMFA and CoMSIA being 0.744 and 0.757, respectively. Conventional r(2) values
      were 0.978 and 0.988, respectively, the predicted R(2) values were 0.916 and
      0.898, respectively. The results provide the tool for guiding the design and
      synthesis of novel and more potent tetrazine derivatives.

PMID- 24120543
TI  - Improved inhibitory activities against tumor-cell migration and invasion by 15
      benzylidene substitution derivatives of andrographolide.
AB  - In the present study, andrographolide (Andro, 1) derivatives were screened to
      identify potent inhibitors against tumor-cell migration and invasion, and
      associated structure-activity relationships were studied. Compared to 1,
      compounds 8a-8d exhibited more potent activities against migration in SGC-7901,
      PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell
      migration and invasion were proved to be associated with the down-regulation of
      MMPs. 

PMID- 24120544
TI  - Cytotoxicity in the age of nano: the role of fourth period transition metal oxide
      nanoparticle physicochemical properties.
AB  - A clear understanding of physicochemical factors governing nanoparticle toxicity
      is still in its infancy. We used a systematic approach to delineate
      physicochemical properties of nanoparticles that govern cytotoxicity. The
      cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3,
      Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the
      transition metal oxide. This trend was not cell-type specific, as observed in non
      transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma
      derived cells (A549). Addition of NPs to the cell culture medium did not
      significantly alter pH. Physiochemical properties were assessed to discover the
      determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric
      point) described the surface charge of NPs in cytosolic and lysosomal
      compartments; (2) relative number of available binding sites on the NP surface
      quantified by X-ray photoelectron spectroscopy was used to estimate the
      probability of biomolecular interactions on the particle surface; (3) band-gap
      energy measurements to predict electron abstraction from NPs which might lead to
      oxidative stress and subsequent cell death; and (4) ion dissolution. Our results
      indicate that cytotoxicity is a function of particle surface charge, the relative
      number of available surface binding sites, and metal ion dissolution from NPs.
      These findings provide a physicochemical basis for both risk assessment and the
      design of safer nanomaterials. 

PMID- 24120545
TI  - Investigations on the metabolic stability of cytosolic phospholipase A2alpha
      inhibitors with 1-indolylpropan-2-one structure.
AB  - Cytosolic phospholipase A2alpha (cPLA2alpha) plays a key role in the pathogenesis
      of many inflammatory diseases, such as rheumatoid arthritis, atopic dermatitis
      and Alzheimer's disease. Therefore, inhibition of this enzyme is assumed to
      provide a novel therapeutic option for the treatment of these maladies. In this
      study we investigated the metabolism of the potent cPLA2alpha inhibitors 1-[3-(4
      phenoxyphenoxy)-2-oxopropyl]indole-5-carboxylic acid (1) and 3-isobutanoyl-1-[3
      (4-phenoxyphenoxy)-2-oxopropyl]indole-5-carboxylic acid (2). Incubation of 1 with
      a mixture of human recombinant CYP1A2, 2C8, 2C9, 2C19, 2D6, 3A4 and NADPH
      cytochrome P450 reductase enzymes led to reduction of its keto group and to
      hydroxylation at the terminal phenoxy residue. To identify the enzymes
      responsible for the observed reactions, experiments with isoform inhibitors were
      performed. In rat liver S9 fractions the only metabolite found was the alcohol 3
      formed by the reduction of the keto group of 1. This reaction here was mainly
      catalyzed by cytosolic short-chain dehydrogenases/reductases (cSDR) as shown by
      inhibition experiments with different carbonyl reductase inhibitors. Furthermore,
      the metabolic stability of 2 in mouse brains was studied after
      intracerebroventricular application of this compound into the right brain
      hemispheres of mice. HPLC/MS analyses revealed that 2 is also readily reduced in
      the brain to an inactive alcohol metabolite most likely by carbonyl reductases. 

PMID- 24120546
TI  - HIV-1 vaccine-specific responses induced by Listeria vector vaccines are
      maintained in mice subsequently infected with a model helminth parasite,
      Schistosoma mansoni.
AB  - In areas co-endemic for helminth parasites and HIV/AIDS, infants are often
      administered vaccines prior to infection with immune modulatory helminth
      parasites. Systemic Th2 biasing and immune suppression caused by helminth
      infection reduces cell-mediated responses to vaccines such as tetanus toxoid and
      BCG. Therefore, we asked if infection with helminthes post-vaccination, alters
      already established vaccine induced immune responses. In our model, mice are
      vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime
      boost manner, then infected with the human helminth parasite Schistosoma mansoni.
      This allows us to determine if established vaccine responses are maintained or
      altered after helminth infection. Our second objective asked if helminth
      infection post-vaccination alters the recipient's ability to respond to a second
      boost. Here we compared responses between uninfected mice, schistosome infected
      mice, and infected mice that were given an anthelminthic, which occurred
      coincident with the boost or four weeks prior, as well as comparing to un-boosted
      mice. We report that HIV-1 vaccine-specific responses generated by Listeria
      vector HIV-1 vaccines are maintained following subsequent chronic schistosome
      infection, providing further evidence that Listeria vector vaccines induce potent
      vaccine-specific responses that can withstand helminth infection. We also were
      able to demonstrate that administration of a second Listeria boost, which
      markedly enhanced the immune response, was minimally impacted by schistosome
      infection, or anthelminthic therapy. Surprisingly, we also observed enhanced
      antibody responses to HIV Gag in vaccinated mice subsequently infected with
      schistosomes. 

PMID- 24120547
TI  - Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza
      A (H1N1) vaccines: reports to VAERS.
AB  - BACKGROUND: Hypersensitivity disorders following vaccinations are a cause for
      concern. OBJECTIVE: To determine the type and rate by age, gender, and vaccine
      received for reported hypersensitivity reactions following monovalent 2009
      pandemic influenza A (H1N1) vaccines. DESIGN: A systematic review of reports to
      the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009
      pandemic influenza A (H1N1) vaccines. SETTING/PATIENTS: US Civilian reports
      following vaccine received from October 1, 2009 through May 31, 2010.
      MEASUREMENTS: Age, gender, vaccines received, diagnoses, clinical signs, and
      treatment were reviewed by nurses and physicians with expertise in vaccine
      adverse events. A panel of experts, including seven allergists reviewed complex
      illnesses and those with conflicting evidence for classification of the event.
      RESULTS: Of 1984 reports, 1286 were consistent with immediate hypersensitivity
      disorders and 698 were attributed to anxiety reactions, syncope, or other
      illnesses. The female-to-male ratio was >=4:1 for persons 20-to-59 years of age,
      but approximately equal for children under 10. One hundred eleven reports met
      Brighton Collaboration criteria for anaphylaxis; only one-half received
      epinephrine for initial therapy. The overall rate of reported hypersensitivity
      reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher
      rate for live vaccine. LIMITATIONS: Underreporting, especially of mild events,
      would result in an underestimate of the true rate of immediate hypersensitivity
      reactions. Selective reporting of events in adult females could have resulted in
      higher rates than reported for males. CONCLUSIONS: Adult females may be at higher
      risk of hypersensitivity reactions after influenza vaccination than men. Although
      the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1)
      vaccines was low, all clinics administering vaccines should be familiar with
      treatment guidelines for these adverse events, including the use of intramuscular
      epinephrine early in the course of serious hypersensitivity reactions.

PMID- 24120549
TI  - Determinants influencing self-paid vaccination coverage, in 0-5 years old Polish
      children.
AB  - Immunization is an important and cost-effective public health intervention to
      protect the population from illness. In Poland, in addition to free of charge
      vaccines, listed in the national program on immunization, self-paid vaccinations
      for pneumococcal, meningococcal, rotavirus, varicella, influenza infections and
      combination vaccines are recommended. The study objective was to measure the
      coverage and influencing determinants of self-paid vaccinations in 0-5-year-old
      children seen between June 2009 and January 2010 at 3 randomly selected GP
      practices located in one region in the south-western part of Poland. Parents of
      the children who were seen consecutively were invited to participate and complete
      questionnaires on socio-demographic data and other factors related to paid
      vaccination. The response rate: 93.3%. Among the 308 parents (18-50 years old,
      median 31 years) who agreed to participate, 77.9% (95%CI: 73.0-82.2%) had their
      child vaccinated with at least one paid vaccine. Combination vaccines were most
      commonly chosen (62.3%), followed by a pneumococcal (36.4%), influenza (14.3%),
      meningococcal (13.3%), and rotavirus (12.7%) vaccine. Most parents admitted that
      their decision was based on a healthcare worker's initiative informing them about
      the topic. The multi-variable regression model revealed that parent's factors:
      age>=25 years, high socio-economic status, having one child, and health system
      factor, i.e. practice location were each associated with greater odds of child
      immunization The high cost of a vaccine was associated with more than five times
      lower chance to immunize a child. Observed high coverage rate regarding self-paid
      vaccines among young children was influenced mostly by combination vaccines. As
      the cost of a vaccine was an important barrier for the immunization, the gradual
      introduction of some of currently self-paid vaccines in a national program would
      be of value. Future interventions on self-paid vaccination coverage should be
      more tailored, focusing especially on young parents with low income who have more
      than one child. 

PMID- 24120548
TI  - Distribution of invasive meningococcal B disease in Italian pediatric population:
      implications for vaccination timing.
AB  - Neisseria meningitidis group B (MenB) is a leading cause of meningitis and
      sepsis. A new vaccine has been recently licensed. The aim of the present study
      was to evaluate the epidemiology of MenB disease in pediatric age and define the
      optimal age for vaccination. All patients aged 0-18 years admitted with a
      diagnosis of meningitis or sepsis to the 83 participating Italian pediatric
      hospitals were included in the study. Blood and/or cerebrospinal fluid (CSF)
      samples were tested by Realtime-PCR and/or culture. One hundred and thirty-six
      cases (mean age 5.0 years, median 2.7) of MenB disease were found. Among these,
      96/136 (70.6%) were between 0 and 5 years, 61/136 (44.9%) were between 0 and 2
      years. Among the latter, 39/61 (63.9%) occurred during the first year of life
      with highest incidence between 4 and 8 months. A case-fatality rate of 13.2% was
      found, with 27.8% cases below 12 months. Sepsis lethality was 24.4%. RT-PCR was
      significantly more sensitive than culture: 82 patients were tested at the same
      time by both methods, either in blood or in CSF; MenB was found by RT-PCR in
      blood or CSF in 81/82 cases (98.8%), culture identified 27/82 (32.9%) infections
      (Cohen's Kappa 0.3; McNemar's: p<10-5). The study shows that the highest
      incidence of disease occurs in the first year of age, with a peak between 4 and 8
      months of life; 30% of deaths occur before 12 months. The results suggest that
      the greatest prevention could be obtained starting MenB vaccination in the first
      months of life; a catch-up strategy up to the fifth year of life could be
      considered. Our results also confirm that Realtime PCR is significantly more
      sensitive than culture. In those countries where only isolate positive infections
      are counted as cases, the incidence of MenB infection results highly
      underestimated.

PMID- 24120550
TI  - Safety, immunogenicity and efficacy assessment of HIV immunotherapy in a multi
      centre, double-blind, randomised, Placebo-controlled Phase Ib human trial.
AB  - BACKGROUND: Combination antiretroviral therapy (cART) is the main therapeutic
      management tool for HIV/AIDS. Despite its success in controlling viral load and
      disease progression, cART is expensive, associated with a range of significant
      side effects and depends for its efficacy on the patient's life-long commitment
      to high levels of treatment adherence. Immunotherapeutic agents can provide
      potential solutions to these shortcomings. Here we describe a Phase Ib trial of
      HIV-v, a synthetic immunotherapy that elicits T- and B-cell effector responses
      against HIV infected cells. METHODS: Fifty-nine cART-naive HIV-infected males
      aged 18-50 years with viral load of 5000-500,000 copies/ml and CD4 counts
      >350/MUl were recruited for this multi-centre, randomised, double blind study.
      Volunteers received one low (250 MUg) or high (500 MUg) dose of HIV-v, either
      alone or adjuvanted (ISA-51). Safety, immunogenicity, CD4 count and viral load
      were monitored over 168 Days. RESULTS: HIV-v was well tolerated and the
      adjuvanted formulations elicited IgG responses in up to 75% of volunteers. The
      high adjuvanted dose also elicited cellular responses in 45% of tested
      volunteers. In these responding subjects viral loads were reduced by over 1 log
      (p=0.04) compared to Placebo and non-responders. No changes in CD4 count were
      observed. CONCLUSIONS: HIV-v is safe and can elicit T- and B-cell responses in
      ART-naive HIV patients that significantly reduce viral load. Improved dosing
      regimens and further research on long term efficacy are required, but HIV-v
      appears to have potential as an immunotherapeutic anti-viral agent. Trial
      registered as EudraCT-2009-010593-37 (ClinicalTrials.gov Identifier:
      NCT01071031).

PMID- 24120551
TI  - Testosterone dynamics and psychopathic personality traits independently predict
      antagonistic behavior towards the perceived loser of a competitive interaction.
AB  - Few studies have investigated the influence of changes in testosterone on
      subsequent competitive, antagonistic behavior in humans. Further, little is known
      about the extent to which such effects are moderated by personality traits. Here,
      we collected salivary measures of testosterone before and after a rigged
      competition. After the competition, participants were given the opportunity to
      act antagonistically against the competitor (allocate a low honorarium). We
      hypothesized that changes in testosterone throughout the competition would
      predict antagonistic behavior such that greater increases would be associated
      with the allocation of lower honorariums. Further, we investigated the extent to
      which personality traits related to psychopathy (fearless dominance, FD; self
      centered impulsivity, SCI; and coldheartedness) moderated this relationship. In
      men (n=104), greater increases in testosterone and greater FD were associated
      with more antagonistic behavior, but testosterone concentrations did not interact
      with personality measures. In women (n=97), greater FD and SCI predicted greater
      antagonistic behavior, but there were no significant endocrine predictors or
      interactions with personality measures. In a secondary set of analyses, we found
      no support for the dual-hormone hypothesis that the relationship between baseline
      testosterone concentrations and behavior is moderated by cortisol concentrations.
      Thus, results are consistent with previous findings that in men, situation
      specific testosterone reactivity rather than baseline endocrine function is a
      better predictor of future antagonistic behavior. The results are discussed with
      respect to the Challenge Hypothesis and the Biosocial Model of Status, and the
      possible mechanisms underlying the independent relations of testosterone and
      personality factors with antagonistic behavior.

PMID- 24120553
TI  - Peripheral and spinal activation of cannabinoid receptors by joint mobilization
      alleviates postoperative pain in mice.
AB  - The present study was undertaken to investigate the relative contribution of
      cannabinoid receptors (CBRs) subtypes and to analyze cannabimimetic mechanisms
      involved in the inhibition of anandamide (AEA) and 2-arachidonoyl glycerol
      degradation on the antihyperalgesic effect of ankle joint mobilization (AJM).
      Mice (25-35g) were subjected to plantar incision (PI) and 24h after surgery
      animals received the following treatments, AJM for 9min, AEA (10mg/kg,
      intraperitoneal [i.p.]), WIN 55,212-2 (1.5mg/kg, i.p.), URB937 (0.01-1mg/kg,
      i.p.; a fatty acid amide hydrolase [FAAH] inhibitor) or JZL184 (0.016-16mg/kg,
      i.p.; a monoacylglycerol lipase [MAGL] inhibitor). Withdrawal frequency to
      mechanical stimuli was assessed 24h after PI and at different time intervals
      after treatments. Receptor specificity was investigated using selective CB1R
      (AM281) and CB2R (AM630) antagonists. In addition, the effect of the FAAH and
      MAGL inhibitors on the antihyperalgesic action of AJM was investigated. AJM, AEA,
      WIN 55,212-2, URB937 and JZL184 decreased mechanical hyperalgesia induced by PI.
      The antihyperalgesic effect of AJM was reversed by pretreatment with AM281 given
      by intraperitoneal and intrathecal routes, but not intraplantarly. Additionally,
      intraperitoneal and intraplantar, but not intrathecal administration of AM630
      blocked AJM-induced antihyperalgesia. Interestingly, in mice pretreated with FAAH
      or the MAGL inhibitor the antihyperalgesic effect of AJM was significantly
      longer. This article presents data addressing the CBR mechanisms underlying the
      antihyperalgesic activity of joint mobilization as well as of the endocannabinoid
      catabolic enzyme inhibitors in the mouse postoperative pain model. Joint
      mobilization and these enzymes offer potential targets to treat postoperative
      pain. 

PMID- 24120552
TI  - Continuously delivered ovarian steroids do not alter dendritic spine density or
      morphology in macaque dorsolateral prefrontal cortical neurons.
AB  - Aged ovariectomized (OVX) female monkeys, a model for menopause in humans, show a
      decline in spine density in the dorsolateral prefrontal cortex (dlPFC) and
      diminished performance in cognitive tasks requiring this brain region. Previous
      studies in our laboratory have shown that long-term cyclic treatment with 17beta
      estradiol (E) produces an increase in spine density and in the proportion of
      thinner spines in layer III pyramidal neurons in the dlPFC of both young and aged
      OVX rhesus monkeys. Here we used 3D reconstruction of Lucifer yellow-loaded
      neurons to investigate whether clinically relevant schedules of hormone therapy
      would produce similar changes in prefrontal cortical neuronal morphology as long
      term cyclic E treatment in young female monkeys. We found that continuously
      delivered E, with or without a cyclic progesterone treatment, did not alter spine
      density or morphology in the dlPFC of young adult OVX rhesus monkeys. We also
      found that the increased density of thinner spines evident in the dlPFC 24h after
      E administration in the context of long-term cyclic E therapy is no longer
      detectable 20days after E treatment. When compared with the results of our
      previously published investigations, our results suggest that cyclic fluctuations
      in serum E levels may cause corresponding fluctuations in the density of thin
      spines in the dlPFC. By contrast, continuous administration of E does not support
      sustained increases in thin spine density. Physiological fluctuations in E
      concentration may be necessary to maintain the morphological sensitivity of the
      dlPFC to E. 

PMID- 24120554
TI  - Prefrontal D1 dopamine signaling is necessary for temporal expectation during
      reaction time performance.
AB  - Responses during a simple reaction time task are influenced by temporal
      expectation, or the ability to anticipate when a stimulus occurs in time. Here,
      we test the hypothesis that prefrontal D1 dopamine signaling is necessary for
      temporal expectation during simple reaction time task performance. We depleted
      dopamine projections to the medial prefrontal circuits by infusing 6
      hydroxidopamine, a selective neurotoxin, into the ventral tegmental area (VTA) of
      rats, and studied their performance on a simple reaction time task with two
      delays. VTA dopamine depletion did not change movements or learning of the
      reaction time task. However, VTA dopamine-depleted animals did not develop delay
      dependent speeding of reaction times, suggesting that mesocortical dopamine
      signaling is required for temporal expectation. Next, we manipulated dopamine
      signaling within the medial prefrontal cortex using local pharmacology. We found
      that SCH23390, a D1-type dopamine receptor antagonist, specifically attenuated
      delay-dependent speeding, while sulpiride, a D2-type receptor antagonist, did
      not. These data suggest that prefrontal D1 dopamine signaling is necessary for
      temporal expectation during performance of a simple reaction time task. Our
      findings provide insight into temporal processing of the prefrontal cortex, and
      how dopamine signaling influences prefrontal circuits that guide goal-directed
      behavior. 

PMID- 24120555
TI  - Methylxanthines do not affect rhythmogenic preBotC inspiratory network activity
      but impair bursting of preBotC-driven motoneurons.
AB  - Clinical stimulation of preterm infant breathing with methylxanthines like
      caffeine and theophylline can evoke seizures. It is unknown whether underlying
      neuronal hyperexcitability involves the rhythmogenic inspiratory active pre
      Botzinger complex (preBotC) in the brainstem or preBotC-driven motor networks.
      Inspiratory-related preBotC interneuronal plus spinal (cervical/phrenic) or
      cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en
      bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory
      bursting perturbed inspiratory cervical nerve activity in en bloc models at
      >0.25mM theophylline or caffeine. Rhythm in the exposed preBotC of transected en
      bloc preparations was less perturbed by 10mM theophylline than cervical root
      bursting which was more affected than phrenic nerve activity. In the preBotC of
      slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM
      masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type gamma
      aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in
      slices neither XII nor preBotC rhythm was disrupted. Methylxanthines (2.5-10mM),
      but not blockade of adenosine receptors, phosphodiesterase-4 or the
      sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by
      muscimol-evoked GABAA receptor activation that was associated with a
      hyperpolarization and input resistance decrease silencing preBotC neurons in
      slices. The latter blockers did neither affect preBotC or cranial/spinal motor
      network bursting nor evoke seizure-like activity or mask corresponding
      methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked
      hyperexcitability originates from motor networks, leaving preBotC activity
      largely unaffected, and suggest that GABAA receptors contribute to methylxanthine
      evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory
      XII motoneuron oscillations are of different origin. 

PMID- 24120556
TI  - Visuo-proprioceptive interactions in degenerative cervical spine diseases
      requiring surgery.
AB  - Cervical proprioception plays a key role in postural control, but its specific
      contribution is controversial. Postural impairment was shown in whiplash injuries
      without demonstrating the sole involvement of the cervical spine. The
      consequences of degenerative cervical spine diseases are underreported in posture
      related scientific literature in spite of their high prevalence. No report has
      focused on the two different mechanisms underlying cervicobrachial pain:
      herniated discs and spondylosis. This study aimed to evaluate postural control of
      two groups of patients with degenerative cervical spine diseases with or without
      optokinetic stimulation before and after surgical treatment. Seventeen patients
      with radiculopathy were recruited and divided into two groups according to the
      spondylotic or discal origin of the nerve compression. All patients and a control
      population of 31 healthy individuals underwent a static posturographic test with
      12 recordings; the first four recordings with the head in 0 degrees  position:
      eyes closed, eyes open without optokinetic stimulation, with clockwise and
      counter clockwise optokinetic stimulations. These four sensorial situations were
      repeated with the head rotated 30 degrees  to the left and to the right. Patients
      repeated these 12 recordings 6weeks postoperatively. None of the patients
      reported vertigo or balance disorders before or after surgery. Prior to surgery,
      in the eyes closed condition, the herniated disc group was more stable than the
      spondylosis group. After surgery, the contribution of visual input to postural
      control in a dynamic visual environment was reduced in both cervical spine
      diseases whereas in a stable visual environment visual contribution was reduced
      only in the spondylosis group. The relative importance of visual and
      proprioceptive inputs to postural control varies according to the type of
      pathology and surgery tends to reduce visual contribution mostly in the
      spondylosis group. 

PMID- 24120557
TI  - Monoamines tissue content analysis reveals restricted and site-specific
      correlations in brain regions involved in cognition.
AB  - The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems
      are deeply involved in cognitive processes via their influence on cortical and
      subcortical regions. The widespread distribution of these monoaminergic networks
      is one of the main difficulties in analyzing their functions and interactions. To
      address this complexity, we assessed whether inter-individual differences in
      monoamine tissue contents of various brain areas could provide information about
      their functional relationships. We used a sensitive biochemical approach to map
      endogenous monoamine tissue content in 20 rat brain areas involved in cognition,
      including 10 cortical areas and examined correlations within and between the
      monoaminergic systems. Whereas DA content and its respective metabolite largely
      varied across brain regions, the NA and 5-HT contents were relatively homogenous.
      As expected, the tissue content varied among individuals. Our analyses revealed a
      few specific relationships (10%) between the tissue content of each monoamine in
      paired brain regions and even between monoamines in paired brain regions. The
      tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence
      when looking at a specific brain region. Most correlations found between cortical
      areas were positive while some cortico-subcortical relationships regarding the
      DA, NA and 5-HT tissue contents were negative, in particular for DA content. In
      conclusion, this work provides a useful database of the monoamine tissue content
      in numerous brain regions. It suggests that the regulation of these
      neuromodulatory systems is achieved mainly at the terminals, and that each of
      these systems contributes to the regulation of the other two. 

PMID- 24120558
TI  - Transfer of information by BMI.
AB  - Brain machine interfaces (BMI) have become important in systems neuroscience with
      the goal to restore motor function in paralyzed patients. We assess the current
      ability of BMI devices to move objects. The topics discussed include: (1) the
      bits of information generated by a BMI signal, (2) the limitations of including
      more neurons for generating a BMI signal, (3) the superiority of a BMI signal
      using single cells versus electroencephalography, (4) plasticity and BMI, (5) the
      selection of a neural code for generating BMI, (6) the suppression of body
      movements during BMI, and (7) the role of vision in BMI. We conclude that further
      research on understanding how the brain generates movement is necessary before
      BMI can become a reasonable option for paralyzed patients. 

PMID- 24120559
TI  - Binocular pattern deprivation with delayed onset has impact on motion perception
      in adulthood.
AB  - The quality of motion perception depends on visual input during early
      development. Even 1month of binocular deprivation (BD) from birth impairs motion
      coherence thresholds when tested in kittens; conversely BD with a 1-month delayed
      onset does not impair it (Mitchell et al., 2009). We showed that 6months of BD
      applied from birth induces a selective impairment in a Global Motion Detection
      task, but not in global form perception, when tested in adulthood (Burnat et al.,
      2002, 2005). In these animals cell counts of the retinal motion-sensitive alpha
      ganglion revealed a life-long increase in OFF-type ganglion cell (Burnat et al.,
      2012). Here we examined in adult cats the effect of BD on global motion
      perception using an array of tasks with gradually increasing perceptual
      difficulty. Two conditions of BD were applied: from birth, lasting for 1, 2, 4 or
      6months, and with a delayed onset with first 2months of normal vision followed by
      2months of BD. Cats deprived from birth for a 6-month period had Global Motion
      Detection impaired, as compared to the normal group. Velocity and low contrast
      defined motion processing was impaired when BD was applied exclusively in months
      3-4 of life. The cats deprived from birth for 1 or 2months were not impaired in
      any of the tested motion tasks. Motion coherence thresholds, when tested at the
      end of a long motion training were not affected by BD and did not differ from
      those obtained for the normal group. Impaired extraction of low contrast-defined
      motion signal was found in cats deprived solely in months 3-4 of life.
      Surprisingly, binocular pattern deprivation during the first 2months of life did
      not weaken motion sensitivity, revealing the occurrence of a critical period for
      motion perception later in development than previously suggested. 

PMID- 24120560
TI  - Phylogenetic analysis of the genus Modicella reveals an independent evolutionary
      origin of sporocarp-forming fungi in the Mortierellales.
AB  - Most studies of tissue differentiation and development have focused on animals
      and plants but many fungi form multi-cellular aggregations of spore-bearing
      tissue known as fruiting bodies or sporocarps. The ability to form sporocarps has
      arisen independently in several different evolutionary lineages of fungi.
      Evolutionary relationships of most sporocarp-forming fungi are well known, but
      the enigmatic zygomycete genus Modicella contains two species of sporocarp
      forming fungi for which the phylogenetic affinities have not been explored based
      on molecular data. Species of Modicella have an uncertain trophic mode and have
      alternatively been considered members of the order Endogonales (which contains
      documented species of sporocarp-forming fungi) or the order Mortierellales (which
      contains no previously documented species of sporocarp-forming fungi). In this
      study we perform phylogenetic analyses based on ribosomal DNA of Modicella
      malleola from the Northern Hemisphere and Modicella reniformis from the Southern
      Hemisphere to determine the evolutionary affinities of the genus Modicella. Our
      analyses indicate that Modicella is a monophyletic genus of sporocarp-forming
      fungi nested within the Mortierellales, a group of microfungi with no previously
      documented sporocarp-forming species. Because Modicella is distantly related to
      all other known sporocarp-forming fungi, we infer that this lineage has
      independently evolved the ability form sporocarps. We conclude that the genus
      Modicella should be a high priority for comparative genomics studies to further
      elucidate the process of sporocarp formation in fungi. 

PMID- 24120561
TI  - Growing families in a shrinking world: legal and ethical challenges in cross
      border surrogacy.
AB  - Crossing national borders to have children is a rapidly growing phenomenon,
      fuelled by restrictions on access and technologies in some countries and for some
      patients, by high costs in others, and all generating a burgeoning multibillion
      dollar international industry. Cross-border gestational surrogacy is one form of
      family building that challenges legal, policy and ethical norms between countries
      and puts both intended parents and gestational surrogates at risk, and can leave
      the offspring of these arrangements vulnerable in a variety of ways, including
      parent-child, immigration and citizenship status. The widely varying political,
      religious and legal views amongst countries make line drawing and rule making
      challenging. This article reviews recent court decisions about and explores the
      legal dimensions of cross-border surrogacy.

PMID- 24120562
TI  - Response: aspirin to improve IVF unexplained implantation rates: time for an
      individualized approach.

PMID- 24120563
TI  - Ovarian SAHA syndrome is associated with a more insulin-resistant profile and
      represents an independent risk factor for glucose abnormalities in women with
      polycystic ovary syndrome: a prospective controlled study.
AB  - BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne,
      hirsutism, and androgenetic alopecia. No previous study has examined the
      prevalence of glucose abnormalities in ovarian SAHA and explored whether it may
      be an independent risk factor for glucose abnormalities. OBJECTIVE: In a
      prospective controlled study, we investigated the spectrum of glucose
      abnormalities in ovarian SAHA and explored whether it is associated with a more
      insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of
      polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women
      were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose
      homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA
      prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS
      phenotype. Ovarian SAHA was independently associated with a more insulin
      resistant profile (higher homeostatic model assessment of insulin resistance
      score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA
      indices, and relative hypoadiponectinemia), and represented an independent risk
      factor for glucose abnormalities regardless of anthropometric features, age, and
      PCOS phenotype. LIMITATION: There was no performance of skin biopsies.
      CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an
      earlier diagnosis and surveillance of metabolic abnormalities, especially in
      Mediterranean PCOS population exhibiting a lower prevalence of glucose
      abnormalities.

PMID- 24120564
TI  - Compliance by California tanning facilities with the nation's first statewide ban
      on use before the age of 18 years.
AB  - BACKGROUND: Exposure to indoor tanning, especially at younger ages, is associated
      with increased risk of skin cancer. Even in states with parental consent
      requirements, teenagers used tanning facilities at high rates. In 2011,
      California became the first state to pass a complete ban on indoor tanning by
      those younger than 18 years. OBJECTIVE: We sought to determine whether tanning
      facilities in California were in compliance with the new law. METHODS: In a cross
      sectional study, telephone calls were placed in May 2013 to a statewide random
      sample of tanning facilities by a study investigator indicating that she was 17
      years old. RESULTS: Of 600 advertised indoor tanning facilities, 338 met
      inclusion criteria. A majority of respondents (77%, 95% confidence interval 72%
      81%) told the underage caller that she could not use their ultraviolet tanning
      facility. Most facilities, however, denied any dangers from ultraviolet tanning
      (61%) and made unlawful claims of specific health benefits, including vitamin-D
      production (44%), skin disease treatment (22%), prevention of future sunburns
      (17%), and prevention or treatment of depression (8%). LIMITATIONS: Tanning
      facilities may respond differently to a 17-year-old's request to tan in person
      versus by telephone. CONCLUSION: Given strong evidence linking indoor tanning to
      skin cancer, and the tanning industry's documented history of marketing
      specifically to teenagers, this study suggests that laws banning indoor tanning
      younger than 18 years can meaningfully impact access. Additional enforcement,
      however, may be required to bring about accurate disclosure of risk and prevent
      claims of unproven health benefits.

PMID- 24120565
TI  - Sex differences in cognitive ageing: testing predictions derived from life
      history theory in a dioecious nematode.
AB  - Life-history theory maintains that organisms allocate limited resources to
      different traits to maximize fitness. Learning ability and memory are costly and
      known to trade-off with longevity in invertebrates. However, since the
      relationship between longevity and fitness often differs between the sexes, it is
      likely that sexes will differentially resolve the trade-off between learning and
      longevity. We used an established associative learning paradigm in the dioecious
      nematode Caenorhabditis remanei, which is sexually dimorphic for lifespan, to
      study age-related learning ability in males and females. In particular, we tested
      the hypothesis that females (the shorter-lived sex) show higher learning ability
      than males early in life but senesce faster. Indeed, young females outperformed
      young males in learning a novel association between an odour (butanone) and food
      (bacteria). However, while learning ability and offspring production declined
      rapidly with age in females, males maintained high levels of these traits until
      mid-age. These results not only demonstrate sexual dimorphism in age-related
      learning ability but also suggest that it conforms to predictions derived from
      the life-history theory. 

PMID- 24120566
TI  - Normal reference value of whole blood viscosity (230s(-1)) of old women and
      geographical factors.
AB  - AIM: This paper aims at supplying a scientific basis for standardizing the normal
      reference value of whole blood viscosity (230s(-1)) of Chinese old women.
      METHODS: The research is made to study the relationship between the normal
      reference value of 6707 samples of whole blood viscosity (230s(-1)) of old women
      and seven geographical factors in 70 areas in China. RESULTS: It is found that
      the correlation between geographical factors and the normal reference value of
      whole blood viscosity (230s(-1)) of old women is quite significant (F=30.137,
      P=0.000). According to the normal reference value of old women's whole blood
      viscosity (230s(-1)) and geographical factors, one regression equation is
      inferred by using the method of enter regression analysis: Y=13.47+0.0006383X1
      0.001083X2-0.1379X3-0.05098X4-0.0008578X5-0.06221X6+0.2114X7+/-0.55. In the above
      equation, Y is the reference value of whole blood viscosity (230s(-1)) of old
      women (mPa.s); X1 is the altitude (m); X2 is the annual sunshine duration (h); X3
      is the annual mean air temperature; X4 is the annual mean relative humidity; X5
      is the annual precipitation amount; X6 is the annual range of air temperature; X7
      is the annual mean wind speed (m/s); and 0.55 is the value of the residual
      standard deviations. CONCLUSION: If geographical values are obtained in a certain
      area, the normal reference value of whole blood viscosity (230s(-1)) of old women
      in this area can be obtained by using the regression equation. Furthermore,
      according to the geographical factors, China can be divided into eight regions:
      Northeast China Region, North China Region, Shanxi-Shaanxi-Inner Mongolia Region,
      Middle and lower reaches of the Yangtze River Region, Southeast China Region,
      Northwest China Region, Southwest China Region and Qinghai-Tibet Plateau Region.

PMID- 24120569
TI  - Meeting report: Fourth international meeting on G-quadruplex Nucleic Acids
      (Singapore, July 1-4, 2013).
AB  - The fourth international meeting on G-quadruplex Nucleic Acids was held in the
      Nanyang Technological University (NTU) of Singapore. Over 150 participants
      gathered from more than 25 countries. Over 40 talks and 100 posters summarized
      our current knowledge of these unusual DNA and RNA structures. 

PMID- 24120567
TI  - Immune senescence and cancer in elderly patients: results from an exploratory
      study.
AB  - BACKGROUND: The challenge of immune senescence has never been addressed in
      elderly cancer patients. This study compares the thymic output and peripheral
      blood telomere length in >=70year old cancer patients. PATIENTS AND METHODS:
      Fifty-two elderly cancer patients and 39 age-matched controls without personal
      history of cancer were enrolled. All patients underwent a Comprehensive Geriatric
      Assessment (CGA), from which a multidimensional prognostic index (MPI) score was
      calculated. Peripheral blood samples were studied for naive and recent thymic
      emigrant (RTE) CD4(+) and CD8(+) cells by flow cytometry. T-cell receptor
      rearrangement excision circle (TREC) levels, telomere length and telomerase
      activity in peripheral blood cells were quantified by real-time PCR. RESULTS: The
      percentages of CD8(+) naive and CD8(+) RTE cells and TREC levels were
      significantly lower in cancer patients than in controls (p=0.003, p=0.004,
      p=0.031, respectively). Telomere lengths in peripheral blood cells were
      significantly shorter in cancer patients than in controls (p=0.046) and did not
      correlate with age in patients, whereas it did in controls (r=-0.354, p=0.031).
      Short telomere (<=median)/low TREC (<=median) profile was associated with higher
      risk of cancer (OR=3.68 [95% CI 1.22-11.11]; p=0.021). Neither unfitness on CGA
      nor MPI score were significantly related to thymic output or telomere length in
      either group. CONCLUSIONS: Immune senescence is significantly worse in elderly
      cancer patients than in age-matched controls. The low thymic output and the
      shorter telomeres in peripheral blood cells of cancer patients may reflect a pre
      existing condition which facilitates the onset of malignancies in elderly people.

PMID- 24120568
TI  - Lifespan extension of rotifers by treatment with red algal extracts.
AB  - Aging results from an accumulation of damage to macromolecules inhibiting
      cellular replication, repair, and other necessary functions. Damage may be due to
      environmental stressors such as metal toxicity, oxidative stress caused by
      imperfections in electron transfer reactions, or other metabolic processes. In an
      effort to discover medical treatments that counteract this damage, we initiated a
      search for small molecule drugs from natural sources using life table experiments
      which, through their unbiased approach, present the opportunity to discover first
      in-class molecules. We have identified marine red algae as a source of natural
      products that slow aging of the invertebrate rotifer Brachionus manjavacas.
      Rotifers are a promising model organism for life extension studies as they
      maintain a short, measurable lifespan while also having an extensive literature
      related to aging. Rotifer lifespan was increased 9-14% by exposure to three of a
      total of 200 screened red algal extracts. Bioassay guided fractionation led to
      semi-purified extracts composed primarily of lipids responsible for rotifer life
      extension. The life extending mixture from the red alga Acanthophora spicifera
      contained eicosanoic, octadecanoic, and hexadecanoic acids as well as several
      unidentified unsaturated fatty acids. The life extending effects of these small
      molecule mixtures are not a result of their direct antioxidant capacity; other
      unknown mechanisms of action are likely involved. An understanding of how these
      natural products interact with their molecular targets could lead to selective
      and effective treatments for slowing aging and reducing age related diseases. 

PMID- 24120570
TI  - Transient replication of a hepatitis C virus genotype 1b replicon chimera
      encoding NS5A-5B from genotype 3a.
AB  - Although hepatitis C virus (HCV) is a pathogen of global significance,
      experimental therapies in current clinical development include highly efficacious
      all-oral combinations of HCV direct-acting antivirals (DAAs). If approved for
      use, these new treatment regimens will impact dramatically upon our capacity to
      eradicate HCV in the majority of virus-infected patients. However, recent data
      from late-stage clinical evaluations demonstrated that individuals infected with
      HCV genotype (GT) 3 responded less well to all-oral DAA combinations than
      patients infected with other HCV GTs. In light of these observations, the present
      study sought to expand the number of molecular tools available to investigate
      small molecule-mediated inhibition of HCV GT3 NS5A and NS5B proteins in
      preclinical tissue-culture systems. Accordingly, a novel subgenomic HCV replicon
      chimera was created by utilizing a GT1b backbone modified to produce NS5A and
      NS5B proteins from a consensus sequence generated from HCV GT3a genomic sequences
      deposited online at the European Hepatitis C Virus database. This approach
      avoided the need to isolate and amplify HCV genomes from sera derived from HCV
      infected patients. The replicon chimera, together with a version engineered to
      express NS5A encoding a Y93H mutation, demonstrated levels of replication in
      transient assays robust enough to assess accurate antiviral activities of
      inhibitors representing different HCV DAA classes. Thus, the replicon chimera
      represents a new simple molecular tool suitable for drug discovery programmes
      aimed at investigating, understanding, and improving GT3a activities of HCV DAAs
      targeting NS5A or NS5B. 

PMID- 24120571
TI  - Development of real-time RT-PCR for the detection of low concentrations of Rift
      Valley fever virus.
AB  - In recent years, Madagascar and the Comoros archipelago have been affected by
      epidemics of Rift Valley fever (RVF), however detection of Rift Valley fever
      virus (RVFV) in zebu, sheep and goats during the post epidemic periods was
      frequently unsuccessful. Thus, a highly sensitive real-time RT-PCR assay was
      developed for the detection of RVFV at low viral loads. A new RVF SYBR Green RT
      PCR targeting the M segment was tested on serum from different RVF seronegative
      ruminant species collected from May 2010 to August 2011 in Madagascar and the
      Comoros archipelago and compared with a RVF specific quantitative real time RT
      PCR technique, which is considered as the reference technique. The specificity
      was tested on a wide range of arboviruses or other viruses giving RVF similar
      clinical signs. A total of 38 out of 2756 serum samples tested positive with the
      new RT-PCR, whereas the reference technique only detected 5 out of the 2756. The
      described RT-PCR is an efficient diagnostic tool for the investigation of
      enzootic circulation of the RVF virus. It allows the detection of low viral RNA
      loads adapted for the investigations of reservoirs or specific epidemiological
      situations such as inter-epizootic periods. 

PMID- 24120572
TI  - Aerobic training in persons who have recovered from juvenile dermatomyositis.
AB  - A recent study has shown that 36 persons who had recovered from juvenile
      dermatomyositis (JDM) have on average an 18% decrease in maximal oxygen uptake.
      The objective of this study was to investigate the effect of a 12-week aerobic
      training program in this group, and assess whether aerobic training can normalize
      aerobic capacity to the expected level for age and gender. The patients
      participating in the study, one male and nine females (16-42 years of age), were
      in remission from JDM, defined as no clinical or biochemical evidence of disease
      activity and no medical treatment for 1 year. The patients had a median disease
      duration of 3.4 years (1.4-10.3), a median treatment duration of 2.4 years (0.4
      9.3) and a median duration of remission of 7.0 years (1.2-30.0). Patients trained
      at home on a cycle ergometer for 12 weeks at a heart rate interval corresponding
      to 65% of their maximal oxygen uptake (VO(2max)). VO(2max) and maximal workload
      (W(max)) were determined before and after the 12-week training period through an
      incremental cycling test to exhaustion. The patients served as their own
      controls. Eight patients with JDM in remission completed the 12-week exercise
      program; one patient completed 9 weeks out of the 12-week program and one dropped
      out of the study. Training increased VO(2max) and W(max) by 26% and 30% (P <
      0.001). Creatine kinase (CK) levels were normal pre-training and did not change
      with training, reflecting no muscle damage. We also found that at a given
      workload, heart rate was lowered significantly after the 12-week training period,
      indicating an improvement in cardiovascular fitness. This study shows that 12
      weeks of moderate-intensity aerobic training is an effective and safe method to
      increase oxidative capacity and fitness in persons who have recovered from JDM.
      The results indicate that the low oxidative capacity in JDM patients in remission
      is reversible and can be improved. Thus, we recommend frequent aerobic training
      to be incorporated into supervised physiotherapy sessions in the treatment of JDM
      patients in remission.

PMID- 24120573
TI  - Implementation of Good Clinical Laboratory Practice (GCLP) guidelines within the
      External Quality Assurance Program Oversight Laboratory (EQAPOL).
AB  - The EQAPOL contract was awarded to Duke University to develop and manage global
      proficiency testing programs for flow cytometry-, ELISpot-, and Luminex bead
      based assays (cytokine analytes), as well as create a genetically diverse panel
      of HIV-1 viral cultures to be made available to National Institutes of Health
      (NIH) researchers. As a part of this contract, EQAPOL was required to operate
      under Good Clinical Laboratory Practices (GCLP) that are traditionally used for
      laboratories conducting endpoint assays for human clinical trials. EQAPOL adapted
      these guidelines to the management of proficiency testing programs while
      simultaneously incorporating aspects of ISO/IEC 17043 which are specifically
      designed for external proficiency management. Over the first two years of the
      contract, the EQAPOL Oversight Laboratories received training, developed standard
      operating procedures and quality management practices, implemented strict quality
      control procedures for equipment, reagents, and documentation, and received
      audits from the EQAPOL Central Quality Assurance Unit. GCLP programs, such as
      EQAPOL, strengthen a laboratory's ability to perform critical assays and provide
      quality assessments of future potential vaccines. 

PMID- 24120575
TI  - Long-term biopermanence of ceramides, cholesteryl esters, and ether-linked
      triglycerides with very-long-chain PUFA in the cadmium-damaged testis.
AB  - Cadmium is known to harm rat testis by causing the dose-dependent apoptotic or
      necrotic death of seminiferous epithelium cells. Here we investigated how this
      affects the lipids with long-chain (C18-C22) and very-long-chain (C24-C32)
      polyunsaturated fatty acids (VLCPUFA) typical of spermatogenic and Sertoli cells.
      A severe acute inflammatory reaction resulted from the massive necrotic death of
      these cells two days after a single high (4mg/kg) dose of CdCl2. This led to the
      conversion of most testicular glycerophospholipids to diradylglycerols (DRG) and
      free fatty acids (FFA) and of most sphingomyelins to ceramides (Cer). By day 30
      the testis weight had decreased three-fold. The DRG and FFA had been metabolized
      but, unexpectedly, ceramides persisted. Also slow to disappear were VLCPUFA
      containing triacylglycerols from former germ cells and ether-linked triglycerides
      and cholesteryl esters (CE) from former Sertoli cells. Similar results were
      observed 30 and 45days after administering repeated small non pro-inflammatory
      CdCl2 doses (1mg/kg). At day 30 after both treatments, an amorphous material
      replaced the original seminiferous tubules and the interstitium was populated by
      macrophages. Species of CE and ether-linked triglycerides containing fatty acids
      other than VLCPUFA steadily accumulated in the irreversibly damaged testis, a
      manifestation of the activity of these cells. The long-term permanence of
      original VLCPUFA-containing neutral lipids, especially ceramides, indicates that
      these phagocytes were slow to clear out the acellular material contained in
      seminiferous tubules, pointing to a form of silent chronic inflammation as an
      additional outcome of the multifactorial commotion caused in the testis by
      experimentally administered cadmium. 

PMID- 24120576
TI  - Real-time sample entropy predicts life-saving interventions after the Boston
      Marathon bombing.
AB  - PURPOSE: Identifying patients in need of a life-saving intervention (LSI) during
      a mass casualty event is a priority. We hypothesized that real-time,
      instantaneous sample entropy (SampEn) could predict the need for LSI in the
      Boston Marathon bombing victims. MATERIALS AND METHODS: Severely injured Boston
      Marathon bombing victims (n = 10) had sample entropy (SampEn) recorded upon
      presentation using a continuous 200-beat rolling average in real time. Treating
      clinicians were blinded to real-time results. The correlation between SampEn,
      injury severity, number, and type of LSI was examined. RESULTS: Victims were
      males (60%) with a mean age of 39.1 years. Injuries involved lower extremities
      (50.0%), head and neck (24.2%), or upper extremities (9.7%). Sample entropy
      negatively correlated with Injury Severity Score (r = -0.70; P = .023), number of
      injuries (r = -0.70; P = .026), and the number and need for LSI (r = -0.82; P =
      .004). Sample entropy was reduced under a variety of conditions. (Table see
      text). CONCLUSIONS: Sample entropy strongly correlates with injury severity and
      predicts LSI after blast injuries sustained in the Boston Marathon bombings.
      Sample entropy may be a useful triage tool after blast injury.

PMID- 24120574
TI  - Fatty acid transporters in skin development, function and disease.
AB  - Fatty acids in the epidermis can be incorporated into complex lipids or exist in
      a free form, and they are crucial to proper functions of the epidermis and its
      appendages, such as sebaceous glands. Epidermal fatty acids can be synthesized de
      novo by keratinocytes or taken up from extracutaneous sources in a process that
      likely involves protein transporters. Several proteins that are expressed in the
      epidermis have been proposed to facilitate the uptake of long-chain fatty acids
      (LCFA) in mammalian cells, including fatty acid translocase/CD36, fatty acid
      binding protein, and fatty acid transport protein (FATP)/very long-chain acyl-CoA
      synthetase. In this review, we will discuss the mechanisms by which these
      candidate transporters facilitate the uptake of fatty acids. We will then discuss
      the clinical implications of defects in these transporters and relevant animal
      models, including the FATP4 animal models and ichthyosis prematurity syndrome, a
      congenital ichthyosis caused by FATP4 deficiency. This article is part of a
      Special Issue entitled The Important Role of Lipids in the Epidermis and their
      Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors:
      Kenneth R. Feingold and Peter Elias. 

PMID- 24120577
TI  - A cross-calibration study of the GE-Lunar iDXA and prodigy for the assessment of
      lumbar spine and total hip bone parameters via three statistical methods.
AB  - This study assessed agreement between the GE Lunar iDXA and Prodigy densitometers
      for bone measurements and used 3 statistical methods to derive cross-calibration
      equations: linear regression, the Deming method, and multivariate analysis.
      Compatibility of machines for the measurements of bone mineral density, bone
      mineral content, and bone area also was explored. Eighty-five adults, age: 45.5
      (SD 12.8) years; body mass index: 25.6 (SD 3.7) kg.m(-2) were measured once at
      the lumbar spine: L1-L4 and total hip on each densitometer, within 24 hours. Both
      linear regression and Deming analysis indicated that cross-calibration equations
      were required at the lumbar spine and total hip but not at the femoral neck.
      Multivariate analysis identified femur thickness and femur percent fat as
      predictive variables at the femoral neck and total hip. Bland Altman analysis
      (Prodigy-iDXA) indicated significant positive bone mineral density bias at the
      lumbar spine and femoral neck. Significant bone mineral content biases were
      observed at all 3 sites and bone area biases at both hip sites. These initial
      results suggest there are small significant differences in the bone parameters
      and that all 3 bone parameters should be evaluated when comparing densitometers,
      especially when there are differences in pixel size between the densitometers. 

PMID- 24120578
TI  - Engineering Bacillus subtilis for acetoin production from glucose and xylose
      mixtures.
AB  - As a vital flavor compound, acetoin is extensively used in dairy products and
      drinks industry. In this study, Bacillus subtilis was engineered to metabolize
      glucose and xylose as substrates for acetoin production. Initially, gene araE
      from B. subtilis, encoding the xylose transport protein AraE, was placed under
      the control of the constitutive promoter P43 for over-expression. Batch cultures
      showed that 10 g/L xylose was depleted completely in 32 h. Subsequently, genes
      xylA and xylB from Escherichia coli, encoding xylose isomerase and xylulokinase
      respectively, were introduced into B. subtilis, and the recombinant turned out to
      assimilate glucose and xylose without preference. In shake-flask fermentations,
      5.5 g/L acetoin with a yield of 0.70 mol(mol sugar)(-1) was obtained by the
      optimum strain BSUL13 under microaerobic conditions, which offered a metabolic
      engineering strategy on engineering microbe as cell factory for the production of
      high-valued chemicals from renewable resource.

PMID- 24120579
TI  - Bovine besnoitiosis in Switzerland: imported cases and local transmission.
AB  - Bovine besnoitiosis is an economically important disease of cattle, caused by
      Besnoitia besnoiti (Protozoa, Apicomplexa). A considerable spreading of this
      parasitic infection has been observed in Europe in the last ten years, mainly
      related to animal trade. In order to investigate the possibility of B. besnoiti
      being unnoticed introduced and getting established in Switzerland through the
      import of breeding cattle from France, a total of 767 animals (650 cattle
      imported from France and 117 cattle that had contact with B. besnoiti positive
      cattle in Swiss farms) were screened for antibodies against B. besnoiti by both a
      commercial ELISA and by the indirect fluorescent antibody test (IFAT). A total of
      101 (13.17%) samples showed a positive reaction in ELISA (cut-off: percent of
      positivity [PP] >= 15) and 16 (2.09%) samples had IFAT titers >= 1:100. Eight of
      those samples reacted positive in Western blot (WB), corresponding to five
      imported Limousin cattle (two cows and one bull from France and two cows from
      Germany) and to three cattle born in Switzerland (one Limousin heifer born from
      one of the positive German cows, and two adult Braunvieh cows, that had been in
      contact with one of the French cows at a Swiss farm). Seven of those animals were
      subclinically infected and one animal showed only very mild signs. They were
      subsequently slaughtered, and the serological diagnosis could be confirmed by
      real-time PCR and/or histopathology in seven animals. The most frequent parasite
      localizations were the tendons and surrounding connective tissue of the distal
      limbs and the skin of the head region. Furthermore, B. besnoiti could be
      successfully isolated in vitro from one French, one German and one Swiss cattle
      (isolates Bb-IPZ-1-CH, Bb-IPZ-2-CH and Bb-IPZ-3-CH). In the current situation in
      Switzerland, prophylactic and control measures should include a serological
      examination of cattle to be imported from endemic areas and the culling of all
      confirmed positive animals from the herd. The evidence of B. besnoiti infection
      in both imported and locally born cattle shows that the conditions for the
      establishment and dissemination of this parasite in Switzerland seem to be
      adequate.

PMID- 24120580
TI  - Perceptions and motivations of career selection in anesthesiology: do medical
      students want what our specialty needs?

PMID- 24120581
TI  - Poliomyelitis sequels in France and the clinical and social needs of survivors: a
      retrospective study of 200 patients.
AB  - INTRODUCTION: Polio survivors in France are estimated at 50,000. This study aimed
      at describing their needs from their clinical and vocational conditions. METHOD:
      A retrospective study of our physical and rehabilitation medicine (PRM)
      consultation activity. RESULTS: One hundred and fifteen women/85 men, with a mean
      age of 51years+/-14.3 (17 to 82). Paralysis involved only one lower limb in 108
      patients, the two lower limbs in 56 patients and only one upper limb in 4. At the
      time of the first consultation 137 patients had experienced functional worsening.
      The complaints were pain (105 subjects), fatigue (59) and new paresis (58). Only
      25% had retired. Post-polio syndrome criteria were present in 46 subjects (23%).
      Patients who had contracted poliomyelitis in France (56%) differed from the other
      subjects with regard to age (58.4 versus 41.5), professional status and frequency
      of PPS (30.9% versus 12.6%). CONCLUSION: These polio survivors were not
      particularly aged and they had often experienced functional worsening. The
      evolution of their disease shall represent a public health issue over the decades
      to come.

PMID- 24120582
TI  - Diagnosis of myelodysplastic syndromes in individuals heterozygous for mutations
      in the alpha- and beta-globin genes: a reminder for haematologists.

PMID- 24120583
TI  - A new device to relieve venipuncture pain can affect haematology test results.
AB  - BACKGROUND: In vitro diagnostic tests play a key role in patients' management
      (e.g., guiding red blood cell transfusions). The aim of this study was to
      evaluate the impact of an innovative device (Buzzy(r)) which is claimed to be
      able to relieve venipuncture pain by means of cold and vibration. This device was
      applied during collection of venous blood by venipuncture for conventional
      haematology testing. MATERIALS AND METHODS: Blood was drawn from 100 volunteers
      by a single, expert phlebotomist. A vein was located in the left forearm without
      applying a tourniquet but using a subcutaneous tissue transilluminator device, so
      that venous stasis was avoided. Blood samples were collected with a 20G straight
      needle directly into 4 mL K3EDTA vacuum tubes. In sequence, external cold and
      vibration was established by Buzzy(r) on the right forearm -5 cm above the
      venipuncture site- for 1 minute before venipuncture and continued until the end
      of the same procedure already performed in the left forearm. Conventional
      haematological tests were performed using the same instrument (Sysmex(r) XE
      2100D) in all cases. RESULTS: When Buzzy(r) was applied before drawing blood,
      erythrocyte counts and associated parameters (i.e., haemoglobin and haematocrit)
      were higher, whereas platelet number, leucocyte count and differential were
      lower. Statistically and clinically significant differences (P<0.001) were
      observed for erythrocytes, haemoglobin and haematocrit. DISCUSSION: From a
      practical perspective, cold-induced haemoconcentration promotes the efflux of
      water, diffusible ions and low molecular weight molecules from the vessel, thus
      increasing the concentration of other blood analytes at the puncture site. These
      variations may influence test results, especially for erythrocytes, haemoglobin
      and haematocrit. The novel Buzzy(r) device should, therefore, be used with
      caution when collecting blood for conventional haematological testing because of
      the observed bias introduced in some parameters.

PMID- 24120584
TI  - A first bout of thrombotic thrombocytopenic purpura triggered by herpes simplex
      infection in a 45-year-old nulliparous female with Upshaw-Schulman syndrome.

PMID- 24120585
TI  - Improving the management and outcome in haemolytic disease of the foetus and
      newborn.

PMID- 24120586
TI  - Neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and
      newborn and managed with intrauterine transfusion: a service evaluation.
AB  - BACKGROUND: This study, conducted in the tertiary Foetal Medicine Unit at St
      Michael's Hospital, Bristol, was designed to obtain information regarding
      neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and
      newborn and managed by intrauterine transfusion, and to determine whether a
      change in intrauterine transfusion protocol in 2004 had improved safety. The new
      protocol included attendance of two Foetal Medicine Unit consultants, foetal
      sedation and use of the intrahepatic vein as an alternative route to placental
      cord insertion if deemed safer. MATERIALS AND METHODS: Data for pregnancies
      affected by haemolytic disease of the foetus and newborn as a result of
      haemolytic red cell alloimmunisation and managed with intrauterine transfusion at
      St Michael's Hospital between 1999 and 2009 were retrospectively collected using
      local databases, and medical note review. RESULTS: Overall, 256 relevant
      intrauterine transfusions were performed. The median number of intrauterine
      transfusions per pregnancy was two. Ninety-three per cent of the live deliveries
      had 5-minute APGAR scores >=9 and 98% were admitted to a Neonatal Intensive Care
      Unit/Special Care Baby Unit, requiring phototherapy (96%), top-up transfusions
      (44%: 23.2% immediate, 13.4% late, 7.3% both), and exchange transfusion (37%). An
      association was found between increased intrauterine transfusion number and
      reduced phototherapy duration and hospital admission: each additional
      intrauterine transfusion reduced the duration of phototherapy by 16% (95% CI:
      0.72-0.98), and Neonatal Intensive Care Unit/Special Care Baby Unit admission by
      44% (95% CI: 0.48-0.66). Following the change in intrauterine transfusion
      protocol, there was a significant reduction in the number of emergency Caesarean
      sections occurring directly after an intrauterine transfusion (n =5 vs 0; P
      =0.02). The foetal loss rate within 48 hours of an intrauterine transfusion was
      1.9% per pregnancy, or 0.8% per intrauterine transfusion: no losses occurred
      under the new protocol (n =3 vs 0; P = NS). DISCUSSION: Although the majority of
      neonates required admission to a Neonatal Intensive Care Unit/Special Care Baby
      Unit and phototherapy, the medium-term outcomes were positive. Importantly, the
      safety of the intrauterine transfusion procedure has improved significantly since
      the change in protocol.

PMID- 24120587
TI  - The results of nucleic acid testing in remunerated and non-remunerated blood
      donors in Lithuania.
AB  - BACKGROUND: In Lithuania, governmentally covered remuneration for whole blood
      donations prevails. Donors may choose to accept or reject the remuneration. The
      purpose of this study was to compare the rate of nucleic acid testing (NAT)
      discriminatory-positive markers for human immunodeficiency virus-1 (HIV-1),
      hepatitis B virus (HBV) and hepatitis C virus (HCV) in seronegative, first-time
      and repeat, remunerated and non-remunerated donations at the National Blood
      Centre in Lithuania during the period from 2005 to 2010. MATERIALS AND METHODS:
      All seronegative whole blood and blood component donations were individually
      analysed by NAT for HIV-1, HBV and HCV. Only discriminatory-positive NAT were
      classified. The prevalence of discriminatory-positive NAT per 100,000 donations
      in the donor groups and the odds ratios comparing the remunerated and non
      remunerated donations were determined. RESULTS: Significant differences were
      observed for HBV NAT results: 47.42 and 26.29 per 100,000 remunerated first-time
      and repeat donations, respectively, compared to 10.6 and 3.58 per 100,000 non
      remunerated first-time and repeat, seronegative donations, respectively. The
      differences were also significant for HCV NAT results: 47.42 and 51.99 for
      remunerated first-time and repeat donations, respectively, compared to 2.12 and 0
      per 100,000 non-remunerated first-time and repeat, seronegative donations,
      respectively. No seronegative, discriminatory-positive NAT HIV case was found.
      The odds of discriminatory HBV and HCV NAT positive results were statistically
      significantly higher for both first-time and repeat remunerated donations
      compared to first-time and repeat non-remunerated donations. DISCUSSION: First
      time and repeat remunerated seronegative donations were associated with a
      statistically significantly higher prevalence and odds for discriminatory
      positive HBV and HCV NAT results compared to first-time and repeat non
      remunerated donations at the National Blood Centre in Lithuania.

PMID- 24120588
TI  - Haemophilia prophylaxis: a model and future directions in Jordan.

PMID- 24120590
TI  - The Dublin Consensus Statement 2012 on optimised supply of plasma-derived
      medicinal products.

PMID- 24120589
TI  - Autologous re-transfusion drain compared with no drain in total knee
      arthroplasty: a randomised controlled trial.
AB  - BACKGROUND: Post-operative anaemia following total knee arthroplasty is reported
      to impede functional mobility in the early period following surgery, whereas
      allogeneic blood transfusions, used to correct low post-operative haemoglobin
      levels, have concomitant disadvantages. The use of a post-operative autologous
      blood re-transfusion drainage system as well as no drainage system following
      total knee arthroplasty have been shown to reduce peri-operative blood loss and
      allogeneic blood transfusions, compared to the regularly used closed-suction
      drains. No randomised studies have been performed, to the best of our knowledge,
      that indicate the superiority of either method. MATERIALS AND METHODS: An open,
      randomised controlled study was conducted in 115 patients undergoing total knee
      arthroplasty who were randomly allocated to an autotransfusion drain or no
      drainage system. The primary end-point was haemoglobin level on the first post
      operative day. RESULTS: In the autotransfusion group 515 mL (0-1,500 mL) of
      drained blood was re-transfused within the first 6 hours after surgery.
      Haemoglobin levels on the first (11.6 vs 11.0 g/dL), second (11.0 vs 10.3 g/dL)
      and third (10.5 vs 9.8 g/dL) days after surgery were significantly higher in the
      autotransfusion group. Total peri-operative net blood loss (1,576 mL vs 1,837 mL;
      -P=0.03) and allogeneic transfusion rates (10.2% vs 19.6%; P=0.15) were lower in
      the autotransfusion group. There were no differences in pain scores, range of
      motion or adverse events during hospital stay and the first 3 months after
      surgery. DISCUSSION: Compared with no drainage, the use of a post-operative
      autologous blood re-transfusion drainage system following total knee arthroplasty
      results in higher post-operative haemoglobin levels and less total blood loss.

PMID- 24120592
TI  - Red blood cell alloimmunisation after platelet transfusion: a 5-year study.

PMID- 24120591
TI  - Hypoxia-inducible factor-1alpha(Pro-582-Ser) polymorphism prevents iron
      deprivation in healthy blood donors.
AB  - BACKGROUND: Frequent blood loss induces progressive depletion of iron stores,
      leading to iron deficiency and, ultimately, to overt iron-deficient anaemia. The
      erythropoietin-mediated bone marrow response to anaemia is under the control of
      hypoxia-inducible factors (HIF), the master regulators of oxygen and iron
      homeostasis. Since the HIF-1alpha(Pro-582-Ser) variant is associated with
      elevated trans-activation capacity of hypoxia responsive elements of target
      genes, we investigated whether the HIF-1alpha(Pro-582-Ser) polymorphism might
      influence the response to repeated blood withdrawals. MATERIALS AND METHODS:
      Using polymerase chain reaction analysis and DNA sequencing, we retrospectively
      investigated the presence of HIF-1alpha(Pro-582-Ser) in a series of 163 blood
      donors. Haematological findings, serum ferritin levels and frequency of donations
      were compared according to the mutational status of the HIF-1alpha gene. RESULTS:
      We found that male carriers of the HIF-1alpha(Pro-582-Ser) polymorphism had
      higher haemoglobin and ferritin levels than individuals homozygous for the wild
      type allele. Moreover, the HIF-1alpha(Pro-582-Ser) polymorphism protected regular
      blood donors from developing iron deficiency and anaemia and predicted
      uninterrupted donation activity. DISCUSSION: These findings show for the first
      time that the HIF-1alpha(Pro-582-Ser) polymorphism significantly affects red
      blood cell and iron homeostasis after blood loss, conferring to male carriers a
      resistance to anaemia. Regarding the female gender, large series of individuals
      should be investigated to establish whether there is an effect of the HIF
      1alpha(Pro-582-Ser) polymorphism in this population. Although these data need to
      be confirmed in prospective studies, they could have important implications in
      blood donor selection and donation procedures.

PMID- 24120593
TI  - Management of notifications of donors with Creutzfeldt-Jakob disease (post
      donation information).

PMID- 24120594
TI  - Transfusion-transmitted hepatitis E in a patient with myelodysplastic syndromes.

PMID- 24120595
TI  - Cost of post-operative intravenous iron therapy in total lower limb arthroplasty:
      a retrospective, matched cohort study.
AB  - BACKGROUND: Requirements for allogeneic red cell transfusion after total lower
      limb arthroplasty are still high (20-50%), and post-operative intravenous iron
      has been shown to reduce transfusion requirements for this surgery. We performed
      a cost analysis to ascertain whether this alternative is also likely to be cost
      effective. MATERIALS AND METHODS: Data from 182 matched-pairs of total lower limb
      arthroplasty patients, managed with a restrictive transfusion protocol and
      without (control group) or with post-operative intravenous iron (iron group),
      were retrospectively reviewed. Acquisition and administration costs of iron (iron
      sucrose or ferric carboxymaltose) and allogeneic red cell concentrates,
      haemoglobin measurements, and prolonged stay in hospital were used for blood
      management cost analysis. RESULTS: Patients in the iron group received 600 mg
      intravenous iron, without clinically relevant incidents, and had a lower
      allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups,
      respectively; p=0.001). The reduction in transfusion rate was more pronounced in
      anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%;
      p=0.011). There were no differences with respect to post-operative infection
      rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9
      days [95% CI: 1.2-2.6]). As intravenous iron reduces the allogeneic transfusion
      rate, both iron formulations were cost-neutral in the different cost scenarios (
      25.5 to 62.1 ?/patient for iron sucrose, and -51.1 to 64.4 ?/patient for ferric
      carboxymaltose). DISCUSSION: In patients presenting with or without pre-operative
      anaemia, post-operative intravenous iron after total lower limb arthroplasty
      seems to be safe and is associated with reduced transfusion rates, without
      incremental costs. For anaemic patients, its efficacy could be increased by
      associating some other blood-saving method.

PMID- 24120596
TI  - Phosphatidylserine exposure on stored red blood cells as a parameter for donor
      dependent variation in product quality.
AB  - BACKGROUND: Exposure of phosphatidylserine on the outside of red blood cells
      contributes to recognition and removal of old and damaged cells. The fraction of
      phosphatidylserine-exposing red blood cells varies between donors, and increases
      in red blood cell concentrates during storage. The susceptibility of red blood
      cells to stress-induced phosphatidylserine exposure increases with storage.
      Phosphatidylserine exposure may, therefore, constitute a link between donor
      variation and the quality of red blood cell concentrates. MATERIALS AND METHODS:
      In order to examine the relationship between storage parameters and donor
      characteristics, the percentage of phosphatidylserine-exposing red blood cells
      was measured in red blood cell concentrates during storage and in fresh red blood
      cells from blood bank donors. The percentage of phosphatidylserine-exposing red
      blood cells was compared with red blood cell susceptibility to osmotic stress
      induced phosphatidylserine exposure in vitro, with the regular red blood cell
      concentrate quality parameters, and with the donor characteristics age, body mass
      index, haemoglobin level, gender and blood group. RESULTS: Phosphatidylserine
      exposure varies between donors, both on red blood cells freshly isolated from the
      blood, and on red blood cells in red blood cell concentrates. Phosphatidylserine
      exposure increases with storage time, and is correlated with stress-induced
      phosphatidylserine exposure. Increased phosphatidylserine exposure during storage
      was found to be associated with haemolysis and vesicle concentration in red blood
      cell concentrates. The percentage of phosphatidylserine-exposing red blood cells
      showed a positive correlation with the plasma haemoglobin concentration of the
      donor. DISCUSSION: The fraction of phosphatidylserine-exposing red blood cells is
      a parameter of red blood cell integrity in red blood cell concentrates and may be
      an indicator of red blood cell survival after transfusion. Measurement of
      phosphatidylserine exposure may be useful in the selection of donors and red
      blood cell concentrates for specific groups of patients.

PMID- 24120597
TI  - Cord blood serum-based eye drops: the impact of donor haematological and
      obstetric factors on the variability of epidermal growth factor levels.
AB  - BACKGROUND: Cord blood serum (CBS)-based eye drops are successfully used in
      corneal epithelial wound healing and are prepared to supply a known amount of
      epidermal growth factor (EGF). Product standardisation includes expensive EGF
      dosage in all cord blood (CB) units. The influence of donor obstetric and
      haematological characteristics on EGF content was evaluated, to exclude
      unsuitable CBS and pre-select those CB units able to provide the correct EGF
      supply for healing corneal wounds. MATERIALS AND METHODS: Data were
      retrospectively collected from 135 donors included in the Emilia Romagna Cord
      Blood Bank records. Obstetric characteristics, parity and gestational age of the
      mother, sex, birth weight and Apgar score of the neonate, placental weight,
      duration of labour and mode of delivery were considered. Haematological
      characteristics, CD34+ cell number, and total nucleated cell, white blood cell
      and platelet counts were recorded. EGF content in CB units was estimated by
      enzyme-linked immunosorbent assay. Statistical evaluation was performed by Mann
      Whitney unpaired and Student's t tests. Correlations between variables were
      evaluated by using Pearson's (r) or Spearman's (rho) correlation coefficients.
      RESULTS: EGF content was significantly higher in CBS from donors aged <30 years
      and after vaginal deliveries as compared with scheduled Caesarean sections
      (1,386+/-580 vs 1,106+/-391 pg/mL; P=0.002). EGF content was significantly
      correlated with duration of labour (r=0.45; P=0.0001), number of CD34+ cells/mL
      (r=0.3; P=0.002) particularly in vaginal deliveries (r=0.36; P=0.003), mother's
      age (-0.25; P=0.005), neonate's birth weight (r=0.27; P=0.005), and total
      nucleated cell (r=0.25; P=0.006), white cell (r=0.29; P=0.001) and platelet
      (r=0.24; P=0.009) counts. No significant correlations were found between EGF
      content and parity, gestational age, placental weight, neonate's sex or Apgar
      scores. DISCUSSION: EGF levels are higher in CB units from younger mothers (<30
      years), with longer labour duration (>6 hours), and higher CD34+ cell content
      (>0.05*10(6)/mL). In order to optimise the preparation and costs of CBS-based eye
      drops, pre-selection of CB units is recommended.

PMID- 24120598
TI  - Beyond immunohaematology: the role of the ABO blood group in human diseases.

PMID- 24120599
TI  - It is worthwhile filling in the remaining blank spots for blood group antigen
      frequencies.

PMID- 24120600
TI  - Rh phenotype, allele and haplotype frequencies among 51,857 blood donors in North
      India.
AB  - BACKGROUND: This study was performed to provide information on the frequencies of
      Rh antigens, alleles, phenotypes, and haplotypes from our region in India and to
      compare them with those from other races. MATERIALS AND METHODS: This
      observational study was conducted on blood donors from March 2009 to August 2011
      using a fully automated system for Rh typing of blood cells. The data were
      collected and calculations done to determine the antigen, phenotypes, allele and
      haplotype frequencies. The chi square test was used for comparisons between the
      results of our study and those of other studies. RESULTS: A total of 51,857
      donors were included in this study. The most common Rh antigen found was "e".
      DCCee was the most prevalent phenotype in our study with the phenotype
      distribution being significantly different between our study and other studies
      from different regions of the world. DISCUSSION: We have determined the
      prevalence of Rh antigens and Rh phenotypes in the North Indian blood donor
      population and derived the allele and haplotype frequencies in the same
      population. The Rh blood group distribution in this population was different from
      that in other populations.

PMID- 24120601
TI  - Low vacuum re-infusion drains after total knee arthroplasty: is there a real
      benefit?

PMID- 24120602
TI  - Alterations in HbA1c resulting from the donation of autologous blood for elective
      surgery in patients with diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to confirm the change in haemoglobin A1c
      consequent to pre-operative donation of autologous blood for elective surgery in
      patients with diabetes mellitus. MATERIAL AND METHODS: For enrolment in this
      prospective study, patients had to be scheduled for multiple autologous blood
      donations at different times and have a haemoglobin A1c level more than 5.8% at
      the first donation. The values of four factors, haemoglobin, haemoglobin A1c,
      glycated albumin, and glycated albumin/haemoglobin A1c ratio were determined.
      Changes in the values of these four factors between before and after the blood
      donations were calculated. RESULTS: In all 24 patients studied, haemoglobin and
      haemoglobin A1c decreased as a result of the autologous blood donations. The
      group with a reduced glycated albumin/haemoglobin A1c ratio had short intervals
      between blood donations. Correlations were observed between donation interval and
      change in haemoglobin A1c (r=-0.63, P=0.003), and between donation interval and
      change in the glycated albumin/haemoglobin A1c ratio (r=0.489, P=0.045).
      DISCUSSION: Haemoglobin A1c levels are likely to be underestimated after
      autologous blood donation by patients with diabetes mellitus, so glycated albumin
      may be a better indicator of these patients' glycaemic control.

PMID- 24120603
TI  - Extramedullary haematopoiesis correlates with genotype and absence of cardiac
      iron overload in polytransfused adults with thalassaemia.
AB  - BACKGROUND: The mechanisms responsible for the sporadic occurrence of
      extramedullary haematopoiesis in polytransfused thalassaemic patients have not
      yet been clarified. In this study we tried to elucidate the influence of genotype
      and other factors on the presence of extramedullary haematopoiesis. MATERIALS AND
      METHODS: We performed a retrospective database review of our polytransfused
      thalassaemic patients between January 2006 and December 2011. Demographic,
      transfusional, genetic, radiological and biochemical data were collected and
      statistically analysed. RESULTS: Extramedullary haematopoiesis was found in 18
      out of 67 patients (27%). All of them were splenectomised, had a higher nucleated
      red blood cell count and higher levels of the soluble form of transferrin
      receptor with respect to patients without extramedullary haematopoiesis;
      furthermore, patients with EMH had a lower transfusional iron intake and a higher
      pre-transfusion haemoglobin level as compared with those without extramedullary
      haematopoiesis. Ten out of the 18 patients with extramedullary haematopoiesis
      were compound heterozygotes for IVS 1-6/codon 39. A high frequency of thrombotic
      events was also recorded among all patients followed at our centre with this
      genetic profile. DISCUSSION: Among our cohort of thalassaemic polytransfused
      patients, extramedullary haematopoiesis was not such a rare event. Furthermore,
      we identified a group of patients, most of whom were compound heterozygotes for
      IVS 1-6/codon 39, with increased soluble transferrin receptor levels and
      excessive expansion of erythroid marrow probably responsible for the tendency to
      develop extramedullary haematopoiesis.

PMID- 24120604
TI  - Knowledge about umbilical cord blood banking among Greek citizens.
AB  - BACKGROUND: Umbilical cord blood supplies in Greece are not sufficient to meet
      the high transfusion needs. This study was designed to determine Greeks' opinion
      about umbilical cord blood, identify the reasons for the lack of motivation to
      donate umbilical cord blood and allow experts to establish better recruitment
      campaigns to enrich the donor pool. MATERIALS AND METHODS: The attitudes and
      knowledge about umbilical cord blood of randomly selected Greek citizens
      (n=1,019) were assessed by means of a standardised anonymous questionnaire. The
      results were analysed using the chi2 test and Spearman's correlation coefficient.
      RESULTS: Forty-eight percent of respondents knew about umbilical cord blood and
      had full knowledge about what storage/donation offers. Media (35%) and doctors
      (25%) were the main source of information. The information from the state was
      considered either inadequate or non-existent by 85% of the responders. Ninety
      five percent of the people questioned would like further information regarding
      umbilical cord blood transplantation and umbilical cord blood storage/donation.
      Six percent of the respondents who had children and were in favour of umbilical
      cord blood transplantation, had stored/donated UCB. With regards to future
      decisions, 84% of the sample would store/donate umbilical cord blood, of whom 57%
      would keep the umbilical cord blood in a private bank. DISCUSSION: It was
      concluded that Greek citizens receive information about umbilical cord blood from
      both the state and advertising campaigns by the Ministry of Health and Social
      Solidarity. A kind of cooperation between all hospitals and public umbilical cord
      blood banks would be advisable in order to facilitate access to umbilical cord
      blood donations.

PMID- 24120605
TI  - Current applications of therapeutic phlebotomy.

PMID- 24120606
TI  - Applying molecular immunohaematology to regularly transfused thalassaemic
      patients in Thailand.
AB  - BACKGROUND: Red blood cell transfusion is the principal therapy in patients with
      severe thalassaemias and haemoglobinopathies, which are prevalent in Thailand.
      Serological red blood cell typing is confounded by chronic transfusion, because
      of circulating donor red blood cells. We evaluated the concordance of serological
      phenotypes between a routine and a reference laboratory and with red cell
      genotyping. MATERIALS AND METHODS: Ten consecutive Thai patients with beta
      thalassemia major who received regular transfusions were enrolled in Thailand.
      Phenotypes were tested serologically at Songklanagarind Hospital and at the
      National Institutes of Health. Red blood cell genotyping was performed with
      commercially available kits and a platform. RESULTS: In only three patients was
      the red cell genotyping concordant with the serological phenotypes for five
      antithetical antigen pairs in four blood group systems at the two institutions.
      At the National Institutes of Health, 32 of the 100 serological tests yielded
      invalid or discrepant results. The positive predictive value of serology did not
      reach 1 for any blood group system at either of the two institutions in this set
      of ten patients. DISCUSSION: Within this small study, numerous discrepancies were
      observed between serological phenotypes at the two institutes; red cell
      genotyping enabled determination of the blood group when serology failed due to
      transfused red blood cells. We question the utility of serological tests in
      regularly transfused paediatric patients and propose relying solely on red cell
      genotyping, which requires training for laboratory personnel and physicians. Red
      cell genotyping outperformed red cell serology by an order of magnitude in
      regularly transfused patients.

PMID- 24120607
TI  - Immune thrombocytopenia successfully treated with eltrombopag following multiple
      therapies including romiplostim.

PMID- 24120608
TI  - The 2013 update of the "Seville Document": a Spanish multidisciplinary alliance
      for patient blood management.

PMID- 24120609
TI  - Surveillance of Chagas disease among at-risk blood donors in Italy: preliminary
      results from Umberto I Polyclinic in Rome.
AB  - BACKGROUND: Chagas disease is a parasitic disease due to Trypanosoma cruzi,
      endemic in Central and Southern America, where the protozoon infects about 8-10
      million people. In rural areas the infection is acquired mostly through
      reduviidae insect vectors, whereas in urban ones it is acquired mainly through
      the transfusion of blood products, vertical transmission and organ
      transplantation. The important migratory flows of the last decades have focused
      attention on possible T. cruzi transmission by transfusion also in non-endemic
      countries, and platelets have been recognised as the main origin of infection for
      recipients from serologically-positive Latino-American donors. MATERIALS AND
      METHODS: In order to avoid the occurrence of transfusion-related cases, in 2010
      systematic screening for anti-T. cruzi antibodies was started at the Umberto I
      Polyclinic in Rome, controlling blood donors born and/or coming from Latin
      American countries in which the disease is endemic. The aim of this paper is to
      report the preliminary results achieved since the introduction of this screening.
      RESULTS: Anti-T. cruzi antibodies have been detected to date in 3.9% out of the
      128 people examined. A seropositive subject also proved positive by polymerase
      chain reaction analysis and showed very light parasitaemia. DISCUSSION: The
      preliminary results are quite alarming. Indeed, serological findings exceed those
      reported in other non-endemic countries, and Italian travellers proved to be an
      insidious possible source of direct transmission. The need for systematic
      screening of at-risk blood donors also in non-endemic countries is emphasised.

PMID- 24120610
TI  - West Nile virus in the transfusion setting with a special focus on Italian
      preventive measures adopted in 2008-2012 and their impact on blood safety.

PMID- 24120611
TI  - SIMTI recommendations on blood components for non-transfusional use.

PMID- 24120612
TI  - Neural correlates of shape-color binding in visual working memory.
AB  - The present study addressed an outstanding issue regarding feature binding in
      working memory (WM): whether this function engages specific resources relative to
      those required to process individual features. We investigated the brain regions
      supporting the encoding and maintenance of features and bindings in a change
      detection task, in which 22 healthy young volunteers remembered visual arrays of
      abstract shapes, colors or shape-color bindings while undergoing fMRI. After an
      unfilled delay they saw a second array and judged whether the features or
      combination of features presented across the two arrays were the same or
      different. Temporary retention of feature bindings was found to involve
      additional cortical regions compared with retaining single features, regardless
      of whether the number of objects or the number of features differed between
      feature-only and binding conditions. This binding-specific activation is
      consistent with the involvement of different neural generators that collectively
      support visual temporary memory for features and for feature bindings. Regions
      within the parietal, temporal and occipital cortex, but not within the prefrontal
      cortex or the medial temporal lobe, appear to support the integrated object
      binding function investigated in this study. Our findings suggest that both
      individual features and their binding within integrated objects are used to
      represent complex objects in WM. 

PMID- 24120613
TI  - Comment on "Dysregulated expression of T cell immunoglobulin and mucin domain 3
      is associated with the disease severity and the outcome of patients with
      spontaneous intracerebral hemorrhage".

PMID- 24120614
TI  - Neuroimaging changes in the brain in contact versus noncontact sport athletes
      using diffusion tensor imaging.
AB  - OBJECTIVE: Traumatic brain injury in contact sports has significant impact on
      short-term neurologic and neurosurgical function as well as longer-term cognitive
      disability. In this study, we aim to demonstrate that contact sport participants
      exhibit differences in diffusion tensor imaging (DTI) caused by repeated physical
      impacts on the brain. We also aim to determine that impact incurred by the
      contact sports athletes during the season may result in the differences between
      the pre- and postseason DTI scans. METHODS: DTI data were collected from 10
      contact-sport (mean age 20.4 +/- 1.36 years) and 13 age-matched noncontact-sport
      (mean age 19.5 +/- 1.03 years) male athletes on a 3-Tesla magnetic resonance
      imaging scanner. A single-shot, echo-planar imaging sequence with b-value of 1000
      s/mm(2) and 25 gradient directions was used. Eight of the athletes were again
      scanned after the end of the season. The b0 nondiffusion-weighted image was
      averaged five times. Voxel-wise, two-sample t tests were run for all group
      comparisons, and in each case, the positive false-discovery rate was computed to
      assess the whole-map, multiple-comparison corrected significance. RESULTS: There
      were significant differences in the fractional anisotropy values in the inferior
      fronto-occipital fasciculus, parts of the superior and posterior coronal radiate,
      and the splenium of the corpus callosum (CC) as well as smaller clusters in the
      genu and parts of the body of the CC. In addition, the external capsule also
      shows some difference between the contact and noncontact athlete brains. In
      addition, the preseason and postseason showed differences in these regions,
      however, the postseason P-values show significance in more areas of the CC.
      CONCLUSIONS: There are significant DTI changes in the CC, the external capsule,
      the inferior fronto-occipital fasciculus, as well as regions such as the
      superior/posterior corona radiata the preseason contact versus the noncontact
      control athletes were compared and also when the postseason contact athletes with
      the control athletes were compared.

PMID- 24120615
TI  - Management of incompletely coiled aneurysms: to treat or not to treat?

PMID- 24120616
TI  - Postconcussion syndrome: a complex and underdiagnosed clinical entity.

PMID- 24120617
TI  - Treatment of trigeminal neuralgia associated with multiple sclerosis.

PMID- 24120618
TI  - Effects of a nitrate-rich meal on arterial stiffness and blood pressure in
      healthy volunteers.
AB  - An increase in nitrate intake can augment circulating nitrite and nitric oxide.
      This may lead to lower blood pressure and improved vascular function. Green leafy
      vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the
      acute effects of a nitrate-rich meal containing spinach on arterial stiffness and
      blood pressure in healthy men and women. Twenty-six participants aged 38-69years
      were recruited to a randomized controlled cross-over trial. The acute effects of
      two energy-matched (2000kJ) meals, administered in random order, were compared.
      The meals were either high nitrate (220mg of nitrate derived from spinach
      [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal
      and at specific time points up to 210min post meal. Spinach resulted in an
      eightfold increase in salivary nitrite and a sevenfold increase in salivary
      nitrate concentrations from pre-meal (P<0.001) to 120min post meal. Spinach
      compared with control resulted in higher large artery elasticity index (P<0.001),
      and lower pulse pressure (P<0.001) and systolic blood pressure (P<0.001). Post
      meal carotid-femoral pulse wave velocity (P=0.07), augmentation index (P=0.63),
      small artery elasticity index (P=0.98) and diastolic blood pressure (P=0.13) were
      not significantly altered by spinach relative to control. Therefore, consumption
      of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and
      increase large artery compliance acutely in healthy men and women. If sustained,
      these effects could contribute to better cardiovascular health. 

PMID- 24120619
TI  - Genome-wide identification of allele-specific effects on gene expression for
      single and multiple individuals.
AB  - The analysis of allele-specific gene expression (ASE) is essential for the
      mapping of genetic variants that affect gene regulation, and for the
      identification of alleles that modify disease risk. Although RNA sequencing
      offers the opportunity to measure expression at allele levels, the availability
      of powerful statistical methods for mapping ASE in single or multiple individuals
      is limited. We developed a maximum likelihood model to characterize ASE in the
      human genome. Approximately 17% of genes displayed an allele-specific effect on
      gene expression in a single individual. Simulations using our model gave a better
      performance and improved robustness when compared with the binomial test, with
      different coverage levels, allelic expression fractions and random noise. In
      addition, our method can identify ASE in multiple individuals, with enhanced
      performance. This is helpful in understanding the mechanism of genetic regulation
      leading to expression changes, alternative splicing variants and even disease
      susceptibility. 

PMID- 24120620
TI  - Selected isomiR expression profiles via arm switching?
AB  - A mature miRNA may be generated from 5p or 3p arm of a hairpin precursor. The
      selection may be flexible via "arm switching". However, accumulating evidences
      suggest that both arms of many pre-miRNAs can yield mature functional miRNAs.
      Herein, we attempted to compare the isomiR expression profiles between the two
      arms through analyzing in-house and published small RNA deep sequencing datasets.
      Although many miR-#-5p and miR-#-3p have been reported as functional miRNAs,
      fewer miRNA pairs (11 and 6 pairs are collected in tumor and normal cells,
      respectively) are simultaneously identified as abundant miRNA species. According
      to isomiR types and dominant isomiR species, miR-#-5p and miR-#-3p show various
      isomiR expression profiles as well as diverse enrichment levels. IsomiR profiles
      of non-dominant arm are not well-conserved in 5' ends as well as isomiR profiles
      of dominant arm. If both the miR-#-5p and miR-#-3p are abundantly expressed,
      their isomiR expression profiles are always stable across different samples.
      Similar to diverse enrichment levels of miR-#-5p and miR-#-3p, the isomiR
      expression patterns may also be influenced by the phenomenon of "arm switching".
      The diverged isomiR expression profiles further enrich the complexity of multiple
      isomiRs, and complicate the coding-non-coding RNA regulatory network. 

PMID- 24120621
TI  - Understanding the function of bacterial and eukaryotic thiolases II by
      integrating evolutionary and functional approaches.
AB  - Acetoacetyl-CoA thiolase (EC 2.3.1.9), commonly named thiolase II, condenses two
      molecules of acetyl-CoA to give acetoacetyl-CoA and CoA. This enzyme acts in
      anabolic processes as the first step in the biosynthesis of isoprenoids and
      polyhydroxybutyrate in eukaryotes and bacteria, respectively. We have recently
      reported the evolutionary and functional equivalence of these enzymes, suggesting
      that thiolase II could be the rate limiting enzyme in these pathways and
      presented evidence indicating that this enzyme modulates the availability of
      reducing equivalents during abiotic stress adaptation in bacteria and plants.
      However, these results are not sufficient to clarify why thiolase II was
      evolutionary selected as a critical enzyme in the production of antioxidant
      compounds. Regarding this intriguing topic, we propose that thiolase II could
      sense changes in the acetyl-CoA/CoA ratio induced by the inhibition of the
      tricarboxylic acid cycle under abiotic stress. Thus, the high level of
      evolutionary and functional constraint of thiolase II may be due to the
      connection of this enzyme with an ancient and conserved metabolic route. 

PMID- 24120622
TI  - The calcium-sensing receptor R990G polymorphism is associated with increased risk
      of hypertriglyceridemia in obese Chinese.
AB  - BACKGROUND: We have demonstrated that the calcium-sensing receptor (CaSR) is
      involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid
      metabolism in obesity is still unclear. The present study aimed to determine the
      effects of CaSR polymorphisms on HTG risk in obese Chinese. METHODS: A total of
      972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by
      body mass index (BMI) into normal weight, overweight or obesity subgroups. After
      12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum
      lipids and glucose, as well as height, body weight and waist circumference were
      measured. The anthropometric and metabolic characteristics of the NTG subjects
      were re-evaluated 3 years later. RESULTS: There were no genotypic or allelic
      distribution differences for the A986S or Q1011E polymorphisms between the NTG
      and HTG groups. However, the G/G genotypic and G allelic distributions of the
      CaSR R990G polymorphism in the HTG group were higher than the NTG group
      (p<0.001). After stratification, in obese subjects, the homozygous (G/G)
      distribution of the CaSR R990G polymorphism in the HTG group was significantly
      higher than in the NTG group (p=0.001), and showed an increased risk of HTG at
      baseline [OR=2.55, 95% CI=1.65-3.92, p<0.006]. Interaction of the CaSR R990G
      polymorphism with BMI was associated with increased risk of HTG (beta=0.927,
      p<0.001). Re-evaluation of the NTG subjects revealed significantly increased
      serum triglyceride levels in obese homozygous versus wildtype carriers (p<0.05).
      CONCLUSIONS: These results suggest that the CaSR R990G polymorphism is associated
      with increased risk of HTG, especially in obese Chinese, and may be a potential
      genetic predictor of diseases related to HTG.

PMID- 24120623
TI  - Molecular evolution and nucleotide diversity of nuclear plastid phosphoglycerate
      kinase (PGK) gene in Triticeae (Poaceae).
AB  - Levels of nucleotide divergence provide key evidence in the evolution of
      polyploids. The nucleotide diversity of 226 sequences of pgk1 gene in Triticeae
      species was characterized. Phylogenetic analyses based on the pgk1 gene were
      carried out to determine the diploid origin of polyploids within the tribe in
      relation to their A(u), B, D, St, Ns, P, and H haplomes. Sequences from the Ns
      genome represented the highest nucleotide diversity values for both polyploid and
      diploid species with pi=0.03343 and theta=0.03536 for polyploid Ns genome
      sequences and pi=0.03886 and theta=0.03886 for diploid Psathyrostachys sequences,
      while Triticum urartu represented the lowest diversity among diploid species at
      pi=0.0011 and theta=0.0011. Nucleotide variation of diploid Aegilops speltoides
      (pi=0.2441, presumed the B genome donor of Triticum species) is five times higher
      than that (pi=0.00483) of B genome in polyploid species. Significant negative
      Tajima's D values for the St, A(u), and D genomes along with high rates of
      polymorphisms and low sequence diversity were observed. Origins of the A(u), B,
      and D genomes were linked to T. urartu, A. speltoides, and A. tauschii,
      respectively. Putative St genome donor was Pseudoroegneria, while Ns and P donors
      were Psathyrostachys and Agropyron. H genome diploid donor is Hordeum. 

PMID- 24120624
TI  - Three single nucleotide variants of the HDAC gene are associated with type 2
      diabetes mellitus in a Chinese population: a community-based case-control study.
AB  - OBJECTIVES: There are no data regarding the possible role of the single
      nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2
      diabetes mellitus (DM). We designed this study to examine whether polymorphisms
      of HDACs can be implicated in that disease. METHODS: A community-based, case
      control study was conducted, with a total of 568 subjects (284 patients and 284
      controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3
      (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.
      RESULTS: We found a significant association with risk of type 2 DM for three SNPs
      of HDAC3, including rs11741808 [odds ratio (OR)=0.53, 95% confidence interval
      (CI): 0.35-0.81], rs2547547 [OR=1.72, 95% CI: 1.13-2.64], and rs2530223 [OR=1.39;
      95% CI: 1.01-1.91]. Subgroup analysis showed that BMI>=23kg/m(2), high
      triglyceride and high blood pressure, together with the rs11741808AG genotype,
      were associated with a significantly decreased risk for type 2 DM, with ORs of
      0.50 (95% CI: 0.27-0.91), 0.38 (95% CI: 0.20-0.71) and 0.43 (95% CI: 0.24-0.76)
      compared with the AA genotype, respectively. In a population with normal total
      cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM
      risk, with an OR of 0.42 (95% CI: 0.25-0.70) when compared with the persons of
      the AA genotype. For rs2547547, in a population with normal total cholesterol and
      triglyceride, the AG genotype was associated with a significantly increased risk
      of type 2 DM, with ORs of 1.92 (95% CI: 1.17-3.15) and 2.24 (95% CI: 1.28-3.94)
      when compared with the population carrying the AA genotype. CONCLUSIONS: The
      results suggest that variants of HDAC3 contribute to an increased prevalence of
      type 2 DM in the Chinese Han population.

PMID- 24120625
TI  - The complete mitochondrial genome of a turbinid vetigastropod from MiSeq Illumina
      sequencing of genomic DNA and steps towards a resolved gastropod phylogeny.
AB  - A need to increase sampling of mitochondrial genomes for Vetigastropoda has been
      identified as an important step towards resolving relationships within the
      Gastropoda. We used shotgun sequencing of genomic DNA, using an Illumina MiSeq,
      to obtain the first mitochondrial genome for the vetigastropod family Turbinidae,
      doubling the number of genomes for the species-rich superfamily Trochoidea. This
      method avoids the necessity of finding suitable primers for long PCRs or primer
      walking amplicons, resulting in a timely and cost-effective method for obtaining
      whole mitochondrial genomes from ethanol-preserved tissue samples. Bayesian
      analysis of amino acid variation for all available gastropod genomes including
      the new turbinid mtgenome produced a well resolved tree with high nodal support
      for most nodes. Major clades within Gastropoda were recovered with strong
      support, with the exception of Littorinimorpha, which was polyphyletic. We
      confirm here that mitogenomics is a useful tool for molluscan phylogenetics,
      especially when using powerful new models of amino acid evolution, but recognise
      that increased taxon sampling is still required to resolve existing differences
      between nuclear and mitochondrial gene trees.

PMID- 24120626
TI  - Midgut transcriptome response to a Cry toxin in the diamondback moth, Plutella
      xylostella (Lepidoptera: Plutellidae).
AB  - To investigate the response of Plutella xylostella transcriptome in defending
      against a Bt toxin, high-throughput RNA-sequencing was carried out to examine
      Cry1Ac-susceptible and -resistant strains. The comparative analysis indentified
      over 2900 differentially expressed unigenes (DEUs) between these two strains.
      Gene Ontology analysis placed these unigenes primarily into cell, cell part,
      organelle, binding, catalytic, cellular process, metabolic process, and response
      to stimulus categories. Based on pathway analyses, DEUs were enriched in
      oxidoreductase activity and membrane lipid metabolic processes, and they were
      also significantly enriched in pathways related to the metabolic and biosynthesis
      of secondary metabolites. Most of the unigenes involved in the metabolic pathway
      were up-regulated in resistant strains. Within the ABC transporter pathway,
      majority of the down-regulated unigenes belong to ABCC2 and ABCC10, respectively,
      while up-regulated unigenes were mainly categorized as ABCG2. Furthermore, two
      aminopeptidases, and four cadherins encoding genes were significantly elevated as
      well. This study provides a transcriptome foundation for the identification and
      functional characterization of genes involved in the Bt resistance in an
      agriculturally important insect pest, P. xylostella. 

PMID- 24120627
TI  - Implementing the central venous catheter infection prevention bundle in the
      emergency department: experiences among early adopters.
AB  - STUDY OBJECTIVE: Central line-associated bloodstream infections (CLABSI) cause
      preventable morbidity and mortality. Hospitals have reduced CLABSI by using a
      bundle of evidence-based infection prevention practices. Systems factors in the
      emergency department (ED) present unique barriers to bundle adoption, and no
      guidelines exist for bundle implementation. We aim to identify barriers and
      facilitators to central line bundle adoption in EDs. METHODS: We used a
      qualitative, grounded theory approach, enrolling 6 EDs that were early adopters
      of the central line bundle. We interviewed 49 administrators and staff (nurses
      and physicians) through 26 semistructured interviews and 3 focus groups of 6 to 8
      individuals. Investigators read each transcript and then iteratively built and
      refined a set of themes that emerged from the data. RESULTS: Barriers to central
      line bundle adoption included high acuity, time constraints, staffing, space, ED
      culture, high ED volume and acuity, role ambiguity, and a lack of methods to
      track compliance and infection surveillance. Facilitators included champions,
      staff engagement, workflow redesign that includes a checklist and central line
      kit or cart, clear staff responsibilities, observer empowerment, and compliance
      and infection surveillance data. CONCLUSION: The strategies for implementing and
      sustaining a central line infection prevention bundle in the ED are distinct from
      those of other clinical settings. Our findings describe the central line bundle
      workflow in the ED, staff motivations, and the critical systems factors that
      impede and foster its use. Knowledge of these systems factors should improve
      bundle adoption in the ED and thereby reduce hospital incidence of CLABSIs.

PMID- 24120628
TI  - Sweet solutions and needle-related pain in infants.

PMID- 24120629
TI  - Outcomes and radiation exposure of emergency department patients with chest pain
      and shortness of breath and ultralow pretest probability: a multicenter study.
AB  - STUDY OBJECTIVE: Excessive radiation exposure remains a concern for patients with
      symptoms suggesting acute coronary syndrome and pulmonary embolism but must be
      judged in the perspective of pretest probability and outcomes. We quantify and
      qualify the pretest probability, outcomes, and radiation exposure of adults with
      both chest pain and dyspnea. METHODS: This was a prospective, 4-center, outcomes
      study. Patients were adults with dyspnea and chest pain, nondiagnostic ECGs, and
      no obvious diagnosis. Pretest probability for both acute coronary syndrome and
      pulmonary embolism was assessed with a validated method; ultralow risk was
      defined as pretest probability less than 2.5% for both acute coronary syndrome
      and pulmonary embolism. Patients were followed for diagnosis and total medical
      radiation exposure for 90 days. RESULTS: Eight hundred forty patients had
      complete data; 23 (3%) had acute coronary syndrome and 15 (2%) had pulmonary
      embolism. The cohort received an average of 4.9 mSv radiation to the chest, 48%
      from computed tomography pulmonary angiography. The pretest probability estimates
      for acute coronary syndrome and pulmonary embolism were less than 2.5% in 227
      patients (27%), of whom 0 of 277 (0%; 95% confidence interval 0% to 1.7%) had
      acute coronary syndrome or pulmonary embolism and 7 of 227 (3%) had any
      significant cardiopulmonary diagnosis. The estimated chest radiation exposure per
      patient in this ultralow-risk group was 3.5 mSv, including 26 (3%) with greater
      than 5 mSv radiation to the chest and no significant cardiopulmonary diagnosis.
      CONCLUSION: One quarter of patients with chest pain and dyspnea had ultralow risk
      and no acute coronary syndrome or pulmonary embolism but were exposed to an
      average of 3.5 mSv radiation to the chest. These data can be used in a clinical
      guideline to reduce radiation exposure.

PMID- 24120630
TI  - Risk factors for apnea in pediatric patients transported by paramedics for out-of
      hospital seizure.
AB  - STUDY OBJECTIVE: Apnea is a known complication of pediatric seizures, but patient
      factors that predispose children are unclear. We seek to quantify the risk of
      apnea attributable to midazolam and identify additional risk factors for apnea in
      children transported by paramedics for out-of-hospital seizure. METHODS: This is
      a 2-year retrospective study of pediatric patients transported by paramedics to 2
      tertiary care centers. Patients were younger than 15 years and transported by
      paramedics to the pediatric emergency department (ED) for seizure. Patients with
      trauma and those with another pediatric ED diagnosis were excluded. Investigators
      abstracted charts for patient characteristics and predefined risk factors:
      developmental delay, treatment with antiepileptic medications, and seizure on
      pediatric ED arrival. Primary outcome was apnea defined as bag-mask ventilation
      or intubation for apnea by paramedics or by pediatric ED staff within 30 minutes
      of arrival. RESULTS: There were 1,584 patients who met inclusion criteria, with a
      median age of 2.3 years (Interquartile range 1.4 to 5.2 years). Paramedics
      treated 214 patients (13%) with midazolam. Seventy-one patients had apnea (4.5%):
      44 patients were treated with midazolam and 27 patients were not treated with
      midazolam. After simultaneous evaluation of midazolam administration, age, fever,
      developmental delay, antiepileptic medication use, and seizure on pediatric ED
      arrival, 2 independent risk factors for apnea were identified: persistent seizure
      on arrival (odds ratio [OR]=15; 95% confidence interval [CI] 8 to 27) and
      administration of field midazolam (OR=4; 95% CI 2 to 7). CONCLUSION: We
      identified 2 risk factors for apnea in children transported for seizure: seizure
      on arrival to the pediatric ED and out-of-hospital administration of midazolam.

PMID- 24120631
TI  - "No diversion": a qualitative study of emergency medicine leaders in Boston, MA,
      and the effects of a statewide diversion ban policy.
AB  - STUDY OBJECTIVE: We examine the attitudes of emergency department (ED) key
      informants about the perceived effects of a statewide ban on ambulance diversion
      on patients, providers, and working relationships in a large urban emergency
      medical system. METHODS: We performed a qualitative study to examine the effects
      of a diversion ban on Boston area hospitals. Key informants at each site
      completed semistructured interviews that explored relevant domains pre- and
      postban. Interviews were deidentified, transcribed, coded, and analyzed with
      grounded theory for emerging themes. We identified important themes focused on
      patient safety, quality of care, and relationships before and after
      implementation of the diversion ban. RESULTS: Nine of 9 eligible sites
      participated. Eighteen interviews were completed: 7 MD ED directors, 2 MD
      designees, and 9 registered nurse leaders. Although most participants had
      negative opinions about diversion, some had considered diversion a useful
      procedure. Key themes associated with diversion were adverse effects on patient
      care quality, patient satisfaction, and a source of conflict among ED staff and
      with emergency medical services (EMS). All key informants described some positive
      effect of the ban, including those who reported that the ban had no direct effect
      on their individual hospital. Although the period preceding the ban was reported
      to be a source of apprehension about its effects, most key informants believed
      the ban had improved quality of care and relationships between hospital staff and
      EMS. CONCLUSION: Key informants considered the diversion ban to have had a
      favorable effect on emergency medical care in Boston. These results may inform
      the discussion in other states considering a diversion ban.

PMID- 24120632
TI  - LUNX mRNA-positive cells at different time points predict prognosis in patients
      with surgically resected nonsmall cell lung cancer.
AB  - LUNX is a lung-specific gene whose messenger ribonucleic acid (mRNA) expression
      is strictly limited to normal lung tissue and nonsmall cell lung cancer (NSCLC)
      tissue. The aim of this study was to investigate whether the detection of LUNX
      mRNA-positive circulating tumor cells (CTC)s in peripheral blood at different
      time points is useful for predicting disease recurrence, disease-free survival
      (DFS), and overall survival (OS) in NSCLC patients undergoing surgery. Serial
      blood samples from 68 patients with stage I-IIIA NSCLC were examined by real-time
      quantitative polymerase chain reaction assay targeting LUNX mRNA before (T0) and
      after surgery (T1) and after the completion of adjuvant chemotherapy (T2).
      Results showed that LUNX mRNA-positive CTCs were detected in 40 of 68 NSCLC
      patients (58.8%) before surgery; the detection rates of LUNX mRNA-positive CTCs
      at T1 and T2 time points were 32.4% (22/68) and 33.3% (20/60), respectively. The
      detection of LUNX mRNA-positive CTC at 3 time points was associated with lymph
      node status and pathologic stage. During the follow-up period, patients with LUXN
      mRNA-positive CTC at 3 time points had a higher relapse rate and a shorter DFS
      and OS than those without. Multivariate analysis revealed that presence of LUNX
      mRNA-positive CTC at T1 and T2 time points was an independent unfavorable factor
      for DFS and OS. In conclusion, detection of LUNX mRNA-positive CTC after surgery
      and the completion of adjuvant chemotherapy in patients with stage I-IIIA NSCLC
      are highly predictive for DFS and OS. This technique could aid in the prediction
      of prognosis and design of tailored treatment. 

PMID- 24120633
TI  - Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus
      of the solitary tract.
AB  - Brainstem structures such as the nucleus of the solitary tract (NTS) and the
      dorsal motor nucleus of the vagus nerve (DMNX) are essential for the digestive
      function of the stomach. A large number of neurotransmitters including glutamate
      and gamma-aminobutyric acid (GABA) are involved in the central control of gastric
      functions. However, the neuropeptidergic systems implicated in this process
      remain undetermined. Nesfatin-1 was recently identified as a neuropeptide cleaved
      from the N-terminal part of NEFA/nucleobindin 2 precursor (NUCB2). Central
      administration of this neuropeptide inhibits food consumption and gastroduodenal
      motility in rodents. Interestingly, the NTS and the DMNX contain a dense
      population of NUCB2/nesfatin-1 cell bodies. These observations led us to
      investigate the possible involvement of NUCB2/nesfatin-1 neurons in the brainstem
      neuronal pathways that modulate gastric functions. We observed an activation of
      NTS NUCB2/nesfatinergic neurons after gastric distention in rats. In addition, we
      found that several NTS NUCB2/nesfatinergic neurons were GABAergic. Finally, when
      fluorogold was injected at the stomach level, many retrogradely labeled neurons
      were observed in the DMNX which were also positive for NUCB2/nesfatin-1. Taken
      together, these observations suggest for the first time that NUCB2/nesfatin-1
      neurons of the NTS are sensitive to gastric distension and then may contribute to
      the satiety signal. 

PMID- 24120635
TI  - African elephants can use human pointing cues to find hidden food.
AB  - How animals gain information from attending to the behavior of others has been
      widely studied, driven partly by the importance of referential pointing in human
      cognitive development [1-4], but species differences in reading human social cues
      remain unexplained. One explanation is that this capacity evolved during
      domestication [5, 6], but it may be that only those animals able to interpret
      human-like social cues were successfully domesticated. Elephants are a critical
      taxon for this question: despite their longstanding use by humans, they have
      never been domesticated [7]. Here we show that a group of 11 captive African
      elephants, seven of them significantly as individuals, could interpret human
      pointing to find hidden food. We suggest that success was not due to prior
      training or extensive learning opportunities. Elephants successfully interpreted
      pointing when the experimenter's proximity to the hiding place was varied and
      when the ostensive pointing gesture was visually subtle, suggesting that they
      understood the experimenter's communicative intent. The elephant's native ability
      in interpreting social cues may have contributed to its long history of effective
      use by man. 

PMID- 24120634
TI  - Exposure to caregiver maltreatment alters expression levels of epigenetic
      regulators in the medial prefrontal cortex.
AB  - Quality of maternal care experienced during infancy is a key factor that can
      confer vulnerability or resilience to psychiatric disorders later in life.
      Research continues to indicate that early-life experiences can affect
      developmental trajectories through epigenetic alterations capable of affecting
      gene regulation and neural plasticity. Previously, our lab has shown that
      experiences within an adverse caregiving environment (i.e. maltreatment) produce
      aberrant DNA methylation patterns at various gene loci in the medial prefrontal
      cortex (mPFC) of developing and adult rats. This study aimed to determine whether
      caregiver maltreatment likewise affects expression levels of several genes
      important in regulating DNA methylation patterns (Dnmt1, Dnmt3a, MeCP2, Gadd45b,
      and Hdac1). While we observed minimal changes in gene expression within the mPFC
      of developing rats, we observed expression changes for all genes in adult
      animals. Specifically, exposure to maltreatment produced a significant decrease
      in mRNA levels of all epigenetic regulators in adult males and a significant
      decrease in Gadd45b in adult females. Our results here provide further empirical
      support for the long-term and sex-specific epigenetic consequences of caregiver
      maltreatment on the mPFC. 

PMID- 24120636
TI  - Rapid innate defensive responses of mice to looming visual stimuli.
AB  - Much of brain science is concerned with understanding the neural circuits that
      underlie specific behaviors. While the mouse has become a favorite experimental
      subject, the behaviors of this species are still poorly explored. For example,
      the mouse retina, like that of other mammals, contains ~20 different circuits
      that compute distinct features of the visual scene [1, 2]. By comparison, only a
      handful of innate visual behaviors are known in this species--the pupil reflex
      [3], phototaxis [4], the optomotor response [5], and the cliff response [6]--two
      of which are simple reflexes that require little visual processing. We explored
      the behavior of mice under a visual display that simulates an approaching object,
      which causes defensive reactions in some other species [7, 8]. We show that mice
      respond to this stimulus either by initiating escape within a second or by
      freezing for an extended period. The probability of these defensive behaviors is
      strongly dependent on the parameters of the visual stimulus. Directed experiments
      identify candidate retinal circuits underlying the behavior and lead the way into
      detailed study of these neural pathways. This response is a new addition to the
      repertoire of innate defensive behaviors in the mouse that allows the detection
      and avoidance of aerial predators.

PMID- 24120637
TI  - An atypical tubulin kinase mediates stress-induced microtubule depolymerization
      in Arabidopsis.
AB  - BACKGROUND: As sessile organisms, plants adapt to adverse environmental
      conditions by quickly adjusting cell physiology and metabolism. Transient
      depolymerization of interphase microtubules is triggered by various acute
      stresses and biotic interactions with pathogenic organisms. Although rapid
      remodeling of plant microtubule arrays in response to external stresses is an
      intriguing phenomenon, the underlying molecular mechanisms and the advantages of
      this response to plant performance are poorly understood. RESULTS: A domain with
      weak homology to the slime mold actin-fragmin kinase in the Arabidopsis mitogen
      activated protein kinase phosphatase PROPYZAMIDE-HYPERSENSITIVE 1 (PHS1) is a
      Mn2+-dependent kinase. This atypical kinase domain phosphorylates Thr349 of alpha
      tubulin at the longitudinal interdimer interface, thereby generating a
      polymerization-incompetent isoform, and effectively depolymerizes microtubule
      arrays when ectopically expressed in plant or animal cells. The intrinsic tubulin
      kinase activity is normally suppressed by the phosphatase activity of PHS1 but is
      unmasked immediately after osmotic stress. In the phs1 null mutant, stress
      induced microtubule depolymerization does not occur. CONCLUSIONS: The rapid and
      reversible modification of tubulin subunits by PHS1-mediated phosphorylation
      enables dynamic remodeling of the plant microtubule cytoskeleton in response to
      external stimuli. Suppression of the potent tubulin kinase activity by the
      juxtaposed phosphatase domain tightly controls this stress-activated microtubule
      regulator.

PMID- 24120638
TI  - Chemical signals synchronize the life cycles of a plant-parasitic nematode and
      its vector beetle.
AB  - The pinewood nematode Bursaphelenchus xylophilus has caused severe damage to pine
      forests in large parts of the world [1-4]. Dispersal of this plant-parasitic
      nematode occurs when the nematode develops into the dispersal fourth larval stage
      (LIV) upon encountering its insect vector, the Monochamus pine sawyer beetle,
      inside an infected pine tree [5-9]. Here, we show that LIV formation in B.
      xylophilus is induced by C16 and C18 fatty acid ethyl esters (FAEEs), which are
      produced abundantly on the body surface of the vector beetle specifically during
      the late development pupal, emerging adult, and newly eclosed adult stages. The
      LIV can then enter the tracheal system of the adult beetle for dispersal to a new
      pine tree. Treatment of B. xylophilus with long-chain FAEEs, or the PI3 kinase
      inhibitor LY294002, promotes LIV formation, while Delta7-dafachronic acid blocks
      the effects of these chemicals, suggesting a conserved role for the insulin/IGF-1
      and DAF-12 pathways in LIV formation. Our work provides a mechanism by which LIV
      formation in B. xylophilus is specifically coordinated with the life cycle of its
      vector beetle. Knowledge of the chemical signals that control the LIV
      developmental decision could be used to interfere with the dispersal of this
      plant-parasitic nematode.

PMID- 24120639
TI  - An Arf-GEF regulates antagonism between endocytosis and the cytoskeleton for
      Drosophila blastoderm development.
AB  - BACKGROUND: Actin cytoskeletal networks push and pull the plasma membrane (PM) to
      control cell structure and behavior. Endocytosis also regulates the PM and can be
      promoted or inhibited by cytoskeletal networks. However, endocytic regulation of
      the general membrane cytoskeleton is undocumented. RESULTS: Here, we provide
      evidence for endocytic inhibition of actomyosin networks. Specifically, we find
      that Steppke, a cytohesin Arf-guanine nucleotide exchange factor (GEF), controls
      initial PM furrow ingression during the syncytial nuclear divisions and
      cellularization of the Drosophila embryo. Acting at the tips of ingressing
      furrows, Steppke promotes local endocytic events through its Arf-GEF activity and
      in cooperation with the AP-2 clathrin adaptor complex. These Steppke activities
      appear to reduce local Rho1 protein levels and ultimately restrain actomyosin
      networks. Without Steppke, Rho1 pathways linked to actin polymerization and
      myosin activation abnormally expand the membrane cytoskeleton into taut sheets
      emanating perpendicularly from the furrow tips. These expansions lead to
      premature cellularization and abnormal expulsions of nuclei from the forming
      blastoderm. Finally, consistent with earlier reports, we also find that
      actomyosin activity can act reciprocally to inhibit the endocytosis at furrow
      tips. CONCLUSIONS: We propose that Steppke-dependent endocytosis keeps the
      cytoskeleton in check as early PM furrows form. Specifically, a cytohesin Arf-GEF
      Arf G protein-AP-2 endocytic axis appears to antagonize Rho1 cytoskeletal
      pathways to restrain the membrane cytoskeleton. However, as furrows lengthen
      during cellularization, the cytoskeleton gains strength, blocks the endocytic
      inhibition, and finally closes off the base of each cell to form the blastoderm.

PMID- 24120640
TI  - Visualization of neural activity in insect brains using a conserved immediate
      early gene, Hr38.
AB  - Many insects exhibit stereotypic instinctive behavior [1-3], but the underlying
      neural mechanisms are not well understood due to difficulties in detecting brain
      activity in freely moving animals. Immediate early genes (IEGs), such as c-fos,
      whose expression is transiently and rapidly upregulated upon neural activity, are
      powerful tools for detecting behavior-related neural activity in vertebrates [4,
      5]. In insects, however, this powerful approach has not been realized because no
      conserved IEGs have been identified. Here, we identified Hr38 as a novel IEG that
      is transiently expressed in the male silkmoth Bombyx mori by female odor
      stimulation. Using Hr38 expression as an indicator of neural activity, we mapped
      comprehensive activity patterns of the silkmoth brain in response to female sex
      pheromones. We found that Hr38 can also be used as a neural activity marker in
      the fly Drosophila melanogaster. Using Hr38, we constructed a neural activity map
      of the fly brain that partially overlaps with fruitless (fru)-expressing neurons
      in response to female stimulation. These findings indicate that Hr38 is a novel
      and conserved insect neural activity marker gene that will be useful for a wide
      variety of neuroethologic studies. 

PMID- 24120641
TI  - Dip1 defines a class of Arp2/3 complex activators that function without preformed
      actin filaments.
AB  - BACKGROUND: Arp2/3 complex is a key actin cytoskeletal regulator that creates
      branched actin filament networks in response to cellular signals. WASP-activated
      Arp2/3 complex assembles branched actin networks by nucleating new filaments from
      the sides of pre-existing ones. WASP-mediated activation requires seed filaments,
      to which the WASP-bound Arp2/3 complex can bind to form branches, but the source
      of the first substrate filaments for branching is unknown. RESULTS: Here we show
      that Dip1, a member of the WISH/DIP/SPIN90 family of actin regulators, potently
      activates Arp2/3 complex without preformed filaments. Unlike other Arp2/3 complex
      activators, Dip1 does not bind actin monomers or filaments, and it interacts with
      the complex using a non-WASP-like binding mode. In addition, Dip1-activated
      Arp2/3 complex creates linear instead of branched actin filament networks.
      CONCLUSIONS: Our data show the mechanism by which Dip1 and other WISH/DIP/SPIN90
      proteins can provide seed filaments to Arp2/3 complex to serve as master switches
      in initiating branched actin assembly. This mechanism is distinct from other
      known activators of Arp2/3 complex.

PMID- 24120642
TI  - Cytokinin induces cell division in the quiescent center of the Arabidopsis root
      apical meristem.
AB  - BACKGROUND: In the root apical meristem, which contains the stem cells that feed
      into root development, the phytohormones auxin and cytokinin play opposing roles,
      with auxin promoting cell division and cytokinin promoting cell differentiation.
      Cytokinin acts in the root tip in part by modulating auxin transport through
      regulation of the level of the PIN auxin efflux carriers. Auxin plays a key role
      in the specification of the quiescent center (QC), which is essential for
      maintaining the stem cell fate of the surrounding cells. RESULTS: We demonstrate
      that cytokinin promotes cell division in the QC, which is generally mitotically
      inactive. Cytokinin downregulates the expression of several key regulatory genes
      in the root tip, including SCARECROW, WOX5, and the auxin influx carriers AUX1
      and LAX2. The decrease in LAX2 expression in response to cytokinin requires ARR1
      and ARR12, two type B ARRs that mediate the primary transcriptional response to
      cytokinin. ARR1 was found to bind directly to the LAX2 gene in vivo, which
      indicates that type B ARRs directly regulate genes that are repressed by
      cytokinin. Disruption of the LAX2 gene results in a phenotype similar to that
      observed in response to cytokinin, including increased division of the cells in
      the QC and decreased expression of WOX5 and the auxin response reporter DR5.
      CONCLUSIONS: Cytokinin acts to regulate auxin distribution in the root apical
      meristem by regulating both the PINs and LAX2. This redistribution of auxin,
      potentially coupled with other auxin-independent effects of cytokinin, regulates
      the mitotic activity in the QC.

PMID- 24120643
TI  - Mathematical anxiety effects on simple arithmetic processing efficiency: an event
      related potential study.
AB  - This study uses event-related brain potentials to investigate the difficulties
      that high math anxious individuals face when processing dramatically incorrect
      solutions to simple arithmetical problems. To this end, thirteen high math
      anxious (HMA) and thirteen low math-anxious (LMA) individuals were presented with
      simple addition problems in a verification task. The proposed solution could be
      correct, incorrect but very close to the correct one (small-split), or
      dramatically incorrect (large-split). The two groups did not differ in
      mathematical ability or trait anxiety. We reproduced previous results for flawed
      scores suggesting HMA difficulties in processing large-split solutions. Moreover,
      large-split solutions elicited a late positive component (P600/P3b) which was
      more enhanced and delayed in the HMA group. Our study proposes that the pattern
      of flawed scores found by previous studies (and that we replicate) has to do with
      HMA individuals'difficulties in inhibiting an extended processing of irrelevant
      information (large-split solutions). 

PMID- 24120644
TI  - Impulsivity and alcohol-related risk among college students: examining urgency,
      sensation seeking and the moderating influence of beliefs about alcohol's role in
      the college experience.
AB  - The personality trait of impulsivity is predictive of heavy drinking and
      consequences among college students. The current study examined how impulsivity
      measured via positive urgency, negative urgency, and sensation seeking-and a
      person's beliefs about the role alcohol plays in the college experience relate to
      drinking and consequences in a sample of 470 college students (mean age=19 years,
      61.3% female, 59.8% White). In support of the hypotheses, sensation seeking
      independently predicted greater drinking, and both positive urgency and negative
      urgency predicted greater experience of alcohol-related negative consequences
      after controlling for consumption level. Moreover, alcohol beliefs moderated the
      relationship between impulsivity types and alcohol outcomes. Among students high
      (versus low) in sensation seeking, strong beliefs about alcohol's role in college
      life were related to significantly greater drinking, and among students high
      (versus low) in negative urgency, endorsing strong beliefs about alcohol's role
      in college life were related to greater levels of alcohol-related negative
      consequences. Overall, findings inform college prevention efforts by highlighting
      the need to distinguish unique facets of impulsivity and examine how they
      intersect with students' beliefs about alcohol in college.

PMID- 24120645
TI  - Assessment of system dysfunction in the brain through MRI-based connectomics.
AB  - Network-based analysis of structural and functional connections has provided a
      new technique to study the brains of healthy people and patients with
      neurological and psychiatric disorders. Graph theory provides a powerful method
      to quantitatively describe the topological organisation of brain connectivity.
      With such a framework, the brain can be depicted as a set of nodes connected by
      edges. Distinct modifications of network topological organisation in the brain
      have been identified during development and normal ageing, whereas disrupted
      functional and structural connectivities have been associated with several
      neurological and psychiatric disorders, including dementia, amyotrophic lateral
      sclerosis, multiple sclerosis, and schizophrenia. These assessments have improved
      understanding of the clinical manifestations noted in these patients, including
      disability and cognitive impairment. Future network-based research might enable
      indentification of different stages of disorders, subtypes for cognitive
      impairment, and connectivity profiles associated with different clinical
      outcomes. 

PMID- 24120646
TI  - Cortactin mediates elevated shear stress-induced mucin hypersecretion via actin
      polymerization in human airway epithelial cells.
AB  - Mucus hypersecretion is a remarkable pathophysiological manifestation in airway
      obstructive diseases. These diseases are usually accompanied with elevated shear
      stress due to bronchoconstriction. Previous studies have reported that shear
      stress induces mucin5AC (MUC5AC) secretion via actin polymerization in cultured
      nasal epithelial cells. Furthermore, it is well known that cortactin, an actin
      binding protein, is a central mediator of actin polymerization. Therefore, we
      hypothesized that cortactin participates in MUC5AC hypersecretion induced by
      elevated shear stress via actin polymerization in cultured human airway
      epithelial cells. Compared with the relevant control groups, Src phosphorylation,
      cortactin phosphorylation, actin polymerization and MUC5AC secretion were
      significantly increased after exposure to elevated shear stress. Similar effects
      were found when pretreating the cells with jasplakinolide, and transfecting with
      wild-type cortactin. However, these effects were significantly attenuated by
      pretreating with Src inhibitor, cytochalasin D or transfecting cells with the
      specific small interfering RNA of cortactin. Collectively, these results suggest
      that elevated shear stress induces MUC5AC hypersecretion via tyrosine
      phosphorylated cortactin-associated actin polymerization in cultured human airway
      epithelial cells. 

PMID- 24120648
TI  - WITHDRAWN: miR-504 affects the radio-resistance in nasopharyngeal carcinoma by
      down-regulating the expression of nuclear respiratory factor 1.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24120647
TI  - CD46: the 'multitasker' of complement proteins.
AB  - Complement is undeniably quintessential for innate immunity by detecting and
      eliminating infectious microorganisms. Recent work, however, highlights an
      equally profound impact of complement on the induction and regulation of a wide
      range of immune cells. In particular, the complement regulator CD46 emerges as a
      key sensor of immune activation and a vital modulator of adaptive immunity. In
      this review, we summarize the current knowledge of CD46-mediated signalling
      events and their functional consequences on immune-competent cells with a
      specific focus on those in CD4(+) T cells. We will also discuss the promises and
      challenges that potential therapeutic modulation of CD46 may hold and pose. 

PMID- 24120649
TI  - Monosialic ganglioside GM3 specifically suppresses the monocyte adhesion to
      endothelial cells for inflammation.
AB  - Vascular endothelial growth factor (VEGF) is well known as a significant
      angiogenic factor, and also functions as a proinflammatory cytokine, which
      induces adhesion of leukocyte to endothelial cells in inflammation reaction. In
      this study, we show that ganglioside GM3 inhibits the VEGF-induced expression of
      intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) through activation of nuclear factor-kappaB (NF-kappaB) via protein
      kinase B (AKT) signaling in human umbilical vein endothelial cells (HUVECs),
      relating with leukocyte recruitment to endothelial cells under inflammatory
      conditions. In addition, ganglioside GM3 significantly reduced the monocyte
      adhesion to HUVECs as determined by the monolayer cell adhesion assay.
      Furthermore, in VEGF-injected mice for the inflammatory condition, ganglioside
      GM3 markedly decreased the expression of ICAM-1 and VCAM-1 in vein tissues. These
      results suggest that ganglioside GM3 has an anti-inflammatory role by suppressing
      the expression of inflammatory-related molecules during in vitro and in vivo
      inflammation. 

PMID- 24120650
TI  - Clinical, electrophysiological, imaging, and ultrastructural description in 68
      patients with neuronal ceroid lipofuscinoses and its subtypes.
AB  - PURPOSE: We evaluated the clinical, electrophysiological, imaging, and
      ultrastructural features of neuronal ceroid lipofuscinoses and its subtypes.
      METHODS: The clinical, electrophysiological, imaging, histopathological, and
      ultrastructural features of 68 (age at onset: 4.3 +/- 5.4 years) neuronal ceroid
      lipofuscinoses and its subtypes (infantile neuronal ceroid lipofuscinoses [9],
      late infantile neuronal ceroid lipofuscinoses [34], juvenile neuronal ceroid
      lipofuscinoses [23], and adult neuronal ceroid lipofuscinoses [2] were evaluated.
      Skin (n = 56), brain (n = 12), muscle (n = 4) and nerve (n = 1) biopsies
      confirmed the diagnosis. RESULTS: Clinical manifestations were milestone
      regression (93%), involuntary movements (92%), seizures (89%), myoclonus (79%),
      and visual impairment (68%). Response to anticonvulsants was unsatisfactory.
      Electroencephalography (n = 59) was abnormal in 90%: background slowing (90%);
      epileptiform discharges (71%), and photoparoxysmal response (4/21). Visual-evoked
      (n = 33) and somatosensory evoked (n = 40) potentials were abnormal in 62% and
      63% of patients. Cranial computed tomography (n = 33) showed diffuse cerebral
      (61%) and cerebellar (27%) atrophy. Magnetic resonance imaging was abnormal in
      all 43 patients who were scanned: diffuse atrophy (100%), cerebellar atrophy
      (40%), leukoencephalopathy (65%), and thalamic T2 W hypointensity (33%). Dermal
      inclusions such as curvilinear inclusions were the most common abnormality: late
      infantile neuronal ceroid lipofuscinoses (97%), juvenile neuronal ceroid
      lipofuscinoses (100%), and infantile neuronal ceroid lipofuscinoses (88%).
      Additional fingerprint inclusions were noted: juvenile neuronal ceroid
      lipofuscinoses (43%), late infantile neuronal ceroid lipofuscinoses (15%), and
      infantile neuronal ceroid lipofuscinoses (13%). Granular osmiophilic deposits
      were noted in 50% of infantile neuronal ceroid lipofuscinoses. In 75% of
      patients, there was good correlation between the clinical subtype and
      ultrastructural inclusion pattern. In 27% of neuronal ceroid lipofuscinoses,
      multiple inclusions were noted. CONCLUSIONS: The diagnosis of neuronal ceroid
      lipofuscinoses should be considered in individuals with characteristic clinical
      presentations and characteristic ultrastructural dermal inclusions. Three fourths
      showed morphological correlation of the inclusions with neuronal ceroid
      lipofuscinoses subtype.

PMID- 24120651
TI  - Molar tooth sign is not pathognomonic for Joubert syndrome.

PMID- 24120652
TI  - Identification of a novel de novo p.Phe932Ile KCNT1 mutation in a patient with
      leukoencephalopathy and severe epilepsy.
AB  - BACKGROUND: More than half of patients with genetic leukoencephalopathies remain
      without a specific diagnosis; this is particularly true in individuals with a
      likely primary neuronal etiology, such as those in which abnormal white matter
      occurs in combination with severe epilepsy. PATIENT: A child with a severe early
      infantile epileptic encephalopathy and abnormal myelination underwent whole exome
      sequencing. RESULTS: Whole exome sequencing identified a heterozygous de novo
      mutation in KCNT1, a sodium-gated potassium channel gene. CONCLUSIONS: Severely
      delayed myelination was anecdotally reported in previous patients with KCNT1
      mutations. This case reinforces that KCNT1 sequencing should be included in an
      investigation of patients with severely delayed myelination and epilepsy.

PMID- 24120653
TI  - A unifying framework for standard and covariate-adaptive randomization procedures
      based on minimizing suitable imbalance functions.
AB  - Minimization is based on minimizing an imbalance function defined in terms of one
      or more covariates. Standard (non-adaptive) randomization procedures, on the
      other hand, generally do not specify or try to minimize an imbalance function.
      However, it turns out that they may be formulated in this manner. Doing so places
      adaptive and standard randomization procedures within the same framework, and
      also suggests novel randomization procedures that combine the best elements of
      both. 

PMID- 24120654
TI  - 25-Methoxylprotopanaxadiol derivatives and their anti-proliferative activities.
AB  - (20R)-25-Methoxyl-dammarane-3beta,12beta,20-triol (25-OCH3-PPD) is a dammarane
      type sapogenin showing anti-proliferative potential. In our study, two series of
      analogs substituted at the C-3 or C-3 and C-12 positions with fatty acids were
      prepared conveniently. The cytotoxic activity of these compounds was evaluated
      using four different human tumor cell lines (A549, Hela, HT-29 and MCF-7) and a
      normal cell line (IOSE144). As compared with 25-OCH3-PPD, compounds 1a, 1b, 2a
      and 2b showed better anti-proliferative activities against all tumor cell lines
      and all the derivatives, with low toxicities in the normal cell line. Compound 1a
      (C-3 monoformiate) exhibited the strongest activity with the IC50 value of 5.2
      MUM towards HT29 cells. The results indicated that the difference in the
      substituents may affect the anti-proliferative activity of the compounds. The
      longer the side chain of 25-OCH3-PPD is, the lower the anti-proliferative
      activity would be. This information may be useful for evaluating the structure
      activity relationship of other dammarane-type sapogenins and for development of
      novel antineoplastic agents.

PMID- 24120655
TI  - Nanotechnology approaches for personalized treatment of multidrug resistant
      cancers.
AB  - The efficacy of chemotherapy is substantially limited by the resistance of cancer
      cells to anticancer drugs that fluctuates significantly in different patients.
      Under identical chemotherapeutic protocols, some patients may receive relatively
      ineffective doses of anticancer agents while other individuals obtain excessive
      amounts of drugs that induce severe adverse side effects on healthy tissues. The
      current review is focused on an individualized selection of drugs and targets to
      suppress multidrug resistance. Such selection is based on the molecular
      characteristics of a tumor from an individual patient that can potentially
      improve the treatment outcome and bring us closer to an era of personalized
      medicine.

PMID- 24120658
TI  - Identification and characterization of platelet alpha2-adrenoceptors and
      imidazoline receptors in rats, rabbits, cats, dogs, cattle, and horses.
AB  - This study aimed to pharmacologically identify and characterize alpha2
      adrenoceptors and imidazoline (I) receptors (I1- and I2-subtype) on canine,
      feline, bovine, equine, murine, and leporine platelet membranes. Saturation
      binding studies with both (3)H-yohimbine and (3)H-clonidine showed that alpha2
      adrenoceptors were expressed on canine, leporine, feline, and murine platelets
      but not on bovine and equine platelets. In competition studies, the rank order of
      affinity of 6 compounds for canine platelet alpha2-adrenoceptors was similar to
      that of potency at alpha2A-subtype reported in human platelets. Saturation
      binding studies in the presence of norepinephrine showed that canine, feline,
      bovine, and equine platelets had I1-receptors defined by (3)H-clonidine binding,
      but neither murine nor leporine platelets had I1-receptors; whereas, platelets of
      all species had I2-receptors defined by (3)H-idazoxan binding. In competition
      studies, more potent compounds displayed biphasic competition curves with (3)H
      clonidine. The rank orders of affinity of I1 compounds for high-affinity
      components of I1-receptors of canine, feline, bovine, and equine platelets and I2
      receptors of all species platelets were similar to those of compounds for high
      affinity components reported in human I1- and I2-receptors, respectively. Guanine
      nucleotides inhibited the high-affinity component of naphazoline binding to
      canine I1-receptors, but not to I2-receptors. Furthermore, guanine nucleotides
      dose-dependently inhibited (3)H-clonidine binding to I1-receptors; whereas, they
      did not interfere with (3)H-idazoxan binding to I2-receptors, supporting the
      notion that Il-receptors may belong to a G protein-coupled receptor superfamily
      in canine platelets. Interspecific variations of platelet alpha2-adrenoceptor and
      imidazoline receptor expressions may explain different platelet responses to
      catecholamines and imidazoline alpha-adrenergic agents. 

PMID- 24120656
TI  - Nanomedicine therapeutic approaches to overcome cancer drug resistance.
AB  - Nanomedicine is an emerging form of therapy that focuses on alternative drug
      delivery and improvement of the treatment efficacy while reducing detrimental
      side effects to normal tissues. Cancer drug resistance is a complicated process
      that involves multiple mechanisms. Here we discuss the major forms of drug
      resistance and the new possibilities that nanomedicines offer to overcome these
      treatment obstacles. Novel nanomedicines that have a high ability for flexible,
      fast drug design and production based on tumor genetic profiles can be created
      making drug selection for personal patient treatment much more intensive and
      effective. This review aims to demonstrate the advantage of the young medical
      science field, nanomedicine, for overcoming cancer drug resistance. With the
      advanced design and alternative mechanisms of drug delivery known for different
      nanodrugs including liposomes, polymer conjugates, micelles, dendrimers, carbon
      based, and metallic nanoparticles, overcoming various forms of multi-drug
      resistance looks promising and opens new horizons for cancer treatment.

PMID- 24120659
TI  - Expression and motor functional roles of voltage-dependent type 7 K(+) channels
      in the human taenia coli.
AB  - Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of
      neurons and muscle cells. The aims of the present study were to investigate the
      motor effects of KV7 channel modulators and the expression of KV7 channels in the
      human taenia coli. The effects of KV7 channel modulators on the muscle tone of
      human taenia coli strips were investigated under nonadrenergic non-nitrergic
      conditions by organ bath studies. Gene expression and tissue localisation of
      channels were studied by real-time PCR and immunohistochemistry, respectively.
      Under basal conditions, the KV7 channel blocker XE-991 induced concentration
      dependent contractions, with mean EC50 and Emax of 18.7 MUM and 30.5%
      respectively of the maximal bethanechol-induced contraction, respectively. The
      KV7 channel activators retigabine and flupirtine concentration-dependently
      relaxed the taenia coli, with mean EC50s of 19.2 MUM and 29.9 MUM, respectively.
      Retigabine also relaxed bethanechol-precontracted strips, with maximal
      relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects
      induced by the KV7 channel modulators were not affected by tetrodotoxin or omega
      conotoxin GVIA. XE-991 greatly reduced retigabine- and flupirtine-induced
      relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia
      coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were
      clearly visualised by immunohistochemistry in colonic epithelium, circular muscle
      layer and taenia coli. KV7 channels appear to contribute to the resting muscle
      tone of the human taenia coli. In addition, KV7 channel activators significantly
      relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for
      colonic motor disorders.

PMID- 24120660
TI  - Sphingosine-1-phosphate induced contraction of bladder smooth muscle.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most
      smooth muscles. Although S1P has been shown to contract bladder smooth muscle,
      the mechanism(s) by which S1P initiates contraction has not been extensively
      investigated. The goal of this study was to determine if S1P-induced force
      generation and myosin light chain (MLC) phosphorylation are dependent on calcium
      sensitization pathways mediated by protein kinase C (PKC) and Rho kinase (ROCK)
      and which S1P receptor is important in this response. Bladder smooth muscle
      strips from rabbit and rat were mounted for isometric force recording and
      contracted in response to carbachol or S1P in the presence and absence of an
      inhibitor of PKC (3 uM Bisindolylmaleimide-1) or ROCK (1 uM H-1172). 10 uM S1P
      produced approximately 40% of the force generated in response to 110 mM KCl in
      rabbit bladder smooth muscle. S1P, up to 100 uM, did not produce a response in
      rat bladder smooth muscle, any response evoked was due to solvent (NaOH). S1P
      dependent force development was associated with a concomitant increase in
      Ser(19), but not dual Thr(18)/Ser(19) MLC phosphorylation. Inhibition of PKC
      decreased force development, whereas inhibition of ROCK abolished S1P-induced
      force. An inhibitor of the S1P2 receptor, JTE-013, relaxed a S1P-induced
      contraction; whereas, an agonist with low affinity to the S1P2 receptor, dihydro
      S1P, did not elicit a contraction. Our results suggest that S1P contracts rabbit,
      but not rat, bladder smooth muscle via the S1P2 receptor and is dependent on MLC
      phosphorylation and myofilament calcium sensitization primarily in response to
      ROCK activation.

PMID- 24120657
TI  - Can nanomedicines kill cancer stem cells?
AB  - Most tumors are heterogeneous and many cancers contain small population of highly
      tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like
      normal stem cell, CSCs have the ability to self-renew and differentiate to other
      tumor cell types. They are believed to be a source for drug resistance, tumor
      recurrence and metastasis. CSCs often overexpress drug efflux transporters, spend
      most of their time in non-dividing G0 cell cycle state, and therefore, can escape
      the conventional chemotherapies. Thus, targeting CSCs is essential for developing
      novel therapies to prevent cancer relapse and emerging of drug resistance.
      Nanocarrier-based therapeutic agents (nanomedicines) have been used to achieve
      longer circulation times, better stability and bioavailability over current
      therapeutics. Recently, some groups have successfully applied nanomedicines to
      target CSCs to eliminate the tumor and prevent its recurrence. These approaches
      include 1) delivery of therapeutic agents (small molecules, siRNA, antibodies)
      that affect embryonic signaling pathways implicated in self-renewal and
      differentiation in CSCs, 2) inhibiting drug efflux transporters in an attempt to
      sensitize CSCs to therapy, 3) targeting metabolism in CSCs through nanoformulated
      chemicals and field-responsive magnetic nanoparticles and carbon nanotubes, and
      4) disruption of multiple pathways in drug resistant cells using combination of
      chemotherapeutic drugs with amphiphilic Pluronic block copolymers. Despite clear
      progress of these studies the challenges of targeting CSCs by nanomedicines still
      exist and leave plenty of room for improvement and development. This review
      summarizes biological processes that are related to CSCs, overviews the current
      state of anti-CSCs therapies, and discusses state-of-the-art nanomedicine
      approaches developed to kill CSCs.

PMID- 24120661
TI  - Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein
      kinase activity and nuclear localization.
AB  - Alternative splicing of the PKM2 gene produces two isoforms, M1 and M2, which are
      preferentially expressed in adult and embryonic tissues, respectively. The M2
      isoform is reexpressed in human cancer and has nonmetabolic functions in the
      nucleus as a protein kinase. Here, we report that PKM2 is acetylated by p300
      acetyltransferase at K433, which is unique to PKM2 and directly contacts its
      allosteric activator, fructose 1,6-bisphosphate (FBP). Acetylation prevents PKM2
      activation by interfering with FBP binding and promotes the nuclear accumulation
      and protein kinase activity of PKM2. Acetylation-mimetic PKM2(K433) mutant
      promotes cell proliferation and tumorigenesis. K433 acetylation is decreased by
      serum starvation and cell-cell contact, increased by cell cycle stimulation,
      epidermal growth factor (EGF), and oncoprotein E7, and enriched in breast
      cancers. Hence, K433 acetylation links cell proliferation and transformation to
      the switch of PKM2 from a cytoplasmic metabolite kinase to a nuclear protein
      kinase. 

PMID- 24120662
TI  - Structural basis of mRNA recognition and cleavage by toxin MazF and its
      regulation by antitoxin MazE in Bacillus subtilis.
AB  - MazF is an mRNA interferase, which, upon activation during stress conditions,
      cleaves mRNAs in a sequence-specific manner, resulting in cellular growth arrest.
      During normal growth conditions, the MazF toxin is inactivated through binding to
      its cognate antitoxin, MazE. How MazF specifically recognizes its mRNA target and
      carries out cleavage and how the formation of the MazE-MazF complex inactivates
      MazF remain unclear. We present crystal structures of MazF in complex with mRNA
      substrate and antitoxin MazE in Bacillus subtilis. The structure of MazF in
      complex with uncleavable UUdUACAUAA RNA substrate defines the molecular basis
      underlying the sequence-specific recognition of UACAU and the role of residues
      involved in the cleavage through site-specific mutational studies. The structure
      of the heterohexameric (MazF)2-(MazE)2-(MazF)2 complex in Bacillus subtilis,
      supplemented by mutational data, demonstrates that the positioning of the C
      terminal helical segment of MazE within the RNA-binding channel of the MazF dimer
      prevents mRNA binding and cleavage by MazF. 

PMID- 24120663
TI  - The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome
      separation.
AB  - Cytokinesis follows separase activation and chromosome segregation. This order is
      ensured in budding yeast by the mitotic exit network (MEN), where Cdc14p
      dephosphorylates key conserved Cdk1-substrates exemplified by the anaphase
      spindle-elongation protein Ase1p. However, in metazoans, MEN and Cdc14 function
      is not conserved. Instead, the PP2A-B55alpha/ENSA/Greatwall (BEG) pathway
      controls the human Ase1p ortholog PRC1. In this pathway, PP2A-B55 inhibition is
      coupled to Cdk1-cyclin B activity, whereas separase inhibition is maintained by
      cyclin B concentration. This creates two cyclin B thresholds during mitotic exit.
      Simulation and experiments using PRC1 as a model substrate show that the first
      threshold permits separase activation and chromosome segregation, and the second
      permits PP2A-B55 activation and initiation of cytokinesis. Removal of the
      ENSA/Greatwall (EG) timer module eliminates this second threshold, as well as
      associated delay in PRC1 dephosphorylation and initiation of cytokinesis, by
      uncoupling PP2A-B55 from Cdk1-cyclin B activity. Therefore, temporal order during
      mitotic exit is promoted by the metazoan BEG pathway. 

PMID- 24120664
TI  - Context-dependent wiring of Sox2 regulatory networks for self-renewal of
      embryonic and trophoblast stem cells.
AB  - Sox2 is a transcription factor required for the maintenance of pluripotency. It
      also plays an essential role in different types of multipotent stem cells,
      raising the possibility that Sox2 governs the common stemness phenotype. Here we
      show that Sox2 is a critical downstream target of fibroblast growth factor (FGF)
      signaling, which mediates self-renewal of trophoblast stem cells (TSCs).
      Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF
      dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem
      cells (ESCs) and TSCs combined with inducible knockout systems, we found that,
      despite the common role in safeguarding the stem cell state, Sox2 regulates
      distinct sets of genes with unique functions in these two different yet
      developmentally related types of stem cells. Our findings provide insights into
      the functional versatility of transcription factors during embryogenesis, during
      which they can be recursively utilized in a variable manner within discrete
      network structures.

PMID- 24120665
TI  - The translational landscape of the mammalian cell cycle.
AB  - Gene regulation during cell-cycle progression is an intricately choreographed
      process, ensuring accurate DNA replication and division. However, the
      translational landscape of gene expression underlying cell-cycle progression
      remains largely unknown. Employing genome-wide ribosome profiling, we uncover
      widespread translational regulation of hundreds of mRNAs serving as an unexpected
      mechanism for gene regulation underlying cell-cycle progression. A striking
      example is the S phase translational regulation of RICTOR, which is associated
      with cell cycle-dependent activation of mammalian target of rapamycin complex 2
      (mTORC2) signaling and accurate cell-cycle progression. We further identified
      unappreciated coordination in translational control of mRNAs within molecular
      complexes dedicated to cell-cycle progression, lipid metabolism, and genome
      integrity. This includes the majority of mRNAs comprising the cohesin and
      condensin complexes responsible for maintaining genome organization, which are
      coordinately translated during specific cell cycle phases via their 5' UTRs. Our
      findings illuminate the prevalence and dynamic nature of translational regulation
      underlying the mammalian cell cycle. 

PMID- 24120666
TI  - The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis.
AB  - The DNA damage response (DDR) is activated by oncogenic stress, but the
      mechanisms by which this occurs, and the particular DDR functions that constitute
      barriers to tumorigenesis, remain unclear. We established a mouse model of
      sporadic oncogene-driven breast tumorigenesis in a series of mutant mouse strains
      with specific DDR deficiencies to reveal a role for the Mre11 complex in the
      response to oncogene activation. We demonstrate that an Mre11-mediated DDR
      restrains mammary hyperplasia by effecting an oncogene-induced G2 arrest.
      Impairment of Mre11 complex functions promotes the progression of mammary
      hyperplasias into invasive and metastatic breast cancers, which are often
      associated with secondary inactivation of the Ink4a-Arf (CDKN2a) locus. These
      findings provide insight into the mechanism of DDR engagement by activated
      oncogenes and highlight genetic interactions between the DDR and Ink4a-Arf
      pathways in suppression of oncogene-driven tumorigenesis and metastasis. 

PMID- 24120667
TI  - HDAC5, a key component in temporal regulation of p53-mediated transactivation in
      response to genotoxic stress.
AB  - Despite being one of the most well-studied transcription factors, the temporal
      regulation of p53-mediated transcription is not very well understood. Recent data
      suggest that target specificity of p53-mediated transactivation is achieved by
      posttranslational modifications of p53. K120 acetylation is a modification
      critical for recruitment of p53 to proapoptotic targets. Our data reveal that
      histone deacetylase 5 (HDAC5) binds to p53 and abrogates K120 acetylation,
      resulting in preferential recruitment of p53 to proarrest and antioxidant targets
      at early phases of stress. However, upon prolonged genotoxic stress, HDAC5
      undergoes nuclear export. Concomitantly, p53 is acetylated at the K120 residue
      and selectively transactivates proapoptotic target genes, leading to onset of
      apoptosis. Furthermore, upon genotoxic stress in mice where HDAC5 expression is
      downregulated, the onset of apoptosis is accelerated in the highly vulnerable
      tissues. These findings suggest that HDAC5 is a key determinant of p53-mediated
      cell fate decisions in response to genotoxic stress. 

PMID- 24120668
TI  - Bisphosphonate therapy for unresectable symptomatic benign bone tumors: a long
      term prospective study of tolerance and efficacy.
AB  - OBJECTIVES: To evaluate the long-term tolerance of bisphosphonates proposed as an
      alternative therapeutic option for symptomatic unresectable benign bone tumors
      and to evaluate the long-term efficacy of this treatment. METHODS: From March
      2007 to March 2011, patients with unresectable symptomatic benign bone tumors
      were consecutively included in this institutional review board-approved study and
      treated with bisphosphonates. Prospectively long-term follow-up is reported. The
      study endpoints were to describe the long-term tolerance, the clinical evolution
      of pain for each patient and the radiological success defined as a complete
      disappearance of inflammation and ossification of the bone lesion. All
      complications and side effects were recorded. RESULTS: Eight patients (mean age
      16 years; range 7-42) with various tumor subtypes were included: aneurysmal bone
      cysts (N=5), Langerhans cell histiocytosis (N=1), osteoblastoma (N=1), and a
      giant cell tumor (N=1). Tumors were located in cervical (N=4) or thoracic (N=1)
      vertebrae, femoral shaft (N=1), acetabulum (N=1) and sacrum (N=1). Mean number of
      bisphosphonate cycles was 3 (range: 1-6) over a median period of 10 months. The
      median clinical and imaging follow-up period was 21 months (6 to 63 months). No
      severe complications due to treatment or lesion recurrence were reported. Pain
      disappeared within 6 weeks of the first cycle for all but one patient.
      Ossification of the bone lesion was observed for all patients but one, complete
      for two and partial for the five others. CONCLUSIONS: Bisphosphonates appear to
      be an effective option without adverse effects for the non-operative management
      of symptomatic benign bone tumors.

PMID- 24120670
TI  - Urinary neutrophil gelatinase-associated lipocalin for early detection of acute
      kidney injury in geriatric patients with urinary tract infection treated by
      colistin.
AB  - INTRODUCTION: Colistin (polymyxin E) was developed ~ 60 years ago but was rarely
      used in clinical practice during the last 20 years because of concerns related to
      high rates of nephrotoxicity. However, it was recently reintroduced to clinical
      practice in many parts of the world for the treatment of multi-drug resistant
      gram-negative bacilli. In the current study, we evaluated the predictive capacity
      of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of
      acute kidney injury (AKI) in geriatric patients with urinary tract infection
      (UTI) receiving colistin therapy. METHODS: We studied 116 patients aged 80.7 +/-
      12 treated with colistin who suffered from UTI. Urinary NGAL was measured at
      baseline and 1 - 2 hours after the second dose of colistin. The primary outcome
      was AKI. Secondary outcome was in-hospital morbidity and mortality. RESULTS: 52
      patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had
      underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without
      changes in renal function during hospitalization and the remaining 48 patients
      (41%) had normal kidney function. The mean duration of colistin therapy was 9.1
      +/- 4.8 days. At baseline, urine NGAL was 405 +/- 452 g/l in ATN, 285 +/- 256 g/l
      in prerenal azotemia, 390 +/- 468 g/l in CKD and 347 +/- 877 g/l in normal kidney
      function patients (difference non-significant). We were unable to demonstrate
      statistically significant increments of urine NGAL following colistin
      administration in either ATN or non-ATN patient groups. Urine NGAL was not
      correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities
      such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver
      operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity
      0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar
      results were obtained for secondary outcomes. CONCLUSIONS: Our data suggest
      limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large
      clinical setting of geriatric patients hospitalized for UTI and receiving the
      potentially nephrotoxic colistin. This finding is likely due to the powerful
      influence of UTI on NGAL levels in both patients with normal kidney function and
      those with a wide spectrum of acute or chronic kidney diseases.

PMID- 24120671
TI  - Family history of immigration from a tuberculosis endemic country and low family
      income are associated with a higher BCG vaccination coverage in Ile-de-France
      region, France.
AB  - After withdrawal of multipuncture BCG device from the French market in January
      2006, vaccination coverage (VC) with the intradermal device has dropped and since
      remained sub-optimal in Ile-de-France, the only region of mainland France where
      BCG is recommended to all children. We conducted a cross-sectional study to
      identify socio-economic factors associated with BCG VC in children of Paris
      metropolitan area born after January 2006. Two-stage random sampling was used to
      include 425 children up to 5 years old from Paris and its suburbs. Information
      was collected through face-to-face interviews and vaccination status confirmed by
      a vaccination document. Poisson regression analyzed the association between VC
      and potential determinants. VC of children from families with the lowest incomes
      (first quartile of family income/consumption unit (CU) (<883 ?) was close to 100%
      regardless of family origin. In families with higher incomes (>= 883 ?/CU), VC
      was significantly higher among children born to families from a tuberculosis
      highly endemic country (98.2%) compared with other children (76.2%) (p=0.004).
      Children of low socio-economic background as well as those with a family history
      of immigration, regardless of family income, are correctly identified as being at
      high risk of tuberculosis and properly vaccinated with BCG in this area.

PMID- 24120672
TI  - Immunogenicity and safety of Fluzone((r)) intradermal and high-dose influenza
      vaccines in older adults >=65 years of age: a randomized, controlled, phase II
      trial.
AB  - We conducted a randomized, controlled, multicenter, phase II study to evaluate
      the immunogenicity and safety of an investigational intradermal (ID) trivalent
      influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older
      adults (>=65 years of age). Older adult subjects were immunized with ID vaccine
      containing either 15MUg hemagglutinin (HA)/strain (n=636) or 21MUg HA/strain
      (n=634), with HD IM vaccine containing 60MUg HA/strain (n=320), or with standard
      dose (SD) IM vaccine (Fluzone((r)); 15MUg HA/strain; n=319). For comparison,
      younger adults (18-49 years of age) were immunized with SD IM vaccine. In older
      adults, post-vaccination geometric mean titers induced by the ID vaccines were
      superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains
      and non-inferior for the B strain. Seroconversion rates induced by the ID
      vaccines were superior to those induced by the SD IM vaccine in older adults for
      the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not
      differ significantly for the two ID vaccine dosages. Post-vaccination geometric
      mean titers, seroconversion rates, and most seroprotection rates were
      significantly higher in HD vaccine recipients than in older adult recipients of
      the SD IM or ID vaccines and, for most measures, were comparable to those of
      younger adult SD IM vaccine recipients. Injection-site reactions, but not
      systemic reactions or unsolicited adverse events, were more common with the ID
      vaccines than with the IM vaccines. No treatment-related serious adverse events
      were reported. This study demonstrated that: (1) the ID and HD vaccines were well
      tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD
      vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD
      vaccine in older adults and the SD IM vaccine in younger adults elicited
      comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).

PMID- 24120669
TI  - Osteoblastic cell secretome: a novel role for progranulin during risedronate
      treatment.
AB  - It is well established that osteoblasts, the key cells involved in bone formation
      during development and in adult life, secrete a number of glycoproteins harboring
      autocrine and paracrine functions. Thus, investigating the osteoblastic secretome
      could yield important information for the pathophysiology of bone. In the present
      study, we characterized for the first time the secretome of human Hobit
      osteoblastic cells. We discovered that the secretome comprised 89 protein species
      including the powerful growth factor progranulin. Recombinant human progranulin
      (6nM) induced phosphorylation of mitogen-activated protein kinase in both Hobit
      and osteocytic cells and induced cell proliferation and survival. Notably,
      risedronate, a nitrogen-containing bisphosphonate widely used in the treatment of
      osteoporosis, induced the expression and secretion of progranulin in the Hobit
      secretome. In addition, our proteomic study of the Hobit secretome revealed that
      risedronate induced the expression of ERp57, HSP60 and HSC70, three proteins
      already shown to be associated with the prevention of bone loss in osteoporosis.
      Collectively, our findings unveil novel targets of risedronate-evoked biological
      effects on osteoblast-like cells and further our understanding of the mechanisms
      of action of this currently used compound. 

PMID- 24120673
TI  - Alanine scanning of the rabies virus glycoprotein antigenic site III using
      recombinant rabies virus: implication for post-exposure treatment.
AB  - The safety and availability of the human polyclonal sera that is currently
      utilized for post-exposure treatment (PET) of rabies virus (RABV) infection
      remain a concern. Recombinant monoclonal antibodies have been postulated as
      suitable alternatives by WHO. To this extent, CL184, the RABV human antibody
      combination comprising monoclonal antibodies (mAbs) CR57 and CR4098, has been
      developed and has delivered promising clinical data to support its use for RABV
      PET. For this fully human IgG1 cocktail, mAbs CR57 and CR4098 are produced in the
      PER.C6 human cell line and combined in equal amounts in the final product. During
      preclinical evaluation, CR57 was shown to bind to antigenic site I whereas CR4098
      neutralization was influenced by a mutation of position 336 (N336) located within
      antigenic site III. Here, alanine scanning was used to analyze the influence of
      mutations within the potential binding site for CR4098, antigenic site III, in
      order to evaluate the possibility of mutated rabies viruses escaping
      neutralization. For this approach, twenty flanking amino acids (10 upstream and
      10 downstream) of the RABV glycoprotein (G) asparagine (N336) were exchanged to
      alanine (or serine, if already alanine) by site-directed mutagenesis. Analysis of
      G expression revealed four of the twenty mutant Gs to be non-functional, as shown
      by their lack of cell surface expression, which is a requirement for the
      production of infectious RABV. Therefore, these mutants were excluded from
      further study. The remaining sixteen mutants were introduced in an infectious
      clone of RABV, and recombinant RABVs (rRABVs) were recovered and utilized for in
      vitro neutralization assays. All of the viruses were effectively neutralized by
      CR4098 as well as by CR57, indicating that single amino acid exchanges in this
      region does not affect the broad neutralizing capability of the CL184 mAb
      combination. 

PMID- 24120675
TI  - TLR4 ligand formulation causes distinct effects on antigen-specific cell-mediated
      and humoral immune responses.
AB  - The formulation of TLR ligands and other immunomodulators has a critical effect
      on their vaccine adjuvant activity. In this work, the synthetic TLR4 ligand GLA
      was formulated with three distinct vaccine delivery system platforms (aqueous
      suspension, liposome, or oil-in-water emulsion). The effect of the different
      formulations on the adaptive immune response to protein subunit vaccines was
      evaluated in the context of a recombinant malaria antigen, Plasmodium berghei
      circumsporozoite protein (PbCSP). Antibody responses in vaccinated mice were
      similar for the different formulations of GLA. However, cell-mediated responses
      differed significantly depending on the adjuvant system; in particular, the
      emulsion formulation of the TLR4 ligand induced significantly enhanced cellular
      IFN-gamma and TNF-alpha responses compared to the other formulations. The effects
      of differences in adjuvant formulation composition and physical characteristics
      on biological activity are discussed. These results illustrate the importance of
      formulation of immunostimulatory adjuvants (e.g. TLR ligands) on the resulting
      immune responses to adjuvanted vaccines and may play a critical role for
      combating diseases where T cell immunity is advantageous. 

PMID- 24120674
TI  - High throughput quantification of capsular polysaccharides for multivalent
      vaccines using precipitation with a cationic surfactant.
AB  - The increasing requirement for multivalent vaccines containing diverse capsular
      polysaccharides has created an unmet need for a fast and straightforward assay
      for polysaccharide titer. We describe a novel and robust assay for the
      quantitation of anionic capsular polysaccharides. The binding of
      hexadecyltrimethyammonium bromide (Hb) to anionic capsular polysaccharides
      results in a precipitation reaction wherein the suspension turbidity is
      proportional to polysaccharide titer. The turbidity can be quickly measured as
      absorbance across a range of wavelengths that resolve scattering light.
      Carbohydrates comprised of repeating units of one to seven monosaccharides with
      phosphodiester groups, uronic acids, and sialic acids all reacted strongly and
      there does not appear to be specificity with respect to the particular anionic
      moiety. The assay is compatible with an array of common buffers across a pH range
      of 3.0-8.75 and with NaCl concentration exceeding 400 mM. Interference from DNA
      can be eliminated with a short incubation step with DNase. With these treatments,
      the assay has been employed in samples as complex as fermentation broth. A two
      log dynamic range has been established with a mean relative standard deviation
      less than 10% across this range although inferior performance has been observed
      in fermentation broth. The precipitation assay enables the rapid quantitation of
      anionic polysaccharides. The resulting procedure can robustly measure the titer
      of myriad anionic capsular polysaccharides (CPS) in 96 samples in less than 30
      min using low toxicity reagents and routine laboratory equipment. This
      development will greatly reduce the effort required to measure polysaccharide
      titer and yield during process development of polysaccharide vaccines.

PMID- 24120676
TI  - Vaccination of health care workers against influenza: is it time to think about a
      mandatory policy in Europe?
AB  - Nosocomial influenza outbreaks and the transmission of influenza to health care
      workers (HCWs) have been well described. However, vaccine coverage among HCWs
      still remains low. After three decades of official recommendations that all HCWs
      be vaccinated against influenza, vaccination rates generally remain below 30% in
      Europe. Experiences in the USA have shown that mandatory policies achieve a
      compliance rate of nearly 100%. However, the discussion about mandatory
      vaccination policies for HCWs has not advanced very far in Europe. This article
      therefore discusses the question whether it is time to consider mandatory
      vaccination policies for HCWs in Europe. We further elaborate under which
      conditions mandatory vaccination polices would be ethically justified and how far
      these conditions are met in the case of influenza vaccination of HCWs. From a
      methodological perspective, it would be desirable to have further high-quality
      RCTs with a lower risk of bias that investigate the effectiveness of HCWs
      influenza vaccination. From a policy perspective, however, we have to decide
      whether we have already sufficient (albeit not perfect) evidence to justify
      mandatory influenza vaccination programs for HCWs. We conclude: Given the
      available evidence concerning the benefits, burdens and risks of HCWs influenza
      vaccination and the limited effectiveness of voluntary policies, it is time to
      consider mandatory vaccination policies for HCWs in Europe. 

PMID- 24120677
TI  - Impact of maternal characteristics on the effect of maternal influenza
      vaccination on fetal outcomes.
AB  - BACKGROUND: Maternal infections during pregnancy have been associated with
      adverse fetal and infant health outcomes, and vaccination against influenza is
      the most effective tool to prevent morbidity and mortality due to seasonal and
      pandemic influenza. We evaluated the association between receipt of the
      inactivated seasonal influenza vaccine on preterm and small for gestational age
      (SGA) births, with the aim to assess racial and socioeconomic variations in
      vaccine effect. METHODS: We conducted a retrospective analysis of state-wide
      surveillance data from Georgia for the most recent four years available at the
      beginning of the study, a total of 8393 live births in Georgia from January 1,
      2005 through December 31, 2008. We constructed multivariable logistic regression
      models and calculated odds ratios (OR) estimates with corresponding 95%
      confidence intervals (CI) to evaluate the effect of maternal influenza
      vaccination on SGA (birth weight <10th percentile for gestational age) and
      preterm (gestational age at birth <37 weeks) births while controlling for
      potential confounders. RESULTS: Among all women, we found significant strong
      associations between maternal influenza vaccination and reduced odds of a preterm
      birth during the widespread influenza activity period [OR=0.39, 95% CI: 0.18,
      0.83]. In this period, vaccination was protective against SGA births among women
      at higher risk for influenza related morbidity - women enrolled in the Women,
      Infant and Child (WIC) program [OR=0.20, 95% CI: 0.04, 0.98] and Black women
      [OR=0.15 95% CI: 0.02, 0.94]; maternal influenza vaccination was associated with
      reduced odds of a preterm birth among white women [OR=0.34, 95% CI: 0.12, 0.91]
      and women of higher socio-economic status [OR=0.30, 95% CI: 0.12, 0.74].
      CONCLUSION: Influenza vaccination during pregnancy was significantly associated
      with reduced odds of small for gestational age and preterm births during the
      widespread influenza activity period. Vaccination effects varied by socio
      demographic characteristics.

PMID- 24120678
TI  - Levels and functionality of antibodies after pneumococcal conjugate vaccine in
      schedules with different timing of the booster dose.
AB  - The seven-valent pneumococcal conjugate vaccine (PCV7) has been introduced in
      most high-income countries, although with differences in age, timing and number
      of primary doses before 6 months of age and presence and timing of a booster
      vaccination. The objective was to determine and compare the IgG antibody levels
      and functionality of IgG responses (avidity and opsonophagocytoses) at 1 and 2
      years of age following 2 primary doses with a booster at 11 or 24 months of age.
      Children received PCV7 at 2 and 4 months (2-dose group), or at 2, 4 and 11 months
      (2+1-dose group), or no PCV7 (controls) before 1 year of age. All children
      received a PCV7 dose at 24 months of age. At the age of 12 months, the 2+1-dose
      group had higher IgG levels and functional antibody levels, compared to the 2
      dose group for all serotypes, but at 25 months the difference between the 2-dose
      and 2+1-dose groups had disappeared for most serotypes. The kinetics of
      opsonophagocytic antibodies were in line with the specific IgG antibody levels
      for most serotypes, although differences between the 2-dose and the 2+1-dose
      group were more pronounced in OPA activity as compared to the IgG levels
      especially at the age of 24 months. Delaying the booster dose from 11 months to
      24 months after 2 primary doses resulted in significantly higher OPA GMTs one
      month after the booster dose. This must, however, be balanced against the risk of
      leaving children unboosted between the age of 11 and 24 months at a time when
      disease risk is still high. Local decisions about the timing of a booster dose
      should also take into account vaccine coverage and the indirect herd effect in a
      well vaccinated population. Trial registration clinicaltrials.gov Identifier:
      NCT00189020. 

PMID- 24120679
TI  - Preclinical immunogenicity and functional activity studies of an A+W
      meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing
      meningococcal conjugate- and polysaccharide vaccines.
AB  - Meningococci of serogroups A and W (MenA and MenW) are the main causes of
      epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we
      prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from
      representative African MenA and MenW strains, and compared the immunogenicity of
      this vaccine with existing meningococcal conjugate and polysaccharide (PS)
      vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W
      dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine
      (MenAfriVac((r)), Serum Institute of India), ACYW conjugate vaccine (Menveo((r)),
      Novartis) or ACYW PS vaccine (Mencevax((r)), GlaxoSmithKline). The mice received
      2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune
      responses were tested in ELISA, serum bactericidal activity (SBA) and
      opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against
      both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA
      titers against both MenA and MenW vaccine strains were detected after only one
      dose of the A+W dOMV vaccine, and the titers were further increased after the
      second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were
      significantly higher than in mice immunized with the ACYW-conjugate vaccine or
      the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA
      titers against MenA of the same magnitude as the titers induced by the A
      conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of
      functional antibodies to both MenA and MenW strains, levels that were shown to be
      higher or equal to the levels induced by licensed meningococcal vaccines. Thus,
      an A+W dOMV vaccine could potentially serve as an alternative or a supplement to
      existing conjugate and PS vaccines in the African meningitis belt. 

PMID- 24120680
TI  - Plant heat shock protein 90 as carrier-adjuvant for immunization against a
      reporter antigen.
AB  - Here, we evaluated the modulation of the immune response induced by Hsp90 of
      Nicotiana benthamiana (NbHsp90.3) against the Maltose Binding Protein (MBP) as a
      reporter antigen. Equimolar quantities of recombinant proteins were administered
      in mice as follows: MBP alone (MBP group), a mixture of MBP and rNbHsp90.3
      (MBP+rNbHsp90.3 group) and the fusion of MBP to rNbHsp90.3 (MBP-rNbHsp90.3
      group). The covalent linkage between NbHsp90.3 and MBP to bring a fusion protein
      was essential to induce the strong specific antibody response with predominance
      of IgG2a. Eighty-four days after the first immunization, splenocyte proliferation
      from MBP-rNbHsp90.3-immunized mice was consistently higher than that from MBP and
      MBP+rNbHsp90.3 groups. In addition, splenocytes from MBP-rNbHsp90.3 immunized
      mice produced higher levels of IFN-gamma than controls. Finally, both
      formulations with rNbHsp90.3 significantly enhanced the MHC class I expression
      levels, but only rNbHsp90.3 covalent bound to MBP induced a specific cellular
      immune response against MBP measured as increased percentage of CD8(+) T cells.
      Taken together, these results suggest that plant HSP90s could be incorporated as
      adjuvants in vaccines that require the generation of a Th1 response along with a
      CD8 cytotoxic cell response to confer immunity. 

PMID- 24120682
TI  - Dissection of the ATP-dependent conformational change cycle of a group II
      chaperonin.
AB  - Group II chaperonin captures an unfolded protein while in its open conformation
      and then mediates the folding of the protein during ATP-driven conformational
      change cycle. In this study, we performed kinetic analyses of the group II
      chaperonin from a hyperthermophilic archaeon, Thermococcus sp. KS-1 (TKS1-Cpn),
      by stopped-flow fluorometry and stopped-flow small-angle X-ray scattering to
      reveal the reaction cycle. Two TKS1-Cpn variants containing a Trp residue at
      position 265 or position 56 exhibit nearly the same fluorescence kinetics induced
      by rapid mixing with ATP. Fluorescence started to increase immediately after the
      start of mixing and reached a maximum at 1-2s after mixing. Only in the presence
      of K(+) that a gradual decrease in fluorescence was observed after the initial
      peak. Similar results were obtained by stopped-flow small-angle X-ray scattering.
      A rapid fluorescence increase, which reflects nucleotide binding, was observed
      for the mutant containing a Trp residue near the ATP binding site (K485W),
      irrespective of the presence or absence of K(+). Without K(+), a small, rapid
      fluorescence decrease followed the initial increase, and then a gradual decrease
      was observed. In contrast, with K(+), a large, rapid fluorescence decrease
      occurred just after the initial increase, and then the fluorescence gradually
      increased. Finally, we observed ATP binding signal and also subtle conformational
      change in an ATPase-deficient mutant with K485W mutation. Based on these results,
      we propose a reaction cycle model for group II chaperonins. 

PMID- 24120681
TI  - Insect antiviral innate immunity: pathways, effectors, and connections.
AB  - Insects are infected by a wide array of viruses some of which are insect
      restricted and pathogenic, and some of which are transmitted by biting insects to
      vertebrates. The medical and economic importance of these viruses heightens the
      need to understand the interaction between the infecting pathogen and the insect
      immune system in order to develop transmission interventions. The interaction of
      the virus with the insect host innate immune system plays a critical role in the
      outcome of infection. The major mechanism of antiviral defense is the small,
      interfering RNA pathway that responds through the detection of virus-derived
      double-stranded RNA to suppress virus replication. However, other innate
      antimicrobial pathways such as Imd, Toll, and Jak-STAT and the autophagy pathway
      have also been shown to play important roles in antiviral immunity. In this
      review, we provide an overview of the current understanding of the main insect
      antiviral pathways and examine recent findings that further our understanding of
      the roles of these pathways in facilitating a systemic and specific response to
      infecting viruses. 

PMID- 24120683
TI  - Mechanisms of MAVS regulation at the mitochondrial membrane.
AB  - Mitochondria have emerged as critical platforms for antiviral innate immune
      signaling. This is due in large part to the mitochondrial localization of the
      innate immune signaling adaptor MAVS (mitochondrial antiviral signaling protein),
      which coordinates signals received from two independent cytosolic pathogen
      recognition receptors (PRRs) to induce antiviral genes. The existence of a shared
      adaptor for two central PRRs presents an ideal target by which the host cell can
      prevent cellular damage induced by uncontrolled inflammation through alteration
      of MAVS expression and/or signaling. In this review, we focus on the MAVS
      regulome and review the cellular factors that regulate MAVS by (1) protein
      protein interactions, (2) alterations in mitochondrial dynamics, and/or (3) post
      translational modifications. 

PMID- 24120684
TI  - Ochratoxin A induces karyomegaly and cell cycle aberrations in renal tubular
      cells without relation to induction of oxidative stress responses in rats.
AB  - Ochratoxin A (OTA) is a renal carcinogen that induces karyomegaly in target renal
      tubular cells of the outer stripe of the outer medulla (OSOM). This study was
      performed to clarify the relationship between oxidative stress and the
      karyomegaly-inducing potential involving cell cycle aberration of OTA in the
      OSOM. Rats were treated with OTA for 28 days in combination with enzymatically
      modified isoquercitrin (EMIQ) or alpha-lipoic acid (ALA) as antioxidants. OTA
      increased the mRNA levels of the antioxidant enzyme-related genes Gpx1, Gpx2,
      Gstm1 and Nfe2l2, but did not increase the levels of Gsta5, Keap1, Nqo1, Hmox1,
      Aldh1a1, Por, Prdx1 and Txn1. OTA also did not change the levels of
      thiobarbituric acid-reactive substances, glutathione disulfide/reduced
      glutathione, and the immunoreactive tubular cell distribution of nuclear factor
      erythroid 2-related factor 2 in the OSOM. Co-treatment with EMIQ or ALA did not
      cause any changes in these parameters. As previously reported, OTA increased cell
      proliferation activity, apoptosis and immunohistochemical cellular distributions
      of molecules suggestive of induction of DNA damage and cell cycle aberrations
      involving spindle checkpoint disruption and cell cycle arrest. However, co
      treatment with EMIQ or ALA did not suppress these changes, and ALA co-treatment
      increased the cell proliferation activity induced by OTA. These results suggest
      that OTA facilitates cell cycling involving cell cycle aberrations and apoptosis
      as a basis of the mechanism behind the development of karyomegaly and subsequent
      carcinogenicity targeting the OSOM, without relation to induction of oxidative
      stress. On the other hand, ALA may promote the OTA-induced proliferation of
      carcinogenic target cells. 

PMID- 24120686
TI  - Context-dependent differences in grooming behavior among the NIH heterogeneous
      stock and the Roman high- and low-avoidance rats.
AB  - Grooming occurs during/after stress and seems to accompany dearousal. Here,
      grooming was investigated under testing situations involving different levels of
      aversiveness, taking advantage of differences among three rat strains in
      fearfulness/anxiety. Inbred Roman High Avoidance (RHA-I) rats are less
      anxious/fearful than inbred Roman Low Avoidance (RLA-I). The outbred genetically
      heterogeneous stock of rats (NIH-HS), which resembles the RLA-I in many
      behavioral traits, was also studied. Adult male rats (RLA-I: n=9, RHA-I: n=10,
      NIH-HS: n=12) were observed for 30min in: a novel open-field, a novel hole-board
      and in the home-cage. They were also observed during two-way active avoidance
      training. Differences in grooming depended on test situation: (a) No differences
      were found in the home-cage. (b) While tested in a novel environment, RHA-I
      showed less grooming activity than the other rats. (c) After avoidance responses
      appeared, differences among the strains were opposite to the observed in novelty
      tests. Furthermore, results suggest that (i) grooming is mostly suppressed when
      assured aversive experience is under way; (ii) rostral grooming prevails when
      experience with aversive stimuli is unpredictable (novelty) or potential
      (avoidance training); (iii) body grooming increases for a period in novel
      environments. In general, our results support that grooming takes place during
      dearousal. 

PMID- 24120685
TI  - Olfactory cells via nasal biopsy reflect the developing brain in gene expression
      profiles: utility and limitation of the surrogate tissues in research for brain
      disorders.
AB  - Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a
      good surrogate system to address brain disease-associated molecular changes.
      Nonetheless, whether use of this experimental strategy is justified remains
      unclear. Here we compared expression profiles of olfactory cells systematically
      with those from the brain tissues and other cells. Principal component analysis
      indicated that the expression profiles of olfactory cells are very different from
      those of blood cells, but are closer to those of stem cells, in particular
      mesenchymal stem cells, that can be differentiated into the cells of the central
      nervous system. 

PMID- 24120687
TI  - Released selective pressure on a structural domain gives new insights on the
      functional relaxation of mitochondrial aspartyl-tRNA synthetase.
AB  - Mammalian mitochondrial aminoacyl-tRNA synthetases are nuclear-encoded enzymes
      that are essential for mitochondrial protein synthesis. Due to an endosymbiotic
      origin of the mitochondria, many of them share structural domains with homologous
      bacterial enzymes of same specificity. This is also the case for human
      mitochondrial aspartyl-tRNA synthetase (AspRS) that shares the so-called
      bacterial insertion domain with bacterial homologs. The function of this domain
      in the mitochondrial proteins is unclear. Here, we show by bioinformatic analyses
      that the sequences coding for the bacterial insertion domain are less conserved
      in opisthokont and protist than in bacteria and viridiplantae. The divergence
      suggests a loss of evolutionary pressure on this domain for non-plant
      mitochondrial AspRSs. This discovery is further connected with the herein
      described occurrence of alternatively spliced transcripts of the mRNAs coding for
      some mammalian mitochondrial AspRSs. Interestingly, the spliced transcripts
      alternately lack one of the four exons that code for the bacterial insertion
      domain. Although we showed that the human alternative transcript is present in
      all tested tissues; co-exists with the full-length form, possesses 5'- and 3'
      UTRs, a poly-A tail and is bound to polysomes, we were unable to detect the
      corresponding protein. The relaxed selective pressure combined with the
      occurrence of alternative splicing, involving a single structural sub-domain,
      favors the hypothesis of the loss of function of this domain for AspRSs of
      mitochondrial location. This evolutionary divergence is in line with other
      characteristics, established for the human mt-AspRS, that indicate a functional
      relaxation of non-viridiplantae mt-AspRSs when compared to bacterial and plant
      ones, despite their common ancestry. 

PMID- 24120688
TI  - Myelin peroxisomes - essential organelles for the maintenance of white matter in
      the nervous system.
AB  - Peroxisomes are cellular compartments primarily associated with lipid metabolism.
      Most cell types, including nervous system cells, harbor several hundred of these
      organelles. The importance of peroxisomes for central nervous system white matter
      is evidenced by a variety of human peroxisomal disorders with neurological
      impairment frequently involving the white matter. Moreover, the most frequent
      childhood white matter disease, X-linked adrenoleukodystrophy, is a peroxisomal
      disorder. During the past decade advances in imaging techniques have enabled the
      identification of peroxisomes within the myelin sheath, especially close to nodes
      of Ranvier. Although the function of myelin peroxisomes is not solved yet on
      molecular level, recently acquired knowledge suggests a central role for these
      organelles in axo-glial metabolism. This review focuses on the biology of myelin
      peroxisomes as well as on the pathology of myelin and myelinated axons that is
      observed as a consequence of partial or complete peroxisomal dysfunction in the
      brain. 

PMID- 24120689
TI  - Prolactin and adipose tissue.
AB  - The pituitary lactogenic hormone prolactin (PRL) exerts various physiological
      actions in humans and rodents via its binding to a membrane receptor. Beside its
      role in lactation and reproduction, accumulating evidence suggests that PRL has a
      crucial impact on energy balance by acting on two key players, the pancreas and
      the adipose tissue. Adipose tissue is now recognized as an endocrine organ and
      its metabolic activity appears to play an important role in pathophysiology such
      as obesity and diabetes. White adipocytes store excess of energy in the form of
      triglycerides for future need while brown adipocytes metabolize lipids and
      glucose to produce heat, highlighting their different metabolic functionality.
      The plasticity of white adipose tissue, by the emergence of beige adipocytes,
      appears to be essential in energy homeostasis. PRL receptor deficient mice
      provided direct evidence that PRL signaling is involved in the regulation of
      adipogenesis affecting energy balance and metabolic adaptation most notably
      during development. Moreover, it was demonstrated that PRL signaling participates
      to brown adipose tissue differentiation and function, opening novel understanding
      of hormonal regulation of energy balance. This review summarizes our current
      knowledge about PRL signaling and its role on adipose tissue. 

PMID- 24120690
TI  - Plasma apolipoprotein H levels are different between aspirin induced respiratory
      diseases and aspirin tolerant asthma.
AB  - Aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of
      attention because of its association with increased asthma severity. To identify
      plasma biomarkers for the prediction of AERD, the six most abundant plasma
      proteins (albumin, IgG, antitrypsin, IgA, transferrin, and haptoglobin) in pooled
      plasma samples were removed using a multiple affinity removal system column. Two
      dimensional gel electrophoresis (2DE) was used for differential display proteomic
      analysis of the pooled plasma. Proteins were identified by matrix assisted laser
      desorption ionization time-of-flight (MALDI-TOF)/TOF. Enzyme-linked immunosorbent
      assay (ELISA) was performed to identify and quantify apolipoprotein H (Apo H) in
      plasma from subjects with AERD and aspirin-tolerant asthma (ATA). Eight protein
      spots showed differences in relative intensity between pooled plasma from
      subjects with AERD (n = 8) and those with ATA (n = 8). MALDI-TOF/TOF analysis
      showed decreases in the levels of alpha-fibrinogen precursor, Apo H, fibrin beta,
      and proapolipoprotein in AERD as compared with ATA, and increases in chain A
      human complement component C3, 90-kDa heat shock protein, complement component
      C4a, and kininogen-1 isoform 2. Apo H concentrations were significantly increased
      in plasma from subjects with ATA than those with AERD and normal controls, as
      measured by ELISA (P < 0.01). AERD is characterized by changes in the levels of
      proteins involved in the coagulation and complement pathways. In addition, Apo H
      is up-regulated in ATA compared to AERD and normal controls, suggesting that Apo
      H may be involved in different pathogenesis of ATA from AERD. 

PMID- 24120691
TI  - Structural analysis and cross-protective efficacy of recombinant 87 kDa outer
      membrane protein (Omp87) of Pasteurella multocida serogroup B:2.
AB  - Pasteurella multocida serogroup B:2, a causative agent of haemorrhagic
      septicaemia (HS) in cattle and buffalo especially in tropical regions of Asian
      and African countries, is known to possess several outer membrane proteins (OMPs)
      as immunogenic antigens. In the present study, omp87 gene encoding for 87 kDa OMP
      (Omp87) protein of P. multocida serogroup B:2 strain P52, has been amplified
      (~2304 bp), cloned in to pET32a vector and over-expressed in recombinant
      Escherichia coli as fusion protein. The recombinant Omp87 protein (~102 kDa)
      including N-terminus hexa-histidine tag was purified under denaturing condition.
      Immunization of mice with rOmp87 resulted in increased antigen specific IgG
      titres in serum and provided protection of 66.6 and 83.3% following homologous
      (B:2) and heterologous (A:1) challenge, respectively. A homology model of Omp87
      revealed the presence of two distinct domains; N-terminal domain with four POTRA
      repeats in the periplasmic space and a pore forming C-terminal beta-barrel domain
      (beta1- beta16) in the outer membrane of P. multocida, which belong to Omp85-TpsB
      transporter superfamily of OMPs. The study indicated the potential possibilities
      to use rOmp87 protein along with suitable adjuvant in developing subunit vaccine
      for haemorrhagic septicaemia and pasteurellosis in livestock. 

PMID- 24120692
TI  - Neurologic toxicity of lidocaine during awake intubation in a patient with tongue
      base abscess. Case report.
AB  - Lidocaine is commonly used for topical anesthesia of the upper airway in patient
      with anticipated difficult tracheal intubation undergoing awake fiberoptic
      intubation. Lidocaine toxicity is dose related and proportional to its plasma
      level. Although neurologic toxicity has been frequently observed with intravenous
      use, it has also been reported for topical use. We report on a case of a patient
      with base tongue abscess who developed sudden seizures and coma during
      application of topical anesthesia with lidocaine for awake fiberoptic intubation.
      The presence of a deep neck infection that causes hyperemia and edema of the
      pharyngolaryngeal mucosa may enhance transmucosal systemic absorption of local
      anesthetic. Moreover, conditions such as hypercarbia, dysphagia, or hepatic
      diseases are known to facilitate onset of lidocaine neurologic toxicity with
      serum concentration lower than normal. These findings should be kept in mind
      before administering topical anesthesia of the upper airway. In the presence of
      any of these conditions above, either the total dose of local anesthetic or its
      concentration should be reduced as much as possible. 

PMID- 24120693
TI  - Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and
      in CD34+ stem cell-engrafted NOD/SCID/IL-2Rgammac null mice.
AB  - Current strategies in cellular immunotherapy of cancer and viral infections
      include the adoptive transfer of T cell receptor (TCR) and chimeric antigen
      receptor engineered T cells. When using transient RNA expression systems in
      clinical studies, multiple infusions with receptor-redirected T cells appear
      necessary. However, in allogeneic hematopoietic stem-cell transplantation,
      repeated transfer of donor-derived T cells increases the risk of alloreactive
      graft-versus-host disease. We investigated naive-derived (TN), memory-derived
      (TM), and Epstein Barr virus-specific (TEBV) CD8(+) T cell subsets for
      alloreactivity upon redirection with RNA encoding a cytomegalovirus-specific
      model TCR. We observed that alloreactivity to human leukocyte antigen (HLA)
      mismatched hematopoietic cells developed at much stronger levels in TN compared
      with TM or TEBV populations in cytokine-release and cytotoxicity assays.
      Cytomegalovirus-specific effector function was higher in TCR-transfected TEBV and
      TM over TN cells. To measure alloreactivity in vivo, we reconstituted NOD/SCID/IL
      2Rgammac(null) mice with human CD34(+) stem cells and adoptively transferred them
      with CD8(+) T cell subsets previously stimulated against cells of the HLA
      mismatched stem-cell donor. TN cells showed a significant ability to eliminate
      CD34-derived hematopoietic cells, which was not found with TM and TEBV cells.
      This reduced alloreactive potential along with strong effector function upon
      receptor RNA engineering makes CD8(+) memory and EBV-specific T cells
      advantageous tools in adoptive immunotherapy after allogeneic transplantation.

PMID- 24120694
TI  - Genetic diversity and features analysis of type VI secretion systems loci in
      avian pathogenic Escherichia coli by wide genomic scanning.
AB  - Avian pathogenic Escherichia coli (APEC) strains frequently cause extra
      intestinal infections and significant economic losses. Recent studies revealed
      that the type VI secretion system (T6SS) is involved in APEC pathogenesis. Here
      we provide the first evidence of three distinguishable and conserved T6SS loci in
      APEC genomes. In addition, we present the prevalence and comparative genomic
      analysis of these three T6SS loci in 472 APEC isolates. The prevalence of T6SS1,
      T6SS2 and T6SS3 loci were 14.62% (69/472), 2.33% (11/472) and 0.85% (4/472)
      positive in the APEC collections, respectively, and revealed that >85% of the
      strains contained T6SS loci which consisted of the virulent phylogenetic groups D
      and B2. Comprehensive analysis showed prominent characteristics of T6SS1 locus,
      including wildly prevalence, rich sequence diversity, versatile VgrG islands and
      excellent expression competence in various E. coli pathotypes. Whereas the T6SS2
      locus infatuated with ECOR groups B2 and sequence conservation, of which are only
      expressed in meningitis E. coli. Regrettably, the T6SS3 locus was encoded in
      negligible APEC isolates and lacked several key genes. An in-depth analysis about
      VgrG proteins indicated that their COG4253 and gp27 domain were involved in the
      transport of putative effector islands and recognition of host cells
      respectively, which revealed that VgrG proteins played an important role in
      functions formation of T6SS. 

PMID- 24120695
TI  - Characteristics of the variance effective population size over time using an age
      structured model with variable size.
AB  - The variance effective population size (NeV) is a key concept in population
      biology, because it quantifies the microevolutionary process of random genetic
      drift, and understanding the characteristics of NeV is thus of central
      importance. Current formulas for NeV for populations with overlapping generations
      weight age classes according to their reproductive values (i.e. reflecting the
      contribution of genes from separate age classes to the population growth) to
      obtain a correct measure of genetic drift when computing the variance of the
      allele frequency change over time. In this paper, we examine the effect of
      applying different weights to the age classes using a novel analytical approach
      for exploring NeV. We consider a haploid organism with overlapping generations
      and populations of increasing, declining, or constant expected size and
      stochastic variation with respect to the number of individuals in the separate
      age classes. We define NeV, as a function of how the age classes are weighted,
      and of the span between the two points in time, when measuring allele frequency
      change. With this model, time profiles for NeV can be calculated for populations
      with various life histories and with fluctuations in life history composition,
      using different weighting schemes. We examine analytically and by simulations
      when NeV, using a weighting scheme with respect to reproductive contribution of
      separate age classes, accurately reflect the variance of the allele frequency
      change due to genetic drift over time. We show that the discrepancy of NeV,
      calculated with reproductive values as weights, compared to when individuals are
      weighted equally, tends to a constant when the time span between the two
      measurements increases. This constant is zero only for a population with a
      constant expected population size. Our results confirm that the effect of
      ignoring overlapping generations, when empirically assessing NeV from allele
      frequency shifts, gets smaller as the time interval between samples increases.
      Our model has empirical applications including assessment of (i) time intervals
      necessary to permit ignoring the effect of overlapping generations for NeV
      estimation by means of the temporal method, and (ii) effects of life table
      manipulation on NeV over varying time periods.

PMID- 24120696
TI  - Every patient with atrial fibrillation has his (her) own optimal heart rate.
AB  - Heart rate control is an important part of atrial fibrillation (AF) treatment and
      the recommendation for the target rate has become lenient in the recent
      guideline. Since heart rhythm of AF patients is irregularly irregular with great
      rate variation, the number of effective ventricular contractions may be different
      within a given time period among patients with similar heart rates and it may
      further lead to different levels of cardiac output. Therefore, we propose that
      every AF patient has his (her) own optimal heart rate, or to say that, the target
      for rate control in each AF patient should be individualized. This optimal heart
      rate can be defined by pulse counting, echocardiography or cardiopulmonary
      exercise test. With this new target, patients will achieve higher cardiac output
      with better exercise tolerance and life quality, even an improved prognosis. 

PMID- 24120697
TI  - Disturbed sleep in bipolar disorder is related to an elevation of IL-6 in
      peripheral monocytes.
AB  - Bipolar disorder is a severe psychiatric disorder that is associated with
      persistent changes in the quality, duration and architecture of sleep. Currently
      there is no unifying hypothesis explaining the alterations in sleep observable in
      patients with bipolar disorder and management is often difficult though vital.
      Sleep is modified by various cytokines including IL-6. Elevated levels of IL-6
      are associated with a poorer quality of sleep and changes in the architecture of
      sleep similar to those observed in bipolar disorder. Therapeutic administration
      of Interferon causes elevations of intrathecal IL-6 concentrations and appears to
      provoke a deteriorating quality of sleep. The blockade of IL-6 with tocilizumab
      in rheumatoid arthritis is associated with improvements in the quality of sleep.
      Bipolar disorder is associated with elevated levels of IL-6 and in particular
      elevated levels of mRNA coding for IL-6 in peripheral monocytes. We propose that
      the changes observed in the sleep of patients with bipolar disorder are related
      to the elevation of IL-6 and that this correlates with an elevated expression of
      mRNA coding for IL-6 expression in peripheral monocytes. 

PMID- 24120699
TI  - PIAS3 may represent a potential biomarker for diagnosis and therapeutic of human
      colorectal cancer.
AB  - Colorectal cancer (CRC) is a challenging problem both for the developed and
      underdeveloped countries. Despite numerous improvements in early diagnosis and
      treatment, the incidence and mortality is still keeping in a high level. Molecule
      targeted therapy has drawn much attention as next generation anticancer agents
      for diagnosis and therapeutic of CRC. Protein Inhibitor of Activated Signal
      Transducer and Activators of Transcription 3 (PIAS3) as a novel biomarker has
      been focused to have a role in the development of malignancy, which was expressed
      at a higher level in most common malignancies compared with corresponding normal
      tissues. Furthermore, evidences suggest that the expression of PIAS3 can affect
      the growth of cancer cells by inhibiting the JAK/STAT and PI3-K/Akt signaling
      pathways or regulating its SUMO (small-ubiquitin like modifiers) ligase activity
      in some malignancy. Therefore, we hypothesized that PIAS3 may be a potential
      biomarker target for early cancer detection and therapeutic of human CRC. 

PMID- 24120698
TI  - Gestational vitamin A deficiency: a novel cause of sensorineural hearing loss in
      the developing world?
AB  - Hearing loss is a substantial public health problem with profound social and
      economic consequences in the developing world. The World Health Organization
      (WHO) estimates that there are 360 million people living with disabling hearing
      loss globally, and 80% of these individuals are from low- and middle-income
      countries. The epidemiology of hearing impairment remains poorly defined in most
      impoverished societies. Middle ear infections in childhood are a key determinant;
      however, congenital anomalies may also comprise an important etiology and may
      arise from gestational malnutrition. While evidence exists that preventable
      vitamin A deficiency exacerbates the severity of ear infections and,
      consequently, hearing loss, antenatal vitamin A deficiency during sensitive
      periods of fetal development may represent an etiologically distinct and
      virtually unexplored causal pathway. Evidence from multiple animal systems
      clearly shows that fetal inner ear development requires adequate vitamin A
      nutriture to proceed normally. Inner ear malformations occur in experimentally
      imposed maternal vitamin A deficiency in multiple species in a dose-response
      manner. These anomalies are likely due to the loss of retinoic acid-dependent
      regulation of both hindbrain development and otic morphogenic processes. Based on
      in vivo evidence in experimental animals, we hypothesize that preventable
      gestational vitamin A deficiency, especially during early stages of fetal
      development, may predispose offspring to inner ear malformations and
      sensorineural hearing loss. As vitamin A deficiency affects an estimated 20
      million pregnant women globally, we hypothesize that, in undernourished settings,
      routine provision of supplemental vitamin A at the recommended allowance
      throughout pregnancy may promote normal inner ear development and reduce risk of
      an as yet unknown fraction of sensorineural hearing loss. If our hypothesis
      proves correct, gestational vitamin A deficiency would represent a potentially
      preventable etiology of sensorineural hearing loss of substantial public health
      significance.

PMID- 24120700
TI  - Myelin and traumatic brain injury: the copper deficiency hypothesis.
AB  - Nearly two million people suffer traumatic brain injury in the US each year.
      These injuries alter adversely the metabolism of myelin, a major lipid material
      in brain, both in people and in experimental injuries of animals. A newly
      discovered and severe human neuropathy from copper deficiency provides evidence
      that some people in the US are malnourished in copper. As it is well known among
      copper cognoscenti that it is impossible to synthesize myelin if copper nutriture
      is inadequate, it seems reasonable to assume that repair will be poor in this
      situation. Copper status of patients should be evaluated and experiments with
      injured animals should be repeated with graded doses of copper to determine if
      copper metabolism is important in this illness. 

PMID- 24120701
TI  - RE: Introducing the HOPE (Hypospadias Objective Penile Evaluation)-score: a
      validation study of an objective scoring system for evaluating cosmetic
      appearance in hypospadias patients.

PMID- 24120702
TI  - Characterization of translocations in mesenchymal hamartoma and undifferentiated
      embryonal sarcoma of the liver.
AB  - BACKGROUND: Mesenchymal hamartoma of the liver (MHL) is an uncommon benign
      primary liver tumor that typically occurs in the pediatric population, although
      cases have been described in adults. MHL is sometimes associated with the highly
      malignant undifferentiated embryonal sarcoma (UES), and the synchronous or
      metachronous occurrence of MHL and UES suggests they share a common genetic link.
      Although the exact mechanism of tumorigenesis has not been identified, MHL cases
      harbor recurring chromosomal rearrangements involving 19q13. DESIGN: In order to
      provide more details on the genetic events of MHL tumorigenesis, capture-based
      next generation sequencing (NGS) targeted to loci recently shown to be involved
      in a translocation in a case of UES arising in MHL (specifically, the MALAT1 gene
      on chromosome 11 and a gene poor region termed MHLB1 on chromosome 19) was
      performed on formalin fixed paraffin embedded tissue from seven cases of MHL.
      RESULTS: Chromosome rearrangements involving the MHLB1 locus were identified in
      three of the seven cases, including the translocation t(11,19)(q13.1;q13.42)
      involving the MALAT1 gene; the translocation t(2,19)(q31.1;q13.42) involving
      AK023515, an uncharacterized noncoding gene; and the inversion
      inv(19,19)(q13.42;q13.43) involving the PEG3 gene encoding a Kruppel-type zinc
      finger protein. Rearrangements were exclusively identified in pediatric tumors.
      In each case, the presence of the rearrangement was confirmed by PCR and
      interphase FISH. Interphase FISH also demonstrated that the arrangements occur
      within the spindle cell component but not within the epithelial components of the
      tumor. CONCLUSIONS: Since the MHLB1 locus contains a CpG-rich region whose
      methylation regulates C19MC miRNA genes, rearrangements that disrupt this region
      may contribute to MHL development through alteration of miRNA expression. The
      demonstration that the loose stromal cells harbor the rearrangements indicates
      that (some cases of) MHL are a neoplastic process due to a somatic genetic change
      and not a germline abnormality.

PMID- 24120704
TI  - Plasma visfatin, a possible prognostic marker in aneurysmal subarachnoid
      hemorrhage.
AB  - Visfatin is linked to inflammation and associated with clinical outcomes of
      intracerebral hemorrhage. This study was designed to investigate whether visfatin
      might serve as a marker of severity and prognosis in aneurysmal subarachnoid
      hemorrhage. In this study, plasma visfatin levels of 172 consecutive patients and
      172 sex and age-matched healthy subjects were determined using enzyme-linked
      immunosorbent assay. The recorded clinical outcomes included in-hospital
      mortality and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale
      score of 1-3). Plasma visfatin level was substantially higher in patients than in
      healthy controls (92.1 +/- 20.5 ng/mL vs. 12.4 +/- 3.2 ng/mL; P<0.001), was
      significantly associated with the World Federation of Neurological Surgeons
      (WFNS) score (r=0.569, P<0.001) and Fisher score (r=0.657, P<0.001), was an
      independent predictor of in-hospital mortality [odds ratio (OR), 1.378; 95%
      confidence interval (CI), 1.036-1.866; P=0.002] and 6-month mortality (OR, 1.261;
      95% CI, 1.018-1.745; P=0.004) and unfavorable outcome (OR, 1.207; 95% CI, 1.012
      1.682; P=0.008) in multivariate logistic regression analysis and had high
      predictive value for in-hospital mortality [area under curve (AUC), 0.849; 95%
      CI, 0.787-0.899; P<0.001] and 6-month mortality (AUC, 0.868; 95% CI, 0.808-0.915;
      P<0.001) and unfavorable outcome (AUC, 0.859; 95% CI, 0.797-0.907; P<0.001) using
      receiver operating characteristic curves. AUCs of visfatin were similar to those
      of WFNS score and Fisher score (all P>0.05), but visfatin did not improve the
      predictive values of WFNS score and Fisher score (all P>0.05). Thus, visfatin may
      be associated with clinical severity of aneurysmal subarachnoid hemorrhage and
      also have prognostic value for clinical outcomes.

PMID- 24120703
TI  - The roles of C-terminal helices of human apolipoprotein A-I in formation of high
      density lipoprotein particles.
AB  - Apolipoprotein A-I (apoA-I) accepts cholesterol and phospholipids from ATP
      binding cassette transporter A1 (ABCA1)-expressing cells to form high-density
      lipoprotein (HDL). Human apoA-I has two tertiary structural domains and the C
      terminal domain (approximately amino acids 190-243) plays a key role in lipid
      binding. Although the high lipid affinity region of the C-terminal domain of apoA
      I (residues 223-243) is essential for the HDL formation, the function of low
      lipid affinity region (residues 191-220) remains unclear. To evaluate the role of
      residues 191-220, we analyzed the structure, lipid binding properties, and HDL
      formation activity of Delta191-220 apoA-I, in comparison to wild-type and
      Delta223-243 apoA-I. Although deletion of residues 191-220 has a slight effect on
      the tertiary structure of apoA-I, the Delta191-220 variant showed intermediate
      behavior between wild-type and Delta223-243 regarding the formation of
      hydrophobic sites and lipid interaction through the C-terminal domain.
      Physicochemical analysis demonstrated that defective lipid binding of Delta191
      220 apoA-I is due to the decreased ability to form alpha-helix structure which
      provides the energetic source for lipid binding. In addition, the ability to form
      HDL particles in vitro and induce cholesterol efflux from ABCA1-expressing cells
      of Delta191-220 apoA-I was also intermediate between wild-type and Delta223-243
      apoA-I. These results suggest that despite possessing low lipid affinity,
      residues 191-220 play a role in enhancing the ability of apoA-I to bind to and
      solubilize lipids by forming alpha-helix upon lipid interaction. Our results
      demonstrate that the combination of low lipid affinity region and high lipid
      affinity region of apoA-I is required for efficient ABCA1-dependent HDL
      formation. 

PMID- 24120705
TI  - Purification, structural elucidation and bioactivity of tryptophan containing
      diketopiperazines, from Comamonas testosteroni associated with a rhabditid
      entomopathogenic nematode against major human-pathogenic bacteria.
AB  - The cell free culture filtrate of a Comamonas testosteroni associated with an
      Entomopathogenic nematode (EPN), Rhabditis (Oscheius) sp. exhibited promising
      antimicrobial activity. The ethyl acetate extract of the bacterial culture
      filtrate was purified by silica gel column chromatography to obtain five
      diketopiperazines or cyclic dipeptides (DKP 1-5). The structure and absolute
      stereochemistry of the compounds were determined based on extensive spectroscopic
      analyses (HR-MS, (1)HNMR, (13)CNMR, (1)H-(1)H COSY, (1)H-(13)C HMBC) and Marfey's
      method. Based on the spectral data the compounds were identified as Cyclo-(L-Trp
      L-Pro) (1), Cyclo-(L-Trp-L-Tyr) (2), Cyclo-(L-Trp-L-Ile) (3), Cyclo-(L-Trp-L-Leu)
      (4) and Cyclo-(L-Trp-L-Phe) (5), respectively. Three diketopiperazines (DKP 2, 3
      and 5) were active against all the ten bacteria tested. The highest activity of
      0.5MUg/ml by Cyclo-(L-Trp-L-Phe) was recorded against Vibrio cholerae followed by
      Salmonella typhi (1 MUg/ml) a human pathogen responsible for life threatening
      diseases like profuse watery diarrhea and typhoid or enteric fever. The activity
      of this compound against V. cholerae and S. typhi is more effective than
      ciprofloxacin and ampicillin, the standard antibiotics. Cyclo-(L-Trp-L-Phe)
      recorded significant antibacterial activity against all the test bacteria when
      compared to other compounds. Five diketopiperazines were active against all the
      test fungi and are more effective than bavistin the standard fungicide.
      Diketopiperazines recorded no cytotoxicity to FS normal fibroblast and VERO cells
      (African green monkey kidney) except DKP 3 and 4. To our best knowledge this is
      the first report of antimicrobial activity of the tryptophan containing
      diketopiperazines against the human pathogenic microbes. The production of cyclic
      dipeptides by C. testosteroni is also reported here for the first time. We
      conclude that the C. testosteroni is promising sources of natural bioactive
      secondary metabolites against human pathogenic bacteria which may receive great
      benefit in the field of human medicine in near future.

PMID- 24120706
TI  - Evidence of ancillary trigeminal innervation of levator palpebrae in the general
      population.
AB  - The cranial synkineses are a group of disorders encompassing a variety of
      involuntary co-contractions of the facial, masticatory, or extraocular muscles
      that occur during a particular volitional movement. The neuroanatomical pathways
      for synkineses largely remain undefined. Our studies explored a normal synkinesis
      long observed in the general population - that of jaw opening during efforts to
      open the eyelids widely. To document this phenomenon, we observed 186 consecutive
      participants inserting or removing contact lenses to identify jaw opening.
      Seeking electrophysiological evidence, in a second study we enrolled individuals
      undergoing vascular decompression for trigeminal neuralgia or hemifacial spasm,
      without a history of jaw-winking, ptosis, or strabismus, to record any motor
      responses in levator palpebrae superioris (LPS) upon stimulation of the
      trigeminal motor root. Stimulus was applied to the trigeminal motor root while an
      electrode in levator recorded the response. We found that 37 participants (20%)
      opened their mouth partially or fully during contact lens manipulation. In the
      second study, contraction of LPS with trigeminal motor stimulation was documented
      in two of six patients, both undergoing surgery for trigeminal neuralgia. We
      speculate these results might provide evidence of an endogenous synkinesis,
      indicating that trigeminal-derived innervation of levator could exist in a
      significant minority of the general population. Our observations demonstrate
      plasticity in the human cranial nerve innervation pattern and may have
      implications for treating Marcus Gunn jaw-winking. 

PMID- 24120707
TI  - Hypoglycaemia risk among a hospitalised stroke patient cohort: a case for
      increased vigilance in glucose monitoring.
AB  - We conducted a retrospective cohort study involving a review of the records of
      112 patients consecutively admitted with acute stroke or transient ischaemic
      attack (TIA) to all three district general hospitals in one Health and Social
      Care Trust in Northern Ireland from 1 January to 15 April 2008. Glucose results
      for each of the first 5 days of hospital admission were ascertained. We compared
      interventions and clinical outcome between patients who experienced hypoglycaemia
      (glucose<4.0 mmol/l) in the first 5 days, and patients with higher glucose
      results. Our results indicated that 11 (10%) patients experienced incidents of
      hypoglycaemia ranging from 1.8 to 3.9 mmol/l. None of the individuals affected
      had received intravenous or subcutaneous insulin. Only two of the hypoglycaemic
      episodes involved patients with a history of diabetes mellitus. Two patients
      experienced episodes of hypoglycaemia on 2 or more days. Six patients experienced
      hypoglycaemia at the lower threshold of glucose<3.5 mmol/l and this was not
      associated with a history of diabetes. A history of diabetes mellitus prompted
      near patient glucose testing, but among patients without diagnosed diabetes,
      glycaemia was under-monitored. The test that most frequently indicated
      hypoglycaemia was a routine electrolyte profile tested in the hospital
      laboratory. Patients in the first 5 days after stroke have a small risk of
      hypoglycaemia. There is a need for greater vigilance in the monitoring of glucose
      among patients admitted to hospital with stroke or TIA.

PMID- 24120708
TI  - The role of vascular remodeling and inflammation in the pathogenesis of
      intracranial aneurysms.
AB  - While the mechanisms triggering pathogenesis of intracranial aneurysms have not
      been fully elucidated, different mechanisms have been proposed ranging from
      hemodynamic mechanisms to genetic predispositions. One mechanism that has been
      thoroughly explored is the physiological and pathological vascular remodeling
      that occurs in conjunction with inflammatory reactions resulting in the
      initiation and progression of these lesions. Both hemodynamic stimuli and
      vascular inflammation can trigger a series of biochemical reactions resulting in
      vascular smooth muscle cell apoptosis and migration causing thinned, dilated
      areas of the cerebral vasculature. In addition, an imbalance between
      extracellular matrix remodeling proteins, such as matrix metalloproteinases and
      their inhibitors, can result in accelerated degradation of the internal elastic
      lamina and the adventitial layers, further weakening the vessel. While these
      processes occur under normal physiological conditions, situations that alter
      their balance such as inflammation caused by cigarette smoking or cocaine usage
      or hypoxia induced under chronic hypertensive conditions can alter the delicate
      balance of these reactions potentiating pathological remodeling and aneurysm
      development. The present study represents a thorough literature review of the
      vascular remodeling and inflammatory components to aneurysmal pathogenesis. 

PMID- 24120709
TI  - Popliteus muscle hemorrhage as a rare cause of a proximal tibial neuropathy.
AB  - Proximal tibial neuropathy is an uncommon focal mononeuropathy that is most often
      caused by trauma, ischemia, or neoplastic infiltration or compression of the
      tibial nerve. We report a patient who presented with a tibial neuropathy
      following a leg injury, which initially mimicked a lumbosacral radiculopathy but
      which was the result of a proximal tibial neuropathy. Electrophysiologic studies
      confirmed a proximal tibial neuropathy and MRI revealed a popliteus muscle
      hemorrhage with mass effect on the tibial nerve. Following conservative
      management the patient had little recovery of function after 15 months.

PMID- 24120710
TI  - New generation intraoperative three-dimensional imaging (O-arm) in 100 spine
      surgeries: does it change the surgical procedure?
AB  - The O-arm (Medtronic Sofamor Danek, Inc., Memphis, TN, USA), an intraoperative CT
      scan imaging system, may provide high-quality imaging information to the surgeon.
      To our knowledge, its impact on spine surgery has not been studied. We reviewed
      100 consecutive spine surgical procedures which utilized the new generation
      mobile intraoperative CT imaging system (O-arm). The most common diagnoses were
      degenerative conditions (disk disease, spondylolisthesis, stenosis and acquired
      kyphosis), seen in 49 patients. The most common indication for imaging was spinal
      instrumentation in 81 patients (74 utilized pedicle screws). In 52 (70%) of
      these, the O-arm was used to assess screw position after placement; in 22 (30%),
      it was coupled with Stealth navigation (Medtronic Sofamor Danek, Inc.) to guide
      screw placement. Another indication was to assess adequacy of spinal
      decompression in 38 patients; in 19 (50%) of these, intrathecal contrast material
      was used to obtain an intraoperative CT myelogram. In 20 patients O-arm findings
      led to direct surgeon intervention in the form of screw removal/repositioning
      (n=13), further decompression (n=6), interbody spacer repositioning (n=1), and
      removal of kyphoplasty trocar (n=1). In 20% of spine surgeries, the procedure was
      changed based on O-arm imaging findings. We found the O-arm to be useful for
      assessment of instrumentation position, adequacy of spinal decompression, and
      confirmation of balloon containment and cement filling in kyphoplasty. When used
      with navigation for image-guided surgery, it obviated the need for registration. 

PMID- 24120711
TI  - Prospective randomized, double-blind, placebo controlled trial to evaluate
      infection prevention in adult patients after tension-free inguinal hernia repair.
AB  - OBJECTIVE: Infection is one of possible complications after prosthetic material
      hernia repair surgery. Antibiotic prophylaxis is applied routinely in China, but
      its effect is still controversial. The present study aims to offer direct
      clinical evidence on prevention of infection after tension-free inguinal hernia
      repair. METHODS: A total of 1,200 cases with primary inguinal hernia treated in 6
      hospitals in Shaanxi Province were enrolled in this study. They were randomly
      divided into three groups (n = 400 per group): placebo control group, Cefazolin
      group and Levofloxacin group after tensionfree inguinal hernia repair using
      polypropylene mesh. Hernia type, age, gender, weight and complications were
      recorded. The surgical-site infection was diagnosed according to APIC, CDC
      criteria (http://www.apic. org). Infections were evaluated every other day in the
      first week, and then at 14 days, 21 days and 30 days following surgery. RESULTS:
      Two cases from the placebo group, 3 from the Cefazolin group and 3 from the
      Levofloxacin group failed to follow-up. Six patients (2 non-following the
      protocol, 2 severe depression, and 2 laparoscopic surgery) from the placebo
      group, 14 (8 nonreceiving trial medication, 5 laparoscopic surgery, and 1 failure
      to tolerance) from the Cefazolin group, and 12 (2 combination of antibiotic
      usage, 5 laparoscopic surgery and 5 failure to tolerance) from the Levofloxacin
      group were excluded. The data of the 1,160 cases were statistically analyzed in
      the incidence rates of surgical-site infection and complications after inguinal
      hernia repair. Surgical-site infection including wound infection, cellulitis or
      mesh-related infection was found in 20 cases (5.1%) of the control group, 15
      (3.92%) of the Cefazolin group and 17 (4.42%) of the Levofloxacin group, and the
      difference among the three groups was not statistically significant (chi2 =
      0.438, p = 0.803). There was also no significant difference in post-surgery
      complications including seroma (p = 0.6366), urinary retention (p = 0.8136), fat
      liquefaction (p = 0.8061), pulmonary infection (p = 0.1911), and urinary tract
      infection (p = 0.8144) among the three groups. CONCLUSIONS: Prophylactic use of
      Cefazolin or Levofloxacin did not significantly decrease the risk of wound
      infection in these patients undergoing inguinal hernia repair. The present
      results do not support the administration of antibiotic prophylaxis for tension
      free inguinal hernia repair. *The authors contributed equally to this work.

PMID- 24120712
TI  - Oseltamivir effectiveness in seasonal influenza patients taking symptomatic
      therapy: retrospective analysis of RCT data.
AB  - AIMS: The effectiveness of oseltamivir to improve seasonal influenza symptoms in
      clinical practice was analyzed using pooled data from patients who were also
      taking analgesics and other over-the-counter (OTC) medications. METHODS: Data
      were pooled from 1,709 patients aged 13 - 64 years with confirmed seasonal
      influenza who enrolled in six randomized, placebo-controlled trials of
      oseltamivir (75 mg b.i.d. for 5 days) and took OTC analgesics (+/- other
      medications). Rates of improvement of seven symptoms, two functional measures
      (sleep quality and ability to undertake usual activities) and fever (body
      temperature) were calculated between Days 1 and 6 of illness. Time to reach
      defined tolerability thresholds was compared using Kaplan-Meier analysis. Two
      subgroup analyses were performed in patients taking cough and cold remedies (n =
      635) and antibiotics (n = 175) in addition to analgesics. RESULTS: Six symptoms
      and both functional measures improved faster with oseltamivir than placebo,
      including nasal congestion (difference in rate, 19.3%), cough (34.1%), sleep
      quality (13.7%) and ability to perform usual activities (12.0%). Results in the
      Analgesics + cough/cold subgroup analysis were similar. In the Analgesics +
      antibiotics subgroup, three symptoms and both functional measures improved faster
      with oseltamivir. In all three analyses, median time to reach tolerability
      thresholds for all measures was faster in oseltamivir patients than placebo
      patients. CONCLUSIONS: Oseltamivir treatment of patients with seasonal influenza
      already receiving OTC medications produced a faster reduction in severity of most
      symptoms and a quicker return to ability to perform normal activities compared
      with patients who took OTC medications and placebo.

PMID- 24120713
TI  - A pharmacokinetic assessment of an alternate titration strategy for fentanyl
      pectin nasal spray.
AB  - OBJECTIVE: Fentanyl pectin nasal spray (FPNS) is approved for management of
      breakthrough pain in cancer. It is available in 100 and 400 MUg strength products
      which allow for doses of 100 - 800 MUg (1 or 2 sprays). Existing titration
      strategies require a transition from the 100 MUg product to the 400 MUg product
      when increasing the dose from 200 to 400 MUg. This study assessed the
      pharmacokinetic (PK) profile of FPNS administered as 4 sprays of 100 MUg as an
      alternate titration strategy. METHODS: In this 3-way, crossover study, healthy
      subjects aged 18 - 65 years were randomized to receive each of 3 dosages of FPNS
      (4 * 100 MUg, 2 * 100 MUg, and 1 * 400 MUg). PK samples were collected over 24
      hours. RESULTS: Of 22 subjects randomized, 20 were included in the PK analysis.
      Administration of both 400 MUg regimens (4 * 100 MUg and 1 * 400 MUg) provided
      greater systemic fentanyl exposure compared with the 200 MUg dose (C(max): 1,748
      and 1,485 pg/ml vs. 1,051 pg/ml; AUC(0-1h): 1,012 and 944 pg*h/ml vs. 665
      pg*h/ml; and tmax: 0.25 hours and 0.50 hours vs. 0.25 hours); fentanyl exposure
      after 4 * 100 MUg and 1 * 400 MUg regimens was similar. Adverse events (AEs) were
      all mild or moderate in intensity; most common AEs were nausea (50%) and headache
      (23%). AE frequency was similar across treatments without reports of nasal
      effects. CONCLUSIONS: Given that systemic fentanyl exposure from FPNS
      administered as 4 * 100 MUg is similar to that from FPNS as 1 * 400 MUg, the 4 *
      100 MUg regimen provides an alternate titration strategy for patients needing
      more than 200 MUg. This alternate strategy will facilitate a patient's ability to
      achieve an optimized FPNS regimen and reduce opioid wastage.

PMID- 24120714
TI  - Comparison of methods for evaluation of the suppressive effects of prednisolone
      on the HPA axis and bone turnover: changes in s-DHEAS are as sensitive as the
      ACTH test.
AB  - OBJECTIVE: Different hypothalamic-pituitary-adrenal (HPA) axis function tests are
      used for diagnosing disease and evaluating suppressive effects of corticosteroid
      treatment. Our objectives were to evaluate sensitivity and precision of different
      HPA axis tests to be able to select one that combines good performance with good
      practicability, suitable for investigation of new corticosteroids in clinical
      trials. METHODS: In this descriptive, double-blind, parallel-group study, 60
      healthy male volunteers were treated with once-daily morning doses of
      prednisolone for 2 weeks. The volunteers were randomized to 1 of 5 treatment
      groups (prednisolone 2.5, 5, 7.5, 10, or 15 mg). We compared the plasma-cortisol
      (p-cortisol) 24-hour average concentration (Cav) with morning (08:00 hours) p
      cortisol, daytime p-cortisol Cav, and 24-hour urinary cortisol excretion.
      Adrenocorticotrophic hormone (ACTH) stimulation tests and the metyrapone test
      were also performed. Furthermore, we analyzed levels of serum
      dehydroepiandrosterone sulfate (s-DHEAS), insulin, and markers of bone turnover.
      RESULTS: Dose-related effects were shown, but the magnitude of effects and
      sensitivities varied greatly between the tests. P-cortisol measurements over the
      course of 24 hours were used as the reference method. Low- and standard-dose ACTH
      tests and morning s-DHEAS levels had similar sensitivity. Urinary cortisol
      excretion and the metyrapone stimulation test had low sensitivity. The effects of
      prednisolone on markers of bone turnover were, in general, less than those on the
      HPA axis. Only osteocalcin, procollagen Type 1 C-peptide and procollagen Type 3 N
      peptide were significantly affected. Treatment with prednisolone was well
      tolerated. CONCLUSION: Changes in s-DHEAS and the low-dose ACTH test combine good
      sensitivity and precision for evaluation of the suppressive effect of exogenous
      corticosteroids on the HPA axis, and they are easy to perform.

PMID- 24120715
TI  - High-quality triplicate electrocardiogram monitoring in a first-in-man study:
      potential for early detection of drug-induced QT prolongation.
AB  - BACKGROUND: QT interval prolongation is associated with an increased risk of
      potentially fatal ventricular tachycardias, including torsade de pointes.
      Regulatory guidance recommends the "thorough QT/QTc" (TQT) study as the gold
      standard for assessing the propensity of novel nonantiarrhythmic drugs to delay
      cardiac repolarization. An opportunity exists, however, to use high-quality
      electrocardiogram (ECG) data from first-in-man trials as an exploratory and
      complementary approach to gain early insight into potential risk of QT
      prolongation. METHODS: We collected high-quality, triplicate, 12-lead ECG data
      during a first-in-man trial of a drug developed for the treatment of Type 2
      diabetes that had shown in vitro hERG inhibition and potential to prolong QT
      intervals in an animal model. RESULTS: QTc prolongation was observed at the
      highest dose, leading to a maximum QTcF prolongation > 19 ms at 6 hours after the
      14th daily dose. QTcF increases from time-matched baseline relative to placebo
      were positively correlated with peak plasma concentrations. CONCLUSIONS:
      Clinically relevant QT interval prolongations can be detected during first-in-man
      studies using high-quality ECG monitoring. Such data may facilitate early
      decision making on whether to terminate the development of a compound and invest
      resources in more promising molecules; and it may enable more efficient TQT study
      design or preclude the need for future TQT studies.

PMID- 24120716
TI  - ACE inhibitors and angiotensin receptor blockers could promote the onset of
      endometrial polyps in hypertensive women.
AB  - OBJECTIVE: To investigate whether anti-hypertensive therapy is a risk factor for
      the onset of endometrial polyps in hypertensive women. METHODS: A sample of 305
      hypertensive patients was analyzed. By applying multivariable logistic regression
      analysis, the odds of developing endometrial polyps relative to the known risk
      factors for endometrial polyps and to the class of anti-hypertensive drugs were
      calculated. RESULTS: The variables reaching significance after multivariable
      logistic regression analysis included the following: hypertension not-in-therapy
      (odds ratio 2.544; 95% confidence intervals 1.249 - 5.182; p = 0.010); ACE
      inhibitor therapy (odds ratio 2.400; 95% confidence intervals 1.248 - 4.614; p =
      0.009); angiotensin receptor blockers (odds ratio 2.091; 95% confidence intervals
      1.044 - 4.187; p = 0.037); and fasting glucose level (odds ratio 1.018; 95%
      confidence intervals 1.007 - 1.030; p = 0.001). CONCLUSIONS: Although the results
      should be interpreted carefully, it appears that ACE inhibitors and, to a lesser
      extent, angiotensin receptor blockers may promote the onset of endometrial polyps
      in hypertensive patients.

PMID- 24120717
TI  - Lower metabolic clearance of tizanidine in Japanese subjects.
AB  - Our aim was to determine whether metabolic clearance, renal clearance, or both
      elimination pathways contribute to ethnic differences in tizanidine clearance,
      which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic
      parameters of tizanidine in 9 healthy male Japanese subjects were compared with
      those of Caucasians in previous studies. Metabolic clearance of tizanidine was
      lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg),
      although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The
      results suggest that ethnic differences in tizanidine clearance are due to
      differences in metabolic clearance. 

PMID- 24120718
TI  - No clinically relevant interaction between sugammadex and aspirin on platelet
      aggregation and coagulation parameters.
AB  - OBJECTIVES: This study evaluated interaction potential between sugammadex and
      aspirin on platelet aggregation. METHODS: This was a randomized, double-blind,
      placebo-controlled, four-period crossover study in 26 healthy adult males.
      Treatments were i.v. placebo, i.v. sugammadex 4 mg/kg, and i.v.
      placebo/sugammadex with oncedaily oral aspirin 75 mg. Primary objective was to
      assess interaction between sugammadex and aspirin on platelet aggregation using
      collagen-induced whole-blood aggregometry. Effects on activated partial
      thromboplastin time (APTT) and cutaneous bleeding time were also evaluated.
      Platelet aggregation and APTT were evaluated by geometric mean ratios, using area
      under-effect curves 3 - 30 minutes after sugammadex/placebo dosing. Bleeding time
      ratio was evaluated at 5 minutes post-dosing. Non-inferiority margins were pre
      specified via literature review. Type I error was controlled using a hierarchical
      strategy. RESULTS: Ratio for platelet aggregation for aspirin with sugammadex vs.
      aspirin alone was 1.01, with lower limit of two-sided 90% CI of 0.91(above non
      inferiority margin of 0.75). Ratio for statistical interaction between sugammadex
      and aspirin on APTT was 1.01, with upper 90% CI of 1.04 (below non-inferiority
      margin of 1.50), and for sugammadex vs. placebo alone was 1.06, with an upper 90%
      CI of 1.07 (below non-inferiority margin of 1.50). Ratio for bleeding time for
      aspirin with sugammadex vs. aspirin plus placebo was 1.20, with upper 90% CI of
      1.45 (below non-inferiority margin of 1.50). Sugammadex was generally well
      tolerated. CONCLUSION: There was no clinically relevant reduction in platelet
      aggregation with addition of sugammadex 4 mg/kg to aspirin. Pre-determined non
      inferiority margins were not exceeded for bleeding time and APTT.

PMID- 24120719
TI  - Adherence in tamoxifen therapy after conversion to a rebate pharmaceutical in
      breast cancer patients in Germany.
AB  - BACKGROUND: The aim of this study was to investigate the risk of therapy
      discontinuation in breast cancer patients treated with tamoxifen with and without
      conversion to a rebate pharmaceutical (tamoxifen) and to analyze the negative
      consequences of rebate contracts on the compliance of breast cancer patients
      among gynecologist and general practitioner practices in Germany. METHODS: This
      retrospective analysis was performed using the IMS Disease Analyzer(r) database.
      Women with a diagnosis of breast cancer and first time prescription of tamoxifen
      in the time from January 2008 until December 2011 were selected. Main outcome
      measure was the incident the hormone treatment discontinuation rates within 3
      years after index date. Treatment discontinuation of tamoxifen was defined as 90
      days without this or alternative hormonal therapy (aromatase inhibitors) during
      that time. RESULTS: In total, 3,620 patients were included in the persistence
      analysis. 1,712 (47.3%) patients were converted to a rebate product. Within 3
      years of follow-up, the discontinuation rates increased to 51.5% for switched
      patients and 46.3% for patients without switch (p < 0.01). Hazard ratios for 3
      year risk of tamoxifen therapy discontinuation were adjusted for age, sex,
      gynecologist care, patient and physician's residency, baseline co-morbidities
      (osteoporosis, diabetes, depression and thrombosis, side effects). These analyses
      comprised a significantly increased risk for treatment discontinuation for
      patients who were switched to a rebate pharmaceutical compared to patients
      without conversion to a rebate pharmaceutical (HR: 1.27, CI: 1.05 - 1.53, p =
      0.014). CONCLUSIONS: This analysis underlines an association between the
      initiation of rebate contracts and a negative impact on the compliance of breast
      cancer patients on an adjuvant hormonal treatment The impact of rebate contracts
      on the health of patients and the health care costs should be evaluated in
      further therapeutic fields through additional research projects. *both authors
      contributed equally to the manuscript.

PMID- 24120720
TI  - Changes in the function and expression of T-type and N-type calcium channels in
      the rat bladder after bladder outlet obstruction.
AB  - PURPOSE: We evaluated possible changes in the function and expression of T-type
      and N-type Ca(2+) channels in the bladder of rats with bladder outlet
      obstruction. MATERIALS AND METHODS: Female Sprague Dawley(r) rats were divided
      into a group with bladder outlet obstruction created by partial urethral ligation
      and a sham operated group. Six weeks postoperatively we determined the mRNA
      expression of T-type and N-type Ca(2+) channels in the bladder, dorsal root
      ganglion and spinal cord. We also cystometrically investigated expression by
      intravenous administration of the T-Ca blocker RQ-00311610 or the N-type Ca(2+)
      channel blocker omega-conotoxin GVIA. We then performed in vitro functional
      studies of detrusor strips using these blockers. RESULTS: mRNA expression of T
      type Ca(2+) channels in the bladder detrusor and mucosa layers, and the spinal
      cord dorsal horn, and N-type Ca(2+) channels in the whole bladder and detrusor
      layer, and the spinal cord dorsal horn was greater in the obstructed group than
      the sham operated group. In obstructed rats bladder capacity and voided volume
      increased after RQ-00311610 administration but the number of nonvoiding
      contractions decreased after omega-conotoxin GVIA administration. Detrusor strips
      from obstructed rats showed weaker contractile responses to electrical field
      stimulation, particularly in regard to the purinergic component. omega-Conotoxin
      GVIA suppressed electrical field stimulation induced contractions only in the
      detrusor of obstructed rats, especially the cholinergic component. CONCLUSIONS:
      Blocking T-type Ca(2+) channels increased bladder capacity while N-type Ca(2+)
      channel blockade inhibited nonvoiding contractions in rats with bladder outlet
      obstruction. Decreased bladder efferent neurotransmission occurred after bladder
      outlet obstruction, predominantly in its purinergic component and detrusor
      contractions via cholinergic neurotransmission were activated in a compensatory
      manner, probably via N-type Ca(2+) channel up-regulation.

PMID- 24120722
TI  - Distal hypospadias: circumcision vs preputial reconstruction.

PMID- 24120724
TI  - Intrauterine testicular torsion.

PMID- 24120725
TI  - Scalable biocatalytic synthesis of optically pure ethyl (R)-2-hydroxy-4
      phenylbutyrate using a recombinant E. coli with high catalyst yield.
AB  - Ethyl (R)-2-hydroxy-4-phenylbutanoate [(R)-HPBE] is a versatile and important
      chiral intermediate for the synthesis of angiotensin-converting enzyme (ACE)
      inhibitors. Recombinant E. coli strain coexpressing a novel NADPH-dependent
      carbonyl reductase gene iolS and glucose dehydrogenase gene gdh from Bacillus
      subtilis showed excellent catalytic activity in (R)-HPBE production by asymmetric
      reduction. IolS exhibited high stereoselectivity (>98.5% ee) toward alpha
      ketoesters substrates, whereas fluctuant ee values (53.2-99.5%) for beta
      ketoesters with different halogen substitution groups. Strategies including
      aqueous/organic biphasic system and substrate fed-batch were adopted to improve
      the biocatalytic process. In a 1-L aqueous/octanol biphasic reaction system, (R)
      HPBE was produced in 99.5% ee with an exceptional catalyst yield (g product/g
      catalyst) of 31.7 via bioreduction of ethyl 2-oxo-4-phenylbutyrate (OPBE) at 330
      g/L.

PMID- 24120726
TI  - L-lactic acid production by Bacillus subtilis MUR1 in continuous culture.
AB  - A novel UV-induced mutant strain of recombinant Bacillus subtilis MUR1 was used
      for the production of L-LA in continuous cultures with a variety of culture
      conditions. The maximal productivity of 17.6g/L/h was obtained with a L-LA
      concentration of 44.1g/L at the dilution rate of 0.4h(-1). The highest
      concentration of L-LA (77.1g/L) was produced at the dilution rate of 0.05 h(-1).
      This study showed that the maximum L-LA productivity of B. subtilis MUR1 which
      can only last for a very short period of time during the exponential phase in fed
      batch cultures, can be extended indefinitely at steady state in continuous
      cultures. L-LA production increased with the increase of yeast extract
      concentrations in the medium. Moreover, temperature, agitation rate and various
      glucose concentrations in the feed were compared in continuous cultures.
      Different nitrogen sources (lysine, glutamine, ammonium sulphate and corn steep
      liquor) were studied to partly or completely replace yeast extract in the medium,
      most of them showed positive effects on L-LA production and cell growth. The L-LA
      productivities from continuous cultures in this study are higher than the
      productivity of current microbial industrial processes which use Lactobacillus to
      produce L-LA.

PMID- 24120727
TI  - A physiologically based pharmacokinetics model for melatonin--effects of light
      and routes of administration.
AB  - Physiologically based pharmacokinetic (PBPK) models were developed using MATLAB
      Simulink((r)) to predict diurnal variations of endogenous melatonin with light as
      well as pharmacokinetics of exogenous melatonin via different routes of
      administration. The model was structured using whole body, including pineal and
      saliva compartments, and parameterized based on the literature values for
      endogenous melatonin. It was then optimized by including various intensities of
      light and various dosage and formulation of melatonin. The model predictions
      generally have a good fit with available experimental data as evaluated by mean
      squared errors and ratios between model-predicted and observed values considering
      large variations in melatonin secretion and pharmacokinetics as reported in the
      literature. It also demonstrates the capability and usefulness in simulating
      plasma and salivary concentrations of melatonin under different light conditions
      and the interaction of endogenous melatonin with the pharmacokinetics of
      exogenous melatonin. Given the mechanistic approach and programming flexibility
      of MATLAB Simulink((r)), the PBPK model could provide predictions of endogenous
      melatonin rhythms and pharmacokinetic changes in response to environmental
      (light) and experimental (dosage and route of administration) conditions.
      Furthermore, the model may be used to optimize the combined treatment using light
      exposure and exogenous melatonin for maximal phase advances or delays. 

PMID- 24120728
TI  - Towards the characterization of an in vitro triple co-culture intestine cell
      model for permeability studies.
AB  - Caco-2 based cell models have been the gold standard in vitro method to study
      intestinal drug permeability, despite the absence of many important features with
      major influence in the drug absorption mechanism. In the present work, a triple
      co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic
      in a closely way the human intestinal epithelium, presenting the main components
      in the process of drug absorption, namely the absorptive cells that resemble
      enterocytes, mucus producers cells and cells able to induce M-cell phenotype on
      Caco-2 cells. All the three cell lines maintained their function when cultured
      together with each other being, thus, an asset to new orally administrated drugs
      development. The seeding ratio of 90:10 between Caco-2 and HT29-MTX showed to be
      the best to achieve physiological proportions after cells maturation and
      differentiation in culture. The formation of M-cells phenotype from enterocytes
      was identified for the first time in a co-culture system comprising Caco-2 and
      HT29-MTX cells through immunocytochemical techniques. Thus, the triple co-culture
      model presented in the herein work is a good and reliable alternative to the in
      vitro methods already existents for the study of drugs permeability. 

PMID- 24120729
TI  - Effects of particle size on the pharmacokinetics of puerarin nanocrystals and
      microcrystals after oral administration to rat.
AB  - Puerarin, which is extracted from traditional Chinese medicine, is widely used in
      clinic in China and mainly used as a therapeutic agent to cardiovascular
      diseases. Owing to its poor water solubility and adverse drug reactions caused by
      cosolvents after intravenous administration, the development of oral formulation
      is urgently needed. Nowadays, nanocrystals technique has become a preferred way
      to develop oral dosage form. In this study, we used high pressure homogenization
      (HPH) to prepare puerarin nanocrystals and microcrystals with different sizes
      ranged from 525.8 nm to 1875.6 nm and investigated the influence of particle size
      on pharmacokinetics. The nanocrystals and microcrystals prepared were
      characterized using DLS, DSC, XRD and SEM, and we found that the crystalline
      state of puerarin was changed during the preparation process and the drug was
      dispersed into HPMC. In the pharmacokinetic study, we observed an increasing of
      Cmax and AUC and a decreasing of CL/F with the decreasing of particle size. The
      AUC of the puerarin nanocrystals (525.8 nm) was 7.6-fold of that of raw puerarin
      suspension, with an absolute bioavailability of 21.44%. From the above results,
      we can conclude that nanocrystal technique is an efficient technology to improve
      the oral bioavailability of puerarin.

PMID- 24120730
TI  - Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression
      in primary human hepatocytes and human cancer cells.
AB  - Food constituents may cause a phenomenon of food-drug interactions. In the
      current study, we examined the effects of artificial sweeteners (aspartame,
      acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and
      glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes,
      hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in
      concentrations up to those occurring in non-alcoholic beverages. Basal and ligand
      inducible AhR- and GR-dependent reporter gene activation in stably transfected
      HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners
      tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in
      primary cultures of human hepatocytes and in LS174T and HepG2 cells was not
      induced by any of the tested sweeteners. Overall, aspartame, acesulfame,
      saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional
      activities of AhR and GR. These data imply the safety of artificial sweeteners in
      terms of interference with AhR, GR and CYP1A1. 

PMID- 24120731
TI  - An Epstein-Barr virus-positive diffuse large B-cell lymphoma presenting as multi
      organ failure: a catastrophic lymphomatosis with fulminant visceral organ
      dissemination resulting in a precipitous death in a 59-year-old female with no
      identifiable etiology for immunodeficiency.
AB  - Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of
      the elderly is an aggressive B-cell neoplasm related to age-associated impaired
      immunity. We report such a case in a 59-year-old woman with a catastrophic
      disease course. The patient initially presented with fever, fatigue, malaise and
      weakness over one-week period. Despite empirical treatment with antibiotics and
      antiviral agents, she subsequently developed multi-organ failure and
      coagulopathy. Radiographic imaging revealed hepatomegaly, splenomegaly, pleural
      effusion, and ascites. Her complete blood cell count showed marked leukocytosis,
      anemia and thrombocytopenia. Morphologic examination of blood smear demonstrated
      many abnormal plasmacytoid lymphocytes, and flow cytometric analysis detected an
      intermediate-large mature B-cell population (69%) without detectable surface
      immunoglobulin. High copy numbers of EBV genome were detected in the blood by
      PCR. A diagnosis of EBV+ DLBCL, leukemic phase, was made. Despite aggressive
      treatment and supportive care, the patient succumbed to multi-organ failure one
      week after initial presentation. Autopsy demonstrated EBV+ DLBCL infiltration in
      all the organs examined. This case describes an unusual presentation of EBV+
      DLBCL and highlights the necessity of pertinent ancillary tests to avoid delay in
      the diagnosis and treatment. 

PMID- 24120732
TI  - Systems approaches in understanding evolution and evolvability.
AB  - Systems and network-based approaches are becoming increasingly popular in
      cellular biology. One contribution of such approaches has been to shed some light
      on the evolutionary origins of core organisational principles in biological
      systems, such as modularity, robustness, and evolvability. Models of interactions
      between genes (epistasis) have also provided insight into how sexual reproduction
      may have evolved. Additionally, recent work on viewing evolution as a form of
      learning from the environment has indicated certain bounds on the complexity of
      the genetic circuits that can evolve within feasible quantities of time and
      resources. Here we review the key studies and results in these areas, and discuss
      possible connections between them. In particular, we speculate on the link
      between the two notions of 'evolvability': the evolvability of a system in terms
      of how agile it is in responding to novel goals or environments, and the
      evolvability of certain kinds of gene network functionality in terms of its
      computational complexity. Drawing on some recent work on the complexity of graph
      theoretic problems on modular networks, we suggest that modularity as an
      organising principle may have its raison d'etre in its ability to enhance
      evolvability, in both its senses. 

PMID- 24120733
TI  - Implementing vertex dynamics models of cell populations in biology within a
      consistent computational framework.
AB  - The dynamic behaviour of epithelial cell sheets plays a central role during
      development, growth, disease and wound healing. These processes occur as a result
      of cell adhesion, migration, division, differentiation and death, and involve
      multiple processes acting at the cellular and molecular level. Computational
      models offer a useful means by which to investigate and test hypotheses about
      these processes, and have played a key role in the study of cell-cell
      interactions. However, the necessarily complex nature of such models means that
      it is difficult to make accurate comparison between different models, since it is
      often impossible to distinguish between differences in behaviour that are due to
      the underlying model assumptions, and those due to differences in the in silico
      implementation of the model. In this work, an approach is described for the
      implementation of vertex dynamics models, a discrete approach that represents
      each cell by a polygon (or polyhedron) whose vertices may move in response to
      forces. The implementation is undertaken in a consistent manner within a single
      open source computational framework, Chaste, which comprises fully tested,
      industrial-grade software that has been developed using an agile approach. This
      framework allows one to easily change assumptions regarding force generation and
      cell rearrangement processes within these models. The versatility and generality
      of this framework is illustrated using a number of biological examples. In each
      case we provide full details of all technical aspects of our model
      implementations, and in some cases provide extensions to make the models more
      generally applicable. 

PMID- 24120734
TI  - IntApop: a web service for predicting apoptotic protein interactions in humans.
AB  - Apoptosis, a type of cell death, is necessary for maintaining tissue homeostasis
      and removing malignant cells. Interrupted apoptosis process contributes to
      carcinogenesis, developmental defects, autoimmune diseases and neurological
      disorders. Due to the complexity of the process, the molecular dynamics and
      relative interactions of individual proteins responsible for the activation or
      inhibition of apoptosis should be researched systematically. In this study, we
      integrate known protein interactions from databases DIP, IntAct, MINT, HPRD and
      BioGRID by Naive Bayes classifier. The receiver operation characteristic (ROC)
      curve with the area under the ROC curve (AUC) of 0.797 indicates it has a good
      performance in prediction. Then, we predict the global human apoptotic protein
      interactions network. Within it, we not only identify the already known
      interactions of caspases (caspase-8/-10, caspase-9, caspase-3/-6/-7) and Bcl-2
      family, but also reveal that Bid can interact with casein kinases (CSK21/22/2B,
      KC1A, KC1E); both of B2LA1 and B2CL2 can interact with Bid, Bax and Bak; caspase
      8 interacts with autophagic proteins (MLP3B, MLP3A and LRRk2). Consequently, we
      make an initial step to develop the web service IntApop that provides an
      appropriate platform for apoptosis researchers, systems biologists and
      translational clinician scientists to predict apoptotic protein interactions in
      human. In addition, the interaction network can be visualized online, making it a
      widely applicable systems biology tool for apoptosis and cancer researchers. 

PMID- 24120735
TI  - Metabolic pathways recruited in the production of a recombinant enveloped virus:
      mining targets for process and cell engineering.
AB  - Biopharmaceuticals derived from enveloped virus comprise an expanding market of
      vaccines, oncolytic vectors and gene therapy products. Thus, increased attention
      is given to the development of robust high-titer cell hosts for their
      manufacture. However, the knowledge on the physiological constraints modulating
      virus production is still scarce and the use of integrated strategies to improve
      hosts productivity and upstream bioprocess an under-explored territory. In this
      work, we conducted a functional genomics study, including the transcriptional
      profiling and central carbon metabolism analysis, following the metabolic changes
      in the transition 'parental-to-producer' of two human cell lines producing
      recombinant retrovirus. Results were gathered into three comprehensive metabolic
      maps, providing a broad and integrated overview of gene expression changes for
      both cell lines. Eight pathways were identified to be recruited in the virus
      production state: amino acid catabolism, carbohydrate catabolism and integration
      of the energy metabolism, nucleotide metabolism, glutathione metabolism, pentose
      phosphate pathway, polyamines biosynthesis and lipid metabolism. Their ability to
      modulate viral titers was experimentally challenged, leading to improved specific
      productivities of recombinant retrovirus up to 6-fold. Within recruited pathways
      in the virus production state, we sought for metabolic engineering gene targets
      in the low producing phenotypes. A mining strategy was used alternative to the
      traditional approach 'high vs. low producer' clonal comparison. Instead, 'high
      vs. low producer' from different genetic backgrounds (i.e. cell origins) were
      compared. Several genes were identified as limiting in the low-production
      phenotype, including two enzymes from cholesterol biosynthesis, two enzymes from
      glutathione biosynthesis and the regulatory machinery of polyamines biosynthesis.
      This is thus a frontier work, bridging fundamentals to technological research and
      contributing to enlarge our understanding of enveloped virus production dynamics
      in mammalian cell hosts. 

PMID- 24120736
TI  - Context dependent reversion of tumor phenotype by connexin-43 expression in MDA
      MB231 cells and MCF-7 cells: role of beta-catenin/connexin43 association.
AB  - Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors,
      and Cx43 expression is often down regulated in breast tumors. We assessed the
      effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma
      cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased
      proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB
      231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D
      cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected
      MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells
      formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed
      smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar
      morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced
      by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells,
      nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D
      cultures, and disrupted acinar morphology. Although Cx43 over-expression did not
      affect total levels of beta-catenin, alpha-catenin and ZO-2, it decreased nuclear
      levels of beta-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures
      of MDA-MB-231 cells. Cx43 associated at the membrane with alpha-catenin, beta
      catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions
      in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive
      effects in a context-dependent manner where GJ assembly with alpha-catenin, beta
      catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and,
      malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA
      MB-231 cells, by sequestering beta-catenin away from nucleus. 

PMID- 24120737
TI  - Tolerogenic dendritic cell vaccines to treat autoimmune diseases: can the
      unattainable dream turn into reality?
AB  - Autoimmune diseases affect about one in 15 individuals in developed countries and
      are characterized by a breakdown in immune tolerance. Current therapeutic
      approaches against destructive immune responses in autoimmune diseases are based
      on non-specific agents systemically suppressing the function of many immune
      effector cells. This indiscriminate immunosuppression, however, often causes
      serious and sometimes life-threatening side effects. Therefore, the need for more
      specific treatments resulting in lower toxicity and longer-term solutions is
      high. Because of the established role of dendritic cells (DCs) in maintaining the
      balance between immunity and tolerance, tolerogenic (tol)DCs might be novel
      therapeutic targets to prevent undesirable (auto-)immune responses. The idea
      behind tolDC therapy is that it is a highly targeted, antigen-specific treatment
      that only affects the auto-reactive inflammatory response. The therapeutic
      potential of tolDCs has already been proven in experimental animal models of
      different autoimmune disorders as well as with in vitro experiments using ex vivo
      generated human tolDCs, thus the challenge remains in bringing tolDC therapy to
      the clinic, although first clinical trials have been conducted. In this review,
      we will extensively discuss the use of tolDCs for induction of antigen-specific
      tolerance in several autoimmune disease settings, from bench to bedside,
      including currently applied strategies to generate tolDCs as well as technical
      difficulties and challenges in the field. 

PMID- 24120738
TI  - Association of osteopontin polymorphisms with nasopharyngeal carcinoma risk.
AB  - No previous study has reported the association of osteopontin polymorphisms with
      nasopharyngeal carcinoma (NPC) risk. We aimed to investigate the association in a
      Chinese population. Four variants of osteopontin, rs11730582, rs1126772, rs9138,
      and rs4754 polymorphisms, were assessed in a case-control study which consists of
      108 NPC patients and 210 health controls, by using polymerase chain reaction-
      restriction fragment length polymorphism method. Serum osteopontin levels were
      measured by enzyme-linked immunosorbent assay. The serum osteopontin levels were
      significantly higher in NPC patients than those in controls (P<0.01). Carriers of
      CC and CT genotype of rs11730582 presented lower serum osteopontin levels than
      those of TT genotype carriers (P<0.05). Genotypes CT and CT+CC of rs11730582 were
      associated with the risk of NPC (CT:OR = 0.57, 95%CI = 0.34-0.94; CC+CT:OR =
      0.54, 95%CI = 0.34-0.87). Haplotype analysis revealed that haplotype T-A-A-C of
      rs11730582, rs1126772, rs9138, and rs4754 was associated with NPC risk (OR =
      0.49, 95%CI = 0.27-0.86). Stratification analysis showed that genotypes CT and
      CT+CC of rs11730582 were associated with tumor stage and lymph node metastasis
      (P<0.05). No associations were found between rs1126772, rs9138, and rs4754
      polymorphisms and NPC risk (P>0.05). The variant rs11730582 of osteopontin is
      associated with NPC risk. It potentially serves as a genetic marker of NPC
      predisposition.

PMID- 24120739
TI  - Decreased expression of toll like receptor signaling molecules in chronic HBV
      infected patients.
AB  - INTRODUCTION: Toll like receptors (TLRs) and their signaling molecules play
      important roles in microbe recognition and induction of immune responses,
      including production of inflammatory cytokines, against viral infections.
      Therefore, the aim of this study was to examine expression levels of TLR
      signaling molecules (IRAK1, IRAK4, TRAF3, and IRF7) and the pro-inflammatory
      cytokines, IL-12 and IL-6 in chronic HBV infected (CHB) patients. DESIGN: This
      study was performed on 60 CHB patients and 60 healthy controls and the expression
      of IRAK1, IRAK4, TRAF3, and IRF7 and their downstream inflammatory cytokines (IL
      12 and IL-6) were evaluated by Real-Time PCR and ELISA techniques. RESULTS: The
      results demonstrated that expression of IRAK4, TRAF3, and IRF7 were significantly
      decreased in PBMCs of CHB patients in comparison to healthy controls. Serum
      levels of IL-12 were significantly increased, while, IL-6 were not differ between
      patients and controls. CONCLUSIONS: Based on the results presented here it seems
      that CHB patients do not express appropriate levels of the genes in the TLRs
      pathway which may lead to impaired immune responses against HBV infection which
      is seen in the patients.

PMID- 24120742
TI  - Structural insights into transcription initiation by RNA polymerase II.
AB  - Transcriptional regulation is one of the most important steps in control of cell
      identity, growth, differentiation, and development. Many signaling pathways
      controlling these processes ultimately target the core transcription machinery
      that, for protein coding genes, consists of RNA polymerase II (Pol II) and the
      general transcription factors (GTFs). New studies on the structure and mechanism
      of the core assembly and how it interfaces with promoter DNA and coactivator
      complexes have given tremendous insight into early steps in the initiation
      process, genome-wide binding, and mechanisms conserved for all nuclear and
      archaeal Pols. Here, we review recent developments in dissecting the architecture
      of the Pol II core machinery with a focus on early and regulated steps in
      transcription initiation. 

PMID- 24120744
TI  - Human epidermal stem cell function is regulated by circadian oscillations.
AB  - Human skin copes with harmful environmental factors that are circadian in nature,
      yet how circadian rhythms modulate the function of human epidermal stem cells is
      mostly unknown. Here we show that in human epidermal stem cells and their
      differentiated counterparts, core clock genes peak in a successive and phased
      manner, establishing distinct temporal intervals during the 24 hr day period.
      Each of these successive clock waves is associated with a peak in the expression
      of subsets of transcripts that temporally segregate the predisposition of
      epidermal stem cells to respond to cues that regulate their proliferation or
      differentiation, such as TGFbeta and calcium. Accordingly, circadian arrhythmia
      profoundly affects stem cell function in culture and in vivo. We hypothesize that
      this intricate mechanism ensures homeostasis by providing epidermal stem cells
      with environmentally relevant temporal functional cues during the course of the
      day and that its perturbation may contribute to aging and carcinogenesis.

PMID- 24120743
TI  - Dynamic analysis of gene expression and genome-wide transcription factor binding
      during lineage specification of multipotent progenitors.
AB  - We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic
      relationships between transcription factor (TF) binding and global gene
      expression programs as multipotent cells differentiate. We combined global ChIP
      seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to
      erythroid and neutrophil lineages. Our analysis reveals (1) differential
      complexity of sequence motifs bound by GATA1, GATA2, and PU.1; (2) the scope and
      interplay of GATA1 and GATA2 programs within, and during transitions between,
      different cell compartments, and the extent of their hard-wiring by DNA motifs;
      (3) the potential to predict gene expression trajectories based on global
      associations between TF-binding data and target gene expression; and (4) how
      dynamic modeling of DNA-binding and gene expression data can be used to infer
      regulatory logic of TF circuitry. This rubric exemplifies the utility of this
      cross-platform resource for deconvoluting the complexity of transcriptional
      programs controlling stem/progenitor cell fate in hematopoiesis. 

PMID- 24120745
TI  - [Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology].
AB  - BACKGROUND: Lean Six Sigma methodology has been used to improve care processes,
      eliminate waste, reduce costs, and increase patient satisfaction. OBJECTIVE: To
      analyse the results obtained with Lean Six Sigma methodology in the diagnosis and
      improvement of the inpatient pharmacotherapy process during structural and
      organisational changes in a tertiary hospital. MATERIAL AND METHODS:  SCOPE:
      1.000 beds tertiary hospital. DESIGN: prospective observational study. The
      define, measure, analyse, improve and control (DMAIC), were deployed from March
      to September 2011. An Initial Project Charter was updated as results were
      obtained. POPULATION AND SAMPLE: 131 patients with treatments prescribed within
      24h after admission and with 4 drugs. VARIABLES: safety indicators (medication
      errors), and efficiency indicators (complaints and time delays). RESULTS:
      Proportion of patients with a medication error was reduced from 61.0% (25/41
      patients) to 55.7% (39/70 patients) in four months. Percentage of errors
      (regarding the opportunities for error) decreased in the different phases of the
      process: Prescription: from 5.1% (19/372 opportunities) to 3.3% (19/572
      opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847
      opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0%
      (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038
      patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800
      euros saved. CONCLUSIONS: An improvement in the pharmacotherapeutic process and a
      positive economic impact was observed, as well as enhancing patient safety and
      efficiency of the organization. Standardisation and professional training are
      future Lean Six Sigma candidate projects.

PMID- 24120746
TI  - Effects of Hibiscus sabdariffa L. on serum lipids: a systematic review and meta
      analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Prevention of cardiovascular disease by modifying
      its major risk factors, including serum cholesterol levels, is an important
      strategy. Hibiscus sabdariffa L. has been promoted for reducing cholesterol
      levels, but its reported impact on cholesterol levels has been inconsistent. The
      study aimed to assess systematically the evidence and quality of current research
      on the effect of Hibiscus sabdariffa L. on blood lipids and its adverse effects.
      MATERIALS AND METHODS: Electronic databases were searched up to June 2013 for
      relevant randomised controlled trials (RCTs). Journals and conference proceedings
      were also searched. The quality of the selected trials was assessed using the
      Cochrane Risk of Bias Assessment Tool. The efficacy results of similar studies
      were pooled if they used the same comparator. Outcomes examined were levels of
      total cholesterol, high density lipoprotein cholesterol, low density lipoprotein
      cholesterol and triglycerides. RESULTS: Six studies involving 474 subjects met
      our inclusion criteria. These studies varied in terms of the types of
      interventions, comparators used, and duration of trials. Overall, Hibiscus
      sabdariffa L. did not produce any significant effect on any of the outcomes
      examined, when compared with placebo, black tea or diet. With short-term use it
      is well tolerated. CONCLUSIONS: The available evidence from RCTs does not support
      the efficacy of Hibiscus sabdariffa L. in lowering serum lipids. Further
      rigorously designed trials with larger sample sizes are warranted to confirm the
      effects of HS on serum lipids.

PMID- 24120747
TI  - An ethnobotanical survey of indigenous medicinal plants in Wana district south
      Waziristan agency, Pakistan.
AB  - ETHNOMEDICINAL RELEVANCE: Medicinal plants are treasure of any region for ailment
      treatment. The present research work was focused to document the indigenous
      knowledge of unexplored area of Wana, South Waziristan Agency, Pakistan. This was
      the very first study, to explore the potential ethno-medicinal plants of study
      area. MATERIALS AND METHODS: Data was collected by opting people participation
      involving interviews, group meetings, semi structured discussions and filling of
      questionnaires. RESULTS AND DISCUSSION: A total 50 wild medicinal plants
      belonging to 30 families were collected. Medicinal plants used against the
      stomach disorders were 10% followed by the cold/cough (8%), hepatitis (7%),
      diuretic (7%), sedative/narcotic (7%), tonic (6%), asthma (5%), cardiac problems
      (4%), jaundice (4%) and so on. Among plant parts used for indigenous medicines,
      leaves were (24%) followed by the fruit (15%), root (12%), seed (11%), whole
      plant (9%), arial parts (8%), flower (6%), rhizome, bark and stem (4%), bulbs
      (2%) and pods (1%). Xanthium strumarium reported the highest use value i.e. 0.95.
      CONCLUSION: People of Wana still rely on indigenous plants for their basic
      healthcare needs. Harvesting of roots and whole plants is a big threat to
      conservation of medicinal plants diversity.

PMID- 24120748
TI  - Skin microvascular response to pressure load in obese mice.
AB  - PURPOSE: The role of obesity in the appearance of skin pressure ulcers remains
      controversial. The aim of the present study was to evaluate blood perfusion and
      related lesions after skin compression in obese mice. METHODS: Sixty C57BL6 male
      mice were randomly assigned to a control or hypercalorific diet (HCD) for 2, 4
      and 12weeks. Skin compression was induced by a magnetic force of 11 kPa overlying
      a subcutaneous metal plate and applied for 4h. Skin perfusion was examined using
      laser Doppler imaging before skin compression, immediately after compression
      release and 24h later. 24h after magnet removal, skin injuries were determined by
      photography. RESULTS: A heterogeneous distribution of blood perfusion was
      observed using the colour-coded map of the skin perfusion on the compressed area.
      At 24-h post-compression release, 60% to 75% of the compressed area was ischaemic
      in the 2-week HCD group and in all the control groups compared to 35% in the 4-
      and 15% in the 12-week HCD groups. The lowest occurrence of skin lesion seen as
      skin redness or pressure-sores was observed in the 12- week HCD group (4%)
      compared to about 12% in either the control or the 2- and 4-week HCD groups.
      CONCLUSIONS: This study suggests that there was no clear relationship between the
      extent of ischaemia and skin lesion occurrence after skin compression in short
      duration obese mice. In contrast, it appears that long-duration obesity could
      reduce both ischaemia and skin lesions in response to skin compression through
      changes in skin structure.

PMID- 24120749
TI  - Systematic review: insufficient validation of clinical scores for the assessment
      of acute dyspnoea in wheezing children.
AB  - BACKGROUND: A reliable, valid, and easy-to-use assessment of the degree of wheeze
      associated dyspnoea is important to provide individualised treatment for children
      with acute asthma, wheeze or bronchiolitis. OBJECTIVE: To assess validity,
      reliability, and utility of all available paediatric dyspnoea scores. METHODS:
      Systematic review. We searched Pubmed, Cochrane library, National Guideline
      Clearinghouse, Embase and Cinahl for eligible studies. We included studies
      describing the development or use of a score, assessing two or more clinical
      symptoms and signs, for the assessment of severity of dyspnoea in an acute
      episode of acute asthma, wheeze or bronchiolitis in children aged 0-18 years. We
      assessed validity, reliability and utility of the retrieved dyspnoea scores using
      15 quality criteria. RESULTS: We selected 60 articles describing 36 dyspnoea
      scores. Fourteen scores were judged unsuitable for clinical use, because of
      insufficient face validity, use of items unsuitable for children, difficult
      scoring system or because complex auscultative skills are needed, leaving 22
      possibly useful scores. The median number of quality criteria that could be
      assessed was 7 (range 6-11). The median number of positively rated quality
      criteria was 3 (range 1-5). Although most scores were easy to use, important
      deficits were noted in all scores across the three methodological quality
      domains, in particular relating to reliability and responsiveness. CONCLUSION:
      None of the many dyspnoea scores has been sufficiently validated to allow for
      clinically meaningful use in children with acute dyspnoea or wheeze. Proper
      validation of existing scores is warranted to allow paediatric professionals to
      make a well balanced decision on the use of the dyspnoea score most suitable for
      their specific purpose.

PMID- 24120750
TI  - p53 is involved in shrimp survival via its regulation roles on MnSOD and GPx in
      response to acute environmental stresses.
AB  - The tumor suppressor gene p53 plays a critical role in safeguarding the integrity
      of genome in mammalian cells. It acts as a sequence-specific transcription
      factor. Once activated by a variety of cellular stresses, p53 transactivates
      downstream target genes, through which it regulates cell cycle and apoptosis.
      However, little is known about p53 as well as its downstream target genes in
      invertebrates. A full length cDNA that encodes a 453-amino-acid p53 protein
      (Lvp53) was characterized in the Pacific white shrimp (Litopenaeus vannamei) to
      explore the potential relationships between p53 and two antioxidant enzyme genes:
      Mn-superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) in eliminating
      cell stresses in L. vannamei. Sequence analysis revealed a close phylogenetic
      relationship between Lvp53 and that of Marsupenaeus japonicus, and a high degree
      of conservation in critical amino acids residues is involved in DNA and zinc
      binding among species. Quantitative real-time PCR showed that Lvp53 was expressed
      with varied levels in all the 11 tissues under investigation. In response to
      acute pH challenge, the relative expression of Lvp53 was induced in a pH- and
      time-dependent manner, with the peak observed at pH 6.1 and after 24 h of
      treatment, in which condition, both the relative mRNA expressions and the
      enzymatic activities of LvMnSOD and LvGPx were increased correspondingly. In
      response to acute cadmium (Cd) exposure, the relative expression of Lvp53 was
      upregulated in a time- and concentration-dependent manner, with the maximum
      detected at Cd 6.6 MUM and after 48 h of exposure, in which case, both the
      transcripts and the enzymatic activities of LvMnSOD and LvGPx were also induced.
      After Lvp53 transcripts were declined by double-strand RNA injection, the
      relative mRNA expressions of LvMnSOD and LvGPx were decreased correspondingly.
      Meanwhile, pH 6.1 or 6.6 MUM Cd could not induce the transcripts or the enzymatic
      activities of LvMnSOD or LvGPx any more in Lvp53-silenced shrimp, but increased
      shrimp mortalities. These results indicated the involvement of Lvp53, LvMnSOD and
      LvGPx in mediating cell stress caused by suboptimal pH and elevated levels of Cd
      in L. vannamei, and that the expressions of LvMnSOD and LvGPx were positively
      regulated by Lvp53, which is a potential mechanism for shrimp to survive the
      oxidative stress that occurs during short-term exposure to Cd or challenge with
      acidic pH. This finding will contribute to better understanding of p53 signaling
      pathways and redox regulation in invertebrate organisms.

PMID- 24120752
TI  - Autoantibodies in neuroimmunological diseases; relevance of fine specificity.
AB  - Autoantibodies are involved in the pathogenesis of several neuroimmunological
      diseases. Anti-neurofascin antibodies are detected in sera from some patients
      with multiple sclerosis and have been shown to induce axonal damage and
      exacerbation of experimental autoimmune encephalomyelitis. Recently, Lindner et
      al. reported a discrepancy between the activity of the anti-neurofascin
      antibodies in vivo and that in a cell-based assay. This may be due to the effects
      of antibody fine specificity and the local molecular environment of the target
      membrane on the reactivity of the autoantibodies, as reported in diseases such as
      Guillain-Barre syndrome. Thus, an assay system that better reflects the
      environment in vivo is needed to evaluate the pathogenetic roles of
      autoantibodies. 

PMID- 24120751
TI  - A biophysically based mathematical model for the catalytic mechanism of
      glutathione reductase.
AB  - Glutathione reductase (GR) catalyzes the reduction of oxidized glutathione (GSSG)
      to reduced glutathione (GSH) using NADPH as the reducing cofactor, and thereby
      maintains a constant GSH level in the system. GSH scavenges superoxide (O2(*-))
      and hydroxyl radicals (OH) nonenzymatically or by serving as an electron donor to
      several enzymes involved in reactive oxygen species (ROS) detoxification. In
      either case, GSH oxidizes to GSSG and is subsequently regenerated by the
      catalytic action of GR. Although the GR kinetic mechanism has been extensively
      studied under various experimental conditions with variable substrates and
      products, the catalytic mechanism has not been studied in terms of a mechanistic
      model that accounts for the effects of the substrates and products on the
      reaction kinetics. The aim of this study is therefore to develop a comprehensive
      mathematical model for the catalytic mechanism of GR. We use available
      experimental data on GR kinetics from various species/sources to develop the
      mathematical model and estimate the associated model parameters. The model
      simulations are consistent with the experimental observation that GR operates via
      both ping-pong and sequential branching mechanisms based on relevant
      concentrations of its reaction substrate GSSG. Furthermore, we show the observed
      pH-dependent substrate inhibition of GR activity by GSSG and bimodal behavior of
      GR activity with pH. The model presents a unique opportunity to understand the
      effects of products on the kinetics of GR. The model simulations show that under
      physiological conditions, where both substrates and products are present, the
      flux distribution depends on the concentrations of both GSSG and NADP(+), with
      ping-pong flux operating at low levels and sequential flux dominating at higher
      levels. The kinetic model of GR may serve as a key module for the development of
      integrated models for ROS-scavenging systems to understand protection of cells
      under normal and oxidative stress conditions.

PMID- 24120753
TI  - Generation and developmental characteristics of porcine tetraploid embryos and
      tetraploid/diploid chimeric embryos.
AB  - The aim of this study was to optimize electrofusion conditions for generating
      porcine tetraploid (4n) embryos and produce tetraploid/diploid (4n/2n) chimeric
      embryos. Different electric field intensities were tested and 2 direct current
      (DC) pulses of 0.9 kV/cm for 30 MUs was selected as the optimum condition for
      electrofusion of 2-cell embryos to produce 4n embryos. The fusion rate of 2-cell
      embryos and the development rate to blastocyst of presumably 4n embryos, reached
      85.4% and 28.5%, respectively. 68.18% of the fused embryos were found to be 4n as
      demonstrated by fluorescent in situ hybridization (FISH). Although the number of
      blastomeres in 4n blastocysts was significantly lower than in 2n blastocysts
      (P<0.05), there was no significant difference in developmental rates of
      blastocysts between 2n and 4n embryos (P>0.05), suggesting that the blastocyst
      forming capacity in 4n embryos is similar to those in 2n embryos. Moreover, 4n/2n
      chimeric embryos were obtained by aggregation of 4n and 2n embryos. We found that
      the developmental rate and cell number of blastocysts of 4-cell (4n)/4-cell (2n)
      chimeric embryos were significantly higher than those of 2-cell (4n)/4-cell (2n),
      4-cell (4n)/8-cell (2n), 4-cell (4n)/2-cell (2n) chimeric embryos (P<0.05).
      Consistent with mouse chimeras, the majority of 4n cells contribute to the
      trophectoderm (TE), while the 2n cells are mainly present in the inner cell mass
      (ICM) of porcine 4n/2n chimeric embryos. Our study established a feasible and
      efficient approach to produce porcine 4n embryos and 4n/2n chimeric embryos.

PMID- 24120754
TI  - A community-based strength training programme increases muscle strength and
      physical activity in young people with Down syndrome: a randomised controlled
      trial.
AB  - This randomised controlled trial investigated the effects of a student-led
      progressive resistance training (PRT) programme in adolescents and young adults
      with Down syndrome. Sixty-eight young people with Down syndrome (30 female, 38
      male; mean age 17.9+/-2.6 years) and mild to moderate intellectual disability
      were randomly allocated to a PRT programme (n=34) or a social group (n=34).
      Participants in the PRT group trained twice a week for 10 weeks at a community
      gymnasium with a physiotherapy student mentor using pin-loaded weight machines.
      Participants in the social group completed a 10-week programme of social
      activities also with a student mentor once a week for 90 min. Work performance,
      muscle strength and physical activity levels were assessed at weeks 0, 11 and 24
      by an assessor blind to group allocation. Data were analysed using ANCOVA with
      baseline measures as covariate. Participants attended 92% of their scheduled
      sessions. There was no difference between the groups on work task performance.
      The PRT group increased their upper and lower limb strength at week 11 compared
      to the control group, but only their lower limb muscle strength at week 24. There
      was a significant difference in physical activity levels in favour of the PRT
      group at week 24 but not at week 11. PRT using a student mentor model helps young
      people with Down syndrome become stronger and more physically active but its
      effect on work task performance is unclear.

PMID- 24120755
TI  - Submaximal oxygen cost during incremental exercise in children with developmental
      coordination disorder.
AB  - There has been minimal evidence examining the differences in submaximal aerobic
      power between children with and without probable developmental coordination
      disorder (pDCD). This is important as most activities of daily living are
      performed at submaximal levels. The aim of this study was to examine the oxygen
      cost of work (VO2) performed during an incremental exercise protocol on a cycle
      ergometer. Subjects with pDCD (n=63) were matched for age and gender to 63
      typically developing controls (12-13 years of age) using a nested case-control
      design. Motor coordination was assessed using the Movement Assessment Battery for
      Children. Children with pDCD had significantly lower VO2 peak values relative to
      controls (35.0 vs. 42.9 ml/kg/min, p<0.0001). At the submaximal level, mixed
      effects modeling demonstrated that, after controlling for relative body fat, and
      VO2 peak, children with pDCD had consistently greater oxygen cost (VO2 ml/kg/min)
      compared to controls at any given exercise intensity (p=0.0006). A significant
      interaction between pDCD and workload indicated that the difference in VO2 at
      higher workloads is greater than that at lower workloads (p=0.0004). Children
      with pDCD utilize more oxygen to sustain the same submaximal workload. The
      implication of these findings is that children with pDCD may experience earlier
      fatigue than well coordinated individuals when engaging in physical activity.

PMID- 24120756
TI  - The effectiveness of multimedia visual perceptual training groups for the
      preschool children with developmental delay.
AB  - This study compared the effectiveness of three approaches to improving visual
      perception among preschool children 4-6 years old with developmental delays:
      multimedia visual perceptual group training, multimedia visual perceptual
      individual training, and paper visual perceptual group training. A control group
      received no special training. This study employed a pretest-posttest control
      group of true experimental design. A total of 64 children 4-6 years old with
      developmental delays were randomized into four groups: (1) multimedia visual
      perceptual group training (15 subjects); (2) multimedia visual perceptual
      individual training group (15 subjects); paper visual perceptual group training
      (19 subjects); and (4) a control group (15 subjects) with no visual perceptual
      training. Forty minute training sessions were conducted once a week for 14 weeks.
      The Test of Visual Perception Skills, third edition, was used to evaluate the
      effectiveness of the intervention. Paired-samples t-test showed significant
      differences pre- and post-test among the three groups, but no significant
      difference was found between the pre-test and post-test scores among the control
      group. ANOVA results showed significant differences in improvement levels among
      the four study groups. Scheffe post hoc test results showed significant
      differences between: group 1 and group 2; group 1 and group 3; group 1 and the
      control group; and group 2 and the control group. No significant differences were
      reported between group 2 and group 3, and group 3 and the control group. The
      results showed all three therapeutic programs produced significant differences
      between pretest and posttest scores. The training effect on the multimedia visual
      perceptual group program and the individual program was greater than the
      developmental effect Both the multimedia visual perceptual group training program
      and the multimedia visual perceptual individual training program produced
      significant effects on visual perception. The multimedia visual perceptual group
      training program was more effective for improving visual perception than was
      multimedia visual perceptual individual training program. The multimedia visual
      perceptual group training program was more effective than was the paper visual
      perceptual group training program. 

PMID- 24120757
TI  - The immune response of ruminant livestock to bluetongue virus: from type I
      interferon to antibody.
AB  - Infection of ruminants with most (but not all) serotypes of bluetongue virus
      (BTV) leads to a highly blood cell-associated viremia that may be prolonged but
      not persistent. Furthermore, recovered animals are resistant to reinfection with
      the homologous virus serotype, which is the basis for vaccination strategies to
      prevent BTV infection and the clinical disease (bluetongue) that it causes in
      domestic livestock. BTV infection is initiated at the site of virus inoculation
      and the associated draining lymph node, from where the virus is then spread in
      lymph cells to the systemic circulation and secondary sites of replication.
      Replication of BTV in target cells, notably mononuclear phagocytic cells
      (dendritic cells and macrophages) and endothelium, leads to the generation of the
      innate and adaptive immune responses that mediate both initial virus clearance
      and subsequent resistance to infection with the homologous virus serotype. The
      goal of this review is to summarize current understanding of these innate and
      adaptive immune responses of animals to BTV infection. 

PMID- 24120758
TI  - Targeting Mcl-1 for multiple myeloma (MM) therapy: drug-induced generation of Mcl
      1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation.
AB  - Myeloid cell leukemia-1 (Mcl-1, HGNC: 6943), a pro-survival member of the Bcl-2
      family, plays a crucial role in Multiple Myeloma (MM) pathogenesis and drug
      resistance, thus representing a promising therapeutic target in MM. A novel
      strategy to inhibit Mcl-1 activity is the induction of ubiquitin-independent Mcl
      1 degradation. Our own and other previous studies have demonstrated caspase
      dependent generation of a 28kDa Mcl-1 fragment, Mcl-1(128-350), which inhibits MM
      cell proliferation and survival. Here, we show that similar to bortezomib, the
      novel proteasome inhibitors carfilzomib and ixazomib, as well as staurosporine
      and adaphostin, induce the generation of Mcl-1(128-350) in MM cells. Next, the
      molecular sequelae downstream of Mcl-1(128-350), which mediate its pro-apoptotic
      activity, were delineated. Surprisingly, we observed nuclear accumulation of drug
      induced or exogenously overexpressed Mcl-1(128-350), followed by elevated mRNA
      and protein levels of c-Jun, as well as enhanced AP-1 reporter activity.
      Moreover, drug-induced AP-1 activity was blocked after introducing a point
      mutation into the highly conserved Mcl-1 caspase-cleavage site Asp127, but not
      Asp157. Consequently, drug-triggered cell death was significantly decreased in MM
      cells transfected with Mcl-1 D127A, but not with Mcl-1 D157A. Consistent with
      these data, treatment with bortezomib triggered c-Jun upregulation followed by
      apoptosis in Mcl-1(wt/wt), but not Mcl-1(Delta/null) murine embryonic fibroblasts
      (MEFs). Transfection of a plasmid carrying Mcl-1(wt) into Mcl-1(Delta/null) MEFs
      restored bortezomib-induced Mcl-1 fragmentation, c-Jun upregulation and AP-1
      reporter activity. Finally, our data indicate that drug-induced generation of a
      pro-apoptotic Mcl-1 fragment followed by c-Jun upregulation may also be a novel
      therapeutic approach in other tumor entities. 

PMID- 24120759
TI  - Human cytidine deaminases facilitate hepatitis B virus evolution and link
      inflammation and hepatocellular carcinoma.
AB  - During hepatitis B virus (HBV)-induced hepatocarcinogenesis, chronic inflammation
      facilitates the evolution of hepatocellular carcinoma (HCC)-promoting HBV
      mutants. Cytidine deaminases, whose expression is stimulated by inflammatory
      cytokines and/or chemokines, play an important role in bridging inflammation and
      HCC. Through G-to-A hypermutation, cytidine deaminases inhibit HBV replication
      and facilitate the generation of HCC-promoting HBV mutants including C-terminal
      truncated HBx. Cytidine deaminases also promote cancer-related somatic mutations
      including TP53 mutations. Their editing efficiency is counteracted by uracil-DNA
      glycosylase. Understanding the effects of cytidine deaminases in HBV-induced
      hepatocarcinogenesis and HCC progression will aid in developing efficient
      prophylactic and therapeutic strategies against HCC in HBV-infected population. 

PMID- 24120760
TI  - Sustained decrease in plasma sphingosine-1-phosphate concentration and its
      accumulation in blood cells in acute myocardial infarction.
AB  - Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid present at high
      concentration in plasma and blood cells. However, effect of the myocardial
      infarction on S1P metabolism in blood is poorly recognized. Therefore, we aimed
      to examine the dynamics of changes in concentration of sphingolipids in blood of
      patients with acute ST-segment elevation myocardial infarction (STEMI). The study
      was performed on two groups of subjects: healthy controls (n=32) and patients
      with STEMI (n=32). In the latter group blood was taken upon admission to
      intensive heart care unit, and then on the second, fifth and thirtieth day, and
      approximately two years after admission. STEMI patients showed decreased plasma
      S1P concentration and accumulation of free sphingoid bases and their 1-phosphates
      in erythrocytes. This effect was already present upon admission, and was
      maintained for at least thirty days after the infarction. Interestingly, two
      years post-infarction plasma S1P level recovered only partially, whereas the
      content of erythrocyte sphingolipids decreased to the values observed in the
      control subjects. The most likely reason for the observed reduction in plasma S1P
      level was its decreased release or increased degradation by vascular endothelial
      cells, as we did not find any evidence for downregulation of S1P synthesis or
      release by blood cells. We conclude that patients with STEMI are characterized by
      marked alterations in sphingolipid metabolism in blood which could be a
      consequence of the infarction itself, the antiplatelet treatment given or both.
      Our data suggest that cardioprotective action of S1P may be diminished in
      patients with acute myocardial infarction. 

PMID- 24120761
TI  - Crystal structure of an HSA/FcRn complex reveals recycling by competitive mimicry
      of HSA ligands at a pH-dependent hydrophobic interface.
AB  - The long circulating half-life of serum albumin, the most abundant protein in
      mammalian plasma, derives from pH-dependent endosomal salvage from degradation,
      mediated by the neonatal Fc receptor (FcRn). Using yeast display, we identified
      human serum albumin (HSA) variants with increased affinity for human FcRn at
      endosomal pH, enabling us to solve the crystal structure of a variant HSA/FcRn
      complex. We find an extensive, primarily hydrophobic interface stabilized by
      hydrogen-bonding networks involving protonated histidines internal to each
      protein. The interface features two key FcRn tryptophan side chains inserting
      into deep hydrophobic pockets on HSA that overlap albumin ligand binding sites.
      We find that fatty acids (FAs) compete with FcRn, revealing a clash between
      ligand binding and recycling, and that our high-affinity HSA variants have
      significantly increased circulating half-lives in mice and monkeys. These
      observations open the way for the creation of biotherapeutics with significantly
      improved pharmacokinetics. 

PMID- 24120762
TI  - Complex energy landscape of a giant repeat protein.
AB  - Here, we reveal a remarkable complexity in the unfolding of giant HEAT-repeat
      protein PR65/A, a molecular adaptor for the heterotrimeric PP2A phosphatases. The
      repeat array ruptures at multiple sites, leading to intermediate states with
      noncontiguous folded subdomains. There is a dominant sequence of unfolding, which
      reflects a nonuniform stability distribution across the repeat array and can be
      rationalized by theoretical models accounting for heterogeneous contact density
      in the folded structure. Unfolding of certain intermediates is, however,
      competitive, leading to parallel unfolding pathways. The low-stability, central
      repeats sample unfolded conformations under physiological conditions, suggesting
      how folding directs function: certain regions present rigid motifs for molecular
      recognition, whereas others have the flexibility with which to broaden the search
      area, as in the fly-casting mechanism. Partial unfolding of PR65/A also impacts
      catalysis by altering the proximity of bound catalytic subunit and substrate.
      Thus, the repeat array orchestrates the assembly and activity of PP2A. 

PMID- 24120763
TI  - Structure of FGFR3 transmembrane domain dimer: implications for signaling and
      human pathologies.
AB  - Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via
      lateral dimerization in the plasma membrane, and plays an important role in human
      development and disease. Eight different pathogenic mutations, implicated in
      cancers and growth disorders, have been identified in the FGFR3 transmembrane
      segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in
      membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two
      transmembrane helices pack into a symmetric left-handed dimer, with
      intermolecular stacking interactions occurring in the dimer central region. Some
      pathogenic mutations fall within the helix-helix interface, whereas others are
      located within a putative alternative interface. This implies that although the
      observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3
      mediated transduction across the membrane is complex. We propose an FGFR3
      signaling mechanism that is based on the solved structure, available structures
      of isolated soluble FGFR domains, and published biochemical and biophysical data.

PMID- 24120765
TI  - Schizophrenia-like disruptions of sensory gating by serotonin receptor
      stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT.
AB  - Schizophrenia pathophysiology is associated with alterations in several
      neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT).
      Schizophrenia patients also have disruptions in sensory gating, a brain
      information filtering mechanism in response to repeated sensory stimuli. Dopamine
      and glutamate have been implicated in sensory gating; however, little is known
      about the contribution of serotonin. We therefore investigated the effects of
      several psychoactive compounds that alter serotonergic neuronal activity on event
      related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were
      implanted with cortical surface electrodes to measure ERPs to 150 presentations
      of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated
      animals suppressed the response to S2 to less than 50% of S1. In contrast,
      treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C
      receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT
      (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components
      suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on
      the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to
      S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These
      results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats.
      These results may help to elucidate the sensory gating deficits observed in
      schizophrenia patients.

PMID- 24120764
TI  - Cofactor molecules induce structural transformation during infectious prion
      formation.
AB  - The spread of misfolded proteins may occur in many neurodegenerative diseases.
      Mammalian prions are currently the only misfolded proteins in which high specific
      biological infectivity can be produced in vitro. Using a system that generates
      infectious prions de novo from purified recombinant PrP and conversion cofactors
      palmitoyl-oleoyl-phosphatidylglycerol (POPG) and RNA, we examined by deuterium
      exchange mass spectrometry (DXMS) the stepwise protein conformational changes
      that occur during prion formation. We found that initial incubation with POPG
      causes major structural changes in PrP involving all three alpha helices and one
      beta strand, with subsequent addition of RNA rendering the N terminus highly
      exposed. Final conversion into the infectious PrP(Sc) form was accompanied by
      globally decreased solvent exposure, with persistence of the major cofactor
      induced conformational features. Thus, we report that cofactor molecules appear
      to induce major structural rearrangements during prion formation, initiating a
      dynamic sequence of conformational changes resulting in biologically active
      prions. 

PMID- 24120766
TI  - P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5
      HT1A receptors.
AB  - It has been described that endogenous ATP via activation of P2X3 and P2X2/3
      receptors contributes to inflammatory nociception in different models, including
      the formalin injected in subcutaneous tissue of the rat's hind paw. In this
      study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors, whose
      activation is essential to formalin-induced inflammatory nociception, are
      involved in the nociception induced by activation of P2X3 receptors on
      subcutaneous tissue of the rat's hind paw. We have also evaluated whether the
      activation of P2X3 receptors increases the susceptibility of primary afferent
      neurons to formalin action modulated by activation of TRPA1, 5-HT3 or 5-HT1A
      receptors. Nociceptive response intensity was measured by observing the rat's
      behavior and considering the number of times the animal reflexively raised its
      hind paw (flinches) in 60min. Local subcutaneous administration of the selective
      TRPA1, 5-HT3 or 5-HT1A receptor antagonists HC 030031, tropisetron and WAY
      100,135, respectively, prevented the nociceptive responses induced by the
      administration in the same site of the non-selective P2X3 receptor agonist
      alphabetameATP. Administration of the selective P2X3 and P2X2/3 receptor
      antagonist A-317491 or pretreatment with oligonucleotides antisense against P2X3
      receptor prevented the formalin-induced behavioral nociceptive responses during
      the first and second phases. Also, the co-administration of a subthreshold dose
      of alphabetameATP with a subthreshold dose of formalin induced nociceptive
      behavior, which was prevented by local administration of tropisetron, HC 030031
      or WAY 100, 135. These findings have demonstrated that the activation of P2X3
      receptors induces inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A
      receptors. Also, they suggest that inflammatory nociception is modulated by the
      release of endogenous ATP and P2X3 receptor activation, which in turn, increases
      primary afferent nociceptor susceptibility to the action of inflammatory
      mediators via interaction with TRPA1, 5-HT3 and 5-HT1A receptors in the
      peripheral tissue. 

PMID- 24120767
TI  - Intermittent swim stress causes Morris water maze performance deficits in a
      massed-learning trial procedure that are exacerbated by reboxetine.
AB  - Various animal models of depression have been used to seek a greater
      understanding of stress-related disorders. However, there is still a great need
      for research in this area, as many unanswered questions remain. Therefore, we
      sought to employ a novel animal model of depression known as intermittent swim
      stress (ISS). In this model, the animal experiences 100 trials of cold water swim
      stress. ISS has already shown subsequent immobility in the forced swim test
      (FST), deficits in instrumental and spatial (spaced-trial procedure), and
      responsiveness to norepinephrine. We are now examining how this will translate in
      the Morris water maze for rats in a massed-learning trial procedure, and further
      assessing ISS sensitivity toward norepinephrine selective anti-depressant drugs.
      The results indicated no difference in cued learning when the platform was
      visible in the water maze, but a hidden platform task revealed poorer spatial
      learning for ISS-exposed rats versus controls. In terms of spatial memory, there
      was a notable ISS-induced deficit 1h after the learning trials, regardless of
      performance on the previous platform task. Interestingly, the administration of
      reboxetine interfered with the spatial learning and memory trials for both ISS
      and CC groups. As a result, ISS exposure compromised spatial learning and memory
      in the Morris water maze, and norepinephrine does not appear to be a mediator of
      this deficit. The results demonstrate a key difference in the effects of
      reboxetine in a massed- vs. spaced-learning trial procedure in the Morris water
      maze following ISS exposure. 

PMID- 24120769
TI  - Re: Illness uncertainty and quality of life of patients with small renal tumors
      undergoing watchful waiting: a 2-year prospective study.

PMID- 24120768
TI  - Motor cortex stimulation for ALS: open label extension study of a previous small
      trial.

PMID- 24120770
TI  - Re: Significant variability in 10-year cumulative radiation exposure incurred on
      different surveillance regimens after surgery for pT1 renal cancers: yet another
      reason to standardize protocols?

PMID- 24120771
TI  - Re: Image-guided percutaneous renal cryoablation: preoperative risk factors for
      recurrence and complications.

PMID- 24120772
TI  - Re: The role of R.E.N.A.L. nephrometry score in the era of robot-assisted partial
      nephrectomy.

PMID- 24120774
TI  - Re: Optical spectroscopy techniques can accurately distinguish benign and
      malignant renal tumours.

PMID- 24120775
TI  - Re: Contrast-enhanced magnetic resonance urography at 3T: clinical feasibility.

PMID- 24120776
TI  - Re: Combination of molecular alterations and smoking intensity predicts bladder
      cancer outcome: a report from the Los Angeles Cancer Surveillance Program.

PMID- 24120777
TI  - Re: The burden of urinary incontinence and urinary bother among elderly prostate
      cancer survivors.

PMID- 24120778
TI  - Re: Prostate HistoScanning: a screening tool for prostate cancer?

PMID- 24120779
TI  - Re: Long-term functional outcomes after treatment for localized prostate cancer.

PMID- 24120780
TI  - Re: Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a
      baseline analysis in the Canary Prostate Active Surveillance Study.

PMID- 24120781
TI  - Re: Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive
      and transrectal US-MR fusion guidance versus systematic biopsy--prospective
      multicenter study.

PMID- 24120782
TI  - Re: Effect of age, tumor risk, and comorbidity on competing risks for survival in
      a u.s. Population-based cohort of men with prostate cancer.

PMID- 24120783
TI  - Re: Prostate specific antigen testing policy worldwide varies greatly and seems
      not to be in accordance with guidelines: a systematic review.

PMID- 24120784
TI  - Re: Anti-tumour activity of two novel compounds in cisplatin-resistant testicular
      germ cell cancer.

PMID- 24120785
TI  - Re: Prevalence of the metabolic syndrome and cardiovascular disease risk in
      chemotherapy-treated testicular germ cell tumour survivors.

PMID- 24120786
TI  - Re: Outpatient urological procedures in antibiotic-naive patients with bladder
      cancer with asymptomatic bacteriuria.

PMID- 24120787
TI  - Re: Impact of pH on activity of trimethoprim, fosfomycin, amikacin, colistin and
      ertapenem in human urine.

PMID- 24120788
TI  - Re: Flexible cystoscopy findings in patients investigated for profound lower
      urinary tract symptoms, recurrent urinary tract infection, and pain.

PMID- 24120789
TI  - Re: Differences in 24-hour urine composition between apatite and brushite stone
      formers.

PMID- 24120790
TI  - Re: Phenotypic characterization of kidney stone formers by endoscopic and
      histological quantification of intrarenal calcification.

PMID- 24120791
TI  - Re: Long-term outcome of the use of intravesical botulinum toxin for the
      treatment of overactive bladder (OAB).

PMID- 24120792
TI  - Re: Anticholinergic drugs for adult neurogenic detrusor overactivity: a
      systematic review and meta-analysis.

PMID- 24120793
TI  - Re: Prevalence and risk factors for nocturia in middle-aged and elderly people
      from public health centers in Taiwan.

PMID- 24120794
TI  - Re: The prevalence and natural history of urinary symptoms among recreational
      ketamine users.

PMID- 24120795
TI  - Re: Association between nocturia and falls-related long-term mortality risk in
      the elderly.

PMID- 24120796
TI  - Re: The impact of organizational factors on the urinary incontinence care quality
      in long-term care hospitals: a longitudinal correlational study.

PMID- 24120797
TI  - Re: Constitutional, organopathic and combined homeopathic treatment of benign
      prostatic hypertrophy: a clinical trial.

PMID- 24120798
TI  - Re: Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in
      benign prostatic hyperplasia: systematic review and meta-analysis of randomized
      controlled trials.

PMID- 24120800
TI  - Re: Prevalence of sexual dysfunctions among women with multiple sclerosis.

PMID- 24120803
TI  - Re: Effect of testosterone administration on liver fat in older men with mobility
      limitation: results from a randomized controlled trial.

PMID- 24120804
TI  - Re: Sexual activity and function in women more than 2 years after midurethral
      sling placement.

PMID- 24120805
TI  - Re: Association between body size and composition and erectile dysfunction in
      older men: osteoporotic fractures in men study.

PMID- 24120806
TI  - Re: Mystery of idiopathic male infertility: is oxidative stress an actual risk?

PMID- 24120807
TI  - Re: Association of exposure to phenols and idiopathic male infertility.

PMID- 24120808
TI  - Re: Seminal and molecular evidence that sauna exposure affects human
      spermatogenesis.

PMID- 24120809
TI  - Re: Effect of an isotonic lubricant on sperm collection and sperm quality.

PMID- 24120810
TI  - Re: Association of state and trait anxiety to semen quality of in vitro
      fertilization patients: a controlled study.

PMID- 24120811
TI  - Re: Unilateral multicystic dysplastic kidney: does initial size matter?

PMID- 24120812
TI  - Re: Hypertension in pediatric patients with renal scarring in association with
      vesicoureteral reflux.

PMID- 24120813
TI  - Re: Distal ureteral diameter measurement objectively predicts vesicoureteral
      reflux outcome.

PMID- 24120815
TI  - Re: PRC1 coordinates timing of sexual differentiation of female primordial germ
      cells.

PMID- 24120816
TI  - Re: Aire-dependent thymic development of tumor-associated regulatory T cells.

PMID- 24120817
TI  - Re: The passive and active contractile properties of the neurogenic, underactive
      bladder.

PMID- 24120818
TI  - Re: Shrinkage of experimental benign prostatic hyperplasia and reduction of
      prostatic cell volume by a gastrin-releasing Peptide antagonist.

PMID- 24120820
TI  - In vitro safety cardiovascular pharmacology studies: impact of formulation
      preparation and analysis.
AB  - Collection of formulation samples is required for GLP in vitro studies to check
      the exposure of the test system and allow reliable determinations of safety
      margins. In vitro studies conducted in-house were investigated to evaluate
      problems of solubility, stability and adsorption of the formulations. Terfenadine
      was used as reference substance to illustrate the purpose. Lowered target
      concentrations of test substances in in vitro studies can be attributed to the
      solubility limitation in the superfusion medium, the low stability under frozen
      conditions (24% of the final solutions stable at -20  degrees C) and/or the
      adsorption on the superfusion tubing (30% of the studies). Terfenadine also
      showed a limited solubility (measured concentrations ranging from 0.597 MUM to
      0.833 MUM instead of 1 MUM) and a loss of substance through the superfusion
      tubing from -30.2% to -39.2% with dimethylsulfoxide, ethanol or methanol.
      Terfenadine solubility was improved with 2-hydroxypropyl-beta-cyclodextrin, no
      adsorption was observed, but its capacity to block the hERG channel was
      decreased. It is recommended to determine the substance solubility in appropriate
      buffers, to evaluate possible adsorption during method validation (formulation
      samples collected after superfusion), and to prepare fresh formulation each
      testing day with immediate analysis in absence of stability data. This strategy
      clearly favors single-site as opposed to multi-site studies.

PMID- 24120821
TI  - Apolipoprotein C-II is a potential serum biomarker as a prognostic factor of
      locally advanced cervical cancer after chemoradiation therapy.
AB  - PURPOSE: To determine pretreatment serum protein levels for generally applicable
      measurement to predict chemoradiation treatment outcomes in patients with locally
      advanced squamous cell cervical carcinoma (CC). METHODS AND MATERIALS: In a
      screening study, measurements were conducted twice. At first, 6 serum samples
      from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused
      death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from
      different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined.
      Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were
      analyzed in the validation study. Protein chips were treated with the sample
      sera, and the serum protein pattern was detected by surface-enhanced laser
      desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Then,
      single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based
      peptide/protein identification methods, were used to identify protein
      corresponding to the detected peak. And then, turbidimetric assay was used to
      measure the levels of a protein that indicated the best match with this peptide
      peak. RESULTS: The same peak 8918 m/z was identified in both screening studies.
      Neither the screening study nor the validation study had significant differences
      in the appearance of this peak in the controls and NED. However, the intensity of
      the peak in CD was significantly lower than that of controls and NED in both
      pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein
      indicated the best match with this peptide peak at 8918 m/z was identified as
      apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay
      showed that the mean serum levels of ApoC-II tended to decrease in CD group when
      compared with NED group (P=.078). CONCLUSION: ApoC-II could be used as a
      biomarker for detection in predicting and estimating the radiation treatment
      outcome of patients with CC.

PMID- 24120822
TI  - High-dose and extended-field intensity modulated radiation therapy for early
      stage NK/T-cell lymphoma of Waldeyer's ring: dosimetric analysis and clinical
      outcome.
AB  - PURPOSE: To assess the dosimetric benefit, treatment outcome, and toxicity of
      high-dose and extended-field intensity modulated radiation therapy (IMRT) in
      patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL).
      METHODS AND MATERIALS: Thirty patients with early-stage WR-NKTCL who received
      extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy
      to the primary involved regions and positive cervical lymph nodes (planning
      target volume requiring radical irradiation [PTV50]) and 40 Gy to the negative
      cervical nodes (PTV40). Dosimetric parameters for the target volume and critical
      normal structures were evaluated. Locoregional control (LRC), overall survival
      (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier
      method. RESULTS: The median mean doses to the PTV50 and PTV40 were 53.2 Gy and
      43.0 Gy, respectively. Only 1.4% of the PTV50 and 0.9% of the PTV40 received less
      than 95% of the prescribed dose, indicating excellent target coverage. The
      average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy,
      respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%.
      Most acute toxicities were grade 1 to 2, except for grade >=3 dysphagia and
      mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient
      developed any >=grade 3 late toxicities. A correlation between the mean dose to
      the parotid glands and the degree of late xerostomia was observed. CONCLUSIONS:
      IMRT achieves excellent target coverage and dose conformity, as well as favorable
      survival and locoregional control rates with acceptable toxicities in patients
      with WR-NKTCL.

PMID- 24120823
TI  - Effect of field size and length of plantar spur on treatment outcome in radiation
      therapy of plantar fasciitis: the bigger the better?
AB  - PURPOSE: Radiation therapy is well established in the treatment of painful
      plantar fasciitis or heel spur. A retrospective analysis was conducted to
      investigate the effect of field definition on treatment outcome and to determine
      the impact of factors potentially involved. METHODS AND MATERIALS: A review of
      treatment data of 250 patients (285 heels) with a mean follow-up time of 11
      months showed that complete symptom remission occurred in 38%, partial remission
      in 32%, and no change in 19% (11% were lost to follow-up). Variables such as
      radiologic evidence of plantar spurs, their length, radiation dose, field size,
      age, sex, and onset of pain before administration of radiation therapy were
      investigated in univariate and multivariate regression analyses. RESULTS:
      Treatment response depended upon age >53 years, length of heel spur <=6.5 mm (or
      no radiologic evidence of a heel spur), and onset of pain <12 months before
      radiation therapy. Patients with these clinical prerequisites stood a 93% chance
      of clinical response. Without these prerequisites, only 49% showed any impact. No
      influence of field size on treatment outcome became evident. CONCLUSION: Patients
      with short plantar heel spurs benefit from radiation therapy equally well as
      patients without any radiologic evidence. Moreover, smaller field sizes have the
      same positive effect as commonly used large field definitions covering the entire
      calcaneal bone. This leads to a recommendation of a considerable reduction of
      field size in future clinical practice.

PMID- 24120824
TI  - Changes in gait kinematics and lower back muscle activity post-radiofrequency
      denervation of the zygapophysial joint: a case study.
AB  - BACKGROUND CONTEXT: Using diagnostic anesthetic blocks, the lumbar zygapophysial
      (facet) joint has been shown to be the primary cause of pain in approximately 15%
      of patients with chronic low back pain. Radiofrequency neurotomy (RFN) of the
      lumbar medial branch innervating the zygapophysial joint has been shown to
      provide a significant decrease in pain in patients selected by dual comparative
      anesthetic blocks, but quantitative improvements in mobility have not been fully
      elucidated. A theoretical concern with RFN is that the multifidus muscle, a
      stabilizing paraspinal muscle, is also denervated during this procedure, which
      may have adverse effects on mobility and spine stability. PURPOSE: The purpose of
      this study was to examine gait kinematics and muscle activity of the low back
      during treadmill walking both before and after RFN. STUDY DESIGN: Case study.
      PATIENT SAMPLE: One 33-year-old female, with 15 years of chronic left low back
      pain and a diagnosis of L4/L5 lumbar zygapophysial joint pain by dual comparative
      anesthetic blocks was studied. OUTCOME MEASURES: Self-reported measures of
      perceived pain and effort; in addition to physiologic measures of heart rate,
      gait kinematics and surface electromyography (EMG) activity of the multifidus and
      erector spinae muscles were collected before and after the procedure. METHODS:
      The participant walked for 15 consecutive minutes on a treadmill. The first and
      last 5-minute intervals were at a self-selected pace, and the middle 5-minute
      interval was at a 50% increase of the self-selected pace. Gait kinematics and
      lumbar paraspinal surface EMG activity were recorded during the last minute of
      each walking interval. Heart rate, perceived effort, and perceived pain were also
      collected at the end of each walking interval. Data were collected both 7 and 1
      days before RFN, and on the following days post-RFN: 0, 8, 14, 28, and 58.
      RESULTS: Perceived effort did not change despite an increase in treadmill speed
      and heart rate. Pain decreased by 60% in the first two weeks and by 92% by 4
      weeks post-RFN. There were also gradual positive changes in gait kinematics
      across all post-sessions and an immediate and sustained decrease in surface EMG
      activity over the left multifidus and erector spinae muscles following RFN.
      CONCLUSIONS: The results of this pilot study are the first to show quantitative
      positive changes in gait and muscle activity post-RFN, suggesting that the
      relationship between this procedure and mobility warrant further investigation.

PMID- 24120825
TI  - The prevalence of abnormal preoperative coagulation tests in pediatric patients
      undergoing spinal surgery for scoliosis.
AB  - BACKGROUND CONTEXT: Multilevel spinal fusion surgery for deformity correcting
      spinal surgery in pediatric patients with scoliosis has typically been associated
      with significant blood loss. The mechanism of bleeding in such patients is not
      fully understood. Coagulation abnormalities, which may be associated with
      scoliosis, are thought to play a role. PURPOSE: To document and compare the
      prevalence of preoperative coagulation abnormalities among patients with
      scoliosis attending a pediatric orthopedic department for spinal fusion surgery
      with patients attending for minor surgery. STUDY DESIGN: An observational study.
      All patients were recruited from a pediatric tertiary referral center in Dublin,
      Ireland. PATIENT SAMPLE: Coagulation profile results were prospectively collected
      over a 2-year period from 165 spinal surgery patients. In total, 175 patients
      were included in the non-scoliosis group. These patients attended the day ward
      for minor procedures and were recruited over a 4-month period. OUTCOME MEASURES:
      The primary outcome measure was the coagulation profiles, which included
      prothrombin time, activated partial thromboplastin time (APTT), and thrombin time
      (TT). Levels of Coagulation Factors II, V, VII, and X were also recorded.
      METHODS: All blood samples were sent to the haematology laboratory to establish
      the coagulation profile. The primary outcome was the presence of an abnormal
      coagulation screening test (if any of PT, APTT, or TT were abnormal). Prothrombin
      time, APTT, and TT were also analyzed as individual continuous variables, as well
      as Coagulation Factors II, V, VII, and X. Regression analysis was used to compare
      the coagulation profile of scoliosis patients with that of non-scoliosis
      patients. There were no outside funding sources or any potential conflict of
      interest associated with this study. RESULTS: The scoliosis patients were more
      likely to have an abnormal preoperative screening test compared with non
      scoliosis patients, with an odds ratio of 2.6. Further analysis showed
      statistically significant longer clotting times for patients with scoliosis
      compared with those without; PT (t=3.37, p=.001), APTT (t=4.26, p<.001), TT
      (t=4.52, p<.001). Of the coagulation factors analyzed, only factor X was
      significantly different in scoliosis patients compared with non-scoliosis
      controls (t=-4.41, p<.001). CONCLUSIONS: Children with scoliosis have a higher
      prevalence of preoperative coagulation abnormalities compared with normal healthy
      patients.

PMID- 24120827
TI  - Intestinal microsporidiosis in a reference center.

PMID- 24120826
TI  - Interleukin-12 gene adjuvant increases the immunogenicity of virus-like particles
      of human papillomavirus type 16 regional variant strain.
AB  - OBJECTIVES: To analyze the immunogenicity of virus-like particles (VLP) of human
      papillomavirus type 16 (HPV16) isolated in East China and the adjuvant potential
      of interleukin-12 (IL-12). METHODS: The variant HPV16 L1VLP expressed in sf9
      insect cells were purified with cesium chloride gradient centrifugation. BALB/c
      mice were vaccinated with VLP (L1N), VLP with Freund's adjuvant (L1A) or VLP with
      IL-12 recombinant plasmid (L1P). HPV16 VLP specific IgG and IFN-gamma level in
      the serum were detected by ELISA, and the percentage of CD4(+) and CD8(+) in
      spleen cells was detected with flow cytometry. RESULTS: The titers of serum IgG
      antibodies in vaccinated groups were higher than in negative control and the
      serum antibodies mainly recognized conformation-dependent HPV16 VLP epitopes.
      Splenic CD4(+) and CD8(+) T cell subsets increased after vaccination in every
      experimental group, and CD8(+) increased obviously in L1P group. The ratio of
      CD4(+)/CD8(+) decreased in L1P group and increased in the other two groups,
      compared to control group. Vaccination induced specific secretion of IFN-gamma in
      the serum of vaccinated group (p<0.05), especially in the L1P group. CONCLUSIONS:
      VLP of HPV16 variant strain isolated in East China could induce humoral immunity
      and cellular immunity in mice, and IL-12 recombinant plasmid can enhance cellular
      immunity.

PMID- 24120828
TI  - Paracoccidioidomycosis: evaluation of treatment and patient profile.

PMID- 24120829
TI  - Epidemiologic profile of Streptococcus agalactiae colonization in pregnant women
      attending prenatal care in a city of southern of Brazil.

PMID- 24120830
TI  - Pantoea dispersa: an unusual cause of neonatal sepsis.
AB  - Neonatal septicemia is the most important cause of neonatal mortality. A wide
      variety of bacteria both aerobic and anaerobic can cause neonatal sepsis. Genus
      Pantoea is a member of Enterobacteriaceae family that inhabits plants, soil and
      water and rarely causes human infections, however, Pantoea dispersa has not been
      reported as a causative organism for neonatal sepsis. We hereby report two
      neonates with early onset sepsis caused by Pantoea dispersa. Early detection and
      appropriate antibiotic therapy can improve overall outcome of this rare infection
      in neonates. 

PMID- 24120831
TI  - Bacteremic pneumococcal pneumonia: serotype distribution, antimicrobial
      susceptibility, severity scores, risk factors, and mortality in a single center
      in Chile.
AB  - AIMS: Bacteremic pneumococcal pneumonia (BPP) is a severe condition. To evaluate
      seasonal distribution, mortality, serotype frequencies, antimicrobial
      susceptibility, and different severity scores among patients with BPP. PATIENTS
      AND METHODS: Patients were identified by laboratory data and restricted to
      adulthood. Standard methods were used for serotyping and antimicrobial
      susceptibility. Risk factors were analyzed by univariate and multivariate
      methods. Severity scores (APACHE II, CURB-65 and CAP PIRO) were compared using
      ROC curves. RESULTS: Sixty events of community-acquired BPP occurred between 2005
      and 2010. A seasonal pattern was detected. Mean age was 72.1 years old (81.4% >=
      60 years). All had a predisposing factor. Previous influenza (3.3%) or
      pneumococcal immunization (1.7%) was infrequent. Admission to critical units was
      required by 51.7%. Twenty-two serotypes were identified among 59 strains. Only
      one strain had intermediate resistance to penicillin (1.7%). In-hospital
      mortality reached 33.3%. Multivariate analysis identified a CAP PIRO score>3 (OR
      29.7; IC95 4.7-187), age >= 65 years (OR 42.1; IC95 2.2-796), and a platelet
      count<100,000/MUL (OR 10.9; IC95 1.2-96) as significant independent factors
      associated with death. ROC curve analysis did not reveal statistical differences
      between the three severity scores to predict death (AUC 0.77-0.90). The
      prognostic yield for all of them was limited (Positive Likelihood Ratio: 1.5
      3.8). CONCLUSIONS: BPP had a high case-fatality rate in this group of adult
      patients with no association to resistant isolates, and a low immunization
      record. Three independent factors were related to death and the prognostic yield
      of different severity scores was low.

PMID- 24120832
TI  - Value of real-time polymerase chain reaction in bronchoalveolar lavage fluid for
      diagnosis of pediatric pulmonary tuberculosis.

PMID- 24120833
TI  - Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon
      and ribavirin treatment for chronic hepatitis C: case report and literature
      review.
AB  - Pegylated interferon alpha (Peg IFN-alpha) in combination with ribavirin is the
      backbone of treatment in chronic hepatitis C (CHC). Cardiotoxicity due to
      interferon therapy is rare. The most frequent cardiovascular complications are
      arrhythmias and ischemic manifestations. Cardiomyopathy is extremely rare but can
      be life threatening. We present the case of a 41-year-old female patient with CHC
      in whom Peg IFN-alpha induced dilated cardiomyopathy and hypothyroidism. Chest
      radiography showed an enlarged and globular cardiac silhouette and pulmonary
      congestion. Echocardiography showed decreased left ventricular systolic function
      with an ejection fraction of 32% and fractional shortening of 15%. Cardiomyopathy
      had a complete remission after cessation of antiviral therapy with short-term
      heart failure medications and supportive care. Then we review the current
      literature about interferon induced cardiomyopathy in patients with HCV
      infection, as well as share our clinical experience in diagnosing and managing
      this rare complication. 

PMID- 24120834
TI  - Susceptibility rates in Latin American nations: report from a regional resistance
      surveillance program (2011).
AB  - OBJECTIVE: To establish a resistance (R) surveillance program monitoring
      antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG],
      Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA],
      Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). METHODS: In 2011, 4979
      organisms were collected from 11 nations (20 laboratories) for susceptibility
      testing in a central laboratory design. Antimicrobials were tested by CLSI
      methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram
      positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299],
      enterococci [218], Streptococcus pneumoniae [SPN; 182], beta-haemolytic
      streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP;
      517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters
      [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN),
      tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin
      (AMK). RESULTS: MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD
      (MIC90, 2mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains.
      Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG
      and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr).
      Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%,
      respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were
      observed in EC (54-71%) and KSP (>=50%) from GUA, MEX and Peru, and six nations,
      respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in
      BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and
      carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae.
      Only COL inhibited >90% of PSA; COL and TIG (<=2mg/L) covered >=85% of ACB.
      CONCLUSIONS: LATAM nations demonstrated variable levels of antimicrobial R
      especially among Enterobacteriaceae (beta-lactamase-mediated), PSA and ACB. MRSA
      (48%), VRE (14%) and multidrug-R SPN were also regional therapeutic challenges.

PMID- 24120835
TI  - The importance of the last strand at the C-terminus in betaB2-crystallin
      stability and assembly.
AB  - Congenital cataract is the leading cause of childhood blindness worldwide.
      Investigations of the effects of inherited mutations on protein structure and
      function not only help us to understand the molecular mechanisms underlying
      congenital hereditary cataract, but also facilitate the study of complicated
      cataract and non-lens abnormities caused by lens-specific genes. In this
      research, we studied the effects of the V187M, V187E and R188H mutations on
      betaB2-crystallin structure and stability using a combination of biophysical,
      cellular and molecular dynamic simulation analysis. Both V187 and R188 are
      located at the last strand of betaB2-crystallin Greek-key motif 4. All of the
      three mutations promoted betaB2-crystallin aggregation in vitro and at the
      cellular level. These three mutations affected betaB2-crystallin quite
      differentially: V187M influenced the hydrophobic core of the C-terminal domain,
      V187E was a Greek-key motif breaker with the disruption of the backbone H-bonding
      network, while R188H perturbed the dynamic oligomeric equilibrium by dissociating
      the dimer and stabilizing the tetramer. Our results highlighted the importance of
      the last strand in the structural integrity, folding, assembly and stability of
      beta-crystallins. More importantly, we proposed that the perturbation of the
      dynamic equilibrium between beta-crystallin oligomers was an important mechanism
      of congenital hereditary cataract. The selective stabilization of one specific
      high-order oligomer by mutations might also be deleterious to the stability and
      folding of the beta-crystalllin homomers and heteromers. The long-term structural
      stability and functional maintenance of beta-crystallins are achieved by the
      precisely regulated oligomeric equilibrium. 

PMID- 24120837
TI  - Functional heterogeneity of pulmonary surfactant protein-D in cystic fibrosis.
AB  - Pulmonary surfactant protein-D (SP-D) is a soluble collagenous C-type lectin with
      important anti-microbial and anti-inflammatory properties. Although it is subject
      to functionally relevant modification by common polymorphisms and unregulated
      inflammation, the functional status of SP-D in cystic fibrosis (CF) remains
      unclear. Given the importance of infection and inflammation in CF lung pathology
      we have undertaken the first systematic analysis of SP-D lectin activity in this
      population. By ELISA, we found that airway lavage fluid SP-D expression was
      greater in CF compared to control patients but was reduced in CF patients with
      infection and correlated negatively with markers of neutrophilic inflammation. In
      a functional assay, the percentage of SP-D capable of binding zymosan rarely
      exceeded 60% in CF or control patients and similarly restricted binding activity
      was observed towards maltose-agarose. SP-D lectin activity also correlated
      negatively with infection and neutrophilic inflammation but there was little
      evidence of major proteolytic degradation amongst the non-bound material. SP-D
      which failed to bind zymosan exhibited features of lower oligomeric form compared
      to bound material when tested by native gel electrophoresis. Furthermore, when
      separated by gel chromatography, high and low oligomeric populations of SP-D were
      observed in CF lavage fluid but only high oligomeric forms exhibited substantial
      lectin activity towards yeast derived mannan. Our data demonstrate that
      oligomeric heterogeneity underlies functional diversity amongst SP-D in health
      and disease and that dynamic regulation of oligomerisation is an important
      feature of SP-D biology. 

PMID- 24120836
TI  - Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics
      studies.
AB  - The initiation and progression of Alzheimer disease (AD) is a complex process not
      yet fully understood. While many hypotheses have been provided as to the cause of
      the disease, the exact mechanisms remain elusive and difficult to verify.
      Proteomic applications in disease models of AD have provided valuable insights
      into the molecular basis of this disorder, demonstrating that on a protein level,
      disease progression impacts numerous cellular processes such as energy
      production, cellular structure, signal transduction, synaptic function,
      mitochondrial function, cell cycle progression, and proteasome function. Each of
      these cellular functions contributes to the overall health of the cell, and the
      dysregulation of one or more could contribute to the pathology and clinical
      presentation in AD. In this review, foci reside primarily on the amyloid beta
      peptide (Abeta) induced oxidative stress hypothesis and the proteomic studies
      that have been conducted by our laboratory and others that contribute to the
      overall understanding of this devastating neurodegenerative disease.

PMID- 24120838
TI  - Sex differences in effects of dopamine D1 receptors on social withdrawal.
AB  - Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the
      regulation of motivational states. Recent studies in male rodents show that
      social defeat stress increases the activity of ventral tegmental dopamine neurons
      projecting to the NAc, and that this increased activity is necessary for stress
      induced social withdrawal. Domestic female mice are not similarly aggressive,
      which has hindered complementary studies in females. Using the monogamous
      California mouse (Peromyscus californicus), we found that social defeat increased
      total dopamine, DOPAC, and HVA content in the NAc in both males and females.
      These results are generally consistent with previous studies in Mus, and suggest
      defeat stress also increases NAc dopamine signaling in females. However, these
      results do not explain our previous observations that defeat stress induces
      social withdrawal in female but not male California mice. Pharmacological
      manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was
      infused in the NAc shell of females that were naive to defeat, social interaction
      behavior was reduced. This same dose of SKF38393 had no effect in males,
      suggesting that D1 receptor activation is sufficient to induce social withdrawal
      in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390
      increased social approach behavior in females exposed to defeat but not in
      females naive to defeat. This result suggests that D1 receptors are necessary for
      defeat-induced social withdrawal. Overall, our results suggest that sex
      differences in molecular pathways that are regulated by D1 receptors contribute
      to sex differences in social withdrawal behavior.

PMID- 24120839
TI  - Assessment of the psychometric properties of the Spanish language version of
      questionnaire ICIQ-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS).
AB  - OBJECTIVES: To evaluate the psychometric properties of the Spanish version of the
      ICIQ-Male Lower Urinary Tract Symptoms Questionnaire (ICIQ-MLUTS): Feasibility (%
      of completion and ceiling/ground effects), reliability (Test-retest), convergent
      validity (vs Bladder Control Self-Assessment Questionnaire [BSAQ] and vs
      International Prostate Symptom Score [I-PSS]) and criterion validity (according
      to presence or absence of symptoms). MATERIAL AND METHODS: This was an
      observational, non-interventionist and multicenter study. 223 male patients with
      lower urinary tract symptoms (LUTS), predominantly storage symptoms and aged 18
      65, took part in the study. Patients completed the ICIQ-MLUTS (test), I-PSS and
      BSAQ questionnaires and referred their urinary symptoms in a single visit, with
      the exception of a subgroup composed by 49 patients that completed the
      questionnaire again 15 days after initial visit to evaluate test-retest
      reliability. The questionnaire includes 13 items divided in 2 sub-scales: Voiding
      symptoms (V) from 0-20 and Incontinence symptoms (I) from 0-24. RESULTS:
      Percentage of patients that completed all items: 98.84%. Ground effect is 0 and
      ceiling effect was under 6% in both sub-scales. Test-retest reliability:
      Intraclass correlation coefficient (ICC) ranged from 0.68 to 0.88, except on
      Delay. Kappa shows a good agreement, between 0.60 and 0.81, except for Nocturia.
      Convergent validity: Correlation (Spearman) between the questionnaire sub-scales
      scores and the rest of measures is statistically significant (P < .01 and P <
      .05). Criterion validity: Statistically significant differences (P < .05) between
      scores on ICIQ-MLUTS, from patients that refer experiencing symptoms and those
      who do not. CONCLUSION: The Spanish version of the ICIQ-MLUTS questionnaire shows
      adequate feasibility, reliability and validity.

PMID- 24120840
TI  - The epidemiology of microscopic colitis in Olmsted County from 2002 to 2010: a
      population-based study.
AB  - BACKGROUND & AIMS: The increasing incidence of microscopic colitis has been
      partly attributed to detection bias. We aimed to ascertain recent incidence
      trends and the overall prevalence of microscopic colitis in a population-based
      study. METHODS: Using data from the Rochester Epidemiology Project, we identified
      residents of Olmsted County, Minnesota, who were diagnosed with collagenous
      colitis or lymphocytic colitis from January 1, 2002, through December 31, 2010,
      based on biopsy results and the presence of diarrhea (N = 182; mean age at
      diagnosis, 65.8 years; 76.4% women). Poisson regression analyses were performed
      to evaluate associations between incidence and age, sex, and calendar period.
      RESULTS: The age- and sex-adjusted incidence of microscopic colitis was 21.0
      cases per 100,000 person-years (95% confidence interval [CI], 18.0-24.1 cases per
      100,000 person-years). The incidence of lymphocytic colitis was 12.0 per 100,000
      person-years (95% CI, 9.6-14.3 per 100,000 person-years) and collagenous colitis
      was 9.1 per 100,000 person-years (95% CI, 7.0-11.1 per 100,000 person-years). The
      incidence of microscopic colitis and its subtypes remained stable over the study
      period (P = .63). Increasing age (P < .001) and female sex (P < .001) were
      associated with increasing incidence. On December 31, 2010, the prevalence of
      microscopic colitis was 219 cases per 100,000 persons (90.4 per 100,000 persons
      for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis).
      CONCLUSION: The incidence of microscopic colitis in Olmsted County residents has
      stabilized and remains associated with female sex and increasing age.

PMID- 24120841
TI  - Risk of pure red cell aplasia in patients with hepatitis C receiving antiviral
      therapy and an erythropoiesis-stimulating agent.
AB  - Antibody-mediated pure red cell aplasia (PRCA) has been primarily observed in
      patients with chronic kidney disease treated with an erythropoiesis-stimulating
      agent (ESA); only a few anecdotal cases have been reported in other patient
      populations. We searched the Amgen Global Safety Adverse Event Database and
      identified 14 patients with hepatitis C who developed severe anemia, anti
      erythropoietin antibodies, and bone marrow biopsy-proven PRCA, while receiving
      interferon therapy (with or without ribavirin) and an ESA. During the follow-up
      period and after ESA treatment stopped, 11 patients no longer required
      transfusions and 3 did. Analysis of antibody isotypes showed that, contrary to
      reports of patients with chronic kidney disease, immunoglobulin G1 was the
      predominant isotype rather than immunoglobulin G4 (immunoglobulin G4 was detected
      in only 1 of 6 patients). Epitope mapping showed the anti-erythropoietin
      antibodies bound domains required for receptor binding. Therefore, the potential
      benefits of ESA therapy must be weighed against the risk for PRCA in patients
      with hepatitis C who are receiving treatment with interferon and ribavirin. 

PMID- 24120842
TI  - High degree of correlation between whole blood and PBMC expression levels of miR
      155 and miR-146a in healthy controls and rheumatoid arthritis patients.
AB  - Elevated expression of specific microRNAs (miRNA) in peripheral blood-derived
      mononuclear cells (PBMC), particularly miR-146a and miR-155, is associated with
      rheumatoid arthritis (RA). Whole blood has not been explored as a potential
      clinical material for monitoring the expression of miRNAs in RA. We sought to
      determine whether miRNA levels detected in whole blood samples correlated with
      those detected in simultaneously isolated peripheral blood-derived mononuclear
      cells (PBMC) from the same individuals, thus establishing the feasibility of
      using whole blood as a viable clinical material for monitoring miRNA expression
      in RA and other disorders. We demonstrated a highly significant linear
      correlation between miR-146a and miR-155 expression in PBMC and whole blood, from
      both healthy individuals and RA patients. Whole blood samples accurately reflect
      miRNA levels in PBMC and would be useful in monitoring the expression of miRNAs
      as biomarkers. The detection of miRNA levels in samples that are readily obtained
      in routine clinical practice, such as whole blood, enhances their potential
      utility in detecting changes in the immunological mechanisms underlying
      autoimmune diseases such as RA. 

PMID- 24120843
TI  - A method for high purity sorting of rare cell subsets applied to TDC.
AB  - T(DC) are a recently described subset of polyclonal alphabeta T-cells with
      dendritic cell properties. Because of their low number in peripheral immune
      compartments, isolation and characterization of T(DC) with existing purification
      methods are technically challenging. Here we describe a customized gating
      strategy and a flow cytometry-based cell sorting protocol for isolation of T(DC).
      The protocol was developed because, despite very conservative gating for dead
      cell and doublet exclusion, cells obtained with normal sorting procedures were
      enriched for T(DC) but not pure. Re-sorting the output of the first round of
      sorting results in highly pure T(DC). Cells obtained with this method are viable
      and can be used for in vitro characterization. Moreover, this double-round
      sorting strategy can be universally applied to the isolation of other rare cell
      subsets.

PMID- 24120844
TI  - Response to Bharmal et al. "The association of religiosity with overweight/obese
      body mass index among Asian Indian immigrants in California".

PMID- 24120845
TI  - Lipid-anchored SNAREs lacking transmembrane regions fully support membrane fusion
      during neurotransmitter release.
AB  - Synaptic vesicle fusion during neurotransmitter release is mediated by assembly
      of SNARE- and SM-protein complexes composed of syntaxin-1, SNAP-25, synaptobrevin
      2/VAMP2, and Munc18-1. Current models suggest that SNARE-complex assembly
      catalyzes membrane fusion by pulling the transmembrane regions (TMRs) of SNARE
      proteins together, thus allowing their TMRs to form a fusion pore. These models
      are consistent with the requirement for TMRs in viral fusion proteins. However,
      the role of the SNARE TMRs in synaptic vesicle fusion has not yet been tested
      physiologically. Here, we examined whether synaptic SNAREs require TMRs for
      catalysis of synaptic vesicle fusion, which was monitored electrophysiologically
      at millisecond time resolution. Surprisingly, we find that both lipid-anchored
      syntaxin-1 and lipid-anchored synaptobrevin-2 lacking TMRs efficiently promoted
      spontaneous and Ca(2+)-triggered membrane fusion. Our data suggest that SNARE
      proteins function during fusion primarily as force generators, consistent with
      the notion that forcing lipid membranes close together suffices to induce
      membrane fusion. 

PMID- 24120846
TI  - Probing the weak interaction of proteins with neutral and zwitterionic
      antifouling polymers.
AB  - Protein-polymer interactions are of great interest in a wide range of scientific
      and technological applications. Neutral poly(ethylene glycol) (PEG) and
      zwitterionic poly(sulfobetaine methacrylate) (pSBMA) are two well-known
      nonfouling materials that exhibit strong surface resistance to proteins. However,
      it still remains unclear or unexplored how PEG and pSBMA interact with proteins
      in solution. In this work, we examine the interactions between two model proteins
      (bovine serum albumin and lysozyme) and two typical antifouling polymers of PEG
      and pSBMA in aqueous solution using fluorescence spectroscopy, atomic force
      microscopy and nuclear magnetic resonance. The effect of protein:polymer mass
      ratios on the interactions is also examined. Collective data clearly demonstrate
      the existence of weak hydrophobic interactions between PEG and proteins, while
      there are no detectable interactions between pSBMA and proteins. The elimination
      of protein interaction with pSBMA could be due to an enhanced surface hydration
      of zwitterionic groups in pSBMA. New evidence is given to demonstrate the
      interactions between PEG and proteins, which are often neglected in the
      literature because the PEG-protein interactions are weak and reversible, as well
      as the structural change caused by hydrophobic interaction. This work provides a
      better fundamental understanding of the intrinsic structure-activity relationship
      of polymers underlying polymer-protein interactions, which are important for
      designing new biomaterials for biosensor, medical diagnostics and drug delivery
      applications. 

PMID- 24120847
TI  - Chemical sintering generates uniform porous hyaluronic acid hydrogels.
AB  - The implantation of scaffolds for tissue repair has achieved only limited success
      due primarily to the inability to achieve vascularization within the construct.
      Many strategies have therefore moved to incorporate pores into the scaffolds to
      encourage rapid cellular infiltration and subsequent vascular ingrowth. We
      utilized an efficient chemical sintering technique to create a uniform network of
      polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel
      formation. The porous hydrogels generated from chemical sintering possessed pore
      uniformity and interconnectivity comparable to the commonly used non- and heat
      sintering techniques. Moreover, a similar cell response to the porous hydrogels
      generated from each sintering approach was observed in cell viability, spreading
      and proliferation in vitro, as well as cellular invasion in vivo. We propose
      chemical sintering of PMMA microspheres using a dilute acetone solution as an
      alternative method to generate porous hyaluronic acid hydrogels since it requires
      equal or 10-fold less processing time as the currently used non-sintering or heat
      sintering technique, respectively. 

PMID- 24120848
TI  - Stop feeding cancer: pro-inflammatory role of visceral adiposity in liver cancer.
AB  - Liver cancer is the fifth most common cancer in the world with an estimated over
      half a million new cases diagnosed every year. Due to the difficulty in early
      diagnosis and lack of treatment options, the prevalence of liver cancer continues
      to climb with a 5-year survival rate of between 6% and 11%. Coinciding with the
      rise of liver cancer, the prevalence of obesity has rapidly increased over the
      past two decades. Evidence from epidemiological studies demonstrates a higher
      risk of hepatocellular carcinoma (HCC) in obese individuals. Obesity is
      recognised as a low-grade inflammatory disease, this is of particular relevance
      as inflammation has been proposed as the seventh hallmark of cancer development
      with abdominal visceral adiposity considered as an important source of pro
      inflammatory stimuli. Emerging evidence points towards the direct role of
      visceral adipose tissue rather than generalised body fat in carcinogenesis.
      Cytokines such as IL-6 and TNF-alpha secreted from visceral adipose tissue have
      been demonstrated to induce a chronic inflammatory condition predisposing the
      liver to a protumourigenic milieu. This review focuses on excess visceral
      adiposity rather than simple obesity; particularly adipokines and their
      implications for chronic inflammation, lipid accumulation, insulin resistance,
      Endoplasmic Reticulum (ER) stress and angiogenesis. Evidence of molecular
      signalling pathways that may give rise to the onset and progression of HCC in
      this context are depicted. Delineation of the pro-inflammatory role of visceral
      adiposity in liver cancer and its targeting will provide better rational and
      therapeutic approaches for HCC prevention and elimination. The concept of a
      central role for metabolism in cancer is the culmination of an effort that began
      with one of the 20th century's leading biochemists and Nobel laureate of 1931,
      Otto Warburg. 

PMID- 24120849
TI  - Cloning and sequence analysis of Peromyscus yucatanicus (Rodentia) Th1 (IL-12p35,
      IFN-gamma and TNF) and Th2 (IL-4, IL-10 and TGF-beta) cytokines.
AB  - The Yucatan deer mouse, Peromyscus yucatanicus (order Rodentia), is the principal
      reservoir of Leishmania (Leishmania) mexicana in the Yucatan peninsula of Mexico.
      Experimental infection results in clinical and histopathological features similar
      to those observed in humans with cutaneous leishmaniasis (CL) as well as
      peritoneal macrophage production of nitric oxide. These results support the
      possible use of P. yucatanicus as a novel experimental model to study CL caused
      by L. (L.) mexicana. However, immunological studies in these rodents have been
      limited by the lack of specific reagents. To address this issue, we cloned and
      analyzed cytokine sequences of P. yucatanicus as part of an effort to develop
      this species as a CL model. We cloned P. yucatanicus interleukin 4 (IL-4), IL-10,
      IL-12p35, gamma interferon, transforming growth factor beta and tumor necrosis
      factor partial cDNAs. Most of the P. yucatanicus sequences were highly conserved
      with orthologs of other mammalian species and the identity of all sequences were
      confirmed by the presence of conserved amino acids with possible biological
      functions in each putative polypeptide. The availability of these sequences is a
      first step which will allow us to carry out studies characterizing the immune
      response during pathogenic and nonpathogenic L. (L.) mexicana infections in P.
      yucatanicus. 

PMID- 24120850
TI  - IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from
      TGFbeta1-induced mesenchymal invasion.
AB  - TGFbeta1 is a major fibrotic factor and its actions involve induction of
      epithelial cell death, together with the stimulation and transdifferentiation of
      fibroblasts into collagen- and fibronectin-secreting myofibroblasts. These
      actions of TGFbeta1 are also consistent with a pro-metastatic role, by aiding
      epithelial cell escape through mesenchymal tissues. Recently IGFBP-5 has been
      described as a pro-fibrotic (pro-metastatic?) agent and the aim of this study was
      to compare and contrast the actions of IGFBP-5 with TGFbeta1. We used NMuMG cells
      and cloned stable epithelial and mesenchymal lines from the parent cells.
      TGFbeta1 induced apoptosis and/or EMT in the epithelial cells, whereas it
      enhanced mesenchymal cell survival and migration. IGFBP-5, in contrast, enhanced
      both cell-cell and cell-ECM adhesion and also improved wound closure in
      epithelial cells whereas, in mesenchymal cells, IGFBP-5 decreased adhesion and
      migration. Furthermore, IGFBP-5 was able to antagonise the actions of TGFbeta1.
      In a co-culture model simulating epithelial-mesenchymal boundaries, IGFBP-5 was
      able to antagonise the disruptive transgressions induced by TGFbeta1. Overall,
      these findings suggest that IGFBP-5 is important in maintaining epithelial
      mesenchymal boundaries and thus may limit metastasis and fibrosis by inducing an
      orderly repair mechanism, very distinct from the fibrotic disruption induced by
      TGFbeta1. A role for IGFBP-5 in the inhibition of metastasis is supported by
      immunohistochemical studies of breast cancer microarrays, where we show that
      elevated IGFBP-5 expression is associated with increased disease-free survival. 

PMID- 24120851
TI  - Resolvin D1 inhibits TGF-beta1-induced epithelial mesenchymal transition of A549
      lung cancer cells via lipoxin A4 receptor/formyl peptide receptor 2 and GPR32.
AB  - Epithelial-mesenchymal-transition (EMT) is a key event for tumor cells to
      initiate metastasis which lead to switching of E-cadherin to N-cadherin.
      Resolvins are known to promote the resolution of inflammation and phagocytosis of
      macrophages. However, the role of resolvins in EMT of cancer is not known.
      Therefore, we examined the effects of resolvins on transforming growth factor,
      beta 1 (TGF-beta1)-induced EMT. Expression of E-cadherin and N-cadherin in A549
      lung cancer cells was evaluated by Western blot and confocal microscopy.
      Involvement of lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) was
      examined by gene silencing. TGF-beta1 induced expression of N-cadherin in A549
      lung cancer cells, and resolvin D1 and D2 inhibited the expression of N-cadherin
      at low concentrations (1-100 nM). Resolvin D1 and D2 also suppressed the
      expression of zinc finger E-box binding homeobox 1 (ZEB1). The effects of
      resolvin D1 and D2 were confirmed in other lung cancer cell lines such as H838,
      H1299, and H1703. Resolvin D1 and D2 did not affect the proliferation of A549
      lung cancer cells. Resolvin D1 and D2 also suppressed the TGF-beta1-induced
      morphological change. Resolvin D1 and D2 also inhibited the TGF-beta1-induced
      migration and invasion of A549 cells. Resolvin D1 is known to act via ALX/FPR2
      and GPR32. Thus, we examined the involvement of ALX/FPR2 and GPR32 in the
      suppressive effects of resolvin D1 on TGF-beta1-induced EMT of A549 cells. Gene
      silencing of ALX/FPR2 and GPR32 blocked the action of resolvin D1. Overexpression
      of ALX/FPR2 or GPR32 increased the effects of resolvin D1. These results suggest
      that resolvin D1 inhibited TGF-beta1-induced EMT via ALX/FPR2 and GPR32 by
      reducing the expression of ZEB1.

PMID- 24120852
TI  - Interleukin 18: friend or foe in cancer.
AB  - In the last few years, the field of tumor immunology has significantly expanded
      and its boundaries, never particularly clear, have become less distinct. Although
      the immune system plays an important role in controlling tumor growth, it has
      also become clear that tumor growth can be promoted by inflammatory immune
      responses. A good example that exemplifies the ambiguous role of the immune
      system in cancer progression is represented by interleukin 18 (IL-18) that was
      first identified as an interferon-gamma-inducing factor (IGIF) involved in T
      helper type-1 (Th1) immune response. The expression and secretion of IL-18 have
      been observed in various cell types from immune cells to circulating cancer
      cells. In this review we highlighted the multiple roles played by IL-18 in immune
      regulation, cancer progression and angiogenesis and the clinical potential that
      may result from such understanding. 

PMID- 24120853
TI  - Glioma-homing peptide with a cell-penetrating effect for targeting delivery with
      enhanced glioma localization, penetration and suppression of glioma growth.
AB  - Tumor-targeted delivery systems are useful in enhancing drug delivery and
      increasing anti-tumor effects. Cell-penetrating peptides have been widely used
      for this purpose but have been hampered by the poor selectivity between
      neoplastic and non-neoplastic cells. As a peptide derived from interleukin-13,
      interleukin-13 peptide (IL-13p) is specifically targeted to IL13Ralpha2, a tumor
      restricted receptor. More interestingly, IL-13p possesses cell-penetrating
      properties that can specifically enhance the uptake by tumor cells compared with
      endothelial cells. Thus, we anchored IL-13p onto nanoparticles (ILNPs) for glioma
      targeting delivery. The uptake of ILNPs by U87 cells was higher than that of
      unmodified nanoparticles (NPs). However, there was no significant difference in
      the uptake by human umbilical vein endothelial cells. In addition, free IL-13p
      could also enhance the uptake of both NPs and ILNPs by U87 cells. Anchoring with
      IL-13p could enhance the penetration of particles into the core of spheroids. In
      vivo, the fluorescence intensity of ILNPs in tumors was 2.96-fold higher than
      that of NPs. The modification with IL-13p also significantly improved the speed
      and rate of penetration from vessels to tumor cells. The enhanced tumor
      localization of ILNPs was mostly attributable to the elevated tumor cell
      internalization of ILNPs, whereas most NPs were colocalized with microvessels or
      macrophages. Correspondingly, docetaxel-loaded NPs effectively suppressed the
      growth of subcutaneous U87 tumors. The average tumor volume of the ILNP group was
      only 31.4% that of the control, which was significantly smaller than that of the
      docetaxel and NP groups. In conclusion, the modification of IL-13p selectively
      enhanced tumor cell uptake, improved the penetration effect of NPs and improved
      the glioma localization ability, which led to a better tumor-suppression effect. 

PMID- 24120854
TI  - RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic
      RGD-modified liposomal-siRNA system.
AB  - Angiogenesis is one of crucial processes associated with tumor growth and
      development, and consequently a prime target for cancer therapy. Although tumor
      endothelial cells (TECs) play a key role in pathological angiogenesis,
      investigating phenotypical changes in neovessels when a gene expression in TEC is
      suppressed is a difficult task. Small interfering RNA (siRNA) represents a
      potential agent due to its ability to silence a gene of interest. We previously
      developed a system for in vivo siRNA delivery to cancer cells that involves a
      liposomal-delivery system, a MEND that contains a unique pH-sensitive cationic
      lipid, YSK05 (YSK-MEND). In the present study, we report on the development of a
      system that permits the delivery of siRNA to TECs by combining the YSK-MEND and a
      ligand that is specific to TECs. Cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) is a well
      known ligand to alphaVbeta3 integrin, which is selectively expressed at high
      levels in TECs. We incorporated cRGD into the YSK-MEND (RGD-MEND) to achieve an
      efficient gene silencing in TECs. Quantitative RT-PCR and the 5' rapid
      amplification of cDNA ends PCR indicated that the intravenous injection of RGD
      MEND at a dose of 4.0mg/kg induced a significant RNAi-mediated gene reduction in
      TEC but not in endothelial cells of other organs. Finally, we evaluated the
      therapeutic potency of the RGD-MEND encapsulating siRNA against vascular
      endothelial growth factor receptor 2. A substantial delay in tumor growth was
      observed after three sequential RGD-MEND injections on alternate days. In
      conclusion, the RGD-MEND represents a new approach for the characterization of
      TECs and for us in anti-angiogenic therapy. 

PMID- 24120855
TI  - Energy drink consumption among young Australian adults: associations with alcohol
      and illicit drug use.
AB  - BACKGROUND: Energy drinks are becoming increasingly popular among young people.
      The purpose of this study was to determine the prevalence of energy drink
      consumption and its associations with socio-demographic characteristics, alcohol,
      cigarette and illicit drug use in a population-based sample of young adults
      participating in the Western Australian Pregnancy Cohort (Raine) Study. METHODS:
      We used self-administered questionnaires to assess energy drink consumption
      patterns, alcohol intake, cigarette and illicit drug use at the 20-year cohort
      follow-up. Data was also collected on socio-demographics, physical activity, body
      mass index (BMI) and dietary intake. Our sample included 1234 participants (47%
      male, mean age 20 +/- 0.5 years). We considered energy-drink consumption as a
      categorical (users versus non-users) variable. RESULTS: Overall, 48% of
      participants consumed energy drinks at least once per month, with an average
      intake of 1.31 +/- 0.75 cans per day amongst energy drink users. The most
      significant correlates of energy drink use were being in part-time or full-time
      employment, being male, being a cigarette smoker, having heavier alcoholic spirit
      consumption patterns and being an ecstasy user (all p<0.05). No significant
      associations were observed with BMI or dietary intake. CONCLUSIONS: Australian
      energy drink users tend to have heavier alcohol consumption patterns be a
      cigarette smoker and use illicit drugs relative to non-users. More research is
      needed regarding the health risks associated with energy drink use in young
      adults, including their possible role in the development of substance abuse
      problems.

PMID- 24120856
TI  - The association of alcohol intake with gamma-glutamyl transferase (GGT) levels:
      evidence for correlated genetic effects.
AB  - BACKGROUND: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker
      for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism
      that is part of normal metabolism supposes a causal effect of alcohol intake on
      GGT. However, there is variability in the response of GGT to alcohol use, which
      may result from genetic differences between individuals. This study aimed to
      determine whether the epidemiological association between alcohol intake and GGT
      at the population level is necessarily a causal one or may also reflect effects
      of genetic pleiotropy (genes influencing multiple traits). METHODS: Data on
      alcohol intake (grams alcohol/day) and GGT, originating from twins, their
      siblings and parents (N=6465) were analyzed with structural equation models.
      Bivariate genetic models tested whether genetic and environmental factors
      influencing alcohol intake and GGT correlated significantly. Significant genetic
      and environmental correlations are consistent with a causal model. If only the
      genetic correlation is significant, this is evidence for genetic pleiotropy.
      RESULTS: Phenotypic correlations between alcohol intake and GGT were significant
      in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake
      correlated significantly with those for GGT, whereas the environmental factors
      were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT
      respectively). CONCLUSIONS: In this healthy population sample, the
      epidemiological association of alcohol intake with GGT is at least partly
      explained by genetic pleiotropy. Future longitudinal twin studies should
      determine whether a causal mechanism underlying this association might be
      confined to heavy drinking populations.

PMID- 24120857
TI  - The influence of depressive symptoms on alcohol use among HIV-infected Russian
      drinkers.
AB  - BACKGROUND: Depressive symptoms have been linked to HIV progression through a
      number of biobehavioral mechanisms including increased alcohol use. Although
      research supports an association between alcohol use and depressive symptoms
      among HIV patients, there have been few studies that have examined whether
      depressive symptoms predict subsequent drinking, especially among heavy drinking
      HIV-infected patients. METHOD: Heavy drinking Russian HIV-infected patients
      (n=700) were recruited from addiction and HIV care settings for a randomized
      controlled trial of a risk reduction intervention [HERMITAGE]. GEE overdispersed
      Poisson regression analyses were conducted to assess the association between
      depressive symptoms and alcohol consumption 6-months later. RESULTS: In adjusted
      analyses, depressive symptom severity was significantly associated with drinks
      per day (global p=.02). Compared to the non-depressed category, mild depressive
      symptoms were significantly associated with more drinks per day [IRR=1.55, (95%
      CI: 1.14, 2.09)], while moderate [IRR=1.14, (95% CI: 0.83, 1.56)] and severe
      [IRR=1.48, (95% CI: 0.93, 2.34)] depressive symptoms were not. Associations
      between depressive symptom severity and heavy drinking days were not
      statistically significant (global p=.19). Secondary analyses using the BDI-II
      screening threshold (BDI-II>14) and the BDI-II cognitive subscale suggested an
      association between depressive symptoms and drinks per day over time but not
      heavy episodic drinking. CONCLUSIONS: Among heavy drinking HIV-infected patients,
      elevated depressive symptoms were associated with greater subsequent alcohol use.
      These findings suggest that depressive symptoms may be important to address in
      efforts to reduce alcohol-related risks among HIV-infected populations.

PMID- 24120859
TI  - Functional interaction between HIV-gp120 and opioid system in the preoptic
      anterior hypothalamus.
AB  - BACKGROUND: Recently we found that fever (part of HIV-related wasting) is induced
      by the action of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein
      (gp120) in the preoptic anterior hypothalamus (POAH). As the opioid system plays
      a role in the pathogenesis of HIV-1, in the present study we sought to examine
      the capacity of the opioid system to regulate the febrile response induced by
      gp120. METHODS: Stainless steel cannulas were stereotactically into the POAH, and
      a biotelemetry system was used to monitor the body temperature (Tb changes). We
      examined the in vivo effects of naloxone as well as highly opioid-selective
      receptor antagonists, on gp120-induced fever. RESULTS: Pretreatment with naloxone
      or the mu-opioid receptor-selective antagonist, cyclic d-Phe-Cys-Tyr-d-Trp-Arg
      Thr-Pen-Thr-NH(2) (CTAP), significantly delayed the febrile response induced by
      gp120. In contrast, naltriben (NTB), a selective antagonist for the delta-2
      opioid receptor, did not cause any effect on gp120-induced fever. CONCLUSION:
      These results (1) provide pharmacologic evidence of a functional in vivo
      interaction between the opioid system and this viral protein in the POAH and (2)
      show that mu-opioid receptors can regulate gp120-induced fever.

PMID- 24120858
TI  - Modafinil restores methamphetamine induced object-in-place memory deficits in
      rats independent of glutamate N-methyl-D-aspartate receptor expression.
AB  - BACKGROUND: Chronic methamphetamine (meth) abuse in humans can lead to various
      cognitive deficits, including memory loss. We previously showed that chronic meth
      self-administration impairs memory for objects relative to their location and
      surrounding objects. Here, we demonstrate that the cognitive enhancer, modafinil,
      reversed this cognitive impairment independent of glutamate N-methyl-d-aspartate
      (GluN) receptor expression METHODS: Male, Long-Evans rats underwent a
      noncontingent (Experiment 1) or contingent (Experiment 2) meth regimen. After one
      week of abstinence, rats were tested for object-in-place recognition memory. Half
      the rats received either vehicle or modafinil (100mg/kg) immediately after object
      familiarization. Rats (Experiment 2) were sacrificed immediately after the test
      and brain areas that comprise the key circuitry for object in place performance
      were manually dissected. Subsequently, glutamate receptor expression was measured
      from a crude membrane fraction using Western blot procedures. RESULTS: Saline
      treated rats spent more time interacting with the objects in changed locations,
      while meth-treated rats distributed their time equally among all objects. Meth
      treated rats that received modafinil showed a reversal in the deficit, whereby
      they spent more time exploring the objects in the new locations. GluN2B receptor
      subtype was decreased in the perirhinal cortex, yet remained unaffected in the
      prefrontal cortex and hippocampus of meth rats. This meth-induced down regulation
      occurred whether or not meth experienced rats received vehicle or modafinil.
      CONCLUSIONS: These data support the use of modafinil for memory impairment in
      meth addiction. Further studies are needed to elucidate the neural mechanisms of
      modafinil reversal of cognitive impairments.

PMID- 24120860
TI  - The architecture of yeast DNA polymerase zeta.
AB  - DNA polymerase zeta (Polzeta) is specialized for the extension step of
      translesion DNA synthesis (TLS). Despite its central role in maintaining genome
      integrity, little is known about its overall architecture. Initially identified
      as a heterodimer of the catalytic subunit Rev3 and the accessory subunit Rev7,
      yeast Polzeta has recently been shown to form a stable four-subunit enzyme
      (Polzeta-d) upon the incorporation of Pol31 and Pol32, the accessory subunits of
      yeast Poldelta. To understand the 3D architecture and assembly of Polzeta and
      Polzeta-d, we employed electron microscopy. We show here how the catalytic and
      accessory subunits of Polzeta and Polzeta-d are organized relative to each other.
      In particular, we show that Polzeta-d has a bilobal architecture resembling the
      replicative polymerases and that Pol32 lies in proximity to Rev7. Collectively,
      our study provides views of Polzeta and Polzeta-d and a structural framework for
      understanding their roles in DNA damage bypass. 

PMID- 24120861
TI  - The organization of submodality-specific touch afferent inputs in the vibrissa
      column.
AB  - The rodent tactile vibrissae are innervated by several different types of touch
      sensory neurons. The central afferents of all touch neurons from one vibrissa
      collectively project to a columnar structure called a barrelette in the
      brainstem. Delineating how distinct types of sensors connect to second-order
      neurons within each barrelette is critical for understanding tactile information
      coding and processing. Using genetic and viral techniques, we labeled slowly
      adapting (SA) mechanosensory neurons, rapidly adapting (RA) mechanosensory
      neurons, afferent synapses, and second-order projection neurons with four
      different fluorescent markers to examine their connectivity. We discovered that
      within each vibrissa column, individual sensory neurons project collaterals to
      multiply distributed locations, inputs from SA and RA afferents are spatially
      intermixed without any discernible stereotypy or topography, and second-order
      projection neurons receive convergent SA and RA inputs. Our findings reveal a
      "one-to-many and many-to-one" connectivity scheme and the circuit architecture
      for tactile information processing at the first-order synapses. 

PMID- 24120863
TI  - A chemical glycoproteomics platform reveals O-GlcNAcylation of mitochondrial
      voltage-dependent anion channel 2.
AB  - Protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) is a
      critical cell signaling modality, but identifying signal-specific O-GlcNAcylation
      events remains a significant experimental challenge. Here, we describe a method
      for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated
      proteins and use it to identify the mitochondrial voltage-dependent anion channel
      2 (VDAC2) as an O-GlcNAc substrate. VDAC2(-/-) cells resist the mitochondrial
      dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating a
      functional connection between O-GlcNAc signaling and mitochondrial physiology
      through VDAC2. More broadly, our method will enable the discovery of signal
      specific O-GlcNAcylation events in a wide array of experimental contexts. 

PMID- 24120862
TI  - Bisphosphonates target B cells to enhance humoral immune responses.
AB  - Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone
      mass in patients. We show here that the administration of clinically relevant
      doses of bisphosphonates in mice increases antibody responses to live and
      inactive viruses, proteins, haptens, and existing commercial vaccine
      formulations. Bisphosphonates exert this adjuvant-like activity in the absence of
      CD4(+) and gammadelta T cells, neutrophils, or dendritic cells, and their effect
      does not rely on local macrophage depletion, Toll-like receptor signaling, or the
      inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell
      expansion and antibody production upon antigen encounter. These data establish
      bisphosphonates as an additional class of adjuvants that boost humoral immune
      responses.

PMID- 24120864
TI  - An extensive network of TET2-targeting MicroRNAs regulates malignant
      hematopoiesis.
AB  - The Ten-Eleven-Translocation 2 (TET2) gene, which oxidates 5-methylcytosine in
      DNA to 5-hydroxylmethylcytosine (5hmC), is a key tumor suppressor frequently
      mutated in hematopoietic malignancies. However, the molecular regulation of TET2
      expression is poorly understood. We show that TET2 is under extensive microRNA
      (miRNA) regulation, and such TET2 targeting is an important pathogenic mechanism
      in hematopoietic malignancies. Using a high-throughput 3' UTR activity screen, we
      identify >30 miRNAs that inhibit TET2 expression and cellular 5hmC. Forced
      expression of TET2-targeting miRNAs in vivo disrupts normal hematopoiesis,
      leading to hematopoietic expansion and/or myeloid differentiation bias, whereas
      coexpression of TET2 corrects these phenotypes. Importantly, several TET2
      targeting miRNAs, including miR-125b, miR-29b, miR-29c, miR-101, and miR-7, are
      preferentially overexpressed in TET2-wild-type acute myeloid leukemia. Our
      results demonstrate the extensive roles of miRNAs in functionally regulating TET2
      and cellular 5hmC and reveal miRNAs with previously unrecognized oncogenic
      potential. Our work suggests that TET2-targeting miRNAs might be exploited in
      cancer diagnosis. 

PMID- 24120866
TI  - Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus
      strain found in carcinomas.
AB  - The Epstein-Barr virus (EBV) is found in a variety of tumors whose incidence
      greatly varies around the world. A poorly explored hypothesis is that particular
      EBV strains account for this phenomenon. We report that M81, a virus isolated
      from a Chinese patient with nasopharyngeal carcinoma (NPC), shows remarkable
      similarity to other NPC viruses but is divergent from all other known strains.
      M81 exhibited a reversed tropism relative to common strains with a reduced
      ability to infect B cells and a high propensity to infect epithelial cells, which
      is in agreement with its isolation from carcinomas. M81 spontaneously replicated
      in B cells in vitro and in vivo at unusually high levels, in line with the
      enhanced viral replication observed in NPC patients. Spontaneous replication and
      epitheliotropism could be partly ascribed to polymorphisms within viral proteins.
      We suggest considering M81 and its closely related isolates as an EBV subtype
      with enhanced pathogenic potential. 

PMID- 24120865
TI  - Continuously tunable Ca(2+) regulation of RNA-edited CaV1.3 channels.
AB  - CaV1.3 ion channels are dominant Ca(2+) portals into pacemaking neurons, residing
      at the epicenter of brain rhythmicity and neurodegeneration. Negative Ca(2+)
      feedback regulation of CaV1.3 channels (CDI) is therefore critical for Ca(2+)
      homeostasis. Intriguingly, nearly half the CaV1.3 transcripts in the brain are
      RNA edited to reduce CDI and influence oscillatory activity. It is then
      mechanistically remarkable that this editing occurs precisely within an IQ
      domain, whose interaction with Ca(2+)-bound calmodulin (Ca(2+)/CaM) is believed
      to induce CDI. Here, we sought the mechanism underlying the altered CDI of edited
      channels. Unexpectedly, editing failed to attenuate Ca(2+)/CaM binding. Instead,
      editing weakened the prebinding of Ca(2+)-free CaM (apoCaM) to channels, which
      proves essential for CDI. Thus, editing might render CDI continuously tunable by
      fluctuations in ambient CaM, a prominent effect we substantiate in substantia
      nigral neurons. This adjustability of Ca(2+) regulation by CaM now looms as a key
      element of CNS Ca(2+) homeostasis. 

PMID- 24120867
TI  - Intermittent transcription dynamics for the rapid production of long transcripts
      of high fidelity.
AB  - Normal cellular function relies on the efficient and accurate readout of the
      genetic code. Single-molecule experiments show that transcription and replication
      are highly intermittent processes that are frequently interrupted by polymerases
      pausing and reversing directions. Although intermittent dynamics in replication
      are known to result from proofreading, their origin and significance during
      transcription remain controversial. Here, we theoretically investigate
      transcriptional fidelity and show that the kinetic scheme provided by the RNA
      polymerase backtracking and transcript-cleavage pathway can account for measured
      error rates. Importantly, we find that intermittent dynamics provide an enormous
      increase in the rate of producing long transcripts of high fidelity. Our results
      imply that intermittent dynamics during transcription may have evolved as a way
      to mitigate the competing demands of speed and fidelity in the transcription of
      extended sequences. 

PMID- 24120868
TI  - The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress.
AB  - Several proto-oncogenes and tumor suppressors regulate the production of
      ribosomes. Ribosome biogenesis is a major consumer of cellular energy, and
      defects result in p53 activation via repression of mouse double minute 2 (MDM2)
      homolog by the ribosomal proteins RPL5 and RPL11. Here, we report that RPL5 and
      RPL11 regulate p53 from the context of a ribosomal subcomplex, the 5S
      ribonucleoprotein particle (RNP). We provide evidence that the third component of
      this complex, the 5S rRNA, is critical for p53 regulation. In addition, we show
      that the 5S RNP is essential for the activation of p53 by p14(ARF), a protein
      that is activated by oncogene overexpression. Our data show that the abundance of
      the 5S RNP, and therefore p53 levels, is determined by factors regulating 5S
      complex formation and ribosome integration, including the tumor suppressor PICT1.
      The 5S RNP therefore emerges as the critical coordinator of signaling pathways
      that couple cell proliferation with ribosome production. 

PMID- 24120869
TI  - Using micromanipulation to analyze control of vertebrate meiotic spindle size.
AB  - The polymerization/depolymerization dynamics of microtubules (MTs) have been
      reported to contribute to control of the size and shape of spindles, but
      quantitative analysis of how the size and shape correlate with the amount and
      density of MTs in the spindle remains incomplete. Here, we measured these
      parameters using 3D microscopy of meiotic spindles that self-organized in Xenopus
      egg extracts and presented a simple equation describing the relationship among
      these parameters. To examine the validity of the equation, we cut the spindle
      into two fragments along the pole-to-pole axis by micromanipulation techniques
      that rapidly decrease the amount of MTs. The spheroidal shape spontaneously
      recovered within 5 min, but the size of each fragment remained small. The
      equation we obtained quantitatively describes how the spindle size correlates
      with the amount of MTs while maintaining the shape and the MT density. 

PMID- 24120870
TI  - BIM-mediated membrane insertion of the BAK pore domain is an essential
      requirement for apoptosis.
AB  - BAK activation represents a key step during apoptosis, but how it converts into a
      mitochondria-permeabilizing pore remains unclear. By further delineating the
      structural rearrangements involved, we reveal that BAK activation progresses
      through a series of independent steps: BH3-domain exposure, N-terminal change,
      oligomerization, and membrane insertion. Employing a "BCL-XL-addiction" model, we
      show that neutralization of BCL-XL by the BH3 mimetic ABT-737 resulted in death
      only when cells were reconstituted with BCL-XL:BAK, but not BCL-2/ BCL-XL:BIM
      complexes. Although this resembles the indirect model, release of BAK from BCL-XL
      did not result in spontaneous adoption of the pore conformation. Commitment to
      apoptosis required association of the direct activator BIM with oligomeric BAK
      promoting its conversion to a membrane-inserted pore. The sequential nature of
      this cascade provides multiple opportunities for other BCL-2 proteins to
      interfere with or promote BAK activation and unites aspects of the indirect and
      direct activation models. 

PMID- 24120871
TI  - Chromatin modifications sequentially enhance ErbB2 expression in ErbB2-positive
      breast cancers.
AB  - ErbB2 gene amplification occurs in 20%-25% of breast cancers, and its therapeutic
      targeting has markedly improved survival of patients with breast cancer in the
      adjuvant setting. However, resistance to these therapies can develop. Because
      epigenetic mechanisms can importantly influence oncogene expression and be
      druggable as well, we investigated histone modifications that influence ErbB2
      overexpression, independent of gene amplification. We demonstrate here that ErbB2
      overexpressing breast carcinomas acquire the H3K4me3 mark on the erbB2 promoter
      and that receptor-amplified tumors further acquire the H3K9ac mark, which is
      dependent on H3K4me3 mark acquisition. Targeting WD repeat domain 5 (Wdr5), which
      is absolutely required for H3K4me3 enrichment, decreased ErbB2 overexpression,
      associated with a decrease in the H3K4me3 mark on the erbB2 promoter. Of note,
      Wdr5 silencing cooperated with trastuzumab or chemotherapy in specifically
      inhibiting the growth of ErbB2-positive breast tumor cells. Thus, our studies
      illuminate epigenetic steps in the selection for ErbB2 activation. 

PMID- 24120872
TI  - Left atrial appendage morphology and silent cerebral ischemia in patients with
      atrial fibrillation.
AB  - BACKGROUND: Left atrial appendage (LAA) is the major source of cardiac thrombi in
      atrial fibrillation (AF) and plays a major role in cardioembolic events.
      OBJECTIVE: To investigate the correlation between LAA morphology and the burden
      of silent cerebral ischemia (SCI) as a new thromboembolic risk marker in patients
      with AF. METHODS: A total of 348 patients with AF undergoing transcatheter
      ablation were enrolled. A cerebral magnetic resonance (MR) was performed to
      assess SCI burden, while LAA morphology was studied by MR or computed tomography
      and categorized as follows: cactus in 52 (14.9%) patients, chicken wing in 177
      (50.9%), wind sock in 101 (29.0%), and cauliflower in 18 (5.2%). RESULTS: SCIs
      were detected in 295 (84.8%) patients, with a median number of lesions of 23. SCI
      burden was related to LAA complexity: 30.8% and 17.3% patients with cactus, 30.5%
      and 22.0% with chicken wing, 13.9% and 27.7% with wind sock, and 16.7% and 38.9%
      with cauliflower LAA morphologies were in the first and fourth quartiles of
      number of SCI per patient, respectively (P = .035). After adjustment for
      potential confounders, only age (beta 0.12; 95% CI 0.08-0.16; P < .001), chicken
      wing (beta -0.28; 95% CI -0.51 to -0.04; P = .021), wind sock (beta 0.38; 95% CI
      0.12-0.65; P = .005), and cauliflower (beta 0.61; 95% CI 0.07-1.14; P = .026) LAA
      morphologies were significantly related to SCI burden. CONCLUSION: LAA morphology
      relates to the burden of SCI in AF patients. Future research should corroborate
      if accessible methods (eg, echocardiography) are able to describe LAA morphology,
      permitting its use within universal thromboembolic risk predictors in AF
      patients.

PMID- 24120873
TI  - Myocardial repolarization dispersion and autonomic nerve activity in a canine
      experimental acute myocardial infarction model.
AB  - BACKGROUND: Evidence from a canine experimental acute myocardial infarction (MI)
      model shows that until the seventh week after MI, the relationship between
      stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA)
      progressively increases. OBJECTIVE: The purpose of this study was to evaluate how
      autonomic nervous system activity influences temporal myocardial repolarization
      dispersion at this period. METHODS: We analyzed autonomic nerve activity as well
      as QT and RR variability from recordings previously obtained in nine dogs. From a
      total of 48 short-term ECG segments, 24 recorded before and 24 recorded 7 weeks
      after experimentally-induced MI, we obtained three indices of temporal myocardial
      repolarization dispersion: QTe (from Q-wave to T-wave end), QTp (from Q-wave to T
      wave peak), and Te (from T-wave peak to T-wave end) variability index (QTeVI,
      QTpVI, TeVI). We also performed heart rate variability power spectral analysis on
      the same segments. RESULTS: After MI, all the QT variables increased QTeVI
      (median [interquartile range]) (from -1.76[0.82] to -1.32[0.68]), QTeVI (from 
      1.90[1.01] to -1.45[0.78]), and TeVI (from -0.72[0.67] to -0.22[1.00]), whereas
      all RR spectral indices decreased (P <.001 for all). Distinct circadian rhythms
      in QTeVI (P <.05,) QTpVI (P <.001) and TeVI (P <.05) appeared after MI with
      circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI
      acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI
      acrophase coincided with another SGNA/VNA peak. After MI, regression analysis
      detected a positive relationship between SGNA/VNA and TeVI (R(2): 0.077; beta:
      0.278; p< 0.001). CONCLUSION: Temporal myocardial repolarization dispersion shows
      a circadian variation after MI reaching its peak at a time when sympathetic is
      highest and vagal activity lowest.

PMID- 24120875
TI  - Current treatment of ventricular arrhythmias: state of the art.
AB  - Ventricular arrhythmias may be benign, requiring only evaluation for associated
      risks and then reassurance, or associated with a risk of sudden death or
      significant morbidity. Therapies for these arrhythmias have evolved considerably
      over the past 20 years. For some, a definitive, curative therapy is available in
      the form of catheter ablation. Others are best managed with an implantable
      cardioverter-defibrillator that provides effective arrhythmia termination and
      protection from sudden death, with antiarrhythmic drugs or ablation to control
      recurrent arrhythmias. Although progress has been substantial, many challenges
      remain. 

PMID- 24120874
TI  - Blockade of A2B adenosine receptor reduces left ventricular dysfunction and
      ventricular arrhythmias 1 week after myocardial infarction in the rat model.
AB  - BACKGROUND: Remodeling occurs after myocardial infarction (MI), leading to
      fibrosis, dysfunction, and ventricular tachycardias (VTs). Adenosine via the A2B
      adenosine receptor (A2BAdoR) has been implicated in promoting fibrosis.
      OBJECTIVE: To determine the effects of GS-6201, a potent antagonist of the
      A2BAdoR, on arrhythmogenic and functional cardiac remodeling after MI. METHODS:
      Rats underwent ischemia-reperfusion MI and were randomized into 4 groups: control
      (treated with vehicle), angiotensin-converting enzyme inhibitor (treated with
      enalapril 1 day after MI), GS-6201-1d (treated with GS-6201 1 day after MI), GS
      6201-1w (treated with GS-6201 administered 1 week after MI) . Echocardiography
      was performed at baseline and 1 and 5 weeks after MI. Optical mapping, VT
      inducibility, and histologic analysis were conducted at follow-up. RESULTS:
      Treatment with the angiotensin-converting enzyme inhibitor improved ejection
      fraction (57.8% +/- 2.5% vs 43.3% +/- 1.7% in control; P < .01), but had no
      effect on VT inducibility. Treatment with GS-6201 improved ejection fraction
      (55.6% +/- 2.6% vs 43.3% +/- 1.7% in control; P < .01) and decreased VT
      inducibility (9.1% vs 68.4% in control; P < .05). Conduction velocities were
      significantly higher at border and infarct zones in hearts of rats treated with
      GS-6201 than in those of other groups. The conduction heterogeneity index was
      also significantly lower in hearts of rats treated with GS-6201. Histologic
      analysis showed that while both GS-6201 and enalapril decreased fibrosis in the
      noninfarct zone, only GS-6201 reduced the heterogeneity of fibrosis at the
      border, which is consistent with its effect on VT reduction. CONCLUSIONS:
      Treatment with an A2BAdoR antagonist at 1 week results in the improvement in
      cardiac function and decreased substrate for VT. The inhibition of fibrogenesis
      by A2BAdoR antagonists may be a new target for the prevention of adverse
      remodeling after MI.

PMID- 24120876
TI  - Acute electrical and hemodynamic effects of multisite left ventricular pacing for
      cardiac resynchronization therapy in the dyssynchronous canine heart.
AB  - BACKGROUND: Multisite left ventricular (multi-LV) epicardial pacing has been
      proposed as an alternative to conventional single-site LV (single-LV) pacing to
      increase the efficacy of cardiac resynchronization therapy. OBJECTIVE: To compare
      the effects of multi-LV versus single-LV pacing in dogs with left bundle branch
      block (LBBB). METHODS: Studies were performed in 9 anaesthetized dogs with
      chronic LBBB using 7 LV epicardial electrodes. Each electrode was tested alone
      and in combination with 1, 2, 3, and 6 other electrodes, the sequence of which
      was chosen on the basis of practical real-time electrical mapping to determine
      the site of the latest activation. LV total activation time (LVTAT) and
      dispersion of repolarization (DRep) were measured by using approximately 100
      electrodes around the ventricles. LV contractility was assessed as the maximum
      derivative of left ventricular pressure (LVdP/dtmax ). RESULTS: Single-LV pacing
      provided, on average, a -4.0% +/- 9.3% change in LVTAT and 0.2% +/- 13.7% change
      in DRep. Multi-LV pacing markedly decreased both LVTAT and DRep in a stepwise
      fashion to reach -41.3% +/- 5% (P < .001 for overall comparison) and -14.2% +/-
      19.5% (P < .02 for overall comparison) in the septuple-LV pacing configuration,
      respectively. Single-LV pacing provided a mean increase of 10.7% +/- 7.7% in
      LVdP/dtmax. LVdP/dtmax incrementally increased by the addition of pacing
      electrodes to 16.4% +/- 8.7% (P < .001 for overall comparison). High response to
      single-LV pacing could not be improved further during multi-LV pacing.
      CONCLUSIONS: Compared with single-LV pacing, multi-LV pacing can considerably
      reduce both LVTAT and DRep in dogs with LBBB, but the improvement in
      contractility is limited to conditions where single-LV pacing provides suboptimal
      improvement. Further studies are warranted to determine whether these acute
      effects translate in antiarrhythmic properties and better long-term outcomes.

PMID- 24120877
TI  - Effect of prenatal stress on density of NMDA receptors in rat brain.
AB  - N-methyl-D-aspartate (NMDA) receptors are important excitatory receptors which
      contribute to many brain functions. Altered NMDA receptor levels cause
      maldevelopment of corticostriatal and corticolimbic pathways, which is a
      neurobiological predisposing factor for development of epilepsy, schizophrenia
      and other idiopathic psychotic disorders. It was hypothesized that prenatal
      stress could play a role in pathophysiology of these disorders by affecting
      expression of the receptors through releasing corticosterone. Sixty-eight virgin
      female Wistar rats were selected and mated with male rats with the same genotype.
      Then, the pregnant rats were subjected to restraint or predator stress on 15th,
      16th and 17th gestation days. Prenatal stress consisted of restraint or predator
      stresses of the dams under normal room conditions. After parturition, the pups
      were studied in terms of density of NMDA receptors in brain at different time
      points. Meanwhile, blood sample was obtained and corticosterone blood level (CBL)
      was measured. The pups were then compared with the pups born to unstressed dams.
      Stress induced significant rise in CBL and NMDA receptors in brain of the
      offspring. CBL was significantly higher among the stressed rats compared to the
      control ones; there was significant difference between the two stresses and
      between the two sexes. The male pups were affected more severely. Stressful
      events during gestation had important effects on NMDA receptors of the offspring.
      It can be concluded that stress-induced elevation of NMDA receptors and
      corticosterone might mediate altered susceptibility to epilepsy and decrease
      ability of learning and memory and other stress-induced neurologic disorders.

PMID- 24120878
TI  - Middle subtalar osseous coalition with associated fusion of the sinus tarsi: a
      previously undescribed type of tarsal coalition.
AB  - Tarsal coalitions affect up to 13% of the population and may cause chronic ankle
      and hindfoot pain. Coalitions can be subdivided as osseous, cartilaginous, or
      fibrous types. The most common type of tarsal coalition involvesthe talocalcaneal
      joint, where it usually affects the middle subtalar joint. In this article, we
      describe a previously unpublished form of talocalcaneal coalition with osseous
      coalition at the level of the middle subtalar joint with associated fusion of the
      sinus tarsi. 

PMID- 24120879
TI  - Current role and future potential of magnetic resonance cholangiopancreatography
      with an emphasis on incidental findings.
AB  - PURPOSE: Aim of this study was to investigate the incidence of relevant biliary
      and extrabiliary findings in patients undergoing magnetic resonance
      cholangiopancreatography (MRCP). MATERIALS AND METHODS: Three hundred eighty-four
      patients underwent 1.5-Tesla MRCP, and relevant biliary and extra-biliary
      findings were identified. RESULTS: Four hundred twenty-two biliary findings were
      identified in 384 patients (75%; 1.1 per patient). Ninety-five patients were free
      of any relevant biliary finding (25%). Incidental extrabiliary findings were
      observed in 763 patients (1.98/patient). CONCLUSION: Most of the findings can be
      diagnosed by MRCP, while others require further examination. Interdisciplinary
      involvement is recommended to optimize clinical categorization, management, and
      treatment of these incidental findings.

PMID- 24120880
TI  - Synthesis, characterization and biological evaluation of paeonol
      thiosemicarbazone analogues as mushroom tyrosinase inhibitors.
AB  - A series of hydroxy- and methoxy-substituted paeonol thiosemicarbazone analogues
      were synthesized as potential tyrosinase inhibitors and their inhibitory effects
      on mushroom tyrosinase and inhibitory mechanism were evaluated. Paeonol
      thiosemicarbazone analogues have been found exhibiting more remarkable inhibition
      than their indexcompounds on mushroom tyrosinase. Among them, compound 2,4
      dihydroxy acetophenone-4-phenyl-3-thiosemicarbazone (d1) had the most potent
      inhibition activity with the IC50 value of 0.006 +/- 0.001 mM, displayed as a
      reversible competitive inhibitor. The inhibitory ability of o- or p-substituted
      acetophenone thiosemicarbazones was: di-substituted acetophenone
      thiosemicarbazones>mono-substituted acetophenone thiosemicarbazones>non
      substituted acetophenone thiosemicarbazones. Copper ions chelation assay
      explained that compound d1 exhibited competitive inhibition by forming a chelate
      with the copper ions at the catalytic domain of tyrosinase as well as indicate a
      1.5:1 binding ratio of compound d1 with copper ions. In the fluorescence spectrum
      study, compound d1 behaved stronger fluorescence quenching on tyrosinase towards
      d1-Cu(2+) complex, inhibiting tyrosinase mainly by means of chelating the two
      copper ions in the active site. The newly synthesized compounds may serve as
      structural templates for designing and developing novel tyrosinase inhibitors.

PMID- 24120882
TI  - Physico-chemical characterization of the temperature dependent hydration kinetics
      of Gleditsia sinensis gum.
AB  - The physico-chemical properties and hydration kinetics of Gleditsia sinensis gum
      were investigated to evaluate its temperature dependence. The increase of
      temperature resulted in improved solubility of G. sinensis gum, and the dissolved
      galactomannan showed decreased degree of galactose substitution (DSGal) and
      increased molecular weight (p<0.05, ANOVA). The solubility of G. sinensis
      galactomannan at 25, 45, 60 and 80  degrees C was 73.4, 83.8, 98.1, and 99.4%,
      respectively. Weibull and Logarithmic models were well fitted (R(2)>0.96), and
      the hydration index t0.8 at different temperatures varied in the range of 51-302
      min. It was found that galactomannan with low DSGal and high molecular weight
      exhibited slow hydration rate and poor solubility.

PMID- 24120881
TI  - Incorporation of essential oil in alginate microparticles by multiple
      emulsion/ionic gelation process.
AB  - In this study, an o/w/o multiple emulsion/ionic gelation method was developed for
      production of alginate microparticles loaded with Satureja hortensis essential
      oil (SEO). It was found that the essential oil concentration has significant
      influence on encapsulation efficiency (EE), loading capacity (LC) and size of
      microparticles. The values of EE, LC and particle mean diameter were about 52
      66%, 20-26%, and 47-117 MUm, respectively, when the initial SEO content was 1-3%
      (v/v) .The essential oil-loaded microparticles were porous, as displayed by
      scanning electron micrograph. The presence of SEO in alginate microparticles was
      confirmed by Fourier transform-infrared (FT-IR) spectroscopy and differential
      scanning calorimetry (DSC) analyses. SEO-loaded microparticles showed good
      antioxidant (with DPPH radical scavenging activity of 40.7-73.5%) and
      antibacterial properties; this effect was greatly improved when the concentration
      of SEO was 3% (v/v). S. aureus was found to be the most sensitive bacterium to
      SEO and showed a highest inhibition zone of 304.37 mm(2) in the microparticles
      incorporated with 3% (v/v) SEO. In vitro release studies showed an initial burst
      release and followed by a slow release. In addition, the release of SEO from the
      microparticles followed Fickian diffusion with acceptable release.

PMID- 24120883
TI  - CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor.
AB  - Mechanisms controlling microtubule dynamics at the cell cortex play a crucial
      role in cell morphogenesis and neuronal development. Here, we identified kinesin
      4 KIF21A as an inhibitor of microtubule growth at the cell cortex. In vitro,
      KIF21A suppresses microtubule growth and inhibits catastrophes. In cells, KIF21A
      restricts microtubule growth and participates in organizing microtubule arrays at
      the cell edge. KIF21A is recruited to the cortex by KANK1, which coclusters with
      liprin-alpha1/beta1 and the components of the LL5beta-containing cortical
      microtubule attachment complexes. Mutations in KIF21A have been linked to
      congenital fibrosis of the extraocular muscles type 1 (CFEOM1), a dominant
      disorder associated with neurodevelopmental defects. CFEOM1-associated mutations
      relieve autoinhibition of the KIF21A motor, and this results in enhanced KIF21A
      accumulation in axonal growth cones, aberrant axon morphology, and reduced
      responsiveness to inhibitory cues. Our study provides mechanistic insight into
      cortical microtubule regulation and suggests that altered microtubule dynamics
      contribute to CFEOM1 pathogenesis.

PMID- 24120885
TI  - P-glycoprotein is responsible for the poor intestinal absorption and low toxicity
      of oral aconitine: in vitro, in situ, in vivo and in silico studies.
AB  - Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus
      Aconitum, some of which have been widely used as medicinal herbs for thousands of
      years. In this study, we systematically evaluated the potential role of P
      glycoprotein (P-gp) in the mechanisms underlying the low and variable
      bioavailability of oral AC. First, the bidirectional transport of AC across Caco
      2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of
      these two cell lines was greater than its influx. Additionally, the P-gp
      inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of
      AC. An in situ intestinal perfusion study in rats showed that verapamil co
      perfusion caused a significant increase in the intestinal permeability of AC,
      from 0.22*10(-5) to 2.85*10(-5) cm/s. Then, the pharmacokinetic profile of orally
      administered AC with or without pre-treatment with verapamil was determined in
      rats. With pre-treatment of verapamil, the maximum plasma concentration (Cmax) of
      AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold
      increase in the area under the plasma concentration-time curve (AUC0-12h) of AC
      was observed when co-administered with verapamil. In silico docking analyses
      suggested that AC and verapamil possess similar P-gp recognition mechanisms. This
      work demonstrated that P-gp is involved in limiting the intestinal absorption of
      AC and attenuating its toxicity to humans. Our data indicate that potential P-gp
      mediated drug-drug interactions should be considered carefully in the clinical
      application of aconite and formulations containing AC.

PMID- 24120884
TI  - DAF-2 and ERK couple nutrient availability to meiotic progression during
      Caenorhabditis elegans oogenesis.
AB  - Coupling the production of mature gametes and fertilized zygotes to favorable
      nutritional conditions improves reproductive success. In invertebrates, the
      proliferation of female germline stem cells is regulated by nutritional status.
      However, in mammals, the number of female germline stem cells is set early in
      development, with oocytes progressing through meiosis later in life. Mechanisms
      that couple later steps of oogenesis to environmental conditions remain largely
      undefined. We show that, in the presence of food, the DAF-2 insulin-like receptor
      signals through the RAS-ERK pathway to drive meiotic prophase I progression and
      oogenesis; in the absence of food, the resultant inactivation of insulin-like
      signaling leads to downregulation of the RAS-ERK pathway, and oogenesis is
      stalled. Thus, the insulin-like signaling pathway couples nutrient sensing to
      meiotic I progression and oocyte production in C. elegans, ensuring that oocytes
      are only produced under conditions favorable for the survival of the resulting
      zygotes. 

PMID- 24120886
TI  - Anthropometric characteristics and nutrition in a cohort of PAH-deficient
      patients.
AB  - BACKGROUND & AIMS: Treating phenylketonuria based upon strict vegetarian diets
      has occasionally been found to hamper physical development, some patients
      presenting with growth retardation and malnutrition. In addition, some
      researchers have reported an association between higher protein intakes and
      attaining better developmental outcomes, although it remains unclear which
      protein fraction (natural or synthetic) has the greatest influence on growth. The
      present study aimed to evaluate anthropometric characteristics and nutrition in a
      cohort of patients with phenylketonuria and mild-hyperphenylalaninaemia from
      birth to adulthood. METHODS: We conducted a retrospective longitudinal study
      comparing anthropometric characteristics (weight, height, body mass index, and
      growth rate) in our patients and healthy subjects, with the measurements
      expressed as z-scores. Nutritional issues were also considered. Data were
      collected every 6 months from birth to 18 years of age. RESULTS: Growth
      impairment was observed in phenylketonuric patients. Specifically, there were two
      well-differentiated periods throughout which height fell well below z-score = 0:
      from birth to two years of age, and on reaching adulthood. We also found height
      and weight to be positively correlated with phenylalanine intake. No growth
      retardation was seen in the patients with mild-hyperphenylalaninaemia.
      CONCLUSIONS: Phenylketonuric patients showed growth impairment in the early
      stages, with higher phenylalanine intakes being associated with attaining better
      developmental outcomes in this period. Therefore, prescribing very stringent
      diets in the early years might predispose phenylketonuric patients to retarded
      growth later in life, with growth outcomes in adulthood being well below the 50th
      percentile for healthy subjects.

PMID- 24120887
TI  - Transdermal delivery of relatively high molecular weight drugs using novel self
      dissolving microneedle arrays fabricated from hyaluronic acid and their
      characteristics and safety after application to the skin.
AB  - The purpose of this study was to develop novel dissolving microneedle arrays
      fabricated from hyaluronic acid (HA) as a material and to improve the transdermal
      permeability of relatively high molecular weight drugs. In this study,
      fluorescein isothiocyanate-labeled dextran with an average molecular weight of
      4kDa (FD4) was used as a model drug with a relatively high molecular weight. The
      microneedle arrays significantly increased transepidermal water loss (TEWL) and
      reduced transcutaneous electrical resistance (TER), indicating that they could
      puncture the skin and create drug permeation pathways successfully. Both TEWL and
      TER almost recovered to baseline levels in the microneedle array group, and
      relatively small pathways created by the microneedles rapidly recovered as
      compared with those created by a tape stripping treatment. These findings
      confirmed that the microneedle arrays were quite safe. Furthermore, we found that
      the transdermal permeability of FD4 using the microneedle arrays was much higher
      than that of the FD4 solution. Furthermore, we found that the microneedle arrays
      were much more effective for increasing the amount of FD4 accumulated in the
      skin. These findings indicated that using novel microneedle arrays fabricated
      from HA is a very useful and effective strategy to improve the transdermal
      delivery of drugs, especially relatively high molecular weight drugs without
      seriously damaging the skin. 

PMID- 24120888
TI  - The serological evidence in humans supports a negligible risk of zoonotic
      infection from porcine circovirus type 2.
AB  - There are two porcine circovirus (PCV) genotypes, PCV-1 and PCV-2. In pigs, PCV-1
      infection is asymptomatic but PCV-2 infection can cause severe respiratory
      disease and other pathology. Although humans ingest PCV-contaminated foods and
      are exposed to PCV through other sources, the potential of PCV-2 as a zoonotic
      agent in humans and other species has not been fully explored. Here, four
      recombinant proteins derived from the PCV-2 capsid gene were examined as antigens
      using the Luciferase Immunoprecipitation System (LIPS) assay for serological
      analysis of PCV-2 infection. PCV-2-CAP-Delta1 was the optimum recombinant protein
      in the LIPS assay with a sensitivity of 93% and specificity of 100% using porcine
      samples. Testing of healthy human blood donors, equine and bovine serum samples
      failed to demonstrate the presence of anti-PCV-2 antibodies. Additionally,
      analysis of two high-risk human groups, cystic fibrosis patients taking porcine
      derived oral supplements and type I diabetes patients who had undergone porcine
      islet cell transplantation, showed no evidence of anti-PCV-2 antibodies. These
      results extend the extensively demonstrated use of LIPS as a robust approach for
      identifying humoral responses and provide evidence that PCV-2 is likely not
      infectious in humans. 

PMID- 24120889
TI  - Entomopathogenic fungi in cornfields and their potential to manage larval western
      corn rootworm Diabrotica virgifera virgifera.
AB  - Entomopathogenic ascomycete fungi are ubiquitous in soil and on phylloplanes, and
      are important natural enemies of many soil-borne arthropods including larval
      western corn rootworm, Diabrotica virgifera virgifera, which is a major pest of
      corn. We measured the prevalence of Beauveria bassiana and Metarhizium anisopliae
      sensu lato in ten cornfields in Iowa, USA by baiting with larval insects. B.
      bassiana and M. anisopliae s.l. were present in 60% +/- 6.3% and 55% +/- 6.4% of
      soil samples, respectively. Subsequent laboratory bioassays found that some M.
      anisopliae s.l. strains collected from cornfields killed a greater proportion of
      D.v. virgifera larvae than a standard commercial strain.

PMID- 24120890
TI  - A unique orthogeriatric model: a step forward in improving the quality of care
      for hip fracture patients.
AB  - BACKGROUND: In August 2010, a unique model of shared care for hip fracture
      patients was implemented in our hospital. In this model, patients are allocated
      to an orthogeriatric team within 48 h of surgery, who review patients daily to
      manage medical complications and coordinate multidisciplinary rehabilitation,
      with orthopaedic input if necessary. AIM: To compare the new model to the
      previous model of care as perceived by members of staff and compare clinical
      outcomes. METHODS: Prospective data were collected using questionnaires given to
      medical, nursing and allied health professionals. Their opinions were rated using
      the Likert scaling system and analysed with the Mann Whitney U-test. Clinical
      outcomes were obtained from the hip fracture database and subsequently analysed.
      RESULTS: 59 responses (100%); 21 doctors and 38 allied health professionals. The
      majority of staff believed that quality of patient care was better in the newer
      model and preferred to work in this model. The median length of stay in the
      previous model (274 patients) was 25 days compared to 19.5 days in the new model
      (249 patients) (p = 0.22). 56.8% patients returned to their source of admission
      in the previous model compared to 72.7% in the new model (p = 0.00007). The
      inpatient mortality rates improved from 12.4% in the previous model to 8.4% in
      the new model (p = 0.26). CONCLUSION: This unique model improved care for hip
      fracture patients and was cost effective. Furthermore, it highlighted excellent
      staff satisfaction. This can pioneer a change in the management of hip fracture
      patients nationally and internationally.

PMID- 24120891
TI  - Innovators working hard to avoid patent exclusions in the US.

PMID- 24120892
TI  - Systems biology in drug discovery and development.
AB  - The complexity of human biology makes it challenging to develop safe and
      effective new medicines. Systems biology omics-based efforts have led to an
      explosion of high-throughput data and focus is now shifting to the integration of
      diverse data types to connect molecular and pathway information to predict
      disease outcomes. Better models of human disease biology, including more
      integrated network-based models that can accommodate multiple omics data types,
      as well as more relevant experimental systems, will help predict drug effects in
      patients, enabling personalized medicine, improvement of the success rate of new
      drugs in the clinic, and the finding of new uses for existing drugs. 

PMID- 24120893
TI  - In situ gelling systems: a strategy to improve the bioavailability of ophthalmic
      pharmaceutical formulations.
AB  - The low therapeutic efficacy exhibited by conventional ophthalmic solutions owing
      to precorneal elimination of the drug, drainage by gravity, nasolacrimal
      drainage, conjunctival absorption, and the absence of controlled release and of
      bioadhesive properties, can be overcome by the use of in situ gelling systems.
      The combination in the same formulation of different in situ gelling polymers
      with different stimuli-responsiveness mechanisms exploiting the unique
      physicochemical characteristics of the ocular tissues is one such strategy that
      has produced improved results compared with conventional systems. As we discuss
      here, the recent use of biodegradable and biocompatible polymers in colloidal
      carrier systems has proved to be the most effective strategy, resulting in the
      exponential increase of the bioavailability of the ophthalmic drugs. 

PMID- 24120894
TI  - Molecular cloning and characterization of SL3: a stem cell-specific SL RNA from
      the planarian Schmidtea mediterranea.
AB  - Spliced leader (SL) trans-splicing is a biological phenomenon, common among many
      metazoan taxa, consisting in the transfer of a short leader sequence from a small
      SL RNA to the 5' end of a subset of pre-mRNAs. While knowledge of the biochemical
      mechanisms driving this process has accumulated over the years, the functional
      consequences of such post-transcriptional event at the organismal level remain
      unclear. In addition, the fact that functional analyses have been undertaken
      mainly in trypanosomes and nematodes leaves a somehow fragmented picture of the
      possible biological significance and evolution of SL trans-splicing in
      eukaryotes. Here, we analyzed the spatial expression of SL RNAs in the planarian
      flatworm Schmidtea mediterranea, with the goal of identifying novel developmental
      paradigms for the study of trans-splicing in metazoans. Besides the previously
      identified SL1 and SL2, S. mediterranea expresses a third SL RNA described here
      as SL3. While, SL1 and SL2 are collectively expressed in a broad range of
      planarian cell types, SL3 is highly enriched in a subset of the planarian stem
      cells engaged in regenerative responses. Our findings provide new opportunities
      to study how trans-splicing may regulate the phenotype of a cell. 

PMID- 24120896
TI  - Transgene expression from CpG-reduced lentiviral gene delivery vectors in vitro.
AB  - Current viral gene delivery vectors for gene therapy are inefficient due to short
      lived transgene expression attributed to the cytosine-phosphate-guanine (CpG)
      motifs in the transgene. Here we assessed the effects of CpG motif reduction in
      lentiviral (LV) gene delivery context on the level and duration of reporter gene
      expression in Chinese Hamster Ovary (CHO) cells, Human Immortalized Myelogenous
      Leukemia (K562) cells and hematopoietic stem cells (HSCs). The cells were
      transduced with LV carrying Zero-CpG green fluorescent protein (ZGFP) reporter
      gene, LV/CMV/ZGFP. The GFP expression was compared to its non CpG-depleted GFP
      reporter gene LV (LV/CMV/GFP) counterpart. The LV/CMV/ZGFP exhibited prolonged
      transgene expression in CHO cells and HSCs up to 10 days and 14 days, in the
      respective cells. This effect was not seen in the transduced K562 cells, which
      may be due to the DNA hypomethylation status of the cancer cell line. Transgene
      copy number analysis verified that the GFP expression was not from pseudo
      transduction and the transgene remained in the genome of the cells throughout the
      period of the study. The modest positive effects from the LV/CMV/ZGFP suggest
      that the reduction of CpG in the LV construct was not substantial to generate
      higher and more prolonged transgene expression.

PMID- 24120897
TI  - United Arab Emirates: phylogenetic relationships and ancestral populations.
AB  - In the current report, 109 unrelated individuals from the United Arab Emirates
      (UAE) were typed across 15 autosomal short tandem repeat (STR) loci (D8S1179,
      D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D149S433, vWA,
      TPOX, D18S51, D5S818 and FGA) routinely employed in population genetics analyses
      and compared across a set of ethnically and geographically targeted reference
      collections. UAE, located at the southeastern most portion of the Arabian
      Peninsula, in the tri-continental crossroads connecting Africa, Europe and Asia,
      has been influenced by a number of human dispersal waves from a plethora of
      sources including the Paleolithic "Out of Africa" migrations, the exodus of
      Neolithic pastoral agriculturalists from the Fertile Crescent and Northern
      Africa, as well as more recent migrations from Asia and the Middle East. We found
      that despite the high levels of consanguinity that characterize UAE, this
      population is genetically highly heterogeneous. When compared to various world
      wide biogeographical regions, the Arabian Peninsula exhibits the highest intra
      population variance. Admixture analyses indicate that UAE and Bahrain uniquely in
      Arabia share 23.7% and 22.9%, respectively, of their DNA with Southwest Asian
      populations. Similar and complex Structure profiles are seen among Arabian
      Peninsula populations underscoring the high genetic diversity of the region.
      Although UAE shares a number of genetic characteristics in common with the rest
      of the populations in the Arabian Peninsula, it is unique in terms of its
      relative high Asian genetic component, likely the result of geographical
      proximity to Southwest Asia, west-bound waves of migration and socio-political
      ties with territories to the east.

PMID- 24120895
TI  - Increased FGF3 and FGF4 gene dosage is a risk factor for craniosynostosis.
AB  - Interstitial duplications involving chromosome 11q have rarely been reported in
      the literature and mainly represent large, cytogenetically detectable
      rearrangements associated with a wide and variable spectrum of neurodevelopmental
      disorders. We report on a patient affected by intellectual disability,
      craniosynostosis, and microcephaly. Array-CGH analysis identified a de novo 290
      kb interstitial duplication of chromosome 11q13.3 including the FGF3 and FGF4
      genes. Clinical comparison of our patient with those previously reported with
      overlapping 11q duplications allows us to define the minimal duplicated region
      associated with craniosynostosis and strongly supports the hypothesis that the
      constitutional increased dosage of the FGF3 and FGF4 genes is a risk factor for
      craniosynostosis in humans.

PMID- 24120898
TI  - The complete mitochondrial genome sequence of Sogatella furcifera (Horvath) and a
      comparative mitogenomic analysis of three predominant rice planthoppers.
AB  - The white-backed planthopper (WBPH), Sogatella furcifera (Horvath), is one of the
      most destructive pests of rice crops in many Asian countries. Using long-PCR and
      shotgun library methods, we sequenced the entire mitochondrial genomes (mt
      genomes) of two WBPH individuals. Total lengths of the mt-genome of the two WBPH
      individuals were 16,612 bp and 16,654 bp with an identical AT content of 76.19%.
      Among the 13 protein coding genes (PCGs), only nad5 used an atypical initiation
      codon GTG. Most of the tRNA genes had the typical cloverleaf secondary structure
      except that the dihydrouridine (DHU) arms in two trnS genes and the TPsiC arm of
      trnG gene did not form a stable stem-loop structure. Similar to the brown
      planthopper (BPH), Nilaparvata lugens (Stal), and the small brown planthopper
      (SBPH), Laodelphax striatellus (Fallen), some extraordinary features were
      observed in the WBPH mt-genome. These include similar gene rearrangement pattern,
      unusually short length of the atp8 gene and variable numbers of tandem repeat
      (VNTR) structure in control region. Interestingly, the same tandem repeat unit
      with stable secondary structure appeared in two different planthoppers, WBPH and
      SBPH, which belong to two different genera of the Delphacidae. This peculiar
      feature provides a direct evidence for the close relationship between the two
      planthoppers and updates our understanding of the evolutionary characteristics of
      mitochondrial control region. Comparison with two other predominant rice
      planthoppers (BPH and SBPH) revealed that different PCGs of mitochondria exhibit
      different evolutionary patterns.

PMID- 24120899
TI  - Chemical state of heterocyclic aromatic amines in grilled beef: evaluation by in
      vitro digestion model and comparison of alkaline hydrolysis and organic solvent
      for extraction.
AB  - During grilling of the roast beef the following heterocyclic aromatic amines were
      found: IQ=200.6 ng 100g(-1), MeIQx=719.8 ng 100 g(-1), MeIQ=532.9 ng 100g(-1),
      4.8-diMeIQx=755.4 ng 100 g(-1), norharmane=507.0 ng 100 g(-1), harmane=1952.6 ng
      100 g(-1), Phe-P 1=263.7 ng 100 g(-1), Trp-P 2=559.2 ng 100 g(-1), PhIP=1179.8 ng
      100 g(-1) and AalphaC=51.7 ng 100g(-1). Their content was tested by using the
      method based on alkaline hydrolysis of the sample and the method based on solvent
      extraction of the grilled meat samples at different temperatures (without
      hydrolysis). The study showed that the heterocyclic aromatic amines produced
      during the grilling of beef are in a free form and chemically or physico
      chemically bonded. The chemical forms of HAA formed in food have never been
      studied. For the purpose of the partial confirmation that HAA may be chemically
      or physico-chemically bonded, grilled beef samples were digested in vitro in
      model segments of the human digestive tract. Digestive enzymes, particularly
      proteolytic enzymes caused a statistically significant increase of free HAA
      determined by using solvent extraction without prior chemical hydrolysis of the
      sample.

PMID- 24120900
TI  - Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet
      B induced skin cancer of mice: mitochondria mediated apoptotic signalling
      cascades.
AB  - Skin cancer is increasing at an alarming rate and becoming resistant to
      conventional chemotherapy necessitating improved drug delivery system. We loaded
      apigenin (Ap), a dietary flavonoid having anti-cancer property, with poly (lactic
      co-glycolide) (PLGA) nanoparticles (NAp) to explore if nano-encapsulation could
      enhance anti-carcinogenic effect against ultra-violet B (UVB) and Benzo(a)pyrene
      (BaP) induced skin tumor and mitochondrial dysfunction in mice. Particle size,
      morphology and zeta potential of NAp were determined using dynamic light
      scattering and atomic force microscopy. Tumor incidence and multiplicity in UVB
      BaP induced mice with/without NAp treatment were ascertained and their
      histolopathological sections and chromosomal aberrations were studied. ROS
      accumulation and mitochondrial functioning through relevant markers like
      mitochondrial transmembrane potential were analyzed. Mitochondrial volume
      changes/swelling, cytochrome c (cyt c) release, mRNA and protein expressions of
      Apaf-1, bax, bcl-2, cyt c, cleaved caspase-9 and 3 were studied. Results showed
      that NAp produced better effects than Ap, due to their smaller size, and faster
      mobility. NAp reduced tissue damage and frequency of chromosomal aberrations,
      increased ROS accumulation to mediate mitochondrial-apoptosis through modulation
      of several apoptotic markers and mitochondrial matrix swelling. NAp showed
      ameliorative potentials in combating skin cancer and therefore has greater
      prospect of use in therapeutic management of skin cancer. 

PMID- 24120901
TI  - Inhibitory effects of Pycnogenol(r) (French maritime pine bark extract) on airway
      inflammation in ovalbumin-induced allergic asthma.
AB  - Pycnogenol(r) (PYC) is a standardized extracts from the bark of the French
      maritime pine (Pinus maritime) and used as a herbal remedy for various diseases.
      In this study, we evaluated the effects of PYC on airway inflammation using a
      model of ovalbumin (OVA)-induced allergic asthma and RAW264.7 cells. PYC
      decreased nitric oxide production and reduced the interleukine (IL)-1beta and IL
      6 levels in LPS-stimulated RAW264.7 cells. PYC also reduced the expression of
      inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 and
      enhanced the expression of hemeoxygenase (HO)-1. In the in vivo experiment, PYC
      decreased the inflammatory cell count and the levels of IL-4, IL-5, IL-13, and
      immunoglobulin (Ig) E in BALF or serum. These results are consistent with the
      histological analysis findings, which showed that PYC attenuated the airway
      inflammation and mucus hypersecretion induced by OVA challenge. In addition, PYC
      enhanced the expression of HO-1. In contrast, PYC inhibited the elevated
      expression of iNOS and MMP-9 proteins induced by OVA challenge. In conclusion,
      PYC exhibits protective effects against OVA-induced asthma and LPS-stimulated
      RAW264.7 cells. These results suggest that PYC has potential as a therapeutic
      agent for the treatment of allergic asthma. 

PMID- 24120902
TI  - Contribution of dietary patterns to blood heavy metal concentrations in Korean
      adults: findings from the Fifth Korea National Health and Nutrition Examination
      Survey 2010.
AB  - The aim of the present study was to evaluate the associations between dietary
      patterns and blood levels of lead and mercury in Korean adults. A total of 858
      Korean adults (>=20 years) who participated in the Korea National Health and
      Nutrition Examination Survey (KNHANES) V-1 2010 were included in this study. Data
      of biochemical measurements including blood lead and mercury levels, nutrients
      intakes and anthropometric measurements were acquired. 'Balanced diet', 'Grain
      and kimchi', and 'Alcohol and noodle' dietary patterns were derived from a factor
      analysis, and the subjects were divided into tertiles by each dietary pattern
      score. A logistic multiple regression analysis showed that the balanced diet
      pattern was negatively associated with blood levels of lead before and after
      adjustment. On the other hand, the alcohol and noodle pattern was positively
      associated with blood lead and mercury levels. These results indicate that the
      alcohol and noodle dietary pattern characterized by high alcohol consumption and
      lack of various foods, and the balanced dietary pattern, including vegetable,
      fish, meat and milk intake, was associated with the blood concentrations of heavy
      metals in Korean adults.

PMID- 24120903
TI  - Treatment of the edentulous atrophic maxilla using zygomatic implants: evaluation
      of survival rates over 5-10 years.
AB  - The aim of this retrospective observational cohort study was to analyse and
      report the 5-10-year survival rates of endosseous zygomatic implants used in the
      rehabilitation of the atrophic maxilla. Forty-three consecutive zygomatic implant
      placements in 25 patients were evaluated over a 5-10-year period. All zygomatic
      implant surgery was carried out under general anaesthesia. Nobel Biocare
      zygomatic machined-surface implants were used, and placement was undertaken using
      the modified sinus slot method. The main outcome measures and determinants for
      success were survival of the restored implants and the proportion of originally
      planned prostheses delivered to patients. Of the 25 patients treated, 12 were
      male and 13 were female; 19 were non-smokers, and the mean age at time of surgery
      was 64 years. Patients were treatment-planned for implant-retained bridgework, a
      removable prosthesis retained by fixed cast gold or milled titanium beams, or
      magnet-retained removable prostheses. A combination of zygomatic and conventional
      implants was used in all but one patient. In this study it was shown that the
      overall success rate for zygomatic implants was 86%, with six of the implants
      either failing to integrate or requiring removal due to persistent infection
      associated with the maxillary sinus. All patients received their planned
      prosthesis, although in six cases the method of retention required modification.
      This study illustrates that zygomatic implants are a successful and important
      treatment option when trying to restore the atrophic maxilla, with the potential
      to avoid additional augmentation/grafting procedures and resulting in a high long
      term success rate. 

PMID- 24120904
TI  - United States medical school graduate interest in radiology residency programs as
      depicted by online search tools.
AB  - Recent media publications have indicated a tough job market in medical specialty
      positions for medical school graduates, specifically in the field of radiology.
      Internet search tools, such as Google Trends, have proved useful in the
      prediction of certain diseases on the basis of the search volume index for a
      specific term. The authors hypothesized that online search tools might be useful
      in the prediction of US medical school graduates' interest in residency positions
      in radiology. Google Trends indicated an increase over time in searches for
      "radiology salary" and a decrease over time in searches for "radiology
      residency." National Resident Matching Program results for diagnostic radiology
      showed an increase from 2004 to 2009 in the percentage of US graduates entering
      radiology but a dramatic drop from 2010 to 2013. This occurred even while the
      total number of US graduates active in the National Resident Matching Program
      increased. This finding might have been foretold on the basis of online query
      result trends. Online search data may be a useful insight into the interests of
      US medical school graduates and may be predictive of unfilled radiology residency
      positions and eventual increased shortages of community radiologists coming from
      US medical schools. 

PMID- 24120905
TI  - The boy who cried wolf, stat!

PMID- 24120906
TI  - Anthrax of the lower lip.
AB  - Anthrax of the oral cavity and oropharynx is well known, whereas anthrax of the
      lips is very rare. We present a case of anthrax of the lower lip in a 57-year-old
      man. The infection was characterized by a wide, black eschar, surrounded by
      vesicles, crusts, and erythematous-edematous halo, with submandibular and
      laterocervical lymphadenopathy. The oral cavity, oropharynx, and tonsils were
      normal. Laboratory examinations revealed leukocytosis and increased inflammatory
      markers. Otolaryngologic, gastrointestinal, lung, and neurologic examinations
      were negative. The patient was successfully treated with oral ciprofloxacin.
      Although rare, anthrax should be considered in the differential clinical
      diagnosis in patients returning from areas where this disease is endemic. 

PMID- 24120907
TI  - The study by Manfredini et al. used the Myotronics K6 device contrary to the
      device's published indications for use.

PMID- 24120908
TI  - Neuropathic pain after orthognathic surgery.
AB  - OBJECTIVE: This study assesses the incidence of neuropathic pain after
      orthognathic surgery at our center and briefly reports the cases found. STUDY
      DESIGN: All records of orthognathic surgical patients between 2001 and 2011 were
      exported from the hospital information system into a Portable Document Format
      platform (Adobe Acrobat) to simplify keyword searching. Records of patients that
      developed debilitating chronic pain were isolated and examined. RESULTS: Records
      included 982 bilateral sagittal split osteotomies, 536 LeFort I procedures, and
      335 surgically assisted rapid palatal expansion procedures. Six records were
      identified that described cases in which patients developed debilitating chronic
      neuropathic pain after orthognathic surgery (mean age at surgery, 43 years).
      CONCLUSIONS: The exposure of the inferior alveolar nerve or partial axonal injury
      together with a disruption of the bony environment of the inferior alveolar nerve
      is a risk factor after bilateral sagittal split osteotomy.

PMID- 24120909
TI  - Evaluation of the sternal intraosseous route as alternative emergency vascular
      access for the dental office: a manikin and cadaver model pilot study.
AB  - OBJECTIVE: To evaluate 2 sternal intraosseous access devices as alternatives to
      emergency intravenous access for dentists, using a manikin and a cadaver model.
      STUDY DESIGN: A group of 37 students performed a sternal intraosseous access on a
      manikin using a Vidacare kit including a puncture template and a prepuncture skin
      incision. Five months later, 9 of the students used the Vidacare and 8 used an
      Illinois needle (without template and incision) on adult human cadavers. India
      ink was injected as a tracer. RESULTS: Shorter times were recorded on cadavers
      compared with manikins in both systems. One Vidacare puncture ended
      subcutaneously. Two Illinois needle punctures perforated the sternum, one with
      intense mediastinal ink traces. Vidacare punctures took longer compared with
      Illinois needle punctures (medians, 32 vs 12 seconds; P = .0002). CONCLUSIONS:
      Template use to identify the sternal puncture position, combined with additional
      prepuncture skin incision, may be more efficient and less predisposed to severe
      complications for dentists' emergency use.

PMID- 24120910
TI  - Management recommendations for invasive dental treatment in patients using oral
      antithrombotic medication, including novel oral anticoagulants.
AB  - OBJECTIVE: The aims were (1) to search the scientific literature from 2007 to
      2012 for guidelines and new studies on the dental management of patients using
      oral antithrombotic medication; (2) to summarize the articles' evidence and
      recommendations; and (3) to propose an updated clinical practice guideline for
      general dentists. STUDY DESIGN: A systematic literature search in MEDLINE,
      Embase, and the Guideline websites, from October 2007 to October 2012, produced
      articles that were critically evaluated. RESULTS: The systematic literature
      search for guidelines yielded 74 citations (MEDLINE, 45; Embase, 22; and the
      Guideline websites, 7). Of these, only 2 guideline publications and 2 systematic
      reviews met the inclusion criteria. They yielded 32 recommendations. CONCLUSIONS:
      The evidence and subsequent recommendations from published guidelines all point
      in the same direction: do not interrupt oral antithrombotic medication, not even
      dual antiplatelet therapy, in simple dental procedures.

PMID- 24120912
TI  - Enigmas of cardiac troponin T phosphorylation.

PMID- 24120911
TI  - Impaired bile acid handling and aggravated liver injury in mice expressing a
      hepatocyte-specific RXRalpha variant lacking the DNA-binding domain.
AB  - BACKGROUND & AIMS: Retinoid X Receptor alpha (RXRalpha) is the principal
      heterodimerization partner of class II Nuclear Receptors (NRs), and a major
      regulator of gene expression of numerous hepatic processes, including bile acid
      (BA) homeostasis through multiple partners. Specific contributions of hepatic
      RXRalpha domains in heterodimer function in response to either BA load or
      ductular cholestasis are not fully characterized. METHODS: Wild-type (WT) mice
      and mice expressing a hepatocyte-specific RXRalpha lacking the DNA-Binding-Domain
      (hs-RxralphaDeltaex4(-/-)), which retains partial ability to heterodimerize with
      its partners, were fed a 1% cholic acid (CA) diet for 5 days, a 3,5
      diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 3 weeks, or control diet.
      RESULTS: Serum ALT (6.5-fold; p<0.05), AST (9.3-fold; p=0.06) and BA (2.8-fold;
      p<0.05) were increased in CA-fed hs-RxalphaDeltaex4(-/-) mice compared to CA-fed
      WT mice, but were equally induced between genotypes by DDC-feeding. CA-feeding
      elevated total (4.4-fold; p=0.06) and unconjugated (2.2-fold; p<0.02) bilirubin
      levels in hs-RxralphaDeltaex4(-/-) mice compared to WT mice, but not in DDC-fed
      hs-RxralphaDeltaex4(-/-) mice. Increased necrosis and inflammation was observed
      in CA-fed, but not in DDC-fed hs-RxralphaDeltaex4(-/-) mice. Apoptotic markers
      DR5, CK8, CK18 RNA were increased in CA- and DDC-fed hs-RxralphaDeltaex4(-/-)
      mice. Cleaved caspase 3, CK18 and p-JNK protein were elevated in CA-fed but not
      in DDC-fed hs-RxralphaDeltaex4(-/-) mice. Induction of Ostbeta and Cyp2b10 RNA
      was impaired in CA-fed and DDC-fed hs-RxralphaDeltaex4(-/-) mice. Surprisingly,
      DDC-fed hs-RxralphaDeltaex4(-/-) mice showed attenuated fibrosis compared to DDC
      fed WT mice. CONCLUSIONS: These two models of cholestasis identify common and
      injury-specific roles for RXRalpha heterodimers and the functional relevance of
      an intact RXRalpha-DBD in the hepatocytic adaptive cholestatic response.

PMID- 24120913
TI  - Analysis of vitamin D metabolism gene expression in human bone: evidence for
      autocrine control of bone remodelling.
AB  - The metabolism of 25-hydroxyvitamin D (25D) to active 1alpha,25-dihydroxyvitamin
      D (1,25D) by endogenous expression of 25D 1-alpha hydroxylase (CYP27B1) in bone
      cells appears to have functional effects in both osteoclasts and osteoblasts. To
      examine relationships between CYP27B1 expression in bone and its potential
      function in vivo, we examined the expression of vitamin D metabolism genes
      (CYP27B1, CYP24A1, VDR) in human trabecular bone samples and compared them by
      linear regression analysis with the expression of osteoclast (TRAP, CA2, CATK,
      NFATC1), osteoblast (TNAP, COL1A1, OCN, MEPE, BRIL), osteocyte (DMP1, SOST, PHEX,
      MEPE, FGF23)-related gene markers, genes associated with osteoblast/osteocyte
      control of osteoclastogenesis (RANKL, M-CSF, OPG, IL-8, TWEAK) and transcription
      factors (NFATC1, RUNX2, OSX, MSX2, HIF1A). This revealed multiple significant
      gene expression relationships between CYP27B1 and the transcription factors
      RUNX2, NFATC1, consistent with the coordinated expression of this gene by both
      osteoblast and osteoclast-lineage cells, and with MSX2 and the hypoxia-inducible
      transcription factor, HIF1A. CYP27B1 expression associated mainly with gene
      markers of bone resorption. VDR mRNA expression was also associated with
      resorption-related genes. Against expectations, CYP27B1 expression did not
      associate with bone expressed genes known to be 1,25D responsive, such as OCN,
      RANKL and DMP1. The major implication of these relationships in gene expression
      is that endogenous 1,25D synthesis and the response to 1,25D in human trabecular
      bone is linked with coordinated functions in both the osteoclastic and
      osteoblastic compartments towards the control of bone remodelling. This article
      is part of a Special Issue entitled '16th Vitamin D Workshop'. 

PMID- 24120914
TI  - Calcitriol reduces thrombospondin-1 and increases vascular endothelial growth
      factor in breast cancer cells: implications for tumor angiogenesis.
AB  - Calcitriol, a potent antineoplastic vitamin D metabolite, inhibits proliferation,
      induces apoptosis and slows the growth of tumors. Calcitriol also may exert
      either antiangiogenic or proangiogenic effects depending on the tissue. Vascular
      endothelial growth factor (VEGF) and thrombospondin-1 (Tsp-1) are key factors
      involved in promoting and inhibiting angiogenesis, respectively. The effects of
      calcitriol on Tsp-1 have not been studied in the mammary gland, while VEGF
      regulation is not clear, since opposite outcomes have been demonstrated.
      Therefore, the present study was undertaken to investigate the effects of
      calcitriol on VEGF and Tsp-1 expression in primary breast tumor-derived cells and
      a panel of established breast cancer cell lines. In vivo studies in athymic mice
      were also performed in order to gain further insight into the biological effects
      of calcitriol on angiogenesis. Real time-PCR and ELISA analyses showed that
      calcitriol stimulated VEGF mRNA expression and protein secretion while elicited
      the opposite effect on Tsp-1 in 7 out of 8 cell lines studied, independently of
      the cell phenotype (P<0.05 in n=5). In vivo, calcitriol significantly inhibited
      the relative tumoral volume after 4 weeks of treatment; however, serum VEGF was
      higher in calcitriol-treated animals compared to controls (P<0.05). The
      integrated fluorescence intensity analysis of CD31, a vessel marker, showed that
      xenografted breast cancer cells developed tumors with similar vascular density
      regardless of the treatment. Nevertheless, larger necrotic areas were observed in
      the tumors of calcitriol-treated mice compared to controls. Since the
      antineoplastic activity of calcitriol has been consistently demonstrated in
      several studies including this one, our results suggest that the antitumoral
      effect of calcitriol in vivo involve different mechanisms not necessarily related
      to the inhibition of tumor vascularization. Overall, our findings indicate that
      calcitriol can impact the angiogenic process in breast cancer by regulating VEGF
      and Tsp-1 expression. This article is part of a Special Issue entitled '16th
      Vitamin D Workshop'. 

PMID- 24120915
TI  - Role of proinflammatory cytokines on expression of vitamin D metabolism and
      target genes in colon cancer cells.
AB  - Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are
      proinflammatory cytokines that play a critical role in inflammatory bowel
      disease, as well as in colorectal tumorigenesis. We hypothesize that these
      cytokines modulate the expression and thus activity of the vitamin D system in
      colonic epithelial cells. We treated the colon cancer cell line COGA-1A for 6,
      12, and 24h with 1,25-dihydroxyvitamin D3 (1,25-D3), IL-6, TNFalpha, and with
      combinations of these compounds. Using quantitative RT-PCR, we analyzed mRNA
      expression of genes activating and catabolizing 1,25-D3 (1alpha-hydroxylase
      (CYP27B1), 24-hydroxylase (CYP24A1)), expression of several vitamin D target
      genes, as well as expression of cyclooxygenase 2 (COX-2) and 15
      hydroxyprostaglandin dehydrogenase. As expected, treatment with 1,25-D3 resulted
      in an upregulation of CYP24A1, whereas expression of CYP27B1 was not affected.
      Treatment with TNFalpha and IL-6 led to decreased expression of the vitamin D
      activating enzyme CYP27B1. The strong inflammatory property of TNFalpha was
      mirrored by its activation of COX-2 and inhibition of prostaglandin E2 (PGE2)
      catabolism. Interestingly, expression of the calcium ion channel TRPV6 was
      markedly decreased by TNFalpha. We conclude from these results that the presence
      of proinflammatory cytokines might impair activation of 1,25-D3, limiting its
      anti-inflammatory action. This article is part of a Special Issue entitled '16th
      Vitamin D Workshop'. 

PMID- 24120916
TI  - Estrogen reduces endoplasmic reticulum stress to protect against glucotoxicity
      induced-pancreatic beta-cell death.
AB  - Estrogen can improve glucose homeostasis not only in diabetic rodents but also in
      humans. However, the molecular mechanism by which estrogen prevents pancreatic
      beta-cell death remains unclear. To investigate this issue, INS-1 cells, a rat
      insulinoma cell line, were cultured in medium with either 11.1mM or 40mM glucose
      in the presence or the absence of estrogen. Estrogen significantly reduced
      apoptotic beta-cell death by decreasing nitrogen-induced oxidative stress and the
      expression of the ER stress markers GRP 78, ATF6, P-PERK, PERK, uXBP1, sXBP1, and
      CHOP in INS-1 cells after prolonged culture in medium with 40mM glucose. In
      contrast, estrogen increased the expression of survival proteins, including
      sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA-2), Bcl-2, and P-p38, in INS-1
      cells after prolonged culture in medium with 40mM glucose. The cytoprotective
      effect of estrogen was attenuated by addition of the estrogen receptor (ERalpha
      and ERbeta) antagonist ICI 182,780 and the estrogen membrane receptor inhibitor
      G15. We showed that estrogen decreases not only oxidative stress but also ER
      stress to protect against 40mM glucose-induced pancreatic beta-cell death. 

PMID- 24120917
TI  - Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent
      lipid raft internalization in docosahexaenoic acid-induced apoptosis.
AB  - Lipid rafts, plasma membrane microdomains, are important for cell survival
      signaling and cholesterol is a critical lipid component for lipid raft integrity
      and function. DHA is known to have poor affinity for cholesterol and it
      influences lipid rafts. Here, we investigated a mechanism underlying the anti
      cancer effects of DHA using a human breast cancer cell line, MDA-MB-231. We found
      that DHA decreased cell surface levels of lipid rafts via their internalization,
      which was partially reversed by cholesterol addition. With DHA treatment,
      caveolin-1, a marker for rafts, and EGFR were colocalized with LAMP-1, a
      lysosomal marker, in a cholesterol-dependent manner, indicating that DHA induces
      raft fusion with lysosomes. DHA not only displaced several raft-associated onco
      proteins, including EGFR, Hsp90, Akt, and Src, from the rafts but also decreased
      total levels of those proteins via multiple pathways, including the proteasomal
      and lysosomal pathways, thereby decreasing their activities. Hsp90 overexpression
      maintained its client proteins, EGFR and Akt, and attenuated DHA-induced cell
      death. In addition, overexpression of Akt or constitutively active Akt attenuated
      DHA-induced apoptosis. All these data indicate that the anti-proliferative effect
      of DHA is mediated by targeting of lipid rafts via decreasing cell surface lipid
      rafts by their internalization, thereby decreasing raft-associated onco-proteins
      via proteasomal and lysosomal pathways and decreasing Hsp90 chaperone function. 

PMID- 24120918
TI  - Combined LC/MS-platform for analysis of all major stratum corneum lipids, and the
      profiling of skin substitutes.
AB  - Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid
      classes in human stratum corneum (SC, outermost skin layer), but no studies
      report on the detailed analysis of these classes in a single platform. The
      primary aims of this study were to 1) develop an LC/MS method for (semi
      )quantitative analysis of all main lipid classes present in human SC; and 2) use
      this method to study in detail the lipid profiles of human skin substitutes and
      compare them to human SC lipids. By applying two injections of 10MUl, the
      developed method detects all major SC lipids using RPLC and negative ion mode
      APCI-MS for detection of FFAs, and NPLC using positive ion mode APCI-MS to
      analyze CERs and cholesterol. Validation showed this lipid platform to be robust,
      reproducible, sensitive, and fast. The method was successfully applied on ex vivo
      human SC, human SC obtained from tape strips and human skin substitutes (porcine
      SC and human skin equivalents). In conjunction with FFA profiles, clear
      differences in CER profiles were observed between these different SC sources.
      Human skin equivalents more closely mimic the lipid composition of human stratum
      corneum than porcine skin does, although noticeable differences are still
      present. These differences gave biologically relevant information on some of the
      enzymes that are probably involved in SC lipid processing. For future research,
      this provides an excellent method for (semi-)quantitative, 'high-throughput'
      profiling of SC lipids and can be used to advance the understanding of skin
      lipids and the biological processes involved. 

PMID- 24120919
TI  - Pro-fibrotic activity of lysophosphatidic acid in adipose tissue: in vivo and in
      vitro evidence.
AB  - Lysophosphatidic acid (LPA) is a pro-fibrotic mediator acting via specific
      receptors (LPARs) and is synthesized by autotaxin, that increases with obesity.
      We tested whether LPA could play a role in adipose tissue (AT)-fibrosis
      associated with obesity. Fibrosis [type I, III, and IV collagens (COL),
      fibronectin (FN), TGFbeta, CTGF and alphaSMA] and inflammation (MCP1 and F4/80)
      markers were quantified: (i) in vivo in inguinal (IAT) and perigonadic (PGAT) AT
      from obese-diabetic db/db mice treated with the LPAR antagonist Ki16425
      (5mg/kg/day ip for 7 weeks); and (ii) in vitro in human AT explants in primary
      culture for 72h in the presence of oleoyl-LPA (10MUM) and/or Ki16425 (10MUM)
      and/or the HIF-1alpha inhibitor YC-1 (100MUM). Treatment of db/db mice with
      Ki16425 reduced Col I and IV mRNAs in IAT and PGAT while Col III mRNAs were only
      reduced in IAT. This was associated with reduction of COL protein staining in
      both IAT and PGAT. AT explants showed a spontaneous and time-dependent increase
      in ATX expression and production of LPA in the culture medium, along with
      increased levels of Col I and III, TGFbeta and alphaSMA mRNAs and of COL protein
      staining. In vitro fibrosis was blocked by Ki16425 and was further amplified by
      oleoyl-LPA. LPA-dependent in vitro fibrosis was blocked by co-treatment with YC1.
      Our results show that endogenous and exogenous LPA exert a pro-fibrotic activity
      in AT in vivo and in vitro. This activity could be mediated by an LPA1R-dependent
      pathway and could involve HIF-1alpha.

PMID- 24120920
TI  - Extracellular metabolism-dependent uptake of lysolipids through cultured
      monolayer of differentiated Caco-2 cells.
AB  - Glycerophospholipids are known to be hydrolyzed in the intestinal lumen into free
      fatty acids and lysophospholipids that are then absorbed by the intestinal
      epithelial cells. A monolayer of enterocyte-differentiated Caco-2 cell is often
      used to assess the intestinal bioavailability of nutrients. In this study, we
      examined how differentiated Caco-2 cells process lysoglycerolipids such as
      lysophosphatidylcholine (LPC). Our findings were twofold. (1) Caco-2 cells
      secreted both a lysophospholipase A-like enzyme and a glycerophosphocholine
      phosphodiesterase enzyme into the apical, but not basolateral, lumen, suggesting
      that food-derived LPC is converted to a free fatty acid, sn-glycerol-3-phosphate,
      and choline through two sequential enzymatic reactions in humans. The release of
      the latter enzyme was differentiation-dependent. (2) Fatty acid-releasing
      activities toward exogenous fluorescent LPC, lysophosphatidic acid and
      monoacylglycerol were shown to be higher on the apical membranes of Caco-2 cells
      than on the basolateral membranes. These results suggest that human intestinal
      epithelial cells metabolize lysoglycerolipids by two distinct mechanisms
      involving secreted or apical-selective expression of metabolic enzymes. 

PMID- 24120921
TI  - Differential TLR2 downstream signaling regulates lipid metabolism and cytokine
      production triggered by Mycobacterium bovis BCG infection.
AB  - The nuclear receptor PPARgamma acts as a key modulator of lipid metabolism,
      inflammation and pathogenesis in BCG-infected macrophages. However, the molecular
      mechanisms involved in PPARgamma expression and functions during infection are
      not completely understood. Here, we investigate signaling pathways triggered by
      TLR2, the involvement of co-receptors and lipid rafts in the mechanism of
      PPARgamma expression, lipid body formation and cytokine synthesis in macrophages
      during BCG infection. BCG induces NF-kappaB activation and increased PPARgamma
      expression in a TLR2-dependent manner. Furthermore, BCG-triggered increase of
      lipid body biogenesis was inhibited by the PPARgamma antagonist GW9662, but not
      by the NF-kappaB inhibitor JSH-23. In contrast, KC/CXCL1 production was largely
      dependent on NF-kappaB but not on PPARgamma. BCG infection induced increased
      expression of CD36 in macrophages in vitro. Moreover, CD36 co-immunoprecipitates
      with TLR2 in BCG-infected macrophages, suggesting its interaction with TLR2 in
      BCG signaling. Pretreatment with CD36 neutralizing antibodies significantly
      inhibited PPARgamma expression, lipid body formation and PGE2 production induced
      by BCG. Involvement of CD36 in lipid body formation was further confirmed by
      decreased BCG-induced lipid body formation in CD36 deficient macrophages.
      Similarly, CD14 and CD11b/CD18 blockage also inhibited BCG-induced lipid body
      formation, whereas TNF-alpha synthesis was not affected. Disruption of rafts
      recapitulates the latter result, inhibiting lipid body formation, but not TNF
      alpha synthesis in BCG-infected macrophages. In conclusion, our results suggest
      that CD36-TLR2 cooperation and signaling compartmentalization within rafts,
      divert host response signaling through PPARgamma-dependent and NF-kappaB
      independent pathways, leading to increased macrophage lipid accumulation and down
      modulation of macrophage response. 

PMID- 24120922
TI  - Colour stability, staining and roughness of silorane after prolonged chemical
      challenges.
AB  - OBJECTIVES: To investigate the effect of prolonged chemical challenges on colour
      stability, staining susceptibility, and roughness of a silorane composite
      material when compared to methacrylate-based composites. METHODS: Initial colour
      and roughness were registered for specimens fabricated from methacrylate or
      silorane composites. Specimens were individually stored at 37 degrees C in 0.02 N
      citric acid, 0.02 N phosphoric acid, 75% ethanol or distilled water for 7, 14, 21
      and 180 days, when new measurements were performed. A staining test was performed
      after the chemical challenge by immersion in coffee during 3 weeks at 37 degrees
      C. Colour changes were characterized using the CIEL a b colour system. Data were
      submitted to analysis of variance for repeated measures, two-way analysis of
      variance and Tukey's multiple comparison test (alpha=0.05). RESULTS: Colour
      changes on the methacrylate-based resins were considered acceptable (although
      significantly different) after immersion in water, citric acid, phosphoric acid
      or ethanol, but were unacceptable for the silorane composite immersed in ethanol
      for 180 days. The methacrylate-based resins stored in ethanol were significantly
      more stained by coffee than those stored in other media. The silorane composite
      demonstrated no staining, but increased roughness, when compared to the
      methacrylate-based resins. CONCLUSIONS: No effect of the immersion solution was
      noticed on roughness of the investigated materials. Ethanol influenced colour
      stability and staining susceptibility differently for the methacrylate-based and
      silorane composites. CLINICAL SIGNIFICANCE: The knowledge of how acids and
      solvents affect the properties of tooth-coloured restorative materials is one of
      the decision-making criteria for the selection of a restorative material.

PMID- 24120923
TI  - Usefulness of Wada test in predicting seizure outcome following anterior temporal
      lobectomy.
AB  - OBJECTIVE: To study the usefulness of the Wada test for predicting seizure
      outcome following anterior temporal lobectomy (ATL). METHODS: From 1996 to 2002,
      all patients with left mesial temporal lobe epilepsy and hippocampal sclerosis
      (MTLE-HS) and selected patients with right MTLE-HS underwent the Wada test before
      ATL at our center. Patients were selected for ATL on the basis of unilateral HS
      on MRI and concordant electro-clinical data. Twelve-item recognition paradigm was
      used for Wada memory testing. Score of +1 was awarded for a correct response and 
      0.5 for an incorrect response. We defined Wada failure as a contralateral score
      of <5, ipsilateral score of >8, and difference score of <0. No patient was denied
      surgery based on the Wada results. Means of the three scores were compared
      between seizure free and non-seizure free patients. Sensitivity, specificity and
      receiver operator characteristic curves of various scores for predicting seizure
      outcome were calculated. RESULTS: 151 patients (129 left MTLE; mean age: 27.80+/
      8.72 years) formed the study group. At mean postoperative follow-up of 6.4+/-2.0
      years, 127 patients were seizure free. Mean contralateral score was lower in the
      seizure-free group (7.15+/-3.07 vs. 8.71+/-4.13; p<0.001) while ipsilateral and
      difference scores were similar between the two seizure outcome groups. Areas
      under the curves for contralateral, ipsilateral and difference scores for
      predicting seizure-free outcome were 0.49, 0.58 and 0.59, respectively,
      suggesting its modest usefulness in individual patients. Results remained same
      when the analysis was restricted to left MTLE patients. CONCLUSIONS: Wada test
      has limited usefulness for predicting seizure outcome following ATL.

PMID- 24120924
TI  - Knee flexor strength and endurance profiles after ipsilateral hamstring tendons
      anterior cruciate ligament reconstruction.
AB  - OBJECTIVES: To profile knee flexor strength and endurance responses to
      ipsilateral hamstring tendon autograft anterior cruciate ligament reconstruction
      in patients, and to describe knee flexor strength and endurance as predictors of
      subjective outcomes. The hypothesis was that the involved leg would demonstrate
      deficits compared with uninvolved and matched legs. DESIGN: Retrospective cohort.
      SETTING: Controlled laboratory. PARTICIPANTS: Women (n=15; mean age, 20.47+/
      1.96y; height, 1.69+/-.08m; weight, 68.51+/-12.64kg), who were a mean +/- SD of
      25.93+/-11.25 months postsurgery, were matched to 15 sex-matched controls (mean
      age, 20.93+/-1.22y; height, 1.65+/-.06m; weight, 66.52+/-10.69kg). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Concentric peak flexor moment over the
      entire isokinetic joint range of motion, peak flexor moment at 105 degrees  of
      joint flexion, and knee flexor total work, normalized to body mass, and
      subjective questionnaire scores for the involved leg. RESULTS: Significantly
      lesser peak flexor moment over the entire isokinetic joint range of motion
      (P=.034) and total work (P=.048) existed for the involved leg (.959+/-.186Nm/kg;
      21.933+/-5.881J/kg) compared with the matched leg (1.108+/-.134Nm/kg; 27.431+/
      6.499J/kg). Significantly lesser peak flexor moment at 105 degrees  of joint
      flexion (P=.002) existed between the involved (.221+/-.116Nm/kg) and uninvolved
      (.40+/-.234Nm/kg) and matched (.475+/-.183Nm/kg) legs. Significantly greater
      strength deficits (P<=.001) existed at peak flexor moment at 105 degrees  of
      joint flexion compared with peak flexor moment over the entire isokinetic joint
      range of motion for side (53.83%+/-38.8%; 9.87%+/-10.77%) and group (77.61%+/
      44.14%; 18.09%+/-11.73%) differences. Peak flexor moment at 105 degrees  of joint
      flexion was a significant predictor of subjective pain (P=.007), symptoms
      (P=.006), function (P=.011), and sports (P=.022) outcomes. CONCLUSIONS: Knee
      flexor strength and endurance deficits suggest susceptibility to reinjury, and
      strength in a deep joint angle predicts subjective outcomes.

PMID- 24120925
TI  - Sonochemical preparation of pure t-LaVO4 nanoparticles with the aid of
      tris(acetylacetonato)lanthanum hydrate as a novel precursor.
AB  - Herein a simple and fast method is introduced for the synthesis of lanthanum
      orthovanadate (LaVO4) nanoparticles under ultrasound irradiation. The effect of
      tris(acetylacetonato)lanthanum hydrate ([La(acac)3.3H2O]) and La(OAc)3 as two
      different precursors on the morphology and phase purity of LaVO4 was
      investigated. To optimum the particle size of the products, sonication time and
      the kind of surfactants have been changed. The as-synthesized products were
      characterized by XRD, FT-IR, SEM, TEM, and EDS. Based on the obtained results, it
      was found that the size and shape of the sonochemically formed LaVO4
      nanoparticles were dramatically dependent on the sonication time, type of
      surfactant and lanthanum precursor. According to the XRD results, it was observed
      that pure tetragonal phase lanthanum orthovanadate (t-LaVO4) could be obtained
      only by using [La(acac)3.3H2O] as precursor under ultrasound irradiation for 30
      min. On the other hand, monoclinic phase lanthanum orthovanadate (m-LaVO4) with
      poor crystallinity has been produced by vigorous stirring at room temperature
      without sonication.

PMID- 24120927
TI  - Advisory Committee on Immunization Practices: notes from guest lecture at the
      14th annual meeting of the Japanese Society for Vaccinology.

PMID- 24120926
TI  - Prospective assessment of the prevalence of pelvic, paraaortic and high
      paraaortic lymph node metastasis in endometrial cancer.
AB  - OBJECTIVE: To prospectively define the prevalence of lymph node metastasis (LNM)
      in at risk endometrial cancer (EC). METHODS: From 2004 to 2008, frozen section
      based Mayo Criteria prospectively identified patients "not at-risk" of LNM (30%
      EC population; grade I/II, <50% myometrial invasion and tumor diameter <= 2 cm)
      where lymphadenectomy was not recommended. The remaining 70% EC cohort was
      considered "at-risk" of LNM; where a systematic pelvic and infrarenal paraaortic
      lymphadenectomy was recommended. Patients were prospectively followed. The area
      between renal vein and inferior mesenteric artery (IMA) was labeled as high
      paraaortic area. For calculating the prevalence of LNM in high paraaortic area,
      the denominator was the population with known anatomic location of nodal tissue
      in relation to the IMA. RESULTS: Of the 742 patients, 514 were at risk; of which
      89% underwent recommended lymphadenectomy. A mean (+/- standard deviation) of 36
      (+/- 14) pelvic and 18 (+/- 9) paraaortic nodes were harvested. The prevalence of
      pelvic and paraaortic LNM was 17% and 12%, respectively. In presence of pelvic
      LNM, 51% had paraaortic LNM. In absence of pelvic LNM, 3% had paraaortic LNM; of
      which 67% was located exclusively in high paraaortic area. Among patients with
      paraaortic LNM, 88% had high paraaortic LNM; and 35% had only high paraaortic
      LNM. The cases of paraaortic LNM with negative pelvic nodes seemed to cluster in
      moderate to high grade endometrioid EC with >= 50% myometrial invasion.
      CONCLUSION: We present reference data for the prevalence of LNM in at-risk EC
      patients to guide lymphadenectomy decisions for clinical and research purposes.

PMID- 24120928
TI  - Aspirin for prophylaxis against cerebral aneurysm rupture.

PMID- 24120929
TI  - Reconnaissance mission to the neurosurgical department in Kijabe Hospital, Kenya:
      a call for the submission of ideas and strategies.

PMID- 24120930
TI  - Validation protocol of analytical procedures for quantification of drugs in
      polymeric systems for parenteral administration: dexamethasone phosphate disodium
      microparticles.
AB  - In this work a protocol to validate analytical procedures for the quantification
      of drug substances formulated in polymeric systems that comprise both drug
      entrapped into the polymeric matrix (assay:content test) and drug released from
      the systems (assay:dissolution test) is developed. This protocol is applied to
      the validation two isocratic HPLC analytical procedures for the analysis of
      dexamethasone phosphate disodium microparticles for parenteral administration.
      Preparation of authentic samples and artificially "spiked" and "unspiked" samples
      is described. Specificity (ability to quantify dexamethasone phosphate disodium
      in presence of constituents of the dissolution medium and other microparticle
      constituents), linearity, accuracy and precision are evaluated, in the range from
      10 to 50 MUg mL(-1) in the assay:content test procedure and from 0.25 to 10 MUg
      mL(-1) in the assay:dissolution test procedure. The robustness of the analytical
      method to extract drug from microparticles is also assessed. The validation
      protocol developed allows us to conclude that both analytical methods are
      suitable for their intended purpose, but the lack of proportionality of the
      assay:dissolution analytical method should be taken into account. The validation
      protocol designed in this work could be applied to the validation of any
      analytical procedure for the quantification of drugs formulated in controlled
      release polymeric microparticles.

PMID- 24120931
TI  - Activating KIR molecules and their cognate ligands prevail in children with a
      diagnosis of ASD and in their mothers.
AB  - The activity of natural killer (NK) cells is modulated by the interaction between
      killer-cell immune globulin-like receptor (KIR) proteins and their cognate HLA
      ligands; activated NK cells produce inflammatory cytokines and mediate innate
      immune responses. Activating KIR/HLA complexes (aKIR/HLA) were recently suggested
      to prevail in children with autism spectrum disorders (ASD), a neurodevelopmental
      syndrome characterized by brain and behavioral abnormalities and associated with
      a degree of inflammation. We verified whether such findings could be confirmed by
      analyzing two sample cohorts of Sardinian and continental Italian ASD children
      and their mothers. Results showed that aKIR/HLA are increased whereas inhibitory
      KIR/HLA complexes are reduced in ASD children; notably this skewing was even more
      significant in their mothers. KIR and HLA molecules are expressed by placental
      cells and by the trophoblast and their interactions result in immune activation
      and influence fetal, as well as central nervous system development and
      plasticity. Data herein suggest that in utero KIR/HLA immune interactions favor
      immune activation in ASD; this may play a role in the pathogenesis of the
      disease. 

PMID- 24120932
TI  - High dietary protein restores overreaching induced impairments in leukocyte
      trafficking and reduces the incidence of upper respiratory tract infection in
      elite cyclists.
AB  - The present study examined whether a high protein diet prevents the impaired
      leukocyte redistribution in response to acute exercise caused by a large volume
      of high-intensity exercise training. Eight cyclists (VO2max: 64.2+/-6.5mLkg(
      1)min(-1)) undertook two separate weeks of high-intensity training while
      consuming either a high protein diet (3gkg(-1)proteinBM(-1)day(-1)) or an energy
      and carbohydrate-matched control diet (1.5gkg(-1)proteinBM(-1)day(-1)). High
      intensity training weeks were preceded by a week of normal-intensity training
      under the control diet. Leukocyte and lymphocyte sub-population responses to
      acute exercise were determined at the end of each training week. Self-reported
      symptoms of upper-respiratory tract infections (URTI) were monitored daily by
      questionnaire. Undertaking high-intensity training with a high protein diet
      restored leukocyte kinetics to similar levels observed during normal-intensity
      training: CD8(+) TL mobilization (normal-intensity: 29,319+/
      13,130cells/MUL*~165min vs. high-intensity with protein: 26,031+/
      17,474cells/MUL*~165min, P>0.05), CD8(+) TL egress (normal-intensity: 624+/
      264cells/MUL vs. high-intensity with protein: 597+/-478cells/MUL, P>0.05). This
      pattern was driven by effector-memory populations mobilizing (normal-intensity:
      6,145+/-6,227cells/MUL*~165min vs. high-intensity with protein: 6,783+/
      8,203cells/MUL*~165min, P>0.05) and extravastating from blood (normal-intensity:
      147+/-129cells/MUL vs. high-intensity with protein: 165+/-192cells/MUL, P>0.05).
      High-intensity training while consuming a high protein diet was associated with
      fewer symptoms of URTI compared to performing high-intensity training with a
      normal diet (P<0.05). To conclude, a high protein diet might reduce the incidence
      of URTI in athletes potentially mediated by preventing training-induced
      impairments in immune-surveillance. 

PMID- 24120934
TI  - A new approach to measuring phosphoinositides in cells by mass spectrometry.
AB  - The phosphoinositide family of phospholipids, defined here as PtdIns, PtdIns3P,
      PtdIns4P, PtdIns5P, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns(4,5)P2 and
      PtdIns(3,4,5)P3, play pivotal roles in organising the location and activity of
      many different proteins acting on biological membranes, including those involved
      in vesicle and protein trafficking through the endolysosomal system and receptor
      signal transduction at the plasma membrane. Accurate measurement of the cellular
      levels of these lipids, particularly the more highly phosphorylated species, is
      hampered by their high polarity and low cellular concentrations. Recently, much
      progress has been made in using mass spectrometry to measure many different lipid
      classes in parallel, an approach generally referred to as 'lipidomics'.
      Unfortunately, the acidic nature of highly phosphorylated phosphoinositides makes
      them difficult to measure using these methods, because they yield low levels of
      useful ions; this is particularly the case with PtdIns(3,4,5)P3. We have solved
      some of these problems by methylating the phosphate groups of these lipids with
      TMS-diazomethane and describe a simple, integrated approach to measuring PtdIns,
      PtdInsP, PtdInsP2 and PtdInsP3 classes of lipids, in parallel with other
      phospholipid species, in cell and tissue extracts. This methodology is sensitive,
      accurate and robust, and also yields fatty-acyl compositions, suggesting it can
      be used to further our understanding of both the normal and pathophysiological
      roles of these important lipids. 

PMID- 24120933
TI  - NET-Works: Linking families, communities and primary care to prevent obesity in
      preschool-age children.
AB  - Obesity prevention in children offers a unique window of opportunity to establish
      healthful eating and physical activity behaviors to maintain a healthful body
      weight and avoid the adverse proximal and distal long-term health consequences of
      obesity. Given that obesity is the result of a complex interaction between
      biological, behavioral, family-based, and community environmental factors,
      intervention at multiple levels and across multiple settings is critical for both
      short- and long-term effectiveness. The Minnesota NET-Works (Now Everybody
      Together for Amazing and Healthful Kids) study is one of four obesity prevention
      and/or treatment trials that are part of the Childhood Obesity Prevention and
      Treatment (COPTR) Consortium. The goal of the NET-Works study is to evaluate an
      intervention that integrates home, community, primary care and neighborhood
      strategies to promote healthful eating, activity patterns, and body weight among
      low income, racially/ethnically diverse preschool-age children. Critical to the
      success of this intervention is the creation of linkages among the settings to
      support parents in making home environment and parenting behavior changes to
      foster healthful child growth. Five hundred racially/ethnically diverse, two-four
      year old children and their parent or primary caregiver will be randomized to the
      multi-component intervention or to a usual care comparison group for a three-year
      period. This paper describes the study design, measurement and intervention
      protocols, and statistical analysis plan for the NET-Works trial. 

PMID- 24120935
TI  - Phenotypic modulation and cytokine profiles of antigen presenting cells by
      European subtype 1 and 3 porcine reproductive and respiratory syndrome virus
      strains in vitro and in vivo.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes continuous
      problems in the pig industry, due to high costs of outbreaks and reduced welfare
      of diseased pigs. The severity of infection is, partly, dependent on the virus
      strain. Recently isolated Eastern-European subtype 3 strains are more pathogenic
      than the widespread subtype 1 strains. There is, however, almost no information
      available about the mechanisms involved in the pathogenicity of these subtype 3
      strains. The objective of the present study was to characterize the in vitro and
      in vivo response of two European subtype 1 strains, Belgium A and Lelystad-Ter
      Huurne (LV), and a virulent subtype 3 strain, Lena, in bone marrow-derived
      dendritic cells (BM-DC) (in vitro) and alveolar macrophages (in vitro and in
      vivo). It was shown that infection with the Lena strain resulted in a higher
      apoptosis of cells in vitro and a higher level of infectivity in vitro and in
      vivo than the other virus strains. Furthermore, infection with Lena resulted in a
      small downregulation of the immunologically relevant cell surface molecules SLA
      I, SLA-II and CD80/86 in vitro, and SLA-II in vivo. In spite of these
      differences, in vitro cytokine responses did not differ significantly between
      strains, except for the absence of IL-10 production by Lena in BM-DC. The higher
      infectivity, apoptosis and downregulation of the cell surface molecules, may have
      contributed to the increased pathogenicity of Lena, and have dampened specific
      immune responses. This could explain the delayed and decreased adaptive immune
      responses observed after infections with this strain. 

PMID- 24120936
TI  - Pathogenicity in domestic ducks and mice of highly pathogenic H5N1 clade 2.3.2.1
      influenza viruses recently circulating in Eastern Asia.
AB  - Influenza virus A (H5N1) clade 2.3.2.1 has recently caused widespread outbreaks
      of disease in domestic poultry and wild birds in Eastern Asia. In the current
      study, the antigenicity and pathogenicity of three clade 2.3.2.1 viruses
      (Ck/Kr/Gimje/08, Ws/Mongolia/1/09, and Ws/Mongolia/7/10) were investigated in
      domestic ducks and mice. The H5N1 influenza viruses in this study were
      antigenically similar to each other (r-values of 0.35-1.4). The three viruses
      replicated systemically in all tissues tested in domestic ducks, indicating high
      pathogenicity. However, the viruses produced different clinical signs and
      mortality rates: Ck/Kr/Gimje/08 and Ws/Mongolia/1/09 resulted in 100% mortality
      with severe neurological signs, whereas Ws/Mongolia/7/10 resulted in 50%
      mortality with relatively mild neurological signs. In mice, infection with
      Ck/Kr/Gimje/08 and Ws/Mongolia/7/10 resulted in weight loss that peaked at 4 days
      post-infection (22.3% and 20.8%, respectively), same MLD50 (2.2 Log10 EID50) and
      systemic replication. The three viruses had K deletion at the -2 position of the
      HA1-connecting peptide (PQRERRRK-R), which is associated with increased virulence
      in domestic ducks and harbored NA stalk deletion, NS1 deletion and mutation of
      P42S in NS1, and full length (90aa) in PB1-F2, which confer increased virulence
      in mice. Our study shows that clade 2.3.2.1 viruses from Korea and Mongolia are
      antigenically similar and highly pathogenic in both domestic ducks and mice.
      Moreover, we provide molecular determinants of the clade 2.3.2.1 viruses
      associated with the pathogenicity in domestic ducks and mice, respectively. 

PMID- 24120937
TI  - A simple atomic-level hydrophobicity scale reveals protein interfacial structure.
AB  - Many amino acid residue hydrophobicity scales have been created in an effort to
      better understand and rapidly characterize water-protein interactions based only
      on protein structure and sequence. There is surprisingly low consistency in the
      ranking of residue hydrophobicity between scales, and their ability to provide
      insightful characterization varies substantially across subject proteins. All
      current scales characterize hydrophobicity based on entire amino acid residue
      units. We introduce a simple binary but atomic-level hydrophobicity scale that
      allows for the classification of polar and non-polar moieties within single
      residues, including backbone atoms. This simple scale is first shown to capture
      the anticipated hydrophobic character for those whole residues that align in
      classification among most scales. Examination of a set of protein binding
      interfaces establishes good agreement between residue-based and atomic-level
      descriptions of hydrophobicity for five residues, while the remaining residues
      produce discrepancies. We then show that the atomistic scale properly classifies
      the hydrophobicity of functionally important regions where residue-based scales
      fail. To illustrate the utility of the new approach, we show that the atomic
      level scale rationalizes the hydration of two hydrophobic pockets and the
      presence of a void in a third pocket within a single protein and that it
      appropriately classifies all of the functionally important hydrophilic sites
      within two otherwise hydrophobic pores. We suggest that an atomic level of detail
      is, in general, necessary for the reliable depiction of hydrophobicity for all
      protein surfaces. The present formulation can be implemented simply in a manner
      no more complex than current residue-based approaches. 

PMID- 24120938
TI  - Structure of a prokaryotic sodium channel pore reveals essential gating elements
      and an outer ion binding site common to eukaryotic channels.
AB  - Voltage-gated sodium channels (NaVs) are central elements of cellular excitation.
      Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key
      questions about gating and ion selectivity remain. Here, we present a closed
      conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from
      the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California,
      that provides insight into both fundamental properties. The structure reveals a
      pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic
      tail. Electrophysiological studies of full-length BacNaVs show that two elements
      defined by the NaVAe1p structure, an S6 activation gate position and the
      cytoplasmic tail "neck", are central to BacNaV gating. The structure also reveals
      the selectivity filter ion entry site, termed the "outer ion" site. Comparison
      with mammalian voltage-gated calcium channel (CaV) selectivity filters, together
      with functional studies, shows that this site forms a previously unknown
      determinant of CaV high-affinity calcium binding. Our findings underscore
      commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a
      framework for understanding gating and ion permeation in this superfamily. 

PMID- 24120939
TI  - Structural and functional analysis of human SIRT1.
AB  - SIRT1 is a NAD(+)-dependent deacetylase that plays important roles in many
      cellular processes. SIRT1 activity is uniquely controlled by a C-terminal
      regulatory segment (CTR). Here we present crystal structures of the catalytic
      domain of human SIRT1 in complex with the CTR in an open apo form and a closed
      conformation in complex with a cofactor and a pseudo-substrate peptide. The
      catalytic domain adopts the canonical sirtuin fold. The CTR forms a beta hairpin
      structure that complements the beta sheet of the NAD(+)-binding domain, covering
      an essentially invariant hydrophobic surface. The apo form adopts a distinct open
      conformation, in which the smaller subdomain of SIRT1 undergoes a rotation with
      respect to the larger NAD(+)-binding subdomain. A biochemical analysis identifies
      key residues in the active site, an inhibitory role for the CTR, and distinct
      structural features of the CTR that mediate binding and inhibition of the SIRT1
      catalytic domain. 

PMID- 24120940
TI  - Serum-dependent enhancement of coxsackievirus B4-induced production of IFNalpha,
      IL-6 and TNFalpha by peripheral blood mononuclear cells.
AB  - Only a few reports have been published on the interactions between Coxsackievirus
      B4 (CVB4) and human peripheral blood mononuclear cells (PBMC) but have not been
      extensively documented. Human serum containing non-neutralizing anti-CVB4
      antibodies increased CVB4-induced synthesis of IFNalpha by PBMC. In this study,
      we determined if CVB4 and human serum have the ability to activate inflammatory
      cytokines in addition to IFNalpha in PBMC cultures. PBMC from healthy donors were
      inoculated with infectious, inactivated CVB4 or with CVB4 incubated with
      dilutions of human serum or polyvalent IgG with anti-CVB4 activity. Levels of
      IFNalpha, TNFalpha, IL-6, IL-12, IFNgamma and IL-10 in the cell-free supernatants
      of PBMC cultures were measured using ELISA. Infection was assessed by real-time
      PCR. PBMC inoculated with CVB4 produced inflammatory cytokines but not IFNalpha.
      When CVB4 was incubated with serum or IgG, IFNalpha was detected in the culture
      supernatants, and high concentrations of TNFalpha and IL-6 were measured. The
      concentrations of TNFalpha and IL-6 were not reduced in cultures inoculated with
      inactivated CVB4, whereas the IgG-dependent enhancement of IFNalpha, IL-6 and
      TNFalpha production with inactivated virus was suppressed. The potentiation of
      IFNalpha production was associated with a high intracellular viral load.
      Infectious and non-infectious CVB4 can induce the production of inflammatory
      cytokines but not IFNalpha by PBMC. High levels of IFNalpha, in addition to
      TNFalpha and IL-6, in culture supernatants were obtained when infectious CVB4 was
      combined with immune serum or IgG, and they were associated with high amounts of
      intracellular viral RNA. 

PMID- 24120941
TI  - The cytoplasmic domain of the T-cell receptor zeta subunit does not form
      disordered dimers.
AB  - Intrinsically disordered regions in proteins play active roles in recognition,
      signaling and molecular sorting. They often undergo coupled folding and binding
      giving rise to largely ordered interfaces with their binding partners. The
      cytoplasmic region of the T-cell receptor zeta subunit (zetacyt) has been
      previously proposed to specifically dimerize in the absence of a disorder-to
      order transition, suggesting an intriguing dimerization mechanism that may
      involve multiple transient interfaces. We show here using analytical
      ultracentrifugation, NMR, size-exclusion chromatography (SEC) and multi-angle
      light scattering that neither zetacyt nor the cytoplasmic region of CD3epsilon
      significantly populates a dimeric state but that they are mostly monomers in
      solution up to millimolar concentrations. They experience a salt- and
      concentration-dependent shift of their elution volume in SEC previously
      interpreted as dimerization. Our data show that zetacyt does not form a highly
      disordered protein complex and leaves open the question as to whether completely
      disordered dimers (or other oligomers) exist in nature. 

PMID- 24120942
TI  - An integrated serotonin and octopamine neuronal circuit directs the release of an
      endocrine signal to control C. elegans body fat.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is an ancient and conserved neuromodulator
      of energy balance. Despite its importance, the neural circuits and molecular
      mechanisms underlying 5-HT-mediated control of body fat remain poorly understood.
      Here, we decipher the serotonergic neural circuit for body fat loss in C. elegans
      and show that the effects of 5-HT require signaling from octopamine, the
      invertebrate analog of adrenaline, to sustain body fat loss. Our results provide
      a potential molecular explanation for the long-observed potent effects of
      combined serotonergic and adrenergic weight loss drugs. In metabolic tissues, we
      find that the conserved regulatory adipocyte triglyceride lipase ATGL-1 drives
      serotonergic fat loss. We show that the serotonergic chloride channel MOD-1
      relays a long-range endocrine signal from C. elegans body cavity neurons to
      control distal ATGL-1 function, via the nuclear receptor NHR-76. Our findings
      establish a conserved neuroendocrine axis operated by neural serotonergic and
      adrenergic-like signaling to regulate body fat.

PMID- 24120943
TI  - Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway.
AB  - Exercise can improve cognitive function and has been linked to the increased
      expression of brain-derived neurotrophic factor (BDNF). However, the underlying
      molecular mechanisms driving the elevation of this neurotrophin remain unknown.
      Here we show that FNDC5, a previously identified muscle protein that is induced
      in exercise and is cleaved and secreted as irisin, is also elevated by endurance
      exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated
      by PGC-1alpha, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain.
      Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression,
      whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral
      delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated
      blood irisin, induces expression of Bdnf and other neuroprotective genes in the
      hippocampus. Taken together, our findings link endurance exercise and the
      important metabolic mediators, PGC-1alpha and FNDC5, with BDNF expression in the
      brain.

PMID- 24120945
TI  - Dehydroepiandrosterone-sulfate (DHEAS) promotes MIN6 cells insulin secretion via
      inhibition of AMP-activated protein kinase.
AB  - Derived from adrenal cortical, dehydroepiandrosterone-sulfate (DHEAS) is a
      precursor to androgens and estrogens, with various bioactivities. Although it has
      the property of anti-diabetes, the long-term effect of DHEAS on insulin secretion
      in beta-cells is still unclear. In this study, the effect of DHEAS on the insulin
      secretion activity in MIN6 cell lines in vitro was assessed. Insulin biosynthesis
      and secretion were stimulated by DHEAS for 24h. DHEAS inhibited the AMPK
      activation and upregulated the expression of ACC-1. These findings indicate that
      DHEAS may exert prominent stimulatory effects on insulin secretion partly via
      AMPK inhibition and ACC-1 upregulation. 

PMID- 24120944
TI  - Inhibitory effect of Nodal on the expression of aldehyde dehydrogenase 1 in
      endometrioid adenocarcinoma of uterus.
AB  - Cancers consist of heterogeneous populations. Recently, it has been demonstrated
      that cells with tumorigenic potential are limited to a small population, called
      cancer-initiating cells (CICs). Aldehyde dehydrogenase 1 (ALDH1) is one of the
      markers of CICs. We previously reported that ALDH1-high cases of uterine
      endometrioid adenocarcinoma showed poor prognosis, and ALDH1-high population of
      endometrioid adenocarcinoma cell line was more tumorigenic, resistant to anti
      cancer drugs, and invasive than ALDH1-low population. Here, the regulatory
      signaling for ALDH1 was examined. The inhibition of TGF-beta signaling increased
      ALDH1-high population. Among TGF-beta family members, Nodal expression and ALDH1
      expression levels were mutually exclusive. Immunohistochemical analysis on
      clinical samples revealed Nodal-high tumor cells to be ALDH-low and vise versa,
      suggesting that Nodal may inhibit ALDH1 expression via stimulating TGF-beta
      signaling in uterine endometrioid adenocarcinoma. In fact, the addition of Nodal
      to endometrioid adenocarcinoma cell line reduced ALDH1-high population. Although
      ALDH1 mRNA level was not affected, the amount of ALDH1 protein appeared to be
      reduce by Nodal through ubiquitine-proteasome pathway. The regulation of TGF-beta
      signaling might be a novel therapeutic target of CICs in endometrioid
      adenocarcinoma. 

PMID- 24120946
TI  - Nucleoredoxin regulates glucose metabolism via phosphofructokinase 1.
AB  - Phosphofructokinase (PFK) 1 is a glycolytic enzyme, and its abnormality
      contributes to the development of multiple human diseases, such as cancer. Here,
      we report that nucleoredoxin (NRX), a thioredoxin-related oxidoreductase, is a
      novel interacting partner of PFK1. NRX binds directly to PFK1, and endogenous NRX
      and PFK1 interact in vivo. In NRX(-/-) mouse embryonic fibroblasts (MEFs), the
      oligomerization status of PFK1 is altered and the catalytic activity of PFK1 is
      decreased. NRX deficiency augmented levels of NADPH and reduced glutathione, two
      major cellular antioxidants generated through the pentose phosphate pathway.
      Indeed, NRX(-/-) MEFs are significantly more resistant to oxidative stress than
      NRX(+/+) MEFs. These results reveal a novel role of NRX in the regulation of PFK1
      activity and in the balance between glycolysis and the pentose phosphate pathway.

PMID- 24120947
TI  - Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine values determined by a modified ELISA
      improves agreement with HPLC-MS/MS.
AB  - ELISA is widely used for urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
      analysis. It is the method of choice for laboratories that lack specialized
      chromatographic instrumentation. It allows fast, high-throughput sample analysis
      without a need for extensive samples processing. However, a lack of agreement
      between ELISA and chromatographic methods confines its application to the
      assessment of relative urinary 8-oxodG levels. We investigated various ELISA
      modifications, seeking optimal conditions that would yield a good agreement
      between ELISA and high-performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS /MS). Purification of urine by solid phase extraction (SPE), then
      incubation with the anti-8-oxodG antibody at 4  degrees C overnight and
      subsequent normalization of 8-oxodG levels per urinary creatinine resulted in a
      near-perfect correlation and agreement in mean levels between ELISA and HPLC-MS
      /MS (r=0.917, p<0.001; and paired t-test p=0.803, respectively). Our data show
      that, after introduction of a simple modification, ELISA quantification urinary 8
      oxodG substantially improves. Although more sample manipulation is required, the
      method retains its key advantages over chromatography (high-throughput analysis
      that does not require expensive instrumentation). This represents a significant
      advance for the ELISA, and encouraging its use in more studies adding to our
      knowledge of the role of this biomarker of oxidative stress in health and
      disease.

PMID- 24120948
TI  - MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma.
AB  - Retinoblastoma is the most common pediatric cancer of the eye. Currently, the
      chemotherapeutic treatments for retinoblastoma are broad-based drugs such as
      vincristine, carboplatin, or etoposide. However, therapies targeted directly to
      aberrant signaling pathways may provide more effective therapy for this disease.
      The purpose of our study is to illustrate the relationship between the
      expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis.
      We are the first to confirm an inhibitory effect of miR-449a and -449b in
      retinoblastoma by demonstrating significantly impaired proliferation and
      increased apoptosis of tumor cells when these miRNAs are overexpressed. This
      study suggests that these miRNAs could serve as viable therapeutic targets for
      retinoblastoma treatment. 

PMID- 24120949
TI  - New insights into the catalytic mechanism of Bombyx mori prostaglandin E synthase
      gained from structure-function analysis.
AB  - Prostaglandin E synthase (PGES) catalyzes the isomerization of PGH2 to PGE2. We
      previously reported the identification and structural characterization of Bombyx
      mori PGES (bmPGES), which belongs to Sigma-class glutathione transferase. Here,
      we extend these studies by determining the structure of bmPGES in complex with
      glutathione sulfonic acid (GTS) at a resolution of 1.37 A using X-ray
      crystallography. GTS localized to the glutathione-binding site. We found that
      electron-sharing network of bmPGES includes Asn95, Asp96, and Arg98. Site
      directed mutagenesis of these residues to create mutant forms of bmPGES mutants
      indicate that they contribute to catalytic activity. These results are, to our
      knowledge, the first to reveal the presence of an electron-sharing network in
      bmPGES.

PMID- 24120950
TI  - Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate
      (MEHP)-induced Sertoli cell injury: probably an indirect action via the
      regulation of NFkappaB/FasL circuitry.
AB  - The Fas/FasL signaling pathway, controlled by nuclear factor-kappaB (NFkappaB) at
      the transcriptional level, is critical for triggering germ cell apoptosis in
      response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC)
      injury, but the exact regulation mechanism remain unknown. Here, we discovered
      that expression level of Metastasis associated protein 1 (MTA1), a component of
      the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs
      during the early recovery after MEHP exposure. This expression change was in line
      with the dynamic changes in germ cell apoptosis in response to MEHP treatment.
      Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP
      induced early activation of NFkappaB pathway and abolish the recruitment of
      NFkappaB onto FasL promoter, which consequently diminished the MEHP-triggered
      FasL induction. Considering that Fas/FasL is a well characterized apoptosis
      initiating signaling during SCs injury, our results point to a potential "switch
      on" effect of MTA1, which may govern the activation of NFkappaB/FasL cascade in
      MEHP-insulted SCs. Overall, the MTA1/NFkappaB/FasL circuit may serve as an
      important defensive/repairing mechanism to help to control the germ cell quality
      after SCs injury. 

PMID- 24120952
TI  - Immediate vs. delayed treatment of psychogenic movement disorders with short term
      psychodynamic psychotherapy: randomized clinical trial.
AB  - OBJECTIVE: In subjects with psychogenic movement disorders (PMDs), we conducted a
      6 month randomized, cross-over design study to assess the effect of 3 months of
      psychodynamic psychotherapy followed by observation by the neurologist vs.
      observation by the neurologist, then 3 months of psychiatric intervention.
      BACKGROUND: PMDs are often disabling but no uniformly successful treatment
      strategies have been identified. Short term, open label psychodynamic
      psychotherapy has been successful in improving PMDs but whether PMDs improve
      equally well with neurological observation and support has not been tested.
      DESIGN: Fifteen patients with PMDs were randomized to immediate vs. delayed
      (after 3 months) weekly psychodynamic psychotherapy for 12 weeks. During the
      phase without psychiatric intervention, they were monitored by the treating
      neurologist. Patients were assessed at baseline, 3 and 6 months. Change in their
      movement disorder was assessed using a clinical global impression scale change
      (CGI-c), depression and anxiety using the Hamilton Depression Scale (HAM-D) and
      Beck Anxiety Inventory (Beck-A). RESULTS: Fourteen women and one man, age 42.3 +/
      11, disease duration 63.2 +/- 73 months, were randomized to immediate (7
      patients) or delayed (8 patients) treatment. Over the six month study, PMDs,
      depression and anxiety were significantly improved but time was the determinant
      factor without an independent effect of treatment assignment. CONCLUSION: In this
      group of PMD patients, where patients were kept within the medical system and
      involved in a research program, PMDs as well as depression and anxiety improved,
      but without specific benefit time-linked to psychotherapy as opposed to
      neurological observation and support.

PMID- 24120951
TI  - Dietary fat intake, pesticide use, and Parkinson's disease.
AB  - BACKGROUND: Dietary fat intake may modify Parkinson's disease (PD) risk directly
      or by altering the response to environmental neurotoxicants including pesticides.
      METHODS: We conducted a case-control study of PD nested in the Agricultural
      Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated
      diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement
      disorder specialists, or a corresponding date in 336 frequency-matched controls.
      Associations were evaluated using multivariate logistic regression to estimate
      odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In the AHS, PD was
      inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI
      0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor alpha-linolenic
      acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present
      one, PD was inversely associated with alpha-linolenic acid (0.81, 0.68-0.96). In
      the AHS, associations of PD with the pesticides paraquat and rotenone were
      modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with
      PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p
      interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated
      fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p
      interaction = 0.02). CONCLUSIONS: PUFA intake was consistently associated with
      lower PD risk, and dietary fats modified the association of PD risk with
      pesticide exposure. If confirmed, these findings suggest that a diet high in
      PUFAs and low in saturated fats might reduce risk of PD.

PMID- 24120953
TI  - Combination of vaniprevir with peginterferon and ribavirin significantly
      increases the rate of SVR in treatment-experienced patients with chronic HCV
      genotype 1 infection and cirrhosis.
AB  - BACKGROUND & AIMS: The combination of vaniprevir (a NS3/4A protease inhibitor)
      with peginterferon and ribavirin was shown to increase rates of sustained
      virologic response (SVR) significantly, compared with peginterferon and ribavirin
      alone, in treatment-experienced patients with chronic hepatitis C virus (HCV)
      genotype 1 infection without cirrhosis. We performed a blinded, randomized,
      controlled trial of the effects of vaniprevir with peginterferon and ribavirin in
      patients with cirrhosis who did not respond to prior therapy with peginterferon
      and ribavirin. METHODS: Treatment-experienced patients (88% white and 35% prior
      null responders) with HCV genotype 1 infection and compensated cirrhosis were
      assigned randomly to groups given vaniprevir (600 mg twice daily) with
      peginterferon and ribavirin for 24 weeks (n = 16), vaniprevir (600 mg twice
      daily) for 24 weeks with peginterferon and ribavirin for 48 weeks (n = 14),
      vaniprevir (300 mg twice daily) with peginterferon and ribavirin for 48 weeks (n
      = 15), vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 48
      weeks (n = 15), or placebo with peginterferon and ribavirin for 48 weeks (n = 14,
      control). Cirrhosis was documented by liver biopsy (84%) or noninvasive methods
      (16%). Before randomization, participants were stratified based on their
      historical response to peginterferon and ribavirin. RESULTS: In the primary
      analysis, SVR rates among patients in the respective vaniprevir groups were 9 of
      15 (60.0%), 9 of 13 (69.2%), 8 of 15 (53.3%), and 10 of 13 (76.9%), compared with
      2 of 14 (14.3%) in the control group (pairwise P values <= .016). Cirrhotic
      patients with null or partial responses to prior therapy achieved SVR less often
      than patients with prior breakthrough or relapse, although 42.1% of prior null
      responders in the vaniprevir groups achieved SVRs. Patients in the vaniprevir
      groups more frequently experienced mild-moderate nausea, vomiting, and diarrhea
      than controls; 5% developed grade 2 anemia compared with none in the control
      group (no patient developed grade 3 or 4 anemia). Among patients in the
      vaniprevir groups who experienced virologic failure, resistance-associated
      variants were detected predominantly at positions 155, 156, and 168 in the HCV
      protease gene. CONCLUSIONS: In a controlled phase 2B trial, vaniprevir with
      peginterferon and ribavirin significantly increased rates of SVR among treatment
      experienced patients with chronic HCV genotype 1 infection, compared with re
      treatment with peginterferon and ribavirin alone. Vaniprevir generally was well
      tolerated for up to 48 weeks in patients with compensated cirrhosis.
      ClinicalTrials.gov number, NCT00704405.

PMID- 24120955
TI  - International Journal of Food Microbiology. Preface.

PMID- 24120954
TI  - Multidrug resistance: Physiological principles and nanomedical solutions.
AB  - Multidrug resistance (MDR) is a pathophysiological phenomenon employed by cancer
      cells which limits the prolonged and effective use of chemotherapeutic agents.
      MDR is primarily based on the over-expression of drug efflux pumps in the
      cellular membrane. Prominent examples of such efflux pumps, which belong to the
      ATP-binding cassette (ABC) superfamily of proteins, are Pgp (P-glycoprotein) and
      MRP (multidrug resistance-associated protein), nowadays officially known as ABCB1
      and ABCC1. Over the years, several strategies have been evaluated to overcome
      MDR, based not only on the use of low-molecular-weight MDR modulators, but also
      on the implementation of 1-100(0) nm-sized drug delivery systems. In the present
      manuscript, after introducing the most important physiological principles of MDR,
      we summarize prototypic nanomedical strategies to overcome multidrug resistance,
      including the use of carrier materials with intrinsic anti-MDR properties, the
      use of nanomedicines to modify the mode of cellular uptake, and the co
      formulation of chemotherapeutic drugs together with low- and high-molecular
      weight MDR inhibitors within a single drug delivery system. While certain
      challenges still need to be overcome before such constructs and concepts can be
      widely applied in the clinic, the insights obtained and the progress made
      strongly suggest that nanomedicine formulations hold significant potential for
      improving the treatment of multidrug-resistant malignancies.

PMID- 24120956
TI  - Purification, characterization and immunomodulating activity of a pectic
      polysaccharide isolated from Korean mulberry fruit Oddi (Morus alba L.).
AB  - A water-soluble polysaccharide (JS-MP-1) was isolated and purified from the
      Korean mulberry fruits Oddi (Morus alba L.) by crushing the fresh fruits then
      performing ethanol precipitation and DEAE-cellulose ion exchange chromatography.
      The neutral monosaccharide composition of the purified JS-MP-1 was determined to
      be composed mainly of galactose (37.6%, in mole percent), arabinose (36.3%), and
      rhamnose (18.4%), while other major sugars such as glucose, xylose, mannose, and
      fucose were present as minor components. HPLC analysis revealed that JS-MP-1
      contains both galacturonic acid (GalA) and glucuronic acid (GlcA) at
      approximately 4:1 in mole percent. Monosaccharide composition, Fourier-transform
      infrared (FTIR) analysis, biochemical analysis, and elemental analysis suggested
      that JS-MP-1 is an acidic heteropolysaccharide, most likely a
      rhamnoarabinogalacturonan type plant pectic polysaccharide, with an apparent
      molecular mass of 1600 kDa containing no, or if any, negligible level of sulfate
      esters and proteins. Enzyme-Linked Immunosorbent Assay and RT-PCR analysis
      demonstrated that JS-MP-1 significantly stimulates murine RAW264.7 macrophage
      cells to release chemokines (RANTES and MIP-1alpha) and proinflammatory cytokines
      (TNF-alpha and IL-6) and to induce the expression of iNOS and COX-2, which are
      responsible for the production of NO and prostaglandin PGE2, respectively. These
      results suggest that the mulberry fruit-derived polysaccharide JS-MP-1 can act as
      a potent immunomodulator, and these observations may support the applicability of
      this polysaccharide as an immunotherapeutic adjuvant or the water extracts of the
      mulberry fruit as a beneficial health food.

PMID- 24120958
TI  - Cortical thickness in first-episode schizophrenia patients and individuals at
      high familial risk: a cross-sectional comparison.
AB  - BACKGROUND: Schizophrenia is associated with cortical thickness reductions in the
      brain, but it is unclear whether these are present before illness onset, and to
      what extent they are driven by genetic factors. METHODS: In the Edinburgh High
      Risk Study, structural MRI scans of 150 young individuals at high familial risk
      for schizophrenia, 34 patients with first-episode schizophrenia and 36 matched
      controls were acquired, and clinical information was collected for the following
      10 years for the high-risk and control group. During this time, 17 high-risk
      individuals developed schizophrenia, on average 2.5 years after the scan, and 57
      experienced isolated or sub-clinical psychotic symptoms. We applied surface-based
      analysis of the cerebral cortex to this cohort, and extracted cortical thickness
      in automatically parcellated regions. RESULTS: Analysis of variance revealed
      widespread thinning of the cerebral cortex in first-episode patients, most
      pronounced in superior frontal, medial parietal, and lateral occipital regions
      (corrected p<10(-4)). In contrast, cortical thickness reductions were only found
      in high-risk individuals in the left middle temporal gyrus (corrected p<0.05).
      There were no significant differences between those at high risk who later
      developed schizophrenia and those who remained well. CONCLUSIONS: These findings
      confirm cortical thickness reductions in schizophrenia patients. Increased
      familial risk for schizophrenia is associated with thinning in the left middle
      temporal lobe, irrespective of subsequent disease onset. The absence of
      widespread cortical thinning before disease onset implies that the cortical
      thinning is unlikely to simply reflect genetic liability to schizophrenia but is
      predominantly driven by disease-associated factors.

PMID- 24120957
TI  - Post-transplant repopulation of naive and memory T cells in blood and lymphoid
      tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus
      monkeys.
AB  - Repopulation of memory T cells (Tmem) in allograft recipients after
      lymphodepletion is a major barrier to transplant tolerance induction. Ineffective
      depletion of naive T cells (Tn) and Tmem may predispose to repopulation of Tmem
      after transplantation. Cynomolgus macaque monkeys given heart allografts were
      lymphodepleted using Alemtuzumab (Campath-1H; anti-CD52). Peripheral blood (PB)
      and lymph nodes (LN) were analyzed for CD95(-) (Tn) and CD95(+) cells (Tmem), one
      day, one month and up to three months after Alemtuzumab infusion. CD52
      expression, susceptibility to Alemtuzumab cytotoxicity and pro-apoptotic caspase
      3 were evaluated in Tn and Tmem. In vivo, Alemtuzumab induction profoundly
      depleted lymphocytes in PB (99% reduction) but exerted a lesser effect in LN (70%
      reduction), with similar depletion of Tn and Tmem subsets. After transplantation,
      Tmem comprised the majority of lymphocytes in PB and LN. In vitro, LN T cells
      were more resistant to Alemtuzumab-mediated cytotoxicity than PB lymphocytes.
      CD4(+) Tn and Tmem were equally susceptible to Alemtuzumab-mediated cytotoxicity,
      whereas CD8(+) Tn were more resistant than CD8(+) Tmem. However, no significant
      differences in CD52 expression between lymphocyte subsets in PB and LN were
      observed. Caspase-3 expression was higher in PB than LN T cells. CD4(+) and
      CD8(+) Tn expressed lower levels of Caspase-3 than Tmem, in both PB and LN. Thus,
      after Alemtuzumab infusion, residual Tn in secondary lymphoid tissue may
      predispose to rapid recovery of Tmem in allograft recipients. 

PMID- 24120961
TI  - Methotrexate-loaded chitosan nanogels as 'Trojan Horses' for drug delivery to
      brain: preparation and in vitro/in vivo characterization.
AB  - Methotrexate-loaded hydrogel nanoparticles were prepared and after in vitro
      characterization, their transport across blood-brain barrier was investigated in
      vivo in intact animals in this study. The ionic gelation method was used for
      preparation of drug-loaded nanogels, after optimized by a systematic multi
      objective optimization approach. After surface-modification with polysorbate 80,
      nanoparticles with the final particle size, poly-dispersity index (PDI), loading
      efficiency (LE) and loading capacity (LC) of 118.54 +/- 15.93 nm, 0.35 +/- 0.05,
      61.82 +/- 6.84%, and 53.68 +/- 3.09% were obtained, respectively. The in vitro
      drug release study indicated non-Fickian diffusion kinetic, apparently governed
      by both diffusion of the drug out of the nanoparticles and
      swelling/disintegration of the polymeric network as characterized by a Weibull
      model for both surface-treated and untreated nanogels. After intravenous
      administration of surface-modified and unmodified nanogels compared to the free
      drug, all with the same dose of 25 mg/kg, remarkably higher brain concentrations
      of methotrexate were achieved with the nanogel formulations in comparison to the
      free drug (in some cases, more than 10-fold); but there were no significant
      differences between the surface-modified and unmodified nanogels in all the time
      points tested.

PMID- 24120960
TI  - Synthesis, antimicrobial and release of chloroamphenicol loaded poly(L-lactic
      acid)/ZrO2 nanofibrous membranes.
AB  - Electrospinning technique was used to fabricate chloroamphenicol loaded poly (L
      lactic acid)/ZrO2 (CP-PLLA/ZrO2) nanofibrous membranes. The average diameter of
      drug carrier PLLA/ZrO2 nanofibers increased with ZrO2 concentration increasing
      and ribbon-shape fibers were present when ZrO2 content reached 3% and above. The
      existence of hydrogen and ZrOC bonds between PLLA and ZrO2 units improved the
      thermal stability of PLLA. The model drug CP loading showed no significant
      changes on the size and shape of nanofibers when CP content was below 8%, but the
      fibers were uneven and interspersed with ball-shape beads when CP content rose up
      to 10%. From the antimicrobial activity and release experimental result, the CP
      PLLA/ZrO2 nanofibrous membranes revealed well controlled release and better
      antimicrobial activity against Staphylococcus aureus, which may have potential as
      a new nanofibrous membrane in drug delivery and wound dressing.

PMID- 24120962
TI  - Regioselective synthesis of sulfated guar gum: comparative studies of structure
      and antioxidant activities.
AB  - We reported here a new synthesis of C-2 and C-3 sulfated guar gum (SRSGG) with
      low degree of substitution (DSS) of 0.58, employing triphenylchloromethane (TrCl)
      as a protected precursor. The yield and DSTr (calculated from the weight of
      triphenylmethanol) of triphenylmethylated GG (GGTr) was 165.6% and 0.71,
      respectively. In addition, low ratio (1:4) of chlorosulfuric acid to pyridine
      (1:4) was chosen in sulfation reaction since the protecting group was slightly
      sensitive to acid. Results of FT-IR and (13)C NMR spectroscopy indicated that C-2
      and C-3 substitution was predominant but not fully sulfated in SRSGG. Size
      exclusion chromatograph combined with multi-angle laser photometer (SEC-LLS)
      showed a decrease in molecular weight in the reaction. This might be due to the
      degradation in sulfation and deprotection process. Finally, we investigated the
      effect of structure features on the antioxidant activities in vitro. Vitro
      antioxidant experiments revealed that the regioselective sulfation at C-2 and C-3
      and low molecular weight afforded strong antioxidant activities showing a much
      higher scavenging abilities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl
      radical than that by the known C-6-sulfated derivative. The antioxidant
      activities of sulfated polysaccharides were not a function of a single factor but
      a combination of molecular weight, DSS and substitution positions.

PMID- 24120963
TI  - Chitin based polyurethanes using hydroxyl terminated polybutadiene, part III:
      surface characteristics.
AB  - Hydroxy terminated polybutadiene (HTPB)-chitin based polyurethanes (PUs) with
      controlled hydrophobicity were synthesized using HTPB and toluene diisocyanate
      (TDI). The prepolymer was extended with different mass ratios of chitin and 1,4
      butane diol (BDO). The effect of chitin contents in chain extender (CE)
      proportions on surface properties was studied and investigated. Incorporation of
      chitin contents into the final PU showed decrease in contact angle value of water
      drop, water absorption (%) and swelling behavior. The antibacterial activity of
      the prepared samples was affected by varying the chitin contents in the chemical
      composition of the final PU. The results demonstrated that the use of prepared
      material can be suggested as non-absorbable suture. 

PMID- 24120964
TI  - Effect of different drying methods on chemical composition and bioactivity of tea
      polysaccharides.
AB  - Four polysaccharides (TPS-F, TPS-V, TPS-S and TPS-M) were obtained from tea
      (Camellia sinensis) leaves by freeze-drying, vacuum-drying, spray-drying and
      microwave-vacuum drying, respectively. Their chemical composition and biological
      properties were comparatively studied. The results showed these TPS were similar
      in IR, UV absorption and distribution of molecular weight. However, they showed
      significant differences (P<0.05) in yields of crude polysaccharides and contents
      of protein and total polyphenols. Furthermore, morphological analysis showed
      their surface differed from each other in size and shape when viewed by SEM, from
      which surface of TPS-F was rough and porous, surface of TPS-S was evenly
      particles, and surfaces of the other two were similar to anomalistic bricks. In
      addition, the bioactivity of them was also evaluated. It was found TPS-F
      exhibited relatively better ability on metal chelating and superoxide radicals
      scavenging assays than others, and TPS-V exhibited higher ability on alpha
      glycosidase and alpha-amylase inhibition assays than others with inhibitory
      percentages of 82.75% and 92.8%. 

PMID- 24120965
TI  - Enzymatic properties of stingray Dasyatis pastinaca group V, IIA and IB
      phospholipases A(2): a comparative study.
AB  - In the present study, we have purified the group V phospholipase from the heart
      of cartilaginous fish stingray Dasyatis pastinaca and compared its biochemical
      properties with group IIA (sPLA2-IIA) and IB (sPLA2-IB) phospholipases previously
      purified from pancreas and intestine, respectively. Group V phospholipase (sPLA2
      V) was purified to homogeneity by heat treatment, ammonium sulphate precipitation
      and RP-HPLC. The N-terminal sequence of the purified sPLA2-V exhibits a high
      degree of homology with those of mammal. The enzyme was found to be monomeric
      with a molecular mass estimation of 14 kDa. The specific activity of the purified
      enzyme, measured at pH 8 and 37  degrees C was 52 U/mg. Like sPLA2-IB and sPLA2
      IIA, the sPLA2-V is found to be stable between pH 3 and 11 after 30 min of
      incubation. The purified sPLA2-V retained 65% of its activity after 10 min of
      incubation at 70  degrees C and it absolutely requires Ca(2+) for enzymatic
      activity. In addition it displayed high tolerance to organic solvents. Kinetic
      parameters Kmapp, kcat and the deduced catalytic efficiency (kcat/Kmapp) of the
      purified group-V, -IB and -IIA PLA2s were determined using
      phosphatidylethanolamine (PE), phosphatidylcholine (PC) or phosphatidylserine
      (PS) as substrate. The three enzymes hydrolyze the zwiterionic PE and PC
      substrates more efficiently than anionic PS substrate.

PMID- 24120966
TI  - Effects of benznidazole:cyclodextrin complexes on the drug bioavailability upon
      oral administration to rats.
AB  - Benznidazole (BZL) is the drug of choice for the treatment of Chagas' disease, a
      neglected parasitic infection. It is poorly soluble in water, which may have a
      direct impact into its bioavailability. Thus, the aim of this study was to
      evaluate the impact of stoichiometric and non-stoichiometric BZL-cyclodextrins
      (CDs) complexes on the bioavailability of BZL. The interaction of BZL with the
      CDs was investigated using differential scanning calorimetry (DSC), scanning
      electron microscopy (SEM), X-ray diffractometry (XRD), phase solubility and
      dissolution studies. The oral bioavailability of BZL from these complexes was
      examined in rats. Both BZL solubility and dissolution increased by CD
      complexation. The inclusion complexes were found to improve the dissolution rate
      of BZL by 4.3-fold in comparison with BZL alone. Complexation of BZL with CDs
      derivatives increased its plasma concentrations when fed to rats, with AUC0-5
      values increasing up to 3.7-fold and Cmax increasing 2.5-fold in comparison with
      BZL alone. It should be note that a remarkable increase in these parameters was
      observed in the case of the non-stoichiometric complexes. Thus, these CDs
      complexes could be used to efficiently deliver BZL in patients suffering from
      Chagas' disease. 

PMID- 24120967
TI  - Anti-cancer activity of compounds from Bauhinia strychnifolia stem.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem and root of Bauhinia strychnifolia Craib
      (Fabaceae family) have been traditionally used in Thailand to treat fever,
      alcoholic toxication, allergy and cancer. An EtOH extract of Bauhinia
      strychnifolia showed good inhibitory activity against several cancer cell lines
      including HT-29, HeLa, MCF-7 and KB. As there has been no previous reports on
      chemical constituents of Bauhinia strychnifolia, this study is aimed to isolate
      the pure compounds with anti-cancer activity. MATERIALS AND METHODS: Five pure
      compounds were isolated from EtOH extract of Bauhinia strychnifolia stem using
      silica gel, dianion HP-20 and sephadex LH-20 column chromatography and were
      tested for their cytotoxic effects against HT-29, HeLa, MCF-7 and KB cell lines
      using the Sulforhodamine B (SRB) assay. RESULTS: Among five compounds,
      3,5,7,3',5'-pentahydroxyflavanonol-3-O-alpha-l-rhamnopyranoside (2) possessed
      very potent activity against KB (IC50=0.00054MUg/mL), HT-29 (IC50=0.00217
      MUg/mL), MCF-7 (IC50=0.0585 MUg/mL) and HeLa cells (IC50=0.0692 MUg/mL). 3,5,7
      Trihydroxychromone-3-O-alpha-l-rhamnopyranoside (3) also showed good activity
      against HT-29 (IC50=0.02366 MUg/mL), KB (IC50=0.0412 MUg/mL) and MCF-7
      (IC50=0.297 MUg/mL), respectively. The activity of 2 (IC50=0.00054 MUg/mL)
      against KB cell was ten times higher than that of the positive control,
      Camptothecin (anti-cancer drug, IC50=0.0057 MUg/mL). All compounds did not show
      any cytotoxicity with normal cells at the concentration of 1 MUg/mL. CONCLUSION:
      This is the first report of compounds 2 and 3 on anti-cancer activity and based
      on the anti-cancer activity of extracts and pure compounds isolated from Bauhinia
      strychnifolia stem, it might be suggested that this plant could be useful for
      treatment of cancer.

PMID- 24120968
TI  - Infusion-line pressure as a real-time monitor of convection-enhanced delivery in
      pre-clinical models.
AB  - BACKGROUND: Acute convection-enhanced delivery (CED) is a neurosurgical delivery
      technique that allows for precise and uniform distribution of an infusate to a
      brain structure. It remains experimental due to difficulties in ensuring
      successful delivery. Real-time monitoring is able to provide immediate feedback
      on cannula placement, infusate distribution, and if the infusion is proceeding as
      planned or is failing due to reflux or catheter obstruction. NEW METHOD: Pressure
      gradient is the driving force behind CED, with the infusion pressure being
      directly proportional to the flow-rate. The aim of this study was to assess the
      feasibility of using infusion-line pressure profiling to distinguish in real-time
      between succeeding and failing CED infusions. To do so we delivered cresyl violet
      dye at 0.5, 1.0 and 2.0 MUl/min via CED in vitro using 0.6% agarose gel and in
      vivo to the rat striatum. RESULTS: Infusions that failed in agarose gel models
      could only be differentiated late during the procedures. In the rat in vivo
      model, the infusion-line profiles of obstructed infusions were not distinctive
      from those of successful infusions. COMPARISON WITH EXISTING METHOD:
      Intraoperative magnetic resonance imaging (MRI) is used for real-time
      visualisation of cannula placement and infusate distribution. Particularly for
      animal pre-clinical work, it would be advantageous to supplement MRI with a
      cheap, accessible technique to monitor infusions and provide a real-time measure
      of infusion success or failure. CONCLUSIONS: Infusion-line pressure monitoring
      was of limited value in identifying successful CED with small volume infusions,
      whilst its utility for large volume infusion remains unknown.

PMID- 24120969
TI  - Comparative reactivity of the myeloperoxidase-derived oxidants hypochlorous acid
      and hypothiocyanous acid with human coronary artery endothelial cells.
AB  - In the immune response, hypohalous acids are generated by activated leukocytes
      via the release of myeloperoxidase and the formation of H2O2. Although these
      oxidants have important bactericidal properties, they have also been implicated
      in causing tissue damage in inflammatory diseases, including atherosclerosis.
      Hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) are the major oxidants
      formed by myeloperoxidase under physiological conditions, with the ratio of these
      oxidants dependent on diet and smoking status. HOCl is highly reactive and causes
      marked cellular damage, but few data are available on the effects of HOSCN on
      mammalian cells. In this study, we have compared the actions of HOCl and HOSCN on
      human coronary artery endothelial cells (HCAEC). HOCl reacts rapidly with the
      cells, resulting in extensive cell death by both apoptosis and necrosis, with
      necrosis dominating at higher oxidant doses. In contrast, HOSCN is consumed more
      slowly, with cell death occurring only by apoptosis. Exposure of HCAEC to HOCl
      and HOSCN induces changes in mitochondrial membrane permeability, which, in the
      case of HOSCN, is associated with mitochondrial release of proapoptotic factors,
      including cytochrome c, apoptosis-inducing factor, and endonuclease G. With each
      oxidant, apoptosis appears to be caspase-independent, with the inactivation of
      caspases 3/7 observed, and pretreatment of the cells with the caspase inhibitor Z
      VAD-fmk having no effect on the extent of cell death. Loss of cellular thiols,
      depletion of glutathione, and the inactivation of thiol-dependent enzymes,
      including glyceraldehyde-3-phosphate dehydrogenase, were seen with both oxidants,
      though to a much greater extent with HOCl. The ability of myeloperoxidase-derived
      oxidants to induce endothelial cell apoptosis may contribute to the formation of
      unstable lesions in atherosclerosis. The results with HOSCN may be particularly
      significant for smokers, who have elevated plasma levels of SCN(-), the precursor
      of this oxidant. 

PMID- 24120970
TI  - Independent roles of methionine sulfoxide reductase A in mitochondrial ATP
      synthesis and as antioxidant in retinal pigment epithelial cells.
AB  - The antioxidant enzyme methionine sulfoxide reductase A (MsrA) is highly
      expressed in the retinal pigment epithelium (RPE), a support tissue for
      neighboring photoreceptors. MsrA protein levels correlate with sensitivity of RPE
      in culture to experimental oxidative stress. To investigate whether and how MsrA
      affects RPE functionality regardless of oxidative stress, we tested the effects
      of acute silencing or overexpression of MsrA on the phagocytosis of photoreceptor
      outer segment fragments (POS), a demanding, daily function of the RPE that is
      essential for vision. Endogenous MsrA localized to mitochondria and cytosol of
      rat RPE in culture. RPE cells manipulated to express higher or lower levels of
      MsrA than control cells showed no signs of cell death but increased or decreased,
      respectively, POS binding as well as engulfment. These effects of altered MsrA
      protein concentration on phagocytosis were independent of the levels of oxidative
      stress. However, altering MsrA expression had no effect on phagocytosis when
      mitochondrial respiration was inhibited. Furthermore, ATP content directly
      correlated with MsrA protein levels in RPE cells that used mitochondrial
      oxidative phosphorylation for ATP synthesis but not in RPE cells that relied on
      glycolysis alone. Overexpressing MsrA was sufficient to increase specifically the
      activity of complex IV of the respiratory chain, whereas activity of complex II
      and mitochondrial content were unaffected. Thus, MsrA probably enhances ATP
      synthesis by increasing complex IV activity. Such contribution of MsrA to energy
      metabolism is independent of its function in protection from elevated oxidative
      stress but contributes to routine but vital photoreceptor support by RPE cells. 

PMID- 24120971
TI  - Protein tyrosine phosphatase 1B inhibition ameliorates palmitate-induced
      mitochondrial dysfunction and apoptosis in skeletal muscle cells.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin
      signaling pathway and is considered a promising therapeutic target in the
      treatment of diabetes. However, the role of PTP1B in palmitate-induced
      mitochondrial dysfunction and apoptosis in skeletal muscle cells has not been
      studied. Here we investigate the effects of PTP1B modulation on mitochondrial
      function and apoptosis and elucidate the underlying mechanisms in skeletal muscle
      cells. PTP1B inhibition significantly reduced palmitate-induced mitochondrial
      dysfunction and apoptosis in C2C12 cells, as these cells had increased expression
      levels of PGC-1alpha, Tfam, and NRF-1; enhanced ATP level and cellular viability;
      decreased TUNEL-positive cells; and decreased caspase-3 and -9 activity.
      Alternatively, overexpression of PTP1B resulted in mitochondrial dysfunction and
      apoptosis in these cells. PTP1B silencing improved mitochondrial dysfunction by
      an increase in the expression of SIRT1 and a reduction in the phosphorylation of
      p65 NF-kappaB. The protection from palmitate-induced apoptosis by PTP1B
      inhibition was also accompanied by a decrease in protein level of serine
      palmitoyl transferase, thus resulting in lower ceramide content in muscle cells.
      Exogenous addition of C2-ceramide to PTP1B-knockdown cells led to a reduced
      generation of reactive oxygen species (ROS), whereas PTP1B overexpression
      demonstrated an elevated ROS production in myotubes. In addition, PTP1B
      inhibition was accompanied by decreased JNK phosphorylation and increased insulin
      stimulated Akt (Ser473) phosphorylation, whereas overexpression of PTP1B had the
      opposite effect. The overexpression of PTP1B also induced the nuclear
      localization of FOXO-1, but in contrast, suppression of PTP1B reduced palmitate
      induced nuclear localization of FOXO-1. In summary, our results indicate that
      PTP1B modulation results in (1) alterations in mitochondrial function by changes
      in the activity of SIRT1/NF-kappaB/PGC-1alpha pathways and (2) changes in
      apoptosis that result from either a direct effect of PTP1B on the insulin
      signaling pathway or an indirect influence on ceramide content, ROS generation,
      JNK activation, and FOXO-1 nuclear translocation. 

PMID- 24120972
TI  - Regional long-term model of radioactivity dispersion and fate in the Northwestern
      Pacific and adjacent seas: application to the Fukushima Dai-ichi accident.
AB  - The compartment model POSEIDON-R was modified and applied to the Northwestern
      Pacific and adjacent seas to simulate the transport and fate of radioactivity in
      the period 1945-2010, and to perform a radiological assessment on the releases of
      radioactivity due to the Fukushima Dai-ichi accident for the period 2011-2040.
      The model predicts the dispersion of radioactivity in the water column and in
      sediments, the transfer of radionuclides throughout the marine food web, and
      subsequent doses to humans due to the consumption of marine products. A generic
      predictive dynamic food-chain model is used instead of the biological
      concentration factor (BCF) approach. The radionuclide uptake model for fish has
      as a central feature the accumulation of radionuclides in the target tissue. The
      three layer structure of the water column makes it possible to describe the
      vertical structure of radioactivity in deep waters. In total 175 compartments
      cover the Northwestern Pacific, the East China and Yellow Seas and the East/Japan
      Sea. The model was validated from (137)Cs data for the period 1945-2010.
      Calculated concentrations of (137)Cs in water, bottom sediments and marine
      organisms in the coastal compartment, before and after the accident, are in close
      agreement with measurements from the Japanese agencies. The agreement for water
      is achieved when an additional continuous flux of 3.6 TBq y(-1) is used for
      underground leakage of contaminated water from the Fukushima Dai-ichi NPP, during
      the three years following the accident. The dynamic food web model predicts that
      due to the delay of the transfer throughout the food web, the concentration of
      (137)Cs for piscivorous fishes returns to background level only in 2016. For the
      year 2011, the calculated individual dose rate for Fukushima Prefecture due to
      consumption of fishery products is 3.6 MUSv y(-1). Following the Fukushima Dai
      ichi accident the collective dose due to ingestion of marine products for Japan
      increased in 2011 by a factor of 6 in comparison with 2010. 

PMID- 24120973
TI  - Clinical care for opioid-using pregnant and postpartum women: the role of
      obstetric providers.
AB  - We review clinical care issues that are related to illicit and therapeutic opioid
      use among pregnant women and women in the postpartum period and outline the major
      responsibilities of obstetrics providers who care for these patients during the
      antepartum, intrapartum, and postpartum periods. Selected patient treatment
      issues are highlighted, and case examples are provided. Securing a strong rapport
      and trust with these patients is crucial for success in delivering high-quality
      obstetric care and in coordinating services with other specialists as needed.
      Obstetrics providers have an ethical obligation to screen, assess, and provide
      brief interventions and referral to specialized treatment for patients with drug
      use disorders. Opioid-dependent pregnant women often can be treated effectively
      with methadone or buprenorphine. These medications are classified as pregnancy
      category C medications by the Food and Drug Administration, and their use in the
      treatment of opioid-dependent pregnant patients should not be considered "off
      label." Except in rare special circumstances, medication-assisted withdrawal
      during pregnancy should be discouraged because of a high relapse rate. Acute pain
      management in this population deserves special consideration because patients who
      use opioids can be hypersensitive to pain and because the use of mixed opioid
      agonist/antagonists can precipitate opioid withdrawal. In the absence of other
      indications, pregnant women who use opioids do not require more intense medical
      care than other pregnant patients to ensure adequate treatment and the best
      possible outcomes. Together with specialists in pain and addiction medicine,
      obstetricians can coordinate comprehensive care for pregnant women who use
      opioids and women who use opioids in the postpartum period. 

PMID- 24120974
TI  - Characterization of grass carp (Ctenopharyngodon idella) IL-17D: molecular
      cloning, functional implication and signal transduction.
AB  - Although the roles of IL-17 family members during inflammation have been
      extensively studied in mammals, their knowledge in lower vertebrates is limited.
      In particular, the biological activities of fish IL-17 and their functional roles
      are largely unknown. In this study, we cloned grass carp IL-17D (gcIL-17D) and
      found that its putative protein possessed the conserved features of IL-17 family
      members. Tissue distribution analysis showed that gcIL-17D was preferentially
      expressed in the mucosal tissues, including skin, gill and intestine.
      Subsequently, the involvement of gcIL-17D in inflammatory response was
      demonstrated by examining the expression profiles of gcIL-17D in head kidney and
      head kidney leukocytes following in vivo bacterial infection and in vitro LPS
      treatment, respectively. Furthermore, recombinant gcIL-17D (rgcIL-17D) was
      prepared in grass carp kidney cells and was able to promote the gene expression
      of some pro-inflammatory cytokines (IL-1beta, TNF-alpha and CXCL-8) in grass carp
      primary head kidney cells, revealing gcIL-17D can function as a pro-inflammatory
      cytokine. Moreover, rgcIL-17D appeared to activate NF-kappaB signaling by
      modulating the phosphorylation of IkappaBalpha and up-regulated CXCL-8 mRNA
      expression possibly through NF-kappaB pathway. Our data shed new light on the
      functional role of teleost IL-17D in inflammatory response.

PMID- 24120975
TI  - Molecular signatures at imminent death: hemocyte gene expression profiling of
      shrimp succumbing to viral and fungal infections.
AB  - Infectious diseases represent the most serious threat to shrimp farming
      worldwide. Understanding the molecular mechanisms driving shrimp-pathogen
      interactions is necessary for developing strategies to control disease outbreaks
      in shrimp production systems. In the current study, we experimentally reproduced
      mortality events using standardized infections to characterize the hemocyte
      transcriptome response of the shrimp Litopenaeus vannamei succumbing to
      infectious diseases. By using a high-throughput microfluidic RT-qPCR approach, we
      identified molecular signatures in shrimp during lethal infections caused by the
      White Spot Syndrome Virus (WSSV) or the filamentous fungus Fusarium solani. We
      successfully identified gene expression signatures shared by both infections but
      also pathogen-specific gene responses. Interestingly, whereas lethal WSSV
      infection induced the expression of antiviral-related genes, the transcript
      abundance of many antimicrobial effectors was reduced by lethal F. solani
      infection. To our knowledge, this is the first report of the immune-gene
      repertoire of infected shrimp at the brink of death. 

PMID- 24120976
TI  - Percutaneous left cardiac sympathetic denervation in a patient with long-QT
      syndrome.

PMID- 24120977
TI  - New regurgitation after aortic valve replacement with a stented bovine
      pericardial prosthesis: is the leak paravalvular or non-paravalvular?

PMID- 24120978
TI  - Discovery of novel anxiolytic agents--the trials and tribulations of pre-clinical
      models of anxiety.
AB  - Anxiety disorders are the most common class of mental disorders present in the
      general population with an estimated lifetime prevalence of any anxiety disorder
      being approximately 15%, while the 12-month prevalence is more than 10%. They are
      classified into simple phobias, social phobias, obsessive-compulsive disorder
      (OCD) and panic attacks. Anxiety disorders are more prevalent in females than
      males and respond to pharmacological and non-pharmacological (behavioral)
      treatments. Anxiety disorders are complex with genetic and environmental factors
      interacting to produce the final psychopathology. There are many tests used to
      detect behaviors that indicate heightened anxiety in rodents however there are
      few pathological models of anxiety in rodents. Most compound testing is performed
      on naive, non-pathologically anxious, male animals which is a potential
      limitation to current strategies since these animals do not reflect the anxious
      patient. This article briefly describes some of the most common anxiety tests
      used in rodent research and concludes with a short perspective on areas the field
      could concentrate on to improve the understanding and successful translation of
      novel targets into new therapies in the clinic. 

PMID- 24120979
TI  - Direct analysis of human breath ammonia using corona discharge ion mobility
      spectrometry.
AB  - In this study, ammonia in human breath was directly determined using corona
      discharge ionization ion mobility spectrometry (CD-IMS) technique with several
      important advantages including high sensitivity, low cost, high speed, and ease
      of maintenance. The temperature effect on the ammonia signal was evaluated too.
      The results indicated that the best temperature for the investigation of breath
      ammonia was 150 degrees C. The analytical results showed that the linear dynamic
      range was between 12 and 810ppb and the detection limit was 6.6ppb. The relative
      standard deviation (RSD) was obtained to be 5, 3, and 3 for 290, 348, and 522ppb,
      respectively. The amounts of ammonia in breath of eight healthy volunteers were
      measured. The values were between 236 and 1218ppb. Also, the inequality in breath
      ammonia levels was scrutinized over a 6h working day for three healthy
      volunteers. The results showed a drop in breath ammonia from the morning amount
      to the mid-day measurement and then, a progressive increase while the day
      continued. In addition, the amounts of ammonia were determined to be 1494-1553ppb
      in exhaled breath of two renal failure patients. The results obtained in this
      work revealed that the method was conveniently established without any
      considerable sample pretreatment for direct analysis of ammonia in human breath. 

PMID- 24120980
TI  - Pharmacokinetics study of hemin in rats by applying (58)Fe-extrinsically labeling
      techniques in combination with ICP-MS method.
AB  - Iron is a challenging element due to its high background in various matrixes
      including blood, tissues even in the air and it is urgent to develop a method for
      the accurate determination of iron in bio-samples. After optimization of mass
      spectrometric conditions using collision cell technology and compensating for
      interference using a mathematical correction equation, an inductively coupled
      plasma mass spectrometry (ICP-MS) method for the quantitative determination of
      (58)Fe originating from hemin extrinsically labeled avoiding endogenous
      interference was developed. After a single step of dilution, analysis of each
      sample was completed within 1.5min. The assay was linear in the concentration
      range from 0.005 to 1.0MUg/ml. The precisions and accuracies determined within
      three consecutive days were in acceptable limits and there was no significant
      matrix effect. The optimized method was successfully applied to a pharmacokinetic
      study of (58)Fe originating from hemin extrinsically labeled and iron absorption
      measured in rats was 1.07%. Those indicated that extrinsically label techniques
      in combination with ICP-MS will become a new tool for the analysis of iron
      preparations and other endogenous substances. 

PMID- 24120981
TI  - Algorithm for weight loss after gastric bypass surgery considering body mass
      index, gender, and age from the Bariatric Outcome Longitudinal Database (BOLD).
AB  - BACKGROUND: Insight into the effects of gender and age on bariatric weight loss
      can be disturbed by the well-known influence of initial body mass index (BMI) on
      excess weight loss (%EWL). Alternative metrics can be found that eliminate this
      influence. Their formulas can be used to construct an algorithm in which mean
      weight loss becomes a constant value, describing the effectiveness of the
      operation independent of the initial BMI. The objective of this study was to
      create an algorithm describing weight loss after LRYGB in search for a better
      outcome metric to demonstrate unequivocally the influence of patient
      characteristics on bariatric results. METHODS: Nadir weight loss results of BOLD
      patients, grouped by gender and age (<40 yr and >=40 yr), with >=2 years follow
      up after LRYGB and initial BMI >=30 and<80 kg/m(2), are expressed in 26 different
      metrics with formula: 100%*(initial BMI - nadir BMI)/(initial BMI - a) with
      "reference BMI" a = 0-25 kg/m(2). For each subgroup, the "optimal reference BMI"
      (a) generating the smallest deviation and without significant difference in
      outcome between lighter and heavier patients is used to construct an algorithm
      (Mann-Whitney U test; P<.0002). Mean nadir relative weight loss results (b) are
      compared. RESULTS: A total of 8945 patients met inclusion criteria (mean initial
      BMI, 47.7 kg/m(2); median age, 48 yr; 20.0% male). Both female subgroups had
      optimal reference BMI: a = 10 kg/m(2); both male subgroups: a = 17 kg/m(2). LRYGB
      effectiveness (b) was significantly higher for younger patients and for female
      patients. The %EWL metric rendered different significances. CONCLUSIONS: Both
      genders have age-independent metrics for which nadir relative weight loss after
      LRYGB is not influenced by initial BMI. The resulting algorithm nadir BMI = a +
      (100%-b) * (initial BMI-a) consists of an inert part (a = 10-17 kg/m(2)) on which
      the bariatric effectiveness (b) does not act and an alterable part (initial BMI
      a) on which it does. The proposed metric percentage alterable weight loss (%AWL)
      reduces results to constant values for bariatric effectiveness (b), facilitating
      research on the precise effect of patient characteristics and surgical variables
      on postoperative weight loss better than %EWL, a metric able to produce false
      conclusions. Women and younger patients had significantly more weight loss;
      initial BMI had no effect.

PMID- 24120982
TI  - Low levels of C-peptide may not be a sign of pancreatic beta-cell death or
      apoptosis: new insight into pancreatic endocrine function and indications for
      metabolic surgery.

PMID- 24120984
TI  - Variations on bowel obstruction after gastric bypass and management of the
      twisted Roux limb.

PMID- 24120983
TI  - Laparoscopic reversal of Roux-en-Y gastric bypass: technique and utility for
      treatment of endocrine complications.
AB  - BACKGROUND: The anatomic and physiologic changes with Roux-en-Y gastric bypass
      (RYGB) may lead to uncommon but occasionally difficult to treat complications
      such as hyperinsulinemic hypoglycemia with neuroglycopenia and recalcitrant
      hypocalcemia associated to hypoparathyroidism. Medical management of these
      complications is challenging. Laparoscopic reversal of RYGB anatomy with
      restoration of pyloric function and duodenal continuity is a potential treatment.
      The objective of this study was to present the indications, surgical technique,
      and clinical outcomes of laparoscopic reversal of RYGB. METHODS: Prospective
      study of consecutive patients offered laparoscopic reversal of RYGB. RESULTS:
      Five patients with remote laparoscopic RYGB underwent laparoscopic reversal of
      RYGB to normal anatomy (n = 2) or modified sleeve gastrectomy (n = 3).
      Indications were medically refractory hyperinsulinemic hypoglycemia with
      neuroglycopenia (n = 3), recalcitrant hypocalcemia with hypoparathyroidism (n =
      1), and both conditions simultaneously (n = 1). Before reversal, all patients had
      a gastrostomy tube placed in the excluded stomach to document improvement of
      symptoms. Laparoscopic reversal was accomplished successfully in all patients.
      Three postoperative complications occurred: bleeding that required transfusion,
      gallstone pancreatitis, and a superficial trocar site infection. Average length
      of stay was 3 days. At a mean follow-up of 12 months (range 3 to 22), no
      additional episodes of neuroglycopenia occurred, average number of hypoglycemic
      episodes per week decreased from 18.5 +/- 12.4 to 1.5 +/- 1.9 (P = .05), and
      hypocalcemia became responsive to oral replacement therapy in both patients.
      CONCLUSIONS: Laparoscopic reversal of RYGB to normal anatomy or modified sleeve
      gastrectomy is feasible and may be a therapeutic option for selected patients
      with medically refractory hyperinsulinemic hypoglycemia and/or recalcitrant
      hypocalcemia associated with hypoparathyroidism.

PMID- 24120986
TI  - Physical activity and the brain: a review of this dynamic, bi-directional
      relationship.
AB  - The brain plays a major role in regulating physical activity behavior and
      exercise performance. Regular physical activity may also play a key role in the
      prevention and treatment of various neurological conditions, such as Parkinson's
      disease, Alzheimer's disease, depression, and cognitive function. This implies
      that not only does the brain (or the nervous system) regulate aspects of physical
      activity, but also that physical activity may potentially influence brain-related
      function and outcomes. This review details this bi-directional relationship and
      addresses its implications for improving physical activity, exercise performance,
      and brain-related function and outcomes. 

PMID- 24120985
TI  - Sexual functioning and sex hormones in persons with extreme obesity and seeking
      surgical and nonsurgical weight loss.
AB  - BACKGROUND: Many individuals with obesity are motivated to lose weight to improve
      weight-related co-morbidities or psychosocial functioning, including sexual
      functioning. Few studies have documented rates of sexual dysfunction in persons
      with obesity. This study investigated sexual functioning, sex hormones, and
      relevant psychosocial constructs in individuals with obesity who sought surgical
      and nonsurgical weight loss. METHODS: One hundred forty-one bariatric surgery
      patients (median BMI [25th percentile, 75th percentile] 44.6 [41.4, 50.1]) and
      109 individuals (BMI = 40.0 [38.0, 44.0]) who sought nonsurgical weight loss
      participated. Sexual functioning was assessed by the Female Sexual Function Index
      (FSFI) and the International Index of Erectile Function (IIEF). Hormones were
      assessed by blood assay. Quality of life, body image, depressive symptoms, and
      marital adjustment were assessed by validated questionnaires. RESULTS: Fifty-one
      percent of women presenting for bariatric surgery reported a sexual dysfunction;
      36% of men presenting for bariatric surgery reported erectile dysfunction (ED).
      This is in contrast to 41% of women who sought nonsurgical weight loss and
      reported a sexual dysfunction and 20% of men who sought nonsurgical weight loss
      and reported ED. These differences were not statistically significant. Sexual
      dysfunction was strongly associated with psychosocial distress in women; these
      relationships were less strong and less consistent among men. Sexual dysfunction
      was unrelated to sex hormones, except for sex hormone binding globulin (SHGB) in
      women. CONCLUSION: Women and men who present for bariatric surgery, compared with
      individuals who sought nonsurgical weight loss, were not significantly more
      likely to experience a sexual dysfunction. There were few differences in
      reproductive hormones and psychosocial constructs between candidates for
      bariatric surgery and individuals interested in nonsurgical weight loss.

PMID- 24120987
TI  - Protective effects of lycopene against methylmercury-induced neurotoxicity in
      cultured rat cerebellar granule neurons.
AB  - Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the
      central nervous system. Oxidative stress and mitochondrial dysfunction are widely
      accepted as central pathogenic mechanisms of MeHg-mediated neurotoxicity.
      Lycopene, a carotenoid compound, is a potent antioxidant with demonstrated
      neuroprotective properties in several experimental models of oxidative damage.
      The present study was designed to investigate whether lycopene could provide
      protective effects against MeHg-induced neurotoxicity in cultured rat cerebellar
      granule neurons (CGNs). The cultured CGNs were pretreated with different dose of
      lycopene for 2h, followed by the challenge with 500nM MeHg for 12h. It was found
      that MeHg exposure caused the loss of cell viability and the LDH release.
      Furthermore, we demonstrated that MeHg exposure significantly elevated
      intracellular reactive oxygen species generation and mitochondria-derived
      superoxide production, caused disruption of mitochondrial membrane potential and
      opening of mPTP, inhibited mitochondrial complex enzyme activities (complex III
      and complex IV), reduced ATP generation and decreased mtDNA copy numbers and
      mtDNA transcript levels. However, each of these oxidative damages was efficiently
      attenuated by lycopene pretreatment. Collectively, these results suggest that
      lycopene affords protection against MeHg-induced neurotoxicity in CGNs, and these
      beneficial effects of lycopene may be attributable to its roles in preventing
      mitochondrial dysfunction. 

PMID- 24120988
TI  - Anti-inflammatory substances can influence some glial cell types but not others.
AB  - In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied
      cytokine release after exposure with 1 ng/ml LPS for 0.5-24 h. Dexamethasone and
      corticosterone exposure served as controls. We focused on whether naloxone,
      ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on
      astrocytes, could affect the release of TNF-alpha and IL-1beta in microglia. Our
      results show that neither ultralow (10(-12) M) nor high (10(-6) M) concentrations
      of these agents had demonstrable effects on cytokine release in microglia. The
      results indicate that anti-inflammatory substances exert specific influences on
      different glial cell types. Astrocytes seem to be functional targets for anti
      inflammatory substances while microglia respond directly to inflammatory stimuli
      and are thus more sensitive to anti-inflammatory substances like corticoids. The
      physiological relevance might be that astrocyte dysfunction influences neuronal
      signalling both due to direct disturbance of astrocyte functions and in the
      communication within the astrocyte networks. When the signalling between
      astrocytes is working, then microglia produce less pro-inflammatory cytokines.

PMID- 24120989
TI  - Effect of atrial natriuretic peptide on reactive oxygen species-induced by
      hydrogen peroxide in THP-1 monocytes: role in cell growth, migration and cytokine
      release.
AB  - Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different
      biological actions in the immune system. The aim of the present study was to
      investigate in THP-1 monocytes the ANP effect on hydrogen peroxide (H2O2)-induced
      Reactive Oxygen Species (ROS), cell proliferation and migration. A significant
      increase of H2O2-dependent ROS production was induced by physiological
      concentration of ANP (10(-10)M). The ANP action was partially affected by cell
      pretreatment with PD98059, an inhibitor of mitogen activated-protein kinases
      (MAPK) as well as by wortmannin, an inhibitor of phosphatidylinositol 3-kinase
      (PI3K) and totally suppressed by diphenylene iodonium (DPI), an inhibitor of the
      enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The hormone
      effect was mimicked by cANF and an ANP/NPR-C signaling pathway was studied using
      pertussis toxin (PTX). A significant increase of H2O2-induced cell migration was
      observed after ANP (10(-10)M) treatment, conversely a decrease of THP-1
      proliferation, due to cell death, was found. Both ANP actions were partially
      prevented by DPI. Moreover, H2O2-induced release of IL-9, TNF-alpha, MIP-1alpha
      and MIP-1beta was not counteracted by DPI, whereas no effect was observed in any
      experimental condition for both IL-6 and IL-1beta. Our results support the view
      that ANP can play a key role during the inflammatory process. 

PMID- 24120990
TI  - Converting differential-equation models of biological systems to membrane
      computing.
AB  - This paper presents a method to convert the deterministic, continuous
      representation of a biological system by ordinary differential equations into a
      non-deterministic, discrete membrane computation. The dynamics of the membrane
      computation is governed by rewrite rules operating at certain rates. That has the
      advantage of applying accurately to small systems, and to expressing rates of
      change that are determined locally, by region, but not necessary globally. Such
      spatial information augments the standard differentiable approach to provide a
      more realistic model. A biological case study of the ligand-receptor network of
      protein TGF-beta is used to validate the effectiveness of the conversion method.
      It demonstrates the sense in which the behaviours and properties of the system
      are better preserved in the membrane computing model, suggesting that the
      proposed conversion method may prove useful for biological systems in particular.

PMID- 24120992
TI  - Categorization of two-dimensional and three-dimensional stimuli by 18-month-old
      infants.
AB  - In two experiments, 18-month-old infants' categorization of 3D replicas and 2D
      photographs of the same animals and vehicles were compared to explore infants'
      flexibility in categorization across different object representations. Using a
      sequential touching procedure, infants completed one superordinate and two basic
      level categorization tasks with 3D replicas, 2D cut out photographs, or 2D images
      on photo cubes ("2D cubes"). For superordinate sets, 3D replicas elicited longer
      mean run lengths than 2D cut outs, and 3D replicas elicited equivalent mean run
      lengths as 2D cubes. For basic-level sets, infants categorized high-contrast
      animal sets when presented with 3D replicas, but they failed to categorize any of
      the 2D photograph sets. Categorization processes appear to differ for 3D and 2D
      stimuli, and infants' discovery of object properties over time while manipulating
      objects may facilitate categorization, as least at the superordinate level. These
      findings are discussed in the context of infants' representation abilities and
      the integration of perception and action. 

PMID- 24120991
TI  - The tumor suppressor Chd5 is induced during neuronal differentiation in the
      developing mouse brain.
AB  - Epigenetic regulation of gene expression orchestrates dynamic cellular processes
      that become perturbed in human disease. An understanding of how subversion of
      chromatin-mediated events leads to pathologies such as cancer and
      neurodevelopmental syndromes may offer better treatment options for these
      pathological conditions. Chromodomain Helicase DNA-binding protein 5 (CHD5) is a
      dosage-sensitive tumor suppressor that is inactivated in human cancers, including
      neural-associated malignancies such as neuroblastoma and glioma. Here we report a
      detailed analysis of the temporal and cell type-specific expression pattern of
      Chd5 in the mammalian brain. By analyzing endogenous Chd5 protein expression
      during mouse embryogenesis, in the neonate, and in the adult, we found that Chd5
      is expressed broadly in multiple brain regions, that Chd5 sub-cellular
      localization undergoes a switch from the cytoplasm to the nucleus during mid
      gestation, and that Chd5 expression is retained at high levels in differentiated
      neurons of the adult. These findings may have important implications for defining
      the role of CHD5-mediated chromatin dynamics in the brain and for elucidating how
      perturbation of these epigenetic processes leads to neuronal malignancies,
      neurodegenerative diseases, and neurodevelopmental syndromes. 

PMID- 24120993
TI  - Revisiting the diffusion approximation to estimate evolutionary rates of gene
      family diversification.
AB  - Genetic diversity in multigene families is shaped by multiple processes,
      including gene conversion and point mutation. Because multi-gene families are
      involved in crucial traits of organisms, quantifying the rates of their genetic
      diversification is important. With increasing availability of genomic data, there
      is a growing need for quantitative approaches that integrate the molecular
      evolution of gene families with their higher-scale function. In this study, we
      integrate a stochastic simulation framework with population genetics theory,
      namely the diffusion approximation, to investigate the dynamics of genetic
      diversification in a gene family. Duplicated genes can diverge and encode new
      functions as a result of point mutation, and become more similar through gene
      conversion. To model the evolution of pairwise identity in a multigene family, we
      first consider all conversion and mutation events in a discrete manner, keeping
      track of their details and times of occurrence; second we consider only the
      infinitesimal effect of these processes on pairwise identity accounting for
      random sampling of genes and positions. The purely stochastic approach is closer
      to biological reality and is based on many explicit parameters, such as
      conversion tract length and family size, but is more challenging analytically.
      The population genetics approach is an approximation accounting implicitly for
      point mutation and gene conversion, only in terms of per-site average
      probabilities. Comparison of these two approaches across a range of parameter
      combinations reveals that they are not entirely equivalent, but that for certain
      relevant regimes they do match. As an application of this modelling framework, we
      consider the distribution of nucleotide identity among VSG genes of African
      trypanosomes, representing the most prominent example of a multi-gene family
      mediating parasite antigenic variation and within-host immune evasion. 

PMID- 24120994
TI  - Minimum dynamic core in consciousness.

PMID- 24120995
TI  - Response to Susilo and Duchaine: beyond neuropsychological dissociations in
      understanding face and word representations.

PMID- 24120996
TI  - Clinical strategies to enhance thymic recovery after allogeneic hematopoietic
      stem cell transplantation.
AB  - The thymus is particularly sensitive to injury caused by cytoreductive chemo- or
      radiation therapy, shock, infection and graft versus host disease. Insufficient
      thymic recovery has been directly correlated with increased risk of opportunistic
      infections and poor clinical outcomes in recipients of allogeneic hematopoietic
      stem cell transplantation (allo-HSCT). Prolonged immune deficiency is
      particularly pronounced in older patients whose thymi are already significantly
      impaired due to age-related thymic involution. Preclinical and clinical studies
      have revealed several strategies that can enhance thymic function and immune
      reconstitution after transplant, including sex steroid ablation, growth factors
      (growth hormone, keratinocyte growth factor, insulin-like growth factor 1,
      interleukin-7) and ex vivo generated precursor T cells. In addition, recent
      studies have shown that other approaches, such as interleukein-22 and nutritional
      changes, may represent additional candidates to enhance thymic regeneration. In
      this review we provide updates on these strategies and comment on their potential
      to be translated into clinical therapies. 

PMID- 24120997
TI  - The rescue of microtubule-dependent traffic recovers mitochondrial function in
      Parkinson's disease.
AB  - In Parkinson's disease mitochondrial dysfunction can lead to a deficient ATP
      supply to microtubule protein motors leading to mitochondrial axonal transport
      disruption. Compromised axonal transport will then lead to a disorganized
      distribution of mitochondria and other organelles in the cell, as well as, the
      accumulation of aggregated proteins like alpha-synuclein. Moreover, axonal
      transport disruption can trigger synaptic accumulation of autophagosomes packed
      with damaged mitochondria and protein aggregates promoting synaptic failure. We
      previously observed that neuronal-like cells with an inherent mitochondrial
      impairment derived from PD patients contain a disorganized microtubule network,
      as well as, alpha-synuclein oligomer accumulation. In this work we provide new
      evidence that an agent that promotes microtubule network assembly, NAP
      (davunetide), improves microtubule-dependent traffic, restores the autophagic
      flux and potentiates autophagosome-lysosome fusion leading to autophagic vacuole
      clearance in Parkinson's disease cells. Moreover, NAP is capable of efficiently
      reducing alpha-synuclein oligomer content and its sequestration by the
      mitochondria. Most interestingly, NAP decreases mitochondrial ubiquitination
      levels, as well as, increases mitochondrial membrane potential indicating a
      rescue in mitochondrial function. Overall, we demonstrate that by improving
      microtubule-mediated traffic, we can avoid mitochondrial-induced damage and thus
      recover cell homeostasis. These results prove that NAP may be a promising
      therapeutic lead candidate for neurodegenerative diseases that involve axonal
      transport failure and mitochondrial impairment as hallmarks, like Parkinson's
      disease and related disorders. 

PMID- 24120998
TI  - Candidate gene approach to identifying rare genetic variants associated with lone
      atrial fibrillation.
AB  - BACKGROUND: Rare variants in candidate atrial fibrillation (AF) genes have been
      associated with AF in small kindreds. The extent to which such polymorphisms
      contribute to AF is unknown. OBJECTIVE: The purpose of this study was to
      determine the spectrum and prevalence of rare amino acid coding (AAC) variants in
      candidate AF genes in a large cohort of unrelated lone AF probands. METHODS: We
      resequenced 45 candidate genes in 303 European American (EA) lone AF probands
      (186 lone AF probands screened for each gene on average [range 89-303], 63
      screened for all) identified in the Vanderbilt AF Registry (2002-2012). Variants
      detected were screened against 4300 EAs from the Exome Sequencing Project (ESP)
      to identify very rare (minor allele frequency <=0.04%) AAC variants and these
      were tested for AF co-segregation in affected family members where possible.
      RESULTS: Median age at AF onset was 46.0 years [interquartile range 33.0-54.0],
      and 35.6% had a family history of AF. Overall, 63 very rare AAC variants were
      identified in 60 of 303 lone AF probands, and 10 of 19 (52.6%) had evidence of co
      segregation with AF. Among the 63 lone AF probands who had 45 genes screened, the
      very rare variant burden was 22%. Compared with the 4300 EA ESP, the proportion
      of lone AF probands with a very rare AAC variant in CASQ2 and NKX2-5 was
      increased 3-5-fold (P <.05). CONCLUSION: No very rare AAC variants were
      identified in ~80% of lone AF probands. Potential reasons for the lack of very
      rare AAC variants include a complex pattern of inheritance, variants in as yet
      unidentified AF genes or in noncoding regions, and environmental factors.

PMID- 24120999
TI  - Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular
      tachycardia.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an
      inherited arrhythmia syndrome characterized by adrenergically induced ventricular
      arrhythmias in patients with structurally normal hearts. Initiating triggered
      arrhythmias, such as bidirectional ventricular tachycardia, often degenerate into
      reentrant arrhythmias, such as ventricular fibrillation (VF). OBJECTIVE: To
      determine whether the effectiveness of implantable cardioverter-defibrillator
      (ICD) shocks is dependent on rhythm type. METHODS: It is a retrospective study of
      patients with CPVT who had undergone ICD implantation. Thirteen patients received
      ICDs (median age 15 years; range 9-43 years): 7 of 13 (54%) for cardiac arrest
      and 6 of 13 (46%) for syncope despite drug therapy. The median follow-up duration
      was 4.0 years (range 1.7-19.9 years). Nineteen reinterventions occurred,
      excluding generator replacements. Ten patients received 96 shocks (median 4
      shocks; range 1-30 shocks). Eighty-seven shock electrograms were reviewed. Sixty
      three (72%) shocks were appropriate, and 24 (28%) were inappropriate (T-wave
      oversensing 7 [29%], supraventricular arrhythmia 16 [67%], after self-terminating
      VF 1 [4%]). RESULTS: Among appropriate shocks, 20 (32%) were effective in
      terminating sustained arrhythmia and 43 (68%) were ineffective. Shocks delivered
      to triggered arrhythmias nearly always failed (1 of 40 [3%] effective), while
      shocks delivered to VF were usually successful (19 of 23 [83%] effective; P <
      .001). Four patients received 17 appropriate antitachycardia pacing therapies for
      ventricular tachycardia: only 2 (12%) were effective. No patient died.
      CONCLUSIONS: The effectiveness of ICD shock therapy in CPVT depends on the
      mechanism of the rhythm treated. Shocks delivered to initiating triggered
      arrhythmias nearly always fail, whereas those for subsequent VF are usually
      effective. ICD programming in these patients is exceptionally challenging.

PMID- 24121000
TI  - Is long QT syndrome a cardioneurologic or neurocardiologic disorder?

PMID- 24121001
TI  - Implantable cardioverter-defibrillator placement in patients with cardiac
      amyloidosis.

PMID- 24121003
TI  - Gene expression profiling reveals the heterogeneous transcriptional activity of
      Oct3/4 and its possible interaction with Gli2 in mouse embryonic stem cells.
AB  - We examined the transcriptional activity of Oct3/4 (Pou5f1) in mouse embryonic
      stem cells (mESCs) maintained under standard culture conditions to gain a better
      understanding of self-renewal in mESCs. First, we built an expression vector in
      which the Oct3/4 promoter drives the monocistronic transcription of Venus and a
      puromycin-resistant gene via the foot-and-mouth disease virus self-cleaving
      peptide T2A. Then, a genetically-engineered mESC line with the stable integration
      of this vector was isolated and cultured in the presence or absence of puromycin.
      The cultures were subsequently subjected to Illumina expression microarray
      analysis. We identified approximately 4600 probes with statistically significant
      differential expression. The genes involved in nucleic acid synthesis were
      overrepresented in the probe set associated with mESCs maintained in the presence
      of puromycin. In contrast, the genes involved in cell differentiation were
      overrepresented in the probe set associated with mESCs maintained in the absence
      of puromycin. Therefore, it is suggested with these data that the transcriptional
      activity of Oct3/4 fluctuates in mESCs and that Oct3/4 plays an essential role in
      sustaining the basal transcriptional activities required for cell duplication in
      populations with equal differentiation potential. Heterogeneity in the
      transcriptional activity of Oct3/4 was dynamic. Interestingly, we found that
      genes involved in the hedgehog signaling pathway showed unique expression
      profiles in mESCs and validated this observation by RT-PCR analysis. The
      expression of Gli2, Ptch1 and Smo was consistently detected in other types of
      pluripotent stem cells examined in this study. Furthermore, the Gli2 protein was
      heterogeneously detected in mESC nuclei by immunofluorescence microscopy and this
      result correlated with the detection of the Oct3/4 protein. Finally, forced
      activation of Gli2 in mESCs increased their proliferation rate. Collectively, it
      is suggested with these results that Gli2 may play a novel role in the self
      renewal of pluripotent stem cells.

PMID- 24121002
TI  - Transcriptome dynamics during human erythroid differentiation and development.
AB  - To explore the mechanisms controlling erythroid differentiation and development,
      we analyzed the genome-wide transcription dynamics occurring during the
      differentiation of human embryonic stem cells (HESCs) into the erythroid lineage
      and development of embryonic to adult erythropoiesis using high throughput
      sequencing technology. HESCs and erythroid cells at three developmental stages:
      ESER (embryonic), FLER (fetal), and PBER (adult) were analyzed. Our findings
      revealed that the number of expressed genes decreased during differentiation,
      whereas the total expression intensity increased. At each of the three
      transitions (HESCs-ESERs, ESERs-FLERs, and FLERs-PBERs), many differentially
      expressed genes were observed, which were involved in maintaining pluripotency,
      early erythroid specification, rapid cell growth, and cell-cell adhesion and
      interaction. We also discovered dynamic networks and their central nodes in each
      transition. Our study provides a fundamental basis for further investigation of
      erythroid differentiation and development, and has implications in using ESERs
      for transfusion product in clinical settings.

PMID- 24121004
TI  - Interplay between apoptosis and autophagy, a challenging puzzle: new perspectives
      on antitumor chemotherapies.
AB  - Autophagy is a mechanism of protection against various forms of human diseases,
      such as cancer, in which autophagy seems to have an extremely complex role. In
      cancer, there is evidence that autophagy may be oncogenic in some contexts,
      whereas in others it clearly contributes to tumor suppression. In addition,
      studies have demonstrated the existence of a complex relationship between
      autophagy and cell death, determining whether a cell will live or die in response
      to anticancer therapies. Nevertheless, we still need to complete the autophagy
      apoptosis puzzle in the tumor context to better address appropriate chemotherapy
      protocols with autophagy modulators. Generally, tumor cell resistance to
      anticancer induced-apoptosis can be overcome by autophagy inhibition. However,
      when an extensive autophagic stimulus is activated, autophagic cell death is
      observed. In this review, we discuss some details of autophagy and its
      relationship with tumor progression or suppression, as well as role of autophagy
      apoptosis in cancer treatments. 

PMID- 24121006
TI  - Elevated manganese exposure and school-aged children's behavior: a gender
      stratified analysis.
AB  - High levels of waterborne manganese have been associated with problematic
      behavior in school-aged children, however to date this has not been reported for
      children exposed to airborne manganese. The objective of the present study was to
      examine behavioral traits among children with exposure to airborne manganese from
      a ferro-manganese alloy plant, located in the metropolitan region of Salvador,
      Brazil. The study included 34 boys and 36 girls, aged 7-12 years, living in two
      communities within a 3-km radius from the plant. For each child, hair manganese
      levels (MnH) and blood lead (PbB) levels were analyzed by graphite furnace atomic
      absorption spectrometry. The Children's Behavior Check List (CBCL) (Portuguese
      version validated in Brazil) was administered to parents or caregivers, providing
      scale scores of internalizing (withdrawn, somatic complaints, and
      anxious/depressed scales), externalizing (disruptive and aggressive) behaviors
      and a separate scale for attention problems. Median and range for MnH and PbB
      were 11.48 MUg/g (range: 0.52-55.74); 1.1 MUg/dL (range: 0.5-6.1), respectively.
      Spearman correlation analyses showed that several behavioral indices were
      significantly correlated with MnH levels for girls, but not for boys: total
      externalizing behavior (rho=0.484 vs rho=0.041) and attention problem scores
      (rho=0.542 vs rho=0.003) coefficients were significantly at p<0.001 level,
      respectively for girls and boys. No significant correlation was observed with any
      of the internalizing sub-scales. A linear regression model was fitted with the
      total externalizing behavior, inattention and total CBCL scores as dependent
      variables, with log transformed MnH stratified by sex, adjusting for age and
      maternal IQ. Total externalizing behaviors and attention problem scores were
      significantly associated with girls' MnH levels but not with boys'. Adjusting for
      maternal IQ, the beta-coefficients for LogMnH associations with total
      externalizing and attention problems are 8.85 (95%CI 2.44-15.24) and 4.03 (95%CI
      1.50-6.56) for girls. For boys, after adjusting for age, the beta-coefficients
      are 0.08 (95%CI 11.51-11.66) and -0.05 (95%CI 4.34-4.25), respectively. The
      findings of this study suggest a positive association between elevated Mn
      exposure and externalizing behavioral problems and inattention, with girls
      presenting more pronounced effects. Future studies on Mn exposure in children
      should attempt to further elucidate sex and/or gender differences in Mn exposed
      populations.

PMID- 24121005
TI  - Neurodevelopmental effects in children associated with exposure to
      organophosphate pesticides: a systematic review.
AB  - Many studies have investigated the neurodevelopmental effects of prenatal and
      early childhood exposures to organophosphate (OP) pesticides among children, but
      they have not been collectively evaluated. The aim of the present article is to
      synthesize reported evidence over the last decade on OP exposure and
      neurodevelopmental effects in children. The Data Sources were PubMed, Web of
      Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility
      criteria considered were studies assessing exposure to OP pesticides and
      neurodevelopmental effects in children from birth to 18 years of age, published
      between 2002 and 2012 in English or Spanish. Twenty-seven articles met the
      eligibility criteria. Studies were rated for evidential consideration as high,
      intermediate, or low based upon the study design, number of participants,
      exposure measurement, and neurodevelopmental measures. All but one of the 27
      studies evaluated showed some negative effects of pesticides on neurobehavioral
      development. A positive dose-response relationship between OP exposure and
      neurodevelopmental outcomes was found in all but one of the 12 studies that
      assessed dose-response. In the ten longitudinal studies that assessed prenatal
      exposure to OPs, cognitive deficits (related to working memory) were found in
      children at age 7 years, behavioral deficits (related to attention) seen mainly
      in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No
      meta-analysis was possible due to different measurements of exposure assessment
      and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were
      rated intermediate, and two studies were rated low. Evidence of neurological
      deficits associated with exposure to OP pesticides in children is growing. The
      studies reviewed collectively support the hypothesis that exposure to OP
      pesticides induces neurotoxic effects. Further research is needed to understand
      effects associated with exposure in critical windows of development. 

PMID- 24121007
TI  - Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR
      induced oxidative stress and apoptosis: role of Nrf2-dependent gene expression
      and antioxidant enzymes.
AB  - Chronic UVR-exposure may impair the stress response and antioxidant defense
      mechanisms of human skin. The transcription factor nuclear factor erythroid-2
      related factor 2 (Nrf2) orchestrates the expression of genes coding for the
      stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and
      phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced
      oxidative stress and apoptosis in ex vivo human full-thickness skin combined with
      in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction
      of genes coding for Nrf2-dependent phase II antioxidative enzymes (gamma
      glutamylcysteine-synthetase (gammaGCS), heme oxygenase 1 (HO-1) and NAD(P)H
      quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes.
      Comparative investigations in human ex vivo skin were conducted for analysis of
      gene expression of above mentioned phase II enzymes and catalase (CAT) as well as
      hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR
      exposure of human skin (300mJ/cm(2)) resulted in a significant time-dependent
      increase of the number of sunburn cells and caspase-3 activation as biomarkers of
      apoptosis for up to 48h (p<0.001) and induced a significant decrease of the
      antioxidant enzyme catalase (p<0.001). This was significantly counteracted by the
      pre-treatment of human skin with SFN and PEITC (5MUM and 10MUM). Mechanistic cell
      culture studies revealed SFN and PEITC to increase Nrf2 activity and Nrf2
      dependent gene expression (gammaGCS, HO-1, NQO1); this was paralleled in human
      full skin mRNA. In conclusion, the induction of Nrf2-dependent antioxidant
      pathways seems to be a potential mechanism by which SFN and PEITC protect against
      UVR-induced oxidative stress and apoptosis in human skin. 

PMID- 24121008
TI  - Effect of VGLUT inhibitors on glutamatergic synaptic transmission in the rodent
      hippocampus and prefrontal cortex.
AB  - Vesicular glutamate transporters (VGLUTs) are known to be important in the uptake
      of glutamate into vesicles in the presynaptic terminal; thereby playing a role in
      synaptic function. VGLUT dysfunction has also been suggested in neurological and
      psychiatric disorders such as epilepsy and schizophrenia. A number of compounds
      have been identified as VGLUT inhibitors; however, little is known as to how
      these compounds affect synaptic transmission. We therefore investigated the
      effects of structurally unrelated VGLUT inhibitors on synaptic transmission in
      the rodent hippocampus and prefrontal cortex. In the CA1 and dentate gyrus
      regions of the in vitro slice preparation of mouse hippocampus, AMPA receptor
      mediated field excitatory postsynaptic potentials (fEPSPs) were evoked in
      response to Schaffer collateral/commissural pathway stimulation. Application of
      the VGLUT inhibitors Rose Bengal (RB), Congo Red (CR) or Chicago Sky Blue 6B (CB)
      resulted in a concentration-related reduction of fEPSP amplitudes. RB (30MUM) or
      CB (300MUM) also depressed NMDA receptor-mediated responses in the CA1 region.
      The naturally occurring kynurenine Xanthurenic Acid (XA) is reported to be a
      VGLUT inhibitor. We found XA attenuated both AMPA and NMDA receptor-mediated
      synaptic transmission. The potency order of the VGLUT inhibitors was consistent
      with literature Ki values for VGLUT inhibition. Impaired glutamatergic
      neurotransmission is believed to contribute to schizophrenia, and VGLUTs have
      also been implicated in this disease. We therefore investigated the effect of
      VGLUT inhibition in the prefrontal cortex. Application of the VGLUT inhibitors RB
      or CB resulted in a concentration-dependent reduction in the amplitude of
      glutamate receptor-mediated fEPSPs recorded in layer V/VI in response to
      stimulation in the forceps minor. We conclude that VGLUT inhibitors can modulate
      glutamatergic synaptic transmission in the PFC and hippocampus. This could be
      important in the pathophysiology of nervous system disorders and might represent
      a target for developing novel pharmacological therapies. 

PMID- 24121009
TI  - Corneal biomechanical properties: precision and influence on tonometry.
AB  - PURPOSE: To assess the precision and reproducibility of the corneal biomechanical
      parameters, and their relationships with the intraocular pressure (IOP) measured
      with the Goldmann tonometer and a noncontact tonometer. METHODS: Readings for
      biomechanical properties and for IOP measured with the Goldmann and noncontact
      tonometers, were taken on one randomly selected eye of 106 normal subjects, on
      each one of two measurement sessions. Measurements with the ocular response
      analyzer (ORA) and the noncontact tonometer were randomized, followed by the
      measurement of central corneal thickness and with the Goldmann tonometer.
      RESULTS: Repeatability coefficients for CCT, corneal hysteresis (CH) and corneal
      resistance factor (CRF) in Session 1 were +/- 0.01 MUm, +/- 3.05 mmHg and +/-
      2.62 mmHg, respectively. The mean CCT, CH, CRF, Goldmann and noncontact tonometry
      did not vary significantly between sessions. Reproducibility coefficients for
      CCT, CH and CRF were +/- 0.02 MUm, +/- 2.19 mmHg and +/- 1.97 mmHg, respectively.
      Univariate regression analysis showed that CCT, CH and CRF significantly
      (P<0.0001) correlated with the IOP measured with the Goldmann and noncontact
      tonometers (and with the differences between tonometers) in Session 1. There were
      no significant correlations with the differences between tonometers in Session 2.
      Multivariate analysis revealed a minimal effect of CCT on Goldmann measurements
      but a significant effect on those of the noncontact tonometer. CONCLUSIONS:
      Measurement of the biomechanical properties of the cornea, using the ORA, are
      repeatable and reproducible, affect Goldmann tonometry less than noncontact
      tonometry, and have a minimal influence on the difference in measured intraocular
      pressure between tonometers.

PMID- 24121010
TI  - Preparation, characterization and antimicrobial study of a hydrogel (soft contact
      lens) material impregnated with silver nanoparticles.
AB  - PURPOSE: Contact lenses that incorporate antimicrobial properties may reduce the
      risk for microbial-associated adverse events for lens wearers. The aim of this
      study was to assess the antimicrobial effects of silver nanoparticles (NP) when
      impregnated in a hydrogel material. METHODS: Hydrogel disks, used as a proxy for
      soft contact lenses, were prepared with silver NPs to add an antimicrobial effect
      to the polymer. Six groups of disks were created, each with a different
      concentration of silver NPs. The antimicrobial effect of the hydrogels against
      Pseudomonas aeruginosa (ATCC15442) and Staphylococcus aureus (ATCC6538) was
      evaluated at 6, 24, 48 and 72 h. RESULTS: Silver NP concentrations ranged from
      20.71 to 98.06 MUg/disk. All groups demonstrated excellent antibacterial effects
      against P. aeruginosa at each time point. After 6h all disks didn't exhibit
      desirable antibacterial activity against S. aureus; whereas except those with
      20.71 MUg silver NPs showed antibacterial activity at 24h and only the disks with
      57.13 and 98.06 MUg silver NPs showed antimicrobial activity at 48 and 72 h.
      CONCLUSIONS: The development of contact lenses made of a silver NP-impregnated
      hydrogel material may bring antimicrobial effects sufficient to decrease the risk
      of microbial-related adverse events for lens wearers.

PMID- 24121011
TI  - Strategies for optimizing DNA hybridization on surfaces.
AB  - Specific and predictable hybridization of the polynucleotide sequences to their
      complementary counterparts plays a fundamental role in the rational design of new
      nucleic acid nanodevices. Generally, nucleic acid hybridization can be performed
      using two major strategies, namely hybridization of DNA or RNA targets to surface
      tethered oligonucleotide probes (solid-phase hybridization) and hybridization of
      the target nucleic acids to randomly distributed probes in solution (solution
      phase hybridization). Investigations into thermodynamic and kinetic parameters of
      these two strategies showed that hybridization on surfaces is less favorable than
      that of the same sequence in solution. Indeed, the efficiency of DNA
      hybridization on surfaces suffers from three constraints: (1) electrostatic
      repulsion between DNA strands on the surface, (2) steric hindrance between
      tethered DNA probes, and (3) nonspecific adsorption of the attached
      oligonucleotides to the solid surface. During recent years, several strategies
      have been developed to overcome the problems associated with DNA hybridization on
      surfaces. Optimizing the probe surface density, application of a linker between
      the solid surface and the DNA-recognizing sequence, optimizing the pH of DNA
      hybridization solutions, application of thiol reagents, and incorporation of a
      polyadenine block into the terminal end of the recognizing sequence are among the
      most important strategies for enhancing DNA hybridization on surfaces. 

PMID- 24121012
TI  - Competitive, immunometric assay for fusion protein quantification: protein
      production prioritization.
AB  - Effective drug discovery demands the availability of microgram to gram quantities
      of high-quality protein encoded by novel transcripts. Protein expression vectors
      designed for large-scale protein production often include one or more specific
      tags to such transcripts, to simplify the purification of the targeted protein.
      Optimization of the complex expression and purification process requires the
      evaluation of multiple expression candidate clones to identify a production
      suitable construct in terms of quality and final protein yield. Efficiency of the
      entire expression screening process is typically assessed by direct visualization
      of the banding patterns from whole-cell lysates on SDS-PAGE gels, by direct
      staining and/or immunoblotting, using antibodies against the tag or the protein
      of interest. These techniques, generally run under denaturing conditions, have
      proven to be only marginally predictive of the purification yield and authentic
      folding for native proteins. Small-scale, multiparallel affinity purification
      followed by SDS-PAGE analysis is more predictive for expression screening;
      however, this approach is labor intensive and time consuming. Here we describe
      the development of an alternative expression efficiency assessment technique,
      designed to evaluate the accessibility of affinity tags expressed with the
      desired fusion proteins, using acoustic membrane microparticle assay technology
      on the ViBE protein analysis workstation. 

PMID- 24121013
TI  - A plate-based high-throughput activity assay for polysialyltransferase from
      Neisseria meningitidis.
AB  - Polysialyltransferases (PSTs) assemble polysialic acid (PSA) and have been
      implicated in many biological processes. For example, certain bacteria such as
      neuroinvasive Neisseria meningitidis decorate themselves in a PSA capsule to
      evade the innate immune system. Identifying inhibitors of PSTs therefore
      represents an attractive therapeutic goal and herein we describe a high
      throughput, robust, and sensitive microtiter-plate-based activity assay for PST
      from N. meningitidis. A trisialyl lactoside (GT3) serving as the acceptor
      substrate was immobilized on a 384-well plate by click chemistry. Incubation with
      PST and CMP-sialic acid for 30min resulted in polysialylation. The immobilized
      PSA was then directly detected using a green fluorescent protein (GFP)-fused PSA
      binding protein consisting of the catalytically inactive double mutant of an
      endosialidase (GFP-EndoNF DM). We report very good agreement between kinetic and
      inhibition parameters obtained with our on-plate assay versus our in-solution
      validation assay. In addition we prove our assay is robust and reliable with a Z'
      score of 0.79. All aspects of our assay are easily scalable owing to optimization
      trials that allowed immobilization of acceptor substrates prepared from crude
      reaction mixtures and the use of cell lysates. This assay methodology enables
      large-scale PST inhibitor screens and can be harnessed for directed evolution
      screens. 

PMID- 24121014
TI  - Relationship between early changes in cerebral blood volume and electrocortical
      activity after hypoxic-ischemic insult in newborn piglets.
AB  - BACKGROUND: Early changes in cerebral hemodynamics and depressed electrocortical
      activity have been reported after a hypoxic-ischemic (HI) insult. However, the
      relationship between these two parameters is unclear. This study aimed to examine
      the relationship between changes in cerebral blood volume (CBV) and cerebral Hb
      oxygen saturation (ScO2) after a HI insult and the low amplitude-integrated
      electroencephalography (aEEG) duration concomitantly observed. METHODS: Sixteen
      newborn piglets obtained within 24h of birth were used (n=3 controls). Thirteen
      piglets were subjected to a HI insult of 20-min low-amplitude aEEG (<5 MUV,
      LAEEG), after which a low mean arterial blood pressure (<70% of baseline) was
      maintained for 10 min. We measured changes in CBV and ScO2 using near-infrared
      time-resolved spectroscopy (TRS) and cerebral electrocortical activities using
      aEEG until 6h after the insult. RESULTS: A positive correlation was observed
      between the LAEEG duration and CBV increase, but not ScO2, after the insult.
      CONCLUSION: These results suggest that a larger increase in CBV reflected a more
      severe failure in cerebral circulation to maintain cell membrane action
      potentials, which induced a more extended recovery period of electrocortical
      activity after the insult. We conclude that an early increase in CBV and longer
      LAEEG indicate severe brain injury.

PMID- 24121015
TI  - Cordycepin: a bioactive metabolite with therapeutic potential.
AB  - Cytotoxic nucleoside analogues were the first chemotherapeutic agents for cancer
      treatment. Cordycepin, an active ingredient of the insect fungus Cordyceps
      militaris, is a category of compounds that exhibit significant therapeutic
      potential. Cordycepin has many intracellular targets, including nucleic acid
      (DNA/RNA), apoptosis and cell cycle, etc. Investigations of the mechanism of anti
      cancer drugs have yielded important information for the design of novel drug
      targets in order to enhance anti-tumor activity with less toxicity to patients.
      This extensive review covers various molecular aspects of cordycepin interactions
      with its recognized cellular targets and proposes the development of novel
      therapeutic strategies for cancer treatment. 

PMID- 24121016
TI  - Computational and experimental analysis identified 6-diazo-5-oxonorleucine as a
      potential agent for treating infection by Plasmodium falciparum.
AB  - Plasmodium falciparum (PF) is the most severe malaria parasite. It is developing
      resistance quickly to existing drugs making it indispensable to discover new
      drugs. Effective drugs have been discovered targeting metabolic enzymes of the
      parasite. In order to predict new drug targets, computational methods can be used
      employing database information of metabolism. Using this data, we performed
      recently a computational network analysis of metabolism of PF. We analyzed the
      topology of the network to find reactions which are sensitive against
      perturbations, i.e., when a single enzyme is blocked by drugs. We now used a
      refined network comprising also the host enzymes which led to a refined set of
      the five targets glutamyl-tRNA (gln) amidotransferase, hydroxyethylthiazole
      kinase, deoxyribose-phophate aldolase, pseudouridylate synthase, and
      deoxyhypusine synthase. It was shown elsewhere that glutamyl-tRNA (gln)
      amidotransferase of other microorganisms can be inhibited by 6-diazo-5
      oxonorleucine. Performing a half maximal inhibitory concentration (IC50) assay,
      we showed, that 6-diazo-5-oxonorleucine is also severely affecting viability of
      PF in blood plasma of the human host. We confirmed this by an in vivo study
      observing Plasmodium berghei infected mice. 

PMID- 24121017
TI  - Infection of cats with atypical feline coronaviruses harbouring a truncated form
      of the canine type I non-structural ORF3 gene.
AB  - Feline and canine coronaviruses (FCoV and CCoV, respectively) are common
      pathogens of cats and dogs sometimes leading to lethal infections named feline
      infectious peritonitis (FIP) and canine pantropic coronavirus infection. FCoV and
      CCoV are each subdivided into two serotypes, FCoV-I/II and CCoV-I/II. A
      phylogenetic relationship is evident between, on one hand, CCoV-I/FCoV-I, and on
      the other hand, CCoV-II/FCoV-II, suggesting that interspecies transmission can
      occur. The aim of the present study was to evaluate the prevalence of coronavirus
      (CoV)-infected cats according to their contact with dogs and to genetically
      analyse the CoV strains infecting cats. From 2003 to 2009, we collected 88 faecal
      samples from healthy cats and 11 ascitic fluids from FIP cats. We investigated
      the possible contact with dog in the household and collected dogs samples if
      appropriate. Out of 99 cat samples, 26 were coronavirus positive, with six cats
      living with at least one dog, thus showing that contact with dogs does not appear
      as a predisposing factor for cats CoV infections. Molecular and phylogenetic
      analyses of FCoV strains were conducted using partial N and S sequences. Six
      divergent strains were identified with the N gene clustering with CCoV-I whereas
      the 3' end of S was related to FCoV-I. Further analysis on those six samples was
      attempted by researching the presence of the ORF3 gene, the latter being peculiar
      to CCoV-I to date. We succeeded to amplify the ORF3 gene in five samples out of
      six. Thus, our data strongly suggest the circulation of atypical FCoV strains
      harbouring the CCoV-I ORF3 gene among cats. Moreover, the ORF3 genes recovered
      from the feline strains exhibited shared deletions, never described before,
      suggesting that these deletions could be critical in the adaptation of these
      strains to the feline host. 

PMID- 24121018
TI  - Human insulin does not increase prostate cancer risk in Taiwanese.
AB  - BACKGROUND: Whether human insulin can increase the risk of prostate cancer is
      rarely studied. PATIENTS AND METHODS: The reimbursement databases of all
      Taiwanese patients with diabetes from 1996 to 2009 were retrieved from the
      National Health Insurance databases of Taiwan. An entry date was set at January
      1, 2004 and a total of 498,407 men with type 2 diabetes were followed for
      prostate cancer incidence until the end of 2009. Incidence for ever-users, never
      users, and subgroups of human insulin exposure (using tertile cutoffs of time
      since starting insulin, cumulative dose, and cumulative duration of insulin) were
      calculated, and the age-adjusted and multivariable-adjusted hazard ratios were
      estimated using Cox regression. RESULTS: There were 72,948 ever-users and 425,459
      never-users, with respective numbers of incident prostate cancer of 768 (1.05%)
      and 6282 (1.48%), and respective incidence of 236.87 and 276.88 per 100,000
      person-years. The overall hazard ratios (95% confidence intervals) indicated a
      significant negative association with insulin in the age-adjusted model (0.910;
      0.843-0.981), but lack of association in the full model adjusted for
      multivariables (0.989; 0.912-1.072). The hazard ratios for the different
      categories of the dose-responsive parameters might show significantly lower risk
      with insulin use in the age-adjusted models, but none of the hazard ratios were
      significant in the full models. CONCLUSION: This study suggests a lack of
      association between the use of human insulin and prostatic cancer risk in
      patients with type 2 diabetes after multivariable adjustment.

PMID- 24121019
TI  - IFN-gamma-driven intratumoral microenvironment exhibits superior prognostic
      effect compared with an IFN-alpha-driven microenvironment in patients with colon
      carcinoma.
AB  - Interferon (IFN)-alpha and IFN-gamma are cytokines with potent immunomodulating
      and anti-tumor activities. It is unknown which of the two IFNs may be more potent
      in the regulation of an anti-tumorigenic response in colorectal carcinoma or
      whether both cytokines cooperate. We, therefore, established human myxovirus
      resistance protein A and human guanylate-binding protein-1 as markers for the
      differential detection of IFN-alpha- and IFN-gamma-driven tumor micromilieus,
      respectively. In vitro studies with different cultures of tumor cells from
      colorectal carcinoma and stroma cells showed that the expression of myxovirus
      resistance protein A was exclusively induced by IFN-alpha, whereas guanylate
      binding protein-1 was strongly induced by IFN-gamma and only weakly by IFN-alpha.
      This expression pattern was used to distinguish cell activation caused by the two
      cytokines in a clinical cohort of patients with colon carcinoma (n = 378).
      Patients with primary tumors expressing only guanylate-binding protein-1
      exhibited the highest cancer-specific 5-year survival (94.0%, P = 0.006) compared
      with those expressing both factors (90.3%, P = 0.006), myxovirus resistance
      protein A alone (83.5%, P = 0.096), or none (72.8%). Our study describes a
      successful proof-of-principle approach that complex cytokine interaction networks
      can be dissected in human tissues and demonstrates that an IFN-gamma-driven tumor
      microenvironment exhibits a superior prognostic effect compared with an IFN-alpha
      driven tumor microenvironment in colon carcinoma.

PMID- 24121020
TI  - TNF-alpha modulation of intestinal epithelial tight junction barrier is regulated
      by ERK1/2 activation of Elk-1.
AB  - Tumor necrosis factor (TNF-alpha) is a proinflammatory cytokine that plays a
      critical role in the pathogenesis of inflammatory bowel disease. TNF-alpha causes
      an increase in intestinal permeability; however, the signaling pathways and the
      molecular mechanisms involved remain unclear. The major purpose of this study was
      to investigate the role of MAP kinase pathways (ERK1/2 and p38 kinase) and the
      molecular processes involved. An in vitro intestinal epithelial model system
      consisting of Caco-2 monolayers and an in vivo mouse model system were used to
      delineate the cellular and molecular mechanisms involved in TNF-alpha effects on
      tight junction barrier. The TNF-alpha-induced increase in Caco-2 tight junction
      permeability was mediated by activation of the ERK1/2 signaling pathway, but not
      the p38 kinase pathway. Activation of the ERK1/2 pathway led to phosphorylation
      and activation of the ETS domain-containing transcription factor Elk-1. The
      activated Elk-1 translocated to the nucleus, where it bound to its binding motif
      on the myosin light chain kinase (MLCK) promoter region, leading to the
      activation of MLCK promoter activity and gene transcription. In addition, in vivo
      intestinal perfusion studies also indicated that the TNF-alpha-induced increase
      in mouse intestinal permeability requires ERK1/2-dependent activation of Elk-1.
      These studies provide novel insight into the cellular and molecular processes
      that regulate the TNF-alpha-induced increase in intestinal epithelial tight
      junction permeability.

PMID- 24121021
TI  - Postmortem heart weight: relation to body size and effects of cardiovascular
      disease and cancer.
AB  - BACKGROUND: Gender, body weight, and cardiovascular disease (CVD) are all
      variables known to influence human heart weight. The impact of cancer is less
      studied, and the influence of age is not unequivocal. We aimed to describe the
      relationship between body size and heart weight in a large autopsy cohort and to
      compare heart weight in patients with cancer, CVD, and other diseases. METHODS
      AND RESULTS: Registered information, including cause of death, evidence of cancer
      and/or CVD, heart weight, body weight, and height, was extracted from the autopsy
      reports of 1410 persons (805 men, mean age 66.5 years and 605 women, mean age
      70.6 years). The study population was divided in four groups according to cause
      of death; cancer (n=349), CVD (n=470), mixed group who died from cancer and CVD
      and/or lung disease (n=263), and a reference group with patients who did not die
      from any of these conditions (n=328). In this last group, heart weight correlated
      only slightly better with body surface area than body weight, and nomograms based
      on body weight are presented. Compared to the reference group (mean heart weight:
      426 g and 351 g in men and women, respectively), heart weight was significantly
      lower (men: P<.05, women: P<.001) in cancer patients (men: 392 g, women: 309 g)
      and higher (P<.001) in patients who died from CVD (men: 550 g, women: 430 g).
      Similar results were obtained in linear regression models adjusted for body
      weight and age. Among CVD, heart valve disease had the greatest impact on heart
      weight, followed by old myocardial infarction, coronary atherosclerosis, and
      hypertension. Absolute heart weight decreased with age, but we demonstrated an
      increase relative to body weight. CONCLUSION: The weight of the human heart is
      influenced by various disease processes, in addition to body weight, gender, and
      age. While the most prevalent types of CVD are associated with increased heart
      weight, patients who die from cancer have lower average heart weight than other
      patient groups. The latter finding, however, is diminished when adjusting for
      body weight. SUMMARY: The present study demonstrates that the weight of the human
      heart is influenced by various disease processes like cancer and CVD, in addition
      to body weight, gender and, possibly, age.

PMID- 24121022
TI  - Revealing natural antisense transcripts from Plasmodium vivax isolates: evidence
      of genome regulation in complicated malaria.
AB  - Plasmodium vivax is the most geographically widespread human malaria parasite
      causing approximately 130-435 million infections annually. It is an economic
      burden in many parts of the world and poses a public health challenge along with
      the other Plasmodium sp. The biology of this parasite is less studied and poorly
      understood, in spite of these facts. Emerging evidence of severe complications
      due to infections by this parasite provides an impetus to focus research on the
      same. Investigating the parasite directly from infected patients is the best way
      to study its biology and pathogenic mechanisms. Gene expression studies of this
      parasite directly obtained from the patients has provided evidence of gene
      regulation resulting in varying amount of transcript levels in the different
      blood stages. The mechanisms regulating gene expression in malaria parasites are
      not well understood. Discovery of Natural Antisense Transcripts (NATs) in
      Plasmodium falciparum has suggested that these might play an important role in
      regulating gene expression. We report here the genome-wide occurrence of NATs in
      P. vivax parasites from patients with differing clinical symptoms. A total of
      1348 NATs against annotated gene loci have been detected using a custom designed
      microarray with strand specific probes. Majority of NATs identified from this
      study shows positive correlation with the expression pattern of the sense (S)
      transcript. Our data also shows condition specific expression patterns of varying
      S and antisense (AS) transcript levels. Genes with AS transcripts enrich to
      various biological processes. To our knowledge this is the first report on the
      presence of NATs from P. vivax obtained from infected patients with different
      disease complications. The data suggests differential regulation of gene
      expression in diverse clinical conditions, as shown by differing sense/antisense
      ratios and would lead to future detailed investigations of gene regulation.

PMID- 24121023
TI  - Emergence of Acinetobacter baumannii international clone II in Brazil: reflection
      of a global expansion.
AB  - The aim of this study was to investigate the occurrence of carbapenem-resistant
      Acinetobacter baumannii international clones (IC) in Curitiba, Brazil, using
      multilocus sequence typing and trilocus PCR-based typing schemes. IC2 was the
      first emerging clone. This IC was detected in an isolate from 2003 of a PFGE type
      spread in at least two hospitals since 1999. Subsequently, IC2 waned while IC1
      and clonal complex 15/104 prevailed. This is the first description of IC2 in
      Brazil and Latin America. 

PMID- 24121024
TI  - Understanding response and resistance to oestrogen deprivation in ER-positive
      breast cancer.
AB  - Oestrogens (E) and oestrogen receptor alpha (ERalpha) play fundamental roles in
      the development and progression of more than three-quarters of breast cancers
      (BC). The ability to influence the natural history of BC by hormonal manipulation
      is well established and endocrine therapies represent the cornerstone of systemic
      management for women with ERalpha-positive disease. Endocrine agents abrogate
      oestrogenic signalling through distinct and incompletely overlapping mechanisms,
      either impeding the transcriptional activity of ERalpha or diminishing E
      synthesis. In post-menopausal women, E-production is chiefly attributable to the
      enzymatic conversion of androgens in extra-gonadal tissues by the cytochrome P
      450 superfamily member aromatase. Greater understanding of steroid biosynthesis
      has underpinned rational drug design and pharmacological development of potent
      and specific aromatase inhibitors (AIs). Contemporary agents induce profound E
      suppression in post-menopausal women and are first-line neo-adjuvant, adjuvant
      and metastatic therapies, with greater efficacy and tolerability than tamoxifen.
      The principal qualifier for endocrine treatment, including AIs, remains ERalpha
      expression. However, it is increasingly apparent that ERalpha expression is not
      synonymous with sensitivity to treatment and insufficient to account for the
      considerable heterogeneity of response. Better predictive biomarkers of de novo
      resistance are required to improve patient selection and identify those poor
      responders who may benefit from alternative or additional systemic treatment from
      the outset. Among patients who do respond well initially, many relapse during
      their clinical course and there is also an unmet need for biomarkers of acquired
      resistance. The majority of women who relapse on AIs continue to express
      functional ERalpha which remains a legitimate target for second-line endocrine
      therapy. Understanding and overcoming acquired resistance to AIs requires a
      greater appreciation of ERalpha biology and the mechanisms though which E
      dependence can be subverted. In this article, we review the impact of therapeutic
      E-deprivation on the natural history of ERalpha-positive breast cancer.
      Consideration is given to established and emerging biomarkers and/or determinants
      of response and resistance to E-deprivation. In vitro and in vivo evidence of the
      molecular mechanisms underpinning the transition from sensitivity to resistance
      are reviewed in the context of current models of ERalpha activity and their
      potential translational relevance. 

PMID- 24121025
TI  - Ovariectomy and 17beta-estradiol replacement play a role on the expression of
      Endonuclease-G and phosphorylated cyclic AMP response element-binding (CREB)
      protein in hippocampus.
AB  - The aim of the present study was to investigate the effects of different periods
      of ovariectomy and 17beta-estradiol (E2) replacement on the expression of
      Cytochrome C, apoptosis inducing factor (AIF) and Endonuclease-G (Endo-G) in
      mitochondrial and cytosolic fractions obtained from hippocampus of the adult
      female rats. In addition, the expression of phosphorylated CREB (phospho-CREB)
      was also analyzed in hippocampus. Ovariectomy or E2 treatment did not change the
      expression of Cytochrome C and AIF. Ovariectomy (15, 21 and 36 days) decreased
      the expression of Endo-G in the mitochondrial fractions and increased it in the
      cytosolic fractions obtained from hippocampus. The treatment with E2 after 15
      days of ovariectomy for 7 days or 21 days, and throughout the post-ovariectomy
      period prevented the effects of ovariectomy on Endo-G expression. Our results
      suggest that ovariectomy-induced apoptotic cell death in hippocampal tissue could
      be mediated by Endo-G, but not by AIF, via a caspase-independent apoptotic
      pathway. Furthermore, ovariectomy decreased the expression of phospho-CREB and
      the treatment with E2 prevented these effects. In conclusion, E2 may help
      maintain long-term neuronal viability by regulating the expression of members of
      the Bcl-2 family. Regulation of Endo-G released from mitochondria, but not of
      Cytochrome C and AIF, is also involved in the neuroprotective actions of E2.
      Furthermore, CREB may be involved in the expression of Bcl-2. These data provide
      new understanding into the mechanisms involved in the neuroprotective role of
      estrogen.

PMID- 24121026
TI  - T3 enhances thyroid cancer cell proliferation through TRbeta1/Oct-1-mediated
      cyclin D1 activation.
AB  - Several studies have demonstrated that thyroid hormone T3 promotes cancer cell
      growth, even though the molecular mechanism involved in such processes still
      needs to be elucidated. In this study we demonstrated that T3 induced
      proliferation in papillary thyroid carcinoma cell lines concomitantly with an up
      regulation of cyclin D1 expression, that is a critical mitogen-regulated cell
      cycle control element. Our data revealed that T3 enhanced the recruitment of the
      TRbeta1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1
      promoter, leading to its transactivation. In addition, silencing of TRbeta1 or
      Oct-1 expression by RNA interference reversed both increased cell proliferation
      and up-regulation of cyclin D1, underlying the important role of both
      transcriptional factors in mediating these effects. Finally, T3-induced increase
      in cell growth was abrogated after knocking down cyclin D1 expression. All these
      findings highlight a new molecular mechanism by which T3 promotes thyroid cancer
      cell growth. 

PMID- 24121027
TI  - Medial prefrontal cortex dissociation between self and others in a referential
      task: an fMRI study based on word traits.
AB  - A number of recent neuroimaging studies using self referential tasks have
      investigated whether self referential processing depends on a unique neural basis
      that operates specifically in the medial prefrontal cortex. However, these
      studies have provided contradictory results despite the use of similar
      methodologies. We hypothesized that these discrepancies are partially related to
      the task-difficulty that presents dissociations reaction times in the self- and
      other-referential tasks. We therefore measured brain activity during self and
      other referential tasks to determine if such activity can be dissociated
      according to the reaction times (fast versus slow) for the trait words.
      Activation differed across self and other only in the slow word condition. The
      self referential condition with slow reaction time produced greater activation in
      the ventromedial prefrontal cortex, whereas the other referential condition with
      slow reaction time produced activation of the middle temporal gyrus. Results
      suggested that the task-difficulty might affect whether or not brain activities
      within MPFC would be dissociated between self- and other-referential processing. 

PMID- 24121028
TI  - Post hoc power calculations and statistical analysis of case control studies:
      reply to Riboldi et al.

PMID- 24121030
TI  - Peptidoglycan hydrolases, bacterial shape, and pathogenesis.
AB  - Bacterial shape has always been hypothesized to play an important role in the
      biology of a species and in the ability of certain bacteria to influence human
      health. The recent discovery of peptidoglycan hydrolases that modulate shape has
      now allowed this hypothesis to be addressed directly. Genetic, biochemical, and
      phenotypic studies have found that changes in shape and underlying peptidoglycan
      structure influence many pathogenic attributes including surviving unfavorable
      conditions, predation, transmission, colonization, and host interactions. The
      diversity of bacterial shapes, niches, and lifestyles is also reflected in
      diverse mechanisms of hydrolase regulation, critical for maintaining
      peptidoglycan integrity and biological properties of the cell. Future studies
      will build on the current work described and further elucidate the intersection
      of peptidoglycan hydrolase activity, shape, and disease outcome. 

PMID- 24121029
TI  - Candida albicans specializations for iron homeostasis: from commensalism to
      virulence.
AB  - Candida albicans is a fungal commensal-pathogen that persistently associates with
      its mammalian hosts. Between the commensal and pathogenic lifestyles, this
      microorganism inhabits host niches that differ markedly in the levels of
      bioavailable iron. A number of recent studies have exposed C. albicans
      specializations for acquiring iron from specific host molecules in regions where
      iron is scarce, while also defending against iron-related toxicity in regions
      where iron occurs in surfeit. Together, these results point to a central role for
      iron homeostasis in the evolution of this important human pathogen. 

PMID- 24121031
TI  - Annexin A5 as a potential marker in tumors.
AB  - Annexin A5 (Anxa5) promotes pancreatic adenocarcinoma, sarcoma, tumorigenesis and
      progression of breast cancer and prostate cancer stem cells. It is involved with
      metastasis, invasion and development of squamous cell carcinoma, and facilitates
      nodal progression of bladder cancer and angiogenesis and progression of glioma.
      Anxa5 de-regulation is associated with drug resistance in nasopharyngeal
      carcinoma and gastric cancer. Although Anxa5 protein up-regulation promotes
      cervical cancer progression, it is markedly suppressed in cervical carcinoma
      cells. Anxa5 is negatively correlated with thyroid cancer malignancy. In this
      review, we explore the mechanisms of Anxa5 action in tumors. Anxa5 could be a
      predictive biomarker for tumor development, metastasis and invasion, and be of
      diagnostic, prognostic and therapeutic significance in cancer. 

PMID- 24121032
TI  - Lab Tests Online and consumer understanding of laboratory testing.
AB  - Lab Tests Online is a "peer-reviewed, non-commercial, patient-centered" resource
      where patients and their relatives and caregivers can learn about the tests used
      to screen for, diagnose, and manage disease. Consumers are becoming increasingly
      involved in the management of their own health care and increasingly have access
      to their laboratory results through electronic health records. Research has shown
      that consumers have difficulty with health literacy in general and with numerical
      data in particular. The Lab Tests Online global websites are an important step
      toward helping consumers understand the complexity of the pathology process, the
      expertise of the people involved and the meaning of the results provided to them
      and their healthcare professionals.

PMID- 24121033
TI  - Severe preeclampsia: are hemostatic and inflammatory parameters associated?
AB  - BACKGROUND: Preeclampsia (PE) is characterized by hypertension and proteinuria. A
      predisposition to endothelial dysfunction, which may trigger abnormal activation
      of the hemostatic and/or inflammatory systems, is thought to play a crucial part
      in pathogenesis of PE. We investigated the relationship between hemostatic and
      inflammatory parameters in women with severe PE. METHODS: D-Dimer, PAI-1, IL-8,
      IL-6, TNF-alpha, and IFN-gamma concentrations were measured in 59 pregnant women
      with severe PE (sPE), 49 normotensive pregnant and 48 non-pregnant women.
      RESULTS: D-Dimer and PAI-1 were higher in women with sPE compared to normotensive
      pregnant and non-pregnant women. IL-8, IL-6, and IFN-gamma also were higher in
      women with sPE compared to normotensive pregnant women. However, only IL-6 and
      IFN-gamma were higher in women with sPE compared to non-pregnant women. Moreover,
      D-Dimer and PAI-1 showed an elevated area under ROC curve proving to be excellent
      for discriminating sPE. Correlation analysis showed a weak correlation between D
      Dimer and IL-8 and between PAI-1 and IFN-gamma in sPE. CONCLUSION: D-Di and PAI-1
      concentrations showed to be an important tool for monitoring sPE.

PMID- 24121035
TI  - The inhibitory effect of sleep deprivation on cell proliferation in the
      hippocampus of adult mice is eliminated by corticosterone clamp combined with
      interleukin-1 receptor 1 knockout.
AB  - Deprivation or fragmentation of sleep for longer than 2days significantly
      inhibits cell proliferation and neurogenesis in the hippocampus of adult rats and
      mice. Signaling pathways that mediate these effects have yet to be clarified.
      Although deprivation procedures can stimulate adrenal corticosterone (CORT)
      release, suppression of cell proliferation by sleep deprivation does not require
      elevated CORT. We examined a role for interleukin-1beta (IL-1beta), a pro
      inflammatory cytokine that is increased by sleep loss and that mediates effects
      of stress on hippocampal neurogenesis. Wild type (WT) and IL-1 receptor 1
      knockout (IL1RI-KO) mice were subjected to rapid-eye-movement sleep deprivation
      (RSD) for 72-h using the multiple platform-over-water method. Mice were
      administered BrdU (100mg/kg) i.p. at hour 70 of RSD and were sacrificed 2-h
      later. New cells were identified by immunoreactivity (ir) for BrdU and Ki67 in
      the granular cell layer/subgranular zone (GCL/SGZ) and the hilus. In Experiment
      1, WT and IL1RI-KO mice, by contrast with respective control groups, exhibited
      significantly fewer BrdU-ir and Ki67-ir cells. In Experiment 2, WT and IL1RI-KO
      mice were adrenalectomized (ADX) and maintained on constant low-dose CORT by
      osmotic minipumps. RSD reduced cell proliferation by 32% (p<0.01) in ADX-WT
      animals but did not significantly reduce proliferation in ADX IL1RI-KO animals
      (p>0.1). These results imply that RSD suppresses cell proliferation by the
      presence of wake-dependent factors (either elevated CORT or IL-1beta signaling
      are sufficient), rather than the absence of a REM sleep-dependent process. The
      generality of these findings to other sleep deprivation methods and durations
      remains to be established. 

PMID- 24121036
TI  - Editorial comment.

PMID- 24121034
TI  - Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at
      the cutting edge of antiviral research.
AB  - The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic
      transmission of animal coronaviruses (CoV) to humans poses a significant threat
      to public health and warrants surveillance and the development of
      countermeasures. The activity of host cell proteases, which cleave and activate
      the SARS-CoV spike (S) protein, is essential for viral infectivity and
      constitutes a target for intervention. However, the identities of the proteases
      involved have been unclear. Pioneer studies identified cathepsins and type II
      transmembrane serine proteases as cellular activators of SARS-CoV and
      demonstrated that several emerging viruses might exploit these enzymes to promote
      their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV
      for S protein activation, we will discuss their contribution to viral spread in
      the host and we will outline antiviral strategies targeting these enzymes. This
      paper forms part of a series of invited articles in Antiviral Research on "From
      SARS to MERS: 10years of research on highly pathogenic human coronaviruses.'' 

PMID- 24121039
TI  - Cryo FIB-SEM: volume imaging of cellular ultrastructure in native frozen
      specimens.
AB  - Volume microscopy at high resolution is increasingly required to better
      understand cellular functions in the context of three-dimensional assemblies.
      Focused ion beam (FIB) milling for serial block face imaging in the scanning
      electron microscope (SEM) is an efficient and fast method to generate such volume
      data for 3D analysis. Here, we apply this technique at cryo-conditions to image
      fully hydrated frozen specimen of mouse optic nerves and Bacillus subtilis spores
      obtained by high-pressure freezing (HPF). We established imaging conditions to
      directly visualize the ultrastructure in the block face at -150  degrees C by
      using an in-lens secondary electron (SE) detector. By serial sectioning with a
      focused ion beam and block face imaging of the optic nerve we obtained a volume
      as large as X=7.72 MUm, Y=5.79 MUm and Z=3.81 MUm with a lateral pixel size of
      7.5 nm and a slice thickness of 30 nm in Z. The intrinsic contrast of membranes
      was sufficient to distinguish structures like Golgi cisternae, vesicles,
      endoplasmic reticulum and cristae within mitochondria and allowed for a three
      dimensional reconstruction of different types of mitochondria within an
      oligodendrocyte and an astrocytic process. Applying this technique to dormant B.
      subtilis spores we obtained volumes containing numerous spores and discovered a
      bright signal in the core, which cannot be related to any known structure so far.
      In summary, we describe the use of cryo FIB-SEM as a tool for direct and fast 3D
      cryo-imaging of large native frozen samples including tissues.

PMID- 24121038
TI  - The production of reactive oxygen species in TLR-stimulated granulocytes is not
      enhanced by hyperglycemia in diabetes.
AB  - Toll-like receptors (TLRs) play an important role in several inflammatory
      diseases such as diabetes. The present study was to determine whether
      hyperglycemia in diabetes interferes in reactive oxygen species (ROS) production
      in granulocytes stimulated with either TLR2/zymosan, TLR4/lipopolysaccharide
      (LPS) or TLR2,4,9/concanavalin A (ConA). NADPH (nicotinamide adenine dinucleotide
      phosphate) oxidase and mitogen-activated protein kinase (MAPK) signaling pathways
      associated with ROS generation in TLR-stimulated granulocytes were evaluated. Our
      results demonstrate that ROS generation in resting granulocytes derived from
      patients suffering from Type 2 diabetes mellitus (T2DM) is significantly higher
      than that observed in equivalent cells from healthy controls. However, ROS formed
      by TLR-stimulated granulocytes from T2DM patients and healthy subjects were
      comparable. ROS production by TLR4,9 depends on NADPH-oxidase and MAPK signaling
      pathways. In contrast, the activation of TLR2 leads to ROS production by a
      mechanism that is dependent on NADPH oxidase but independent of the MAPK. In
      conclusion our results suggest that hyperglycemia in diabetes may prime cells
      metabolically for ROS generation but does not exert any significant effect on TLR
      stimulated ROS production and possibly does not aggravate the development of ROS
      dependent diabetic complications. 

PMID- 24121037
TI  - Cellular and urinary microRNA alterations in NZB/W mice with hydroxychloroquine
      or prednisone treatment.
AB  - Determining alterations to disease-associated miRNAs induced by specific
      therapeutics may allow the use of tailored therapy in lupus. We determined miRNA
      alterations in female NZB/W lupus mice treated with hydroxychloroquine (HCQ) or
      prednisone (PRED) for 12 weeks beginning at 24 weeks-of-age. B cell, PBMC, and
      urinary miR-let-7a expression were decreased with HCQ or PRED treatment. HCQ or
      PRED treatment reduced miR-21 expression in mesangial cells, T cells, pDCs,
      PBMCs, and the urine. MiR-146a expression was reduced in mesangial cells with HCQ
      treatment and in pDCs with HCQ or PRED treatment. PRED treatment increased miR
      155 expression in mesangial, B, and T cells and PBMCs yet decreased miR-155
      expression in pDCs and the urine. In vitro studies confirmed that HCQ or PRED's
      anti-inflammatory actions are dependent on their ability to inhibit miRNA
      expression. Our studies indicate that lupus therapeutics may work, in part, by
      altering the expression of disease-associated miRNAs.

PMID- 24121040
TI  - Optimization methods for decision making in disease prevention and epidemic
      control.
AB  - This paper investigates problems of disease prevention and epidemic control
      (DPEC), in which we optimize two sets of decisions: (i) vaccinating individuals
      and (ii) closing locations, given respective budgets with the goal of minimizing
      the expected number of infected individuals after intervention. The spread of
      diseases is inherently stochastic due to the uncertainty about disease
      transmission and human interaction. We use a bipartite graph to represent
      individuals' propensities of visiting a set of location, and formulate two
      integer nonlinear programming models to optimize choices of individuals to
      vaccinate and locations to close. Our first model assumes that if a location is
      closed, its visitors stay in a safe location and will not visit other locations.
      Our second model incorporates compensatory behavior by assuming multiple
      behavioral groups, always visiting the most preferred locations that remain open.
      The paper develops algorithms based on a greedy strategy, dynamic programming,
      and integer programming, and compares the computational efficacy and solution
      quality. We test problem instances derived from daily behavior patterns of 100
      randomly chosen individuals (corresponding to 195 locations) in Portland, Oregon,
      and provide policy insights regarding the use of the two DPEC models. 

PMID- 24121041
TI  - Circulating IL-35 in pancreatic ductal adenocarcinoma patients.
AB  - IL-35 is a novel inhibitory cytokine that is mainly produced by regulatory T
      cells (Tregs) and is required for Treg-mediated immunosuppression. However, the
      plasma levels of IL-35 in patients with pancreatic ductal adenocarcinoma (PDAC)
      have never been investigated. In this study, we found that plasma IL-35 levels
      more significantly increased in PDAC patients than in normal controls (134.53 +/-
      92.45 pg/mL vs. 14.26 +/- 6.56 pg/mL). IL-35 mRNA levels were positively
      correlated with plasma IL-35 levels (EBI3, R = 0.925, p<0.01; p35, R = 0.916,
      p<0.01). Furthermore, IL-35 expression levels were associated with lymph node
      metastasis (p = 0.001) and late tumor stage (p = 0.002). For the resected
      patients, high IL-35 expression levels were associated with large tumor size
      (p<0.01), higher TNM classification T staging (p<0.05), and late tumor stage
      (p<0.05). In conclusion, circulating IL-35 in PDAC patients significantly
      increased, suggesting that regulating the expression of IL-35 may provide a new
      possible target for the treatment of PDAC patients, especially for the resectable
      ones.

PMID- 24121042
TI  - Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to
      infliximab.
AB  - Infliximab (IFX) is a valid treatment for Crohn's disease (CD), but a relevant
      percentage of patients do not benefit from this therapy. In the Japanese
      population, the response to IFX was associated with markers in the TNF receptor
      superfamily 1A (TNFRSF1A) and 1B (TNFRSF1B) genes. We aimed to replicate the
      association previously described in the Japanese population and to ascertain the
      role of TNF receptors as modulators of the response to IFX. We studied 297 white
      Spanish CD patients with a known response to IFX: 238 responders and 59 primary
      nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed:
      rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B.
      Comparisons between groups were performed with chi-square tests or the Fisher's
      exact test. Different features (sex, age, disease duration, smoking among others)
      were evaluated as possible confounding factors. No significant association was
      found between the studied TNFRSF1A polymorphisms and response to IFX. In the
      TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in
      nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09-2.90; and an increased frequency
      of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs
      nonresponders and p = 0.023 vs patients with a partial response. Our results
      support a role of TNFRSF1B gene variants in the response to IFX in CD patients.

PMID- 24121044
TI  - Multitasking attractor networks with neuronal threshold noise.
AB  - We consider the multitasking associative network in the low-storage limit and we
      study its phase diagram with respect to the noise level T and the degree d of
      dilution in pattern entries. We find that the system is characterized by a rich
      variety of stable states, including pure states, parallel retrieval states,
      hierarchically organized states and symmetric mixtures (remarkably, both even and
      odd), whose complexity increases as the number of patterns P grows. The analysis
      is performed both analytically and numerically: Exploiting techniques based on
      partial differential equations, we are able to get the self-consistencies for the
      order parameters. Such self-consistency equations are then solved and the
      solutions are further checked through stability theory to catalog their
      organizations into the phase diagram, which is outlined at the end. This is a
      further step towards the understanding of spontaneous parallel processing in
      associative networks. 

PMID- 24121043
TI  - Aspartate aminotransferase: an old dog teaches new tricks.
AB  - Aspartate aminotransferase (AAT) is a prototypical pyridoxal 5'-phosphate (PLP)
      dependent enzyme that catalyzes the reversible interconversion of l-aspartate and
      alpha-ketoglutarate with oxalacetate and l-glutamate via a ping-pong catalytic
      cycle in which the pyridoxamine 5'-phosphate enzyme form is an intermediate.
      There is a bountiful literature on AAT that spans approximately 60years, and much
      fundamental mechanistic information on PLP dependent reactions has been gained
      from its study. Here, we review our recent work on AAT, where we again used it as
      a test bed for fundamental concepts in PLP chemistry. First, we discuss the role
      that coenzyme protonation state plays in controlling reaction specificity, then
      ground state destabilization via hyperconjugation in the external aldimine
      intermediate is examined. The third topic is light enhancement of catalysis of
      Calpha-H deprotonation by PLP in solution and in AAT, which occurs through a
      triplet state of the external aldimine intermediate. Lastly, we consider recent
      advances in our analyses of enzyme multiple sequence alignments for the purpose
      of predicting mutations that are required to interconvert structurally similar
      but catalytically distinct enzymes, and the application of our program JANUS to
      the conversion of AAT into tyrosine aminotransferase. 

PMID- 24121045
TI  - Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced
      mechanical dysfunction and cell death in isolated cardiomyocytes.
AB  - Contractile dysfunction and subsequent development of cardiomyopathies are well
      known limiting factors in the treatment of cancer with doxorubicin and have been
      linked to mitochondrial dysfunction. Here, using adult isolated paced
      cardiomyocytes, we have demonstrated that ligands of translocator protein (TSPO)
      4'-chlorodiazepam and TRO40303 prevented the doxorubicin-induced alterations in
      contractility and improved cardiomyocyte viability. This cardioprotective effect
      was closely associated with both a potent reduction in reactive oxygen species
      production and inhibition of mitochondrial permeability transition pore opening.
      Thus, preventive administration of TSPO ligands may represent a novel
      pharmacological strategy to protect the heart during doxorubicin treatment. 

PMID- 24121046
TI  - FDG-PET/CT in patients with ANCA-associated vasculitis: case-series and
      literature review.
AB  - OBJECTIVES: We aimed to assess the clinical value of FDG-PET/CT in patients with
      ANCA-associated vasculitis. MATERIALS AND METHODS: We retrospectively included 16
      patients with ANCA-associated vasculitis who underwent 21 FDG-PET/CT between 2009
      and 2013, in 2 university hospitals from the Paris suburb area. All FDG-PET/CTs
      were retrospectively analyzed and compared to clinical, biological and
      conventional imaging data at baseline and during the follow-up. RESULTS: ANCA
      associated vasculitis was granulomatosis with polyangiitis (GPA, n=10),
      microscopic polyangiitis (MPA, n=4), and eosinophilic GPA (EGPA, n=2). PET was
      performed at initial presentation in 14 cases and during the follow-up in 7
      cases. At baseline, PET was positive in 100% of GPA patients (8/8) and in 50%
      (3/6) of patients with other ANCA-vasculitis (p=0.05). FDG uptake tended to be
      higher in patients with GPA in comparison to patients with MPA/EGPA (median
      SUVmax: 5 versus 2.5; p=0.08). Sinonasal, lung, cardio-vascular and kidney
      involvements were all accurately identified by PET, except in one MPA patient
      with glomerulonephritis. As expected, skin, joint, eye and peripheral nervous
      system impairments were not detected by PET. No occult site was detected by PET,
      except in 2 salivary gland FDG uptake without clinical abnormalities. Patients
      with GPA exhibited a higher number of positive sites on PET (2 [1.75-2.25] versus
      0.5 [0-1], p=0.006) than patients with MPA/EGPA. In pooled data including our
      study and the literature data of GPA patients (n=31), SUVmax was associated with
      Birmingham Vasculitis Activity Score (BVAS) (r=0.49; p=0.03). CONCLUSION: FDG
      PET/CT accurately identifies organ localizations in GPA, other than in nervous
      system, eye and skin, but do not bring additional benefit to the usual organ
      screening. The value of FDG-PET/CT in other ANCA-associated vasculitis need to be
      further addressed.

PMID- 24121047
TI  - Commentary on: Opioid and noradrenergic contributions of tapentadol in
      experimental neuropathic pain.

PMID- 24121048
TI  - Glucocorticoid receptor expression and sub-cellular localization in dopamine
      neurons of the rat midbrain.
AB  - Stress plays an important role in the development of addiction. Animals subjected
      to stress exhibit sensitized responses to psychostimulant drugs, and this
      sensitized response is associated with functional adaptations of the mesolimbic
      dopamine system. These adaptations likely arise from direct or indirect effects
      of glucocorticoids on dopaminergic neurons. Though glucocorticoid receptor
      expression in midbrain dopaminergic neurons has been examined in previous
      studies, results have been somewhat equivocal. We sought to clarify this issue by
      analyzing tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) co
      localization in the rat midbrain by dual fluorescence immunohistochemistry. We
      also examined sub-cellular localization of the GR in rat midbrain neurons after
      acute restraint stress. Adult Long-Evans rats were sacrificed 0, 30, 60 or 120min
      after 30min of restraint stress. A control group did not undergo restraint. Blood
      samples were collected immediately before and after restraint for measurement of
      plasma corticosterone by enzyme immunoassay. Glucocorticoid receptors were
      observed in dopaminergic neurons in both the substantia nigra (SN) and ventral
      tegmental area (VTA). The degree of co-localization of TH and GR did not differ
      between the VTA and the SN. All animals subjected to stress exhibited significant
      increases in plasma corticosterone. Significant translocation of GR signal to
      cell nuclei was observed after restraint in the SN, but not in the VTA. These
      results suggest that stress-induced glucocorticoid secretion could trigger
      functional changes in the mesolimbic dopamine system by direct activation of
      glucocorticoid receptors in dopaminergic neurons. 

PMID- 24121049
TI  - Improvements on colony morphology identification towards bacterial profiling.
AB  - Colony morphology may be an indicator of phenotypic variation, this being an
      important adaptive process adopted by bacteria to overcome environmental
      stressors. Furthermore, alterations in colony traits may reflect increased
      virulence and antimicrobial resistance. Despite the potential relevance of using
      colony morphological traits, the influence of experimental conditions on colony
      morphogenesis has been scarcely studied in detail. This study aims to clearly and
      systematically demonstrate the impact of some variables, such as colony growth
      time, plate colony density, culture medium, planktonic or biofilm mode of growth
      and strain genetic background, on bacterial colony morphology features using two
      Pseudomonas aeruginosa strains. Results, based on 5-replicate experiments,
      demonstrated that all variables influenced colony morphogenesis and 18 different
      morphotypes were identified, showing different sizes, forms, colours, textures
      and margins. Colony growth time and composition of the medium were the variables
      that caused the highest impact on colony differentiation both derived from
      planktonic and biofilm cultures. Colony morphology characterization before 45 h
      of incubation was considered inadequate and TSA, a non-selective medium, provided
      more colony diversity in contrast to P. aeruginosa selective media. In
      conclusion, data obtained emphasized the need to perform comparisons between
      colony morphologies in equivalent experimental conditions to avoid
      misinterpretation of microbial diagnostics and biomedical studies. Since colony
      morphotyping showed to be a reliable method to evaluate phenotypic switching and
      also to infer about bacterial diversity in biofilms, these unambiguous
      comparisons between morphotypes may offer a quite valuable input to clinical
      diagnosis, aiding the decision-making towards the selection of the most suitable
      antibiotic and supportive treatments.

PMID- 24121050
TI  - Stercoral perforation of the colon in sigmoid colostomy patients: Two case
      reports.
AB  - INTRODUCTION: Stercoral perforation of the colon has rarely been reported. Only 3
      cases of stercoral perforation of the colon proximal to an end colostomy have
      been reported. We present two cases of stercoral perforation of the colon in end
      colostomy patients. PRESENTATION OF CASE: A 70-year-old man who had undergone
      abdomino-perineal excision for anal cancer was referred for left lower quadrant
      pain and fever. Stercoral perforation was discovered along the distal descending
      colon, proximal to the end sigmoid colostomy. The patient underwent segmental
      resection of the colon and revision of the stoma and was discharged on
      postoperative day 32. A 71-year-old woman who had undergone abdomino-perineal
      excision for distal rectal cancer with preoperative chemoradiation presented
      fever with 2 days of low abdominal pain. The patient had sacral bone and lung
      metastases from rectal cancer and suffered from chronic constipation. Stercoral
      perforation was found around the sigmoid colon, just proximal to the end sigmoid
      colostomy. The patient underwent simple repair of the perforated colon through
      the parastomal incision. On postoperative day 8, leakage occurred at the repair
      site. Segmental resection of the colon and revision of the stoma were performed.
      She was discharged 44 days after the initial surgery. DISCUSSION: Segmental
      resection of the perforated colon, rather than simple repair, appears to improve
      postoperative outcomes. CONCLUSION: As the number of cancer survivors increases,
      appropriate management of constipation is important to prevent stercoral
      perforation during follow-up.

PMID- 24121051
TI  - Laparoscopic management of a strangulated internal hernia underneath the left
      external iliac artery.
AB  - INTRODUCTION: Internal herniation of a small bowel behind pelvic vessels is a
      rare complication seen after pelvic lymphadenectomy. PRESENTATION OF CASE: A 56
      year-old woman was operated due to a gynecological cancer. 4 years thereafter she
      presented with a 2 days history of abdominal pain and vomiting. Clinical and
      radiological findings indicated a small bowel obstruction. A loop of small bowel
      had herniated behind the left external iliac artery. Using laparoscopic technique
      the herniated bowel was reduced. Due to limited peritoneum around the area and
      skeletonized vessel, we decided not to do any repair of the hernia orifice. The
      postoperative recovery was uneventful, bowel activity returned to normal and she
      was discharged the next day. Follow-up was done at 1 month and the latest at 10
      months. She didn't experience pain or discomfort after the operation. DISCUSSION:
      Due to limited peritoneum around the skeletonized vessel, we decided to leave the
      hernia orifice unrepaired. We found it hazardous to do any direct suture of the
      orifice or use a free peritoneal graft to repair the defect as the fibrosis and
      inflammatory process might have compromised the artery or the vein. A longer
      follow-up of the patient is needed to clearly conclude if this simple procedure
      has been sufficient. We agreed that if the patient would experience any sign of
      recurrence and need another operation we would close the defect at that time.
      CONCLUSION: 4 years after pelvic lymphadenectomy a small bowel herniation behind
      an external iliac artery occurred. The patient was successfully treated with
      reduction of the small bowel using laparoscopic technique. A quick recovery with
      minimal discomfort and no sign of recurrence after 10 months made our approach an
      acceptable surgical option.

PMID- 24121052
TI  - Non-surgical pneumoperitoneum after oro-genital intercourse.
AB  - INTRODUCTION: In many cases, a pneumoperitoneum is due to air escaping from a
      perforated hollow viscus or surgical intervention but there are increasing
      reports of non-surgical causes. PRESENTATION OF CASE: We report a case where a
      pneumoperitoneum was identified after oro-genital sexual intercourse. DISCUSSION:
      There were nineteen reported cases of non-surgical pneumoperitoneum from
      gynaecologic causes up to May 2013. We report an additional case four hours after
      oro-genital intercourse. Close clinical observation and symptomatic treatment are
      usually all that is required but operative interventions should be considered if
      the patient develops abdominal pain, peritoneal signs, fever or leukocytosis
      during observation. CONCLUSION: This adds to the world literature on non-surgical
      pneumoperitoneum from oro-genital intercourse. Clinicians should be aware of this
      condition and focus on medical-sexual history as this information could prevent a
      patient from being exposed to expensive diagnostics and invasive operative
      treatments. Patients should also be educated about the mechanisms to avoid future
      possible diagnostic dilemmas.

PMID- 24121053
TI  - Comparative study on the hemocytes of subtropical oysters Saccostrea kegaki
      (Torigoe & Inaba, 1981), Ostrea circumpicta (Pilsbry, 1904), and Hyotissa hyotis
      (Linnaeus, 1758) in Jeju Island, Korea: morphology and functional aspects.
AB  - We first characterized the morphology and immune-related activities of hemocytes
      in the subtropical oysters Saccostrea kegaki, Ostrea circumpicta, and Hyotissa
      hyotis using light microscopy and flow cytometry. Hemocytes of these three oyster
      species were classified into three main types: 1) granulocytes containing
      numerous granules in the cytoplasm, 2) hyalinocytes with no or fewer granules,
      and 3) blast-like cells characterized by the smallest size and very thin
      cytoplasm. The percentage of each hemocyte population was similar in all species;
      hyalinocytes were the most abundant cell in the hemolymph accounting for more
      than 59%, followed by granulocytes (23-31%) and blast-like cells (3-5%). The size
      of granulocytes of S. kegaki was smaller (P < 0.05) than those of O. circumpicta
      and H. hyotis. Light microscopy also allowed the description of vacuolated cells
      characterized by large vacuoles in the cytoplasm. Flow cytometry analysis
      confirmed that the granulocytes of the three oyster species were the major
      hemocytes engaged in cellular defense with the largest lysosome content, and the
      most active phagocytosis activity and oxidative activity, as was previously
      reported in several marine bivalves. Phagocytic activity was the lowest in S.
      kegaki hemocytes, and PMA-stimulated oxidative activity was the lowest in H.
      hyotis hemocytes. Our results provide the basic information of hemocytes
      population of three subtropical oysters for further investigations associated
      with various environmental disease stresses.

PMID- 24121054
TI  - Toxicological and pharmacological concerns on oxidative stress and related
      diseases.
AB  - Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and
      hydroxyl radical are generated as the natural byproduct of normal oxygen
      metabolism, they can create oxidative damage via interaction with bio-molecules.
      The role of oxidative stress as a remarkable upstream part is frequently reported
      in the signaling cascade of inflammation as well as chemo attractant production.
      Even though hydrogen peroxide can control cell signaling and stimulate cell
      proliferation at low levels, in higher concentrations it can initiate apoptosis
      and in very high levels may create necrosis. So far, the role of ROS in cellular
      damage and death is well documented with implicating in a broad range of
      degenerative alterations e.g. carcinogenesis, aging and other oxidative stress
      related diseases (OSRDs). Reversely, it is cleared that antioxidants are
      potentially able to suppress (at least in part) the immune system and to enhance
      the normal cellular protective responses to tissue damage. In this review, we
      aimed to provide insights on diverse OSRDs, which are correlated with the concept
      of oxidative stress as well as its cellular effects that can be inhibited by
      antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin
      receptor blockers, statins, nebivolol and carvedilol, pentaerythritol
      tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone
      or combined) are the potential medicines that can be used to control OSRD. 

PMID- 24121055
TI  - Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to
      particles.
AB  - Exposure to particles has been suggested to generate hepatosteatosis by oxidative
      stress mechanisms. We investigated lipid accumulation in cultured human
      hepatocytes (HepG2) and rat liver after exposure to four different carbon-based
      particles. HepG2 cells were exposed to particles for 3h and subsequently
      incubated for another 18h to manifest lipid accumulation. In an animal model of
      metabolic syndrome we investigated the association between intake of carbon black
      (CB, 14nm) particles and hepatic lipid accumulation, inflammation and gene
      expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a
      concentration-dependent increase in intracellular lipid content after exposure to
      CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic
      acid. Similar results were observed in HepG2 cells after exposure to diesel
      exhaust particles, fullerenes C60 or pristine single-walled carbon nanotubes. All
      four types of particles also generated oxidatively damaged DNA, assessed as
      formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after
      3h exposure. The animal model of metabolic syndrome showed increased lipid load
      in the liver after one oral exposure to 6.4mg/kg of CB in lean Zucker rats. This
      was not associated with increased iNOS staining in the liver, indicating that the
      oral CB exposure was associated with hepatic steatosis rather than
      steatohepatitis. The lipid accumulation did not seem to be related to increased
      lipogenesis because there were unaltered gene expression levels in both the HepG2
      cells and rat livers. Collectively, exposure to particles is associated with
      oxidative stress and steatosis in hepatocytes. 

PMID- 24121056
TI  - Mechanism and biological relevance of blue-light (420-453 nm)-induced
      nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in
      human skin in vitro and in vivo.
AB  - Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and S
      nitrosothiols, which upon UVA radiation decompose under high-output NO formation
      and exert NO-specific biological responses such as increased local blood flow or
      reduced blood pressure. To avoid the injurious effects of UVA radiation, we here
      investigated the mechanism and biological relevance of blue-light (420-453 nm)
      induced nonenzymatic NO generation from photolabile nitric oxide derivates in
      human skin in vitro and in vivo. As quantified by chemiluminescence detection
      (CLD), at physiological pH blue light at 420 or 453 nm induced a significant NO
      formation from S-nitrosoalbumin and also from aqueous nitrite solutions by a to
      date not entirely identified Cu(1+)-dependent mechanism. As detected by electron
      paramagnetic resonance spectrometry in vitro with human skin specimens, blue
      light irradiation significantly increased the intradermal levels of free NO. As
      detected by CLD in vivo in healthy volunteers, irradiation of human skin with
      blue light induced a significant emanation of NO from the irradiated skin area as
      well as a significant translocation of NO from the skin surface into the
      underlying tissue. In parallel, blue light irradiation caused a rapid and
      significant rise in local cutaneous blood flow as detected noninvasively by using
      micro-light-guide spectrophotometry. Irradiation of human skin with moderate
      doses of blue light caused a significant increase in enzyme-independent cutaneous
      NO formation as well as NO-dependent local biological responses, i.e., increased
      blood flow. The effects were attributed to blue-light-induced release of NO from
      cutaneous photolabile NO derivates. Thus, in contrast to UVA, blue-light-induced
      NO generation might be therapeutically used in the treatment of systemic and
      local hemodynamic disorders that are based on impaired physiological NO
      production or bioavailability.

PMID- 24121057
TI  - Genetic ablation of 12/15-lipoxygenase but not 5-lipoxygenase protects against
      denervation-induced muscle atrophy.
AB  - Skeletal muscle atrophy is a debilitating outcome of a number of chronic diseases
      and conditions associated with loss of muscle innervation by motor neurons, such
      as aging and neurodegenerative diseases. We previously reported that denervation
      induced loss of muscle mass is associated with activation of cytosolic
      phospholipase A2 (cPLA2), the rate-limiting step for the release of arachidonic
      acid from membrane phospholipids, which then acts as a substrate for metabolic
      pathways that generate bioactive lipid mediators. In this study, we asked whether
      5- and 12/15-lipoxygenase (LO) lipid metabolic pathways downstream of cPLA2
      mediate denervation-induced muscle atrophy in mice. Both 5- and 12/15-LO were
      activated in response to surgical denervation; however, 12/15-LO activity was
      increased ~2.5-fold versus an ~1.5-fold increase in activity of 5-LO. Genetic and
      pharmacological inhibition of 12/15-LO (but not 5-LO) significantly protected
      against denervation-induced muscle atrophy, suggesting a selective role for the
      12/15-LO pathway in neurogenic muscle atrophy. The activation of the 12/15-LO
      pathway (but not 5-LO) during muscle atrophy increased NADPH oxidase activity,
      protein ubiquitination, and ubiquitin-proteasome-mediated proteolytic
      degradation. In conclusion, this study reveals a novel pathway for neurogenic
      muscle atrophy and suggests that 12/15-LO may be a potential therapeutic target
      in diseases associated with loss of innervation and muscle atrophy. 

PMID- 24121058
TI  - MEK in cancer and cancer therapy.
AB  - The mitogen-activated extracellular signal-regulated kinase (MEK) pathway is one
      of the best-characterized kinase cascades in cancer cell biology. It is triggered
      by either growth factors or activating mutations of major oncogenic proteins in
      this pathway, the most common being Ras and Raf. Deregulation of this pathway is
      frequently observed and plays a central role in the carcinogenesis and
      maintenance of several cancers, including melanoma, pancreatic, lung, colorectal,
      and breast cancers. Targeting these kinases offers promise of novel therapies.
      MEK inhibitors (MEKi) are currently under evaluation in clinical trials and many
      have shown activity. In this review, we comprehensively examine the role of the
      MEK pathway in carcinogenesis and its therapeutic potential in cancer patients,
      with a focus on MEKi. We describe the clinical perspectives of MEKi in the two
      main models of Ras-ERK driven tumors, BRAF-mutant ("addicted" to the pathway) and
      KRAS-mutant (non-"addicted"). We also highlight the known mechanisms of
      resistance to MEKi and emerging strategies to overcome it. 

PMID- 24121059
TI  - A next generation enzymatic magnesium assay on the Abbott ARCHITECT chemistry
      system meets performance goals based on biological variation.
AB  - OBJECTIVE: To evaluate the performance of the Abbott ARCHITECT enzymatic assay
      for magnesium (3P68) in serum/plasma and urine against analytical goals based on
      biological variation. METHODS: Analytical performance was evaluated according to
      CLSI protocols. Precision was examined using commercial chemistry controls.
      Accuracy was assessed against NIST SRM 956c, electrolytes in human serum.
      Correlation with the arsenazo Mg assay (7D70) was completed using patient samples
      (plasma, N = 101; urine, N = 90). Common interferences were examined in pooled
      patient specimens with high and low magnesium concentrations. RESULTS: The
      enzymatic Mg assay displayed imprecision of 1.7% at 0.72 mmol/L and 1.4% at 1.80
      mmol/L (20 days, one calibration, one reagent lot). The linear range was verified
      between 0.18-7.0 mmol/L (plasma) and 0.01-10.69 mmol/L (urine). Results of the
      enzymatic assay (x) correlated well with the predicate assay (y) with the
      relationships y = 0.891x + 0.035, R = 0.967 (plasma) and y = 1.181x + 0.086, R =
      0.997 (urine). Mean bias of the NIST SRM 956 c samples was -1.4%. This method
      showed minimal interference by hemoglobin (3g/L as hemolysate), lipemia (20 g/L
      Intralipid), unconjugated bilirubin (531 MUmol/L), and ascorbate (680 MUmol/L).
      CONCLUSIONS: The ARCHITECT Magnesium assay 3P68 achieved the desirable analytical
      quality specification of 4.8% for total allowable error. In comparison to the
      7D70 assay, notable improvements are seen in precision, 30-day calibration
      stability, and minimal interference by hemolyzed and lipemic samples.

PMID- 24121060
TI  - Electroconvulsive seizure induces thrombospondin-1 in the adult rat hippocampus.
AB  - Synaptic dysfunction has recently gained attention for its involvement in mood
      disorders. Electroconvulsive therapy (ECT) possibly plays a role in synaptic
      repair. However, the underlying mechanisms remain uncertain. Thrombospondin-1
      (TSP-1), a member of the TSP family, is reported to be secreted by astrocytes and
      to regulate synaptogenesis. We investigated the effects of electroconvulsive
      seizure (ECS) on the expression of TSPs in the adult rat hippocampus. Single and
      repeated ECS significantly increased TSP-1 mRNA expression after 2h and returned
      to sham levels at 24h. Conversely, the TSP-2 and -4 mRNA levels did not change.
      Only repeated ECS induced TSP-1 proteins. ECS also induced glial fibrillary
      acidic protein (GFAP) expression. The GFAP expression occurred later than the TSP
      1 mRNA expression following single ECS; however, it occurred earlier and was more
      persistent following repeated ECS. ECS had no effect on the alpha2delta-1 or
      neuroligin-1 expressions, both of which are TSP-1 receptors. Furthermore, chronic
      treatment with antidepressants did not induce the expression of TSP-1 or GFAP.
      These findings suggest that repeated ECS, but not chronic treatment with
      antidepressants, induces TSP-1 expression partially via the activation of
      astrocytes. Therefore, TSP-1 is possibly involved in the synaptogenic effects of
      ECS. 

PMID- 24121062
TI  - The brain through the retina: the flash electroretinogram as a tool to
      investigate psychiatric disorders.
AB  - Investigating the living brain remains one of the major obstacles in psychiatry
      research in order to better understand the biological underpinning of brain
      disorders. Novel approaches are needed to study brain functions indirectly. Since
      it is part of the central nervous system, retinal functions as measured with the
      flash electroretinogram (ERG) may reflect the central dysfunctions reported in
      psychiatric disorders. This review describes the flash ERG anomalies reported in
      patients with psychiatric disorders such as seasonal affective disorder,
      schizophrenia, autism spectrum disorder and drug addiction and discusses how
      changes in retinal functions might be used as biomarkers for psychiatric disorder
      as well as a potential aid to diagnosis in psychiatry. 

PMID- 24121061
TI  - Behavioral and neurochemical effects of repeated MDMA administration during late
      adolescence in the rat.
AB  - Adolescents and young adults disproportionately abuse 3,4
      methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA
      research has concentrated on adults, the effects of MDMA on the developing brain
      remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline)
      during late adolescence and assessed anxiety-like behavior and monoamine levels
      during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline
      with contextual cues over 4 twice-daily sessions. Five days after conditioning,
      anxiety-like behavior was examined with the open field test and brain tissue was
      collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5
      hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus
      by high-pressure liquid chromatography (HPLC). In a separate group of rats,
      anxiety-like and avoidant behaviors were measured using the light-dark box test
      under similar experimental conditions. MDMA conditioning caused a place aversion
      at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the
      open field and avoidant behavior in light-dark box test at the same dose.
      Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and
      5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we
      show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late
      adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by
      region-specific alterations in 5-HT levels during abstinence. These results
      suggest that MDMA causes a region-specific dysregulation of the serotonin system
      during adolescence that may contribute to maladaptive behavior. 

PMID- 24121063
TI  - BDNF signaling is necessary for the antidepressant-like effect of naringenin.
AB  - Previous studies in our laboratory have demonstrated that naringenin produced
      antidepressant-like action in tail suspension test (TST). However, the underlying
      mechanisms involved in neurotrophin system by which naringenin works have not
      been investigated. The present study extends earlier works on the role of brain
      derived neurotrophic factor (BDNF) in regulating the antidepressant-like actions
      of naringenin in chronic unpredictable mild stress (CUMS). We showed that a 21
      day regimen with naringenin reversed the decreased sucrose preference in sucrose
      preference test (SPT) and the prolonged first feeding latency in novelty
      suppressed feeding test (NSFT), without affecting home-cage feeding consumption.
      In addition, we also found that naringenin promoted BDNF expression in the
      hippocampus but not in the frontal cortex in both non-stressed and CUMS mice.
      Moreover, the antidepressant-like effect of naringenin in SPT and NSFT induced by
      naringenin administration were totally abolished by K252a, an inhibitor of BDNF
      receptor tropomyosin-related kinase receptor B (TrkB). In conclusion, our
      findings suggest that the antidepressant-like effect of naringenin may be
      mediated, at least in part, by the activation of BDNF signaling in the
      hippocampus. 

PMID- 24121064
TI  - Sertraline decreases serum level of interleukin-6 (IL-6) in hemodialysis patients
      with depression: results of a randomized double-blind, placebo-controlled
      clinical trial.
AB  - BACKGROUND: This study was designed to assess the effect of sertraline on serum
      concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      IL-10 and high-sensitivity C-reactive protein (hs-CRP) of depressed hemodialysis
      (HD) patients. METHODS: During a randomized, double-blind, placebo-controlled
      trial, fifty depressed HD patients were allocated to receive sertraline or
      placebo for 12 weeks. Patients' depression was assessed using Beck Depression
      Inventory-second edition (BDI-II). Biochemical parameters (hemoglobin, serum
      albumin, iron stores, etc.) and serum IL-6, IL-10, TNF-alpha, and hs-CRP levels
      were measured at baseline and at weeks 6 and 12 of the study. RESULTS: Sertraline
      significantly improved depression symptoms in 47.5% of the patients. Compared
      with placebo, serum levels of IL-6 significantly decreased (P<0.01) in the
      sertraline group at week 12 of the study. Although serum level of TNF-alpha
      decreased and serum level of IL-10 increased in sertraline group at week 12
      versus initiation of the study, no significant differences were found between
      sertraline and placebo groups. Serum hs-CRP did not display differences neither
      for inter- nor intra-group comparisons. Hemoglobin and serum albumin
      concentrations were significantly lower at week 12 in the placebo versus
      sertraline group (P=0.012 and P=0.006, respectively). No significant differences
      were observed in the inflammatory mediators between responders and non-responders
      to sertraline. CONCLUSIONS: Compared with placebo, sertraline significantly
      decreased serum level of IL-6. The anti-inflammatory effect of sertraline was
      independent to its efficacy for depression treatment. Sertraline could be a
      promising strategy to reduce the systemic inflammation and to treat depression in
      HD patients.

PMID- 24121065
TI  - Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid
      nanoparticle formulations.
AB  - Many cationic lipids have been developed for lipid-based nanoparticles (LNPs) for
      delivery of siRNA and microRNA (miRNA). However, less attention has been paid to
      "helper lipids". Here, we investigated several "helper lipids" and examined their
      effects on the physicochemical properties such as particle size and zeta
      potential, as well as cellular uptake and transfection efficiency. We found that
      inclusion of oleic acid (OA), an unsaturated fatty acid, into the LNP formulation
      significantly enhanced the delivery efficacy for siRNA and miRNA. For proof-of
      concept, miR-122, a liver-specific microRNA associated with many liver diseases,
      was used as a model agent to demonstrate the hepatic delivery efficacy both in
      tumor cells and in animals. Compared to Lipofectamine 2000, a commercial
      transfection agent, LNPs containing OA delivered microRNA-122 in a more efficient
      manner with a 1.8-fold increase in mature miR-122 expression and a 20% decrease
      in Bcl-w, a target of microRNA-122. In comparison with Invivofectamine, a
      commercial transfection agent specifically designed for hepatic delivery, LNPs
      containing OA showed comparable liver accumulation and in vivo delivery
      efficiency. These findings demonstrated the importance of "helper lipid"
      components of the LNP formulation on the cellular uptake and transfection
      activity of siRNA and miRNA. LNPs containing OA is a promising nanocarrier system
      for the delivery of RNA-based therapeutics in liver diseases. 

PMID- 24121066
TI  - Estrogen receptor-mediated transcription involves the activation of multiple
      kinase pathways in neuroblastoma cells.
AB  - While many physiological effects of estrogens (E) are due to regulation of gene
      transcription by liganded estrogen receptors (ERs), several effects are also
      mediated, at least in part, by rapid non-genomic actions of E. Though the
      relative importance of rapid versus genomic effects in the central nervous system
      is controversial, we showed previously that membrane-limited effects of E,
      initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could
      potentiate transcriptional effects of 17beta-estradiol from an estrogen response
      element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors
      and activators in a pharmacological approach, we show that activation of
      phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein
      kinase (MAPK) pathways, dependent on a Galphaq coupled receptor signaling are
      important in this transcriptional potentiation. We further demonstrate, using
      ERalpha phospho-deficient mutants, that E2-BSA mediated phosphorylation of
      ERalpha is one mechanism to potentiate transcription from an ERE reporter
      construct. This study provides a possible mechanism by which signaling from the
      membrane is coupled to transcription in the nucleus, providing an integrated view
      of hormone signaling in the brain. 

PMID- 24121067
TI  - Dexamethasone suppressibility and adrenal and ovarian venous effluents of 5alpha
      reduced C19 conjugates in hyperandrogenic women.
AB  - Several C19 conjugates, derived via 5alpha-reductase activity, are putative
      markers of peripheral androgen action and have been shown to correlate well with
      various clinical manifestations of androgen excess. While no ovarian vein
      gradient has been found for androsterone sulfate (ADT-S), androsterone
      glucuronide (ADT-G), 5alpha-androstane-3alpha,17beta-diol sulfate (3alpha-diol
      S), and 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-diol-G), the
      contribution of the adrenal gland to these conjugates has been unclear. Ten
      hirsute women were treated with 2mg/day dexamethasone (dex) for 7 days to
      determine the effect of adrenal androgen suppression on 5alpha-reduced androgen
      conjugate production. In addition, 11 women with mixed ovarian and adrenal
      androgen excess of non-neoplastic origin underwent ovarian and adrenal vein
      catheterization studies in order to assess gradients for the various C19
      steroids. These women had significantly higher levels of both unconjugated and
      conjugated androgens, except for ADT-S, compared to 8 matched normal ovulatory
      women. After dex treatment, total testosterone (TT), unbound T (UT),
      androstenedione (A) and DHEAS, all decreased by 31-75%. ADT-S, ADT-G, 3alpha-diol
      S and 3alpha-diol-G decreased by 48%, 71%, 46% and 68%, respectively. The
      suppression of the unconjugated androgens correlated highly and significantly
      with ADT-G. In the 11 patients undergoing adrenal venous catheterization, all
      patients exhibited a substantial adrenal gradient for TT and A. Of significance,
      in paired samples of peripheral venous and glandular effluents, no adrenal or
      ovarian gradient was found for any of the conjugated androgens. The data suggest
      that because dex suppression significantly decreases levels of the conjugated
      androgens, they are highly substrate dependent. However, since no adrenal or
      ovarian vein gradient exists, these markers of the manifestations of androgen
      excess largely reflect peripheral androgen metabolism. 

PMID- 24121068
TI  - Characterization of a novel model of chronic migraine.
AB  - Chronic migraine is a disabling condition that affects hundreds of millions of
      individuals worldwide. The development of novel migraine treatments has been
      slow, in part as a result of a lack of predicative animal models. We have
      developed a new model of chronic migraine involving the use of nitroglycerin
      (NTG), a known migraine trigger in humans. Chronic intermittent administration of
      NTG to mice resulted in acute mechanical hyperalgesia with each exposure as well
      as a progressive and sustained basal hyperalgesia. This chronic basal
      hyperalgesia occurred in a dose-dependent fashion and persisted for days after
      cessation of NTG administration. NTG-evoked hyperalgesia was exacerbated by the
      phosphodiesterase 5 inhibitor sildenafil, also a human migraine trigger,
      consistent with nitric oxide as a primary mediator of this hyperalgesia. The
      acute but not the chronic basal hyperalgesia was significantly reduced by the
      acute migraine therapy sumatriptan, whereas both the acute and chronic
      hyperalgesia was significantly attenuated by the migraine preventive therapy
      topiramate. Chronic NTG-induced hyperalgesia is a mouse model that may be useful
      for the study of mechanisms underlying progression of migraine from an episodic
      to a chronic disorder, and for the identification and characterization of novel
      acute and preventive migraine therapies. 

PMID- 24121069
TI  - [Prognosis for motor deficits after strokes in Burkina Faso].
AB  - Stroke is a common, severe, and disabling condition that is recognized as a major
      public health problem. Our goal was to study the clinical features and prognosis
      of motor deficits in stroke patients hospitalized in the neurology department of
      the Yalgado-Oeudraogo University Hospital in Burkina Faso. This cross-sectional
      study took place from March 1 through September 30, 2012. The study included all
      patients with motor disabilities following a CT-confirmed stroke that had
      occurred within the previous month. Patients were reviewed at one month (M1) and
      three months (M3) to assess their current treatment and their autonomy, by the
      Barthel Index. During the study period, 59 patients were hospitalized for stroke,
      56 with motor disabilities for a 95% prevalence of stroke with motor deficit.
      Their mean age was 57.8 +/- 17.7 years (range: 20 to 84 years), and the sex-ratio
      of 1.6 (male/female). Overall, 61% of the strokes were ischemic and 39%
      hemorrhagic, with an equal distribution of right and left hemiplegia (46.4% each)
      and 7% of the patients showing bilateral involvement. The mortality rate before
      M1 was 29% and before M3, 40%. On admission, 4% of patients had a Barthel Index
      greater than 60, at M1 35%, and at M3, 60%. Only 51% of patients received
      physical therapy. Characteristics significantly associated with functional
      recovery were age younger than 65 years (p = 0.0026), sphincter disorders at M1
      (p = 0.002), hemorrhagic stroke (compared to ischemic) (p = 0.0038), functional
      rehabilitation (p = 0.0012), and right (versus left) hemisphere damage (p =
      0.010).

PMID- 24121070
TI  - Holistic processing of impossible objects: evidence from Garner's speeded
      classification task.
AB  - Holistic processing, the decoding of the global structure of a stimulus while the
      local parts are not explicitly represented, is a basic characteristic of object
      perception. The current study was aimed to test whether such a representation
      could be created even for objects that violate fundamental principles of spatial
      organization, namely impossible objects. Previous studies argued that these
      objects cannot be represented holistically in long-term memory because they lack
      coherent 3D structure. Here, we utilized Garner's speeded classification task to
      test whether the perception of possible and impossible objects is mediated by
      similar holistic processing mechanisms. To this end, participants were asked to
      make speeded classifications of one object dimension while an irrelevant
      dimension was kept constant (baseline condition) or when this dimension varied
      (filtering condition). It is well accepted that ignoring the irrelevant dimension
      is impossible when holistic perception is mandatory, thus the extent of Garner
      interference in performance between the baseline and filtering conditions serves
      as an index of holistic processing. Critically, in Experiment 1, similar levels
      of Garner interference were found for possible and impossible objects implying
      holistic perception of both object types. Experiment 2 extended these results and
      demonstrated that even when depth information was explicitly processed,
      participants were still unable to process one dimension (width/depth) while
      ignoring the irrelevant dimension (depth/width, respectively). The results of
      Experiment 3 replicated the basic pattern found in Experiments 1 and 2 using a
      novel set of object exemplars. In Experiment 4, we used possible and impossible
      versions of the Penrose triangles in which information about impossibility is
      embedded in the internal elements of the objects which participant were
      explicitly asked to judge. As in Experiments 1-3, similar Garner interference was
      found for possible and impossible objects. Taken together, these findings
      emphasize the centrality of holistic processing style in object perception and
      suggest that it applies even for atypical stimuli such as impossible objects. 

PMID- 24121071
TI  - Comprehensive studies on the interaction of copper nanoparticles with bovine
      serum albumin using various spectroscopies.
AB  - Copper nanoparticles (NPs) of average size of ~7.5nm were synthesized by chemical
      reduction method. Fluorescence spectroscopy in synchronous and polarization modes
      were used to examine the nature of interaction between Cu NPs and bovine serum
      albumin (BSA) at different temperatures. Fluorescence quenching results suggest
      that Cu NPs interact with BSA molecule through static mechanism, as inferred from
      the quenching of BSA fluorophore. The calculated thermodynamic parameters (DeltaG
      degrees , DeltaH degrees , and DeltaS degrees ) hint that the binding process
      occurs spontaneously by involving hydrophobic forces. Synchronous fluorescence
      spectra reveal that the interaction of Cu NPs with BSA mostly changes the
      microenvironment of tryptophan and not of tyrosine residues. The formation of BSA
      Cu NPs ground state complex was also confirmed from the resonant light scattering
      and fluorescence polarization spectra. Circular dichroism and Raman spectra
      indicate that alpha-helicity of the BSA decreases due to the interaction with Cu
      NPs. It was also found that Cu NPs are located in the close proximity of BSA
      molecule, which transfer energy efficiently from the excited state of BSA
      fluorophore to the Cu NPs.

PMID- 24121072
TI  - Understanding interactions between immunoassay excipient proteins and surfactants
      at air-aqueous interface.
AB  - Air-aqueous interfacial properties of four excipient proteins commonly used in
      immunoassay reagent formulations were studied with shear rheology and surface
      characterization methods. A Du Nouy ring geometry was utilized to quantify the
      elastic (G') and viscous (G") shear moduli of protein interfacial networks and to
      probe the effect of several nonionic surfactants at various concentrations. Time
      sweep protocols of buffered protein solutions yielded G' in the range of 16 mN/m
      for bovine serum albumin (BSA), 6 mN/m for bovine gamma globulin (BGG), 7 mN/m
      for Mouse IgG, and 0.9 mN/m for sodium caseinate. G's were higher than G"s for a
      given protein. Effect of nonionic surfactants on G' of a protein was
      concentration dependent and the magnitude of protein displacement from the
      interface varied with Tween 20>Triton X-100>Triton X-405, with the exception of
      Mouse IgG. Degree of displacement of BSA from the interface by Tween 20 was
      approximately 66-fold greater than that of BGG whose displacement by Tween 20 was
      approximately 7-fold greater than that of Mouse IgG. Degree of displacement by
      Triton X-100 was comparable in case of studied proteins. Surface tension
      characterization suggests that the interfacial interactions between proteins and
      surfactants are driven not only by their surface activity but also by the network
      formation abilities of the proteins. Data presented here demonstrates a potential
      application of interfacial studies to sensitively identify discriminatory
      interactions between proteins and surfactants in immunoassay solutions.

PMID- 24121073
TI  - In situ preparation of magnetic Fe3O4 nanoparticles inside nanoporous poly(L
      glutamic acid)/chitosan microcapsules for drug delivery.
AB  - The magnetic polymer microcapsules, as a promising environmental stimuli
      responsive delivery vehicle, have been increasingly exploited to tackle the
      problem of remotely navigated delivery. This study presented a novel design and
      fabrication of magnetic poly(L-glutamic acid)/chitosan (PGA/CS) microcapsules.
      Magnetic Fe3O4 nanoparticles were in situ synthesized inside nanoporous PGA/CS
      microcapsules and resultant magnetic PGA/CS microcapsules were characterized.
      Mitoxantrone (MTX), an antineoplastic drug, was chosen as a water-soluble model
      drug to research the loading and release properties of the microcapsules. The
      results showed the carboxylate groups of PGA within polyelectrolyte walls could
      be used as binding sites for the absorption of iron ions and reaction sites for
      the synthesis of magnetic nanoparticles. Magnetic PGA/CS microcapsules were
      dissected using a dual-beam scanning electron microscope/focused ion beam
      (SEM/FIB) for morphological and microstructural examination. It was found that
      Fe3O4 nanoparticles with size of about 10nm were homogeneously dispersed in the
      polymer matrix and adhered to the pore walls of the microcapsules. Increasing the
      concentration of iron ions led to an increasing loading content of Fe3O4
      nanoparticles and an increase in the resultant magnetization. The magnetic PGA/CS
      microcapsules could be easily manipulated by an external magnetic field. The MTX
      loading capacity depended on loading time and MTX concentration. The high loading
      could be ascribed to spontaneous deposition of MTX induced by electrostatic
      interaction. The microcapsules exhibited sustained release behavior. The MTX
      release from microcapsules could be best described using Korsmeyer-Peppas and
      Baker-Lonsdale models, indicating the diffusion mechanism of drug release from
      both PGA/CS microcapsules and magnetic PGA/CS microcapsules. Therefore, the novel
      magnetic PGA/CS microcapsules are expected to find application in drug delivery
      systems because of the properties of magnetic sensitivity, high drug loading and
      sustained release.

PMID- 24121074
TI  - In vitro evaluation of TLR4 agonist activity: formulation effects.
AB  - Effective in vitro evaluation of vaccine adjuvants would allow higher throughput
      screening compared to in vivo studies. However, vaccine adjuvants comprise a wide
      range of structures and formulations ranging from soluble TLR agonists to complex
      lipid-based formulations. The effects of formulation parameters on in vitro
      bioactivity assays and the correlations with in vivo adjuvant activity is not
      well understood. In the present work, we employ the Limulus amebocyte lysate
      assay and a human macrophage cellular cytokine production assay to demonstrate
      the differences in in vitro bioactivity of four distinct formulations of the
      synthetic TLR4 agonist GLA: an aqueous nanosuspension (GLA-AF), an oil-in-water
      emulsion (GLA-SE), a liposome (GLA-LS), and an alum-adsorbed formulation (GLA
      Alum). Furthermore, we demonstrate the importance of the localization of GLA on
      in vitro potency. By comparing to previous published reports on the in vivo
      bioactivity of these GLA-containing formulations, we conclude that the most
      potent activators of the in vitro systems may not be the most potent in vivo
      adjuvant formulations. Furthermore, we discuss the formulation considerations
      which should be taken into account when interpreting data from in vitro adjuvant
      activity assays. 

PMID- 24121075
TI  - Combinatorial plasma polymerization approach to produce thin films for testing
      cell proliferation.
AB  - Plasma enhanced physical vapor depositions are extensively used to fabricate
      substrates for cell culture applications. One peculiarity of the plasma processes
      is the possibility to deposit thin films with reproducible chemical and physical
      properties. In the present work, a combinatorial plasma polymerization process
      was used to deposit thin carbon based films to promote cell adhesion, in the
      interest of testing cell proliferation as a function of the substrate chemical
      properties. Peculiarity of the combinatorial approach is the possibility to
      produce in just one deposition experiment, a set of surfaces of varying chemical
      moieties by changing the precursor composition. A full characterization of the
      chemical, physical and thermodynamic properties was performed for each set of the
      synthesized surfaces. X-ray photoelectron spectroscopy was used to measure the
      concentration of carboxyl, hydroxyl and amine functional groups on the substrate
      surfaces. A perfect linear trend between polar groups' density and precursors'
      concentration was found. Further analyses reveled that also contact angles and
      the correspondent surface energies of all deposited thin films are linearly
      dependent on the precursor concentration. To test the influence of the surface
      composition on the cell adhesion and proliferation, two cancer cell lines were
      utilized. The cell viability was assessed after 24 h and 48 h of cell culture.
      Experiments show that we are able to control the cell adhesion and proliferation
      by properly changing the thin film deposition conditions i.e. the concentration
      and the kind of chemical moiety on the substrate surface. The results also
      highlight that physical and chemical factors of biomaterial surface, including
      surface hydrophobicity and free energy, chemical composition, and topography, can
      altered cell attachment.

PMID- 24121076
TI  - Optimization of curcumin nanoemulsion for intranasal delivery using design of
      experiment and its toxicity assessment.
AB  - The objective of the study was to optimize curcumin nanoemulsion for intranasal
      delivery using design of experiment. Box-Behnken design was constructed using
      oil, surfactant and co-surfactant concentration as independent variables and
      their affect on response y1 (globule size) and y2 (zeta potential) were studied.
      The ANOVA test identified the significant factors that affected the responses.
      For globule size, percentage of oil, surfactant and co-surfactant were identified
      as significant model terms whereas for zeta potential, oil and co-surfactant were
      found to be significant. Critical factors affecting the responses were identified
      using perturbation and contour plots. The derived polynomial equation and contour
      graph aid in predicting the values of selected independent variables for
      preparation of optimum nanoemulsion with desired properties. Further, 2(4)
      factorial design was used to study influence of chitosan on particle size and
      zeta potential. The formulations were subjected to in vitro cytotoxicity using SK
      N-SH cell line and nasal ciliotoxicity studies. The developed formulations did
      not show any toxicity and were safe for intranasal delivery for brain targeting.
      In vitro diffusion studies revealed that nanoemulsions had a significantly higher
      release compared to drug solution. Ex vivo diffusion studies were carried out
      using sheep nasal mucosa fixed onto Franz diffusion cells. Mucoadhesive
      nanoemulsion showed higher flux and permeation across sheep nasal mucosa. 

PMID- 24121077
TI  - Solid-phase PEGylation of an immobilized protein cage on polyelectrolyte
      multilayer.
AB  - We used a quartz crystal microbalance (QCM) to quantitatively characterize solid
      phase poly(ethylene glycol) modification (PEGylation) of apoferritin that was
      electrostatically immobilized on the surface of a polyelectrolyte multilayer. The
      solid-phase PEGylation processes were monitored by analyzing QCM frequency
      shifts, which showed that the PEG chains were covalently introduced onto the
      surface of the immobilized apoferritin. We investigated the effect of PEG
      concentration, PEG molecular weight, and two-dimensional coverage of the
      immobilized apoferritin on the solid-phase PEGylation process in addition to the
      surface properties of the PEGylated apoferritin film, such as wettability and
      protein adsorption capacity. Since the reaction field is more spatially
      restricted in solid-phase PEGylation than in traditional aqueous-phase
      PEGylation, this study shows that a ferritin protein cage is potentially useful
      as a tailored building block, one that has well-defined structures different from
      the PEGylated ferritin prepared by an aqueous-phase approach. 

PMID- 24121078
TI  - Manufacture of layered collagen/chitosan-polycaprolactone scaffolds with
      biomimetic microarchitecture.
AB  - Chitosan-polycaprolactone (CH-PCL) copolymers with various PCL percentages less
      than 45 wt% were synthesized. Different CH-PCLs were respectively blended with
      Type-II collagen at prescribed ratios to fabricate a type of layered porous
      scaffolds with some biomimetic features while using sodium tripolyphosphate as a
      crosslinker. The compositions of different layers inside scaffolds were designed
      in a way so that from the top layer to the bottom layer collagen content changed
      in a degressive trend contrary to that of chitosan. A combinatorial processing
      technique involving adjustable temperature gradients, collimated photothermal
      heating and freeze-drying was used to construct desired microstructures of
      scaffolds. The resultant scaffolds had highly interconnected porous layers with a
      layer thickness of around 1mm and porous interface zones without visual clefts.
      Results obtained from SEM observations and measurements of pore parameters and
      swelling properties as well as mechanical examinations confirmed that graded
      average pore-size and porosity, gradient swelling index and oriented compressive
      modulus for certain scaffolds were synchronously achieved. In addition, certain
      evaluations of cell-scaffold constructs indicated that the achieved scaffolds
      were able to well support the growth of seeded chondrocytes. The optimized
      collagen/CH-PCL scaffolds are partially similar to articular cartilage
      extracellular matrix in composition, porous microarchitecture, water content and
      compressive mechanical properties, suggesting that they have promising potential
      for applications in articular cartilage repair.

PMID- 24121079
TI  - Structure of water at zwitterionic copolymer film-liquid water interfaces as
      examined by the sum frequency generation method.
AB  - A copolymer film composed of zwitterionic carboxymethylbetaine (CMB) and n-butyl
      methacrylate (BMA), Poly(CMB-r-BMA), was cast on a flat plane of an
      octadecyltrichlorosilane (ODS)-modified fused quartz prism with a semi
      cylindrical shape. CH stretching of the polymer film and O-H stretching of water
      at the surface of the film were examined using the sum frequency generation (SFG)
      technique. The C-H stretching band of the cast film, indicating a gauche defect
      of the film, was affected by the contact medium including dry nitrogen, water
      vapor-saturated nitrogen and liquid water. In contrast, the C-H stretching of an
      octadecyl group introduced onto the quartz prism for stable attachment of the
      cast film was not significantly changed by the contact medium. The O-H stretching
      band indicated that water molecules at the surface of the Poly(CMB-r-BMA) film in
      contact with liquid water were not greatly oriented in comparison with those at
      the surfaces of a bare prism, an ODS SAM-modified prism, and a prism covered with
      a PolyBMA film or a copolymer film of BMA and methacrylic acid or 2
      (dimethylamino)ethyl methacrylate. A similar small perturbation of the structure
      of water was previously observed in the vicinity of water-soluble zwitterionic
      polymers and zwitterionic copolymer films using Raman and attenuated total
      reflection infrared spectroscopies, respectively. A distinct effect of charge
      neutralization to diminish the perturbation of the structure of interfacial water
      around polymer materials was suggested.

PMID- 24121080
TI  - Galactose functionalized injectable thermoresponsive microgels for sustained
      protein release.
AB  - Novel galactose functionalized thermoresponsive injectable microgels, poly(N
      isopropylacrylamide-co-6-O-vinyladipoyl-D-galactose) P(NIPAAm-co-VAGA), have been
      fabricated using a combination of enzymatic transesterification and emulsion
      copolymerization. The microgels exhibit reversible temperature-responsive
      behavior, which can be tuned by varying the monomer feed ratio. The lower
      critical solution temperatures (LCSTs) of the materials are close to body
      temperature and can result in a rapid thermal gelation at 37  degrees C. Field
      emission scanning electron microscopy showed the resultant microgels to have
      porous structures, and dynamic light scattering experiments indicated a dramatic
      reduction in particle size as solutions of the polymers are heated through the
      LCST. The polymers can be loaded with protein (bovine serum albumin; BSA), and in
      vitro studies showed that the BSA release kinetics depend upon the temperature
      and copolymer composition. Microgels based on P(NIPAAm-co-VAGA) could hence serve
      as candidates for site-specific sustained release drug delivery systems.

PMID- 24121081
TI  - PBN derived amphiphilic spin-traps. II/Study of their antioxidant properties in
      biomimetic membranes.
AB  - The work reported herein deals with the evaluation of the antioxidant properties
      of bitailed amphiphilic alpha-phenyl-N-tert-butylnitrone derivatives (BPBNs)
      towards oxidation of an unsaturated lipid, the 1,2-dilinoleoyl-sn-glycero-3
      phosphocholine (DLoPC). Oxidation was induced either by UV light irradiation or
      radical initiators, i.e. the water soluble AAPH and the Fenton reaction, and the
      antioxidant evaluation was carried out using two biomimetic systems, namely
      Langmuir monolayers and large unilamellar vesicles. Measurement of the molecular
      area and the membrane fluidity of pure nitrone monolayers before and after UV
      irradiation demonstrated the better stability and antioxidant properties of
      B17PBN, the derivative with two C17H35 alkyl chains, compared to its analogue
      B11PBN with two C11H23 alkyl chains. At only 5% molar ratio of nitrone in mixed
      DLoPC/nitrone monolayers, a complete inhibition of the molecular area decrease
      was observed for B17PBN whereas B11PBN showed lower protection. The oxidation of
      mixed DLoPC/nitrones large unilamellar vesicles in the presence of free radicals
      arising from AAPH decomposition or Fenton reaction was assessed by measuring
      lipid conjugated dienes and thiobarbituric acid reactive substances on the whole
      series of nitrone, i.e. C11-, C13-, C15- and C17-based compounds. Compared to the
      saturated 1,2-dimyristoyl-sn-glycero-3-phosphocholine, all bitailed amphiphilic
      nitrones were able to decrease conjugated dienes and TBARS in both oxidative
      paradigms, demonstrating therefore antioxidant property. The inhibition of
      phospholipids oxidation was increased when increasing the concentration of
      nitrone with the two B11PBN and B13PBN derivatives exhibiting higher potency.
      This study underlines the importance in the choice of a model membrane system
      when evaluating the potency of antioxidants against lipid oxidation.

PMID- 24121082
TI  - Is there a potential relationship between prior hamstring strain injury and
      increased risk for future anterior cruciate ligament injury?
AB  - Hamstring strain injuries (HSIs) are the most prevalent injury in a number of
      sports, and while anterior cruciate ligament (ACL) injuries are less common, they
      are far more severe and have long-term implications, such as an increased risk of
      developing osteoarthritis later in life. Given the high incidence and severity of
      these injuries, they are key targets of injury preventive programs in elite
      sport. Evidence has shown that a previous severe knee injury (including ACL
      injury) increases the risk of HSI; however, whether the functional deficits that
      occur after HSI result in an increased risk of ACL injury has yet to be
      considered. In this clinical commentary, we present evidence that suggests that
      the link between previous HSI and increased risk of ACL injury requires further
      investigation by drawing parallels between deficits in hamstring function after
      HSI and in women athletes, who are more prone to ACL injury than men athletes.
      Comparisons between the neuromuscular function of the male and female hamstring
      has shown that women display lower hamstring-to-quadriceps strength ratios during
      isokinetic knee flexion and extension, increased activation of the quadriceps
      compared with the hamstrings during a stop-jump landing task, a greater time
      required to reach maximal isokinetic hamstring torque, and lower integrated
      myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat
      similarly, in athletes with a history of HSI, the previously injured limb,
      compared with the uninjured limb, displays lower eccentric knee flexor strength,
      a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical
      activity during maximal knee flexor eccentric contraction, a lower knee flexor
      eccentric rate of torque development, and lower voluntary myoelectrical activity
      during the initial portion of eccentric contraction. Given that the medial and
      lateral hamstrings have different actions at the knee joint in the coronal plane,
      which hamstring head is previously injured might also be expected to influence
      the likelihood of future ACL. Whether the deficits in function after HSI, as seen
      in laboratory-based studies, translate to deficits in hamstring function during
      typical injurious tasks for ACL injury has yet to be determined but should be a
      consideration for future work. 

PMID- 24121083
TI  - Ultrasound-guided versus fluoroscopy-guided sacroiliac joint intra-articular
      injections in the noninflammatory sacroiliac joint dysfunction: a prospective,
      randomized, single-blinded study.
AB  - OBJECTIVE: To compare the short-term effects and safety of ultrasound (US)-guided
      sacroiliac joint (SIJ) injections with fluoroscopy (FL)-guided SIJ injections in
      patients with noninflammatory SIJ dysfunction. DESIGN: Prospective, randomized
      controlled trial. SETTING: University hospital. PARTICIPANTS: Patients (N=120)
      with noninflammatory sacroiliac arthritis were enrolled. INTERVENTION: All
      procedures were performed using an FL or US apparatus. Subjects were randomly
      assigned to either the FL or US group. Immediately after the SIJ injections,
      fluoroscopy was applied to verify the correct placement of the injected
      medication and intravascular injections. MAIN OUTCOME MEASURES: Treatment effects
      and functional improvement were compared at 2 and 12 weeks after the procedures.
      RESULTS: The verbal numeric pain scale and Oswestry Disability Index improved at
      2 and 12 weeks after the injections without statistical significances between
      groups. Of 55 US-guided injections, 48 (87.3%) were successful and 7 (12.7%) were
      missed. The FL-guided SIJ approach exhibited a greater accuracy (98.2%) than the
      US-guided approach. Vascularization around the SIJ was seen in 34 of 55 patients.
      Among the 34 patients, 7 had vascularization inside the joint, 23 had
      vascularization around the joint, and 4 had vascularization both inside and
      around the joint. Three cases of intravascular injections occurred in the FL
      group. CONCLUSIONS: The US-guided approach may facilitate the identification and
      avoidance of the critical vessels around or within the SIJ. Function and pain
      relief significantly improved in both groups without significant differences
      between groups. The US-guided approach was shown to be as effective as the FL
      guided approach in treatment effects. However, diagnostic application in the SIJ
      may be limited because of the significantly lower accuracy rate (87.3%).

PMID- 24121084
TI  - Cardiac rehabilitation and outcome in stable outpatients with recent myocardial
      infarction.
AB  - OBJECTIVE: To compare the mortality rate and the rate of subsequent ischemic
      events (myocardial infarction [MI], ischemic stroke, or limb amputation) in
      patients with recent MI according to the use of cardiac rehabilitation or no
      rehabilitation. DESIGN: Longitudinal observational study. SETTING: Ongoing
      registry of outpatients. PARTICIPANTS: Patients (N=1043) with recent acute MI
      were recruited; of these, 521 (50%) participated in cardiac rehabilitation.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subsequent ischemic events
      and mortality rates were registered. RESULTS: Over a mean follow-up of 18 months,
      50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events
      (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate
      (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence
      interval [CI], 0.0-0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54
      events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2-0.7) were significantly
      lower in cardiac rehabilitation participants than in nonparticipants.
      Multivariate analysis confirmed that patients in cardiac rehabilitation had a
      significantly lower risk of death (hazard ratio=.08; 95% CI, .01-.63; P=.016) and
      a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95%
      CI, .30-1.42). CONCLUSIONS: The use of cardiac rehabilitation in patients with
      recent MI was independently associated with a significant decrease in the
      mortality rate and a nonsignificant decrease in the rate of subsequent ischemic
      events.

PMID- 24121085
TI  - T cells from autoimmune patients display reduced sensitivity to immunoregulation
      by mesenchymal stem cells: role of IL-2.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitor cells which have been
      shown to possess broad immunoregulatory and anti-inflammatory capabilities,
      making them a promising tool to treat autoimmune diseases (AIDs). Nevertheless,
      as in recent years T cells from AID patients have been found to resist
      suppression by regulatory T cells, the question of whether they could be
      regulated by MSCs arises. To use MSCs as a therapeutic tool in human autoimmune
      diseases, one prerequisite is that T cells from autoimmune patients will be
      sensitive to these stem cells. The aim of this work was to investigate the
      ability of healthy donor derived MSCs to inhibit the proliferation of T cells
      from two pathophysiologically different AIDs: Multiple Sclerosis (MS) and
      Myasthenia Gravis (MG). We show that MSC-induced inhibition of interferon-gamma
      production and surface expression of the CD3, CD4 and CD28 receptors by activated
      lymphocytes was similar in the AID patients and healthy controls. Contrarily, the
      MSCs' ability to suppress the proliferation of T cells of both diseases was
      significantly weaker compared to their ability to affect T cells of healthy
      individuals. Although we found that the inhibitory mechanism is mediated through
      CD14+ monocytes, the faulty cellular component is the patients' T cells. MSC
      treated MS and MG lymphocytes were shown to produce significantly more IL-2 than
      healthy subjects while coupling of the MSC treatment with neutralizing IL-2
      antibodies resulted in inhibition levels similar to those of the healthy
      controls. MSCs were also found to down-regulate the lymphocyte surface expression
      of the IL-2 receptor (CD25) through both transcription inhibition and induction
      of receptor shedding. Addition of IL-2 to MSC-inhibited lymphocytes restored
      proliferation thus suggesting a key role played by this cytokine in the
      inhibitory mechanism. Taken together, these results demonstrate the potential of
      a MSC-based cellular therapy for MS, MG and possibly other autoimmune diseases
      but also highlight the need for a better understanding of the underlying
      mechanisms for development and optimization of clinical protocols. 

PMID- 24121086
TI  - Lateralized alpha-band cortical networks regulate volitional modulation of beta
      band sensorimotor oscillations.
AB  - Sensorimotor rhythms (SMRs) are oscillatory brain activities in the alpha- and
      beta-bands across the sensorimotor regions of the brain. Each frequency band has
      its own specific function. The alpha-band oscillations are closely related to
      intrinsic cortical networks, whereas oscillations in the beta-band are relevant
      for the information transfer between the cortex and periphery, as well as for
      visual and proprioceptive feedback. This study aimed to investigate the
      interaction between these two frequency bands, under the premise that the
      regional modulation of beta-band power is linked to a cortical network in the
      alpha-band. We therefore designed a procedure to maximize the modulation of beta
      band activity over the sensorimotor cortex by combining kinesthetic motor-imagery
      with closed-loop haptic feedback. The cortical network activity during this
      procedure was estimated via the phase slope index in electroencephalographic
      recordings. Analysis of effective connectivity within the alpha-band network
      revealed an information flow between the precentral (premotor and primary motor),
      postcentral (primary somatosensory) and parietal cortical areas. The range of
      beta-modulation was connected to a reduction of an ipsilateral sensorimotor and
      parietal alpha-network and, consequently, to a lateralization of this network to
      the contralateral side. These results showed that regional sensorimotor
      oscillatory activity in the beta-band was regulated by cortical coupling of
      distant areas in the alpha-band. 

PMID- 24121087
TI  - Mapping hemispheric symmetries, relative asymmetries, and absolute asymmetries
      underlying the auditory laterality effect.
AB  - Functional hemispheric differences for speech and language processing have been
      traditionally studied by using verbal dichotic-listening paradigms. The commonly
      observed right-ear preference for the report of dichotically presented syllables
      is taken to reflect the left hemispheric dominance for speech processing.
      However, the results of recent functional imaging studies also show that both
      hemispheres - not only the left - are engaged by dichotic listening, suggesting a
      more complex relationship between behavioral laterality and functional
      hemispheric activation asymmetries. In order to more closely examine the
      hemispheric differences underlying dichotic-listening performance, we report an
      analysis of functional magnetic resonance imaging (fMRI) data of 104 right-handed
      subjects, for the first time combining an interhemispheric difference and
      conjunction analysis. This approach allowed for a distinction of homotopic brain
      regions which showed symmetrical (i.e., brain region significantly activated in
      both hemispheres and no activation difference between the hemispheres), relative
      asymmetrical (i.e., activated in both hemispheres but significantly stronger in
      one than the other hemisphere), and absolute asymmetrical activation patterns
      (i.e., activated only in one hemisphere and this activation is significantly
      stronger than in the other hemisphere). Symmetrical activation was found in large
      clusters encompassing temporal, parietal, inferior frontal, and medial superior
      frontal regions. Relative and absolute left-ward asymmetries were found in the
      posterior superior temporal gyrus, located adjacent to symmetrically activated
      areas, and creating a lateral-medial gradient from symmetrical towards absolute
      asymmetrical activation within the peri-Sylvian region. Absolute leftward
      asymmetry was also found in the post-central and medial superior frontal gyri,
      while rightward asymmetries were found in middle temporal and middle frontal
      gyri. We conclude that dichotic listening engages a bihemispheric cortical
      network, showing a symmetrical and mostly leftward asymmetrical pattern. The here
      obtained functional (a)symmetry map might serve as a basis for future studies
      which - by studying the relevance of the here identified regions - clarify the
      relationship between behavioral laterality measures and hemispheric asymmetry. 

PMID- 24121088
TI  - Identifying neuropathic pain using (18)F-FDG micro-PET: a multivariate pattern
      analysis.
AB  - Pain is a multidimensional experience emerging from the flow of information
      between multiple brain regions. A growing body of evidence suggests that
      pathological pain causes plastic changes of various brain regions. Here, we
      hypothesized that the induction of neuropathic pain alters distributed patterns
      of the resting-state brain activity in animal models, and capturing the altered
      pattern would enable identification of neuropathic pain at the individual level.
      We acquired micro-positron emission tomography with [(18)F]fluorodeoxyglucose
      (FDG micro-PET) images in awake rats with spinal nerve ligation (SNL) and without
      (sham) (SNL group, n=13; sham group, n=10). Multivariate pattern analysis (MVPA)
      with linear support vector machine (SVM) successfully identified the brain with
      SNL (92.31% sensitivity, 90.00% specificity, and 91.30% total accuracy).
      Predictive brain regions with increased metabolism were mainly located in
      prefrontal-limbic-brainstem areas including the anterior olfactory nucleus (AON),
      insular cortex (IC), piriform cortex (PC), septal area (SA), basal
      forebrain/preoptic area (BF/POA), amygdala (AMY), hypothalamus (HT), rostral
      ventromedial medulla (RVM) and the ventral midbrain (VMB). In contrast,
      predictive regions with decreased metabolism were observed in widespread cortical
      areas including secondary somatosensory cortex (S2), occipital cortex (OC),
      temporal cortex (TC), retrosplenial cortex (RSC), and the cerebellum (CBL). We
      also applied the univariate approach and obtained reduced prediction performance
      compared to MVPA. Our results suggest that developing neuroimaging-based
      diagnostic tools for pathological pain can be achieved by considering patterns of
      the resting-state brain activity. 

PMID- 24121089
TI  - Application of fused lasso logistic regression to the study of corpus callosum
      thickness in early Alzheimer's disease.
AB  - We propose a fused lasso logistic regression to analyze callosal thickness
      profiles. The fused lasso regression imposes penalties on both the l1-norm of the
      model coefficients and their successive differences, and finds only a small
      number of non-zero coefficients which are locally constant. An iterative method
      of solving logistic regression with fused lasso regularization is proposed to
      make this a practical procedure. In this study we analyzed callosal thickness
      profiles sampled at 100 equal intervals between the rostrum and the splenium. The
      method was applied to corpora callosa of elderly normal controls (NCs) and
      patients with very mild or mild Alzheimer's disease (AD) from the Open Access
      Series of Imaging Studies (OASIS) database. We found specific locations in the
      genu and splenium of AD patients that are proportionally thinner than those of
      NCs. Callosal thickness in these regions combined with the Mini Mental State
      Examination scores differentiated AD from NC with 84% accuracy. 

PMID- 24121090
TI  - Resuscitation in general practice--time for action: editorial on: "The presence
      of resuscitation equipment and influencing factors at General Practitioners'
      offices in Denmark: a cross-sectional study" by Niegsch ML, Krarup NT, Clausen
      NE.

PMID- 24121091
TI  - Quantifying oscillatory ventilation during exercise in patients with heart
      failure.
AB  - BACKGROUND: This study examined the validity of a novel software application to
      quantify measures of periodic breathing rest (PB) and oscillatory ventilation
      during exercise (EOV) in heart failure patients (HF). METHODS: Eleven male HF
      patients (age=53+/-8yrs, ejection fraction=17+/-4, New York Heart Association
      Class=III(7)/IV(4)) were recruited. Ventilation and gas exchange were collected
      breath-by-breath. Amplitude and period of oscillations in ventilation (VE), tidal
      volume (VT), end-tidal carbon dioxide [Formula: see text] , and oxygen
      consumption [Formula: see text] were measured manually (MAN) and using novel
      software which included a peak detection algorithm (PK), sine wave fitting
      algorithm (SINE), and Fourier analysis (FOUR). RESULTS: During PB, there were no
      differences between MAN and PK for amplitude of VE, VT, [Formula: see text] , or
      [Formula: see text] . Similarly, there were no differences between MAN and SINE
      for amplitude of VE or VT although [Formula: see text] and [Formula: see text]
      were lower with SINE (p<0.05). In contrast, the PK demonstrated significantly
      shorter periods for VE, VT, [Formula: see text] , and [Formula: see text]
      compared to MAN (p<0.05) whereas there were no differences in periods of
      oscillations between MAN and SINE or FOUR for all variables. During EOV, there
      were no differences between MAN and PK for amplitude of VE, VT, [Formula: see
      text] , and [Formula: see text] . SINE demonstrated significantly lower
      amplitudes for VT, [Formula: see text] , and [Formula: see text] (p<0.05)
      although VE was not different. PK demonstrated shorter periods for all variables
      (p<0.05) whereas there were no differences between MAN and SINE or FOUR for all
      variables. CONCLUSION: These data suggest PK consistently captures amplitudes
      while underestimating period. In contrast, SINE and FOUR consistently capture
      period although SINE underestimates amplitude. Thus, an optimal algorithm for the
      quantification of PB and/or EOV in patients with HF might combine multiple
      analysis methods.

PMID- 24121092
TI  - Exercise-induced oxygen desaturation in COPD patients without resting hypoxemia.
AB  - Exercise-induced oxygen desaturation (EID) is associated with increased risk of
      mortality in chronic obstructive pulmonary disease (COPD). Several screening
      tests have been proposed to predict EID, including FEV1, DLCO and baseline-SpO2.
      We aimed to validate a proposed cut-off of baseline-SpO2 <=95% as simple
      screening procedure to predict EID during six-minute walk test (6MWT). In
      addition, we studied the prevalence and characteristics of patients exhibited EID
      to SpO2nadir <=88%. 402 non-hypoxemic COPD patients performed 6MWT. Sensitivity
      and specificity of baseline SpO2 <=95% as a cut-off to predict EID and
      determinants of EID were investigated. 158 patients (39%) exhibited EID. The
      sensitivity of baseline-SpO2 <=95% to predict EID was 81.0%, specificity 49.2%,
      positive and negative predictive values were 50.8% and 80.0%, respectively. In a
      multivariate model, DLCO <50%, FEV1 <45%, PaO2 <10kPa, baseline-SpO2 <95%, and
      female sex were the strongest determinants of EID. Baseline oxygen saturation
      solely is inaccurate to predict EID. A combination of clinical characteristics
      (DLCO, FEV1, PaO2, baseline-SpO2, sex) increases the odds for EID in COPD. 

PMID- 24121093
TI  - Amino acid substitutions of Na,K-ATPase conferring decreased sensitivity to
      cardenolides in insects compared to mammals.
AB  - Mutagenesis analyses and a recent crystal structure of the mammalian Na,K-ATPase
      have identified amino acids which are responsible for high affinity binding of
      cardenolides (such as ouabain) which at higher doses block the enzyme in the
      phosphorylated state. Genetic analysis of the Na,K-ATPase of insects adapted to
      cardenolides in their food plants revealed that some species possess
      substitutions which confer strongly increased resistance to ouabain in the
      mammalian enzyme such as the substitution T797A or combined substitutions at
      positions 111 and 122. To test for the effect of these mutations against the
      background of insect Na,K-ATPase, we here expressed the ouabain sensitive Na,K
      ATPase alpha-subunit of Drosophila melanogaster together with the beta-subunit
      Nrv3 in baculovirus-infected Sf9 cells and introduced the substitutions N122H,
      T797A, Q111T-N122H, Q111V-N122H, all of which have been observed in cardenolide
      adapted insects. While all constructs showed similar expression levels, ouabain
      affinity of mutated Na,K-ATPases was reduced compared to the wild-type fly
      enzyme. Ouabain sensitivity of the ATPase activity in inhibition assays was
      significantly decreased by all mutations, yet whereas the IC50 for the single
      mutations of N122H (61.0 MUM) or T797A (63.3 MUM) was increased roughly 250-fold
      relative to the wild-type (0.24 MUM), the double mutations of Q111V-N122H (IC50
      550 MUM) and Q111T-N122H (IC50 583 MUM) proved to be still more effective
      yielding a 2.250-fold increased resistance to ouabain. The double mutations
      identified in cardenolide-adapted insects are more effective in reducing ouabain
      sensitivity of the enzyme than those found naturally in the rat Na,K-ATPase
      (Q111R-N122D) or in mutagenesis screens of the mammalian enzyme. Obviously, the
      intense selection pressure on cardenolide exposed insects has resulted in very
      efficient substitutions that decrease cardenolide sensitivity extremely.

PMID- 24121094
TI  - Tebufenozide disrupts ovarian development and function in silkmoths.
AB  - Adult development and production of up to 400 eggs within the pupal case of
      female silkmoths are both dependent on 20-hydroxyecdysone (20E), the steroid
      hormone of insects. When adult development was initiated with tebufenozide, the
      non-steroidal ecdysteroid agonist, instead of 20E, full development of all
      epidermal tissues like the wing was witnessed, but ovarian growth and egg
      formation was minimal. Administration of tebufenozide to female pharate adults
      caused disruption of the follicular epithelium, produced nurse cell damage, and
      inhibited oogenesis. Reduced ability to synthesize RNA and protein accompanied
      these tebufenozide induced morphological disturbances of the follicles. In vivo
      accumulation of vitellogenin (Vg) from the hemolymph was reduced in tebufenozide
      treated female ovaries as well as their ability to accumulate Vg in vitro.
      Determination of protein staining intensity and antibody reactivity of Vg pointed
      out that hemolymph Vg level remained fairly constant all through adult
      development whether induced by 20E or tebufenozide. Measurement of hemolymph
      volumes and hemolymph Vg levels of control and experimental animals allowed us to
      conclude that egg development involves the uptake of all the hemolymph proteins
      and not Vg alone. The loss of hemolymph that accompanies egg maturation was
      considerably reduced in tebufenozide initiated female pharate adults. 20E could
      not overcome ovarian growth inhibitory effects of tebufenozide. Dual mechanisms,
      one involving ecdysteroid antagonist action at the beginning of development, and
      the other unrelated to that function during heightened egg formation, are needed
      explain the biphasic inhibitory actions of tebufenozide on silkmoth ovaries. 

PMID- 24121095
TI  - Focus.

PMID- 24121097
TI  - Motivational support provided via email improves the effectiveness of internet
      delivered self-help treatment for insomnia: a randomized trial.
AB  - Internet-delivered treatment is effective for insomnia, but little is known about
      the beneficial effects of support. The aim of the current study was to
      investigate the additional effects of low-intensity support to an internet
      delivered treatment for insomnia. Two hundred and sixty-two participants were
      randomized to an internet-delivered intervention for insomnia with (n = 129) or
      without support (n = 133). All participants received an internet-delivered
      cognitive behavioral treatment for insomnia. In addition, the participants in the
      support condition received weekly emails. Assessments were at baseline, post
      treatment, and 6-month follow-up. Both groups effectively ameliorated insomnia
      complaints. Adding support led to significantly higher effects on most sleep
      measures (d = 0.3-0.5; p < 0.05), self-reported insomnia severity (d = 0.4; p <
      0.001), anxiety, and depressive symptoms (d = 0.4; p < 0.01). At the 6-month
      follow-up, these effects remained significant for sleep efficiency, sleep onset
      latency, insomnia symptoms, and depressive symptoms (d = 0.3-0.5; p < 0.05).
      Providing support significantly enhances the benefits of internet-delivered
      treatment for insomnia on several variables. It appears that motivational
      feedback increases the effect of the intervention and encourages more
      participants to complete the intervention, which in turn improves its
      effectiveness. 

PMID- 24121096
TI  - Psychological treatment of hypnotic-dependent insomnia in a primarily older adult
      sample.
AB  - OBJECTIVE: This study tested cognitive behavior therapy (CBT) in hypnotic
      dependent, late middle-age and older adults with insomnia. METHOD: Seventy
      volunteers age 50 and older were randomized to CBT plus drug withdrawal, placebo
      biofeedback (PL) plus drug withdrawal, or drug withdrawal (MED) only. The CBT and
      PL groups received eight, 45 min weekly treatment sessions. The drug withdrawal
      protocol comprised slow tapering monitored with about six biweekly, 30 min
      sessions. Assessment including polysomnography (PSG), sleep diaries, hypnotic
      consumption, daytime functioning questionnaires, and drug screens collected at
      baseline, posttreatment, and 1-year follow-up. RESULTS: Only the CBT group showed
      significant sleep diary improvement, sleep onset latency significantly decreased
      at posttreatment. For all sleep diary measures for all groups, including MED,
      sleep trended to improvement from baseline to follow-up. Most PSG sleep variables
      did not significantly change. There were no significant between group differences
      in medication reduction. Compared to baseline, the three groups decreased
      hypnotic use at posttreatment, down 84%, and follow-up, down 66%. There was no
      evidence of withdrawal side-effects. Daytime functioning, including anxiety and
      depression, improved by posttreatment. Rigorous methodological features,
      including documentation of strong treatment implementation and the presence of a
      credible placebo, elevated the confidence due these findings. CONCLUSIONS:
      Gradual drug withdrawal was associated with substantial hypnotic reduction at
      posttreatment and follow-up, and withdrawal side-effects were absent. When
      supplemented with CBT, participants accrued incremental self-reported, but not
      PSG, sleep benefits.

PMID- 24121098
TI  - In search for a public health leadership competency framework to support
      leadership curriculum-a consensus study.
AB  - BACKGROUND: Competency-based education is increasingly popular, especially in the
      area of continuing professional development. Many competency frameworks have been
      developed; however, few address leadership competencies for European public
      health professionals. The aim of this study was to develop a public health
      leadership competency framework to inform a leadership curriculum for public
      health professionals. The framework was developed as part of the Leaders for
      European Public Health project-supported by the EU Lifelong Learning Programme.
      METHODS: The study was carried out in three phases: a literature review,
      consensus development panel and Delphi survey. The public health leadership
      competency framework was initially developed from a literature review. A
      preliminary list of competencies was submitted to a panel of experts. Two
      consensus development panels were held to evaluate and make changes to the
      initial draft competency framework. Then two rounds of a Delphi survey were
      carried out in an effort to reach consensus. Both surveys were presented through
      Survey Monkey to members of the Association of the Schools of Public Health in
      the European Region Working Group on Innovation in Public Health Teaching and
      Education. RESULTS: The framework was developed consisting of 52 competencies
      organized into eight domains: Systems Thinking; Political Leadership;
      Collaborative Leadership: Building and Leading Interdisciplinary Teams;
      Leadership and Communication; Leading Change; Emotional Intelligence and
      Leadership in Team-based Organizations; Leadership, Organizational Learning and
      Development and Ethics and Professionalism. CONCLUSION: The framework can serve
      as a useful tool in identifying gaps in knowledge and skills, and shaping
      competency-based continuing professional development leadership curricula for
      public health professionals in Europe.

PMID- 24121099
TI  - Unlinked genetic loci control the reduced transcription of aminopeptidase N 1 and
      3 in the European corn borer and determine tolerance to Bacillus thuringiensis
      Cry1Ab toxin.
AB  - Transgenic expression of Bacillus thuringiensis (Bt) crystalline (Cry) toxins by
      crop plants result in reduced insect feeding damage, but sustainability is
      threatened by the development of resistance traits in target insect populations.
      We investigated Bt toxin resistance trait in a laboratory colony of the European
      corn borer, Ostrinia nubilalis, selected for increased survival when exposed to
      Cry1Ab and correlated survival on Cry1Ab toxin with a constitutive ~146.2 +/-
      17.3-fold reduction in midgut aminopeptidase N1 (apn1) transcript levels. A 7.1
      +/- 1.9-fold reduction apn3 transcript level was also correlated with Cry1Ab
      resistance. Quantitative trait locus (QTL) mapping identified a single major
      genome region controlling Cry1Ab resistance on linkage group 24 (LG24), and a
      minor QTL on LG27. Both QTL were independent of apn1 and apn3 loci on LG02.
      Positional mapping identified genetic markers that may assist in the
      identification of causal gene(s) within QTL intervals. This study indicates that
      genetic factor(s) may act in trans to reduce both apn1 and apn3 expression in
      Cry1Ab resistant O. nubilalis larvae, and suggest that gene regulatory pathways
      can influence Bt resistance traits. These findings show that gene interactions
      (epistasis) may influence Bt resistance in target insect populations. 

PMID- 24121100
TI  - Psychological treatment of social anxiety disorder improves body dysmorphic
      concerns.
AB  - Social anxiety disorder and body dysmorphic disorder are considered nosologically
      distinct disorders. In contrast, some cognitive models suggest that social
      anxiety disorder and body dysmorphic disorder share similar cognitive maintenance
      factors. The aim of this study was to examine the effects of psychological
      treatments for social anxiety disorder on body dysmorphic disorder concerns. In
      Study 1, we found that 12 weekly group sessions of cognitive-behavioral therapy
      led to significant decreases in body dysmorphic symptom severity. In Study 2, we
      found that an attention retraining intervention for social anxiety disorder was
      associated with a reduction in body dysmorphic concerns, compared to a placebo
      control condition. These findings support the notion that psychological
      treatments for individuals with primary social anxiety disorder improve co
      occurring body dysmorphic disorder symptoms. 

PMID- 24121101
TI  - Accumulation and toxicity of metal oxide nanoparticles in a soft-sediment
      estuarine amphipod.
AB  - Estuarine and marine sediments are a probable end point for many engineered
      nanoparticles (ENPs) due to enhanced aggregation and sedimentation in marine
      waters, as well as uptake and deposition by suspension-feeding organisms on the
      seafloor. Benthic infaunal organisms living in sediments encounter relatively
      high concentrations of pollutants and may also suffer toxic effects of ENPs. We
      tested whether three heavily used metal oxide ENPs, zinc oxide (ZnO), copper
      oxide (CuO), and nickel oxide (NiO) were toxic to an estuarine amphipod,
      Leptocheirus plumulosus. We used results from 10-day laboratory bioassays to
      estimate potential demographic impacts of ENP exposure. We also evaluated fate
      and transport pathways of the ENPs in the experiments to elucidate routes of
      uptake and exposure. Dissolved Zn was found in sediment pore water and overlying
      water samples at 10 fold the concentrations of Cu or Ni, a pattern indicative of
      the relatively high dissolution rate of ZnO ENPs compared with CuO and NiO ENPs.
      Accumulation of metals in amphipod tissues increased with exposure concentrations
      for all three ENPs, suggesting possible exposure pathways to higher taxa.
      Amphipods accumulated <=600 MUg Zn and Cu g(-1) and 1000 MUg Ni g(-1). Amphipod
      mortality increased with ZnO and CuO concentrations, but showed no significant
      increase with NiO to concentrations as high as 2000 MUg g(-1). The median lethal
      concentration in sediment (LC50) of ZnO was 763 MUg g(-1) and 868 MUg g(-1) for
      CuO ENPs. Our results indicate that ZnO and CuO ENPs, but not NiO ENPs, are toxic
      to L. plumulosus and that ZnO toxicity primarily results from Zn ion exposure
      while CuO toxicity is due to nanoparticle exposure.

PMID- 24121102
TI  - Kava chalcone, flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T
      transgenic mouse model.
AB  - Flavokawain A (FKA) is the predominant chalcone identified from the kava plant.
      We have previously shown that FKA preferentially inhibits the growth of p53
      defective bladder cancer cell lines. Here, we examined whether FKA could inhibit
      bladder cancer development and progression in vivo in the UPII-SV40T transgenic
      model that resembles human urothelial cell carcinoma (UCC) with defects in the
      p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were
      fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days
      starting at 28 days of age. More than 64% of the male mice fed with FKA
      containing food survived beyond 318 days of age, whereas only about 38% of the
      male mice fed with vehicle control food survived to that age (P = 0.0383). The
      mean bladder weights of surviving male transgenic mice with the control diet
      versus the FKA diet were 234.6 +/- 72.5 versus 96.1 +/- 69.4 mg (P = 0.0002). FKA
      was excreted primarily through the urinary tract and concentrated in the urine up
      to 8.4 MUmol/L, averaging about 38 times (males) and 15 times (females) more
      concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the
      occurrence of high-grade papillary UCC, a precursor to invasive urothelial
      cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked
      inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5,
      and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue
      of FKA-fed mice. These results suggest a potential of FKA in preventing the
      recurrence and progression of non-muscle-invasive UCC.

PMID- 24121103
TI  - Inhibition of Wee1 sensitizes cancer cells to antimetabolite chemotherapeutics in
      vitro and in vivo, independent of p53 functionality.
AB  - Inhibition of Wee1 is emerging as a novel therapeutic strategy for cancer, and
      some data suggest that cells with dysfunctional p53 are more sensitive to Wee1
      inhibition combined with conventional chemotherapy than those with functional
      p53. We and others found that Wee1 inhibition sensitizes leukemia cells to
      cytarabine. Thus, we sought to determine whether chemosensitization by Wee1
      inhibition is dependent on p53 dysfunction and whether combining Wee1 inhibition
      is tolerable and effective in vivo. Synergistic inhibition of proliferation with
      a Wee1 inhibitor in clinical development, MK1775, and cytarabine was observed in
      all acute myelogenous leukemia (AML) cell lines tested, regardless of p53
      functionality. Mechanistic studies indicate that inhibition of Wee1 abrogates the
      S-phase checkpoint and augments apoptosis induced by cytarabine. In AML and lung
      cancer cell lines, genetic disruption of p53 did not alter the cells' enhanced
      sensitivity to antimetabolites with Wee1 inhibition. Finally, mice with AML were
      treated with cytarabine and/or MK1775. The combination of MK1775 and cytarabine
      was well tolerated in mice and enhanced the antileukemia effects of cytarabine,
      including survival. Thus, inhibition of Wee1 sensitizes hematologic and solid
      tumor cell lines to antimetabolite chemotherapeutics, whether p53 is functional
      or not, suggesting that the use of p53 mutation as a predictive biomarker for
      response to Wee1 inhibition may be restricted to certain cancers and/or
      chemotherapeutics. These data provide preclinical justification for testing
      MK1775 and cytarabine in patients with leukemia.

PMID- 24121104
TI  - Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems.
AB  - BACKGROUND: Antiretroviral Therapy (ART) is currently the major therapeutic
      intervention in the treatment of AIDS. ART, however, is severely limited due to
      poor availability, high cytotoxicity, and enhanced metabolism and clearance of
      the drug molecules by the renal system. The use of nanocarriers encapsulating the
      anti-retroviral drugs may provide a solution to the aforementioned problems.
      Importantly, the application of mildly immunogenic polymeric carrier confers the
      advantage of making the nanoparticles more visible to the immune system leading
      to their efficient uptake by the phagocytes. METHODS: The saquinavir-loaded
      chitosan nanoparticles were characterized by transmission electron microscopy and
      differential scanning calorimetry and analyzed for the encapsulation efficiency,
      swelling characteristics, particle size properties, and the zeta potential.
      Furthermore, cellular uptake of the chitosan nanocarriers was evaluated using
      confocal microscopy and Flow cytometry. The antiviral efficacy was quantified
      using viral infection of the target cells. RESULTS: Using novel chitosan carriers
      loaded with saquinavir, a protease inhibitor, we demonstrate a drug encapsulation
      efficiency of 75% and cell targeting efficiency greater than 92%. As compared to
      the soluble drug control, the saquinavir-loaded chitosan carriers caused superior
      control of the viral proliferation as measured by using two different viral
      strains, NL4-3 and Indie-C1, and two different target T-cells, Jurkat and CEM
      CCR5. CONCLUSION: Chitosan nanoparticles loaded with saquinavir were
      characterized and they demonstrated superior drug loading potential with greater
      cell targeting efficiency leading to efficient control of the viral proliferation
      in target T-cells. GENERAL SIGNIFICANCE: Our data ascertain the potential of
      chitosan nanocarriers as novel vehicles for HIV-1 therapeutics.

PMID- 24121105
TI  - Carbon-14 decay as a source of non-canonical bases in DNA.
AB  - BACKGROUND: Significant experimental effort has been applied to study radioactive
      beta-decay in biological systems. Atomic-scale knowledge of this transmutation
      process is lacking due to the absence of computer simulations. Carbon-14 is an
      important beta-emitter, being ubiquitous in the environment and an intrinsic part
      of the genetic code. Over a lifetime, around 50 billion (14)C decays occur within
      human DNA. METHODS: We apply ab initio molecular dynamics to quantify (14)C
      induced bond rupture in a variety of organic molecules, including DNA base pairs.
      RESULTS: We show that double bonds and ring structures confer radiation
      resistance. These features, present in the canonical bases of the DNA, enhance
      their resistance to (14)C-induced bond-breaking. In contrast, the sugar group of
      the DNA and RNA backbone is vulnerable to single-strand breaking. We also show
      that Carbon-14 decay provides a mechanism for creating mutagenic wobble-type
      mispairs. CONCLUSIONS: The observation that DNA has a resistance to natural
      radioactivity has not previously been recognized. We show that (14)C decay can be
      a source for generating non-canonical bases. GENERAL SIGNIFICANCE: Our findings
      raise questions such as how the genetic apparatus deals with the appearance of an
      extra nitrogen in the canonical bases. It is not obvious whether or not the DNA
      repair mechanism detects this modification nor how DNA replication is affected by
      a non-canonical nucleobase. Accordingly, (14)C may prove to be a source of
      genetic alteration that is impossible to avoid due to the universal presence of
      radiocarbon in the environment.

PMID- 24121106
TI  - Differential response of DU145 and PC3 prostate cancer cells to ionizing
      radiation: role of reactive oxygen species, GSH and Nrf2 in radiosensitivity.
AB  - BACKGROUND: Radioresistance is the major impediment in radiotherapy of many
      cancers including prostate cancer, necessitating the need to understand the
      factors contributing to radioresistance in tumor cells. In the present study, the
      role of cellular redox and redox sensitive transcription factor, Nrf2 in the
      radiosensitivity of prostate cancer cell lines PC3 and DU145, has been
      investigated. MATERIALS AND METHODS: Differential radiosensitivity of PC3 and
      DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay.
      Their redox status was measured using DCFDA and DHR probes. Expression of Nrf2
      and its dependent genes was measured by EMSA and real time PCR. Knockdown studies
      were done using shRNA transfection. RESULTS: PC3 and DU145 cells differed
      significantly in their radiosensitivity as observed by clonogenic survival,
      apoptosis and neutral comet assays. Both basal and inducible levels of ROS were
      higher in PC3 cells than that of DU145 cells. DU145 cells showed higher level of
      basal GSH content and GSH/GSSG ratio than that of PC3 cells. Further, significant
      increase in both basal and induced levels of Nrf2 and its dependent genes was
      observed in DU145 cells. Knock-down experiments and pharmacological intervention
      studies revealed the involvement of Nrf2 in differential radio-resistance of
      these cells. CONCLUSION: Cellular redox status and Nrf2 levels play a causal role
      in radio-resistance of prostate cancer cells. GENERAL SIGNIFICANCE: The pivotal
      role Nrf2 has been shown in the radioresistance of tumor cells and this study
      will further help in exploiting this factor in radiosensitization of other tumor
      cell types.

PMID- 24121108
TI  - An ectotherm homologue of human predicted gene NAT16 encodes histidine N
      acetyltransferase responsible for Nalpha-acetylhistidine synthesis.
AB  - BACKGROUND: Nalpha-Acetylhistidine (NAH) is present in very high concentrations
      exclusively in the brain and lens of ectothermic vertebrates, including ray
      finned fishes, amphibians and reptiles, and not in those of endothermic birds and
      mammals. Although NAH is known to be synthesized from l-His and acetyl-CoA by
      histidine N-acetyltransferase (HISAT; EC 2.3.1.33), the gene encoding HISAT has
      remained unknown for any organism. METHODS: HISAT was purified from the blue
      mackerel brain, and its partial amino acid sequences were analyzed using mass
      spectrometry and Edman degradation. Using the sequence information, the
      corresponding gene was cloned and sequenced. Recombinant proteins encoded by the
      fish gene and its human homologue were expressed in a cell-free translation
      system. RESULTS: HISAT was identified to be a protein encoded by a fish homologue
      of the human predicted gene NAT16 (N-acetyltransferase 16). HISAT is an unstable
      enzyme that is rapidly and irreversibly inactivated during preincubation at 37
      degrees C in the absence of acetyl-CoA. In fish brain, the HISAT gene is
      expressed as two splice variants containing an identical ORF but differing
      lengths of 5'-UTR. Both variants are expressed exclusively in the fish brain and
      lens. Interestingly, the recombinant human NAT16 protein, unlike the recombinant
      fish HISAT, has only trace enzyme activity for NAH synthesis. CONCLUSIONS: These
      results propose that the function of mammalian NAT16 has been altered from l-His
      acetylation (NAH synthesis) to another different biological role. GENERAL
      SIGNIFICANCE: The molecular identification of HISAT will allow progress in the
      understanding of the physiological function of NAH in ectothermic vertebrates.

PMID- 24121107
TI  - Dissecting cobamide diversity through structural and functional analyses of the
      base-activating CobT enzyme of Salmonella enterica.
AB  - BACKGROUND: Cobamide diversity arises from the nature of the nucleotide base.
      Nicotinate mononucleotide (NaMN):base phosphoribosyltransferases (CobT)
      synthesize alpha-linked riboside monophosphates from diverse nucleotide base
      substrates (e.g., benzimidazoles, purines, phenolics) that are incorporated into
      cobamides. METHODS: Structural investigations of two members of the CobT family
      of enzymes in complex with various substrate bases as well as in vivo and vitro
      activity analyses of enzyme variants were performed to elucidate the roles of key
      amino acid residues important for substrate recognition. RESULTS: Results of in
      vitro and in vivo studies of active-site variants of the Salmonella enterica CobT
      (SeCobT) enzyme suggest that a catalytic base may not be required for catalysis.
      This idea is supported by the analyses of crystal structures that show that two
      glutamate residues function primarily to maintain an active conformation of the
      enzyme. In light of these findings, we propose that proper positioning of the
      substrates in the active site triggers the attack at the C1 ribose of NaMN.
      CONCLUSION: Whether or not a catalytic base is needed for function is discussed
      within the framework of the in vitro analysis of the enzyme activity.
      Additionally, structure-guided site-directed mutagenesis of SeCobT broadened its
      substrate specificity to include phenolic bases, revealing likely evolutionary
      changes needed to increase cobamide diversity, and further supporting the
      proposed mechanism for the phosphoribosylation of phenolic substrates. GENERAL
      SIGNIFICANCE: Results of this study uncover key residues in the CobT enzyme that
      contribute to the diversity of cobamides in nature.

PMID- 24121109
TI  - Activation of PRMT1 and PRMT5 mediates hypoxia- and ischemia-induced apoptosis in
      human lung epithelial cells and the lung of miniature pigs: the role of p38 and
      JNK mitogen-activated protein kinases.
AB  - Severe hypoxic and ischemic injury leads to primary graft dysfunction after lung
      transplantation. Arginine methylation, which is responsible for the regulation of
      a variety of biological functions, is mediated by protein arginine methylation
      transferases (PRMTs). This study examined the role of hypoxia in PRMT activation
      in A549 human lung epithelial cells, as well as the role of ischemia in PRMT
      activation in the lung of miniature pigs. In A459 cells, hypoxia increased the
      expression of PRMT1 and PRMT5, and overexpression of PRMT1 and PRMT5 induced
      apoptosis. The transfection of PRMT1 and PRMT5 small interfering RNA (siRNA)
      prevented hypoxia-inducible factor (HIF)-1alpha expression and apoptosis in A549
      cells. Hypoxia-induced expression of PRMT1 and PRMT5 was blocked by p38 and JNK
      mitogen-activated protein kinase (MAPK) inhibitors, but not by an inhibitor of
      extracellular signal-regulated kinases (ERK) 1/2. In the lungs of miniature pigs,
      ischemia stimulated PRMT1 and PRMT5 expression and induced phosphorylation of p38
      MAPK (p-p38), phosphorylation of JNK (p-JNK), and apoptotic molecules. These
      results demonstrate that PRMT1 and PRMT5 are involved in hypoxia and ischemia
      induced apoptosis via p-p38 MAPK and p-JNK in in vitro and in vivo models.

PMID- 24121110
TI  - Sequence, phylogenetic and variant analyses of antithrombin III.
AB  - Antithrombin III (ATIII) performs a critical anticoagulant function by precluding
      the activation of blood clotting proteinases, aided by its two cofactors, heparin
      and heparan sulfate. Though several studies have been carried out on
      physiological, biochemical and structural perspectives on ATIII, so far there are
      limited studies on the molecular evolution of ATIII. Herein, we carried out
      molecular phylogenetic analyses of ATIII genes, combining gene structures,
      synteny and sequence-structural features for ATIII spanning 50 vertebrate
      genomes. ATIII is maintained over 450 MY on same genomic loci in vertebrates with
      few changes in ray-finned fishes and lost one intron 262c in tetrapods and
      coelacanth. In ray-finned fishes, ATIII gene has additional intron at the
      position 262c, which shared by group V1 members, corroborating that it is lost in
      other vertebrates and also in lobed-finned fish coelacanth (Latimeria chalumnae).
      We found that heparin binding basic residues, hD helix, three pairs of Cys-Cys
      salt bridges, N-glycosylation sites, serpin motifs and inhibitory reactive center
      loop (RCL) of ATIII protein are highly conserved. Using 1092 human genomes
      available from 1000G project, we also compiled 1997 ATIII variants, which reveals
      76.2% single nucleotide polymorphisms (SNPs), 11.8% deletions and 8.1% insertions
      as three major classes of gene variations. These understandings may have medical
      importance as well. 

PMID- 24121111
TI  - [Community-based surveillance of maternal, infant, and child (under-5) mortality
      in the health district of Tanguieta (Benin) from 2006 through 2010].
AB  - In Benin, maternal, infant (under 1 year) and child (under 5 years) mortality
      rates are measured every five years by national demographic health surveys. These
      provide data only at the national level, however. Because they do not reveal
      local disparities, they provide no information about how to target healthcare
      interventions. To overcome these limitations and evaluate the primary healthcare
      program in the Tanguieta district, the UniCredit Foundation set up a system for
      monitoring maternal and under-5 deaths in partnership with the local authorities.
      The system costs ? 10,500/year, and is based on a network of 155 community
      healthcare workers (sentinels) responsible for counting all maternal and
      childhood deaths. From 2006 through 2010, the maternal mortality rate (MMR)
      decreased from 531 to 220 deaths per 100,000 live births; 47% of these deaths
      occurred at home. Mortality among children younger than 5 years (U-5) was 76 per
      1,000 live births in 2006 and 77 per 1,000 live births in 2010), and 46% of the
      children died at home. A quality control study of our system in February 2011
      showed that its sensitivity was good (95%) for MMR (232 deaths per 100,000
      livebirths in 2010), but poor (48%) for U-5 mortality (155 deaths per 1,000
      livebirths in 2010) and U-1 mortality (74 per 1,000 livebirths, sensitivity 47%).
      We conclude that the system is adequate for assessing the effect of maternal
      healthcare interventions but has some weaknesses in relation to childhood
      mortality, mainly because of local social customs and the fact that childhood
      deaths appear to have less resonance. Poor coverage of isolated villages may also
      explain this partially unsatisfactory performance. Our intervention has
      nonetheless contributed to improving the quality of basic data collection in the
      district.

PMID- 24121112
TI  - Allopregnanolone: state of the art.
AB  - Allopregnanolone, a neuroactive steroid derived from progesterone, is synthesized
      within the nervous tissue, by means of specific enzymes. Contrary to progesterone
      and its first metabolite dihydroprogesterone, allopregnanolone is able to
      interact with GABA-A receptor and not with the classical progesterone receptor.
      This suggests that the effect of progesterone administration may be due to
      activation of progesterone receptor, or of GABA-A receptor, or both. However,
      this is rarely considered in the experimental studies. Here we summarize and
      discuss the hot topics involving the actions of allopregnanolone within the
      nervous tissue. One major role of this neuroactive steroid is neuroprotection in
      case of lesion, ischemia or peripheral neuropathies (i.e., diabetes). In
      addition, allopregnanolone may reduce the symptoms of neurodegenerative diseases
      (e.g., Alzheimer, Parkinson, Niemann-Pick type C, multiple sclerosis) in animal
      models and now translational studies are developed for its therapeutic use.
      Allopregnanolone may exert a beneficial effect also in case of neuropathic pain
      and it is also a potential candidate for the treatment of mood and anxiety
      disorders. Finally, this neuroactive steroid seems to have important
      physiological roles in the early differentiation of some neural circuits (in
      particular at hippocampal level), and to reduce stress during pregnancy. In
      conclusion, it appears that allopregnanolone is a key regulator of physiological
      functions and may have interesting therapeutic perspectives for neurodegenerative
      and psychiatric disorders. 

PMID- 24121113
TI  - Commercial viability of CNS drugs: balancing the risk/reward profile.
AB  - CNS has historically been a formidable therapeutic area in which to innovate
      owing to biological (e.g., complex neurobiology, difficulty reaching the target),
      as well as clinical (e.g., subjective clinical endpoints, high placebo response,
      lack of biomarkers) challenges. In the current market where many of the larger
      diseases are dominated by a generic standard of care, commercial challenges now
      make the triple threat of scientific-clinical-commercial risk too much for many
      players to tackle. However, opportunities do exist for smaller biotech companies
      to concentrate on narrowly focused patient populations associated with high unmet
      need for which risk can be tightly defined. In CNS, there are two major areas to
      balance the risk/reward profile and create commercially viable opportunities: To
      realize value, all companies (start-ups and big players) must define, measure and
      quantify clear and meaningful value to all stakeholders: physicians, patients,
      caregivers and payers. 

PMID- 24121114
TI  - Subtle microstructural changes of the cerebellum in a knock-in mouse model of
      DYT1 dystonia.
AB  - The dystonias are a group of disorders characterized by involuntary twisting and
      repetitive movements. DYT1 dystonia is an inherited form of dystonia caused by a
      mutation in the TOR1A gene, which encodes torsinA. TorsinA is expressed in many
      regions of the nervous system, and the regions responsible for causing dystonic
      movements remain uncertain. Most prior studies have focused on the basal ganglia,
      although there is emerging evidence for abnormalities in the cerebellum too. In
      the current studies, we examined the cerebellum for structural abnormalities in a
      knock-in mouse model of DYT1 dystonia. The gross appearance of the cerebellum
      appeared normal in the mutant mice, but stereological measures revealed the
      cerebellum to be 5% larger in mutant compared to control mice. There were no
      changes in the numbers of Purkinje cells, granule cells, or neurons of the deep
      cerebellar nuclei. However, Golgi histochemical studies revealed Purkinje cells
      to have thinner dendrites, and fewer and less complex dendritic spines. There
      also was a higher frequency of heterotopic Purkinje cells displaced into the
      molecular layer. These results reveal subtle structural changes of the cerebellum
      that are similar to those reported for the basal ganglia in the DYT1 knock-in
      mouse model. 

PMID- 24121115
TI  - Pacemaker GABA synaptic activity may contribute to network synchronization in
      pediatric cortical dysplasia.
AB  - Spontaneous pacemaker gamma-aminobutyric acid (GABA) receptor-mediated synaptic
      activity (PGA) occurs in a subset of tissue samples from pediatric epilepsy
      surgery patients. In the present study, based on single-cell electrophysiological
      recordings from 120 cases, we describe the etiologies, cell types, and primary
      electrophysiological features of PGA. Cells displaying PGA occurred more
      frequently in the areas of greatest anatomical abnormality in cases of focal
      cortical dysplasia (CD), often associated with hemimegalencephaly (HME), and only
      rarely in non-CD etiologies. PGA was characterized by rhythmic synaptic events (5
      10Hz) and was observed in normal-like, dysmorphic cytomegalic, and immature
      pyramidal neurons. PGA was action potential-dependent, mediated by GABAA
      receptors, and unaffected by antagonism of glutamate receptors. We propose that
      PGA is a unique electrophysiological characteristic associated with CD and HME.
      It could represent an abnormal signal that may contribute to epileptogenesis in
      malformed postnatal cortex by facilitating pyramidal neuron synchrony. 

PMID- 24121116
TI  - Region-specific deficits in dopamine, but not norepinephrine, signaling in a
      novel A30P alpha-synuclein BAC transgenic mouse.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder classically
      characterized by the death of dopamine (DA) neurons in the substantia nigra pars
      compacta and by intracellular Lewy bodies composed largely of alpha-synuclein.
      Approximately 5-10% of PD patients have a familial form of Parkinsonism,
      including mutations in alpha-synuclein. To better understand the cell-type
      specific role of alpha-synuclein on DA neurotransmission, and the effects of the
      disease-associated A30P mutation, we generated and studied a novel transgenic
      model of PD. We expressed the A30P mutant form of human alpha-synuclein in a
      spatially-relevant manner from the 111kb SNCA genomic DNA locus on a bacterial
      artificial chromosome (BAC) insert on a mouse null (Snca-/-) background. The BAC
      transgenic mice expressed alpha-synuclein in tyrosine hydroxylase-positive
      neurons and expression of either A30P alpha-synuclein or wildtype alpha-synuclein
      restored the sensitivity of DA neurons to MPTP in resistant Snca-/- animals. A30P
      alpha-synuclein mice showed no Lewy body-like aggregation, and did not lose
      catecholamine neurons in substantia nigra or locus coeruleus. However, using
      cyclic voltammetry at carbon-fiber microelectrodes we identified a deficit in
      evoked DA release in the caudate putamen, but not in the nucleus accumbens, of
      SNCA-A30P Snca-/- mice but no changes to release of another catecholamine,
      norepinephrine (NE), in the NE-rich ventral bed nucleus of stria terminalis. SNCA
      A30P Snca-/- mice had no overt behavioral impairments but exhibited a mild
      increase in wheel-running. In summary, this refined PD mouse model shows that
      A30P alpha-synuclein preferentially perturbs the dopaminergic system in the
      dorsal striatum, reflecting the region-specific change seen in PD. 

PMID- 24121118
TI  - Transient OGG1, APE1, PARP1 and Polbeta expression in an Alzheimer's disease
      mouse model.
AB  - Alzheimer's disease (AD) is a disease of major public health significance, whose
      pathogenesis is strongly linked to the presence of fibrillar aggregates of
      amyloid-beta (Abeta) in the aging human brain. We exploited the transgenic (Tg)
      ArcSwe mouse model for human AD to explore whether oxidative stress and the
      capacity to repair oxidative DNA damage via base excision repair (BER) are
      related to Abeta pathology in AD. Tg-ArcSwe mice express variants of Abeta,
      accumulating senile plaques at 4-6 months of age, and develop AD-like
      neuropathology as adult animals. The relative mRNA levels of genes encoding BER
      enzymes, including 8-oxoguanine glycosylase (OGG1), AP endonuclease 1 (APE1),
      polymerase beta (Polbeta) and poly(ADP-ribose) polymerase 1 (PARP1), were
      quantified in various brain regions of 6 weeks, 4 months and 12 months old mice.
      The results show that OGG1 transcriptional expression was higher, and APE1
      expression lower, in 4 months old Tg-ArcSwe than in wildtype (wt) mice.
      Furthermore, Polbeta transcriptional expression was significantly lower in
      transgenic 12 months old mice than in wt. Transcriptional profiling also showed
      that BER repair capacity vary during the lifespan in Tg-ArcSwe and wt mice. The
      BER expression pattern in Tg-ArcSwe mice thus reflects responses to oxidative
      stress in vulnerable brain structures. 

PMID- 24121117
TI  - Hyperactivity and cortical disinhibition in mice with restricted expression of
      mutant huntingtin to parvalbumin-positive cells.
AB  - Recent evidence suggests that interneurons are involved in the pathophysiology of
      Huntington Disease (HD). Abnormalities in the function of interneurons expressing
      the calcium buffer parvalbumin (PV) have been observed in multiple mouse models
      of HD, although it is not clear how PV-positive interneuron dysfunction
      contributes to behavioral and synaptic deficits. Here, we use the cre-lox system
      to drive expression of mutant huntingtin (mthtt) in parvalbumin (PV)-positive
      neurons and find that mutant mice exhibit diffuse mthtt immunoreactivity in PV
      rich areas at 10months of age and mthtt aggregates in PV-positive processes at
      24months of age. At midlife, mutant mice are hyperactive and display impaired
      GABA release in the motor cortex, characterized by reduced miniature inhibitory
      events and severely blunted responses to gamma frequency stimulation, without a
      loss of PV-positive interneurons. In contrast, 24month-old mutant mice show
      normalized behavior and responses to gamma frequency stimulation, possibly due to
      compensatory changes in pyramidal neurons or the formation of inclusions with
      age. These data indicate that mthtt expression in PV-positive neurons is
      sufficient to drive a hyperactive phenotype and suggest that mthtt-mediated
      dysfunction in PV-positive neuronal populations could be a key factor in the
      hyperkinetic behavior observed in HD. Further clarification of the roles for
      specific PV-positive populations in this phenotype is warranted to definitively
      identify cellular targets for intervention. 

PMID- 24121119
TI  - Red meat and cancer risk in a network of case-control studies focusing on cooking
      practices.
AB  - BACKGROUND: Consumption of red meat has been related to increased risk of several
      cancers. Cooking methods could modify the magnitude of this association, as
      production of chemicals depends on the temperature and duration of cooking.
      METHODS: We analyzed data from a network of case-control studies conducted in
      Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and
      pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463
      colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian,
      1294 prostate and 767 renal cancer cases. Controls included 11 656 patients
      admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence
      intervals (CIs) were estimated by multiple logistic regression models, adjusted
      for known confounding factors. RESULTS: Daily intake of red meat was
      significantly associated with the risk of cancer of the oral cavity and pharynx
      (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29;
      95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46;
      95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95%
      CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95%
      CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29;
      95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of
      oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52;
      95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by
      roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to
      cooking methods emerged for other cancers. Nonetheless, significant associations
      with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97;
      95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our
      analysis confirmed red meat consumption as a risk factor for several cancer
      sites, with a limited impact of cooking methods. These findings, thus, call for a
      limitation of its consumption in populations of Western countries.

PMID- 24121120
TI  - No improvement in median survival for patients with metastatic gastric cancer
      despite increased use of chemotherapy.
AB  - BACKGROUND: Gastric cancer often presents in a metastasized stage. We conducted a
      population-based study to evaluate trends in systemic treatment and survival of
      metastatic noncardia gastric cancer. PATIENTS AND METHODS: All patients with
      noncardia adenocarcinoma of the stomach, diagnosed between 1990 and 2011 in the
      Eindhoven Cancer Registry area in the Netherlands were included (N = 4797). We
      conducted multivariable logistic regression analysis to evaluate trends in
      administration of palliative chemotherapy and multivariable proportional hazards
      regression analyses to evaluate trends in crude overall survival. RESULTS: The
      proportion of patients presenting with metastatic gastric cancer increased from
      24% in 1990 to 44% in 2011 (P < 0.0001). The use of palliative chemotherapy
      increased, from 5% in 1990 to 36% in 2011, with a strong increase in particular
      after 2006 (P < 0.0001). Younger patients [<50 years: adjusted odds ratio (ORadj)
      3.9, P < 0.001; 50-59 years: ORadj 1.7, P = 0.01] and patients with a high
      socioeconomic status (ORadj 1.7, P = 0.01) more often received chemotherapy. In
      contrast, older patients (70-79 years: ORadj 0.3, P < 0.001; 80+ years: ORadj
      0.02, P < 0.001), patients with comorbidity (ORadj 0.6, P = 0.03), linitis
      plastica (ORadj 0.5, P = 0.03) and multiple distant metastases (ORadj 0.5, P =
      0.01) were less often treated with chemotherapy. A large hospital variation was
      observed in the administration of palliative chemotherapy (9%-27%). Median
      overall survival remained constant between 15 [95% confidence interval (CI) 11.9
      17.7] and 17 (95% CI 15.0-20.0) weeks (P = 0.10). CONCLUSIONS: The increased
      administration of chemotherapy in patients with metastatic gastric cancer did not
      lead to an increase in population-based overall survival. Identification of the
      subgroup of patients which benefits from palliative chemotherapy is of utmost
      importance to avoid unnecessary treatment.

PMID- 24121121
TI  - An individual patient-data comparison of combined modality therapy and ABVD alone
      for patients with limited-stage Hodgkin lymphoma.
AB  - BACKGROUND: Treatment options for patients with nonbulky stage IA-IIA Hodgkin
      lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin,
      vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT),
      and chemotherapy with ABVD alone. There are no mature randomized data comparing
      ABVD with CMT using modern radiation techniques. PATIENTS AND METHODS: Using
      German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6
      databases, we identified 588 patients who met mutually inclusive eligibility
      criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We
      evaluated time to progression (TTP), progression-free (PFS) and overall survival,
      including in three predefined exploratory subset analyses. RESULTS: With median
      follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were
      for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI)
      0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall
      survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset
      analysis including HD10 eligible patients who achieved complete response (CR) or
      unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87%
      (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96%
      versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8
      year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95%
      versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). CONCLUSIONS: In patients
      with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control
      than ABVD alone, especially among those not achieving complete response after two
      cycles of ABVD. Within the follow-up duration evaluated, overall survivals were
      similar. Longer follow-up is required to understand the implications of radiation
      and chemotherapy-related late effects. CLINICAL TRIALS: The trials included in
      this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 -
      NCT00264953, HD.6 - NCT00002561.

PMID- 24121123
TI  - Stereoselective alpha-glycosylation of C(6)-hydroxyl myo-inositols via nickel
      catalysis-application to the synthesis of GPI anchor pseudo-oligosaccharides.
AB  - Glycosylphosphatidyl inositol (GPI) anchors play a key role in many eukaryotic
      biological pathways. Stereoselective synthesis of GPI anchor analogues have
      proven to be critical for probing the biosynthesis, structure, and biological
      properties of these compounds. Challenges that have emerged from these efforts
      include the preparation of the selectively protected myo-inositol building blocks
      and the stereoselective construction of glucosamine alpha-linked myo-inositol
      containing pseudodisaccharide units. Herein, we describe the effectiveness of the
      cationic nickel(II) catalyst, Ni(4-F-PhCN)4(OTf)2, at promoting selective
      formation of 1,2-cis-2-amino glycosidic bonds between the C(2)-N-substituted
      benzylideneamino trihaloacetimidate donors and C(6)-hydroxyl myo-inositol
      acceptors. This catalytic coupling process allows rapid access to
      pseudosaccharides of GPI anchors in good yields and with excellent levels of
      alpha-selectivity (alpha:beta=10:1-20:1). In stark contrast, activation of
      trichloroacetimidate donors containing the C(2)-N-substituted benzylidene group
      with TMSOTf and BF3(.)OEt2 provided the desired pseudodisaccharides as a 1:1
      mixture of alpha- and beta-isomers. 

PMID- 24121122
TI  - Functional characterization of a full length pregnane X receptor, expression in
      vivo, and identification of PXR alleles, in zebrafish (Danio rerio).
AB  - The pregnane X receptor (PXR) (nuclear receptor NR1I2) is a ligand activated
      transcription factor, mediating responses to diverse xenobiotic and endogenous
      chemicals. The properties of PXR in fish are not fully understood. Here we report
      on cloning and characterization of full-length PXR of zebrafish, Danio rerio, and
      pxr expression in vivo. Initial efforts gave a cDNA encoding a 430 amino acid
      protein identified as zebrafish pxr by phylogenetic and synteny analysis. The
      sequence of the cloned Pxr DNA binding domain (DBD) was highly conserved, with
      74% identity to human PXR-DBD, while the ligand-binding domain (LBD) of the
      cloned sequence was only 44% identical to human PXR-LBD. Sequence variation among
      clones in the initial effort prompted sequencing of multiple clones from a single
      fish. There were two prominent variants, one sequence with S183, Y218 and H383
      and the other with I183, C218 and N383, which we designate as alleles pxr*1
      (nr1i2*1) and pxr*2 (nr1i2*2), respectively. In COS-7 cells co-transfected with a
      PXR-responsive reporter gene, the full-length Pxr*1 (the more common variant) was
      activated by known PXR agonists clotrimazole and pregnenolone 16alpha
      carbonitrile but to a lesser extent than the full-length human PXR. Activation of
      full-length Pxr*1 was only 10% of that with the Pxr*1 LBD. Quantitative real time
      PCR analysis showed prominent expression of pxr in liver and eye, as well as
      brain and intestine of adult zebrafish. The pxr was expressed in heart and kidney
      at levels similar to that in intestine. The expression of pxr in liver was weakly
      induced by ligands for mammalian PXR or constitutive androstane receptor (NR1I3).
      The results establish a foundation for PXR studies in this vertebrate model. PXR
      allelic variation and the differences between the full-length PXR and the LBD in
      reporter assays have implications for assessing the action of PXR ligands in
      zebrafish. 

PMID- 24121124
TI  - Broad-spectrum anti-tumor and anti-metastatic DNA vaccine based on p62-encoding
      vector.
AB  - Autophagy plays an important role in neoplastic transformation of cells and in
      resistance of cancer cells to radio- and chemotherapy. p62 (SQSTM1) is a key
      component of autophagic machinery which is also involved in signal transduction.
      Although recent empirical observations demonstrated that p62 is overexpressed in
      variety of human tumors, a mechanism of p62 overexpression is not known. Here we
      report that the transformation of normal human mammary epithelial cells with
      diverse oncogenes (RAS, PIK3CA and Her2) causes marked accumulation of p62. Based
      on this result, we hypothesized that p62 may be a feasible candidate to be an
      anti-cancer DNA vaccine. Here we performed a preclinical study of a novel DNA
      vaccine encoding p62. Intramuscularly administered p62-encoding plasmid induced
      anti-p62 antibodies and exhibited strong antitumor activity in four models of
      allogeneic mouse tumors - B16 melanoma, Lewis lung carcinoma (LLC), S37 sarcoma,
      and Ca755 breast carcinoma. In mice challenged with Ca755 cells, p62 treatment
      had dual effect: inhibited tumor growth in some mice and prolonged life in those
      mice which developed tumor size similar to control. P62-encoding plasmid has
      demonstrated its potency both as a preventive and therapeutic vaccine.
      Importantly, p62 vaccination drastically suppressed metastasis formation: in B16
      melanoma where tumor cells where injected intravenously, and in LLC and S37
      sarcoma with spontaneous metastasis. Overall, we conclude that a p62-encoding
      vector(s) constitute(s) a novel, effective broad-spectrum antitumor and anti
      metastatic vaccine feasible for further development and clinical trials. 

PMID- 24121125
TI  - Phylogenomic analyses support the bifurcation of ciliates into two major clades
      that differ in properties of nuclear division.
AB  - Ciliates are a diverse assemblage of eukaryotes that have been the source of many
      discoveries including self-splicing RNAs, telomeres and trans-splicing. While
      analyses of ciliate morphology have given rise to robust hypotheses on relatively
      shallow level relationships, the deeper evolutionary history of ciliates is
      largely unknown. This is in part because studies to date have focused on only a
      single locus, small subunit ribosomal DNA (SSU-rDNA). In the present study, we
      use a taxon-rich strategy based on multiple loci from GenBank and recently
      completed transcriptomes to assess deep phylogenetic relationships among
      ciliates. Our phylogenomic data set includes up to 537 taxa, all of which have
      been sampled for SSU-rDNA and a subset of which have LSU-rDNA and up to 7 protein
      coding sequences. Analyses of these data support the bifurcation of ciliates as
      suggested by SSU-rDNA, with one major clade defined by having somatic macronuclei
      that divide with intranuclear microtubules (Intramacronucleata) and the other
      clade containing lineages that either divide their macronuclei with microtubules
      external to the macronucleus or are unable to divide their macronuclei
      (Postciliodesmatophora). These multigene phylogenies provide a robust framework
      for interpreting the evolution of innovations across the ciliate tree of life. 

PMID- 24121127
TI  - Induced pluripotent stem cells: current progress and future perspectives.
      Preface.

PMID- 24121128
TI  - Classical aversive conditioning induces increased expression of mature-BDNF in
      the hippocampus and amygdala of pigeons.
AB  - The expression of brain-derived neurotrophic factor (BDNF), which is found in the
      pro-BDNF, truncated-BDNF and mature-BDNF isoforms, changes with learning. Mature
      BDNF shows a peak of late expression in the hippocampus that is involved in the
      persistence of aversive memory in rodents. However, the role of BDNF in the
      hippocampal synaptic mechanisms involved in the classical conditioning aversive
      memory in birds still needs clarification. This study investigated the late
      expression of BDNF in the hippocampus and amygdala of pigeons trained with tone
      shock conditioning and the effects of intra-hippocampal infusion of anisomycin
      (Ani) in these changes. Seven days after implantation of intra-hippocampal
      microcannulae, adult pigeons trained with three tone-shock pairings were assigned
      to one of three groups: Conditioning and Ani (CondANI), Conditioning and saline
      vehicle (CondSAL) and Conditioning only (Cond). NAIVE group had no treatment or
      conditioning. Homogenates of tissues from the hippocampus and amygdala, obtained
      12h after training, were used to determine the content of mature-BDNF, truncated
      BDNF and pro-BDNF using Western blotting. Higher values for mature-BDNF than for
      truncated- and pro-BDNF content were seen in the hippocampus of Cond and CondSAL
      birds, but not in the hippocampus of CondANI or NAIVE birds (p<0.05). The values
      of mature-BDNF in the amygdala of all the three conditioned groups were higher
      than those observed for truncated- and pro-BDNF (p<0.05), which indicates that
      the activation of this protein in the amygdala was not affected by the infusion
      of Ani in the hippocampus. The data indicate that the tone-shock conditioning
      induced the activation of molecular pathways of BDNF in the hippocampus and
      amygdala of the pigeons. The decreases in the content of truncated- and pro-BDNF
      isoforms found in conditioned pigeons may suggest cleavage mechanisms induced by
      the training. Our data confirm previous observations of rodent studies and extend
      these observations to pigeons, revealing that, in spite of the anatomical
      differences between the hippocampus of rodents and pigeons, there are functional
      and molecular mechanisms that are conservative between the species. 

PMID- 24121126
TI  - Pooled analysis of iron-related genes in Parkinson's disease: association with
      transferrin.
AB  - Pathologic features of Parkinson's disease (PD) include death of dopaminergic
      neurons in the substantia nigra, presence of alpha-synuclein containing Lewy
      bodies, and iron accumulation in PD-related brain regions. The observed iron
      accumulation may be contributing to PD etiology but it also may be a byproduct of
      cell death or cellular dysfunction. To elucidate the possible role of iron
      accumulation in PD, we investigated genetic variation in 16 genes related to iron
      homeostasis in three case-control studies from the United States, Australia, and
      France. After screening 90 haplotype tagging single nucleotide polymorphisms
      (SNPs) within the genes of interest in the US study population, we investigated
      the five most promising gene regions in two additional independent case-control
      studies. For the pooled data set (1289 cases, 1391 controls) we observed a
      protective association (OR=0.83, 95% CI: 0.71-0.96) between PD and a haplotype
      composed of the A allele at rs1880669 and the T allele at rs1049296 in
      transferrin (TF; GeneID: 7018). Additionally, we observed a suggestive protective
      association (OR=0.87, 95% CI: 0.74-1.02) between PD and a haplotype composed of
      the G allele at rs10247962 and the A allele at rs4434553 in transferrin receptor
      2 (TFR2; GeneID: 7036). We observed no associations in our pooled sample for
      haplotypes in SLC40A1, CYB561, or HFE. Taken together with previous findings in
      model systems, our results suggest that TF or a TF-TFR2 complex may have a role
      in the etiology of PD, possibly through iron misregulation or mitochondrial
      dysfunction within dopaminergic neurons. 

PMID- 24121129
TI  - Rumination mediates the relationship between structural variations in
      ventrolateral prefrontal cortex and sensitivity to negative life events.
AB  - Individuals have different levels of stress sensitivity. An individual's
      predisposition to experience negative life events (NLEs) may make him/her more
      vulnerable to a series of psychopathological and physical diseases. However, the
      neuroanatomical correlates of individual differences in sensitivity to NLEs
      remain unknown. In this study, voxel-based morphometry was used to identify the
      gray matter (GM) associations of individual differences in sensitivity to NLEs
      measured by adolescent self-rating life events checklist. Results showed that
      there was a positive association between individual NLEs sensitivity and regional
      GM volume (rGMV) in the ventrolateral prefrontal cortex (VLPFC). GM was mostly
      evident in the left frontal operculum and a small part of the left middle frontal
      gyrus. This region was thought to play an important role in introception.
      Importantly, our study revealed that rumination served as a mediator between the
      rGMV of the VLPFC and individual NLEs sensitivity. These findings suggest that
      people with greater VLPFC might be more inclined to ruminate and the ruminative
      response style might make them more sensitive to NLEs. 

PMID- 24121130
TI  - Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing
      cellular distribution of choline acetyltransferase in cholinergic interneurons in
      rats.
AB  - Cholinergic interneurons, which provide the main source of acetylcholine (ACh) in
      the striatum, control the striatal local circuits and deeply involve in the
      pathogenesis of neurodegenerative diseases. Glycogen synthase kinase-3 (GSK-3) is
      a crucial kinase with diverse fundamental functions and accepted that
      deregulation of GSK-3 activity also plays important roles in diverse
      neurodegenerative diseases. However, up to now, there is no direct proof
      indicating whether GSK-3 activation is responsible for cholinergic dysfunction.
      In the present study, with combined intracerebroventricular injection of
      Wortmannin and GF-109203X, we activated GSK-3 and demonstrated the increased
      phosphorylation level of microtubule-associated protein tau and neurofilaments
      (NFs) in the rat striatum. The activated GSK-3 consequently decreased ACh level
      in the striatum as a result of the reduction of choline acetyltransferase (ChAT)
      activity. The alteration of ChAT activity was due to impaired ChAT distribution
      rather than its expression. Furthermore, we proved that cellular ChAT
      distribution was dependent on low phosphorylation level of NFs. Nevertheless, the
      cholinergic dysfunction in the striatum failed to induce significant neuronal
      number reduction. In summary, our data demonstrates the link between GSK-3
      activation and cholinergic dysfunction in the striatum and provided beneficial
      evidence for the pathogenesis study of relevant neurodegenerative diseases. 

PMID- 24121131
TI  - Scatter hoarding and hippocampal cell proliferation in Siberian chipmunks.
AB  - Food hoarding, especially scatter hoarding and retrieving food caches, requires
      spatial learning and memory and is an adaptive behavior important for an animal's
      survival and reproductive success. In the present study, we examined the effects
      of hoarding behavior on cell proliferation and survival in the hippocampus of
      male and female Siberian chipmunks (Tamias sibiricus). We found that chipmunks in
      a semi-natural enclosure displayed hoarding behavior with large individual
      variations. Males ate more scatter-hoarded seeds than females. In addition, the
      display of hoarding behavior was associated with increased cell proliferation in
      the hippocampus and this increase occurred in a brain region-specific manner.
      These data provide further evidence to support the notion that new cells in the
      adult hippocampus are affected by learning and memory tasks and may play an
      important role in adaptive behavior. 

PMID- 24121133
TI  - Development and validation of a real-time two-step RT-qPCR TaqMan((r)) assay for
      quantitation of Sacbrood virus (SBV) and its application to a field survey of
      symptomatic honey bee colonies.
AB  - Sacbrood virus (SBV) is the causal agent of a disease of honey bee larvae,
      resulting in failure to pupate and causing death. The typical clinical symptom of
      SBV is an accumulation of SBV-rich fluid in swollen sub-cuticular pouches,
      forming the characteristic fluid-filled sac that gives its name to the disease.
      Outbreaks of the disease have been reported in different countries, affecting the
      development of the brood and causing losses in honey bee colonies. Today, few
      data are available on the SBV viral load in the case of overt disease in larvae,
      or for the behavioural changes of SBV-infected adult bees. A two-step real-time
      RT-PCR assay, based on TaqMan((r)) technology using a fluorescent probe (FAM
      TAMRA) was therefore developed to quantify Sacbrood virus in larvae, pupae and
      adult bees from symptomatic apiaries. This assay was first validated according to
      the recent XP-U47-600 standard issued by the French Standards Institute, where
      the reliability and the repeatability of the results and the performance of the
      assay were confirmed. The performance of the qPCR assay was validated over the 6
      log range of the standard curve (i.e. from 10(2) to 10(8) copies per well) with a
      measurement uncertainty evaluated at 0.11log10. The detection and quantitation
      limits were established respectively at 50 copies and 100 copies of SBV genome,
      for a template volume of 5MUl of cDNA. The RT-qPCR assay was applied during a
      French SBV outbreak in 2012 where larvae with typical SBV signs were collected,
      along with individuals without clinical signs. The SBV quantitation revealed
      that, in symptomatic larvae, the virus load was significantly higher than in
      samples without clinical signs. Combining quantitation with clinical data, a
      threshold of SBV viral load related to an overt disease was proposed (10(10) SBV
      genome copies per individual). 

PMID- 24121132
TI  - Interaction between cholecystokinin and the fibroblast growth factor system in
      the ventral tegmental area of selectively bred high- and low-responder rats.
AB  - Individual differences in the locomotor response to novelty have been linked to
      basal differences in dopaminergic neurotransmission. Mesolimbic dopaminergic
      outputs are regulated by cholecystokinin (CCK), a neuropeptide implicated in
      anxiety. In turn, CCK expression is regulated by fibroblast growth factor-2
      (FGF2), which has recently been identified as an endogenous regulator of anxiety.
      FGF2 binds to the high-affinity fibroblast growth factor receptor-1 (FGF-R1) to
      regulate the development and maintenance of dopamine neurons in the ventral
      tegmental area (VTA). However, the relationship between the FGF and CCK systems
      in the VTA is not well understood. Therefore, we utilized the selectively-bred
      low-responder (bLR; high-anxiety) and high-responder (bHR; low-anxiety) rats to
      examine the effects of repeated (21-day) FGF2 treatment on CCK and FGF-R1 mRNA in
      the rostral VTA (VTAr). In vehicle-treated controls, both CCK and FGF-R1 mRNA
      levels were increased in the VTAr of bLR rats relative to bHR rats. Following
      FGF2 treatment, however, bHR-bLR differences in CCK and FGF-R1 mRNA expression
      were eliminated, due to decreased CCK mRNA levels in the VTAr of bLR rats and
      increased FGF-R1 expression in bHR rats. Differences after FGF2 treatment may
      denote distinct interactions between the CCK and FGF systems in the VTAr of bHR
      vs. bLR rats. Indeed, significant correlations between CCK and FGF-R1 mRNA
      expression were found in bHR, but not bLR rats. Colocalization studies suggest
      that CCK and FGF-R1 are coexpressed in some VTAr neurons. Taken together, our
      findings suggest that the FGF system is poised to modulate both CCK and FGF-R1
      expression in the VTAr, which may be associated with individual differences in
      mesolimbic pathways associated with anxiety-like behavior. 

PMID- 24121134
TI  - Monoclonal antibody-based serological assays and immunocapture-RT-PCR for
      detecting Rice dwarf virus in field rice plants and leafhopper vectors.
AB  - Rice dwarf virus (RDV) causes Rice dwarf disease, which leads to considerable
      losses in rice production in Asia. Purified RDV virions were used as the
      immunogen to prepare monoclonal antibodies (mAbs). Three murine mAbs against RDV
      were prepared. Plate-trapped antigen enzyme-linked immunosorbent assay (PTA
      ELISA), dot enzyme-linked immunosorbent assay (dot-ELISA) and immunocapture-RT
      PCR (IC-RT-PCR) were then developed for sensitive, specific, and rapid detection
      of RDV in rice and leafhopper samples obtained in the field using the mAbs. The
      PTA-ELISA, dot-ELISA and IC-RT-PCR detected the virus in infected tissue crude
      extracts diluted at 1:81,920, 1:10,240 and 1:655,360 (w/v, g mL(-1)), in
      individual viruliferous rice green leafhopper crude extracts diluted at 1:25,600,
      1:6400 and 1:3,276,800 (individual leafhopper/MUL), respectively. 878 rice field
      samples and 531 leafhopper field samples from ten provinces of China were
      screened for the presence of RDV using the two serological assays and the IC-RT
      PCR and the results indicated that 37 of the 878 rice samples and 22 of the 531
      leafhopper samples were infected by RDV. All positive samples were from Yunnan
      Province, indicating that RDV is prevalent in this province, but not in the other
      nine provinces. The dot-ELISA is suitable for routine detection of large-scale
      rice and leafhopper samples in field surveys.

PMID- 24121135
TI  - Allele-specific qRT-PCR demonstrates superior detection of single nucleotide
      polymorphisms as genetic markers for West Nile virus compared to Luminex(r) and
      quantitative sequencing.
AB  - To enable in vivo and in vitro competitive fitness comparisons among West Nile
      viruses (WNV), three reference viruses were marked genetically by site-directed
      mutagenesis with five synonymous nucleotide substitutions in the envelope gene
      region of the genome. Phenotypic neutrality of the mutants was assessed
      experimentally by competitive replication in cell culture and genetic stability
      of the substituted nucleotides was confirmed by direct sequencing. Luminex((r))
      technology, quantitative sequencing and quantitative RT-PCR (qRT-PCR) were
      compared in regard to specificity, sensitivity and accuracy for quantitation of
      wildtype and genetically marked viruses in mixed samples based on RNA obtained
      from samples of known viral titers. Although Luminex((r)) technology and
      quantitative sequencing provided semi-quantitative or qualitative measurements, a
      sequence-specific primer extension approach using a specific reverse primer set
      in singleplex qRT-PCR demonstrated the best quantitation and specificity in the
      detection of RNA from wildtype and mutant viruses. 

PMID- 24121136
TI  - Production of monoclonal antibodies specific for the recombinant viral coat
      protein of Apple stem grooving virus-citrus isolate and their application for a
      simple, rapid diagnosis by an immunochromatographic assay.
AB  - A simple and rapid immunochromatographic assay (ICA) for the diagnosis of Apple
      stem grooving virus (ASGV) in citrus was developed. Nine lines of monoclonal
      antibodies (mAbs) were produced by immunizing with a recombinant viral coat
      protein of ASGV as the antigen. According to the competitive-binding ELISA
      results, the 9 mAbs comprised 2 paratope groups, A and B. After screening for the
      most effective combination of mAbs, the two lines from different paratope groups
      (4A12 from group A and 6N31 from group B) were used to create a colloidal gold
      conjugate and for the test line, respectively, in ICA test plate preparation. The
      ICA detection using this test plate was accurate for positive and negative
      samples, and ASGV was detectable to a dilution of 1:2430 for the infected citrus
      sample. Furthermore, ICA was more sensitive than ELISA for the detection of ASGV
      isolates in citrus. The simple and sensitive ICA for ASGV provides a
      straightforward method for diagnosis by non-experts, including nursery workers
      and growers. 

PMID- 24121137
TI  - Difference in amplitude of low-frequency fluctuation between currently depressed
      and remitted females with major depressive disorder.
AB  - Medical intervention for major depressive disorder (MDD) can be more
      appropriately focused through the identification and characterization of
      neurobiological markers that are specific to the disorder, and this study aims to
      examine the abnormality in the fractional amplitude of low-frequency fluctuation
      (fALFF) and the amplitude of low-frequency fluctuation (ALFF) in currently
      depressed and remitted female MDD patients and to correlate these fluctuations
      with clinical markers of MDD. Nineteen currently depressed female patients, 19
      remitted female patients, as well as 19 age- and education-matched healthy
      females participated in the resting-state functional magnetic resonance imaging
      (fMRI) analysis. We compared the fALFF/ALFF maps among the three groups and
      investigated the correlation between clinical measurements and statistically
      significant differences in the fALFF/ALFF of various brain regions. Compared with
      healthy controls, both currently depressed and remitted patients showed increased
      fALFF/ALFF in the right putamen. Currently depressed MDD patients showed
      increased fALFF/ALFF in the right ventral median frontal gyrus relative to both
      the remitted MDD group and the healthy control group. The ALFF of the right
      precuneus was found to be positively correlated with the number of depressive
      episodes and the fALFF of the right precuneus to be positively correlated with
      the disease duration in currently depressed MDD patients. An abnormal fALFF/ALFF
      in the right ventral median frontal gyrus was found only in currently depressed
      patients, suggesting that such an anomaly may play a critical role in depressive
      symptomatology and may be a therapeutic target for MDD. An abnormal fALFF/ALFF in
      the right putamen is a potential candidate as a trait-related marker of
      vulnerability to major depression. 

PMID- 24121139
TI  - Diffusive anisotropy in low-permeability Ordovician sedimentary rocks from the
      Michigan Basin in southwest Ontario.
AB  - Diffusive anisotropy was investigated using samples from Upper Ordovician shale
      and argillaceous limestone from the Michigan Basin of southwest Ontario, Canada.
      Effective diffusion coefficients (De) were determined for iodide (I(-)) and
      tritiated water (HTO) tracers on paired cm-scale subsamples oriented normal (NB)
      and parallel to bedding (PB) prepared from preserved drill cores within one year
      from the date of drilling. For samples with porosity >3%, an X-ray radiography
      method was used with I(-) tracer for determination of De and porosity accessible
      to I(-) ions. A through-diffusion method with I(-) and HTO tracers was used for
      most siltstone and limestone samples with low-porosity (<3%). The De values range
      from 7.0*10(-13) to 7.7*10(-12) m(2).s(-1) for shale, 2.1*10(-13) to 1.3*10(-12)
      m(2).s(-1) for limestone, and 5.3*10(-14) to 5.6*10(-13) m(2).s(-1) for siltstone
      and limestone interbeds within the Georgian Bay Formation shale. The sample-scale
      anisotropy ratios (De-PB:De-NB) for De values obtained using the I(-) tracer are
      0.9 to 4.9, and the anisotropy ratios for the HTO tracer are in the range of 1.1
      to 7.0. The influence of porosity distribution on diffusive anisotropy has been
      investigated using one-dimensional spatially-resolved profiles of I(-)-accessible
      porosity (shale only) and the use of AgNO3 for fixation of I(-) tracer in the
      pores, allowing for SEM visualization of I(-)-accessible pore networks. The
      porosity profiles at the sample scale display greatest variability in the
      direction normal to bedding which likely reflects sedimentary depositional
      processes. The SEM imaging suggests that diffusion pathways are preferentially
      oriented parallel to bedding in the shale and that diffusion occurs dominantly
      within the argillaceous component of the limestone. However, the fine clay-filled
      intergranular voids in the dolomitic domains of the limestone are also accessible
      for diffusive transport.

PMID- 24121138
TI  - Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea
      in Sprague-Dawley rat.
AB  - Obstructive sleep apnea represents a significant public health concern. Afferent
      vagal activation is implicated in increased apnea susceptibility by reducing
      upper airway muscle tone via activation of serotonin receptors in the nodose
      ganglia. Previous investigations demonstrated that systemically administered
      cannabinoids can be used therapeutically to decrease the apnea/hypopnea index in
      rats and in humans. However, cannabinoids have effects on both the central and
      peripheral nervous systems, and the exact mechanism of decreased apnea/hypopnea
      index with cannabinoids is unknown. Here, we hypothesized that intranodose
      ganglion injections of a cannabinoid will attenuate 5-HT-induced reflex apnea and
      increase upper airway muscle tone. We show that dronabinol injected locally into
      the nodose ganglia suppresses 5-HT-induced reflex apnea, and increases phasic,
      but not tonic, activation of the genioglossus. These data support the view that
      dronabinol stabilizes respiratory pattern and augments upper airway muscles by
      acting at the nodose ganglia. These findings underscore a therapeutic potential
      of dronabinol for the treatment of obstructive sleep apnea. 

PMID- 24121140
TI  - Hidradenitis suppurativa and pediatric Crohn disease.

PMID- 24121141
TI  - An innovative investigation into the etiology of feeding intolerance in preterm
      infants.

PMID- 24121142
TI  - Alternate endpoints and clinical outcome assessments in pediatric ulcerative
      colitis registration trials.
AB  - OBJECTIVES: Presently, there is no consensus on endpoint measures to assess
      clinical outcomes for pediatric ulcerative colitis (UC). This study reviewed the
      endpoints used in the registration trials of approved drugs for pediatric UC.
      METHODS: The primary efficacy endpoints of all registration trials completed from
      1950 to 2008 that led to Food and Drug Administration approval for indications in
      pediatric and adult UC were reviewed. RESULTS: Colazal and Remicade have been
      approved for pediatric UC indication, and clinical response was used as a primary
      endpoint in these registration trials. The clinical response in the adult Colazal
      trials was defined as a reduction of rectal bleeding and improvement in at least
      one of the other assessed symptoms (stool frequency, patient functional
      assessment, abdominal pain, sigmoidoscopic grade, and physician's global
      assessment) assessed by the Sutherland UC Activity Index. The pediatric Colazal
      trial defined clinical response using the Modified Sutherland UC Activity Index,
      which excluded abdominal pain and functional assessment. Both adult and pediatric
      Remicade trials used clinical response defined by the Mayo score as the primary
      endpoint. The Pediatric Ulcerative Colitis Activity Index was used to measure
      various secondary endpoints in the pediatric Remicade trial. CONCLUSIONS:
      Pediatric-specific endpoints were used, but outcome measures and definition of
      clinical response were not consistent in pediatric UC trials. Consensus on the
      definition of successful treatment outcome (clinical response and/or remission)
      and collaboration in the development of well-defined and reliable measures of
      signs and symptoms for use in conjunction with endoscopic parameters of mucosal
      healing will facilitate pediatric drug development.

PMID- 24121143
TI  - Lactobacillus reuteri ATCC55730 in cystic fibrosis.
AB  - OBJECTIVES: The aim of this study was to evaluate in patients with cystic
      fibrosis (CF) the effect of Lactobacillus reuteri (LR) on the rate of respiratory
      exacerbations and of the infections of both upper respiratory and
      gastrointestinal tracts. METHODS: Prospective randomized, double-blind, placebo
      controlled study enrolling 61 patients with CF with mild-to-moderate lung disease
      at the Regional Center for CF of the Department of Pediatrics, University of Rome
      "La Sapienza." All of the patients were not hospital inpatients at the time of
      the enrollment. Inclusion criteria were forced expiratory volume in the first
      second (FEV1) >70% predicted; no inhaled or systemic steroids, no anti
      inflammatory drugs, antileukotrienes, and mast cell membrane stabilizers; and no
      serious organ involvement. Exclusion criteria were a history of pulmonary
      exacerbation or upper respiratory infection in the previous 2 months; changes in
      medications in the last 2 months; a history of hemoptysis in the last 2 months;
      and colonization with Burkholderia cepacia or mycobacteria. Patients were
      randomly assigned to receive LR (30 patients) in 5 drops per day (10(10) colony
      forming units) or placebo (31 patients) for 6 months. Main outcomes were number
      of episodes of pulmonary exacerbations and hospital admissions for pulmonary
      exacerbations, number of gastrointestinal and upper respiratory tract infections.
      FEV1, fecal calprotectin, and cytokine profile in induced sputum and plasma were
      assessed at baseline and at the end of the trial. RESULTS: Pulmonary
      exacerbations were significantly reduced in the LR group compared with the
      placebo group (P<0.01; odds ratio 0.06 [95% confidence interval {CI} 0-0.40];
      number needed to treat 3 [95% CI 2-7]). Similarly, the number of upper
      respiratory tract infections (in our series only otitis) was significantly
      reduced in the LR group compared with the placebo group (P<0.05; odds ratio 0.14
      [95% CI 0-0.96]; number needed to treat 6 [95% CI 3-102]). The 2 groups did not
      differ statistically in the mean number and duration of hospitalizations for
      pulmonary exacerbations and gastrointestinal infections. There was no significant
      statistical difference in the mean delta value of FEV1, fecal calprotectin
      concentration, and tested cytokines (tumor necrosis factor-alpha and interleukin
      8) between the 2 groups. CONCLUSIONS: LR reduces pulmonary exacerbations and
      upper respiratory tract infections in patients with CF with mild-to-moderate lung
      disease. LR administration may have a beneficial effect on the disease course of
      CF.

PMID- 24121144
TI  - Gastrointestinal dysmotility in Rett syndrome.
AB  - OBJECTIVES: Through evidence review and the consensus of an expert panel, we
      developed recommendations for the clinical management of gastroesophageal reflux
      disease, constipation, and abdominal bloating in Rett syndrome. METHODS: Based on
      review of the literature and family concerns expressed on RettNet, initial draft
      recommendations were created. Wherein the literature was lacking, 25 open-ended
      questions were included. Input from an international, multidisciplinary panel of
      clinicians was sought using a 2-stage modified Delphi process to reach consensus
      agreement. Items related to the clinical assessment and management of
      gastroesophageal reflux disease, constipation, and abdominal bloating. RESULTS:
      Consensus was achieved on 78 of 85 statements. A comprehensive approach to the
      assessment of gastroesophageal reflux and reflux disease, constipation, and
      abdominal bloating was recommended, taking into account impairment of
      communication skills in Rett syndrome. A stepwise approach to the management was
      identified with initial use of conservative strategies, escalating to
      pharmacological measures and surgery, if necessary. CONCLUSIONS: Gastrointestinal
      dysmotility occurs commonly in Rett syndrome. These evidence- and consensus-based
      recommendations have the potential to improve care of dysmotility issues in a
      rare condition and stimulate research to improve the present limited evidence
      base.

PMID- 24121145
TI  - The next novelty in pediatric endoscopy: enteroscopy.

PMID- 24121146
TI  - Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants
      with symptomatic GERD.
AB  - AIM: : The efficacy and safety of rabeprazole, a proton pump inhibitor, were
      studied in infants with gastroesophageal reflux disease (GERD). METHODS: Infants
      ages 1 to 11 months, with symptomatic GERD resistant to conservative therapy
      and/or previous exposure to acid-suppressive medications, were screened. After
      scoring >16 on a GERD symptom score (Infant Gastroesophageal Reflux Questionnaire
      Revised [I-GERQ]), 344 infants were enrolled in a 1- to 3-week open-label (OL)
      phase and received rabeprazole 10 mg/day. Following caregiver-rated clinical
      improvement during the OL phase, patients were randomized to placebo, rabeprazole
      5 mg, or rabeprazole 10 mg in the ensuing 5-week double-blind (DB) withdrawal
      phase. Primary endpoints evaluated from DB baseline to the end of the DB
      withdrawal phase included frequency of regurgitation, weight-for-age z score, and
      daily and weekly GERD symptom scores. RESULTS: Overall, 231 (86%) of the 268
      randomized infants (placebo: 90; rabeprazole 5 mg: 90; rabeprazole 10 mg: 88)
      completed the study. Efficacy endpoints were similarly improved during the OL
      phase in all of the groups, and continued improving during the DB withdrawal
      phase with no difference between the placebo and combined rabeprazole groups.
      Mean decrease in frequency of regurgitation (-0.79 vs -1.20 times per day; P =
      0.168), in I-GERQ-Revised scores (-3.6 [-25%] vs -3.9 points [-27%]; P = 0.960),
      in I-GERQ-Daily Diary scores (-1.87 [-19%] vs -1.85 [-19%]; P = 0.968), and
      increase in weight-for-age z scores (mean [standard deviation]: 0.11 [0.329] vs
      0.14 [0.295]; P = 0.440) indicated equal improvement. Equal percentages (47%)
      reported adverse events in placebo and combined rabeprazole groups, with no new
      safety signals emerging. CONCLUSIONS: In those infants with GERD who improved
      with rabeprazole during the OL phase, improvements in symptoms and weight were
      similar in those who continued rabeprazole and those withdrawn to placebo during
      a 5-week DB phase.

PMID- 24121147
TI  - Appropriateness of newborn screening for alpha1-antitrypsin deficiency.
AB  - OBJECTIVE: The Alpha-1 Foundation convened a workshop to consider the
      appropriateness of newborn screening for alpha-1-antitrypsin (AAT) deficiency.
      METHODS: A review of natural history and technical data was conducted. RESULTS:
      Homozygous ZZ AAT deficiency is a common genetic disease occurring in 1 in 2000
      to 3500 births; however, it is underrecognized and most patients are undiagnosed.
      AAT deficiency can cause chronic liver disease, cirrhosis, and liver failure in
      children and adults, and lung disease in adults. The clinical course is highly
      variable. Some neonates present with cholestatic hepatitis and some children
      require liver transplantation, but many patients remain well into adulthood. Some
      adults develop emphysema. There is no treatment for AAT liver disease, other than
      supportive care and liver transplant. There are no data on the effect of early
      diagnosis on liver disease. Avoidance of smoking is of proven benefit to reduce
      future lung disease, as is protein replacement therapy. Justifying newborn
      screening with the aim of reducing smoking and reducing adult lung disease-years
      in the future would be a significant paradigm shift for the screening field.
      Recent passage of the Genetic Information Nondiscrimination Act (GINA) and the
      Affordable Care Act may have a major effect on reducing the psychosocial and
      financial risks of newborn screening because many asymptomatic children would be
      identified. Data on the risk-benefit ratio of screening in the new legal climate
      are lacking. CONCLUSIONS: Workshop participants recommended a series of pilot
      studies focused on generating new data on the risks and benefits of newborn
      screening.

PMID- 24121148
TI  - MRI-based score helps in assessing the severity and in follow-up of pediatric
      patients with perianal Crohn disease.
AB  - OBJECTIVES: The radiologic healing of perianal fistulizing Crohn disease (PfCD)
      lags behind the clinical healing. Contrast-enhanced pelvic magnetic resonance
      imaging (MRI) is the radiologic study of choice used to diagnose PfCD in
      children. The aim was to study whether the various MRI-based radiologic
      parameters and score can help in staging and follow-up of patients with PfCD.
      METHODS: We performed a retrospective chart review of children with PfCD who
      underwent contrast-enhanced MRI of the pelvis. The demographic profile, clinical
      status, and laboratory data of the patients at the time of each MRI examination
      were noted. Based on the clinical status of the patient at the time of MRI
      examinations, the MRIs were classified into 3 groups: severe disease, mild-to
      moderate disease, and asymptomatic. Each MRI examination was reviewed by a
      radiologist, who was blinded to the clinical status of the patient. RESULTS: Of
      the radiologic parameters, the number of fistulas, the complexity of fistulas,
      and the number of abscesses were significantly lower in the asymptomatic group
      compared with the mild-to-moderate and severe disease groups. The Van Assche MRI
      based score was significantly lower in the asymptomatic group compared with the
      mild-to-moderate disease (P = 0.01) and the severe disease group (P = 0.002). The
      percentage increase in fistula activity after gadolinium administration was
      significantly lower in the asymptomatic group compared with the mild-to-moderate
      disease (P = 0.026) and severe disease (P = 0.019) groups. The MRI-based scores
      were significantly higher in the MRI examinations performed at diagnosis compared
      with those that were performed while the patients were receiving the treatment (P
      = 0.017). CONCLUSIONS: The Van Assche MRI score and the percentage increase in
      fistula activity after gadolinium administration help in assessing the severity
      perianal Crohn disease. The Van Assche MRI score may be helpful in documenting
      healing during therapy of perianal Crohn disease.

PMID- 24121150
TI  - Role of Treg and TH17 cells of the gastric mucosa in children with Helicobacter
      pylori gastritis.
AB  - OBJECTIVE: The aim of the present study was to examine the expression of FOXP3,
      interleukin (IL)-10, transforming growth factor (TGF)-beta1, IL-17A, and T helper
      17 (TH17) cells/FOXP3+ regulatory T (Treg) cells balance in the gastric mucosa of
      children with Helicobacter pylori infection, in relation to the gastric
      histopathology. METHODS: Antral mucosal biopsies were obtained from 20 children
      with H pylori(+) gastritis and 20 age- and sex-matched normal controls.
      Histopathology was assessed by the updated Sydney classification. Gene expression
      of FOXP3, IL-10, and TGF-beta1 was analyzed by quantitative real-time polymerase
      chain reaction. Immunohistochemical staining for FOXP3+ Treg and TH17 cells was
      performed. RESULTS: The gene expression levels of FOXP3, TGF-beta1, and IL-10
      messenger RNA (mRNA) and the number of FOXP3+ Treg were significantly higher in
      the H pylori(+) gastritis group than in the control group (P < 0.01). FOXP3 mRNA
      levels were correlated positively with TGF-beta1 and IL-10 mRNA levels in the H
      pylori(+) gastritis group (P < 0.05). Furthermore, FOXP3 mRNA levels were
      correlated positively with the bacterial density, infiltration of
      polymorphonuclear cells, and mononuclear cells in the H pylori(+) gastritis group
      (P < 0.05). The number of TH17 cells was significantly higher in the H pylori(+)
      gastritis group than in the control group (P < 0.05). In addition, the number of
      TH17 cells was correlated negatively with the bacterial density and positively
      with the inflammatory scores of polymorphonuclear cells and mononuclear cells in
      the H pylori(+) gastritis group (P < 0.05). A negative correlation between the
      TH17 cells/FOXP3+ Treg ratio and the bacterial density was demonstrated in the H
      pylori(+) gastritis group (P < 0.05). CONCLUSIONS: This study suggested that a
      TH17/Treg balance toward a Treg-biased response favors the persistence of
      bacteria, causing chronic active gastritis.

PMID- 24121149
TI  - Enteral zinc supplementation and growth in extremely-low-birth-weight infants
      with chronic lung disease.
AB  - OBJECTIVE: Zinc deficiency causes growth deficits. Extremely-low-birth-weight
      (ELBW) infants with chronic lung disease (CLD), also known as bronchopulmonary
      dysplasia, experience growth failure and are at risk for zinc deficiency. We
      hypothesized that enteral zinc supplementation would increase weight gain and
      linear growth. METHODS: A cohort of infants was examined retrospectively at a
      single center between January 2008 and December 2011. CLD was defined as the need
      for oxygen at 36 weeks postmenstrual age. Zinc supplementation was started in
      infants who had poor weight gain. Infants' weight gain and linear growth were
      compared before and after zinc supplementation using the paired t test. RESULTS:
      A total of 52 ELBW infants with CLD met entry criteria. Mean birth weight was 682
      +/- 183 g, and gestational age was 25.3 +/- 2 weeks. Zinc supplementation started
      at postmenstrual age 33 +/- 2 weeks. Most infants received fortified human milk.
      Weight gain increased from 10.9 before supplementation to 19.9 g . kg(-1) . day(
      1) after supplementation (P < 0.0001). Linear growth increased from 0.7 to 1.1
      cm/week (P = 0.001). CONCLUSIONS: Zinc supplementation improved growth in ELBW
      infants with CLD receiving human milk. Further investigation is warranted to
      reevaluate zinc requirements, markers, and balance.

PMID- 24121151
TI  - Effect of propofol on anal sphincter pressure during anorectal manometry.
AB  - We evaluated the effect of propofol on resting anal sphincter pressure (RP)
      during anorectal manometry performed under general anesthesia in 20 children with
      chronic constipation. After propofol bolus administration, there was a
      significant decrease in the RP in 95% of children from a mean of 51.5 +/- 15.3 to
      a mean nadir of 21.7 +/- 10.5 mmHg (P < 0.001). The new postpropofol RP of 47.0
      +/- 12.4 mmHg was significantly lower compared with prepropofol RP (P < 0.0001).
      Propofol should be used with caution as an anesthetic agent for anorectal
      manometry, given the potential for confounding RP measurements.

PMID- 24121152
TI  - Combined restitutive therapy for treatment of immunosuppressive refractory Crohn
      disease.

PMID- 24121153
TI  - Tracking suicide risk factors through Twitter in the US.
AB  - BACKGROUND: Suicide is a leading cause of death in the United States. Social
      media such as Twitter is an emerging surveillance tool that may assist
      researchers in tracking suicide risk factors in real time. AIMS: To identify
      suicide-related risk factors through Twitter conversations by matching on
      geographic suicide rates from vital statistics data. METHOD: At-risk tweets were
      filtered from the Twitter stream using keywords and phrases created from suicide
      risk factors. Tweets were grouped by state and departures from expectation were
      calculated. The values for suicide tweeters were compared against national data
      of actual suicide rates from the Centers for Disease Control and Prevention.
      RESULTS: A total of 1,659,274 tweets were analyzed over a 3-month period with
      37,717 identified as at-risk for suicide. Midwestern and western states had a
      higher proportion of suicide-related tweeters than expected, while the reverse
      was true for southern and eastern states. A strong correlation was observed
      between state Twitter-derived data and actual state age-adjusted suicide data.
      CONCLUSION: Twitter may be a viable tool for real-time monitoring of suicide risk
      factors on a large scale. This study demonstrates that individuals who are at
      risk for suicide may be detected through social media.

PMID- 24121154
TI  - Oxidative stress is involved in fatigue induced by overnight deskwork as assessed
      by increase in plasma tocopherylhydroqinone and hydroxycholesterol.
AB  - In this study, we examined the relationship between fatigue and plasma
      concentrations of antioxidants and lipid peroxidation products. Fourteen healthy
      volunteers performed overnight desk work for 18h then took a nap for 4h.
      Participants answered questionnaires of subjective symptoms of fatigue (QSSF) and
      completed a self-assessment of fatigue using a visual analog scale (VAS). At each
      test time, they underwent a critical flicker frequency (CFF) test and blood
      samples were collected. Plasma levels of alpha-tocopherol (alphaT) decreased and
      alpha-tocopherylquinone (alphaTQ), the oxidation product of alphaT, increased.
      The ratio of 7beta-hydroxycholesterol (7beta-OHCh), the oxidation product of
      cholesterol, against total cholesterol increased until the end of experiment.
      alphaTQ levels correlated with VAS and QSSF scores. The ratio of 7beta-OHCh to
      total cholesterol and the value of CFF showed a significant correlation. From
      these results, plasma levels of alphaTQ and 7beta-OHCh are useful and objective
      indicators of fatigue induced by overnight deskwork. 

PMID- 24121155
TI  - Shyness and emotional face processing in schizophrenia: an ERP study.
AB  - Shyness in healthy controls has been related to early event-related potential
      (ERP) responses to emotional faces. Patients with schizophrenia typically
      demonstrate increased shyness that is stable and related to reduced social
      functioning. We indexed early ERP responses to emotional faces in relation to
      shyness in 40 outpatients with schizophrenia and 39 healthy controls. Patients
      with low-to-medium shyness showed reductions in P100 amplitude to emotional
      compared to neutral faces as shyness increased. Patients reporting medium-to-high
      shyness demonstrated the opposite pattern; P100 amplitude sharply increased as
      shyness increased, possibly reflecting heightened vigilance. When a restricted
      range of shyness scores was used to equalize scores between groups, patients
      showed increased N170 amplitude to emotional faces as shyness increased, whereas
      controls demonstrated the opposite pattern. The implications of the findings are
      discussed with respect to informing vulnerability to social functioning
      impairment and psychosocial stress in this population. 

PMID- 24121156
TI  - Label-free DNAsensor with PCR-like sensitivity based on background reduction and
      target-triggered polymerization amplification.
AB  - In this work, we have developed a highly sensitive and label-free DNAsensor for
      nucleic acid detection based on background noise reduction by exonuclease I (Exo
      I) and target-triggered cycled polymerization amplification. This DNAsensor
      consists of a long-tail probe, a short primer and polymerase. In the absence of
      the target, the long-tail probe and short primer are digested by Exo I, which
      minimizes the intercalation of fluorescence dye and reduces the background noise.
      In the presence of the target, the specific binding between the long-tail probe
      and the target triggers cycled polymerization reactions to form long dsDNA
      products. These long dsDNA products prevent effectively them from degrading by
      Exo I and amplify the fluorescence signals. In our sensing approach, the
      combination of the ExoI-assisted background reduction with the cycled
      polymerization amplification allows us to achieve a PCR-like sensitivity without
      labeling, washing separation and temperature cycles in a homogenous solution.
      Using total RNA samples extracted from hepatitis C virus (HCV) as targets, we
      further demonstrate the detection capability of the DNAsensor for complex nucleic
      acid samples, indicating its potential applicability for clinic molecular
      diagnostic assays. 

PMID- 24121157
TI  - Construction of highly ordered polyaniline nanowires and their applications in
      DNA sensing.
AB  - A novel electrochemical active polyaniline (PANI) nanowire was fabricated and
      utilized for the construction of a highly sensitive and selective electrochemical
      sensor for hepatitis B virus gene. The uniform PANI nanowire was prepared by the
      enzymatic polymerization of aniline monomers on the amyloid-like nanofiber (AP
      nanowire), which was self-assembled from an aniline-attached nonapeptide, aniline
      GGAAKLVFF (AP). The prepared PANI nanowires were characterized by electron
      microscopy, UV-vis absorption spectra, and cyclic voltammetry (CV). These ultra
      thin nanowires displayed high electrochemical activity. Then the nucleic acid
      biosensor was constructed by modifying a glass carbon electrode with AP nanowires
      which were functionalized by a designed hair-pin loop DNA. Upon the presence of
      target nucleic acid and horseradish peroxidase (HRP) labeled oligonucleotide, the
      HRP will catalyze the polymerization of aniline monomers conjugated in AP
      nanowires, leading to the formation of PANI nanowires which can bring about a
      dramatical increase in the current response of the biosensor. The dynamic range
      of the sensor for hepatitis B virus gene is 2.0-800.0 fM with a low detection
      limit of 1.0 fM (3sigma, n=10). The biosensor also displayed highly selectivity
      and stability. All these excellent performances of the developed biosensor
      indicate that this platform can be easily extended to the detection of other
      nucleic acids.

PMID- 24121158
TI  - Allelopathic effects of microcystin-LR on the germination, growth and metabolism
      of five charophyte species and a submerged angiosperm.
AB  - Microcystins (MCs) are produced by cyanobacteria in aquatic environments and
      adversely affect macrophytes at very high concentrations. However, the effects of
      MC on macrophytes at concentrations of environmental relevance are largely
      unknown. The main objective of this study was to analyze the allelopathic effects
      of MC-LR at natural concentrations (1, 8 and 16 MUg MC-LR/L) on five charophyte
      species (Chara aspera, C. baltica, C. hispida, C. vulgaris and Nitella hyalina)
      and the angiosperm Myriophyllum spicatum. Macrophyte specimens were obtained from
      a restored area located in Albufera de Valencia Natural Park, a protected coastal
      Mediterranean wetland. Two different experiments were conducted involving (i) the
      addition of MC-LR to natural sediment to evaluate its effects on seed germination
      and (ii) the addition of MC-LR to water cultures of macrophytes to evaluate its
      effects on growth and metabolic functions. In water, the MC-LR concentration
      decreased by 84% in two weeks; the loss was not significant in sediment. The
      first seedlings (all C. hispida) emerged from the wetland sediment following a
      delay of a few days in the presence of MC-LR. The germination rates in 8 and 16
      MUg MC-LR/L treatments were 44% and 11% of that occurring in the absence of MC,
      but these differences disappeared over time. The final density was 6-7
      germlings/dm(3). Final germling length was unaffected by MC-LR. Rotifers (Lecane
      spp.) emerging from the natural sediment during the experiment were favored by MC
      LR; the opposite pattern was observed in the cladoceran Daphnia magna. The growth
      rates of C. vulgaris, C. baltica and N. hyalina were unaffected by MC exposure,
      whereas those of C. hispida and C. aspera were reduced in the MC treatments
      relative to the control treatment. The concentration of chlorophyll-a and the in
      vivo net photosynthetic rate were lower in the presence of MC-LR, even at the
      lowest concentration, for all of the characeans tested. M. spicatum was sensitive
      to the presence of MC-LR in the culture medium; the growth and chlorophyll-a
      concentrations were reduced. Therefore, environmentally relevant concentrations
      of MC might induce important changes in macrophyte meadows and the structure of
      the associated plankton community. Synchrony or delay in the processes evaluated
      here in response to environmentally relevant concentrations of cyanobacteria MC
      exudates can enhance understanding of the turning point to alternative states and
      the point of no return in eutrophicated shallow lakes.

PMID- 24121159
TI  - PCB-153 and temperature cause restructuring of goldfish membranes: homeoviscous
      response to a chemical fluidiser.
AB  - Ortho-substituted PCBs intercalate between membrane phospholipids similarly to
      cholesterol and increase fluidity. Ectothermic animals have a well-developed
      homeoviscous response to counter the fluidising effect of temperature and avoid
      the disruption of membrane proteins. However, it remains unknown whether chemical
      fluidisation can also activate a homeoviscous response or interfere with normal
      acclimation to temperature. The fatty acid composition and cholesterol content of
      membranes from gill, white muscle, liver, and brain was measured in goldfish
      exposed to 4 treatments in a 2 * 2 factorial design (acclimated to 5 or 20
      degrees C, and exposed or not to PCB-153). The expression of Delta6 and Delta9
      desaturases was also measured in gill and liver because these enzymes modulate
      changes in membrane unsaturation. We hypothesised that thermal and chemical
      stress would cause similar adjustments in phospholipid unsaturation, membrane
      cholesterol, and desaturase expression. Results show that PCB-153 triggers a
      homeoviscous response by changing cholesterol content in liver (+51%) and brain
      (+216%), as well as the double bond index in gills (-17%). In response to higher
      temperature, the membranes of gill, muscle, and brain substitute polyunsaturated
      fatty acids such as arachidonate [20:4] and eicosadienoate [20:2] with saturated
      fatty acids such as palmitate [16:0] and stearate [18:0]. Each tissue has a
      distinct pattern of changes, suggesting that different local factors contribute
      to the stress response. It is also possible that the thermal tolerance of
      individual species influences the homeoviscous response because the changes
      observed in goldfish liver are not consistent with what has been reported for
      trout liver. No evidence supporting the activation of desaturase expression could
      be found. Overall, and contrary to expectation, modulating membrane cholesterol
      is the main mechanism used to cope with PCB-153, whereas changes in unsaturation
      dominate temperature acclimation. If also present in other species, these
      protective responses may prove particularly important for polar fish that face
      the combined effects of thermal stress from climate change and chemical stress
      from organochlorine deposition. This study is the first to show that in vivo
      exposure to a membrane fluidiser can cause a homeoviscous response in an
      ectothermic animal. We conclude that the homeostatic mechanisms that preserve
      normal membrane function vary: (1) with the nature of the stress that perturbs
      fluidity, (2) with local conditions within each tissue, and (3) possibly with the
      thermal tolerance of individual species. These complicating factors will have to
      be considered in future studies of homeoviscous adjustments.

PMID- 24121161
TI  - Microorganisms and typical organic matter responsible for lacustrine "black
      bloom".
AB  - Identifying the causation of the black substance in lacustrine "black bloom" is
      of great significance for forecasting and preventing black bloom in many waters
      of the world. In this research, an array of black bloom was simulated in a
      laboratory to investigate how microorganisms and organic matter affect black
      bloom. Sulphate-reducing bacteria (SRB) are the main biological factor, and
      protein is the key organic factor contributing to lacustrine black bloom. The
      black colour of black bloom is strongly associated with a relatively high SRB
      population density. Hydrogen sulphide concentration can serve as a predictor of
      black bloom. 

PMID- 24121160
TI  - Crystal nucleation and near-epitaxial growth in nacre.
AB  - Nacre is the iridescent inner lining of many mollusk shells, with a unique
      lamellar structure at the sub-micron scale, and remarkable resistance to
      fracture. Despite extensive studies, nacre formation mechanisms remain
      incompletely understood. Here we present 20-nm, 2 degrees -resolution
      polarization-dependent imaging contrast (PIC) images of shells from 15 mollusk
      species, mapping nacre tablets and their orientation patterns. These data show
      where new crystal orientations appear and how similar orientations propagate as
      nacre grows. In all shells we found stacks of co-oriented aragonite (CaCO3)
      tablets arranged into vertical columns or staggered diagonally. Near the nacre
      prismatic (NP) boundary highly disordered spherulitic aragonite is nucleated.
      Overgrowing nacre tablet crystals are most frequently co-oriented with the
      underlying aragonite spherulites, or with another tablet. Away from the NP
      boundary all tablets are nearly co-oriented in all species, with crystal lattice
      tilting, abrupt or gradual, always observed and always small (plus or minus 10
      degrees ). Therefore aragonite crystal growth in nacre is near-epitaxial. Based
      on these data, we propose that there is one mineral bridge per tablet, and that
      "bridge tilting" may occur without fracturing the bridge, hence providing the
      seed from which the next tablet grows near-epitaxially.

PMID- 24121162
TI  - N-alkanes and polycyclic aromatic hydrocarbons in total suspended particulates
      from the southeastern Tibetan Plateau: concentrations, seasonal variations, and
      sources.
AB  - Sixty-two suspended particle (TSP) samples were collected from Lulang on the
      southeastern Tibetan Plateau from July 2008 and July 2009 to investigate the
      concentrations, seasonal variations, and sources of n-alkanes and polycyclic
      aromatic hydrocarbons (PAHs). Samples were analyzed using thermal-deposition gas
      chromatography mass spectrometry. The concentrations of particulate total n
      alkanes ranged from 0.10 to 21.83 ng m(-3), with an annual mean of 1.25 ng m(-3);
      the PAHs ranged from 0.06 to 2.53, with a mean of 0.59 ng m(-3). Up to 70% of
      PAHs were 5- and 6-ring compounds. The n-alkanes and PAHs both showed higher
      concentrations in winter and lower concentrations in summer. Analyses of
      diagnostic ratios indicate that 6.4% to 58.9% (mean 24.9%) of the n-alkanes were
      from plant waxes. Source characterization studies, i.e. diagnostic ratio and
      positive factor matrix analysis, suggest that the PAHs were from biomass burning
      as well as from fossil fuel combustion. Backward trajectory analysis suggests
      that the biomass mass burning pollutants could be from South Asia and western
      China via long distance transport. The study contributes to a more comprehensive
      understanding of the concentrations, seasonal variations, and sources of n
      alkanes and PAHs in a remote background area in Tibetan Plateau.

PMID- 24121163
TI  - The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and
      implications for leukaemia using three different genome-wide screening methods.
AB  - The reciprocal translocation t(12;21)(p13;q22), the most common structural
      genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children,
      results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified
      directly and indirectly regulated target genes utilizing an inducible TEL-AML1
      system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody
      directed against TEL-AML1. By integration of promoter binding identified with
      chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output
      through microarray technology and stable labelling of amino acids in cell
      culture, we identified 217 directly and 118 indirectly regulated targets of the
      TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were
      enriched in AML1-binding sites. The majority of promoter regions were specific
      for the fusion protein and not bound by native AML1 or TEL. Comparison with gene
      expression profiles from TEL-AML1-positive patients identified 56 concordantly
      misregulated genes with negative effects on proliferation and cellular transport
      mechanisms and positive effects on cellular migration, and stress responses
      including immunological responses. In summary, this work for the first time gives
      a comprehensive insight into how TEL-AML1 expression may directly and indirectly
      contribute to alter cells to become prone for leukemic transformation. 

PMID- 24121165
TI  - Ten years EULAR Scleroderma Research and Trials (EUSTAR): what has been achieved?
AB  - Ten years ago a group of researchers interested in and dedicated to the field of
      systemic sclerosis started a unique experiment called European League Against
      Rheumatism (EULAR) Scleroderma Trials And Research (EUSTAR) that was designed to
      establish a large-scale database in a rare disease to facilitate the exact
      characterisation of this debilitating disease, spread the knowledge even beyond
      the borders of Europe and stimulate innovative research targeting the major
      problems of the affected patients. This EUSTAR experiment, with all its facets,
      including the creation of a large-scale database, the initiation of more than 40
      investigator-driven clinical and basic science projects, the teaching of more
      than 400 young clinicians in the field of systemic sclerosis and the realisation
      of multicenter EU grants, which were all facilitated by an initial research grant
      from EULAR, is outlined and commented upon by the members of the steering
      committee in this viewpoint article on behalf of the now more than 150
      contributing centres and the international systemic sclerosis patients'
      association, the Federation of European Scleroderma Associations. 

PMID- 24121164
TI  - Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B
      cell lymphoma.
AB  - Deregulation of microRNA (miRNA) expression has been documented in diffuse large
      B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in
      DLBCL is not fully determined. Here, we assessed the role of miRNA expression and
      their processing genes in DLBCL development. Using microarray and RT-qPCR
      approaches, we quantified global miRNAs and core components of miRNA-processing
      genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes
      (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or
      between the de novo and transformed DLBCLs. We also identified subsets of miRNAs
      associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and
      clinical staging. In addition, we showed a significant over-expression of TARBP2
      in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA,
      DICER, TARBP2 and PACT in transformed as compared with de novo cases.
      Interestingly, cases with high TARBP2 and DROSHA expression had a poorer
      chemotherapy response. We further showed that TARBP2 can regulate miRNA
      processing efficiency in DLBCLs, and its expression inhibition decreases cell
      growth and increases apoptosis in DLBCL cell lines. Our findings provide new
      insights for the understanding of miRNAs and its machinery in DLBCL. 

PMID- 24121166
TI  - Pronociception from the dorsomedial nucleus of the hypothalamus is mediated by
      the rostral ventromedial medulla in healthy controls but is absent in arthritic
      animals.
AB  - The dorsomedial nucleus of the hypothalamus (DMH) has been proposed to
      participate in stress-induced hyperalgesia through facilitation of pronociceptive
      cells in the rostroventromedial medulla (RVM). We hypothesized that the DMH
      participates in hyperalgesia induced by arthritis. The DMH was pharmacologically
      manipulated while assessing heat-evoked nociceptive behavior or the discharge
      rates of pronociceptive RVM ON- and antinociceptive RVM OFF-like cells in NAIVE,
      SHAM and monoarthritic (ARTH) animals. In NAIVE and SHAM animals, the changes in
      nociceptive behavior induced by activation of the DMH by glutamate and inhibition
      by lidocaine were in line with earlier evidence indicating that the DMH has a
      nociceptive facilitating role. However, in ARTH animals, neither activation nor
      inhibition of the DMH influenced pain-like behavior evoked by stimulation of an
      uninflamed skin region (paw and tail). In accordance with these behavioral
      results, activation or inhibition of the DMH induced pronociceptive changes in
      the discharge rates of RVM cells in NAIVE and SHAM animals, which suggests that
      the DMH has a pronociceptive role mediated by the RVM in normal animals. However,
      in ARTH animals, both glutamate and lidocaine in the DMH failed to influence
      either pain-like behavior or noxious stimulation-evoked responses of RVM cells,
      while blocking the DMH increased spontaneous activity in the pronociceptive RVM
      ON cells. Our data indicate that the DMH participates in descending facilitation
      of cutaneous nociception in healthy controls, but it is not engaged in the
      regulation of cutaneous nociception in monoarthritic animals, while a minor role
      in tonic suppression of nociception in arthritis cannot be discarded. 

PMID- 24121167
TI  - Gene trapping using gal4 in zebrafish.
AB  - Large clutch size and external development of optically transparent embryos make
      zebrafish an exceptional vertebrate model system for in vivo insertional
      mutagenesis using fluorescent reporters to tag expression of mutated genes.
      Several laboratories have constructed and tested enhancer- and gene-trap vectors
      in zebrafish, using fluorescent proteins, Gal4- and lexA- based transcriptional
      activators as reporters (1-7). These vectors had two potential drawbacks:
      suboptimal stringency (e.g. lack of ability to differentiate between enhancer-
      and gene-trap events) and low mutagenicity (e.g. integrations into genes rarely
      produced null alleles). Gene Breaking Transposon (GBTs) were developed to address
      these drawbacks (8-10). We have modified one of the first GBT vectors, GBT-R15,
      for use with Gal4-VP16 as the primary gene trap reporter and added UAS:eGFP as
      the secondary reporter for direct detection of gene trap events. Application of
      Gal4-VP16 as the primary gene trap reporter provides two main advantages. First,
      it increases sensitivity for genes expressed at low expression levels. Second, it
      enables researchers to use gene trap lines as Gal4 drivers to direct expression
      of other transgenes in very specific tissues. This is especially pertinent for
      genes with non-essential or redundant functions, where gene trap integration may
      not result in overt phenotypes. The disadvantage of using Gal4-VP16 as the
      primary gene trap reporter is that genes coding for proteins with N-terminal
      signal sequences are not amenable to trapping, as the resulting Gal4-VP16 fusion
      proteins are unlikely to be able to enter the nucleus and activate transcription.
      Importantly, the use of Gal4-VP16 does not pre-select for nuclear proteins: we
      recovered gene trap mutations in genes encoding proteins which function in the
      nucleus, the cytoplasm and the plasma membrane. 

PMID- 24121168
TI  - The helmet head restraint system: a viable solution for resting state fMRI in
      awake monkeys.
AB  - In monkey neuroimaging, head restraint is currently achieved via surgical
      implants. Eradicating such invasive head restraint from otherwise non-invasive
      monkey studies could represent a substantial progress in terms of Reduction and
      Refinement. Two non-invasive helmet-based methods are available but they are used
      exclusively by the pioneering research groups who designed them. In the absence
      of independent replication, they have had little impact in replacing the surgical
      implants. Here, we built a modified version of the helmet system proposed by
      Srihasam et al. (2010 NeuroImage, 51(1), 267-73) and tested it for resting state
      fMRI in awake monkeys. Extremely vulnerable to motion artifacts, resting state
      fMRI represents a decisive test for non-invasive head restraint systems. We
      compared two monkeys restrained with the helmet to one monkey with a surgically
      implanted head post using both a seed-based approach and an independent component
      analysis. Technically, the helmet system proved relatively easy to develop.
      Scientifically, although it allowed more extensive movements than the head post
      system, the helmet proved viable for resting state fMRI, in particular when
      combined with the independent component analysis that deals more effectively with
      movement-related noise than the seed-based approach. We also discuss the pros and
      cons of such device in light of the European Union new 2013 regulation on non
      human primate research and its firm Reduction and Refinement requests. 

PMID- 24121169
TI  - Endometrioid stromal sarcoma: a clinicopathologic study of 63 cases.
AB  - Endometrioid stromal sarcoma (also known as extrauterine endometrial stromal
      sarcoma [EESS]) is an uncommon tumor that occurs in women over a wide age range.
      The extrauterine location, non-gynecologic symptoms and signs at presentation,
      and confounding histologic features can pose a diagnostic challenge. In this
      study, we present the clinicopathologic features of 63 cases of EESS seen during
      a period of 21 years at our institution. Clinical information and pathology
      material were reviewed. Ages ranged from 27 to 87 years (median: 50 years). The
      most common symptoms and signs were an abdominal or pelvic mass, pain, vaginal
      bleeding, and gastrointestinal symptoms. The tumor size ranged from 1.2 to 24.5
      cm. The most common sites of involvement were the ovaries (25), bowel wall (28),
      abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites were
      involved in 40 cases. Forty-six of 49 tumors had a classic microscopic
      appearance, and 3 had dedifferentiation; in 20 cases, there was vascular
      invasion. Fibroma-like stroma was seen in 30, hyaline plaques in 23, sex cord
      elements in 11, smooth muscle differentiation in 4, and myxoid change in 4 cases.
      Endometriosis was noted in 30 cases. Immunohistochemical results included: CD10
      positivity in 31, desmin positivity in 9 (focal), estrogen receptor positivity in
      28, and progesterone receptor positivity in 33 cases. In 25% of cases, an initial
      diagnosis other than EESS was made: sex cord-stromal tumors (4), gastrointestinal
      stromal tumor (3), leiomyosarcoma (3), liposarcoma (1), mullerian adenosarcoma
      (1), synovial sarcoma (1), malignant peripheral nerve sheath tumor (1), small
      round blue cell tumor (1), and atypical stromal endometriosis (1). Primary
      treatment was cytoreductive surgery for 61 patients and hormonal therapy for 2
      patients. Adjuvant treatment included hormonal therapy, chemotherapy, and
      radiation therapy. Follow-up (5 to 336 months) information was available for 53
      patients: alive with no evidence of disease, 29; alive with disease, 15; and dead
      of disease, 9 (median period of 70 months from diagnosis to death). Thirty-three
      patients had recurrent disease, and 10 patients were lost to follow-up. EESS is
      commonly associated with endometriosis and tends to be indolent with a propensity
      for recurrence. Seven of 9 patients who died of the disease had bowel
      involvement, and 3 had tumors with dedifferentiation. Besides the latter, no
      other histologic finding correlated with the clinical behavior of these tumors.

PMID- 24121170
TI  - Grading of well-differentiated pancreatic neuroendocrine tumors is improved by
      the inclusion of both Ki67 proliferative index and mitotic rate.
AB  - The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010
      by the World Health Organization (WHO) mandates the use of both mitotic rate and
      Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In
      cases when these measures are not concordant for grade, it is recommended to
      assign the higher grade, but specific data justifying this approach do not exist.
      Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297
      WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We
      quantified the Ki67 proliferative index by marking at least 500 cells in "hot
      spots" and by using digital image analysis software to count each marked
      positive/negative cell and then compared the results with histologic features and
      overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by
      Ki67 proliferative index. Compared with concordant grade 1 tumors, grade
      discordant tumors were more likely to have metastases to lymph node (56% vs. 34%)
      (P<0.01) and to distant sites (46% vs. 12%) (P<0.01). Discordant mitotic grade 1
      PanNETs also showed statistically significantly more infiltrative growth
      patterns, perineural invasion, and small vessel invasion. Overall survival was
      significantly different (P<0.01), with discordant mitotic grade 1 tumors showing
      a median survival of 12 years compared with 16.7 years for concordant grade 1
      tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant
      differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2.
      Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often
      discordant, and when the Ki67 grade is greater than the mitotic grade, clinical
      outcomes and histopathologic features are significantly worse than concordant
      grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have
      shorter overall survival and larger tumors with more metastases and more
      aggressive histologic features. These data strongly suggest that Ki67 labeling be
      performed on all PanNETs in addition to mitotic rate determination to define more
      accurately tumor grade and prognosis.

PMID- 24121171
TI  - Respiratory epithelial adenomatoid hamartoma: a poorly recognized entity with
      mast cell recruitment and frequently associated with nasal polyposis.
AB  - Respiratory epithelial adenomatoid hamartoma (REAH) is regarded as a rare tumor
      of the nasal cavity. The mechanisms driving the development of REAH are unknown,
      and its nature as a benign tumor, hamartoma, or reactive inflammatory process is
      still open to discussion. A total of 150 consecutive patients operated on for
      nasal polyposis (NP) were extensively checked for the diagnosis of REAH. The
      profile of REAH occurring in association with NP was compared with solitary REAH
      in a series of 19 cases. The possible role of tryptase-producing mast cells (MC)
      and of metalloproteinases MMP2 and MMP9 in REAH development was investigated by
      immunohistochemistry. REAH lesions were identified in 35% of patients who had
      surgery for NP (53/150). The distribution of the lesions suggested that REAH
      originated in the olfactory cleft. Solitary REAH occurred about 20 times less
      frequently than those observed in an NP context but shared the same microscopic
      characteristics. Tryptase-producing MCs were recruited at high density in REAH
      (135/10 hpf), compared with inflammatory polyps (45/10 hpf; P<0.00005) and
      hypertrophied turbinates (51/10 hpf; P<0.0005). REAH also showed constant MMP9
      expression and to a lesser degree MMP2 expression in epithelial cells. If
      solitary REAH is a relatively rare lesion, we demonstrated that an exhaustive
      sampling allows the detection of a high proportion of NP-associated REAH, sharing
      the same clinical and histologic characteristics with solitary REAH. Tryptase
      producing MCs, possibly in association with MMP expression, may play a central
      role in REAH formation.

PMID- 24121172
TI  - Endobronchial lipomatous tumors: clinicopathologic analysis of 12 cases with
      molecular cytogenetic evidence supporting classification as "lipoma".
AB  - Lipomatous lesions rarely involve the bronchial tree, and detailed morphologic
      and molecular cytogenetic analysis of these tumors is lacking. The
      clinicopathologic features of 12 endobronchial lipomatous neoplasms were studied,
      with ancillary fluorescence in situ hybridization performed in subsets of cases
      for CPM, which is amplified in atypical lipomatous tumors/well-differentiated
      liposarcomas (ALT/WDL), and HMGA1 and HMGA2, which are often rearranged in
      lipomas. The cases occurred predominately in older men (91%) (age range 44 to 80
      y, mean 65 y). Most patients (80%) had a former or current history of heavy
      smoking (20 to 100 pack-years). Three patients had concurrent pulmonary squamous
      cell carcinoma, and 1 had a history of multiple lung cancers. Most lesions were
      small (<2.5 cm) and discovered incidentally. A subset of tumors showed atypical
      morphologic features that would be suggestive of ALT/WDL in soft tissue sites,
      including regions of fibrosis and scattered hyperchromatic stromal cells.
      However, all cases with atypia were CPM negative and behaved in a clinically
      benign manner. Seven cases were tested for HMGA1 and HMGA2 rearrangement; 4
      showed HMGA2 rearrangement, and 1 showed HMGA1 rearrangement, consistent with
      lipomas. Two cases were negative for HMGA1/2 rearrangements. We conclude that
      endobronchial lipomatous neoplasms represent lipomas, even in the presence of
      morphologic features suggestive of ALT/WDL. Ancillary fluorescence in situ
      hybridization testing may be very valuable in the analysis of these rare tumors,
      as true ALT/WDL seem to be very rare or nonexistent at this anatomic site.

PMID- 24121173
TI  - CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin
      tumor and metaplastic pleomorphic adenoma of salivary glands.
AB  - The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or
      CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion
      of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on
      prognosis. However, there are conflicting data on the specificity of this
      translocation, in particular, on its putative occurrence in Warthin tumor (WT) of
      the parotid gland as reported in few previous cases. It was speculated that
      extensive squamous metaplasia could explain the presence of t(11;19)
      translocation in a subset of WTs. We evaluated 76 salivary gland tumors,
      including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with
      squamous and/or mucinous metaplasia, extensive enough morphologically to mimic
      MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene
      break was performed using nested reverse transcription-polymerase chain reaction
      and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed
      metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3
      MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did
      not detect these transcripts or break of MAML2 gene in any case of PA with
      extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC
      were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected
      in 17 and 5 cases, respectively. The FISH method using break-apart probe
      demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In
      contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored
      translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and
      CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.

PMID- 24121175
TI  - Is GATA3 expression maintained in regional metastases?: a study of paired primary
      and metastatic urothelial carcinomas.
AB  - GATA3 has been recognized as a promising marker for primary urothelial carcinoma
      (UC), consistently showing higher expression levels than urothelial markers
      thrombomodulin and uroplakin III. However, expression of GATA3 in comparison with
      UC-associated markers CK7 and p63 has not been systematically studied. Moreover,
      no studies have been conducted to establish GATA3 sensitivity in regional
      metastases. In this study, high-density tissue microarrays were constructed from
      69 matched paired primary and metastatic bladder tumors including pure urothelial
      UCs with papillary (n=48) or flat phenotype (n=9), mixed tumors with
      micropapillary, glandular, small cell, squamous, giant cell, and plasmacytoid
      features (n=9), and 3 adenocarcinomas. GATA3 was expressed in 62/69 (90%) primary
      UC and 64/69 (93%) metastases, with significantly higher staining intensity in
      nodal metastases (P=0.03). In primary tumors, GATA3 was positive in 44/48 (92%)
      papillary UCs, 9/9 (100%) flat UCs, 8/9 (89%) mixed UCs, and 1/3 (33%)
      adenocarcinomas, whereas in metastases these numbers were 45/48 (94%), 9/9
      (100%), 8/9 (89%), and 2/3 (67%), respectively. The majority of positive cases
      showed strong diffuse nuclear reactivity: 75% of primary UCs and 79% of
      metastases. GATA3 sensitivity in primary and metastatic UCs was comparable to
      that of CK7 and superior to that of p63 (P<0.05). GATA3 specificity was computed
      in comparison with its morphologic mimics expressing CK7 and p63, including 208
      primary and 24 metastatic tumors from the lung, cervix, and head and neck
      regions. Strong GATA3 expression was present in 2/51 (4%) cervical carcinomas,
      whereas weak GATA3 expression was present in 7/51 (14%) cervical, 6/74 (8%) head
      and neck cancers, and 2/83 (3%) lung carcinomas. Remaining 191 primary and 24
      metastatic tumors were GATA3 negative. Therefore, specificity of GATA3 calculated
      on the basis of morphologic and immunophenotypic UC mimics from lung, cervix,
      head and neck was 92%. Our findings demonstrate high sensitivity and specificity
      of the GATA3 diagnostic marker, with not only maintained but increased expression
      in regional metastases. 

PMID- 24121176
TI  - Increased mitotic and proliferative activity are associated with worse prognosis
      in papillary tumors of the pineal region.
AB  - Papillary tumors of the pineal region are rare glial tumors located in the
      vicinity of the third ventricle, the clinical behavior of which is often
      aggressive. Little is known about the prognostic markers that might aid to
      identify patients at increased risk for recurrence. Therefore, the prognostic
      value of histopathologic and clinical features was examined in a series of 21
      patients. Median age of the 12 male and 9 female patients was 35 years (range, 10
      to 56 y). On histopathologic examination, all tumors were characterized by loose
      papillary structures and tumor cells forming broad perivascular pseudorosettes
      showing cytokeratin expression. In addition, tumors showed increased cellularity
      (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis
      (n=8; 38%), increased mitotic activity (>=3 mitoses per 10 high-power fields
      [n=10; 48%]), and increased proliferation (Ki67/MIB1 index >=10% [n=8/20; 40%]).
      Gross total resection could be achieved in 13/21 patients (62%). Postoperatively,
      13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence
      free survival was 66 months in 19 patients, for whom detailed follow-up
      information was available. Twelve patients (63%) experienced tumor progression.
      Three patients (16%) died of disease. Among the clinical and histopathologic
      features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to
      70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to
      64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P<0.05).
      Tumors of the 3 patients who had succumbed to disease showed increased mitotic
      and proliferative activity. In conclusion, increased mitotic and proliferative
      activities are associated with worse prognosis in papillary tumors of the pineal
      region. 

PMID- 24121177
TI  - Focally enhanced gastritis in newly diagnosed pediatric inflammatory bowel
      disease.
AB  - Although the significance of focally enhanced gastritis (FEG) as a marker of
      Crohn disease (CD) in adults has been contested, several studies suggest that it
      may be more specific of CD in pediatric patients. This study describes the
      detailed histologic features of FEG in pediatric inflammatory bowel disease (IBD)
      and clarifies its association with CD. A series of 119 consecutive newly
      diagnosed IBD patients (62 CD cases, 57 ulcerative colitis [UC] cases) with upper
      and lower gastrointestinal biopsies were evaluated. The histology of the gastric
      biopsies was reviewed blinded to final diagnoses and compared with age-matched
      healthy controls (n=66). FEG was present in 43% of IBD patients (CD 55% vs. UC
      30%, P=0.0092) and in 5% of controls. Among CD patients, FEG was more common in
      younger patients (73% in children aged 10 y and below, 43% in children above 10 y
      of age, P=0.0358), with the peak in the 5- to 10-year age group (80%). The total
      number of glands involved in each FEG focus was higher in UC (6.4+/-5.1 glands)
      than in CD (4.0+/-3.0 glands, P=0.0409). Amongst the CD cohort, patients with FEG
      were more likely than those without FEG to have active ileitis (79% vs. 40%,
      P=0.0128) and granulomas elsewhere in the gastrointestinal tract (82% vs. 43%,
      P=0.0016). There was no correlation between FEG and other gastrointestinal
      findings of UC. We demonstrate that differences in FEG seen in pediatric CD and
      UC relate to not only their frequencies but also the morphology and relationship
      with other gastrointestinal lesions. Further, FEG is associated with disease
      activity and the presence of granulomas in pediatric CD. 

PMID- 24121178
TI  - Myxoinflammatory fibroblastic sarcoma: a clinicopathologic analysis of 104 cases,
      with emphasis on predictors of outcome.
AB  - In this study, we examine the clinicopathologic features of 104 cases of
      myxoinflammatory fibroblastic sarcoma (MIFS), a low-grade, inflammatory
      fibromyxoid tumor with a predilection to distal extremity soft tissue, and
      attempt to identify factors predictive of aggressive behavior. The study cohort
      consisted of 49 male and 55 female patients ranging in age from 17 to 83 (mean,
      42; median, 39) years. The tumor arose primarily on the dorsal aspect of the
      distal extremities as a solitary and usually painless mass. Tumors ranged in size
      from 0.5 to 15 (mean, 3.2; median; 2.4) cm. Microscopically, tumors consisted of
      variably cellular and inflamed fibromyxoid tissue growing as a lobulated mass or
      as multiple nodules within subcutaneous tissue or along tendinofascial planes.
      Tumor cells ranged from plump spindled to more epithelioid cells with enlarged,
      vesicular nuclei. Characteristic of the process was a strikingly bizarre cell
      with an inclusion body-like nucleolus (85% of cases) and/or a smudgy
      hyperchromatic nucleus (51%) present in all but 7 cases. The mitotic rate per 50
      high-power field ranged from 0 to 13 (mean, 2,9; median, 2) mitoses. Twenty-two
      tumors demonstrated 1 or more of the following atypical features: (1) foci with
      complex sarcoma-like vasculature; (2) hypercellular areas; and (3) increased
      mitotic activity or atypical mitotic figures. Immunohistochemically, tumor cells
      demonstrated immunoreactivity for vimentin (100%), D2-40 (86%), CD34 (50%),
      keratin(s) (33%), CD68 (27%), actin(s) (26%), desmin (9%), S-100 protein (7%),
      and epithelial membrane antigen (6%). Thirty of 59 patients (51%) with follow-up
      data suffered (at least) 1 local recurrence, and 1 patient developed metastatic
      disease after multiple local recurrences. Completeness of initial surgical
      excision was the only clinicopathologic parameter that statistically correlated
      with a lower incidence of recurrence (P=0.004). Histologically atypical MIFS
      recurred more often than conventional tumors (67% vs. 47%), but the difference
      was not statistically significant (P=0.35). Our study shows that histologic
      features often associated with more aggressive sarcomas do not substantially
      impact the morbidity of MIFS, and complete surgical excision provides the best
      chance for disease-free survival. 

PMID- 24121179
TI  - Cystic hypersecretory (in situ) carcinoma of the breast: a clinicopathologic and
      immunohistochemical characterization of 10 cases with clinical follow-up.
AB  - Cystic hypersecretory carcinoma (CHC) is an uncommon variant of ductal carcinoma
      in situ characterized by, among other features, the presence of luminal secretion
      resembling thyroidal colloid. CHC is thought to behave in an indolent manner but
      has the potential to give rise to invasive carcinoma, which is often poorly
      differentiated. We studied the immunohistochemical, clinical, and morphologic
      features of 10 cases of CHC. All patients were women averaging 62.8 years in age
      (range, 47 to 79 y). The clinical/radiographic presentation was a mass (5/10),
      calcifications (3/10), bloody nipple discharge (1/10), and unknown (1/10).
      Microscopic size of CHC ranged from 0.2 to 2.7 cm (mean, 0.9 cm). Micropapillary
      growth was present in all cases. Nuclear grade was intermediate (5/10) or high
      (5/10). One case also showed microinvasive carcinoma. All cases arose in a
      background of cystic hypersecretory hyperplasia (CHH) and/or CHH with atypia. CHC
      was ER in 8/10 cases (ER+/PR+, 4/10; ER+/PR+, 4/10). Two cases were ER-/PR-,
      including the case with microinvasive carcinoma. All were HER2-. Androgen
      receptor was expressed in 3/10 (30%) cases. Myoepithelial stains p63, smooth
      muscle myosin, and CK5 showed circumferential staining in 9/10 (90%) cases,
      whereas 1 case was negative for p63, smooth muscle myosin, and CK5 in both CHC
      and adjacent CHH. Basal-like carcinoma markers EGFR, CK14, and CK5 were negative
      in all cases, with the exception of 1 case that was positive for EGFR. Four
      patients with follow-up information showed no evidence of disease (mean, 5.5 y).
      CHC is a distinct variant of ductal carcinoma in situ that arises in a background
      of CHH and is characterized by micropapillary growth, intermediate-grade to high
      grade nuclei, and luminal colloid-like secretion. CHC is usually ER and HER2-.
      Negative or discontinuous reactivity with myoepithelial markers may be seen,
      despite its in situ nature. CHC usually behaves in a nonaggressive manner as was
      seen in our patients who were all free from disease at last follow-up.

PMID- 24121180
TI  - Does facial expressivity count? How typically developing children respond
      initially to children with autism.
AB  - Research investigating expressivity in children with autism spectrum disorder has
      reported flat affect or bizarre facial expressivity within this population;
      however, the impact expressivity may have on first impression formation has
      received little research input. We examined how videos of children with autism
      spectrum disorder were rated for expressivity by adults blind to the condition.
      We further investigated the friendship ratings given by 44 typically developing
      children to the same videos. These ratings were compared to friendship ratings
      given to video clips of typically developing children. Results demonstrated that
      adult raters, blind to the diagnosis of the children in the videos, rated
      children with autism spectrum disorder as being less expressive than typically
      developing children. These autism spectrum disorder children were also rated
      lower than typically developing children on all aspects of our friendship
      measures by the 44 child raters. Results suggest that impression formation is
      less positive towards children with autism spectrum disorder than towards
      typically developing children even when exposure time is brief.

PMID- 24121181
TI  - Longitudinal follow-up of factors associated with food selectivity in children
      with autism spectrum disorders.
AB  - The objective of this study was to examine food selectivity in children with
      autism spectrum disorders longitudinally. Additionally explored were the
      stability of the relationship between food selectivity and sensory over
      responsivity from time 1 to time 2 and the association between food selectivity
      and restricted and repetitive behavior at time 2. A total of 52 parents of
      children with autism were surveyed approximately 20 months after completing an
      initial questionnaire. First and second surveys each contained identical parent
      response item to categorize food selectivity level and a scale to measure sensory
      over-responsivity. A new scale to measure restricted and repetitive behaviors was
      added at time 2. Results comparing time 1 to time 2 indicated no change in food
      selectivity level and a stable, significant relationship between food selectivity
      and sensory over-responsivity. The measure of restrictive and repetitive behavior
      (time 2) was found to significantly predict membership in the severe food
      selectivity group. However, when sensory over-responsivity and both restricted
      and repetitive behaviors were included in the regression model, only sensory over
      responsivity significantly predicted severe food selectivity. These results
      support conclusions about the chronicity of food selectivity in young children
      with autism and the consistent relationship between food selectivity and sensory
      over-responsivity. 

PMID- 24121182
TI  - Influence of aging on nitrogen accretion during critical illness.
AB  - BACKGROUND: Aging adversely affects nitrogen accretion during health, but its
      effect during critical illness is unknown. Nitrogen balance (NB) response to
      varying protein intakes was compared between critically ill, older and younger
      patients. METHODS: Adult patients admitted to the trauma intensive care unit,
      given enteral or parenteral nutrition, and who had a NB determination within 5-14
      days after injury were evaluated. Patients with renal or hepatic disease were
      excluded. Patients were categorized as older (>=60 years) or younger (18-59 years
      of age). Data are given as mean +/- SD or median [interquartile range]. RESULTS:
      Fifty-four older (69 [65, 77] years) and 195 younger (35 [27, 47] years) patients
      were evaluated. NB was blunted for the older patients with an observed trending
      improvement in NB from -13.5 +/- 5.5 to -5.6 +/- 8.8 g/d (P = NS) noted at 1.5
      1.99 g/kg/d. NB improved from -22.2 +/- 8.2 to -11.8 +/- 9.9 g/d (P = .05) at 1
      1.49 g/kg/d and modestly thereafter for each 0.5-g/kg/d increase in protein
      intake for the younger patients. Serum urea nitrogen concentration during the NB
      was highly variable but overall greater for the older patients (20 [14, 33] vs 15
      [10, 20] mg/dL, P = .001). CONCLUSIONS: Improvement in nitrogen accretion was
      blunted at lower protein intakes in critically ill, older patients compared with
      younger patients. Individualization of protein intake is warranted.

PMID- 24121184
TI  - Pretreatment with an intravenous lipid emulsion increases plasma eicosapentanoic
      acid and downregulates leukotriene b4, procalcitonin, and lymphocyte
      concentrations after open heart surgery in infants.
AB  - BACKGROUND: The effect of providing a lipid emulsion containing medium-chain
      triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not
      widely studied. This study investigated lipid emulsion effects on plasma
      phospholipids and immune biomarkers. MATERIALS AND METHODS: Thirty-two infants
      undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition
      (PN) were randomized to receive either soybean oil (control, n = 16) or a
      50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was
      administered for 3 days preoperatively and 10 days postoperatively. Fatty acids,
      procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at
      baseline, before surgery, and days 1, 7 and 10 after surgery. RESULTS: PCT was
      significantly lower in the treatment vs control group 1 day postoperatively (P =
      .01). The treatment group exhibited a lower omega-6 to omega-3 ratio (P = .0001)
      and a higher omega-3 concentration at all postoperative study periods (P = .001).
      Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid
      (EPA) on days 7 and 10, while alpha-linolenic acid, arachidonic acid, and
      docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA
      concentration was associated with a decrease in plasma phospholipid LTB4
      concentration (P < .05). On postoperative day 10, treatment infants with high
      Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte
      concentration (P < .05). CONCLUSION: These findings suggest that treating infants
      undergoing CPB with a lipid emulsion containing omega-3 improves fatty acid
      status and results in a lower inflammatory response after surgery. Overall, this
      alternative omega-3-enriched lipid emulsion may benefit clinical outcomes of
      critically ill infants after cardiac surgery.

PMID- 24121183
TI  - Bombesin improves adaptive immunity of the salivary gland during parenteral
      nutrition.
AB  - BACKGROUND: The parotid and submandibular salivary glands are gut-associated
      lymphoid tissues (GALTs) that secrete immune compounds into the oral cavity.
      Parenteral nutrition (PN) without enteral stimulation decreases GALT function,
      including intestinal lymphocyte counts and secretory immunoglobulin A (sIgA)
      levels. Since the neuropeptide bombesin (BBS), a gastrin-releasing peptide
      analogue, stimulates intestinal function and restores GALT parameters, we
      hypothesized that PN + BBS would stimulate parotid and salivary gland IgA levels,
      T lymphocytes, and IgA plasma cell counts compared with PN alone. METHODS: Male
      (Institute of Cancer Research) ICR mice received intravenous catheters and were
      randomized to chow with saline, PN, or PN + BBS (15 ug/tid/mouse) for 5 days
      (8/group), 2 days after cannulation. Salivary glands were weighed and either
      frozen for IgA and amylase analysis or fixed for histological analysis of acinar
      cells, IgA+ plasma cells, and T lymphocytes. Small intestinal wash fluid was
      collected for IgA regression analysis with salivary glands. RESULTS: PN reduced
      organ weight, acinar cell size, and amylase activity compared with chow; BBS had
      no significant effects on these parameters. Compared with chow, PN significantly
      reduced salivary gland IgA levels, IgA+ plasma cells, and T lymphocytes. PN + BBS
      significantly elevated IgA and restored cellularity compared with PN. Salivary
      gland tissue homogenate IgA levels significantly correlated with intestinal fluid
      IgA levels. CONCLUSIONS: Compared with chow, PN results in atrophy of the
      salivary glands characterized by reduced amylase, IgA, and immune cellularity.
      BBS has no effect on acinar cells or amylase activity compared with PN but
      maintains tissue IgA and plasma cells and T-lymphocyte numbers compared with
      chow.

PMID- 24121185
TI  - Effect of menthol in experimentally induced ulcers: pathways of gastroprotection.
AB  - Based on ethnopharmacological indications that Mentha species may be used in the
      treatment of gastrointestinal diseases, this study aimed to characterize the
      gastroprotective mechanisms of menthol (ME), the major compound of the essential
      oil from species of the genus Mentha. The gastroprotective action of ME was
      analyzed in gastric ulcers that were induced by ethanol or indomethacin in Wistar
      male rats. The mechanisms responsible for the gastroprotective effect were
      assessed by analyzing the amount of mucus secreted, involvement of non-protein
      sulfhydryl (NP-SH) compounds, involvement of calcium ion channels and
      NO/cGMP/K(+)ATP pathway, gastric antisecretory activity and the prostaglandin E2
      (PGE2) production. The anti-diarrheal activity and acute toxicity of ME were also
      evaluated. Oral treatment with ME (50mg/kg) offered 88.62% and 72.62% of
      gastroprotection against ethanol and indomethacin, respectively. There was an
      increased amount of mucus and PGE2 production. The gastroprotective activity of
      ME involved NP-SH compounds and the stimulation of K(+)ATP channels, but not the
      activation of calcium ion channels or the production of NO. The oral
      administration of ME induced an antisecretory effect as it decreased the H(+)
      concentration in gastric juice. ME displayed anti-diarrheal and antiperistaltic
      activity. There were no signs of toxicity in the biochemical analyses performed
      in the rats' serum. These results demonstrated that ME provides gastroprotective
      and anti-diarrheal activities with no toxicity in rats. 

PMID- 24121186
TI  - Cytotoxicity of nitroxyl (HNO/NO-) against normal and cancer human cells.
AB  - Nitroxyl (HNO/NO(-)) is a molecule which results from one-electron reduction of
      nitric oxide (NO). It is considered to be a pharmacologically important particle
      because of its cardiovascular effects and potential anticancer activity. Due to
      molecule instability studies on nitroxyl biological activity require the use of
      donor compounds. In the present study Angeli's salt (Na2N2O3) was used as the
      nitroxyl donor and cytotoxicity of HNO/NO(-) against human lymphocytes and A549
      and HT29 cancer cells was examined. The studies were performed under different pH
      conditions (pH 6.2 and 7.4) because it was suggested that formation of HNO and
      its toxicological effects may be stronger in tissues subjected to acidosis such
      as cancerous ones. It was shown that nitroxyl exerted cytotoxic effect against
      all three types of cells. Nitroxyl induced both apoptotic and necrotic cell
      death. The cytotoxic effect analyzed directly after cell treatment was stronger
      than that observed 24h later. Differences in cell sensitivity to nitroxyl were
      observed--proliferating lymphocytes were the most sensitive cells. It was also
      shown that pro-oxidant activity of nitroxyl was stronger under slightly acidic
      conditions as compared to physiological pH but this difference was not always
      reflected in the observed cytotoxic effect, especially when the effect was
      measured 24h after cell treatment. Thus, relatively high toxicity of nitroxyl
      against normal cells and its ability to induce not only apoptotic but also
      necrotic cell death make use of this molecule in cancer therapy questionable.

PMID- 24121187
TI  - A metabonomic investigation of the effects of 60 days exposure of rats to two
      types of pyrethroid insecticides.
AB  - Type I and II pyrethroid insecticides display different neurotoxicity. To
      investigate the long-term (60 days exposure) metabolic effect of the two types of
      pyrethroid insecticides deltamethrin and permethrin, (1)H nuclear magnetic
      resonance (NMR) spectroscopy-based metabonomics was used to analyze the
      biochemical composition of urine and serum samples from rats administrated daily
      with deltamethrin or permethrin for 60 consecutive days, and principal component
      analysis used to visualize similarities and differences in the resultant
      biochemical profiles. Rats treated with either deltamethrin or permethrin
      displayed increased levels of urinary acetate, dimethylamine, dimethylglycine,
      trimethylamine and serum free amino acids, and decreased urinary 2-oxoglutarate,
      all of which are indicative of kidney lesions and nephrotoxicity. The reduced
      excretion of tricarboxylic acid cycle intermediates, together with increased 3-D
      hydroxybutyrate, acetate, and lactate in treated rats could suggest disturbance
      of the energy metabolism, including an increased rate of anaerobic glycolysis,
      enhanced fatty acid beta-oxidation and ketogenesis. These results show that these
      two types of insecticides have similarities in the urine and serum spectra,
      indicating that similar metabolic pathways are perturbed by the insecticides,
      which induced hepatotoxicity and nephrotoxicity. This approach may lead to the
      discovery of novel biomarkers of pyrethroids toxicity and thereby provide new
      insights into the toxicological mechanisms of pesticides pyrethroids.

PMID- 24121189
TI  - Surveillance for brain metastases in patients receiving systemic therapy for
      advanced melanoma.
AB  - The objectives of this study were to determine the cumulative incidence and
      timing of new brain metastases over the course of systemic therapy for metastatic
      melanoma and to identify prognostic factors for brain metastases. Chemo-naive
      patients underwent computed tomography or MRI of the brain every 6 weeks. The
      cumulative incidence of confirmed brain metastases was calculated at 12-week
      intervals. Univariable and multivariable competing risk regression models were
      used to assess the association between the development of brain metastases and
      potential risk factors of interest. Cumulative incidence with competing risk and
      competing risk regression was used to assess the brain metastasis-free interval
      from the time of diagnosis of stage IV disease. The clinical characteristics of
      the 315 patients with brain metastases were compared with those of 370 brain
      metastasis-free patients. Among patients with brain metastases, a significantly
      higher proportion had stage M1b and M1c disease at diagnosis compared with stage
      M1a and a greater proportion had metastatic disease in three or more visceral
      sites. Significantly shorter brain metastasis-free intervals were found in these
      patients compared with patients with M1a disease and those with no visceral
      metastases. More than 80% of the 230 patients who developed brain metastases
      during systemic therapy had their brain metastases confirmed within 60 weeks from
      the onset of advanced melanoma. Imaging studies at 12-week intervals for 60 weeks
      after the diagnosis of advanced melanoma will detect brain metastases in most of
      the patients who will eventually develop them. 

PMID- 24121188
TI  - The development and maintenance of drug addiction.
AB  - What is the defining property of addiction? We dust off a several-decades-long
      debate about the relative importance of two forms of reinforcement-positive
      reinforcement, subjectively linked to drug-induced euphoria, and negative
      reinforcement, subjectively linked to the alleviation of pain-both of which
      figure importantly in addiction theory; each of these forms has dominated
      addiction theory in its time. We agree that addiction begins with the formation
      of habits through positive reinforcement and that drug-opposite physiological
      responses often establish the conditions for negative reinforcement to come into
      play at a time when tolerance, in the form of increasing reward thresholds,
      appears to develop into positive reinforcement. Wise's work has tended to focus
      on positive-reinforcement mechanisms that are important for establishing drug
      seeking habits and reinstating them quickly after periods of abstinence, whereas
      Koob's work has tended to focus on the negative-reinforcement mechanisms that
      become most obvious in the late stages of sustained addiction. While we tend to
      agree with each other about the early and late stages of addiction, we hold
      different views as to (i) the point between early and late at which the diagnosis
      of 'addiction' should be invoked, (ii) the relative importance of positive and
      negative reinforcement leading up to this transition, and (iii) the degree to
      which the specifics of negative reinforcement can be generalized across the range
      of addictive agents.

PMID- 24121190
TI  - The treatment of melanoma brain metastases before the advent of targeted
      therapies: associations between therapeutic choice, clinical symptoms and outcome
      with survival.
AB  - The management of melanoma brain metastases (MBM) includes different therapeutic
      modalities, such as surgery, radiotherapy and chemotherapy. Despite the choice of
      treatments, survival remains poor, exceeding 1 year only in patients with
      solitary metastases and absence of extracranial disease. A total of 115
      consecutive MBM patients observed between 1994 and 2010 were included in an
      historical cohort study. Demographic, clinical data and tumour characteristics
      were collected and survival status was ascertained across the follow-up window.
      The statistical associations between individual and tumour data and overall
      survival were investigated using Kaplan-Meier survival function and Cox's
      multiple regression analysis. The median survival was 4.3 months (95% confidence
      interval 2.6-6.1). Patients who underwent surgery or stereotactic radiosurgery
      showed a significantly (P<0.001) better prognosis than those who received
      chemotherapy and/or radiotherapy or supportive therapies. Patients without
      clinical symptoms experienced a statistically significant better survival
      (P=0.02) than patients with clinical symptoms; analogue difference was observed
      to be in favour of patients whose symptoms improved after the first treatment of
      MBM (P<0.001). The presence of symptoms, clinical outcome and first treatment
      received were the only independent variables to predict survival. Patients who
      cannot receive surgery or stereotactic radiosurgery have the worst overall
      survival. 

PMID- 24121192
TI  - Therapeutic bioactive microcarriers: co-delivery of growth factors and stem cells
      for bone tissue engineering.
AB  - Novel microcarriers made of sol-gel-derived bioactive glasses were developed for
      delivering therapeutic molecules effectively while cultivating stem cells for
      bone tissue engineering. Silica sols with varying concentration of Ca (0-30
      mol.%) were formulated into microspheres ranging from 200 to 300 MUm under
      optimized conditions. A highly mesoporous structure was created, with mesopore
      sizes of 2.5-6.3 nm and specific surface areas of 420-710 m(2)g(-1), which was
      highly dependent on the Ca concentration. Therapeutic molecules could be
      effectively loaded within the mesoporous microcarriers during microsphere
      formulation. Cytochrome C (cyt C), used as a model protein for the release study,
      was released in a highly sustainable manner, with an almost zero-order kinetics
      over a period of months; the amount released was ~2% at 9 days, and 15% at 40
      days. A slight increase in the release rate was observed in the microcarrier
      containing Ca, which was related to the dissolution rate and pore size. The
      presence of Ca accelerated the formation of hydroxyapatite on the surface of the
      microcarriers. Cells cultured on the bioactive microcarriers were well adhered
      and distributed, and proliferated actively, confirming the three-dimensional
      substrate role of the microcarriers. An in vivo study performed in a rat
      subcutaneous model demonstrated the satisfactory biocompatibility of the prepared
      microspheres. As a therapeutic target molecule, basic fibroblast growth factor
      (bFGF) was incorporated into the microcarriers. A slow release pattern similar to
      that of cyt C was observed for bFGF. Cells adhered and proliferated to
      significantly higher levels on the bFGF-loaded microcarriers, demonstrating the
      effective role of bFGF in cell proliferative potential. It is believed that the
      developed mesoporous bioactive glass microspheres represent a new class of
      therapeutic cell delivery carrier, potentially useful in the sustainable delivery
      of therapeutic molecules such as growth factors, as well as in the support of
      stem cell proliferation and osteogenesis for bone tissue engineering.

PMID- 24121193
TI  - Nanoparticle release from dental composites.
AB  - Dental composites typically contain high amounts (up to 60 vol.%) of nanosized
      filler particles. There is a current concern that dental personnel (and patients)
      may inhale nanosized dust particles (<100 nm) during abrasive procedures to
      shape, finish or remove restorations but, so far, whether airborne nanoparticles
      are released has never been investigated. In this study, composite dust was
      analyzed in real work conditions. Exposure measurements of dust in a dental
      clinic revealed high peak concentrations of nanoparticles in the breathing zone
      of both dentist and patient, especially during aesthetic treatments or treatments
      of worn teeth with composite build-ups. Further laboratory assessment confirmed
      that all tested composites released very high concentrations of airborne
      particles in the nanorange (>10(6)cm(-3)). The median diameter of airborne
      composite dust varied between 38 and 70 nm. Electron microscopic and energy
      dispersive X-ray analysis confirmed that the airborne particles originated from
      the composite, and revealed that the dust particles consisted of filler particles
      or resin or both. Though composite dust exhibited no significant oxidative
      reactivity, more toxicological research is needed. To conclude, on manipulation
      with the bur, dental composites release high concentrations of nanoparticles that
      may enter deeply into the lungs.

PMID- 24121194
TI  - Hierarchical modelling of in situ elastic deformation of human enamel based on
      photoelastic and diffraction analysis of stresses and strains.
AB  - Human enamel is a typical hierarchical mineralized tissue with a two-level
      composite structure. To date, few studies have focused on how the mechanical
      behaviour of this tissue is affected by both the rod orientation at the
      microscale and the preferred orientation of mineral crystallites at the
      nanoscale. In this study, wide-angle X-ray scattering was used to determine the
      internal lattice strain response of human enamel samples (with differing rod
      directions) as a function of in situ uniaxial compressive loading. Quantitative
      stress distribution evaluation in the birefringent mounting epoxy was performed
      in parallel using photoelastic techniques. The resulting experimental data was
      analysed using an advanced multiscale Eshelby inclusion model that takes into
      account the two-level hierarchical structure of human enamel, and reflects the
      differing rod directions and orientation distributions of hydroxyapatite
      crystals. The achieved satisfactory agreement between the model and the
      experimental data, in terms of the values of multidirectional strain components
      under the action of differently orientated loads, suggests that the multiscale
      approach captures reasonably successfully the structure-property relationship
      between the hierarchical architecture of human enamel and its response to the
      applied forces. This novel and systematic approach can be used to improve the
      interpretation of the mechanical properties of enamel, as well as of the textured
      hierarchical biomaterials in general. 

PMID- 24121191
TI  - Molecular engineering of glycosaminoglycan chemistry for biomolecule delivery.
AB  - Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides that
      interact with a variety of positively charged growth factors. In this review
      article the effects of engineering GAG chemistry for molecular delivery
      applications in regenerative medicine are presented. Three major areas of focus
      at the structure-function-property interface are discussed: (1) macromolecular
      properties of GAGs; (2) effects of chemical modifications on protein binding; (3)
      degradation mechanisms of GAGs. GAG-protein interactions can be based on: (1) GAG
      sulfation pattern; (2) GAG carbohydrate conformation; (3) GAG polyelectrolyte
      behavior. Chemical modifications of GAGs, which are commonly performed to
      engineer molecular delivery systems, affect protein binding and are highly
      dependent on the site of modification on the GAG molecules. The rate and mode of
      degradation can determine the release of molecules as well as the length of GAG
      fragments to which the cargo is electrostatically coupled and eventually released
      from the delivery system. Overall, GAG-based polymers are a versatile biomaterial
      platform offering novel means to engineer molecular delivery systems with a high
      degree of control in order to better treat a range of degenerated or injured
      tissues. 

PMID- 24121195
TI  - The effect of nanoparticle degradation on amphiphilic polymer-coated quantum dot
      toxicity: the importance of particle functionality assessment in toxicology
      [corrected].
AB  - Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of
      interest in technological and biomedical research, given their potent fluorescent
      properties. However, the use of heavy-metal-containing nanoparticles remains an
      issue of debate. The possible toxic effects of quantum dots remain a hot research
      topic and several questions such as possible intracellular degradation of quantum
      dots and the effect thereof on both cell viability and particle functionality
      remain unresolved. In the present work, amphiphilic polymer [corrected] coated
      CdSe/ZnS quantum dots were synthesized and characterized, after which their
      effects on cultured cells were evaluated using a multiparametric setup. The data
      reveal that the quantum dots are taken up through endocytosis and when exposed to
      the low pH of the endosomal structures, they partially degrade and release
      cadmium ions, which lowers their fluorescence intensity and augments particle
      toxicity. Using the multiparametric method, the quantum dots were evaluated at
      non-toxic doses in terms of their ability to visualize labeled cells for longer
      time periods. The data revealed that comparing different particles in terms of
      their applied dose is challenging, likely due to difficulties in obtaining
      accurate nanoparticle concentrations, but evaluating particle toxicity in terms
      of their biological functionality enables an easy and straightforward comparison.

PMID- 24121197
TI  - Chitosan-based dressings loaded with neurotensin--an efficient strategy to
      improve early diabetic wound healing.
AB  - One important complication of diabetes mellitus is chronic, non-healing diabetic
      foot ulcers (DFUs). This study aims to develop and use dressings based on
      chitosan derivatives for the sustained delivery of neurotensin (NT), a
      neuropeptide that acts as an inflammatory modulator in wound healing. Three
      different derivatives, namely N-carboxymethyl chitosan, 5-methyl pyrrolidinone
      chitosan (MPC) and N-succinyl chitosan, are presented as potential biomaterials
      for wound healing applications. Our results show that MPC has the best fluid
      handling capacity and delivery profile, also being non-toxic to Raw 264.7 and
      HaCaT cells. NT-loaded and non-loaded MPC dressings were applied to
      control/diabetic wounds to evaluate their in vitro/in vivo performance. The
      results show that the former induced more rapid healing (50% wound area
      reduction) in the early phases of wound healing in diabetic mice. A NT-loaded MPC
      foam also reduced expression of the inflammatory cytokine TNF-alpha (P<0.001) and
      decreased the amount of inflammatory infiltrate on day 3. On day 10 MMP-9 was
      reduced in diabetic skin (P<0.001), significantly increasing fibroblast migration
      and collagen (COL1A1, COL1A2 and COL3A1) expression and deposition. These results
      suggest that MPC-based dressings may work as an effective support for sustained
      NT release to reduce DFUs.

PMID- 24121198
TI  - Functional implications of the Golgi and microtubular network in gonadotropes.
AB  - In contrast to the widely accepted images of the Golgi apparatus as a cup-like
      shape, the Golgi in pituitary gonadotropes is organized as a spherical shape in
      which the outer and inner faces are cis- and trans-Golgi elements, respectively.
      At the center of the spherical Golgi, a pair of centrioles is situated as a
      microtubule-organizing center from which radiating microtubules isotropically
      extend toward the cell periphery. This review focuses on the significance of the
      characteristic organization of the Golgi and microtubule network in gonadotropes,
      considering the roles of microtubule-dependent membrane transport in the
      formation and maintenance of the Golgi structure. Because the highly symmetrical
      organization of the Golgi is possibly perturbed in response to experimental
      treatments of gonadotropes, monitoring of the Golgi structure in gonadotropes
      under various experimental conditions will be a novel in vivo approach to
      elucidate the biogenesis of the Golgi apparatus. 

PMID- 24121196
TI  - Designing protein-based biomaterials for medical applications.
AB  - Biomaterials produced by nature have been honed through billions of years,
      evolving exquisitely precise structure-function relationships that scientists
      strive to emulate. Advances in genetic engineering have facilitated extensive
      investigations to determine how changes in even a single peptide within a protein
      sequence can produce biomaterials with unique thermal, mechanical and biological
      properties. Elastin, a naturally occurring protein polymer, serves as a model
      protein to determine the relationship between specific structural elements and
      desirable material characteristics. The modular, repetitive nature of the protein
      facilitates the formation of well-defined secondary structures with the ability
      to self-assemble into complex three-dimensional architectures on a variety of
      length scales. Furthermore, many opportunities exist to incorporate other protein
      based motifs and inorganic materials into recombinant protein-based materials,
      extending the range and usefulness of these materials in potential biomedical
      applications. Elastin-like polypeptides (ELPs) can be assembled into 3-D
      architectures with precise control over payload encapsulation, mechanical and
      thermal properties, as well as unique functionalization opportunities through
      both genetic and enzymatic means. An overview of current protein-based materials,
      their properties and uses in biomedicine will be provided, with a focus on the
      advantages of ELPs. Applications of these biomaterials as imaging and therapeutic
      delivery agents will be discussed. Finally, broader implications and future
      directions of these materials as diagnostic and therapeutic systems will be
      explored. 

PMID- 24121199
TI  - Biased signalling in follicle stimulating hormone action.
AB  - Follicle-stimulating hormone (FSH) plays a crucial role in the control of
      reproduction by specifically binding to and activating a membrane receptor (FSHR)
      that belongs to the G protein-coupled receptor (GPCR) family. Similar to all
      GPCRs, FSHR activation mechanisms have generally been viewed as a two-state
      process connecting a unique FSH-bound active receptor to the Gs/cAMP pathway.
      Over the last decade, paralleling the breakthroughs that were made in the GPCR
      field, our understanding of FSH actions at the molecular level has dramatically
      changed. There are numerous facts indicating that the active FSHR is connected to
      a complex signalling network rather than the sole Gs/cAMP pathway. Consistently,
      the FSHR probably exists in equilibrium between multiple conformers, a subset of
      them being stabilized upon ligand binding. Importantly, the nature of the
      stabilized conformers of the receptor directly depends on the chemical structure
      of the ligand bound. This implies that it is possible to selectively control the
      intracellular signalling pathways activated by using biased ligands. Such biased
      ligands can be of different nature: small chemical molecules, glycosylation
      variants of the hormone or antibody/hormone complexes. Likewise, mutations or
      polymorphisms affecting the FSHR can also lead to stabilization of preferential
      conformers, hence to selective modulation of signalling pathways. These emerging
      notions offer a new conceptual framework that could potentially lead to the
      development of more specific drugs while also improving the way FSHR
      mutants/variants are functionally characterized. 

PMID- 24121200
TI  - Integration-free methods for generating induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells can be generated from mouse or human
      fibroblasts by exogenous expression of four factors, Oct4, Sox2, Klf4 and c-Myc,
      and hold great potential for transplantation therapies and regenerative medicine.
      However, use of retroviral vectors during iPS cell generation has limited the
      technique's clinical application due to the potential risks resulting from genome
      integration of transgenes, including insertional mutations and altered
      differentiation potentials of the target cells, which may lead to pathologies
      such as tumorigenesis. Here we review recent progress in generating safer
      transgene-free or integration-free iPS cells, including the use of non
      integrating vectors, excision of vectors after integration, DNA-free delivery of
      factors and chemical induction of pluripotency. 

PMID- 24121201
TI  - Regional differences in SERT occupancy after acute and prolonged SSRI intake
      investigated by brain PET.
AB  - Blocking of the serotonin transporter (SERT) represents the initial mechanism of
      action of selective serotonin reuptake inhibitors (SSRIs) which can be visualized
      due to the technical proceedings of SERT occupancy studies. When compared to the
      striatum, higher SERT occupancy in the midbrain and lower values in the thalamus
      were reported. This indicates that occupancy might be differently distributed
      throughout the brain, which is supported by preclinical findings indicating a
      regionally varying SERT activity and antidepressant drug concentration. The
      present study therefore aimed to investigate regional SERT occupancies with
      positron emission tomography and the radioligand [(11)C]DASB in 19 depressed
      patients after acute and prolonged intake of oral doses of either 10mg/day
      escitalopram or 20mg/day citalopram. Compared to the mean occupancy across
      cortical and subcortical regions, we detected increased SERT occupancies in
      regions commonly associated with antidepressant response, such as the subgenual
      cingulate, amygdala and raphe nuclei. When acute and prolonged drug intake was
      compared, SERT occupancies increased in subcortical areas that are known to be
      rich in SERT. Moreover, SERT occupancy in subcortical brain areas after prolonged
      intake of antidepressants was predicted by plasma drug levels. Similarly,
      baseline SERT binding potential seems to impact SERT occupancy, as regions rich
      in SERT showed greater binding reduction as well as higher residual binding.
      These findings suggest a region-specific distribution of SERT blockage by SSRIs
      and relate the postulated link between treatment response and SERT occupancy to
      certain brain regions such as the subgenual cingulate cortex. 

PMID- 24121202
TI  - Structurally-informed Bayesian functional connectivity analysis.
AB  - Functional connectivity refers to covarying activity between spatially segregated
      brain regions and can be studied by measuring correlation between functional
      magnetic resonance imaging (fMRI) time series. These correlations can be caused
      either by direct communication via active axonal pathways or indirectly via the
      interaction with other regions. It is not possible to discriminate between these
      two kinds of functional interaction simply by considering the covariance matrix.
      However, the non-diagonal elements of its inverse, the precision matrix, can be
      naturally related to direct communication between brain areas and interpreted in
      terms of partial correlations. In this paper, we propose a Bayesian model for
      functional connectivity analysis which allows estimation of a posterior density
      over precision matrices, and, consequently, allows one to quantify the
      uncertainty about estimated partial correlations. In order to make model
      estimation feasible it is assumed that the sparseness structure of the precision
      matrices is given by an estimate of structural connectivity obtained using
      diffusion imaging data. The model was tested on simulated data as well as resting
      state fMRI data and compared with a graphical lasso analysis. The presented
      approach provides a theoretically solid foundation for quantifying functional
      connectivity in the presence of uncertainty. 

PMID- 24121203
TI  - The influence of puberty on subcortical brain development.
AB  - Puberty is characterized by hormonal, physical and psychological transformation.
      The human brain undergoes significant changes between childhood and adulthood,
      but little is known about how puberty influences its structural development.
      Using a longitudinal sample of 711 magnetic resonance imaging scans from 275
      individuals aged 7-20years, we examined how subcortical brain regions change in
      relation to puberty. Our regions of interest included the amygdala, hippocampus
      and corpus striatum including the nucleus accumbens (NA), caudate, putamen and
      globus pallidus (GP). Pubertal development was significantly related to
      structural volume in all six regions in both sexes. Pubertal development and age
      had both independent and interactive influences on volume for the amygdala,
      hippocampus and putamen in both sexes, and the caudate in females. There was an
      interactive puberty-by-age effect on volume for the NA and GP in both sexes, and
      the caudate in males. These findings suggest a significant role for puberty in
      structural brain development. 

PMID- 24121206
TI  - Black silicon SERS substrate: effect of surface morphology on SERS detection and
      application of single algal cell analysis.
AB  - In this study, we have investigated the effect of the surface morphology of the
      black silicon substrate on surface enhanced Raman spectroscopy (SERS) and
      explored its application of single algal cell detection. By adjusting the O2 and
      SF6 flow rates in the cryogenic plasma etching process, different surface
      morphologies of the black silicon substrate was produced without performing the
      lithographic process. It was found the Raman signals were better enhanced as the
      tip density of the black silicon substrate increased. In addition, as the
      thickness of the deposited gold layer increased, the SERS effect increased as
      well, which could be owing to the generation of more hot spots by bridging
      individual silicon tips through deposition of gold layer. For the black silicon
      substrate with tip density of 30 tips/MUm(2) and covered by 400 nm deposited gold
      layer, the detection limit of 10 fM R6G solution concentration with uniform SERS
      effect across the substrate was achieved. Furthermore, detection of individual
      algal cell (Chlorella vulgaris) was performed at the SERS substrate as fabricated
      and the Raman signals of carotenoid and lipid were substantially enhanced.

PMID- 24121205
TI  - Lipase-nanoporous gold biocomposite modified electrode for reliable detection of
      triglycerides.
AB  - For triglycerides biosensor design, protein immobilization is necessary to create
      the interface between the enzyme and the electrode. In this study, a glassy
      carbon electrode (GCE) was modified with lipase-nanoporous gold (NPG)
      biocomposite (denoted as lipase/NPG/GCE). Due to highly conductive, porous, and
      biocompatible three-dimensional structure, NPG is suitable for enzyme
      immobilization. In cyclic voltammetry experiments, the lipase/NPG/GCE
      bioelectrode displayed surface-confined reaction in a phosphate buffer solution.
      Linear responses were obtained for tributyrin concentrations ranging from 50 to
      250 mg dl(-1) and olive oil concentrations ranging from 10 to 200 mg dl(-1). The
      value of apparent Michaelis-Menten constant for tributyrin was 10.67 mg dl(-1)
      and the detection limit was 2.68 mg dl(-1). Further, the lipase/NPG/GCE
      bioelectrode had strong anti-interference ability against urea, glucose,
      cholesterol, and uric acid as well as a long shelf-life. For the detection of
      triglycerides in human serum, the values given by the lipase/NPG/GCE bioelectrode
      were in good agreement with those of an automatic biochemical analyzer. These
      properties along with a long self-life make the lipase/NPG/GCE bioelectrode an
      excellent choice for the construction of triglycerides biosensor.

PMID- 24121204
TI  - Decreased norepinephrine transporter availability in obesity: Positron Emission
      Tomography imaging with (S,S)-[(11)C]O-methylreboxetine.
AB  - OBJECTIVES: Noradrenergic dysfunction is implicated in obesity. The
      norepinephrine transporter (NET) regulates the synaptic availability of
      norepinephrine. However, NET availability has not been previously characterized
      in vivo in obese people using Positron Emission Tomography (PET) imaging. Here we
      report findings evaluating NET availability in individuals with obesity and
      matched lean (i.e., normal weight) comparison subjects. METHODS: Seventeen obese
      but otherwise healthy individuals with a mean+/-SD body mass index (BMI) of
      34.7+/-2.6 and 17 lean individuals with a mean+/-SD BMI of 23.1+/-1.4 were
      studied using a high-resolution research tomograph (HRRT) and (S,S)-[(11)C]O
      methylreboxetine ([(11)C]-MRB), a radioligand selective for the NET. The regional
      brain NET binding potential (BPND) was estimated by the multilinear reference
      tissue model 2 (MRTM2) with the occipital cortex as a reference region. BPND for
      regions of interest were obtained with the Automated Anatomic Labeling (AAL)
      template registered to individual's structural MR scans. RESULTS: Obese
      individuals had lower NET BPND values in the thalamus (p<0.038, 27% reduction)
      including within the pulvinar (p<0.083, 30% reduction), but not in the
      hypothalamus, locus coeruleus or the raphe nuclei, compared to lean individuals.
      When age was included as a covariate, the difference in NET BPND values remained
      significant in the thalamus (p<0.025) and pulvinar (p<0.042). CONCLUSIONS: These
      results indicate that NET availability is decreased in the thalamus, including
      the pulvinar, in obese individuals. These findings further support data
      indicating noradrenergic dysfunction in obesity and suggest impaired NE clearance
      in obesity.

PMID- 24121207
TI  - Assessment of genotoxicity of catecholics using impedimetric DNA-biosensor.
AB  - The potential toxicity of catecholics is a big concern, because the catechol
      derived semiquinone radical after the oxidation of catechol (CA) can donate an H
      atom to generate quinone, and during this process a superoxide anion radical may
      be produced. Considering the fact that catecholics are highly consumed in our
      daily life and some drugs also contain one or more CA moieties, we speculate that
      CA's toxicity might not be insurmountable. Therefore, finding approaches to
      investigate catecholics potential toxicity is of great significance. Here in, an
      electrochemical protocol for direct monitoring of genotoxicity of catecholics is
      described. CA encapsulated on MWCNTs (CA@MWCNT) through continuous cyclic
      voltammetric on the surface of pencil graphite electrode (PGE). Subsequently, a
      DNA functionalized biosensor (DNA/CA@MWCNT/PGE) was prepared and characterized
      for the detection and the investigation of DNA damage induced by radicals
      generated from catecholics. The change in the charge transfer resistance (Rct)
      after the incubation of the DNA biosensor in the damaging solution for a certain
      time was used as an indicator for DNA damage. Incubation of DNA-modified
      electrode with CA solution containing Cu(II), Cr(VI) and Fe(III) has been shown
      to result in oxidative damage to the DNA and change in the electrochemical
      properties. It was found that the presence of Cu(II), Cr(VI) and Fe(III) in
      solution caused damage to DNA. The inhibitory effect of glutathione and plumbagin
      on the CA-mediated DNA damage has also been investigated using the biosensor. The
      minimum concentration of the metal ions for CA induced DNA damage was
      investigated. Recognition of suitable matrixes for CA-mediated DNA damage can be
      assessed using proposed DNA biosensor. Such direct monitoring of the DNA damage
      holds great promise for designing new biosensors with modification of the
      biosensor with different damaging agents.

PMID- 24121208
TI  - Polymers effects on synthesis of AuNPs, and Au/Ag nanoalloys: indirectly
      generated AuNPs and versatile sensing applications including anti-leukemic agent.
AB  - Polymers either serve as shielding or capping agents to restrict the nanoparticle
      size. This study demonstrates the polymer depositions and their effects in
      synthesis and sharp stabilization of gold nanoparticles (AuNPs) and to develop
      gold/silver nanoalloys (Au/Ag nanoalloys). Effects of different polymers are
      tested to justify their role in synthesis and stability of phloroglucinol (PG)
      coated AuNPs and Au/Ag nanoalloys. Cationic and anionic i.e.
      [Polydiallyldimethylammonium](+) (PDDA), [Polyethyleneimine](+) (PEI),
      [Polystyrene sulfonate](2-) (PSS) and neutral polymer Polychlorotriflouroethylene
      (PCTFE) produce praiseworthy stable AuNPs and Au/Ag nanoalloy. To prove polymer
      effects characterization protocols including UV-vis, Fluorescence (PL), IR and
      AFM imaging are performed to fully investigate the mechanism and size
      characteristics of these nanoparticles/nanoalloys. In this study sharp size
      controlling/sheilding effects were observed particularly with cationic polymers
      simply through the favorable electrostatic interactions with the terminal ends of
      PG Potent/significant detection of doxorubicin (DOX, an antileukemic agent) via
      fluorescence resonance energy transfer (FRET) between PEI shielded AuNPs (AuNPEI)
      and DOX was achieved upto 10 pM level, while PDDA protected AuNPs facilitated the
      detection of ascorbic acid based on fluorescence enhancement effects in wide
      range (10-200 nM) and with detection limit of 200 pM. Similarly sensing
      performance of PEI stabilized Au/Ag nanoalloys on addition of halides (Cl(-), Br(
      ), I(-)) is evaluated through red shifted SPR along with continuous increase in
      absorbance and also through AFM. Moreover the addition of halide ions also helped
      the regeneration of AuNPs by taking away silver from the Au/Ag nanoalloys
      enabling their detections upto subnanomolar levels.

PMID- 24121209
TI  - An aptamer based wall-less LSPR array chip for label-free and high throughput
      detection of biomolecules.
AB  - Despite recent progress in localized surface plasmon resonance (LSPR) based bio
      sensing, it remains challenging to achieve sensitive and high throughput LSPR
      detection with facilities available in common laboratories. Here we developed a
      wall-less LSPR array chip for facile, label-free and high throughput detection of
      biomolecules using a normal microplate reader. The wall-less LSPR array chip was
      fabricated by immobilizing plasmonic nanoparticles (NPs) on a hydrophilic
      hydrophobic patterned glass slide, enabling high throughput detection. The wall
      less configuration simplifies chip fabrication and sample processing, and enables
      miniaturization to significantly reduce sample and reagent consumption. A double
      gold NPs enhanced system comprising of 13-nm-gold NPs conjugated to aptamer
      modified 39-nm-gold NPs on glass substrate was adopted to constitute competitive
      replacement assay for signal amplification in small molecule (i.e. ATP)
      detection. Upon enhancement, the detection sensitivity of ATP was augmented by 5
      orders of magnitude from 0.01 uM to 100 uM measured by the laboratory microplate
      reader. The wall-less LSPR sensor chip can be widely applied for miniaturized and
      high throughput detection of a variety of targets in biomedical applications and
      environmental monitoring using facilities available in common laboratories.

PMID- 24121210
TI  - Patient education in allogeneic hematopoietic cell transplant: what patients wish
      they had known about quality of life.
AB  - Quality of life (QOL) is increasingly recognized as an important clinical outcome
      of hematopoietic cell transplantation (HCT), but patient education is often
      overlooked. The aim of the current qualitative study was to examine education
      regarding post-HCT QOL from the patient's perspective. Allogeneic HCT recipients
      participated in one of four focus groups. Participants were asked to recall what
      they had been told about post-HCT QOL as they were preparing for transplant, how
      their QOL differed from what they expected and how to educate future patients
      about post-HCT QOL. Verbatim transcripts were coded for both a priori and
      emergent themes using content analysis. A total of 24 patients participated (54%
      female, mean age 51, range 23-73 years). Participants frequently expressed the
      desire for additional education regarding post-HCT QOL, particularly late
      complications. They noted that late complications were often unexpected, had a
      profound impact on their QOL and threatened their ongoing sense of recovery. They
      emphasized that the timing, content and format of education regarding QOL should
      be flexible to meet their diverse needs. Findings from the current study draw
      attention to the importance of patient education regarding post-HCT QOL as well
      as additional QOL research designed with patient education in mind. 

PMID- 24121211
TI  - Bone mineral deficits in recipients of hematopoietic cell transplantation: the
      impact of young age at transplant.
AB  - Low bone mineral density (BMD) has been reported in recipients of pediatric
      hematopoietic cell transplantation (HCT), but it is unclear whether age at HCT
      has a role. The objective of this cross-sectional study was to determine if
      patients treated with HCT before the age of 10 years have long-term BMD deficits
      compared with patients transplanted at an older age and with sibling controls.
      The study included 151 HCT recipients (87 males), age at study 24.7+/-8.6 years
      treated with HCT for hematologic malignancies at age 10.9+/-6.4 years, and 92
      healthy sibling controls (49 males), age at study 22.3+/-8.0 years. Dual-energy x
      ray absorptiometry was performed to measure BMD Z-scores for total body BMD
      (TBMD), lumbar spine BMD (LBMD) and femoral neck BMD (FNBMD, for subjects ?20
      years at study visit). Patients <10 years at HCT had significantly lower TBMD and
      FNBMD Z-scores (by 0.5 and 0.8 s.d., respectively) compared with controls
      (P=0.003 and P=0.0001, respectively) and patients >18 years at HCT (P=0.04 and
      P=0.004, respectively) at an average of 14 years after HCT. In conclusion, this
      study identified young age at transplant as an important risk factor for bone
      deficits in young adulthood, suggesting that efforts to reduce bone loss should
      focus on this patient population. 

PMID- 24121212
TI  - Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT
      recipients.
AB  - This study was aimed at finding predictors of invasive fungal infection (IFI)
      after pediatric allogeneic hematopoietic SCT (HSCT). All children who received
      allogeneic HSCT in the Wilhelmina Children's Hospital Utrecht between 2004 and
      2012 were included. HSCT data were prospectively collected. Patients were
      retrospectively classified into high- or low-risk groups for developing IFI using
      criteria based on available literature. Predictors for the occurrence of IFI were
      analyzed using Cox regression models. We used logistic regression models to
      analyze the association between other HSCT-related complications and IFI.
      Secondary outcomes were overall survival and treatment-related mortality (TRM).
      Two-hundred nine patients were included in the analysis; median age was 6.6
      years. The cumulative incidence of IFI was 12%. In patients classified as 'low
      risk' (n=75), only 5.3% developed IFI (odds ratio (OR): 0.325; P=0.047). In
      multivariate analysis, a predictor for the occurrence of IFI was an a priori
      determined HSCT TRM risk >20% (based on EBMT-risk score). Post-HSCT, the
      administration of high-dose steroids was associated with IFI (OR: 4.458;
      P=0.010). Patients who developed IFI showed an increased risk of TRM (OR: 3.773;
      P=0.004). These results confirm that risk group stratification should guide
      intensity of monitoring for IFI and use of antifungal prophylaxis. 

PMID- 24121213
TI  - Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in
      the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes.
AB  - Owing to ethnicity of the population, those best confirmed polymorphisms in the
      TLR (toll-like receptor)4 and NOD2 genes with significantly prognostic impact on
      allogeneic hematopoietic SCT (allo-HSCT) seem to be more applicable to Europeans
      and are nonpolymorphic in the Asian population. The influence of innate immunity
      gene polymorphisms on the outcomes of allo-HSCT in those populations has been
      questioned. We evaluated the influence of 10 candidate single nucleotide
      polymorphisms (SNPs) in the TLR1, TLR2, TLR3, TLR8 and TLR9 genes on the outcomes
      of allo-HSCT in a Chinese population including 138 pairs of patients and
      unrelated donors and a second cohort of 102 pairs of patients and HLA-identical
      sibling donors. We found that two tagSNPs in the TLR9 gene in the donor side,
      +1174 A/G (rs352139) and +1635 C/T (rs352140), influenced the risk of acute GVHD
      (aGVHD) and CMV reactivation. Furthermore, the presence of the susceptible
      haplotype (A-C) in donor may be an informative predicator of worse OS at 5 years
      compared with those with the G-C and G-T haplotypes (58% vs 82.9%, P=0.024). Our
      data suggested an unrecognized association between donor TLR9 tagSNPs and the
      risk of HSCT-related complications in a population without polymorphisms in the
      TLR4 and NOD2 genes. 

PMID- 24121214
TI  - Visualization of craniofacial development in the sox10: kaede transgenic
      zebrafish line using time-lapse confocal microscopy.
AB  - Vertebrate palatogenesis is a highly choreographed and complex developmental
      process, which involves migration of cranial neural crest (CNC) cells,
      convergence and extension of facial prominences, and maturation of the
      craniofacial skeleton. To study the contribution of the cranial neural crest to
      specific regions of the zebrafish palate a sox10: kaede transgenic zebrafish line
      was generated. Sox10 provides lineage restriction of the kaede reporter protein
      to the neural crest, thereby making the cell labeling a more precise process than
      traditional dye or reporter mRNA injection. Kaede is a photo-convertible protein
      that turns from green to red after photo activation and makes it possible to
      follow cells precisely. The sox10: kaede transgenic line was used to perform
      lineage analysis to delineate CNC cell populations that give rise to maxillary
      versus mandibular elements and illustrate homology of facial prominences to
      amniotes. This protocol describes the steps to generate a live time-lapse video
      of a sox10: kaede zebrafish embryo. Development of the ethmoid plate will serve
      as a practical example. This protocol can be applied to making a time-lapse
      confocal recording of any kaede or similar photoconvertible reporter protein in
      transgenic zebrafish. Furthermore, it can be used to capture not only normal, but
      also abnormal development of craniofacial structures in the zebrafish mutants. 

PMID- 24121215
TI  - Propofol limits microglial activation after experimental brain trauma through
      inhibition of nicotinamide adenine dinucleotide phosphate oxidase.
AB  - BACKGROUND: Microglial activation is implicated in delayed tissue damage after
      traumatic brain injury (TBI). Activation of microglia causes up-regulation of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, with the release of
      reactive oxygen species and cytotoxicity. Propofol appears to have
      antiinflammatory actions. The authors evaluated the neuroprotective effects of
      propofol after TBI and examined in vivo and in vitro whether such actions
      reflected modulation of NADPH oxidase. METHODS: Adult male rats were subjected to
      moderate lateral fluid percussion TBI. Effect of propofol on brain microglial
      activation and functional recovery was assessed up to 28 days postinjury. By
      using primary microglial and BV2 cell cultures, the authors examined propofol
      modulation of lipopolysaccharide and interferon-gamma-induced microglial
      reactivity and neurotoxicity. RESULTS: Propofol improved cognitive recovery after
      TBI in novel object recognition test (48 +/- 6% for propofol [n = 15] vs. 30 +/-
      4% for isoflurane [n = 14]; P = 0.005). The functional improvement with propofol
      was associated with limited microglial activation and decreased cortical lesion
      volume and neuronal loss. Propofol also attenuated lipopolysaccharide- and
      interferon-gamma-induced microglial activation in vitro, with reduced expression
      of inducible nitric oxide synthase, nitric oxide, tumor necrosis factor-alpha,
      interlukin-1beta, reactive oxygen species, and NADPH oxidase. Microglial-induced
      neurotoxicity in vitro was also markedly reduced by propofol. The protective
      effect of propofol was attenuated when the NADPH oxidase subunit p22 was knocked
      down by small interfering RNA. Moreover, propofol reduced the expression of p22
      and gp91, two key components of NADPH oxidase, after TBI. CONCLUSION: The
      neuroprotective effects of propofol after TBI appear to be mediated, in part,
      through the inhibition of NADPH oxidase.

PMID- 24121216
TI  - Increased risk of awareness under anesthesia: an issue of consciousness or of
      memory?

PMID- 24121217
TI  - [Cellular and intracellular transport of vitamin C. The physiologic aspects].
AB  - Vitamin C requirement is satisfied by natural sources and vitamin C supplements
      in the ordinary human diet. The two major forms of vitamin C in the diet are L
      ascorbic acid and L-dehydroascorbic acid. Both ascorbate and dehydroascorbate are
      absorbed along the entire length of the human intestine. The reduced form, L
      ascorbic acid is imported by an active mechanism, requiring two sodium-dependent
      vitamin C transporters (SVCT1 and SVCT2). The transport of the oxidized form,
      dehydroascorbate is mediated by glucose transporters GLUT1, GLUT3 and possibly
      GLUT4. Initial rate of uptake of both ascorbate and dehydroascorbate is saturable
      with increasing external substrate concentration. Vitamin C plasma concentrations
      are tightly controlled when the vitamin is taken orally. It has two simple
      reasons, on the one hand, the capacity of the transporters is limited, on the
      other hand the two Na+-dependent transporters can be down-regulated by an
      elevated level of ascorbate.

PMID- 24121218
TI  - [Advantages of ramipril/amlodipin fixed combination therapy. When should we use
      it?].
AB  - Hypertension is one of the most frequent chronic disease in Hungary and one of
      the most important cardiovascular risk factor. Treatment of blood pressure to
      target value lowers significantly the risk of coronary artery disease, stroke and
      chronic renal disease as well as it decreases mortality. Blood pressure control
      has a great importance in high risk patients. In addition to life style changes,
      drug treatment plays an essential role in the management of hypertensive
      patients. The complexity of drug regimen, characteristics of drug class, age and
      gender are all exert impacts on patient adherence. Antihypertensive drugs should
      preferably have metabolically neutral properties and cardiovascular protective
      effects. Ramipril/amlodipine fixed combination meets these criteria and adherence
      of patients is favorable.

PMID- 24121219
TI  - [Treatment outcome in primary testicular non-Hodgkin lymphoma].
AB  - INTRODUCTION: Primary testicular lymphoma constitutes a rare subgroup among
      extranodal non-Hodgkin's lymphomas. Because of its aggressive clinical behaviour
      due to high grade histological features developing mainly in older population,
      patients with this disease usually have a poor prognosis. Orchidectomy followed
      by combination immunochemotherapy is a traditional treatment method with a rather
      inferior outcome. AIM: In this retrospective survey the authors analysed the
      clinical presentation, pathological features and treatment results of patients
      with primary testicular lymphoma diagnosed and treated in their haematology
      centre between 2000-2012 METHOD: During this period 334 patients with aggressive
      non-Hodgkin's lymphomas were treated, of whom 8 patients (2.39%; age between 23
      and 86 years; median, 60 years) underwent semicastration for primary testicular
      lymphoma (7 patients had diffuse, large B-cell lymphoma and one patient had
      Burkitt-like lymphoma). According to the Ann Arbor staging system a limited stage
      I-IIE was diagnosed in 7 patients and advanced stage was found in one patient.
      All but one patients were treated with rituximab added to CHOP regimen (6 or 8
      cycles in every 21 or 28 days), whereas one patient received radiotherapy only.
      Central nervous system intrathecal prophylaxis was used in one case and no
      preventive irradiation of the contralateral testis was used. RESULTS: With a
      median follow-up of 50 months complete remission was observed in 7 patients.
      However, two patients died (one due to progression and one in remission from
      pulmonary solid tumour). Complete remission rate proved to be 87.5%, disease-free
      survival was between 13 and 152 months (median 38 months) and overall survival
      rates were between 17 and 156 months (median 43 months). The 5-year disease-free
      and overall survival rates were 37.5 %. CONCLUSIONS: The relatively favourable
      treatment outcome could be mainly explained by the high number of patients with
      early-stage of the disease, early surgical removal of testicular lymphomas and
      the use if immunochemotherapy. This therapeutic regimen was effective to prevent
      localized and distant relapses. Despite omission of regular prophylaxis of the
      central nervous system, no relapse was detected.

PMID- 24121220
TI  - [Effectiveness of pentoxifylline and of bio-electromagnetic therapy in lower limb
      obliterative arterial disease].
AB  - INTRODUCTION: There are limited therapeutic options to improve microcirculation.
      AIM: The question of the study was to investigate any potential beneficial effect
      of bio-electro-magnetic-regulation therapy on microcirculation in patients
      suffering from obliterative peripheral arterial disease including the circulation
      of lower extremities, as well as intermittent claudication. METHOD: Thirty
      patients suffering from obliterative peripheral arterial disease (Fontaine IIa
      and IIb) were recruited. The first step of the study was to determine the pain
      free and maximal walking distance with a treadmill unit. After the placebo period
      patients received 8 and 20 minutes bio-electro-magnetic-regulation treatment 16
      times. After the treatment the pain free and maximal walking distance were
      measured again. In the second stage of the study the patients were treated by
      pentoxifylline infusions. RESULTS: Bio-electro-magnetic-regulation treatment
      increased the pain free period by 57.4% (p = 0.005) and the maximal walking
      distance by 36.6% (p = 0.042). The two forms of therapy together increased the
      pain free and maximal walking distance by 81.9% and by 84.0%, respectively. The
      combined therapy was very effective in contrast to placebo and bio-electro
      magnetic-regulation treatment (p = 0.000373 and p = 0.00741, respectively).
      CONCLUSIONS: The bio-electro-magnetic-regulation therapy mainly affected the
      microvessels and pentoxifylline therapy rather had beneficial effects on
      hemorheology. The clinical effectiveness of combined therapy was good or
      excellent in 70% of patients.

PMID- 24121221
TI  - [Medical history references of the African journeys of Laszlo Magyar (1818
      1864)].

PMID- 24121222
TI  - [Under the shadow of his elder brother? Appointment of Janos Imre Orsos 1889
      1959) to lead the Department of Dermatology at Debrecen University in 1940].

PMID- 24121224
TI  - Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS
      imaging system.
AB  - Measurement of brain activity in multiple areas simultaneously by minimally
      invasive methods contributes to the study of neuroscience and development of
      brain machine interfaces. However, this requires compact wearable instruments
      that do not inhibit natural movements. Application of optical potentiometry with
      voltage-sensitive fluorescent dye using an implantable image sensor is also
      useful. However, the increasing number of leads required for the multiple wired
      sensors to measure larger domains inhibits natural behavior. For imaging broad
      areas by numerous sensors without excessive wiring, a web-like sensor that can
      wrap the brain was developed. Kaleidoscopic potentiometry is possible using the
      imaging system with concatenated sensors by changing the alignment of the
      sensors. This paper describes organization of the system, evaluation of the
      system by a fluorescence imaging, and finally, functional brain fluorescence
      plurimetry by the sensor. The recorded data in rat somatosensory cortex using the
      developed multiple-area imaging system compared well with electrophysiology
      results. 

PMID- 24121225
TI  - A highly selective sensor of cysteine with tunable sensitivity and detection
      window based on dual-emission Ag nanoclusters.
AB  - An effective dual-emission fluorescent Ag nanoclusters (NCs)-based probe have
      been constructed for rapid and selective detection of cysteine (Cys) with tunable
      sensitivity. Electrostatically induced reversible phase transfer method is
      employed to synthesize Ag nanoclusters with tunable emission intensity at 430 nm
      and 630 nm by controlling molar ratio between Ag and glutathione. The
      fluorescence of the Ag nanoclusters could be selectively quenched in the presence
      of Cys with a detection limit as low as 10nM. Good linear correlations are
      obtained over the concentration range from 0.5 to 55 MUM (quenched emission at
      630 nm), 55 to 120 MUM and 120 to 220 MUM (enhanced emission at 555 nm) and 120
      to 200 MUM (quenched emission at 430 nm), respectively. The long-wavelength
      emission of the Ag nanoclusters can avoid the interference of the
      autofluorescence of the biosystems, which facilitated their applications in
      monitoring Cys in urine.

PMID- 24121226
TI  - Label-free turn-on fluorescent detection of melamine based on the anti-quenching
      ability of Hg 2+ to gold nanoclusters.
AB  - In this work, we proposed a facile, environmentally friendly and cost-effective
      assay for melamine with BSA-stabilized gold nanoclusters (AuNCs) as a
      fluorescence reader. Melamine, which has a multi-nitrogen heterocyclic ring, is
      prone to coordinate with Hg(2+). This property causes the anti-quenching ability
      of Hg(2+) to AuNCs through decreasing the metallophilic interaction between
      Hg(2+) and Au(+). By this method, detection limit down to 0.15 uM is obtained,
      which is approximately 130 times lower than that of the US food and Drug
      Administration estimated melamine safety limit of 20 uM. Furthermore, several
      real samples spiked with melamine, including raw milk and milk powder, are
      analyzed using the sensing system with excellent recoveries. This gold
      nanocluster-based fluorescent method could find applications in highly sensitive
      detection of melamine in real samples.

PMID- 24121227
TI  - Photopatterning of self assembled monolayers on oxide surfaces for the selective
      attachment of biomolecules.
AB  - The immobilization of functional biomolecules to surfaces is a critical process
      for the development of biosensors for disease diagnostics. In this work we report
      the patterned attachment of single chain fragment variable (scFv) antibodies to
      the surface of metal oxides by the photodeprotection of self-assembled
      monolayers, using near-UV light. The photodeprotection step alters the
      functionality at the surface; revealing amino groups that are utilized to bind
      biomolecules in the exposed regions of the substrate only. The patterned
      antibodies are used for the detection of specific disease biomarker proteins in
      buffer and in complex samples such as human serum. 

PMID- 24121229
TI  - Mesoscopic non-equilibrium thermodynamic analysis of molecular motors.
AB  - We show that the kinetics of a molecular motor fueled by ATP and operating
      between a deactivated and an activated state can be derived from the principles
      of non-equilibrium thermodynamics applied to the mesoscopic domain. The
      activation by ATP, the possible slip of the motor, as well as the forward
      stepping carrying a load are viewed as slow diffusion along a reaction
      coordinate. Local equilibrium is assumed in the reaction coordinate spaces,
      making it possible to derive the non-equilibrium thermodynamic description. Using
      this scheme, we find expressions for the velocity of the motor, in terms of the
      driving force along the spacial coordinate, and for the chemical reaction that
      brings about activation, in terms of the chemical potentials of the reactants and
      products which maintain the cycle. The second law efficiency is defined, and the
      velocity corresponding to maximum power is obtained for myosin movement on actin.
      Experimental results fitting with the description are reviewed, giving a maximum
      efficiency of 0.45 at a myosin headgroup velocity of 5 * 10(-7) m s(-1). The
      formalism allows the introduction and test of meso-level models, which may be
      needed to explain experiments. 

PMID- 24121228
TI  - Development of spatial representation of numbers: a study of the SNARC effect in
      Chinese children.
AB  - Using the standard parity judgment task, this study investigated the development
      of numerical-spatial representation. Participants were 314 healthy right-handed
      Chinese children (from kindergarteners to sixth graders) and adults. The results
      revealed that all age groups showed a significant (or marginally significant in
      the case of first graders) SNARC (spatial-numerical association of response
      codes) effect, indicating that Chinese children as young as kindergarteners
      already had developed automatic spatial representations of numbers (or the mental
      number line). Surprisingly, however, the size of the SNARC effect did not show
      much developmental change. These results are discussed in the context of the
      literature on spatial representations of numbers and on cross-cultural
      differences in early development of number cognition. 

PMID- 24121230
TI  - Narrative responses as an aid to understanding the presentation of maltreated
      children who meet criteria for autistic spectrum disorder and reactive attachment
      disorder: a case series study.
AB  - This paper offers research case studies of four severely maltreated children who
      had received a diagnosis of autistic spectrum disorder. A range of measures were
      employed to explore the children's psychological and emotional functioning,
      including Theory of Mind assessment (Sally-Anne Test), attachment measures (Story
      Stems Assessment Profile and Relationship Problems Questionnaire), along with
      measures to assess general psychological and emotional well-being. Contrary to
      the diagnosis, the children did not reveal a theory of mind deficit. However,
      they did indicate a profile of difficulties in mentalisation on the Story Stems.
      The findings are discussed in terms of the extent to which mentalisation and
      theory of mind are influenced by situational factors, especially the anxiety
      evoked by the Story Stem attachment scenarios. Clinical implications regarding
      mentalisation as a state vs. trait phenomenon are discussed. 

PMID- 24121231
TI  - Structure and RNA-binding properties of the Not1-Not2-Not5 module of the yeast
      Ccr4-Not complex.
AB  - The Ccr4-Not complex is involved in several aspects of gene expression, including
      mRNA decay, translational repression and transcription. We determined the 2.8-A
      resolution crystal structure of a 120-kDa core complex of the Saccharomyces
      cerevisiae Not module comprising the C-terminal arm of Not1, Not2 and Not5. Not1
      is a HEAT-repeat scaffold. Not2 and Not5 have extended regions that wrap around
      Not1 and around their globular domains, the Not boxes. The Not boxes resemble Sm
      folds and interact with each other with a noncanonical dimerization surface.
      Disruption of the interactions within the ternary complex has severe effects on
      growth in vivo. The ternary complex forms a composite surface that binds poly(U)
      RNA in vitro, with a site at the Not5 Not box. The results suggest that the Not
      module forms a versatile platform for macromolecular interactions. 

PMID- 24121233
TI  - Synthesis and antiproliferative activity of benzofuran-based analogs of
      cercosporamide against non-small cell lung cancer cell lines.
AB  - A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened
      in vitro for their antiproliferative activity against two human NSCLC cell lines
      (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented
      a structural analogy with the west part of cercosporamide, a natural product of
      biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic
      activities at micromolar concentrations (IC50 < 9.3 MUM) and compounds 13, 18 and
      32 displayed moderate IC50 values (25-40 MUM).

PMID- 24121232
TI  - Structure and assembly of the NOT module of the human CCR4-NOT complex.
AB  - The CCR4-NOT deadenylase complex is a master regulator of translation and mRNA
      stability. Its NOT module orchestrates recruitment of the catalytic subunits to
      target mRNAs. We report the crystal structure of the human NOT module formed by
      the CNOT1, CNOT2 and CNOT3 C-terminal (-C) regions. CNOT1-C provides a rigid
      scaffold consisting of two perpendicular stacks of HEAT-like repeats. CNOT2-C and
      CNOT3-C heterodimerize through their SH3-like NOT-box domains. The heterodimer is
      stabilized and tightly anchored to the surface of CNOT1 through an unexpected
      intertwined arrangement of peptide regions lacking defined secondary structure.
      These assembly peptides mold onto their respective binding surfaces and form
      extensive interfaces. Mutagenesis of individual interfaces and perturbation of
      endogenous protein ratios cause defects in complex assembly and mRNA decay. Our
      studies provide a structural framework for understanding the recruitment of the
      CCR4-NOT complex to mRNA targets. 

PMID- 24121234
TI  - Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment
      of cancer.
AB  - To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series
      of new lapatinib analogs were designed and synthesized. Compared with lapatinib,
      L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo
      efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI
      N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing
      significant loss of body weight. And the inhibition rates of lapatinib in the two
      xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies
      revealed that the potent in vivo activities of L-2 may be mainly attributed to
      its superior aqueous solubility and oral bioavailability. In addition, a high
      yielding one-pot procedure was developed for the synthesis of lapatinib and its
      analogs.

PMID- 24121235
TI  - Platinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane derivatives as
      carrier ligands and 3-hydroxycyclobutane-1,1-dicarboxylate as a leaving group:
      potent cytotoxicity and DNA binding ability.
AB  - A series of novel platinum(II) complexes with N-monoalkyl 1R,2R
      diaminocyclohexane derivatives and 3-hydroxycyclobutane-1,1-dicarboxylate as
      ligands were designed and synthesized. The cytotoxicity study revealed that most
      of synthesized complexes showed moderate to potent activity against all four
      tested tumor cell lines. Particularly, 1d showed much higher cytotoxic activity
      than carboplatin and oxaliplatin against MCF-7 and A549 cell lines. Due to the
      employment of N-monoalkyl 1R,2R-diaminocyclohexane derivatives and 3
      hydroxycyclobutane-1,1-dicarboxylate as ligands, the calculated log P values of
      the complexes are around 1, suggesting a good balance of the lipophilicity and
      hydrophilicity. The aqueous solubility of 1d is also improved, reaches 24.6
      mg/mL. Furthermore, both docking study and agarose gel electrophoresis have
      confirmed the DNA-binding ability of 1d.

PMID- 24121236
TI  - New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine
      series: synthesis, growth inhibitory activity on human tumor cell lines and non
      tumor cells, effects on cell cycle and on programmed cell death.
AB  - New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines
      were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using
      copper (C-O) or palladium (C-N) catalyzed couplings, respectively, of the 7
      bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or
      methoxy phenols and anilines. The compounds obtained were evaluated for their
      growth inhibitory activity on the human tumor cell lines MCF-7 (breast
      adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma),
      HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active
      compounds, a di(hetero)arylether with a methoxy group in the meta position
      relative to the ether function and two di(hetero)arylamines with a methoxy group
      either in the ortho or in the meta position relative to the NH, were further
      tested at their GI50 concentrations on NCI-H460 cells causing pronounced
      alterations in the cell cycle profile and a strong and significant increase in
      the programmed death of these cells. The fluorinated and the other methoxylated
      compounds did not show important activity, presenting high GI50 values in all the
      cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed
      using porcine liver primary cells (PLP2), established by some of us. Results
      showed that one of the most active compounds was not toxic to the non-tumor cells
      at their GI50 concentrations showing to be the most promising as antitumoral.

PMID- 24121237
TI  - "Green" electronics: biodegradable and biocompatible materials and devices for
      sustainable future.
AB  - "Green" electronics represents not only a novel scientific term but also an
      emerging area of research aimed at identifying compounds of natural origin and
      establishing economically efficient routes for the production of synthetic
      materials that have applicability in environmentally safe (biodegradable) and/or
      biocompatible devices. The ultimate goal of this research is to create paths for
      the production of human- and environmentally friendly electronics in general and
      the integration of such electronic circuits with living tissue in particular.
      Researching into the emerging class of "green" electronics may help fulfill not
      only the original promise of organic electronics that is to deliver low-cost and
      energy efficient materials and devices but also achieve unimaginable
      functionalities for electronics, for example benign integration into life and
      environment. This Review will highlight recent research advancements in this
      emerging group of materials and their integration in unconventional organic
      electronic devices. 

PMID- 24121238
TI  - Effect of dosing time on the ammonium nitrogen disinhibition in autothermal
      thermophilic aerobic digestion for sewage sludge by chemical precipitation.
AB  - Magnesium ammonium phosphate (MAP) precipitation was introduced to remove
      ammonium nitrogen (NH4(+)-N) in autothermal thermophilic aerobic digestion (ATAD)
      in this study. The dosing time of MgCl2 . 6H2O and NaH2PO4 . 2H2O will influence
      the removal efficiency of ammonium nitrogen greatly, and the time interval of
      2nd, 7th, 12th day were chosen in ATAD process. The lowest NH4(+)-N concentration
      was found in the 2nd day dosing digester, and 38.37% of VS removal rate was
      obtained after 12 days digestion, which achieved stabilization 9 days earlier
      than the non-dosing digester. It revealed that removal of ammonium nitrogen could
      accelerate the sludge stabilization process. Meanwhile, 49.30% of VS removal rate
      was found in the 2nd day dosing digester in the 21st day, much higher than that
      in the non-dosing digester, the 7th day dosing digester, and the 12th day dosing
      digester, with the corresponding value of 38.37%, 38.38% and 37.04%,
      respectively.

PMID- 24121239
TI  - Biogas production from wheat straw and manure--impact of pretreatment and process
      operating parameters.
AB  - Non-treated or steam-exploded straw in co-digestion with cattle manure was
      evaluated as a substrate for biogas production compared with manure as the sole
      substrate. All digestions were performed in laboratory-scale CSTR reactors (5L)
      operating with an organic loading late of approximately 2.8 g VS/L/day,
      independent of substrate mixture. The hydraulic retention was 25 days and an
      operating temperature of 37, 44 or 52 degrees C. The co-digestion with steam
      exploded straw and manure was evaluated with two different mixtures, with
      different proportion. The results showed stable performance but low methane
      yields (0.13-0.21 N L CH4/kg VS) for both manure alone and in co-digestion with
      the straw. Straw appeared to give similar yield as manure and steam-explosion
      treatment of the straw did not increase gas yields. Furthermore, there were only
      slight differences at the different operating temperatures.

PMID- 24121240
TI  - Secondary amines as switchable solvents for lipid extraction from non-broken
      microalgae.
AB  - Lipids from algal biomass may provide renewable fuel and chemical feedstock in
      large quantities. The energy intensity of drying and milling of algae prior to
      extraction and of solvent recovery afterwards is a major obstacle. The objective
      is to use switchable solvents to extract oil directly from wet microalgae
      slurries without the need for drying and milling, and subsequently recover the
      extracted oil and solvent by simple phase splitting, using CO2 as trigger. In
      this work secondary amine solvents were investigated for lipids extraction,
      polarity switching and phase splitting ability upon contacting with CO2. For
      strain Desmodesmus sp. extraction yields from the wet algal slurries, with and
      without cell disruption, were comparable with Bligh & Dyer method yields. Oil and
      solvent recovery via phase separation was realized by CO2 induced phase
      splitting, making secondary amines a candidate for further development of an
      energy efficient lipid extraction technology for non-broken microalgae. 

PMID- 24121241
TI  - Establishing and evaluating wrist cutpoints for the GENEActiv accelerometer in
      youth.
AB  - PURPOSE: This study aimed to establish physical activity (PA) intensity cutpoints
      for a wrist-mounted GENEActiv accelerometer (ACC) in elementary school-age
      children. A second purpose was to apply cutpoints to a free-living sample and
      examine the duration of PA based on continuous 1-s epochs. METHODS: Metabolic and
      ACC data were collected during nine typical activities in 24 children age 6-11
      yr. Measured VO2 values were divided by Schofield-estimated resting values to
      determine METs. ACC data were collected at 75 Hz, band pass filtered, and
      averaged over each 1-s interval. Receiver operator characteristic curves were
      used to establish cutpoints at sedentary (<= 1.5 METs), light (1.6-2.99 METs),
      moderate (3.0-5.99 METs), and vigorous (>= 6 METs) activities. These cutpoints
      were applied to a free-living independent data set to quantify the amount of
      moderate-vigorous PA (MVPA) and to examine how bout length (1, 2, 3, 5, 10, 15,
      and 60 s) affected the accumulation of MVPA. RESULTS: Receiver operator
      characteristic yielded areas under the curve of 0.956, 0.946, and 0.940 for
      sedentary, moderate, and vigorous intensities, respectively. Cutpoints for
      sedentary, moderate, and vigorous intensities were 0.190 g, 0.314 g, and 0.998 g,
      respectively. Intensity classification accuracies ranged from 27.6% (light) to
      88.7% (vigorous) when cutpoints were applied to the calibration data. When
      applied to free-living data (n = 47 children age 6-11 yr), estimated daily MVPA
      was 308 min and decreased to 14.3 min when only including 1-min periods of
      continuous MVPA. CONCLUSIONS: Cutpoints that quantify movements associated with
      moderate-vigorous intensity, when applied to a laboratory protocol, result in
      large amounts of accumulated MVPA using the 1-s epoch compared to prior studies,
      highlighting the need for representative calibration activities and free-living
      validation of cutpoints and epoch length selection.

PMID- 24121242
TI  - Talking yourself out of exhaustion: the effects of self-talk on endurance
      performance.
AB  - PURPOSE: The psychobiological model of endurance performance proposes that the
      perception of effort is the ultimate determinant of endurance performance.
      Therefore, any physiological or psychological factor affecting the perception of
      effort will affect endurance performance. Accordingly, this novel study
      investigated the effects of a frequently used psychological strategy,
      motivational self-talk (ST), on RPE and endurance performance. METHODS: In a
      randomized between-group pretest-posttest design, 24 participants (mean +/- SD
      age = 24.6 +/- 7.5 yr, VO2max = 52.3 +/- 8.7 mL.kg.min) performed two constant
      load (80% peak power output) cycling time-to-exhaustion (TTE) tests, punctuated
      by a 2-wk ST intervention or a control phase. RESULTS: A group (ST vs Control) *
      test (pretest vs posttest) mixed-model ANOVA revealed that ST significantly
      enhanced TTE test from pretest to posttest (637 +/- 210 vs 750 +/- 295 s, P <
      0.05) with no change in the control group (486 +/- 157 vs 474 +/- 169 s).
      Moreover, a group * test * isotime (0%, 50%, and 100%) mixed-model ANOVA revealed
      a significant interaction for RPE, with follow-up tests showing that motivational
      self-talk significantly reduced RPE at 50% isotime (7.3 +/- 0.6 vs 6.4 +/- 0.8, P
      < 0.05), with no significant difference in the control group (6.9 +/- 1.9 vs 7.0
      +/- 1.7). CONCLUSIONS: This study is the first to demonstrate that ST
      significantly reduces RPE and enhances endurance performance. The findings
      support the psychobiological model of endurance performance and illustrate that
      psychobiological interventions designed to specifically target favorable changes
      in the perception of effort are beneficial to endurance performance.
      Consequently, this psychobiological model offers an important and novel
      perspective for future research investigations.

PMID- 24121243
TI  - Home-based active video games to promote weight loss during the postpartum
      period.
AB  - PURPOSE: Weight retention during the postpartum period is critical for the later
      development of obesity in women. Traditional physical activity is frequently
      discontinued because of incompatibility with mothers' agenda (i.e., baby care).
      In the present study, active video games (AVG) are proposed for postpartum women
      to improve their body composition. METHODS: Thirty-four postpartum women (body
      mass index = 24.5 +/- 3.4 kg.m) were randomized to an AVG group or a control
      group. Subjects assigned to the AVG group were given a Wii Nintendo console with
      the game Wii Fit Plus for 40 d. The two groups were tested for weight, body mass
      index, body fat mass, waist and hip circumferences, and other anthropometric
      parameters. Physical fitness, energy expenditure, energy intake, and adverse
      events were also investigated. RESULTS: The AVG group lost more weight than the
      control group (-2.2 +/- 0.9 vs. -0.5 +/- 0.7 kg, P < 0.001). They also exhibited
      more important reductions of BMI, waist and hip circumferences, and body fat (P <
      0.05). During the 40-d period, subjects expended an estimated 4682 +/- 2874 kcal
      just by playing AVG. Daily energy intake was reduced by 206 +/- 559 kcal. There
      were significant positive correlations between playing frequency, total playing
      time, total energy expenditure during the 40-d period, and decrease in daily
      energy intake respectively, and weight loss (P < 0.05). Playing time data
      suggested no conflict with baby care activities. CONCLUSIONS: AVGs could
      represent an interesting spare physical activity for postpartum women. In the
      present study, these games promoted physical activity, induced a reduction of
      energy intake, and subsequently minimized weight retention.

PMID- 24121244
TI  - Neuromotor control of gluteal muscles in runners with achilles tendinopathy.
AB  - PURPOSE: The purpose of this study was to compare the neuromotor control of the
      gluteus medius (GMED) and gluteus maximus (GMAX) muscles in runners with Achilles
      tendinopathy to that of healthy controls. METHODS: Fourteen male runners with
      Achilles tendinopathy and 19 healthy male runners (control) ran overground while
      EMG of GMED and GMAX was recorded. Three temporal variables were identified via
      visual inspection of EMG data: (i) onset of muscle activity (onset), (ii) offset
      of muscle activity (offset), and (iii) duration of muscle activity (duration). A
      multivariate analysis of covariance with between-subject factor of group
      (Achilles tendinopathy, control) and variables of onset, offset, and duration was
      performed for each muscle. Age, weight, and height were included as covariates,
      and alpha level was set at 0.05. RESULTS: The Achilles tendinopathy group
      demonstrated a delay in the activation of the GMED relative to heel strike (P <
      0.001) and a shorter duration of activation (P < 0.001) compared to that of the
      control group. GMED offset time relative to heel strike was not different between
      the groups (P = 0.063). For GMAX, the Achilles tendinopathy group demonstrated a
      delay in its onset (P = 0.008), a shorter duration of activation (P = 0.002), and
      earlier offset (P < 0.001) compared to the control group. CONCLUSIONS: This study
      provides preliminary evidence of altered neuromotor control of the GMED and GMAX
      muscles in male runners with Achilles tendinopathy. Although further prospective
      studies are required to discern the causal nature of this relationship, this
      study highlights the importance of considering neuromotor control of the gluteal
      muscles in the assessment and management of patients with Achilles tendinopathy.

PMID- 24121245
TI  - Influence of tibial shock feedback training on impact loading and running
      economy.
AB  - PURPOSE: The purpose of this study was to determine whether real-time feedback
      (RTF) training would reduce impact loading variables previously linked with
      tibial stress fracture risk and whether these adaptations would influence running
      economy. METHODS: Twenty-two male runners were randomly assigned to RTF (n = 12)
      and control (n = 10) groups. The RTF group received feedback based on their peak
      tibial axial accelerations (PTA) during six 20-min treadmill runs for 3 wk,
      whereas the control group adhered to the same training but without feedback.
      Unilateral three-dimensional kinematic and kinetic analysis and running economy
      measurements were conducted before, after, and at 1 month posttraining. RESULTS:
      The RTF group had significant reductions (P < 0.01) in PTA and average and
      instantaneous vertical force loading rates after training as compared with no
      changes in the control group. These modifications in impact loads were only
      maintained in PTA 1 month after the training. A significant increase (P = 0.0033)
      in ankle plantarflexion at initial contact and a significant change (P = 0.030)
      in foot strike pattern from a rearfoot to midfoot strike pattern and a
      significant decrease (P = 0.008) in heel vertical velocity at initial contact
      appeared to be the primary mechanical strategies adopted by runners to reduce
      impact loading after RTF training. Despite these gait adaptations, running
      economy was unaffected. CONCLUSIONS: The results of this study suggest that gait
      retraining using RTF is an effective means of eliciting reductions in impact
      loading without negatively affecting running economy. However, with loading rate
      reductions not being maintained 1 month posttraining, further research is
      required to determine how these reductions in impact severity can be retained
      long term.

PMID- 24121246
TI  - Injuries in children with extra physical education in primary schools.
AB  - PURPOSE: (1) Examine the influence of extra physical education (EPE) on the
      number of musculoskeletal injuries in public schools accounting for organized
      sports participation (OSP) outside school. (2) Examine the major injury subgroup:
      growth-related overuse (GRO) through the overuse-related injury group. METHODS: A
      longitudinal controlled school-based study among Danish public schools. At
      baseline, 1216 children participated age 6.2-12.4 yr. Six schools (701 children)
      with EPE and four control schools (515 children) were followed up with weekly
      automated mobile phone text messages for information on musculoskeletal problems
      and OSP. Health care personnel diagnosed the children according to the World
      Health Organization's International Classification of Diseases, Tenth Revision.
      Data were analyzed using a two-part zero-inflated negative binomial (ZINB)
      regression model. RESULTS: School type had no influence on the odds of sustaining
      an injury but increased the probability of sustaining a higher injury count for
      children with injuries, with total injuries by a factor of 1.29 (95% confidence
      interval [CI] = 1.07-1.56), overuse by a factor of 1.29 (95% CI = 1.06-1.55), and
      GRO by a factor of 1.38 (95% CI = 1.02-1.80). Weekly mean OSP decreased the odds
      of belonging to the group of children with no injuries, by a factor of 0.29 (95%
      CI = 0.14-0.58), 0.26 (95% CI = 0.14-0.48), and 0.17 (95% CI = 0.06-0.52) for
      total, overuse, and GRO, respectively. OSP also increased the probability of
      sustaining a higher injury count for children with injuries by a factor of 1.11
      (95% CI = 1.02-1.22), 1.10 (95% CI = 1.00-1.22), and 1.14 (95% CI = 1.00-1.30),
      respectively. CONCLUSIONS: Children enrolled in EPE schools with high OSP have
      the highest odds of injury and a high probability of sustaining a higher injury
      count compared to their peers at schools with normal PE. Special attention should
      be assigned to these children during compulsory PE.

PMID- 24121247
TI  - Tracking of physical activity from early childhood through youth into adulthood.
AB  - PURPOSE: The aim of the study was to investigate the tracking of physical
      activity (PA) from preschool age to adulthood in six age cohorts of males and
      females. METHODS: A random sample of 3596 boys and girls age 3-18 yr participated
      in the Cardiovascular Risks in Young Finns Study in 1980. The follow-up
      measurements were repeated in 1986, 1992, 2001, and 2007. The PA was measured by
      mother's report in 3- and 6-yr-olds and self-report in 9-yr-olds and older.
      Tracking of PA was analyzed using the Spearman rank-order correlation and a
      simplex model. RESULTS: Mother-reported PA at age 3 and 6 yr significantly
      predicted self-reported PA in youth and in young adulthood, and there was a
      significant indirect effect of mother report on adult PA 2007 in males. Simplex
      models that fitted the data very well produced higher stability coefficients than
      the Spearman rank-order correlations showing moderate or high tracking. The
      tracking was higher in males than that in females. CONCLUSION: This study has
      shown that physically active lifestyle starts to develop very early in childhood
      and that the stability of PA is moderate or high along the life course from youth
      to adulthood.

PMID- 24121248
TI  - Prospective study of sedentary behavior, risk of depression, and cognitive
      impairment.
AB  - INTRODUCTION: Modern-day lifestyles are characterized by large amounts of
      prolonged sedentary activities, which may pose a risk to health in its own right,
      although little is known about their effects on mental health. We examined the
      association between several types of common sedentary behaviors (TV viewing,
      Internet use, reading) and different aspects of mental health. METHODS: We
      conducted a 2-yr follow-up of 6359 (age 64.9 +/- 9.1 yr) men and women from the
      English Longitudinal Study of Ageing, a cohort of community-dwelling older
      adults. Self-reported TV viewing time, reading, and use of the Internet was
      assessed at baseline. Mental health was assessed using the eight-item Centre of
      Epidemiological Studies Depression scale to measure depressive symptoms and
      neuropsychological tests of memory and verbal fluency to assess cognitive
      function. RESULTS: At baseline, TV viewing time (>= 6 vs. <2 h . d(-1)) was
      associated with higher depressive symptoms (coefficient = 0.49, 95% confidence
      interval [CI] = 0.63 to 0.35) and poorer global cognitive function (coefficient =
      -1.16, 95% CI = -1.00 to -1.31). Conversely, participants using the Internet
      reported lower depressive symptoms (coefficient = -0.58, 95% CI = -0.50 to -0.66)
      and higher global cognitive function (coefficient = 1.27, 95% CI = 1.37 to 1.18).
      There was no association between any sedentary behaviors at baseline and change
      in mental health measures over follow-up, suggesting that the difference in
      scores persisted but did not increase over time. CONCLUSIONS: Some, but not all
      sedentary behaviors, are linked to adverse mental health. It is likely that these
      associations are being driven by the contrasting environmental and social
      contexts in which they occur.

PMID- 24121249
TI  - Intermittent stretch reduces force and central drive more than continuous
      stretch.
AB  - INTRODUCTION: The relative contributions of central versus peripheral factors to
      the force loss induced by acute continuous and intermittent plantarflexor
      stretches were studied. METHODS: Eighteen healthy young men with no apparent
      tissue stiffness limitations randomly performed 1) one 5-min stretch (continuous
      stretch [CS]), 2) five 1-min stretches (intermittent stretch [IS]), and 3) a
      control condition, on three separate days. The stretches were constant-torque
      ankle stretches performed on an isokinetic dynamometer. Gastrocnemius medialis
      oxygenation status was quantified during stretch using near-infrared
      spectroscopy. Measures of isometric plantarflexor peak torque (Tpeak), voluntary
      activation (%VA; interpolated twitch technique), EMG amplitude normalized by Mmax
      (EMG:M), V-wave amplitude, and excitation-contraction (E-C) coupling efficiency
      (torque ratio between 20- and 80-Hz tetanic stimulations [20:80]) were taken
      before, immediately, and 15 and 30 min after each condition. RESULTS: IS caused
      substantial cyclic variations in tissue oxygenation, but CS resulted in a greater
      decrease in oxyhemoglobin concentration. Voluntary Tpeak decreased more after IS
      (-23.8%) than CS (-14.3%) and remained significantly depressed until 30 min after
      IS only (-5.6%). EMG:M (-27.7%) and %VA (-15.9%) were reduced only after IS.
      After CS and IS, the magnitude of decrease in Tpeak was correlated with decreases
      in EMG:M (r = 0.81 and 0.89, respectively), %VA (r = 0.78 and 0.93), and V-wave
      (r = 0.51, only after IS). Tetanic torque values (20 and 80 Hz) were decreased
      after IS (-13.1% and -6.4%, respectively) and CS (-10.9% and -6.7%,
      respectively), but 20:80 was not different from the control group. CONCLUSION:
      These results suggest that IS reduced Tpeak more than CS, and these reductions
      were strongly associated with a depression in central drive.

PMID- 24121250
TI  - Methodological issues in life cycle assessment of mixed-culture
      polyhydroxyalkanoate production utilising waste as feedstock.
AB  - Assessing the environmental performance of emerging technologies using life cycle
      assessment (LCA) can be challenging due to a lack of data in relation to
      technologies, application areas or other life cycle considerations, or a lack of
      LCA methodology that address the specific concerns. Nevertheless, LCA can be a
      valuable tool in the environmental optimisation in the technology development
      phase. One emerging technology is the mixed-culture production of
      polyhydroxyalkanoates (PHAs). PHA production by pure microbial cultures has been
      developed and assessed in several LCAs during the previous decade. Recent
      developments within mixed-culture PHA production call for environmental
      assessment to guide in technology development. Mixed-culture PHA production can
      use the organic content in wastewater as a feedstock; the production may then be
      integrated with wastewater treatment (WWT) processes. This means that mixed
      culture PHA is produced as a by-product from services in the WWT. This article
      explores different methodological challenges for LCA of mixed-culture PHA
      production using organic material in wastewater as feedstock. LCAs of both pure-
      and mixed-culture PHA production were reviewed. Challenges, similarities and
      differences when assessing PHA production by mixed- or pure-cultures were
      identified and the resulting implications for methodological choices in LCA were
      evaluated and illustrated, using a case study with mixed- and pure-culture PHA
      model production systems, based on literature data. Environmental impacts of
      processes producing multiple products or services need to be allocated between
      the different products or services. Such situations occur both in feedstock
      production and when the studied system is providing multiple functions. The
      selection of allocation method is shown to determine the LCA results. The type of
      data used, for electricity in the energy system, is shown to be important for the
      results, which indicates, a strong regional dependency of results for systems
      with electricity use as an environmental hot spot. The importance of assessing
      water use, an environmental impact not assessed by any of the reviewed studies,
      is highlighted. 

PMID- 24121251
TI  - Metabolic labeling and membrane fractionation for comparative proteomic analysis
      of Arabidopsis thaliana suspension cell cultures.
AB  - Plasma membrane microdomains are features based on the physical properties of the
      lipid and sterol environment and have particular roles in signaling processes.
      Extracting sterol-enriched membrane microdomains from plant cells for proteomic
      analysis is a difficult task mainly due to multiple preparation steps and sources
      for contaminations from other cellular compartments. The plasma membrane
      constitutes only about 5-20% of all the membranes in a plant cell, and therefore
      isolation of highly purified plasma membrane fraction is challenging. A
      frequently used method involves aqueous two-phase partitioning in polyethylene
      glycol and dextran, which yields plasma membrane vesicles with a purity of 95%
      (1). Sterol-rich membrane microdomains within the plasma membrane are insoluble
      upon treatment with cold nonionic detergents at alkaline pH. This detergent
      resistant membrane fraction can be separated from the bulk plasma membrane by
      ultracentrifugation in a sucrose gradient (2). Subsequently, proteins can be
      extracted from the low density band of the sucrose gradient by
      methanol/chloroform precipitation. Extracted protein will then be trypsin
      digested, desalted and finally analyzed by LC-MS/MS. Our extraction protocol for
      sterol-rich microdomains is optimized for the preparation of clean detergent
      resistant membrane fractions from Arabidopsis thaliana cell cultures. We use full
      metabolic labeling of Arabidopsis thaliana suspension cell cultures with K(15)NO3
      as the only nitrogen source for quantitative comparative proteomic studies
      following biological treatment of interest (3). By mixing equal ratios of labeled
      and unlabeled cell cultures for joint protein extraction the influence of
      preparation steps on final quantitative result is kept at a minimum. Also loss of
      material during extraction will affect both control and treatment samples in the
      same way, and therefore the ratio of light and heave peptide will remain
      constant. In the proposed method either labeled or unlabeled cell culture
      undergoes a biological treatment, while the other serves as control (4). 

PMID- 24121252
TI  - PPyDEP: a new approach to microparticle manipulation employing polymer-based
      electrodes.
AB  - In this work, a novel approach to 3-dimensional (3D) electrode fabrication, based
      on electrodeposited polypyrrole (PPy), for dielectrophoresis (DEP) is described.
      3D PPy electrodes with post and cage geometries were grown over planar
      interdigitated electrodes. Computational modelling and experimental work were
      carried out to assess the performance of the proposed electrode geometries. It
      was found that these new electrode geometries enhanced the dielectrophoretic
      trapping efficiency for polystyrene beads by exhibiting larger variations of the
      electric field and by affecting a larger volume of the fluid sample than planar
      electrodes. Applications of this work include, but are not limited to,
      environmental monitoring, food safety control, clinical analysis, and clean
      energy production. 

PMID- 24121253
TI  - Oxidized dextrins as alternative crosslinking agents for polysaccharides:
      application to hydrogels of agarose-chitosan.
AB  - Hydrogel networks that combine suitable physical and biomechanical
      characteristics for tissue engineering scaffolds are in demand. The aim of this
      work was the development of hydrogel networks based on agarose and chitosan using
      oxidized dextrins as low cytotoxicity crosslinking agents, paying special
      attention to the study of the influence of the polysaccharide composition and
      oxidation degree of the dextrins in the final characteristics of the network. The
      results show that the formation of an interpenetrating or a semi-interpenetrating
      polymer network was mainly dependent on a minimum agarose content and degree of
      oxidation of dextrin. Spectroscopic, thermal and swelling analysis revealed good
      compatibility with an absence of phase separation of polysaccharides at
      agarose:chitosan proportions of 50:50 and 25:75. The analysis of atomic force
      microscopy images showed the formation of a fibrillar microstructure whose
      distribution within the crosslinked chitosan depended mainly on the crosslinker.
      All materials exhibited the viscoelastic behaviour typical of gels, with a
      constant storage modulus independent of frequency for all compositions. The
      stiffness was strongly influenced by the degree of oxidation of the crosslinker.
      Cellular response to the hydrogels was studied with cells of different strains,
      and cell adhesion and proliferation was correlated with the homogeneity of the
      samples and their elastic properties. Some hydrogel formulations seemed to be
      candidates for tissue engineering applications such as wound healing or soft
      tissue regeneration. 

PMID- 24121254
TI  - A general route towards well-defined magneto- or fluorescent-plasmonic
      nanohybrids.
AB  - Herein, we present a general route towards defined nanohybrids, comprised of a
      fluorescent quantum dot (QD) or superparamagnetic iron oxide (Fe2O3) nanocrystal
      core and a tuneable corona of plasmonic gold or silver nanoparticles (NPs),
      adhered by a cross-linked poly(isoprene)-b-poly(ethylene glycol) diblock
      copolymer (PI-b-PEG) matrix. To this end, the PEG-terminus of the amphiphilic
      polymer was acylated with lipoic acid (LA), which, as is known, forms quasi
      covalent Au-thiol- or Ag-thiol-bonds. Surprisingly, by variation of the ratio of
      the different NPs, inverse core/satellite structures bearing QDs or Fe2O3 around
      a metallic NP core were obtained. Furthermore, gold NPs or even closed gold
      shells were grown by in situ reductive deposition of Au(3+) ions on Fe2O3 NP
      seeds. Finally, in order to demonstrate the scope of the method, ternary
      nanohybrids, composed of QDs, Fe2O3 and Au NPs, were accomplished. All magneto
      plasmonic and fluorescent-plasmonic materials were thoroughly characterized by
      absorption and emission spectroscopy, TEM and TEM-EDX. Antibody conjugation to
      these novel nanohybrids proved their practical utility in a prototype
      immunoassay. 

PMID- 24121256
TI  - Targeting quality in surgery.

PMID- 24121255
TI  - Association of age at onset in Huntington disease with functional promoter
      variations in NPY and NPY2R.
AB  - Huntington disease (HD) is caused by the expansion of a CAG repeat within exon 1
      of the HTT gene. Although the variation in age at onset (AO) is partly explained
      by the lengths of the expanded repeats, the unexplained variation is highly
      heritable, emphasizing the role of the so-called genetic background on disease
      expression. Neuropeptide Y (NPY) has been implicated in the modulation of
      neuroprotection, neurogenesis, and neuroinflammation. Therefore, the aim of the
      present study was to analyze different single nucleotide polymorphisms (SNPs) in
      order to test the possibility that genetic variation in NPY or three of its
      receptor genes (NPY1R, NPY2R, and NPY5R) may explain some of the variation in AO
      of HD motor manifestations, in a comprehensive cohort of 487 German HD patients.
      We found modest association of the AO with two NPY promoter variations and a
      highly significant association with a NPY2R promoter SNP (rs2234759; p = 0.0004).
      Investigating the functional impact of rs2234759 by luciferase assays revealed
      that the high-expression NPY2R genotypes were associated with later AO in HD.
      Additionally, treatment of PC12 cells expressing mutant huntingtin (htt) exon 1
      with NPY and the NPY2R agonist NPY(3-36) has a protective effect against mutant
      htt-induced cell death. Thus, NPY might act through Y2 receptors to slow down the
      course of HD, and hence, this peptide could be of interest as a possible
      therapeutic agent.

PMID- 24121257
TI  - Aspiration and allograft injury secondary to gastroesophageal reflux occur in the
      immediate post-lung transplantation period (prospective clinical trial).
AB  - OBJECTIVES: To provide novel pilot data to quantify reflux, aspiration, and
      allograft injury immediately post-lung transplantation. BACKGROUND: Asymptomatic
      reflux/aspiration, associated with allograft dysfunction, occurs in lung
      transplant recipients. Early fundoplication has been advocated. Indications for
      surgery include elevated biomarkers of aspiration (bile salts) in bronchoalveolar
      lavage fluid (BALF). Measurements have been mostly documented after the immediate
      posttransplant period. We report the first prospective study of reflux/aspiration
      immediately posttransplantation to date. METHODS: Lung transplant recipients were
      recruited over 12 months. At 1 month posttransplantation, patients completed a
      Reflux Symptom Index questionnaire and underwent objective assessment for reflux
      (manometry and pH/impedance). Testing was performed on maintenance proton pump
      inhibitor. BALF was assessed for pepsin, bile salts, interleukin-8 and
      neutrophils. RESULTS: Eighteen lung transplant recipients, median age of 46 years
      (range: 22-59 years), were recruited. Eight of 18 patients had abnormal
      esophageal peristalsis. Five of 17 patients were positive on Reflux Symptom Index
      questionnaire. Twelve of 17 patients had reflux. Three patients exclusively had
      weakly acid reflux. Median acid exposure was 4.8% (range: 1%-79.9%) and median
      esophageal volume exposure was 1.6% (range: 0.7-5.5). There was a median of 72
      reflux events (range: 27-147) per 24 hours. A correlation existed between Reflux
      Symptom Index score and proximal reflux (r = 0.533, P = 0.006). Pepsin was
      detected in 11 of 15 BALF samples signifying aspiration (median: 18 ng/mL; range:
      0-43). Bile salts were undetectable, using spectrophotometry and rarely
      detectable using dual mass spectrometry (2/15) (levels 0.2 and 1.2 MUmol/L).
      Lavage interleukin-8 and neutrophil levels were elevated. A correlation existed
      between proximal reflux events and neutrophilia (r = 0.52, P = 0.03).
      CONCLUSIONS: Lung transplant recipients should be routinely assessed for
      reflux/aspiration within the first month posttransplant. Reflux/aspiration can be
      present early postoperatively. Pepsin was detected suggesting aspiration. Bile
      salts were rarely detected. Proximal reflux events correlated with neutrophilia,
      linked to allograft dysfunction and mortality. These results support the need for
      early assessment of reflux/aspiration, which may inform fundoplication.

PMID- 24121258
TI  - Surgical management of congenital intrahepatic bile duct dilatation, Caroli's
      disease and syndrome: long-term results of the French Association of Surgery
      Multicenter Study.
AB  - OBJECTIVE: To assess clinical presentation and long-term results of surgical
      management of congenital intrahepatic bile duct dilatation (IHBDD) (Caroli
      disease and syndrome) in a multicenter setting. BACKGROUND: Congenital IHBDD
      predisposes to biliary stasis, resulting in intrahepatic lithiasis, septic
      complications, and cholangiocarcinoma. Although liver resection (LR) is
      considered to be the treatment of choice for unilobar disease extent into the
      liver, the management of bilobar disease and/or associated congenital hepatic
      fibrosis remains challenging. METHODS: From 1978 to 2011, a total of 155 patients
      (median age: 55.7 years) were enrolled from 26 centers. Bilobar disease, Caroli
      syndrome, liver atrophy, and intrahepatic stones were encountered in 31.0%,
      19.4%, 27.7%, and 48.4% of patients, respectively. A complete resection of
      congenital intrahepatic bile ducts was achieved in 90.5% of the 148 patients who
      underwent surgery. RESULTS: Postoperative mortality was nil after anatomical LR
      (n = 111) and 10.7% after liver transplantation (LT) (n = 28). Grade 3 or higher
      postoperative morbidity occurred in 15.3% of patients after LR and 39.3% after
      LT. After a median follow-up of 35 months, the 5-year overall survival rate was
      88.5% (88.7% after LT), and the Mayo Clinic score was considered as excellent or
      good in 86.0% of patients. The 1-year survival rate was 33.3% for the 8 patients
      (5.2%) who presented with coexistent cholangiocarcinoma. CONCLUSIONS: LR for
      unilobar and LT for diffuse bilobar congenital IHBDD complicated with cholangitis
      and/or portal hypertension achieved excellent long-term patient outcomes and
      survival. Because of the bad prognosis of cholangiocarcinoma and the sizeable
      morbidity-mortality after LT, timely indication for surgical treatment is of
      major importance.

PMID- 24121259
TI  - The influence of CTGF single-nucleotide polymorphisms on outcomes in Crohn's
      disease.
AB  - OBJECTIVE: To examine the association between single-nucleotide polymorphisms
      (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after
      terminal ileal resection for Crohn's disease. BACKGROUND: The primary indication
      for intestinal resection in Crohn's disease is fibrostenotic terminal ileal
      disease. CTGF is a cytokine overexpressed in the intestine of patients with
      Crohn's disease that influences outcomes in other disease processes. METHODS: DNA
      was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients
      with Crohn's disease who had undergone terminal ileal resection between 1981 and
      2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698,
      and rs9399005), which modulate nuclear factor binding and CTGF production, and a
      smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped
      using the Montreal Disease Classification. RESULTS: Sixty-seven of 147 patients
      (45.6%) were male; the mean age at diagnosis was 30.3 +/- 12.6 years and the mean
      follow-up duration was 8.3 +/- 7.1 years. Genotype-phenotype analysis
      demonstrated that the rs6918698GG genotype was associated with an older age of
      disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence
      interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated
      with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and
      negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144
      0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of
      Crohn's disease after intestinal resection. On multivariate analysis, male sex
      odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked
      tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas
      having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617;
      P = 0.005) of surgical recurrence. CONCLUSIONS: These data implicate the
      rs6918698GG genotype with an age of disease onset of greater than 40 years in
      Crohn's disease whereas the rs9402373CC genotype is associated with a
      nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the
      rate of recurrence after terminal ileal resection for Crohn's disease.

PMID- 24121260
TI  - beta-Sitosterol modulates TLR4 receptor expression and intracellular MyD88
      dependent pathway activation in J774A.1 murine macrophages.
AB  - Recent evidence has shown that dietary phytosterols (PS) possess anti
      inflammatory properties both in vivo and in vitro. Our previous work shows that
      PS beta-Sitosterol (SIT), may function by down-regulating pro-inflammatory
      transcription factors NF-kB and STAT1 in response to LPS stimulation, possibly
      through modulation of the TLR4 pathway. The objective in this study was to
      determine the effects of SIT on TLR4 surface expression and localization into
      lipid rafts, as well as to investigate its effects on intracellular MyD88
      dependent pathway activation. J774A.1 macrophages were pre-treated with
      cyclodextrin vehicle loaded with cholesterol or SIT, then stimulated with LPS
      (100 ng/ml) for 30 min. ImageStream cytometry demonstrated that SIT down
      regulates TLR4 expression without affecting lipid raft distribution. Western blot
      demonstrated that SIT down-regulated the adaptor protein MyD88 and the activity
      of IRAK1 but increased SOCS3 expression. Together, these results provide evidence
      that SIT may indeed elicit anti-inflammatory properties by down-regulating some
      components of the TLR4 pathway.

PMID- 24121261
TI  - Frax prediction without BMD for assessment of osteoporotic fracture risk.
AB  - OBJECTIVE: To compare Fracture Risk Assessment Tool (FRAX) calculations with and
      without bone mineral density (BMD) in predicting the 10-year probability of hip
      and major osteoporotic fractures (MOF). METHODS: A cross-sectional review of
      patients requiring screening for osteoporosis as part of their routine medical
      care was conducted. Postmenopausal women and men over 50 years of age who were
      never diagnosed with osteoporosis or treated with U.S. Food and Drug
      Administration-approved agents for osteoporosis were included. Height, weight,
      FRAX questionnaire, femoral neck BMD, and T-score data were obtained. FRAX scores
      with BMD (FRAX/BMD) and without BMD (FRAX) were calculated. Subjects were
      separated on the basis of identical and different treatment recommendations.
      Fracture risk factors were compared between groups using simple Student's t test
      analysis of numerical variables and Fisher's exact test analysis of binary
      variables. RESULTS: Of 151 total subjects, 127 (84%) had identical fracture risk
      predictions with or without BMD included in the FRAX calculation. Thirty subjects
      met treatment criteria and 97 did not, but the FRAX prediction was the same with
      risk factors alone or with risk factors plus BMD. Age was the only risk factor
      that was significantly different between those with identical and different
      predictions (median age, 64.42 and 76.25 years, respectively; P<.001).
      CONCLUSION: In most cases, FRAX alone provides the same prediction as FRAX with
      BMD. Younger age is more indicative of an identical prediction.

PMID- 24121265
TI  - Persistent organic pollutant concentrations in fledglings of two arctic seabird
      species.
AB  - Persistent organic pollutants (POPs) and stable isotopes were measured in muscle
      from fledglings of two arctic seabird species, Northern fulmar (Fulmarus
      glacialis) and Black-legged kittiwakes (Rissa tridactyla). The purpose was to
      compare POP concentrations between species, in an age class that is highly
      vulnerable to POPs but little studied, relate to diet using stable isotopes, and
      quantify differences across life stages (egg to adult). Northern fulmar
      fledglings had significantly higher POP concentrations than kittiwake, consistent
      with results reported for adults of these species. Surprisingly, carbon and
      nitrogen stable isotopes did not differ between species, which does not match
      data for, or the known feeding ecology, of the adults. Fulmar/kittiwake POP
      concentration ratios varied across life stages indicating variable POP exposure
      and accumulation with age in seabirds, indicating that of the use of avian
      species-specific thresholds should only be done with caution in ecosystem-based
      POP risk management. 

PMID- 24121263
TI  - Clinical practice guidelines for healthy eating for the prevention and treatment
      of metabolic and endocrine diseases in adults: cosponsored by the American
      Association of Clinical Endocrinologists/the American College of Endocrinology
      and the Obesity Society: executive summary.

PMID- 24121266
TI  - If you could turn back time: understanding transgenerational latent effects of
      developmental exposure to contaminants.
AB  - Latent effects result from embryonic experiences but manifest in later stages of
      ontogeny. Our objective was to better understand how developmental exposure to
      contaminants influence life history traits and tolerance to novel stress in the
      freshwater gastropod, Physa pomilia. Ten egg masses were exposed to each of three
      initial treatments including control, 2.5 MUg/L cadmium (Cd), and 10 MUg/L Cd;
      there was no effect of this initial treatment on hatching success. At hatching,
      snails were transferred to cadmium-free water. Three weeks later, snails were
      divided among four secondary treatments including control, 50 MUg/L Cd, 150 MUg/L
      Cd, and 35  degrees C. Developmental Cd exposure plus secondary temperature
      stress caused the most adverse effects. Surprisingly, developmental Cd exposure
      alone was enough to cause significant decreases in reproductive success a
      generation later. That effects can manifest as transgenerational decrements in
      reproductive success suggests that latent effects are important and have longer
      lasting consequences than previously considered. 

PMID- 24121267
TI  - Role of sectoral and multi-pollutant emission control strategies in improving
      atmospheric visibility in the Yangtze River Delta, China.
AB  - The Community Multi-scale Air Quality modeling system is used to investigate the
      response of atmospheric visibility to the emission reduction from different
      sectors (i.e. industries, traffic and power plants) in the Yangtze River Delta,
      China. Visibility improvement from exclusive reduction of NOx or VOC emission was
      most inefficient. Sulfate and organic aerosol would rebound if NOx emission was
      exclusively reduced from any emission sector. The most efficient way to improve
      the atmospheric visibility was proven to be the multi-pollutant control
      strategies. Simultaneous emission reductions (20-50%) on NOx, VOC and PM from the
      industrial and mobile sectors could result in 0.3-1.0 km visibility improvement.
      And the emission controls on both NOx (85%) and SO2 (90%) from power plants
      gained the largest visibility improvement of up to 4.0 km among all the
      scenarios. The seasonal visibility improvement subject to emission controls was
      higher in summer while lower in the other seasons. 

PMID- 24121268
TI  - The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent
      on the proteasomal ubiquitin receptor S5a.
AB  - p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the
      proteasome for degradation. Despite the importance of this in regulating the p53
      pathway, little is known about the mechanisms of proteasomal recognition of
      ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the
      proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation
      and results in the accumulation of ubiquitinated p53. Overexpression of a
      dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs
      (UIM)s, but which can be incorporated into the proteasome, also causes the
      stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue
      experiments confirm that the UIMs of S5a are required for the maintenance of low
      p53 levels. These observations indicate that S5a participates in the recognition
      of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect
      on the rate of degradation of Mdm2, indicating that proteasomal recognition of
      Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an
      increase in the transcriptional activity of p53. The selective stabilization of
      p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes
      a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a
      dominant role in the response to targeting S5a. This study provides evidence for
      alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in
      recognition by the proteasome could provide a means to modulate the relative
      stability of p53 and Mdm2 in response to cellular signals. In addition, they
      could be exploited for p53-activating therapies. This work shows that the
      degradation of proteins by the proteasome can be selectively dependent on S5a in
      human cells, and that this selectivity can extend to an E3 ubiquitin ligase and
      its substrate. 

PMID- 24121269
TI  - Aggressive acute myeloid leukemia in PU.1/p53 double-mutant mice.
AB  - PU.1 downregulation within hematopoietic stem and progenitor cells (HSPCs) is the
      primary mechanism for the development of acute myeloid leukemia (AML) in mice
      with homozygous deletion of the upstream regulatory element (URE) of PU.1 gene.
      p53 is a well-known tumor suppressor that is often mutated in human hematologic
      malignancies including AML and adds to their aggressiveness; however, its genetic
      deletion does not cause AML in mouse. Deletion of p53 in the PU.1(ure/ure) mice
      (PU.1(ure/ure)p53(-/-)) results in more aggressive AML with shortened overall
      survival. PU.1(ure/ure)p53(-/-) progenitors express significantly lower PU.1
      levels. In addition to URE deletion we searched for other mechanisms that in the
      absence of p53 contribute to decreased PU.1 levels in PU.1(ure/ure)p53(-/-) mice.
      We found involvement of Myb and miR-155 in downregulation of PU.1 in aggressive
      murine AML. Upon inhibition of either Myb or miR-155 in vitro the AML progenitors
      restore PU.1 levels and lose leukemic cell growth similarly to PU.1 rescue. The
      MYB/miR-155/PU.1 axis is a target of p53 and is activated early after p53 loss as
      indicated by transient p53 knockdown. Furthermore, deregulation of both MYB and
      miR-155 coupled with PU.1 downregulation was observed in human AML, suggesting
      that MYB/miR-155/PU.1 mechanism may be involved in the pathogenesis of AML and
      its aggressiveness characterized by p53 mutation.

PMID- 24121272
TI  - SRChing for the substrates of Src.
AB  - By the mid 1980's, it was clear that the transforming activity of oncogenic Src
      was linked to the activity of its tyrosine kinase domain and attention turned to
      identifying substrates, the putative next level of control in the pathway to
      transformation. Among the first to recognize the potential of phosphotyrosine
      specific antibodies, Parsons and colleagues launched a risky shotgun-based
      approach that led ultimately to the cDNA cloning and functional characterization
      of many of today's best-known Src substrates (for example, p85-Cortactin, p110
      AFAP1, p130Cas, p125FAK and p120-catenin). Two decades and over 6000 citations
      later, the original goals of the project may be seen as secondary to the enormous
      impact of these protein substrates in many areas of biology. At the request of
      the editors, this review is not restricted to the current status of the
      substrates, but reflects also on the anatomy of the project itself and some of
      the challenges and decisions encountered along the way. 

PMID- 24121270
TI  - p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified
      epithelia.
AB  - The retinoblastoma gene product (pRb) controls proliferation and differentiation
      processes in stratified epithelia. Importantly, and in contrast to other tissues,
      Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin
      dependent kinase inhibitor p21 regulates proliferation and differentiation in the
      absence of pRb, we analyzed the consequences of deleting p21 in pRb-ablated
      stratified epithelia (hereafter pRb(DeltaEpi);p21-/-). These mice display an
      enhancement of the phenotypic abnormalities observed in pRb(DeltaEpi) animals,
      indicating that p21 partially compensates pRb absence. Remarkably,
      pRb(DeltaEpi);p21-/- mice show an acute skin inflammatory phenotype and develop
      spontaneous epithelial tumors, particularly affecting tongue and oral tissues.
      Biochemical analyses and transcriptome studies reveal changes affecting multiple
      pathways, including DNA damage and p53-dependent signaling responses. Comparative
      metagenomic analyses, together with the histopathological profiles, indicate that
      these mice constitute a faithful model for human head and neck squamous cell
      carcinomas. Collectively, our findings demonstrate that p21, in conjunction with
      pRb, has a central role in regulating multiple epithelial processes and
      orchestrating specific tumor suppressor functions. 

PMID- 24121271
TI  - The retinoblastoma tumor suppressor pathway modulates the invasiveness of ErbB2
      positive breast cancer.
AB  - The processes that control the progression of ductal carcinoma in situ (DCIS) to
      invasive breast cancer remain poorly understood. Epidermal growth factor receptor
      2 (ErbB2) overexpression is common in DCIS, as is disruption of the
      retinoblastoma tumor suppressor (RB) pathway. Here, we examined the cooperative
      impact of ErbB2 and RB deregulation on facets of disease progression. Our studies
      demonstrate that RB deficiency altered the expression of key molecules needed for
      proper cellular organization and epithelial cell-cell adhesion as part of a
      program related to the epithelial-to-mesenchymal transition (EMT). An increase in
      the invasive potential of ErbB2-overexpressing cells was observed upon RB
      depletion. Further, stable knockdown of RB resulted in invasive lesions in
      orthotopic xenograft assays, compared with DCIS-like lesions developing from RB
      proficient cells. Conversely, the invasive phenotype observed in ErbB2-positive
      cancer models was inhibited through CDK4/6 inhibition in an RB-dependent manner.
      Finally, in a cohort of DCIS cases, we show that, although elevated levels of
      ErbB2 are associated with increased risk of a subsequent DCIS recurrence, it is
      not associated with progression to invasive disease. In contrast, RB loss in
      ErbB2-positive DCIS cases was associated with increased risk for invasive breast
      cancer. Taken together, these data demonstrate a key role for the RB pathway in
      invasion associated with breast tumor progression, and shed light on the key
      molecular events that promote the progression of DCIS to invasive disease.

PMID- 24121273
TI  - Oncogenic suppression of PHLPP1 in human melanoma.
AB  - Akt is constitutively activated in up to 70% of human melanomas and has an
      important role in the pathogenesis of the disease. However, little is known about
      protein phosphatases that dephosphorylate and thereby inactivate it in melanoma
      cells. Here we report that suppression of pleckstrin homology domain and leucine
      rich repeat Ser/Thr protein phosphatase 1 (PHLPP1) by DNA methylation promotes
      Akt activation and has an oncogenic role in melanoma. While it is commonly
      downregulated, overexpression of PHLPP1 reduces Akt activation and inhibits
      melanoma cell proliferation in vitro, and retards melanoma growth in a xenograft
      model. In contrast, knockdown of PHLPP1 increases Akt activation, enhances
      melanoma cell and melanocyte proliferation, and results in anchorage-independent
      growth of melanocytes. Suppression of PHLPP1 involves blockade of binding of the
      transcription factor Sp1 to the PHLPP1 promoter. Collectively, these results
      suggest that suppression of PHLPP1 by DNA methylation contributes to melanoma
      development and progression.

PMID- 24121275
TI  - The MYB proto-oncogene suppresses monocytic differentiation of acute myeloid
      leukemia cells via transcriptional activation of its target gene GFI1.
AB  - The MYB gene is a master regulator of hematopoiesis and contributes to
      leukemogenesis in several species including humans. Although it is clear that MYB
      can promote proliferation, suppress apoptosis and block differentiation, the
      identities of the MYB target genes that mediate these effects have only been
      partially elucidated. Several studies, including our own, have collectively
      identified substantial numbers of MYB target genes, including candidates for each
      of these activities; however, functional validation, particularly in the case of
      differentiation suppression, has lagged well behind. Here we show that GFI1,
      which encodes an important regulator of hematopoietic stem cell (HSC) function
      and granulocytic differentiation, is a direct target of MYB in myeloid leukemia
      cells. Chromatin immunoprecipitation and reporter studies identified a functional
      MYB-binding site in the promoter region of GFI, whereas ectopic expression and
      small hairpin RNA-mediated knockdown of MYB resulted in concomitant increases and
      decreases, respectively, in GFI1 expression. We also demonstrate that GFI1, like
      MYB, can block the induced monocytic differentiation of a human acute myeloid
      leukemia cell line, and most importantly, that GFI1 is essential for MYB's
      ability to block monocytic differentiation. Thus, we have identified a target of
      MYB that is a likely mediator of its myeloid differentiation-blocking activity,
      and which may also be involved in MYB's activities in regulating normal HSC
      function and myeloid differentiation. 

PMID- 24121276
TI  - Chemical solution growth of ferroelectric oxide thin films and nanostructures.
AB  - Chemical solution deposition (CSD) provides a low-cost, versatile approach for
      processing of thin and ultrathin ferroelectric films, as well as short and high
      aspect ratio ferroelectric nanostructures. This review discusses the state of the
      art in the processing of ferroelectric oxide thin films and nanostructures by
      CSD, with special emphasis on nucleation and growth phenomena. The effects of
      choice of precursor solution, substrate and bottom electrode stack, and thermal
      treatment conditions on the nucleation and growth are examined. Furthermore,
      methods to control ferroelectric thin film's microstructure, including phase
      content, texture, grain size and chemical homogeneity, are reviewed. Lastly,
      current CSD-based methods for processing of ferroelectric oxide nanostructures
      are presented with special consideration of the structural development, as well
      as advantages and shortcomings associated with each method. Lead zirconate
      titanate, Pb(ZrxTi1-x)O3 (PZT), and barium titanate, BaTiO3 (BT), are used
      throughout the discussion, as specific examples for CSD processing of perovskite
      ferroelectrics. 

PMID- 24121274
TI  - HAI-2 suppresses the invasive growth and metastasis of prostate cancer through
      regulation of matriptase.
AB  - Dysregulation of cell surface proteolysis has been strongly implicated in
      tumorigenicity and metastasis. In this study, we delineated the role of
      hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa)
      cell migration, invasion, tumorigenicity and metastasis using a human PCa
      progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells
      were established through serial intraprostatic propagation of 103E human PCa
      cells and isolation of the metastatic cells from nearby lymph nodes. The invasion
      capability of these cells was revealed to gradually increase throughout the
      serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2
      but not HAI-1 was significantly decreased throughout the progression and occurred
      in parallel with increased activation of matriptase. The expression level and
      activity of matriptase increased whereas the HAI-2 protein level decreased over
      the course of orthotopic tumor growth in mice, which was consistent with the
      immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens.
      Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown.
      HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase
      activity and significantly decreased tumorigenicity and metastatic capability in
      orthotopically xenografted mice. These results suggest that during the
      progression of human PCa, matriptase activity is primarily controlled by HAI-2
      expression. The imbalance between HAI-2 and matriptase expression led to
      matriptase activation, thereby increasing cell migration, invasion,
      tumorigenicity and metastasis. 

PMID- 24121278
TI  - Graphene based electrochemical biosensor for label-free measurement of the
      activity and inhibition of protein tyrosine kinase.
AB  - In this paper, we report a simple, ultrasensitive and label-free method to
      evaluate the activity of protein tyrosine (Tyr) kinase based on the
      electrochemical signal of Tyr residues at a graphene modified glassy carbon
      electrode. It was found that graphene could enhance the electrochemical response
      of Tyr through electrocatalytic oxidation reaction. After phosphorylation by
      kinase, the phosphorylated Tyr (pTyr) is electro-inactive and the electrochemical
      signal is reduced. Therefore, the electrochemical response of Tyr residues in
      peptides can be used as a signal reporter to assay kinase activity. In this
      study, using Src-catalyzed Tyr-phosphorylation as a model, the activity of kinase
      can be evaluated with a linear range from 0.26 to 33.79 nM and an extraordinarily
      low detection limit of 0.087 nM. Moreover, this electrochemical biosensor can
      also be utilized for monitoring the inhibition of kinase using 4-amino-5-(4
      chlorophenyl)-7-(tert-butyl) pyrazolo [3,4-d] pyrimidine, a small molecule
      inhibitor. On the basis of the inhibitor concentration dependent Tyr oxidation
      signal, the IC50 value was estimated to be 99 nM. 

PMID- 24121277
TI  - Therapeutic targeting of constitutive PARP activation compromises stem cell
      phenotype and survival of glioblastoma-initiating cells.
AB  - Glioblastoma-initiating cells (GICs) are self-renewing tumorigenic sub
      populations, contributing to therapeutic resistance via decreased sensitivity to
      ionizing radiation (IR). GIC survival following IR is attributed to an augmented
      response to genotoxic stress. We now report that GICs are primed to handle
      additional stress due to basal activation of single-strand break repair (SSBR),
      the main DNA damage response pathway activated by reactive oxygen species (ROS),
      compared with non-GICs. ROS levels were higher in GICs and likely contributed to
      the oxidative base damage and single-strand DNA breaks found elevated in GICs. To
      tolerate constitutive DNA damage, GICs exhibited a reliance on the key SSBR
      mediator, poly-ADP-ribose polymerase (PARP), with decreased viability seen upon
      small molecule inhibition to PARP. PARP inhibition (PARPi) sensitized GICs to
      radiation and inhibited growth, self-renewal, and DNA damage repair. In vivo
      treatment with PARPi and radiotherapy attenuated radiation-induced enrichment of
      GICs and inhibited the central cancer stem cell phenotype of tumor initiation.
      These results indicate that elevated PARP activation within GICs permits
      exploitation of this dependence, potently augmenting therapeutic efficacy of IR
      against GICs. In addition, our results support further development of clinical
      trials with PARPi and radiation in glioblastoma. 

PMID- 24121279
TI  - Rapid bond rearrangement in core-excited molecular water.
AB  - The angular anisotropy of fragments created in the dissociation of core-electron
      excited water molecules is studied to probe the correlation between fragmentation
      channels, kinematics and molecular geometry. We present fragment kinetic
      measurements for water molecules where the inner-shell oxygen electron is excited
      to the unoccupied 4a1 and 2b2 valence molecular orbitals. The kinematics of
      individual fragmentation channels are measured using fully three-dimensional
      momentum imaging of fragments. The results show that the geometry of the molecule
      and the kinetic energy of fragments are strongly coupled in the atomisation
      process. In addition we identify a fragmentation process arising from bond
      rearrangement evidenced by the H2(+)-O(+) ion pair which is accessible for
      resonant excitation of the 1s electron. In all of the two-body fragmentation
      processes the dissociation takes place along the potential-energy surface, while
      atomisation reveals both dissociation along the potential surface and Coulomb
      explosion. The angular distribution of fragments suggests that the bond
      rearrangement is very rapid; likely on a sub 10 fs time scale. 

PMID- 24121280
TI  - Ask, listen, respect.

PMID- 24121281
TI  - Back to school! Selecting a DNP program.

PMID- 24121282
TI  - Endoplasmic reticulum stress in vasopressin neurons of familial diabetes
      insipidus model mice: aggregate formation and mRNA poly(A) tail shortening.
AB  - The immunoglobulin heavy chain binding protein (BiP) is an endoplasmic reticulum
      (ER) chaperone, which binds to newly synthesized secretory and transmembrane
      proteins to facilitate protein folding. BiP mRNA is expressed in the arginine
      vasopressin (AVP) neurons in the supraoptic nucleus of wild-type mice even in
      basal conditions, and the expression levels increase in response to dehydration.
      These data suggest that AVP neurons are subjected to ER stress. Familial
      neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene
      locus of AVP. The mutant proteins could accumulate in the ER and possibly
      increase ER stress in the AVP neurons. We bred mice possessing a mutation causing
      FNDI, which manifested progressive polyuria, as do the patients with FNDI.
      Electron microscopic analyses demonstrated that aggregates accumulated in the ER
      of AVP neurons in FNDI mice. Despite polyuria, which could potentially induce
      dehydration, AVP mRNA expression was decreased in the supraoptic nucleus, and the
      AVP mRNA poly(A) tail length was shortened in FNDI mice compared with wild-type
      mice. Incubation of hypothalamic explants of wild-type mice with ER stressors
      caused shortening of the poly(A) tail length of AVP mRNA, accompanied by
      decreases in the expression. These data revealed a mechanism by which ER stress
      decreases poly(A) tail length of AVP mRNA, and this reduces the load of unfolded
      proteins that form the aggregates in ER of the AVP neurons in FNDI mice. 

PMID- 24121283
TI  - Cortical control of the autonomic nervous system.
AB  - NEW FINDINGS: What is the topic of this review? The pathways in the brain by
      which visceral information, in particular cardiopulmonary afferents, ascend to
      the cerebral cortex have been delineated in animal models. Studies using
      functional magnetic resonance imaging in humans have confirmed what was known
      from the animal studies and established the critical sites in the cerebral cortex
      of humans for autonomic control and the significance of these sites for cognitive
      emotional function. What advances does it highlight? Stimulation of
      cardiopulmonary afferents in humans has consistently resulted in activation in
      the insular cortex and the anterior cingulate cortex. It has been shown that
      individuals who are characterized as cardiovascular responders to mental stress
      have a different pattern of activity in the cortex related to the cardiac
      changes. A number of animal studies in the rat and cat have been particularly
      useful for determining the pathways and the sites in the forebrain and cortex
      that are responsible for autonomic control. For example, these experiments have
      demonstrated that there is a viscerotopically organized pathway, with the first
      site of termination in the nucleus of the solitary tract and with subsequent
      relays in the parabrachial nucleus and the ventroposterior parvocellular nucleus
      of the thalamus before final visceral afferent inputs in the insular cortex.
      Several neuroimaging studies in humans, using cardiopulmonary manipulations, have
      confirmed the importance of the insular cortex as a site of for visceral afferent
      inputs. The anterior cingulate cortex has also been implicated in cardiopulmonary
      control. Both the insular cortex and the infralimbic cortex have been shown to be
      involved in descending control of the cardiovascular system. Neuroimaging with
      functional magnetic resonance imaging has demonstrated that the cortical
      autonomic control pathways are different in individuals who are characterized as
      cardiovascular reactors to mental stress. There is evidence that this alteration
      in pathways in the cortex may be due to past experiences, including childhood
      trauma.

PMID- 24121284
TI  - The importance of the smooth muscle cytoskeleton to preterm labour.
AB  - Multiple mechanisms have been shown to regulate the onset of labour in a co
      operative and complex manner. One factor, myometrial stretch and associated
      increases in wall tension, has been implicated clinically in the initiation of
      labour and especially the aetiology of preterm labour. Recent work on the
      mechanisms involved has led to the finding that the intracellular Ca(2+)
      requirement for activation of the myometrial contractile filaments increases
      during gestation. The decreased Ca(2+) sensitivity correlates with an increase in
      the expression of caldesmon, an actin-binding protein and inhibitor of myosin
      activation, during pregnancy. In late pregnancy, an increase in extracellular
      signal-regulated kinase-mediated caldesmon phosphorylation occurs, which appears
      to reverse the inhibitory action of caldesmon during labour. Force generated by
      the myometrial contractile filaments is communicated across the plasmalemma to
      the uterine wall through focal adhesions. Phospho-tyrosine screening and mass
      spectrometry of stretched myometrial samples identified several stretch-activated
      focal adhesion proteins. This Src-mediated focal adhesion signalling appears to
      provide a tunable, i.e. regulated, tension sensor and force transmitter in the
      myometrial cell. In other parallel studies, biophysical measurements of smooth
      muscle compliance at both the cellular and tissue levels suggest that decreases
      in cellular compliance due to changing interactions of the actin cytoskeleton
      with the focal adhesions may also promote increases in uterine wall tension.
      These results, taken together, suggest that focal adhesion proteins and their
      interaction with the cytoskeleton may present a new mode of regulation of uterine
      contractility. 

PMID- 24121286
TI  - Confidence intervals for the parameters estimated from simulated O2 uptake
      kinetics: effects of different data treatments.
AB  - The behaviour of pulmonary O2 uptake following a moderate-intensity step exercise
      increment is usually described by a first brief increase, followed by a second
      exponential time course reaching the new steady state (phase II). The parameters
      describing the phase II kinetics are investigated by applying different data
      treatments to the acquired O2 uptake data to reduce the effects of their noise
      before running a non-linear regression procedure. The effects of different data
      treatments (nothing, resampling at various time intervals or averaging of more
      repetitions) on the precision and/or accuracy of the kinetics parameters
      estimated by non-linear regression with a simple mono-exponential model were
      investigated by artificially generating 10(5) simulated responses with average
      breath duration of 3.5 s. The simulations showed that, whatever the explored data
      treatment, the average estimated parameters were close to the theoretical ones.
      Nevertheless, in all the explored conditions, the non-linear regression provided
      narrower asymptotic confidence intervals than the real ones. In particular, when
      the responses were resampled at 1 s time intervals, the width of the asymptotic
      confidence interval for the time constant was 50% of the real one, even after the
      averaging of more repetitions. The reasons for this discrepancy were investigated
      further, allowing us to identify some methods to obtain the correct confidence
      interval of the O2 uptake kinetics parameters. The simplest method to obtain an
      asymptotic confidence interval close to the real one is to average more responses
      resampled to a time interval slightly longer than the average breath duration. 

PMID- 24121285
TI  - Kv7 and Kv11 channels in myometrial regulation.
AB  - Ion channels play a key role in defining myometrial contractility. Modulation of
      ion channel populations is proposed to underpin gestational changes in uterine
      contractility associated with the transition from uterine quiescence to active
      labour. Of the myriad ion channels present in the uterus, this article will focus
      upon potassium channels encoded by the KCNQ genes and ether-a-go-go-related (ERG)
      genes. Voltage-gated potassium channels encoded by KCNQ and ERG (termed Kv7 and
      Kv11, respectively) are accepted as major determinants of neuronal excitability
      and the duration of the cardiac action potential. However, there is now growing
      appreciation that these ion channels have a major functional impact in vascular
      and non-vascular smooth muscle. Moreover, Kv7 channels may be potential
      therapeutic targets for the treatment of preterm labour. 

PMID- 24121287
TI  - Patterns of habituation and clinical fluctuations in migraine.
AB  - BACKGROUND: Habituation deficit, suggesting a deregulation of cortical
      excitability, represents a typical hallmark of interictal stages of migraine. We
      previously demonstrated that several neurophysiological markers of altered
      cortical excitability are significantly correlated to spontaneous clinical
      fluctuations of migraine. We therefore aimed at verifying whether clinical
      fluctuations are correlated to specific patterns of somatosensory evoked
      potential (SEP) habituation. METHODS: We analyzed habituation after median nerve
      stimulation of both high-frequency oscillations (HFOs) and N20 SEP in 25 migraine
      patients and 18 healthy volunteers. Subjects underwent six consecutive series of
      500 stimuli. RESULTS: Migraine patients as a whole showed a significant
      habituation deficit of the N20 response. Moreover, spontaneously worsening
      patients show a clear potentiation of this wave in the last block of stimuli,
      whereas in spontaneously improving patients the N20 amplitude remained stable.
      Presynaptic HFOs were smaller in worsening patients and larger in improving ones,
      but they did not undergo habituation in patients as well as in healthy subjects.
      CONCLUSIONS: Potentiation of the N20 response in spontaneously worsening
      migraineurs confirms that the reduction of the thalamocortical drive plays a
      major role in migraine pathogenesis. Moreover, the stable pattern we observed in
      spontaneously improving patients suggests that compensatory mechanisms can also
      play an important role. The normal response to repeated stimuli of HFOs in
      migraineurs might indicate that, although its initial amount depends on clinical
      conditions, high-frequency thalamocortical drive remains stable during the
      stimulation and probably reflects the activity of a buffer mechanism.

PMID- 24121288
TI  - A calcium-dependent protein kinase interacts with and activates a calcium channel
      to regulate pollen tube growth.
AB  - Calcium, as a ubiquitous second messenger, plays essential roles in tip-growing
      cells, such as animal neurons, plant pollen tubes, and root hairs. However,
      little is known concerning the regulatory mechanisms that code and decode Ca(2+)
      signals in plants. The evidence presented here indicates that a calcium-dependent
      protein kinase, CPK32, controls polar growth of pollen tubes. Overexpression of
      CPK32 disrupted the polar growth along with excessive Ca(2+) accumulation in the
      tip. A search of downstream effector molecules for CPK32 led to identification of
      a cyclic nucleotide-gated channel, CNGC18, as an interacting partner for CPK32.
      Co-expression of CPK32 and CNGC18 resulted in activation of CNGC18 in Xenopus
      oocytes where expression of CNGC18 alone did not exhibit significant calcium
      channel activity. Overexpression of CNGC18 produced a growth arrest phenotype
      coupled with accumulation of calcium in the tip, similar to that induced by CPK32
      overexpression. Co-expression of CPK32 and CNGC18 had a synergistic effect
      leading to more severe depolarization of pollen tube growth. These results
      provide a potential feed-forward mechanism in which calcium-activated CPK32
      activates CNGC18, further promoting calcium entry during the elevation phase of
      Ca(2+) oscillations in the polar growth of pollen tubes.

PMID- 24121289
TI  - Phosphatidic acid regulates BZR1 activity and brassinosteroid signal of
      Arabidopsis.

PMID- 24121290
TI  - Redox regulation of glycogen biosynthesis in the cyanobacterium Synechocystis sp.
      PCC 6803: analysis of the AGP and glycogen synthases.
AB  - Glycogen constitutes the major carbon storage source in cyanobacteria, as starch
      in algae and higher plants. Glycogen and starch synthesis is linked to active
      photosynthesis and both of them are degraded to glucose in the dark to maintain
      cell metabolism. Control of glycogen biosynthesis in cyanobacteria could be
      mediated by the regulation of the enzymes involved in this process, ADP-glucose
      pyrophosphorylase (AGP) and glycogen synthase, which were identified as putative
      thioredoxin targets. We have analyzed whether both enzymes were subjected to
      redox modification using purified recombinant enzymes or cell extracts in the
      model cyanobacterium Synechocystis sp. PCC 6803. Our results indicate that both
      AGP and glycogen synthases are sensitive to copper oxidation. However, only AGP
      exhibits a decrease in its enzymatic activity, which is recovered after reduction
      by DTT or reduced thioredoxin (TrxA), suggesting a redox control of AGP. In order
      to elucidate the role in redox control of the cysteine residues present on the
      AGP sequence (C45, C185, C320, and C337), they were replaced with serine. All AGP
      mutant proteins remained active when expressed in Synechocystis, although they
      showed different electrophoretic mobility profiles after copper oxidation,
      reflecting a complex pattern of cysteines interaction. 

PMID- 24121291
TI  - Arabidopsis coordinates the diurnal regulation of carbon allocation and growth
      across a wide range of photoperiods.
AB  - In short photoperiods, plants accumulate starch more rapidly in the light and
      degrade it more slowly at night, ensuring that their starch reserves last until
      dawn. To investigate the accompanying changes in the timing of growth,
      Arabidopsis was grown in a range of photoperiods and analyzed for rosette
      biomass, photosynthesis, respiration, ribosome abundance, polysome loading,
      starch, and over 40 metabolites at dawn and dusk. The data set was used to model
      growth rates in the daytime and night, and to identify metabolites that correlate
      with growth. Modeled growth rates and polysome loading were high in the daytime
      and at night in long photoperiods, but decreased at night in short photoperiods.
      Ribosome abundance was similar in all photoperiods. It is discussed how the
      amount of starch accumulated in the light period, the length of the night, and
      maintenance costs interact to constrain growth at night in short photoperiods,
      and alter the strategy for optimizing ribosome use. Significant correlations were
      found in the daytime and the night between growth rates and the levels of the
      sugar-signal trehalose 6-phosphate and the amino acid biosynthesis intermediate
      shikimate, identifying these metabolites as hubs in a network that coordinates
      growth with diurnal changes in the carbon supply. 

PMID- 24121292
TI  - A high-density SNP genotyping array for rice biology and molecular breeding.
AB  - A high-density single nucleotide polymorphism (SNP) array is critically important
      for geneticists and molecular breeders. With the accumulation of huge amounts of
      genomic re-sequencing data and available technologies for accurate SNP detection,
      it is possible to design high-density and high-quality rice SNP arrays. Here we
      report the development of a high-density rice SNP array and its utility. SNP
      probes were designed by screening more than 10 000 000 SNP loci extracted from
      the re-sequencing data of 801 rice varieties and an array named RiceSNP50 was
      produced on the Illumina Infinium platform. The array contained 51 478 evenly
      distributed markers, 68% of which were within genic regions. Several hundred rice
      plants with parent/F1 relationships were used to generate a high-quality cluster
      file for accurate SNP calling. Application tests showed that this array had high
      genotyping accuracy, and could be used for different objectives. For example, a
      core collection of elite rice varieties was clustered with fine resolution.
      Genome-wide association studies (GWAS) analysis correctly identified a
      characterized QTL. Further, this array was successfully used for variety
      verification and trait introgression. As an accurate high-throughput genotyping
      tool, RiceSNP50 will play an important role in both functional genomics studies
      and molecular breeding. 

PMID- 24121293
TI  - Combining metabolomics and gene expression analysis reveals that propionyl- and
      butyryl-carnitines are involved in late stages of arbuscular mycorrhizal
      symbiosis.
AB  - The arbuscular mycorrhizal (AM) symbiosis is a widespread mutualistic association
      between soil fungi (Glomeromycota) and the roots of most plant species. AM fungi
      are obligate biotrophs whose development is partially under the control of their
      plant host. We explored the possibility to combine metabolomic and transcriptomic
      approaches to find putative mycorrhiza-associated metabolites regulating AM
      fungal development. Methanol extracts of Medicago truncatula roots colonized or
      not with the AM fungus Rhizophagus irregularis were analyzed and compared by
      ultra-high-performance liquid chromatography (UHPLC), high-resolution mass
      spectrometry (Q-TOF), and multivariate statistical discrimination. We detected 71
      mycorrhiza-associated analytes exclusively present or at least 10-fold more
      abundant in mycorrhizal roots. To identify among these analytes those that could
      regulate AM fungal development, we fractionated by preparative and semi
      preparative HPLC the mycorrhizal and non-mycorrhizal root extracts and
      established how the 71 analytes were distributed among the fractions. Then we
      tested the activity of the fractions on germinating spores of R. irregularis by
      quantifying the expression of 96 genes known for their diverse in planta
      expression patterns. These investigations reveal that propionyl- and butyryl
      carnitines accumulated in mycorrhizal roots. The results suggest that these two
      molecules regulate fungal gene expression in planta and represent interesting
      candidates for further biological characterization. 

PMID- 24121294
TI  - A prospective emergency department-based study of pattern and outcome of
      neurologic and neurosurgical diseases in Haiti.
AB  - OBJECTIVE: To perform the first prospective survey of neurologic and
      neurosurgical emergency department (ED) admissions in Haiti. METHODS: Data of all
      ED admissions at 3 Haitian hospitals for 90 consecutive days per site were
      collected prospectively. Patients who were given a diagnosis of a neurologic or
      neurosurgical disorder by the ED physician were entered in a deidentified
      database including demographics, presenting symptoms, brain imaging (when
      available), requests for neurosurgical consultation, and outcome. RESULTS: Of the
      7628 patients admitted to the ED during this study, 1243 patients had a
      neurologic disorder, yielding an ED-based neurologic disease prevalence of 16%.
      The 3 most common neurologic diseases were cerebrovascular disease (31%),
      neurotrauma (28%), and altered mental status (12%). Neurosurgical pathologies
      represented 19% of all neurologic admissions with a combined ED-based disease
      prevalence of 3%. Mortality rate was 9%. The most common neurosurgical disease
      was neurotrauma (87%), caused by motor vehicle accidents (59%), falls (20%), and
      assault (17%). Neurosurgical procedures were performed in 14 of 208 patients with
      a mortality rate of 33%. CONCLUSIONS: This prospective survey represents the
      first study of neurosurgical or neurologic disease patterns in Haiti. The results
      suggest specific disease priorities for this population that can guide efforts to
      improve Haitian health care and conduct more comprehensive epidemiologic studies
      in Haiti.

PMID- 24121295
TI  - Moniz to modern day magnetic resonance/computed tomographic angiography: the
      evolution of carotid nomenclature.

PMID- 24121296
TI  - Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic
      contact athletes.

PMID- 24121297
TI  - Resolution of cystic deterioration of the C1-2 articulation with posterior
      fusion: treatment implications for asymptomatic patients.

PMID- 24121298
TI  - Challenge of giant pituitary tumors.

PMID- 24121299
TI  - Metabonomic investigations of age- and batch-related variations in female NMRI
      mice using proton nuclear magnetic resonance spectroscopy.
AB  - The NMRI outbred mouse model is widely used for studying metabolic disease,
      toxicity, and infection, yet information regarding baseline metabolism of this
      murine strain is relatively sparse. Using different batches of female NMRI mice,
      we assessed the stability of the metabolic phenotype with increasing age and
      weight, and determined the influence of acclimatization on the metabolic profile
      of biofluids (urine, plasma, and faecal water). Differences in urinary
      concentrations of 3-ureidopropionate, 2-oxoisocaproate, trimethylamine, and
      glycine were detected between three batches of 9-week-old female NMRI mice using
      proton nuclear magnetic resonance ((1)H NMR) spectroscopy coupled with
      multivariate statistical analysis. An acclimatization period of 2 weeks was
      imposed after the mice entered the laboratory environment. Strong differences in
      the faecal metabolome pre- and post-acclimatization were found (reduction in
      amino acid concentrations), whilst the urine metabolome showed increased levels
      of trimethylamine-N-oxide, phenylacetyl glycine, and hippurate with decreased
      excretion of formate and betaine post-acclimatization. Temporal variation in the
      metabolite profiles over a 16-week study stabilized around 7-week-old animals.
      The results from this study strongly argue for inclusion of an acclimatization
      period prior to starting an investigative procedure, and suggest that the
      metabolic phenotypes of female NMRI mice are more stable at around 7 weeks of
      age. We have also identified a set of metabolites that are more susceptible to
      variation in concentration. This information can serve as a benchmark in order to
      establish confidence in systematic variation attributable to pathology or
      therapeutic intervention above the background metabolic variation in the NMRI
      mouse. 

PMID- 24121300
TI  - Generation of subcutaneous and intrahepatic human hepatocellular carcinoma
      xenografts in immunodeficient mice.
AB  - In vivo experimental models of hepatocellular carcinoma (HCC) that recapitulate
      the human disease provide a valuable platform for research into disease
      pathophysiology and for the preclinical evaluation of novel therapies. We present
      a variety of methods to generate subcutaneous or orthotopic human HCC xenografts
      in immunodeficient mice that could be utilized in a variety of research
      applications. With a focus on the use of primary tumor tissue from patients
      undergoing surgical resection as a starting point, we describe the preparation of
      cell suspensions or tumor fragments for xenografting. We describe specific
      techniques to xenograft these tissues i) subcutaneously; or ii) intrahepatically,
      either by direct implantation of tumor cells or fragments into the liver, or
      indirectly by injection of cells into the mouse spleen. We also describe the use
      of partial resection of the native mouse liver at the time of xenografting as a
      strategy to induce a state of active liver regeneration in the recipient mouse
      that may facilitate the intrahepatic engraftment of primary human tumor cells.
      The expected results of these techniques are illustrated. The protocols described
      have been validated using primary human HCC samples and xenografts, which
      typically perform less robustly than the well-established human HCC cell lines
      that are widely used and frequently cited in the literature. In comparison with
      cell lines, we discuss factors which may contribute to the relatively low chance
      of primary HCC engraftment in xenotransplantation models and comment on technical
      issues that may influence the kinetics of xenograft growth. We also suggest
      methods that should be applied to ensure that xenografts obtained accurately
      resemble parent HCC tissues. 

PMID- 24121301
TI  - Arbitrary tip orientation in STM simulations: 3D WKB theory and application to
      W(110).
AB  - We extend the orbital-dependent electron tunnelling model implemented within the
      three-dimensional (3D) Wentzel-Kramers-Brillouin (WKB) atom-superposition
      approach for simulating scanning tunnelling microscopy (STM) by including
      arbitrary tip orientations. The orientation of the tip is characterized by a
      local coordinate system centred on the tip apex atom obtained by a rotation with
      respect to the sample coordinate system. The rotation is described by the Euler
      angles. Applying our method, we highlight the role of the real-space shape of the
      electron orbitals involved in the tunnelling, and analyse the convergence and the
      orbital contributions of the tunnelling current above the W(110) surface
      depending on the orientation of a model tungsten tip. We also simulate STM images
      at constant-current condition, and find that their quality depends very much on
      the tip orientation. Some orientations result in protrusions on the images that
      do not occur above W atoms. The presence of such apparent atom positions makes it
      difficult to identify the exact position of surface atoms. It is suggested that
      this tip orientation effect should be considered in the evaluation of
      experimental STM images on other surfaces as well. The presented computationally
      efficient tunnelling model could prove to be useful for obtaining more
      information on the local tip geometry and orientation by comparing STM
      experiments to a large number of simulations with systematically varied tip
      orientations.

PMID- 24121302
TI  - Synthesis, X-ray structure, interactions with DNA, remarkable in vivo tumor
      growth suppression and nephroprotective activity of cis-tetrachloro-dipivalato
      dirhenium(III).
AB  - In this study we report the synthesis, the X-ray crystal structure and the in
      vivo tumor growth suppression and nephroprotective activity of bis
      dimethylsulfoxide-cis-tetrachlorodi-MU-pivalatodirhenium(III), cis
      Re2[(CH3)3CCOO]2Cl4.2(CH3)2SO (I). The interactions of I with DNA were also
      investigated by electrophoretic mobility shift assays, electronic absorption
      titrations, DeltaTm and viscosity measurements, which indicate that compound I
      interacts relatively strongly with the DNA (Kb 2.2*10(3)M(-1)), most likely by
      forming covalent interstrand cross-links, and by kinking and unwinding
      supercoiled DNA; moreover, DNA cleavage by I is enhanced in the presence of redox
      active species. The in vivo antitumor activity of I is considerable and is
      accompanied by significant elimination of red blood cell and kidney damage.
      Remarkably, compound I in combination with cisplatin (combined Re-Pt antitumor
      system) led to suppression of tumor growth or complete tumor elimination. The
      antihemolytic and nephroprotective abilities of I only or as a part of the Re-Pt
      antitumor system were established and a possible mechanism for the influence of I
      on these properties, involving erythropoietin production, is proposed. 

PMID- 24121303
TI  - Synthesis and in vitro antitumor activity of water soluble sulfonate- and ester
      functionalized silver(I) N-heterocyclic carbene complexes.
AB  - The novel N-heterocyclic carbene ligand precursor NaHIm(PrSO3) (sodium 3,3'-(1H
      imidazole-3-ium-1,3-diyl)dipropane-1-sulfonate) and the related silver carbene
      complex [Na4(Im(PrSO3))2]AgCl have been synthesized and characterized.
      Recrystallization of the analogous [Im(AcEt)]AgCl complex allowed the development
      of X-ray analysis which led to achieve relevant structural information concerning
      this silver(I) derivative. Both sulfonate- and ester-functionalized silver(I) N
      heterocyclic carbenes (NHCs) were evaluated for their antiproliferative
      activities in a wide panel of human cancer cells. Complex [Na4(Im(PrSO3))2]AgCl
      showed a significant in vitro antiproliferative activity that was correlated with
      its strong ability to inhibit thioredoxin reductase. The inhibition of this
      selenoenzyme determined an alteration of the cellular redox environment thus
      leading to the induction of the apoptotic cell death through the activation of
      the ASK-1 pathway. 

PMID- 24121304
TI  - Electrospun TiC/C nano-felt surface-decorated with Pt nanoparticles as highly
      efficient and cost-effective counter electrode for dye-sensitized solar cells.
AB  - Electrospun nano-felt consisting of overlaid TiC/C composite nanofibers was
      surface-decorated with Pt nanoparticles (Pt NPs) for use as highly efficient and
      cost-effective counter electrode (CE) in dye-sensitized solar cells (DSSCs). In
      the nanofibers, the self-generated TiC crystallites (~70 wt%) with sizes of ~20
      nm were randomly embedded in carbon (~30 wt%). Upon surface-decoration, most Pt
      NPs were distributed on TiC crystallites, leading to substantial enhancement in
      the electrocatalytic activity/efficiency of Pt due to the strong interaction
      between Pt and TiC as well as the resulting synergetic effect on
      electrocatalysis. Electrochemical measurements indicated that the TiC/C-Pt CE
      exhibited low charge transfer resistance (Rct), large capacitance (C), and fast
      reaction rate towards the reduction of I3(-) ions, and the prototype DSSC
      exhibited a performance comparable to that with conventional Pt CE in terms of
      short circuit current density (Jsc), open circuit voltage (Voc), fill factor
      (FF), and energy conversion efficiency (eta).

PMID- 24121305
TI  - Binocular vision enhances a rapidly evolving affordance priming effect:
      behavioural and TMS evidence.
AB  - Extensive research has suggested that simply viewing an object can automatically
      prime compatible actions for object manipulation, known as affordances. Here we
      explored the generation of covert motor plans afforded by real objects with
      precision ('pinchable') or whole-hand/power ('graspable') grip significance under
      different types of vision. In Experiment 1, participants viewed real object
      primes either monocularly or binocularly and responded to orthogonal auditory
      stimuli by making precision or power grips. Pinchable primes facilitated
      congruent precision grip responses relative to incongruent power grips, and vice
      versa for graspable primes, but only in the binocular vision condition. To
      examine the temporal evolution of the binocular affordance effect, participants
      in Experiment 2 always viewed the objects binocularly but made no responses,
      instead receiving a transcranial magnetic stimulation pulse over their primary
      motor cortex at three different times (150, 300, 450ms) after prime onset. Motor
      evoked potentials (MEPs) recorded from a pinching muscle were selectively
      increased when subjects were primed with a pinchable object, whereas MEPs from a
      muscle associated with power grips were increased when viewing graspable stimuli.
      This interaction was obtained both 300 and 450ms (but not 150ms) after the visual
      onset of the prime, characterising for the first time the rapid development of
      binocular grip-specific affordances predicted by functional accounts of the
      affordance effect. 

PMID- 24121306
TI  - Caesium-137 distribution, inventories and accumulation history in the Baltic Sea
      sediments.
AB  - The Baltic Sea is susceptible to pollution by hazardous substances due to limited
      water exchange, shallowness, and the large catchment area. Radionuclides,
      particularly (137)Cs, are one of the most hazardous anthropogenic substances
      present in the Baltic environment. This study was conducted to present (137)Cs
      present contamination that should further be a subject of reliable monitoring
      when the new Nuclear Power Plant is put into operation in the northern Poland.
      The sea-wide, up to date distribution of (137)Cs activities and inventories in
      the Baltic Sea bottom sediments are presented. The (137)Cs activity
      concentrations were measured in 30 cm long sediment cores collected at 22
      sampling stations. Sediment accumulation rates were quantified by (210)Pb
      geochronology to follow the history of (137)Cs accumulation. The (137)Cs
      inventories and fluxes were calculated. Most of the Baltic Sea sediments
      accumulated (137)Cs in the range from 750 to 2675 Bq m(-2). The Bothnian Bay is
      severely contaminated by (137)Cs with inventories up to 95,191 Bq m(-2). This
      region is moreover characterized by extremely large patchiness of (137)Cs
      inventories. The (137)Cs annual fluxes are highest at the two stations located at
      the Bothnian Bay (342 Bq m(-2) and 527 Bq m(-2)) due to large Chernobyl (137)Cs
      contamination of that region and high sediment accumulation rates. When these
      stations are excluded, the recent, annual mean value of (137)Cs load to the
      Baltic Sea deposits is 38 +/- 22 Bq m(-2). The distribution of radio-caesium
      inventories over the Baltic Sea nowadays reflects the pattern of Chernobyl
      contamination. The radio-caesium deposited in surface sediments is not
      permanently buried, but may be resuspended and redeposited by currents,
      bioturbation or anthropogenic activities. 

PMID- 24121307
TI  - Internet-based, culturally sensitive, problem-solving therapy for Turkish
      migrants with depression: randomized controlled trial.
AB  - BACKGROUND: Turkish migrants living in the Netherlands have a high prevalence of
      depressive disorders, but experience considerable obstacles to accessing
      professional help. Providing easily accessible Internet treatments may help to
      overcome these barriers. OBJECTIVE: The aim of this study was to evaluate the
      effectiveness of a culturally sensitive, guided, self-help, problem-solving
      intervention through the Internet for reducing depressive symptoms in Turkish
      migrants. METHODS: A two-armed randomized controlled trial was conducted. The
      primary outcome measure was the severity of depressive symptoms; secondary
      outcome measures were somatic symptoms, anxiety, quality of life, and
      satisfaction with the treatment. Participants were assessed online at baseline,
      posttest (6 weeks after baseline), and 4 months after baseline. Posttest results
      were analyzed on the intention-to-treat sample. Missing values were estimated by
      means of multiple imputation. Differences in clinical outcome between groups were
      analyzed with a t test. Cohen's d was used to determine the between-groups effect
      size at posttreatment and follow-up. RESULTS: Turkish adults (N=96) with
      depressive symptoms were randomized to the experimental group (n=49) or to a
      waitlist control group (n=47). High attrition rates were found among the 96
      participants of which 42% (40/96) did not complete the posttest (6 weeks) and 62%
      (59/96) participants did not complete the follow-up assessment at 4 months. No
      significant difference between the experimental group and the control group was
      found for depression at posttest. Recovery occurred significantly more often in
      the experimental group (33%, 16/49) than in the control group (9%, 4/47) at
      posttest (P=.02). Because of the high attrition rate, a completers-only analysis
      was conducted at follow-up. The experimental group showed significant improvement
      in depression compared to the control group both at posttest (P=.01) and follow
      up (P=.01). CONCLUSIONS: The results of this study did not show a significant
      effect on the reduction of depressive symptoms. However, the effect size at
      posttest was high, which might be an indicator of the possible effectiveness of
      the intervention when assessed in a larger sample and robust trial. Future
      research should replicate our study with adequately powered samples. TRIAL
      REGISTRATION: Dutch Trial Register: NTR2303.
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2303 (Archived by
      WebCite at http://www.webcitation.org/6IOxNgoDu).

PMID- 24121308
TI  - Thermoresponsive dendrimers based on oligoethylene glycols: design, synthesis and
      cytotoxic activity against MCF-7 breast cancer cells.
AB  - Three interesting thermoresponsive branched oligoethylene glycol dendrimers based
      on tetrabromohydroquinone were efficiently synthesized from
      tetrabromohydroquinone and three different oligoethylene glycol derivatives. By
      visual inspection, all these dendrimers are water-soluble at room temperature.
      The thermoresponsive behaviors were investigated by using UV/vis turbidity
      measurement at different temperatures for 0.25 wt% of aqueous solutions from D1,
      D2 and D3. The cytotoxicity of the prepared dendrimers was tested against MCF-7
      breast cancer cells. All tested dendrimers showed considerable results, where D2
      dendrimer gave the best result; it showed cytotoxicity against MCF-7 cell line
      with IC50 of 1.07 MUg/mL and resistant fraction equals 1.97%, the other two
      dendrimers showed a modest cytotoxic profile.

PMID- 24121309
TI  - Synthesis and biological activity of mycophenolic acid-amino acid derivatives.
AB  - In search of new immunosuppressants we synthesized 11 amino acids derivatives of
      MPA as methyl esters 10a-k using EDCI/DMAP and their corresponding amino acid
      derivatives in free acid form 11a-k by hydrolysis of ester group with LiOH/MeOH.
      New analogs were evaluated as growth inhibitors of lymphoid cell line (Jurkat)
      and human peripheral blood mononuclear cells (PBMC) from healthy donors.
      According to obtained results recovering of free carboxylic group increased their
      activity. Additionally, the cytotoxic properties depends on the substituent and
      configuration at chiral center in amino acid unit. The compounds 10j, 11e and 11h
      exhibited higher potency than MPA 1 in vitro.

PMID- 24121310
TI  - A new cellular stress response that triggers centriolar satellite reorganization
      and ciliogenesis.
AB  - Centriolar satellites are small, granular structures that cluster around
      centrosomes, but whose biological function and regulation are poorly understood.
      We show that centriolar satellites undergo striking reorganization in response to
      cellular stresses such as UV radiation, heat shock, and transcription blocks,
      invoking acute and selective displacement of the factors AZI1/CEP131, PCM1, and
      CEP290 from this compartment triggered by activation of the stress-responsive
      kinase p38/MAPK14. We demonstrate that the E3 ubiquitin ligase MIB1 is a new
      component of centriolar satellites, which interacts with and ubiquitylates AZI1
      and PCM1 and suppresses primary cilium formation. In response to cell stress,
      MIB1 is abruptly inactivated in a p38-independent manner, leading to loss of
      AZI1, PCM1, and CEP290 ubiquitylation and concomitant stimulation of
      ciliogenesis, even in proliferating cells. Collectively, our findings uncover a
      new two-pronged signalling response, which by coupling p38-dependent
      phosphorylation with MIB1-catalysed ubiquitylation of ciliogenesis-promoting
      factors plays an important role in controlling centriolar satellite status and
      key centrosomal functions in a cell stress-regulated manner. 

PMID- 24121312
TI  - Correlation of (18)F-fluoromisonidazole PET findings with HIF-1alpha and p53
      expressions in head and neck cancer: comparison with (18)F-FDG PET.
AB  - OBJECTIVE: We evaluated tumor hypoxia using F-fluoromisonidazole (F-FMISO) PET in
      relation to the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and
      p53 in patients with head and neck cancer and compared the results with those
      obtained using 2-deoxy-2-F-fluoro-D-glucose (F-FDG) PET. MATERIALS AND METHODS: A
      total of 28 tumors (23 primary tumors and five metastatic lymph nodes) from 24
      patients with newly diagnosed head and neck cancer were examined with F-FMISO PET
      and F-FDG PET. The F-FMISO PET images were scaled to the venous blood
      concentration of F-FMISO activity to produce tumor-to-blood (T/B) values. Hypoxia
      was defined as a region with a T/B ratio greater than or equal to 1.2. The
      maximum T/B (T/Bmax) and hypoxic volumes were calculated by region-of-interest
      analysis. For F-FDG PET, the maximum standardized uptake value (SUVmax) and
      hypermetabolic volume were calculated by region-of-interest analysis. The
      expressions of HIF-1alpha and p53 using immunohistochemistry were estimated in
      tumor tissue samples. RESULTS: A weak correlation was observed between hypoxic
      volume and T/Bmax (r=0.53, P=0.003) on using F-FMISO PET and between
      hypermetabolic volume and SUVmax (r=0.38, P=0.046) on using F-FDG PET. The
      hypoxic volume using F-FMISO PET and hypermetabolic volume using F-FDG PET also
      showed a weak correlation (r=0.44, P=0.020). The values of F-FMISO hypoxic volume
      showed a weak correlation with HIF-1alpha (r=0.40, P=0.037) and p53 (r=0.47,
      P=0.012) obtained on immunohistochemical examination. CONCLUSION: This study
      demonstrates a weak correlation between hypoxic volume measured by F-FMISO PET
      and expressions of HIF-1alpha and p53 in head and neck cancer.

PMID- 24121311
TI  - The MADS transcription factor XAL2/AGL14 modulates auxin transport during
      Arabidopsis root development by regulating PIN expression.
AB  - Elucidating molecular links between cell-fate regulatory networks and dynamic
      patterning modules is a key for understanding development. Auxin is important for
      plant patterning, particularly in roots, where it establishes positional
      information for cell-fate decisions. PIN genes encode plasma membrane proteins
      that serve as auxin efflux transporters; mutations in members of this gene family
      exhibit smaller roots with altered root meristems and stem-cell patterning.
      Direct regulators of PIN transcription have remained elusive. Here, we establish
      that a MADS-box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN
      transcriptional regulation during Arabidopsis root development; mutations in this
      gene exhibit altered stem-cell patterning, root meristem size, and root growth.
      XAL2 is necessary for normal shootward and rootward auxin transport, as well as
      for maintaining normal auxin distribution within the root. Furthermore, this MADS
      domain transcription factor upregulates PIN1 and PIN4 by direct binding to
      regulatory regions and it is required for PIN4-dependent auxin response. In turn,
      XAL2 expression is regulated by auxin levels thus establishing a positive
      feedback loop between auxin levels and PIN regulation that is likely to be
      important for robust root patterning. 

PMID- 24121313
TI  - Clinical value of technetium-99m-labeled octreotide scintigraphy in local
      recurrent or metastatic medullary thyroid cancers: a comparison of lesions with
      18F-FDG-PET and MIBI images.
AB  - AIM: Various studies have been conducted for determining the most optimal method
      for the early diagnosis of local recurrent or distant metastatic thyroid cancers.
      The aim of this study was to evaluate the clinical utility of technetium-99m (Tc
      99m)-labeled octreotide derivatives in the detection of recurrence or distant
      metastases in medullary thyroid cancer patients and to compare the lesions with
      those detected using 18F-fluorodeoxyglucose (18F-FDG)-PET and Tc-99m MIBI studies
      in the same patient group. PATIENTS AND METHODS: Sixteen medullary thyroid cancer
      patients [two male and 14 female; mean age 52.0 +/- 14.1 years (range 13-72
      years)] were included in this study. All patients underwent a whole-body scan 1
      and 4 h after injection with octreotide derivatives and single photon emission
      computed tomography images were taken of the sites suspicious for metastasis. The
      lesions seen in Tc-99m HYNIC octreotide studies were compared with those seen in
      18F-FDG-PET and Tc-99m MIBI studies. RESULTS: Among the Tc-99m-labeled octreotide
      scintigraphy studies, nine were evaluated as true positive (56.2%) and one was
      evaluated as false positive (6.2%); six were false negative (37.5%). In 16
      patients, the total number of lesions seen on octreotide scintigraphy was 21.
      Thirteen of the 16 patients underwent 18F-FDG-PET imaging. Of the 13 patients
      studied, 10 showed true-positive (76.9%) and three showed false-negative (23.1%)
      results. The total number of lesions seen on 18F-FDG-PET was 23. The Tc-99m MIBI
      study yielded positive results in seven of 16 patients (43.7%) and negative
      results in nine patients (56.3%). The total number of lesions on Tc-99m MIBI was
      12. CONCLUSION: The Tc-99m-labeled somatostatin receptor scintigraphy analogs
      HYNIC-tyrosine octreotide and HYNIC-TATE are useful imaging alternatives in
      somatostatin receptor-expressing thyroid cancers. Radiolabeling using these
      analogs is easy and they are readily available for routine use.

PMID- 24121316
TI  - A folding transition underlies the emergence of membrane affinity in amyloid
      beta.
AB  - Small amyloid-beta (Abeta) oligomers have much higher membrane affinity compared
      to the monomers, but the structural origin of this functional change is not
      understood. We show that as monomers assemble into small n-mers (n < 10), Abeta
      acquires a tertiary fold that is consistent with the mature fibrils. This is an
      early and defining transition for the aggregating peptide, and possibly underpins
      its altered bioactivity. 

PMID- 24121317
TI  - [Undislocated fracture of cuneiform I bone complicated by language barrier].
AB  - A 30-year-old non-German speaking patient suffered an ankle sprain while playing
      beach volleyball. Conventional radiography did not reveal any fractures. The
      patient was treated with a Geisha cast for immobilization and relief and was also
      informed about pain-dependent weight bearing using an illustrated information
      sheet. In the course of the healing process the patient consulted the orthopedic
      department a second time. During a third visit he left before consultation as he
      felt that the waiting time was too long. Because he disagreed with the treatment
      he visited an orthopedist who ordered a magnetic resonance imaging (MRI) scan of
      the patient's foot. The MRI scan revealed an undislocated fracture of the
      cuneiform I bone. A control scan was conducted 2 months later and complex
      regional pain syndrome (CRPS) was diagnosed. The orthopedist ordered treatment
      based on a therapy with a VacoPed(r) orthesis. When there was no improvement in
      the healing process the patient sued the orthopedic surgeon for medical
      malpractice due to incorrect load and subsequent pain for ? 40,000. All courts up
      to the Federal Court of Germany dismissed the case as no expert witnesses could
      find any errors in treatment. The court held that the medical information of the
      non-German speaking patient was sufficient against the defendant's arguments. It
      is, however, noteworthy that the burden of proof for sufficient medical
      information of a patient is always placed on the treating physician.

PMID- 24121318
TI  - Chemical reduction of graphene oxide: a synthetic chemistry viewpoint.
AB  - The chemical reduction of graphene oxide is a promising route towards the large
      scale production of graphene for commercial applications. The current state-of
      the-art in graphene oxide reduction, consisting of more than 50 types of reducing
      agent, will be reviewed from a synthetic chemistry point of view. Emphasis is
      placed on the techniques, reaction mechanisms and the quality of the produced
      graphene. The reducing agents are reviewed under two major categories: (i) those
      which function according to well-supported mechanisms and (ii) those which
      function according to proposed mechanisms based on knowledge of organic
      chemistry. This review will serve as a valuable platform to understand the
      efficiency of these reducing agents for the reduction of graphene oxide. 

PMID- 24121319
TI  - Diffraction structural biology - a new horizon.
AB  - An introductory overview to the special issue papers on diffraction structural
      biology in this issue of the journal. 

PMID- 24121320
TI  - Sub-millisecond time-resolved SAXS using a continuous-flow mixer and X-ray
      microbeam.
AB  - Small-angle X-ray scattering (SAXS) is a well established technique to probe the
      nanoscale structure and interactions in soft matter. It allows one to study the
      structure of native particles in near physiological environments and to analyze
      structural changes in response to variations in external conditions. The
      combination of microfluidics and SAXS provides a powerful tool to investigate
      dynamic processes on a molecular level with sub-millisecond time resolution.
      Reaction kinetics in the sub-millisecond time range has been achieved using
      continuous-flow mixers manufactured using micromachining techniques. The time
      resolution of these devices has previously been limited, in part, by the X-ray
      beam sizes delivered by typical SAXS beamlines. These limitations can be overcome
      using optics to focus X-rays to the micrometer size range providing that beam
      divergence and photon flux suitable for performing SAXS experiments can be
      maintained. Such micro-SAXS in combination with microfluidic devices would be an
      attractive probe for time-resolved studies. Here, the development of a high-duty
      cycle scanning microsecond-time-resolution SAXS capability, built around the
      Kirkpatrick-Baez mirror-based microbeam system at the Biophysics Collaborative
      Access Team (BioCAT) beamline 18ID at the Advanced Photon Source, Argonne
      National Laboratory, is reported. A detailed description of the microbeam small
      angle-scattering instrument, the turbulent flow mixer, as well as the data
      acquisition and control and analysis software is provided. Results are presented
      where this apparatus was used to study the folding of cytochrome c. Future
      prospects for this technique are discussed.

PMID- 24121321
TI  - Cryo-electron tomography: moving towards revealing the viral life cycle of Rice
      dwarf virus.
AB  - It is well known that viruses utilize the host cellular systems for their
      infection and replication processes. However, the molecular mechanisms underlying
      these processes are poorly understood for most viruses. To understand these
      molecular mechanisms, it is essential to observe the viral and virus-related
      structures and analyse their molecular interactions within a cellular context.
      Cryo-electron microscopy and tomography offer the potential to observe
      macromolecular structures and to analyse their molecular interactions within the
      cell. Here, using cryo-electron microscopy and tomography, the structures of Rice
      dwarf virus are reported within fully hydrated insect vector cells grown on
      electron microscopy grids towards revealing the viral infection and replication
      mechanisms. 

PMID- 24121322
TI  - U-shape rotating anti-cathode compact X-ray generator: 20 times stronger than the
      commercially available X-ray source.
AB  - A new type of U-shape anti-cathode X-ray generator in which the inner surface of
      a cylindrical target is irradiated by an electron beam has been made by modifying
      a conventional rotating anti-cathode X-ray generator whose brightness in the
      catalog is 12 kW mm(-2). The target material (Cu), target radius (50 mm) and
      rotating speed (6,000 r.p.m.) were not changed in this modification. A brightness
      of 52 kW mm(-2) was obtained by this U-shape-type X-ray generator. This means
      that the brightness of the new type is 4.3 times greater than that of the old
      unmodified one. Furthermore, the new-type X-ray generator yielded a brightness of
      129 kW mm(-2) by adding a carbon coating on the Cu target. This means an overall
      increase of brightness of ten times. The original generator has the highest
      brightness in the generators of the same class (having a radius of 50 mm and
      rotation speed of 6,000 r.p.m.). Observations showed that Cu Kalpha counts at
      vertical incidence of the electron beam onto the surface of the new target, which
      is initially optically smooth, decrease as the surface is roughened by a severe
      thermal stress caused by strong electron beam exposure. Further observation
      reveals, however, that oblique incidence of the electron beam onto the roughened
      surface drastically increased the X-ray output and amounts to twice as much as
      that from a smooth surface at vertical incidence. Thus, at the present stage, an
      overall increase of brightness has been realised at a level 20 times stronger
      than that of the original commercially offered X-ray generator that we modified.

PMID- 24121323
TI  - Hydrogen-bond network and pH sensitivity in human transthyretin.
AB  - Transthyretin (TTR) is a tetrameric protein. TTR misfolding and aggregation are
      associated with human amyloid diseases. Dissociation of the TTR tetramer is
      believed to be the rate-limiting step in the amyloid fibril formation cascade.
      Low pH is known to promote dissociation into monomer and the formation of amyloid
      fibrils. In order to reveal the molecular mechanisms underlying pH sensitivity
      and structural stabilities of TTR, neutron diffraction studies were conducted
      using the IBARAKI Biological Crystal Diffractometer with the time-of-flight
      method. Crystals for the neutron diffraction experiments were grown up to 2.5
      mm(3) for four months. The neutron crystal structure solved at 2.0 A revealed the
      protonation states of His88 and the detailed hydrogen-bond network depending on
      the protonation states of His88. This hydrogen-bond network is involved in
      monomer-monomer and dimer-dimer interactions, suggesting that the double
      protonation of His88 by acidification breaks the hydrogen-bond network and causes
      the destabilization of the TTR tetramer. Structural comparison with the X-ray
      crystal structure at acidic pH identified the three amino acid residues
      responsible for the pH sensitivity of TTR. Our neutron model provides insights
      into the molecular stability related to amyloidosis.

PMID- 24121324
TI  - New methodologies at PF AR-NW12A: the implementation of high-pressure
      macromolecular crystallography.
AB  - The macromolecular crystallography (MX) beamline AR-NW12A is evolving from its
      original design of high-throughput crystallography to a multi-purpose end
      station. Among the various options to be implemented, great efforts were made in
      making available high-pressure MX (HPMX) at the beamline. High-pressure molecular
      biophysics is a developing field that attracts the interest of a constantly
      growing scientific community. A plethora of activities can benefit from high
      pressure, and investigations have been performed on its applicability to study
      multimeric complex assemblies, compressibility of proteins and their crystals,
      macromolecules originating from extremophiles, or even the trapping of higher
      energy conformers for molecules of biological interest. Recent studies using HPMX
      showed structural hydrostatic-pressure-induced changes in proteins. The
      conformational modifications could explain the enzymatic mechanism differences
      between proteins of the same family, living at different environmental pressures,
      as well as the initial steps in the pressure-denaturation process that have been
      attributed to water penetration into the protein interior. To facilitate further
      HPMX, while allowing access to various individualized set-ups and experiments,
      the AR-NW12A sample environment has been revisited. Altogether, the newly added
      implementations will bring a fresh breath of life to AR-NW12A and allow the MX
      community to experiment in a larger set of fields related to structural biology. 

PMID- 24121325
TI  - Structural studies of haemoglobin from pisces species shortfin mako shark (Isurus
      oxyrinchus) at 1.9 A resolution.
AB  - Haemoglobin (Hb) is a tetrameric iron-containing protein that carries oxygen from
      the lungs to tissues and carbon dioxide from tissues back to the lungs. Pisces
      are the advanced aquatic vertebrates capable of surviving at wide depth ranges.
      The shortfin mako shark (SMS) is the pelagic, largest, fastest and most
      sophisticated species of the shark kingdom with well developed eyes. Mostly the
      pisces species are cold blooded in nature. Distinctly, the SMSs are warm-blooded
      animals with an advanced circulatory system. SMSs are capable of maintaining
      elevated muscle temperatures up to 33 K above the ambient water temperatures at a
      depth of 150-500 m. SMSs have a diverged air-breathing mechanism compared with
      other vertebrates. The haemoglobin molecule consists of four polypeptide chains,
      namely two alpha chains, each with 140 amino acids and two beta chains each
      having 136 amino acids. The SMS Hb was found to crystallize in monoclinic space
      group P21 using the hanging-drop vapour-diffusion method at room temperature. The
      crystal packing parameters for the SMS Hb structure contain one whole biological
      molecule in the asymmetric unit with a solvent content of 47%. The SMS Hb
      quaternary structural features interface-interface interactions and heme binding
      sites are discussed with different state Hbs and the results reveal that SMS Hb
      adopts an unliganded deoxy T state conformation.

PMID- 24121326
TI  - Morphological image processing for quantitative shape analysis of biomedical
      structures: effective contrast enhancement.
AB  - Image processing methods significantly contribute to visualization of images
      captured by biomedical modalities (such as mammography, X-ray computed
      tomography, magnetic resonance imaging, and light and electron microscopy).
      Quantitative interpretation of the deluge of complicated biomedical images,
      however, poses many research challenges, one of which is to enhance structural
      features that are scarcely perceptible to the human eye. This study introduces a
      contrast enhancement approach based on a new type of mathematical morphology
      called rotational morphological processing. The proposed method is applied to
      medical images for the enhancement of structural features. The effectiveness of
      the method is evaluated quantitatively by the contrast improvement ratio (CIR).
      The CIR of the proposed method is 12.1, versus 4.7 and 0.1 for two conventional
      contrast enhancement methods, clearly indicating the high contrasting capability
      of the method. 

PMID- 24121327
TI  - Crystal structure analysis, overexpression and refolding behaviour of a DING
      protein with single mutation.
AB  - After crystallization of a certain protein-RNA complex, well diffracting crystals
      were obtained. However, the asymmetric unit of the crystal was too small to
      locate any components. Mass spectrometry and X-ray crystal structure analysis
      showed that it was a member of the DING protein family (HPBP). Surprisingly, the
      structure of HPBP reported previously was also determined accidentally as a
      contaminant, suggesting that HPBP has a strong tendency to crystallize.
      Furthermore, DING proteins were reported to relate in disease. These observations
      suggest that DING has potential for application in a wide range of research
      fields. To enable further analyses, a system for preparation of HPBP was
      constructed. As HPBP was expressed in insoluble form in Escherichia coli, it was
      unfolded chemically and refolded. Finally, a very high yield preparation method
      was constructed, in which 43 mg of HPBP was obtained from 1 L of culture.
      Furthermore, to evaluate the validity of refolding, its crystal structure was
      determined at 1.03 A resolution. The determined structure was identical to the
      native structure, in which two disulfide bonds were recovered correctly and a
      phosphate ion was captured. Based on these results, it was concluded that the
      refolded HPBP recovers its structure correctly.

PMID- 24121328
TI  - Phase-diagram-guided method for growth of a large crystal of glycoside hydrolase
      family 45 inverting cellulase suitable for neutron structural analysis.
AB  - Neutron protein crystallography (NPC) is a powerful tool for determining the
      hydrogen position and water orientation in proteins, but a much larger protein
      crystal is needed for NPC than for X-ray crystallography, and thus crystal
      preparation is a bottleneck. To obtain large protein crystals, it is necessary to
      know the properties of the target protein in the crystallization solution. Here,
      a crystal preparation method of fungal cellulase PcCel45A is reported, guided by
      the phase diagram. Nucleation and precipitation conditions were determined by
      sitting-drop vapor diffusion. Saturation and unsaturation conditions were
      evaluated by monitoring crystal dissolution, and a crystallization phase diagram
      was obtained. To obtain a large crystal, crystallization solution was prepared on
      a sitting bridge (diameter = 5 mm). Initial crystallization conditions were 40 ul
      of crystallization solution (40 mg ml(-1) protein with 30.5% 3-methyl-1,5
      pentanediol in 50 mM tris-HCl pH 8.0) with a 1,000 ul reservoir (61% 3-methyl
      1,5,-pentanediol in 50 mM tris-HCl pH 8.0) at 293 K. After the first crystal
      appeared, the concentration of precipitant in the reservoir solution was reduced
      to 60% to prevent formation of further crystals. Finally, we obtained a crystal
      of 6 mm(3) volume (3 mm * 2 mm * 1 mm), which was suitable for neutron
      diffraction.

PMID- 24121329
TI  - Structural fluctuation observed in Z-DNA d(CGCGCG)2 in the absence of divalent
      metal cations and polyamines.
AB  - In the present study, Z-DNA d(CGCGCG)2 was crystallized from a DNA solution in
      the absence of divalent metal cations and polyamines, and its X-ray structure was
      determined at 0.98 A resolution. Comparison of this structure and previously
      reported Z-DNA structures, containing Mg(2+) cations and/or polyamines,
      demonstrated that Z-DNA can have structural fluctuations with respect to
      phosphate groups and hydration in the minor groove. At the GpC steps, a two-state
      structural equilibrium between the ZI and ZII conformations was frequently
      observed. In contrast, at the CpG steps, the phosphate groups exhibited
      rotational fluctuation, which could induce distortion of sugar puckering. In
      addition, alternative positions of water molecules were found in the middle of
      the minor groove of the Z-DNA. These structural fluctuations were likely
      observable because of the absence of Mg(2+) cations and polyamines. The results
      related to these phenomena were supported by those of other experimental methods,
      suggesting the possibility of these fluctuations occurring in biological
      conditions.

PMID- 24121330
TI  - Structure of liposome encapsulating proteins characterized by X-ray scattering
      and shell-modeling.
AB  - Lipid liposomes are promising drug delivery systems because they have superior
      curative effects owing to their high adaptability to a living body. Lipid
      liposomes encapsulating proteins were constructed and the structures examined
      using synchrotron radiation small- and wide-angle X-ray scattering (SR-SWAXS).
      The liposomes were prepared by a sequential combination of natural swelling,
      ultrasonic dispersion, freeze-throw, extrusion and spin-filtration. The liposomes
      were composed of acidic glycosphingolipid (ganglioside), cholesterol and
      phospholipids. By using shell-modeling methods, the asymmetric bilayer structure
      of the liposome and the encapsulation efficiency of proteins were determined. As
      well as other analytical techniques, SR-SWAXS and shell-modeling methods are
      shown to be a powerful tool for characterizing in situ structures of lipid
      liposomes as an important candidate of drug delivery systems.

PMID- 24121331
TI  - X-ray structure determination and deuteration of nattokinase.
AB  - Nattokinase (NK) is a strong fibrinolytic enzyme, which is produced in abundance
      by Bacillus subtilis natto. Although NK is a member of the subtilisin family, it
      displays different substrate specificity when compared with other subtilisins.
      The results of molecular simulations predict that hydrogen arrangements around
      Ser221 at the active site probably account for the substrate specificity of NK.
      Therefore, neutron crystallographic analysis should provide valuable information
      that reveals the enzymatic mechanism of NK. In this report, the X-ray structure
      of the non-hydrogen form of undeuterated NK was determined, and the preparation
      of deuterated NK was successfully achieved. The non-hydrogen NK structure was
      determined at 1.74 A resolution. The three-dimensional structures of NK and
      subtilisin E from Bacillus subtilis DB104 are near identical. Deuteration of NK
      was carried out by cultivating Bacillus subtilis natto in deuterated medium. The
      D2O resistant strain of Bacillus subtilis natto was obtained by successive
      cultivation rounds, in which the concentration of D2O in the medium was gradually
      increased. NK was purified from the culture medium and its activity was confirmed
      by the fibrin plate method. The results lay the framework for neutron protein
      crystallography analysis.

PMID- 24121332
TI  - Experiences with archived raw diffraction images data: capturing cisplatin after
      chemical conversion of carboplatin in high salt conditions for a protein crystal.
AB  - The archiving of raw diffraction images data is the focus of an IUCr Diffraction
      Data Deposition Working Group (see http://forums.iucr.org/). Experience in
      archiving and sharing of raw diffraction images data in collaboration between
      Manchester and Utrecht Universities, studying the binding of the important anti
      cancer agents, cisplatin and carboplatin to histidine in a protein, has recently
      been published. Subsequently, these studies have been expanded due to further
      analyses of each data set of raw diffraction images using the diffraction data
      processing program XDS. The raw diffraction images, measured at Manchester
      University, are available for download at Utrecht University and now also
      mirrored at the Tardis Raw Diffraction Data Archive in Australia. Thus a direct
      comparison of processed diffraction and derived protein model data from XDS with
      the published results has been made. The issue of conversion of carboplatin to
      cisplatin under a high chloride salt concentration has been taken up and a
      detailed crystallographic assessment is provided. Overall, these new structural
      chemistry research results are presented followed by a short summary of
      developing raw data archiving policy and practicalities as well as documenting
      the challenge of making appropriate and detailed recording of the metadata for
      crystallography. 

PMID- 24121333
TI  - Crystal structure of endo-1,4-beta-glucanase from Eisenia fetida.
AB  - The saccharification process is essential for bioethanol production from woody
      biomass including celluloses. Cold-adapted cellulase, which has sufficient
      activity at low temperature (<293 K), is capable of reducing heating costs during
      the saccharification process and is suitable for simultaneous saccharification
      and fermentation. Endo-1,4-beta-glucanase from the earthworm Eisenia fetida (EF
      EG2) belonging to glycoside hydrolase family 9 has been shown to have the highest
      activity at 313 K, and also retained a comparatively high activity at 283 K. The
      recombinant EF-EG2 was purified expressed in Pichia pastoris, and then grew
      needle-shaped crystals with dimensions of 0.02 * 0.02 * 1 mm. The crystals
      belonged to the space group P3221 with unit-cell parameters of a = b = 136 A, c =
      55.0 A. The final model of EF-EG2, including 435 residues, two ions, seven
      crystallization reagents and 696 waters, was refined to a crystallographic R
      factor of 14.7% (free R-factor of 16.8%) to 1.5 A resolution. The overall
      structure of EF-EG2 has an (alpha/alpha)6 barrel fold which contains a putative
      active-site cleft and a negatively charged surface. This structural information
      helps us understand the catalytic and cold adaptation mechanisms of EF-EG2.

PMID- 24121334
TI  - Improvement of an automated protein crystal exchange system PAM for high
      throughput data collection.
AB  - Photon Factory Automated Mounting system (PAM) protein crystal exchange systems
      are available at the following Photon Factory macromolecular beamlines: BL-1A, BL
      5A, BL-17A, AR-NW12A and AR-NE3A. The beamline AR-NE3A has been constructed for
      high-throughput macromolecular crystallography and is dedicated to structure
      based drug design. The PAM liquid-nitrogen Dewar can store a maximum of three
      SSRL cassettes. Therefore, users have to interrupt their experiments and replace
      the cassettes when using four or more of them during their beam time. As a result
      of investigation, four or more cassettes were used in AR-NE3A alone. For
      continuous automated data collection, the size of the liquid-nitrogen Dewar for
      the AR-NE3A PAM was increased, doubling the capacity. In order to check the
      calibration with the new Dewar and the cassette stand, calibration experiments
      were repeatedly performed. Compared with the current system, the parameters of
      the novel system are shown to be stable.

PMID- 24121335
TI  - Crystal structure of UDP-glucose:anthocyanidin 3-O-glucosyltransferase from
      Clitoria ternatea.
AB  - Flowers of the butterfly pea (Clitoria ternatea) accumulate a group of
      polyacylated anthocyanins, named ternatins, in their petals. The first step in
      ternatin biosynthesis is the transfer of glucose from UDP-glucose to
      anthocyanidins such as delphinidin, a reaction catalyzed in C. ternatea by UDP
      glucose:anthocyanidin 3-O-glucosyltransferase (Ct3GT-A; AB185904). To elucidate
      the structure-function relationship of Ct3GT-A, recombinant Ct3GT-A was expressed
      in Escherichia coli and its tertiary structure was determined to 1.85 A
      resolution by using X-ray crystallography. The structure of Ct3GT-A shows a
      common folding topology, the GT-B fold, comprised of two Rossmann-like
      beta/alpha/beta domains and a cleft located between the N- and C-domains
      containing two cavities that are used as binding sites for the donor (UDP-Glc)
      and acceptor substrates. By comparing the structure of Ct3GT-A with that of the
      flavonoid glycosyltransferase VvGT1 from red grape (Vitis vinifera) in complex
      with UDP-2-deoxy-2-fluoro glucose and kaempferol, locations of the catalytic His
      Asp dyad and the residues involved in recognizing UDP-2-deoxy-2-fluoro glucose
      were essentially identical in Ct3GT-A, but certain residues of VvGT1 involved in
      binding kaempferol were found to be substituted in Ct3GT-A. These findings are
      important for understanding the differentiation of acceptor-substrate recognition
      in these two enzymes.

PMID- 24121336
TI  - High-speed classification of coherent X-ray diffraction patterns on the K
      computer for high-resolution single biomolecule imaging.
AB  - Single-particle coherent X-ray diffraction imaging using an X-ray free-electron
      laser has the potential to reveal the three-dimensional structure of a biological
      supra-molecule at sub-nanometer resolution. In order to realise this method, it
      is necessary to analyze as many as 1 * 10(6) noisy X-ray diffraction patterns,
      each for an unknown random target orientation. To cope with the severe quantum
      noise, patterns need to be classified according to their similarities and average
      similar patterns to improve the signal-to-noise ratio. A high-speed scalable
      scheme has been developed to carry out classification on the K computer, a
      10PFLOPS supercomputer at RIKEN Advanced Institute for Computational Science. It
      is designed to work on the real-time basis with the experimental diffraction
      pattern collection at the X-ray free-electron laser facility SACLA so that the
      result of classification can be feedback for optimizing experimental parameters
      during the experiment. The present status of our effort developing the system and
      also a result of application to a set of simulated diffraction patterns is
      reported. About 1 * 10(6) diffraction patterns were successfully classificatied
      by running 255 separate 1 h jobs in 385-node mode.

PMID- 24121337
TI  - Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor
      TEI-I01800: insight into the selectivity.
AB  - Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is
      a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway
      and plays an important role in inflammatory diseases. The crystal structure of
      the MK2-TEI-I01800 complex has been reported; its Gly-rich loop was found to form
      an alpha-helix, not a beta-sheet as has been observed for other Ser/Thr kinases.
      TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to
      understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2
      (CDK2) complex structure with TEI-I01800 was determined at 2.0 A resolution.
      Interestingly, the Gly-rich loop of CDK2 formed a beta-sheet that was different
      from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly
      rich loop from a beta-sheet to an alpha-helix by collision between Leu70 and a p
      ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI
      I01800 bound to CDK2 without this structural change and lost the interaction with
      the substituent at the 7-position. In summary, the results of this study suggest
      that the reason for the selectivity of TEI-I01800 is the favourable conformation
      of TEI-I01800 itself, making it suitable for binding to the alpha-form MK2.

PMID- 24121338
TI  - SPring-8 BL41XU, a high-flux macromolecular crystallography beamline.
AB  - SPring-8 BL41XU is a high-flux macromolecular crystallography beamline using an
      in-vacuum undulator as a light source. The X-rays are monochromated by a liquid
      nitrogen-cooling Si double-crystal monochromator, and focused by Kirkpatrick-Baez
      mirror optics. The focused beam size at the sample is 80 um (H) * 22 um (V) with
      a photon flux of 1.1 * 10(13) photons s(-1). A pinhole aperture is used to
      collimate the beam in the range 10-50 um. This high-flux beam with variable size
      provides opportunities not only for micro-crystallography but also for data
      collection effectively making use of crystal volume. The beamline also provides
      high-energy X-rays covering 20.6-35.4 keV which allows ultra-high-resolution data
      to be obtained and anomalous diffraction using the K-edge of Xe and I. Upgrade of
      BL41XU for more rapid and accurate data collection is proceeding. Here, details
      of BL41XU are given and an outline of the upgrade project is documented.

PMID- 24121339
TI  - Crystal structure of a complex of human chymase with its benzimidazole derived
      inhibitor.
AB  - The crystal structure of human chymase complexed with a novel benzimidazole
      inhibitor, TJK002, was determined at 2.8 A resolution. The X-ray crystallographic
      study shows that the benzimidazole inhibitor forms a non-covalent interaction
      with the catalytic domain of human chymase. The hydrophobic fragment of the
      inhibitor occupies the S1 pocket. The carboxylic acid group of the inhibitor
      forms hydrogen bonds with the imidazole N(E) atom of His57 and/or the O(gamma)
      atom of Ser195 which are members of the catalytic triad. This imidazole ring of
      His57 induces pi-pi stacking to the benzene ring of the benzimidazole scaffold as
      P2 moiety. Fragment molecular orbital calculation of the atomic coordinates by X
      ray crystallography shows that this imidazole ring of His57 could be protonated
      with the carboxyl group of Asp102 or hydroxyl group of Ser195 and the stacking
      interaction is stabilized. A new drug design strategy is proposed where the
      stacking to the protonated imidazole of the drug target protein with the
      benzimidazole scaffold inhibitor causes unpredicted potent inhibitory activity
      for some enzymes.

PMID- 24121340
TI  - Modulation of the intermolecular interaction of myoglobin by removal of the heme.
AB  - Toward understanding intermolecular interactions governing self-association of
      proteins, the present study investigated a model protein, myoglobin, using a
      small-angle X-ray scattering technique. It has been known that removal of the
      heme makes myoglobin aggregation-prone. The interparticle interferences of the
      holomyoglobin and the apomyoglobin were compared in terms of the structure
      factor. Analysis of the structure factor using a model potential of Derjaguin
      Laudau-Verwey-Overbeek (DLVO) suggests that the intermolecular interaction
      potential of apomyoglobin is more attractive than that of holomyoglobin at short
      range from the protein molecule.

PMID- 24121341
TI  - Structure of the human-heart fatty-acid-binding protein 3 in complex with the
      fluorescent probe 1-anilinonaphthalene-8-sulphonic acid.
AB  - Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein
      abundantly found in cardiomyocytes, plays a role in trafficking fatty acids
      throughout cellular compartments by reversibly binding intracellular fatty acids
      with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8
      sulfonate (ANS) is extensively utilized for examining the interaction of ligands
      with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in
      the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore,
      four water molecules were clearly identified in the binding cavity. Through these
      water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions
      with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67%
      sequence identity with FABP3 and its crystal structure is almost the same as that
      of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To
      understand the difference in their ligand specificities, a structural comparison
      was performed between FABP3-ANS and FABP4-ANS complexes. The result revealed that
      the orientation of ANS binding to FABP3 is completely opposite to that of ANS
      binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may
      result in greater steric hindrance between the side-chain of Leu115 and the
      aniline ring of ANS.

PMID- 24121342
TI  - A docking study of enhanced intracellular survival protein from Mycobacterium
      tuberculosis with human DUSP16/MKP-7.
AB  - The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis,
      and one of its secreted effector proteins, called enhanced intracellular survival
      (Eis) protein, enhances its survival in macrophages. Mtb Eis activates JNK
      specific dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated
      protein kinase phosphatase-7 (MKP-7) through the acetylation on Lys55, thus
      inactivating JNK by dephosphorylation. Based on the recently reported crystal
      structure of Mtb Eis, a docking model for the binding of Mtb Eis to DUSP16/MKP-7
      was generated. In the docking model, the substrate helix containing Lys55 of
      DUSP16/MKP-7 fits nicely into the active-site cleft of Mtb Eis; the twisted beta
      sheet of Eis domain II embraces the substrate helix from one side. Most
      importantly, the side-chain of Lys55 is inserted toward acetyl-CoA and the
      resulting distance is 4.6 A between the NZ atom of Lys55 and the carbonyl carbon
      of the acetyl group in acetyl-CoA. The binding of Mtb Eis and DUSP16/MKP-7 is
      maintained by strong electrostatic interactions. The active-site cleft of Mtb Eis
      has a negatively charged surface formed by Asp25, Glu138, Asp286, Glu395 and the
      terminal carboxylic group of Phe396. In contrast, DUSP16/MKP-7 contains five
      basic residues, Lys52, Lys55, Arg56, Arg57 and Lys62, which point toward the
      negatively charged surface of the active-site pocket of Mtb Eis. Thus, the
      current docking model suggests that the binding of DUSP16/MKP-7 to Mtb Eis should
      be established by charge complementarity in addition to a very favorable
      geometric arrangement. The suggested mode of binding requires the dissociation of
      the hexameric Mtb Eis into dimers or monomers. This study may be useful for
      future studies aiming to develop inhibitors of Mtb Eis as a new anti-tuberculosis
      drug candidate.

PMID- 24121343
TI  - Structural and biochemical analysis of a thermostable membrane-bound stomatin
      specific protease.
AB  - Membrane-bound proteases are involved in various regulatory functions. The N
      terminal region of PH1510p (1510-N) from the hyperthermophilic archaeon
      Pyrococcus horikoshii is a serine protease with a catalytic Ser-Lys dyad (Ser97
      and Lys138), and specifically cleaves the C-terminal hydrophobic region of the p
      stomatin PH1511p. In a form of human hemolytic anemia known as hereditary
      stomatocytosis, the stomatin protein is deficient in the erythrocyte membrane due
      to mis-trafficking. In order to understand the catalytic mechanism of 1510-N in
      more detail, here the structural and biochemical analysis of 1510-N is reported.
      Two degraded products were produced via acyl-enzyme intermediates. 1510-N is a
      thermostable protease, and thus crystallization after heat treatment of the
      protease-peptide complex was attempted in order to understand the catalytic
      mechanism of 1510-N. The structure after heat treatment is almost identical to
      that with no heat treatment. According to the superposition between the
      structures with heat treatment and with no heat treatment, the N-terminal half of
      the peptide is superposed well, whereas the C-terminal half of the peptide is
      slightly deviated. The N-terminal half of the peptide binds to 1510-N more
      tightly than the C-terminal half of the peptide. The flexible L2 loops of 1510-N
      cover the peptide, and are involved in the protease activity.

PMID- 24121344
TI  - Improvements toward highly accurate diffraction experiments at the macromolecular
      micro-crystallography beamline BL-17A.
AB  - BL-17A is a macromolecular crystallography beamline dedicated to diffraction
      experiments conducted using micro-crystals and structure determination studies
      using a lower energy X-ray beam. In these experiments, highly accurate
      diffraction intensity measurements are definitively important. Since this
      beamline was constructed, the beamline apparatus has been improved in several
      ways to enable the collection of accurate diffraction data. The stability of the
      beam intensities at the sample position was recently improved by modifying the
      monochromator. The diffractometer has also been improved. A new detector table
      was installed to prevent distortions in the diffractometer's base during the
      repositioning of the diffractometer detector. A new pinhole system and an on-axis
      viewing system were installed to improve the X-ray beam profile at the sample
      position and the centering of tiny crystal samples.

PMID- 24121346
TI  - Development of an online UV-visible microspectrophotometer for a macromolecular
      crystallography beamline.
AB  - Measurement of the UV-visible absorption spectrum is a convenient technique for
      detecting chemical changes of proteins, and it is therefore useful to combine
      spectroscopy and diffraction studies. An online microspectrophotometer for the UV
      visible region was developed and installed on the macromolecular crystallography
      beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a
      difference dispersive double monochromator, a mercury-xenon lamp as the light
      source, and a photomultiplier as the detector. The optical path is mostly
      constructed using mirrors, in order to obtain high brightness in the UV region,
      and the confocal optics are assembled using a cross-slit diaphragm like an iris
      to eliminate stray light. This system can measure optical densities up to a
      maximum of 4.0. To study the effect of radiation damage, preliminary measurements
      of glucose isomerase and thaumatin crystals were conducted in the UV region.
      Spectral changes dependent on X-ray dose were observed at around 280 nm,
      suggesting that structural changes involving Trp or Tyr residues occurred in the
      protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm
      was also generated after X-ray irradiation, suggesting the cleavage of a
      disulfide bond. Dose-dependent spectral changes were also observed in cryo
      solutions alone, and these changes differed with the composition of the cryo
      solution. These responses in the UV region are informative regarding the state of
      the sample; consequently, this device might be useful for X-ray crystallography.

PMID- 24121345
TI  - Structure basis 1/2SLPI and porcine pancreas trypsin interaction.
AB  - SLPI (secretory leukocyte protease inhibitor) is a 107-residue protease inhibitor
      which inhibits various serine proteases, including elastase, cathepsin G,
      chymotrypsin and trypsin. SLPI is obtained as a multiple inhibitor in lung
      defense and in chronic airway infection. X-ray crystal structures have so far
      reported that they are full-length SLPIs with bovine alpha-chymotrypsin and
      1/2SLPI (recombinant C-terminal domain of SLPI; Arg58-Ala107) with HNE (human
      neutrophil elastase). To understand the role of this multiple inhibitory
      mechanism, the crystal structure of 1/2SLPI with porcine pancreas trypsin was
      solved and the binding modes of two other complexes compared. The Leu residue
      surprisingly interacts with the S1 site of trypsin, as with chymotrypsin and
      elastase. The inhibitory mechanism of 1/2SLPI using the wide primary binding site
      contacts (from P2' to P5) with various serine proteases is discussed. These
      inhibitory mechanisms have been acquired in the evolution of the protection
      system for acute inflammatory diseases.

PMID- 24121347
TI  - Creation and structure determination of an artificial protein with three complete
      sequence repeats.
AB  - Symfoil-4P is a de novo protein exhibiting the threefold symmetrical beta-trefoil
      fold designed based on the human acidic fibroblast growth factor. First three
      asparagine-glycine sequences of Symfoil-4P are replaced with glutamine-glycine
      (Symfoil-QG) or serine-glycine (Symfoil-SG) sequences protecting from
      deamidation, and His-Symfoil-II was prepared by introducing a protease digestion
      site into Symfoil-QG so that Symfoil-II has three complete repeats after removal
      of the N-terminal histidine tag. The Symfoil-QG and SG and His-Symfoil-II
      proteins were expressed in Eschericha coli as soluble protein, and purified by
      nickel affinity chromatography. Symfoil-II was further purified by anion-exchange
      chromatography after removing the HisTag by proteolysis. Both Symfoil-QG and
      Symfoil-II were crystallized in 0.1 M Tris-HCl buffer (pH 7.0) containing 1.8 M
      ammonium sulfate as precipitant at 293 K; several crystal forms were observed for
      Symfoil-QG and II. The maximum diffraction of Symfoil-QG and II crystals were 1.5
      and 1.1 A resolution, respectively. The Symfoil-II without histidine tag
      diffracted better than Symfoil-QG with N-terminal histidine tag. Although the
      crystal packing of Symfoil-II is slightly different from Symfoil-QG and other
      crystals of Symfoil derivatives having the N-terminal histidine tag, the refined
      crystal structure of Symfoil-II showed pseudo-threefold symmetry as expected from
      other Symfoils. Since the removal of the unstructured N-terminal histidine tag
      did not affect the threefold structure of Symfoil, the improvement of diffraction
      quality of Symfoil-II may be caused by molecular characteristics of Symfoil-II
      such as molecular stability.

PMID- 24121348
TI  - Fundamental studies for the proton polarization technique in neutron protein
      crystallography.
AB  - The isotope effect in conventional neutron protein crystallography (NPC) can be
      eliminated by the proton polarization technique (ppt). Furthermore, the ppt can
      improve detection sensitivity of hydrogen (relative neutron scattering length of
      hydrogen) by approximately eight times in comparison with conventional NPC.
      Several technical difficulties, however, should be overcome in order to perform
      the ppt. In this paper, two fundamental studies to realise ppt are presented:
      preliminary trials using high-pressure flash freezing has shown the advantage of
      making bulk water amorphous without destroying the single crystal; and X-ray
      diffraction and liquid-chromatography/mass-spectrometry analyses of standard
      proteins after introducing radical molecules into protein crystals have shown
      that radical molecules could be distributed non-specifically around proteins,
      which is essential for better proton polarization. 

PMID- 24121349
TI  - High-resolution crystal structure of Streptococcus pyogenes beta-NAD+
      glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly
      water-rich interface.
AB  - One of the virulence factors produced by Streptococcus pyogenes is beta-NAD(+)
      glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected
      host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to
      bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an
      endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a
      complex with SPN. This intracellular complex must be dissociated during export
      through the cell envelope. To provide a structural basis for understanding the
      interactions between SPN and IFS, the complex was overexpressed between the
      mature SPN (residues 38-451) and the full-length IFS (residues 1-161), but it
      could not be crystallized. Therefore, limited proteolysis was used to isolate a
      crystallizable SPNct-IFS complex, which consists of the SPN C-terminal domain
      (SPNct; residues 193-451) and the full-length IFS. Its crystal structure has been
      determined by single anomalous diffraction and the model refined at 1.70 A
      resolution. Interestingly, our high-resolution structure of the complex reveals
      that the interface between SPNct and IFS is highly rich in water molecules and
      many of the interactions are water-mediated. The wet interface may facilitate the
      dissociation of the complex for translocation across the cell envelope.

PMID- 24121350
TI  - JAXA protein crystallization in space: ongoing improvements for growing high
      quality crystals.
AB  - The Japan Aerospace Exploration Agency (JAXA) started a high-quality protein
      crystal growth project, now called JAXA PCG, on the International Space Station
      (ISS) in 2002. Using the counter-diffusion technique, 14 sessions of experiments
      have been performed as of 2012 with 580 proteins crystallized in total. Over the
      course of these experiments, a user-friendly interface framework for high
      accessibility has been constructed and crystallization techniques improved;
      devices to maximize the use of the microgravity environment have been designed,
      resulting in some high-resolution crystal growth. If crystallization conditions
      were carefully fixed in ground-based experiments, high-quality protein crystals
      grew in microgravity in many experiments on the ISS, especially when a highly
      homogeneous protein sample and a viscous crystallization solution were employed.
      In this article, the current status of JAXA PCG is discussed, and a rational
      approach to high-quality protein crystal growth in microgravity based on
      numerical analyses is explained. 

PMID- 24121351
TI  - Crystal structure of human CK2alpha at 1.06 A resolution.
AB  - The Ser/Thr kinase CK2 consists of two catalytic subunits (CK2alpha) and a dimer
      of the regulatory subunits (CK2beta), and is a ubiquitous enzyme that regulates
      growth, proliferation and the survival of cells. CK2 is a remarkable drug target
      for potentially treating a wide variety of tumours and glomerulonephritis. The
      purified CK2alpha protein was crystallized using ethylene glycol as a
      precipitant. The crystal structure of CK2alpha with 21 loci of alternative
      conformations, including a niacin, 19 ethylene glycols and 346 waters, was
      determined at 1.06 A resolution to an Rwork of 14.0% (Rfree = 16.5%). The
      alternative ensemble in the internal hydrophobic core underpins the plasticity of
      the alphaD-helix responsible for the regulation of ATP/GTP binding. The clear
      density map indicates that a niacin molecule, contained in the Escherichia coli
      culture medium, binds to the ATP binding site. An ethylene glycol molecule binds
      in the hydrophobic pocket lateral to the alphaD-helix forming the rim of the
      active site. The other ethylene glycol molecules occupy physiologically
      significant sites, including the CK2beta binding interface and substrate binding
      site, as well as the gap in the crystal packing. Together with water molecules in
      the active site, these structural insights should facilitate drug discovery.

PMID- 24121352
TI  - Real-time investigation of protein unfolding at an air-water interface at the 1 s
      time scale.
AB  - Protein unfolding at an air-water interface has been demonstrated such that the X
      ray reflectivity can be measured with an acquisition time of 1 s using a recently
      developed simultaneous multiple-angle-wavelength-dispersive X-ray reflectometer.
      This has enabled the electron density profile of the adsorbed protein molecules
      to be obtained in real time. A globular protein, lysozyme, adsorbed at the air
      water interface is found to unfold into a flat shape within 1 s.

PMID- 24121353
TI  - Crystal structure of the N-terminal domain of MinC dimerized via domain swapping.
AB  - Proper cell division at the mid-site of gram-negative bacteria reflects critical
      regulation by the min system (MinC, MinD and MinE) of the cytokinetic Z ring,
      which is a polymer composed of FtsZ subunits. MinC and MinD act together to
      inhibit aberrantly positioned Z-ring formation. MinC consists of two domains: an
      N-terminal domain (MinCNTD), which interacts with FtsZ and inhibits FtsZ
      polymerization, and a C-terminal domain (MinCCTD), which interacts with MinD and
      inhibits the bundling of FtsZ filaments. These two domains reportedly function
      together, and both are essential for normal cell division. The full-length
      dimeric structure of MinC from Thermotoga maritima has been reported, and shows
      that MinC dimerization occurs via MinCCTD; MinCNTD is not involved in
      dimerization. Here the crystal structure of Escherichia coli MinCNTD (EcoMinCNTD)
      is reported. EcoMinCNTD forms a dimer via domain swapping between the first beta
      strands in each subunit. It is therefore suggested that the dimerization of full
      length EcoMinC occurs via both MinCCTD and MinCNTD, and that the dimerized
      EcoMinCNTD likely plays an important role in inhibiting aberrant Z-ring
      localization.

PMID- 24121354
TI  - High-resolution X-ray crystal structure of bovine H-protein using the high
      pressure cryocooling method.
AB  - Recently, many technical improvements in macromolecular X-ray crystallography
      have increased the number of structures deposited in the Protein Data Bank and
      improved the resolution limit of protein structures. Almost all high-resolution
      structures have been determined using a synchrotron radiation source in
      conjunction with cryocooling techniques, which are required in order to minimize
      radiation damage. However, optimization of cryoprotectant conditions is a time
      consuming and difficult step. To overcome this problem, the high-pressure
      cryocooling method was developed (Kim et al., 2005) and successfully applied to
      many protein-structure analyses. In this report, using the high-pressure
      cryocooling method, the X-ray crystal structure of bovine H-protein was
      determined at 0.86 A resolution. Structural comparisons between high- and ambient
      pressure cryocooled crystals at ultra-high resolution illustrate the versatility
      of this technique. This is the first ultra-high-resolution X-ray structure
      obtained using the high-pressure cryocooling method.

PMID- 24121355
TI  - Evaluation of performance for IBARAKI biological crystal diffractometer iBIX with
      new detectors.
AB  - The IBARAKI biological crystal diffractometer, iBIX, is a high-performance time
      of-flight neutron single-crystal diffractometer for elucidating mainly the
      hydrogen, protonation and hydration structures of biological macromolecules in
      various life processes. Since the end of 2008, iBIX has been available to users'
      experiments supported by Ibaraki University. Since August 2012, an upgrade of the
      14 existing detectors has begun and 16 new detectors have been installed for
      iBIX. The total measurement efficiency of the present diffractometer has been
      improved by one order of magnitude from the previous one with the increasing of
      accelerator power. In December 2012, commissioning of the new detectors was
      successful, and collection of the diffraction dataset of ribonucrease A as a
      standard protein was attempted in order to estimate the performance of the
      upgraded iBIX in comparison with previous results. The resolution of diffraction
      data, equivalence among intensities of symmetry-related reflections and
      reliability of the refined structure have been improved dramatically. iBIX is
      expected to be one of the highest-performance neutron single-crystal
      diffractometers for biological macromolecules in the world.

PMID- 24121356
TI  - A convenient tool for gas derivatization using fine-needle capillary mounting for
      protein crystals.
AB  - Gas derivatization of protein crystals is useful not only to analyse gas-binding
      proteins but also to solve the phase problem of X-ray crystallography by using
      noble gases. However, the gas pressurization tools for these experiments are
      often elaborate and need to release the gas before flash-cooling. To simplify
      this step, a procedure using a fine-needle capillary to mount and flash-cool
      protein crystals under the pressurization of gases has been developed. After the
      crystals are picked up with the capillary, the capillary is sealed with an
      adhesive and then connected directly to a gas regulator. The quality of the
      diffraction data using this method is comparable with that of data from
      conventional pressurization procedures. The preparation of xenon-derivatives of
      hen egg-white lysozyme using this method was a success. In the derivatives, two
      new xenon binding sites were found and one of their sites vanished by releasing
      the gas. This observation shows the availability of flash-cooling under gas
      pressurization. This procedure is simple and useful for preparing gas-derivative
      crystals. 

PMID- 24121357
TI  - Numerical model of protein crystal growth in a diffusive field such as the
      microgravity environment.
AB  - It is said that the microgravity environment positively affects the quality of
      protein crystal growth. The formation of a protein depletion zone and an impurity
      depletion zone due to the suppression of convection flow were thought to be the
      major reasons. In microgravity, the incorporation of molecules into a crystal
      largely depends on diffusive transport, so the incorporated molecules will be
      allocated in an orderly manner and the impurity uptake will be suppressed,
      resulting in highly ordered crystals. Previously, these effects were numerically
      studied in a steady state using a simplified model and it was determined that the
      combination of the diffusion coefficient of the protein molecule (D) and the
      kinetic constant for the protein molecule (beta) could be used as an index of the
      extent of these depletion zones. In this report, numerical analysis of these
      depletion zones around a growing crystal in a non-steady (i.e. transient) state
      is introduced, suggesting that this model may be used for the quantitative
      analysis of these depletion zones in the microgravity environment. 

PMID- 24121359
TI  - Dispersion corrections in graphenic systems: a simple and effective model of
      binding.
AB  - We combine high-level theoretical and ab initio understanding of graphite to
      develop a simple, parametrized force-field model of interlayer binding in
      graphite, including the difficult non-pairwise-additive coupled-fluctuation
      dispersion interactions. The model is given as a simple additive correction to
      standard density functional theory (DFT) calculations, of form DeltaU(D) =
      f(D)[U(vdW)(D) - U(DFT)(D)] where D is the interlayer distance. The functions are
      parametrized by matching contact properties, and long-range dispersion to known
      values, and the model is found to accurately match high-level ab initio results
      for graphite across a wide range of D values. We employ the correction on the
      bigraphene binding and graphite exfoliation problems, as well as lithium
      intercalated graphite LiC6. We predict the binding energy of bigraphene to be
      0.27 J m(-2), and the exfoliation energy of graphite to be 0.31 J m(-2),
      respectively slightly less and slightly more than the bulk layer binding energy
      0.295 J m(-2)/layer. Material properties of LiC6 are found to be essentially
      unchanged compared to the local density approximation. This is appropriate in
      view of the relative unimportance of dispersion interactions for LiC6 layer
      binding.

PMID- 24121360
TI  - pH switchable and fluorescent ratiometric squarylium indocyanine dyes as
      extremely alkaline solution sensors.
AB  - pH indicators based on optical analysis play an important role in monitoring pH
      changes. Squarylium indocyanine (SICy) dyes have been developed to be used as
      extremely alkaline solution sensors. The absorbance and fluorescence intensities
      of the SICy dyes were quenched at a pH value of 13, and then recovered by adding
      acid to adjust the pH to 7. This reversible switching process could be repeated
      several times without significant loss of fluorescence. NMR and mass spectrometry
      analyses demonstrate nucleophilic addition of hydroxide ions to the N
      heterocycle. This study opens a new avenue to the design of fluorescent
      ratiometrics in extremely alkaline systems. 

PMID- 24121361
TI  - A family with factor-XI deficiency due to a compound heterozygosis between Gln 47
      Pro (new mutation) in exon 3 and Leu 619 Pro in exon 15.
AB  - A new factor XI mutation (Gln 47 Pro) has been found in combination with another
      known mutation (Leu 619 Pro) in a female patient with FXI deficiency and a
      moderate bleeding tendency. FXI activity and antigen in the proposita were 2%
      activity and less than 5% of normal, respectively. The parents are not
      consanguineous and are asymptomatic. The father is heterozygote for the new
      mutation whereas the mother is heterozygote for the known mutation. Other family
      members are heterozygotes for either one of the two mutations. The new mutation
      is not a polymorphism as it was not found in the population of the area. The
      geographical area, north-east of Italy, of the present family is the same area
      where a cluster of another new mutation (Ile 436 Lys) was recently reported. No
      relation was found between the present family and those with the previous
      mutation. 

PMID- 24121363
TI  - Trauma Whipple: do or don't after severe pancreaticoduodenal injuries? An
      analysis of the National Trauma Data Bank (NTDB).
AB  - BACKGROUND: Pancreaticoduodenectomy for trauma (PDT) is a rare procedure,
      reserved for severe pancreaticoduodenal injuries. Using the National Trauma Data
      Bank (NTDB), our aim was to compare outcomes of PDT patients to similarly injured
      patients who did not undergo a PDT. METHODS: Patients with pancreatic or duodenal
      injuries treated with PDT (ICD-9-CM 52.7) were identified in the NTDB 2008-2010
      Research Data Sets. We excluded those who underwent delayed PDT (>4 days). The
      PDT group (n = 39) was compared to patients with severe combined
      pancreaticoduodenal injuries (grade 4 or 5) who did not undergo PDT (non-PDT
      group, n = 38). Patients who died in the emergency department or did not undergo
      a laparotomy were excluded. Our primary outcome was death. Secondary outcomes
      were intensive care unit length of stay (LOS), hospital LOS, and total ventilator
      days. A multivariate model was used to determine predictors of in-hospital
      mortality within each group and in the overall cohort. RESULTS: The non-PDT group
      had a significantly lower systolic blood pressure and Glasgow Coma Scale values
      at baseline and more severe duodenal, pancreatic, and liver injuries. There were
      no significant differences in outcomes between the two groups. The Injury
      Severity Score was the only independent predictor of mortality among PDT patients
      [odds ratio (OR) 1.12, 95 % confidence interval (CI) 1.01-1.24] and in the entire
      cohort (OR 1.06, 95 % CI 1.01-1.12). The operative technique did not influence
      any of the outcomes. CONCLUSIONS: Compared to non-PDT, PDT did not result in
      improved outcomes despite a lower physiologic burden among PDT patients. More
      conservative procedures for high-grade injuries of the pancreaticoduodenal
      complex may be appropriate.

PMID- 24121362
TI  - Value of scintigraphy for assessing delayed gastric emptying after pancreatic
      surgery.
AB  - BACKGROUND: Delayed gastric emptying (DGE) occurs frequently after pancreatic
      surgery. Recently a consensus definition of DGE was introduced, and this grading
      system is currently widely used. The aim of this study was to compare results of
      gastric emptying scintigraphy with the grade of DGE after pancreatic surgery.
      METHODS: In 44 patients undergoing exploration for a pancreatic head or
      periampullary tumor, 28 pancreatoduodenectomies (PDs) and 16 double-bypass
      procedures were performed. All patients underwent preoperative and postoperative
      gastric emptying scintigraphy. We investigated whether the incidence of DGE was
      correlated with the results of gastric emptying scintigraphy. RESULTS: DGE
      occurred in 19 (43 %) patients. Clinically relevant DGE (grades B and C)
      prevailed in the PD group. Median postoperative residual activity at t = 2 h
      (%RA120) in these groups was 36 % (no DGE), 75 % (grade A), 93 % (grade B), and
      95 % (grade C). DGE grade B or C was found in 7 of 10 patients with %RA120 of
      >=94 % on postoperative day (POD) 7. CONCLUSIONS: Postoperative %RA120 on
      scintigraphy is positively associated with severity of DGE. Gastric emptying
      scintigraphy on POD 7 can predict the severity of DGE. When postoperative gastric
      emptying scintigraphy shows high residual radioactivity, the likelihood of
      further progression to grade B or C DGE is high and warrants investigation for
      underlying causes.

PMID- 24121364
TI  - Impact of the reconstruction method on delayed gastric emptying after pylorus
      preserving pancreaticoduodenectomy: a prospective randomized study.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is of considerable concern in patients
      undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prolonged hospital
      stay, increased cost, and decreased quality of life add on to interventions
      needed to treat DGE. This study was conducted to determine if performing
      duodenojejunostomy via the antecolic rather than the retrocolic route improved
      incidence of DGE. METHODS: Patients undergoing PPPD between April 2007 and
      November 2009 were randomized for either antecolic or retrocolic reconstruction
      of the duodenojejunostomy. DGE was then assessed by clinical criteria on
      postoperative day (POD) 10. A paracetamol absorption test was also administered
      with a liquid meal, and serial plasma levels of intestinal peptides were
      measured. RESULTS: Overall, 64 patients were amenable for analysis: 36 in the
      antecolic group and 28 in the retrocolic group. The incidences of DGE on POD 10
      were 17.6 and 23.1 % (antecolic vs. retrocolic, respectively) (p = 0.628). The
      two groups did not differ in regard to their median (interquartile range)
      postoperative hospital length of stay [13.0 (10.0-17.5) vs. 12.5 (11.0-17.0)
      days; p = 0.446], time to regular diet [5 (5-7) vs. 5 (4-6) days; p = 0.353], or
      morbidity (52.9 vs. 50.0 %; p = 0.777). The median length of nasogastric tube
      decompression was similar in the two groups [4 (3-7) vs. 3 (3-5) days; p =
      0.600]. Levels of paracetamol and glucagon-like peptide-1 were markedly decreased
      in patients with DGE. CONCLUSIONS: Antecolic reconstruction after PPPD does not
      improve the occurrence/the incidence of DGE and is similar to retrocolic
      reconstruction with regard to secondary outcome parameters.

PMID- 24121365
TI  - Preparing for prospective clinical trials: a national initiative of an excellence
      registry for consecutive pancreatic cancer resections.
AB  - BACKGROUND: Despite significant improvements in perioperative mortality as well
      as response rates to multimodality treatment, results after surgical resection of
      pancreatic adenocarcinoma with respect to long-term outcomes remain
      disappointing. Patient recruitment for prospective international trials on
      adjuvant and neoadjuvant regimens is challenging for various reasons. We set out
      to assess the preconditions and potential to perform perioperative trials for
      pancreatic cancer within a well-established Austrian nationwide network of
      surgical and medical oncologists (Austrian Breast & Colorectal Cancer Study
      Group). METHODS: From 2005 to 2010 five high-volume centers and one medium-volume
      center completed standardized data entry forms with 33 parameters (history and
      patient related data, preoperative clinical staging and work-up, surgical details
      and intraoperative findings, postoperative complications, reinterventions,
      reoperations, 30-day mortality, histology, and timing of multimodality
      treatment). Outside of the study group, in Austria pancreatic resections are
      performed in three "high-volume" centers (>10 pancreatic resections per year),
      three "medium-volume" centers (5-10 pancreatic resections per year), and the rest
      in various low-volume centers (<5 pancreatic resections per year) in Austria.
      Nationwide data for prevalence of and surgical resections for pancreatic
      adenocarcinoma were contributed by the National Cancer Registry of Statistics of
      Austria and the Austrian Health Institute. RESULTS: In total, 492 consecutive
      patients underwent pancreatic resection for ductal adenocarcinoma. All
      postoperative complications leading to hospital readmission were treated at the
      primary surgical department and documented in the database. Overall morbidity and
      pancreatic fistula rate were 45.5 % and 10.1 %, respectively. Within the entire
      cohort there were 9.8 % radiological reinterventions and 10.4 % reoperations.
      Length of stay was 16 days in median (0-209); 12 of 492 patients died within 30
      days after operation, resulting in a 30-day mortality rate of 2.4 %. Seven of the
      total 19 deaths (36.8 %) occurred after 30 days, during hospitalization at the
      surgical department, resulting in a hospital mortality rate of 3.9 % (19/492).
      With a standardized histopathological protocol, there were 70 % (21/30) R0
      resections, 30 % (9/30) R1 resections, and no R2 resections in Vienna and 62.7 %
      (32/51) R0 resections, 35.3 % (18/51) R1 resections, and 2 % (1/51) R2 resections
      in Salzburg. Resection margin status with nonstandardized protocols was
      classified as R0 in 82 % (339/411), R1 in 16 % (16/411), and R2 in 1.2 % (5/411).
      Perioperative chemotherapy was administered in 81.1 % of patients (8.3 %
      neoadjuvant; 68.5 % adjuvant; 4.3 % palliative); chemoradiotherapy (1.6 %
      neoadjuvant; 3 % adjuvant; 0.2 % palliative), in 4.9 % of patients. The six
      centers that contributed to this registry initiative provided surgical treatment
      to 40 % of all Austrian patients, resulting in a median annual recruitment of 85
      (51-104) patients for the entire ABCSG-group and a median of 11.8 (0-38)
      surgeries for each individual department. CONCLUSIONS: Surgical quality data of
      the ABCSG core pancreatic group are in line with international standards. With
      continuing centralization the essential potential to perform prospective clinical
      trials for pancreatic adenocarcinoma is given in Austria. Several protocol
      proposals aiming at surgical and multimodality research questions are currently
      being discussed

PMID- 24121366
TI  - Manual isolation of adipose-derived stem cells from human lipoaspirates.
AB  - In 2001, researchers at the University of California, Los Angeles, described the
      isolation of a new population of adult stem cells from liposuctioned adipose
      tissue that they initially termed Processed Lipoaspirate Cells or PLA cells.
      Since then, these stem cells have been renamed as Adipose-derived Stem Cells or
      ASCs and have gone on to become one of the most popular adult stem cells
      populations in the fields of stem cell research and regenerative medicine.
      Thousands of articles now describe the use of ASCs in a variety of regenerative
      animal models, including bone regeneration, peripheral nerve repair and
      cardiovascular engineering. Recent articles have begun to describe the myriad of
      uses for ASCs in the clinic. The protocol shown in this article outlines the
      basic procedure for manually and enzymatically isolating ASCs from large amounts
      of lipoaspirates obtained from cosmetic procedures. This protocol can easily be
      scaled up or down to accommodate the volume of lipoaspirate and can be adapted to
      isolate ASCs from fat tissue obtained through abdominoplasties and other similar
      procedures. 

PMID- 24121367
TI  - A solid state fungal fermentation-based strategy for the hydrolysis of wheat
      straw.
AB  - This paper reports a solid-state fungal fermentation-based pre-treatment strategy
      to convert wheat straw into a fermentable hydrolysate. Aspergillus niger was
      firstly cultured on wheat straw for production of cellulolytic enzymes and then
      the wheat straw was hydrolyzed by the enzyme solution into a fermentable
      hydrolysate. The optimum moisture content and three wheat straw modification
      methods were explored to improve cellulase production. At a moisture content of
      89.5%, 10.2 +/- 0.13 U/g cellulase activity was obtained using dilute acid
      modified wheat straw. The addition of yeast extract (0.5% w/v) and minerals
      significantly improved the cellulase production, to 24.0 +/- 1.76 U/g. The
      hydrolysis of the fermented wheat straw using the fungal culture filtrate or
      commercial cellulase Ctec2 was performed, resulting in 4.34 and 3.13 g/L glucose
      respectively. It indicated that the fungal filtrate harvested from the fungal
      fermentation of wheat straw contained a more suitable enzyme mixture than the
      commercial cellulase.

PMID- 24121368
TI  - Characterization of the biofuel potential of a newly isolated strain of the
      microalga Botryococcus braunii Kutzing from Assam, India.
AB  - Botryococcus braunii GUBIOTJTBB1 was isolated from a freshwater reservoir in
      Assam, India and its taxonomic identity was confirmed by 18S rRNA sequence
      analysis. Biofuel potential of the microalga strain was assessed from batch
      culture under laboratory conditions, based on its lipid content and energy value
      of the dried biomass. Total lipid of 57.14% and hexane extractable crude
      hydrocarbon of 52.6% were recorded maximum at 56 and 28 days respectively, which
      vary upon culture durations. The energy value (54.69 kJ/g) of the strain's
      sundried biomass was found higher than that of petroleum diesel fuel and nearly
      twice than other microalgae strains compared. The strain GUBIOTJTBB1 was found
      superior in terms of total lipid and hydrocarbon contents comparing to the
      previously reported Indian strains of B. braunii. With further improvements in
      growth, the strain could become an ideal feedstock for potential biofuel
      production in the prevailing climatic conditions of the region.

PMID- 24121369
TI  - Simultaneous removal of phosphorus and nitrogen from sewage using a novel combo
      system of fluidized bed reactor-membrane bioreactor (FBR-MBR).
AB  - A FBR-MBR combo system was designed as a novel approach for simultaneous
      phosphorus and nitrogen removal from sewage. The combo system was evaluated more
      than 7 months under variable pH (7.5-9.5), hydraulic retention times (HRT=2-10h),
      intermittent aeration cycles (IAC) (on/off=60/60-15/45 min) and sludge retention
      times (SRT=10-60 d). Prior recovery of phosphorus as struvite in the FBR enhanced
      nitrogen and COD removal efficiency in MBR. Under optimum operating conditions
      (pH=9, HRT=6h and IAC=45/15 min), PO4(3-)-P, NH4(+)-N and COD removal
      efficiencies were 92.6 +/- 4.2, 98.7 +/- 1.2 and 99.3 +/- 0.5%, respectively.
      Stable mixed liquor suspended solid concentration (3.0-5.0 g/L); enhanced
      nitrification-denitrification activity (78-92%) and reduced transmembrane
      pressure were also achieved. Compared to soluble microbial products,
      extracellular polymeric substances (EPS) showed strong correlation with fast
      membrane fouling. Among EPS components, carbohydrate rather than protein was
      associated with membrane fouling. Except HRT, all parameters considered (pH, IAC,
      SRT) showed a significant effect on removal efficiency.

PMID- 24121370
TI  - Simultaneously concentrating and pretreating of microalgae Chlorella spp. by
      three-phase partitioning.
AB  - In this study, a recent simple separation technique, three-phase partitioning
      (TPP), was used for concentrating microalgae Chlorella spp. for the first time.
      More than 91.7% of the biomass precipitated in the interlayer of the system in 10
      min. Temperature, initial concentration and ratio of ethanol to dipotassium
      hydrogen phosphate (DKP) were observed to negatively correlate with concentration
      factor while pH showed no significant influences. Using this method, biomass
      could be concentrated with much lower energy consumption and concentrated biomass
      could be conveniently collected. Besides, together with concentrating, TPP
      concentrated microalgae cells showed 26.3% increase in lipid extraction yield.
      Additionally, similarities in fatty acid profile indicated the avoidance of
      influence on lipid quality from chemicals. This study demonstrated the
      feasibility of TPP for microalgae biodiesel production.

PMID- 24121371
TI  - Anaerobic membrane bioreactor (AnMBR) for bamboo industry wastewater treatment.
AB  - Bamboo industry wastewater (BIWW) poses severe environmental problems because of
      its high organic matter content. In this study, anaerobic membrane bioreactor
      (AnMBR) was applied for BIWW treatment. During the start-up stage, the system
      presented an effective degradation with a final COD removal of 91%. Compared to
      the intermittent mode, a higher membrane rejection (45% COD, 60% NH3-N) was
      obtained when the system was operated continuously. N2 flushing was applied for
      membrane cleaning, and the cleaning efficiency was significantly influenced by
      the hydraulic retention time (HRT). While operated under HRT >= 5 d, membrane
      fouling could be effectively controlled. Scanning electron microscopy-energy
      dispersive X-ray (SEM-EDX) analysis indicated the membrane top area suffered the
      most serious fouling. Gel permeation chromatography (GPC) and gas chromatography
      mass spectrometry (GC-MS) analyses revealed most organic matter in BIWW was
      eliminated by AnMBR. However, benzene and fluoro derivatives were detected in the
      permeate as the by-products.

PMID- 24121372
TI  - Polyhydroxybutyrate production by direct use of waste activated sludge in
      phosphorus-limited fed-batch culture.
AB  - Polyhydroxybutyrate (PHB) production directly by waste activated sludge (WAS) was
      investigated in aerobic fed-batch conditions using acetic acid as substrate. PHB
      production was induced by phosphorus limitation. WAS of different origin were
      tested with various degrees of phosphorus limitation and PHB contents of up to
      70% (gCOD PHB/gCOD particulate) were obtained. This strategy showed the
      importance of maintaining cell growth for PHB production in order to increase PHB
      concentration and that the degree of phosphorus limitation has a direct impact on
      the quantity of PHB produced. Pyrosequencing of 16S rRNA transcripts showed
      changes in the active bacteria of the WAS microbial community as well as the
      acclimation of populations depending on sludge origin. The monitoring of the
      process appeared as the key factor for optimal PHB production by WAS. Different
      strategies are discussed and compared in terms of carbon yield and PHB content
      with the feast and famine selection process.

PMID- 24121373
TI  - Performance of the ANAMMOX process using multi- and single-fed upflow anaerobic
      sludge blanket reactors.
AB  - The performance of the ANAMMOX process was investigated in two identical
      laboratory-scale multi- and single-fed upflow anaerobic sludge blanket (UASB)
      reactors (denoted R1 and R0) at different hydraulic residence times (HRTs)
      varying from 2.06 to 1.52 h and NH4(+)-N inf concentrations ranging from 70 to
      266 mg L(-1). The substrate removal efficiencies of both reactors decreased as
      HRT decreased and NH4(+)-N inf increased. The kinetics of these reactions were
      analyzed, and the Stover-Kincannon model was appropriate to describe the process
      kinetics of the reactors. In addition, an empirical model incorporating the
      influent substrate concentration and HRT adequately described R1. Shock
      experiments were conducted in which the reactors were subjected to transient
      shock loads. The results showed that the operation of R1 was more stable than
      that of R0, especially in response to the substrate shocks. Subsequently, the
      properties of the ANAMMOX granules and the effects of the feeding protocol on
      those properties were investigated.

PMID- 24121374
TI  - Lessons derived from studies in the elderly: the role of nutrition education in
      cardiovascular disease prevention.

PMID- 24121375
TI  - PET and PET/CT imaging in thyroid and adrenal diseases: an update.
AB  - Positron emission tomography (PET) and PET/computed tomography (PET/CT) with
      different tracers are imaging methods increasingly used in patients with thyroid
      and adrenal diseases. The aim of this article is to provide an overview based on
      literature data about the usefulness of PET imaging in this setting. PET and
      PET/CT with different tracers have been used in patients with thyroid diseases
      including differentiated thyroid carcinoma, medullary thyroid carcinoma, and
      poorly differentiated and anaplastic thyroid carcinoma. The usefulness of 18F-FDG
      PET and PET/CT in assessing indeterminate thyroid nodules at fine needle
      aspiration biopsy and the clinical relevance of thyroid incidental 18F-FDG uptake
      has also been evaluated. Currently, great interest is being shown in a variety of
      PET tracers that target specific characteristics of adrenal gland function,
      allowing a more accurate characterization of adrenal masses and staging of
      adrenal tumors. Since PET/CT using different tracers is an expensive diagnostic
      tool which necessitates ionizing radiation exposure, cost-effectiveness studies
      are needed in order to define the appropriate use of this diagnostic method in
      various endocrine disorders. 

PMID- 24121376
TI  - Premenopause: the endocrinology of reproductive decline.

PMID- 24121377
TI  - The "depressive" face of osteoporosis and the "osteoporotic" face of depression.
AB  - Osteoporosis and depression are two chronic diseases that affect large population
      groups with great impact on morbidity, mortality and quality of life. An
      association between osteoporosis and depression has been described in the
      literature. Definitely, limited data suggest that osteoporosis may enhance
      depressive symptoms, while far more studies have shown that depression adversely
      affects bone density and increases fracture risk. However, neither causation nor
      a firm pathophysiological connection has been established. Thus the correlation
      of these diseases is still under research. This review comments on a plausible
      causative relationship and underlying mechanisms that might elucidate the link
      between two very common diseases. We describe the possible impact of osteoporosis
      on moods and the (better established) effect of depression on bone health. We
      also describe the effect of medication and review hormonal and cellular signals
      that may explain this effect. 

PMID- 24121378
TI  - Metabolic and other effects of pioglitazone as an add-on therapy to metformin in
      the treatment of polycystic ovary syndrome (PCOS).
AB  - Insulin resistance is a key pathogenic defect of the clustered metabolic
      disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin
      sensitizer acting in the liver and the peripheral tissues that ameliorates the
      metabolic and reproductive defects in PCOS. In addition, pioglitazone is an
      insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin
      resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used
      as a combined treatment due to their "add-on effect" on insulin resistance.
      Although the beneficial role of troglitazone (a member of the thiazolidinediones
      (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is
      available in the market. A few small randomized controlled trials have directly
      compared the effectiveness of pioglitazone in women with PCOS, while there are a
      limited number of small studies that support the beneficial metabolic add-on
      effect of pioglitazone on metformin-treated PCOS women as compared to metformin
      or pioglitazone monotherapy. These findings suggest a potentially promising role
      for combined pioglitazone/metformin treatment in the management of PCOS in
      metformin-resistant patients. In view of recent concerns regarding pioglitazone
      usage and its associated health risk, we aim to compare the pros and cons of each
      drug regarding their metabolic and other hormonal effects in women with PCOS and
      to explore the possible beneficial effect of combined therapy in certain cases,
      taking into consideration the teratogenic effect of pioglitazone. Finally, we
      discuss the need for a randomized controlled trial that will evaluate the
      metabolic and other hormonal effects of combined metformin/pioglitazone treatment
      in PCOS with selective treatment targets. 

PMID- 24121379
TI  - A 50-year follow-up of the Seven Countries Study: Prevalence of cardiovascular
      risk factors, food and nutrient intakes among Cretans.
AB  - OBJECTIVE: To identify the cardiovascular disease (CVD) risk-factor status and
      dietary habits of the surviving elderly participants of the initial Seven
      Countries Study (SCS) cohort and newly recruited middle-aged men from the same
      villages. DESIGN: Our total cohort of remaining survivors of the SCS consisted of
      27 men aged 90 years old and over, while a younger cross-sectional study of 85
      men between 53 and 73 years of age of the same catchment area were also examined.
      Biochemical, anthropometric, dietetic and lifestyle CVD risk factors information
      was obtained. RESULTS: It was found that being overweight and having systolic
      blood pressure higher than the recommended were highly prevalent (>75%) among
      both age groups as well as abdominal obesity (about 50%). Hypercholesterolemia
      was highly prevalent in the younger population (68.8%), while smoking rates were
      relatively low among elderly. The daily meat consumption of SCS participants had
      doubled, from 35g in the 1960s to 76g among the SCS survivors in 2010 (p=0.002),
      while daily fruit and vegetable consumption had dropped from 656g to 266g
      (p<0.001). The younger participants also had increased dietary meat (130g/day)
      (p<0.001) and decreased fruits-vegetables intake (412g/day) (p<0.001) compared to
      50 years ago. However, the younger population and elderly subjects showed higher
      fish intake (91g/day and 38g/day respectively, p<0.001) compared to 1960 and
      favorable olive oil consumption. In regard to nutrient intake, the majority of
      the subjects did not meet the recommendations for CVD prevention. CONCLUSIONS:
      The study population is at increased risk for the development of CVD, while
      current dietary habits of the SCS survivors partially differed from those of 50
      years ago.

PMID- 24121380
TI  - Impact of religiosity/spirituality on biological and preclinical markers related
      to cardiovascular disease. Results from the SPILI III study.
AB  - OBJECTIVE: This study aimed at exploring to what extent psychosocial factors,
      such as religiosity/spirituality and sense of coherence, mediate the negative
      effects of stress on a variety of cardiometabolic indicators, i.e., hypertension,
      diabetes, cardiovascular and cerebrovascular disease, and atherosclerotic bio
      clinical markers. DESIGN: A total of 220 subjects (66.2+/-16.0 years) of the
      SPILI III cohort (1988-2012) attending a primary care setting in Spili, a rural
      town in Crete, represented the target group for the present study. Of these, 195
      (88.6%) participated in the re-examination (67.2+/-15.2 years). All participants
      underwent a standardized procedure including evaluation of anthropometric
      measurements, biochemical indicators of atherosclerosis, stress hormones, in
      parallel with ultrasound measurements of carotid intima media thickness (IMT).
      Religiosity, spirituality and sense of coherence were evaluated with the use of
      international questionnaires translated into the Greek language and
      linguistically validated. RESULTS: Participants with higher levels of religious
      and spiritual beliefs presented lower levels of carotid IMT (1.01+/-0.101 vs
      1.53+/-0.502 mm, p<0.001). Patterns of inverse relationships were also observed
      between religiosity/spirituality and prevalence of diabetes (35.1% vs. 2%,
      p<0.001) with an estimated diabetes risk, fully adjusted odds ratio, 95% CI: 0.91
      (0.87-0.94). Highly religious participants presented lower serum cortisol levels
      (12.3+/-5.8 vs. 18.2+/-5.1 MUg/dl, p<0.001). Sense of coherence was positively
      associated with religiosity/spirituality [mean SOC (SD): 123+/-20 vs. 158+/-15)
      p<0.001]. CONCLUSIONS: These findings may be associated with a possible
      favourable effect of religiosity/spirituality on several cardio-metabolic
      determinants, therefore deserving further attention by healthcare practitioners
      and researchers.

PMID- 24121381
TI  - Decreased circulating 25-(OH) Vitamin D concentrations in obese female children
      and adolescents: positive associations with Retinol Binding Protein-4 and
      Neutrophil Gelatinase-associated Lipocalin.
AB  - OBJECTIVE: Hypovitaminosis D has been associated with adult as well as childhood
      obesity. Retinol-binding-protein-4 (RBP-4) and Neutrophil Gelatinase-associated
      Lipocalin (NGAL) are altered in obese individuals. The aim of this study was to
      examine circulating 25-(OH) Vitamin D (25-(OH) D) concentrations according to BMI
      and its associations with RBP-4 and NGAL in female children and adolescents.
      DESIGN: Seventy-nine (79) children, aged 8-16 years, were studied and divided
      into four groups: 19 control (BMI z-score range -2.15 - 1.24), 20 overweight
      (1.34 - 2.49), 20 obese (2.50 - 2.87) and 20 ultra-obese (3 - 4.37). Patients
      were derived from a Pediatric Obesity Clinic. Plasma 25-(OH) D, RBP-4 and NGAL
      concentrations were measured with specific assays. RESULTS: Plasma 25-(OH) D
      concentrations were decreased significantly in the ultra-obese (p=0.005) and
      marginally in the obese group (p=0.05) compared to the control group. In the
      entire BMI range, Spearman correlations revealed strong positive associations
      between 25-(OH) D and RBP-4 (r=0.349, p=0.002) and between 25-(OH) D and NGAL
      (r=0.338, p=0.003). CONCLUSIONS: 25-(OH) D is deficient in a clinical population
      of obese female children and adolescents, whereas in the entire BMI range 25-(OH)
      D is associated with RBP4 and NGAL concentrations. Longitudinal studies are
      needed to reveal the role of these associations in metabolic alterations related
      to childhood and adolescent obesity and associated metabolic morbidities.

PMID- 24121382
TI  - Sex steroids and sex hormone-binding globulin in postmenopausal women with
      nonalcoholic fatty liver disease.
AB  - OBJECTIVE: The evaluation of serum sex steroids and sex hormone-binding globulin
      (SHBG) levels in postmenopausal women with nonalcoholic fatty liver disease
      (NAFLD) and their association to the disease severity. DESIGN: Twenty-two
      postmenopausal women with biopsy-proven NAFLD and 18 matched controls were
      recruited. Blood samples for serum SHBG, total testosterone, estradiol levels and
      standard biochemical tests were obtained after overnight fasting. Free androgen
      index (FAI), calculated free (cFT) and bioavailable testosterone were estimated
      by standard formulas. RESULTS: The NAFLD group had lower serum SHBG levels and
      higher values of cFT, bioavailable testosterone and FAI, despite exhibiting
      similar to controls levels of serum total testosterone and estradiol. Serum SHBG
      levels (adjusted odds ratio [aOR]=0.912; 95% CI 0.854-0.973), bioavailable
      testosterone (aOR=1.254; 95% CI 1.010-1.556) and FAI (aOR=2.567; 95% CI 1.153
      5.716), but not cFT, were associated with NAFLD independently of age, body mass
      index (BMI) and waist circumference. Serum estradiol levels were associated with
      the presence of nonalcoholic steatohepatitis (NASH) independently of age, BMI and
      waist circumference (aOR=0.727; 95% CI 0.537-0.985). CONCLUSIONS: Low SHBG levels
      and high metabolically active testosterone fractions were independently
      associated with NAFLD. Among NAFLD patients, serum estradiol levels were
      independently associated with NASH. However, these results need further
      validation from large-scale studies.

PMID- 24121383
TI  - Clinical utility of FDG-PET for diagnosis of adrenal mass: a large single-center
      experience.
AB  - OBJECTIVE: To examine the clinical utility of 18F-fluorodeoxyglucose-positron
      emission tomography (FDG-PET) for diagnosing whether an adrenal mass is
      malignant, in contemporary clinical practice. DESIGN: Retrospective medical
      record review of patients from 2 databases at a large hospital. The first
      database consisted of patients who underwent FDG-PET between the years 2009 to
      2011 while the second database included patients who had histological diagnosis
      of adrenal mass between the years 1997 to 2011. RESULTS: 3.4% of 2921 patients
      had adrenal FDG uptake. Approximately 43% of them did not exhibit corresponding
      adrenal mass. FDG-PET performance parameters were better if a cutoff of SUV
      (standardized uptake value) >=3 was used to define positivity. The imaging
      characteristics of malignant adrenal masses and pheochromocytoma were similar but
      differed remarkably compared to those of benign tumors. Serial imaging revealed
      that the malignant adrenal masses consistently exhibited high CT attenuation,
      while more than half of them initially exhibited SUV<3 and in some cases FDG
      uptake indistinguishable from the background. The FDG-PET results were
      confirmatory in 87% of patients, contributory in 11%, but definitely misleading
      in 2%. CONCLUSIONS: FDG-PET is not required for adrenal mass diagnosis in most
      patients in contemporary practice but may help clinical decision making in
      specific situations.

PMID- 24121384
TI  - Results of the Thyroid Cancer Alliance international patient/survivor survey:
      Psychosocial/informational support needs, treatment side effects and
      international differences in care.
AB  - OBJECTIVE: To comprehensively assess the experience of a large, diverse cohort
      and identify potential care improvements, the Thyroid Cancer Alliance, an
      international patient/survivor group coalition, surveyed thyroid cancer
      patients/survivors worldwide. DESIGN: English, German, French or Spanish versions
      of a self-developed 43-item questionnaire were completed, predominantly online,
      by 2398 respondents from the US (37.9%), Germany (21.3%), the UK (11.5%), Canada
      (11.4%), France (9%), and 35 other countries. Females and differentiated thyroid
      carcinoma patients each comprised ~87% of respondents. Diagnosis occurred at age
      30-59 years in 71.8%, within <1 (1-5) year(s) before survey completion in 16.4%
      (55%). RESULTS: At diagnosis, no psychological (or other professional) support
      was offered to 92.6% (76.9%) of respondents, no patient organization referral was
      made to 84.1%, and no clear written disease/treatment information was given to
      63%. The five leading care improvement suggestions involved increased
      informational/psychosocial support. Among respondents undergoing neck surgery pre
      survey completion (n = 2380), 72.5% reported at least transient complications,
      including hypocalcemia (38.8%), voice problems (36.2%), numbness (28.7%), or
      restricted neck/shoulder movement (27.6%). CONCLUSIONS: This large,
      multinational, patient/survivor-initiated cross-sectional survey suggests that
      thyroid cancer patients/survivors have substantial unmet
      informational/psychosocial support needs and suffer frequent treatment morbidity;
      disease management and some patient/survivor experience differ appreciably among
      countries.

PMID- 24121385
TI  - Frax score calculations in postmenopausal women with subclinical hypothyroidism.
AB  - OBJECTIVE: The aim of our study was to evaluate the relationship between the
      elevated TSH and fracture risk in postmenopausal women with subclinical
      hypothyroidism for evaluation of individuals with a high risk for osteoporotic
      fractures. DESIGN: FRAX score calculation (10-year estimated risk for bone
      fracture) and measurement of bone markers (osteocalcin and beta cross-laps) were
      performed in 82 postmenopausal women with newly discovered subclinical
      hypothyroidism (mean age 59.17+/-7.07, mean BMI 27.89+/-3.46kg/m2, menopause
      onset in 48.05+/-4.09 years of age) and 51 matched controls (mean age 59.69+/
      5.72, mean BMI 27.68+/-4.66kg/m2, menopause onset in 48.53+/-4.58 years of age)
      with normal thyroid function. RESULTS: The main FRAX score was significantly
      higher in the group with subclinical hypothyroidism than in the controls (6.50+/
      4.58 vs. 4.35+/-1.56; p=0.001). Hip FRAX score was significantly higher in the
      group with subclinical hypothyroidism (1.11+/-1.94 vs. 0.50+/-0.46; p=0.030).
      There was no significant difference in bone markers: osteocalcin (23.99+/-12.63
      vs. 21.79+/-5.34 ng/mL; p=0.484) and beta cross-laps (365.76+/-184.84 vs.
      306.88+/-110.73 pg/mL; p=0.21) between the two groups. CONCLUSIONS:
      Postmenopausal patients with subclinical hypothyroidism, in particular of
      autoimmune origin, have higher FRAX scores and a thus greater risk for low-trauma
      hip fracture than euthyroid postmenopausal women. Our results point to the need
      to monitor postmenopausal patients with subclinical hypothyroidism for avoidance
      of fractures.

PMID- 24121386
TI  - Pulmonary arterial sampling was useful for localizing ectopic ACTH production in
      a patient with bronchial carcinoid causing Cushing syndrome.
AB  - OBJECTIVE: We report a 44-year old man with ectopic adrenocorticotropic hormone
      (ACTH) syndrome caused by bronchial carcinoid that developed Cushing syndrome.
      METHODS: We performed several imaging studies, including chest and abdominal CT,
      for exploration of nodules and selective pulmonary arterial sampling for
      localizing a source of ectopic ACTH production. RESULTS: The patient was
      diagnosed as Cushing syndrome due to ectopic production of ACTH without
      identification of its source(s). After 2 years' follow-up with repeated CT scans
      every 6-12 months and treatment with metyrapone, chest CT revealed two small
      nodules respectively in the segment (S) 4 and 10 of the right lung. We performed
      selective pulmonary arterial sampling from branches of the right pulmonary artery
      to obtain blood from the nodules in a reverse flow fashion: wedged sampling from
      the basal branch (A8, 9 and 10) revealed significant elevation of ACTH, whereas
      sampling from the lateral branch (A4) did not, indicating that the S10 nodule
      produced ACTH ectopically. The video-assisted thoracoscopic surgery removing the
      right inferior lobe normalized plasma ACTH, serum cortisol and 24-hour urinary
      free cortisol. The S10 nodule was histologically diagnosed as atypical bronchial
      carcinoid containing immunoreactive ACTH. CONCLUSIONS: Selective pulmonary
      arterial sampling was useful for localizing the lesion of ectopic ACTH production
      and helped make the decision for its surgical removal. This procedure should be
      considered once lung nodules suspicious for ectopic ACTH production are
      identified in patients with EAS.

PMID- 24121387
TI  - Familial isolated primary hyperparathyroidism due to HRPT2 mutation.
AB  - Primary hyperparathyroidism is a common endocrine disorder that is mostly caused
      by solitary tumors within the parathyroid glands. Characterized by early debut
      and higher frequency of multiple parathyroid masses, familial forms of primary
      hyperparathyroidism are caused by the already known mutations of: menin (MEN1
      syndrome), RET proto-oncogene (MEN2 syndrome), HRPT2-parafibromin
      (hyperparathyroidism-jaw tumor syndrome), calcium sensing receptor gene (familial
      hypocalciuric hypercalcemia). A specific mutation in FIHP has not been identified
      in the majority of affected families. Recent studies revealed menin, HRPT2 and
      calcium-sensing receptor mutations in patients with FIHP. Whether FIHP is a
      variant or an early stage of MEN1 syndrome or hyperparathyroidism-jaw tumor
      syndrome is yet to be established. We present three siblings with familial
      isolated hyperparathyroidism due to solitary parathyroid adenoma and favorable
      evolution post-parathyroidectomy. Genetic tests revealed HRPT2 mutation. 

PMID- 24121388
TI  - A case of Dyke-Davidoff-Masson syndrome associated with central hypothyroidism
      and secondary adrenal insufficiency.
AB  - A diagnosis of central hypothyroidism (CH) can be missed easily or delayed
      without a high index of suspicion due to normal or slightly altered thyroid
      stimulating hormone (TSH) levels during the initial screening test for thyroid
      dysfunction. A correct diagnosis of CH is very important for safely treating
      patients. Specifically, doctors must ensure a proper evaluation of combined
      adrenal insufficiency to prevent a fatal adrenal crisis. Here we report a case of
      CH combined with secondary adrenal insufficiency in a 42-year-old woman with Dyke
      Davidoff-Masson syndrome, which is a rare neurological disease. 

PMID- 24121389
TI  - Family history in the diagnosis of monogenic diabetes "leads and misleads".
AB  - Always granting that de novo mutations are possible, family history and
      biological characteristics are nonetheless crucial for the diagnosis of monogenic
      diabetes. We report here the case of two patients with monogenic diabetes in
      which the initial family history misled the diagnostic work-up and did not
      support the diagnosis. Family history details changed substantially after the
      molecular diagnosis was established. 

PMID- 24121390
TI  - The antiepileptic drug carbamazepine can cause adrenal insufficiency in patients
      under hormone replacement therapy for congenital adrenal hyperplasia.

PMID- 24121391
TI  - Hypertensive crisis during adrenalectomy in a patient with pheochromocytoma and a
      HOCM with SAM.

PMID- 24121392
TI  - PNA as a potential modulator of COL7A1 gene expression in dominant dystrophic
      epidermolysis bullosa: a physico-chemical study.
AB  - Dominant diseases are single gene disorders occurring in the heterozygous state.
      The mutated allele exerts a dominant effect because it produces an abnormal
      polypeptide that interferes with the function of the normal allele product.
      Peptide Nucleic Acids (PNAs) offer a route for a potential therapy for dominant
      diseases by selectively silencing the allele carrying the dominant mutation.
      Here, we have synthesized and studied the properties of a 15-mer PNA fully
      complementary to the site of the c.5272-38T>A sequence variation, which
      identifies a recurrent mutant COL7A1 allele causing dominant dystrophic
      epidermolysis bullosa (DDEB), a mendelian disease characterized by skin
      blistering. The PNA was conjugated with four lysine residues at the C-terminus
      and a fluorescent probe at the N-terminus. Physico-chemical results proved the
      formation of a stable, selective PNA/mutant-DNA heteroduplex in vitro.
      Intriguingly, when transfected into normal human fibroblasts, the PNA correctly
      localized in the cell nucleus. Our results open new therapeutic possibilities for
      patients with DDEB. 

PMID- 24121394
TI  - Mechanism of oxygen reduction reaction catalyzed by Fe(Co)-Nx/C.
AB  - Fe(Co)-Nx/C is an important candidate catalyst for the next generation proton
      exchange membrane fuel cells (PEMFC), but the relationship between the structure
      and the oxygen reduction activity is still unclear. In this work, the different
      active site structures of Fe(Co)-Nx/C are explored and the oxygen reduction
      catalytic mechanisms are studied by means of density functional theory (DFT).
      Different kinds of Me-Nx/C motifs, including the edge site around the graphene
      sheet and the internal site in the graphene sheet (as well as in the graphyne
      sheet), are constructed and investigated. The calculated results suggest that for
      the edge active sites, high O2 adsorption strength may result in direct oxidation
      of metal ions thus losing their catalytic activity. The internal active sites are
      stable in acidic solution and display catalytic ability of oxygen reduction. The
      catalytic activity of the internal site is affected by three factors: the kind of
      internal metal ion, the bonded nitrogen or carbon atoms with metal ions and the
      size of the graphene sheet. 

PMID- 24121393
TI  - Pediatric adiposity stabilized in Switzerland between  1999 and 2012.
AB  - PURPOSE: Several countries have recently reported stabilization and/or a decrease
      in the prevalence of pediatric obesity. However, systematic, repeated national
      monitoring studies are scarce, and it is unclear whether this trend would be
      sustained. The objective was to present the latest overweight and obesity
      prevalence in Swiss children and to investigate trends in prevalence from 1999 to
      2012. METHODS: Using probability-proportionate-to-size cluster sampling,
      nationally representative samples of children aged 6-12 years were recruited in
      1999 (n = 594), 2002 (n = 2,493), 2004 (n = 328), 2007 (n = 2,218), 2009 (n =
      907), and 2012 (n = 2,963). Height and weight were measured to calculate BMI
      (kg/m2). BMI cutoffs proposed by the Centers for Disease Control and Prevention
      (CDC) and by the International Obesity Task Force were used to determine the
      prevalence of overweight (excluding obesity) and obesity. Waist circumference was
      measured in 2007 and 2012, and multiple skinfold thicknesses assessed in 2002 and
      2012. RESULTS: Using the CDC criteria, prevalences of overweight and obesity in
      2012 were 11.9 % (95 % CI 10.7-13.1) and 7.1 % (95 % CI 6.2-8.0), respectively,
      and did not change between 1999 and 2012 (beta = -0.144, p = 0.293 and beta = 
      0.063, p = 0.552, respectively). Boys had significantly higher obesity prevalence
      than girls in 2007 (5.6 vs. 3.4 %) and 2012 (8.1 vs. 5.9 %). Percentage of
      children with excess waist circumference and body fat percentage did not differ
      between 2007 and 2012, and 2002 and 2012, respectively. CONCLUSION: Our data
      indicate the prevalence of childhood adiposity in Switzerland stabilized between
      1999 and 2012, but ~1 in 5 children remain overweight or obese and further
      efforts are needed to control the epidemic.

PMID- 24121395
TI  - The extraction controversy.

PMID- 24121396
TI  - Class II therapy with a combination of customized lingual appliances and the
      Forsus device.

PMID- 24121397
TI  - Treatment of severe facial asymmetry using virtual three-dimensional planning and
      a "surgery first" protocol.

PMID- 24121398
TI  - Correction of malpositioned lower lateral incisors in a two-phase nonextraction
      case.

PMID- 24121399
TI  - Prediction of maxillary lateral-incisor root resorption using sector analysis of
      potentially impacted canines.

PMID- 24121400
TI  - Consequences of poor oral hygiene during aligner therapy.

PMID- 24121401
TI  - Designing randomized-controlled trials to improve head-louse treatment:
      systematic review using a vignette-based method.
AB  - Head-louse infestation remains a public health problem. Despite published
      randomized-controlled trials, no consensus-based clinical practice guidelines for
      its management emerged because of the heterogeneity of trial methodologies. Our
      study was undertaken to attempt to find an optimal trial framework: minimizing
      the risk of bias, while taking feasibility into account. To do so, we used the
      vignette-based method. A systematic review first identified trials on head-louse
      infestation; 49 were selected and their methodological constraints assessed.
      Methodological features were extracted and combined by arborescence to generate a
      broad spectrum of potential designs, called vignettes, yielding 357 vignettes. A
      panel of 48 experts then rated one-on-one comparisons of those vignettes to
      obtain a ranking of the designs. Methodological items retained for vignette
      generation were income level of the population, types of treatments compared,
      randomization unit, blinding, treatment-administration site, diagnosis method and
      criteria, and primary outcome measure. The expert panel selected vignettes with
      cluster randomization, centralized treatment administration, and blinding of the
      outcome assessor. The vignette method identified optimal designs to standardize
      future head-louse treatment trials, thereby obtaining valid conclusions and
      comparable data from future trials, and appears to be a reliable way to generate
      evidence-based guidelines. 

PMID- 24121402
TI  - Crosstalk between keratinocytes and T cells in a 3D microenvironment: a model to
      study inflammatory skin diseases.
AB  - The interaction between keratinocytes and immune cells plays a major role in the
      development of inflammatory skin diseases like psoriasis and atopic dermatitis.
      Pharmacological intervention to inhibit T cell-derived proinflammatory mediators
      is an effective therapy in the treatment of psoriasis. Here, we present a model
      to study the interaction between keratinocytes and T cells in a three-dimensional
      (3D) microenvironment, based on human skin equivalents populated with CD4+ T
      cells. T cell migration into the dermis initiated keratinocyte activation within
      2 days, with hallmarks of a psoriasiform inflammation after 4 days. Expression of
      epidermal psoriasis marker genes was upregulated, and proinflammatory cytokines
      and chemokines were highly expressed. Disturbed epidermal differentiation was
      shown by downregulated filaggrin expression and involucrin expression in the
      spinous layer. These effects were mediated via soluble factors produced by the T
      cells. The psoriasiform inflammation was also observed using T helper type 1
      (Th1)- and Th17-polarized CD4+ T cells. We validated our model by treatment with
      anti-inflammatory drugs that reduced the expression of proinflammatory cytokines
      and chemokines and suppressed the psoriasiform inflammation. We propose that our
      T cell-driven inflammatory skin equivalent model has potential to study the
      pathogenesis of inflammatory skin diseases and may serve as a preclinical
      screening tool for anti-inflammatory drugs. 

PMID- 24121403
TI  - Skin fragility and impaired desmosomal adhesion in mice lacking all keratins.
AB  - Keratins perform major structural and regulatory functions in epithelia. Owing to
      redundancy, their respective contribution to epidermal integrity, adhesion, and
      cell junction formation has not been addressed in full. Unexpectedly, the
      constitutive deletion of type II keratins in mice was embryonic lethal ~ E9.5
      without extensive tissue damage. This prompted us to analyze keratin functions in
      skin where keratins are best characterized. Here, we compare the mosaic and
      complete deletion of all type II keratins in mouse skin, with distinct
      consequences on epidermal integrity, adhesion, and organismal survival. Mosaic
      knockout (KO) mice survived ~ 12 days while global KO mice died perinatally
      because of extensive epidermal damage. Coinciding with absence of keratins,
      epidermal fragility, inflammation, increased epidermal thickness, and increased
      proliferation were noted in both strains of mice, accompanied by significantly
      smaller desmosomes. Decreased desmosome size was due to accumulation of
      desmosomal proteins in the cytoplasm, causing intercellular adhesion defects
      resulting in intercellular splits. Mixing different ratios of wild-type and KO
      keratinocytes revealed that ~ 60% of keratin-expressing cells were sufficient to
      maintain epithelial sheets under stress. Our data reveal a major contribution of
      keratins to the maintenance of desmosomal adhesion and epidermal integrity with
      relevance for the treatment of epidermolysis bullosa simplex and other
      keratinopathies.

PMID- 24121405
TI  - The effect of optical blur on central and peripheral word visual acuity.
AB  - PURPOSE: We investigated how dioptric blur affected word acuity thresholds for
      targets presented at different retinal eccentricities. METHODS: Word thresholds
      were measured at 0, 5, and 10 degrees and for different Weber contrast levels of
      4, 10, 45, and 90%. RESULTS: We find that increasing optical blur increased word
      acuity thresholds, but the extent of change was dependent on retinal eccentricity
      and stimulus contrast. In particular, the resolution reduction per diopter of
      blur (as indicated by the slope of lines fitted to data) was significantly less
      at peripheral locations (0 degrees vs. 5 and 10 degrees) and for low-contrast
      targets. CONCLUSIONS: These findings provide useful guidelines to predict how
      patients with contrast loss and/or those that rely upon an eccentric retinal
      location for reading respond to the introduction of optical blur in a clinical
      setting.

PMID- 24121404
TI  - Catecholamine stress alters neutrophil trafficking and impairs wound healing by
      beta2-adrenergic receptor-mediated upregulation of IL-6.
AB  - Stress-induced hormones can alter the inflammatory response to tissue injury;
      however, the precise mechanism by which epinephrine influences inflammatory
      response and wound healing is not well defined. Here we demonstrate that
      epinephrine alters the neutrophil (polymorphonuclear leukocyte (PMN))-dependent
      inflammatory response to a cutaneous wound. Using noninvasive real-time imaging
      of genetically tagged PMNs in a murine skin wound, chronic, epinephrine-mediated
      stress was modeled by sustained delivery of epinephrine. Prolonged systemic
      exposure of epinephrine resulted in persistent PMN trafficking to the wound site
      via an IL-6-mediated mechanism, and this in turn impaired wound repair. Further,
      we demonstrate that beta2-adrenergic receptor-dependent activation of
      proinflammatory macrophages is critical for epinephrine-mediated IL-6 production.
      This study expands our current understanding of stress hormone-mediated
      impairment of wound healing and provides an important mechanistic link to explain
      how epinephrine stress exacerbates inflammation via increased number and lifetime
      of PMNs. 

PMID- 24121406
TI  - Accommodative responses under different stimulus conditions.
AB  - PURPOSE: The method and the sequence of accommodative stimuli are two factors
      affecting the steady-state accommodative response. This study investigated the
      possible effects of these two factors on the accommodative stimulus response
      curves (ASRCs) and compared three indexes to evaluate ASRC in the different
      stimulus conditions. METHODS: In this study, we investigated the difference in
      the accommodative stimulus response curves under six stimulus conditions. The
      ASRCs of 10 emmetropes were measured when the accommodative stimulus (AS) was
      induced using three methods: negative lenses, positive lenses, and a Badal
      stimulator; and the stimulus was presented using two sequences: ascending and
      descending sequences. Three indexes, accommodative error area (AEA),
      accommodative error index (AEI), and the slope of ASRC, were used for comparison.
      RESULTS: The accommodative error was larger when accommodative stimulus was
      presented in the ascending sequence than in the descending sequence (p < 0.05) in
      the Badal stimulator method whenever AEI, AEA, or the slope of ASRC was used. The
      ASRCs elicited with positive lenses were more accurate than that elicited with
      negative lenses or the Badal stimulator when AEA and AEI were used. However, when
      the slope of the ASRC was used, the result was not significant. CONCLUSIONS: The
      results suggest that the accommodative response in the steady state may be
      affected by the method used for inducing AS and the sequence of AS presented. The
      AEA is suggested to be used in the evaluation of the accuracy of the ASRC in
      future studies.

PMID- 24121407
TI  - Correlating perimetric indices with three nerve fiber layer thickness measures.
AB  - PURPOSE: To determine which of three estimates of retinal nerve fiber layer
      thickness (RNFLT) correlate best with visual field sensitivity measured using
      standard automated perimetry (SAP). METHODS: Data were collected from 400 eyes of
      209 participants enrolled in the Portland Progression Project. These individuals
      ranged from high-risk suspects to having non-end-stage glaucoma. In each eye,
      three measures of average RNFLT (spectral domain optical coherence tomography
      [SDOCT], scanning laser polarimetry [SLP], confocal scanning laser tomography
      [CSLT]) and SAP (Humphrey HFAII) were performed on the same day. Mean deviation
      (MD), mean sensitivity (MS), and pattern standard deviation (PSD) were linearized
      using the equations MD(Lin) = 10(MD*0.1), MS(Lin) = 10(MS*0.1), and PSD(Lin) =
      10(PSD*-0.1). Correlations between each of the estimates of RNFLT and each of the
      functional metrics were calculated (nine total). Pearson correlations and
      generalized estimating equations (GEE) were used to calculate the strength and
      significance of the correlations. RESULTS: Linearized MS had the strongest
      correlation with SDOCT (r = 0.57), intermediate with SLP (r = 0.40), and weakest
      with CSLT (r = 0.13). When multiple RNFLT measures were included in a GEE model
      to predict MS(Lin), SDOCT was consistently predictive (p < 0.001) whereas CSLT
      was never predictive in these multivariate models. Similar findings were observed
      for MD(Lin) and PSD(Lin). CONCLUSIONS: Average RNFLT estimated from SDOCT
      predicts SAP status significantly better than average RNFLT estimated from SLP or
      CSLT.

PMID- 24121409
TI  - A case of Schnyder corneal dystrophy with crystals.
AB  - PURPOSE: To report a rare corneal dystrophy and its common findings to help aid
      others in proper and early diagnosis and management. CASE REPORT: A 56-year-old
      male patient presented with the concern of blurry vision in both eyes that has
      progressed over the last 10 years. Anterior segment examination revealed arcus
      with a central haze in both eyes and crystalline deposition in the right eye. A
      diagnosis of Schnyder corneal dystrophy was made based on clinical presentation.
      CONCLUSIONS: Schnyder corneal dystrophy is rare but has different presentations
      and may actually be misdiagnosed. The clinical signs change as the patient ages
      causing a decrease in vision, which may necessitate referral for phototherapeutic
      keratectomy, penetrating keratoplasty or deep anterior lamellar keratoplasty. The
      patient's systemic findings that correlate with the dystrophy need to be assessed
      and managed appropriately.

PMID- 24121408
TI  - Comparison of OCT measurements between high myopic and low myopic children.
AB  - PURPOSE: To compare the peripapillary retinal nerve fiber layer (RNFL) thickness,
      macular thickness, and total macular volume of high myopic eyes with those of low
      myopic eyes in children younger than 10 years. METHODS: Prospective, randomized,
      comparative study. Time-domain optical coherence tomography (OCT) (Stratus OCT;
      Carl Zeiss Meditec) was performed on 15 children with high myopia (refractive
      error greater than or equal to -6.0 diopters [D], group 1) and 20 children with
      low myopia (0 less than refractive error from -0.25 to -3.0 D, group 2). Fast
      RNFL scan and a fast macular scan with OCT were performed in both groups. The
      authors compared the data between the two groups. RESULTS: The mean age of the
      patients with high myopia was 7.8 years and that of those with low myopia was 7.2
      years. The mean overall thickness of the peripapillary RNFL was 100.8 MUm in the
      high myopes and 110.5 MUm in the low myopes. There was a statistically
      significant difference in the overall RNFL thickness between the two groups (p <
      0.05). In addition, peripapillary RNFL thinning was especially prominent in the
      inferior quadrant in children with high myopia (p = 0.021). The mean values of
      macula thickness and volume for high myopes were also significantly smaller than
      the mean values for low myopes (p < 0.05). CONCLUSIONS: The inferior quadrant and
      the overall peripapillary RNFL were significantly thinner in high myopic children
      relative to low myopic children. High myopic children had significantly thinner
      macular thickness and lower macular volumes. These structural differences should
      be considered in the clinical assessment of high myopic children.

PMID- 24121410
TI  - Self-assembly of interfacial and photoactive layers via one-step solution
      processing for efficient inverted organic solar cells.
AB  - Vertically self-assembled bilayers with an interfacial bottom layer and a
      photoactive top layer are demonstrated via a single coating step of a blend
      composed of an amine-containing nonconjugated polyelectrolyte (NPE) and an
      organic electron donor-acceptor bulk heterojunction composite. The self-assembled
      NPE layer reduces the work function of an indium tin oxide (ITO) cathode, which
      leads to efficient inverted organic solar cells without any additional interface
      engineering of the ITO. 

PMID- 24121411
TI  - Theoretical study on superalkali (Li3) in ammonia: novel alkalides with
      considerably large first hyperpolarizabilities.
AB  - Superalkali Li3 dissolved in gaseous ammonia is investigated by density
      functional theory. Similar to the lithium atom, Li3 can coordinate up to four
      ammonia molecules. Among the structural isomers of Li3(NH3)n (n = 1-4), the one
      with separately distributed NH3 ligands is preferred. Most of the Li3(NH3)n
      species possess the alkalide characteristics and exhibit considerably large
      static first hyperpolarizabilities (beta0) up to 3.9 * 10(5) au. Especially, for
      the lowest-energy Li3(NH3)n complexes, a prominent coordination number dependence
      of beta0 is found as follows: 12 608 (n = 1) < 38 564 (n = 2) < 121 726 (n = 3) <
      391 149 au (n = 4). In addition, the case of introducing a Na atom into such
      superalkali-ammonia systems has been considered and the resulting Li3(NH3)nNa (n
      = 1-4) complexes are studied in the same vein. It is revealed that the beta0
      values of Li3(NH3)nNa are influenced by both the coordination number and the
      relative position of NH3 ligands. We hope that this study could provide a new
      type of alkalides and raise the possibility of exploring a fresh, thriving area,
      i.e. superalkali solutions with solvents of all sorts. 

PMID- 24121412
TI  - Shaping attention with reward: effects of reward on space- and object-based
      selection.
AB  - The contribution of rewarded actions to automatic attentional selection remains
      obscure. We hypothesized that some forms of automatic orienting, such as object
      based selection, can be completely abandoned in favor of a reward-maximizing
      strategy. In the two experiments reported here, we presented identical visual
      stimuli to observers while manipulating what was being rewarded (targets in
      different locations from the cue or in random object locations) and the type of
      reward received (money or points). We found that reward alone, not the objects,
      guides attentional selection and thus entirely predicts behavior. These results
      suggest that guidance of selective attention, although automatic, is flexible and
      can be adjusted in accordance with external nonsensory reward-based factors. 

PMID- 24121413
TI  - The price of racial bias: intergroup negotiations in the ultimatum game.
AB  - Existing stereotypes about Black Americans may influence perceptions of intent
      during financial negotiations. In this study, we explored whether the influence
      of race on economic decisions extends to choices that are costly to the decision
      maker. We investigated whether racial group membership contributes to
      differential likelihood of rejection of objectively equal unfair monetary offers.
      In the Ultimatum Game, players accept or reject proposed splits of money. Players
      keep accepted splits, but if a player rejects an offer, both the player and the
      proposer receive nothing. We found that participants accepted more offers and
      lower offer amounts from White proposers than from Black proposers, and that this
      pattern was accentuated for participants with higher implicit race bias. These
      findings indicate that participants are willing to discriminate against Black
      proposers even at a cost to their own financial gain. 

PMID- 24121414
TI  - Beauty at the ballot box: disease threats predict preferences for physically
      attractive leaders.
AB  - Why does beauty win out at the ballot box? Some researchers have posited that it
      occurs because people ascribe generally positive characteristics to physically
      attractive candidates. We propose an alternative explanation-that leadership
      preferences are related to functional disease-avoidance mechanisms. Because
      physical attractiveness is a cue to health, people concerned with disease should
      especially prefer physically attractive leaders. Using real-world voting data and
      laboratory-based experiments, we found support for this relationship. In
      congressional districts with elevated disease threats, physically attractive
      candidates are more likely to be elected (Study 1). Experimentally activating
      disease concerns leads people to especially value physical attractiveness in
      leaders (Study 2) and prefer more physically attractive political candidates
      (Study 3). In a final study, we demonstrated that these findings are related to
      leadership preferences, specifically, rather than preferences for physically
      attractive group members more generally (Study 4). Together, these findings
      highlight the nuanced and functional nature of leadership preferences. 

PMID- 24121415
TI  - Information matching the content of visual working memory is prioritized for
      conscious access.
AB  - Visual working memory (VWM) is used to retain relevant information for imminent
      goal-directed behavior. In the experiments reported here, we found that VWM helps
      to prioritize relevant information that is not yet available for conscious
      experience. In five experiments, we demonstrated that information matching VWM
      content reaches visual awareness faster than does information not matching VWM
      content. Our findings suggest a functional link between VWM and visual awareness:
      The content of VWM is recruited to funnel down the vast amount of sensory input
      to that which is relevant for subsequent behavior and therefore requires
      conscious access. 

PMID- 24121416
TI  - Examining the evidence: reporter identity, allegation type, and sociodemographic
      characteristics as predictors of maltreatment substantiation.
AB  - Using linked administrative data from child protection and birth records in
      California, this study examined whether the mandated status and type of reporter
      are independent predictors of substantiation among infants and young children
      across maltreatment types and after adjusting for characteristics of the child
      and family. Of the 59,413 children born in 2002 who were reported and
      investigated for maltreatment before the age of 5 years, 26% were substantiated.
      Reports originating from mandated sources were 2.5 times as likely (95%
      confidence interval, CI [2.40, 2.60]) to be substantiated as those from
      nonmandated reporters. Findings demonstrated that children whose allegations were
      reported by law enforcement, medical professionals, and workers in public
      agencies were consistently substantiated at higher rates than allegations from
      other mandated reporters. Results also indicated that the relationship between
      reporter type and the likelihood of substantiation varied by maltreatment type.
      Children reported by law enforcement for physical abuse were 6.3 times as likely
      (95% CI [4.86, 8.04]) to be substantiated as those reported by nonmandated
      sources. 

PMID- 24121417
TI  - Regulation of flavanone 3-hydroxylase gene involved in the flavonoid biosynthesis
      pathway in response to UV-B radiation and drought stress in the desert plant,
      Reaumuria soongorica.
AB  - Flavonoid are known to have various functions in growth, development,
      reproduction, and also involved in diverse stress responses in plants. However,
      little is known about the roles of the key enzymes in the flavonoid biosynthetic
      pathway in response to environmental stress, such as UV-B radiation and drought.
      To understand this problem, we investigated the participation of flavanone 3
      hydroxylase gene (F3H), a key enzyme in flavonoid biosynthetic pathway under UV-B
      radiation and drought stress in the desert plant Reaumuria soongorica. A novel
      cDNA sequence, named as RsF3H, was isolated from R. soongorica. The deduced amino
      acids showed high identities to other F3Hs. A phylogenetic analysis indicated
      that RsF3H appeared to be most homologous to F3H from Malus domestica (MdF3H).
      RsF3H protein structure contained all five conserved motifs for 2-oxoglutarate
      dependent dioxygenases (2-ODDs) and an Arg-X-Ser motif, all of which were also
      found in other F3Hs. Quantitative real-time RT-PCR analysis showed that there was
      a rapid increase in gene expression of RsF3H under stress. Both UV-B radiation
      and drought stress induced an increase in RsF3H enzyme activity and the
      accumulation of the products in the flavonoid biosynthetic pathway (total
      flavonoid and anthocyanin). The antioxidant ability (inhibition of lipid
      oxidation) of total flavonoid was enhanced during this study. The results
      suggested that one explanation of the stress tolerance of R. soongorica may be a
      combination of an increase in RsF3H gene expression, RsF3H enzyme activity and
      the anti-oxidative ability of the metabolic end products in the flavonoid
      biosynthetic pathway in response to UV-B radiation and drought. 

PMID- 24121418
TI  - The effect of humic acids on biodegradation of polycyclic aromatic hydrocarbons
      depends on the exposure regime.
AB  - Binding of polycyclic aromatic hydrocarbons (PAHs) to dissolved organic matter
      (DOM) can reduce the freely dissolved concentration, increase apparent solubility
      or enhance diffusive mass transfer. To study the effects of DOM on
      biodegradation, we used phenanthrene and pyrene as model PAHs, soil humic acids
      as model DOM and a soil Mycobacterium strain as a representative degrader
      organism. Humic acids enhanced the biodegradation of pyrene when present as solid
      crystals but not when initially dissolved or provided by partitioning from a
      polymer. Synchronous fluorescence spectrophotometry, scintillation counting and a
      microscale diffusion technique were applied in order to determine the kinetics of
      dissolution and diffusive mass transfer of pyrene. We suggest that humic acids
      can enhance or inhibit biodegradation as a result of the balance of two opposite
      effects, namely, solubilization of the chemicals on the one hand and inhibition
      of cell adhesion to the pollutant source on the other. 

PMID- 24121419
TI  - Plant growth responses to inorganic environmental contaminants are density
      dependent: experiments with copper sulfate, barley and lettuce.
AB  - The density-dependence of terrestrial plant-plant interactions in the presence of
      toxins has previously been explored using biodegradable compounds. We exposed
      barley and lettuce to four copper concentrations at four stand densities. We
      hypothesized that toxin effects would decrease and Cu uptake would increase at
      increasing plant densities. We analyzed toxin effects by (a) comparing plant
      biomasses and (b) using a recent regression model that has a separate parameter
      for the interaction of resource competition and toxin interference. Plant
      response to Cu was density-dependent in both experiments. Total Cu uptake by
      barley increased and the dose per plant decreased as plant density increased.
      This study is the first to demonstrate that plant density mediates plant response
      to metals in soil in a predictable way. This highlights the need to explore the
      mechanisms for and consequences of these effects, and to integrate the use of
      several plant densities into standard ecotoxicological testing. 

PMID- 24121420
TI  - Application of congener based multi-matrix profiling techniques to identify
      potential PCDD/F sources in environmental samples from the Burrishoole Catchment
      in the West of Ireland.
AB  - Homologue and congener profiles of PCDD/Fs in eels, passive sampler and sediment
      extracts from the Burrishoole, a rural upland catchment on the western Irish
      seaboard were compared with potential PCDD sources. SigmaPCDD/F levels in eels
      ranged from 2.9 to 25.9 pg g(-1) wet weight, which are elevated compared to other
      Irish locations. The OCDD congener dominated the pattern of SigmaPCDD/Fs in all
      matrices from Burrishoole. Passive samplers were successfully deployed to
      identify for the first time the presence in the water column of PCDD/Fs and
      dimethoxylated octachlorodiphenyl ether (diMeOoctaCDE), impurities found in
      pentachlorophenol (PCP) production. Principal component analysis (PCA) identified
      similarities between PCDD/F profiles in technical PCP mixtures and environmental
      samples from the Burrishoole region. Results strongly suggest residual PCDD
      contamination associated with historic local use of a dioxin contaminated product
      in the catchment area, with pentachlorophenol a strong candidate. 

PMID- 24121421
TI  - Seasonal ozone uptake by a warm-temperate mixed deciduous and evergreen broadleaf
      forest in western Japan estimated by the Penman-Monteith approach combined with a
      photosynthesis-dependent stomatal model.
AB  - Canopy-level stomatal conductance over a warm-temperate mixed deciduous and
      evergreen broadleaf forest in Japan was estimated by the Penman-Monteith
      approach, as compensated by a semi-empirical photosynthesis-dependent stomatal
      model, where photosynthesis, relative humidity, and CO2 concentration were
      assumed to regulate stomatal conductance. This approach, using eddy covariance
      data and routine meteorological observations at a flux tower site, permits the
      continuous estimation of canopy-level O3 uptake, even when the Penman-Monteith
      approach is unavailable (i.e. in case of direct evaporation from soil or wet
      leaves). Distortion was observed between the AOT40 exposure index and O3 uptake
      through stomata, as AOT40 peaked in April, but with O3 uptake occurring in July.
      Thus, leaf pre-maturation in the predominant deciduous broadleaf tree species
      (Quercus serrata) might suppress O3 uptake in springtime, even when the highest
      O3 concentrations were observed.

PMID- 24121422
TI  - Release and environmental impact of silver nanoparticles and conventional organic
      biocides from coated wooden facades.
AB  - This study represents for the first time a comprehensive assessment of
      functionality and environmental impacts of metallic silver nanoparticles (Ag-NP)
      compared to conventional organic biocides. Four different transparent,
      hydrophobic coatings of wooden outdoor facades were tested during one year
      outdoor weathering. The total silver release from products with Ag-NP was
      proportional to the overall erosion of the coating. The results indicate that the
      Ag-NPs are likely transformed to silver complexes, which are considerably less
      toxic than ionic silver. The protective effect of the silver containing coatings
      against mold, blue stain and algae was insufficient, even in immaculate and non
      weathered conditions. The release of organic biocides from conventional coatings
      was dependent on the weather conditions, the type of biocide and the use in the
      base or top coat. The conventional coating showed a good overall performance free
      from mold, blue stain and algae until the end of the test period. 

PMID- 24121423
TI  - Insulator-metal transition of VO2 ultrathin films on silicon: evidence for an
      electronic origin by infrared spectroscopy.
AB  - We report on the first simultaneous observations of both electronic and
      structural temperature-induced insulator-to-metal transition (IMT) in VO2
      ultrathin films, made possible by the use of broad range transmission infrared
      spectroscopy. Thanks to these techniques, the infrared phonon structures, as well
      as the appearance of the free carrier signature, were resolved for the first
      time. The temperature-resolved spectra allowed the determination of the
      temperature hysteresis for both the structural (monoclinic-to-rutile) and
      electronic (insulator-to-metallic) transitions. The combination of these new
      observations and DFT simulations for the monoclinic structure allows us to verify
      the direct transition from monoclinic (M1) to rutile and exclude an intermediate
      structural monoclinic form (M2). The delay in structural modification compared to
      the primer electronic transition (325 K compared to 304 K) supports the role of
      free charges as the transition driving force. The shape of the free charge
      hysteresis suggests that the primer electronic transition occurs first at 304 K,
      followed by both its propagation to the heart of the layer and the structural
      transition when T increases. This study outlines further the potential of VO2
      ultrathin films integrated on silicon for optoelectronics and microelectronics.

PMID- 24121424
TI  - Reovirus type-2-triggered autoimmune cholangitis in extrahepatic bile ducts of
      weanling DBA/1J mice.
AB  - BACKGROUND: Reovirus is a proposed cause of infantile biliary atresia. However,
      mechanistic insight regarding Reo-2 as a potential cholangiotropic virus is
      lacking. Furthermore, it is unknown whether Reo-2 infection can induce autoimmune
      mediated bile duct injury. METHODS: Lesions of bile ducts in newborn DBA/1J mice
      infected with Reo-2 were analyzed immunopathologically. RESULTS: Damage to
      biliary epithelia occurs after Reo-2 infection. In addition, nonsuppurative
      cholangitis with fibrosis in extrahepatic (especially septal) bile ducts
      developed following complete viral clearance from the liver. At the inflamed
      ducts, major histocompatibility complex class I expressing((+)) and FAS(+)
      cholangiocytes were associated with FAS ligand(+) lymphocytes and tumor necrosis
      factor-alpha(+) mononuclear cells (macrophages and lymphocytes). These
      cholangiocytes were apoptotic and necrotic. Moreover, affected ducts were
      infiltrated by CD3(+), CD4(+), CD8(+), IFN-gamma(+), and FAS(+) lymphocytes.
      Analysis of blood from Reo-2-infected mice revealed that they developed
      anticholangiocyte cytoplasm antibodies and had high serum IFN-gamma
      concentration. Notably, there was no increase in Foxp3(+) lymphocytes at inflamed
      ducts, lymph nodes, and thymi. CONCLUSION: Reo-2 infection induced T-helper cell
      type 1-dependent injury to bile ducts in weanling mice. The lesions observed in
      mice may be analogous to those associated with human infantile biliary atresia,
      which are caused by an autoimmune-mediated process.

PMID- 24121425
TI  - Vitamin D status among preterm and full-term infants at birth.
AB  - BACKGROUND: Risk factors for maternal vitamin D deficiency and preterm birth
      overlap, but the distribution of 25-hydroxyvitamin D (25(OH)D) levels among
      preterm infants is not known. We aimed to determine the associations between
      25(OH)D levels and gestational age. METHODS: We measured umbilical cord plasma
      levels of 25(OH)D from 471 infants born at Brigham and Women's Hospital in
      Boston. We used generalized estimating equations to determine whether preterm
      (<37 wks' gestation) or very preterm (<32 wks' gestation) infants had greater
      odds of having 25(OH)D levels below 20 ng/ml than more mature infants. We
      adjusted for potential confounding by season of birth, maternal age, race,
      marital status, and singleton or multiple gestation. RESULTS: Mean cord plasma
      25(OH)D level was 34.0 ng/ml (range: 4.1-95.3 and SD: 14.1). Infants born before
      32 wks' gestation had increased odds of having 25(OH)D levels below 20 ng/ml in
      unadjusted (odds ratio (OR): 2.2; 95% confidence interval (CI): 1.1-4.3) and
      adjusted models (OR: 2.4; 95% CI: 1.2-5.3) as compared with more mature infants.
      CONCLUSION: Infants born in <32 wks' gestation are at higher risk than more
      mature infants for low 25(OH)D levels. Further investigation of the relationships
      between low 25(OH)D levels and preterm birth and its sequelae is thus warranted.

PMID- 24121426
TI  - Synergistic protective effects of mizoribine and angiotensin II receptor blockade
      on cyclosporine A nephropathy in rats.
AB  - BACKGROUND: Chronic cyclosporine A (CsA) nephrotoxicity is manifested by renal
      dysfunction, progressive histopathological kidney lesions characterized by
      afferent arteriolopathy, and tubulointerstitial fibrosis. In addition to the
      direct toxic effect of CsA, many other etiological factors such as angiotensin
      II, transforming growth factor (TGF)-beta, and macrophage infiltration are
      involved in this pathogenesis. This study investigated the hypothesis that
      concomitant administration of mizoribine (MZR) and angiotensin II receptor
      blockade (ARB) may prevent CsA nephrotoxicity in rats. METHODS: Sprague-Dawley
      male rats were divided into the following seven groups: group 1, treated with
      CsA; group 2, treated with CsA + MZR; group 3, treated with CsA + valsartan
      (Val); group 4, treated with CsA + MZR + Val; group 5, treated with MZR; group 6,
      treated with Val; and group 7, controls (n = 5 each). Renal histopathology and
      the effect of CsA-induced nephrotoxicity on inflammatory mediators were
      evaluated. RESULTS: Results of this study demonstrated that ARB administration
      significantly decreased arteriolopathy and that in comparison with monotherapy,
      concomitant administration of MZR and ARB further decreased arteriolopathy,
      fibrosis, macrophage infiltration, and TGF-beta1 mRNA expression associated with
      CsA nephrotoxicity. CONCLUSION: These findings indicate that MZR and ARB
      combination treatment provides synergistic protective effects against chronic CsA
      nephrotoxicity.

PMID- 24121427
TI  - A highly sensitive long-wavelength fluorescence probe for nitroreductase and
      hypoxia: selective detection and quantification.
AB  - A novel long-wavelength fluorescence probe has been developed for the detection
      of nitroreductase (NTR) and hypoxia. could be activated by NTR at 0.1 MUM to
      release the fluorophore and significant changes in fluorescence emission at 658
      nm were observed. This feature makes it advantageous for imaging hypoxic cells
      with minimal endogenous interference. 

PMID- 24121428
TI  - Mortality in the coronary care unit.
AB  - OBJECTIVES: Currently, there are limited data on mortality or predictors of
      survival for patients admitted to the coronary care unit (CCU). The purpose of
      this study was to provide data on mortality in the modern-day CCU and to better
      define factors influencing patient survival. METHODS: A survey was conducted of
      all patients admitted to CCUs in New York City metropolitan academic hospitals in
      2011, followed by a retrospective analysis comparing clinical data from 59
      nonsurvivors with those from 897 survivors at two representative institutions.
      RESULTS: The weighted average mortality in the CCU across all hospitals was 5.6%
      (range 2.2-9.2%). The average age of the patients admitted to the CCU was 67
      years, with 68% being male. Acute coronary syndromes accounted for 57% of all CCU
      admissions. Survival was worse in patients admitted for cardiac arrest (P=0.000),
      sepsis (P=0.002), primary respiratory failure (P=0.031), and systolic heart
      failure (P=0.003). Excluding patients who were made 'do not resuscitate' during
      their CCU stay, patients receiving treatments such as defibrillation after in-CCU
      cardiac arrest, right heart invasive monitoring, mechanical ventilation,
      inotropic support, emergent dialysis, or placement of an intra-aortic balloon
      pump had higher rates of in-CCU mortality. The most frequent causes of death were
      intractable cardiogenic shock, brain death, respiratory failure, multiorgan
      failure, or hypotension. CONCLUSION: This study provides additional mortality
      information for the modern-day CCU and should help identify factors that may
      predict survival.

PMID- 24121430
TI  - Preparation of Fe(3)O(4)@C@CNC multifunctional magnetic core/shell nanoparticles
      and their application in a signal-type flow-injection photoluminescence
      immunosensor.
AB  - We describe here the preparation of carbon-coated Fe3O4 magnetic nanoparticles
      that were further fabricated into multifunctional core/shell nanoparticles
      (Fe3O4@C@CNCs) through a layer-by-layer self-assembly process of carbon
      nanocrystals (CNCs). The nanoparticles were applied in a photoluminescence (PL)
      immunosensor to detect the carcinoembryonic antigen (CEA), and CEA primary
      antibody was immobilized onto the surface of the nanoparticles. In addition, CEA
      secondary antibody and glucose oxidase were covalently bonded to silica
      nanoparticles. After stepwise immunoreactions, the immunoreagent was injected
      into the PL cell using a flow-injection PL system. When glucose was injected,
      hydrogen peroxide was obtained because of glucose oxidase catalysis and quenched
      the PL of the Fe3O4@C@CNC nanoparticles. The here proposed PL immunosensor
      allowed us to determine CEA concentrations in the 0.005-50 ng.mL-1 concentration
      range, with a detection limit of 1.8 pg.mL-1.

PMID- 24121431
TI  - Quantification of an intact monoclonal antibody, rituximab, by (RP)HPLC/DAD in
      compliance with ICH guidelines.
AB  - We studied the quantification of an intact therapeutic monoclonal antibody (mAb),
      rituximab (RTX), using (reversephase) high-performance liquid chromatography with
      diode array detection ((RP)HPLC/DAD). To this end, we developed a chromatographic
      method and validated it as stabilityindicating in accordance with the
      International Conference on Harmonization guidelines (ICH). A 300-A C8 column
      (250 mm*4.6 mm, 5 MUm) was used to perform the analysis, and the temperature was
      maintained at 70  degrees C. Although only one mAb was analyzed, it was necessary
      to apply a gradient to elute it with a complex organic mixture. Chromatograms
      were registered at several wavelengths, with lambda =214 nm employed for
      quantification purposes. The method was developed to quantify marketed RTX under
      typical hospital administration conditions. Further dilution was avoided in order
      to prevent additional mAb modification, and in this way the method was shown to
      be linear from 60 to 5000 mg/L. The precision of the method (repeatability and
      intermediate precision, estimated as the relative standard deviation, RSD %), was
      less than 1.0 %. Accuracy, specificity, robustness, and system suitability were
      also evaluated as specified in the ICH guidelines.We conducted a comprehensive
      chromatographic analysis by submitting RTX to several informative stress
      conditions. These forced degradation studies were conducted for two reasons: to
      estimate the specificity of the method, and to evaluate the robustness of the mAb
      formulation against external stress factors when handling it in preparation for
      administration. Thus, we investigated the effects of acid, base, oxidation, ionic
      strength, temperature, and UV light. Although a slight modification to the intact
      mAb could not be distinguished chromatographically in the stress studies we
      conducted, the procedure proposed here to evaluate peak purity enabled us to
      detect it with a satisfactory level of confidence. The proposed method could
      therefore be considered stability-indicating for quantyfying the intact mAb since
      it is qualified to detect its degradation/modification. Finally, the method was
      used to evaluate RTX in a long-term stability study performed under hospital
      conditions of use.

PMID- 24121432
TI  - An automated headspace solid-phasemicroextraction followed by gas chromatography
      mass spectrometry method to determine macrocyclic musk fragrances in wastewater
      samples.
AB  - A fully automated method has been developed for determining eight macrocyclic
      musk fragrances in wastewater samples. The method is based on headspace solid
      phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry
      (GC-MS). Five different fibres (PDMS 7 MUm, PDMS 30 MUm, PDMS 100 MUm, PDMS/DVB
      65 MUm and PA 85 MUm) were tested. The best conditions were achieved when a
      PDMS/DVB 65 MUm fibre was exposed for 45 min in the headspace of 10 mL water
      samples at 100  degrees C. Method detection limits were found in the low ng L-1
      range between 0.75 and 5 ng L-1 depending on the target analytes. Moreover, under
      optimized conditions, the method gave good levels of intra-day and inter-day
      repeatabilities in wastewater samples with relative standard deviations (n =5,
      1,000 ng L-1) less than 9 and 14 %, respectively. The applicability of the method
      was tested with influent and effluent urban wastewater samples from different
      wastewater treatment plants (WWTPs). The analysis of influent urban wastewater
      revealed the presence of most of the target macrocyclic musks with, most notably,
      the maximum concentration of ambrettolide being obtained in WWTP A (4.36 MUg L-1)
      and WWTP B (12.29 MUg L-1), respectively. The analysis of effluent urban
      wastewater showed a decrease in target analyte concentrations, with exaltone and
      ambrettolide being the most abundant compounds with concentrations varying
      between below method quantification limit (<MQL) and 2.46 MUg L-1.

PMID- 24121433
TI  - Characterizing changes in levan physicochemical properties in different pH
      environments using asymmetric flow field-flow fractionation.
AB  - The purpose of this study was to assess the stability of the polyfructan levan
      under different pH solution conditions by monitoring changes in the levan
      physicochemical properties, such as molar mass (M), root mean square radius
      (r(rms)), hydrodynamic radius (r(h)), structure factor (r(rms)/r(h)), and
      aggregation state with respect to solution pH and hydrolysis time. A commercial
      levan produced from Z. Mobilis was characterized using asymmetric flow field-flow
      fractionation (AF4) in combination with online multiangle light scattering (MALS)
      and differential refractive index (dRI) detection. Under neutral pH solution
      conditions the levan was found to have a M ranging from 10(5) to 5 * 10(7) g/mol,
      a r(rms) ranging from ~25 to 100 nm and a r(h) from ~3 to 151 nm. Two populations
      were observed in the sample. One population with a M less than 106 g/mol which
      represented ~60 % of the sample and a second population with an ultrahigh M up to
      5 * 10(7) g/mol, which comprised ~40 % of the sample. The measured r(rms)/r(h)
      structure factor decreased from 1.8 to 0.65 across the AF4 fractogram indicating
      that early eluting low M levan species had a random coil configuration and late
      eluting high M species had more homogeneous spherical structures. The measured
      apparent density values decreased from 80 to 10 kg/m(3) across the elution
      profile and suggest that the observed second population also contains aggregates.
      The stability of levan in different pH conditions ranging from 1.3 to 8.5 was
      assessed by tracking changes in the average M and r(h), and monitoring the
      formation of fructose over 1 week. The onset of levan acid hydrolysis was
      observed to occur sooner at lower pH conditions and no hydrolysis was observed
      for pH 5.5 and higher.

PMID- 24121434
TI  - A sensitive and selective LC-differential mobility-mass spectrometric analysis of
      allopregnanolone and pregnanolone in human plasma.
AB  - A sensitive and selective method was developed to quantitate allopregnanolone and
      its 5beta isomer pregnanolone in human plasma using liquid chromatography
      differential mobility separation combined with MS/MS detection. The method
      employed a simple liquid-liquid extraction of 100 MUL plasma with hexane/ethyl
      acetate. After extraction, the sample was derivatized using a quaternary aminooxy
      reagent. Separation of allopregnanolone, pregnanolone, and their 3beta epimers
      (epiallopregnanolone and epipregnanolone) was achieved using a Phenomenex Kinetex
      C18 2.1 * 100-mm 2.6-MUm column. A linear calibration curve was obtained over the
      concentration range from 10 to 25,000 pg/mL, and the inter- and intra-day
      accuracy of the quality control samples were between 90 and 110 % with the inter-
      and intra-day precision less than 10 %. The lower limit of quantitation is 50 fg
      (157 amol) on column for both allopregnanolone and pregnanolone which is 100-fold
      less than the underivatized compounds. The recovery is above 95 %, and the
      extracted samples are stable for at least 6 days when stored at 4  degrees C.
      Plasma samples from normal, pregnant, and postpartum women were analyzed using
      this method.

PMID- 24121435
TI  - The structure of the box C/D enzyme reveals regulation of RNA methylation.
AB  - Post-transcriptional modifications are essential to the cell life cycle, as they
      affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D
      ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a
      multitude of guide RNAs as templates for the recognition of rRNA target sites.
      Two methylation guide sequences are combined on each guide RNA, the significance
      of which has remained unclear. Here we use a powerful combination of NMR
      spectroscopy and small-angle neutron scattering to solve the structure of the 390
      kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation
      guide sequences are located in different environments in the complex and that the
      methylation of physiological substrates targeted by the same guide RNA occurs
      sequentially. This structure provides a means for differential control of
      methylation levels at the two sites and at the same time offers an unexpected
      regulatory mechanism for rRNA folding. 

PMID- 24121436
TI  - Genetic identification of a neural circuit that suppresses appetite.
AB  - Appetite suppression occurs after a meal and in conditions when it is
      unfavourable to eat, such as during illness or exposure to toxins. A brain region
      proposed to play a role in appetite suppression is the parabrachial nucleus, a
      heterogeneous population of neurons surrounding the superior cerebellar peduncle
      in the brainstem. The parabrachial nucleus is thought to mediate the suppression
      of appetite induced by the anorectic hormones amylin and cholecystokinin, as well
      as by lithium chloride and lipopolysaccharide, compounds that mimic the effects
      of toxic foods and bacterial infections, respectively. Hyperactivity of the
      parabrachial nucleus is also thought to cause starvation after ablation of
      orexigenic agouti-related peptide neurons in adult mice. However, the identities
      of neurons in the parabrachial nucleus that regulate feeding are unknown, as are
      the functionally relevant downstream projections. Here we identify calcitonin
      gene-related peptide-expressing neurons in the outer external lateral subdivision
      of the parabrachial nucleus that project to the laterocapsular division of the
      central nucleus of the amygdala as forming a functionally important circuit for
      suppressing appetite. Using genetically encoded anatomical, optogenetic and
      pharmacogenetic tools, we demonstrate that activation of these neurons projecting
      to the central nucleus of the amygdala suppresses appetite. In contrast,
      inhibition of these neurons increases food intake in circumstances when mice do
      not normally eat and prevents starvation in adult mice whose agouti-related
      peptide neurons are ablated. Taken together, our data demonstrate that this
      neural circuit from the parabrachial nucleus to the central nucleus of the
      amygdala mediates appetite suppression in conditions when it is unfavourable to
      eat. This neural circuit may provide targets for therapeutic intervention to
      overcome or promote appetite. 

PMID- 24121437
TI  - Effect of natural genetic variation on enhancer selection and function.
AB  - The mechanisms by which genetic variation affects transcription regulation and
      phenotypes at the nucleotide level are incompletely understood. Here we use
      natural genetic variation as an in vivo mutagenesis screen to assess the genome
      wide effects of sequence variation on lineage-determining and signal-specific
      transcription factor binding, epigenomics and transcriptional outcomes in primary
      macrophages from different mouse strains. We find substantial genetic evidence to
      support the concept that lineage-determining transcription factors define
      epigenetic and transcriptomic states by selecting enhancer-like regions in the
      genome in a collaborative fashion and facilitating binding of signal-dependent
      factors. This hierarchical model of transcription factor function suggests that
      limited sets of genomic data for lineage-determining transcription factors and
      informative histone modifications can be used for the prioritization of disease
      associated regulatory variants. 

PMID- 24121438
TI  - Structural basis for modulation of a G-protein-coupled receptor by allosteric
      drugs.
AB  - The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active
      area of modern pharmaceutical research, has proved challenging because neither
      the binding modes nor the molecular mechanisms of such drugs are known. Here we
      determine binding sites, bound conformations and specific drug-receptor
      interactions for several allosteric modulators of the M2 muscarinic acetylcholine
      receptor (M2 receptor), a prototypical family A GPCR, using atomic-level
      simulations in which the modulators spontaneously associate with the receptor.
      Despite substantial structural diversity, all modulators form cation-pi
      interactions with clusters of aromatic residues in the receptor extracellular
      vestibule, approximately 15 A from the classical, 'orthosteric' ligand-binding
      site. We validate the observed modulator binding modes through radioligand
      binding experiments on receptor mutants designed, on the basis of our
      simulations, either to increase or to decrease modulator affinity. Simulations
      also revealed mechanisms that contribute to positive and negative allosteric
      modulation of classical ligand binding, including coupled conformational changes
      of the two binding sites and electrostatic interactions between ligands in these
      sites. These observations enabled the design of chemical modifications that
      substantially alter a modulator's allosteric effects. Our findings thus provide a
      structural basis for the rational design of allosteric modulators targeting
      muscarinic and possibly other GPCRs. 

PMID- 24121439
TI  - Robust twenty-first-century projections of El Nino and related precipitation
      variability.
AB  - The El Nino-Southern Oscillation (ENSO) drives substantial variability in
      rainfall, severe weather, agricultural production, ecosystems and disease in many
      parts of the world. Given that further human-forced changes in the Earth's
      climate system seem inevitable, the possibility exists that the character of ENSO
      and its impacts might change over the coming century. Although this issue has
      been investigated many times during the past 20 years, there is very little
      consensus on future changes in ENSO, apart from an expectation that ENSO will
      continue to be a dominant source of year-to-year variability. Here we show that
      there are in fact robust projected changes in the spatial patterns of year-to
      year ENSO-driven variability in both surface temperature and precipitation. These
      changes are evident in the two most recent generations of climate models, using
      four different scenarios for CO2 and other radiatively active gases. By the mid-
      to late twenty-first century, the projections include an intensification of both
      El-Nino-driven drying in the western Pacific Ocean and rainfall increases in the
      central and eastern equatorial Pacific. Experiments with an Atmospheric General
      Circulation Model reveal that robust projected changes in precipitation anomalies
      during El Nino years are primarily determined by a nonlinear response to surface
      global warming. Uncertain projected changes in the amplitude of ENSO-driven
      surface temperature variability have only a secondary role. Projected changes in
      key characteristics of ENSO are consequently much clearer than previously
      realized. 

PMID- 24121440
TI  - Structural basis for action by diverse antidepressants on biogenic amine
      transporters.
AB  - The biogenic amine transporters (BATs) regulate endogenous neurotransmitter
      concentrations and are targets for a broad range of therapeutic agents including
      selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake
      inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Because eukaryotic BATs
      are recalcitrant to crystallographic analysis, our understanding of the mechanism
      of these inhibitors and antidepressants is limited. LeuT is a bacterial homologue
      of BATs and has proven to be a valuable paradigm for understanding relationships
      between their structure and function. However, because only approximately 25% of
      the amino acid sequence of LeuT is in common with that of BATs, and as LeuT is a
      promiscuous amino acid transporter, it does not recapitulate the pharmacological
      properties of BATs. Indeed, SSRIs and TCAs bind in the extracellular vestibule of
      LeuT and act as non-competitive inhibitors of transport. By contrast, multiple
      studies demonstrate that both TCAs and SSRIs are competitive inhibitors for
      eukaryotic BATs and bind to the primary binding pocket. Here we engineered LeuT
      to harbour human BAT-like pharmacology by mutating key residues around the
      primary binding pocket. The final LeuBAT mutant binds the SSRI sertraline with a
      binding constant of 18 nM and displays high-affinity binding to a range of SSRIs,
      SNRIs and a TCA. We determined 12 crystal structures of LeuBAT in complex with
      four classes of antidepressants. The chemically diverse inhibitors have a
      remarkably similar mode of binding in which they straddle transmembrane helix
      (TM) 3, wedge between TM3/TM8 and TM1/TM6, and lock the transporter in a sodium-
      and chloride-bound outward-facing open conformation. Together, these studies
      define common and simple principles for the action of SSRIs, SNRIs and TCAs on
      BATs. 

PMID- 24121441
TI  - MX2 is an interferon-induced inhibitor of HIV-1 infection.
AB  - HIV-1 replication can be inhibited by type I interferon (IFN), and the expression
      of a number of gene products with anti-HIV-1 activity is induced by type I IFN.
      However, none of the known antiretroviral proteins can account for the ability of
      type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle
      in human cells. Here, by comparing gene expression profiles in cell lines that
      differ in their ability to support the inhibitory action of IFN-alpha at early
      steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as
      an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces
      permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA
      interference reduces the anti-HIV-1 potency of IFN-alpha. HIV-1 reverse
      transcription proceeds normally in MX2-expressing cells, but 2-long terminal
      repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2
      inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with
      this notion, mutations in the HIV-1 capsid protein that are known, or suspected,
      to alter the nuclear import pathways used by HIV-1 confer resistance to MX2,
      whereas preventing cell division increases MX2 potency. Overall, these findings
      indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and
      suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear
      import of subviral complexes. 

PMID- 24121442
TI  - Time resolved observation of the solvation dynamics of a Rydberg excited molecule
      deposited on an argon cluster-I: DABCO* at short times.
AB  - This paper is a joint experimental and theoretical approach concerning a molecule
      deposited on a large argon cluster. The spectroscopy and the dynamics of the
      deposited molecule are measured using the photoelectron spectroscopy. The
      absorption spectrum of the deposited molecule shows two solvation sites populated
      in the ground state. The combined dynamics reveals that the population ratio of
      the two sites is reversed when the molecule is electronically excited. This work
      provides the timescale of the corresponding solvation dynamics. Theoretical
      calculation supports the interpretation. More generally, close examination of the
      short time dynamics (0-6 ps) of DABCO...Ar(n) gives insights into the ultrafast
      relaxation dynamics of molecules deposited at interfaces and provides hence the
      time scale for deposited molecules to adapt to their neighborhoods.

PMID- 24121443
TI  - Insertion of flexible neural probes using rigid stiffeners attached with
      biodissolvable adhesive.
AB  - Microelectrode arrays for neural interface devices that are made of biocompatible
      thin-film polymer are expected to have extended functional lifetime because the
      flexible material may minimize adverse tissue response caused by micromotion.
      However, their flexibility prevents them from being accurately inserted into
      neural tissue. This article demonstrates a method to temporarily attach a
      flexible microelectrode probe to a rigid stiffener using biodissolvable
      polyethylene glycol (PEG) to facilitate precise, surgical insertion of the probe.
      A unique stiffener design allows for uniform distribution of the PEG adhesive
      along the length of the probe. Flip-chip bonding, a common tool used in
      microelectronics packaging, enables accurate and repeatable alignment and
      attachment of the probe to the stiffener. The probe and stiffener are surgically
      implanted together, then the PEG is allowed to dissolve so that the stiffener can
      be extracted leaving the probe in place. Finally, an in vitro test method is used
      to evaluate stiffener extraction in an agarose gel model of brain tissue. This
      approach to implantation has proven particularly advantageous for longer flexible
      probes (>3 mm). It also provides a feasible method to implant dual-sided flexible
      probes. To date, the technique has been used to obtain various in vivo recording
      data from the rat cortex. 

PMID- 24121444
TI  - Monte Carlo dosimetric study of the medium dose rate CSM40 source.
AB  - The (137)Cs medium dose rate (MDR) CSM40 source model (Eckert & Ziegler BEBIG,
      Germany) is in clinical use but no dosimetric dataset has been published. This
      study aims to obtain dosimetric data for the CSM40 source for its use in clinical
      practice as required by the American Association of Physicists in Medicine (AAPM)
      and the European Society for Radiotherapy and Oncology (ESTRO). Penelope2008 and
      Geant4 Monte Carlo codes were used to characterize this source dosimetrically. It
      was located in an unbounded water phantom with composition and mass density as
      recommended by AAPM and ESTRO. Due to the low photon energies of (137)Cs,
      absorbed dose was approximated by collisional kerma. Additional simulations were
      performed to obtain the air-kerma strength, sK. Mass-energy absorption
      coefficients in water and air were consistently derived and used to calculate
      collisional kerma. Results performed with both radiation transport codes showed
      agreement typically within 0.05%. Dose rate constant, radial dose function and
      anisotropy function are provided for the CSM40 and compared with published data
      for other commercially available (137)Cs sources. An uncertainty analysis has
      been performed. The data provided by this study can be used as input data and
      verification in the treatment planning systems. 

PMID- 24121445
TI  - [Karl Jaspers. 100 years of "Allgemeine Psychopathologie" (General
      Psychopathology)].
AB  - With his "Allgemeine Psychopathologie" (general psychopathology) published in
      1913, Karl Jaspers laid a comprehensive methodological and systematic foundation
      in psychiatry. Following Edmund Husserl, the founder of philosophical
      phenomenology, Jaspers introduced "static understanding" into psychopathology,
      i.e. the unprejudiced reproduction of conscious phenomena. From the philosopher
      Wilhelm Dilthey he further adopted the distinction between causal understanding
      as a means of accessing nature and pathological processes and hermeneutic
      understanding, also called genetic understanding, as a way of accessing mental
      phenomena. The intrusion of an event that is incomprehensible in terms of an
      understandable development is seen as indicating an extraconscious phenomenon or
      transition to a somatic process. Jaspers opted for philosophy early in his life.
      After quitting law studies he graduated in medicine, arrived in psychopathology
      without any psychiatric training, to psychology without ever studying psychology
      and to a chair in philosophy without a degree in philosophy. Despite believing
      himself to be chronically ill and to die early, Jaspers produced a life's work
      almost immeasurable in scope. He died in 1969 aged 86 years.

PMID- 24121446
TI  - [The language of the psychiatrist as complementary symbolism.]

PMID- 24121447
TI  - Reactive cognitive-control processes in free-report consonant-vowel dichotic
      listening.
AB  - The relevance of cognitive-control processes has been frequently discussed and
      studied in the context of dichotic listening. Experimental and clinical studies
      indicate that directing attention to either of the two simultaneously presented
      phonological stimuli, but especially to the left-ear stimulus increases the
      requirements for cognitive-control processes. Here, we extend this view by
      reporting the results of a behavioural and a functional magnetic-resonance
      imaging (fMRI) experiment designed to analyse the involvement of cognitive
      control processes also in a free-report dichotic-listening paradigm. It was
      hypothesised that dichotically presented pairs of stop-consonant-vowel syllables
      would provide different demands for cognitive-control processes as a function of
      the spectro-temporal overlap of the two stimuli. Accordingly, in Experiment 1 it
      was shown that dichotic syllables of high (e.g., /ba/ and /ga/) as opposed to low
      spectro-temporal overlap (e.g., /ba/ and /ka/) produce significantly faster and
      more correct answers, and are more often perceived as one syllable. In Experiment
      2 it was further shown that pairs of low as compared to high spectro-temporal
      overlap trigger a more pronounced activation predominately in left-hemispheric,
      speech-associated brain regions, namely left posterior inferior sulcus/gyrus,
      bilaterally in pre-supplementary motor and mid-cingulate cortex as well as in the
      inferior parietal lobe. Taken together, behavioural and functional data indicate
      a stronger involvement of reactive cognitive control in the processing of low
      overlap as opposed to high-overlap stimulus pairs. This supports the notion that
      higher-order, speech-related cognitive-control processes also are involved in a
      free-report dichotic-listening paradigm. 

PMID- 24121448
TI  - Scope of public health measures in ensuring road safety.

PMID- 24121449
TI  - Vodka eyeballing: a potential cause of ocular injuries.

PMID- 24121450
TI  - Lung injury and the cin-namon challenge: college students should beware this
      Internet dare.

PMID- 24121451
TI  - Role of phosphodiesterase inhibitor Ibudilast in morphine-induced hippocampal
      injury.
AB  - BACKGROUND: Opioid drugs are used in the treatment of acute post-surgical pain
      and chronic pain, such as those associated with cancer. Opioid used is associated
      with complications such as analgesic tolerance, dependence and opioid abuse. The
      molecular mechanisms of unwanted opioid responses are varied but recent advances
      have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory
      glial following chronic administration of morphine. In this study we investigated
      the neurodegenerative effects of morphine through its effects on Toll-Like
      Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of
      Interleukin-1 beta (IL-1beta). Then we compared the difference between inhibitory
      effects on mu opioid receptors (by beta-Funaltrexamine, beta-FNA) and TLR4 (by
      Ibudilast). Subsequently, we assessed the amount of IL-1beta and the number of
      granular cells in male rat hippocampus. METHODS: Adult male rats (n=24) were
      treated with sucrose, morphine, Ibudilast (7.5 mg/kg) and beta-FNA (20 mg/kg) for
      30 days. Their brains were isolated and hemisected with one hippocampus for
      granular cell and the other used for IL-1 beta immunoblotting. RESULTS: Data
      showed that Ibudilast suppresses IL-1 beta expression significantly more than
      beta-FNA. The granular cell count displayed significant differences. CONCLUSIONS:
      Our results suggested that Ibudilast can be used for controlling and treatment of
      morphine-induced CNS inflammations or traumatic conditions.

PMID- 24121452
TI  - The impact of environmental factors on traffic accidents in Iran.
AB  - BACKGROUND: Road traffic crashes are the third highest cause of mortality in
      Iran. The aim of this study was to determine the impact of roadway environmental
      factors on traffic crash. METHODS: This cross-sectional study was conducted in
      Iran between March 21, 2010 and December 30, 2010. The data on road traffic
      crashes were obtained from the Traffic Police Department records. These records
      were classified to control for the main confounders related to the type of crash
      and roadway environmental factors. Roadway environmental factors included crash
      scene light, weather, place of accident, the defects and geometrics of roadway
      and road surface. RESULTS: The study included 542,863 traffic crashes. The
      proportions of road traffic crash which led to injury were 24.44% at sunrise and
      27.16% at sunset compared with 5.43% and 1.43% deaths at sunrise and sunset
      respectively. In regard to day time accidents, the proportions were 20.50%
      injuries and 0.55% deaths. The statistical analysis of the results showed that
      the ratio of injuries and deaths were significantly higher at sunrise and sunset
      than those occurring during daytime (P less than 0.001). The highest rate of
      death (5.07%) was due to dusty weather compared to 5.07% for other weather
      conditions (P less than 0.001). The highest mortality rate (3.45%) occurred on
      oily surfaces (P less than 0.001). The defective traffic signs were responsible
      for 30,046 injuries and 5.58% deaths, and road narrowing accounted for 22,775
      injuries and, 4.23% deaths which indicated that the roadway defects inflict most
      frequent injuries and deaths. The lowest (0.74 %) and highest (3.09%) proportion
      of traffic crash- related deaths were due to flat straight and winding
      uphill/downhill roads respectively (P less than 0.001). CONCLUSIONS: Sunrise,
      sunset, dusty weather, oily road surfaces and winding uphill/downhill road were
      hazardous environmental factors. This study provides an insight into the
      potential impacts of environmental factors on road traffic accidents and
      underlines the implementation of appropriate preventive measures.

PMID- 24121453
TI  - Phase 1 study of N(1),N(11)-diethylnorspermine (DENSPM) in patients with advanced
      hepatocellular carcinoma.
AB  - PURPOSE: N(1),N(11)-diethylnorspermine (DENSPM), a synthetic analog of the
      naturally occurring polyamine spermine, can induce polyamine depletion and
      inhibit tumor cell growth. The objectives of this phase I study were to assess
      the safety, maximum-tolerated dose (MTD), pharmacokinetics, and preliminary
      antitumor activity of DENSPM in advanced HCC. METHODS: Patients with measurable
      advanced HCC, Child-Pugh A or B cirrhosis, CLIP score <=3, and Karnofsky score
      >=60 % were eligible. DENSPM was given as a short intravenous infusion on days 1,
      3, 5, 8, 10, and 12 of each 28-day cycle. The starting dose of 30 mg/m(2) was
      escalated at a fixed increment of 15 mg/m(2) until the MTD was identified. The
      plasma pharmacokinetics of DENSPM for the first and last doses given in cycle 1
      was characterized. RESULTS: Thirty-eight patients (male 79 %; median age 61
      years; Child-Pugh A 84 %; >=1 prior systemic therapy 45 %) were enrolled and
      treated. The most common adverse events (AEs) >=grade 1 were fatigue (53 %),
      nausea (34 %), diarrhea (32 %), vomiting (32 %), anemia (29 %), and elevated AST
      (29 %). The most common grade 3-4 AEs were fatigue/asthenia (13 %), elevated AST
      (13 %), hyperbilirubinemia (11 %), renal failure (8 %), and hyperglycemia (8 %).
      The MTD was 75 mg/m(2). There were no objective responses, although 7/38 (18 %)
      patients achieved stable disease for >=16 weeks. The overall mean (+/-SD) total
      body clearance for the initial dose, 66.3 +/- 35.9 L/h/m(2) (n = 16), was
      comparable to the clearance in patients with normal to near normal hepatic
      function. Drug levels in plasma decayed rapidly immediately after the infusion
      but remained above 10 nM for several days after dosing at the MTD. CONCLUSIONS:
      N(1),N(11)-diethylnorspermine treatment at the MTD of 75 mg/m(2), given
      intravenously every other weekday for two consecutive weeks of each 28-day cycle,
      was relatively well tolerated in patients with advanced HCC including those with
      mild-to-moderate liver dysfunction. This administration schedule provided
      prolonged systemic exposure to potentially effective concentrations of the drug.
      Stable disease was seen in 18 % of patients receiving DENSPM treatment. Further
      evaluation of DENSPM monotherapy for advanced HCC does not appear to be justified
      because of insufficient evidence of clinical benefit in the patients evaluated in
      this study.

PMID- 24121454
TI  - Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2,
      multicenter, randomized, double-blind, placebo-controlled trial of goshajinkigan
      to prevent oxaliplatin-induced neuropathy.
AB  - PURPOSE: Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and
      potentially severe, but successful treatment of this condition is still an unmet
      clinical need. We aimed to determine whether treatment with goshajinkigan (TJ
      107), a traditional Japanese medicine, is better than placebo in preventing OPN
      in patients with advanced or recurrent colorectal cancer patients treated with
      standard FOLFOX regimens. METHODS: In this phase 2, randomized, double-blind,
      placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were
      randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The
      severity of OPN was assessed according to the Common Toxicity Criteria for
      Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks
      thereafter until the 26th week. The primary endpoint was the incidence of grade 2
      or greater OPN until the 8th cycle of chemotherapy. RESULTS: Analyses were done
      by intention to treat. Eighty-nine patients were randomly assigned to receive
      either TJ-107 (n = 44) or placebo (n = 45) between May 2009 and March 2010. The
      incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ
      107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47
      1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51,
      0.14-1.92). No concerns regarding toxicity emerged with TJ-107 treatment.
      CONCLUSIONS: TJ-107 appears to have an acceptable safety margin and a promising
      effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX
      efficacy.

PMID- 24121455
TI  - Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer
      harboring epidermal growth factor receptor mutations: additive analysis of
      pharmacokinetics.
AB  - BACKGROUND: We conducted a phase II trial of erlotinib in patients with advanced
      non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor
      (EGFR) mutations and evaluated the relationship between plasma concentration and
      efficacy of erlotinib. METHODS: Patients who were previously treated but naive to
      epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with
      advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at
      150 mg once daily until disease progression. The primary end point was objective
      response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2
      (D2) and 8 (D8) by high-performance liquid chromatography. RESULTS: In total, 29
      patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 %
      confidence interval [CI] 40.57-79.8) of 26 assessable patients. The median
      progression-free survival (PFS) and overall survival (OS) were 6.3 months and
      16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade
      1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood
      samples from 16 patients. The median PFS of the high and low D8/D2 ratio group
      was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95
      % CI 0.094-0.968). CONCLUSION: Erlotinib showed an ORR comparable to that seen in
      previous studies for patients with NSCLC harboring EGFR mutations, although
      response, the primary end point, did not reach the predetermined threshold level.
      The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor
      for PFS.

PMID- 24121457
TI  - Enantioselective total synthesis of macrolide (+)-neopeltolide.
AB  - The asymmetric total synthesis of the anti-proliferative macrolide (+)
      neopeltolide has been completed. The stereochemically defined trisubstituted
      tetrahydropyran ring was constructed via a catalytic hetero-Diels-Alder reaction
      creating two new chiral centers in a highly diastereoselective manner. The other
      key features of this synthesis included Brown's asymmetric allylation to install
      the requisite C-11 and C-13 stereocenters. The synthesis of the oxazole side
      chain consisted of a hydrozirconation of an alkynyl stannane to establish the Z
      stereochemistry, followed by a palladium catalyzed cross coupling to introduce
      the desired Z olefin in the oxazole side chain. 

PMID- 24121456
TI  - A retrospective analysis of early CA19-9 change in salvage chemotherapy for
      refractory pancreatic cancer.
AB  - PURPOSE: In salvage chemotherapy for refractory pancreatic cancer, early
      assessment is important to avoid unnecessary toxicities from ineffective
      chemotherapy. Early CA19-9 change after the first course as a prognostic factor
      was evaluated in this setting. METHODS: Patients receiving salvage chemotherapy
      were retrospectively studied. CA19-9 was measured prior to and after the first
      course. Cox regression analysis was performed for prognostic factors for
      progression-free survival (PFS) and overall survival (OS), using the landmark
      method defined as a day of CA19-9 measurement after the first course. RESULTS: A
      total of 239 salvage regimens were given in 167 patients. Median PFS and OS were
      2.7 and 6.1 months, respectively. Median pretreatment CA19-9 was 2,362 U/mL, and
      median CA19-9 change after the first course was 17.8 % increase. CA19-9 change
      was associated with tumor response, and PFS was 1.7 versus 3.5 months and OS was
      3.9 and 8.6 months in patients with >=50 % versus <50 % increase. In the
      multivariate analyses, CA19-9 increase >=50 % was prognostic of both PFS and OS
      (HR 2.28 and 2.50, p < 0.001, respectively). CONCLUSION: CA19-9 change after the
      first course was prognostic of PFS and OS in refractory pancreatic cancer. Early
      discontinuation should be considered given the palliative setting.

PMID- 24121458
TI  - Expanding the scope of oxime ligation: facile synthesis of large cyclopeptide
      based glycodendrimers.
AB  - A new series of 64-valent glycodendrimers was prepared in excellent yield and
      purity using a divergent and iterative strategy based on oxime ligation. Enzyme
      linked lectin assays revealed the first nanomolar inhibitor for the fucose
      specific lectin isolated from Ulex europaeus. 

PMID- 24121459
TI  - Network-based analysis of omics with multi-objective optimization.
AB  - Nowadays, computational and statistical methods focusing on integrated analysis
      of omics data are necessary. A few approaches have been recently described in the
      literature and a small number of software packages are available. We have
      developed a new method to generate networks of biological components that
      incorporate multi-omics information. The novelty of this method relies on using a
      multi-objective (MO) optimization procedure in order to drive the identification
      of networks that are enriched according to several statistical estimators. The
      network-based analysis of omics with MO optimization described in this work can
      be applied to different types of omics and biological interactions. By using this
      approach we found protein networks that participate in the establishment of the
      increased basal differentiation observed in breast tumors of BRCA1-mutation
      carriers. Additionally, we showed how MO optimization can be used to carry out a
      network-based comparison among several omic data sets: using transcriptomic data
      from two types of breast tumors and the corresponding epithelial cells from which
      tumors were generated, we found a protein network that shows a strong and
      coherent (the same direction) differential expression when comparing each tumor
      with its respective epithelial tissue. We have also compared the transcriptional
      variation detected in three different types of tumors originated in breast, colon
      and pancreas with the corresponding healthy tissues. Despite the global low
      correlation observed in the three pairs of tumors, we found more similar networks
      regulated in the same direction in colon and pancreas tumor cells. In conclusion,
      we propose the network-based analysis of omics with MO optimization as a valid
      tool for integrated analysis of omics data. 

PMID- 24121460
TI  - Synthesis and structure of N,C-chelated organoantimony(v) and organobismuth(v)
      compounds.
AB  - The reaction of N,C-intramolecularly coordinated organoantimony(iii) and
      organobismuth(iii) compounds LMCl2 (M = Sb () or Bi () and L = [o-(CH[double
      bond, length as m-dash]N-2,6-iPr2C6H3)C6H4]) with phenyllithium in a 1 : 1 or 1 :
      2 molar ratio gave compounds LM(Ph)Cl (M = Sb () or Bi ()) and LMPh2 (M = Sb ()
      or Bi ()) in moderate to good yields. Compound could also be prepared by the
      treatment of the lithium compound LLi with in situ prepared PhSbCl2. Oxidation of
      the antimony(iii) compounds , and with one equivalent of SO2Cl2 proceeded
      smoothly with formation of organoantimony(v) compounds LSbCl4 (), LSb(Ph)Cl3 ()
      and LSbPh2Cl2 () in nearly quantitative yields. Compounds are yellowish solids
      that are stable for a long time even in the presence of air. In contrast, only
      organobismuth(iii) compounds and could be successfully oxidized using SO2Cl2 to
      give compounds LBi(Ph)Cl3 () and LBiPh2Cl2 (). Compound is stable, but compound
      readily decomposed in solution and could not be isolated and stored for a longer
      period. All attempts to prepare compound LBiCl4 by the oxidation of with SO2Cl2
      failed and resulted only in a mixture of products. All studied compounds were
      characterized by electrospray ionization (ESI) mass spectrometry, and (1)H and
      (13)C NMR spectroscopy. The molecular structures of , and were unambiguously
      established using single-crystal X-ray diffraction analysis. 

PMID- 24121461
TI  - Sustained PKCbetaII activity confers oncogenic properties in a phospholipase D-
      and mTOR-dependent manner.
AB  - Protein kinase C (PKC) is a family of serine/threonine kinases implicated in a
      variety of physiological processes. We have shown previously that sustained
      activation of the classical PKCalpha and PKCbetaII induces their phospholipase D
      (PLD)-dependent internalization and translocation to a subset of the recycling
      endosomes defined by the presence of PKC and PLD (the pericentrion), which
      results in significant differences in phosphorylation of PKC substrates. Here, we
      have investigated the biological consequences of sustained PKC activity and the
      involvement of PLD in this process. We find that sustained activation of PKC
      results in activation of the mammalian target of rapamycin (mTOR)/S6 kinase
      pathway in a PLD- and endocytosis-dependent manner, with both pharmacologic
      inhibitors and siRNA implicating the PLD2 isoform. Notably, dysregulated
      overexpression of PKCbetaII in A549 lung cancer cells was necessary for the
      enhanced proliferation and migration of these cancer cells. Inhibition of
      PKCbetaII with enzastaurin reduced A549 cell proliferation by >60% (48 h) and
      migration by >50%. These biological effects also required both PLD activity and
      mTOR function, with both the PLD inhibitor FIPI and rapamycin reducing cell
      growth by >50%. Reciprocally, forced overexpression of wild-type PKCbetaII, but
      not an F666D mutant that cannot interact with PLD, was sufficient to enhance cell
      growth and increase migration of noncancerous HEK cells; indeed, both properties
      were almost doubled when compared to vector control and PKC-F666D-overexpressing
      cells. Notably, this condition was also dependent on both PLD and mTOR activity.
      In summary, these data define a PKC-driven oncogenic signaling pathway that
      requires both PLD and mTOR, and suggest that inhibitors of PLD or mTOR would be
      beneficial in cancers where PKC overexpression is a contributing or driving
      factor.

PMID- 24121462
TI  - Control of spasticity in a multiple sclerosis model using central nervous system
      excluded CB1 cannabinoid receptor agonists.
AB  - The purpose of this study was the generation of central nervous system (CNS)
      excluded cannabinoid receptor agonists to test the hypothesis that inhibition of
      spasticity, due to CNS autoimmunity, could be controlled by affecting
      neurotransmission within the periphery. Procedures included identification of
      chemicals and modeling to predict the mode of exclusion; induction and control of
      spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of
      CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the
      mechanism of CNS-exclusion via drug pumps; genome-wide association study in
      N2(129*ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing
      and detection of cannabinoid drug-pump activity in human brain endothelial cell
      lines. Three drugs (CT3, SAB378 and SAD448) were identified that control
      spasticity via action on the peripheral nerve CB1 receptor. These were
      peripherally restricted via drug pumps that limit the CNS side effects
      (hypothermia) of cannabinoids to increase the therapeutic window. A cannabinoid
      drug pump is polymorphic and functionally lacking in many laboratory (C57BL/6,
      129, CD-1) mice used for transgenesis, pharmacology, and toxicology studies. This
      phenotype was mapped and controlled by 1-3 genetic loci. ABCC1 within a cluster
      showing linkage is a cannabinoid CNS-drug pump. Global and conditional CB1
      receptor-knockout mice were used as controls. In summary, CNS-excluded CB1
      receptor agonists are a novel class of therapeutic agent for spasticity.

PMID- 24121463
TI  - The boundary of the meristematic and elongation zones in roots: endoreduplication
      precedes rapid cell expansion.
AB  - Plant roots consist of a meristematic zone of mitotic cells and an elongation
      zone of rapidly expanding cells, in which DNA replication often occurs without
      cell division, a process known as endoreduplication. The duration of the cell
      cycle and DNA replication, as measured by 5-ethynyl-2'-deoxy-uridine (EdU)
      incorporation, differed between the two regions (17 h in the meristematic zone,
      30 h in the elongation zone). Two distinct subnuclear patterns of EdU signals,
      whole and speckled, marked nuclei undergoing DNA replication at early and late S
      phase, respectively. The boundary region between the meristematic and elongation
      zones was analysed by a combination of DNA replication imaging and optical
      estimation of the amount of DNA in each nucleus (C-value). We found a boundary
      cell with 4C nuclei exhibiting the whole pattern of EdU signals. Analyses of
      cells in the boundary region revealed that endoreduplication precedes rapid cell
      elongation in roots.

PMID- 24121464
TI  - Barriers and facilitators to implementing delirium rounds in a clinical trial
      across three diverse hospital settings.
AB  - Delirium occurs in more than half of hospitalized older adults with dementia,
      substantially worsening outcomes. The use of multiple strategies and a local
      opinion leader, unit champion, has cumulative and lasting effects compared with
      single-strategy interventions. The purpose of this article is to describe the
      early barriers and facilitators to rounding with unit champions in a cluster
      randomized clinical trial in Year 2 of a 5-year trial (5R01NR011042-02). This is
      a mixed-method study nested within an ongoing multisite cluster-randomized,
      controlled clinical trial. Descriptive and comparative statistics were collected
      on N = 192 nursing rounds. Qualitative data were thematically analyzed. On
      average, rounds lasted 25.54 min (SD = 13.18) and were conducted with the unit
      champion 64% of the time. This is one of the first studies to systematically
      address quantitative and qualitative barriers and facilitators to nurse-led
      delirium rounds, demonstrating the gradual adoption of an intervention in diverse
      clinical settings. 

PMID- 24121465
TI  - The relationship between personal unsecured debt and mental and physical health:
      a systematic review and meta-analysis.
AB  - This paper systematically reviews the relationship between personal unsecured
      debt and health. Psychinfo, Embase and Medline were searched and 52 papers were
      accepted. A hand and cited-by search produced an additional 13 references leading
      to 65 papers in total. Panel surveys, nationally representative epidemiological
      surveys and psychological autopsy studies have examined the relationship, as have
      studies on specific populations such as university students, debt management
      clients and older adults. Most studies examined relationships with mental health
      and depression in particular. Studies of physical health have also shown a
      relationship with self-rated health and outcomes such as obesity. There is also a
      strong relationship with suicide completion, and relationships with drug and
      alcohol abuse. The majority of studies found that more severe debt is related to
      worse health; however causality is hard to establish. A meta-analysis of pooled
      odds ratios showed a significant relationship between debt and mental disorder
      (OR=3.24), depression (OR=2.77), suicide completion (OR=7.9), suicide completion
      or attempt (OR=5.76), problem drinking (OR=2.68), drug dependence (OR=8.57),
      neurotic disorder (OR=3.21) and psychotic disorders (OR=4.03). There was no
      significant relationship with smoking (OR=1.35, p>.05). Future longitudinal
      research is needed to determine causality and establish potential mechanisms and
      mediators of the relationship. 

PMID- 24121466
TI  - Secretion of adiponectin from mouse aorta and its role in cold storage-induced
      vascular dysfunction.
AB  - Availability of adiponectin plays a crucial role in cardiovascular function. The
      present study was conducted to evaluate the presence, alterations and impact of
      the various adiponectin isoforms in vascular tissue under clinically relevant in
      vitro conditions (cold storage). Presence of various adiponectin isoforms in
      vascular smooth muscle cells and their regulation during cold storage was
      evaluated by PCR, western blot, ELISA and immunohistochemistry. The impact of the
      various isoforms for vessel preservation was assessed using isometric force
      measurement as an in vitro assay for vascular function. Adiponectin is expressed
      in smooth muscle cells from murine aortae and human saphenous veins. Following 2
      days of cold storage adiponectin mRNA expression in mouse aorta is reduced, which
      appears to be regulated indirectly by miR-292-3p. Despite the reduced mRNA
      expression, adiponectin accumulated in cold storage supernatant over 2 days
      indicating a net release of adiponectin. Two days of cold storage resulted in an
      impairment of endothelium-dependent relaxation which was prevented by addition of
      full-length adiponectin in concentrations similar to normal plasma levels during
      storage. In contrast, addition of recombinant adiponectin which is unable to form
      high order multimers failed to improve vessel function. High concentrations (20
      MUg/mL) of this trimeric isoform even reduced the vasorelaxation response and
      facilitated uncoupling of endothelial nitric oxide synthase. Endothelial injury
      by cold storage may partly be prevented by addition of high-molecular-weight
      adiponectin. This effect may support graft patency to avoid coagulation- and
      atherosclerosis-associated impairment of perfusion.

PMID- 24121468
TI  - Identification and characterization of individual airborne volcanic ash particles
      by Raman microspectroscopy.
AB  - We present for the first time the Raman microspectroscopic identification and
      characterization of individual airborne volcanic ash (VA) particles. The
      particles were collected in April/May 2010 during research aircraft flights,
      which were performed by Deutsches Zentrum fur Luft- und Raumfahrt in the airspace
      near the Eyjafjallajokull volcano eruption and over Europe (between Iceland and
      Southern Germany). In addition, aerosol particles were sampled by an Electrical
      Low Pressure Impactor in Munich, Germany. As references for the Raman analysis,
      we used the spectra of VA collected at the ground near the place of eruption, of
      mineral basaltic rock, and of different minerals from a database. We found
      significant differences in the spectra of VA and other aerosol particles (e.g.,
      soot, nitrates, sulfates, and clay minerals), which allowed us to identify VA
      among other atmospheric particulate matter. Furthermore, while the airborne VA
      shows a characteristic Raman pattern (with broad band from ca. 200 to ca. 700 cm(
      1) typical for SiO2 glasses and additional bands of ferric minerals), the
      differences between the spectra of aged and fresh particles were observed,
      suggesting differences in their chemical composition and/or structure. We also
      analyzed similarities between Eyjafjallajokull VA particles collected at
      different sampling sites and compared the particles with a large variety of
      glassy and crystalline minerals. This was done by applying cluster analysis, in
      order to get information on the composition and structure of volcanic ash.

PMID- 24121469
TI  - In vitro synthesis and characterisation of three fenoterol sulfoconjugates
      detected in fenoterol post-administration urine samples.
AB  - Fenoterol, a fast-acting beta2-adrenergic agonist, is used in the therapy of
      obstructive pulmonary diseases and for the inhibition of premature labour
      obstetrics. Doping control for beta2-agonists, which are prohibited in sports by
      the World Anti-Doping Agency, is commonly performed by liquid chromatography/mass
      spectrometry after hydrolysis of phase II metabolites. The continuing development
      of analytical procedures has led to direct injection of urine samples without
      sample preparation becoming a viable tool. For the detection of substances
      without sample preparation, including hydrolysis, detailed information of the
      phase II metabolism of the substances is essential. In this study, human S9
      fractions of different tissues and two recombinant sulfotransferases were
      investigated for their potential to form fenoterol sulfoconjugates, which were
      characterised in detail. Two mono-sulfoconjugates and one bis-sulfoconjugate were
      synthesised and their structures confirmed by liquid chromatography-high
      resolution/high-accuracy mass spectrometry. All of the metabolites were
      identified as esterified phenolic compounds. Excretion studies with orally and
      inhalatively administered fenoterol proved the occurrence of the sulfoconjugates
      in vivo. Inhalatively administered fenoterol resulted in the detection of the two
      monosulfoconjugates in low amounts in urine due to the lower inhalation dose of
      fenoterol compared to the oral dose. After oral uptake of fenoterol, the two mono
      sulfoconjugates and a fenoterol bis-sulfoconjugate were detected in urine. This
      is the first report of the bis-sulfoconjugate.

PMID- 24121467
TI  - Healthcare disparities in critical illness.
AB  - OBJECTIVE: To summarize the current literature on racial and gender disparities
      in critical care and the mechanisms underlying these disparities in the course of
      acute critical illness. DATA SOURCES: MEDLINE search on the published literature
      addressing racial, ethnic, or gender disparities in acute critical illness, such
      as sepsis, acute lung injury, pneumonia, venous thromboembolism, and cardiac
      arrest. STUDY SELECTION: Clinical studies that evaluated general critically ill
      patient populations in the United States as well as specific critical care
      conditions were reviewed with a focus on studies evaluating factors and
      contributors to health disparities. DATA EXTRACTION: Study findings are presented
      according to their association with the prevalence, clinical presentation,
      management, and outcomes in acute critical illness. DATA SYNTHESIS: This review
      presents potential contributors for racial and gender disparities related to
      genetic susceptibility, comorbidities, preventive health services, socioeconomic
      factors, cultural differences, and access to care. The data are organized along
      the course of acute critical illness. CONCLUSIONS: The literature to date shows
      that disparities in critical care are most likely multifactorial involving
      individual, community, and hospital-level factors at several points in the
      continuum of acute critical illness. The data presented identify potential
      targets as interventions to reduce disparities in critical care and future
      avenues for research.

PMID- 24121471
TI  - Electrochemical assay of the relationship between the inhibition of
      phosphatidylinositol 3-kinase pathway and estrogen receptor expression in breast
      cancer.
AB  - Breast cancer has become one of the most threatening diseases to women throughout
      the world. Emerging evidence implies that estrogen receptor (ER) and
      phosphatidylinositol 3-kinase (PI3K) pathways play central roles in both breast
      cancer progression and response to therapy. In this work, we have probed into ER
      expression related to the PI3K pathway at the protein level with an
      electrochemical technique based on the detection of ER proteins in nuclear
      extracts with an Exonuclease III protection-based strategy. Experimental results
      show that an increased number of ER proteins can be detected upon PI3K
      inhibition, demonstrating the reversal effect of the PI3K inhibitor on ER
      expression. Moreover, treatment with different concentrations of the PI3K
      inhibitor NVP-BEZ235 can result in a dose-dependent alteration of ER protein
      levels, implying an intimate link between ER and PI3K pathways. This work may be
      a great help to understand the mysteries underlying PI3K-related endocrine
      resistance and to evaluate the effect of therapeutic interventions in the future.

PMID- 24121470
TI  - DMSO-enhanced MALDI MS imaging with normalization against a deuterated standard
      for relative quantification of dasatinib in serial mouse pharmacology studies.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry imaging is an
      emerging powerful technique in drug metabolism and pharmacokinetics research.
      Despite recent progress in mass-spectrometry-based localization and relative
      quantification of small-molecule drugs and their metabolites in tissue, improved
      methods for drug extraction/ionization are required. Furthermore, relative
      quantification of drugs by mass spectrometry imaging in larger rodent cohorts is
      a necessary proof-of-concept study to demonstrate the utility of such a workflow
      in an industrial setting. Using as an example the tyrosine kinase inhibitor
      dasatinib, a leukemia drug, we demonstrate that inclusion of dimethyl sulfoxide
      in standard matrix solutions significantly improves ion intensity in mass
      spectrometry images and reveals enrichment of the drug in mouse kidney medulla.
      We furthermore show in a time-course study in multiple mice that normalization
      against a deuterated internal standard, dasatinib-D8, which is applied together
      with the matrix, makes possible relative quantification of the drug that
      correlates well with canonical liquid chromatography-tandem mass spectrometry
      based drug quantification.

PMID- 24121472
TI  - The effect of fluorine substitution on chiral recognition: interplay of CH...pi,
      OH...pi and CH...F interactions in gas-phase complexes of 1-aryl-1-ethanol with
      butan-2-ol.
AB  - The molecular diastereomeric complexes between R-1-phenyl-1-ethanol, S-1-(4
      fluorophenyl)ethanol and S-1-(2-fluorophenyl)ethanol and R and S-butan-2-ol,
      isolated under molecular beam conditions in the gas phase, have been investigated
      by mass-selective resonant two-photon ionization (R2PI) and infrared depleted
      R2PI (IR-R2PI). The comparison of the three systems allowed us to highlight the
      significance of specific intermolecular interactions in the chiral discrimination
      process. The interpretation of the results is based on theoretical predictions
      mainly at the D-B3LYP/6-31++G** level of theory. The homo and heterochiral
      complexes are endowed with fine differences in intermolecular interactions,
      namely strong OH...O, and weaker CH...pi, OH...pi, CH...F as well as repulsive
      interactions. The presence of a fluorine atom in the para position of the
      aromatic ring does not influence the overall geometry of the complex whilst it
      affects the electron density in the pi system and the strength of CH...pi and
      OH...pi interactions. The role and the importance of CH...F intermolecular
      interactions are evident in the complexes with fluorine substitution in the ortho
      position. While the ortho hetero complex is structurally analogous to the hetero
      para and non-fluorinated structures, butan-2-ol in the ortho homo adduct adopts a
      different conformation in order to establish a CH...F intermolecular interaction.

PMID- 24121473
TI  - [Systemic therapy of metastatic bladder cancer.]
AB  - This review focuses on current options in the medical therapy of metastasized
      urothelial carcinoma of the bladder. Standard treatments as well as new, recently
      published therapeutic approaches are evaluated and discussed.

PMID- 24121474
TI  - [ASA and clopidogrel for urological operations. Perioperative management].
AB  - In a systematic overview and meta-analysis among more than 50,000 patients at
      risk for coronary artery disease, not adhering to or discontinuing aspirin
      (acetylsalicylic acid, ASA) was associated with a significantly increased risk of
      non-fatal myocardial infarction or death. Withdrawal of low dose aspirin was
      correlated with a threefold increase in the risk of adverse cardiovascular
      events. This risk is present irrespective of the length of time patients had been
      taking low dose aspirin. Therefore, in patients on chronic low dose aspirin for
      secondary prevention of cardiovascular disease, aspirin should never be
      discontinued. In the few available studies in urological surgery the increase in
      bleeding does not translate into a significant increase in specific morbidity.
      This seems to be also true for the additional administration of clopidogrel to
      aspirin. Nevertheless, in patients with drug-eluting stents and dual antiplatelet
      therapy, urologists should ensure a multidisciplinary management of the
      perioperative course.

PMID- 24121475
TI  - Selective inversion of 1H resonances in solid-state nuclear magnetic resonance:
      Use of double-DANTE pulse sequence.
AB  - We here present a method based on DANTE pulses and homonuclear dipolar decoupling
      scheme to invert selectively any desired resonance in a proton spin system under
      magic-angle spinning. Experimental results are reported on a sample of L
      histidine.HCl.H2O at magic-angle spinning frequencies of 15 and 60kHz. The
      results are also substantiated numerically. 

PMID- 24121476
TI  - HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting.
AB  - HSPA8/HSC70 protein is a fascinating chaperone protein. It represents a
      constitutively expressed, cognate protein of the HSP70 family, which is central
      in many cellular processes. In particular, its regulatory role in autophagy is
      decisive. We focused this review on HSC70 structure-function considerations and
      based on this, we put a particular emphasis on HSC70 targeting by small molecules
      and peptides in order to develop intervention strategies that deviate some of
      HSC70 properties for therapeutic purposes. Generating active biomolecules
      regulating autophagy via its effect on HSC70 can effectively be designed only if
      we understand the fine relationships between HSC70 structure and functions. 

PMID- 24121477
TI  - Large-scale gene knockdown in C. elegans using dsRNA feeding libraries to
      generate robust loss-of-function phenotypes.
AB  - RNA interference by feeding worms bacteria expressing dsRNAs has been a useful
      tool to assess gene function in C. elegans. While this strategy works well when a
      small number of genes are targeted for knockdown, large scale feeding screens
      show variable knockdown efficiencies, which limits their utility. We have
      deconstructed previously published RNAi knockdown protocols and found that the
      primary source of the reduced knockdown can be attributed to the loss of dsRNA
      encoding plasmids from the bacteria fed to the animals. Based on these
      observations, we have developed a dsRNA feeding protocol that greatly reduces or
      eliminates plasmid loss to achieve efficient, high throughput knockdown. We
      demonstrate that this protocol will produce robust, reproducible knock down of C.
      elegans genes in multiple tissue types, including neurons, and will permit
      efficient knockdown in large scale screens. This protocol uses a commercially
      available dsRNA feeding library and describes all steps needed to duplicate the
      library and perform dsRNA screens. The protocol does not require the use of any
      sophisticated equipment, and can therefore be performed by any C. elegans lab. 

PMID- 24121478
TI  - Flow cytometric chemosensitivity assay using JC-1, a sensor of mitochondrial
      transmembrane potential, in acute leukemia.
AB  - PURPOSE: The purpose of the study is to establish a simple and relatively
      inexpensive flow cytometric chemosensitivity assay (FCCA) for leukemia to
      distinguish leukemic blasts from normal leukocytes in clinical samples. METHODS:
      We first examined whether the FCCA with the mitochondrial membrane depolarization
      sensor, 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethyl benzimidazolo
      carbocyanine iodide (JC-1), could detect drug-induced apoptosis as the
      conventional FCCA by annexin V/7-AAD detection did and whether it was applicable
      in the clinical samples. Second, we compared the results of the FCCA for
      prednisolone (PSL) with clinical PSL response in 18 acute lymphoblastic leukemia
      (ALL) patients to evaluate the reliability of the JC-1 FCCA. Finally, we
      performed the JC-1 FCCA for bortezomib (Bor) in 25 ALL or 11 acute myeloid
      leukemia (AML) samples as the example of the clinical application of the FCCA.
      RESULTS: In ALL cells, the results of the JC-1 FCCA for nine anticancer drugs
      were well correlated with those of the conventional FCCA using anti-annexin V
      antibody (P < 0.001). In the clinical samples from 18 children with ALL, the
      results of the JC-1 FCCA for PSL were significantly correlated with the clinical
      PSL response (P = 0.005). In ALL samples, the sensitivity for Bor was found to be
      significantly correlated with the sensitivity for PSL (P = 0.005). In AML
      samples, the Bor sensitivity was strongly correlated with the cytarabine
      sensitivity (P = 0.0003). CONCLUSIONS: This study showed the reliability of a
      relatively simple and the FCCA using JC-1, and the possibility for the further
      clinical application.

PMID- 24121479
TI  - A novel antitumor piperazine alkyl compound causes apoptosis by inducing RhoB
      expression via ROS-mediated c-Abl/p38 MAPK signaling.
AB  - PURPOSE: We investigated the action mechanism of a novel anticancer compound,
      KR28 (1-allyl-4-dodecanoyl-1-ethyl-piperazin-1-ium; bromide), to induce apoptosis
      of human prostate carcinoma PC-3 cells. METHODS: To explore an apoptotic
      signaling of KR28, we used ROS assay, SRB assay, flow cytometry analysis,
      reporter assay, xenograft assay, Western blotting, and RT-PCR analysis. RESULTS:
      The growth inhibitory action of KR28 is cell line specific, impeding the growth
      of prostate carcinoma PC-3 and stomach carcinoma NUGC-3 cells. KR28 showed strong
      antitumor activity in PC-3 mouse xenograft model. KR28 increased ROS production,
      leading to nuclear c-Abl expression, which in turn activated p38 mitogen
      activated protein kinase (MAPK) to enhance the expression of RhoB, an apoptosis
      inducer. The KR28-induced apoptosis was abrogated by the ROS scavenger N
      acetylcysteine and by knockdown of c-Abl, p38 MAPK, or ATF2. Moreover, the p300
      binding site and two CCAAT boxes in the RhoB promoter appear to be involved in
      ROS-mediated RhoB expression in the presence of KR28. CONCLUSION: The antitumor
      agent KR28 induces apoptosis of PC-3 cells by ROS-mediated RhoB expression via c
      Abl upregulation and activation of p38 MAPK/ATF-2.

PMID- 24121480
TI  - Evaluation of safety parameters and changes in serum concentration in liver
      transplant recipients treated with doxorubicin during the anhepatic period.
AB  - PURPOSE: Because of the recurrence of hepatocellular carcinoma (HCC) at the graft
      after liver transplantation, circulating HCC cells may be present during the
      anhepatic period. Intravenous doxorubicin (DOX) is used during the anhepatic
      period to combat these cells; however, pharmacokinetics data have been poorly
      analyzed. This study aims to investigate DOX administration during the anhepatic
      period. PATIENTS AND METHODS: We administered 5 mg/m(2) DOX immediately after
      liver removal and compared serum DOX concentrations at several intervals during
      the anhepatic period in patients who underwent liver transplantation because of
      liver cirrhosis and HCC (n = 3) and patients who underwent liver resection owing
      to HCC with portal vein tumor thrombi (n = 5). We also measured serum DOX
      concentrations and pharmacokinetic parameters in transplant patients that
      received 3-15 mg/m(2) DOX (n = 3 per dose level). We evaluated transplant
      patients' adverse drug reactions and survival. RESULTS: At 10 and 30 min after
      DOX administration, serum DOX concentrations were elevated two- to threefold in
      transplant patients versus resection patients. Dose escalation in transplant
      patients exhibited a prolonged T1/2 in the one-compartment model and T1/2 beta in
      the two-compartment model, as well as a dose-dependent elevation of the area
      under the curve. No obvious adverse drug reactions were noted at 3-15 mg/m(2)
      DOX. In transplant patients, 5-year recurrence-free survival was 68.8 %; overall
      survival was 100.0 %. CONCLUSION: During the anhepatic period, serum DOX
      concentrations were elevated two- to threefold, T1/2 was prolonged dose
      dependently, and up to 15 mg/m(2) DOX could be safely administered

PMID- 24121481
TI  - Tuning the olefin epoxidation by manganese(III) complexes of bisphenolate
      ligands: effect of Lewis basicity of ligands on reactivity.
AB  - A new family of manganese(iii) complexes of the type [Mn(L)Cl], where H2L is 1,4
      bis(2-hydroxy-benzyl)-1,4-diazepane (), 1,4-bis(2-hydroxy-4-methylbenzyl)-1,4
      diazepane (), 1,4-bis(2-hydroxy-3,5-dimethylbenzyl)-1,4-diazepane () and 1,4
      bis(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diazepane (), has been isolated and
      studied as a catalyst for epoxidation reaction. Complexes have been characterized
      using elemental analysis, electronic spectral and electrochemical methods and ESI
      MS. The single crystal X-ray structures of and contain the MnN2O2Cl chromophore
      with a novel square pyramidal coordination geometry (tau: , 0.11; , 0.00). All
      the complexes possess a distorted square pyramidal coordination geometry in
      solution, as revealed by the characteristic bands observed in the electronic
      spectra. A time dependent density functional theory (TD-DFT) calculation has been
      performed to assist in the assignment of the electronic absorption spectral bands
      of the complexes. The Mn(iii)/Mn(ii) redox potentials (E1/2) of fall within the
      narrow range of 0.279-0.320 V. The catalytic ability of the complexes towards
      olefin epoxidation has been investigated using PhIO as the oxygen source at room
      temperature under an N2 atmosphere. Addition of N-methylimidazole to the reaction
      mixture leads to an increase in the epoxide yield. A correlation between the
      Lewis acidity of the Mn(iii) center as tuned by the substituents on the phenolate
      ligand, and the epoxide yield and product selectivity has been observed. The
      present complexes act as better chemoselective catalysts for epoxidation of
      cyclohexene and styrene rather than cyclooctene. 

PMID- 24121483
TI  - Collaborational effect of heterolytic layered configuration for enhancement of
      microwave heating.
AB  - Microwave irradiation efficiently heats up the microwave-inert materials in the
      range of applied frequencies when two microwave-inert materials are brought into
      contact in the layered configuration. This heating is applied for annealing TiO2
      nanoporous films for dye-sensitized solar cells achieving a one order of
      magnitude more rapid annealing process for comparable performances. 

PMID- 24121482
TI  - Activity-based protein profiling of secreted cellulolytic enzyme activity
      dynamics in Trichoderma reesei QM6a, NG14, and RUT-C30.
AB  - Lignocellulosic biomass has great promise as a highly abundant and renewable
      source for the production of biofuels. However, the recalcitrant nature of
      lignocellulose toward hydrolysis into soluble sugars remains a significant
      challenge to harnessing the potential of this source of bioenergy. A primary
      method for deconstructing lignocellulose is via chemical treatments, high
      temperatures, and hydrolytic enzyme cocktails, many of which are derived from the
      fungus Trichoderma reesei. Herein, we use an activity-based probe for glycoside
      hydrolases to rapidly identify optimal conditions for maximum enzymatic
      lignocellulose deconstruction. We also demonstrate that subtle changes to enzyme
      composition and activity in various strains of T. reesei can be readily
      characterized by our probe approach. The approach also permits multimodal
      measurements, including fluorescent gel-based analysis of activity in response to
      varied conditions and treatments, and mass spectrometry-based quantitative
      identification of labelled proteins. We demonstrate the promise this probe
      approach holds to facilitate rapid production of enzyme cocktails for high
      efficiency lignocellulose deconstruction to accommodate high-yield biofuel
      production. 

PMID- 24121484
TI  - Brain injury associated with neonatal extracorporeal membrane oxygenation in the
      Netherlands: a nationwide evaluation spanning two decades.
AB  - OBJECTIVE: To determine the prevalence of and to classify ultrasound-proven brain
      injury during neonatal extracorporeal membrane oxygenation in The Netherlands.
      DESIGN: Retrospective nationwide study (Rotterdam and Nijmegen), spanning two
      decades. SETTING: Level III university hospitals. SUBJECTS: All neonates who
      underwent neonatal extracorporeal membrane oxygenation from 1989 to 2010.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cranial ultrasound images
      were reviewed independently by two investigators without knowledge of primary
      diagnosis, outcome, type of extracorporeal membrane oxygenation, or statistics.
      The scans were reviewed for lesion type and timing, with the use of a refined
      classification method for focal brain injury. Extracorporeal membrane oxygenation
      type was venoarterial in 88%. Brain abnormalities were detected in 17.3%: primary
      hemorrhage was most frequent (8.8%). Stroke was identified in 5% of the total
      group, with a notable significant preference for the left hemisphere (in 70%).
      Lobar hematoma (prevalence 2.2 %) was also significantly left predominant.
      CONCLUSION: The incidence of brain injury found with cranial ultrasound in The
      Netherlands of the patients treated with extracorporeal membrane oxygenation
      during the neonatal period was 17.3%. Primary hemorrhage was the largest group of
      lesions, not clearly side-specific except for lobar bleeding, most probably
      related to changes in venous flow. Arterial ischemic stroke occurred predominant
      in the left hemisphere.

PMID- 24121485
TI  - Glioblastoma stem cells are regulated by interleukin-8 signaling in a tumoral
      perivascular niche.
AB  - Glioblastoma multiforme contains a subpopulation of cancer stem-like cells (CSC)
      believed to underlie tumorigenesis and therapeutic resistance. Recent studies
      have localized CSCs in this disease adjacent to endothelial cells (EC) in what
      has been termed a perivascular niche, spurring investigation into the role of EC
      CSC interactions in glioblastoma multiforme pathobiology. However, these studies
      have been limited by a lack of in vitro models of three-dimensional disease that
      can recapitulate the relevant conditions of the niche. In this study, we
      engineered a scaffold-based culture system enabling brain endothelial cells to
      form vascular networks. Using this system, we showed that vascular assembly
      induces CSC maintenance and growth in vitro and accelerates tumor growth in vivo
      through paracrine interleukin (IL)-8 signaling. Relative to conventional
      monolayers, endothelial cells cultured in this three-dimensional system not only
      secreted enhanced levels of IL-8 but also induced CSCs to upregulate the IL-8
      cognate receptors CXCR1 and CXCR2, which collectively enhanced CSC migration,
      growth, and stemness properties. CXCR2 silencing in CSCs abolished the tumor
      promoting effects of endothelial cells in vivo, confirming a critical role for
      this signaling pathway in GMB pathogenesis. Together, our results reveal
      synergistic interactions between endothelial cells and CSCs that promote the
      malignant properties of CSCs in an IL-8-dependent manner. Furthermore, our
      findings underscore the relevance of tissue-engineered cell culture platforms to
      fully analyze signaling mechanisms in the tumor microenvironment.

PMID- 24121486
TI  - Maintenance of androgen receptor inactivation by S-nitrosylation.
AB  - Antiandrogens target ligand-binding domain of androgen receptor (AR) and are used
      as first-line therapeutics to treat patients diagnosed with locally advanced and
      metastatic prostate cancer. Although initially beneficial as judged with actual
      tumor mass shrinkage, this therapy invariably fails and the cancer reappears as
      castration-resistant disease. Here, we report that increased intracellular nitric
      oxide (NO) levels lead to growth inhibition of both androgen-dependent and
      castration-resistant prostate tumors through a mechanism that involves AR
      function inactivation by S-nitrosylation of a single C601 residue present in the
      DNA-binding domain. AR S-nitrosylation does not impact its subcellular
      distribution but attenuates its ability to bind AR-responsive elements in
      promoter region of target genes. Mechanistically, AR is transnitrosylated by its
      partner HSP90 protein. Ubiquitous small-molecule NO donors promote the AR S
      nitrosylation and inhibit growth of castration-resistant prostate tumors. These
      findings reveal a new mechanism of regulating AR function and suggest that
      sequential targeting of distinct domains of AR may extend therapeutic efficacy
      for patients with advanced prostate cancer.

PMID- 24121487
TI  - TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of
      early disease and disease recurrence in urine.
AB  - Activating mutations occur in the promoter of the telomerase reverse
      transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To
      explore their role in bladder cancer development and to assess their utility as
      urine markers for early detection, we sequenced the TERT promoter in 76 well
      characterized papillary and flat noninvasive urothelial carcinomas, including 28
      pTa low-grade transitional cell carcinomas (TCC), 31 pTa high-grade TCCs, and 17
      pTis carcinoma in situ lesions. We also evaluated the sequence of the TERT
      promoter in a separate series of 14 early bladder neoplasms and matched follow-up
      urine samples to determine whether urine TERT status was an indicator of disease
      recurrence. A high rate of TERT promoter mutation was observed in both papillary
      and flat lesions, as well as in low- and high-grade noninvasive urothelial
      neoplasms (mean: 74%). In addition, among patients whose tumors harbored TERT
      promoter mutations, the same mutations were present in follow-up urines in seven
      of eight patients that recurred but in none of the six patients that did not
      recur (P < 0.001). TERT promoter mutations occur in both papillary and flat
      lesions, are the most frequent genetic alterations identified to date in
      noninvasive precursor lesions of the bladder, are detectable in urine, and seem
      to be strongly associated with bladder cancer recurrence. These provocative
      results suggest that TERT promoter mutations may offer a useful urinary biomarker
      for both early detection and monitoring of bladder neoplasia.

PMID- 24121489
TI  - Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor
      resistant melanoma.
AB  - The mitogen-activated protein kinase (MAPK) pathway is particularly important for
      the survival and proliferation of melanoma cells. Somatic mutations in BRAF and
      NRAS are frequently observed in melanoma. Recently, the BRAF inhibitors
      vemurafenib and dabrafenib have emerged as promising agents for the treatment of
      melanoma patients with BRAF-activating mutations. However, as BRAF inhibitors
      induce RAF paradoxical activation via RAF dimerization in BRAF wild-type cells,
      rapid emergence of acquired resistance and secondary skin tumors as well as
      presence of few effective treatment options for melanoma bearing wild-type BRAF
      (including NRAS-mutant melanoma) are clinical concerns. Here, we demonstrate that
      the selective pan-RAF inhibitor TAK-632 suppresses RAF activity in BRAF wild-type
      cells with minimal RAF paradoxical activation. Our analysis using RNAi and TAK
      632 in preclinical models reveals that the MAPK pathway of NRAS-mutated melanoma
      cells is highly dependent on RAF. We also show that TAK-632 induces RAF
      dimerization but inhibits the kinase activity of the RAF dimer, probably because
      of its slow dissociation from RAF. As a result, TAK-632 demonstrates potent
      antiproliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated
      melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation
      or BRAF truncation. Furthermore, we demonstrate that the combination of TAK-632
      and the MAPK kinase (MEK) inhibitor TAK-733 exhibits synergistic
      antiproliferative effects on these cells. Our findings characterize the unique
      features of TAK-632 as a pan-RAF inhibitor and provide rationale for its further
      investigation in NRAS-mutated melanoma and a subset of BRAF-mutated melanomas
      refractory to BRAF inhibitors.

PMID- 24121488
TI  - Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome
      insulin resistance and exert pronounced antitumor efficacy.
AB  - The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well
      established, but clinical translation of PI3K inhibitors has been limited by
      feedback signaling, suboptimal intratumoral concentration, and an insulin
      resistance "class effect." This study was designed to explore the use of
      supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and
      potentially overcome these limitations. PI3K inhibitor structures were rationally
      modified using a cholesterol-based derivative, facilitating supramolecular
      nanoassembly with L-alpha-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-N-[amino(polythylene glycol)]. The supramolecular
      nanoparticles (SNP) that were assembled were physicochemically characterized and
      functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using
      4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with
      effects on glucose homeostasis evaluated using an insulin sensitivity test. The
      use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted
      the need to keep design principles in perspective; specifically, potency of the
      active molecule and the linker chemistry were critical principles for efficacy,
      similar to antibody-drug conjugates. We found that the SNPs exerted a temporally
      sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo.
      These effects were associated with increased antitumor efficacy and survival as
      compared with PI103 and PI828. Efficacy was further increased by decorating the
      nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs
      abrogated the insulin resistance that has been associated widely with other PI3K
      inhibitors. This study provides a preclinical foundation for the use of
      supramolecular nanochemistry to overcome current challenges associated with PI3K
      inhibitors, offering a paradigm for extension to other molecularly targeted
      therapeutics being explored for cancer treatment.

PMID- 24121490
TI  - The HSP90 inhibitor ganetespib synergizes with the MET kinase inhibitor
      crizotinib in both crizotinib-sensitive and -resistant MET-driven tumor models.
AB  - The proto-oncogene MET is aberrantly activated via overexpression or mutation in
      numerous cancers, making it a prime anticancer molecular target. However, the
      clinical success of MET-directed tyrosine kinase inhibitors (TKI) has been
      limited due, in part, to mutations in the MET kinase domain that confer
      therapeutic resistance. Circumventing this problem remains a key challenge to
      improving durable responses in patients receiving MET-targeted therapy. MET is an
      HSP90-dependent kinase, and in this report we show that HSP90 preferentially
      interacts with and stabilizes activated MET, regardless of whether the activation
      is ligand-dependent or is a consequence of kinase domain mutation. In contrast,
      many MET-TKI show a preference for the inactive form of the kinase, and
      activating mutations in MET can confer resistance. Combining the HSP90 inhibitor
      ganetespib with the MET-TKI crizotinib achieves synergistic inhibition of MET,
      its downstream signaling pathways, and tumor growth in both TKI-sensitive and 
      resistant MET-driven tumor models. These data suggest that inclusion of an HSP90
      inhibitor can partially restore TKI sensitivity to previously resistant MET
      mutants, and they provide the foundation for clinical evaluation of this
      therapeutic combination in patients with MET-driven cancers.

PMID- 24121491
TI  - Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth.
AB  - One classical feature of cancer cells is their metabolic acquisition of a highly
      glycolytic phenotype. Carbon monoxide (CO), one of the products of the
      cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been
      implicated in carcinogenesis and therapeutic resistance. However, the functional
      contributions of CO and HO-1 to these processes are poorly defined. In human
      prostate cancers, we found that HO-1 was nuclear localized in malignant cells,
      with low enzymatic activity in moderately differentiated tumors correlating with
      relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer
      cells but not normal cells to chemotherapy, with growth arrest and apoptosis
      induced in vivo in part through mitotic catastrophe. CO targeted mitochondria
      activity in cancer cells as evidenced by higher oxygen consumption, free radical
      generation, and mitochondrial collapse. Collectively, our findings indicated that
      CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell
      bioenergetics, ultimately resulting in metabolic exhaustion.

PMID- 24121492
TI  - In vivo MAPK reporting reveals the heterogeneity in tumoral selection of
      resistance to RAF inhibitors.
AB  - Activation of the ERK1/2 mitogen-activated protein kinases (MAPK) confers
      resistance to the RAF inhibitors vemurafenib and dabrafenib in mutant BRAF-driven
      melanomas. Methods to understand how resistance develops are important to
      optimize the clinical use of RAF inhibitors in patients. Here, we report the
      development of a novel ERK1/2 reporter system that provides a noninvasive,
      quantitative, and temporal analysis of RAF inhibitor efficacy in vivo. Use of
      this system revealed heterogeneity in the level of ERK1/2 reactivation associated
      with acquired resistance to RAF inhibition. We identified several distinct novel
      and known molecular changes in resistant tumors emerging from treatment-naive
      cell populations including BRAF V600E variants and HRAS mutation, both of which
      were required and sufficient for ERK1/2 reactivation and drug resistance. Our
      work offers an advance in understanding RAF inhibitor resistance and the
      heterogeneity in resistance mechanisms, which emerge from a malignant cell
      population.

PMID- 24121493
TI  - Neuropilin-2 Is upregulated in lung cancer cells during TGF-beta1-induced
      epithelial-mesenchymal transition.
AB  - The epithelial-mesenchymal transition (EMT) and its reversal, mesenchymal
      epithelial transition (MET), are fundamental processes involved in tumor cell
      invasion and metastasis. SEMA3F is a secreted semaphorin and tumor suppressor
      downregulated by TGF-beta1 and ZEB1-induced EMT. Here, we report that neuropilin
      (NRP)-2, the high-affinity receptor for SEMA3F and a coreceptor for certain
      growth factors, is upregulated during TGF-beta1-driven EMT in lung cancer cells.
      Mechanistically, NRP2 upregulation was TbetaRI dependent and SMAD independent,
      occurring mainly at a posttranscriptional level involving increased association
      of mRNA with polyribosomes. Extracellular signal-regulated kinase (ERK) and AKT
      inhibition blocked NRP2 upregulation, whereas RNA interference-mediated
      attenuation of ZEB1 reduced steady-state NRP2 levels. In addition, NRP2
      attenuation inhibited TGF-beta1-driven morphologic transformation,
      migration/invasion, ERK activation, growth suppression, and changes in gene
      expression. In a mouse xenograft model of lung cancer, NRP2 attenuation also
      inhibited locally invasive features of the tumor and reversed TGF-beta1-mediated
      growth inhibition. In support of these results, human lung cancer specimens with
      the highest NRP2 expression were predominantly E-cadherin negative. Furthermore,
      the presence of NRP2 staining strengthened the association of E-cadherin loss
      with high-grade tumors. Together, our results demonstrate that NRP2 contributes
      significantly to TGF-beta1-induced EMT in lung cancer.

PMID- 24121495
TI  - Soluble carcinoembryonic antigen activates endothelial cells and tumor
      angiogenesis.
AB  - Carcinoembryonic antigen (CEA, CD66e, CEACAM-5) is a cell-surface-bound
      glycoprotein overexpressed and released by many solid tumors that has an
      autocrine function in cancer cell survival and differentiation. Soluble CEA
      released by tumors is present in the circulation of patients with cancer, where
      it is used as a marker for cancer progression, but whether this form of CEA
      exerts any effects in the tumor microenvironment is unknown. Here, we present
      evidence that soluble CEA is sufficient to induce proangiogenic endothelial cell
      behaviors, including adhesion, spreading, proliferation, and migration in vitro
      and tumor microvascularization in vivo. CEA-induced activation of endothelial
      cells was dependent on integrin beta-3 signals that activate the focal-adhesion
      kinase and c-Src kinase and their downstream MAP-ERK kinase/extracellular signal
      regulated kinase and phosphoinositide 3-kinase/Akt effector pathways. Notably,
      while interference with VEGF signaling had no effect on CEA-induced endothelial
      cell activation, downregulation with the CEA receptor in endothelial cells
      attenuated CEA-induced signaling and tumor angiogenesis. Corroborating these
      results clinically, we found that tumor microvascularization was higher in
      patients with colorectal cancer exhibiting higher serum levels of soluble CEA.
      Together, our results elucidate a novel function for soluble CEA in tumor
      angiogenesis.

PMID- 24121494
TI  - Sequential application of a cytotoxic nanoparticle and a PI3K inhibitor enhances
      antitumor efficacy.
AB  - Nanomedicines that preferentially deploy cytotoxic agents to tumors and molecular
      targeted therapeutics that inhibit specific aberrant oncogenic drivers are
      emerging as the new paradigm for the management of cancer. While combination
      therapies are a mainstay of cancer chemotherapy, few studies have addressed the
      combination of nanomedicines and molecular targeted therapeutics. Furthermore,
      limited knowledge exists on the impact of sequencing of such therapeutics and
      nanomedicines on the antitumor outcome. Here, we engineered a supramolecular cis
      platinum nanoparticle, which induced apoptosis in breast cancer cells but also
      elicited prosurvival signaling via an EGF receptor/phosphoinositide 3-kinase
      (PI3K) pathway. A combination of mathematical modeling and in vitro and in vivo
      validation using a pharmacologic inhibitor of PI3K, PI828, demonstrate that
      administration of PI828 following treatment with the supramolecular cis-platinum
      nanoparticle results in enhanced antitumor efficacy in breast cancer as compared
      with when the sequence is reversed or when the two treatments are administered
      simultaneously. This study addresses, for the first time, the impact of drug
      sequencing in the case of a combination of a nanomedicine and a targeted
      therapeutic. Furthermore, our results indicate that a rational combination of cis
      platinum nanoparticles and a PI3K-targeted therapeutic can emerge as a potential
      therapy for breast cancer.

PMID- 24121496
TI  - Androgen glucuronidation: an unexpected target for androgen deprivation therapy,
      with prognosis and diagnostic implications.
AB  - Androgen deprivation therapy (ADTh) remains a mainstay of prostate cancer
      treatment, but its efficacy is bypassed by mechanisms that are not fully
      understood. In human prostate cancer cells, androgen glucuronidation, catalyzed
      by the two UDP-glucuronosyltransferase (UGT) enzymes UGT2B15 and UGT2B17, is the
      major androgen inactivation pathway. In this study, we investigated the effect of
      ADTh on androgen glucuronidation to evaluate its potential clinical utility for
      prostate cancer prognosis or therapy. UGT2B15 and UGT2B17 expression was
      evaluated in prostate cancer specimens from untreated or treated patients and in
      cell models of prostate cancer exposed to clinically relevant antiandrogens.
      UGT2B15 and UGT2B17 protein levels in prostate were increased after 5 months of
      ADTh when compared with specimens from untreated patients. UGT2B15 expression
      remained elevated for up to 12 months, but UGT2B17 returned to initial levels as
      soon as after 6 months. Several androgen receptor (AR) antagonists tested caused
      a dose- and time-dependent stimulation of UGT2B15 and UGT2B17 expression and
      androgen glucuronidation in prostate cancer cell lines. The role of AR in these
      regulatory events was confirmed using AR-deficient LNCaP cells, in which UGT2B
      attenuation reduced the antiproliferative effects of AR pharmacologic
      antagonists. Through this combination of clinical and functional investigations,
      our work revealed that ADTh stimulates a local androgen metabolism in prostate
      cells, establishing a foundation to evaluate the potential of UGT2B15 and UGT2B17
      as drug targets and/or molecular markers for ADTh responsiveness and maintenance
      in prostate cancer.

PMID- 24121497
TI  - The cardiac model of rehabilitation for reducing cardiovascular risk factors post
      transient ischaemic attack and stroke: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of a standard National
      Health Service cardiac rehabilitation programme on risk factor reduction for
      patients after a minor stroke and transient ischaemic attack. DESIGN: Single
      blind randomized controlled trial. SETTING: Cardiac rehabilitation classes.
      SUBJECTS: Twenty-four patients. INTERVENTION: All participants received standard
      care. In addition, the intervention group undertook an eight-week cardiac
      rehabilitation programme consisting of weekly exercise and education classes.
      OUTCOME MEASURES: Cardiovascular disease risk score; lipid profiles; resting
      blood pressure; C-reactive protein (measured with a high sensitive assay) and
      fibrinogen levels; blood glucose; obesity; physical activity levels; subjective
      health status (SF-36); Hospital Anxiety and Depression Scale. RESULTS: Group
      comparison with independent t-tests showed a significantly greater improvement in
      the cardiovascular disease risk score for participants in the intervention group
      compared to standard care (intervention 25.7 +/- 22.8 to 23.15 +/- 18.3, control
      25.03 +/- 15.4 to 27.12 +/- 16.1, t = -1.81, P < 0.05). There were also
      significant improvements for the intervention group in activity levels
      (intervention 9.41 +/- 7.7 to 8.08 +/- 5.7, control 14.50 +/- 5.5 to 9.83 +/-
      6.6, t = -2.00, P < 0.05) and the SF-36 domains of physical functioning
      (intervention 70 +/- 24.6 to 75.4 +/- 11.1, control 90.00 +/- 12.4 to 83.16 +/-
      17.3, t = -2.72, P < 0.05) and mental health (intervention 84 +/- 40 to 92 +/-
      40, control 88.00 +/- 60 to 84 +/- 44, z = -2.06, P < 0.05). CONCLUSION: The
      results suggest that standard cardiac rehabilitation programmes are a feasible
      and effective means of reducing the risk of future cardiovascular events for
      patients after minor stroke and transient ischaemic attack.

PMID- 24121498
TI  - Genome-wide survey on genomic variation, expression divergence, and evolution in
      two contrasting rice genotypes under high salinity stress.
AB  - Expression profiling is one of the most important tools for dissecting biological
      functions of genes and the upregulation or downregulation of gene expression is
      sufficient for recreating phenotypic differences. Expression divergence of genes
      significantly contributes to phenotypic variations. However, little is known on
      the molecular basis of expression divergence and evolution among rice genotypes
      with contrasting phenotypes. In this study, we have implemented an integrative
      approach using bioinformatics and experimental analyses to provide insights into
      genomic variation, expression divergence, and evolution between salinity
      sensitive rice variety Nipponbare and tolerant rice line Pokkali under normal and
      high salinity stress conditions. We have detected thousands of differentially
      expressed genes between these two genotypes and thousands of up- or downregulated
      genes under high salinity stress. Many genes were first detected with expression
      evidence using custom microarray analysis. Some gene families were preferentially
      regulated by high salinity stress and might play key roles in stress-responsive
      biological processes. Genomic variations in promoter regions resulted from single
      nucleotide polymorphisms, indels (1-10 bp of insertion/deletion), and structural
      variations significantly contributed to the expression divergence and regulation.
      Our data also showed that tandem and segmental duplication, CACTA and hAT
      elements played roles in the evolution of gene expression divergence and
      regulation between these two contrasting genotypes under normal or high salinity
      stress conditions. 

PMID- 24121499
TI  - Apolipoproteins C-I and C-III inhibit lipoprotein lipase activity by displacement
      of the enzyme from lipid droplets.
AB  - Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL)
      activity, but the molecular mechanisms for this remain obscure. We present
      evidence that either apoC-I or apoC-III, when bound to triglyceride-rich
      lipoproteins, prevent binding of LPL to the lipid/water interface. This results
      in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed
      that hydrophobic amino acid residues centrally located in the apoC-III molecule
      are critical for attachment to lipid emulsion particles and consequently
      inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and
      protect the enzyme from inactivating factors such as angiopoietin-like protein 4
      (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich
      particles severely diminished their protective effect on LPL and rendered the
      enzyme more susceptible to inactivation by angptl4. These observations were seen
      using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the
      presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was
      needed for displacement of LPL from the lipid/water interface. In conclusion, we
      show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid
      emulsion particles. We also propose a role for these apolipoproteins in the
      irreversible inactivation of LPL by factors such as angptl4. 

PMID- 24121500
TI  - Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by
      deacetylating conserved lysines near the active site.
AB  - Long-chain acyl-CoA dehydrogenase (LCAD) is a key mitochondrial fatty acid
      oxidation enzyme. We previously demonstrated increased LCAD lysine acetylation in
      SIRT3 knockout mice concomitant with reduced LCAD activity and reduced fatty acid
      oxidation. To study the effects of acetylation on LCAD and determine sirtuin 3
      (SIRT3) target sites, we chemically acetylated recombinant LCAD. Acetylation
      impeded substrate binding and reduced catalytic efficiency. Deacetylation with
      recombinant SIRT3 partially restored activity. Residues Lys-318 and Lys-322 were
      identified as SIRT3-targeted lysines. Arginine substitutions at Lys-318 and Lys
      322 prevented the acetylation-induced activity loss. Lys-318 and Lys-322 flank
      residues Arg-317 and Phe-320, which are conserved among all acyl-CoA
      dehydrogenases and coordinate the enzyme-bound FAD cofactor in the active site.
      We propose that acetylation at Lys-318/Lys-322 causes a conformational change
      which reduces hydride transfer from substrate to FAD. Medium-chain acyl-CoA
      dehydrogenase and acyl-CoA dehydrogenase 9, two related enzymes with lysines at
      positions equivalent to Lys-318/Lys-322, were also efficiently deacetylated by
      SIRT3 following chemical acetylation. These results suggest that
      acetylation/deacetylation at Lys-318/Lys-322 is a mode of regulating fatty acid
      oxidation. The same mechanism may regulate other acyl-CoA dehydrogenases. 

PMID- 24121501
TI  - A conserved protein with AN1 zinc finger and ubiquitin-like domains modulates
      Cdc48 (p97) function in the ubiquitin-proteasome pathway.
AB  - Regulated protein degradation mediated by the ubiquitin-proteasome system (UPS)
      is critical to eukaryotic protein homeostasis. Often vital to degradation of
      protein substrates is their disassembly, unfolding, or extraction from membranes.
      These processes are catalyzed by the conserved AAA-ATPase Cdc48 (also known as
      p97). Here we characterize the Cuz1 protein (Cdc48-associated UBL/zinc finger
      protein-1), encoded by a previously uncharacterized arsenite-inducible gene in
      budding yeast. Cuz1, like its human ortholog ZFAND1, has both an AN1-type zinc
      finger (Zf_AN1) and a divergent ubiquitin-like domain (UBL). We show that Cuz1
      modulates Cdc48 function in the UPS. The two proteins directly interact, and the
      Cuz1 UBL, but not Zf_AN1, is necessary for binding to the Cdc48 N-terminal
      domain. Cuz1 also associates, albeit more weakly, with the proteasome, and the
      UBL is dispensable for this interaction. Cuz1-proteasome interaction is strongly
      enhanced by exposure of cells to the environmental toxin arsenite, and in a
      proteasome mutant, loss of Cuz1 enhances arsenite sensitivity. Whereas loss of
      Cuz1 alone causes only minor UPS degradation defects, its combination with
      mutations in the Cdc48(Npl4-Ufd1) complex leads to much greater impairment. Cuz1
      helps limit the accumulation of ubiquitin conjugates on both the proteasome and
      Cdc48, suggesting a possible role in the transfer of ubiquitylated substrates
      from Cdc48 to the proteasome or in their release from these complexes. 

PMID- 24121502
TI  - Involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase
      mediated signaling transduction.
AB  - Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate
      sodium reabsorption in the renal proximal tubule. We report here that reactive
      oxygen species are required to initiate ouabain-stimulated Na/K-ATPase.c-Src
      signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented
      ouabain-stimulated Na/K-ATPase.c-Src signaling, protein carbonylation,
      redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and
      inhibition of active transepithelial (22)Na(+) transport. Disruption of the Na/K
      ATPase.c-Src signaling complex attenuated ouabain-stimulated protein
      carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal
      of ouabain, and this reversibility is largely independent of de novo protein
      synthesis and degradation by either the lysosome or the proteasome pathways.
      Furthermore, ouabain stimulated direct carbonylation of two amino acid residues
      in the actuator domain of the Na/K-ATPase alpha1 subunit. Taken together, the
      data indicate that carbonylation modification of the Na/K-ATPase alpha1 subunit
      is involved in a feed-forward mechanism of regulation of ouabain-mediated renal
      proximal tubule Na/K-ATPase signal transduction and subsequent sodium transport.

PMID- 24121503
TI  - Chemotype-selective modes of action of kappa-opioid receptor agonists.
AB  - The crystal structures of opioid receptors provide a novel platform for inquiry
      into opioid receptor function. The molecular determinants for activation of the
      kappa-opioid receptor (KOR) were studied using a combination of agonist docking,
      functional assays, and site-directed mutagenesis. Eighteen positions in the
      putative agonist binding site of KOR were selected and evaluated for their
      effects on receptor binding and activation by ligands representing four distinct
      chemotypes: the peptide dynorphin A(1-17), the arylacetamide U-69593, and the non
      charged ligands salvinorin A and the octahydroisoquinolinone carboxamide 1xx.
      Minimally biased docking of the tested ligands into the antagonist-bound KOR
      structure generated distinct binding modes, which were then evaluated
      biochemically and pharmacologically. Our analysis identified two types of
      mutations: those that affect receptor function primarily via ligand binding and
      those that primarily affect function. The shared and differential mechanisms of
      agonist binding and activation in KOR are further discussed. Usually, mutations
      affecting function more than binding were located at the periphery of the binding
      site and did not interact strongly with the various ligands. Analysis of the
      crystal structure along with the present results provide fundamental insights
      into the activation mechanism of the KOR and suggest that "functional" residues,
      along with water molecules detected in the crystal structure, may be directly
      involved in transduction of the agonist binding event into structural changes at
      the conserved rotamer switches, thus leading to receptor activation. 

PMID- 24121504
TI  - Structure of the homodimeric glycine decarboxylase P-protein from Synechocystis
      sp. PCC 6803 suggests a mechanism for redox regulation.
AB  - Glycine decarboxylase, or P-protein, is a pyridoxal 5'-phosphate (PLP)-dependent
      enzyme in one-carbon metabolism of all organisms, in the glycine and serine
      catabolism of vertebrates, and in the photorespiratory pathway of oxygenic
      phototrophs. P-protein from the cyanobacterium Synechocystis sp. PCC 6803 is an
      alpha2 homodimer with high homology to eukaryotic P-proteins. The crystal
      structure of the apoenzyme shows the C terminus locked in a closed conformation
      by a disulfide bond between Cys(972) in the C terminus and Cys(353) located in
      the active site. The presence of the disulfide bridge isolates the active site
      from solvent and hinders the binding of PLP and glycine in the active site.
      Variants produced by substitution of Cys(972) and Cys(353) by Ser using site
      directed mutagenesis have distinctly lower specific activities, supporting the
      crucial role of these highly conserved redox-sensitive amino acid residues for P
      protein activity. Reduction of the 353-972 disulfide releases the C terminus and
      allows access to the active site. PLP and the substrate glycine bind in the
      active site of this reduced enzyme and appear to cause further conformational
      changes involving a flexible surface loop. The observation of the disulfide bond
      that acts to stabilize the closed form suggests a molecular mechanism for the
      redox-dependent activation of glycine decarboxylase observed earlier. 

PMID- 24121505
TI  - A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are major sheddases of T
      cell immunoglobulin and mucin domain 3 (Tim-3).
AB  - T cell immunoglobulin and mucin domain 3 (Tim-3) dampens the response of CD4(+)
      and CD8(+) effector T cells via induction of cell death and/or T cell exhaustion
      and enhances the ability of macrophages to clear pathogens via binding to
      galectin 9. Here we provide evidence that human Tim-3 is a target of A
      disintegrin and metalloprotease (ADAM)-mediated ectodomain shedding resulting in
      a soluble form of Tim-3. We identified ADAM10 and ADAM17 as major sheddases of
      Tim-3 as shown by ADAM-specific inhibitors and the ADAM10 pro-domain in HEK293
      cells and ADAM10/ADAM17-deficient murine embryonic fibroblasts. PMA-induced
      shedding of Tim-3 was abrogated by deletion of amino acids Glu(181)-Asp(190) of
      the stalk region and Tim-3 lacking the intracellular domain was not efficiently
      cleaved after PMA stimulation. Surprisingly, a single lysine residue within the
      intracellular domain rescues shedding of Tim-3. Shedding of endogenous Tim-3 was
      found in primary human CD14(+) monocytes after PMA and ionomycin stimulation.
      Importantly, the recently described down-regulation of Tim-3 from Toll-like
      receptor-activated CD14(+) monocytes was caused by ADAM10- and ADAM17-mediated
      shedding. Inhibition of Tim-3 shedding from lipopolysaccharide-induced monocytes
      did not influence lipopolysaccharide-induced TNFalpha and IL-6 but increases IL
      12 expression. In summary, we describe Tim-3 as novel target for ADAM-mediated
      ectodomain shedding and suggest a role of Tim-3 shedding in TLR-mediated immune
      responses of CD14(+) monocytes. 

PMID- 24121506
TI  - Structural determinants of the insulin receptor-related receptor activation by
      alkali.
AB  - IRR is a member of the insulin receptor (IR) family that does not have any known
      agonist of a peptide nature but can be activated by mildly alkaline medium and
      was thus proposed to function as an extracellular pH sensor. IRR activation by
      alkali is defined by its N-terminal extracellular region. To reveal key
      structural elements involved in alkali sensing, we developed an in vitro method
      to quantify activity of IRR and its mutants. Replacing the IRR L1C domains
      (residues 1-333) or L2 domain (residues 334-462) or both with the homologous
      fragments of IR reduced the receptor activity to 35, 64, and 7% percent,
      respectively. Within L1C domains, five amino acid residues (Leu-135, Gly-188, Arg
      244, and vicinal His-318 and Lys-319) were identified as IRR-specific by species
      conservation analysis of the IR family. These residues are exposed and located in
      junctions between secondary structure folds. The quintuple mutation of these
      residues to alanine had the same negative effect as the entire L1C domain
      replacement, whereas none of the single mutations was as effective. Separate
      mutations of these five residues and of L2 produced partial negative effects that
      were additive. The pH dependence of cell-expressed mutants (L1C and L2 swap, L2
      plus triple LGR mutation, and L2 plus quintuple LGRHK mutation) was shifted
      toward alkalinity and, in contrast with IRR, did not show significant positive
      cooperativity. Our data suggest that IRR activation is not based on a single
      residue deprotonation in the IRR ectodomain but rather involves synergistic
      conformational changes at multiple points. 

PMID- 24121507
TI  - p62/sequestosome-1 up-regulation promotes ABT-263-induced caspase-8
      aggregation/activation on the autophagosome.
AB  - Autophagy and apoptosis regulate cancer cell viability in response to cytotoxic
      stress; however, their functional relationship remains unclear. p62/sequestosome
      1 is a multifunctional protein and a signaling hub that shuttles ubiquitinated
      proteins to the lysosome during autophagy. Autophagy inhibition up-regulates p62,
      and prior data suggest that p62 may mediate apoptosis. Here, we demonstrate that
      p62 can regulate a caspase-8-dependent apoptosis in response to the BH3 mimetic
      agent, ABT-263. Up-regulation of p62 was shown to enhance ABT-263-induced caspase
      8 activation that was Bax-dependent and resulted from mitochondrial
      amplification. Dependence upon caspase-8 was confirmed using caspase-8-deficient
      cells and by caspase-8 siRNA. Ectopic wild-type p62, but not p62 mutants with
      loss of ability to promote apoptosis, was shown to co-localize with caspase-8 and
      to promote its self-aggregation in ABT-263-treated cells, shown using a
      bimolecular fluorescence complementation assay. Endogenous p62 co-localized with
      caspase-8 in the presence of ABT-263 plus an autophagy inhibitor. Caspase-8 was
      shown to interact and co-localize with the autophagosome marker, LC3II. Knockdown
      of p62 attenuated binding between caspase-8 and LC3II, whereas p62 overexpression
      enhanced the co-localization of caspase-8 aggregates with LC3. LC3 knockdown did
      not affect interaction between caspase-8 and p62, suggesting that p62 may
      facilitate caspase-8 translocation to the autophagosomal membrane. A direct
      activator of caspase-8, i.e., TRAIL, alone or combined with ABT-263, induced
      caspase-8 aggregation and co-localization with p62 that was associated with a
      synergistic drug interaction. Together, these results demonstrate that up
      regulation of p62 can mediate apoptosis via caspase-8 in the setting of autophagy
      inhibition. 

PMID- 24121508
TI  - A knock-in mouse model of human PHD2 gene-associated erythrocytosis establishes a
      haploinsufficiency mechanism.
AB  - The central pathway for controlling red cell mass is the PHD (prolyl hydroxylase
      domain protein):hypoxia-inducible factor (HIF) pathway. HIF, which is negatively
      regulated by PHD, activates numerous genes, including ones involved in
      erythropoiesis, such as the ERYTHROPOIETIN (EPO) gene. Recent studies have
      implicated PHD2 as the key PHD isoform regulating red cell mass. Studies of
      humans have identified erythrocytosis-associated, heterozygous point mutations in
      the PHD2 gene. A key question concerns the mechanism by which human mutations
      lead to phenotypes. In the present report, we generated and characterized a mouse
      line in which a P294R knock-in mutation has been introduced into the mouse Phd2
      locus to model the first reported human PHD2 mutation (P317R). Phd2(P294R/+) mice
      display a degree of erythrocytosis equivalent to that seen in Phd2(+/-) mice. The
      Phd2(P294R/+)-associated erythrocytosis is reversed in a Hif2a(+/-), but not a
      Hif1a(+/-) background. Additional studies using various conditional knock-outs of
      Phd2 reveal that erythrocytosis can be induced by homozygous and heterozygous
      knock-out of Phd2 in renal cortical interstitial cells using a Pax3-Cre transgene
      or by homozygous knock-out of Phd2 in hematopoietic progenitors driven by a Vav1
      Cre transgene. These studies formally prove that a missense mutation in PHD2 is
      the cause of the erythrocytosis, show that this occurs through
      haploinsufficiency, and point to multifactorial control of red cell mass by PHD2.

PMID- 24121509
TI  - In vivo epithelial wound repair requires mobilization of endogenous intracellular
      and extracellular calcium.
AB  - We report that a localized intracellular and extracellular Ca(2+) mobilization
      occurs at the site of microscopic epithelial damage in vivo and is required to
      mediate tissue repair. Intravital confocal/two-photon microscopy continuously
      imaged the surgically exposed stomach mucosa of anesthetized mice while
      photodamage of gastric epithelial surface cells created a microscopic lesion that
      healed within 15 min. Transgenic mice with an intracellular Ca(2+)-sensitive
      protein (yellow cameleon 3.0) report that intracellular Ca(2+) selectively
      increases in restituting gastric epithelial cells adjacent to the damaged cells.
      Pretreatment with U-73122, indomethacin, 2-aminoethoxydiphenylborane, or
      verapamil inhibits repair of the damage and also inhibits the intracellular
      Ca(2+) increase. Confocal imaging of Fura-Red dye in luminal superfusate shows a
      localized extracellular Ca(2+) increase at the gastric surface adjacent to the
      damage that temporally follows intracellular Ca(2+) mobilization. Indomethacin
      and verapamil also inhibit the luminal Ca(2+) increase. Intracellular Ca(2+)
      chelation (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl
      ester, BAPTA/AM) fully inhibits intracellular and luminal Ca(2+) increases,
      whereas luminal calcium chelation (N-(2-hydroxyetheyl)-ethylendiamin-N,N,N'
      triacetic acid trisodium, HEDTA) blocks the increase of luminal Ca(2+) and
      unevenly inhibits late-phase intracellular Ca(2+) mobilization. Both modes of
      Ca(2+) chelation slow gastric repair. In plasma membrane Ca-ATPase 1(+/-) mice,
      but not plasma membrane Ca-ATPase 4(-/-) mice, there is slowed epithelial repair
      and a diminished gastric surface Ca(2+) increase. We conclude that endogenous
      Ca(2+), mobilized by signaling pathways and transmembrane Ca(2+) transport,
      causes increased Ca(2+) levels at the epithelial damage site that are essential
      to gastric epithelial cell restitution in vivo. 

PMID- 24121510
TI  - Role of AKAP79/150 protein in beta1-adrenergic receptor trafficking and signaling
      in mammalian cells.
AB  - Protein kinase A-anchoring proteins (AKAPs) participate in the formation of
      macromolecular signaling complexes that include protein kinases, ion channels,
      effector enzymes, and G-protein-coupled receptors. We examined the role of
      AKAP79/150 (AKAP5) in trafficking and signaling of the beta1-adrenergic receptor
      (beta1-AR). shRNA-mediated down-regulation of AKAP5 in HEK-293 cells inhibited
      the recycling of the beta1-AR. Recycling of the beta1-AR in AKAP5 knockdown cells
      was rescued by shRNA-resistant AKAP5. However, truncated mutants of AKAP5 with
      deletions in the domains involved in membrane targeting or in binding to
      calcineurin or PKA failed to restore the recycling of the beta1-AR, indicating
      that full-length AKAP5 was required. Furthermore, recycling of the beta1-AR in
      rat neonatal cardiac myocytes was dependent on targeting the AKAP5-PKA complex to
      the C-terminal tail of the beta1-AR. To analyze the role of AKAP5 more directly,
      recycling of the beta1-AR was determined in ventricular myocytes from AKAP5(-/-)
      mice. In AKAP5(-/-) myocytes, the agonist-internalized beta1-AR did not recycle,
      except when full-length AKAP5 was reintroduced. These data indicate that AKAP5
      exerted specific and profound effects on beta1-AR recycling in mammalian cells.
      Biochemical or real time FRET-based imaging of cyclic AMP revealed that deletion
      of AKAP5 sensitized the cardiac beta1-AR signaling pathway to isoproterenol.
      Moreover, isoproterenol-mediated increase in contraction rate, surface area, or
      expression of beta-myosin heavy chains was significantly greater in AKAP5(-/-)
      myocytes than in AKAP5(+/+) myocytes. These results indicate a significant role
      for the AKAP5 scaffold in signaling and trafficking of the beta1-AR in cardiac
      myocytes and mammalian cells. 

PMID- 24121511
TI  - Enterocyte-specific regulation of the apical nutrient transporter SLC6A19
      (B(0)AT1) by transcriptional and epigenetic networks.
AB  - Enterocytes are specialized to absorb nutrients from the lumen of the small
      intestine by expressing a select set of genes to maximize the uptake of
      nutrients. They develop from stem cells in the crypt and differentiate into
      mature enterocytes while moving along the crypt-villus axis. Using the Slc6a19
      gene as an example, encoding the neutral amino acid transporter B(0)AT1, we
      studied regulation of the gene by transcription factors and epigenetic factors in
      the intestine. To investigate this question, we used a fractionation method to
      separate mature enterocytes from crypt cells and analyzed gene expression.
      Transcription factors HNF1a and HNF4a activate transcription of the Slc6a19 gene
      in villus enterocytes, whereas high levels of SOX9 repress expression in the
      crypts. CpG dinucleotides in the proximal promoter were highly methylated in the
      crypt and fully de-methylated in the villus. Furthermore, histone modification
      H3K27Ac, indicating an active promoter, was prevalent in villus cells but barely
      detectable in crypt cells. The results suggest that Slc6a19 expression in the
      intestine is regulated at three different levels involving promoter methylation,
      histone modification, and opposing transcription factors. 

PMID- 24121512
TI  - A substrate access tunnel in the cytosolic domain is not an essential feature of
      the solute carrier 4 (SLC4) family of bicarbonate transporters.
AB  - Anion exchanger 1 (AE1; Band 3; SLC4A1) is the founding member of the solute
      carrier 4 (SLC4) family of bicarbonate transporters that includes
      chloride/bicarbonate AEs and Na(+)-bicarbonate co-transporters (NBCs). These
      membrane proteins consist of an amino-terminal cytosolic domain involved in
      protein interactions and a carboxyl-terminal membrane domain that carries out the
      transport function. Mutation of a conserved arginine residue (R298S) in the
      cytosolic domain of NBCe1 (SLC4A4) is linked to proximal renal tubular acidosis
      and results in impaired transport function, suggesting that the cytosolic domain
      plays a role in substrate permeation. Introduction of single and double mutations
      at the equivalent arginine (Arg(283)) and at an interacting glutamate (Glu(85))
      in the cytosolic domain of human AE1 (cdAE1) had no effect on the cell surface
      expression or the transport activity of AE1 expressed in HEK-293 cells. In
      addition, the membrane domain of AE1 (mdAE1) efficiently mediated anion
      transport. A 2.1-A resolution crystal structure of cdDelta54AE1 (residues 55-356
      of cdAE1) lacking the amino-terminal and carboxyl-terminal disordered regions,
      produced at physiological pH, revealed an extensive hydrogen-bonded network
      involving Arg(283) and Glu(85). Mutations at these residues affected the pH
      dependent conformational changes and stability of cdDelta54AE1. As these
      structural alterations did not impair functional expression of AE1, the cytosolic
      and membrane domains operate independently. A substrate access tunnel within the
      cytosolic domain is not present in AE1 and therefore is not an essential feature
      of the SLC4 family of bicarbonate transporters. 

PMID- 24121514
TI  - Elastin degradation by cathepsin V requires two exosites.
AB  - Cathepsin V is a highly effective elastase and has been implicated in
      physiological and pathological extracellular matrix degradation. However, its
      mechanism of action remains elusive. Whereas human cathepsin V exhibits a potent
      elastolytic activity, the structurally homologous cathepsin L, which shares a 78%
      amino acid sequence, has only a minimal proteolytic activity toward insoluble
      elastin. This suggests that there are distinct structural domains that play an
      important role in elastinolysis. In this study, a total of 11 chimeras of
      cathepsins V and L were generated to identify elastin-binding domains in
      cathepsin V. Evaluation of these chimeras revealed two exosites contributing to
      the elastolytic activity of cathepsin V that are distant from the active cleft of
      the protease and are located in surface loop regions. Replacement of exosite 1 or
      2 with analogous residues from cathepsin L led to a 75 and 43% loss in the
      elastolytic activity, respectively. Replacement of both exosites yielded a non
      elastase variant similar to that of cathepsin L. Identification of these exosites
      may contribute to the design of inhibitors that will only affect the elastolytic
      activity of cysteine cathepsins without interfering with other physiological
      protease functions. 

PMID- 24121515
TI  - Mesostructural Bi-Mo-O catalyst: correct structure leading to high performance.
AB  - Structure-activity relationship has been one of the main topics of research on
      catalysts all the time. Component and structure are the two moieties governing
      the performance of solid materials as catalysts. Multicomponent bismuth
      molybdates are well known catalysts for propene oxidation but pure crystalline
      phases of bismuth molybdate are inactive for the reaction. We have designed
      mesostructural Bi-Mo-O catalyst with pure bismuth molybdate nanocrystals attached
      to molybdenum oxide nanobelts and found it is a high performance catalyst for the
      reaction, though the two domains themselves are inactive. The strongly expitaxial
      interaction between the two domains causes the lattice shrinkage and distortion
      of the bismuth molybdate nanocrystals and extremely promotes their catalytic
      activity toward propene oxidation while keeping high selectivity at the same
      time. The results are instructive for design of nano oxide catalysts with
      mesostructures leading to high performance. 

PMID- 24121513
TI  - The RHOX homeodomain proteins regulate the expression of insulin and other
      metabolic regulators in the testis.
AB  - Defects in cellular metabolism have been widely implicated in causing male
      infertility, but there has been little progress in understanding the underlying
      mechanism. Here we report that several key metabolism genes are regulated in the
      testis by Rhox5, the founding member of a large X-linked homeobox gene cluster.
      Among these Rhox5-regulated genes are insulin 2 (Ins2), resistin (Retn), and
      adiponectin (Adipoq), all of which encode secreted proteins that have profound
      and wide-ranging effects on cellular metabolism. The ability of Rhox5 to regulate
      their levels in the testis has the potential to dictate metabolism locally in
      this organ, given the existence of the blood-testes barrier. We demonstrate that
      Ins2 is a direct target of Rhox5 in Sertoli cells, and we show that this
      regulation is physiologically significant, because Rhox5-null mice fail to up
      regulate Ins2 expression during the first wave of spermatogenesis and have
      insulin-signaling defects. We identify other Rhox family members that induce Ins2
      transcription, define protein domains and homeodomain amino acid residues crucial
      for this property, and demonstrate that this regulation is conserved. Rhox5-null
      mice also exhibit altered expression of other metabolism genes, including those
      encoding the master transcriptional regulators of metabolism, PPARG and PPARGC1A,
      as well as SCD1, the rate-limiting enzyme for fatty acid metabolism. These
      results, coupled with the known roles of RHOX5 and its target metabolism genes in
      spermatogenesis in vivo, lead us to propose a model in which RHOX5 is a central
      transcription factor that promotes the survival of male germ cells via its
      effects on cellular metabolism. 

PMID- 24121516
TI  - Evaluating minimalist mimics by exploring key orientations on secondary
      structures (EKOS).
AB  - Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not
      peptide polyamides) can be referred to as minimalist mimics. Accessible
      conformations of these scaffolds may overlay with secondary structures giving,
      for example, "minimalist helical mimics". It is difficult for researchers who
      want to apply minimalist mimics to decide which one to use because there is no
      widely accepted protocol for calibrating how closely these compounds mimic
      secondary structures. Moreover, it is also difficult for potential practitioners
      to evaluate which ideal minimalist helical mimics are preferred for a particular
      set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains
      in orientations that best resemble an ideal alpha-helix, and is a different mimic
      required for a i, i + 3, i + 7 helical combination? This article describes a
      protocol for fitting each member of an array of accessible scaffold conformations
      on secondary structures. The protocol involves: (i) use quenched molecular
      dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low
      energy conformers of the mimics; (ii) representation of each of these as a set of
      Calpha and Cbeta coordinates corresponding to three amino acid side-chains
      displayed by the scaffolds; (iii) similar representation of each combination of
      three side-chains in each ideal secondary structure as a set of Calpha and Cbeta
      coordinates corresponding to three amino acid side-chains displayed by the
      scaffolds; and, (iv) overlay Calpha and Cbeta coordinates of all the conformers
      on all the sets of side-chain "triads" in the ideal secondary structures and
      express the goodness of fit in terms of root mean squared deviation (RMSD, A) for
      each overlay. We refer to this process as Exploring Key Orientations on Secondary
      structures (EKOS). Application of this procedure reveals the relative bias of a
      scaffold to overlay on different secondary structures, the "side-chain
      correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and
      the energy of this state relative to the minimum located. This protocol was
      tested on some of the most widely cited minimalist alpha-helical mimics (1-8 in
      the text). The data obtained indicates several of these compounds preferentially
      exist in conformations that resemble other secondary structures as well as alpha
      helices, and many of the alpha-helical conformations have unexpected side-chain
      correspondences. These observations imply the featured minimalist mimics have
      more scope for disrupting PPI interfaces than previously anticipated. Finally,
      the same simulation method was used to match preferred conformations of
      minimalist mimics with actual protein/peptide structures at interfaces providing
      quantitative comparisons of predicted fits of the test mimics at protein-protein
      interaction sites. 

PMID- 24121517
TI  - An improved and robust DNA immunization method to develop antibodies against
      extracellular loops of multi-transmembrane proteins.
AB  - Multi-transmembrane proteins are especially difficult targets for antibody
      generation largely due to the challenge of producing a protein that maintains its
      native conformation in the absence of a stabilizing membrane. Here, we describe
      an immunization strategy that successfully resulted in the identification of
      monoclonal antibodies that bind specifically to extracellular epitopes of a 12
      transmembrane protein, multi-drug resistant protein 4 (MRP4). These monoclonal
      antibodies were developed following hydrodynamic tail vein immunization with a
      cytomegalovirus (CMV) promoter-based plasmid expressing MRP4 cDNA and were
      characterized by flow cytometry. As expected, the use of the immune modulators
      fetal liver tyrosine kinase 3 ligand (Flt3L) and granulocyte-macrophage colony
      stimulating factor positively enhanced the immune response against MRP4. Imaging
      studies using CMV-based plasmids expressing luciferase showed that the in vivo
      half-life of the target antigen was less than 48 h using CMV-based plasmids, thus
      necessitating frequent boosting with DNA to achieve an adequate immune response.
      We also describe a comparison of plasmids, which contained MRP4 cDNA with either
      the CMV or CAG promoters, used for immunizations. The observed luciferase
      activity in this comparison demonstrated that the CAG promoter-containing plasmid
      pCAGGS induced prolonged constitutive expression of MRP4 and an increased anti
      MRP4 specific immune response even when the plasmid was injected less frequently.
      The method described here is one that can be broadly applicable as a general
      immunization strategy to develop antibodies against multi-transmembrane proteins,
      as well as target antigens that are difficult to express or purify in native and
      functionally active conformation.

PMID- 24121518
TI  - Could MM-GBSA be accurate enough for calculation of absolute protein/ligand
      binding free energies?
AB  - Implicit solvation methods such as MM-GBSA, when applied to evaluating
      protein/ligand binding free energies, are widely believed to be accurate only for
      the estimation of relative binding free energies for a congeneric series of
      ligands. In this work, we show that the MM-GBSA flavor of Prime 3.0, VSGB-2.0,
      with a variable dielectric model and a novel energy function, could be
      approaching the accuracy required for evaluating absolute binding free energies,
      albeit, through a linear regression fit. The data-set used for validation
      includes 106 protein-ligand complexes that were carefully selected to control for
      variability in the affinity data as well as error in the modeled complexes.
      Through systematic analysis, we also quantify the degradation in the R(2) of fit
      between experimental and calculated values with either greater variability in the
      affinity data or an increase in error in the modeled protein/ligand complexes.
      Limitations for its application in drug discovery are discussed along with the
      identification of areas for future development. 

PMID- 24121519
TI  - Broadband solar absorption enhancement via periodic nanostructuring of
      electrodes.
AB  - Solution processed colloidal quantum dot (CQD) solar cells have great potential
      for large area low-cost photovoltaics. However, light utilization remains low
      mainly due to the tradeoff between small carrier transport lengths and longer
      infrared photon absorption lengths. Here, we demonstrate a bottom-illuminated
      periodic nanostructured CQD solar cell that enhances broadband absorption without
      compromising charge extraction efficiency of the device. We use finite difference
      time domain (FDTD) simulations to study the nanostructure for implementation in a
      realistic device and then build proof-of-concept nanostructured solar cells,
      which exhibit a broadband absorption enhancement over the wavelength range of
      lambda = 600 to 1,100 nm, leading to a 31% improvement in overall short-circuit
      current density compared to a planar device containing an approximately equal
      volume of active material. Remarkably, the improved current density is achieved
      using a light-absorber volume less than half that typically used in the best
      planar devices.

PMID- 24121520
TI  - Tailoring reach-to-grasp to intended action: the role of motor practice.
AB  - Motor learning results from repeated exposure to the same movement and allows a
      mover to increase movement optimality. Typically, this has only been considered
      in single-step movements. In sequential movements, an initial reach movement is
      tailored to the demands of the onward movement. However, the exact role of motor
      practice in the tailoring to onward task demands is unknown. Eighteen adults
      performed blocks of 15 movements; each movement consisted of a reach phase and an
      onward phase (the object was placed in a tight-fitting hole, placed in a loose
      fitting hole or thrown). Simple practice effects were seen; for the reach phase,
      the amount of time spent decelerating decreased over trials, and for the onward
      phase, the accuracy of the place/throw movements increased over trials.
      Furthermore, approximately 30 % of variance in the practice effect of the onward
      phase could be explained by the practice effect in the reach phase. Therefore, we
      suggest that the changes in the reach phase are directly linked to the changes in
      the efficiency of action and that this is necessary but not sufficient for
      explaining the calibration of the onward action.

PMID- 24121521
TI  - Unconstrained reaching modulates eye-hand coupling.
AB  - Eye-hand coordination is a crucial element of goal-directed movements. However,
      few studies have looked at the extent to which unconstrained movements of the
      eyes and hand made to targets influence each other. We studied human participants
      who moved either their eyes or both their eyes and hand to one of three static or
      flashed targets presented in 3D space. The eyes were directed, and hand was
      located at a common start position on either the right or left side of the body.
      We found that the velocity and scatter of memory-guided saccades (flashed
      targets) differed significantly when produced in combination with a reaching
      movement than when produced alone. Specifically, when accompanied by a reach,
      peak saccadic velocities were lower than when the eye moved alone. Peak saccade
      velocities, as well as latencies, were also highly correlated with those for
      reaching movements, especially for the briefly flashed targets compared to the
      continuous visible target. The scatter of saccade endpoints was greater when the
      saccades were produced with the reaching movement than when produced without, and
      the size of the scatter for both saccades and reaches was weakly correlated.
      These findings suggest that the saccades and reaches made to 3D targets are
      weakly to moderately coupled both temporally and spatially and that this is
      partly the result of the arm movement influencing the eye movement. Taken
      together, this study provides further evidence that the oculomotor and arm motor
      systems interact above and beyond any common target representations shared by the
      two motor systems.

PMID- 24121522
TI  - Bingel-Hirsch monoadducts of TiSc2N@Ih-C80versus Sc3N@Ih-C80: reactivity
      improvement via internal metal atom substitution.
AB  - The first Bingel-Hirsch reaction of TiSc2N@Ih-C80 afforded two unconventional
      singly bonded monoadducts, revealing the dramatically improved reactivity
      compared to Sc3N@Ih-C80 and obvious change in the addition pattern. 

PMID- 24121524
TI  - Association mapping of six yield-related traits in rapeseed (Brassica napus L.).
AB  - Yield is one of the most important traits for rapeseed (Brassica napus L.)
      breeding, but its genetic basis remains largely ambiguous. Association mapping
      has provided a robust approach to understand the genetic basis of complex
      agronomic traits in crops. In this study, a panel of 192 inbred lines of B. napus
      from all over the world was genotyped using 451 single-locus microsatellite
      markers and 740 amplified fragment length polymorphism markers. Six yield-related
      traits of these inbred lines were investigated in three consecutive years with
      three replications, and genome-wide association studies were conducted for these
      six traits. Using the model controlling both population structure and relative
      kinship (Q + K), a total of 43 associations (P < 0.001) were detected using the
      means of the six yield-related traits across 3 years, with two to fourteen
      markers associated with individual traits. Among these, 18 markers were
      repeatedly detected in at least 2 years, and 12 markers were located within or
      close to QTLs identified in previous studies. Six markers commonly associated
      with correlated traits. Conditional association analysis indicated that five of
      the associations between markers and correlated traits are caused by one QTL with
      pleiotropic effects, and the remaining association is caused by linked but
      independent QTLs. The combination of favorable alleles of multiple associated
      markers significantly enhances trait performance, illustrating a great potential
      of utilization of the associations in rapeseed breeding programs.

PMID- 24121523
TI  - TPMT genetic variants are associated with increased rejection with azathioprine
      use in heart transplantation.
AB  - OBJECTIVES: Azathioprine (AZA) is an important immunosuppressant drug used in
      heart transplantation (HTX). Consensus guidelines recommend that patients with
      thiopurine S-methyltransferase (TPMT) genetic variants be started on lower AZA
      dose because of higher active metabolite levels and risk of adverse events.
      However, in-vitro lymphocyte proliferation assays performed in participants with
      inactive TPMT alleles have suggested that AZA use may result in decreased
      immunosuppressant efficacy as compared with wild-type (WT) individuals. The
      objective of this study was therefore to determine the effect of TPMT genetic
      variation on AZA efficacy or prevention of rejection in HTX recipients treated
      with AZA. PARTICIPANTS AND METHODS: We genotyped 93 HTX recipients treated with
      AZA and measured erythrocyte TPMT enzyme activity. Acute rejection was monitored
      by routine endomyocardial biopsies. RESULTS: There were 83 WT and 10 heterozygote
      (HZ) HTX recipients. TPMT activity level was lower in HZ compared with WT (13.1+/
      2.8 vs. 21+/-4.5 U/ml red blood cell, P<0.001). Despite similar AZA dose, HZ
      developed severe rejection earlier (P<0.001), and the total rejection score was
      higher (P=0.02) than WT. AZA was discontinued more frequently in HZ (P=0.01)
      because of rejection. The incidence of leukopenia was similar between the groups
      (40 vs. 43%, P=1.0). CONCLUSION: HTX recipients with TPMT genetic variant alleles
      who are treated with AZA develop acute rejection earlier, more frequently, and of
      greater severity. These patients, despite having lower TPMT enzymatic activity,
      should be monitored carefully for possible increased risk of acute rejection.

PMID- 24121525
TI  - Visualizing the effects of a positive early experience, tactile stimulation, on
      dendritic morphology and synaptic connectivity with Golgi-cox staining.
AB  - To generate longer-term changes in behavior, experiences must be producing stable
      changes in neuronal morphology and synaptic connectivity. Tactile stimulation is
      a positive early experience that mimics maternal licking and grooming in the rat.
      Exposing rat pups to this positive experience can be completed easily and cost
      effectively by using highly accessible materials such as a household duster.
      Using a cross-litter design, pups are either stroked or left undisturbed, for 15
      min, three times per day throughout the perinatal period. To measure the
      neuroplastic changes related to this positive early experience, Golgi-Cox
      staining of brain tissue is utilized. Owing to the fact that Golgi-Cox
      impregnation stains a discrete number of neurons rather than all of the cells,
      staining of the rodent brain with Golgi-Cox solution permits the visualization of
      entire neuronal elements, including the cell body, dendrites, axons, and
      dendritic spines. The staining procedure is carried out over several days and
      requires that the researcher pay close attention to detail. However, once
      staining is completed, the entire brain has been impregnated and can be preserved
      indefinitely for ongoing analysis. Therefore, Golgi-Cox staining is a valuable
      resource for studying experience-dependent plasticity. 

PMID- 24121527
TI  - Flexible transparent conductive materials based on silver nanowire networks: a
      review.
AB  - The class of materials combining high electrical or thermal conductivity, optical
      transparency and flexibility is crucial for the development of many future
      electronic and optoelectronic devices. Silver nanowire networks show very
      promising results and represent a viable alternative to the commonly used, scarce
      and brittle indium tin oxide. The science and technology research of such
      networks are reviewed to provide a better understanding of the physical and
      chemical properties of this nanowire-based material while opening attractive new
      applications. 

PMID- 24121528
TI  - A structural and dynamic investigation of the inhibition of catalase by nitric
      oxide.
AB  - Determining the chemical and structural modifications occurring within a protein
      during fundamental processes such as ligand or substrate binding is essential to
      building up a complete picture of biological function. Currently, significant
      unanswered questions relate to the way in which protein structural dynamics fit
      within the structure-function relationship and to the functional role, if any, of
      bound water molecules in the active site. Addressing these questions requires a
      multidisciplinary approach and complementary experimental techniques that, in
      combination, enhance our understanding of the complexities of protein chemistry.
      We exemplify this philosophy by applying both physical and biological approaches
      to investigate the active site chemistry that contributes to the inhibition of
      the Corynebacterium glutamicum catalase enzyme by nitric oxide. Ultrafast two
      dimensional infrared spectroscopy (2D-IR) experiments exploit the NO ligand as a
      local probe of the active site molecular environment and shows that catalase
      displays a dynamically-restricted, 'tight,' structure. X-ray crystallography
      studies of C. glutamicum catalase confirm the presence of a conserved chain of
      hydrogen-bonded bound water molecules that link the NO ligand and the protein
      scaffold. This combination of bound water and restricted dynamics stands in stark
      contrast to other haem proteins, such as myoglobin, that exhibit ligand transport
      functionality despite the presence of a similar distal architecture in close
      proximity to the ligand. We conclude not only that the bound water molecules in
      the catalase active site play an important role in molecular recognition of NO
      but also may be part of the mechanistic operation of this important enzyme. 

PMID- 24121526
TI  - Cytonemes are required for the establishment of a normal Hedgehog morphogen
      gradient in Drosophila epithelia.
AB  - Hedgehog (Hh) signalling is important in development, stem cell biology and
      disease. In a variety of tissues, Hh acts as a morphogen to regulate growth and
      cell fate specification. Several hypotheses have been proposed to explain
      morphogen movement, one of which is transport along filopodia-like protrusions
      called cytonemes. Here, we analyse the mechanism underlying Hh movement in the
      wing disc and the abdominal epidermis of Drosophila melanogaster. We show that,
      in both epithelia, cells generate cytonemes in regions of Hh signalling. These
      protrusions are actin-based and span several cell diameters. Various Hh
      signalling components localize to cytonemes, as well as to punctate structures
      that move along cytonemes and are probably exovesicles. Using in vivo imaging, we
      show that cytonemes are dynamic structures and that Hh gradient establishment
      correlates with cytoneme formation in space and time. Indeed, mutant conditions
      that affect cytoneme formation reduce both cytoneme length and Hh gradient
      length. Our results suggest that cytoneme-mediated Hh transport is the
      mechanistic basis for Hh gradient formation. 

PMID- 24121529
TI  - Association between a composite score of pain sensitivity and clinical parameters
      in low-back pain.
AB  - BACKGROUND AND AIMS: A limited number of quantitative sensory pain tests (QST)
      were selected on the basis of ease of application and interpretation in a
      clinical setting. QST results were summarized as a composite score on a scale of
      0 to 4 that was deemed to facilitate clinical interpretation. The QST set was
      used to investigate differences in pain sensitivity between low-back pain (LBP)
      subgroups and was correlated with important clinical parameters. MATERIALS AND
      METHODS: A total of 198 LBP patients and 44 controls were recruited and data were
      collected on: LBP intensity and duration, improvement in LBP, functional status,
      psychological profile, quality of life, and current work situation. QST consisted
      of pressure-pain threshold of the infraspinatus muscle, pain intensity with
      sustained mechanical pressure on the thumb nailbed, conditioned pain modulation,
      and pain tolerance assessed by cold-pressor test. RESULTS: Chronic, but not acute
      LBP patients scored significantly higher on the composite score of pain
      sensitivity than controls. A weak linear correlation between the composite score
      of pain sensitivity and intensity of clinical LBP and disability was found. A
      contingency was found between a high pain sensitivity (dichotomized composite
      score of pain sensitivity) and the lack of improvement in LBP. Pain sensitivity
      did not correlate with LBP duration, psychological profile, or sick leave.
      CONCLUSIONS: Pain sensitivity may be important for the prognosis of LBP, but QST
      is not currently part of routine clinical examination of LBP patients. The
      selected set of pain tests and the composite score of pain sensitivity could
      serve as a clinically applicable QST procedure in the examination of LBP.

PMID- 24121530
TI  - Characterization of pain in fabry disease.
AB  - OBJECTIVE: To give a detailed characterization of pain in a large cohort of
      patients with Fabry disease. PATIENTS AND METHODS: In this single-center,
      retrospective study we performed a detailed analysis of pain prevalence and
      characteristics of 132 patients with Fabry disease. Data were obtained by
      screening all medical records and using standardized extraction forms. Missing
      data were completed by telephone interviews. RESULTS: We show that men and women
      with Fabry disease frequently experience pain, mostly starting in early
      childhood. Pain is typically episodic with pain attacks being the predominant
      phenotype. The most frequent localization is in the distal extremities, the most
      often named pain quality is "burning." Fabry pain is triggerable by physical
      activity and thermal stimuli and improves over time. Frequently used acute pain
      medication consists of nonsteroidal antirheumatics and nonopioid analgesics. Long
      term medications such as drugs used to treat neuropathic pain syndromes are
      rarely taken by Fabry patients. CONCLUSIONS: Pain in Fabry disease affects both
      sexes and has a complex phenotype that requires comprehensive assessment. Current
      pain questionnaires fail to cover the entire scope of Fabry pain. Although
      basically neuropathic, some types of Fabry pain may respond to nonsteroidal
      antirheumatics and nonopioid analgesics.

PMID- 24121531
TI  - Complexation between Cu(II) and curcumin in the presence of two different
      segments of amyloid beta.
AB  - The natural product curcumin has been shown to play a role in preventing Abeta
      amyloid fibril formation. This role could include chelation of transition metal
      ions such as Cu(2+), known to accelerate amyloid aggregation, and/or curcumin
      binding directly to the Abeta protein. To investigate these different roles,
      curcumin complexation to Cu(2+) was investigated in the presence and absence of
      two different segments of the Abeta protein including the copper-binding (Abeta6
      14) and curcumin-binding (Abeta14-23) domains. Absorbance and fluorescence
      spectroscopy in 90% water/10% methanol solutions showed that curcumin can bind
      Cu(2+) to some extent in the presence of both segments despite strong peptide-ion
      interactions. Estimated Cu(2+)-curcumin binding affinities in the absence
      (1.6*10(5)M(-1)) and presence (7.9*10(4)M(-1)) of the peptide provide
      quantitative support for this Cu(2+) chelation role. With the Abeta14-23 segment,
      the curcumin simultaneously binds to Cu(2+) and the peptide, demonstrating that
      it can play multiple roles in the prevention of amyloid formation. The
      stabilities of ternary peptide-Cu(2+)-curcumin complexes were evaluated using ESI
      mass spectrometry and support the conclusion that curcumin can act as a weak
      metal ion chelator and also bind directly to the Abeta14-23 peptide segment. 

PMID- 24121532
TI  - Benzannulated N-heterocyclic germylenes and stannylenes with sterically demanding
      N,N'-substituents.
AB  - Four N,N'-disubstituted 1,2-diaminobenzes (1a: R = t-Bu, 1b: R = adamantyl, 1c: R
      = Ph, 1d: R = Dipp) have been prepared and reacted with E[N(SiMe3)2]2 (E = Ge,
      Sn) to give the benzannulated N-heterocyclic germylenes 2a-d and stannylenes 3a
      d. Germylene 2d and stannylenes 3a, 3c and 3d have been characterized by X-ray
      diffraction showing different types of intermolecular interactions in the solid
      state. Deprotonation of 1b with n-BuLi yields the lithium stannyl anion Li[4]
      with an n-Bu group bound to the tin(II) center.

PMID- 24121533
TI  - The variable hydroxamic acid siderophore metabolome of the marine actinomycete
      Salinispora tropica CNB-440.
AB  - The recently sequenced genome of the marine actinomycete Salinispora tropica CNB
      440 revealed a high frequency of gene clusters which code for the biosynthesis of
      known and novel secondary metabolites. Of these metabolites, bioinformatics
      analysis predicted that S. tropica CNB-440 could potentially biosynthesize, as
      high affinity Fe(iii) ligands, siderophores from the hydroxamic acid
      desferrioxamine class (sid1 gene cluster) and the phenolate-thia(oxa)zoli(di)ne
      class (sid2 and sid4 gene clusters). In this work, we have used Ni(ii)-based
      immobilized metal ion affinity chromatography (IMAC) to pre-fractionate the
      hydroxamic acid siderophore metabolome of S. tropica CNB-440 from the secondary
      metabolome, to reveal low abundance siderophores. LC-MS measurements and
      electronic absorption spectra from purified extracts incubated with exogenous
      Fe(iii) revealed eight siderophores from the desferrioxamine class (DFOA2,
      DFOA1a, DFOA1b, DFOB, DFON, DFOD2, DFOE, DFOD1), which included two
      constitutional isomers (DFOA1a, DFOA1b), and one new siderophore (DFON), the
      latter which would require assembly from a combination of 1,5-diaminopentane and
      1,6-diaminohexane as diamine substrates. Three additional species (m/zobs 496.14,
      792.34 and 804.34) with electronic absorption spectra characteristic of complexes
      formed between Fe(iii) and hydroxamic acid-type siderophores were evident under
      some conditions. The signal at m/zobs 792.34 eluted in the hydrophobic region of
      the reverse-phase LC and correlated with a DFOD1 analogue with a C-terminal
      branched chain fatty acid ([M + K(+)](+)m/zcalc 792.35), which has been
      previously identified from marine sediment dwelling Micrococcus luteus KLE1011.
      The S. tropica CNB-440 hydroxamic acid siderophore metabolome was modulated by
      culture conditions (pH 7, 22  degrees C; pH 7, 28  degrees C; pH 9, 28  degrees
      C) designed to simulate the variable marine environment. An increase in
      temperature at constant pH value showed increased levels of DFOA2 and DFOA1, and
      decreased levels of DFOB and DFOE. An increase in pH value at constant
      temperature showed decreased levels of DFOA2 and DFOA1, and increased levels of
      DFOB, DFON and DFOE. These results indicate that the marine adaptation of S.
      tropica CNB-440 could involve its ability to select a suite of siderophores from
      a large number of candidates, which are optimized for the iron microenvironment. 

PMID- 24121534
TI  - Synthesis, characterization and electrochemical properties of iron-zirconia solid
      solution nanoparticles prepared using a sol-gel technique.
AB  - The range of compositions and temperatures at which single-phase tetragonal and
      monoclinic Fe-containing zirconia nanoparticles are stable is reported. Both
      types of iron-doped zirconia particles were synthesized by annealing dried gels
      FexZr1-xO2, with nominal compositions in the range 0 <= x <= 0.15, over the range
      of temperatures between 400  degrees C and 1300  degrees C. Monophasic
      crystalline specimens of Fe-ZrO2 solid solutions were characterized by different
      techniques including X-ray powder diffraction (XRD), infrared and Raman
      spectroscopies (IR and Raman), and transmission electron microscopy (TEM). Energy
      gaps were estimated from diffuse reflectance ultraviolet-visible spectra (DRUV
      Vis) and compared with those obtained from electrochemical data. Upon increasing
      the amount of iron in both types of iron-containing zirconia-based structures the
      energy gaps slightly lowered. The electrochemical properties of those solid
      solutions obtained using the voltammetry of microparticles (VPM) technique
      indicated the presence of a small portion of iron as Fe(2+) in both types of
      crystalline Fe-doped ZrO2. Electrochemical data suggest that the monoclinic solid
      solutions provide a particularly high accessibility for promoting catalytic
      processes such as electrochemical oxygen reduction. 

PMID- 24121535
TI  - Detailed kinetic analysis of the interaction between the FOXO4-DNA-binding domain
      and DNA.
AB  - The FOXO forkhead transcription factors are potent transcriptional activators
      involved in a wide range of key biological processes. In this work, the real-time
      kinetics of the interaction between the FOXO4-DNA binding domain (FOXO4-DBD) and
      the DNA was studied by using surface plasmon resonance (SPR). SPR analysis
      revealed that the interaction between FOXO4-DBD and the double stranded DNA
      containing either the insulin-responsive or the Daf-16 family member-binding
      element is preferably described by using a conformational change model which
      suggests a structural change of FOXO4-DBD upon binding to the DNA. This was
      further confirmed by using the time-resolved tryptophan fluorescence anisotropy
      decay measurements which revealed profound reduction of segmental dynamics of
      FOXO4-DBD upon the complex formation. Alanine scanning of amino acid residues
      engaged in polar contacts with the DNA showed that certain non-specific contacts
      with the DNA backbone are very important for both the binding affinity and the
      binding specificity of FOXO4-DBD. 

PMID- 24121536
TI  - Trogocytosis in allogeneic transplants: donor cells take on the recipients
      identity.
AB  - Trogocytosis has been identified as a mechanism of cell communication between
      immune cells. Unlike the more common receptor-ligand signaling, trogocytosis
      results in the transfer of intact and functional surface proteins between cells.
      For example, antigen presenting cells in contact with T cells exchange proteins
      which results in the T-cell acquiring antigen presentation capabilities. This
      allows for the newly activated T cells to stimulate other T cells thus amplifying
      the immune response. We have recently demonstrated that during allogeneic
      hematopoietic stem cell transplantation the donor cells obtain recipient MHC
      class I proteins by trogocytosis. The effect is a donor cell that can masquerade
      as a recipient cells and evade detection by NK cells and macrophages. 

PMID- 24121537
TI  - Case study in designing a research fundamentals curriculum for community health
      workers: a university-community clinic collaboration.
AB  - Community health workers (CHWs) are increasingly incorporated into research
      teams. Training them in research methodology and ethics, while relating these
      themes to a community's characteristics, may help to better integrate these
      health promotion personnel into research teams. An interactive training course on
      research fundamentals for CHWs was designed and implemented jointly by a
      community agency serving a primarily Latino, rural population and an academic
      health center. A focus group of community members and input from community
      leaders comprised a community-based participatory research model to create three
      3-hour interactive training sessions. The resulting curriculum was interactive
      and successfully stimulated dialogue between trainees and academic researchers.
      By choosing course activities that elicited community-specific responses into
      each session's discussion, researchers learned about the community as much as the
      training course educated CHWs about research. The approach is readily adaptable,
      making it useful to other communities where CHWs are part of the health system. 

PMID- 24121538
TI  - Trogocytosis as a mechanistic link between chimerism and prenatal tolerance.
AB  - In utero hematopoietic cellular transplantation (IUHCT) holds great promise for
      the treatment of congenital diseases of cellular dysfunction such as sickle cell
      disease, immunodeficiency disorders and inherited metabolic disorders. However,
      repeated failures in clinical cases of IUHCT that do not involve an
      immunodeficiency disease force a closer examination of the fetal immune system.
      While the mechanisms regulating T cell tolerance have been previously studied,
      the educational mechanisms leading to NK cell tolerance in prenatal chimeras
      remain unknown. As a low level of donor cells (1.8%) is required to induce and
      maintain this tolerance, it is likely that these mechanisms employ indirect host
      donor interaction. This report examines donor-to-host MHC transfer (trogocytosis)
      as an intrinsic mechanism regulating the development and maintenance of NK cell
      tolerance in prenatal chimeras. The findings demonstrate that phenotypically
      tolerant host NK cells express low levels of transferred donor MHC antigens
      during development and later as mature cytotoxic lymphocytes. Further study is
      needed to understand how the cis-recognition of transferred donor MHC ligand
      influences the selection and maintenance of tolerant NK cells in prenatal
      chimeras. 

PMID- 24121540
TI  - Programming stem cells for therapeutic angiogenesis using biodegradable polymeric
      nanoparticles.
AB  - Controlled vascular growth is critical for successful tissue regeneration and
      wound healing, as well as for treating ischemic diseases such as stroke, heart
      attack or peripheral arterial diseases. Direct delivery of angiogenic growth
      factors has the potential to stimulate new blood vessel growth, but is often
      associated with limitations such as lack of targeting and short half-life in
      vivo. Gene therapy offers an alternative approach by delivering genes encoding
      angiogenic factors, but often requires using virus, and is limited by safety
      concerns. Here we describe a recently developed strategy for stimulating vascular
      growth by programming stem cells to overexpress angiogenic factors in situ using
      biodegradable polymeric nanoparticles. Specifically our strategy utilized stem
      cells as delivery vehicles by taking advantage of their ability to migrate toward
      ischemic tissues in vivo. Using the optimized polymeric vectors, adipose-derived
      stem cells were modified to overexpress an angiogenic gene encoding vascular
      endothelial growth factor (VEGF). We described the processes for polymer
      synthesis, nanoparticle formation, transfecting stem cells in vitro, as well as
      methods for validating the efficacy of VEGF-expressing stem cells for promoting
      angiogenesis in a murine hindlimb ischemia model. 

PMID- 24121541
TI  - Thermal/electron irradiation assisted coalescence of Sc3N@C80 fullerene in carbon
      nanotube and evidence of charge transfer between pristine/coalesced fullerenes
      and nanotubes.
AB  - Sc3N@C80 fullerenes are inserted inside carbon nanotubes (CNTs). The results show
      that the thermal stability of Sc3N@C80 fullerenes is around 1200  degrees C for
      the fullerenes resting on the wall of CNTs. Internal fullerenes show stability up
      to 1300  degrees C, which portrays them as one of most stable types of
      fullerenes. Electron irradiation of the peapods at 90 kV leads to the formation
      of capsules inside the CNTs at 5 * 10(9) e nm(-2) electron dosage. This value is
      an order of magnitude higher than the threshold of electron-induced damage in C60
      molecules. Electron energy loss spectroscopy confirms the presence of Sc atoms in
      capsules. Encapsulation of fullerenes and capsule formation changes the oxidation
      state of Sc atoms from +2.5 towards +3. This is an evidence of charge transfer
      between the fullerene/capsule cage and CNT walls. 

PMID- 24121539
TI  - Noisy silence: non-coding RNA and heterochromatin formation at repetitive
      elements.
AB  - A significant fraction of eukaryotic genomes comprises repetitive sequences,
      including rRNA genes, centromeres, telomeres, and retrotransposons. Repetitive
      elements are hotspots for recombination and represent a serious challenge for
      genome integrity. Maintaining these repeated elements in a compact
      heterochromatic structure suppresses recombination and unwanted mutagenic
      transposition, and is therefore indispensable for genomic stability.
      Paradoxically, repetitive elements are not transcriptionally inert, but produce
      RNA that has important functions in regulating and reinforcing the
      heterochromatic state. Here, we review the role of non-coding RNA (ncRNA) in
      recruiting chromatin-modifying enzymes to repetitive genomic loci to establish a
      repressive chromatin structure that safeguards chromosome integrity and genome
      stability. 

PMID- 24121543
TI  - Erythrose revealed as furanose forms.
AB  - A non-conventional vaporization method, using laser ablation of solid NaCl doped
      with d-erythrose, has been used to bring this sugar into the gas phase for
      rotational study. The jet cooled rotational spectrum of this C4 monosaccharide
      reveals the existence of two furanose forms, one alpha envelope and one beta
      twist. Cooperative hydrogen bond networks and the anomeric effect have been found
      to be the main stabilization factors of the detected structures. 

PMID- 24121544
TI  - Applying a multi-criteria genetic algorithm framework for brownfield reuse
      optimization: improving redevelopment options based on stakeholder preferences.
AB  - The reuse of underused or abandoned contaminated land, so-called brownfields, is
      increasingly seen as an important means for reducing the consumption of land and
      natural resources. Many existing decision support systems are not appropriate
      because they focus mainly on economic aspects, while neglecting sustainability
      issues. To fill this gap, we present a framework for spatially explicit,
      integrated planning and assessment of brownfield redevelopment options. A multi
      criteria genetic algorithm allows us to determine optimal land use configurations
      with respect to assessment criteria and given constraints on the composition of
      land use classes, according to, e.g., stakeholder preferences. Assessment
      criteria include sustainability indicators as well as economic aspects, including
      remediation costs and land value. The framework is applied to a case study of a
      former military site near Potsdam, Germany. Emphasis is placed on the trade-off
      between possibly conflicting objectives (e.g., economic goals versus the need for
      sustainable development in the regional context of the brownfield site), which
      may represent different perspectives of involved stakeholders. The economic
      analysis reveals the trade-off between the increase in land value due to reuse
      and the costs for remediation required to make reuse possible. We identify
      various reuse options, which perform similarly well although they exhibit
      different land use patterns. High-cost high-value options dominated by
      residential land use and low-cost low-value options with less sensitive land use
      types may perform equally well economically. The results of the integrated
      analysis show that the quantitative integration of sustainability may change
      optimal land use patterns considerably. 

PMID- 24121542
TI  - Impact of methionine oxidation as an initial event on the pathway of human prion
      protein conversion.
AB  - Prion diseases comprise a group of fatal neurodegenerative disorders
      characterized by the autocatalytic conversion of the cellular prion protein
      PrP(C) into the infectious misfolded isoform PrP(Sc). Increasing evidence
      supports a specific role of oxidative stress in the onset of pathogenesis.
      Although the associated molecular mechanisms remain to be elucidated in detail,
      several studies currently suggest that methionine oxidation already detected in
      misfolded PrP(Sc) destabilizes the native PrP fold as an early event in the
      conversion pathway. To obtain more insights about the specific impact of surface
      exposed methionine residues on the oxidative-induced conversion of human PrP we
      designed, produced, and comparatively investigated two new pseudosulfoxidation
      mutants of human PrP 121-231 that comprises the well-folded C-terminal domain.
      Applying circular dichroism spectroscopy and dynamic light scattering techniques
      we showed that pseudosulfoxidation of all surface exposed Met residues formed a
      monomeric molten globule-like species with striking similarities to misfolding
      intermediates recently reported by other groups. However, individual
      pseudosulfoxidation at the polymorphic M129 site did not significantly contribute
      to the structural destabilization. Further metal-induced oxidation of the partly
      unfolded pseudosulfoxidation mutant resulted in the formation of an oligomeric
      state that shares a comparable size and stability with PrP oligomers detected
      after the application of different other triggers for structural conversion,
      indicating a generic misfolding pathway of PrP. The obtained results highlight
      the specific importance of methionine oxidation at surface exposed residues for
      PrP misfolding, strongly supporting the hypothesis that increased oxidative
      stress could be one causative event for sporadic prion diseases and other
      neurodegenerative disorders. 

PMID- 24121545
TI  - Effect of ash circulation in gasification melting system on concentration and
      leachability of lead in melting furnace fly ash.
AB  - In some gasification-melting plants, generated melting furnace fly ash is
      returned back to the melting furnace for converting the ash to slag. This study
      investigated the effect of such ash circulation in the gasification-melting
      system on the concentration and leachability of lead in the melting furnace fly
      ash. The ash circulation in the melting process was simulated by a thermodynamic
      calculation, and an elemental analysis and leaching tests were performed on a
      melting furnace fly ash sample collected from the gasification-melting plant with
      the ash circulation. It was found that by the ash circulation in the gasification
      melting, lead was highly concentrated in the melting furnace fly ash to the level
      equal to the fly ash from the ash-melting process. The thermodynamic calculation
      predicted that the lead volatilization by the chlorination is promoted by the ash
      circulation resulting in the high lead concentration. In addition, the lead
      extraction from the melting furnace fly ash into a NaOH solution was also
      enhanced by the ash circulation, and over 90% of lead in the fly ash was
      extracted in 5 min when using 0.5 mol l(-1) NaOH solution with L/S ratio of 10 at
      100  degrees C. Based on the results, a combination of the gasification-melting
      with the ash circulation and the NaOH leaching method is proposed for the high
      efficient lead recovery. 

PMID- 24121546
TI  - Phosphate sludge: thermal transformation and use as lightweight aggregate
      material.
AB  - Phosphate sludge generated from beneficiation plants of Moroccan phosphate rocks
      was investigated at 900-1200  degrees C by X-ray diffraction, scanning electron
      microscopy, thermal analysis and Fourier-transform infrared spectroscopy.
      Mixtures of the phosphate sludge and a swelling clay (up to 30 wt.%) were
      investigated and their properties (shrinkage, density, water absorption and
      compressive strength) were measured as a function of temperature and clay
      addition. The results showed that gehlenite neoformed from lime of decomposed
      carbonates and breakdown products of clay minerals and that fluorapatite
      (original mineral) resisted heating until fusion. The measured properties were
      mainly controlled by temperature, and the effect of clay addition was less
      regular, except for water absorption. Considering the mixtures densities (1.44
      3.02 g/cm(3)), lightweight agglomerates can be produced at 900 or 1100  degrees
      C, but their compressive strengths were relatively low (2-4.5 MPa). Based on SiO2
      Al2O3-Fluxes diagram and taking account of the chemical composition of the
      materials used, the production of expanded aggregates requires clay additions as
      high as 80 wt.%.

PMID- 24121547
TI  - Voltage and power-controlled regimes in the progressive unipolar RESET transition
      of HfO2-based RRAM.
AB  - Resistive switching (RS) based on the formation and rupture of conductive
      filament (CF) is promising in novel memory and logic device applications.
      Understanding the physics of RS and the nature of CF is of utmost importance to
      control the performance, variability and reliability of resistive switching
      memory (RRAM). Here, the RESET switching of HfO2-based RRAM was statistically
      investigated in terms of the CF conductance evolution. The RESET usually combines
      an abrupt conductance drop with a progressive phase ending with the complete CF
      rupture. RESET1 and RESET2 events, corresponding to the initial and final phase
      of RESET, are found to be controlled by the voltage and power in the CF,
      respectively. A Monte Carlo simulator based on the thermal dissolution model of
      unipolar RESET reproduces all of the experimental observations. The results
      contribute to an improved physics-based understanding on the switching mechanisms
      and provide additional support to the thermal dissolution model. 

PMID- 24121548
TI  - Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration.
AB  - In order to determine the frequency of microtubule-associated protein tau gene
      (MAPT) mutations and rare variants in CBD, we performed a systematic sequence
      analysis of MAPT coding and 3' untranslated region (3'UTR) in a large cohort of
      autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation
      in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from
      sporadic CBD. On immunoblot, the p.N410H mutation carrier had the same insoluble
      tau profile as seen in CBD. Additionally, tau expression analysis in brain tissue
      found a significant increase in the 4R/3R tau mRNA ratio (P = 0.04), indicating
      that p.N410H disrupts tau isoform homeostasis. Biochemically, recombinant tau
      protein with p.N410H showed a marked increase in tau filament formation compared
      to wild-type tau (P < 0.001), had a 19.2% decrease in rate of microtubule
      assembly (P < 0.05), and a 10.3% reduction in the extent of total microtubule
      polymerization (P < 0.01). Sequence analysis of the complete MAPT 3'UTR in
      autopsy-confirmed CBD cases further identified two rare variants with nominally
      significant association with CBD. An ATC nucleotide insertion ("MAPTv8") was
      found in 4.6% of CBD patients compared to 1.2% of controls (P = 0.031, OR =
      3.71), and rs186977284 in 4.6% CBD patients, but only 0.9% of controls (P = 0.04,
      OR = 3.58). Rs186977284 was also present in 2.7% of a large cohort of autopsy
      confirmed PSP patients (N = 566) and only 0.9% of an additional control series (P
      = 0.034, OR = 3.08), extending the association to PSP. Our findings show that
      mutations in MAPT can cause CBD and MAPT non-coding variants may increase the
      risk of complex 4R tauopathies.

PMID- 24121549
TI  - pIMP-PH114 carrying bla IMP-4 in a Klebsiella pneumoniae strain is closely
      related to other multidrug-resistant IncA/C2 plasmids.
AB  - The IncA/C plasmids are broad host-range vehicles which have been associated with
      wide dissemination of CMY-2 among Enterobacteriaceae of human and animal origins.
      Acquired metallo-beta-lactamases (MBLs) such as the IMP-type enzymes are
      increasingly reported in multidrug-resistant Gram-negative bacteria worldwide,
      particularly in Enterobacteriaceae. We described the complete sequence of the
      first IMP-4-encoding IncA/C2 plasmid, pIMP-PH114 (151,885 bp), from a sequence
      type 1 Klebsiella pneumoniae strain that was recovered from a patient who was
      hospitalized in the Philippines. pIMP-PH114 consists of a backbone from the
      IncA/C2 plasmids, with the insertion of a novel Tn21-like class 1 integron
      composite structure (containing the cassette array bla IMP-4-qacG-aacA4-catB3,
      followed by a class C beta-lactamase bla DHA-1 and the mercury resistance operon,
      merRTPCADE) and a sul2-floR encoding region. Phylogenetic analysis of the IncA/C
      repA sequences showed that pIMP-PH114 formed a subgroup with other IncA/C
      plasmids involved in the international spread of CMY-2, TEM-24 and NDM-1.
      Identical bla IMP-4 arrays have been described among different Enterobacteriaceae
      and Acinetobacter spp. in China, Singapore and Australia but the genetic context
      is different. The broad host range of IncA/C plasmids may have facilitated
      dissemination of the bla IMP-4 arrays among different diverse groups of bacteria.

PMID- 24121550
TI  - Abatement kinetics of 30 sulfonylurea herbicide residues in water by
      photocatalytic treatment with semiconductor materials.
AB  - Sulfonylurea herbicides (SUHs) are a family of environmentally compatible
      herbicides but their high water solubility, moderate to high mobility through the
      soil profile, and slow degradation rate make them potential contaminants of
      groundwater as demonstrated in this paper. The photodegradation of a mixture of
      30 SUHs in aqueous suspensions of semiconductor materials (ZnO and TiO2 in tandem
      with Na2S2O8 as electron acceptor) under artificial light (300-460 nm)
      irradiation was investigated. As expected, the influence of both semiconductors
      on the degradation of SUHs was very significant in all cases. Photocatalytic
      experiments show that the addition of photocatalyst, especially for the
      ZnO/Na2S2O8 system, greatly improves the removal of SUHs compared with photolytic
      tests, significantly increasing the reaction rates. The first-order equation
      (monophasic model) satisfactorily explained the disappearance process although it
      overlooked small residues remaining late in the process. These residues are
      important from an environmental point of view and the Hoerl function (biphasic
      model), was a better predicter of the results obtained. In our conditions, the
      average time required for 90% degradation was about 3 and 30 min for ZnO/Na2S2O8
      and TiO2/Na2S2O8 systems, respectively. 

PMID- 24121551
TI  - Biosensing with microbial fuel cells and artificial neural networks: laboratory
      and field investigations.
AB  - In this study microbial fuel cell-based biosensing was integrated with artificial
      neural networks (ANNs) in laboratory and field testing of water samples.
      Inoculation revealed two types of anode-respiring bacteria (ARB) induction
      profiles, a relatively slow gradual profile and a faster profile that was
      preceded by a significant lag time. During laboratory testing, the MFCs generated
      well-organized normally distributed profiles but during field experiments the
      peaks had irregular shapes and were smaller in magnitude. Generally, the COD
      concentration correlated better with peak area than with peak height. The ANN
      predicted the COD concentration (R(2) = 0.99) with one layer of hidden neurons
      and for concentrations as low as 5 mg acetate-COD/L. Adding 50 mM of 2
      bromoethanesulfonate amplified the electrical signals when glucose was the
      substrate. This report is the first to identify two types of ARB induction
      profiles and to demonstrate the power of ANNs for interpreting a wide variety of
      electrical response peaks. 

PMID- 24121552
TI  - Metabolic suppression identifies new antibacterial inhibitors under nutrient
      limitation.
AB  - Characterizing new drugs and chemical probes of biological systems is hindered by
      difficulties in identifying the mechanism of action (MOA) of biologically active
      molecules. Here we present a metabolite suppression approach to explore the MOA
      of antibacterial compounds under nutrient restriction. We assembled an array of
      metabolites that can be screened for suppressors of inhibitory molecules.
      Further, we identified inhibitors of Escherichia coli growth under nutrient
      limitation and charted their interactions with our metabolite array. This
      strategy led to the discovery and characterization of three new antibacterial
      compounds, MAC168425, MAC173979 and MAC13772. We showed that MAC168425 interferes
      with glycine metabolism, MAC173979 is a time-dependent inhibitor of p
      aminobenzoic acid biosynthesis and MAC13772 inhibits biotin biosynthesis. We
      conclude that metabolite suppression profiling is an effective approach to focus
      MOA studies on compounds impairing metabolic capabilities. Such bioactives can
      serve as chemical probes of bacterial physiology and as leads for antibacterial
      drug development. 

PMID- 24121553
TI  - Distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway
      crosstalk.
AB  - Spirotryprostatins, an indole alkaloid class of nonribosomal peptides isolated
      from Aspergillus fumigatus, are known for their antimitotic activity in tumor
      cells. Because spirotryprostatins and many other chemically complex spiro-carbon
      bearing natural products exhibit useful biological activities, identifying and
      understanding the mechanism of spiro-carbon biosynthesis is of great interest.
      Here we report a detailed study of spiro-ring formation in spirotryprostatins
      from tryprostatins derived from the fumitremorgin biosynthetic pathway, using
      reactants and products prepared with engineered yeast and fungal strains.
      Unexpectedly, FqzB, an FAD-dependent monooxygenase from the unrelated
      fumiquinazoline biosynthetic pathway, catalyzed spiro-carbon formation in
      spirotryprostatin A via an epoxidation route. Furthermore, FtmG, a cytochrome
      P450 from the fumitremorgin biosynthetic pathway, was determined to catalyze the
      spiro-ring formation in spirotryprostatin B. Our results highlight the versatile
      role of oxygenating enzymes in the biosynthesis of structurally complex natural
      products and indicate that cross-talk of different biosynthetic pathways allows
      product diversification in natural product biosynthesis. 

PMID- 24121555
TI  - Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and
      Ir(III) pyridyl ester complexes as in vitro antiparasitic and antitumor agents.
AB  - New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di
      and tripyridyl ester ligands have been synthesised and characterised using
      analytical and spectroscopic techniques including (1)H, (13)C NMR and infrared
      spectroscopy. Reaction of these polypyridyl ester ligands with either [Ru(p
      cymene)Cl2]2, [Rh(C5Me5)Cl2]2 or [Ir(C5Me5)Cl2]2 dimers yielded the corresponding
      di- or trinuclear organometallic complexes. The polyaromatic ester ligands act as
      monodentate donors to each metal centre and this coordination mode was confirmed
      upon elucidation of the molecular structures for two of the dinuclear complexes.
      The di- and trinuclear PGM complexes synthesized were evaluated for inhibitory
      effects on the human protozoal parasites Plasmodium falciparum strain NF54
      (chloroquine sensitive), Trichomonas vaginalis strain G3 and the human ovarian
      cancer cell lines, A2780 (cisplatin-sensitive) and A2780cisR (cisplatin
      resistant) cell lines. All of the complexes were observed to have moderate to
      high antiplasmodial activities and the compounds with the best activities were
      evaluated for their ability to inhibit formation of synthetic hemozoin in a cell
      free medium. The in vitro antitumor evaluation of these complexes revealed that
      the trinuclear pyridyl ester complexes demonstrated moderate activities against
      the two tumor cell lines and were also less toxic to model non-tumorous cells. 

PMID- 24121556
TI  - Microbial diversity associated with tetrodotoxin production in marine organisms.
AB  - Tetrodotoxin (TTX), is a potent neurotoxin found in genetically diversed
      organisms. Many TTX producing microorganism have also been isolated from TTX
      bearing animals. The TTX producing microbes found in four different phylum
      (Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes), the
      Proteobacteria are the dominating one. In most of the cases, TTX producing
      microbes are found in the intestine of the TTX producing vector indicating the
      origin of TTX through food chain. This paper reviews the TTX and its analogs and
      the geographic distribution of TTX in symbiotic microorganism and its production.

PMID- 24121554
TI  - Elementary tetrahelical protein design for diverse oxidoreductase functions.
AB  - Emulating functions of natural enzymes in man-made constructs has proven
      challenging. Here we describe a man-made protein platform that reproduces many of
      the diverse functions of natural oxidoreductases without importing the complex
      and obscure interactions common to natural proteins. Our design is founded on an
      elementary, structurally stable 4-alpha-helix protein monomer with a minimalist
      interior malleable enough to accommodate various light- and redox-active
      cofactors and with an exterior tolerating extensive charge patterning for
      modulation of redox cofactor potentials and environmental interactions. Despite
      its modest size, the construct offers several independent domains for functional
      engineering that targets diverse natural activities, including dioxygen binding
      and superoxide and peroxide generation, interprotein electron transfer to natural
      cytochrome c and light-activated intraprotein energy transfer and charge
      separation approximating the core reactions of photosynthesis, cryptochrome and
      photolyase. The highly stable, readily expressible and biocompatible
      characteristics of these open-ended designs promise development of practical in
      vitro and in vivo applications. 

PMID- 24121557
TI  - Effect of bioactive substances found in rapeseed, raspberry and strawberry seed
      oils on blood lipid profile and selected parameters of oxidative status in rats.
AB  - Rapeseed, strawberry and raspberry seed oils are a rich source of polyunsaturated
      fatty acids and antioxidants such as tocols, bioflavonoids and phytosterols. The
      aim of the study was to determine changes in the blood lipid profile of rats fed
      with rapeseed, strawberry and raspberry seed oils and their effects on selected
      parameters of oxidative status. The experiment was carried out on male Wistar
      rats. The oils were administered by oral gavage for 5 weeks once daily at the
      dose of about 0.8 ml per rat. Blood samples were taken before and after
      supplementation period. The activity of superoxide dismutase (SOD) and
      glutathione peroxidase (cGPx) was assessed in erythrocytes and contents of
      triglycerides (TG), total cholesterol, low-density fraction of cholesterol (LDL)
      and high-density fraction of cholesterol (HDL) were assessed in plasma. The
      experiment shows that oils supplemented in the diet for 5 weeks had no
      significant effect on the level of triglyceride (TG), total cholesterol as well
      as HDL and LDL fractions. Reduced activity of cGPX and SOD in the group of rats
      receiving raspberry and strawberry seed oils suggests that these native oils may
      contribute to oxidative stability (improves antioxidant status). Thus, strawberry
      and raspberry seed oils can be considered as special biological oils, which
      constitute potential nutraceuticals reducing oxidative stress.

PMID- 24121558
TI  - Artificial intelligence in nanotechnology.
AB  - During the last decade there has been increasing use of artificial intelligence
      tools in nanotechnology research. In this paper we review some of these efforts
      in the context of interpreting scanning probe microscopy, the study of biological
      nanosystems, the classification of material properties at the nanoscale,
      theoretical approaches and simulations in nanoscience, and generally in the
      design of nanodevices. Current trends and future perspectives in the development
      of nanocomputing hardware that can boost artificial-intelligence-based
      applications are also discussed. Convergence between artificial intelligence and
      nanotechnology can shape the path for many technological developments in the
      field of information sciences that will rely on new computer architectures and
      data representations, hybrid technologies that use biological entities and
      nanotechnological devices, bioengineering, neuroscience and a large variety of
      related disciplines. 

PMID- 24121559
TI  - Isolation and th17 differentiation of naive CD4 T lymphocytes.
AB  - Th17 cells are a distinct subset of T cells that have been found to produce
      interleukin 17 (IL-17), and differ in function from the other T cell subsets
      including Th1, Th2, and regulatory T cells. Th17 cells have emerged as a central
      culprit in overzealous inflammatory immune responses associated with many
      autoimmune disorders. In this method we purify T lymphocytes from the spleen and
      lymph nodes of C57BL/6 mice, and stimulate purified CD4+ T cells under control
      and Th17-inducing environments. The Th17-inducing environment includes
      stimulation in the presence of anti-CD3 and anti-CD28 antibodies, IL-6, and TGF
      beta. After incubation for at least 72 hours and for up to five days at 37 
      degrees C, cells are subsequently analyzed for the capability to produce IL-17
      through flow cytometry, qPCR, and ELISAs. Th17 differentiated CD4+CD25- T cells
      can be utilized to further elucidate the role that Th17 cells play in the onset
      and progression of autoimmunity and host defense. Moreover, Th17 differentiation
      of CD4+CD25- lymphocytes from distinct murine knockout/disease models can
      contribute to our understanding of cell fate plasticity. 

PMID- 24121560
TI  - Smoking spaces as enabling spaces of wellbeing.
AB  - A persistent emphasis on the negative biomedical effects of cigarette smoking
      effectively glosses over the affectual-sensual and social wellbeing that smoking
      can enable. In addition, while tobacco research has recently been more attuned to
      the stigmatizing affects brought about by smoking de-normalization efforts, a lot
      less attention has been placed on how smokers negotiate these feelings of
      stigmatization so as to restore their personal spaces of wellbeing. In this
      paper, I situate my investigation of smoking geographies in the burgeoning
      literature on enabling spaces which focuses on how places co-constitute our
      ability to act/affect in empowering ways. By deploying qualitative research
      methods such as in-depth interviews, I argue that an acknowledgment of how
      smoking spaces in Singapore can be enabling along affectual, sensorial and social
      registers is long overdue. While it is not my purpose to systematically downplay
      the damaging health effects that smoking can engender, a focus on enabling
      smoking spaces emphasizes the role of smokers as creative agents capable of
      (re)fashioning their own holistic and subjective versions of wellbeing. In so
      doing, I hope to contribute to the existing research on smoking spaces and a
      recent profusion of work on relational geographies of affect. 

PMID- 24121561
TI  - Hydrolysis of the damaged deoxythymidine glycol nucleoside and comparison to
      canonical DNA.
AB  - Genomic integrity is continually under attack by both endogenous and exogenous
      sources. One of the most common forms of damage is oxidation of the thymine
      nucleobase to form (5R,6S)-dihydroxy-5,6-dihydro-thymine (thymine glycol or Tg),
      which stops DNA polymerases and is thus cytotoxic. Thymine glycol damage is
      repaired through a variety of mechanisms, including the multi-step base excision
      repair (BER) pathway. In the first BER step, the glycosidic bond of the dTg
      nucleotide is hydrolyzed by a DNA glycosylase. In order to understand the
      catalytic effect of the glycosylases, the corresponding uncatalyzed mechanisms
      and barriers are required, as well as an appreciation of the relative reactivity
      of the glycosidic bond with respect to the corresponding canonical nucleoside. To
      this end, the PCM-B3LYP/6-31+G(d) reaction potential energy surfaces (PES) for
      deoxythymidine (dT) and dTg hydrolysis are characterized in the present study
      using solvent-phase optimizations and a model containing three explicit water
      molecules. The surfaces are comparable to those generated using functionals that
      account for dispersion interactions (B3LYP-D3 and M06-2X). Mapping the PES as a
      function of the glycosidic bond length and nucleophile-sugar distance reveals a
      synchronous S(N)2 mechanism as the lowest energy pathway for damaged dTg
      hydrolysis, which contrasts the preferred dissociative S(N)1 mechanism isolated
      for the deglycosylation of natural dT. As proposed for other enzymes, the
      difference in excision pathway may at least in part help the enzyme selectively
      target the damaged base and discriminate against the natural counterpart.
      Interestingly, the barrier to dTg deglycosylation (DeltaG(?) = 138.0 kJ mol(-1))
      is much higher than for dT deglycosylation (DeltaG(?) = 112.7 kJ mol(-1)), which
      supports the stability of this lesion and clarifies the catalytic feat presented
      to DNA repair enzymes that remove this detrimental damage from the genome.
      Although nucleotide excision repair (NER) typically targets bulky DNA lesions,
      the large calculated barrier for dTg deglycosylation rationalizes why the NER
      mechanism also excises this non-bulky lesion from cellular DNA.

PMID- 24121562
TI  - Protector turns predator: Autophagic death via selective degradation of KRAS.
AB  - Therapy-induced autophagy is recognized as a critical determinant of treatment
      outcome in cancer patients, primarily as a factor underlying drug resistance.
      However, recent investigations point toward a context-dependent, death-inducing
      role for autophagy, the mechanism of which remains largely unknown. Our recent
      study provides evidence that autophagy can directly mediate cell killing in
      multiple tumor cell types by facilitating degradation of KRAS/K-Ras, a key
      survival protein. These findings have broad implications for strategies employing
      autophagy modulation to target tumor cells. 

PMID- 24121563
TI  - Increasing sensitivity of pulse EPR experiments using echo train detection
      schemes.
AB  - Modern pulse EPR experiments are routinely used to study the structural features
      of paramagnetic centers. They are usually performed at low temperatures, where
      relaxation times are long and polarization is high, to achieve a sufficient
      Signal/Noise Ratio (SNR). However, when working with samples whose amount and/or
      concentration are limited, sensitivity becomes an issue and therefore
      measurements may require a significant accumulation time, up to 12h or more. As
      the detection scheme of practically all pulse EPR sequences is based on the
      integration of a spin echo--either primary, stimulated or refocused--a
      considerable increase in SNR can be obtained by replacing the single echo
      detection scheme by a train of echoes. All these echoes, generated by Carr
      Purcell type sequences, are integrated and summed together to improve the SNR.
      This scheme is commonly used in NMR and here we demonstrate its applicability to
      a number of frequently used pulse EPR experiments: Echo-Detected EPR, Davies and
      Mims ENDOR (Electron-Nuclear Double Resonance), DEER (Electron-Electron Double
      Resonance|) and EDNMR (Electron-Electron Double Resonance (ELDOR)-Detected NMR),
      which were combined with a Carr-Purcell-Meiboom-Gill (CPMG) type detection scheme
      at W-band. By collecting the transient signal and integrating a number of
      refocused echoes, this detection scheme yielded a 1.6-5 folds SNR improvement,
      depending on the paramagnetic center and the pulse sequence applied. This
      improvement is achieved while keeping the experimental time constant and it does
      not introduce signal distortion.

PMID- 24121564
TI  - Nano-mineralogical investigation of coal and fly ashes from coal-based captive
      power plant (India): an introduction of occupational health hazards.
AB  - Coal derived nano-particles has been received much concern recently around the
      world for their adverse effects on human health and the environment during their
      utilization. In this investigation the mineral matter present in some
      industrially important Indian coals and their ash samples are addressed. Coal and
      fly ash samples from the coal-based captive power plant in Meghalaya (India) were
      collected for different characterization and nano-mineralogy studies. An
      integrated application of advanced characterization techniques such as X-ray
      diffraction (XRD), High Resolution-Transmission Electron microscopy (HR
      TEM)/(Energy Dispersive Spectroscopy) EDS/(selected-area diffraction pattern)
      SAED, Field Emission-Scanning Electron Microscopy (FE-SEM)/EDS analysis, and
      Mossbauer spectroscopy were used to know their extent of risks to the human
      health when present in coal and fly ash. The study has revealed that the coals
      contain mainly clay minerals, whilst glass fragments, spinel, quartz, and other
      minerals in lesser quantities were found to be present in the coal fly ash. Fly
      ash carbons were present as chars. Indian coal fly ash also found to contain
      nanominerals and ultrafine particles. The coal-fired power plants are observed to
      be the largest anthropogenic source of Hg emitted to the atmosphere and expected
      to increase its production in near future years. The Multi Walled Carbon Nano
      Tubes (MWCNTs) are detected in our fly ashes, which contains residual
      carbonaceous matter responsible for the Hg capture/encapsulation. This detailed
      investigation on the inter-relationship between the minerals present in the
      samples and their ash components will also be useful for fulfilling the clean
      coal technology principles. 

PMID- 24121565
TI  - Relating sediment impacts on coral reefs to watershed sources, processes and
      management: a review.
AB  - Modification of terrestrial sediment fluxes can result in increased sedimentation
      and turbidity in receiving waters, with detrimental impacts on coral reef
      ecosystems. Preventing anthropogenic sediment reaching coral reefs requires a
      better understanding of the specific characteristics, sources and processes
      generating the anthropogenic sediment, so that effective watershed management
      strategies can be implemented. Here, we review and synthesise research on
      measured runoff, sediment erosion and sediment delivery from watersheds to near
      shore marine areas, with a strong focus on the Burdekin watershed in the Great
      Barrier Reef region, Australia. We first investigate the characteristics of
      sediment that pose the greatest risk to coral reef ecosystems. Next we track this
      sediment back from the marine system into the watershed to determine the storage
      zones, source areas and processes responsible for sediment generation and run
      off. The review determined that only a small proportion of the sediment that has
      been eroded from the watershed makes it to the mid and outer reefs. The sediment
      transported >1 km offshore is generally the clay to fine silt (<4-16 MUm)
      fraction, yet there is considerable potential for other terrestrially derived
      sediment fractions (<63 MUm) to be stored in the near-shore zone and remobilised
      during wind and tide driven re-suspension. The specific source of the fine clay
      sediments is still under investigation; however, the Bowen, Upper Burdekin and
      Lower Burdekin sub-watersheds appear to be the dominant source of the clay and
      fine silt fractions. Sub-surface erosion is the dominant process responsible for
      the fine sediment exported from these watersheds in recent times, although
      further work on the particle size of this material is required. Maintaining
      average minimum ground cover >75% will likely be required to reduce runoff and
      prevent sub-soil erosion; however, it is not known whether ground cover
      management alone will reduce sediment supply to ecologically acceptable levels.

PMID- 24121566
TI  - Dynamics of microbial diversity profiles in waters of different qualities.
      Approximation to an ecological quality indicator.
AB  - Over the past two decades, the amount of reclaimed water has increased throughout
      the world to face the current water shortage, and as a consequence there is an
      increasing interest to develop good indicators of water quality, beyond the
      traditional fecal indicators. In order to meet this need, in this work the
      microbial profiles of different wastewater treatment plant effluents, both
      secondary and tertiary, were studied and compared with water samples from an
      uncontaminated natural aquifer. Taking into account the most abundant
      phylogenetic groups found in these water samples, we calculated the
      Bacteroidetes, Gammaproteobacteria and Nitrospira/Betaproteobacteria (BGN:beta)
      ratio and found significant differences between the mean ratios of the four water
      qualities. The secondary effluent ratios were never below 1.3 and the tertiary
      effluent and groundwater ratios were never over 0.85. Furthermore, calculation of
      this index with previous published data supports our results and indicates that
      the BGN:beta ratio is a possible alternative indicator of water quality. 

PMID- 24121567
TI  - Association of molecular markers derived from the BrCRTISO1 gene with prolycopene
      enriched orange-colored leaves in Brassica rapa [corrected]..
AB  - KEY MESSAGE: Sequence polymorphism in BrCRTISO1, encoding carotenoid isomerase,
      is identified in orange-colored B. rapa , and three resulting gene-based markers
      will be useful for marker-assisted breeding of OC cultivars. Carotenoids are
      color pigments that are important for protection against excess light in plants
      and essential sources of retinols and vitamin A for animals. We identified a
      single recessive gene that might cause orange-colored (OC) inner leaves in
      Brassica rapa. The inner leaves of the OC cultivar were enriched in lycopene-like
      compounds, specifically prolycopene and its isomers, which can be a useful
      functional trait for Kimchi cabbage. We used a candidate gene approach based on
      the 21 genes in the carotenoid pathway to identify a candidate gene responsible
      for the orange color. Among them, we focused on two carotenoid isomerase (CRTISO)
      genes, BrCRTISO1 and BrCRTISO2. The expression of BrCRTISO1 was higher than that
      of BrCRTISO2 in a normal yellow-colored (YE) cultivar, but full-length BrCRTISO1
      transcripts were not detected in the OC cultivar. Genomic sequence analysis
      revealed that BrCRTISO1 of the OC cultivar had many sequence variations,
      including single nucleotide polymorphisms (SNPs) and insertions and deletions
      (InDels), compared to that of the YE cultivar. We developed molecular makers for
      the identification of OC phenotype based on the polymorphic regions within
      BrCRTISO1 in B. rapa breeding. The BrCRTISO1 gene and its markers identified in
      this study are novel genetic resources and will be useful for studying the
      carotenoid biosynthesis pathway as well as developing new cultivars with unique
      carotenoid contents in Brassica species.

PMID- 24121568
TI  - Resistance to stem rust Ug99 in six bread wheat cultivars maps to chromosome 6DS.
AB  - KEY MESSAGE: Identified SSR markers ( Xcfd49 and Xbarc183 ) linked with stem rust
      resistance for efficient use in marker-assisted selection and stacking of
      resistance genes in wheat breeding programs. More than 80 % of the worldwide
      wheat (Triticum aestivum L.) area is currently sown with varieties susceptible to
      the Ug99 race group of stem rust fungus. However, wheat lines Niini, Tinkio,
      Coni, Pfunye, Blouk, and Ripper have demonstrated Ug99 resistance at the seedling
      and adult plant stages. We mapped stem rust resistance in populations derived
      from crosses of a susceptible parent with each of the resistant lines. The
      segregation of resistance in each population indicated the presence of a single
      gene. The resistance gene in Niini mapped to short arm of chromosome 6D and was
      flanked by SSR markers Xcfd49 at distances of 3.9 cM proximal and Xbarc183 8.4 cM
      distal, respectively. The chromosome location of this resistance was validated in
      three other populations: PBW343/Coni, PBW343/Tinkio, and Cacuke/Pfunye.
      Resistance initially postulated to be conferred by the SrTmp gene in Blouk and
      Ripper was also linked to Xcfd49 and Xbarc183 on 6DS, but it was mapped proximal
      to Xbarc183 at a similar position to previously mapped genes Sr42 and SrCad.
      Based on the variation in diagnostic marker alleles, it is possible that Niini
      and Pfunye may carry different resistance genes/alleles. Further studies are
      needed to determine the allelic relationships between various genes located on
      chromosome arm 6DS. Our results provide valuable molecular marker and genetic
      information for developing Ug99 resistant wheat varieties in diverse germplasm
      and using these markers to tag the resistance genes in wheat breeding.

PMID- 24121569
TI  - [Publishing articles in English in Spanish speaking medical journals: does it
      really not increase its citation by indexed journals?].

PMID- 24121570
TI  - [Visual outcome in patients with macroprolactinoma treated with dopamine
      agonists].
AB  - BACKGROUND: Dopamine agonists (DA) effectively reduce tumor size of
      macroprolactinomas, with the consequent improvement of eventual visual
      impairment. AIM: To study the visual outcomes in patients with macroprolactinoma
      treated with DA. MATERIAL AND METHODS: Retrospective cohort study which included
      patients with macroprolactinoma controlled at a Neuro-endocrinology and Neuro
      ophthalmology Department between 1997 and 2011, and treated exclusively with DA
      (bromocriptine or cabergoline). Patients who were operated or had previous
      radiotherapy and those with an incomplete follow up, were excluded. We analyzed
      and compared the visual status before and after the beginning of DA treatment.
      RESULTS: Thirty one patients aged 8 to 59 years, were included. Eighteen patients
      (58%) had visual impairment at the moment of diagnosis (group 1) and 13 had no
      alterations (group 2). Mean follow up was 36.5 months. Fifteen patients from
      group 1 (83%) had visual improvement, two remained stable (11 %) and one had a
      visual deterioration (6%). In group 2, only one non-compliant patient had a
      visual deterioration. CONCLUSIONS: DAs are effective in the management of neuro
      ophthalmic complications associated to macroprolactinomas and should be
      considered as first choice therapy in these tumors.

PMID- 24121571
TI  - [Association of carotid intima-media thickness with traditional cardiovascular
      risk and metabolic factors].
AB  - BACKGROUND: Carotid intima-media thickness (IMT) is a surrogate marker of
      subclinical atherosclerosis and is associated with cardiovascular risk factors
      (CVRF) AIM: To analyze the association of CVRF and metabolic factors (MF) with
      IMT, and if the clustering of these factors modify IMT. MATERIAL AND METHODS:
      Cross sectional study in 187 participants aged 46+/-10 years (53% male) without
      CV disease. Weight, height, waist circumference (WC), blood pressure, fasting
      plasma glucose and lipid profile were measured. Abdominal obesity (AOb) was
      defined by ATP III criteria. Mean carotid IMT was measured at the far wall of the
      common carotid artery. The cutoff point for an abnormally high IMT was set at the
      75th IMT percentile of the sample. RESULTS: The 75th IMT percentile of the sample
      was 0.67 mm. In a multivariate analysis four factors were significantly related
      with a high IMT: age (odds ratio (OR): 5.3, confidence intervals (CI): 2.2-12.9),
      dyslipidemia (OR: 6.4 CI: 2.3-17.9), systolic blood pressure (OR: 2.9, CI: 1.2
      7.1) and AOb (OR: 2.9 (IC: 1.1-7.2). The presence of Oto 4 of these factors was
      associated with an IMT increment from 0.54 to 0.71 mm (p < 0,001). CONCLUSIONS:
      In this sample dyslipidemia, systolic blood pressure and abdominal obesity were
      the main predictors of a high IMT.

PMID- 24121572
TI  - [Survey on moral judgment criteria among medical students].
AB  - BACKGROUND: The evaluation of moral judgment criteria in medical students is
      important to develop effective educational programs in bioethics. AIM: To compare
      priority judgment criteria and moral judgment tendency in medical students of
      first and fifth grade. MATERIAL AND METHODS: The Moral Foundations Questionnaire
      (MFQ30), to identify moral criteria was applied to 259 students, 63.7% from first
      year and 50.2% women. RESULTS: The dominant moral tendency both in first and
      fifth year students was liberal. Justice and compassion were the most important
      criteria in men and in women, respectively. Respect towards authority and
      sanctity were the least important criteria in women and men, respectively.
      CONCLUSIONS: The implications for moral psychology and medical education of these
      results are discussed.

PMID- 24121573
TI  - [Effects on academic performance of a leveling program in basic sciences in first
      year medical students].
AB  - BACKGROUND: A significant number of students in health careers do not have the
      knowledge to approve basic courses. Therefore, educational programs to level off
      knowledge have been developed. AIM: To associate the results of a leveling
      program with the academic performance in cell biology (CB) and biochemistry (BC)
      of first year medical students. MATERIAL AND METHODS: We applied a test to first
      year medical students at the beginning and end of the leveling program (control
      test). The results obtained at the end of the leveling program were correlated
      with the results obtained in CB and BC. RESULTS: Fifty seven of 89 (64%) first
      year medical students met the study entry criteria (54% female). Students who
      completed the leveling program had a significantly higher approval rate in CB
      (93% versus 75%, P = 0.024), and in BC (95% versus 69%, P = 0.001). After
      completing the leveling program, the risk of failing CB and BC, decreased by 72
      and 84% respectively. CONCLUSIONS: This study shows that medical students who
      participate in the leveling program decrease the chances of failing in CB and BC.

PMID- 24121574
TI  - [Latin American medical students' appraisal on university scientific research
      training].
AB  - BACKGROUND: Learning research skills should be a goal during undergraduate
      training of physicians. AIM: To identify Latin American medical students'
      appraisal on research skills university training. MATERIAL AND METHODS: A self
      administered survey about experience in research, self-assessment of research
      skills, quality of training in the area received at the university and that
      importance of publishing as undergraduate students, was answered by 208 medical
      students aged 23 +/- 3 years (54% male), attending a medical students congress.
      RESULTS: Seventy percent of respondents pertained to medical students' scientific
      societies and 34% had published in a scientific journal. Fifty two percent
      considered as good or very good the training level received at their universities
      on information retrieval and 45% considered good the training in research
      methodology. Thirty two percent considered as poor or none the training received
      in scientific writing and 37% in the publishing process. Eighty nine percent
      considered student publishing as important and 61% perceived limitations in this
      matter. CONCLUSIONS: The university training level received by Latin American
      medical students on research and publication process was evaluated as deficient
      by these students.

PMID- 24121575
TI  - [Validation of BR23 questionnaire for the assessment of quality of life of breast
      cancer patients in Chile].
AB  - BACKGROUND: Quality of Life assessment in oncologic patients evaluates the impact
      and sequels of the disease ana the adverse effects of available treatments. AIM:
      To validate in Chile the breast cancer specific-questionnaire (BR23) developed by
      the European Organization for Research and Treatment of Cancer (EORTC). PATIENTS
      AND METHODS: After performing a linguistic validation of the BR23 according to
      EORTC instructions, its psychometric properties were tested in 103 patients with
      breast cancer whose ages ranged from 34 to 83 years. Internal consistency of the
      scales was assessed using the Cronbach's alpha coefficient. The test-retest
      correlations of each scale (n = 83) were evaluated. The correlation of BR23
      scales with SF36 version 2 and C30 version 3.0 scales was also assessed. The
      sensitivity and specificity of the instrument were analyzed using receiver
      operating characteristic curves (ROC). RESULTS: Alpha values showed acceptable
      levels of internal consistency, ranging between 0.702 and 0.917 in all scales of
      BR23. The statistical analysis revealed significant test-retest correlations in
      most scales of BR23. The correlations between BR23 and similar domains of C30 and
      SF36 questionnaires were also significant. The BR23 questionnaire demonstrated
      satisfactory levels of sensitivity and specificity when compared with the SF-36
      scale. CONCLUSIONS: The BR23 questionnaire adapted for use in Chile is
      linguistically appropriate and psychometrically valid.

PMID- 24121576
TI  - [Impact of a psychomotor re-education guide on the quality of life of patients
      with Alzheimer's disease].
AB  - BACKGROUND: We developed a psychomotor re-education guide (PSEG) adapted to
      people with Alzheimer disease (AD), including a cognitive stimulation program
      integrated with the exercise recommendations of the American College of Sports
      Medicine. AIM: To evaluate the effect of the PSEG on cognitive and functional
      parameters among patients with AD. PATIENTS AND METHODS: We applied the PSEG to
      64 participants with AD aged 64 to 87 years (55% women) during 12 months. At
      baseline and the end of the intervention, cognitive abilities (Mini Mental
      State), fitness (Chair Stand test), level of independence (Barthel Index) and
      quality of life (QoL) (SF-12) were assessed. RESULTS: The application of PSEG
      resulted in a significant improvement in the QoL and physical capacity of
      patients with AD. Cognitive ability declined along with disease progression.
      CONCLUSIONS: These results demonstrate the effectiveness of the guide in mild and
      moderate stages of AD improving the physical fitness and the QoL.

PMID- 24121577
TI  - [Association of exhaled nitric oxide with asthma and atopy among children living
      in Santiago, Chile].
AB  - BACKGROUND: Chronic airway inflammation is a central process in asthma.
      Measurement of exhaled nitric oxide (eNO) is a non-invasive biomarker of
      eosinophilic airway inflammation. AIM: To measure eNO levels in a population of
      asthmatic and non-asthmatic children and to evaluate their relationship with
      asthma and atopy. MATERIAL AND METHODS: We studied 143 asthmatic and non
      asthmatic children aged 6 to 14 years attended a hospital and primary health
      service. Participants were tested for allergies and followed during the winter
      months of 2010 and 2011. They were visited regularly at their homes and eNO
      levels were measured on each visit using a handheld equipment. Mean eNO
      distribution were compared by the presence of asthma or atopy using t-test and
      regression models. RESULTS: No significant differences for mean eNO levels were
      detected, according to presence of asthma or atopy, by any of the statistical
      methods used. Regression models showed significant effects for age but not for
      sex. CONCLUSIONS: There were no differences in eNO levels in the studied children
      by the presence of asthma or atopy.

PMID- 24121578
TI  - [Effects of wheat flour fortification with folic acid on the prevalence of neural
      tube defects in Chile].
AB  - BACKGROUND: Congenital malformations (CMF) have an important role in infant
      mortality. Neural tube defects (NTD) have great relevance from both social and
      public health points of view. The ECLAMC (Collaborative Latin American Study of
      Congenital Malformations) maintains in Chile an epidemiological surveillance of
      CMF prevalence rate at birth since 1969. AIM: To assess the effect of wheat flour
      folic acid fortification on the prevalence of NTD. PATIENTS AND METHODS: Only
      Anencephaly, Spina bifida and Cephalocele were considered as NTD. All children
      born in the maternities incorporated to ECLAMC between 1969 and 1999 were
      considered as belonging to the pre folic acid fortification period and those who
      were born from 2001 to 2010 were considered as belonging to the post
      fortification period. RESULTS: The NTD prevalence rate at birth in the pre
      fortification period was 17.03/10,000. In the second period, there were 291,996
      births and among them, 280 newborns were affected by a form of NTD (9.59 in
      10,000 births). This represents a 44% decrease (p < 0.01). Anencephaly rate fell
      from 7.16/10,000 to 3.67/10,000, representing a 49% lower rate (p < 0.01). Spina
      bifida rate decreased from 8.61/10,000 to 4.49/10,000, representing a 48% lower
      rate (p < 0.01). Cephalocele had a 20% non-significant reduction. CONCLUSIONS:
      Wheat flour fortification with folic acid reduced by 44% the prevalence rate of
      NTD at birth. This means that NTDs were prevented in 185 Chilean newborns each
      year.

PMID- 24121579
TI  - [Freezing and gait disorders in Parkinson's disease].
AB  - More than one third of patients with Parkinson disease experience freezing. It is
      characterized by the feeling that one's feet are "glued to the floor", and it is
      more common in the later stages of the disease. The causes of this gait disorder
      are not yet fully established, but it may lead patients to suffer falls and lose
      their independence. As a consequence, the development of therapeutic measures
      which can overcome freezing is of fundamental important for the autonomy of such
      individuals. There is no consensus in the literature on the most recommended
      therapeutic measures for the prevention or attenuation of freezing in gait. What
      seems to be defined are the phenomenological aspects of the disorder and good
      therapy, represented by the association between drug therapy and sensorial
      stimuli or motor coordination training geared towards the specificities to avoid
      motor difficulties of freezing, when triggering factors are present. 

PMID- 24121580
TI  - [Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: advances in
      pathogenesis and treatment].
AB  - ANCA (anti-neutrophil cytoplasmic antibodies) associated vasculitis or AAV are a
      group of diseases with predominant inflammation of small vessels and the presence
      of detectable ANCA in serum. Due to these common features, it is considered that
      AAV share pathogenic mechanisms. Consequently, a similar therapeutic approach has
      been developed. A new nomenclature has been recently proposed, with AAV including
      "granulomatosis with polyangiitis" (GPA, formerly Wegener's granulomatosis),
      "microscopic polyangiitis" (MPA), "eosinophilic granulomatosis with polyangiitis"
      (EGPA, formerly Churg-Strauss disease) and renal limited vasculitis. Research on
      AAV has shown significant advances in the last two decades, including advances in
      the knowledge of pathogenic mechanisms such as the pro-inflammatory role of ANCA,
      AAV murine models and genetic links. Evidence on previous immunosuppressive
      therapies has improved significantly and new, promissory drugs have been
      introduced, Rituximab being the most important. We review the advances of
      pathogenic mechanisms and treatment for these diseases.

PMID- 24121581
TI  - [Edvard Munch: disease and genius of the great Norwegian artist].
AB  - Edvard Munch is one the most transcendental artists of all times. His work is
      innovative in terms of reflecting the grief, sadness, loneliness and the impact
      of death in human beings as no one did it before. Behind his work it is possible
      to find many clues given by Munch himself of the reason of his creativity: a
      childhood surrounded by death and sorrow, and the development of an affective
      disorder that led him to alcoholism and many hospitalizations due to psychotic
      episodes. In this review, we analyze Munch's life and his disease that
      undoubtedly contributed to his great artistic legacy. 

PMID- 24121582
TI  - [Organizing health care: an ethical perspective].
AB  - Health care at population level is a complex problem. Having this in mind, the
      purpose of this paper is to focus on the goods that are ethically relevant in the
      process of caring for health at this level. We briefly analyze some of the
      Chilean health statistics that, although they show important improvements along
      the years, demonstrate that certain conditions are to be deemed as inadequate by
      both healthcare providers and patients. Ethics is a central component to
      determine how to structure and organize health care systems and how they should
      operate. We emphasize human dignity as an ethical corner stone of the health care
      system, along with other important values such as justice and humanization, under
      the scope of the ends of medicine, and other components such as technical
      competence of providers and the financing of the whole process. We conclude that
      as far as a health care system is organized in a way that medical practice is
      well ordered, primarily and fundamentally according the ends of medicine and the
      good of persons, such a health care system is ethically adequate.

PMID- 24121583
TI  - [Perceptions about continuous training of Chilean health care teachers].
AB  - BACKGROUND: Continuous training of teachers, in discipline and pedagogical
      topics, is a key step to improve the quality of educational processes. AIM: To
      report the perception of Chilean teachers of undergraduate health care programs,
      about continuous training activities. MATERIAL AND METHODS: Twenty teachers
      working at different undergraduate health care programs in Chile were
      interviewed. Maximum variation and theoretical sampling methods were used to
      select the sample. Data was analyzed by open coding, according to the Grounded
      Theory guidelines. RESULTS: Nine categories emerged from data analysis: Access to
      continuous training, meaning of training in discipline, activities of continuous
      training in discipline, meaning of continuous training in pedagogy, kinds of
      continuous training in pedagogy, quality of continuous training in pedagogy,
      ideal of continuous training in pedagogy, outcomes of continuous training in
      pedagogy and needs for continuous training in pedagogy. CONCLUSIONS: Teachers of
      health care programs prefer to participate in contextualized training activities.
      Also, they emphasize their need of training in evaluation and teaching
      strategies.

PMID- 24121584
TI  - Asymptomatic bilateral elongated and mineralized stylohyoid complex: report of
      one case.
AB  - The stylohyoid process is a cylindrical bony structure surrounded by important
      anatomical structures including vessels and nerves. Calcification and elongation
      of the stylohyoid ligament complex over 30 mm may be associated with neck and
      facial pain, known as Eagle's syndrome. However, a bilateral ossified and
      elongated stylohyoid complex may be devoid of symptoms. We report a 79-year-old
      symptom-free female who presented on a routine conventional dental radiographic
      exam an 80.96 mm pseudoarticulated stylohyoid complex in the left side and an
      75.85 mm on the other. On CAT scan, both processes were calcified.

PMID- 24121585
TI  - [Hemolytic-uremic syndrome associated with gemcitabine use: report of one case].
AB  - Gemcitabine is a widely used drug in the treatment of advanced pancreatic cancer
      and other malignancies. It is generally well tolerated and exceptionally its use
      has been associated with hemolytic-uremic syndrome, causing acute kidney injury,
      hypertension, chronic renal failure requiring dialysis, and death. We report a 60
      year-old man with pancreatic carcinoma and regional lymph node invasion, whom
      after four months of therapy with gemcitabine and after dose number 11, suddenly
      developed an acute nephritic syndrome with moderate renal impairment, associated
      with severe anemia (hemoglobin 6.0 g/dL) and thrombocytopenia (20,000 mm3). Renal
      biopsy showed the classic findings of thrombotic microangiopathy Gemcitabine was
      discontinued and renal function and hematological parameters gradually improved.

PMID- 24121586
TI  - Diffuse idiopathic skeletal hyperostosis causing dysphagia in a young patient.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is an under-diagnosed condition
      producing flowing ossification of the antero-lateral ligaments of the spine.
      Affecting predominantly males over 65 years old, it is an unusual cause of
      dysphagia and dysphonia. We report a 45-year-old mole with a three years history
      of dysphonia and three months of dysphagia. The initial diagnosis was
      gastroesophageal reflux, and an endoscopy ruled out esophageal luminal pathology.
      Cervical spine radiographs showed ossification of the cervical anterior
      longitudinal ligament with large, prominent osteophytes from C3 to C6, producing
      esophageal and upper airway compression; these images were compatible with DISH.
      Cervical osteophyte resection resulted in complete resolution of symptoms. DISH
      should be considered in the differential diagnosis of dysphagia and dysphonia. 

PMID- 24121587
TI  - [Publishing articles in English in Spanish speaking medical journals: does it
      really not increase its citation by indexed journals?].

PMID- 24121589
TI  - [Is the tiger spider, Scytodes globula, an effective predator of the brown
      recluse spider, Loxosceles laeta?].

PMID- 24121588
TI  - [Probiotics as an alternative to prevent recurrent urinary tract infections in
      women].

PMID- 24121590
TI  - [The use of e-mail in the communication between physicians and their patients].

PMID- 24121591
TI  - Food waste and food processing waste for biohydrogen production: a review.
AB  - Food waste and food processing wastes which are abundant in nature and rich in
      carbon content can be attractive renewable substrates for sustainable biohydrogen
      production due to wide economic prospects in industries. Many studies utilizing
      common food wastes such as dining hall or restaurant waste and wastes generated
      from food processing industries have shown good percentages of hydrogen in gas
      composition, production yield and rate. The carbon composition in food waste also
      plays a crucial role in determining high biohydrogen yield. Physicochemical
      factors such as pre-treatment to seed culture, pH, temperature
      (mesophilic/thermophilic) and etc. are also important to ensure the dominance of
      hydrogen-producing bacteria in dark fermentation. This review demonstrates the
      potential of food waste and food processing waste for biohydrogen production and
      provides a brief overview of several physicochemical factors that affect
      biohydrogen production in dark fermentation. The economic viability of
      biohydrogen production from food waste is also discussed. 

PMID- 24121592
TI  - Implementing a comprehensive approach for evaluating significance and disturbance
      in protected karst areas to guide management strategies.
AB  - Many environmental studies have acquired an almost exclusively biotic perspective
      over the years, neglecting important key land characteristics like those of a
      geological and hydrological nature. This situation leads to incomplete, and even
      inappropriate, management strategies, particularly unjustified in the case of
      karst environments which form the basis of important protected areas around the
      world and are inherently very fragile environments compared to other natural
      systems. This study presents a holistic methodological approach to analyse the
      level of significance and disturbance in the Natural Park of Aralar (Basque
      Country, northern Spain) using two standardized indices: zonal Karst Significance
      Index (KSIZ) and zonal Karst Disturbance Index (KDIZ). The distribution of both
      indices in the park is based on the Geographic Information System (GIS). Thus,
      thematic maps regarding geological, geomorphological, biological, hydrological
      and cultural aspects provide the essential data for this work. The obtained
      results enable us to recognize the most significant and disturbed sectors of the
      park. These indices are subsequently combined to generate the Priority Management
      Index (PMI), which determine the different management needs of the territory.
      This comprehensive information not only serves efforts to better manage protected
      karst areas, but also to provide a snapshot view of the researched area to
      compare achieved results over time. 

PMID- 24121594
TI  - Facile synthesis and application of a carbon foam with large mesopores.
AB  - By combining elements of hard- and soft-templating, a facile synthesis method for
      carbon foams with large mesopores has been demonstrated. A commercial Pluronic
      surfactant was used as the structure-directing agent as well as the carbon
      precursor. No micelle swelling agent or post treatment is necessary to enlarge
      mesopores. As such this method requires fewer synthesis steps and is highly
      scalable. The as-synthesized meso-carbons showed potential applications in the
      fields of carbon oxide capture and lithium-sulfur batteries. 

PMID- 24121593
TI  - Clinical significance of the interaction between non-coding RNAs and the
      epigenetics machinery: challenges and opportunities in oncology.
AB  - Non-coding RNAs and epigenetics are remarkable mechanisms of cellular control. In
      this review we underline the processes by which non-coding RNAs (ncRNAs), shown
      to be involved in various diseases, are capable of modifying and being modified
      by the epigenetic machinery, emphasizing the clinical importance of this network
      in cancer. Many ncRNAs have been described that play important roles in the
      establishment and maintenance of the epigenome. However, only a few studies
      deeply take into account the role of ncRNAs from a clinicopathological
      standpoint. The wide range of interactions between the non-coding RNome and the
      epigenome, and the roles of these networks in the pathogenesis, prognosis and
      early diagnosis of many diseases, present new challenges and opportunities for
      future studies regarding therapeutic strategies in oncology. 

PMID- 24121595
TI  - One-step synthesis of Mn3O4/reduced graphene oxide nanocomposites for oxygen
      reduction in nonaqueous Li-O2 batteries.
AB  - A Li-O2 battery based on the Mn3O4/RGO nanocomposite (monodispersed Mn3O4
      nanoparticles supported on RGO) cathode exhibits excellent ORR activity and an
      outstanding initial discharge capacity as high as 16,000 mA h g(-1).

PMID- 24121597
TI  - Significant scales in community structure.
AB  - Many complex networks show signs of modular structure, uncovered by community
      detection. Although many methods succeed in revealing various partitions, it
      remains difficult to detect at what scale some partition is significant. This
      problem shows foremost in multi-resolution methods. We here introduce an
      efficient method for scanning for resolutions in one such method. Additionally,
      we introduce the notion of "significance" of a partition, based on subgraph
      probabilities. Significance is independent of the exact method used, so could
      also be applied in other methods, and can be interpreted as the gain in encoding
      a graph by making use of a partition. Using significance, we can determine "good"
      resolution parameters, which we demonstrate on benchmark networks. Moreover,
      optimizing significance itself also shows excellent performance. We demonstrate
      our method on voting data from the European Parliament. Our analysis suggests the
      European Parliament has become increasingly ideologically divided and that
      nationality plays no role.

PMID- 24121598
TI  - Non-hormonal methods for induction of labour.
AB  - PURPOSE OF REVIEW: The percentage of induced live birth has more than doubled
      from the 1990s to 2008. Induction of labour can either be based on medical
      indications, or performed as an elective procedure. A large range of
      pharmacological and non-pharmacological modalities are available for the
      induction of labour and the optimal method for labour induction is unknown. This
      article is aimed to examine literature on non-hormonal methods for labour
      induction, published from January 2012 to May 2013. RECENT FINDINGS: Eleven
      studies were identified in our search and included into the review. Foley balloon
      catheter appears to be more cost-effective and commonly used non-hormonal
      technique for induction of labour, although further meta-analysis is required in
      this area. Currently, there is not enough evidence to support routine use in all
      women for labour induction among other methods including amniotomy, acupuncture,
      sexual intercourse, isosorbide mononitrate, hypnosis, castor oil and breast
      stimulation. The latest three studies suggest that amniotomy may increase need
      for oxytocin augmentation during labour induction. SUMMARY: Many non-hormonal
      methods for labour induction still require further evidence to support their use
      within the clinical setting. Balloon catheter seems to be a more widely accepted
      non-hormonal method that has been supported by various literatures.

PMID- 24121599
TI  - How do we define the term idiopathic?
AB  - PURPOSE OF REVIEW: The term idiopathic is often used to describe a disease with
      no identifiable cause. It may be a diagnosis of exclusion; however, what specific
      minimum investigations need to be performed to define idiopathic is not always
      clear. This commentary describes the problems inherent in reaching a definition
      for the term idiopathic. RECENT FINDINGS: There is limited literature describing
      methodology to define a condition with no clear diagnostic criteria. This article
      offers chronic pelvic pain (CPP) syndrome as an example, in which structured
      qualitative interviews, literature searches and group consensus discussions were
      undertaken to produce a working definition for idiopathic CPP. SUMMARY: It is
      important to correctly develop these standardized definitions for use as outcome
      measures in research and as clinical indicators in healthcare.

PMID- 24121596
TI  - Autophagy: regulation and role in development.
AB  - Autophagy is an evolutionarily conserved cellular process through which long
      lived proteins and damaged organelles are recycled to maintain energy
      homeostasis. These proteins and organelles are sequestered into a double-membrane
      structure, or autophagosome, which subsequently fuses with a lysosome in order to
      degrade the cargo. Although originally classified as a type of programmed cell
      death, autophagy is more widely viewed as a basic cell survival mechanism to
      combat environmental stressors. Autophagy genes were initially identified in
      yeast and were found to be necessary to circumvent nutrient stress and
      starvation. Subsequent elucidation of mammalian gene counterparts has highlighted
      the importance of this process to normal development. This review provides an
      overview of autophagy, the types of autophagy, its regulation and its known
      impact on development gleaned primarily from murine models. 

PMID- 24121600
TI  - Over-the-counter access to oral contraceptives as a reproductive healthcare
      strategy.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize the current evidence on
      the safety and effectiveness of moving oral contraceptives from prescription-only
      to over-the-counter (OTC) status. The review also examines women's interest in
      OTC access to oral contraceptives, as well as potential barriers and facilitators
      to an OTC switch. RECENT FINDINGS: Studies show that women can safely self-screen
      for contraindications to oral contraceptives - especially progestin-only pills -
      without the aid of a clinician. One study in Texas found that women using pills
      obtained OTC in Mexico were significantly less likely to discontinue compared to
      women obtaining pills at US clinics by prescription. A national representative
      survey of US women at risk of unintended pregnancy found widespread interest in
      using OTC pills, and many women worldwide already have access to pills without a
      prescription. On average, the most US women report being willing to pay for an
      OTC pill is $20. SUMMARY: OTC access to oral contraceptives could help to reduce
      unintended pregnancy by increasing the number of pill users, improve continuation
      and reduce gaps in use. It is critical that a future OTC pill be made available
      at an accessible price, and it should be covered by insurance without a
      prescription. Research suggests that common concerns about the safety of oral
      contraceptives OTC and a potential negative effect on women's use of preventive
      services are largely unsupported.

PMID- 24121601
TI  - Study of optical phase conjugation in amorphous Zn(x)-S(y)-Se(100-x-y)
      chalcogenide thin films using degenerate four-wave mixing.
AB  - Degenerate four-wave mixing (DFWM) experiment is performed to obtain light
      wavefront inversion (phase conjugation) in semiconducting chalcogenide thin
      films. Third order nonlinearity of amorphous Zn(x)-S(y)-Se(100-x-y) chalcogenide
      thin films using DFWM technique is studied at second harmonic of Nd:YAG laser.
      Influence of total input irradiance on phase conjugate signal is deliberated
      using log-log plot that has a slope of three and hence implies third order
      nonlinearity. The dependence of phase conjugate signal on forward beam and
      backward beam is also studied. The period of the grating formed by interference
      of forward and probe beam is determined. As the temporal overlapping and sample
      thickness conditions are satisfied, the third order nonlinear susceptibility,
      figure of merit and nonlinear refractive index of amorphous films are estimated.
      The nonlinear behavior is analyzed in terms of decrease in band gap with
      increasing Zinc and decreasing Sulfur content.

PMID- 24121602
TI  - Structural characterization and vibrational spectroscopy of the arsenate mineral
      wendwilsonite.
AB  - In this paper, we have investigated on the natural wendwilsonite mineral with the
      formulae Ca2(Mg,Co)(AsO4)2?2(H2O). Raman spectroscopy complimented with infrared
      spectroscopy has been used to determine the molecular structure of the
      wendwilsonite arsenate mineral. A comparison is made with the roselite mineral
      group with formula Ca2B(AsO4)2?2H2O (where B may be Co, Fe(2+), Mg, Mn, Ni, Zn).
      The Raman spectra of the arsenate related to tetrahedral arsenate clusters with
      stretching region shows strong differences between that of wendwilsonite and the
      roselite arsenate minerals which is attributed to the cation substitution for
      calcium in the structure. The Raman arsenate (AsO4)(3-) stretching region shows
      strong differences between that of wendwilsonite and the roselite arsenate
      minerals which is attributed to the cation substitution for calcium in the
      structure. In the infrared spectra complexity exists of multiple to tetrahedral
      (AsO4)(3-) clusters with antisymmetric stretching vibrations observed indicating
      a reduction of the tetrahedral symmetry. This loss of degeneracy is also
      reflected in the bending modes. Strong Raman bands around 450 cm(-1) are assigned
      to nu4 bending modes. Multiple bands in the 350-300 cm(-1) region assigned to nu2
      bending modes provide evidence of symmetry reduction of the arsenate anion. Three
      broad bands for wendwilsonite found at 3332, 3119 and 3001 cm(-1) are assigned to
      OH stretching bands. By using a Libowitzky empirical equation, hydrogen bond
      distances of 2.65 and 2.75A are estimated. Vibrational spectra enable the
      molecular structure of the wendwilsonite mineral to be determined and whilst
      similarities exist in the spectral patterns with the roselite mineral group,
      sufficient differences exist to be able to determine the identification of the
      minerals.

PMID- 24121603
TI  - Optical and structural investigation of Dy3+-Nd3+ co-doped in magnesium lead
      borosilicate glasses.
AB  - MgO-PbO-B2O3-SiO2-Nd2O3-Dy2O3 glasses are prepared by melt-quenching technique.
      The samples are characterized by X-ray diffraction (XRD), optical absorption,
      luminescence and Fourier transform infrared (FT-IR) spectral studied. XRD
      analysis evidently indicates that the prepared samples are fully amorphous
      nature. From the optical absorption spectra, the bonding environment surrounding
      the Dy(3+) and their energy level scheme in glass network is analyzed.
      Enhancement of Dy(3+) emission by non-radiative energy transfers from Nd(3+) has
      been observed here. The samples emits intensive bluish yellow color from the
      (4)F9/2->(6)H15/2, (6)H13/2 transition of Dy(3+) ions in these glasses which are
      nearer to white light and it is also supported by the chromaticity color
      coordinates. The FT-IR spectra reveal that network connectivity is increased with
      replacement of bonds B-O-B, Si-O-Si by more resistant B-O-Si bonds with gradually
      increasing the content of Dy(3+) ions in the glass network. Along with
      spectroscopic parameters some physical parameters like density, refractive index
      etc. are measured for the glasses. 

PMID- 24121604
TI  - Asymmetric 1,8/13,2,x-M2C2B10 14-vertex metallacarboranes by direct electrophilic
      insertion reactions; the VCD and BHD methods in critical analysis of cage C atom
      positions.
AB  - The isolation of six isomeric, low-symmetry, dicobaltacarboranes with bicapped
      hexagonal antiprismatic cage structures, always in low yield, is described from
      reactions in which 13-vertex cobaltacarborane anions and sources of cobalt
      containing cations were present. The vertex-to-centroid distance (VCD) and boron
      H distance (BHD) methods are used to locate the correct C atom positions in the
      cages, thus allowing the compounds to be identified as 1,13-Cp2-1,13,2,10-closo
      Co2C2B10H12 (1), 1,8-Cp2-3-OEt-1,8,2,10-closo-Co2C2B10H11 (2), 1,13-Cp2-1,13,2,9
      closo-Co2C2B10H12 (3), 1,8-Cp2-1,8,2,4-closo-Co2C2B10H12 (4), 1,13-Cp2-1,13,2,4
      closo-Co2C2B10H12 (5) and 1,8-Cp2-1,8,2,5-closo-Co2C2B10H12 (6). It is shown that
      a common alternative method of cage C atom identification, using refined (as B)
      U(eq) values, does not work well, at least in these cases. Having identified the
      correct isomeric forms of the six dicobaltacarboranes, their syntheses are
      tentatively rationalised in terms of the direct electrophilic insertion of a
      {CpCo(+)} fragment into [CpCoC2B10](-) anions and it is demonstrated that
      compounds 1, 4, 5 and 6 can be successfully prepared by deliberately performing
      such reactions.

PMID- 24121605
TI  - A self-paired comparison of perioperative outcomes before and after
      implementation of a clinical pathway in patients undergoing total knee
      arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: Clinical pathways commonly modify multiple variables
      and deviate from long-established clinical practices. Therefore, it is difficult
      to perform prospective, randomized clinical trials comparing "standard care" to
      the "new clinical pathway." The goal of this investigation was to examine the
      impact of clinical pathways implementation on perioperative outcomes and
      institutional costs in patients undergoing total knee arthroplasty (TKA).
      METHODS: This before-and-after study evaluated patient clinical outcomes and
      economic costs after the implementation of institutional clinical pathway. The
      primary outcome was hospital length of stay (LOS). Clinical and economic outcomes
      were analyzed as continuous variables using paired t test. RESULTS: Fifty-four
      patients were identified for study inclusion. Patients undergoing their TKA after
      implementation of the clinical pathway had a significantly shorter hospital LOS
      (3.4 vs 4.4 days; P < 0.001). Patients reported significantly less postoperative
      pain, less postoperative confusion, and an easier time participating in physical
      therapy sessions after their second (after the clinical pathway implementation)
      TKA. Patients undergoing their TKA after the clinical pathway implementation had
      reduced total direct hospital costs ($956; 95% confidence interval, $233-$1785; P
      = 0.02). CONCLUSIONS: Our findings demonstrated that the use of a standardized
      clinical pathway reduced hospital LOS, improved clinical outcomes and patient
      satisfaction while reducing costs for identical surgical procedures.

PMID- 24121606
TI  - An analysis of the safety of epidural and spinal neuraxial anesthesia in more
      than 100,000 consecutive major lower extremity joint replacements.
AB  - BACKGROUND AND OBJECTIVES: A feared complication of spinal or epidural anesthesia
      is the development of epidural or spinal hematoma with subsequent neural element
      compression. Most available data are derived from the obstetric literature.
      Little is known about the frequency of hematoma occurrence among patients
      undergoing orthopedic joint arthroplasty, who are usually elderly and experience
      significant comorbidities. We sought to study the incidence of clinically
      significant lesions after spinal and epidural anesthesia and further describe
      their nature. METHODS: We retrospectively analyzed a database of all patients who
      underwent total hip or total knee arthroplasty under neuraxial anesthesia at our
      institution between January 2000 and October 2010. Patients with radiographically
      confirmed epidural lesions were identified and further analyzed. RESULTS: A total
      of 100,027 total knee and hip replacements under neuraxial anesthesia were
      performed at our institution. Ninety-seven patients underwent imaging studies to
      evaluate perioperative neurologic deficits (0.96/1000; 95% confidence interval,
      0.77-1.16/1000). Eight patients were identified with findings of an epidural
      blood or gas collection (0.07/1000; 95% confidence interval, 0.02-0.13/1000). No
      patients receiving only spinal anesthesia were affected. All patients diagnosed
      with hematoma took at least 1 drug that potentially impaired coagulation (5
      nonsteroidal anti-inflammatory agents, 1 a tricyclic antidepressant, and 1 an
      antiplatelet drug). No patient incurred persistent nerve damage. CONCLUSIONS: The
      incidence of epidural/spinal complications found in this consecutive case series
      is relatively low but higher than previously reported in the nonobstetric
      population. Further research using large data sets could quantify the
      significance of some of the potentially contributing factors observed in this
      study.

PMID- 24121607
TI  - Aberrant intrathecal pump refill: ultrasound-guided aspiration of a substantial
      quantity of subcutaneous hydromorphone.
AB  - Intrathecal drug delivery systems are an effective and increasingly common pain
      treatment modality for certain patient populations. Pumps are surgically inserted
      in a subcutaneous abdominal pocket and refilled with highly concentrated
      medication at regular intervals. Inadvertent injection of medication outside the
      pump is a known complication of the refill procedure. We describe the injection
      of hydromorphone into the pump's surrounding subcutaneous pocket, subsequent
      opioid overdose, and the novel application of ultrasound to visualize and
      aspirate the subcutaneous drug. Ultrasonography can be used as an effective
      modality for rapid diagnosis and treatment of an accidental pocket fill. 

PMID- 24121608
TI  - Adductor canal block versus femoral nerve block for analgesia after total knee
      arthroplasty: a randomized, double-blind study.
AB  - BACKGROUND AND OBJECTIVES: Femoral nerve block (FNB), a commonly used
      postoperative pain treatment after total knee arthroplasty (TKA), reduces
      quadriceps muscle strength essential for mobilization. In contrast, adductor
      canal block (ACB) is predominately a sensory nerve block. We hypothesized that
      ACB preserves quadriceps muscle strength as compared with FNB (primary end point)
      in patients after TKA. Secondary end points were effects on morphine consumption,
      pain, adductor muscle strength, morphine-related complications, and mobilization
      ability. METHODS: We performed a double-blind, randomized, controlled study of
      patients scheduled for TKA with spinal anesthesia. The patients were randomized
      to receive either a continuous ACB or an FNB via a catheter (30-mL 0.5%
      ropivacaine given initially, followed by a continuous infusion of 0.2%
      ropivacaine, 8 mL/h for 24 hours). Muscle strength was assessed with a handheld
      dynamometer, and we used the percentile change from baseline for comparisons. The
      trial was registered at clinicaltrials.gov (Identifier: NCT01470391). RESULTS: We
      enrolled 54 patients, of which 48 were analyzed. Quadriceps strength as a
      percentage of baseline was significantly higher in the ACB group compared with
      the FNB group: (median [range]) 52% [31-71] versus 18% [4-48], (95% confidence
      interval, 8-41; P = 0.004). There was no difference between the groups regarding
      morphine consumption (P = 0.94), pain at rest (P = 0.21), pain during flexion of
      the knee (P = 0.16), or adductor muscle strength (P = 0.39); neither was there a
      difference in morphine-related adverse effects or mobilization ability (P >
      0.05). CONCLUSIONS: Adductor canal block preserved quadriceps muscle strength
      better than FNB, without a significant difference in postoperative pain.

PMID- 24121609
TI  - Analgesia for clavicular fracture and surgery: a call for evidence.
AB  - The sensory innervation of the clavicle remains controversial. The
      supraclavicular, subclavian, and long thoracic/suprascapular nerves, alone or
      together, may be responsible for pain transmission after clavicular fracture and
      surgery. Peripheral nerve blocks used to anesthetize the clavicle include
      superficial cervical plexus blocks, interscalene blocks, and combined superficial
      cervical plexus-interscalene blocks. Future (randomized) trials are required to
      determine which constitutes the best option for emergency department (fracture)
      and operating room (surgical fixation) settings. 

PMID- 24121610
TI  - Ultrasound-guided sciatic nerve block in overweight and obese patients: a
      randomized comparison of performance time between the infragluteal and subgluteal
      space techniques.
AB  - BACKGROUND AND OBJECTIVES: Despite ultrasound (US) guidance, sciatic nerve block
      (SNB) remains among the least performed peripheral blocks. By targeting the
      tissue plane between the gluteus maximus and quadratus femoris muscles, the US
      guided subgluteal space technique may facilitate the performance of US-guided
      SNB. We aimed to evaluate whether the subgluteal space technique shortens SNB
      performance time in overweight and obese patients compared with the conventional
      infragluteal technique. METHODS: Overweight and obese patients (body mass index,
      > 25 kg m ) undergoing US-guided SNB for knee arthroplasty received 30 mL
      admixture (1:2 lidocaine 2%; bupivacaine 0.5% with 1:200,000 epinephrine) in the
      tissue plane between the gluteus maximus and quadratus femoris (subgluteal space
      group) or around the sciatic nerve at the infragluteal level (infragluteal
      group). All patients received spinal anesthesia, continuous femoral nerve block,
      and postoperative multimodal analgesia. The primary outcome was SNB performance
      time defined as the time interval between placement of the US transducer on skin,
      and needle withdrawal after injection. Number of needle passes, procedural pain,
      SNB-related complications, SNB success, postoperative pain, and opioid
      consumption were also assessed. RESULTS: Twenty-seven patients were assessed
      (subgluteal space, 14; infragluteal, 13). Mean SNB performance time was 4.4
      minutes (95% confidence interval, 3.7-5.0) for the subgluteal space group and 9.0
      minutes (95% confidence interval, 7.7-10.3) for the infragluteal group (P <
      0.0001). Number of needle passes and procedural pain scores were lower in the
      subgluteal space group. There were no differences in SNB success or analgesic
      outcomes. CONCLUSIONS: The subgluteal space technique may be performed 50%
      faster, with no detectable differences in block success and analgesic efficacy,
      compared with the infragluteal technique for US-guided SNB in overweight and
      obese patients receiving multimodal analgesia. Injection of local anesthetics
      along tissue planes may produce similar block characteristics to perineural
      injection for US-guided SNB.

PMID- 24121611
TI  - Comparison of anatomic landmarks and ultrasound guidance for intercostal nerve
      injections in cadavers.
AB  - BACKGROUND AND OBJECTIVES: Intercostal nerve (ICN) injections are routinely
      performed under anatomic landmark or fluoroscopic guidance for acute and chronic
      pain indications. Ultrasound (US) is being used increasingly to perform ICN
      injections, but there is lack of evidence to support categorically the benefits
      of US over conventional techniques. We compared guidance with US versus anatomic
      landmarks for accuracy and safety of ICN injections in cadavers in a 2-phase
      study that included evaluation of deposition of injected dye by dissection and
      spread of contrast on fluoroscopy. METHODS: A cadaver experiment was performed to
      validate US as an imaging modality for ICN blocks. In the first phase of the
      study, 12 ICN injections with 2 different volumes of dye were performed in 1
      cadaver using anatomic landmarks on one side and US-guidance on the other (6
      injections on each side). The cadaver was then dissected to evaluate spread of
      the dye. The second phase of the study consisted of 74 ICN injections (37 US
      guided and 37 using anatomic landmarks) of contrast dye in 6 non-embalmed
      cadavers followed by fluoroscopy to evaluate spread of the contrast dye. RESULTS:
      In the first phase of the study, the intercostal space was identified with US at
      all levels. Injection of 2 mL of dye was sufficient to ensure compete staining of
      the ICN for 5 of 6 US-guided injections but anatomic landmark guidance resulted
      in correct injection at only 2 of 6 intercostal spaces. No intravascular
      injection was found on dissection with either of the guidance techniques. In the
      second phase of the study, US-guidance was associated with a higher rate of
      intercostal spread of 1 mL of contrast dye on fluoroscopy compared with anatomic
      landmarks guidance (97% vs 70%; P = 0.017). CONCLUSIONS: Ultrasound confers
      higher accuracy and allows use of lower volumes of injectate compared with
      anatomic landmarks as a guidance method for ICN injections in cadavers.
      Ultrasound may be a viable alternative to anatomic landmarks as a guidance method
      for ICN injections.

PMID- 24121612
TI  - Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta
      casein locus in cloned cows.
AB  - Zinc-finger nickases (ZFNickases) are a type of programmable nuclease that can be
      engineered from zinc-finger nucleases to induce site-specific single-strand
      breaks or nicks in genomic DNA, which result in homology-directed repair.
      Although zinc-finger nuclease-mediated gene disruption has been demonstrated in
      pigs and cattle, they have not been used to target gene addition into an
      endogenous gene locus in any large domestic species. Here we show in bovine fetal
      fibroblasts that targeting ZFNickases to the endogenous beta-casein (CSN2) locus
      stimulates lysostaphin gene addition by homology-directed repair. We find that
      ZFNickase-treated cells can be successfully used in somatic cell nuclear
      transfer, resulting in live-born gene-targeted cows. Furthermore, the gene
      targeted cows secrete lysostaphin in their milk and in vitro assays demonstrate
      the milk's ability to kill Staphylococcus aureus. Our success with this strategy
      will facilitate new transgenic technologies beneficial to both agriculture and
      biomedicine. 

PMID- 24121614
TI  - A nopA deletion mutant of Sinorhizobium fredii USDA257, a soybean symbiont, is
      impaired in nodulation.
AB  - Sinorhizobium fredii USDA257 employs type III secretion system (T3SS) to deliver
      effector proteins into the host cells through pili. The nopA protein is the major
      component of USDA257 pili. The promoter region of USDA257 nopA possesses a well
      conserved tts box. Serial deletion analysis revealed that the tts box is
      absolutely essential for flavonoid induction of nopA. Deletion of nopA
      drastically lowered the number of nodules formed by USDA257 on cowpea and soybean
      cultivar Peking. In contrast to the parental strain, the USDA257 nopA mutant was
      able to form few nodules on soybean cultivars McCall and Williams 82. Light and
      transmission electron microscopy examination of these nodules revealed numerous
      starch grains both in the infected and uninfected cells.

PMID- 24121613
TI  - Diversity and bioprospective potential (cold-active enzymes) of cultivable marine
      bacteria from the subarctic glacial Fjord, Kongsfjorden.
AB  - The diversity and abundance of culturable bacteria in Kongsfjorden water (15
      stations) and sediments (12 stations) were studied. Viable numbers ranged between
      105-106 CFU l-1 in water and 102-104 CFU g-1 in the sediments. A total of 291 and
      43 bacterial isolates were retrieved from the water (KJF) and sediments (FS),
      respectively. Based on 16S rRNA gene sequence similarities, the KJF and FS
      isolates were grouped into 49 and 23 phylotypes, respectively. The KJF and FS
      phylotypes represented three phyla namely, Actinobacteria, Bacteroidetes, and
      Proteobacteria. At the genus level, Flavobacterium and Shewanella and at the
      species level, Pseudoaltermonas arctica and Colwellia psychrerythraea were
      dominant in the water and sediments, respectively. Most phylotypes were
      psychrotolerant with upper growth temperature limit of 25-37  degrees C and
      tolerated 0.3-2.5 M NaCl and pH values of 5.0-11.0. Majority of the phylotypes
      produced one or more of the extracellular hydrolytic enzymes amylase, lipase,
      caseinase, urease, gelatinase, and DNase at 4 and 18  degrees C, while none were
      chitinolytic. Few of the FS phylotypes exhibited extracellular activity only at 4
      or 18  degrees C. Nine FS and 21 KJF isolates were pigmented. The predominant
      cellular fatty acids were unsaturated, branched, and modified fatty acids, which
      are unique to cold-adapted bacteria.

PMID- 24121615
TI  - Differential radio-tolerance of nutrition-induced morphotypes of Deinococcus
      radiodurans R1.
AB  - Deinococcus radiodurans R1 is a highly radio-tolerant bacterium. Depending on the
      nutrient availability D. radiodurans R1 exists in three morphologies viz.
      monococcal, diplococcal and tetracoccal. In this study, we examined whether
      nutrition-induced morphotypes of D. radiodurans showed similar DNA damage upon
      gamma radiation exposure. Total DNA damage after radiation exposure was estimated
      by comparing percent double-strand breaks (DSBs) in genomic DNA. It was found
      that all three morphotypes exhibited different radiation tolerances which were
      also dependent on the radiation dose given. Monococcal forms were found to be
      most radio-tolerant at most of the tested radiation doses. Results showed that
      these nutrient-starved-condition induced morphotypes show lesser DNA DSBs upon
      irradiation, hence show higher radio-tolerance.

PMID- 24121616
TI  - Silica-coated gold nanoplates as stable photoacoustic contrast agents for
      sentinel lymph node imaging.
AB  - A biopsy of the first lymph node to which a tumor drains-the sentinel lymph node
      (SLN)-is commonly performed to identify micrometastases. Image guidance of the
      SLN biopsy procedure has the potential to improve its accuracy and decrease its
      morbidity. We have developed a new stable contrast agent for photoacoustic image
      guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit
      high photothermal stability when exposed to pulsed and continuous wave laser
      irradiation. This makes them well suited for in vivo photoacoustic imaging.
      Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs
      for SLN mapping in a mouse model where they exhibited a strong, sustained
      photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed
      that the Si-AuNPs quickly drain to the SLN, gradually spreading throughout a
      large portion of the node. 

PMID- 24121617
TI  - Determination of microbial extracellular enzyme activity in waters, soils, and
      sediments using high throughput microplate assays.
AB  - Much of the nutrient cycling and carbon processing in natural environments occurs
      through the activity of extracellular enzymes released by microorganisms. Thus,
      measurement of the activity of these extracellular enzymes can give insights into
      the rates of ecosystem level processes, such as organic matter decomposition or
      nitrogen and phosphorus mineralization. Assays of extracellular enzyme activity
      in environmental samples typically involve exposing the samples to artificial
      colorimetric or fluorometric substrates and tracking the rate of substrate
      hydrolysis. Here we describe microplate based methods for these procedures that
      allow the analysis of large numbers of samples within a short time frame. Samples
      are allowed to react with artificial substrates within 96-well microplates or
      deep well microplate blocks, and enzyme activity is subsequently determined by
      absorption or fluorescence of the resulting end product using a typical
      microplate reader or fluorometer. Such high throughput procedures not only
      facilitate comparisons between spatially separate sites or ecosystems, but also
      substantially reduce the cost of such assays by reducing overall reagent volumes
      needed per sample. 

PMID- 24121618
TI  - Mechanics and molecular filtration performance of graphyne nanoweb membranes for
      selective water purification.
AB  - Two-dimensional carbon materials such as the 2D nanoweb-like graphyne membrane
      are promising as molecular sieves for energy and environmental applications.
      Based on the application of water purification - the removal of contaminants from
      wastewater and seawater - here we use molecular dynamics (MD) simulations to
      investigate the interplay between mechanical forces, filtration mechanisms, and
      overall performance for graphyne membranes with different pore sizes. We carry
      out biaxial tensile tests and verify the superior mechanical robustness and
      tolerance of graphyne membranes against possible deformations from the membrane
      installation process. A possible ultimate stress in excess of 15 GPa and an
      ultimate strain of 1.2-2.7% are determined. We also demonstrate their excellent
      filtration performance with barrier-free water permeation and perfect rejection
      of the representative contaminants considered here, including divalent heavy
      metal salts (copper sulfate), hydrophobic organic chemicals (benzene and carbon
      tetrachloride), and inorganic monovalent salts (sodium chloride). We find that
      graphtriyne, with an effective pore diameter of 3.8 A, exhibits an optimal
      purification performance, because the contaminant rejection rate is more
      sensitive to pore size than water permeability. In addition, we find that the
      hydrophobic graphyne membranes exhibit higher rejection rates for hydrophilic
      contaminants compared to the hydrophobic ones. This size exclusion effect is a
      result of the larger hydrated radii of hydrophilic species due to stronger
      interactions between them and water molecules. Finally, we find that the maximum
      deformation of graphtriyne at the ultimate strain before material failure has
      only a minor impact on its filtration performance. One of the advantages of using
      graphyne for water purification is that no chemical functionalization or defects
      need to be introduced, which maintains the structural integrity of the membrane,
      and possibly, the long-term device performance. 

PMID- 24121620
TI  - In vivo evaluation of the kinematics of the long head of the biceps tendon within
      the pulley: a 3 T MRI motion analysis.
AB  - INTRODUCTION: To evaluate the kinetic amplitude and direction of the long head of
      the biceps tendon (LHB) within the pulley and the proximal bicipital groove, we
      performed a 3T-magnetic resonance-throwing motion analysis. MATERIALS AND
      METHODS: This prospective study was performed on a 3T-MRI scanner. A T2-weighted
      3D sequence in three specific positions of throwing motion of the dominant
      shoulder was performed under isometric 5 N loading conditions or without loading,
      respectively. Measurements were performed in high (140 degrees )
      abduction/external rotation, medium (110 degrees ) abduction/external rotation
      and low (45 degrees ) adduction-flexion/internal rotation. Multiplanar rotational
      reconstructions along the LHB in the bicipital groove allowed for the
      localization of the LHB including the degree of motion in the three most proximal
      slices. RESULTS: 12 healthy volunteers (age 22-34 years) were enrolled. Adduction
      led to an anterior deviation of the LHB within the bicipital groove. Loading
      conditions in medium (110 degrees ) elevation/external rotation furthermore led
      to a significant anterior deviation of the LHB. Conclusion Our findings support
      the thesis that pulley lesions result from movements of the LHB especially in
      extreme positions during throwing/overhead activities. Load application in the
      medium (110 degrees ) elevation/external rotation position might enable a better
      evaluation of patients with dedicated pulley lesions. These results need further
      evaluation in larger study cohorts and in patients with dedicated rotator cuff
      lesions, which will be the focus of ongoing studies.

PMID- 24121619
TI  - High prevalence of CYP2D6*41 (G2988A) allele in Saudi Arabians.
AB  - The main objective of this study was to evaluate CYP2D6 genetic polymorphism in a
      Saudi Arabian population by determining the frequencies of CYP2D6*41, CYP2D6*29,
      CYP2D6*3, CYP2D6*6 and CYP2D6*14 alleles. Genomic DNA was isolated from 192
      healthy Saudis representing different geographical regions, and genotyping of the
      selected CYP2D6 variants was carried out by direct sequencing. The allelic
      frequency of CYP2D6*41 was found to be 18.4%, and that of CYP2D6*29 to be 2.9%.
      The other investigated alleles were either not detected or rarely present in the
      study population. In addition, two commonly shared single nucleotide
      polymorphisms (SNPs) and two very rare SNPs among CYP2D6 alleles were detected.
      Further studies are therefore, required to evaluate the metabolic and clinical
      relevance of CYP2D6*41 in Saudi Arabians. 

PMID- 24121622
TI  - Remote cerebellar haemorrhage after lumbar spine surgery: case report.
AB  - Remote cerebellar haemorrhage (RCH) is a well-described complication of
      supratentorial surgical procedures with an incidence ranging between 0.2 and 4.9
      %, but is a rare complication of spinal surgery. We report a case of RCH in a 65
      year-old woman who showed sudden mental deterioration 48 h after lumbar spinal
      surgery, which was complicated by incidental dural tearing with minimal CSF loss.
      Brain CT scan revealed hypodense areas compatible with acute infarction involving
      mostly the left cerebellar hemisphere. No cerebral bleeding was observed. MRI was
      also performed revealing small cerebellar areas of acute infarction mainly
      relating the vermis and the left postero-inferior cerebellar hemisphere with
      haemorrhagic transformation and mass effect in the posterior fossa producing
      acute hydrocephalus. Haematoma removal was initially attempted by means of a
      suboccipital craniotomy. An external ventricular derivation was placed in a
      second procedure 24 h later due to the persistence of ventricular dilatation. At
      discharge the patient was only showing a slight dysmetria with the fine motor
      skills of hands and fingers. All cases of RCH after spinal surgery reported in
      the literature are invariably associated to iatrogenic dural tearing; although
      CSF loss seems to play the key role in the pathogenesis of this rare
      complication, the exact pathophysiology of this condition still remains
      undetermined.

PMID- 24121621
TI  - Comparative study of the closed reduction percutaneous  cannulated screw fixation
      and open reduction palmar locking  plate fixation in the treatment of AO type A2
      distal radius  fractures.
AB  - INTRODUCTION: The present study was designed to demonstrate the efficacy of
      standard 4.0 mm cannulated screw fixation by comparing it with palmar locking
      plate fixation in the treatment of acute, unstable, simple extra-articular distal
      radius fractures. MATERIALS AND METHODS: We prospectively collected and
      retrospectively analyzed outcomes data for 65 patients aged between 18 and 60
      with AO type A2 fractures treated with closed reduction, percutaneous cannulated
      screw fixation (CRPCS n = 34) or open reduction palmar locking plate fixation
      (ORPLP n = 31). Range of motion, grip strength, Gartland-Werley and QuickDASH
      scores were compared at 2 months after surgery, and final follow-up (mean 32
      months, range 12-90). Deterioration in radiographic parameters were measured and
      compared. Operative time and return to preinjury activity were evaluated.
      RESULTS: Parameters did not differ significantly between the groups at either
      time point with respect to grip strength or range of motion, except pronation and
      supination; they were better in the CRPCS group (p = 0.005 and 0.025,
      respectively) at 2 month follow-up. The Gartland-Werley and QuickDASH scores
      obtained at final follow-up were similar for each group and lacked statistical
      significance. Group comparison for the deterioration of radiologic parameters
      showed no significant difference. CRPCS group had significantly shorter operative
      time (p = 0.001) and there was no significant differences between the groups
      regarding the return to preinjury activity (p = 0.129). CONCLUSIONS: CRPCS group
      was found to be as successful as ORPLP group and it may be suitable in the case
      of young, active individuals with AO type A2 distal radius fractures.

PMID- 24121623
TI  - Subtrochanteric shortening osteotomy combined with cemented total hip
      arthroplasty for Crowe group IV hips.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a challenging surgical procedure that
      can be used to treat severely dislocated hips. There are few reports regarding
      cemented THAs involving subtrochanteric shortening osteotomy (SSO), even though
      cemented THAs provide great advantages because the femur is generally hypoplastic
      with a narrow, deformed canal. PURPOSES: We evaluated the utility of cemented THA
      with SSO for Crowe group IV hips, and assessed the relationship between leg
      lengthening and nerve injury. Our goal was to describe surgical techniques for
      optimizing surgical outcomes while minimizing the risk of nerve injury. METHODS:
      We retrospectively reviewed 34 cases of cemented THAs with transverse SSO for
      Crowe group IV. Prior to surgery, mean hip flexion was 93.1 degrees  (40 degrees 
      130 degrees ). The mean follow-up period was 5.2 years (3-10 years). RESULTS:
      Bone union took an average of 7.7 months (3-24 months). Mean leg lengthening was
      40.5 mm (15-70 mm) and was greater in patients without hip flexion contracture.
      None of the patients experienced any nerve injuries associated with leg
      lengthening, and radiographic evidence of loosening was not observed at the final
      follow-up. CONCLUSIONS: SSO combined with cemented THA is an effective treatment
      for severely dislocated hips. Leg lengthening is not necessarily associated with
      nerve injuries, and the likelihood of this surgical complication may be related
      to the presence of hip flexion contracture.

PMID- 24121624
TI  - Anterior screw fixation for an odontoid fracture using an Acutrak 4/5 screw: a
      case report.
AB  - The direct anterior screw fixation of odontoid fractures by a single cancellous
      screw, especially for osteoporotic vertebrae, has a potential risk of leading to
      insufficient stability and implant failures. We experienced good results
      following surgery using a single Acutrak 4/5 screw to obtain sufficient stability
      for an odontoid fracture in a patient with osteopenia. The screw is a cannulated
      self-tapping headless screw and has a tapered profile and full threads with
      variable pitches, and it can yield sufficient compression force as the screw is
      inserted. The preoperative severe neck pain of the patient was diminished
      immediately after the surgery. The patient achieved bone union in a short time
      and had a good clinical result for at least 3 years. Some biomechanical studies
      showed that the compression force of Acutrak standard screws was stronger than
      that of both 4.0-mm cancellous screws inserted with the lag screw technique and
      Herbert screws, and other studies showed that the compression force of Acutrak
      4/5 screws was equivalent to that of 4.5-mm cortical screws. However, there has
      been no clinical report of surgery using an Acutrak 4/5 screw for odontoid
      fractures. This is the first clinical report of fixation by an Acutrak 4/5 screw.

PMID- 24121625
TI  - The majority of patients with long-duration type 1 diabetes are insulin
      microsecretors and have functioning beta cells.
AB  - AIMS/HYPOTHESIS: Classically, type 1 diabetes is thought to proceed to absolute
      insulin deficiency. Recently developed ultrasensitive assays capable of detecting
      C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in
      patients with long-standing type 1 diabetes. It is not known whether this low
      level endogenous insulin secretion responds to physiological stimuli. We aimed to
      assess how commonly low-level detectable C-peptide occurs in long-duration type 1
      diabetes and whether it responds to a meal stimulus. METHODS: We performed a
      mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1
      diabetes, i.e. with age at diagnosis 16 (9-23) years (median [interquartile
      range]) and diabetes duration of 30 (19-41) years. We assessed fasting and
      stimulated serum C-peptide levels using an electrochemiluminescence assay
      (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio
      (UCPCR). RESULTS: Post-stimulation serum C-peptide was detectable at very low
      levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable
      serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n =
      11) in response to a meal, with no indication of levels falling (p < 0.0001).
      With increasing disease duration, absolute C-peptide levels fell although the
      numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with
      >30 years duration). Similar results were obtained for UCPCR.
      CONCLUSIONS/INTERPRETATION: Most patients with long-duration type 1 diabetes
      continue to secrete very low levels of endogenous insulin, which increase after
      meals. This is consistent with the presence of a small number of still functional
      beta cells and implies that beta cells are either escaping immune attack or
      undergoing regeneration.

PMID- 24121626
TI  - Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates
      their proliferation and protects against diabetes.
AB  - AIMS/HYPOTHESIS: Vascular endothelial growth factor (VEGF) has been recognised by
      loss-of-function experiments as a pleiotropic factor with importance in embryonic
      pancreas development and postnatal beta cell function. Chronic, nonconditional
      overexpression of VEGF-A has a deleterious effect on beta cell development and
      function. We report, for the first time, a conditional gain-of-function study to
      evaluate the effect of transient VEGF-A overexpression by adult pancreatic beta
      cells on islet vasculature and beta cell proliferation and survival, under both
      normal physiological and injury conditions. METHODS: In a transgenicmouse strain,
      overexpressing VEGF-A in a doxycycline-inducible and beta cell-specific manner,
      we evaluated the ability of VEGF-A to affect islet vessel density, beta cell
      proliferation and protection of the adult beta cell mass from toxin-induced
      injury. RESULTS: Short-term VEGF-A overexpression resulted in islet
      hypervascularisation, increased beta cell proliferation and protection from toxin
      mediated beta cell death, and thereby prevented the development of
      hyperglycaemia. Extended overexpression of VEGF-A led to impaired glucose
      tolerance, elevated fasting glycaemia and a decreased beta cell mass.
      CONCLUSIONS/INTERPRETATION: Overexpression of VEGF-A in beta cells time
      dependently affects glycometabolic control and beta cell protection and
      proliferation. These data nourish further studies to examine the role of
      controlled VEGF delivery in (pre)clinical applications aimed at protecting and/or
      restoring the injured beta cell mass.

PMID- 24121627
TI  - Functional investigation of transmembrane helix 3 in H+-translocating
      pyrophosphatase.
AB  - H+-translocating pyrophosphatase (H+-PPase, EC 3.6.1.1) plays an important role
      in acidifying vacuoles by transporting protons across membranes at the expense of
      pyrophosphate (PP(i)) hydrolysis. Vigna radiata H+-PPase (VrH+-PPase) contains 16
      transmembrane helices (TMs). The hydrophobicity of TM3 is relatively lower than
      that of most other TMs, and the amino acids in this TM are highly conserved in
      plants. Furthermore, TM5 and -6, which are the core TMs involving in H+-PPase
      functions, are near TM3. It is thus proposed that TM3 is associated with H+-PPase
      activity. To address this possibility, site-directed mutagenesis was applied in
      this investigation to determine the role of TM3 in VrH+-PPase. Upon
      alanine/serine substitution, T138 and S142, whose side chains face toward the
      center TMs, were found to be involved in efficient proton transport. G149/S153
      and G160/A164 pairs at the crucial termini of the two GxxxG-like motifs are
      indispensable in maintaining enzymatic activities and conformational stability.
      Moreover, stability in the vicinity surrounding G149 is pivotal for efficient
      expression. S153, M161 and A164 are critical for the K+-mediated stimulation of
      H+-PPase. Taken together, our results demonstrate that TM3 plays essential roles
      in PP(i) hydrolysis, proton transport, expression, and K+ stimulation of H+
      PPase.

PMID- 24121628
TI  - Theoretical calculation of bending stiffness of alveolar wall.
AB  - The bending stiffness of the alveolar wall is theoretically analyzed in this
      study through analytical modeling. First, the alveolar wall facet and its
      characteristics were geometrically simplified and then modeled using known
      physical laws. Bending stiffness is shown to be dependent on alveolar wall
      thickness, density, Poisson's ratio and speed of the longitudinal wave. The
      normal bending stiffness of the alveolar wall was further determined. For the
      adult human, the normal bending stiffness is calculated to be 71.0-414.7 nNm,
      while for the adult mouse it is 1.9-30.0 nNm. The results of this study can be
      used as a reference for future pulmonary emphysema and fibrosis studies, as the
      bending stiffness of alveolar wall will be lower and higher, respectively; than
      the theoretically determined normal values.

PMID- 24121629
TI  - Reductive dechlorination of tetrachlorobisphenol A by Pd/Fe bimetallic catalysts.
AB  - The Pd/Fe bimetallic catalysts of micron sizes were synthesized and the rates of
      tetrachlorobisphenol A (TCBPA) degradation were measured under various conditions
      using a batch reactor system. The results showed that TCBPA was rapidly
      dechlorinated to tri-, di- and mono-chlorobisphenol A and to bisphenol A (BPA).
      The observed rate constants (k(obs)) were found to increase as functions of the
      Pd coverage on the Fe particles and the dosages of the catalysts within the
      reactors. The k(obs) value decreased as the initial TCBPA concentration
      increased, suggesting that the TCBPA dechlorination may follow a surface-site
      limiting Langmuir-Hinshelwood rate model. The weakly acidic solution, especially
      at or near pH 6.0, also favored the dechlorination of TCBPA. At pH 6.0, Pd
      coverage of 0.04 4 wt% and catalyst dosage of 5 g L(-1), TCBPA with an initial
      concentration of 20 MUM was completely transformed within 60 min, and BPA was
      detected as the major product through the reaction time. Meanwhile, the k(obs)
      values measured at constant solution pH correlated linearly with the mass of
      particle-bound Pd introduced to the reactors, regardless of Pd/Fe catalyst dosage
      or Pd surface coverage. This study suggested that Pd/Fe catalysts could be
      potentially employed to rapidly degrade TCBPA in the contaminated environment.

PMID- 24121630
TI  - Biotransformation of Direct Blue 1 by a moderately halophilic bacterium
      Marinobacter sp. strain HBRA and toxicity assessment of degraded metabolites.
AB  - The ability of halophiles to survive in the extreme salt concentrations has
      gained them the importance of being used in the treatment of industrial waste
      waters. A moderately halophilic bacterial strain with the ability to degrade the
      complex azo dye Direct Blue-1 (DB-1) was isolated from sea water and identified
      as Marinobacter sp. strain HBRA. Complete decolorization of DB-1 (100 mg L(-1))
      was achieved in 6h at 37  degrees C, pH 8 and with 70 g L(-1) NaCl.
      Decolorization was analyzed by UV-vis spectrophotometer. The FT-IR spectrum
      revealed that Marinobacter sp. strain HBRA specifically targeted azo bond (NN) at
      1631 cm(-1) to break down Direct Blue-1. Formation of metabolites at different
      retention times in HPLC indicated degradation. Biotransformation pathway for DB-1
      was proposed based on LC-MS. Phytotoxicity study revealed the less toxic nature
      of the metabolites compared to the dye. Genotoxicity with Allium cepa confirmed
      the cytotoxic nature of DB-1 by inducing several chromosomal abnormalities
      compared to the negligible effects of degraded metabolites. The current study is
      the first report on the detoxification of DB-1 by Marinobacter sp. strain HBRA.

PMID- 24121632
TI  - Selective photoredox using graphene-based composite photocatalysts.
AB  - Graphene (GR) has proven to be a promising candidate to construct effective GR
      based composite photocatalysts with enhanced catalytic activities for solar
      energy conversion. During the past few years, various GR-based composite
      photocatalysts have been developed and applied in a myriad of fields. In this
      perspective review, compared with the traditional applications of GR-based
      nanocomposites for the "non-selective" degradation of pollutants, photo
      deactivation of bacteria and water splitting to H2 and O2, we mainly focus on the
      recent progress in the applications of GR-based composite photocatalysts for
      "selective" organic transformations, including reduction of CO2 to renewable
      fuels, reduction of nitroaromatic compounds to amino compounds, oxidation of
      alcohols to aldehydes and acids, epoxidation of alkenes, hydroxylation of phenol,
      and oxidation of tertiary amines. The different roles of GR in these GR-based
      nanocomposite photocatalysts such as providing a photoelectron reservoir and
      performing as an organic dye-like macromolecular photosensitizer have been
      summarized. In addition, graphene oxide (GO) as a co-catalyst in GO-organic
      species photocatalysts and GO itself as a photocatalyst for selective reduction
      of CO2 have also been demonstrated. Finally, perspectives on the future research
      direction of GR-based composite photocatalysts toward selective organic redox
      transformations are discussed and it is clear that there is a wide scope of
      opportunities awaiting us in this promising research field. 

PMID- 24121631
TI  - Sortilin, a novel APOE receptor implicated in Alzheimer disease.
AB  - In the brain, apolipoprotein E (APOE) delivers cholesterol-rich lipoproteins to
      neurons to support synaptogenesis and maintenance of synaptic connections. Three
      APOE alleles exist in the human population with epsilon4 being an Alzheimer
      disease (AD) risk gene and epsilon2 being protective relative to the common
      epsilon3 variant. Many hypotheses have been advanced concerning allele-specific
      effects of APOE on neurodegeneration including effects on Abeta clearance,
      synaptic transmission, or neurotoxicity. Central to most proposed APOE functions
      is its interaction with receptors that mediate cellular uptake of this ligand.
      Several members of the LDL receptor gene family have been implicated as APOE
      receptors in the (patho)physiology of APOE in the brain, yet their specific modes
      of action in AD remain controversial. Recently, the pro-neurotrophin receptor
      sortilin has been identified as a novel APOE receptor in neurons. Ablation of
      sortilin expression in mice results in accumulation of APOE and Abeta in the
      brain. Moreover, primary neurons lacking sortilin exhibit significantly impaired
      uptake of APOE/Abeta complexes. Despite increased brain APOE levels, sortilin
      deficient animals recapitulate anomalies in brain lipid homeostasis seen in APOE
      null mice, indicating functional deficiency in APOE uptake pathways. Taken
      together, these findings suggest a link between Abeta catabolism and pro
      neurotrophin signaling converging on this receptor pathway. 

PMID- 24121633
TI  - HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression
      of CHRNA1 pre-mRNA.
AB  - CHRNA1 gene, encoding the muscle nicotinic acetylcholine receptor alpha subunit,
      harbors an inframe exon P3A. Inclusion of exon P3A disables assembly of the
      acetylcholine receptor subunits. A single nucleotide mutation in exon P3A
      identified in congenital myasthenic syndrome causes exclusive inclusion of exon
      P3A. The mutation gains a de novo binding affinity for a splicing enhancing RNA
      binding protein, hnRNP LL, and displaces binding of a splicing suppressing RNA
      binding protein, hnRNP L. The hnRNP L binds to another splicing repressor PTB
      through the proline-rich region and promotes PTB binding to the polypyrimidine
      tract upstream of exon P3A, whereas hnRNP LL lacking the proline-rich region
      cannot bind to PTB. Interaction of hnRNP L with PTB inhibits association of
      U2AF(65) and U1 snRNP with the upstream and downstream of P3A, respectively,
      which causes a defect in exon P3A definition. HnRNP L and hnRNP LL thus
      antagonistically modulate PTB-mediated splicing suppression of exon P3A.

PMID- 24121635
TI  - Synthesis of a metal-free coordinating ring via formation of a cleavable
      [2]catenane.
AB  - We describe an efficient methodology which allows for the preparation of a
      macrocycle incorporating a free coordination site. It is based on a transition
      metal-templated strategy and RCM to provide access to a Cu(I)-complexed
      [2]catenane consisting of the desired cyclised compound and a cleavable ring.
      Release of the cleavable ring leads to the formation of the target macrocycle in
      quantitative yield.

PMID- 24121634
TI  - Evidence for distinct human auditory cortex regions for sound location versus
      identity processing.
AB  - Neurophysiological animal models suggest that anterior auditory cortex (AC) areas
      process sound identity information, whereas posterior ACs specialize in sound
      location processing. In humans, inconsistent neuroimaging results and
      insufficient causal evidence have challenged the existence of such parallel AC
      organization. Here we transiently inhibit bilateral anterior or posterior AC
      areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while
      subjects listen to Reference/Probe sound pairs and perform either sound location
      or identity discrimination tasks. The targeting of TMS pulses, delivered 55-145
      ms after Probes, is confirmed with individual-level cortical electric-field
      estimates. Our data show that TMS to posterior AC regions delays reaction times
      (RT) significantly more during sound location than identity discrimination,
      whereas TMS to anterior AC regions delays RTs significantly more during sound
      identity than location discrimination. This double dissociation provides direct
      causal support for parallel processing of sound identity features in anterior AC
      and sound location in posterior AC. 

PMID- 24121636
TI  - Catalytic regeneration of mercury sorbents.
AB  - Traditionally, mercury sorbents are disposed of in landfills, which may lead to
      contamination of soil and groundwater. In this work, the regeneration of
      activated carbon (AC) as a mercury sorbent was investigated. The decomposition of
      HgCl2 on the surface of pure AC was studied, as well as sorbent which has been
      treated with FeCl3 or NaCl. In all cases, the sorbent is found to be structurally
      stable through a single regeneration, which is verified through BET, XRD, and XPS
      analysis. The desorption of mercury from the sorbent is found to follow Henry's
      law. Additionally, a kinetic analysis suggests that although the presence of
      activated carbon lowers the energy requirement for the desorption of mercury, it
      significantly decreases the rate by decreasing the concentration of the HgCl2.
      FeCl3 and NaCl both promoted the decomposition of HgCl2, but FeCl3 did so more
      significantly, increasing the rate constants by a factor of 10 and decreasing the
      activation energy for the decomposition of HgCl2 by 14% to 40%. 

PMID- 24121637
TI  - Effects of nanoscale zero-valent iron particles on biological nitrogen and
      phosphorus removal and microorganisms in activated sludge.
AB  - The use of nanoscale zero-valent iron (NZVI) particles in environmental
      remediation and wastewater treatment has recently increased. The effects of NZVI
      on nitrogen and phosphorus removal were examined under continuous
      aerobic/anaerobic conditions by employing activated sludge. NZVI did not display
      any measurable effect on nitrogen removal at the concentration of 50mg/L and
      below. However, 200mg/L of NZVI inhibited NH4(+)-N removal. The addition of NZVI
      at 20mg/L and above significantly (p<0.05) improved the phosphorous removal. The
      microbial activities were inhibited upon exposure to NZVI according to the ATP
      and reactive oxygen species (ROS) results. In comparison to control, the ATP
      content decreased by around 13%, 31% and 43% at the NZVI doses of 20, 50, and
      200mg/L, respectively, probably due to ROS production under NZVI exposure.
      Lactate dehydrogenase (LDH) release assay suggested that NZVI concentration of
      200mg/L cast adverse effects on microorganisms. Interestingly, lower
      concentrations of NZVI (20 and 50mg/L) boosted the dehydrogenase activity;
      however, approximately 19% depression in dehydrogenase activity was detected at
      200mg/L. The high throughput 16S rDNA pyrosequencing results indicated that
      uncultured bacterial genera Sinobacteraceae, Xanthomonadaceae, Alcaligenaceae and
      Propionivibrio were sensitive to NZVI particles. 

PMID- 24121638
TI  - Removal of lindane from an aqueous solution by using aminopropyl silica gel
      immobilized calix[6]arene.
AB  - An aminopropyl silica gel-immobilized calix[6]arene (C[6]APS) has been used for
      the removal of lindane from an aqueous solution in batch sorption technique. The
      C[6]APS was synthesized with p-tert-butylcalix[6]arene hexacarboxylate derivative
      and aminopropyl silica gel in the presence of N,N'-diisopropyl carbodiimide
      coupling reagent. The sorption study was carried out as functions of solution pH,
      contact time, initial lindane concentration, C[6]APS dosage and ionic strength of
      solution. The matrix effect of natural water samples on the sorption efficiency
      of C[6]APS was also investigated. Maximum lindane removal was obtained at a wide
      pH range of 2-8 and sorption equilibrium was achieved in 2h. The isotherm
      analysis indicated that the sorption data can be represented by both Langmuir and
      Freundlich isotherm models. Increasing ionic strength of the solutions increased
      the sorption efficiency and matrix of natural water samples had no effect on the
      sorption of lindane. By using multilinear regression model, regression equation
      was also developed to explain the effects of the experimental variables. 

PMID- 24121639
TI  - Removal of priority pollutants from water by means of dielectric barrier
      discharge atmospheric plasma.
AB  - Two different nonthermal plasma reactors at atmospheric pressure were assessed
      for the removal of organic micropollutants (atrazine, chlorfenvinfos, 2,4
      dibromophenol, and lindane) from aqueous solutions (1-5 mg L(-1)) at laboratory
      scale. Both devices were dielectric barrier discharge (DBD) reactors; one was a
      conventional batch reactor (R1) and the other a coaxial thin-falling-water-film
      reactor (R2). A first-order degradation kinetics was proposed for both
      experiments. The kinetic constants (k) were slightly faster in R1 (0.534 min(-1)
      for atrazine; 0.567 min(-1) for chlorfenvinfos; 0.802 min(-1) for 2,4
      dibromophenol; 0.389 min(-1) for lindane) than in R2 (0.104 min(-1) for atrazine;
      0.523 min(-1) for chlorfenvinfos; 0.273 min(-1) for 2,4-dibromophenol; 0.294 min(
      1) for lindane). However, energy efficiencies were about one order of magnitude
      higher in R2 (89 mg kW(-1) h(-1) for atrazine; 447 mg kW(-1) h(-1) for c
      hlorfenvinfos; 47 mg kW(-1) h(-1) for 2,4-dibromophenol; 50 mg kW(-1) h(-1) for
      lindane) than in R1. Degradation by -products of all four compounds were
      identified in R1. As expected, when the plasma treatment (R1) was applied to
      industrial wastewater spiked with atrazine or lindane, micropollutant removal was
      also achieved, although at a lower rate than with aqueous solutions (k = 0.117
      min(-1) for atrazine; k = 0.061 min(-1) for lindane).

PMID- 24121640
TI  - Investigation of the impacts of ethyl lactate based Fenton treatment on soil
      quality for polycyclic aromatic hydrocarbons (PAHs)-contaminated soils.
AB  - This study aims to investigate the impacts of ethyl lactate (EL) based Fenton
      treatment on soil quality for polycyclic aromatic hydrocarbons (PAHs)
      contaminated soils. Accumulation of oxygenated-polycyclic aromatic hydrocarbons
      (oxy-PAHs) was observed, but quantitative measurement on the most abundant
      compound 9,10-anthraquinone (ATQ) showed lower accumulation of the compound than
      that reported for ethanol (ET) based Fenton treatment. In general, as compared to
      conventional water (CW) based Fenton treatment, the EL based Fenton treatment
      exerted either a lower or higher negative impact on soil physicochemical
      properties depending on the property type and shared the main disadvantage of
      reduced soil pH. For revegetation, EL based Fenton treatment was most
      appropriately adopted for soil with native pH >/~ 6.2 in order to obtain a final
      soil pH >/~ 4.9 subject to the soil buffering capacity.

PMID- 24121641
TI  - Mobilization and re-adsorption of arsenate on ferrihydrite and hematite in the
      presence of oxalate.
AB  - In this study, mobilization and re-adsorption of arsenate on 2-line ferrihydrite
      and hematite in the presence of oxalate was investigated. Our results showed that
      arsenate could be mobilized during the dissolution of ferrihydrite and hematite.
      After reaching the maximum values, the released arsenate could re-adsorb on the
      residual ferrihydrite, whereas such an observation was not significant in
      hematite system. More reactive sites exposed during the dissolution of
      ferrihydrite could contribute to the re-adsorption of the released arsenate at pH
      3.0, while the insignificant re-adsorption of arsenate on hematite could be
      explained by the inhibitory adsorption effect of oxalate on arsenate. Although
      dissolution rates of iron oxides decreased with the increase of arsenate on both
      ferrihydrite and hematite, dissolution rate was mainly determined by the
      reactivity of iron oxides, and ferrihydrite showed a higher reactivity than
      hematite in the presence of oxalate. Mathematic model proposed in our study
      further indicated that arsenate loading showed a more significant effect on
      arsenate mobilization in hematite system, while it was more effective in arsenate
      re-adsorption in ferrihydrite system. 

PMID- 24121642
TI  - Electrochemical reactor with rotating cylinder electrode for optimum
      electrochemical recovery of nickel from plating rinsing effluents.
AB  - This study is devoted to analyze the metallic electrochemical recovery of nickel
      from synthetic solutions simulating plating rinsing discharges, in order to meet
      the water recycling policies implemented in these industries. These effluents
      present dilute Ni(II) concentrations (100 and 200 ppm) in chloride and sulfate
      media without supporting electrolyte (397-4202 MUS cm(-1)), which stems poor
      current distribution, limited mass transfer, ohmic drops and enhancement of
      parasitic reactions. An electrochemical reactor with rotating cylinder electrode
      (RCE) and a pH controller were utilized to overcome these problems. The pH
      control around 4 was crucial to yield high purity nickel, and thus prevent the
      precipitation of hydroxides and oxides. Macroelectrolysis experiments were
      systematically conducted to analyze the impacts of the applied current density in
      the recovery efficiency and energy consumption, particularly for very diluted
      effluents (100 and 200 ppm Ni(II)), which present major recovery problems.
      Promising nickel recoveries in the order of 90% were found in the former baths
      using a current density of -3.08 mA cm(-2), and with overall profits of 9.64 and
      14.69 USD kg(-1), respectively. These estimations were based on the international
      market price for nickel ($18 USD kg(-1)).

PMID- 24121643
TI  - Transcriptional profile of tomato roots exhibiting Bacillus thuringiensis-induced
      resistance to Ralstonia solanacearum.
AB  - KEY MESSAGE: Activation of SA-dependent signaling pathway and suppression of JA
      dependent signaling pathway seem to play key roles inB. thuringiensis-induced
      resistance toR. solanacearumin tomato plants. Bacillus thuringiensis, a well
      known and effective bio-insecticide, has attracted considerable attention as a
      potential biological control agent for the suppression of plant diseases.
      Treatment of tomato roots with a filter-sterilized cell-free filtrate (CF) of B.
      thuringiensis systemically suppresses bacterial wilt caused by Ralstonia
      solanacearum through systemic activation of the plant defense system. Comparative
      analysis of the expression of the Pathogenesis-Related 1(P6) gene, a marker for
      induced resistance to pathogens, in various tissues of tomato plants treated with
      CF on their roots suggested that the B. thuringiensis-induced defense system was
      activated in the leaf, stem, and main root tissues, but not in the lateral root
      tissue. At the same time, the growth of R. solanacearum was significantly
      suppressed in the CF-treated main roots but not in the CF-treated lateral roots.
      This distinct activation of the defense reaction and suppression of R.
      solanacearum were reflected by the differences in the transcriptional profiles of
      the main and lateral tissues in response to the CF. In CF-treated main roots, but
      not CF-treated lateral roots, the expression of several salicylic acid (SA)
      responsive defense-related genes was specifically induced, whereas jasmonic acid
      (JA)-related gene expression was either down-regulated or not induced in response
      to the CF. On the other hand, genes encoding ethylene (ET)-related proteins were
      induced equally in both the main and lateral root tissues. Taken together, the co
      activation of SA-dependent signaling pathway with ET-dependent signaling pathway
      and suppression of JA-dependent signaling pathway may play key roles in B.
      thuringiensis-induced resistance to R. solanacearum in tomato.

PMID- 24121644
TI  - Analysis of sequence repeats of proteins in the PDB.
AB  - Internal repeats in protein sequences play a significant role in the evolution of
      protein structure and function. Applications of different bioinformatics tools
      help in the identification and characterization of these repeats. In the present
      study, we analyzed sequence repeats in a non-redundant set of proteins available
      in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a
      protein, PDBeFOLD for assessing structural similarity, PDBsum for finding
      functional involvement and Pfam for domain assignment of the repeats in a
      protein. Through the analysis of sequence repeats, we found that identity of the
      sequence repeats falls in the range of 20-40% and, the superimposed structures of
      the most of the sequence repeats maintain similar overall folding. Analysis
      sequence repeats at the functional level reveals that most of the sequence
      repeats are involved in the function of the protein through functionally involved
      residues in the repeat regions. We also found that sequence repeats in single and
      two domain proteins often contained conserved sequence motifs for the function of
      the domain. 

PMID- 24121645
TI  - Methods for performing crosses in Setaria viridis, a new model system for the
      grasses.
AB  - Setaria viridis is an emerging model system for C4 grasses. It is closely related
      to the bioenergy feed stock switchgrass and the grain crop foxtail millet.
      Recently, the 510 Mb genome of foxtail millet, S. italica, has been sequenced
      (1,2) and a 25x coverage genome sequence of the weedy relative S. viridis is in
      progress. S. viridis has a number of characteristics that make it a potentially
      excellent model genetic system including a rapid generation time, small stature,
      simple growth requirements, prolific seed production (3) and developed systems
      for both transient and stable transformation (4). However, the genetics of S.
      viridis is largely unexplored, in part, due to the lack of detailed methods for
      performing crosses. To date, no standard protocol has been adopted that will
      permit rapid production of seeds from controlled crosses. The protocol presented
      here is optimized for performing genetic crosses in S. viridis, accession A10.1.
      We have employed a simple heat treatment with warm water for emasculation after
      pruning the panicle to retain 20-30 florets and labeling of flowers to eliminate
      seeds resulting from newly developed flowers after emasculation. After testing a
      series of heat treatments at permissive temperatures and varying the duration of
      dipping, we have established an optimum temperature and time range of 48  degrees
      C for 3-6 min. By using this method, a minimum of 15 crosses can be performed by
      a single worker per day and an average of 3-5 outcross progeny per panicle can be
      recovered. Therefore, an average of 45-75 outcross progeny can be produced by one
      person in a single day. Broad implementation of this technique will facilitate
      the development of recombinant inbred line populations of S. viridis X S. viridis
      or S. viridis X S. italica, mapping mutations through bulk segregant analysis and
      creating higher order mutants for genetic analysis. 

PMID- 24121646
TI  - Perceptions of age and brain in relation to hearing help-seeking and
      rehabilitation.
AB  - OBJECTIVES: This study used a qualitative approach to explore the perspectives of
      adults with hearing impairment on hearing help-seeking and rehabilitation. Two
      superordinate themes, Age and Brain, emerged from prior analyses and are
      investigated in the present article. DESIGN: In-depth semistructured interviews
      were completed in four countries with 34 adults (aged 26 to 96 years) with
      hearing impairment. Participants were asked to "Tell the story of your hearing."
      Participants included individuals with different levels of experiences in hearing
      help-seeking and rehabilitation. The themes of Age and Brain emerged from the
      data based on qualitative content analysis. These major themes were analyzed
      further using interpretative phenomenology to create models of themes and
      subthemes as they related to hearing help-seeking and rehabilitation expectations
      and experience. RESULTS: Age was discussed by 68% of the 34 participants. The
      data were sorted into three themes: Expectations, Self-Image, and Ways of Coping.
      Brain was discussed by 50% of the participants. The data were sorted into three
      themes: Cognitive Operations, Plasticity, and Mental Effort. CONCLUSIONS: Adults
      with hearing impairment think of their age and their brain as contributing to
      their hearing impairment, disability, help-seeking, and rehabilitation. Although
      hearing impairment associated with older age was typically construed as a stigma,
      not all perceptions of aging and hearing impairment were negative. Some
      participants viewed older age and its influence on relationships or priorities as
      a reason for seeking out hearing health care or as the determining factor in
      deciding to wear hearing aids (HAs). Some expected hearing impairment with older
      age, thus they found it easier to accept wearing HAs than they may have at a
      younger age. They discussed the brain in terms of the cognitive operations that
      may either inhibit or improve speech communication. Participants believed that
      they could train their brains to improve their communication (and sometimes avoid
      the need for HAs) or to increase their HA benefit. Age and Brain interconnected
      in a number of ways. Participants believed that older age led to cognitive
      decline, which resulted in decreased speech understanding. Participants also
      believed that the cognitive decline that accompanies older age may limit HA
      benefit. Hearing healthcare providers may wish to clarify negative messages about
      age and brain with their patients and provide information about how older brains
      are capable of changing and benefiting from HA use and comprehensive audiologic
      rehabilitation programs.

PMID- 24121647
TI  - Effective masking levels for 500 and 2000 Hz bone conduction auditory steady
      state responses in infants and adults with normal hearing.
AB  - OBJECTIVES: Few studies have investigated effective masking levels (EMLs) needed
      to isolate the test ear for bone conduction assessments in infants. The objective
      of this study was to determine EMLs for 500 and 2000 Hz bone conduction auditory
      steady state responses (ASSRs) to amplitude (AM)/frequency-modulated (FM) stimuli
      for infants and adults with normal hearing. Maturational factors that contribute
      to infant-adult differences in EMLs will also be investigated. The present study
      and previously published 1000 and 4000 Hz EML data will be compared to
      investigate EML across four frequencies. These findings will provide a starting
      point for implementing clinical masking for infant bone conduction testing using
      physiological measures. DESIGN: Participants were 15 infants (7 to 35 weeks) and
      15 adults (21 to 56 years) with normal hearing. Bone-conducted single ASSR
      stimuli (research MASTER) were 100% AM and 25% FM at 85 and 101 Hz for 500 and
      2000 Hz carrier frequencies, respectively. They were presented at 25 and 35 dB HL
      for 500 Hz and at 35 and 45 dB HL for 2000 Hz for both infants and adults
      (approximately 10 and 20 dB SL at each frequency for infants). Air-conducted
      narrowband maskers were presented to both ears simultaneously. Real-ear to
      coupler differences were measured to account for differences in the sound
      pressure developed in infant and adult ear canals as a result of ear-canal size.
      Data analyses were conducted for mean EMLs across frequency (500 to 4000 Hz) and
      between age groups. Masked and unmasked ASSR amplitudes were compared for 500 and
      2000 Hz. RESULTS: Both infants and adults required much more masking (25 to 33
      dB) to eliminate responses at 500 compared with 2000 Hz. On average, infants
      required 16 dB more masking at 500 Hz and similar amounts of masking at 2000 Hz
      compared with adults. When adjusted for ear-canal size and bone conduction
      sensitivity, the pattern of results did not change. Across all four frequencies,
      infants showed a systematic decrease in mean EMLs with an increase in frequency;
      all pair-wise comparisons were significant except 2000 versus 4000 Hz. Adults
      showed smaller frequency-dependent changes in EML (only significantly greater for
      500 versus 2000 Hz and 4000 Hz). When ear-canal size and bone conduction
      sensitivity were taken into account, only 500 Hz required more masking than other
      frequencies in infants; there were no significant frequency-dependent trends for
      adults, although the greater EMLs at 1000 versus 2000 Hz and 4000 Hz approached
      significance. Unmasked and masked amplitudes tended to be larger for 2000 Hz but
      not for 500 Hz when comparing infants with adults. CONCLUSIONS: EMLs appropriate
      for infants for bone conduction ASSRs elicited to AM/FM stimuli are considerably
      higher at 500 compared with 2000 Hz. Infants also need more masking at 500 Hz
      compared with adults but the same amount of masking at 2000 Hz. Comparisons
      across four frequencies reveal a systematic decrease in EML with an increase in
      frequency in infants, which is not apparent in adults. Recommended EMLs for AM/FM
      bone-conducted ASSR stimuli presented at 35 dB HL for 500, 1000, 2000, and 4000
      Hz, respectively, are: (1) infants: 81, 68, 59, and 45 dB SPL, and (2) adults:
      66, 63, 59, and 55 dB SPL.

PMID- 24121649
TI  - 2-(1-(2-Benzhydrylnaphthylimino)ethyl)pyridylnickel halides: synthesis,
      characterization, and ethylene polymerization behavior.
AB  - A series of 2-(1-(2-benzhydrylnaphthylimino)ethyl)pyridine derivatives (L1-L3)
      was synthesized and fully characterized. The organic compounds acted as bi
      dentate ligands on reacting with nickel halides to afford two kinds of nickel
      complexes, either mononuclear bis-ligated L2NiBr2 (Ni1-Ni3) or chloro-bridged
      dinuclear L2Ni2Cl4 (Ni4-Ni6) complexes. The nickel complexes were fully
      characterized, and the single crystal X-ray diffraction revealed for Ni2, a
      distorted square pyramidal geometry at nickel comprising four nitrogens of two
      ligands and one bromide; whereas for Ni4, a centrosymmetric dimer possessing a
      distorted octahedral geometry at nickel was formed by two nitrogens of one
      ligand, two bridging chlorides and one terminal chloride along with oxygen from
      methanol (solvent). When activated with diethylaluminium chloride (Et2AlCl), all
      nickel complexes performed with high activities (up to 1.22 * 10(7) g (PE) mol(
      1) (Ni) h(-1)) towards ethylene polymerization; the obtained polyethylene
      possessed high branching, low molecular weight and narrow polydispersity,
      suggestive of a single-site active species. The effect of the polymerization
      parameters, including the nature of the ligands/halides on the catalytic
      performance is discussed. 

PMID- 24121648
TI  - Spatial separation benefit for unaided and aided listening.
AB  - OBJECTIVES: The benefit attributable to spatial separation of speech and noise
      was measured as a function of low-pass cutoff frequency with and without
      bilateral hearing aids. DESIGN: Fourteen younger and 10 older adults with normal
      hearing and 12 older adults with mild-to-moderate sloping high frequency hearing
      loss were included to assess the effects of age and hearing loss. Subjects with
      hearing loss were provided commercially available bilateral hearing aids.
      Consonant recognition was measured at 70 dB SPL in a background of speech-shaped
      noise at 66 dB SPL. Speech and noise were low-pass filtered at 1.7, 3.4, and 7.1
      kHz. Nonsense syllables were always at 0 degrees  and noise was at either 0
      degrees  or 90 degrees . Speech and noise spectra for all conditions were
      digitally recorded using a probe microphone placed in each ear canal of each
      subject. Spectra and levels of speech, and quiet thresholds for narrowband
      noises, were used to calculate the Articulation Index and provide predictions of
      unaided and aided (hearing-impaired only) consonant recognition, spatial benefit,
      and hearing aid benefit for each condition. Subjective ratings of workload (NASA
      Task Load Index) were obtained for all unaided and aided measures of speech
      recognition. RESULTS: Consonant recognition in noise improved for all groups with
      speech and noise spatially separated and with the addition of high-frequency
      speech information. Scores were poorer overall for the older adults with hearing
      loss than for the other groups. For normal-hearing subjects, observed scores and
      spatial benefit were better than predicted. For hearing-impaired subjects, scores
      did not significantly improve with hearing aids, even with higher frequencies and
      spatial separation, and were poorer than predicted especially for aided
      listening. Similar to subjects with normal hearing, spatial benefit for hearing
      impaired subjects was larger than predicted. CONCLUSIONS: Younger and older
      adults with normal hearing benefited from spatial separation of speech and noise
      sources to a greater extent than predicted based on simple audibility. Thus, no
      age-related deficits in the use of interaural difference cues were observed.
      Although hearing aid benefit was negligible, perceived listening effort was lower
      aided than unaided, especially with spatial separation. Articulation Index
      predictions revealed that speech audibility was generally restored with hearing
      aids across a wide bandwidth of speech, especially in the far ear. Thus, reduced
      audibility was not a primary factor in limited hearing aid benefit, suggesting
      that peripheral, central-auditory and/or cognitive changes may have played a
      role. In contrast, unaided and aided spatial benefit was better than predicted,
      and spatial benefit was slightly larger with hearing aids than without. Thus,
      these older adults with hearing loss using bilateral hearing aids were able to
      take advantage of binaural cues to improve consonant recognition in noise.

PMID- 24121650
TI  - A novel chemiluminescence assay of mitoxantrone based on diperiodatocuprate(III)
      oxidation.
AB  - A novel and strong chemiluminescence (CL) of luminol with diperiodatocuprate
      (K5[Cu(HIO6)2]) was observed in alkaline medium. After the addition of
      mitoxantrone (MTX) into this system, the CL intensity could be greatly inhibited
      by MTX. Based on the phenomenon, a sensitive CL method was established for
      analysis of MTX combining with flow injection technology. Under optimum
      experimental conditions, the CL intensity was linearly related to the logarithm
      concentration of MTX from 5.0*10(-9)-1.0*10(-7) g/ml with the detection limit of
      1.1*10(-9) g/ml (S/N=3). The relative standard deviation was 1.2% for 5.0*10(-8)
      g/ml of MTX. The proposed method was successfully applied for determination of
      MTX in pharmaceutical preparations and biological fluids. The possible CL
      reaction mechanism was also discussed briefly.

PMID- 24121651
TI  - Theoretical studies on the electronic structures and photoelectron spectra of tri
      rhenium oxide clusters: Re3O(n)(-) and Re3O(n) (n=1-6).
AB  - Density functional theory (DFT) calculations are performed to study the
      structural and electronic properties of tri-rhenium oxide clusters Re3On(-/0)
      (n=1-6). Generalized Koopmans' theorem is applied to predict the vertical
      detachment energies (VDEs) and simulate the photoelectron spectra (PES).
      Theoretical calculations at the B3LYP level are carried out to search for the
      global minima for both the anions and the neutrals. For the anions, the first two
      O atoms prefer the same corner position of a Re3 triangle. Whereas, Re3O3(-)
      possesses a C2v symmetry with one bridging and two terminal O atoms. The next
      three O atoms (n=4-6) are adding sequentially on the basis of Re3O3(-) motif,
      i.e., adding one terminal O atom for Re3O4(-), one terminal and one bridging O
      atoms for Re3O5(-), and one terminal and two bridging O atoms for Re3O6(-),
      respectively. Their corresponding neutral species are similar to the anions in
      geometry except Re3O4 and Re3O5. Molecular orbital analyses are employed to
      investigate the chemical bonding and structural evolution in these tri-rhenium
      oxide clusters.

PMID- 24121652
TI  - The vibration characterization of synthetic crystalline lead hydrogen arsenite
      chloride precipitates Pb2(HAsO3)Cl2-implications of solidification of As (III)
      and Pb (II).
AB  - The lead hydrogen arsenite chloride precipitates (Pb2(HAsO3)Cl2) are synthesized
      hydrothermally due to its structure trap for lead and arsenic. The synthetic
      precipitates have well-developed crystalline. The crystals of lead hydrogen
      arsenite chloride have a series of obvious IR bands at 790, 721, 645, 589 and 554
      cm(-1). These bands are assigned to the Ag mode of As-O stretching vibration
      (790), the antisymmetric stretch of As-OH (721), Ag modes (554 and 589) and E1g
      (645) of the symmetric deformation (nu1 and nu3) of AsO3 unit. The Raman bands at
      782, 723, 586, 559 cm(-1) are attributed to As-O stretching vibration (nu1) and
      the symmetric deformation (nu1 and nu3), of which the positions and assignments
      display in accordance with IR result. The most intense Raman band is found in 814
      cm(-1) and is attributed to the Ag mode of nu1 symmetric stretching vibration of
      AsO3 unit, which is not active in IR. The SEM image shows that the precipitates
      have needle morphology.

PMID- 24121653
TI  - Pathological endoplasmic reticulum stress mediated by the IRE1 pathway
      contributes to pre-insulitic beta cell apoptosis in a virus-induced rat model of
      type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We hypothesised that pathological endoplasmic reticulum (ER)
      stress contributes to beta cell death during development of type 1 diabetes. In
      this study, we investigated the occurrence of beta cell ER stress and the
      signalling pathways involved during discrete stages of autoimmune diabetes
      progression. The virus-inducible BBDR rat model was used to systematically
      interrogate the three main ER stress signalling pathways (IRE1 [inositol
      requiring protein-1], PERK [double-stranded RNA-dependent protein kinase (PKR)
      like ER kinase] and ATF6 [activating transcription factor 6]) in pancreatic beta
      cells during type 1 diabetes development. METHODS: ER stress and apoptotic
      markers were assessed by immunoblot analyses of isolated pancreatic islets and
      immunofluorescence staining of pancreas sections from control and virus-induced
      rats. Various time points were analysed: (1) early stages preceding the
      development of insulitis and (2) a late stage during onset and progression of
      insulitis, which precedes overt hyperglycaemia. RESULTS: The IRE1 pathway,
      including its downstream component X-box-binding protein 1, was specifically
      activated in pancreatic beta cells of virus-induced rats at early stages
      preceding the development of insulitis. Furthermore, ER stress-specific pro
      apoptotic caspase 12 and effector caspase 3 were also activated at this stage.
      Activation of PERK and its downstream effector pro-apoptotic CHOP (CCAAT/
      enhancer-binding-protein homologous protein), only occurred during late stages of
      diabetes induction concurrent with insulitis, whereas ATF6 activation in
      pancreatic beta cells was similar in control and virus-induced rats.
      CONCLUSIONS/INTERPRETATION: Activation of the IRE1 pathway and ER stress-specific
      pro-apoptotic caspase 12, before the development of insulitis, are indicative of
      ER stress-mediated beta cell damage. The early occurrence of pathological ER
      stress and death in pancreatic beta cells may contribute to the initiation and/or
      progression of virus-induced autoimmune diabetes.

PMID- 24121654
TI  - The sagA/pel locus does not regulate the expression of the M protein of the M1T1
      lineage of group A Streptococcus.
AB  - Altered expression of Group A Streptococcus (GAS) virulence factors, including
      the M protein, can result as a consequence of spontaneous genetic changes that
      occur during laboratory and animal passage. Occurrence of such secondary
      mutations during targeted gene deletion could confound the interpretation of
      effects attributable to the function of the gene being investigated.
      Contradicting reports on whether the sagA/pel locus regulates the M protein
      encoding emm might be due to inconsistent occurrence of mutations unrelated with
      sagA. This study examined the possibility that altered emm expression observed in
      association with sagA/pel deletion mutants is artifactual. sagA deletion mutants
      (MGAS2221DeltasagA) of M1T1 isolate MGAS2221 obtained using liquid broth for GAS
      growth during the deletion process had diminished emm transcription and no
      detectable M protein production. In contrast, a DeltasagA mutant of another
      closely genetically related M1T1 isolate had normal emm expression. The sagB gene
      does not regulate emm; however, one of three MGAS2221DeltasagB mutants had
      diminished emm expression. The emm regulator mga was downregulated in these M
      protein expression-negative strains. These results argue that sagA deletion does
      not directly cause the downregulation of emm expression. Indeed, two
      MGAS2221DeltasagA mutants obtained using agar plates for GAS growth during the
      deletion process both had normal emm expression. We conclude that the sagA/pel
      locus does not regulate emm expression in the M1T1 lineage and provide a protocol
      for targeted gene deletion that we find less prone to the generation of mutants
      exhibiting downregulation in emm expression. 

PMID- 24121655
TI  - Single-incision technique for the internal fixation of distal fractures of the
      tibia and fibula: a combined anatomic and clinical study.
AB  - OBJECTIVES: To present a novel single anterior-lateral approach for the treatment
      of distal tibia and fibula fracture via anatomical study and primary clinical
      application in order to minimize soft tissue complications. DESIGN: Both a gross
      anatomic cadaver and retrospective studies of the single-incision technique in
      patients recruited between June 2004 and January 2010. SETTING: Level I trauma
      center. PATIENTS/PARTICIPANTS: Twenty-six legs of 14 adult human cadavers and
      clinical recruitment of 49 patients (29 males, 20 females) with a mean age of
      37.6 years (range 11-68) with fracture of distal 1/3 tibia and fibula.
      INTERVENTION: A single anterior-lateral incision technique for open reduction and
      internal fixations of distal tibia and fibula fractures. MAIN OUTCOME MEASURES:
      To identify the anatomic structures at risk in the anterolateral aspect of the
      lower leg and explicit the safe dissection distance from the extensor digitorum
      longus (EDL) to tibia and fibula, 26 legs of 14 adult human embalmed specimens
      were recruited in the anatomical study with the distance between the EDL and the
      anterior edge of the distal thirds of the tibia, as well as the distance between
      the EDL and the anterior edge of the distal thirds of the fibula were measured,
      and their mutual relationships to the surrounding anatomical structures
      described. Mean average standard deviations were also calculated. As for the
      clinical study, the quality of bone union and soft tissue healing were noted.
      RESULTS: The mean distances between the distal tibia and the EDL were measured to
      be 2.96 +/- 0.46 cm (proximal), 1.85 +/- 0.25 cm (middle), and 2.15 +/- 0.30 cm
      (distal), and that between the fibula and the EDL were 1.82 +/- 0.28 cm
      (proximal), 2.09 +/- 0.31 cm (middle), and 2.30 +/- 0.27 cm (distal), which means
      the safe gap from the distal tibia to EDL was 1.6-3.4 cm and from the EDL to
      fibula was 1.5-2.6 cm. The anterior tibial vein and artery and the deep fibular
      nerve lie on the anterior interosseous membrane over the lateral surface of the
      distal tibia were excellently visualized. Review of clinical outcomes in 49
      patients with combined distal tibial and fibular fractures who underwent
      reduction and fixation with the single-incision technique, revealed uneventful
      fracture healings in 47 patients; and two cases of superficial wound necrosis
      which were treated and healed in 4 months. There was no case of delayed union or
      non-union. CONCLUSION: Distal fibula fracture occurring with distal tibia
      fracture poses a challenge for stable fixation. This has necessitated the need
      for dual incisions on the distal leg to approach each fracture for reduction and
      fixation. However, a single anterolateral incision enables the safe approach to
      the lateral aspects of the distal tibia and fibula thus eliminating the need for
      two separate incisions and minimizing the soft tissue complication to some
      extent. Meanwhile, the neurovascular bundle at risk during operation, distal
      tibia and fibula is clearly exposed in the single anterior-lateral incision.

PMID- 24121656
TI  - Temperature-dependent piezoresistivity in an MWCNT/epoxy nanocomposite
      temperature sensor with ultrahigh performance.
AB  - A temperature sensor was fabricated from a polymer nanocomposite with multi
      walled carbon nanotube (MWCNT) as nanofiller (i.e., MWCNT/epoxy). The electrical
      resistance and temperature coefficient of resistance (TCR) of the temperature
      sensor were characterized experimentally. The effects of temperature (within the
      range 333-373 K) and MWCNT content (within the range 1-5 wt%) were investigated
      thoroughly. It was found that the resistance increases with increasing
      temperature and decreasing MWCNT content. However, the resistance change ratio
      related to the TCR increases with increasing temperature and MWCNT content. The
      highest value of TCR (0.021 K(-1)), which was observed in the case of 5 wt%
      MWCNT, is much higher than those of traditional metals and MWCNT-based
      temperature sensors. Moreover, the corresponding numerical simulation-conducted
      to explain the above temperature-dependent piezoresistivity of the nanocomposite
      temperature sensor-indicated the key role of a temperature-dependent tunneling
      effect. 

PMID- 24121657
TI  - Evaluating participatory decision processes: which methods inform reflective
      practice?
AB  - Evaluating participatory decision processes serves two key purposes: validating
      the usefulness of specific interventions for stakeholders, interveners and
      funders of conflict management processes, and improving practice. However,
      evaluation design remains challenging, partly because when attempting to serve
      both purposes we may end up serving neither well. In fact, the better we respond
      to one, the less we may satisfy the other. Evaluations tend to focus on
      endogenous factors (e.g., stakeholder selection, BATNAs, mutually beneficial
      tradeoffs, quality of the intervention, etc.), because we believe that the
      success of participatory decision processes hinges on them, and they also seem to
      lend themselves to caeteris paribus statistical comparisons across cases. We
      argue that context matters too and that contextual differences among specific
      cases are meaningful enough to undermine conclusions derived solely from
      comparisons of process-endogenous factors implicitly rooted in the caeteris
      paribus assumption. We illustrate this argument with an environmental mediation
      case. We compare data collected about it through surveys geared toward
      comparability across cases to information elicited through in-depth interviews
      geared toward case specifics. The surveys, designed by the U.S. Institute of
      Environmental Conflict Resolution, feed a database of environmental conflicts
      that can help make the (statistical) case for intervention in environmental
      conflict management. Our interviews elicit case details - including context -
      that enable interveners to link context specifics and intervention actions to
      outcomes. We argue that neither approach can "serve both masters." 

PMID- 24121658
TI  - Process evaluation for a school-based physical activity intervention for 6th- and
      7th-grade boys: reach, dose, and fidelity.
AB  - The purpose was to evaluate the reach, dose, and fidelity of Guys Only Activity
      for Life (G.O.A.L.), a 7-week pilot intervention conducted from February to March
      2011 to increase 6th and 7th grade boys' moderate-to-vigorous physical activity
      (MVPA). One middle school was randomly assigned to the G.O.A.L. intervention and
      another from the same urban school district in the Midwestern U.S. to a
      comparison condition. Thirty boys, ages 10-14 years, participated in each school.
      The intervention, guided by the Health Promotion Model (HPM) and Self
      Determination Theory (SDT), consisted of a 90-min after-school physical activity
      club 4 days/week and one motivational interviewing session with a registered
      (school) nurse. Data were gathered via attendance records, club observations,
      heart rate monitors, audio-taping of motivational interviewing sessions, and
      surveys. On average boys attended the club 2.11 days/week (SD=.86). A trained
      independent process evaluator reported that the physical activity club
      instructors provided the boys with the opportunity for a mean of 25.8 min/day of
      MVPA. Using a four-point Likert scale (1=disagree a lot; 4=agree a lot), the
      process evaluator perceived that the club was delivered with high fidelity and
      adherence to the underlying theories (M=3.48; SD=0.39). Sessions with the nurse
      lasted an average of 13 min, 29 s. All boys attended. Two trained independent
      coders indicated that the nurse demonstrated at least beginning proficiency for
      all tasks associated with motivational interviewing, with the exception of using
      sufficient open- as opposed to closed-ended questions and reflections compared to
      questions. Fidelity related to session delivery and adherence to the theories was
      high (M=3.83; SD=0.19). The process evaluation data indicated that strategies are
      needed to increase attendance and boys' MVPA during the club time.

PMID- 24121660
TI  - Insights into tetracycline adsorption onto goethite: experiments and modeling.
AB  - The surface adsorption behavior of tetracycline (TC), a zwitterionic antibiotic,
      to goethite was investigated as a function of pH, ionic strength and TC
      concentration using batch adsorption experiments and structural information was
      derived from attenuated total reflectance Fourier transform infrared spectrum
      observations. The spectroscopic results suggested that the tricarbonylamide group
      and the phenolic diketone group of the TC molecule were involved in interacting
      with the goethite surface depending on the pH level. A charge distribution
      surface complexation model was developed to describe the macroscopic adsorption
      trends. Two inner-sphere surface complexation species could successfully describe
      observed adsorption trends: under acidic condition TC may interact with the
      surface of goethite, forming a monodentate complex through the tricarbonylamide
      group, while under alkaline condition forming a more stable bidentate complex via
      the tricarbonylamide and phenolic diketone groups. The model could well predict
      the adsorption behavior of TC under a relatively wide range of pH, ionic strength
      and surface coverage. However, since the model did not fully consider the
      molecular size of TC, the model might overestimate the adsorption when TC surface
      coverage is higher than 1.42 MUmol m(-2).

PMID- 24121659
TI  - Lack of prion transmission by sexual or parental routes in experimentally
      infected hamsters.
AB  - Prion diseases are a group of neurodegenerative disorders affecting humans as
      well as captive and wild animals. The mechanisms and routes governing the natural
      spread of prions are not completely understood and several hypotheses have been
      proposed. In this study, we analyzed the effect of gender in prion incubation
      period, as well as the possibility of prion transmission by sexual and parental
      contact using 263K infected hamsters as a model. Our results show that males have
      significantly longer incubation periods compared with females when exposed to the
      same quantity of infectious material. Importantly, no evidence of sexual or
      parental prion transmission was found, even 500 d after sexual contact or birth,
      respectively. Western blotting and PMCA were unable to detect sub-clinical levels
      of PrP(Sc) in experimental subjects, suggesting a complete absence of prion
      transmission by these routes. Our results show that sexual and parental
      transmission of prions does not occur in this model. It remains to be studied
      whether this conclusion is valid also for other prion strains and species. 

PMID- 24121661
TI  - Application of the Multi-Attribute Value Theory for engaging stakeholders in
      groundwater protection in the Vosvozis catchment in Greece.
AB  - Multi-Attribute Value Theory (MAVT) was used to investigate stakeholders'
      preferences and beliefs in ameliorating a deteriorating ecosystem, i.e. Vosvozis
      River and Ismarida Lake in Northeastern Greece. Various monetary and
      environmental criteria were evaluated with scores and weights by different
      stakeholder groups and key individuals such as farmers, fishermen, entrepreneurs,
      residents and ecologists to elicit their preferences concerning alternative
      protection scenarios. The ultimate objective was to propose policy
      recommendations for a sustainable water resources management for the case study
      area. The analysis revealed an overwhelming agreement among stakeholders
      regarding the dire need for immediate actions in order to preserve and enhance
      Vosvozis ecosystem. With a two stage evaluation process, the MAVT analysis led to
      a high consensus among the stakeholders on the alternative that favors water
      recycling from the wastewater treatment plant combined with small dams for
      rainwater harvesting. 

PMID- 24121662
TI  - Introduction and feasibility assessment of laundry use of recycled water in dual
      reticulation systems in Australia.
AB  - Laundry is a potential new end use of recycled water in dual reticulation
      systems. Generally, the community is willing to accept this new end use if it can
      meet the concerns on health issues, durability of washing machine, cloth quality
      and aesthetic appearance. This study addresses all these major concerns thereby
      assisting in the introduction and promotion of this new end use in the existing
      and proposed dual reticulation systems. Five representative cloth materials were
      selected for washing in tap water and in recycled water for up to 50 wash cycles
      for comparative studies. The tearing/tensile strength tests were used for the
      assessment of cloth durability. ANOVA one way test was applied for the
      significance analysis (Tukey's test p<0.05) which indicated that there is no
      significant change in the tensile/tearing strengths of washed cloth samples.
      Scanning electron microscope (SEM) images of the washed cloth samples found no
      distinct change in surface morphology. Textile colour analysis (CIEDE2000)
      analysed the variation in colour of the washed cloth samples and showed that the
      change in colour ?E ranges from 0-1 revealing no visible difference in colour of
      cloth samples. Langelier Saturation Index (LSI) was used as the indicator for
      predicting corrosive/scaling potential of recycled water. The LSI values ranged
      from +0.5 to -0.5, indicating no corrosive or scaling potential of recycled
      water. The microbiological study of the cloth samples washed in recycled water
      indicated that there was no contamination with representative bacteria. As the
      recycled water has similar effects like tap water on cloth and washing machine,
      it is safe to use for laundry. 

PMID- 24121664
TI  - EZH2 takes the stage when BRCA1 loses.

PMID- 24121665
TI  - The interaction of molybdenum pentachloride with O- and S-heterocycles.
AB  - The 1 : 2 molar reactions of MoCl5, in dichloromethane at room temperature, with
      tetrahydrofuran (thf), tetrahydropyran (thp), dioxane and tetrahydrothiophene
      (tht) afforded, respectively, [Mo(O)Cl3(thf)]2, 1, and MoCl4(L)2 (L = thp, 2;
      dioxane, 3; tht, 4), in 81-87% yields. The molecular structures of 1, 2 and 4
      were ascertained by X-ray diffractometry. DFT and spectroscopic (IR, NMR) studies
      were carried out in order to shed light on thermodynamic and kinetic aspects of
      the reaction pathways. 

PMID- 24121663
TI  - GLS2 is transcriptionally regulated by p73 and contributes to neuronal
      differentiation.
AB  - The amino acid Glutamine is converted into Glutamate by a deamidation reaction
      catalyzed by the enzyme Glutaminase (GLS). Two isoforms of this enzyme have been
      described, and the GLS2 isoform is regulated by the tumor suppressor gene p53.
      Here, we show that the p53 family member TAp73 also drives the expression of
      GLS2. Specifically, we demonstrate that TAp73 regulates GLS2 during retinoic acid
      induced terminal neuronal differentiation of neuroblastoma cells, and
      overexpression or inhibition of GLS2 modulates neuronal differentiation and
      intracellular levels of ATP. Moreover, inhibition of GLS activity, by removing
      Glutamine from the growth medium, impairs in vitro differentiation of cortical
      neurons. Finally, expression of GLS2 increases during mouse cerebellar
      development. Although, p73 is dispensable for the in vivo expression of GLS2,
      TAp73 loss affects GABA and Glutamate levels in cortical neurons. Together, these
      findings suggest a role for GLS2 acting, at least in part, downstream of p73 in
      neuronal differentiation and highlight a possible role of p73 in regulating
      neurotransmitter synthesis. 

PMID- 24121666
TI  - Hypotonic regulation of mouse epithelial sodium channel in Xenopus laevis
      oocytes.
AB  - The regulation of the epithelial Na+ channel (ENaC) during cell swelling is
      relevant in cellular processes in which cell volume changes occur, i.e.,
      migration, proliferation and cell absorption. Its sensitivity to hypotonically
      induced swelling was investigated in the Xenopus oocyte expression system with
      the injection of the three subunits of mouse ENaC. We used voltage-clamp
      techniques to study the amiloride-sensitive Na+ currents (INa(amil)) and video
      microscopic methodologies to assess oocyte volume changes. Under conditions of
      mild swelling (25 % reduced hypotonicity) inward current amplitude decreased
      rapidly over 1.5 min. In contrast, there was no change in current amplitude of
      H2O-injected oocytes to the osmotic insult. INa(amil) kinetics analysis revealed
      a decrease in the slower inactivation time constant during the hypotonic stimuli.
      Currents from ENaC-injected oocytes were not sensitive to external Cl- reduction.
      Neither short- nor long-term cytochalasin D treatment affected the observed
      response. Oocytes expressing a DEG mutant beta-ENaC subunit (beta-S518K) with an
      open probability of 1 had reduced INa(amil) hypotonic response compared to
      oocytes injected with wild-type ENaC subunits. Finally, during the hypotonic
      response ENaC-injected oocytes did not show a cell volume difference compared
      with water-injected oocytes. On this basis we suggest that hypotonicity-dependent
      ENaC inhibition is principally mediated through an effect on open probability of
      channels in the membrane.

PMID- 24121668
TI  - Size-controlled fluorescent nanodiamonds: a facile method of fabrication and
      color-center counting.
AB  - We present a facile method for the production of fluorescent diamond nanocrystals
      (DNCs) of different sizes and efficiently quantify the concentration of emitting
      defect color centers (DCCs) of each DNC size. We prepared the DNCs by ball
      milling commercially available micrometer-sized synthetic (high pressure, high
      temperature (HPHT)) diamonds and then separated the as-produced DNCs by density
      gradient ultracentrifugation (DGU) into size-controlled fractions. A protocol to
      enhance the uniformity of the nitrogen-vacancy (NV) centers in the diamonds was
      devised by depositing the DNCs as a dense monolayer on amino-silanized silicon
      substrates and then subjecting the monolayer to He(+) beam irradiation. Using a
      standard confocal setup, we analyzed the average number of NV centers per
      crystal, and obtained a quantitative relationship between the DNC particle size
      and the NV number per crystal. This relationship was in good agreement with
      results from previous studies that used more elaborate setups. Our findings
      suggest that nanocrystal size separation by DGU may be used to control the number
      of defects per nanocrystal. The efficient approaches described herein to control
      and quantify DCCs are valuable to researchers as they explore applications for
      color centers and new strategies to create them. 

PMID- 24121667
TI  - CDK5 is essential for TGF-beta1-induced epithelial-mesenchymal transition and
      breast cancer progression.
AB  - Epithelial-mesenchymal transition is a change of cellular plasticity critical for
      embryonic development and tumor metastasis. CDK5 is a proline-directed
      serine/threonine kinase playing important roles in cancer progression. Here we
      show that CDK5 is commonly overexpressed and significantly correlated with
      several poor prognostic parameters of breast cancer. We found that CDK5
      participated in TGF-beta1-induced EMT. In MCF10A, TGF-beta1 upregulated the CDK5
      and p35 expression, and CDK5 knockdown inhibited TGF-beta1-induced EMT. CDK5
      overexpression also exhibited a potential synergy in promoting TGF-beta1-induced
      EMT. In mesenchymal breast cancer cells MDA-MB-231 and BT549, CDK5 knockdown
      suppressed cell motility and tumorigenesis. We further demonstrated that CDK5
      modulated cancer cell migration and tumor formation by regulating the
      phosphorylation of FAK at Ser-732. Therefore, CDK5-FAK pathway, as a downstream
      step of TGF-beta1 signaling, is essential for EMT and motility in breast cancer
      cells. This study implicates the potential value of CDK5 as a molecular marker
      for breast cancer.

PMID- 24121669
TI  - Accuracy of oxygen tissue saturation values in assessing severity in patients
      with sepsis admitted to emergency departments.
AB  - INTRODUCTION: Near-infrared spectrometry assesses hemoglobin saturation of oxygen
      in tissues (StO2). Although it may provide additional information on local
      microcirculation function, the usefulness of near-infrared spectrometry in septic
      patients is debated. This study evaluated whether baseline StO2 value is useful
      in septic patients admitted to the emergency department with a diagnosis of
      severe sepsis. MATERIALS AND METHODS: We carried out a prospective multicenter
      study in three emergency departments in Paris, France. Triage nurses were to
      record StO2, the results were blinding to the emergency physicians. Patients were
      eligible when presenting with at least two of the following parameters:
      temperature higher than 38 degrees C or less than 36 degrees C, respiratory rate
      greater than 30/min, heart rate greater than 120/min, and systolic arterial blood
      pressure less than 110 mmHg. Patients with a final diagnosis of sepsis and severe
      sepsis were analyzed. RESULTS: We analyzed 98 patients (70 with sepsis and 28
      with severe sepsis). Thirty-day mortality was 2.9 versus 14.3% (P=0.048) in the
      sepsis and the severe sepsis group, respectively. No significant difference in
      the median StO2 was observed in patients with sepsis and severe sepsis [79% (74
      85%) vs. 77% (72-83%), respectively; P=0.66]. The area under the curve of the
      receiver operating characteristic curve for StO2 to predict severe sepsis was
      0.53 (0.39-0.66; P=0.5) and the cutoff value was 77%. Median StO2 did not differ
      in patients admitted to the ICU [80% (60-88%) vs. 79% (74-84%); P=0.78] and in
      nonsurvivors compared with that of survivors [79% (74-85%) vs. 76% (73-83%);
      P=0.64]. CONCLUSION: This study fails to show any value of StO2 baseline at
      triage for early detection of severe sepsis in emergency patients.

PMID- 24121670
TI  - Effects of Zn2+ and Pb2+ dopants on the activity of Ga2O3-based photocatalysts
      for water splitting.
AB  - Zn-doped and Pb-doped beta-Ga2O3-based photocatalysts were prepared by an
      impregnation method. The photocatalyst based on the Zn-doped beta-Ga2O3 shows a
      greatly enhanced activity in water splitting while the Pb-doped beta-Ga2O3 one
      shows a dramatic decrease in activity. The effects of Zn(2+) and Pb(2+) dopants
      on the activity of Ga2O3-based photocatalysts for water splitting were
      investigated by HRTEM, XPS and time-resolved IR spectroscopy. A ZnGa2O4-beta
      Ga2O3 heterojunction is formed in the surface region of the Zn-doped beta-Ga2O3
      and a slower decay of photogenerated electrons is observed. The ZnGa2O4-beta
      Ga2O3 heterojunction exhibits type-II band alignment and facilitates charge
      separation, thus leading to an enhanced photocatalytic activity for water
      splitting. Unlike Zn(2+) ions, Pb(2+) ions are coordinated by oxygen atoms to
      form polyhedra as dopants, resulting in distorted surface structure and fast
      decay of photogenerated electrons of beta-Ga2O3. These results suggest that the
      Pb dopants act as charge recombination centers expediting the recombination of
      photogenerated electrons and holes, thus decreasing the photocatalytic activity. 

PMID- 24121672
TI  - In situ atomic imaging of coalescence of Au nanoparticles on graphene: rotation
      and grain boundary migration.
AB  - Using in situ transmission electron microscopy, we demonstrated that gold
      nanoparticles are unified via "oriented attachment" assisted either by
      nanoparticle rotation or grain boundary migration at the attachment interface. We
      also observed that the combined nanoparticle changes shape with stable facet
      planes via surface diffusion, along with recrystallization. 

PMID- 24121671
TI  - A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during
      tumour treatment better than an annexin V-based probe.
AB  - OBJECTIVES: Molecular imaging of apoptosis is frequently discussed for monitoring
      cancer therapies. Here, we compare the low molecular weight phosphatidylserine
      targeting ligand zinc2+-dipicolylamine (Zn2+-DPA) with the established but
      reasonably larger protein annexin V. METHODS: Molecular apoptosis imaging with
      the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn2+-DPA (794
      nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups
      were investigated: untreated controls and treated tumours after 1 or 4 days of
      anti-angiogenic therapy (SU11248). Additionally, MUPET with 18 F-FDG was
      performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and
      validated by quantitative immunohistochemistry. RESULTS: Compared with untreated
      control tumours, TUNEL staining indicated significant apoptosis after 1 day (P <
      0.05) and 4 days (P < 0.01) of treatment. Concordantly, Zn2+-DPA uptake increased
      significantly after 1 day (P < 0.05) and 4 days (P < 0.01). Surprisingly, annexin
      V failed to detect significant differences between control and treated animals.
      Contrary to the increasing uptake of Zn2+-DPA, 18 F-FDG tumour uptake decreased
      significantly at days 1 (P < 0.05) and 4 (P < 0.01). CONCLUSIONS: Increase in
      apoptosis during anti-angiogenic therapy was detected significantly better with
      the low molecular weight probe Zn2+-DPA than with the annexin V-based probe.
      Additionally, significant treatment effects were detectable as early using Zn2+
      DPA as with measurements of the glucose metabolism using 18 F-FDG. KEY POINTS: *
      The detection of apoptosis by non-invasive imaging is important in oncology. * A
      new low molecular weight probe Zn2+-DPA shows promise in depicting anti
      angiogenic effects. * The small Zn2+-DPA ligand appears well suited for
      monitoring therapy. * Treatment effects are detectable just as early with Zn2+
      DPA as with 18F-FDG.

PMID- 24121673
TI  - Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating
      ubiquitination and degradation of YY1.
AB  - About half of patients with diffuse large B-cell lymphoma (DLBCL) do not respond
      to or relapse soon after the standard chemotherapy, indicating a critical need to
      better understand the specific pathways perturbed in DLBCL for developing
      effective therapeutic approaches. Mice deficient in the E3 ubiquitin ligase
      Smurf2 spontaneously develop B-cell lymphomas that resemble human DLBCL with
      molecular features of germinal centre or post-germinal centre B cells. Here we
      show that Smurf2 mediates ubiquitination and degradation of YY1, a key germinal
      centre transcription factor. Smurf2 deficiency enhances YY1-mediated
      transactivation of c-Myc and B-cell proliferation. Furthermore, Smurf2 expression
      is significantly decreased in primary human DLBCL samples, and low levels of
      Smurf2 expression correlate with inferior survival in DLBCL patients. The Smurf2
      YY1-c-Myc regulatory axis represents a novel pathway perturbed in DLBCL that
      suppresses B-cell proliferation and lymphomagenesis, suggesting pharmaceutical
      targeting of Smurf2 as a new therapeutic paradigm for DLBCL. 

PMID- 24121674
TI  - Diverse effects of arsenic on selected enzyme activities in soil-plant-microbe
      interactions.
AB  - Under the influence of pollutants, enzyme activities in plant-microbe-soil
      systems undergo changes of great importance in predicting soil-plant-microbe
      interactions, regulation of metal and nutrient uptake, and, ultimately,
      improvement of soil health and fertility. We evaluated the influence of As on
      soil enzyme activities and the effectiveness of five field crops for As
      phytoextraction. The initial As concentration in soil was 50mg As kg(-1) soil;
      planted clean soil, unplanted polluted soil, and unplanted clean soil served as
      controls. After 10 weeks, the growth of the plants elevated soil dehydrogenase
      activity relative to polluted but unplanted control soils by 2.4- and 2.5-fold
      for sorghum and sunflower (respectively), by 3-fold for ryegrass and sudangrass,
      and by 5.2-fold for spring rape. Soil peroxidase activity increased by 33% with
      ryegrass and rape, while soil phosphatase activity was directly correlated with
      residual As (correlation coefficient R(2)=0.7045). We conclude that soil enzyme
      activities should be taken into account when selecting plants for
      phytoremediation. 

PMID- 24121676
TI  - A comparative computational investigation on the proton and hydride transfer
      mechanisms of monoamine oxidase using model molecules.
AB  - Monoamine oxidase (MAO) enzymes regulate the level of neurotransmitters by
      catalyzing the oxidation of various amine neurotransmitters, such as serotonin,
      dopamine and norepinephrine. Therefore, they are the important targets for drugs
      used in the treatment of depression, Parkinson, Alzeimer and other
      neurodegenerative disorders. Elucidation of MAO-catalyzed amine oxidation will
      provide new insights into the design of more effective drugs. Various amine
      oxidation mechanisms have been proposed for MAO so far, such as single electron
      transfer mechanism, polar nucleophilic mechanism and hydride mechanism. Since
      amine oxidation reaction of MAO takes place between cofactor flavin and the amine
      substrate, we focus on the small model structures mimicking flavin and amine
      substrates so that three model structures were employed. Reactants, transition
      states and products of the polar nucleophilic (proton transfer), the water
      assisted proton transfer and the hydride transfer mechanisms were fully optimized
      employing various semi-empirical, ab initio and new generation density functional
      theory (DFT) methods. Activation energy barriers related to these mechanisms
      revealed that hydride transfer mechanism is more feasible. 

PMID- 24121675
TI  - A systems chemical biology study of malate synthase and isocitrate lyase
      inhibition in Mycobacterium tuberculosis during active and NRP growth.
AB  - The ability of Mycobacterium tuberculosis (Mtb) to survive in low oxygen
      environments enables the bacterium to persist in a latent state within host
      tissues. In vitro studies of Mtb growth have identified changes in isocitrate
      lyase (ICL) and malate synthase (MS) that enable bacterial persistence under low
      oxygen and other environmentally limiting conditions. Systems chemical biology
      (SCB) enables us to evaluate the effects of small molecule inhibitors not only on
      the reaction catalyzed by malate synthase and isocitrate lyase, but the effect on
      the complete tricarboxylic acid cycle (TCA) by taking into account complex
      network relationships within that system. To study the kinetic consequences of
      inhibition on persistent bacilli, we implement a systems-chemical biology (SCB)
      platform and perform a chemistry-centric analysis of key metabolic pathways
      believed to impact Mtb latency. We explore consequences of disrupting the
      function of malate synthase (MS) and isocitrate lyase (ICL) during aerobic and
      hypoxic non-replicating persistence (NRP) growth by using the SCB method to
      identify small molecules that inhibit the function of MS and ICL, and simulating
      the metabolic consequence of the disruption. Results indicate variations in
      target and non-target reaction steps, clear differences in the normal and low
      oxygen models, as well as dosage dependent response. Simulation results from
      singular and combined enzyme inhibition strategies suggest ICL may be the more
      effective target for chemotherapeutic treatment against Mtb growing in a
      microenvironment where oxygen is slowly depleted, which may favor persistence. 

PMID- 24121677
TI  - Dioxygen and superoxide stability of metallopeptide based mimics of nickel
      containing superoxide dismutase: the influence of amine/amidate vs. bis-amidate
      ligation.
AB  - Nickel containing superoxide dismutase (NiSOD) is a metalloenzyme that catalyzes
      the disproportionation of O2(-). In its reduced state, the Ni(II) ion is
      coordinated by two cis-cysteinates, an amine nitrogen and an amidate nitrogen
      atom. It thus bears a resemblance to the distal bis-cysteinate bis-amidate
      ligated nickel center of acetyl coenzyme A synthase. Using metallopeptide based
      NiSOD mimics derived from the first 12 residues of the NiSOD sequence we
      demonstrate that altering the primary coordination sphere from a bis-thiolate
      amine/amidate motif to a bis-thiolate bis-amidate motif changes the O2 and ROS
      stability of the metallopeptide. Using FT-IR, ESI-MS and S K-edge XAS we show
      that the bis-amidate bis-thiolate ligated metallopeptide {Ni(II)(SOD(m1)-Ac)}
      (SOD(m1)-Ac=AcHN-HCDLPCGVYSPA-COOH) undergoes oxidation at one thiolate ligand in
      the presence of O2, converting it into a coordinated sulfinate. Upon exposure of
      {Ni(II)(SOD(m1)-Ac)} to O2(-) the metallopeptide undergoes extensive sulfur
      oxidation. This can be contrasted with the unacylated metallopeptide
      {Ni(II)(SOD(m1))} which does not undergo sulfur based oxidation under these
      conditions. The biological implications of these findings are discussed. 

PMID- 24121678
TI  - Protective role of PARK2/Parkin in sepsis-induced cardiac contractile and
      mitochondrial dysfunction.
AB  - Mitochondrial quality control plays a vital role in the maintenance of optimal
      mitochondrial function. However, its roles and regulation remain ill-defined in
      cardiac pathophysiology. Here, we tested the hypothesis that PARK2/Parkin, an E3
      ligase recently described as being involved in the regulation of cardiac
      mitophagy, is important for (1) the maintenance of normal cardiac mitochondrial
      function; and (2) adequate recovery from sepsis, a condition known to induce
      reversible mitochondrial injury through poorly understood mechanisms.
      Investigations of mitochondrial and cardiac function were thus performed in wild
      type and Park2-deficient mice at baseline and at 2 different times following
      administration of a sublethal dose of E. coli lipopolysaccharide (LPS). LPS
      injection induced cardiac and mitochondrial dysfunctions that were followed by
      complete recovery in wild-type mice. Recovery was associated with morphological
      and biochemical evidence of mitophagy, suggesting that this process is implicated
      in cardiac recovery from sepsis. Under baseline conditions, multiple cardiac
      mitochondrial dysfunctions were observed in Park2-deficient mice. These mild
      dysfunctions did not result in a visibly distinct cardiac phenotype. Importantly,
      Park2-deficient mice exhibited impaired recovery of cardiac contractility and
      constant degradation of mitochondrial metabolic functions. Interestingly,
      autophagic clearance of damaged mitochondria was still possible in the absence of
      PARK2 likely through compensatory mechanisms implicating PARK2-independent
      mitophagy and upregulation of macroautophagy. Together, these results thus
      provide evidence that in vivo, mitochondrial autophagy is activated during
      sepsis, and that compensation for a lack of PARK2 is only partial and/or that
      PARK2 exerts additional protective roles in mitochondria. 

PMID- 24121679
TI  - Analysis of fatty acid content and composition in microalgae.
AB  - A method to determine the content and composition of total fatty acids present in
      microalgae is described. Fatty acids are a major constituent of microalgal
      biomass. These fatty acids can be present in different acyl-lipid classes.
      Especially the fatty acids present in triacylglycerol (TAG) are of commercial
      interest, because they can be used for production of transportation fuels, bulk
      chemicals, nutraceuticals (omega-3 fatty acids), and food commodities. To develop
      commercial applications, reliable analytical methods for quantification of fatty
      acid content and composition are needed. Microalgae are single cells surrounded
      by a rigid cell wall. A fatty acid analysis method should provide sufficient cell
      disruption to liberate all acyl lipids and the extraction procedure used should
      be able to extract all acyl lipid classes. With the method presented here all
      fatty acids present in microalgae can be accurately and reproducibly identified
      and quantified using small amounts of sample (5 mg) independent of their chain
      length, degree of unsaturation, or the lipid class they are part of. This method
      does not provide information about the relative abundance of different lipid
      classes, but can be extended to separate lipid classes from each other. The
      method is based on a sequence of mechanical cell disruption, solvent based lipid
      extraction, transesterification of fatty acids to fatty acid methyl esters
      (FAMEs), and quantification and identification of FAMEs using gas chromatography
      (GC-FID). A TAG internal standard (tripentadecanoin) is added prior to the
      analytical procedure to correct for losses during extraction and incomplete
      transesterification. 

PMID- 24121680
TI  - Formation and reactivity of an (alkene)peroxoiridium(III) intermediate supported
      by an amidinato ligand.
AB  - An Ir(I) complex of an acetamidinato ligand was synthesized by reaction of N,N'
      diphenylacetamidine, PhN[double bond, length as m-dash]C(Me)NHPh, with either
      MeLi and [{Ir(cod)}2(MU-Cl)2] or [{Ir(cod)}2(MU-OMe)2] and was characterized by X
      ray crystallography as a mononuclear complex, [Ir{PhNC(Me)NPh}(cod)] (1; where
      cod = 1,5-cyclooctadiene). Reaction of 1 with CO afforded a dinuclear carbonyl
      complex, [{Ir(CO)2}2{MU-PhNC(Me)NPh-kappaN:kappaN'}2] (2), as indicated by EI
      mass spectrometry and solution- and solid-state IR spectroscopy [nuCO (n-pentane)
      = 2067, 2034 and 1992 cm(-1)]. Activation of O2 by 1 in solution at 20  degrees C
      was irreversible and produced an (alkene)peroxoiridium(iii) intermediate,
      [Ir{PhNC(Me)NPh}(cod)(O2)] (3), which was characterized by one- and two
      dimensional NMR techniques and IR spectroscopy (for 3, nuOO = 860 cm(-1); for 3
      (18)O2, nuOO = 807 cm(-1)). Complex 3 oxidized PPh3 to OPPh3, and its decay in
      the absence of added substrates followed by reaction with cod yielded 4
      cycloocten-1-one and a minor amount of 1. In comparison with the results for the
      previously reported guanidinato complex [Ir{PhNC(NMe2)NPh}(cod)(O2)] (4), the
      formation of 3 and its reaction with PPh3 are significantly faster, indicating
      considerable ligand effects in these reactions. 

PMID- 24121681
TI  - Conformational and thermodynamic hallmarks of DNA operator site specificity in
      the copper sensitive operon repressor from Streptomyces lividans.
AB  - Metal ion homeostasis in bacteria relies on metalloregulatory proteins to
      upregulate metal resistance genes and enable the organism to preclude metal
      toxicity. The copper sensitive operon repressor (CsoR) family is widely
      distributed in bacteria and controls the expression of copper efflux systems.
      CsoR operator sites consist of G-tract containing pseudopalindromes of which the
      mechanism of operator binding is poorly understood. Here, we use a structurally
      characterized CsoR from Streptomyces lividans (CsoR(Sl)) together with three
      specific operator targets to reveal the salient features pertaining to the
      mechanism of DNA binding. We reveal that CsoR(Sl) binds to its operator site
      through a 2-fold axis of symmetry centred on a conserved 5'-TAC/GTA-3' inverted
      repeat. Operator recognition is stringently dependent not only on electropositive
      residues but also on a conserved polar glutamine residue. Thermodynamic and
      circular dichroic signatures of the CsoR(Sl)-DNA interaction suggest selectivity
      towards the A-DNA-like topology of the G-tracts at the operator site. Such
      properties are enhanced on protein binding thus enabling the symmetrical binding
      of two CsoR(Sl) tetramers. Finally, differential binding modes may exist in
      operator sites having more than one 5'-TAC/GTA-3' inverted repeat with
      implications in vivo for a mechanism of modular control. 

PMID- 24121682
TI  - New scoring system to identify RNA G-quadruplex folding.
AB  - G-quadruplexes (G4s) are non-canonical structures involved in many important
      cellular processes. To date, the prediction of potential G-quadruplex structures
      (PG4s) has been based almost exclusively on the sequence of interest agreeing
      with the algorithm Gx-N-1-7-Gx-N1-7-Gx-N1-7-Gx (where x >= 3 and N = A, U, G or
      C). However, many sequences agreeing with this algorithm do not form G4s and are
      considered false-positive predictions. Here we show the RNA PG4 candidate in the
      3'-untranslated region (UTR) of the TTYH1 gene to be one such false positive.
      Specifically, G4 folding was observed to be inhibited by the presence of multiple
      cytosine tracks, located in the candidate's genomic context, that adopted a
      Watson-Crick base-paired structure. Clearly, the neighbouring sequences of a PG4
      may influence its folding. The secondary structure of 12 PG4 motifs along with
      either 15 or 50 nucleotides of their upstream and downstream genomic contexts
      were evaluated by in-line probing. Data permitted the development of a scoring
      system for the prediction of PG4s taking into account the effect of the
      neighbouring sequences. The accuracy of this scoring system was assessed by
      probing 14 other novel PG4 candidates retrieved in human 5'-UTRs. This new
      scoring system can be used, in combination with the standard algorithm, to better
      predict the folding of RNA G4s. 

PMID- 24121683
TI  - Higher order structural effects stabilizing the reverse Watson-Crick Guanine
      Cytosine base pair in functional RNAs.
AB  - The G:C reverse Watson-Crick (W:W trans) base pair, also known as Levitt base
      pair in the context of tRNAs, is a structurally and functionally important base
      pair that contributes to tertiary interactions joining distant domains in
      functional RNA molecules and also participates in metabolite binding in
      riboswitches. We previously indicated that the isolated G:C W:W trans base pair
      is a rather unstable geometry, and that dicationic metal binding to the Guanine
      base or posttranscriptional modification of the Guanine can increase its
      stability. Herein, we extend our survey and report on other H-bonding
      interactions that can increase the stability of this base pair. To this aim, we
      performed a bioinformatics search of the PDB to locate all the occurencies of G:C
      trans base pairs. Interestingly, 66% of the G:C trans base pairs in the PDB are
      engaged in additional H-bonding interactions with other bases, the RNA backbone
      or structured water molecules. High level quantum mechanical calculations on a
      data set of representative crystal structures were performed to shed light on the
      structural stability and energetics of the various crystallographic motifs. This
      analysis was extended to the binding of the preQ1 metabolite to a preQ1-II
      riboswitch. 

PMID- 24121684
TI  - Staphylococcus epidermidis Csm1 is a 3'-5' exonuclease.
AB  - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) offer an
      adaptive immune system that protects bacteria and archaea from nucleic acid
      invaders through an RNA-mediated nucleic acid cleavage mechanism. Our knowledge
      of nucleic acid cleavage mechanisms is limited to three examples of widely
      different ribonucleoprotein particles that target either DNA or RNA.
      Staphylococcus epidermidis belongs to the Type III-A CRISPR system and has been
      shown to interfere with invading DNA in vivo. The Type III-A CRISPR system is
      characterized by the presence of Csm1, a member of Cas10 family of proteins, that
      has a permuted histidine-aspartate domain and a nucleotidyl cyclase-like domain,
      both of which contain sequence features characteristic of nucleases. In this
      work, we show in vitro that a recombinant S. epidermidis Csm1 cleaves single
      stranded DNA and RNA exonucleolytically in the 3'-5' direction. We further showed
      that both cleavage activities are divalent-metal-dependent and reside in the GGDD
      motif of the cyclase-like domain. Our data suggest that Csm1 may work in the
      context of an effector complex to degrade invading DNA and participate in CRISPR
      RNA maturation. 

PMID- 24121685
TI  - Novel fluorescent genome editing reporters for monitoring DNA repair pathway
      utilization at endonuclease-induced breaks.
AB  - The creation of a DNA break at a specific locus by a designer endonuclease can be
      harnessed to edit a genome. However, DNA breaks may engage one of several
      competing repair pathways that lead to distinct types of genomic alterations.
      Therefore, understanding the contribution of different repair pathways following
      the introduction of a targeted DNA break is essential to further advance the
      safety and efficiency of nuclease-induced genome modification. To gain insight
      into the role of different DNA repair pathways in resolving nuclease-induced DNA
      breaks into genome editing outcomes, we previously developed a fluorescent-based
      reporter system, designated the Traffic Light Reporter, which provides a readout
      of gene targeting and gene disruption downstream of a targeted DNA double-strand
      break. Here we describe two related but novel reporters that extend this
      technology: one that allows monitoring of the transcriptional activity at the
      reporter locus, and thus can be applied to interrogate break resolution at active
      and repressed loci; and a second that reads out single-strand annealing in
      addition to gene targeting and gene disruption. Application of these reporters to
      assess repair pathway usage in several common gene editing contexts confirms the
      importance that chromatin status and initiation of end resection have on the
      resolution of nuclease-induced breaks. 

PMID- 24121686
TI  - The intrinsically disordered distal face of nucleoplasmin recognizes distinct
      oligomerization states of histones.
AB  - The role of Nucleoplasmin (NP) as a H2A-H2B histone chaperone has been
      extensively characterized. To understand its putative interaction with other
      histone ligands, we have characterized its ability to bind H3-H4 and histone
      octamers. We find that the chaperone forms distinct complexes with histones,
      which differ in the number of molecules that build the assembly and in their
      spatial distribution. When complexed with H3-H4 tetramers or histone octamers,
      two NP pentamers form an ellipsoidal particle with the histones located at the
      center of the assembly, in stark contrast with the NP/H2A-H2B complex that
      contains up to five histone dimers bound to one chaperone pentamer. This
      particular assembly relies on the ability of H3-H4 to form tetramers either in
      solution or as part of the octamer, and it is not observed when a variant of H3
      (H3C110E), unable to form stable tetramers, is used instead of the wild-type
      protein. Our data also suggest that the distal face of the chaperone is involved
      in the interaction with distinct types of histones, as supported by electron
      microscopy analysis of the different NP/histone complexes. The use of the same
      structural region to accommodate all type of histones could favor histone
      exchange and nucleosome dynamics. 

PMID- 24121687
TI  - Quantitative influence of macromolecular crowding on gene regulation kinetics.
AB  - We introduce macromolecular crowding quantitatively into the model for kinetics
      of gene regulation in Escherichia coli. We analyse and compute the specific-site
      searching time for 180 known transcription factors (TFs) regulating 1300 operons.
      The time is between 160 s (e.g. for SoxS Mw = 12.91 kDa) and 1550 s (e.g. for
      PepA6 of Mw = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are
      between for large proteins up to for small monomers or dimers. Three-dimensional
      diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D
      sliding coefficients, nevertheless the sliding enhances the binding rates of TF
      to specific sites by 1-2 orders of magnitude. The latter effect is due to
      ubiquitous non-specific binding. We compare the model to experimental data for
      LacI repressor and find that non-specific binding of the protein to DNA is
      activation- and not diffusion-limited. We show that the target location rate by
      LacI repressor is optimized with respect to microscopic rate constant for
      association to non-specific sites on DNA. We analyse the effect of
      oligomerization of TFs and DNA looping effects on searching kinetics. We show
      that optimal searching strategy depends on TF abundance. 

PMID- 24121689
TI  - Histopathological findings of endometrial specimens in abnormal uterine bleeding.
AB  - PURPOSE: The aim of this study was to assess the frequency of different
      histopathological findings obtained from dilatation and curettage (D&C) specimens
      in patients with abnormal uterine bleeding (AUB). METHODS: In a retrospective
      review of 591 specimens, the included subjects were all women with AUB who
      underwent D&C between 2002 and 2006 in Be'sat Hospital, Tehran, Iran. The
      pathological diagnoses were analyzed in four groups from normal to malignant
      endometrium. The pathological groups were evaluated for patients' characteristics
      including demographic data and medical history. RESULTS: The majority of patients
      (61.6%) were in the 41-50 year age group. Totally, 81.4% of patients had normal
      pathology. The disordered proliferative endometrium/polyps, hyperplasia, and
      malignant pathology were found in 15.4, 2.5, and 0.7% of specimens, respectively.
      The abnormal pathologies were seen more among patients with postmenopausal
      status, nulli-/primigravid women, and those with hypertension, diabetes,
      hypothyroidism, and polycystic ovary syndrome. CONCLUSIONS: The proliferative
      endometrium and secretory endometrium were the most common histopathological
      observations in AUB patients in our region, and except normal endometrium,
      disordered proliferative endometrium was the most common cause of AUB.

PMID- 24121688
TI  - CTCF binding site sequence differences are associated with unique regulatory and
      functional trends during embryonic stem cell differentiation.
AB  - CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding
      protein with thousands of binding sites genome-wide. Our previous work suggested
      that differences in CTCF's binding site sequence may affect the regulation of
      CTCF recruitment and its function. To investigate this possibility, we
      characterized changes in genome-wide CTCF binding and gene expression during
      differentiation of mouse embryonic stem cells. After separating CTCF sites into
      three classes (LowOc, MedOc and HighOc) based on similarity to the consensus
      motif, we found that developmentally regulated CTCF binding occurs preferentially
      at LowOc sites, which have lower similarity to the consensus. By measuring the
      affinity of CTCF for selected sites, we show that sites lost during
      differentiation are enriched in motifs associated with weaker CTCF binding in
      vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding
      site is associated with regulated binding in the LowOc class and can predictably
      reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF
      binding with changes in gene expression during differentiation, we show that
      LowOc and HighOc sites are associated with distinct regulatory functions. Our
      results suggest that the regulatory control of CTCF is dependent in part on
      specific motifs within its binding site. 

PMID- 24121690
TI  - Letrozole ovulation induction: an effective option in endometrial preparation for
      frozen-thawed embryo transfer.
AB  - PURPOSE: To evaluate the clinical efficacy of letrozole on ovulation induction
      and hormone replacement therapy (HRT) during endometrial preparation for frozen
      thawed embryo transfer (FET). METHODS: We analyzed totally 1,230 cycles of
      patients that underwent FET from October 2010 to September 2012. Seven hundred
      and thirteen cycles of patients with ovulation disorders that underwent FET were
      randomly assigned to two groups by case control study. 359 cycles received
      letrozole ovulation induction and 354 cycles received HRT during endometrial
      preparation for FET, respectively. In the corresponding period, 517 cycles of
      patients with normal ovulation in the natural cycle group for FET endometrial
      preparation served as controls. Reproduction-related clinical outcomes of
      patients in the three groups were compared. RESULTS: The embryo implantation rate
      of patients in letrozole group (30.4 %) was significantly higher than the HRT
      group (22.8 %, P < 0.05). The clinical pregnancy rate of patients in the
      letrozole group (53.2 %) was significantly higher than the HRT group (44.4 %, P <
      0.05), while no significant difference was observed between the letrozole and
      natural cycle groups (51.3 %, P > 0.05). Estradiol levels on the day of human
      chorionic gonadotropin administration in the letrozole group were significantly
      lower than those in the natural cycle group (280.32 +/- 125.39 pg/ml and 351.06
      +/- 123.03 pg/ml, respectively; P < 0.05). The live birth rate of patients in
      letrozole group (44.6 %) was significantly higher than the HRT group (32.5 %, P <
      0.05), while abortion rate (12.0 %) was significantly lower than the HRT group
      (21.0 %, P < 0.05). There were no significant differences in number of mature
      follicles, endometrial thickness, duration of follicle growth between the
      letrozole and the natural cycle groups, and there were no significant differences
      in twin birth rate and ectopic pregnancy rate among the three groups (all P
      values >0.05). CONCLUSIONS: Ovulation induction with letrozole during endometrial
      preparation for FET has a higher rate of pregnancy success and a lower abortion
      rate than HRT. Letrozole treatment exhibits clinical progression and outcomes
      similar to those patients undergoing a natural cycle or normal ovulation cycle.
      Therefore, letrozole treatment may be an effective option in endometrial
      preparation for FET in patients with ovulation disorders or irregular
      menstruation.

PMID- 24121691
TI  - Socioeconomic status and depression during and after pregnancy in the Franconian
      Maternal Health Evaluation Studies (FRAMES).
AB  - PURPOSE: Depression during and after pregnancy can have a negative impact on
      women's quality of life and on the development of the newborn child.
      Interventions have been shown to have a positive influence on both mothers and
      children. Predictive factors for depressive symptoms might possibly be able to
      identify groups that are at high risk. The aim of this study was to investigate
      the value of socioeconomic factors in predicting depressive symptoms during and
      after pregnancy. METHODS: Depressiveness was measured using the German version of
      the 10-item Edinburgh Postnatal Depression Scale (EPDS) at three time-points, in
      a prospective cohort study (n = 1,100). Visit 1 (Q1) was at study entry in the
      third trimester of the pregnancy, visit 2 (Q2) was shortly after birth, and visit
      3 (Q3) was 6-8 months after birth. Depression scores were associated with
      socioeconomic factors and time in linear mixed models. RESULTS: Parity status,
      education status, monthly income, residential property status, and partnership
      status, as well as interactions between them, were found to be predictive factors
      for EPDS scores. The strongest factor influencing depressive symptoms was
      partnership status. Women who did not have an intact partnership had EPDS scores
      that were on average four points higher than in women with a partner at all three
      study visits (P < 0.000001). CONCLUSIONS: Socioeconomic factors define subgroups
      that have different depression scores during and after pregnancy. Partnership
      status appears to be one of the most important influencing factors and could be
      useful for identifying women who should be offered an intervention to prevent
      possible negative effects on the mother or child.

PMID- 24121692
TI  - The role of gel application in decreasing pain during speculum examination and
      its effects on papanicolaou smear results.
AB  - PURPOSE: This study aimed to investigate the effects of water-based gel
      application in reducing pain or discomfort associated with speculum examination,
      and compared the presence of unsatisfactory Papanicolaou smear results between
      gel-applied and control groups. METHODS: In this prospective randomized
      controlled study, a total of 1,580 patients were analyzed. The subjects were
      randomized to a gel group and a control group. For the collection of the smear
      sample, water-based gel was used in the gel group and dry speculum was used in
      the control group. All patients were asked to score their pain on a numeric pain
      scale at two time points during the procedure (insertion and opening phase of
      speculum). Cytopathologists who analyzed the smear cytology were blinded to the
      study. Pain intensity during speculum examination, as well as unsatisfactory
      smear results, were analyzed between the groups. RESULTS: The pain scores
      obtained at two different time points of speculum application were significantly
      lower in the gel group compared to the control group both in premenopausal and
      postmenopausal women (p < 0.001). The ratios of unsatisfactory cytopathologic
      examination results were 1.13 and 1.39% for the gel-applied and control groups,
      which were not significantly different. CONCLUSION: Lubrication of the outer
      superior and inferior blade of the plastic vaginal speculum with a small amount
      of a water-soluble lubricant gel decreases the pain associated with insertion and
      opening of the vaginal speculum in both premenopausal and postmenopausal women
      without affecting the quality of the cytology results during the collection of
      Papanicolaou test specimens.

PMID- 24121693
TI  - Mechanism of pain generation for endometriosis-associated pelvic  pain.
AB  - PURPOSE: Endometriosis-associated pelvic pain appears due to persistent
      nociceptive stimulation, but the precise mechanisms remain poorly understood.
      METHODS: A search was conducted to screen and select articles from PubMed. MAIN
      RESULTS: Neurotrophins (NTs), a family of neuronal growth factors, are
      overexpressed in endometriosis and encompass NGF, BDNF and NT-3 and NT-4/5. NT
      receptors, TrkA and p75NTR, and NT receptor-interacting proteins, MAGE and NDN,
      were also expressed. NTs and their receptors play a role in the development and
      maintenance of neural tissues in non-neuronal cell types such as endometriosis.
      Nerve fibers contain unmyelinated sensory C, myelinated sensory Adelta and
      adrenergic nerve fibers that innervate abnormal cell growths. An increased
      release of proinflammatory cytokines from endometriotic lesions is responsible
      for the excessive sensory innervation and development of chronic pelvic pain.
      CONCLUSIONS: The preponderance of the inflammatory milieu and subsequent
      hyperinnervation might be involved in the pathophysiology of pain generation in
      women with endometriosis.

PMID- 24121694
TI  - Tea and the culture of nursing.

PMID- 24121695
TI  - Innovation: risky business.

PMID- 24121696
TI  - Understanding nurses' experiences of providing end-of-life care in the US
      hospital setting.
AB  - Hermeneutic phenomenological methods were used to explore nurses' perspectives on
      the phenomenon of end-of-life care within the hospital setting. Three main themes
      described participants' experiences: "Confronting Challenges," "Coming to
      Understand End-of-Life Care," and "Transforming the Understanding of End-of-Life
      Care into Nursing Practice." Recommendations for education, practice, and
      research were derived. 

PMID- 24121697
TI  - Factors affecting shared decision making at end of life in Korean adults.
AB  - The purpose of this study was to explore the factors affecting shared decision
      making among Korean adults. Attitudes toward advance directives and withdrawal of
      life-sustaining treatment explained 45.0% of shared decision making, suggesting
      that these 2 factors influence shared decision making in end-of-life care. 

PMID- 24121698
TI  - Lessons learned from a study of a complementary therapy for self-managing
      hypertension and stress in women.
AB  - This report evaluates a Hawaiian-based, self-management intervention for reducing
      blood pressure (BP) and stress in women. It highlights lessons learned when using
      nonpharmacologic, complementary and alternative medicine (CAM) therapies.
      Specific participant characteristics and preferences should be considered for
      optimizing health outcomes in CAM research in nursing practice. 

PMID- 24121699
TI  - Disciplined care for disciplined patients: experience of hospitalized blind
      patients.
AB  - Blindness is a permanent condition that alters daily life of blind people.
      Interpretive phenomenology was used to understand lived experiences of the
      hospitalized blind people. "Disciplined care for disciplined patients" was one of
      the themes that emerged from the data. Provision of disciplined care can help
      health care professionals provide a holistic and comprehensive competent care for
      blind patients. 

PMID- 24121700
TI  - Evaluation of "Steps to Surgical Success" (STEPS): a holistic perioperative
      medicine program to manage pain and anxiety related to surgery.
AB  - This empirical study found that a holistic perioperative program significantly
      reduced patient pain and anxiety about surgery. Modalities included guided
      imagery, eye pillow, aromatherapy, and a written personal healing plan. Nurses
      are in a prime position to deliver these interventions, given their frequent
      direct contact with patients. 

PMID- 24121701
TI  - Examination of pain experiences of cancer patients in western Turkey: a
      phenomenological study.
AB  - This study aims to explore the individual experience of living with cancer pain.
      This qualitative study was performed by using a phenomenological research design.
      In-depth and open interviews with participants were conducted to collect the data
      and a qualitative Colaizzi method of analysis was performed. Following the
      analysis of the data, the expressions made by the cancer patients during the
      interviews were grouped under 5 themes. Consistent with the questionnaire format,
      5 themes and 19 subthemes of responses were determined describing the pain of the
      cancer patients. The results of our study have demonstrated that cancer patients
      go through negative physical, psychological, and social experiences due to the
      pain they suffered. 

PMID- 24121702
TI  - Generalized anxiety disorder (GAD): efficacy of standardized Matricaria recutita
      (German chamomile) extract in the treatment of generalized anxiety disorder.

PMID- 24121703
TI  - Reduction of CO2 to low carbon alcohols on CuO FCs/Fe2O3 NTs catalyst with
      photoelectric dual catalytic interfaces.
AB  - In this paper, the CuO FCs/Fe2O3 NTs catalyst was obtained after Fe2O3 nanotubes
      (Fe2O3 NTs) were decorated with CuO flower clusters (CuO FCs) by the pulse
      electrochemical deposition method. The in situ vertically aligned Fe2O3 NTs were
      prepared on the ferrous substrate by a potentiostatic anodization method. The SEM
      result showed the volcano-like Fe2O3 NTs were arranged in order and the CuO FCs
      constituted of flaky CuO distributed on the Fe2O3 NTs surface uniformly. After
      CuO FCs were loaded on Fe2O3 NTs, the absorption of visible light was enhanced
      noticeably, and its band gap narrowed to 1.78 eV from 2.03 eV. The conduction
      band and valence band locating at -0.73 eV and 1.05 eV, respectively were further
      obtained. In the PEC reduction of CO2 process, methanol and ethanol were two
      major products identified by chromatography. Their contents reached 1.00 mmol L(
      1) cm(-2) and 107.38 MUmol L(-1) cm(-2) after 6 h, respectively. This high
      efficiency catalyst with photoelectric dual catalytic interfaces has a great
      guidance and reference significance for CO2 reduction to liquid carbon fuels. 

PMID- 24121704
TI  - Tools and techniques to measure mitophagy using fluorescence microscopy.
AB  - Mitophagy is a specialized form of autophagy that removes damaged mitochondria,
      thereby maintaining efficient cellular metabolism and reducing cellular stress
      caused by aberrant oxidative bursts. Deficits in mitophagy underlie several
      diseases, and a substantial body of research has elucidated key steps in the
      pathways that lead to and execute autophagic clearance of mitochondria. Many of
      these studies employ fluorescence microscopy to visualize mitochondrial
      morphology, mass, and functional state. Studies in this area also examine
      colocalization/recruitment of accessory factors, components of the autophagic
      machinery and signaling molecules to mitochondria. In this review, we provide a
      brief summary of the current understanding about the processes involved in
      mitophagy followed by a discussion of probes commonly employed and important
      considerations of the methodologies to study and analyze mitophagy using
      fluorescence microscopy. Representative data, where appropriate, are provided to
      highlight the use of key probes to monitor mitophagy. The review will conclude
      with a consideration of new possibilities for mitophagy research and a discussion
      of recently developed technologies for this emerging area of cell biology. 

PMID- 24121705
TI  - Dynamin 1-like-dependent mitochondrial fission initiates overactive mitophagy in
      the hepatotoxicity of cadmium.
AB  - How cadmium (Cd) induces mitochondrial loss in the context of its hepatotoxic
      effects remains enigmatic. The purpose of the study was to investigate whether
      mitophagy contributes to mitochondrial loss in cadmium-induced hepatotoxicity and
      to determine the potential mechanism. In normal human liver L02 cells, we
      observed that Cd treatment led to a significant increase in LC3-II formation, the
      number of GFP-LC3 puncta and lysosomal colocalization with mitochondria. These
      results were associated with mitochondrial loss and bioenergetic deficit.
      Additionally, the abrogation of excessive mitophagy by ATG5 siRNA treatment
      efficiently suppressed the mitochondrial loss and cytotoxicity of Cd. Before
      overactivating mitophagy, Cd induced excessive mitochondrial fragmentation as a
      result of increasing dynamin 1-like (DNM1L) expression and enhancing the DNM1L
      mitochondrial translocation. Moreover, reversing the excessive mitochondrial
      fragmentation via the administration of DNM1L siRNA significantly inhibited the
      observed overactivation of mitophagy in Cd-induced hepatotoxicity. Notably, the
      selective DNM1L inhibitor Mdivi-1 blocked abnormal mitophagy and subsequently
      ameliorated Cd-induced hepatotoxicity in vivo. Together, our data indicated that
      Cd induces mitochondrial loss via the overactivation of mitophagy following DNM1L
      dependent mitochondrial fragmentation. The balanced activity of DNM1L and
      mitophagy signaling may be a potential therapeutic approach to treat Cd-induced
      hepatotoxicity. 

PMID- 24121706
TI  - PINK1 is degraded through the N-end rule pathway.
AB  - PINK1, a mitochondrial serine/threonine kinase, is the product of a gene mutated
      in an autosomal recessive form of Parkinson disease. PINK1 is constitutively
      degraded by an unknown mechanism and stabilized selectively on damaged
      mitochondria where it can recruit the E3 ligase PARK2/PARKIN to induce mitophagy.
      Here, we show that, under steady-state conditions, endogenous PINK1 is
      constitutively and rapidly degraded by E3 ubiquitin ligases UBR1, UBR2 and UBR4
      through the N-end rule pathway. Following precursor import into mitochondria,
      PINK1 is cleaved in the transmembrane segment by a mitochondrial intramembrane
      protease PARL generating an N-terminal destabilizing amino acid and then
      retrotranslocates from mitochondria to the cytosol for N-end recognition and
      proteasomal degradation. Thus, sequential actions of mitochondrial import, PARL
      processing, retrotranslocation and recognition by N-end rule E3 enzymes for the
      ubiquitin proteosomal degradation defines the rapid PINK1 turnover. PINK1 steady
      state elimination by the N-end rule identifies a novel organelle to cytoplasm
      turnover pathway that yields a mechanism to flag damaged mitochondria for
      autophagic elimination. 

PMID- 24121707
TI  - Perturbed mitochondrial Ca2+ signals as causes or consequences of mitophagy
      induction.
AB  - Mitophagy is an essential process that maintains mitochondrial quality and
      number, thus limiting cellular degeneration. Along with apoptosis, mitophagy
      participates in cellular fate decisions by eliminating damaged mitochondria. A
      variety of mitochondrial parameters, such as structure, membrane potential, and
      reactive oxygen species, are key determinants in triggering the mitophagic
      machinery. These parameters are also important regulators of the mitochondrial
      capacity for calcium (Ca (2+)) uptake. Rapid Ca (2+) accumulation in the
      mitochondrial matrix allows for prompt stimulation of the organelle. This process
      requires a close morphofunctional coupling between mitochondria and the main
      intracellular Ca (2+) stores. In mitophagy, the role of Ca (2+) remains obscure.
      What role does mitochondrial Ca (2+) play in metabolic sensing or in
      mitochondrial remodeling? Is endoplasmic reticulum (ER)-Ca (2+) crosstalk
      involved? These are some of the questions that we address in this review. 

PMID- 24121708
TI  - Ca2+ in quality control: an unresolved riddle critical to autophagy and
      mitophagy.
AB  - Calcium (Ca (2+)) has long been known as a ubiquitous intracellular second
      messenger, exploited by cells to control processes as diverse as development,
      proliferation, learning, muscle contraction and secretion. The spatial and
      temporal patterns of these Ca (2+)-associated signals, as well as their
      amplitude, is precisely controlled to create gradients of the ion, varying
      considerably depending on cell type and function. Tuning of intracellular Ca (2+)
      is achieved in part by the buffering role of mitochondria, whose unperturbed
      function is essential for maintaining cellular energy balance. Quality of
      mitochondria is ensured by the process of targeted autophagy or mitophagy, which
      depends on a molecular cascade driving the catabolic process of autophagy toward
      damaged or deficient organelles for elimination via the lysosomal pathway.
      Nonspecific and targeted autophagy are highly regulated processes fundamental to
      cell growth and tissue homeostasis, allowing resources to be reallocated in
      nutrient-deprived cells as well as being instrumental in the repair of damaged
      organelles or the elimination of those in excess. Given the role of Ca (2+)
      signaling in many fundamental cellular processes requiring precise regulation,
      the involvement of Ca (2+) in autophagy is still somewhat ill-defined, and only
      in the past few years has evidence emerged linking the two. This mini-review aims
      to summarize recent work implicating Ca (2+) as an important regulator of
      autophagy, outlining a role for Ca (2+) that may be even more critical in the
      regulation of targeted mitochondrial autophagy. 

PMID- 24121709
TI  - Autophagy researchers.

PMID- 24121710
TI  - The relation between mirror self-image reactions and imitation in 14- and 18
      month-old infants.
AB  - Previous research suggests that sensitivity to aspects of the self and others
      develop in tandem. We tested 14- and 18-month-olds' imitative abilities and
      mirror self-image reactions (i.e., testing behavior and passing the mark test).
      Results showed that 14-month-olds' imitation was closely related to the
      occurrence of testing behavior in front of the mirror, where they checked whether
      they could control the movements of the mirror image. Eighteen-month-olds,
      however, no longer showed this relation. Furthermore, in 18-month-olds, we found
      a high association between imitation and passing the mark test. These
      correlations suggest that infants' mirror self-image reactions and imitation
      share the ability to detect and produce visual-motor contingencies. 

PMID- 24121711
TI  - Contingent auditory feedback of arm movement facilitates reaching behavior in
      infancy.
AB  - The purpose of this study was to investigate the influence of contingent auditory
      feedback on the development of infant reaching. Eleven full-term infants were
      observed biweekly from the age of 10 weeks to 16 weeks, and their arm kinematics
      were recorded. Auditory feedback that was contingent on arm kinematics was
      provided in the form of: (a) the mother's voice; and (b) musical tones. Results
      showed that providing auditory feedback (mother's voice or musical tones): (i)
      increased the amplitude of exploratory arm movements before the onset of
      reaching; and (ii) increased the number of reaches at the onset of reaching.
      These results show that infants are able to use contingent auditory feedback to
      explore the relevant possibilities for action that are subsequently shaped into
      goal-directed movements. 

PMID- 24121712
TI  - Diagnostic accuracy of digital breast tomosynthesis versus digital mammography
      for benign and malignant lesions in breasts: a meta-analysis.
AB  - OBJECTIVE: To evaluate the diagnostic performance of digital breast tomosynthesis
      (DBT) and digital mammography (DM) for benign and malignant lesions in breasts.
      METHODS: Document retrieval was conducted on PubMed, EMBASE, the Cochrane
      Library, Web of Science and Chinese Biomedical Literature Database, etc., from
      1950 to June 2013. Metadisc1.4 software was used to analyse the pooled
      sensitivity, specificity, diagnostic odds ratio (DOR), and positive and negative
      likelihood ratio. The heterogeneity was assessed using forest plots and the
      inconsistency index (I(2)). Before statistical comparison, the area under (AUC)
      the summary receiver-operating characteristic curve (SROC) of two different
      diagnostic methods was calculated respectively. RESULTS: A total of seven studies
      involving 2,014 patients and 2,666 breast lesions were included. Compared with
      the gold standard (histological results), the pooled sensitivity and specificity
      of DBT were 90.0% and 79.0%, and for DM they were 89.0% and 72.0%, respectively.
      The pooled positive likelihood ratio of DBT and DM was 3.50 and 2.83; the pooled
      negative likelihood ratio of DBT and DM was 15% and 18%; the pooled DOR for DBT
      and DM was 26.04 and 16.24, respectively. CONCLUSIONS: Digital breast
      tomosynthesis has a higher sensitivity and specificity in breast diagnosis than
      digital mammography. KEY POINTS: * Digital breast tomosynthesis has high
      sensitivity and specificity in breast diagnosis.* DBT appears to have superior
      diagnostic accuracy relative to digital mammography. * DBT images were captured
      at a lower dose than 2D images. * DBT displays abnormal features of lesions more
      clearly than DM. * Digital breast tomosynthesis could become the first choice for
      assessing breast lesions.

PMID- 24121713
TI  - Adult exposures from MDCT including multiphase studies: first Italian nationwide
      survey.
AB  - OBJECTIVES: To evaluate the radiation dose in routine multidetector computed
      tomography (MDCT) examinations in Italian population. METHODS: This was a
      retrospective multicentre study included 5,668 patients from 65 radiology
      departments who had undergone common CT protocols: head, chest, abdomen, chest
      abdomen-pelvis (CAP), spine and cardiac. Data included patient characteristics,
      CT parameters, volumetric CT dose index (CTDIvol) and dose length product (DLP)
      for each CT acquisition phase. Descriptive statistics were calculated, and a
      multi-regression analysis was used to outline the main factors affecting
      exposure. RESULTS: The 75th percentiles of CTDIvol (mGy) and DLP (mGy cm) for
      whole head were 69 mGy and 1,312 mGy cm, respectively; for chest, 15 mGy and 569
      mGy cm; spine, 42 mGy and 888 mGy cm; cardiac, 7 mGy and 131 mGy cm for calcium
      score, and 61 mGy and 1,208 mGy cm for angiographic CT studies. High variability
      was present in the DLP of abdomen and CAP protocols, where multiphase
      examinations dominated (71 % and 73 % respectively): for abdomen, 18 mGy, with
      555 and 920 mGy cm in abdomen and abdomen-pelvis acquisitions respectively; for
      CAP, 17 mGy, with 508, 850 and 1,200 mGy cm in abdomen, abdomen-pelvis and CAP
      acquisitions respectively. CONCLUSION: The results of this survey could help in
      the definition of updated diagnostic reference levels (DRL). KEY POINTS: *
      Radiation dose associated with multidetector CT (MDCT) is an important health
      issue. * This national survey assessed dose exposures of 5,668 patients
      undergoing MDCT. * Dose indices correlate with BMI, voltage, rotation time, pitch
      and tube current. * These results may contribute to an update of national
      diagnostic reference levels.

PMID- 24121714
TI  - Zn(II) chloride-catalyzed direct coupling of various alkynes with acetals: facile
      and inexpensive access to functionalized propargyl ethers.
AB  - The coupling of acetals with various alkynes was achieved using only 1 mol% of
      inexpensive and mild Lewis acid ZnCl2, which furnished propargyl ethers. The
      coupling was catalyzed by Zn(OMe)Cl, which was generated in situ to form an
      alkynylzinc species. This protocol was allowed to expand to a one-pot subsequent
      reaction with allylchlorosilane to obtain a 1,4-enyne product. 

PMID- 24121716
TI  - Hydrogen peroxide produced by glucose oxidase affects the performance of laccase
      cathodes in glucose/oxygen fuel cells: FAD-dependent glucose dehydrogenase as a
      replacement.
AB  - Hydrogen peroxide production by glucose oxidase (GOx) and its negative effect on
      laccase performance have been studied. Simultaneously, FAD-dependent glucose
      dehydrogenase (FAD-GDH), an O2-insensitive enzyme, has been evaluated as a
      substitute. Experiments focused on determining the effect of the side reaction of
      GOx between its natural electron acceptor O2 (consumed) and hydrogen peroxide
      (produced) in the electrolyte. Firstly, oxygen consumption was investigated by
      both GOx and FAD-GDH in the presence of substrate. Relatively high
      electrocatalytic currents were obtained with both enzymes. O2 consumption was
      observed with immobilized GOx only, whilst O2 concentration remained stable for
      the FAD-GDH. Dissolved oxygen depletion effects on laccase electrode performances
      were investigated with both an oxidizing and a reducing electrode immersed in a
      single compartment. In the presence of glucose, dramatic decreases in cathodic
      currents were recorded when laccase electrodes were combined with a GOx-based
      electrode only. Furthermore, it appeared that the major loss of performance of
      the cathode was due to the increase of H2O2 concentration in the bulk solution
      induced laccase inhibition. 24 h stability experiments suggest that the use of O2
      insensitive FAD-GDH as to obviate in situ peroxide production by GOx is
      effective. Open-circuit potentials of 0.66 +/- 0.03 V and power densities of
      122.2 +/- 5.8 MUW cm(-2) were observed for FAD-GDH/laccase biofuel cells. 

PMID- 24121715
TI  - Biaxial normal strength behavior in the axial-transverse plane for human
      trabecular bone--effects of bone volume fraction, microarchitecture, and
      anisotropy.
AB  - The biaxial failure behavior of the human trabecular bone, which has potential
      relevance both for fall and gait loading conditions, is not well understood,
      particularly for low-density bone, which can display considerable mechanical
      anisotropy. Addressing this issue, we investigated the biaxial normal strength
      behavior and the underlying failure mechanisms for human trabecular bone
      displaying a wide range of bone volume fraction (0.06-0.34) and elastic
      anisotropy. Micro-computed tomography (CT)-based nonlinear finite element
      analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes),
      spanning the complete biaxial normal stress failure space in the axial-transverse
      plane. The specimens, treated as approximately transversely isotropic, were
      loaded in the principal material orientation. We found that the biaxial stress
      yield surface was well characterized by the superposition of two ellipses--one
      each for yield failure in the longitudinal and transverse loading directions--and
      the size, shape, and orientation of which depended on bone volume fraction and
      elastic anisotropy. However, when normalized by the uniaxial tensile and
      compressive strengths in the longitudinal and transverse directions, all of which
      depended on bone volume fraction, microarchitecture, and mechanical anisotropy,
      the resulting normalized biaxial strength behavior was well described by a single
      pair of (longitudinal and transverse) ellipses, with little interspecimen
      variation. Taken together, these results indicate that the role of bone volume
      fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in
      determining the uniaxial strength behavior and the effect of these parameters on
      the axial-transverse biaxial normal strength behavior per se is minor.

PMID- 24121717
TI  - A two-photon ratiometric fluorescence probe for cupric ions in live cells and
      tissues.
AB  - Development of sensitive and selective probes for cupric ions (Cu(2+)) at cell
      and tissue level is a challenging work for progress in understanding the
      biological effects of Cu(2+). Here, we report a ratiometric two-photon probe for
      Cu(2+) based on the organic-inorganic hybrids of graphene quantum dots (GQDs) and
      Nile Blue dye. Meanwhile, Cu-free derivative of copper-zinc superoxide dismutase
      (SOD) - E2Zn2SOD is designed as the unique receptor for Cu(2+) and conjugated on
      the surface of GQDs. This probe shows a blue-to-yellow color change in repose to
      Cu(2+), good selectivity, low cytotoxicity, long-term photostability, and
      insensitivity to pH over the biologically relevant pH range. The developed probe
      allows the direct visualization of Cu(2+) levels in live cells as well as in deep
      tissues at 90-180 MUm depth through the use of two-photon microscopy.
      Furthermore, the effect of ascorbic acid is also evaluated on intracellular
      Cu(2+) binding to E2Zn2SOD by this probe.

PMID- 24121719
TI  - 5-Aminotetrazole induces spin crossover in iron(III) pentadentate Schiff base
      complexes: experimental and theoretical investigations.
AB  - A series of novel mononuclear iron(III) complexes [Fe(saldpt)(atz)] (1) and
      [Fe(Rsalpet)(atz)] (2a-d) involving 5-aminotetrazole (Hatz) and pentadentate
      Schiff base ligands (H2saldpt = N,N'-bis(2-hydroxybenzyliden)-1,7-diamino-4
      azaheptane, H2salpet = N,N'-bis(2-hydroxybenzyliden)-1,6-diamino-3-azahexane,
      H25Cl-salpet = N,N'-bis(5-chloro-2-hydroxybenzylidene)-1,6-diamino-3-azahexane,
      H25Br-salpet = N,N'-bis(5-bromo-2-hydroxybenzylidene)-1,6-diamino-3-azahexane and
      H23,5Br-salpet = N,N'-bis(3,5-dibromo-2-hydroxybenzylidene)-1,6-diamino-3
      azahexane) was prepared and characterized by elemental analysis, FTIR
      spectroscopy, mass spectrometry, single crystal X-ray analysis, magnetic
      measurements and (57)Fe Mossbauer spectroscopy. In contrast to the high-spin
      magnetic properties of [Fe(saldpt)(atz)] (1), the complexes [Fe(Rsalpet)(atz)]
      (2a-d) undergo spin crossover with critical temperatures above 416 K.
      Furthermore, DFT calculations with the B3LYP functional were employed to
      investigate the effect of the conductor-like screening model (COSMO) and van der
      Waals corrections (VDW) as well as relativistic effects with the scalar
      relativistic second-order Douglas-Kroll-Hess Hamiltonian (DKH2) on low-spin and
      high-spin molecular geometries and thus on spin crossover parameters (enthalpy,
      entropy and critical temperature).

PMID- 24121718
TI  - Short-term effects of military fog oil on the fountain darter (Etheostoma
      fonticola).
AB  - Toxicity tests evaluated chronic and sublethal effects of fog oil (FO) on a
      freshwater endangered fish. FO is released during military training as an
      obscurant smoke that can drift into aquatic habitats. Fountain darters,
      Etheostoma fonticola, of four distinct life stages were exposed under laboratory
      conditions to three forms of FO. FO was vaporized into smoke and allowed to
      settle onto water, violently agitated with water, and dosed onto water followed
      by photo-oxidization by ultraviolet irradiation. Single smoke exposures of
      spawning adult fish did not affect egg production, egg viability, or adult fish
      survival in 21-day tests. Multiple daily smoke exposures induced mortality after
      5 days for larvae fish. Larvae and juvenile fish were more sensitive than eggs in
      96-h lethal concentration (LC50) tests with FO-water mixtures and photo-oxidized
      FO. Water-soluble FO components photo-modified by ultraviolet radiation were the
      most toxic, thus indicating the value of examining weathering and aging of
      chemicals for the best determination of environmental impact.

PMID- 24121720
TI  - Analysis of mitochondrial genome diversity identifies new and ancient maternal
      lineages in Cambodian aborigines.
AB  - Cambodia harbours a variety of aboriginal (and presumably ancient) populations
      that have largely been ignored in studies of genetic diversity. Here we
      investigate the matrilineal gene pool of 1,054 Cambodians from 14 geographic
      populations. Using mitochondrial whole-genome sequencing, we identify eight new
      mitochondrial DNA haplogroups, all of which are either newly defined basal
      haplogroups or basal sub-branches. Most of the new basal haplogroups have very
      old coalescence ages, ranging from ~55,000 to ~68,000 years, suggesting that
      present-day Cambodian aborigines still carry ancient genetic polymorphisms in
      their maternal lineages, and most of the common Cambodian haplogroups probably
      originated locally before expanding to the surrounding areas during prehistory.
      Moreover, we observe a relatively close relationship between Cambodians and
      populations from the Indian subcontinent, supporting the earliest costal route of
      migration of modern humans from Africa into mainland Southeast Asia by way of the
      Indian subcontinent some 60,000 years ago. 

PMID- 24121721
TI  - Suicide mortality in second-generation migrants, Australia,  2001-2008.
AB  - PURPOSE: Generally, due to limited availability of official statistics on the
      topic, little is known about suicide mortality in second-generation migrants. A
      recent study from Sweden showed that these people could be at a high suicide
      risk. In a generalised phenomenon, this aspect would represent an important issue
      in suicide prevention. This paper aims to report the profile of second-generation
      migrants who died by suicide and the suicide risk differentials of second
      generation migrants with other Australians. METHODS: Official suicide data from
      2001 to 2008 were linked with State/Territory registries to collect information
      about the birthplace of the deceased's parents to differentiate migration status
      (first, second or third-plus generation). The profile and suicide risk of second
      generation migrants were compared with other generations by logistic and Poisson
      regression. RESULTS: Suicide in second-generation migrants accounted for 811
      cases (14.6%). These tended to be represented by younger subjects, more often
      never married, as compared to the other cases. Second-generation males aged 25-39
      years tended to have a higher suicide risk than first generation migrants, but
      the risk was lower when compared with the third-plus generation. Second
      generation migrants aged 60? tended to have a lower suicide risk than first
      generation migrants. CONCLUSION: In Australia, second-generation migrants are not
      at a higher suicide risk as compared to first-generation migrants or locals
      (third-plus-generation). In males aged 25-39, a lower suicide risk was found in
      second-generations as compared to Australian-born third generation,which may be
      explained by their more advantageous socioeconomic status and the flexibility and
      resources rendered by having grown up in a bicultural environment.The higher
      suicide rates found amongst older first-generation migrants require further
      examination.

PMID- 24121722
TI  - Segmental tracheal resection for invasive differentiated thyroid carcinoma. Our
      experience in eight cases.
AB  - PURPOSE: In differentiated thyroid carcinoma (DTC), complete resection of local
      disease provides the longest survival and the best palliation. In pursuit of this
      goal, segmental tracheal or laryngotracheal resection can be performed on
      patients with DTC invading the airway. The study summarizes the technical aspects
      of the intervention and analyzes its results in eight patients. METHODS: The
      results of eight tracheal or laryngotracheal resections for DTC invading the
      airway were analyzed. Three patients presented with local recurrent disease,
      whereas five underwent airway resection at the time of thyroidectomy or shortly
      after. All received a circumferential sleeve resection of the trachea (2-4
      tracheal rings) that in three cases extended to the cricoid, followed by end-to
      end anastomosis. RESULTS: Pathologic evaluation identified seven papillary and
      one poorly differentiated carcinomas. No postoperative deaths occurred; one
      patient required surgical reexploration because of postoperative bleeding, and
      two air leaks resolved with conservative treatment. Functional results were
      excellent. During follow-up, one patient died of lung and bone metastases, while
      in two cases locally persistent/recurrent disease has been detected; two patients
      are currently free of disease, and in the last three cases only persistent
      thyroglobulin levels are indicative of residual disease. CONCLUSIONS: In our
      experience, segmental airway resection is safe, provides excellent functional
      results, and can warrant adequate control of local disease.

PMID- 24121725
TI  - Temporal quantification of MAPK induced expression in single yeast cells.
AB  - The quantification of gene expression at the single cell level uncovers novel
      regulatory mechanisms obscured in measurements performed at the population level.
      Two methods based on microscopy and flow cytometry are presented to demonstrate
      how such data can be acquired. The expression of a fluorescent reporter induced
      upon activation of the high osmolarity glycerol MAPK pathway in yeast is used as
      an example. The specific advantages of each method are highlighted. Flow
      cytometry measures a large number of cells (10,000) and provides a direct measure
      of the dynamics of protein expression independent of the slow maturation kinetics
      of the fluorescent protein. Imaging of living cells by microscopy is by contrast
      limited to the measurement of the matured form of the reporter in fewer cells.
      However, the data sets generated by this technique can be extremely rich thanks
      to the combinations of multiple reporters and to the spatial and temporal
      information obtained from individual cells. The combination of these two
      measurement methods can deliver new insights on the regulation of protein
      expression by signaling pathways. 

PMID- 24121726
TI  - A 4-coordinate Ru(II) imido: unusual geometry, synthesis, and reactivity.
AB  - A 4-coordinate Ru(II) imido complex, Ru(NAr)(PMe3)3 (1), can be prepared from cis
      RuCl2(PMe3)4 and LiNHAr. The structure of the imido is perhaps best described as
      a flat-based trigonal pyramid with the imido in the equatorial plane. A possible
      explanation for the unusual geometry is discussed, along with some reactivity of
      1.

PMID- 24121723
TI  - Immunopathogenesis of abdominal sepsis.
AB  - BACKGROUND: Sepsis is an unsolved problem worldwide, with a 30-50 % mortality
      rate. The recent failures of anti-TLR4, recombinant activated protein C, and anti
      TNF in clinical trials indicate a need to rethink our current understanding of
      sepsis's pathophysiology. While the initial immune response is crucial for
      effective clearance of invading pathogens, an overly exuberant host response to
      infection can cause septic shock, tissue damage, and death. Profuse inflammation
      in sepsis is frequently followed by global immunosuppression that increases
      susceptibility to viral and bacterial infections. Despite the dangers of immune
      over-response, the immune system's anti-inflammatory activities are likely
      necessary to reduce the initial over-activation of the immune system. PURPOSE:
      With this review, we want to illuminate the different aspects of immune response
      to sepsis and provide insight to the ongoing difficulties currently present
      within sepsis research. CONCLUSION: Future treatment strategies for sepsis should
      focus on maintaining balance between pro- and anti-inflammatory immune actions in
      a timely manner.

PMID- 24121727
TI  - Using Strahler's analysis to reduce up to 200-fold the run time of realistic
      neuron models.
AB  - The cellular mechanisms underlying higher brain functions/dysfunctions are
      extremely difficult to investigate experimentally, and detailed neuron models
      have proven to be a very useful tool to help these kind of investigations.
      However, realistic neuronal networks of sizes appropriate to study brain
      functions present the major problem of requiring a prohibitively high
      computational resources. Here, building on our previous work, we present a
      general reduction method based on Strahler's analysis of neuron morphologies. We
      show that, without any fitting or tuning procedures, it is possible to map any
      morphologically and biophysically accurate neuron model into an equivalent
      reduced version. Using this method for Purkinje cells, we demonstrate how run
      times can be reduced up to 200-fold, while accurately taking into account the
      effects of arbitrarily located and activated synaptic inputs. 

PMID- 24121728
TI  - Reactive oxygen species production by catechol stabilized copper nanoparticles.
AB  - Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based
      linkers could generate reactive oxygen species (ROS) that can activate peroxidase
      enzymes and catalyze the degradation of fluorescent dye pollutants. 

PMID- 24121729
TI  - Epistasis in iron metabolism: complex interactions between Cp, Mon1a, and Slc40a1
      loci and tissue iron in mice.
AB  - Disorders of iron metabolism are among the most common acquired and constitutive
      diseases. Hemochromatosis has a solid genetic basis and in Northern European
      populations it is usually associated with homozygosity for the C282Y mutation in
      the HFE protein. However, the penetrance of this mutation is incomplete and the
      clinical presentation is highly variable. The rare and common variants identified
      so far as genetic modifiers of HFE-related hemochromatosis are unable to account
      for the phenotypic heterogeneity of this disorder. There are wide variations in
      the basal iron status of common inbred mouse strains, and this diversity may
      reflect the genetic background of the phenotypic diversity under pathological
      conditions. We therefore examined the genetic basis of iron homeostasis using
      quantitative trait loci mapping applied to the HcB-15 recombinant congenic
      strains for tissue and serum iron indices. Two highly significant QTL containing
      either the N374S Mon1a mutation or the Ferroportin locus were found to be major
      determinants in spleen and liver iron loading. Interestingly, when considering
      possible epistatic interactions, the effects of Mon1a on macrophage iron export
      are conditioned by the genotype at the Slc40a1 locus. Only mice that are
      C57BL/10ScSnA homozygous at both loci display a lower spleen iron burden.
      Furthermore, the liver-iron lowering effect of the N374S Mon1a mutation is
      observed only in mice that display a nonsense mutation in the Ceruloplasmin (Cp)
      gene. This study highlights the existence of genetic interactions between Cp,
      Mon1a, and the Slc40a1 locus in iron metabolism, suggesting that epistasis may be
      a crucial determinant of the variable biological and clinical presentations in
      iron disorders.

PMID- 24121731
TI  - General equation for the differential pathlength factor of the frontal human head
      depending on wavelength and age.
AB  - Continuous-wave near-infrared spectroscopy and near-infrared imaging enable the
      measurement of relative concentration changes in oxy- and deoxyhemoglobin and
      thus hemodynamics and oxygenation. The accuracy of determined changes depends
      mainly on the modeling of the light transport through the probed tissue. Due to
      the highly scattering nature of tissue, the light path is longer than the source
      detector separation (d). This is incorporated in modeling by multiplying d by a
      differential pathlength factor (DPF) which depends on several factors such as
      wavelength, age of the subject, and type of tissue. In the present work, we
      derive a general DPF equation for the frontal human head, incorporating
      dependency on wavelength and age, based on published data. We validated the
      equation using different data sets of experimentally determined DPFs from six
      independent studies.

PMID- 24121732
TI  - Fiber-optic probe design and optical property recovery algorithm for optical
      biopsy of brain tissue.
AB  - Optical biopsy techniques offer a minimally invasive, real-time alternative to
      traditional biopsy and pathology during tumor resection surgery. Diffuse
      reflectance spectroscopy (DRS) is a commonly used technique in optical biopsy.
      Optical property recovery from spatially resolved DRS data allows quantification
      of the scattering and absorption properties of tissue. Monte Carlo simulation
      methods were used to evaluate a unique fiber-optic probe design for a DRS
      instrument to be used specifically for optical biopsy of the brain. The probe
      diameter was kept to a minimum to allow usage in small surgical cavities at least
      1 cm in diameter. Simulations showed that the close proximity of fibers to the
      edge of the probe resulted in boundary effects due to reflection of photons from
      the surrounding air-tissue interface. A new algorithm for rapid optical property
      recovery was developed that accounts for this reflection and therefore overcomes
      these effects. The parameters of the algorithm were adjusted for use over the
      wide range of optical properties encountered in brain tissue, and its precision
      was evaluated by subjecting it to random noise. This algorithm can be adapted to
      work with any probe geometry to allow optical property recovery in small surgical
      cavities.

PMID- 24121730
TI  - Ventricular performance after surgery for a congenital heart defect as assessed
      using advanced echocardiography: from doppler flow to 3D echocardiography and
      speckle-tracking strain imaging.
AB  - A varying degree of impairment of ventricular performance is observed over the
      long-term after surgery for a congenital heart defect (CHD). Impaired ventricular
      performance has been shown to be of prognostic value for increased risk of
      cardiovascular events in adult CHD patients. This emphasizes the importance of
      delineating the timing and cause of this postoperative impairment. Impairment of
      ventricular performance could develop over time as a consequence of residua,
      sequelae and complications of the CHD or surgical procedure. Yet, impaired
      ventricular performance has also been observed immediately after surgery and can
      persist and/or worsen over time. This postoperative impairment of ventricular
      performance is the focus of this review. This article provides an overview of
      echocardiographic techniques currently used to assess ventricular performance.
      Furthermore, we review current literature describing ventricular performance, as
      assessed using echocardiography, after correction of a CHD. In general, a
      decrease in ventricular performance is observed directly after surgery for CHD's.
      Subsequent follow-up of ventricular performance is characterized by a varying
      degree of postoperative recovery. A consistent observation is the persistent
      impairment of right-ventricular performance after repair in several different
      subgroups of CHD patients ranging from ventricular septal defect repair to
      surgery for Tetralogy of Fallot.

PMID- 24121733
TI  - Hollow palladium nanospheres with porous shells supported on graphene as enhanced
      electrocatalysts for formic acid oxidation.
AB  - The hollow palladium nanospheres with the porous shell comprised of uniform 5 nm
      Pd nanoparticles (Pd NS-HP) have been synthesized successfully by employing a
      simple replacement process between PdCl4(2-) ions and Co with the assistance of a
      structure-directing agent, polyvinyl pyrrolidone (PVP). Then, the obtained Pd NS
      HP is supported on graphene nanosheets (GN) to prepare Pd NS-HP/GN composites by
      a wet-impregnation method. As the catalyst towards formic acid electrooxidation,
      the Pd NS-HP/GN composite exhibits a larger electrochemically active surface
      area, better electrocatalytic activity and better stability compared with Pd
      nanoparticles/graphene (Pd NP/GN) and commercial Pd/C catalysts. The enhancement
      in electrocatalytic performance of Pd NS-HP/GN is attributed to the abundant
      connected pore channels in the inner and exterior surfaces of Pd nanospheres,
      which could provide a large contact surface for adsorption and transmission of
      reactants, facilitating the oxidation of formic acid molecules on its surface and
      also improving the utilization of Pd metal. Moreover, the support of graphene
      could enhance the stability of the catalyst. 

PMID- 24121734
TI  - Combined surgical and interventional radiologic management strategies in patients
      with arterial pseudo-aneurysms after multivisceral transplantation.
AB  - BACKGROUND: Multivisceral transplantation has recently evolved to be a life
      saving procedure for patients with intestinal failure and complex abdominal
      pathology. A composite aortic graft is always needed to restore the arterial flow
      to the transplanted organs. Accordingly, arterial complications can be life
      threatening requiring prompt intervention. Herein, we describe innovative
      technical approaches in seven recipients who developed pseudo-aneurysm (PA) after
      transplantation. METHODS: With a total of 285 composite visceral transplants, 15
      (5.2%) patients experienced vascular complications. Of these, 7 were life
      threatening PAs that were diagnosed 61 to 2677 days after transplantation. Due to
      the anatomic and technical complexity of the allograft vasculature, endovascular
      techniques were introduced alone (n=2) or in conjunction with surgical
      intervention (n=5) in an attempt to rescue patients and salvage the transplanted
      organs. RESULTS: The endovascular and surgical technical approaches used for each
      of the 7 PA actively bleeding patients was successful in 5 (71%). Of these, 2
      (40%) are alive 86 to 117 months after the intervention. The remaining 5
      recipients died of recurrent hemorrhage (n=2), liver failure (n=1), and pneumonia
      (n=1). The cause of death was unknown in the remaining patient. Retransplantation
      and intra-abdominal infections were major risk factors. Candida was the most
      common isolated microorganism. CONCLUSIONS: Recipients of composite visceral
      allografts are at risk of developing life-threatening PAs, particularly in those
      with early posttransplantation abdominal infections. Prompt multidisciplinary
      diagnosis and therapeutic approaches are crucial management strategies.

PMID- 24121736
TI  - Recent advances in lanthanide-doped upconversion nanomaterials: synthesis,
      nanostructures and surface modification.
AB  - Owing to their unique photo-physical properties, rare-earth ions-doped
      upconversion nanoparticles (UCNPs) have attracted extensive attention in recent
      years. UCNPs have many special merits, such as a long luminescence lifetime,
      narrow emission band widths, high quantum yields and low toxicity, which allows
      their potential applications in bio-medical field, biological luminescent labels
      and drug delivery carriers. Compared with traditional fluorescence labels exited
      by UV (ultraviolet), such as organic dyes and quantum dots, UCNPs can transfer
      near-infrared (NIR) light into visible light, which is commonly called
      upconversion luminescence (UCL). This paper reviews the recent advances of
      several typical synthesis methods of UCNPs in detail as well as the fabrication
      and optimization of the particle morphology, and the latest advances of UCNPs for
      multimode imaging, surface passivation and functionalization are also described. 

PMID- 24121735
TI  - Laparoscopic ventral hernia repair: is there an optimal mesh fixation technique?
      A systematic review.
AB  - PURPOSE: The purpose of this study is to distinguish the optimal mesh fixation
      technique used in laparoscopic ventral hernia repair (LVHR). A particular
      fixation technique of the mesh to the abdominal wall is required, which should be
      strong enough to prevent migration of the mesh and, at the same time, keep injury
      to the abdominal wall minimal to prevent postoperative discomfort and pain.
      METHODS: An extensive literature search was performed in the PubMed database from
      its onset until November 2012. All series of at least 30 patients operated by
      laparoscopy for a ventral hernia, with the use of a standardized surgical
      technique well-defined in the "Methods" section, and with a follow-up of at least
      12 months were included. The series were categorized according to the technique
      of mesh fixation described: "tacks and sutures," "tacks only," and "sutures
      only." For each treatment group, the recurrence rate was adjusted to the number
      of patients treated and the 95 % confidence interval was calculated. No overlap
      between two intervals was defined as a significant difference in recurrence rate.
      RESULTS: A total of 25 series were included for statistical evaluation. Thirteen
      trials used both tacks and sutures, ten used only tacks, and two used only
      sutures. Overall recurrence rate was 2.7 % (95 % CI [1.9-3.4 %]). CONCLUSION:
      None of the currently available mesh fixation techniques used for LVHR was found
      to be superior in preventing hernia recurrence as well as in reducing abdominal
      wall pain. The pain reported was remarkably high with all different fixation
      devices. Further research to develop solid and atraumatic fixation devices is
      warranted.

PMID- 24121739
TI  - A new design for nucleolipid-based Ru(III) complexes as anticancer agents.
AB  - In continuation with our studies concerning the synthesis, characterization and
      biological evaluation of nucleolipidic Ru(III) complexes, a novel design for this
      family of potential anticancer agents is presented here. As a model compound, a
      new uridine-based nucleolipid has been prepared, named HoUrRu, following a simple
      and versatile synthetic procedure, and converted into a Ru(III) salt. Stable
      formulations of this highly functionalized Ru(III) complex have been obtained by
      co-aggregation with either the zwitterionic lipid POPC or the cationic DOTAP,
      which have been subjected to an in-depth microstructural characterization,
      including DLS, SANS and EPR measurements. The in vitro bioactivity profile of
      HoUrRu, as a pure compound or in formulation with POPC or DOTAP, reveals high
      antiproliferative activity against MCF-7 and WiDr human cancer cell lines.

PMID- 24121737
TI  - Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain
      levels of kynurenic acid.
AB  - In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors
      (alpha7nAChRs) modulate effects of Delta(9)-tetrahydrocannabinol (THC),
      marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous
      negative allosteric modulator of alpha7nAChRs. Here we report that the kynurenine
      3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and
      attenuates cannabinoid-induced increases in extracellular dopamine in reward
      related brain areas. In the self-administration model of drug abuse, Ro 61-8048
      reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2
      in squirrel monkeys and rats, respectively, and it also prevented relapse to drug
      seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The
      effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by
      positive allosteric modulators of alpha7nAChRs. Despite a clear need, there are
      no medications approved for treatment of marijuana dependence. Modulation of KYNA
      offers a pharmacological strategy for achieving abstinence from marijuana and
      preventing relapse. 

PMID- 24121740
TI  - Effect of Copper, Irgarol and Atrazine on Epiphytes Attached to Artificial
      Devices for Coastal Ecotoxicology Bioassays.
AB  - Toxic effects of copper, atrazine and irgarol were evaluated on epiphytes
      attached to mimes (artificial devices that mimic the morphology of seagrasses) in
      order to check sensitivity of this biological group. Tube-dwelling diatoms were
      the major component of the epiphyte community. Superoxide dismutase activity was
      enhanced by exposure to 25 and 50 MUg L-1 of atrazine; the organism generates
      this antioxidant response to prevent cellular damage by removing reactive oxygen
      substances produced by oxidative stress. The measurement of antioxidant enzymatic
      activity in epiphytes could be a useful technique for ecotoxicology monitoring in
      marine coastal environments.

PMID- 24121738
TI  - Age-dependent regulation of synaptic connections by dopamine D2 receptors.
AB  - Dopamine D2 receptors (D2R) are G protein-coupled receptors that modulate
      synaptic transmission and are important for various brain functions, including
      learning and working memory. Abnormal D2R signaling has been implicated in
      psychiatric disorders such as schizophrenia. Here we report a new function of D2R
      in dendritic spine morphogenesis. Activation of D2R reduced spine number via
      GluN2B- and cAMP-dependent mechanisms in mice. Notably, this regulation occurred
      only during adolescence. During this period, D2R overactivation caused by
      mutations in the schizophrenia risk gene Dtnbp1 led to spine deficiency,
      dysconnectivity in the entorhinal-hippocampal circuit and impairment of spatial
      working memory. Notably, these defects could be ameliorated by D2R blockers
      administered during adolescence. Our findings suggest an age-dependent function
      of D2R in spine development, provide evidence that D2R dysfunction during
      adolescence impairs neuronal circuits and working memory, and indicate that
      adolescent interventions to prevent aberrant D2R activity protect against
      cognitive impairment. 

PMID- 24121741
TI  - Degradation of clodinafop propargyl by Pseudomonas sp. strain B2.
AB  - Using clodinafop propargyl (CF) as a sole carbon, nitrogen and energy source, a
      CF-degrading bacterial strain was isolated from crop soil field. This strain was
      identified as Pseudomonas sp. strain B2 by 16S rRNA gene sequence analysis. 87.14
      % CF was degraded out of initial provided 80 mg/L CF. Degradation of CF was
      accompanied by release of chloride ion. The optimal pH and temperature for the
      growth of B2 were 7.0 and 30 degrees C, respectively in the mineral salts medium
      supplemented with CF. An actively growing culture of strain B2 degraded CF to
      clodinafop acid and 4-(4-Chloro-2-fluoro-phenoxy)-phenol within 9 h, as
      determined by GC-MS analysis. A metabolic pathway for the degradation of CF by B2
      has been proposed

PMID- 24121742
TI  - Intraductal injection for localized drug delivery to the mouse mammary gland.
AB  - Herein we describe a protocol to deliver various reagents to the mouse mammary
      gland via intraductal injections. Localized drug delivery and knock-down of genes
      within the mammary epithelium has been difficult to achieve due to the lack of
      appropriate targeting molecules that are independent of developmental stages such
      as pregnancy and lactation. Herein, we describe a technique for localized
      delivery of reagents to the mammary gland at any stage in adulthood via
      intraductal injection into the nipples of mice. The injections can be performed
      on live mice, under anesthesia, and allow for a non-invasive and localized drug
      delivery to the mammary gland. Furthermore, the injections can be repeated over
      several months without damaging the nipple. Vital dyes such as Evans Blue are
      very helpful to learn the technique. Upon intraductal injection of the blue dye,
      the entire ductal tree becomes visible to the eye. Furthermore, fluorescently
      labeled reagents also allow for visualization and distribution within the mammary
      gland. This technique is adaptable for a variety of compounds including siRNA,
      chemotherapeutic agents, and small molecules. 

PMID- 24121743
TI  - [C70] fullerene-sensitized triplet-triplet annihilation upconversion.
AB  - We herein report the first instance of using pristine C70 as a heavy-atom free
      organic sensitizer for efficient triplet-triplet annihilation upconversion (UC)
      for both green-to-blue and red-to-green UC using 9,10
      bis(phenylethynyl)anthracene and perylene as acceptors, respectively. C70
      achieved quantum yields of 8% and 0.8% for green-to-blue and red-to-green UC, 25
      to 35 times higher than C60, and showed improved stability under continuous laser
      irradiation compared to the benchmark platinum(II)-octaethylporphyrin.

PMID- 24121744
TI  - Evaluation of a new high-throughput method for identifying quorum quenching
      bacteria.
AB  - Quorum sensing (QS) is a population-dependent mechanism for bacteria to
      synchronize social behaviors such as secretion of virulence factors. The
      enzymatic interruption of QS, termed quorum quenching (QQ), has been suggested as
      a promising alternative anti-virulence approach. In order to efficiently identify
      QQ bacteria, we developed a simple, sensitive and high-throughput method based on
      the biosensor Agrobacterium tumefaciens A136. This method effectively eliminates
      false positives caused by inhibition of growth of biosensor A136 and alkaline
      hydrolysis of N-acylhomoserine lactones (AHLs), through normalization of beta
      galactosidase activities and addition of PIPES buffer, respectively. Our novel
      approach was successfully applied in identifying QQ bacteria among 366 strains
      and 25 QQ strains belonging to 14 species were obtained. Further experiments
      revealed that the QQ strains differed widely in terms of the type of QQ enzyme,
      substrate specificity and heat resistance. The QQ bacteria identified could
      possibly be used to control disease in aquaculture.

PMID- 24121746
TI  - Overviews'' should meet the methodological standards of systematic reviews.

PMID- 24121745
TI  - A novel liquid chromatography/tandem mass spectrometry method for the
      quantification of glycine as biomarker in brain microdialysis and cerebrospinal
      fluid samples within 5min.
AB  - Glycine is an important amino acid neurotransmitter in the central nervous system
      (CNS) and a useful biomarker to indicate biological activity of drugs such as
      glycine reuptake inhibitors (GRI) in the brain. Here, we report how a liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) method for the fast and
      reliable analysis of glycine in brain microdialysates and cerebrospinal fluid
      (CSF) samples has been established. Additionally, we compare this method with the
      conventional approach of high performance liquid chromatography (HPLC) coupled to
      fluorescence detection (FD). The present LC-MS/MS method did not require any
      derivatisation step. Fifteen microliters of sample were injected for analysis.
      Glycine was detected by a triple quadrupole mass spectrometer in the positive
      electrospray ionisation (ESI) mode. The total running time was 5min. The limit of
      quantitation (LOQ) was determined as 100nM, while linearity was given in the
      range from 100nM to 100MUM. In order to demonstrate the feasibility of the LC
      MS/MS method, we measured glycine levels in striatal in vivo microdialysates and
      CSF of rats after administration of the commercially available glycine
      transporter 1 (GlyT1) inhibitor LY 2365109 (10mg/kg, p.o.). LY 2365109 produced 2
      fold and 3-fold elevated glycine concentrations from 1.52MUM to 3.6MUM in
      striatal microdialysates and from 10.38MUM to 36MUM in CSF, respectively. In
      conclusion, we established a fast and reliable LC-MS/MS method, which can be used
      for the quantification of glycine in brain microdialysis and CSF samples in
      biomarker studies. 

PMID- 24121747
TI  - Comment on Abdallah et al. entitled ''body mass index and risk of surgical site
      infection following spine surgery: a meta-analysis''.

PMID- 24121748
TI  - In vivo biofunctional evaluation of hydrogels for disc regeneration.
AB  - PURPOSE: Regenerative strategies aim to restore the original biofunctionality of
      the intervertebral disc. Different biomaterials are available, which might
      support disc regeneration. In the present study, the prospects of success of two
      hydrogels functionalized with anti-angiogenic peptides and seeded with bone
      marrow derived mononuclear cells (BMC), respectively, were investigated in an
      ovine nucleotomy model. METHODS: In a one-step procedure iliac crest aspirates
      were harvested and, subsequently, separated BMC were seeded on hydrogels and
      implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid
      based hydrogel was used. The anti-angiogenic potential of newly developed VEGF
      blockers was investigated on ionically crosslinked metacrylated gellan gum
      hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep
      were used. After 6 weeks histological, after 12 weeks histological and
      biomechanical analyses were conducted. RESULTS: Biomechanical tests revealed no
      differences between any of the implanted and nucleotomized discs. All implanted
      discs significantly degenerated compared to intact discs. In contrast, there was
      no marked difference between implanted and nucleotomized discs. In tendency,
      albeit not significant, degeneration score and disc height index deteriorated for
      all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded
      hydrogels slightly decelerated degeneration. CONCLUSIONS: None of the hydrogel
      configurations was able to regenerate biofunctionality of the intervertebral
      disc. This might presumably be caused by hydrogel extrusion. Great importance
      should be given to the development of annulus sealants, which effectively exploit
      the potential of (cell-seeded) hydrogels for biological disc regeneration and
      restoration of intervertebral disc functioning.

PMID- 24121749
TI  - Pure percutaneous pedicle screw fixation without arthrodesis of 32 thoraco-lumbar
      fractures: clinical and radiological outcome with 36-month follow-up.
AB  - PURPOSE: To evaluate the outcome of pure percutaneous fixation of unstable single
      level fractures at the thoraco-lumbar junction (A1 to B2 Magerl/AO Spine).
      METHOD: Neurological intact patients were included in a 2-year prospective study
      (follow-up 36 months). Two groups were considered: the group in which additional
      short bilateral screws in the fractured vertebra were placed was called
      lordorizing screw group (LSG), the other was called non lordorizing screw group
      (nLSG). Clinical outcome was evaluated using the SF-36, the Oswestry disability
      index and the recovery time needed to go back work. The following radiological
      parameters were also evaluated on the follow-up exams: the Mid-Sagittal Index,
      the Cobb's angle and the Sagittal Index. RESULTS: In the LSG, the correction
      values of MSI, Cobb's angle and SI were statistically significantly higher than
      in nLSG. CONCLUSION: When feasible we recommend a pure percutaneous short segment
      pedicle screw fixation adding a lordorizing screw.

PMID- 24121750
TI  - Synovial sarcoma of the spine: a case involving paraspinal muscle with extensive
      calcification and the surgical consideration in treatment.
AB  - INTRODUCTION: Synovial sarcoma is a rare malignant tumor of the spine. This tumor
      may present as a painless mass of the spine or slowly enlarge, causing pain or
      neurologic deficits. As it is difficult to differentiate this lesion from other
      soft tissue tumors, synovial sarcoma requires histologic confirmation for
      definite diagnosis. Thus, the treatment strategy is often planned in the final
      step depending on the pathologic results. Despite its rare incidence, a few cases
      of primary or metastatic synovial sarcoma involving the spinal cord, foramen,
      vertebral body, or paraspinal muscles have been reported in the literature.
      MATERIALS AND METHODS: We present the case of a 29-year-old man with a synovial
      sarcoma in the paraspinal muscle of the cervical spine. The patient was evaluated
      radiologically and histologically. Plain radiography, computed tomography, and
      magnetic resonance imaging were performed as part of the preoperative workup, and
      immunohistochemical and cytogenetic studies were additionally performed to
      identify the histologic features of the tumor. The patient underwent marginal
      resection followed by adjuvant radiation therapy. The patient has been followed
      up for 2 years. CONCLUSIONS: This article highlights the features of synovial
      sarcoma of the spine via a comprehensive review. Synovial sarcoma of the spine is
      uncommon, but it is a challenging issue in both diagnostic and therapeutic
      aspects. The currently available evidence suggests the use of a multidisciplinary
      approach in the treatment of synovial sarcoma, which includes complete resection
      and radiation therapy.

PMID- 24121751
TI  - Sleep apnea and cervical spine pathology.
AB  - PURPOSE: Sleep apnea is a multi-factorial disease with a variety of identified
      causes. With its close proximity to the upper airway, the cervical spine and its
      associated pathologies can produce sleep apnea symptoms in select populations.
      The aim of this article was to summarize the literature discussing how cervical
      spine pathologies may cause sleep apnea. METHODS: A search of the PubMed database
      for English-language literature concerning the cervical spine and its
      relationship with sleep apnea was conducted. Seventeen published papers were
      selected and reviewed. RESULTS: Single-lesion pathologies of the cervical spine
      causing sleep apnea include osteochondromas, osteophytes, and other rare
      pathologies. Multifocal lesions include rheumatoid arthritis of the cervical
      spine and endogenous cervical fusions. Furthermore, occipital-cervical
      misalignment pre- and post-cervical fusion surgery may predispose patients to
      sleep apnea. CONCLUSIONS: Pathologies of the cervical spine present significant
      additional etiologies for producing obstructive sleep apnea in select patient
      populations. Knowledge of these entities and their pathophysiologic mechanisms is
      informative for the clinician in diagnosing and managing sleep apnea in certain
      populations.

PMID- 24121752
TI  - Bacteria detected after instrumentation surgery for pyogenic vertebral
      osteomyelitis in a canine model.
AB  - OBJECTIVE: This study was designed to identify the presence, type and origin of
      bacteria adjacent to the metal implant in the infected region in a canine model
      of pyogenic vertebral osteomyelitis treated with single-stage anterior autogenous
      bone grafting and instrumentation. METHODS: Dogs with pyogenic spondylodiscitis
      underwent one-stage debridement, autogenous bone grafting and titanium plate
      instrumentation and perioperative antibiotic therapy. The implants and adjacent
      vertebral bones were removed surgically at various postoperative time points (4,
      8, 12 and 24 weeks) for bacteria detection. Bacteria were detected from retrieved
      spinal implants as well as surrounding bones by culture and/or pyrosequencing
      methods in 17 (85%) of all 20 animals. The positive rate for bacteria presence
      was 45% by culture and 80% by pyrosequencing method. RESULTS: Radiological or
      macroscopic examination showed no signs for infection recurrence in any animal
      regardless of bacteria presence at the surgical site. However, organism identical
      with the causative bacterium for spinal infection was found in only two of nine
      culture-positive animals. CONCLUSION: Within the confines of the study, the use
      of metallic implants in an infected area did not lead to a clinically relevant
      infection although bacteria may exist at the surgical site. The use of metallic
      implants in an infected area of the spine is safe. The metallic implants may not
      be the "culprit" for the persistence or recurrence of infection.

PMID- 24121753
TI  - Long-term follow-up of children in the HIVNET 012 perinatal HIV prevention trial:
      five-year growth and survival.
AB  - OBJECTIVES: To describe 5-year growth, survival, and long-term safety among
      children exposed to nevirapine or zidovudine in an African perinatal prevention
      trial, HIVNET 012. METHODS: All study children who were alive at the age 18
      months were eligible for an extended follow-up study. Children whose families
      consented were enrolled and evaluated every 6 months from 24 to 60 months. At
      each visit, history, physical examination, and growth measures were taken. From
      these measurements, Z scores based on World Health Organization (WHO) standards
      were computed. Serious adverse event data were collected. Data from the initial
      and extended follow-up cohorts were included in the analysis. RESULTS: Five
      hundred twenty-eight study children were alive at the age 18 months, and 491 (426
      HIV uninfected and 65 infected) were enrolled into the follow-up study. Both
      exposed but uninfected children and HIV-infected children were substantially
      below WHO growth standards for weight and height. Head circumference Z scores for
      uninfected children were comparable with WHO norms. Five-year survival rates were
      93% for uninfected children versus 43% for infected children. Long-term safety
      and growth outcomes in the 2 study arms were similar. CONCLUSIONS: Both infected
      and uninfected children in the 5-year HIVNET 012 follow-up showed poor height and
      weight growth outcomes, underscoring the need for early nutritional interventions
      to improve long-term growth of all infants born to HIV-infected women in resource
      limited settings. Similarly, the low 5-year survival among HIV-infected children
      support the importance of early initiation of antiretroviral therapy. Both
      peripartum nevirapine and zidovudine were safe.

PMID- 24121754
TI  - High risk of obesity and weight gain for HIV-infected uninsured minorities.
AB  - BACKGROUND: Obesity and HIV disproportionately affect minorities and have
      significant health risks, but few studies have examined disparities in weight
      change in HIV-seropositive (HIV+) cohorts. OBJECTIVE: To determine racial and
      health insurance disparities in significant weight gain in a predominately
      Hispanic HIV+ cohort. METHODS: Our observational cohort study of 1214
      nonunderweight HIV+ adults from 2007 to 2010 had significant weight gain [>=3%
      annual body mass index (BMI) increase] as the primary outcome. The secondary
      outcome was continuous BMI over time. A 4-level race-ethnicity/insurance
      predictor reflected the interaction between race-ethnicity and insurance: insured
      white (non-Hispanic), uninsured white, insured minority (Hispanic or black), or
      uninsured minority. Logistic and mixed-effects models adjusted for baseline BMI,
      age, gender, household income, HIV transmission category, antiretroviral therapy
      type, CD4 count, plasma HIV-1 RNA, observation months, and visit frequency.
      RESULTS: The cohort was 63% Hispanic and 14% black; 13.3% were insured white,
      10.0% uninsured white, 40.9% insured minority, and 35.7% uninsured minority. At
      baseline, 37.5% were overweight, 22.1% obese. Median observation was 3.25 years.
      Twenty-four percent of the cohort had significant weight gain, which was more
      likely for uninsured minority patients than insured whites [adjusted odds ratio =
      2.85, 95% confidence intervals (CIs): 1.66 to 4.90]. The rate of BMI increase in
      mixed-effects models was greatest for uninsured minorities. Of 455 overweight at
      baseline, 29% were projected to become obese in 4 years. CONCLUSIONS AND
      RELEVANCE: In this majority Hispanic HIV+ cohort, 60% were overweight or obese at
      baseline, and uninsured minority patients gained weight more rapidly. These data
      should prompt greater attention by HIV providers for prevention of obesity.

PMID- 24121756
TI  - Antiviral activity, pharmacokinetics, and safety of the HIV-1 protease inhibitor
      TMC310911, coadministered with ritonavir, in treatment-naive HIV-1-infected
      patients.
AB  - OBJECTIVES: TMC310911 is a novel HIV type-1 (HIV-1) protease inhibitor with broad
      in vitro antiviral activity. In this phase 2a, open-label randomized study, the
      antiviral activity, pharmacokinetics, and safety and tolerability of ritonavir
      boosted TMC310911 was assessed. METHODS: In this study, treatment-naive HIV-1
      patients (aged 18-60 years) received 1 of the 4 dosing regimens of TMC310911: 150
      mg twice-daily (bid) (n = 8), 300 mg bid (n = 8), 75 mg bid (n = 9), or 300 mg
      once-daily (qd) (n = 8), for 14 days, all coadministered with 100 mg of
      ritonavir, as only antiretroviral therapy. RESULTS: The mean change from baseline
      in HIV-1 RNA (log10 copies per milliliter; primary efficacy endpoint) was -1.30
      (75 mg bid), -1.14 (150 mg bid), -1.07 (300 mg bid), and -1.06 (300 mg qd) on day
      8 and -1.53 (75 mg bid), -1.79 (150 mg bid), -1.69 (300 mg bid), and -1.55 (300
      mg qd) on day 15. At steady state (day 14), the mean maximum plasma concentration
      and mean area under the plasma concentration-time curve from 0 to 12 hours tended
      to increase dose proportionally for bid doses; TMC310911 daily exposures for the
      300 mg qd treatment and 150 mg bid treatment were comparable. The most common (>=
      10%) treatment-emergent adverse events were fatigue (27.3%) and nausea (12.1%);
      no deaths or serious treatment-emergent adverse events were reported in this
      study. CONCLUSIONS: Combination treatment with TMC310911 and ritonavir showed
      potent antiviral activity (>1.5 log10 copies/mL decrease in plasma HIV-1 RNA) at
      all evaluated doses, and treatment was generally safe and well tolerated.

PMID- 24121755
TI  - Associations of inflammatory markers with AIDS and non-AIDS clinical events after
      initiation of antiretroviral therapy: AIDS clinical trials group A5224s, a
      substudy of ACTG A5202.
AB  - BACKGROUND: The association of inflammatory biomarkers with clinical events after
      antiretroviral therapy initiation is unclear. METHODS: A5202 randomized 1857
      treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/emtricitabine
      with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory
      biomarkers on subjects with available plasma from baseline and week 24 or 96. An
      exploratory analysis of the association of high-sensitivity C-reactive protein,
      interleukin-6 (IL-6), soluble receptors of tumor necrosis factor alpha (sTNF)-RI,
      sTNF-RII, TNF-alpha, soluble vascular cellular adhesion molecules (sVCAM-1), and
      soluble intercellular adhesion molecules (sICAM-1) with times to AIDS and to non
      AIDS events used Cox proportional hazards models. RESULTS: Analysis included 244
      subjects; 85% men and 48% white non-Hispanic with median age 39 years, HIV-1 RNA
      of 4.6 log10 copies per milliliter, and CD4 of 240 cells per microliter. Overall,
      13 AIDS events (9 opportunistic infections, 3 AIDS-cancers, and 1 recurrent
      bacterial pneumonia) and 18 non-AIDS events (6 diabetes, 4 cancers, 3
      cardiovascular, and 5 pneumonias) occurred. Higher baseline IL-6, sTNF-RI, sTNF
      RII, and sICAM-1 were significantly associated with increased risk of AIDS
      defining events. Adjustment for baseline HIV-1 RNA did not change results,
      whereas adjusting for baseline CD4 count left only sTNF-RI and sICAM-1
      significantly associated with increased risk. Time-updated values of IL-6, sTNFR
      I and II, and sICAM-1 were also associated with an increased risk. For non-AIDS
      events, only higher baseline high-sensitivity C-reactive protein was
      significantly associated with increased risk, whereas higher IL-6 was marginally
      associated with higher risk. Analyses of time-updated biomarker values showed
      tumor necrosis factor alpha to be significantly associated with increased risk,
      even after adjustment for antiretroviral therapy, and CD4 count or HIV-1 RNA.
      CONCLUSIONS: Higher levels of several inflammatory biomarkers were independently
      associated with increased risk of AIDS and non-AIDS events.

PMID- 24121757
TI  - Safety and pharmacokinetics of the HIV-1 protease inhibitor TMC310911
      coadministered with ritonavir in healthy participants: results from 2 phase 1
      studies.
AB  - OBJECTIVES: To evaluate safety, tolerability, and pharmacokinetics of TMC310911,
      a novel human immunodeficiency virus type-1 protease inhibitor. METHODS: Healthy
      participants aged 18-55 years with body mass index 18-30 kg/m were enrolled in 2
      phase 1 studies. In the first-in-human, single-dose study, 18 participants
      received placebo or TMC310911 (75-2000 mg) in the double-blind phase and 8
      participants received 300 or 600 mg of TMC310911 [administered alone or with 100
      mg ritonavir twice daily (bid)] in the subsequent open-label phase. The multiple
      dose double-blind study included 5 successive treatment sessions wherein healthy
      participants received placebo or TMC310911 [300 mg bid, 600 mg once daily or 150
      mg bid (plus 100 mg ritonavir bid), 900 mg bid (alone) or 300 mg bid (plus
      ritonavir 50 mg bid)]; in all sessions, TMC310911 and ritonavir were administered
      for 6 and 9 days, respectively. RESULTS: In the single-dose study, no dose
      limiting toxicity was observed up to 2000 mg of TMC310911. Systemic exposure to
      TMC310911 generally increased in a dose-proportional manner after the single- or
      multiple-dose administrations. Coadministration of ritonavir increased the
      systemic exposure to TMC310911. The mean Cmax and area under plasma concentration
      time curve values (single-dose: 1200 mg TMC310911) were higher under fasted
      conditions than in fed condition. In both studies, most treatment-emergent
      adverse events were related to gastrointestinal system. CONCLUSIONS: TMC310911
      exhibited a linear pharmacokinetic profile after the single- (up to 2000 mg) and
      multiple-dose (up to 900 mg) administrations; ritonavir improved the
      pharmacokinetic profile of TMC310911. TMC310911 was generally safe and tolerable
      when administered with or without ritonavir.

PMID- 24121758
TI  - Discordance between peripheral and colonic markers of inflammation during
      suppressive ART.
AB  - OBJECTIVE: Persistent systemic inflammation is associated with the inability of
      some HIV-infected patients to normalize circulating CD4 T-cell levels after years
      of suppressive antiretroviral therapy. In this study, we sought to understand
      whether such systemic inflammation is also associated with detectable signs of
      inflammation in biopsies from the rectosigmoid colon. DESIGN: Immunologic and
      virological parameters were studied in the peripheral blood and in rectosigmoid
      colon biopsies from individuals with viral suppression for at least 2 years and
      with peripheral CD4 T-cell levels of <350 cells per cubic millimeter (immunologic
      nonresponders, n = 18) or >500 cells per cubic millimeter (immunologic
      responders, n = 16). METHODS: Peripheral blood and rectosigmoid colon biopsies
      were analyzed by flow cytometry, enzyme-linked immunosorbent assay, and
      quantitative polymerase chain reaction. RESULTS: Nonresponders had elevated T
      cell activation and inflammatory cytokines in the circulation, but inflammatory
      gene expression in colon biopsies was not different as compared with responders,
      and there was little relationship between blood and colon markers of
      inflammation. Blood inflammatory markers were positively associated with soluble
      CD14 levels indicative of monocyte activation. CONCLUSIONS: These findings
      demonstrate that, in the context of treated HIV disease, it is easier to detect
      parameters of inflammation (including blood monocyte activation) in the
      peripheral blood than in isolated rectosigmoid colon biopsies. Accordingly,
      interventions to block such inflammation in this population might be most
      conveniently and accurately assessed in blood.

PMID- 24121759
TI  - A clinical prediction score for targeted creatinine testing before initiating
      tenofovir-based antiretroviral treatment in Cambodia.

PMID- 24121761
TI  - Jurisdiction level differences in HIV diagnosis, retention in care, and viral
      suppression in the United States.
AB  - Using data from the National HIV Surveillance System, we determined the number of
      persons diagnosed with HIV and the percentages of persons linked to care,
      retained in care, and virally suppressed across 19 jurisdictions with complete
      reporting of CD4 and viral load test results. Reports from these jurisdictions
      represent 37% of persons diagnosed with HIV infection in the United States in
      2011. Although 80% of persons diagnosed in 2011 were linked to HIV medical care
      within 3 months of diagnosis, half of all persons living with HIV in the 19
      jurisdictions were not receiving ongoing care in 2010. In addition, 43% of
      persons living with HIV by year-end 2009 and alive at year-end 2010 did not have
      a suppressed viral load, with substantial variability across the 19
      jurisdictions. These data highlight the need for improved outcomes along each
      step of the HIV continuum of care.

PMID- 24121760
TI  - Trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary
      changes in pneumocystis-colonized nonhuman primates with SHIV infection.
AB  - BACKGROUND: Despite antiretroviral therapy and trimethoprim-sulfamethoxazole (TMP
      SMX) prophylaxis, Pneumocystis pneumonia remains an important serious
      opportunistic infection in HIV-infected persons. Pneumocystis (Pc) colonization
      in HIV-infected individuals and in HIV-uninfected smokers is associated with
      chronic obstructive pulmonary disease (COPD). We previously developed a nonhuman
      primate model of HIV infection and Pc colonization and demonstrated that Pc
      colonization correlated with COPD development. In the present study, we examined
      kinetics of COPD development in non-human primate and tested the effect of Pc
      burden reduction on pulmonary function by TMP-SMX treatment. METHODS: Cynomolgus
      macaques (n = 16) were infected with simian/human immunodeficiency virus
      (SHIV89.6P), and natural Pc colonization was examined by nested polymerase chain
      reaction of serial bronchoalveolar lavage fluid and anti-Pc serology. RESULTS:
      Eleven of 16 monkeys became Pc colonized by 16 weeks post simian-human
      immunodeficiency virus (SHIV) infection. Pc colonization of SHIV-infected monkeys
      led to progressive declines in pulmonary function as early as 4 weeks after Pc
      detection. SHIV-infected and Pc-negative monkeys maintained normal lung function.
      At 25 weeks post-SHIV infection, TMP-SMX treatment was initiated in 7 Pc-positive
      (Pc+) (TMP: 20 mg/kg and SMX: 100 mg/kg, daily for 48 weeks) and 5 Pc-negative
      (Pc-) monkeys. Four SHIV+/Pc+ remained untreated for the duration of the
      experiment. Detection frequency of Pc in serial bronchoalveolar lavage fluid (P <
      0.001), as well as plasma Pc antibody titers (P = 0.02) were significantly
      reduced in TMP-SMX-treated macaques compared with untreated. CONCLUSIONS:
      Reduction of Pc colonization by TMP-SMX treatment did not improve pulmonary
      function, supporting the concept that Pc colonization results in early, permanent
      obstructive changes in the lungs of immunosuppressed macaques.

PMID- 24121762
TI  - A European Renal Best Practice (ERBP) position statement on the Kidney Disease
      Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney
      Injury: part 2: renal replacement therapy.
AB  - This paper provides an endorsement of the KDIGO guideline on acute kidney injury;
      more specifically, on the part that concerns renal replacement therapy. New
      evidence that has emerged since the publication of the KDIGO guideline was taken
      into account, and the guideline is commented on from a European perspective.
      Advice is given on when to start and stop renal replacement therapy in acute
      kidney injury; which modalities should be preferentially be applied, and in which
      conditions; how to gain access to circulation; how to measure adequacy; and which
      dose can be recommended. 

PMID- 24121763
TI  - Rituximab for minimal change disease in adults: long-term follow-up.
AB  - BACKGROUND: Minimal change nephropathy or disease (MCD) accounts for 10-15% of
      cases of the nephrotic syndrome in adults with frequent relapses occurring in up
      to 25% of cases. The drug of choice is glucocorticoids (GCs), but GC-dependence
      is seen in 25-30%. Treatment with rituximab has been found to be effective in
      relapsing and GC-dependent cases, but little data are available regarding long
      term outcome in adults. PATIENTS: We present nine female and seven male patients,
      ranging from 19 to 73 years of age with multirelapsing, GC-dependent or GC
      resistant disease with a kidney biopsy consistent with MCD. Twelve patients were
      steroid-dependent with a lowest daily GC dose between 5 and 20 mg/day. TREATMENT
      AND OUTCOMES: Rituximab with a total dose 1000-2800 mg divided in two to four
      doses was given together with GC achieving B-cell depletion before the second
      dose. No major side-effects occurred. Thirteen of the patients responded with
      complete remission enabling discontinuation or tapering of GC significantly below
      levels, where relapses had occurred in the past (P < 0.001). Two patients reached
      partial remission and one had no response to therapy. Follow-up was 12-70 months
      (median 44). Eight patients have remained in remission, whereas relapses occurred
      in seven patients after 9-28 months with repeated rituximab treatment in four of
      these. CONCLUSIONS: Our study reinforces the role of rituximab as a GC-sparing
      agent in the challenging GC-dependent and multirelapsing MCD patients. In this
      emerging therapeutic field randomized studies with extended follow-up will add
      important information regarding optimal treatment, relapse and safety.

PMID- 24121764
TI  - The effect of water on the microstructure and properties of
      benzene/[bmim][AOT]/[bmim][BF4] microemulsions.
AB  - In the present contribution, results concerning the role of small amounts of
      water in the 1-butyl-3-methylimidazolium bis 2-ethylhexyl sulfosuccinate
      ([bmim][AOT]) based 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4])
      in-benzene reverse microemulsions are emphasized. The microemulsion aggregates
      have demonstrated features in common with traditional aqueous systems, such as a
      normal microemulsion droplet size and decreased stability due to the addition of
      a polar component. Dynamic light scattering (DLS) showed that the size change of
      microemulsion with added water depends on the loaded [bmim][BF4] content in the
      microemulsion: when the [bmim][BF4] content is low, the microemulsion diameter
      first decreases and then increases, while the size remains about the same for
      microemulsions with a moderate [bmim][BF4] loading and a successive increase in
      size was found for high-loaded [bmim][BF4] microemulsions. (1)H NMR along with
      two-dimensional rotating frame nuclear Overhauser effect (NOE) experiments
      (ROESY) revealed that water molecules formed wide interactions with both 1-butyl
      3-methylimidazolium ([bmim]) and bis 2-ethylhexyl sulfosuccinate ([AOT]), leading
      to a decrease in the headgroup area of [bmim][AOT], i.e. alpha value, which will
      decrease the microemulsion size. On the other hand, addition of water can
      simultaneously swell the microemulsions, causing an increase in the diameter. It
      is also deduced that the Coulomb forces between the [AOT] and [bmim] should be
      one of the main driving forces for the formation of [bmim][BF4]-in-benzene
      microemulsions. 

PMID- 24121766
TI  - Prenatal diagnosis of metatropic dysplasia: beware of the pseudo-bowing sign.
AB  - Metatropic dysplasia is a very rare form of osteochondrodysplasia with only one
      case of prenatal diagnosis described in the literature. It is characterized by
      marked shortening of the long bones with severe platyspondyly and dumbbell-shape
      metaphyses. We report a case of metatropic dysplasia that was diagnosed
      prenatally and describe the findings on US and CT. The pregnancy was terminated
      and the post-mortem radiographs are shown. The woman had been referred for short
      and bowed long bones. Severe metaphyseal enlargement was a misleading finding
      because it had been misinterpreted as limb bowing. Thus when abnormal curvature
      of the long bones is observed at prenatal US, attention should be drawn not only
      to the diaphyses but also to the metaphyses because severe metaphyseal
      enlargement might be responsible for pseudo-bowing.

PMID- 24121765
TI  - Dual depolarization responses generated within the same  lateral septal neurons
      by TRPC4-containing channels.
AB  - In the central nervous system, canonical transient receptor potential (TRPC)
      channels have been implicated in mediating neuronal excitation induced by
      stimulating metabotropic receptors, including group 1 metabotropic glutamate
      receptors (mGluRs). Lateral septal (LS) neurons express high levels of TRPC4 and
      group I mGluRs. However, to what extent native TRPC4-containing channels (TRPC4
      cc) are activated as well as the impact of different levels of TRPC4-cc
      activation on neuronal excitability remain elusive. Here, we report that
      stimulating LS neurons with group I mGluR agonist, (S)-3,5-DHPG, causes either an
      immediate increase in firing rate or an initial burst followed by a pause of
      firing, which can be correlated with below-threshold-depolarization (BTD) or
      above-threshold-plateau-depolarization (ATPD), respectively, in whole-cell
      recordings. The early phase of BTD and the entire ATPD are completely absent in
      neurons from TRPC4-/- mice. Moreover, in the same LS neurons, BTD can be
      converted to ATPD at more depolarized potentials or with a brief current
      injection, suggesting that BTD and ATPD may represent partial and full
      activations of TRPC4-cc, respectively. We show that coincident mGluR stimulation
      and depolarization is required to evoke strong TRPC4-cc current, and Na+ and Ca2+
      influx, together with dynamic changes of intracellular Ca(2+), are essential for
      ATPD induction. Our results suggest that TRPC4-cc integrates metabotropic
      receptor stimulation with intracellular Ca(2+) signals to generate two
      interconvertible depolarization responses to affect excitability of LS neurons in
      distinct fashions.

PMID- 24121767
TI  - Dos and don'ts of intermittent self-catheterisation.

PMID- 24121768
TI  - A survey of short- and long-term pre-lubricated intermittent catheters.
AB  - The prospect of having to undertake clean intermittent self-catheterisation
      (CISC) for a short time, or for the rest of a patient's life, can be very
      daunting. It has an impact on their social, sexual, work and family life. Despite
      the challenges of the practical performance of the procedure, CISC has many
      advantages and is a means of reducing the subsequent problems and cost
      implications associated with long-term indwelling catheter use. There are many
      different products available on prescription for patients performing CISC and it
      can be a challenge to choose the right one. This article discusses the impact
      CISC has on the individual and focuses on a regional survey conducted in a
      district in the UK of nearly 100 patients who agreed to complete a confidential
      questionnaire about their experiences using a pre-lubricated CISC catheter
      (Actreen(r)). It also discusses the challenges facing nurses with patients
      practising CISC and offers advice to help patients come to terms with this
      procedure and its effect on their daily life. 

PMID- 24121769
TI  - Intermittent self-catheterisation: managing bladder dysfunction.

PMID- 24121770
TI  - Digital engagement in nursing: a urology nurse's journey.
AB  - The use of technology is transforming society-underpinning communication,
      information gathering and collaboration. Indeed, 2013 may prove to be the tipping
      point for healthcare delivery. No longer are policies and guidance documents
      being produced solely on the basis of cautions and negatives. We are entering a
      new era. Documents are now being produced that are constructive, focusing equally
      on positives and collaboration. Digital engagement within nursing and healthcare
      communities can be a tremendously positive experience; with the help of online
      resources, we can be part of the tipping point. From micro blogging to content
      communities, from collaborative projects to social networking, Web2.0 technology
      is providing 21st-century practitioners with opportunities we have not yet fully
      realised the potential of-for ourselves, our patients or our institutions. In
      this article, I share my personal journey, aiming to show my fellow healthcare
      practitioners how these technologies might be used to inform and improve nursing
      practice, within urology and beyond. 

PMID- 24121771
TI  - Falling nursing numbers are impacting patient care.

PMID- 24121772
TI  - Treatment of ketamine-associated cystitis with chondroitin sulphate.
AB  - Chronic cystitis associated with ketamine use is a growing problem among a young
      patient population who use the drug recreationally. Patients may present with
      symptoms such as urinary frequency, dysuria, urgency and haematuria in accident
      and emergency departments, GP surgeries, urology outpatient departments, drug
      rehabilitation or substance misuse units, genitourinary medicine clinics or
      continence services. Nurses in these areas therefore need to be aware of the
      symptoms associated with ketamine-associated bladder damage and be prepared to
      ask patients about recreational drug use and inform them of possible treatments.
      This case report illustrates one patient's successful response to treatment with
      chondroitin sulphate 0.2% (Gepan) over a 1-year period. 

PMID- 24121773
TI  - The evolutionary genetics of the genes underlying phenotypic associations for
      loblolly pine (Pinus taeda, Pinaceae).
AB  - A primary goal of evolutionary genetics is to discover and explain the genetic
      basis of fitness-related traits and how this genetic basis evolves within natural
      populations. Unprecedented technological advances have fueled the discovery of
      genetic variants associated with ecologically relevant phenotypes in many
      different life forms, as well as the ability to scan genomes for deviations from
      selectively neutral models of evolution. Theoretically, the degree of overlap
      between lists of genomic regions identified using each approach is related to the
      genetic architecture of fitness-related traits and the strength and type of
      natural selection molding variation at these traits within natural populations.
      Here we address for the first time in a plant the degree of overlap between these
      lists, using patterns of nucleotide diversity and divergence for >7000 unique
      amplicons described from the extensive expressed sequence tag libraries generated
      for loblolly pine (Pinus taeda L.) in combination with the >1000 published
      genetic associations. We show that loci associated with phenotypic traits are
      distinct with regard to neutral expectations. Phenotypes measured at the whole
      plant level (e.g., disease resistance) exhibit an approximately twofold increase
      in the proportion of adaptive nonsynonymous substitutions over the genome-wide
      average. As expected for polygenic traits, these signals were apparent only when
      loci were considered at the level of functional sets. The ramifications of this
      result are discussed in light of the continued efforts to dissect the genetic
      basis of quantitative traits. 

PMID- 24121774
TI  - Genetically engineered transvestites reveal novel mating genes in budding yeast.
AB  - Haploid budding yeast has two mating types, defined by the alleles of the MAT
      locus, MATa and MATalpha. Two haploid cells of opposite mating types mate by
      signaling to each other using reciprocal pheromones and receptors, polarizing and
      growing toward each other, and eventually fusing to form a single diploid cell.
      The pheromones and receptors are necessary and sufficient to define a mating
      type, but other mating-type-specific proteins make mating more efficient. We
      examined the role of these proteins by genetically engineering "transvestite"
      cells that swap the pheromone, pheromone receptor, and pheromone processing
      factors of one mating type for another. These cells mate with each other, but
      their mating is inefficient. By characterizing their mating defects and examining
      their transcriptomes, we found Afb1 (a-factor barrier), a novel MATalpha-specific
      protein that interferes with a-factor, the pheromone secreted by MATa cells.
      Strong pheromone secretion is essential for efficient mating, and the weak mating
      of transvestites can be improved by boosting their pheromone production.
      Synthetic biology can characterize the factors that control efficiency in
      biological processes. In yeast, selection for increased mating efficiency is
      likely to have continually boosted pheromone levels and the ability to
      discriminate between partners who make more and less pheromone. This
      discrimination comes at a cost: weak mating in situations where all potential
      partners make less pheromone. 

PMID- 24121775
TI  - On the additive and dominant variance and covariance of individuals within the
      genomic selection scope.
AB  - Genomic evaluation models can fit additive and dominant SNP effects. Under
      quantitative genetics theory, additive or "breeding" values of individuals are
      generated by substitution effects, which involve both "biological" additive and
      dominant effects of the markers. Dominance deviations include only a portion of
      the biological dominant effects of the markers. Additive variance includes
      variation due to the additive and dominant effects of the markers. We describe a
      matrix of dominant genomic relationships across individuals, D, which is similar
      to the G matrix used in genomic best linear unbiased prediction. This matrix can
      be used in a mixed-model context for genomic evaluations or to estimate dominant
      and additive variances in the population. From the "genotypic" value of
      individuals, an alternative parameterization defines additive and dominance as
      the parts attributable to the additive and dominant effect of the markers. This
      approach underestimates the additive genetic variance and overestimates the
      dominance variance. Transforming the variances from one model into the other is
      trivial if the distribution of allelic frequencies is known. We illustrate these
      results with mouse data (four traits, 1884 mice, and 10,946 markers) and
      simulated data (2100 individuals and 10,000 markers). Variance components were
      estimated correctly in the model, considering breeding values and dominance
      deviations. For the model considering genotypic values, the inclusion of dominant
      effects biased the estimate of additive variance. Genomic models were more
      accurate for the estimation of variance components than their pedigree-based
      counterparts. 

PMID- 24121776
TI  - Allelic diversity and its implications for the rate of adaptation.
AB  - Genetic variation is usually estimated empirically from statistics based on
      population gene frequencies, but alternative statistics based on allelic
      diversity (number of allelic types) can provide complementary information. There
      is a lack of knowledge, however, on the evolutionary implications attached to
      allelic-diversity measures, particularly in structured populations. In this
      article we simulated multiple scenarios of single and structured populations in
      which a quantitative trait subject to stabilizing selection is adapted to
      different fitness optima. By forcing a global change in the optima we evaluated
      which diversity variables are more strongly correlated with both short- and long
      term adaptation to the new optima. We found that quantitative genetic variance
      components for the trait and gene-frequency-diversity measures are generally more
      strongly correlated with short-term response to selection, whereas allelic
      diversity measures are more correlated with long-term and total response to
      selection. Thus, allelic-diversity variables are better predictors of long-term
      adaptation than gene-frequency variables. This observation is also extended to
      unlinked neutral markers as a result of the information they convey on the
      demographic population history. Diffusion approximations for the allelic
      diversity measures in a finite island model under the infinite-allele neutral
      mutation model are also provided. 

PMID- 24121777
TI  - Treatment and outcome of middle ear cancer.
AB  - This study addressed the clinical characteristics, treatment, and outcome of
      middle ear cancer. A series of 33 patients with middle ear cancer were analyzed
      with survival, the primary outcome. Altogether, 25 patients underwent surgery
      with adjuvant radiotherapy, seven patients had surgery alone, and one patient had
      only radiotherapy. The patients were staged according to the Stell staging
      system. Among patients with T1/T2 cancers, five underwent lateral temporal bone
      resection (LTBR) and three underwent subtotal temporal bone resection (STBR).
      Among those with T3/Tx cancers, 11 underwent LTBR, and 13 had STBR. Of the total
      33 patients, 18 died of their disease during follow-up. The overall 5-year
      survival rate was 37.4 %. The 5-year survival rates for patients with T1/T2
      disease and T3/Tx disease were 85.7 and 22.0 %, respectively. There was a
      statistically significant difference in 5-year survival rates between the two
      groups using the log-rank test (P < 0.05). The 5-year survival rates after LTBR
      and STBR for the T3/Tx group were 15.2 and 30.8 % (P > 0.05), respectively, and
      those for the T1/T2 group were 100 and 66.7 % (P > 0.05), respectively. The 5
      year survival rates for patients who underwent preoperative or postoperative
      radiotherapy were 38.9 and 40.4 %, respectively (P > 0.05). En bloc resection is
      favored in an effort to produce negative surgical margins for middle ear cancer.
      Adjunctive radiotherapy is used for advanced lesions.

PMID- 24121778
TI  - The occurrence of molds in patients with chronic sinusitis.
AB  - Chronic rhinosinusitis (CRS) is a common inflammatory condition of nasal and
      paranasal sinus mucosa. Although pathogenic bacteria were postulated as main
      etiological factor responsible for most cases of CRS, the involvement of molds
      was recently proved in some cases. The aim of the study was to conduct
      mycological analysis of material obtained from patients operated on due to
      chronic sinusitis. The study included 107 patients, 45 women and 62 men. During
      the surgery, a fragment of mucosa from the region of the ethmoid bulla was
      obtained as microbiological characteristics of this material closely resemble
      those of sinus mucosa. In addition, maxillary sinus lavage was obtained. The
      control group comprised patients without chronic sinusitis. The dithiothreitol
      solution method was used for the lavage examination. The tissue material (mucosal
      fragment from the region of the ethmoid bulla) was incubated in 2% liquid
      Sabouraud medium for 24 h. The material was inoculated onto culture media. The
      presence of molds was detected in 67% of examined samples. Overall, 41 species
      belonging to 12 genera were isolated. The most frequently detected genera
      included Penicillium spp. (46%) and Aspergillus spp. (16%). In addition,
      Cladosporium spp. (11%), Fusarium spp. (7%), Acremonium spp. (4%), Eurotium spp.
      (4%), Alternaria spp. (2%), Chaetomium spp. (1%), Geotrichum spp. (1%),
      Verticillium spp. (1%), Rhizopus spp. (1%), and some unidentified colonies (5%)
      were isolated. Penicillium crustosum, Penicillium citrinum, Aspergillus niger,
      Cladosporium cladosporioides, and Fusarium verticillioides were the most
      prevalent species.

PMID- 24121779
TI  - Letter to the editor of European Archives of Otorhinolaryngology.

PMID- 24121781
TI  - Clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients
      with recurrent respiratory papillomatosis.
AB  - The aim of the study was to assess the clinical efficiency of quadrivalent HPV
      (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis
      (RRP). This was a prospective study of patients with RRP treated from January
      2009 to July 2012 at the Ear, Nose and Throat Department of the Emergency County
      Hospital of Cluj-Napoca, Romania. Demographic characteristics, onset of RRP, HPV
      typing, use and number of cidofovir injections, number of surgeries for RRP per
      year, and use of human papillomavirus vaccine (types 6, 11, 16, 18) (recombinant,
      adsorbed)/Silgard(r) were considered from all the patients included in the study.
      Charts were reviewed for follow-up after diagnosis, after cidofovir, and after
      Silgard; all the statistical tests were applied at a significance level of 5%.
      The recurrences were observed within 27.53 +/- 11.24 days after intralesional
      cidofovir injection. Thirteen patients with recurrence after cidofovir agreed and
      received Silgard(r) vaccine. 85% [54.44-99.41] of patients had no recurrences
      during 1-year follow-up. The recurrence of papillomas was observed in two
      patients (15%, 95% CI [0.59-45.56]), one with adult-onset RRP and one with
      juvenile-onset RRP. Both recurrences appeared after the first Silgard dose; one
      month after the third vaccine dose each patient underwent a new surgery for
      remaining papillomas with no recurrences at 1-year follow-up visit. Silgard(r)
      vaccination had a good effect and proved to be efficient in the treatment of our
      patients with RRR without appearance of recurrence in 85% of the patients during
      1-year follow-up.

PMID- 24121782
TI  - Enhanced expressions of lysozyme, SLPI and glycoprotein 340 in biofilm-associated
      chronic rhinosinusitis.
AB  - Lysozyme, secretory leukocyte proteinase inhibitor (SLPI) and glycoprotein 340
      (gp340) are important effectors of the innate immune system in sinonasal mucosa.
      Bacterial biofilms (BBF) are highly organized bacterial communities resistant to
      host defense systems. The aim of this study was to investigate the expression of
      lysozyme, SLPI and gp340 in sinus mucosa from chronic rhinosinusitis (CRS)
      patients with different BBF status. In this prospective cohort study, 63 CRS
      patients undergoing endoscopic sinus surgery and 20 controls were enrolled and
      their mucosal samples from ethmoid sinus were obtained. Biofilms were examined by
      confocal scanning laser microscopy (CSLM), and the expressions of lysozyme, SLPI
      and gp340 in mRNA and protein levels were detected using reverse transcription
      polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot assay,
      respectively. As a result, 35/63 (55.6%) of the patients were BBF positive in the
      CRS group and none in controls. Both mRNA and protein levels of lysozyme, SLPI
      and gp340 in patients with CRS were significantly higher than those in controls.
      When sub-classified according to BBF status, the CRS patients with BBF revealed
      the significantly enhanced mRNA and protein levels of lysozyme, SLPI and gp340.
      In conclusion, our study demonstrates that lysozyme, SLPI and gp340 are
      constitutively expressed in sinus mucosa and their up-regulated expressions on
      both the mRNA and protein levels are associated with BBF in CRS patients. These
      findings may offer an insight into the interaction between BBF and the innate
      immune system.

PMID- 24121780
TI  - Endolymphatic hydrops in patients with vestibular migraine and auditory symptoms.
AB  - Vertigo patients exhibiting features of vestibular migraine (VM) and Meniere's
      disease (MD) present a difficult diagnostic challenge to the clinician, and the
      two entities are likely to overlap. The aim of the present study was to
      investigate the occurrence of endolymphatic hydrops in patients with VM and
      auditory symptoms. This was an observatory diagnostic study. At an academic
      interdisciplinary dizziness centre, nineteen consecutive patients with definite
      or probable VM and auditory symptoms were examined by locally enhanced inner ear
      MR imaging. MR images were evaluated for the presence of endolymphatic hydrops.
      Of the 19 included patients, four patients (21 %) demonstrated evidence of
      cochlear and vestibular endolymphatic hydrops on locally enhanced inner ear MR
      imaging (three with "definite VM", one with "probable VM"). Locally enhanced
      inner ear MR imaging may be useful in the diagnostic evaluation of patients with
      VM and auditory symptoms, as some of these patients have signs of endolymphatic
      hydrops. Whether these patients suffer from MD only and are misdiagnosed as VM or
      suffer from both, VM and MD or whether endolymphatic hydrops is a consequence of
      inner ear damage due to VM are clinically relevant questions that can be
      evaluated by application of this technique.

PMID- 24121783
TI  - Retrospective analysis of the clinical course for intubation vs. unspecified
      laryngeal granulomas.
AB  - Intubation laryngeal granulomas (ILGs) are a well-known complication of
      endotracheal intubation. Cases other than ILGs can be categorized as unspecified
      laryngeal granulomas (ULGs) since their etiologies are often difficult to
      confirm. We intended to clarify clinical features of both ILGs and ULGs and that
      anticoagulant medication could cause the formation and delayed healing of ILGs in
      terms of wound-healing delay. We compared the results of our treatment of ILGs (n
      = 16) and ULGs (n = 47) treated between 1998 and 2009 to characterize these
      patients. The clinical course, treatment (medical vs. surgical), indications for
      surgical resection, treatment outcome, and use of anticoagulants for preexisting
      disease were reviewed and compared between these two groups. The resolution rate
      was significantly better in ILGs (p < .05). Five ILGs and seven ULGs were
      surgically resected. The main reason for resection was airway obstruction and the
      need for histological assessment, respectively. The use of anticoagulants was
      significantly higher in ILGs than ULGs (8/16 vs. 4/47, p < .01). The resolution
      period was significantly longer in the ILGs patients with anticoagulant
      medication compared to that in the ILGs patients without anticoagulant medication
      (152 +/- 101 days vs. 76 +/- 44 days, p < .05). ILGs may have different clinical
      course from ULGs, especially in terms of the resolution period. Moreover,
      administration of anticoagulants may deter healing of small injury due to
      intubation. Patients taking anticoagulants should be managed carefully during the
      perioperative period to prevent the occurrence of ILGs.

PMID- 24121784
TI  - Transient evoked otoacoustic emissions and vestibular evoked myogenic potentials
      in cigarette and water pipe smokers.
AB  - This study compared the amplitude of transient evoked otoacoustic emissions
      (TEOAEs) and latencies of vestibular evoked myogenic potentials (VEMPs) among non
      smokers, cigarette smokers, water pipe smokers, mixed smokers and ex-smokers. A
      total of 50 non-smokers, 28 water pipe smokers, 34 pure cigarette smokers, 28
      mixed cigarette-water pipe smokers, and 21 ex-smokers were evaluated in this
      study. Their age ranged from 20 to 40 years. All had normal hearing sensitivity
      and normal middle ear functions. TEOAEs amplitude and VEMPs were measured for all
      participants. Results of this study showed that smoking had deleterious effects
      on the hair cells in the labyrinth. Damage to the outer hair cells was evidenced
      by the reduced amplitude of the TEOAEs in smokers and ex-smokers when compared
      with control group. Harm to the saccular hair cells is detected by the increased
      latency of the VEMPs. Results also suggested that cessation of smoking could not
      change the profile of TEOAEs or VEMPs. Our results suggested that smoking could
      have irreversible hazardous effects on the labyrinthine hair cell functions.
      These effects could be attributed to the impact of nicotine on the microvascular
      dynamics.

PMID- 24121785
TI  - Videolaryngoscopy: towards a new standard method for tracheal intubation in the
      ICU?

PMID- 24121786
TI  - Fast magnetic relaxation in an octahedral dysprosium tetramethyl-aluminate
      complex.
AB  - Ab initio calculations on the octahedral dysprosium aluminate complex
      [Dy(AlMe4)3] (1) predict weak SMM properties. Dynamic magnetic susceptibility
      measurements on 1 confirm the theoretical predictions, revealing fast relaxation
      of the magnetization via quantum tunnelling.

PMID- 24121787
TI  - Highly enhanced Raman scattering of graphene using plasmonic nano-structure.
AB  - Highly enhanced Raman scattering of graphene on a plasmonic nano-structure
      platform is demonstrated. The plasmonic platform consists of silver nano
      structures in a periodic array on top of a gold mirror. The gold mirror is used
      to move the hot spot to the top surface of the silver nano-structures, where the
      graphene is located. Two different nano-structures, ring and crescent, are
      studied. The actual Raman intensity is enhanced by a factor of 890 for the G-peak
      of graphene on crescents as compared to graphene on a silicon dioxide surface.
      The highest enhancement is observed for the G-peak as compared to the 2D-peak.
      The results are quantitatively well-matched with a theoretical model using an
      overlap integral of incident electric field intensities with the corresponding
      intensities of Raman signals at the G- and 2D-peaks. The interaction of light
      with nano-structures is simulated using finite element method (FEM).

PMID- 24121788
TI  - Optimize flue gas settings to promote microalgae growth in photobioreactors via
      computer simulations.
AB  - Flue gas from power plants can promote algal cultivation and reduce greenhouse
      gas emissions(1). Microalgae not only capture solar energy more efficiently than
      plants(3), but also synthesize advanced biofuels(2-4). Generally, atmospheric CO2
      is not a sufficient source for supporting maximal algal growth(5). On the other
      hand, the high concentrations of CO2 in industrial exhaust gases have adverse
      effects on algal physiology. Consequently, both cultivation conditions (such as
      nutrients and light) and the control of the flue gas flow into the photo
      bioreactors are important to develop an efficient "flue gas to algae" system.
      Researchers have proposed different photobioreactor configurations(4,6) and
      cultivation strategies(7,8) with flue gas. Here, we present a protocol that
      demonstrates how to use models to predict the microalgal growth in response to
      flue gas settings. We perform both experimental illustration and model
      simulations to determine the favorable conditions for algal growth with flue gas.
      We develop a Monod-based model coupled with mass transfer and light intensity
      equations to simulate the microalgal growth in a homogenous photo-bioreactor. The
      model simulation compares algal growth and flue gas consumptions under different
      flue-gas settings. The model illustrates: 1) how algal growth is influenced by
      different volumetric mass transfer coefficients of CO2; 2) how we can find
      optimal CO2 concentration for algal growth via the dynamic optimization approach
      (DOA); 3) how we can design a rectangular on-off flue gas pulse to promote algal
      biomass growth and to reduce the usage of flue gas. On the experimental side, we
      present a protocol for growing Chlorella under the flue gas (generated by natural
      gas combustion). The experimental results qualitatively validate the model
      predictions that the high frequency flue gas pulses can significantly improve
      algal cultivation. 

PMID- 24121789
TI  - Frequent truncating mutations of STAG2 in bladder cancer.
AB  - Here we report the discovery of truncating mutations of the gene encoding the
      cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation,
      in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive
      urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role
      in controlling chromosome number but not the proliferation of bladder cancer
      cells. These findings identify STAG2 as one of the most commonly mutated genes in
      bladder cancer. 

PMID- 24121790
TI  - A genome-wide association study identifies new susceptibility loci for esophageal
      adenocarcinoma and Barrett's esophagus.
AB  - Esophageal adenocarcinoma is a cancer with rising incidence and poor survival.
      Most such cancers arise in a specialized intestinal metaplastic epithelium, which
      is diagnostic of Barrett's esophagus. In a genome-wide association study, we
      compared esophageal adenocarcinoma cases (n = 2,390) and individuals with
      precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases.
      For the combined case group, we identified three new associations. The first is
      at 19p13 (rs10419226: P = 3.6 * 10(-10)) in CRTC1 (encoding CREB-regulated
      transcription coactivator), whose aberrant activation has been associated with
      oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 * 10(-9)) in BARX1,
      which encodes a transcription factor important in esophageal specification. A
      third is at 3p14 (rs2687201: P = 5.5 * 10(-9)) near the transcription factor
      FOXP1, which regulates esophageal development. We also refine a previously
      reported association with Barrett's esophagus near the putative tumor suppressor
      gene FOXF1 at 16q24 and extend our findings to now include esophageal
      adenocarcinoma. 

PMID- 24121791
TI  - Recurrent inactivation of STAG2 in bladder cancer is not associated with
      aneuploidy.
AB  - Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological
      and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors
      associated with outcome and determine patient management. A discovery exome
      sequencing screen (n = 17), followed by a prevalence screen (n = 60), identified
      new genes mutated in this tumor coding for proteins involved in chromatin
      modification (MLL2, ASXL2 and BPTF), cell division (STAG2, SMC1A and SMC1B) and
      DNA repair (ATM, ERCC2 and FANCA). STAG2, a subunit of cohesin, was significantly
      and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and
      its loss was associated with improved outcome. Loss of expression was often
      observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer
      cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells
      led to reduced colony formation. Our findings indicate that STAG2 is a new UBC
      tumor suppressor acting through mechanisms that are different from its role in
      preventing aneuploidy. 

PMID- 24121793
TI  - Spino-pelvic-rhythm with forward trunk bending in normal   subjects without low
      back pain.
AB  - A strong correlation between low back pain and tight hamstrings has been
      reported. However, the effect of tight hamstrings on spinal biomechanics remains
      unclear. The purpose of the study was to investigate spino-pelvic-rhythm during
      forward bending of the trunk and to clarify the rhythm features with regard to
      hamstrings tightness. Eighteen healthy male adults with no history of low back
      pain volunteered to participate. First, we measured the finger-to-floor distance
      (FFD) in the upright position and set this parameter to 100 %. Using a spinal
      mouse, spinal alignment was measured in the following four positions: (1) upright
      posture-100 % FFD; (2) forward bending-50 % FFD; (3) forward bending-25 % FFD;
      and (4) forward bending-0 % FFD (fingers in contact with the floor). Changes of
      the angle of the thoracic and lumbar spine as well as the pelvis were calculated.
      As an indicator of tight hamstrings, we measured straight leg raising (SLR)
      angle. From positions 1-2 (phase I), the entire spino-pelvic angle moved in 104
      degrees . During this phase, the lumbar spine mainly moved. In the second phase
      (positions 2-3), it moved in 16 degrees . Interestingly, all but 2 subjects
      showed a negative angle in the thoracic motion, meaning that the thoracic spine
      extended 4 degrees  during trunk flexion, thus exhibiting paradoxical motion.
      During this phase, lumbopelvic rhythm showed 2 patterns. In 7 subjects, pelvic
      motion was greater than lumbar motion, while the remaining subjects showed the
      opposite. In subjects without tight hamstrings, 83 % showed a pelvis-dominant
      pattern. Only 7 subjects were capable of position 4. During this phase, only
      slight motion was noted in the spine, and the majority of the motion occurred in
      the pelvis. Lumbar and pelvic motion correlated negatively in all phases. SLR
      angle and pelvic motion correlated strongly during phase III, indicating dominant
      pelvic movement in flexible subjects. The lumbo-pelvic-rhythm comprises 2
      patterns-lumbar dominant and pelvis dominant. In flexible subjects, pelvis
      movement was dominant. In conclusion, improving tight hamstrings may reduce
      lumbar loading thereby reducing low back pain.

PMID- 24121794
TI  - Outcome of iatrogenic collateral ligaments injuries during total knee
      arthroplasty.
AB  - Soft tissue balance is an essential step in total knee arthroplasty by providing
      a good knee stability and an even distribution of load over the prosthesis
      components. During surgery, because of the need of having a good balance in most
      cases is necessary to do some soft tissue release in the medial compartment.
      Lateral release is far more rare and is generally needed for patients with valgus
      knees after high tibial osteotomy. Our purpose is to evaluate the complications
      that arise during soft tissue release and how to manage this unfortunate events
      for getting the best functional results for the patients. In this study, we
      analyzed 434 knee arthroplasties that were operated in our clinic in the past 8
      years by the same knee team (2005-2012). Average age was 64.8 years. Eight of
      this patients had medial collateral ligament injuries during surgery, and two had
      lateral collateral ligament rupture. Average age of patients who suffered from
      medial collateral ligaments injuries was 62.8 years and for lateral collateral
      ligaments was 72.5 years. Body mass index was 34 for both groups. We used for
      evaluation the knee society pain and functional scores, and X-rays obtained after
      the surgery with a calibrated Siemens machine. Seven patients with MCL repair
      were satisfied with after surgery (Knee Society score was 87.7, and functional
      score was 80). One complained of knee instability associated with pain and needed
      revision. In LCL group, all patients had excellent results (Knee Society score
      was 91.5, and functional score was 85). We found that repair to collateral
      ligaments injuries must be obtained during surgery, especially complete ruptures
      of the MCL. There are several approaches to collateral ligaments ruptures during
      total knee arthroplasty that will be discussed during the article.

PMID- 24121792
TI  - Whole-genome and whole-exome sequencing of bladder cancer identifies frequent
      alterations in genes involved in sister chromatid cohesion and segregation.
AB  - Bladder cancer is one of the most common cancers worldwide, with transitional
      cell carcinoma (TCC) being the predominant form. Here we report a genomic
      analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals
      with TCC. Beyond confirming recurrent mutations in genes previously identified as
      being mutated in TCC, we identified additional altered genes and pathways that
      were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and
      ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS)
      process. Furthermore, we also detected a recurrent fusion involving FGFR3 and
      TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced
      tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the
      SCCS process. Our analysis provides evidence that genetic alterations affecting
      the SCCS process may be involved in bladder tumorigenesis and identifies a new
      therapeutic possibility for bladder cancer. 

PMID- 24121795
TI  - Diagnosing joint infections: synovial fluid differential is more sensitive than
      white blood cell count.
AB  - In order to identify the predictive value of synovial fluid white blood cell
      (WBC) count and differential white blood cell count in identifying nonprosthetic
      joint infection in immunocompetent and immunosuppressed populations, we
      retrospectively reviewed 96 adult patients who underwent hip or knee aspiration
      because of symptoms suggesting a possible nonprosthetic joint infection. Medical
      history, including immunosuppressive disease or drugs, was recorded, and synovial
      fluid cell count, differential, and culture results were compared. There were 44
      patients with positive synovial cultures. Of 36 patients who had a synovial WBC
      >=50,000/mm3, 89% had positive cultures. The sensitivity to synovial WBC
      >=50,000/mm3 was 0.727 (95% CI 0.570-0.845), and specificity was 0.923 (95% CI
      0.806-0.975). There were 12 patients with a synovial WBC <50,000/mm3 that had
      positive cultures. The sensitivity of percentage polymorphonuclear cells (%PMNs)
      to predict positive cultures when the %PMNs were at least 80, 85, and 90% was
      0.932, 0.886, and 0.818, respectively. The specificity when the %PMNs was at
      least 80, 85, and 90% was 0.598, 0.577, and 0.673, respectively. Among the 29% of
      immunocompromised patients, the sensitivity to synovial WBC >=50,000/mm3 was
      0.714 (95% CI 0.420-0.904), and specificity was 1.000 (95% CI 0.732-1.000).
      Twenty-nine percent of patients with a synovial WBC <50,000/mm3 had positive
      cultures. The sensitivity of %PMNs to predict positive cultures when the %PMNs
      was at least 80, 85, and 90% was 1.000, 0.929, and 0.786, respectively. The
      specificity when the %PMNs were at least 80, 85, and 90% was 0.500, 0.643, and
      0.714, respectively. We found that the synovial WBC differential (percentage
      synovial fluid PMNs) is a more sensitive predictor for nonprosthetic adult joint
      infection than the synovial absolute WBC count. This was true in both the general
      population and the immunosuppressed population.

PMID- 24121796
TI  - Flexor tendon repair with barbed suture: an experimental study.
AB  - Various suture materials have been used for tendon repair. Barbed suture in
      particular has been demonstrated to be effective for both wound closure and
      tendon repair. Ten fresh-frozen flexor digitorum profundus tendons of pig were
      transected and repaired using the two-strand modified Kirchmayr-Kessler
      technique. The samples were divided into two groups: 4-0 barbed absorbable
      polyglyconate sutures and 4-0 monofilament absorbable polyglyconate sutures. We
      measured tensile strength and distance that the testing system pulled the tendon
      using a universal testing machine. Tensile strength at which 1 and 2 mm of
      gapping occurred was measured visually at the repair site. Tendons repaired by
      barbed sutures showed greater tensile strength than monofilament sutures forming
      still 2-mm gap. However, statistical significance was obtained only at 1-mm gap
      formation. We concluded that for tendon repair, barbed sutures were superior
      material to monofilament sutures because of their greater tensile strength,
      reducing both the initial tendon load and the risk of dehiscence.

PMID- 24121797
TI  - Z-Selective ring opening of vinyl oxetanes with dialkyl dithiophosphate
      nucleophiles.
AB  - Dialkyl dithiophosphates selectively ring open vinyl oxetanes in excellent yields
      under mild reaction conditions to form useful allylic thiophosphate products with
      high Z-selectivity. 

PMID- 24121798
TI  - Ultrathin graphitic carbon nitride nanosheets: a novel peroxidase mimetic, Fe
      doping-mediated catalytic performance enhancement and application to rapid,
      highly sensitive optical detection of glucose.
AB  - In this article, we demonstrate for the first time that ultrathin graphitic
      carbon nitride nanosheets (g-C3N4) possess peroxidase activity. Fe doping of the
      nanosheets leads to peroxidase mimetics with greatly enhanced catalytic
      performance and the mechanism involved is proposed. We further demonstrate the
      novel use of such Fe-g-C3N4 as a cheap nanosensor for simple, rapid, highly
      selective and sensitive optical detection of glucose with a pretty low detection
      limit of 0.5 MUM. 

PMID- 24121800
TI  - Low temperature reveals genetic variability against male-killing Spiroplasma in
      Drosophila melanogaster natural populations.
AB  - Spiroplasma endosymbionts are maternally inherited microorganisms which infect
      many arthropod species. In some Drosophila species, it acts as a reproductive
      manipulator, spreading in populations by killing the sons of infected mothers.
      Distinct Drosophila melanogaster populations from Brazil exhibit variable male
      killing Spiroplasma prevalences. In this study, we investigated the presence of
      variability for the male-killing phenotype among Drosophila and/or Spiroplasma
      strains and verified if it correlates with the endosymbiont prevalence in natural
      populations. For that, we analyzed the male-killing expression when Spiroplasma
      strains from different populations were transferred to a standard D. melanogaster
      line (Canton-S) and when a common Spiroplasma strain was transferred to different
      wild-caught D. melanogaster lines, both at optimal and challenging temperatures
      for the bacteria. No variation was observed in the male-killing phenotype induced
      by different Spiroplasma strains. No phenotypic variability among fly lines was
      detected at optimal temperature (23  degrees C), as well. Conversely, significant
      variation in the male-killing expression was revealed among D. melanogaster lines
      at 18.5  degrees C, probably caused by imperfect transmission of the
      endosymbiont. Distinct lines differed in their average sex ratios as well as in
      the pattern of male-killing expression as the infected females aged. Greater
      variation occurred among lines from one locality, although there was no clear
      correlation between the male-killing intensity and the endosymbiont prevalence in
      each population. Imperfect transmission or male killing may also occur in the
      field, thus helping to explain the low or intermediate prevalences reported in
      nature. We discuss the implications of our results for the dynamics of male
      killing Spiroplasma in natural populations.

PMID- 24121801
TI  - Airborne bacterial populations above desert soils of the McMurdo Dry Valleys,
      Antarctica.
AB  - Bacteria are assumed to disperse widely via aerosolized transport due to their
      small size and resilience. The question of microbial endemicity in isolated
      populations is directly related to the level of airborne exogenous inputs, yet
      this has proven hard to identify. The ice-free terrestrial ecosystem of
      Antarctica, a geographically and climatically isolated continent, was used to
      interrogate microbial bio-aerosols in relation to the surrounding ecology and
      climate. High-throughput sequencing of bacterial ribosomal RNA (rRNA) genes was
      combined with analyses of climate patterns during an austral summer. In general
      terms, the aerosols were dominated by Firmicutes, whereas surrounding soils
      supported Actinobacteria-dominated communities. The most abundant taxa were also
      common to aerosols from other continents, suggesting that a distinct bio-aerosol
      community is widely dispersed. No evidence for significant marine input to
      bioaerosols was found at this maritime valley site, instead local influence was
      largely from nearby volcanic sources. Back trajectory analysis revealed transport
      of incoming regional air masses across the Antarctic Plateau, and this is
      envisaged as a strong selective force. It is postulated that local soil microbial
      dispersal occurs largely via stochastic mobilization of mineral soil
      particulates.

PMID- 24121802
TI  - Ecological niche modelling of potential West Nile virus vector mosquito species
      and their geographical association with equine epizootics in Italy.
AB  - In Italy, West Nile virus (WNV) equine outbreaks have occurred annually since
      2008. Characterizing WNV vector habitat requirements allows for the
      identification of areas at risk of viral amplification and transmission. Maxent
      based ecological niche models were developed using literature records of 13
      potential WNV Italian vector mosquito species to predict their habitat
      suitability range and to investigate possible geographical associations with WNV
      equine outbreak occurrence in Italy from 2008 to 2010. The contribution of
      different environmental variables to the niche models was also assessed. Suitable
      habitats for Culex pipiens, Aedes albopictus, and Anopheles maculipennis were
      widely distributed; Culex modestus, Ochlerotatus geniculatus, Ochlerotatus
      caspius, Coquillettidia richiardii, Aedes vexans, and Anopheles plumbeus were
      concentrated in north-central Italy; Aedes cinereus, Culex theileri, Ochlerotatus
      dorsalis, and Culiseta longiareolata were restricted to coastal/southern areas.
      Elevation, temperature, and precipitation variables showed the highest predictive
      power. Host population and landscape variables provided minor contributions. WNV
      equine outbreaks had a significantly higher probability to occur in habitats
      suitable for Cx. modestus and Cx. pipiens, providing circumstantial evidence that
      the potential distribution of these two species coincides geographically with the
      observed distribution of the disease in equines. 

PMID- 24121803
TI  - Is automated electronic surveillance for healthcare-associated infections
      accurate in the burn unit?
AB  - As monitoring requirements for healthcare-acquired infection increase, an
      efficient and accurate method for surveillance has been sought. The authors
      evaluated the accuracy of electronic surveillance in multiple intensive care unit
      settings. Data from 500 intensive care unit patients were reviewed to determine
      the presence of central line-associated blood stream infection (CLABSI) and
      catheter-associated urinary tract infection (CAUTI). An electronic surveillance
      report was obtained to determine whether patients had a blood-line nosocomial
      infection marker or a urine nosocomial infection marker. Manual review was based
      on Centers for Disease Control and Prevention criteria. An infection
      preventionist then reviewed all discrepant cases and made a final determination,
      which was used as the gold standard. Sensitivity, specificity, false-positive
      rate, and false-negative rate were then calculated for electronic surveillance.
      In the burn population the sensitivity of electronic surveillance for CAUTI was
      66.66%, specificity 96.5%, false-positive rate 3.44%, false-negative rate 33%;
      and for CLABSI the sensitivity was 100%, specificity 95%, false-positive rate
      4.96%, false-negative rate 0%. In the nonburn population the sensitivity for
      CAUTI was 50%, specificity 97.9%, false-positive rate 2%, and false-negative rate
      30%; and for CLABSI sensitivity was 60%, specificity 98.8%, false-positive rate
      1%, and false-negative rate 60%. Burn centers may experience a higher false
      positive rate for electronic surveillance of CLABSI and CAUTI than other critical
      care units. 

PMID- 24121804
TI  - Reducing postburn injury anemia in a Jehovah's Witness patient.
AB  - Anemia is a complication of severe burn injury. Burn patients who refuse blood
      transfusions, such as Jehovah's Witnesses, present difficult challenges, and
      treatment paradigms need to be altered to reduce blood loss and increase red cell
      restoration. In this report the authors present a case of a 36-year-old Jehovah's
      Witness who suffered a 35% TBSA burn injury. In addition to standard burn injury
      treatment, the authors attempted to reduce blood loss with a combination of
      intraoperative (tranexamic acid) and perioperative (erythropoietin, intravenous
      iron) strategies. 

PMID- 24121805
TI  - From Baghdad to Boston: international transfer of burned children in time of war.
AB  - A large portion of the casualties admitted to military hospitals on the
      battlefield in Iraq consists of children, of whom 13% had burns. The U.S. Army
      Combat Support Hospital (CSH) in Baghdad, faced with an influx of such patients,
      successfully transferred selected burned children by commercial airlines to the
      Shriners Hospital for Children in Boston, Massachusetts (SHC-B). The authors
      aimed to document this process, from both an ethical and a procedural standpoint.
      Care was conducted in six phases: (1) admission to the CSH; (2) selection for
      transfer; (3) burn care at the CSH; (4) travel to the United States; (5) burn
      care at the SHC-B; (6) return to Iraq. Transfer and SHC-B care were funded by
      charitable organizations. A review of patient records was performed. Eight
      acutely burned pediatric patients participated in this program. All were
      successfully transferred, treated at SHC-B, and returned to Iraq. They ranged in
      age from 1.7 to 17 years and in burn size from 6 to 53% of the TBSA. At SHC-B,
      the hospital length of stay was 14 to 132 days; up to 23 visits to the operating
      room were performed for acute and reconstructive burn surgery. The cost of war
      includes the care of injured civilians, and includes burned children. For
      selected patients, transfer out of the combat zone is one method of fulfilling
      this obligation.

PMID- 24121806
TI  - Cost-effectiveness comparison between topical silver sulfadiazine and enclosed
      silver dressing for partial-thickness burn treatment.
AB  - The standard treatment of partial-thickness burns includes topical silver
      products such as silver sulfadiazine (SSD) cream and enclosed dressings including
      silver-impregnated foam (Mepilex Ag; Molnlycke Health Care, Gothenburg, Sweden)
      and silver-laden sheets (Aquacel Ag; ConvaTec, Skillman, NJ). The current state
      of health care is limited by resources, with an emphasis on evidence-based
      outcomes and cost-effective treatments. This study includes a decision analysis
      with an incremental cost-utility ratio comparing enclosed silver dressings with
      SSD in partial-thickness burn patients with TBSA less than 20%. A comprehensive
      literature review was conducted to identify clinically relevant health states in
      partial-thickness burn patients. These health states include successful healing,
      infection, and noninfected delayed healing requiring either surgery or
      conservative management. The probabilities of these health states were combined
      with Medicare CPT reimbursement codes (cost) and patient-derived utilities to fit
      into the decision model. Utilities were obtained using a visual analog scale
      during patient interviews. Expected cost and quality-adjusted life years (QALYs)
      were calculated using the roll-back method. The incremental cost-utility ratio
      for enclosed silver dressing relative to SSD was $40,167.99/QALY. One-way
      sensitivity analysis of complication rates confirmed robustness of the model.
      Assuming a maximum willingness to pay $50,000/QALY, the complication rate for SSD
      must be 22% or higher for enclosed silver dressing to be cost effective. By
      varying complication rates for SSD and enclosed silver dressings, the two-way
      sensitivity analysis demonstrated the cost effectiveness of using enclosed silver
      dressing at the majority of complication rates for both treatment modalities.
      Enclosed silver dressings are a cost-effective means of treating partial
      thickness burns. 

PMID- 24121808
TI  - Total heterotopic ossification of an acellular dermal matrix used for abdominal
      wall reconstruction.
AB  - Heterotopic ossification is an observable phenomenon in the setting of abdominal
      wounds, estimated to effect 25% of all patients after midline abdominal surgery.
      The development of acellular dermal matrices has revolutionised the approach in
      repairing abdominal hernias, especially for potentially contaminated wounds. We
      describe a case of heterotopic bone formation incorporating the whole of an
      acellular dermal matrix in a patient on chronic steroid therapy. 

PMID- 24121809
TI  - Tearing while bowling.

PMID- 24121807
TI  - Two aspartate residues at the putative p10 subunit of a type II metacaspase from
      Nicotiana tabacum L. may contribute to the substrate-binding pocket.
AB  - Metacaspases are cysteine proteases present in plants, fungi, prokaryotes, and
      early branching eukaryotes, although a detailed description of their cellular
      function remains unclear. Currently, three-dimensional (3D) structures are only
      available for two metacaspases: Trypanosoma brucei (MCA2) and Saccharomyces
      cerevisiae (Yca1). Furthermore, metacaspases diverged from animal caspases of
      known structure, which limits straightforward homology-based interpretation of
      functional data. We report for the first time the identification and initial
      characterization of a metacaspase of Nicotiana tabacum L., NtMC1. By combining
      domain search, multiple sequence alignment (MSA), and protein fold-recognition
      studies, we provide compelling evidences that NtMC1 is a plant metacaspase type
      II, and predict its 3D structure using the crystal structure of two type I
      metacaspases (MCA2 and Yca1) and Gsu0716 protein from Geobacter sulfurreducens as
      template. Analysis of the predicted 3D structure allows us to propose Asp353, at
      the putative p10 subunit, as a new member of the aspartic acid triad that
      coordinates the P1 arginine/lysine residue of the substrate. Nevertheless, site
      directed mutagenesis and expression analysis in bacteria and Nicotiana
      benthamiana indicate the functionality of both Asp348 and Asp353. Through the co
      expression of mutant and wild-type proteins by transient expression in N.
      benthamiana leaves we found that polypeptide processing seems to be
      intramolecular. Our results provide the first evidence in plant metacaspases
      concerning the functionality of the putative p10 subunit.

PMID- 24121810
TI  - Enamel microabrasion for aesthetic management of dental fluorosis.
AB  - Fluorosis has increased in recent times due to fluoridation of drinking water and
      addition of fluoride to various edible items, which leads to unaesthetic
      appearance of teeth visible at close quarters. The enamel microabrasion technique
      is a conservative method that improves the appearance of the teeth by restoring
      bright and superficial smoothness, without causing significant structural loss.
      The aim of this article is to describe an easy technique for managing mild to
      moderate dental fluorosis using Opalustre (Ultradent Products) microabrasion
      slurry. This conservative approach may be considered an interesting alternative
      to more invasive prosthetic techniques like composite resin restorations, ceramic
      veneers or crown fabrications. 

PMID- 24121811
TI  - Overdrive pacing in a patient with incessant torsades de pointes.
AB  - A 75-year-old man presented to the emergency department (ED) for syncope and was
      found to have intermittent runs of torsades de pointes (TdP). The patient had a
      medical history significant for disseminated coccidiomycosis and was on
      prophylactic fluconazole. Forty-eight hours prior to presentation, the patient
      had intractable nausea and vomiting and was unable to take anything orally. He
      eventually presented to the ED with severe hypokalaemia and hypomagnesaemia with
      repeat symptomatic runs of TdP, which required overdrive transvenous pacing.
      During the patient''s admission, his electrolytes were aggressively replete.
      Fluconazole was discontinued, and prior to discharge, the patient recovered fully
      with ECGs showing a normalisation of the QT interval. 

PMID- 24121812
TI  - Huge undifferentiated fibroblastic sarcoma of the foot and lower leg: impact of
      diagnostic delay and discussion of an entity.
AB  - We report a case of a 40-year-old female patient with a huge fibroblastic
      differentiated sarcoma of the left foot. After sampling all clinical,
      pathological and imaging information, the case was presented to the
      interdisciplinary tumour conference. Further treatment and medical care took
      place in the department of orthopaedics and orthopaedic surgery of our university
      hospital. Treatment consisted of amputation of the left foot and lower leg as an
      extremity-preserving surgical procedure was not possible because clear surgical
      margins could not be achieved with preservation of a functional rest of ankle and
      foot. Till date, no metastases have occurred. 

PMID- 24121813
TI  - Prosthesis on prosthesis: three-fourth metal crowns--a novel approach for
      metallic occlusion.
AB  - Single complete denture is a common occurrence which needs special attention in
      treatment. Denture reinforcement with metallic occlusion is recommended to
      prevent fracture of denture and wearing of artificial teeth. Various methods have
      been reported in the literature for metallic occlusion, which either compromise
      on aesthetics of the premolar teeth or need repeated procedures. This case
      reports the use of three-fourths metal crowns to achieve metallic occlusions in
      single complete denture. 

PMID- 24121814
TI  - A rare cystic lesion of the neck: parathyroid cyst.
AB  - Parathyroid cysts are rarely observed neck masses. Their physical examination is
      not specific and preoperative diagnosis is usually difficult. Imaging findings
      and ultrasound-guided fine-needle aspiration with hormone analysis evaluation are
      important diagnostic criteria. A 48-year-old female patient admitted to our
      hospital with a symptom of swelling on the left side of the neck was diagnosed
      with parathyroid cyst by imaging methods (ultrasonography, MRI, parathyroid
      scintigraphy) and laboratory findings. Fine-needle aspiration biopsy was
      performed and because of relapse on the follow-up sclerotherapy was planned. Our
      aim in this study was to present the radiological findings of this case of
      parathyroid cyst. 

PMID- 24121816
TI  - Vanishing corneal vessels.
AB  - We wish to highlight the importance of acknowledging the accompanying effects of
      topical phenylephrine drops on the eye other than its intended mydriasis. We
      reported a case of a 92-year-old woman with a corneal graft who was noted to have
      superficial corneal vascularisation which was not documented previously. After
      the instillation of topical tropicamide 1% and phenylephrine 2.5%, for
      funduscopy, the corneal vascularisation was not visible. When reassessed on
      another visit, tropicamide had no effect on the vessels and only phenylephrine
      did. We wish to highlight that when reviewing patients in cornea clinics,
      instilling phenylephrine prior to being seen may mask important corneal
      vascularisation. 

PMID- 24121815
TI  - Cotyledonoid dissecting leiomyoma as a possible cause of chronic lower back pain.
AB  - Uterine fibroids having the distinct pathological and immunohistochemical
      features of cotyledonoid dissecting leiomyoma have been reported infrequently. We
      describe a postmenopausal woman with an incidental finding of an abdominopelvic
      mass arising from the uterine fundus on routine radiological imaging of the
      lumbar spine. The imaging was performed for the investigation of chronic
      radicular lower back pain refractory to usual pain management. However, the woman
      did not manifest any gynaecological symptoms. Intraoperatively, the pelvic mass
      appeared malignant and a frozen section suggested uterine sarcoma. As such, the
      mass was radically resected, resulting in significant resolution of the back
      pain. To the authors' knowledge, this is the first report of cotyledonoid
      dissecting leiomyoma presenting solely as chronic lower back pain, and also the
      first report of this fibroid variant in Australasia. We discuss the diagnostic
      and operative challenges, emphasising the role of radiological imaging and
      immunohistopathology in such cases and review current literature. 

PMID- 24121817
TI  - Role of focal salvage ablative therapy in localised radiorecurrent prostate
      cancer.
AB  - Up to one-third of men can fail radical external beam radiotherapy for primary
      prostate cancer. Most of these men have expectant management with delayed
      hormones. However, around half of these men have localised recurrence. Challenges
      remain in identifying such men accurately, in order to enable them to undergo
      local salvage therapy which is potentially curative. Currently, this includes
      radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as
      cryotherapy and high intensity focused ultrasound, all of which can carry
      significant morbidity. New approaches may involve targeting the area of
      recurrence alone--focal salvage therapy--in order to reduce tissue damage and
      thus reduce morbidity. This requires accurate localisation of intraprostatic
      recurrent disease and precision targeted ablation.

PMID- 24121819
TI  - What is the true prevalence of carpal tunnel syndrome among US workers?

PMID- 24121818
TI  - Prevalence of baseline chronic kidney disease in 2,769 Chinese patients with
      renal cancer: nephron-sparing treatment is still underutilized.
AB  - PURPOSE: To evaluate the prevalence of baseline chronic kidney disease (CKD) in a
      large cohort of patients with renal masses in a single Chinese institution.
      Estimated glomerular filtration rate (eGFR) and CKD stage are more clinically
      relevant to predict the risk of morbidity and mortality in patients after
      nephrectomy. But, sCr reflects renal function poorly. METHODS: We retrospectively
      identified patients undergoing kidney surgery between January 2002 and June 2012.
      eGFR was calculated using the modification of diet in renal disease formulas
      modified based on Chinese people. CKD stages I-V were defined using the National
      Kidney Foundation definitions. RESULTS: A total of 2769 patients had adequate
      data available to calculate a preoperative eGFR (mL/min/1.73m2) with renal cancer
      confirmed by pathology. Of all patients, 97.7 % awaiting surgery at our
      institution had a "normal" baseline sCr (<=1.4 mg/dL), and 3.2 % of patients had
      CKD stage III or worse. Of the 401 patients >=70 years old, 16.7 % (67/401) had
      CKD stage III. CONCLUSION: Many patients with a seemingly normal sCr have CKD
      stage III or worse, especially in patients over 70 years old. Given the high
      prevalence of baseline CKD in patients with renal cancer, it is important to
      preserve renal parenchyma when treating them surgically.

PMID- 24121820
TI  - Multimedia modeling of the fate of triclosan and triclocarban in the Dongjiang
      River Basin, South China and comparison with field data.
AB  - Triclosan (TCS) and triclocarban (TCC) are two active ingredients widely used in
      many home and personal care products. Multimedia fate of TCS and TCC in the
      Dongjiang River basin, South China were addressed by the developed level III
      fugacity model based on their usage. Under the assumption of steady state, the
      concentrations in air, water, soil, sediment, suspended particulate matter (SPM)
      and fish as well as transfer flux across the interface between the compartments
      were simulated. The measured concentrations for the two compounds in water, SPM,
      and sediment from field monitoring campaigns were then compared to validate the
      model. The results showed that the model predicted reasonably accurate
      concentrations and the differences between the measured and modeled
      concentrations were all less than 0.7 log units. TCS and TCC had a tendency to
      distribute into the sediment phase, which accounted for more than 66.3% and 90.3%
      of the total masses, respectively. Wastewater discharge was the main source for
      the occurrence of the two compounds in the aquatic environment, while degradation
      was the primary process for the loss in the study area, followed by the advection
      export. Sensitivity analysis showed that the most influential parameters for the
      fate of the target chemicals were source term, degradation rates and adsorption
      coefficients. Monte Carlo simulation could well describe the modeling uncertainty
      and variability. 

PMID- 24121821
TI  - Neutrophil-lymphocyte ratio as a new predictive and prognostic factor at the
      hearing loss of diabetic patients.
AB  - Diabetes mellitus (DM) is a systemic inflammatory disease. Sensorineural hearing
      loss (SNHL) is seen more frequently in diabetic patients and it is believed that
      vascular complications of DM may be the cause of SNHL via inflammation.
      Neutrophil-to-lymphocyte ratio (NLR) was defined as a novel-potential marker to
      determine inflammation. We aimed to investigate the relationship between NLR
      levels and SNHL in diabetic patients using high-frequency audiometry (8-16 kHz)
      for the first time. The study included 58 patients diagnosed with DM. The control
      group was composed of 45 age-sex-BMI-matched healthy subjects. An automated blood
      cell counter was used for NLR measurements. The hearing assessments of the
      patients were carried out by Interacoustics Clinical Audiometer AC 40 device. The
      mean NLR values of the patients were significantly higher than the control group
      (p = 0.015). Speech recognition threshold values were higher and the speech
      discrimination values were lower in patients (p = 0.002, p < 0.001),
      respectively. Pure tone average of the patients at 500, 1,000, 2,000 Hz
      frequencies was divided into two groups (group 1 >25 dB and group 2 <25 dB). NLR
      levels of the diabetic patients with >25 dB were higher than the other diabetics
      (p = 0.007). In conclusion, while diabetic patients are evaluating, audiologic
      assessments of these patients should be performed because they are at more risk
      of SNHL and NLR may be considered as a predictive and prognostic marker of
      hearing loss or its beginning in these patients as a useful and reliable marker
      without any cost.

PMID- 24121822
TI  - Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell
      cancer: a retrospective analysis of a tertiary institute experience.
AB  - Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted
      standard of care in head and neck squamous cell carcinoma. However, this regimen
      is associated with severe toxicities with devastating effects on patients.
      Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce
      toxicities. The main objective of the present study is to identify the dose
      intensities and toxicities of weekly cisplatin in patients treated in a tertiary
      centre over a 12 month period. Included patients had squamous cell carcinoma
      arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were
      excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis
      or if they had prior treatment for head and neck cancer excluding neck
      dissection. During the study period, 52 patients met the inclusion criteria and
      their data were retrospectively obtained from the patients' database of St James
      hospital, Dublin. The median age of the study cohort was 54 years (range 33-73).
      Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary
      tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in
      10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage
      IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in
      35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved
      in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six
      cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37
      (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis,
      which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4
      neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively.
      The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %)
      patients. There was no grade 3 or 4 renal toxicity among the study cohort,
      although grade 2 was observed in six (11.5 %) patients. Death occurred in one
      patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is
      associated with moderate to severe toxicities and might lead to suboptimal
      chemotherapy delivery. More prospective clinical studies are required to
      determine the optimal chemoradiation regimen in head and neck squamous cell
      carcinoma.

PMID- 24121823
TI  - First-principles modeling of C60-Cr-graphene nanostructures for supporting metal
      clusters.
AB  - We present a first-principles modeling study of a new class of nanomaterials in
      which buckminsterfullerene (C60) and graphene (G) are bridged by Cr via
      coordination bonds. Two nanostructures denoted as G(C54)-Cr-C60 and G(C150)-Cr
      C60 are investigated, which share many similarities in the configuration
      geometries but differ in the distribution densities of Cr-C60 on the graphene
      surface. The binding energies between C60 and the rest of the system in these
      complexes are calculated to be 2.59 and 2.10 eV, respectively, indicative of
      their good structural stability. Additional spin-polarized calculations indicate
      that G(C54)-Cr-C60 is weakly ferromagnetic, which is chiefly due to the
      contribution from the 3d shell of Cr. We then investigate three model complexes
      of C60-Cr-G(C54) and a metal cluster (Ni4, Pd4, or Pt4). The binding energies of
      these three nanostructures are significantly large (3.57, 2.38, and 4.35 eV,
      respectively). Electron density analysis along the Ni-C, Pd-C, and Pt-C bonds
      consistently affirms that the Pt-C bond is the strongest while the Pd-C bond is
      the weakest. The strong Pt-C bond is attributed to the effective overlap of
      5d(z(2)) (Pt) and 2p(z) (C) orbitals. Partial density of states analysis
      indicates that Ni4 and Pd4 substantially contribute to the strong ferromagnetism
      of the complexes, whereas Pt4 is observed to be non-magnetic even when the spin
      orbit coupling is taken into account. H2 dissociation on the Ni4 complex is also
      examined, and the estimated reaction barrier is relatively low (0.76 eV).

PMID- 24121824
TI  - Direct confocal acquisition of fluorescence from X-gal staining on thick tissue
      sections.
AB  - X-gal staining is a common procedure used in the histochemical monitoring of gene
      expression by light microscopy. However, this procedure does not permit the
      direct confocal acquisition of images, thus preventing the identification of
      labelled cells on the depth (Z) axis of tissue sections and leading sometimes to
      erroneous conclusions in co-localization and gene expression studies. Here we
      report a technique, based on X-gal fluorescence emission and mathematically-based
      optical correction, to obtain high quality fluorescence confocal images. This
      method, combined with immunofluorescence, makes it possible to unequivocally
      identify X-gal-labelled cells in tissue sections, emerging as a valuable tool in
      gene expression and cell tracing analysis.

PMID- 24121825
TI  - Unicortical PEEK inset locking fixation for metacarpal fractures: a biomechanical
      study.
AB  - PURPOSE: There are numerous constructs employed in the treatment of metacarpal
      fractures with varying degrees of success. While plate fixation commonly involves
      dorsal application of a bicortical non-locking plate, there has been recent
      exploration of other fixation options including unicortical locked plating. The
      purpose of this study was to evaluate the biomechanical integrity of a
      polyetheretherketone (PEEK) inset locking plate and, in doing so, compare it to
      standard plate fixation (utilizing a clinically proven bicortical non-locking
      titanium plate) in a simulated porcine metacarpal fracture model. METHODS:
      Reproducible mid-shaft fractures were created in porcine second metacarpals. The
      fractured specimens were reduced and plated with either a bicortical non-locking
      plate or a unicortical locking plate with a PEEK locking design. Constructs were
      then loaded to failure in the same fashion as performed to create the fracture.
      Peak load was measured as the apex on the load-to-failure deflection curve.
      Stiffness was calculated as the linear slope on the load-to-failure deflection
      curve. Data were analyzed via Student's t test. RESULTS: Unicortical locking
      constructs failed at 344 +/- 119 N, while bicortical non-locking constructs were
      found to fail at 277 +/- 101 N (p = 0.19). The unicortical locking constructs
      demonstrated a stiffness of 80 +/- 36 N/mm compared with the bicortical non
      locking constructs (69 +/- 36 N/mm) although again the difference was not found
      to be statistically different (p = 0.49). CONCLUSION: Based on this study, a
      locked plating construct using a polymer mechanism provides an interesting new
      locking fixation method for small bone fractures and with our limited number of
      specimens tested, provided at least a similar strength and rigidity profile in
      comparison with bicortical fixation in the treatment of metacarpal fractures.

PMID- 24121826
TI  - Ethanol and formaldehyde fixation irreversibly alter bones' organic matrix.
AB  - INTRODUCTION: Biomechanical tests on bones are frequently accomplished in
      anatomically fixed tissues. The effects of ethanol or formaldehyde based fixation
      in bone material properties are subject to controversial discussions, regarding
      their appropriateness and usability to answer clinical questioning or
      biomechanical issues. We hypothesized that ethanol and formaldehyde irreversibly
      change bone material properties, and that this effect is mainly related to the
      bone's organic matrix. MATERIAL AND METHODS: Fixation related alterations in
      material properties were investigated in six fresh and two macerated human coxal
      bones by means of three-dimensional laser vibrometry based modal analysis.
      Ethanol or formaldehyde fixation were performed in one macerated and three
      unfixed specimens each. Changes in specimen weight and modal frequencies related
      to fixation, rinsing and drying were obtained. Modal assurance criterion (MAC)
      values were recorded to determine altered bone anisotropy. RESULTS: Due to
      fixation, modal frequencies were irreversibly altered in unfixed specimens,
      indicating weight loss in ethanol and structural changes in formaldehyde fixed
      specimens. In the macerated and inorganic controls, fixation related weight and
      modal frequency changes were reversible by rinsing. In the unfixed specimens,
      bone anisotropy was irreversibly altered by both modes of fixation, whereas the
      fixation related changes in bony anisotropy were reversible in the macerated
      controls after rinsing. DISCUSSION: Anatomical fixation that includes ethanol or
      formaldehyde irreversibly alters material properties of unfixed bones and impacts
      bone anisotropic properties, caused by changes in the organic matrix. In
      macerated bones that exclusively consisted of inorganic mineral salts, the
      observed effects on material properties and anisotropy were reversible.
      Conclusively, anatomical fixation on basis of ethanol or formaldehyde cannot be
      recommended, if material characteristics close to the vital state are of
      interest. Modal analysis is a potential method to gain insight into material
      properties, revealing the influence of the organic bone matrix on coxal bone
      elasticity.

PMID- 24121827
TI  - In situ synthesized TiB-TiN reinforced Ti6Al4V alloy composite coatings:
      microstructure, tribological and in-vitro biocompatibility.
AB  - Wear resistant TiB-TiN reinforced Ti6Al4V alloy composite coatings were deposited
      on Ti substrate using laser based additive manufacturing technology. Ti6Al4V
      alloy powder premixed with 5wt% and 15wt% of boron nitride (BN) powder was used
      to synthesize TiB-TiN reinforcements in situ during laser deposition. Influences
      of laser power, scanning speed and concentration of BN on the microstructure,
      mechanical, in vitro tribological and biological properties of the coatings were
      investigated. Microstructural analysis of the composite coatings showed that the
      high temperature generated due to laser interaction with Ti6Al4V alloy and BN
      results in situ formation of TiB and TiN phases. With increasing BN
      concentration, from 5wt% to 15wt%, the Young's modulus of the composite coatings,
      measured by nanoindentation, increased from 170+/-5GPa to 204+/-14GPa. In vitro
      tribological tests showed significant increase in the wear resistance with
      increasing BN concentration. Under identical test conditions TiB-TiN composite
      coatings with 15wt% BN exhibited an order of magnitude less wear rate than CoCrMo
      alloy-a common material for articulating surfaces of orthopedic implants. Average
      top surface hardness of the composite coatings increased from 543+/-21HV to 877+/
      75HV with increase in the BN concentration. In vitro biocompatibility and flow
      cytometry study showed that these composite coatings were non-toxic, exhibit
      similar cell-materials interactions and biocompatibility as that of commercially
      pure titanium (CP-Ti) samples. In summary, excellent in vitro wear resistance,
      high stiffness and suitable biocompatibility make these composite coatings as a
      potential material for load-bearing articulating surfaces towards orthopaedic
      implants. 

PMID- 24121832
TI  - Evaluating the Labour Government's English NHS health system reforms: the 2008
      Darzi reforms.
AB  - Starting in 2002, the UK Labour Government of 1997-2010 introduced a series of
      changes to the National Health Service (NHS) in England designed to increase
      patients' choices of the place of elective hospital care and encourage
      competition among public and private providers of elective hospital services for
      NHS-funded patients. In 2006, the Department of Health initiated the Health
      Reform Evaluation Programme (HREP) to assess the impact of the changes. In June
      2008, the White Paper, High quality care for all, was published. It represented
      the government's desire to focus the next phase of health care system reform in
      England as much on the quality of care as on improving its responsiveness and
      efficiency. The 2008 White Paper led to the commissioning of a further wave of
      evaluative research under the auspices of HREP, as follows: an evaluation of the
      implementation and outcomes of care planning for people with long-term
      conditions; an evaluation of the personal health budget pilots; an evaluation of
      the implementation and outcomes of the Commissioning for Quality and Innovation
      (CQUIN) framework; and an evaluation of cultural and behavioural change in the
      NHS focused on ensuring high quality care for all. This Supplement includes
      papers from each project. The evaluations present a mixed picture of the impact
      and success of the 2008 reforms. All the studies identify some limitations of the
      policies in the White Paper. The introduction of personal health budgets appears
      to have been the least problematic and, depending on assumptions, likely to be
      cost-effective for the sorts of patients involved in the pilot. For the rest of
      the changes, impacts ranged from little or none (CQUIN and care planning for
      people with chronic conditions) to patchy and highly variable (instilling a
      culture of quality in acute hospitals) in the three years following the
      publication of the White Paper. On the other hand, each of the studies identifies
      important insights relevant to modifying and improving the policies. These
      findings have continuing relevance since both the 2008 White Paper's policies,
      and the issues they were focused on remedying, remain central to the current
      Coalition Government's reform agenda.

PMID- 24121831
TI  - Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with
      patient survival.
AB  - BACKGROUND: Extensive evidence implicates the Eph receptor family of tyrosine
      kinases and its ligand, ephrin, in glioma invasion, but it remains incompletely
      understood how these receptors affect chemotactic behavior of glioma. We sought
      to identify the Eph family members that correlate with patients' survival and to
      reveal the function of Eph in glioma invasion. METHODS: Clinical relevance of
      EphB genes was confirmed in a clinically annotated expression data set of 195
      brain biopsy specimens. The function of EphB was analyzed in vitro and in vivo.
      RESULTS: Levels of mRNA of certain EphB members were significantly different in
      histological grades of glioma. According to Kaplan-Meier analysis, only the EphB1
      level among 5 members of EphB emerged to be a powerful predictor of favorable
      survival in malignant glioma (n = 97, P = .0048), although the levels of EphB1
      expression did not vary across the tumor grades. Immunoprecipitation showed that
      tyrosine phosphorylated EphB1 was not detected in all glioma cells tested. Forced
      overexpression and autophosphorylation of EphB1 in low expressor cell lines
      (U251, U87) did not affect cell migration or invasion in vitro, whereas EphB1
      phosphorylation induced by ephrin-B2/Fc significantly decreased migration and
      invasion. Cells expressing ephrin-B2 showed noteworthy morphological changes
      consistent with migration induction; this alteration was negated by EphB1
      overexpression. Concomitantly, overexpression of EphB1 abrogated the increased
      migration and invasion induced by ephrin-B2 in vitro and in vivo. CONCLUSIONS:
      These data suggest that ligand-dependent EphB1 signaling negatively regulates
      glioma cell invasion, identifying EphB1 as a favorable prognostic factor in
      malignant glioma.

PMID- 24121833
TI  - 'New' and distributed leadership in quality and safety in health care, or 'old'
      and hierarchical? An interview study with strategic stakeholders.
AB  - OBJECTIVES: We aimed to explore the views of strategic level stakeholders on
      leadership for quality and safety in the UK National Health Service. METHODS: We
      interviewed 107 stakeholders with close involvement in quality and safety as
      professionals, managers, policy makers or commentators. Analysis was based on the
      constant comparative method. RESULTS: Participants identified the crucial role of
      leadership in ensuring safe, high quality care. Consistent with the academic
      literature, participants distinguished between traditional hierarchical
      'concentrated' leadership associated with particular positions, and distributed
      leadership involving those with particular skills and abilities across multiple
      institutional levels. They clearly and explicitly saw a role for distributed
      leadership, emphasizing that all staff had responsibility for leading on patient
      safety and quality. They described the particular value of leadership coalitions
      between managers and clinicians. However, concern was expressed that distributed
      leadership could mean confusion about who was in charge, and that at national
      level it risked creating a vacuum of authority, mixed messages, and conflicting
      expectations and demands. Participants also argued that hierarchically based
      leadership was needed to complement distributed leadership, not least to provide
      focus, practical support and expertise, and managerial clout. CONCLUSIONS:
      Strategic level stakeholders see the most effective form of leadership for
      quality and safety as one that blends distributed and concentrated leadership.
      Policy and academic prescriptions about leadership may benefit from the
      sophisticated and pragmatic know-how of insiders who work in organizations that
      remain permeated by traditional structures, cleavages and power relationships.

PMID- 24121834
TI  - Multimorbidity and delivery of care for long-term conditions in the English
      National Health Service: baseline data from a cohort study.
AB  - OBJECTIVES: Many patients with long-term conditions have multiple conditions.
      Current delivery of care is not designed around their needs and they may face
      barriers to effective self-management. This study assessed the relationships
      between multimorbidity, the delivery of care, and self-management. METHODS: We
      surveyed 2439 patients with long-term conditions concerning their experience of
      the delivery of care and self-management in England in 2011. We assessed
      multimorbidity in terms of a count of long-term conditions and the presence of
      'probable depression'. We explored the relationships between multimorbidity,
      patient experience of the delivery of care, and self-management RESULTS: Neither
      measure of multimorbidity was a significant predictor of patients' experience of
      the delivery of care. Patients with multimorbidity reported higher levels of self
      management behaviour, while the presence of depression was associated with less
      positive attitudes towards self-management. CONCLUSIONS: The current data do not
      demonstrate a consistent impact of multimorbidity on patients' experience of care
      or on self-management. Further research is required to assess those types of
      multimorbidity that are associated with significant deficits, or to identify
      other aspects of care that might be problematic in the context of multiple
      conditions.

PMID- 24121835
TI  - Should pay-for-performance schemes be locally designed? Evidence from the
      Commissioning for Quality and Innovation (CQUIN) Framework.
AB  - OBJECTIVES: It is increasingly recognized that the design characteristics of pay
      for-performance schemes are important in determining their impact. One important
      but under-studied design aspect is the extent to which pay-for-performance
      schemes reflect local priorities. The English Department of Health White Paper
      High Quality Care for All introduced a Commissioning for Quality and Innovation
      (CQUIN) Framework from April 2009, under which local commissioners and providers
      were required to negotiate and implement an annual pay-for-performance scheme. In
      2010/2011, these schemes covered 1.5% (L 1.0 bn) of NHS expenditure. Local design
      was intended to offer flexibility to local priorities and generate local
      enthusiasm, while retaining good design properties of focusing on outcomes and
      processes with a clear link to quality, using established indicators where
      possible, and covering three key domains of quality (safety; effectiveness;
      patient experience) and innovation. We assess the extent to which local design
      achieved these objectives. METHODS: Quantitative analysis of 337 locally
      negotiated CQUIN schemes in 2010/2011, along with qualitative analysis of 373
      meetings (comprising 800 hours of observation) and 230 formal interviews (audio
      recorded and transcribed verbatim) with NHS staff in 12 case study sites.
      RESULTS: The local development process was successful in identifying variation in
      local needs and priorities for quality improvement but the involvement of
      frontline clinical staff was insufficient to generate local enthusiasm around the
      schemes. The schemes did not in general live up to the requirements set by the
      Department of Health to ensure that local schemes addressed the original
      objectives for the CQUIN framework. CONCLUSIONS: While there is clearly an
      important case for local strategic and clinical input into the design of pay-for
      performance schemes, this should be kept separate from the technical design
      process, which involves defining indicators, agreeing thresholds, and setting
      prices. These tasks require expertise that is unlikely to exist in each locality.
      The CQUIN framework potentially offered an opportunity to learn how technical
      design influenced outcome but due to the high degree of local experimentation and
      little systematic collection of key variables, it is difficult to derive lessons
      from this unstructured experiment about the impact and importance of different
      technical design factors on the effectiveness of pay-for-performance. Balancing
      the policy goal of localism with the objective of improving patient outcomes
      leads us to conclude that a somewhat firmer national framework would be
      preferable to a fully locally designed framework.

PMID- 24121836
TI  - Choosing health: qualitative evidence from the experiences of personal health
      budget holders.
AB  - OBJECTIVES: Personal health budgets were piloted in the English National Health
      Service between 2009 and 2012. Semi-structured interviews with a sub-sample of
      early budget holders aimed to explore their experiences of receiving and using a
      budget. METHOD: Over 2000 people from 20 pilot sites were recruited to a multi
      method evaluation of the personal health budget pilots. A sub-sample of 58 people
      was selected for qualitative interviews three months after the offer of a budget;
      52 were re-interviewed six months later. The purposively selected sample
      reflected a range of health conditions, locality, age and gender. RESULTS:
      Personal health budgets were reported to have positive impacts on health, health
      care and relatives/family. Benefits often extended beyond the condition for which
      the budget had been awarded. However, interviewees rarely knew the level of their
      budget; some reported difficulty in agreeing acceptable uses for their budget;
      and delays could occur in procuring chosen services or equipment. CONCLUSION:
      Patients' experiences offer valuable insights for the roll-out of personal health
      budgets beyond the pilot phase. Flexibility in how budgets are used may allow
      maximum benefits to be derived. Clear information about what budgets can and
      cannot be used for, with suggestions offered, will be useful. People with newly
      diagnosed or recent sudden onset conditions may need more help to plan their
      support, but all budget holders are likely to benefit from regular contact with
      staff for reassurance and continued motivation.

PMID- 24121837
TI  - Single-plant, sterile microcosms for nodulation and growth of the legume plant
      Medicago truncatula with the rhizobial symbiont Sinorhizobium meliloti.
AB  - Rhizobial bacteria form symbiotic, nitrogen-fixing nodules on the roots of
      compatible host legume plants. One of the most well-developed model systems for
      studying these interactions is the plant Medicago truncatula cv. Jemalong A17 and
      the rhizobial bacterium Sinorhizobium meliloti 1021. Repeated imaging of plant
      roots and scoring of symbiotic phenotypes requires methods that are non
      destructive to either plants or bacteria. The symbiotic phenotypes of some plant
      and bacterial mutants become apparent after relatively short periods of growth,
      and do not require long-term observation of the host/symbiont interaction.
      However, subtle differences in symbiotic efficiency and nodule senescence
      phenotypes that are not apparent in the early stages of the nodulation process
      require relatively long growth periods before they can be scored. Several methods
      have been developed for long-term growth and observation of this host/symbiont
      pair. However, many of these methods require repeated watering, which increases
      the possibility of contamination by other microbes. Other methods require a
      relatively large space for growth of large numbers of plants. The method
      described here, symbiotic growth of M. truncatula/S. meliloti in sterile, single
      plant microcosms, has several advantages. Plants in these microcosms have
      sufficient moisture and nutrients to ensure that watering is not required for up
      to 9 weeks, preventing cross-contamination during watering. This allows
      phenotypes to be quantified that might be missed in short-term growth systems,
      such as subtle delays in nodule development and early nodule senescence. Also,
      the roots and nodules in the microcosm are easily viewed through the plate lid,
      so up-rooting of the plants for observation is not required. 

PMID- 24121839
TI  - Abstracts of the 51st ISCEV (International Society for Clinical Electrophysiology
      of Vision) International Symposium. October 13-17, 2013. Chongqing, China.

PMID- 24121838
TI  - Pathogen signatures activate a ubiquitination pathway that modulates the function
      of the metabolic checkpoint kinase mTOR.
AB  - The mammalian immune system has the ability to discriminate between pathogenic
      microbes and nonpathogenic microbes to control inflammation. Here we investigated
      the ubiquitination profiles of host proteins after infection of macrophages with
      a virulent strain of the intracellular bacterium Legionella pneumophila or a
      nonpathogenic mutant of L. pneumophila. Only infection with pathogenic L.
      pneumophila resulted in ubiquitination of positive regulators of the metabolic
      checkpoint kinase mTOR and led to diminished mTOR activity. Detection of pathogen
      signatures resulted in translational biasing toward proinflammatory cytokines
      through mTOR-mediated regulation of cap-dependent translation. Thus, there is a
      pathogen-detection program in macrophages that stimulates protein ubiquitination
      and the degradation of regulators of mTOR, which suppresses mTOR function and
      directs a proinflammatory cytokine program. 

PMID- 24121840
TI  - Sports hernia or groin disruption injury? Chronic athletic groin pain: a
      retrospective study of 100 patients with long-term follow-up.
AB  - INTRODUCTION AND OBJECTIVES: Chronic groin pain (athletic pubalgia) is a common
      problem in sports such as football, hockey, cricket, baseball and athletics.
      Multiple co-existing pathologies are often present which commonly include
      posterior inguinal canal wall deficiency, conjoint tendinopathy, adductor
      tendinopathy, osteitis pubis and peripheral nerve entrapment. The mechanism of
      injury remains unclear but sports that involve either pivoting on a single leg
      (e.g. kicking) or a sudden change in direction at speed are most often associated
      with athletic pubalgia. These manoeuvres place large forces across the bony
      pelvis and its soft tissue supports, accounting for the usual clinical
      presentation of multiple symptomatic abnormalities forming one pattern of injury.
      RESULTS: The diagnoses encountered in this series of 100 patients included rectus
      abdominis muscle atrophy/asymmetry (22), conjoint tendinopathy (16), sports
      (occult, incipient) hernia (16), groin disruption injury (16), classical hernia
      (11) traumatic osteitis pubis (5), and avulsion fracture of the pubic bone (4).
      Surgical management was generally undertaken only after failed conservative
      therapy of 3-6 months, but some professionals who have physiotherapy during the
      football season went directly to surgery at the end of the football season. A
      variety of operations were performed including groin reconstruction (15), open
      hernia repair with or without mesh (11), sports hernia repair (Gilmore) (7)
      laparoscopic repair (3), conjoint tendon repair (3) and adductor tenotomy (3).
      Sixty-six patients were available for follow at an average of 13 years after
      initial consultation and the combined success rate for both conservative
      treatment and surgery was 94%. CONCLUSION: The authors believe that athletic
      pubalgia or sports hernia should be considered as a 'groin disruption injury',
      the result of functional instability of the pelvis. The surgical approach is
      aimed at strengthening the anterior pelvic soft tissues that support and
      stabilise the symphysis pubis.

PMID- 24121842
TI  - Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.
AB  - We present a case of a combination of primary and secondary diaphragmatic hernia
      in a 63-year male patient. For progressive dyspnea and palpitations caused by a
      large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an
      open tension-free mesh repair was performed. The postoperative course was
      complicated by a secondary hepatothorax through a spontaneous rupture of the
      right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to
      be sufficient. This recurrent herniation might be a consequence of (1)
      preexisting atrophy of the right diaphragm caused by disposition and/or long-term
      diaphragmatic dysfunction due to the large hernia, combined with (2) further
      thinning out of the diaphragm by intraoperative hernia sac resection, and (3)
      postoperative increase of intra-abdominal pressure.

PMID- 24121841
TI  - Acutely incarcerated abdominal wall hernia: what if it is a consequence?
AB  - PURPOSE: The aim of this study was to emphasize the importance of differential
      diagnosis in patients with acutely incarcerated abdominal wall hernia (AWH).
      METHODS: The medical records of patients who underwent emergency surgery with
      preoperative diagnosis of acutely incarcerated AWH and in whom acutely
      incarcerated AWH was the consequence of increased intraabdominal pressure due to
      other abdominal emergencies were reviewed. The following data were collected:
      demographics, the duration between the onset of symptoms and admission, clinical
      findings, biochemical test results that were abnormal, radiological findings,
      preoperative and intraoperative diagnosis, operative findings, surgical
      procedure, different diagnosis made in the postoperative period, reoperation,
      morbidity, mortality, and the length of hospital stay. RESULTS: Ten patients were
      included to the study. The primary pathology was found to be perforated peptic
      ulcer disease in three, bowel obstruction due to neoplastic mass in three,
      complicated appendicitis in two, acute mesenteric ischemia in one, and acute
      diverticulitis in one. The correct diagnosis was made during emergency surgery
      for hernia repair, whereas the primary pathology was identified postoperatively
      in two patients. CONCLUSIONS: Patients who are diagnosed to have acutely
      incarcerated AWH preoperatively should undergo further diagnostic workup, if any
      level of clinical suspicion for differential diagnosis is present. Moreover, the
      surgeon should consider general abdominal exploration if contradictory findings
      are encountered during the exploration of the hernia sac, even if preoperative
      diagnostic studies reveal no gross pathology or non-specific findings.

PMID- 24121843
TI  - Supramolecular architecture, crystal structure and transport properties of the
      prototypal oxobenzene-bridged bisdithiazolyl radical conductor.
AB  - Supramolecular CHpi interactions cause a ruffling of the otherwise coplanar
      ribbon-like arrays of radicals in the structure of the oxobenzene-bridged
      bisdithiazolyl . The material displays a conductivity sigma(300 K) = 6 * 10(-3) S
      cm(-1) (Eact = 0.16 eV) and orders antiferromagnetically below 4 K. At applied
      fields above 1 kOe the material displays metamagnetic behavior. 

PMID- 24121845
TI  - Domestic violence: the role of the nurse.

PMID- 24121844
TI  - Three-dimensional framework of vigor, organization, and resilience (VOR) for
      assessing rangeland health: a case study from the alpine meadow of the Qinghai
      Tibetan Plateau, China.
AB  - Rangeland health assessments play an important role in providing qualitative and
      quantitative data about ecosystem attributes and rangeland management. The
      objective of this study is to test the feasible of a modified model and visualize
      the health in a three-dimensional model. A modified Costanza model was employed,
      and eight indicators, including the biomass, biodiversity, and carrying capacity
      [associated with the vigor, organization, and resilience (VOR)] were applied. An
      entropy method was also developed to calculate the weight of each indicator, and
      a three-dimensional framework was applied to visualize the indicators and health
      index. The conceptual model was demonstrated using data from a case study on the
      alpine rangeland of the Qinghai-Tibetan Plateau, one of the globally important
      grassland biomes being severely degraded by natural and human factors. The health
      indices of four grassland plots at different levels of degradation were
      calculated using a modified approach to measuring their VOR. The results
      indicated that the least disturbed plot was relatively healthy compared to the
      other plots. In addition, the health indices presented in the three-dimensional
      VOR framework decreased in a consistent manner across the four plots along the
      disturbance gradients. Such rangeland health assessments should be integrated
      with management efforts to insure their long-term sustainable use. 

PMID- 24121846
TI  - Bacterial vaginosis: risks and treatment.

PMID- 24121847
TI  - The UK pertussis epidemic: implications for immunisation.
AB  - The UK is currently experiencing an epidemic of pertussis (whooping cough), in
      spite of the fact that uptake of immunisation against this disease has remained
      consistently high for some time. The number of cases is far higher in adults and
      adolescents, but there has also been a huge increase in the burden of disease
      among infants under 3 months, in whom the outcome is potentially far more
      serious. Last year, 14 infants died from the disease, prompting the Joint
      Committee on Vaccination and Immunisation (JCVI) to recommend vaccination for all
      women in the third trimester of pregnancy. This article looks at the background
      to the current epidemic, outlining the history of the disease; the underpinning
      immunological principles that have influenced attempts to control its spread to
      date; the current immunisation schedule; and other possible measures being
      considered. 

PMID- 24121848
TI  - Service user and carer participation in an endoscopy nursing programme.
AB  - This article reports an initiative to improve students' insight into service user
      and carer experience of endoscopy, particularly those with severe disability,
      such as spinal cord injury. This insight has the potential to improve the
      information provided and level of person-centred care in an endoscopy service. It
      was evident in the feedback from the classroom encounter that the teaching and
      learning strategy had a positive outcome, which will allow us to integrate the
      approach into future curriculum development and delivery, bringing the lived
      experience from the service user and carer perspective into the classroom.
      Students engaged in discussion and used their reflective skills to develop
      sensitivity to those with physical disability and complex needs requiring
      endoscopy procedures. 

PMID- 24121849
TI  - Thrombolytic dosing in acute ischaemic stroke.
AB  - Thrombolysis treatment for acute ischaemic stroke is effective if it is
      administered within 4.5 hours of stroke onset. Alteplase is a licensed
      thrombolytic treatment for ischaemic stroke. The dose of alteplase is dependent
      on a patient's weight. The stroke team involved in the administration of the
      treatment usually estimates a patient's weight prior to the treatment in order to
      ensure the correct dosage. This paper highlights the reliability of body weight
      estimates in determining the accuracy of thrombolysis dosing and the implication
      of dosing errors to post-thrombolysed patients. 

PMID- 24121850
TI  - Cognitive behavioural therapy for psychosis and anxiety.
AB  - This article discusses the effectiveness of a cognitive behavioural therapy (CBT)
      group for clients with a first episode of psychosis, who were also experiencing
      comorbid symptoms of anxiety. Clients of 18-35 years of age who reported anxiety
      symptoms, either as a direct or indirect result of psychotic symptoms, were
      invited to attend a 12-week CBT-based group. The effectiveness of the
      intervention was evaluated at screening and 3-month follow-up with the
      Depression, Anxiety and Stress Scale (DASS-21) (Lovibond and Lovibond, 2004). The
      results showed a statistically significant improvement in symptoms (depression,
      p=0.06; anxiety, p=0.05; stress, p=.014), sustainable at 3-month follow-up. The
      authors concluded that a CBT group for people with a first episode of psychosis
      that focuses on the management of anxiety can be an effective and viable means of
      reducing levels of anxiety and associated stress and depression. This model is
      recommended for use by community mental health teams. 

PMID- 24121851
TI  - The role of healthcare strategies in controlling antibiotic resistance.
AB  - In an interview in March 2013, the Chief Medical Officer described antibiotic
      resistance as a 'ticking time bomb' and ranked it along with terrorism on a list
      of threats to the nation. Her report Infections and the Rise of Antimicrobial
      Resistance (Department of Health, 2011) highlighted that, while a new infectious
      disease has been discovered nearly every year over the past three decades, there
      have been very few new antibiotics developed, leaving our armoury nearly empty.
      Antibiotic resistance is a universal problem that needs to be tackled by a wide
      variety of strategies and players. Our approach to tackling resistance to
      antibiotic agents must therefore also be dynamic. As well as reducing
      environmental use, we also need to lower antibiotic use in the healthcare
      setting. Healthcare workers have a huge role to play in combating antibiotic
      resistance. This article focuses on several issues related to antibiotic
      resistance, including antibiotic modes of action and the properties that confer
      resistance on bacteria. It includes information on antibiotic usage and describes
      current healthcare strategies we can adopt to help reduce the development of
      resistance. 

PMID- 24121852
TI  - Lemierre's syndrome: the importance of early detection.
AB  - Sore throat is a common complaint, generally thought to be viral in origin, for
      which there may be a reluctance to prescribe antibiotics. This, combined with the
      emergence of antibiotic resistance, may explain the recent rise in the number of
      reports of Lemierre's syndrome (LS). LS characterises a postanginal septicaemia
      that is associated with significant morbidity and mortality if not recognised and
      treated early. This article describes the management of a 17-year-old boy
      diagnosed with LS to illustrate its classical presentation, common pitfalls in
      diagnosis and optimal management. 

PMID- 24121853
TI  - Clinical supervision: from staff nurse to nurse consultant. Part 6:
      implementation at a strategic level.

PMID- 24121855
TI  - Creating the hospital of the future: enabling the vision.

PMID- 24121854
TI  - Improving the safety of patients in England.

PMID- 24121856
TI  - Treatment options for myeloma.

PMID- 24121857
TI  - Professional boundaries in the nurse-patient relationship.
AB  - Complaints about failures to maintain professional boundaries are increasing,
      with the Nursing and Midwifery Council reporting some 247 new cases in the year
      2011-12. Professional boundaries are essential to effective nurse-patient
      relationships that must focus on care and treatment only. In this article the
      author outlines the scope of the nurse-patient relationship and reflects on
      activity considered as being outside the professional relationship. 

PMID- 24121858
TI  - Improving quality processes.

PMID- 24121859
TI  - LDH nanocages synthesized with MOF templates and their high performance as
      supercapacitors.
AB  - Layered double hydroxides (LDHs) are currently attracting intense research
      interest for their various applications. Three LDH hollow nano-polyhedra are
      synthesized with zeolitic imidazolate framework-67 (ZIF-67) nanocrystals as the
      templates. The nanocages well inherit the rhombic dodecahedral shape of the ZIF
      67 templates, and the shell is composed of nanosheets assembled with an edge-to
      face stacking. This is the first synthesis of the LDH non-spherical structures.
      And the mechanism of utilizing metal-organic framework (MOF) nanocrystals as
      templates is explored. Control of the simultaneous reactions, the precipitation
      of the shells and the template etching, is extremely crucial to the preparation
      of the perfect nanocages. And the Ni-Co LDH nanocages exhibit superior
      pseudocapacitance property due to their novel hierarchical and submicroscopic
      structures. 

PMID- 24121860
TI  - Coarse-graining DNA for simulations of DNA nanotechnology.
AB  - To simulate long time and length scale processes involving DNA it is necessary to
      use a coarse-grained description. Here we provide an overview of different
      approaches to such coarse-graining, focussing on those at the nucleotide level
      that allow the self-assembly processes associated with DNA nanotechnology to be
      studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly
      suited to this task, and has opened up this field to systematic study by
      simulations. We illustrate some of the range of DNA nanotechnology systems to
      which the model is being applied, as well as the insights it can provide into
      fundamental biophysical properties of DNA. 

PMID- 24121861
TI  - Group diabetes self-management education in a primary care setting: a quality
      improvement project.
AB  - This quality improvement project evaluated the effectiveness of a monthly
      diabetes self-management education intervention on HbA1C and knowledge levels in
      patients with type 2 diabetes mellitus. A retrospective analysis evaluating 51
      patients found no significant improvement in HbA1C levels; however, there was a
      significant improvement in knowledge levels. Race was an influential factor on
      HbA1C levels showing a significant elevation in mean HbA1C in African Americans,
      while there was a decrease in mean HbA1c in Caucasians over the 6-month
      evaluation period. 

PMID- 24121862
TI  - Failure to rescue as the conceptual basis for nursing clinical peer review.
AB  - It is incumbent for health care professionals to identify and reduce risk of
      harm. Left unchecked, minor risk may progress to increased care needs and
      subsequent morbidity. Recognizing nursing's front-line impact, a nursing clinical
      peer review committee was developed in an acute care hospital to analyze
      retrospectively select patient cases for opportunities to reduce risk in future
      similar situations. Risk-adjusted mortality and code blue calls decreased. 

PMID- 24121863
TI  - Memories of attachment hamper EEG cortical connectivity  in dissociative
      patients.
AB  - In this study, we evaluated cortical connectivity modifications by
      electroencephalography (EEG) lagged coherence analysis, in subjects with
      dissociative disorders and in controls, after retrieval of attachment memories.
      We asked thirteen patients with dissociative disorders and thirteen age- and sex
      matched healthy controls to retrieve personal attachment-related autobiographical
      memories through adult attachment interviews (AAI). EEG was recorded in the
      closed eyes resting state before and after the AAI. EEG lagged coherence before
      and after AAI was compared in all subjects. In the control group, memories of
      attachment promoted a widespread increase in EEG connectivity, in particular in
      the high-frequency EEG bands. Compared to controls, dissociative patients did not
      show an increase in EEG connectivity after the AAI. Conclusions: These results
      shed light on the neurophysiology of the disintegrative effect of retrieval of
      traumatic attachment memories in dissociative patients.

PMID- 24121864
TI  - Auditory spatial negative priming: what is remembered of irrelevant sounds and
      their locations?
AB  - The categorization and identification of previously ignored visual or auditory
      stimuli is typically slowed down--a phenomenon that has been called the negative
      priming effect and can be explained by the episodic retrieval of response
      inadequate prime information and/or an inhibitory model. A similar after-effect
      has been found in visuospatial tasks: participants are slowed down in localizing
      a visual stimulus that appears at a previously ignored location. In the auditory
      modality, however, such an after-effect of ignoring a sound at a specific
      location has never been reported. Instead, participants are impaired in their
      localization performance when the sound at the previously ignored location
      changes identity, a finding which is compatible with the so-called feature
      mismatch hypothesis. Here, we describe the properties of auditory spatial in
      contrast to visuospatial negative priming and report two experiments that specify
      the nature of this auditory after-effect. Experiment 1 shows that the detection
      of identity-location mismatches is a genuinely auditory phenomenon that can be
      replicated even when the sound sources are invisible. Experiment 2 reveals that
      the detection of sound-identity mismatches in the probe depends on the processing
      demands in the prime. This finding implies that the localization of irrelevant
      sound sources is not the inevitable consequence of processing the auditory prime
      scenario but depends on the difficulty of the target search process among
      distractor sounds.

PMID- 24121865
TI  - Encapsulation of mixtures of tuna oil, tributyrin and resveratrol in a spray
      dried powder formulation.
AB  - Spray dried emulsions are effective for carrying and stabilising combinations of
      fish oil and tributyrin, fish oil and resveratrol, or fish oil, tributyrin and
      resveratrol in one formulation. The encapsulation efficiencies were >99% for all
      three bioactives when a heated mixture of sodium caseinate: glucose: dried
      glucose syrup matrix (Encapsulant matrix 1) was used. When a heated sodium
      caseinate: glucose: processed starch matrix (Encapsulant matrix 2) was used, the
      encapsulation efficiencies were 90-92% for tributyrin and approximately 98% for
      resveratrol for all formulations but 79-91% for tuna oil where the efficiency was
      more formulation dependent. There was 84-86% remaining EPA, 85-87% remaining DHA,
      85% remaining tributyrin and 94-96% remaining resveratrol after 18 months at 25 
      degrees C storage of the spray dried emulsions using Encapsulant matrix 1 across
      all formulations. In comparison, there was 83-87% remaining EPA and 84-89%
      remaining DHA, 80-82% remaining tributyrin, and 81-100% remaining resveratrol
      across all formulations with Encapsulant matrix 2. In vitro studies showed that
      on sequential exposure to simulated gastric and intestinal fluids, <5% tuna oil
      was found as triglycerides, but all the tributyrin had been lipolysed. The
      presence of diglycerides, monoglycerides and free fatty acids in the in vitro
      digests suggested that lipolysis of tuna oil had occurred. The type of matrix
      used for encapsulating the bioactives had little effect on the lipolysis of the
      oils but affected the amount of solvent extractable resveratrol. The ability of
      delivering mixtures of bioactives within one formulation was demonstrated.

PMID- 24121866
TI  - Combined gene cluster engineering and precursor feeding to improve gougerotin
      production in Streptomyces graminearus.
AB  - Gougerotin is a peptidyl nucleoside antibiotic produced by Streptomyces
      graminearus . It is a specific inhibitor of protein synthesis and exhibits a
      broad spectrum of biological activities. Generation of an overproducing strain is
      crucial for the scale-up production of gougerotin. In this study, the natural and
      engineered gougerotin gene clusters were reassembled into an integrative plasmid
      by lambda-red-mediated recombination technology combined with classic cloning
      methods. The resulting plasmids pGOU and pGOUe were introduced into S.
      graminearus to obtain recombinant strains Sgr-GOU and Sgr-GOUe, respectively.
      Compared with the wild-type strain, Sgr-GOU led to a maximum 1.3-fold increase in
      gougerotin production, while Sgr-GOUe resulted in a maximum 2.1-fold increase in
      gougerotin production. To further increase the yield of gougerotin, the effect of
      different precursors on its production was investigated. All precursors,
      including cytosine, serine, and glycine, had stimulatory effect on gougerotin
      production. The maximum gougerotin yield was achieved with Sgr-GOUe in the
      presence of glycine, and it was approximately 2.5-fold higher than that of the
      wild-type strain. The strategies used in this study can be extended to other
      Streptomyces for improving production of industrial important antibiotics.

PMID- 24121867
TI  - Cloning and characterization of a novel acidic cutinase  from Sirococcus
      conigenus.
AB  - A cutinase gene (ScCut1) was amplified by PCR from the genomic DNA of the
      ascomycetous plant pathogen Sirococcous conigenus VTT D-04989 using degenerate
      primers designed on the basis of conserved segments of known cutinases and
      cutinase-like enzymes. No introns or N- or O-glycosylation sites could be
      detected by analysis of the ScCut1 gene sequence. The alignment of ScCut1 with
      other fungal cutinases indicated that ScCut1 contained the conserved motif G-Y-S
      Q-G surrounding the active site serine as well as the aspartic acid and histidine
      residues of the cutinase active site. The gene was expressed in Pichia pastoris,
      and the recombinantly produced ScCut1 enzyme was purified to homogeneity by
      immobilized metal affinity chromatography exploiting a C-terminal His-tag
      translationally fused to the protein. The purified ScCut1 exhibited activity at
      acidic pH. The K(m) and V(max) values determined for pNP-butyrate esterase
      activity at pH 4.5 were 1.7 mM and 740 nkat mg-1, respectively. Maximal
      activities were determined at between pH 4.7 and 5.2 and at between pH 4.1 and
      4.6 with pNP-butyrate and tritiated cutin as the substrates, respectively. With
      both substrates, the enzyme was active over a broad pH range (between pH 3.0 and
      7.5). Activity could still be detected at pH 3.0 both with tritiated cutin and
      with p-nitrophenyl butyrate (relative activity of 25 %) as the substrates. ScCut1
      showed activity towards shorter (C2 to C3) fatty acid esters of p-nitrophenol
      than towards longer ones. Circular dichroism analysis suggested that the
      denaturation of ScCut1 by heating the protein sample to 80  degrees C was to a
      great extent reversible.

PMID- 24121869
TI  - Convenient metal embedment into mesoporous silica channels for high catalytic
      performance in AB dehydrogenation.
AB  - The infiltration of palladium nanoparticles (PdNPs) into the channels of SBA-15
      was conveniently achieved via an incipient wetness procedure employing a
      tetraglyme solution. Electron tomography demonstrated that PdNPs were outgrown
      preferentially from the channels. The resultant Pd/SBA-15 showed high performance
      in the dehydrogenation kinetics of ammonia borane. 

PMID- 24121870
TI  - Trialogue Plus: Management of cardiovascular risk in  hyperglycaemic/diabetic
      patients at hospital discharge.
AB  - Diabetes mellitus and hyperglycaemia are both independent risk factors (RF) for
      cardiovascular (CV) events and increased general and CV mortality. Type 2
      diabetes, which is often associated with obesity, hypertension and dyslipidaemia,
      is accompanied by an up to fourfold increase in the incidence of acute coronary
      heart disease compared to normoglycaemia, even when other CV RF are equal. In the
      diabetic population, acute CV events are more likely to have associated cardiac
      complications, such as heart failure, and CV mortality is increased by twofold
      fourfold. Several patients, hospitalised in medical, cardiology and intensive
      care departments, have undiagnosed diabetes mellitus or elevated glucose levels
      at the time of admission. These conditions require intensive care in the acute
      phase and dedicated follow-up at discharge. The Trialogue Plus project was
      created with the goal of providing good clinical practice guidelines and
      recommendations for the management of CV risk in patients with
      diabetes/hyperglycaemia at discharge from hospital. The aim is developing a
      document that defines timing, diagnostics, targets and therapeutic strategy for
      the management of CV risk, both in primary and in secondary prevention of
      patients with diabetes/hyperglycaemia who have experienced an event, involving
      the Diabetologist, Cardiologist, Internist, GP and area Specialists. This
      document concerns the implementation of existing guidelines and consensus
      statements, and as such, the recommendations have not been classified on the
      basis of scientific evidence and strength.

PMID- 24121871
TI  - St. John's wort extract and hyperforin protect rat and human pancreatic islets
      against cytokine toxicity.
AB  - The extract of Hypericum perforatum (St. John's wort, SJW) and its component
      hyperforin (HPF) were previously shown to inhibit cytokine-induced activation of
      signal transducer and activator of transcription-1 and nuclear factor kappaB and
      prevent apoptosis in a cultured beta-cell line. Objective of this study was to
      assess the protection exerted by SJW and HPF on isolated rat and human islets
      exposed to cytokines in vitro. Functional, ultrastructural, biomolecular and cell
      death evaluation studies were performed. In both rat and human islets, SJW and
      HPF counteracted cytokine-induced functional impairment and down-regulated mRNA
      expression of pro-inflammatory target genes, such as iNOS, CXCL9, CXCL10, COX2.
      Cytokine-induced NO production from cultured islets, evaluated by nitrites
      measurement in the medium, was significantly reduced in the presence of the
      vegetal compounds. Noteworthy, the increase in apoptosis and necrosis following
      48-h exposure to cytokines was fully prevented by SJW and partially by HPF.
      Ultrastructural morphometric analysis in human islets exposed to cytokines for 20
      h showed that SJW or HPF avoided early beta-cell damage (e.g., mitochondrial
      alterations and loss of insulin granules). In conclusion, SJW compounds protect
      rat and human islets against cytokine effects by counteracting key mechanisms of
      cytokine-mediated beta-cell injury and represent promising pharmacological tools
      for prevention or limitation of beta-cell dysfunction and loss in type 1
      diabetes.

PMID- 24121872
TI  - Assessment of an educational intervention in the management of non-critical
      inpatient glycemic control.
AB  - In hospitalized diabetic patients, the recommended insulin therapy is basal bolus
      plus correction-dose regimen instead of sliding-scale insulin. The purpose of
      this study was to evaluate the effect of the implementation of a new protocol
      based on basal bolus therapy on managing diabetes in a university hospital
      setting. We performed a cross-sectional study before and 12 months after a 4
      month intervention period to implement a basal bolus regimen in hospitalized
      patients. Non-critical patients admitted into the hospital for at least 72 h were
      included. Changes in prescribing habits, glucose control and incidence of
      hypoglycemia were evaluated. An increase in the use of the new protocol and a
      decrease in sliding scale were observed after the intervention. In the pre
      intervention group, a total of 59.2% glucose readings were between 70 and 180
      mg/dL versus 57.1% after the intervention, without observing statistical
      differences. Significant reductions in hypoglycemia between pre- and post
      intervention (13.04 vs. 4.08%, p = 0.0215) were observed. The percentage of
      hospitalized diabetic patients who had HbA1c was 10.43 and 4.08% in pre- and post
      intervention phases, respectively. The protocol showed beneficial outcomes in
      terms of fewer hypoglycemia episodes and reflected a change in prescription
      habits, but it did not improve glycemic control. Furthermore, the percentage of
      patients who had an HbA1c test during their hospitalization remained very low
      after the intervention. This fact may seriously limit the correct management of
      hyperglycemia after the hospital discharge.

PMID- 24121873
TI  - Biomimetic design and fabrication of porous chitosan-gelatin liver scaffolds with
      hierarchical channel network.
AB  - The presence of a hierarchical channel network in tissue engineering scaffold is
      essential to construct metabolically demanding liver tissue with thick and
      complex structures. In this research, chitosan-gelatin (C/G) scaffolds with fine
      three-dimensional channels were fabricated using indirect solid freeform
      fabrication and freeze-drying techniques. Fabrication processes were studied to
      create predesigned hierarchical channel network inside C/G scaffolds and achieve
      desired porous structure. Static in-vitro cell culture test showed that HepG2
      cells attached on both micro-pores and micro-channels in C/G scaffolds
      successfully. HepG2 proliferated at much higher rates on C/G scaffolds with
      channel network, compared with those without channels. This approach demonstrated
      a promising way to engineer liver scaffolds with hierarchical channel network,
      and may lead to the development of thick and complex liver tissue equivalent in
      the future.

PMID- 24121874
TI  - A Venturi effect can help cure our trees.
AB  - In woody plants, xylem sap moves upwards through the vessels due to a decreasing
      gradient of water potential from the groundwater to the foliage. According to
      these factors and their dynamics, small amounts of sap-compatible liquids (i.e.
      pesticides) can be injected into the xylem system, reaching their target from
      inside. This endotherapic method, called "trunk injection" or "trunk infusion"
      (depending on whether the user supplies an external pressure or not), confines
      the applied chemicals only within the target tree, thereby making it particularly
      useful in urban situations. The main factors limiting wider use of the
      traditional drilling methods are related to negative side effects of the holes
      that must be drilled around the trunk circumference in order to gain access to
      the xylem vessels beneath the bark. The University of Padova (Italy) recently
      developed a manual, drill-free instrument with a small, perforated blade that
      enters the trunk by separating the woody fibers with minimal friction.
      Furthermore, the lenticular shaped blade reduces the vessels' cross section,
      increasing sap velocity and allowing the natural uptake of an external liquid up
      to the leaves, when transpiration rate is substantial. Ports partially close soon
      after the removal of the blade due to the natural elasticity and turgidity of the
      plant tissues, and the cambial activity completes the healing process in few
      weeks. 

PMID- 24121876
TI  - [Medicinal therapy and course control of glaucoma.]

PMID- 24121875
TI  - Mechanical testing of different knot types using high-performance suture
      material.
AB  - PURPOSE: This laboratory study aimed to evaluate the loop security, knot
      security, cyclic loading resistance and load-to-failure rate of three different
      knot types with establishing a new experimental set-up. Additionally, the mode of
      failure of each knot was evaluated. METHODS: With the use of nonabsorbable,
      braided polyethylene sutures, USP size No. 2 [Hi-Fi(r); ConMed Linvatec], the
      arthroscopic knot types Dines, SMC as well as the surgeon's knot were tested
      using a material testing machine. The knots were tied openly as well as
      arthroscopically. The set-up enables testing of knot configurations while
      eliminating friction between knot loop and its suspension points. Including all
      test procedures, a total of 216 knots were tested. RESULTS: All openly tied knot
      types and ten of each type of arthroscopically tied knots resisted against cyclic
      loading of 1,000 cycles. With subsequent load-to-failure testing, openly tied
      knot types achieved significantly higher values of tensile strength than
      arthroscopically tied knots. Regarding clinical failure, defined as an elongation
      of 3 mm, Dines knot reached highest loop as well as knot security. Knot slippage
      was the most common failure mechanism at an elongation of 3 mm, whereas suture
      breakage was evaluated most at an elongation of 6 mm. CONCLUSIONS: The new
      experimental set-up confirms the loop security of arthroscopic knot types. Using
      a knot pusher clinically is a key factor to attain this as compared to openly
      hand-tied techniques. The Dines knot presented the highest reliability. It may
      provide a secure tissue healing during rehabilitation and consequently can be
      recommended for clinical application.

PMID- 24121877
TI  - [Wide-field fundus autofluorescence in non-infectious posterior uveitis].
AB  - BACKGROUND: Posterior uveitis comprises a heterogeneous group of diseases with
      inflammatory alterations of the posterior fundus and is a common cause of visual
      impairment and blindness. The goal of this study was to evaluate the diagnostic
      value of wide-field fundus autofluorescence (FAF) in patients with non-infectious
      posterior uveitis and chorioretinal alterations. MATERIAL AND METHODS: In this
      study 73 eyes from 51 patients were included. Best-corrected visual acuity, wide
      field color and FAF images achieved by a wide-field scanning laser
      opththalmoscope (SLO, Optomap P200Tx, Optos PLC, Dunfermline UK) and a full
      ophthalmological examination were obtained from each patient. A systematic
      analysis of chorioretinal alterations detected with FAF and color images was
      conducted followed by the evaluation of the diagnostic information of wide-field
      FAF compared to the clinical finding and wide-field color images. RESULTS: Of the
      73 eyes included in the study 52 showed peripheral alterations. In 32 cases wide
      field FAF images revealed a greater number and more extensive chorioretinal
      alterations than the corresponding wide-field color images of the posterior
      fundus. CONCLUSIONS: In this study wide-field FAF images showed more
      chorioretinal alterations than seen in funduscopy or in color SLO images.
      Therefore, wide-field FAF images offer important additional information for
      detection and documentation of peripheral and central chorioretinal alterations.

PMID- 24121878
TI  - [Hypertensive changes of the fundus].
AB  - Systemic hypertension affects approximately 25 % of the population worldwide and
      is the most important preventable risk factor for cardiovascular diseases.
      Hypertension-related fundus abnormalities can be classified into hypertensive
      retinopathy, choroidopathy, and optic neuropathy. Hypertensive retinopathy causes
      vascular constriction of retinal arterioles and typical fundus findings, such as
      blot hemorrhages, hard exudates and cotton wool spots resulting from ischemia
      within the nerve fiber layer. The use of a detailed grading system based on the
      severity of vascular constriction is not practicable as arteriosclerotic changes
      are common among elderly people. Therefore, early stages with pure vascular
      pathology should be differentiated from severe forms of hypertensive retinopathy
      with parenchymal changes of the fundus. Screening the retina for hypertensive
      changes is essential in cases of severe systemic hypertension, acute visual
      impairment, diabetes mellitus and pregnancy.

PMID- 24121879
TI  - Outcome in patients with resectable locally recurrent rectal cancer after total
      mesorectal excision with and without previous neoadjuvant radiotherapy for the
      primary rectal tumor.
AB  - BACKGROUND: The widespread use of neoadjuvant radiotherapy (nRTx) followed by
      total mesorectal excision (TME) introduced the problem of treating locally
      recurrent rectal cancer (LRRC) after nRTx and TME. Few data exist on the outcome
      of the surgical treatment of this type of LRRC and the influence of nRTx for the
      primary tumor on the outcome is unclear. METHODS: All patients receiving
      multimodality treatment (including intraoperative radiotherapy) for LRRC in our
      center between 1996 and 2012 were analyzed retrospectively. The outcome of
      patients with nonmetastasized resectable LRRC who received nRTx and TME for the
      primary tumor was compared to the outcome of patients who did not receive nRTx
      for the primary tumor. RESULTS: During this period, 139 patients underwent
      surgery for LRRC; 93 of these patients underwent curative surgery for LRRC after
      TME for the primary tumor. Sixty-five patients did not receive nRTx for the
      primary tumor, whereas 28 patients received nRTx for the primary tumor. There
      were no significant differences in the number of incomplete resections or
      perioperative morbidities. There was no significant difference in 5-year overall
      survival (28 vs. 43%, p = 0.81), recurrence-free survival (55 vs. 48%, p = 0.5),
      and disease-free survival (27 vs. 40%, p = 0.59). CONCLUSIONS: Surgical treatment
      of carefully selected patients with nonmetastasized resectable LRRC after nRTx
      and TME for the primary tumor is feasible and can result in sustained local
      control and overall survival. Patients with resectable LRRC who received nRTx for
      the primary tumor do not have a poorer outcome than patients who did not.

PMID- 24121880
TI  - Reconsideration of the indications for adjuvant chemotherapy for liver metastases
      from colorectal cancer after initial hepatectomy.
AB  - BACKGROUND: The effectiveness of perioperative adjuvant chemotherapy for
      colorectal cancer liver metastasis (CRLM) remains a matter of debate. Despite the
      lack of clear evidence supporting its effectiveness after curative hepatectomy,
      adjuvant chemotherapy has been widely used clinically. The purpose of this study
      was to clarify the indications for adjuvant chemotherapy in order to develop an
      appropriate treatment strategy for CRLM. METHODS: The clinicopathological factors
      of 110 patients who underwent initial hepatectomy for CRLM between April 2000 and
      March 2010 were retrospectively analyzed. The prognostic factors of CRLM were
      identified and then CRLM was stratified according to the number of prognostic
      factors into the high-score group (H-group: score 2 or 3) and the low-score group
      (L-group: score 0 or 1), and the effectiveness of adjuvant chemotherapy was
      analyzed in each group. RESULTS: Multivariate analysis identified pT4 (p =
      0.0047), lymph node metastasis in colorectal cancer (CRC) (p = 0.0165), and H2
      classification (p = 0.0051) as factors related to a poor prognosis. The overall 5
      year survival rate was markedly higher in the L-group (68 %) than in the H-group
      (26 %, p < 0.0001). Moreover, in the L-group, patients who did not receive
      adjuvant chemotherapy had the same prognosis as those who received adjuvant
      chemotherapy. As for recurrence, tumor relapse more often was treated by
      resection in the L-group than in the H-group (p = 0.0339). CONCLUSIONS: Adjuvant
      chemotherapy did not improve overall survival and disease-free survival in
      patients with no more than two factors of the H2-classification, invasion depth
      pT4, and lymph node metastasis in CRC.

PMID- 24121881
TI  - Tumescent technique does not increase the risk of complication following
      mastectomy with immediate reconstruction.
AB  - BACKGROUND: Despite the growing interest in the advantages of tumescent
      mastectomy technique, there remain concerns that tumescent solution may increase
      postoperative complication rates. This study evaluates patient outcomes following
      tumescent mastectomy in the setting of immediate prosthetic reconstruction.
      METHODS: Retrospective review of 1,491 breasts (1,030 patients) treated by 4
      oncologic and 2 reconstructive surgeons between 2004 and 2012 at a single
      institution. The primary outcomes of interest included seroma, hematoma,
      infection, and mastectomy flap necrosis, as well as conversion to autologous
      reconstruction. Multiple logistic regression was used to determine the adjusted
      influence of tumescence on outcomes. RESULTS: The tumescent cohort (n = 890
      breasts) was younger and experienced lower rates of preoperative radiation than
      the nontumescent cohort (n = 601 breasts). Mean follow-up was 21.2 months. While
      tumescent procedures were on average 20 min faster, postoperative complication
      rates did not significantly differ between cohorts. Regression analysis
      controlling for potential confounders, including differences in surgeon
      technique, failed to identify tumescent mastectomy as an independent risk factor
      for complication [odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.8-1.8,
      p = 0.385]. Individually, neither seroma, hematoma, infection, nor flap necrosis
      was affected significantly by the use of tumescence (OR = 1.66, 95% CI = 0.73
      3.78, p = 0.229; OR = 1.11, 95% CI = 0.42-2.95, p = 0.837; OR = 0.84, 95% CI =
      0.4-1.75, p = 0.689; OR = 1.19, 95% CI = 0.7-2.03, p = 0.67, respectively).
      DISCUSSION: This longitudinal study is well equipped to assess the influence of
      tumescent mastectomy technique in the hands of experienced and high-volume
      oncologic surgeons on postoperative outcomes. Our analysis suggests that in the
      setting of an immediate prosthetic reconstruction, tumescent mastectomy does not
      independently affect postoperative complication rates.

PMID- 24121882
TI  - Systemic therapy for patients with resectable hepatic colorectal metastases:
      improving patient selection.

PMID- 24121884
TI  - Does anti-HBV therapy benefit the prognosis of HBV-related hepatocellular
      carcinoma following hepatectomy?
AB  - The Hepatitis B virus (HBV) is an important etiological factor for
      hepatocarcinogenesis, because HBV DNA load and HBV reactivation are major risks
      that influence the long-term survival of hepatocellular carcinoma (HCC) patients
      who underwent hepatectomy and, thus, may cause postoperative liver function
      deterioration, tumor recurrence, and reduce patient's overall survival. However,
      anti-HBV therapy can suppress HBV replication, improve the remnant liver
      function, render patients better able to tolerate HCC treatments, and may even
      improve their prognosis. In this paper, an anti-HBV therapy that benefits the
      prognosis of HBV-related HCC following hepatectomy is reviewed.

PMID- 24121883
TI  - Clark level risk stratifies patients with mitogenic thin melanomas for sentinel
      lymph node biopsy.
AB  - BACKGROUND: The role for sentinel lymph node biopsy (SLNB) in patients with thin
      melanoma (<=1 mm) remains controversial. We examined a large cohort of patients
      with thin melanoma to better define predictors of SLN positivity. METHODS: From
      1995 to 2011, 781 patients with thin primary melanoma and evaluable
      clinicopathologic data underwent SLNB at our institution. Predictors of SLN
      positivity were determined using univariate and multivariate regression analyses,
      and patients were risk-stratified using a classification and regression tree
      (CART) analysis. RESULTS: In the study cohort (n = 781), 29 patients (3.7%) had
      nodal metastases. In the univariate analysis, mitotic rate [odds ratio (OR) =
      8.11, p = 0.005], Clark level (OR 4.04, p = 0.003), and thickness (OR 3.33, p =
      0.011) were significantly associated with SLN positivity. In the multivariate
      analysis, MR (OR 7.01) and level IV-V (OR 3.45) remained significant predictors
      of SLN positivity. CART analysis initially stratified lesions by mitotic rate;
      nonmitogenic lesions (n = 273) had a 0.7% SLN positivity rate versus 5.6% in
      mitogenic lesions (n = 425). Mitogenic lesions were further stratified by Clark
      level; patients with level II-III had a 2.9% SLN positivity rate (n = 205) versus
      8.2% with level IV-V (n = 220). With median follow-up of 6.3 years, five SLN
      negative patients developed nodal recurrence and four SLN-positive patients died
      of disease. CONCLUSIONS: SLN positivity is low in patients with thin melanoma
      (3.7%) and exceedingly so in nonmitogenic lesions (0.7%). Appreciable rates of
      SLN positivity can be identified in patients with mitogenic lesions, particularly
      with concurrent level IV-V regardless of thickness. These factors may guide
      appropriate selection of patients with thin melanoma for SLNB.

PMID- 24121885
TI  - [The AIDA STEMI study].

PMID- 24121886
TI  - [The FAME 2 study].

PMID- 24121888
TI  - [Intensive or palliative treatment in end-stage patients].

PMID- 24121887
TI  - [The CHAMPION PHOENIX study].

PMID- 24121889
TI  - [Intracardiac echography in interventional cardiology].
AB  - Since its early development, interventional cardiology relies on radiological
      imaging to show and describe vascular structures involved in percutaneous
      treatment. However, the development of the transcatheter approach to structural
      heart disease has highlighted the limits of X-rays in guiding interventions
      targeting soft heart tissues because of their low radiological resolution.
      Transesophageal echocardiography has thus gained an important role in many
      catheterization laboratories that perform percutaneous structural heart disease
      interventions. The endorsement of this technique necessarily requires expertise
      of echocardiographers and anesthesiologists for endotracheal intubation, thus
      increasing the logistic complexity of the procedure. Hence, the idea to apply
      ultrasonography directly into the heart, thus the introduction of intracardiac
      echography. At present, there are two different technological implementations of
      intracardiac echography related to the use of an electronic or mechanical
      ultrasonic transducer placed at the tip of a catheter inserted into the cardiac
      chambers, most frequently via femoral venous vascular access. In this review, we
      describe the potentials, advantages and limits of intracardiac echography, as
      well as its operative function, current use, and future developments. 

PMID- 24121890
TI  - [What cardiologists should know to manage acute complications in mechanical
      circulatory support recipients].
AB  - Patients with advanced heart failure refractory to optimal medical treatment have
      a high mortality and a poor quality of life with frequent hospital admissions.
      The lack of alternative treatment options has prompted the development of
      mechanical circulatory support (MCS) devices, first as bridge to heart transplant
      and subsequently as destination therapy as a valid alternative to transplant.
      Last generation MCS devices are mechanically reliable and their management has
      become increasingly less complex. Nowadays, medium-term survival does not
      significantly differ between MCS and heart transplant recipients. MCS management
      programs require a multidisciplinary team to optimize the pathway leading to
      rehabilitation and improved quality of life and decrease the frequent occurrence
      of complications. However, in the near future with the growing number of
      implants, the chances for clinical cardiologists to come across a MCS recipient
      will increase. The management of general or acute problems will no longer be
      limited to tertiary implanting centers. A key issue to improve patient outcomes
      is the provision of a smooth and careful transition from the hospital environment
      to home care. The aim of this review is to start this process by providing basic
      notions and general indications through several scenarios of MCS recipients
      presenting to the emergency room for acute clinical problems. 

PMID- 24121891
TI  - [Primary angioplasty in a patient with acute inferior myocardial infarction: the
      unexpected trap].
AB  - We report a case of acute inferior myocardial infarction caused by occlusion of
      an anomalous right coronary artery, successfully treated with primary
      angioplasty. When an anomalous origin of a coronary artery is suspected, it is
      crucial to perform aortic angiography or left ventriculography in multiple
      projections. 

PMID- 24121892
TI  - [A rare case of giant coronary aneurysms involving both coronary arteries:
      computed tomographic-angiographic findings].
AB  - We describe the case of a patient evaluated for the incidental finding of a
      suspected paracardiac mass. A computed tomography examination demonstrated two
      giant coronary aneurysms, containing endoluminal thrombi, involving both coronary
      arteries. Coronary angiography confirmed the diagnosis. The patient underwent
      surgical treatment because of the high risk of spontaneous rupture of the masses,
      owing to the early compressive effect especially on the right ventricular free
      wall. 

PMID- 24121893
TI  - [A multi-device approach to an unusual case of left main thrombosis: when manual
      thrombectomy is not enough].
AB  - We report an unusual case of left main thrombosis with distal embolization in the
      left anterior descending coronary artery (LAD). Two filter wires were placed in
      both LAD and circumflex coronary arteries at the beginning of the procedure.
      Manual thrombectomy was performed but only a portion of the left main thrombosis
      was removed; residual debris was displaced into the distal LAD but captured by
      the filter. A loco-regional infusion of abciximab was finally administered by a
      microporous balloon in order to treat residual embolization in the distal LAD.
      This case shows that manual thrombectomy does not always allow for complete and
      safe removal of thrombotic material, especially when high-burden coronary
      thrombosis occurs in large, proximal vessels. A multi-device approach has proved
      useful in this patient, allowing to obtain complete resolution of luminal
      thrombosis. 

PMID- 24121894
TI  - [SICI-GISE position paper on drug-coated balloon use in the coronary district].
AB  - Drug-coated balloons are a new tool for the treatment of patients with coronary
      artery disease. The main feature of this technology is a rapid and homogeneous
      transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the
      time of balloon inflation, when neointimal proliferation, in response to
      angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive
      advantages over stents: the absence of permanent scaffold and polymer, the
      respect of the original coronary anatomy, and limited inflammatory stimuli,
      thereby allowing for short-term dual antiplatelet therapy. At present, a variety
      of devices are available in the market, with limited scientific data for the vast
      majority of them. Thus, the Italian Society of Interventional Cardiology (SICI
      GISE) decided to coordinate the efforts of a group of renowned experts in this
      field, in order to produce a position paper on the correct use of drug-coated
      balloons in all settings of coronary artery disease, giving a class of indication
      to each one, based on clinical evidence. This position paper represents a quick
      reference for operators, investigators and manufacturers to promote the
      understanding and the correct use of the drug-coated balloon technology in
      everyday clinical practice. 

PMID- 24121895
TI  - [SICI-GISE position paper on the requirements for diagnostic and interventional
      procedures in patients with peripheral arterial disease].
AB  - Interventional procedures on peripheral vessels are the field of a novel
      specialty dedicated to the diagnosis and minimally invasive endovascular
      treatment of diseases involving the cerebral, thoracic and abdominal arteries
      (including renal and visceral arteries), as well as the peripheral arteries
      (femoro-popliteal arteries and the arteries below the knee). At present,
      physicians with three different types of medical training, each involving
      particular strengths and characteristics, specialize in endovascular treatment of
      patients with peripheral arterial disease: vascular surgeons, interventional
      radiologists and interventional cardiologists. Treatment of high-risk patients in
      terms of anatomical and clinical (serious comorbidities) complexity raised the
      need for the interventional cardiologist to face issues related to technical
      aspects of the procedure, multilevel pathology management and adequate
      indication. To achieve this goal, interventional cardiologists require particular
      facilities and clinical skills. The objectives of this position paper from the
      Italian Society of Interventional Cardiology (SICI-GISE) are (i) to define the
      theoretical background and practical training required to ensure that
      interventional cardiologists maintain high-quality standards also in the field of
      treatment of peripheral arterial disease, by establishing shared rules and
      drafting papers; (ii) to standardize the procedures of interventional cardiology
      operational units that treat patients with peripheral arterial disease in Italy
      on the basis of scientific evidence, and (iii) to establish common requirements
      in terms of facilities and regulations. 

PMID- 24121898
TI  - Comparative evaluations of reward dimensions in honey bees:  evidence from two
      alternative forced choice proboscis-extension  conditioning.
AB  - A major challenge in understanding choice behaviour is determining how subjects
      evaluate alternatives that differ along multiple dimensions. Of particular
      interest is whether similar dimensions are compared to each other or whether each
      alternative is assigned an absolute value (utility). We assumed that choice
      proportions would follow Weber's effect, according to which discrimination is
      proportional to relative difference (difference/mean). We tested honey bees in a
      two-alternative forced choice (2AFC) paradigm of proboscis-extension response
      (PER) conditioning. Subjects were conditioned over six trials to associate each
      of two odours with sucrose solution rewards and then tested in a choice trial
      between the two alternatives. Each group of subjects was tested in one treatment,
      and there were four treatments in each of six experiments. Rewards differed in
      delay, duration of feeding, and sucrose concentration. In each treatment, the
      high-profitability alternative was better than the low-profitability alternative
      along a single dimension, but between treatments of each experiment values in
      another dimension monotonically increased. Proboscis-response proportions during
      the conditioning phase tended to be greater for the high-profitability
      alternative, and choice proportions for it in the choice phase ranged between
      0.72 and 0.89 in the 24 treatments. We show for the first time that harnessed
      bees are sensitive to reward delay. Preferences did not differ statistically
      between the different treatments of any of the experiments. The results support
      comparative evaluation of alternatives and are pertinent to multi-attribute
      choice, with implications for context-dependent preferences. We also discuss the
      potential advantages of the 2AFC PER simultaneous choice assay.

PMID- 24121896
TI  - [Multidisciplinary position paper on the management of patent foramen ovale in
      the presence of cryptogenic cerebral ischemia - Italian version 2013].
AB  - There is no generally accepted consensus on the management of patent foramen
      ovale (PFO) in the presence of cryptogenic cerebral ischemia, because of the lack
      of conclusive evidence. The aim of this position paper was to develop and promote
      a joint approach based on available data that may be shared by different
      specialists, while waiting for definite results from randomized controlled
      trials. A position statement was produced involving the major national scientific
      societies. The task force members were nominated by the presidents and/or
      executive boards of each society or working group, as appropriate, based on their
      previous work in relevant topic areas. Specific task force working groups
      prepared the drafts. In order to achieve maximum agreement, these drafts were
      merged and distributed to the scientific societies for local evaluation. The
      ensuing final draft, merging all the revisions, was reviewed by the task force
      and finally approved by all scientific societies. The following issues were
      addressed: definitions of transient ischemic attack (TIA) and both symptomatic
      and asymptomatic cryptogenic stroke; formulation of a diagnostic workup for
      patients with clinical event(s) and PFO; recommendations regarding medical and
      interventional treatment options considering individual risk factors based on the
      three available randomized trials and other observational studies;
      recommendations regarding requirements for operators and centers in Italy;
      definition of a follow-up evaluation protocol. In conclusion, available data
      provided the basis for the first multi-society position paper on the management
      of cryptogenic stroke/TIA and PFO. 

PMID- 24121899
TI  - Microworms swallow the nanobait: the use of nanocoated microbial cells for the
      direct delivery of nanoparticles into Caenorhabditis elegans.
AB  - The application of in vivo models in assessing the toxicity of nanomaterials is
      currently regarded as a promising way to investigate the effects of nanomaterials
      on living organisms. In this paper we introduce a novel method to deliver
      nanomaterials into Caenorhabditis elegans nematodes. Our approach is based on
      using nanoparticle-coated microbial cells as "nanobait", which are ingested by
      nematodes as a sole food source. We found that nematodes feed on the nanocoated
      bacteria (Escherichia coli) and microalgae (Chlorella pyrenoidosa) ingesting them
      via pharyngeal pumping, which results in localization of nanoparticles inside the
      digestive tract of the worms. Nanoparticles were detected exclusively inside the
      intestine, indicating the efficient delivery based on microbial cells. Delivery
      of iron oxide nanoparticles results in magnetic labelling of living nematodes,
      rendering them magnetically-responsive. The use of cell-mediated delivery of
      nanoparticles can be applied to investigate the toxicity of polymer-coated
      magnetic nanoparticles and citrate-capped silver nanoparticles in Caenorhabditis
      elegans in vivo. 

PMID- 24121900
TI  - Idiopathic intracranial hypertension in a child with obstructive sleep apnea
      cured by tonsillectomy/adenoidectomy.

PMID- 24121901
TI  - Enhanced photosensitized activity of a BiOCl-Bi2WO6 heterojunction by effective
      interfacial charge transfer.
AB  - A BiOCl-Bi2WO6 heterojunction with a chemically bonded interface was synthesized
      via a facile one-step solvothermal method. A series of characterization
      techniques (XRD, XPS, TEM, SEM, EDS etc.) confirmed the existence of a BiOCl
      Bi2WO6 interface. The heterojunction yielded a higher photodegradation rate of
      Rhodamine B under visible light irradiation compared to its individual
      components. Theoretical studies based on density functional theory calculations
      indicated that the enhanced photosensitized degradation activity could be
      attributed to the favorable band offsets across the BiI-O-BiII bonded interface,
      leading to efficient interfacial charge carrier transfer. Our results reveal the
      photosensitized mechanism of BiOCl-Bi2WO6 heterojunctions and demonstrate their
      practical use as visible-light-driven photocatalytic materials. 

PMID- 24121902
TI  - Expression of hormonal receptors in osteosarcomas of the jaw bones: clinico
      pathological analysis of 21 cases.
AB  - BACKGROUND: Sexual hormones have an important role in many hormone-dependent
      tumors like breast and prostate carcinomas, and also a relationship has been
      found with bone metabolism and bone tumors. Some studies have demonstrated that
      the expression of hormonal receptors (HR) in osteosarcomas (OS) of long bones is
      associated with gender, histological grade, histological type, and a possibly may
      be connection with pathogenesis and evolution. However, to our knowledge there
      are no studies of HR in osteosarcomas of craniofacial bones (OS-CF). OBJECTIVE:
      To assess the expression of hormonal receptors in OS-CF. MATERIAL AND METHODS:
      Twenty one cases of OS-CF were included in this study. Clinical outcome was
      obtained from clinical charts. Histological sections were reviewed, and
      immunohistochemistry studies for estrogen, progesterone and androgen receptors
      were performed. RESULTS: A striking female predominance was found (2:1), with a
      median age of 35 years. The predominant type of OS was osteoblastic (52.4%), and
      histological grade was high in 86%. Follow-up was obtained in 13 cases and ranged
      from 6 to 118 months (median 29 months). There were 8 patients (61.5%) dead or
      alive with progressive disease in the last follow up. Negative expression of HR
      was found in 19/21 cases; one showed weak nuclear expression for estrogen
      receptor, and another for androgen receptor. Progesterone receptor was negative
      in all cases. CONCLUSIONS: OS-CF mostly affected females, most of them were of
      the osteoblastic type and of high grade. Hormonal expression was practically
      negative in osteosarcoma of craniofacial bones.

PMID- 24121903
TI  - Transoral, retromolar, para-tonsillar approach to the styloid process in 6
      patients with Eagle's syndrome.
AB  - OBJECTIVES: Eagle's syndrome is caused by an elongated or mineralised styloid
      process and characterised by facial and pharyngeal pain, odynophagia and
      dysphagia. Diagnosis is based on clinical findings. However radiologic imaging,
      like panoramic radiograph, helps to confirm the diagnosis. There are different
      treatments of the Eagle's syndrome. Anti-inflammatory medication (carbamazepime,
      corticosteroids) and/or surgical interventions are established. The aim of the
      different surgical techniques is to resect the elongated styloid process near the
      skull base. STUDY DESIGN: A transoral, retromolar, para-tonsillar approach was
      performed to expose and resect the elongated calcified styloid process in a
      consecutive series of six patients. The use of different angled ring curettes,
      generally used in hypophysis surgery, facilitated the preparation of the styloid
      process through the surrounding tissue to the skull base, without a compromise to
      the surrounding tissue. Clinical examinations were performed pre- and
      postoperatively (3 month and after 1 year after surgery) in all patients.
      RESULTS: No intra- or postoperative complications were observed. The hypophysis
      ring curettes facilitated the preparation of the styloid process to the skull
      base. CONCLUSIONS: The transoral, retromolar, para-tonsillar approach is a secure
      and fast method to resect an elongated symptomatic styloid process. Side effects
      of the classical transoral trans-tonsillar approach did not occur.

PMID- 24121904
TI  - Prenatal effects by exposing to amoxicillin on dental enamel in Wistar rats.
AB  - Amoxicillin is an antibiotic widely prescribed; its most frequent side effects
      are gastrointestinal disorders and hypersensitivity reactions. Over the last 10
      years studies have been published which suggest that amoxicillin may cause dental
      alterations similar to dental fluorosis. Never the less, the results are not
      conclusive, this is why it was planned the need to make controlled studies on
      test animals. OBJECTIVE: The purpose of this study was to determine the effect
      produced by amoxicillin prenatal administration on dental enamel in Wistar rats.
      STUDY DESIGN: 12 pregnant adult rats were used distributed into five different
      groups: witness control (n=2) didn't get any treatment; negative control (n=2)
      they were prescribed with saline solution; positive control (n=3) they were
      prescribed with tetracycline 130 mg/kg, and two groups (n=3 and n=2) treated with
      amoxicillin doses of 50 and 100 mg/kg respectively. The treatments were daily
      administered by mouth, from the 6th gestation day to the end of gestation. Twenty
      five days after they were born, the offspring were sacrificed with a sodium
      pentobarbital overdose, the mandible was dissected and the first lower molars
      were gotten. The samples were fixed in 10% formaldehyde solution and clinically
      and histologically observed to determine any enamel disorders. RESULTS:
      hypomineralization was observed in every single sample of the tetracyclic and
      amoxicillin treated group 100 mg/kg, meanwhile only 50% from the group
      administered with 50 mg/kg amoxicillin showed this histological disorder.
      CONCLUSIONS: the side effect caused by amoxicillin on dental enamel was doses
      dependent.

PMID- 24121905
TI  - Identification of the mandibular landmarks in a pediatric population.
AB  - OBJECTIVE: The aim of this study was to determine and compare the reliability to
      accomplish of common mandibular landmarks and to determine the incidence of
      incisive canals, anterior looping, and lingual foramina in children from
      panoramic and CBCT images. DESIGN: Panoramic and CBCT images from 100 children
      and adolescent patients were randomly selected. In order to grade the visibility
      of mandibular anatomical landmarks, a four-point rating scale was used. RESULTS:
      In panoramic images, the mandibular canal could be observed in 92.5% of cases,
      with good visibility in 12.0%. The mental foramen could be observed in 44.5% of
      cases, while none had good visibility. Anterior looping of the mental nerve was
      present in 16.5% of the cases, and none had good visibility. An incisive canal
      could be identified in 22.5% of cases, with only 1.5% showing good visibility.
      The lingual foramen could be visualized in 61.0% of cases, with good visibility
      in 6%. In CBCT images, the mandibular canal, the mental foramen, and the lingual
      foramen could be observed in 100% of the cases, with good visibility in 51.0%,
      98.5%, and 45.0% of cases, respectively. Anterior looping of the mental nerve was
      present in 26% of cases, with 2% having good visibility. An incisive canal could
      be identified in 49.5% of cases, with only 75% showing good visibility.
      CONCLUSIONS: This study confirms the applicability of CBCT images to visualize
      critical structures in children.

PMID- 24121906
TI  - Application of an oral health-related quality of life questionnaire in primary
      care patients with orofacial pain and temporomandibular disorders.
AB  - OBJECTIVES: To examine whether patients who report orofacial pain (OP) and
      temporomandibular disorders (TMD) have a poorer perception of their oral health
      related quality of life and, if so, to what extent, and to analyze the
      association between oral health perception, sociodemographic variables and
      reported pain duration. STUDY DESIGN: 407 patients treated at the OP and TMD
      units in the Healthcare District of Cordoba, Spain, diagnosed following the
      standard criteria accepted by the scientific community - the Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMD) - were administered the
      Spanish version of the Oral Health Impact Profile questionnaire (OHIP-14).
      Bivariate and logistic regression analyses were performed to determine the degree
      of association between the patients' OHIP-14 score and pain duration, pain
      intensity, and various sociodemographic variables. RESULTS: The observed
      distribution was 89.4% women and 10.6% men. The mean OHIP-14 score was 20.57 +/-
      10.73 (mean +/- standard deviation). A significant association (p<0.05) was found
      for gender, age, marital status, chronic pain grade, self-perceived oral health
      status and pain duration. CONCLUSIONS: The analysis of self-perceived oral health
      status in patients with OP and TMD, as measured by the OHIP-14, showed that oral
      health is perceived more negatively by women. Moreover, a one-point increase in
      the Chronic Pain Grade indicator increases the OHIP-14 indicator by 4.6 points,
      while chronic pain, defined as pain suffered by patients for one year or more,
      increases the OHIP-14 indicator by 3.2 points.

PMID- 24121907
TI  - A clinical-pathological and survival study of oral squamous cell carcinomas from
      a population of the North of Portugal.
AB  - OBJECTIVES: Our aim was to analyze the clinical, pathological, and outcome
      characteristics of oral squamous cell carcinomas (OSCC) from a population of the
      North of Portugal. MATERIAL AND METHODS: We conducted a descriptive study of 128
      OSCC diagnosed between the years of 2000 and 2010 in the Centro Hospitalar do
      Porto. Through of the review of the clinical records we studied several clinical,
      pathological, and outcome variables. The overall survival (OS) and disease-free
      survival (DFS) were analyzed by Kaplan-Meier method and log-rank test. Cox
      regression method was used for multivariate analysis. RESULTS: Of 128 patients
      with OSCC, 83 (64.8%) were male and 45 (35.2%) were female, (mean age of 62.13+/
      15.57 years). The most affected location was the tongue (n=52; 40.6%). The most
      common cause of reference was a non-healing ulcer (n=35; 28.9%) followed by oral
      pain (n=27; 22.3%). Sixty (60.6%) patients were tobacco consumers and 55 (57.3%)
      alcohol consumers. The cumulative 3-years OS rate was 58.6% and DFS was 55.4%. In
      multivariable analysis for OS, we found an adverse independent prognostic value
      for advanced tumour size (p<0.001) and for the presence of perineural permeation
      (p=0.012). For DFS, advanced stage tumours presented adverse independent
      prognostic value (p<0.001). CONCLUSION: OSCC occurred most frequently in males,
      in older patients, and in patients with tobacco and/or alcohol habits. TNM and
      tumour stage additionally to the perineural permeation were the most important
      prognostic factor for the survival of these patients, contributing to identify
      high-risk subgroups and to guide therapy.

PMID- 24121908
TI  - Evaluation of Dentaport ZX and Raypex 6 electronic apex locators: an in vivo
      study.
AB  - INTRODUCTION: Raypex 6 is an electronic apex locator (EAL) that has not yet been
      tested in vivo. The purpose of this in vivo study was to compare the accuracy of
      two EALs: the Dentaport ZX and the Raypex 6. METHODS: The study involved 36
      straight single-rooted teeth. A 10-K file was advanced until the EAL detected the
      major foramen. The file was fixed in a replaceable pattern of light-cured
      composite. The apical part of each canal was trimmed to expose the file tip. The
      distances from the file tips to the major foramen were measured. RESULTS:
      Wilcoxon's signed Rank test found no significant differences between the
      Dentaport ZX and Raypex 6 in terms of their abilities to detect the major foramen
      (P = .52) The Dentaport ZX was accurate 82.35% of the time to +/- 0.5 mm and
      97.05% of the time to +/- 1 mm, whereas the Raypex 6 was accurate 88.22% of the
      time to +/- 0.5 mm and 100% of the time to +/- 1 mm. CONCLUSIONS: No
      statistically significant differences were observed between the performance of
      the Dentaport ZX and Raypex 6 EALs under the in vivo clinical conditions used in
      this study.

PMID- 24121909
TI  - Assessment of Osstell ISQ's reliability for implant stability measurement: a
      cross-sectional clinical study.
AB  - Resonance frequency analysis (RFA) allows assess implant stability by measuring
      implant oscillation frequency on the bone. RFA is an objective and non-invasive
      method for implant stability measurement, although scarce evidence has been
      provided so far on its reliability. OBJECTIVE: Assess the Osstell ISQ system's
      reliability (i.e., its measurement reproducibility and repeatability) by means of
      the intraclass correlation coefficient (ICC) as statistical method. DESIGN OF THE
      STUDY: Two implant stability registers were completed by means of Osstell ISQ on
      85 implants on 23 patients. Six measurements were completed on each implant by
      means of two different SmartPegs (types I and II); that is, three consecutive
      measurements with each transducer. RESULTS: Average ISQ was 72.40, 72.22 and
      72.79, and 72.06, 72.59 and 72.82 in the first, second, and third measurements
      with SmartPegs I and II, respectively. Equal values or differences below three
      ISQ points were observed in 52.9% and 62.4% of the cases with SmartPegs I and II,
      respectively. The intraclass correlation coefficient was 0.97 for both SmartPegs,
      and repeatability and reproducibility also reached 0.97 for both SmartPegs.
      CONCLUSIONS: The RFA system Osstell ISQ presents almost perfect repeatability and
      reproducibility after intraclass correlation coefficient analysis. Osstell ISQ
      measurements are highly reliable regarding reproducibility. Therefore, one
      measurement proves enough.

PMID- 24121910
TI  - Genetic basis of dental agenesis--molecular genetics patterning clinical
      dentistry.
AB  - Tooth agenesis is one of the most common congenital malformations in humans.
      Hypodontia can either occur as an isolated condition (non-syndromic hypodontia)
      or can be associated with a syndrome (syndromic hypodontia), highlighting the
      heterogeneity of the condition. Though much progress has been made to identify
      the developmental basis of tooth formation, knowledge of the etiological basis of
      inherited tooth loss is still lacking. To date, the mutation spectra of non
      syndromic form of familial and sporadic tooth agenesis in humans have revealed
      defects in various such genes that encode transcription factors, MSX1 and PAX9 or
      genes that code for a protein involved in canonical Wnt signaling (AXIN2), and a
      transmembrane receptor of fibroblast growth factors (FGFR1). The aim of this
      paper is to review the current literature on the molecular mechanisms responsible
      for selective hypodontia in humans and to present a detailed overview of
      causative genes and syndromes associated with hypodontia. 

PMID- 24121911
TI  - Radiographic technical quality of root canal treatment performed ex vivo by
      dental students at Valencia University Medical and Dental School, Spain.
AB  - OBJECTIVES: To evaluate radiographically the quality of root canal fillings and
      compare manual and rotary preparation performed on extracted teeth by
      undergraduate dental students. STUDY DESIGN: A total of 561 premolars and molars
      extracted teeth were prepared using nickel-titanium rotary files or manual
      instrumentation and filled with gutta-percha using a cold lateral condensation
      technique, by 4th grade undergraduate students. Periapical radiographs were used
      to assess the technical quality of the root canal filling, evaluating three
      variables: length, density and taper. These data were recorded, scored and used
      to study the "technical success rate" and the "overall score". The length of each
      root canal filling was classified as acceptable, short and overfilled, based on
      their relationship with the radiographic apex. Density and taper of filling were
      evaluated based on the presence of voids and the uniform tapering of the filling,
      respectively. Statistical analysis was used to evaluate the quality of root canal
      treatment, considering p < 0.05 as a statistical significant level. RESULTS: The
      percentage of technical success was 44% and the overall score was 7.8 out of 10.
      Technical success and overall score were greater with rotary instruments (52%
      against 28% with a manual one, p < 0.001; 8.3 against 6.7 respectively, p <
      0.001). CONCLUSIONS: It appears that inexperienced operators perform better root
      canal treatment (RCT) with the use of rotary instrumentation.

PMID- 24121912
TI  - Management of dental extraction in patients with Haemophilia A and B: a report of
      58 extractions.
AB  - OBJECTIVES: Patients with inherited bleeding disorders are at high risk of
      bleeding following oral surgery and present challenges to the oral surgeons. Aim
      of this study was to report our experience in dental extraction in patients
      exhibiting Haemophilia A and B between 2007 and 2012. PATIENT AND METHODS: 58
      dental extractions in 15 patients during 19 interventions were performed.
      Replacement therapy with recombinant and plasma-derived factor VIII and IX was
      applied systematically in combination with antifibrinolytic treatment and local
      haemostatic measures. The following data were recorded: type of surgery, applied
      local haemostatic measures, general substitution, systemic antifibrinolytic
      agents and occurrence of postoperative bleeding complications. RESULTS: Two
      patients presented postoperative bleeding. One had secondary bleeding requiring
      additional injection of factor concentrates. The other one presented epistaxis
      which was managed conservatively with a nasal tamponade. CONCLUSIONS: Excellent
      haemostasis is achievable after dental extractions in patients with Haemophilia A
      and B by following a protocol using defined pre- and postoperative doses of
      factor concentrates in combination with haemostatic measures.

PMID- 24121913
TI  - Parental-caregiver perceptions of child oral health-related quality of life (P
      CPQ): Psychometric properties for the peruvian spanish language.
AB  - OBJECTIVES: The aim of the study was to cross-culturally adapt the Parental
      Caregiver Perceptions Questionnaire (P-CPQ) to the Peruvian Spanish language and
      assess its reliability and validity. STUDY DESIGN: To translate and cross
      cultural adapt the instrument, 60 parents answered the P-CPQ in two pilot tests.
      The final version of the P-CPQ was evaluated in 200 parents of children aged 11
      to 14 years, who were clinically examined for dental caries. The internal
      consistency was assessed by Cronbach's alpha coefficient while repeat
      administration of the P-CPQ on the same 200 children facilitated the test-retest
      reliability via intraclass correlation coefficient (ICC). Construct and
      discriminant validity were based on associations of the P-CPQ with global ratings
      of oral health and clinical groups, respectively. RESULTS: The mean (standard
      deviation) P-CPQ score was 15.64(11.89). Internal consistency was confirmed by a
      Cronbach's alpha of 0.84. Test-retest reliability revealed excellent
      reproducibility (ICC= 0.94). Construct validity was satisfactory, demonstrating
      significant correlations between global ratings (oral health and overall well
      being) and the total scale and for subscale. Discriminant validity was
      significant (p<0.001), supporting its ability to discriminate between clinical
      groups. CONCLUSIONS: The Peruvian Spanish P-CPQ has satisfactory psychometric
      properties to assess parental-caregivers perceptions on their children's oral
      health-related quality of life.

PMID- 24121914
TI  - Comparison between anterolateral thigh perforator free flaps and pectoralis major
      pedicled flap for reconstruction in oral cancer patients--a quality of life
      analysis.
AB  - The aim of this study was to compare the differences between anterolateral thigh
      perforator free flaps (ALTFF) and pectoralis major myocutaneous flap (PMMF) for
      reconstruction in oral cancer patients. Method Patients: who received free flap
      or PMMF reconstruction after ablation surgeries were eligible for the current
      study. The patients' demographic data, medical history, and quality of life
      scores(Medical Outcomes Study-Short Form-36 (MOS SF-36) and the University of
      Washington Quality of Life (UW-QOL) questionnaires were collected. RESULTS: 81 of
      118 questionnaires were returned (68.64%). There was significant differences
      between two groups in the gender (P<0.005). Patients reconstructed with ALTFF had
      better appearance domains and better shoulders domains, in addition to better
      role emotion domains. CONCLUSION: Using either PMMF or ALTFF for reconstruction
      of oral defects after cancer resection significantly influences a patient's
      quality of life. Data from this study provide useful information for physicians
      and patients during their discussion of reconstruction modalities for oral
      cancers.

PMID- 24121915
TI  - Effect of the local administration of betamethasone on pain, swelling and trismus
      after impacted lower third molar extraction. A randomized, triple blinded,
      controlled trial.
AB  - OBJECTIVES: The aim of this study is to compare the analgesic and anti
      inflammatory effects of the local postoperative administration of a single 12-mg
      dose of betamethasone after the surgical removal of impacted lower third molars.
      STUDY DESIGN: A split-mouth, triple-blind, randomized, placebo-controlled
      clinical trial of 25 patients requiring the surgical removal of symmetrical lower
      third molars was performed. In the experimental side, a 12-mg dose of
      betamethasone was administered submucosally after the surgical procedure, while
      in the control side a placebo (sterile saline solution) was injected in the same
      area. To assess postoperative pain, visual analogue scales and the consumption of
      rescue analgesic were used. The facial swelling and trismus were evaluated by
      measuring facial reference distances and maximum mouth opening. RESULTS: There
      were no significant differences between the two study groups regarding
      postoperative pain, facial swelling and trismus. CONCLUSIONS: The injection of a
      single dose of betamethasone does not seem to reduce pain, facial swelling and
      trismus after impacted lower third molar removal when compared to placebo.

PMID- 24121916
TI  - Burnout, depression and suicidal ideation in dental students.
AB  - OBJECTIVES: To investigate the prevalence, gender influence, and relationships
      between burnout, depression and suicidal ideation within the last year among
      second, fourth and fifth-year dental students. STUDY DESIGN: A cross-sectional
      study was carried out in 212 dental students enrolled in the second, fourth and
      fifth years at the School of Dentistry of Seville using the Maslach Burnout
      Inventory-Student Survey and the MBI-Human Services Survey, the "Patient Health
      Questionnaire-2", and the "Questions about Suicidal Ideation and Attempted
      Suicide". RESULTS: The response rate among dental students was 80%. Burnout
      prevalence in dental students was higher in second and fourth years than in fifth
      year (p = 0.059 and p = 0.003, respectively). Depression prevalence in the fourth
      year approached significance (p = 0.051). Prevalence of suicidal ideation within
      the past year was higher, yet not reaching significance, in fourth year. No
      gender-related differences were found. A significant association was observed
      between burnout and depression, and between depression and suicidal ideation (p <
      0.001), but no association was found between burnout and suicidal ideation.
      CONCLUSIONS: This study has brought our attention to the high prevalence of
      burnout and depression, and reported for the first time the prevalence of
      suicidal ideation among dental students in preclinical and clinical years.

PMID- 24121917
TI  - Soft tissue cell adhesion to titanium abutments after different cleaning
      procedures: preliminary results of a randomized clinical trial.
AB  - OBJECTIVES: A randomized controlled trial was performed to assess soft tissue
      cell adhesion to implant titanium abutments subjected to different cleaning
      procedures and test if plasma cleaning can enhance cell adhesion at an early
      healing time. STUDY DESIGN: Eighteen patients with osseointegrated and submerged
      implants were included. Before re-opening, 18 abutments were divided in 3 groups
      corresponding to different clinical conditions with different cleaning processes:
      no treatment (G1), laboratory customization and cleaning by steam (G2), cleaning
      by plasma of Argon (G3). Abutments were removed after 1 week and scanning
      electron microscopy was used to analyze cell adhesion to the abutment surface
      quantitatively (percentage of area occupied by cells) and qualitatively (aspect
      of adhered cells and presence of contaminants). RESULTS: Mean percentages of area
      occupied by cells were 17.6 +/- 22.7%, 16.5 +/- 12.9% and 46.3 +/- 27.9% for G1,
      G2 and G3 respectively. Differences were statistically significant between G1 and
      G3 (p=0.030), close to significance between G2 and G3 (p=0.056), and non
      significant between G1 and G2 (p=0.530). The proportion of samples presenting
      adhered cells was homogeneous among the 3 groups (p-valor = 1.000). In all cases
      cells presented a flattened aspect; in 2 cases cells were less efficiently
      adhered and in 1 case cells presented filipodia. Three cases showed contamination
      with cocobacteria. CONCLUSIONS: Within the limits of the present study, plasma of
      Argon may enhance cell adhesion to titanium abutments, even at the early stage of
      soft tissue healing. Further studies with greater samples are necessary to
      confirm these findings.

PMID- 24121919
TI  - Determination of periodontopathogens in patients with Cri du chat syndrome.
AB  - OBJECTIVES: Cri du chat syndrome is a genetic alteration associated with some
      oral pathologies. However, it has not been described previously any clinical
      relationship between the periodontal disease and the syndrome. The purpose of
      this comparative study was to compare periodontopathogenic flora in a group with
      Cri du chat syndrome and another without the sindrome, to assess a potential
      microbiological predisposition to suffer a periodontitis. STUDY DESIGN: The study
      compared nineteen subjects with Cri du chat Syndrome with a control group of
      nineteen patients without it. All patients were clinically evaluated by
      periodontal probing, valuing the pocket depth, the clinical attachmente level and
      bleeding on probing. There were no significant differences between both groups.
      Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
      intermedia, Tannerella forsythia and Treponema denticola were detected by
      multiplex-PCR using 16S rDNA (microIDENT). RESULTS: When A.
      actinomycetemcomitans, P. gingivalis, P. intermedia and T. denticola were
      compared, no statistically significant differences were found between the two
      groups (p>0.05). The value of T. forsythia was significantly higher for Cri du
      chat syndrome (31.6%) than for the control group (5.3%). The odds ratio for T.
      forsythia was 8.3. CONCLUSION: In the present study T. forsythia is associated
      with Cri du chat syndrome subjects and not with healthy subjects.

PMID- 24121918
TI  - Influence of the usual motivation for dental attendance on dental status and oral
      health-related quality of life.
AB  - OBJECTIVES: To evaluate the influence of dental visiting patterns on the dental
      status and Oral Health-related Quality of Life (OHQoL) of patients visiting the
      University Clinic of Salamanca (Spain). STUDY DESIGN: This cross-sectional study
      consisted of a clinical oral examination and a questionnaire-based interviewin a
      consecutive sample of patients seeking a dental examination. Patients were
      classified as problem-based dental attendees(PB) and regular dental
      attendees(RB). Clinical and OHQoL(OHIP-14 & OIDP)data were compared
      betweengroups. Pair-wise comparisons were performed and a Logistic Regression
      Model was fitted for predicting the Odds Ratio (OR) of being a PB patient.
      RESULTS: The sample was composed of 255 patients aged 18 to 87 years (mean age:
      63.1 +/- 12.7; women: 51.8%). The PB patients had a poorer dental status (i.e.
      caries, periodontal and prosthetic needs), brushed their teethless,and were
      significantly more impaired in their OHQoL according to both instruments.The
      logistic regression coefficients demonstrated that on average the OR of being a
      PB patient was high in this dental patient sample, but this OR increased
      significantly if the patient was a male (OR= 1.1-5.0) or referred pain-related
      impacts according to the OHIP and, additionally, the OR decreased significantly
      as a function of the number of healthy fillings and the number of sextants coded
      as CPI=0. CONCLUSIONS: Regular dental check-ups are associated with better dental
      status and a better OHQoL after controlling for potentially related confounding
      factors.

PMID- 24121920
TI  - Safety and efficacy of an intra-oral electrostimulator for the relief of dry
      mouth in patients with chronic graft versus host disease: Case series.
AB  - OBJECTIVES: Patients with chronic graft-versus-host disease (cGVHD) often suffer
      from dry mouth and oral mucosal lesions. The primary objective of this study was
      to investigate the safety of an intra-oral electrostimulator (GenNarino) in
      symptomatic cGVHD patients. The secondary objective was to study the impact on
      the salivary gland involvement of cGVHD patients. STUDY DESIGN: This paper
      presents a case series. The study included patients treated for 4 weeks, randomly
      assigned to the active device and then crossed-over to a sham-device or vice
      versa. The patients and clinicians were blind to the treatment delivered. Data
      regarding oral mucosal and salivary gland involvement were collected. RESULTS:
      Six patients were included in this series. Most of the intraoral areas with
      manifestations of cGVHD were not in contact with the GenNarino device. Two
      patients developed mild mucosal lesions in areas in contact with the GenNarino
      during the study. However, only one of them had a change in the National
      Institutes of Health (NIH) score for oral cGVHD. The unstimulated and stimulated
      salivary flow rate increased in 4 out of the 5 patients included in this
      analysis. Symptoms of dry mouth and general oral comfort improved. CONCLUSION:
      This study suggests that GenNarino is safe in cGVHD patients with respect to oral
      tissues. Furthermore the use of GenNarino resulted in subjective and objective
      improvements in dry mouth symptoms. A large scale study is needed to confirm the
      impact and safety of GenNarino on systemic cGVHD.

PMID- 24121921
TI  - Hospital dental practice in special patients.
AB  - Dental patients with special needs are people with different systemic diseases,
      multiple disorders or severe physical and/or mental disabilities. A Medline
      search was made, yielding a total of 29 articles that served as the basis for
      this study, which offers a brief description of the dental intervention protocols
      in medically compromised patients. Dental treatment in patients with special
      needs, whether presenting medical problems or disabilities, is sometimes complex.
      For this reason the hospital should be regarded as the ideal setting for the care
      of these individuals. Before starting any dental intervention, a correct patient
      evaluation is needed, based on a correct anamnesis, medical records and
      interconsultation reports, and with due assessment of the medical risks involved.
      The hospital setting offers the advantage of access to electronic medical records
      and to data referred to any complementary tests that may have been made, and we
      moreover have the possibility of performing treatments under general anesthesia.
      In this context, ambulatory major surgery is the best approach when considering
      general anesthesia in patients of this kind. 

PMID- 24121922
TI  - Dental treatment for handicapped patients; sedation vs general anesthesia and
      update of dental treatment in patients with different diseases.
AB  - Dental treatment on Handicapped Patients is often difficult because many people
      with a wide range of ages (from children to the elderly) with different
      pathologies that can affect the oral cavity and differ widely are included in
      this group. This situation creates some controversy, because according to
      pathology, each patient will be treated differently depending on collaboration,
      general health status, age or medication used to treat this pathologies.
      According to this situation we can opt for an outpatient treatment without any
      kind of previous medication, a treatment under conscious or deep sedation or a
      under general anesthesia treatment. With this systematic review is intended to
      help clarify in which cases patients should be treated under general anesthesia,
      sedation (conscious or deep) or outpatient clinic without any medication, as well
      as clarify what kind of treatments can be carried in private dental clinics and
      which should be carried out in a hospital. It will also discuss the most common
      diseases among this group of patients and the special care to be taken for their
      dental treatment. 

PMID- 24121923
TI  - Inherited, congenital and acquired disorders by hemostasis (vascular, platelet &
      plasmatic phases) with repercussions in the therapeutic oral sphere.
AB  - The hemostasis alterations, either congenital or hereditary origin, and acquired,
      are circumstances that hinder oral care to patients who suffer them and also
      generates in the professional who has to attend, high stress. Bleeding control
      once established and dental treatment planning, both in the aspect of
      preparation, as the realization of the odonto-stomatological therapeutic, has
      suffered updates that do need to remember certain aspects of the care of these
      patients. But we must not forget that the hematologist or internist who controls
      the patient's medical condition, is a cornerstone for the planning and
      implementation of treatment plans. We must also remember that, in certain
      circumstances, treatment should be performed in a hospital setting. In this
      review, we aim to provide the odonto-stomatologist guidance on how to address the
      problem and provide simple and updated guidelines to apply in the treatment of
      these people. 

PMID- 24121924
TI  - Clinical diseases with thrombotic risk and their pharmacologycal treatment: how
      they change the therapeutic attitude in dental treatments.
AB  - The new antiplatelets and anticoagulant drugs have been recently introduced in
      the daily medical practices for the control of thromboembolism associated with
      different diseases. The dental assistance of these patients forces us to know
      these drugs, understand their action mechanisms and try to decrease the risks
      that entail ours actions in these patients, making a thorough analysis of the
      risk of bleeding that is going to be related to our medical intervention, as well
      as the use of all the control measures of the hemorrhage from our knowledge with
      these patients, and to be prudent. The communication with the medical specialist
      that supervises these patients must be maxim, being necessary to make clinic
      trials for establishing protocols or guides of the handling with these patients
      during the odontological treatment. 

PMID- 24121925
TI  - The bacteremia of dental origin and its implications in the appearance of
      bacterial endocarditis.
AB  - Numerous systemic diseases may affect the oral cavity and vice versa,in
      particular severe diseases that involve the heart valve. In these cases,
      additional measures or a modification to our dental treatment need to be taken.
      We are aware of various diseases that can cause the emergence of bacterial
      endocarditis (BE), such as; rheumatic fever, valve lesions due to intravenous
      drug use, Kawasaki disease and valve surgery, among others. Due to its severity
      when it is not taken into account in dental treatment, we intend to show the
      evolution of the antimicrobial prophylaxis towards this condition. Furthermore,
      we intend to publish the current guidelines of institutions and societies which
      increasingly encourage rational antimicrobial use. In addition, we intend to
      examine the evidence of the possible origins of this disease during dental
      treatment and at the same time describe the necessary considerations that need to
      be taken during dental treatment. 

PMID- 24121926
TI  - Relationship between the oral cavity and cardiovascular diseases and metabolic
      syndrome.
AB  - The components of the human body are closely interdependent; as a result, disease
      conditions in some organs or components can influence the development of disease
      in other body locations. The effect of oral health upon health in general has
      been investigated for decades by many epidemiological studies. In this context,
      there appears to be a clear relationship between deficient oral hygiene and
      different systemic disorders such as cardiovascular disease and metabolic
      syndrome. The precise relationship between them is the subject of ongoing
      research, and a variety of theories have been proposed, though most of them
      postulate the mediation of an inflammatory response. This association between the
      oral cavity and disease in general requires further study, and health
      professionals should be made aware of the importance of adopting measures
      destined to promote correct oral health. The present study conducts a Medline
      search with the purpose of offering an update on the relationship between oral
      diseases and cardiovascular diseases, together with an evaluation of the
      bidirectional relationship between metabolic syndrome and periodontal disease.
      Most authors effectively describe a moderate association between the oral cavity
      and cardiovascular diseases, though they also report a lack of scientific
      evidence that oral alterations constitute an independent cause of cardiovascular
      diseases, or that their adequate treatment can contribute to prevent such
      diseases. In the case of metabolic syndrome, obesity and particularly diabetes
      mellitus may be associated to an increased susceptibility to periodontitis.
      However, it is not clear whether periodontal treatment is able to improve the
      systemic conditions of these patients. 

PMID- 24121927
TI  - A new cloning and expression system yields and validates TCRs from blood
      lymphocytes of patients with cancer within 10 days.
AB  - Antigen-specific T cell therapy, or T cell receptor (TCR) gene therapy, is a
      promising immunotherapy for infectious diseases and cancers. However, a suitable
      rapid and direct screening system for antigen-specific TCRs is not available.
      Here, we report an efficient cloning and functional evaluation system to
      determine the antigen specificity of TCR cDNAs derived from single antigen
      specific human T cells within 10 d. Using this system, we cloned and analyzed 380
      Epstein-Barr virus-specific TCRs from ten healthy donors with latent Epstein-Barr
      virus infection and assessed the activity of cytotoxic T lymphocytes (CTLs)
      carrying these TCRs against antigenic peptide-bearing target cells. We also used
      this system to clone tumor antigen-specific TCRs from peptide-vaccinated patients
      with cancer. We obtained 210 tumor-associated antigen-specific TCRs and
      demonstrated the cytotoxic activity of CTLs carrying these TCRs against peptide
      bearing cells. This system may provide a fast and powerful approach for TCR gene
      therapy for infectious diseases and cancers. 

PMID- 24121929
TI  - Dealing with scientific integrity issues: the Spanish experience.
AB  - Integrity has been an important matter of concern for the scientific community as
      it affects the basis of its activities. Most countries having a significant
      scientific activity have dealt with this problem by different means, including
      drafting specific legal or soft law regulations and the appointment of stable or
      ad hoc committees that take care of these questions. This has also been the case
      in Spain. After the period of transition between dictatorship to a democratic
      regime, and, particularly, after the entrance in the European Union, scientific
      activity has increased in the country. As it could be expected, problems of
      misconduct have appeared and different institutions have been dealing with these
      matters. One of the best examples is that of Consejo Superior de Investigaciones
      Cientificas (CSIC), the largest institution devoted to scientific research
      belonging to the Spanish Government. The experience of the CSIC's Ethics
      Committee in dealing with conflicts related to scientific practices is discussed
      here.

PMID- 24121930
TI  - Expressing antimicrobial peptide cathelicidin-BF in Bacillus  subtilis using SUMO
      technology.
AB  - Small ubiquitin-related modifier (SUMO) technology has been widely used in
      Escherichia coli expression systems to produce antimicrobial peptides. However,
      E. coli is a pathogenic bacterium that produces endotoxins and can secrete
      proteins into the periplasm, forming inclusion bodies. In our work, cathelicidin
      BF (CBF), an antimicrobial peptide purified from Bungarus fasciatus venom, was
      produced in a Bacillus subtilis expression system using SUMO technology. The
      chimeric genes his-SUMO-CBF and his-SUMO protease 1 were ligated into vector
      pHT43 and expressed in B. subtilis WB800N. Approximately 22 mg of recombinant
      fusion protein SUMO-CBF and 1 mg of SUMO protease 1 were purified per liter of
      culture supernatant. Purified SUMO protease 1 was highly active and cleaved his
      SUMO-CBF with an enzyme-to-substrate ratio of 1:40. Following cleavage,
      recombinant CBF was further purified by affinity and cation exchange
      chromatography. Peptide yields of ~3 mg/l endotoxin-free CBF were achieved, and
      the peptide demonstrated antimicrobial activity. This is the first report of the
      production of an endotoxin-free antimicrobial peptide, CBF, by recombinant DNA
      technology, as well as the first time purified SUMO protease 1 with high activity
      has been produced from B. subtilis. This work has expanded the application of
      SUMO fusion technology and may represent a safe and efficient way to generate
      peptides and proteins in B. subtilis.

PMID- 24121928
TI  - High-throughput identification of antigen-specific TCRs by TCR gene capture.
AB  - The transfer of T cell receptor (TCR) genes into patient T cells is a promising
      approach for the treatment of both viral infections and cancer. Although
      efficient methods exist to identify antibodies for the treatment of these
      diseases, comparable strategies to identify TCRs have been lacking. We have
      developed a high-throughput DNA-based strategy to identify TCR sequences by the
      capture and sequencing of genomic DNA fragments encoding the TCR genes. We
      establish the value of this approach by assembling a large library of cancer
      germline tumor antigen-reactive TCRs. Furthermore, by exploiting the quantitative
      nature of TCR gene capture, we show the feasibility of identifying antigen
      specific TCRs in oligoclonal T cell populations from either human material or TCR
      humanized mice. Finally, we demonstrate the ability to identify tumor-reactive
      TCRs within intratumoral T cell subsets without knowledge of antigen
      specificities, which may be the first step toward the development of autologous
      TCR gene therapy to target patient-specific neoantigens in human cancer. 

PMID- 24121931
TI  - Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic
      syndrome: an in vivo analysis using ZDF rats.
AB  - Metabolic syndrome, encompassing type 2 diabetes mellitus and cardiovascular
      disease, is a growing health concern of industrialized countries. Ferulic acid
      (FA) is a phenolic acid found in foods normally consumed by humans that has
      demonstrated antioxidant activity, cholesterol-lowering capabilities, and anti
      tumorigenic properties. Select probiotic bacteria, including Lactobacillus
      fermentum NCIMB 5221, produce FA due to intrinsic ferulic acid esterase activity.
      The aim of the present research was to investigate a FA-producing probiotic, L.
      fermentum NCIMB 5221, as a biotherapeutic for metabolic syndrome. The probiotic
      formulation was administered daily for 8 weeks to Zucker diabetic fatty (ZDF)
      rats, a model of hyperlipidemia and hyperglycemia. Results show that the
      probiotic formulation reduced fasting insulin levels and insulin resistance,
      significantly reduced serum triglycerides (p = 0.016), lowered serum low-density
      lipoprotein cholesterol levels (p = 0.008), and significantly reduced the
      atherogenic (p = 0.016) and atherosclerosis (p = 0.012) index as compared to the
      control animals. In addition, the probiotic formulation significantly increased
      high-density lipoprotein cholesterol levels (p = 0.041) as compared to the
      control animals. This research indicates that administration of the FA-producing
      L. fermentum NCIMB 5221 has the potential to reduce insulin resistance,
      hyperinsulinemia, hypercholesterolemia, and other markers involved in the
      pathogenesis of metabolic syndrome. Further studies are required to investigate
      the human clinical potential of the probiotic formulation in affecting the
      markers and pathogenesis of metabolic syndrome.

PMID- 24121933
TI  - Biotechnological applications and prospective market  of microbial keratinases.
AB  - Keratinases are well-recognized enzymes with the unique ability to attack highly
      cross-linked, recalcitrant structural proteins such as keratin. Their potential
      in environmental clean-up of huge amount of feather waste has been well
      established since long. Today, they have gained importance in various other
      biotechnological and pharmaceutical applications. However, commercial
      availability of keratinases is still limited. Hence, to attract entrepreneurs,
      investors and enzyme industries it is utmost important to explicitly present the
      market potential of keratinases through detailed account of its application
      sectors. Here, the application areas have been divided into three parts: the
      first one is dealing with the area of exclusive applications, the second
      emphasizes protease dominated sectors where keratinases would prove better
      substitutes, and the third deals with upcoming newer areas which still await
      practical documentation. An account of benefits of keratinase usage, existing
      market size, and available commercial sources and products has also been
      presented.

PMID- 24121934
TI  - Aqueous phase preparation of graphene with low defect density and adjustable
      layers.
AB  - Graphene sheets with an adjustable number of layers and a low defect density were
      prepared by exfoliation of microwave-assisted expanded graphite in the aqueous
      phase with the assistance of cetyltrimethylammonium bromide. The graphene sheets
      exhibit excellent film-formation ability, showing potential applications in
      optical and electrical device fields. 

PMID- 24121932
TI  - Bacterial chitinase with phytopathogen control capacity from suppressive soil
      revealed by functional metagenomics.
AB  - Plant disease caused by fungal pathogens results in vast crop damage globally.
      Microbial communities of soil that is suppressive to fungal crop disease provide
      a source for the identification of novel enzymes functioning as bioshields
      against plant pathogens. In this study, we targeted chitin-degrading enzymes of
      the uncultured bacterial community through a functional metagenomics approach,
      using a fosmid library of a suppressive soil metagenome. We identified a novel
      bacterial chitinase, Chi18H8, with antifungal activity against several important
      crop pathogens. Sequence analyses show that the chi18H8 gene encodes a 425-amino
      acid protein of 46 kDa with an N-terminal signal peptide, a catalytic domain with
      the conserved active site F175DGIDIDWE183, and a chitinase insertion domain.
      Chi18H8 was expressed (pGEX-6P-3 vector) in Escherichia coli and purified. Enzyme
      characterization shows that Chi18H8 has a prevalent chitobiosidase activity with
      a maximum activity at 35  degrees C at pH lower than 6, suggesting a role as
      exochitinase on native chitin. To our knowledge, Chi18H8 is the first chitinase
      isolated from a metagenome library obtained in pure form and which has the
      potential to be used as a candidate agent for controlling fungal crop diseases.
      Furthermore, Chi18H8 may also answer to the demand for novel chitin-degrading
      enzymes for a broad range of other industrial processes and medical purposes.

PMID- 24121935
TI  - In situ identification of crystal facet-mediated chemical reactions on
      tetrahexahedral gold nanocrystals using surface-enhanced Raman spectroscopy.
AB  - Direct monitoring of a metal-catalyzed reaction by surface-enhanced Raman
      scattering (SERS) is always a challenging issue as it needs bifunctional metal
      structures that have plasmonic properties and also act as catalysts. Here we
      demonstrate that the tetrahexahedral (THH) gold nanocrystals (Au NCs) with
      exposed {520} facets give highly enhanced Raman signals from molecules at the
      interface, permitting in situ observation of chemical transformation from para
      aminothiophenol (PATP) to 4,4'-dimercaptoazobenzene (DMAB). The origin of the
      intense SERS signals of DMAB is carefully investigated based on the comparison of
      the SERS spectra of PATP obtained with both the THH Au NCs and the Au nanospheres
      with the exposed {111} facets. It is elucidated that the high-index {520} facet
      rather than the localized surface plasmons of the THH Au NCs plays a key role in
      producing a high yield of the product DMAB which is accompanied by the selective
      enhancement of the characteristic Raman signals. 

PMID- 24121936
TI  - Membrane lipid profile alterations are associated with the metabolic adaptation
      of the Caco-2 cells to aglycemic nutritional condition.
AB  - Cancer cells can adapt their metabolic activity under nutritional hostile
      conditions in order to ensure both bioenergetics and biosynthetic requirements to
      survive. In this study, the effect of glucose deprivation on Caco-2 cells
      bioenergetics activity and putative relationship with membrane lipid changes were
      investigated. Glucose deprivation induces a metabolic remodeling characterized at
      mitochondrial level by an increase of oxygen consumption, arising from an
      improvement of complex II and complex IV activities and an inhibition of complex
      I activity. This effect is accompanied by changes in cellular membrane
      phospholipid profile. Caco-2 cells grown under glucose deprivation show higher
      phosphatidylethanolamine content and decreased phosphatidic acid content.
      Considering fatty acid profile of all cell phospholipids, glucose deprivation
      induces a decrease of monounsaturated fatty acid (MUFA) and n-3 polyunsaturated
      fatty acids (PUFA) simultaneously with an increase of n-6 PUFA, with consequent
      drop of n-3/n-6 ratio. Additionally, glucose deprivation affects significantly
      the fatty acid profile of all individual phospholipid classes, reflected by an
      increase of peroxidability index in zwitterionic phospholipids and a decrease in
      all anionic phospholipids, including mitochondrial cardiolipin. These data
      indicate that Caco-2 cells metabolic remodeling induced by glucose deprivation
      actively involves membrane lipid changes associated with a specific bioenergetics
      profile which ensure cell survival.

PMID- 24121937
TI  - Functional and fluorescence analyses of tryptophan residues in H+-pyrophosphatase
      of Clostridium tetani.
AB  - Homodimeric proton-translocating pyrophosphatase (H+-PPase; EC 3.6.1.1) maintains
      the cytoplasmic pH homeostasis of many bacteria and higher plants by coupling
      pyrophosphate (PPi) hydrolysis and proton translocation. H+-PPase accommodates
      several essential motifs involved in the catalytic mechanism, including the PPi
      binding motif and Acidic I and II motifs. In this study, 3 intrinsic tryptophan
      residues, Trp-75, Trp-365, and Trp-602, in H+-PPase from Clostridium tetani were
      used as internal probes to monitor the local conformational state of the
      periplasm domain, transmembrane region, and cytoplasmic domain, respectively.
      Upon binding of the substrate analog Mg-imidodiphosphate (Mg-IDP), local
      structural changes prevented the modification of tryptophan residues by N
      bromosuccinimide (NBS), especially at Trp-602. Following Mg-Pi binding, Trp-75
      and Trp-365, but not Trp-602, were slightly protected from structural
      modifications by NBS. These results reveal the conformation of H+-PPase is
      distinct in the presence of different ligands. Moreover, analyses of the Stern
      Volmer relationship and steady-state fluorescence anisotropy also indicate that
      the local structure around Trp-602 is more exposed to solvent and varied under
      different environments. In addition, Trp-602 was identified to be a crucial
      residue in the H+-PPase that may potentially be involved in stabilizing the
      structure of the catalytic region by site-directed mutagenesis analysis.

PMID- 24121938
TI  - Nine-year objective and subjective follow-up of the ultra-lateral anterior repair
      for cystocele.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the long-term
      objective and subjective outcomes of the native tissue ultra-lateral anterior
      repair for cystocele. METHODS: An observational study of patients from a single
      tertiary centre was carried out from January 1994 to December 2006. Patients who
      underwent an ultra-lateral anterior repair during this period were sent the
      Pelvic Floor Distress Inventory (PFDI) questionnaire and invited to return for a
      POP-Q examination. Symptoms of prolapse, stage of cystocele recurrence and
      reoperation rate were assessed at follow-up. RESULTS: Of the 135 patients
      recruited, 53 also had a POP-Q examination. Mean follow-up was 9.25 years (SD
      3.2). The anatomical recurrence rate was 45 % at 9.25 years, but only 26 % of
      patients had recurrent prolapse symptoms. Most recurrences (43 %) occurred at
      between 1 and 5 years. The reoperation rate for cystocele was 7.4 %. CONCLUSION:
      Despite these rates of anatomical and symptomatic recurrence, only 7.4 % of
      patients underwent repeat cystocele surgery. Thus, symptomatic/anatomical
      recurrence of prolapse often does not mandate surgical correction. Considering
      that mesh complications require surgical management in approximately 10-15 %,
      this study supports the notion that the use of mesh in anterior vaginal repairs
      to reduce the risk of "recurrence" needs careful discussion with each patient.

PMID- 24121939
TI  - Are the measurements of water-filled and air-charged catheters the same in
      urodynamics? Response to comments.

PMID- 24121941
TI  - [What policy? That of knowledge. In memoriam: Francesco De Fiore (2013)].

PMID- 24121940
TI  - Developmental competence and the induction of ectopic proboscises in Drosophila
      melanogaster.
AB  - Developmental competence is the response of a cell(s) to information.
      Determination of adult labial identity in Drosophila requires Proboscipedia (PB)
      and Sex combs reduced (SCR); however, co-ectopic expression of PB and SCR is not
      sufficient for induction of ectopic adult labial identity, because the
      developmental information supplied by PB and SCR is suppressed. The
      evolutionarily conserved LASCY, DYTQL, NANGE motifs, and the C-terminal domain of
      SCR are sequence elements that mediate some, or all, of the suppression of
      ectopic proboscis determination. Therefore, the developmentally competent
      primordial proboscis cells provide an environment devoid of suppression, allowing
      PB and SCR to determine proboscis identity. SCR derivatives lacking suppression
      sequences weakly induce ectopic proboscis transformations independently of PB,
      suggesting that SCR may be the activity required for induction of adult labial
      identity, as is the case for larval labial identity. A possible explanation for
      PB independence of SCR in determination of adult and embryonic labial identity is
      PB operates as a competence factor that switches SCR from determining T1 identity
      to labial identity during metamorphosis. Lastly, labial determination is not
      conserved between SCR and murine HOXA5, suggesting that SCR has acquired this
      activity during evolution.

PMID- 24121942
TI  - [Obesity: the epidemic of the new millennium between genetics and environment].
AB  - Obesity is a complex epidemic disease, resulting from the interaction of
      predisposing genetic factors and causal environmental and behavioral factors. The
      latter are primarily responsible for the recent epidemic. In recent years, genome
      wide association studies have identified genetic variants associated with the
      development of obesity. Though discoveries in this field may hopefully lead to a
      personalized approach to the prevention and management of obesity, so far
      lifestyle changes remain the only effective tool. It is extremely urgent to
      intervene because obesity-related diseases are increasingly encountered in young
      people and children. 

PMID- 24121943
TI  - [Dyslipidemia management with medical nutrition therapy: current status and
      perspectives].
AB  - In Italy, patients with dyslipidemia account for 15-20% of the adult population
      with major healthcare and socio-economic impact. According to the ESC/EAS
      guidelines for the management of dyslipidemias, desirable cholesterol and
      triglyceride levels can be achieved with a synergy between drug treatment and
      adequate diet therapy. However, what diets should be adopted? In this review
      article, different types of dietary treatments are compared, with a special focus
      on diet education. The new scientific frontier of nutrigenetics is also
      discussed. 

PMID- 24121944
TI  - [Sense of coherence and cardiovascular risk: an observational study].
AB  - The aim of this study was to analyze possible existing correlations among the
      three dimensions of the sense of coherence (SOC), as a psychosocial risk factor,
      and some other cardiovascular risk factors in a group of primary care patients.
      Seventy-one persons at high cardiovascular risk were identified by their general
      practitioners and invited to answer the 13 questions included in the Antonovsky's
      SOC questionnaire. Psychosocial risk evaluation, performed with SOC analysis, may
      provide an important added value in the identification of behavioral changes and
      cardiovascular risk reduction. 

PMID- 24121945
TI  - [A biophysical integrated approach to autoimmune nephrotic syndrome: case
      report].
AB  - Autoimmune nephrotic syndrome is often characterized by frequent recurrence. It
      is commonly associated with reduced response to steroid therapy and its clinical
      management may be challenging. We report a case in which the combination of
      standard therapy with a biophysical treatment resulted in both clinical
      improvement and disappearance of autoimmune markers. 

PMID- 24121946
TI  - [Oxidative stress management in elite athletes].
AB  - It is well known that strenuous exercise training can induce an overproduction of
      reactive oxygen species with subsequent impairment of cellular macromolecules and
      metabolism, leading to cellular dysfunction. In elite athletes, reactive oxygen
      species can add to other injurious factors for muscle tissue; therefore special
      precautions are required to avoid an increase in injury risk. 

PMID- 24121947
TI  - [Diagnosis, prognosis and treatment of "myocardial bridging": state of the art
      and unresolved issues].
AB  - The current gold standard for the diagnosis of myocardial bridging is
      conventional coronary angiography; however, it shows only indirect signs of the
      disease, due to the systolic compression of the artery caused by the myocardial
      bridge with narrowing of the lumen and diastolic relaxation. On the other hand,
      computed tomography coronary angiography, even though exposing to radiation,
      clearly demonstrates the intramural course, the overlying muscular bands and the
      surrounding tissues also in asymptomatic patients and in absence of systolic
      compression. The prognosis of patients with myocardial bridge is usually good,
      but further studies are needed to evaluate the long-term prognosis of these
      patients, the adequate diagnostic and preventive approach and to better discern
      which patients should be candidate to medical, percutaneous or surgical
      treatment. 

PMID- 24121948
TI  - [Role of multimodality imaging in patients undergoing transcatheter aortic valve
      implantation].
AB  - Aortic stenosis is a common disorder. Aortic valve replacement is indicated for
      symptomatic patients with severe aortic stenosis, as the prognosis of untreated
      patients is poor. However, despite aortic valve replacement can produce dramatic
      benefit in the setting of aortic stenosis, morbidity and mortality associated
      with surgery has fostered a search for alternatives. Transcatheter aortic valve
      replacement is a novel method to treat selected high-risk patients with aortic
      stenosis. Patient screening and anatomic measurements of the aortic root, aortic
      cusp heights, and the distance between aortic annulus and coronary ostia, as well
      as the evaluation of coronary arteries and peripheral arterial disease are of
      great importance to ensure procedural success . This review outlines the evolving
      role of non-invasive multimodality imaging, including echocardiography,
      multidetector computed tomography and cardiac magnetic resonance, in support of
      transcatheter aortic valve implantation, and describes how the multimodality
      imaging approach is crucial in this clinical setting. 

PMID- 24121949
TI  - [Diabetes mellitus, company agreements, guidelines, EBM, audit and daily
      practice].

PMID- 24121950
TI  - Effects of the dihydrolipoyl histidinate zinc complex against  carbon
      tetrachloride-induced hepatic fibrosis in rats.
AB  - PURPOSE: This study investigated the effects of an antioxidant, dihydrolipoyl
      histidinate zinc complex (DHLHZn), on the hepatic fibrosis in the carbon
      tetrachloride (CCl4) rat model. METHODS: The animals were divided into three
      groups: control, CCl4, and CCl4+DHLHZn. A histological assessment of the liver
      fibrosis was performed using stained liver samples. The oxidative stress and
      antioxidant levels were evaluated by measuring the malondialdehyde (MDA) and
      glutathione (GSH) levels in the liver. In addition, cultured human hepatic
      stellate cells (LI90) were exposed to antimycin-A (AMA) and divided into four
      groups: control, DHLHZn, AMA, and AMA+DHLHZn. The effects of DHLHZn on AMA
      induced fibrosis were evaluated by measuring the expression of transforming
      growth factor (TGF)-beta1 and collagen alpha1 (I). RESULTS: The hepatic fibrosis
      in the CCl4+DHLHZn group was attenuated compared to that in the CCl4 group. The
      MDA levels in the CCl4+DHLHZn group were significantly lower than those of the
      CCl4 group, whereas the GSH levels in the CCl4+DHLHZn group were significantly
      higher than those of the CCl4 group. Furthermore, the relative mRNA expression of
      TGF-beta1 and collagen alpha1 (I) in the AMA+DHLHZn group was significantly lower
      than that in the AMA group. CONCLUSION: DHLHZn may attenuate the hepatic fibrosis
      induced by CCl4 by decreasing the degree of oxidative stress.

PMID- 24121951
TI  - Efficacy of laparoscopic resection in elderly patients with colorectal cancer.
AB  - PURPOSE: The perioperative outcomes of laparoscopic colorectal surgery in elderly
      patients were compared with those of open surgery in elderly patients and those
      of laparoscopic surgery in nonelderly patients to evaluate the feasibility and
      efficacy of laparoscopic surgery in elderly patients with colorectal cancer.
      METHODS: The data of the patients who underwent surgical resection for colorectal
      cancer between January 2007 and September 2012 were retrospectively collected.
      The clinical backgrounds and outcomes of elderly patients (>= 70 years of age)
      who underwent laparoscopic surgery (EL group) were compared with those of elderly
      patients who underwent open surgery (EO group) and those of nonelderly patients
      (< 70 years of age) who underwent laparoscopic surgery (NL group). RESULTS:
      Compared with the EO group, the EL group showed significantly less blood loss (15
      versus 100 ml), fewer postoperative complications (10.7 versus 36.7 %), earlier
      resumption of an oral diet (4 versus 5 days) and shorter postoperative hospital
      stays (16 versus 28 days). A case-matched analysis showed similar results. All
      perioperative outcomes were equivalent between the EL and NL groups. CONCLUSIONS:
      Laparoscopic colorectal surgery in elderly patients with cancer was not only
      superior to open surgery in elderly patients, but also equivalent to laparoscopic
      surgery in nonelderly patients in terms of the postoperative outcomes.

PMID- 24121952
TI  - Nonpharmacological interventions for refractory chronic cough patients:
      systematic review.
AB  - BACKGROUND: For people with refractory chronic cough, nonpharmacological
      interventions are emerging as alternatives to antitussive medications. These
      treatments generally are delivered by physiotherapists and speech and language
      therapists and consist of education, breathing exercises, cough suppression
      techniques, and counselling. Although the number of studies investigating these
      treatment options has increased in recent years there has not been a systematic
      review of the efficacy of these treatment options. METHODS: Studies were searched
      for in EMBASE, AMED, Medline, CINAHL, and PsycINFO databases. Bibliographies of
      studies and reviews were searched by hand. Critical appraisal was carried out by
      one reviewer using the SIGN appraisal tools and Cochrane handbook for systematic
      reviews. RESULTS: From a total of 184 studies, 5 full-text English language
      articles were included in the review. Nonpharmacological interventions were found
      to significantly reduce cough reflex sensitivity, improve quality of life, and
      lead to reductions in cough severity and frequency. However, few studies used
      validated and reliable tools to measure cough severity and frequency thereby
      limiting the robustness of these findings. CONCLUSION: Present data support the
      use of two to four sessions of education, cough suppression techniques, breathing
      exercises, and counselling in order to achieve improvements in cough sensitivity
      and cough-related quality of life for people with chronic refractory cough. Due
      to the lack of validated outcome measures, results for other aspects of cough
      should be interpreted with caution. There is a need for additional larger-powered
      comparative studies investigating nonpharmacological interventions for refractory
      chronic cough.

PMID- 24121953
TI  - Flavonoid inhibitory pharmacodynamics on platelet function in physiological
      environments.
AB  - The complex relationship between flavonoid-based nutrition and cardiovascular
      disease may be dissected by understanding the activities of these compounds in
      biological systems. The aim of the present study was to explore a hierarchy for
      the importance of dietary flavonoids on cardiovascular health by examining the
      structural basis for inhibitory effects of common, dietary flavonoids (quercetin,
      apigenin, and naringenin) and the plasma metabolite, tamarixetin. Understanding
      flavonoid effects on platelets in vivo can be informed by investigations of the
      ability of these compounds to attenuate the function of these cells. Inhibition
      of platelet function in whole blood and plasma was structure-dependent. The order
      of potency was apigenin > tamarixetin > quercetin = naringenin indicating that in
      vivo, important functional groups are potentially a methylated B ring, and a non
      hydroxylated, planar C ring. Apigenin and the methylated metabolite of quercetin,
      tamarixetin significantly reduced thrombus volume at concentrations (5 MUM) that
      suggested their reported physiological levels (0.1-1 MUM) may exert low levels of
      inhibition. Flavonoid interactions with erythrocytes, leukocytes and human serum
      albumin in whole blood reduce their inhibitory activities against platelet
      function. The diminished inhibitory activity of flavonoids that we observed in
      whole blood and plasma indicated that these interactions do not overcome the
      attenuating effects of these compounds. Furthermore, inhibition of platelet
      aggregation by flavonoids was enhanced with increases in exposure time,
      indicating the potential for measurable inhibitory effects during resident plasma
      times. We conclude that flavonoid structures may be a major influence of their
      activities in vivo with methylated metabolites and those of flavones being more
      potent than those of flavonols and flavanones. 

PMID- 24121954
TI  - MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive
      nonfluent aphasia.
AB  - We report a 77-year-old man, presenting with progressive aphasia as an initial
      symptom, who developed severe dementia over the course of 20 months. Frontal
      cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology
      showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of
      MM2C. Cerebellum showed focal coarse, patchy staining in different sections of
      the molecular layer, diffuse fine punctuate and coarse PrP immunopositive
      deposits in the granule cell layer, and focal synaptic immunostaining in the
      molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation
      has not yet been described in an MM1+2C subtype by histotyping. 

PMID- 24121955
TI  - Smaller sized inhaled anesthetics have more potency on senescence-accelerated
      prone-8 mice compared with senescence-resistant-1 mice.
AB  - BACKGROUND: Increasingly more aged people with Alzheimer's disease (AD) must
      undergo surgery with general anesthesia for various reasons. Knowing the potency
      of common inhaled anesthetics on AD patients is important to minimize the
      quantity of inhaled anesthetics. Previous studies indicated that transgenic AD
      mice were more resistant to the common inhaled anesthetics than were wild-type
      mice. However, transgenic AD mice are associated with early-onset familial AD,
      which accounts for only 5% of the total AD patients in the clinic. Confirming the
      results using other animal AD models is still necessary. OBJECTIVE: The aim of
      this study was to evaluate the potency of common inhaled anesthetics in another
      AD animal model, the senescence-accelerated mouse prone-8 (SAMP-8) model.
      METHODS: The minimum alveolar concentration (MAC) was measured by tail clamping
      in the SAMP-8 and senescence-resistant-1 (SAMR-1) mice at 4, 6, 8, and 10 months
      of age (n = 13). A two-way ANOVA (age and strain as the two factors) was used to
      analyze the difference. RESULTS: The statistical results showed that both the age
      and strain factors had significant effects on the MAC values. The MAC of the SAMP
      8 mice was significantly lower than that of the SAMR-1 mice for the three inhaled
      anesthetics. The MAC values of the SAMP-8 mice decreased significantly with
      aging. CONCLUSIONS: The SAMP-8 mice were more sensitive to the three inhaled
      anesthetics than were the SAMR-1 mice.

PMID- 24121956
TI  - PLTP deficiency impairs learning and memory capabilities partially due to
      alteration of amyloid-beta metabolism in old mice.
AB  - Increased expression of phospholipid transfer protein (PLTP) was observed in the
      brains of Alzheimer's disease (AD) patients; however, the role of PLTP in the
      progress of AD is still poorly understood. The objective of this study was to
      evaluate the effect of PLTP deficiency on the recognition and metabolism of
      amyloid-beta (Abeta) in mice. We performed the Morris water maze to determine the
      learning and memory capabilities of 50-week age wild type mice (WT, n = 12) and
      PLTP knockout mice (PLTP-/-, n = 12). The levels of Abeta and amyloid-beta
      protein precursor (AbetaPP) were examined by ELISA and western blot,
      respectively. The levels and activity of beta- and gamma-secretases were
      determined by western blot and activity assay kit, respectively. Morris water
      maze results showed that PLTP deficiency significantly impaired recognition
      compared with WT mice. Levels of Abeta42 in the cortex and hippocampus was
      significantly increased, yet the levels of Abeta40 in the cortex was decreased in
      PLTP-/- compared with WT mice. No typical senile plaques were found in the WT or
      PLTP-/- mice. AbetaPP expression and beta-secretase activity were both
      significantly increased in PLTP-/- mice. Moreover, PLTP deficiency increased the
      expression of gamma-secretase catalytic units and decreased the content of
      apolipoprotein E. Therefore we concluded that PLTP deficiency impaired cognition
      and aggravated AD by enhancing the generation of Abeta in the cortex of old mice.

PMID- 24121957
TI  - Incomplete penetrance of the C9ORF72 hexanucleotide repeat expansions: frequency
      in a cohort of geriatric non-demented subjects.
AB  - We genotyped for the C9ORF72 hexanucleotide repeat expansion a population of 156
      non-demented elderly subjects, recruited in a geriatric unit as control group for
      association studies in patients with Alzheimer's disease (AD), and found two
      carriers (1.2%). The first was referred for subjective memory complaints, at age
      81. He was followed up until age 84 and did not develop dementia. The second was
      an 80-year old volunteer (spouse and caregiver of a patient with AD), non
      demented at time of recruitment. We have not had information on her condition
      since that time. These results suggest that the penetrance of the mutation is
      definitely incomplete. 

PMID- 24121958
TI  - Relationship among diffusion tensor imaging, EEG activity, and cognitive status
      in mild cognitive impairment and Alzheimer's disease patients.
AB  - Magnetic resonance (MR) diffusion tensor imaging (DTI) can detect microstructural
      alterations by means of fractional anisotropy (FA) in patients with dementia,
      also in relation to cognitive status. The present study aimed at investigating
      the possible relation among white matter damage in DTI, quantitative
      electroencephalography (EEG) spectral power, and cognitive status in Alzheimer's
      disease (AD) and mild cognitive impairment (MCI) patients. Forty-seven subjects
      (8 moderate AD, 18 mild AD, 12 MCI, and 9 healthy controls) underwent brain MR,
      neuropsychological evaluation, and resting EEG recording. A progressive increase
      of EEG delta and theta spectral power was observed from controls to patients,
      mainly in more anterior areas, with a parallel widespread decrease of beta power.
      Moreover, a progressive decrease of FA from controls to patients in frontal areas
      and in the corpus callosum (genu) was observed. Correlation analyses indicated
      convergence among EEG rhythms changes, DTI values, and cognitive status mainly
      over anterior areas. The decrease of FA values and EEG spectral power changes
      might represent markers of neurodegenerative dysfunction, possibly preceding
      macrostructural atrophy. 

PMID- 24121959
TI  - Quantitative evaluation of disease progression in a longitudinal mild cognitive
      impairment cohort.
AB  - Several neuropsychological tests and biomarkers of Alzheimer's disease (AD) have
      been validated and their evolution over time has been explored. In this study,
      multiple heterogeneous predictors of AD were combined using a supervised learning
      method called Disease State Index (DSI). The behavior of DSI values over time was
      examined to study disease progression quantitatively in a mild cognitive
      impairment (MCI) cohort. The DSI method was applied to longitudinal data from 140
      MCI cases that progressed to AD and 149 MCI cases that did not progress to AD
      during the follow-up. The data included neuropsychological tests, brain volumes
      from magnetic resonance imaging, cerebrospinal fluid samples, and apolipoprotein
      E from the Alzheimer's Disease Neuroimaging Initiative database. Linear
      regression of the longitudinal DSI values (including the DSI value at the point
      of MCI to AD conversion) was performed for each subject having at least three DSI
      values available (147 non-converters, 126 converters). Converters had five times
      higher slopes and almost three times higher intercepts than non-converters. Two
      subgroups were found in the group of non-converters: one group with stable DSI
      values over time and another group with clearly increasing DSI values suggesting
      possible progression to AD in the future. The regression parameters
      differentiated between the converters and the non-converters with classification
      accuracy of 76.9% for the slopes and 74.6% for the intercepts. In conclusion,
      this study demonstrated that quantifying longitudinal patient data using the DSI
      method provides valid information for follow-up of disease progression and
      support for decision making. 

PMID- 24121960
TI  - Three-dimensional quantitative imaging of telomeres in buccal cells identifies
      mild, moderate, and severe Alzheimer's disease patients.
AB  - Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's
      disease (AD) patients and cognitively normal age and gender-matched controls, we
      have for the first time examined changes in the 3D nuclear telomeric architecture
      of buccal cells among levels of AD severity based on five 3D parameters: i)
      telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear
      volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data
      indicate that matched controls have significantly different 3D telomere profiles
      compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct
      profiles were also evident for each AD severity group. An increase in telomere
      number and aggregation concomitant with a decrease in telomere length from normal
      to severe AD defines the individual stages of the disease (p < 0.0001). 

PMID- 24121961
TI  - A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early
      onset and unusually fast progressing dementia as well as lysosomal inclusions
      typically seen in Kufs disease.
AB  - Whole exome sequencing in a family with suspected dominant Kufs disease
      identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who,
      along with their father, developed progressive dementia and motor deficits in
      their early 30 s. All affected relatives had unusually rapid disease progression
      (on average 3.6 years from disease onset to death). In silico analysis of
      mutation p.Leu(381)Phe predicted more detrimental effects when compared to the
      common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of
      peripheral fibroblast cells of the proband showed lysosomal inclusions typical
      for Kufs disease. However, brain autopsy demonstrated typical changes of
      Alzheimer's disease. 

PMID- 24121962
TI  - Distribution of pathology in frontal variant Alzheimer's disease.
AB  - Atypical presentations of Alzheimer's disease (AD) have been described, including
      a "frontal" variant (fvAD), which presents with personality change and executive
      dysfunction similar to that seen in behavioral variant frontotemporal dementia
      (bvFTD). This clinical variation is thought to reflect the regional distribution
      of pathology, although few reports include autopsy confirmation. We compared
      three clinicopathological groups matched for age at diagnosis and disease
      duration; those with possible bvFTD who at autopsy had only AD (fvAD), those with
      typical AD clinically and pathologically, and those with typical clinical bvFTD
      confirmed pathologically. The density of neurons and AD-type pathology was
      quantified in the frontal association, occipital association, and entorhinal
      cortices and hippocampal CA1 regions. Immunohistochemistry for phosphorylated tau
      and amyloid-beta deposition was used to detect neurofibrillary tangles and
      plaques. Of the six core clinical features of the International Consensus
      Criteria, disinhibition, stereotyped behaviors, and executive dysfunction were
      most common, occurring in five of the six fvAD patients. Other features were
      rare. While there was no significant difference in neuron density between groups
      for any of the four regions, when the ratio of frontal:occipital pathology was
      examined, neuronal density in fvAD was significantly less than AD but similar to
      bvFTD. The frontal:occipital ratio of AD-type pathology was also greater in fvAD
      than AD. The findings of this study suggest a frontal variant of AD exists with
      features that mimic bvFTD and that this reflects a differential distribution of
      neurodegeneration with more marked pathology in the frontal cortex compared with
      the occipital cortex. 

PMID- 24121963
TI  - Corpus callosum shape and size changes in early Alzheimer's disease: a
      longitudinal MRI study using the OASIS brain database.
AB  - BACKGROUND: Alzheimer's disease (AD) has been shown to be associated with
      shrinkage of the corpus callosum mid-sagittal cross-sectional area (CCA).
      OBJECTIVE: To study temporal rates of corpus callosum atrophy not previously
      reported for early AD. METHODS: We used longitudinal MRI scans to study the rates
      of change of CCA and circularity (CIR), a measure of its shape, in normal
      controls (NC, n = 75), patients with very mild AD (AD-VM, n = 51), and mild AD
      (AD-M, n = 21). RESULTS: There were significant reduction rates in CCA and CIR in
      all three groups. While CCA reduction rates were not statistically different
      between groups, the CIR declined faster in AD-VM (p < 0.03) and AD-M (p < 0.0001)
      relative to NC, and in AD-M relative to AD-VM (p < 0.0004). CONCLUSION: CIR
      declines at an accelerated rate with AD severity. Its rate of change is more
      closely associated with AD progression than CCA or any of its sub-regions. CIR
      may be a useful group biomarker for objective assessment of treatments that aim
      to slow AD progression.

PMID- 24121964
TI  - Art therapy for Alzheimer's disease and other dementias.
AB  - Patients with dementias commonly experience neuropsychiatric symptoms that
      diminish their quality of life. Pharmacologic treatments for these symptoms are
      limited in their efficacy. In the absence of near-future prospects for a cure for
      degenerative dementias, treatments that improve neuropsychiatric symptoms and
      quality of life are needed. We explore the hypothesis that art therapy is useful
      in dementia by reviewing the extant literature. With appropriate structure,
      patients with dementia can produce and appreciate visual art. Case studies and
      several small trials suggest that art therapy engages attention, provides
      pleasure, and improves neuropsychiatric symptoms, social behavior, and self
      esteem. Whether these benefits generalize beyond the studio remains unknown. We
      offer a theoretical framework that motivates the use of art therapy and propose
      that clinical enquiry to establish methods, assess efficacy, and define optimal
      conditions for the use of art therapy in Alzheimer's and other dementing
      disorders is timely. 

PMID- 24121965
TI  - Pathogen-free husbandry conditions alleviate behavioral deficits and
      neurodegeneration in AD10 anti-NGF mice.
AB  - It has been suggested that systemic infection, occurring during aging and chronic
      neurodegenerative diseases, can evoke an immune response that aggravates the
      progression of neurodegeneration and cognitive decline. It has been shown that
      the AD11 neurodegeneration mouse model, expressing a recombinant anti-nerve
      growth factor (NGF) antibody, shows a milder phenotype when housed in murine
      pathogen-free (MPF) conditions with respect to AD11 mice reared in conventional
      (CV) housing. AD10 mice, a variant of the anti-NGF AD11 model, expressing only an
      immunoglobulin light chain for the transgenic anti-NGF antibody, in the absence
      of the corresponding transgenic antibody chain VH, exhibit a complex
      neurodegenerative phenotype, similar to that of AD11 mice. Here we show that the
      AD10 transgenic mice, housed in murine pathogen-free conditions (MPF-AD10 mice),
      also display a milder behavioral and neurodegenerative phenotype compared to the
      corresponding mice kept under conventional housing conditions (CV-AD10). As a
      first step toward the identification of mechanisms underlying this difference, a
      differential gene expression profiling was performed on brains from CV-AD10 and
      MPF-AD10 mice, showing a decrease of the immune response and neuroinflammation
      gene expression in MPF-AD10 mice. Results suggest that the activation of the
      immune response gene expression in the CV-AD10, in a microbially unprotected
      environment, might contribute to a more severe and progressive neurodegenerative
      phenotype, compared to the MPF mice. 

PMID- 24121966
TI  - Candidate blood proteome markers of Alzheimer's disease onset and progression: a
      systematic review and replication study.
AB  - A blood-based protein biomarker, or set of protein biomarkers, that could predict
      onset and progression of Alzheimer's disease (AD) would have great utility;
      potentially clinically, but also for clinical trials and especially in the
      selection of subjects for preventative trials. We reviewed a comprehensive list
      of 21 published discovery or panel-based (> 100 proteins) blood proteomics
      studies of AD, which had identified a total of 163 candidate biomarkers. Few
      putative blood-based protein biomarkers replicate in independent studies but we
      found that some proteins do appear in multiple studies; for example, four
      candidate biomarkers are found to associate with AD-related phenotypes in five
      independent research cohorts in these 21 studies: alpha-1-antitrypsin, alpha-2
      macroglobulin, apolipoprotein E, and complement C3. Using SomaLogic's SOMAscan
      proteomics technology, we were able to conduct a large-scale replication study
      for 94 of the 163 candidate biomarkers from these 21 published studies in plasma
      samples from 677 subjects from the AddNeuroMed (ANM) and the Alzheimer's Research
      UK/Maudsley BRC Dementia Case Registry at King's Health Partners (ARUK/DCR)
      research cohorts. Nine of the 94 previously reported candidates were found to
      associate with AD-related phenotypes (False Discovery Rate (FDR) q-value < 0.1).
      These proteins show sufficient replication to be considered for further
      investigation as a biomarker set. Overall, we show that there are some signs of a
      replicable signal in the range of proteins identified in previous studies and we
      are able to further replicate some of these. This suggests that AD pathology does
      affect the blood proteome with some consistency.

PMID- 24121967
TI  - Cerebral cortical microinfarcts at 7Tesla MRI in patients with early Alzheimer's
      disease.
AB  - Cerebral microinfarcts (CMIs) are a common finding in neuropathological studies
      of aging and dementia. Recently, it has become possible to detect CMIs in vivo.
      We studied CMI occurrence in 29 patients with mild cognitive impairment or early
      Alzheimer's disease (AD) and 22 non-demented individuals on 7Tesla MRI. CMI
      occurrence in patients (55%) and controls (45%) was not significantly different.
      In patients, CMI number tended to be related to microbleed number (p = 0.07).
      This first in vivo study of CMIs in early AD does not confirm findings from
      autopsy studies. Further studies are needed to clarify the role of CMIs in AD. 

PMID- 24121968
TI  - Neuropathology of parkinsonism in patients with pure Alzheimer's disease.
AB  - About one third of Alzheimer's disease (AD) patients develop some parkinsonian
      features, yet half of them do not have Lewy body pathology at autopsy. The
      neuropathological substrate of parkinsonism in AD is still unclear. In the
      present study, we measured neuronal and neurofibrillary tangles (NFTs) densities
      in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients,
      11 with and 11 without parkinsonism, here defined as the presence of bradykinesia
      and at least one of resting tremor, rigidity, or gait disorders. Our study showed
      that parkinsonism associated with AD was related to a significant loss of neurons
      both in the SN and in the putamen, suggesting pre-and postsynaptic alterations of
      the nigrostriatal pathway. Neuronal tau deposition was a less important factor as
      density of NFTs correlated with parkinsonism only in the SN but not in the
      putamen. We propose that a subgroup of pure AD patients develop parkinsonian
      symptoms as a result of neuronal loss in the basal ganglia, indicating a
      prominent subcortical involvement, which appears unrelated to the Braak stage of
      AD. 

PMID- 24121969
TI  - Animal spotting in Alzheimer's disease: an eye tracking study of object
      categorization.
AB  - We investigated rapid object categorization and, more specifically, the ability
      to detect a target object within a natural scene in people with mild Alzheimer's
      disease (AD) using a saccadic choice task. It has been suggested that the
      anatomical pathway likely used to initiate rapid oculomotor responses in the
      saccadic choice task could involve the Frontal Eye Field, a structure that is
      part of the dorsal attentional network, in which connectivity is disrupted in AD.
      Seventeen patients with mild AD and 23 healthy age-matched controls took part in
      the study. A group of 24 young healthy observers was included as it has been
      reported that normal aging affects eye movements. Participants were presented
      with pairs of colored photographs of natural scenes, one containing an animal
      (the target) and one containing various objects (distracter), displayed for 1 s
      left and right of fixation. They were asked to saccade to the scene containing an
      animal. Neither pathology nor age affected temporal (saccade latencies and
      durations) and spatial (saccade amplitude) parameters of eye movements. Patients
      with AD were significantly less accurate than age-matched controls, and older
      participants were less accurate than young observers. The results are interpreted
      in terms of noisier sensory information and increased uncertainty in relation to
      deficits in the magnocellular pathway. The results suggest that, even at a mild
      stage of the pathology, people exhibit difficulties in selecting relevant
      objects. 

PMID- 24121971
TI  - Impact of radiofrequency catheter ablation on echocardiographic  and
      cardiopulmonary performance in patients with ventricular  extrasystolic beats and
      suspected arrhythmia-induced  cardiomyopathy.
AB  - Integrated backscatter intravascular ultrasound (IB-IVUS) is a useful method for
      analyzing coronary plaque tissue. We evaluated whether tissue composition
      determined using IB-IVUS is associated with the progression of stenosis in
      coronary angiography. Sixty-three nontarget coronary lesions in 63 patients with
      stable angina were evaluated using conventional IVUS and IB-IVUS. IB-IVUS images
      were analyzed at 1-mm intervals for a length of 10 mm. After calculating the
      relative areas of the tissue components using the IB-IVUS system, fibrous volume
      (FV) and lipid volume (LV) were calculated through integration of the slices,
      after which percentages of per-plaque volume (%FV/PV, %LV/PV) and per-vessel
      volume (%FV/VV, %LV/VV) were calculated. Progression of coronary stenosis was
      interpreted from the increase in percent diameter stenosis (%DS) from baseline to
      the follow-up period (6-9 months) using quantitative coronary angiography. %DS
      was 24.1 +/- 12.8 % at baseline and 23.2 +/- 13.7 % at follow-up. Using IB-IVUS,
      LV was 31.7 +/- 10.5 mm3, and %LV/PV and %LV/VV were 45.6 +/- 10.3 % and 20.2 +/-
      6.0 %, respectively. FV, %FV/PV, and %FV/VV were 35.5 +/- 12.1 mm3, 52.1 +/- 9.5
      %, and 23.4 +/- 7.1 %, respectively. The change in %DS was -0.88 +/- 7.25 % and
      correlated closely with %LV/VV (r = 0.27, P = 0.03) on simple regression.
      Multivariate regression after adjustment for potentially confounding risk factors
      showed %LV/VV to be correlated independently with changes in %DS (r = 0.42, P =
      0.02). Logistic regression analysis after adjusting for confounding coronary risk
      factors showed LV (odds ratio 1.08; 95 % confidence interval 1.01-1.16; P = 0.03)
      and %LV/VV (odds ratio 1.13; 95 % confidence interval 1.01-1.28; P = 0.03) to be
      independent predictors of the progression of angiographic coronary stenosis. Our
      findings suggest that angiographic luminal narrowing of the coronary artery is
      likely associated with tissue characteristics. IB-IVUS may provide information
      about the natural progression of luminal narrowing in coronary stenosis.

PMID- 24121970
TI  - Experimental induction of type 2 diabetes in aging-accelerated mice triggered
      Alzheimer-like pathology and memory deficits.
AB  - Alzheimer's disease (AD) is an age-dependent neurodegenerative disease
      constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting
      for early-onset familial AD. Availability of a pertinent model representing
      sporadic AD is essential for testing candidate therapies. Emerging evidence
      indicates a causal link between diabetes and AD. People with diabetes are >1.5
      fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of
      accelerated aging displays many features occurring early in AD. Given the role
      played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non
      transgenic mouse model of accelerated aging, we examined if high fat diet-induced
      experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the
      brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8
      mice exhibited increased cerebral amyloid-beta, dysregulated tau-phosphorylating
      glycogen synthase kinase 3beta, reduced synaptophysin immunoreactivity, and
      displayed memory deficits, indicating Alzheimer-like changes. High fat diet
      induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD. 

PMID- 24121972
TI  - Assessment of ventricular relaxation and stiffness using early  diastolic mitral
      annular and inflow velocities in pediatric patients  with heart disease.
AB  - This study was undertaken to test the hypothesis that noninvasive
      echocardiographic indexes obtained using early diastolic mitral annular and
      inflow velocities reflect diastolic function in children. We included in this
      study 61 consecutive pediatric patients (age 0.4-13 years) who underwent cardiac
      catheterization for various heart diseases with biventricular circulation. Left
      ventricular (LV) pressure was measured using a high-fidelity manometer to obtain
      the time constant of relaxation (tau) and LV chamber stiffness (K).
      Echocardiography was simultaneously performed during catheterization. Data
      acquisition was repeated after the administration of dobutamine. The peak early
      mitral annular velocity (e') and tau showed a significant inverse correlation (r
      = -0.42). Receiver-operating characteristic (ROC) analysis to determine the 90th
      percentile of tau yielded an area under the curve (AUC) of 0.86 for a septal e' <
      6.2 cm/s, with sensitivity and specificity of 0.83. The dobutamine-induced
      changes in e' closely correlated with those in tau (r = -0.69). The deceleration
      time (DT) showed a significant but weak negative correlation with K (r = -0.35),
      and ROC analysis to determine the 90th percentile of Kappa yielded an AUC of 0.82
      for a DT <100 ms, with sensitivity of 0.80 and specificity of 0.77. The ratio of
      peak early mitral inflow velocity (E) to e' (E/e') significantly correlated with
      LV end-diastolic pressure (EDP; r = 0.48, P < 0.0005), and ROC analysis to
      determine the 90th percentile of EDP (>12.96 mmHg) yielded an AUC of 0.81 for an
      E/e' > 16.4, with sensitivity of 0.71 and specificity of 0.93. The e', DT, and
      E/e' values in our study reflect the diastolic function in our pediatric
      population. However, the weak correlations between these indexes and invasive
      measures of diastolic function suggest that these indexes are useful in detecting
      diastolic dysfunction but not in determining the absolute values of diastolic
      dysfunction. Therefore, a future study is warranted to develop an efficient
      algorithm for systematic noninvasive evaluation of LV diastolic function in
      children.

PMID- 24121973
TI  - Electroanatomically estimated length of slow pathway  in atrioventricular nodal
      reentrant tachycardia.
AB  - The length of the slow pathway (SP-L) in atrioventricular (AV) nodal reentrant
      tachycardia (NRT) has never been measured clinically. We studied the relationship
      among (a) SP-L, i.e., the distance between the most proximal His bundle (H)
      recording and the most posterior site of radiofrequency (RF) delivery associated
      with a junctional rhythm, (b) the length of Koch's triangle (Koch-L), (c) the
      conduction time over the slow pathway (SP-T), measured by the AH interval during
      AVNRT at baseline, and (d) the distance between H and the site of successful
      ablation (SucABL-L) in 26 women and 20 men (mean age 64.6 +/- 11.6 years), using
      a stepwise approach and an electroanatomic mapping system (EAMS). SP-L (15.0 +/-
      5.8 mm) was correlated with Koch-L (18.6 +/- 5.6 mm; R 2 = 0.1665, P < 0.005), SP
      T (415 +/- 100 ms; R 2 = 0.3425, P = 0.036), and SucABL-L (11.6 +/- 4.7 mm; R 2 =
      0.5243, P < 0.0001). The site of successful ablation was located within 10 mm of
      the posterior end of the SP in 38 patients (82.6 %). EAMS-guided RF ablation,
      using a stepwise approach, revealed individual variations in SP-L related to the
      size of Koch's triangle and AH interval during AVNRT. Since the site of
      successful ablation was also correlated with SP-L and was usually located near
      the posterior end of the SP, ablating anteriorly, away from the posterior end, is
      not a prerequisite for the success of ablation procedures.

PMID- 24121974
TI  - OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via
      CD36 mediated ROS production leading to NLRP3 inflammasome activation.
AB  - OBJECTIVE: IL-1beta is a master switch of inflammation and plays an important
      role in the pathogenesis of vascular disease. During early atherosclerosis
      development, it is not clearly understood how oxidized low density lipoprotein
      (oxLDL)induced signaling pathways control NLRP3 inflammasome activation and
      produce IL-1beta and promote foam cells formation. METHODS: The study used THP-1
      macrophage as cell model. Western blot quantified the oxLDL-induced NLRP3
      inflammasome related proteins. The FACS detected the expression of SR-A and CD36
      receptors on the cells, and caspase-1 activation in the cells. The DCFH-DA
      assayed the reactive oxygen species (ROS). Oil red O staining techniques examined
      the intracellular lipid droplet. RESULTS: The OxLDL remarkably increased not only
      IL-1beta mRNA transcription and pro-IL-1beta protein synthesis but also IL-1beta
      secretion in human macrophages. The activation of the NLRP3 inflammasome depended
      on oxLDL-induced generation of ROS, potassium efflux and cathepsin B activity.
      The OxLDL-induced ROS production that mediates IL-1beta maturation mainly
      depended on the scavenger receptor of CD36 but not SR-A. The secreted IL-1beta
      served as an autocrine function for promoting macrophage foam cells formation.
      CONCLUSIONS: These findings suggest that oxLDL-induced NLRP3 inflammasome
      activation mainly depends on CD36 involved in the progression of atherosclerosis
      by promoting oxLDL-mediated inflammation and foam cell formation.

PMID- 24121976
TI  - Multivariate analysis to predict letrozole efficacy in improving sperm count of
      non-obstructive azoospermic and cryptozoospermic patients: a pilot study.
AB  - We tested the hypothesis that letrozole increases sperm count in non-obstructive
      azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2
      oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations
      were randomized into two groups: 22 received letrozole 2.5 mg per day for 6
      months (Group 1: 6 azoospermic + 16 cryptozoospermic patients), while 24 received
      a placebo (Group 2: 5 azoospermic + 19 cryptozoospermic patients). The following
      data were collected: two semen analyses, clinical history, scrotal Duplex scans,
      body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin
      levels. Both before and after letrozole or placebo administration, the patients
      underwent two semen analyses and hormonal assessments. The differences were
      evaluated using the Mann-Whitney U test. The relationships between sperm
      concentration after letrozole administration with respect to FSH, T/E2 ratio,
      bilateral testicle volume and BMI before letrozole administration were assessed
      using multivariate analysis. The side effects were assessed using the chi-square
      test. Group 1 had sperm concentration (medians: 400-1.290 * 10(6) ml(-1); P<0.01)
      and motility (medians: class A from 2% to 15%; P<0.01), FSH, LH and T
      significantly increased, while Group 2 did not. E2 levels diminished
      significantly in Group 1, but not in Group 2. Eight patients in Group 1
      demonstrated side effects, whereas no patient side effects were observed in Group
      2. The sperm concentration after letrozole administration is inversely related to
      T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and
      testicular volume.

PMID- 24121975
TI  - The role of the immune system in idiopathic nephrotic syndrome: a review of
      clinical and experimental studies.
AB  - Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by
      proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and
      animal models have associated INS with changes in the immune response. The
      purpose of this article is to review clinical and experimental findings showing
      the involvement of the immune response in the pathogenesis of INS. The role of
      the immune system in INS has been shown by clinical and experimental studies.
      However, the pattern of immune response in patients with INS is still not clearly
      defined. Many studies show changes in the dynamics of T lymphocytes, especially
      the regulatory T cells. Alternatively, there are other reports regarding the
      involvement of the complement system and B lymphocytes in the pathophysiology of
      INS. Indeed, none of the immunological biomarkers evaluated were undeniably
      linked to changes in glomerular permeability and proteinuria. On the other hand,
      some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and
      MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of
      glomerulopathies. To understand the pathophysiology of INS, longitudinal studies
      are clearly needed. The characterization of the profile of the immune response
      might help the development of specific and individualized therapies, leading to
      clinical improvement and better prognosis.

PMID- 24121977
TI  - Asymptomatic Sertoli cell tumour diagnosed during azoospermia work-up.

PMID- 24121978
TI  - Chinese nomogram to predict probability of positive initial prostate biopsy: a
      study in Taiwan region.
AB  - Several nomograms for prostate cancer detection have recently been developed.
      Because the incidence of prostate cancer is lower in Chinese men, nomograms based
      on other populations cannot be directly applied to Chinese men. We, therefore,
      developed a model for predicting the probability of a positive initial prostate
      biopsy using clinical and laboratory data from a Chinese male population. Data
      were collected from 893 Chinese male referrals, 697 in the derivation set and 196
      in the external validation set, who underwent initial prostate biopsies as
      individual screening. We analyzed age, prostate volume, total prostate-specific
      antigen (PSA), PSA density (PSAD), digital rectal examinations (DRE) and
      transrectal ultrasound (TRUS) echogenicity. Logistic regression analysis
      estimated odds ratio, 95% confidence intervals and P values. Independent
      predictors of a positive biopsy result included advanced age, small prostate
      volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic
      or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an
      initial positive biopsy using these variables. The area under the receiver
      operating characteristic curve for the model was 88.8%, which was greater than
      that of the prediction based on total PSA alone (area under the receiver
      operating characteristic curve 74.7%). If externally validated, the predictive
      probability was 0.827 and the accuracy rate was 78.1%, respectively.
      Incorporating clinical and laboratory data into a prebiopsy nomogram improved the
      prediction of prostate cancer compared with predictions based solely on the
      individual factors.

PMID- 24121980
TI  - Rough contact is not always bad for interfacial energy coupling.
AB  - For the first time we report that by introducing sub-nm roughness on a Si
      surface, the energy coupling between a single layer graphene (SLG) and the Si
      substrate can be improved substantially. This is contrary to the traditional view
      that a rough surface contact will weaken the energy coupling, rather than improve
      it. Periodical grooves of 2 nm width and 2 nm spacing are introduced on the
      surface of a Si substrate. It is surprisingly found that when the groove depth
      (delta) is less than 0.54 nm, the interfacial thermal resistance decreases
      against the increasing delta (more than 10% decrease at delta = 0.54 nm). The
      observed finding is explained soundly with the interfacial C-Si bond tuning by
      the surface roughness. For delta < 0.54 nm, the C-Si bond length in the suspended
      graphene region is large, and graphene experiences a strong pulling-down force
      (attractive) from the Si substrate. On the other hand, the graphene in the
      supported region is in direct contact with Si and experiences an extremely strong
      repulsive force to balance the pulling-down force in the suspended region. The
      repulsive force on graphene in the supported region can reach a level of 228 MPa.
      This significantly increases the local energy coupling and offsets the energy
      coupling reduction in the suspended graphene region. The discovery in this work
      points out that for extremely soft materials like graphene, it is possible to
      tune the material-substrate bonding by introducing sub-nm roughness on the
      substrate surface to significantly improve interfacial energy coupling. 

PMID- 24121979
TI  - Can DNA fragmentation of neat or swim-up spermatozoa be used to predict pregnancy
      following ICSI of fertile oocyte donors?
AB  - This study compared the potential of assessing sperm DNA fragmentation (SDF) from
      neat semen and the subsequent swim-up (SU) procedure to predict pregnancy when
      conducting ICSI of fertile donor oocytes. Infertile females (n=81) were
      transferred embryos resulting from intracytoplasmic sperm injection (ICSI) of
      their partner's spermatozoa and proven donor oocytes. This model normalized the
      impact of female factor in putative sperm DNA repair. Semen was blindly assessed
      for SDF using Halosperm immediately following ejaculation (NS) and after swim-up
      at the time of ICSI fertilisation. There was a decrease in SDF values of the
      ejaculated semen sample following the swim-up protocol (P=0.000). Interestingly,
      pregnancy could be equally predicted from SDF values derived from either neat or
      swim-up semen samples. Receiver operator curves and the derived Youden's indices
      determined SDF cutoff values for NS and SU of 24.8% and 17.5%, respectively.
      Prediction of pregnancy from NS SDF had a sensitivity of 75% and a specificity of
      69%, whereas for SU SDF was 78% and 73%, respectively. While increased levels of
      SDF negatively impact reproductive outcome, we have shown that a reduction in SDF
      following sperm selection using ICSI with proven donor oocytes is not mandatory
      for achieving pregnancy. This suggests that a certain level of DNA damage that is
      not detectable using current technologies could be impacting on the relative
      success of assisted reproductive technology (ART) procedures. Consequently, we
      propose a modification of the so called 'iceberg model' as a possible rationale
      for understanding the role of SDF in reproductive outcome.

PMID- 24121981
TI  - Fibular shaft allograft support of posterior joint depression in tibial plateau
      fractures.
AB  - Posterior depression of the lateral articular surface of the tibial plateau can
      be difficult to elevate and support with morselized bone graft and internal
      fixation. Progressive collapse after open reduction and internal fixation has
      been described and can lead to failure in treatment. A standard anterolateral
      approach to the tibia may not allow direct reduction and stabilization of
      posterolateral joint depression given the anatomic barriers of the fibular
      collateral ligament and the proximal tibiofibular articulation. Posterolateral
      approaches to the tibial plateau have been described and may allow direct
      reduction of the articular depression. These approaches, however, require
      dissection close to the common peroneal nerve, and some approaches also require a
      proximal fibular osteotomy. The use of an intraosseous fibular shaft allograft as
      an adjunct to open reduction and internal fixation in select cases of depressed
      posterolateral tibial plateau fractures allows both reduction of the joint and
      stabilization of the articular segment through a single approach familiar to many
      orthopaedic surgeons.

PMID- 24121982
TI  - Distal Ulna Fractures: A Biomechanical Comparison of Locking Versus Nonlocking
      Plating Constructs.
AB  - OBJECTIVE: To determine the biomechanical properties of plating options for
      distal ulna fractures. METHODS: Fourth-generation ulna artificial bones were
      osteotomized and fixed with 4 different constructs: 2 locking compression plates
      (a straight 2.7-mm plate and a 2.4-mm T-plate) with both nonlocking and locking
      screws. The artificial bones underwent nondestructive tests to determine
      construct stiffness in flexion/extension and lateral bending. The final testing
      consisted of cyclical loading in axial torsion until implant failure. RESULTS:
      The straight plate fixation construct was significantly stiffer than the T-plate
      construct for both flexion/extension bending (P < 0.001) and radial/ulnar bending
      (P < 0.05). Nonlocking screws provided significantly stiffer fixation in flexion
      bending than locking screws (P < 0.05); however, no difference was found in
      extension bending. Conversely, locking screws were significantly stiffer in
      radial/ulnar bending than the nonlocking screws (P < 0.05). Failure under
      torsional cyclical loading was significantly different among constructs. The
      straight plate with nonlocking construct withstood the most half-cycles. The
      mechanisms of failure were unique to each type of fixation. CONCLUSIONS: These
      results do not show any clear biomechanical advantage of locked plating for
      fractures of the distal ulna. The increased stiffness associated with locked
      plating likely contributes to earlier and more pronounced failure mechanisms
      under repetitive axial torsion.

PMID- 24121983
TI  - Three-dimensional computed tomography-based modeling of sagittal cadaveric
      femoral bowing and implications for intramedullary nailing.
AB  - OBJECTIVES: To establish the nature and extent of femur sagittal bowing by
      determining outer and inner anterior cortex geometries and sizes using analytical
      3-dimensional computed tomography modeling and relate the resultant femoral
      curvature with the curvatures of available intramedullary nails. METHODS:
      Computed tomography scans were rendered in 3D using modeling software to
      reconstruct 2 geometries: (1) outer cortex and (2) medullary canal. Femoral bow
      in the sagittal plane and the anterior cortical thickness were measured. Three
      curvature points were selected on both the geometries. Exterior anterior cortex
      radius of curvature (AROC) and medullary canal radius of curvature (MROC) were
      compared within and between each femur pair. RESULTS: Three groups of femurs
      exhibiting significantly different geometry patterns emerged: (1) AROC
      significantly greater than MROC, (2) AROC equivalent to MROC, and (3) AROC
      significantly smaller than MROC. Anterior cortical thickness ranged from 2.2 to
      7.0 mm was significantly different for males versus females, and it varied
      inversely with age. CONCLUSIONS: The study confirms that the radius of curvature
      of most intramedullary nails exceeds the sagittal radius of curvature of most
      adult femurs (both AROC and MROC). An intramedullary nail selected based on the
      anterior curvature would impinge on the anterior cortices at the proximal and
      distal anterior aspects of the femur in specimens with AROC > MROC. Conversely,
      in specimens with AROC < MROC, an intramedullary nail selected based on the
      anterior curvature would impinge on the proximal and distal posterior cortices.
      That cortical thickness varied significantly in accordance with gender and age is
      also relevant to surgical planning. MROC, in addition to the AROC alone, should
      be one of several design parameters used to match specific intramedullary nail
      design to an individual patient.

PMID- 24121984
TI  - Return to duty after integrated orthotic and rehabilitation initiative.
AB  - OBJECTIVES: To determine the return to active duty rate of military service
      members undergoing lower extremity limb salvage while using a novel custom
      orthosis and specialized rehabilitation compared with those receiving a novel
      custom orthosis alone. DESIGN: Retrospective cohort study. SETTING: Military
      level I trauma center and tertiary referral center for limb salvage.
      PATIENTS/PARTICIPANTS: All active duty service members enrolled in our
      institution's Return to Run Clinical Pathway were analyzed retrospectively.
      Service members were enrolled if they sustained injuries with residual disability
      below the knee. Injuries typically involved substantial motor and/or nerve
      deficit, and the overwhelming majority was secondary to high-energy injuries.
      INTERVENTION: Service members were fitted with a customized orthosis, an Intrepid
      Dynamic Exoskeletal Orthosis (IDEO), for use during rehabilitation. Service
      members were divided into 2 groups: those who had participated in the Return to
      Run Clinical Pathway with an IDEO (group 1) and those who only were fitted with
      an IDEO only (group 2). MAIN OUTCOME MEASURE: Return to military active duty
      rate. RESULTS: One hundred forty-six service members met the inclusion criteria.
      Group 1 consisted of 115 service members and group 2 consisted of 31 service
      members. Of those in group 1, 59 (51.3%) returned to active duty compared with 4
      (12.9%) in group 2 (P = 0.0001). Mechanisms of injury were significant factors
      for return to duty (RTD), and those sustaining explosive mechanisms of injury or
      gunshot wounds had significantly lower RTD rates across both groups. CONCLUSIONS:
      Active duty service members participating in an integrated orthotic and
      rehabilitation initiative after a lower extremity injury have a higher rate of
      RTD than previous reports, and it is significantly higher than the orthotic
      device alone.

PMID- 24121985
TI  - Mismatch of the short straight cephalomedullary nail (PFNA-II) with the anterior
      bow of the Femur in an Asian population.
AB  - OBJECTIVES: The aims of this study were to evaluate the morphologic discrepancies
      between the short straight proximal femoral nail antirotation-Asian version (PFNA
      II) and the anterior bow of the femur in Chinese patients and to propose a
      further design modification. DESIGN: Retrospective study. SETTING: Level I
      academic trauma center. PATIENTS/PARTICIPANTS: A consecutive 158 cases (35 men
      and 123 women with mean age of 77.2 years) with unstable per/intertrochanteric
      fractures (AO/OTA 31 A2 and A3) treated by PFNA-II from August 2008 to December
      2010 participated in this study. INTERVENTION: Nailing of PFNA-II. MAIN OUTCOME
      MEASUREMENTS: The nail tip position was classified to a 5-grade scale on
      postoperative lateral radiographs of the femur. The distance between the nail
      axis and the canal axis at the tip level was measured. The degree of the
      theoretical bent curvature and its corresponding radius were calculated, assuming
      that the anterior protrusive nail tip was placed back to the central canal axis.
      RESULTS: The distal tip of PFNA-II was located anterior to the femur canal
      central axis in 118 cases (74.7%), of which 55 cases abutted against the anterior
      cortex (contact between nail and internal cortex) (34.8%). With longer nails, the
      abutment occurred more often and was more prominent. For nail lengths of 170,
      200, and 240 mm, the theoretical distance to replace the nail tip to the central
      canal axis was 1.42 +/- 0.18, 1.77 +/- 0.39, and 2.46 +/- 0.20 mm, respectively;
      the corresponding bent curvature angle was 2.51 +/- 2.40, 2.13 +/- 1.65, and 2.09
      +/- 0.98 degrees, respectively; and the bent curvature radius was 1483 +/- 818,
      2329 +/- 1293, and 3710 +/- 1957 mm, respectively. CONCLUSIONS: There is a
      mismatch between the current short straight PFNA-II and the anterior bow of the
      femur in the Chinese population. In light of the documented complications and
      technical problems related to this mismatch, further modifications with an
      anterior bow are proposed.

PMID- 24121986
TI  - Bisphosphonate-associated fractures of the femur: pathophysiology and treatment.

PMID- 24121987
TI  - Invited commentary.

PMID- 24121988
TI  - Acremonium strictum: Report of a Rare Emerging Agent of Cutaneous
      Hyalohyphomycosis with Review of Literatures.
AB  - We present a case of cutaneous hyalohyphomycosis due to Acremonium strictum in an
      immunocompetent individual along with an overview of fungal infections caused by
      A. strictum. The diagnosis was confirmed by the presence of hyphae in microscopic
      examination of cutaneous biopsy and discharge, positive culture for A. strictum
      and sequencing of the isolate at reference centre. The infection resolved with
      itraconazole and terbinafine. Cutaneous or subcutaneous infections of A. strictum
      have rarely been reported. Fungemia or disseminated infection often with fatal
      outcome in immunocompromised patients was the most common presentation of A.
      strictum infection found in the literatures. The studies also reveal worldwide
      variation in the treatment regime and outcome of the treatment.

PMID- 24121989
TI  - Psychiatric features in gelastic epilepsy and hypothalamic hamartoma: long-term
      psychodiagnostic observations.

PMID- 24121991
TI  - In vitro and ex vivo retina angiogenesis assays.
AB  - Pathological angiogenesis of the retina is a key component of irreversible causes
      of blindness, as observed in proliferative diabetic retinopathy, age-related
      macular degeneration, and retinopathy of prematurity. Seminal studies in the
      early 1980 s about the angiogenic activity exerted by mammalian retinal tissue
      extracts on the chick embryo chorioallantoic membrane and the later discovery of
      vascular endothelial growth factor (VEGF) accumulation in eyes of patients with
      diabetic retinopathy paved the way for the development of anti-angiogenic VEGF
      blockers for the treatment of retinal neovascularization. Since then, numerous
      preclinical and clinical studies about diabetic retinopathy and other retinal
      disorders have opened new lines of angiogenesis inquiry, indicating that
      limitations to anti-VEGF therapies may exist. Moreover, the production of growth
      factors other than VEGF may affect the response to anti-VEGF approaches. Thus,
      experimental models of retinal angiogenesis remain crucial for investigating
      novel anti-angiogenic therapies and bringing them to patients. To this aim, in
      vitro and ex vivo angiogenesis assays may be suitable for a rapid screening of
      potential anti-angiogenic molecules before in vivo validation of the putative
      lead compounds. This review focuses on the different in vitro and ex vivo
      angiogenesis assays that have been developed over the years based on the
      isolation of endothelial cells from the retina of various animal species and ex
      vivo cultures of neonatal and adult retina explants. Also, recent observations
      have shown that eye neovascularization in zebrafish (Danio rerio) embryos, an in
      vivo animal platform experimentally analogous to in vitro/ex vivo models, may
      represent a novel target for the identification of angiogenesis inhibitors. When
      compared to in vivo assays, in vitro and ex vivo models of retina
      neovascularization, including zebrafish embryo, may represent cost-effective and
      rapid tools for the screening of novel anti-angiogenic therapeutics.

PMID- 24121990
TI  - In situ cell manipulation through enzymatic hydrogel photopatterning.
AB  - The physicochemical properties of hydrogels can be manipulated in both space and
      time through the controlled application of a light beam. However, methods for
      hydrogel photopatterning either fail to maintain the bioactivity of fragile
      proteins and are thus limited to short peptides, or have been used in hydrogels
      that often do not support three-dimensional (3D) cell growth. Here, we show that
      the 3D invasion of primary human mesenchymal stem cells can be spatiotemporally
      controlled by micropatterning the hydrogel with desired extracellular matrix
      (ECM) proteins and growth factors. A peptide substrate of activated
      transglutaminase factor XIII (FXIIIa)--a key ECM crosslinking enzyme--is rendered
      photosensitive by masking its active site with a photolabile cage group. Covalent
      incorporation of the caged FXIIIa substrate into poly(ethylene glycol) hydrogels
      and subsequent laser-scanning lithography affords highly localized biomolecule
      tethering. This approach for the 3D manipulation of cells within gels should open
      up avenues for the study and manipulation of cell signalling.

PMID- 24121992
TI  - Spectroscopy of single nanocrystals.
AB  - As colloidal semiconductor nanocrystals are developed for a wider range of
      diverse applications, it becomes more important to gain a deeper understanding of
      their properties in order to direct synthetic efforts. While most synthetic
      developments are guided by changes in ensemble properties, certain applications
      such as those in nano-electronics and nano-photonics rely on properties of
      nanocrystals at the individual level. For such applications and even for a more
      detailed understanding of the ensemble behavior, single nanocrystal spectroscopy
      becomes a vital tool. This review looks at how single nanocrystal spectroscopy
      has been applied to materials based on modern synthetic techniques and how these
      studies are elucidating properties that remain hidden at the ensemble level.
      First, recent theoretical models that are important for understanding many
      observed phenomena are explored. Then the review highlights new insights into
      many of the photophysical properties that are of interest in semiconductor
      nanocrystal materials, such as the ubiquitous spectral instability, magneto
      optical identification of the band-edge exciton fine structure, emission from
      multi-excitons, and the spectroscopic properties of charged nanocrystals that
      challenge long standing theories on photoluminescence blinking behavior. To date
      most of the research has been conducted on materials based on cadmium selenide
      primarily due to its many years of development as a prototypical nanocrystal
      system. The review ends with a discussion of new materials that would also
      benefit from a detailed photophysical understanding afforded by single
      nanocrystal spectroscopy. 

PMID- 24121993
TI  - Bio-distribution study of Reolysin(r) (pelareorep) through a single intravenous
      infusion in Sprague-Dawley rats.
AB  - Numerous pre-clinical and clinical studies on reovirus have generated valuable
      information which supports the use of this orphan virus as an investigational
      drug for cancer treatment. Reolysin(r) (pelareorep) is a clinical formulation of
      the human Reovirus Type 3 Dearing strain. The clinical safety and efficacy of
      Reolysin(r) in humans is being tested on an assortment of cancer indications as a
      mono and/or combination therapy. Reovirus has many inherent characteristics that
      make it a potential candidate for virotherapy, including: the rapid and natural
      spread through the haematogenous route, the ability to overcome immunological
      barriers thereby reaching tumor sites, and being replication-competent. The
      purpose of this study was to elucidate the bio-distribution pattern of
      Reolysin(r) in healthy Sprague-Dawley rats. Following a single 15-min intravenous
      infusion via the tail vein in Sprague-Dawley rats, the levels of virus genome
      were determined in 16 organs/tissues by RT-qPCR (Reverse Transcriptase-
      Quantitative Polymerase Chain Reaction) over a 336 h (Day 15) incubation regime.
      Consistent with previous studies, maximal reovirus RNA levels were observed in
      the spleen; indicating its involvement in viral uptake and clearance, followed by
      heart, ovaries, tail (infusion site), liver and lungs. All the organs/tissues
      demonstrated unquantifiable levels of reovirus genome at the end of incubation,
      suggesting substantial to complete viral clearance. Several studies in the last
      decade have described the use of reovirus for treating ovarian cancers. An
      increase of reovirus genome in ovaries at 24 h post infection was noted. The
      results will aid in the design of additional exploratory clinical trials for
      Reolysin(r).

PMID- 24121994
TI  - Early immunotherapy using autologous adult stem cells reversed the effect of anti
      pancreatic islets in recently diagnosed type 1 diabetes mellitus: preliminary
      results.
AB  - BACKGROUND: Bone marrow stem cell treatment has been proven a promising
      therapeutic strategy and showed significant results given the strong immune
      modulating properties. We have investigated the safety and efficacy of autologous
      bone marrow stem cell transplantation through liver puncture in two patients with
      recently diagnosed type 1 diabetes mellitus. MATERIAL AND METHODS: The procedure
      was approved by the Institutional Ethics Committee. In 2011, in three young
      patients, type 1 diabetes mellitus diagnosis was confirmed, with the presence of
      positive antibodies and ketoacidosis. Two patients was treated with autologous
      bone marrow stem cell stimulated with filgrastim and transplantation, through
      liver puncture, as immune modulators. One patients was treated with conventional
      treatment and participate in this experiment as a control group. The families of
      the patients signed the informed consent. No specific statistical analysis was
      performed. The patients had less than 8 years old, diagnosis of type 1 diabetes
      for less than 60 days, body mass index less than 22 kg/m2, normal complete blood
      count, coagulation and renal function, no lesions in target organs, glycosylated
      hemoglobin (HbA1c) level less than 13.70%, c-peptide level less than 0.67 ng/ml,
      positive results of Islets Cells Antibody (ICA), Glutamic Acid Decarboxylase
      (GAD) and insulin antibody. RESULTS: In two patients treated, the follow up at 12
      months showed negative value in ICA, GAD and anti insulin antibody levels, with
      an increased levels of c peptide and decreased levels of blood glucose and HbA1c.
      CONCLUSIONS: Treatment with autologous bone marrow stem cells is easy and
      effective as it reversed the production and effect of anti pancreatic islet
      antibody and significantly resulted in an increased c-peptide concentration.

PMID- 24121996
TI  - A metal ion triggered shrinkable supramolecular hydrogel and controlled release
      by an amphiphilic peptide dendron.
AB  - Divalent metal ions were found to trigger the shrinkage of a supramolecular
      hydrogel based on a peptide dendron, and the shrinkable gel could be further used
      to control the release of vitamin B1. 

PMID- 24121995
TI  - Dietary fat, fatty acid saturation and mitochondrial bioenergetics.
AB  - Fat intake alters mitochondrial lipid composition which can affect function. We
      used novel methodology to assess bioenergetics, including simultaneous ATP and
      reactive oxygen species (ROS) production, in liver and heart mitochondria of
      C57BL/6 mice fed diets of variant fatty acid content and saturation. Our
      methodology allowed us to clamp ADP concentration and membrane potential
      (DeltaPsi) at fixed levels. Mice received a control diet for 17-19 weeks, a high
      fat (HF) diet (60% lard) for 17-19 weeks, or HF for 12 weeks followed by 6-7
      weeks of HF with 50% of fat as menhaden oil (MO) which is rich in n-3 fatty
      acids. ATP production was determined as conversion of 2-deoxyglucose to 2
      deoxyglucose phosphate by NMR spectroscopy. Respiration and ATP production were
      significantly reduced at all levels of ADP and resultant clamped DeltaPsi in
      liver mitochondria from mice fed HF compared to controls. At given DeltaPsi, ROS
      production per mg mitochondrial protein, per unit respiration, or per ATP
      generated were greater for liver mitochondria of HF-fed mice compared to control
      or MO-fed mice. Moreover, these ROS metrics began to increase at a lower DeltaPsi
      threshold. Similar, but less marked, changes were observed in heart mitochondria
      of HF-fed mice compared to controls. No changes in mitochondrial bioenergetics
      were observed in studies of separate mice fed HF versus control for only 12
      weeks. In summary, HF feeding of sufficient duration impairs mitochondrial
      bioenergetics and is associated with a greater ROS "cost" of ATP production
      compared to controls. These effects are, in part, mitigated by MO.

PMID- 24121997
TI  - An innovative sample-to-answer polymer lab-on-a-chip with on-chip reservoirs for
      the POCT of thyroid stimulating hormone (TSH).
AB  - A new sample-to-answer polymer lab-on-a-chip, which can perform immunoassay with
      minimum user intervention through on-chip reservoirs for reagents and single
      channel assay system, has been designed, developed and successfully characterized
      as a point-of-care testing (POCT) cartridge for the detection of thyroid
      stimulating hormone (TSH). Test results were obtained within 30 minutes after a
      sample was dropped into the POCT cartridge. The analyzed results of TSH showed a
      linear range of up to 55 MUIU mL(-1) with the limit of detection (LOD) of 1.9
      MUIU mL(-1) at the signal-to-noise ratio (SNR) of 3. The reagents stored in the
      on-chip reservoirs maintained more than 97% of their initial volume for 120 days
      of storage time while the detection antibody retained its activity above 98% for
      120 days. The sample-to-answer polymer lab-on-a-chip developed in this work using
      the mass-producible and low-cost polymer is well suited for the point-of-care
      testing of rapid in vitro diagnostics (IVD) of TSH. 

PMID- 24121998
TI  - An investigation of the association between omega 3 FA and bone mineral density
      among older adults: results from the National Health and Nutrition Examination
      Survey years 2005-2008.
AB  - SUMMARY: The relation of omega 3 fatty acids (n-3 FA) with bone mineral density
      (BMD) was assessed among adults >60 years; NHANES data (2005-2008). The
      association of dietary n-3 FA with measures of hip BMD was equivocal, but n-3 FA
      supplement use was significantly associated with higher spine BMD - a finding
      that deserves further study. INTRODUCTION: Associations between polyunsaturated
      fatty acids and bone mineral density are not well understood. PURPOSE: To
      evaluate the cross-sectional relation between dietary omega 3 fatty acid intake
      (specifically docosahexaenoic acid, eicosapentaenoic acid, and
      octadecatetraenoic) and BMD at the hip and spine among older adults. METHODS:
      Omega 3 FA intake (g/day) was assessed from two 24-h recalls using the National
      Health and Nutrition Examination Survey (NHANES, in 2005-2008); and omega 3 FA
      supplement use (yes/no) via questionnaire. Multivariable regression models were
      developed to explain variance in femoral neck, total femur, and lumbar spine BMD
      among 2,125 men and women over 60 years. RESULTS: Mean age was 70 years. In
      adjusted models, dietary omega 3 FA were marginally associated with greater
      femoral neck BMD (p = 0.0505), but not with total femur BMD (p = 0.95) or lumbar
      spine BMD (p = 0.74). Omega 3 supplement use was significantly positively
      associated with lumbar spine BMD (p = 0.005) but not with femoral neck or total
      femur BMD. CONCLUSIONS: Dietary intakes of omega 3 FA were marginally associated
      with femoral neck BMD; however, omega 3 supplement use was significantly
      associated with higher lumbar spine BMD in older adults. These results emphasize
      the need for assessment of total omega 3 intakes (diet and supplements) to
      provide a greater range of intake and a more accurate picture of the relation
      between omega 3 FA and BMD.

PMID- 24121999
TI  - Use of a performance algorithm improves utilization of vertebral fracture
      assessment in clinical practice.
AB  - SUMMARY: A performance algorithm can be successfully used by bone density
      technologists at the time of a bone density test to identify patients with an
      indication for vertebral fracture assessment (VFA). Doing so appropriately
      increases physician prescription of fracture prevention medication. INTRODUCTION:
      Densitometric spine imaging (vertebral fracture assessment, VFA) can identify
      prevalent vertebral fracture but is underutilized. We developed an algorithm by
      which DXA technologists identify patients for whom VFA should be performed.
      Following this algorithm, VFA was performed in patients whose lowest T-score
      (lumbar spine, total hip, or femoral neck) was between -1.5 and -2.4 inclusive
      and with one of the following: age, >= 65 years; height loss, >= 1.5 in.; or
      current systemic glucocorticoid therapy. Our main objectives were to assess
      change in VFA utilization at two other healthcare organizations after algorithm
      implementation, and to estimate the association of VFA results with prescription
      of fracture prevention medication. METHODS: The proportions of patients with an
      indication for VFA who had one performed before and after algorithm
      implementation were compared. Logistic regression was used to estimate the
      multivariable-adjusted association of VFA results with subsequent prescription of
      fracture prevention medication adjusted for healthcare organization (study site).
      RESULTS: After algorithm introduction, appropriate VFA use rose significantly
      Patients with a VFA positive for vertebral fracture had an odds ratio of 3.2 (95
      % C.I., 2.1- 5.1) for being prescribed new fracture prevention medication,
      adjusted for age, sex, prior clinical fracture, use of glucocorticoid medication,
      femoral neck bone mineral density T-score, and study site. CONCLUSIONS: An
      algorithm to identify those for whom VFA is indicated can successfully be
      implemented by DXA technologists. Documentation of vertebral fracture increases
      prescription of fracture prevention medication for patients who otherwise lack an
      apparent indication for such therapy.

PMID- 24122000
TI  - An alternative injection technique for performing MR ankle arthrography: the
      lateral mortise approach.
AB  - OBJECTIVES: This study evaluates whether the recently described lateral mortise
      (LM) approach to therapeutic ankle injections can also be used to inject the
      ankle prior to magnetic resonance arthrography (MRA) without impairing the
      evaluation of the anterior talofibular ligament (ATFL). MATERIALS AND METHODS: An
      IRB-approved, retrospective review of ankle MRAs performed using the LM approach
      between April 2009 and April 2011 was conducted. The MRAs were independently
      evaluated by three musculoskeletal radiologists for: ATFL assessment (well
      assessed, limited or unable to assess), amount of fluid in the anterolateral soft
      tissues (none to large), and capsular distention (underdistended to
      overdistended). Patient age, gender, fluoroscopy time, injection location, degree
      of ankle arthritis, and ankle joint narrowing on radiographs were recorded.
      Statistical analysis was performed using exact binomial confidence limits.
      RESULTS: Fifteen MRAs were successfully performed on 13 patients (mean age: 27
      years, 11 male, 2 female). Mean fluoroscopic time was 39 s (range 9-108) and mean
      volume injected was 7 mL (range 5-9 mL). The ATFL was well assessed on all MRAs.
      A moderate to large amount of fluid was noted in the anterolateral soft tissues
      on 5 out of 15 MRAs. No ankle joints were underdistended, but 3 out of 15 were
      overdistended. CONCLUSION: Since the ATFL is inferior to the location used for
      the LM injection, the interpretation of the ankle MRA, specifically ATFL
      evaluation, was not compromised in any patient. Therefore, the LM approach can be
      used as an alternative to the anteromedial approach for ankle MRA without
      sacrificing diagnostic quality.

PMID- 24122001
TI  - MR versus MR arthrography in detection of supraspinatus tendon tears in patients
      without previous shoulder surgery.
AB  - PURPOSE: We report the prevalence of supraspinatus tendon tears seen on MR
      arthrography that are not seen on conventional MR exam in the same patient
      population. MATERIALS AND METHODS: A total of 150 consecutive conventional
      shoulder MR and MR arthrography exams performed on the same patients who went on
      to arthroscopy were reviewed retrospectively by consensus reading of two
      musculoskeletal radiologists. Full-thickness supraspinatus tendon tears were
      assessed. None of the patients had previous shoulder surgery. RESULTS: There were
      113 full-thickness supraspinatus tendon tears seen on conventional MR exam while
      there were 119 full-thickness supraspinatus tendon tears seen on MR arthrography.
      The six additional full-thickness supraspinatus tendon tears seen on MR
      arthrography but not seen on conventional MR exam were confirmed at arthroscopy.
      CONCLUSIONS: Some full-thickness supraspinatus tendon tears are not seen on
      conventional MR exam but are seen on MR arthrography. This is most likely due to
      fibrosis at the supraspinatus tendon tear site simulating an intact tendon on
      conventional MR.

PMID- 24122002
TI  - Chemotherapy for anaplastic thyroid cancer using docetaxel and cisplatin: report
      of eight cases.
AB  - Anaplastic thyroid carcinoma has a dismal prognosis and lacks an established
      therapeutic strategy. We have recently conducted chemotherapy with docetaxel and
      cisplatin as part of multimodal treatment for eight patients with anaplastic
      thyroid carcinoma. Docetaxel (75 mg/m2) and cisplatin (75 mg/m2) were
      administered on day 1 every 4 weeks for six courses. This chemotherapy was used
      as induction therapy in one patient, as therapy for distant metastases in five
      patients and as postoperative adjuvant therapy in two patients. Three patients
      showed partial responses and three patients showed stable disease. After
      excluding the two patients receiving the treatment as adjuvant therapy the
      response rate was 50 %. Grade 3 or 4 leukocytopenia occurred in seven patients
      (88 %), but these adverse events were tolerable. Chemotherapy with docetaxel and
      cisplatin may thus be feasible for anaplastic thyroid carcinoma.

PMID- 24122003
TI  - Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular
      stroke therapy.
AB  - OBJECTIVE: Immune dysregulation influences outcome following acute ischemic
      stroke (AIS). Admission white blood cell (WBC) counts are routinely obtained,
      making the neutrophil-lymphocyte ratio (NLR) a readily available biomarker of the
      immune response to stroke. This study sought to identify the relationship between
      NLR and 90 day AIS outcome. METHODS: A retrospective analysis was performed on
      patients who underwent endovascular therapy for AIS at West Virginia University
      Hospitals, Morgantown, West Virginia. Admission WBC differentials were analyzed
      as the NLR. Stroke severity was measured by the National Institutes of Health
      Stroke Scale (NIHSS) score and outcome by the modified Rankin Scale (mRS) score
      at 90 days. Univariate relationships between NLR, age, NIHSS, and mRS were
      established by correlation coefficients; the t test was used to compare NLR with
      recanalization and stroke location (anterior vs posterior). Logistic regression
      models were developed to identify the ability of NLR to predict mRS when
      controlling for age, recanalization, and treatment with IV tissue plasminogen
      activator (tPA). RESULTS: 116 patients were reviewed from 2008 to 2011. Mean age
      of the sample was 67 years, and 54% were women. Mean baseline NIHSS score was 17
      and 90 day mRS score was 4. There was a significant relationship between NLR and
      mRS (p=0.02) that remained when controlling for age, treatment with IV tPA, and
      recanalization. NLR >=5.9 predicted poor outcome and death at 90 days.
      CONCLUSIONS: This study shows that the NLR, a readily available biomarker, may be
      a clinically useful tool for risk stratification when evaluating AIS patients as
      candidates for endovascular therapies.

PMID- 24122004
TI  - Reducing radiation dose while maintaining diagnostic image quality of cerebral
      three-dimensional digital subtraction angiography: an in vivo study in swine.
AB  - BACKGROUND: Three-dimensional digital subtraction angiography (3D-DSA) is a
      modern technique that allows for better appreciation of complex vascular lesions.
      This study evaluates the impact of various dose reduction strategies on 3D-DSA
      image quality. METHODS: The standard manufacturer 5 s 0.36 MUGy/frame setting was
      modified to create lower dose 3D-DSA protocols by varying the acquisition time (5
      or 3 s) and/or dose per frame (0.36, 0.24, 0.17, and 0.10 MUGy/f). All protocols
      were evaluated in three swine. Four raters measured a segment of the external
      carotid artery on two-dimensional multiplanar reconstruction images. The raters
      were also presented with three-dimensional volume rendered images from all
      protocols in a blinded manner and asked to choose the superior image. A full
      model analysis of variance with repeated measure factors was performed to compare
      mean differences in measurements between protocols. RESULTS: Measurement
      differences between the standard and low dose protocols were not clinically
      significant (<0.5 mm). All raters demonstrated high inter-rater reliability. The
      5 s protocols were considered as qualitatively superior to the 3 s protocols.
      Delivered system doses ranged from 43.8 to 6.5 mGy. The 5 s 0.10 MUGy/frame
      protocols generated 65-68% less delivered dose compared with the 5 s 0.36
      MUGy/frame setting. CONCLUSIONS: Low dose 3D-DSA protocols with preserved image
      quality are achievable, and can help reduce unnecessary radiation exposure to
      both patients and operators. The 5 s low dose protocols generated clinically
      acceptable and superior images compared with the 3 s protocols, suggesting a more
      important role for acquisition time than dose per frame to maintain image
      quality.

PMID- 24122005
TI  - Elevated [Ca2+]i levels occur with decreased calpain activity in aged fibroblasts
      and their reversal by energy-rich compounds: new paradigm for Alzheimer's disease
      prevention.
AB  - Elevated intracellular Ca2+ levels in the aging brain are widely thought to
      hyperactivate Ca2+ signaling and Ca2+-dependent enzymes, leading to neuronal
      death through an excitatory mechanism in Alzheimer's disease (AD). This "Ca2+
      overload" hypothesis has been questioned by our theoretical analyses. To better
      understand the relationship between the "level" and functionality of Ca2+ in
      aging, in this study we simultaneously measured intracellular Ca2+ transients and
      calpain activity in cultured human fibroblasts. We found that Ca2+ transitions
      elicited by bradykinin were indeed overstayed or elevated in levels in old cells
      but, remarkably, calpain activity was decreased compared to young cells. Also,
      treating young cells with the energy inhibitor rotenone or with H2O2
      recapitulated the Ca2+ overstay and calpain inactivation found in old cells. More
      importantly, treating old cells with high-energy compounds such as phosphoenol
      pyruvate or phosphocreatine, which boosted cellular ATP content, reduced the Ca2+
      overstay and re-activated calpain. Moreover, Ca2+ levels and calpain activity
      were dramatically raised in the dying cells killed by detergent. Finally, Ca2+
      oscillations induced by low dose of bradykinin in old cells exhibited lower spike
      frequency, but higher overall levels. Collectively, these results suggest that
      (a) Ca2+ overload in old cells arises from an inefficient Ca2+ handling system
      compromised by age-related energy depletion and oxidative stress; and (b) despite
      elevated levels, the functionality of Ca2+ signaling has diminished in old cells.
      Thus, the study reinforces the concept that tonic promotion of bioenergetics and
      Ca2+ signaling function is a reasonable and new paradigm to protect the aging
      brain cells to prevent AD. 

PMID- 24122007
TI  - Ascorbic-acid-assisted growth of high quality M@ZnO: a growth mechanism and
      kinetics study.
AB  - We present a general route for synthesizing M@ZnO nanoparticles (NPs) by using
      ascorbic acid (AA) to induce deposition of ZnO on various shaped and structured
      cationic-surfactant-capped NP surfaces (noble, magnetic, semiconductor, rod-like,
      spherical, cubic, dendrite, alloy, core@shell). The results show that the
      complexing (AA and Zn(2+)) and cooperative effects (AA and CTAB) play important
      roles in the formation of polycrystalline ZnO shells. Besides, the growth
      kinetics of M@ZnO was systematically studied. It was found that the slow growth
      rate favors the successful formation of uniform core@ZnO NPs with relatively
      loose shells. An appropriate growth rate allows achieving high quality M@ZnO NPs
      with dense shells. However, very fast growth causes significant additional
      nucleation and the formation of pure ZnO NPs. This general method is suitable for
      preparing M@ZnO using seed NPs prepared in both water and organic phases. It
      might be an alternative route for functionalizing NPs for bioapplications (ZnO is
      biocompatible), modulating material properties as designed, or synthesizing
      template materials for building other nanostructures. 

PMID- 24122006
TI  - Telomere-end processing: mechanisms and regulation.
AB  - Telomeres are specialized nucleoprotein complexes that provide protection to the
      ends of eukaryotic chromosomes. Telomeric DNA consists of tandemly repeated G
      rich sequences that terminate with a 3' single-stranded overhang, which is
      important for telomere extension by the telomerase enzyme. This structure, as
      well as most of the proteins that specifically bind double and single-stranded
      telomeric DNA, are conserved from yeast to humans, suggesting that the mechanisms
      underlying telomere identity are based on common principles. The telomeric 3'
      overhang is generated by different events depending on whether the newly
      synthesized strand is the product of leading- or lagging-strand synthesis. Here,
      we review the mechanisms that regulate these processes at Saccharomyces
      cerevisiae and mammalian telomeres.

PMID- 24122008
TI  - MicroRNAs are involved in the self-renewal and differentiation of cancer stem
      cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules, whose primary function is
      to regulate gene expression at the post-transcriptional/translational levels.
      MiRNAs play crucial roles in normal biological processes and are commonly dys
      regulated in human diseases. Stem cells are regarded as the "mother" cells of all
      types of differentiated cells that comprise tissues and organs of the body. A
      novel hypothesis proposes that tumors are composed of heterogeneous cells derived
      from cancer stem cells, which have self-renewal and differentiation capabilities
      similar to those of normal stem cells. Cancer stem cells have been isolated and
      characterized from various tumors. Given recent studies supporting the critical
      regulatory roles of miRNAs in the self-renewal and differentiation of cancer stem
      cells, better understanding the functions of miRNAs will provide invaluable
      insights into the prevention of tumorigenesis and tumor progression. In this
      review, we will summarize the research progress in the study of miRNAs involved
      in the self-renewal and differentiation of cancer stem cells. 

PMID- 24122009
TI  - Age-dependent contribution of Rho kinase in carbachol-induced contraction of
      human detrusor smooth muscle in vitro.
AB  - AIM: Activation of muscarinic receptors on the detrusor smooth muscle is followed
      by contraction, which involves both myosin light chain kinase (MLCK) and Rho
      kinase (ROCK). The aim of this study was to determine the relative contributions
      of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle
      in vitro. METHODS: Detrusor smooth muscle strips were prepared from the
      macroscopically unaffected bladder wall of patients underwent cystectomy. The
      strips were fixed in an organ bath, and carbachol or KCl-induced isometric
      contractions were measured by force transducers. RESULTS: Addition of carbachol
      (0.4-4 MUmol/L) into the bath induced concentration-dependent contractions of
      detrusor specimens, which was completely abolished by atropine (1 MUmol/L). Pre
      incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK
      inhibitors HA1100 and Y-27632 (each at 10 MUmol/L) significantly blocked
      carbachol-induced contractions as compared to the time-control experiments.
      Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol
      induced contractions. The residual carbachol-induced contractions in the presence
      of both MLCK and ROCK inhibitors were significantly smaller than the contractions
      obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an
      additive effect of the two kinases. Interestingly, ROCK-mediated carbachol
      induced contractions were positively correlated to the age of patients (r=o.52,
      P<0.05). CONCLUSION: Both MLCK and ROCK contribute to carbachol-induced
      contractions of human detrusor smooth muscle. ROCK inhibitors may be a new
      pharmacological approach to modulate human bladder hyperactivity.

PMID- 24122010
TI  - Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following
      resuscitated hemorrhagic shock in rats.
AB  - AIM: To investigate the protective effects of hydrogen sulfide (H2S) against
      inflammation, oxidative stress and apoptosis in a rat model of resuscitated
      hemorrhagic shock. METHODS: Hemorrhagic shock was induced in adult male SD rats
      by drawing blood from the femoral artery for 10 min. The mean arterial pressure
      was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were
      observed for 200 min, and then killed. The lungs were harvested and
      bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were
      examined using Western blotting and immunohistochemical analyses. NaHS (28
      MUmol/kg, ip) was injected before the resuscitation. RESULTS: Resuscitated
      hemorrhagic shock induced lung inflammatory responses and significantly increased
      the levels of inflammatory cytokines IL-6, TNF-alpha, and HMGB1 in
      bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused
      marked oxidative stress in lung tissue as shown by significant increases in the
      production of reactive oxygen species H2O2 and .OH, the translocation of Nrf2, an
      important regulator of antioxidant expression, into nucleus, and the decrease of
      thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly
      increased the expression of death receptor Fas and Fas-ligand and the number
      apoptotic cells in lung tissue, as well as the expression of pro-apoptotic
      proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the
      expression of Bcl-2. Injection with NaHS significantly attenuated these
      pathophysiological abnormalities induced by the resuscitated hemorrhagic shock.
      CONCLUSION: NaHS administration protects rat lungs against inflammatory responses
      induced by resuscitated hemorrhagic shock via suppressing oxidative stress and
      the Fas/FasL apoptotic signaling pathway.

PMID- 24122012
TI  - 3D-QSAR and 3D-QSSR studies of thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as
      CDK4 inhibitors by CoMFA analysis.
AB  - AIM: To investigate the structural basis underlying potency and selectivity of a
      series of novel analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones as cyclin
      dependent kinase 4 (CDK4) inhibitors and to use this information for drug design
      strategies. METHODS: Three-dimensional quantitative structure-activity
      relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity
      relationship (3D-QSSR) models using comparative molecular field analysis (CoMFA)
      were conducted on a training set of 48 compounds. Partial least squares (PLS)
      analysis was employed. External validation was performed with a test set of 9
      compounds. RESULTS: The obtained 3D-QSAR model (q(2)=0.724, r(2)=0.965,
      r(2)pred=0.945) and 3D-QSSR model (q(2)=0.742, r(2)=0.923, r(2)pred=0.863) were
      robust and predictive. Contour maps with good compatibility to active binding
      sites provided insight into the potentially important structural features
      required to enhance activity and selectivity. The contour maps indicated that
      bulky groups at R1 position could potentially enhance CDK4 inhibitory activity,
      whereas bulky groups at R3 position have the opposite effect. Appropriate
      incorporation of bulky electropositive groups at R4 position is favorable and
      could improve both potency and selectivity to CDK4. CONCLUSION: These two models
      provide useful information to guide drug design strategies aimed at obtaining
      potent and selective CDK4 inhibitors.

PMID- 24122011
TI  - Acute exposure of methylglyoxal leads to activation of KATP channels expressed in
      HEK293 cells.
AB  - AIM: Highly reactive carbonyl methylglyoxal (MGO) is one of the metabolites
      excessively produced in diabetes. We have showed that prolonged exposure of
      vascular smooth muscle cells to MGO leads to instability of the mRNA encoding ATP
      sensitive potassium (KATP) channel. In the present study we investigated the
      effects of MGO on the activity of KATP channels. METHODS: Kir6.1/ SUR2B,
      Kir6.2/SUR2B or Kir6.2Delta36 (a truncated Kir6.2 isoform) alone was expressed in
      HEK293 cells. Whole-cell currents were recorded in the cells with an Axopatch
      200B amplifier. Macroscopic currents and single-channel currents were recorded in
      giant inside-out patches and normal inside-out patches, respectively. Data were
      analyzed using Clampfit 9 software. RESULTS: The basal activity of Kir6.1/SUR2B
      channels was low. The specific KATP channel opener pinacidil (10 MUmol/L) could
      fully activate Kir6.1/SUR2B channels, which was inhibited by the specific KATP
      channel blocker glibenclamide (10 MUmol/L). MGO (0.1-10 mmol/L) dose-dependently
      activated Kir6.1/SUR2B channels with an EC50 of 1.7 mmol/L. The activation of
      Kir6.1/SUR2B channels by MGO was reversible upon washout, and could be inhibited
      completely by glibenclamide. Kir6.2Delta36 channels expressed in HEK293 cells
      could open automatically, and the channel activity was enhanced in the presence
      of MGO (3 mmol/L). Single channel recordings showed that MGO (3 mmol/L) markedly
      increased the open probability of Kir6.1/SUR2B channels, leaving the channel
      conductance unaltered. CONCLUSION: Acute application of MGO activates KATP
      channels through direct, non-covalent and reversible interactions with the Kir6
      subunits.

PMID- 24122013
TI  - Hypoxia/oxidative stress alters the pharmacokinetics of CPU86017-RS through
      mitochondrial dysfunction and NADPH oxidase activation.
AB  - AIM: Hypoxia/oxidative stress can alter the pharmacokinetics (PK) of CPU86017-RS,
      a novel antiarrhythmic agent. The aim of this study was to investigate the
      mechanisms underlying the alteration of PK of CPU86017-RS by hypoxia/oxidative
      stress. METHODS: Male SD rats exposed to normal or intermittent hypoxia (10% O2)
      were administered CPU86017-RS (20, 40 or 80 mg/kg, ig) for 8 consecutive days.
      The PK parameters of CPU86017-RS were examined on d 8. In a separate set of
      experiments, female SD rats were injected with isoproterenol (ISO) for 5
      consecutive days to induce a stress-related status, then CPU86017-RS (80 mg/kg,
      ig) was administered, and the tissue distributions were examined. The levels of
      Mn-SOD (manganese containing superoxide dismutase), endoplasmic reticulum (ER)
      stress sensor proteins (ATF-6, activating transcription factor 6 and PERK, PRK
      like ER kinase) and activation of NADPH oxidase (NOX) were detected with Western
      blotting. Rat liver microsomes were incubated under N2 for in vitro study.
      RESULTS: The Cmax, t1/2, MRT (mean residence time) and AUC (area under the curve)
      of CPU86017-RS were significantly increased in the hypoxic rats receiving the 3
      different doses of CPU86017-RS. The hypoxia-induced alteration of PK was
      associated with significantly reduced Mn-SOD level, and increased ATF-6, PERK and
      NOX levels. In ISO-treated rats, the distributions of CPU86017-RS in plasma,
      heart, kidney, and liver were markedly increased, and NOX levels in heart,
      kidney, and liver were significantly upregulated. Co-administration of the NOX
      blocker apocynin eliminated the abnormalities in the PK and tissue distributions
      of CPU86017-RS induced by hypoxia/oxidative stress. The metabolism of CPU86017-RS
      in the N2-treated liver microsomes was significantly reduced, addition of N
      acetylcysteine (NAC), but not vitamin C, effectively reversed this change.
      CONCLUSION: The altered PK and metabolism of CPU86017-RS induced by
      hypoxia/oxidative stress are produced by mitochondrial abnormalities, NOX
      activation and ER stress; these abnormalities are significantly alleviated by
      apocynin or NAC.

PMID- 24122015
TI  - ESPN Course 2013-the trainee's point of view.

PMID- 24122014
TI  - Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin.
AB  - Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine
      as a tonic herb that provides many beneficial effects. Pharmacologic studies in
      the last decades have shown that ginsenosides (ginseng saponins) are primarily
      responsible for the actions of ginseng. However, the effects of ginseng are not
      fully explained by ginsenosides. Recently, another class of active ingredients
      called gintonin was identified. Gintonin is a complex of glycosylated ginseng
      proteins containing lysophosphatidic acids (LPAs) that are the intracellular
      lipid mitogenic mediator. Gintonin specifically and potently activates the G
      protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now
      also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng
      pharmacology and LPA therapeutics. In the present review, we evaluate the
      pharmacology of ginseng with the traditional viewpoint of Yin and Yang
      components. Furthermore, we will compare ginsenoside and gintonin based on the
      modern view of molecular pharmacology in terms of ion channels and GPCRs. 

PMID- 24122016
TI  - Growing teratoma syndrome in intracranial non-germinomatous germ cell tumors
      (iNGGCTs): a risk for secondary malignant transformation-a report of two cases.
AB  - PURPOSE: About 5% of pediatric intracranial germ cell tumors and 20% of non
      germinomatous germ cell tumors (NGGCT) progress to growing teratoma syndrome
      (GTS) following chemoradiotherapy. The growing teratoma is thought to arise from
      the chemotherapy-resistant, teratomatous portion of a germ cell tumor and is
      commonly benign but may undergo malignant transformation. METHODS: Two pediatric
      patients whose intracranial NGGCTs progressed to growing teratomas during
      chemotherapy and later transformed to secondary malignant tumors after partial
      resection and radiation therapy (RT). RESULTS: Both tumors were diagnosed by MRI
      scans and elevated serum and CSF markers. Following normalization of tumor
      markers with chemotherapy and initial decrease in tumor volume, subsequent
      imaging showed regrowth during chemotherapy with pathology revealing benign
      teratoma. RT was administered. Several years following this treatment, further
      growth was seen with pathology indicating malignant carcinoma in one patient and
      malignant rhabdomyosarcoma in the other. The patient with carcinoma received
      palliative care while the patient with the sarcoma received further resection,
      intensive chemotherapy, and an autologous stem cell transplant and is currently
      in remission, 36 months since malignant transformation. CONCLUSION: Malignant
      transformation of presumed residual teratoma has been seldom reported. Treatment
      of NGGCT involves platinum-based chemotherapy with craniospinal RT and boost to
      the primary site, with cure rates of around 80%. Teratomas are characteristically
      chemotherapy and RT resistant and are treated surgically. In the event that
      residual or growing teratoma is suspected, a complete resection should be
      considered early in the management as there is a risk of malignant transformation
      of residual teratoma.

PMID- 24122017
TI  - Hypertrophic olivary degeneration with gadolinium enhancement after posterior
      fossa surgery in a child with medulloblastoma.
AB  - Hypertrophic olivary degeneration (HOD) is a rare transsynaptic form of
      degeneration occurring secondary to the disruption of the dentato-rubro-olivary
      pathway ("Guillain-Mollaret triangle"). HOD can be caused by ischemic,
      hemorrhagic, traumatic, or neoplastic lesions, and it can also occur following
      posterior fossa surgery. MRI characteristics of HOD include T2 signal increase
      and hypertrophy. To date, blood-brain barrier disruption has not been reported in
      HOD. Here, we present the first case of HOD with temporary gadolinium enhancement
      in a 10-year-old child 7 months after resection of a posterior fossa
      medulloblastoma. The recognition of gadolinium enhancement as a radiological
      feature of HOD may help to distinguish between this benign secondary condition
      and tumor recurrence.

PMID- 24122018
TI  - Normative data for fetal cisterna magna length measurement between 18 and 24
      weeks of pregnancy.
AB  - PURPOSE: The aim of this study was to determine normative data for fetal cisterna
      magna length (CML) measurement in a Brazilian population. METHODS: This was a
      retrospective cross-sectional study on 3,862 normal singleton pregnancies between
      the 18th and 24th weeks of pregnancy. Fetal CML was measured in the axial plane
      of the fetal head, at lateral ventricle level, including the cavum septum
      pellucidum, thalamus, third ventricle, and transverse cerebellar diameter. The
      anteroposterior measurement was made between the posterior border of the
      cerebellar vermis and the internal face of the occipital bone. To assess the
      correlation between CML and gestational age (GA), polynomial equations were
      calculated, with adjustments using determination coefficient (R2). RESULTS: The
      mean CML ranged from 4.29+/-0.93 mm at 18 to 18+6 weeks to 5.58+/-1.23 mm at 24
      to 24+6 weeks of pregnancy. There was a good correlation between CML and GA, best
      represented by a linear equation: CML=0.535+0.208*GA (R2=0.084). CONCLUSION: We
      established normative data for fetal CML in the second trimester of pregnancy, in
      a large Brazilian population.

PMID- 24122019
TI  - Establishing construct and predictive validity of the prison inmate inventory for
      use with female inmates.
AB  - This study establishes the validity of the Prison Inmate Inventory for use among
      female inmates (N = 628). Contrast groups were used to establish construct
      validity; negative binomial regression analysis was used to confirm predictive
      validity. Female inmates who were arrested at a younger age demonstrated more
      severe problems with violence, antisocial traits, distress, adjustment to prison
      life, and judgment. Results from the negative binomial analysis revealed that
      inmate risk (low and severe) predicted expected counts of probation revocations,
      parole revocation, and escape attempts. Expected counts were not related to
      race/ethnicity in this sample. 

PMID- 24122020
TI  - Narrative beyond prison gates: contradiction, complexity, and reconciliation.
AB  - This article reports on qualitative research with Alan, a former resident of the
      therapeutic communities at Her Majesty's Prison (HMP) Grendon, England, exploring
      narrative identity beyond therapy. The study emphasises the complexity inherent
      in the five identities on which Alan draws-the Achiever, the Liminal Man, the
      Lucky Man, the Puppet, and the Wise Man. We suggest that narrative identities are
      adapted and reconstructed as they are taken outside of the therapeutic community
      into a less supportive social environment. This process continues to present
      challenges for the ex-resident, who may struggle to reconcile the redemptive
      identities nurtured in therapy with condemnatory ones that have echoes of a
      criminal past, which may be reignited by personal and social circumstances. 

PMID- 24122022
TI  - Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours.
AB  - Mammary tumours are the most common tumour type in female dogs. The formation of
      the mammary tumours is multifactorial but the high incidence of tumour disease in
      certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are
      the most important genes significantly associated with mammary tumours. The aim
      of this study was to determine the association between the variations of these
      two genes and canine mammary tumours. 5'-untranslated region, intron 8 and exon 9
      of BRCA1 and exons 12, 24, 27 of BRCA2 were sequenced in order to detect the
      genetic variations. In addition to six previously identified polymorphisms, six
      novel single nucleotide polymorphisms (SNPs) were detected. Five of the coding
      SNPs were synonymous and three of them were non-synonymous. The comparison of the
      sequences from 25 mammary tumour bearing and 10 tumour free dogs suggested that
      the two SNPs in intron 8 and exon 9 of BRCA1 and two SNPs in exon 24 and exon 27
      of BRCA2, which are firstly identified in this study, might be associated with
      mammary tumour development in dogs. Especially one SNP in exon 9 of BRCA1 and one
      SNP in exon 24 of BRCA2 were found to be significantly associated with canine
      mammary tumours. 

PMID- 24122023
TI  - Effect of minocycline on pentylenetetrazol-induced chemical kindled seizures in
      mice.
AB  - Inflammation is one of the mechanisms involved in seizure induction. In this
      study, the effect of minocycline, an anti-inflammatory drug, was investigated on
      kindling acquisition. Chemical kindling was induced by injection of a
      subthreshold dose of pentylenetetrazol (PTZ; 37.5 mg/kg) in mice on every other
      day. Two groups of animals received minocycline (25 mg/kg) at 1 h before or 1 h
      after PTZ injection. Following the last PTZ injection, the changes in gene
      expression of TNF-alpha receptor, gamma2 subunit of GABAA receptor and NR2A
      subunit of NMDA receptor were assessed in the hippocampus and piriform cortex.
      Injection of minocycline before PTZ increased the latency to stage 4 seizure, and
      decreased the duration of stages 4 and 5 seizure. It also prevented the increase
      in the mRNA of NR2A subunit of NMDA receptor in the hippocampus and removed the
      PTZ-induced increase in mRNA of gamma2 subunit of GABAA receptor in piriform
      cortex of PTZ kindled mice. Minocycline also prevented the increase in TNF-alpha
      receptor gene expression in both hippocampus and piriform cortex. Injection of
      minocycline after PTZ had no significant effect on measured parameters.
      Therefore, it can be concluded that minocycline may exert an anticonvulsant
      effect through preventing the increase in GABAA and NMDA receptor subunits. These
      effects are accompanied by a reduction in an important inflammation index, TNF
      alpha receptor. 

PMID- 24122024
TI  - Racial and ethnic disparities in stroke subtypes: a multiethnic sample of
      patients with stroke.
AB  - Stroke subtypes have been reported to differ by race and ethnic subgroups and
      have not been adequately explained. We aim to evaluate if the prevalence of
      vascular risk factors accounts for differences observed in stroke subtypes by
      race/ethnicity. Patients with acute stroke were prospectively enrolled in the
      Miami Stroke Registry. Patients' demographic, clinical and radiological
      characteristics were systematically collected. Stroke subtypes were ascertained
      using TOAST criteria. The sample was divided into Non-Hispanic Whites (NHW),
      Hispanics, African Americans (AA), and Non-Hispanic Black Caribbean (NHBC).
      Univariable and multivariable logistic regression analyses were performed to
      assess differences among groups. Among 473 stroke patients (mean age 64 +/- 14
      years; 63.7% were men) of which 52.9% were Hispanic, 22.6% were AA, 13.5% NHBC
      and 11.0% were NHW. Large artery atherosclerosis was more prevalent in NHBC (OR
      1.74, 95% CI 1.02-2.97) than in the other groups. Adjusting for covariates
      rendered the association not significant (OR 1.71, 95% CI 0.93-3.16).
      Cardioembolism was more frequent in Hispanics (OR 1.94, 95% CI 1.28-2.96) and NHW
      (OR 2.66, 95% CI 1.42-4.96) as compared to NHBC and AA combined. Adjusting for
      covariates, the association was no longer significant for Hispanics but was
      further strengthened for NHW (OR 3.02, 95% CI 1.42-6.42). Our results suggest
      that the vascular risk factors prevalence among different racial and ethnic
      groups partially explains disparities found in the prevalence of some stroke
      subtypes. Addressing health disparities remains an important public health aspect
      of stroke prevention.

PMID- 24122025
TI  - Treatment paradigms for pituitary adenomas: defining the roles  of radiosurgery
      and radiation therapy.
AB  - Pituitary adenomas represent one of the most common types of intracranial tumors.
      While their macroscopic appearance and anatomical location are relatively
      homogeneous, pituitary tumors have the potential to generate a wide variety of
      clinical sequelae. Treatment options for pituitary tumors include medical
      therapy, microscopic or endoscopic surgical resection, radiosurgery, radiation
      therapy, or observation depending on the biochemical profile and clinical status
      of the patient. Radiosurgery and external beam radiation therapy (EBRT) are most
      commonly as adjunctive treatments following incomplete surgical resection leaving
      residual tumor, tumor recurrence, or failure of medical therapy. We present a
      comprehensive literature review of the radiosurgery series for pituitary tumors
      including nonfunctioning adenomas, ACTH- and GH-secreting adenomas, and
      prolactinomas. While postradiosurgery radiographic tumor control for
      nonfunctioning adenomas is excellent, typically around 90 %, the rates of
      biochemical remission for functioning adenomas are lower than the tumor control
      rates. The highest endocrine remission rates are achieved patients with Cushing's
      disease and the lowest in those with prolactinomas. Although EBRT has been
      largely supplanted by radiosurgery for the vast majority of pituitary adenomas
      cases, there remains a role for EBRT in select cases involving large tumor
      volumes in close proximity to critical neural structures. By far the most common
      complication after radiosurgery or EBRT is delayed hypopituitarism followed by
      cranial neuropathies. The effect of suppressive medications on radiosurgery
      outcomes remains controversial. Due to the rare but well-documented occurrence of
      late recurrence following endocrine remission, long-term and rigorous clinical
      and radiographic follow-up is necessary for all pituitary adenoma patients
      treated with radiosurgery or EBRT.

PMID- 24122026
TI  - Statistics matter: data aggregation improves identification of community-level
      effects compared to a commonly used multivariate method.
AB  - The identification of the effects of toxicants on biological communities is
      hampered by the complexity and variability of communities. To overcome these
      challenges, the trait-based SPEAR approach has been developed. This approach is
      based on (i) identifying the vulnerable taxa using traits and (ii) aggregating
      these taxa into a group to reduce the between-replicate differences and scattered
      low-abundance distribution, both of which are typical for biological communities.
      This approach allows for reduction of the noise and determination of the effects
      of toxicants at low concentrations in both field and mesocosm studies. However,
      there is a need to quantitatively investigate its potential for mesocosm data
      evaluations and application in the ecological risk assessment of toxicants. In
      the present study, we analysed how the aggregation of the sensitive taxa can
      facilitate the identification of the effects. We used empirical data from a long
      term mesocosm experiment with stream invertebrates and an insecticide as well as
      a series of simulated datasets characterised by different degrees of data matrix
      saturation (corresponding to different sampling efforts), numbers of replicates,
      and between-replicate differences. The analyses of both the empirical and
      simulated data sets revealed that the taxa aggregation approach allows for the
      detection of effects at a lower saturation of the data matrices, smaller number
      of replicates, and higher between-replicate differences when compared to the
      multivariate statistical method redundancy analysis. These improvements lead to a
      higher sensitivity of the analysed systems, as long-term effects were detected at
      lower concentrations (up to 1,000 times). These outcomes suggest that methods
      based on taxa aggregation have a strong potential for use in mesocosm data
      evaluations because mesocosm studies are usually poorly replicated, have high
      between-replicate variability, and cannot be exhaustively sampled due to
      technical and financial constraints.

PMID- 24122021
TI  - Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI
      neurons of prefrontal cortex.
AB  - Cholinergic modulation of prefrontal cortex is essential for attention. In
      essence, it focuses the mind on relevant, transient stimuli in support of goal
      directed behavior. The excitation of prefrontal layer VI neurons through
      nicotinic acetylcholine receptors optimizes local and top-down control of
      attention. Layer VI of prefrontal cortex is the origin of a dense feedback
      projection to the thalamus and is one of only a handful of brain regions that
      express the alpha5 nicotinic receptor subunit, encoded by the gene chrna5. This
      accessory nicotinic receptor subunit alters the properties of high-affinity
      nicotinic receptors in layer VI pyramidal neurons in both development and
      adulthood. Studies investigating the consequences of genetic deletion of alpha5,
      as well as other disruptions to nicotinic receptors, find attention deficits
      together with altered cholinergic excitation of layer VI neurons and aberrant
      neuronal morphology. Nicotinic receptors in prefrontal layer VI neurons play an
      essential role in focusing attention under challenging circumstances. In this
      regard, they do not act in isolation, but rather in concert with cholinergic
      receptors in other parts of prefrontal circuitry. This review urges an
      intensification of focus on the cellular mechanisms and plasticity of prefrontal
      attention circuitry. Disruptions in attention are one of the greatest
      contributing factors to disease burden in psychiatric and neurological disorders,
      and enhancing attention may require different approaches in the normal and
      disordered prefrontal cortex.

PMID- 24122027
TI  - IgA deficiency and mortality: a population-based cohort study.
AB  - IgA deficiency has been linked to increased morbidity but data on mortality is
      lacking. In this population-based prospective cohort study we examined mortality
      in patients with IgA deficiency compared with the general population. Through six
      university hospitals in Sweden we identified 2,495 individuals with IgA
      deficiency (IgA deficiency <=0.07 mg/L) diagnosed between 1980 and 2012. Each
      patient with IgA deficiency was matched on age, sex, place of residence, and year
      of diagnosis with up to 10 general population controls (n = 24,509). Data on
      education level and emigration status were obtained from Statistics Sweden. Our
      main outcome measure was all-cause mortality retrieved from the nationwide Causes
      of Death Register, which includes >99 % of all deaths in Sweden. We used Cox
      regression to estimate mortality hazard ratios conditioned on the matching
      factors and adjusted for education level. During 25,367 person-years of follow-up
      (median 8.3), there were 260 deaths in the IgA deficiency group versus 1,599
      deaths during 257,219 person-years (median 8.6) in the general population
      controls (102 versus 62 deaths per 10,000 person-years; incidence rate
      difference, 40, 95%CI 28-53, P < .001). This corresponded to a conditional
      mortality hazard ratio of 1.8 (95%CI 1.6-2.1, P < .001). Relative mortality
      varied by follow-up time (P < .001) from a hazard ratio of 3.6 (95%CI 2.5-5.3; P
      < .001) during the first year to 1.9 (95%CI 1.5-2.4; P < .001) year 1-4; 1.9
      (95%CI 1.4-2.4; P < .001) year 5-9; 1.5 (1.0-2.2; P = .054) year 10-14.9; and 1.1
      (0.7-1.6; P = .66) year 15-25. Effect modification was also seen by age in each
      stratum of follow-up time, with higher relative mortality in younger than older
      patients (P < .001). In conclusion, patients with IgA deficiency are at increased
      risk of death in the first 10 to 15 years after diagnosis.

PMID- 24122028
TI  - Intracellular adenosine inhibits IgE-dependent degranulation of human skin mast
      cells.
AB  - PURPOSE: Adenosine (ADO) can enhance and inhibit mast cell degranulation.
      Potentiation of degranulation occurs at relatively low concentrations of ADO (10
      6-10-5 M) through triggering of A3AR, whereas, inhibition occurs at higher
      concentrations of ADO reportedly through triggering of A2aAR. However, the
      discrepancy in the concentration of ADO that inhibits degranulation and that
      required to trigger ADORs suggests a different mechanism. The purpose of this
      study is to determine the mechanism by which ADO inhibits human mast cell
      degranulation. METHODS: We compare the effectiveness of A2aAR specific antagonist
      ZM241385 and equilibrative nucleoside transporter inhibitors Dipyridamole and
      NBMPR in preventing ADO-mediated inhibition of FcepsilonRI-induced degranulation
      of human skin mast cells (hSMCs). Western blotting is done to analyze the effect
      of ADO on FcepsilonRI-induced Syk phosphorylation. RESULTS: Dipyridamole and
      NBMPR completely and dose-dependently prevented ADO from inhibiting FcepsilonRI
      induced degranulation in all hSMC preparations. In contrast, ZM241385 at 10-5 M
      was effective in only 3 of 10 hSMC preparations. Moreover, NBMPR was effective
      even in those hSMC preparations not responsive to ZM241385. ADO inhibited
      degranulation induced by FcepsilonRI crosslinking, but not that induced by
      complement component 5a (C5a), Substance P or calcium ionophore. Accordingly, ADO
      significantly attenuated FcepsilonRI-induced phosphorylation of Syk at the
      critical activating tyrosine (Y525). CONCLUSION: Blocking the influx of ADO, but
      not A2aAR signals, is necessary and sufficient to prevent ADO from inhibiting
      FcepsilonRI-induced mast cell degranulation. Thus, ADO specifically inhibits
      FcepsilonRI-induced degranulation of hSMCs primarily by an intracellular
      mechanism that requires its influx via equilibrative nucleoside transporter 1
      (ENT1).

PMID- 24122029
TI  - Clinical, immunological, and molecular characterization of hyper-IgM syndrome due
      to CD40 deficiency in eleven patients.
AB  - PURPOSE: Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare form of
      primary immunodeficiency with few reported cases. In this study, we further
      characterize the clinical, immunological, and molecular profiles of the disease
      in a cohort of 11 patients. METHODS: Molecular genetic analysis and a
      comprehensive clinical review of patients diagnosed with HIGM3 at our tertiary
      care center from 1994 to 2011 were undertaken. RESULTS: Eleven patients from
      seven families were enrolled. The patients had a median age of 9 years [ranging
      from 2 to 22 years old]. All 11 patients had recurrent chest infections at
      presentation. Pneumocystis jiroveci pneumonia was confirmed in three patients.
      Five patients had sclerosing cholangitis, and five patients had Cryptosporidium
      isolated from their stool. Six patients had nasal and sinus infections, and two
      of these patients had destructive nasal fungal infections. Eight patients had
      neutropenia. All of the patients had low IgG and normal or high IgM levels. IgA
      was undetectable in all but three patients. Two novel mutations were found: a
      splice site for intron 3 and a missense mutation located in the coding region of
      exon 3. Two patients underwent successful stem cell transplantation from a
      matched donor. Four patients are doing well on prophylaxis; two are very sick,
      one with protracted diarrhea and persistent Cryptosporidium and the other with
      neurological complications. Three patients died early in life as a result of
      severe sepsis. CONCLUSIONS: To our knowledge, this report provides the largest
      cohort of patients with this disease with a very long follow-up period. Our
      cohort showed variable disease severity

PMID- 24122030
TI  - Severe combined immunodeficiency (SCID) in Canadian children: a national
      surveillance study.
AB  - PURPOSE: Severe Combined Immune Deficiency (SCID) is universally fatal unless
      treated with hematopoietic stem cell transplantation (HSCT). Following the
      identification of disseminated Bacille Calmette-Guerin (BCG) infections in
      Canadian First Nations, Metis and Inuit (FNMI) children with unrecognized primary
      immune deficiencies, a national surveillance study was initiated in order to
      determine the incidence, diagnosis, treatment and outcome of children with SCID
      in Canada. METHODS: Canadian pediatricians were asked to complete a monthly
      reporting form if they had seen a suspected SCID case, from 2004 to 2010, through
      the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID
      criteria, more detailed data, including demographics and clinical information
      about investigations, treatment and outcome was collected. RESULTS: A total of 40
      cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI
      Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The
      proportion of SCID cases that were FNMI (17.5 %) was almost three times higher
      than was expected on the basis of proportion of the pediatric population
      estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per
      100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The
      mean age at diagnosis for all SCID cases was 4.2 months (range 1-583 days). There
      were 12 deaths (30 %; 95 % CI 18-46 %); seven died of confirmed or suspected
      infections before they could receive an HSCT. CONCLUSIONS: The frequency of SCID
      cases in FNMI children is higher than in the general Canadian pediatric
      population. The high mortality rate, due primarily to infection, suggests that
      early diagnosis by newborn screening followed by HSCT could significantly benefit
      children with SCID.

PMID- 24122032
TI  - Atomically-thick two-dimensional crystals: electronic structure regulation and
      energy device construction.
AB  - Atomically-thick two-dimensional crystals can provide promising opportunities to
      satisfy people's requirement of next-generation flexible and transparent
      nanodevices. However, the characterization of these low-dimensional structures
      and the understanding of their clear structure-property relationship encounter
      many great difficulties, owing to the lack of long-range order in the third
      dimensionality. In this review, we survey the recent progress in fine structure
      characterization by X-ray absorption fine structure spectroscopy and also
      overview electronic structure modulation by density-functional calculations in
      the ultrathin two-dimensional crystals. In addition, we highlight their structure
      property relationship, transparent and flexible device construction as well as
      wide applications in photoelectrochemical water splitting, photodetectors,
      thermoelectric conversion, touchless moisture sensing, supercapacitors and
      lithium ion batteries. Finally, we outline the major challenges and opportunities
      that face the atomically-thick two-dimensional crystals. It is anticipated that
      the present review will deepen people's understanding of this field and hence
      contribute to guide the future design of high-efficiency energy-related devices. 

PMID- 24122031
TI  - Exome sequencing reveals RAG1 mutations in a child with autoimmunity and sterile
      chronic multifocal osteomyelitis evolving into disseminated granulomatous
      disease.
AB  - We describe a boy who developed autoinflammatory (chronic sterile multifocal
      osteomyelitis) and autoimmune (autoimmune cytopenias; vitiligo) phenotypes who
      subsequently developed disseminated granulomatous disease. Whole exome sequencing
      revealed homozygous RAG1 mutations thus expanding the spectrum of combined
      immunodeficiency with autoimmunity and granuloma that can occur with RAG
      deficiency.

PMID- 24122033
TI  - Airway management in obese patient.
AB  - Oxygenation maintenance is the cornerstone of airway management in the obese
      patient related to anatomic and pathophysiologic issues. Difficult mask
      ventilation (DMV) risk is increased in obese patients according recognized
      predictors (Body Mass Index [BMI]>26 kg/m2, age >55 years, jaw protrusion
      severely limited, lack of teeth, snoring, beard, Mallampati class III or IV) and
      should systematically search. Difficult tracheal intubation (DTI) risk may be
      increased and risk should be assessed in a careful manner. Increased neck
      circumference and high BMI (>35 kg/m2) should be added to "standard" preoperative
      airway assessment including:Mallampati class, mouth opening and thyromental
      distance. In obese patients, preoxygenation is mandatory by 25 degrees  head-up
      position achieving better gas exchange than in supine position. In addition, to
      prevent early arterial oxygen desaturation related to a reduced functional
      residual capacity (FRC), atelectasis formation during anesthetic induction and
      after tracheal intubation, non invasive positive pressure ventilation and
      application of PEEP throughout this period are recommended. Airway management in
      obese patients has to consider: the anesthesia technique with maintenance or not
      of spontaneous ventilation, the available oxygenation technique in case of
      anticipated DMV, and the appropriate tracheal intubation technique (fiberoptic
      intubation technique or videolaryngoscope) according to the patient status and
      will. In unexpected difficult airway, the very first priority is oxygenation and
      a predefined strategy has to be implemented with oxygenation devices first
      (supraglottic devices or ILMA). Lastly, the final step of the obese airway
      management is tracheal extubation and recovery. A strategy with a fully awake
      patient, without residual paralysis, and a 25 degrees  head-up position is
      mandatory.

PMID- 24122034
TI  - Pneumonia in immunocompetent patients: combination antibiotic therapy.
AB  - Pneumonia's burden is still important worldwide not only because of its high
      incidence and mortality, but also for the elevated costs related to it. Despite
      the concerted efforts to reduce the incidence of sepsis-related complications,
      they continue to represent a major human and economic burden. The cornerstone of
      sepsis management is early appropriate empiric broad spectrum antibiotics,
      resuscitation, and source control. The association between inappropriate use of
      antibiotics and increased mortality is the rationale for the use of empiric
      antibiotic combination therapy in critically ill patients. The aim of this
      manuscript was to discuss recent literature regarding the management of severe
      pneumonia, both community-acquired and hospital-acquired/ventilator-associated,
      in critically ill patients. Use of combination therapy is warranted in severe
      infections with shock; considerations should be made on the importance of optimal
      antibiotic administration and adverse reactions, thus providing guidance for a
      rational use of antibiotics. 

PMID- 24122035
TI  - Clinical characteristics, hospital outcome and prognostic factors of patients
      with ventilator-related pneumothorax.
AB  - BACKGROUND: Mechanical ventilation is a common cause of iatrogenic pneumothorax
      in intensive care units (ICU). Most of the patients with ventilator-related
      pneumothorax (VRP) have underlying lung diseases and is associated with increased
      morbidity and mortality. The prognostic factors of VRP are not clear. The
      objective of this study was to find the possible prognostic factors. METHODS:
      Analysis of retrospectively collected data of patients with pneumothorax induced
      by mechanical ventilation. Data were obtained concerning demographics, acute
      physiology and chronic health evaluation (APACHE) II score, organ failure,
      underlying diseases, interval between the start of mechanical ventilation and
      pneumothorax, arterial blood gas, respiratory parameters and patient outcomes.
      RESULTS: One hundred and twenty-four patients with VRP were included for
      analysis. The incidence rate of VRP was 0.4% (124/31,660), and the mortality rate
      was 77.4%. The patients with VRP had higher hospital mortality rate than that of
      mechanically ventilated patients without pneumothorax (77.4% vs. 13.7%, P<0.001)
      or patient with procedure-related pneumothorax (77.4% vs. 29.4%, P<0.001). Most
      cases of VRP occurred in the early phase of mechanical ventilation, and 8.9% of
      the patients had a later episode of pneumothorax on the opposite lung. The
      interval between two episodes of VRP was short, at a median time of 2 days. Cox
      regression analysis showed that tension pneumothorax (P=0.001), PaO2/FiO2<200
      (P=0.002), and APACHE II score (P=0.008) were significantly associated with
      death. CONCLUSION: VRP patients with tension pneumothorax or PaO2/FiO2<200 had a
      higher risk of death. APACHE II scores were associated with mortality in the VRP
      patients with PaO2/FiO2>=200 mmHg.

PMID- 24122036
TI  - Chemotherapy-induced cardiovascular toxicity:  beyond anthracyclines.
AB  - It is not uncommon for anesthesiologists to encounter cancer patients who have
      received chemotherapy agents known to cause cardiovascular toxicities such as
      heart failure, systemic hypertension and thromboembolic events. Anthracyclines
      have been for several decades the most studied agents because of their known
      cardiovascular effects and relatively high incidence of heart failure. However,
      cancer patients are currently treated with newer chemotherapeutics such as
      imatinib, sunitinib, trastuzumab and bevacizumab that are also responsible of
      causing cardiovascular toxicities. The type of cardiotoxicity associated with
      these newer agents (type II cardiotoxicity) appears to be different in terms of
      pathogenesis to that caused by anthracyclines (type I cardiotoxicity). Thus,
      anesthesiologist needs to be aware of the clinical features of each type of
      cardiac toxicity. This review will summarize the current clinical evidence on
      cardiovascular toxicity induced by chemotherapeutic agents and will try to shed
      light on the current information regarding the perioperative management of
      patients with chemotherapy-induced cardiovascular toxicity.

PMID- 24122037
TI  - Neutral [2]rotaxane host systems that recognise halide anions in aqueous solvent
      mixtures.
AB  - Four pyridine N-oxide axle containing [2]rotaxanes have been synthesised via an
      anion templated threading-followed-by-stoppering strategy and shown to be the
      first examples of neutral interlocked host systems capable of recognising halide
      anions in aqueous solvent mixtures. 

PMID- 24122039
TI  - Formation of targeted monovalent quantum dots by steric exclusion.
AB  - Precise control over interfacial chemistry between nanoparticles and other
      materials remains a major challenge that limits broad application of
      nanotechnology in biology. To address this challenge, we used 'steric exclusion'
      to completely convert commercial quantum dots (QDs) into monovalent imaging
      probes by wrapping each QD with a functionalized oligonucleotide. We demonstrated
      the utility of these QDs as modular and nonperturbing imaging probes by tracking
      individual Notch receptors on live cells. 

PMID- 24122038
TI  - Genetically encoded fluorescent thermosensors visualize subcellular
      thermoregulation in living cells.
AB  - In mammals and birds, thermoregulation to conserve body temperature is vital to
      life. Multiple mechanisms of thermogeneration have been proposed, localized in
      different subcellular organelles. However, visualizing thermogenesis directly in
      intact organelles has been challenging. Here we have developed genetically
      encoded, GFP-based thermosensors (tsGFPs) that enable visualization of
      thermogenesis in discrete organelles in living cells. In tsGFPs, a tandem
      formation of coiled-coil structures of the Salmonella thermosensing protein TlpA
      transmits conformational changes to GFP to convert temperature changes into
      visible and quantifiable fluorescence changes. Specific targeting of tsGFPs
      enables visualization of thermogenesis in the mitochondria of brown adipocytes
      and the endoplasmic reticulum of myotubes. In HeLa cells, tsGFP targeted to
      mitochondria reveals heterogeneity in thermogenesis that correlates with the
      electrochemical gradient. Thus, tsGFPs are powerful tools to noninvasively assess
      thermogenesis in living cells. 

PMID- 24122040
TI  - Detergent-free mass spectrometry of membrane protein complexes.
AB  - We developed a method that allows release of intact membrane protein complexes
      from amphipols, bicelles and nanodiscs in the gas phase for observation by mass
      spectrometry (MS). Current methods involve release of membrane protein complexes
      from detergent micelles, which reveals subunit composition and lipid binding. We
      demonstrated that oligomeric complexes or proteins requiring defined lipid
      environments are stabilized to a greater extent in the absence of detergent. 

PMID- 24122042
TI  - The beta-subunit of cholera toxin has a high affinity for ganglioside GM1
      embedded into solid supported lipid membranes with a lipid raft-like composition.
AB  - In this communication, we report on the fabrication of GM1-rich solid-supported
      bilayer lipid membranes (ssBLM) made of sphingomyelin and cholesterol, the main
      components of lipid rafts,which are the physiological hosting microenvironment of
      GM1 on the cell membrane. The functionality of the ganglioside has been checked
      by measuring the apparent dissociation constant K(D) of the complex formed by the
      beta-subunit of the cholera toxin and GM1. The value found deviates less than one
      order of magnitude from that measured for in vivo cells, indicating the potential
      of these ssBLM as optimized in vitro biomimetic platforms.

PMID- 24122041
TI  - DGIdb: mining the druggable genome.
AB  - The Drug-Gene Interaction database (DGIdb) mines existing resources that generate
      hypotheses about how mutated genes might be targeted therapeutically or
      prioritized for drug development. It provides an interface for searching lists of
      genes against a compendium of drug-gene interactions and potentially 'druggable'
      genes. DGIdb can be accessed at http://dgidb.org/. 

PMID- 24122043
TI  - Spatial recruitment bias in respondent-driven sampling: Implications for HIV
      prevalence estimation in urban heterosexuals.
AB  - Respondent-driven sampling (RDS) is a study design used to investigate
      populations for which a probabilistic sampling frame cannot be efficiently
      generated. Biases in parameter estimates may result from systematic non-random
      recruitment within social networks by geography. We investigate the spatial
      distribution of RDS recruits relative to an inferred social network among
      heterosexual adults in New York City in 2010. Mean distances between recruitment
      dyads are compared to those of network dyads to quantify bias. Spatial regression
      models are then used to assess the impact of spatial structure on risk and
      prevalence outcomes. In our primary distance metric, network dyads were an
      average of 1.34 (95 % CI 0.82-1.86) miles farther dispersed than recruitment
      dyads, suggesting spatial bias. However, there was no evidence that demographic
      associations with HIV risk or prevalence were spatially confounded. Therefore,
      while the spatial structure of recruitment may be biased in heterogeneous urban
      settings, the impact of this bias on estimates of outcome measures appears
      minimal.

PMID- 24122045
TI  - Unipolar hemiarthroplasty versus bipolar hemiarthroplasty in patients with
      displaced femoral neck fractures: a four-year follow-up of a randomised
      controlled trial.
AB  - PURPOSE: The treatment of choice for a displaced femoral neck fracture in the
      most elderly patients is a cemented hemiarthroplasty (HA). The optimal design,
      unipolar or bipolar head, remains unclear. The possible advantages of a bipolar
      HA are a better range of motion and less acetabular wear. The aim of this study
      was to evaluate hip function, health related quality of life (HRQoL), surgical
      outcome and acetabular erosion in a medium-term follow-up. METHODS: One hundred
      and twenty patients aged 80 or more with a displaced fracture of the femoral neck
      (Garden III and IV) were randomised to treatment with a cemented Exeter HA using
      a unipolar or a bipolar head. All patients were able to walk independently, with
      or without aids, before surgery. Follow-ups were performed at four, 12, 24 and 48
      months postoperatively. Assessments included HRQoL (EQ-5D index score), hip
      function (Harris hip score [HHS]) and radiological acetabular erosion. RESULTS:
      The mean EQ-5D index score was generally higher among the patients with bipolar
      hemiarthroplasties at the follow-ups with a significant difference at 48 months:
      unipolar HAs 0.59 and bipolar HAs 0.70 (p = 0.04). There was an increased rate of
      acetabular erosion among the patients with unipolar hemiarthroplasties at the
      early follow-ups with a significant difference at 12 months (unipolar HAs 20% and
      bipolar HAs 5%, p = 0.03). At the later follow-ups the incidence of acetabular
      erosion accelerated in the bipolar group, and there were no significant
      differences between the groups at the 24- and 48-month follow-ups. There was no
      difference in HHS or reoperation rate between the groups at any of the follow
      ups. CONCLUSION: The bipolar HAs seem to result in better HRQoL beyond the first
      two years after surgery compared to unipolar HAs. Bipolar HAs displayed a later
      onset of acetabular erosion compared to unipolar HAs.

PMID- 24122046
TI  - Leonardo Zamudio Villanueva.

PMID- 24122044
TI  - Cost-effectiveness of a package of interventions for expedited antiretroviral
      therapy initiation during pregnancy in Cape Town, South Africa.
AB  - Initiating antiretroviral therapy (ART) early in pregnancy is an important
      component of effective interventions to prevent the mother-to-child transmission
      of HIV (PMTCT). The rapid initiation of ART in pregnancy(RAP) program was a
      package of interventions to expedite ART initiation in pregnant women in Cape
      Town, South Africa. Retrospective cost-effectiveness, sensitivity and threshold
      analyses were conducted of the RAP program to determine the cost-utility
      thresholds for rapid initiation of ART in pregnancy. Costs were drawn from a
      detailed micro-costing of the program. The overall programmatic cost was US$880
      per woman and the base case cost-effectiveness ratio was US$1,160 per quality
      adjusted lifeyear (QALY) saved. In threshold analyses, the RAP program remained
      cost-effective if mother-to-child transmission was reduced by C0.33 %; if C1.76
      QALY were saved with each averted perinatal infection; or if RAP-related costs
      were under US$4,020 per woman. The package of rapid initiation services was very
      cost-effective, as compared to standard services in this setting. Threshold
      analyses demonstrated that the intervention required minimal reductions in
      perinatal infections in order to be cost-effective. Interventions for the rapid
      initiation of ART in pregnancy hold considerable potential as a cost-effective
      use of limited resources for PMTCT in sub-Saharan Africa.

PMID- 24122047
TI  - Surgical fixation of sternal fractures: locked plate fixation by low-profile
      titanium plates--surgical safety through depth limited drilling.
AB  - PURPOSE: Operative treatment of sternal fractures has become a matter of
      increasing interest. Anterior plating seems to be the most appropriate method for
      fixing sternal fractures. However, there are several concerns in relation to the
      operative procedure such as severe injuries to mediastinal organs, patient
      comfort and proper stabilisation, for example. This paper describes a safe method
      of anterior sternal plating using locked plate fixation with limited depth
      drilling. METHODS: Ten patients with sternal fractures were included in this
      cohort study and were treated by anterior plating using one or two plates in
      parallel through a median approach to the sternum. Follow up was performed after
      six weeks, 12 weeks and six months. RESULTS: Follow up revealed no serious
      complications. One patient suffered from postoperative wound seroma. No problems
      were caused by the plates. CONCLUSIONS: Sternal plating using low profile locked
      titanium plates seems to be a safe and stable method with a high level of patient
      comfort.

PMID- 24122048
TI  - Metal-on-metal hip prostheses: correlation between debris in the synovial fluid
      and levels of cobalt and chromium ions in the bloodstream.
AB  - PURPOSE: Hip prostheses with metal-on-metal (MoM) coupling can release cobalt
      chromium particles and ions. The aim of this work is to verify the correlation
      between particles in the synovial fluid and circulating ions. METHODS: Forty
      patients were enrolled; particles from synovial fluid were analysed by SEM-EDX
      (Scanning Electron Microscopy-Energy Dispersion X-rays analysis) and levels of
      circulating Co and Cr were assayed by ICP-MS (inductively-coupled plasma mass
      spectrometry). RESULTS: In 16 cases we did not find any particles in the synovial
      fluid and the Co level in whole blood was 0.05-4.42 ppb; in seven with few
      particles the blood level was 2.2-15.6 ppb; in six cases with several particles
      the level was 5.0-54.3 ppb; finally, in 11 cases we isolated not only Co-Cr
      particles, but also Cr particles with low or absent Co and in these patients the
      circulating level of Co was 23.8-109.6 ppb. Co in serumand Cr level both whole
      blood and serum have shown a similar trend to Co; the correlation between all
      these values and the corresponding particles is statistically significant in all
      cases. CONCLUSION: Co and Cr both in serum and whole blood represents a systemic
      representation of the particle release at local level and can therefore be used
      to confirm a diagnosis and monitor the wear process of MoM articular prostheses.

PMID- 24122049
TI  - Reactive oxygen species-mediated mitochondrial dysfunction plays a critical role
      in high glucose-induced nucleus pulposus cell injury.

PMID- 24122050
TI  - An "off-the-shelf" capillary microfluidic device that enables tuning of the
      droplet breakup regime at constant flow rates.
AB  - The fabrication of glass capillary microfluidic devices is technically
      challenging, often hampering use of the design. We describe a new technique,
      based on commercially available components, for assembling flow focusing
      capillary devices that can readily be taken apart and cleaned between uses. This
      design strategy allows for generation of both water-in-oil and oil-in-water
      emulsions in the same device after an ethanol rinse. The modularity of the device
      enables the adjustment of the tip separation between the two inner capillaries
      during droplet generation, which enables tuning of the age of the interface. Time
      dependent surfactant diffusion to the interface changes the interfacial tension,
      thus providing an approach for adjusting the capillary number in addition to the
      usual method of changing flow rates. This design enables the tuning of the mode
      of breakup and the droplet size. 

PMID- 24122051
TI  - Successful laparoscopic Nissen fundoplication in a patient with mixed connective
      tissue disease with a short esophagus: report of a case.
AB  - A 51-year-old female with esophageal stricture was referred to our hospital. She
      was diagnosed to have mixed connective tissue disease and had been placed on
      steroid and immunosuppressant treatment. She presented with passage disturbance
      and free reflux of the gastric contents when in the supine position. Pneumatic
      dilatation and medication resulted in partial relief of her symptoms.
      Preoperative imaging studies demonstrated a shortened esophagus with severe
      stricture of the esophagogastric junction and a moderate hiatal hernia. A
      DeMeester's score of 140.1 was noted on 24-h pH monitoring. Under a diagnosis of
      stricturing reflux esophagitis, surgical treatment was indicated. Laparoscopic
      transhiatal mediastinal dissection with crural repair and fundoplication was
      offered instead of thoracotomy and/or laparotomy, since she had a high risk due
      to immunosuppression. The esophagus was extensively dissected through the hiatus
      up to the level of the tracheal bifurcation, and fundoplication was completed
      without Collis gastroplasty. Her postoperative course was rapid and uneventful.
      Postoperatively, her clinical symptoms were resolved with anatomical/functional
      improvement.

PMID- 24122052
TI  - Linkage relationships among multiple QTL for horticultural traits and late blight
      (P. infestans) resistance on chromosome 5 introgressed from wild tomato Solanum
      habrochaites.
AB  - When the allele of a wild species at a quantitative trait locus (QTL) conferring
      a desirable trait is introduced into cultivated species, undesirable effects on
      other traits may occur. These negative phenotypic effects may result from the
      presence of wild alleles at other closely linked loci that are transferred along
      with the desired QTL allele (i.e., linkage drag) and/or from pleiotropic effects
      of the desired allele. Previously, a QTL for resistance to Phytophthora infestans
      on chromosome 5 of Solanum habrochaites was mapped and introgressed into
      cultivated tomato (S. lycopersicum). Near-isogenic lines (NILs) were generated
      and used for fine-mapping of this resistance QTL, which revealed coincident or
      linked QTL with undesirable effects on yield, maturity, fruit size, and plant
      architecture traits. Subsequent higher-resolution mapping with chromosome 5 sub
      NILs revealed the presence of multiple P. infestans resistance QTL within this
      12.3 cM region. In our present study, these sub-NILs were also evaluated for 17
      horticultural traits, including yield, maturity, fruit size and shape, fruit
      quality, and plant architecture traits in replicated field experiments over the
      course of two years. Each previously detected single horticultural trait QTL
      fractionated into two or more QTL. A total of 41 QTL were detected across all
      traits, with ~30% exhibiting significant QTL * environment interactions.
      Colocation of QTL for multiple traits suggests either pleiotropy or tightly
      linked genes control these traits. The complex genetic architecture of
      horticultural and P. infestans resistance trait QTL within this S. habrochaites
      region of chromosome 5 presents challenges and opportunities for breeding efforts
      in cultivated tomato. 

PMID- 24122053
TI  - MAPfastR: quantitative trait loci mapping in outbred line crosses.
AB  - MAPfastR is a software package developed to analyze quantitative trait loci data
      from inbred and outbred line-crosses. The package includes a number of modules
      for fast and accurate quantitative trait loci analyses. It has been developed in
      the R language for fast and comprehensive analyses of large datasets. MAPfastR is
      freely available at: http://www.computationalgenetics.se/?page_id=7. 

PMID- 24122054
TI  - Coupling between noise and plasticity in E. coli.
AB  - Expression levels of genes vary not only between different environmental
      conditions ("plasticity") but also between genetically identical cells in
      constant environment ("noise"). Intriguingly, these two measures of gene
      expression variability correlate positively with each other in yeast. This
      coupling was found to be particularly strong for genes with specific promoter
      architecture (TATA box and high nucleosome occupancy) but weak for genes in which
      high noise may be detrimental (e.g., essential genes), suggesting that noise
      plasticity coupling is an evolvable trait in yeast and may constrain evolution of
      gene expression and promoter usage. Recently, similar genome-wide data on noise
      and plasticity have become available for Escherichia coli, providing the
      opportunity to study noise-plasticity correlation and its mechanism in a
      prokaryote, which follows a fundamentally different mode of transcription
      regulation than a eukaryote such as yeast. Using these data, I found significant
      positive correlation between noise and plasticity in E. coli. Furthermore, this
      coupling was highly influenced by the following: level of expression;
      essentiality and dosage sensitivity of genes; regulation by specific nucleoid
      associated proteins, transcription factors, and sigma factors; and involvement in
      stress response. Many of these features are analogous to those found to influence
      noise-plasticity coupling in yeast. These results not only show the generality of
      noise-plasticity coupling across phylogenetically distant organisms but also
      suggest that its mechanism may be similar. 

PMID- 24122055
TI  - Genomic sequence diversity and population structure of Saccharomyces cerevisiae
      assessed by RAD-seq.
AB  - The budding yeast Saccharomyces cerevisiae is important for human food production
      and as a model organism for biological research. The genetic diversity contained
      in the global population of yeast strains represents a valuable resource for a
      number of fields, including genetics, bioengineering, and studies of evolution
      and population structure. Here, we apply a multiplexed, reduced genome sequencing
      strategy (restriction site-associated sequencing or RAD-seq) to genotype a large
      collection of S. cerevisiae strains isolated from a wide range of geographical
      locations and environmental niches. The method permits the sequencing of the same
      1% of all genomes, producing a multiple sequence alignment of 116,880 bases
      across 262 strains. We find diversity among these strains is principally
      organized by geography, with European, North American, Asian, and African/S. E.
      Asian populations defining the major axes of genetic variation. At a finer scale,
      small groups of strains from cacao, olives, and sake are defined by unique
      variants not present in other strains. One population, containing strains from a
      variety of fermentations, exhibits high levels of heterozygosity and a mixture of
      alleles from European and Asian populations, indicating an admixed origin for
      this group. We propose a model of geographic differentiation followed by human
      associated admixture, primarily between European and Asian populations and more
      recently between European and North American populations. The large collection of
      genotyped yeast strains characterized here will provide a useful resource for the
      broad community of yeast researchers. 

PMID- 24122056
TI  - Rapid degeneration of noncoding DNA regions surrounding SlAP3X/Y after
      recombination suppression in the dioecious plant Silene latifolia.
AB  - Silene latifolia is a dioecious plant with heteromorphic XY sex chromosomes.
      Previous studies of sex chromosome-linked genes have suggested a gradual
      divergence between the X-linked and the Y-linked genes in proportion to the
      distance from the pseudoautosomal region. However, such a comparison has yet to
      be made for the noncoding regions. To better characterize the nonrecombining
      region of the X and Y chromosomes, we sequenced bacterial artificial chromosome
      clones containing the sex chromosome-linked paralogs SlAP3X and SlAP3Y, including
      115 kb and 73 kb of sequences, respectively, flanking these genes. The synonymous
      nucleotide divergence between SlAP3X and SlAP3Y indicated that recombination
      stopped approximately 3.4 million years ago. Sequence homology analysis revealed
      the presence of six long terminal repeat retrotransposon-like elements. Using the
      nucleotide divergence calculated between left and right long terminal repeat
      sequences, insertion dates were estimated to be 0.083-1.6 million years ago,
      implying that all elements detected were inserted after recombination stopped. A
      reciprocal sequence homology search facilitated the identification of four
      homologous noncoding DNA regions between the X and Y chromosomes, spanning 6.7%
      and 10.6% of the X chromosome-derived and Y chromosome-derived sequences,
      respectively, investigated. Genomic Southern blotting and fluorescence in situ
      hybridization showed that the noncoding DNA flanking SlAP3X/Y has homology to
      many regions throughout the genome, regardless of whether they were homologous
      between the X and Y chromosomes. This finding suggests that most noncoding DNA
      regions rapidly lose their counterparts because of the introduction of
      transposable elements and indels (insertion-deletions) after recombination has
      stopped. 

PMID- 24122057
TI  - RNA-guided genome editing for target gene mutations in wheat.
AB  - The clustered, regularly interspaced, short palindromic repeats (CRISPR) and
      CRISPR-associated protein (Cas) system has been used as an efficient tool for
      genome editing. We report the application of CRISPR-Cas-mediated genome editing
      to wheat (Triticum aestivum), the most important food crop plant with a very
      large and complex genome. The mutations were targeted in the inositol oxygenase
      (inox) and phytoene desaturase (pds) genes using cell suspension culture of wheat
      and in the pds gene in leaves of Nicotiana benthamiana. The expression of
      chimeric guide RNAs (cgRNA) targeting single and multiple sites resulted in indel
      mutations in all the tested samples. The expression of Cas9 or sgRNA alone did
      not cause any mutation. The expression of duplex cgRNA with Cas9 targeting two
      sites in the same gene resulted in deletion of DNA fragment between the targeted
      sequences. Multiplexing the cgRNA could target two genes at one time. Target
      specificity analysis of cgRNA showed that mismatches at the 3' end of the target
      site abolished the cleavage activity completely. The mismatches at the 5' end
      reduced cleavage, suggesting that the off target effects can be abolished in vivo
      by selecting target sites with unique sequences at 3' end. This approach provides
      a powerful method for genome engineering in plants. 

PMID- 24122058
TI  - Investigation of Alteration in the Levels of Iron and Copper in Scalp Hair
      Samples of Patients Having Different Types of Viral Hepatitis.
AB  - The aim of this study was to measure the alterations of copper and iron contents
      in scalp hair samples of hepatitis A-E patients of both genders, same age group,
      and socioeconomic status. For comparative study, the scalp hair samples of
      healthy individuals of the same age and socioeconomic status were collected. The
      concentrations of copper and iron were measured using an atomic absorption
      spectrophotometer, after microwave-assisted acid digestion. The validity and
      accuracy of methodology was checked using a certified reference material. The
      results of this study showed that the mean values of copper and iron were higher
      in scalp hair samples of hepatitis patients than those of age-matched control
      subjects, while the difference was significant in the cases of patients having
      viral hepatitis B, C, and D as compared to those who have viral hepatitis A and E
      (p < 0.001). It was concluded that the overload of copper and iron in the human
      body may cause lipid peroxidation and eventually damage the hepatic system.

PMID- 24122059
TI  - Marked phenotypic variability in two siblings with congenital myasthenic syndrome
      due to mutations in MUSK.

PMID- 24122060
TI  - Levels of HVA, 5-HIAA, and MHPG in the CSF of vascular parkinsonism compared to
      Parkinson's disease and controls.
AB  - The neurochemical abnormalities underlying vascular parkinsonism (VP) have not
      been well characterised. A better understanding may help to optimize
      pharmacological interventions. Since VP patients generally have a poorer response
      to l-Dopa than Parkinson's disease (PD) patients, we investigated whether levels
      of relevant CSF neurotransmitter metabolites may be differentially altered in VP
      and PD and assessed the potential of neurotransmitter metabolites as biomarkers.
      We compared CSF levels of homovanillic acid (HVA), 5-hydroxyindolacetic acid, and
      3-methoxy-4-hydroxyphenylethyleneglycol, in 16 VP patients, 57 PD patients and 60
      non-neurological controls. We found that levels of HVA were reduced in PD
      compared with both VP and controls but did not differ significantly between VP
      and controls indicating that dopamine deficiency was less pronounced in VP.

PMID- 24122061
TI  - Serum anticardiolipin antibodies in patients with neuromyelitis optica spectrum
      disorder.
AB  - The presence of anticardiolipin antibodies (ACLA) in multiple sclerosis (MS)
      patients has been reported, but there are some debates on the relationship
      between ACLA and MS. We assessed the clinical features of neuromyelitis optica
      spectrum disorders (NMOSD) patients with ACLA. A consecutive cohort of 480
      subjects with NMOSD (n = 70), MS (n = 90) and control (n = 220) were analysed
      retrospectively. Patients' serum was tested by a dot-immunogold filtration assay
      for the presence of ACLA-IgG, IgM and IgA antibodies. In MS patients, 5 (5.6 %)
      of the 90 patients showed ACLA-IgG reactivity in the serum. In NMOSD patients, 32
      (45.7 %) of the 70 patients showed ACLA reactivity in the serum, among which ACLA
      IgG seropositivity was 45.7 % (32/70), ACLA-IgG + IgM seropositivity was 8.6 %
      (6/70), and ACLA-IgG + IgA seropositivity was 4.3 % (3/70). NMOSD patients were
      higher in ACLA-IgG (p < 0.0001) and ACLA-IgG + IgM (p = 0.006) than the MS
      patients. NMOSD patients had higher ACLA-IgG than the control patients (p <
      0.0001). In comparison with the controls, the MS patients were lower in ACLA for
      IgG (p = 0.014) and IgM (p = 0.004). Seropositive ACLA patients increased in age
      (p = 0.013) and had higher D-dimer levels (DD) (p = 0.002) than the seronegative
      NMOSD patients. Furthermore, positive ACLA-IgG + IgM patients were increased in
      age (p = 0.001), had higher baseline EDSS (p = 0.001), antithrombin III activity
      (p = 0.04), and DD levels (p = 0.005) than the pure positive ACLA-IgG NMOSD
      patients. Patients with NMOSD had more occurrences of ACLA than patients with MS.
      NMOSD patients with positive ACLA-IgG + IgM had a worse outcome that may be
      associated with elder age and abnormal coagulation parameters in blood.

PMID- 24122062
TI  - Variations of mitochondrial DNA polymerase gamma in patients with Parkinson's
      disease.
AB  - Parkinson's disease is associated with mitochondrial dysfunction. The POLG1 gene
      encodes DNA-polymerase gamma, which is responsible for the replication of
      mitochondrial DNA. Mutations in POLG1 cause neurodegenerative diseases such as
      progressive external ophthalmoplegia and Alpers syndrome. In this study, we
      investigated if mutations in POLG1 had any correlation with Parkinson's disease.
      Subjects consisted of Finnish patients with early-onset Parkinson's disease
      (EOPD, N = 441) or late-onset Parkinson's disease (LOPD, N = 263). The POLG1 gene
      was screened for nine previously known mutations. Two patients were compound
      heterozygotes with respect to putatively pathogenic alleles. Twenty-eight
      patients harbored a heterozygous missense mutation, but the allele frequencies
      did not differ from those of the controls. Interestingly, the frequency of
      affected siblings was 4.6-fold higher (95 % confidence interval; 1.09, 19.5)
      among the patients with EOPD and with heterozygous POLG1 mutations than among
      patients without mutations. Clinically the patients with or without POLG1
      mutations did not differ from each other. Our findings provide two lines of
      evidence suggesting a role for POLG1 mutations in Parkinson's disease: (1)
      identification of patients with compound heterozygous mutations in POLG1, and (2)
      higher frequency of affected siblings among the EOPD patients with heterozygous
      POLG1 mutations than among EOPD patients without mutations.

PMID- 24122063
TI  - Usefulness of intravenous lacosamide in status epilepticus.
AB  - Lacosamide (LCM) is a treatment option for status epilepticus (SE) described in
      several series. We therefore proposed to describe its use in status epilepticus
      patients in our hospital. All patients admitted to our hospital for SE from
      September 2010 to April 2012 were evaluated. We collected related variables
      including the type of SE, etiology, antiepileptic drugs (AEDs) used, loading dose
      of AEDs, cessation of SE after AEDs, ICU admission and mortality. In those
      patients receiving LCM, we reviewed the infusion rate and time to response. We
      compared patients receiving LCM with patients in whom it was not used. This was a
      retrospective and uncontrolled study. A total of 92 patients were included; 67.7
      % of SE patients who received LCM responded to treatment. The vast majority of
      the patients presented non-convulsive and motor focal SE. When we selected
      patients to receive four or more AEDs, the LCM efficacy was 55.6 %, a very
      similar result compared to when it was not used. Subsequently, we analyzed the
      sample regarding the AED administered as the second or third line of treatment,
      and the responder rate was significantly higher when LCM was used (84.6 vs. 47.8
      %, p 0.041). After an adjusted regression analysis, the use of LCM was
      independently associated with cessation of SE. The total percentage of
      undesirable effects was very low (12 %), and they were all mild. No relationship
      was found between a specific etiology and better response. LCM is a useful drug
      that represents an alternative in the treatment of non-convulsive or focal motor
      SE. Its efficacy might be more important when it is administered as a second or
      third option after benzodiazepines. A randomized trial is required to confirm
      these results.

PMID- 24122064
TI  - Longitudinal study of cognitive and psychiatric functions in spinocerebellar
      ataxia types 1 and 2.
AB  - The role of the cerebellum in cognition, both in healthy subjects and in patients
      with cerebellar diseases, is debated. Neuropsychological studies in
      spinocerebellar ataxia type 1 (SCA1) and type 2 (SCA2) demonstrated impairments
      in executive functions, verbal memory, and visuospatial performances, but
      prospective evaluations are not available. Our aims were to assess progression of
      cognitive and psychiatric functions in patients with SCA1 and SCA2 in a
      longitudinal study. We evaluated at baseline 20 patients with SCA1, 22 patients
      with SCA2 and 17 matched controls. Two subgroups of patients (9 SCA1, 11 SCA2)
      were re-evaluated after 2 years. We tested cognitive functions (Mini Mental State
      Examination, digit span, Corsi span, verbal memory, attentional matrices,
      modified Wisconsin Card Sorting Test, Raven Progressive Matrices, Benton test,
      phonemic and semantic fluency), psychiatric status (Scales for Assessment of
      Negative and Positive Symptoms, Hamilton Depression and Anxiety Scales),
      neurological conditions (Scale for Assessment and Rating of Ataxia), and
      functional abilities (Unified Huntington Disease Rating Scale-part IV). At
      baseline, SCA1 and SCA2 patients had significant deficits compared to controls,
      mainly in executive functions (phonemic and semantic fluencies, attentional
      matrices); SCA2 showed further impairment in visuospatial and visuoperceptive
      tests (Raven matrices, Benton test, Corsi span). Both SCA groups had higher
      depression and negative symptoms, particularly apathy, compared to controls.
      After 2 years, motor and functional disability worsened, while only attentive
      performances deteriorated in SCA2. This longitudinal study showed dissociation in
      progression of motor disability and cognitive impairment, suggesting that in SCA1
      and SCA2 motor and cognitive functions might be involved with different
      progression rates.

PMID- 24122066
TI  - One-pot synthesis of Fe2O3 yolk-shell particles with two, three, and four shells
      for application as an anode material in lithium-ion batteries.
AB  - Fe2O3 yolk-shell particles with two, three, and four shells are prepared by one
      pot spray pyrolysis. The discharge capacity of the Fe2O3 yolk-shell particles
      with two shells showing the best electrochemical properties is as high as 848 mA
      h g(-1) after 80 cycles at a current density of 300 mA g(-1). 

PMID- 24122065
TI  - A literature review and novel theoretical approach on the optical properties of
      whole blood.
AB  - Optical property measurements on blood are influenced by a large variety of
      factors of both physical and methodological origin. The aim of this review is to
      list these factors of influence and to provide the reader with optical property
      spectra (250-2,500 nm) for whole blood that can be used in the practice of
      biomedical optics (tabulated in the appendix). Hereto, we perform a critical
      examination and selection of the available optical property spectra of blood in
      literature, from which we compile average spectra for the absorption coefficient
      (MU(a)), scattering coefficient (MU(s)) and scattering anisotropy (g). From this,
      we calculate the reduced scattering coefficient (MU(s)') and the effective
      attenuation coefficient (MU(eff)). In the compilation of MU(a) and MU(s), we
      incorporate the influences of absorption flattening and dependent scattering
      (i.e. spatial correlations between positions of red blood cells), respectively.
      For the influence of dependent scattering on MU(s), we present a novel,
      theoretically derived formula that can be used for practical rescaling of MU(s)
      to other haematocrits. Since the measurement of the scattering properties of
      blood has been proven to be challenging, we apply an alternative, theoretical
      approach to calculate spectra for MU(s) and g. Hereto, we combine Kramers-Kronig
      analysis with analytical scattering theory, extended with Percus-Yevick structure
      factors that take into account the effect of dependent scattering in whole blood.
      We argue that our calculated spectra may provide a better estimation for MU(s)
      and g (and hence MU(s)' and MU(eff)) than the compiled spectra from literature
      for wavelengths between 300 and 600 nm.

PMID- 24122067
TI  - Analysis of complete genomes of isolates of the Wheat dwarf virus from new
      geographical locations and descriptions of their defective forms.
AB  - Recently, the importance of the Geminiviruses infecting cereal crops has been
      appreciated, and they are now being studied in detail. Barley and wheat strains
      of Wheat dwarf virus are recorded in most European countries. Information on
      complete sequences of isolates from the United Kingdom, Spain, and Austria are
      reported here for the first time. Analysis revealed that their sequences are very
      stable. Recombination between strains was recorded only for the barley strain. We
      identified several defective forms of the barley strain from barley and wheat,
      which do not influence symptom expression. Sequences of barley isolates infecting
      wheat were obtained that did not differ from the isolates from barley. Based on
      specific features of the SIR of the barley strains, it is suggested that they are
      assigned to one of the two proposed new clusters, A1 or A2.

PMID- 24122068
TI  - The C2 protein of Bhendi yellow vein mosaic virus plays an important role in
      symptom determination and virus replication.
AB  - Bhendi yellow vein mosaic virus (BYVMV) that causes bhendi yellow vein mosaic
      disease is a monopartite begomovirus with an associated betasatellite. Previous
      studies have shown that C2 protein of BYVMV acts as a suppressor of post
      transcriptional gene silencing, activates transcription, localizes to nucleus,
      and interacts with karyopherin alpha. To probe the role of C2 in symptom
      determination and virus replication, the infectious clones of BYVMV containing
      two stop codons in the C2 ORF were created and used for infection studies. The
      Nicotiana benthamiana plants infiltrated with the infectious clones harboring
      stop codons in the C2 ORF did not develop any symptoms unlike plants infiltrated
      with wild-type BYVMV. Southern blotting and real time PCR analysis revealed that
      the viral load was reduced drastically in the plants infected with BYVMV
      containing the nontranslatable version of C2 ORF. However, there was a recovery
      in viral DNA replication, when co-infiltrated with wild-type betasatellite. Hence
      we conclude that the C2 protein of BYVMV plays an important role in symptom
      determination and viral DNA replication.

PMID- 24122069
TI  - Evaluation of Photographic Variables in Patients with Indication for Facial
      Rejuvenation.
AB  - BACKGROUND: Photography standardization is paramount for appropriate critical
      analysis of aesthetic surgery outcomes. Therefore, the authors designed a study
      to evaluate the influence of different variables in photos of patients with
      indications for undergoing facial rejuvenation. METHODS: This blinded prospective
      study was conducted by the Section of Plastic Surgery in the Hospital das
      Clinicas at the Federal University of Parana. In the study, 29 patients had their
      photos taken in two separate settings. Photo 1, termed "preoperative" (Pre), was
      obtained according to the same pattern for all patients. Photo 2, termed
      "postoperative" (Post), was acquired on the same day using different variables to
      manipulate the photo outcome. No surgery was actually performed. Both photos (Pre
      and Post) were sent to five experienced Brazilian plastic surgeons, who provided
      a score for photo 2 that varied from -10 to +10 compared with photo 1. RESULTS:
      The photos were examined by 119 plastic surgeons. No significant improvement was
      observed in most of the groups, except for the group that used a flash for the
      Post photography (p = 0.035). Almost half of the scores (45.37 %) were above
      zero. The highest score was found to be ten for two photographs of the makeup
      group. A score of zero was assigned to 54.62 % of the photos, which means no
      changes occurred between the Pre and Post photos. CONCLUSION: Inadequate
      photographic technique can change assessments of photos in a meaningful way. All
      the factors evaluated had a positive impact, but the only statistically
      significant variable was the use of a flash in the Post group. LEVEL OF EVIDENCE
      II: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24122070
TI  - Comparison of the Rubin dermal suspension sutures and total parenchymal reshaping
      technique with a traditional inverted T-scar reduction mammaplasty technique
      using a superior pedicle.
AB  - Adipose patients, especially after massive weight loss, pose a challenge to the
      breast surgeon due to the major loss of volume and the inelasticity of the skin.
      Rubin described a suitable mammaplasty technique for these patients involving
      dermal suspension sutures and total parenchymal reshaping. With this technique,
      the tissue of the prominent axillary skin fold typically found in patients with
      massive weight loss is used to increase the upper pole volume of the breast. To
      prove the effectiveness of this technique, the current study compared it with a
      traditional inverted T-scar technique using a superior pedicle, as described by
      Hohler. This technique usually is used for a different patient clientele that
      requires reduction mammaplasty. However, because none of the difficult
      aforementioned preconditions are found in this clientele, it leads to the best
      possible outcome and represents the authors' internal "gold standard" for
      mammaplasty against which all other techniques must be compared. This study
      retrospectively analyzed the complication rate, lift effect, and upper pole
      fullness by chart analysis and photometric analysis of 21 Hohler and 24 Rubin
      mammaplasties. Despite the more challenging patient clientele in the Rubin
      groups, both therapies achieved a similar lift effect without significant
      differences (Hohler 4.8 +/- 3.3 cm vs Rubin 6 +/- 4 cm). In both groups, the
      upper pole area increased significantly. The ratio of upper pole-to-lower pole
      area increased from 1.31 preoperatively to 2.1 postoperatively in the Rubin
      group, suggesting a redistribution of tissue in favor of the upper pole, and it
      increased from 1.18 to 1.69 in the Hohler group, indicating an even greater
      increase in upper pole volume in the Rubin group. In conclusion, the technique
      described by Rubin, despite the dramatically more difficult soft tissue condition
      of the patients with massive weight loss, results in an outcome similar to that
      of a traditional reduction mammaplasty technique in terms of increased upper pole
      volume. It is suitable and preferable for patients who have a lateral axillary
      roll deformity and can be applied safely for these patients without increasing
      the complication rate. LEVEL OF EVIDENCE IV: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266.

PMID- 24122071
TI  - A comparison of skin expansion and contraction between one expander and two
      expanders: a preliminary study.
AB  - BACKGROUND: This study aimed to compare the difference between the skin expansion
      and contraction rates for an expanded flap with one versus two expanders.
      METHODS: The study cohort comprised 24 cases of two overlapping expanders and 15
      cases of a single implanted expander involving 22 patients. The method of "wet
      cloth sampling" was applied to measure the expanded flap area and the initial
      unexpanded area and to calculate the skin expansion rate. Two points 5 cm apart
      in the center of the expanded flap were selected before the second surgical
      stage. After removal of the expander, the distance between the two fixed points
      was measured and recorded. The contraction rate of the expanded flap then was
      calculated. RESULTS: During the same period of expansion in the two groups (p =
      0.06, >0.01), the skin expansion rate was 3.5 +/- 0.9 % in the group with two
      overlapping expanders and 2.6 +/- 0.6 % in the control group. The difference
      between the two groups was statistically significant (p = 0.002, <0.05). The
      instantly expanded flap contraction rates were 30.3 +/- 0.8 and 32.3 +/- 0.9 %,
      respectively for the two groups, and the difference was not statistically
      significant (p = 0.47, >0.05). We fitted a linear regression model that was Y =
      0.533 - 0.003X, where Y was the contraction rate of the expanded flap and X was
      the period of expansion. The contraction rate of the expanded flap was negatively
      correlated with the period of expansion. CONCLUSIONS: Compared with the
      traditional method of implanting a single expander, the new method of overlapping
      two expanders in a single cavity increased the skin expansion rate. The instantly
      expanded flap contraction rate did not differ significantly between the two
      groups, so the amount of expanded skin area absolutely increased. The clinical
      application of the new method is worth promoting. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266.

PMID- 24122072
TI  - Re: Caiulo VA, Gargani L, Caiulo S, Fisicaro A, Moramarco F, Latini G, Picano E.
      Lung ultrasound in bronchiolitis: comparison with chest X-ray. Eur J Pediatr.
      2011;170: 1427-33.

PMID- 24122073
TI  - Elevated Th17 cells accompanied by decreased regulatory T cells and cytokine
      environment in infants with biliary atresia.
AB  - PURPOSE: The aim of this study was to investigate the role of Th17 and T reg
      cells in biliary atresia (BA) and to assess the liver cytokine environment in BA
      patients. METHODS: The percentages of Th17 and T reg cells in peripheral blood
      mononuclear cells (PBMCs) of BA patients and healthy controls (HC) were
      evaluated. The serum concentrations of IL-17a and IL-23 as well as Foxp3, IL-17a,
      ROR-gammat, IL-6, IL-1beta and TGF-beta1 m-RNA and protein expressions in liver
      tissues and the number of Foxp3, IL-17a, ROR-gammat, CD4 expressing cells which
      infiltrated the hepatic tissues were determined. RESULTS: The Th17/T reg cell
      ratio (P < 0.001) and blood concentrations of IL-17a and IL-23 (P < 0.05) were
      increased in the BA as compared to the HC group. Expressions of Foxp3, ROR
      gammat, IL-17a, IL-1beta, IL-6 as well as TGF-beta1 mRNA and proteins were
      significantly increased in BA as compared to HC livers (P < 0.01, P < 0.05). High
      levels of IL-17a/ROR-gammat-positive and moderate levels of Foxp3-positive cells
      infiltrated damaged BA bile ducts and the ratio of FoxP3+ T to CD4+ T cells was
      significantly lower in BA than in HC samples (P < 0.01). CONCLUSION: Cytokine
      induced imbalance between Th17 and T reg cells in BA livers may be involved in
      bile duct damage.

PMID- 24122074
TI  - Preserving the azygos vein when repairing esophageal atresia and
      tracheoesophageal fistula accompanied by interrupted inferior vena cava.
AB  - This report describes an infant born with esophageal atresia, tracheoesophageal
      fistula, right-sided diaphragmatic hernia, and an interrupted inferior vena cava
      (IVC) that underwent successful repair. The report emphasizes the importance of
      diagnosing an interrupted IVC prior to tracheoesophageal repair.

PMID- 24122076
TI  - Elevated preoperative blood pressure predicts the intraoperative loss of SSEP
      neuromonitoring signals during spinal surgery.
AB  - Intraoperative neuromonitoring of somatosensory evoked potentials (SSEPs) can
      allow identification of evolving neurologic deficit. However, SSEP deterioration
      is not always associated with postoperative deficit. Transient physiologic
      changes, including a decrease in blood pressure (BP), can result in signal
      deterioration, defined as a decrease in waveform amplitude of[50 %seen without
      neurologic deficit. This study examines the relationship between intraoperative
      BP decrease and SSEP neuromonitoring to determine whether hypertensive patients
      are more prone to decreases in BP and if such BP declines are associated with
      signal loss. We conducted a retrospective review of 43 lumbar laminectomy
      patients at Mount Sinai. Patients were categorized based on whether they had a
      previous hypertension diagnosis and if they presented with a first systolic BP of
      greater than 140 mmHg in the admission area on the morning of surgery, two groups
      that were not mutually exclusive. We measured BP drop by calculating fractional
      mean arterial pressure (fMAP, lowest MAP/baseline MAP) and change in BP.We
      identified patients' SSEP tracings in which signal amplitude decreased[50 %.
      After dividing patients' recording times into 5-min epochs, we calculated median
      MAP and whether SSEPs deteriorated in each epoch. We compared the likelihood of
      signal loss in hypertensives to patients presenting with elevated BP, calculating
      the odds ratio. Elevated BP prior to surgery is associated with lower fMAP (p =
      0.007) and a larger intraoperative decrease in BP (p?0.001).A diagnosis of
      hypertension is not associated with lower fMAP orBP drop. Lower epoch fMAPis
      associated with signal loss (p = 0.0026). While the presence of preoperative
      elevated BP predicts SSEP abnormality (p = 0.0039), a diagnosis of hypertension
      does not. Elevated BP, not a hypertension diagnosis, is associated with
      intraoperative loss of SSEP signals. This effect of elevated BP on SSEPs may be
      due to the larger associated intraoperative BP decline.

PMID- 24122075
TI  - Sexual and physical abuse in childhood is associated  with depression and anxiety
      over the life course: systematic review  and meta-analysis.
AB  - OBJECTIVES: To determine whether depression and anxiety in adulthood are
      associated with abuse exposure in childhood. METHODS: A search of PUBMED, EMBASE
      and PSYCHINFO databases (2002-2012) was supplemented by hand searches of
      bibliographies of articles and reviews. We included studies contrasting abuse
      exposure vs. no-abuse exposure before age 16 years to depression and anxiety
      after age 16 years. Data on sample and exposure and outcome instruments,
      covariates and odds ratios (ORs) with the respective 95 % confidence intervals
      (CI) were extracted. Combined ORs and 95 % CI were calculated using random
      effects models. Heterogeneity was quantified using the I(2) test. RESULTS:
      Inclusion criteria were met by 19 studies with 115,579 study participants, for
      assessing depression (n = 14) and anxiety (n = 13). The combined ORs for
      depression were 2.04 (95 % CI: 1.65-2.53) for sexual abuse and 1.49 (95 % CI:
      1.29-1.72) for physical abuse.The combined ORs for anxiety were 2.52 (95 %
      CI:2.12-2.98) for sexual abuse and 1.70 (95 % CI: 1.33-2.18)for physical abuse.
      CONCLUSIONS: High levels of depression, anxiety and distress are reported in
      adults exposed to childhood sexual and physical abuse. These findings require
      increased awareness for the potential needs of adults exposed to child abuse and
      public health interventions to prevent child abuse.

PMID- 24122077
TI  - Entropy correlates with Richmond Agitation Sedation Scale in  mechanically
      ventilated critically ill patients.
AB  - Sedation is routinely used in intensive care units. However due to absence of
      objective scoring systems like Bispectral Index and entropy our ability to
      regulate the degree of sedation is limited. This deficiency is further
      highlighted by the fact that agitation scores used in intensive care units (ICU)
      have no role in paralyzed patients. The present study compares entropy as a
      sedation scoring modality with Richmond Agitation Sedation Scale (RASS) in
      mechanically ventilated, critically ill patients in an ICU. Twenty-seven,
      mechanically ventilated, critically ill patients of either sex, 16-65 years of
      age, were studied over a period of 24 h. They received a standard sedation
      regimen consisting of a bolus dose of propofol 0.5 mg/kg and fentanyl 1 lg/kg
      followed by infusions of propofol and fentanyl ranging from 1.5 to 5 mg/kg/h and
      0.5 to 2.0 lg/kg/h, respectively. Clinically relevant values of RASS for optimal
      ICU sedation (between 0 and -3) in non-paralyzed patients were compared to
      corresponding entropy values, to find if any significant correlation exists
      between the two. These entropy measurements were obtained using the Datex-Ohmeda
      M-EntropyTM module. This module is presently not approved by Food and Drug
      Administration (FDA) for monitoring sedation in ICU. A total of 527 readings were
      obtained. There was a statistically significant correlation between the state
      entropy (SE) and RASS [Spearman's rho/rs = 0.334, p?0.0001]; response entropy
      (RE) and RASS [Spearman's rho/rs = 0.341, p?0.0001]). For adequate sedation as
      judged by a RASS value of 0 to -3, the mean SE was 57.86 +/- 16.50 and RE was
      67.75 +/- 15.65. The present study illustrates that entropy correlates with RASS
      (between scores 0 and -3) when assessing the level of sedation in mechanically
      ventilated critically ill patients.

PMID- 24122078
TI  - Role of the mirror-neuron system in cross-education.
AB  - The present review proposes the untested hypothesis that cross-education
      performed with a mirror increases the transfer of motor function to the resting
      limb compared with standard cross-education interventions without a mirror. The
      hypothesis is based on neuroanatomical evidence suggesting an overlap in
      activated brain areas when a unilateral motor task is performed with and without
      a mirror in the context of cross-education of the upper extremities. The review
      shows that the mirror-neuron system (MNS), connecting sensory neurons responding
      to visual properties of an observed action and motor neurons that discharge
      action potentials during the execution of a similar action, has the potential to
      enhance cross-education.

PMID- 24122079
TI  - GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with
      Benzodiazepines.
AB  - GABAA receptor mediated inhibition plays an important role in modulating the
      input/output dynamics of cerebellum. A characteristic of cerebellar GABAA
      receptors is the presence in cerebellar granule cells of subunits such as alpha6
      and delta which give insensitivity to classical benzodiazepines. In fact,
      cerebellar GABAA receptors have generally been considered a poor model for
      testing drugs which potentially are active at the benzodiazepine site. In this
      overview we show how rat cerebellar granule cells in culture may be a useful
      model for studying new benzodiazepine site agonists. This is based on the
      pharmacological separation of diazepam-sensitive alpha1 beta2/3 gamma2 receptors
      from those which are diazepam-insensitive and contain the alpha6 subunit. This is
      achieved by utilizing furosemide/Zn2+ which block alpha6 containing and
      incomplete receptors.

PMID- 24122080
TI  - Glutamate dehydrogenase: structure, allosteric regulation, and role in insulin
      homeostasis.
AB  - Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the
      reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Only in the
      animal kingdom is this enzyme heavily allosterically regulated by a wide array of
      metabolites. The major activators are ADP and leucine and inhibitors include GTP,
      palmitoyl CoA, and ATP. Spontaneous mutations in the GTP inhibitory site that
      lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to
      why mammalian GDH is so tightly regulated. Patients with HHS exhibit
      hypersecretion of insulin upon consumption of protein and concomitantly extremely
      high levels of ammonium in the serum. The atomic structures of four new
      inhibitors complexed with GDH complexes have identified three different
      allosteric binding sites. Using a transgenic mouse model expressing the human HHS
      form of GDH, at least three of these compounds blocked the dysregulated form of
      GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to
      amino acids in whole animals and improved basal serum glucose levels. The atomic
      structure of the ECG-GDH complex and mutagenesis studies is directing structure
      based drug design using these polyphenols as a base scaffold. In addition, all of
      these allosteric inhibitors are elucidating the atomic mechanisms of allostery in
      this complex enzyme. 

PMID- 24122081
TI  - XQ-1H Suppresses Neutrophils Infiltration and Oxidative Stress Induced by
      Cerebral Ischemia Injury Both In Vivo and In Vitro.
AB  - Cerebral ischemia/reperfusion injury plays an important role in the development
      of tissue injury after acute stroke, including neutrophils adhesion and
      infiltration, inflammation and oxidative stress. 10-O-(N,N-dimethylaminoethyl)
      ginkgolide B methanesulfonate (XQ-1H) is a novel ginkdolide B derivative. In this
      study, we investigated the anti-inflammatory and anti-oxidative activities of XQ
      1H in vivo and vitro. In our study, rats were treating with XQ-1H (31.2, 15.6 and
      7.8 mg/kg) after middle cerebral artery occlusion surgery. Primary cultured
      cortical rat neurons were treated with Na2S2O4 for 1.5 h to mimic hypoxia and
      reoxygenation injury in vitro. Cortical neurons were preincubated with XQ-1H
      (100, 10, 1 MUM) 24 h before hypoxic injury. Brain edema was evaluated by brain
      water content. Neutrophil infiltration was determined by fluorescence imaging
      method and myeloperoxidase assay. Intercellular adhesion molecule 1 (ICAM-1) and
      matrix metallopeptidase 9 (MMP-9) expressions were examined by
      immunohistochemistry analysis. Neuronal injury was assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, lactate dehydrogenase
      releasing and lactic acid content. The anti-oxidative effects of XQ-1H were
      evaluated by superoxide dismutase (SOD) activity and malondialdehyde content in
      ischemic brain and neuron cultures subjected to hypoxia/reoxygenation procedure.
      Results showed that XQ-1H reduced neutrophils infiltration to ischemic brain,
      which might result from down regulation of inflammatory mediators, such as ICAM-1
      and MMP-9. In addition, an antioxidative effect of XQ-1H was observed in cortical
      neuron and brain homogenates by enhancing SOD activity and inhibiting lipid
      peroxidation. These results indicated that XQ-1H possessed a protective effect
      against cerebral ischemia, especially on neutrophil infiltration and oxidative
      stress.

PMID- 24122082
TI  - Electronic and plasmonic phenomena at graphene grain boundaries.
AB  - Graphene, a two-dimensional honeycomb lattice of carbon atoms of great interest
      in (opto)electronics and plasmonics, can be obtained by means of diverse
      fabrication techniques, among which chemical vapour deposition (CVD) is one of
      the most promising for technological applications. The electronic and mechanical
      properties of CVD-grown graphene depend in large part on the characteristics of
      the grain boundaries. However, the physical properties of these grain boundaries
      remain challenging to characterize directly and conveniently. Here we show that
      it is possible to visualize and investigate the grain boundaries in CVD-grown
      graphene using an infrared nano-imaging technique. We harness surface plasmons
      that are reflected and scattered by the graphene grain boundaries, thus causing
      plasmon interference. By recording and analysing the interference patterns, we
      can map grain boundaries for a large-area CVD graphene film and probe the
      electronic properties of individual grain boundaries. Quantitative analysis
      reveals that grain boundaries form electronic barriers that obstruct both
      electrical transport and plasmon propagation. The effective width of these
      barriers (~10-20 nm) depends on the electronic screening and is on the order of
      the Fermi wavelength of graphene. These results uncover a microscopic mechanism
      that is responsible for the low electron mobility observed in CVD-grown graphene,
      and suggest the possibility of using electronic barriers to realize tunable
      plasmon reflectors and phase retarders in future graphene-based plasmonic
      circuits. 

PMID- 24122083
TI  - Formation and electronic properties of InSb nanocrosses.
AB  - Signatures of Majorana fermions have recently been reported from measurements on
      hybrid superconductor-semiconductor nanowire devices. Majorana fermions are
      predicted to obey special quantum statistics, known as non-Abelian statistics. To
      probe this requires an exchange operation, in which two Majorana fermions are
      moved around one another, which requires at least a simple network of nanowires.
      Here, we report on the synthesis and electrical characterization of crosses of
      InSb nanowires. The InSb wires grow horizontally on flexible vertical stems,
      allowing nearby wires to meet and merge. In this way, near-planar single
      crystalline nanocrosses are created, which can be measured by four electrical
      contacts. Our transport measurements show that the favourable properties of the
      InSb nanowire devices-high carrier mobility and the ability to induce
      superconductivity--are preserved in the cross devices. Our nanocrosses thus
      represent a promising system for the exchange of Majorana fermions.

PMID- 24122084
TI  - Surface plasmons: A probe for graphene electronics.

PMID- 24122086
TI  - Brief communication: cranial nonmetric trait database on the internet.
AB  - This brief note announces the publication of a nonmetric cranial trait database
      as a freely available resource on the Internet at:
      http://library.queensu.ca/webdoc/ssdc/cntd. The files were constructed in the
      program Excel, and are available also in comma-delimited format. These one
      observer data on 38 traits were recorded in 1963-2003 in skeletal collections
      curated at many museums. The 8,016 crania represent individuals from a broad
      geographic and temporal range of recent human populations, with regions best
      represented being the Arctic and northwestern North America.

PMID- 24122088
TI  - Economic adversity and depressive symptoms in mothers: Do marital status and
      perceived social support matter?
AB  - Over the past decade there has been increasing interest in the idea that marriage
      and perhaps other forms of interpersonal support can buffer the negative effects
      of poverty. The current study tests the hypothesis that marital status, perceived
      social support and neighborhood collective efficacy can moderate the effects of
      economic adversity on depressive symptoms among parents. Hierarchical Linear
      Modeling was used to analyze data from the Project on Human Development in
      Chicago Neighborhoods. Participants were 1,957 mothers of minor children.
      Analysis of main effects revealed associations between neighborhood SES (beta = 
      0.69, SE (0.15), p < .001), family income (beta = -0.11, SE (0.05), p = .02)
      financial strain (beta = 0.51, SE (0.18), p = .004), being single (beta = 0.63,
      SE (0.24), p = .009) and perceived social support (beta = -0.22, SE (0.03), p <
      .001) on depressive symptoms. The hypothesis that interpersonal resources can
      buffer the effects of economic adversity was not supported. There were no
      significant interactions between marital status and economic adversity. There was
      a significant interaction between perceived social support and neighborhood level
      socioeconomic status (beta = -0.07, SE (0.03), p = .04) but the effects of social
      support were weakest in neighborhoods characterized by low socioeconomic status.

PMID- 24122089
TI  - Molecular species of phospholipids with very long chain fatty acids in skin
      fibroblasts of Zellweger syndrome.
AB  - The ratio of C 26:0/C 22:0 fatty acids in patient lipids is widely accepted as a
      critical clinical criterion of peroxisomal diseases, such as Zellweger syndrome
      and X-linked adrenoleukodystrophy (X-ALD). However, phospholipid molecular
      species with very long chain fatty acids (VLCFA) have not been precisely
      characterized. In the present study, the structures of such molecules in
      fibroblasts of Zellweger syndrome and X-ALD were examined using LC-ESI-MS/MS
      analysis. In fibroblasts from Zellweger patients, a large number of VLCFA
      containing molecular species were detected in several phospholipid classes as
      well as neutral lipids, including triacylglycerol and cholesteryl esters. Among
      these lipids, phosphatidylcholine showed the most diversity in the structures of
      VLCFA-containing molecular species. Some VLCFA possessed longer carbon chains
      and/or larger number of double bonds than C 26:0-fatty acid (FA). Similar VLCFA
      were also found in other phospholipid classes, such as phosphatidylethanolamine
      and phosphatidylserine. In addition, VLCFA-containing phospholipid species showed
      some differences among fibroblasts from Zellweger patients. It appears that
      phospholipids with VLCFA, with or without double bonds, as well as C 26:0-FA
      might affect cellular functions, thus leading to the pathogenesis of peroxisomal
      diseases, such as Zellweger syndrome and X-ALD.

PMID- 24122090
TI  - Autoantibodies isolated from preeclamptic patients induce endothelial dysfunction
      via interaction with the angiotensin II AT1 receptor.
AB  - Complete understanding of the etiology underlying endothelial damage in
      preeclampsia (PE) remains deficient. Recent studies suggest that autoantibodies
      against angiotensin II AT1 receptors (AT1-AA) may affect vascular endothelial
      integrity. However, direct evidence demonstrating association between AT1-AA from
      preeclamptic patients and vascular endothelial injury is lacking. The current
      study determined the effects of AT1-AA isolated from preeclamptic patients (Pre
      IgG) upon the endothelium and attempted to elucidate the underlying mechanisms of
      injury. Pre-IgG markedly induced dose-dependent vasoconstriction in aortic
      vascular rings, an effect blocked by AT1 receptor antagonist losartan. Pre-IgG
      induced vasoconstriction was increased in the absence of intact endothelium (1.59
      +/- 0.04 g vs. 1.63 +/- 0.08 g, P < 0.05). Additionally, Pre-IgG incubation with
      human umbilical vein endothelial cells significantly increased lactate
      dehydrogenase release in a time-dependent manner (0.84 +/- 0.07 vs. 3.50 +/-
      0.09, 24 vs. 72-h exposure group, P < 0.01) and increased caspase-3 and -8
      activities (peaking at 48 h), but did not affect caspase-9 activity. Taken
      together, these results support the contribution of AT1-AA to endothelial cell
      injury and dysfunction in PE. 

PMID- 24122091
TI  - Surgical fidelity: comparing the microscope and the endoscope.
AB  - BACKGROUND: Both the microscope and the endoscope are widely used as
      visualization tools in neurosurgery; however, surgical dexterity when operating
      with each may differ. The aim of this study was to compare the surgical fidelity
      when using each of these visualization tools. METHODS: Junior residents and
      expert surgeons performed standardized motor tasks under microscopic and
      endoscopic visualization. Demerits for inaccuracy and time needed to complete the
      tasks were used to compare the surgeons' performance with the microscope and the
      endoscope. The participants also performed a motor task under direct vision using
      different instruments to evaluate whether the shape of the instrument had any
      impact on the surgical fidelity. RESULTS: For the junior residents, the number of
      demerits accrued was lower with the microscope than with the endoscope, and the
      time needed to complete the tasks was also lower with the microscope. There was
      no difference in the number of demerits between the microscopic and the
      endoscopic experts, but the microscopic expert completed the task in a shorter
      time. There was no difference in demerits or performance time when comparing a
      short, straight instrument and a longer, bayoneted one. CONCLUSIONS: For junior
      residents, surgical fidelity is higher with the microscope than with the
      endoscope. This difference vanishes with experience, but a slower speed of
      execution is observed with endoscopic visualization, both in junior and expert
      surgeons.

PMID- 24122092
TI  - Improving average health and persisting health inequities--towards a justice and
      fairness platform for health policy making in Asia.
AB  - BACKGROUND: Following a period of rapid economic and social change across Asia in
      the 1980s and 1990s, there have been persisting reports of public sector health
      systems decline and worsening health inequities within countries. Many studies
      and analyses in the region have indicated that these inequities are socially
      determined, leading to questions regarding the adequacy of current health policy
      approaches towards addressing the challenge of persisting health inequities.
      METHODS: Utilizing published data from Demographic Health Surveys (DHS) and case
      studies and reviews on health inequity in the Asian region, this article aims to
      describe the existing patterns of inequity of health access both within and
      between countries, focusing on immunization, maternal health access, nutritional
      outcomes and child mortality, with a view to recommending health policy options
      for addressing these health inequities. We compare the gap in access and outcomes
      between the highest and the lowest wealth quintiles, as well as cross-reference
      these findings with case studies and surveys on health inequities in the region.
      RESULTS: In Asia, while in terms of aggregate health more of the poor are being
      reached, the reduction in the gap between social groups in some cases is
      stagnating, particularly for maternal health access and childhood stunting.
      Inequity gaps for immunization are persisting, and remain very wide in large
      population countries. For child mortality, more of the poor are surviving,
      although the rate of mortality decline is more rapid in higher than lower socio
      economic groupings. CONCLUSIONS: Both a strategic shift towards public health
      critique of social and political policy and operational shifts in health
      management and practice will be required to attain improvements in distributive
      health in Asia.

PMID- 24122093
TI  - The best surgical approach for perforated gastric cancer: one-stage vs. two-stage
      gastrectomy.
AB  - BACKGROUND: Surgery for perforated gastric cancer has a dual purpose: treating
      life-threatening peritonitis and curing gastric cancer. An emergent one-stage
      gastrectomy may place an undue burden on patients with a poor general status and
      could impair long-term survival even if the gastric malignancy is curable. A two
      stage gastrectomy, in which the initial treatment of peritonitis is followed by
      elective gastrectomy, can accomplish both desired purposes. METHODS: We
      retrospectively analyzed 514 Japanese cases of perforated gastric cancer. 376
      patients underwent a one-stage gastrectomy and 54 patients underwent a two-stage
      gastrectomy. We evaluated patient characteristics, surgical outcomes,
      postoperative complications, and survival rates in both groups. RESULTS: The two
      stage gastrectomy group saw a 78.4% rate of curative R0 resection and 1.9%
      hospital mortality rate, while corresponding rates in the one-stage gastrectomy
      group were 50 and 11.4%, respectively. Among cases in which curative R0 resection
      was performed, there was no significant difference in overall survival between
      136 one-stage gastrostomies and 40 two-stage gastrostomies. In a multivariate
      analysis, curative R0 resection [hazard ratio (HR) 2.937, p = 0.001] and depth of
      tumor invasion (HR 1.179, p = 0.016) were identified as independent prognostic
      factors. CONCLUSIONS: Regardless of whether patients underwent a one-stage or two
      stage gastrectomy, curative R0 resection improved survival in patients with
      perforated gastric cancer. When curative R0 resection cannot be performed in the
      initial treatment phase due to diffuse peritonitis, non-curative and palliative
      gastrectomy should be avoided, and a two-stage gastrectomy should be planned
      following peritonitis recovery and detailed examinations.

PMID- 24122094
TI  - Image-guided intensity-modulated radiotherapy for patients with locally advanced
      gastric cancer: a clinical feasibility study.
AB  - BACKGROUND: The aim of this study was to determine the medical and technical
      feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic
      gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy.
      METHODS AND MATERIALS: A prospective nonrandomized phase II trial was performed
      on 25 consecutive patients with gastric cancer with high risk (T3-4, N1-3, G2-3,
      R0-1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique.
      Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m(2) was administered as a
      continuous intravenous infusion. Primary endpoints were acute gastrointestinal
      toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning
      and radiation delivery. RESULTS: Early acute events were defined as clinical and
      chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By
      definition, 90 days after the end of IMRT has been evaluated as acute-phase
      toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3
      toxicity occurred in two patients (8%) with diarrhea and in one case (4%) with
      nausea. Hematological changes with grade 3 occurred in three cases (12%) with
      hemoglobin decrease, in five cases (25%) as leukopenia, and in one case (4%) with
      thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume
      exceeding 30 Gy (V30) was 21%. Mean dose for right and left kidney was 9 and 13
      Gy, respectively, and V20 was 9% and 13%, respectively. Heart received a median
      dose of 15 Gy and V40 was 17%. The mean dose to the bowel was 11 Gy and V40 was
      6%. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution,
      including the coverage, for the target region were as follows: minimum was 33 Gy,
      maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99%
      and 95% of planning target volume (OTV) in 66% and 92% of cases, respectively.
      Median PTV was 15.77 ml (range, 805-3,604 ml). CONCLUSIONS: The data support the
      practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer
      in the postoperative setting as a proof of principle. Acute toxicity has been
      tolerable.

PMID- 24122096
TI  - Adsorption kinetic process of thiol ligands on gold nanocrystals.
AB  - Understanding the kinetic mechanism during ligand adsorption on gold nanocrystals
      is important for designing and fine-tuning their properties and implications.
      Here, we report a kinetic study on the adsorption process of dodecanethiol
      ligands on Au nanocrystals of 3.3 nm by an in situ time-resolved X-ray absorption
      fine structure technique. A two-step process of dodecanethiol adsorption on Au NC
      surfaces is proposed based on the obtained ligand coverage, which shows a quick
      increase from 0 to 0.40 within the first 20 min, followed by a much slower
      increase to the limiting value of 0.94. In-depth analysis suggests that the first
      stage involves the quick adsorption of dodecanethiol to the corner and edge sites
      of Au NCs surfaces, leading to remarkable surface Au-Au bond length relaxation
      (from 2.79 to 2.81 A) and pronounced gold-to-ligand charge transfer. The second
      step that corresponds to the much slower adsorption process to the surface facets
      could be described by the Langmuir kinetics equation with an adsorption rate
      constant of 0.0132 min(-1) and an initial coverage of 0.41, in good agreement
      with the initially preferable adsorption of thiols to the most favorable sites. 

PMID- 24122095
TI  - Urinary 1-hydroxypyrene as a comprehensive carcinogenic biomarker of exposure to
      polycyclic aromatic hydrocarbons: a cross-sectional study of coke oven workers in
      China.
AB  - PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are multiple compounds that
      include many carcinogens. We conducted a cross-sectional study in steel plant
      workers in Anshan, China, to identify biomarkers that reflect the carcinogenicity
      of PAHs. METHODS: Subjects were 57 workers and 20 controls. Level of personal
      exposure to PAHs was measured using GC-MS. In accordance with the assessment
      methods defined by the United States Environmental Protection Agency (US EPA), 15
      PAHs were selected for the analysis. For the measurement of urinary metabolites,
      urine samples were treated with beta-glucuronidase and analyzed using HPLC with a
      fluorescence detector. RESULTS: The mean range of personal exposure to 15 PAHs
      (total PAHs) was 178.85, 47.08-1,329.45 (geometric mean, 5th and 95th percentile)
      MUg/m(3). Ten known urinary metabolites (1-hydroxynaphthalene, 2
      hydroxynaphthalene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3
      hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 3
      hydroxybenz[a]anthracene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene) and
      four unknown peaks were detected. The highest correlation was between total PAHs
      and urinary 2-hydroxynaphthalene (Spearman r = 0.716, P < 0.01). Among the
      detected urinary metabolites, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3
      hydroxyphenanthrene, and 1-hydroxypyrene were found to correlate significantly
      with the "Sigma carcinogenic potency of PAHs" (sum of seven carcinogenic PAHs
      calculated from the levels of personal PAHs and relative potency factors), and
      with the greatest correlation found for 1-hydroxypyrene (Spearman r = 0.630, P <
      0.01). CONCLUSIONS: The analysis of personal exposure to 15 PAHs and 10 urinary
      metabolites, and calculation of Sigma carcinogenic potency, indicated that
      urinary 1-hydroxypyrene was the most comprehensive carcinogenic biomarker of
      exposure to PAHs.

PMID- 24122097
TI  - Rising temperatures and dwindling water supplies? Perception of climate change
      among residents of the Spanish Mediterranean tourist coastal areas.
AB  - In this article, we discuss the results of a survey on the perception of climate
      change in the 14 "tourist zones" (as defined by the Spanish Statistical
      Institute, INE) that stretch from the French border to Gibraltar alongside the
      Spanish Mediterranean coast, including the Balearic Islands. Our sample consisted
      of 1,014 telephone interviews stratified according to the number of tourists
      staying in each zone. Respondents showed concern for the likely impacts of
      climate change on jobs and thought that climate change would reduce the economic
      activity of their areas. Responses were also pessimistic regarding future water
      availability but agreed with the development of alternative sources such as
      desalination and water re-use. Household size, educational levels, and employment
      tended to be the most significant statistical explanatory factors regarding
      attitudes toward climate change. Respondents in larger households (a variable not
      tested in the literature as far as we know), respondents with higher education,
      and respondents working for a wage tended to express more concerns than the rest.

PMID- 24122098
TI  - Potential impacts and management implications of climate change on Tampa Bay
      estuary critical coastal habitats.
AB  - The Tampa Bay estuary is a unique and valued ecosystem that currently thrives
      between subtropical and temperate climates along Florida's west-central coast.
      The watershed is considered urbanized (42 % lands developed); however, a suite of
      critical coastal habitats still persists. Current management efforts are focused
      toward restoring the historic balance of these habitat types to a benchmark 1950s
      period. We have modeled the anticipated changes to a suite of habitats within the
      Tampa Bay estuary using the sea level affecting marshes model under various sea
      level rise (SLR) scenarios. Modeled changes to the distribution and coverage of
      mangrove habitats within the estuary are expected to dominate the overall
      proportions of future critical coastal habitats. Modeled losses in salt marsh,
      salt barren, and coastal freshwater wetlands by 2100 will significantly affect
      the progress achieved in "Restoring the Balance" of these habitat types over
      recent periods. Future land management and acquisition priorities within the
      Tampa Bay estuary should consider the impending effects of both continued
      urbanization within the watershed and climate change. This requires the
      recognition that: (1) the Tampa Bay estuary is trending towards a mangrove
      dominated system; (2) the current management paradigm of "Restoring the Balance"
      may no longer provide realistic, attainable goals; (3) restoration that creates
      habitat mosaics will prove more resilient in the future; and (4) establishing
      subtidal and upslope "refugia" may be a future strategy in this urbanized estuary
      to allow sensitive habitat types (e.g., seagrass and salt barren) to persist
      under anticipated climate change and SLR impacts.

PMID- 24122099
TI  - Bridging disciplines, knowledge systems and cultures in pest management.
AB  - The success of research in integrated environmental and natural resource
      management relies on the participation and involvement of different disciplines
      and stakeholders. This can be difficult to achieve in practice because many
      initiatives fail to address the underlying social processes required for
      successful engagement and social learning. We used an action research approach to
      support a research-based group with a range of disciplinary and stakeholder
      expertise to critically reflect on their engagement practice and identify lessons
      around how to collaborate more effectively. This approach is provided here as a
      guide that can be used to support reflective research practice for engagement in
      other integration-based initiatives. This paper is set in the context of an
      integrated wildlife management research case study in New Zealand. We illustrate
      how multi-, inter- and trans-disciplinary approaches can provide a framework for
      considering the different conversations that need to occur in an integrated
      research program. We then outline rubrics that list the criteria required in
      inter- and trans-disciplinary collaborations, along with examples of effective
      engagement processes that directly support integration through such efforts.
      Finally, we discuss the implications of these experiences for other researchers
      and managers seeking to improve engagement and collaboration in integrated
      science, management and policy initiatives. Our experiences reaffirm the need for
      those involved in integrative initiatives to attend to the processes of
      engagement in both formal and informal settings, to provide opportunities for
      critical reflective practice, and to look for measures of success that
      acknowledge the importance of effective social process.

PMID- 24122100
TI  - Soil organic carbon stock and distribution in cultivated land converted to
      grassland in a subtropical region of China.
AB  - Land-use change from one type to another affects soil carbon (C) stocks which is
      associated with fluxes of CO2 to the atmosphere. The 10-years converted land
      selected from previously cultivated land in hilly areas of Sichuan, China was
      studied to understand the effects of land-use conversion on soil organic casrbon
      (SOC) sequestration under landscape position influences in a subtropical region
      of China. The SOC concentrations of the surface soil were greater (P?0.001) for
      converted soils than those for cultivated soils but lower (P?0.001) than those
      for original uncultivated soils. The SOC inventories (1.90-1.95 kg m-2) in the 0
      15 cm surface soils were similar among upper, middle, and lower slope positions
      on the converted land, while the SOC inventories (1.41-1.65 kg m-2) in this soil
      layer tended to increase from upper to lower slope positions on the cultivated
      slope. On the whole, SOC inventories in this soil layer significantly increased
      following the conversion from cultivated land to grassland (P?0.001). In the
      upper slope positions, converted soils (especially in 0-5 cm surface soil)
      exhibited a higher C/N ratio than cultivated soils (P = 0.012), implying that
      strong SOC sequestration characteristics exist in upper slope areas where severe
      soil erosion occurred before land conversion. It is suggested that landscape
      position impacts on the SOC spatial distribution become insignificant after the
      conversion of cultivated land to grassland, which is conducive to the
      immobilization of organic C. We speculate that the conversion of cultivated land
      to grassland would markedly increase SOC stocks in soil and would especially
      improve the potential for SOC sequestration in the surface soil over a moderate
      period of time (10 years).

PMID- 24122101
TI  - Immobilization of thermostable beta-galactosidase on epoxy support and its use
      for lactose hydrolysis and galactooligosaccharides biosynthesis.
AB  - Thermoresistant, recombinant beta-galactosidase from Thermotoga maritima was
      purified and immobilized on the surface of epoxy-coated magnetic beads. The
      enzyme, which has hexameric quaternary structure as shown by gel filtration
      chromatography, attaches to the resin through multiple covalent linkages that
      involve different subunits. The bound enzyme shows higher stability than the free
      form. The immobilized enzyme showed to be efficient for the hydrolysis of lactose
      and the biosynthesis of galactooligosaccharides (GOS). The chemical structure of
      synthesized GOS has been determined by NMR revealing that the main product was
      beta-3'-galactosyl lactose. Although beta-galactosidases from different sources
      have been used for the same purposes, the distinct advantage of the methodology
      described in this communication is that the enzyme can be easily produced,
      purified and immobilized in large quantities.

PMID- 24122102
TI  - Personalized medicine in neurodegenerative diseases: how far away?
AB  - Neurodegenerative diseases are characterized by progressive dysfunction of the
      nervous system as a result of neuronal loss in the brain and spinal cord. Despite
      extensive research efforts aimed at development of new disease-modifying
      therapeutics, there is still no effective treatment to halt neurodegenerative
      processes. Thus, modification of current therapeutic and diagnostic research
      strategies is a goal of increasing urgency. The biggest limitation in
      neurodegenerative disease research is the lack of appropriate biomarkers.
      Discovery of universal biomarkers capable of diagnosing patients with
      neurodegenerative diseases, monitoring their response to therapy, and predicting
      disease progression seems to be a tall order. Instead, a combination of different
      methodologies in the discovery of biomarkers specific for each described aspect
      of the disease seems to be a more viable approach. Although application of
      personalized medicine in diagnosis and treatment of neurodegenerative diseases
      may seem far off, some recent developments, such as utilizing specific biological
      therapies in multiple sclerosis, microRNA profiling as a source of novel
      biomarkers in Parkinson's disease, or combination of neuroimaging and proteomic
      analyses in diagnosis of Alzheimer's disease patients, already point to the way
      clinical neurology may integrate new achievements in everyday practice.
      Combination of genomic, proteomic, glycomic, and metabolomic approaches may yield
      novel insights into molecular mechanisms of disease pathophysiology, which could
      then be integrated and translated into clinical neurology. Based on the
      developments during the past decade, it is feasible to predict that a
      personalized approach to treating neurological disorders will become more widely
      applicable in the coming years.

PMID- 24122103
TI  - Postpartum weight retention is associated with elevated ratio of oxidized LDL
      lipids to HDL-cholesterol.
AB  - Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as
      cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present
      study investigated how postpartum weight retention effects on ox-LDL and serum
      lipids. The study is a nested comparative research of a cluster-randomized
      controlled trial, NELLI (lifestyle and counselling during pregnancy). During
      early pregnancy (8-12 weeks) and 1 year postpartum, 141 women participated in
      measurements for determining of plasma lipids: total cholesterol (T-C), LDL
      cholesterol (LDL-C), HDL-cholesterol (HDL-C), triacylglycerols (TAG) and ox-LDL.
      Subjects were stratified into tertiles (weight loss, unaltered weight and weight
      gain groups) based on their weight change from baseline to follow-up. Ox-LDL was
      determined by baseline level of conjugated dienes in LDL lipids. Among the group
      of weight gainers, concentration of TAG reduced less (-0.14 vs. -0.33, p =
      0.002), HDL-C reduced more (-0.31 vs. -0.16, p = 0.003) and ox-LDL/HDL-C ratio
      increased (3.0 vs. -0.2, p = 0.003) when compared to group of weight loss. Both T
      C and LDL-C elevated more (0.14 vs. -0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015)
      and TAG and ox-LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs. -0.68, p =
      0.026) in unaltered weight group compared to weight loss group. The women who
      gained weight developed higher TAG and ox-LDL/HDL-C ratio as compared to those
      who lost weight. Postpartum weight retention of 3.4 kg or more is associated with
      atherogenic lipid profile.

PMID- 24122104
TI  - Importance weighting, expectation fulfilment and satisfaction: an integrative and
      innovative approach to measuring patient satisfaction with hospital stays.

PMID- 24122105
TI  - Polymerase chain reaction for Enterococcus faecalis in drain fluid: the first
      screening test for symptomatic colorectal anastomotic leakage. The Appeal-study:
      analysis of parameters predictive for evident anastomotic leakage.
AB  - PURPOSE: With current diagnostic methods, the majority of patients with
      symptomatic colorectal anastomotic leakage(CAL) is identified approximately 1
      week after operation.The aim of this study is to determine whether real-time
      polymerase chain reaction (RT-PCR) for detection of Escherichia coli and
      Enterococcus faecalis on drain fluid can serve as a screening test for CAL in the
      early postoperative phase. METHODS: All patients included in this multicenter
      prospective observational study underwent left-sided colorectal resection for
      both malignant and benign diseases with construction of an anastomosis. In all
      patients, an intra-abdominal drain was placed during operation. During the first
      five postoperative days, drain fluid was processed for RT-PCR. The quantitative
      results of the RT-PCR on days 2 to 5 were compared to the results of day 1 in
      order to detect concentration changes. RESULTS: In total, 243 patients, with both
      benign and malignant diseases, were included of whom 19 (7.8 %) developed
      symptomatic CAL. An increase in E. coli concentration was found insignificantly
      more patients with CAL on day 4 and 5 [p =0.0004; diagnostic odds ratio (DOR)
      7.9]. For E. faecalis, this result was found for days 2, 3, and 4 (p <0.003) with
      highest DOR on day 3 (31.6). Sensitivity and negative predictive values were 92.9
      and 98.7 %, respectively, virtually ruling out CAL in case of negative test
      results on the third postoperative day. CONCLUSION: Quantitative PCR for E.
      faecalis performed on drain fluid may be an objective, affordable and fast
      screening tool for symptomatic colorectal anastomotic leakage.

PMID- 24122106
TI  - Executive functioning in attention-deficit/hyperactivity disorder: questioning
      the notion of planning deficits with heart rate reactivity.
AB  - This study employed a paired stimulus paradigm to compare phasic changes in heart
      rate among children (age categories 6-8, 9-10, and 11-12) and adults (age
      categories 18-19 and 20-22) with attention-deficit/hyperactivity disorder (ADHD)
      and age-matched controls. A sample of 95 participants (19 ADHD-diagnosed
      children, 34 controls, 20 ADHD-diagnosed adults, and 22 controls) solved a
      planning task, the Tower of London, through 4 levels of difficulty. It was
      hypothesized that groups with ADHD would show greater heart rate acceleration and
      less final deceleration than would controls, and that these heart rate responses
      would change with age and difficulty level as well. Though heart rate differences
      were found among age categories and difficulty levels, none were found between
      participants with ADHD and controls. The lack of ADHD differences are not
      consistent with the behavioral evidence that planning by itself is one of the
      marked executive function deficits in ADHD. Because ADHD differences were not
      evident, the effects either were not present or were smaller than that of
      difficulty level and age. Possible explanations for this lack of difference and
      future directions are discussed. 

PMID- 24122107
TI  - Molecular characterization and phylogenetic analysis of the genome of porcine
      torovirus.
AB  - In this study, we amplified and sequenced the first genome of porcine torovirus
      (PToV SH1 strain). The genome was found to be 28,301 bp in length, sharing 79 %
      identity with Breda virus. It mainly consists of replicase (20,906 bp) and
      structural genes: spike (4,722 bp), membrane (702 bp), hemagglutinin-esterase
      (1,284 bp), and nucleocapsid (492 bp). Sequence alignments and structure
      prediction suggest genetic differences among toroviruses, mainly in NSP1 (papain
      like cysteine proteinase domain). Rooted phylogenetic trees were constructed
      based on the 3C-like proteinase and RNA-dependent RNA polymerase genes. PToV,
      Berne virus and Breda virus were clustered together, forming a separate branch
      from white bream virus that was distant from that of the coronaviruses.

PMID- 24122108
TI  - Detection of grass carp reovirus (GCRV) with monoclonal antibodies.
AB  - Grass carp reovirus (GCRV) is a pathogen that causes hemorrhagic disease of grass
      carp. It is the most serious infectious disease of carp and causes serious losses
      of fingerlings of grass carp and black carp. In this study, a recombinant VP4,
      one of the viral core proteins, was constructed with a histidine tag and
      expressed at a high level in E. coli, and the expressed protein was mainly found
      in the form of inclusion bodies. The expressed VP4 protein was recognized by an
      anti-His-tag monoclonal antibody and goat anti-GCRV serum. Four monoclonal
      antibodies (16B7, 39E12, 13C3 and 14D1) against the recombinant VP4 protein were
      produced. These MAbs did not react with any of the tested viruses or fish cells
      lines in the ELISA tests except GCRV. In western blotting analysis, a protein
      band was observed when the recombinant VP4 protein of GCRV was used as an
      antigen, but a 68-kDa band was observed when natural capsid proteins of GCRV were
      used as antigens. Furthermore, a sandwich ELISA was developed for detection of
      GCRV. The detection limit of the test was 105 TCID50 of GCRV per mL.

PMID- 24122109
TI  - Genetic variability and evolution of broad bean wilt virus 1: role of
      recombination, selection and gene flow.
AB  - Analysis of four genomic regions from 37 geographically diverse isolates of broad
      bean wilt virus 1 (BBWV-1) showed high genetic diversity in comparison to most
      plant viruses. Comparison of synonymous and nonsynonymous substitutions of the
      small coat protein gene (SCP) revealed negative selection for most amino acid
      positions. Phylogenetic analysis of SCP showed that some BBWV-1 isolates from
      distant geographical areas were genetically close, suggesting long-distance
      migration. Analysis of genetic differentiation revealed high gene flow between
      Spanish and Near Eastern subpopulations, which were separated from North-Central
      and South-Eastern European subpopulations. Finally, putative recombinant and
      reassortant genomes were also identified.

PMID- 24122110
TI  - Rapid detection of bovine herpesvirus 1 in bovine semen  by loop-mediated
      isothermal amplification (LAMP) assay.
AB  - Bovine herpesvirus 1 (BoHV-1) is the most common viral pathogen found in bovine
      semen, causing numerous reproductive disorders leading to economic losses to the
      cattle industry. For rapid detection of BoHV-1 in bovine semen, in this study, we
      applied a loop-mediated isothermal amplification (LAMP) assay. The assay could be
      completed within 90 min, including total DNA isolation, target amplification, and
      visual interpretation of positive or negative results with the naked eye. The
      assay detected as little as 10 fg of BoHV-1 DNA per reaction. The analytical
      sensitivity of the assay was 0.2 TCID50 BoHV-1 per reaction, which was 100 times
      more sensitive than conventional PCR and comparable to TaqMan real-time PCR. The
      applicability of the assay was assessed by analysing 118 semen samples collected
      from breeding bulls. On comparison with TaqMan real-time PCR, the LAMP assay had
      a diagnostic sensitivity of 97 %, specificity of 100 %, and accuracy of 99.2 %
      for detection of BoHV-1 in bovine semen. The LAMP assay developed in this study
      is a rapid, sensitive, and cost-effective alternative for detection of BoHV-1 in
      bovine semen.

PMID- 24122111
TI  - Selection and characterization of an acid-resistant mutant of serotype O foot-and
      mouth disease virus.
AB  - Foot-and-mouth disease virus (FMDV) loses infectivity and immunogenicity due to
      its disassembly in culture environments below pH 6.8. To study the molecular
      basis of viral resistance to acid-induced disassembly and improve the acid
      stability of inactivated FMD vaccines during the manufacturing process, type O
      FMDV mutants with increased resistance to acid inactivation were selected, and
      the genes encoding their capsid proteins were sequenced. Three amino acid
      substitutions (VP1 N17D, VP2 D86A, and VP4 S73N) were found in all of the
      mutants. When these substitutions were introduced into seven infectious FMDV
      clones alone or combined, a single amino acid substitution in the VP1 protein,
      N17D, which also appears in type C FMDV acid-resistant mutants, was found to be
      responsible for the increased resistance to acid inactivation for type O FMDV. In
      addition, although viral fitness was reduced under standard culture conditions,
      viral growth kinetics and virulence were not significantly altered in the rescued
      mutant virus rN17D with the VP1 N17D substitution. Importantly, the N17D
      substitution could confer improved immunogenicity to the mutant virus rN17D under
      acidic conditions compared with its parental virus O/YS/CHA/05. These results
      demonstrate that the N17D substitution in VP1 is the molecular determinant of the
      acid-resistant phenotype in type O FMDV, indicating the potential for use of this
      substitution to improve the acid stability of inactivated FMD vaccines during the
      vaccine production process.

PMID- 24122112
TI  - A new endornavirus species infecting Malabar spinach  (Basella alba L.).
AB  - A putative new endornavirus was isolated from Malabar spinach (Basella alba). The
      viral dsRNA consisted of 14,027 nt with a single ORF that coded for a polyprotein
      of 4,508 aa. The genome organization was similar to that of four other
      endornaviruses. Conserved domains for helicase-1, capsular synthase, UDP-glucose
      glycosyltransferase (UGT), and RdRp were detected. Infected plants were
      phenotypically undistinguishable from healthy ones. The name Basella alba
      endornavirus is proposed for the virus isolated from Malabar spinach.

PMID- 24122113
TI  - Glyphosate-based herbicide has contrasting effects on prey capture by two co
      occurring wolf spider species.
AB  - Anthropogenic substances have the potential to affect animal behavior either
      because they present a novel stimulus or because they interfere with natural
      chemical communication pathways. Such shifts can alter the dynamic between
      predators and potential prey, which might affect population success as well as
      the strength of food web linkages. We examined the foraging of two wolf spiders,
      Tigrosa helluo and Pardosa milvina (Araneae, Lycosidae), that are abundant in
      agroecosystems where they are routinely exposed to herbicides. We tested the
      hypothesis that the presence of a commercial formulation of a glyphosate-based
      herbicide would affect the prey capture behavior of these two wolf spiders. We
      tested the larger Tigrosa foraging on Pardosa or crickets (Acheta domesticus) and
      the smaller Pardosa foraging on crickets. Tigrosa subdued crickets more quickly
      and with fewer lunges than it took them to capture Pardosa. The presence of
      herbicide allowed Tigrosa to orient toward and capture both prey species more
      quickly but it did not affect the number of lunges required to subdue either
      prey. Herbicide did not affect the timing of prey capture for Pardosa but it did
      cause them to use more lunges in the process. Thus, herbicide had contrasting
      effects on foraging behavior of these two agrobiont predators, which means that
      it could shift the direction and strength of food web linkages in complex ways.

PMID- 24122114
TI  - Revisiting the TRAK family of proteins as mediators of GABAA receptor
      trafficking.
AB  - gamma-Aminobutyric acid type A (GABAA) receptor interacting factor-1 (GRIF-1) was
      originally discovered as a result of studies aiming to find the elusive GABAA
      receptor clustering protein. It was identified as a GABAA receptor associated
      protein by virtue of its specific interaction with the GABAA receptor beta2
      subunit intracellular loop in a yeast two-hybrid screen of a rat brain cDNA
      library. Further work however, established that GRIF-1, now known as trafficking
      kinesin protein 2 (TRAK2), is a member of the TRAK family of kinesin adaptor
      proteins. A pivotal role for TRAK1 and TRAK2 in the transport of mitochondria is
      well recognized. Notwithstanding this progress, there is a body of evidence that
      still supports a role for TRAKs in the intracellular transport of GABAA
      receptors. This is critically reviewed in this article. 

PMID- 24122115
TI  - Control of Aedes albopictus with attractive toxic sugar baits (ATSB) and
      potential impact on non-target organisms in St. Augustine, Florida.
AB  - The purpose of this study was to test the efficacy of bait stations and foliar
      applications containing attractive toxic sugar baits (ATSB) and eugenol to
      control Aedes albopictus. At the same time, the potential impact of these control
      methods was evaluated on non-target organisms. The study was conducted at five
      tire sites in St. Augustine, Florida. A. albopictus populations were
      significantly reduced with ATSB-eugenol applications applied directly to non
      flowering vegetation and as bait stations compared with non-attractive sugar
      baits and control. The application of ATSB made to non-flowering vegetation
      resulted in more significant reductions of mosquito populations compared to the
      application of ATSB presented in a bait station. Over 5.5% of the non-targets
      were stained in the flowering vegetation application site. However, when the
      attractive sugar bait application was made to non-flowering vegetation or
      presented in bait stations, the impact on non-target insects was very low for all
      non-target orders as only 0.6% of the individual insects were stained with the
      dye from the sugar solutions, respectively. There were no significant differences
      between the staining of mosquitoes collected in flowering vegetation (206/1000)
      or non-flowering vegetation (242/1000) sites during the non-target evaluation.
      Our field studies support the use of eugenol as an active ingredient for
      controlling the dengue vector A. albopictus when used as an ATSB toxin and
      demonstrates potential use in sub-tropical and tropical environments for dengue
      control.

PMID- 24122116
TI  - Influence of blood donation on the incidence of plateau at VO2max.
AB  - PURPOSE: The purpose of this study was to examine the effects of reductions in
      blood volume and associated oxygen-carrying capacity on the incidence of plateau
      at VO2max. METHODS: Fifteen well-trained athletes (age 23.3 +/- 4.5; mass 77.4 +/
      13.1 kg, height 180.1 +/- 6.0 cm) completed three incremental cycle tests to
      volitional exhaustion, of which the first was defined as familiarisation, with
      the remaining two trials forming the experimental conditions of pre- (UBL) and
      post-(BLE) blood donation (~ 450 cm(3)). The work rate for the incremental tests
      commenced at 100 W for 60 s followed by a ramp of 0.42 W s(-1), with cadence
      being held constant at 80 rpm. Throughout all trials, VO2 was determined on a
      breath-by-breath basis using a pre-calibrated metabolic cart. The criteria for
      plateau determination was a ?VO2 <= 50 ml min(-1) over the final two consecutive
      30 s sampling periods. RESULTS: Despite a significant (P = 0.0028) 9.4 %
      reduction in haemoglobin concentration and 10.8 % (P = 0.016) reduction in
      erythrocyte count between UBL and BLE, there was no change in plateau incidence.
      However, significant differences were observed for both VO2max (P = 0.0059) 51.3
      +/- 7.6 (UBL) 48.4 +/- 7.9 ml kg(-1) min(-1) (BLE) and gas exchange threshold
      arrival time 383.4 +/- 85.2 s (UBL) 349.2 +/- 71.4 s (BLE) (P = 0.0028).
      CONCLUSION: These data suggest that plateau at VO2max is unaffected by O2
      availability lending support to the notion of the plateau being dependent on the
      anaerobic capacity and the classically orientated concept of VO2max.

PMID- 24122117
TI  - Caldimonas meghalayensis sp. nov., a novel thermophilic betaproteobacterium
      isolated from a hot spring of Meghalaya in northeast India.
AB  - While studying the microbial diversity of hot springs of North-east India we
      isolated a strain AK31T from the Jakrem hot spring of Meghalaya. The strain
      formed light yellow colonies on nutrient agar and was Gram negative, non spore
      forming rods, motile with single polar flagellum. The strain was positive for
      oxidase and catalase and hydrolysed starch and weakly urea. The predominant
      cellular fatty acids were C16:0 (34.8 %), C17:0 cyclo (27.1 %), C16:1 omega7c
      and/or iso-C15:0 2OH (summed feature 3) (9.6 %), C10:0 3OH (8.0 %), C12:0 (5.8
      %), C14:0 (5.3 %) and C18:1 omega7c (5.3 %). Strain AK31T contained ubiquinone-8
      as the major respiratory quinone and diphosphatidylglycerol,
      phosphatidylethanolamine, three unidentified phospholipids and one unidentified
      glycolipid as the polar lipids. The G + C content of the DNA of the strain AK31T
      was 66.7 mol%. The 16S rRNA gene sequence analysis indicated that strain AK31T
      was member of the genus Caldimonas and closely related to Caldimonas
      manganoxidans JCM 10698T and Caldimonas taiwanensis On1T with 96.9 % similarity
      and with Aquincola tertiaricarbonis L10T and Azohydromonas australica IAM 12664T
      with 96.5 and 96.4 % similarity respectively. Phylogenetic analyses indicated
      that the strain AK31T clustered with C. manganoxidans JCM 10698T and C.
      taiwanensis On1T with a phylogenetic distance of 3.25 %. Based on data from the
      current polyphasic study, strain AK31T is proposed as a novel species of the
      genus Caldimonas, for which the name Caldimonas meghalayensis sp. nov. is
      proposed. The type strain of C. meghalayensis is AK31T (= MTCC 11703T = JCM
      18786T).

PMID- 24122118
TI  - Fontibacillus phaseoli sp. nov. isolated from Phaseolus  vulgaris nodules.
AB  - A bacterial strain, designated BAPVE7BT, was isolated from root nodules of
      Phaseolus vulgaris in Spain. Phylogenetic analysis based on its 16S rRNA gene
      sequence placed the isolate into the genus Fontibacillus with Fontibacillus
      panacisegetis KCTC 13564T its closest relative with 97.1 % identity. The isolate
      was observed to be a Gram-positive, motile and sporulating rod. The catalase test
      was negative and oxidase was weak. The strain was found to reduce nitrate to
      nitrite and to produce beta-galactosidase but the production of gelatinase,
      caseinase, urease, arginine dehydrolase, ornithine or lysine decarboxylase was
      negative. Acetoin production and aesculin hydrolysis were found to be positive.
      Growth was observed to be supported by many carbohydrates and organic acids as
      carbon source. MK-7 was identified as the predominant menaquinone and the major
      fatty acid (43.7 %) as anteiso-C15:0, as occurs in the other species of the genus
      Fontibacillus. Strain BAPVE7BT displayed a complex lipid profile consisting of
      diphosphatidylglycerol, phosphatidylglycerol, four glycolipids, four
      phospholipids, two lipids, two aminolipids and an aminophospholipid.
      Mesodiaminopimelic acid was detected in the peptidoglycan. The G+C content was
      determined to be 45.6 mol% (Tm). Phylogenetic, chemotaxonomic and phenotypic
      analyses showed that strain BAPVE7BT should be considered a new species of genus
      Fontibacillus, for which the name Fontibacillus phaseoli sp. nov. is proposed
      (type strain, LMG 27589T, CECT 8333T).

PMID- 24122119
TI  - Mutants of the pentose-fermenting yeast Pachysolen tannophilus tolerant to
      hardwood spent sulfite liquor and acetic acid.
AB  - A strain development program was initiated to improve the tolerance of the
      pentose-fermenting yeast Pachysolen tannophilus to inhibitors in lignocellulosic
      hydrolysates. Several rounds of UV mutagenesis followed by screening were used to
      select for mutants of P. tannophilus NRRL Y2460 with improved tolerance to
      hardwood spent sulfite liquor (HW SSL) and acetic acid in separate selection
      lines. The wild type (WT) strain grew in 50 % (v/v) HW SSL while third round HW
      SSL mutants (designated UHW301, UHW302 and UHW303) grew in 60 % (v/v) HW SSL,
      with two of these isolates (UHW302 and UHW303) being viable and growing,
      respectively, in 70 % (v/v) HW SSL. In defined liquid media containing acetic
      acid, the WT strain grew in 0.70 % (w/v) acetic acid, while third round acetic
      acid mutants (designated UAA301, UAA302 and UAA303) grew in 0.80 % (w/v) acetic
      acid, with one isolate (UAA302) growing in 0.90 % (w/v) acetic acid. Cross
      tolerance of HW SSL-tolerant mutants to acetic acid and vice versa was observed
      with UHW303 able to grow in 0.90 % (w/v) acetic acid and UAA302 growing in 60 %
      (v/v) HW SSL. The UV-induced mutants retained the ability to ferment glucose and
      xylose to ethanol in defined media. These mutants of P. tannophilus are of
      considerable interest for bioconversion of the sugars in lignocellulosic
      hydrolysates to ethanol.

PMID- 24122120
TI  - Subclinical hypothyroidism in pregnancy: to treat or not to treat.

PMID- 24122121
TI  - Lack of sensorial innervation in the newborn female rats affects the activity of
      hypothalamic monoaminergic system and steroid hormone secretion during puberty.
AB  - There is evidence that sensory innervation plays a role regulating ovarian
      functions, including fertility.Since sensory denervation by means of capsaicin in
      newborn female rats results in a lower response togonadotropins, the present
      study analyzed the effects that sensory denervation by means of capsaicin in
      neonatal rats has on the concentration of monoamines in the anterior(AH) and
      medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of
      newborn female rats were injected subcutaneously with capsaicin and killed at 10,
      20, and 30 days of age and on the first vaginal estrous.The concentrations of
      noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH
      were measured using HPLC, and the levels of estradiol (E),progesterone (P),
      testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The
      results show thatat 20 days of age, capsaicin-treated rats have
      lowernoradrenergic and serotonergic activities in the AH, and that the
      dopaminergic activity was lower in the MH. These results suggest that the
      sensorial system connections within the monoaminergic systems of the AH and MH
      are different.Capsaicin-treated animals had lower T, E, and P levels than in the
      control group, suggesting that the lower activity in the AH monoaminergic system
      and lower hormonesecretion could be explained by the blockade of information
      mediated by the sensory innervation (probably substance P), mainly between the
      ovary and the AH.

PMID- 24122122
TI  - Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib
      administration as predictors of survival for advanced hepatocellular carcinoma.
AB  - BACKGROUND: A new predictive biomarker for determining prognosis in patients with
      hepatocellular carcinoma (HCC) who receive sorafenib is required, because
      achieving a reduction in tumor size with sorafenib is rare, even in patients who
      have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is
      a sorafenib target. In the current study, the authors examined changes in plasma
      VEGF concentrations during sorafenib treatment and determined the clinical
      significance of VEGF as a prognostic indicator in patients with HCC. METHODS:
      Plasma VEGF concentrations were serially measured in 63 patients with advanced
      HCC before and during sorafenib treatment. A plasma VEGF concentration that
      decreased >5% from the pretreatment level at 8 weeks was defined as a "VEGF
      decrease." An objective tumor response was determined using modified Response
      Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and
      every 3 months thereafter. RESULTS: Patients who had a VEGF decrease at week 8
      (n=14) had a longer median survival than those who did not have a VEGF decrease
      (n=49; 30.9 months vs 14.4 months; P=.038). All patients who had a VEGF decrease
      survived for >6 months, and the patients who had both a VEGF decrease and an
      alpha-fetoprotein response (n=6) survived during the observation period (median,
      19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease,
      radiologic findings classified as progressive disease, and major vascular
      invasion were associated significantly with 1-year survival; and, in multivariate
      analysis, a VEGF decrease was identified as an independent factor associated
      significantly with survival. CONCLUSIONS: A plasma VEGF concentration decrease at
      8 weeks after starting sorafenib treatment may predict favorable overall survival
      in patients with advanced HCC.

PMID- 24122124
TI  - The study of rare earth elements in farmer's well waters of the Podwisniowka acid
      mine drainage area (south-central Poland).
AB  - The principal objective of the current study was to elucidate the potential
      influence of acid mine drainage (AMD) pond on neighboring farmer's wells in the
      Podwisniowka area (south-central Poland), using North American Shale Composite
      (NASC)-normalized rare earth element (REE) concentration profiles. The well
      waters generally displayed a distinctly positive Eu anomaly similar to that of
      parent rocks and AMD sediment. In contrast, the AMD pit pond water exhibited the
      typical roof-shaped NASC-normalized REE concentration pattern with a strong
      positive Gd anomaly. The low pH (mean of 2.9) of this pond water is induced by
      oxidation of pyrite that occurs in quartz veins and rocks exposed in the
      abandoned Podwisniowka quarry. The principal source of REEs in turn is a
      crandallite series of aluminum-phosphate-sulfate (APS) minerals (gorceixite with
      florencite and Ce-bearing goyazite) that prevail in most clayey shales. These
      data indicate that the REE contents of the AMD pit pond and well waters are
      linked to bedrock mineralogy and lithology, but not to pyrite mineralization. The
      diverse REE patterns of NASC-normalized REE concentrations of the AMD and well
      waters may suggest complex sorption and desorption processes that occur at the
      rock-water interface influenced by different pH, Eh, temperature, and other
      factors. This is evidenced by a presence of strong positive Ce anomaly in the
      rocks, a lack of Ce anomaly in the AMD water and sediment, and the dominant
      negative anomaly of this element in the well waters. Variations in correlation
      coefficients (r 2) of REE concentrations between the rocks and the well waters
      may also result from a different contribution of quartzites, clayey shales, or
      tuffites to the REE signal of well waters as well as from mixing of shallow
      groundwater with infiltrating rainwater or meltwater with different REE profiles.

PMID- 24122123
TI  - Transcriptome profiling reveals insight into distinct immune responses to
      Aeromonas salmonicida in gill of two rainbow trout strains.
AB  - The fish gills represent a crucial organ for the communication with the aquatic
      environment. Transcriptional changes in gills of two hatchery rainbow trout
      strains in response to injection with the potent pathogen Aeromonas salmonicida
      were detected by global gene expression profiling using a 4*44K oligonucleotide
      microarray. Emphasis was placed on "day 3 postinfection" representing a decisive
      time point for the resolution of inflammation. The comparison of features and
      pathways differentially regulated in branchial tissues revealed that the local
      breeding strain BORN and imported American rainbow trout apply common and
      specific immune strategies. In gills of infected BORN trout, we observed a
      dynamic regulation of genes controlling NF-kappaB pathways and the induction of
      factors promoting the development of myeloid cells, whereas an increased
      expression of lysozyme and immunoglobulin genes was obvious in gills of infected
      import trout. In order to prove the relevance of the array-predicted candidates
      as well as well-known immune genes for gill immunity, a subsequent in vitro
      experiment was conducted. Altogether, we uncovered dynamic but moderate changes
      in the expression of a broad range of immune-relevant features implying the
      gill's involvement in pathogen defense strategies.

PMID- 24122125
TI  - Pathogenicity of Beauveria bassiana isolated from Moroccan Argan forests soil
      against larvae of Ceratitis capitata (Diptera: Tephritidae) in laboratory
      conditions.
AB  - The Mediterranean fruit fly, Ceratitis capitata Wiedemann (Diptera: Tephritidae),
      is the major tephritid pest in Morocco. This pest survives in Moroccan forests
      Argania spinosa and continually invades the nearest agricultural areas.
      Entomopathogenic fungi are an interesting tool for fruit fly control and hold a
      useful alternative to conventional insecticides. However, primary selection of
      effective pathogens should be taken in laboratory condition prior to applying
      them in the field. Here, we used third late instar larvae of C. capitata to
      investigate the effectiveness of 15 local Beauveria bassiana isolates. Results
      showed that all isolates were able to infect the larval stage, producing a large
      mortality rate in puparia ranging from 65 to 95 % and caused significant
      reduction in adult emergence. The fungal treatments revealed that the mycosis
      occurred also in adults escaping infection as pupariating larvae. The percentage
      of mycosed puparia was highest in strain TAM6.2 (95 %) followed by ERS4.16 (90
      %), therefore they were the most virulent. Median lethal concentration (LC50) was
      studied for five isolates at four concentrations ranging from 105 to 108 conidia
      ml-1. The results showed that the slopes of regression lines for B. bassiana
      ERS4.16 (slope = 0.386) and TAM6.2 (slope = 0.41) were the most important and had
      the lowest LC50 values (2.85 * 103 and 3.16 * 103 conidia ml-1 respectively).
      This investigation suggests that the soil of Argan forests contains pathogenic B.
      bassiana isolates and highlights for the first time their potential as biological
      control toward C. capitata larval stage in Morocco.

PMID- 24122128
TI  - Strong anti-ice ability of nanohairs over micro-ratchet structures.
AB  - A strong anti-ice property of nanohairs over micro-ratchet surfaces is observed.
      A long freezing delay of more than 185 min is achieved for a droplet on the
      nanohairs over ratchet structure with a period of ~290 MUm under -10  degrees C,
      which is attributed to the effective cooperation of the nano- and
      microstructures. 

PMID- 24122126
TI  - Universal Probe Library based real-time PCR for rapid detection of bacterial
      pathogens from positive blood culture bottles.
AB  - A set of real-time PCR based assays using the locked nucleic acid probes from
      Roche Universal ProbeLibrary were developed for rapid detection of eight
      bacterial species from positive blood culture bottles. Four duplex real-time PCR
      reactions targeting to one Gram-positive bacterium and one Gram-negative
      bacterium were optimized for species identification according to Gram stain
      results. We also included mecA-specific primers and probes in the assays to
      indicate the presence of methicillin resistance in the bacterial species. The
      analytical sensitivity was in the range of 1-10 CFU per PCR reaction mixture. The
      specificity and cross reactivity of the assay was validated by 28 ATCC reference
      strains and 77 negative blood culture specimens. No cross-reactivity was observed
      in these samples thus demonstrating 100 % specificity. 72 previously
      characterized clinical isolates were tested by the real-time PCR assay and
      validated the accuracy and feasibility of the real-time PCR assay. Furthermore,
      55 positive blood culture samples were tested using real-time PCR and 50 (90.9 %)
      of them were identified as the same species as judged by biochemical analysis. In
      total, real-time PCR showed 98.2 % consistent to that of traditional methods.
      Real-time PCR can be used as a supplement for early detection of the frequently
      occurred pathogens from the positive blood cultures.

PMID- 24122127
TI  - Fermentation of ginseng extracts by Penicillium simplicissimum GS33 and anti
      ovarian cancer activity of fermented products.
AB  - A total of 58 isolates of beta-glucosidase-producing microorganisms were isolated
      from soil around the wild ginseng roots under forest using Esculin-R2A agar.
      Among these isolates, strain GS33 showed a strong ability to convert ginsenosides
      Rb1, Rb2, Rc, and Rd into F2, Rg3, C-K, and convert ginsenoside Rg1 into Rh1, and
      F1. Fermented ginseng products can inhibit ES-2 cells growth and the IC50 value
      was 0.73 mg ml-1. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the strain GS33 belongs to the genus Penicillium and is most
      closely related to Penicillium simplicissimum (99 %).

PMID- 24122129
TI  - The emergence, growth and decline of political priority for newborn survival in
      Bolivia.
AB  - Bolivia is expected to achieve United Nations Millennium Development Goal Four,
      reducing under-five child mortality by two-thirds between 2021 and 2025. However,
      progress on child mortality reduction masks a disproportionately slow decline in
      newborn deaths during the 2000s. Bolivia's neonatal mortality problem emerged on
      the policy agenda in the mid-1990s and grew through 2004 in relationship to
      political commitments to international development goals and the support of a
      strong policy network. Network status declined later in the decade. This study
      draws upon a framework for analysing determinants of political priority for
      global health initiatives to understand the trajectory of newborn survival policy
      in Bolivia from the early 1990s. A process-tracing case study methodology is
      used, informed by interviews with 26 individuals with close knowledge of newborn
      survival policy in the country and extensive document analysis. The case of
      newborn survival in Bolivia highlights the significance of political commitments
      to international development goals, health policy network characteristics
      (cohesion, composition, status and key actor support) and political transitions
      and instability in shaping agenda status, especially decline-an understudied
      phenomenon considering the transitory nature of policy priorities. The study
      suggests that the sustainability of issue attention therefore become a focal
      point for health policy networks and analyses. 

PMID- 24122130
TI  - Methods of recording theatre activity across publicly funded  hospitals in
      Ireland.
AB  - BACKGROUND: A review of theatre activity in all Health Service Executive (HSE)
      hospitals in Cork and Kerry in 2008 required a manual extraction of theatre
      activity data from largely paper-based log books. A key data management
      recommendation suggested that "a standardised computerised theatre log book
      system be developed in all hospitals in the region". HSE (2010) Reconfiguration
      of health services for Cork and Kerry-theatre utilisation review. ISBN 978-1
      906218-54-6. MATERIALS AND METHODS: In 2010, a computerised minimum dataset
      project group conducted a telephone survey of theatre managers nationally to
      determine the methods of recording theatre activity across publicly funded
      hospital theatres in Ireland. RESULTS: Sixty-one percent of acute hospitals
      nationally did not have a computerised theatre register. Of those who did, 15 %
      had a fully electronic system, 13 % had a dual paper-based and electronic system
      and 7 % had a single surgical specialty system. The HSE South region was
      significantly deprived of an electronic operating system in comparison to other
      HSE regions. While the total number of fully computerised hospital theatres
      remained small,they still dealt with the greater number of hospital discharges
      nationally. CONCLUSIONS: The roll-out of the productive operating theatre
      programme is facilitating the implementation of operating room management systems
      on a phased basis nationally. This will greatly facilitate audit,
      research,patient care and theatre efficiencies.

PMID- 24122133
TI  - [Neoadjuvant chemotherapy for locally advanced colon cancer : Initial results of
      the FOxTROT study.]

PMID- 24122132
TI  - Cellular mechanisms in intermittent hypoxia-induced cardiac damage in vivo.
AB  - Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during
      sleep, is increasingly recognized as an independent risk factor of cardiovascular
      diseases. OSA is associated with changes in the levels of circulating oxidative
      stress/inflammatory markers and dyslipidemia, supporting their mediating roles in
      cardiovascular pathogenesis. Our aims were to investigate the effect of IH on
      heart tissue using an IH-exposed rat model and to explore the potential
      mechanisms involved in the occurrence of cardiac damage. Male Sprague-Dawley rats
      were exposed to IH and intermittent normoxia as control and sacrificed after 2 or
      4 weeks. IH for 4 weeks caused elevation in serum malondialdehyde and cytokine
      induced neutrophil chemoattractant-1 and reduction in serum adiponectin levels.
      In contrast, cardiac oxidative stress and pro-inflammatory markers were
      suppressed while cardiac adiponectin and cholesterol levels were elevated after
      IH exposure for 4 weeks. In parallel, there was an increase in apoptosis in the
      heart of IH-exposed rats, demonstrated by elevations of Bax and cleaved caspase-3
      protein and TUNEL staining. Cardiac damage was further evident with decreased
      arterial vessel and capillary densities, increased cardiac fibrosis, and the loss
      of troponin I. Our data demonstrated that IH exposure paradoxically caused
      systemic oxidative and inflammatory responses and cardioprotective responses,
      i.e., anti-oxidative and anti-inflammatory responses. Despite such a local
      compensatory protective mechanism, cardiac damage was observed that might be due
      to IH-induced cholesterol accumulation in the heart and caspase-dependent
      apoptosis.

PMID- 24122134
TI  - [Risk of malignancy of small hormone inactive pancreatic neuroendocrine tumors.]

PMID- 24122135
TI  - Impact of caregiving experience on mental health  among caregivers: a comparison
      of eating disorder patients  with purging and non-purging behaviors.
AB  - PURPOSE: Differences in mental health among primary caregivers of eating disorder
      patients with purging and non-purging behaviors were explored and predictors of
      psychopathological distress among caregivers were also determined. METHODS: 177
      caregivers, ranging from 29 to 75 years of age, of adults and adolescents with an
      ED participated in the study. The caregivers completed self-report assessments
      related to psychopathological distress (GSI), specific experience of caregiving
      and expressed emotion. Results A statistically significant difference in
      psychopathological distress was presented by caregivers of patients with purging
      behaviors (38.9%) compared with non-purging ones (25%), using a GSI cut-off
      point. In patients who purged, caregiver's intrusiveness and difficulties related
      to eating behavior accounted for 25% of the variance and in those who did not
      purge, difficulties related to eating behavior, guilt, social isolation,
      hostility and negative attitude toward illness accounted for 44% of variance.
      CONCLUSIONS: The differences observed indicate the importance of identifying
      purging as a significant clinical marker of increased risk of psychopathological
      distress in caregivers.

PMID- 24122137
TI  - Neural coupling of cooperative hand movements: a reflex and fMRI study.
AB  - The neural control of "cooperative" hand movements reflecting "opening a bottle"
      was explored in human subjects by electromyographic (EMG) and functional magnetic
      resonance imaging (fMRI) recordings. EMG responses to unilateral nonnoxious ulnar
      nerve stimulation were analyzed in the forearm muscles of both sides during
      dynamic movements against a torque applied by the right hand to a device which
      was compensated for by the left hand. For control, stimuli were applied while
      task was performed in a static/isometric mode and during bilateral synchronous
      pro-/supination movements. During the dynamic cooperative task, EMG responses to
      stimulations appeared in the right extensor and left flexor muscles, regardless
      of which side was stimulated. Under the control conditions, responses appeared
      only on the stimulated side. fMRI recordings showed a bilateral extra-activation
      and functional coupling of the secondary somatosensory cortex (S2) during the
      dynamic cooperative, but not during the control, tasks. This activation might
      reflect processing of shared cutaneous input during the cooperative task.
      Correspondingly, it is assumed that stimulation-induced unilateral volleys are
      processed in S2, leading to a release of EMG responses to both forearms. This
      indicates a task-specific neural coupling during cooperative hand movements,
      which has consequences for the rehabilitation of hand function in poststroke
      patients. 

PMID- 24122136
TI  - Decoding visual object categories in early somatosensory cortex.
AB  - Neurons, even in the earliest sensory areas of cortex, are subject to a great
      deal of contextual influence from both within and across modality connections. In
      the present work, we investigated whether the earliest regions of somatosensory
      cortex (S1 and S2) would contain content-specific information about visual object
      categories. We reasoned that this might be possible due to the associations
      formed through experience that link different sensory aspects of a given object.
      Participants were presented with visual images of different object categories in
      2 fMRI experiments. Multivariate pattern analysis revealed reliable decoding of
      familiar visual object category in bilateral S1 (i.e., postcentral gyri) and
      right S2. We further show that this decoding is observed for familiar but not
      unfamiliar visual objects in S1. In addition, whole-brain searchlight decoding
      analyses revealed several areas in the parietal lobe that could mediate the
      observed context effects between vision and somatosensation. These results
      demonstrate that even the first cortical stages of somatosensory processing carry
      information about the category of visually presented familiar objects. 

PMID- 24122138
TI  - Unreliable evidence: 2 sources of uncertainty during perceptual choice.
AB  - Perceptual decisions often involve integrating evidence from multiple
      concurrently available sources. Uncertainty arises when the integrated (mean)
      evidence fails to support one alternative over another. However, evidence
      heterogeneity (variability) also provokes uncertainty. Here, we asked whether
      these 2 sources of uncertainty have independent behavioral and neural effects
      during choice. Human observers undergoing functional neuroimaging judged the
      average color or shape of a multielement array. The mean and variance of the
      feature values exerted independent influences on behavior and brain activity.
      Surprisingly, BOLD signals in the dorsomedial prefrontal cortex (dmPFC) showed
      polar opposite responses to the 2 sources of uncertainty, with the strongest
      response to ambiguous tallies of evidence (high mean uncertainty) and to
      homogenous arrays (low variance uncertainty). These findings present a challenge
      for models that emphasize the role of the dmPFC in detecting conflict, errors, or
      surprise. We suggest an alternative explanation, whereby evidence is processed
      with increased gain near the category boundary. 

PMID- 24122139
TI  - Binocular stereoscopy in visual areas V-2, V-3, and V-3A of the macaque monkey.
AB  - Over 40 years ago, Hubel and Wiesel gave a preliminary report of the first
      account of cells in monkey cerebral cortex selective for binocular disparity. The
      cells were located outside of V-1 within a region referred to then as "area 18."
      A full-length manuscript never followed, because the demarcation of the visual
      areas within this region had not been fully worked out. Here, we provide a full
      description of the physiological experiments and identify the locations of the
      recorded neurons using a contemporary atlas generated by functional magnetic
      resonance imaging; we also perform an independent analysis of the location of the
      neurons relative to an anatomical landmark (the base of the lunate sulcus) that
      is often coincident with the border between V-2 and V-3. Disparity-tuned cells
      resided not only in V-2, the area now synonymous with area 18, but also in V-3
      and probably within V-3A. The recordings showed that the disparity-tuned cells
      were biased for near disparities, tended to prefer vertical orientations,
      clustered by disparity preference, and often required stimulation of both eyes to
      elicit responses, features strongly suggesting a role in stereoscopic depth
      perception. 

PMID- 24122140
TI  - Rainwater toxicity and contamination study from Sao Paulo Metropolitan Region,
      Brazil.
AB  - Wet deposition is an important process that removes pollutants from the
      atmosphere and transfers them to waters and soil. The goal of this study was to
      assess the biological effects of the atmospheric contamination of rainwater in
      the metropolitan area of Sao Paulo (MASP) using Daphnia similis, Ceriodaphnia
      dubia, and Vibrio fischeri. Experimental assays were carried out according to
      standard toxicity methodology. Twenty-three rainwater samples were collected from
      October 2007 to December 2008, at the Nuclear Research Institute (IPEN), in MASP.
      Major ions were determined by ionic chromatography, which showed NH4(+) and NO3(
      ) as prevalent ions. Ecotoxicological results confirmed toxic potential of
      rainwater, as all samples were toxic to D. similis and C. dubia. The V. fischeri
      luminescence reduction confirmed those negative effects of rainwater and
      percentage inhibition of relative luminescence ranged from 0.2 to 0.9 for 16
      samples. Worse conditions were observed during the rainy season, suggesting
      convective rains are more effective in transferring contaminants and toxicity
      from atmosphere to surface.

PMID- 24122141
TI  - Anthropogenic pollution and variability of manganese in alluvial sediments of the
      Yellow River, Ningxia, northwest China.
AB  - Heavy metal pollution of sediments is a global concern and can be a serious
      problem in heavily industrialized parts of the world. Pollution by manganese is
      particularly common due to its ubiquitous natural occurrence, ease of
      mobilization, and extensive association with industry. In Ningxia, China,
      manganese pollution of Yellow River alluvial sediments was assessed by comparing
      manganese concentrations in 35 sediment samples with background values derived
      from similar sediments obtained at sites considered remote from potential sources
      of contamination. Natural background values of manganese were found to range from
      192 to 323 mg/kg for surface sediments, and from 220 to 325 and 283 to 394 mg/kg
      for subsurface sediments at depths of 45-50 and 95-100 cm, respectively. In the
      study area, manganese content ranged from 565 to 1,363 mg/kg, indicating
      anthropogenic pollution extending to a depth of at least 1 m in the study area.
      All 35 samples were found to exceed the threshold effect concentration (TEC) of
      460 mg/kg, below which adverse effects on sediment-dwelling organisms are not
      expected to occur, and one sample (T12) was found to exceed the probable effect
      concentration (PEC) of 1,100 mg/kg. PEC defines the threshold above which adverse
      effects are likely to be observed. Variogram analysis of the surface sediment
      manganese data revealed adherence to a Gaussian model, and ordinary kriging was
      used to generate a manganese distribution map. Analysis of the high nugget effect
      ratio indicates high, small-scale variations that are consistent with potential
      emissions from an adjacent electrolytic manganese plant.

PMID- 24122142
TI  - Disposal of dredged sediments in tropical soils: ecotoxicological  effects on
      earthworms.
AB  - The upper limit concentrations of metals established by international
      legislations for dredged sediment disposal and soil quality do not take into
      consideration the properties of tropical soils (generally submitted to more
      intense weathering processes) on metal availability and ecotoxicity. Aiming to
      perform an evaluation on the suitability of these threshold values in tropical
      regions, the ecotoxicity of metal-contaminated dredged sediment from the
      Guanabara Bay (Rio de Janeiro, Brazil) was investigated. Acute and avoidance
      tests with Eisenia andrei were performed with mixtures of dredged sediment with a
      ferralsol (0.00, 6.66, 13.12, 19.98, and 33.30 %) and a chernosol (0.00, 6.58,
      13.16, 19.74, and 32.90 %). Mercury, lead, nickel, chromium, copper, and zinc
      concentrations were measured in test mixtures and in tissues of surviving
      earthworms from the acute tests. While ferralsol test mixtures provoked
      significant earthworm avoidance response at concentrations >=13.31 %, the
      chernosol mixtures showed significant avoidance behavior only at the 19.74 %
      concentration. The acute tests showed higher toxicity in ferralsol mixtures (LC50
      = 9.9 %) compared to chernosol mixtures (LC50 = 16.5 %), and biomass increased at
      the lowest sediment doses in treatments of both test soils. Most probably, the
      expansive clay minerals present in chernosol contributed to reduce metal
      availability in chernosol mixtures, and consequently, the ecotoxicity of these
      treatments. The bioconcentration factors (BCF) for zinc and copper were lower
      with increasing concentrations of the dredged sediment, indicating the existence
      of internal regulating processes. Although the BCF for mercury also decreased
      with the increasing test concentrations, the known no biological function of this
      metal in the earthworms metabolism lead to suppose that Hg measured was not
      present in bioaccumulable forms. BCFs estimated for the other metals were
      generally higher in the highest dredged sediment doses.

PMID- 24122143
TI  - A candidate gene association study for growth performance in an improved giant
      freshwater prawn (Macrobrachium rosenbergii ) culture line.
AB  - A candidate gene approach using type I single nucleotide polymorphism (SNP)
      markers can provide an effective method for detecting genes and gene regions that
      underlie phenotypic variation in adaptively significant traits. In the absence of
      available genomic data resources, transcriptomes were recently generated in
      Macrobrachium rosenbergii to identify candidate genes and markers potentially
      associated with growth. The characterisation of 47 candidate loci by ABI re
      sequencing of four cultured and eight wild samples revealed 342 putative SNPs.
      Among these, 28 SNPs were selected in 23 growth-related candidate genes to
      genotype in 200 animals selected for improved growth performance in an
      experimental GFP culture line in Vietnam. The associations between SNP markers
      and individual growth performance were then examined. For additive and dominant
      effects, a total of three exonic SNPs in glycogen phosphorylase (additive), heat
      shock protein 90 (additive and dominant) and peroxidasin (additive), and a total
      of six intronic SNPs in ankyrin repeats-like protein (additive and dominant),
      rolling pebbles (dominant), transforming growth factor-beta induced precursor
      (dominant), and UTP-glucose-1-phosphate uridylyltransferase 2 (dominant) genes
      showed significant associations with the estimated breeding values in the
      experimental animals (P =0.001-0.031). Individually, they explained 2.6-4.8 % of
      the genetic variance (R2=0.026-0.048). This is the first large set of SNP markers
      reported for M. rosenbergii and will be useful for confirmation of associations
      in other samples or culture lines as well as having applications in marker
      assisted selection in future breeding programs.

PMID- 24122144
TI  - Short-term potentiation of membrane resealing in neighboring  cells is mediated
      by purinergic signaling.
AB  - Resealing of a disrupted plasma membrane in the micron-size range requires Ca(2+)
      regulated exocytosis. When cells are wounded twice, the second membrane
      disruption reseals more quickly than the initial wound. This response is protein
      kinase C (PKC)-dependent and protein kinase A dependent in the early stages. In
      the long term (24 h), potentiation of membrane resealing in a wounded cell
      depends on gene expression mediated by a transcription factor, cyclic adenosine
      monophosphate response element binding protein(CREB), which is activated by a PKC
      dependent and p38 mitogen-activated protein kinase-dependent pathway. In
      addition,a recent study demonstrated that wounding of Madin-Darby canine kidney
      (MDCK) cells potentiates membrane resealing in neighboring cells by activating
      CREB-dependent gene expression through nitric oxide (NO) signaling. The present
      study demonstrated that wounding of MDCK cells induces short-term potentiation of
      membrane resealing in neighboring cells in addition to a long-term response.
      Inhibition of purinergic signaling suppressed short-term potentiation of membrane
      resealing in neighboring cells, but not long-term potentiation. By contrast,
      inhibition of NO signaling did not suppress the short-term response in
      neighboring cells. These results suggest that cell membrane disruption stimulates
      at least two intercellular signaling pathways, NO and purinergic signaling, to
      potentiate cell membrane resealing in neighboring cells.

PMID- 24122145
TI  - Prevalence of different forms of infarct-atypical late gadolinium enhancement in
      patients early and late after heart transplantation.
AB  - BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR)
      enables high-resolution myocardial tissue characterization, showing the results
      of different injuries, especially in the early period after heart transplantation
      (HTX). OBJECTIVES: We sought to apply LGE-CMR to investigate the prevalence and
      patterns of infarct-atypical myocardial involvement and associated mechanisms in
      patients early and late after HTX. METHODS: LGE-CMR was performed on a 1.5-T MRI
      scanner (Philips, Best, the Netherlands) in 89 patients: group 1 (48 patients)
      less than 2.5 years after operation (1.2 +/- 0.5 years) and group 2 (41 patients)
      later this period (8.2 +/- 4.2 years). Following LGE-CMR, the presence,
      distribution, patterns of infarct-atypical LGE and possible associated mechanisms
      were assessed. RESULTS: 71 % of group 1 patients (34/48) showed infarctatypical
      LGE whereas 57 % of group 2 patients (22/41) were affected (p = 0.25). Fewer
      segments/patients were involved later after HTX (1.6 +/- 2.0 vs. 2.9 +/- 3.1
      segments/ patient; p = 0.03), but only diffuse LGE-CMR pattern decreased
      significantly (11.5 % of affected segments in group 1 vs. 6.5 % in group 2;
      p?0.001). Group 2 had lower ischemic time (181 +/- 53 vs. 208 +/- 61 min; p =
      0.03), the donors were younger (33 +/- 13 vs. 41 +/- 13 years; p = 0.01) and
      fewer donors were Toxoplasma gondii seropositive (4 vs. 22pts; p?0.001).
      CONCLUSION: Infarct-atypical LGE was found in a significant number of patients
      early post-HTX, however, fewer patients and myocardial segments per patient were
      affected later after HTX. Many potential factors seem to be involved, but the
      exact mechanisms are still unclear. Future studies are necessary to test
      prognostic implications associated with LGE-CMR patterns.

PMID- 24122147
TI  - Economic threshold for Tetranychus urticae (Acari: Tetranychidae) in clementine
      mandarins Citrus clementina.
AB  - Tetranychus urticae is a key pest of citrus in Spain, especially of clementine
      mandarin trees. The effects of this mite on fruit production were assessed in 24
      clementine trees for three consecutive years. Trees were visited weekly and
      spider mite and phytoseiid mite populations and leaf flush patterns were
      estimated. At the end of the season, mandarins were harvested, weighed, and mite
      damage (scarring on the fruit) characterized. Negative relationships between
      spider mite density and yield (kg/tree) and fruit damage (% scarred fruit rind)
      were found. The multivariate regressions highlighted the key role of phytoseiid
      mites and leaf flush patterns, which were negatively related to fruit damage. The
      shortest sampling period that satisfactorily predicted fruit damage at harvest,
      extended from August to mid-October. For IPM purposes, an action threshold of
      31.1 mites m-2 of symptomatic leaf was estimated. Taking into account spider mite
      dynamics, the economic threshold ranged from 10 to 15 mites m-2 of symptomatic
      leaf. When this threshold is exceeded growers would have a 1-week window to apply
      the control technologies against T. urticae of their choice.

PMID- 24122148
TI  - Suicide ideation and associated mortality in adult survivors of childhood cancer.
AB  - BACKGROUND: Adult survivors of childhood cancer are at risk for suicide ideation,
      although longitudinal patterns and rates of recurrent suicide ideation are
      unknown. This study investigated the prevalence of late report (ie, after initial
      assessment) and recurrent suicide ideation in adult survivors of childhood
      cancer, identified predictors of suicide ideation, and examined associations
      among suicide ideation and mortality. METHODS: Participants included 9128 adult
      survivors of childhood cancer and 3082 sibling controls enrolled in the Childhood
      Cancer Survivor Study who completed a survey question assessing suicide ideation
      on one or more occasions between 1994 and 2010. Suicide ideation was assessed
      using the Brief Symptom Inventory-18 instrument. Mortality data was ascertained
      from the National Death Index. RESULTS: Survivors were more likely to report late
      (odds ratio [OR] =1.9, 95% confidence interval [CI] =1.5-2.5) and recurrent
      suicide ideation (OR=2.6, 95% CI=1.8-3.8) compared to siblings. Poor physical
      health status was associated with increased risk of suicide ideation in survivors
      (late report: OR=1.9, 95% CI=1.3-2.7; recurrent: OR=1.9, 95% CI=1.2-2.9). Suicide
      ideation was associated with increased risk for all-cause mortality (hazard
      ratio=1.3, 95% CI=1.03-1.6) and death by external causes (hazard ratio=2.4, 95%
      CI=1.4-4.1). CONCLUSIONS: Adult survivors of childhood cancer are at risk for
      late-report and recurrent suicide ideation, which is associated with increased
      risk of mortality. Routine screening for psychological distress in adult
      survivors appears warranted, especially for survivors who develop chronic
      physical health conditions.

PMID- 24122149
TI  - Longitudinal decline of lower extremity muscle power in healthy and mobility
      limited older adults: influence of muscle mass, strength, composition,
      neuromuscular activation and single fiber contractile properties.
AB  - PURPOSE: This longitudinal study examined the major physiological mechanisms that
      determine the age-related loss of lower extremity muscle power in two distinct
      groups of older humans. We hypothesized that after ~3 years of follow-up,
      mobility-limited older adults (mean age: 77.2 +/- 4, n = 22, 12 females) would
      have significantly greater reductions in leg extensor muscle power compared to
      healthy older adults (74.1 +/- 4, n = 26, 12 females). METHODS: Mid-thigh muscle
      size and composition were assessed using computed tomography. Neuromuscular
      activation was quantified using surface electromyography and vastus lateralis
      single muscle fibers were studied to evaluate intrinsic muscle contractile
      properties. RESULTS: At follow-up, the overall magnitude of muscle power loss was
      similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P >
      0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P
      < 0.01) and strength (-5.9 %, P < 0.02), however, these parameters were preserved
      in healthy older (P >= 0.7). Neuromuscular activation declined significantly
      within healthy older, but not in mobility-limited participants. Within both
      groups, the cross-sectional areas of type I and IIA muscle fibers were preserved
      while substantial increases in single fiber peak force (>30 %), peak power (>200
      %) and unloaded shortening velocity (>50 %) were elicited at follow-up.
      CONCLUSION: Different physiological mechanisms contribute to the loss of lower
      extremity muscle power in healthy older and mobility-limited older adults.
      Neuromuscular changes may be the critical early determinant of muscle power
      deficits with aging. In response to major whole muscle decrements, major
      compensatory mechanisms occur within the contractile properties of surviving
      single muscle fibers in an attempt to restore overall muscle power and function
      with advancing age.

PMID- 24122150
TI  - Food allergy and quality of life: what have we learned?
AB  - Health-related quality of life (HRQL) has become an emerging focus of interest in
      food allergy. Food allergy is a disease characterized by low mortality and
      symptoms which only occur during an allergic reaction. However, food-allergic
      patients continuously need to be alert when eating in order to prevent
      potentially severe allergic reactions, which may be fatal. Fear of such reactions
      and the need to be continuously vigilant may seriously compromise their HRQL.
      During the last decade, numerous studies have been published on food allergy and
      HRQL. The development of reliable, valid and responsive instruments for measuring
      HRQL in food allergic patients has facilitated this research even further. Such
      instruments have given insight into the specific problems a patient may face and
      the impact of food allergy-related interventions from the patient's perspective.
      This paper focuses on the most significant findings regarding this topic since
      its first appearance in the literature in 2000.

PMID- 24122151
TI  - An investigation of ecological correlates with hand and foot morphology in
      callitrichid primates.
AB  - Studies of primate taxonomy and phylogeny often depend on comparisons of limb
      dimensions, yet there is little information on how morphology correlates and
      contributes to foraging strategies and ecology. Callitrichid primates are ideal
      for comparative studies as they exhibit a range of body size, limb proportions
      and diet. Many callitrichid species exhibit a high degree of exudativory, and to
      efficiently exploit these resources, they are assumed to have evolved
      morphologies that reflect a level of dependence on these resources. We tested
      assumptions by considering measurements of limb proportion and frictional
      features of the volar surfaces in preserved specimens of 25 species with relation
      to published life history and ecological data. The degree of exudativory and
      utilization of vertical substrates during foraging were found to correlate both
      with size and with size-corrected foot and hand dimensions. Smaller species,
      which engage in greater degrees of exudativory, had proportionally longer hands
      and feet and more curved claw-like tegulae (nails) on their digits to facilitate
      climbing on vertical substrates. The density of patterned ridges (dermatoglyphs)
      on the volar surfaces of the hands and feet is higher in more exudativorous
      genera, suggesting a role in climbing on vertical tree trunks during foraging.
      Dermatoglyph comparisons suggest that ridges on the soles and palms may
      facilitate food procurement by enhancing frictional grip during exudate feeding.
      Volar pad features corroborate taxonomic relationships described from dental
      morphology.

PMID- 24122152
TI  - Network.assisted analysis to prioritize GWAS results: principles,  methods and
      perspectives.
AB  - Genome-wide association studies (GWAS) have rapidly become a powerful tool in
      genetic studies of complex diseases and traits. Traditionally, single marker
      based tests have been used prevalently in GWAS and have uncovered tens of
      thousands of disease-associated SNPs. Network-assisted analysis (NAA) of GWAS
      data is an emerging area in which network-related approaches are developed and
      utilized to perform advanced analyses of GWAS data in order to study various
      human diseases or traits. Progress has been made in both methodology development
      and applications of NAA in GWAS data, and it has already been demonstrated that
      NAA results may enhance our interpretation and prioritization of candidate genes
      and markers. Inspired by the strong interest in and high demand for advanced GWAS
      data analysis, in this review article, we discuss the methodologies and
      strategies that have been reported for the NAA of GWAS data. Many NAA approaches
      search for subnetworks and assess the combined effects of multiple genes
      participating in the resultant subnetworks through a gene set analysis. With no
      restriction to pre-defined canonical pathways, NAA has the advantage of defining
      subnetworks with the guidance of the GWAS data under investigation. In addition,
      some NAA methods prioritize genes from GWAS data based on their interconnections
      in the reference network. Here, we summarize NAA applications to various diseases
      and discuss the available options and potential caveats related to their
      practical usage. Additionally, we provide perspectives regarding this rapidly
      growing research area.

PMID- 24122153
TI  - Anti-necroptosis chemical necrostatin-1 can also suppress apoptotic and
      autophagic pathway to exert neuroprotective effect in mice intracerebral
      hemorrhage model.
AB  - Necroptosis was recently discovered as one form of programmed cell death (PCD)
      and could be specifically inhibited by necrostatin-1. The aim of this study was
      to examine the effect of necrostatin-1 on brain injury and investigate the role
      of necrostatin-1 on the other two types PCD (apoptosis and autophagic cell death)
      in a mouse intracerebral hemorrhage (ICH) model. Male ICR mice received an
      infusion of type IV collagenase to induce ICH or saline as control into the left
      striatum. In the presence of vehicle, 3-MA, zVAD, and necrostatin-1 were
      pretreated with a single intracerebroventricular (i.c.v.) injection in the
      ipsilateral ventricle 15 min before ICH, respectively. Compared with vehicle
      groups, necrostatin-1 treatment significantly reduced injury volume and propidium
      iodide-positive cells at 24 and 72 h after ICH. Immunoblotting analysis showed
      that necrostatin-1 treatment suppressed autophagic-associated proteins (LC3-II,
      Beclin-1) and maintained p62 at normal level at 24 and 72 h after ICH. In
      addition, necrostatin-1 treatment enhanced the protein level of Bcl-2 and
      decreased the protein level of cleaved caspase-3 and the Beclin-1/Bcl-2 ratio at
      24 and 72 h after ICH. Moreover, both 3-MA and necrostatin-1 treatment could
      suppress cleaved caspase-3 and LC3-II production, whereas zVAD treatment could
      inhibit caspase-3 cleavage but increased LC3-II protein levels at 72 h after ICH.
      Taken together, the data demonstrated for the first time that the specific
      inhibitor necrostatin-1 suppressed apoptosis and autophagy to exert these
      neuroprotective effects after ICH and that there existed a cross-talk among
      necroptosis, apoptosis, and autophagy after ICH.

PMID- 24122154
TI  - Discussions and decisions of the 2012-2014 International Committee on Taxonomy of
      Viruses (ICTV) Filoviridae Study Group, January 2012-June 2013.
AB  - The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group
      prepares proposals on the classification and nomenclature of filoviruses to
      reflect current knowledge or to correct disagreements with the International Code
      of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus
      taxonomy has been corrected and updated, but parts of it remain controversial,
      and several topics remain to be debated. This article summarizes the decisions
      and discussion of the currently acting ICTV Filoviridae Study Group since its
      inauguration in January 2012.

PMID- 24122155
TI  - The complete genome sequences of two isolates of potato black  ringspot virus and
      their relationship to other isolates  and nepoviruses.
AB  - The complete nucleotide sequences of RNA 1 and RNA 2 of the nepovirus potato
      black ringspot virus (PBRSV) from two different isolates were determined, as well
      as partial sequences from two additional isolates. RNA1 is 7,579-7,598
      nucleotides long and contains one single open reading frame (ORF), which is
      translated into a large polyprotein with 2,325 amino acids and a molecular weight
      of 257 kDa. The complete sequence of RNA2 ranges from 3857 to 3918 nt between the
      different isolates. It encodes a polyprotein of 1079-1082 amino acids with a
      molecular weight of 120 kDa. Sequence comparison using the Pro-Pol region and CP
      showed that all four isolates formed two distinct groups, corresponding to potato
      and arracacha, that were closely related to each other and also to tobacco
      ringspot virus (TRSV). Comparing our data to those obtained with other
      nepoviruses, our results confirm that PBRSV belongs to a distinct species and is
      a member of subgroup A in the genus Nepovirus based on its RNA2 size, genome
      organization, and nucleotide sequence.

PMID- 24122156
TI  - Early event detection using a home monitoring system for patients with cardiac
      pacemakers.
AB  - AIM: To analyze the clinical applications and observe the priority of Home
      Monitoring (HM) systems for early event detection including clinical cardiac
      warning events, abnormal device parameters and other events in patients with
      permanent cardiac pacemakers. METHODS: A total of 58 patients who received dual
      chamber pacemakers, ICDs and CRT-P/Ds were enrolled and monitored using the HM
      system for 416 +/- 398 days. Automatic system-transmitted events by HM and
      related clinical information were recorded and consulted by well-trained
      physicians. Conventional and unconventional follow-up initialed by HM results
      were analyzed. RESULTS: Forty patients (69 %) transmitted abnormal events via the
      HM system. Twenty-one of these were cardiac events. Atrial fibrillation (AF) was
      the most common transmitted clinical event. AF was detected an average of 44.26
      +/- 18.33 days earlier in HM patients than on routine clinical visits alone. A
      total of 20 patients reported 62 events related to abnormal device parameters.
      Among these events, disabled ACC/ATM function was the most common warning event
      (17 times) transmitted by 14 of the patients, and they were detected an average
      of 67.6 +/- 29.0 days ahead of the routine office device follow-up. A total of
      seven patients reported silent events and totally eight patients were required to
      make an unscheduled clinical visit. Eighteen patients (31 %) transmitted no
      warning event and accepted no parameter adjustment during observation.
      CONCLUSIONS: The HM system is useful in early detection of abnormal warning
      events as well as the primary detection of silent events in post-pacemaker
      implantation patients. Additionally, the HM system benefits patients during the
      whole process of device follow-up by real-time monitoring, and reduces medical
      costs effectively for patients with no abnormal reports or necessity of parameter
      adjustment.

PMID- 24122157
TI  - Dissipation and residue of triforine in strawberry and soil.
AB  - Two independent field trials were performed in Guangdong and Hubei, China in 2011
      to investigate the dissipation and residue levels of triforine in strawberry and
      soil. A fast and simple method using gas chromatography with electron capture
      detector was developed and validated to determine triforine levels in strawberry
      and soil. The average recovery of triforine in strawberry ranged from 87.46 to
      104.32 % with a relative standard deviation (RSD) of 0.72 to 4.54 %; that in soil
      ranged from 83.82 to 103.01 % with an RSD of 3.89 to 4.36 %. The limit of
      quantification of the proposed method was 0.01 mg/kg for both strawberry and
      soil. The results suggest that the triforine dissipation curves followed the
      first-order kinetic. The half-lives of triforine in strawberry from Guangdong and
      Hubei were 3.58 and 4.42 days, respectively; those in soil were 3.53 and 4.10
      days, respectively. The terminal residues of triforine in strawberry ranged from
      0.032 to 0.264 mg/kg at preharvest intervals of 0.5, 1, and 3 days. These values
      are lower than the maximum residue limit of 1 mg/kg in strawberry set by the
      Codex Alimentarius Commission.

PMID- 24122158
TI  - Different hydrodynamic processes regulated on water quality  (nutrients,
      dissolved oxygen, and phytoplankton biomass)  in three contrasting waters of Hong
      Kong.
AB  - The subtropical Hong Kong (HK) waters are located at the eastern side of the
      Pearl River Estuary. Monthly changes of water quality, including nutrients,
      dissolved oxygen (DO), and phytoplankton biomass (Chl-a) were routinely
      investigated in 2003 by the Hong Kong Environmental Protection Department in
      three contrasting waters of HK with different prevailing hydrodynamic processes.
      The western, eastern, and southern waters were mainly dominated by nutrient
      replete Pearl River discharge, the nutrient-poor coastal/shelf oceanic waters,
      and mixtures of estuarine and coastal seawater and sewage effluent of Hong Kong,
      respectively. Acting in response, the water quality in these three contrasting
      areas showed apparently spatial-temporal variation pattern. Nutrients usually
      decreased along western waters to eastern waters. In the dry season, the water
      column was strongly mixed by monsoon winds and tidal currents, which resulted in
      relatively low Chl-a (<5 MUg l(-1)) and high bottom DO (>4 mg l(-1)), suggesting
      that mixing enhanced the buffering capacity of eutrophication in HK waters.
      However, in the wet season, surface Chl-a was generally >10 MUg l(-1) in southern
      waters in summer due to halocline and thermohaline stratification, adequate
      nutrients, and light availability. Although summer hypoxia (DO <2 mg l(-1)) was
      episodically observed near sewage effluent site and in southern waters induced by
      vertical stratification, the eutrophication impacts in HK waters were not as
      severe as expected owing to P limitation and short water residence time in the
      wet season.

PMID- 24122159
TI  - Human health risk assessment of lead from mining activities at semi-arid
      locations in the context of total lead exposure.
AB  - Lead from historical mining and mineral processing activities may pose potential
      human health risks if materials with high concentrations of bioavailable lead
      minerals are released to the environment. Since the Joint Expert Committee on
      Food Additives of Food and Agriculture Organization/World Health Organization
      withdrew the Provisional Tolerable Weekly Intake of lead in 2011, an alternative
      method was required for lead exposure assessment. This study evaluated the
      potential lead hazard to young children (0-7 years) from a historical mining
      location at a semi-arid area using the U.S. EPA Integrated Exposure Uptake
      Biokinetic (IEUBK) Model, with selected site-specific input data. This study
      assessed lead exposure via the inhalation pathway for children living in a
      location affected by lead mining activities and with specific reference to semi
      arid conditions and made comparison with the ingestion pathway by using the
      physiologically based extraction test for gastro-intestinal simulation.
      Sensitivity analysis for major IEUBK input parameters was conducted. Three groups
      of input parameters were classified according to the results of predicted blood
      concentrations. The modelled lead absorption attributed to the inhalation route
      was lower than 2 % (mean +/- SE, 0.9 % +/- 0.1 %) of all lead intake routes and
      was demonstrated as a less significant exposure pathway to children's blood,
      compared with ingestion. Whilst dermal exposure was negligible, diet and
      ingestion of soil and dust were the dominant parameters in terms of children's
      blood lead prediction. The exposure assessment identified the changing role of
      dietary intake when house lead loadings varied. Recommendations were also made to
      conduct comprehensive site-specific human health risk assessment in future
      studies of lead exposure under a semi-arid climate.

PMID- 24122160
TI  - 42nd Congress of the "Groupe Francais des Pesticides" (French Group of Pesticide
      research--GFP 2012) ENSIP, Poitiers, France, 30 May-1 June 2012.
AB  - The 42nd congress of the "Groupe Francais des Pesticides" (French Group of
      Pesticide research--GFP 2012) took place 30 May-1 June at the "Ecole Nationale
      Superieure d'Ingenieurs de Poitiers" (ENSIP), a French generalist engineering
      grande ecole in Poitiers. Its focus is on the protection of the environment and
      is part of the University of Poitiers, one of the oldest universities in Europe.
      GFP is an annual conference where the latest developments in the field of
      pesticide research are presented. The topics most commonly discussed mainly
      concern environmental quality, monitoring, fate, and transfer of pesticides in
      the environment or risks associated with use of pesticides, but every year a key
      theme sets the tone. For this 42nd edition, the theme "Innovative strategies for
      plant protection" was retained.

PMID- 24122161
TI  - Toxicity of urban highway runoff in Shanghai to Zebrafish (Danio rerio ) embryos
      and luminous bacteria (Vibrio qinghaiensis.Q67).
AB  - Pollution from urban highway runoff has been identified as one of the major
      causes of the deterioration of receiving water quality. The purpose of this study
      is to assess the toxicity of urban storm water samples in Shanghai using the
      zebrafish (Danio rerio ) embryo test and the bacterial luminescence (Vibrio
      qinghaiensis ) assay. The toxicity of highway runoff from seventeen storm events
      was investigated in both grab and composite samples. Zebrafish embryos were
      exposed to the runoff samples and development parameters including lethality,
      spontaneous movements in 20 s, heart beat rate, hatching rate, and abnormality of
      zebrafish embryos were observed after 24, 48, 72, and 96 h of exposure.
      Inhibition rates of luminescence intensity were also recorded. The results showed
      that in the zebrafish embryo toxicity tests, both grab and composite samples
      increased the lethality, reduced the percentage with spontaneous movements and
      heart beats, inhibited the hatching of embryos, and induced morphological
      abnormalities. In the Vibrio qinghaiensis toxicity test, all the grab samples
      inhibited the luminescence, while some of the composite samples promoted it,
      which indicated that different types of toxicants might have been affecting the
      species. The multivariate statistics analysis indicated that heavy metal (zinc,
      manganese, and copper) and PAHs might mainly contribute to the toxicity of runoff
      samples.

PMID- 24122162
TI  - Ionic composition of wet precipitation over the southern slope of central
      Himalayas, Nepal.
AB  - Severe atmospheric pollution transported to Himalayas from South Asia may affect
      fragile ecosystem and can be harmful for human health in the region. In order to
      understand the atmospheric chemistry in the southern slope of central Himalayas,
      where the data is limited, precipitation has been sampled at four sites:
      Kathmandu (1,314 m), Dhunche (2, 065 m), Dimsa (3,078 m), and Gosainkunda (4,417
      m) in Nepal for over a 1-year period characterized by an urban, rural, and remote
      sites, respectively. HCO3 - is the dominant anion, while the NH4 + is the
      dominant cation in precipitation at the four sites. Generally, most of ions
      (e.g., SO4 2-, NO3 -, NH4 +, HCO3 -, and Ca2+) have higher concentrations in
      urban site compared to the rural sites. Neutralization factor calculation showed
      that precipitation in the region is highly neutralized by NH4 + and Ca2+.
      Empirical orthogonal function and correlation analysis indicated that the
      precipitation chemistry was mostly influenced by crustal, anthropogenic, and
      marine sources in Nepal. Among different sites, urban area was mostly influenced
      by anthropogenic inputs and crustal dusts, whereas remote sites were mostly from
      marine and crustal sources. Seasonal variations show higher ionic concentrations
      during non-monsoon seasons mainly due to limited precipitation amount. On the
      other hand, lower ionic concentrations were observed during monsoon season when
      higher amount of precipitation washes out aerosols. Thus, precipitation chemistry
      from this work can provide a useful database to evaluate atmospheric environment
      and its impacts on ecosystem in the southern slope of central Himalayas, Nepal.

PMID- 24122163
TI  - Decontamination of a municipal landfill leachate from endocrine disruptors using
      a combined sorption/bioremoval approach.
AB  - Sorption and biodegradation are the main mechanisms for the removal of endocrine
      disruptor compounds (EDs) from both solid and liquid matrices. There are recent
      evidences about the capacity of white-rot fungi to decontaminate water systems
      from phenolic EDs by means of their ligninolytic enzymes. Most of the available
      studies report the removal of EDs by biodegradation or adsorption separately.
      This study assessed the simultaneous removal of five EDs-the xenoestrogens
      bisphenol A (BPA), ethynilestradiol (EE2), and 4-n-nonylphenol (NP), and the
      herbicide linuron and the insecticide dimethoate-from a municipal landfill
      leachate (MLL) using a combined sorption/bioremoval approach. The adsorption
      matrices used were potato dextrose agar alone or added with each of the following
      adsorbent materials: ground almond shells, a coffee compost, a coconut fiber, and
      a river sediment. These matrices were either not inoculated or inoculated with
      the fungus Pleurotus ostreatus and superimposed on the MLL. The residual amount
      of each ED in the MLL was quantified after 4, 7, 12, and 20 days by HPLC analysis
      and UV detection. Preliminary experiments showed that (1) all EDs did not degrade
      significantly in the untreatedMLL for at least 28 days, (2) the mycelial growth
      of P. ostreatus was largely stimulated by components of the MLL, and (3) the
      enrichment of potato dextrose agar with any adsorbent material favored the fungal
      growth for 8 days after inoculation. A prompt relevant disappearance of EDs in
      the MLL occurred both without and, especially, with fungal activity, with the
      only exception of the very water soluble dimethoate that was poorly adsorbed and
      possibly degraded only during the first few days of experiments. An almost
      complete removal of phenolic EDs, especially EE2 and NP, occurred after 20 days
      or much earlier and was generally enhanced by the adsorbent materials used. Data
      obtained indicated that both adsorption and biodegradation mechanisms contribute
      significantly to MLL decontamination from the EDs studied and that the efficacy
      of the methodology adopted is directly related to the hydrophobicity of the
      contaminant.

PMID- 24122164
TI  - TXRF analysis of soils and sediments to assess environmental contamination.
AB  - Total reflection x-ray fluorescence spectroscopy (TXRF) is proposed for the
      elemental chemical analysis of crustal environmental samples, such as sediments
      and soils. A comparative study of TXRF with respect to flame atomic absorption
      spectroscopy and inductively coupled plasma optical emission spectroscopy was
      performed. Microwave acid digestion and suspension preparation methods are
      evaluated. A good agreement was found among the results obtained with different
      spectroscopic techniques and sample preparation methods for Cr, Mn, Fe, Ni, Cu,
      and Zn. We demonstrated that TXRF is suitable for the assessment of environmental
      contamination phenomena, even if the errors for Pb, As, V, and Ba are ingent.

PMID- 24122165
TI  - Sorption of cyromazine on humic acid: Effects of pH, ionic strength and foreign
      ions.
AB  - Cyromazine (CY) is a triazine pesticide used as an insect growth inhibitor for
      fly control in cattle manure, field crops, vegetables, and fruits. Sorption of CY
      onto humic acid (HA) may affect its environmental fate. In this study, HA was
      used to investigate the sorption of CY at different solution chemistry conditions
      (pH, ionic strength) and in the presence of foreign ions and norfloxacin. All
      sorption isotherms fitted well with the Freundlich and Langmuir models. The
      sorption reached a maximum at initial pH 4.0 over the initial pH range of 3.0
      7.0, implying that the primary sorption mechanism was cation exchange interaction
      between CY+ species and the negatively charged functional groups of HA.
      Increasing Ca2+ concentration resulted in a considerable reduction in the Kd
      values of CY, hinting that Ca2+ had probably competed with CY+ for the cation
      exchange sites on the surfaces of HA. The sorption of CY on HA in different ionic
      media followed the order of NH4Cl ~ KCl > K2SO4 > ZnCl2 ~ CaCl2 at pH 5.0.
      Spectroscopic evidence demonstrated that the amino groups and triazine ring of CY
      was responsible for sorption onto HA, while the carboxyl group and the O-alkyl
      structure of HA participated in adsorbing CY.

PMID- 24122166
TI  - Hypoxia simultaneously alters satellite cell-mediated angiogenesis and hepatocyte
      growth factor expression.
AB  - Skeletal muscle regeneration is a multifaceted process requiring the spatial and
      temporal coordination of myogenesis as well as angiogenesis. Hepatocyte growth
      factor (HGF) plays a pivotal role in myogenesis by activating satellite cells
      (SC) in regenerating muscle and likely plays a role as a contributor to
      revascularization. Moreover, repair of a functional blood supply is critical to
      ameliorate tissue ischemia and restore skeletal muscle function, however effects
      of hypoxia on satellite cell-mediated angiogenesis remain unclear. The objective
      of this study was to examine the role of HGF and effect of hypoxia on the
      capacity of satellite cells to promote angiogenesis. To characterize the role of
      HGF, a microvascular fragment (MVF) culture model coupled with satellite cell
      conditioned media (CM) was employed. The activity of HGF was specifically blocked
      in SC CM reducing sprout length compared to control CM. In contrast, MVF sprout
      number did not differ between control or HGF-deficient SC CM media. Next, we
      cultured MVF in the presence of CM from satellite cells exposed to normoxic (20%
      O2 ) or hypoxic (1% O2 ) conditions. Hypoxic CM recapitulated a MVF angiogenic
      response identical to HGF deficient satellite cell CM. Hypoxic conditions
      increased satellite cell HIF-1alpha protein abundance and VEGF mRNA abundance but
      decreased HGF mRNA abundance compared to normoxic satellite cells. Consistent
      with reduced HGF gene expression, HGF promoter activity decreased during hypoxia.
      Taken together, this data indicates that hypoxic modulation of satellite cell
      mediated angiogenesis involves a reduction in satellite cell HGF expression.

PMID- 24122167
TI  - Correlation of inhibitory effects of polymers on indomethacin precipitation in
      solution and amorphous solid crystallization based on molecular interaction.
AB  - PURPOSE: To correlate the polymer's degree of precipitation inhibition of
      indomethacin in solution to the amorphous stabilization in solid state. METHODS:
      Precipitation of indomethacin (IMC) in presence of polymers was continuously
      monitored by a UV spectrophotometer. Precipitates were characterized by PXRD, IR
      and SEM. Solid dispersions with different polymer to drug ratios were prepared
      using solvent evaporation. Crystallization of the solid dispersion was monitored
      using PXRD. Modulated differential scanning calorimetry (MDSC), IR, Raman and
      solid state NMR were used to explore the possible interactions between IMC and
      polymers. RESULTS: PVP K90, HPMC and Eudragit E100 showed precipitation
      inhibitory effects in solution whereas Eudragit L100, Eudragit S100 and PEG 8000
      showed no effect on IMC precipitation. The rank order of precipitation inhibitory
      effect on IMC was found to be PVP K90 > Eudragit E100 > HPMC. In the solid state,
      polymers showing precipitation inhibitory effect also exhibited amorphous
      stabilization of IMC with the same rank order of effectiveness. IR, Raman and
      solid state NMR studies showed that rank order of crystallization inhibition
      correlates with strength of molecular interaction between IMC and polymers.
      CONCLUSIONS: Correlation is observed in the polymers ability to inhibit
      precipitation in solution and amorphous stabilization in the solid state for IMC
      and can be explained by the strength of drug polymer interactions.

PMID- 24122169
TI  - Is Neoseiulus wearnei the Neoseiulus californicus of Australia?
AB  - Species of the family Phytoseiidae are known as predatory mites, some of them
      being used in crops to control mite pests, all around the world. Neoseiulus
      (=Cydnodromus) californicus is among the most commonly used Phytoseiidae species
      in biological control programs, especially in vineyards, orchards and vegetable
      fields. This species is distributed world-wide but has never been reported from
      Australia. On the other hand, specimens morphologically close to N. californicus
      have been assigned to a species called Neoseiulus wearnei, only reported from
      Australia. Investigations based on morphological and molecular comparisons were
      carried out to investigate whether these two taxa are conspecific. Morphological
      analyses showed no significant difference between specimens identified as N.
      wearnei and N. californicus. Similarly, genetic distances between these taxa were
      null, showing that all these specimens belong to the same species. Although it is
      not yet possible to conclude that all the specimens identified as N. wearnei are
      N. californicus, we can conclude that N. californicus is present in Australia.
      The information about the biology of N. californicus can thus now be applied to
      the Australian population of this species for biological control purposes.

PMID- 24122171
TI  - ?
AB  - Sarcoidosis is an idiopathic systemic disease, which is characterized by the
      presence of non-caseating granulomas in the affected organs. Cutaneous
      manifestations are frequently the first clue to the diagnosis; however, the
      clinical picture of the lesions is heterogenous. Here we report on a 66-year-old
      woman with localized indurations of the skin on both forearms that were diagnosed
      as a rare morphea-like skin involvement of a systemic sarcoidosis.

PMID- 24122170
TI  - Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of
      their activity.
AB  - TRPA1, one of the transient receptor potential channels, has been reported to be
      involved in nociception and inflammatory pain, suggesting that this molecule
      could be a promising target for the development of analgesic agents. We screened
      several monoterpene analogs of camphor, which is known to inhibit human (h)
      TRPA1, to identify more effective naturally occurring TRPA1 antagonists. Borneol,
      2-methylisoborneol, and fenchyl alcohol exhibited higher inhibitory effects on
      hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed further
      that the S873, T874, and Y812 residues of hTRPA1 were involved in the inhibitory
      effects, suggesting that the hydroxyl group in the six-membered ring of the
      inhibitors may be interacting with these amino acids. Further research on these
      identified TRPA1 antagonists could lead to new pain therapeutics.

PMID- 24122172
TI  - An investigation of the challenges in reconstructing PET images of a freely
      moving animal.
AB  - Imaging the brain of a freely moving small animal using positron emission
      tomography (PET) while simultaneously observing its behaviour is an important
      goal for neuroscience. While we have successfully demonstrated the use of line-of
      response (LOR) rebinning to correct the head motion of confined animals, a large
      proportion of events may need to be discarded because they either 'miss' the
      detector array after transformation or fall out of the acceptance range of a
      sinogram. The proportion of events that would have been measured had motion not
      occurred, so-called 'lost events', is expected to be even larger for freely
      moving animals. Moreover, the data acquisition in the case of a freely moving
      animal is further complicated by a complex attenuation field. The aims of this
      study were (a) to characterise the severity of the 'lostevents' problem for the
      freely moving animal scenario, and(b) to investigate the relative impact of
      attenuation correction errors on quantitative accuracy of reconstructed images. A
      phantom study was performed to simulate the uncorrelated motion of a target and
      non-target sourcevolume. A small animal PET scanner was used to acquirelist-mode
      data for different sets of phantom positions. The list-mode data were processed
      using the standard LOR rebinning approach, and multiple frame variants of this
      designed to reduce discarded events. We found that LOR rebinning caused up to 86
      % 'lost events', and artifacts that we attribute to incomplete projections, when
      applied to a freely moving target. This fraction was reduced by up to 18 % using
      the variant approaches, resulting in slightly reduced image artifacts. The effect
      of the non-target compartment on attenuation correction of the target volume was
      surprisingly small. However, for certain poses where the target and non-target
      volumes are aligned transaxially in the field-of-view, the attenuation problem
      becomes more complex and sophisticated correction methods will be required. We
      conclude that there are limitations with the LOR rebinning approach and
      simplified attenuation correction for freely moving animals requiring the
      development and validation of more sophisticated approaches.

PMID- 24122174
TI  - Health promotion in Swedish schools: school managers' views.
AB  - Schools are recognized worldwide as settings for health promotion, and leadership
      has a bearing on schools' ability to be health promoting. School managers have a
      great influence on what is prioritized in school, which in turn affects students'
      school performance and health. There is lack of research into school managers'
      views on health promotion, and what they consider to be central to health
      promotion. The aim was therefore to examine school managers' views about what
      health promotion in schools include. An explorative design, qualitative content
      analysis, was performed. In-depth interviews were conducted with all 13 school
      managers of a middle-sized municipality in central Sweden. The analysis had both
      manifest and latent content and three categories: 'Organization and
      Collaboration', 'Optimize the arena' and 'Strengthen the individual', and 10
      subcategories emerged. The theme, 'Opportunities for learning and a good life',
      describes the latent content of these categories. Taking into account the views
      of school managers are important because these views help form a more complete
      picture of how school managers work with health promotion and what is needed to
      enhance health promotion to improve students' opportunities for learning and a
      good life. The Ottawa Charter for Health promotion is thereby transformed into
      practice.

PMID- 24122173
TI  - Second nonocular tumors among survivors of retinoblastoma treated with
      contemporary photon and proton radiotherapy.
AB  - BACKGROUND: The leading cause of death among patients with hereditary
      retinoblastoma is second malignancy. Despite its high rate of efficacy,
      radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor.
      Proton RT allows for significant sparing of nontarget tissue. The current study
      compared the risk of second malignancy in patients with retinoblastoma who were
      treated with photon and proton RT. METHODS: A retrospective review was performed
      of patients with retinoblastoma who were treated with proton RT at the
      Massachusetts General Hospital or photon RT at Boston Children's Hospital between
      1986 and 2011. RESULTS: A total of 86 patients were identified, 55 of whom
      received proton RT and 31 of whom received photon RT. Patients were followed for
      a median of 6.9 years (range, 1.0 years-24.4 years) in the proton cohort and 13.1
      years (range, 1.4 years-23.9 years) in the photon cohort. The 10-year cumulative
      incidence of RT-induced or in-field second malignancies was significantly
      different between radiation modalities (proton vs photon: 0% vs 14%; P = .015).
      The 10-year cumulative incidence of all second malignancies was also different,
      although with borderline significance (5% vs 14%; P = .120). CONCLUSIONS:
      Retinoblastoma is highly responsive to radiation. The central objection to the
      use of RT, the risk of second malignancy, is based on studies of patients treated
      with antiquated, relatively nonconformal techniques. The current study is, to the
      authors' knowledge, the first to present a series of patients treated with the
      most conformal of the currently available external-beam RT modalities. Although
      longer follow-up is necessary, the preliminary data from the current study
      suggest that proton RT significantly lowers the risk of RT-induced malignancy.

PMID- 24122175
TI  - Effect of zinc on nectar secretion of Hibiscus rosa -sinensis L.
AB  - Zinc toxicity in secretory cells caused a range of effects, mainly depending on
      metal concentration. Low concentrations activated nectary function increasing
      nectar secretion but secretion was greatly inhibited or stopped entirely by
      ongoing concentration. Water loss rate of zinc treated flower parts was
      significantly reduced whereas green sepals were dehydrated more rapidly in
      comparison to colored petals. The content of zinc, calcium, magnesium and
      manganese increased mainly in sepals under excess of zinc, but in the secreted
      nectar this metal was not evident. Morphological changes were observed in
      mucilage cells concerning the mucilage structure and appearance. The
      parenchymatic, subglandular cells displayed an early vacuolarization and
      cytoplasm condensation. Secretory hairs appeared to be thinner, the apical cell
      folded inwards and plasmolytic shrinkage became severe in all cells. The waxy
      cuticula showed an increased electron density. A plasmalemma detachment from the
      external cell walls was observed creating a gap between cell wall and
      plasmalemma. ER cisterns of all treated nectary hairs dominated the cytoplasm and
      electron dense deposits were seen within its profiles. A great number of other
      organelles were also present, showing electron dense deposits in their membranes
      as well. The vacuome was drastically reduced in all cells, except in the
      subglandular ones and electron dense membrane remnants were observed.

PMID- 24122176
TI  - The influence of acetaminophen on repeated sprint cycling performance.
AB  - INTRODUCTION: The aim of this study was to investigate the effect of
      acetaminophen on repeated sprint cycling performance. METHODS: Nine
      recreationally active male participants completed a graded exercise test, a
      familiarisation set of Wingate Anaerobic Tests (WAnTs) and two experimental sets
      of WAnTs (8 * 30 s sprints, 2 min active rest intervals). In the experimental
      WAnTs, participants ingested either 1.5 g acetaminophen or a placebo in a double
      blind, randomised, crossover design. During the WAnT trials, participants
      provided ratings of perceived pain 20 s into each sprint. Mean and peak power
      output and heart rate were recorded immediately following each sprint, and
      percentage decrement in mean power output was subsequently calculated. RESULTS:
      Participants cycled at a significantly greater mean power output over the course
      of 8 WAnTs (p < 0.05) following the ingestion of acetaminophen (391 +/- 74 vs.
      372 +/- 90 W), due to a significantly greater mean power output during sprints 6,
      7 and 8 (p < 0.05). Percentage decrements in mean power output were also
      significantly reduced (p < 0.05) following acetaminophen ingestion (17 +/- 14 vs.
      24 +/- 17 %). No significant differences in peak power output, perceived pain or
      heart rate were observed between conditions. CONCLUSION: Acetaminophen may have
      improved performance through the reduction of pain for a given work rate, thereby
      enabling participants to exercise closer to a true physiological limit. These
      results suggest that exercise may be regulated by pain perception, and that an
      increased pain tolerance can improve exercise performance.

PMID- 24122177
TI  - Diffuse migratory connectivity in two species of shrubland birds: evidence from
      stable isotopes.
AB  - Connecting seasonal ranges of migratory birds is important for understanding the
      annual template of stressors that influence their populations. Brewer's sparrows
      (Spizella breweri) and sagebrush sparrows (Artemisiospiza nevadensis) share
      similar sagebrush (Artemisia spp.) habitats for breeding but have different
      population trends that might be related to winter location. To link breeding and
      winter ranges, we created isoscapes of deuterium [stable isotope ratio (delta) of
      deuterium; delta2H] and nitrogen (delta15N) for each species modeled from isotope
      ratios measured in feathers of 264 Brewer's and 82 sagebrush sparrows and
      environmental characteristics at capture locations across their breeding range.
      We then used feather 2Hf and 15Nf measured in 1,029 Brewer's and 527 sagebrush
      sparrows captured on winter locations in southwestern United States to assign
      probable breeding ranges. Intraspecies population mixing from across the breeding
      range was strong for both Brewer's and sagebrush sparrows on winter ranges.
      Brewer's sparrows but not sagebrush sparrows were linked to more northerly
      breeding locations in the eastern part of their winter range. Winter location was
      not related to breeding population trends estimated from US Geological Survey
      Breeding Bird Survey routes for either Brewer's or sagebrush sparrows. Primary
      drivers of population dynamics are likely independent for each species; Brewer's
      and sagebrush sparrows captured at the same winter location did not share
      predicted breeding locations or population trends. The diffuse migratory
      connectivity displayed by Brewer's and sagebrush sparrows measured at the coarse
      spatial resolution in our analysis also suggests that local environments rather
      than broad regional characteristics are primary drivers of annual population
      trends.

PMID- 24122178
TI  - Avoidance of intraguild predation leads to a long-term positive trait-mediated
      indirect effect in an insect community.
AB  - Intraguild predation among natural enemies is common in food webs with insect
      herbivores at their base. Though intraguild predation may be reciprocal,
      typically one species suffers more than the other and frequently exhibits
      behavioural strategies to lessen these effects. How such short-term behaviours
      influence population dynamics over several generations has been little studied.
      We worked with a model insect community consisting of two species of aphid
      feeding on different host plants (Acyrthosiphon pisum on Vicia and Sitobion
      avenae on Triticum), a parasitoid (Aphidius ervi) that attacks both species, and
      a dominant intraguild predator (Coccinella septempunctata) that also feeds on
      both aphids (whether parasitized or not). As reported previously, we found A.
      ervi avoided chemical traces of C. septempunctata. In population cages in the
      laboratory, application of C. septempunctata extracts to Vicia plants reduced
      parasitism on A. pisum. This did not increase parasitism on the other aphid
      species, our predicted short-term trait-mediated effect. However, a longer term
      multigenerational consequence of intraguild predator avoidance was observed. In
      cages where extracts were applied in the first generation of the study,
      parasitoid recruitment was reduced leading to higher population densities of both
      aphid species. S. avenae thus benefits from the presence of a dominant intraguild
      predator foraging on another species of aphid (A. pisum) on a different food
      plant, a long-term, trait-mediated example of apparent mutualism. The mechanism
      underlying this effect is hypothesized to be the reduced searching efficiency of
      a shared parasitoid in the presence of cues associated with the dominant
      predator.

PMID- 24122179
TI  - Roles of the volatile terpene, 1,8-cineole, in plant-herbivore interactions: a
      foraging odor cue as well as a toxin?
AB  - Olfaction is an important sense for many animals, yet its role in foraging by
      herbivores is poorly known. Many plants contain volatile compounds, such as
      terpenes, that are not only volatile but can be toxic if ingested. Volatile
      terpenes can be used by herbivores to assess leaf quality, but there is little
      evidence for whether they are also used as a searching cue. We applied the giving
      up density (GUD) framework to examine fine-scale foraging by two free-ranging
      mammalian herbivores, the brush-tail possum (Trichosurus vulpecula) and the swamp
      wallaby (Wallabia bicolor), using patches with food and an inedible matrix that
      varied in content of a volatile terpene, 1,8-cineole. We tested the effect of (1)
      increasing dietary cineole concentration, and (2) masking the food odor by adding
      cineole to the inedible matrix, thus overriding the smell released by the diet.
      In both species GUD was affected by dietary cineole; a high cineole concentration
      raised GUD, consistent with its role as a toxin. There was a significant effect
      of masking on GUD for wallabies but not for possums, suggesting that odor was an
      important foraging cue at the feeding patch only for the former. Differences in
      ecological niche and diet may explain this pattern. We suggest that herbivores,
      such as the swamp wallaby, opportunistically eavesdrop on plant volatiles, i.e.,
      take advantage of the signal proffered for a different function. The cost of this
      eavesdropping for plants, however, is presumably counteracted by other ecological
      benefits of these volatiles, including a reduction in leaf consumption as a
      function of toxicity.

PMID- 24122180
TI  - 2013 classification criteria for systemic sclerosis: an American College of
      Rheumatology/European League against Rheumatism collaborative initiative.
AB  - OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification
      criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited
      cutaneous SSc. The present work, by a joint committee of the ACR and the European
      League Against Rheumatism (EULAR), was undertaken for the purpose of developing
      new classification criteria for SSc. METHODS: Using consensus methods, 23
      candidate items were arranged in a multicriteria additive point system with a
      threshold to classify cases as SSc. The classification system was reduced by
      clustering items and simplifying weights. The system was tested by 1) determining
      specificity and sensitivity in SSc cases and controls with scleroderma-like
      disorders, and 2) validating against the combined view of a group of experts on a
      set of cases with or without SSc. RESULTS: It was determined that skin thickening
      of the fingers extending proximal to the metacarpophalangeal joints is sufficient
      for the patient to be classified as having SSc; if that is not present, 7
      additive items apply, with varying weights for each: skin thickening of the
      fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries,
      interstitial lung disease or pulmonary arterial hypertension, Raynaud's
      phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the
      validation sample were, respectively, 0.91 and 0.92 for the new classification
      criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected
      cases were classified in accordance with consensus-based expert opinion. All
      cases classified as SSc according to the 1980 ACR criteria were classified as SSc
      with the new criteria, and several additional cases were now considered to be
      SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better
      than the 1980 ACR criteria for SSc and should allow for more patients to be
      classified correctly as having the disease.

PMID- 24122181
TI  - Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: To determine whether oral quinacrine increases survival in sporadic
      Creutzfeldt-Jakob disease (sCJD). METHODS: This NIH/National Institute on Aging
      funded, double-blinded, placebo-controlled, stratified randomization treatment
      trial was conducted at the University of California, San Francisco from February
      2005 through May 2009 (ClinicalTrials.gov, NCT00183092). Subjects were randomized
      (50:50) to quinacrine (300 mg daily) or placebo with inpatient evaluations at
      baseline, and planned for months 2, 6, and 12. Subjects returning for their month
      2 visit were offered open-label quinacrine. The primary outcome was survival from
      randomization to month 2. RESULTS: Of 425 patients referred, 69 subjects
      enrolled, 54 subjects were randomized to active drug or placebo, and 51 subjects
      with sCJD were included in survival analyses. Survival for the randomized portion
      of the trial (first 2 months) showed no significant difference between the 2
      groups (log-rank statistic, p = 0.43; Cox proportional relative hazard = 1.43,
      quinacrine compared with placebo, 95% confidence interval = 0.58, 3.53). The
      quinacrine-treated group, however, declined less on 2 of 3 functional scales, the
      modified Rankin and Clinical Dementia Rating, than the placebo group during the
      first 2 months. CONCLUSION: This interventional study provides Class I evidence
      that oral quinacrine at 300 mg per day does not improve 2-month survival of
      patients with sCJD, compared with placebo. Importantly, this study shows that
      double-blinded, placebo-controlled, randomized treatment trials are possible in
      prion disease. Furthermore, the quantitative data collected on the course of sCJD
      will be useful for future trials. CLASSIFICATION OF EVIDENCE: This study provides
      Class I evidence that quinacrine does not improve survival for people with sCJD
      when given orally at a dose of 300 mg per day for 2 months.

PMID- 24122182
TI  - IV thrombolysis and renal function.
AB  - OBJECTIVE: To investigate the association of renal impairment on functional
      outcome and complications in stroke patients treated with IV thrombolysis (IVT).
      METHODS: In this observational study, we compared the estimated glomerular
      filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3
      6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria
      of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted
      odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients
      without IVT treatment served as a comparison group. RESULTS: Among 4,780 IVT
      treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m(2)). A GFR
      decrease by 10 mL/min/1.73 m(2) increased the risk of poor outcome (OR [95% CI]):
      (ORunadjusted 1.20 [1.17-1.24]; ORadjusted 1.05 [1.01-1.09]), death (ORunadjusted
      1.33 [1.28-1.38]; ORadjusted 1.18 [1.11-1.249]), and sICH (ORunadjusted 1.15
      [1.01-1.22]; ORadjusted 1.11 [1.04-1.20]). Low GFR was independently associated
      with poor 3-month outcome (ORadjusted 1.32 [1.10-1.58]), death (ORadjusted 1.73
      [1.39-2.14]), and sICH (ORadjusted 1.64 [1.21-2.23]) compared with normal GFR (60
      120 mL/min/1.73 m(2)). Low GFR (ORadjusted 1.64 [1.21-2.23]) and stroke severity
      (ORadjusted 1.05 [1.03-1.07]) independently determined sICH. Compared with
      patients who did not receive IVT, treatment with IVT in patients with low GFR was
      associated with poor outcome (ORadjusted 1.79 [1.41-2.25]), and with favorable
      outcome in those with normal GFR (ORadjusted 0.77 [0.63-0.94]). CONCLUSION: Renal
      function significantly modified outcome and complication rates in IVT-treated
      stroke patients. Lower GFR might be a better risk indicator for sICH than age. A
      decrease of GFR by 10 mL/min/1.73 m(2) seems to have a similar impact on the risk
      of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke
      severity.

PMID- 24122183
TI  - Myocardial scintigraphy may predict the conversion to probable dementia with Lewy
      bodies.
AB  - OBJECTIVE: To compare the usefulness of brain perfusion SPECT and (123)I
      metaiodobenzylguanidine ((123)I-MIBG) in predicting the conversion of possible
      dementia with Lewy bodies (DLB) to probable DLB. METHODS: We examined 94 patients
      with possible DLB based on the Consensus Criteria for the Clinical Diagnosis of
      DLB by N-Isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) brain perfusion SPECT
      and (123)I-MIBG myocardial scintigraphy. After 1 year of follow-up, 33 of 94
      patients met the criteria for probable DLB. (123)I-IMP brain perfusion SPECT and
      (123)I-MIBG myocardial scintigraphy were tested as predictors of the conversion
      from possible DLB to probable DLB. A receiver operating characteristic (ROC)
      analysis was performed. RESULTS: The areas under the ROC curves for SPECT for
      predicting the conversion to probable DLB from possible DLB based on the
      occipital/cerebellum and occipital/striatum cortex ratios of blood flow counts
      were 0.591 and 0.585, respectively. The areas under the ROC curves for (123)I
      MIBG based on the early heart to mediastinum (H/M) ratio, delayed H/M ratio, and
      washout rate were 0.935, 0.936, and 0.884, respectively. CONCLUSION: (123)I-MIBG
      myocardial scintigraphy is a good predictor of the future conversion of possible
      DLB to probable DLB.

PMID- 24122184
TI  - Improving diagnosis of possible DLB: is there a role for MIBG myocardial
      scintigraphy?

PMID- 24122185
TI  - Gray matter damage predicts the accumulation of disability 13 years later in MS.
AB  - OBJECTIVES: To assess the value of conventional and magnetization transfer (MT)
      MRI measures of white matter (WM) and gray matter (GM) damage, and their 12-month
      change, in predicting long-term disability and cognitive impairment in multiple
      sclerosis (MS). METHODS: Conventional and MT MRI brain scans were obtained at
      baseline and at 12 months in 73 patients, who were followed prospectively with
      clinical visits and rating of the Expanded Disability Status Scale score and the
      MS severity score (MSSS) for a median period of 13.3 years. At 13-year follow-up,
      a neuropsychological assessment was also performed when possible. T2-hyperintense
      and T1-hypointense lesion volumes, GM fraction (GMF), WM fraction, thalamic
      fraction, average lesion MT ratio (MTR), average GM MTR, average normal-appearing
      WM MTR, and thalamic MTR were measured. Random forest and multivariable analyses
      were performed to identify the predictors of neurologic deterioration and
      cognitive impairment at 13 years. RESULTS: At 13-year follow-up, 66% of patients
      showed significant worsening of disability and 37% had worsened cognitively. The
      multivariable model, in which Expanded Disability Status Scale deterioration at
      final follow-up was the dependent variable, identified baseline GMF (odds ratio
      [OR] = 0.79, p = 0.01) as the only predictor of worsening of disability (C-index
      = 0.69). Baseline disease duration (OR = 1.50, p = 0.08) and average GM MTR (OR =
      0.87, p = 0.03) were independent variables associated with cognitive
      deterioration (C-index = 0.97). Baseline MSSS (beta = 0.50, p < 0.0001) and
      baseline GMF (beta = -0.32, p = 0.0005) predicted MSSS at follow-up (r(2) =
      0.45). CONCLUSIONS: GM damage is one of the key factors associated with long-term
      accumulation of disability and cognitive impairment in MS.

PMID- 24122187
TI  - Cardiac function and oxygen saturation during maximal breath-holding in air and
      during whole-body surface immersion.
AB  - INTRODUCTION: The magnitude of the oxygen-sparing effect induced by the diving
      response in humans is still under debate. We wished to compare cardiovascular
      changes during maximal breath-holding (BH) in air and during whole-body immersion
      at the surface in a group of BH divers. METHODS: Twenty-one divers performed a
      maximal static apnea in air or during whole-body immersion.
      Dopplerechocardiography, arterial blood pressure and haemoglobin saturation
      (SaO2) were obtained at the beginning of, and at 1/3, 2/3 and maximal BH time.
      RESULTS: BH time was on the average 3.6 +/- 0.4 min, with no differences between
      the two conditions. SaO2 significantly decreased during BH in both conditions,
      but was significantly higher during immersion as compared to the dry (P = 0.04).
      In both conditions, BH induced a significant linear increase in right ventricular
      diameter (P < 0.001), left ventricular (LV) volumes (P < 0.001) and LV stroke
      volume (P < 0.001) but a significant linear decrease in LV ejection fraction (P =
      0.033). In both conditions, Doppler diastolic parameters showed changes
      suggesting a constrictive/restrictive left ventricular filling pattern (i.e., an
      increase of early diastolic left ventricular filling velocity, P = 0.005, and a
      decrease in the deceleration time of early diastolic left ventricular filling. P
      < 0.001). CONCLUSION: BH induces progressive LV enlargement both in air and whole
      body immersion, associated with reduced LV ejection fraction and progressive
      hindrance to diastolic filling. For a similar apnea duration, SaO2 decreased less
      during immersed BH, indicating an O2-sparing effect of diving, suggesting that
      interruption of apnea was not triggered by a threshold critical value of blood O2
      desaturation.

PMID- 24122186
TI  - Nutri-epigenetics ameliorates blood-brain barrier damage and neurodegeneration in
      hyperhomocysteinemia: role of folic acid.
AB  - Epigenetic mechanisms underlying nutrition (nutrition epigenetics) are important
      in understanding human health. Nutritional supplements, for example folic acid, a
      cofactor in one-carbon metabolism, regulate epigenetic alterations and may play
      an important role in the maintenance of neuronal integrity. Folic acid also
      ameliorates hyperhomocysteinemia, which is a consequence of elevated levels of
      homocysteine. Hyperhomocysteinemia induces oxidative stress that may
      epigenetically mediate cerebrovascular remodeling and leads to neurodegeneration;
      however, the mechanisms behind such alterations remain unclear. Therefore, the
      present study was designed to observe the protective effects of folic acid
      against hyperhomocysteinemia-induced epigenetic and molecular alterations leading
      to neurotoxic cascades. To test this hypothesis, we employed 8-weeks-old male
      wild-type (WT) cystathionine-beta-synthase heterozygote knockout methionine-fed
      (CBS+/- + Met), WT, and CBS+/- + Met mice supplemented with folic acid (FA) [WT +
      FA and CBS+/- + Met + FA, respectively, 0.0057-MUg g-1 day-1 dose in drinking
      water/4 weeks]. Hyperhomocysteinemia in CBS+/- + Met mouse brain was accompanied
      by a decrease in methylenetetrahydrofolate reductase and an increase in S
      adenosylhomocysteine hydrolase expression, symptoms of oxidative stress,
      upregulation of DNA methyltransferases, rise in matrix metalloproteinases, a drop
      in the tissue inhibitors of metalloproteinases, decreased expression of tight
      junction proteins, increased permeability of the blood-brain barrier,
      neurodegeneration, and synaptotoxicity. Supplementation of folic acid to CBS+/- +
      Met mouse brain led to a decrease in the homocysteine level and rescued
      pathogenic and epigenetic alterations, showing its protective efficacy against
      homocysteine-induced neurotoxicity.

PMID- 24122188
TI  - Functional comparison between critical flicker fusion frequency and simple
      cognitive tests in subjects breathing air or oxygen in normobaria.
AB  - INTRODUCTION: Measurement of inert gas narcosis and its degree is difficult
      during operational circumstances, hence the need for a reliable, reproducible and
      adaptable tool. Although being an indirect measure of brain function, if
      reliable, critical flicker fusion frequency (CFFF) could address this need and be
      used for longitudinal studies on cortical arousal in humans. METHODS: To test the
      reliability of this method, the comparison between CFFF and three tests (Math
      Processing Task, Trail-Making Task, and Perceptual Vigilance Task) from the
      Psychology Experiment Building Language battery (PEBL) were used to evaluate the
      effect of 10 minutes of 100% normobaric oxygen breathing on mental performance in
      20 healthy male volunteers. RESULTS: Breathing normobaric oxygen significantly
      improved all but one of the measured parameters, with an increase of CFFF (117.3
      +/- 10.04% of baseline, P < 0.0001) and a significant reduction of time to
      complete in both the math-processing (2,103 +/- 432.1 ms to 1,879 +/- 417.5 ms, P
      = 0.0091) and trail-making tasks (1,992 +/- 715.3 to 1,524 +/- 527.8 ms, P =
      0.0241). The magnitude of CFFF change and time to completion of both tests were
      inversely correlated (Pearson r = -0.9695 and -0.8731 respectively, P < 0.0001).
      The perceptual vigilance task did not show a difference between air and O2 (P >
      0.4). CONCLUSIONS: The CFFF test provides an assessment of cognitive function
      that is similar to some tests from PEBL, but requires a less complicated set up
      and could be used under various environmental conditions including diving.
      Further research is needed to assess the combined effects of increased pressure
      and variations in inspired gas mixtures during diving.

PMID- 24122189
TI  - A prospective analysis of independent patient risk factors for middle ear
      barotrauma in a multiplace hyperbaric chamber.
AB  - INTRODUCTION: Middle ear barotrauma (MEBT) is the most common complication of
      hyperbaric oxygen therapy (HBOT). We wished to determine whether independent risk
      factors could predict which patients will require tympanostomy tubes in order to
      continue HBOT. METHODS: Data regarding demographics, medical history and physical
      examination were collected prospectively over one year. Multivariate logistic
      regression was used to analyse the data. RESULTS: One hundred and six patients
      were included. The cumulative risk of MEBT over the first five treatments was
      35.8% and that for needing tympanostomy tubes was 10.3%, while that for needing
      tubes at any time was 13.2%. Risk factors for MEBT on bivariate analysis were
      older age, history of ENT radiation and anticoagulant use. Risk factors for
      requiring tympanostomy tubes included a history of cardiovascular disease and
      patients being treated for an infective condition. The adjusted multivariate
      logistic model identified history of difficulty equalising as the only
      characteristic significantly associated with MEBT during the first five
      treatments, adjusted odds ratio (AOR) (95%CI): 11.0 (1.1 - 111.7). Being female,
      AOR (95%CI): 24.7 (1.8 - 339.7), and having a history of cardiovascular disease,
      AOR (95%CI): 20.7 (2.0 - 215.3), were significantly associated with the need for
      tympanostomy tubes during the first five HBOT, but there was no significant
      association between any other characteristics and the need for tubes at any
      point. CONCLUSION: Despite some significant risk factors for MEBT being
      identified, we were unable to predict accurately enough which patients needed
      tympanostomy tubes during their HBOT to recommend these being placed
      prophylactically in selected patients.

PMID- 24122190
TI  - Effects of diving and oxygen on autonomic nervous system and cerebral blood flow.
AB  - Recreational scuba diving is a popular leisure activity with the number of divers
      reaching several millions worldwide. Scuba diving represents a huge challenge for
      integrative physiology. In mammalian evolution, physiological reflexes developed
      to deal with lack of oxygen, rather than with an excess, which makes adaptations
      to scuba diving more difficult to describe and understand than those associated
      with breath-hold diving. The underwater environment significantly limits the use
      of equipment to register the organism's functions, so, in most instances,
      scientific theories are built on experiments that model real diving to some
      extent, like hyperbaric exposures, dive reflexes or water immersion. The aim of
      this review is to summarise the current knowledge related to the influence
      exerted by physiological conditions specific to diving on the autonomic nervous
      system and cerebral blood flow. The main factors regulating cerebral blood flow
      during scuba diving are discussed as follows: 1) increased oxygen partial
      pressure; 2) immersion-related trigemino-cardiac reflexes and 3) exposure to
      cold, exercise and stress. Also discussed are the potential mechanisms associated
      with immersion pulmonary oedema. 

PMID- 24122191
TI  - Characterization of early thermal burns and the effects of hyperbaric oxygen
      treatment: a pilot study.
AB  - BACKGROUND AND AIMS: Studies investigating hyperbaric oxygen treatment (HBOT) to
      improve outcome in burns have been inconclusive. In this study, we aimed to
      characterize early thermal burns injury in adult patients with < 40% total body
      surface area (TBSA) and to determine the effects of HBOT administered within 24 h
      to 48 h of a burn injury. METHODS: Seventeen subjects were randomized into
      control (n = 9) and HBOT treatment (n = 8) arms. Burn depth, measured by laser
      Doppler imaging (LDI) and histologically, white blood cell (WBC) count and plasma
      cytokine inflammatory markers were assessed at 24 h (pre HBOT) and 48 h (post
      HBOT) post burn, as were immunohistochemistry and microbiology of burns tissue
      samples at 48 h post burn. RESULTS: WBC count and serum interleukin (IL)-1beta,
      IL-4, IL-6, IL-10 and interferon-gamma were significantly elevated 24 h after
      burn, but no significant changes in any of these parameters were found with HBOT.
      HBOT had no significant effect on burn depth. Two HBOT patients and four control
      patients developed positive bacterial cultures. CONCLUSIONS: Slower than
      anticipated recruitment resulted in considerably fewer patients than planned
      being studied. Inflammatory markers were significantly increased at 24 h in
      patients with < 40% TBSA burn. Early HBOT had no apparent effects on any of the
      parameters measured in this small pilot study. HBOT may possibly have a broad
      spectrum antimicrobial effect worthy of further study. We report our methodology
      in detail as a possible model for future burns studies.

PMID- 24122192
TI  - Pulmonary oedema in breath-hold diving: an unusual presentation and computed
      tomography findings.
AB  - Haemoptysis and pulmonary oedema following deep breath-hold diving have been
      described in recent years. We describe the case of a 33-year-old healthy military
      diver who presented symptoms suggestive of pulmonary oedema after two breathhold
      dives, the first lasting 0.5-1 min and the second 1-2 min, to 6 metres' depth in
      the sea. The diagnosis was promptly confirmed with chest computed tomography
      showing bilateral interstitial infiltrates in the upper regions of the lungs. To
      our knowledge, this is the first report to document pulmonary oedema in this
      setting of shallow breath-hold diving with atypical radiological presentation. A
      definite mechanism for this specific distribution of lung injury remains unclear.

PMID- 24122193
TI  - Efficacy of hyperbaric oxygen therapy in a young woman with idiopathic branch
      retinal artery occlusion.
AB  - We present a case of branch retinal artery occlusion (BRAO) in a healthy 20-year
      old woman with no history of ocular or systemic diseases or drug use. She
      presented with a sudden decrease in visual acuity associated with a visual field
      defect of the right eye, which she had first noticed 4 hours earlier. Examination
      showed a BRAO with oedema at the upper part of the macula and surrounding area,
      and confirmed on fluorescein angiography. The left eye was normal. She was sent
      immediately for hyperbaric oxygen therapy (HBOT) and received 10 sessions (over
      20 days) of 2 hours each at a pressure of 253 kPa. Follow up at four months
      showed a normal fundus, and visual acuity of 20/25. Visual field and fundoscopy
      were normal. Investigations for a cause of the BRAO proved negative. Retinal
      artery occlusion is rare in young people, and early application of HBOT in
      patients with RAO appears to improve outcome. 

PMID- 24122194
TI  - Hyperbaric oxygen in the treatment of perichondritis of the pinna.
AB  - Perichondritis is a condition characterized by pain, swelling and purulent
      discharge from the external ear, which may progress to a deformity of the pinna.
      The presence of co-morbidities such as diabetes mellitus may aggravate the
      situation. The main aetiological agent is Pseudomonas aeruginosa and treatment
      consists of antibiotics combined with surgical drainage of the ear. We present
      the case of a diabetic patient with recurrent perichondritis of the pinna treated
      with hyperbaric oxygen therapy, with successful healing. Hyperbaric oxygen
      therapy has proved beneficial as adjunctive therapy of lesions in diabetic
      patients with foot ulcers, acting in the regeneration of intracellular free
      radicals and promotion of wound-healing factors. Thus, owing to its mechanisms of
      action, its effect on other injuries such as perichondritis in diabetic patients
      may be beneficial and lead to improvement. 

PMID- 24122196
TI  - Effect of ginger- and garlic-supplemented diet on growth performance, some
      hematological parameters and immune responses in juvenile Huso huso.
AB  - Physiological parameters and growth performance of Huso huso fingerlings fed with
      diet supplemented with herbal plants were studied in this study. Dietary
      treatments were 0 g (= control), 1.0 g (garlic) and 1.0 g (ginger) of 100 g(-1)
      feed for 60 days. Specific growth rate, body weight gain and condition factor
      were significantly increased in ginger treatment at the end of the trial. Highest
      levels of erythrocyte and hematocrit were observed in fingerlings ginger group
      after 60 days. Globulin increased significantly in ginger group, and the highest
      level of albumin was observed in garlic group. To sum up, it seems that herbal
      diet can improve some growth and physiological parameters in this species.

PMID- 24122195
TI  - Cerebral microbleeds and macrobleeds: should they influence our recommendations
      for antithrombotic therapies?
AB  - Intracerebral hemorrhage (ICH, or macrobleeds) and cerebral microbleeds-smaller
      foci of hemosiderin deposits commonly detected by magnetic resonance imaging of
      older adults with or without ICH-are both associated with an increased risk of
      future ICH. These hemorrhagic pathologies also share risk factors with ischemic
      thromboembolic conditions that may require antithrombotic therapy, requiring
      specialists in cardiology, internal medicine, and neurology to weigh the benefits
      vs hemorrhagic risks of antithrombotics in individual patients. This paper will
      review recent advances in our understanding of hemorrhage prone cerebrovascular
      pathologies with a particular emphasis on use of these markers in decision making
      for antithrombotic use. 

PMID- 24122197
TI  - Partial characterisation of digestive proteases of the Mayan  cichlid Cichlasoma
      urophthalmus.
AB  - The characterisation of digestive proteases in native freshwater fish such as the
      Mayan cichlid Cichlasoma urophthalmus provides scientific elements that may be
      used to design balanced feed that matches with the digestive capacity of the
      fish. The purpose of this study was to characterise the digestive proteases,
      including the effect of the pH and the temperature on enzyme activity and
      stability, as well as the effect of inhibitors using multienzymatic extracts of
      the stomach and intestine of C. urophthalmus juveniles. Results showed that the
      optimum activities of the acid and alkaline proteases occurred at pH values of 3
      and 9, respectively, whereas their optimum temperatures were 55 and 65  degrees
      C, respectively. The acid proteases were most stable at pH values of 2-3 and at
      temperatures of 35-45  degrees C, whereas the alkaline proteases were most stable
      at pH values of 6-9 and at 25-55  degrees C. The inhibition assays recorded a
      residual activity of 4% with pepstatin A for the acid proteases. The inhibition
      of the alkaline proteases was greater than 80% with TPCK, TLCK, EDTA and
      ovalbumin, and of 60 and 43.8% with PMSF and SBT1, respectively. The results
      obtained in this study make it possible to state that C. urophthalmus has a
      sufficiently complete digestive enzyme machinery to degrade food items
      characteristic of an omnivorous fish species, although specimens showed a
      tendency to carnivory.

PMID- 24122199
TI  - Taking a broad view: understanding and treating conduct problems in youth.

PMID- 24122200
TI  - Predictive genetic testing in children: constitutional mismatch repair deficiency
      cancer predisposing syndrome.
AB  - Biallelic germline mutations in mismatch repair genes predispose to
      constitutional mismatch repair deficiency syndrome (CMMR-D). The condition is
      characterized by a broad spectrum of early-onset tumors, including hematological,
      brain and bowel and is frequently associated with features of Neurofibromatosis
      type 1. Few definitive screening recommendations have been suggested and no
      published reports have described predictive testing. We report on the first case
      of predictive testing for CMMR-D following the identification of two non
      consanguineous parents, with the same heterozygous mutation in MLH1: c.1528C > T.
      The genetic counseling offered to the family, for their two at-risk daughters, is
      discussed with a focus on the ethical considerations of testing children for
      known cancer-causing variants. The challenges that are encountered when reporting
      on heterozygosity in a child younger than 18 years (disclosure of carrier status
      and risk for Lynch syndrome), when discovered during testing for homozygosity,
      are addressed. In addition, the identification of CMMR-D in a three year old, and
      the recommended clinical surveillance that was proposed for this individual is
      discussed. Despite predictive testing and presymptomatic screening, the sudden
      death of the child with CMMR-D syndrome occurred 6 months after her last
      surveillance MRI. This report further highlights the difficulty of developing
      guidelines, as a result of the rarity of cases and diversity of presentation.

PMID- 24122201
TI  - Association of CTLA4 gene polymorphism (rs5742909) with cervical cancer: a meta
      analysis.
AB  - Previous studies suggested that CTLA4 polymorphism (rs5742909) is associated with
      susceptibility to cervical cancer. In the present study, we performed a meta
      analysis to systematically summarize the possible association between rs5742909
      and the risk for cervical cancer. We conducted a search of case-control studies
      on the associations of rs5742909 with susceptibility to cervical cancer in
      PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled
      Trials, Wanfang database in China, and Chinese National Knowledge Infrastructure
      databases. We extracted the data from eligible studies for meta-analysis. The
      association of cervical cancer risk with rs5742909 was estimated by pooled odds
      ratios (ORs) and 95 % confidence intervals (95 % CIs). There were four studies on
      rs5742909 and cervical cancer in our meta-analysis. Our results suggested that
      both T allele frequency (OR = 1.63, 95 % CI 1.06-2.50; P = 0.03) and (TT + CT)
      genotype distribution (OR = 1.72, 95 % CI 1.07-2.77; P = 0.03) of the rs5742909
      were associated with risk for cervical cancer. This meta-analysis suggests that
      rs5742909 is associated with the risk of cervical cancer. Well-designed studies
      with larger sample size and more ethnic groups are required to further validate
      the results.

PMID- 24122202
TI  - Effects of murine double minute 2 polymorphisms on the risk and survival of
      osteosarcoma: a systemic review and meta-analysis.
AB  - Murine double minute 2 (MDM2) plays an important role in the carcinogenesis of
      many cancers including osteosarcoma. We performed a systemic review and meta
      analysis to assess the effects of MDM2 polymorphisms on osteosarcoma risk and
      survival of patients with osteosarcoma. PubMed, Web of Science, and Wanfang
      databases were searched for eligible studies on the associations of MDM2
      polymorphisms with osteosarcoma risk and survival of patients with osteosarcoma.
      Pooled odds ratio (OR) or hazard ratio (HR) with 95 % confidence intervals (95 %
      CIs) was used to assess the effects of MDM2 polymorphisms on osteosarcoma risk
      and survival of patients with osteosarcoma. Overall, MDM2 rs2279744 polymorphism
      was associated with a risk of osteosarcoma (allele model, OR = 1.60, 95 % CI 1.23
      2.07, P < 0.001; codominant model, OR = 2.47, 95 % CI 1.46-4.19, P = 0.001;
      recessive model, OR = 2.13, 95 % CI 1.32-3.46, P = 0.002; dominant model, OR =
      1.61, 95 % CI 1.12-2.33, P = 0.01). MDM2 rs1690916 polymorphism was also
      associated with a risk of osteosarcoma (OR = 0.60, 95 % CI 0.46-0.77, P < 0.001).
      However, MDM2 rs2279744 polymorphism was not associated with the overall survival
      of patients with osteosarcoma (codominant model, HR = 1.01, 95 % CI 0.53-1.91, P
      = 0.98; recessive model, HR = 1.07, 95 % CI 0.54-2.11, P = 0.85; dominant model,
      HR = 1.04, 95 % CI 0.65-1.66, P = 0.87). The meta-analysis suggests that MDM2
      polymorphisms have some effects on the risk of osteosarcoma but have no effect on
      the survival of patients with osteosarcoma. Future studies are needed to further
      assess the effects of MDM2 polymorphisms on the risk and survival of
      osteosarcoma.

PMID- 24122203
TI  - Human kallikrein 2 (KLK2) promotes prostate cancer cell  growth via function as a
      modulator to promote  the ARA70-enhanced androgen receptor transactivation.
AB  - Recent data suggested that tissue human kallikrein 2 (KLK2) might be involved in
      the carcinogenesis and tumor metastasis of prostate cancer (PCa). However, the
      detailed pathophysiological roles of KLK2 in PCa remain unclear. We report here
      that KLK2 may be treated as a potential therapeutic target in castration
      resistant PCa (CRPC). Histologic analyses show that the increased KLK2 expression
      is correlated with higher cell proliferation rate and lower cell apoptosis index
      in CRPC specimens. Adding functional KLK2 cDNA into high passage LNCaP cells led
      to increased cell growth, and knockdown of KLK2 expression with KLK2-siRNA in
      LNCaP cells resulted in increased cell apoptosis with cell growth arrest at the
      G1 phase. Results from in vitro colony formation assay and in vivo xenografted
      PCa tissues also demonstrated that targeting KLK2 led to suppressed growth of PCa
      in the castration-resistant stage. Further mechanism dissection shows that KLK2
      may cooperate with the AR coregulator, ARA70, to enhance AR transactivation that
      may result in alteration of PCa formation. Together, these results suggested KLK2
      might become a new therapeutic target to battle the CRPC and KLK2-siRNA may be
      developed as an alternative approach to suppress PCa growth.

PMID- 24122204
TI  - Milk fat globule epidermal growth factor 8 serves a novel  biomarker of
      opisthorchiasis-associated cholangiocarcinoma.
AB  - Milk fat globule epidermal growth factor 8 (MFG-E8) is a pleiotropic secreted
      glycoprotein to play roles in mediating immune tolerance and homeostasis
      maintenance and enhancing angiogenesis. To evaluate its value as a biomarker in
      opisthorchiasis-associated cholangiocarcinoma (CCA), the present study
      investigated MFG-E8 expression kinetics during the tumorigenesis in Opisthorchis
      viverrini infection-induced CCA, and demonstrated its expression in the tumor
      tissues of CCA patients and its serum level among them. During the tumorigenesis
      of CCA, MFG-E8 expression was increased in a time-dependent manner with the
      pathological processes. Absolutely higher expression of MFG-E8 messenger RNA was
      detected in the tumor tissues from CCA patients, compared with those in adjacent
      tissues. Immunobiochemical analysis showed that more than 90% CCA cases were
      positive and the positive reaction located in the membrane and cytoplasm of the
      tumor cells. Moreover, the average serum level in the CCA patients was
      significantly higher than that in healthy individuals and those with O. viverrini
      infection or other parasitosis. Correlation analysis of MFG-E8 expression with
      CCA clinicopathology revealed that a high expression of MFG-E8 protein was
      significantly bound with a poor differentiation, pathological advanced stage, and
      metastasis of CCA. The multivariation analysis indicated that MFG-E8 was an
      independent prognostic factor. In addition, short hairpin RNA-mediated MFG-E8
      knockdown in CCA cell line obviously suppressed the cell proliferation. Our
      results strongly suggested that MFG-E8 is a promising biomarker for the
      diagnosis, prognosis, and therapy target of opisthorchiasis-associated CCA.

PMID- 24122205
TI  - Characterization of CD44 variant expression in head and neck  squamous cell
      carcinomas.
AB  - CD44 is a complex family of molecules, associated with aggressive malignancies
      and cancer stem cells. However, the role of CD44 variants in tumor progression
      and treatment resistance is not clear. In this study, the expression of CD44 and
      its variants was assessed in head and neck squamous cell carcinomas (HNSCC).
      Furthermore, subpopulations of cells expressing high amounts of CD44 variants
      were identified and characterized, for e.g., cell cycle phase and
      radioresistance. Results revealed high and homogenous CD44 and CD44v7 expression
      in four cell lines and CD44v4 and CD44v6 in three cell lines. CD44v3 was highly
      expressed in two cell lines, whereas CD44v5, CD44v7/8, CD44v10, CD133, and CD24
      demonstrated no or moderate expression. Moreover, a subpopulation of very high
      CD44v4 expression was identified, which is independent of cell phase,
      demonstrating increased proliferation and radioresistance. In cell starvation
      experiments designed to enrich for cancer stem cells, a large population with
      dramatically increased expression of CD44, CD44v3, CD44v6, and CD44v7 was formed.
      Expression was independent of cell phase, and cells demonstrated increased
      radioresistance and migration rate. Our results demonstrate that the
      heterogeneity of tumor cells has important clinical implications for the
      treatment of HNSCC and that some of the CD44 variants may be associated with
      increased radioresistance. Highly expressed CD44 variants could make interesting
      candidates for selective cancer targeting.

PMID- 24122206
TI  - Association between glutathione S-transferase T1 null  genotype and glioma
      susceptibility: a meta-analysis.
AB  - The relationship between genetic polymorphisms of glutathione S-transferase (GST)
      and the development of glioma has been investigated in several epidemiologic
      studies. However, these studies report inconsistent results. In order to get this
      precise result, a meta-analysis was conducted by calculating the pooled odds
      ratios (OR) and the 95% confidence intervals (95 % CI). Eleven case-control
      research studies with a total of 2,416 glioma cases and 4,850 controls were
      included into this meta-analysis. The combined results based on all studies
      showed that there was no significant association between the GSTT1 null allele
      and glioma risk (OR = 1.188, 95% CI = 0.929-1.520, P(heterogeneity) = 0.003, P =
      0.170). In the subgroup analysis, the same results were found in our work. There
      was no risk of publication bias in this meta-analysis. Our results suggest that
      GSTT1 null genotype was not associated with the increased risk of glioma.

PMID- 24122207
TI  - MTHFR C677T polymorphism contributes to the risk  for gastric cancer.
AB  - Methylenetetrahydrofolate reductase (MTHFR) has been demonstrated to be involved
      in carcinogenesis. Increasing individual studies have investigated the role of
      MTHFR C677T polymorphism in gastric cancer pathogenesis, but with inconsistent
      findings. The aim of this study was to clarify the potential association of the
      MTHFR C677T polymorphism with gastric cancer risk by pooling all available data
      from published case-control studies. We searched the PubMed, Embase, Web of
      Science, and Wanfang databases for all relevant publications to date. The pooled
      odds ratio (OR) with corresponding 95 % confidence interval (95% CI) was
      calculated. Stratified analysis and sensitivity analysis were also carried out to
      estimate the strength of this association. A total of 25 case-control studies
      with 6,572 cases and 9,584 controls were retrieved. Overall, the ORs under five
      contrast models indicated that the MTHFR C677T variant was positively associated
      with gastric cancer risk (ORT vs. C = 1.21, 95% CI 1.10-1.34, P(OR) < 0.001;
      OR(TT vs. CC) = 1.47, 95% CI 1.22-1.76, P(OR) < 0.001; OR(TC vs. CC) = 1.20, 95%
      CI 1.03-1.40, P(OR) = 0.022; OR(TT + TC vs. CC) = 1.27, 95% CI 1.10-1.47, P(OR) =
      0.001; OR(TT vs. CC + TC) = 1.29, 95% CI 1.15-1.46, P(OR) < 0.001). Stratified
      analyses according to ethnicity and source of controls further confirmed the
      significant correlations. The current meta-analysis provides strong evidence that
      the MTHFR C677T polymorphism may be a risk factor for gastric cancer among Asians
      and Caucasians.

PMID- 24122208
TI  - Fn14 promotes differentiation of human mesenchymal stem cells into heart valvular
      interstitial cells by phenotypic characterization.
AB  - Despite the fact that tissue engineered heart valves (TEHV) hold great promise
      for heart valve disease treatment, one of the challenges is to find suitable
      seeding cells. Bone marrow derived mesenchymal stem cells (MSCs) were considered
      to be one of the best seed cell sources. In this study we propose a novel
      approach to promote stem cell differentiation into the seed cells of TEHV,
      valvular interstitial cells (VICs). Newly induced MSCs (iMSCs) were created from
      a co-culture niche in which healthy human donor derived MSCs were co-cultured
      with cardiac fibroblasts (H9C2 cell line). Then iMSCs were transfected with
      either a mock vector (iMSCs(mock) ) as controls or with a vector that
      overexpresses thefibroblast inducible factor 14 (Fn14) gene (iMSCs(Fn14) ).
      Immunofluorescence staining was performed to assay VIC differentiation. Western
      blot analysis was performed to analyze the involved signaling pathway. The
      results demonstrate that the expression of alpha-smooth muscle actin (SMA) was
      significantly higher in iMSCs(Fn14) as compared with iMSC(mock) , and MSC, and
      also had higher co-alignment of alpha-actinin and stress fiber (F-actin) in
      bundles. Additionally, increased biosynthesis of extracellular matrix (ECM)
      proteins including collagen I, collagen III, and fibronection were observed in
      iMSCs(Fn14) in comparison with iMSCs(mock) . These data observed in iMSCs(Fn14)
      were in accordance with VIC phenotype from normal heart valves. In addition, the
      PI3K/Akt signaling pathway was activated in iMSCs(Fn14) which allowed higher Akt
      phosphorylation (p-Akt) levels and SMA levels, whereas, it was attenuated by
      LY294002 (PI3K/Akt inhibitor). These new findings of the effect of Fn14 on VIC
      like cell differentiation may provide a novel therapeutic strategy for heart
      valve disease treatment.

PMID- 24122209
TI  - Mouse tumour models to guide drug development and identify resistance mechanisms.
AB  - We need improved, translatable and predictive tumour models for the evaluation of
      response and the evolution of resistance to targeted therapeutics. We provide a
      review of the use of different types of preclinical tumour models to evaluate
      novel anticancer agents, and model the rapidly evolving landscape of resistance
      to targeted therapy. We focus on describing the various preclinical models
      available for candidate drug development and design considerations for
      preclinical experiments, depending on the aspect of drug action being
      interrogated. We discuss selected examples of how experimental findings have
      translated into clinical outcomes for targeted agents, predicted mechanisms that
      drive resistance and strategies to overcome the evolution thereof. We discuss
      challenges in preclinical experimental design and interpretation and possible
      improvements in animal models of therapeutic response and resistance, with an
      emphasis on improved translation of experimental research into clinical practice.

PMID- 24122210
TI  - Correlation between the use of 'over-the-counter' medicines and adherence in
      elderly patients on multiple medications.
AB  - Background Medication adherence is a multifaceted issue that is influenced by
      various factors. One factor may be the concurrent use of over-the-counter (OTC)
      medicines. The use of OTC medicine has been reported as common amongst elderly
      patients. Objective To determine if a correlation exists between the use of OTC
      medicines and adherence to prescribed medications in elderly patients. Setting
      Non-institutionalised elderly patients in Denmark. Methods Elderly unassisted
      patients aged >=65 prescribed five or more prescription drugs were included in
      the study. Information on the use of concurrent OTC medications (herbal
      medicines, dietary supplements, or non-prescribed drugs) was elicited during home
      visit interviews. Prescription drug adherence was determined by pill counts. A
      patient was categorised as non-adherent if the mean adherence rate for all drugs
      consumed was <80 %. Different sensitivity analyses were made where adherence was
      defined different. Main outcome measure Medication adherence based on pill-count.
      Results A total of 253 participants included 72 % who used OTC medicines and 11 %
      who did not adhere to their prescriptions. Users of OTC medicines, however, were
      significantly more likely to be adherent than were non-users (odds ratio 0.41; 95
      % confidence interval 0.18-0.91). Sensitivity analyses where adherence was
      defined different show no relationship between adherence and use of OTC medicine.
      Furthermore, separate analyses of herbal medicines, dietary supplements, or non
      prescribed drugs did not correlate with adherence to prescriptions. Conclusion
      Amongst elderly patients on multiple medications a positive relationship was
      found between the overall use of OTC medicines and adherence to prescription
      drugs, in contrast to none when adherence were defined different or herbal
      medicines, dietary supplements, or non-prescribed drugs were analysed separately.

PMID- 24122211
TI  - Heat and water stress induce unique transcriptional signatures  of heat-shock
      proteins and transcription factors in grapevine.
AB  - Grapevine is an extremely important crop worldwide.In southern Europe, post
      flowering phases of the growth cycle can occur under high temperatures, excessive
      light, and drought conditions at soil and/or atmospheric level. In this study, we
      subjected greenhouse grown grapevine, variety Aragonez, to two individual abiotic
      stresses, water deficit stress(WDS), and heat stress (HS). The adaptation of
      plants to stress is a complex response triggered by cascades of molecular net
      works involved in stress perception, signal transduction, and the expression of
      specific stress-related genes and metabolites. Approaches such as array-based
      transcript profiling allow assessing the expression of thousands of genes in
      control and stress tissues. Using microarrays, we analyzed the leaf
      transcriptomic profile of the grapevine plants. Photosynthesis measurements
      verified that the plants were significantly affected by the stresses applied.
      Leaf gene expression was obtained using a high-throughput transcriptomic
      grapevine array, the 23K custom-made Affymetrix Vitis GeneChip. We identified
      1,594 genes as differentially expressed between control and treatments and
      grouped them into ten major functional categories using MapMan software. The
      transcriptome of Aragonez was more significantly affected by HS when compared
      with WDS. The number of genes coding for heat-shock proteins and transcription
      factors expressed solely in response to HS suggesting their expression as unique
      signatures of HS. However, across-talk between the response pathways to both
      stresses was observed at the level of AP2/ERF transcription factors.

PMID- 24122212
TI  - Alkaline protease from Thermoactinomyces sp. RS1 mitigates  industrial pollution.
AB  - Proteases have found a wide application in the several industrial processes, such
      as laundry detergents, protein recovery or solubilization, prion degradation,
      meat tenderizations, and in bating of hides and skins in leather industries. But
      the main hurdle in industrial application of proteases is their economical
      production on a large scale. The present investigation aimed to exploit the
      locally available inexpensive agricultural and household wastes for alkaline
      protease production using Thermoactinomyces sp. RS1 via solid-state fermentation
      (SSF) technique. The alkaline enzyme is potentially useful as an additive in
      commercial detergents to mitigate pollution load due to extensive use of caustic
      soda-based detergents. Thermoactinomyces sp. RS1 showed good protease production
      under SSF conditions of 55  degrees C, pH 9, and 50 % moisture content with
      potato peels as solid substrate. The presented findings revealed that crude
      alkaline protease produced by Thermoactinomyces sp. RS1 via SSF is of potential
      application in silver recovery from used X-ray films.

PMID- 24122213
TI  - Developmental drift as a mechanism for aging: lessons from nematodes.
AB  - Aging is a universal biological process that afflicts every creature on this
      planet. To date, we have a very poor understanding of what actually causes this
      degeneration. A commonly held view is that aging is the result of damage
      accumulation over a lifetime. However, research has shown that aging is not only
      the result of wear and tear in the organism, but also of genetic programs
      involved in organismal development that go awry as selective pressure is
      released. This review focuses on Wnt signalling pathways and discusses how these
      genetic programs orchestrate changes in the organism that could cause aging.

PMID- 24122214
TI  - The systems biology of mitochondrial fission and fusion and implications for
      disease and aging.
AB  - Mitochondria organize themselves as dynamic populations within a cell, by
      undergoing continuous cycles of fission and fusion. The spatio-temporal
      distribution and abundance of mitochondria determines the cell's energy budget
      and is thus intimately linked to the cell's response to environmental stimuli
      during aging. The dynamic balance of mitochondrial fission and fusion can be
      studied in terms of antagonistic subpopulations that regulate the mitochondrial
      responses in space and time. The dynamic nature of these processes motivates
      mathematical modelling and the simulation of such complex process. In several
      neurodegenerative and metabolic diseases the dynamic balance of fission and
      fusion is disturbed. However, how this dynamics plays a role in the progression
      of diseases is largely unclear. Fission and fusion help mitochondria to regulate
      cellular energy (ATP) levels, and minimize accumulation of harmful oxidized
      material called reactive oxygen species which accelerate mutations in
      mitochondrial DNA (mtDNA) during aging. We discuss how systems biology approaches
      can be used to investigate the mechanisms controlling the fission-fusion dynamics
      under two categories: dissecting the design of its molecular regulatory motifs,
      and understanding complex mitochondrial responses through their population level
      interactions. This will help us to understand how different regulatory mechanisms
      regulate the ATP and mutation (mtDNA) landscape of mitochondria to a variety of
      environmental stimuli in order to maintain their function during aging.

PMID- 24122215
TI  - Spatial extraction model for soil environmental quality of anomalous areas in a
      geographic scale.
AB  - An approach to establish a soil environmental assessment model was proposed to
      evaluate the soil environmental quality level. The kriging technique and a self
      organizing map (SOM) were integrated to investigate the soil environmental
      quality in a geographic information system (GIS). In this study, SOM was applied
      to categorize the data set of nine heavy metals in topsoil. A total of 261
      topsoil samples were collected to determine the concentrations of Cu, Pb, Zn, Cd,
      Ni, Cr, Hg, As, and Mn. The samples were clustered into three classes by SOM and
      visualized by GIS. The results show that different environmental quality
      categories are significantly different and that the soil environmental quality
      assessment model is effective.

PMID- 24122216
TI  - Sudden unexpected death in epilepsy or voodoo heart: analysis of heart/brain
      connections.
AB  - Sudden unexpected death in epilepsy (SUDEP) affects up to 5000 patients a year in
      the United States alone. The exact pathophysiologic processes of are unknown.
      Profound autonomic dysregulation driving cardiac and respiratory dysfunction is
      likely. Available evidence from monitored deaths suggests that fatal
      tachyarrhythmias are not primarily responsible although near deaths due to
      ventricular arrhythmias have been reported. Genetic "neuro-cardiac"
      channelopathies affecting brain function, central respiratory processes, and
      cardiac rhythm have been hypothesized. These, as well as serotonergic mechanisms
      affecting brainstem homeostasis of cardiac and respiratory function are important
      areas of current and future SUDEP research. 

PMID- 24122217
TI  - Anti-ESBL activity of silver nanoparticles biosynthesized using soil Streptomyces
      species.
AB  - Emergence of antibiotic resistance by bacteria has become a serious threat for
      public health worldwide. In this study, Streptomyces isolated from fertile soil
      sample was tested for biosynthesis of silver nanoparticles (AgNps) using cell
      free supernatant and synthesized AgNps were screened for anti-ESBL (extended
      spectrum b-lactamase) activity against multi-drug resistant (MDR) ESBL-producing
      strain Klebsiella pneumoniae (ATCC 700603) and other medically important
      pathogens. Synthesis of AgNps was confirmed by change in pale yellow color to
      dark brown color and characteristic absorption spectra at 420 nm. The XRD
      spectrum displayed typical peaks of crystalline silver and EDAX analysis showed a
      major signal for silver. FTIR spectra revealed prominent peaks at 3,294 cm-1 (NH
      stretching due to amide group), 2,952 cm-1 (aldehydic C-H stretching) 1,658 cm-1
      indicating the presence of carbonyl group. AgNps were spherical in shape with
      size ranging from 20 to 70 nm. The synthesized AgNps showed significant
      antimicrobial activity against standard ESBL pathogen K. pneumoniae (22 mm), 21
      mm against clinical ESBL isolate E. coli and 16 mm against clinical ESBL isolates
      K. pneumoniae and Citrobacter species, respectively. The results of this study
      suggest that AgNps synthesized by Streptomyces sp. VITSJK10 can be used as a
      potential alternative to control MDR ESBL pathogens. The present study aimed for
      green synthesis of AgNps using Streptomyces species and to explore its anti-ESBL
      activity.

PMID- 24122218
TI  - Body mass and smoking are modifiable risk factors for recurrent bladder cancer.
AB  - BACKGROUND: In the Western world, bladder cancer is the fourth most common cancer
      in men and the eighth most common in women. Recurrences frequently occur, and
      continued surveillance is necessary to identify and treat recurrent tumors.
      Efforts to identify risk factors that are potentially modifiable to reduce the
      rate of recurrence are needed. METHODS: Cigarette smoking behavior and body mass
      index were investigated at diagnosis for associations with bladder cancer
      recurrence in a population-based study of 726 patients with bladder cancer in New
      Hampshire, United States. Patients diagnosed with non-muscle invasive urothelial
      cell carcinoma were followed to ascertain long-term prognosis. Analysis of time
      to recurrence was performed using multivariate Cox regression models. RESULTS:
      Smokers experienced shorter time to recurrence (continuing smoker hazard ratio
      [HR] = 1.51, 95% confidence interval [CI] = 1.08-2.13). Although being overweight
      (body mass index > 24.9 kg/m(2) ) at diagnosis was not a strong independent
      factor (HR = 1.33, 95% CI = 0.94-1.89), among continuing smokers, being
      overweight more than doubled the risk of recurrence compared to smokers of normal
      weight (HR = 2.67, 95% CI = 1.14-6.28). CONCLUSIONS: These observational results
      suggest that adiposity is a risk factor for bladder cancer recurrence,
      particularly among tobacco users. Future intervention studies are warranted to
      evaluate whether both smoking cessation and weight reduction strategies reduce
      bladder tumor recurrences.

PMID- 24122220
TI  - [Epigenetic analyses - new therapeutic approaches for rheumatic diseases?].

PMID- 24122221
TI  - [Medicine from the computer].
AB  - Small molecules can have a significant effect on human metabolic processes.
      Computational drug design aims at constructing specialized small molecules that
      selectively and efficiently address specific proteins. The basic ideas of
      computational molecular design are presented and it will be shown how a virtual
      protein can be computer designed. This virtual protein can be used to predict the
      binding affinity of given small molecules without having to synthesize them in a
      laboratory. Modern computational drug design goes far beyond the lock and key
      principle. Possible future developments are discussed and a current successful
      example of computational drug design in the field of painkiller medication is
      demonstrated. 

PMID- 24122225
TI  - World region of origin and common mental disorders among migrant women in Spain.
AB  - Migration can affect the mental health of migrants. This cross-sectional study
      has two objectives: (1) to compare the prevalence of common mental disorder (CMD)
      between migrants (n = 458) living in Granada (Spain) and Spanish-born women (n =
      448); (2) within migrants, to analyse the associations of world region of origin,
      other sociodemographic factors and post-migration features with the presence of
      CMD. Participants answered a questionnaire, including sociodemographic
      characteristics, post-migration features and CMD that was measured by Kessler K6
      scale. Logistic regression analyses showed that CMD (K6 >= 13) was significantly
      higher among migrants than Spaniards. Compared with Spaniards, the odds of CMD
      were 3.6 [95 % confidence intervals (CI) 2.1-6.0] and 2.9 (CI 1.6-5.3),
      respectively, for Latin Americans and for Moroccan and other African women. Among
      migrants, Latin Americans as opposed to the reference group (migrants from other
      countries), had higher probability of CMD (OR 2.3, CI 1.1-4.9). This study
      supports the hypothesis that migration leads to mental distress. Consideration of
      world region of origin may clarify the differences observed in mental health
      across different migrant groups.

PMID- 24122226
TI  - Over-expression of CXCR4 on mesenchymal stem cells protect against experimental
      colitis via immunomodulatory functions in impaired tissue.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) are attractive candidates for
      tissue regeneration and immunoregulation in inflammatory bowel disease. However,
      their in vivo reparative capability is limited owing to barren efficiency of
      BMSCs to injury region. Stromal cell-derived factor (SDF-1) plays an important
      role in chemotaxis and stem cell homing through interaction with its specific
      receptor CXC chemokine receptor 4 (CXCR4). The present study was designed to
      investigate the role of SDF-1alpha/CXCR4 axis in the therapeutic effects of
      lentivirus-preconditioned BMSCs for 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      colitis rats. BMSCs were isolated from female Sprague-Dawley rats and identified
      by flow cytometry. Lentiviral transduction was applied to over-express CXCR4/GFP
      (Ad-CXCR4-BMSCs) or null/GFP (Ad-GFP-BMSCs). Efficacy of engraftment was
      determined by the presence of enhanced green fluorescent protein (GFP) positive
      cells. One week after intravenous administration, Ad-GFP-BMSCs failed to colonize
      in the inflamed colon and had no beneficial effect in TNBS-induced colitis.
      Instead, Ad-CXCR4-BMSCs signally ameliorated both clinical and microanatomical
      severity of colitis. Immunofluorescence and western blotting showed that Ad-CXCR4
      BMSCs migrated toward inflamed colon was more efficient than Ad-GFP-BMSCs. The
      therapeutic effect of Ad-CXCR4-BMSCs was mediated by the suppression of pro
      inflammatory cytokines and STAT3 phosphorylation in injured colon. Collectively,
      our data indicated that over-expression CXCR4 led to enhance in vivo mobilization
      and engraftment of BMSCs into inflamed colon where these cells can function as an
      anti-inflammatory and immunomodulatory component of the immune system in TNBS
      induced colitis. 

PMID- 24122227
TI  - Disturbance of intraepithelial lymphocytes in a murine model of acute intestinal
      ischemia/reperfusion.
AB  - Strategically located at the epithelial basolateral surface, intraepithelial
      lymphocytes (IELs) are intimately associated with epithelial cells and maintain
      the epithelial barrier integrity. Intestinal ischemia-reperfusion (I/R)-induced
      acute injury not only damages the epithelium but also affects the mucosal barrier
      function. Therefore, we hypothesized that I/R-induced mucosal damage would affect
      IEL phenotype and function. Adult C57BL/6J mice were treated with intestinal I/R
      or sham. Mice were euthanized at 6 h after I/R, and the small bowel was harvested
      for histological examination and to calculate the transmembrane resistance.
      Occludin expression and IEL location were detected through immunohistochemistry.
      The IEL phenotype, activation, and apoptosis were examined using flow cytometry.
      Cytokine and anti-apoptosis-associated gene expressions were measured through RT
      PCR. Intestinal I/R induced the destruction of epithelial cells and intercellular
      molecules (occludin), resulting in IEL detachment from the epithelium. I/R also
      significantly increased the CD8alphabeta, CD4, and TCRalphabeta IEL
      subpopulations and significantly changed IEL-derived cytokine expression.
      Furthermore, I/R enhanced activation and promoted apoptosis in IELs. I/R-induced
      acute intestinal mucosal damage significantly affected IEL phenotype and
      function. These findings provide profound insight into potential IEL-mediated
      epithelial barrier dysfunction after intestinal I/R.

PMID- 24122228
TI  - Expression of aquaporin-4 water channels in the digestive tract of the guinea
      pig.
AB  - Expression of the aquaporin-4 (AQP4) water channel was systematically studied in
      the digestive tract of the guinea pig using Western blot and immunofluorescence
      techniques. The results showed that AQP4 was expressed widely in different
      segments of the guinea pig digestive tract. AQP4-immunoreactivity was confined to
      parietal cells in the stomach, and absorptive and glandular epithelial cells of
      small and large intestine. AQP4 protein was also expressed by enteric glial cells
      of submucosal and myenteric ganglia and primary nerve trunks. AQP4 was expressed
      by both type I and type II enteric gliocytes, but not by type III or type IV
      enteric gliocytes, indicating that enteric gliocytes have a heterogeneous
      distribution in the gut wall. In addition, different patterns of AQP4 expression
      in the enteric nervous system of human, guinea pig, rat and mouse colon mucosa
      were identified: in rat and mouse AQP4 was localised to a small subpopulation of
      neurons; in the guinea pig AQP4 was localised to enteric glial cells; and in the
      human colon mucosa, AQP4 was also detected mainly in the glial cells. It has been
      speculated that AQP4 may be involved in water transport in the gastrointestinal
      tract. Its role in enteric neurons and glia is unknown, but, by analogy with the
      brain, AQP4 may be involved in the formation and resolution of edema. 

PMID- 24122229
TI  - Echocardiographic definition of restrictive patent foramen ovale (PFO).

PMID- 24122230
TI  - Ultra-low-dose ketamine infusion for ischemic limb pain.

PMID- 24122231
TI  - Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.
AB  - Radiotherapy is one of the main treatments for clinical cancer therapy. However,
      its application was limited due to lack of radiosensitivity in some cancers.
      Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that
      specifically inhibits the biochemical functions of HDAC and is demonstrated to be
      an active anticancer drug. However, whether it could sensitize colon cancer to
      radiation is not clear. Our results showed that TSA enhanced the radiosensitivity
      of colon cancer cells as determined by CCK-8 and clonogenic survival assay.
      Moreover, apoptotic cell death induced by radiation was enhanced by TSA
      treatment. Additionally, TSA also induced autophagic response in colon cancer
      cells, while autophagy inhibition led to cell apoptosis and enhanced the
      radiosensitivity of colon cancer cells. Our data suggested that inhibition of
      cytoprotective autophagy sensitizes cancer cell to radiation, which might be
      further investigated for clinical cancer radiotherapy.

PMID- 24122232
TI  - Autoantibodies against p16 protein-derived peptides  may be a potential biomarker
      for non-small cell lung cancer.
AB  - Overexpression of tumor-associated antigens (TAAs) has been reported in many
      types of cancer and may trigger secretion of their autoantibodies. The present
      work was thus designed to test whether circulating antibody to p16 protein
      derived antigens was altered in lung cancer. Two hundred seventy-one patients
      with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age,
      gender, and smoking history were recruited in this study. The levels of
      circulating anti-p16 IgA and IgG antibodies were tested using an enzyme-linked
      immunosorbent assay (ELISA) developed in-house with linear peptide antigens
      derived from p16 protein. Student's t test showed that patients with NSCLC had a
      significant higher level of anti-p16 IgG antibody than control subjects (t =
      2.74, P = 0.0063) but did not have a significant increase in IgA antibody levels
      (t = 1.92, P = 0.056). The sensitivity against >90% specificity was 19.7% for the
      IgG assay with an inter-assay deviation of 11.6%, and 10.3% for the IgA assay
      with an inter-assay deviation of 14.7%. Based on a cut-off value determined by
      the 99th percentile of control IgG levels, the anti-p16 IgG positivity was 6.7%
      in patients with NSCLC compared to 0.88% in control subjects (chi (2) = 10.58, P
      = 0.001, OR = 7.97, 95% CI 1.84-34.85). Circulating anti-p16 IgG levels were
      increased with stages of NSCLC, and patients with stage IV NSCLC had the highest
      IgG level among all four stages (t = 2.42, P = 0.016, compared with the control
      group). Pearson correlation analysis showed a significant correlation between
      circulating levels of IgA and IgG in the patient group (r = -0.2, df = 236, P =
      0.0021) but not in the control group (r = -0.1, df = 205, P = 0.146). Circulating
      IgG antibody to p16 protein may be a potential biomarker with prognostic values
      for lung cancer.

PMID- 24122233
TI  - Low level of high-density lipoprotein cholesterol correlates  with poor prognosis
      in extranodal natural  killer/T cell lymphoma.
AB  - Studies have found that lymphoma patients often exhibit abnormal lipid
      metabolism, and a decrease in serum high-density lipoprotein cholesterol (HDL-C)
      may occur during lymphomagenesis and tumor growth. However, no literatures have
      investigated the role of HDL-C in patients with extranodal natural killer/T cell
      lymphoma (ENKTL). In this study, we retrospectively reviewed the HDL-C level in
      107 patients newly diagnosed with ENKTL that received either l-asparaginase-based
      regimen or EPOCH regimen as induction chemotherapy, and evaluated its prognostic
      value. The mean level of HDL-C was 1.10 mmol/L (range, 0.15-2.63), and the HDL-C
      level was significantly lower in patients with elevated LDH and beta 2
      microglobulin (beta2-MG) (p = 0.017 and 0.001, respectively) and those who
      underwent disease progression and died (p = 0.031 and 0.007, respectively). In
      univariate survival analysis, higher Eastern Cooperative Oncology Group
      performance status score (>=1), Ann Arbor stage III-IV, elevated LDH, higher
      international prognostic index (IPI) score (>=2 vs. 1 vs. 0), decreased HDL-C
      level (<40 mg/dL), elevated beta2-MG level, and response status after induction
      chemotherapy correlated significantly with poor progression-free survival (PFS)
      and overall survival (OS) (p < 0.05). In a multivariate Cox regression model that
      included IPI score, HDL-C level, beta2-MG level, and response status after
      induction chemotherapy, it was found that HDL-C level and response status after
      chemotherapy were independent prognostic factors for OS (p = 0.014 and 0.010,
      respectively) and PFS (p = 0.016 and 0.020, respectively). In conclusion, HDL-C
      was found to be a valuable independent prognostic factor in ENKTL, and the
      mechanism needs to be further investigated, which may offer the possibility of
      therapeutic targets.

PMID- 24122234
TI  - Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human
      leukemia cells.
AB  - This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)
      N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP
      2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell
      invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937,
      Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both
      MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in
      leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine
      elicited ROS generation induced JNK and p38 MAPK activation but reduced the
      phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation
      were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and
      promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up
      regulation of protein phosphatase 2A catalytic subunit alpha (PP2Acalpha) in
      amsacrine-treated U937 cells. Okadaic acid (PP2A inhibitor) treatment increased
      MMP-2/MMP-9 mRNA stability in amsacrine-treated cells, whereas PP2Acalpha over
      expression increased MMP-2/MMP-9 mRNA decay. Amsacrine-induced MMP-2/MMP-9 down
      regulation was also related to PP2Acalpha up-regulation on Jurkat, HL-60, K562,
      KU812, and MEG-01 cells. Collectively, our data indicate that amsacrine induces
      MMP-2/MMP-9 down-regulation via simultaneous suppression of genetic transcription
      and mRNA stability in human leukemia cells.

PMID- 24122235
TI  - The identification of the nitrate assimilation related genes in the novel
      Bacillus megaterium NCT-2 accounts for its ability to use nitrate as its only
      source of nitrogen.
AB  - Bacillus megaterium NCT-2 is a novel bacterium that can utilize nitrate as its
      only nitrogen source for growth.The nitrate assimilation related genes that are
      involved in this process would be expected to be crucial. However, little is
      known about the genomic background of this bacterium,let alone the sequences of
      the nitrate assimilation related genes. In order to further investigate the
      nitrate assimilation function of the NCT-2, genome sequencing was performed.After
      obtaining the fine map of the NCT-2 genome, which was submitted to the NCBI
      GenBank (AHTF00000000), the sequences of the nitrate assimilation related genes
      (the nitrate reductase electron transfer subunit nasB and the nitrate reductase
      catalytic subunit nasC, the nitrite reductase [NAD(P)H]large subunit nasD and the
      nitrite reductase [NAD(P)H] small subunit nasE, and the glutamine synthetase
      glnA) were identified.Multiple alignments were performed to find out the sequence
      identities of the nitrate assimilation related genes to that of their similar
      species. Through KEGG signaling mapping search, the nitrate assimilation related
      genes were revealed to be located in the nitrogen metabolism signaling pathway.
      The putative 3D protein structures of these genes were modeled by SWISS MODEL,
      and shown to be highly similar to the nitrate assimilation related genes in the
      PDB database. Finally, the sequence validity of the nitrate assimilation related
      genes was verified by PCR with specifically designed primers.

PMID- 24122237
TI  - Adult mortality or morbidity is not increased in childhood-onset growth hormone
      deficient patients who received pediatric GH treatment: an analysis of the
      Hypopituitary Control and Complications Study (HypoCCS).
AB  - BACKGROUND: The French Safety and Appropriateness of Growth Hormone treatments in
      Europe (SAGhE) cohort has raised concern of increased mortality risk during
      follow-up into adulthood in certain patients who had received growth hormone (GH)
      treatment during childhood. The Hypopituitary Control and Complications Study
      monitored mortality and morbidity of adult GH-deficient patients including those
      with childhood-onset GH deficiency (COGHD) who received GH treatment as children.
      PURPOSE: Evaluate risk of mortality, cancer, myocardial infarction (MI) and
      stroke in a prospective observational study. METHODS: COGHD patients [n = 1,204,
      including 389 diagnosed with idiopathic COGHD (ICOGHD)] had received pediatric GH
      treatment. Standardized mortality ratios (SMRs), and cancer standardized
      incidence ratios (SIRs) in patients without a prior cancer were estimated
      relative to reference populations. Crude incidence rates were estimated for MI
      and stroke. RESULTS: No increased mortality or cancer incidence was observed, as
      compared with reference populations, during a follow-up of 3.7 +/- 3.3 years
      (mean +/- SD). The overall SMR for COGHD was 1.14 [95 % confidence interval (CI)
      0.55-2.10], and for ICOGHD, 0.33 (0.01-1.84). The overall cancer SIR for COGHD
      was 0.27 (0.01-1.50), and for ICOGHD, 0.00 (0.00-2.45). No incident case of MI
      was reported. The crude stroke incidence rate [181.3 per 100,000 person-years] in
      COGHD patients was consistent with the rates reported in reference populations.
      No incident case of stroke was identified in ICOGHD patients who are presumed to
      have no increased stroke risk factors. CONCLUSIONS: The results indicate no
      increased risk of mortality or incidence of cancer, stroke, or MI in adult GH
      deficient patients who had previously received pediatric GH treatment.

PMID- 24122238
TI  - JNK is necessary for oligodendrocyte precursor cell proliferation induced by the
      conditioned medium from B104 neuroblastoma cells.
AB  - The conditioned medium from B104 neuroblastoma cells (B104CM) induces
      proliferation of oligodendrocyte progenitor cells (OPCs) in vitro. Our previous
      study showed that phosphorylation of extracellular signal-regulated protein
      kinase(s), not PI3K or p38, is key to B104CM-induced OPC proliferation. However,
      whether there are still other signaling pathways that are also involved in B104CM
      induced proliferation remains unknown. In the present study, we evaluated the
      implication of c-Jun N-terminal kinase (JNK) signaling pathway in the B104CM
      induced proliferation of OPCs using the specific inhibitor of JNK. We provided
      convincing evidence for the first time that the phosphorylation of JNK is
      necessary for OPC proliferation induced by B104CM in vitro. Moreover, the
      activation of JNK results in subsequent expressions of c-jun, c-fos, and c-myc,
      which initiates proliferation of OPCs. Collectively, these results suggest that
      JNK is also necessary for B104CM-induced OPC proliferation.

PMID- 24122236
TI  - Towards the introduction of the 'Immunoscore' in the classification of malignant
      tumours.
AB  - The American Joint Committee on Cancer/Union Internationale Contre le Cancer
      (AJCC/UICC) TNM staging system provides the most reliable guidelines for the
      routine prognostication and treatment of colorectal carcinoma. This traditional
      tumour staging summarizes data on tumour burden (T), the presence of cancer cells
      in draining and regional lymph nodes (N) and evidence for distant metastases (M).
      However, it is now recognized that the clinical outcome can vary significantly
      among patients within the same stage. The current classification provides limited
      prognostic information and does not predict response to therapy. Multiple ways to
      classify cancer and to distinguish different subtypes of colorectal cancer have
      been proposed, including morphology, cell origin, molecular pathways, mutation
      status and gene expression-based stratification. These parameters rely on tumour
      cell characteristics. Extensive literature has investigated the host immune
      response against cancer and demonstrated the prognostic impact of the in situ
      immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been
      defined to quantify the in situ immune infiltrate. In colorectal cancer, the
      Immunoscore may add to the significance of the current AJCC/UICC TNM
      classification, since it has been demonstrated to be a prognostic factor superior
      to the AJCC/UICC TNM classification. An international consortium has been
      initiated to validate and promote the Immunoscore in routine clinical settings.
      The results of this international consortium may result in the implementation of
      the Immunoscore as a new component for the classification of cancer, designated
      TNM-I (TNM-Immune).

PMID- 24122240
TI  - Medication costs by glucose tolerance stage in younger and older women and men:
      results from the population-based KORA survey in Germany.
AB  - To estimate medication costs in individuals with diagnosed diabetes, undetected
      diabetes, impaired glucose regulation and normal blood glucose values in a
      population-based sample by age and sex.Using the KORA F4 follow-up survey,
      conducted in 2006-2008 (n=2611, age 40-82 years), we identified individuals'
      glucose tolerance status by means of an oral glucose tolerance test. We assessed
      all medications taken regularly, calculated age-sex specific medication costs and
      estimated cost ratios for total, total without antihyperglycemic drugs, and
      cardiovascular medication, using multiple 2-part regression models.Compared to
      individuals with normal glucose values, costs were increased in known diabetes,
      undetected diabetes and impaired glucose regulation, which was more pronounced in
      participants aged 40-59 years than in those aged 60-82 years (cost ratios for all
      medications: 40-59 years: 2.85; 95%-confidence interval: 1.78-4.54, 2.00; 1.22
      3.29 and 1.53; 1.12-2.09; 60-82 years: 2.04; 1.71-2.43, 1.17; 0.90-1.51 and 1.09;
      0.94-1.28). Compared to individuals with diagnosed diabetes, costs were
      significantly lower among individuals with impaired glucose regulation across all
      age and sex strata, also when antihyperglycemic medication was excluded (40-59
      years: 0.60; 0.36-0.98, 60-82 years: 0.74; 0.60-0.90; men: 0.72; 0.56-0.93;
      women: 0.72; 0.54-0.96).We could quantify age- and sex-specific medication costs
      and cost ratios in individuals with diagnosed diabetes, undetected diabetes and
      impaired glucose regulation compared to those with normal glucose values, using
      data of a population-based sample, with oral glucose tolerance test-based
      identification of diabetes states. These results may help to validly estimate
      cost-effectiveness of screening and early treatment or prevention of diabetes. 

PMID- 24122239
TI  - Immunohistochemical characteristics and distribution of neurons in the
      paravertebral, prevertebral and pelvic ganglia supplying the urinary bladder in
      the male pig.
AB  - The distribution and chemical coding of neurons supplying urinary bladder in the
      male pig were studied in the sympathetic chain ganglia, inferior mesenteric
      ganglia and anterior pelvic ganglia. The combined retrograde tracing and
      immunohistochemistry for tyrosine hydroxylase (TH), dopamine beta-hydroxylase
      (DBH), neuropeptide Y (NPY), somatostatin(SOM), galanin (GAL), vasoactive
      intestinal polypeptide(VIP), nitric oxide synthase (NOS), calcitonin gene related
      peptide (CGRP), substance P (SP), choline acetyltransferase (ChAT) and vesicular
      acetylcholine transporter(VAChT) were applied in the experiment. Bladder
      projecting neurons were found in all the ganglia studied. The majority of
      sympathetic ganglia neurons (inferior mesenteric ganglia and sympathetic chain
      ganglia) expressed immunoreactivity(IR) to DBH. In sympathetic chain ganglia
      these neurons simultaneously expressed NPY, GAL or VAChT,while in inferior
      mesenteric ganglia they contained NPY, SOM and/or GAL. A small number of these
      bladder projecting neurons was VAChT-IR and some contained NPY. In the pelvic
      ganglia bladder-projecting neurons formed two populations: DBH- and VAChT-IR.
      Some of DBH-IR neurons contained IR to NPY, SOM or GAL, while VAChTIR neurons
      were NPY-, SOM- or NOS-IR. The results indicate that sympathetic ganglia contain
      mainly adrenergic neurons,while pelvic ganglia contain both adrenergic and
      cholinergic neurons. All these neurons contain typical combinations of
      neuropeptides.

PMID- 24122241
TI  - Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or
      immunosuppressive therapy.
AB  - Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially
      approved medical treatment for metastatic melanoma, which results in improved
      survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell
      immunoreactions. Therefore, patients may also suffer from immune-related adverse
      events affecting different organs, which are typically treated by high-dose
      corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to
      17% of melanoma patients in clinical trials.Here we present 5 patients with
      metastatic melanoma and 2 patients with prostate cancer who developed
      hypophysitis after ipilimumab therapy. Patients were treated by high-dose
      corticosteroid therapy resulting in the resolution of local inflammation but not
      of pituitary deficiencies. Partial or complete hypopituitarism remained in all
      patients. Pharmacotherapy with high-dose corticosteroids caused complications in
      5 patients, necessitating hospitalization in 4. 2 of the 3 patients with
      progressive disease died, while 3 patients had stable disease and 1 patient
      showed tumor regression after discontinuation of ipilimumab.In summary, with
      regard to safety and simplicity of hormonal substitution therapy we have to
      scrutinize high-dose corticosteroid therapy, though it only improves inflammation
      but not neuro-endocrine function and may cause further morbidity. Regression of
      the tumor depends on the ipilimumab-mediated immune events, in which high-dose
      and long-term corticosteroid therapy for iH appears to be counter-intuitive.
      Herein, we discuss screening and the diagnostic as well as therapeutic management
      of iH in metastatic cancer patients from an endocrinologic perspective. 

PMID- 24122242
TI  - Short-term results of a randomized study between laparoscopic and open surgery in
      elderly colorectal cancer patients.
AB  - BACKGROUND: In surgical treatment of elderly patients, securing the safety of
      surgery and radical cure must be balanced. Our purpose was to verify the safety
      and validity of laparoscopic surgery for the treatment of colorectal cancer in
      elderly patients. METHODS: Patients with cTis-T4a colorectal cancer who were 75
      years or older were randomized to receive open or laparoscopic surgery. Exclusion
      criteria were patients who had a bulky tumor, rectal cancer that required pelvic
      side wall lymphadenectomy, and history of colon resection. Patients were divided
      according to tumor location (right colon, left colon, and rectum). The short-term
      outcomes were compared between the two groups. RESULTS: One hundred patients
      (right 43, left 28, and rectum 29) were registered in each group from August 2008
      to August 2012. There were no differences in patient characteristics between the
      two groups. Three patients were converted from laparoscopic to open, because of
      bleeding, excision of peritoneum metastasis, and patient's desire, respectively.
      In the short-term results (open:laparoscopic), there were significant differences
      in the rates of complications (36:23 %) and ileus (12:4 %), amount of blood loss
      (157:63 mL), and duration of surgery (150:172 min). There were no significant
      differences in the pathological margins, and the number of dissected lymph nodes.
      In the subgroup analysis according to the tumor location, there were significant
      differences in the rate of complications (39.4:22.5 %), amount of blood loss
      (135:42 mL), duration of surgery (139:160 min), and length of postoperative stay
      (13.0:10.0 days) in the colon cancer. There were no significant differences in
      short-term results in the rectal cancer. CONCLUSIONS: Laparoscopic surgery in
      elderly colorectal cancer patients did not result in a difference in radical cure
      compared with open surgery, and the short-term results except the duration of
      surgery were excellent. It is an effective procedure for elderly patients with
      colorectal cancer, especially colon cancer.

PMID- 24122243
TI  - Supervised classification of psychomotor competence in minimally invasive surgery
      based on instruments motion analysis.
AB  - BACKGROUND: Objective assessment of psychomotor skills has become an important
      challenge in the training of minimally invasive surgical (MIS) techniques.
      Currently, no gold standard defining surgical competence exists for classifying
      residents according to their surgical skills. Supervised classification has been
      proposed as a means for objectively establishing competence thresholds in
      psychomotor skills evaluation. This report presents a study comparing three
      classification methods for establishing their validity in a set of tasks for
      basic skills' assessment. METHODS: Linear discriminant analysis (LDA), support
      vector machines (SVM), and adaptive neuro-fuzzy inference systems (ANFIS) were
      used. A total of 42 participants, divided into an experienced group (4 expert
      surgeons and 14 residents with >10 laparoscopic surgeries performed) and a
      nonexperienced group (16 students and 8 residents with <10 laparoscopic surgeries
      performed), performed three box trainer tasks validated for assessment of MIS
      psychomotor skills. Instrument movements were captured using the TrEndo tracking
      system, and nine motion analysis parameters (MAPs) were analyzed. The performance
      of the classifiers was measured by leave-one-out cross-validation using the
      scores obtained by the participants. RESULTS: The mean accuracy performances of
      the classifiers were 71 % (LDA), 78.2 % (SVM), and 71.7 % (ANFIS). No
      statistically significant differences in the performance were identified between
      the classifiers. CONCLUSIONS: The three proposed classifiers showed good
      performance in the discrimination of skills, especially when information from all
      MAPs and tasks combined were considered. A correlation between the surgeons'
      previous experience and their execution of the tasks could be ascertained from
      results. However, misclassifications across all the classifiers could imply the
      existence of other factors influencing psychomotor competence.

PMID- 24122244
TI  - Can we become better robot surgeons through simulator practice?
AB  - INTRODUCTION: There is significant growth in the use of the robotic surgery
      platform in the general surgery community. Current pre-requisites for robot
      surgery training include performing basic tasks on a simulator and achieving a
      minimum overall score for each task. However, there is limited information about
      these tasks related to performance and time required to become proficient. We
      focused on critical tasks that have the highest potential for preventing
      inadvertent injuries, and constructed models to predict how many attempts would
      be needed to master the tasks depending on the user's initial attempt. METHODS
      AND PROCEDURES: This study was conducted using de-identified data collected over
      12 months from the dV-Trainers(r) simulator at our institution. We analyzed tasks
      used in institutional surgical robot credentialing that focused on camera
      manipulation and energy use. Data were extracted from the Camera Targeting,
      Energy Dissection, and Energy Switching exercises focusing on individual metrics
      such as Time to Complete Exercise, Economy of Motion, Misapplied Energy Time, and
      Blood Volume Loss. Mixed linear models looking at sequential attempts and
      specific performance metrics were constructed using IBM SPSS Statistics version
      20. RESULTS: Over 26,000 overall minutes of recorded use was logged in our
      simulator by more than 30 unique users across all exercises. An average of 15
      users performed each of the analyzed exercises, with an average of eight attempts
      per exercise. Based on our models, on average most users would need four to five
      attempts to achieve 80 % proficiency for any given metric. CONCLUSION: Virtual
      reality robotic simulators such as the dv-Trainer(r) can be used by general
      surgeons to become better robotic surgeons. Our data suggests that it can be used
      by a surgeon to predict how much time and effort one would need to spend on the
      simulator in order to become proficient with the robot, especially in critical
      metrics such as camera manipulation and energy application. Surgeons who require
      more attempts to successfully complete tasks may want to consider additional
      training methods, such as proctoring or hands-on laboratories, to improve robot
      surgery proficiency.

PMID- 24122245
TI  - Endoscopic management of high-grade dysplasia and intramucosal carcinoma:
      experience in a large academic medical center.
AB  - BACKGROUND: Esophagectomy has been the standard treatment for Barrett's esophagus
      (BE) with high-grade dysplasia (HGD) and intramucosal cancer (IMC). Recently,
      endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) have become
      the preferred treatment for these patients in some centers. We report a single
      institution series of patients undergoing endoscopic management of HGD and IMC.
      METHODS: Nineteen patients underwent endoscopic treatment for HGD or IMC between
      2009 and 2012. The primary outcome measure was progression of BE necessitating
      esophagectomy. Secondary outcomes included complete eradication of intestinal
      metaplasia (CE-IM), complete eradication of dysplasia (CE-D), recurrence or
      progression of BE or dysplasia, and complications. Patients were followed for a
      median follow-up interval of 19 months following completion of RFA treatment.
      RESULTS: Three patients (16 %) had a presenting diagnosis of IMC, and 16 (84 %)
      were treated for HGD. Twelve (63 %) had long-segment BE; the median length of BE
      was 5 cm. Ten (53 %) patients underwent EMR prior to RFA. CE-D was achieved in 88
      % of patients, and CE-IM was achieved in 65 % of patients. A median of 2 (1-7)
      treatments were required, and there were no immediate post-procedure
      complications. Two patients developed recurrent dysplasia following complete
      eradication of BE, and each case was successfully managed with repeat RFA. Three
      patients (16 %) required esophagectomy within 6 months following RFA. A complete
      surgical resection was achieved in each case, and none of the patients developed
      lymph node metastases. CONCLUSIONS: Complete eradication of HGD and IMC can be
      achieved via endoscopic therapy, thus avoiding esophagectomy in the majority of
      patients. However, a subset of patients will fail this treatment approach and
      will require surgical resection. With aggressive endoscopic treatment and
      surveillance, these patients can be identified at an early stage while curative
      resection is still possible.

PMID- 24122246
TI  - Real-time endoscopic pathology assessment of colorectal polyps.

PMID- 24122247
TI  - Evidence of positive selection at codon sites localized in the C-terminal peptide
      of ORC6.
AB  - Origin recognition complex 6 (Orc6) plays a central role in the initiation of DNA
      replication in all eukaryotic systems. The exact contribution of Orc6 to
      replication initiation has yet to be elucidated. Here, we analyzed the
      evolutionary dynamics of Orc6 in 15 vertebrates. Positive selection was detected
      in the region of exon 6 of the Orc6 gene. Site tests revealed a proportion of
      codon sites that displayed evidence of positive selection (omega > 1) within the
      coding sequences of the vertebrate Orc6 gene. Seven positively selected amino
      acid sites were identified and three were located in exon6. These results suggest
      that amino acid residues present in the middle region of the protein are more
      selectively constrained, whereas amino acid residues in the C-terminal peptide of
      the protein evolve at a faster rate, possibly because of heightened selective
      pressure during the course of evolution.

PMID- 24122248
TI  - Osteoprotegerin and fractures in men and women with chronic  kidney disease.
AB  - Fractures are common in men and women with chronic kidney disease (CKD) but the
      best tool to identify those at high risk is unknown. Increased circulating
      osteoprotegerin(OPG) is associated with fractures in postmenopausal women. We
      determined if serum OPG was associated with prevalent fractures (self-reported
      low trauma fractures since 40 years of age and/or prevalent vertebral fractures
      identified by radiographs) in men (n = 97) and women (n = 67) with stage 3-5 CKD.
      Analyses were performed unadjusted and adjusted for stage of CKD. Results are
      expressed as mean +/- standard deviation(SD), and as odds ratio (OR) per SD
      increase in OPG with 95 % confidence intervals (CI). The mean age was 62.7 +/-
      16.3 years, and mean weight was 78.9 +/- 18.7 kg. Compared to those without
      fractures, those with fractures(n = 55) were older (p < 0.01). Serum OPG
      increased as kidney function decreased, and OPG was higher in those with
      fractures compared to those without (9.42 +/- 4.08 vs 8.06 +/- 3.11 pmol/L, p =
      0.02). After adjusting for stage of CKD, increased OPG was associated with an
      increased fracture risk (OR 1.13, 95 % CI 1.02-1.25); however, OPG did not
      discriminate fracture status well (area under the receiver operating
      characteristic curve 0.61, 95 % CI 0.52-0.70). OPG is associated with fractures
      in men and women with stage 3-5 CKD; however, the ability of OPG to discriminate
      fracture status is poor and cannot be used in isolation to assess fracture risk.
      Further studies should examine the ability of OPG in combination with other risk
      factors to better discriminate fracture status in men and women with CKD.

PMID- 24122249
TI  - Palliative treatment of bone metastases with samarium-153  EDTMP at onset of
      pain.
AB  - We evaluated the pain response and daily discomfort in patients suffering from a
      borderline degree of bone pain due to breast or lung cancer bone metastases, who
      had undergone early palliative radionuclide treatment. The results were compared
      with those from patients who had received standard analgesic therapy. Twenty-one
      patients (65.7 +/- 3 years; 17 women) with metastatic bone cancer underwent
      samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP)
      administration (group A) and 18 patients (64.3 +/- 8 years; 16 women)continued to
      receive standard analgesics (group B; control group). The patients kept a daily
      pain diary assessing both their discomfort and the pain at specific sites by
      means of a visual analog scale, rating from 0 (no discomfort-no pain)to 10 (worst
      discomfort-pain). These diaries were reviewed weekly for 2 months and three
      physicians rated the pain response on a scale from -2 (considerable
      deterioration) to +2 (considerable improvement). Baseline characteristics were
      similar in both groups. The reduction of total discomfort and of bone pain in
      group A was significantly greater compared to group B (p < 0.0001). A significant
      improvement of clinical conditions was observed in group A, where the physician
      rate changed from -1 to 1, compared to group B in which the rate changed from -1
      to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from
      breast and lung cancer in advance, i.e.,before the establishment of severe pain
      syndrome.

PMID- 24122250
TI  - High prevalence of spine-femur bone mineral density discordance  and comparison
      of vertebral fracture risk assessment using  femoral neck and lumbar spine bone
      density in Korean patients.
AB  - The aim of this study was to evaluate the prevalence of spine-femur discordance,
      and to compare the effectiveness of femoral neck (FN) and lumbar spine (LS) bone
      mineral density (BMD) for estimation of the risk of vertebral fractures. Women
      who were evaluated with dual energy X-ray absorptiometry between January 2001 and
      December 2005 were enrolled in this study. Vertebral fracture risk was calculated
      using initial FN and LS BMD. The follow-up vertebral X-rays from all subjects
      were reviewed, and the calculated estimated risk using the Fracture Risk
      Assessment Tool (FRAX((r))) was compared with the actual prevalence of vertebral
      fractures during the follow-up period. Among a total of 443 women with a mean age
      of 58.5 years, 130 women (29.3 %) demonstrated femur-spine discordance (i.e., a
      difference between FN and LS BMD of [1 SD). Most subjects having discordance
      showed lower LS BMD (73.1 %) compared to FN BMD. During the mean 7-year follow-up
      period, 12 (2.7 %) vertebral fractures occurred. In cases with high estimated
      fracture risk ([20 % for estimated fracture risk), using LSBMD significantly
      reflected the actual vertebral fracture in total subjects [odds ratio (OR) 19.29,
      95 % confidence interval (CI) 4.21-88.46], in subjects with spine-femur
      discordance (OR 16.00, 95 % CI 1.91-134.16), and in subjects with spine-femur
      discordance having lower LSBMD (OR 20.67, 95 % CI 1.63-262.71). In comparison,
      the estimated risk using FN BMD did not reflect the actual occurrence of
      vertebral fractures. In conclusion, a significant number of Korean subjects
      exhibited spine-femur discordance, and LS BMD might be more appropriate for
      estimation of vertebral fracture risk.

PMID- 24122251
TI  - IL-6 negatively regulates osteoblast differentiation through  the SHP2/MEK2 and
      SHP2/Akt2 pathways in vitro.
AB  - It has been suggested that interleukin-6 (IL-6)plays a key role in the
      pathogenesis of rheumatoid arthritis(RA), including osteoporosis not only in
      inflamed joints but also in the whole body. However, previous in vitro studies
      regarding the effects of IL-6 on osteoblast differentiation are inconsistent. The
      aim of this study was to examine the effects and signal transduction of IL-6 on
      osteoblast differentiation in MC3T3-E1 cells and primary murine calvarial
      osteoblasts. IL-6 and its soluble receptor significantly reduced alkaline
      phosphatase (ALP) activity, the expression of osteoblastic genes (Runx2, osterix,
      and osteocalcin), and mineralization in a dose-dependent manner, which indicates
      negative effects of IL-6 on osteoblast differentiation. Signal transduction
      studies demonstrated that IL-6 activated not only two major signaling pathways,
      SHP2/MEK/ERK and JAK/STAT3, but also the SHP2/PI3K/Akt2 signaling pathway. The
      negative effect of IL-6 on osteoblast differentiation was restored by inhibition
      of MEK as well as PI3K, while it was enhanced by inhibition of STAT3. Knockdown
      of MEK2 and Akt2 transfected with siRNA enhanced ALP activity and gene expression
      of Runx2. These results indicate that IL-6 negatively regulates osteoblast
      differentiation through SHP2/MEK2/ERK and SHP2/PI3K/Akt2 pathways, while
      affecting it positively through JAK/STAT3. Inhibition of MEK2 and Akt2 signaling
      in osteoblasts might be of potential use in the treatment of osteoporosis in RA.

PMID- 24122252
TI  - Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary
      carcinogenesis.
AB  - We report here a detailed time course study of the individual and combined
      chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on
      multiple histologic parameters of mammary carcinogenesis. Groups of female
      Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of
      age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet
      (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats
      were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ~90% of
      control rats had palpable tumors). Our results demonstrate a major effect of Tam
      in inhibiting the development of early preneoplastic lesions. FO, while having a
      marginal protective effect of it own, enhanced the antitumor action of Tam on all
      histologic parameters of carcinogenesis, although the effects of the combination
      were not statistically different from those of Tam alone. The combination of FO
      and Tam was the only intervention that induced regression of established
      preneoplastic lesions. We also found that in contrast to plasma, only target
      tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of
      carcinogenesis whose expression was altered in a manner predictive of a
      protective effect. Our results demonstrating the potentially superior
      chemopreventive efficacy of Tam and n-3FA have important translational
      implications. Our data also emphasize the importance of local factors in
      affecting target tissue levels and biologic effects of n-3FA.

PMID- 24122253
TI  - Retrospective review of extra-pulmonary small cell carcinoma and prognostic
      factors.
AB  - BACKGROUND: Extra-pulmonary small cell carcinoma (EPSCC) is a rare cause of
      malignancy, representing 2.5-5 % of all small cell carcinomas, with an incidence
      rate of 1000 cases per year in the USA. The purpose of this study is to
      characterize the location, extent of disease, and survival of patients with
      EPSCC, and to analyze potential clinical prognostic indicators predicting
      survival. METHODS: A retrospective review of all patients with EPSCC between the
      years 2000 and 2010 was conducted. Patients included for analysis had pathologic
      diagnosis of EPSCC, poorly differentiated tumors, and negative chest imaging at
      diagnosis. RESULTS: 53 patients were included in the analysis. 23 patients (43 %)
      had limited disease (LD) at diagnosis, and 30 patients (57 %) had extensive
      disease (ED) at diagnosis. Carcinoma of unknown primary represented the largest
      proportion of patients (40 %), followed by genitourinary (26 %), gastrointestinal
      (15 %), head and neck (11 %), gynecologic (6 %), and breast (2 %). The median
      overall survival (OS) was 4.7 months; 14.5 months for LD, and 3.7 months for ED.
      Genitourinary EPSCC had the best median OS at 13.1 months, and GI carcinomas had
      the worst at 1.7 months. On univariate analysis, ED (p = 0.0001), non
      genitourinary EPSCC (p = 0.036), and hyponatremia were associated with worse OS
      (p = 0.0176). CONCLUSIONS: In a cohort of patients with EPSCC, hyponatremia, non
      genitourinary EPSCC, and extensive disease were associated with worse OS.
      Anatomic site predicted survival, which suggests that pathologic heterogeneity
      between individual tumor sites, including mixed tumor pathology, may affect the
      prognosis of this rare disease. Future directions for research should include
      thorough pathologic and genetic profiles.

PMID- 24122254
TI  - The expression of LC-3 is related to tumor suppression through angiogenesis in
      esophageal cancer.
AB  - Autophagy is important in the development and remodeling of cells. It is required
      for cellular adaptation to nutrient deprivation and elimination of damaged
      organelles. Recently, autophagy has been implicated in carcinogenesis and
      metastasis. We hypothesized that autophagy-related proteins are initiated until
      nutrition is supplied by angiogenesis. We evaluated the clinicopathological
      significance of LC3, an autophagic marker, and its relationship to angiogenesis
      in patients with esophageal squamous cell carcinoma (ESCC). We
      immunohistochemically investigated the expression of LC3 as well as endoglin
      (CD105), a microvessel marker, and vascular endothelial growth factor A (VEGF-A)
      in 142 patients with ESCC. The high, moderate, and low expression rates of LC3
      were 40, 31, and 29 %. LC3 expression inversely correlated with depth of
      invasion, lymph node metastasis, lymphatic invasion, MVD, VEGF-A expression, and
      poor prognosis. The overall survival rate was better in patients with high LC3
      expression compared to patients with low LC3 expression. We demonstrate that low
      LC3 expression is related to tumor development as facilitated by angiogenesis and
      that alteration in LC3 expression is closely related to prognosis. Expression of
      LC3 proteins is a useful marker for determining tumor prognostic behavior in
      patients with ESCC. 

PMID- 24122255
TI  - Sequential use of mammalian target of rapamycin inhibitors in patients with
      metastatic renal cell carcinoma following failure of tyrosine kinase inhibitors.
AB  - The aim of the study is to evaluate the clinical experience of the sequential use
      of mammalian target of rapamycin inhibitors (mTORIs) for metastatic renal cell
      carcinoma (mRCC) refractory to tyrosine kinase inhibitors (TKIs). This study
      retrospectively investigated the clinical outcomes in a total of 83 consecutive
      Japanese patients with mRCC who were treated with either everolimus or
      temsirolimus following the failure of sorafenib and/or sunitinib. Of the 83
      patients, 15, 61, and 7 were classified into favorable-, intermediate-, and poor
      risk groups, respectively, according to the Memorial Sloan-Kettering Cancer
      Center model, and 47 and 36 patients were administered mTORIs as second- and
      third-line therapy, respectively. As the best responses to mTORIs, 6, 53, and 24
      were judged to have a partial response, stable disease, and progressive disease,
      respectively. The median progression-free survival (PFS) and overall survival
      (OS) of these patients following the introduction of mTORIs were 5.8 and 20.4
      months, respectively. Of the several factors examined, liver metastasis and
      pretreatment C-reactive protein (CRP) level were shown to be independently
      associated with PFS, while only pretreatment CRP level had an independent impact
      on OS. Adverse events related to mTORIs corresponding to >=grade 3 were observed
      in 26 patients, including anemia in 7, pneumonitis in 7, neutropenia in 4, and
      stomatitis in 3. Despite the low response rate, mTORIs are well tolerated and
      could provide comparatively favorable prognostic outcomes in Japanese patients
      with mRCC after the failure of TKIs.

PMID- 24122256
TI  - Phase II trial of second-line chemotherapy with docetaxel and capecitabine in
      advanced esophageal squamous cell carcinoma.
AB  - We performed a phase II trial of docetaxel in combination with capecitabine to
      evaluate the antitumor response, toxicity, and survival in pre-treated patients
      with advanced esophageal squamous cell carcinoma. Patients with advanced
      esophageal squamous cell carcinoma who had failed first-line chemotherapy with
      cisplatin and 5-fluorouracil were enrolled in this study. Treatment consisted of
      oral capecitabine (825 mg/m(2) twice daily on days 1-14) plus 1-h intravenous
      docetaxel (60 mg/m(2) on day 1) every 3 weeks for up to 6 cycles. Between June
      2008 and August 2011, thirty eligible patients with a median age of 58 years
      (range 38-68 years) were enrolled. Patients received a median of three cycles of
      treatment (range 1-6). The median follow-up was 15.4 months (range 1.0-31.5
      months). Intent-to-treat efficacy analysis demonstrated an overall response rate
      of 23.3% (0 complete response and 7 partial response) and stable disease of 43.4
      % (n = 13). The median time to progression was 3.0 months (95% CI 1.9-4.1
      months). The median survival was 8.3 months (95% CI 6.8-9.8 months). Severe
      adverse events (grade 3/4) reported were as follows: neutropenia (33.3%, n = 10,
      including febrile neutropenia 6.7%, n = 2), anemia (16.7%, n = 5),
      thrombocytopenia (10 %, n = 3), hand-foot syndrome (13.3%, n = 4), and fatigue
      (10%, n = 3). Docetaxel plus capecitabine had a manageable adverse event profile
      and promising activity in advance esophageal squamous cell carcinoma as a second
      line treatment.

PMID- 24122257
TI  - S-1 plus CIK as second-line treatment for advanced pancreatic cancer.
AB  - This study aimed to evaluate the efficacy and tolerability of S-1 (Tegafur,
      Gimeracil, and Oteracil Potassium Capsules) plus CIK (Cytokine-induced killer
      cells) in patients with advanced pancreatic cancer who had previously received
      gemcitabine-based therapy. In this prospective study, fifty-eight patients were
      randomly divided into two groups. One group (CT group) was given S-1 alone, and
      the other group (immuno-CT group) was given S-1 plus CIK. S-1 was administered
      orally twice a day at 80 mg/m(2)/day on days 1-21 of a 28-day cycle till disease
      progression or unacceptable toxicity occurred. CIK was given for one cycle of 28
      days. The disease control rate for S-1 and CIK was 40.0 and 53.6%, respectively
      (p = 0.621). The serum CA19-9 level decreased for more than 25% was significantly
      different (33.3 and 60.7 % in CT group and immuno-CT group, respectively, p =
      0.037). The median time to progression was 2.5 (95% CI 2.3-2.8) and 2.9 (95% CI
      2.6-3.2) months (p = 0.037) for CT group and immuno-CT group, respectively. The
      median overall survival was 6.1 (95% CI 5.7-6.5) and 6.6 (95% CI 6.1-7.1) months
      (p = 0.09) for CT group and immuno-CT group, respectively. The difference in
      hematological toxicity, including leukocytopenia, anemia, and neutropenia, was
      insignificant between the two groups. In contrast, the differences in non
      hematological toxicity, fatigue, and non-infective fever were significantly
      different between the two groups (p < 0.05). The S-1 plus CIK regimen was well
      tolerated in a second-line setting in patients with gemcitabine-refractory and
      advanced pancreatic cancer.

PMID- 24122258
TI  - Impact of obesity on development and progression of mammary tumors in preclinical
      models of breast cancer.
AB  - Overweight and/or obesity are known risk factors for postmenopausal breast
      cancer. More recently increased body weight has also been associated with poor
      prognosis for premenopausal breast cancer. This relationship has primarily been
      identified through epidemiological studies. Additional information from in vitro
      studies has also been produced in attempts to delineate mechanisms of action for
      the association of obesity and body weight and breast cancer. This approach has
      identified potential growth factors such as insulin, leptin, estrogen and IGF-I
      which are reported to be modulated by body weight changes. However, in vitro
      studies are limited in scope and frequently use non-physiological concentrations
      of growth factors, while long follow-up is needed for human studies. Preclinical
      animal models provide an intermediary approach to investigate the impact of body
      weight and potential growth factors on mammary/breast tumor development and
      progression. Here results of a number of studies addressing this issue are
      presented. In the majority of the studies either genetically-obese or diet
      induced obese rodent models have been used to investigate spontaneous, transgenic
      and carcinogen-induced mammary tumor development. To study tumor progression the
      major focus has been allograft studies in mice with either genetic or dietary
      induced obesity. In general, obesity has been demonstrated to shorten mammary
      tumor latency and to impact tumor pathology. However, in rodents with defects in
      leptin and other growth factors the impact of obesity is not as straightforward.
      Future studies using more physiologically relevant obesity models and clearly
      distinguishing diet composition from body weight effects will be important in
      continuing to understand the factors associated with body weight's impact on
      mammary/breast cancer development and progression.

PMID- 24122259
TI  - Does graft mass impact on pediatric kidney transplant outcomes?
AB  - BACKGROUND: The aim of this study is to assess the evolution of renal size and
      function in pediatric transplant patients according to the graft mass/recipient
      size ratio. METHODS: Fifty pediatric renal transplant recipients were followed
      over 2 years. Grafts were weighed, and three different graft mass/m(2) ratios
      were determined: (1) low graft mass (58 g/m(2), range 31-57 g/m(2)), (2) median
      (142 g/m(2), range 59-141 g/m(2)) and high (267 g/m(2), range 143-353 g/m(2)).
      Patients underwent repeated ultrasound Doppler scans and repeated measurements of
      estimated glomerular filtration rate (eGFR; 1 week and 1, 6, 12 and 24 months),
      urinary retinol-binding protein (RBP) and proteinuria (1 week and 6, 12 and 24
      months). RESULTS: The volume of renal tissue increased by 12 +/- 5.6 cm(3) at 24
      months (p = 0.035) in the low graft mass and decreased by -14 +/- 7 cm(3) (p =
      0.046) in the high graft mass. The eGFR increased when either low (30 +/- 5
      ml/min/1.73 m(2), p < 0.001) or median (19 +/- 4 ml/min/1.73 m(2), p < 0.001)
      graft mass was transplanted but remained stable when high graft mass was
      transplanted. The resistive index (RI) presented a significant decrease
      throughout early follow-up in the transplants involving low and median graft
      mass, whereas a slight rise was observed in those involving high graft mass. A
      significant difference was apparent 6 months post-transplant. Transplants of low
      and median graft mass were associated with an initial higher urinary RBP. No
      significant differences in proteinuria were detected. CONCLUSIONS: Small kidneys
      undergo increases in volume and function without escalation of either proteinuria
      or urinary RBP, characterizing an adequate adaptation to the recipient. Children
      receiving larger kidneys present a reduction in volume, stable GFR and higher RI
      at 6 months.

PMID- 24122260
TI  - A biphasic dialytic strategy for the treatment of neonatal hyperammonemia.
AB  - BACKGROUND: Neonates with inborn errors of metabolism (IEM) often develop
      hyperammonemia which, if not corrected quickly, may result in poor neurologic
      outcomes. As pharmacologic therapy cannot rapidly lower ammonia levels, dialysis
      is frequently required. Both hemodialysis (HD) and standard-dose continuous renal
      replacement therapy (CRRT) are effective; however, HD may be followed by post
      dialytic ammonia rebound, and standard-dose CRRT may not effect a rapid enough
      decrease in ammonia levels. CASE-DIAGNOSIS/TREATMENT: We present two cases of IEM
      associated neonatal hyperammonemia in which we employed a biphasic, high-dose
      CRRT treatment strategy, initially using dialysate flow rates of 5,000 mL/h
      (approximately 40,000 mL/h/1.73 m(2)) in order to rapidly decrease ammonia
      levels, then decreasing the dialysate flow rates to 500 mL/h (approximately 4,000
      mL/h/1.73 m(2)) in order to prevent ammonia rebound. CONCLUSIONS: This biphasic
      dialytic treatment strategy for neonatal hyperammonemia effected rapid ammonia
      reduction without rebound and accomplished during a single dialysis run without
      equipment changes.

PMID- 24122261
TI  - The therapeutic effects of anti-oxidant and anti-inflammatory drug quercetin on
      aspiration-induced lung injury in rats.
AB  - Aspiration pneumonitis refers to acute chemical lung injury caused by aspiration
      of sterile gastric contents. The aim of this study was to evaluate the role of
      quercetin (QC) in acid aspiration-induced lung injury in rats. Twenty-eight
      female Sprague-Dawley rats were used and divided into the following groups (n =
      7): sham (aspirated normal saline, S), hydrochloric acid (aspirated HCl), S plus
      treatment with QC (S + QC), and HCl plus treatment with QC (HCl + QC). After
      aspiration, the treatment groups received QC 60 mg/kg/day intraperitoneally once
      a day for 7 days. As a result of acid aspiration, an increase was observed in the
      levels of serum clara cell protein-16 (CC-16) and advanced oxidation protein
      products, whereas there was a decrease in serum thiobarbituric acid-reactive
      substances, superoxide dismutase (SOD), and catalase levels. There was a
      significant decrease in peribronchial inflammatory cell infiltration, alveolar
      septal infiltration, alveolar edema, and alveolar exudate scores, except in the
      alveolar histiocytes in the HCl + QC group. The expression of nitric oxide
      synthase, which increased after aspiration in the HCl group, showed a
      statistically significant decrease after the QC treatment. After the treatment
      with QC, an increase in the serum SOD level was observed, whereas a significant
      decrease was determined in the serum CC-16 level relative to that of the
      aspiration group (HCl). The antioxidant QC is effective in the treatment of lung
      injury following acid aspiration and can be used as a serum CC-16 biomarker in
      predicting the severity of oxidative lung injury.

PMID- 24122263
TI  - Metastatic progression of breast cancer: insights from 50 years of autopsies.
AB  - There remain no clear guidelines for the optimal management of patients with
      metastatic breast cancer. To better understand its natural history, we undertook
      a detailed examination of 197 autopsies performed on women who died of breast
      cancer. We reviewed clinical, treatment and pathological aspects of all cases
      and, additionally, pathological features and biomarker expression (ER, PgR, HER2,
      EGFR, p53, Ki67, c-Kit, CK AE1/AE3) were assessed in detail for the primary
      tumour and matched metastases for 55 of the cases. Genomes of the primary tumour
      and multiple metastases were analysed by array-based comparative genomic
      hybridization for six cases(##) . 945 metastatic deposits were identified, with a
      median of four/patient. The most common organs involved were lung/pleura (80%),
      bone (74%), liver (71%) and non-axillary lymph nodes (55%). Major findings
      included: (a) patients with CNS metastases were more likely to have bone
      metastases (p < 0.013); (b) younger age was associated with metastasis to the
      liver (<= 49 years; p < 0.001) and to gynaecological organs (<= 49 years; p =
      0.001); (c) surgical excision of the primary tumour was associated with
      metastasis to the liver (p = 0.002); and (d) ER and PgR showed down-regulation
      during progression in a non-random manner, particularly in lung/pleura (ER; p <
      0.001), liver and bone metastases. Genomic analysis revealed DNA copy number
      variation between the primary tumour and metastases (e.g. amplification of 2q11.2
      q12.1 and 10q22.2-q22.3) but little variation between metastases from the same
      patient. In summary, the association of CNS and bone metastases, liver and
      gynaecological metastases in young women and the risk of liver metastases
      following surgery have important implications for the management of patients with
      breast cancer. Clonal heterogeneity of the primary tumour is important in
      developing metastatic propensity and the change in tumour phenotype during
      progression/colonization highlights the importance of sampling metastatic disease
      for optimal treatment strategies.

PMID- 24122264
TI  - Protective effects of curcumin against rotenone and salsolinol-induced toxicity:
      implications for Parkinson's disease.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative disorder that
      results from the loss of or damage to dopaminergic cells in the substantia nigra.
      Exposure to either the pesticide rotenone or the endogenous neurotoxin salsolinol
      has been shown to mimic this dopaminergic cell loss. In this study, we first
      sought to determine whether combination of rotenone and salsolinol would result
      in an additive or synergistic toxicity. For this purpose we utilized SH-SY5Y
      cells, a human neuroblastoma cell line that is commonly used to model
      dopaminergic neurodegeneration. We then tested whether curcumin, a natural plant
      compound with known health benefits including potential neuroprotective
      properties, could also protect against rotenone and/or salsolinol-induced
      toxicity. Moreover, since apoptotic mechanism has been implicated in toxicity of
      these compounds the anti-apoptotic effect of curcumin was also evaluated. Our
      results indicate a synergistic toxicity of low concentrations of rotenone (1 and
      5 uM) and salsolinol (25 and 50 uM) that was associated with apoptosis as
      determined by cell flow cytometry. There was also an increase in caspase-3
      levels. Pretreatment with curcumin (1-uM) dose-dependently attenuated rotenone
      and/or salsolinol-induced toxicity and the associated apoptosis. These results
      suggest that exposure to a combination of rotenone and salsolinol may contribute
      to the pathology of PD, and that curcumin has a therapeutic potential in this
      disease.

PMID- 24122265
TI  - Effects of bromide and iodide ions on the formation of disinfection by-products
      during ozonation and subsequent chlorination of water containing biological
      source matters.
AB  - This study aims to investigate the influence of the coexistence of halogen ions
      (bromide/iodide) and biological source matters on the speciation and yield of
      trihalomethanes (THMs), haloacetic acids (HAAs), and N-nitrosodimethylamine
      (NDMA) during the ozonation and subsequent chlorination of water. The results
      show that the concentrations of brominated THMs and iodinated THMs increased with
      increasing bromide and iodide concentration. These results may be attributed to
      the higher reactivity of hypobromous acid and hypoiodous acid generated from the
      ozonation and subsequent chlorination in the presence of bromide or iodide ions.
      The presence of bromide increased the species of brominated HAAs. There was a
      shift from chlorinated HAAs to brominated HAAs after increasing the concentration
      of bromide. The effect of iodide on HAA formation was more complex than bromide.
      For most samples, the concentration of total HAAs (T-HAAs) increased to the
      maximum and then decreased with increasing iodide concentration. The components
      of the organic precursors also significantly influenced the formation of
      brominated and iodinated disinfection by-products (Br-DBPs and I-DBPs). Humic
      acids produced more CHBr3 (596.60 MUg/L) than other organic materials.
      Microcystis aeruginosa cells produced the most tribromoacetic acid (TBAA, 84.16
      MUg/L). Furthermore, the yield of NDMA decreased with increasing bromide
      concentration, indicating that the formation of NDMA was inhibited by the high
      concentration of bromide.

PMID- 24122266
TI  - Issues to consider in the derivation of water quality benchmarks for the
      protection of aquatic life.
AB  - While water quality benchmarks for the protection of aquatic life have been in
      use in some jurisdictions for several decades (USA, Canada, several European
      countries), more and more countries are now setting up their own national water
      quality benchmark development programs. In doing so, they either adopt an
      existing method from another jurisdiction, update on an existing approach, or
      develop their own new derivation method. Each approach has its own advantages and
      disadvantages, and many issues have to be addressed when setting up a water
      quality benchmark development program or when deriving a water quality benchmark.
      Each of these tasks requires a special expertise. They may seem simple, but are
      complex in their details. The intention of this paper was to provide some
      guidance for this process of water quality benchmark development on the program
      level, for the derivation methodology development, and in the actual benchmark
      derivation step, as well as to point out some issues (notably the inclusion of
      adapted populations and cryptic species and points to consider in the use of the
      species sensitivity distribution approach) and future opportunities (an
      international data repository and international collaboration in water quality
      benchmark development).

PMID- 24122267
TI  - Toxicity of five antidepressant drugs on embryo-larval development and
      metamorphosis success in the Pacific oyster, Crassostrea gigas.
AB  - Unlike conventional pollutants, pharmaceutical residues are continuously
      discharged at low levels (low to mid ng l(-1) concentrations), which results in
      the chronic contamination of non-target organisms, but little is known about the
      effects of these residues. The purpose of this study was to provide the first
      assessment of the ecotoxicity of five antidepressants (selective serotonin
      reuptake inhibitors [SSRIs] fluoxetine and sertraline, tricyclic antidepressants
      [TCAs] clomipramine and amitriptyline, and serotonin norepinephrine reuptake
      inhibitor [SNRI] duloxetine) at a wide range of concentrations from 0.1 to
      100,000 MUg l(-1) on two early life stages in the Pacific oyster. The toxicity
      was quantified in D-shaped larvae after 36 h of exposure, and in 21-day-old
      pediveliger larvae after 24 h of exposure using the percentage of normal larval
      development and the metamorphosis rate as endpoints, respectively. The
      embryotoxicity assays reported that the EC50 values were within the same range of
      concentrations (67 to 192 MUg l(-1)) for all of the tested molecules. The
      metamorphosis tests revealed that the antidepressants can be ranked along an
      increasing severity gradient: clomipramine < amitriptyline < duloxetine ~
      fluoxetine. Sertraline appeared to be the less toxic molecule on this endpoint;
      however, a different concentration range was used. The embryotoxicity test was
      more sensitive than the metamorphosis bioassay for three of the five molecules
      tested, but the latter test showed more practical benefits. Overall, the obtained
      toxicity values were at least 10,000-fold higher than the reported environmental
      concentrations.

PMID- 24122268
TI  - Isolation and characterization of a newly isolated pyrene-degrading Acinetobacter
      strain USTB-X.
AB  - The pryene-degradation bacterium strain USTB-X was newly isolated from the
      polycyclic aromatic hydrocarbon (PAH)-contaminated soil in Beijing Coking Plant,
      China. The strain was identified as Acinetobacter with respect to its 16S rDNA
      and morphological and physiological characteristics. The strain was Gram
      negative, non-mobile, non-acid-fast, and non-spore-forming, short rods in young
      culture and 0.8-1.6 MUm in diameter and 1.2-2.5 MUm long in the stationary phase
      of growth. Strain USTB-X could utilize pyrene, naphthalene, fluorene,
      phenanthrene, benzene, toluene, ethylbenzene, ethanol, methanol, and Tween 80 as
      sole source of carbon and energy. The strain could produce biosurfactants which
      enhanced the removal of pyrene and could remove 63 % of pyrene with an initial
      concentration of 100 mg.L-1 in 16 days without other substrates. Based on the
      intermediates analyzed by gas chromatography-mass spectrometry, we also deduced
      the possible metabolic pathway of strain USTBX for pyrene biodegradation. Results
      indicated that the strain USTB-X had high potential to enhance the removal of
      PAHs in contaminated sites.

PMID- 24122269
TI  - A laboratory-incubated redox oscillation experiment to investigate Hg fluxes from
      highly contaminated coastal marine sediments (Gulf of Trieste, Northern Adriatic
      Sea).
AB  - Mercury (Hg) mobility at the sediment-water interface was investigated during a
      laboratory incubation experiment conducted with highly contaminated sediments (13
      MUg g(-1)) of the Gulf of Trieste. Undisturbed sediment was collected in front of
      the Isonzo River mouth, which inflows Hg-rich suspended material originating from
      the Idrija (NW Slovenia) mining district. Since hypoxic and anoxic conditions at
      the bottom are frequently observed and can influence the Hg biogeochemical
      behavior, a redox oscillation was simulated in the laboratory, at in situ
      temperature, using a dark flux chamber. Temporal variations of several parameters
      were monitored simultaneously: dissolved Hg (DHg) and methylmercury (MeHg), O2,
      NH4 (+), NO3 (-) + NO2 (-), PO4 (3-), H2S, dissolved Mn(2+), dissolved inorganic
      and organic carbon (DIC and DOC). Under anoxic conditions, both Hg (665 ng m(2)
      day(-1)) and MeHg (550 ng m(2) day(-1)) fluxed from sediments into the water
      column, whereas re-oxygenation caused concentrations of MeHg and Hg to rapidly
      drop, probably due to re-adsorption onto Fe/Mn-oxyhydroxides and enhanced
      demethylation processes. Hence, during anoxic events, sediments of the Gulf of
      Trieste may be considered as an important source of DHg species for the water
      column. On the contrary, re-oxygenation of the bottom compartment mitigates Hg
      and MeHg release from the sediment, thus acting as a natural "defence" from
      possible interaction between the metal and the aquatic organisms.

PMID- 24122270
TI  - Inhibitory effect of cyanide on nitrification process and its eliminating method
      in a suspended activated sludge process.
AB  - Inhibition of nitrification by four typical pollutants (acrylonitrile, acrylic
      acid, acetonitrile and cyanide) in acrylonitrile wastewater was investigated. The
      inhibitory effect of cyanide on nitrification was strongest, with a 50%
      inhibitory concentration of 0.218 mg.gVSS-1 being observed in a municipal
      activated sludge system. However, the performance of nitrification was recovered
      when cyanide was completely degraded. The nitrification, which had been inhibited
      by 4.17 mg.gVSS-1 of free cyanide for 24 h, was recovered to greater than 95% of
      that without cyanide after 10 days of recovery. To overcome cyanide inhibition,
      cyanide-degrading bacteria were cultivated in a batch reactor by increasing the
      influent cyanide concentration in a stepwise manner, which resulted in an
      increase in the average cyanide degradation rate from 0.14 to 1.01 mg CN-.gVSS
      1.h-1 over 20 days. The cultured cyanide-degrading bacteria were shaped like
      short rods, and the dominant cyanide-degrading bacteria strain was identified as
      Pseudomonas fluorescens NCIMB by PCR.

PMID- 24122271
TI  - The elevated pre-operative plasma fibrinogen level is an independent negative
      prognostic factor for cancer-specific, disease-free and overall survival in soft
      tissue sarcoma patients.
AB  - BACKGROUND AND OBJECTIVES: Accumulating evidence indicates an important
      pathophysiological role of fibrinogen on tumor cell progression and metastases in
      different types of cancer. The aim of the present study was to evaluate the
      prognostic relevance of pre-operative fibrinogen levels on clinical outcome in a
      large cohort of STS patients. METHODS: Two hundred ninety-four consecutive STS
      patients were retrospectively evaluated. Cancer-specific survival (CSS), disease
      free survival (DFS), and overall survival (OS) were assessed using the Kaplan
      Meier curves and Cox regression models. Finally, we supplemented the well
      established Kattan nomogram by the fibrinogen level and evaluated the gain of
      predictive accuracy of this novel nomogram by Harrell's concordance index (c
      index). RESULTS: An elevated plasma fibrinogen level was significantly associated
      with established prognostic factors, including age, tumor grade, size, and depth
      (P<0.05). Furthermore, in multivariate analysis, increased fibrinogen levels were
      significantly associated with a poor outcome for CSS (HR=2.48; 95% CI=1.28-4.78;
      P=0.007), DFS (HR=2.00; 95% CI=1.11-3.60; P=0.021), and OS (HR=2.20; 95% CI=1.39
      3.47; P<0.001). The estimated c-index was 0.747 using the original Kattan
      nomogram and 0.779 when the fibrinogen levels was added. CONCLUSION: The pre
      operative plasma fibrinogen level may represent a strong and independent
      unfavorable prognostic factor for CSS, DFS and OS in STS patients.

PMID- 24122272
TI  - Characterization of pituitary cells targeted by antipituitary antibodies in
      patients with isolated autoimmune diseases without pituitary insufficiency may
      help to foresee the kind of future hypopituitarism.
AB  - PURPOSE: Detection of antipituitary antibodies (APA) at high levels and with a
      particular immunofluorescence pattern in patients with autoimmune polyendocrine
      syndromes may indicate a possible future autoimmune pituitary involvement. This
      longitudinal study was aimed at characterizing in patients with a single organ
      specific autoimmune disease the pituitary cells targeted by APA at start,
      verifying whether this characterization allows to foresee the kind of possible
      subsequent hypopituitarism. METHODS: Thirty-six APA positive and 40 APA negative
      patients with isolated autoimmune diseases participated in the study. None of
      them had pituitary dysfunction at entry. Characterization by four-layer
      immunofluorescence of pituitary cells targeted by APA in APA positive patients at
      entry and study of pituitary function in all patients were performed every 6
      months during a 5 year follow-up. RESULTS: Antipituitary antibodies immunostained
      selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group
      1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2).
      All patients in group 1 showed subsequently a pituitary insufficiency,
      corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8
      out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7
      and combined in the other one. None of APA negative patients showed
      hypopituitarism. CONCLUSIONS: The characterization of pituitary cells targeted by
      APA in patients with isolated autoimmune diseases, when the pituitary function is
      still normal, may help to foresee the kind of subsequent hypopituitarism,
      especially when APA immunostained selectively only one type of pituitary cells. A
      careful follow-up of pituitary function in these patients is advisable to allow
      an early diagnosis of hypopituitarism, even in subclinical phase and a consequent
      timely replacement therapy.

PMID- 24122273
TI  - RNA polymerase II CTD modifications: how many tales from a single tail.
AB  - Eukaryote's RNA polymerases II (RNAPII) have the feature to contain, at the
      carbossi-terminal region of their largest subunit Rpb1, a unique CTD domain. Rpb1
      CTD is composed of an increasing number of repetitions of the Y1 S2 P3 T4 S5 P6
      S7 heptad that goes in parallel with the developmental level of organisms.
      Because of its composition, the CTD domain has a huge structural plasticity;
      virtually all the residues can be subjected to post-translational modifications
      and the two prolines can either be in cis or trans conformations. In light of
      these features, it is reasonable to think that different specific nuances of CTD
      modification and interacting factors take place not only on different gene
      promoters but also during different stages of the transcription cycle and
      reasonably might have a role even if the polymerase is on or off the DNA
      template. Rpb1-CTD domain is involved not only in regulating transcriptional
      rates, but also in all co-transcriptional processes, such as pre-mRNA processing,
      splicing, cleavage, and export. Moreover, recent studies highlight a role of CTD
      in DNA replication and in maintenance of genomic stability and specific CTD
      modifications have been related to different CTD functions. In this paper, we
      examine results from the most recent CTD-related literature and give an overview
      of the general function of Rpb1-CTD in transcription, transcription-related and
      non transcription-related processes in which it has been recently shown to be
      involved in.

PMID- 24122274
TI  - Ictal electroencephalography and electromyography features in symptomatic
      infantile epileptic encephalopathy with late-onset spasms.
AB  - AIM: Recently, epilepsy with late-onset epileptic spasms (ES) has been reported
      to be distinct from West syndrome and Lennox-Gastaut syndrome. We identified the
      characteristics of this clinical entity by analyzing clinical data, including
      ictal electroencephalography (EEG) and electromyography (EMG) in symptomatic
      patients. METHODS: We evaluated retrospectively eight symptomatic patients with
      epilepsy with late-onset ES. All patients underwent video-EEG analysis for more
      than 24 hours and have been followed up for at least 1 year. Interictal EEG,
      ictal EEG, ictal EMG, coexistence seizures, response to treatment, and
      intellectual or daily activity level were assessed. Ictal EMG was evaluated by
      spectral analysis. RESULTS: All patients exhibited neurological deterioration and
      had multiple seizure types; seven of them had intractable seizures. Interictal
      EEG showed no typical hypsarrhythmia in any case. Ictal EMG analysis revealed
      that the predominant seizure types presenting with the tonic component were
      distributed among ES, spasms followed by tonic seizures (SFT), and tonic
      seizures. CONCLUSIONS: The clinical characteristics of our patients were
      identical to infantile epileptic encephalopathy with late-onset spasms. Our
      patients had ES, SFT, and tonic seizures as the core seizure types, developed ES
      beyond the age of 1 year, and showed neurological deterioration. These may be
      essential symptoms of this clinical entity.

PMID- 24122275
TI  - Reliability of fractional anisotropy measurement for children with cerebral
      palsy.
AB  - OBJECTIVE: Periventricular leukomalacia (PVL) is the leading cause of disability
      in children with cerebral palsy (CP). Diffusion tensor imaging (DTI) is a
      magnetic resonance imaging technique for detecting microstructural lesions of
      white matter. Fractional anisotropy (FA) is a widely used DTI index with clinical
      significance in children with CP. This study aims to estimate the reliability of
      FA for children with CP. DESIGN: Four observers measured FA values in 78 children
      with spastic CP from PVL. Region of interests (ROIs) were placed in three
      anatomical loci at each side: medial and lateral portions of posterior limb of
      internal capsule and ascending sensory tract. Intra- and interobserver
      reliability indices including intraclass correlation coefficient (ICC), standard
      error of measurement, smallest real difference percentage (SRD%), and limit of
      agreement using Bland-Altman analysis were examined. RESULTS: Intraobserver ICCs
      were 0.85 or greater in all ROIs, and SRD% ranged from 3.59 to 12.33%.
      Interobserver ICCs exceeded 0.90 in all ROIs, and the SRD% were less than 10%.
      The Bland-Altman analysis showed good intra- and interobserver agreements. The
      reliability was not affected by severity of impairment. CONCLUSIONS: Reliability
      of DTI-derived FA value using ROIs was satisfactory in children with PVL.

PMID- 24122276
TI  - Acoustic characterisation of liquid foams with an impedance tube.
AB  - Acoustic measurements provide convenient non-invasive means for the
      characterisation of materials. We show here for the first time how a commercial
      impedance tube can be used to provide accurate measurements of the velocity and
      attenuation of acoustic waves in liquid foams, as well as their effective
      "acoustic" density, over the 0.5-6kHz frequency range. We demonstrate this using
      two types of liquid foams: a commercial shaving foam and "home-made" foams with
      well-controlled physico-chemical and structural properties. The sound velocity in
      the latter foams is found to be independent of the bubble size distribution and
      is very well described by Wood's law. This implies that the impedance technique
      may be a convenient way to measure in situ the density of liquid foams. Important
      questions remain concerning the acoustic attenuation, which is found to be
      influenced in a currently unpredictible manner by the physico-chemical
      composition and the bubble size distribution of the characterised foams. We
      confirm differences in sound velocities in the two types of foams (having the
      same structural properties) which suggests that the physico-chemical composition
      of liquid foams has a non-negligible effect on their acoustic properties. 

PMID- 24122277
TI  - Flow patterns and deformation modes of coaxial liquid columns in transverse
      electric fields.
AB  - Steady-state flow patterns and deformation modes of coaxial liquid columns in
      transverse electric fields are studied analytically. The governing creeping flow
      equations are solved for Newtonian and (mutually) immiscible fluids in the
      framework of leaky dielectric theory. A detailed analysis of the electric and
      flow fields is presented and it is shown that there will be four possible flow
      patterns in and around the columns, in terms of the direction of the external
      flow (top-to-sides/bottom-to-sides vs. sides-to-top/sides-to-bottom) and the
      number of vortices (single vortex vs. double vortices) in the shell, and that the
      senses of the net electric shear stresses at the inner and the outer interfaces
      and their relative importance are the key parameters in setting these patterns.
      Equilibrium shapes of the interfaces are also found and it is shown that there
      are four distinct modes of deformation, depending on the governing nondimensional
      parameters of the problem. The instability of the jet is also examined
      qualitatively using the observations pertaining the instability of single-phase
      drops and jets and the scaling arguments based on the present solution. 

PMID- 24122278
TI  - Biaxial coherence length in a nematic pi-cell.
AB  - In a highly frustrated calamitic nematic phase, the strain can be relaxed by
      lowering the nematic order: the starting uniaxial symmetry can be broken and it
      can be replaced locally with transient biaxial domains. Using simple optical
      retardation measurements, we estimate the length scale over which the biaxial
      disturbance decays in space within a pi-cell submitted to a weak electric field.
      We also characterise the transition cascade from the uniaxial splay texture to a
      bend texture through slow defect motion. 

PMID- 24122280
TI  - Detective value of historical height loss and current height/knee height ratio
      for prevalent vertebral fracture in Japanese postmenopausal women.
AB  - Vertebral fracture (VFx) is associated with various co-morbidities and increased
      mortality. In this paper, we have studied the detective value of height loss for
      VFx using two indices; historical height loss (HHL) which is the difference
      between the maximal height, and the current height (CH), and CH/knee height (KH)
      ratio. One-hundred and fifty-one postmenopausal women visiting the outpatient
      clinic of orthopaedics were studied for their CH, self-reported maximal height,
      KH, and radiographically diagnosed VFx number(s). VFx was present in 41.1 % of
      the subjects. Multiple regression analyses revealed that the number of prevalent
      fractures was a significant predictor of HHL and CH/KH ratio. Receiver operator
      characteristic curve analysis has shown that for HHL, the area under the curve
      (AUC) with their 95 %CI in the parentheses was 0.84 (0.77, 0.90), 0.88 (0.83,
      0.94), and 0.91 (0.86, 0.96) for >= 1, >= 2, and >= 3 fractures, respectively.
      For the presence of >= 1 VFx, the cut-off value was 4.0 cm (specificity 79 %;
      sensitivity 79 %). Regarding the CH/KH ratio, AUC was 0.73 (0.65, 0.82), 0.85
      (0.78, 0.93), and 0.91 (0.86, 0.96) for >= 1, >= 2, and >= 3 fractures,
      respectively. For the presence of >= 1 VFx, the cut-off value was 3.3
      (specificity 47 %; sensitivity 91 %). Both cut-off values for HHL and CH/KH ratio
      had high negative predictivity across the wide range of theoretical VFx
      prevalence. Thus, HHL and CH/KH were both good detectors of VFx. Our data would
      be the basis to determine the cut-off value for the screening or case finding of
      subjects with VFx.

PMID- 24122279
TI  - Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing hTERT
      enzyme activity and disrupting F-actin organization of prostate cancer cells.
AB  - Animal and cell culture studies have showed that boron and its derivatives may be
      promising anticancer agents in prostate cancer treatment. Thus, DU145 cells were
      treated with disodium pentaborate decahydrate (DPD) for 24, 48, and 72 h in order
      to investigate the inhibitor effect and mechanisms of DPD. Then, cell
      proliferation, telomerase enzyme activity, actin polymerization, and apoptosis
      were detected by WST-1 assay, qRT-PCR, immunofluorescence labeling, and flow
      cytometry, respectively. We found that DPD inhibited the growth of human prostate
      cancer cell line DU145 at the concentration of 3.5 mM for 24 h. Our results
      demonstrated that 7 mM of DPD treatment prevented the telomerase enzyme activity
      at the rate of 38 %. Furthermore, DPD has an apoptotic effect on DU145 cells
      which were examined by labeling DNA breaks. With 7 mM of DPD treatment, 8, 14,
      and 41 % of apoptotic cells were detected for 24, 48, and 72 h, respectively.
      Additionally, immunofluorescence labeling showed that the normal organization of
      actin filaments was disrupted in DPD-exposed cells, which is accompanied by the
      alteration of cell shape and by apoptosis in targeted cells. Taken together, the
      results indicate that DPD may exert its cytotoxicity at least partly by
      interfering with the dynamic properties of actin polymerization and decreasing
      the telomerase activity. Eventually, for the first time, the results of this
      study showed that DPD suppressed the activity of telomerase in DU145 cells, and
      therefore, we suggested that DPD could be an important agent for its therapeutic
      potential in the treatment of prostate cancer.

PMID- 24122281
TI  - A high-throughput screening method to reengineer DNA polymerases for random
      mutagenesis.
AB  - A screening system for directed evolution of DNA polymerases employing a
      fluorescent Scorpion probe as a reporter has been developed. The screening system
      has been validated in a directed evolution experiment of a distributive
      polymerase from the Y-polymerase family (Dpo4 from Sulfolobus solfataricus) which
      was improved in elongation efficiency of consecutive mismatches. The engineering
      campaign yielded improved Dpo4 polymerase variants one of which was successfully
      benchmarked in a sequence saturation mutagenesis experiment especially with
      regard to the desirable consecutive transversion mutations ([2.5-fold increase in
      frequency relative to a reference library prepared with Dpo4 WT). The Scorpion
      probe screening system enables to reengineer polymerases with low processivity
      and fidelity, and no secondary activities (i.e. exonuclease activity or strand
      displacement activity) to match demands in diversity generation for directed
      protein evolution.

PMID- 24122282
TI  - Inverse PCR-based method for isolating novel SINEs from genome.
AB  - Short interspersed elements (SINEs) are moderately repetitive DNA sequences in
      eukaryotic genomes. Although eukaryotic genomes contain numerous SINEs copy, it
      is very difficult and laborious to isolate and identify them by the reported
      methods. In this study, the inverse PCR was successfully applied to isolate SINEs
      from Opsariichthys bidens genome in Eastern Asian Cyprinid. A group of SINEs
      derived from tRNA(Ala) molecular had been identified, which were named Opsar
      according to Opsariichthys. SINEs characteristics were exhibited in Opsar, which
      contained a tRNA(Ala)-derived region at the 5' end, a tRNA-unrelated region, and
      AT-rich region at the 3' end. The tRNA-derived region of Opsar shared 76 %
      sequence similarity with tRNA(Ala) gene. This result indicated that Opsar could
      derive from the inactive or pseudogene of tRNA(Ala). The reliability of method
      was tested by obtaining C-SINE, Ct-SINE, and M-SINEs from Ctenopharyngodon
      idellus, Megalobrama amblycephala, and Cyprinus carpio genomes. This method is
      simpler than the previously reported, which successfully omitted many steps, such
      as preparation of probes, construction of genomic libraries, and hybridization.

PMID- 24122283
TI  - Cloning, heterologous expression, purification and characterization of M12 mutant
      of Aspergillus niger glucose oxidase in yeast Pichia pastoris KM71H.
AB  - Aspergillus niger glucose oxidase (GOx) genes for wild-type (GenBank accession
      no. X16061, swiss-Prot; P13006) and M12 mutant (N2Y, K13E, T30 V, I94 V, K152R)
      were cloned into pPICZalphaA vector for expression in Pichia pastoris KM71H
      strain. The highest expression level of 17.5 U/mL of fermentation media was
      obtained in 0.5 % (v/v) methanol after 9 days of fermentation. The recombinant
      GOx was purified by cross-flow ultrafiltration using membranes of 30 kDa
      molecular cutoff and DEAE ion-exchange chromatography at pH 6.0. Purified wt GOx
      had k cat of 189.4 s-1 and K(m) of 28.26 mM while M12 GOx had k cat of 352.0 s-1
      and K m of 13.33 mM for glucose at pH 5.5. Specificity constants k(cat)/K(m) of
      wt (6.70 mM-1 s-1) and M12 GOx (26.7 mM-1 s-1) expressed in P. pastoris KM71H
      were around three times higher than for the same enzymes previously expressed in
      Saccharomyces cerevisiae InvSc1 strain. The pH optimum and sugar specificity of
      M12 mutant of GOx remained similar to the wild-type form of the enzyme, while
      thermostability was slightly decreased. M12 GOx expressed in P. pastoris showed
      three times higher activity compared to the wt GOx toward redox mediators like
      N,N-dimethyl-nitroso-aniline used for glucose strips manufacturing. M12 mutant of
      GOx produced in P. pastoris KM71H could be useful for manufacturing of glucose
      biosensors and biofuel cells.

PMID- 24122284
TI  - Plant promoters: an approach of structure and function.
AB  - With current advances in genomics, several technological processes have been
      generated, resulting in improvement in different segments of molecular research
      involving prokaryotic and eukaryotic systems. A widely used contribution is the
      identification of new genes and their functions, which has led to the elucidation
      of several issues concerning cell regulation and interactions. For this, increase
      in the knowledge generated from the identification of promoters becomes
      considerably relevant, especially considering that to generate new technological
      processes, such as genetically modified organisms, the availability of promoters
      that regulate the expression of new genes is still limited. Considering that this
      issue is essential for biotechnologists, this paper presents an updated review of
      promoters, from their structure to expression, and focuses on the knowledge
      already available in eukaryotic systems. Information on current promoters and
      methodologies available for studying their expression are also reported.

PMID- 24122285
TI  - Model based evaluation of a contaminant plume development under aerobic and
      anaerobic conditions in 2D bench-scale tank experiments.
AB  - The influence of transverse mixing on competitive aerobic and anaerobic
      biodegradation of a hydrocarbon plume was investigated using a two-dimensional,
      bench-scale flow-through laboratory tank experiment. In the first part of the
      experiment aerobic degradation of increasing toluene concentrations was carried
      out by the aerobic strain Pseudomonas putida F1. Successively, ethylbenzene
      (injected as a mixture of unlabeled and fully deuterium-labeled isotopologues)
      substituted toluene; nitrate was added as additional electron acceptor and the
      anaerobic denitrifying strain Aromatoleum aromaticum EbN1 was inoculated to study
      competitive degradation under aerobic /anaerobic conditions. The spatial
      distribution of anaerobic degradation was resolved by measurements of compound
      specific stable isotope fractionation induced by the anaerobic strain as well as
      compound concentrations. A fully transient numerical reactive transport model was
      employed and calibrated using measurements of electron donors, acceptors and
      isotope fractionation. The aerobic phases of the experiment were successfully
      reproduced using a double Monod kinetic growth model and assuming an initial
      homogeneous distribution of P. putida F1. Investigation of the competitive
      degradation phase shows that the observed isotopic pattern cannot be explained by
      transverse mixing driven biodegradation only, but also depends on the inoculation
      process of the anaerobic strain. Transient concentrations of electron acceptors
      and donors are well reproduced by the model, showing its ability to simulate
      transient competitive biodegradation.

PMID- 24122287
TI  - Prognostic factors in patients hospitalized for heart failure.
AB  - Each year, there are over one million hospitalizations for heart failure in the
      United States, with a similar number in Western Europe. Although these patients
      respond to initial therapies, they have very high short and intermediate term (2
      6 months) mortality and readmission rates, while the healthcare system incurs
      substantial costs. Several risk prediction models that can accurately identify
      high-risk patients have been developed using data from clinical trials, large
      registries or administrative databases. Use of multi-variable risk models at the
      time of hospital admission or discharge offers better risk stratification and
      should be encouraged, as it allows for appropriate allocation of existing
      resources and development of clinical trials testing new treatment strategies for
      patients admitted with heart failure.

PMID- 24122286
TI  - Circulating biomarkers in patients with heart failure and preserved ejection
      fraction.
AB  - Patients with heart failure with preserved ejection fraction (HF-PEF) comprise a
      growing proportion of the overall HF burden. The pathophysiology of HF-PEF is
      complex, and relates to the interplay between cardiac risk factors (notably
      diabetes/insulin resistance, hypertension), systemic inflammation, and comorbid
      medical illness (e.g. chronic kidney disease) that conspire to promote
      endothelial dysfunction, ventricular-vascular stiffening, and diastolic
      dysfunction. Efficient diagnosis and optimal therapy remain challenging in this
      population. Imaging, electrocardiographic, and circulating biomarkers, as well as
      pharmacogenetics, may help to facilitate HF diagnosis, stratify risk, and
      individualize therapy. In this review, we focus on established and emerging
      circulating biomarkers in HF-PE, including circulating biomarkers of myocyte
      stress, myocyte injury, renal function, systemic inflammation, and fibrosis. Such
      markers have contributed to better understanding of the pathophysiologic
      mechanisms relevant to HF-PEF, and may eventually help to facilitate more
      effective and personalized management of this syndrome.

PMID- 24122288
TI  - Satellite cells in human skeletal muscle; from birth to old age.
AB  - Changes in satellite cell content play a key role in regulating skeletal muscle
      growth and atrophy. Yet, there is little information on changes in satellite cell
      content from birth to old age in humans. The present study defines muscle fiber
      type-specific satellite cell content in human skeletal muscle tissue over the
      entire lifespan. Muscle biopsies were collected in 165 subjects, from different
      muscles of children undergoing surgery (<18 years; n = 13) and from the vastus
      lateralis muscle of young adult (18-49 years; n = 50), older (50-69 years; n =
      53), and senescent subjects (70-86 years; n = 49). In a subgroup of 51 aged
      subjects (71 +/- 6 years), additional biopsies were collected after 12 weeks of
      supervised resistance-type exercise training. Immunohistochemistry was applied to
      assess skeletal muscle fiber type-specific composition, size, and satellite cell
      content. From birth to adulthood, muscle fiber size increased tremendously with
      no major changes in muscle fiber satellite cell content, and no differences
      between type I and II muscle fibers. In contrast to type I muscle fibers, type II
      muscle fiber size was substantially smaller with increasing age in adults (r = 
      0.56; P < 0.001). This was accompanied by an age-related reduction in type II
      muscle fiber satellite cell content (r = -0.57; P < 0.001). Twelve weeks of
      resistance-type exercise training significantly increased type II muscle fiber
      size and satellite cell content. We conclude that type II muscle fiber atrophy
      with aging is accompanied by a specific decline in type II muscle fiber satellite
      cell content. Resistance-type exercise training represents an effective strategy
      to increase satellite cell content and reverse type II muscle fiber atrophy.

PMID- 24122289
TI  - Battery of behavioral tests in mice that models age-associated   changes in human
      motor function.
AB  - Motor function in humans can be characterized with tests of locomotion, strength,
      balance, and endurance. The aim of our project was to establish an analogous test
      battery to assess motor function in mice. Male C57BL/6 mice were studied at 3 (n
      = 87), 20 (n = 48) and 26 (n = 43) months of age. Tests assessed locomotion,
      strength, balance/coordination, and endurance capacity in mice. Motor function
      was reduced in the older groups of mice for the locomotion, strength, and
      endurance subdomains (p < 0.001). As indicated with a summary score, motor
      function declined by 7.4 % from 3 to 20 months and by 13.5 % from 20 to 26
      months. Based on comparison with previously published data in humans, the
      magnitude and relative time course of changes were similar in mice and humans in
      each subdomain except balance/coordination. Power calculations confirmed that the
      age-associated differences depicted by several of the individual tests and domain
      summary scores would be sufficient to assess the efficacy of interventions aimed
      at prevention or treatment of motor dysfunction with aging. The current study
      describes a mouse model that characterizes age-associated changes in clinically
      relevant domains of motor function and indicates that the preclinical model can
      be used to test strategies to attenuate age-associated declines in motor
      function.

PMID- 24122291
TI  - The ship as laboratory: making space for field science at sea.
AB  - Expanding upon the model of vessels of exploration as scientific instruments
      first proposed by Richard Sorrenson, this essay examines the changing nature of
      the ship as scientific space on expedition vessels during the late nineteenth
      century. Particular attention is paid to the expedition of H.M.S. Challenger
      (1872-1876) as a turning point in the design of shipboard spaces that established
      a place for scientists at sea and gave scientific legitimacy to the new science
      of oceanography. There was a progressive development in research vessel design
      from "ship as instrument" to "ship as laboratory" and changing spatial practices
      aboard these vessels were paralleled by changes in shipboard culture. I suggest
      that the "ship as laboratory" has now in turn been supplanted by a new model, the
      "ship as invisible technician", as oceanographic research vessels deploy remote
      sensing equipment and gather data that are no longer analyzed on board. 

PMID- 24122290
TI  - Cross-talk between neurons and astrocytes in response to bilirubin: adverse
      secondary impacts.
AB  - Previous studies using monotypic nerve cell cultures have shown that bilirubin
      induced neurological dysfunction (BIND) involves apoptosis and necrosis-like cell
      death, following neuritic atrophy and astrocyte activation,and that
      glycoursodeoxycholic acid (GUDCA) has therapeutic efficacy against BIND. Cross
      talk between neurons and astrocytes may protect or aggravate neurotoxicity by
      unconjugated bilirubin (UCB). In a previous work we have shown that bidirectional
      signaling during astrocyte-neuron recognition attenuates neuronal damage by UCB.
      Here, we investigated whether the establishment of neuron-astrocyte homeostasis
      prior to cell exposure to UCB was instead associated with a lower resistance of
      neurons to UCB toxicity, and if the pro-survival properties of GUDCA were
      replicated in that experimental model. We have introduced a 24 h adaptation
      period for neuron-glia communication prior to the 48 h treatment with UCB. In
      such conditions, UCB induced glial activation, which aggravated neuronal damage,
      comprising increased apoptosis,cell demise and neuritic atrophy, which were
      completely prevented in the presence of GUDCA. Neuronal multidrug resistance
      associated protein 1 expression and tumor necrosis factor-a secretion, although
      unchanged by UCB, increased in the presence of astrocytes. The rise in S100B and
      nitric oxide in the co-cultures medium may have contributed to UCB neurotoxicity.
      Since the levels of these diffusible molecules did not change by GUDCA we may
      assume that they are not directly involved in its beneficial effects. Data
      indicate that astrocytes, in an indirect neuron-astrocyte co-culture model and
      after homeostatic setting regulation of the system, are critically influencing
      neurodegeneration by UCB, and support GUDCA for the prevention of BIND.

PMID- 24122292
TI  - A core microRNA signature associated with inducers of the epithelial-to
      mesenchymal transition.
AB  - Although it is becoming clear that certain miRNAs fulfil a fundamental role in
      the regulation of the epithelial-to-mesenchymal transition (EMT), a comprehensive
      study of the miRNAs associated with this process has yet to be performed. Here,
      we profiled the signature of miRNA expression in an in vitro model of EMT,
      ectopically expressing in MDCK cells one of seven EMT transcription factors
      (SNAI1, SNAI2, ZEB1, ZEB2, TWIST1, TWIST2 or E47) or the EMT inducer LOXL2. In
      this way, we identified a core subset of deregulated miRNAs that were further
      validated in vivo, studying endometrial carcinosarcoma (ECS), a tumour entity
      that represents an extreme example of phenotypic plasticity. Moreover, epigenetic
      silencing through DNA methylation of miRNA genes of the miR-200 family and miR
      205 that are down-regulated during EMT was evident in both the in vitro (MDCK
      transfectants) and in vivo (ECS) models of EMT. The strong correlation between
      expression and DNA methylation suggests a major role for this epigenetic mark in
      the regulation of the miR-141-200c locus.

PMID- 24122293
TI  - Iothalamate versus estimated GFR in a Hispanic-dominant pediatric renal
      transplant population.
AB  - BACKGROUND: Accurate knowledge of glomerular filtration rate (GFR) is essential
      to the practice of nephrology. Routine surveillance of GFR is most commonly
      executed using estimated GFR (eGFR) calculations, most often from serum
      creatinine measurements. However, cystatin C-based equations have demonstrated
      earlier sensitivity to decline in renal function. The literature regarding eGFR
      from cystatin C has few references that include transplant recipients.
      Additionally, for most of the published eGFR equations, patients of Hispanic
      ethnicity have not been enrolled in sufficient numbers. METHODS: The
      applicability of several eGFR equations to the pediatric kidney transplant
      population at our center were compared in the context of determining whether
      Hispanic ethnicity was associated with equation performance. RESULTS: Updated
      Schwartz, CKiD, and Zappitelli eGFR estimation equations demonstrated the highest
      correlations. CONCLUSIONS: The authors recommend further prospective
      investigations to validate and identify factors contributing to these findings.

PMID- 24122295
TI  - Tropism of the in situ growth from biopsies of childhood neuroectodermal tumors
      following transplantation into experimental teratoma.
AB  - Experimental teratoma induced from human pluripotent stem cells with normal
      karyotype can be described as a failed embryonic process and includes besides
      advanced organoid development also large elements of tissue with a prolonged
      occurrence of immature neural components. Such immature components, although
      benign, exhibit strong morphological resemblance with tumors of embryonic
      neuroectodermal origin. Here, we demonstrate that biopsy material from childhood
      tumors of neural embryonic origin transplanted to mature experimental teratoma
      can show an exclusive preference for matching tissue. Tumor specimens from five
      children with; Supratentorial primitive neuroectodermal tumor (sPNET); Pilocytic
      astrocytoma of the brainstem; Classic medulloblastoma; peripheral primitive
      neuroectodermal tumor (pPNET) or neuroblastoma (NB), respectively, were
      transplanted. Analysis of up to 120 sections of each tumor revealed an
      engraftment for three of the transplanted tumors: pPNET, sPNET, and NB, with a
      protruding growth from the latter two that were selected for detailed
      examination. The histology revealed a strict tropism with a non-random
      integration into what morphologically appeared as matched embryonic
      microenvironment recuperating the patient tumor histology. The findings suggest
      specific advantages over xenotransplantation and lead us to propose that
      transplantation to the human embryonic microenvironment in experimental teratoma
      can be a well-needed complement for preclinical in vivo studies of childhood
      neuroectodermal tumors. 

PMID- 24122296
TI  - Mediators of the resistance and aerobic exercise intervention effect on physical
      and general health in men undergoing androgen deprivation therapy for prostate
      cancer.
AB  - BACKGROUND: The objective of the current study was to identify mediators of the
      effects of a combined resistance and aerobic exercise program on perceived
      physical and general health in men undergoing androgen deprivation therapy for
      prostate cancer. METHODS: In total, 57 patients with prostate cancer undergoing
      androgen deprivation therapy were randomly assigned to 12 weeks of resistance and
      aerobic exercise or usual care. The outcome measures of physical and general
      health were assessed by standardized questionnaires. Linear regression analyses
      were conducted on the residual change scores of the variables. The mediating
      effects of fatigue, muscle strength, and functional performance on the
      intervention's effect on physical and general health were examined using the
      product of coefficients method. Bootstrapping was used to calculate the 95%
      confidence intervals (95% CIs). RESULTS: The exercise intervention was found to
      significantly improve physical (beta, 5.03; 95% CI, 1.01-9.04) and general health
      (beta, 12.89; 95% CI, 2.24-23.54). Upper body muscle strength and walking speed
      significantly mediated the intervention effect on physical health (beta, 2.65;
      95% CI, 0.64-5.54), accounting for 53% of the total effect. Walking speed and
      fatigue were found to be mediators in the intervention effect on general health
      (beta, 7.52; 95% CI, 2.16-16.92), accounting for 51% of the total effect.
      CONCLUSIONS: The intervention effects on physical and general health were
      explained by different mediating mechanisms. Walking speed mediated the
      intervention effect on both physical and general health. The intervention effect
      on physical health was further mediated by upper body strength, whereas the
      effect on general health was mediated by fatigue.

PMID- 24122297
TI  - TNFR2 maintains adequate IL-12 production by dendritic cells in inflammatory
      responses by regulating endogenous TNF levels.
AB  - Sepsis-induced immune reactions are reduced in TNF receptor 2 (TNFR2)-deficient
      mice as previously shown. In order to elucidate the underlying mechanisms, the
      functional integrity of myeloid cells of TNFR2-deficient mice was analyzed and
      compared to wild type (WT) mice. The capacity of dendritic cells to produce IL-12
      was strongly impaired in TNF-deficient mice, mirroring impaired production of IL
      12 by WT dendritic cells in sepsis or after LPS or TNF pre-treatment. In
      addition, TNFR2-deficient mice were refractory to LPS pre-treatment and also to
      hyper-sensitization by inactivated Propionibacterium acnes, indicating
      habituation to inflammatory stimuli by the immune response when TNFR2 is lacking.
      Constitutive expression of TNF mRNA in kidney, liver, spleen, colon and lung
      tissue, and the presence of soluble TNFR2 in urine of healthy WT mice supported
      the conclusion that TNF is continuously present in naive mice and controlled by
      soluble TNFR2. In TNFR2-deficient mice endogenous TNF levels cannot be balanced
      and the continuous exposure to enhanced TNF levels impairs dendritic cell
      function. In conclusion, TNF pre-exposure suppresses secondary inflammatory
      reactions of myeloid cells; therefore, continuous control of endogenous TNF by
      soluble TNFR2 seems to be essential for the maintenance of adequate sensitivity
      to inflammatory stimuli. 

PMID- 24122298
TI  - Pulmonary surfactant protein A-induced changes in the molecular conformation of
      bacterial deep-rough LPS lead to reduced activity on human macrophages.
AB  - The lung is constantly exposed to immune stimulation by LPS from inhaled
      microorganisms. A primary mechanism to maintain immune homeostasis is based on
      anti-inflammatory regulation by surfactant protein A (SP-A), a secreted component
      of lung innate immunity. The architecture of LPS aggregates is strongly
      associated with biological activity. We therefore investigated whether SP-A
      affects the physico-chemical properties of LPS. Determination of the three
      dimensional aggregate structure of LPS by small-angle X-ray scattering
      demonstrated that SP-A induced the formation of multi-lamellar aggregate
      structures. Determination of the acyl-chain-fluidity of LPS aggregates by Fourier
      transform infrared (FTIR) spectroscopy showed that the phase transition
      temperature of LPS was reduced in the presence of SP-A. The phosphate groups at
      the diglucosamine backbone of LPS represent important functional groups for the
      bioactivity of LPS. FTIR analysis revealed changes in the vibrational bands nuas
      PO-(2), indicating an interaction of SP-A with the 1-phosphate, but not with the
      4'-phosphate. The physico-chemical changes induced by SP-A were associated with
      up to 90% reduction in LPS-induced TNF-alpha-production by human macrophages. In
      conclusion, our data demonstrate that the SP-A/LPS interaction induces
      conformational changes in LPS aggregates leading to biologically less active
      structures, thereby providing a new molecular mechanism of immune modulation by
      SP-A.

PMID- 24122299
TI  - Un-Earthing Emotions through Art: Facilitating Reflective Practice with Poetry
      and Photographic Imagery.
AB  - In this article, we comment upon and provide an arts-informed example of an
      emotive-focused reflection of a health care practitioner. Specifically, we use
      poetry and photographic imagery as tools to un-earth practitioners' emotions
      within agonizing and traumatic clinical encounters. In order to recognize one's
      own humanness and authentically engage in the art of medicine, we immerse
      ourselves in the first author's poetic and photographic self-reflection. The poem
      and image are intended to inspire interpretation and meaning based on the
      reader's own professional and/or personal context. The last line of the poem is
      "I take off the gloves. My hands are marked."

PMID- 24122300
TI  - High radiation and desiccation tolerance of nitrogen-fixing cultures of the
      cyanobacterium Anabaena sp. strain PCC 7120 emanates from genome/proteome repair
      capabilities.
AB  - The filamentous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC 7120 was
      found to tolerate very high doses of 60Co-gamma radiation or prolonged
      desiccation. Post-stress, cells remained intact and revived all the vital
      functions. A remarkable capacity to repair highly disintegrated genome and
      recycle the damaged proteome appeared to underlie such high radioresistance and
      desiccation tolerance. The close similarity observed between the cellular
      response to irradiation or desiccation stress lends strong support to the notion
      that tolerance to these stresses may involve similar mechanisms.

PMID- 24122301
TI  - Impact of S100A8/A9 expression on prostate cancer progression in vitro and in
      vivo.
AB  - The proinflammatory S100A8/A9 proteins, which are expressed in myeloid cells
      under physiological conditions, are strongly expressed in human prostate cancer
      epithelial cells. Their role in the tumor cells and in tumor progression is
      largely unclear. We established a prostate cancer epithelial cell line (PC-3 TO
      A8/A9) expressing S100A8 and S100A9 simultaneously under doxycycline control, to
      study the role of S100A8/A9 on tumor growth and infiltration of immune cells in
      subcutaneous xenografts in male NMRI nu/nu mice. Colonization of distant organs
      was studied after intracardial injection of the tumor cells in male NOD/SCID
      mice. PC-3 TO-A8/A9 cells grown in vitro and subcutaneous xenografts in mice not
      treated with doxycycline expressed high levels of S100A8/A9 mRNA and protein,
      whereas doxycycline treatment suppressed S100A8/A9 expression. S100A8/A9
      expression did not significantly alter growth rate and invasion of the
      subcutaneous tumors into surrounding tissues. However, S100A8/A9 expression
      caused increased infiltration of immune cells, especially neutrophils. In
      intracardially injected mice sporadic tumor settlement was observed in muscle and
      lymph nodes. Colonies of tumor cells and micro-metastases were observed in the
      lung of 64.3% (9 out of 14) of mice not treated with doxycycline and in 33.3% (5
      out of 15) of mice treated with doxycycline. Our data demonstrate for the first
      time that S100A8/A9 expression in epithelial cancer cells causes enhanced
      infiltration of immune cells, especially neutrophils, and stimulates settlement
      of the cancer cells in the lung.

PMID- 24122302
TI  - Molecular factors associated with recurrence and survival following hepatectomy
      in patients with intrahepatic cholangiocarcinoma: a guide to adjuvant clinical
      trials.
AB  - BACKGROUND: This study sought to determine clinical and molecular factors related
      to recurrence and survival in patients with ICC following hepatectomy. METHODS:
      Database review identified 34 patients. Molecular markers (Ki67, p53, beta
      catenin) and standard pathological evaluations were performed. RESULTS: The most
      common resections were right (n = 11), extended right (n = 8), and left
      hepatectomy (n = 7). The 30- and 90 -day mortality rates were 5.9% and 11.8%. The
      median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and
      ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months.
      The median disease-free interval was 6 months. The median overall survival was
      37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and
      differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03;
      OR = 0.38; 95% CI: 0.17-0.89) remained significant. Univariate predictors of
      survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02),
      satellite nodules (P = 0.006), beta-catenin expression (P = 0.008), and
      recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR
      = 3.15, 95% CI: 0.96-10.4) and beta-catenin (P = 0.04, OR = 3.23; 95% CI: 1.1
      9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18
      0.98) was an additional predictor. CONCLUSION: Future clinical trials could
      include certain molecular and pathologic factors to assist in determining the
      necessity and type of adjuvant therapy.

PMID- 24122303
TI  - Cost-utility of ranolazine for the symptomatic treatment of patients with chronic
      angina pectoris in Spain.
AB  - BACKGROUND: Ranolazine is an antianginal agent that was approved in the EU in
      2008 as an add-on therapy for symptomatic chronic angina pectoris treatment in
      patients who are inadequately controlled by, or are intolerant to, first-line
      antianginal therapies. These patients' quality of life is significantly affected
      by more frequent angina events, which increase the risk of revascularization.
      OBJECTIVE: To assess the cost-utility of ranolazine versus placebo as an add-on
      therapy for the symptomatic treatment of patients with chronic angina pectoris in
      Spain. METHODS: A decision tree model with 1-year time horizon was designed.
      Transition probabilities and utility values for different angina frequencies were
      obtained from the literature. Costs were obtained from Spanish official DRGs for
      patients with chronic angina pectoris. We calculated the incremental cost-utility
      ratio of using ranolazine compared with a placebo. Sensitivity analyses, by means
      of Monte Carlo simulations, were performed. Acceptability curves and expected
      value of perfect information were calculated. RESULTS: The incremental cost
      utility ratio was ?8,455 per quality-adjusted life-year (QALY) per patient in
      Spain. Sensitivity analyses showed that if the decision makers' willingness to
      pay is ?15,000 per QALY, the treatment with ranolazine will be cost effective at
      a 95 % level of confidence. The incremental cost-utility ratio is particularly
      sensitive to changes in utility values of those non-hospitalized patients with
      mild or moderate angina frequency. CONCLUSIONS: Ranolazine is a highly efficient
      add-on therapy for the symptomatic treatment of chronic angina pectoris in
      patients who are inadequately controlled by, or intolerant to, first-line
      antianginal therapies in Spain.

PMID- 24122304
TI  - Picoelectrospray ionization mass spectrometry using narrow-bore chemically etched
      emitters.
AB  - Electrospray ionization mass spectrometry (ESI-MS) at flow rates below ~10 nL/min
      has been only sporadically explored because of difficulty in reproducibly
      fabricating emitters that can operate at lower flow rates. Here we demonstrate
      narrow orifice chemically etched emitters for stable electrospray at flow rates
      as low as 400 pL/min. Depending on the analyte concentration, we observe two
      types of MS signal response as a function of flow rate. At low concentrations, an
      optimum flow rate is observed slightly above 1 nL/min, whereas the signal
      decreases monotonically with decreasing flow rates at higher concentrations. For
      example, consumption of 500 zmol of sample yielded signal-to-noise ratios ~10 for
      some peptides. In spite of lower MS signal, the ion utilization efficiency
      increases exponentially with decreasing flow rate in all cases. Significant
      variations in ionization efficiency were observed within this flow rate range for
      an equimolar mixture of peptide, indicating that ionization efficiency is an
      analyte-dependent characteristic for the present experimental conditions. Mass
      limited samples benefit strongly from the use of low flow rates and avoiding
      unnecessary sample dilution. These findings have important implications for the
      analysis of trace biological samples.

PMID- 24122305
TI  - Measuring positive cooperativity using the direct ESI-MS assay. Cholera toxin B
      subunit homopentamer binding to GM1 pentasaccharide.
AB  - Direct electrospray ionization mass spectrometry (ESI-MS) assay was used to
      investigate the stepwise binding of the GM1 pentasaccharide beta-D-Galp-(1->3)
      beta-D-GalpNAc-(1->4)[alpha-D-Neu5Ac-(2->3)]-beta-D-Galp-(1->4)-beta-D-Glcp
      (GM1os) to the cholera toxin B subunit homopentamer (CTB5) and to establish
      conclusively whether GM1os binding is cooperative. Apparent association constants
      were measured for the stepwise addition of one to five GM1os to CTB5 at pH 6.9
      and 22  degrees C. The intrinsic association constant, which was established from
      the apparent association constant for the addition of a single GM1os to CTB5, was
      found to be (3.2 +/- 0.2) * 106 M(-1). This is in reasonable agreement with the
      reported value of (6.4 +/- 0.3) * 106 M(-1), which was measured at pH 7.4 and 25 
      degrees C using isothermal titration calorimetry (ITC). Analysis of the apparent
      association constants provides direct and unambiguous evidence that GM1os binding
      exhibits small positive cooperativity. Binding was found to be sensitive to the
      number of ligand-bound nearest neighbor subunits, with the affinities enhanced by
      a factor of 1.7 and 2.9 when binding occurs next to one or two ligand-bound
      subunits, respectively. These findings, which provide quantitative support for
      the binding model proposed by Homans and coworkers [14], highlight the unique
      strengths of the direct ESI-MS assay for measuring cooperative ligand binding.

PMID- 24122308
TI  - [Current trends in psychotherapy research: indications of a paradigm change?].

PMID- 24122309
TI  - [The outpatient provision of care for psychiatric patients in a rural area].
AB  - An analysis of reimbursement claims in Mecklenburg West-Pomerania from the year
      2007 showed that of all reimbursement claims made for outpatient treatment of
      patients with mental disorders, the majority has been claimed by general
      practitioners. Using the reimbursement claims from the last 3 months from 2010,
      again, most treatment claims were made by general practitioners. The patients
      were treated by general practitioners in 50.5%. neurologists/psychiatrists 16%,
      internal practitioners 10.6%, gynaecologists 5.3% and by psychotherapists in
      2.3%. The actual analyses of reimbursement claims show again that the majority of
      patients with psychiatric disorders is not treated by the respective professional
      group.

PMID- 24122307
TI  - Prevalence of feeding disorders in children with cleft palate only: a
      retrospective study.
AB  - OBJECTIVES: The purpose of this study in children with cleft palate only (CPO) is
      to (1) explore the prevalence of feeding problems on a retrospective basis, (2)
      investigate rates of nasogastric (NG) feeding, (3) examine the prevalence of
      associated disorders and/or syndromes (AssD/S), (4) investigate if there are
      certain risk factors associated with feeding difficulties, NG feeding, and
      failure of breastfeeding, and (5) investigate the effect of palatoplasty on
      feeding difficulties. MATERIALS AND METHODS: In total, 90 questionnaires were
      included in this study. The medical records were reviewed. RESULTS: Feeding
      difficulties were reported in 67% (n = 60) of all cases. NG feeding was given in
      32% (n = 28) of all children. Forty-nine children (54%) have associated
      malformations. There is no significant relation for gender, gestational age, and
      birth weight as risk factors for feeding difficulties, NG feeding, and failure of
      breastfeeding. The severity of the cleft is significantly related to the
      prevalence of AssD/S. After palatoplasty, feeding difficulties improved in 79% of
      the CPO children. CONCLUSIONS AND CLINICAL RELEVANCE: First, our results clearly
      indicate that children with CPO are at high risk of developing feeding
      difficulties (67%); NG feeding is often necessary (32%). Second, our results also
      indicate that the more severe the cleft, the more likely the chance for AssD/S.
      Third, the severity of the cleft is significantly related to the prevalence of
      AssD/S. Fourth, there is no significant relation for gender, gestational age, and
      birth weight as risk factors for feeding difficulties, NG feeding, and failure of
      breastfeeding. Fifth, improvement of feeding difficulties after surgery supports
      the importance of the soft palate closure in relation to sucking patterns and
      feeding skills.

PMID- 24122306
TI  - An update on medical therapy for pulmonary arterial hypertension.
AB  - Over the past 20 years, great progress has been made in the treatment of
      pulmonary arterial hypertension (PAH). Available therapies target one of three
      principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin
      (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or
      in different combinations, can improve exercise capacity, clinical symptoms,
      hemodynamics and even survival in PAH. Unfortunately, the disease remains
      incurable and the prognosis of the disease is still poor. However, existing and
      novel potent antiproliferative therapies are being explored, and new agents
      targeting different and/or additional pathways are likely to become available to
      clinicians in the near future. Promising candidates include tyrosine kinase
      antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat);
      an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin
      receptor antagonist (macitentan). Phase II or III trials have either been
      completed or are underway to evaluate the safety and efficacy of these various
      therapies.

PMID- 24122310
TI  - [Writing therapy after traumatic events: therapeutic approaches and mechanisms of
      change].
AB  - The (written) disclosure of information, thoughts and emotions of individually
      significant tops is associated with positive effects on well-being and the
      psychological health. The applicability of expressive writing as a
      psychotherapeutic intervention for stress reactions after stressful/traumatic
      life events were also intensely discussed in the clinical context. However,
      structural and content-related variation of the initial writing paradigm resulted
      in significantly different effects on general psychological health and
      posttraumatic stress symptoms.This overview provides current findings to
      application and efficacy of expressive writing respectively writing therapy for
      posttraumatic stress disorder. Mechanisms of expressive writing (inhibition,
      habituation, construction of a coherent narrative, emotion regulation, social
      integration) are analyzed with regard to their relevance concerning PTSD.
      Finally, potentials for application in the clinical practice are discussed. 

PMID- 24122311
TI  - [Addressing publication bias].

PMID- 24122312
TI  - [Psychological counseling and psychotherapy in unwanted childlessness].

PMID- 24122313
TI  - [Reports from the German College of Psychosomatic Medicine].

PMID- 24122314
TI  - Two novel susceptibility SNPs for ischemic stroke using exome sequencing in
      Chinese Han population.
AB  - Genome-wide association studies (GWAS) of ischemic stroke (IS) have been
      performed on several cohorts of Caucasian or African population and Japanese,
      resulting in somewhat inconsistent conclusion. We aimed to identify
      susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome
      sequencing was used to screen susceptibility loci among 100 cases and 100 matched
      controls. Significant SNPs from the first stage were verified in up to 3,554
      participants from three hospital-based case-control studies. In the initial exome
      sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p <
      1 * 10(-8)) and rs17118 in XYLB gene located on chromosome 3p21 (p < 1 * 10(-6))
      were found to be significantly associated with IS. In the following validation
      stage, significantly increased odds ratios were observed in individuals with
      rs10489177 GG (OR = 2.02, 95 % CI = 1.35-3.03) or rs17118 AA genotype (OR = 1.50,
      95 % CI = 1.17-1.91). The rs10489177 GG genotype was associated with
      significantly increased risk for IS in individuals without hypertension (OR =
      2.78, 95 % CI = 1.59-4.86) and in individuals without diabetes (OR = 1.93, 95 %
      CI = 1.27-2.94). In contrast, the rs17118 AA genotype may significantly increase
      the risk for IS, particularly for individuals with hypertension (OR = 1.73, 95 %
      CI = 1.08-2.78) and for individuals without diabetes (OR = 1.52, 95 % CI = 1.17
      1.98) or non-smoker (OR = 1.59, 95 % CI = 1.16-2.19). Collectively, our study
      identified two novel loci (rs17118 and rs10489177) which were associated with an
      increased risk for IS in Chinese Han populations. Further studies are needed to
      confirm these associations in other populations and elucidate the biological
      mechanisms underlying the observed associations.

PMID- 24122315
TI  - Combinatorial engineering of mevalonate pathway for improved amorpha-4,11-diene
      production in budding yeast.
AB  - Combinatorial genome integration of mevalonate pathway genes was performed with
      the aim of optimizing the metabolic flux for improved production of terpenoids in
      budding yeast. In the present study, we developed a novel delta-integration
      platform to achieve multiple genome integrations through modulating the
      concentration of antibiotics. By exploiting carotenoid biosynthesis as screening
      module, we successfully created a library of yeast colonies appeared with various
      intensities of orange color. As proof-of-concept that carotenoid overproducers
      could serve to boost the titer of other terpenoids, we further tested engineered
      strains for the production of amorpha-4,11-diene, an important precursor for
      antimalarial drug. However, we experienced some limitations of the carotenoid
      based screening approach as it was only effective in detecting a small range of
      pathway activity improvement and further increasing mevalonate pathway activity
      led to a decreased orange color. By far, we were only able to obtain one mutant
      strain yielded more than 13-fold amorpha-4,11-diene over parental strains, which
      was approximately 64 mg/L of caryophyllene equivalents. Further qPCR studies
      confirmed that erg10, erg13, thmg1 and erg12 involved in mevalonate pathway were
      overexpressed in this mutant strain. We envision the current delta-integration
      platform would form the basis of a generalized technique for multiple gene
      integrations in yeast-a method that would be of significant interest to the
      metabolic engineering community.

PMID- 24122316
TI  - Metastasis of renal cell carcinoma to the duodenal papilla.

PMID- 24122317
TI  - Prognostic factors in acute-on-chronic liver failure: a prospective study from
      western India.
AB  - The profile of acute-on-chronic liver failure (ACLF) has not been reported from
      western India. This study was undertaken to analyze the etiology and clinical
      profile of patients with ACLF and correlate these with outcome. Fifty-four
      consecutive cases of ACLF were investigated for underlying chronic liver disease
      (CLD) and acute insult and followed up for 6 months. Mortality, Child-Pugh score,
      and model for end-stage liver disease (MELD) score were recorded. The most common
      etiologies of CLD were hepatitis B (29.6 %) and cryptogenic (27.7 %). Prognosis
      was worse in patients with hepatitis B or alcohol as cause of CLD (mortality 79
      %). Acute viral hepatitis A or E was the commonest cause of acute insult (33.3 %)
      and with statistically better outcome (60 % survival) as compared to sepsis,
      gastrointestinal bleed, or flare of HBV (survival 5 %, p < 0.05). On univariate
      analysis age, past history of decompensation, leukocytosis, serum bilirubin and
      creatinine, international normalized ratio, presence of spontaneous bacterial
      peritonitis, Child-Pugh score and hepatorenal syndrome were significant
      predictors of mortality. Multivariate analysis revealed a MELD score of >27 and
      presence of encephalopathy as independent predictors of mortality. Patients with
      ACLF had high mortality especially when they had underlying chronic hepatitis B
      or alcoholic liver disease. Presence of encephalopathy and MELD score were
      independent baseline predictors of mortality. Child-Pugh score was helpful for
      prognostication.

PMID- 24122318
TI  - Flavor preferences conditioned by intragastric monosodium glutamate in mice.
AB  - The consumption of monosodium glutamate (MSG) solutions has been shown to
      reinforce preferences for MSG and for MSG-paired flavors in mice. These effects
      appear to have a strong postoral component, such that MSG detected in the gut is
      associated with concurrently consumed flavors. Two experiments investigated
      postoral MSG reward by infusing 400mM MSG intragastrically (IG) to C57BL/6 mice
      as they consumed a conditioned stimulus (CS+) flavor. An alternate CS- flavor was
      paired with IG water. In Experiment 1, the grape and cherry CS flavors were
      unsweetened, and intakes and preferences for the CS+ flavor were modest.
      Experiment 2 attempted to generate stronger preferences by adding 0.05% saccharin
      to the CS flavors. Sweet taste did enhance intakes during training and testing
      but did not significantly increase percent CS+ intake or persistence of the
      preference. However, only conditioning with the sweet CS+ resulted in the mice
      expressing a preference for oral MSG in an initial choice test with water. These
      findings extend recent studies demonstrating postoral MSG conditioning in rats. 

PMID- 24122319
TI  - Investigation of nasal CO2 receptor transduction mechanisms in wild-type and GC-D
      knockout mice.
AB  - The main olfactory system of mice contains a small subset of olfactory sensory
      neurons (OSNs) that are stimulated by CO2. The objective of this study was to
      record olfactory receptor responses to a range of CO2 concentrations to further
      elucidate steps in the proposed CO2 transduction pathway in mice. Electro
      olfactograms (EOGs) were recorded before and after inhibiting specific steps in
      the CO2 transduction pathway with topically applied inhibitors. Inhibition of
      extracellular carbonic anhydrase (CA) did not significantly affect EOG responses
      to CO2 but did decrease EOG responses to several control odorants. Inhibition of
      intracellular CA or cyclic nucleotide-gated channels attenuated EOG responses to
      CO2, confirming the role of these components in CO2 sensing in mice. We also show
      that, like canonical OSNs, CO2-sensitive OSNs depend on Ca2+-activated Cl-
      channels for depolarization of receptor neurons. Lastly, we found that guanylyl
      cyclase-D knockout mice were still able to respond to CO2, indicating that other
      pathways may exist for the detection of low concentrations of nasal CO2. We
      discuss these findings as they relate to previous studies on CO2-sensitive OSNs
      in mice and other animals.

PMID- 24122320
TI  - Olfactory cocainization is not an effective long-term treatment for phantosmia.
AB  - Phantosmia, the perception of an odor when there are no odorants in the
      environment, can be a very debilitating symptom. In the 1960s, Zilstorff reported
      olfactory distortions could be treated by the topical application of a cocaine
      solution to the olfactory epithelium. In evaluating this treatment, we observed
      no long-term benefit using cocaine on 6 patients with phantosmia. Based on our
      observations, the patient's olfactory ability was not a determining factor in the
      initiation or quality of their phantosmia. Following topical cocainization, we
      observed a remarkable delay of hours to days in the return of olfactory ability,
      and when cocaine was applied to only 1 nostril, there was a decreased olfactory
      ability on the noncocainized side. These results may suggest the possibility that
      phantosmia is related to a central processing problem. 

PMID- 24122321
TI  - Flavor preferences conditioned by oral monosodium glutamate in mice.
AB  - The prototypic umami substance monosodium glutamate (MSG) reinforces preferences
      for its own flavor, as well as preferences for flavors associated with it, by
      conditioning processes. Mice of 3 inbred strains (C57BL/6J (B6), 129P3/J, and
      FVB/NJ) and 2 taste-knockout (KO) groups derived from the B6 lineage were
      initially indifferent to 200mM MSG, but this evaluation was altered by forced
      exposure to MSG. B6 and KO mice acquired an MSG preference, 129 mice remained
      indifferent, and FVB mice avoided MSG. The shifts in preference imply a postoral
      basis for MSG effects, suggesting that it could produce preferences for
      associated flavors. New mice were trained with a conditioned stimulus (CS+)
      flavor mixed in 200mM MSG and a CS- flavor in water. Similar to the parent B6
      strain, mice missing the T1r3 element of an umami receptor or the downstream
      signaling component Trpm5 learned to prefer the CS+ flavor and subsequently
      showed similar preferences for MSG in an ascending concentration series.
      Consistent with their responses to forced exposure, the 129 strain did not
      acquire a significant CS+ preference, and the FVB strain avoided the CS+ flavor.
      The 129 and FVB strains showed little attraction in the ascending MSG
      concentration series. Together, these data indicate that the postoral effects of
      MSG can modulate responses to its own and MSG-paired flavors. The basis for
      strain differences in the responses to MSG is not certain, but the taste
      signaling elements T1r3 and Trpm5, which are also present in the gut, are not
      required for mediation of this flavor learning. 

PMID- 24122322
TI  - Bottom-up approach to construct microfabricated multi-layer scaffolds for bone
      tissue engineering.
AB  - The use of bottom-up approaches in tissue engineering applications is
      advantageous since they enable the combination of various layers that could be
      made from different materials and/or incorporate different biochemical cues.
      Regarding the complex structure and the vascular system of the bone tissue, the
      aim of this study was to develop an innovative bottom-up approach that allows the
      construction of 3D biodegradable scaffolds from 2D microfabricated membranes with
      precise shape, pore size and porosity. For that purpose, poly (caprolactone)
      (PCL) and starch - poly (caprolactone) (SPCL (30 % starch)) blended sheets were
      used as substrates to produce the microfabricated membranes using micro
      hotembossing. The use of this micro fabrication process allowed accurately
      imprinting micropillars and microholes in reproducible way. The assembling of the
      microfabricated membranes was performed using an easy, highly reproducible and
      inexpensive approach based on its successive stacking. Additionaly, the
      suitability of the microfabricated membranes to support the attachment and the
      cytoskeletal organization of human bone marrow stem cells (hBMSCs), macrovascular
      endothelial cells and osteoblasts derived from hBMSCs was demonstrated.
      Furthermore, hBMSCs proliferated and maintained the expression of the stromal
      progenitor marker STRO-1 when cultured on both PCL and SPCL microfabricated
      membranes. The proposed methodology constitutes a promising alternative to the
      traditional processing methods used to prepare tissue engineering scaffolds.

PMID- 24122323
TI  - Assessing the fidelity of the Kin KeeperSM prevention intervention in African
      American, Latina and Arab women.
AB  - BACKGROUND: We evaluated a randomized controlled treatment, utilizing Community
      Health Workers (CHW) to deliver breast and cervical cancer education intervention
      to African American, Latina, and Arab women in Detroit and Dearborn, Michigan.
      The main objectives of the study are to: (1) examine fidelity and consistency of
      treatment delivery and (2) assess qualitative elements of the intervention.
      METHODS: We surveyed 305 women who received the intervention and 16 CHWs Survey
      included questions regarding the treatment integrity, treatment received, and
      training provided. Surveys included both quantitative and questions. RESULTS: The
      intervention group (n = 305) was made up of 48% Black, 11% Latina, and 41% Arab
      women. Almost all (>= 90%) women agreed that they received the treatment in the
      way that it was intended. Sixteen CHWs responded affirmatively as well.
      CONCLUSIONS: Both participants and CHWs indicated that the program was mutually
      rewarding, indicating that there was "cross fertilization and cross benefit" of
      working with each other. These benefits served to endorse and confirm that CHWs
      are a very important mechanism in increasing health literacy in the community and
      referring underserved individuals to health providers. Second, with strong
      treatment fidelity the Kin Keeper(SM) program and has the potential to be
      replicated for a number of diseases in a variety of venues especially for those
      facing health disparities.

PMID- 24122325
TI  - Vasculorama.

PMID- 24122324
TI  - Factors associated with the completion of falls prevention program.
AB  - Falls and fear of falling can affect independence and quality of life of older
      adults. Falls prevention programs may help avoiding these issues if completed.
      Understanding factors that are associated with completion of falls prevention
      programs is important. To reduce fear of falling and increase activity levels, a
      Matter of Balance (MOB) and un Asunto de Equilibrio (ADE) workshops were offered
      to 3420 older adults in South Florida between 1 October 2008 and 31 December
      2011. Workshops were conducted in English or Spanish over eight, 2-hour sessions.
      Participants completed a demographic and a pre-post questionnaire. Factors
      associated with program completion were identified using logistic regression. For
      MOB, females were more likely to complete the program (OR = 2.076, P = 0.02). For
      ADE, females, moderate and extreme interference by falls in social activities
      were found to affect completion (OR = 2.116, P = 0.001; OR = 2.269, P = 0.003 and
      OR = 4.133, P = 0.008, respectively). Different factors predicted completion of
      both programs. Awareness of these factors can help lower the attrition rates,
      increase benefits and cost effectiveness of program. Future research needs to
      explore why certain groups had a higher likelihood of completing either program. 

PMID- 24122326
TI  - Placement of tunnelled hemodialysis catheters across stenotic and occluded
      central veins.
AB  - PURPOSE. The purpose of this study was to evaluate the efficacy of placement of
      tunneled hemodialysis catheters in patients with occluded or stenotic central
      veins. MATERIALS AND METHODS. Data were prospectively collected for 26 patients
      (11 male, 15 female, mean age 52 years) referred for placement of tunneled
      hemodialysis catheters with central venous stenoses or occlusions. The central
      venous occlusions or stenoses were recanalized using traditional interventional
      catheter and guidewire techniques.<br />RESULTS. Thirty central venous access
      procedures were performed of which 28 (93%) procedures resulted in successful
      tunneled catheter insertion. Twenty-one internal jugular venous (13 right, 8
      left) and 7 subclavian venous (3 right, 4 left) catheters were placed. Eighteen
      stenotic and 10 occluded venous segments were crossed including the
      brachiocephalic vein (n = 22), subclavian vein (n = 2), and the superior vena
      cava (4). One patient required insertion of a metallic stent to facilitate
      passage of the hemodialysis catheter across an occluded brachiocephalic vein. No
      procedure-related complications occurred. No episodes of upper extremity swelling
      or superior vena cava syndrome occurred following catheter insertion.<br
      />CONCLUSIONS. Insertion of tunneled hemodialysis catheter across occluded or
      stenotic central veins is technically feasible and safe. The use of occluded or
      stenotic central veins for catheter access preserves patent central veins for
      future shunt access. 

PMID- 24122327
TI  - Association of various point mutations as risk factors for synthetic graft
      thrombosis in African American hemodialysis patients.
AB  - Single-nucleotide polymorphisms in the genes that code for coagulation factor V
      (factor V (Leiden)) and II (prothrombin G20210A), as well as the
      methyltetrahydrofolate reductase (MTHFR) have been implicated in the majority of
      cases of hereditary thrombophilia. In our hemodialysis patient population,
      comprised mainly of African Americans, we have seen a high incidence of early
      vascular access thrombosis without any identifiable predisposing factors. In some
      instances, there is recurrent access thrombosis that may be related to an
      inherited condition. In this study we evaluated the presence of these gene
      mutations and their association with increased risk of recurrent vascular access
      thrombosis in our hemodialysis patient population. Our results show that factor V
      Leiden and factor II prothrombin point mutations did not appear to increase the
      risk of vascular access thrombosis in African Americans with end-stage renal
      disease on hemodialysis. Patients heterozygous for the MTHFR gene, also did not
      show a significant increased risk for synthetic graft thrombosis. 

PMID- 24122328
TI  - No association between hyperhomocysteinemia and vascular access thrombosis in
      chronic hemodialysis.
AB  - PURPOSE. Hyperhomocysteinemia, recognized as a risk factor for cardiovascular
      diseases, has also been related with controversy to vascular access thrombosis in
      hemodialysis. Our objective was to determine if such an association could be
      found in our hemodialysis population. METHODS. The survey was conducted in a
      cohort of 165 chronic hemodialysis patients. Their vascular access history was
      considered from hemodialysis initiation until November 1999, including the number
      of vascular accesses created (either native or synthetic fistulae), focussing on
      vascular access thrombotic events, and excluding primary vascular access
      dysfunction. Diabetes, hemoglobin, erythropoietin dose, anticoagulation, and
      methyltetrahydrofolate reductase (MTHFR) status were considered. Serum total
      homocysteine (tHcy) measures were sampled for all patients in June 1998 and
      repeated yearly. Patients had not been supplemented routinely with hydrosoluble
      vitamins until June 1998, after which all received DiaVite (R&D Laboratories, CA,
      USA) daily. RESULTS. Median survival of native fistulae was significantly longer
      (81 months, 95%CI 35-127) than for synthetic fistulae (31 months, 95%CI 27-51).
      Median vascular access survival was reduced for diabetics vs non diabetics (28 vs
      57 months) (p<0.05), whereas sex, age and smoking had no impact. No correlation
      was found between tHcy concentration and the number of vascular access thrombotic
      events; homozygotes for MTHFR had higher tHcy but no more vascular access
      thrombotic events. The 38 patients with a mean vascular access survival of less
      than 12 months (63 months) were compared to the 127 patients with a mean vascular
      access survival of >= 12 months (3925 months) (p<0.05): no difference in their
      respective tHcy concentrations before and after DiaVite introduction was found
      (3113 and 208 vs 3417 and 226 mol/L), but the first group presented more numerous
      synthetic fistulae (p<0.0001), lower hemoglobin levels, and higher erythropoietin
      doses. CONCLUSIONS. No significant association between hyperhomocysteinemia and
      vascular access thrombosis could be found in our population. DiaVite introduction
      allowed a significant reduction in tHcy, but had no impact on vascular access
      survival, except for a slight but not significant reduction in the prevalence of
      vascular access thrombotic events during the year on DiaVite. Potential benefits
      of approaches to reduce tHcy for vascular access time-life prolongation remain to
      be demonstrated. 

PMID- 24122329
TI  - Superficialization of basilic vein: last chance for a native arteriovenous
      fistula in hemodialysis patients.
AB  - BACKGROUND: Although the best type of vascular access for chronic hemodialysis
      patients is a native arteriovenous fistula, in an increasing number of patients
      all the superficial veins have been used and only the placement of vascular
      grafts or permanent catheters is left. Superficialization of the basilic vein is
      a possible alternative.<br /> MATERIALS AND METHODS: In 49 chronic hemodialysis
      patients who had no possibilities to have a native arteriovenous fistula created,
      we performed a basilic vein- brachial artery fistula in the arm. During the same
      operation the basilic vein was then superficialized for easier access for
      hemodialysis. RESULTS: Mean follow-up was 22.3615.56 months. Forty-eight patients
      are still undergoing hemodialysis with their superficialized basilic vein native
      A-V fistula without any complications. Only one fistula was thrombosed just after
      the procedure because of poor vessel quality. CONCLUSIONS: For hemodialysis
      patients who have no suitable superficial veins at the wrist or elbow, performing
      a basilic vein - brachial artery fistula and superficializing the vein to the
      subcutaneous tissue is an acceptable choice before deciding to use more
      complicated procedures like vascular grafts.

PMID- 24122330
TI  - Knowledge of the anomalies of the big central veins reduces the morbidity during
      the cannulation for hemodialysis: Description of a case of persistent left
      superior vena cava and revision of literature.
AB  - The persistence of a left superior vena cava is the result of a lack of an
      embryological involution of the left anterior cardinal vein. This anomaly is very
      rare: about 0.3% of the general population. Its incidence increases remarkably
      from 3-10% in those patients affected with congenital heart disease. Described
      herein is a case of persistent left superior vena cava, discovered by chance,
      following the placement of a central venous catheter for hemodialysis. A chest X
      ray in projection back-forward showed the central venous catheter along the left
      sternal margin simulating a placement in the aorta artery. This clinical picture,
      as described in the literature, is often accompanied by other anatomical
      anomalies, in our case, by the congenital agenesis of a solitary pelvic kidney.
      In agreement with the literature and in contrast with what has been reported
      recently, we sustain that a central venous catheter placed, for any reason, in
      the persistent left superior vena cava must be removed immediately because it can
      induce hyperkinetic arrhythmia and cardiac arrest as in our case. Our case report
      should be a warning that lack of awareness of the anomalies of the big central
      veins can cause a rise in morbidity. 

PMID- 24122331
TI  - Hepatic abscess and umbilical venous catheter: one cannot be cavalier about
      proper position.
AB  - PURPOSE The umbilical venous catheter (UVC) is routinely used in neonatal
      intensive care. Incorrect placement may expose the patient to some dangerous
      complications (i.e. thrombosis, abscesses, etc). We report a case of an hepatic
      abscess due to incorrect positioning of this device. We describe how the abscess
      was treated and we emphasize that one cannot be cavalier about proper positioning
      of the UVC. 

PMID- 24122332
TI  - Ototoxicity from the aminoglycoside-heparin/ citrate locks applied for the
      prevention of hemodialysis catheter-related infections.

PMID- 24122334
TI  - The network of P-glycoprotein and microRNAs interactions.
AB  - Overexpression of P-glycoprotein (P-gp) contributes to the multidrug resistance
      (MDR) phenotype found in many cancer cells. P-gp has been identified as a
      promising molecular target, although attempts to find successful therapies to
      counteract its function as a drug efflux pump have largely failed to date. Apart
      from its role in drug efflux, P-gp may have other cellular functions such as
      being involved in apoptosis, and is found in various locations in the cell. Its
      expression is highly regulated, namely by microRNAs (miRNAs or miRs). In
      addition, P-gp may regulate the expression of miRs in the cell. Furthermore, both
      P-gp and miRs may be found in microvesicles or exosomes and may be transported to
      neighboring, drug-sensitive cells. Here, we review this current issue together
      with recent evidence of this network of interactions between P-gp and miRs. 

PMID- 24122335
TI  - Pathology in drug discovery and development.
AB  - The rapid pace of drug discovery and drug development in oncology, immunology and
      ophthalmology brings new challenges; the efficient and effective development of
      new targeted drugs will require more detailed molecular classifications of
      histologically homogeneous diseases that show heterogeneous clinical outcomes. To
      this end, single companion diagnostics for specific drugs will be replaced by
      multiplex diagnostics for entire therapeutic areas, preserving tissue and
      enabling rapid molecular taxonomy. The field will move away from the development
      of new molecular entities as single agents, to which resistance is common.
      Instead, a detailed understanding of the pathological mechanisms of resistance,
      in patients and in preclinical models, will be key to the validation of
      scientifically rational and clinically effective drug combinations. To remain at
      the heart of disease diagnosis and appropriate management, pathologists must
      evolve into translational biologists and biomarker scientists. Herein, we provide
      examples of where this metamorphosis has already taken place, in lung cancer and
      melanoma, where the transformation has yet to begin, in the use of
      immunotherapies for ophthalmology and oncology, and where there is fertile soil
      for a revolution in treatment, in efforts to classify glioblastoma and
      personalize treatment. The challenges of disease heterogeneity, the regulatory
      environment and adequate tissue are ever present, but these too are being
      overcome in dedicated academic centres. In summary, the tools necessary to
      overcome the 'whens' and 'ifs' of the molecular revolution are in the hands of
      pathologists today; it is a matter of standardization, training and leadership to
      bring these into routine practice and translate science into patient benefit.
      This Annual Review Issue of the Journal of Pathology highlights the central role
      for pathology in modern drug discovery and development.

PMID- 24122336
TI  - Oxidative stress management in the filamentous, heterocystous, diazotrophic
      cyanobacterium, Anabaena PCC7120.
AB  - Reactive oxygen species (ROS) are inevitably generated as by-products of
      respiratory/photosynthetic electron transport in oxygenic photoautotrophs. Unless
      effectively scavenged, these ROS can damage all cellular components. The
      filamentous, heterocystous, nitrogen-fixing strains of the cyanobacterium,
      Anabaena, serve as naturally abundant contributors of nitrogen biofertilizers in
      tropical rice paddy fields. Anabaena strains are known to tolerate several
      abiotic stresses, such as heat, UV, gamma radiation, desiccation, etc., that are
      known to generate ROS. ROS are detoxified by specific antioxidant enzymes like
      superoxide dismutases (SOD), catalases and peroxiredoxins. The genome of Anabaena
      PCC7120 encodes two SODs, two catalases and seven peroxiredoxins, indicating the
      presence of an elaborate antioxidant enzymatic machinery to defend its cellular
      components from ROS. This article summarizes recent findings and depicts
      important perspectives in oxidative stress management in Anabaena PCC7120.

PMID- 24122337
TI  - Pancreatic metastasectomy: the Memorial Sloan-Kettering experience and a review
      of the literature.
AB  - Isolated pancreatic metastases may occur in patients with many types of cancer.
      Several retrospective case series have been published demonstrating the
      feasibility of resection in selected patients. Here we report our experience with
      pancreatic metastasectomy in 70 patients and review the published literature. Our
      findings suggest that long-term survival is associated with resection in selected
      patients but these outcomes must be weighed against the significant morbidity
      that is associated with pancreatic resection.

PMID- 24122338
TI  - Fan cooling of the resting area in a free stalls dairy barn.
AB  - This summer study evaluated the effect of providing additional fans (cooling) in
      the resting area within a free-stall dairy barn that had fans and sprinklers in
      the feeding area and paddock availability. Thirty cows were divided into two
      homogenous groups and kept in two pens: one had the resting area equipped with
      two fans (FAN) while no fans were added to the other resting area (CON).
      Microclimatic parameters, rectal temperature (RT), breathing rate (BR), milk
      yield, and milk pH traits were recorded. Time budgeting and the behaviour of the
      cows (time spent in the feeding area, standing and lying in other areas) were
      also recorded using digital video technology. Two slight-to-moderate heat waves
      were observed. During the hottest period the daily maximum temperature recorded
      was 33.5  degrees C and the daily maximum THI was 81.6. During this period, the
      BR and RT increased only slightly in both groups, with lower BR (n.s.) in FAN
      compared with CON. Milk yield was better maintained (n.s.) in FAN compared with
      CON during the hottest period. The FAN cows showed a greater (P<0.05) lying time
      in the free stalls (9.5 and 8.6 h/day in FAN and CON, respectively), whereas CON
      cows made greater (P<0.05) use of the paddock during evening and late evening
      hours. Consequently, the total daily lying time was 13.5 h/day in both groups. In
      conclusion, the results suggest that using fans in the resting area improves cow
      comfort, which increases use of the resting area. The lying time results also
      suggest that the benefits of providing ventilation in the resting area might be
      more evident in barns where there is no paddock.

PMID- 24122339
TI  - Periodic usage of low-protein methionine-fortified diets  in broiler chickens
      under high ambient temperature  conditions: effects on performance, slaughter
      traits, leukocyte  profiles and antibody response.
AB  - This study was performed to evaluate the effects of adding methionine supplements
      to low-protein diets and subsequent re-feeding with a normal diet on the
      productive performance, slaughter parameters, leukocyte profiles and antibody
      response in broiler chickens reared under heat stress conditions.During the whole
      experimental period (6-49 days), the birds were raised in battery cages located
      in high ambient temperature in an open-sided housing system. A total of 360 6-day
      old male chickens were divided into six treatments in six replicates with ten
      chicks each. Six isoenergetic diets, with similar total sulfur amino acids
      levels, were formulated to provide 100 and 100 (control), 85 and 100 (85S), 70
      and 100 (70S), 85 and 85 (85SG), 70 and 85 (70S85G), and 70 and 70% (70SG) of
      National Research Council recommended levels for crude protein during the starter
      (6-21 day) and grower (22-42 day) periods, respectively. Subsequently, all groups
      received a diet containing the same nutrients during the finisher period (43-49
      day). The results showed that, under heat stress conditions, average daily gain
      and feed conversion ratio and performance index from day 6 to 49, breast and
      thigh yields and antibody titer against Newcastle disease in the birds fed diets
      85S, 70S and 85SG were similar to those of birds fed control diet, whereas
      feeding diets 70S85G and 70SG significantly decreased the values of above
      mentioned parameters. Additionally, diets 85S, 70S and 85SG significantly
      decreased mortality rate and heterophil:lymphocyte ratio compared with the
      control diet. In conclusion, the results indicate that supplementation of
      methionine to diets 85S, 70S and 85SG, and then re-feeding with a conventional
      diet is an effective tool to maintain productive performance and to improve
      health indices and heat resistance in broilers under high ambient temperature
      conditions.

PMID- 24122340
TI  - Within-season flowering interruptions are common in the water-limited Sky
      Islands.
AB  - Within-season breaks in flowering have been reported in a wide range of highly
      variable ecosystems including deserts, tropical forests and high-elevation
      meadows. A tendency for interruptions in flowering has also been documented in
      southwestern US "Sky Island" plant communities, which encompass xeric to mesic
      conditions. Seasonal breaks in flowering have implications for plant reproductive
      success, population structure, and gene flow as well as resource availability for
      pollinators and dependent animals. Most reports of multiple within-season
      flowering events describe only two distinct flowering episodes. In this study, we
      set out to better quantify distinct within-season flowering events in highly
      variable Sky Islands plant communities. Across a >1,200 m elevation gradient, we
      documented a strong tendency for multiple within-season flowering events. In both
      distinct spring and summer seasons, we observed greater than two distinct within
      season flowering in more than 10 % of instances. Patterns were clearly mediated
      by the different climate factors at work in the two seasons. The spring season,
      which is influenced by both temperature and precipitation, showed a mixed
      response, with the greatest tendency for multiple flowering events occurring at
      mid-elevations and functional types varying in their responses across the
      gradient. In the summer season, during which flowering across the gradient is
      limited by localized precipitation, annual plants exhibited the fewest within
      season flowering events and herbaceous perennial plants showed the greatest.
      Additionally, more distinct events occurred at lower elevations. The patterns
      documented here provide a baseline for comparison of system responses to changing
      climate conditions.

PMID- 24122341
TI  - Body temperature and respiratory dynamics in un-shaded  beef cattle.
AB  - In this study body temperature (BT,  degrees C) and panting score (PS, 0-4.5;
      where 0 = no panting/no stress and 4.5 = catastrophic stress) data were obtained
      from 30 Angus steers housed outside over 120 days Steers were implanted with a BT
      transmitter on day -31, BT was recorded at 30-min intervals to a data logger and
      downloaded each day to a database. The cattle were housed in ten outdoor un
      shaded pens with an earthen floor, eight of which had a pen floor area of 144 m2
      (three transmitter steers plus five non-transmitter steers; 18 m2/steer) and two
      had an area of 168 m2 (three transmitter steers and six non-transmitter steers;
      18.7 m2/steer). Only data from the transmitter steers were used in this study.
      The PS of the steers was obtained daily (+/- 15 min) at 0600 hours (AM), 1200
      hours (MD) and 1600 hours (PM). At the same times climate variables (ambient
      temperature, black globe temperature, solar radiation, relative humidity, wind
      speed and rainfall) were obtained from an on-site weather station. PS
      observations were made from outside the pens so as not to influence cattle
      responses. The two closest BT values to the time when PS was obtained were
      downloaded retrospectively from a logger and averaged. A total of 8,352
      observations were used to generate second order polynomial response curves: (AM)
      y = 39.08 + 0.009 x + 0.137x2 (R2 = 0.94; P < 0.001) (MD) y = 39.09 + 0.914x -
      0.080x2 (R2 = 0.89; P < 0.001) and (PM) y = 39.52 + 0.790x - 0.068x2 (R2 = 0.83;
      P < 0.001) where y = BT ( degrees C) and  x PS. These data suggest that PS is a
      good indicator of body temperature. The BT at MD corresponded to slightly lower
      PS compared with PM, e.g., for PS 1; BT at MD = 39.1 +/- 0.05  degrees C whereas
      BT at PM = 39.5 +/- 0.05  degrees C. However during AM, BT was lower (P < 0.05)
      at PS 1, 2 and 2.5 compared with MD and PM. For example, when PS was 2.5 the BT
      at AM was 40.2 +/- 0.04  degrees C, at MD it was 40.9 +/- 0.04  degrees C and at
      PM BT was 41.1 +/- 0.04  degrees C. When PS was 0 the BT at AM and MD were
      similar. The AM response curve suggests animals attempt to increase heat
      dissipation during the cooler AM period relative to MD and PM. Morning
      observation of cattle (before feeding) are crucial for effective heat load
      management especially on days when high heat load is expected. The MD and PM
      observations provide a good indication of the impact of high environmental heat
      load on cattle. Differences in PS between AM and PM observations suggest that
      more research is needed to determine the effect of night time conditions on BT,
      PS and overall respiratory dynamics of cattle during periods of hot weather.

PMID- 24122342
TI  - The many lives of CTIP2: from AIDS to cancer and cardiac hypertrophy.
AB  - CTIP2 is a key transcriptional regulator involved in numerous physiological
      functions. Initial works have shown the importance of CTIP2 in the establishment
      and persistence of HIV latency in microglial cells, the main latent/quiescent
      viral reservoir in the brain. Recent studies have highlighted the importance of
      CTIP2 in several other pathologies, such as cardiac hypertrophy and various types
      of human malignancies. Targeting CTIP2 may therefore constitute a new approach in
      the treatment of these pathologies.

PMID- 24122343
TI  - Central Nervous System Tuberculosis: Challenges and Advances in Diagnosis and
      Treatment.
AB  - Mycobacterium tuberculosis is one of the most prevalent human infections.
      Although the largest share of the burden of disease is in Africa and Asia,
      tuberculosis has a global footprint due to travel and migration. Resource
      constraints in many low- and middle-income countries are hampering efforts to
      control new infections and to prevent drug resistance. Infection of the central
      nervous system by Mycobacterium tuberculosis includes meningitis, tuberculoma,
      and abscess and carries a high morbidity and mortality. High clinical suspicion,
      combined with cerebrospinal fluid analysis and brain imaging studies, can improve
      the diagnostic certainty. The recent scale-up of nucleic acid amplification
      technology may allow earlier diagnosis of tuberculous meningitis in many regions
      of the world. Treatment of tuberculous infection of the central nervous system is
      usually empirical and follows conventional regimens for pulmonary tuberculosis.
      The optimal treatment regimen is still being elucidated and has been the subject
      of recent clinical trials.

PMID- 24122344
TI  - The possible effect of methylphenidate on kleptomania  in a school-age girl with
      attention-deficit/hyperactivity disorder.

PMID- 24122345
TI  - Psychiatric disorders in preschoolers: the structure of DSM-IV  symptoms and
      profiles of comorbidity.
AB  - Psychiatric disorders have been increasingly recognized in preschool children; at
      present, however, we know comparatively less about how well current diagnostic
      manuals capture the symptoms described in this age group and how comorbidity is
      patterned. Therefore, this study aimed to investigate whether the symptoms
      defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition (DSM-IV) load on their respective disorders, examine whether individual
      symptoms exist that load particularly high or low on the disorder they allegedly
      define, and analyze how comorbidity clusters in individual children. Parents of a
      community sample of Norwegian 4-year-olds (N = 995) were interviewed using the
      Preschool Age Psychiatric Assessment. A confirmatory factor analysis (CFA) and a
      latent profile analysis (LPA) were performed on the symptoms of seven DSM
      disorders: attention-deficit/hyperactivity disorder (ADHD), oppositional defiant
      disorder, conduct disorder, major depressive disorder (MDD), generalized anxiety
      disorder (GAD), social phobia, and separation anxiety disorder. The results
      showed that the CFA solution that closely resembled the disorders delineated in
      the DSM-IV fitted the data best. However, vegetative symptoms did not define
      preschool depression. The LPA identified nine symptom profiles among
      preschoolers, of which four showed evidence of psychopathology: comorbid MDD/GAD
      ? ADHD combined type, comorbid MDD/GAD ? ADHD hyperactive/impulsive type,
      separation anxiety only, and social phobia only. In conclusion, the symptoms
      observed in preschoolers fit the DSM-IV well, and comorbidity followed specific
      patterns.

PMID- 24122346
TI  - Trends in stage-specific incidence rates for urothelial carcinoma of the bladder
      in the United States: 1988 to 2006.
AB  - BACKGROUND: Bladder cancer is notable for a striking heterogeneity of disease
      specific risks. Among the approximately 75% of incident cases found to be
      superficial to the muscularis propria at the time of presentation (non-muscle
      invasive bladder cancer), the risk of progression to the lethal phenotype of
      muscle-invasive disease is strongly associated with stage and grade of disease.
      Given the suggestion of an increasing percentage of low-risk cases in hospital
      based registry data in recent years, the authors hypothesized that population
      based data may reveal changes in the stage distribution of early-stage cases.
      METHODS: Surveillance, Epidemiology, and End Results (SEER) data were used to
      examine trends for the stage-specific incidence of bladder cancer between 1988
      and 2006, adjusted for age, race, and sex, using Joinpoint and nonparametric
      tests. RESULTS: The adjusted incidence rate of papillary noninvasive (Ta)
      predominantly low grade (77%) disease was found to increase from 5.52 to 9.09 per
      100,000 population (P < .0001), with an average annual percentage change of +3.3.
      Over the same period, concomitant, albeit smaller, decreases were observed for
      flat in situ (Tis) and lamina propria-invasive (T1) disease (2.57 to 1.19 and
      6.65 to 4.61 per 100,000 population [both P < .0001]; average annual percent
      change of -5.0 and -1.6, respectively). The trend was most dramatic among
      patients in the oldest age strata, suggesting a previously unappreciated cohort
      phenomenon. CONCLUSIONS: The findings of the current study should motivate
      further epidemiological investigations of differential associations of genetic
      and environmental factors with different bladder cancer phenotypes as well as
      further scrutiny of clinical practice guideline recommendations for the growing
      subgroup of predominantly older patients with lower-risk disease.

PMID- 24122347
TI  - Effect of hydrodynamics-based delivery of IL-18BP fusion gene  on rat
      experimental autoimmune myocarditis.
AB  - Interleukin-18 (IL-18) is a powerful and important cytokine in myocarditis. IL-18
      binding protein (IL-18BP), a naturally occurring antagonist of IL-18, is presumed
      to play a vital regulatory function in IL-18-mediated immune responses. The
      purpose of this study was to evaluate the alterations of IL-18 and its related
      protein expressions and the effect of hydrodynamics-based delivery of the IL-18BP
      gene for treatment of rat experimental autoimmune myocarditis (EAM).Rats were
      immunized on Day 0 and killed on 2, 3 and 4 weeks to determine IL-18 and its
      related protein expression and target cells in EAM hearts. On Day 6, rats were
      injected with a recombinant plasmid encoding IL-18BP-Ig or SP-Ig. On Day 17, rats
      were detected with echocardiography and then be killed. IL-18BP gene therapy was
      effective in controlling EAM, as monitored by a decreased ratio of heart weight
      to body weight, reduced myocarditis areas, reduced expression of atrial
      natriuretic peptide, brain natriuretic peptide, IL-17, IFN-gamma, IL-6 and IL-10.
      Furthermore, the effect of serum containing IL-18BP on the expression of immune
      relevant genes in IL-1alpha-stimulated NC cells and splenocytes cultured from EAM
      rats was examined. The results showed that IL-18BP significantly suppressed the
      expression of IL-17 as well as other proinflammatory genes such as transforming
      growth factor-beta, prostaglandin E2 synthase, cyclooxygenase-2 in IL-1alpha
      stimulated NC cells, and IL-18BP also significantly suppressed the expression of
      IL-17, IL-17R, IL-21 and IL-17-related transcriptional factor retinoic acid
      related orphan nuclear receptor, signal transducer and activator of transcription
      3 and Foxp3 in IL-1alpha-stimulated splenocytes cultured from EAM rats. IL-18 and
      its related protein played an important role on the development of EAM. IL-18BP
      effectively prevented progression of EAM by blocking IL-17 and related
      inflammatory genes expression. This might be a possible mechanism of the
      amelioration of EAM by IL-18BP treatment.

PMID- 24122348
TI  - The effect of the severity of liver cirrhosis on the level of lipids  and
      lipoproteins.
AB  - The effect of severity of liver cirrhosis, an alcoholic and non-alcoholic
      genesis, on the results of serum lipids and lipoproteins was evaluated. Serum
      cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-Ch), and
      low-density lipoprotein cholesterol (LDL-Ch) were measured in the sera of 59
      patients suffering from alcoholic cirrhosis and 34 patients with non-alcoholic
      cirrhosis. The level of serum triglycerides depends on the severity of liver
      damage in alcoholic liver cirrhosis, being the highest in Child-Pugh score B. The
      severity of liver damage significantly affects the HDL-Ch and LDL-Ch levels in
      cirrhosis of non-alcoholic origin, reaching the highest value for LDL-Ch and the
      lowest for HDL-Ch in score C. It should not be generalized that the levels of
      lipids and lipoproteins in liver cirrhosis progressively diminished with the
      deterioration of liver function. The serum HDL-Ch and LDL-Ch may be considered as
      markers of severity of liver damage in non-alcoholic cirrhosis, but the
      triglycerides only in disease of alcoholic origin.

PMID- 24122350
TI  - RFID authentication protocol to enhance patient medication safety.
AB  - Medication errors can cause substantial harm to patients. Automated patient
      medication system with RFID technology is purposely used to reduce the medication
      error, to improve the patient safety, to provide personalized patient medication
      and identification and also to provide counterfeit protection to the patients. In
      order to enhance medication safety for patients we propose a new dynamic ID based
      lightweight RFID authentication protocol. Due to low storage capacity and limited
      computational and communicational capacity of tags, only pseudo random number
      generator function, one way hash function and bitwise Xor operation are used in
      our authentication protocol. The proposed protocol is practical, secure and
      efficient for health care domain. 

PMID- 24122349
TI  - Combination therapy with thymosin alpha1 and dexamethasone helps mice survive
      sepsis.
AB  - Immune dysfunction is a major cause of mortality in septic patients. Current
      evidence indicates an important role for dendritic cells (DCs) in the
      pathophysiology of immune dysfunction, and these cells are potential targets of
      immunomodulation therapies. In the present study, our aim was to enhance the
      resistance of endotoxemic mice to bacterial translocation and secondary infection
      and to improve the outcome of these infections using a combination therapy
      consisting of thymosin alpha1 and dexamethasone in a timely manner according to
      the changes of DCs' number. The effect of treatment with dexamethasone (DXM) and
      thymosin alpha1 (Talpha1) on DCs was investigated by examining their number,
      MHCII and CD86 expression and their capacity to induce T cell activation.
      Endotoxemic mice were randomly divided into five treatment groups. The survival
      rates, the levels of TNF-alpha and IL-10, the occurrence of bacterial
      translocation, and the ability to clear secondary infections were determined.
      Additionally, the behavior of DCs over time was also evaluated. Talpha1 induced
      significant increases in DC numbers in vivo, whereas DXM reduced cell numbers
      both in vitro and in vivo. However, neither drug induced significant changes in
      the capacity of DCs to induce T cell activation or their expression of MHCII or
      CD86. Among the five treatment groups, the mice treated with a combination of DXM
      and Talpha1 had the highest survival rate; this increased survival was associated
      with a decrease in bacterial translocation to extra-intestinal organs and an
      enhanced ability to eradicate secondary infections by reversing the change in DC
      numbers during endotoxemia. Immunomodulatory therapy that combines Talpha1 and
      DXM in a timely manner and was based on changes in DCs enhanced the resistance of
      endotoxemic mice to bacterial translocation and secondary infections, improving
      the outcome of the infection. 

PMID- 24122351
TI  - Landscaping analyses of the ROC predictions of discrete-slots  and signal
      detection models of visual working memory.
AB  - A fundamental issue concerning visual working memory is whether its capacity
      limits are better characterized in terms of a limited number of discrete slots
      (DSs) or a limited amount of a shared continuous resource. Rouder et al. (2008)
      found that a mixed-attention, fixed-capacity, DS model provided the best
      explanation of behavior in a change detection task, outperforming alternative
      continuous signal detection theory (SDT) models. Here, we extend their analysis
      in two ways: first, with experiments aimed at better distinguishing between the
      predictions of the DS and SDT models, and second, using a model-based analysis
      technique called landscaping, in which the functional-form complexity of the
      models is taken into account. We find that the balance of evidence supports a DS
      account of behavior in change detection tasks but that the SDT model is best when
      the visual displays always consist of the same number of items. In our General
      Discussion section, we outline, but ultimately reject, a number of potential
      explanations for the observed pattern of results. We finish by describing future
      research that is needed to pinpoint the basis for this observed pattern of
      results.

PMID- 24122353
TI  - Pain variability and its predictors in older adults: depression, cognition,
      functional status, health, and pain.
AB  - OBJECTIVES: The purpose of this secondary data analysis is to determine whether
      depression, cognition, functional status, health, and pain severity are
      predictors of day-to-day pain variability in older adults in long-term care
      settings. METHODS: Seventy-seven adults aged 68 years and older were included in
      the multiple linear regression analyses. Pain severity mean and variability were
      measured over 30 days of daily self-reported pain levels. The Geriatric
      Depression Scale (GDS), Blessed Memory-Information-Concentration test, Physical
      Self-Maintenance Scale (PSMS), baseline pain severity, mean of daily health, and
      mean of daily pain severity were used as predictors. Pain variability was
      measured by examining intra-individual standard deviations of daily pain scores.
      RESULTS: Results show that global depression and pain severity are predictors of
      pain variability in that greater baseline depression and pain severity predicted
      higher pain variability. Daily mean pain and health were also found to be
      predictors of pain variability. DISCUSSION: Pain variability is an important
      characteristic that is not given enough emphasis in current literature.
      Understanding pain variability may give insight into older adults' experiences
      with both pain and depression, and may essentially improve quality of care and
      quality of life.

PMID- 24122355
TI  - DNA detection and cell adhesion on plasma-polymerized pyrrole.
AB  - This study investigates the application of Plasma-polymerized pyrrole (ppPY) as
      bioactive platform for DNA immobilization and cell adhesion based on the
      fundamental properties of ppPY, such as chemical structure, electrochemical
      property, and protein adsorption. Variations in electrochemical properties of the
      ppPY film deposited under different plasma conditions before and after DNA
      immobilization were measured using electrochemical impedance spectroscopy (EIS).
      The equilibrium concentration of the probe DNA immobilized on the ppPY surface
      was deduced by detecting the variations in the surface charge transfer resistance
      (Rct ) of the ppPY films after DNA immobilization with different concentrations.
      In addition, the detection limit of the target DNA hybridization with probe DNA,
      the association constant, Ka , and the dissociation constant were deduced from
      Langmuir isotherm equations simulated using the experimental data collected by
      EIS. Moreover, inverted microscope was used to observe the cell adhesions onto
      the surface of the ppPY films prepared under different plasma conditions.
      Different adhesive behaviors of cells were observed, demonstrating that ppPY
      films could be an alternative biomaterial used as the sensitive layer for DNA
      sensor or cell adhesion.

PMID- 24122352
TI  - Roles for NF-kappaB and gene targets of NF-kappaB in synaptic plasticity, memory,
      and navigation.
AB  - Although traditionally associated with immune function, the transcription factor
      nuclear factor kappa B (NF-kappaB) has garnered much attention in recent years as
      an important regulator of memory. Specifically, research has found that NF
      kappaB, localized in both neurons and glia, is activated during the induction of
      long-term potentiation (LTP), a paradigm of synaptic plasticity and correlate of
      memory. Further, experimental manipulation of NF-kappaB activation or its
      blockade results in altered memory and spatial navigation abilities. Genetic
      knockout of specific NF-kappaB subunits in mice results in memory alterations.
      Collectively, such data suggest that NF-kappaB may be a requirement for memory,
      although the direction of the response (i.e., memory enhancement or deficit) is
      inconsistent. A limited number of gene targets of NF-kappaB have been recently
      identified in neurons, including neurotrophic factors, calcium-regulating
      proteins, other transcription factors, and molecules associated with neuronal
      outgrowth and remodeling. In turn, several key molecules are activators of NF
      kappaB, including protein kinase C and [Ca(++)]i. Thus, NF-kappaB signaling is
      complex and under the regulation of numerous proteins involved in activity
      dependent synaptic plasticity. The purpose of this review is to highlight the
      literature detailing a role for NF-kappaB in synaptic plasticity, memory, and
      spatial navigation. Secondly, this review will synthesize the research evaluating
      gene targets of NF-kappaB in synaptic plasticity and memory. Although there is
      ample evidence to suggest a critical role for NF-kappaB in memory, our
      understanding of its gene targets in neurons is limited and only beginning to be
      appreciated.

PMID- 24122356
TI  - The pivotal role of microRNA-155 in the control of cancer.
AB  - microRNAs (miRNAs) are emerging as important gene expression regulators linked to
      various biological processes at a posttranscriptional level. miRNAs have been
      known to play important roles in cell proliferation, cell differentiation, and
      apoptosis. Recently, accumulate studies indicate that up-regulation of miR-155
      has been described in several types of human tumors. miR-155 has been considered
      to act as an oncogene or a tumor suppressor, depending on tumor system. Silencing
      oncomiRs or gene therapy approaches could be an effective therapeutic approach
      against tumor. Here we review the current knowledge on the functional role of miR
      155 in the control of various cancers.

PMID- 24122357
TI  - Central metabolic responses to the overproduction of fatty acids in Escherichia
      coli based on 13C-metabolic flux analysis.
AB  - We engineered a fatty acid overproducing Escherichia coli strain through
      overexpressing tesA ("pull") and fadR ("push") and knocking out fadE ("block").
      This "pull-push-block" strategy yielded 0.17 g of fatty acids (C12-C18) per gram
      of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures
      during the exponential growth phase under aerobic conditions. Metabolic fluxes
      were determined for the engineered E. coli and its control strain using tracer
      ([1,2-13C]glucose) experiments and 13C-metabolic flux analysis. Cofactor (NADPH)
      and energy (ATP) balances were also investigated for both strains based on
      estimated fluxes. Compared to the control strain, fatty acid overproduction led
      to significant metabolic responses in the central metabolism: (1) Acetic acid
      secretion flux decreased 10-fold; (2) Pentose phosphate pathway and Entner
      Doudoroff pathway fluxes increased 1.5- and 2.0-fold, respectively; (3) Biomass
      synthesis flux was reduced 1.9-fold; (4) Anaplerotic phosphoenolpyruvate
      carboxylation flux decreased 1.7-fold; (5) Transhydrogenation flux converting
      NADH to NADPH increased by 1.7-fold. Real-time quantitative RT-PCR analysis
      revealed the engineered strain increased the transcription levels of pntA
      (encoding the membrane-bound transhydrogenase) by 2.1-fold and udhA (encoding the
      soluble transhydrogenase) by 1.4-fold, which is in agreement with the increased
      transhydrogenation flux. Cofactor and energy balances analyses showed that the
      fatty acid overproducing E. coli consumed significantly higher cellular
      maintenance energy than the control strain. We discussed the strategies to future
      strain development and process improvements for fatty acid production in E. coli.

PMID- 24122358
TI  - Activation of human basophils by combined toll-like receptor- and FcepsilonRI
      triggering can promote Th2 skewing of naive T helper cells.
AB  - Basophils are mostly known for their involvement in allergic reactions. Recent
      studies in mice indicate a role for basophils in the induction of adaptive
      immunity, especially T helper 2 (Th2) responses. Therefore, it would be highly
      important to understand how basophils respond to pathogen-associated molecules,
      such as ligands for toll-like receptors (TLRs), and if the basophils could
      promote Th2 responses via these stimuli. To this end, the activation of basophils
      via TLRs in combination with activation via IgE was studied, as well as its
      effect on T helper cell skewing. Using quantitative PCR, we demonstrated the
      presence of mRNA for TLRs 1-8 in human basophils. Basophils responded to TLR
      triggering with differential cytokine production, but not with degranulation.
      Simultaneous triggering of TLRs and IgE led to synergy in production of IL-4, IL
      8, IL-13, and RANTES. Furthermore, the synergistic effects on basophils mediated
      by IgE and TLR-4 triggering allowed robust Th2 skewing upon activation of naive
      human CD4+ T cells. Our data show that human basophils respond to TLR ligands in
      synergy with IgE-mediated activation and that the cytokines produced can promote
      Th2 differentiation. These results indicate a role for basophils in the
      regulation of T-cell responses in humans.

PMID- 24122360
TI  - Society of Gastrointestinal Endoscopy of India.

PMID- 24122359
TI  - Purification and characterization of a novel extracellular halophilic and organic
      solvent-tolerant amylopullulanase from the haloarchaeon, Halorubrum sp. strain
      Ha25.
AB  - A halophilic archaeon, Halorubrum sp. strain Ha25, produced extracellular
      halophilic organic solvent-tolerant amylopullulanase. The maximum enzyme
      production was at high salt concentration, 3-4 M NaCl. Optimum pH and temperature
      for enzyme production were 7.0 and 40  degrees C, respectively. Molecular mass of
      purified enzyme was estimated to be about 140 kDa by SDS-PAGE. This enzyme was
      active on pullulan and starch as substrates. The apparent Km for the enzyme
      activity on pullulan was 4 mg/ml and for soluble starch was 1.8 mg/ml. Optimum
      temperature for amylolytic and pullulytic activities was 50  degrees C. Optimum
      pH for amylolytic activity was 7 and for pullulytic activity was 7.5. This enzyme
      was active over a wide range of concentrations (0-4.5 M) of NaCl. The effect of
      organic solvents on the enzyme activities showed that this enzyme was more stable
      in the presence of non-polar organic solvents than polar solvents. This study is
      the first report on amylopullulanase production in halophilic bacteria and
      archaea.

PMID- 24122361
TI  - Underutilization of radiation therapy in patients with glioblastoma: predictive
      factors and outcomes.
AB  - BACKGROUND: Randomized trials have demonstrated that radiation improves survival
      in patients with glioblastoma. The purpose of this study was to characterize the
      risk factors and impact of omission of radiation therapy in such patients.
      METHODS: The Surveillance, Epidemiology, and End Results (SEER) program was used
      to identify 22,777 patients diagnosed with glioblastoma between 1988 and 2007.
      Multivariable logistic regression was employed to identify predictors associated
      with omission of radiation. Cox regression was used to characterize the impact of
      omitting radiation on all-cause mortality. RESULTS: Among the entire cohort,
      16,863 of 22,777 patients (74%) received radiation, whereas 5914 of 22,777
      patients (26%) did not. Factors associated with omission of radiation included
      older age (OR=1.048 per year increase, 95% CI=1.046-1.051, P<.001), lower annual
      income (OR=0.93 per $10,000 increase, 95% CI=0.90-0.96, P<.001), African American
      race (reference=white, OR=1.19, 95% CI=1.03-1.37, P=.02), Hispanic race (OR=1.34,
      95% CI=1.19-1.50, P< .001), Asian American race (OR=1.24, 95% CI=1.04-1.48,
      P<.001), unmarried status (OR=1.71, 95% CI=1.60-1.83, P< .001), and subtotal
      resection/biopsy (OR=1.82, 95% CI=1.69-1.96, P<.001). The use of radiation was
      significantly associated with improved overall survival (2-year survival: 14.6%
      versus 4.2%, P<.001; adjusted HR=2.09, 95% CI=2.02-2.16, P<.001). When the
      population was restricted to patients <50 years old, these findings remained
      largely unchanged. CONCLUSIONS: Radiation therapy is associated with survival
      benefit in patients with glioblastoma, and sociodemographic factors play a
      significant role in the underutilization of radiation. The underlying causes for
      these disparities in care require further research.

PMID- 24122362
TI  - Distinguishing lexical- versus discourse-level processing using event-related
      potentials.
AB  - Two experiments examine the links between neural patterns in EEG (e.g., N400s,
      P600s) and their corresponding cognitive processes (e.g., lexical access,
      discourse integration) by varying the lexical and syntactic contexts of co
      referential expressions. Experiment 1 examined coreferring expressions when they
      occurred within the same clause as their antecedents (John/Bill warmly dressed
      John). Experiment 2 examined between-clause co-referencing with expressions that
      also varied in lexical frequency (John/Weston went to the store so that
      John/Weston could buy milk). Evidence of facilitated lexical processing occurred
      after repeated names, which elicited smaller N400s, as compared with new names.
      N400s were also attenuated to a greater degree for low-frequency expressions than
      for high-frequency ones. Repeated names also triggered evidence of postlexical
      processing, but this emerged as larger P600s for within-clause co-referencing and
      delayed N400s for between-clause co-referencing. Together, these results suggest
      that linguistic processes can be distinguished through distinct ERP components or
      distinct temporal patterns.

PMID- 24122363
TI  - Protection of dopaminergic neurons in a mouse model of Parkinson's disease by a
      physically-modified saline containing charge-stabilized nanobubbles.
AB  - Neuroinflammation underlies the pathogenesis of various neurodegenerative
      disorders including Parkinson's disease (PD). Despite intense investigations, no
      effective therapy is available to stop its onset or halt its progression. RNS60
      is a novel therapeutic containing charge-stabilized nanobubbles in saline,
      generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under
      elevated oxygen pressure. Recently, we have delineated that RNS60 inhibits the
      expression of proinflammatory molecules in glial cells via type 1A
      phosphatidylinositol-3 kinase (PI3K)-mediated upregulation of IkappaBalpha. In
      this study, we demonstrate that RNS60 inhibited the expression of proinflammatory
      molecules in cultured microglial cells stimulated by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridium ion (MPP(+)) and in vivo in the nigra of MPTP-intoxicated
      mice. While investigating the underlying mechanisms, we found that MPTP
      intoxication rapidly stimulated the activation of type IB PI3K p110gamma in the
      nigra, while suppressing the activation of type IA PI3K p110alpha/beta.
      Interestingly, RNS60 treatment suppressed the activation of p110gamma PI3K, while
      inducing the activation of p110alpha/beta PI3K in the nigra of MPTP-intoxicated
      mice. Accordingly, RNS60 treatment increased the level of IkappaBalpha and
      inhibited the activation of NF-kappaB in the SNpc of MPTP-intoxicated mice. These
      findings paralleled dopaminergic neuronal protection, normalized striatal
      neurotransmitters, and improved motor functions in MPTP-intoxicated mice. These
      results strongly suggest a promising therapeutic role of this simple modified
      saline in PD and other neuroinflammatory disorders.

PMID- 24122364
TI  - Between two beds: inappropriately delayed discharges from hospitals.
AB  - Acknowledging the necessity of a division of labour between hospitals and social
      care services regarding treatment and care of patients with chronic and complex
      conditions, is to acknowledge the potential conflict of interests between health
      care providers. A potentially important conflict is that hospitals prefer
      comparatively short length of stay (LOS) at hospital, while social care services
      prefer longer LOS all else equal. Furthermore, inappropriately delayed discharges
      from hospital, i.e. bed blocking, is costly for society. Our aim is to discuss
      which factors that may influence bed blocking and to quantify bed blocking costs
      using individual Norwegian patient data, merged with social care and hospital
      data. The data allow us to divide hospital LOS into length of appropriate stay
      (LAS) and length of delay (LOD), the bed blocking period. We find that additional
      resources allocated to social care services contribute to shorten LOD indicating
      that social care services may exploit hospital resources as a buffer for
      insufficient capacity. LAS increases as medical complexity increases indicating
      hospitals incentives to reduce LOS are softened by considerations related to
      patients' medical needs. Bed blocking costs constitute a relatively large share
      of the total costs of inpatient care.

PMID- 24122366
TI  - Invited address: Street killings: prediction of homicide offenders and their
      victims.
AB  - The article reports on childhood predictors (explanatory, behavioral and
      offenses) to predict homicide offenders in the longitudinal Pittsburgh Youth
      Study, and compares these predictors with predictors of homicide victims in the
      same study. This forms the basis for formulating antecedents that are shared
      between homicide offenders and homicide victims at a young age (ages 7-11) and
      antecedents that are not shared or are unique for each. Implications of the
      research are highlighted for early intervention and for interventions with high
      risk offenders.

PMID- 24122367
TI  - Temporal dynamics of changes in reactive oxygen species (ROS) levels and cellular
      morphology are coordinated during complementary chromatic acclimation in
      Fremyella diplosiphon.
AB  - Fremyella diplosiphon alters the phycobiliprotein composition of its light
      harvesting complexes, i.e., phycobilisomes, and its cellular morphology in
      response to changes in the prevalent wavelengths of light in the external
      environment in a phenomenon known as complementary chromatic acclimation (CCA).
      The organism primarily responds to red light (RL) and green light (GL) during CCA
      to maximize light absorption for supporting optimal photosynthetic efficiency.
      Recently, we found that RL-characteristic spherical cell morphology is associated
      with higher levels of reactive oxygen species (ROS) compared to growth under GL
      where lower ROS levels and rectangular cell shape are observed. The RL-dependent
      association of increased ROS levels with cellular morphology was demonstrated by
      treating cells with a ROS-scavenging antioxidant which resulted in the
      observation of GL-characteristic rectangular morphology under RL. To gain
      additional insights into the involvement of ROS in impacting cellular morphology
      changes during CCA, we conducted experiments to study the temporal dynamics of
      changes in ROS levels and cellular morphology during transition to growth under
      RL or GL. Alterations in ROS levels and cell morphology were found to be
      correlated with each other at early stages of acclimation of low white light
      grown cells to growth under high RL or cells transitioned between growth in RL
      and GL. These results provide further general evidence that significant RL
      dependent increases in ROS levels are temporally correlated with changes in
      morphology toward spherical. Future studies will explore the light-dependent
      mechanisms by which ROS levels may be regulated and the direct impacts of ROS on
      the observed morphology changes.

PMID- 24122368
TI  - Give me a sign: decoding complex coordinated hand movements using high-field
      fMRI.
AB  - Decoding movements from the human cortex has been a topic of great interest for
      controlling an artificial limb in non-human primates and severely paralyzed
      people. Here we investigate feasibility of decoding gestures from the
      sensorimotor cortex in humans, using 7 T fMRI. Twelve healthy volunteers
      performed four hand gestures from the American Sign Language Alphabet. These
      gestures were performed in a rapid event related design used to establish the
      classifier and a slow event-related design, used to test the classifier. Single
      trial patterns were classified using a pattern-correlation classifier. The four
      hand gestures could be classified with an average accuracy of 63 % (range 35-95
      %), which was significantly above chance (25 %). The hand region was, as
      expected, the most active region, and the optimal volume for classification was
      on average about 200 voxels, although this varied considerably across
      individuals. Importantly, classification accuracy correlated significantly with
      consistency of gesture execution. The results of our study demonstrate that
      decoding gestures from the hand region of the sensorimotor cortex using 7 T fMRI
      can reach very high accuracy, provided that gestures are executed in a consistent
      manner. Our results further indicate that the neuronal representation of hand
      gestures is robust and highly reproducible. Given that the most active foci were
      located in the hand region, and that 7 T fMRI has been shown to agree with
      electrocorticography, our results suggest that this confined region could serve
      to decode sign language gestures for intracranial brain-computer interfacing
      using surface grids.

PMID- 24122369
TI  - CNS Mold Infections.
AB  - Mold infections of the central nervous system (CNS) present as abscesses,
      infarcts, hemorrhages, and, less commonly, meningitis. These invasive infections
      are difficult both to identify and to eradicate given low-sensitivity diagnostics
      and high-toxicity, low-efficacy antifungal therapies, hence resulting in high
      rates of morbidity and mortality. Herein, the recent literature on CNS mold
      infections is reviewed, and updates in diagnosis and management are discussed.

PMID- 24122370
TI  - A new method for evaluating flowering synchrony to support the temporal isolation
      of genetically modified crops from their wild relatives.
AB  - Hybridization between crops and their wild relatives potentially threatens the
      genetic identity of the wild plants, particularly in the case of genetically
      modified crops. Only a few studies have examined the use of temporal isolation to
      prevent hybridization, and the indices used in those studies, (e.g., the days of
      flowering overlap), are not precise to evaluate the degree of synchrony in
      flowering. Here we propose a flowering similarity index that can compare the
      degree of flowering synchrony between two relevant species and measure the
      efficiency of temporal isolation. The results showed that the flowering
      similarity index predicts the likelihood of hybridization much better than the
      number of flowering-overlap days, regardless of different flowering patterns
      among cultivars. Thus, temporal isolation of flowering or flowering asynchrony is
      the most effective means in preventing hybridization between crops and their wild
      relatives. 

PMID- 24122371
TI  - Surgical management of non-colorectal hepatic metastasis.
AB  - Isolated hepatic metastases from non-colorectal primary tumors are rare. Patients
      with neuroendocrine tumors have an indolent biology compared with other non
      colorectal histologies. This article discusses the surgical management options
      for patients with neuroendocrine liver metastases and, separately, for those with
      non-colorectal, non-neuroendocrine metastases. Emphasis is placed on the
      importance of patient selection, understanding the tumor biology and response to
      systemic therapy.

PMID- 24122372
TI  - In brief: Notch signalling in health and disease.
AB  - The Notch pathway controls many aspects of development and is mutated in various
      human cancers. Remarkably, Notch function changes during the development of
      cellular hierarchies and can be either oncogenic or tumour-suppressive, depending
      on cellular context. Notch dysregulation is also important in cardiovascular
      disease and disorders of immunity. This mini-review outlines key features of the
      Notch signalling pathway and emerging data linking it to human diseases.

PMID- 24122375
TI  - Downregulation of microRNA-15b by hepatitis B virus X enhances hepatocellular
      carcinoma proliferation via fucosyltransferase 2-induced Globo H expression.
AB  - Globo H, a cancer-associated carbohydrate antigen, is highly expressed in various
      types of cancers. However, the role of Globo H in hepatocellular carcinoma (HCC)
      remains elusive. In our study, we performed glycan microarray analysis of 134
      human serum samples to explore anti-Globo H antibody changes and found that Globo
      H is upregulated in hepatitis B virus (HBV)-positive HCC. Similarly,
      immunohistochemistry showed that Globo H expression was higher in tumors compared
      to normal tissues. In addition, fucosyltransferase 2 (FUT2), the main synthetic
      enzyme of Globo H, was also increased in HCC cells overexpressing HBV X protein
      (HBX). HBX plays an important role in promoting cell proliferation and may be
      related to increased levels of FUT2 and Globo H. Furthermore, using microRNA
      profiling, we observed that microRNA-15b (miR-15b) was downregulated in patients
      with HCC and confirmed association of FUT2 expression with expression of its
      product, Globo H. Therefore, our results suggest that HBX suppressed the
      expression of miR-15b, which directly targeted FUT2 and then increased levels of
      Globo H to enhance HCC cell proliferation. Additionally, proliferation of HBX
      overexpressing HCC cells was significantly inhibited by treatment with Globo H
      antibody in vitro. In xenograft animal experiments, we found that overexpression
      of miR-15b effectively suppressed tumor growth. The newly identified HBX/miR
      15b/FUT2/Globo H axis suggests one possible molecular mechanism of HCC cell
      proliferation and represents a new potential therapeutic target for HCC
      treatment. 

PMID- 24122374
TI  - Infant and toddler crying, sleeping and feeding problems and trajectories of
      dysregulated behavior across childhood.
AB  - Infant and toddler regulatory problems (RPs) including crying, sleeping and
      feeding, are a frequent concern for parents and have been associated with
      negative behavioral outcomes in early and middle childhood. Uncertain is whether
      infant and toddler RPs predict stable, trait-like dysregulated behavior across
      childhood. We addressed this gap in the literature using data from the Avon
      Longitudinal Study of Parents and Children (ALSPAC). RPs at 6, 15-18, & 24-30
      months and childhood dysregulated behavior at 4, 7, 8, & 9.5 years were assessed
      using mother report. Latent Class Growth Analysis (LCGA) indicated that
      trajectories of childhood dysregulated behavior were stable over time. All single
      RPs (i.e., crying, sleeping & feeding problems) were significantly associated
      with childhood dysregulated behavior. For example, crying problems at 6 months
      after controlling for confounders (Odds Ratios; 95% Confidence Intervals):
      Moderate dysregulated behavior: OR = 1.50, 95% CI [1.09 to 2.06], high
      dysregulated behavior: OR = 2.13, 95% CI [1.49 to 3.05] and very high
      dysregulated behavior: OR = 2.85, 95% CI [1.64 to 4.94]. Multiple RPs were
      especially strongly associated with dysregulated behavior. For example, the RP
      composite at 15-18 months: 1 RP, very high dysregulated behavior: OR = 2.79, 95%
      CI [2.17 to 3.57], 2 RPs, very high dysregulated behavior: OR = 3.46, 95% CI
      [2.38 to 5.01], 3 RPs, very high dysregulated behavior: OR = 12.57, 95% CI [6.38
      to 24.74]. These findings suggest that RPs in infants and toddlers predict stable
      dysregulated behavior trajectories across childhood. Interventions for early RPs
      could help prevent the development of chronic, highly dysregulated behavior.

PMID- 24122376
TI  - [Impact of implementation strategies on adherence rates to colorectal cancer
      (CRC) guidelines after polypectomy in a university hospital].
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most common malignancy in
      Germany. Screening colonoscopies with polypectomy have been demonstrated to
      reduce the incidence of CRC. Detailed recommendations on scheduling screening and
      follow-up colonoscopies have therefore been included into national guidelines.
      Knowledge about CRC guidelines and adherence to guideline recommendations varies
      greatly among physicians. METHODS: We combined different implementation
      strategies (training courses, case discussion, handouts, wall charts) to improve
      adherence of recommendations for scheduling follow-up colonoscopy. To assess
      adherence, written recommendations given at discharge after inpatient treatment
      for polypectomy were analysed before (n = 111) and after (n = 83) the
      implementation of the above-mentioned implementation measures. Additional factors
      possibly influencing the recommendations of physicians were collected (histology,
      polyp size). RESULTS: The adherence to the CRC guideline before implementation of
      the above-mentioned measures was moderate. After intervention, there was a non
      significant increase from 47 % to 53 %. Senior physician review and editing of
      the discharge summaries improved guideline adherence of recommendations to 69 %.
      Neither the education level of residents nor their affiliation to a certain
      department had an impact on the quality of the recommendations. Histology and in
      particular information on the resection status of the polyps in the pathology
      report (complete versus incomplete resection) had an influence of the recommended
      schedule. Furthermore, size of the polyps, but not the number, had a
      statistically significant influence on the quality of the recommendations.
      CONCLUSIONS: The inadequate improvement of guideline adherence can possibly be
      explained by the insufficient interactive and repetitive character of
      interventions. As the histology reports seem to have an influence on the
      recommendations in regards to the interval to the next colonoscopy,
      interdisciplinary teaching is necessary to improve guideline concurrent care.

PMID- 24122377
TI  - Pancreas mobile.
AB  - BACKGROUND AND AIM: Up to now, little is known about the mobility of the pancreas
      due to changes in posture. The present study was conducted to assess the position
      of the pancreas in the left recumbent posture (endoscopy posture), the pancreatic
      mobility during changes of the posture from supine to endoscopy posture and also
      evaluates the possible factors associated with pancreatic mobility. METHODS: 199
      patients with (68) or without chronic pancreatitis were examined using
      conventional gray-scale transabdominal ultrasound to image the position and
      mobility of the pancreatic head with reference to the vertebral spine and aorta
      in the supine and left recumbent position. In a subgroup of 75 consecutive
      healthy subjects regarding the pancreas, the exact moving distance of the central
      line of the pancreatic head from the supine to left recumbent position was
      obtained regarding the central line of the spine as the reference. Besides the
      199 patients, 50 patients without pancreatic pathology were evaluated by
      endoscopic ultrasound with radial transducers. RESULTS: On conventional
      ultrasound in supine (left lateral) position the percentage of patients with
      right-aortal, pre-aortal, left-aortal pancreatic head were 91.0 % (49 %), 8.0 %
      (31 %) and 1.0 % (20 %), respectively. Significant movement of the pancreatic
      head in relation to the aorta was observed in 48 % of patients. The moving
      distance was correlated to the age, sex and the presence of chronic pancreatitis.
      Pancreas mobility was more pronounced in young healthy females. No association
      was found between the moving distance and the body mass index (BMI) and splenic
      size. On endoscopic ultrasound, the orientation of the pancreas with a view of
      more (or equal) than 180o was observed in 48 % and less than 180o in 52 % of
      patients. CONCLUSION: Pancreas mobile is a common phenomenon (about 50 %) which
      has not often been recognized in daily routine. This phenomenon is more likely in
      healthy young females. This knowledge might be of importance for improved
      interpretation of endoscopic ultrasound imaging examinations in patients with and
      without peripancreatic infiltration.

PMID- 24122378
TI  - [Validation of the IBS-SSS].
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder
      characterised by abdominal pain, associated with stool abnormalities and changes
      in stool consistency. Diagnosis of IBS is based on characteristic symptoms and
      exclusion of other gastrointestinal diseases. A number of questionnaires exist to
      assist diagnosis and assessment of severity of the disease. One of these is the
      irritable bowel syndrome - severity scoring system (IBS-SSS). The IBS-SSS was
      validated 1997 in its English version. In the present study, the IBS-SSS has been
      validated in German language. To do this, a cohort of 60 patients with IBS
      according to the Rome III criteria, was compared with a control group of healthy
      individuals (n = 38). We studied sensitivity and reproducibility of the score, as
      well as the sensitivity to detect changes of symptom severity. The results of the
      German validation largely reflect the results of the English validation. The
      German version of the IBS-SSS is also a valid, meaningful and reproducible
      questionnaire with a high sensitivity to assess changes in symptom severity,
      especially in IBS patients with moderate symptoms. It is unclear if the IBS-SSS
      is also a valid questionnaire in IBS patients with severe symptoms because this
      group of patients was not studied. 

PMID- 24122379
TI  - Development of miliary tuberculosis under infliximab in a patient with
      spondyloarthritis and suspected Crohn's disease.
AB  - Tuberculosis (TB) infection is a major concern in patients with chronic
      autoimmune conditions under immunosuppressive therapy. Gastrointestinal
      tuberculosis can be misdiagnosed as Crohn's disease with detrimental consequences
      for the patient. We report on a 40-year old ethnic Turkish patient with HLA-B27
      positive spondyloarthritis who developed gastrointestinal symptoms under
      immunosuppressive treatment with infliximab. Crohn's disease was diagnosed at a
      primary care hospital and immunosuppressive treatment was escalated. Initial
      diagnostic tests for tuberculosis were negative. When the clinical condition
      deteriorated, the patient was transferred to our intensive care unit for further
      diagnosis and treatment. Tuberculosis was suspected due to clinical presentation
      and radiological signs and anti-tuberculous treatment was initiated. After the
      onset of treatment, first microbiological results confirmed the diagnosis of
      miliary TB with Mycobacterium bovis. As an infection route we assume primary
      gastrointestinal infection with M. bovis during the patient's annual holidays in
      Turkey with a rapid development of miliary TB under infliximab and escalated
      immunosuppressive therapy. This case report demonstrates the difficulties in
      differentiating intestinal TB from other granulomatous conditions such as Crohn's
      disease. The diagnostic tools for gastrointestinal tuberculosis are discussed in
      detail regarding their sensitivity, specificity as well as positive and negative
      predictive values. 

PMID- 24122380
TI  - Cholesteryl ester storage disease: an easily missed diagnosis in oligosymptomatic
      children.
AB  - Cholesteryl ester storage disease (CESD) is a rare, autosomal recessively
      inherited disorder resulting from deficient activity of lysosomal acid lipase
      (LAL). LAL is the key enzyme hydrolyzing cholesteryl esters and triglycerides
      stored in lysosomes after LDL receptor-mediated endocytosis. Mutations within the
      LIPA gene locus on chromosome 10q23.2-q23.3 may result either in the always fatal
      Wolman disease, where no LAL activity is found, or in the more benign disorder
      CESD with a reduced enzymatic activity, leading to massive accumulation of
      cholesteryl esters and triglycerides in many body tissues. CESD affects mostly
      the liver, the spectrum is ranging from isolated hepatomegaly to liver cirrhosis.
      Chronic diarrhea has been reported in some pediatric cases, while calcifications
      of the adrenal glands, the hallmark of Wolman disease, are rarely observed.
      Hypercholesterolemia and premature atherosclerosis are other typical disease
      manifestations. Hepatomegaly as a key finding has been reported in all 71
      pediatric patients and in 134 of 135 adult cases in the literature. We present a
      13-year-old boy with mildly elevated liver enzymes in the absence of
      hepatomegaly, finally diagnosed with CESD. Under pravastatine treatment, the
      patient has normal laboratory findings and is clinically unremarkable since 5
      years of follow-up. To our knowledge, this is the first pediatric case of
      genetically and biopsy confirmed CESD without hepatomegaly, suggesting that this
      diagnosis can be easily missed. It further raises the question about the natural
      course and the therapy required for this oligosymptomatic form. 

PMID- 24122381
TI  - [Bleeding plug obstructing the pylorus - a rare complication of a gastric
      lipoma].
AB  - A 67-year-old patient was admitted to our hospital with lack of appetite and
      upper gastrointestinal bleeding. The immediately performed emergency gastroscopy
      showed a giant subepithelial tumour with ulceration located in the antrum.
      Emerging from the tumourous ulcer was a peg-shaped outgrowth reaching through the
      pylorus down to the duodenum causing gastric outlet obstruction. Based on this
      unusual presentation of a gastric giant lipoma we have reviewed the literature
      concerning differential diagnosis and treatment options. 

PMID- 24122382
TI  - [Role of MARS(r) dialysis in acute-on-chronic liver failure].

PMID- 24122383
TI  - [News on Azathioprine in IBD].

PMID- 24122384
TI  - Citation analysis of Canadian psycho-oncology and supportive care researchers.
AB  - PURPOSE: The purpose of this study was to conduct a historical review of psycho
      oncology and supportive care research in Canada using citation analysis and to
      review the clinical impact of the research conducted by the most highly cited
      researchers. METHODS: The lifetime journal publication records of 109 psycho
      oncology and supportive care researchers in Canada were subject to citation
      analysis using the Scopus database, based on citations since 1996 of articles
      deemed relevant to psychosocial oncology and supportive care, excluding self
      citations. Three primary types of analysis were performed for each individual:
      the number of citations for each journal publication, a summative citation count
      of all published articles, and the Scopus h-index. RESULTS: The top 20 psycho
      oncology/supportive care researchers for each of five citation categories are
      presented: the number of citations for all publications; the number of citations
      for first-authored publications; the most highly cited first-authored
      publications; the Scopus h-index for all publications; and the Scopus h-index for
      first-authored publications. The three most highly cited Canadian psycho-oncology
      researchers are Dr. Kerry Courneya (University of Alberta), Dr. Lesley Degner,
      (University of Manitoba), and Dr. Harvey Chochinov (University of Manitoba).
      CONCLUSIONS: Citation analysis is useful for examining the research performance
      of psycho-oncology and supportive care researchers and identifying leaders among
      them.

PMID- 24122385
TI  - Predictors of falls among community-dwelling older adults with cancer: results
      from the health and retirement study.
AB  - PURPOSE: Cancer symptoms and the side effects of its treatment can increase the
      risk of falling among older adults with cancer. This study aimed to identify
      predictors of falling and recurrent falls among community-dwelling older adults
      with cancer over a 2-year period. METHODS: Data from the Health and Retirement
      Study were used (N = 1,630) in this study. The sample had a mean age of 75 years
      and was mostly female (53 %) and white (89 %). Descriptive analyses, correlation
      analyses, and logistic regressions were used to analyze the data. RESULTS: The
      results showed that functional limitations (OR = 1.13, 95 % CI = 1.03-1.24), the
      full-tandem stance (OR = 1.48, 95 % CI = 1.01-2.16), and self-reported
      difficulties with balance (OR = 1.50, 95 % CI = 1.23-1.83) at time 1 were
      significant predictors of falling at time 2. Only difficulties with self-reported
      balance (OR = 1.84, 95 % CI = 1.44-2.36) at time 1 were found to be a predictor
      of recurrent falls at time 2. CONCLUSIONS: The consequences of falling can
      complicate the course of cancer treatment. Measures of functional limitations and
      balance have the potential to be quick and useful clinical tools to detect
      falling among seniors with cancer living in communities.

PMID- 24122386
TI  - Mental health professionals' natural taxonomies of mental disorders: implications
      for the clinical utility of the ICD-11 and the DSM-5.
AB  - OBJECTIVE: To examine the conceptualizations held by psychiatrists and
      psychologists around the world of the relationships among mental disorders in
      order to inform decisions about the structure of the classification of mental and
      behavioral disorders in World Health Organization's International Classification
      of Diseases and Related Health Problems 11th Revision (ICD-11). METHOD: 517
      mental health professionals in 8 countries sorted 60 cards containing the names
      of mental disorders into groups of similar disorders, and then formed a
      hierarchical structure by aggregating and disaggregating these groupings.
      Distance matrices were created from the sorting data and used in cluster and
      correlation analyses. RESULTS: Clinicians' taxonomies were rational,
      interpretable, and extremely stable across countries, diagnostic system used, and
      profession. Clinicians' consensus classification structure was different from ICD
      10 and the American Psychiatric Association's Diagnostic and Statistical Manual
      of Mental Disorders 4th Edition (DSM-IV), but in many respects consistent with
      ICD-11 proposals. CONCLUSIONS: The clinical utility of the ICD-11 may be improved
      by making its structure more compatible with the common conceptual organization
      of mental disorders observed across diverse global clinicians.

PMID- 24122387
TI  - Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable
      responses in rituximab-resistant indolent and mantle cell lymphomas.
AB  - BACKGROUND: Lenalidomide is an immunomodulatory drug with effects on the immune
      system that may enhance antibody-dependent cell-mediated cytotoxicity and reverse
      tumor-induced immune suppression. Furthermore, single-agent lenalidomide has
      therapeutic activity in relapsed/refractory B-cell lymphomas. These immunologic
      effects potentially may enhance the action of rituximab. METHODS: To test the
      efficacy of lenalidomide combined with rituximab, the authors conducted a phase 2
      trial of lenalidomide, low-dose dexamethasone, and rituximab in patients who had
      rituximab-resistant, relapsed/refractory, indolent B-cell or mantle cell
      lymphomas. Patients received two 28-day treatment cycles of lenalidomide 10 mg
      daily and dexamethasone 8 mg once weekly (part I). During cycle 3, 4 weekly doses
      of rituximab 375 mg/m2 were administered with lenalidomide-dexamethasone (part
      II). After the part II response assessment, stable or responding patients
      continued to receive lenalidomide-dexamethasone. RESULTS: Twenty-seven patients
      with follicular (n=18), mantle cell (n=5), small lymphocytic (n=3), and marginal
      zone (n=1) lymphomas started therapy; 3 of 27 patients discontinued therapy
      because of adverse events and were not evaluable for response. For 24 patients,
      the overall response rate after part I was 29% (4 patients had a complete
      response [CR] or CR unconfirmed, and 3 patients had a partial response), and the
      overall response rate after part II was 58% (8 patients had a CR, and 6 patients
      had a partial response). For 27 patients, at a median follow-up of 12.2 months,
      the median progression-free survival was 23.7 months. CONCLUSIONS: The
      combination of lenalidomide, low-dose dexamethasone, and rituximab achieved high
      response rates with durable responses in patients with rituximab-resistant,
      indolent B-cell and mantle cell lymphomas. Overall response rate increased from
      29% after two 28-day cycles of lenalidomide and low-dose dexamethasone to 58%
      after the addition of rituximab, suggesting that lenalidomide can overcome
      resistance to rituximab.

PMID- 24122388
TI  - Simultaneous method for analyzing dimerization and signaling of G-protein-coupled
      receptor in yeast by dual-color reporter system.
AB  - Understanding the role of G-protein-coupled receptor (GPCR) dimerization in
      cellular function has now become a major research focus. The potentially large
      functional and physiological diversity of dimerization among GPCRs is expected to
      provide opportunities for novel drug discovery. However, there is currently a
      lack of cell-based assays capable of specific profiling for the functional
      consequences of dimerization linked to ligand-mediated signaling. Here, we
      present an advanced method to simultaneously analyze the dimerization and ligand
      response of GPCRs using two yeast-based systems for split-ubiquitin two-hybrid
      assay and G-protein signaling assay. To permit simultaneous detection, we
      established a two-color (dualcolor) fluorescence reporter gene assay using
      enhanced green fluorescent protein (EGFP) and a far-red derivative of the
      tetrameric fluorescent protein DsRed-Express2 (E2-Crimson). In the present study,
      we tested our method first by analyzing dimerization and ligand-mediated
      signaling by the yeast endogenous pheromone receptor (Ste2p). Second, we showed
      that the system facilitated mutational analysis of domains involved in
      dimerization and signaling by Ste2p. Third, we successfully demonstrated that the
      system could simultaneously monitor homo- and hetero-dimerization and
      somatostatin-induced signaling in the test case of the human SSTR5 somatostatin
      receptor. Our strategy is expected to provide a useful tool for the elucidation
      of molecular biological functions of GPCR dimers and for the screening of GPCR
      dimer-specific agonistic ligands.

PMID- 24122389
TI  - Randomized trial of preoperative docetaxel with or without capecitabine after 4
      cycles of 5-fluorouracil- epirubicin-cyclophosphamide (FEC) in early-stage breast
      cancer: exploratory analyses identify Ki67 as a predictive biomarker for response
      to neoadjuvant chemotherapy.
AB  - This randomized, multicenter study compared the efficacy of docetaxel with or
      without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC)
      therapy in operable breast cancer and investigated the role of Ki67 as a
      predictive biomarker. Patients were randomized to 4 cycles of
      docetaxel/capecitabine (docetaxel: 75 mg/m2 on day 1; capecitabine: 1,650 mg/m2
      on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m2 on day 1 every 3 weeks)
      after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100
      mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The primary
      endpoint was the pathological complete response (pCR) rate. Predictive factor
      analysis was conducted using clinicopathological markers, including hormone
      receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were
      randomized; the overall response in the docetaxel/capecitabine and docetaxel
      groups was 88.3 and 87.4 %, respectively. There were no significant differences
      in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748),
      disease-free survival, or overall survival. However, patients with mid-range
      Ki67LI (10-20 %) showed a trend towards improved pCR rate with
      docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate
      logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 %
      CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this
      neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did
      not generate significant improvement in pCR compared to docetaxel alone. However,
      exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a
      useful tool in the identification of responders to preoperative
      docetaxel/capecitabine in early-stage breast cancer.

PMID- 24122390
TI  - Impact of body mass index and weight fluctuation on lymphedema risk in patients
      treated for breast cancer.
AB  - Identifying risk factors for lymphedema in patients treated for breast cancer has
      become increasingly important, given the current lack of standardization
      surrounding diagnosis and treatment. Reports on the association of body mass
      index (BMI) and weight change with lymphedema risk are conflicting. We sought to
      examine the impact of pre-operative BMI and post-treatment weight change on the
      incidence of lymphedema. From 2005 to 2011, 787 newly diagnosed breast cancer
      patients underwent prospective arm volume measurements with a Perometer pre- and
      post-operatively. BMI was calculated from same-day weight and height
      measurements. Lymphedema was defined as a relative volume change (RVC) of >= 10
      %. Univariate and multivariate Cox proportional hazards models were used to
      evaluate the association between lymphedema risk and pre-operative BMI, weight
      change, and other demographic and treatment factors. By multivariate analysis, a
      pre-operative BMI >= 30 was significantly associated with an increased risk of
      lymphedema compared to a pre-operative BMI <25 and 25- <30 (p = 0.001 and p =
      0.012, respectively). Patients with a pre-operative BMI 25- <30 were not at an
      increased risk of lymphedema compared to patients with a pre-operative BMI <25 (p
      = 0.409). Furthermore, a cumulative absolute weight fluctuation of 10 pounds
      gained/lost per month post-operatively significantly increased risk of lymphedema
      (HR: 1.97, p = < 0.0001). In conclusion, pre-operative BMI of >= 30 is an
      independent risk factor for lymphedema, whereas a BMI of 25- <30 is not. Large
      post-operative weight fluctuations also increase risk of lymphedema. Patients
      with a pre-operative BMI >= 30 and those who experience large weight fluctuations
      during and after treatment for breast cancer should be considered at higher-risk
      for lymphedema. Close monitoring or early intervention to ensure optimal
      treatment of the condition may be appropriate for these patients.

PMID- 24122391
TI  - Distinct nuclear receptor expression in stroma adjacent to breast tumors.
AB  - The interaction between breast tumor epithelial and stromal cells is vital for
      initial and recurrent tumor growth. While breast cancer-associated stromal cells
      provide a favorable environment for proliferation and metastasis, the molecular
      mechanisms contributing to this process are not fully understood. Nuclear
      receptors (NRs) are intracellular transcription factors that directly regulate
      gene expression. Little is known about the status of NRs in cancer-associated
      stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene
      expression profiles of all 48 NR family members in a collection of primary
      cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor
      (ER)alpha positive breast cancers (n = 9) and normal breast adipose fibroblasts
      (NAFs) (n = 7). Thirty-three of 48 NRs were expressed in both the groups, while
      11 NRs were not detected in either. Three NRs (dosage-sensitive sex reversal,
      adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1); estrogen
      related receptor beta (ERR-beta); and RAR-related orphan receptor beta (ROR
      beta)) were only detected in NAFs, while one NR (liver receptor homolog-1 (LRH
      1)) was unique to CAFs. Of the NRs co-expressed, four were significantly down
      regulated in CAFs compared with NAFs (RAR-related orphan receptor-alpha (ROR
      alpha); Thyroid hormone receptor-beta (TR-beta); vitamin D receptor (VDR); and
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma)). Quantitative
      immunohistochemistry for LRH-1, TR-beta, and PPAR-gamma proteins in stromal
      fibroblasts from an independent panel of breast cancers (ER-positive (n = 15), ER
      negative (n = 15), normal (n = 14)) positively correlated with mRNA expression
      profiles. The differentially expressed NRs identified in tumor stroma are key
      mediators in aromatase regulation and subsequent estrogen production. Our
      findings reveal a distinct pattern of NR expression that therefore fits with a
      sustained and increased local estrogen microenvironment in ER-positive tumors.
      NRs in CAFs may provide a new avenue for the development of intratumoral-targeted
      therapies in breast cancer.

PMID- 24122392
TI  - Preemptive tumor profiling for biomarker-stratified early clinical drug
      development in metastatic breast cancer patients.
AB  - Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast
      cancer patients. The utility of agents modulating hormone receptors, synthesis of
      steroid hormones, or HER2-targeting agents has been greatly enhanced by the
      detection of predictive biomarkers in diagnostic tumor samples. Based on deeper
      understanding of breast cancer biology multiple drug candidates have been
      developed to modulate additional molecular targets which may associate with
      specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly
      incorporated in early clinical trials, thus demanding a new process of patient
      selection. Here, we describe the implementation of preemptive, multiplexed
      biomarker profiling linked to standard diagnostic algorithms for metastatic
      breast cancer patients treated at the West German Cancer Center. Profiling for
      experimental biomarkers was prospectively offered to patients with metastatic
      breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed,
      paraffin-embedded tumor samples were retrieved and studied for potentially
      "actionable" biomarkers related to active clinical trials by
      immunohistochemistry, amplicon sequencing, and in situ hybridization. The
      clinical course of those "profiled" patients was closely monitored to offer trial
      participation whenever applicable. Here, we report results from the first 131
      patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2
      %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected
      next to established biomarkers such as estrogen (67 %) and progesterone receptor
      expression (52 %), and HER2 overexpression or amplification (23 %). So far 16
      "profiled" patients (12 %) have been enrolled in biomarker-stratified early
      clinical trials. Preemptive profiling of investigational biomarkers can be
      integrated into the diagnostic algorithm of a large Comprehensive Cancer Center.
      Extensive administrative efforts are required to successfully enroll "profiled"
      patients with metastatic breast cancer in early clinical trials stratified by
      exploratory biomarkers.

PMID- 24122393
TI  - Reduction of tumor angiogenesis induced by desmopressin in a breast cancer model.
AB  - Desmopressin (DDAVP), a synthetic peptide analog of vasopressin, is a safe
      antidiuretic and hemostatic compound that acts as a selective agonist for the
      vasopressin V2 membrane receptor. It is known that DDAVP can inhibit progression
      of residual metastatic cells and also improves chemotherapy effects in
      preclinical breast cancer models. Here, we explored the effects of DDAVP on tumor
      angiogenesis using the aggressive F3II mammary carcinoma in syngeneic Balb/c
      mice. Intravenous administration of the compound (2 MUg/kg) markedly decreased
      vascularization of growing subcutaneous tumors, as well as inhibited the early
      angiogenic response around intradermal inoculation sites. In vitro studies
      confirmed the presence of vasopressin V2 receptors on F3II cells and a modest
      antiproliferative activity of DDAVP. Interestingly, conditioned media from F3II
      monolayers exposed to low doses of DDAVP (100 nM) significantly increased
      angiostatin formation in the presence of purified plasminogen. Such increase was
      associated with an enhancement of tumor-secreted urokinase-type plasminogen
      activator, suggesting the proteolytic conversion of plasminogen to angiostatin in
      vitro. Similar results were observed with the MCF-7 human breast carcinoma, a
      cell line known to express the vasopressin V2 receptor. No direct effects of
      DDAVP (100 nM-1 MUM) were found on capillary-like tube formation by human
      microvascular cells HMVEC. Our studies showed that DDAVP induces anti-angiogenic
      effects that may be associated with the generation of angiostatin by tumor cells.
      Further preclinical studies with DDAVP and other vasopressin analogs are
      warranted to determine their potential in cancer management.

PMID- 24122394
TI  - GH52 xylosidase from Geobacillus stearothermophilus: characterization and
      introduction of xylanase activity by site-directed mutagenesis of Tyr509.
AB  - A xylosidase gene, gsxyn, was cloned from the deep-sea thermophilic Geobacillus
      stearothermophilus, which consisted of 2,118 bp and encoded a protein of 705
      amino acids with a calculated molecular mass of 79.8 kDa. The GSxyn of glycoside
      hydrolase family 52 (GH52) displayed its maximum activity at 70  degrees C and pH
      5.5. The K m and k cat values of GSxyn for rhoNPX were 0.48 mM and 36.64 s-1,
      respectively. Interestingly, a new exo-xylanase activity was introduced into
      GSxyn by mutating the tyrosine509 into glutamic acid, whereas the resultant
      enzyme variant, Y509E, retained the xylosidase activity. The optimum xylanase
      activity of theY509E mutant displayed at pH 6.5 and 50  degrees C, and retained
      approximately 45 % of its maximal activity at 55  degrees C, pH 6.5 for 60 min.
      The K m and k cat values of the xylanase activity of Y509E mutant for beechwood
      xylan were 5.10 mg/ml and 22.53 s-1, respectively. The optimum xylosidase
      activity of theY509E mutant displayed at pH 5.5 and 60  degrees C. The K m and k
      cat values of the xylosidase activity of Y509E mutant for rhoNPX were 0.51 mM and
      22.53 s-1, respectively. This report demonstrated that GH52 xylosidase has
      provided a platform for generating bifunctional enzymes for industrially
      significant and complex substrates, such as plant cell wall.

PMID- 24122395
TI  - Youth-adult partnership: exploring contributions to empowerment, agency and
      community connections in Malaysian youth programs.
AB  - Youth-adult partnership (Y-AP) has emerged as a key practice for enacting two
      features of effective developmental settings: supportive adult relationships and
      support for efficacy and mattering. Previous studies have shown that when youth,
      supported by adults, actively participate in organizational and community
      decision making they are likely to show greater confidence and agency,
      empowerment and critical consciousness, and community connections. Most of the
      extant research on Y-AP is limited to qualitative studies and the identification
      of organizational best practices. Almost all research focuses on Western
      sociocultural settings. To address these gaps, 299 youth, age 15 to 24, were
      sampled from established afterschool and community programs in Malaysia to
      explore the contribution of Y-AP (operationalized as having two components: youth
      voice in decision-making and supportive adult relationships) to empowerment,
      agency and community connections. As hypothesized, hierarchical regressions
      indicated that program quality (Y-AP, safe environment and program engagement)
      contributed to agency, empowerment and community connections beyond the
      contribution of family, school and religion. Additionally, the Y-AP measures
      contributed substantially more variance than the other measures of program
      quality on each outcome. Interaction effects indicated differences by age for
      empowerment and agency but not for community connections. The primary findings in
      this inquiry replicate those found in previous interview and observational
      oriented studies. The data suggests fertile ground for future research while
      demonstrating that Y-AP may be an effective practice for positive youth
      development outside of Western settings.

PMID- 24122396
TI  - Thermal denaturation and aggregation of apoform of glycogen phosphorylase b.
      Effect of crowding agents and chaperones.
AB  - The effect of protein and chemical chaperones and crowders on thermal stability
      and aggregation of apoform of rabbit muscle glycogen phosphorylase b (apoPhb) has
      been studied at 37 degrees C. Proline suppressed heat-induced loss in ability of
      apoPhb to reconstitution at 37 degrees C, whereas alpha-crystallin did not reveal
      a protective action. To compare the antiaggregation activity of intact and
      crosslinked alpha-crystallins, an adsorption capacity (AC) of a protein chaperone
      with respect to a target protein was estimated. This parameter is a measure of
      the antiaggregation activity. Crosslinking of alpha-crystallin results in 11-fold
      decrease in the initial AC. The nonlinear character of the relative initial rate
      of apoPhb aggregation versus the [intact alpha-crystallin]/[apoPhb] ratio plot is
      indicative of the decrease in the AC of alpha-crystallin with increasing the
      [alpha-crystallin]/[apoPhb] ratio and can be interpreted as an evidence for
      dynamic chaperone structure and polydispersity of alpha-crystallin-target protein
      complexes. As for chemical chaperones, a semisaturation concentration of the
      latter was used as a characteristic of the antiaggregation activity. A decrease
      in the semisaturation concentration for proline was observed in the presence of
      the crowders (polyethylene glycol and Ficoll-70).

PMID- 24122397
TI  - Evolutionary distributions and competition by way of reaction-diffusion and by
      way of convolution.
AB  - Evolution by natural selection is the most ubiquitous and well understood process
      of evolution. We say distribution instead of the distribution of the density of
      populations of phenotypes across the values of their adaptive traits. A phenotype
      refers to an organism that exhibits a set of values of adaptive traits. An
      adaptive trait is a trait that a phenotype exhibits where the trait is subject to
      natural selection. Natural selection is a process by which populations of
      different phenotypes decline at different rates. An evolutionary distribution
      (ED) encapsulates the dynamics of evolution by natural selection. The main
      results are: (i) ED are derived by way of PDE of reaction-diffusion type and by
      way of integro-differential equations. The latter capture mutations through
      convolution of a kernel with the rate of growth of a population. The kernel
      controls the size and rate of mutations. (ii) The numerical solution of a
      logistic-like ED driven by competition corresponds to a bounded traveling wave
      solution of population models based on the logistic. (iii) Competition leads to
      increase in diversity of phenotypes on a single ED. Diversity refers to change in
      the number of local maxima (minima) within the bounds of values of adaptive
      traits. (iv) The principle of competitive exclusion in the context of evolution
      depends, smoothly, on the size and rate of mutations. (v) We identify the
      sensitivity-with respect to survival-of phenotypes to changes in values of
      adaptive traits to be an important parameter: increase in the value of this
      parameter results in decrease in evolutionary-based diversity. (vi) Stable ED
      corresponds to Evolutionary Stable Strategy; the latter refers to the outcome of
      a game of evolution.

PMID- 24122398
TI  - A realistic host-vector transmission model for describing malaria prevalence
      pattern.
AB  - Malaria continues to be a major public health concern all over the world even
      after effective control policies have been employed, and considerable
      understanding of the disease biology have been attained, from both the
      experimental and modelling perspective. Interactions between different general
      and local processes, such as dependence on age and immunity of the human host,
      variations of temperature and rainfall in tropical and sub-tropical areas, and
      continued presence of asymptomatic infections, regulate the host-vector
      interactions, and are responsible for the continuing disease prevalence
      pattern.In this paper, a general mathematical model of malaria transmission is
      developed considering short and long-term age-dependent immunity of human host
      and its interaction with pathogen-infected mosquito vector. The model is studied
      analytically and numerically to understand the role of different parameters
      related to mosquitoes and humans. To validate the model with a disease prevalence
      pattern in a particular region, real epidemiological data from the north-eastern
      part of India was used, and the effect of seasonal variation in mosquito density
      was modelled based on local climactic data. The model developed based on general
      features of host-vector interactions, and modified simply incorporating local
      environmental factors with minimal changes, can successfully explain the disease
      transmission process in the region. This provides a general approach toward
      modelling malaria that can be adapted to control future outbreaks of malaria.

PMID- 24122399
TI  - Propensity score matched lesion-based comparison of long-term  clinical and
      angiographic outcomes after placement of sirolimus  (Cypher Bx Velocity) and
      paclitaxel (TAXUS Express)-eluting  stents for de novo native coronary stenosis.
AB  - Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx
      Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were
      firstly compared in Japan. During PES-available period from May 2007 to February
      2009, 1068 nonrandomized consecutive de novo native coronary lesions treated
      either with a PES (682 lesions) or SES were enrolled in this study, and a
      retrospective examination was conducted in April 2013. During that interval, the
      use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the
      baselines with a propensity score matching analysis produced 383 lesions in each
      arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal
      recurrent myocardial infarction, and definite stent thrombosis) after placement
      of SES (2.1 %; mean follow-up, 1400 +/- 290 days) was not significantly different
      from that in the PES group (2.6 %; 1394 +/- 325 days, p = 0.637). SES did not
      relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p =
      0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in
      each arm), the incidence of binary restenosis (percent diameter stenosis [%DS]
      >50 %) in the SES group (12.0 %; mean follow-up, 477 +/- 281 days) was not
      significantly different from that in the PES group (14.5 %; 497 +/- 341 days, p =
      0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40
      1.32; p = 0.295). In conclusion, the present propensity score matched lesion
      based analysis firstly showed the statistical equivalent long-term clinical and
      angiographic outcomes after either SES or PES placement for de novo native
      coronary lesion in Japanese patients in a daily practice environment.

PMID- 24122400
TI  - Influence of nanohydroxyapatite surface properties on Staphylococcus epidermidis
      biofilm formation.
AB  - Nanohydroxyapatite (nanoHA), due to its chemical properties, has appeared as an
      exceptionally promising bioceramic to be used as bone regeneration material.
      Staphylococcus epidermidis have emerged as major nosocomial pathogens associated
      with infections of implanted medical devices. In this work, the purpose was to
      study the influence of the nanoHA surface characteristics on S. epidermidis RP62A
      biofilm formation. Therefore, two different initial inoculum concentrations (Ci)
      were used in order to check if these would affect the biofilm formed on the
      nanoHA surfaces. Biofilm formation was followed by the enumeration of cultivable
      cells and by scanning electron microscopy. Surface topography, contact angle,
      total surface area and porosimetry of the biomaterials were studied and
      correlated with the biofilm data. The surface of nanoHA sintered at 830
      (nanoHA830) showed to be more resistant to S. epidermidis attachment and
      accumulation than that of nanoHA sintered at 1000 (nanoHA1000). The biofilm
      formed on nanoHA830 presented differences in terms of structure, surface coverage
      and EPS production when compared to the one formed on nanoHA1000 surface. It was
      observed that topography and surface area of nanoHA surfaces had influence on the
      bacterial attachment and accumulation. Ci influenced bacteria attachment and
      accumulation on nanoHA surfaces over time. The choice of the initial inoculum
      concentration was relevant proving to have an effect on the extent of adherence
      thus being a critical point for human health if these materials are used in
      implantable devices. This study showed that the initial inoculum concentration
      and surface material properties determine the rate of microbial attachment to
      substrata and consequently are related to biofilm-associated infections in
      biomaterials. 

PMID- 24122401
TI  - Carbapenem-Resistant Enterobacteriaceae: Laboratory Detection and Infection
      Control Practices.
AB  - Over the past decade, carbapenem-resistant Enterobacteriaceae (CRE) have become
      one of the most challenging problems in infectious diseases. Fast and accurate
      detection of carbapenem resistance is crucial for guiding the treatment of the
      individual patient as well as for instituting proper infection control measures
      to limit the spread of the organism. Currently there are no consensus
      recommendations for screening, detection and confirmation of CRE either on the
      clinical or the laboratory side. In infection control, data from controlled
      intervention studies is largely missing and most recommendations have been
      deduced from outbreak situations. From the available limited evidence, infection
      control guidelines have been developed in most countries at national, regional
      and hospital levels. The aim of this review is to summarize the currently
      available laboratory methods and infection control options.

PMID- 24122403
TI  - Effect of general symptom level, specific adverse events, treatment patterns, and
      patient characteristics on health-related quality of life in patients with
      multiple myeloma: results of a European, multicenter cohort study.
AB  - PURPOSE: Novel multiple myeloma (MM) therapies have increased patient longevity
      but are often associated with notable symptom burden. This study quantified the
      effect of general symptom level, specific symptoms, and treatment-related adverse
      events (AEs) on MM patients' health-related quality of life (HRQoL). METHODS: The
      European Organization for Research and Treatment of Cancer (EORTC) generic cancer
      questionnaire (Quality of Life Questionnaire Core 30) and MM-specific
      questionnaire (QLQ-MY20) were used in this study to assess patients' HRQoL. Data
      were collected on sociodemographics, disease and treatment history, and the
      presence/severity of MM-related symptoms or treatment-related AEs from patients
      with MM in UK and German centers. Multiple regression analyses were conducted.
      RESULTS: Of 154 patients (63 % male; mean age, 66.4 years; mean time since
      diagnosis, 3.7 years; 52 % currently on treatment; and 43 % with >= 1 prior MM
      therapy), 25, 32, 31, and 11 % were severely symptomatic, moderately symptomatic,
      mildly symptomatic, and asymptomatic, respectively. Fatigue (59 %), bone pain (51
      %), sleepiness (36 %), hypoesthesia or paresthesia (33 %), and muscle cramps (31
      %) were most commonly reported. Moderate and severe general symptom levels, bone
      symptoms, depression, and mental status changes were identified as strong
      determinants of HRQoL. CONCLUSIONS: Severity, type of disease symptoms, and
      treatment related AEs are important HRQoL determinants in patients with MM,
      allowing for targeted treatment.

PMID- 24122404
TI  - A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in
      patients with colorectal cancer.
AB  - BACKGROUND: Prolonged neurotoxicity after systemic chemotherapy has the potential
      to impact on quality of life. We explored the frequency of persistent peripheral
      neuropathy in patients who received oxaliplatin for colorectal cancer at two
      local centres. PATIENTS AND METHODS: Questionnaires were sent to patients who
      completed treatment with oxaliplatin for colorectal cancer at least 20 months
      prior to entering the study. Neuropathy questions were adapted from the FACT/GOG
      Ntx (V.4) questionnaire. RESULTS: Of the 56 eligible patients, 27 returned the
      questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms
      during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time
      of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9-79.4 %) were
      still symptomatic with 12 patients (44.4 %; 95%CI 26.8-63.3) having grade-2 or
      grade-3 symptoms and three patients (11.1 %; 95%CI 2.9-27.3) having grade-3
      neuropathic symptoms. Participants who received more than 900 mg/m2 oxaliplatin
      had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p =
      0.031, RR = 8.3 95%CI = 1.2-57.4). There was a trend toward increased risk of
      persistent neuropathy of any grade among participants with a history of regular
      alcohol use (p = 0.051; RR = 1.7 95%CI 1.0-2.8). CONCLUSION: Persistent
      oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and
      the rate of grade-2 and grade-3 symptoms could be considerably higher than
      previous reports.

PMID- 24122405
TI  - Orphan symptoms in advanced cancer patients followed at home.
AB  - Orphan symptoms are rarely assessed, particularly at home. The aim of this
      multicenter prospective study was to assess the prevalence of these symptoms and
      eventual factors possibly associated in advanced cancer patients at admission of
      a home care program. A prospective study was performed at three home care
      programs in Italy. Patients' data were collected, including age, sex, diagnosis,
      and Karnofsky status. Possible contributing factors were analyzed; preexisting
      neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of
      dehydration clinically evident and/or oliguria, possible biochemical parameters
      when available, data regarding recent chemotherapy, opioids and doses, use of
      neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti
      inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating,
      pruritus, and tenesmus, either rectal or vesical, were assessed, according to a
      preliminary definition, at time of home care program admission. Three hundred
      sixty-two patients were surveyed at the three home care programs. Globally, 48
      patients presented one or more orphan symptoms in the period taken into
      consideration, and 7 patients presented more than 1 symptom. One patient
      presented occasional and diffuse myoclonus. Nineteen patients presented sweating,
      13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine
      patients presented rectal or vesical tenesmus. There was a significant
      correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P =
      0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not
      associated to any factor. Hiccup was associated with gender (males, P = 0.006)
      and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019)
      and sweating (P = 0.028). Although the symptoms examined have a low prevalence in
      advanced cancer patients admitted to home care, the distress for patients may be
      high and deserve further analyses. Given the low prevalence of these symptoms,
      large studies are needed to find possible associated factors. 

PMID- 24122406
TI  - Information needs and Internet use in urological and breast cancer patients.
AB  - AIMS: This study aims to describe the information needs of urological and breast
      cancer patients and factors related to use of the Internet as a source of health
      information. METHODOLOGY: A cross-sectional descriptive study was carried out,
      using individual questionnaire-based interviews held during the oncology
      appointments of 169 patients with urological cancer and 100 with breast cancer at
      the Virgen de las Nieves University Hospital in Granada, Spain. The variables
      studied were use of the Internet as a source of health information, health
      status, patient's role in the decision-making process, information sources,
      satisfaction with the health-care system, type of information received, and
      Internet use. A multivariate logistic regression analysis was carried out.
      RESULTS: Breast cancer patients are more concerned with long-term results and the
      effects on their family and personal life. They are also interested in the
      experiences of other patients and support groups or staff who could help them to
      cope with their illness. The information needs of patients with urological cancer
      are linked to short-term alternative treatments, their sex life, keeping healthy,
      and exercise. More clinical aspects, such as tests and experiments linked to
      their treatment, are not a frequent information need. The factors linked to use
      of the Internet as a source of health information are younger age, high level of
      education, the patient's active role in the decision-making process, and
      undergoing more aggressive treatment. There is no link between using the Internet
      as a source of health information and level of satisfaction with the health-care
      system, or with Internet use in general. CONCLUSION: Patients need additional
      information about their illness on top of that given to them by health-care
      staff, and they often use the Internet to find it. The greatest information need
      is related to the effects of their illness on their day-to-day life. Health-care
      staff should provide patients with advice about reliable websites and how to
      search the Internet.

PMID- 24122407
TI  - Assessing patient adherence to a complementary medicine treatment regimen in an
      integrative supportive care setting.
AB  - INTRODUCTION: Patients with cancer are frequently turning to complementary
      medicine (CM), often with the goal of improving quality of life outcomes. The
      purpose of the present study was to assess the adherence of patients referred by
      oncology practitioners to a CM consultation and treatment program. PATIENTS AND
      METHODS: A prospective registry protocol-based, preference study was conducted at
      a conventional oncology department. Patients undergoing chemotherapy were
      referred by participating oncology practitioners to a CM-trained integrative
      physician (IP) for consultation. Adherence to the integrative care (AIC) program
      was defined as attendance by patients at >=4 CM treatment sessions, with an
      interval of no more than 30 days between each session. RESULTS: A total of 282
      patients were referred by the study health-care professionals (HCPs), of whom 243
      (85.8%) were eventually seen by the study IP. Of these, 160 were found to be
      adherent to the treatment plan (AIC group), and 83 were nonadherent (non-AIC
      group). No significant differences were found between the two groups with respect
      to demographic characteristics, medical history, site of malignancy and/or
      recurrence, chemotherapy regimen, or severity of symptoms at baseline. The AIC
      group reported significantly greater rates of CM use for noncancer-related
      indications than the non-AIC group (EXP(B)=2.174, 95% confidence interval
      (C.I.)=1.1-4.295, p =0.025). Patients in the non-AIC group were referred more
      frequently by their HCP for gastrointestinal concerns than those in the AIC group
      (p =0.022). CONCLUSIONS: Previous use of CM for noncancer-related outcomes was
      found to be predictive of patient adherence to a CM treatment regimen provided
      within conventional oncology service.

PMID- 24122408
TI  - The internal and external validity of sluggish cognitive tempo and its relation
      with DSM-IV ADHD.
AB  - Studies of subtypes of DSM-IV attention-deficit/hyperactivity disorder (ADHD)
      have provided inconsistent support for the discriminant validity of the combined
      type (ADHD-C) and predominantly inattentive type (ADHD-I). A large sample of
      children and adolescents with ADHD (N = 410) and a comparison group without ADHD
      (N = 311) were used to test the internal and external validity of sluggish
      cognitive tempo (SCT), a dimension characterized by low energy and sleepy and
      sluggish behavior. SCT scores were then incorporated in analyses of ADHD subtypes
      to test whether the discriminant validity of ADHD-C and ADHD-I could be improved
      by including SCT symptoms as part of the criteria for ADHD-I. Factor analyses of
      parent and teacher ratings indicated that six SCT items loaded on a factor
      separate from symptoms of ADHD and other psychopathology, providing important
      support for the internal validity of SCT. The external validity of SCT was
      supported by significant associations between SCT and measures of functional
      impairment and neuropsychological functioning when symptoms of ADHD and other
      psychopathology were controlled. However, contrary to initial predictions, high
      levels of SCT did not identify a subgroup of ADHD-I that was clearly distinct
      from ADHD-C. Instead, the current results suggest that DSM-IV inattention and SCT
      are separate but correlated symptom dimensions that are each independently
      associated with important aspects of functional impairment and neuropsychological
      functioning.

PMID- 24122409
TI  - Probing the electronic structures and properties of neutral and charged arsenic
      sulfides (AsnS(-1,0,+1), n =1-7) using Gaussian-3 theory.
AB  - The structures and energies of neutral and charged arsenic sulfides As(n)S(
      1,0,+1) (n =1-7) were systematically investigated using the G3 method. The
      bonding properties and the stabilities of As(n)S and their ions were discussed.
      The adiabatic electron affinities (AEAs) and adiabatic ionization potentials
      (AIPs) were presented. The ground-state structures of As(n)S can be considered as
      the lowest-energy structure of neutral As(n+1) by replacing an As atom with a S
      atom, that is, "substitutional structure", in which the feature of sulfur bonding
      is edge-bridging. The ground-state structures of As(n)S+ tend to be derived from
      the lowest-energy structure of cation As(n)+ by attaching to a S atom, that is,
      "attaching structure", in which the sulfur can be three-fold coordinated. There
      is no rule to be found for the ground-state structure of anion As(n)S-, in which
      the sulfur can be a terminal atom. There are odd-even alternations in both AEAs
      and AIPs as a function of size of As(n)S. The dissociation energies of S, S-,
      and/or S+ from neutral As(n)S and their ions were calculated to examine their
      stabilities.

PMID- 24122410
TI  - Insight into the molecular mechanism about lowered  dihydrofolate binding
      affinity to dihydrofolate reductase-like 1  (DHFRL1).
AB  - Human dihydrofolate reductase-like 1 (DHFRL1) has been identified as a second
      human dihydrofolate reductase (DHFR) enzyme. Although DHFRL1 have high sequence
      homology with human DHFR, dihydrofolate (DHF) exhibits a lowered binding affinity
      to DHFRL1 and the corresponding molecular mechanism is still unknown. To address
      this question, we studied the binding of DHF to DHFRL1 and DHFR by using
      molecular dynamics simulation. Moreover, to investigate the role the 24th residue
      of DHFR/DHFRL1 plays in DHF binding, R24W DHFRL1 mutant was also studied. The van
      der Waals interaction are more crucial for the total DHF binding energies, while
      the difference between the DHF binding energies of human DHFR and DHFRL1 can be
      attributed to the electrostatic interaction and the polar desolvation free
      energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed
      to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of
      DHFRL1 with DHF as being affected by Arg24. The side chain of Arg24 in DHFRL1 can
      extend deeply into the binding sites of DHF and NADPH, and disturb the DHF
      binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1
      mutant. Additionally, the conformation of loop I in DHFRL1 was also studied in
      this work. Interestingly, the loop conformation resemble to normal closed state
      of Escherichia coli DHFR other than the closed state of human DHFR. We hope this
      work will be useful to understand the general characteristics of DHFRL1.

PMID- 24122411
TI  - Analogue study of peer influence on risk-taking behavior in older adolescents.
AB  - This experimental study aimed to examine whether adolescents act in a riskier
      manner in the presence of peers and whether peer presence alone influences risk
      behavior or if a direct influence process is necessary. Utilizing a behavioral
      task assessing risk-taking, 183 older adolescents (18-20 year olds) came to the
      laboratory alone once and then were randomized to one of three conditions as
      follows: alone, peers present, and peers encouraging. An interaction was found
      such that at baseline, there were no significant differences between the three
      conditions, but at the experimental session, there was a significant increase in
      risk task scores particularly for the encouraging condition. These findings
      challenge proposed models of the interaction between peer influence and risk
      taking by providing evidence that adolescents take more risks when being
      encouraged by peers, but that the presence of peers on its own does not lead to
      more risks than when completing the task alone.

PMID- 24122412
TI  - COUP-TFII in pancreatic adenocarcinoma: clinical implication for patient survival
      and tumor progression.
AB  - Despite the accumulating knowledge of alterations in pancreatic cancer molecular
      pathways, no substantial improvements in the clinical prognosis have been made
      and this malignancy continues to be a leading cause of cancer death in the
      Western World. The orphan nuclear receptor COUP-TFII is a regulator of a wide
      range of biological processes and it may exert a pro-oncogenic role in cancer
      cells; interestingly, indirect evidences suggest that the receptor could be
      involved in pancreatic cancer. The aim of this study was to evaluate the
      expression of COUP-TFII in human pancreatic tumors and to unveil its role in the
      regulation of pancreatic tumor growth. We evaluated COUP-TFII expression by
      immunohistochemistry on primary samples. We analyzed the effect of the nuclear
      receptor silencing in human pancreatic cancer cells by means of shRNA expressing
      cell lines. We finally confirmed the in vitro results by in vivo experiments on
      nude mice. COUP-TFII is expressed in 69% of tested primary samples and correlates
      with the N1 and M1 status and clinical stage; Kaplan-Meier and Cox regression
      analysis show that it may be an independent prognostic factor of worst outcome.
      In vitro silencing of COUP-TFII reduces the cell growth and invasiveness and it
      strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF-C.
      In nude mice, COUP-TFII silencing reduces tumor growth by 40%. Our results
      suggest that COUP-TFII might be an important regulator of the behavior of
      pancreatic adenocarcinoma, thus representing a possible new target for pancreatic
      cancer therapy. 

PMID- 24122413
TI  - Predicting life expectancy in patients with metastatic cancer receiving
      palliative radiotherapy: the TEACHH model.
AB  - BACKGROUND: Predicting life expectancy (LE) in patients with metastatic cancer
      who are receiving palliative therapies is a difficult task. The purpose of the
      current study was to develop a LE prediction model among patients receiving
      palliative radiotherapy (RT) that identifies those patients with short (< 3
      months) and long (> 1 year) LEs. METHODS: The records of 862 patients with
      metastatic cancer receiving palliative RT at the Dana-Farber/Brigham and Women's
      Cancer Center between June 2008 and July 2011 were retrospectively reviewed. Cox
      proportional hazards models were used to evaluate established and potential
      clinical predictors of LE to construct a model predicting LE of < 3 months and >
      1 year. RESULTS: The median survival was 5.6 months. On multivariate analysis,
      factors found to be significantly associated with a shorter LE were cancer type
      (lung and other vs breast and prostate), older age (> 60 years vs <= 60 years),
      liver metastases, Eastern Cooperative Oncology Group performance status (2-4 vs 0
      1), hospitalizations within 3 months before palliative RT (0 vs >= 1), and prior
      palliative chemotherapy courses (>= 2 vs 0-1). Patients were divided into 3
      groups with distinct median survivals: group A (those with 0-1 risk factors),
      19.9 months (95% confidence interval [95% CI, 13.9 months-31.1 months]); group B
      (those with 2-4 risk factors), 5.0 months (95% CI, 4.3 months -5.6 months); and
      group C (those with 5-6 risk factors), 1.7 months (95% CI, 1.2 months-2.1
      months). CONCLUSIONS: The TEACHH model (type of cancer, Eastern Cooperative
      Oncology Group performance status, age, prior palliative chemotherapy, prior
      hospitalizations, and hepatic metastases) divides patients receiving palliative
      RT into 3 distinct LE groups at clinically informative extremes of the LE
      spectrum. It holds promise to assist radiation oncologists in tailoring
      palliative therapies to a patient's LE.

PMID- 24122414
TI  - A biologically based model for recognition of 2-D occluded patterns.
AB  - In this work, we present a biologically inspired model for recognition of
      occluded patterns. The general architecture of the model is based on the two
      visual information processing pathways of the human visual system, i.e. the
      ventral and the dorsal pathways. The proposed hierarchically structured model
      consists of three parallel processing channels. The main channel learns invariant
      representations of the input patterns and is responsible for pattern recognition
      task. But, it is limited to process one pattern at a time. The direct channel
      represents the biologically based direct connection from the lower to the higher
      processing level in the human visual cortex. It computes rapid top-down pattern
      specific cues to modulate processing in the other two channels. The spatial
      channel mimics the dorsal pathway of the visual cortex. It generates a combined
      saliency map of the input patterns and, later, segments the part of the map
      representing the occluded pattern. This segmentation process is based on our
      hypothesis that the dorsal pathway, in addition to encoding spatial properties,
      encodes the shape representations of the patterns as well. The lateral
      interaction between the main and the spatial channels at appropriate processing
      levels and top-down, pattern-specific modulation of the these two channels by the
      direct channel strengthen the locations and features representing the occluded
      pattern. Consequently, occluded patterns become focus of attention in the ventral
      channel and also the pattern selected for further processing along this channel
      for final recognition.

PMID- 24122415
TI  - The effect of text continuity on spatial representation: route versus survey
      perspective.
AB  - Previous research has shown that people need spatial-sequential ability to
      process route information. In the current study, we focused not on the
      participant's ability but on the process of how spatial information is presented.
      We examined the hypothesis that constructing an accurate spatial representation
      from route descriptions requires text continuity more than from survey
      perspective. Forty-eight participants read a descriptive spatial text and then
      drew a map representing the text. We manipulated text continuity by transposing
      sentences in the spatial text and set three conditions: continuous, semi
      continuous, and discontinuous. The results showed that when a route perspective
      is used, learning performance decreases in the absence of text continuity (e.g.,
      in the semi-continuous and discontinuous conditions). This decrease in
      performance was modest when participants used a survey perspective. These results
      indicate that there is a tendency to rely on sequentially presented information
      when using the route perspective, not only at the surface level of description,
      but also at the level of cognitive processing.

PMID- 24122416
TI  - Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of
      animal models.
AB  - The development of suitable animal models is essential to experimental research
      on intraperitoneal chemotherapy (IPC). This review of the English literature
      (MEDLINE) presents a detailed analysis of current animal models and gives
      recommendations for future experimental research. Special consideration should be
      given to cytotoxic drug dose and concentration, tumor models, and outcome
      parameters.

PMID- 24122417
TI  - Increased expression of microRNA-9 predicts an unfavorable prognosis in human
      glioma.
AB  - microRNA-9 (miR-9) has been found to be upregulated along with tumor progression
      of gliomas by microarray-based expression profiling, and also be strongly linked
      to glioblastoma subtypes. However, its prognostic value in glioma is still
      elusive. miR-9 expression in human gliomas and nonneoplastic brain tissues was
      measured by real-time quantitative RT-PCR assay. miR-9 expression in glioma
      tissues was significantly higher than that in corresponding nonneoplastic brain
      tissues (P?0.001). The increased expression of miR-9 was more frequently observed
      in glioma tissues with high WHO grade than those with low WHO grade tissues (P =
      0.001). The expression levels of miR-9 in glioma tissues with low Karnofsky
      performance score (KPS) were also significantly higher than those with high KPS
      (P = 0.008). Moreover, the overall survival of glioma patients with high miR-9
      expression was obviously lower than that with low miR-9 expression (P?0.001).
      Multivariate analysis further showed that high miR-9 expression was an
      independent prognostic factor for overall survival in glioma patients (P = 0.01).
      More importantly, the subgroup analyses indicated that the overall survival of
      glioma patients with high WHO grade (III-IV) was significantly worse for high miR
      9 expression group than for low miR-9 expression group (P?0.001), but no
      significant difference was found for patients with low WHO grade (I-II). These
      findings suggest for the first time that the increased expression of miR-9 may
      play an important role in tumor progression in human gliomas. miR-9 might be a
      useful marker for predicting the clinical outcome of glioma patients, especially
      for advanced subtypes.

PMID- 24122418
TI  - Adipose stromal-vascular fraction-derived paracrine factors regulate
      adipogenesis.
AB  - Visceral and subcutaneous adipose tissue depots have distinct features and
      contribute differentially to metabolic disease. Therefore, the adipogenic
      potential of different fat depots was investigated and found to be higher in
      subcutaneous compared with visceral stromal-vascular fraction (SVF), which
      contains adipocyte precursor cells. This increased differentiation capacity was
      not due to elevated numbers of Lin-Sca1+CD29+CD34+Pref1+ precursor cells, as the
      number of preadipocytes was higher in visceral than in subcutaneous SVF. The
      secreted heat-sensitive factors from the SVF inhibited adipocyte differentiation
      more in visceral than in subcutaneous SVF. In order to explore secreted proteins
      that potentially inhibit differentiation, the secretome of murine SVF was
      analyzed by mass spectrometry, which resulted in the identification of 113
      secreted proteins with an overlap of 42 % between subcutaneous and visceral SVF.
      Comparison of the mRNA expression in SVF from both depots revealed 16 transcripts
      that were significantly expressed more in visceral than in subcutaneous SVF. A
      functional differentiation screen identified seven potential inhibitory
      candidates: biglycan, decorin, bone morphogenic protein 1, epidermal growth
      factor-containing fibulin-like extracellular matrix protein 2, elastin
      microfibril interfacer 1, matrix gla protein, and Sparc-like 1. For further
      verification, murine recombinant decorin or Sparc-like 1 was added to the media
      during the differentiation process leading to a dose-dependent decrease in
      adipogenesis. Further analysis will be necessary to assess the impact of the
      other candidates on adipocyte differentiation.

PMID- 24122419
TI  - Foxc2 over-expression in bone marrow mesenchymal stem cells stimulates osteogenic
      differentiation and inhibits adipogenic differentiation.
AB  - The forkhead box C2 (Foxc2) protein, a member of the forkhead/winged helix
      transcription factor family, is strongly expressed in developing embryo and is
      required in various developmental processes. However, the precise function of
      Foxc2 in osteoblast differentiation remains largely unknown. The present study
      investigated the role of Foxc2 overexpression on osteogenic and adipogenic
      differentiations. In our experiment, rabbit bone marrow mesenchymal stem cells
      (BMSCs) were transduced with lentiviral vectors containing Foxc2 or green
      fluorescent protein (GFP), and the gene expression and biological activity of
      Foxc2 were examined in vitro. The results showed that the mRNA and protein
      expressions of Foxc2 were stable and high in cells transduced with Foxc2 compared
      with those transduced with GFP. The overexpression of Foxc2 increased the mRNA
      and protein levels of COLI, OCN, and OPN; enhanced the activity of ALP after
      osteogenic induction; and decreased the expression of PPARgamma-2 and the total
      droplet number after adipogenic induction. In addition, Foxc2 enhanced the
      expression of beta-catenin, an important modulator of osteoblastogenesis. XAV939,
      a small molecule inhibitor of the Wnt-beta-catenin pathway, suppressed Foxc2
      mediated regulation of BMSC differentiation. These findings demonstrate that the
      overexpression of Foxc2 gene in BMSCs may promote osteogenic differentiation and
      inhibit adipogenic differentiation, and this effect can be mediated via
      activating the canonical Wnt-beta-catenin signaling pathway.

PMID- 24122420
TI  - Social impact of dialysis on children and their families.
AB  - OBJECTIVES: To evaluate the social consequences of dialysis on children and their
      parents. METHODS: From January through June 2012 short structured interviews with
      parents or caregivers of children on peritoneal dialysis (PD) or hemodialysis
      (HD) who were followed up at King Abdulaziz University Hospital, King Faisal
      Specialty Hospital and Research Center, or the Kidney Center at King Fahad
      Hospital were conducted. Data were analyzed using the Statistical Package for the
      Social Sciences. RESULTS: Thirty six children (20 boys and 16 girls [corrected] )
      and their families were included. The mean (SD) age of the children was 11.5+/
      6.87 y, and the mean (SD) duration of dialysis was 28+/-11.32 mo. Only one third
      of the families had the opportunity to choose the modality of dialysis. Both
      modalities of dialysis had a negative effect on fathers' jobs in over 50% of the
      cases. Similarly, both modalities of treatment had a considerable impact on the
      quality of care provided by the mothers to other family members. There was no
      difference between the two modalities on the frequency of admissions.
      CONCLUSIONS: Both PD and HD had a negative impact on fathers' jobs and on the
      level of care provided by mothers to the rest of the family.

PMID- 24122421
TI  - Cushing's disease developing independently from acute lymphoblastic leukemia.

PMID- 24122422
TI  - Epidemiological Features of Aplastic Anemia in Indian Children.
AB  - OBJECTIVES: To study the socio-demographic profile and clinico-hematological
      features of aplastic anemia in children presenting at a single institution over 5
      y. METHODS: Patients below the age of 15 y presenting with features of aplastic
      anemia were included in the study. Epidemiology, clinico-hematological features
      and treatment received were recorded in all the cases. Serology for hepatitis A,
      B, C, E, EBV, parvovirus and HIV was carried out. Cytogenetic studies were
      available in approximately half of the patients. RESULTS: One hundred eighty five
      patients were diagnosed with aplastic anemia. Ten patients with inherited bone
      marrow failure syndrome (IBMFS) were excluded. Median age was 8 y (range 4-14 y)
      with a male to female ratio of 2.4:1. Pallor (100 %) followed by bleeding
      manifestations (83.8 %) and fever (73.5 %) were most common presenting symptoms.
      One hundred twenty patients (70 %) were classified as severe, 36 (21 %) very
      severe and 17 (9 %) non-severe aplastic anemia. Viral markers for parvovirus,
      Epstein barr virus and hepatitis were positive in 25.8 %, 20 % and 6.7 % patients
      respectively. Six patients had history of varicella infection in recent past
      (within 6 mo). Very few patients (30) could afford immunosuppressive therapy
      (IST) and had suboptimal response (29.7 %). CONCLUSIONS: Majority of patients had
      idiopathic aplastic anemia. Very severe aplastic anemia and severe aplastic
      anemia were frequent. Few patients received IST and had suboptimal response.
      There is need to establish a national registry for aplastic anemia.

PMID- 24122423
TI  - Introduction: attachment theory and psychotherapy.
AB  - In this introduction to the JCLP: In Session 69(11) issue on attachment theory
      and psychotherapy, the key points of attachment theory (Bowlby, , , 1981) and its
      relevance to psychotherapy are briefly described. The aim of this issue is to
      provide case illustrations of how an attachment theory perspective and principles
      can expand our understanding of psychotherapy practice. 

PMID- 24122425
TI  - Integration and innovation: first issue of cardiovascular intervention and
      therapeutics.

PMID- 24122424
TI  - Hydrocarbon production in high density Botryococcus braunii race B continuous
      culture.
AB  - Continuous cultures of Botryococcus braunii race B were maintained at
      photosynthetic cell densities as high as 20 g dry weight per liter for up to 3
      months. Growth associated triterpene hydrocarbon accumulation was nearly constant
      at 22.5% of dry weight for a range of growth rates maintained by daily
      replacement of 5-15% of the respective cultures. The ability to achieve high cell
      concentrations and oil levels of roughly 5 g triterpene oil/L resulted from a
      combination of high light (~ 1/4 full sun for 15 h/day) and replenishing
      stoichiometrically balanced growth medium. Due to light-limited growth
      conditions, cell concentration dropped nearly linearly with increased dilution
      rate. This reduction in cell number resulted in increased productivity per cell
      at higher dilution rates and was accompanied by a dramatic increase in algae
      colony size from 0.09 to 0.343 mm at high dilution rate. This change in colony
      size resulted in an equally dramatic change in optical density (OD) per gram dry
      weight, which precluded use of simple correlations of OD and cell concentration.
      A trickle-film photobioreactor was also demonstrated as a scalable approach to
      achieving these ultra-high cell concentrations. Additional media analysis
      revealed a steady increase in photobioreactor conductivity suggesting an
      accumulation of ions may be the reason for rapid culture crash and washout
      observed at all dilution rates after several months of continuous operation. The
      volumetric productivity of 22.5 mg oil/L/photo-h reported here is more than an
      order of magnitude higher than previous reports for B. braunii race B, reflecting
      the high cell densities used in this work and substantiating a higher metabolic
      rate for B. braunii race B than previously surmised from its relatively long
      doubling times.

PMID- 24122426
TI  - Optical coherence tomography imaging: current status and future perspectives :
      Current and future developments in OCT.
AB  - Optical coherence tomography (OCT) is an optical analogue of intravascular
      ultrasound that provides high-resolution (10-20 MUm) cross-sectional images of
      coronary arteries. The micron-scale resolution of OCT has an ability to capture
      in vivo what was previously seen only through a pathologist's microscope. OCT can
      differentiate three types of atherosclerotic plaque components (fibrous,
      fibrocalcific and lipid-rich) with high sensitivity and specificity. Early in
      vitro and in vivo studies have demonstrated a possibility of OCT for identifying
      vulnerable plaque features, in particular the quantification of plaque rupture,
      intracoronary thrombus, thin-capped fibroatheroma and the distribution of
      macrophages within the fibrous cap. In addition, OCT has shown its effectiveness
      in imaging the short-term and long-term results of percutaneous coronary
      intervention. OCT can precisely assess stent strut malapposition, tissue
      protrusion, coronary artery dissection, and neointimal hyperplasia following
      stent implantation. Recently, next-generation OCT, called Fourier-domain OCT, has
      already been shown to be a powerful enabling technology for coronary imaging. The
      novel developments with high frame rate and fast pullback speed simplifies
      procedural requirements and will eventually eliminate limitations of current OCT
      systems such as need for proximal vessel balloon occlusion during image
      acquisition. This report details current and future developments in OCT imaging,
      which include exciting technological advancements that will consolidate the
      position of OCT as a key diagnostic tool to complement the armamentarium of the
      cardiologist well into the future. 

PMID- 24122427
TI  - Coronary artery revascularization before peripheral vascular surgery in patients
      with peripheral arterial disease.
AB  - The prevalence of coronary artery disease (CAD) in patients with peripheral
      arterial disease (PAD) approaches 50%. The incidence of perioperative cardiac
      complications is high in patients undergoing peripheral vascular surgery (PVS).
      However, the long-term efficacy of coronary artery revascularization in patients
      with PAD prior to PVS remains controversial. We retrospectively analyzed the long
      term outcomes of 114 patients who underwent elective PVS. Coronary angiography
      (CAG) was performed routinely in all patients prior to the surgery. Preoperative
      CAG revealed CAD in 52 patients and no CAD in 62 patients (No-CAD group). Of the
      52 patients with CAD, 15 patients with effort angina (more than CCS class 2),
      myocardial ischemia proven by pharmacological stress scintigraphy, and/or
      multivessel disease with impaired left ventricular systolic function underwent
      coronary revascularization (CAD-R group). The remaining 37 patients with CAD were
      treated medically (CAD-M group). The rates of postoperative events within 30 days
      were 26.7% in the CAD-R group, 10.8% in the CAD-M group, and 8.1% in the No-CAD
      group, respectively (P = 0.13), and the rates of long-term cardiovascular events
      were 33.3, 21.6, and 21.0%, respectively (P = 0.60). Therefore, the acute and
      long-term clinical outcomes in the CAD-R group were comparable with the other
      groups. In this study, the patients with CAD who showed inducible myocardial
      ischemia and/or multivessel disease with impaired left ventricular systolic
      function underwent coronary artery revascularization prior to the elective PVS.
      The patients who underwent coronary revascularization prior to the PVS exhibited
      comparable long-term outcomes compared with the patients who showed CAD but
      without inducible myocardial ischemia and with those without CAD. These data
      suggest that the evaluation of CAD and myocardial ischemia to determine the
      therapeutic strategy for CAD before elective PVS would be needed. 

PMID- 24122428
TI  - Low responsiveness to thienopyridine in hemodialysis patients.
AB  - We sought to evaluate whether thienopyridine low responsiveness, a predictor of
      stent thrombosis, is found in hemodialysis patients. We measured platelet
      aggregation at the site of implantation of drug-eluting stents in 333 patients
      with angina pectoris undergoing dual anti-platelet therapy. Thirty-one patients
      were on hemodialysis (HD group), and 302 were not (N-HD group). We used a novel
      whole-blood aggregometer. The aggregometer used the screen filtration method,
      with adenosine diphosphate as an agonist. The concentration of agonist required
      to induce 50% of the maximum pressure rate was calculated and indicated as the
      platelet aggregatory threshold index (PATI). Low responsiveness for
      thienopyridine was defined if the PATI levels were <4 MUmol/l. PATI levels
      (MUmol/l) were significantly lower in the HD group than in the N-HD group (6.8 +/
      4.8 vs. 9.1 +/- 5.4, P = 0.023), and the rate of low responsiveness for
      thienopyridine was significantly higher in the HD group than in the N-HD group
      (45.7 vs. 26.8%, P = 0.019). Non-fatal myocardial infarction and stent thrombosis
      occurred in three of the HD group and in nine of the N-HD group (P = 0.122). Late
      stent thrombosis occurred at a significantly higher rate in the HD group than in
      the N-HD group (P = 0.002). The rate of target lesion revascularization was
      significantly higher in the HD group than in the N-HD group (38 vs. 11.8%, P =
      0.0001). In conclusion, low responsiveness to thienopyridine, as an indicator of
      platelet reactivity, is found more frequently in hemodialysis patients. 

PMID- 24122429
TI  - Impact of catheter down-sizing and power injector use on the amount of contrast
      medium delivered.
AB  - The purpose of this study is to evaluate the effect of catheter down-sizing and
      power injector use on the amount of contrast medium delivered during diagnostic
      coronary angiography (CAG). We retrospectively studied 735 patients undergoing
      diagnostic CAG. Patients were divided into four groups according to catheter size
      [4 French (Fr) or 5 Fr] and the method of contrast injection (manual or power
      injection). Total contrast volume, procedure time, number of catheters used and
      angiogram quality were analyzed. Down-sizing catheters from 5 Fr to 4 Fr reduced
      the amount of contrast medium in both manual injection (from 153 +/- 22 to 137 +/
      17 ml, -10%, p < 0.0001) and power injection (from 135 +/- 12 to 125 +/- 16 ml, 
      7%, p < 0.0001). Introduction of power injection reduced the amount of contrast
      medium in both 4-Fr catheters (from 137 +/- 17 to 125 +/- 16 ml, -9%, p < 0.0001)
      and 5-Fr catheters (from 153 +/- 22 to 135 +/- 12 ml, -12%, p < 0.0001). A 28-ml
      (18%) reduction in contrast medium volume occurred when catheter down-sizing was
      combined with power injector use. Angiogram quality was not different among the
      four groups. Down-sizing the catheters from 5 Fr to 4 Fr and the use of a power
      injector reduced the amount of contrast medium delivered in CAG without reducing
      angiographic image quality. 

PMID- 24122430
TI  - Incidence and outcome of surgical procedures after sirolimus-eluting stent
      implantation: a report from the j-Cypher registry.
AB  - The incidence of surgical procedures after sirolimus-eluting stent (SES)
      implantation and, more importantly, the rate of perioperative stent thrombosis
      (ST) and/or other adverse events have not yet been adequately addressed. The
      incidence and outcome of the surgical procedures after SES implantation were
      prospectively evaluated in a large-scale multicenter registry of patients
      undergoing SES implantation. Among 12,824 patients enrolled in the registry,
      cumulative incidences of surgical procedures were 0.7% at 60 days, 5.1% at 1 year
      and 14.7% at 3 years. Surgical procedures were performed in 1,430 patients
      including non-coronary artery bypass graft (CABG) surgery in 1,275 patients and
      CABG in 189 patients. The incidences of death/myocardial infarction/ST (definite
      or probable) and ST (definite or probable) at 30 days after surgical procedures
      were 2.7 and 0.35%, respectively. Surgery performed within 60 days after SES
      implantation as compared with that performed beyond 60 days was associated with
      significantly higher incidences of death/myocardial infarction/ST (definite or
      probable) and ST (definite or probable) at 30 days after surgical procedures (6.4
      vs. 2.5%: P = 0.02 and 2.2 vs. 0.23%: P = 0.002, respectively). Surgery within 60
      days as well as hemodialysis and small body mass index were independent risk
      factors of death/myocardial infarction/ST (definite or probable) identified by
      multivariable analysis. Surgical procedures were required fairly often after SES
      implantation. The incidences of adverse cardiac events including ST after
      surgical procedures were acceptably low. Surgery within 60 days after SES
      implantation carried significantly higher risks as compared with those beyond 60
      days. 

PMID- 24122431
TI  - Gender differences in coronary plaque characteristics in patients with stable
      angina: a virtual histology intravascular ultrasound study.
AB  - The purpose of this study was to compare culprit coronary plaque characteristics
      between female and male patients with stable angina using virtual histology
      intravascular ultrasound (VH-IVUS). The target population consisted of three
      hundred and sixty-four consecutive patients with stable angina who underwent
      percutaneous coronary intervention (PCI) after VH-IVUS. The baseline
      characteristics and VH-IVUS results were compared between 72 female and 292 male
      patients. Culprit coronary plaque histological composition ratios, which were
      classified as fibrous (FI)%, fibro-fatty (FF)%, dense-calcium (DC)% and necrotic
      core (NC)%, were evaluated by VH-IVUS. The HbA1c (6.4 +/- 1.2% vs. 5.9 +/- 1.0%,
      p < 0.0001), total cholesterol (202 +/- 33 mg/dL vs. 189 +/- 34 mg/dL, p =
      0.004), and LDL-cholesterol (118 +/- 32 mg/dL vs. 110 +/- 27 mg/dL, p = 0.03)
      were higher in female patients compared to male patients. The FI ratio (55 +/-
      15% vs. 60 +/- 15%, p = 0.02) and FF ratio (9 +/- 8% vs. 12 +/- 10%, p = 0.02)
      were lower, but the DC ratio (12 +/- 13% vs. 9 +/- 11%, p = 0.01) and NC ratio
      (23 +/- 11% vs. 19 +/- 12%, p = 0.02) were higher in female patients than in male
      patients. The differences in coronary risk factors between females and males may
      be associated with coronary plaque characteristics. Differences in culprit
      coronary plaque composition were observed between female and male patients with
      stable angina. 

PMID- 24122432
TI  - Prevention of coronary slow flow/no reflow during percutaneous coronary
      intervention by the use of embolic protection device, 'Filtrap'.
AB  - A 68 year-old man underwent percutaneous coronary intervention (PCI). A 64 multi
      slice computed tomography (MSCT) demonstrated a non-calcified plaque with
      positive remodeling. Intravascular ultrasound showed severe attenuation which
      suggested high risk of coronary no reflow during PCI. In order to avoid this, we
      used an embolic protection device, Filtrap. Immediately after deployment of a
      Taxus stent, ST-elevation with chest pain and coronary no reflow appeared. After
      retrieval of the Filtrap device, ST-elevation and no reflow disappeared. The
      filter was filled with yellow materials. This case suggests two things: that 64
      MSCT can detect coronary plaque with high-risk of coronary no reflow during PCI;
      and that using a Filtrap device can effectively prevent the coronary no reflow
      during PCI. 

PMID- 24122433
TI  - A proposal for a quality system for herbal products.
AB  - Today, there is an increasing worldwide demand for botanicals. Developing
      countries heavily rely on plant-derived medicines for their primary healthcare.
      One reason amongst many is the relatively inexpensive process economics and the
      lack of stringent product governance associated with the exploitation of
      traditional plant medicines compared with modern medicine. Developed countries
      impose stringent good manufacturing practices and quality control measures on
      drug products derived from any manufacturing process, regardless of the primary
      raw material. However, several factors hamper the full-scale application of
      traditional plant medicines: lack of implementation of effective quality
      assurance in the manufacturing process; lack of traceability in the supply chain
      and associated value additions; and inefficient identification of molecular
      species that affect the therapeutic efficacy of the final product. There lacks an
      assessable, causative, and prognostic relationship between the raw materials, the
      manufacturing process and the final product quality. This article suggests some
      solutions that may be adopted by the phytodrug industry to widen its global reach
      and retain its credibility. Primarily among them is the implementation of hazards
      analysis and critical control point in the manufacturing process and employment
      of process analytical technology for ensuring minimal deviation from the
      manufacturing process of phytotherapeutics.

PMID- 24122434
TI  - Mechanical properties of revision ACL reconstruction.
AB  - The aim of this study is to evaluate the mechanical properties of a revision
      anterior cruciate ligament (ACL) reconstruction after redrilling the original
      tibial bone tunnel through a retained composite screw compared with initial soft
      tissue graft fixation. A total of 24 porcine tendons were fixed to porcine tibial
      tunnels with a 10 * 35 mm composite interference screw. Following the pullout
      test, a revision tunnel was drilled through the first interference screw and a
      second graft was fixed in the bone tunnel using a larger composite screw (11 * 35
      mm). Following insertion of the revision screw, the graft was reloaded as
      described for the primary reconstruction. Load versus displacement data were
      recorded for each test. There were no significant differences between the primary
      and revision reconstruction constructs for yield load (p = 0.62), linear
      stiffness (p = 0.18), maximum failure load (p = 0.57), and yield displacement (p
      = 0.46). These results indicate that the mechanical properties of tibial fixation
      for ACL reconstruction with a composite screw following a revision provide
      similar fixation compared with initial reconstruction in this model. Revising a
      failed composite ACL construct by means of overdrilling and reinstrumenting may
      provide fixation equivalent to the initial reconstruction.

PMID- 24122435
TI  - Biceps tenodesis versus allograft reconstruction for varus instability.
AB  - Although effective to restore stability in varus laxity, a fibula-based procedure
      such as figure-of-8 reconstruction can be technically demanding and requires use
      of allograft or autograft. Biceps rerouting offers an alternative without the
      potential complications of allograft or autograft procedures. It is not known
      whether biceps tenodesis is effective in addressing isolated varus laxity with
      lateral collateral ligament (LCL) rupture. We compared biceps tenodesis and
      figure-of-8 allograft reconstruction for restoration of varus stability. Nine
      knees were loaded at 10 N-m at 0- and 30-degree knee flexion in intact, LCL
      sectioned, and reconstructed state. Both biceps tenodesis and figure-of-8
      reconstruction restored varus stability to at least baseline stability.
      Normalized displacement with biceps tenodesis measured at time zero was
      significantly lower than with allograft reconstruction at 0 degrees (0.75 +/-
      0.26 vs. 1.09 +/- 0.31 degrees; p = 0.04) and 30 degrees (0.66 +/- 0.14 vs. 0.91
      +/- 0.27 degrees; p =  0.04). Biceps tenodesis was effective at restoring
      baseline varus stability in isolated varus laxity.

PMID- 24122436
TI  - Strain within the native and reconstructed MPFL during knee flexion.
AB  - There is little published data on the strain within the medial patellofemoral
      ligament (MPFL) and medial retinaculum through knee motion. This study was
      undertaken to evaluate the three-dimensional strain across the MPFL in the native
      state, using a proprietary visible-light stereophotogrammetry (VLS) system, and
      to compare the findings to the strain in a MPFL injury model and in two different
      reconstructed states. This is a controlled laboratory study. Eight cadaveric
      knees were marked along the MPFL and medial retinaculum, placed in an activity
      simulator, and taken through a range a motion. A proprietary VLS system was used
      to calculate the strain across the medial retinaculum and MPFL at 10 different
      degrees of knee flexion. This process was repeated in an MPFL injury model, as
      well as after standardized reconstruction of the MPFL using hamstring autograft
      performed in both 20 and 45 degrees of flexion. Averaged over all the measurement
      sites, the maximum principal strain (epsilon1) within the native MPFL increased
      rapidly from full extension to 120 degrees of flexion. The highest value of
      epsilon1 (87%) was observed at 120 degrees of knee flexion in the MPFL region.
      The largest change in strain occurred between 25 and 30 degrees (10% increase).
      The strain patterns in the knees reconstructed at 45 degrees of flexion more
      closely resembled the strain in the native state than did the strain in the knees
      reconstructed at 20 degrees. Strain within the native MPFL increases as the knee
      flexion angle increases, with the largest change occurring between 25 and 30
      degrees. Reconstruction of the MPFL at 45 degrees is preferable to reconstruction
      at 20 degrees as the strain across the medial retinaculum more closely resembles
      the strain in the native state. Knowledge of the strain across the MPFL should
      allow for more accurate reconstruction of the MPFL, potentially reducing the risk
      of patellar maltracking or cartilage overload. The proprietary VLS system used in
      this study has many potential uses for experimental analysis of strain in the
      human body. 

PMID- 24122437
TI  - Postoperative blood loss prevention in total knee arthroplasty.
AB  - Blood loss is a serious concern during lower extremity total joint arthroplasty
      with the estimated reduction in hemoglobin concentration known to vary between 2
      and 4 g/dL after total knee arthroplasty (TKA). Allogeneic transfusions are
      commonly used to treat the acute blood loss and postoperative anemia to diminish
      the potential cardiovascular risks in up to 50% of such cases with a high volume
      of blood loss. However, these transfusions are associated with the risks of
      immunologic reactions, immunosuppression, and infection transmission. Multiple
      blood-saving strategies have been developed to minimize blood loss, to reduce
      transfusion rates, to decrease complications, and to improve outcomes in the
      postoperative period. Currently, there are no clear guidelines on the blood
      management strategies adopted to lessen the blood loss associated with TKA. The
      aim of this study was to review the literature and provide a broad summary of the
      efficacy and complications associated with several blood-saving measures that are
      currently used in the postoperative period. Evidence suggests that simple
      techniques such as limb elevation, cryotherapy, compression dressings, and drain
      clamping may reduce external drainage, however, whether these techniques lead to
      less allogeneic transfusions is currently debatable. Further research on using a
      combination of these strategies and their cost-effectiveness are needed. 

PMID- 24122438
TI  - Blood management strategies in total knee arthroplasty.

PMID- 24122439
TI  - Preoperative blood management strategies for total knee arthroplasty.
AB  - Elective total knee arthroplasty is frequently associated with considerable blood
      loss and a concomitant decline in hemoglobin postoperatively. This often leads to
      high rates of allogeneic transfusions, with reports of up to 69%, to treat
      postoperative anemia. Allogeneic blood transfusions have been shown to be an
      independent risk factor for increased adverse outcomes, such as prolonged length
      of hospital stay and postoperative infections. Although multiple preoperative
      blood management strategies have been proposed, there are no concise guidelines,
      as few studies have compared the relative efficacy of these techniques. The aim
      of this review was to evaluate current evidence on the various preoperative blood
      management strategies for patients undergoing total knee arthroplasty and to
      provide an overview of the safety and efficacy of these practices. Specifically,
      we evaluated preoperative autologous blood donation, iron therapy, and
      intravenous erythropoietin. Current evidence suggests that these techniques
      independently may be effective at reducing the incidence of allogeneic blood
      transfusions, correcting preoperative, and preventing postoperative anemia.
      However, more studies are necessary to evaluate combination protocols, as well as
      the cost-effectiveness and safety of these practices as part of routine
      preoperative blood management for total knee arthroplasty. 

PMID- 24122441
TI  - Inactivation of the Carney complex gene 1 (PRKAR1A) alters spatiotemporal
      regulation of cAMP and cAMP-dependent protein kinase: a study using genetically
      encoded FRET-based reporters.
AB  - Carney complex (CNC) is a hereditary disease associating cardiac myxoma, spotty
      skin pigmentation and endocrine overactivity. CNC is caused by inactivating
      mutations in the PRKAR1A gene encoding PKA type I alpha regulatory subunit
      (RIalpha). Although PKA activity is enhanced in CNC, the mechanisms linking PKA
      dysregulation to endocrine tumorigenesis are poorly understood. In this study, we
      used Forster resonance energy transfer (FRET)-based sensors for cAMP and PKA
      activity to define the role of RIalpha in the spatiotemporal organization of the
      cAMP/PKA pathway. RIalpha knockdown in HEK293 cells increased basal as well as
      forskolin or prostaglandin E1 (PGE1)-stimulated total cellular PKA activity as
      reported by western blots of endogenous PKA targets and the FRET-based global PKA
      activity reporter, AKAR3. Using variants of AKAR3 targeted to subcellular
      compartments, we identified similar increases in the response to PGE1 in the
      cytoplasm and at the outer mitochondrial membrane. In contrast, at the plasma
      membrane, the response to PGE1 was decreased along with an increase in basal FRET
      ratio. These results were confirmed by western blot analysis of basal and PGE1
      induced phosphorylation of membrane-associated vasodilator-stimulated
      phosphoprotein. Similar differences were observed between the cytoplasm and the
      plasma membrane in human adrenal cells carrying a RIalpha inactivating mutation.
      RIalpha inactivation also increased cAMP in the cytoplasm, at the outer
      mitochondrial membrane and at the plasma membrane, as reported by targeted
      versions of the cAMP indicator Epac1-camps. These results show that RIalpha
      inactivation leads to multiple, compartment-specific alterations of the cAMP/PKA
      pathway revealing new aspects of signaling dysregulation in tumorigenesis. 

PMID- 24122443
TI  - Impact of model-based risk analysis for liver surgery planning.
AB  - PURPOSE: A model-based risk analysis for oncologic liver surgery was described in
      previous work (Preim et al. in Proceedings of international symposium on computer
      assisted radiology and surgery (CARS), Elsevier, Amsterdam, pp. 353-358, 2002;
      Hansen et al. Int I Comput Assist Radiol Surg 4(5):469-474, 2009). In this paper,
      we present an evaluation of this method. METHODS: To prove whether and how the
      risk analysis facilitates the process of liver surgery planning, an explorative
      user study with 10 liver experts was conducted. The purpose was to compare and
      analyze their decision-making. RESULTS: The results of the study show that model
      based risk analysis enhances the awareness of surgical risk in the planning
      stage. Participants preferred smaller resection volumes and agreed more on the
      safety margins' width in case the risk analysis was available. In addition, time
      to complete the planning task and confidence of participants were not increased
      when using the risk analysis. CONCLUSION: This work shows that the applied model
      based risk analysis may influence important planning decisions in liver surgery.
      It lays a basis for further clinical evaluations and points out important fields
      for future research.

PMID- 24122442
TI  - Reduced polyalanine-expanded Arx mutant protein in developing mouse subpallium
      alters Lmo1 transcriptional regulation.
AB  - Intellectual disability (ID) is a highly prevalent disorder that affects 1-3% of
      the population. The Aristaless-related homeobox gene (ARX) is a frequently
      mutated X-linked ID gene and encodes a transcription factor indispensable for
      proper forebrain, testis and pancreas development. Polyalanine expansions account
      for over half of all mutations in ARX and clinically give rise to a spectrum of
      ID and seizures. To understand how the polyalanine expansions cause the clinical
      phenotype, we studied mouse models of the two most frequent polyalanine expansion
      mutations (Arx((GCG)7) and Arx(432-455dup24)). Neither model showed evidence of
      protein aggregates; however, a marked reduction of Arx protein abundance within
      the developing forebrain was striking. Examining the expression of known Arx
      target genes, we found a more prominent loss of Lmo1 repression in Arx((GCG7)/Y)
      compared with Arx(432-455dup24/Y) mice at 12.5 and 14.5 dpc, stages of peak
      neural proliferation and neurogenesis, respectively. Once neurogenesis concludes
      both mutant mouse models showed similar loss of Lmo1 repression. We propose that
      this temporal difference in the loss of Lmo1 repression may be one of the causes
      accounting for the phenotypic differences identified between the Arx((GCG)7)and
      Arx(432-455dup24) mouse models. It is yet to be determined what effect these
      mutations have on ARX protein in affected males in the human setting. 

PMID- 24122444
TI  - Unmethylated and methylated CpG dinucleotides distinctively regulate the physical
      properties of DNA.
AB  - In eukaryotic cells, DNA has to bend significantly to pack inside the nucleus.
      Physical properties of DNA such as bending flexibility and curvature are expected
      to affect DNA packaging and partially determine the nucleosome positioning
      patterns inside a cell. DNA CpG methylation, the most common epigenetic
      modification found in DNA, is known to affect the physical properties of DNA.
      However, its detailed role in nucleosome formation is less well-established. In
      this study, we evaluated the effect of defined CpG patterns (unmethylated and
      methylated) on DNA structure and their respective nucleosome-forming ability. Our
      results suggest that the addition of CpG dinucleotides, either as a (CG)n stretch
      or (CGX8 )n repeats at 10 bp intervals, lead to reduced hydrodynamic radius and
      decreased nucleosome-forming ability of DNA. This effect is more predominant for
      a DNA stretch ((CG)5) located in the middle of a DNA fragment. Methylation of CpG
      sites, surprisingly, seems to reduce the difference in DNA structure and
      nucleosome-forming ability among DNA constructs with different CpG patterns. Our
      results suggest that unmethylated and methylated CpG patterns can play very
      different roles in regulating the physical properties of DNA. CpG methylation
      seems to reduce the DNA conformational variations affiliated with defined CpG
      patterns. Our results can have significant bearings in understanding the
      nucleosome positioning pattern in living organisms modulated by DNA sequences and
      epigenetic features.

PMID- 24122446
TI  - Hospitalizations of children with autism increased from 1999 to 2009.
AB  - We performed a retrospective analysis of hospital discharges for children with
      autism, in comparison to children with cerebral palsy, Down syndrome, mental
      retardation/intellectual disability, and the general population. Hospitalizations
      for autism increased nearly threefold over 10 years, especially at the oldest
      ages, while hospitalizations for the other groups did not change. Leading
      discharge diagnoses for each age group in children with autism included mental
      health and nervous system disorders. Older age, Caucasian ethnicity, and living
      in a region with a high number of pediatric beds predicted hospitalizations
      associated with mental health diagnoses. These findings underscore the need for
      comprehensive clinical services that address the complex needs of children with
      autism to prevent costly hospitalizations.

PMID- 24122445
TI  - Latest developments in the biology and management of uveal melanoma.

PMID- 24122447
TI  - Tumorigenesis in cells derived from induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells are an attractive source for potential cell
      replacement therapy. However, transplantation of differentiated products harbors
      the risk of teratoma formation, presenting a serious health risk. Thus, we
      characterized Nanog-expressing (undifferentiated) cells remaining after induction
      of differentiation by cytological examination. To induce differentiation of iPS
      cells, we generated embryoid bodies (EBs) derived from iPS cells carrying a Nanog
      green fluorescent protein(GFP) reporter and then injected GFP-positive and GFP
      negative EBs into nude mice. GFP-positive EB transplantation resulted in the
      formation of immature teratoma grade 3, but no tumors were induced by GFP
      negative EB. GFP positive cells revealed significantly lower cytoplasmic area and
      higher nucleus/cytoplasm ratio than those of GFP negative cells. Our results
      suggest that morphological analysis might be a useful method for distinguishing
      between tumorigenic and nontumorigenic iPS cells.

PMID- 24122448
TI  - Baseline serum C-reactive protein and death from colorectal cancer in the NHANES
      III cohort.
AB  - Several prospective studies suggest that C-reactive protein (CRP), a nonspecific
      serologic marker of inflammation, might be linked to risk of colorectal cancer
      (CRC), whereas others have reported null or protective effects. We analyzed data
      from 7,072 participants (50-85 years) in the U.S. National Health and Nutrition
      Examination Survey III (1988-1994), a nationally representative cohort (n =
      33,994; 2 months-85 years) with vital status follow-up to 2000. Hazard ratios
      (HRs) for mortality associated with baseline clinically raised (>=1.00 mg/dL) and
      intermediate (>=0.22-0.99 mg/dL) CRP levels were estimated using Cox proportional
      hazards regression controlling for CRC risk factors. There were 59 deaths from
      CRC, 106 from other obesity-related cancers (other-ORCs) and 1,130 from
      cardiovascular disease (CVD). Participants with clinically raised CRP at baseline
      were found to have a statistically significant greater risk of CRC death (HRs =
      2.36-2.47) in comparison to persons with undetected levels. HRs were lower for
      death from other-ORC and CVD (1.82, 95% CI 1.05-3.15; 1.53, 95% CI 1.29-1.81,
      respectively). Intermediate CRP level was associated with a nonsignificant 10-21%
      increased risk for CRC death. HR for CRC death was higher among persons with a
      normal BMI (2.16, 95% 0.96-4.87, p = 0.06) compared to those who were overweight
      (1.22, 95% CI 0.53-2.78) or obese (1.23, 95% CI, 0.37-4.08). A similar pattern
      was observed for waist circumference. This effect modification suggests that the
      impact of chronic inflammation may be independent of excess body fat. Future
      research is recommended to confirm emerging data that elevated serologic CRP
      might reflect underlying colonic inflammation. 

PMID- 24122449
TI  - Highlighting a pi-pi interaction: a protein modeling and molecular dynamics
      simulation study on Anopheles gambiae glutathione S-transferase 1-2.
AB  - Cytosolic insect theta class glutathione S-transferases (GSTs) have not been
      studied completely and their physiological roles are unknown. A detailed
      understanding of Anopheles gambiae GST (Aggst1-2) requires an accurate structure,
      which has not yet been determined. A high quality model structure of Aggst1-2 was
      constructed using homology modeling and the ligand-protein complex was obtained
      by the docking method. Molecular dynamics (MD) simulations were carried out to
      study conformational changes and to calculate binding free energy. The results of
      MD simulation indicate that Aggst1-2 undergoes small conformational changes after
      ligands dock to the protein, which facilitate the catalytic reaction. An
      essential hydrogen bond was found between the sulfur atom of glutathione (GSH)
      and the hydrogen atom of hydroxyl group in Ser9, which was in good agreement with
      experimental data. A pi-pi interaction between Phe204 and CDNB ligand was also
      found. This interaction seems to be important in stabilization of the ligand.
      Further study of binding free energy decomposition revealed a van der Waals
      interaction between two ligands that may play a key role in nucleophilic addition
      reaction. This work will be a good starting point for further determination of
      the biological role of cytosolic insect theta class GSTs and will aid the design
      of structure-based inhibitors.

PMID- 24122450
TI  - Tumor suppressor activity and inactivation of galanin receptor type 2 by aberrant
      promoter methylation in head and neck cancer.
AB  - BACKGROUND: There is accumulating evidence that galanin receptors (GALRs) may be
      tumor suppressors in head and neck squamous cell carcinoma (HNSCC). Promoter
      methylation status and gene expression were assessed in a large panel of head and
      neck primary tumors, based on the hypothesis that cytosine-guanine dinucleotide
      (CpG) hypermethylation might silence the galanin receptor 2 (GALR2) gene.
      METHODS: GALR2 expression was examined in a panel of cell lines by using
      quantitative reverse transcription polymerase chain reaction (RT-PCR). The
      methylation status of the GALR2 promoter was studied using quantitative
      methylation-specific PCR (Q-MSP). UM-SCC-1 was stably transfected to express
      GALR2. RESULTS: GALR2 expression was suppressed in UM-SCC cell lines, whereas
      nonmalignant cell lines exhibited stable expression. GALR2 methylation found in
      31 of 100 (31.0%) tumor specimens was significantly correlated with the
      methylation status of both GALR1 and Galanin. The observed GALR2 promoter
      hypermethylation was statistically correlated with a decrease in disease-free
      survival (log-rank test, P=.045). A multivariate logistic-regression analysis
      revealed a high odds ratio for recurring methylation of GALR2 and the gene pair
      GALR2 and Galanin, 8.95 (95% confidence interval, 2.29-35.03; P=.024) and 9.05
      (95% confidence interval, 1.76-46.50; P=.008), respectively. In addition,
      exogenous expression of GALR2 suppressed cell proliferation in UM-SCC-1 cells
      with hypermethylated Galanin and GALR2-proficient cell lines. CONCLUSIONS:
      Frequent promoter hypermethylation in association with prognosis, and growth
      suppression after re-expression, supports the hypothesis that GALR2 may act to
      suppress tumor activity. GALR2 is a potentially significant therapeutic target
      and prognostic factor for this cancer type.

PMID- 24122451
TI  - PI3K is involved in beta1 integrin clustering by PSGL-1 and promotes beta1
      integrin-mediated Jurkat cell adhesion to fibronectin.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial step of
      lymphocyte homing by interacting with P- or E-selectins expressed on activated
      endothelium cells. Besides, it also functions as a receptor to induce signals
      that increase integrin affinity to ligands and mediate cell adhesion to
      endothelium. Integrin is required for the second step of lymphocyte homing, whose
      activation has been reported tightly regulated by inside-out signals triggered by
      chemokines or the shear-stress generated during lymphocyte rolling on
      endothelium. However, the relationship between PSGL-1-triggered signals and
      integrin activation is not clear. In this study, we demonstrated that PSGL-1
      ligation induces beta1 integrin-mediated adhesion to fibronectin via regulation
      of both beta1 subunit clustering and conformation changes. Phosphoinositide 3
      kinase (PI3K) is required for PSGL-1-induced beta1 integrin clustering which
      ultimately regulates beta1 integrin-mediated Jurkat cell adhesion to fibronectin.
      However, PI3K is not involved in the conformation changes or increases in the
      total expression of beta1 integrin. Taken together, we found a novel signal
      pathway, PSGL-1-PI3K-beta1 integrin, demonstrating the cooperation between
      initial adhesion and subsequent arrest and stable adhesion.

PMID- 24122452
TI  - Concordance and diagnostic accuracy of vasodilator stress cardiac MRI and 320
      detector row coronary CTA.
AB  - Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas
      coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study
      was to determine concordance and accuracy of vasodilator stress CMR and coronary
      CTA in the same subjects. We studied 151 consecutive subjects referred to detect
      or exclude suspected obstructive coronary artery disease (CAD) in patients
      without known disease or recurrent stenosis or ischemia in patients with
      previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner.
      CTA was performed on a 320-detector row system. Subjects were followed for
      cardiovascular events and downstream diagnostic testing. Subjects averaged 56 +/-
      12 years (60% male), and 62 % had intermediate pre-test probability for
      obstructive CAD. Follow-up averaged 450 +/- 115 days and was 100% complete. CMR
      and CTA agreed in 92% of cases (kappa 0.81, p < 0.001). The event-free survival
      was 97 % for non-ischemic and 39% for ischemic CMR (p < 0.0001). The event-free
      survival was 99% for non-obstructive and 36% for obstructive CTA (p < 0.0001).
      Using a reference standard including quantitative invasive angiography or major
      cardiovascular events, CMR and CTA had respective sensitivities of 93 and 98 %;
      specificities of 96 and 96%; positive predictive values of 91 and 91%; negative
      predictive values of 97 and 99%; and accuracies of 95 and 97%. Non-ischemic
      vasodilator stress CMR or non-obstructive coronary CTA were highly concordant and
      each confer an excellent prognosis. CMR and CTA are both accurate for assessment
      of obstructive CAD in a predominantly intermediate risk population.

PMID- 24122454
TI  - Complex coronary artery fistula between distal branches of the left anterior
      descending coronary artery and a branch of celiac trunk.

PMID- 24122453
TI  - Development of a theory for generating regional cardiac perfusion images during
      coronary angiography in the coronary angiography lab.
AB  - The purpose of this study was to develop a novel theory and method for generating
      regional myocardial perfusion images using fluoroscopy in the coronary
      angiography lab. We modified the Kety model to introduce the Patlak plot method
      for two-dimensional fluoroperfusion (FP) imaging. For evaluation, seven porcine
      models of myocardial ischemia with stenosis in the left coronary artery were
      prepared. Rest and stress FP imaging were performed using cardiovascular X-ray
      imaging equipment during the injection of iopamidol via the left main coronary
      artery. Images were acquired and retrospectively ECG gated at 80 % of the R-R
      interval. FP myocardial blood flow (MBF) was obtained using the Patlak plot
      method applied to time-intensity curve data of the proximal artery and
      myocardium. The results were compared to microsphere MBF measurements. Time
      intensity curves were also used to generate color-coded FP maps. There was a
      moderate linear correlation between the calculated FP MBF and the microsphere MBF
      (y = 0.9758x + 0.5368, R2 = 0.61). The color-coded FP maps were moderately
      correlated with the regional distribution of flow. This novel method of first
      pass contrast-enhanced two-dimensional fluoroscopic imaging can quantify MBF and
      provide color coded FP maps representing regional myocardial perfusion.

PMID- 24122455
TI  - Combating iron deficiency in children.

PMID- 24122457
TI  - Morphological and compressional mechanical properties of freeze-dried mannitol,
      sucrose, and trehalose cakes.
AB  - A novel mechanical compression test has been developed which allows cake
      mechanical properties to be assessed quantitatively, and can be applied to
      fragile and moisture-sensitive freeze-dried (FD) cakes within the vials without
      sample preparation. FD mannitol, sucrose, and trehalose cakes, prepared from 5%
      aqueous solutions, exhibited linear compressive elastic behavior for small
      strains with apparent moduli of 25, 148, and 207 kPa, respectively. These
      materials exhibited brittle cracking/crushing failure of the cells over a wide
      strain range, with low crushing stresses from 11to 31 kPa for 0.15-0.25 strain.
      This technique is sensitive to differences in freezing conditions for sucrose
      formulations and the moisture content of sucrose cakes. The test highlights the
      rapid changes in cake mechanical properties occurring when moisture-sensitive
      excipients such as sucrose are briefly exposed to ambient humidity. Using
      established models for the compressive mechanical behavior of closed cellular
      solids, a method for predicting cell wall thickness is demonstrated. Three FD
      formulations gave predicted wall thicknesses of 1.1-1.6 MUm, consistent with
      scanning electron microscopy (SEM) images obtained. SEM determined that unit cell
      dimensions for all formulations were similar and it was concluded that if all
      other factors were identical, excipient choice plays a minor role in determining
      the pore shape/morphology.

PMID- 24122456
TI  - Information: theory, brain, and behavior.
AB  - In the 65 years since its formal specification, information theory has become an
      established statistical paradigm, providing powerful tools for quantifying
      probabilistic relationships. Behavior analysis has begun to adopt these tools as
      a novel means of measuring the interrelations between behavior, stimuli, and
      contingent outcomes. This approach holds great promise for making more precise
      determinations about the causes of behavior and the forms in which conditioning
      may be encoded by organisms. In addition to providing an introduction to the
      basics of information theory, we review some of the ways that information theory
      has informed the studies of Pavlovian conditioning, operant conditioning, and
      behavioral neuroscience. In addition to enriching each of these empirical
      domains, information theory has the potential to act as a common statistical
      framework by which results from different domains may be integrated, compared,
      and ultimately unified. 

PMID- 24122458
TI  - Using a shape prior for robust modeling of the mitral annulus  on 4D ultrasound
      data.
AB  - PURPOSE: Over 40,000 annuloplasty rings are implanted each year in the USA to
      treat mitral regurgitation. However, the used measuring techniques to select a
      suitable annuloplasty ring are imprecise and highly depending on the expert's
      experience. This can cause a re-occurrence of the mitral regurgitation or an
      annuloplasty ring dehiscence, and thus the necessity of a re-operation. We
      propose a method to create a 4D model of the mitral annulus from ultrasound data
      to enable precise measurement and patient-specific implant planning. METHODS: An
      initial mitral annulus model is placed interactively in the 4D image data by
      defining commissure points and the annulus plane for one time step in diastole
      and systole. The model is automatically optimized using distinct image features.
      A shape and pose prior of the mitral annulus is used to compensate for artifacts
      and to enforce a plausible anatomical morphology, while a temporal alignment
      ensures a natural motion of the 4D model. RESULTS: Ground truth data were created
      for 4D images of 42 patients with varying image quality. A parameter and shape
      prior training was performed on a third of the ground truth data, while the rest
      was used to validate the method. The average error of the resulting mitral
      annulus models was computed as 2.25 ( +/-0.38 ) mm. The average expert standard
      deviation was determined as 1.86 (+/-0.32 ) mm. CONCLUSION: The proposed method
      enables the 4D modeling of mitral annuli based on ultrasound data in less than 2
      min. The resulting models are comparable to manually delineated models and can be
      used for measurements of annular geometries and patient-specific annuloplasty
      treatment planning.

PMID- 24122461
TI  - My career as a cardiologist and the developmental history of coronary
      intervention in Japan.

PMID- 24122459
TI  - Antimicrobial hydrogels for the treatment of infection.
AB  - The increasing prevalence of microbial infections, especially those associated
      with impaired wound healing and biomedical implant failure has spurred the
      development of new materials having antimicrobial activity. Hydrogels are a class
      of highly hydrated material finding use in diverse medical applications such as
      drug delivery, tissue engineering, as wound fillers, and as implant coatings, to
      name a few. The biocompatible nature of many gels make them a convenient starting
      platform to develop selectively active antimicrobial materials. Hydrogels with
      antimicrobial properties can be obtained through the encapsulation or covalent
      immobilization of known antimicrobial agents, or the material itself can be
      designed to possess inherent antimicrobial activity. In this review we present an
      overview of antimicrobial hydrogels that have recently been developed and when
      possible provide a discussion relevant to their mechanism of action.

PMID- 24122460
TI  - Genetic variants in TNF-alpha promoter are predictors of recurrence in patients
      with squamous cell carcinoma of oropharynx after definitive radiotherapy.
AB  - The promoter variants of TNF-alpha, a major regulator of immune and inflammation
      responses, have been implicated in cancer development and prognosis. Thus, we
      investigated associations between four TNF-alpha promoter variants and risk of
      recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated
      associations of four TNF-alpha polymorphisms with risk of recurrence in a cohort
      of 846 patients with SCCOP. Log-rank test and multivariable Cox models were used
      to evaluate associations. Compared with patients with variant genotypes of the
      TNF-alpha -308 and TNF-alpha -863 polymorphisms, patients with common homozygous
      genotypes had worse disease-free survival (log-rank p = 0.0002 and p < 0.0001,
      respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3-2.8
      and HR, 1.9, 95% CI, 1.3-2.7, respectively) after multivariable adjustment.
      Furthermore, among patients with HPV16-positive tumors, those with common
      homozygous genotypes of the TNF-alpha -308 and -863 polymorphisms had worse
      disease-free survival (log-rank p = 0.005 and p = 0.007, respectively) and higher
      recurrence risk than patients with variant genotypes of these polymorphisms (HR,
      5.1, 95% CI, 1.4-18.4 and HR, 3.7, 95% CI, 1.5-9.1, respectively), while no such
      significant associations were found for TNF-alpha -857 or -1031 polymorphisms.
      Our findings suggest that TNF-alpha -308 and -863 polymorphisms may modulate the
      risk of SCCOP recurrence in patients with HPV16-positive tumors. However, larger
      studies are needed to validate these results. 

PMID- 24122462
TI  - Percutaneous coronary intervention in ST-segment elevation myocardial infarction.

PMID- 24122463
TI  - Transradial and slender percutaneous coronary intervention: less invasive
      strategy in PCI.
AB  - Although there is a discussion on the outcome between percutaneous coronary
      intervention (PCI) and bypass surgery, PCI is clearly superior to bypass surgery
      in terms of less invasiveness. One of the further less invasive strategy is
      transradial approach (TRI). There have been several limitations such as low
      backup force of guiding catheters. However, mechanics studies showed that the
      backup force does not relate to approach site but to catheter shape and size. The
      other strategy is slender PCI using a 5 Fr or less guiding catheter. The slender
      PCI has also several limitations, however, some of these limitations have been
      overcome using new slender devices and new slender specific techniques. In this
      article, current progress in this field using new devices is reviewed. The less
      invasive strategy such as TRI and slender PCI may be the future direction of PCI
      because they prevent complications and improve quality of life. 

PMID- 24122464
TI  - Bare metal stent implantation in large-sized unprotected left main coronary
      artery stenosis in the drug-eluting stent era.
AB  - Recently, drug-eluting stent (DES) has been recommended as the first choice in
      those patients who need stent implantation in unprotected left main coronary
      artery (ULMCA) stenosis. However, the long-term safety and efficacy of this
      procedure is still controversial. The objective of this study was to evaluate the
      safety and efficacy of bare metal stent (BMS) implantation in ULMCA stenting in
      the DES era. We implanted BMS (mainly 4 mm-diameter) in large-sized ULMCA after
      December 2004 when DES became available. The results of BMS implantation (n = 19)
      were compared with those of DES implantation (n = 39). There was no significant
      difference between the 2 groups regarding age, gender and coronary risk factors.
      Emergency procedures were more frequently performed in the BMS group than in the
      DES group (53% vs. 26%, p = 0.08). The initial mortality was 10.5% (n = 2) in the
      BMS group and 2.6% (n = 1) in the DES group (p = 0.25). There was no stent
      thrombosis, Q-wave myocardial infarction or emergent bypass surgery in either
      group during their hospital stay. The restenosis rate was 0% (n = 45) in both
      groups, and the target vessel revascularization rate was 5.9% in the BMS group
      (1/17) and 2.6% (1/38) in the DES group (p = 0.53). Therefore, there were no
      statistically significant differences in outcomes between the two study groups.
      These results indicate that BMS implantation in a large-sized ULMCA may be a safe
      and effective treatment even in the DES era. 

PMID- 24122465
TI  - Enhanced platelet activation following coronary stent implantation in patients on
      hemodialysis.
AB  - Hemodialysis ("HD") has been suggested as a risk factor for stent thrombosis.
      However, platelet function in HD patients after coronary stent implantation
      remains unclear. The aim of this study was to evaluate platelet function
      following coronary stent implantation in HD patients. A total of 10 HD and 31 non
      HD patients who underwent a first coronary stent implantation were studied. All
      patients received 100 or 200 mg of asprin and thienopiridine (either ticlopidine
      200 mg or clopidogel 75 mg) daily. Platelet function was assessed 2-6 weeks (21
      +/- 8 days) after stent implantation by: (1) platelet maximal aggregation, using
      light transmittance aggregometry; (2) platelet aggregation threshold index, which
      was defined as putative concentration of agonist giving 50% maximum aggregation
      using whole-blood aggregometry; and (3) platelet activation markers (PAC-1 and
      CD62p), using whole blood flow cytometry. There were no differences between the
      two groups in baseline and procedure characteristics, except for a greater
      prevalence of hypertension and calcification in the HD group. Early stent
      thrombosis and bleeding did not occur in either group. Although no differences in
      platelet maximal aggregation or whole-blood aggregation were observed, expression
      of PAC-1 (39.6 +/- 9.1 vs 24.2 +/- 13.2%) and CD62p (10.4 +/- 5.5 vs 5.4 +/-
      2.3%) were significantly increased in the HD group compared with the non-HD
      group. HD patients exhibited enhanced platelet activation after coronary stent
      implantation, but suppression of platelet aggregation was achieved by the current
      dual antiplatelet therapy. 

PMID- 24122466
TI  - Long-term outcome of percutaneous transluminal coronary intervention for chronic
      total occlusion in the BMS era in Japan.
AB  - To investigate the long-term outcome of Percutaneous transluminal intervention
      (PCI) for chronic total occlusion (CTO). The subjects were 606 patients (1,145
      lesions) who were treated for CTO between January 1996 and December 2003 at our
      institution. Among them, 436 patients with early success and confirmed patency at
      the CTO by follow-up coronary angiography after 6 months were classified as the
      patent group (Group P), while 170 patients without early success or with
      occlusion on follow-up angiography were classified as the occluded group (Group
      O). In April 2006 (mean: 660 +/- 602 days), the outcome of CTO was investigated
      and the major adverse cardiac events (MACE)-free rate was calculated.
      Multivariate analysis was performed to identify determinants of death. The early
      success rate was 76.4% before 2003 when Conquest guidewires were not available.
      However, it subsequently showed significant improvement to 89%. The cumulative
      survival rate was significantly higher for Group P (92%) than for Group O (64%)
      and the MACE-free rate (free from, death, bypass surgery, myocardial infarction,
      and revascularization) showed a similar trend. The cumulative survival rate of
      patients without myocardial viability in the territory of the vessel with CTO was
      significantly higher for Group P (88%) than for Group O (55%). The outcome was
      significantly worse for patients with occlusion of other vessels (90%) than for
      patients without additional occlusion (42%). It was significantly better when the
      left ventricular ejection fraction (LVEF) was >=40% than when the LVEF was <=40%
      (90 vs. 68%). Multivariate analysis identified occluded CTO, other vessel
      occlusion, low ejection fraction (EF), unimproved EF, and old age as determinants
      of death from CTO. If early success is obtained and patency is maintained, the
      long-term outcome after PCI for CTO is significantly better than when failure
      occurs Occluded CTO, other vessel occlusion, low EF, unimproved EF, and old age
      are important determinants of the outcome. 

PMID- 24122467
TI  - Predictive value of serum cystatin C, beta2-microglobulin, and urinary liver-type
      fatty acid-binding protein on the development of contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) is associated with prolonged hospitalization
      and adverse clinical outcomes. Useful predictors of CIN are necessary to minimize
      the risk of developing CIN. The purpose of this study was to identify the useful
      predictors of CIN. We prospectively measured serum cystatin C (CysC) and beta2
      microglobulin (beta2-MG), and urinary liver-type fatty acid-binding protein (L
      FABP), beta2-MG and N-acetyl-beta-D-glucosaminidase (NAG) before and 1 day after
      percutaneous coronary intervention (PCI) in 96 patients with stable angina who
      underwent elective PCI. The frequency of CIN was 5% (5/96). Baseline levels of
      serum beta2-MG (4.2 +/- 2.6 vs. 2.2 +/- 1.0 mg/L, p = 0.0007) and CysC (1.51 +/-
      0.52 vs. 1.11 +/- 0.34 mg/L, p = 0.013) were significantly higher in the CIN
      group. Urinary beta2-MG, NAG, and L-FABP levels became significantly elevated
      after PCI. Of these, the mean change of urinary L-FABP was significantly higher
      in the CIN group (25.2 +/- 31.5 vs. 8.9 +/- 16.3 ng/mL, p = 0.044). Univariate
      linear regression analyses showed that the change of urinary L-FABP correlated
      positively with the volume of contrast medium (r = 0.460, p < 0.0001). Receiver
      operating characteristic analysis showed that baseline serum beta2-MG exhibited
      75% sensitivity and 80% specificity at a cut-off point of >2.8 mg/L, and baseline
      serum CysC exhibited 75% sensitivity and 73% at a cut-off point of >1.26 mg/L for
      predicting CIN. In conclusion, baseline serum beta2-MG and CysC were useful
      predictors of CIN. The change of urinary L-FABP serves as an indicator of renal
      injury due to contrast medium and as an adjunct predictor of CIN. 

PMID- 24122468
TI  - Six-month clinical outcomes after below-the-knee angioplasty for critical limb
      ischemia in patients on hemodialysis.
AB  - To evaluate 6-month clinical outcomes after below-the-knee (BTK) angioplasty for
      critical limb ischemia (CLI) in patients on hemodialysis (HD). Subjects were 69
      serial patients (81 limbs, 123 vessels) who underwent percutaneous transluminal
      angioplasty (PTA) for primary treatment of infrapopliteal lesions in CLI from
      June 2004 to December 2008. Subjects were classified into two groups for the
      comparative study of clinical outcomes: the patients on HD: the HD group (35
      patients, 45 limbs, 71 vessels, 66 +/- 11 years) and the patients not on HD: the
      non-HD group (34 patients, 36 limbs, 52 vessels, 69 +/- 9 years). A non
      randomized retrospective comparative study was conducted to obtain clinical
      outcomes at 6 months. In clinical results at 6 months, a higher percentage of
      tendency toward repeat PTA for the treated leg in the HD group (28.9 vs. 11.1%, p
      = 0.059), but it was not statistically significant. There was no significant
      difference in the rate of major amputation (11.1 vs. 5.5%) between the two
      groups. However, the percentage of repeat PTA performed twice or more times (13.3
      vs. 0%, p = 0.031) and all-cause mortality (17.1 vs. 0%, p = 0.012) in the HD
      group was significantly higher than in the non-HD group. The HD group had a
      significantly lower rate of freedom from all-cause mortality, major amputation,
      or repeat PTA in the 6-month follow-up compared to the non-HD group, with the HD
      group 51.4% and the non-HD group 85.3% (logrank test p = 0.003). Although there
      are more HD patients requiring repeat revascularization compared to the general
      population, the 6-month outcomes of limb salvage after BTK angioplasty for CLI in
      HD patients were not significantly different from the general population. 

PMID- 24122469
TI  - Clinical and angiographic outcomes after bare metal stents implantation for the
      patients with acute ST-elevation myocardial infarction: insights from multicenter
      trials.
AB  - The general restenosis rate after emergent coronary stent implantation for ST
      elevation myocardial infarction (STEMI) patients in Japan has yet to be fully
      established. Totally 696 STEMI patients without left main disease were enrolled
      for either ASPARAGUS (22 centers) or VAMPIRE (23 centers) trial. Out of these,
      202 lesions in 202 patients with baseline and 6-month follow-up quantitative
      coronary angiography (QCA) data after emergent bare metal stent (BMS)
      implantation without either aspiration or distal protection devices were enrolled
      for this study. QCA was performed at an independent core laboratory. Minimal
      lumen diameter (MLD), reference diameter (RD) and diameter stenosis (DS) were
      estimated at pre, post and follow-up phase. Left ventricular ejection fraction
      was evaluated by quantitative left ventriculography. Six-month binary restenosis
      (DS >50%) rate and target lesion revascularization (TLR) were investigated. Six
      month binary restenosis and TLR was found in 39 (19.3%) and 32 (18.6%),
      respectively. In the patients with binary restenosis, smaller pre-RD (2.46 +/-
      0.54 vs. 2.68 +/- 0.73 mm, p = 0.03), post-MLD (2.08 +/- 0.54 vs. 2.34 +/- 0.52
      mm, p = 0.009), acute gain (1.90 +/- 0.49 vs. 2.13 +/- 0.61 mm, p = 0.001) and
      follow-up RD (2.44 +/- 0.67 vs. 2.71 +/- 0.63 mm, p = 0.03) were observed. When
      the lesions are divided into quartiles of pre-RD (<=2.16, 2.18-2.61, 2.62-3.11,
      >=3.12 mm), the binary restenosis rates were 26, 25.5, 16 and 10%, and TLR rate
      were 19.5, 29.6, 13.6 and 12%, respectively. RD was smaller at pre and follow-up
      than post phase (pre: 2.64 +/- 0.71 mm; post: 2.89 +/- 0.57 mm; follow-up: 2.66
      +/- 0.64 mm; pre vs. post: p < 0.001; post vs. follow-up: p = 0.001; pre vs.
      follow-up: p = 1.00). In this study cohort, the binary restenosis and TLR rate
      were considerable in patients with BMS for STEMI. The decrement of RD at follow
      up period was common and it indicates that vessel shrinkage post PCI for acute
      myocardial infarction may be a myth. TLR rate was more than the binary restenosis
      rate in two quartiles of pre-RD. Robust guideline regarding stent type and
      revascularization for STEMI patients should be established. 

PMID- 24122470
TI  - Hyperuricemia as a risk factor for progressive renal insufficiency after coronary
      intervention in patients with chronic kidney disease.
AB  - The development of renal insufficiency after percutaneous coronary intervention
      (PCI) is associated with increases in morbidity and mortality. Recent studies
      have reported that hyperuricemia (HU) results in hypertension, intrarenal
      vascular disease, and renal injury. We postulated that HU contributes to
      progressive renal disease after PCI. We studied 139 patients with chronic kidney
      disease (CKD) undergoing elective PCI including 59 HU patients. We assessed the
      relationship between HU and the development of renal insufficiency after PCI by
      estimating traditional contrast-induced nephropathy (CIN) and persistent
      postprocedural nephropathy (PPN) defined as an increase in creatinine >=0.2 mg/dl
      of the baseline value 2 weeks after procedure. CIN and PPN were seen in 6.5 and
      28.8% respectively. The incidence of PPN was higher in HU patients than in non-HU
      patients (p < 0.001) although the incidence of CIN was not significantly
      different between the two groups. PPN was more frequently observed in
      hyperuricemic patients irrespective of association with hypertension (with and
      without hypertension, p < 0.001 and p = 0.034, respectively). By univariate
      analysis, HU and hypertension are associated with PPN although there was no
      significant predictor of CIN in this study. Multivariate analysis showed HU and
      hypertension were independent predictors of PPN. HU is a predictor of slow and
      mild development of renal insufficiency after PCI in patients with CKD. 

PMID- 24122471
TI  - Two-wire protection of side branches to prevent side branch occlusion during
      stent implantation for bifurcational lesions.
AB  - To prevent side branch occlusion during bifurcational lesion stenting, the
      placement of a wire in both the main branch and side branch is performed for
      "side-branch protection". However, this procedure does not always prevent side
      branch occlusion. A procedure for placing two wires in the side branch, called
      "two-wire protection of side branches", is considered to be more likely to
      prevent occlusion compared with one-wire protection of the side branch. We report
      on three cases in which "two-wire protection of side branches" was effectively
      performed during the stenting of bifurcational lesions. 

PMID- 24122472
TI  - Emergent thoracic aortic angioplasty and stenting for middle aortic syndrome in
      non-specific aortitis.
AB  - A 61-year-old Japanese male was admitted to hospital due to severe congestive
      heart failure and pre-renal failure with middle aortic syndrome. The patient was
      successfully treated with emergent aortic angioplasty and kissing stents
      implantation whilst in a hemodynamically unstable state. Our experience confirms
      that stenosis of the descending aorta when treated with catheter intervention may
      be palliative, however, it was a very effective method for life threatening
      clinical conditions in the short and mid-term and may be an alternative to
      surgery. 

PMID- 24122473
TI  - Successful treatment of spontaneous coronary bypass rupture using a
      polytetrafluoroethylene-covered stent.
AB  - A 57-year-old man with coronary bypass surgery experienced spontaneous rupture of
      a vein graft 16 months following his operation. Multislice computed tomography
      revealed a perforation of the saphenous vein graft to the obtuse marginal branch.
      3D imaging was useful for diagnosis and in planning treatment. Hesitation to
      perform surgical treatment occurred due to inflammation in the patient, therefore
      we successfully implanted a polytetrafluoroethylene-covered stent to occlude the
      site of perforation. The use of a covered stent for a patient showing clear
      leakage of dye during angiography should be considered as an alternative to
      surgical intervention for a ruptured vein. 

PMID- 24122474
TI  - "Staged" kissing stent placement under computed tomographic angiography guidance
      for a bilateral aortoiliac occlusion.
AB  - A 64-year-old female with chronic hemodialysis complained of a worsening of
      bilateral intermittent claudication. Computed tomographic angiography (CTA)
      demonstrated severe calcified bilateral aortoiliac occlusions. The kissing stent
      placement was therefore attempted: A 10 * 60 mm SMART stent was placed into the
      right aortoiliac lesion at the 1st session, and a 10 * 60 mm SMART stent was
      placed into the left aortoiliac lesion parallel with the previous SMART stent at
      the 2nd session, thus completing the "staged" kissing stent placement. CTA
      indicated the penetrating point in the calcified plaque clearly, and this case
      suggested the usefulness of CTA guided percutaneous peripheral intervention. 

PMID- 24122475
TI  - A case of coronary lesion with lotus root appearance treated by percutaneous
      coronary intervention with intravascular ultrasound guidance.
AB  - A 66-year-old man underwent percutaneous coronary intervention (PCI). Coronary
      angiography showed a diffuse lesion with lotus root appearance and severe
      stenosis in the left anterior descending artery (LAD). Multiple channels were
      observed by intravascular ultrasound (IVUS). Different channels were connected to
      the first diagonal branch, the first septal branch and LAD lumen separately. To
      prevent obstruction of side branches, we made connections to the branches from
      the main channel of LAD with tapered-tip guide wire, followed by balloon
      dilatation and stenting without side branch obstruction. IVUS findings were
      helpful for the PCI with a lotus root appearance lesion. 

PMID- 24122476
TI  - Fluorogen-activating-proteins as universal affinity biosensors for
      immunodetection.
AB  - Fluorogen-activating-proteins (FAPs) are a novel platform of fluorescence
      biosensors utilized for protein discovery. The technology currently demands
      molecular manipulation methods that limit its application and adaptability. Here,
      we highlight an alternative approach based on universal affinity reagents for
      protein detection. The affinity reagents were engineered as bi-partite fusion
      proteins, where the specificity moiety is derived from IgG-binding proteins
      Protein A or Protein G-and the signaling element is a FAP. In this manner,
      primary antibodies provide the antigenic selectivity against a desired protein in
      biological samples, while FAP affinity reagents target the constant region (Fc)
      of antibodies and provide the biosensor component of detection. Fluorescence
      results using various techniques indicate minimal background and high target
      specificity for exogenous and endogenous proteins in mammalian cells.
      Additionally, FAP-based affinity reagents provide enhanced properties of
      detection previously absent using conventional affinity systems. Distinct
      features explored in this report include: (1) unfixed signal wavelengths
      (excitation and emission) determined by the particular fluorogen chosen, (2) real
      time user controlled fluorescence on-set and off-set, (3) signal wavelength
      substitution while performing live analysis, and (4) enhanced resistance to
      photobleaching.

PMID- 24122477
TI  - Gender-related differences in kidney of rats with chronic renal failure.
AB  - Chronic renal failure is characterized by adaptive mechanisms secondary to the
      loss of functioning nephrons. Clinical and experimental studies suggest
      participation of gender-related hormones on renal function and progression of
      chronic renal failure. We evaluated the effect of castration on renal alterations
      in male and female Wistar control rats and after 30 days of chronic renal failure
      (CRF) induced by 5/6 nephrectomy. The CRF male group showed higher proteinuria.
      Glomerular hypertrophy was similar among groups. Podocyte morphology showed
      disorders of foot processes and thickening of the basement membrane in the CRF
      male group. The CRF female group showed fewer alterations compared to males.
      Castration changed the profile in CRF male animals and the filtration barrier was
      preserved. CRF males showed the presence of alfa-smooth muscle actin suggesting
      an early prefibrotic event in this group. After castration this phenomenon was
      not observed. Noteworthy, in females, castration exacerbated the presence of alfa
      smooth muscle actin. In summary, proteinuria was higher in males and appeared
      early in the course of CRF, probably contributing to fibrotic events. Data were
      influenced by gender suggesting that male sex hormones aggravate renal
      alterations.

PMID- 24122478
TI  - Intermittent hypoxia protects cerebral mitochondrial function from calcium
      overload.
AB  - Hypoxia leads to Ca(2+) overload and results in mitochondrial uncoupling,
      decreased ATP synthesis, and neuronal death. Inhibition of mitochondrial Ca(2+)
      overload protects mitochondrial function after hypoxia. The present study was
      aimed to investigate the effect of intermittent hypoxia on mitochondrial function
      and mitochondrial tolerance to Ca(2+) overload. Wistar rats were divided into
      control and intermittent hypoxia (IH) groups. The IH group was subject to hypoxia
      for 4 h daily in a hypobaric cabin (5,000 m) for 7 days. Brain mitochondria were
      isolated on day 7 following hypoxia. The baseline mitochondrial functions, such
      as ST3, ST4, and respiratory control ratio (RCR = ST3/ST4), were measured using a
      Clark-type oxygen electrode. Mitochondrial adenine nucleotide concentrations were
      measured by HPLC. Mitochondrial membrane potential was determined by measuring
      rhodamine 123 (Rh-123) fluorescence in the absence and presence of high Ca(2+)
      concentration (0.1 M), which simulates Ca(2+) overload. Our results revealed that
      IH did not affect mitochondrial respiratory functions, but led to a reduction in
      AMP and an increase in ADP concentrations in mitochondria. Both control and IH
      groups demonstrated decreased mitochondrial membrane potential in the presence of
      high Ca(2+) (0.1 M), while the IH group showed a relative higher mitochondrial
      membrane potential. These results indicated that the neuroprotective effect of
      intermittent hypoxia was resulted partly from preserving mitochondrial membrane
      potential, and increasing mitochondrial tolerance to high calcium levels. The
      increased ADP and decreased AMP in mitochondria following intermittent hypoxia
      may be a mechanism underlying this protection.

PMID- 24122479
TI  - Focal salvage therapy for locally recurrent prostate cancer: a review.
AB  - Objectives: To evaluate the current status of focal therapy as the salvage
      treatment option for patients with recurrent prostate cancer after established
      therapy (radiation, surgery) failure for localized tumor.?Methods: A MedLine
      search using specified search terms was done on December 23, 2011. This research
      rendered 346 papers related to High-Intensity Focused Ultrasound (HIFU), 644
      papers related to cryosurgery, 180 related to photodynamic therapy and 3 articles
      related to radio frequency ablation. Very few of these papers presented original
      outcome data and are included in the present review.?Results: No controlled trial
      was available for analysis. ?Conclusions: Salvage HIFU in patients with local
      recurrence of prostate cancer after radical EBRT indicate is a reasonable
      treatment option, but better patient selection criteria are needed. It is a
      promising treatment option for local recurrence after radiation therapy, with
      morbidity comparable with other forms of salvage treatment. The side effects are
      not negligible but comparable with other forms of salvage treatment. Photodynamic
      therapy is a new option that could be suitable for organ-confined PC recurrence
      after radiotherapy, but the data are very few.

PMID- 24122480
TI  - Shying away from a good thing: social anxiety in romantic relationships.
AB  - OBJECTIVES: To determine whether social anxiety covaries with satisfaction,
      social support, and intimacy in romantic relationships. METHOD: Undergraduates
      and their romantic partners (N = 163) completed self-report questionnaires.
      RESULTS: Higher social anxiety in women, but not men, was associated with
      wanting, receiving, and providing less support, based on self- but not partner
      report measures. Women higher in social anxiety also reported being less
      satisfied in their romantic relationships and self-disclosing less to romantic
      partners than women lower in social anxiety. Further, self-reported received
      support mediated the relationship between social anxiety and romantic
      relationship satisfaction in women. In both sexes, higher social anxiety was
      related to perceiving intimacy as riskier and romantic relationships as less
      emotionally intimate. CONCLUSIONS: Together, results suggest that social anxiety
      is associated with interpersonal difficulty even in established romantic
      relationships.

PMID- 24122481
TI  - Prevention 2.0: targeting cyberbullying @ school.
AB  - Although cyberbullying is characterized by worrying prevalence rates and
      associated with a broad range of detrimental consequences, there is a lack of
      scientifically based and evaluated preventive strategies. Therefore, the present
      study introduces a theory-based cyberbullying prevention program (Media Heroes;
      German original: Medienhelden) and evaluates its effectiveness. In a pretest
      posttest design (9-month interval), schools were asked to randomly assign their
      participating classes to either control or intervention group. Longitudinal data
      were available from 593 middle school students (M Age = 13.3 years, 53 % girls)
      out of 35 classes, who provided information on cyberbullying behavior as well as
      socio-demographic and psychosocial variables. While the present results revealed
      worrying prevalence rates of cyberbullying in middle school, multilevel analyses
      clearly demonstrate the program's effectiveness in reducing cyberbullying
      behavior within intervention classes in contrast to classes of the control group.
      Hence, this study presents a promising program which evidentially prevents
      cyberbullying in schools.

PMID- 24122482
TI  - Coping with racism: the impact of prayer on cardiovascular reactivity and post
      stress recovery in African American women.
AB  - BACKGROUND: Prayer is often used to cope with racism-related stress. Little is
      known about its impact on cardiovascular function. PURPOSE: This study examined
      how prayer coping relates to cardiovascular reactivity (CVR), post-stress
      recovery, and affective reactivity in response to racism-related stress. METHODS:
      African American women (n =81; mean age=20 years) reported their use of prayer
      coping on the Perceived Racism Scale and completed anger recall and racism recall
      tasks while undergoing monitoring of systolic and diastolic blood pressure (DBP),
      heart rate, heart rate variability (HRV), and hemodynamic measures. Prayer coping
      was examined for associations with CVR, recovery, and affective change scores
      using general linear models with repeated measures. RESULTS: Higher prayer coping
      was associated with decreased state stress and DBP reactivity during racism
      recall (p's<0.05) and with decreased DBP and increased HRV during racism recall
      recovery(p's<0.05). CONCLUSIONS: Coping with racism by utilizing prayer may have
      cardiovascular benefits for African American women.

PMID- 24122484
TI  - Effects of reinforcer magnitude on reinforced behavioral variability.
AB  - Eight pigeons were exposed to a two-component multiple schedule. In each
      component, four-peck sequences across left and right keys were reinforced
      according to a variability threshold contingency. In one condition, only
      infrequently occurring response sequences were reinforced in each component,
      thereby generating highly variable sequences. In a separate condition, when the
      variability threshold contingency was lenient in each component, sequences were
      much less variable. In each condition, reinforcer magnitude was manipulated
      across components, and the larger reinforcer magnitude produced less variability
      than the smaller reinforcer magnitude. These results suggest that larger
      reinforcers hinder the reinforcement of behavioral variability. The results are
      interpretable in terms of the larger reinforcer inducing a greater level of
      behavioral repetition, particularly as the time to reinforcement was approached.
      This effect may have implications for reinforcing behavioral variability in
      humans. 

PMID- 24122483
TI  - A novel HLA-DRalpha1-MOG-35-55 construct treats experimental stroke.
AB  - Chemoattraction of leukocytes into the brain after induction of middle cerebral
      artery occlusion (MCAO) increases the lesion size and worsens disease outcome.
      Our previous studies demonstrated that partial MHC class II constructs can
      reverse this process. However, the potential application of pMHC to human stroke
      is limited by the need to rapidly match recipient MHC class II with the beta1
      domain of the pMHC construct. We designed a novel recombinant protein comprised
      of the HLA-DRalpha1 domain linked to MOG-35-55 peptide but lacking the beta1
      domain found in pMHC and treated MCAO after 4 h reperfusion in humanized DR2
      mice. Infarct volumes were quantified after 96 h reperfusion and immune cells
      from the periphery and CNS were evaluated for expression of CD74 and other cell
      surface, cytokine and pathway markers. This study demonstrates that four daily
      treatments with DRalpha1-MOG-35-55 reduced infarct size by 40 % in the cortex,
      striatum and hemisphere, inhibited the migration of activated CD11b+CD45high
      cells from the periphery to the brain and reversed splenic atrophy. Furthermore,
      DRalpha1-MOG-35-55 bound to CD74 on monocytes and blocked both binding and
      downstream signaling of macrophage migration inhibition factor (MIF) that may
      play a key role in infarct development. The novel DRalpha1-MOG-35-55 construct is
      highly therapeutic in experimental stroke and could be given to all patients at
      least 4 h after stroke onset without the need for tissue typing due to universal
      expression of DRalpha1 in humans.

PMID- 24122485
TI  - Oxygen allows Shewanella oneidensis MR-1 to overcome mediator washout in a
      continuously fed bioelectrochemical system.
AB  - Many bioelectrochemical systems (BESs) harness the ability of electrode-active
      microbes to catalyze reactions between electrodes and chemicals, often to perform
      useful functions such as wastewater treatment, fuel production, and biosensing. A
      microbial fuel cell (MFC) is one type of BES, which generates electric power
      through microbial respiration with an anode as the electron acceptor, and
      typically with oxygen reduction at the cathode to provide the terminal electron
      acceptor. Oxygen intrusion into MFCs is typically viewed as detrimental because
      it competes with anodes for electrons and lowers the coulombic efficiency.
      However, recent evidence suggests that it does not necessarily lead to lower
      performances-particularly for the model organism Shewanella oneidensis MR-1.
      Because flavin-mediated electron transfer is important for Shewanella species,
      which can produce this electron shuttle endogenuously, we investigated the role
      of flavins in the performance of pure-culture BESs with S. oneidensis MR-1 with
      and without oxygen. We found that oxygen increases current production more than
      twofold under continuously fed conditions, but only modestly increases current
      production under batch-fed conditions.We hypothesized that oxygen is more
      beneficial under continuously fed conditions because it allows S. oneidensis to
      grow and produce flavins at a faster rate, and thus lowers flavin washout. Our
      conclusions were supported by experiments with a flavin-secretion deficient
      mutant of S. oneidensis.

PMID- 24122486
TI  - Racial parities in outcomes after radiotherapy for head and neck cancer.
AB  - BACKGROUND: Although black patients experience worse outcomes after treatment for
      squamous cell carcinoma of the head and neck (HNSCC), these conclusions were
      based on populations in which blacks comprised a minority of patients. The
      objective of the current study was to determine the impact of race on outcomes in
      patients with HNSCC who received radiotherapy at an institution in which blacks
      comprised the majority of patients. METHODS: In this retrospective cohort study,
      the authors reviewed 366 black patients and 236 white patients who had
      nonmetastatic HNSCC for which they received radiotherapy between 1990 and 2012.
      The primary study outcome measures were locoregional control, freedom from
      distant metastasis, progression-free survival, and overall survival. RESULTS: The
      median follow-up was 18.3 months for all patients. The 2-year locoregional
      control rate was 71.9% for black patients compared with 64.2% for white patients
      (hazard ratio, 0.72; P=.03). There was no difference between blacks and whites
      regarding 2-year freedom from distant metastasis, progression-free survival, or
      overall survival. Among the patients who had stage III through IVB disease,
      blacks and whites had similar outcomes. On multivariate analysis, race was not
      statistically significant for locoregional control, freedom from distant
      metastasis, progression-free survival, or overall survival. Despite these similar
      outcomes, black patients had worse socioeconomic factors and increased
      comorbidities but had similar treatment compliance compared with white patients.
      CONCLUSIONS: With more adverse prognostic factors, black patients experienced
      oncologic outcomes similar to the outcomes of white patients after receiving
      radiotherapy for HNSCC. The current data suggest that centers that treat large
      percentages of minority patients who receive radiotherapy for HNSCCs may overcome
      existing health care disparities through improved treatment compliance.

PMID- 24122487
TI  - Design and synthesis of alpha-conotoxin GID analogues as selective alpha4beta2
      nicotinic acetylcholine receptor antagonists.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is an important target
      for currently approved smoking cessation therapeutics. However, the development
      of highly selective alpha4beta2 nAChR antagonists remains a significant
      challenge. alpha-Conotoxin GID is an antagonist of alpha4beta2 nAChRs, though it
      is significantly more potent toward the alpha3beta2 and alpha7 subtypes. With the
      goal of obtaining further insights into alpha-conotoxin GID/nAChR interactions
      that could lead to the design of GID analogues with improved affinity for
      alpha4beta2 nAChRs, we built a homology model of the GID/alpha4beta2 complex
      using an X-ray co-crystal structure of an alpha-conotoxin/acetylcholine binding
      protein (AChBP) complex. Several additional interactions that could potentially
      enhance the affinity of GID for alpha4beta2 nAChRs were observed in our model,
      which led to the design and synthesis of 22 GID analogues. Seven analogues
      displayed inhibitory activity toward alpha4beta2 nAChRs that was comparable to
      GID. Significantly, both GID[A10S] and GID[V13I] demonstrated moderately improved
      selectivity toward alpha4beta2 over alpha3beta2 when compared with GID, while
      GID[V18N] exhibited no measurable inhibitory activity for the alpha3beta2
      subtype, yet retained inhibitory activity for alpha4beta2. In this regard,
      GID[V18N] is the most alpha4beta2 nAChR selective alpha-conotoxin analogue
      identified to date.

PMID- 24122489
TI  - Molecular biotypes for periodontal diseases?

PMID- 24122488
TI  - Molecular differences between chronic and aggressive periodontitis.
AB  - The 2 major forms of periodontitis, chronic (CP) and aggressive (AgP), do not
      display sufficiently distinct histopathological characteristics or
      microbiological/immunological features. We used molecular profiling to explore
      biological differences between CP and AgP and subsequently carried out supervised
      classification using machine-learning algorithms including an internal
      validation. We used whole-genome gene expression profiles from 310 'healthy' or
      'diseased' gingival tissue biopsies from 120 systemically healthy non-smokers, 65
      with CP and 55 with AgP, each contributing with >= 2 'diseased' gingival papillae
      (n = 241; with bleeding-on-probing, probing depth >= 4 mm, and clinical
      attachment loss >= 3 mm), and, when available, a 'healthy' papilla (n = 69; no
      bleeding-on-probing, probing depth <= 4 mm, and clinical attachment loss <= 4
      mm). Our analyses revealed limited differences between the gingival tissue
      transcriptional profiles of AgP and CP, with genes related to immune responses,
      apoptosis, and signal transduction overexpressed in AgP, and genes related to
      epithelial integrity and metabolism overexpressed in CP. Different classifying
      algorithms discriminated CP from AgP with an area under the curve ranging from
      0.63 to 0.99. The small differences in gene expression and the highly variable
      classifier performance suggest limited dissimilarities between established AgP
      and CP lesions. Future analyses may facilitate the development of a novel,
      'intrinsic' classification of periodontitis based on molecular profiling. 

PMID- 24122491
TI  - Greetings from the new Editor-in-Chief.

PMID- 24122490
TI  - The importance of molecular complexity in the design of screening libraries.
AB  - The one-dimensional model of Hann et al. (JChem Inf Comput Sci 41(3):856-864) has
      been extended to include reverse binding and wrap-around interaction modes
      between the protein and ligand to explore the complete combinatorial matrix of
      molecular recognition. The cumulative distribution function of the Maxwell
      Boltzmann distribution has been used to calculate the probability of measuring
      the sensitivity of the interactions as the asymptotic limits of the distribution
      better describe the behavior of the interactions under experimental conditions.
      Based on our model, we hypothesized that molecules of lower complexity are
      preferred for target based screening campaigns, while augmenting such a library
      with moieties of moderate complexities maybe better suited for phenotypic
      screens. The validity of the hypothesis has been assessed via the analysis of the
      hit rate profiles for four ChemBL datasets for enzymatic and phenotypic screens.

PMID- 24122492
TI  - The no-reflow phenomenon associated with percutaneous coronary intervention: its
      mechanisms and treatment.
AB  - In patients with acute coronary syndrome (ACS), the immediate therapeutic goal is
      to establish patency of the infarct-related artery and to achieve optimal
      myocardial tissue reperfusion. Coronary microvasculatures, however, are often
      damaged irreversibly due to myocardial ischemia and reperfusion, and flow to the
      previously ischemic myocardium is markedly reduced, a phenomenon known as the "no
      reflow phenomenon". In clinical settings, percutaneous coronary intervention
      (PCI) may accelerate embolization of plaque gruels and microthrombi to the
      microvessels, which further reduces tissue perfusion. The microvascular
      dysfunction attenuates the beneficial impact of PCI. The extent of the no-reflow
      phenomenon correlates with infarct size, and it has additional prognostic
      information. Patients with the no-reflow phenomenon have poor functional and
      clinical outcomes. Recent advances in imaging modalities have enabled diagnosis
      of the no-reflow phenomenon and assessment of the mechanisms of the microvascular
      dysfunction in patients. Use of pharmacological interventions and catheter-based
      devices to retrieve embolic materials have been proposed, and some of them are
      associated with improvement in clinical outcomes. Thus, we should keep in mind
      that only the achievement of successful myocardial perfusion is associated with
      better functional and clinical outcomes in patients with ACS. 

PMID- 24122493
TI  - Initial clinical experience with distal embolic protection using "Filtrap", a
      novel filter device with a self-expandable spiral basket in patients undergoing
      percutaneous coronary intervention.
AB  - We developed a new filter-type distal protection guide wire, Filtrap, that uses a
      polyurethane filter with 1834 100-MUm micropores covering the distal half of a
      spindle-shaped spiral Ni-Ti basket. The basket is 5 mm in diameter, self
      expandable, and is mounted at the distal end of the system. This study aimed to
      assess the usefulness and safety of Filtrap during percutaneous coronary
      intervention (PCI). Early angiographic and in-hospital outcomes were reviewed in
      14 patients, including 9 acute coronary syndrome patients, treated with Filtrap
      during PCI. All lesions were located in native coronary arteries but one was
      located in a saphenous vein graft. The Filtrap was successfully delivered and
      deployed distal to the lesion in 13 of 14 patients (93%). All PCI procedures
      including stent implantation were successfully completed except for 2 AMI
      patients, who ended up with Thrombolysis in Myocardial Infarction (TIMI) 2
      coronary flow. One of these 2 patients had a distal embolization which occurred
      after thrombectomy before Filtrap insertion. The mean time of device insertion
      was 9.4 +/- 3.2 min. Five patients showed transient no-reflow that was completely
      restored immediately with removal of the device. Embolic debris was entrapped in
      8 (62%) of these cases. All patients were free from in-hospital events except for
      one patient with a large anterior acute myocardial infarction who received an
      emergency surgery due to a free wall cardiac rupture. These results suggest that
      the Filtrap is a practical and safe device for embolic protection during PCI. 

PMID- 24122494
TI  - Impact of chronic kidney disease on clinical and angiographic results following
      implantation of sirolimus-eluting coronary stents.
AB  - Although sirolimus-eluting stent (SES) is effective to reduce restenosis, the
      effect of SES for patients with chronic kidney disease (CKD) has been ambiguous.
      SES were exclusively implanted into 304 lesions in 195 patients. Forty-seven
      percent of the patients had diabetes. Patients were divided into three groups by
      estimated glomerular filtration rate, CKD stage 0-2: 156 patients, 239 lesions;
      CKD stage 3-4: 21 patients, 37 lesions; and CKD stage 5: 18 patients, 28 lesions.
      Clinical follow-up data were available in 97% at 616 +/- 192 days. There was a
      statistically significant association between the stage of CKD and target lesion
      revascularization (TLR) (CKD 0-2: 2.7%, CKD 3-4: 5.3%, and CKD 5: 11.9%; P =
      0.011), and late lumen loss at 8 months (CKD 0-2: 0.13 +/- 0.25 mm, CKD 3-4: 0.27
      +/- 0.47 mm, and CKD 5: 0.37 +/- 0.61 mm; P = 0.0032). The frequency of clinical
      adverse events was also higher according to stages of CKD. In conclusion, stages
      of CKD proportionally correlated with TLR, late lumen loss and major adverse
      cardiac events following SES implantation. 

PMID- 24122495
TI  - Prediction of late restenosis after sirolimus-eluting stent implantation using
      serial quantitative angiographic and intravascular ultrasound analysis.
AB  - Although sirolimus-eluting stents (SESs) have shown to significantly reduce the
      incidence of restenosis, it remains unclear when the follow-up angiography should
      be performed after SES implantation. A total of 868 patients with 1,574 lesions
      were treated with SES. Of the 71 patients with 87 lesions were performed serial
      angiographic and intravascular ultrasound (IVUS) analysis (pre, post, 1st and 2nd
      follow-up). The first follow-up period was 7.9 +/- 3.5 months and the second
      follow-up was 18.9 +/- 7.7 months. Late restenosis (LR) was defined as diameter
      stenosis >=50% at second follow-up, which was <50% at first follow-up. A total of
      restenosis was documented in 69 patients with 89 lesions (5.7%) overall, 13
      lesions (3.2%) led to LR. Angiographic pattern of LR was predominately focal
      pattern. In LR group, late lumen loss by angiography was increased between 1st
      follow-up and 2nd-follow-up (0.69 +/- 0.41 mm in first follow-up and 1.98 +/-
      0.44 mm in second follow-up, p < 0.0001). Minimum lumen area (MLA) by IVUS had
      slightly decreased already in 1st-follow-up (6.07 +/- 2.31 mm(2) in post
      procedure and 4.71 +/- 2.05 mm(2) in 1st-follow-up, p = 0.098) and significantly
      decreased in 2nd-follow-up (6.07 +/- 2.31 mm(2) in post procedure and 1.71 +/-
      0.93 mm(2) in 2nd-follow-up, p < 0.0001). However, in each period, there were no
      significant difference in both late lumen loss and MLA in non-LR group. Neointima
      growth prolonged gradually over 1 year in LR group. These findings suggest that
      if neointimal proliferation is recognized in short-term-follow-up period, long
      follow-up should be needed. 

PMID- 24122496
TI  - Incidence of side-effects of dual antiplatelet therapy with clopidogrel and
      aspirin after coronary stent implantation.
AB  - There is little information about the incidence of the side-effects of
      clopidogrel in Japanese patients undergoing coronary stent implantation. The
      present study included 334 consecutive patients who were given clopidogrel (75 mg
      daily) after coronary stent implantation. Aspirin (100 mg daily) was used
      indefinitely. Clopidogrel was prescribed for at least 4 weeks in patients with
      bare metal stents and indefinitely in those with drug-eluting stents (DES). The
      duration of clinical follow-up was 164.7 +/- 139.0 days. Half of the patients
      underwent stenting because of acute myocardial infarction. DES were used in 38%
      of the patients. Definite early stent thrombosis occurred in one patient (0.31%).
      There was one definite late stent thrombosis (0.31%). Side-effects of the
      clopidogrel were observed in 16 patients (4.9%). Liver dysfunction occurred in
      seven patients (2.1%), skin rash in six (1.8%), and bleeding in three (0.9%).
      There was no neutropenia or thrombocytopenia. The results of this study show that
      prescribing clopidogrel as well as aspirin is a safe treatment for Japanese
      patients undergoing coronary stenting. 

PMID- 24122497
TI  - Clinical impact of self-expandable stent diameter after femoropopliteal stenting.
AB  - The optimal diameter of a self-expandable stent for femoropopliteal (FP) artery
      disease remains unclear. The aim of this study is to investigate the influence of
      stent diameter on the clinical outcome after FP stenting and to identify optimal
      stent diameter of self-expandable stent implantation. This study was a
      prospective observational study. Eighty patients who underwent successful self
      expandable stent implantation for FP disease were enrolled in this study. A
      commercially available self-expandable stent was used. The operator determined
      the type, diameter and length of the stent based on a visual estimate in
      angiography. A peak systolic velocity ratio >2.0 was defined as restenosis.
      Primary patency was defined as treated vessel without restenosis and repeat
      revascularization. Secondary patency was defined as target vessel which
      subsequently become totally occluded and is reopened by repeat revascularization.
      As a result, restenosis was found in 34 patients (42.5%) during the follow-up of
      24 months. In-stent restenosis was independently predicted by stent fracture
      [hazard ratio (HR) 2.6, p = 0.01], chronic total occlusion (HR 2.4, p = 0.02) and
      stent diameter *10/vessel diameter (S/V) ratio (HR 1.7, p = 0.04). Using receiver
      operator characteristic analysis, S/V ratio >1.30 best separated patients with
      and without in-stent restenosis. Primary and secondary patency was significantly
      lower in patients with S/V ratio >1.30 (85 vs. 44%, p = 0.002 and 90 vs. 65%, p =
      0.009, respectively). In conclusion, an S/V ratio was an independent predictor of
      in-stent restenosis after FP stenting, and it was also associated with the
      clinical outcome. 

PMID- 24122498
TI  - A novel intravascular ultrasound-guided percutaneous coronary angioplasty
      technique via the retrograde approach for chronic total occlusion.
AB  - The retrograde approach via native channels, mainly septal collaterals, has now
      become routine. However even after retrograde advancement of a catheter through a
      collateral channel, it is sometimes difficult to guide the catheter from a false
      lumen into the true lumen. We experienced 3 patients in whom the site for
      retrograde guidewire re-entry site from the chronic total occlusion was unclear,
      and intravascular ultrasound (IVUS) was useful for identifying the re-entry site.
      Here we report on this new technique, in which IVUS guides the retrograde
      guidewire to its re-entry site. 

PMID- 24122499
TI  - Moderate stenosis in left main trunk side branches treated with single sirolimus
      eluting stents should be observed without additional stenting.
AB  - The sirolimus-eluting stent (SES) has dramatically reduced restenosis in patients
      with most types of coronary lesions, but bifurcation lesions remain a predictor
      of poor prognosis even in SES implantation. We aimed to determine the clinical
      outcomes of the left main trunk (LMT) side branches (SB) treated with a single
      SES strategy. SES implantation was successfully performed on 70 patients with LMT
      stenosis from August 2005 to August 2008. Of the 70 patients, 55 patients (59 SB)
      were treated with a single SES and a jailed SB. The 56 SB were divided into two
      groups according to percent diameter stenosis immediately following percutaneous
      coronary intervention (PCI) (Group 1: >50%; Group 2: <50%). Quantitative coronary
      angiography (QCA) data was evaluated. One year angiographic follow-up was
      performed on 23 patients (82.1%) in Group 1, and 21 patients (78.6%) in Group 2.
      Group 1 MLD was significantly larger at follow up than that post-PCI (0.9 +/- 0.4
      vs. 1.2 mm +/- 0.6 mm, p < 0.01). In Group 2, MLD and percent diameter stenosis
      did not change significantly. SB revascularization was not performed on either
      group at follow-up. Clinical outcomes of moderate stenosis in LMT SB treated with
      a single SES were acceptable, and stenosis progression within 1 year was minimal.
      We concluded that patients who present moderate residual stenosis in LMT SB with
      no presentation of ischemic symptoms should be observed rather than re-stented. 

PMID- 24122500
TI  - Conundrum: intervention for unprotected left main bifurcation coronary lesions.

PMID- 24122501
TI  - Removal of broken balloon mitral valvotomy coiled guidewire from giant left
      atrium using indigenous snare.
AB  - Balloon mitral valvotomy (BMV) is a safe and effective therapy for rheumatic
      mitral stenosis. During the procedure, the coiled portion of 0.025 in. stainless
      steel BMV guidewire broke off within the giant left atrium (LA). Attempts to
      retrieve the guidewire with various snares failed as it was moving freely within
      the voluminous LA. We describe a technique wherein the broken guidewire was
      retrieved with a snare made of 0.014 in. percutaneous transluminal coronary
      angioplasty guidewire. The mechanism and prevention of this complication and
      management options are discussed. 

PMID- 24122502
TI  - Very late stent thrombosis occurring simultaneously in sirolimus-eluting stents
      and bare-metal stent in three different coronary vessels.
AB  - A 36-year-old male was diagnosed with acute inferior myocardial infarction (MI).
      Emergent coronary angiography (CAG) revealed an occlusive lesion in the distal
      segment of the right coronary artery (RCA). The proximal and distal sites of the
      lesion were treated with a bare-metal stent (BMS) and a sirolimus-eluting stent
      (SES), respectively. Nine days later, he underwent elective percutaneous coronary
      intervention (PCI). Two SESs were implanted for the stenotic lesion in the left
      anterior descending artery (LAD), in addition to one SES for the mid-stenotic
      lesion in the left circumflex artery (LCX). Nine months after PCI, follow-up CAG
      revealed no restenosis at any stent-implanted site. Two years and 4 months after
      PCI, he was admitted to our hospital because of acute anterior MI. Emergent CAG
      revealed total thrombotic occlusion in the in-stent proximal site of LAD.
      Moreover, thrombotic lesions were also observed in in-stent sites: in both BMS of
      RCA and SES of LCX. He underwent intracoronary aspiration thrombectomy and plain
      old balloon angioplasty for LAD using intra-aortic balloon pumping. PCI for the
      thrombotic lesions in RCA and LCX was not performed. Seventeen days after the
      stent thrombosis, CAG revealed the complete disappearance of thrombi in LAD, LCX,
      and RCA. 

PMID- 24122503
TI  - Percutaneous coronary intervention for left main trunk ostial stenosis in a
      patient with Takayasu's arteritis.
AB  - Takayasu's arteritis with coronary artery involvement is a rare event especially
      in men. We will report on a male case of Takayasu's arteritis undergoing stent
      implantation for left main trunk (LMT) ostial stenosis. The case was that of a 25
      year-old man who had been diagnosed with Takayasu's arteritis but there was no
      significant large vessel involvement. He presented with effort angina and a
      multidetector computed tomography (MDCT) revealed severe ostial stenosis in the
      LMT. A coronary angiography confirmed this finding and a virtual histology
      intravascular ultrasound (VH-IVUS) showed fibrous thickening of the intima and
      media with little necrotic lipid core and calcification. We performed a bare
      metal stent implantation for this lesion. No restenosis was found in the MDCT at
      the 6 month follow-up. Our experience suggests that the VH-IVUS is useful for
      examining the gross structure and component of the coronary vascular wall and for
      determining the choice of treatment in patients with Takayasu's arteritis. 

PMID- 24122504
TI  - Dramatic improvement of rapidly progressing acute renal failure and severe
      hypertension after bilateral renal artery stenting.
AB  - In this case report, we describe an 83-year-old man with bilateral renal artery
      stenosis who had rapidly progressing acute renal failure and severe hypertension.
      These conditions improved dramatically after bilateral renal artery stenting.
      Renal artery stenosis can cause renal failure, hypertension, and heart failure,
      leading to a poorer life prognosis. If renal artery stenosis is found as a cause
      of acute renal failure, severe hypertension, or heart failure, it is useful to
      perform revascularization as soon as possible. Revascularization by stenting has
      a high success rate and is expected to improve the condition remarkably. 

PMID- 24122505
TI  - Effect of cilostazol on optimized standard antiplatelet therapy in a patient with
      a cytochrome P450 2C19 *2/*2 genotype.
AB  - A 54-year-old man with acute coronary syndrome underwent primary percutaneous
      coronary intervention (PCI) to implant a bare metal stent. Three weeks later, a
      subclinical in-stent thrombus was found at staged PCI despite dual antiplatelet
      therapy with aspirin and clopidogrel. Platelet function tests revealed high post
      treatment platelet reactivity, indicating an inadequate response to clopidogrel.
      The patient's cytochrome P450 2C19 genotype was *2/*2. Cilostazol at 200 mg/day
      was initiated in addition. Three months later, platelet inhibition was enhanced,
      and no thrombus was detectable by coronary angiography. Our experience suggests
      that triple antiplatelet therapy with cilostazol as well as aspirin and
      clopidogrel could prevent stent thrombosis with improved clopidogrel
      responsiveness. 

PMID- 24122506
TI  - Intravascular ultrasound-guided percutaneous coronary interventions with minimum
      contrast volume for prevention of the radiocontrast-induced nephropathy: report
      of two cases.
AB  - Radiocontrast-induced nephropathy (CIN) is one of the most serious complications
      of percutaneous coronary interventions (PCI). The prevention of PCI-related CIN
      for chronic kidney disease (CKD) patients has not been established yet. The
      intravascular ultrasound (IVUS) is commonly used as an imaging device during PCI.
      We performed IVUS-guided PCI while only using fluoroscopic imaging and without
      administering any routine contrast dye injection during the procedures. All
      patients underwent a baseline coronary angiography prior to the elective PCI.
      During the PCI, all the following procedures were done with X-ray fluoroscopic
      imaging without or with a minimized contrast dye injection: the engagement of the
      guiding catheter, insertion of the coronary guidewire, insertion of the IVUS
      catheter, the stent deployment and the post-dilatation. The diameter and the
      length of the balloon and the stent were determined according to the pre
      procedural IVUS findings, and the end point of the stent dilatation was also
      judged according to the acquired minimal cross-sectional area of the stent. Here
      we report our findings from two cases representative of IVUS-guided minimum
      contrast PCI in which the volumes of contrast dye during the procedure were 5 and
      4 ml, respectively. No CIN occurred after either procedure. The IVUS-guided
      minimum contrast PCI could be a promising option for the prevention of CIN after
      PCI. 

PMID- 24122507
TI  - Achievement of competency in endoscopic sinus surgery of otolaryngology
      residents.
AB  - OBJECTIVES/HYPOTHESIS: The goal of our study is to identify the number of
      Endoscopic Sinus Surgery (ESS) cases required to obtain competency in ESS, using
      a previously validated assessment tool. STUDY DESIGN: Prospective observational
      study. METHODS: Seventeen residents from Johns Hopkins Otolaryngology-Head & Neck
      Surgery residency program were evaluated as they performed endoscopic sinus
      surgery in the operating room. Global and checklist parts of the ESS instrument
      were used for assessment purposes. Items on the tool were grouped into three
      different milestones for analysis of data (Milestone 1 = Maxillary Antrostomy +
      Anterior Ethmoidectomy, Milestone 2 = Posterior Ethmoidectomy + Sphenoidostomy,
      Milestone 3 = Frontal Sinusotomy). Residents were deemed competent if they
      achieved a minimum score of 3 on a 5-point Likert scale on each step of the
      surgery. RESULTS: A total of 73 evaluations were completed for 17 residents
      (Postgraduate Level 2-5) by eight evaluators between 2009 and 2011. A 60%
      probability of achieving competency in performance of all milestones of ESS is
      obtained with performing 42 ESS procedures and the probability is increased to a
      100% with performance of 55 endoscopic sinus surgery procedures. On average it
      took residents 23 cases to become competent in performance of maxillary
      antrostomy and anterior ethmoidectomy. CONCLUSIONS: Our results suggest that it
      requires 42 ESS procedures to attain a 60% probability of competency in ESS.
      These results have implications for otolaryngology residency programs when
      developing curriculum and benchmarks for the training residents.

PMID- 24122508
TI  - Interlaboratory variation in the performance of liquid-based cytology: insights
      from the ATHENA trial.
AB  - Although it is recognized that cervical cytology is highly subjective, and that
      there is considerable interlaboratory variation in how slides are evaluated,
      little is known as to how this impacts the performance of cytology. In the ATHENA
      trial, liquid-based cytology specimens from 46,887 eligible women >=21 years of
      age were evaluated at four large regional US laboratories, providing a unique
      opportunity to evaluate the impact of interlaboratory variations on the
      performance of cervical cytology. All women with abnormal cytology (atypical
      squamous cells of undetermined significance or higher) were referred to
      colposcopy, as were all high-risk human papillomavirus (hrHPV)-positive women
      >=25 years of age and a random subset of those >=25 years of age who were
      negative by both hrHPV testing and cytology. Sociodemographics, risk factors for
      cervical disease, and prevalence of cervical intraepithelial neoplasia (CIN) were
      similar across the laboratories. There were considerable differences among the
      laboratories both in overall cytological abnormal rates, ranging from 3.8 to
      9.9%, and in sensitivity of cytology to detect CIN grade 2 or worse (CIN2+), from
      42.0 to 73.0%. In contrast, the hrHPV positivity rate varied only from 10.9 to
      13.4%, and the sensitivity of hrHPV testing from 88.2 to 90.1%. These
      observations suggest that hrHPV testing without cytology should be considered as
      the initial method for cervical cancer screening. 

PMID- 24122509
TI  - Simultaneous extraction of carotid artery intima-media interfaces  in ultrasound
      images: assessment of wall thickness temporal  variation during the cardiac
      cycle.
AB  - OBJECTIVES: The aim of this work is to present and evaluate a novel segmentation
      method for localizing the contours of the intima-media complex in the carotid
      artery wall through longitudinal ultrasound B-mode imaging. The method is used to
      investigate the association between atherosclerosis risk factors and the cyclic
      variation of the intima-media thickness during the heart beat. METHODS: The
      framework introduced is based on two main features. The first is a simultaneous
      extraction of both the lumen-intima and the media-adventitia interfaces, using
      the combination of an original shape-adapted filter bank and a specific dynamic
      programming scheme. The second is an innovative spatial transformation that eases
      the extraction of skewed and curved contours, and exploits the result from the
      previous image as a priori information, when processing the current image. The
      intima-media thickness is automatically derived from the estimated contours for
      each time step during the cardiac cycle. Our method was evaluated in vivo on 57
      healthy volunteers and 25 patients at high cardiovascular risk. Reference
      contours were generated for each subject by averaging the tracings performed by
      three experienced observers. RESULTS: Segmentation errors were 29 +/- 27 MUm for
      the lumen-intima interface, 42 +/- 38 MUm for the media-adventitia interface, and
      22 +/- 16 MUm for the intima-media thickness. This uncertainty was similar to
      inter- and intra-observer variability. Furthermore, the amplitude of the temporal
      variation in thickness of the intima-media layers during the cardiac cycle was
      significantly higher in at-risk patients compared to healthy volunteers (79 +/-
      36 vs. 64 +/- 26 MUm, p = 0.032). Conclusion: The method proposed may provide a
      relevant diagnostic aid for atherosclerosis screening in clinical studies.

PMID- 24122510
TI  - Involvement of spinal chemokine CCL2 in the hyperalgesia evoked by bone cancer in
      mice: a role for astroglia and microglia.
AB  - The hypernociceptive role played by the chemokine CCL2, and its main receptor,
      CCR2, in pathological settings is being increasingly recognized. We aimed to
      characterize the involvement of spinal CCL2 in the hyperalgesia due to the
      intratibial inoculation of fibrosarcoma NCTC 2472 cells in mice. The intrathecal
      (i.t.) administration of the CCR2 antagonist RS 504393 (1-3 MUg) or an anti-CCL2
      antibody inhibited tumoral hyperalgesia. No change in the expression of spinal
      CCR2 was detected by western blot, whereas immunohistochemical experiments
      demonstrated increased CCL2 staining at the superficial laminae of the spinal
      cord ipsilateral to the tumor. This spinal CCL2 does not seem to be released from
      nociceptors since CCL2 mRNA and CCL2 levels in DRGs, as measured by RT-PCR and
      ELISA, remain unmodified in tumor-bearing mice. In contrast, immunohistochemical
      assays demonstrated the spinal up-regulations of GFAP and Iba-1, respective
      markers of astroglia and microglia, and the expression of CCL2 in both types of
      glial cells at the superficial laminae of the spinal cord of tumor-bearing mice.
      Finally, since CCL2 could induce astroglial or microglial activation, we studied
      whether the blockade of CCR2 could inhibit the increased spinal glial expression.
      GFAP, but not Iba-1, up-regulation was reduced in tumor-bearing mice treated for
      3 days with i.t. RS 504393, indicating that spinal CCL2 acts as an astroglial
      activator in this setting. The participation at spinal level of CCL2/CCR2 in
      tumoral hypernociception, together with its previously described involvement at
      periphery, makes attractive the modulation of this system for the alleviation of
      neoplastic pain.

PMID- 24122511
TI  - Prediction of clinical drug-drug interactions of veliparib (ABT-888) with human
      renal transporters (OAT1, OAT3, OCT2, MATE1, and MATE2K).
AB  - Veliparib (ABT-888) is largely eliminated as parent drug in human urine (70% of
      the dose). Renal unbound clearance exceeds glomerular filtration rate, suggesting
      the involvement of transporter-mediated active secretion. Clinically relevant
      pharmacokinetic interactions in the kidney have been associated with OAT1, OAT3,
      OCT2, MATE1, and MATE2K. In the present study, interactions of veliparib with
      these transporters were investigated. Veliparib inhibited OAT1, OAT3, OCT2,
      MATE1, and MATE2K with IC50 values of 1371, 505, 3913, 69.9, and 69.5 MUM,
      respectively. The clinical unbound maximum plasma concentration of veliparib
      after single oral dose of 50 mg (0.45 MUM) is manyfold lower than IC50 values for
      OAT1, OAT3, OCT2, MATE1, or MATE2K. These results indicate a low potential for
      drug-drug interaction (DDI) with OAT1/3, OCT2, or MATE1/2K. Additional studies
      demonstrated that veliparib is a substrate of OCT2. In Oct1/Oct2 double-knockout
      mice, the plasma exposure of veliparib was increased by 1.5-fold, and the renal
      clearance was decreased by 1.8-fold as compared with wild-type mice,
      demonstrating that organic cation transporters contribute to the renal
      elimination in vivo. In summary, the in vitro transporter data for veliparib
      predicts minimal potential for an OAT1/3-, OCT2-, and MATE1/2K-mediated DDI given
      the clinical exposure after single oral dose of 50 mg.

PMID- 24122512
TI  - Expanding the boundaries: reconfiguring the demographics of the "typical" eating
      disordered patient.
AB  - Eating disorders have long been recognized as problems afflicting a narrow
      segment of select populations: Caucasian, adolescent or young adult women from
      high-income Western countries. This review highlights recent data that reexamine
      and revise this constricted view of eating disorders in two specific ways. First,
      data are steadily accumulating that document the increasing prevalence of eating
      disorders among younger and older individuals. Pre-pubertal children and women in
      middle and late adulthood are increasingly presenting for eating disorder
      treatment. Second, data from around the globe indicate that there is nothing
      uniquely "Western" about eating disorders. As highlighted in this review, eating
      disorders are a global health problem, and they are predictably on the rise in
      many parts of the world. The data are also clear that ethnic and racial minority
      groups and immigrants within North America are vulnerable to eating disorders.
      This growing knowledge base expands the boundaries of what has historically been
      considered the "typical" eating disordered patient and should raise awareness
      among health care providers of the needs of the broader community that is at risk
      for eating disturbances. 

PMID- 24122513
TI  - Understanding health constraints among rural-to-urban migrants in China.
AB  - The main purpose of this article is to examine the understanding and experience
      of health and health care among rural-to-urban migrants in China, and to explain
      the impact of the internal factors of migrants themselves and the external
      factors of their social environment. Understanding the perceptions and
      consciousness of health issues among migrants is crucial to prevention,
      intervention, and other health-related measures for the migrant population in
      China, but this has rarely been explored in studies. On the basis of a case study
      of a migrant community in Beijing, I explore the migrants' understandings of
      health and health care and analyze factors in the social environment, including
      exclusion from the social system and the possibility of health participation,
      exclusion from social relation networks, obstructed channels of health
      maintenance, and exclusion of crowd psychology, which impact heavily on their
      health understanding and health behavior. I argue that the internal and the
      external factors are linked together closely and interact as reciprocal
      causation. However, the migrants should not be seen as primarily responsible,
      because their poor understanding of health mainly results from the socioeconomic
      environment in which they live and work. 

PMID- 24122514
TI  - Understanding the experiences of hearing voices and sounds others do not hear.
AB  - In this article, we aim to contribute to the understanding of how people with
      mental illness experience hearing voices and sounds that others do not hear in
      daily life. We conducted in-depth interviews with 14 people and analyzed the
      interviews using a hermeneutic phenomenological approach. The themes we arrived
      at included the following: hearing someone else or myself, am I losing my mind?,
      and daily life recurrently dominated by opposing voices. Our overall
      understanding of how the voices and sounds were experienced in daily life was
      that the intentions of others resounded intrusively in the participants and
      disrupted their lives. The tones and contents of these perplexing perceptions
      echoed and amplified past, present, and future experiences and concerns. The
      results elucidate the value that exploring and attempting to understand people's
      daily life experiences of hearing voices and sounds might have for the voice
      hearer, his or her family, and health care providers. 

PMID- 24122515
TI  - The importance of optimism in maintaining healthy aging in rural Alaska.
AB  - Many Alaska Native Elders attended government-run boarding schools as children,
      were forbidden to speak their native language, and were forced to abandon their
      traditional subsistence lifestyle, yet they maintained an optimistic outlook on
      life and continued to age well. The Explanatory Model Interview Protocol was
      adapted to interview a purposive sample of Alaska Native Elders (n = 26) and
      grounded theory was used to develop a model of successful aging for Alaska Native
      Elders in Bristol Bay, Alaska. The theme of optimism was significant in the
      findings and was also found in each of the elements of successful aging, which
      were spirituality, emotional well-being, community engagement, and physical
      health. These four elements served as the foundation of the Model of Successful
      Aging. The Elders believed they were able to age successfully because they
      continued to be optimistic despite the challenges they faced (and are currently
      facing) in their communities. 

PMID- 24122516
TI  - Serious decisions: chronic conditions and choice of provider.
AB  - People with chronic health conditions combine conventional medical care with
      different complementary and alternative medicine (CAM) therapies for varying
      reasons. The data on which we drew to elucidate this derive from a large mixed
      methods study utilizing participant observation, in-depth interviews with 69
      people with type 2 diabetes mellitus and/or cardiovascular disease (CVD), and
      interviews with 20 health care providers. Although integrative practices are
      increasingly common, people make clear choices about and trade-offs between
      conventional medical care and CAM, often using CAM and prescribed pharmaceuticals
      in tandem for different conditions and distinct purposes and outcomes. As we
      illustrate, some people perceived type 2 diabetes and CVD as "too serious" for
      CAM treatment, but concurrently, many turned to CAM providers in appreciation of
      the serious attention these providers paid to their health-related concerns. 

PMID- 24122517
TI  - Using joint interviews in a narrative-based study on illness experiences.
AB  - Researchers are increasingly recognizing the usefulness of using joint interviews
      in research on illness experiences. However, there is limited discussion of joint
      interviews as a data collection method and of the factors that influence the
      choice to conduct individual or joint interviews. Although there are several
      advantages and disadvantages of both methods, the reasons that underpin the
      choice to use joint interviews are often not discussed in detail in the
      literature. Drawing from a narrative-based study on the experiences of living
      with motor neuron disease, we present joint interviews as a method sensitive both
      to the shared experience of illness and to the multiple perspectives around
      illness. Using interview excerpts, we discuss how through the use of joint
      interviews researchers can explore the intersubjective and heteroglossic nature
      of illness experiences. We argue that using joint interviews can offer valuable
      information about how couples coconstruct meaning and share experiences. 

PMID- 24122518
TI  - Purposing and repurposing harms: the victim impact statement and sexual assault.
AB  - The purpose of the victim impact statement (VIS) is to inform judges of victims'
      crime-related physical, psychological, and financial harms. Findings from
      interviews with Canadian sexual assault victims, advocates, victim services
      workers, and prosecutors (N = 37) demonstrated that harm descriptions were
      manipulated by victims and others in keeping with, and contrary to, VIS design.
      Victims and prosecutors purposed the VIS to inform court outcomes through harms
      claims and struggles over those claims. The repurposing of harms claims occurred
      through practices of strategic disclosure, intended to effect changes in others'
      behaviors, and harm peddling, the circulation of the VIS in nonsentencing arenas.
      Victims, adversaries, and criminal justice professionals engaged in harm peddling
      to obtain compensation, child custody, and parole delay. Implications of
      purposing and repurposing harms claims include novel opportunities and legal
      pitfalls for victims, varied responses by judges, and an expansion of social
      control over victims and offenders. 

PMID- 24122519
TI  - Of baby ducklings and clay pots: method and metaphor in HIV prevention.
AB  - In this article, I report on my decision to undertake a process of elicitation,
      development, and examination of metaphors for experiences of HIV prevention work
      in Burma/Myanmar. I cover the theoretical basis to that decision, my rationale
      for using metaphor elicitation as method when researching the rhetoric and
      practice of HIV prevention in Burma/Myanmar, the process I used, and some of the
      resultant metaphors. I also demonstrate that this process resulted in the opening
      up of a space for talking about HIV prevention that avoided recourse to standard
      prevention rhetoric, thereby enabling a new and deeper understanding of the gap
      between this rhetoric and people's actual practice or experience. 

PMID- 24122520
TI  - A picture is worth . . . ? Photo elicitation interviewing with formerly homeless
      adults.
AB  - We report on the use of photo elicitation interviewing (PEI) with 13 participants
      in a qualitative study of formerly homeless men and women with serious mental
      illness. Following a respondent-controlled approach, participants were asked to
      take up to 18 photographs visually portraying positive and negative aspects of
      their lives and to subsequently narrate the meaning of the photos in a one-on-one
      interview. Thematic analysis of the photos (N = 205) revealed two approaches to
      PEI: (a) a "slice of life" and (b) "then vs. now." Examples show how PEIs yielded
      deeper, more elaborate accounts of participants' lives compared to earlier verbal
      only interviews. Participants spoke of the benefits of PEI and preferred taking
      positive as opposed to negative photographs depicting their lives. Implications
      of PEI as a means of complementing verbal-only data are discussed. By moving away
      from predetermined content and meaning, respondent-controlled PEIs enhance
      empowerment and enable creativity. 

PMID- 24122521
TI  - Reporting levels of evidence.

PMID- 24122522
TI  - Screening entire health system ECG databases to identify patients at increased
      risk of death.
AB  - BACKGROUND: Current methods to identify patients at higher risk for sudden
      cardiac death, primarily left ventricular ejection fraction <=35%, miss ~80% of
      patients who die suddenly. We tested the hypothesis that patients with elevated
      QRS-scores (index of myocardial scar) and wide QRS-T angles (index abnormal
      depolarization-repolarization relationship) have high 1-year all-cause mortality
      and could be further risk stratified with clinical characteristics. METHODS AND
      RESULTS: We screened all 12-lead ECGs over 6 months at 2 large hospital systems
      and analyzed clinical characteristics and 1-year mortality. Patients with ECGs
      obtained in hospital areas with known high mortality rates were excluded. At the
      first hospital, QRS-score >=5 and QRS-T angle >=105 degrees  identified 8.0% of
      patients and was associated with an odds ratio of 2.79 (95% confidence interval,
      2.10-3.69) for 1-year mortality compared with patients below both ECG thresholds
      (13.9% versus 5.5% death rate). Left ventricular ejection fraction was >35% in
      82% of the former group of patients, and addition of ECG measures to left
      ventricular ejection fraction increased the discrimination of death risk
      (P<0.0001). At the second hospital, the odds ratio was 2.42 (1.95-3.01) for 1
      year mortality (8.8% versus 3.8%). Adjustment for patient characteristics
      eliminated interhospital differences. Multivariable adjusted odds ratio combining
      data from both hospitals was 1.53 (1.28-1.83). Increasing heart rate and chronic
      renal impairment further predicted mortality. CONCLUSIONS: Screening hospital ECG
      databases with QRS-scoring and QRS-T angle analysis identifies patients with high
      1-year all-cause mortality and predominantly preserved left ventricular ejection
      fraction. This approach may represent a widely available method to identify
      patients at increased risk of death.

PMID- 24122523
TI  - Social engagement and physical and cognitive health among American Indian
      participants in the health and retirement study.
AB  - Social engagement has many demonstrated benefits for aging non-Hispanic Whites in
      the U.S. This study examined data from the U.S. Health and Retirement Study to
      determine whether these benefits were similar among American Indians and Alaska
      Natives older than 50 years. Linear regression techniques were used to examine
      the associations between level of social engagement, scores for memory and mental
      status, and self-reported health among 203 American Indian and Alaska Native
      elders who participated in the Health and Retirement Study and had data available
      between 1998 and 2010. Level of social engagement was significantly associated
      with memory, mental status, and self-reported health. However, only the
      association of social engagement with mental status and self-reported health
      remained significant (p = 0.04 and p = 0.05, respectively) after adjusting for
      sociodemographic variables, number of known health conditions, and scores on the
      Center for Epidemiologic Studies Depression scale. Level of social engagement was
      not associated with patterns of decline across time in cognitive or physical
      health. Higher levels of social engagement are associated with better physical
      and cognitive functioning in American Indian and Alaska Native elders. Future
      studies should examine whether this association acts through cognitive
      stimulation, increase in physical activity resulting from social engagement, or
      access to resources that support physical and cognitive health.

PMID- 24122524
TI  - Health beliefs about chronic disease and its treatment among aging Cambodian
      Americans.

PMID- 24122525
TI  - Inequality in health status among older adults in Africa: the surprising impact
      of anti-retroviral treatment.

PMID- 24122526
TI  - New frontiers in circulating tumor cell analysis: A reference guide for
      biomolecular profiling toward translational clinical use.
AB  - Circulating tumor cells (CTCs) are now routinely isolated from blood, and
      measurement of CTC concentrations appears to correlate well with survival in
      patients with cancer. Interrogation of the molecular profile of CTCs for
      expression of protein biomarkers, genetic variants and gene expression provides
      opportunities to use this information to guide personalized treatment, monitor
      therapy and detect emerging resistance. However, successful application of
      profiling techniques requires analyses that deliver a reliable and clinically
      relevant representation of a patient's cancer as it changes with time. Here, we
      comprehensively review the current knowledge of therapeutically relevant
      biomarkers in isolated CTCs obtained by fluorescence imaging and genomic
      profiling approaches. The reviewed data support the notion that molecular
      profiling of CTCs will provide a reliable representation or surrogate index of
      tumor burden. Large-scale translational trials, many currently in progress, will
      provide critical data to progress CTC analysis toward wider clinical use in
      personalized treatment.

PMID- 24122527
TI  - Neuroimaging of Langerhans cell histiocytosis: a radiological review.
AB  - The neuroimaging of Langerhans cell histiocytosis (LCH), in most of the cases, is
      nonspecific and can vary depending on the location, especially as shown on
      magnetic resonance imaging (MRI). In the absence of a clinical history of LCH,
      isolated central nervous system (CNS) lesion presents a diagnostic challenge. LCH
      should be considered in the differential diagnosis of craniofacial tumors and
      neurodegenerative (ND) lesions of the brain. MRI is the modality of choice for
      investigating the CNS-LCH. Long-term follow-up with MRI is indicated in patients
      with ND-LCH. This retrospective study provides a comprehensive description of the
      spectrum of neuroimaging findings in patients with LCH, the underlying
      neuropathology, and follow-up study of the disease.

PMID- 24122528
TI  - Coronary angioscopy: current topics and future direction.
AB  - Disruption of vulnerable plaque and following thrombus formation are considered
      the main cause of acute coronary syndrome (ACS). Intracoronary angioscopy is an
      endoscopic technology that allows direct visualization of the coronary artery
      lumen and provides detailed information regarding plaque morphology in patients
      with coronary artery disease. The color and morphology of coronary plaque under
      angioscopy observation are proposed to be determinants for plaque stability.
      Angioscopically yellow plaque represents a thin-cap fibroatheroma, and is
      associated with a higher incidence of disruption and thrombus formation, and may
      be associated with future acute coronary syndromes. To circumvent the
      subjectivity of color interpretation, various quantitative methods have been
      proposed for identifying vulnerable plaques. Superior to other coronary imaging
      techniques such as VH IVUS and optical coherence tomography, angioscopy has
      impressively high sensitivity and specificity in detection of intraluminal
      thrombus. Angioscopy can also be used as an adjunctive technique during catheter
      intervention by directly visualizing the thrombus, stent struts and proliferating
      neointima. The time course and pattern of neointima coverage, as seen by
      angioscopy, various among different stent systems. Angioscopic assessment of
      serial changes after stent implantation may have potential benefits on patient's
      management after coronary stenting. 

PMID- 24122529
TI  - Angiographic and clinical outcomes of 100 consecutive severe calcified lesions
      requiring rotational atherectomy prior to sirolimus-eluting stent implantation in
      hemodialysis and non-hemodialysis patients.
AB  - Both severe calcified lesions and hemodialysis (HD) are predictors for high rates
      of restenosis, even in the drug-eluting stent era. We sought to investigate the
      angiographic and clinical outcome in a population of HD versus non-hemodialysis
      (non-HD) patients with severe calcified lesions requiring rotational atherectomy.
      One hundred consecutive lesions (28 lesions in the HD group, 72 in the non-HD
      group) from 82 patients (19 patients in the HD group, 63 in the non-HD group)
      requiring rotational atherectomy prior to sirolimus-eluting stent (SES)
      implantation were analyzed post-procedure and at 8 months. Clinical outcomes were
      assessed at 12 months. Inclusion criteria were calcified lesions with >270
      degrees  of superficial calcification on the intravascular ultrasound (IVUS),
      lesions that the IVUS could not cross, or undilatable lesions. There were no
      differences in patient characteristics except for age. Although both baseline and
      post-procedure angiographic findings were similar between the two groups, late
      loss in stented segment was significantly greater in the HD group than in the non
      HD group (HD vs. non-HD: 0.69 +/- 0.74 mm vs. 0.34 +/- 0.50; P = 0.030). Also,
      the HD group revealed significantly worse clinical outcomes. In conclusion, mid
      term results of highly complex, severely calcified lesions requiring rotational
      atherectomy in non-HD patients were permissible as compared to on-label lesions.
      However, in HD patients, both angiographic and clinical outcomes were still
      suboptimal in this lesion subset, even using SES. 

PMID- 24122530
TI  - Long-term safety and efficacy of low-dose clopidogrel in Japanese patients
      undergoing coronary stenting: a preliminary study.
AB  - This study evaluated long-term safety and efficacy of low-dose (50-mg)
      clopidogrel in Japanese patients undergoing coronary stenting. A total of 126
      patients with 153 lesions who consented to take a 50-mg maintenance dose of
      clopidogrel to prevent stent thrombosis were enrolled. The duration of clinical
      follow-up was 13.9 +/- 9.7 months. There was one early stent thrombosis (0.65%).
      Neither late nor very late stent thrombosis was observed in patients on
      clopidogrel plus aspirin. Side effects of clopidogrel were observed in 9 patients
      (7.1%). This preliminary study shows that 50-mg maintenance dose of clopidogrel
      may be acceptable in Japanese patients undergoing coronary stenting. 

PMID- 24122531
TI  - Potential difficulty for accurate categorization of drug-eluting stent thrombosis
      without coronary angiography: unignorable involvement of the cases with new onset
      acute myocardial infarction occurred in target vessels.
AB  - Very late stent thrombosis (VLST) is a major unresolved problem of drug-eluting
      stent (DES) implants. However, its actual incidence with respect to the
      distribution of DES-target vessel and accuracy of adjudicating stent thrombosis
      according to the ARC definition has not been yet adequately evaluated. We studied
      720 patients who had completed over 1 year from elective DES implantation. In
      this cohort, we extracted patients who present acute coronary syndrome (ACS) (n =
      3, 0.4%). The timing of ACS events was 17, 19, and 24 months after DES
      implantation. At the time of presentation, VLST was strongly suspected as the
      initial diagnosis, however, coronary angiography (CAG) confirmed the different
      culprit lesion from DES and clearly no thrombus within the DES. According to ARC
      definition, three probable stent thromboses in this cohort before CAG, however,
      no stent thrombosis was confirmed after the CAG. Thus, no stent thrombosis was
      confirmed among this study population. In the very late phase after DES
      implantation, new onset ACS is not at all extraordinary occurrence in the target
      vessels of previous DES implantation. However, stent thrombosis is often assumed
      without angiographic confirmation. The clinical possibility that non-stent
      thrombosis is incidentally diagnosed with stent thrombosis without angiographic
      confirmation should be considered within the current accepted definition of stent
      thrombosis. 

PMID- 24122532
TI  - A simple method preventing tangling of the guidewires during percutaneous
      coronary intervention for bifurcation lesions.
AB  - The aim was to examine the efficacy of the simple technique that reduces tangling
      of the guidewires by utilizing wet gauze during percutaneous coronary
      intervention with multiple guidewires. We defined "Critical tangle of the
      guidewires" as occurring when it became impossible to insert balloon catheters
      into the bifurcation lesion due to tangling of the guidewires without withdrawing
      and reinserting one of the guidewires. We compared the rate of the critical
      tangle of the guidewires between the group taking no special tangle precaution
      ("NP Group"), and the group taking the tangle precaution with the wet gauze
      ("Gauze Group"). Eighty-four patients were enrolled in the study and randomly
      assigned to either NP Group (n = 43) or Gauze Group (n = 41). The kissing balloon
      technique success was 42/43 (97.7%) versus 40/41 (97.6%), in NP Group and Gauze
      Group, respectively. The rate of critical tangle of the guidewires was
      significantly lower in Gauze Group (27.9 vs. 7.3%, p = 0.014). The manipulation
      of several guidewires utilizing gauze method will be a useful technique for
      reducing tangle of the guidewires during the procedure of kissing balloon
      technique. 

PMID- 24122533
TI  - Which DES is the most appropriate for very small target vessels? Experimental
      study of stent expandable performance with SES, PES, ZES and EES.
AB  - The restenosis rate of coronary stent has significantly decreased by implantation
      of the drug-eluting stent (DES). We often experienced the DES implantation for
      very small target vessels. The minimum size of DES in Japan and USA is 2.5 mm
      diameter, but there were no reports of the expandability of DESs for the very
      small target vessels with reference diameter <2.2 mm. We clarify the expandable
      performance of 2.5 mm-DESs for very small target vessels with reference diameter
      <2.2 mm in vitro and vivo study. We studied 3 pieces in each kind of DES
      (Sirolimus-eluting stent; SES, Paclitaxel-eluting stent; PES, Zotarolimus-eluting
      stent; ZES and Everolimus-eluting stent; EES) in vitro and vivo study of the
      porcine coronary artery with reference diameter <2.2 mm. By using the delivery
      balloon, each stent was initially dilated with 3.5 atm. And the pressure of 0.5
      atm. was applied until it reached the maximum pressure of 12 atm. The minimum
      pressure of the full expanded stent balloon was estimated as the minimum
      expandable pressure. The stent-inner diameter and area on each pressure were
      measured by IVUS. The average minimum expandable pressure (atm.) in vitro/vivo
      was 4.7/4.5 in SES, 7.2/6.8 in PES, 4.3/4.5 in ZES and 3.8/3.8 in EES. The inner
      diameter (mm) in vitro/vivo at minimum expandable pressure was 1.81 +/- 0.07/1.84
      +/- 0.05 in SES, 2.31 +/- 0.10/2.13 +/- 0.13 in PES, 2.41 +/- 0.13/1.98 +/- 0.31
      in ZES and 2.13 +/- 0.11/1.88 +/- 0.22 in EES. The stent inner-diameter (mm) of
      DESs at 8 atm. in vivo was 2.16/2.21/2.45/2.25 in SES/PES/ZES/EES. All kinds of
      DES could be delivered to very small target vessels with reference diameter <2.2
      mm at the minimum expandable pressure in vivo study, but the stent which
      presented adequate stent inner-diameter at 8 atm. was only SES. We have to
      implant the 2.5 mm-DESs for very small target vessels according to the data based
      on this expandability of DESs to bail out threatening occlusion due to coronary
      dissection or elastic recoil. 

PMID- 24122535
TI  - Novel transcatheter closure of internal iliac arteriovenous malformation.
AB  - Arteriovenous malformations arising from iliac arteries are rare anomalies.
      Percutaneous embolization of such malformations is an established therapeutic
      option. In this paper, we will describe a case, wherein the internal iliac artery
      feeding a giant arteriovenous fistula was closed using a patent ductus arteriosus
      (PDA) duct occluder percutaneously. The PDA duct occluder is a versatile device
      that can be used as an alternative to vascular plugs. 

PMID- 24122534
TI  - Clinical usefulness of the Driver((r)) stent in a retrospective, collaborative,
      multicenter, open-label study in Japanese real-world patients with coronary
      artery disease and the drug-eluting stent era.
AB  - The objectives of the present study were to determine predictors for target
      lesion revascularization (TLR) and to examine the clinical usefulness of the
      Driver((r)) stent (a cobalt alloy, modular-type) in Japanese patients with
      coronary artery disease. Data on 631 Japanese patients including 241 with stable
      angina and 361 with acute coronary syndrome-who had been implanted with the
      Driver((r)) stent (805 lesions) between August 2004 and February 2005-were
      collected retrospectively; 95.0 and 81.7% of these lesions were de novo and
      ACC/AHA classification B2/C type, respectively. Early angiography of 622 patients
      revealed 1) the preprocedural minimal lumen diameter (MLD) of 0.80 +/- 0.51 mm,
      with lesion lengths of 17.1 +/- 7.3 mm, and 2) the postprocedural MLD of 2.95 +/-
      0.55 mm, with MLD gains of 2.14 +/- 0.68 mm. At 270 days of clinical follow-up,
      the incidences of major adverse cardiac events (MACE), TLR, and early stent
      thrombosis (ST) were 18.8, 14.7, and 0.2%, respectively; the TLR rate decreased
      statistically significantly to 5.3 and 5.9% when implanting the Driver((r)) stent
      (3.5 and 4.0 mm) and by IVUS, respectively. Absence rate of diabetes mellitus,
      presence rate of AMI, presence rate of stent diameters of >=3.5 mm, and presence
      rate of IVUS-guided PCI showed lower TLR rates, with statistically significant
      differences. Uni- and multivariate analyses revealed that AMI and stent diameter
      (>=3.5 mm) are significant predictors for TLR (0.048 and 0.047, respectively),
      indicating that physicians are recommended to consider these variables when
      selecting candidate real-world patients for IVUS-guided PCI. 

PMID- 24122536
TI  - Remote infarction following percutaneous transluminal septal myocardial ablation:
      a report of two cases.
AB  - Percutaneous transluminal septal myocardial ablation is an established
      therapeutic option for symptomatic hypertrophic obstructive cardiomyopathy
      refractory to medical therapy. It is a safe procedure in experienced hands, but
      complications can occur. We report two cases of right ventricular myocardial
      infarction with inferior wall infarction that occurred after alcohol ablation of
      the septum. There are no standard guidelines regarding the most appropriate
      treatment strategy in this clinical scenario. The probable mechanism and
      management issues are discussed. 

PMID- 24122537
TI  - Combined treatment of trans-catheter coil embolization and modified covered stent
      implantation for ruptured saphenous vein graft aneurysm in patient with recurrent
      congestive heart failure.
AB  - This is the case of an 85-year-old woman, who developed a large aneurysm of the
      saphenous vein graft to the left circumflex coronary artery with a fistulous
      communication to the left atrium (LA) after being asymptomatic for 18 years post
      coronary artery bypass graft surgery. She suffered from recurrent congestive
      heart failure due to the extra abnormal flow and pressure overload to the LA.
      Because of high risk of re-operation, we performed a combined treatment of trans
      catheter coil embolization and modified covered stent implantation. After
      successful treatment, cardiac multi-slice computed tomography revealed almost
      completely decreased trans-fistulous flow to the LA. 

PMID- 24122538
TI  - Percutaneous coronary intervention in left main coronary artery disease in a
      patient with hemophilia B.
AB  - A 77-year-old male patient with the diagnosis of hemophilia presented himself at
      the cardiology clinic with unstable angina and a coronary angiography was
      planned. Factor IX was prepared before the procedure due to the risk of
      hemorrhage. Critical lesions were detected in the left main coronary artery
      (LMCA) and the procedure was performed on the LMCA in the same session. No
      complication of hemorrhage developed. Having rarely found in literature on any
      procedure on the LMCA without factor IX infusion we wished to report on this rare
      case of concurrent hemophilia B and acute coronary syndrome. 

PMID- 24122539
TI  - The potential of surgical strategy for incomplete stent apposition after
      implantation of a sirolimus eluting stent.
AB  - Sirolimus-eluting stents (SES) had been implanted in the left anterior descending
      artery of a 77-year-old male. Three years later, he was admitted for ST elevation
      myocardial infarction caused by stent thrombosis accompanied with incomplete
      stent apposition (ISA), and balloon angioplasty had to be performed on him.
      However, 6 months later, he was admitted for angina. There was progression of ISA
      and severe stenosis. Considering the allergic reaction to the polymer of the SES,
      or the risk of future stent thrombosis, coronary artery bypass grafting was
      selected for the revascularization. One year after the procedure, he felt no
      symptoms and the bypass graft was patent. A surgical strategy may be considered
      for recurrence of coronary events accompanied with ISA after stent implantation. 

PMID- 24122540
TI  - Intraoperative pulmonary artery stenting in aortoarteritis: a hybrid procedure.
AB  - A 40-year old male presented with history of dyspnea and recurrent syncope.
      Preliminary evaluation revealed findings suggestive of severe pulmonary
      hypertension. His echocardiogram revealed severe stenosis of the right pulmonary
      artery (RPA) with severe pulmonary hypertension, which was confirmed on 64-slice
      MSCT. On cardiac catheterization, the stenotic segment could not be crossed.
      Hence he underwent surgical reconstruction of the RPA. Post-operatively, he
      developed arterial desaturation and hypotension due to compression of the
      reconstructed segment by the ascending aorta. Subsequently, intraoperative direct
      stenting of the RPA was performed on a beating heart. Post-procedure there was a
      significant drop in right heart pressures which was sustained on 3-month follow
      up. The patient also had occlusion of the Coeliac and Superior Mesenteric
      arteries which was demonstrated on MSCT and angiography, suggesting
      Aortoarteritis as the etiology. This case illustrates an unusual presentation of
      Aortoarteritis and the role of hybrid procedures in situations where percutaneous
      intervention may not be technically feasible. 

PMID- 24122541
TI  - A new device for percutaneous mechanical thrombectomy in acute limb ischemia.
AB  - Acute limb ischemia caused by thromboembolism is an emergent and life-threatening
      disease. Rapid revascularization is inevitable to prevent major amputation. So
      far, thrombectomy by Fogarty balloon catheter has been a standard procedure for
      this emergent setting, though it is sometimes difficult to accomplish complete
      removal of thrombus within peripheral arteries. Herein, we report a case with
      acute limb ischemia which was successfully treated by a new mechanical
      thrombectomy device. This home-made device split thrombus into small pieces
      within arteries, and accelerated the efficiency of thrombus removal by an
      aspiration catheter thereafter. 

PMID- 24122542
TI  - Diagnosing dialysis access steal syndrome using skin perfusion pressure with an
      occlusion balloon.
AB  - A 76 year-old male with end-stage renal disease on hemodialysis (HD) presented
      with a non-healing ulcer on his right foot. His access site was the anterior
      tibial artery to great saphenous vein graft in the right lower distal extremity.
      Angiography showed so much flow through the dialysis access that distal extremity
      flow seemed inadequate. These symptoms are often caused by dialysis access steal
      syndrome (DASS), but many HD patients also have atherosclerotic disease. We used
      an occlusion balloon to temporarily occlude shunt flow and found that the skin
      perfusion pressure (SPP) increased significantly in both the dorsal and plantar
      arteries. Measuring the SPP under balloon occlusion allowed for a definitive
      diagnosis of DASS. 

PMID- 24122543
TI  - Relevance of intracranial hypertension control in the management of Cryptococcus
      neoformans meningitis related to AIDS.
AB  - PURPOSE: To evaluate the relationship between intracranial hyperpressure (HICP)
      and mortality in patients with cryptococcal meningitis related to AIDS (CMRA).
      METHODS: This was an observational retrospective study. Patients were treated
      according to the Infectious Diseases Society of America recommendations during
      the evaluation period (days 0, 3, 5 and after hospitalization). High intracranial
      pressure (HICP) was defined as ICP values of C250 mm H20. The correlation between
      HICP and mortality at each of the three time points considered was investigated.
      Statistical analysis on the descriptive parameters and on the probability of a
      "death" event (odds ratio, OR) at each of those three time points was performed
      using the statistical software program Epidata. RESULTS: Eighty patients were
      included in this study, of whom 53 (66.25 %) were male. The average age of the
      patients was 37.5 +/- 8.1 (range 22-55) years. The median CD4?lymphocyte cell
      count was 35 (range 0-367) cells/ml. Among the entire patient cohort, 53 patients
      had a favorable outcome, and the mortality rate was 33.75 %. At baseline (day 0),
      57 subjects (71.5 %) presented HICP, and these patients had a higher mortality
      rate than those with a normal ICP, but the difference did not reach statistical
      significance[OR 1.65, 95 % confidence interval (CI) 0.56-4.84]. On day 3, 41 of
      the patients presented HICP, and HICP at this timepoint was significantly
      associated with an increased risk of mortality (OR 4.35, 95 % CI 1.56-12.09). On
      day 5, 35(43.5 %) patients presented HICP, and HCIP at this time point was also
      significantly associated with higher mortality (OR 7.23, 95 % CI 2.53-20.14).
      CONCLUSION: The results of this study confirm an association between HICP and
      mortality in patients with CMRA and indicate that the control of ICP during the
      first 5 days of hospitalization is more important than managing HICP only at
      baseline.

PMID- 24122544
TI  - Early versus delayed post-operative bathing or showering to prevent wound
      complications.
AB  - BACKGROUND: Many people undergo surgical operations during their life-time, which
      result in surgical wounds. After an operation the incision is closed using
      stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of
      the surgical procedure and before the patient leaves the operating theatre, the
      surgeon covers the closed surgical wound using gauze and adhesive tape or an
      adhesive tape containing a pad (a wound dressing) that covers the surgical wound.
      There is currently no guidance about when the wound can be made wet by post
      operative bathing or showering. Early bathing may encourage early mobilisation of
      the patient, which is good after most types of operation. Avoiding post-operative
      bathing or showering for two to three days may result in accumulation of sweat
      and dirt on the body. Conversely, early washing of the surgical wound may have an
      adverse effect on healing, for example by irritating or macerating the wound, and
      disturbing the healing environment. OBJECTIVES: To compare the benefits (such as
      potential improvements to quality of life) and harms (potentially increased wound
      related morbidity) of early post-operative bathing or showering (i.e. within 48
      hours after surgery, the period during which epithelialisation of the wound
      occurs) compared with delayed post-operative bathing or showering (i.e. no
      bathing or showering for over 48 hours after surgery) in patients with closed
      surgical wounds. SEARCH METHODS: We searched The Cochrane Wounds Group
      Specialised Register;The Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE)
      (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non
      Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled
      Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP).
      SELECTION CRITERIA: We considered all randomised trials conducted in patients who
      had undergone any surgical procedure and had surgical closure of their wounds,
      irrespective of the location of the wound and whether or not the wound was
      dressed. We excluded trials if they included patients with contaminated, dirty or
      infected wounds and those that included open wounds. We also excluded quasi
      randomised trials, cohort studies and case-control studies. DATA COLLECTION AND
      ANALYSIS: We extracted data on the characteristics of the patients included in
      the trials, risk of bias in the trials and outcomes from each trial. For binary
      outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI).
      For continuous variables we planned to calculate the mean difference (MD), or
      standardised mean difference (SMD) with 95% CI. For count data outcomes, we
      planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software
      for performing these calculations. MAIN RESULTS: Only one trial was identified
      for inclusion in this review. This trial was at a high risk of bias. This trial
      included 857 patients undergoing minor skin excision surgery in the primary care
      setting. The wounds were sutured after the excision. Patients were randomised to
      early post-operative bathing (dressing to be removed after 12 hours and normal
      bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be
      retained for at least 48 hours before removal and resumption of normal bathing)
      (n = 442). The only outcome of interest reported in this trial was surgical site
      infection (SSI). There was no statistically significant difference in the
      proportion of patients who developed SSIs between the two groups (857 patients;
      RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs
      were 8.5% in the early bathing group and 8.8% in the delayed bathing group.
      AUTHORS' CONCLUSIONS: There is currently no conclusive evidence available from
      randomised trials regarding the benefits or harms of early versus delayed post
      operative showering or bathing for the prevention of wound complications, as the
      confidence intervals around the point estimate are wide, and, therefore, a
      clinically significant increase or decrease in SSI by early post-operative
      bathing cannot be ruled out. We recommend running further randomised controlled
      trials to compare early versus delayed post-operative showering or bathing.

PMID- 24122545
TI  - Study of a molecularly imprinted solid-phase extraction coupled with high
      performance liquid chromatography for simultaneous determination of trace
      trichlorfon and monocrotophos residues in vegetables.
AB  - BACKGROUND: Organophosphate pesticide residues are harmful to human health
      because of their potential mutagenic and carcinogenic properties. Therefore, it
      is of great importance to development an accurate and reliable analytical method
      to prevent their uncontrolled effects on environmental pollution and human
      health. RESULTS: This study reports a new method of molecularly imprinted solid
      phase extraction coupled with high-performance liquid chromatography (MISPE-HPLC)
      for simultaneous determination of two organophosphate pesticides residues. Two
      types of molecularly imprinted polymers (MIPs) were prepared using the
      trichlorfon and monocrotophos as the template molecule, respectively, methacrylic
      acid as the functional monomer, and ethylene glycol dimethacrylate as the cross
      linker. The recognition ability and adsorption-desorption dynamic of each
      imprinted polymer toward the trichlorfon or monocrotophos were characterised.
      Using the mixture of trichlorfon-MIP and monocrotophos-MIP (20:80, wt/wt) as
      solid-phase extraction sorbent, the factors affecting the pre-concentration on
      the analytes and the sensitivity of the MISPE-HPLC method were optimised. Under
      optimal condition, the linear range was 0.005-1.0 mg L-1. The limit of detection
      was 4.2 ug g-1 for trichlorfon, and 1.2 ng g-1 for monocrotophos. The peak area
      precision [Relative standard deviation (RSD)] for three replicates was 2.9-4.5%.
      The blank rape and cauliflower samples spiked with trichlorfon and monocrotophos
      at 0.05 and 0.005 ug g-1 levels were extracted and determined by this method with
      recoveries ranging from 88.5% to 94.2%. Moreover, this method was successfully
      applied to the quantitative detection of the trichlorfon and monocrotophos
      residues in leek samples. CONCLUSION: With good properties of high sensitivity,
      simple pre-treatment and low cost, this MISPE-HPLC method could provide a new
      tool for the rapid determination of multi-pesticide residues in the complicated
      food samples.

PMID- 24122546
TI  - Biochemical and molecular study of the influence of Amaranthus hypochondriacus
      flour on serum and liver lipids in rats treated with ethanol.
AB  - Hyperlipidemia and hepatic steatosis are frequent alterations due to alcohol
      abuse. Amaranth is a pseudocereal with hypolipidemic potential among other
      nutraceutical actions. Here we study the effect of Amaranthus hypochondriacus
      (Ah) seeds on serum and liver lipids, and the expression of genes associated to
      lipid metabolism and liver histology in male Wistar rats intoxicated with
      ethanol. The animals were divided into four groups; two groups were fed the
      American Institute of Nutrition 1993 for maintenance diet (AIN-93M), and the
      other two with AIN-93M containing Ah as protein source. One of each protein group
      received 20% ethanol in the drinking water, thus obtaining: CC (control casein),
      EC (ethanol casein), CAh (control Ah) and EAh (ethanol Ah). When comparing EAh vs
      . EC, we found a positive effect of Ah on lipids, preventing the increment of
      serum cholesterol (p <0.001), through the higher expression of the LDL receptor
      (p <0.001); and it also decreased free (p < 0.05) and esterified cholesterol (p
      <0.01) in liver, probably via the reduction of the 3-hydroxy-3-methylglutaryl
      coenzyme A reductase expression (p <0.001). We also observed that amaranth
      contributed to the decrease of fat deposits in liver, probably through the
      decrease in acetyl-CoA carboxylase alpha (p <0.01), glycerol-3-phosphate
      acyltransferase 1 (p <0.01) and diacylglycerol O-acyltransferase 2 (p <0.05)
      expression. The histological study showed a decrease in the fat deposits in the
      amaranth group when compared to casein; this is consistent with the biochemical
      and molecular parameters studied in this work. In conclusion, amaranth could be
      recommended to avoid the alterations in the lipid metabolism induced by alcohol
      and other harmful agents.

PMID- 24122547
TI  - Inhibition of key enzymes linked to obesity by preparations from Mediterranean
      dietary plants: effects on alpha-amylase and pancreatic lipase activities.
AB  - One of the most important strategy in the treatment of obesity includes the
      development of nutrient digestion and absorption inhibitors. Inhibition of
      digestive enzymes is one of the most widely studied mechanisms used to determine
      the potential efficacy of natural products as hypolipidemic and hypoglycaemic
      agents. In vitro studies here reported were performed to evaluate the inhibitory
      activity of five species(as hydroalcoholic extracts) of edible plants from
      Calabria region (Italy) on amylase and lipase by monitoring the hydrolysis of p
      NPC and the hydrolysis of glycoside bonds indigestible carbohydrate foods. The
      formulation obtained from Clematis vitalba L. exhibited the strongest inhibitory
      effect on pancreatic lipase (IC50=0.99 mg/ml) and on alpha-amylase(IC50=31.52
      MUg/ml). In order to explore metabolome production HPTLC analysis of the extracts
      was performed, revealing the predominance of (+/-)-catechin, caffeic acid and
      chlorogenic acid in C. vital ba formulation at concentration of 23.18+/
      3.14,13.63+/-0.65 and 18.88+/-0.76 mg/g, respectively. GC/MS analysis was used to
      identify fatty acids and terpene composition.

PMID- 24122549
TI  - Temperature dependence of amino acid side chain IR absorptions in the amide I'
      region.
AB  - Amide I' IR spectra are widely used for studies of structural changes in peptides
      and proteins as a function of temperature. Temperature dependent absorptions of
      amino acid side-chains that overlap the amide I' may significantly complicate the
      structural analyses. While the side-chain IR spectra have been investigated
      previously, thus far their dependence on temperature has not been reported. Here
      we present the study of the changes in the IR spectra with temperature for side
      chain groups of aspartate, glutamate, asparagine, glutamine, arginine, and
      tyrosine in the amide I' region (in D2O). Band fitting analysis was employed to
      extract the temperature dependence of the individual spectral parameters, such as
      peak frequency, integrated intensity, band width, and shape. As expected, the
      side-chain IR bands exhibit significant changes with temperature. The majority of
      the spectral parameters, particularly the frequency and intensity, show linear
      dependence on temperature, but the direction and magnitude vary depending on the
      particular side-chain group. The exception is arginine, which exhibits a
      distinctly nonlinear frequency shift with temperature for its asymmetric CN3H5(+)
      bending signal, although a linear fit can account for this change to within ~1/3
      cm(-1). The applicability of the determined spectral parameters for estimations
      of temperature-dependent side-chain absorptions in peptides and proteins are
      discussed.

PMID- 24122550
TI  - Multifrequency electrical impedance tomography using spectral constraints.
AB  - Multifrequency electrical impedance tomography (MFEIT) exploits the dependence of
      tissue impedance on frequency to recover an image of conductivity. MFEIT could
      provide emergency diagnosis of pathologies such as acute stroke, brain injury and
      breast cancer. We present a method for performing MFEIT using spectral
      constraints. Boundary voltage data is employed directly to reconstruct the volume
      fraction distribution of component tissues using a nonlinear method. Given that
      the reconstructed parameter is frequency independent, this approach allows for
      the simultaneous use of all multifrequency data, thus reducing the degrees of
      freedom of the reconstruction problem. Furthermore, this method allows for the
      use of frequency difference data in a nonlinear reconstruction algorithm. Results
      from empirical phantom measurements suggest that our fraction reconstruction
      method points to a new direction for the development of multifrequency EIT
      algorithms in the case that the spectral constraints are known, and may provide a
      unifying framework for static EIT imaging. 

PMID- 24122551
TI  - Augmented Lagrangian with variable splitting for faster non-Cartesian L1-SPIRiT
      MR image reconstruction.
AB  - SPIRiT (iterative self-consistent parallel imaging reconstruction), and its
      sparsity-regularized variant L1-SPIRiT, are compatible with both Cartesian and
      non-Cartesian magnetic resonance imaging sampling trajectories. However, the non
      Cartesian framework is more expensive computationally, involving a nonuniform
      Fourier transform with a nontrivial Gram matrix. We propose a novel
      implementation of the regularized reconstruction problem using variable
      splitting, alternating minimization of the augmented Lagrangian, and careful
      preconditioning. Our new method based on the alternating direction method of
      multipliers converges much faster than existing methods because of the
      preconditioners' heightened effectiveness. We demonstrate such rapid convergence
      substantially improves image quality for a fixed computation time. Our framework
      is a step forward towards rapid non-Cartesian L1-SPIRiT reconstructions. 

PMID- 24122552
TI  - Aggregates of alpha-chymotrypsinogen anneal to access more stable states.
AB  - Non-native protein aggregates present a variety of problems in fundamental and
      applied biochemistry and biotechnology, from quality and safety issues in
      pharmaceutical development to their association with a number of chronic
      diseases. The aggregated, often amyloid, protein state is often considered to be
      more thermodynamically and kinetically stable than (partially) unfolded or folded
      monomers except under highly denaturing conditions. However, evolution of the
      structure and stability of aggregated states has received much less attention.
      Here it is shown that under mildly-denaturing conditions (elevated temperature or
      [urea]), where the native monomer (N) is slightly favored compared to the
      unfolded state (U), alpha-chymotrypsinogen A (aCgn) non-native aggregates undergo
      a structural relaxation or annealing process to reach even more stable states.
      The annealed aggregates are more resistant to dissociation than aggregates that
      do not undergo this relaxation process. Aggregates without annealing dissociate
      via linear chain depolymerization, and annealing is accelerated under conditions
      that promote slow dissociation (partially denaturing conditions). This is
      consistent with a free energy landscape with multiple barriers and local minima
      that allows for a kinetic competition between aggregate dissociation and
      structural relaxation to more stable aggregate states. This highlights added
      complexities for protein refolding or aggregate dissociation processes, and may
      explain why it is often difficult to completely recover monomeric protein from
      aggregates.

PMID- 24122553
TI  - The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic
      reticulum stress.
AB  - Human DNAJC12 is a J domain-containing protein whose regulation, subcellular
      localization, and function are currently unknown. We show here that the abundance
      of DNAJC12 in human LNCaP prostate cancer cells is upregulated by the stress
      inducing drug A23187 and by the stressregulated transcription factor
      AIbZIP/CREB3L4. The DNAJC12 gene encodes two isoforms, only one of which (isoform
      a) is expressed in these cells. Immunofluorescence studies showed that a
      recombinant DNAJC12 protein is diffusely distributed in the cytoplasm. To
      identify substrates of DNAJC12, we used an immunoaffinity-mass spectrometry
      approach in cells that express epitope-tagged DNAJC12. The list of potential
      DNAJC12-binding proteins that were identified in this screen includes several
      nucleotide-binding proteins. The most frequently identified partner of DNAJC12 in
      unstressed cells was Hsc70, a cognate Hsp70 chaperone, whereas in stressed cells,
      the ER chaperone BiP was frequently associated with DNAJC12. Immunoprecipitation
      experiments confirmed that the endogenous DNAJC12 and Hsc70 proteins interact in
      LNCaP cells. These results clarify the role of DNAJC12 in the regulation of Hsp70
      function.

PMID- 24122555
TI  - A Kalman filter approach for denoising and deblurring 3-D microscopy images.
AB  - This paper proposes a new method for removing noise and blurring from 3D
      microscopy images. The main contribution is the definition of a space-variant
      generating model of a 3-D signal, which is capable to stochastically describe a
      wide class of 3-D images. Unlike other approaches, the space-variant structure
      allows the model to consider the information on edge locations, if available. A
      suitable description of the image acquisition process, including blurring and
      noise, is then associated to the model. A state-space realization is finally
      derived, which is amenable to the application of standard Kalman filter as an
      image restoration algorithm. The so obtained method is able to remove, at each
      spatial step, both blur and noise, via a linear minimum variance recursive one
      shot procedure, which does not require the simultaneous processing of the whole
      image. Numerical results on synthetic and real microscopy images confirm the
      merit of the approach.

PMID- 24122554
TI  - Alcohol stress, membranes, and chaperones.
AB  - Ethanol, which affects all body organs, exerts a number of cytotoxic effects,
      most of them independent of cell type. Ethanol treatment leads to increased
      membrane fluidity and to changes in membrane protein composition. It can also
      interact directly with membrane proteins, causing conformational changes and
      thereby influencing their function. The cytotoxic action may include an increased
      level of oxidative stress. Heat shock protein molecular chaperones are
      ubiquitously expressed evolutionarily conserved proteins which serve as critical
      regulators of cellular homeostasis. Heat shock proteins can be induced by various
      forms of stresses such as elevated temperature, alcohol treatment, or ischemia,
      and they are also upregulated in certain pathological conditions. As heat shock
      and ethanol stress provoke similar responses, it is likely that heat shock
      protein activation also has a role in the protection of membranes and other
      cellular components during alcohol stress.

PMID- 24122557
TI  - Combined effects of food deprivation and food frequency on the amount and
      temporal distribution of schedule-induced drinking.
AB  - Under intermittent food schedules animals develop temporally organized behaviors
      throughout interfood intervals, with behaviors early in the intervals (interim)
      normally occurring in excess. Schedule-induced drinking (a prototype of interim,
      adjunctive behavior) is related to food deprivation and food frequency. This
      study investigated the interactions that resulted from combining different food
      deprivation levels (70%, 80% or 90% free-feeding weights) with different food
      occurrence frequencies (15-, 30- or 60-s interfood intervals) in a within
      subjects design. Increases in food deprivation and food frequency generally led
      to increased licking, with greater differences due to food deprivation as
      interfood intervals became shorter. Distributions of licking were modestly
      shifted to later in the interfood interval as interfood intervals lengthened, a
      result that was most marked under 90% food deprivation, which also resulted in
      flatter distributions. It would therefore appear that food deprivation modulates
      the licking rate and the distribution of licking in different ways. Effects of
      food deprivation and food frequency are adequately explained by a theory of
      adjunctive behavior based on delayed food reinforcement, in contrast to
      alternative hypotheses. 

PMID- 24122556
TI  - Radar chart array analysis to visualize effects of formulation variables on IgG1
      particle formation as measured by multiple analytical techniques.
AB  - This study presents a novel method to visualize protein aggregate and particle
      formation data to rapidly evaluate the effect of solution and stress conditions
      on the physical stability of an immunoglobulin G (IgG) 1 monoclonal antibody
      (mAb). Radar chart arrays were designed so that hundreds of microflow digital
      imaging (MFI) solution measurements, evaluating different mAb formulations under
      varying stresses, could be presented in a single figure with minimal loss of data
      resolution. These MFI radar charts show measured changes in subvisible particle
      number, size, and morphology distribution as a change in the shape of polygons.
      Radar charts were also created to visualize mAb aggregate and particle formation
      across a wide size range by combining data sets from size-exclusion
      chromatography, Archimedes resonant mass measurements, and MFI. We found that the
      environmental/mechanical stress condition (e.g., heat vs. agitation) was the most
      important factor in influencing the particle size and morphology distribution
      with this IgG1 mAb. Additionally, the presence of NaCl exhibited a pH and stress
      dependent behavior resulting in promotion or inhibition mAb particle formation.
      This data visualization technique provides a comprehensive analysis of the
      aggregation tendencies of this IgG1 mAb in different formulations with varying
      stresses as measured by different analytical techniques.

PMID- 24122558
TI  - The rediscovery of H. pylori bacteria in the gastric mucosa by Robin Warren, and
      implications of this finding for human biology and disease.

PMID- 24122559
TI  - Prediction of the postoperative prognosis of intrahepatic cholangiocarcinoma
      (ICC): importance of preoperatively- determined anatomic invasion level and
      number of tumors.
AB  - BACKGROUND: Preoperative prediction of the prognosis of patients with
      intrahepatic cholangiocarcinoma (ICC) following surgical treatment remains quite
      difficult and controversial. We attempted to identify the preoperative and
      postoperative predictors of the overall survival rates inpatients with ICC in
      order to clarify the appropriate indications for surgical resection of ICC.
      PATIENTS AND METHODS: We retrospectively investigated the clinicopathological
      features of ICC and outcome of surgical resection in 111 consecutive patients who
      underwent surgical treatment at our hospital between 1980 and March 2012. Both
      preoperative factors and operatively confirmed factors were evaluated as
      potential risk factors for determination of the post-surgical prognosis. RESULTS:
      Curative resection (R0) was performed in 72 patients (64.9 %). The 1- and 3-year
      overall survival rates were 85.0 and 59.7 % in the R0 group. Two preoperative
      factors [hilar invasion as recognized by computed tomography(HR 3.16, P = 0.020)
      and multiple intrahepatic tumors (HR 7.09, P = 0.0002)] and two operatively
      confirmed factors [multiple intrahepatic tumors (HR 9.17,P = 0.0009) and lymph
      node metastasis as confirmed by final histology (HR 6.41, P = 0.003)] were
      identified as significant risk factors adversely influencing the overall survival
      rate after surgery. Furthermore, solitary, small(?5 cm) and peripheral ICCs were
      associated with a very low probability of lymph node metastasis. CONCLUSIONS:
      Preoperatively diagnosed hilar invasion,multiple intrahepatic tumors and
      histologically confirmed lymph node metastasis were the main determinants of an
      adverse postoperative prognosis in patients with ICC.Lymph node dissection could
      be omitted for patients with solitary, small and peripheral ICCs.

PMID- 24122560
TI  - Complete genome sequences of porcine reproductive and respiratory syndrome
      viruses: perspectives on their temporal and spatial dynamics.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) has been investigated
      extensively at the molecular level. Nevertheless, genome wide study on the
      temporal and spatial dynamics of the virus is non-existed. To explore this topic,
      we determined complete coding genome sequences for four PRRSV isolates and
      analyzed them together with 122 global published ones using the Bayesian
      coalescent approach as well as Bayesian inferences and maximum likelihood
      methods. All EU-type viruses belonged to one of two groups or were unclassified
      (5 isolates), and all NA-type isolates were divided into one of three major
      groups or were unclassified (1 isolate). Here, there was no apparent association
      between temporal or geographic origin and heterogeneity of global PRRSVs. Of the
      eight ORFs, ORF1a showed the most powerful evolutionary signal. Our findings also
      indicated that the PRRS virus evolved at a rate of 1.98 * 10-3
      substitutions/site/year, and the most recent common ancestor of the virus existed
      786.4 years ago. Here, EU-type viruses segregated 115.7 years ago, while NA-type
      isolates diverged 179.8 years before the present. In addition, our reconstruction
      of the effective population size depicted five phases of epidemic growth: an
      initial constant, followed sequentially by slow decrease, slight increase, sharp
      decline, and then a rapid expansion approaching the present.

PMID- 24122561
TI  - Interactive rehabilitation system for improvement of balance therapies in people
      with cerebral palsy.
AB  - The present study covers a new experimental system, designed to improve the
      balance and postural control of adults with cerebral palsy. This system is based
      on a serious game for balance rehabilitation therapy, designed using the
      prototype development paradigm and features for rehabilitation with serious
      games: feedback, adaptability, motivational elements, and monitoring. In
      addition, the employed interaction technology is based on computer vision because
      motor rehabilitation consists of body movements that can be recorded, and because
      vision capture technology is noninvasive and can be used for clients who have
      difficulties in holding physical devices. Previous research has indicated that
      serious games help to motivate clients in therapy sessions; however, there
      remains a paucity of clinical evidence involving functionality. We rigorously
      evaluated the effects of physiotherapy treatment on balance and gait function of
      adult subjects with cerebral palsy undergoing our experimental system. A 24-week
      physiotherapy intervention program was conducted with nine adults from a cerebral
      palsy center who exercised weekly in 20-min sessions. Findings demonstrated a
      significant increase in balance and gait function scores resulting in indicators
      of greater independence for our participating adults. Scores improved from 16 to
      21 points in a scale of 28, according to the Tinetti Scale for risk of falls,
      moving from high fall risk to moderate fall risk. Our promising results indicate
      that our experimental system is feasible for balance rehabilitation therapy.

PMID- 24122562
TI  - Robot assisted physiotherapy to support rehabilitation of facial paralysis.
AB  - We have been developing the Robot Mask with shape memory alloy based actuators
      that follows an approach of manipulating the skin through a minimally obtrusive
      wires, transparent strips and tapes based pulling mechanism to enhance the
      expressiveness of the face. For achieving natural looking facial expressions by
      taking the advantage of specific characteristics of the skin, the Robot Mask
      follows a human anatomy based criteria in selecting these manipulation points and
      directions. In this paper, we describe a case study of using the Robot Mask to
      assist physiotherapy of a hemifacial paralyzed patient. The significant
      differences in shape and size of the human head between different individuals
      demands proper customizations of the Robot Mask. This paper briefly describes the
      adjusting and customizing stages employed from the design level to the
      implementation level of the Robot Mask. We will also introduce a depth image
      sensor data based analysis, which can remotely evaluate dynamic characteristics
      of facial expressions in a continuous manner. We then investigate the
      effectiveness of the Robot Mask by analyzing the range sensor data. From the case
      study, we found that the Robot Mask could automate the physiotherapy tasks of
      rehabilitation of facial paralysis. We also verify that, while providing quick
      responses, the Robot Mask can reduce the asymmetry of a smiling face and
      manipulate the facial skin to formations similar to natural facial expressions. 

PMID- 24122563
TI  - Effect of early and late rehabilitation onset in a chronic rat model of ischemic
      stroke- assessment of motor cortex signaling and gait functionality over time.
AB  - The aim of the present study was to investigate the effects of ischemic stroke
      and onset of subsequent rehabilitation of gait function in rats. Nine male
      Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC)
      electrode array. An ischemic stroke was induced within the hindlimb area of the
      left motor cortex. The rehabilitation consisted of a repetitive training paradigm
      over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven,
      ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests,
      treadmill walking tests, and beam walking tests. Results revealed an expansion of
      the hindlimb representation within the motor cortex area and an increased amount
      of cortical firing rate modulation for the "Early-onset" group but not for the
      "Late-onset" group. Kinematic data revealed a significant change for both
      intervention groups. However, this difference was larger for the "Early-onset"
      group. Results from the beam walking test showed functional performance deficits
      following stroke which returned to pre-stroke level after the rehabilitative
      training. The results from the present study indicate the existence of a critical
      time period following stroke where onset of rehabilitative training may be more
      effective and related to a higher degree of true recovery. 

PMID- 24122564
TI  - High-density intracortical microelectrode arrays with multiple metallization
      layers for fine-resolution neuromonitoring and neurostimulation.
AB  - Intracortical microelectrodes play a prominent role in the operation of neural
      interfacing systems. They provide an interface for recording neural activities
      and modulating their behavior through electric stimulation. The performance of
      such systems is thus directly meliorated by advances in electrode technology. We
      present a new architecture for intracortical electrodes designed to increase the
      number of recording/stimulation channels for a given set of shank dimensions. The
      architecture was implemented on silicon using microfabrication process and
      fabricated 3-mm-long electrode shanks with six relatively large (110 MUm *110
      MUm) pads in each shank for electrographic signal recording to detect important
      precursors with potential clinical relevance and electrical stimulation to
      correct neural behavior with low-power dissipation in an implantable device.
      Moreover, an electrode mechanical design was developed to increase its stiffness
      and reduce shank deflection to improve spatial accuracy during an electrode
      implantation. Furthermore, the pads were post-processed using pulsated low
      current electroplating and reduced their impedances by ~ 30 times compared to the
      traditionally fabricated pads. The paper also presents microfabrication process,
      electrodes characterization, comparison to the commercial equivalents, and in
      vitro and in vivo validations.

PMID- 24122565
TI  - L1-regularized Multiway canonical correlation analysis for SSVEP-based BCI.
AB  - Canonical correlation analysis (CCA) between recorded electroencephalogram (EEG)
      and designed reference signals of sine-cosine waves usually works well for steady
      state visual evoked potential (SSVEP) recognition in brain-computer interface
      (BCI) application. However, using the reference signals of sine- cosine waves
      without subject-specific and inter-trial information can hardly give the optimal
      recognition accuracy, due to possible overfitting, especially within a short time
      window length. This paper introduces an L1-regularized multiway canonical
      correlation analysis (L1-MCCA) for reference signal optimization to improve the
      SSVEP recognition performance further. A multiway extension of the CCA, called
      MCCA, is first presented, in which collaborative CCAs are exploited to optimize
      the reference signals in correlation analysis for SSVEP recognition alternatingly
      from the channel-way and trial-way arrays of constructed EEG tensor. L1
      regularization is subsequently imposed on the trial-way array optimization in the
      MCCA, and hence results in the more powerful L1-MCCA with function of effective
      trial selection. Both the proposed MCCA and L1-MCCA methods are validated for
      SSVEP recognition with EEG data from 10 healthy subjects, and compared to the
      ordinary CCA without reference signal optimization. Experimental results show
      that the MCCA significantly outperforms the CCA for SSVEP recognition. The L1
      MCCA further improves the recognition accuracy which is significantly higher than
      that of the MCCA. 

PMID- 24122566
TI  - User training for pattern recognition-based myoelectric prostheses: improving
      phantom limb movement consistency and distinguishability.
AB  - We assessed the ability of four transradial amputees to control a virtual
      prosthesis capable of nine classes of movement both before and after a two-week
      training period. Subjects attended eight one-on-one training sessions that
      focused on improving the consistency and distinguishability of their hand and
      wrist movements using visual biofeedback from a virtual prosthesis. The virtual
      environment facilitated the precise quantification of three prosthesis control
      measures. During a final evaluation, the subject population saw an average
      increase in movement completion percentage from 70.8% to 99.0%, an average
      improvement in normalized movement completion time from 1.47 to 1.13, and an
      average increase in movement classifier accuracy from 77.5% to 94.4% (p<0.001).
      Additionally, all four subjects were reevaluated after eight elapsed hours
      without retraining the classifier, and all subjects demonstrated minimal
      decreases in performance. Our analysis of the underlying sources of improvement
      for each subject examined the sizes and separation of high-dimensional data
      clusters and revealed that each subject formed a unique and effective strategy
      for improving the consistency and/or distinguishability of his or her phantom
      limb movements. This is the first longitudinal study designed to examine the
      effects of user training in the implementation of pattern recognition-based
      myoelectric prostheses. 

PMID- 24122567
TI  - Initial Skill Acquisition of Handrim Wheelchair Propulsion: A New Perspective.
AB  - To gain insight into cyclic motor learning processes, hand rim wheelchair
      propulsion is a suitable cyclic task, to be learned during early rehabilitation
      and novel to almost every individual. To propel in an energy efficient manner,
      wheelchair users must learn to control bimanually applied forces onto the rims,
      preserving both speed and direction of locomotion. The purpose of this study was
      to evaluate mechanical efficiency and propulsion technique during the initial
      stage of motor learning. Therefore, 70 naive able-bodied men received 12-min
      uninstructed wheelchair practice, consisting of three 4-min blocks separated by 2
      min rest. Practice was performed on a motor-driven treadmill at a fixed belt
      speed and constant power output relative to body mass. Energy consumption and the
      kinetics of propulsion technique were continuously measured. Participants
      significantly increased their mechanical efficiency and changed their propulsion
      technique from a high frequency mode with a lot of negative work to a longer
      slower movement pattern with less power losses. Furthermore a multi-level model
      showed propulsion technique to relate to mechanical efficiency. Finally improvers
      and non-improvers were identified. The non-improving group was already more
      efficient and had a better propulsion technique in the first block of practice
      (i.e., the fourth minute). These findings link propulsion technique to mechanical
      efficiency, support the importance of a correct propulsion technique for
      wheelchair users and show motor learning differences. 

PMID- 24122568
TI  - Dynamic Optimization of FES and Orthosis-Based Walking Using Simple Models.
AB  - Computation of an analytical control solution for functional electrical
      stimulation (FES) and orthosis-based walking is a daunting task due to the
      inherent nonlinear structure of the human muscle and walking dynamics.
      Furthermore, since muscle fatigue and available muscle force are major limiting
      issues, we explored the domains of numerical optimal control methods to address
      these issues. We first focused on the development of simple models to represent
      walking movement. These models account for walking produced via a limited number
      of activated muscles using FES along with a novel orthosis, and an assistive
      device such as a walker. Using dynamic optimization, the lower limb joint angle
      trajectories and control inputs were computed by minimizing the cost function
      comprising muscle stimulation variables and forces required to push a walker.
      Computer simulations for optimizations were performed across a range of step
      lengths to find the optimal step length (minimum cost per distance). Then, the
      optimal steady-state initial angular velocity (for optimal step length) was
      computed from a range of angular velocities of the lower-limb segments. We found
      considerable differences between able-bodied walking trajectories and the optimal
      walking trajectories for FES and orthosis-based walking. Based on this computer
      simulation study, we recommend that instead of arbitrary selection of stimulation
      profiles or gait parameters, dynamic optimization can be utilized to compute gait
      parameters such as step length, steady state velocity, and joint angle
      trajectories in future clinical implementation of FES and orthosis-based walking.

PMID- 24122569
TI  - Particle Swarm Optimization Applied to EEG Source Localization of Somatosensory
      Evoked Potentials.
AB  - One of the most important steps in presurgical diagnosis of medically intractable
      epilepsy is to find the precise location of the epileptogenic foci.
      Electroencephalography (EEG) is a noninvasive tool commonly used at epilepsy
      surgery centers for presurgical diagnosis. In this paper, a modified particle
      swarm optimization (MPSO) method is used to solve the EEG source localization
      problem. The method is applied to noninvasive EEG recording of somatosensory
      evoked potentials (SEPs) for a healthy subject. A 1 mm hexahedra finite element
      volume conductor model of the subject's head was generated using T1-weighted
      magnetic resonance imaging data. Special consideration was made to accurately
      model the skull and cerebrospinal fluid. An exhaustive search pattern and the
      MPSO method were then applied to the peak of the averaged SEP data and both
      identified the same region of the somatosensory cortex as the location of the SEP
      source. A clinical expert independently identified the expected source location,
      further corroborating the source analysis methods. The MPSO converged to the
      global minima with significantly lower computational complexity compared to the
      exhaustive search method that required almost 3700 times more evaluations. 

PMID- 24122570
TI  - Seizure prediction using spike rate of intracranial EEG.
AB  - Reliable prediction of forthcoming seizures will be a milestone in epilepsy
      research. A method capable of timely predicting the occurrence of seizures could
      significantly improve the quality of life for epilepsy patients and open new
      therapeutic approaches. Seizures are usually characterized by generalized spike
      wave discharges. With the advent of seizures, the variation of spike rate (SR)
      will have different manifestations. In this study, a seizure prediction approach
      based on spike rate is proposed and evaluated. Firstly, a low-pass filter is
      applied to remove the high frequency artifacts in electroencephalogram (EEG).
      Then, the morphology filter is used to detect spikes and compute SR, and SR is
      smoothed with an average filter. Finally, the performance of smoothed SR (SRm) in
      EEG during interictal, preictal, and ictal periods is analyzed and employed as an
      index for seizure prediction. Experiments with long-term intracranial EEGs of 21
      patients show that the proposed seizure prediction approach achieves a
      sensitivity of 75.8% with an average false prediction rate of 0.09/h. The low
      computational complexity of the proposed approach enables its possibility of
      applications in an implantable device for epilepsy therapy. 

PMID- 24122571
TI  - Design and Validation of the Ankle Mimicking Prosthetic (AMP-) Foot 2.0.
AB  - Transtibial (TT) amputations, or below-knee amputations, are among the most
      frequently performed major limb removals. To replace the missing limb, numerous
      prosthetic devices were developed. A study of the state-of-the-art in TT
      prostheses shows that none of the commercially available devices are capable of
      mimicking an able-bodied ankle-foot complex. Still on a research level, some
      powered prosthetic devices have the potential to improve amputee walking
      experience, but still need heavy and bulky actuators to provide the necessary
      power of propulsion. With the AMP-Foot 2.0, the authors propose a new concept for
      an energy efficient, powered transtibial prosthesis. Its design enables the use
      of a low power actuator which stores energy in springs during the complete stance
      phase that can be released at push-off. Thanks to this, the size and weight of
      the actuator can be decreased considerably while the ankle still provides the
      full power necessary for forward propulsion. A prototype of the AMP-Foot 2.0 has
      been built and experiments with a transfemural amputee were conducted. The
      captured data is presented and analyzed throughout this paper. 

PMID- 24122572
TI  - Validation of a method for real time foot position and orientation tracking with
      Microsoft Kinect technology for use in virtual reality and treadmill based gait
      training programs.
AB  - The use of virtual reality for the provision of motor-cognitive gait training has
      been shown to be effective for a variety of patient populations. The interaction
      between the user and the virtual environment is achieved by tracking the motion
      of the body parts and replicating it in the virtual environment in real time. In
      this paper, we present the validation of a novel method for tracking foot
      position and orientation in real time, based on the Microsoft Kinect technology,
      to be used for gait training combined with virtual reality. The validation of the
      motion tracking method was performed by comparing the tracking performance of the
      new system against a stereo-photogrammetric system used as gold standard. Foot
      position errors were in the order of a few millimeters (average RMSD from 4.9 to
      12.1 mm in the medio-lateral and vertical directions, from 19.4 to 26.5 mm in the
      anterior-posterior direction); the foot orientation errors were also small
      (average %RMSD from 5.6% to 8.8% in the medio-lateral and vertical directions,
      from 15.5% to 18.6% in the anterior-posterior direction). The results suggest
      that the proposed method can be effectively used to track feet motion in virtual
      reality and treadmill-based gait training programs. 

PMID- 24122573
TI  - Multi-muscle FES force control of the human arm for arbitrary goals.
AB  - We present a method for controlling a neuroprosthesis for a paralyzed human arm
      using functional electrical stimulation (FES) and characterize the errors of the
      controller. The subject has surgically implanted electrodes for stimulating
      muscles in her shoulder and arm. Using input/output data, a model mapping muscle
      stimulations to isometric endpoint forces measured at the subject's hand was
      identified. We inverted the model of this redundant and coupled multiple-input
      multiple-output system by minimizing muscle activations and used this inverse for
      feedforward control. The magnitude of the total root mean square error over a
      grid in the volume of achievable isometric endpoint force targets was 11% of the
      total range of achievable forces. Major sources of error were random error due to
      trial-to-trial variability and model bias due to nonstationary system properties.
      Because the muscles working collectively are the actuators of the skeletal
      system, the quantification of errors in force control guides designs of motion
      controllers for multi-joint, multi-muscle FES systems that can achieve arbitrary
      goals. 

PMID- 24122574
TI  - Electromyogram bandwidth requirements when the signal is whitened.
AB  - Whitening the surface electromyogram (EMG) improves EMG amplitude (EMGsigma) and
      EMG-torque estimation. Laboratory studies utilizing contraction levels up to
      maximum voluntary contraction (MVC) show that whitening is useful over a
      frequency band extending to 1000-2000 Hz. However, EMG electrode systems with
      such wide bandwidth are uncommon, particularly in real-time applications; and
      these contraction levels are also not common. Thus, we studied the influence of
      the frequency band over which whitening was performed versus the resulting
      performance. Low-level, torque-varying contractions (average torque level of
      18.5% flexion MVC) of the elbow were contrasted with medium-level 50% MVC
      constant-torque contractions. For each, the maximum whitening bandwidth was
      varied between 30-2000 Hz. The low-level contractions (which incorporate the
      contraction range of most daily tasks) showed that performance utilizing
      frequencies out to 400-500 Hz was not statistically different than results out to
      the full available frequency (2000 Hz). For the medium-level (50% MVC)
      contractions, frequencies out to 800-900 Hz were statistically equivalent to the
      full bandwidth. These results suggest that conventional electrodes with a typical
      passband of ~ 500 Hz are appropriate when whitening data from contraction levels
      typically experienced in many applications. Wider bandwidths may be advantageous
      for strenuous activities.

PMID- 24122575
TI  - Tobacco dependence treatment: influence of training experiences on clinical
      activities among otolaryngologists.
AB  - OBJECTIVES/HYPOTHESIS: Although one in five U.S. adults continue to smoke,
      healthcare providers often fail to provide basic, effective interventions. This
      is particularly true for physician specialists. This study sought to investigate
      perceived role, self-efficacy, practice behaviors, and attitudes among
      otolaryngologists as they relate to the delivery of tobacco treatment services.
      STUDY DESIGN: This study involved a single administration of a survey
      questionnaire to current members of the American Academy of Otolaryngology Head
      and Neck Surgery (AAO-HNS). METHODS: A questionnaire was mailed up to three times
      to active members. RESULTS: Survey response rate was 39% (N = 2127). Based on an
      evaluation of treatment factors categorized according to the National Cancer
      Institute's 5A's approach, trained providers generally rated themselves
      consistently higher than untrained providers across areas of clinical activity.
      Minimal differences were noted for Ask and Advise, moderate for Assess, and the
      greatest for Assist and Arrange. Trained providers also indicated more positive
      attitudes towards treatment. CONCLUSIONS: While the level of performance was
      reasonable for otolaryngologists relative to other specialists in the published
      literature, overall tobacco treatment activity remains unacceptably low. This
      study suggests the positive impact of training and the potential value of making
      such experiences widely available.

PMID- 24122576
TI  - Microwave coagulation for liver metastases.
AB  - BACKGROUND: Primary liver cancer and liver metastases from colorectal carcinoma
      are the two most common malignant tumours to affect the liver. The liver is
      second only to the lymph nodes as the most common site for metastatic disease.
      More than half of patients with metastatic liver disease will die from metastatic
      complications. Microwave coagulation involves placing an electrode into a lesion
      under ultrasound or computed tomography guidance. The microwave coagulator
      generates and transmits microwave energy to the electrode. Coagulative necrosis
      causes cellular death and destroys tissue in the treatment area, resulting in
      reduction of tumour size. OBJECTIVES: To study the beneficial and harmful effects
      of microwave coagulation compared with no intervention, other ablation methods,
      or systemic treatments in patients with liver metastases. SEARCH METHODS: We
      searched the Cochrane Hepato-Biliary Group Controlled Trials Register, The
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to
      December 2012. SELECTION CRITERIA: We included all randomised clinical trials
      assessing beneficial and harmful effects of microwave coagulation and its
      comparators, irrespective of the location of the primary tumour. DATA COLLECTION
      AND ANALYSIS: We extracted relevant information on participant characteristics,
      interventions, and study outcomes and data on outcome measures for our review, as
      well as information on design and methodology of the studies. Bias risk
      assessment of trials, determination of whether they fulfilled the inclusion
      criteria, and data extraction from retrieved for final evaluation trials were
      done by one review author and were checked by a second review author. MAIN
      RESULTS: One randomised clinical trial fulfilled the inclusion criteria of the
      review. Forty participants with multiple liver metastases of colorectal cancer
      and no evidence of extrahepatic disease were randomly assigned. Thirty of these
      participants (14 females and 16 males) were included in the analysis: 14
      participants received microwave coagulation and 16 underwent conventional surgery
      (hepatectomy or liver resection). The diagnosis of colorectal cancer (Stage IB to
      IIIC; tumour (T)2 node (N)0 to T3N2) and liver metastases was confirmed by
      histological assessment. Mean participant age was 61 years. The tumours were
      resectable. The risk of bias in the trial was judged to be high.Participants were
      followed for three years. Mortality at the last follow-up was 64% (9/14) in the
      microwave group and 75% (12/16) in the conventional surgery group (risk ratio
      (RR) 0.86; 95% confidence interval (CI) 0.53 to 1.39), that is, no significant
      difference was observed. In the microwave coagulation group, 71%, 57%, and 14%
      survived 1, 2, and 3 years, and in the conventional surgery group, the
      percentages were 69%, 56%, and 23%. The hazard ratio calculated using the Parmar
      method was 0.91 (0.39 to 2.15).Mean survival time was 27 months in the microwave
      group and 25 months in the conventional surgery group, and the mean disease-free
      interval was 11.3 months in the microwave group and 13.3 months in the
      hepatectomy group. Differences for both outcomes were not statistically
      significant. Reported frequency of adverse events was similar between the
      microwave coagulation and conventional surgery groups, except for the required
      blood transfusion, which was more common in the conventional surgery group. No
      intervention-related mortality was observed. After treatment, the
      carcinoembryonic antigen level decreased significantly in both groups. AUTHORS'
      CONCLUSIONS: On the basis of one randomised clinical trial, which did not
      describe allocation concealment or blinding, and which excluded from analysis 25%
      of participants after random assignment, evidence is insufficient to show whether
      microwave coagulation brings any significant benefit in terms of survival or
      recurrence compared with conventional surgery for participants with liver
      metastases from colorectal cancer. The number of adverse events, except for the
      requirement for blood transfusion, which was more common in the liver resection
      group, was similar in both groups. At present, microwave therapy cannot be
      recommended outside randomised clinical trials.

PMID- 24122577
TI  - The psychosocial impact of dental aesthetics questionnaire--translation and cross
      cultural validation in Croatia.
AB  - PURPOSE: To perform a translation and validation of the psychosocial impact of
      dental aesthetics questionnaire (PIDAQ) in the Croatian cultural context.
      METHODS: A total of 262 subjects (34 % males) aged 18-30 years (mean age 22.7 +/-
      2.6) were included. The questionnaire included the PIDAQ, a self-assessment of
      satisfaction with dental aesthetics, a self-perceived dental treatment need
      assessment, self-reported malocclusion, an aesthetic component of index of
      orthodontic treatment need (IOTN AC) and an oral health impact profile (OHIP-14
      CRO). The subjects' orthodontic treatment needs were assessed by a dentist using
      the dental health and aesthetic component of the IOTN. The internal consistency,
      test-retest reliability, validity and responsiveness were assessed. Little's
      Irregularity index was used to correlate the amount of resolution of dental
      crowding by orthodontic treatment with the change in PIDAQ domains. RESULTS: The
      domains of the Croatian version of the PIDAQ showed satisfactory internal
      consistency (alpha ranging from 0.79 to 0.95) and high test-retest reliability (r
      > 0.85). The significant association between the PIDAQ domains and self-reported
      satisfaction with teeth appearance, IOTN AC and OHIP-14 CRO (p < 0.001) confirmed
      the convergent validity. The domains were able to detect differences in the
      subjects' psychosocial impact related to orthodontic treatment that improved
      dental aesthetics in responsiveness testing (p < 0.001). CONCLUSION: The Croatian
      version of the PIDAQ demonstrated good psychometric properties, similar to those
      of the original.

PMID- 24122578
TI  - "Close-knit" defines a healthy Native American Indian family.
AB  - In the United States, the most significant health disparities occur among members
      of the American Indian and Alaskan Native populations. Because their health
      beliefs, values, and cultural practices are learned within a family system, this
      study used a focused ethnography to explore American Indians' perceptions of a
      healthy family. Seventeen interviews were performed with 21 adults residing on a
      reservation on the Northern Plains of the United States. Participant observation
      was conducted during 100 hr of fieldwork. All informants identified a healthy
      family as being "close-knit," indicating that the major defining feature of these
      families is the degree of connectedness among members, immediate and extended. In
      this paper, we present adult tribal members' descriptions of a healthy family. It
      is evident that culturally appropriate programs, which consider American Indians'
      values/beliefs and build on community assets, are urgently needed to reduce
      health disparities. 

PMID- 24122579
TI  - Invisible hands: the role of highly involved families in long-term residential
      care.
AB  - Care work by family and friends is recognized as a cornerstone of community-based
      care for older adults; however, the role of families in institutional-based care
      work has been less well understood and researched. Drawing on findings from a
      critical ethnographic study, this article aims to examine the unique role of
      highly involved family members within long-term residential care. The study took
      place between October 2006 and April 2008 in two facilities in British Columbia,
      Canada. A purposive sample of 11 highly involved family members participated in
      in-depth interviews and participant observations. The main themes were "Hands
      On," "Hands-Off," "Surveillance," and "Interlopers." These themes illuminate the
      ways in which highly involved family members engaged in care work, including how
      they positioned themselves and were positioned by staff and administrators.
      Implications of the study focus on the need to include families in philosophies
      of care and policies that shape care work in long-term residential care. 

PMID- 24122580
TI  - Being the parent of a ventilator-assisted child: perceptions of the family-health
      care provider relationship when care is offered in the family home.
AB  - The number of medically fragile children cared for at home is increasing;
      however, there are few studies about the professional support these families
      receive in their homes. The aim of the study was to understand the meanings that
      parents had about the support they received from health care professionals who
      offered care for their ventilator-assisted child in the family home. A
      phenomenological-hermeneutic method was used. Data included the narratives of
      five mother-father couples living in Sweden who were receiving professional
      support for their ventilator-assisted child. The findings indicate that receiving
      professional support meant being at risk of and/or exposed to the exercise of
      control over family privacy. The professional support system in the families'
      homes worked more by chance than by competent and sensible planning. In good
      cases, caring encounters were characterized by a mutual relationship where
      various occupational groups were embraced as a part of family life. The findings
      are discussed in light of compassionate care, exercise of power, and the
      importance of holistic educational programs. 

PMID- 24122581
TI  - Aortoesophageal fistula and coarctation of the aorta in a 15-year-old child.
AB  - Delayed presentation of coarctation of the aorta can be associated with severe
      complications. A challenging case of aortoenteric fistula secondary to an
      aneurysm from coartation of the aorta presented with massive gastrointestinal
      hemorrhage. The clinical management of this patient and a review of the
      literature are presented. 

PMID- 24122583
TI  - Current status of optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a novel imaging technology based on low
      coherence interferometry that use near-infrared light in real-time, and allows
      cross-sectional in-situ visualization of the vessel wall at the microscopic
      level. OCT provides 10-fold higher resolution than intravascular ultrasound which
      is currently the most used modality for intra-coronary imaging. OCT offers the
      obvious advantages when characterizing precise plaque microstructure and
      distinguishing various type of plaques. OCT is also being assessed for its
      potential role in the understanding of neointimal coverage, vascular healing and
      the progression of atherosclerosis in coronary vasculature after stenting on the
      micron scale. These unique capabilities could be helpful in guiding coronary
      management and interventions. Recent improvement in next generation OCT
      technology, such as frequency-domain OCT, will allow for a simple imaging
      procedure, providing more useful information and complementing other modalities
      on both clinical and research applications for the cardiologists. 

PMID- 24122582
TI  - PI3K/AKT pathway activation in bladder carcinogenesis.
AB  - The PI3K/AKT pathway is considered to play a major role in bladder
      carcinogenesis, but its relationships with other molecular alterations observed
      in bladder cancer remain unknown. We investigated PI3K/AKT pathway activation in
      a series of human bladder urothelial carcinomas (UC) according to PTEN
      expression, PTEN deletions and FGFR3, PIK3CA, KRAS, HRAS, NRAS and TP53 gene
      mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta
      n = 25, T1 n = 34, T2-T3-T4 n = 70). Expression of phospho-AKT (pAKT), phospho-S6
      Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN
      was evaluated by reverse phase protein Array. Expression of miR-21, miR-19a and
      miR-222, known to regulate PTEN expression, was also evaluated. pAKT expression
      levels were higher in tumors than in normal urothelium (p < 0.01), regardless of
      stage and showed a weak and positive correlation with pS6 (Spearman coefficient
      RS = 0.26; p = 0.002). No association was observed between pAKT or pS6 expression
      and the gene mutations studied. PTEN expression was decreased in PTEN-deleted
      tumors, and in T1 (p = 0.0089) and T2-T3-T4 (p < 0.001) tumors compared to Ta
      tumors; it was also negatively correlated with miR-19a (RS = -0.50; p = 0.0088)
      and miR-222 (RS = -0.48; p = 0.0132), but not miR-21 (RS = -0.27; p = 0.18)
      expression. pAKT and PTEN expressions were not negatively correlated, and, on the
      opposite, a positive and moderate correlation was observed in Ta (RS = 0.54; p =
      0.0056) and T1 (RS = 0.56; p = 0.0006) tumors. Our study suggests that PI3K/AKT
      pathway activation occurs in the entire spectrum of bladder UC regardless of
      stage or known most frequent molecular alterations, and independently of low PTEN
      expression. 

PMID- 24122584
TI  - Comparison of neointimal morphology of in-stent restenosis with sirolimus-eluting
      stents versus bare metal stents: virtual histology-intravascular ultrasound
      analysis.
AB  - Sirolimus-eluting stents (SES) have reduced the incidence of restenosis and
      target lesion revascularization compared to bare metal stents (BMS). However,
      inhibition of endothelialization and neointimal formation after SES implantation
      may produce vulnerable plaques. The present study compared the neointimal
      morphology of in-stent restenosis (ISR) between SES and BMS using virtual
      histology-intravascular ultrasound (VH-IVUS). Thirty ISR lesions (SES n = 15, BMS
      n = 15) demonstrated by coronary angiography in 30 patients with stable angina
      pectoris were analyzed with VH-IVUS between 6 months to 3 years after stent
      implantation. Tissue maps were reconstructed from radiofrequency data using VH
      IVUS software. ISR lesions after SES implantation consisted of a significantly
      increased necrotic core (NC) compared to BMS (12.9 vs. 5.6% of neointimal volume,
      p < 0.01). However, the NC in ISR lesions after SES implantation was covered with
      a thick fibrous cap. An increase in the size of NC covered with a thick fibrous
      cap is a characteristic morphological feature of ISR after SES implantation.
      Further studies are needed to clarify whether such a morphological change is
      related to the attenuation of stent thrombosis after SES implantation. 

PMID- 24122585
TI  - Relationships between inflammatory mediators and coronary plaque composition in
      patients with stable angina investigated by ultrasound radiofrequency data
      analysis.
AB  - Inflammation has been recognized as a critical process in the progression of
      coronary atherosclerosis. Virtual Histology-intravascular ultrasound (VH-IVUS)
      has been reported to be a useful tool for tissue characterization of coronary
      atherosclerotic plaque. We investigated relationships between plaque composition
      and inflammation-related factors possibly contributing to atheromatous plaque
      formation and progression, since these are largely unknown. Using VH-IVUS, we
      measured plaque volume and composition at the culprit lesions in patients with
      stable angina undergoing elective percutaneous coronary intervention (n = 33, 39
      de novo lesions), and then analyzed correlations between plaque components and
      serum levels of inflammatory factors in both aorta and culprit coronary artery
      obtained by aspiration using a distal protection device. Linear regression
      analysis revealed that both aortic and coronary LDL cholesterol levels correlated
      with %plaque burden along the culprit lesions (r = 0.535 and 0.539,
      respectively), but with none of the plaque components. Of %plaque components,
      fibro-fatty (FF) correlated positively with both aortic and coronary T cell/B
      cell ratios (r = 0.335 and 0.359, respectively) whereas necrotic core (NC)
      correlated negatively with both aortic and coronary T cell/B cell ratios (r = 
      0.373 and -0.483, respectively). These results suggest that LDL cholesterol may
      be a good marker for total coronary plaque volume whereas the lymphocyte subset
      of T cell/B cell ratios may be a good marker for plaque composition, especially
      FF and NC components volume. 

PMID- 24122586
TI  - Comparison of real-world clinical outcomes between Cypher- and Taxus-eluting
      stents: the GARA-GARA study.
AB  - To evaluate real-world outcomes of PCI in unselected individuals using sirolimus
      eluting (SESs) or paclitaxel-eluting stents (PESs) in a single-center randomized
      trial. Eight hundred consecutive patients (919 lesions) with coronary artery
      disease were randomized to receive SES or PES implantation. In-hospital, mid
      term, and 1-year clinical and angiographical outcomes in both groups were
      compared. MACEs were defined as cardiac death, myocardial infarction, CABG and
      target vessel revascularization (TLR). Follow-up angiography was performed in
      80.7% of patients. The baseline clinical characteristics were similar in both
      groups. Pre- and postprocedural reference vessel diameter, minimum length
      diameter, and diameter stenosis (%DS) were similar in both groups, as was
      incidence of in-hospital and mid-term MACEs. SESs significantly reduced the risk
      of TLR, compared with PESs (SES = 5.5%, PES = 10.5%). The superiority of SESs for
      TLR was also demonstrated with regard to small vessel lesions (stent diameter
      <2.5 mm) (SES = 6.0%, PES = 15.9%), whereas larger vessel (stent diameter >2.5
      mm) lesions did not differ between groups (SES = 5.3%, PES = 8.4%). The safety
      and efficacy of both DESs were nearly equivalent. SESs, however, were superior to
      PESs in reducing mid-term TLR, particularly in the small vessel lesion subsets. 

PMID- 24122587
TI  - Incidence and risk factors of vascular complications following endovascular
      treatment of peripheral arterial disease via the popliteal artery.
AB  - To evaluate vascular complications associated with endovascular treatment (EVT)
      of peripheral arterial disease (PAD) through the popliteal artery and to identify
      the risk factors for these complications. Between November 2005 and January 2009,
      63 patients with PAD received EVT via the popliteal artery. Retrograde (n = 58)
      and antegrade (n = 5) transpopliteal procedures were performed to target 77
      lesions, including 12 distal to the trifurcation. Thirty-five punctures were
      performed under ultrasound guidance and 7 under angiographic guidance; 21
      punctures were performed without any guidance. Vascular complications were
      evaluated by physical examination and duplex ultrasonography. Vascular
      complications at the popliteal puncture site occurred in 8 patients (12.7%): 6
      hematomas and 2 arteriovenous fistulas (AVF). Seven of 24 patients receiving
      hemodialysis (HD) (29%) had significantly higher complications (P = 0.004)
      compared with 1 of 39 patients not receiving hemodialysis (non-HD) (2.6%). HD
      alone was also a significant risk factor for hematoma (P = 0.010). Both AVF
      occurred in HD patients (P = 0.141), and one occurred despite ultrasound-guided
      puncture. Ultrasound-guided puncture showed no significant improvement in
      reducing both complications. The combination of antiplatelet and anticoagulant
      therapy showed no statistical significance in overall complications. In non-HD
      patients, the transpopliteal approach in the EVT of PAD seems to be safe. More
      attention should be paid to HD patients when using the transpopliteal approach
      due to a higher complication rate. 

PMID- 24122588
TI  - Importance of measuring the fractional flow reserve in patients receiving
      hemodialysis.
AB  - Angiography is not always an accurate indicator of physiologically significant
      stenosis. We examined the usefulness of functional evaluation of coronary
      stenosis severity by determining the fractional flow reserve (FFR) using a
      pressure wire in patients who received hemodialysis with angiographically
      intermediate lesions. We recruited 44 patients with intermediate lesions; of
      these, 22 were undergoing hemodialysis while 22 were not. Quantitative coronary
      angiography (QCA) was performed to measure the minimal lumen diameter (MLD) and
      calculate the percent diameter stenosis (%DS). The FFR was calculated as the
      ratio of the coronary pressure at the distal stenotic site to the mean aortic
      pressure during maximum hyperemia. In each group, we investigated the
      relationship between the FFR and %DS and FFR and MLD. The patients in the
      hemodialysis group were significantly younger and had more calcified and type
      B2/C lesions than those in the non-dialysis group. Although the FFR was
      correlated with both %DS (r = 0.71, p < 0.01) and MLD (r = 0.58, p < 0.01) in the
      non-dialysis group, the FFR was not correlated with either MLD or %DS in the
      hemodialysis group. In the hemodialysis group, there was a discordance between
      the QCA- and FFR-based assessments of the severity of coronary stenosis. In
      patients receiving hemodialysis, both anatomical and functional assessments
      should be conducted to determine the physiological significance of the stenosis
      accurately. 

PMID- 24122589
TI  - Association of the use of proton pump inhibitors with adverse cardiovascular and
      bleeding outcomes after percutaneous coronary intervention in the Japanese real
      world clinical practice.
AB  - Previous studies have shown inconsistent results regarding the effects of
      concomitant use of clopidogrel and proton pump inhibitors (PPI) on cardiovascular
      outcomes. We sought to evaluate the clinical impact of PPI-use in patients
      treated with thienopyridines after percutaneous coronary intervention (PCI) in a
      large Japanese observational database. Among 12446 patients discharged alive on
      thienopyridines (ticlopidine 90.4% and clopidogrel 9.6%), 3223 patients were
      treated with PPIs and 9223 patients without PPI at the time of hospital
      discharge. The PPI group included more patients with co-morbidities than the non
      PPI group. The adjusted hazard ratio (HR) of PPI-use for a composite of
      cardiovascular death, myocardial infarction, and stroke was 1.26 (95% confidence
      interval (CI) 1.09-1.47, p = 0.002). The adjusted HR of PPI-use for bleeding was
      1.26 (95% CI 1.05-1.52, p = 0.013). Cardiovascular and bleeding outcomes were not
      different among the three groups receiving three different types of PPI. The
      negative effect of PPI on cardiovascular outcome was consistently seen in both
      drug-eluting stent (DES) [HR 1.31 (95% CI 1.07-1.6, p = 0.0097)] and non-DES
      strata [HR 1.25 (95% CI: 0.99-1.57, p = 0.057)] (Interaction p = 0.79) despite
      the fact that the duration of thienopyridine administration was significantly
      longer in patients receiving DES. In conclusion, cardiovascular outcomes after
      PCI were significantly worse in patients with PPI than in patients without PPI in
      the Japanese real clinical practice. However, the observed poorer cardiovascular
      outcome in patients receiving PPI was most likely to be related to residual
      confounding and seemed not causally related to attenuation of antiplatelet effect
      of thienopyridine through interaction with PPI. 

PMID- 24122590
TI  - Long-term safety and efficacy of sirolimus-eluting stents versus bare-metal
      stents in real world clinical practice in Japan.
AB  - Long-term safety and efficacy of drug-eluting stents remains controversial. The
      CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored
      multi-center registry enrolling consecutive patients undergoing first coronary
      revascularization in 26 centers in Japan. We compared 3-year outcome between
      patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare
      metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was
      associated with significantly lower adjusted risk for all-cause death [hazard
      ratio (HR) [95% confidence interval (CI)] 0.72 (0.59-0.87), P = 0.0007], which
      was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48
      0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63-1.07), P =
      0.15], myocardial infarction [HR (95% CI) 0.73 (0.51-1.03), P = 0.07] and
      definite stent thrombosis [HR (95% CI) 0.62 (0.35-1.09), P = 0.1] was not
      different between the two groups. Despite longer duration of thienopyridine
      administration, SES-use was associated with significantly lower risk for bleeding
      [HR (95% CI) 0.75 (0.6-0.95), P = 0.02] and similar risk for stroke [HR (95% CI)
      1.0 (0.75-1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was
      markedly lower in the SES group [HR (95% CI) 0.42 (0.36-0.48), P < 0.0001]. The
      direction and magnitude of the effect of SES relative to BMS in patients
      presenting acute myocardial infarction (AMI) were similar to those in patients
      presenting otherwise. In conclusion, SES-use as compared with BMS-use was
      associated with marked reduction of TLR without any increases in death,
      myocardial infarction, stent thrombosis, stroke and bleeding in real world
      clinical practice regardless of clinical presentation including AMI. 

PMID- 24122591
TI  - Clinical outcomes of the placement of a drug-eluting stent with the use of
      RotablatorTM in dialytic patients: in comparison with non-dialytic patients.
AB  - Much remains unknown about the clinical outcomes of drug-eluting stent (DES)
      implantations following ablation by the RotablatorTM in dialytic patients. The
      purpose of this study was to examine these outcomes. Of the 43 patients who
      underwent elective DES implantation following ablation with the RotablatorTM-17
      lesions on 12 dialytic patients were designated to Group H and 54 lesions on 31
      non-dialytic patients were designated to Group N. QCA data, the rate of
      restenosis and the avoidance rate of cardiac events at the chronic phase (920 +/-
      446 days) were studied. The age of patients in Group N was significantly older
      (60 +/- 8 years old in Group H vs. 73 +/- 7 in Group N, p < 0.05). The rate of DM
      complication was significantly higher in Group H (75.0% in Group H vs. 32.0% in
      Group N, p < 0.05). The late loss was 1.18 +/- 0.97 mm in Group H and 0.38 +/-
      0.53 mm in Group N, or significantly greater in Group H (p < 0.05). The
      restenosis rate was also higher in group H. (42.9% in Group H and 6.0% in Group
      N). The avoidance rate of cardiac events at the chronic phase was significantly
      lower in Group H. The study suggested that in patients who received DES with the
      use of the RotablatorTM, clinical outcomes were poorer in dialytic patients than
      in non-dialytic patients. 

PMID- 24122592
TI  - Calcified plaque rupture and very late stent thrombosis after bare-metal stent
      implantation.
AB  - Very late stent thrombosis (>1 year: VLST) is a major concern in the drug-eluting
      stent (DES) era. VLST occurs not only in patients implanted with DESs but also in
      those implanted with bare-metal stents (BMSs). We examined intravascular
      ultrasound (IVUS) findings in patients with VLST after BMS implantation. Five
      consecutive patients presented with VLST as ST elevation myocardial infarction.
      VLST occurred at a mean of 9.5 years after BMS implantation. In the IVUS
      findings, the minimum stent area was 7.8 +/- 1.2 mm(2). None of the patients had
      incomplete stent apposition or stent underexpansion, which was defined as a stent
      expansion index of <0.8. The mean stent expansion index was 1.01. Calcium
      deposits in the previous stented segment were observed in 4 patients (80%), and a
      total of 14 calcium deposits were observed in all patients. The calcification
      pattern was superficial (78.5%) and spotty (57.1%) within a calcium arc of <90
      degrees . The mean calcium arc was 72.5 degrees  +/- 88.5 degrees . A ruptured
      plaque with an intraluminal flap was detected in all cases. According to the IVUS
      findings of ruptured plaque and calcium deposits, VLST after BMS might be caused
      by a thrombus formation subsequent to a calcified atherosclerotic plaque rupture.

PMID- 24122593
TI  - Superior vena caval stenting for idiopathic mediastinal fibrosis.
AB  - Relief of superior vena caval (SVC) syndrome due to non-neoplastic mediastinal
      disease is a challenge. Surgically created bypass grafts have poor long term
      patency with significant procedural morbidity. We report a case of SVC syndrome,
      caused by Idiopathic mediastinal fibrosis, treated percutaneously by balloon
      angioplasty with nitinol self expanding stent. 

PMID- 24122594
TI  - Very late stent thrombosis and neointimal plaque rupture after implantation of
      sirolimus-eluting stents: observations with angiography, IVUS and OCT.
AB  - Drug-eluting stent (DES) dramatically reduces the incidence of restenosis and
      rates of target lesion revascularization. Although several reports suggest that
      very late stent thrombosis could occur in patients after DES implantation,
      neointimal plaque rupture may be uncommon in the patients treated with DES
      compared with bare-metal stent. It is unclear that the reason why the patient in
      acute coronary syndrome (ACS) treated with DES has a high frequency of very late
      stent thrombosis and pathophysiological mechanisms of neointimal plaque rupture
      after DES implantation. We report a case of very late stent thrombosis with the
      findings of neontimal plaque rupture as well as incomplete stent apposition 4
      years after sirolimus-eluting stent implantation in ACS. 

PMID- 24122595
TI  - Spontaneous isolated superior mesenteric artery dissection treated under
      intravascular ultrasound guidance.
AB  - While endovascular treatment for superior mesenteric artery dissection has
      recently been adopted its effectiveness remains debatable. We performed
      endovascular stent placement in the acute phase of superior mesenteric artery
      dissection without any preceding medical therapy and obtained a successful
      outcome. Intravascular ultrasound guidance was useful for confirming the location
      of the guidewire in the true lumen. 

PMID- 24122596
TI  - Provisional T stenting following alternating rotational atherectomy for severely
      calcified left main stenosis in a very old male.
AB  - An 88-year-old male was referred to our medical center for the treatment of
      severe angina pectoris. Coronary angiography revealed severely calcified tight
      stenosis in the left main (LM), the left circumflex (LCX) ostium, and the
      proximal portion of the left anterior descending (LAD) artery (Medina 1, 1, 1).
      We performed T-stenting with two everolimus-eluting stents. Prior to T-stenting,
      we performed alternating rotational atherectomy (RA) of the vessel segments from
      the LM to LCX and from the LM to LAD. The effectiveness of alternating RA was
      confirmed by a "pendulous calcification" at the carina of the LM bifurcation. 

PMID- 24122597
TI  - A case of adult patient ductus arteriosus with congestive heart failure and
      severe mitral regurgitation.
AB  - A 46-year-old woman presented herself at the hospital with progressive effort
      dyspnea and lower limbs edema which she had had for 3 months. She had a history
      of surgical ligation of patent ductus arteriosus (PDA) at the age of 25-year-old.
      A transthoracic cardiac ultrasonography showed left ventricular dilatation,
      severe functional mitral regurgitation, and a recurrent shunt of PDA.
      Percutaneous coil closure of PDA was performed and 6 months after the procedure,
      resolution of functional mitral regurgitation and normalization of left atrial
      and ventricular sizes were achieved. 

PMID- 24122598
TI  - The impact of Rho-kinase inhibitor, "Fasudil", intracoronary bolus administration
      to improve refractory coronary vasospasm.
AB  - A 57 year-old man presenting with acute inferior myocardial infarction underwent
      percutaneous coronary intervention. Following the placement of TAXUS Liberte 2.5
      * 24 mm (Boston Sientific, USA), for 99% stenosis with delay, severe vasospasm
      occurred at distal portion of the stent. However, persistent vasospasm was
      observed despite ISDN (isosorbide dinitrate), nitroprusside, and nicorandil, were
      used to control the repetitive vasospasm during the course of 90 min. Then the
      decision was made to use intra-coronary bolus of Rho-kinase inhibitor, fasudil
      100 MUg/kg. Then the vasospasm resolved and no recurrence was observed during the
      procedure and hospital stay for 25 days. We experienced a valuable case, whose
      repetitive vasospasm was resolved with intracoronary administration of Rho kinase
      inhibitor. 

PMID- 24122599
TI  - Treating coil migration in combination therapy involving stenting and coiling for
      a wide-necked renal aneurysm.
AB  - A man with a wide-necked renal artery aneurysm underwent combination therapy
      involving stenting and coiling to embolize it. However, a large section of one of
      the coils had migrated outside the stent implanted across the orifice of the
      aneurysm. After repositioning the migrated coil inside the stent, the
      implantation of another stent together with sandwiching of the coil between two
      stents repaired the prolapsed coil. This report describes precautions that should
      be taken during combination therapy involving stenting and coiling to embolize a
      wide-necked aneurysm. 

PMID- 24122600
TI  - A patient with significant slow-flow phenomenon during percutaneous coronary
      intervention for ST elevation myocardial infarction associated with scattered
      necrotic core by virtual histology intravascular ultrasound.
AB  - A 68-year-old man with acute ST elevation myocardial infarction (STEMI) underwent
      emergent coronary angiography which showed total occlusion in the proximal right
      coronary artery (RCA). Gray-scale intravascular ultrasound (IVUS) revealed the
      culprit lesion was expansively remodeled and contained ruptured and echolucent
      plaques with spotty calcification, whereas thin-capped fibroatheroma and a large
      amount of scattered necrotic core were observed by virtual histology (VH)-IVUS.
      After stent implantation in the proximal RCA under a filter protection, filter-no
      reflow phenomenon occurred and thrombus-like defect was observed in the mid RCA.
      Under these conditions, VH-IVUS detected a large amount of scattered necrotic
      core in the mid RCA. We suggest scattered necrotic core detected by VH-IVUS may
      be associated with slow-flow phenomenon during percutaneous coronary intervention
      in our patient with STEMI. 

PMID- 24122601
TI  - A successful treatment for in-stent restenosis using a 4-French guiding catheter
      with optical coherence tomography guidance.
AB  - An 83-year-old woman was admitted due to effort related chest squeezing over the
      duration of 5 months. A coronary angiogram revealed significant in-stent
      restenosis at proximal left anterior descending artery. Optical coherence
      tomography (OCT) image acquisition was successfully performed using a non
      occlusive technique. Restenotic tissue consisting of eccentric layers was
      observed by the OCT. The only imaging method of intracoronary evaluation using a
      4F guiding catheter is an OCT. An OCT assessment was helpful for the percutaneous
      coronary intervention using a 4F guiding catheter. 

PMID- 24122602
TI  - A perspective of food safety laws in Mexico.
AB  - Mexico, with a population of 112 million, is one of the most interesting
      countries in the world with regard to food, hunger, domestic food consumption,
      tourism and international trade, and it deserves an in-depth study to explain the
      status of its food safety laws. Mexico has a strong and stable emerging economy
      and is the second country worldwide with regard to the number of free-trade
      agreements. Nevertheless, more than half the population lives in poverty.
      However, Mexico is a huge market for food consumption because, in addition to its
      own population, it receives 20 million international tourists per year. So, multi
      national food companies have representatives and facilities throughout the
      country. This scenario may explain the evolution of food safety laws in Mexico,
      as well as the challenges that must be faced in order to achieve food safety.

PMID- 24122604
TI  - Vitamin D and the cardiovascular system: an overview of the recent literature.
AB  - Since the discovery that the enzyme catalyzing the synthesis of the most active
      natural vitamin D metabolite(calcitriol) and the vitamin D-specific receptor
      (VDR)were expressed in a wide range of tissues and organs, not only involved in
      the mineral metabolism (MM), there has been increasing interest on the putative
      'non classical' roles of vitamin D metabolites, particularly on their possible
      effects on the cardiovascular (CV) system. These hypothetical CV effects of
      vitamin D gained particular interesting the nephrology field, given the high
      prevalence of CV disease in patients affected by either acute or chronic kidney
      diseases. However, notwithstanding a huge amount of experimental data suggesting
      a possible protective role of vitamin D on the CV system, the conclusions of two
      recent meta-analyses from the Cochrane group and a recent statement from the
      Institute of Medicine, based on a complete revision of the available data,
      concluded that there is no clear evidence for a role of vitamin D other than that
      strictly associated with bone health. However, a continuous and increasing flow
      of new studies still continues to add information on this topic. In the present
      review, we have tried to critically address the data added on this topicin the
      last 2 years, considering separately the experimental,observational, and
      intervention studies that have appeared in PubMed in the last 2 years, discussing
      the data providing proof, pro or contra, the involvement of vitamin D in CV
      disease, both in the absence or presence of kidney function impairment.

PMID- 24122603
TI  - Enhanced production of coenzyme Q10 by self-regulating the engineered MEP pathway
      in Rhodobacter sphaeroides.
AB  - Fine-tuning the expression level of an engineered pathway is crucial for the
      metabolic engineering of a host toward a desired phenotype. However, most
      engineered hosts suffer from nonfunctional protein expression, metabolic
      imbalance, cellular burden or toxicity from intermediates when an engineered
      pathway is first introduced, which can decrease production of the desired
      product. To circumvent these obstacles, we developed a self-regulation system
      utilizing the trc/tac promoter, LacI(q) protein and ribosomal binding sites
      (RBS). With the purpose of improving coenzyme Q10 (CoQ10 ) production by
      increasing the decaprenyl diphosphate supplement, enzymes DXS, DXR, IDI, and IspD
      were constitutively overexpressed under the control of the trc promoter in
      Rhodobacter sphaeroides. Then, a self-regulation system combining a set of RBSs
      for adjusting the expression of the LacI(q) protein was applied to tune the
      expression of the four genes, resulting in improved CoQ10 production. Finally,
      another copy of the tac promoter with the UbiG gene (involved in the ubiquinone
      pathway of CoQ10 biosynthesis) was introduced into the engineered pathway. By
      optimizing the expression level of both the upstream and downstream pathway,
      CoQ10 production in the mutants was improved up to 93.34 mg/L (7.16 mg/g DCW),
      about twofold of the wild-type (48.25 mg/L, 3.24 mg/g DCW).

PMID- 24122605
TI  - An ultrasound-based computer-aided diagnosis tool for steatosis detection.
AB  - Liver steatosis is a common disease usually associated with social and genetic
      factors. Early detection and quantification is important since it can evolve to
      cirrhosis. In this paper, a new computer-aided diagnosis (CAD) system for
      steatosis classification, in a local and global basis, is presented. A Bayes
      factor is computed from objective ultrasound textural features extracted from the
      liver parenchyma. The goal is to develop a CAD screening tool to help in the
      steatosis detection. Results showed an accuracy of 93.33%, with a sensitivity of
      94.59% and specificity of 92.11%, using the Bayes classifier. The proposed CAD
      system is a suitable graphical display for steatosis classification. 

PMID- 24122607
TI  - Accelerometry-based home monitoring for detection of nocturnal hypermotor
      seizures based on novelty detection.
AB  - Nocturnal home monitoring of epileptic children is often not feasible due to the
      cumbersome manner of seizure monitoring with the standard method of video/EEG
      monitoring. We propose a method for hypermotor seizure detection based on
      accelerometers attached to the extremities. From the acceleration signals,
      multiple temporal, frequency, and wavelet-based features are extracted. After
      determining the features with the highest discriminative power, we classify
      movement events in epileptic and nonepileptic movements. This classification is
      only based on a nonparametric estimate of the probability density function of
      normal movements. Such approach allows us to build patient-specific models to
      classify movement data without the need for seizure data that are rarely
      available. If, in the test phase, the probability of a data point (event) is
      lower than a threshold, this event is considered to be an epileptic seizure;
      otherwise, it is considered as a normal nocturnal movement event. The mean
      performance over seven patients gives a sensitivity of 95.24% and a positive
      predictive value of 60.04%. However, there is a noticeable interpatient
      difference. 

PMID- 24122606
TI  - Prediction of periventricular leukomalacia occurrence in neonates after heart
      surgery.
AB  - This paper is concerned with predicting the occurrence of periventricular
      leukomalacia (PVL) using vital and blood gas data which are collected over a
      period of 12 h after the neonatal cardiac surgery. A data mining approach has
      been employed to generate a set of rules for classification of subjects as
      healthy or PVL affected. In view of the fact that blood gas and vital data have
      different sampling rates, in this study we have divided the data into two
      categories: 1) high resolution (vital), and 2) low resolution (blood gas), and
      designed a separate classifier based on each data category. The developed
      algorithm is composed of several stages; first, a feature pool has been extracted
      from each data category and the extracted features have been ranked based on the
      data reliability and their mutual information content with the output. An optimal
      feature subset with the highest discriminative capability has been formed using
      simultaneous maximization of the class separability measure and mutual
      information of a set. Two separate decision trees (DTs) have been developed for
      the classification purpose and more importantly to discover hidden relationships
      that exist among the data to help us better understand PVL pathophysiology. The
      DT result shows that high amplitude 20 min variations and low sample entropy in
      the vital data and the defined out of range index as well as maximum rate of
      change in blood gas data are important factors for PVL prediction. Low sample
      entropy represents lack of variability in hemodynamic measurement, and constant
      blood pressure with small fluctuations is an important indicator of PVL
      occurrence. Finally, using the different time frames of data collection, we show
      that the first 6 h of data contain sufficient information for PVL occurrence
      prediction.

PMID- 24122608
TI  - Design and development of a virtual reality simulator for advanced cardiac life
      support training.
AB  - The use of virtual reality (VR) training tools for medical education could lead
      to improvements in the skills of clinicians while providing economic incentives
      for healthcare institutions. The use of VR tools can also mitigate some of the
      drawbacks currently associated with providing medical training in a traditional
      clinical environment such as scheduling conflicts and the need for specialized
      equipment (e.g., high-fidelity manikins). This paper presents the details of the
      framework and the development methodology associated with a VR-based training
      simulator for advanced cardiac life support, a time critical, team-based medical
      scenario. In addition, we also report the key findings of a usability study
      conducted to assess the efficacy of various features of this VR simulator through
      a postuse questionnaire administered to various care providers. The usability
      questionnaires were completed by two groups that used two different versions of
      the VR simulator. One version consisted of the VR trainer with it all its
      features and a minified version with certain immersive features disabled. We
      found an increase in usability scores from the minified group to the full VR
      group.

PMID- 24122609
TI  - Part-based multiderivative edge cross-sectional profiles for polyp detection in
      colonoscopy.
AB  - This paper presents a novel technique for automated detection of protruding
      polyps in colonoscopy images using edge cross-section profiles (ECSP). We propose
      a part-based multiderivative ECSP that computes derivative functions of an edge
      cross-section profile and segments each of these profiles into parts. Therefore,
      we can model or extract features suitable for each part. Our features obtained
      from the parts can effectively describe complex properties of protruding polyps
      including the shape of the parts, texture, and protrusion and smoothness of the
      polyp surface. We evaluated our method against two existing polyp image detection
      techniques on 42 different polyps, including those with little protrusion. Each
      polyp has a large variation of appearance in viewing angles, light conditions,
      and scales in different images. The evaluation showed that our technique
      outperformed the existing techniques in both accuracy and analysis time. Our
      method has a higher area under the free-response receiver operating
      characteristic curve. For instance, when both techniques have a true positive
      rate for polyp image detection of 81.4%, the average number of false regions per
      image of our technique is 0.32 compared to 1.8 of the best existing technique
      under study. Additionally, our technique can precisely mark edges of candidate
      polyp regions as visual feedback. These results altogether indicate that our
      technique is promising to provide visual feedback of polyp regions in clinical
      practice.

PMID- 24122610
TI  - Improved semisupervised adaptation for a small training dataset in the brain
      computer interface.
AB  - One problem in the development of brain-computer interface (BCI) systems is to
      minimize the amount of subject training on the premise of accurate
      classification. Hence, the challenge is how to train the BCI system effectively
      especially in the scenario with small amount of training data. In this paper, we
      introduce improved semisupervised adaptation based on common spatial pattern
      (CSP) features. The feature extraction and classification are performed jointly
      and iteratively. In the iteration step, training data are expanded by part of the
      testing data with labels which are predicted by a linear discriminant analysis
      classifier and/or a Bayesian linear discriminant analysis classifier in the
      previous iteration. Then CSP features are reextracted from the expanded training
      data, and the classifiers are retrained. Both self-training and cotraining
      paradigms are proposed for the improved semisupervised adaptation. Throughout the
      investigation on different number of initial training trials, we find that when a
      small number of training trials are used, e.g., a training session contains no
      more than 30 trials, similar classification performance to that of large training
      data items (40-50 trials) can be achieved. Effectiveness of the algorithms is
      verified by two competition datasets. Compared with several existing algorithms,
      the proposed semisupervised algorithms show improvements in classification
      accuracy for most of the competition datasets especially in the case of small
      training data.

PMID- 24122611
TI  - EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer.
AB  - BACKGROUND: Combined chemoradiation therapy is the gold standard in the treatment
      of squamous cell anal cancer (SCAC). However, even if the response rate is very
      high, many patients eventually relapse or experience a reccurrence, thus
      requiring an invasive surgical procedure that has severe side effects. Most SCAC
      tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is
      reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated
      by anecdotal reports. Promising results obtained in other solid tumors, both
      squamous and non-squamous, have revealed that an increase in the EGFR gene copy
      number may predict the efficacy of anti-EGFR therapies, while the presence of
      mutations in downstream members of the EGFR pathway may confer resistance. These
      markers have been only sporadically considered in SCAC. METHODS: We investigated
      the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot
      spots mutations using sequencing analysis in a cohort of 84 patients affected by
      SCAC. RESULTS: Twenty-eight patients (34%) showed an increase in EGFR gene copy
      number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene
      mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations
      were found in the BRAF gene. CONCLUSIONS: The characterization of the EGFR
      pathway may help in identifying different subgroups of SCAC that have specific
      molecular features, which may have implications in what targeted therapies are
      used to treat each patient.

PMID- 24122612
TI  - Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic
      risk marker for early-onset myocardial infarction by genome-wide linkage
      analysis.
AB  - BACKGROUND: Myocardial infarction (MI) is a leading cause of death worldwide.
      Given that a family history is an independent risk factor for coronary artery
      disease, genetic variants are thought to contribute directly to the development
      of this condition. The identification of susceptibility genes for coronary artery
      disease or MI may thus help to identify high-risk individuals and offer the
      opportunity for disease prevention. METHODS AND RESULTS: We designed a 5-step
      protocol, consisting of a genome-wide linkage study followed by association
      analysis, to identify novel genetic variants that confer susceptibility to
      coronary artery disease or MI. A genome-wide affected sib-pair linkage study with
      221 Japanese families with coronary artery disease yielded a statistically
      significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI.
      Further association analysis implicated Alstrom syndrome 1 gene (ALMS1) as a
      candidate gene within the linkage region. Validation association analysis
      revealed that representative single-nucleotide polymorphisms of the ALMS1
      promoter region were significantly associated with early-onset MI in both
      Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding
      region identified a glutamic acid repeat polymorphism in exon 1, which was
      subsequently found to be associated with early-onset MI. CONCLUSIONS: The
      glutamic acid repeat polymorphism of ALMS1 identified in the present study may
      provide insight into the pathogenesis of early-onset MI.

PMID- 24122613
TI  - Association of neuroimmune guidance cue netrin-1 and its chemorepulsive receptor
      UNC5B with atherosclerotic plaque expression signatures and stability in
      human(s): Tampere Vascular Study (TVS).
AB  - BACKGROUND: Macrophage (MPhi) infiltration and smooth muscle cell (SMC)
      proliferation are hallmarks of atherosclerosis and unstable plaques. Neuroimmune
      guidance cue 1 (netrin-1 [NTN1]) plays a critical role controlling MPhi
      trafficking and SMC activation. Characterization of expression of NTN1 and its
      receptors and their association with plaque stability in human(s) is lacking.
      METHODS AND RESULTS: The expression of NTN1 and its receptors did not differ in
      either whole blood or circulating monocytes from patients with coronary artery
      disease (n=55) compared with healthy controls (n=45). However, NTN1 was
      downregulated (-2.9-fold; P<0.0001) and UNC5B upregulated (2.2-fold; P<0.0001) in
      atherosclerotic plaques (n=68), whereas there were no differences in other NTN1
      receptors compared with histologically normal controls (n=28). Increased UNC5B
      expression is associated with histologically more stable plaques (P=0.011). NTN1
      expression correlated positively with SMC markers and signatures and negatively
      with inflammatory markers and M1 and especially M2 signatures in the
      atherosclerotic plaques. UNC5B clustering correlated positively with inflammatory
      and MPhi markers. NTN1 protein colocalized with CD68-positive cells of monocytic
      origin and muscle-actin-specific-antibody (HHF3)-positive cells indicative of
      SMCs in the plaques and only with SMCs in the control samples. NTN1 protein was
      highly expressed in the intimal layer of the control vessels. CONCLUSIONS:
      Present findings provide support for the hypothesis that dysregulation of
      expression of NTN1 in SMCs and its chemorepulsive receptor UNC5B in macrophages
      are involved in the development of atherosclerosis and unstable plaques.

PMID- 24122614
TI  - The effect of sound on visual fidelity perception in stereoscopic 3-D.
AB  - Visual and auditory cues are important facilitators of user engagement in virtual
      environments and video games. Prior research supports the notion that our
      perception of visual fidelity (quality) is influenced by auditory stimuli.
      Understanding exactly how our perception of visual fidelity changes in the
      presence of multimodal stimuli can potentially impact the design of virtual
      environments, thus creating more engaging virtual worlds and scenarios.
      Stereoscopic 3-D display technology provides the users with additional visual
      information (depth into and out of the screen plane). There have been relatively
      few studies that have investigated the impact that auditory stimuli have on our
      perception of visual fidelity in the presence of stereoscopic 3-D. Building on
      previous work, we examine the effect of auditory stimuli on our perception of
      visual fidelity within a stereoscopic 3-D environment.

PMID- 24122615
TI  - Foraging swarms as Nash equilibria of dynamic games.
AB  - The question of whether foraging swarms can form as a result of a noncooperative
      game played by individuals is shown here to have an affirmative answer. A dynamic
      game played by N agents in 1-D motion is introduced and models, for instance, a
      foraging ant colony. Each agent controls its velocity to minimize its total work
      done in a finite time interval. The game is shown to have a unique Nash
      equilibrium under two different foraging location specifications, and both
      equilibria display many features of a foraging swarm behavior observed in
      biological swarms. Explicit expressions are derived for pairwise distances
      between individuals of the swarm, swarm size, and swarm center location during
      foraging. 

PMID- 24122616
TI  - Evolvable rough-block-based neural network and its biomedical application to
      hypoglycemia detection system.
AB  - This paper focuses on the hybridization technology using rough sets concepts and
      neural computing for decision and classification purposes. Based on the rough set
      properties, the lower region and boundary region are defined to partition the
      input signal to a consistent (predictable) part and an inconsistent (random)
      part. In this way, the neural network is designed to deal only with the boundary
      region, which mainly consists of an inconsistent part of applied input signal
      causing inaccurate modeling of the data set. Owing to different characteristics
      of neural network (NN) applications, the same structure of conventional NN might
      not give the optimal solution. Based on the knowledge of application in this
      paper, a block-based neural network (BBNN) is selected as a suitable classifier
      due to its ability to evolve internal structures and adaptability in dynamic
      environments. This architecture will systematically incorporate the
      characteristics of application to the structure of hybrid rough-block-based
      neural network (R-BBNN). A global training algorithm, hybrid particle swarm
      optimization with wavelet mutation is introduced for parameter optimization of
      proposed R-BBNN. The performance of the proposed R-BBNN algorithm was evaluated
      by an application to the field of medical diagnosis using real hypoglycemia
      episodes in patients with Type 1 diabetes mellitus. The performance of the
      proposed hybrid system has been compared with some of the existing neural
      networks. The comparison results indicated that the proposed method has improved
      classification performance and results in early convergence of the network. 

PMID- 24122617
TI  - Synchronization and adaptive control of an array of linearly coupled reaction
      diffusion neural networks with hybrid coupling.
AB  - In this paper, we propose a general array model of coupled reaction-diffusion
      neural networks with hybrid coupling, which is composed of spatial diffusion
      coupling and state coupling. By utilizing the Lyapunov functional method combined
      with the inequality techniques, a sufficient condition is given to ensure that
      the proposed network model is synchronized. In addition, when the external
      disturbances appear in the network, a criterion is obtained to guarantee the
      Hinfinity synchronization of the network. Moreover, some adaptive strategies to
      tune the coupling strengths among network nodes are designed for reaching
      synchronization and Hinfinity synchronization. Some criteria for synchronization
      and Hinfinity synchronization are derived by using the designed adaptive laws.
      Numerical simulations are presented finally to demonstrate the effectiveness of
      the obtained theoretical results. 

PMID- 24122618
TI  - Effects of ethanol on social approach and 50 kHz ultrasonic vocalization
      production in adolescent male Sprague-Dawley rats.
AB  - Low doses of ethanol have been shown to facilitate social behavior in adolescent
      rats. The present study sought to investigate whether this ethanol effect is
      associated with increases in the incentive salience of social stimuli when
      assessed via approach behavior toward a peer (separated from the experimental
      animal by a mesh barrier) and 50 kHz ultrasonic vocalization (USV) production in
      that context. A 0.5 g/kg ethanol dose was found to increase social
      approach/investigation of adolescent male Sprague-Dawley rats during the first 5
      min of the 10 min test whereas 50 kHz USV production was elevated by 0.25 g/kg
      during the last 5 min of testing. 50 kHz USV production and social approach were
      generally not correlated, indicating a clear dissociation between these measures.
      This is the first study to demonstrate that ethanol-induced social facilitation
      in adolescents is associated with an ethanol-induced increase in the incentive
      salience of social stimuli.

PMID- 24122619
TI  - Bilateral cochlear implantation in children and the impact of the inter-implant
      interval.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effectiveness of simultaneous versus
      sequential bilateral cochlear implantation on postoperative outcomes in children
      with bilateral deafness and to evaluate the impact of the inter-implant interval
      and age at second implantation on postoperative outcomes in children who already
      received their first cochlear implant. DATA SOURCES: PubMed, Embase, and Web of
      Science. REVIEW METHODS: All studies comparing the effects of simultaneous with
      sequential bilateral cochlear implantation on postoperative outcomes and those
      evaluating the impact of the inter-implant interval and age at second
      implantation were retrieved. RESULTS: Four studies compared the effects of
      simultaneous with sequential bilateral cochlear implantation. All studies lacked
      randomization. Of these, three reported better speech perception and expressive
      language development at one year of bilateral experience for simultaneous
      cochlear implantation. Of the nineteen publications on the impact of the inter
      implant interval on postoperative outcomes, the risk of bias was low-moderate for
      seven studies which were derived from five different study populations. In two of
      these populations no impact of the inter-implant interval was found, while in
      three a longer inter-implant interval was associated with poorer speech and
      language development. CONCLUSION: Observational studies suggest that simultaneous
      implantation in children may be associated with improved speech and language
      development, and that a prolonged inter-implant interval between both
      implantations may have a negative impact on these postoperative outcomes.
      Randomized trials are, however, needed to demonstrate whether simultaneous
      implantation indeed is superior to sequential bilateral implantation in children
      with bilateral deafness. LEVEL OF EVIDENCE: NA.

PMID- 24122620
TI  - The role of CcTpt1 in scale and early embryo development in common carp (Cyprinus
      carpio, Cyprinidae).
AB  - The full length cDNA sequence of the Tpt1/TCTP (Tumor protein, Translationally
      controlled1) gene was identified from Common Carp (Cyprinus carpio, Cyprinidae),
      and was designated as CcTpt1 gene. The CDS is 510 bp and encodes a 170-amino acid
      peptide with a typical Tpt1 signature 2 domain, and is a typical Tpt1 protein.
      The deduced amino acid sequence of Tpt1 shared significant identity with the Tpt1
      from other animals. A phylogenetic tree analysis revealed that the Common Carp
      Tpt1 protein has the closest genetic relationship and evolutional distance with
      Tpt1 from Medaka (Oryzias Latipes). Analysis by RT-PCR showed that the Tpt1 mRNA
      was detected in heart, liver, gill, kidney, muscle and skin. In embryogenesis,
      the Tpt1 mRNA was expressed gradually stronger from two-cell stage until prim-5
      stage by whole-mount in situ. In larval stage, the Tpt1 was specifically
      expressed at eyes and brain, later at the ear stone, intestines, gills and
      internal organs. In addition, the Tpt1 was also found to be expressed in skin
      matrix being developed into scales and gradually disappeared when the scales were
      fully formed. These data suggested that the CcTpt1 may play important roles in
      early embryogenesis and scale initiation in fish.

PMID- 24122621
TI  - Bringing the Bacon home.

PMID- 24122622
TI  - Chronic hepatitis B management based on standard guidelines in community primary
      care and specialty clinics.
AB  - BACKGROUND AND AIMS: Prior studies have underlined the need for increased
      screening and awareness of chronic hepatitis B (CHB), especially in certain high
      risk populations. However, few studies have examined the patterns of evaluation
      and management of CHB between primary care physicians (PCP) and specialists
      according to commonly-used professional guidelines. Our goal was to examine
      whether necessary laboratory parameters used to determine disease status and
      eligibility for antiviral therapy were performed by PCPs and specialists.
      METHODS: We conducted a retrospective study of 253 treatment-naive CHB patients
      who were evaluated by PCP only (n=63) or by specialists (n=190) for CHB at a
      community multispecialty medical center between March 2007 and June 2009.
      Criteria for CHB management and treatment eligibility were based on the American
      Association for the Study of Liver Diseases 2007 guideline and the US Panel 2006
      algorithm. Required parameters for optimal evaluation for CHB included hepatitis
      B e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT). Preferred
      antiviral agents for CHB included pegylated interferon, adefovir, and entecavir.
      RESULTS: The majority of patients were Asians (90%) and (54%) with a mean age of
      43+/-11.6 years. Compared to PCPs, specialists were more likely to order
      laboratory testing for ALT (94 vs. 86%, P=0.05), HBeAg (67 vs. 41%, P<0.0001) and
      HBV DNA (83 vs. 52%, P<0.0001). The proportion of patients having all three
      laboratory parameters was significantly higher among those evaluated by
      specialists compared to PCP (62 vs. 33%, P<0.0001). A total of 55 patients were
      initiated on antiviral treatment (n=47 by specialists and n=6 by PCPs).
      Lamivudine was prescribed more often by PCPs than specialists (33 vs. 2%,
      P=0.05). Preferred agents were used 96% of the time by specialists compared to
      67% of those treated by PCPs (P=0.05). CONCLUSION: Patients evaluated by
      specialists for CHB are more likely to undergo more complete laboratory
      evaluation and, if eligible, are also more likely to be treated with preferred
      longer-term agents for CHB compared to those evaluated by PCPs only. A
      collaborative model of care involving both PCP and specialists may further
      optimize management of patients with CHB.

PMID- 24122623
TI  - Clinical course of central neurocytoma with malignant transformation-an
      indication for craniospinal irradiation.
AB  - Central neurocytoma is generally considered to be a benign tumor and the
      literature suggests that a cure may be attained by surgery +/- adjuvant focal
      irradiation. However, there is a need for change in the therapeutic strategy for
      the subgroup of patients with aggressive central neurocytoma. An example case is
      presented and the literature on central neurocytoma cases with malignant features
      and dissemination via the cerebrospinal fluid is reviewed and the
      radiotherapeutic strategies available for central neurocytoma treatment is
      discussed. Nineteen cases including the present report with a malignant course
      and cerebrospinal fluid dissemination have been described to date, most of them
      involving an elevated MIB-1 labeling index. Our case exhibited atypical central
      neurocytoma with an initially elevated MIB-1 labeling index (25-30 %). The
      primary treatment included surgery and focal radiotherapy. Three years later the
      disease had disseminated throughout the craniospinal axis. A good tumor response
      and symptom relief were achieved with repeated radiation and temozolomide
      chemotherapy. Central neurocytoma with an initially high proliferation activity
      has a high tendency to spread via the cerebrospinal fluid. The chemo- and
      radiosensitivity of the tumor suggest a more aggressive adjuvant therapy
      approach. Cases with a potential for malignant transformation should be
      identified and treated appropriately, including irradiation of the entire
      neuroaxis and adjuvant chemotherapy may be considered.

PMID- 24122624
TI  - Vocational rehabilitation for enhancing return-to-work in workers with traumatic
      upper limb injuries.
AB  - BACKGROUND: Traumatic upper limb injury is a leading cause of work-related
      disability. After return-to-work (RTW), many survivors of injuries are able to
      regain a quality of life (QoL) comparable with the normal population. Since RTW
      plays an important role in economic productivity and regaining health-related
      QoL, enhancing RTW in workers with traumatic limb injuries is the primary goal of
      rehabilitation. Vocational rehabilitation has been adapted in the field of
      occupational safety and health to enhance the number of injured people returning
      to the labour market, prevent illness, increase well-being, and reduce
      disability. OBJECTIVES: To assess the effects of vocational rehabilitation
      programs in enhancing RTW of workers with traumatic upper limb injuries. SEARCH
      METHODS: We searched OSH UPDATE databases (CISDOC, HSELINE, International
      Bibliographic, NIOSHTIC, NIOSHTIC-2, RILOSH) (up to 10 December 2012), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11),
      MEDLINE through PubMed (up to 15 November 2012), EMBASE (up to 28 November 2012),
      CINAHL (up to 5 May 2013), PsycINFO (up to 7 December 2012), and handsearched the
      reference lists of relevant review articles. SELECTION CRITERIA: We aimed to
      include all randomised controlled trials (RCTs) comparing vocational
      rehabilitation with an alternative (control) intervention such as standard
      rehabilitation, an incomplete form of the vocational rehabilitation intervention
      (such as with limited advice on RTW, referral information, or liaison with
      employer), or waiting-list controls. DATA COLLECTION AND ANALYSIS: Two authors
      independently inspected abstracts and we obtained full papers when necessary.
      When the two authors disagreed about the inclusion of a study, we resolved
      disagreements by discussion. A third author arbitrated when necessary. MAIN
      RESULTS: Our search identified 332 citations. Based on assessments of their
      titles and abstracts, we decided to evaluate the full texts of 15 citations. In
      the end, none of these 15 citations met our inclusion criteria. AUTHORS'
      CONCLUSIONS: There is currently no high-level evidence to support or refute the
      efficacy of vocational rehabilitation in enhancing RTW in workers with traumatic
      upper limb injuries. Since vocational rehabilitation has frequently been provided
      to injured people in occupational settings with the aim of decreasing work
      disability, enhancing RTW, increasing productivity, and containing the welfare
      cost, further high-quality RCTs assessing the efficacy of vocational
      rehabilitation for workers with traumatic upper limb injury are needed to fill
      this gap in knowledge.

PMID- 24122625
TI  - Functional analysis of the extended N-terminal region in PLC-delta1 (MlPLC
      delta1) from the mud loach, Misgurnus mizolepis.
AB  - Mud loach phospholipase C-delta1 (MlPLC-delta1) contains all the characteristic
      domains found in mammalian PLC-delta isozymes (pleckstrin homology domain, EF
      hands, X-Y catalytic region, and C2 domain) as well as an extended 26-amino acid
      (aa)-long N-terminal region that is an alternative splice form of PLC-delta1 and
      is novel to vertebrate PLC-delta. In the present structure-function analysis,
      deletion of the extended N-terminal region caused complete loss of
      phosphatidylinositol (PI)- and phosphatidylinositol 4,5-bisphosphate (PIP2)
      hydrolyzing activity in MlPLC-delta1. Additionally, recombinant full-length MlPLC
      delta1 PLC activity was reduced in a dose-dependent manner by coincubation with
      the 26-aa protein fragment. Using a protein-lipid overlay assay, both full-length
      MlPLC-delta1 and the 26-aa protein fragment had substantial affinity for PIP2,
      whereas deletion of the 26-aa region from MlPLC-delta1 (MlPLC-delta1-deletion)
      resulted in lower affinity for PIP2. These results suggest that the novel N
      terminal exon of MlPLC-delta1 could play an important role in the regulation of
      PLC-delta1.

PMID- 24122626
TI  - Diphenyl diselenide-loaded nanocapsules: preparation and biological distribution.
AB  - Over the past years, organoselenium compounds have been aimed as targets of
      interest in organic synthesis. Diphenyl diselenide [(PhSe)2] is an important
      example of this class showing several pharmacological properties. However, the
      poor water-solubility and its low oral bioavailability may be considered an
      obstruction for the clinical utility of this compound. For this reason, the use
      of nanocapsules is a prominent approach to increase the bioavailability of
      lipophylic molecules. This study aims to prepare diphenyl diselenide-loaded
      nanocapsules with two different concentrations, by interfacial deposition of the
      preformed polymer in order to develop a system to improve its oral
      bioavailability. The drug-loaded nanocapsules with 1.56 and 5 mg ml-1 and
      unloaded nanocapsule suspensions presented macroscopic homogeneous aspect, as
      well as submicronic sizes, low polydispersity, negative zeta potentials and
      slightly acid or neutral pH values. The biological tests of selenium distribution
      in different tissues of mice show a higher bioavailability of the (PhSe)2
      nanocapsules when compared with the free (PhSe)2, both administered by per oral
      route at the dose of 50 mg/kg, showing a prominent influence of the nanocarries
      systems for biological properties of this organochalcogenium compound.

PMID- 24122627
TI  - Population analysis of mesophilic microbial fuel cells fed with carbon monoxide.
AB  - Electricity generation in a microbial fuel cell (MFC) fed with carbon monoxide
      (CO) has been recently demonstrated; however, the microbial ecology of this
      system has not yet been described. In this work the diversity of the microbial
      community present at the anode of CO-fed MFCs was studied by performing
      denaturing gradient gel electrophoresis (DGGE) and high-throughput sequencing
      (HTS) analyses. HTS indicated a significant increase of the archaeal genus
      Methanobacterium and of the bacterial order Clostridiales, notably including
      Clostridium species, while in both MFCs DGGE identified members of the bacterial
      genera Geobacter, Desulfovibrio, and Clostridium, and of the archaeal genera
      Methanobacterium, Methanofollis, and Methanosaeta. In particular, the presence of
      Geobacter sulfurreducens was identified. Tolerance of G. sulfurreducens to CO was
      confirmed by growing G. sulfurreducens with acetate under a 100 % CO atmosphere.
      This observation, along with the identification of acetogens, supports the
      hypothesis of the two-step process in which CO is converted to acetate by the
      carboxidotrophic Bacteria and acetate is then oxidized by CO-tolerant
      electricigenic bacteria to produce electricity.

PMID- 24122628
TI  - Antifungal activity of diketopiperazines and stilbenes against plant pathogenic
      fungi in vitro.
AB  - The present study aimed to investigate antifungal activity of a stilbene and
      diketopiperazine compounds against plant pathogenic fungi, including Phytophthora
      capsici, P. colocasiae, Botrytis cinerea and Colletotrichum gloeosporioides.
      Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations
      (MFC) of stilbenes and diketopiperazines for each fungus were determined using
      microplate method. Best activity was recorded by stilbenes against P. capsici and
      P. colocasiae. All four test compounds were effective in inhibiting different
      stages of the life cycle of test fungi. Stilbenes were more effective than
      diketopiperazines in inhibiting mycelial growth and inhibiting different stages
      of the life cycle of P. capsici and P. colocasiae. Rupture of released zoospores
      induced by stilbenes was reduced by addition of 100 mM glucose. The effects of
      stilbenes on mycelial growth and zoospore release, but not zoospore rupture, were
      reduced largely when pH value was above 7. In addition, stilbenes were
      investigated for its antifungal stability against Phytophthora sp. The results
      showed that stilbenes maintained strong fungistatic activity over a wide pH range
      (pH 4-9) and temperature range (70-120  degrees C). The compound stilbenes
      exhibited strong and stable broad-spectrum antifungal activity, and had a
      significant fungicidal effect on fungal cells. Results from prebiocontrol
      evaluations performed to date are probably useful in the search for alternative
      approaches to controlling serious plant pathogens.

PMID- 24122629
TI  - An evaluation of the proteolytic and lipolytic potential of Penicillium spp.
      isolated from traditional Greek sausages in submerged fermentation.
AB  - A number of novel Penicillium strains belonging to Penicillium nalgiovense,
      Penicillium solitum, Penicillium commune, Penicillium olsonii, and Penicillium
      oxalicum species, isolated from the surface of traditional Greek sausages, were
      evaluated for their proteolytic and lipolytic potential in a solid substrate
      first and next in submerged fermentations, using complex media. Extracellular
      proteolytic activity was assessed at acid, neutral, and alkaline pH, while the
      lipolytic activity was assessed using olive oil, the short-chain triacylglycerol
      tributyrin, and the long-chain triolein, as substrates. The study revealed that
      although closely related, the tested strains produce enzymes of distinct
      specificities. P. nalgiovense PNA9 produced the highest alkaline proteolytic
      activity (13.2 unit (U)/ml) and the highest lipolytic activity with tributyrin
      (92 U/ml). Comparisons with known sources show that proteases and/or lipases can
      be secreted effectively by some Penicillia (P. nalgiovense PNA4, PNA7, and PNA9
      and P. solitum PSO1), and further investigations on their properties and
      characteristics would be promising.

PMID- 24122630
TI  - Detoxifying CO2 capture reclaimer waste by anaerobic digestion.
AB  - The decrease in toxicity of carbon capture reclaimer monoethanolamine (MEA) waste
      (MEAw) during anaerobic degradation of such waste together with easily degradable
      organics was investigated. Samples were collected from a bioreactor at steady
      state with 86 % organic chemical oxygen demand removal at room temperature, which
      had been running on MEAw for 2 years. The toxicity of the digester effluents were
      126, 42 and 10 times lower than that of the MEAw to the tested freshwater trophic
      groups of Pseudokirchneriella subcapitata, Daphnia magna and embryos of Danio
      rerio, respectively. The toxicity of the tested taxonomic groups after anaerobic
      digestion was mainly attributed to the ammonia generated by the degradation of
      MEAw.

PMID- 24122631
TI  - High miR-21 expression from FFPE tissues is associated with poor survival and
      response to adjuvant chemotherapy in colon cancer.
AB  - Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are
      needed to identify CC patients at high risk of recurrence and those who may
      benefit from therapeutic intervention. The aim of this study is to investigate if
      miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE)
      tissue sections is associated with prognosis and therapeutic outcome for patients
      with CC. The expression of miR-21 was measured by quantitative reverse
      transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n =
      156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors
      was associated with poor survival in both the stage II/III Japanese (p = 0.0008)
      and stage II German (p = 0.047) cohorts. These associations were independent of
      other clinical covariates in multivariable models. Receipt of adjuvant
      chemotherapy was not beneficial in patients with high miR-21 in either cohort. In
      the Japanese cohort, high miR-21 expression was significantly associated with
      poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with
      improved survival in patients with low miR-21 (p = 0.001). These results suggest
      that miR-21 is a promising biomarker to identify patients with poor prognosis and
      can be accurately measured in FFPE tissues. The expression of miR-21 may also
      identify patients who will benefit from adjuvant chemotherapy. 

PMID- 24122632
TI  - Induction of adhesion molecule expression in co-culture of human bronchial
      epithelial cells and neutrophils suppressed by puerarin via down-regulating p38
      mitogen-activated protein kinase and nuclear factor kappaB pathways.
AB  - OBJECTIVE: In this study, we aimed to investigate the expressions of adhesion
      molecules on human bronchial epithelial cells and neutrophils in co-culture
      system, assess the effects of puerarin on suppressing these adhesion molecules
      expressions, and explore the roles of two crucial signal-transduction elements
      p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NF
      kappaB) in modulating adhesion molecules expressions. METHODS: Neutrophils and
      BEAS-2B cells (one human bronchial epithelial cell line) were co-cultured, and
      adhesion molecules expressions on cell surface were detected using flow
      cytometry. The mRNA levels of adhesion molecules were assessed by real-time
      quantitative polymerase chain reaction (real-time qPCR). Phosphorylated p38 MAPK
      and inhibitor kappaB were analyzed by Western blot. RESULTS: In co-culture
      system, adhesion molecules expressions on BEAS-2B cells and neutrophils were
      enhanced significantly (P<0.05). Correspondingly, the mRNA levels of adhesion
      molecules were also increased greatly. Moreover, the pretreatment of peurarin
      obviously suppressed adhesion molecules expressions on cell surface. Furthermore,
      phosphorylated p38 MAPK and inhibitor kappaB in BEAS-2B cells and neutrophils
      were elevated in co-culture system, but decreased significantly after upon the
      treatment of peurarin (P<0.05). CONCLUSIONS: Coculture boosted the interactions
      between human bronchial epithelial cells and neutrophils mimicking airway
      inflflammation, whereas peurarin decreased the expression of adhesion molecules
      on cell surface by suppressing the activities of p38 MAPK and NF-kappaB pathways,
      and exhibiting its anti-inflflammation activity.

PMID- 24122633
TI  - New era of left main coronary artery treatment strategy.
AB  - For several decades of medical history, coronary-artery bypass grafting (CABG)
      has been regarded as the best treatment option for patients with unprotected left
      main coronary artery (LMCA) disease, considering lesion priority and its clinical
      consequences. Over the time, with remarkable advancements in techniques of
      percutaneous coronary intervention (PCI), supporting devices, and adjunctive
      pharmacologic therapy, PCI with DES implantation has appeared to be new and
      alternative option for optimal revascularization therapy for these patients. The
      available cumulative evidence suggests that the safety outcomes such as mortality
      or composite of death, myocardial infarction and stroke are similar among PCI and
      CABG for patients with LMCA disease, the only difference was the rate of repeat
      revascularization. Current evidence and ongoing large clinical trials may
      encourage interventional cardiologists to choose PCI with stenting as an
      alternative revascularization strategy for unprotected LMCA disease in future.
      Finally, this evidence will change the current clinical practice and the
      guideline of optimal revascularization strategy for unprotected LMCA disease. 

PMID- 24122634
TI  - Catheter closure of atrial septal defect in patients with cryptogenic stroke:
      initial experience in Japan.
AB  - A recent study has shown that cryptogenic stroke can occur even in patients with
      small or insignificant atrial septal defects (ASD). However, clinical experience
      in this field is still limited in Japan, also the efficacy and safety of catheter
      closure of such defects have not been identified. To evaluate the efficacy and
      safety of catheter closure of interatrial communication in patients with
      cryptogenic stroke, 13 patients who were diagnosed with cerebrovascular events
      due to cryptogenic embolism were included in this study. Mean age at procedure
      was 43 +/- 15 (range 17-68) years. In all patients, the presence of spontaneous
      or provoked interatrial right-to-left shunts was demonstrated by transesophageal
      contrast echocardiography. Mean defect size evaluated by the balloon sizing
      technique was 9.2 +/- 2.8 mm, and mean size of the Amplatzer Septal Occluder
      deployed was 9.5 +/- 2.8 mm. Devices were successfully deployed in all patients,
      though one device migrated into the descending aorta was retrieved by a snare
      catheter. Complete closure was detected by transesophageal contrast
      echocardiography at 12 months after the procedure was in 11 (85%) of the 13
      patients. During the follow-up period (30.1 +/- 9.4 months), no recurrent
      thromboembolic event was observed. Catheter closure of interatrial right-to-left
      communications can be safely performed. This procedure may contribute to
      reduction or prevention of recurrent neurological events in this patient
      population.

PMID- 24122635
TI  - Effect of postconditioning in patients with ST-elevation acute myocardial
      infarction.
AB  - Postconditioning (PosC), which is a brief period of ischemia performed at the
      time of reperfusion therapy, reduces the infarct size in animal models. We aim to
      evaluate the impact of PosC in patients with ST-elevation acute myocardial
      infarction (STEMI). Between January 2008 and August 2009, 37 STEMI patients
      received PosC. The control group comprised 42 age- and sex-matched patients
      diagnosed with STEMI in 2007-2008. In the PosC group, we applied four cycles of
      30-s balloon inflation and 30-s balloon deflation within 3 min after
      thrombectomy, and implanted the stent after PosC. In the control group, we
      directly implanted the stent after thrombectomy. The number of patients with
      myocardial blush grade 2 or 3 after the procedure was higher in the PosC group
      than in the control group (65 vs. 43%, p = 0.04). The ST-segment resolution >50%
      was greater in the PosC group compared to the control group (81 vs. 57%, p =
      0.02). Serial changes of creatine kinase and creatine kinase myocardial fraction
      after reperfusion were significantly lower in the PosC group than in the control
      group. In conclusion, PosC is a safe and feasible strategy that might preserve
      myocardial perfusion and reduce the infarct size in patients with STEMI.

PMID- 24122636
TI  - Efficacy of metal tip catheter for chronic total occlusion lesions in peripheral
      arterial disease.
AB  - We performed several techniques for chronic total occlusion (CTO) lesions in
      peripheral arterial disease (PAD). We evaluated the cases using the metal tip
      catheter (MT). We performed peripheral endovascular therapy (EVT) using MT in 31
      cases 32 lesions of PAD from March 2007 to March 2011. Twenty-nine cases were CTO
      lesions using MT for back up of guidewire or MT alone in order to penetrate like
      a bougie with the blunt tip of MT. Two cases were acute arterial thrombosis for
      thrombectomy. Seven cases were CTO of the iliac artery (IA) and 25 cases were of
      the femoral artery (FA). Seven cases were in-stent restenosis. All 7 cases of IA
      were successfully treated with the initial techniques. We were unable to
      penetrate by MT(MT-) in 7 cases of FA, and in 2 cases out of the 7, we were even
      unable to cross the guidewire. Mean lesion length was 80 +/- 42 mm in IA and 188
      +/- 88 mm in SFA. Among them, MT- was 164 +/- 67 mm with no significant
      differences. Procedure time of EVT for CTO using MT was significantly shorter
      than other strategies. We had no complications such as perforation by using MT.
      MT provides high initial success rate by spectacular penetration performance and
      pushability. MT is a safe and effective device for CTO in PAD.

PMID- 24122637
TI  - Favorable pharmacokinetics of biolimus A9 after deployment of Nobori stent for
      coronary artery disease: insights from Nobori PK study in Japanese subjects.
AB  - The Nobori stent is a new drug-eluting stent (DES) with biodegradable polymer
      coating limited to the abluminal side of stents. Biolimus A9 is a novel sirolimus
      derivative specifically developed for DES, and polymer load 15.6 MUg of biolimus
      A9 per 1 mm of stent. A non-randomized multicenter trial was conducted in Japan.
      Twenty-two de novo lesions were treated by Nobori stents and biolimus A9
      concentration in whole blood was serially measured at 14 predetermined time
      points using a validated chromatography-tandem mass spectrometry (LC-MS/MS)
      assay. The C max was 85.3 +/- 37.9 pg/mL (min-max 46.7-169 pg/mL) in the 18 mm
      cohort and 198 +/- 81 pg/mL (min-max 82.5-365 pg/mL) in the >= 28 mm cohort and
      no early or late bursts of biolimus A9 release were documented. After 4 weeks, no
      measurable concentration of biolimus A9 was observed in any patient. Estimated
      AUC0-t was 1.12 +/- 1.16 ng/mL h in the 18 mm group, and 5.93 +/- 4.41 ng/mL h
      for the >= 28 mm group. A significant association between loaded biolimus A9 dose
      adjusted by patient weight and pharmacokinetic parameters was observed. The
      systemic exposure of biolimus A9 eluting from the Nobori stent was low and
      proportional to the loaded amount of biolimus A9, and clearance from the blood
      was rapid. These findings suggest that the Nobori stent is feasible and safe.
      Systemic lower exposure of biolimus A9 after Nobori stent implantation may have
      beneficial effects on stent endothelialization.

PMID- 24122638
TI  - Intravascular ultrasound-guided percutaneous coronary intervention for total
      occlusion of the proximal left anterior descending artery caused by spontaneous
      coronary dissection in a young woman.
AB  - A 35-year-old woman was admitted to our hospital because of a sudden cardiac
      arrest caused by an acute anterior myocardial infarction. Emergency coronary
      angiography showed total occlusion of the proximal left anterior descending
      artery (LAD). We performed an intravascular ultrasound (IVUS) to detect the LAD
      orifice and successfully inserted the guidewire to the occluded LAD. An IVUS
      revealed coronary dissection and no atheromatous plaque from the orifice to the
      mid-portion of the LAD and the guidewire was in the true lumen. Two bare metal
      stents were implanted in the proximal and mid portion of the LAD. After stenting
      to the LAD, coronary dissection retrogradely extended to the left circumflex
      artery (LCx). Therefore, we performed additional stent implantation from the left
      main trunk (LMT) to the proximal LCx and the just proximal LAD. An IVUS guided
      percutaneous coronary intervention (PCI) enabled complete revascularization to
      spontaneous coronary artery dissection. 

PMID- 24122640
TI  - Contrast media injection into right coronary artery caused thrombus extraction to
      aorta that may have resulted in left main trunk thrombosis.
AB  - A 59-year-old man with inferior acute myocardial infarction underwent an urgent
      coronary angiography and as a result a total occlusion of the ostial right
      coronary artery (RCA) was observed. Interestingly, the thrombus in the RCA
      clearly shortened within 2.3 s during the contrast media injection. While we
      prepared for percutaneous coronary intervention (PCI) of the RCA, ventricular
      fibrillation occurred and pulseless electrical activity continued in spite of
      repeated cardioversion. Despite no stenosis in the left main trunk (LMT) in the
      initial coronary angiography, the LMT was totally occluded. Following aspiration
      therapy on the LMT with percutaneous cardiopulmonary support, PCI of the RCA was
      performed. A coronary angiography should be carefully performed if a lot of
      thrombi exist in the coronary ostium because LMT embolism may have been caused by
      thrombus extraction from the RCA by contrast media injection.

PMID- 24122641
TI  - Acute coronary occlusion by injured aortic valve during percutaneous coronary
      intervention.
AB  - We report a rare case of a 58-year-old male with accidental occlusion of left
      main trunk (LMT) artery by injured aortic valve during percutaneous coronary
      intervention (PCI). Although we successfully bailed out this complication by
      urgent LMT stenting, aortic regurgitation developed immediately after PCI.
      Echocardiography detected a filamentous structure attached to the aortic valve.
      An elective aortic valve replacement surgery revealed that his right coronary
      cusp was torn into two filamentous strips. One strip accidentally plunged into
      LMT and was fixed by the intracoronary stent. Another strip floated in the aortic
      root and appeared as though vegetation attached to the aortic valve in case of
      acute infective endocarditis. Guiding catheters probably injured the aortic valve
      during PCI. This report reminded us of the importance of meticulous manipulation
      of a guiding catheter. 

PMID- 24122642
TI  - Culprit segments identified by optical coherence tomography in patients with
      acute myocardial infarction: two case reports.
AB  - The high resolution of optical coherence tomography (OCT) provides detailed
      information about coronary plaque morphology, which enables the mechanism of
      acute myocardial infarction to be evaluated. We describe two patients with acute
      myocardial infarction in whom culprit segments were identified by OCT, but not by
      either coronary angiography or intravascular ultrasound. 

PMID- 24122643
TI  - Novel strategy for percutaneous transluminal angioplasty for complex critical
      hand.
AB  - A 60-year-old patient with end-stage renal disease was referred to our institute
      with ischemic tissue loss and pain at rest of the fourth finger of the left hand.
      Lesions involved the subclavian artery, the brachial artery, the ulnar artery,
      the radial artery and the palmer arch. After successful angioplasty with noble
      technique, patient's symptoms were disappeared immediately and ischemic lesions
      were healed at only 1-month follow-up. This interesting case report may
      illustrate a help of treatment strategy of critical hand ischemia with complex
      lesions. 

PMID- 24122644
TI  - Staged interventional management of a massive thrombus related to coronary artery
      ectasia in acute coronary syndrome.
AB  - Coronary artery ectasia (CAE), which is reported in 0.3-5.3% of coronary
      angiograms, is known as a risk factor of acute coronary syndrome (ACS). Optimal
      treatment of CAE in ACS has not yet been established because of few clinical
      reports and no randomized trial. We describe a 78-year-old woman in whom
      thrombolysis with recombinant tissue-plasminogen activator, heparin and dual
      antiplatelet therapy were performed, and an angiogram after 3 days revealed the
      disappearance of massive thrombus in the CAE of the left circumflex coronary
      artery. Staged percutaneous coronary intervention and multidisciplinary procedure
      are feasible to treat ACS with massive thrombus.

PMID- 24122645
TI  - An analysis of entorhinal cortex projections to the dentate gyrus, hippocampus,
      and subiculum of the neonatal macaque monkey.
AB  - The entorhinal cortex is the primary interface between the hippocampal formation
      and neocortical sources of sensory information. Although much is known about the
      cells of origin, termination patterns, and topography of the entorhinal
      projections to other fields of the adult hippocampal formation, very little is
      known about the development of these pathways, particularly in the human or
      nonhuman primate. We have carried out experiments in which the anterograde
      tracers (3) H-amino acids, biotinylated dextran amine, and Phaseolus vulgaris
      leucoagglutinin were injected into the entorhinal cortex in 2-week-old rhesus
      monkeys (Macaca mulatta). We found that the three fiber bundles originating from
      the entorhinal cortex (the perforant path, the alvear pathway, and the
      commissural connection) are all established by 2 weeks of age. Fundamental
      features of the laminar and topographic distribution of these pathways are also
      similar to those in adults. There is evidence, however, that some of these
      projections may be more extensive in the neonate than in the mature brain. The
      homotopic commissural projections from the entorhinal cortex, for example,
      originate from a larger region within the entorhinal cortex and terminate much
      more densely in layer I of the contralateral entorhinal cortex than in the adult.
      These findings indicate that the overall topographical organization of the main
      cortical afferent pathways to the dentate gyrus and hippocampus are established
      by birth. These findings add to the growing body of literature on the development
      of the primate hippocampal formation and will facilitate further investigations
      on the development of episodic memory.

PMID- 24122646
TI  - Berry antioxidants: small fruits providing large benefits.
AB  - Small berry fruits are consumed because of their attractive colour and special
      taste, and are considered one of the richest sources of natural antioxidants.
      Their consumption has been linked to the prevention of some chronic and
      degenerative diseases. The term 'berry fruits' encompasses the so-called 'soft
      fruits', primarily strawberry, currants, gooseberry, blackberry, raspberry,
      blueberry and cranberry. The objective of this review is to highlight the
      nutraceutical value of berries and to summarize the factors affecting berry fruit
      antioxidants. Particular attention is given to postharvest and processing
      operation factors that may affect fruit phytochemical content. The structure
      antioxidant relationships for phenolic compounds - the main group of antioxidants
      in this fruit group - are presented and major areas for future research are
      identified.

PMID- 24122647
TI  - A sex difference in the onset of the latent learning impairment in rats.
AB  - The current study examined a sex difference in the onset of a latent learning
      impairment in Sprague-Dawley rats. Forty rats (20 male, 20 female) were tested on
      the Latent Cue Preference (LCP) task at 3 or 11 months of age. Additionally, 19
      female rats were tested at 14 or 18 months of age. All rats were given four
      training trials in the LCP task using a three-compartment box, during which the
      rats explored a water-paired compartment and an unpaired compartment (each with a
      different visual cue) on consecutive days. Rats were then water-deprived for 23
      hr and given a compartment preference test, in which more time spent in the water
      paired compartment demonstrated latent learning. Results showed that 11-month old
      males and 18-month old females showed impaired latent learning, but 11- and 14
      month old females showed intact latent learning, which may possibly be due to the
      neuroprotective effects of estrogen.

PMID- 24122648
TI  - Spectroscopic studies of the unfolding of a multimeric protein alpha-crystallin.
AB  - alpha-Crystallin is a multimeric eye lens protein having molecular chaperone-like
      function which is crucial for lens transparency. The stability and unfolding
      refolding properties of alpha-crystallin plays important roles for its function.
      We undertook a multi probe based fluorescence spectroscopic approach to explore
      the changes in the various levels of organization of this protein at different
      urea concentration. Steady state fluorescence studies reveal that at 0.6M urea a
      compact structural intermediate is formed which has a native-like secondary
      structure with enhanced surface exposure of hydrophobic groups. At 2.8M urea the
      tertiary interactions are largely collapsed with partial collapse of secondary
      and quaternary structure. The surface solvation probed by picosecond time
      resolved fluorescence of acrylodan labeled alpha-crystallin revealed dry native
      like core of alpha-crystallin at 0.6M urea compared to enhanced water penetration
      at 2.8M urea and extensive solvation at 6M urea. Activation energy for the
      subunit exchange decreased by 22 kJ mol(-1) on changing urea concentration from 0
      to 0.6M compared with over 75 kJ mol(-1) on changing urea concentration from 0 to
      2.8M. Light scattering and analytical ultracentrifugation techniques were used to
      determine size and oligomerization of the unfolding intermediates. The data
      indicated swelling but no oligomer breakdown at 0.6M urea. At 2.8M urea the
      oligomeric size is considerably reduced and a monomer is produced at 6M urea. The
      data clearly reveals that structural breakdown of alpha-crystallin does not
      follow hierarchical sequence as tertiary structure dissolution takes place before
      complete oligomeric dissociation.

PMID- 24122649
TI  - Evaluation of sexual behavior of housed male camels (Camelus dromedarius) through
      female parades: correlation with climatic parameters.
AB  - Camels are seasonal breeders, and their sexual behavior is influenced by
      environmental conditions, but the relationship between climatic factors and
      sexual behavior has been poorly described in the available literature. Nowadays,
      the male camel living habit is shifting towards captivity; thus, this study was
      carried out to evaluate the sexual behavior of housed male dromedary camel
      through female's parades and to correlate it with climatic parameters. Four
      housed sires, reared for semen collection, and one dam were used and the trial
      lasted 8 weeks, considering the first week as control. Six days per week and
      during evenings, the female was brought near each males' boxes, while two
      observers filled a behavioral sampling ethogram and scored the male sexual
      behavior. After this parade, blood samples were taken from the female to evaluate
      the estradiol concentration. In addition, the following meteorological parameters
      were recorded, everyday, at 9:00 a.m. and 19:00 p.m.: pressure, wind,
      temperature, humidity, and H-index. The correlation between sexual behavioral
      score and female estradiol concentration and climate parameters was analyzed. All
      the behavioral parameters showed a significant upward trend; female estradiol
      concentration varied during the period and picked at week 5. Male sexual behavior
      was negatively correlated with morning H-index, wind, and temperature, and
      positively correlated with pressure and evening humidity, whereas it was not
      correlated with estrogen. In conclusion, female parade was a successful method to
      evaluate and stimulate the occurrence of housed male dromedary camel sexual
      activity that resulted to be negatively affected by hot temperature, warm wind,
      and lack of rain.

PMID- 24122650
TI  - A Synthesis of Peer-Mediated Academic Interventions for Secondary Struggling
      Learners.
AB  - A synthesis of the extant research on peer-mediated reading and math
      interventions for students in regular or alternative education settings with
      academic difficulties and disabilities in Grades 6 to 12 (ages 11-18) is
      presented. Interventions conducted between 2001 and 2012 targeting reading and
      math were included if they measured effects on at least one academic outcome
      measure. A total of 13 intervention studies were synthesized in which 10 studies
      employed an experimental or quasi-experimental design and three studies used a
      single-case design. Findings from the 13 studies revealed mostly moderate to high
      effects favoring peer mediation, particularly when implementing a peer-mediated
      feedback component. In addition, findings suggest such interventions have social
      validity among adolescents and teachers. More rigorous research on secondary peer
      mediated math interventions, peer-mediated interventions in alternative settings,
      and effective ways to pair dyads to incorporate a structured feedback component
      is warranted. Implications for peer-mediated instruction for academically
      struggling adolescents are discussed. 

PMID- 24122651
TI  - Trehalose and sorbitol alter the kinetic pattern of inactivation of glutamate
      dehydrogenase during drying in levitated microdroplets.
AB  - A single-droplet acoustic levitator was used to determine the drying rate and the
      kinetics of inactivation of glutamate dehydrogenase in the presence of added
      trehalose or sorbitol. The solution was also spray dried under the same process
      condition of drying gas temperature on a bench-top machine. Both trehalose and
      sorbitol delay the point of onset of enzyme inactivation which lies after the
      critical point of drying. Both carbohydrates also reduce the apparent rate
      constant of inactivation calculated during the subsequent inactivation phase. The
      carbohydrates stabilise, therefore, the enzyme during droplet drying and particle
      formation mainly during the falling rate drying period. There is no difference
      between the stabilising effects of the two carbohydrates when examined as
      levitated single droplets. This suggests the importance of water replacement as a
      stabilising mechanism in the levitated droplets/particles. On spray drying, the
      trehalose stabilises the enzyme better than does the sorbitol at a drying gas
      (outlet) temperature of 60 degrees C. This suggests glass formation with the
      trehalose but not the sorbitol during the very rapid drying process of small
      atomised droplets in the spray dryer.

PMID- 24122652
TI  - Deceleration-stats save much time during phototrophic culture optimization.
AB  - In case of phototrophic cultures, photobioreactor costs contribute significantly
      to the total operating costs. Therefore one of the most important parameters to
      be determined is the maximum biomass production rate, if biomass or a biomass
      associated product is the desired product. This is traditionally determined in
      time consuming series of chemostat cultivations. The goal of this work is to
      assess the experimental time that can be saved by applying the deceleration stat
      (D-stat) technique to assess the maximum biomass production rate of a
      phototrophic cultivation system, instead of a series of chemostat cultures. A
      mathematical model developed by Geider and co-workers was adapted in order to
      describe the rate of photosynthesis as a function of the local light intensity.
      This is essential for the accurate description of biomass productivity in
      phototrophic cultures. The presented simulations demonstrate that D-stat
      experiments executed in the absence of pseudo steady-state (i.e., the arbitrary
      situation that the observed specific growth rate deviates <5% from the dilution
      rate) can still be used to accurately determine the maximum biomass productivity
      of the system. Moreover, this approach saves up to 94% of the time required to
      perform a series of chemostat experiments that has the same accuracy. In case
      more information on the properties of the system is required, the reduction in
      experimental time is reduced but still significant.

PMID- 24122653
TI  - Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal
      stem cell spheroids for cartilage regeneration.
AB  - Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to
      replace suspended single cells in modern cell-based therapies because of their
      greater regeneration capacities in vitro. They may lose the 3D structure during a
      change of microenvironment, which poses challenges to their translation in vivo.
      Besides, the conventional microporous scaffolds may have difficulty in
      accommodating these relatively large spheroids. Here we revealed a novel design
      of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable
      scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids
      were made by solid freeform fabrication (SFF) from the solution of poly(D,L
      lactide-co-glycolide). Their internal surface was modified with chitosan
      following air plasma treatment in order to preserve the morphology of the
      spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds
      produced a significantly larger amount of cartilage-associated extracellular
      matrix in vitro and in NOD/SCID mice compared to single cells in the same
      scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral
      defects of rabbit knees showed superior cartilage regeneration. This study
      establishes new perspectives in designing the spheroid-sustaining
      microenvironment within a tissue engineering scaffold for in vivo applications. 

PMID- 24122654
TI  - MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of
      large bone defects.
AB  - The functional repair of large skeletal defects remains a significant challenge
      to orthopaedic surgeons due to the lack of effective strategies to promote bone
      regeneration, particularly in the elderly. This study investigated the potential
      use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen
      scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair
      a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4
      month-old donor mice were seeded in type I collagen gels that were then
      compressed to form scaffolds with a fibrillar density similar to osteoid. The
      cells remained metabolically active in scaffolds incubated in vitro for up to 15
      days and differentiated into osteoblasts that deposited calcium-phosphate mineral
      into the scaffold, which was quantified using micro-computed tomographic (micro
      CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded
      scaffolds were rapidly mineralised and integrated into host bone with
      administration of 10 ng of recombinant VEGF injected into the femoral canal at 4
      days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects
      that did not receive a bolus dose of VEGF did not mineralise or integrate with
      native bone. The approach with MSC, hydrogels and a biologic factor already
      approved for human use warrants further pre-clinical investigation with a large
      animal model. 

PMID- 24122656
TI  - Possible participation of acidic pH in bone resorption in middle ear
      cholesteatoma.
AB  - OBJECTIVES/HYPOTHESIS: The etiopathology of bone resorption in cholesteatoma is
      unclear. We studied pH in middle ear cholesteatoma tissue and the permeability of
      the cholesteatoma epithelium in an attempt to elucidate the mechanism of bone
      resorption in this disease. STUDY DESIGN: Laboratorial study. METHODS:
      Cholesteatoma tissue was collected from patients with primary acquired middle ear
      cholesteatoma. The pH of the keratin debris of cholesteatoma was measured using a
      pH meter. The cholesteatoma epithelium was examined under a confocal laser
      scanning microscope, and under a transmission electron microscope. Expression of
      filaggrin in the cholesteatoma tissue was explored by fluorescence
      immunohistochemistry and by quantitative reverse transcription-polymerase chain
      reaction. RESULTS: The pH of the keratin debris of cholesteatoma was acidic. The
      pH of the basal layer of the cholesteatoma epithelium was significantly lower
      than that of the antrum mucosa. Transmission electron microscope showed distinct
      penetration of lanthanum in the intercellular space of the basal, spinous, and
      granular layers of the cholesteatoma epithelium, but only a small amount of
      lanthanum in the granular layer in the normal skin. The expression of filaggrin
      mRNA was significantly lower in the cholesteatoma tissue than in the normal skin.
      CONCLUSIONS: These results indicate that acid leakage through the cholesteatoma
      epithelium probably participates in the resorption of the underlying bone
      structure. The increased permeability of the cholesteatoma epithelium may be
      explained by a decrease in filaggrin expression.

PMID- 24122657
TI  - Preventing pharyngo-cutaneous fistula in total laryngectomy: a systematic review
      and meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: Concurrent chemoradiotherapy is the gold-standard
      nonsurgical organ-preservation treatment for advanced laryngeal carcinoma. Total
      laryngectomy (TL) is increasingly reserved for surgical salvage. Salvage surgery
      is associated with more complications than primary surgery. A systematic review
      and meta-analysis was undertaken to establish the impact of organ preservation
      protocols on pharyngo-cutaneous fistula incidence following TL, and to synthesize
      evidence on the role of "onlay" prophylactic tissue flaps in reducing this
      complication in salvage TL. DATA SOURCES: The English language literature
      (January 1, 2000, to September 1, 2013) was searched, using PUBMED and EMBASE
      databases, for the terms "laryngectomy" and "fistula." Of 522 studies identified
      from database searches, 33 were included in the quantitative synthesis. REVIEW
      METHODS: Studies reporting fistula incidence following primary TL (PTL), salvage
      TL (STL), and STL with "onlay" flap-reinforced pharyngeal closure were included.
      Data were extracted by the first author (M.S.). Meta-analysis of fistula
      incidence was performed. RESULTS: PTL fistula incidence is 14.3% (95% CI 11.7
      17.0), STL 27.6% (23.4-31.8), and STL with flap-reinforced closure 10.3% (4.6
      15.9). Chemoradiotherapy is associated with a pooled fistula incidence of 34.1%
      (22.6-45.6), compared to 22.8% (18.3-27.4) for radiotherapy alone. Relative risk
      of fistula is 0.566 (0.374-0.856, P = 0.001) for STL with flap-reinforced closure
      compared to STL alone. The number needed to treat (NNT) to prevent one fistula is
      6.05. CONCLUSION: Prophylactic flaps used in an "onlay" technique reduce fistula
      incidence in STL. Chemoradiotherapy increases fistula incidence more than
      radiotherapy alone. Prophylactic flaps should be offered in salvage cases after
      failed chemoradiation protocols.

PMID- 24122658
TI  - Understanding disposition after referral for bariatric surgery: when and why
      patients referred do not undergo surgery.
AB  - BACKGROUND: Bariatric surgery is an effective long-term solution for weight loss
      in the severely obese. Prevalence of bariatric surgery has increased over the
      recent years; however, the attrition rate of those referred who actually undergo
      surgery is high. The purpose of this study was to examine patients' attrition
      rates after referral for bariatric surgery at an academic tertiary care
      institution. When and why patients who were referred for bariatric surgery did
      not ultimately undergo surgical treatment was examined. METHODS: Charts of 1,237
      patients referred to the Toronto Western Hospital Bariatric Program from program
      inception to February 2011 were retrospectively reviewed. Patient demographics,
      appointment dates, no shows and cancellations, and when and why patients did not
      undergo surgery were summarized. RESULTS: Patients' mean age was 47. Most
      patients were female, and the mean body mass index was 47. Half (50.6 %) of the
      total persons referred left the program prior to being seen by a health-care
      professional, and only 36.2 % underwent surgical treatment. Only 2.75 % of
      persons were ineligible for surgery. A total of 60.6 % of persons self-removed
      from our program. Reasons for self-removal varied, with the most common reason
      for leaving the program recorded as "unknown." CONCLUSIONS: Our multidisciplinary
      program with in-hospital psychosocial resources resulted in very few persons
      being excluded from receiving surgical treatment. However, less than half of
      those referred underwent surgery as most persons self-removed from our program
      for unknown reasons. Further investigation is required to determine which
      patient, administrative, and system factors play a role in the patients' decision
      to not undergo bariatric surgical treatment.

PMID- 24122659
TI  - The relationship of pre-operative health status to sustained outcome in gastric
      bypass surgery.
AB  - The task of sustaining initial weight loss after gastric bypass surgery has been
      identified as the area of greatest concern in this intervention. The present
      study investigated the role of good vs. poor pre-operative health as a moderator
      variable in identifying useful pre-operative predictors of continued weight loss.
      Follow-up data at a mean of 12.8 months and again at 3.2 years post-operatively
      were available for 79 patients on 227 interview variables and four psychological
      assessment instruments. These measures were studied for their success in
      predicting continued weight loss over the 1-3-year period separately for patients
      who were in good and in poor general pre-operative health. Previous findings
      showed that the overall mean simple weight loss to 12.8 months was 45.61 kg, but
      additional weight loss to 3.2 years was only 0.28 kg. The good and poor pre
      operative health groups differed little on these figures. However, the
      significant predictors of continued weight loss for good-health patients (high
      anxiety and distress, low self-esteem, poor eating habits, strong expectations of
      life improvement, and good achievement and coping skills) were quite different
      from those for poor-health patients (good psychological health and happiness,
      strong personal support and life satisfaction, good eating habits, and little
      knowledge about their health). Thus, pre-operative health status served as a
      powerful moderator in predicting continued weight loss from pre-operative
      characteristics. These findings offer a means of making more accurate predictions
      as to which patients are the best candidates for surgery, and also suggest that
      different psychological and other interventions should be selected according to
      pre-operative health status.

PMID- 24122660
TI  - Patients' perspectives on laparoscopic adjustable gastric banding (LAGB)
      aftercare attendance: qualitative assessment.
AB  - BACKGROUND: Despite recognition of the importance of laparoscopic adjustable
      gastric banding (LAGB) aftercare for optimal surgical outcomes and the failure of
      some patients to attend regularly, factors influencing LAGB aftercare attrition
      have not been thoroughly examined in the literature. METHODS: Patients'
      perspectives on LAGB aftercare attendance were explored using a qualitative
      research methodology. Twenty-four LAGB patients who either (1) did not attend
      aftercare (n = 12) or (2) attended aftercare regularly (n = 12) were interviewed.
      Data were analysed using grounded theory methods. RESULTS: Four common processes
      emerged from patients' descriptions: (1) barriers to attendance, (2) purely
      medical service, (3) non-patient centred approach, and (4) behavioural and
      psychological aspects of behavioural changes. Regular attendees typically
      reported (1) a commitment to aftercare, (2) a need to make the band work, (3)
      regular monitoring motivated attendance, and (4) happiness with the improved
      health. Non-regular attendees perceived (1) that aftercare is more relevant early
      on after the surgery, (2) insufficient follow-up from the centre, (3) failure and
      shame, (4) not comfortable to be vulnerable, and (5) an intention to reconnect.
      CONCLUSIONS: Patients perceive LAGB post-operative medical management to be
      professional, effective, and valuable. Patients' difficulty to actively
      participate during aftercare visits contributes to reduced satisfaction and a
      range of compromised outcomes. Management of LAGB post-operative patients may be
      improved with the use of patient-centred strategies that encourage patients'
      active participation. Further research is required to evaluate the emerged themes
      and determine whether interventions targeting identified barriers enhance
      attendance and improve outcomes.

PMID- 24122661
TI  - Comparison of nutritional status during the first year after sleeve gastrectomy
      and Roux-en-Y gastric bypass.
AB  - Sleeve gastrectomy (SG) is supposed to induce fewer nutritional deficiencies than
      gastric bypass (GBP). However, few studies have compared nutritional status after
      these two procedures, and the difference in weight loss (WL) between procedures
      may alter the results. Thus, our aim was to compare nutritional status after SG
      and GBP in subjects matched for postoperative weight. Forty-three subjects who
      underwent SG were matched for age, gender, and 6-month postoperative weight with
      43 subjects who underwent GBP. Dietary intakes (DI), metabolic (MP), and
      nutritional parameters (NP) were recorded before and at 6 and 12 months after
      both procedures. Multivitamin supplements were systematically prescribed after
      surgery. Before surgery, BMI, DI, MP, and NP were similar between both groups.
      After surgery, LDL cholesterol, serum prealbumin, vitamin B12, urinary calcium,
      and vitamin D concentrations were lower after GBP than after SG, whereas WL and
      DI were similar after both procedures. However, the total number of deficiencies
      did not increase after surgery regardless of the procedure. In addition, we found
      a significant increase in liver enzymes and a greater decrease in C-reactive
      protein after GBP. In conclusion, during the first year after surgery, in
      patients with the same WL and following the same strategy of vitamin
      supplementation, global nutritional status was only slightly impaired after SG
      and GBP. However, some nutritional parameters were specifically altered after
      GBP, which could be related to malabsorption or other mechanisms, such as
      alterations in liver metabolism.

PMID- 24122662
TI  - Involvement of autophagy in cervical, endometrial and ovarian cancer.
AB  - Autophagy is an intracellular molecular pathway that maintains cellular
      homeostasis. A role for autophagy in the development as well as in the treatment
      of gynecologic malignancies, while still under-investigated, is receiving
      increased interest. Depending on concomitant factors, autophagy can either
      promote or suppress development of cervical, endometrial and ovarian cancer.
      Moreover, these cancer cells can utilize autophagy to promote its resistance to
      chemotherapeutic agents or, conversely, autophagy can enhance the efficacy of
      cytotoxic agents by promoting autophagic cell death. In this review the key
      autophagy-related mechanisms in development and treatment of cervical,
      endometrial and ovarian cancer are elucidated and evaluated. 

PMID- 24122663
TI  - Early development of immune reconstitution inflammatory syndrome related to
      Pneumocystis pneumonia after antiretroviral therapy.
AB  - Immune reconstitution inflammatory syndrome is a recognized complication after
      the initiation of combination antiretroviral therapy (cART). We report a patient
      who developed life-threatening pulmonary immune reconstitution inflammatory
      syndrome (IRIS) three days after initiation of cART. We reviewed published cases
      of IRIS after Pneumocystis pneumonia (PCP), in particular the time from
      initiation of cART to IRIS event. The median duration from the initiation of cART
      to the onset of IRIS was 15 days in the 33 patients reviewed. This report alerts
      clinicians to the rapidity of the development of pulmonary IRIS following PCP
      after the initiation of cART.

PMID- 24122664
TI  - Extension of polyphenolics by CWPO-C peroxidase mutant containing radical-robust
      surface active site.
AB  - Expressed as insoluble forms in Escherichia coli, native cationic cell wall
      peroxidase (CWPO-C) from the poplar tree and mutant variants were successfully
      reactivated via refolding experiments and used to elucidate the previously
      presumed existence of an electron transfer (ET) pathway in the CWPO-C structure.
      Their catalytic properties were fully characterized through various analyses
      including steady-state kinetic, direct oxidation of lignin macromolecules and
      their respective stabilities during the polymerization reactions. The analysis
      results proved that the 74th residue on the CWPO-C surface plays an important
      role in catalyzing the macromolecules via supposed ET mechanism. By comparing the
      residual activities of wild-type CWPO-C and mutant 74W CWPO-C after 3 min,
      mutation of tyrosine 74 residue to tryptophan increased the radical resistance of
      peroxidase up to ten times dramatically while maintaining its capability to
      oxidize lignin macromolecules. Furthermore, extension of poly(catechin) as well
      as lignin macromolecules with CWPO-C Y74W mutant clearly showed that this radical
      resistant peroxidase mutant can increase the molecular weight of various kinds of
      polyphenolics by using surface-located active site. The anti-oxidation activity
      of the synthesized poly(catechin) was confirmed by xanthine oxidase assay. The
      elucidation of a uniquely catalytic mechanism in CWPO-C may improve the
      applicability of the peroxidase/H2O2 catalyst to green polymer chemistry.

PMID- 24122665
TI  - Synergistic growth-suppressive effects of quercetin and cisplatin on HepG2 human
      hepatocellular carcinoma cells.
AB  - Quercetin, a natural flavonoid, exhibits anticancer effects. The aim of this
      study is to determine whether the combination of quercetin with cisplatin, a
      conventional chemotherapeutic drug, would have synergistic suppressive effects on
      hepatocellular carcinoma (HCC) cells. To this end, HepG2 cells were exposed to
      quercetin (50 MUM) or cisplatin (10 MUM) alone or combination of both and cell
      proliferation and apoptosis were investigated. Our data revealed that the
      combination of quercetin and cisplatin was significantly (P < 0.05) effective in
      inducing growth suppression and apoptosis in HepG2 cells, when compared with
      single agent treatment. Quercetin combined with cisplatin modulated the
      expression of numerous genes involved in cell cycle progression and apoptosis.
      Treatment with quercetin rather than cisplatin resulted in a marked elevation of
      p16 expression in HepG2 cells. Targeted reduction of p16 using RNA interference
      technology partially reversed quercetin-induced cell cycle G1 arrest and
      apoptosis in HepG2 cells. In conclusion, quercetin has suppressive activity
      against HCC cells through p16-mediated cell cycle arrest and apoptosis and its
      combination with cisplatin yielded synergistic inhibitory effects in suppressing
      cell growth and inducing apoptosis.

PMID- 24122666
TI  - A novel approach for phosphorus recovery and no wasted sludge in enhanced
      biological phosphorus removal process with external COD addition.
AB  - In enhanced biological phosphorus removal (EBPR) process, phosphorus (P) in
      wastewater is removed via wasted sludge without actual recovery. A novel approach
      to realize phosphorus recovery with special external chemical oxygen demand (COD)
      addition in EBPR process was proposed. During the new operating approach period,
      it was found that (1) no phosphorus was detected in the effluent; (2) with an
      external addition of 10 % of influent COD amount, 79 % phosphorus in the
      wastewater influent was recovered; (3) without wasted sludge, the MLVSS
      concentration in the system increased from 2,010 to 3,400 mg/L and kept stable
      after day 11 during 24-day operating period. This demonstrates that the novel
      approach is feasible to realize phosphorus recovery with no wasted sludge
      discharge in EBPR process. Furthermore, this approach decouples P removal and
      sludge age, which may enhance the application of membrane bioreactor for P
      removal.

PMID- 24122667
TI  - Purification and characterization of NAD+ -dependent salicylaldehyde
      dehydrogenase from carbaryl-degrading Pseudomonas sp. strain C6.
AB  - NAD+-dependent salicylaldehyde dehydrogenase (SALDH) which catalyzes the
      oxidation of salicylaldehyde to salicylate was purified form carbaryl-degrading
      Pseudomonas sp. strain C6. The enzyme was found to be a functional homotrimer
      (150 kDa) with subunit molecular mass of 50 kDa and contained calcium (1.8
      mol/mol of enzyme). These properties were found to be unique. External addition
      of metal ions showed no effect on the activity and addition of chelators showed
      moderate inhibition of the activity. Potassium ions were found to enhance the
      activity significantly. SALDH showed higher affinity for salicylaldehyde (Km =
      4.5 MUM) and accepts mono- as well as di-aromatic aldehydes; however it showed
      poor activity on aliphatic aldehydes. Chloro-/nitro-substituted benzaldehydes
      were potent substrate inhibitors as compared to benzaldehyde and 3
      hydroxybenzaldehyde, while 2-naphthaldehyde and salicylaldehyde were moderate.
      The kinetic data revealed that SALDH, though having broad specificity, is more
      efficient for the oxidation of salicylaldehyde as compared to other aromatic
      aldehyde dehydrogenases which gives an advantage for Pseudomonas sp. strain C6 to
      bioremediate carbaryl and other aromatic aldehydes efficiently.

PMID- 24122669
TI  - [Efficacy and safety of antimalarial combinations for treatment of uncomplicated
      malaria in children in Bangui, Central African Republic].
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of three
      anti-malarial combinations--artemether-lumefantrine (A-L), amodiaquine
      sulfadoxine-pyrimethamine (AQ-SP), and artesunate-amodiaquine (AQ-AS)--in the
      treatment of uncomplicated malaria in children younger than 5 years in Bangui,
      Central African Republic. METHODOLOGY: This study included 186 children aged 6-59
      months with uncomplicated falciparum malaria who were treated at the Bede
      Combattant Hospital from July through October 2010: 63 randomized to receive A-L,
      63 AQ-SP, and 60 AQ-AS. Clinical outcome was classified according to WHO criteria
      as early treatment failure (ETF), late clinical failure (LCF), late
      parasitological failure (LPF), or adequate clinical and parasitological response
      (ACPR). The occurrence of mutations in the pfcrt, pfmdr-1, dhfr and dhps genes
      was studied by PCR-RFLP. RESULTS: After PCR correction, ACPR at D28 was 100% for
      A-L, 96.55% for AQ-SP, and 100% for AQ-AS, with no significant difference between
      the three combinations (p = 0.36). The 2 cases of treatment failure for AQ-SP
      were associated with mutations at the following resistance markers: Pfcrt 76T,
      PfmdrI 86Y, Dhfr 108N, and Dhps A437. There was no significant difference in the
      reduction of anemia, fever (p = 0.87), or parasitemia (p = 0.63) between the
      three combinations. CONCLUSION: This study demonstrates that artemisinin-based
      combinations are still effective and tolerated in the treatment of uncomplicated
      malaria in children younger than 5 years in Bangui. Treatment failures were due
      to new infections and mutations in resistance markers.

PMID- 24122670
TI  - Effects of high temperature after pollination on physicochemical properties of
      waxy maize flour during grain development.
AB  - BACKGROUND: Waxy maize is grown in South China, where high temperatures
      frequently prevail. The effect of high-temperature stress on grain development of
      waxy maize is not known. RESULTS: High temperature decreased the grain fresh
      weight and volume, and lowered the grain dry weight and water content after 22
      days after pollination (DAP). Plants exposed to high temperature had low starch
      content, and high protein and soluble sugar contents at maturity. Starch iodine
      binding capacity and granule size were increased by heat stress at all grain
      filling stages. The former parameter decreased, while the latter parameter
      increased gradually with grain development. High temperature increased the peak
      and breakdown viscosity before 30 DAP, but the value decreased at maturity.
      Pasting and gelatinization temperatures at different stages were increased by
      heat stress and gradually decreased with grain development under both high
      temperature and control conditions. Gelatinization enthalpy increased initially
      but decreased after peaking at 22 DAP under both control and heat stress
      conditions. High temperature decreased gelatinization enthalpy after 10 DAP.
      Retrogradation percentage value increased with high temperature throughout grain
      development. CONCLUSION: High temperature after pollination changes the dynamics
      of grain filling of waxy maize, which may underlie the observed changes in its
      pasting and thermal properties.

PMID- 24122668
TI  - Down-regulation of BAX gene during carcinogenesis and acquisition of resistance
      to 5-FU in colorectal cancer.
AB  - Carcinogenesis and resistance to chemotherapy could be as results of expression
      variations in apoptosis regulating genes. Changes in the expression of apoptosis
      interfering genes may contribute to colorectal carcinogenesis and resistance to 5
      Flourouracil (5-FU) during treatment schedule period. The present study aimed to
      evaluate the expression of pro-apoptotic and anti-apoptotic genes in colorectal
      cancer tumor tissues, normal adjacent tissues, and tumor colorectal cancer cell
      line during acquiring resistance to 5-FU in HT-29 based on Bolus treatment
      protocol. The normal and tumor tissues were obtained from hospital after surgery
      and total RNA was extracted for expression analysis. The HT-29 colorectal cancer
      cell line was cultured and exposed with 5-FU in three stages based on Bolus
      protocol. The MTT assay and Real Time PCR were carried out to determine the
      sensitivity to the drug and expression of desired genes, respectively. The
      obtained data showed that Proapoptotic genes, BAX and BID, were down-regulated in
      resistant derivate cells compared to wild type HT-29 cells. On the other hand
      Antiapoptotic genes, CIAP1 and XIAP, showed upregulation in resistant cells
      compared to wild type ones. Furthermore, BAX and FAS genes showed down-regulation
      in tumor samples in comparison to normal adjacent tissues. In conclusion, the
      results of our study suggest that BAX down-regulation could contribute as an
      important factor during both colorectal carcinogenesis and cell resistance to 5
      FU.

PMID- 24122671
TI  - What is the efficacy of prophylactic antibiotics in basilar skull fractures?

PMID- 24122673
TI  - Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after
      threatened preterm labour.
AB  - BACKGROUND: In some women, an episode of preterm labour settles and does not
      result in immediate preterm birth. Subsequent treatment with tocolytic agents
      such as oxytocin receptor antagonists may then have the potential to prevent the
      recurrence of preterm labour, prolonging gestation, and preventing the adverse
      consequences of prematurity for the infant. OBJECTIVES: To assess the effects of
      maintenance therapy with oxytocin antagonists administered by any route after an
      episode of preterm labour in order to delay or prevent preterm birth. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 July 2013), sought ongoing and unpublished trials by contacting
      experts in the field and searched the reference lists of relevant articles.
      SELECTION CRITERIA: Randomised controlled trials comparing oxytocin antagonists
      with any alternative tocolytic agent, placebo or no treatment, used for
      maintenance therapy after an episode of preterm labour. DATA COLLECTION AND
      ANALYSIS: We used the standard methods of The Cochrane Collaboration and the
      Cochrane Pregnancy and Childbirth Group. Two review authors independently
      undertook evaluation of methodological quality and extracted trial data. MAIN
      RESULTS: This review includes one trial of 513 women. When compared with placebo,
      atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95%
      confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55),
      or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal
      morbidity, or perinatal mortality. AUTHORS' CONCLUSIONS: There is insufficient
      evidence to support the use of oxytocin receptor antagonists to inhibit preterm
      birth after a period of threatened or actual preterm labour. Any future trials
      using oxytocin antagonists or other drugs as maintenance therapy for preventing
      preterm birth should examine a variety of important infant outcome measures,
      including reduction of neonatal morbidity and mortality, and long-term infant
      follow-up. Future research should also focus on the pathophysiological pathways
      that precede preterm labour.

PMID- 24122674
TI  - Thymectomy for non-thymomatous myasthenia gravis.
AB  - BACKGROUND: Treatments currently used for patients with myasthenia gravis (MG)
      include steroids, non-steroid immune suppressive agents, plasma exchange,
      intravenous immunoglobulin and thymectomy. Data from randomized controlled trials
      (RCTs) support the use of some of these therapeutic modalities and the evidence
      for non-surgical therapies are the subject of other Cochrane reviews. Significant
      uncertainty and variation persist in clinical practice regarding the potential
      role of thymectomy in the treatment of people with MG. OBJECTIVES: To assess the
      efficacy and safety of thymectomy in the management of people with non
      thymomatous MG. SEARCH METHODS: On 31 March 2013, we searched the Cochrane
      Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 3),
      MEDLINE (January 1966 to March 2013), EMBASE (January 1980 to March 2013) and
      LILACS (January 1992 to March 2013) for RCTs. Two authors (RS and GC) read all
      retrieved abstracts and reviewed the full texts of potentially relevant articles.
      These two authors checked references of all manuscripts identified in the review
      to identify additional articles that were of relevance and contacted experts in
      the field to identify additional published and unpublished data. Where necessary,
      authors were contacted for further information. SELECTION CRITERIA: Randomized or
      quasi-randomized controlled trials of thymectomy against no treatment or any
      medical treatment, and thymectomy plus medical treatment against medical
      treatment alone, in people with non-thymomatous MG.We did not use measured
      outcomes as criteria for study selection. DATA COLLECTION AND ANALYSIS: We
      planned that two authors would independently extract data onto a specially
      designed data extraction form and assess risk of bias; however, there were no
      included studies in the review. We would have identified any adverse effects of
      thymectomy from the included trials. MAIN RESULTS: We did not identify any RCTs
      testing the efficacy of thymectomy in the treatment of MG. In the absence of data
      from RCTs, we were unable to do any further analysis. AUTHORS' CONCLUSIONS: There
      is no randomized controlled trial literature that allows meaningful conclusions
      about the efficacy of thymectomy on MG. Data from several class III observational
      studies suggest that thymectomy could be beneficial in MG. An RCT is needed to
      elucidate if thymectomy is useful, and to what extent, in MG.

PMID- 24122672
TI  - Label-retaining, quiescent globose basal cells are found in the olfactory
      epithelium.
AB  - The vertebrate olfactory epithelium (OE) is known for its ability to renew itself
      throughout life as well as to reconstitute after injury. Although this remarkable
      capacity demonstrates the persistence of stem cells and multipotent progenitor
      cells, their nature in the OE remains undefined and controversial, as both
      horizontal basal cells (HBCs) and globose basal cells (GBCs) have features in
      common with each other and with stem cells in other tissues. Here, we investigate
      whether some among the population of GBCs satisfy a key feature of stem cells,
      i.e., mitotic quiescence with retention of thymidine analogue label and
      activation by injury. Accordingly, we demonstrate that some GBCs express
      p27(Kip1) , a member of the Kip/Cip family of cyclin-dependent kinase inhibitors.
      In addition, some GBCs retain bromodeoxyuridine or ethynyldeoxyuridine for an
      extended period when the pulse is administered in neonates followed by a 1-month
      chase. Their identity as GBCs was confirmed by electron microscopy. All spared
      GBCs express Ki-67 in the methyl bromide (MeBr)-lesioned OE initially after
      lesion, indicating that the label-retaining (LR) GBCs are activated in response
      to injury. LR-GBCs reappear during the acute recovery period following MeBr
      exposure, as demonstrated with 2- or 4-week chase periods after labeling. Taken
      together, our data demonstrate the existence of LR-GBCs that are seemingly
      activated in response to epithelial injury and then re-established after the
      initial phase of recovery is completed. In this regard, some among the GBCs
      satisfy a common criterion for functioning like stem cells.

PMID- 24122675
TI  - Genetic variation and possible SNP markers for breeding wheat with low-grain
      asparagine, the major precursor for acrylamide formation in heat-processed
      products.
AB  - BACKGROUND: In products made from wheat (Triticum aestivum) flour, acrylamide
      formation is almost exclusively determined by the level of free asparagine in the
      grain. Genetic variability for grain asparagine content was evaluated in order to
      assess the potential for acrylamide mitigation by breeding. RESULTS: Free
      asparagine levels in the grains of 92 varieties varied from 137 to 471 mg kg-1,
      representing an approximate threefold difference between the low- and high
      asparagine genotypes. Heritability was low, with a value of 32%, indicating that
      breeding cultivars with inherently low grain asparagine would be a challenge. A
      genome-wide scan with single-nucleotide polymorphism (SNP) markers identified
      nine SNPs that were significantly (P < 0.001) associated with variation in free
      asparagine. The significant SNPs were localized on chromosome 5A, and explained
      between 14% and 24% of the observed variation. These putative SNPs are candidates
      for further studies to develop molecular markers. CONCLUSION: Significant genetic
      variation exists for reducing acrylamide precursors in wheat flour, indicating
      that breeding and genetics could play an important role in mitigating the
      acrylamide risk in wheat products. The study identified a region on chromosome 5A
      that could provide a basis for further research to develop functional markers.

PMID- 24122676
TI  - Biodistribution of diclofenac following repeated topical applications of two
      diclofenac sodium formulations to minipigs.
AB  - This study evaluated diclofenac concentrations in plasma, selected hind limb
      tissues and synovial fluid after repeated topical applications of two diclofenac
      formulations. Group 1 Gottingen minipigs (n = 18) were administered diclofenac
      sodium 2.0% topical solution twice daily on days 1-6 and once on day 7. Group 2
      minipigs (n = 18) were administered diclofenac sodium 1.5% topical solution four
      times daily on days 1-6 and twice on day 7. Approximately 20 mg of diclofenac was
      applied daily to a 10 * 15 cm dosing site centered over the patella of the right
      knee. Plasma and tissue samples were collected throughout and analysed for
      diclofenac concentrations using liquid chromatography with tandem mass
      spectrometry. On day 1, diclofenac sodium 2.0% topical solution produced higher
      plasma concentrations compared with the 1.5% formulation; however, after 24 h and
      throughout the remainder of the dosing period, plasma concentrations appeared
      similar, except at the 72 h time point. Twenty-four hours after the final
      application, skin treated with diclofenac sodium 2.0% topical solution retained a
      significantly (p < 0.02) greater amount of diclofenac than the 1.5% formulation.
      Generally, both formulations produced similar diclofenac concentrations in
      synovial fluid, underlying muscle, tendon and bone 24 h after the last
      application. The 2.0% diclofenac formulation applied twice daily delivered
      similar amounts of diclofenac as the 1.5% formulation administered four times
      daily. The skin retained a significant portion of the applied dose to serve as a
      depot for continuous diffusion of diclofenac into underlying tissues and systemic
      circulation.

PMID- 24122677
TI  - Development of a predictive model for daughter pregnancy  rate and
      standardization of voluntary waiting period  in Murrah buffalo.
AB  - A predictive model for daughter pregnancy rate (DPR) in Indian Murrah buffaloes
      has been developed. The data pertaining to first lactation reproduction traits,
      viz., age at first calving (AFC), first service period (FSP), and number of
      services per first conception (NS/FCON) of 719 Murrah buffaloes calved from 1985
      to 2010 at the National Dairy Research Institute (NDRI), Karnal (Haryana), India
      were adjusted against significant environmental influence. First lactation
      reproduction records of 474 Murrah buffaloes were used for determining voluntary
      waiting period (VWP) and estimating DPR. Seven simple and multiple regression
      models in each case were developed where the buffaloes had their first
      insemination after 63 days (DPR 63), 84 days (DPR 84), and 105 days (DPR 105) of
      first calving. Among the seven models (I to VII) for DPR 63, DPR 84, and DPR 105,
      model II, having only FSP as an independent reproduction variable, was found to
      be the best prediction model, based on the four statistical criterions (high
      coefficient of determination (R 2), low mean sum of squares due to error (MSSe),
      conceptual predictive (CP) value, and Bayesian information criterion (BIC)).
      Three linear equations were developed using model II, viz., DPR 63 = 0.0033 (274 
      FSP), DPR 84 = 0.0027 (332 - FSP), and DPR 105 = 0.0027 (310 - FSP). The average
      errors for the prediction of DPR 63, DPR 84, and DPR 105 were 1, 13, and 8 %,
      respectively. Therefore, 63 days of VWP is the optimum period for getting the
      best DPR in Indian Murrah buffaloes.

PMID- 24122679
TI  - The evolution of surgical procedures in the management of duodenal and gastric
      ulcers.
AB  - Surgical procedures for the surgical management of duodenal ulcer had evolved
      through many stages, over the years. It started with gastroenterostomy alone,
      then followed by subtotal gastrectomy, vagotomy alone, vagotomy and gastro
      jejunostomy, vagotomy and pyloroplasty, and highly selective vagotomy - all which
      started as open surgical procedures. Now unless there are complications the
      treatment is essentially medical following the work of Marshall and Warren.
      Currently, even when surgery is indicated, minimal invasive procedures are
      preferred. Four main types of pyloroplasties are well known. They are Weinberg,
      Heinecke-Mikulicz, Finney and Jaboulay. Vagotomy can be truncal, selective, and
      highly selective. Accepted surgical treatment for gastric ulcer is the distal
      gastric resection to include the ulcerated area, but not resecting more than 50
      60% of the stomach. In the uncommon cases of Zollinger-Ellison syndrome,
      aggressive gastric surgery, the use of drugs, and the resection of the tumour
      have all been recommended in appropriate cases. With the discovery of
      Helicobacter pylori and its effective medical treatment, surgery has little role
      in the initial management of peptic ulcer disease. The place of the history of
      the surgical procedures employed earlier in the treatment of this disease would
      remain relevant. 

PMID- 24122680
TI  - Caregivers knowledge and utilization of child health services in an Urban
      District of Lagos, Nigeria.
AB  - BACKGROUND AND OBJECTIVES: Child health, growth and development can be affected
      by the level of knowledge of caregivers and utilization of available child health
      care services. The study objectives was to assess the knowledge and pattern of
      utilization of child health care services among caregivers of children under 5
      years attending Primary Health Care (PHC) centres and factors influencing their
      utilization in Ejigbo Local Council Development Area (LCDA) of Lagos State,
      Nigeria. METHODS: A descriptive cross sectional design was used. An interviewer
      administered questionnaire was used to obtain information from 148 caregivers of
      children under 5 years attending the three PHC facilities in the LCDA. Caregivers
      were selected by systematic random sampling method. Data entry and analysis was
      done using Epi InfoTM statistical software. RESULTS: The mean age of caregivers
      was 30 years (+/- 7.10 SD), about 53 percent are married, 74 percent had at least
      secondary school education, 43 percent are traders and 75 percent had access to
      media facilities. About 70 percent of mothers demonstrated good knowledge of
      preventive health services, less than half (46.3%) reported correctly the use of
      curative services and 88 percent were satisfied with the quality of care
      received. There is an association between caregivers education, occupation and
      their knowledge of use of curative services (p-value <0.05 in both). CONCLUSION:
      This study concludes that the knowledge and use of preventive services among
      respondents is above average, while fewer respondents used curative services
      which were influenced by education and occupation of respondent in Ejigbo, LCDA.

PMID- 24122681
TI  - Cholera outbreak in a southwest community of Nigeria: investigation of risk
      factors and evaluation of a district surveillance system.
AB  - BACKGROUND: Following confirmation of cholera outbreak in a southwest community
      of Nigeria, we set to identify possible risk factors for contracting the disease
      and to evaluate the completeness as well as the representativeness of the cases
      reported to a district health authority. METHODS: Cholera cases were identified
      through an active case search that involved the review of records in health
      facilities and a house-to-house search using the standard case definition in the
      Nigeria integrated disease surveillance and response technical guidelines. Two
      neighborhood controls appropriately matched on age and sex for each case, were
      also identified. An interviewer-administered questionnaire was used to collect
      information on the demographic characteristics and potential risk factors.
      Completeness of reporting of cases notified to the district health authority was
      evaluated using a two source capture-recapture method. In addition, the
      representativeness of the reported cases was determined by comparing the age and
      sex distributions of notified cases to those identified through the active case
      search. RESULTS: Thirty-nine cases were identified, of which 22 consented to
      participate. Contact with a diarrhoea case at home or in the neighborhood within
      the last 7 days prior to illness onset in cases was significantly associated with
      having cholera (Matched triplets Odds Ratio 8.5, 95% CI: 1.36-52.9). The
      completeness of the district surveillance report was estimated to be 54%. In the
      district notification data compared with the active case search data, males <5
      years (31% vs 18%) and females 15 years (3% vs 21%) were significantly over- and
      under-represented, respectively. CONCLUSION: The odds of having cholera were
      increased in those who had contact with a case of diarrhea. Reporting of cases to
      the district health authority was not complete and the surveillance data on
      gender and age grouping were not representative of the cases that occurred in the
      population. There is a need for efficient reporting of cases to the health
      authority during outbreaks in order to improve decision-making and public health
      interventions.

PMID- 24122682
TI  - Diagnostic utility of QuantiFERON-TB gold in-tube in active pulmonary
      Tuberculosis in Nigeria.
AB  - BACKGROUND: The high positive responses obtained in active TB indicate that IGRAs
      may be useful in diagnosing active TB. This study aimed at evaluating the
      usefulness of Quantifer on-TB Gold-in Tube test (QFT-IT) in the diagnosis of
      active TB among Nigerians. METHODS: This study prospectively enrolled sputum
      smear positive TB cases and healthy disease free controls. Basic demographic and
      clinical data were collected using a structured questionnaire. Venous blood was
      collected into the QTF-IT tubes, incubated for 16-24 hours, serum harvested and
      stored at -200C till analysed in a batch. Tuberculin skin test (TST) was also
      done using 5TU and read within 48-72 hours. The performances of QFT-IT and TST
      among the cases and controls were compared. RESULTS: Sixty one TB cases and 41
      controls were enrolled. The mean (SD) age of the TB cases was higher than the
      controls, 35.14+4.3 yrs v 27.8 + 2.1, p<0.001. Forty three (70.5%), 13 (21.3%)
      and 5 (8.2%) of the cases had a positive, negative and indeterminate QFT-IT
      results respectively compared with 14 (34.1%), 25 (61%), and 2 (4.9%) of the
      controls respectively, p values <0.001, 0.005 and 0.05 respectively. Fifty
      eight(95%) and 29(70.7%) of the TB cases and controls had a positive TST result
      respectively while 3 (5%) and 12( 29.3%) of the TB cases and controls had a
      negative TST result respectively, p values 0.003 each .QFT-IT had a sensitivity
      of 76% (95% CI 61.8 -85.2%) while the sensitivity of TST was 96.6% (95% CI 88.5 
      98.3%), p = 0.07. The specificity of QFT-IT was 63.7% (95% CI 46-76%) and 30%
      (95% CI 20- 56%) for TST, p =0.001. Positive Likelihood ratio was 1.7 (95% CI
      1.06-2.85) for QFT-IT and 1.4 (95%CI 1.06-1.8) for TST, p =0.002. Among the
      cases, both TST and QFT-IT were positive in 43(70.5%) and both negative in 1
      (1.6%), and overall test .agreement was 77.7% (Kappa =0.13; p= 0.07). Female sex
      and higher total lymphocytes count were significantly associated with a positive
      QFT results. CONCLUSION: IGRA has a higher specificity and positive likelihood
      ratio in TB cases. Our findings indicate that QFT-IT may be a good adjunct tool
      to diagnose TB disease.

PMID- 24122683
TI  - Endodontic working length of permanent maxillary central incisors in Nigerians.
AB  - BACKGROUND: The permanent maxillary central incisors are critical to dento-facial
      aesthetics in humans. Their restoration in the event of periapical infection or
      traumatic injury to the pulp requires an accurate determination of the root canal
      working length; an important outcome predictor in endodontic treatments. AIM: To
      determine the standard working length of permanent maxillary central incisor in a
      Nigerian population. METHODS: This study was carried out between March 2008 and
      June 2010. The study involved Nigerian patients of both gender, receiving
      endodontic treatment of the permanent maxillary central incisor. The study
      participants were selected based on a predetermined exclusion and inclusion
      criteria. The working lengths of the patient's teeth were determined using the
      radiographic method and Electronic apex locator. RESULTS: The average working
      length of the permanent maxillary central incisor of the patient's was 25.0 +/-
      1.7 mm while the values in males and females were 25.4 +/- 1.2mm and 24.4 +/-
      2.2mm respectively. The male patients had longer working length than the females
      (P<0.05). The study also revealed that the most common indication for endodontic
      treatment in permanent maxillary central incisors in the studied population was
      trauma. CONCLUSION: The endodontic working length of permanent maxillary central
      incisors in adult Nigerian population was greater than that reported in
      Caucasians and Asians. This variation should serve as an important reference for
      endodontic procedures in the maxillary central incisors of adult Nigerians and
      perhaps others nationals from the West Africa sub region.

PMID- 24122684
TI  - Percutaneous endoscopic gastrostomy in ile-ife, Nigeria: an initial report.
AB  - BACKGROUND: Protein-energy malnutrition is a common problem in critically ill
      patient and it is a major cause of accelerated morbidity and mortality in this
      group of patients. Recent dramatic advances in both enteral and parenteral
      nutritional support have ensured that most of these critically ill patients are
      adequately nutritionally supported. Unfortunately, most of these advancements in
      nutritional supports are far from the reach of most patients in developing
      countries. In this report, we highlighted the indications, success, challenges of
      the use of percutaneous endoscopic gastrostomy (PEG) in Nigeria patients.
      PATIENTS AND METHODS: All cases of PEG performed at the Endoscopy Unit of Obafemi
      Awolowo University Teaching Hospitals complex, Ile-Ife, Osun State from January
      2011 and June 2012 were recruited into the study. The data obtained included the
      sociodemographic parameters, indication and duration of the procedure,
      complications, and follow up. RESULTS: During the 18 months study period 645
      upper gastrointestinal endoscopic procedures were performed. Majority
      [601(93.2%)] of the cases were for diagnostic purposes. Six (0.9%) cases of PEG
      were performed. Most (5 of 6) of the patients had central nervous system
      impairment while only one had severe chronic facial infection with naso-oral
      fistula. The median age of patients was 60.5 years. The entire procedure
      including endoscopy lasted an average of 25 minutes with a range of 12-35
      minutes. Only one case had peristoma infection which resolved with antibiotics
      and repeated dressing with povidone iodine. There was no episode of aspiration
      pneumonitis or procedure related mortality. The average follow up was 6 months
      with variable weight gain during the follow up period. CONCLUSION: PEG is a
      simple, cost effective and safe method to rehabilitate nutritionally all
      chronically ill patients in less developed countries such as Nigeria. The need to
      increase awareness and acceptability of PEG among physicians managing such
      patients and the society cannot be overemphasized.

PMID- 24122685
TI  - Evolving pattern of anaesthesia for caesarean section experience at the
      University of Benin Teaching Hospital.
AB  - BACKGROUND: The WHO puts caesarean section rate in Nigeria at 1.8%. This is much
      higher in teaching, specialist and referral hospitals. In our centre University
      of Benin Teaching Hospital (UBTH), the average annual rate is 33.4%. General
      anaesthesia is the predominant choice for caesarean section (C/S) in most
      centres. The trend is increasing towards regional anaesthesia. Many studies have
      reported the trend in several centres. This study examined the evolving pattern
      in our centre. OBJECTIVE: To examine the evolving pattern of anaesthetic
      technique for caesarean section, at the University of Benin Teaching Hospital.
      MATERIALS AND METHODS: A ten-year retrospective period (2001-2010), data were
      pooled from the computerized data system of the department of obstetrics and
      gynaecology. Also, anaesthetic chart and staff records from the department of
      anaesthesiology were studied. Information about C/S, anaesthetic method and
      anaesthetist profile were derived from these sources. The data were analysed and
      presented as simple frequency and nominal data. RESULTS: Six thousand, six
      hundred and eleven C/S were done over the 10-year period. Emergency C/S was 82%,
      while 12% were elective cases. Average annual rate of anaesthetic technique used
      was regional anaesthesia 76.5% and general anaesthesia 23.5%. The use of regional
      anaesthesia grew from 30% in 2001, to 89% in 2010. Number of anaesthetists
      increased from 22 in 2001 to 37 in 2010. CONCLUSION: The study shows an
      increasing use of regional anaesthesia for C/S, predominantly subarachnoid
      blockade.

PMID- 24122686
TI  - Lower extremity peripheral artery disease: prevalence and risk factors among
      adult Nigerians with diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is an important risk factor for development of
      atherosclerosis. Lower extremity peripheral artery disease (LEAD) which is mainly
      due to atherosclerosis has been associated with not only increased risk of lower
      limb amputation but also increased risk of morbidity and mortality from major
      cardiovascular events such as stroke and myocardial infarction. Information on
      the prevalence of peripheral vascular disease is scanty in Nigeria. OBJECTIVE:
      The aim of this study was to determine the prevalence of LEAD and risk factors
      associated with its development in adult Nigerians with type 2 diabetes mellitus.
      METHODS: The study was cross-sectional. Patients were consecutively enrolled in
      the study between August 2009 and May 2010 from the Consultant out-patient
      department, University of Benin Teaching Hospital, Benin-City, Nigeria. LEAD was
      assessed in all the patients using Ankle Brachial Index <0.9 in either leg. The
      Edinburgh Claudication Questionnaire was used to determine if patient had
      symptomatic disease or not. RESULTS: Three hundred and eighty eight diabetic
      patients were enrolled in the study out of which 244 (62.9%) were females. The
      study showed that the prevalence of LEAD was 35.6% when diagnosed using Doppler
      ABI <0.9 in either leg. The ratio of symptomatic to asymptomatic disease was 1:
      7.6. Advancing age, duration of diabetes and concomitant hypertension were
      important risk factors significantly associated with the disease. CONCLUSION:
      LEAD is not uncommon among type 2 diabetes patients in Nigeria and the majority
      were asymptomatic. Advancing age, duration of diabetes and concomitant
      hypertension were important risk factors identified.

PMID- 24122687
TI  - Multidrug-resistant human mycobacterium tuberculosis strain resisted inactivation
      by 10% formalin.
AB  - Multidrug-resistant strain of Mycobacterium tuberculosis (MDR-Tb) and Multidrug
      sensitive Mycobacterium tuberculosis (MDS-Tb) isolated from humans were injected
      subcutaneously into the guinea pigs. One set of infected lungs of animals was
      fixed in 10% formalin pH7.2, while the other set was treated with 75% ethanol 2
      hours prior to fixation in 10% formalin. After six months of fixation, MDS-Tb
      strains were completely inactivated by both methods of fixation. MDR-Tb strains
      resisted inactivation by 10% formalin, but were inactivated by the treatment with
      75% ethanol 2 hours prior to 10% formalin fixation. MDR-Tb was still viable after
      six months in tissue preserved in 10% formalin only. Pretreatment of tissue with
      75% ethanol prior to preservation in 10% formalin gave a better safety precaution
      against MDR-Tb in tissue. Of the 50 infected patients studied during the period,
      4 (8%) haboured MDR-Tb, while 46 (92%) carried MDS-Tb. 

PMID- 24122688
TI  - Sero-prevalence of syphilis among patients with mental illness: comparison with
      blood donors.
AB  - BACKGROUND: Mentally ill individuals (MII) are at risk of acquiring syphilis and
      other sexually transmitted infections. This study aimed at determining sero
      prevalence of syphilis among MII and compare them with voluntary blood donors
      (VBD) at University of Ilorin Teaching Hospital (UITH), Nigeria. METHODS: A cross
      sectional study done between June, 2010 and June 2011, and involving 350 each of
      VBDs and MII in and out-patients of UITH. Serological test was done using
      venereal disease research laboratory (VDRL) and the Treponema Pallidum
      Haemagglutination (TPHA) kit. RESULTS: Of the 700 subjects, 324 (92.6%) MII, and
      349 (99.7%) VBDs were <55 years; 71 (21.4%) MII were Civil Servants compared with
      96 (27.4%) VBDs. Significantly more VBDs had higher education than MII (185 or
      52.9%, and 140 or 40% respectively). Christians constituted the majority (176 or
      50.3%) among MII, and Muslims (210 or 60%) among VBDs. Significantly more married
      VBDs (204/206 or 99.0%) live with spouses; more VBDs consumed alcohol (37 or
      10.6%), smoked (19 or 5.4%), and engaged in extramarital sex (105 or 30.0%).
      Significantly more MII had blood transfusion (40 or 11.4); engaged in sex trade
      (12 or 3.4%); and more syphilis prevalence (5.4%). In addition, more syphilitic
      MII smoked (18 or 94.7%); and all syphilitic MII had psychotic disorders.
      CONCLUSION: The prevalence of syphilis in MII is significantly higher than among
      VBDs. Routine screening of MII is advocated to stem this problem.

PMID- 24122689
TI  - Lower urinary tract pathology evaluation in Nigeria: practice and limitations at
      a private urology centre.
AB  - OBJECTIVE: To review the pattern of lower urinary tract (LUT) pathology, showcase
      the evaluation and management of these conditions and identify if any,
      limitations to the evaluation and management of these conditions at a private
      urology centre in Nigeria. METHOD: We reviewed the medical records of all
      patients presenting with LUT pathology between February 2007 and March 2011. Data
      such as age, sex, patterns of presentation, findings from evaluation, and
      surgical pathology were extracted. RESULTS: In all, 412 patients were seen and
      evaluated. There were 398 males (age range = 40-86 years) with a mean age of 65
      +/-12 yrs and 14 females (age range = 27-71 years) with a mean age of 45 +/-19
      yrs. The commonest symptom seen in the female patients was urge urinary
      incontinence in (13, 92.8%) while the remaining female had stress urinary
      incontinence. All fourteen female patients were evaluated with cystoscopy and
      urodynamic studies. Pressure-flow studies revealed overactive bladder syndrome in
      only 4 patients (28.5%) with urge incontinence with no cause of incontinence
      found in the rest. The most common symptoms in the male patients included LUTS
      (352, 85.4%), hematuria, (21, 5%) and urinary incontinence (6, 1.4%). Evaluation
      consisted of uroflometry, post-void residual (PVR) urine measurement and
      International Prostate Symptom Score (IPSS) assessment respectively in 374
      patients (90%), whereas 303 patients (73%) underwent PSA testing. Seventy five
      patients with LUTS who had PVR > 150 mls under went transrectal ultrasonography
      (TRUS) of the prostate, of whom 61(81%) underwent further TRUS-guided prostate
      biopsies. CONCLUSION: Evaluation of LUT conditions using modern medical
      technology is feasible in a developing country such as Nigeria. While there are
      no unique technological limitations, the costs of treatment in a private urology
      centre may present specific challenges to such comprehensive evaluation of
      patients. Additionally, we show in this study that lower urinary tract conditions
      are predominantly prostate-related and as in other parts of the world, screening
      with PSA increases the detection of organ confined prostate cancer.

PMID- 24122690
TI  - The spectrum of eye injuries in Sagamu, Nigeria.
AB  - BACKGROUND: Eye injuries are major causes of visual morbidity and monocular
      blindness worldwide. The common causes of eye injuries needs to be well defined
      in each community so as to plan for prevention of high morbidity and blindness as
      part of blindness prevention programme. OBJECTIVE: It is necessary to compare the
      trend in causes of ocular injuries in Ogun State after a similar study over 15
      years before. The part played by road traffic accidents [RTA] compared to other
      causes is also to be analysed. METHODOLOGY: This prospective study was carried
      out between July 2004 and June 2005. All cases presenting to the Accident and
      Emergency Unit and Eye Clinic of Olabisi Onabanjo University Teaching Hospital,
      Sagamu, and the 2 private eye clinics in Sagamu town, presenting with any form of
      eye injuries during the study period were included. The biodata, cause and type
      of eye injury, time of injury, time of presentation and treatment offered were
      obtained using a questionnaire. The results were analysed with Epi-Info 2002.
      RESULTS: One hundred and twelve patients were studied. Eighty-one [72.3%] of the
      victims were males; most of them, 36[33.0%] were students and 32 [29.4%]
      artisans. The common causes of eye injuries were RTA 35[31.3%], assault
      22[19.6%], vegetative agents 18 [16.1%] and machine tools 11[9.8%]. Most patients
      presented either within 24 hours, 56[50.0%] or within a week, 34[30.4%] of
      injury, and mostly during the day 86[97.6%]. Most injuries were found in the
      anterior segment 95[84.8%] and most commonly, victims 65[58%] required only
      medications as treatment. CONCLUSION: Majority of eye injuries found in Sagamu
      are treatable and can be handled by an experienced non-ophthalmologist
      successfully and most are now accounted for by RTAs and assault which indicate
      some changes in common causes compared to previous studies in Nigeria.

PMID- 24122691
TI  - Suspected progeria in Nigeria: a case report.
AB  - BACKGROUND: Progeria is a rare fatal genetic condition characterized by an
      appearance of accelerated aging in children. It has an incidence of 1 in 8
      million and results from a mutation of the LMNA gene causing nuclear instability.
      Clinical diagnosis is based on recognition of common clinical features and
      definitive diagnosis is by identifying the mutation in the LMNA gene. Affected
      children usually have a median life span of 13 years. There is no known cure but
      research is ongoing. Currently about 80 children have had a definitive diagnosis
      worldwide with the exclusion of Nigeria. There was however a case report of 3
      siblings in the University of Benin Teaching Hospital, Benin City, Nigeria in
      1990. OBJECTIVE: To present a rare case of suspected progeria in Nigeria. CASE
      REPORT: We report the case of baby IV, a 4-year old girl who presented with
      clinical and radiologic features consistent with progeria. CONCLUSION: Clinical
      and radiologic evidence give a high suspicion of progeria in the index patient.
      Efforts are ongoing to ensure a definitive diagnosis is made; which will be the
      first diagnosed case of progeria in Nigeria.

PMID- 24122692
TI  - Pfeiffer syndrome type 3, a rare and unusual craniosynostosis: case reports from
      Korle Bu Teaching Hospital, Accra, Ghana.
AB  - BACKGROUND: Pfeiffer syndrome is rare in the African population and there are few
      if any published reports from West Africa. OBJECTIVE: To report on two cases of
      Pfeiffer syndrome Type 3 and summarize the clinical characteristics. METHODS: All
      suspected but undiagnosed genetic syndromes presenting to the Children's
      Department over a 10-year period were evaluated by the author. This involved
      direct referral to the author by any member of the Paediatric team in Korle Bu
      Hospital. Full documentation as possible including photographs after seeking
      consent was taken. RESULTS: Two cases of Pfeiffer syndrome Type 3 were recorded
      over the ten year period. CONCLUSION: Pfeiffer syndrome Type 3 is very rare and
      likely to be misdiagnosed. More training in dysmorphology is required in order to
      diagnose unusual syndromes.

PMID- 24122693
TI  - Pyridoxine-dependent epilepsy: an often unrecognized but treatable cause of
      intractable seizures: case report from Korle Bu Teaching Hospital, Accra, Ghana.
AB  - OBJECTIVE: To describe a case of pyridoxine-dependent epilepsy and developmental
      status after treatment. METHODS: An infant who presented with intractable
      seizures was given a therapeutic trial of pyridoxine. This was at the babies unit
      of the Korle Bu Teaching Hospital, Accra, Ghana. Full documentation was done
      together with the patient's clinical course over a period of nearly four years.
      RESULTS: The patient demonstrated definite features of pyridoxine-dependent
      epilepsy as evidenced by prompt resolution of seizures when pyridoxine was
      administered and also as a result of inadvertent withdrawals of pyridoxine when
      child was ill from other causes and abolition of seizures when restarted. The
      child showed evidence of moderate psychomotor delay (speech) after nearly four
      years. CONCLUSION: A very rare case of pyridoxine-dependent epilepsy has been
      described in Ghana. This report highlights the need to suspect it in cases of
      recurrent and intractable neonatal seizures. Pyridoxine should be administered as
      a diagnostic test. Early diagnosis and adequate treatment is paramount in
      managing this condition to prevent long term effects of neurologic function.

PMID- 24122694
TI  - Declines in human papillomavirus infection observed in the vaccine era.

PMID- 24122695
TI  - A principal component analysis of the dynamics of subdomains and binding sites in
      human serum albumin.
AB  - The conformational dynamics of human serum albumin (HSA) was investigated by
      principal component analysis (PCA) applied to three molecular dynamics
      trajectories of 200 ns each. The overlap of the essential subspaces spanned by
      the first 10 principal components (PC) of different trajectories was about 0.3
      showing that the PCA based on a trajectory length of 200 ns is not completely
      convergent for this protein. The contributions of the relative motion of
      subdomains and of the subdomains (internal) distortion to the first 10 PCs were
      found to be comparable. Based on the distribution of the first 3 PC, 10 protein
      conformers are identified showing relative root mean square deviations (RMSD)
      between 2.3 and 4.6 A. The main PCs are found to be delocalized over the whole
      protein structure indicating that the motions of different protein subdomains are
      coupled. This coupling is considered as being related to the allosteric effects
      observed upon ligand binding to HSA. On the other hand, the first PC of one of
      the three trajectories describes a conformational transition of the protein
      domain I that is close to that experimentally observed upon myristate binding.
      This is a theoretical support for the older hypothesis stating that changes of
      the protein onformation favorable to binding can precede the ligand complexation.
      A detailed all atoms PCA performed on the primary Sites 1 and 2 confirms the
      multiconformational character of the HSA binding sites as well as the significant
      coupling of their motions.

PMID- 24122697
TI  - The International Bariatric Club--a worldwide web educational network for
      bariatric professionals.

PMID- 24122698
TI  - Percutaneous electrical neurostimulation of dermatome T6 for appetite reduction
      and weight loss in morbidly obese patients.
AB  - BACKGROUND: A continuous feeling of hunger is the major cause of dietary
      treatment failure in obese patients, making dietary leave. The aim of this study
      was to evaluate the effect of percutaneous electrical neurostimulation (PENS) of
      T6 dermatome on appetite, weight loss and dietary compliance. METHODS: A
      prospective, randomized study was performed. The patients were randomized into
      two groups: those undergoing PENS of dermatome T6 associated with the
      implementation of a 1,200-Kcal diet (group 1) and those following only a 1,200
      Kcal diet (group 2). A third group of obese patients (BMI > 30 Kg/m(2)) with
      fecal incontinence undergoing PENS of posterior tibial nerve was evaluated.
      RESULTS: One hundred five patients were included in the study, 45 in groups 1 and
      2, and 15 in group 3. The median pain perception after PENS of dermatome T6 was
      1. There were no complications. Only the patients in group 1 experienced
      significant reductions of weight, BMI, and appetite. All of the patients in group
      1 experienced appetite reduction compared to 20 % of the patients in group 2 and
      30 % of the patients in group 3 (p < 0.001). Weight loss >=5 Kg was achieved in
      76.7 % of the patients in group 1, 6.7 % of the patients in group 2, and 0 % of
      the patients in group 3 (p < 0.001). Dietary compliance after 12 weeks was 93.3 %
      in group 1, 56.7 % in group 2, and 50 % in group 3(p = 0.006). CONCLUSIONS: PENS
      of dermatome T6 was associated with appetite reduction in all of the patients
      and, along with a proper diet, achieved a significantly greater weight reduction
      than diet alone.

PMID- 24122696
TI  - Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal
      impairment.
AB  - Many factors influence choice of antiepileptic drugs (AEDs), including efficacy
      of the drug for the indication (epilepsy, neuropathic pain, affective disorder,
      migraine), tolerability, and toxicity. The first-generation AEDs and some newer
      AEDs are predominately eliminated by hepatic metabolism. Other recent AEDs are
      eliminated by renal excretion of unchanged drug or a combination of hepatic
      metabolism and renal excretion. The effect of renal and hepatic disease on the
      dosing will depend on the fraction of the AED eliminated by hepatic and/or renal
      excretion, the metabolic isozymes involved, as well as the extent of protein
      binding, if therapeutic drug monitoring is used. For drugs that are eliminated by
      renal excretion, methods of estimating creatinine clearance can be used to
      determine dose adjustments. For drugs eliminated by hepatic metabolism, there are
      no specific markers of liver function that can be used to provide guidance in
      dosage adjustments. Based on studies with probe drugs, the hepatic metabolic
      enzymes are differentially affected depending on the cause and severity of
      hepatic disease, which can aid in predicting dose adjustment when clinical data
      are not available. Several AEDs are also associated with laboratory markers of
      mild hepatic dysfunction and, rarely, more severe hepatic injury. In contrast,
      the risk of renal injury from AEDs is generally low. In general, co-morbid
      hepatic or renal diseases influence the decision for the selection of an AED. For
      some patients dosing changes to their existing AEDs may be appropriate. For
      others, a change to another AED may be a better option.

PMID- 24122699
TI  - Application of a quality by design approach to the cell culture process of
      monoclonal antibody production, resulting in the establishment of a design space.
AB  - This case study describes the application of Quality by Design elements to the
      process of culturing Chinese hamster ovary cells in the production of a
      monoclonal antibody. All steps in the cell culture process and all process
      parameters in each step were identified by using a cause-and-effect diagram.
      Prospective risk assessment using failure mode and effects analysis identified
      the following four potential critical process parameters in the production
      culture step: initial viable cell density, culture duration, pH, and temperature.
      These parameters and lot-to-lot variability in raw material were then evaluated
      by process characterization utilizing a design of experiments approach consisting
      of a face-centered central composite design integrated with a full factorial
      design. Process characterization was conducted using a scaled down model that had
      been qualified by comparison with large-scale production data. Multivariate
      regression analysis was used to establish statistical prediction models for
      performance indicators and quality attributes; with these, we constructed contour
      plots and conducted Monte Carlo simulation to clarify the design space. The
      statistical analyses, especially for raw materials, identified set point values,
      which were most robust with respect to the lot-to-lot variability of raw
      materials while keeping the product quality within the acceptance criteria.

PMID- 24122700
TI  - The evolving role of the Journal of Clinical Pharmacology and its contributions
      to the discipline.

PMID- 24122702
TI  - Characterization of the hypothalamus of Xenopus laevis during development. II.
      The basal regions.
AB  - The expression patterns of conserved developmental regulatory transcription
      factors and neuronal markers were analyzed in the basal hypothalamus of Xenopus
      laevis throughout development by means of combined immunohistochemical and in
      situ hybridization techniques. The connectivity of the main subdivisions was
      investigated by in vitro tracing techniques with dextran amines. The basal
      hypothalamic region is topologically rostral to the basal diencephalon and is
      composed of the tuberal (rostral) and mammillary (caudal) subdivisions, according
      to the prosomeric model. It is dorsally bounded by the optic chiasm and the alar
      hypothalamus, and caudally by the diencephalic prosomere p3. The tuberal
      hypothalamus is defined by the expression of Nkx2.1, xShh, and Isl1, and rostral
      and caudal portions can be distinguished by the distinct expression of Otp
      rostrally and Nkx2.2 caudally. In the mammillary region the xShh/Nkx2.1
      combination defined the rostral mammillary area, expressing Nkx2.1, and the
      caudal retromammillary area, expressing xShh. The expression of xLhx1, xDll4, and
      Otp in the mammillary area and Isl1 in the tuberal region highlights the boundary
      between the two basal hypothalamic territories. Both regions are strongly
      connected with subpallial regions, especially those conveying
      olfactory/vomeronasal information, and also possess abundant intrahypothalamic
      connections. They show reciprocal connections with the diencephalon (mainly the
      thalamus), project to the midbrain tectum, and are bidirectionally related to the
      rhombencephalon. These results illustrate that the basal hypothalamus of anurans
      shares many features of specification, regionalization, and hodology with
      amniotes, reinforcing the idea of a basic bauplan in the organization of this
      prosencephalic region in all tetrapods.

PMID- 24122701
TI  - S100A7 overexpression is a predictive marker for high risk of malignant
      transformation in oral dysplasia.
AB  - Early detection of oral lesions (OLs) at high risk of cancer development is of
      utmost importance for intervention. There is an urgent unmet clinical need for
      biomarkers that allow identification of high-risk OLs. Recently, we identified
      and verified a panel of five candidate protein biomarkers namely S100A7,
      prothymosin alpha, 14-3-3zeta, 14-3-3sigma and heterogeneous nuclear
      ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral
      cancers from normal oral tissues. The objective of our study was to evaluate the
      potential of these candidate protein biomarkers for identification of oral
      dysplastic lesions at high risk of cancer development. Using
      immunohistochemistry, we analyzed expressions of these five candidate protein
      biomarkers in 110 patients with biopsy-proven oral dysplasia and known clinical
      outcome and determined their correlations with p16 expression and HPV 16/18
      status. Kaplan-Meier survival analysis showed reduced oral cancer-free survival
      (OCFS) of 68.6 months (p = 0.007) in patients showing cytoplasmic S100A7
      overexpression when compared to patients with weak or no S100A7 immunostaining in
      cytoplasm (mean OCFS = 122.8 months). Multivariate Cox regression analysis
      revealed cytoplasmic S100A7 overexpression as the most significant candidate
      marker associated with cancer development in dysplastic lesions (p = 0.041,
      hazard ratio = 2.36). In conclusion, our study suggested the potential of S100A7
      overexpression in identifying OLs with dysplasia at high risk of cancer
      development. 

PMID- 24122703
TI  - Prenatal sensory experience affects hatching behavior in domestic chicks (Gallus
      gallus) and Japanese quail chicks (Coturnix coturnix japonica).
AB  - Species-typical developmental outcomes result from organismic and environmental
      constraints and experiences shared by members of a species. We examined the
      effects of enhanced prenatal sensory experience on hatching behaviors by exposing
      domestic chicks (n = 95) and Japanese quail (n = 125) to one of four prenatal
      conditions: enhanced visual stimulation, enhanced auditory stimulation, enhanced
      auditory and visual stimulation, or no enhanced sensory experience (control
      condition). In general, across species, control embryos had slower hatching
      behaviors than all other embryos. Embryos in the auditory condition had faster
      hatching behaviors than embryos in the visual and control conditions. Auditory
      visual condition embryos showed similarities to embryos exposed to either
      auditory or visual stimulation. These results suggest that prenatal sensory
      experience can influence hatching behavior of precocial birds, with the type of
      stimulation being a critical variable. These results also provide further
      evidence that species-typical outcomes are the result of species-typical prenatal
      experiences.

PMID- 24122704
TI  - Perspective and prospective of pretreatment of corn straw for butanol production.
AB  - Corn straw, lignocellulosic biomass, is a potential substrate for microbial
      production of bio-butanol. Bio-butanol is a superior second generation biofuel
      among its kinds. Present researches are focused on the selection of butanol
      tolerant clostridium strain(s) to optimize butanol yield in the fermentation
      broth because of toxicity of bio-butanol to the clostridium strain(s) itself.
      However, whatever the type of the strain(s) used, pretreatment process always
      affects not only the total sugar yield before fermentation but also the
      performance and growth of microbes during fermentation due to the formation of
      hydroxyl-methyl furfural, furfural and phenolic compounds. In addition, the
      lignocellulosic biomasses also resist physical and biological attacks. Thus,
      selection of best pretreatment process and its parameters is crucial. In this
      context, worldwide research efforts are increased in past 12 years and
      researchers are tried to identify the best pretreatment method, pretreatment
      conditions for the actual biomass. In this review, effect of particle size,
      status of most common pretreatment method and enzymatic hydrolysis particularly
      for corn straw as a substrate is presented. This paper also highlights crucial
      parameters necessary to consider during most common pretreatment processes such
      as hydrothermal, steam explosion, ammonia explosion, sulfuric acid, and sodium
      hydroxide pretreatment. Moreover, the prospective of pretreatment methods and
      challenges is discussed.

PMID- 24122705
TI  - Bioconversion of glycerine pitch into a novel yellow-pigmented P(3HB-co-4HB)
      copolymer: synergistic effect of ammonium acetate and polymer characteristics.
AB  - Glycerine pitch waste generated from oleochemical industry was exploited as a
      carbon source for poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB))
      copolymer production by a novel, yellow-pigmented bacterium Cupriavidus sp.
      USMAHM13 to improve the economics of microbial polyhydroxyalkanoate production
      and to establish a feasible waste management approach. Medium optimization using
      response surface methodology through shake-flask fermentation had led to the
      accumulation of P(3HB-co-51%4HB) copolymer using a combination of glycerine pitch
      (10 g/l), 1,4-butanediol (8.14 g/l), and ammonium acetate (2.39 g/l). P(3HB-co
      4HB) copolymers with 4HB monomer compositions ranged from 3 to 40 mol% were
      obtained through batch fermentation in a bioreactor using different
      concentrations of ammonium acetate. The copolymers exhibited a wide range of
      material properties depending on the monomer composition and type of carbon
      sources. P(3HB-co-40%4HB) was a typical random copolymer, whereas other P(3HB-co
      4HB) produced were blend copolymers. Carotenoid pigment which was produced
      simultaneously with the polymer production was found to have negligible effect on
      the mechanical and thermal properties of the P(3HB-co-4HB) copolymer films.

PMID- 24122706
TI  - Antioxidant and biochemical activities of mixed ligand complexes.
AB  - Novel 4-aminoantipyrine based mixed ligand metal complexes with the Schiff bases
      ofL1(L1-4(furanylmethyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one and
      L2/ L3/ L4are 2-(2-chlorobenzylideneamino)phenol, 2-(3
      chlorobenzylideneamino)phenol, 2-(4-chlorobenzylideneamino)phenol were
      synthesized. The structures of the mixed ligand complexes were established by
      analytical and spectral techniques. They were screened for in vitro antimicrobial
      activity against bacteria and fungi by disc diffusion method. The interaction of
      metal complexes with CT-DNA was investigated by UV-vis, cyclic voltammetry,
      viscosity and thermal denaturation studies.DNA interaction studies suggest that
      metal complex binds to calf thymus DNA (CT-DNA) through intercalation mode.
      Superoxide dismutase activity of these complexes has also been studied. The free
      ligands and their metal complexes have been tested for in vitro antioxidant
      activity by the reduction of 1,1-diphenyl-2-picryl hydrazyl (DPPH).The
      antioxidant activities of the complexes were studied and compared with the
      activity of ascorbic acid. Cu(II) complex showed superior antioxidant activity
      than other complexes. The solvatochromic behaviour of complexes was also
      performed in various solvents.

PMID- 24122707
TI  - Dynamic changes in the composite microbial system MC1 during and following its
      rapid degradation of lignocellulose.
AB  - To monitor the dynamics of the composite microbial system MC1 during its
      degradation of lignocellulose and to improve our understanding of the microbial
      communities involved in this biomass conversion, MC1 was characterized at eight
      time points over an 18-day, thermophilic, aerobic, static cultivation. We found
      the microbial communities to be dynamic, rhythmic consortia capable of changing
      in response to lignocellulose degradation. The growth curve over 18 days was M
      shaped. Based on the quantitative changes in five major components of MC1
      (Clostridium straminisolvens CSK-1, Clostridium sp. FG4, Pseudoxanthomonas sp. M1
      3, Brevibacillus sp. M1-5, and Bordetella sp. M1-6), reduction in rice straw
      weight, cellulase (CMCase) activity, xylanase activity, and changes in medium pH,
      we found that the process comprised two identifiable phases. Rapid degradation
      occurred from day 0 to day 9, while the post-rapid degradation phase included
      days 10 to 18. Day 3 and day 12 were two key time points in the rapid degradation
      phase and post-rapid degradation phase, respectively. Two anaerobes, C.
      straminisolvens CSK-1 and Clostridium sp. FG4, dominated the MC1 system from day
      0 to day 18.

PMID- 24122708
TI  - Exopolysaccharides and antimicrobial biosurfactants produced by Paenibacillus
      macerans TKU029.
AB  - Paenibacillus macerans TKU029 can produce exopolysaccharides (EPSs; 3.46 g/L) and
      a biosurfactant (1.78 g/L) in a medium with 2 % (w/v) squid pen powder as the
      sole carbon/nitrogen source. The biosurfactant can reduce the surface tension of
      water from 72.30 to 35.34 mN/m at a concentration of 2.76 g/L and reach an
      emulsification index of 56 % after a 24-h reaction with machine oil. This
      biosurfactant is stable at 121  degrees C for 20 min, over a pH range from 3 to
      11, and in <5 % salt solutions. It also shows significant antimicrobial activity,
      which remains active after treatment at 121  degrees C and at pH values from 4 to
      10, against Escherichia coli BCRC13086, Staphylococcus aureus BCRC10780, Fusarium
      oxysporum BCRC32121 and Aspergillus fumigatus BCRC30099. Furthermore, human skin
      shows from 37.3 to 44.3 % hydration after being treated with TKU029 EPSs for 180
      min. These results imply that EPSs and the biosurfactant from this strain have
      potential in cosmetics, for removal of oil contamination, and as antimicrobial
      agents.

PMID- 24122709
TI  - Comparison of alcoholic fermentation performance of the free and immobilized
      yeast on water hyacinth stem pieces in medium with different glucose contents.
AB  - Ethanol fermentation with Saccharomyces cerevisiae cells was performed in medium
      with different glucose concentrations. As the glucose content augmented from 200
      to 250 g/L, the growth of the immobilized cells did not change while that of the
      free cells was reduced. At higher glucose concentration (300, 350, and 400 g/L),
      the cell proliferation significantly decreased and the residual sugar level
      sharply augmented for both the immobilized and free yeast. The specific growth
      rate of the immobilized cells was 27-65 % higher than that of the free cells, and
      the final ethanol concentration in the immobilized yeast cultures was 9.7-18.5 %
      higher than that in the free yeast cultures. However, the immobilized yeast
      demonstrated similar or slightly lower ethanol yield in comparison with the free
      yeast. High fermentation rate of the immobilized yeast was associated with low
      unsaturation degree of fatty acids in cellular membrane. Adsorption of S.
      cerevisiae cells on water hyacinth stem pieces in the nutritional medium
      decreased the unsaturation degree of membrane lipid and the immobilized yeast
      always exhibited lower unsaturation degree of membrane lipid than the free yeast
      in ethanol fermentation.

PMID- 24122710
TI  - Ornithine carbamoyltransferase unfolding states in the presence of urea and
      guanidine hydrochloride.
AB  - Ornithine carbamoyltransferase folding/unfolding is a complex and not completely
      understood process. Our experimental results suggest that ornithine
      carbamoyltransferase interacts in a completely different way with urea and
      guanidine hydrochloride. In fact, we noticed that, increasing concentration from
      0.0 to 8.0 M of the two additives, the enzyme follows a simple one-step
      transition mechanism in the presence of guanidine hydrochloride, with two
      macroscopic states (the native and the denatured one) significantly populated,
      whereas in the presence of urea a lot of different protein states can be detected
      and analyzed. Circular dichroism and UV-visible spectroscopy reveal a similar
      mechanism of perturbation at high temperature, with opening of hydrophobic core
      and a significant loss in alpha-helix structure in the presence of guanidine
      hydrochloride that cannot be found in the presence of urea.

PMID- 24122711
TI  - Effect of the oral intake of probiotic Pediococcus acidilactici BA28 on
      Helicobacter pylori causing peptic ulcer in C57BL/6 mice models.
AB  - Probiotic lactic acid bacteria are being proposed to cure peptic ulcers by
      reducing colonization of Helicobacter pylori within the stomach mucosa and by
      eradicating already established infection. In lieu of that, in vitro inhibitory
      activity of pediocin-producing probiotic Pediococcus acidilactici BA28 was
      evaluated against H. pylori by growth inhibition assays. Further, chronic
      gastritis was first induced in two groups of C57BL/6 mice by orogastric
      inoculation with H. pylori with polyethylene catheter, and probiotic P.
      acidilactici BA28 was orally administered to study the eradication and cure of
      peptic ulcer disease. H. pylori and P. acidilactici BA28 were detected in gastric
      biopsy and fecal samples of mice, respectively. A probiotic treatment with P.
      acidilactici BA28, which is able to eliminate H. pylori infection and could
      reverse peptic ulcer disease, is being suggested as a co-adjustment with
      conventional antibiotic treatment. The study provided an evidence of controlling
      peptic ulcer disease, by diet mod

PMID- 24122712
TI  - Isolation, purification and characterisation of an organic solvent-tolerant Ca2+
      dependent protease from Bacillus megaterium AU02.
AB  - A new organic solvent-tolerant strain Bacillus megaterium AU02 which secretes an
      organic solvent-tolerant protease was isolated from milk industry waste.
      Statistical methods were employed to achieve optimum protease production of 43.6
      U/ml in shake flask cultures. The productivity of the protease was increased to
      53 U/ml when cultivated under controlled conditions in a 7-L fermentor. The
      protease was purified to homogeneity by a three-step process with 24 % yield and
      specific activity of 5,375 U/mg. The molecular mass of the protease was found to
      be 59 kDa. The enzyme was active over a wide range of pH (6.0-9.0), with an
      optimum activity at pH 7.0 and temperature from 40 to 70  degrees C having an
      optimum activity at 50  degrees C. The thermal stability of the enzyme increased
      significantly in the presence of CaCl2, and it retained 90 % activity at 50 
      degrees C for 3 h. The Km and Vmax values were determined as 0.722 mg/ml and
      0.018 U/mg respectively. The metalloprotease exhibited significant stability in
      the presence of organic solvents with log P values more than 2.5, nonionic
      detergents and oxidising agent. An attempt was made to test the synthesis of
      aspartame precursor (Cbz-Asp-Phe-NH2) which was catalysed by AU02 protease in the
      presence of 50 % DMSO. These properties of AU02 protease make it an ideal choice
      for enzymatic peptide synthesis in organic media.

PMID- 24122713
TI  - Nitrogen removal by Chelatococcus daeguensis TAD1 and its denitrification gene
      identification.
AB  - Chelatococcus daeguensis TAD1 was demonstrated to be an aerobic denitrifier. It
      can utilize not only nitrate and nitrite but also ammonium at high temperature
      (about 50  degrees C). The strain had the capability to remove 122.7 and 71.7 mg
      L-1 NH4+-N by 18 h at 50 and 30  degrees C, respectively. Triplicate
      heterotrophic nitrification experiments showed that 32.3 % of removed NH4+-N was
      completely converted to nitrogen gas by 18 h at 50  degrees C. The
      denitrification genes involved in C. daeguensis TAD1 were identified and
      sequenced. It was found that the genes responsible for denitrification in TAD1
      were napA, nirK, cnorB, and nosZ. Taken together, TAD1 can be an effective
      candidate for simultaneous nitrification and denitrification at high temperature.

PMID- 24122714
TI  - Unstable genomes elevate transcriptome dynamics.
AB  - The challenge of identifying common expression signatures in cancer is well
      known, however the reason behind this is largely unclear. Traditionally variation
      in expression signatures has been attributed to technological problems, however
      recent evidence suggests that chromosome instability (CIN) and resultant
      karyotypic heterogeneity may be a large contributing factor. Using a well-defined
      model of immortalization, we systematically compared the pattern of genome
      alteration and expression dynamics during somatic evolution. Co-measurement of
      global gene expression and karyotypic alteration throughout the immortalization
      process reveals that karyotype changes influence gene expression as major
      structural and numerical karyotypic alterations result in large gene expression
      deviation. Replicate samples from stages with stable genomes are more similar to
      each other than are replicate samples with karyotypic heterogeneity. Karyotypic
      and gene expression change during immortalization is dynamic as each stage of
      progression has a unique expression pattern. This was further verified by
      comparing global expression in two replicates grown in one flask with known
      karyotypes. Replicates with higher karyotypic instability were found to be less
      similar than replicates with stable karyotypes. This data illustrates the
      karyotype, transcriptome, and transcriptome determined pathways are in constant
      flux during somatic cellular evolution (particularly during the macroevolutionary
      phase) and this flux is an inextricable feature of CIN and essential for cancer
      formation. The findings presented here underscore the importance of understanding
      the evolutionary process of cancer in order to design improved treatment
      modalities.

PMID- 24122715
TI  - Hyaluronic acid gel weight: a nonsurgical option for the management of paralytic
      lagophthalmos.
AB  - OBJECTIVES/HYPOTHESIS: Management of lagophthalmos should be a priority in the
      treatment of patients with facial palsy. The aim of the study was to evaluate the
      safety and efficacy of injecting hyaluronic acid gel into the upper eyelid as a
      nonsurgical alternative for patients with temporary facial palsy. METHOD/STUDY
      DESIGN: Retrospective study of 26 patients treated with hyaluronic acid gel
      injected into the pretarsal region of the upper eyelid. Measurements taken before
      and after treatment were standardized and compared using digitized photographs.
      Patients were followed up for 1 year, and overall outcomes were assessed.
      RESULTS: All patients initially demonstrated improvement in lagophthalmos, which
      decreased to 0.0 mm. After 1 month, a significant increase in lagophthalmos was
      observed in two patients (initial fissure of 8 and 9 mm), and a platinum weight
      was implanted to control keratopathy. The remaining patients (initial
      lagophthalmos below 6.5 mm) maintained the improvement until facial restoration.
      Only three patients had recurrent lagophthalmos (2 mm) due to resorption, which
      was resolved by injecting an additional 0.3 cc. The mean improvement in
      lagophthalmos was 4.6 mm (range, 3.5-6.5 mm). Complications included transient
      ecchymosis and minimal blepharoptosis due to nonreabsorption in five patients.
      These patients were successfully treated with hyaluronidase. CONCLUSIONS:
      Hyaluronic acid gel has proven effective in reducing paralytic lagophthalmos and
      controlling keratopathy in patients with temporary facial palsy, especially those
      with palpebral fissure with attempted closure no greater than 6.5 mm. Injection
      of hyaluronic acid gel is safe, quick, and easily performed. In addition, it is
      more cost-effective than surgery.

PMID- 24122716
TI  - Codeine-related adverse drug reactions in children following tonsillectomy: a
      prospective study.
AB  - OBJECTIVES/HYPOTHESIS: To prospectively determine factors associated with
      codeine's adverse drug reactions (ADRs) at home in a large homogenous population
      of children undergoing outpatient tonsillectomy. STUDY DESIGN: Prospective,
      genotype blinded, observational study with a single group and repeated ADR
      measures documented by parents at home. METHODS: A total of 249 children 6 to 15
      years of age scheduled for tonsillectomy were enrolled. The primary outcome was
      number of daily codeine-related ADRs. We examined the number and type of ADR by
      race and by days and further modeled factors potentially associated with ADR risk
      in a subcohort of white children. Sedation following a dose of codeine was a
      secondary outcome measure. Parents recorded their children's daily ADRs and
      sedation scores during postoperative days (POD) 0 to 3 at home. RESULTS: Diaries
      were returned for 134 children, who were given codeine. A total of 106 (79%)
      reported at least one ADR. The most common ADRs were nausea,
      lightheadedness/dizziness for white children and nausea, and vomiting for African
      American children. In a subcohort of white children <= 45 kg, increased ADR risk
      was associated with the presence of one or more full function CYP2D6 alleles (P <
      0.001), POD (P < 0.001), and sex (P = 0.027). Increased pain intensity (P =
      0.009) and PODs 0 and 1 (P = 0.001) contributed to a higher sedation risk.
      Neither obstructive apnea nor predicted CYP2D6 phenotype were associated with
      sedation risk. CONCLUSIONS: Our results provide evidence that multiple factors
      are associated with codeine-related ADRs and support the FDA recommendation to
      avoid codeine's routine use following tonsillectomy in children.

PMID- 24122717
TI  - Genetic affinities of Ukrainians from the maternal perspective.
AB  - The area of what is now the Ukraine has been the arena of large-scale demographic
      processes that may have left their traces in the contemporary gene pool of
      Ukrainians. In this study, we present new mitochondrial DNA data for 607
      Ukrainians (hypervariable segment I sequences and coding region polymorphisms).
      To study the maternal affinities of Ukrainians at the level of separate
      mitochondrial haplotypes, we apply an original technique, the haplotype co
      occurrence analysis. About 20% of the Ukrainian maternal gene pool is represented
      by lineages highly specific to Ukrainians, but is scarcely found in other
      populations. About 9% of Ukrainian mtDNA lineages are typical for peoples of the
      Volga region. We also identified minor gene pool strata (1.6-3.3%), each of which
      is common in Lithuanians, Estonians, Saami, Nenets, Cornish, and the populations
      of the North Caucasus.

PMID- 24122718
TI  - Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein
      apheresis.
AB  - RATIONALE: Lipoprotein apheresis (LA) reduces low-density lipoprotein (LDL)
      levels in patients with severe familial hypercholesterolemia (FH). We have
      recently reported that >30% of plasma proprotein convertase subtilisin/kexin 9
      (PCSK9) is bound to LDL, thus we predicted that LA would also reduce plasma PCSK9
      levels by removing LDL. OBJECTIVE: Pre- and post-apheresis plasma from 6 patients
      with familial hypercholesterolemia on 3 consecutive treatment cycles was used to
      determine changes in PCSK9 levels. METHODS AND RESULTS: LA drastically reduced
      plasma LDL (by 77 +/- 4%). Concomitantly, PCSK9 levels fell by 52 +/- 5%,
      strongly correlating with the LDL drop (P=0.0322; r(2)=0.26), but not with
      decreases in triglyceride (49 +/- 13%) or high-density lipoprotein levels (18 +/-
      2%). Levels of albumin, creatinine, and CK-MB did not show significant changes
      after LA. Similar to LDL, PCSK9 levels returned to pretreatment values between
      cycles (2-week intervals). Fractionation of pre- and post-apheresis plasma showed
      that 81 +/- 11% of LDL-bound PCSK9 and 48 +/- 14% of apolipoprotein B-free PCSK9
      were removed. Separation of whole plasma, purified LDL, or the apolipoprotein B
      free fraction through a scaled-down, experimental dextran sulfate cellulose beads
      column produced similar results. CONCLUSIONS: Our results show, for the first
      time, that modulation of LDL levels by LA directly affects plasma PCSK9 levels,
      and suggest that PCSK9 reduction is an additional benefit of LA. Because the loss
      of PCSK9 could contribute to the LDL-lowering effect of LA, then (1) anti-PCSK9
      therapies may reduce frequency of LA in patients currently approved for therapy,
      and (2) LA and anti-PCSK9 therapies may be used synergistically to reduce
      treatment burden.

PMID- 24122719
TI  - Bone morphogenetic protein 2 signaling negatively modulates lymphatic development
      in vertebrate embryos.
AB  - RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly
      regulated during development. Although several factors that promote the
      differentiation of LECs in embryonic development have been identified, those that
      negatively regulate this process are largely unknown. OBJECTIVE: Our aim was to
      delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic
      development. METHODS AND RESULTS: BMP2 signaling negatively regulates the
      formation of LECs. Developing LECs lack any detectable BMP signaling activity in
      both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos
      and mouse embryonic stem cell-derived embryoid bodies substantially decrease the
      emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31
      and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated
      expression of prospero homeobox protein 1 during development. CONCLUSIONS: Our
      data identify BMP2 as a key negative regulator for the emergence of the lymphatic
      lineage during vertebrate development.

PMID- 24122721
TI  - Differences between easy- and difficult-to-mill chickpea (Cicer arietinum L.)
      genotypes. Part II: protein, lipid and mineral composition.
AB  - BACKGROUND: Part I introduced the concept of easy- and difficult-to-mill chickpea
      genotypes, the broad chemical composition of their seed fractions and proposed
      mechanistic explanations for physical differences consistent with observed
      variation in milling ease. Part II continues this research by delving deeper into
      the amino acid, fatty acid and mineral components. RESULTS: No association
      between fatty acid composition and ease of milling was observed. However,
      particular amino acids and mineral elements were identified that further support
      roles of lectins, pectins and mineral-facilitated binding in the adhesion of
      chickpea seed coat and cotyledons. CONCLUSION: These differences suggest
      underlying mechanisms that could be exploited by breeding programmes to improve
      milling performance. This study shows that the content and composition of amino
      acids, fatty acids and minerals within different chickpea tissues vary with seed
      type (desi and kabuli) and within desi genotypes in ways that are consistent with
      physical explanations of how seed structure and properties relate to milling
      behaviour.

PMID- 24122722
TI  - Percutaneous endovascular Y-stenting of a malignant superior vena cava and
      innominate vein obstruction.
AB  - Superior vena cava syndrome (SVCS) is considered one of the telltale signs of a
      terminal malignant process. We describe a successful endovascular desobliteration
      of a subtotal occluded SVC and the left innominate vein using a Y-stent technique
      in a 46-year-old female with a mediastinal nodal metastasis of a relapsing renal
      cell carcinoma. Complete clinical improvement in the symptoms within the first 24
      hours of the procedure and no complication were observed. This report describes
      endovascular stenting of the SVC as a palliation therapy to overcome the severe
      clinical symptoms of SVCS besides surgical or chemotherapy in mediastinal
      malignancy masses. 

PMID- 24122720
TI  - MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of
      pulmonary vascular fibroblasts.
AB  - RATIONALE: Pulmonary hypertensive remodeling is characterized by excessive
      proliferation, migration, and proinflammatory activation of adventitial
      fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The
      mechanisms responsible for generation/maintenance of this phenotype remain
      unknown. OBJECTIVE: We hypothesized that aberrant expression of microRNA-124 (miR
      124) regulates this activated fibroblast phenotype and sought to determine the
      signaling pathways through which miR-124 exerts effects. METHODS AND RESULTS: We
      detected significant decreases in miR-124 expression in fibroblasts isolated from
      calves and humans with severe pulmonary hypertension. Overexpression of miR-124
      by mimic transfection significantly attenuated proliferation, migration, and
      monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas
      anti-miR-124 treatment of control fibroblasts resulted in their increased
      proliferation, migration, and monocyte chemotactic protein-1 expression.
      Furthermore, the alternative splicing factor, polypyrimidine tract-binding
      protein 1, was shown to be a direct target of miR-124 and to be upregulated both
      in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The
      effects of miR-124 on fibroblast proliferation were mediated via direct binding
      to the 3' untranslated region of polypyrimidine tract-binding protein 1 and
      subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and
      p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic
      protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial
      hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is
      suppressed by histone deacetylases and that treatment of hypertensive fibroblasts
      with histone deacetylase inhibitors increased miR-124 expression and decreased
      proliferation and monocyte chemotactic protein-1 production. CONCLUSIONS: Stable
      decreases in miR-124 expression contribute to an epigenetically reprogrammed,
      highly proliferative, migratory, and inflammatory phenotype of hypertensive
      pulmonary adventitial fibroblasts. Thus, therapies directed at restoring miR-124
      function, including histone deacetylase inhibitors, should be investigated.

PMID- 24122723
TI  - The value of decreased plasma gelsolin levels in patients with systemic lupus
      erythematosus and rheumatoid arthritis in diagnosis and disease activity
      evaluation.
AB  - Plasma gelsolin, the extracellular gelsolin isoform, circulates in the blood of
      healthy individuals at a concentration of 200 +/- 50 mg/l and plays important
      roles in the extracellular actin-scavenging system during tissue damage.
      Decreased plasma gelsolin levels have been observed in many inflammatory
      diseases. In the present study, the variation and potential clinical application
      of plasma gelsolin levels in patients with systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA) were analysed. Plasma samples and clinical data were
      collected from informed and consenting participants: 47 SLE patients, 60 RA
      patients and 50 age- and gender-matched healthy individuals. Semiquantitative
      western blotting was used for measuring plasma gelsolin levels. The plasma
      gelsolin levels in patients with SLE and RA were significantly decreased compared
      with healthy controls (145.3 +/- 40.4 versus 182.7 +/- 38.3 mg/l and 100.8 +/- 36
      versus 182.7 +/- 38.3 mg/l, p < 0.001), and plasma gelsolin levels were
      especially lower in RA than in SLE patients (100.8 +/- 36 versus 145.3 +/- 40.4
      mg/L, p < 0.001). An analysis of the clinical data showed a significant negative
      correlation between plasma gelsolin levels and SLE Disease Activity Index
      (SLEDAI) scores (r = 0.659, p < 0.001) but no correlation between plasma gelsolin
      levels and RA disease activity score 28 (DAS28) (r = 0.076, p = 0.569). Different
      clinical characteristics were also observed in SLE and RA patients with normal
      and decreased plasma gelsolin levels.This study found significantly lower plasma
      gelsolin levels in patients with SLE and RA compared with healthy controls and
      documented a significant negative correlation between plasma gelsolin levels and
      SLEDAI, which suggested the potential clinical application of plasma gelsolin in
      SLE diagnosis and disease activity evaluation. The different clinical
      characteristics in SLE and RA patients with normal and decreased plasma gelsolin
      levels indicate differences in the basis of the diseases.

PMID- 24122724
TI  - High morbidity and mortality found for high-risk, non-muscle-invasive bladder
      cancer.

PMID- 24122725
TI  - Sonodynamic antitumor effect of a novel sonosensitizer on S180 solid tumor.
AB  - PURPOSE: The purpose of this study was to evaluate the sonodynamically induced
      antitumor effect of a novel sonosensitizer (DVDMS) in mice bearing sarcoma 180
      solid tumors. METHODS: In order to determine the optimum timing of ultrasound
      exposure after administration of DVDMS, a three-dimensional optical imaging
      system (IVIS spectrum) was used to observe the biodistribution of DVDMS in S180
      tumor. The antitumor effects were estimated by the tumor inhibition ratio (volume
      and weight) after sonodynamic therapy. RESULTS: The experiments suggested that
      DVDMS has a preferential localization in tumors, but a low accumulation in most
      normal tissues. A significant synergistic effect of ultrasound combined with
      DVDMS was obtained when the load power indicated 4 W and DVDMS dose was above 2
      mg/kg. At day 14 after DVDMS-SDT, the tumor volume inhibition ratio was 56.27%.
      In addition, the tumor weight inhibition ratio after the synergistic treatment
      was 55.37%, which was obviously stronger than ultrasound treatment alone (23.85%)
      and DVDMS alone (23.15%). Moreover, no metastasis occurred to the tumors in the
      SDT-treated mice compared with the control group. CONCLUSIONS: DVDMS is a
      potential sensitizer for sonodynamic cancer therapy. The antitumor effect of
      ultrasound could be enhanced in the presence of DVDMS, which might be involved in
      a sonochemical mechanism.

PMID- 24122726
TI  - Isothermal amplification of DNA using quadruplex primers with fluorescent
      pteridine base analogue 3-methyl isoxanthopterin.
AB  - We previously developed a method, known as quadruplex priming amplification
      (QPA), which greatly simplifies DNA amplification and quantification assays. QPA
      employs specific primers based on GGGTGGGTGGGTGGG (G3T) sequence, which upon
      polymerase elongation spontaneously dissociates from the target and folds into a
      stable quadruplex. Fluorescent nucleotide analogs, when incorporated into these
      primers, emit light upon quadruplex formation and permit simple, specific, and
      sensitive quantification without the attachment of probe molecules. Here, we
      studied optical [fluorescence and circular dichroism (CD)] and thermodynamic
      properties of the G3T sequence and variants incorporating 3-methylisoxanthopterin
      (3MI), a highly fluorescent nucleotide analog suitable for QPA. CD studies
      demonstrate that the incorporation of 3MI does not change the overall tertiary
      structure of G3T; however, thermal unfolding experiments revealed that it
      significantly destabilizes the quadruplex. Enzymatic studies revealed that Taq
      and Bst are practically unable to incorporate any nucleotides opposite to
      template 3MI. Based on this knowledge, we designed QPA assays with truncated
      targets that demonstrate efficient amplification around 55 degrees C. Overall,
      these studies suggest that 3MI-based QPA is a useful assay for DNA amplification
      and detection.

PMID- 24122727
TI  - Utilizing dynamic light scattering as a process analytical technology for protein
      folding and aggregation monitoring in vaccine manufacturing.
AB  - Protein aggregation is a common challenge in the manufacturing of biological
      products. It is possible to minimize the extent of aggregation through timely
      measurement and in-depth characterization of aggregation. In this study, we
      demonstrated the use of dynamic light scattering (DLS) to monitor inclusion body
      (IB) solubilization, protein refolding, and aggregation near the production line
      of a recombinant protein-based vaccine candidate. Our results were in good
      agreement with those measured by size-exclusion chromatography. DLS was also used
      to characterize the mechanism of aggregation. As DLS is a quick, nonperturbing
      technology, it can potentially be used as an at-line process analytical
      technology to ensure complete IB solubilization and aggregate-free refolding.

PMID- 24122728
TI  - Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and
      adult rats.
AB  - Adolescent rats are more sensitive to the rewarding and less sensitive to the
      aversive properties of various drugs of abuse than their adult counterparts.
      Given a nationwide increase in use of "bath salts," the present experiment
      employed the conditioned taste aversion procedure to assess the aversive effects
      of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common
      constituent in "bath salts," in adult and adolescent rats. As similar drugs
      induce thermoregulatory changes in rats, temperature was recorded following MDPV
      administration to assess if thermoregulatory changes were related to taste
      aversion conditioning. Both age groups acquired taste aversions, although these
      aversions were weaker and developed at a slower rate in the adolescent subjects.
      Adolescents increased and adults decreased body temperature following MDPV
      administration with no correlation to aversions. The relative insensitivity of
      adolescents to the aversive effects of MDPV suggests that MDPV may confer an
      increased risk in this population.

PMID- 24122729
TI  - Effects of botulinum toxin A on patient-specific keloid fibroblasts in vitro.
AB  - OBJECTIVES/HYPOTHESIS: To test whether therapeutic effects of botulinum toxin A
      on patient- specific keloid tissue can be reproduced on the cellular level.
      Specifically, effects on cell proliferation and expression of growth factors and
      cytokines relevant for wound healing were to be tested. STUDY DESIGN:
      Experimental study including patient specific cell cultures of keloids. METHODS:
      Patient-specific keloid tissue was tested in a cell culture model for effects of
      botulinum toxin incubation on cell proliferation and expression of the following
      cytokines and growth factors: IL-6 (interleukin-6), VEGF (vascular endothelial
      growth factor), TGF-beta (transforming growth factor-beta). RESULTS: None of the
      tested parameters of human keloid tissue were affected by botulinum toxin A
      incubation. CONCLUSION: The present study does not add evidence to suggest a
      significant therapeutic role of botulinum toxin injections for the treatment of
      keloids. LEVEL OF EVIDENCE: N/A.

PMID- 24122730
TI  - Impact of technology on cytology outcome in cervical cancer screening of young
      and older women.
AB  - Little is known about age-dependent variation in outcomes of cervical cytology
      with modern technologies. This population-based study evaluated age-dependent
      changes after routine implementation of ThinPrep and SurePath technology in two
      independent laboratories, and controlled for time trends in a third laboratory
      using manually read conventional cytology continually. Data were collected from
      the Danish National Health Care Registers. For each laboratory, we compared
      proportions of abnormal cytology defined as atypical squamous cells of
      undetermined significance or worse (ASCUS+) by age and technology phase. The
      study included 489,960 cytological samples with no recent abnormality from women
      aged 23-59 years, routinely screened between 1998 and 2007. Implementation of
      SurePath liquid-based cytology (LBC) was followed by an increase in abnormal
      cytology in women aged 23-29 years from 4.6 to 6.1%, relative proportion (RP):
      1.31 [95% confidence interval (CI): 1.08-1.61], and a decrease in women aged 45
      59 years from 2.9 to 2.0%, RP: 0.71 (95% CI: 0.60-0.83). Implementation of
      ThinPrep LBC was followed by a decrease in abnormal cytology both in women aged
      23-29 years from 7.7 to 6.8%, RP: 0.89 (95% CI: 0.78-1.02) and in women aged 45
      59 years from 3.4 to 1.0%, RP: 0.30 (95% CI: 0.24-0.37). With implementation of
      imaging-assisted reading, regardless of the brand of technology, the proportion
      of abnormality increased by around 30% in all age groups (range from 19 to 41%).
      In the laboratory with unchanged technology no trends in abnormality proportions
      were observed. The impact of LBC implementation on cytological abnormality
      proportions varied considerably across age groups. 

PMID- 24122731
TI  - Preprodynorphin-expressing neurons constitute a large subgroup of somatostatin
      expressing GABAergic interneurons in the mouse neocortex.
AB  - Dynorphins, leumorphin, and neoendorphins are preprodynorphin (PPD)-derived
      peptides and ligands for kappa-opioid receptors. Using an antibody to PPD C
      terminal, we investigated the chemical and molecular characteristics of PPD
      expressing neurons in mouse neocortex. PPD-immunopositive neuronal somata were
      distributed most frequently in layer 5 and less frequently in layers 2-4 and 6
      throughout neocortical regions. Combined labeling of immunofluorescence and
      fluorescent mRNA signals revealed that almost all PPD-immunopositive neurons
      expressed glutamic acid decarboxylase but not vesicular glutamate transporter,
      indicating their gamma-aminobutyric acid (GABA)ergic characteristics, and that
      PPD-immunopositive neurons accounted for 15% of GABAergic interneurons in the
      primary somatosensory area. As GABAergic interneurons were divided into several
      groups by specific markers, we further examined the chemical characteristics of
      PPD-expressing neurons by the double immunofluorescence labeling method. More
      than 95% of PPD-immunopositive neurons were also somatostatin (SOM)
      immunopositive in the primary somatosensory, primary motor, orbitofrontal, and
      primary visual areas, but only 24% were SOM-immunopositive in the medial
      prefrontal cortex. In the primary somatosensory area, PPD-immunopositive neurons
      constituted 50%, 79%, 55%, and 17% of SOM-immunopositive neurons in layers 2-3,
      4, 5, and 6, respectively. Although SOM-expressing neurons contained calretinin-,
      neuropeptide Y-, nitric oxide synthase-, and reelin-expressing neurons as
      subgroups, only reelin immunoreactivity was detected in many PPD-immunopositive
      neurons. These results indicate that PPD-expressing neurons constitute a large
      subgroup of SOM-expressing cortical interneurons, and the PPD/SOM-expressing
      GABAergic neurons might serve not only as inhibitory elements in the local
      cortical circuit, but also as modulators for cortical neurons expressing kappa
      opioid and/or SOM receptors.

PMID- 24122732
TI  - Activity rating scales in adult muscle disease: what do they actually measure?
AB  - INTRODUCTION: There is a diversity of rating scales that assess function in
      muscle disease. Definitive knowledge of the content covered by these scales would
      help in making choices. METHODS: We searched for activity rating scales used for
      muscle disease and assessed their content by linking scale items to the
      International Classification of Functioning, Disability and Health (ICF) and the
      muscle regions they cover. RESULTS: Of the 119 scales found, 19 muscle disease
      specific and 9 generic scales were prioritized for analysis. These 28 scales
      contained 457 items, from which 1145 concepts were identified and 160 were
      unique. Of these concepts, 97.8% could be linked to the ICF, most to the
      activities and participation domain (68.7%), followed by environmental factors
      (22.5%) and body functions (6.6%). Global muscle function was assessed most
      frequently, followed by lower and upper extremity function. CONCLUSIONS: This
      content comparison should allow for a better-informed choice of activity rating
      scales for muscle disease.

PMID- 24122733
TI  - Differences between easy- and difficult-to-mill chickpea (Cicer arietinum L.)
      genotypes. Part I: broad chemical composition.
AB  - BACKGROUND: Ease of milling is an important quality trait for chickpeas (Cicer
      arietinum L.) and involves two separate processes: removal of the seed coat and
      splitting of cotyledons. Four chickpea genotypes (two desi types, one kabuli type
      and one interspecific hybrid with 'wild' C. echinospermum parentage) of differing
      ease of milling were examined to identify associated seed composition differences
      in the seed coat, cotyledons and their junctions (abaxial and adaxial). RESULTS:
      Several components in different fractions were associated with ease of milling
      chickpea seeds: primarily soluble and insoluble non-starch polysaccharides
      (including pectins) and protein at the seed coat and cotyledon junctions, and the
      lignin content of the seed coat. CONCLUSION: This study shows that the chemical
      composition of chickpea does vary with seed type (desi and kabuli) and within
      desi genotypes in ways that are consistent with physical explanations of how seed
      structure and properties relate to milling behaviour.

PMID- 24122734
TI  - Current and emerging options for the drug treatment of narcolepsy.
AB  - Narcolepsy/hypocretin deficiency (now called type 1 narcolepsy) is a lifelong
      neurologic disorder with well-established diagnostic criteria and etiology.
      Narcolepsy is a chronic sleep disorder characterized by excessive daytime
      sleepiness (EDS) and symptoms of dissociated rapid eye movement sleep such as
      cataplexy (sudden loss of muscle tone), hypnagogic hallucinations (sensory events
      that occur at the transition from wakefulness to sleep), sleep paralysis
      (inability to perform movements upon wakening or sleep onset), and nocturnal
      sleep disruption. As these symptoms are often disabling, most patients need life
      long treatment. The treatment of narcolepsy is well defined, and, traditionally,
      amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used
      for clinical management to improve EDS and sleep attacks, whereas tricyclic
      antidepressants have been used as anticataplectics. However, treatments have
      evolved to better-tolerated compounds such as modafinil or armodafinil (for EDS)
      and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics).
      In addition, night-time administration of a short-acting sedative, c
      hydroxybutyrate (sodium oxybate), has been used for the treatment for EDS and
      cataplexy. These therapies are almost always needed in combination with non
      pharmacologic treatments (i.e., behavioral modification). A series of new drugs
      is currently being tested in animal models and in humans. These include a wide
      variety of hypocretin agonists, melanin- concentrating hormone receptor
      antagonists, antigenspecific immunopharmacology, and histamine H3 receptor
      antagonists/inverse agonists (e.g., pitolisant), which have been proposed for
      specific therapeutic applications, including the treatment of Alzheimer's
      disease, attention-deficit hyperactivity disorder, epilepsy, and more recently,
      narcolepsy. Even though current treatment is strictly symptomatic, based on the
      present state of knowledge of the pathophysiology of narcolepsy, we expect that
      more pathophysiology-based treatments will be available in the near future.

PMID- 24122736
TI  - Impact of small-for-gestational age (SGA) status on gentamicin pharmacokinetics
      in neonates.
AB  - We compared gentamicin pharmacokinetics among neonates born small-for-gestational
      age (SGA) and appropriate for gestational age (AGA). We further compared
      gentamicin pharmacokinetics in subgroups of AGA and SGA neonates born preterm and
      term and treated within and after the initial week of age. Steady state peak and
      trough serum gentamicin concentrations were used to calculate clearance (Cl),
      elimination constant (Kel), volume of distribution (Vd), and half-life (t1/2 ) in
      infants (n = 236) who received >=48 hours therapy. Statistical analyses (SPSS
      17.0) included chi-square and the non-parametric Mann-Whitney U-test. SGA infants
      treated early (<=7days) (n = 29) and at postmenstrual ages <=32 weeks (n = 23)
      had significantly lower median Kel (0.069/h vs. 0.081/h and 0.067/h vs. 0.075/h)
      and clearance (0.58 mL/kg/min vs. 0.68 mL/kg/min and 0.46 mL/kg/min vs. 0.65
      mL/kg/min), compared to those born AGA. There were no significant differences in
      pharmacokinetic profiles with later therapy or at more mature ages. The prolonged
      half-life of gentamicin may need to be considered in dosing regimens for preterm
      SGA infants in the initial week of life. 

PMID- 24122735
TI  - Li-Fraumeni and Li-Fraumeni-like syndrome among children diagnosed with pediatric
      cancer in Southern Brazil.
AB  - BACKGROUND: Pediatric cancers are a feature in patients with Li-Fraumeni syndrome
      and its variant Li-Fraumeni-like syndrome (LFS/LFL). To the best of the authors'
      knowledge, TP53 germline mutations are currently the only molecular defect known
      to be associated with this disease. Recently, a specific germline mutation in
      this gene, p.R337H, has been reported at a high prevalence in Brazil. METHODS:
      The prevalence of LFS/LFL was investigated in children with cancer who were
      diagnosed with tumors on the LFS/LFL spectrum and in a small consecutive series
      of controls without cancer. The prevalence of the germline p.R337H mutation and
      of other germline TP53 mutations was investigated in a general group of children
      with cancer and exclusively in children fulfilling the clinical criteria for
      LFS/LFL, respectively. RESULTS: Among the 65 children without cancer, 1.5% had a
      family history of LFL whereas of the 292 children with cancer, 25.3% had a family
      history of LFL (P < .001). Screening for the p.R337H mutation identified 11
      carriers (3.7%), 9 of whom were diagnosed with adrenocortical carcinomas (ACC)
      and 2 of whom were diagnosed with choroid plexus carcinomas. One of the ACC
      probands was homozygous mutant. The Brazilian founder haplotype and loss of
      heterozygosity at the p.R337H locus were present in all carriers. In addition,
      direct sequencing of the entire TP53 coding region and gene rearrangement
      analysis of probands fulfilling the criteria for LFL (Eeles 2 criteria, Birch
      and/or Chompret criteria) and who were negative for the p.R337H mutation revealed
      a DNA-binding domain pathogenic mutation, p.G245S, in 1 child. CONCLUSIONS: TP53
      p.R337H testing should be offered to Brazilian children diagnosed with ACC and
      choroid plexus carcinoma. A significant percentage of children with cancer in
      southern Brazil fulfill the criteria for LFL and should be referred for genetic
      risk assessment.

PMID- 24122738
TI  - Dopamine-induced hypophagia is mediated by D1 and 5HT-2c receptors in chicken.
AB  - The present study was designed to examine the effects of intracerebroventricular
      (ICV) injection of Dopamine (10, 20 and 40 nmol), L-DOPA (dopamine precursor;
      62.5, 125 and 250 nmol), 6-OHDA (dopamine inhibitor; 75, 150 and 300 nmol), SCH
      23390 (D1 antagonist; 2.5, 5 and 10 nmol), AMI-193 (D2 antagonist; 2.5, 5 and 10
      nmol), NGB2904 (D3 antagonist; 3.2, 6.4 and 12.8 nmol), L-741 T742 (D4
      antagonist; 1.5, 3 and 6 nmol) on food intake in FD3 chickens. At following,
      birds were ICV injected using 8-OH-DPAT (5-HT1A agonist; 15.25 nmol) and SB242084
      (5-HT2C antagonist; 1.5 MUg) prior dopamine (40 nmol) injection. Cumulative food
      intake was determined until 3 h post-injection. According to the results,
      dopamine significantly decreased food intake in chickens (p<0.05). The inhibitory
      effect of dopamine on food intake was decreased by SCH 23390 pretreatment
      (P<0.05), but AMI-193, NGB2904 and L-741, 742 had no effect on food intake
      induced by dopamine. In addition, hypophagic effect of dopamine was attenuated by
      SB242084 (P<0.05), but 8-OH-DPAT had no effect. These results suggest that
      dopamine decrease food intake via D1 receptor and there is an interaction between
      dopaminergic and serotonergic systems via 5-HT2C receptor in chickens.

PMID- 24122739
TI  - The State-Trait Hopelessness Scale: development and testing.
AB  - Hopelessness is predictive in the development of coronary heart disease (CHD) and
      can persist in patients after a CHD event, adversely affecting recovery.
      Hopelessness may represent a temporary response (state) or a chronic outlook
      (trait). Common hopelessness measures fail to differentiate state from trait
      hopelessness, a potentially important differentiation for treatment. The State
      Trait Hopelessness Scale (STHS) was developed and pilot tested with two groups of
      college students (n = 39 and 190) and patients with CHD (n = 44). The instrument
      was then used with 520 patients, confirming reliability (Cronbach's alpha) for
      the State (.88) and Trait (.91) subscales and concurrent and predictive validity.
      Separate exploratory factor analyses showed two factors (hopelessness present or
      hopelessness absent) for the State and Trait subscales, accounting for 58.9% and
      57.3% of variance, respectively. These findings support future use of the tool in
      clinical settings and in intervention studies focused on hopelessness. 

PMID- 24122737
TI  - Complications of primary and revision functional endoscopic sinus surgery for
      chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The goal of this study was to determine the incidence of
      major complications following primary and revision functional endoscopic sinus
      surgery (FESS). In addition, this study aimed to determine factors associated
      with the occurrence of complications including patient and provider
      characteristics and the use of image guidance system (IGS) technology. STUDY
      DESIGN: Retrospective cohort analysis of California and Florida all-payer
      databases from 2005 to 2008. METHODS: The rates of major surgical complications
      (skull base, orbital, and hemorrhagic) after primary and revision FESS were
      calculated, and bivariate analyses were performed to investigate relationships of
      complications with demographic and clinical characteristics. A multivariate model
      was used to determine risk factors for the occurrence of major complications.
      RESULTS: Among 78,944 primary FESS cases, 288 major complications were identified
      representing a complication rate of 0.36% (95% CI 0.32%-0.40%). The major
      complication rate following revision cases (n = 19; 0.46%) and primary cases (n =
      288; 0.36%) was similar (OR = 1.26; 95% CI 0.79-2.00). Multivariate analysis
      showed that patients who were >40 years old, had a primary payer of Medicaid, had
      surgery involving the frontal sinus, or had image guidance during surgery were at
      higher risk for major complications. CONCLUSION: The rate of major complications
      (0.36%) associated with primary FESS is lower than earlier reports. The rate of
      major complications following revision FESS (0.46%) was found to be similar to
      primary cases. IGS, insurance status, age, and extent of surgery were found to be
      associated with an increased risk of major complications following FESS. LEVEL OF
      EVIDENCE: 2C.

PMID- 24122740
TI  - Technical note: a histological technique for detecting the cryptic preservation
      of erythrocytes and soft tissue in ancient human skeletonized remains.
AB  - Bone samples from a Middle Bronze Age (ca., 1600-1300 BC) site were prepared for
      histological analysis. Preliminary results suggested that components of bone
      marrow remained preserved. To verify these findings and optimize the sample
      preparation procedure, we conducted experiments varying the type of acid used to
      decalcify the bones for histology preparation, as well as the exposure time to
      the demineralizing agents and thickness of sections taken from the samples for
      slide preparation. Subsequent examination of the slides revealed the presence of
      well-preserved erythrocytes and other cellular structures consistent with bone
      marrow. Our results demonstrate that the traditional methods used to prepare bone
      samples for histology may be adjusted to improve the quality of the soft tissue
      architecture and cellular morphology for histological observation.

PMID- 24122741
TI  - Which approach is better: bilateral versus unilateral thalamic deep brain
      stimulation in patients with fragile X-associated tremor ataxia syndrome.
AB  - Fragile X-associated tremor ataxia syndrome (FXTAS) is a relatively recently
      described condition that is frequently misdiagnosed as essential tremor and then
      occasionally treated as such with deep brain stimulation (DBS) to the nucleus
      ventralis intermedius of the thalamus (Vim). Reports of ataxia worsening after
      bilateral Vim DBS in FXTAS patients are conflicting, and only five FXTAS patients
      treated with Vim DBS for intractable tremor have been reported in the literature,
      three of whom having undergone a bilateral procedure. We report a patient who
      underwent a staged Vim DBS procedure, with excellent contralateral hand tremor
      control and no worsening of ataxia after the first procedure, but immediate
      worsening of his ataxia after the second one, arguing in favor of a unilateral
      surgical approach for intractable tremor in FXTAS. 

PMID- 24122742
TI  - Excess of extracolonic non-endometrial multiple primary cancers in MSH2 germline
      mutation carriers over MLH1.
AB  - BACKGROUND: The lynch syndrome (LS) tumor spectrum involves colorectal cancer
      (CRC), endometrial cancer (EC), and less frequently various extracolonic non
      endometrial cancers (non-EC). The organ-specific survival rates of these patients
      are well defined, however, the collective survival of all-cancers combined (CRC +
      EC + non-EC) are unclear. METHODS: Fifty-two MSH2 patients and 68 MLH1 patients
      were followed for a median of 6.3 years after diagnosis of first cancer,
      regardless of type. The proportions of CRC only, EC, non-EC, and multiple primary
      cancers were compared between the two genotypes. Kaplan-Meier curves were
      developed for survival comparisons. RESULTS: MSH2 patients present less
      frequently with only CRC (37% MSH2, 62% MLH1, P = 0.0096), manifest more multiple
      primary cancers (38% MSH2, 18% MLH1, P = 0.013), develop more extracolonic
      cancers (62% MSH2, 38% MLH1, P = 0.003), non-EC only cancers (46% MSH2, 24% MLH1,
      P = 0.028) and carry a greater risk for urinary tract cancer (UTC) (13.4% MSH2,
      1.5% MLH1, P = 0.024). There was no difference in 10-year survival between the
      two groups (P = 0.4). CONCLUSION: The additional propensity for UTC in MSH2
      carriers argues in favor of UTC screening in MSH2 individuals. Other types of
      cancer screening should be tailored to the expression history of the specific LS
      mutation.

PMID- 24122743
TI  - Pharmacokinetics, bioavailability and tissue distribution of geniposide following
      intravenous and peroral administration to rats.
AB  - In order to characterize the pharmacokinetics, bioavailability and tissue
      distribution of geniposide following intravenous and peroral administration to
      rats, a reliable gradient HPLC-based method has been developed and validated.
      After p.o. administration of geniposide, the peak concentration of geniposide in
      plasma occurred at 1 h and plasma geniposide was eliminated nearly completely
      within 12 h. The AUC(0->infinity) values of geniposide were 6.99 +/- 1.27 h .
      ug/ml and 6.76 +/- 1.23 h . ug/ml after i.v. administration of 10 mg/kg and p.o.
      administration of 100 mg/kg of geniposide, respectively. The absolute oral
      bioavailability (%F) of geniposide was calculated as 9.67%. After p.o.
      administration of geniposide, the AUC(0->4h) values in tissues were in the order
      of kidney > spleen > liver > heart > lung > brain. This study improved the
      understanding of the pharmacokinetics, bioavailability and tissue distribution of
      geniposide in rats and may provide a meaningful basis for clinical application of
      such a bioactive compound of herbal medicines.

PMID- 24122744
TI  - Acceptability and reliability of multiple mini interviews for admission to
      otolaryngology residency.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the acceptability and reliability of the
      Multiple Mini Interview (MMI) for the selection of applicants to an
      Otolaryngology-Head and Neck (OTL-HNS) residency program. STUDY DESIGN:
      Prospective observational study. METHODS: Canadian medical graduates applying to
      the OTL-HNS residency program at McGill University in 2011 and 2012 underwent a 7
      station MMI. Upon completion, the major stakeholders commented on and rated
      various aspects of the MMI using a 7-point Likert scale. Descriptive statistics
      were used to analyze the quantitative portion of the exit survey, while content
      analysis and thematic description was applied to qualitative data. Interrater
      reliability was examined with intraclass correlation coefficients. RESULTS: Data
      was collected from 45 applicants and 18 evaluators. The majority of applicants
      (>80%) felt that the MMI helped them present their strengths and was free of any
      gender, cultural, or age bias. Assessors (>85%) agreed the MMI evaluated a valid
      range of competencies, and that it tested more aspects of an applicant than did
      traditional interviews. Both applicants and assessors (>70%) agreed that the MMI
      was a fair process, and both preferred it over the traditional interview.
      Overall, interrater reliability of the MMI was good. CONCLUSION: This is the
      first study to examine how the MMI interview process can be adapted for admission
      to an OTL-HNS residency program, while showing both good acceptability for all
      major stakeholders and good reliability.

PMID- 24122745
TI  - Improving referring physicians' understanding of electromyography reports when
      qualifying radiculopathies: a need for standardized terminology.
AB  - Electromyographic (EMG) reporting of radiculopathies is not standardized, and the
      terminology used in reports can be misinterpreted by referring physicians.
      Physicians who refer patients for EMG studies at the Mayo Clinic were surveyed
      about their understanding of 6 different EMG interpretations of an S1
      radiculopathy. Of 45 responders, the terms "acute, active," "chronic, inactive,"
      and "old" were interpreted consistently by 95%, 98%, and 84% of responders,
      respectively. Physicians had the most difficulty understanding the meaning of
      "chronic" in isolation, "chronic, active," or "old with uncompensated
      denervation." These findings suggest a need to educate referring physicians on
      the meaning of the terms used in EMG reports and to develop standard guidelines
      for qualifying radiculopathies. Based on our observations, guidelines for the
      reporting of radiculopathies have been adopted in the Mayo Clinic Florida EMG
      laboratory.

PMID- 24122746
TI  - Limited proteolysis of natively unfolded protein 4E-BP1 in the presence of
      trifluoroethanol.
AB  - Natively unfolded (intrinsically disordered (ID) proteins) have been attracting
      an increasing attention due to their involvement in many regulatory processes.
      Natively unfolded proteins can fold upon binding to their metabolic partners.
      Coupled folding and binding events usually involve only relatively short motifs
      (binding motifs). These binding motifs which are able to fold should have an
      increased propensity to form a secondary structure. The aim of the present work
      was to probe the conformation of the intrinsically disordered protein 4E-BP1 in
      the native and partly folded states by limited proteolysis and to reveal regions
      with a high propensity to form an ordered structure. Trifuoroethanol (TFE) in low
      concentrations (up to 15 vol%) was applied to increase the helical population of
      protein regions with a high intrinsic propensity to fold. When forming helical
      structures, these regions lose mobility and become more protected from proteases
      than random/unfolded protein regions. Limited proteolysis followed by mass
      spectrometry analysis allows identification of the regions with decreased
      mobility in TFE solutions. Trypsin and V8 proteases were used to perform limited
      proteolysis of the 4E-BP1 protein in buffer and in solutions with low TFE
      concentrations at 37 degrees C and at elevated temperatures (42 and 50 degrees
      C). Comparison of the results obtained with the previously established 4E-BP1
      structure and the binding motif illustrates the ability of limited proteolysis in
      the presence of a folding assistant (TFE) to map the regions with high and low
      propensities to form a secondary structure revealing potential binding motifs
      inside the intrinsically disordered protein.

PMID- 24122747
TI  - The effect of a speaking valve on laryngeal aspiration and penetration in
      children with tracheotomies.
AB  - OBJECTIVES/HYPOTHESIS: Alterations in swallowing can occur after tracheotomy and
      can result in varying degrees of aspiration. In tracheotomized adult patients,
      use of a Passy Muir Speaking Valve (PMV) has been shown to decrease laryngeal
      penetration and aspiration of foods and liquids. The objective of this study was
      to determine if the PMV has a similar effect on laryngeal penetration and
      aspiration in tracheotomized children. STUDY DESIGN: This is a prospective case
      control study. METHODS: Pediatric patients with tracheotomies who were able to
      tolerate the PMV were identified. Modified barium swallow (MBS) was performed
      with and without the PMV. Two consistencies, thin liquids and purees, were used.
      Two speech language pathologists (SLPs), who were blinded to the PMV status,
      reviewed the recorded MBSs. Three swallows of each consistency were graded on an
      8 point Penetration-Aspiration Scale. Residue in the vallecula, piriform sinuses,
      and posterior pharyngeal wall was graded. RESULTS: Twelve patients were included
      for analysis. Laryngeal penetration and aspiration was decreased with purees over
      liquids (P = 0.5 and P = 0.005, respectively) with either the sham valve or the
      PMV. The presence of the PMV decreased piriform sinus residue (P = 0.01);
      however, it did not demonstrate a decrease in laryngeal aspiration or
      penetration. CONCLUSION: Unlike in adults, the presence of PMV did not decrease
      laryngeal aspiration or penetration in children with tracheotomies. It did,
      however, improve piriform sinus residue. LEVEL OF EVIDENCE: 3b.

PMID- 24122748
TI  - Combined extracapsular and intracapsular tonsillectomy: lower pole capsule
      preservation.

PMID- 24122749
TI  - Microbiological quality of raw and processed wild and cultured edible snails.
AB  - BACKGROUND: An increasing interest in snail farming in Greece and other European
      countries has been observed. Despite the fact that edible snails have been
      involved with problems of Salmonella spp. contamination, there are to our
      knowledge only limited studies regarding microbiological safety and hygiene of
      such products. Enumeration of microbial populations and presence/absence of
      Salmonella spp. in snail meat and intestines of wild Cornu aspersum, Helix
      lucorum and cultured Cornu aspersum snails from indoor/outdoor type farms was
      conducted. Furthermore, snail-processing steps were simulated in the laboratory
      and the population reduction in snail meat was determined. RESULTS: Microbial
      populations were higher in intestines than snail meat in almost all cases.
      Escherichia coli/coliforms and Enterococcus spp. populations were lower in the
      intestines and snail meat of cultured C. aspersum. Salmonella spp. were detected
      in the intestines and snail meat of wild snails only. The high levels of
      bacterial populations were considerably reduced after the appropriate processing.
      CONCLUSION: The lower populations of E. coli/coliforms, Enterococcus spp. and
      especially the absence of Salmonella spp. in cultured snails show that the
      controlled conditions decrease the possibility of pathogen presence and
      contribute to food safety and public health.

PMID- 24122750
TI  - Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a
      systematic review and meta-analysis.
AB  - The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio
      (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta
      analysis to determine the predictable value of NLR in the clinical outcome of CRC
      patients. The analysis was carried out based on the data from 16 studies (19
      cohorts) to evaluate the association between NLR and overall survival (OS) and
      progression-free survival (PFS) in patients with CRC. In addition, the
      relationship between NLR and clinicopathological parameters was assessed. Hazard
      ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as
      the effect size estimate. Our analysis results indicated that elevated
      pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS
      (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also
      significantly associated with the poorer differentiation of the tumor (OR: 1.574,
      95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493,
      95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic
      value for patients with CRC. NLR should be monitored in CRC patients for rational
      stratification of the patients and adjusting the treatment strategy. 

PMID- 24122754
TI  - Old dogs and new tricks: defective peripheral regulatory T cell generation in
      aged mice.
AB  - Tolerance is a developmentally acquired property of the vertebrate immune system,
      in part ensured by regulatory CD4+ lymphocytes (Treg cells) expressing the Foxp3
      transcription factor. Recent work has shown that thymic emigrants are the
      preferential source of peripherally generated Treg cells. A new report in this
      issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 2598
      2604] describes a cell autonomous defect in Foxp3 induction in aged CD4+ cells in
      mice. Immune homeostasis becomes progressively less robust as ontogeny gives way
      to aging, and a key feature of senescence is thymic involution and the impaired T
      cell turnover that follows. In this Commentary, we discuss the implications of
      these recent findings for our understanding of the induction of tolerance to
      peripheral antigens in aging.

PMID- 24122753
TI  - TLRs control hematopoiesis during infection.
AB  - Recent research has shown that (i) Toll-like receptor (TLR) agonists drive
      hematopoietic stem and progenitor cells (HSPCs) to proliferate and differentiate
      along the myeloid lineage in vitro, and (ii) direct TLR-mediated stimulation of
      HSPCs also promotes macrophage differentiation in vivo following infection. These
      new insights demonstrate that TLR signaling in HSPCs, in addition to other TLR
      dependent mechanisms, can contribute to HSPC expansion and myeloid
      differentiation after infection. Evidence is, therefore, mounting that direct TLR
      induced programming of hematopoiesis plays a key role in host defense by rapidly
      replenishing the innate immune system with the cells needed to deal with
      pathogens. 

PMID- 24122755
TI  - Unsuspected allies: chemotherapy teams up with immunity to fight cancer.
AB  - Chemotherapy has been a standard treatment for cancer for the past several
      decades and has long been suspected to cause systemic immune suppression.
      However, in recent years it has become clear that the immune status of a patient
      is an independent prognostic factor for chemotherapeutic efficacy, and that T
      cell-mediated responses actively contribute to the tumor destruction triggered by
      some chemotherapeutic agents. In this respect, the induction of immunogenic cell
      death by these compounds appears to be crucial. In this issue of the European
      Journal of Immunology, a study by Hannesdottir et al. [Eur. J. Immunol. 2013. 43:
      2718-2729] demonstrates a crucial role for the IFN signaling molecule STAT1
      during doxorubicin and Lapatinib treatment of HER2/Neu-driven mammary carcinomas.
      The genotoxic anthracycline doxorubicin causes immunogenic cancer cell death and
      is expected to depend on the immune system, but the dual ErbB2/HER2/Neu and
      ErbB1/EGFR inhibitor Lapatinib also turns out to cause immune reactivity.
      Although CD8+ T cells are partially involved in this phenomenon, doxorubicin, and
      Lapatinib also affect the myeloid infiltrate (i.e. tumor-associated macrophages
      and monocytes) in tumors. In this Commentary, we place these findings in the
      context of current knowledge and propose new avenues for future research.

PMID- 24122760
TI  - Prediction of overall survival or progression free survival by disease control
      rate at week 8 is independent of ethnicity: Western versus Chinese patients with
      first-line non-small cell lung cancer treated with chemotherapy with or without
      bevacizumab.
AB  - Categorizations of best response observed at week 8 (between week 3 and 14) of
      first-line treatment in two studies of bevacizumab plus chemotherapy in Western
      (878 patients) and Chinese (198 patients) patients with non-small cell lung
      cancer were assessed together with baseline prognostic factors in multivariate
      parametric models to predict overall survival (OS) and progression free survival
      (PFS). Predictive performances of the models were assessed by simulating multiple
      replicates of the studies. Disease control rate (DCR) was the best response
      categorization to predict OS and PFS. In the OS model, DCR fully captured
      bevacizumab effect. For PFS, DCR did not fully capture bevacizumab treatment
      effect. The models adequately predicted OS and PFS distributions in each arm as
      well as bevacizumab hazard ratio (HR) for OS and PFS, for example, in Western
      patients (model prediction [95% prediction interval]: 0.84 [0.71-0.98] vs.
      observed: 0.77 for OS and 0.59 [0.49-0.72] vs. observed: 0.58 for PFS).
      Covariates in the models captured endpoint differences seen in Chinese patients.
      There was no impact of Chinese ethnicity on the DCR relationship to OS or PFS.
      DCR predicted OS benefit with bevacizumab in first-line NSCLC patients. Western
      data can be used to inform design of studies in Chinese patients. 

PMID- 24122762
TI  - Nursing organizational climates in public and private hospitals.
AB  - BACKGROUND: Researchers study climate to gain an understanding of the
      psychological environment of organizations, especially in healthcare
      institutions. Climate is considered to be the set of recurring patterns of
      individual and group behaviour in an organization. There is evidence confirming a
      relationship between ethical climate within organizations and job satisfaction.
      OBJECTIVES: The aim of this study is to describe organizational climate for
      nursing personnel in public and private hospitals and to confirm the
      relationships among the climate variables of such hospitals. MATERIALS AND
      METHODS: A correlational study was carried out to measure the organizational
      climate of one public hospital and two private hospitals in Granada. The Work
      Environment Scale was used for data collection. The Work Environment Scale
      includes 10 scales, ranging from 0 to 9, which were used to evaluate social,
      demographic and organizational climate variables. In this study, 386 subjects
      were surveyed in three hospitals. RESULTS: A total of 87% of the participants
      were female and 16% were male. Most participants were nurses (65.6%), followed by
      nursing aides (20%), and technicians (14.4%). The results obtained reflected
      different patterns of organizational climate formation, based on hospital type
      (i.e. public or private) within the Spanish context. Most of the dimensions were
      below the midpoint of the scale. DISCUSSION AND CONCLUSIONS: In conclusion, in
      public hospitals, there is a greater specialization and the organizational
      climate is more salient than in the private hospitals. In addition, in the public
      hospitals, the characteristics of the human resources and their management can
      have a significant impact on the perception of the climate, which gives greater
      importance to the organizational climate as decisive of the ethical climate.

PMID- 24122763
TI  - Radiofrequency ablation for treatment of benign thyroid nodules: systematic
      review.
AB  - OBJECTIVE: To summarize the literature published to date on the use of
      radiofrequency ablation (RFA) in the treatment of benign thyroid nodules, to
      evaluate the effectiveness of this treatment, and to attempt an evaluation of
      factors that may influence treatment outcome. STUDY DESIGN: Systematic review
      with meta-analysis. METHODS: Systematic literature search was performed by two
      separate authors in four commonly used literature databases. Trials included in
      meta-analysis included only those presenting prospective data. Meta-analysis
      compared pretreatment values to post-treatment outcomes. RESULTS: Of 46 full-text
      articles identified, nine articles satisfied inclusion criteria. Two of these
      articles were randomized controlled trials comparing RFA to placebo or to some
      other treatment. One article was a randomized controlled trial comparing one RFA
      treatment to two treatments. The remaining six articles were noncontrolled,
      prospective observational studies. All analyzed outcomes showed statistically
      significant improvements from baseline to final follow-up, including reduction in
      nodule size, improvement of symptom and cosmetic scores, and withdrawal from
      methimazole. Improvement in nodule size remained significant in both "hot" and
      "cold" nodule subgroups. Twelve adverse events were identified across all studies
      out of 306 total treatments. Two of these events qualified as significant adverse
      events. None of these events resulted in hospitalization or death. CONCLUSIONS:
      Radiofrequency ablation is a safe and effective treatment for symptomatic thyroid
      nodules that are confirmed benign. However, the paucity of level 1 evidence
      comparing RFA to surgical or to other nonsurgical treatment modalities is
      concerning.

PMID- 24122764
TI  - Neutrophil-to-lymphocyte ratio as a predictor of outcomes for patients with
      hepatocellular carcinoma: a Western perspective.
AB  - BACKGROUND AND OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) is simple,
      inexpensive, and has been proposed to be predictive in hepatocellular carcinoma
      (HCC) in Europe and Asia. We aimed to evaluate whether NLR at presentation in a
      Western center provides any prognostic value compared to other common prognostic
      scores. METHODS: NLR was calculated for 75 consecutive patients at presentation
      with HCC and regression models were used to analyze its value for predicting
      treatment strategy and short-term survival with Child-Pugh and Model for End
      Stage Liver Disease (MELD). RESULTS: NLR was not predictive of future treatment
      regimens with hepatectomy, liver transplant, or transarterial chemoembolization
      (TACE; odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.71-1.02, P = 0.079)
      as compared the predictive value of MELD (OR: 0.81, CI: 0.72-0.93, P = 0.002) or
      Child-Pugh (OR: 0.48, CI: 0.34-0.69, P < 0.001). Adding additional adjustment for
      treatment, NLR did not correlate with short-term overall survival (hazard ratio
      [HR]: 1.09, CI: 0.95-1.24, P = 0.227). MELD also did not correlate with overall
      survival (HR: 1.04, CI: 0.96-1.13, P = 0.357) whereas Child-Pugh (HR: 1.56, CI:
      1.10-2.19, P = 0.011) was predictive. CONCLUSIONS: This study does not support
      the prognostic value of NLR to guide therapy for HCC in a Western center, whereas
      MELD and Child-Pugh score were more predictive.

PMID- 24122765
TI  - QuanPol: a full spectrum and seamless QM/MM program.
AB  - The quantum chemistry polarizable force field program (QuanPol) is implemented to
      perform combined quantum mechanical and molecular mechanical (QM/MM) calculations
      with induced dipole polarizable force fields and induced surface charge continuum
      solvation models. The QM methods include Hartree-Fock method, density functional
      theory method (DFT), generalized valence bond theory method, multiconfiguration
      self-consistent field method, Moller-Plesset perturbation theory method, and time
      dependent DFT method. The induced dipoles of the MM atoms and the induced surface
      charges of the continuum solvation model are self-consistently and variationally
      determined together with the QM wavefunction. The MM force field methods can be
      user specified, or a standard force field such as MMFF94, Chemistry at Harvard
      Molecular Mechanics (CHARMM), Assisted Model Building with Energy Refinement
      (AMBER), and Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA).
      Analytic gradients for all of these methods are implemented so geometry
      optimization and molecular dynamics (MD) simulation can be performed. MD free
      energy perturbation and umbrella sampling methods are also implemented.

PMID- 24122766
TI  - Ultrastructure of cisternal synapses on outer hair cells of the mouse cochlea.
AB  - C (cisternal) synapses with a near membrane postsynaptic cistern are found on
      motor neurons and other central neurons, where their functional role is unknown.
      Similarly structured cisternal synapses mediate cholinergic inhibition of
      cochlear hair cells via alpha9alpha10-containing ionotropic receptors and
      associated calcium-activated (SK2) potassium channels, providing the opportunity
      to examine the ultrastructure of genetically altered cisternal synapses. Serial
      section electron microscopy was used to examine efferent synapses of outer hair
      cells (OHCs) in mice with diminished or enhanced cholinergic inhibition. The
      contact area of efferent terminals, the appositional area of the postsynaptic
      cistern, the distance of the cistern from the plasma membrane, and the average
      width of the cisternal lumen were recorded. The synaptic cisterns of wild-type
      OHCs were closely aligned (14-nm separation) with the hair cell membrane and
      coextensive with the micrometers-long synaptic terminals. The cisternal lumen
      averaged 18 nm so that the cisternal volume was approximately 30% larger than
      that of the cytoplasmic space between the cistern and the plasma membrane.
      Synaptic ultrastructure of alpha9L9'T knockin OHCs (acetylcholine receptor gain
      of function) were like those of wild-type littermates except that cisternal
      volumes were significantly larger. OHCs of SK2 knockout mice had few small
      efferent terminals. Synaptic cisterns were present, but smaller than those of
      wild-type littermates. Taken together, these data suggest that the cistern serves
      as a sink or buffer to isolate synaptic calcium signals.

PMID- 24122768
TI  - Antimicrobial peptides against Pseudomonas syringae pv. actinidiae and Erwinia
      amylovora: Chemical synthesis, secondary structure, efficacy, and mechanistic
      investigations.
AB  - We report on structurally modified dodecapeptide amides (KYKLFKKILKFL-NH2) and
      two analogs of a hexapeptide amide (WRWYCR-NH2) with antibacterial activity
      against the Gram negative pathogens Pseudomonas syringae pv. actinidiae (Psa) and
      Erwinia amylovora (Ea). Dodecapeptide minimal inhibitory concentrations (MICs)
      ranged from 3.2 to 15.4 uM, with the unmodified peptide being the most potent
      against both pathogens. The unmodified dodecapeptide also had 32-58% alpha
      helicity in membrane mimetic environments (50% v/v trifluoroethanol and 30 mM SDS
      micelles). Structural modifications which included branching, acylation, and
      conjugation with 5-nitro-2-furaldehyde (NFA) proved detrimental to both
      antimicrobial activity and alpha-helicity. Scanning electron microscopy (SEM)
      revealed distinct morphological changes to bacterial cells treated with the
      different peptides, leading to blistering of the membrane and cell lysis. MICs of
      the hexapeptide amide were 3.9-7.7 uM against both pathogens. The hexapeptide
      acid did not show anti-bacterial activity against either pathogen. However, the
      NFA conjugated hexapeptide acid was more active than the parent peptide or NFA
      alone with MICs of 1.6-3.2 uM against the pathogens. SEM analysis revealed
      shriveling and collapse of bacterial cells treated with the hexapeptide, whereas
      shortening and compactness on exposure to streptomycin. A colorimetric assay
      demonstrated that the dodecapeptides were likely to act by targeting the
      bacterial membrane, whereas the hexapeptides, streptomycin, and NFA were not,
      thereby supporting the morphological changes observed during SEM. To the best of
      our knowledge, this appears to be the first report of antimicrobial peptide
      activity against Psa, a pathogen that is currently devastating the kiwifruit
      industry internationally.

PMID- 24122767
TI  - TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for
      first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2
      trial.
AB  - BACKGROUND: In patients with previously untreated metastatic colorectal cancer
      (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety,
      tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with
      conatumumab, an investigational, fully human monoclonal IgG1 antibody that
      specifically activates death receptor 5 (DR5). METHODS: Twelve patients were
      enrolled in a phase 1b open-label dose-escalation trial of conatumumab with
      mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive
      mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or
      placebo. Therapy cycles were repeated every 2 weeks until disease progression or
      the occurrence of unacceptable toxicity. RESULTS: In phase 1b, conatumumab with
      mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev
      alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in
      progression-free survival when compared with placebo with mFOLFOX6/bev. Toxicity
      was similar in all treatment arms. Following treatment, similar increases in
      circulating caspase-3 levels were observed in all arms. CONCLUSIONS: Conatumumab
      with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with
      placebo in first-line treatment of patients with mCRC. These data do not support
      further development of conatumumab in advanced CRC.

PMID- 24122769
TI  - Myb-independent macrophages: a family of cells that develops with their tissue of
      residence and is involved in its homeostasis.
AB  - In most metazoans, all tissues contain phagocytes "in residence," generally
      termed "macrophages" in vertebrates. In contrast to myeloid cells produced
      continuously by the bone marrow (BM), tissue-resident macrophages develop during
      embryogenesis together with their tissue of residence, and persist in adulthood,
      independently of hematopoietic stem cells and the transcription factor Myb. They
      therefore represent an independent lineage from blood monocytes, dendritic cells,
      and monocytes/macrophages that are recruited to tissues during inflammation.
      Tissue-resident macrophage functions are yet to be completely defined. They all
      share the ability to scavenge toxic compounds, lipids, microorganisms, and dead
      cells and contribute to tissue remodeling, via phagocytosis and the production of
      growth factors. In contrast, the production of inflammatory mediators seems to be
      more associated with BM-derived cells. Tissue-resident macrophages and BM-derived
      myeloid cells thus differ in developmental origin and functions; the term
      "macrophages" could be reserved for Myb-independent-resident macrophages to avoid
      confusion. A genetic and molecular dissection of resident macrophage functions
      will reveal their roles in tissue metabolism and the maintenance of homeostasis
      independently of the extravasation of inflammatory leukocytes, and in the control
      of the recruitment of BM-derived cells in overt inflammation. 

PMID- 24122770
TI  - Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case-control study
      of colorectal cancer in UK collaborative trial of ovarian cancer screening.
AB  - Recent reports suggest that autoantibodies directed to aberrantly glycosylated
      mucins, in particular MUC1 and MUC4, are found in patients with colorectal
      cancer. There is, however, limited information on the autoantibody levels before
      clinical diagnosis, and their utility in cancer screening in the general
      population. In our study, we have generated O-glycosylated synthetic MUC1 and
      MUC4 peptides in vitro, to mimic cancer-associated glycoforms, and displayed
      these on microarrays. The assay's performance was tested through an initial
      screening of serum samples taken from patients at the time of colorectal cancer
      diagnosis and healthy controls. Subsequently, the selected biomarkers were
      evaluated in a blinded nested case-control study using stored serum samples from
      among the 50,640 women randomized to the multimodal arm of the UK Collaborative
      Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood
      samples for several years. Cases were 97 postmenopausal women who developed
      colorectal cancer after recruitment and were age-matched to 97 women without any
      history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases
      with 8.2 and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4
      glycoforms were unable to discriminate between cases and controls in the UKCTOCS
      sera. Additional analysis was undertaken by combining the data of MUC1-STn and
      MUC1-Core3 with previously generated data on autoantibodies to p53 peptides,
      which increased the sensitivity to 32.0% at 95% specificity. These findings
      suggest that a combination of antibody signatures may have a role as part of a
      biomarker panel for the early detection of colorectal cancer.

PMID- 24122771
TI  - Monitoring of nitrites and nitrates levels in leafy vegetables (spinach and
      lettuce): a contribution to risk assessment.
AB  - BACKGROUND: Nitrites and nitrates are compounds considered harmful to humans and
      the major part of the daily intake of nitrates in foodstuffs is related to
      vegetable consumption. In this work, 150 leafy vegetables samples (75 spinach and
      75 lettuce) were analysed in order to assess the levels of nitrites and nitrates.
      The analyses were carried out by a validated ion chromatography method and the
      samples with nitrate concentrations higher than legal limits and/or with
      quantifiable concentrations of nitrites were confirmed by an alternative ion
      chromatography method. RESULTS: Nitrate levels higher than legal limits were
      detected both in spinach (four samples) and in lettuce (five samples). Nitrite
      residues were registered both at low concentrations--lower than 28.5 mg kg-1 (12
      spinach samples)--and at high concentrations, up to 197.5 mg kg-1 (three spinach
      and one lettuce sample). CONCLUSION: Considering the non-negligible percentage of
      'not-compliant' samples for nitrates (6.0%), control is needed. Moreover, it is
      possible to suggest the introduction in the Communities Regulations of a 'maximum
      admissible level' for nitrites in leafy vegetables.

PMID- 24122773
TI  - A preliminary report of percutaneous craniofacial osteoplasty in a rat calvarium.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the potential for injectable, permanent bone
      augmentation by assessing the biocompatability and bioactivity of subperiosteal
      hydroxylapatite (Radiesse) deposition in a rat model. STUDY DESIGN: Randomized
      controlled animal model. METHODS: Fourteen adult Sprague Dawley rats were
      injected in the parietal skull with 0.2 ml of hydroxylapatite (10 animals) or 0.2
      ml of a carrier gel control (4 animals), using a subperiosteal injection
      technique on the right and a subcutaneous injection technique on the left. At 1,
      3, and 6 months, three rats (1 negative control, 2 variables) were sacrificed and
      the calvaria were harvested. At 12 months, the remaining five rats were
      sacrificed. After each harvest, the specimens were processed and then examined
      under both light and polarized microscopy for new bone growth at the injection
      sites. RESULTS: The inflammatory response was limited with both hydroxylapatite
      and carrier injections. Injectables were still present 12 months after the
      injection. New bone formation was only observed when the injection was located
      deep to a disrupted periosteum The odds of new bone formation was 48.949 times
      higher (95% confidence intervals CI [2.637, 3759.961]; P=0.002) with
      subperiosteal hydroxylapatite injections compared to all other combinations of
      injection plane and injectable. CONCLUSIONS: This preliminary report of
      subperiosteal hydroxylapatite (Radiesse) injection in a rat model has verified
      the biocompatibility of injectable hydroxylapatite at the bony interface and
      suggests the potential for new bone formation. LEVEL OF EVIDENCE: N/A.

PMID- 24122772
TI  - Role of exercise in maintaining the integrity of the neuromuscular junction.
AB  - Physical activity plays an important role in preventing chronic disease in adults
      and the elderly. Exercise has beneficial effects on the nervous system, including
      at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and
      improves recovery from peripheral nerve injuries, whereas decreased physical
      activity causes degenerative changes in NMJs. Recent studies have begun to
      elucidate molecular mechanisms underlying the beneficial effects of exercise.
      These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated
      receptor gamma coactivator 1alpha, insulin-like growth factor-1, glial cell line
      derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of
      activated T cells c1. For example, NMJ denervation and active zone decreases have
      been observed in aged NMJs, but these age-dependent degenerative changes can be
      ameliorated by exercise. In this review we assess the effects of exercise on the
      maintenance and regeneration of NMJs and highlight recent insights into the
      molecular mechanisms underlying these exercise effects.

PMID- 24122774
TI  - Minimum reporting standards for copers in chronic ankle instability research.
AB  - Lateral ankle sprains (LASs) are among the most common sports-related injuries
      and a high percentage of individuals who sprain their ankle go on to develop
      chronic ankle instability (CAI). The condition of CAI is often classified as
      having pain, loss of function, and a restriction of, or failure to, return to
      levels of previous activity. Historically, uninjured healthy controls are used as
      a comparison group to study the biomechanical and neuromuscular consequences of
      CAI. However, this model is not ideal to determine why a portion of the
      population experiencing an ankle sprain does not recover. A more appropriate
      comparison may be individuals who had an ankle sprain, and thus the exposure, but
      did not go on to develop CAI (i.e., copers). Thus, the purpose of this review was
      to determine the existing discrepancies and common standards in definitions of,
      terminology used for, and the inclusionary/exclusionary criteria used to describe
      copers within the CAI literature. Multiple databases were searched by keywords
      and specific authors. Potential studies were screened independently by both
      authors. Inclusion criteria consisted of an explicit definition of copers and
      explicit inclusionary/exclusionary criteria. A total of 21 studies were included
      in the current study and had four outcomes extracted: (1) the definition of
      copers; (2) the terminology used; (3) specific inclusionary/exclusionary
      criteria; and (4) injury characteristics of the copers. Based on the included
      operational definitions, it is recommend that future operational definitions of
      copers include three key components: (1) an initial LAS; (2) subsequent lack of
      CAI symptoms (i.e., no complaints of disability or giving way); and (3) a time
      since injury component. The term coper was overwhelming used within the existing
      literature (n = 15) and is thus recommended to be used in future studies when
      describing individuals who have suffered an LAS but failed to develop CAI.
      Minimal inclusionary criteria should consist of three things: (1) an initial LAS
      severe enough to warrant either the use of a protective device (e.g., ankle
      brace) for at least 1 week or immobilization and/or non-weight bearing for at
      least 3 days, or both; (2) a return to at least moderate levels of weight-bearing
      physical activity for at least 12 months without recurrent injury, episodes of
      giving way, and/or feelings of instability; and (3) minimal, if any, level of
      self-reported disability. Acute head and/or lower extremity injuries that
      occurred <=3 months prior to testing, a history of ankle fractures and/or
      surgeries, and the presence of pain (constant or intermittent) should be used as
      minimal exclusionary criteria in future investigations dealing with copers.
      Finally, at least seven items should be reported to better contextualize copers
      across investigations. These items should include the initial mechanism of
      injury, the presence of mechanical laxity, number of days immobilized and/or non
      weight bearing after the initial ankle sprain, time since the latest ankle
      sprain, percentage of coper participants with a recurrent ankle sprain or giving
      way episode, current physical activity levels, and whether copers attended formal
      rehabilitation for their involved ankle.

PMID- 24122776
TI  - A drug and disease model for lixisenatide, a GLP-1 receptor agonist in type 2
      diabetes.
AB  - Incretin hormone analogs such as glucagon-like peptide-1 (GLP-1) receptor
      agonists have emerged as promising new options for the treatment of type 2
      diabetes mellitus (T2DM), targeting several of its pathophysiological traits,
      including reduced insulin sensitivity, inadequate insulin secretion, and loss of
      beta-cell mass (BCM). This article describes the semi-mechanistic modeling of
      lixisenatide dose-response over time using fasting plasma glucose (FPG), fasting
      serum insulin (FSI) and glycated hemoglobin (HbA1c) data from two Phase II and
      four Phase III clinical trials, for a total of 2470 T2DM patients. Previously
      published models for FPG, FSI, and BCM as well as HbA1c were adapted and expanded
      to describe the available data. The model incorporated aspects describing disease
      progression, standard-of-care, FPG-dependent and -independent HbA1c synthesis,
      and covariate effects of body size, race, and sex. The final model described
      lixisenatide effects on beta-cell responsiveness, insulin sensitivity and FPG
      independent HbA1c synthesis, was able to describe the observed FPG, FSI, and
      HbA1c data accurately, and was successful in predicting data from an unseen Phase
      III clinical study. 

PMID- 24122775
TI  - Do school-based interventions focusing on physical activity, fitness, or
      fundamental movement skill competency produce a sustained impact in these
      outcomes in children and adolescents? A systematic review of follow-up studies.
AB  - OBJECTIVE: The aim of this systematic review was to determine whether typically
      developing children and adolescents (aged 3-18 years) who have participated in
      school-based interventions have sustained outcomes in PA, fitness, and/or FMS.
      METHODS: A systematic search of six electronic databases (CINAHL(r) Plus with
      Full Text, Ovid MEDLINE(r), SPORTDiscusTM, Scopus, PsycINFO(r) and ERIC) was
      conducted from 1995 to 26 July 2012. Included studies were school-based studies
      (including randomized controlled trials, longitudinal cohort, quasi-experimental,
      and experimental) that had a positive effect at post intervention in at least one
      variable and had a follow-up PA, fitness, or FMS assessment at least 6 months
      after the post-intervention assessment. Risk of bias assessment was guided by the
      "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" statement.
      RESULTS: The search identified 14 articles, and some studies addressed multiple
      outcomes: 13 articles assessed PA; three assessed fitness; and two assessed FMS.
      No study in this review met four key methodological criteria that have been shown
      to influence results, i.e., clarity on the randomization process, assessor
      blinding, analyzing participants in their original groups, and retaining
      sufficient participants through the entire study. Three-quarters (ten of 13) of
      the studies addressing PA, reported PA behavior change maintenance. The length of
      follow-up ranged from 6 months to 20 years, and the degree of PA difference
      reported was between 3 and 14 min per day. Only one of the three studies
      assessing fitness reported a sustained impact, whilst both studies that assessed
      FMS reported maintenance of effects. CONCLUSION: It is likely that PA is a
      sustainable outcome from interventions in children and adolescents, and there is
      reasonable evidence that interventions of longer than 1 year and interventions
      that utilize a theoretical model or framework are effective in producing this
      sustained impact. It would seem probable that FMS are a sustainable outcome in
      children and adolescents; however, this finding should be viewed with caution
      given the lack of studies and the risk of bias assessment. More research is
      needed to assess the sustainability of fitness interventions as this review only
      included a handful of studies that addressed fitness and only one of these
      studies found a sustained impact.

PMID- 24122777
TI  - CD81 sequence and susceptibility to hepatitis C infection.
AB  - Several cell surface molecules have hepatitis C virus (HCV) binding properties
      and may serve as receptors facilitating viral entry into cells. The large
      extracellular loop (LEL) of CD81 has been shown to bind the HCV envelope protein
      E2 with several critical residues for the CD81-HCV-E2 interaction. It was
      hypothesised that variation in the CD81 LEL sequence may modify susceptibility to
      HCV infection. HCV RNA negative patients with spontaneous viral clearance (RNA 
      ve); HCV RNA positive cases, who are affected chronically (RNA +ve); and patients
      at high risk of HCV infection, exposed but uninfected patients (EU) were studied.
      Genomic DNA was extracted from whole blood samples and four exons of the CD81 LEL
      gene were amplified by PCR and sequenced. The cDNA derived from CD81 (~700 bp)
      was sequenced following RNA extraction from peripheral blood mononuclear cells.
      Patients, who are RNA positive, RNA negative, and exposed uninfected were
      sequenced for four DNA sections (A, B, C, and D). Sixty-two (43M:19F) patients,
      from all the patient cohorts, were sequenced and compared for the C section alone
      (which encompasses the important binding region of the molecule for envelope
      protein) including 21 (14M:7F) HCV RNA negative, 15 (10M:5F) HCV RNA positive and
      26 (20M:6F) exposed uninfected and no sequence differences were observed. The
      entire CD81 sequence from cDNA was obtained in 23 cases-11 RNA -ve, 5 RNA +ve and
      7 EU. In 7 of the 23 cases, the nucleotides were confirmed with the genomic
      sequence (4 RNA -ve and 3 EU cases). No sequence variation was found in any of
      the patients studied by either method, including gene sections encoding the
      residues most important for CD81-HCV E2 binding. The LEL of CD81 is a molecule
      that is highly conserved. No differences in nucleotide sequence influencing
      susceptibility to, or outcome of HCV infection or evidence of methylation of the
      gene were found.

PMID- 24122778
TI  - Thyroid metastasectomy.
AB  - Metastases to the thyroid gland are uncommon. Renal, lung, breast, and colon
      cancer and melanoma are the most common primary diseases implicated. Few
      retrospective series have been reported. Treatment decisions must be
      individualized, and will depend on the state of systemic disease. Selected
      patients could benefit from surgical treatment. Although most patients selected
      for surgery will not be cured, the aim of surgery is to avoid the complications
      of uncontrolled central neck disease.

PMID- 24122779
TI  - Subglottic stenosis: a ten-year review of treatment outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the endoscopic surgical management of adult
      subglottic stenosis and describe treatment outcomes. STUDY DESIGN: Retrospective
      review. METHODS: Ten-year review of adult patients with subglottic stenosis.
      RESULTS: Ninety-two adults (23 male, 69 female) with subglottic stenosis
      underwent 247 endoscopic dilations between 2001 and 2010. The mean age was 48
      years at time of first surgery. Etiology was GPA (granulomatosis with
      polyangiitis, formerly Wegener's granulomatosis) (45%), intubation (25%), or
      idiopathic (33%). Forty-one patients (45%) underwent a single procedure; 51
      patients (55%) required multiple surgeries. The average interval for patients
      requiring a subsequent procedure was 13.7 months. Variations in surgical
      technique did not show differences in time to next procedure, and the use of
      mitomycin-C did not result in longer intervals between procedures. No significant
      complications were encountered after dilation. CONCLUSIONS: Subglottic stenosis
      remains a treatment challenge. Although patients are often symptomatically
      improved after endoscopic dilation, recurrence rates remain high.

PMID- 24122780
TI  - Comparison of the capillary wave method and pressure tensor route for calculation
      of interfacial tension in molecular dynamics simulations.
AB  - We have studied the calculation of surface and interfacial tension for a variety
      of liquid-vapor and liquid-liquid interfaces using molecular dynamics (MD)
      simulations. Because of the inherently small scale of MD systems, large pressure
      fluctuations can cause imprecise calculations of surface tension using the
      pressure tensor route. The capillary wave method exhibited improved precision and
      stability throughout all of the simulated systems in this study. In order to
      implement this method, the interface was defined by fitting an error function to
      the density profile. However, full mapping of the interface from coordinate files
      produced enhanced accuracy. Upon increasing the system size, both methods
      exhibited higher precision, although the capillary wave method was still more
      reliable.

PMID- 24122781
TI  - Identification of dosage-sensitive genes in fetuses referred with severe isolated
      congenital diaphragmatic hernia.
AB  - OBJECTIVE: Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting
      diaphragm and lung development with a high mortality rate despite advances in
      fetal and neonatal therapy. CDH may occur either as an isolated defect or in
      syndromic form for which the prognosis is worse. Although conventional
      karyotyping and, more recently, chromosomal microarrays support a substantial
      role for genetic factors, causal genes responsible for isolated CDH remain
      elusive. We propose that chromosomal microarray analysis will identify copy
      number variations (CNVs) associated with isolated CDH. METHODS: We perform a
      prospective genome-wide screen for CNVs using chromosomal microarrays on 75
      fetuses referred with apparently isolated CDH, six of which were later
      reclassified as non-isolated CDH. RESULTS: The results pinpoint
      haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations.
      In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with
      isolated CDH. By using gene prioritisation and network analysis, we provide
      strong evidence for several novel dosage-sensitive candidate genes associated
      with CDH. CONCLUSIONS: Chromosomal microarray analysis detects submicroscopic
      CNVs associated with isolated CDH or CDH with cardiovascular malformations.

PMID- 24122782
TI  - Surgical management of metastatic tumors.

PMID- 24122783
TI  - Scutellaria polysaccharide inhibits the infectivity of Newcastle disease virus to
      chicken embryo fibroblast.
AB  - BACKGROUND: To select the antiviral active site of Scutellaria polysaccharide
      (SPS), safe concentrations of crude total Scutellaria polysaccharide (SPS(t)) and
      fractional polysaccharide SPS50, SPS60, SPS70 and SPS80 on chicken embryo
      fibroblast (CEF) were first compared using the MTT method. Then, SPS(t), SPS50,
      SPS60, SPS70, and SPS80 at five concentrations within the safe concentration,
      together with Newcastle disease virus (NDV), were added to the cultivating system
      of CEF in three models: pre-addition of polysaccharide, post-addition of
      polysaccharide, and simultaneous addition of polysaccharides and NDV after
      mixing. The effects of SPS on the cellular infectivity of NDV (A570 value and the
      highest viral inhibitory rate) were compared using the MTT method. RESULTS: At
      appropriate concentrations, the five polysaccharides could significantly inhibit
      the infectivity of NDV on CEF. Among the five polysaccharide groups, the SPS80
      group exhibited the highest viral inhibitory rate in the three sample-addition
      modes. CONCLUSION: This finding indicates that SPS80 possesses the best efficacy
      as a component of antiviral polysaccharide drug.

PMID- 24122784
TI  - Associations among prognostic understanding, quality of life, and mood in
      patients with advanced cancer.
AB  - BACKGROUND: Patients' perception of their prognosis has an impact on their
      decisions about medical care. However, the relations between prognostic
      understanding and quality of life (QoL) and mood are unknown. The objectives of
      this study were to assess perceptions of prognosis and preferences for prognostic
      information among patients with advanced cancer and to explore the associations
      of prognostic understanding with QoL and mood. METHODS: Fifty patients were
      assessed within 6 to 12 weeks of initiating chemotherapy for advanced
      gastrointestinal cancers. A 13-item questionnaire was used to assess patients'
      information preferences, perceptions of their prognosis and goal of therapy, and
      communication about end-of-life care. The Functional Assessment of Cancer Therapy
      General and the Hospital Anxiety and Depression Scale were used to assess QoL and
      mood, respectively. RESULTS: Fifty of 62 (80%) consecutive, eligible patients
      were enrolled. Thirty-eight of 50 patients (75%) wanted to know as many details
      as possible about their cancer diagnosis and treatment. However, 25 of 50
      patients (50%) stated that the goal of therapy was to "cure their cancer," and
      only 10 of 49 patients (22%) reported having a discussion about end-of-life
      preferences with their oncologist. Patients who acknowledged their illness as
      terminal reported lower QoL (P=.005) and higher anxiety (P=.003) compared with
      those who did not perceive themselves as being terminally ill. CONCLUSIONS:
      Although patients desired detailed information about their illness, half
      incorrectly perceived their cancer as curable. Accurate prognostic understanding
      was associated with lower QoL and worse anxiety. Interventions to improve
      patients' prognostic understanding while providing adequate psychosocial support
      are warranted.

PMID- 24122785
TI  - Serine protease identification (in vitro) and molecular structure predictions (in
      silico) from a phytopathogenic fungus, Alternaria solani.
AB  - Serine proteases are involved in an enormous number of biological processes. The
      present study aims at characterizing three-dimensional (3D) molecular
      architecture of serine proteases from early blight pathogen, Alternaria solani
      that are hypothesized to be markers of phytopathogenicity. A serine protease was
      purified to homogeneity and MALDI-TOF-MS/MS analysis revealed that protease
      produced by A. solani belongs to alkaline serine proteases (AsP). AsP is made up
      of 403 amino acid residues with molecular weight of 42.1 kDa (Isoelectric point -
      6.51) and its molecular formula was C1859 H2930 N516 O595 S4 . AsP structure
      model was built based on its comparative homology with serine protease using the
      program, MODELER. AsP had 16 beta-sheets and 10 alpha-helices, with Ser(350)
      (G347-G357), Asp(158) (D158-H169), and His(193) (H193-G203) in separate turn/coil
      structures. Biological metal binding region situated near 6th-helix and His(193)
      residue is responsible for metal binding site. Also, calcium ion (Ca(2+)) is
      coordinated by the carboxyl groups of Lys(84), Ile(85), Lys(86), Asp(87),
      Phe(88), Ala(89), Ala(90) (K84-A90) for first Ca(2+) binding site and carbonyl
      oxygen atom of Lys(244), Gly(245), Arg(246), Thr(247), Lys(248), Lys(249), and
      Ala(250) (K244-A250), for second Ca(2+) binding site. Moreover, Ramachandran plot
      analysis of protein residues falling into most favored secondary structures were
      determined (83.3%). The predicted molecular 3D structural model was further
      verified using PROCHECK, ERRAT, and VADAR servers to confirm the geometry and
      stereo-chemical parameters of the molecular structural design. The functional
      analysis of AsP 3D molecular structure predictions familiar in the current study
      may provide a new perspective in the understanding and identification of
      antifungal protease inhibitor designing.

PMID- 24122786
TI  - Pharyngotracheal fistula closure using the internal mammary artery perforator
      island flap.
AB  - OBJECTIVES/HYPOTHESIS: Salvage laryngectomy following organ preservation therapy
      is a frequent condition that exposes patients to pharyngocutaneous and
      pharyngotracheal fistulas. Definitive treatment frequently requires well
      vascularized tissue harvested from the chest. To limit tracheostoma obstruction,
      a thin and pliable flap is preferable. The internal mammary artery perforator
      (IMAP) island flap fulfills these criteria, but it is not well known and is not
      commonly used by head and neck surgeons. In this article, based on our
      experience, we describe our surgical technique and the strengths and weaknesses
      of this flap. STUDY DESIGN: Retrospective cohort study and systematic review of
      the literature. METHODS: An IMAP flap was performed on 12 patients to repair
      postoperative fistulas, located in the lower neck close to the tracheal stoma or
      involving the posterior tracheal wall, from March 2009 to December 2012. The
      medical records of each of patient were retrospectively analyzed. RESULTS: A
      breach of the pleura occurred in one patient. It was diagnosed and treated
      perioperatively. One patient had a total flap necrosis and required a
      reoperation. The postoperative course was uneventful in 11 patients (92%). All
      donor sites were closed primarily without any wound-healing problems.
      CONCLUSIONS: The IMAP flap is reliable. Its advantages make it a convenient flap
      to repair peritracheostomal defects and fistulas. The harvesting technique is not
      very demanding but requires training.

PMID- 24122787
TI  - Determination of rhynchophylline and hirsutine in rat plasma by UPLC-MS/MS after
      oral administration of Uncaria rhynchophylla extract.
AB  - An ultra-performance liquid chromatography with tandem mass spectrometry (UPLC
      MS/MS) method was developed and validated to concurrently determine
      rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma
      was achieved by alkalization and liquid-liquid extraction. The mass transition of
      precursor ion -> product ion pairs were monitored at m/z 385.2 -> 160.0 for
      rhynchophylline, m/z 369.3 -> 144.0 for hirsutine and m/z 414.0 -> 220.0 for
      noscapine (internal standard). This method revealed linear relationships from 2.5
      to 50 ng/mL (r(2)  > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r(2)  >
      0.998) for hirsutine. The limit of quantification values for rhynchophylline and
      hirsutine in rat plasma were both 2.5 ng/mL. Intra-day and inter-day precisions
      were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and
      the accuracy (bias) was <10%. Liquid-liquid extraction of rat plasma samples
      resulted in insignificant matrix effect, and the extraction recoveries were
      >83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal
      standard. This method was applied successfully to a pharmacokinetic study of
      rhynchophylline and hirsutine in rats after oral administration.

PMID- 24122788
TI  - De novo partial deletion in GRID2 presenting with complicated spastic paraplegia.
AB  - INTRODUCTION: Complex forms of spastic paraplegia (SPG) are rare and genetically
      heterogeneous. In apparently sporadic cases, analysis of known SPG genes often
      fails to reveal a mutation. METHODS: We report a 24-year-old patient with a
      syndrome of spastic paraplegia, ataxia, frontotemporal dementia, and lower motor
      neuron involvement. RESULTS: Screening of the patient's genome for copy number
      variation identified a novel 276 kb deletion spanning the first exon of the GRID2
      gene. MRI scan showed atrophy of the cerebellum, and electromyography revealed a
      chronic disorder of motor neurons or their axons. A deletion in GRID2, coding for
      the glutamate receptor delta-2 subunit precursor protein, was excluded in either
      parent, suggesting that the deletion in the index patient occurred de novo.
      CONCLUSIONS: We hypothesize that the deletion identified here is the cause of our
      patient's clinical presentation, due to the resemblance to the GRID2 mutation
      phenotype in mouse models.

PMID- 24122789
TI  - The perforation technique: a modification to the frontal sinus osteoplastic flap.

PMID- 24122790
TI  - A reporter assay for the next generation of biomaterials: porous-wall hollow
      glass microspheres.
AB  - OBJECTIVES/HYPOTHESIS: The primary objective was to design a reporter assay to
      measure molecular release kinetics from a new porous-wall hollow glass
      microsphere biomaterial with great potential in regenerative medicine and drug
      delivery. Second, future avenues for research will be discussed specifically in
      regard to potential clinical uses in laryngology. STUDY DESIGN: Basic science
      data report. METHODS: We developed an assay using fluorescent nanocrystals or
      quantum dots (Qdot 605) as a reporter. A Nuance FX multispectral imaging system
      was used to detect fluorescence in aqueous phase. Spectral output of known
      concentrations of aqueous Qdot 605 was measured by the Nuance system to create a
      standard curve. RESULTS: These data were plotted and fit to a curve. Qdot 605
      emission demonstrates excellent correlation with concentration in a log-log
      relationship [R(2) = 0.99649, median error = 9.9%], indicating that the Qdot 605
      assay is reliable and should be explored regarding its ability to evaluate the
      drug-eluting properties of this material. CONCLUSIONS: We have derived a method
      to measure Qdot concentration using fluorescent microscopy, which will facilitate
      future research on this exciting new biomaterial. This material has great
      potential for use in head and neck surgery. Specific avenues within laryngology
      to be investigated include laryngeal and tracheal reconstruction, vocal fold
      healing, and nerve regeneration. Furthermore, we believe this is the first
      documented use of the Nuance system to determine aqueous molecular
      concentrations. LEVEL OF EVIDENCE: NA.

PMID- 24122791
TI  - Poor concordance among nine immunohistochemistry classifiers of cell-of-origin
      for diffuse large B-cell lymphoma: implications for therapeutic strategies.
AB  - PURPOSE: The opportunity to improve therapeutic choices on the basis of molecular
      features of the tumor cells is on the horizon in diffuse large B-cell lymphoma
      (DLBCL). Agents such as bortezomib exhibit selective activity against the poor
      outcome activated B-cell type (ABC) DLBCL. In order for targeted therapies to
      succeed in this disease, robust strategies that segregate patients into molecular
      groups with high reliability are needed. Although molecular studies are
      considered gold standard, several immunohistochemistry (IHC) algorithms have been
      published that claim to be able to stratify patients according to their cell-of
      origin and to be relevant for patient outcome. However, results are poorly
      reproducible by independent groups. EXPERIMENTAL DESIGN: We investigated nine IHC
      algorithms for molecular classification in a dataset of DLBCL diagnostic
      biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1,
      and LMO2. IHC profiles were assessed and agreed among three expert observers. A
      consensus matrix based on all scoring combinations and the number of subjects for
      each combination allowed us to assess reliability. The survival impact of
      individual markers and classifiers was evaluated using Kaplan-Meier curves and
      the log-rank test. RESULTS: The concordance in patient's classification across
      the different algorithms was low. Only 4% of the tumors have been classified as
      germinal center B-cell type (GCB) and 21% as ABC/non-GCB by all methods. None of
      the algorithms provided prognostic information in the R-CHOP (rituximab plus
      cyclophosphamide-adriamycin-vincristine-prednisone)-treated cohort. CONCLUSION:
      Further work is required to standardize IHC algorithms for DLBCL cell-of-origin
      classification for these to be considered reliable alternatives to molecular
      based methods to be used for clinical decisions.

PMID- 24122792
TI  - ECOG phase II trial of graded-dose peginterferon alpha-2b in patients with
      metastatic melanoma overexpressing basic fibroblast growth factor (E2602).
AB  - PURPOSE: We investigated the use of graded-dose peginterferon alpha-2b (Peg-IFN)
      in patients with stage IV melanoma overexpressing basic fibroblast growth factor
      (FGF-2). The primary objective was suppression of plasma FGF-2 to within
      reference range (<= 7.5 pg/mL). EXPERIMENTAL DESIGN: Plasma FGF-2 was measured at
      baseline (step 1), and patients with concentrations of 15 pg/mL or more were
      eligible for study treatment (step 2). Peg-IFN was given weekly at a starting
      dose of 0.5 MUg/kg/wk with increment every 3 weeks based on serial FGF-2
      concentrations. RESULTS: Two hundred seven patients entered step 1; 45 (22%)
      overexpressed FGF-2 (median = 22 pg/dL). Twenty-nine eligible patients entered
      step 2 and received treatment. Patients' median age was 64 years (range, 29-84
      years). Most had more than two prior therapies. FGF-2 decreased in 28 (97%)
      patients, with suppression to reference range in 10 (35%). Median time to FGF-2
      suppression was 30 days. The best clinical responses were partial response (7%)
      and stable disease (17%). Median progression-free survival (PFS) and overall
      survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2
      suppression were more likely than those who did not to have a response or stable
      disease (P = 0.03). VEGF concentrations decreased in 27 patients (93%) during
      treatment and paralleled those of FGF-2 over time. We found no compensatory
      increase in VEGF among those with FGF-2 suppression. CONCLUSIONS: Graded-dose Peg
      IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2.
      Over one third of patients had complete suppression of plasma FGF-2, which
      correlated with clinical response to this therapy.

PMID- 24122793
TI  - Increased TGF-alpha as a mechanism of acquired resistance to the anti-EGFR
      inhibitor cetuximab through EGFR-MET interaction and activation of MET signaling
      in colon cancer cells.
AB  - PURPOSE: Although cetuximab, an anti-EGF receptor (EGFR) monoclonal antibody, is
      an effective treatment for patients with KRAS wild-type metastatic colorectal
      cancer (mCRC), its clinical use is limited by onset of resistance. EXPERIMENTAL
      DESIGN: We characterized two colorectal cancer models to study the mechanisms of
      acquired resistance to cetuximab. RESULTS: Following chronic treatment of nude
      mice bearing cetuximab-sensitive human GEO colon xenografts, cetuximab-resistant
      GEO (GEO-CR) cells were obtained. In GEO-CR cells, proliferation and survival
      signals were constitutively active despite EGFR inhibition by cetuximab
      treatment. Whole gene expression profiling identified a series of genes involved
      in the hepatocyte growth factor (HGF)-MET-dependent pathways, which were
      upregulated in GEO-CR cells. Furthermore, activated, phosphorylated MET was
      detected in GEO-CR cells. A second colorectal cancer cell line with acquired
      resistance to cetuximab was obtained (SW48-CR). Inhibition of MET expression by
      siRNA restored cetuximab sensitivity in GEO-CR and SW48-CR cells, whereas
      exogenous activation of MET by HGF stimulation in cetuximab-sensitive GEO and
      SW48 cells induced resistance to cetuximab. Treatment of GEO-CR and SW48-CR cells
      with PHA665752, a selective MET inhibitor, inhibited cell growth, proliferation,
      and survival signals and impaired cancer cell migration. Overexpression of TGF
      alpha, a specific EGFR ligand, was involved in the acquisition of cetuximab
      resistance in GEO-CR and SW48-CR cells. In fact, TGF-alpha overexpression induced
      the EGFR-MET interaction, with subsequent MET phosphorylation and activation of
      MET downstream effectors in GEO-CR and SW48-CR cells. CONCLUSIONS: These results
      suggest that overexpression of TGF-alpha through induction of EGFR-MET
      interaction contributes to cetuximab resistance in colorectal cancer cells. The
      combined inhibition of EGFR and MET receptor could represent a strategy for
      preventing and/or overcoming cetuximab resistance in patients with colorectal
      cancer.

PMID- 24122794
TI  - Autotaxin-lysophosphatidic acid signaling axis mediates tumorigenesis and
      development of acquired resistance to sunitinib in renal cell carcinoma.
AB  - PURPOSE: Sunitinib is currently considered as the standard treatment for advanced
      renal cell carcinoma (RCC). We aimed to better understand the mechanisms of
      sunitinib action in kidney cancer treatment and in the development of acquired
      resistance. EXPERIMENTAL DESIGN: Gene expression profiles of RCC tumor
      endothelium in sunitinib-treated and -untreated patients were analyzed and
      verified by quantitative PCR and immunohistochemistry. The functional role of the
      target gene identified was investigated in RCC cell lines and primary cultures in
      vitro and in preclinical animal models in vivo. RESULTS: Altered expression of
      autotaxin, an extracellular lysophospholipase D, was detected in sunitinib
      treated tumor vasculature of human RCC and in the tumor endothelial cells of RCC
      xenograft models when adapting to sunitinib. ATX and its catalytic product,
      lysophosphatidic acid (LPA), regulated the signaling pathways and cell motility
      of RCC in vitro. However, no marked in vitro effect of ATX-LPA signaling on
      endothelial cells was observed. Functional blockage of LPA receptor 1 (LPA1)
      using an LPA1 antagonist, Ki16425, or gene silencing of LPA1 in RCC cells
      attenuated LPA-mediated intracellular signaling and invasion responses in vitro.
      Ki16425 treatment also dampened RCC tumorigenesis in vivo. In addition,
      coadministration of Ki16425 with sunitinib prolonged the sensitivity of RCC to
      sunitinib in xenograft models, suggesting that ATX-LPA signaling in part mediates
      the acquired resistance against sunitinib in RCC. CONCLUSIONS: Our results reveal
      that endothelial ATX acts through LPA signaling to promote renal tumorigenesis
      and is functionally involved in the acquired resistance of RCC to sunitinib.

PMID- 24122795
TI  - Molecular pathways: SWI/SNF (BAF) complexes are frequently mutated in cancer-
      mechanisms and potential therapeutic insights.
AB  - SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular
      machines that utilize the energy of ATP hydrolysis to modulate chromatin
      structure. The complexes interact with transcription factors at promoters and
      enhancers to modulate gene expression and contribute to lineage specification,
      differentiation, and development. Initial clues to a role in tumor suppression
      for SWI/SNF complexes came over a decade ago when the gene encoding the
      SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all
      pediatric rhabdoid tumors. In the last three years, cancer-genome sequencing
      efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit
      genes, which are collectively mutated in 20% of all human cancers and approach
      the frequency of p53 mutations. Here, we provide a background on these newly
      recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor
      suppressor activity, and highlight findings that may lead to potential
      therapeutic targets for SWI/SNF-mutant cancers.

PMID- 24122797
TI  - Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in
      subjects with hepatic or renal impairment.
AB  - Macitentan is under development for the treatment of pulmonary arterial
      hypertension (PAH). Patients with PAH may suffer from comorbidities such as renal
      or hepatic impairment. Two prospective, single-center, open-label studies
      evaluated the pharmacokinetics of macitentan and its metabolites
      (pharmacologically active ACT-132577 and inactive ACT-373898) in healthy subjects
      and in subjects with mild, moderate, and severe hepatic impairment or severe
      renal function impairment (SRFI). After administering a single oral dose of 10 mg
      macitentan the pharmacokinetic parameters including area under the curve from
      zero to infinity (AUCinfinity) were derived from plasma concentration-time
      profiles. Exposure to macitentan and ACT-132577 was lower in hepatically impaired
      versus healthy subjects, with no correlation with the degree of hepatic
      impairment. Exposure to ACT-373898 was lower in subjects with moderate hepatic
      impairment only. Plasma concentration-time profiles for macitentan and ACT-132577
      (active) were similar in healthy subjects and subjects with SRFI. AUCinfinity of
      ACT-373898 (inactive) was 7.3-fold higher in subjects with SRFI versus healthy
      subjects. No safety concerns were raised in either study. Based on these
      observations, pharmacokinetic alterations of macitentan due to hepatic or renal
      function impairment are not considered clinically relevant and no dose adjustment
      is necessary in these patients. 

PMID- 24122796
TI  - Dendritic cells in IBD pathogenesis: an area of therapeutic opportunity?
AB  - Dysfunction of the mucosal immune system plays an important role in inflammatory
      bowel disease (IBD) pathogenesis. Dendritic cells are emerging as central players
      based on both our increasing understanding of how genetic susceptibility impacts
      the mucosal immune system and the key role of dendritic cells in regulating
      response to gut microflora. We discuss areas of therapeutic opportunity in this
      evolving landscape.

PMID- 24122799
TI  - Influenza C virus infection in military recruits--symptoms and clinical
      manifestation.
AB  - Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus
      infections are poorly characterized. Respiratory infections in military recruits
      in eastern Finland were monitored between July 2004 and December 2005 in order to
      study the epidemiology and clinical picture of infections caused by this virus.
      Blood samples were obtained at entry and at the end of the military service, and
      during each episode of respiratory infection to measure antibody responses
      against 10 viral and 2 bacterial pathogens. If possible, sputum samples were
      collected during the acute phase of respiratory infection episodes. Symptoms of
      the episodes were recorded for comparison of the clinical picture caused by
      various infectious agents. Infection with influenza C virus was detected in 38 of
      892 young men during their service. The virus usually caused a mild upper
      respiratory tract infection. Most typical clinical features of influenza C virus
      infection were cough, rhinitis, and hoarseness. A striking difference to
      infections caused by influenza A virus was the lack of fever. Influenza C virus
      is an important cause of a respiratory tract infection in army conscripts.
      Infections with this virus are usually mild but can be complicated in some cases.

PMID- 24122798
TI  - An extensible interface for QM/MM molecular dynamics simulations with AMBER.
AB  - We present an extensible interface between the AMBER molecular dynamics (MD)
      software package and electronic structure software packages for quantum
      mechanical (QM) and mixed QM and classical molecular mechanical (MM) MD
      simulations within both mechanical and electronic embedding schemes. With this
      interface, ab initio wave function theory and density functional theory methods,
      as available in the supported electronic structure software packages, become
      available for QM/MM MD simulations with AMBER. The interface has been written in
      a modular fashion that allows straight forward extensions to support additional
      QM software packages and can easily be ported to other MD software. Data exchange
      between the MD and QM software is implemented by means of files and system calls
      or the message passing interface standard. Based on extensive tests, default
      settings for the supported QM packages are provided such that energy is conserved
      for typical QM/MM MD simulations in the microcanonical ensemble. Results for the
      free energy of binding of calcium ions to aspartate in aqueous solution comparing
      semiempirical and density functional Hamiltonians are shown to demonstrate
      features of this interface.

PMID- 24122800
TI  - Comparison of maternal serum PlGF and sFlt-1 between pregnancies with and without
      fetal hemoglobin Bart's disease.
AB  - OBJECTIVE: The aim of this study was to compare the levels of maternal serum
      placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)
      between pregnancies with fetal hemoglobin (Hb) Bart's disease and unaffected
      pregnancies. METHODS: Ninety-one pregnancies at risk for fetal Hb Bart's disease
      scheduled for cordocentesis at 18-22 weeks were recruited into the study.
      Maternal serum PlGF and sFlt-1 concentrations were measured before cordocentesis.
      Fetal blood samples were collected for thalassemia diagnosis based on fetal Hb
      typing using high-performance liquid chromatography. PlGF, sFlt-1, and sFlt
      1/PlGF ratio were compared between the fetal Hb Bart's group and the non-Hb
      Bart's group (normal Hb typing or alpha-thalassemia-1 carrier). RESULTS: Maternal
      serum concentration of PlGF was significantly higher in women with fetal Hb
      Bart's disease (18 cases) than those with unaffected fetuses (71 cases) (P =
      0.008), whereas the concentration of sFlt-1 was not significantly different (P =
      0.139). However, the sFlt-1/PlGF ratio was significantly lower in women with
      fetal Hb Bart's disease than those with unaffected fetuses (P = 0.001).
      CONCLUSION: Placental growth factor may help differentiate affected from
      unaffected fetuses among pregnancies at risk, though further studies are needed
      to confirm its usefulness. In addition, preeclampsia prediction using these
      markers may be unreliable in pregnancies with placental dysfunction secondary to
      severe fetal anemia.

PMID- 24122802
TI  - HER2 in resected gastric cancer: Is there prognostic value?
AB  - BACKGROUND AND OBJECTIVES: The role of HER2 in patients with early stage/resected
      gastric cancer is controversial. This study investigates the prevalence and
      prognostic value of HER2 in patients undergoing curative intent resection for
      gastric adenocarcinoma. METHODS: HER2 status was evaluated in 111 patients with
      gastric adenocarcinoma treated surgically between 1/00 and 6/11 with tissue
      available for analysis. Immunohistochemistry (IHC) for HER2 was graded by two
      blinded pathologists. IHC was scored as 0+/1+: negative, 2+: equivocal, and 3+:
      positive. Fluorescence in situ hybridization (FISH) for HER2 was performed on
      equivocal (2+) samples, and in cases of pathologist disagreement. RESULTS: HER2
      expression as measured by IHC was negative in 61 (55%), equivocal in 37 (33.3%),
      and positive in 13 (11.7%) cases. FISH was positive in 8 of 37 samples tested,
      for a total of 21 HER2-positive cases (18.9%, 95% CI 11.6-26.2%). Patients with
      HER2-positive tumors were less likely to have signet ring cell features (23.8%
      vs. 53.9%, P = 0.008). HER2 status was not associated with tumor size, location,
      perineural or lymphovascular invasion, margin status, nodal metastasis, or stage
      (P > 0.05). HER2 status was not associated with OS (P = 0.385). CONCLUSIONS: HER2
      amplification/over-expression is present in patients with resected gastric
      adenocarcinoma, but is not associated with the presence of adverse prognostic
      factors. Our results suggest HER2 is not prognostic for patients with resected
      gastric adenocarcinoma.

PMID- 24122801
TI  - The cost implications of prostate cancer screening in the Medicare population.
AB  - BACKGROUND: Recent debate about prostate-specific antigen (PSA)-based testing for
      prostate cancer screening among older men has rarely considered the cost of
      screening. METHODS: A population-based cohort of male Medicare beneficiaries aged
      66 to 99 years, who had never been diagnosed with prostate cancer at the end of
      2006 (n = 94,652), was assembled, and they were followed for 3 years to assess
      the cost of PSA screening and downstream procedures (biopsy, pathologic analysis,
      and hospitalization due to biopsy complications) at both the national and the
      hospital referral region (HRR) level. RESULTS: Approximately 51.2% of men
      received PSA screening tests during the 3-year period, with 2.9% undergoing
      biopsy. The annual expenditures on prostate cancer screening by the national fee
      for-service Medicare program were $447 million in 2009 US dollars. The mean
      annual screening cost at the HRR level ranged from $17 to $62 per beneficiary.
      Downstream biopsy-related procedures accounted for 72% of the overall screening
      costs and varied significantly across regions. Compared with men residing in HRRs
      that were in the lowest quartile for screening expenditures, men living in the
      highest HRR quartile were significantly more likely to be diagnosed with prostate
      cancer of any stage (incidence rate ratio [IRR] = 1.20, 95% confidence interval
      [CI] = 1.07-1.35) and localized cancer (IRR = 1.30, 95% CI = 1.15-1.47). The IRR
      for regional/metastasized cancer was also elevated, although not statistically
      significant (IRR = 1.31, 95% CI = 0.81-2.11). CONCLUSIONS: Medicare prostate
      cancer screening-related expenditures are substantial, vary considerably across
      regions, and are positively associated with rates of cancer diagnosis.

PMID- 24122803
TI  - Comparison of toxicity of different nanorod-type TiO2 polymorphs in vivo and in
      vitro.
AB  - It is predicted that the toxicity of nanoparticles may be different depending on
      the properties of the nanoparticles and biological system being tested. However,
      the factors that influence the toxicity of nanoparticles have not been adequately
      investigated. In this study, we characterized two types of TiO2 nanorods, anatase
      (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO
      and BTO differed from each other most notably in their surface areas. Treatment
      with the two TiO2 nanorods (10 ug ml(-1) ) produced similar effects on the cell
      cycle in eight cell lines which are derived from potential target organs of
      nanoparticles, with the BTO eliciting stronger responses than ATO in all cell
      lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice
      were exposed to two TiO2 nanorods (1 mg kg(-1) ), BTO induced clearer
      histopathological lesions and triggered a more robust secretion of inflammatory
      cytokines than ATO. Furthermore, we compared the cellular response of both TiO2
      nanorods using BEAS-2B cells, the human bronchial epithelial cell line. Both
      nanorods induced cell death by increasing the formation of autophagosome-like
      vacuoles. The mitochondrial calcium concentration decreased by exposure of both
      types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a
      clear difference between the two nanorods. Thus, we conclude that the surface
      area acts as an important factor which depends on toxicity of nanorod type-TiO2
      nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the
      type of cells tested, and that the assembly of autophagosome-like vacuoles is a
      critical part of the cellular response to nanoparticle exposure.

PMID- 24122804
TI  - Changes of DNA quality and meat physicochemical properties in bovine
      supraspinatus muscle during microwave heating.
AB  - BACKGROUND: The responses of foods to microwave exposure are usually evaluated
      only in terms of physicochemical properties, thus undervaluing the importance of
      DNA in an authentication process by methods based on polymerase chain reaction
      (PCR). In this study, the time effect of microwave heating on some meat
      physicochemical properties and DNA quality has been investigated. RESULTS:
      Cooking loss, instrumental colour, pH and other physicochemical parameters varied
      significantly during microwave cooking, reaching the lowest/highest values after
      2.5 min of cooking. The exposure of meat to microwaves was found to affect
      characteristically the quality of extracted DNA (i.e. yield, purity and
      degradation). PCR products of both mitochondrial and nuclear regions were
      successfully observed in all samples. However, the band for large fragments
      became progressively fainter as treatment time increased. CONCLUSIONS: Microwave
      heating caused physicochemical changes in bovine supraspinatus muscle and
      influenced characteristically the yield and integrity of the extracted DNA,
      indicating that an accurate DNA quantification and a rational choice of the genes
      (i.e. mtDNA versus nDNA, fragment size, etc.) to be amplified are fundamental in
      an authentication process by PCR-based methods.

PMID- 24122806
TI  - Reply: To PMID 22334511.

PMID- 24122805
TI  - Determination of a novel diacylglycerol acyltransferase 1 inhibitor, 2-[4-(4-{5
      [2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido]-1H-benzo[d]imidazol-2-yl}
      phenyl) cyclohexyl] acetic acid (KR-69232) in rat plasma using liquid
      chromatography-tandem mass spectrometry and its application to a pharmacokinetic
      study.
AB  - A liquid chromatography-tandem mass spectrometry method was developed and
      validated for the quantification of KR-69232, a diacyltransferase 1 inhibitor, in
      rat plasma. KR-69232 in the concentration range of 0.004-4 ug/mL was linear. The
      intra-and inter-day precision and accuracy were acceptable (<20%). KR-69232 was
      stable under various storage and handling conditions. The method was applied
      successfully in a pharmacokinetic study of KR-69232 in rats.

PMID- 24122807
TI  - Angiogenin stimulates ribosomal RNA transcription by epigenetic activation of the
      ribosomal DNA promoter.
AB  - Angiogenin (ANG) undergoes nuclear translocation and promotes ribosomal RNA
      (rRNA) transcription thereby enhancing cell growth and proliferation. However,
      the mode of action of ANG in stimulating rRNA transcription is unclear. Here, we
      show that ANG enhances the formation of RNA polymerase I (Pol I) pre-initiation
      complex at the ribosomal DNA (rDNA) promoter. ANG binds at the upstream control
      element (UCE) of the promoter and enhances promoter occupancy of RNA Pol I as
      well as the selectivity factor SL1 components TAFI 48 and TAFI 110. We also show
      that ANG increases the number of actively transcribing rDNA by epigenetic
      activation through promoter methylation and histone modification. ANG binds to
      histone H3, inhibits H3K9 methylation, and activates H3K4 methylation as well as
      H4 acetylation at the rDNA promoter. These data suggest that one of the
      mechanisms by which ANG stimulates rRNA transcription is through an epigenetic
      activation of rDNA promoter.

PMID- 24122808
TI  - Shifts in EMG spectral power during fatiguing dynamic contractions.
AB  - INTRODUCTION: We examined the etiology of the electromyographic (EMG) spectral
      shift during dynamic fatigue. METHODS: Nineteen subjects (mean +/- SD age = 22.4
      +/- 1.6 years) performed 50 consecutive maximal concentric isokinetic
      contractions of dominant leg extensors. Surface EMG signals were detected from
      the vastus lateralis, rectus femoris, and vastus medialis during each
      contraction, processed with a wavelet analysis, and the resulting spectra were
      decomposed with a nonparametric spectral decomposition procedure. RESULTS: The
      results indicated that the decreases in EMG frequency during the 50 contractions
      were generally due to reductions in high-frequency power and increases in low
      frequency power. In addition, the spectral shifts were most pronounced for the
      rectus femoris, followed by the vastus lateralis, and then the vastus medialis.
      CONCLUSIONS: The spectral decomposition procedure is much more sensitive for
      tracking dynamic fatigue than is EMG mean frequency or median frequency.

PMID- 24122809
TI  - Organ preservation surgery for low- and intermediate-grade laryngeal
      chondrosarcomas: analysis of 16 cases.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate that endoscopic resection (ER), open
      partial laryngectomies, and cricotracheal resection and anastomosis (CTRA)
      achieve a good balance between oncologic radicality and organ preservation for
      laryngeal low-grade chondrosarcoma (LCS) and intermediate-grade chondrosarcoma
      (ICS). STUDY DESIGN: Retrospective series in an academic institution. METHODS:
      Between 2001 and 2013, we treated 13 cricoid, two thyroid, and one arytenoid LCS
      and ICS. Two cricoid and the only arytenoid LCS were managed by ER. Two thyroid
      ala LCS were submitted to laminectomy. Five ICS and six LCS of the cricoid
      received CTRA. RESULTS: Nine patients only required tracheotomy, removed after a
      maximum of 14 days. Three patients required a nasogastric feeding tube, removed
      after a maximum of 8 days. Immediate complications included one bleeding, one
      cervical emphysema, and one partial anastomotic dehiscence. The only late
      complication was anastomotic stenosis that was resolved by laser resection. All
      patients regained regular oral feeding and a voice ranging from normal to
      moderate dysphonia. At the last follow-up, two patients died of unrelated causes,
      seven are alive with asymptomatic and radiologically stable residual disease, and
      seven are alive without evidence of persistent disease. One patient received
      total laryngectomy 11 years after CTRA for recurrent symptomatic disease.
      CONCLUSIONS: Organ preservation surgery for laryngeal LCS and ICS represents a
      treatment option with low morbidity, good quality of life, and fair possibility
      to obtain oncologic radicality. LEVEL OF EVIDENCE: 4.

PMID- 24122811
TI  - Highly asymmetric electrolytes in the primitive model: hypernetted chain solution
      in arbitrary spatial dimensions.
AB  - The pair-correlation functions for fluid ionic mixtures in arbitrary spatial
      dimensions are computed in hypernetted chain (HNC) approximation. In the
      primitive model (PM), all ions are approximated as nonoverlapping hyperspheres
      with Coulomb interactions. Our spectral HNC solver is based on a Fourier-Bessel
      transform introduced by Talman (J. Comput. Phys. 1978, 29, 35), with
      logarithmically spaced computational grids. Numeric efficiency for arbitrary
      spatial dimensions is a commonly exploited virtue of this transform method. Here,
      we highlight another advantage of logarithmic grids, consisting in efficient
      sampling of pair-correlation functions for highly asymmetric ionic mixtures. For
      three-dimensional fluids, ion size and charge-ratios larger than 1000 can be
      treated, corresponding to hitherto computationally not accessed micrometer-sized
      colloidal spheres in 1-1 electrolyte. Effective colloidal charge numbers are
      extracted from our PM results. For moderately large ion size and charge
      asymmetries, we present molecular dynamics simulation results that agree well
      with the approximate HNC pair correlations.

PMID- 24122810
TI  - Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique
      molecular subtype of cholangiocarcinoma.
AB  - Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in
      which the molecular mechanisms underlying tumor development remain poorly
      understood. Identification of a novel driver oncogene and applying it to targeted
      therapies for molecularly defined cancers might lead to improvements in the
      outcome of patients. We performed massively parallel whole transcriptome
      sequencing in eight specimens from cholangiocarcinoma patients without
      KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1
      and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR)
      screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma
      (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in
      colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric
      cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF
      mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and
      conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous
      transplanted cells in immune-compromised mice. This transforming ability was
      attributable to its kinase activity. Treatment with the fibroblast growth factor
      receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed
      transformation. CONCLUSION: FGFR2 fusions occur in 13.6% of intrahepatic
      cholangiocarcinoma. The expression pattern of these fusions in association with
      sensitivity to FGFR inhibitors warrant a new molecular classification of
      cholangiocarcinoma and suggest a new therapeutic approach to the disease.

PMID- 24122812
TI  - Expression of IL-33 and its receptor ST2 in chronic rhinosinusitis with nasal
      polyps.
AB  - OBJECTIVES/HYPOTHESIS: Interleukin (IL)-33 is a novel member of the IL-1 cytokine
      family and a ligand for the orphan IL-1 family receptor ST2. IL-33 induces T
      helper 2-type inflammatory responses and is considered to play a crucial role in
      allergic inflammatory reactions such as asthma and atopic dermatitis. However,
      the role of IL-33 and its receptor ST2 in chronic rhinosinusitis remains unclear.
      STUDY DESIGN: In vitro study. METHODS: The expression patterns of IL-33 and ST2
      at both mRNA and protein levels in nasal polyps from eosinophilic chronic
      rhinosinusitis (ECRS) patients (n = 10) and non-ECRS patients (n = 13), as well
      as in seemingly normal mucosa of the uncinate processes in patients without
      sinusitis (control; n = 5), were compared using immunohistochemical staining,
      enzyme-linked immunosorbent assay, and real-time polymerase chain reactions.
      RESULTS: ST2-positive cells in the inflammatory cells in the subepithelial layer
      were significantly higher in the ECRS group than other groups. The expression of
      ST2 mRNA in polyps of the ECRS group was significantly increased compared with
      controls. Many ST2-positive eosinophils were observed in the mucosa of ECRS but
      not in the mucosa of non-ECRS patients. The expression level of IL-33 mRNA was
      not significantly different among the three groups. CONCLUSIONS: The current
      study suggests that IL-33 and its receptor ST2 may play important roles in the
      pathogenesis of chronic rhinosinusitis, especially in ECRS, through the increased
      expression of ST2 in eosinophils. LEVEL OF EVIDENCE: N/A.

PMID- 24122813
TI  - Epigenetic dysregulation of leukaemic HOX code in MLL-rearranged leukaemia mouse
      model.
AB  - HOX genes are frequently dysregulated in human leukaemia with the gene
      rearrangement between mixed lineage leukaemia (MLL) and partner genes. The
      resultant MLL fusion proteins are known to mediate leukaemia through disruption
      of the normal epigenetic regulation at the target gene loci. To elucidate the
      pathogenic role of MLL fusion proteins in HOX dysregulation in leukaemia, we
      generated a novel haematopoietic lineage-specific Mll-Een knock-in mouse model
      using a Cre-mediated inversion strategy. The Mll(Een) (/+) invertor mice
      developed acute myeloid leukaemia, with organomegaly of the spleen, liver and
      mesenteric lymph nodes caused by infiltration of blast cells. Using Mll-Een
      expressing leukaemic cell lines derived from bone marrow of Mll(Een) (/+) mutant
      mice, we showed that induction of Hox genes in leukaemic cells was associated
      with hypomethylated promoter regions and an aberrant active chromatin state at
      the Hox loci. Knock-down of Prmt1 was insufficient to reverse the active
      chromatin status and the hypomethylated Hox loci, suggesting that Prmt1-mediated
      histone arginine methylation was only partially involved in the maintenance of
      Hox expression in leukaemic cells. Furthermore, in vivo analysis of bone marrow
      cells of Mll(Een) (/+) mice revealed a Hox expression profile similar to that of
      wild-type haematopoietic stem cells. The leukaemic Hox profile was highly
      correlated with aberrant hypomethylation of Hox promoters in the mutant mice,
      which highlights the importance of DNA methylation in leukaemogenic mechanisms
      induced by MLL fusion proteins. Our results point to the involvement of dynamic
      epigenetic regulations in the maintenance of the stem cell-like HOX code that
      initiates leukaemic stem cells in MLL-rearranged leukaemia. This provides
      insights for the development of alternative strategies for leukaemia treatment.

PMID- 24122814
TI  - A multiple ascending dose study of CSL112, an infused formulation of ApoA-I.
AB  - CSL112 is apoA-I purified from human plasma and reconstituted with
      phosphatidylcholine (PC) to form high-density lipoprotein (HDL)-particles
      suitable for infusion. CSL112 is in development for the potential treatment of
      acute coronary syndromes (ACS) by optimizing cholesterol efflux. This study
      assesses the pharmacokinetics (PK), safety and tolerability of CSL112. Repeat
      doses of CSL112 or placebo were administered intravenously once- (3.4 g or 6.8 g)
      or twice-weekly (3.4 g) to healthy subjects in a placebo-controlled, randomized
      (3 CSL112: 1 placebo), ascending-dose study (NCT01281774). Twenty-seven subjects
      received CSL112 and nine received placebo. Study endpoints included plasma apoA-I
      and PC concentrations and specific PK parameters. CSL112 infusions immediately
      produced robust increases in apoA-I concentration in a dose-proportional manner,
      reaching levels higher than observed with currently available or investigational
      HDL products. After infusion of CSL112, apoA-I levels remained above baseline for
      approximately 3 days. Multiple infusions of CSL112 were safe and well tolerated
      with no evidence of major organ toxicity or immunogenicity. CSL112 may provide a
      novel option to rapidly transport cholesterol from atherosclerotic plaque to the
      liver and reduce early recurrent events following ACS. The data presented here
      support continued clinical development of CSL112 in patient populations. 

PMID- 24122815
TI  - Psychosocial factors affecting uptake of prenatal genetic testing: a pilot study.
AB  - OBJECTIVE: This study aims to explore the psychosocial factors which influenced
      the undergoing of prenatal genetic testing (PGT) in a sample of pregnant women.
      METHOD: An online questionnaire was emailed to a convenient sample of 105
      pregnant women, recruited from among those attending two antenatal education
      programmes and via snowball sampling. RESULTS: A minority of respondents
      underwent chorionic villous sampling and amniocentesis (12 and 11, respectively).
      Advanced maternal age was related to undertaking PGT. The path analysis model
      (chi(2) (16, N = 97) = 19.01, ns; TLI = 0.95; RMSEA = 0.04; WRMR = 0.64)
      confirmed that three dimensions, namely having a more supporting attitude towards
      PGT (beta = 0.54, p < 0.001), perceiving PGT as reliable (beta = 0.29, p < 0.05)
      and the request for more scientific information (beta = 0.22, p < 0.01), related
      to test uptaking. CONCLUSION: Empirical researches investigating pregnant women's
      beliefs and attitudes relating to actual test uptake could help genetic
      counsellors and policy makers to better understand their client's profile in
      relation to the determining factors affecting the undertaking of PGT.

PMID- 24122816
TI  - Cultural competency in health care and its implications for pharmacy part 3A:
      emphasis on pharmacy education, curriculums, and future directions.
AB  - Culture influences patients' beliefs and behaviors toward health and illness. As
      the U.S. population becomes more diverse, a critical need exists for pharmacy
      education to incorporate patient-centered culturally sensitive health care
      knowledge and skills into the curriculum. Nursing was the first profession to
      incorporate this type of learning and training into its curriculums, followed by
      medicine. Pharmacy has also made great progress to revise curriculums, but
      inconsistency exists in depth, breadth, and methods across pharmacy colleges.
      This article addresses important aspects of pharmacy education such as curriculum
      development, incorporation of educational innovations and techniques into the
      teaching of patient-centered culturally sensitive health care across the
      curriculum from didactic to experiential learning, assessment tools, and global
      education. A preliminary model curriculum with objectives and examples of
      teaching methods is proposed. Future directions in pharmacy education, teaching
      and learning scholarship, postgraduate education, licensure, and continuing
      education are also presented. 

PMID- 24122817
TI  - Management of recurrent rectal cancer: practical insights in planning and
      surgical intervention.
AB  - Over the last two decades the oncologic treatment results for primary rectal
      cancer have improved due to refinements in neoadjuvant chemotherapy, radiation,
      and surgery. Nevertheless, there is still a 10% rate of local recurrence,
      threatening the survival and quality of life of affected patients. Due to
      variability of anatomy and clinical presentation, detection, staging, and
      clinical management are complex. Without treatment, patients will suffer from
      progressive local symptoms-pain, obstruction, hemorrhage, sepsis-and rarely
      survive beyond five years. The overall goals of surgical treatment-complete tumor
      resection, preservation of function, and avoidance of complications-are identical
      to those of surgery for primary rectal cancer, but are unfortunately much more
      difficult to achieve in the setting of recurrence. Tumor resection is highly
      challenging, as the surgical field has generally been anatomically disrupted and
      irradiated, and the tumors are typically adherent or invasive into organs in the
      middle and low pelvis. Standard total mesorectal excision (TME) resections are
      rarely sufficient, and therefore techniques to achieve extended multivisceral
      resections are required. While aggressive resections offer the best opportunity
      for local control, palliation, and cure, they also carry a high risk of
      complications and long-term morbidity. The aim of this review is to provide an
      updated look at surgical resection for recurrent rectal cancer, its indications,
      preoperative considerations, operative technique, intraoperative radiotherapy
      (IORT) and long-term outcomes and sequelae.

PMID- 24122818
TI  - HPLC-Q-TOF-MS/MS for analysis of major chemical constituents of Yinchen-Zhizi
      herb pair extract.
AB  - The Yinchen-Zhizi herb pair (YZHP) consists of Herba Artemisiae Scopariae
      (Yinchen in Chinese) and Fructus Gardeniae (Zhizi in Chinese), and is mainly used
      to treat icteric hepatitis, itching skin and eczema. However, the bioactive
      constituents responsible for the pharmacological effects of YZHP are still
      unclear to date. In this work, a rapid and sensitive method was established to
      comprehensively study the constituents in YZHP extract by HPLC-Q-TOF MS/MS. The
      analysis was performed on an HPLC system equipped with an Agilent poroshell 120
      EC-C18 column (100 * 2.1 mm, 2.7 mm) working in a gradient elution program
      coupled to quadrupole-time-of-flight mass spectrometry operating in the negative
      ion mode. As a result, a total of 46 compounds including 17 from Herba Artemisiae
      Scopariae and 36 from Fructus Gardeniae were detected and tentatively identified
      in YZHP extract by comparing the retention time and mass spectrometry and
      retrieving the reference literature. More importantly, a series of constituents,
      such as many iridoid glycosides, were reported for the first time in this
      formula. The HPLC-Q-TOF MS/MS method was developed and utilized successfully to
      identify the major constituents in YZHP extract and would be helpful for further
      metabolism and pharmacology research on YZHP.

PMID- 24122819
TI  - Astrocyte plasticity: implications for synaptic and neuronal activity.
AB  - Astrocytes are increasingly implicated in a range of functions in the brain, many
      of which were previously ascribed to neurons. Much of the prevailing interest
      centers on the role of astrocytes in the modulation of synaptic transmission and
      their involvement in the induction of forms of plasticity such as long-term
      potentiation and long-term depression. However, there is also an increasing
      realization that astrocytes themselves can undergo plasticity. This plasticity
      may be manifest as changes in protein expression which may modify calcium
      activity within the cells, changes in morphology that affect the environment of
      the synapse and the extracellular space, or changes in gap junction astrocyte
      coupling that modify the transfer of ions and metabolites through astrocyte
      networks. Plasticity in the way that astrocytes release gliotransmitters can also
      have direct effects on synaptic activity and neuronal excitability. Astrocyte
      plasticity can potentially have profound effects on neuronal network activity and
      be recruited in pathological conditions. An emerging principle of astrocyte
      plasticity is that it is often induced by neuronal activity, reinforcing our
      emerging understanding of the working brain as a constant interaction between
      neurons and glial cells. 

PMID- 24122820
TI  - Molecular architecture of myelinated nerve fibers: leaky paranodal junctions and
      paranodal dysmyelination.
AB  - Myelinated nerve fibers have evolved to optimize signal propagation. Each myelin
      segment is attached to the axon by the unique paranodal axoglial junction (PNJ),
      a highly complex structure that serves to define axonal ion channel domains and
      to direct nodal action currents through adjacent nodes. Surprisingly, this
      junction does not entirely seal the paranodal myelin sheath to the axon and thus
      does not entirely isolate the perinodal space from the internodal periaxonal
      space. Rather the paranode is penetrated by extracellular pathways between the
      myelin sheath and the axolemma for movement of molecules and the flow of current
      to and from the internodal axon. This review summarizes past and current studies
      demonstrating these pathways and considers what functional roles they subserve.
      In addition, modern genetic engineering methods permit modification of individual
      PNJ constituents, which provides an opportunity to define their specific
      functions. One component in particular, the transverse bands, plays a key role in
      maintaining the structure and function of the PNJ. Loss of transverse bands
      results not in frank demyelination but rather in subtle dysmyelination, which
      causes significant functional impairment. The consequences of such subtle defects
      in the PNJ are considered along with the relevance of these studies to human
      diseases of myelin. 

PMID- 24122821
TI  - Glial biology in learning and cognition.
AB  - Neurons are exquisitely specialized for rapid electrical transmission of signals,
      but some properties of glial cells, which do not communicate with electrical
      impulses, are well suited for participating in complex cognitive functions
      requiring broad spatial integration and long-term temporal regulation.
      Astrocytes, microglia, and oligodendrocytes all have biological properties that
      could influence learning and cognition. Myelination by oligodendrocytes increases
      conduction velocity, affecting spike timing and oscillations in neuronal
      activity. Astrocytes can modulate synaptic transmission and may couple multiple
      neurons and synapses into functional assemblies. Microglia can remove synapses in
      an activity-dependent manner altering neural networks. Incorporating glia into a
      bicellular mechanism of nervous system function may help answer long-standing
      questions concerning the cellular mechanisms of learning and cognition. 

PMID- 24122822
TI  - An analytic method for the placebo-based pattern-mixture model.
AB  - Pattern-mixture models provide a general and flexible framework for sensitivity
      analyses of nonignorable missing data. The placebo-based pattern-mixture model
      (Little and Yau, Biometrics 1996; 52:1324-1333) treats missing data in a
      transparent and clinically interpretable manner and has been used as sensitivity
      analysis for monotone missing data in longitudinal studies. The standard multiple
      imputation approach (Rubin, Multiple Imputation for Nonresponse in Surveys, 1987)
      is often used to implement the placebo-based pattern-mixture model. We show that
      Rubin's variance estimate of the multiple imputation estimator of treatment
      effect can be overly conservative in this setting. As an alternative to multiple
      imputation, we derive an analytic expression of the treatment effect for the
      placebo-based pattern-mixture model and propose a posterior simulation or delta
      method for the inference about the treatment effect. Simulation studies
      demonstrate that the proposed methods provide consistent variance estimates and
      outperform the imputation methods in terms of power for the placebo-based pattern
      mixture model. We illustrate the methods using data from a clinical study of
      major depressive disorders.

PMID- 24122823
TI  - Increased prevalence of the alpha-1-antitrypsin (A1AT) deficiency-related S gene
      in patients infected with human immunodeficiency virus type 1.
AB  - Large variation exists in susceptibility to infection with Human Immunodeficiency
      Virus Type 1 (HIV), and disease progression. These observations demonstrate a
      role for antiretroviral host factors. Several reports describe alpha1-antitrypsin
      (A1AT), the most abundant circulating serine protease inhibitor, as a potent
      suppressor of HIV infection and replication. We identified the normal (M) and
      most common deficiency-associated (S and Z) isoforms of the A1AT gene in patients
      infected with HIV from four multicenter cohorts. The level of disease progression
      in the patients was characterized and the patients were grouped into as elite
      controllers (EC), long-term non-progressors (LTNP), or progressors (Prog). No
      significant difference in the distribution of A1AT alleles was observed in the
      EC, LTNP, or Prog groups. However, significantly increased prevalence of the A1AT
      deficiency-associated S allele was observed in HIV-infected patients compared to
      the prevalence of S A1AT in the general population. These results suggest that
      deficiency in A1AT may be a risk factor for acquisition of HIV infection, but
      physiological A1AT concentrations do not affect disease progression after
      infection occurs.

PMID- 24122824
TI  - Recurrent hepatic epithelioid hemangioendothelioma after orthotopic liver
      transplantation.

PMID- 24122825
TI  - Which is the best grape seed additive for frankfurters: extract, oil or flour?
AB  - BACKGROUND: Grape seed products (winery by-products) are valuable vegetable
      sources to enhance the quality of meat products. In this study, 21 treatments of
      frankfurters, in three different groups, including 0%, 0.01%, 0.03%, 0.05%, 0.1%,
      0.3% and 0.5% grape seed extract (GSE), 0%, 1%, 2%, 4%, 6%, 8% and 10% grape seed
      oil (GSO), and 0%, 0.5%, 1%, 2%, 3%, 4% and 5% grape seed flour (GSF) were
      produced in order to compare the differences among them during refrigerated
      storage for 90 days. RESULTS: Increasing the level of GSO made the frankfurters
      lighter in color (P < 0.05). Lipid oxidation of all the 21 frankfurters were
      under the limit of deterioration (2.0 mg malonaldehite kg-1 treatment) during 90
      days' storage. However, increasing the amount of additives (GSE, GSO and GSF) led
      to a decrease in overall acceptability for each group. According to the general
      comparison of the three frankfurter groups in terms of lipid oxidation, TBARS
      (thiobarbituric acid reactive substances) values of the frankfurters including
      GSE and GSF were found to be similar, but the frankfurters containing GSO
      exhibited the highest lipid oxidation (P < 0.05). While the products including
      GSE were the most acceptable group in terms of overall acceptability, the group
      produced with GSF received the lowest points (P < 0.05). CONCLUSION: Although the
      three grape seed products have partially undesirable effects on the sensory
      characteristics of the frankfurters, all these additives showed different
      positive influences in the production of frankfurters. The results showed that
      the group of frankfurters including GSE was the best of three different groups of
      products due to the lipid oxidation and overall acceptability results.

PMID- 24122826
TI  - Analysis of comorbidities and objective parameters in refractory chronic
      rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to construct the clinical
      profile of patients with chronic rhinosinusitis (CRS) with/without polyposis
      undergoing revision sinus surgery and to evaluate the relationship of polyposis,
      asthma, acetylsalicylic acid (aspirin) (ASA) sensitivity, inhalant allergies, and
      previous sinus surgery on disease severity as measured by objective parameters.
      STUDY DESIGN: Cross-sectional study. METHODS: Two-hundred twenty-five patients
      were accrued at a tertiary care academic center. Categorical factors recorded
      included presence of polyps, asthma, inhalant allergy, and ASA sensitivity.
      Continuous variables assessed included mean number of previous sinus surgeries,
      Lund-Kennedy endoscopy score, Lund-Mackay computed tomography (CT) score,
      absolute eosinophil count (AEC), and total immunoglobulin E (tIgE) level.
      Statistical analysis was performed to analyze the impact of polyposis, asthma,
      inhalant allergy, and ASA sensitivity on objective parameters. The mean number of
      previous surgeries was also correlated with objective parameters. RESULTS: The
      mean age was 50.1 years with a male:female ratio of 1.1:1. The overall prevalence
      of polyposis, asthma, inhalant allergy, and ASA sensitivity was 56.4%, 48.4%,
      38.7%, and 16.0%, respectively. The mean endoscopy and CT scores were 9.0 (+/-
      4.0) and 11.4 (+/- 5.8), respectively. The mean AEC and tIgE were 0.4 k/MUL (+/-
      0.4) and 161.4 IU/mL (+/- 251.4). The mean number of previous endoscopic sinus
      surgeries was 1.8. Patients with CRS with polyposis had a statistically
      significant increase in presence of asthma (odds ratio [OR]: 7.5, P < .0001),
      inhalant allergy (OR: 3.6, P < .0001), and ASA sensitivity (OR: 78.6, P < .0001).
      Patients with polyposis had a statistically significant increase in endoscopy
      score (P < .0001), CT score (P < .0001), AEC (P < .0001), and tIgE (P = .0002).
      Patients with asthma had a statistically significant increase in endoscopy (P <
      .0001) and CT scores (P < .0001), AEC (P < .0001), and tIgE (P = .0002). Patients
      with inhalant allergy had a statistically significant increase in endoscopy (P =
      .0069), CT scores (P = .0017), and tIgE (P = .0084) but not AEC (P = .1492).
      Patients with ASA sensitivity had a statistically significant increase in
      endoscopy score (P < .0001), CT score (P < .0001), and AEC (P = .003) but not
      tIgE level (P = .186). The number of previous surgeries had a statistically
      significant correlation with endoscopy (P = .006) and CT scores (P = .03) but not
      AEC (P = .48) or tIgE (P = .66). CONCLUSIONS: The current analysis constructed
      the clinical profile of the recalcitrant CRS patient undergoing revision sinus
      surgery. In general, this patient group has a high prevalence of polyposis,
      asthma, inhalant allergy, ASA sensitivity, and elevated disease burden as
      measured by objective measures. The polyp phenotype signifies statistically
      higher prevalence of associated comorbidities and greater objective disease
      severity. The presence of asthma, inhalant allergy, and ASA sensitivity also
      predicts statistically higher disease burden. The endoscopy and CT scores
      statistically correlate with the number of previous surgeries. LEVEL OF EVIDENCE:
      4 Laryngoscope, 123:E1-E11, 2013.

PMID- 24122827
TI  - Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery
      in exosomes from mouse or human hepatic stellate cells.
AB  - Connective tissue growth factor (CCN2) drives fibrogenesis in hepatic stellate
      cells (HSC). Here we show that CCN2 up-regulation in fibrotic or steatotic
      livers, or in culture-activated or ethanol-treated primary mouse HSC, is
      associated with a reciprocal down-regulation of microRNA-214 (miR-214). By using
      protector or reporter assays to investigate the 3'-untranslated region (UTR) of
      CCN2 mRNA, we found that induction of CCN2 expression in HSC by fibrosis-inducing
      stimuli was due to reduced expression of miR-214, which otherwise inhibited CCN2
      expression by directly binding to the CCN2 3'-UTR. Additionally, miR-214 was
      present in HSC exosomes, which were bi-membrane vesicles, 50-150 nm in diameter,
      negatively charged (-26 mV), and positive for CD9. MiR-214 levels in exosomes but
      not in cell lysates were reduced by pretreatment of the cells with the exosome
      inhibitor, GW4869. Coculture of either quiescent HSC or miR-214-transfected
      activated HSC with CCN2 3'-UTR luciferase reporter-transfected recipient HSC
      resulted in miR-214- and exosome-dependent regulation of a wild-type CCN2 3'-UTR
      reporter but not of a mutant CCN2 3'-UTR reporter lacking the miR-214 binding
      site. Exosomes from HSC were a conduit for uptake of miR-214 by primary mouse
      hepatocytes. Down-regulation of CCN2 expression by miR-214 also occurred in human
      LX-2 HSC, consistent with a conserved miR-214 binding site in the human CCN2 3'
      UTR. MiR-214 in LX-2 cells was shuttled by way of exosomes to recipient LX-2
      cells or human HepG2 hepatocytes, resulting in suppression of CCN2 3'-UTR
      activity or expression of CCN2 downstream targets, including alpha smooth muscle
      actin or collagen. Experimental fibrosis in mice was associated with reduced
      circulating miR-214 levels. CONCLUSION: Exosomal transfer of miR-214 is a
      paradigm for the regulation of CCN2-dependent fibrogenesis and identifies
      fibrotic pathways as targets of intercellular regulation by exosomal miRs.

PMID- 24122828
TI  - Nitrogen limitation adaptation, a target of microRNA827, mediates degradation of
      plasma membrane-localized phosphate transporters to maintain phosphate
      homeostasis in Arabidopsis.
AB  - Members of the Arabidopsis thaliana phosphate transporter1 (PHT1) family are key
      players in acquisition of Pi from the rhizosphere, and their regulation is
      indispensable for the maintenance of cellular Pi homeostasis. Here, we reveal
      posttranslational regulation of Pi transport through modulation of degradation of
      PHT1 proteins by the RING-type ubiquitin E3 ligase, nitrogen limitation
      adaptation (NLA). Loss of function of NLA caused high Pi accumulation resulting
      from increases in the levels of several PHT1s at the protein rather than the
      transcript level. Evidence of decreased endocytosis and ubiquitination of PHT1s
      in nla mutants and interaction between NLA and PHT1s in the plasma membranes
      suggests that NLA directs the ubiquitination of plasma membrane-localized PHT1s,
      which triggers clathrin-dependent endocytosis followed by endosomal sorting to
      vacuoles. Furthermore, different subcellular localization of NLA and phosphate2
      (pho2; a ubiquitin E2 conjugase) and the synergistic effect of the accumulation
      of PHT1s and Pi in nla pho2 mutants suggest that they function independently but
      cooperatively to regulate PHT1 protein amounts. Intriguingly, NLA and PHO2 are
      the targets of two Pi starvation-induced microRNAs, miR827 and miR399,
      respectively. Therefore, our findings uncover modulation of Pi transport activity
      in response to Pi availability through the integration of a microRNA-mediated
      posttranscriptional pathway and a ubiquitin-mediated posttranslational regulatory
      pathway.

PMID- 24122829
TI  - Identification of downstream components of ubiquitin-conjugating enzyme
      PHOSPHATE2 by quantitative membrane proteomics in Arabidopsis roots.
AB  - MicroRNA399-mediated regulation of the ubiquitin-conjugating enzyme
      UBC24/phosphate2 (PHO2) is crucial for Pi acquisition and translocation in
      plants. Because of a potential role for PHO2 in protein degradation and its
      association with membranes, an iTRAQ (for isobaric tags for relative and absolute
      quantitation)- based quantitative membrane proteomic method was employed to
      search for components downstream of PHO2. A total of 7491 proteins were
      identified from Arabidopsis thaliana roots by mass spectrometry, 35.2% of which
      were predicted to contain at least one transmembrane helix. Among the
      quantifiable proteins, five were significantly differentially expressed between
      the wild type and pho2 mutant under two growth conditions. Using immunoblot
      analysis, we validated the upregulation of several members in phosphate
      transporter1 (PHT1) family and phosphate transporter traffic facilitator1 (PHF1)
      in pho2 and demonstrated that PHO2 mediates the degradation of PHT1 proteins.
      Genetic evidence that loss of PHF1 or PHT1;1 alleviated Pi toxicity in pho2
      further suggests that they play roles as downstream components of PHO2. Moreover,
      we showed that PHO2 interacts with PHT1s in the postendoplasmic reticulum
      compartments and mediates the ubiquitination of endomembrane-localized PHT1;1.
      This study not only uncovers a mechanism by which PHO2 modulates Pi acquisition
      by regulating the abundance of PHT1s in the secretory pathway destined for plasma
      membranes, but also provides a database of the membrane proteome that will be
      widely applicable in root biology research.

PMID- 24122830
TI  - Replication protein A2c coupled with replication protein A1c regulates crossover
      formation during meiosis in rice.
AB  - Replication protein A (RPA) is a conserved heterotrimeric protein complex
      comprising RPA1, RPA2, and RPA3 subunits involved in multiple DNA metabolism
      pathways attributable to its single-stranded DNA binding property. Unlike other
      species possessing a single RPA2 gene, rice (Oryza sativa) possesses three RPA2
      paralogs, but their functions remain unclear. In this study, we identified RPA2c,
      a rice gene preferentially expressed during meiosis. A T-DNA insertional mutant
      (rpa2c) exhibited reduced bivalent formation, leading to chromosome
      nondisjunction. In rpa2c, chiasma frequency is reduced by ~78% compared with the
      wild type and is accompanied by loss of the obligate chiasma. The residual ~22%
      chiasmata fit a Poisson distribution, suggesting loss of crossover control. RPA2c
      colocalized with the meiotic cohesion subunit REC8 and the axis-associated
      protein PAIR2. Localization of REC8 was necessary for loading of RPA2c to the
      chromosomes. In addition, RPA2c partially colocalized with MER3 during late
      leptotene, thus indicating that RPA2c is required for class I crossover formation
      at a late stage of homologous recombination. Furthermore, we identified RPA1c, an
      RPA1 subunit with nearly overlapping distribution to RPA2c, required for ~79% of
      chiasmata formation. Our results demonstrate that an RPA complex comprising RPA2c
      and RPA1c is required to promote meiotic crossovers in rice.

PMID- 24122831
TI  - Good neighbor hypothesis of lignification holds for xylem cells, but not for
      interfascicular fibers.

PMID- 24122832
TI  - A new set of bending Td symmetry coordinates for MX4 molecules.
AB  - The conventional set of Td symmetry coordinates for the bending modes of MX4
      molecules can lead to ambiguous geometries when displacements from equilibrium
      are large. It is proposed here to use internal coordinates that are haversines of
      the bending angles divided by their sum. The A1 representation becomes a
      constant, enabling recovery of the bending angles unambiguously, analytically,
      and without approximation.

PMID- 24122833
TI  - A multilevel analysis of the effects of the Practice Environment Scale of the
      Nursing Work Index on nurse outcomes.
AB  - Few researchers have examined how the components of the Practice Environment
      Scale of the Nursing Work Index (PES-NWI) relate to nurses' well-being at
      multiple organizational levels. The objective of the study was to perform a
      multilevel assessment of the relationships of the PES-NWI subscales with three
      nurse outcomes: job satisfaction, emotional exhaustion, and turnover intentions.
      Additionally, we tested the multilevel factor structure of the PES-NWI. In a
      sample of 699 full-time registered nurses in 79 units and 9 branches of a
      hospital system, relationships of the NWI with nurse outcomes were fairly
      consistent across levels of analysis. However, subscales contributed differently
      to the three outcomes, demonstrating the complexity of environmental influences
      on nurses' work experience.

PMID- 24122834
TI  - Cricopharyngeal achalasia in children: botulinum toxin injection as a tool for
      diagnosis and treatment.
AB  - OBJECTIVES/HYPOTHESIS: Characteristics and outcomes of pediatric patients
      undergoing cricopharyngeus injection with botulinum toxin for the treatment of
      cricopharyngeal achalasia were reviewed. A parental telephone survey was
      performed to assess improvement and satisfaction. STUDY DESIGN: Retrospective
      review of patients who underwent injection of the cricopharyngeus with botulinum
      toxin for cricopharyngeal achalasia. A prospective survey of postoperative
      symptoms and parental satisfaction was also performed. METHODS: After
      institutional review board approval, children with cricopharyngeal achalasia who
      underwent injection with botulinum toxin were identified. Specific parameters
      were recorded for each patient. A survey of the parents' satisfaction and
      subjective improvement was then conducted. RESULTS: Six children were identified
      with cricopharyngeal achalasia, with an age range of 3 months to 10 years.
      Symptoms varied and five of the six children required some form of altered
      nutrition. Preoperative studies varied, and the number of injections ranged from
      one to three per patient. One child had transient worsening of aspiration. Two
      children benefited from injections and went on to myotomy, while four children
      did not require myotomy and their symptoms were treated with injections alone. A
      parental survey was performed via telephone. All parents were satisfied with the
      procedure. Three children were symptom-free, and three children still exhibit
      some dysphagia. CONCLUSIONS: Botulinum toxin injection is a useful tool to help
      diagnose and treat pediatric cricopharyngeal achalasia. More research is needed
      to elucidate optimal dosing, frequency of injections, and when to move on to
      surgical intervention. LEVEL OF EVIDENCE: 4.

PMID- 24122835
TI  - Amplification and over-expression of MAP3K3 gene in human breast cancer promotes
      formation and survival of breast cancer cells.
AB  - Gene amplifications in the 17q chromosomal region are observed frequently in
      breast cancers. An integrative bioinformatics analysis of this region nominated
      the MAP3K3 gene as a potential therapeutic target in breast cancer. This gene
      encodes mitogen-activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which
      has not yet been reported to be associated with cancer-causing genetic
      aberrations. We found that MAP3K3 was amplified in approximately 8-20% of breast
      cancers. Knockdown of MAP3K3 expression significantly inhibited cell
      proliferation and colony formation in MAP3K3-amplified breast cancer cell lines
      MCF-7 and MDA-MB-361 but not in MAP3K3 non-amplified breast cancer cells.
      Knockdown of MAP3K3 expression in MAP3K3-amplified breast cancer cells sensitized
      breast cancer cells to apoptotic induction by TNFalpha and TRAIL, as well as
      doxorubicin, VP-16 and fluorouracil, three commonly used chemotherapeutic drugs
      for treating breast cancer. In addition, ectopic expression of MAP3K3, in
      collaboration with Ras, induced colony formation in both primary mouse embryonic
      fibroblasts and immortalized human breast epithelial cells (MCF-10A). Combined,
      these results suggest that MAP3K3 contributes to breast carcinogenesis and may
      endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore,
      MAP3K3 may be a valuable therapeutic target in patients with MAP3K3-amplified
      breast cancers, and blocking MAP3K3 kinase activity with a small molecule
      inhibitor may sensitize MAP3K3-amplified breast cancer cells to chemotherapy.

PMID- 24122836
TI  - Effect of dosing schemes of amoxicillin on eradication rates of Helicobacter
      pylori with amoxicillin-based triple therapy.
AB  - OBJECTIVES: In standard regimens for Helicobacter pylori infection, amoxicillin
      is dosed twice daily, although the bactericidal effect of amoxicillin depends on
      the %time-above-MIC. We aimed to examine whether dosing schemes of amoxicillin
      influenced eradication rates of amoxicillin-based regimens. METHODS: One hundred
      eighty-seven patients infected with clarithromycin-sensitive strains of H. pylori
      were treated with PPI, clarithromycin 200 mg bid and amoxicillin 750 mg bid, 500
      mg tid or 500 mg qid for 1 week and 125 infected with clarithromycin-resistant
      strains were treated with PPI, metronidazole 250 mg bid and amoxicillin 750 mg
      bid, 500 mg tid or 500 mg qid for 1 week. RESULTS: Eradication rates (ITT) of the
      triple PPI/amoxicillin/clarithromycin therapy with bid, tid and qid dosings of
      amoxicillin were 77.8% (49/63), 93.5% (58/62), and 91.9% (57/62), respectively.
      Those of the triple PPI/amoxicillin/metronidazole therapy were 80.5% (33/41),
      90.5% (38/42), and 95.2% (40/42), respectively. Eradication rates in regimens
      with tid and qid dosing of amoxicillin were higher than those of regimens with
      the bid dosing of amoxicillin. CONCLUSIONS: The dosing scheme of amoxicillin
      significantly influenced eradication rates of triple therapies. Although
      amoxicillin is empirically dosed twice daily, amoxicillin should be dosed at
      least three times daily in amoxicillin-based triple therapies.

PMID- 24122837
TI  - Perinatal management of trisomy 18: a survey of obstetricians in Australia, New
      Zealand and the UK.
AB  - OBJECTIVE: The objective of this study was to explore the attitudes of
      obstetricians in Australia, New Zealand and the UK towards prenatally diagnosed
      trisomy 18 (T18). METHOD: Obstetricians were contacted by email and invited to
      participate in an anonymous electronic survey. RESULTS: Survey responses were
      obtained from 1018/3717 (27%) practicing obstetricians/gynaecologists. Most (60%)
      had managed a case of T18 in the last 2 years. Eighty-five per cent believed that
      T18 was a 'lethal malformation', although 38% expected at least half of liveborn
      infants to survive for more than 1 week. Twenty-one per cent indicated that a
      vegetative existence was the best developmental outcome for surviving children.
      In a case of antenatally diagnosed T18, 95% of obstetricians would provide a
      mother with the option of termination. If requested, 99% would provide maternal
      focused obstetric care (aimed at maternal wellbeing rather than fetal survival),
      whereas 80% would provide fetal-oriented obstetric care (to maximise fetal
      survival). Twenty-eight per cent would never discuss the option of caesarean; 21%
      would always discuss this option. Management options, attitudes and knowledge of
      T18 were associated with location, practice type, gender and religion of
      obstetricians. CONCLUSION: There is variability in obstetricians' attitudes
      towards T18, with significant implications for management of affected
      pregnancies.

PMID- 24122838
TI  - Morphofunctional transformations of the yolk syncytial layer during zebrafish
      development.
AB  - The yolk syncytial layer (YSL) is a provisory extraembryonic structure of teleost
      fishes and representatives of some other taxa with meroblastic cleavage. The YSL
      of teleosts is a symplast with polymorphous polyploid nuclei. It is known to
      perform nutritional, morphogenetic, immune, and, probably, other functions. Data
      about the YSL organization, functioning and regulation is fragmentary. Although
      gene expression patterns and other aspects of YSL functioning have been studied
      in Danio rerio, the morphology of its YSL has not been described in detail. The
      study of zebrafish YSL structure on sequential developmental stages is necessary
      to recognize specific features of this important polyfunctional system in this
      model organism and to extend our knowledge about provisory systems. The thickness
      of the YSL and the distribution of its nuclei are not uniform on each stage and
      change during development. During oblong and sphere stages the internal YSL (I
      YSL) is filled with yolk inclusions; interphase yolk syncytial nuclei (YSN) and
      mitotic asters can be seen. During doming and epiboly the external YSL (E-YSL) is
      thicker than I-YSL. On the subsequent stages the YSL is thickened caudally. The
      dorsal YSL part is thickened during early segmentation stages and becomes the
      thinnest YSL region later. The anterior part of the YSL is thin, but enlarges
      during larval period. The YSN of different size and diverse forms, from regular
      to lobed, are present and form clusters. The number of irregular-shaped nuclei
      increases during development. The YSL thickens in the end of endotrophic and in
      the course of endo-exotrophic period, and its cytoplasm contains numerous yolk
      inclusions. After yolk exhaustion the YSL is flat. As the YSL degrades, the YSN
      become pycnotic, and the YSL remnant probably is cleared by phagocytes.

PMID- 24122839
TI  - Solvent bar microextraction combined with high-performance liquid chromatography
      for preconcentration and determination of pramipexole in biological samples.
AB  - A simple, rapid and sensitive analytical method for preconcentration and
      determination of pramipexole in different biological samples has been developed
      using solvent bar microextraction (SBME) combined with HPLC-UV. The target drugs
      were extracted from 10 mL of basic aqueous sample solution into an organic
      extracting solvent located inside the pores of a polypropylene hollow fiber, then
      back-extracted into an acidified aqueous solution in the lumen of the hollow
      fiber. In order to obtain high extraction efficiency, the effect of different
      variables on the extraction efficiency was studied simultaneously using an
      experimental design. The experimental parameters of SBME were optimized using a
      Box-Behnken design after a Plackett-Burman screening design. Under the optimized
      conditions, an enrichment factor up to 96 was achieved and the relative standard
      deviation of the method was 4.64% (n = 5). The linear range was 0.05-2000 ug/L
      with a correlation coefficient (r) of 0.987. Finally, the applicability of the
      proposed method was evaluated by extraction and determination of pramipexole in
      plasma and urine samples. The results indicated that SBME method has excellent
      clean-up and high preconcentration factor and can serve as a simple and sensitive
      method for analysis of pramipexole in biological samples.

PMID- 24122841
TI  - Opportunities and challenges of combined effect measures based on prioritized
      outcomes.
AB  - Many authors have proposed different approaches to combine multiple endpoints in
      a univariate outcome measure in the literature. In case of binary or time-to
      event variables, composite endpoints, which combine several event types within a
      single event or time-to-first-event analysis are often used to assess the overall
      treatment effect. A main drawback of this approach is that the interpretation of
      the composite effect can be difficult as a negative effect in one component can
      be masked by a positive effect in another. Recently, some authors proposed more
      general approaches based on a priority ranking of outcomes, which moreover allow
      to combine outcome variables of different scale levels. These new combined effect
      measures assign a higher impact to more important endpoints, which is meant to
      simplify the interpretation of results. Whereas statistical tests and models for
      binary and time-to-event variables are well understood, the latter methods have
      not been investigated in detail so far. In this paper, we will investigate the
      statistical properties of prioritized combined outcome measures. We will perform
      a systematical comparison to standard composite measures, such as the all-cause
      hazard ratio in case of time-to-event variables or the absolute rate difference
      in case of binary variables, to derive recommendations for different clinical
      trial scenarios. We will discuss extensions and modifications of the new effect
      measures, which simplify the clinical interpretation. Moreover, we propose a new
      method on how to combine the classical composite approach with a priority ranking
      of outcomes using a multiple testing strategy based on the closed test procedure.

PMID- 24122840
TI  - PROX1 gene variant is associated with fasting glucose change after
      antihypertensive treatment.
AB  - STUDY OBJECTIVE: To assess the relationship of the 33 single nucleotide
      polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in
      genome-wide association studies (GWAS) with glucose response to antihypertensive
      drugs shown to increase risk for hyperglycemia and diabetes. DESIGN: Randomized,
      multicenter clinical trial. PATIENTS: A total of 456 Caucasian men and women with
      uncomplicated hypertension. MEASUREMENTS AND MAIN RESULTS: The Pharmacogenomic
      Evaluation of Antihypertensives Responses study evaluated blood pressure and
      glucose response in uncomplicated hypertensive patients randomized to either
      atenolol or hydrochlorothiazide (HCTZ) monotherapy, followed by combination
      therapy with both agents. Association of these SNPs with atenolol- or HCTZ
      induced glucose response was evaluated in 456 Caucasian patients using linear
      regression adjusting for age, sex, body mass index, baseline glucose, baseline
      insulin, and principal component for ancestry. The SNP rs340874 in the 5' region
      of PROX1 gene was significantly associated with atenolol-induced glucose change
      (p=0.0013). Participants harboring the C allele of this SNP had greater glucose
      elevation after approximately 9 weeks of atenolol monotherapy (beta = +2.39 mg/dl
      per C allele), consistent with the direction of effect in fasting glucose GWAS,
      that showed the C allele is associated with higher fasting glucose. CONCLUSION:
      These data suggest that PROX1 SNP rs340874, discovered in fasting glucose GWAS,
      may also be a pharmacogenetic risk factor for antihypertensive-induced
      hyperglycemia. beta-blockers and thiazides may interact with genetic risk factors
      to increase risk for dysglycemia and diabetes.

PMID- 24122842
TI  - ORX neuroreceptor system and HSP90 are linked to recovery strategies against
      copper toxicity in Thalassoma pavo.
AB  - Fish are particularly sensitive to copper (Cu) because although it is an
      essential metal, it becomes dangerous for aquatic ecosystems, thus accounting for
      physiological alterations. In this study, we investigated Cu effects on
      neurobehavioral activities of Thalassoma pavo and, above all, its recovery
      strategies by evaluating behavioral disturbances, neurodegeneration, and
      expression of heat shock protein (HSP)90 and orexin receptor (ORXR). Ornate
      wrasses exposed to nominal sublethal higher (1.07 mg/l) and lower (0.25 mg/l)
      concentrations of CuCl2.H2O mostly reduced swimming and feeding activities along
      with inducing abnormal behaviors in a dose-dependent manner. Concomitantly, ORXR
      transcripts were mostly upregulated in the diffuse nucleus of the inferior lobe
      (NDLI, + 142%) and the corpus of the cerebellum (CCe, + 243%), whereas HSP90 was
      downregulated only in lateral part of the dorsal telencephalon (Dl, -35%), the
      nucleus glomerulosus (NG; -40%), and the optic tectum (OT; -33%). Interestingly,
      when fish were transferred to Cu-free water, some behaviors were promptly
      rescued, especially in fish previously exposed to the lower Cu concentration.
      This rescuing tendency was confirmed by evident reductions of argyrophilic
      signals in Dl (-67%), NG (-31%), and OT (-42%) of fish exposed to 0.25 mg/l Cu.
      Moreover, transcriptional events of both ORXR and HSP90 were further upregulated
      in order to orchestrate a reactivation of behavioral and neuronal functions.
      Overall, this study highlights, for the first time, new neuronal strategies
      against environmental adverse conditions involving both ORXergic system and HSP90
      as key elements that may assure, at least in part, protection and recovery
      processes against toxic agents.

PMID- 24122843
TI  - HTS-DB: an online resource to publish and query data from functional genomics
      high-throughput siRNA screening projects.
AB  - High-throughput screening (HTS) uses technologies such as RNA interference to
      generate loss-of-function phenotypes on a genomic scale. As these technologies
      become more popular, many research institutes have established core facilities of
      expertise to deal with the challenges of large-scale HTS experiments. As the
      efforts of core facility screening projects come to fruition, focus has shifted
      towards managing the results of these experiments and making them available in a
      useful format that can be further mined for phenotypic discovery. The HTS-DB
      database provides a public view of data from screening projects undertaken by the
      HTS core facility at the CRUK London Research Institute. All projects and screens
      are described with comprehensive assay protocols, and datasets are provided with
      complete descriptions of analysis techniques. This format allows users to browse
      and search data from large-scale studies in an informative and intuitive way. It
      also provides a repository for additional measurements obtained from screens that
      were not the focus of the project, such as cell viability, and groups these data
      so that it can provide a gene-centric summary across several different cell lines
      and conditions. All datasets from our screens that can be made available can be
      viewed interactively and mined for further hit lists. We believe that in this
      format, the database provides researchers with rapid access to results of large
      scale experiments that might facilitate their understanding of genes/compounds
      identified in their own research. DATABASE URL:
      http://hts.cancerresearchuk.org/db/public.

PMID- 24122844
TI  - Incidence and survival patterns of cranial chordoma in the United States.
AB  - OBJECTIVES/HYPOTHESIS: To determine trends in survival patterns for cranial
      chordoma in the United States. STUDY DESIGN: A cross-sectional analysis of a
      national healthcare database. METHODS: All cases of microscopically confirmed
      cranial chordoma between 1973 and 2009 from the Surveillance, Epidemiology, and
      End Results (SEER) program of the National Cancer Institute were examined. Age
      adjusted incidence and survival rates were calculated and stratified by
      treatment. Additionally, in order to assess trends over time, comparisons in
      survival were conducted for 3 calendar year cohorts: 1975 to 1984, 1985 to 1994,
      and 1995 to 2004. RESULTS: A total of 594 cases of microscopically confirmed
      chordoma involving cranial sites were identified, which accounted for 42% of all
      chordomas. Age-adjusted incidence rate (IR) of all chordomas was 0.089 per
      100,000. Overall median survival time with surgery plus radiation was 9.2 years.
      Age and treatment modality were found to influence patient survival.
      Specifically, age > 50 years was associated with a significant increase in
      mortality rate (P < .05). Five-year survival for the 1975 to 1984, 1985 to 1994,
      and 1995 to 2004 cohort was 48.5%, 73.0%, and 80.7%, respectively, with improved
      survival in the more recent cohorts (P < 0.01). CONCLUSION: This study provides
      new data regarding survival patterns of cranial chordoma in the United States,
      with a trend toward improvement in survival in recent decades.

PMID- 24122845
TI  - Histopathological findings on Carassius auratus hepatopancreas upon exposure to
      acrylamide: correlation with genotoxicity and metabolic alterations.
AB  - Acrylamide is an amide used in several industrial applications making it easily
      discharged to aquatic ecosystems. The toxicity of acrylamide to aquatic organisms
      is scarcely known, although previous studies with murine models provided evidence
      for deleterious effects. To assess the effects of acrylamide to freshwater fish,
      goldfish (Carassius auratus L.) were exposed to several concentrations of
      waterborne acrylamide and analysed for genotoxic damage, alterations to
      detoxifying enzymes and histopathology. Results revealed a dose-dependent
      increase in total DNA strand breakage, the formation of erythrocytic nuclear
      abnormalities and in the levels of hepatic cytochrome P4501A (CYP1A) and
      glutathione S-transferase (GST) activity. In addition, acrylamide induced more
      histopathological changes to pancreatic acini than to the hepatic parenchyma,
      regardless of exposure concentration, whereas hepatic tissue only endured
      significant alterations at higher concentrations of exposure. Thus, results
      confirm the genotoxic potential of acrylamide to fish and its ability to induce
      CYP1A, probably as a direct primary defence mechanism. This strongly suggests the
      substance's pro-mutagenic potential in fish, similarly to what is known for
      rodents. However, the deleterious effects observed in the pancreatic acini, more
      severe than in the liver, could indicate a specific, albeit unknown toxic
      mechanism of acrylamide to fish that overran the organism's metabolic defences
      against a chemical agent rather than causing a general systemic failure.

PMID- 24122846
TI  - Novel Death Defying Domain in Met entraps the active site of caspase-3 and blocks
      apoptosis in hepatocytes.
AB  - Met, the transmembrane tyrosine kinase receptor for hepatocyte growth factor
      (HGF), is known to function as a potent antiapoptotic mediator in normal and
      neoplastic cells. Herein we report that the intracellular cytoplasmic tail of Met
      has evolved to harbor a tandem pair of caspase-3 cleavage sites, which bait,
      trap, and disable the active site of caspase-3, thereby blocking the execution of
      apoptosis. We call this caspase-3 cleavage motif the Death Defying Domain (DDD).
      This site consists of the following sequence: DNAD-DEVD-T (where the hyphens
      denote caspase cleavage sites). Through functional and mechanistic studies, we
      show that upon DDD cleavage by caspase-3 the resulting DEVD-T peptide acts as a
      competitive inhibitor and entraps the active site of caspase-3 akin to DEVD-CHO,
      which is a potent, synthetic inhibitor of caspase-3 activity. By gain- and loss
      of-function studies using restoration of DDD expression in DDD-deficient
      hepatocytic cells, we found that both caspase-3 sites in DDD are necessary for
      inhibition of caspase-3 and promotion of cell survival. Employing mutagenesis
      studies, we show that DDD could operate independently of Met's enzymatic activity
      as determined by using kinase-dead human Met mutant constructs. Studies of both
      human liver cancer tissues and cell lines uncovered that DDD cleavage and
      entrapment of caspase-3 by DDD occur in vivo, further proving that this site has
      physiological and pathophysiological relevance. CONCLUSION: Met can directly
      inhibit caspase-3 by way of a novel mechanism and promote hepatocyte survival.
      The results presented here will further our understanding of the mechanisms that
      control not only normal tissue homeostasis but also abnormal tissue growth such
      as cancer and degenerative diseases in which apoptotic caspases are at play.

PMID- 24122847
TI  - Serum IgA to Epstein-Barr virus early antigen-diffuse identifies Hodgkin's
      lymphoma.
AB  - Hodgkin's lymphoma is associated with immune dysregulation. Immune impairment
      often results in aberrant immune responses and lytic reactivation of ubiquitous
      Herpesviruses, such as Epstein-Barr virus (EBV) in mucosal tissues. Accordingly,
      the specificity of IgA to EBV early lytic antigens, which are important for
      reactivation, was evaluated to determine Hodgkin's lymphoma-specific sero
      reactive patterns. Sera from 42 patients with Hodgkin's lymphoma were compared to
      sera from 17 patients with infectious mononucleosis (IM), another EBV-related
      condition that often presents in a similar manner; and to sera from 15 healthy
      EBV-seropositive subjects. Flow cytometry analysis demonstrated that like IM
      sera, most Hodgkin's lymphoma sera contained IgA that labeled cells expressing
      EBV early lytic antigens whereas healthy EBV-seropositive sera did not. Further
      evaluation to distinguish Hodgkin's lymphoma from IM showed that IgA in most
      Hodgkin's lymphoma, irrespective of the presence of EBV in primary tumors,
      detected only modified forms of EBV lytic Early Antigen-Diffuse (EA-D) while IM
      sera detected the un-modified form as well, further supporting the presence of
      immune dysregulation in Hodgkin's lymphoma patients. This IgA pattern
      distinguished Hodgkin's lymphoma from IM sera with a sensitivity of 92.9%,
      specificity 100%, positive predictive value 100%, and negative predictive value
      85%. Our findings lay the groundwork for additional scientific and clinical
      investigation, particularly into the potential for developing Hodgkin's lymphoma
      associated diagnostic and prognostic biomarkers.

PMID- 24122848
TI  - Antiviral treatment for hepatitis C virus infection is associated with improved
      renal and cardiovascular outcomes in diabetic patients.
AB  - Hepatitis C virus (HCV) infection is causally associated with insulin resistance
      and diabetes mellitus. This population-based cohort study aimed to investigate
      whether antiviral therapy for HCV infection was associated with improved clinical
      outcomes related to diabetes. From the Taiwan National Health Insurance Research
      Database, 2,267,270 Taiwanese residents diagnosed with diabetes mellitus were
      screened for eligibility. HCV infection was defined by a specific diagnosis code
      and measurement of serum antibody. After excluding patients with serious
      comorbidity, we enrolled a total of 1,411 eligible patients who received
      pegylated interferon plus ribavirin (treated cohort), and matched them 1:1 with
      1,411 untreated controls by propensity scores (untreated cohort). We also matched
      the treated cohort 1:4 with 5,644 diabetic patients without HCV infection
      (uninfected cohort). Participants were followed up for the occurrence of endstage
      renal disease (ESRD), ischemic stroke, and acute coronary syndrome (ACS) after
      receiving antiviral treatment or the corresponding calendar date. From 2003 to
      2011, the 8-year cumulative incidences of ESRD in the treated, untreated, and
      uninfected cohorts were 1.1% (95% confidence interval [CI], 0.3-2.0%), 9.3% (95%
      CI, 5.9-12.7%), and 3.3% (95% CI, 2.3-4.3%), respectively (P < 0.001); those of
      stroke were 3.1% (95% CI, 1.1-5.0%), 5.3% (95% CI, 3.0-7.5%), and 6.1% (95% CI,
      4.8-7.4%), respectively (P = 0.01); and those for ACS were 4.1% (95% CI, 2.1
      6.1%), 6.6% (95% CI, 3.7-9.5%), and 7.4% (95% CI, 5.9-9.0%), respectively (P =
      0.05). As compared with the untreated cohort, antiviral treatment was associated
      with multivariate-adjusted hazard ratios of 0.16 (95% CI, 0.07-0.33%) for ESRD,
      0.53 (95% CI, 0.30-0.93) for ischemic stroke, and 0.64 (95% CI, 0.39-1.06) for
      ACS. CONCLUSION: Antiviral treatment for HCV infection is associated with
      improved renal and cardiovascular outcomes in diabetic patients.

PMID- 24122849
TI  - Utilization of bevacizumab in US elderly patients with colorectal cancer
      receiving chemotherapy.
AB  - OBJECTIVE: Bevacizumab, the first FDA-approved anti-angiogenesis agent, has been
      used for metastatic colorectal cancer since 2004. This study evaluated the
      utilization of bevacizumab among elderly metastatic colorectal cancer patients in
      the United States. METHODS: Using Surveillance and Epidemiology and End Results
      (SEER)-Medicare data, this retrospective cohort study consisted of individuals
      aged 65 years or older with a colorectal cancer diagnosis between 2005 and 2009,
      who received chemotherapy any time through 2010. This included patients with
      newly diagnosed metastatic colorectal cancer and patients who progressed from
      initially diagnosed earlier-stage disease. We ascertained comorbid conditions
      using ICD-9 codes and conducted logistic regression to identify patients'
      characteristics associated with bevacizumab use. RESULTS: A total of 8645
      patients were identified (mean age 74 years; 52% male); 57% of patients received
      bevacizumab with initially diagnosed metastatic colorectal cancer and 44% of
      patients with treated progressive or recurrent disease. After adjusting for other
      covariates, we found that patients aged >=80 years were less likely to receive
      bevacizumab compared with those aged 65-69 years (odds ratio (OR), 0.64 (95%
      confidence interval (CI): 0.57-0.73)), or if they had evidence of comorbid
      cardiomyopathy/congestive heart failure (OR, 0.82 (CI: 0.70-0.95)) or arrhythmic
      disorder (OR, 0.85 (CI: 0.75-0.96)). Adoption of bevacizumab into practice was
      rapid following its approval, and the use increased from 36% to 40% from 2005 to
      2010 (p = 0.013). There were significant regional variations in bevacizumab use.
      CONCLUSIONS: Despite rapid uptake since its original approval, there appears to
      be low use of bevacizumab in elderly metastatic colorectal cancer patients in the
      United States. Regional variations and the strong effects of age and comorbidity
      suggest lack of consensus among oncologists regarding benefits and risks of
      bevacizumab in elderly patients.

PMID- 24122850
TI  - What do Canadian uro-oncologists believe patients should know about androgen
      deprivation therapy?
AB  - INTRODUCTION: Patients prescribed luteinizing hormone-releasing hormone agonists
      for androgen deprivation therapy (ADT) have significant misconceptions about
      treatment side effects and how to manage them. We surveyed a subset of Canadian
      physicians about what they think is important information to tell patients
      starting on ADT to determine the degree to which there is consensus of opinion.
      METHOD: A questionnaire about ADT side effects and management strategies was
      distributed to physicians-urologists, radiation oncologists, and medical
      oncologists - actively practicing within cancer and urology centers in the
      Canadian provinces of British Columbia, Alberta, Ontario, and the Maritime
      Provinces. RESULT: A total of 75 physicians filled out the survey. Physicians
      agreed that osteoporosis, erectile dysfunction, hot flashes, loss of libido, and
      loss of muscle mass were drug responses that were essential or important to warn
      patients about. However, for six commonly reported side effects (i.e. depression,
      diabetes, elevated cholesterol, anemia, delayed or absent orgasm, and genital
      shrinkage), physicians showed great variance, with less than 60% agreeing on
      whether to discuss these topics or not. CONCLUSION: There is little consensus
      among physicians regarding what to tell patients when prescribing this treatment.
      The lack of agreement among physicians may partially explain the lack of
      awareness of ADT side effects by patients and partners. The current findings may
      help guide strategies for the design, evaluation, and implementation of
      educational interventions for both physicians and patients that will better
      prepare patients to recognize, adapt to, and overcome ADT side effects.

PMID- 24122852
TI  - Advances in membrane emulsification. Part B: recent developments in modelling and
      scale-up approaches.
AB  - Membrane emulsification is a promising process for formulating emulsions and
      particulates. It offers many advantages over conventional 'high-shear' processes
      with narrower size distribution products, higher batch repeatability and lower
      energy consumption commonly demonstrated at a small scale. Since the process was
      first introduced around 25 years ago, understanding of the underlying mechanisms
      involved during microstructure formation has advanced significantly leading to
      the development of modelling approaches that predict processing output; e.g.
      emulsion droplet size and throughput. The accuracy and ease of application of
      these models is important to allow for the development of design equations which
      can potentially facilitate scale-up of the process and meet the manufacturer's
      specific requirements. Part B of this review considers the advantages and
      disadvantages of a variety of models developed to predict droplet size, flow
      behaviour and other phenomena (namely droplet-droplet interactions), with
      presentation of the appropriate formulae where necessary. Furthermore, the
      advancement of the process towards an industrial scale is also highlighted with
      additional recommendations by the authors for future work.

PMID- 24122853
TI  - Associations between sleep duration and prevalence of cardiovascular events.
AB  - BACKGROUND: Data regarding the associations between sleep duration and clinical
      cardiovascular (CV) events are limited. We aimed to analyze any associations
      between self-reported sleep duration and CV events. HYPOTHESIS METHODS: This is a
      cross-sectional analysis of nationally representative population of
      noninstitutionalized US civilians recruited in the 2007 to 2008 National Health
      and Nutrition Examination Survey. This is a questionnaire-based study including
      only those subjects who answered questions on sleep duration and CV events. The
      main outcome measures were prevalence of congestive heart failure, myocardial
      infarction, stroke, coronary artery disease, and angina. RESULTS: After logistic
      regression analysis, significant associations between sleep duration and
      prevalence of stroke, myocardial infarction, congestive heart failure, coronary
      artery disease, and angina were found. There was a statistically significant
      increase in stroke in those with <6 hours of sleep (odds ratio [OR]: 2.0111, 95%
      confidence interval [CI]: 1.4356-2.8174), in myocardial infarction in those with
      <6 hours of sleep (OR: 2.0489, 95% CI: 1.4878-2.8216), in congestive heart
      failure in those with <6 hours of sleep (OR: 1.6702, 95% CI: 1.1555 to 2.4142),
      in coronary artery disease in those with >8 hours of sleep (OR: 1.1914, 95% CI:
      1.0712-3.4231), and in angina in those with >8 hours of sleep (OR: 2.0717, 95%
      CI: 1.0497-4.0887). CONCLUSIONS: The results of this cross-sectional analysis
      suggest that sleep duration may be associated with the prevalence of various CV
      events.

PMID- 24122851
TI  - Ultra-deep T cell receptor sequencing reveals the complexity and intratumour
      heterogeneity of T cell clones in renal cell carcinomas.
AB  - The recognition of cancer cells by T cells can impact upon prognosis and be
      exploited for immunotherapeutic approaches. This recognition depends on the
      specific interaction between antigens displayed on the surface of cancer cells
      and the T cell receptor (TCR), which is generated by somatic rearrangements of
      TCR alpha- and beta-chains (TCRb). Our aim was to assess whether ultra-deep
      sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell
      renal cell carcinoma (ccRCC) samples can provide insights into the clonality and
      heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display
      extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was
      extracted from two to four tumour regions from each of four primary ccRCCs and
      was analysed by ultra-deep TCR sequencing. In parallel, tumour infiltration by
      CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and
      correlated with TCR-sequencing data. A polyclonal T cell repertoire with 367-16
      289 (median 2394) unique TCRb sequences was identified per tumour region. The
      frequencies of the 100 most abundant T cell clones/tumour were poorly correlated
      between most regions (Pearson correlation coefficient, -0.218 to 0.465). 3-93% of
      these T cell clones were not detectable across all regions. Thus, the clonal
      composition of T cell populations can be heterogeneous across different regions
      of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR
      inhibitor, which could suggest that therapy can influence adaptive tumour
      immunity. These data show that ultra-deep TCR-sequencing technology can be
      applied directly to DNA extracted from unfractionated tumour samples, allowing
      novel insights into the clonality of T cell populations in cancers. These were
      polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on
      mechanisms of cancer immunity and the efficacy of immunotherapy approaches.

PMID- 24122854
TI  - Sonographic fetal weight estimation - is there more to it than just fetal
      measurements?
AB  - OBJECTIVES: The primary aim of this study was to evaluate the effects of
      different maternal, fetal, and examiner related factors on the accuracy of
      sonographic fetal weight estimation (SFWE). METHODS: A retrospective cohort study
      analyzing 9064 SFWEs performed within 1 week prior to delivery, including
      singleton pregnancies with a gestational age of 37 to 42 weeks, was recorded at
      one medical center from January 2004 to September 2011. Predicted birth weights
      were calculated according to models by Sabbagha et al., Hadlock et al., and Combs
      et al. and were compared with the actual birth weight. Effects of different
      factors on SFWE accuracy were assessed. The systematic error, random error, and
      mean absolute percentage error were used as measures of accuracy. RESULTS: High
      maternal weight, height, body mass index, multiparity, older maternal age,
      diabetes, and fetal male sex were associated with underestimation of SFWE (P <
      0.05). Fetal presentation and the sonographer's experience influenced SFWE
      differently using various models. The amniotic fluid index did have a significant
      effect on SFWE. Overall, more than 90% of the systematic errors were unaccounted
      for in the factors we assessed. CONCLUSIONS: Many maternal and fetal factors
      significantly influence the SFWE; nevertheless, most errors are probably due to
      inherent problems in SFWE formulas.

PMID- 24122855
TI  - Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese
      patients hospitalized in an intensive care unit.
AB  - The study objective was to evaluate meropenem pharmacokinetics and
      pharmacodynamics in morbid obesity. Nine patients hospitalized in an intensive
      care unit with a body mass index >=40 kg/m(2) received meropenem 500 mg or 1 g
      q6h, infused over 0.5 hours. Pharmacokinetic parameters were estimated, and Monte
      Carlo simulations were performed for 5 dosing regimens (500 mg q8h, 1 g q8h, 2 g
      q8h, 500 mg q6h, 1 g q6h) infused over 0.5 and 3 hours. Probability of target
      attainment (PTA) was calculated using fT > MIC of 40% and 54%. Total body weight
      and body mass index were 152.3 +/- 31.0 kg and 54.7 +/- 8.6 kg/m(2) ,
      respectively. Volume of distribution of the central compartment was 13.3 +/- 6.7
      L, volume of distribution at steady-state was 37.4 +/- 14.7 L, and systemic
      clearance was 10.2 +/- 5.0 L/h. At an MIC of 2 ug/mL, PTA was >=90% for 4/5 and
      2/5 regimens infused over 0.5 hours and for 5/5 and 4/5 regimens infused over 3
      hours at 40% and 54% fT > MIC, respectively. Standard doses achieve adequate
      exposures for susceptible bacteria at a pharmacodynamic target of 40% fT > MIC.
      Higher doses or prolonged infusion regimens are needed at the higher
      pharmacodynamic target. 

PMID- 24122857
TI  - Clinical pharmacists as key members of the patient-centered medical home: an
      opinion statement of the Ambulatory Care Practice and Research Network of the
      American College of Clinical Pharmacy.
AB  - The American College of Clinical Pharmacy (ACCP) Ambulatory Care Practice
      Research Network (PRN) considers the role of clinical pharmacists to be
      fundamental to the success of the Patient-Centered Medical Home (PCMH) model.
      Within the PCMH, pharmacists can improve the health of populations by
      participating in activities that optimize medication management. Multiple
      published articles support clinical pharmacist involvement in the PCMH with
      regard to promotion of team-based care, enhanced access, care coordination, and
      improved quality and safety of care. A survey of clinical pharmacist members of
      ACCP who operate in such a model depict a variety of activities, with some
      members pioneering new and innovative ways to practice clinical pharmacy.
      Although this is a significant opportunity for pharmacists in the primary care
      setting, a unified vision of pharmacy services is needed. It is our hope that
      with continued efforts focused on obtaining national provider status, clinical
      pharmacy can use the PCMH model to solidify the future of primary care pharmacy.
      The following is an opinion statement of the ACCP Ambulatory Care PRN regarding
      the vital role of clinical pharmacists in the PCMH. 

PMID- 24122856
TI  - A quantitative analysis of the polyamine in lung cancer patient fingernails by LC
      ESI-MS/MS.
AB  - A quantitative analysis of polyamines in lung cancer patient fingernails by the
      combination of 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole
      derivatives and liquid chromatography-electrospray ionization tandem mass
      spectrometry is described. The reaction of the reagent with eight kinds of
      polyamines, that is, N(1) -acetylputrescine (N(1) -actPUT), N(8) 
      acetylspermidine, N(1) -acetylspermine, 1,3-diaminopropane, putrescine (PUT),
      cadaverine, spermidine and spermine (SPM) effectively occurs at 60  degrees C for
      30 min. The detection limits (signal-to-noise ratio 5) were 5-100 fmol. A good
      linearity was achieved from the calibration curves, which was obtained by
      plotting the peak area ratios of the analytes relative to the internal standard
      (IS), that is, 1,6-diaminohexane, vs the injected amounts of polyamines (r(2)  >
      0.996), and the intra-day and inter-day assay precisions were <9.84%.
      Furthermore, the recoveries (%) of the polyamines spiked in the human fingernails
      were 89.14-110.64. The present method was applied to human fingernail samples
      from 17 lung cancer patients and 39 healthy volunteers. The polyamine
      concentration was different based on the gender, that is, the N(1) -actPUT and
      PUT contents were 3.10 times and 2.56 times higher in healthy men than in women,
      respectively. Additionally, in the lung cancer patient group, as compared with
      the healthy volunteers, the concentrations of SPM had a statistically significant
      (p < 0.05) correlation. Therefore, because the proposed method provides a good
      mass accuracy and the trace detection of the polyamines in human fingernails,
      this analytical technique could be a noninvasive technique to assist in the
      diagnosis and assessment of disease activity in lung cancer patients.

PMID- 24122858
TI  - When is the best timing for the second implant in pediatric bilateral cochlear
      implantation?

PMID- 24122859
TI  - Incorporating adverse event relatedness into dose-finding clinical trial designs.
AB  - Dose-finding designs estimate the dose level of a drug based on observed adverse
      events. Relatedness of the adverse event to the drug has been generally ignored
      in all proposed design methodologies. These designs assume that the adverse
      events observed during a trial are definitely related to the drug, which can lead
      to flawed dose-level estimation. We incorporate adverse event relatedness into
      the so-called continual reassessment method. Adverse events that have 'doubtful'
      or 'possible' relationships to the drug are modelled using a two-parameter
      logistic model with an additive probability mass. Adverse events 'probably' or
      'definitely' related to the drug are modelled using a cumulative logistic model.
      To search for the maximum tolerated dose, we use the maximum estimated toxicity
      probability of these two adverse event relatedness categories. We conduct a
      simulation study that illustrates the characteristics of the design under various
      scenarios. This article demonstrates that adverse event relatedness is important
      for improved dose estimation. It opens up further research pathways into
      continual reassessment design methodologies.

PMID- 24122860
TI  - A catch-up validation study of an in vitro skin irritation test method using
      reconstructed human epidermis LabCyte EPI-MODEL24.
AB  - Three validation studies were conducted by the Japanese Society for Alternatives
      to Animal Experiments in order to assess the performance of a skin irritation
      assay using reconstructed human epidermis (RhE) LabCyte EPI-MODEL24 (LabCyte EPI
      MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J-TEC), and the
      results of these studies were submitted to the Organisation for Economic Co
      operation and Development (OECD) for the creation of a Test Guideline (TG). In
      the summary review report from the OECD, the peer review panel indicated the need
      to resolve an issue regarding the misclassification of 1-bromohexane. To this
      end, a rinsing operation intended to remove exposed chemicals was reviewed and
      the standard operating procedure (SOP) revised by J-TEC. Thereafter, in order to
      confirm general versatility of the revised SOP, a new validation management team
      was organized by the Japanese Center for the Validation of Alternative Methods
      (JaCVAM) to undertake a catch-up validation study that would compare the revised
      assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010).
      The catch-up validation and supplementary studies for LabCyte EPI-MODEL24 SIT
      using the revised SOPs were conducted at three laboratories. These results showed
      that the revised SOP of LabCyte EPI-MODEL24 SIT conformed more accurately to the
      classifications for skin irritation under the United Nations Globally Harmonised
      System of Classification and Labelling of Chemicals (UN GHS), thereby
      highlighting the importance of an optimized rinsing operation for the removal of
      exposed chemicals in obtaining consistent results from in vitro skin irritation
      assays.

PMID- 24122861
TI  - Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced
      murine autochthonous hepatocellular carcinoma.
AB  - Immunization with effective cancer vaccines can offer a much needed adjuvant
      therapy to fill the treatment gap after liver resection to prevent relapse of
      hepatocellular carcinoma (HCC). However, current HCC cancer vaccines are mostly
      based on native shared-self/tumor antigens that are only able to induce weak
      immune responses. In this study we investigated whether the HCC-associated
      self/tumor antigen of alpha-fetoprotein (AFP) could be engineered to create an
      effective vaccine to break immune tolerance and potently activate CD8 T cells to
      prevent clinically relevant carcinogen-induced autochthonous HCC in mice. We
      found that the approach of computer-guided methodical epitope-optimization
      created a highly immunogenic AFP and that immunization with lentivector
      expressing the epitope-optimized AFP, but not wild-type AFP, potently activated
      CD8 T cells. Critically, the activated CD8 T cells not only cross-recognized
      short synthetic wild-type AFP peptides, but also recognized and killed tumor
      cells expressing wild-type AFP protein. Immunization with lentivector expressing
      optimized AFP, but not native AFP, completely protected mice from tumor challenge
      and reduced the incidence of carcinogen-induced autochthonous HCC. In addition,
      prime-boost immunization with the optimized AFP significantly increased the
      frequency of AFP-specific memory CD8 T cells in the liver that were highly
      effective against emerging HCC tumor cells, further enhancing the tumor
      prevention of carcinogen-induced autochthonous HCC. CONCLUSIONS: Epitope
      optimization is required to break immune tolerance and potently activate AFP
      specific CD8 T cells, generating effective antitumor effect to prevent clinically
      relevant carcinogen-induced autochthonous HCC in mice. Our study provides a
      practical roadmap to develop effective human HCC vaccines that may result in an
      improved outcome compared to the current HCC vaccines based on wild-type AFP.

PMID- 24122862
TI  - Simultaneous detection of hepatitis C virus and interferon stimulated gene
      expression in infected human liver.
AB  - Approximately 50% of patients with chronic hepatitis C (CHC) have ongoing
      expression of interferon stimulated genes (ISGs) in the liver. It is unclear why
      this endogenous antiviral response is inefficient in eradicating the infection.
      Several viral escape strategies have been identified in vitro, including
      inhibition of interferon (IFN) induction and ISG messenger RNA (mRNA)
      translation. The in vivo relevance of these mechanisms is unknown, because
      reliable methods to identify hepatitis C virus (HCV)-infected cells in human
      liver are lacking. We developed a highly sensitive in situ hybridization (ISH)
      system capable of HCV RNA and ISG mRNA detection in human liver biopsies and
      applied it to study the interaction of HCV with the endogenous IFN system. We
      simultaneously monitored HCV RNA and ISG mRNA using HCV isolate- and ISG mRNA
      specific probes in liver biopsy sections from 18 CHC patients. The signals were
      quantified at the single-cell resolution in a series of random high-power fields.
      The proportion of infected hepatocytes ranged from 1%-54% and correlated with
      viral load, but not with HCV genotype or ISG expression. Infected cells occurred
      in clusters, pointing to cell-to-cell spread as the predominant mode of HCV
      transmission. ISG mRNAs were readily detected in HCV-infected cells, challenging
      previously proposed mechanisms of viral interference with the immune system.
      Conversely, infected cells and neighboring cells showed increased ISG mRNA
      levels, demonstrating that the stimulus driving ISG expression originates from
      HCV-infected hepatocytes. CONCLUSION: HCV infection in human hepatocytes during
      CHC does not efficiently interfere with IFN induction, IFN signaling, or
      transcription of ISG mRNA.

PMID- 24122863
TI  - A case of myocarditis following neonatal meningitis caused by coxsackievirus B1
      in spite of intravenous immunoglobulin treatment.
AB  - Enteroviral infection is one of the most common neonatal infections, and most
      patients recover without complications. This report describes a neonate who
      experienced meningitis followed by myocarditis. A 4-day-old boy was admitted with
      fever, diagnosed with enteroviral meningitis and treated with intravenous
      immunoglobulin (IVIG). However, myocarditis was subsequently diagnosed in spite
      of IVIG treatment, and coxsackievirus B1 (CXB1) was revealed as a cause. A left
      ventricular aneurysm persisted even though the patient recovered with repeated
      high-dose IVIG treatment and cardiac supportive care. This report describes a
      rare case where myocarditis developed several days after a diagnosis of CXB1
      meningitis in spite of IVIG treatment. It is important to pay attention to the
      patient's clinical condition until the end of the second viremia of enterovirus
      and to consider high-dose IVIG treatment when treating enteroviral infections for
      neonates. 

PMID- 24122864
TI  - Geometrical and optical benchmarking of copper guanidine-quinoline complexes:
      insights from TD-DFT and many-body perturbation theory.
AB  - We report a comprehensive computational benchmarking of the structural and
      optical properties of a bis(chelate) copper(I) guanidine-quinoline complex. Using
      various (TD-)DFT flavors a strong influence of the basis set is found. Moreover,
      the amount of exact exchange shifts metal-to-ligand bands by 1 eV through the
      absorption spectrum. The BP86/6-311G(d) and B3LYP/def2-TZVP functional/basis set
      combinations were found to yield results in best agreement with the experimental
      data. In order to probe the general applicability of TD-DFT to excitations of
      copper bis(chelate) charge-transfer (CT) systems, we studied a small model system
      that on the one hand is accessible to methods of many-body perturbation theory
      (MBPT) but still contains simple guanidine and imine groups. These calculations
      show that large quasiparticle energies of the order of several electronvolts are
      largely offset by exciton binding energies for optical excitations and that TD
      DFT excitation energies deviate from MBPT results by at most 0.5 eV, further
      corroborating the reliability of our TD-DFT results. The latter result in a
      multitude of MLCT bands ranging from the visible region at 3.4 eV into the UV at
      5.5 eV for the bis(chelate) complex. Molecular orbital analysis provided insight
      into the CT within these systems but gave mixed transitions. A meaningful
      transition assignment is possible, however, by using natural transition orbitals.
      Additionally, we performed a thorough conformational analysis as the correct
      description of the copper coordination is crucial for the prediction of optical
      spectra. We found that DFT identifies the correct conformational minimum and that
      the MLCTs are strongly dependent on the torsion of the chelate angles at the
      copper center. From the results, it is concluded that extensive benchmarking
      allows for the quantitative analyses of the CT behavior of copper bis(chelate)
      complexes within TD-DFT.

PMID- 24122866
TI  - Oral vaccination with a liposome-encapsulated influenza DNA vaccine protects mice
      against respiratory challenge infection.
AB  - It is well accepted that vaccination by oral administration has many advantages
      over injected parenteral immunization. The present study focuses on whether oral
      vaccination with a DNA vaccine could induce protective immunity against
      respiratory challenge infection. The M1 gene of influenza A virus was used to
      construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector.
      The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro
      and in vivo expression of M1 gene was observed in the cell line and in the
      intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that
      this type of oral DNA vaccination was capable of inducing both humoral and
      cellular immune responses, together with an augmentation of IFN-gamma production.
      In addition, oral vaccination with liposome-encapsulated DNA vaccine could
      protect the mice against respiratory challenge infection. These results suggest
      that gastrointestinal tract, a constituent member of the common mucosal immune
      system, is a potent candidate applicable as a DNA vaccine route against virus
      respiratory diseases.

PMID- 24122865
TI  - Hydrogen peroxide as a damage signal in tissue injury and inflammation: murderer,
      mediator, or messenger?
AB  - Tissue injury and inflammation are associated with increased production of
      reactive oxygen species (ROS), which have the ability to induce oxidative injury
      to various biomolecules resulting in protein dysfunction, genetic instability, or
      cell death. However, recent observations indicate that formation of hydrogen
      peroxide (H2 O2 ) during tissue injury is also an essential feature of the
      ensuing wound healing response, and functions as an early damage signal to
      control several critical aspects of the wound healing process. Because innate
      oxidative wound responses must be tightly coordinated to avoid chronic
      inflammation or tissue injury, a more complete understanding is needed regarding
      the origins and dynamics of ROS production, and their critical biological
      targets. This prospect highlights the current experimental evidence implicating
      H2 O2 in early epithelial wound responses, and summarizes technical advances and
      approaches that may help distinguish its beneficial actions from its more
      deleterious actions in conditions of chronic tissue injury or inflammation.

PMID- 24122867
TI  - U.S. practice variations in the treatment of chronic laryngopharyngeal
      neuropathy.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate differences in evaluation and workup of
      laryngopharyngeal neuropathy in a population of general otolaryngologists and
      fellowship-trained laryngologists. STUDY DESIGN: Survey. METHODS: Members of the
      American Laryngological Association (ALA) and a general otolaryngologist database
      from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) were
      surveyed. A questionnaire was e-mailed or mailed to 179 members of the ALA and
      900 members from the AAO-HNS database. RESULTS: Responses were received from 43
      subjects in the ALA group (24.5%) and 96 in the AAO-HNS database group (10.6%).
      Compared to the general otolaryngologists surveyed, ALA members were found to be
      more likely to practice in academics (79.6% vs. 6.6%) and to have been fellowship
      trained (79.5% vs. 16.5%). Among the general otolaryngologists, 44.6% reported
      being unfamiliar with laryngopharyngeal neuropathy compared to 0% from the ALA
      group (P < .0001). After accounting for the respondents unfamiliar with the
      condition, the general otolaryngologists reported being less comfortable in
      diagnosing laryngopharyngeal neuropathy (P < .0001) and were more concerned about
      the over-diagnosis of laryngopharyngeal reflux when compared to the ALA (P =
      .0030). CONCLUSION: General otolaryngologists and fellowship-trained
      laryngologist have several differences in the knowledge, workup, and treatment of
      chronic laryngopharyngeal neuropathy. This may translate to unnecessary
      treatments and tests for effected patients and should be addressed with further
      education targeting general otolaryngologists. LEVEL OF EVIDENCE: 4.

PMID- 24122868
TI  - Assessment of toxicity test endpoints for freshwater mussel larvae (glochidia).
AB  - The objectives of the present study were to determine if the viability of
      freshwater mussel larvae (glochidia) is an ecologically relevant endpoint for
      toxicity tests and to define the appropriate duration of those tests. The authors
      assessed 1) how viability (the shell closure response to sodium chloride)
      compares with infectivity (ability to attach to a host fish and successfully
      metamorphose to the juvenile stage), and 2) the decline of viability and
      infectivity over time after glochidia were released from female mussels.
      Glochidia of 7 mussel species were isolated from females, placed in water, and
      subsampled daily for 2 d to 5 d. Viability, when >=90%, was generally a good
      predictor of infectivity; however, when viability was <90%, infectivity was often
      disproportionately low, especially for glochidia collected near the end of the
      brooding period. Viability and infectivity declined more rapidly in natural water
      and sediment compared to reconstituted water. Following 24-h exposure to a
      toxicant (sodium chloride or copper), infectivity of the viable glochidia did not
      differ among concentrations of toxicants. The results indicate that viability is
      a valid proxy for infectivity and an ecologically relevant endpoint for standard
      toxicity tests with freshwater mussels for any test duration with control
      viability >90%.

PMID- 24122869
TI  - Fistula rates after salvage laryngectomy: comparing pectoralis myofascial and
      myocutaneous flaps.
AB  - OBJECTIVES/HYPOTHESIS: Salvage laryngectomy after failed organ preservation often
      has a high complication rate, pharyngocutaneous fistulas being the most common.
      These fistulas increase morbidity, prolong hospitalization, and potentially delay
      adjuvant treatment. Fistula rates in the literature range from 3% to 65%. Use of
      the pectoralis flap to prevent fistula formation has been adopted as a common
      practice at our institution. A review of our experience using the overlay
      myofascial showed a higher than desired complication rate. The aim of this study
      is to assess whether the use of integrated myocutaneous flap results in a lower
      fistula rate. STUDY DESIGN: A retrospective review of 30 patients followed by a
      pilot study of 10 patients. All underwent salvage laryngectomy after failed organ
      preservation. METHODS: The operation notes of 40 laryngectomy patients were
      analyzed. The patient/tumor characteristics, pretreatment, neck dissection, flap
      type, and fistula rate were documented. RESULTS: The patient sample was 25%
      female. All patients received prior radiotherapy, but only 37.5% received prior
      chemoradiation. Neck dissections were performed in 80% of these patients, 76% of
      the myocutaneous group, and 84% of the myofascial group. Advanced tumor stage was
      found in 42% of the myofascial group and 52% of the myocutaneous group. Five of
      the 19 myofascial patients developed a fistula, whereas seven of the 21
      myocutaneous patients developed a fistula. CONCLUSIONS: The use of the pectoralis
      myocutaneous flap (PMCF) in this pilot series did not show a lower rate of
      fistula; other alternatives should be pursued to decrease this complication.
      LEVEL OF EVIDENCE: 4.

PMID- 24122870
TI  - Advances in membrane emulsification. Part A: recent developments in processing
      aspects and microstructural design approaches.
AB  - Modern emulsion processing technology is strongly influenced by the market
      demands for products that are microstructure-driven and possess precisely
      controlled properties. Novel cost-effective processing techniques, such as
      membrane emulsification, have been explored and customised in the search for
      better control over the microstructure, and subsequently the quality of the final
      product. Part A of this review reports on the state of the art in membrane
      emulsification techniques, focusing on novel membrane materials and proof of
      concept experimental set-ups. Engineering advantages and limitations of a range
      of membrane techniques are critically discussed and linked to a variety of simple
      and complex structures (e.g. foams, particulates, liposomes etc.) produced
      specifically using those techniques.

PMID- 24122872
TI  - Using quantitative structure-activity relationship modeling to quantitatively
      predict the developmental toxicity of halogenated azole compounds.
AB  - Developmental toxicity is a relevant endpoint for the comprehensive assessment of
      human health risk from chemical exposure. However, animal developmental toxicity
      data remain unavailable for many environmental contaminants due to the complexity
      and cost of these types of analyses. Here we describe an approach that uses
      quantitative structure-activity relationship modeling as an alternative
      methodology to fill data gaps in the developmental toxicity profile of certain
      halogenated compounds. Chemical information was obtained and curated using the
      OECD Quantitative Structure-Activity Relationship Toolbox, version 3.0. Data from
      35 curated compounds were analyzed via linear regression to build the predictive
      model, which has an R(2) of 0.79 and a Q(2) of 0.77. The applicability domain
      (AD) was defined by chemical category and structural similarity. Seven
      halogenated chemicals that fit the AD but are not part of the training set were
      employed for external validation purposes. Our model predicted lowest observed
      adverse effect level values with a maximal threefold deviation from the observed
      experimental values for all chemicals that fit the AD. The good predictability of
      our model suggests that this method may be applicable to the analysis of
      qualifying compounds whenever developmental toxicity information is lacking or
      incomplete for risk assessment considerations.

PMID- 24122871
TI  - Netupitant PET imaging and ADME studies in humans.
AB  - Netupitant is a new, selective NK1 receptor antagonist under development for the
      prevention of chemotherapy-induced nausea and vomiting. Two studies were
      conducted to evaluate the brain receptor occupancy (RO) and disposition (ADME) of
      netupitant in humans. Positron emission tomography (PET) imaging with the NK1
      receptor-binding-selective tracer [(11) C]-GR205171 was used to evaluate the
      brain penetration of different doses of netupitant (100, 300, and 450 mg) and to
      determine the NK1 -RO duration. A NK1 -RO of 90% or higher was achieved with all
      doses in the majority of the tested brain regions at Cmax, with a long duration
      of RO. The netupitant minimal plasma concentration predicted to achieve a NK1 -RO
      of 90%, C90% , in the striatum was 225 ng/mL; after administration of netupitant
      300 mg, concentrations exceeded the C90% . In the ADME study, a single nominal
      dose of [(14) C]-netupitant 300 mg was used to assess its disposition. Absorption
      was rapid and netupitant was extensively metabolized via Phase I and II hepatic
      metabolism. Elimination of >90% was predicted at day 29 and was principally via
      hepatic/biliary route (>85%) with a minor contribution of the renal route (<5%).
      In conclusion, these studies demonstrate that netupitant is a potent agent
      targeting NK1 receptors with long lasting RO. In addition, netupitant is
      extensively metabolized and is mainly eliminated through the hepatic/biliary
      route and to a lesser extent via the kidneys. 

PMID- 24122873
TI  - Peroxisome proliferator-activated receptor alpha activates human multidrug
      resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription
      and increases rat biliary phosphatidylcholine secretion.
AB  - Multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4
      (MDR3/ABCB4) is a critical determinant of biliary phosphatidylcholine (PC)
      secretion. Clinically, mutations and partial deficiencies in MDR3 result in
      cholestatic liver injury. Thus, MDR3 is a potential therapeutic target for
      cholestatic liver disease. Fenofibrate is a peroxisome proliferator-activated
      receptor (PPAR) alpha ligand that has antiinflammatory actions and regulates bile
      acid detoxification. Here we examined the mechanism by which fenofibrate
      regulates MDR3 gene expression. Fenofibrate significantly up-regulated MDR3
      messenger RNA (mRNA) and protein expression in primary cultured human
      hepatocytes, and stimulated MDR3 promoter activity in HepG2 cells. In silico
      analysis of 5'-upstream region of human MDR3 gene revealed a number of PPARalpha
      response elements (PPRE). Electrophoretic mobility shift (EMSA) and chromatin
      immunoprecipitation (ChIP) assays demonstrated specific binding of PPARalpha to
      the human MDR3 promoter. Targeted mutagenesis of three novel PPREs reduced
      inducibility of the MDR3 promoter by fenofibrate. In collagen sandwich cultured
      rat hepatocytes, treatment with fenofibrate increased secretion of fluorescent PC
      into bile canaliculi. CONCLUSION: Fenofibrate transactivates MDR3 gene
      transcription by way of the binding of PPARalpha to three novel and functionally
      critical PPREs in the MDR3 promoter. Fenofibrate treatment further stimulates
      biliary phosphatidylcholine secretion in rat hepatocytes, thereby providing a
      functional correlate. We have established a molecular mechanism that may
      contribute to the beneficial use of fenofibrate therapy in human cholestatic
      liver disease.

PMID- 24122874
TI  - Interindividual variability in hepatic organic anion-transporting polypeptides
      and P-glycoprotein (ABCB1) protein expression: quantification by liquid
      chromatography tandem mass spectroscopy and influence of genotype, age, and sex.
AB  - Interindividual variability in protein expression of organic anion-transporting
      polypeptides (OATPs) OATP1B1, OATP1B3, OATP2B1, and multidrug resistance-linked P
      glycoprotein (P-gp) or ABCB1 was quantified in frozen human livers (n = 64) and
      cryopreserved human hepatocytes (n = 12) by a validated liquid chromatography
      tandem mass spectroscopy (LC-MS/MS) method. Membrane isolation, sample workup,
      and LC-MS/MS analyses were as described before by our laboratory. Briefly, total
      native membrane proteins, isolated from the liver tissue and cryopreserved
      hepatocytes, were trypsin digested and quantified by LC-MS/MS using signature
      peptide(s) unique to each transporter. The mean +/- S.D. (maximum/minimum range
      in parentheses) protein expression (fmol/ug of membrane protein) in human liver
      tissue was OATP1B1- 2.0 +/- 0.9 (7), OATP1B3- 1.1 +/- 0.5 (8), OATP2B1- 1 1.7 +/-
      0.6 (5), and P-gp- 0.4 +/- 0.2 (8). Transporter expression in the liver tissue
      was comparable to that in the cryopreserved hepatocytes. Most important is that
      livers with SLCO1B1 (encoding OATP1B1) haplotypes *14/*14 and *14/*1a [i.e.,
      representing single nucleotide polymorphisms (SNPs), c.388A > G, and c.463C > A]
      had significantly higher (P < 0.0001) protein expression than the reference
      haplotype (*1a/*1a). Based on these genotype-dependent protein expression data,
      we predicted (using Simcyp) an up to ~40% decrease in the mean area under the
      curve of rosuvastatin or repaglinide in subjects harboring these variant alleles
      compared with those harboring the reference alleles. SLCO1B3 (encoding OATP1B3)
      SNPs did not significantly affect protein expression. Age and sex were not
      associated with transporter protein expression. These data will facilitate the
      prediction of population-based human transporter-mediated drug disposition, drug
      drug interactions, and interindividual variability through physiologically based
      pharmacokinetic modeling. 

PMID- 24122875
TI  - Simultaneous quantification of methylene blue and its major metabolite, azure B,
      in plasma by LC-MS/MS and its application for a pharmacokinetic study.
AB  - A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed for the quantification of methylene blue (MB) and its major
      metabolite, azure B (AZB), in rat plasma. A simple protein precipitation using
      acetonitrile was followed by injection of the supernatant on to a Zorbax HILIC
      Plus column (3.5 um, 2.1 * 100 mm) with isocratic mobile phase consisting of 5 mM
      ammonium acetate in 10:90 (v/v) water:methanol at a flow rate of 0.3 mL/min and
      detection in positive ionization mode. The standard curve was linear over the
      concentration range from 1 to 1000 ng/mL for MB and AZB with coefficient of
      determination above 0.9930. The lower limit of quantification was 1 ng/mL using
      20 MUL of rat plasma sample. The intra- and inter-assay precision and accuracy
      were <12%. The developed analytical method was successfully applied to the
      pharmacokinetic study of MB and AZB in rats.

PMID- 24122877
TI  - Severe fetal ischaemic brain injury caused by homozygous protein C deficiency.

PMID- 24122876
TI  - ErbB2 activation upregulates glutaminase 1 expression which promotes breast
      cancer cell proliferation.
AB  - Active glutamine utilization is critical for tumor cell proliferation.
      Glutaminolysis represents the first and rate-limiting step of glutamine
      utilization and is catalyzed by glutaminase (GLS). Activation of ErbB2 is one of
      the major causes of breast cancers, the second most common cause of death for
      women in many countries. However, it remains unclear whether ErbB2 signaling
      affects glutaminase expression in breast cancer cells. In this study, we show
      that MCF10A-NeuT cell line has higher GLS1 expression at both mRNA and protein
      levels than its parental line MCF10A, and knockdown of ErbB2 decreases GLS1
      expression in MCF10A-NeuT cells. We further show that in these cells, ErbB2
      mediated upregulation of GLS1 is not correlated to c-Myc expression. Moreover,
      activation of neither PI3K-Akt nor MAPK pathway is sufficient to upregulate GLS1
      expression. Interestingly, inhibition of NF-kappaB blocks ErbB2-stimulated GLS1
      expression, whereas stimulation of NF-kappaB is sufficient to enhance GLS1 levels
      in MCF10A cells, suggesting a PI3K-Akt-independent activation of NF-kappaB
      upregulates GLS1 in ErbB2-positive breast cancer cells. Finally, knockdown or
      inhibition of GLS1 significantly decreased the proliferation of breast cancer
      cells with high GLS1 levels. Taken together, our data indicate that ErbB2
      activation promotes GLS1 expression via a PI3K-Akt-independent NF-kappaB pathway
      in breast cancer cells, identifying another oncogenic signaling pathway which
      stimulates GLS1 expression, and thus promoting glutamine utilization in cancer
      cells. These findings, if validated by in vivo model, may facilitate the
      identification of novel biochemical targets for cancer prevention and therapy.

PMID- 24122878
TI  - Monte Carlo simulations of proteins at constant pH with generalized Born solvent,
      flexible sidechains, and an effective dielectric boundary.
AB  - Titratable residues determine the acid/base behavior of proteins, strongly
      influencing their function; in addition, proton binding is a valuable reporter on
      electrostatic interactions. We describe a method for pK(a) calculations, using
      constant-pH Monte Carlo (MC) simulations to explore the space of sidechain
      conformations and protonation states, with an efficient and accurate generalized
      Born model (GB) for the solvent effects. To overcome the many-body dependency of
      the GB model, we use a "Native Environment" approximation, whose accuracy is
      shown to be good. It allows the precalculation and storage of interactions
      between all sidechain pairs, a strategy borrowed from computational protein
      design, which makes the MC simulations themselves very fast. The method is tested
      for 12 proteins and 167 titratable sidechains. It gives an rms error of 1.1 pH
      units, similar to the trivial "Null" model. The only adjustable parameter is the
      protein dielectric constant. The best accuracy is achieved for values between 4
      and 8, a range that is physically plausible for a protein interior. For
      sidechains with large pKa shifts, >=2, the rms error is 1.6, compared to 2.5 with
      the Null model and 1.5 with the empirical PROPKA method.

PMID- 24122879
TI  - On the accuracy of classifying hospitals on their performance measures.
AB  - The evaluation, comparison, and public report of health care provider performance
      is essential to improving the quality of health care. Hospitals, as one type of
      provider, are often classified into quality tiers (e.g., top or suboptimal) based
      on their performance data for various purposes. However, potential
      misclassification might lead to detrimental effects for both consumers and
      payers. Although such risk has been highlighted by applied health services
      researchers, a systematic investigation of statistical approaches has been
      lacking. We assess and compare the expected accuracy of several commonly used
      classification methods: unadjusted hospital-level averages, shrinkage estimators
      under a random-effects model accommodating between-hospital variation, and two
      others based on posterior probabilities. Assuming that performance data follow a
      classic one-way random-effects model with unequal sample size per hospital, we
      derive accuracy formulae for these classification approaches and gain insight
      into how the misclassification might be affected by various factors such as
      reliability of the data, hospital-level sample size distribution, and cutoff
      values between quality tiers. The case of binary performance data is also
      explored using Monte Carlo simulation strategies. We apply the methods to real
      data and discuss the practical implications.

PMID- 24122880
TI  - Differences between easy- and difficult-to-mill chickpea (Cicer arietinum L.)
      genotypes. Part III: free sugar and non-starch polysaccharide composition.
AB  - BACKGROUND: Parts I and II of this series of papers identified several
      associations between the ease of milling and the chemical compositions of
      different chickpea seed fractions. Non-starch polysaccharides were implicated;
      hence, this study examines the free sugars and sugar residues. RESULTS: Difficult
      milling is associated with: (1) lower glucose and xylose residues (less cellulose
      and xyloglucans) and more arabinose, rhamnose and uronic acid in the seed coat,
      suggesting a more flexible seed coat that resists cracking and decortication; (2)
      a higher content of soluble and insoluble non-starch polysaccharide fractions in
      the cotyledon periphery, supporting a pectic polysaccharide mechanism comprising
      arabinogalacturonan, homogalacturonan, rhamnogalalcturonan, and glucuronan
      backbone structures; (3) higher glucose and mannose residues in the cotyledon
      periphery, supporting a lectin-mediated mechanism of adhesion; and (4) higher
      arabinose and glucose residues in the cotyledon periphery, supporting a mechanism
      involving arabinogalactan-proteins. CONCLUSION: This series has shown that the
      chemical composition of chickpea does vary in ways that are consistent with
      physical explanations of how seed structure and properties relate to milling
      behaviour. Seed coat strength and flexibility, pectic polysaccharide binding,
      lectins and arabinogalactan-proteins have been implicated. Increased
      understanding in these mechanisms will allow breeding programmes to optimise
      milling performance in new cultivars.

PMID- 24122881
TI  - Metabolomic analysis of soil communities can be used for pollution assessment.
AB  - Metabolic profiling can be used to assess the changes in biochemical profiles of
      soil communities living in contaminated sites. The term "community metabolomics"
      is proposed for the application of metabolomics techniques to the study of the
      entire community of a soil sample. The authors anticipate the present study to be
      a starting point for the use of this technique to assess how communities respond
      to factors such as pollution and climate change.

PMID- 24122882
TI  - PNPLA3, the history of an orphan gene of the potato tuber protein family that
      found an organ: the liver.

PMID- 24122883
TI  - Pharmacokinetic and pharmacodynamic properties of canakinumab in patients with
      gouty arthritis.
AB  - Pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1beta
      monoclonal antibody, canakinumab, in gouty arthritis patients from three studies
      are reported. Canakinumab has low serum clearance (0.214 L/day), low steady-state
      volume of distribution (7.44 L), a 25.8-day half-life, and approximately 60%
      subcutaneous absolute bioavailability in a typical 93-kg patient. Creatinine
      clearance had a small positive impact on serum canakinumab clearance that is not
      likely to be clinically relevant. Binding to circulating IL-1beta was
      demonstrated by increases in total serum IL-1beta following canakinumab dosing.
      Total IL-1beta kinetics and canakinumab pharmacokinetics were characterized by a
      population-based pharmacokinetic-binding model, where the estimated apparent in
      vivo dissociation constant (signifying binding affinity of canakinumab to
      circulating IL-1beta) was 0.99 nmol/L in gouty arthritis patients. Canakinumab
      treatment provided rapid, sustained decreases in C-reactive protein and serum
      amyloid A, provided superior pain relief to triamcinolone acetonide, and
      increased time to first recurrent attack (P <= 0.01 favoring all canakinumab
      doses vs. triamcinolone acetonide). 

PMID- 24122884
TI  - Precision criteria to derive sample size when designing pediatric pharmacokinetic
      studies: which measure of variability should be used?
AB  - A new approach for calculation of sample size in pediatric clinical
      pharmacokinetic studies was suggested based on desired precision for a
      pharmacokinetic parameter of interest. The estimate of variability for sample
      size calculations could be obtained from different sources. It is not known
      whether these sources constantly show higher/lower variability across compounds
      and age groups. We obtained estimates of variability for clearance, volume of
      distribution and area under the plasma concentration-time curve for 5 drugs from
      adult/pediatric classic clinical pharmacokinetic studies, and physiologically
      based pharmacokinetics (PBPK) combined with in vitro-in vivo extrapolation.
      Estimates were applied to the proposal methodology for non-compartmental
      analysis. Sample size was different for each drug based on various estimates of
      variability from different pharmacokinetic parameters and depending on the age.
      Overall, there was no consistent discrepancy in sample size calculated according
      to the source of variability. A conservative approach should be taken when using
      "precision based methodology" knowing that various sources of initial estimates
      of variability will not lead to similar sample size calculations. Although PBPK
      simulations could be used for estimating variability, further work is required to
      investigate the best approach to estimate variability of pharmacokinetic
      parameters in pediatric populations and hence sample size calculations. 

PMID- 24122885
TI  - Chrysin inhibits metastatic potential of human triple-negative breast cancer
      cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal
      transition, and PI3K/Akt signaling pathway.
AB  - Chrysin, a naturally occurring flavone, has been shown to inhibit cell
      proliferation and induce cell apoptosis in various cancers. However, the effect
      and mechanisms of chrysin on cancer metastasis are still enigmatic. In this
      study, metastatic triple-negative breast cancer (TNBC) cell lines were used to
      evaluate the antimetastatic activity of chrysin. The results showed that chrysin
      (5, 10 and 20 MUM) significantly suppressed TNBC cell migration and invasion in a
      dose-dependent manner. Human matrix metalloproteinase (MMP) antibody array
      demonstrated that MMP-10 was downregulated by chrysin, which was further verified
      by Western blotting and ELISA. Moreover, it was shown that chrysin induced
      increased E-cadherin expression and decreased expression of vimentin, snail and
      slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial
      mesenchymal transition. More importantly, it was demonstrated that inhibiting the
      Akt signal pathway might play a central role in chrysin-induced antimetastatic
      activity by regulating MMP-10 and epithelial-mesenchymal transition. In
      conclusion, our study indicates that chrysin exerts antimetastatic activities in
      TNBC cells, which suggests that chrysin might be a potential therapeutic
      candidate for the treatment of advanced or metastatic breast cancer.

PMID- 24122886
TI  - Long term outcome of Ph+ CML patients achieving complete cytogenetic remission
      with interferon based therapy moving from interferon to imatinib era.
AB  - Interferon alpha (IFNalpha) prolongs survival of CML patients achieving CCyR and
      potentially synergizes with TKIs. We report on the molecular status and long term
      outcome of 121 patients who were treated in Italy between 1986 and 2000 with
      IFNalpha based therapy and who obtained CCyR. After a median follow up of 16.5
      years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the
      CCyR on IFNalpha, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to
      imatinib when they were still in CCyR on IFNalpha, and all 26 are alive and in
      CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%)
      continued and 23 (49%) discontinued IFNalpha, respectively, and 39/47 (83%) are
      alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available
      in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01%
      (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient
      was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20
      years is 92 and 84%, respectively. This study confirms that CCyR achieved with
      IFNalpha and maintained with or without imatinib or any other therapy
      significantly correlates with long term survival in CML patients who mostly have
      MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be
      unnecessary for such a long survival. This study further supports development of
      studies testing the clinical effect of the combinations of TKIs with IFNalpha.

PMID- 24122887
TI  - Dab2, megalin, cubilin and amnionless receptor complex might mediate intestinal
      endocytosis in the suckling rat.
AB  - We previously proposed that Dab2 participates in the endocytosis of milk
      macromolecules in rat small intestine. Here we investigate the receptors that may
      mediate this endocytosis by studying the effects of age and diet on megalin,
      VLDLR, and ApoER2 expression, and that of age on the expression of cubilin and
      amnionless. Of megalin, VLDLR and ApoER2, only the megalin expression pattern
      resembles that of Dab2 previously reported. Thus the mRNA and protein levels of
      megalin and Dab2 are high in the intestine of the suckling rat, down-regulated by
      age and up-regulated by milk diet, mainly in the ileum. Neither age nor diet
      affect ApoER2 mRNA levels. The effect of age on VLDLR mRNA levels depends on the
      epithelial cell tested but they are down-regulated by milk diet. In the suckling
      rat, the intestinal expressions of both cubilin and amnionless are similar to
      that of megalin and megalin, cubilin, amnionless and Dab2 co-localize at the
      microvilli and in the apical endocytic apparatus. Co-localization of Dab2 with
      ApoER2 and VLDLR at the microvilli and in the apical endocytic apparatus is also
      observed. This is the first report showing intestinal co-localization of:
      megalin/cubilin/amnionless/Dab2, VLDLR/Dab2 and ApoER2/Dab2. We conclude that the
      megalin/cubilin/amnionless/Dab2 complex/es participate in intestinal processes,
      mainly during the lactation period and that Dab2 may act as an adaptor in
      intestinal processes mediated by ApoER2 and VLDLR.

PMID- 24122888
TI  - Hepatitis C genotype 1 virus with low viral load and rapid virologic response to
      peginterferon/ribavirin obviates a protease inhibitor.

PMID- 24122890
TI  - Significance of aortic valve calcification in patients with low-gradient low-flow
      aortic stenosis.
AB  - BACKGROUND: Assessment of patients with aortic stenosis (AS) and impaired left
      ventricular function remains challenging. Aortic valve calcium (AVC) scoring with
      computed tomography (CT) and fluoroscopy has been proposed as means of diagnosing
      and predicting outcomes in patients with severe AS. HYPOTHESIS: Severity of
      aortic valve calcification correlates with the diagnosis of true severe AS and
      outcomes in patients with low-gradient low-flow AS. METHODS: Echocardiography and
      CT database records from January 1, 2000 to September 26, 2009 were reviewed.
      Patients with aortic valve area (AVA)<1.0 cm2 who had ejection fraction (EF)<=25%
      and mean valvular gradient<=25 mmHg with concurrent noncontrast CT scans were
      included. AVC was evaluated using CT and fluoroscopy. Mortality and aortic valve
      replacement (AVR) were established using the Social Security Death Index and
      medical records. The role of surgery in outcomes was evaluated. RESULTS: Fifty
      one patients who met the above criteria were included. Mean age was 75.1+/-9.6
      years, and 15 patients were female. Mean EF was 21%+/-4.6% with AVA of 0.7+/-0.1
      cm2. The peak and mean gradients were 35.5+/-10.6 and 19.0+/-5.1 mmHg,
      respectively. Median aortic valve calcium score was 2027 Agatston units. Mean
      follow-up was 908 days. Patients with calcium scores above the median value were
      found to have increased mortality (P=0.02). The benefit of surgery on survival
      was more pronounced in patients with higher valvular scores (P=0.001).
      Fluoroscopy scoring led to similar findings, where increased AVC predicted worse
      outcomes (P=0.04). CONCLUSIONS: In patients with low-gradient low-flow AS, higher
      valvular calcium score predicts worse long-term mortality. AVR is associated with
      improved survival in patients with higher valve scores.

PMID- 24122891
TI  - Prenatal diagnosis of exophytic nevus sebaceous of the scalp.
AB  - Nevus sebaceous is a complex hamartoma most commonly found on the scalp, face,
      and neck and is often present at birth, although some may be diagnosed later in
      infancy. We report the first prenatal diagnosis of isolated nevus sebaceous that
      presented at 19 weeks' gestation as a large and exophytic tumor of the scalp.
      This case emphasizes the crucial role of ultrasound examination performed with
      high-frequency probes, which revealed associated diffuse lesions of the face.
      Identification of such a facial involvement could have a dramatic prognostic
      impact.

PMID- 24122893
TI  - Studies on excretion kinetics of ten constituents in rat urine after oral
      administration of Shensong Yangxin Capsule by UPLC-MS/MS.
AB  - A rapid and sensitive ultra-high performance liquid chromatography-mass
      spectrometry (UPLC-MS/MS) method was developed and validated for the
      quantification of 10 major active constituents in rat urine after oral
      administration of Shensong Yangxin Capsule (SSYX) using diazepam as an internal
      standard (IS). The urine samples were pretreated and extracted by solid-phase
      extraction prior to UPLC. Chromatographic separation was achieved on a Waters C18
      (2.1 * 50 mm, 1.7 um) column using a gradient elution program with 0.1% formic
      acid aqueous solution and acetonitrile at a flow rate of 0.4 mL/min. Detection
      and quantitation were accomplished by a hybrid quadrupole mass spectrometer using
      electrospray ionization source and multiple reaction monitoring in the positive
      ionization mode. The mass transition ion-pairs (m/z) for quantitation were all
      optimized and the total run time was 4.50 min. The specificity, linearity,
      accuracy, precision, recovery, matrix effect and stabilities were all validated
      for the analytes in urine samples. The validation results indicated that this
      method was simple, rapid, specific and reliable. The proposed method was
      successfully applied to investigate the urinary excretion kinetics of 10
      compounds in rat after oral administration of SSYX.

PMID- 24122894
TI  - The RTAM electronic bibliography, version 17.0, on relativistic theory of atoms
      and molecules.
AB  - The RTAM bibliography is freely available at rtam.csc.fi and the Version 17.0 of
      August 22, 2013 now contains 16,566 items from the year 1916-2013. "Production
      works" were systematically covered until 1999. Since the year 2000, mainly
      methodological papers were included. The methods and principles behind RTAM are
      described.

PMID- 24122892
TI  - Glial localization of antiquitin: implications for pyridoxine-dependent epilepsy.
AB  - OBJECTIVE: A high incidence of structural brain abnormalities has been reported
      in individuals with pyridoxine-dependent epilepsy (PDE). PDE is caused by
      mutations in ALDH7A1, also known as antiquitin. How antiquitin dysfunction leads
      to cerebral dysgenesis is unknown. In this study, we analyzed tissue from a child
      with PDE as well as control human and murine brain to determine the normal
      distribution of antiquitin, its distribution in PDE, and associated brain
      malformations. METHODS: Formalin-fixed human brain sections were subjected to
      histopathology and fluorescence immunohistochemistry studies. Frozen brain tissue
      was utilized for measurement of PDE-associated metabolites and Western blot
      analysis. Comparative studies of antiquitin distribution were performed in
      developing mouse brain sections. RESULTS: Histologic analysis of PDE cortex
      revealed areas of abnormal radial neuronal organization consistent with type Ia
      focal cortical dysplasia. Heterotopic neurons were identified in subcortical
      white matter, as was cortical astrogliosis, hippocampal sclerosis, and status
      marmoratus of the basal ganglia. Highly elevated levels of lysine metabolites
      were present in postmortem PDE cortex. In control human and developing mouse
      brain, antiquitin immunofluorescence was identified in radial glia, mature
      astrocytes, ependyma, and choroid plexus epithelium, but not in neurons. In PDE
      cortex, antiquitin immunofluorescence was greatly attenuated with evidence of
      perinuclear accumulation in astrocytes. INTERPRETATION: Antiquitin is expressed
      within glial cells in the brain, and its dysfunction in PDE is associated with
      neuronal migration abnormalities and other structural brain defects. These
      malformations persist despite postnatal pyridoxine supplementation and likely
      contribute to neurodevelopmental impairments.

PMID- 24122895
TI  - High prevalence of HHV8 infection and specific killer cell immunoglobulin-like
      receptors allotypes in Sardinian patients with type 2 diabetes mellitus.
AB  - The development of type 2 diabetes is thought to involve both environmental,
      possibly infectious, and genetic factors. Recently, a high prevalence of human
      herpesvirus 8 (HHV8) infection was observed in type 2 diabetes patients, and
      specific killer cell immunoglobulin-like receptors (KIR) allotypes were
      associated to both increased susceptibility to herpesvirus infection and risk to
      develop diabetes. However, no clear gene-disease or virus-disease associations
      have been established. To investigate the possible interplay between HHV8
      infection, KIR allotype and type 2 diabetes, virus prevalence and KIR genotype
      were analyzed by PCR in 168 patients affected by type 2 diabetes and 108 control
      individuals belonging to the Sardinian population. Results showed a significant
      increase of HHV8 prevalence in type 2 diabetes patients versus controls (57% vs.
      17%, P < 0.001), and a significant increase of KIR2DL2/DS2 homozygosity in
      diabetes patients infected with HHV8 compared to uninfected ones (64% vs. 14%, P
      < 0.0001), resulting in a significant OR of 11.31. In addition, the analysis of
      the frequency of the KIR2DL2/DS2 receptor and its HLA-C1 ligand, accordingly to
      the status of HHV8 infection, showed a significant increased correlation between
      KIR2DL2/DS2, type 2 diabetes and HLA-C1C1 genotype in the type 2 diabetes
      patients infected with HHV8 compared to uninfected ones (62% vs. 15%, P < 0.0001,
      OR = 8.64). These findings provide preliminary evidence that HHV8 infection might
      be a cofactor for type 2 diabetes in a specific subset of genetically susceptible
      individuals, and suggest the possibility that such patients might have an
      impaired immune-mediated component contributing to the development of type 2
      diabetes.

PMID- 24122896
TI  - Fungal alternative splicing is associated with multicellular complexity and
      virulence: a genome-wide multi-species study.
AB  - Alternative splicing (AS) is a cellular process that increases a cell's coding
      capacity from a limited set of genes. Although AS is common in higher plants and
      animals, its prevalence in other eukaryotes is mostly unknown. In fungi the
      involvement of AS in gene expression and its effect on multi-cellularity and
      virulence is of great medical and economic interest. We present a genome-wide
      comparative study of AS in 23 informative fungi of different taxa, based on
      alignments of public transcript sequences. Random sampling of expressed sequence
      tags allows for robust and comparable estimations of AS rates. We find that a
      greater fraction of fungal genes than previously expected is associated with AS.
      We estimate that on average, 6.4% of the annotated genes are affected by AS, with
      Cryptococcus neoformans showing an extraordinary rate of 18%. The investigated
      Basidiomycota show higher average AS rates (8.6%) than the Ascomycota (6.0%),
      although not significant. We find that multi-cellular complexity and younger
      evolutionary age associate with higher AS rates. Furthermore, AS affects genes
      involved in pathogenic lifestyle, particularly in functions of stress response
      and dimorphic switching. Together, our analysis strongly supports the view that
      AS is a rather common phenomenon in fungi and associates with higher multi
      cellular complexity. 

PMID- 24122897
TI  - Oromandibular dystonia: long-term management with botulinum toxin.
AB  - OBJECTIVES/HYPOTHESIS: To review the long-term management of patients with
      oromandibular dystonia (OMD) treated using botulinum toxin. STUDY DESIGN:
      Retrospective chart review at a clinical research center. METHODS: Between 1995
      and 2011, 59 patients with a diagnosis of OMD were treated with botulinum toxin.
      Data were collected on patient demographics, disease characteristics, and long
      term treatment outcomes. Differences in management between an earlier published
      series of the first 20 OMD patients treated with botulinum toxin at this center
      and subsequent patients were analyzed. RESULTS: Patients were more commonly
      female (72% vs. 28%) with an average age at first botulinum treatment of 56.6
      years. The median number of treatments was five (range, 1-35 treatments). Average
      time between treatments was 3.8 months (+/- 5.2). Overall, 47.5%, had the jaw
      closing form of OMD, which was associated with a preferential deviation to one
      side in 53.6%. These patients received initial injections to the masseter +/-
      temporalis muscle; the external pterygoid was injected for associated lateral jaw
      deviation. Internal pterygoid injections were rarely used (3.4%). For the jaw
      opening form, injections were initially administered to the external pterygoid,
      with the addition of anterior digastric for ongoing symptoms. When compared with
      patients in the older series, more patients since 1988 had treatments to the
      external pterygoid (P = .001) and anterior digastric (P = .006) in accordance
      with an increase in the diagnosis of jaw-opening OMD (P = .05). CONCLUSIONS: Long
      term management of OMD with botulinum toxin has minimal morbidity and is useful
      for all clinical forms. Injections can be titrated by dose and location to
      address the predominant muscle groups involved.

PMID- 24122898
TI  - The hunt for treatment options of fatty liver continues: effects of retinoic acid
      on hepatic steatosis reveal novel transcriptional interactions of nuclear
      receptors.

PMID- 24122899
TI  - Integrated testing and assessment approaches for skin sensitization: a
      commentary.
AB  - A Bayesian integrated testing strategy (ITS) approach, aiming to assess skin
      sensitization potency, has been presented, in which data from various types of in
      vitro assays are integrated and assessed in combination for their ability to
      predict in vivo skin sensitization data. Here we discuss this approach and
      compare it to our quantitative mechanistic modeling (QMM) approach based on
      physical organic chemistry. The main findings of the Bayesian study are
      consistent with our chemistry-based approach and our previously published
      assessment of the key determinants of sensitization potency, in particular the
      relatively high predictive value found for chemical reactivity data and the
      relatively low predictive value for bioavailability parameters. As it stands at
      present the Bayesian approach does not utilize the full range of predictive
      capability that is already available, and aims only to assign potency categories
      rather than numerical potency values per se. In contrast, for many chemicals the
      QMM approach can already provide numerical potency predictions. However, the
      Bayesian approach may have potential for those chemicals where a chemistry
      modeling approach cannot provide a complete answer (e.g. pro-electrophiles whose
      in cutaneo activation cannot currently be modeled confidently). Nonetheless, our
      main message is of the importance of leveraging chemistry insights and read
      across approaches to the fullest extent possible.

PMID- 24122900
TI  - Does long-term entecavir treatment really reduce hepatocellular carcinoma
      incidence in patients with hepatitis B virus infection?

PMID- 24122902
TI  - Increasing platelet concentration in platelet-rich plasma inhibits anterior
      cruciate ligament cell function in three-dimensional culture.
AB  - Tissue engineering is one new strategy being developed to treat ACL ruptures. One
      such approach is bio-enhanced ACL repair, where a suture repair is supplemented
      with a bio-active scaffold containing platelets. However, the optimal
      concentration of platelets to stimulate ACL healing is not known. We hypothesized
      that increasing platelet concentrations in the scaffold would enhance critical
      cell behaviors. Porcine ACL fibroblasts were obtained from explant culture and
      suspended in platelet poor plasma (PPP), 1* platelet-rich plasma (PRP), 3* PRP,
      5* PRP, or phosphate buffered saline (PBS). The cell suspensions were cultured in
      a 3D collagen scaffold. Cellular metabolism (MTT assay), apoptosis (TUNEL assay),
      and gene expression for type I and type III collagen were measured. 1* PRP
      significantly outperformed 5* PRP in all parameters studied: Type I and III
      collagen gene expression, apoptosis prevention, and cell metabolism stimulation.
      ACL fibroblasts cultured with 1* PRP had the highest type I and type III collagen
      gene expression. 1* PRP and PPP groups had the highest cell metabolism and lowest
      apoptosis rates. Concentration of platelets had significant effects on the
      behavior of ACL fibroblasts; thus, it is an important parameter that should be
      specified in clinical or basic science studies.

PMID- 24122901
TI  - Effect of race on outcomes after allogeneic hematopoietic cell transplantation
      for severe aplastic anemia.
AB  - We compared outcomes after hematopoietic cell transplantation in patients of
      African American (n = 84) and Caucasian (n = 215) descent with severe aplastic
      anemia. African Americans and Caucasians were matched for age, donor-recipient
      human leukocyte antigen match, graft type, and transplantation year. The median
      follow-up of surviving patients was 5 years. In multivariate analysis, overall
      mortality risks were higher for African Americans compared to Caucasians
      (relative risk 1.73, P = 0.01). The 5-year probabilities of overall survival
      adjusted for interval from diagnosis to transplantation, and performance score
      was 58% for African Americans and 73% for Caucasians. The day-100 cumulative
      incidence of grade III-IV, but not grade II-IV acute graft-versus-host disease
      (GVHD), was higher in African Americans compared to Caucasians (29% vs. 13%, P =
      0.006). Although the 5-year cumulative incidence of chronic GVHD was not
      significantly different between the racial groups, African Americans were more
      likely to have extensive chronic GVHD compared to Caucasians (72% vs. 49%, P =
      0.06). Survival differences between Caucasians and African Americans can be
      attributed to multiple factors. Our data suggest that some of the observed
      survival differences between Caucasians and African Americans may be explained by
      higher rates of acute GVHD and severity of chronic GVHD.

PMID- 24122903
TI  - External laryngotracheal trauma: Incidence, airway control, and outcomes in a
      large Canadian center.
AB  - OBJECTIVES/HYPOTHESIS: Laryngotracheal trauma encompasses a subset of relatively
      uncommon yet life-threatening injuries requiring prompt intervention to prevent
      short- and long-term aerodigestive tract sequelae. Minimal literature exists
      regarding laryngotracheal injuries on a population level, particularly among
      Canadian centers. STUDY DESIGN: Case series. METHODS: Regional health databases
      containing in-patient admissions, emergency department visits, and trauma service
      activations using International Classification of Diseases (ICD) diagnostic codes
      were queried to identify all laryngotracheal injuries diagnosed from April 1,
      1995, to December 31, 2011. Health records and diagnostic imaging were evaluated
      for mechanism, injuries, airway management, and long-term aerodigestive function.
      RESULTS: Eighty-nine patients met inclusion criteria, equating to 1/1042
      admissions and 1/2478 emergency presentations. Nineteen percent of injuries were
      severe (Schaefer-Fuhrman score >= 4). Airway intervention was performed at
      presentation in 65% of patients, with 13.5% necessitating emergent surgical
      airway; 52% underwent investigative or interventional airway surgery. Nine
      patients (16%) had long-term moderate or severe dysphonia; 14.5% had dysphagia.
      Odds ratio for death and long-term dysphonia among severe compared to minor
      laryngotracheal injuries were 7.1 (95% CI = 1.4-35.4) and 17.2 (95% CI = 3.3
      91.1), respectively. Several factors were identified that predicted airway
      management and outcomes. CONCLUSION: Traumatic laryngotracheal injuries are more
      common than previously reported, due to increased recognition. Many can be
      managed nonoperatively; however, cases require individual evaluation with
      judicious airway management and intervention to minimize aerodigestive sequelae.
      Severe injuries are associated with death and dysphonia but not with dysphagia.
      LEVEL OF EVIDENCE: 4.

PMID- 24122904
TI  - Potential contribution of saliva to the sexual transmission of HIV through the
      secretion of CCL20 by genital epithelial cells.
AB  - Saliva can be considered as an important actor during sexual intercourse.
      However, there is no data concerning its influence on HIV sexual transmission.
      The aim of this study was to evaluate the role of whole saliva on the in vitro
      secretion of CCL20 by monolayered HEC-1A endocervical epithelium cells. HEC-1A
      cells were cultivated in 96-well microplates and incubated with specimens of
      whole saliva collected from 57 subjects tested seropositive (n = 34) or
      seronegative (n = 23) for HIV and presenting different oral conditions (healthy
      periodontally, n = 22, and gingivitis/periodontitis, n = 35). The production of
      CCL20 in the supernatants of HEC-1A cells after overnight incubation at 37
      degrees C was quantified using ELISA. The salivary concentration of lactoferrin
      (Lf) and IL-1beta was tested by ELISA. Saliva samples were found able to
      stimulate dramatically the production of CCL20 by epithelial cells, increasing
      this synthesis by a mean factor of 38.1 with reference to untreated cells. This
      stimulation was equivalent to that observed with IL-1beta used as positive
      control. Although no difference was observed according to oral condition, HIV
      status or salivary concentration of Lf and IL-1beta, the high salivary
      concentration of the latter protein could acknowledge in large part for the
      overproduction of CCL20 by HEC-1A cells when stimulated by saliva. Saliva was
      shown to significantly increase CCL20 secretion and may be responsible for an
      enhanced recruitment of dendritic/Langerhans cells at the genital level. These
      results suggest that saliva could facilitate HIV entry and possibly other
      pathogens through the genital mucosa during heterosexual intercourse.

PMID- 24122905
TI  - Viral infection and focal cortical dysplasia. Reply.

PMID- 24122906
TI  - Identifiability of subgroup causal effects in randomized experiments with
      nonignorable missing covariates.
AB  - Although randomized experiments are widely regarded as the gold standard for
      estimating causal effects, missing data of the pretreatment covariates makes it
      challenging to estimate the subgroup causal effects. When the missing data
      mechanism of the covariates is nonignorable, the parameters of interest are
      generally not pointly identifiable, and we can only get bounds for the parameters
      of interest, which may be too wide for practical use. In some real cases, we have
      prior knowledge that some restrictions may be plausible. We show the
      identifiability of the causal effects and joint distributions for four
      interpretable missing data mechanisms and evaluate the performance of the
      statistical inference via simulation studies. One application of our methods to a
      real data set from a randomized clinical trial shows that one of the nonignorable
      missing data mechanisms fits better than the ignorable missing data mechanism,
      and the results conform to the study's original expert opinions. We also
      illustrate the potential applications of our methods to observational studies
      using a data set from a job-training program.

PMID- 24122907
TI  - Strategy for managing maternal variant RHD alleles in Rhesus D negative obstetric
      populations during fetal RHD genotyping.
AB  - OBJECTIVES: Fetal RHD screening programs that aim to reduce unnecessary antenatal
      anti-D prophylaxis are being introduced into clinical practice. Strategies to
      manage women serologically typed as Rhesus D negative who have maternal RHD
      variants are needed. This study describes maternal RHD allelic variants detected
      in nonselected and alloimmunised Rhesus D negative obstetric populations and
      explores a mathematical approach to identify these variants. METHODS: Fetal RHD
      status was defined by testing cell-free fetal DNA in maternal plasma. Women at
      risk of an RHD variant were identified by selection for C and E haplotypes or by
      recognition of low polymerase chain reaction cycle threshold on fetal RHD typing.
      Maternal RHD alleles were defined by SNP profiling or sequencing. RESULTS: The
      prevalence of RHD variants in nonselected and alloimmunised groups was 1% (6/603)
      and 5.5% (6/110), respectively (p < 0.001). An inverse association between RHD
      cycle threshold values and gestational age was described by a linear model (p <
      0.001). Standard residual values with a Z score threshold of -3.00 would have
      detected all maternal variants with one (1/713) false positive. CONCLUSIONS: The
      prevalence of maternal RHD variants was significantly higher in alloimmunised
      cases. The causative mechanism for this needs further investigation. Mathematical
      modeling simplifies the detection of maternal RHD variants.

PMID- 24122908
TI  - First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in
      healthy volunteers.
AB  - TRV130 is a G protein-biased ligand at the u-opioid receptor. In preclinical
      studies it was potently analgesic while causing less respiratory depression and
      gastrointestinal dysfunction than morphine, suggesting unique benefits in acute
      pain management. A first-in-human study was conducted with ascending doses of
      TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in
      healthy volunteers. TRV130 was well-tolerated over the dose range 0.15 to 7 mg
      administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax
      were dose-linear, with AUC0-inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to
      102.36 ng/mL across the dose range tested, with half-life of 1.6-2.7 hours. A 1.5
      mg dose of TRV130 was also well-tolerated when administered as 30, 15, 5, and 1
      minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6
      phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused
      dose- and exposure-related pupil constriction, confirming central compartment u
      opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7
      mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose
      escalation. These findings suggest that TRV130 may have a broad margin between
      doses causing u-opioid receptor-mediated pharmacology and doses causing u-opioid
      receptor-mediated intolerance. 

PMID- 24122910
TI  - Accurate density functional theory description of binding constants and NMR
      chemical shifts of weakly interacting complexes of C60 with corannulene-based
      molecular bowls.
AB  - Density functional calculations on "catch and release" complexes of C60 with
      corannulene derived molecular bowls show that computationally obtained (1) H
      nuclear magnetic resonance (NMR) chemical shifts can be used as a reliable
      predictor of binding constants. A wide range of functionals was benchmarked
      against accurate ab initio calculations to ensure a credible representation of
      the weak forces that dominate the interactions in these systems. The most
      reliable density functional theory (DFT) results were then calibrated using
      experimentally observed NMR data. Careful analysis and comparison of a wide range
      of commonly used density functionals shows that the explicit inclusion of
      dispersion corrections is currently the only reliable way to accurately describe
      the systems investigated in our study. Moreover, we are able to show that the B97
      D and omegaB97X-D functionals are not only able to reproduce ab initio benchmark
      calculations, but they do so accurately with a moderately sized basis sets and
      without the problems of numerical integration we encountered with other
      functionals in this study.

PMID- 24122909
TI  - Translation regulation and proteasome mediated degradation cooperate to keep stem
      loop binding protein low in G1-phase.
AB  - Histone mRNA levels are cell cycle regulated, and the major regulatory steps are
      at the posttranscriptional level. A major regulatory mechanism is S-phase
      restriction of Stem-loop binding protein (SLBP) which binds to the 3' end of
      histone mRNA and participates in multiple steps of histone mRNA metabolism,
      including 3' end processing, translation and regulation of mRNA stability. SLBP
      expression is cell cycle regulated without significant change in its mRNA level.
      SLBP expression is low in G1 until just before S phase where it functions and at
      the end of S phase SLBP is degraded by proteasome complex depending on
      phosphorylations on Thr60 and Thr61. Here using synchronized HeLa cells we showed
      that SLBP production rate is low in early G1 and recovers back to S phase level
      somewhere between early and mid-G1. Further, we showed that SLBP is unstable in
      G1 due to proteasome mediated degradation as a novel mechanism to keep SLBP low
      in G1. Finally, the S/G2 stable mutant form of SLBP is degraded by proteasome in
      G1, indicating that indicating that the SLBP degradation in G1 is independent of
      the previously identified SLBP degradation at S/G2. In conclusion, as a mechanism
      to limit histone production to S phase, SLBP is kept low in G1 phase due to
      cooperative action of translation regulation and proteasome mediated degradation
      which is independent of previously known S/G2 degradation.

PMID- 24122911
TI  - The use of propensity score methods with survival or time-to-event outcomes:
      reporting measures of effect similar to those used in randomized experiments.
AB  - Propensity score methods are increasingly being used to estimate causal treatment
      effects in observational studies. In medical and epidemiological studies,
      outcomes are frequently time-to-event in nature. Propensity-score methods are
      often applied incorrectly when estimating the effect of treatment on time-to
      event outcomes. This article describes how two different propensity score methods
      (matching and inverse probability of treatment weighting) can be used to estimate
      the measures of effect that are frequently reported in randomized controlled
      trials: (i) marginal survival curves, which describe survival in the population
      if all subjects were treated or if all subjects were untreated; and (ii) marginal
      hazard ratios. The use of these propensity score methods allows one to replicate
      the measures of effect that are commonly reported in randomized controlled trials
      with time-to-event outcomes: both absolute and relative reductions in the
      probability of an event occurring can be determined. We also provide guidance on
      variable selection for the propensity score model, highlight methods for
      assessing the balance of baseline covariates between treated and untreated
      subjects, and describe the implementation of a sensitivity analysis to assess the
      effect of unmeasured confounding variables on the estimated treatment effect when
      outcomes are time-to-event in nature. The methods in the paper are illustrated by
      estimating the effect of discharge statin prescribing on the risk of death in a
      sample of patients hospitalized with acute myocardial infarction. In this
      tutorial article, we describe and illustrate all the steps necessary to conduct a
      comprehensive analysis of the effect of treatment on time-to-event outcomes.

PMID- 24122912
TI  - Simultaneous determination of three major lignans in rat plasma by LC-MS/MS and
      its application to a pharmacokinetic study after oral administration of
      Diphylleia sinensis extract.
AB  - A sensitive and selective liquid chromatography tandem mass spectrometry was
      developed and validated for the simultaneous determination of three major lignans
      (podophyllotoxin, epipodophyllotoxin, and 4'-demethylpodophyllotoxin) in rat
      plasma using diphenhydramine as the internal standard. The analytes were detected
      using a triple quadrupole mass spectrometer that was equipped with an
      electrospray ionization source in the positive ion and selected reaction
      monitoring modes. The linearity of the calibration curve was good, with
      coefficients of determination (r(2) ) >0.9914 for all of the analytes. The
      developed method was successfully applied for the simultaneous determination of
      the three lignans in rat plasma following oral administration of Diphylleia
      sinensis extract to rats.

PMID- 24122913
TI  - Very large database of lipids: rationale and design.
AB  - Blood lipids have major cardiovascular and public health implications. Lipid
      lowering drugs are prescribed based in part on categorization of patients into
      normal or abnormal lipid metabolism, yet relatively little emphasis has been
      placed on: (1) the accuracy of current lipid measures used in clinical practice,
      (2) the reliability of current categorizations of dyslipidemia states, and (3)
      the relationship of advanced lipid characterization to other cardiovascular
      disease biomarkers. To these ends, we developed the Very Large Database of Lipids
      (NCT01698489), an ongoing database protocol that harnesses deidentified data from
      the daily operations of a commercial lipid laboratory. The database includes
      individuals who were referred for clinical purposes for a Vertical Auto Profile
      (Atherotech Inc., Birmingham, AL), which directly measures cholesterol
      concentrations of low-density lipoprotein, very low-density lipoprotein,
      intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and
      lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from
      studies of measurement accuracy, to dyslipidemia categorization, to biomarker
      associations, to characterization of rare lipid disorders, are investigator
      initiated and utilize peer-reviewed statistical analysis plans to address a
      priori hypotheses/aims. In the first database harvest (Very Large Database of
      Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric
      patients; the adult sample had a median age of 59 years (interquartile range, 49
      70 years) with even representation by sex. Lipid distributions closely matched
      those from the population-representative National Health and Nutrition
      Examination Survey. The second harvest of the database (Very Large Database of
      Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database
      provides an opportunity for collaboration and new knowledge generation through
      careful examination of granular lipid data on a large scale. 

PMID- 24122914
TI  - Avoidance and reproduction tests with the predatory mite Hypoaspis aculeifer:
      effects of different chemical substances.
AB  - Few toxicity data exist in the literature on the toxicity of chemicals to the
      predatory mite Hypoaspis aculeifer, but no information is available on its
      avoidance response. To assess the relevance of the avoidance behavior of H.
      aculeifer and the relative sensitivity of the mite in comparison with other
      invertebrates, avoidance and reproduction tests were conducted with 7 chemicals
      using standardized guidelines. The chemicals (deltamethrin, chloropyrifos,
      dimethoate, Cu, NaCl, phenanthrene, and boric acid) were selected so as to cover
      varying chemical classes. For all 3 pesticides tested, avoidance response showed
      lower sensitivity than reproduction and survival (avoidance median effective
      concentration [EC50] > reproduction EC50/median lethal concentration [LC50]
      values). However, for Cu, NaCl, and phenanthrene, the avoidance response showed
      similar sensitivity as reproduction (avoidance EC50 <= reproduction EC50 values),
      whereas for boric acid, similar sensitivity as survival (avoidance EC50 <= LC50
      values). Although the mite H. aculeifer appears less sensitive to some of the
      chemicals tested than most other soil invertebrates, its status as the only
      predator among organisms for which standardized tests are available affirms its
      inclusion in routine ecotoxicity assessment. The results of the avoidance test
      with H. aculeifer suggest its potential usefulness as a rapid screening test for
      risk assessment purposes.

PMID- 24122915
TI  - Sialendoscopy-assisted microsurgical repair of traumatic transection of Stensen's
      duct.
AB  - Sialendoscopy is established in the diagnostics and treatment of obstructive
      salivary gland diseases, but has not previously been reported in patients with
      injuries to Stensen's duct. Sialendoscopy assisted repair of a transected
      Stensen's duct in zone B is reported. The duct injury itself, its location, and
      its severity could be visualized and precisely assessed and allowed intraductal
      assessment of the ductal tissue. Rapid atraumatic dissection and also
      postoperative endoscopic follow-up examination with assessment of the anastomosis
      was provided by using the sialendoscope, which appears to be valuable for several
      reasons in the management of Stensen's duct trauma.

PMID- 24122916
TI  - Augmented real-time navigation with critical structure proximity alerts for
      endoscopic skull base surgery.
AB  - OBJECTIVES/HYPOTHESIS: Image-guided surgery (IGS) systems are frequently utilized
      during cranial base surgery to aid in orientation and facilitate targeted
      surgery. We wished to assess the performance of our recently developed localized
      intraoperative virtual endoscopy (LIVE)-IGS prototype in a preclinical setting
      prior to deployment in the operating room. This system combines real-time
      ablative instrument tracking, critical structure proximity alerts, three
      dimensional virtual endoscopic views, and intraoperative cone-beam computed
      tomographic image updates. STUDY DESIGN: Randomized-controlled trial plus
      qualitative analysis. METHODS: Skull base procedures were performed on 14 cadaver
      specimens by seven fellowship-trained skull base surgeons. Each subject performed
      two endoscopic transclival approaches; one with LIVE-IGS and one using a
      conventional IGS system in random order. National Aeronautics and Space
      Administration Task Load Index (NASA-TLX) scores were documented for each
      dissection, and a semistructured interview was recorded for qualitative
      assessment. RESULTS: The NASA-TLX scores for mental demand, effort, and
      frustration were significantly reduced with the LIVE-IGS system in comparison to
      conventional navigation (P < .05). The system interface was judged to be
      intuitive and most useful when there was a combination of high spatial demand,
      reduced or absent surface landmarks, and proximity to critical structures. The
      development of auditory icons for proximity alerts during the trial better
      informed the surgeon while limiting distraction. CONCLUSIONS: The LIVE-IGS system
      provided accurate, intuitive, and dynamic feedback to the operating surgeon.
      Further refinements to proximity alerts and visualization settings will enhance
      orientation while limiting distraction. The system is currently being deployed in
      a prospective clinical trial in skull base surgery.

PMID- 24122917
TI  - Toxic effects of a modified montmorillonite clay on the human intestinal cell
      line Caco-2.
AB  - The incorporation of the natural mineral clay montmorillonite into polymeric
      systems enhances their barrier properties as well as their thermal and mechanical
      resistance, making them suitable for a wide range of industrial applications,
      e.g., in the food industry. Considering humans could easily be exposed to these
      clays due to migration into food, toxicological and health effects of clay
      exposure should be studied. In the present work, the cytotoxic effects induced by
      two different clays (the unmodified clay Cloisite((r)) Na(+) , and the
      organically modified Cloisite((r)) 30B) on Caco-2 cells were studied after 24 and
      48 h of exposure. The basal cytotoxicity endpoints assessed were total protein
      content, neutral red uptake and a tetrazolium salt reduction. Our results showed
      that only Cloisite((r)) 30B induced toxic effects. Therefore, the effects of
      subcytotoxic concentrations of this clay on the generation of intracellular
      reactive oxygen species, glutathione content and DNA damage (comet assay) were
      investigated. Results indicate that oxidative stress may be implicated in the
      toxicity induced by Closite((r)) 30B, in regards of the increases in
      intracellular reactive oxygen species production and glutathione content at the
      highest concentration assayed, while no damage was observed in DNA. The most
      remarkable morphological alterations observed were dilated cisternae edge in the
      Golgi apparatus and nucleolar segregation, suggesting impairment in the secretory
      functions, which could be related to inhibition in the synthesis of proteins.

PMID- 24122918
TI  - Investigation of respiratory and dermal symptoms associated with metal working
      fluids at an aircraft engine manufacturing facility.
AB  - BACKGROUND: Each year, 1.2 million metalworkers are exposed to metalworking
      fluids (MWFs), which can cause dermal and respiratory disease. The National
      Institute for Occupational Safety and Health (NIOSH) conducted a health hazard
      evaluation of MWF exposures at an aircraft engine manufacturing facility. The
      objectives were to determine employee exposures to endotoxin and MWFs in the air,
      characterize symptoms experienced by employees working with MWFs, compare them to
      symptoms of employees unexposed to MWFs, and make recommendations for reducing
      exposures based on results. METHODS: Four hundred seven workers were categorized
      as MWF exposed or MWF unexposed and completed questionnaires. Estimated
      prevalence ratios (PR) of dermatitis, asthma, and work-related asthma (WRA)
      symptoms were calculated. Airborne concentrations of MWF and endotoxin were
      measured, and work practices observed. RESULTS: MWF exposed workers had a
      significantly higher prevalence of dermatitis on wrists/forearms (PR 2.59; 95% CI
      1.22, 5.46), asthma symptoms (PR 1.49; 95% CI 1.05, 2.13), and WRA symptoms (PR
      2.10; 95% CI 1.22, 3.30) than unexposed workers. Airborne concentrations of MWF
      were below the NIOSH recommended exposure limit (REL) for MWF aerosols (thoracic
      particulate mass). CONCLUSIONS: Despite MWF exposures below the NIOSH REL,
      exposed workers had a higher prevalence of asthma, WRA, and dermatitis symptoms
      than unexposed workers. Recommendations to reduce exposure included configuring
      mist collectors to automatically turn on when the machine is in use, and
      enforcing enclosure use.

PMID- 24122920
TI  - Napping helps preschoolers learn.

PMID- 24122921
TI  - Light-powered molecular logic goes nonlinear.

PMID- 24122922
TI  - Reply: To PMID 23213040.

PMID- 24122923
TI  - Improved outcome with hematopoietic stem cell transplantation in a poor
      prognostic subgroup of patients with mixed-lineage-leukemia-rearranged acute
      leukemia: Results from a prospective, multi-center study.
AB  - The purpose of this study is to define the role for allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in mixed-lineage-leukemia (MLL)-rearranged acute
      leukemia, which is now poorly understood. A prospective, multi-center cohort
      study to determine whether allo-HSCT could decrease relapse rates and improve
      long-term survival of MLL+ leukemia patients was performed. Fifty-six consecutive
      patients diagnosed with MLL-rearranged acute leukemia undergoing allo-HSCT from
      two transplant centers in China were enrolled between October 2007 and October
      2012. The trial was registered at www.chictr.org as # ChiCTR-ONC-12002739. The
      incidences of grades II to IV acute graft versus host disease (aGVHD) and of
      grades III and IV aGVHD were 28.8% (CI, 16.87-40.8%), and 14.2% (CI, 5.4-23.0%),
      respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after
      HSCT were 35.2% (CI, 21.2-49.2%). Up to April 30, 2013, 12 patients had relapsed
      and 11 died from relapse, and 37 patients were still alive without disease
      recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7-37.9%) and
      18.0% (CI, 2.6-33.4%), respectively. The probalities of overall survival and
      leukemia free survival were 61.8% (CI, 46.0-77.6%) and 56.3% (CI, 38.1-74.5%) at
      3 years, respectively. Patients transplanted during their hematological first
      complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03)
      compared with patients transplanted beyond CR1. The median overall survival for
      the 29 patients not receiving allo-HSCT during the study period was 145 days from
      diagnosis. This study showed that allo-HSCT could be a valuable treatment choice
      for MLL+ acute leukemia.

PMID- 24122924
TI  - Release of growth factors from a reinforced collagen GAG matrix supplemented with
      platelet rich plasma: Influence on cultured human meniscal cells.
AB  - Damage to meniscal cartilage has been strongly linked to accelerated articular
      wear and consequently to osteoarthritis. Damage might be ameliorated by delivery
      of growth factors from platelet rich plasma (PRP) via a fiber reinforced collagen
      matrix designed for meniscal repair. PRP composition, release of growth factors,
      and influence on meniscal cell growth and gene expression were investigated. PRP
      was prepared using Harvest Smartprep (HS-PRP), Cascade Fibrinet (CF-PRP), and a
      simple centrifuge protocol (DC-PRP) from four donors each. CF-PRP had the highest
      ratio of platelets, with very few other blood cell types. HS-PRP had the highest
      total number of platelets but also contained high levels of red and white blood
      cells. Absorbed to collagen matrices HS-PRP released the highest levels of TGF
      beta1 and PDGF-AB with DC-PRP the most IGF-1. Cumulative release from collagen
      matrix was 48 ng/cm(3) IGF-1, 96 ng/cm(3) TGF-beta1, and 9.6 ng/cm(3) PDGF-AB.
      Collagen matrix with PRP was able to increase meniscal cell number above
      peripheral whole blood and up-regulated gene expression of Aggrecan, Collagen
      type I (alpha1), and Elastin (3.3 +/- 0.8-fold, 2.9 +/- 0.6-fold, 4.0 +/- 1.4
      fold, respectively). Demonstrating that PRP combined with fiber reinforced
      collagen matrix could influence meniscal cells and might be of use for treating
      meniscal defects.

PMID- 24122925
TI  - Transplantation of iPSc ameliorates neural remodeling and reduces ventricular
      arrhythmias in a post-infarcted swine model.
AB  - Neural remodeling after myocardial infarction (MI) may cause malignant
      ventricular arrhythmia, which is the main cause of sudden cardiac death following
      MI. Herein, we aimed to examine whether induced pluripotent stem cells (iPSc)
      transplantation can ameliorate neural remodeling and reduce ventricular
      arrhythmias (VA) in a post-infarcted swine model. Left anterior descending
      coronary arteries were balloon-occluded to generate MI. Animals were then divided
      into Sham, PBS control, and iPS groups. Dynamic electrocardiography programmed
      electric stimulation were performed to evaluate VA. The spatial distribution of
      vascularization, Cx43 and autonomic nerve regeneration were evaluated by
      immunofluorescence staining. Associated protein expression was detected by
      Western blotting. Likewise, we measured the enzymatic activities of superoxide
      dismutase and content of malondialdehyde. Six weeks later, the number of blood
      vessels increased significantly in the iPSc group. The expression of vascular
      endothelial growth factor and connexin 43 in the iPS group was significantly
      higher than the PBS group; however, the levels of nerve growth factor and
      tyrosine hydroxylase were lower. The oxidative stress was ameliorated by iPSc
      transplantation. Moreover, the number of sympathetic nerves in the iPSc group was
      reduced, while the parasympathetic nerve fibers had no obvious change. The
      transplantation of iPSc also significantly decreased the low-/high-frequency
      ratio and arrhythmia score of programmed electric stimulation-induced VA. In
      conclusion, iPSc intramyocardial transplantation reduces vulnerability to VAs,
      and the mechanism was related to the remodeling amelioration of autonomic nerves
      and gap junctions. Moreover, possible mechanisms of iPSc transplantation in
      improving neural remodeling may be related to attenuated oxidative stress and
      inflammatory response.

PMID- 24122926
TI  - Regression analysis of multivariate current status data with dependent censoring:
      application to ankylosing spondylitis data.
AB  - Multivariate current-status failure time data consist of several possibly related
      event times of interest, in which the status of each event is determined at a
      single examination time. If the examination time is intrinsically related to the
      event times, the examination is referred to as dependent censoring and needs to
      be taken into account. Such data often occur in clinical studies and animal
      carcinogenicity experiments. To accommodate for possible dependent censoring,
      this paper proposes a joint frailty model for event times and dependent censoring
      time. We develop a likelihood approach using Gaussian quadrature techniques for
      obtaining maximum likelihood estimates. We conduct extensive simulation studies
      for investigating finite-sample properties of the proposed method. We illustrate
      the proposed method with an analysis of patients with ankylosing spondylitis,
      where the examination time may be dependent on the event times of interest.

PMID- 24122927
TI  - Bioavailability of copper in contaminated sediments assessed by a DGT approach
      and the uptake of copper by the aquatic plant Myriophyllum aquaticum.
AB  - The assessment of the potentially harmful effects of metals on biota depends on
      the speciation and bioavailability of the metals. In the present study, the
      authors investigated Cu accumulation and toxicity in the aquatic plant
      Myriophyllum aquaticum after exposure to artificial sediments varying in peat or
      ferric hydroxide content and spiked with Cu (5-200 mg kg(-1)). Modeling of the
      kinetic diffusive gradient in thin film (DGT) measurements revealed fast and slow
      Cu resupply from the solid phase for sediment formulated with and without peat,
      respectively. Myriophyllum aquaticum proved to be sensitive to Cu, as the Cu
      accumulation and growth differed depending on the sediment composition and Cu
      concentration. Comparing the Cu accumulation in M. aquaticum with total dissolved
      concentration, free concentration, and concentration in solution derived from DGT
      measurements (CDGT), Cu concentrations revealed that CDGT concentrations were a
      better predictor of accumulation than the others. However, the relatively weak
      correlation observed (r(2)  = 0.6) and the fact that plant uptake does not
      increase proportionally to DGT fluxes suggest that Cu uptake in plants was not
      diffusion limited. Thus, the free Cu concentrations near the root surface were
      sufficient to meet the plant's demand during the experiment. Furthermore, labile
      complexes that continuously resupply the Cu(2+) pool may also contribute to the
      concentrations available for plant uptake. In the range of Cu concentrations
      investigated in the present study, saturation of uptake processes as well as
      toxicity are considered responsible for the poor DGT prediction of plant uptake.

PMID- 24122928
TI  - Elucidating protein secondary structure with circular dichroism and a neural
      network.
AB  - Circular dichroism spectroscopy is a quick method for determining the average
      secondary structures of proteins, probing their interactions with their
      environment, and aiding drug discovery. This article describes the development of
      a self-organising map structure-fitting methodology named secondary structure
      neural network (SSNN) to aid this process and reduce the level of expertise
      required. SSNN uses a database of spectra from proteins with known X-ray
      structures; prediction of structures for new proteins is then possible. It has
      been designed as 3 units: SSNN1 takes spectra for known proteins, clusters them
      into a map, and SSNN2 creates a matching structure map. SSNN3 places unknown
      spectra on the map and gives them structure vectors. SSNN3 output illustrates the
      process and results obtained. We detail the strengths and weaknesses of SSNN and
      compare it with widely accepted structure fitting programs. Current input format
      is Deltaepsilon per amino acid residue from 240 to 190 nm in 1 nm steps for the
      known and unknown proteins and a vector summarizing the secondary structure
      elements of the known proteins. The format is readily modified to include input
      data with, for example, extended wavelength ranges or different assignment of
      secondary structures. SSNN can be used either pretrained with a reference set
      from the CDPro web site (direct application of SSNN3, with the provided output
      from SSNN1 and SSNN2) or all three modules can be used as required. SSNN3 is
      available trained (with the reference set of the 48-spectra set used in this work
      complemented by five additional spectra) at
      http://www2.warwick.ac.uk/fac/sci/chemistry/research/arodger/arodgergroup/researc
      _intro/instrumentation/ssnn/.

PMID- 24122929
TI  - Opioid poisonings and opioid adverse effects in workers in Washington state.
AB  - OBJECTIVE: To examine trends in opioid poisonings and adverse effects in
      Washington (WA) State and nationally. METHODS: We calculated rates of opioid
      poisonings and adverse effects and examined opioid prescriptions in the WA
      workers' compensation system, 2004-2010. Using Health Care Cost and Utilization
      Project (HCUP), Nationwide Inpatient Sample (NIS) data, we also calculated
      national rates of opioid poisonings and adverse effects, 1993-2010. RESULTS: We
      identified 96 opioid poisonings and 312 opioid-related adverse effects in WA,
      2004-2010. The rates did not change substantially over these years. Most
      poisonings and adverse effects occurred in cases without chronic opioid use and
      with prescribed doses <120 mg/day morphine-equivalent dose. Nationally, the rates
      of opioid poisonings and adverse effects increased significantly from 1993 to
      2010. CONCLUSIONS: Many poisonings and adverse effects occurred in patients
      without high dose or long-term opioid therapy, suggesting that opioid dosing and
      duration guidelines may not be sufficient to reduce morbidity related to
      prescription opioid use.

PMID- 24122930
TI  - Lower admission hemoglobin levels are associated with longer symptom duration in
      acute ST-elevation myocardial infarction.
AB  - BACKGROUND: An acute-phase response in patients with acute myocardial infarction
      could contribute to the development of anemia. HYPOTHESIS: An association may
      exist between symptom duration, hemoglobin (Hb) concentration and serum C
      reactive protein (CRP) values in patients presenting to an emergency department
      (ED) with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A
      retrospective analysis was conducted on consecutive male STEMI patients who were
      admitted to our medical center's ED from January 2008 to November 2012 and had
      presented within the first 12 hours after the onset of chest pain. Hemoglobin
      concentration and serum CRP levels were determined from blood samples taken prior
      to any drug or fluid administration. Analyses of variance were used to determine
      interactions between selected time-to-presentation cutoffs and admission Hb and
      CRP concentrations. Patients with other reasons known to cause elevation of
      inflammatory markers, anemia, or bleeding diathesis were excluded. RESULTS: The
      study population comprised 718 patients whose mean age was 61 +/- 12 years
      (range, 27-96 years). Blood was drawn for Hb and CRP measurements directly upon
      admission. Patients who presented to the ED within 3 hours of symptom onset had
      higher Hb concentrations (P = 0.048) and lower serum CRP levels (P < 0.001)
      compared with those who presented after a longer interval from symptom onset.
      CONCLUSIONS: Longer symptom duration is associated with a lower admission Hb
      level and an early rise in the CRP level of male patients with acute STEMI.

PMID- 24122931
TI  - Effects of botulinum toxin type A on non-injected bi-articular muscle include a
      narrower length range of force exertion and increased passive force.
AB  - INTRODUCTION: The goal of this study was to test the hypothesis that botulinum
      toxin type A (BTX-A) injection in rat tibialis anterior (TA) muscle affects the
      mechanics of its bi-articular synergist, both actively and passively. METHODS:
      Two groups of Wistar rats were tested: control (no BTX-A) and BTX (0.1 U of BTX
      A) animals were injected exclusively to the mid-belly of TA. Extensor digitorum
      longus (EDL) muscle isometric forces were measured after proximal and distal
      lengthening. RESULTS: Five days after injection, BTX-A administration changed EDL
      mechanics: (1) active forces decreased (proximal muscle length dependently); (2)
      length range of active force exertion decreased both proximally and distally; and
      (3) passive muscle forces increased. CONCLUSIONS: Effects of BTX-A appear to not
      be limited to decreased active muscle tone, but may cause also a narrower active
      range of movement and increased passive resistance. Through spread of BTX-A to a
      bi-articular muscle, such effects are plausible for both joints spanned.

PMID- 24122932
TI  - Functional echocardiography in the fetus with non-cardiac disease.
AB  - We describe the hemodynamic changes observed in fetuses with extra cardiac
      conditions such as intrauterine growth restriction, tumors, twin-twin transfusion
      syndrome, congenital infections, and in fetuses of mothers with diabetes. In most
      fetuses with mild extra cardiac disease, the alterations in fetal cardiac
      function remain subclinical. Cardiac function assessment has however helped us to
      achieve a better understanding of the pathophysiology of these diseases. In
      fetuses at the more severe end of the disease spectrum, functional
      echocardiography may help in guiding clinical decision-making regarding the need
      for either delivery or fetal therapy. The growth-restricted fetus represents a
      special indication for routine cardiac function assessment, as in utero
      hemodynamic changes may help optimize the timing of delivery. Moreover, in
      intrauterine growth restriction, the altered hemodynamics causes cardiovascular
      remodeling, which can result in an increased risk of postnatal cardiovascular
      disease.

PMID- 24122934
TI  - Reply: To PMID 23661325.

PMID- 24122933
TI  - Tri-iodothyronine induces hepatocyte proliferation by protein kinase A-dependent
      beta-catenin activation in rodents.
AB  - Thyroid hormone (T3), like many other ligands of the steroid/thyroid hormone
      nuclear receptor superfamily, is a strong inducer of liver cell proliferation in
      rats and mice. However, the molecular basis of its mitogenic activity, which is
      currently unknown, must be elucidated if its use in hepatic regenerative medicine
      is to be considered. F-344 rats or C57BL/6 mice were fed a diet containing T3 for
      2-7 days. In rats, administration of T3 led to an increased cytoplasmic
      stabilization and nuclear translocation of beta-catenin in pericentral
      hepatocytes with a concomitant increase in cyclin-D1 expression. T3
      administration to wild-type (WT) mice resulted in increased hepatocyte
      proliferation; however, no mitogenic response in hepatocytes to T3 was evident in
      the hepatocyte-specific beta-catenin knockout mice (KO). In fact, T3 induced beta
      catenin-TCF4 reporter activity both in vitro and in vivo. Livers from T3-treated
      mice demonstrated no changes in Ctnnb1 expression, activity of glycogen synthase
      kinase-3beta, known to phosphorylate and eventually promote beta-catenin
      degradation, or E-cadherin-beta-catenin association. However, T3 treatment
      increased beta-catenin phosphorylation at Ser675, an event downstream of protein
      kinase A (PKA). Administration of PKA inhibitor during T3 treatment of mice and
      rats as well as in cell culture abrogated Ser675-beta-catenin and simultaneously
      decreased cyclin-D1 expression to block hepatocyte proliferation. CONCLUSION: We
      have identified T3-induced hepatocyte mitogenic response to be mediated by PKA
      dependent beta-catenin activation. Thus, T3 may be of therapeutic relevance to
      stimulate beta-catenin signaling to in turn induce regeneration in selected cases
      of hepatic insufficiency.

PMID- 24122935
TI  - Transnasal endoscopic resection of symptomatic ecchordosis physaliphora.

PMID- 24122936
TI  - Cortisone induces insulin resistance in C2C12 myotubes through activation of
      11beta-hydroxysteroid dehydrogenase 1 and autocrinal regulation.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is known to
      catalyse inactive glucocorticoids into active forms, and its dysregulation in
      adipose and muscle tissues has been implicated in the development of metabolic
      syndrome. To delineate the molecular mechanism by which active cortisol has an
      antagonizing effect against insulin, we optimized the metabolic production of
      cortisol and its biological functions in myotubes (C2C12). Myotubes supplemented
      with cortisone actively catalysed its conversion into cortisol, which in turn
      abolished phosphorylation of Akt in response to insulin treatment. This led to
      diminished uptake of insulin-induced glucose. This was corroborated by the
      application of 11beta-HSD1 inhibitor glycyrrhetinic acid and a glucocorticoid
      receptor antagonist RU-486, which reversed completely the antagonizing effects of
      cortisol on insulin action. Therefore, development of specific inhibitors
      targeting 11beta-HSD1 might be a promising way to improve impaired insulin
      stimulated glucose uptake.

PMID- 24122937
TI  - Dried blood spots for HIV-1 drug resistance genotyping in decentralized settings
      in Senegal.
AB  - The aim of this study was to evaluate the use for HIV-1 drug resistance testing
      dried blood spots collected in remote areas and sent under field conditions to a
      reference laboratory and also to document virological failure in patients with
      suspected treatment failure. Samples were collected from patients receiving first
      line ART at 11 hospital sites around country, kept at room temperature (<37
      degrees C) and sent within 15 days maximum to the reference laboratory. Viral
      nucleic acids were obtained by magnetic extraction with NucliSENS (bioMerieux,
      Marcy l'Etoile, France). Genotyping of HIV-1 pol gene was performed using the
      ANRS protocol. Drug resistance mutations were analyzed according to the Stanford
      University HIV database version 6.0.8. Two hundred thirty one HIV-infected
      adults' on HAART first line regimen composed study population. The median time on
      ART was 18 months (range 6-68). Regardless of the treatment duration, the overall
      rate of virological failure (VL >= 3 log10  cp/ml) was 23.8% (n = 55/231). HIV
      genotypes were obtained successfully in 94.5% (n = 52/55). Drug resistance
      mutation was found in 41/52 patients in virological failure, for 17.7% (n =
      41/231) an overall rate of drug resistance mutations. M184V/I was the most
      frequent mutation occurring, followed by K103N. Phylogenetic analysis of the 52
      genotyped viral isolates showed the predominance of CRF02_AG with 62% (n =
      32/52). Use of a DBS specimen is suitable to assist national programs for
      monitoring in remote areas HIV drug resistance in resources limited-settings.

PMID- 24122938
TI  - Flow cytometry analyses reveal association between Lu/BCAM adhesion molecule and
      osteonecrosis in sickle cell disease.

PMID- 24122939
TI  - Simultaneous determination of four components in Baige capsule by HPLC:
      application to pharmacokinetics and tissue distribution of normal and middle
      cerebral artery occlusion rats.
AB  - A sensitive and specific high-performance liquid chromatography (HPLC) method was
      developed and applied to the pharmacokinetics for simultaneous identification and
      quantification of four components - puerarin, daidzein, imperatorin and
      isoimperatorin - in the plasma and tissues of normal and middle cerebral artery
      occlusion rats after oral administration of Baige capsule. Ferulic was used as
      the internal standard. The extraction procedure was composed of two independent
      steps. The plasma was prepared by liquid-liquid extraction with light petroleum
      acetic ether (1:1, v/v) first and then protein was precipitated with methanol.
      The tissue samples were weighted and homogenated with normal saline, then the
      homogenate was prepared by liquid-liquid extraction and protein precipitation.
      The parameters of pharmacokinetics were calculated using DAS 2.1.1 software. The
      calibration curves of all four components in the plasma and tissue homogenates
      were in good linearity in the measured range with R(2)  >= 0.9921. The relative
      standard deviation of the intra- and inter-day accuracy at different levels was
      less than +/-18.0%. In conclusion, the established method was a simple and
      effective one to simultaneously detect all four components in the plasma and
      tissues of rats, and was successfully applied in the pharmacokinetics of Baige
      capsule.

PMID- 24122940
TI  - Nanotopography drives stem cell fate toward osteoblast differentiation through
      alpha1beta1 integrin signaling pathway.
AB  - The aim of our study was to investigate the osteoinductive potential of a
      titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs)
      and the mechanism involved in this phenomenon. Polished Ti discs were chemically
      treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured
      under osteogenic and non-osteogenic conditions on both nanotopography and
      untreated polished (control) Ti surfaces. The nanotopography increased cell
      proliferation and alkaline phosphatase (Alp) activity and upregulated the gene
      expression of key bone markers of cells grown under both osteogenic and non
      osteogenic conditions. Additionally, the gene expression of alpha1 and beta1
      integrins was higher in cells grown on Ti with nanotopography under non
      osteogeneic condition compared with control Ti surface. The higher gene
      expression of bone markers and Alp activity induced by Ti with nanotopography was
      reduced by obtustatin, an alpha1beta1 integrin inhibitor. These results indicate
      that alpha1beta1 integrin signaling pathway determines the osteoinductive effect
      of nanotopography on MSCs. This finding highlights a novel mechanism involved in
      nanosurface-mediated MSCs fate and may contribute to the development of new
      surface modifications aiming to accelerate and/or enhance the process of
      osseointegration.

PMID- 24122941
TI  - Oxidative stress responses of gulf killifish exposed to hydrocarbons from the
      Deepwater Horizon oil spill: Potential implications for aquatic food resources.
AB  - Ecosystem effects of polycyclic aromatic hydrocarbons (PAHs) remain under
      investigation following the Gulf of Mexico Deepwater Horizon oil spill. Fundulus
      grandis, an established indicator of aquatic ecosystem health, was investigated
      because this species shares genes and biochemical pathways with higher trophic
      level fish and plays an important role in the gulf food chain. Oxidative stress
      responses including hepatic cytochrome P4501A (CYP1A) and serum antioxidant
      capacity were evaluated in fish exposed to PAHs. Fish were exposed to water
      accommodated fractions (WAFs) of crude oil (7.0  +/- 0.10 mg/L C6-C28) after
      which solutions were diluted below the level of detection over 8 h using 15 ppt
      aerated artificial seawater. Before euthanasia, fish remained in aquaria for 12
      h, 24 h, or 48 h. Three replicate experiments were conducted at each time point
      using unexposed fish as experimental controls. Significant differences (p < 0.05)
      in CYP1A induction were observed in exposed versus control fish at 24 h.
      Expression of CYP1A increased by 25%, 66%, and 23% in exposed fish at 12 h, 24 h,
      and 48 h, respectively. Significant increases were observed in antioxidant
      capacity of nonenzymatic antioxidants in exposed versus control fish at each time
      point. Given the activity of CYP1A, radicals formed during PAH detoxification
      likely resulted in increased oxidant load requiring elevated antioxidant
      defenses. Research is needed to determine the duration of oxidative stress
      responses considering the potential for lipid oxidation in exposed fish or
      species feeding on exposed fish.

PMID- 24122942
TI  - Biomechanical comparison of fixed- and mobile-bearing for unicomparmental knee
      arthroplasty using finite element analysis.
AB  - Unicomparmental knee arthroplasty (UKA) is a popular alternative to total knee
      arthroplasty (TKA) and high tibial osteotomy for unicompartmental knee
      conditions, especially in young patients. However, failure of UKA occurs due to
      either progressive osteoarthritis (OA) in the other compartment or wear on the
      polyethylene (PE) insert. This study used finite element (FE) analysis to
      investigate the effects of PE insert contact pressure and stress in opposite
      compartments for fixed- and mobile-bearing UKA. Analysis was performed using high
      kinematics displacement and rotation inputs, which were based on the kinematics
      of the natural knee. ISO standards were used for axial load and flexion. The
      mobile-bearing PE insert had lower contact pressure than the fixed-bearing PE
      insert. With the mobile-bearing UKA, lower stress on the opposite compartment
      reduces the overall risk of progressive OA in the knee. The fixed-bearing UKA
      increases the overall risk of progressive OA in the knee due to higher stress on
      the opposite compartment. However, the PE insert of mobile-bearing showed
      pronounced backside stress at the inferior surface.

PMID- 24122943
TI  - On the estimation of the reproduction number based on misreported epidemic data.
AB  - Epidemic data often suffer from underreporting and delay in reporting. In this
      paper, we investigated the impact of delays and underreporting on estimates of
      reproduction number. We used a thinned version of the epidemic renewal equation
      to describe the epidemic process while accounting for the underlying reporting
      system. Assuming a constant reporting parameter, we used different delay patterns
      to represent the delay structure in our model. Instead of assuming a fixed delay
      distribution, we estimated the delay parameters while assuming a smooth function
      for the reproduction number over time. In order to estimate the parameters, we
      used a Bayesian semiparametric approach with penalized splines, allowing both
      flexibility and exact inference provided by MCMC. To show the performance of our
      method, we performed different simulation studies. We conducted sensitivity
      analyses to investigate the impact of misspecification of the delay pattern and
      the impact of assuming nonconstant reporting parameters on the estimates of the
      reproduction numbers. We showed that, whenever available, additional information
      about time-dependent underreporting can be taken into account. As an application
      of our method, we analyzed confirmed daily A(H1N1) v2009 cases made publicly
      available by the World Health Organization for Mexico and the USA.

PMID- 24122944
TI  - Early-stage comparative effectiveness: randomized controlled trial with histamine
      inverse agonist MK-7288 in excessive daytime sleepiness patients.
AB  - Histaminergic neurons are regulators of the sleep-wake cycle. We evaluated the
      alerting effects of MK-7288 (10, 20 mg), a novel histamine-3 receptor inverse
      agonist (H3RIA), along with modafinil (200 mg), a standard treatment, in a
      randomized, double-blind, placebo controlled, crossover study of 56 patients with
      excessive daytime sleepiness (EDS). Efficacy was assessed using maintenance of
      wakefulness tests (MWT) and car driving simulation tests. MK-7288 and modafinil
      significantly prolonged MWT sleep latency (improvements vs. placebo of 8.1 to 8.2
      min for MK-7288 and 10.2 min for modafinil), and improved car driving simulation
      standard deviation of lane position (reduction vs. placebo of -0.1 m for each
      treatment). MK-7288 was associated with more insomnia (29%) than modafinil (9%)
      and placebo (6%). The study demonstrated the potential of the H3RIA mechanism for
      treating EDS, but did not show efficacy differentiation from modafinil. Early
      stage comparative effectiveness can help prevent late-stage failure and increase
      the cost-effectiveness of drug development. 

PMID- 24122945
TI  - Power calculation for overall hypothesis testing with high-dimensional
      commensurate outcomes.
AB  - The complexity of system biology means that any metabolic, genetic, or proteomic
      pathway typically includes so many components (e.g., molecules) that statistical
      methods specialized for overall testing of high-dimensional and commensurate
      outcomes are required. While many overall tests have been proposed, very few have
      power and sample size methods. We develop accurate power and sample size methods
      and software to facilitate study planning for high-dimensional pathway analysis.
      With an account of any complex correlation structure between high-dimensional
      outcomes, the new methods allow power calculation even when the sample size is
      less than the number of variables. We derive the exact (finite-sample) and
      approximate non-null distributions of the 'univariate' approach to repeated
      measures test statistic, as well as power-equivalent scenarios useful to
      generalize our numerical evaluations. Extensive simulations of group comparisons
      support the accuracy of the approximations even when the ratio of number of
      variables to sample size is large. We derive a minimum set of constants and
      parameters sufficient and practical for power calculation. Using the new methods
      and specifying the minimum set to determine power for a study of metabolic
      consequences of vitamin B6 deficiency helps illustrate the practical value of the
      new results. Free software implementing the power and sample size methods applies
      to a wide range of designs, including one group pre-intervention and post
      intervention comparisons, multiple parallel group comparisons with one-way or
      factorial designs, and the adjustment and evaluation of covariate effects.

PMID- 24122946
TI  - Coupled-cluster reaction barriers of HO2+H2O+O3: An application of the coupled
      cluster//Kohn-Sham density functional theory model chemistry.
AB  - In this work, we report a theoretical investigation concerning the use of the
      popular coupled-cluster//Kohn-Sham density functional theory (CC//KS-DFT) model
      chemistry, here applied to study the entrance channel of the HO2+H2O+O3 reaction,
      namely by comparing CC//KS-DFT calculations with KS-DFT, MRPT2//CASSCF, and
      CC//CASSCF results from our previous investigations. This was done by performing
      single point energy calculations employing several coupled cluster methods and
      using KS-DFT geometries optimized with six different functionals, while
      conducting a detailed analysis of the barrier heights and topological features of
      the curves and surfaces here obtained. The quality of this model chemistry is
      critically discussed in the context of the title reaction and also in a wider
      context.

PMID- 24122947
TI  - Safe-dose thrombolysis plus rivaroxaban for moderate and severe pulmonary
      embolism: drip, drug, and discharge.
AB  - BACKGROUND: Thrombolysis, though very effective, has not been embraced as routine
      therapy for symptomatic pulmonary embolism (PE) except in very severe cases.
      Rivaroxaban recently has been approved for the treatment of venous
      thromboembolism (VTE). There are no data on the combined use of thrombolysis and
      rivaroxaban in PE. HYPOTHESIS: "Safe dose" thrombolysis (SDT) plus new oral
      anticoagulants are expected to become an appealing, safe and effective approach
      in the treatment of moderate and severe PE in the near future, thereby
      drastically reducing hospitalization time. METHODS: Over a 12-month period, 98
      consecutive patients with symptomatic PE were treated by a combination of SDT and
      rivaroxaban. The SDT was started in parallel with unfractionated heparin and
      given in 2 hours. Heparin was given for a total of 24 hours and rivaroxaban
      started at 15 or 20 mg daily 2 hours after termination of heparin infusion.
      RESULTS: There was no bleeding due to SDT. Recurrent VTE occurred in 3 patients
      who had been switched to warfarin. No patient on rivaroxaban developed VTE. Two
      patients died of cancer at a mean follow-up of 12 +/- 2 months. The pulmonary
      artery systolic pressure dropped from 52.8 +/- 3.9 mm Hg before to 32 +/- 4.4 mm
      Hg within 36 hours of SDT (P < 0.001). The duration of hospitalization for
      patients presenting primarily for PE was 1.9 +/- 0.2 days. CONCLUSIONS: "Safe
      dose" thrombolysis plus rivaroxaban is highly safe and effective in the treatment
      of moderate and severe PE, leading to favorable early and intermediate-term
      outcomes and early discharge.

PMID- 24122948
TI  - Ten-year health-related quality of life in cochlear implant recipients:
      prospective SF-36 data with SF-6D conversion.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the long-term impact of cochlear implantation
      on quality of life measured by the Medical Outcomes Study 36-Item Short-Form
      Health Survey (SF-36). Scores were also converted to the SF-6D to derive health
      utility scores. STUDY DESIGN: Prospective cohort study. METHODS: Thirty-two
      patients undergoing cochlear implantation completed the SF-36 preoperatively, 1
      year, and 10 years after cochlear implantation. RESULTS: SF-36 results showed
      improvements in seven of the eight attributes when preoperative scores where
      compared with 1- and 10-year results. Between 1 and 10 years postoperatively, six
      of eight domains deteriorated in scores. When converted to the SF-6D, the mean
      preoperative utility scores were 0.592 for standard gamble, 0.636 using the
      ordinal health state paradigm, and 0.579 using the Bayesian technique. Ten years
      postoperatively, health utility scores were 0.643 (standard gamble), 0.684
      (ordinal health state), and 0.6 (Bayesian). Between preoperatively and 10-year
      postoperatively, improvements were therefore 0.051, 0.048, and 0.021 for standard
      gamble, ordinal health state, and Bayesian paradigm, respectively. CONCLUSIONS:
      This study establishes the long-term sustained benefits of cochlear implantation
      on quality of life. Nevertheless, both the SF-36 and SF-6D seem to underestimate
      the benefit accrued through this intervention. Our data are consistent with
      others regarding the unsuitability of the SF-36 in benefit assessment,
      notwithstanding that conversion to the SF-6D is feasible, and the SF-6D seemed to
      better depict possible benefits from cochlear implantation as compared to the SF
      36.

PMID- 24122949
TI  - Migrated Essure permanent birth control device: sonographic findings.
AB  - We report a case of a migrated Essure permanent birth control device. The correct
      diagnosis was made on conventional two-dimensional and three-dimensional pelvic
      sonography 7 years after placement of the device when the patient presented with
      persistent right-sided pain. The 3-month post placement hysterosalpingogram had
      shown an appropriately occluded right fallopian tube but had overlooked the
      abnormal position of the right Essure device, which was too proximal and
      extending slightly in the uterine cavity.

PMID- 24122950
TI  - Improved quantification of myocardial blood flow using highly constrained back
      projection reconstruction.
AB  - PURPOSE: To improve quantification of myocardial blood flow using a fast T1
      mapping technique using highly constrained back projection reconstruction (HYPR)
      accelerated acquisition. METHODS: A major source of error in the measurement of
      myocardial blood flow (MBF) using MRI is the nonlinear relationship between image
      signal intensity and contrast agent (CA) concentration. HYPR-accelerated radial
      acquisition was used to generate pixel-wise T1 maps with a temporal resolution of
      one heartbeat. HYPR produces images with a temporal footprint of 40 ms and four
      images within 188 ms. T1 values were converted into CA concentrations by the
      known linear relationship between CA concentration and T1 . The T1 mapping
      technique was used to quantify MBF in 10 healthy subjects and compared with MBF
      found using image signal intensity as well as MBF reported in the literature.
      RESULTS: The MBF measured using the proposed method was more consistent with that
      previously reported in the literature and was significantly lower (P = 0.002)
      than that calculated using image signal intensity (1.11 +/- 0.27 mL/min/g versus
      1.88 +/- 0.45 mL/min/g, respectively). CONCLUSION: We developed a fast T1 mapping
      method for MBF quantification using radial sampling and HYPR. Further validation
      is required to determine its clinical value in assessing myocardial perfusion
      deficit in coronary artery disease.

PMID- 24122951
TI  - Assessment of electric field distribution in anisotropic cortical and subcortical
      regions under the influence of tDCS.
AB  - The focus of this study is to estimate the contribution of regional anisotropic
      conductivity on the spatial distribution of an induced electric field across gray
      matter (GM), white matter (WM), and subcortical regions under transcranial direct
      current stimulation (tDCS). The assessment was conducted using a passive high
      resolution finite element head model with inhomogeneous and variable anisotropic
      conductivities derived from the diffusion tensor data. Electric field
      distribution was evaluated across different cortical as well as subcortical
      regions under four bicephalic electrode configurations. Results indicate that
      regional tissue heterogeneity and anisotropy cause the pattern of induced fields
      to vary in orientation and strength when compared to the isotropic scenario.
      Different electrode montages resulted in distinct distribution patterns with
      noticeable variations in field strengths. The effect of anisotropy is highly
      montage dependent and directional conductivity has a more profound effect in
      defining the strength of the induced field. The inclusion of anisotropy in the GM
      and subcortical regions has a significant effect on the strength and spatial
      distribution of the induced electric field. Under the (C3-Fp2) montage, the
      inclusion of GM and subcortical anisotropy increased the average percentage
      difference in the electric field strength of brain from 5% to 34% (WM anisotropy
      only). In terms of patterns distribution, the topographic errors increased from
      9.9% to 40% (WM anisotropy only) across the brain.

PMID- 24122952
TI  - Choosing wisely: highest cost tests in outpatient neurology.

PMID- 24122953
TI  - Ascites and serum sodium are markers of increased waiting list mortality in
      children with chronic liver failure.
AB  - Ascites is the most common complication of cirrhosis and in adults it is
      associated with 50% mortality at 5 years if patients do not receive a liver
      transplant. The occurrence of hyponatremia in these patients has been associated
      with increased mortality on the waiting list. The importance of serum sodium
      levels and the presence of ascites in the pediatric setting remain to be
      clarified. A retrospective analysis of pediatric patients with cirrhosis on the
      transplant list was carried out between October 2000 and February 2012. The
      primary objective of this study was to evaluate the association of pretransplant
      variables with mortality within 90 days following the inclusion of patients on
      the waiting list. In all, 522 patients were included in the study; 345 (66%)
      patients were under 1 year of age; 208 (40%) of the children presented ascites. A
      multivariate Cox proportional hazards analysis was conducted and total bilirubin
      (P < 0.001, hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.35-3.21),
      international normalized ratio (INR) (P < 0.001, HR = 9.83, 95% CI = 4.51-21.45),
      serum sodium levels (P = 0.03, HR = 0.96, 95% CI = 0.92-0.99), ascites (P =
      0.001, HR = 2.59, 95% CI = 1.44-4.64), and categorized age (0-1 versus >= 1 year
      old) (P = 0.025, HR = 2.33, 95% CI = 1.11-4.86) were independently associated
      with risk of death in 90 days. Malnutrition (Z score height/age, weight/age) and
      serum albumin (pediatric endstage liver disease [PELD] formula) were not included
      in the final model. CONCLUSION: The presence of ascites and serum sodium levels
      are important variables associated with decreased patient survival while
      candidates wait for a liver graft. Multicenter studies are necessary to validate
      these findings in order to improve current allocation policies based on the PELD
      score.

PMID- 24122954
TI  - 'Not another safety culture survey': using the Canadian patient safety climate
      survey (Can-PSCS) to measure provider perceptions of PSC across health settings.
AB  - BACKGROUND: The importance of a strong safety culture for enhancing patient
      safety has been stated for over a decade in healthcare. However, this complex
      construct continues to face definitional and measurement challenges. Continuing
      improvements in the measurement of this construct are necessary for enhancing the
      utility of patient safety climate surveys (PSCS) in research and in practice.
      This study examines the revised Canadian PSCS (Can-PSCS) for use across a range
      of care settings. METHODS: Confirmatory factor analytical approaches are used to
      extensively test the Can-PSCS. Initial and cross-validation samples include 13
      126 and 6324 direct care providers from 119 and 35 health settings across Canada,
      respectively. RESULTS: Results support a parsimonious model of direct care
      provider perceptions of patient safety climate (PSC) with 19 items in six
      dimensions: (1) organisational leadership support for safety; (2) incident follow
      up; (3) supervisory leadership for safety; (4) unit learning culture; (5)
      enabling open communication I: judgement-free environment; (6) enabling open
      communication II: job repercussions of error. Results also support the validity
      of the Can-PSCS across a range of care settings. CONCLUSIONS: The Can-PSCS has
      several advantages: (1) it is a theory-based instrument with a small number of
      actionable dimensions central to the construct of PSC; (2) it has robust
      psychometric properties; (3) it is validated for use across a range of care
      settings, therefore suitable for use in regionalised health delivery systems and
      can help to raise expectations about acceptable levels of PSC across the system;
      (4) it has been tested in a publicly funded universal health insurance system and
      may be suitable for similar international systems.

PMID- 24122956
TI  - A molecular method for assessing the effects of potential contaminants on the
      rate of zebrafish (Danio rerio) development.
AB  - Monitoring expression of the developmentally regulated genes shh, sox2, and tnnt1
      by reverse transcriptase polymerase chain reaction (RT-PCR) allows determination
      of the rate of embryogenesis in zebrafish (Danio rerio) embryos without direct
      visual observation. The utility of combining this approach and morphological
      methods during toxicity studies was demonstrated with embryos developing at
      either 28.5  degrees C or 24.5  degrees C and with embryos exposed to sublethal
      doses of silver nanoparticles.

PMID- 24122955
TI  - Evaluation and management of anemia in the elderly.
AB  - Anemia is now recognized as a risk factor for a number of adverse outcomes in the
      elderly, including hospitalization, morbidity, and mortality. What constitutes
      appropriate evaluation and management for an elderly patient with anemia, and
      when to initiate a referral to a hematologist, are significant issues. Attempts
      to identify suggested hemoglobin levels for blood transfusion therapy have been
      confounded for elderly patients with their co-morbidities. Since no specific
      recommended hemoglobin threshold has stood the test of time, prudent transfusion
      practices to maintain hemoglobin thresholds of 9-10 g/dL in the elderly are
      indicated, unless or until evidence emerges to indicate otherwise.

PMID- 24122957
TI  - p62/SQSTM1 is required for cell survival of apoptosis-resistant bone metastatic
      prostate cancer cell lines.
AB  - BACKGROUND: Bone marrow stromal cell (BMSC) paracrine factor(s) can induce
      apoptosis in bone metastatic prostate cancer (PCa) cell lines. However, the PCa
      cells that escape BMSC-induced apoptosis can upregulate cytoprotective autophagy.
      METHODS: C4-2, C4-2B, MDA PCa 2a, MDA PCa 2b, VCaP, PC3, or DU145 PCa cell lines
      were grown in BMSC conditioned medium and analyzed for mRNA and/or protein
      accumulation of p62 (also known as sequestome-1/SQSTM1), Microtubule-associated
      protein 1 light chain 3B (LC3B), or lysosomal-associated membrane protein 1
      (LAMP1) using quantitative polymerase chain reaction (QPCR), Western blot, or
      immunofluorescence. Small interfering RNA (siRNA) was used to determine if p62 is
      necessary PCa cell survival. RESULTS: BMSC paracrine signaling upregulated p62
      mRNA and protein in a subset of the PCa cell lines. The PCa cell lines that were
      insensitive to BMSC-induced apoptosis and autophagy induction had elevated basal
      p62 mRNA and protein. In the BMSC-insensitive PCa cell lines, siRNA knockdown of
      p62 was cytotoxic and immunostaining showed peri-nuclear clustering of
      autolysosomes. However, in the BMSC-sensitive PCa cell lines, p62 siRNA knockdown
      was not appreciably cytotoxic and did not affect autolysosome subcellular
      localization. CONCLUSIONS: A pattern emerges wherein the BMSC-sensitive PCa cell
      lines are known to be osteoblastic and express the androgen receptor, while the
      BMSC-insensitive PCa cell lines are characteristically osteolytic and do not
      express the androgen receptor. Furthermore, BMSC-insensitive PCa may have evolved
      a dependency on p62 for cell survival that could be exploited to target and kill
      these apoptosis-resistant PCa cells in the bone.

PMID- 24122958
TI  - miRNA27a is a biomarker for predicting chemosensitivity and prognosis in
      metastatic or recurrent gastric cancer.
AB  - We previously identified five miRNAs (miR-1, miR-20a, miR-27a, miR-34a, and miR
      423-5p) that are up-regulated in gastric cancer. The goal of this study was to
      investigate the value of these miRNAs as potential biomarkers for predicting
      chemosensitivity and prognosis in metastatic or recurrent gastric cancer patients
      who received first-line chemotherapy. A total of 82 patients with metastatic or
      recurrent GC receiving first-line chemotherapy were included in our study. The
      expression levels of the five miRNAs were evaluated using hydrolysis probe-based
      stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR)
      in individual samples before first-line chemotherapy. Patients receiving first
      line chemotherapy with fluoropyrimidine combined with oxaliplatin or paclitaxel
      were chosen for the chemosensitivity analysis. The relationships between
      expression of the five-miRNAs and clinicopathological parameters, response to
      chemotherapy and prognosis were analyzed statistically. Patients with higher
      miRNA1 expression levels tended to have a higher rate of liver metastasis, and
      higher miRNA34a expression levels occurred more frequently in males (P = 0.022).
      The expression of the remaining three miRNAs showed no obvious relationship to
      any of the clinicopathological features. The partial response rates of the
      patients with high miRNA1 expression and low miRNA1 expression were 11.1% and
      23.1%, respectively (P = 0.048). Similar results were observed for miRNA27a (the
      partial response rate was 7.7% vs. 25.9%, P = 0.018). Patients with up-regulated
      miRNA27a expression had a significantly worse overall survival (OS) than patients
      with lower miRNA27a expression (P = 0.024). In patients with MRGC, miRNA27a is a
      potential biomarker for predicting resistance to fluoropyrimidine-based
      chemotherapy and a novel prognostic marker for gastric cancer.

PMID- 24122959
TI  - Leg muscle function and fatigue during walking in spinal muscular atrophy type 3.
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) causes muscle weakness and fatigue.
      Better understanding of the relationship between weakness and fatigue may help
      identify potential targets for rehabilitation. METHODS: Gait and surface
      electromyography (EMG) from 4 muscle groups were measured during the Six-Minute
      Walk Test (6MWT) in 10 ambulatory participants, aged 9-49 years. Average root
      mean square amplitude (RMS) of muscle activity was calculated. Strength was
      assessed using manual and quantitative methods. RESULTS: RMS, stride length, and
      velocity decreased during the 6MWT. Knee flexor and hip abductor strength was
      associated with fatigue-related changes; overall strength correlated with disease
      duration; and leg strength was associated with 6MWT distance. CONCLUSIONS:
      Clinical measures are valid in assessing fatigue and function in SMA, and these
      assessments can be enhanced by use of gait analysis and EMG. Disease duration and
      strength measures may represent further stratification refinements when enrolling
      patients in clinical trials.

PMID- 24122960
TI  - Current clinical trials of cell-based therapies in cardiac repair: too many
      variables spoil the stem cell broth.

PMID- 24122961
TI  - Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients
      with acute coronary syndrome.
AB  - AIMS: Dual antiplatelet treatment (DAPT) is a cornerstone in the treatment of
      acute coronary syndrome (ACS) but the optimal treatment duration is unclear. We
      aimed to evaluate the effect of DAPT duration with clopidogrel and aspirin on the
      recurrence of ischaemic events and bleeding in a large, unselected ACS
      population. METHODS AND RESULTS: We performed a prospective, observational cohort
      study of patients in Sweden (n = 56 440) admitted for ACS, with prescribed DAPT
      and hospitalized between January 2006 and July 2010. Patients were obtained from
      the SWEDEHEART register and data were merged with registers from the National
      Board of Health and Welfare. Depending on dispensed clopidogrel tablets, patients
      were divided into groups based on DAPT duration with clopidogrel and aspirin (3
      months: 84-100 clopidogrel tablets (t); >3 months: >100 t; 6 months: 168-200 t;
      >6 months: >200 t). For the combined primary endpoint, defined as all-cause
      death, stroke, or re-infarction, only patients with an uneventful first 3-month
      period (no death, stroke, re-infarction, bleeding, stent thrombosis, or
      revascularization) were included. The incidence of the primary endpoint was 45
      events per 1000 person-years in the >3 months DAPT group compared with 65 events
      per 1000 person-years in the 3 months DAPT group [adjusted HR 0.84, 95% CI (0.75;
      0.95)]. Bleeding was more common in the >3 months treatment group (adjusted HR
      1.56, 95% CI (1.18; 2.07), but the number of events was small. For >6 vs. 6
      months DAPT, the adjusted HR for the combined endpoint was 0.75 with 95% CI
      (0.59; 0.95). CONCLUSION: In this contemporary, large real-life ACS population,
      DAPT for more than 3 months compared with a shorter duration was associated with
      a lower risk of death, stroke, or re-infarction. TRIAL REGISTRATION:
      Clinicaltrials.gov (NCT01623700).

PMID- 24122962
TI  - Using induced electroosmotic micromixer to enhance the reproducibility of
      chemiluminescence intensity.
AB  - In this study, induced electroosmotic vortex flows were generated using an AC
      electric field by one pair of external electrodes to rapidly mix luminescence
      reagents in a 30 MUL micromixer and enhance the reproducibility of
      chemiluminescence (CL) assays. A solution containing the catalyst reagent
      ferricyanide ions (4 MUL) was pipetted into a reservoir containing luminol to
      produce CL in the presence of hydrogen peroxide. When the added ferricyanide
      aliquot contacted the reservoir solution, the CL began flashing, but rapidly
      diminished as the ferricyanide was consumed. In such a short illumination period,
      the solutes could not mix homogeneously. Therefore, the reproducibility of CL
      intensities collected using a CCD and multiple aliquot additions was determined
      to be inadequate. By contrast, when the solutes were efficiently mixed after
      adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was
      significantly improved. When the CL temporal profile was analyzed using a PMT, a
      consistent improvement in reproducibility was observed between the CL intensity
      and estimated CL reaction rate. Replicating the proposed device would create a
      multiple well plate that contains a micromixer in each reservoir; this system is
      compatible with conventional CL instrumentation and requires no CL enhancer to
      slow a reaction. 

PMID- 24122963
TI  - Local and global spatio-temporal dynamics of HIV-1 subtype F1.
AB  - Previous studies have attempted to explore the origin of the F1 subtype, but the
      precise origin of the Romanian and South American F1 variants remains
      controversial. As the F1 subtype is the most frequent non-B variant among
      Europeans residing in Italy, the aim of this study was to estimate its
      phylogeography in order to reconstruct its origin and route of dispersion. The
      phylogeographical analyses, which were made using the Bayesian Markov Chain Monte
      Carlo approach and BEAST software, revealed two significant clades: the first
      included all of the Romanian strains together with a few Italian and four African
      isolates; the second encompassed all of the South American sequences and the
      large majority of Italian variants. By putting the African reference sequences
      into two discrete groups based on specific countries, phylogeographic analysis
      indicated that the F1 epidemic originated in Cameroon/Democratic Republic of
      Congo in the early 1940s, and was exported to South America 10 years later.
      Subsequently, the F1 virus spread to Angola and, from there, was exported to
      Romania in the early 1960s. It reached Italy in the 1970s from South America and
      Romania. The South American and Romanian variants of F1 have different African
      countries of origin and different temporal spreads. The South American variant
      seems to be characterized by multiple introduction events, whereas the Romanian
      strain probably spread as a result of a single entry. Two different pathways from
      South America and Romania led the F1 variant to Italy in the 1970s.

PMID- 24122964
TI  - Differential gene expression of the key signalling pathway in para-carcinoma,
      carcinoma and relapse human pancreatic cancer.
AB  - Pancreatic cancer (PC) has a high rate of mortality and a poorly understood
      mechanism of progression. Investigation of the molecular mechanism of PC and
      exploration of the specific markers for early diagnosis and specific targets of
      therapy are key points to prevent and treat PC effectively and to improve their
      prognosis. In our study, expression profiles experiment of para-carcinoma,
      carcinoma and relapse human PC was performed using Agilent human whole genomic
      oligonucleotide microarrays with 45 000 probes. Differentially expressed genes
      related with PC were screened and analysed further by Gene Ontology term analysis
      and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed
      that there were 3853 differentially expressed genes associated with pancreatic
      carcinogenesis and relapse. In addition, our study found that PC was related to
      the Jak-STAT signalling pathway, PPAR signalling pathway and Calcium signalling
      pathway, indicating their potential roles in pancreatic carcinogenesis and
      progress.

PMID- 24122965
TI  - Synovial osteochondromatosis in the subacromial bursa mimicking calcific
      tendinitis: sonographic diagnosis.
AB  - Synovial osteochondromatosis is an idiopathic benign metaplasia of the synovial
      membrane rarely found in an extra-articular bursa. We describe the case of a 55
      year-old woman with synovial osteochondromatosis in the subacromial bursa
      mimicking calcific tendinitis. Plain radiographs showed a radiopaque mass over
      the middle facet of the greater tuberosity, suggesting calcific tendinitis.
      Sonography, however, showed a loose body in the subacromial bursa, and no
      evidence of calcification inside the rotator cuff.

PMID- 24122966
TI  - Is sex an independent prognostic factor in cutaneous head and neck melanoma?
AB  - OBJECTIVES/HYPOTHESIS: To determine if sex independently affects disease-specific
      survival (DSS) in patients with cutaneous head and neck melanoma. STUDY DESIGN:
      Retrospective analysis of a large population database. METHODS: Our study
      included patients in the Surveillance, Epidemiology, and End Results database
      with cutaneous head and neck melanoma diagnosed from 2004 to 2009. Any cases with
      a history of previous malignancy or with multiple primaries were excluded. We
      obtained data on stage, race, age at diagnosis, radiological treatment status,
      and surgical treatment status. Our analysis consisted of a Kaplan-Meier analysis
      of DSS by sex [correction made here after initial online publication] that was
      supported by a multivariate Cox regression of all significant variables studied.
      RESULTS: There were 13,507 patients identified with cutaneous head and neck
      melanoma who were diagnosed between 2004 and 2009. We observed that female
      patients had a better prognosis than their male counterparts, with 5-year DSS of
      90.40% (95% confidence interval [CI], 89.03%-91.72%) and 87.10% (95% CI, 86.12%
      88.08%), respectively. Multivariable analysis demonstrated a statistically
      significant decrease in disease-specific hazard ratio due to female sex
      independent of stage, treatment, age, or race. CONCLUSIONS: Our study concludes
      that female sex is an independent prognostic factor for cutaneous head and neck
      melanoma. We demonstrated better 5-year DSS in female compared to male patients.
      Better prognosis could be due to multiple factors including differing hair,
      levels of sun exposure, and advanced male age. LEVEL OF EVIDENCE: 2b.

PMID- 24122968
TI  - Refinement of the application of the GROMOS 54A7 force field to beta-peptides.
AB  - In this study, a hexa-beta-peptide whose conformational equilibrium encompasses
      two different helical folds, a right-handed 2.7(10/12)-helix and a left-handed
      3(14)-helix, is simulated using different GROMOS force-field parameter sets. When
      applying the recently developed GROMOS 54A7 force field, a significant
      destabilization effect on the 2.7(10/12)-helix of the peptide is observed, and
      the agreement with the experimental NOE distance bounds is much worse compared
      with the ones using previous versions of the GROMOS force field. This led us to
      investigate the free enthalpy difference between the two helices as a function of
      a variation of different subsets of force-field parameters. Both long time
      molecular dynamics simulations and one-step perturbation predictions suggest that
      the disagreement with the experimental NMR data when using the 54A7 force field
      is caused by the use for beta-peptides of the new backbone phi-/psi-torsional
      angle energy terms introduced in this force field which were based on
      conformational fitting of backbone phi/psi angles for a large set of proteins.
      This means that these parameters of backbone phi- and psi-torsional-angle terms
      should not be applied to non-alpha-peptides such as beta-peptides. This modified
      assignment of torsional-angle energy terms and parameters is denoted as
      54A7_beta. It corrects the wrong description of the conformational ensemble of
      the hexa-beta-peptide obtained using the previous assignment and yields as good
      agreement with NMR data for other beta-peptides that adopt a single helical or a
      hairpin fold.

PMID- 24122967
TI  - Viscous energy loss in the presence of abnormal aortic flow.
AB  - PURPOSE: To present a theoretical basis for noninvasively characterizing in vivo
      fluid-mechanical energy losses and to apply it in a pilot study of patients known
      to express abnormal aortic flow patterns. METHODS: Four-dimensional flow MRI was
      used to characterize laminar viscous energy losses in the aorta of normal
      controls (n = 12, age = 37 +/- 10 yr), patients with aortic dilation (n = 16, age
      = 52 +/- 8 yr), and patients with aortic valve stenosis matched for age and
      aortic size (n = 14, age = 46 +/- 15 yr), using a relationship between the three
      dimensional velocity field and viscous energy dissipation. RESULTS: Viscous
      energy loss was elevated significantly in the thoracic aorta in patients with
      dilated aorta (3.6 +/- 1.3 mW, P = 0.024) and patients with aortic stenosis (14.3
      +/- 8.2 mW, P < 0.001) compared with healthy volunteers (2.3 +/- 0.9 mW). The
      same pattern of significant differences was seen in the ascending aorta, where
      viscous energy losses in patients with dilated aortas (2.2 +/- 1.1 mW, P = 0.021)
      and patients with aortic stenosis (10.9 +/- 6.8 mW, P < 0.001) were elevated
      compared with healthy volunteers (1.2 +/- 0.6 mW). CONCLUSION: This technique
      provides a capability to quantify the contribution of abnormal laminar blood flow
      to increased ventricular afterload. In this pilot study, viscous energy loss in
      patient cohorts was significantly elevated and indicates that cardiac afterload
      is increased due to abnormal flow.

PMID- 24122969
TI  - The role of water and mineral-collagen interfacial bonding on microdamage
      progression in bone.
AB  - Microdamage would be accumulated in bone due to high-intensity training or even
      normal daily activity, which may consequently cause fragility fracture or stress
      fracture. On the other hand, microdamage formation serves as a toughening
      mechanism in bone. However, the mechanisms that control microdamage initiation
      and accumulation in bone are still poorly understood. Our previous finite element
      model indicated that different interfacial properties between mineral and
      collagen in bone may lead to distinct patterns of microdamage accumulation.
      Therefore, the current study was designed to examine such prediction and to
      investigate the role of water and mineral-collagen interactions on microdamage
      accumulation in bone. To address these issues, 48 mice femurs were divided
      randomly into four groups. These groups were dehydrated or treated with
      perfluorotripropylamine (PFTA) or NaF solution to change water distribution and
      mineral-collagen interfacial bonding in bone. After three-point bending fatigue
      tests, the types of microdamage (i.e., linear microcracks or diffuse damage)
      formed in bone were compared between different groups. The results suggested that
      (1) bone tissues with strong mineral-collagen interfacial bonding facilitate the
      formation of linear microcraks, and (2) water has little contribution to the
      growth of microcracks.

PMID- 24122970
TI  - Effects of exposure to extremely low frequency magnetic fields on spermatogenesis
      in adult rats.
AB  - The constant exposure of modern society to extremely low frequency magnetic
      fields (ELF-MF) has raised considerable concerns about the potential risks to
      male reproduction. However, the epidemiological and experimental data remain
      contradictory and inconclusive. In the present study, we investigated the effects
      of 50 Hz ELF-MF of 500 uT applied 4 h/day, 7 days/week for 4 and 8 weeks on male
      reproduction, focusing on changes in spermatogenesis. Several biological
      endpoints related to testicular function and spermatogenesis were measured,
      including the following: body mass, masses of testes and epididymis, sperm count
      and abnormal sperm ratio in the caudal epididymis, serum testosterone level,
      testicular histology, frequency of 14 stages of the cycle of the seminiferous
      epithelium and of four stages of meiosis I, germ cell apoptosis and testicular
      oxidative status. No significant differences were found in the biological
      endpoints between the sham control and the exposed rats in either the 4- or 8
      week exposure period. These negative results may result from the lack of change
      in serum testosterone. In conclusion, our study indicates that exposure to low
      intensity ELF-MF may have no adverse effects on spermatogenesis.

PMID- 24122971
TI  - Viral infection and focal cortical dysplasia.

PMID- 24122973
TI  - Mass-selected IR-VUV (118 nm) spectroscopic studies of radicals, aliphatic
      molecules, and their clusters.
AB  - Mass-selected IR plus UV/VUV spectroscopy and mass spectrometry have been coupled
      into a powerful technique to investigate chemical, physical, structural, and
      electronic properties of radicals, molecules, and clusters. Advantages of the use
      of vacuum ultraviolet (VUV) radiation to create ions for mass spectrometry are
      its application to nearly all compounds with ionization potentials below the
      energy of a single VUV photon, its circumventing the requirement of UV
      chromophore group, its inability to ionize background gases, and its greatly
      reduced fragmenting capabilities. In this review, mass-selected IR plus VUV (118
      nm) spectroscopy is introduced first in a general manner. Selected application
      examples of this spectroscopy are presented, which include the detections and
      structural analysis of radicals, molecules, and molecular clusters in a
      supersonic jet.

PMID- 24122975
TI  - Reply: To PMID 23873583.

PMID- 24122976
TI  - Assessing predictive uncertainty in comparative toxicity potentials of triazoles.
AB  - Comparative toxicity potentials (CTPs) quantify the potential ecotoxicological
      impacts of chemicals per unit of emission. They are the product of a substance's
      environmental fate, exposure, and hazardous concentration. When empirical data
      are lacking, substance properties can be predicted. The goal of the present study
      was to assess the influence of predictive uncertainty in substance property
      predictions on the CTPs of triazoles. Physicochemical and toxic properties were
      predicted with quantitative structure-activity relationships (QSARs), and
      uncertainty in the predictions was quantified with use of the data underlying the
      QSARs. Degradation half-lives were based on a probability distribution
      representing experimental half-lives of triazoles. Uncertainty related to the
      species' sample size that was present in the prediction of the hazardous aquatic
      concentration was also included. All parameter uncertainties were treated as
      probability distributions, and propagated by Monte Carlo simulations. The 90%
      confidence interval of the CTPs typically spanned nearly 4 orders of magnitude.
      The CTP uncertainty was mainly determined by uncertainty in soil sorption and
      soil degradation rates, together with the small number of species sampled. In
      contrast, uncertainty in species-specific toxicity predictions contributed
      relatively little. The findings imply that the reliability of CTP predictions for
      the chemicals studied can be improved particularly by including experimental data
      for soil sorption and soil degradation, and by developing toxicity QSARs for more
      species.

PMID- 24122977
TI  - Epidermal growth factor receptor (EGFR)-targeted therapies in esophagogastric
      cancer.
AB  - Esophageal and gastric cancer incidence has been increasing worldwide. Most cases
      are diagnosed in advanced stages, and current therapy has not been able to
      improve the modest survival rates after diagnosis. Epidermal growth factor
      receptor expression has been found to correlate with poor prognosis and
      aggressive disease in esophagogastric cancers. Targeting these receptors through
      monoclonal antibody or downstream inhibition of tyrosine kinase has produced some
      encouraging results. The Trastuzumab for Gastric Cancer (ToGA) trial demonstrated
      that trastuzumab, a monoclonal antibody directed against the Her-2 receptor
      improves survival in Her-2 positive advanced gastric and gastro-esophageal
      cancers. Encouraging results have been reported in the ongoing clinical trials of
      EGFR-directed therapies in combination with concurrent chemoradiation for the
      locally advanced esophagogastric cancers. Identification of pertinent biomarkers
      of efficacy will likely lead to further optimization of EGFR-directed treatment.
      In the current article, we will be discussing the mechanisms of action, completed
      phase II/III trials and future of epidermal growth factor targeted-therapy in
      gastric and esophageal cancers.

PMID- 24122978
TI  - Overcoming platinum drug resistance with copper-lowering agents.
AB  - Platinum (Pt)-based antitumor agents have been the mainstay of cancer
      chemotherapy for the last three decades. While multiple mechanisms are
      responsible for treatment failure, deficiency in drug transport is an important
      contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also
      transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced
      hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in
      patients who failed chemotherapy with these drugs. We previously demonstrated
      that Cu chelation induces the expression of transcription factor Sp1 which binds
      the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas
      Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their
      promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated
      within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated
      manner. These findings suggest that it is feasible to module cDDP transport
      capacity through intervention of mammalian Cu homeostasis. Indeed, we found that
      cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1
      expression by up-regulation of Sp1 in cultured cells. This discovery provided a
      mechanistic basis for the ongoing clinical study using Cu chelator to overcome
      cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper
      chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5
      ovarian cancer patients showed encouraging results. This short review describes
      the perspectives of using Cu-lowering agents in overcoming Pt resistance in
      cancer chemotherapy.

PMID- 24122980
TI  - Musculoskeletal sarcomas in the forearm and hand: standard treatment and
      microsurgical reconstruction for limb salvage.
AB  - Sarcomas in the forearm and hand are very rare, accounting for less than 1% of
      all upper-limb tumors and clinical outcomes after surgery and adjuvant therapies
      are uncertain. The forearm and hand present specific challenges due to their
      unique anatomical structures. There is little soft tissue and each compartment is
      narrow, such important structures exist in close proximity. Anatomic constraints
      make it difficult to achieve wide surgical margins. Although sarcomas often
      metastasize to the lung, the overall survival rate is excellent. Wide marginal
      resection during initial surgery is the most predictive factor for tumor control.
      The role of reconstructive surgery following wide excision for sarcoma of the
      forearm and hand is even more important than elsewhere in the body because
      excision is likely to cause bone, tendon and nerve defects, leading to severe
      functional deficits. Multiple options exist for bony and soft tissue
      reconstruction of the upper limb, with the choice dependent upon tumor type,
      wound characteristics, surgeon preference and the patients' functional
      requirements. Success should be measured not just by stable wound coverage but
      also by preservation of patient's health, limb cosmesis, sensation and function.
      Careful preoperative planning with consideration of all the possible resected
      structures should improve patient outcomes. 

PMID- 24122979
TI  - Chemoprevention of prostate cancer by major dietary phytochemicals.
AB  - Prostate cancer continues to be one of the most commonly diagnosed diseases and
      the second leading cause of cancer-related deaths among men in the United States.
      Options exist to treat localized disease, including surgery, radiation therapy,
      and hormonal therapy, but clinical management of advanced prostate cancer is
      challenging. In the past few decades, chemoprevention involving naturally
      occurring compounds has emerged as a promising and cost-effective approach to
      reduce incidence and morbidity of prostate cancer by inhibiting the precancerous
      events before the occurrence of clinical disease. The present review focuses on
      summarizing the recent advances in studies of major dietary phytochemicals and
      their role in prostate cancer development. 

PMID- 24122981
TI  - Saving ears and kidneys from cisplatin.
AB  - Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute
      and chronic nephro-, oto-, and also peripheral neuro-toxicity. Since transporters
      are important mediators of specific cellular uptake of many drugs such as
      cisplatin, their role as possible targets of specific organ protection against
      undesired cisplatin toxicities is under investigation. Several transporters are
      able to mediate the movement of cisplatin across the plasma membranes: Copper
      transporter-1 (Ctr1), copper transporter-2 (Ctr2), P-type copper-transporting
      ATPases ATP7A and ATP7B, organic cation transporter-2 (OCT2), and multidrug
      extrusion transporter-1 (MATE1). Some of these transporters are also able to
      accept other platinum derivatives as substrates. In the present review article,
      we focus on the role of Ctr1 and OCT2 for cellular uptake of cisplatin and on the
      possibilities to reduce cisplatin-associated toxicities decreasing cisplatin
      uptake mediated by these transporters. The ubiquitously expressed Ctr1 seems to
      be involved in general cisplatin uptake in tumor and normal cells. Conversely,
      OCT2 expression is restricted to few cells such as renal, cochlear, and nervous
      cells, while its expression in some tumors seems to be epigenetically down
      regulated. For this reason, specific inhibition of OCT2 may be effective in
      decreasing cisplatin uptake in non-target cells, without compromising its anti
      tumoral efficacy, and therefore OCT2 may be the target for a suitable protective
      therapy.

PMID- 24122982
TI  - Antigen-specific in vitro expansion of functional redirected NY-ESO-1-specific
      human CD8+ T-cells in a cell-free system.
AB  - BACKGROUND: Tumors can be targeted by the adoptive transfer of chimeric antigen
      receptor (CAR) redirected T-cells. Antigen-specific expansion protocols are
      needed to generate large quantities of redirected T-cells. We aimed to establish
      a protocol to expand functional active NY-ESO-1-specific redirected human CD8(+)
      T-cells. MATERIALS AND METHODS: The anti-idiotypic Fab antibody A4 with
      specificity for HLA-A 0201/NY-ESO-1157-165 was tested by competition assays using
      a HLA-A 0201/NY-ESO-1157-165 tetramer. HLA-A 0201/NY-ESO-1157-165 redirected T
      cells were generated, expanded and tested for CAR expression, cytokine release,
      in vitro cytolysis and protection against xenografted HLA-A 0201/NY-ESO-1157-165
      positive multiple myeloma cells. RESULTS: A4 demonstrated antigen-specific
      binding to HLA-A 0201/NY-ESO-1157-165 redirected T-cells. Expansion with A4
      resulted in 98% of HLA-A 0201/NY-ESO-1157-165 redirected T-cells. A4 induced
      strong proliferation, resulting in a 300-fold increase of redirected T-cells.
      After expansion protocols, redirected T-cells secreted Interleukin-2, (IL-2),
      interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) and lysed
      target cells in vitro and were protective in vivo. CONCLUSION: A4 expanded HLA-A
      0201/NY-ESO-1157-165 redirected T-cells with preservation of antigen-specific
      function.

PMID- 24122984
TI  - A novel mouse model of metastatic thyroid carcinoma using human adipose tissue
      derived stromal/stem cells.
AB  - BACKGROUND/AIM: Scientists have been in quest for the best in vivo model to
      evaluate chemotherapies for radioiodine-resistant metastatic thyroid carcinomas.
      Human adipose tissue-derived stromal/stem cells (ASCs) have been found to promote
      in vitro growth and in vivo tumorigenesis. In the present study, we describe a
      novel model of metastatic human thyroid carcinoma by combining ASCs with the
      papillary thyroid cancer, K1 cell line. MATERIALS AND METHODS: Three groups of
      severe combined immunodefecient mice were investigated. The first group was
      injected subcutaneously with K1 cells plus ASCs, the second group with K1 cell
      only, and the last group with ASCs only. Mean tumor volumes and standard
      deviations were calculated and compared. RESULTS: Concomitant injection of ASCs
      with the K1 cell line led to the development of significantly larger tumors
      compared to the other groups (p<0.05). In addition, the lungs of this group
      demonstrated gross tumor metastasis and pathological features of high-grade
      neoplasms. CONCLUSION: In the present study we describe a novel mouse model using
      ASCs with the potential to be used for assessment of new treatments for the
      management of metastatic thyroid carcinomas.

PMID- 24122983
TI  - Immunohistochemical quantification of the vitamin B12 transport protein (TCII),
      cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts.
AB  - BACKGROUND/AIM: Cancer cells have an essential demand for vitamin B12 (cobalamin)
      to enable cellular replication. The present pilot study quantified the
      immunohistochemical expression of vitamin B12 transport protein (Transcobalamin
      II; TCII), cell surface receptor (Transcobalamin II-R; TCII-R) and proliferation
      protein (Ki-67) in human tumor xenografts. MATERIALS AND METHODS: Tissue
      microarray slides containing 34 xenograft tumor tissues were
      immunohistochemically stained using TCN2 (anti-TCII), CD320 (anti-TCII-R) and MIB
      1 (anti-Ki-67) antibodies. Representatively stained areas of all slides were
      digitally imaged and protein expression was quantified using ImageJ software
      plugins. RESULTS: All xenograft tumor tissues stained positively for TCII, TCII-R
      and Ki-67 proteins; expression varied both within and between tumor types.
      Correlation between TCII/TCII-R and Ki-67 expression was not significant in
      xenograft tissues. CONCLUSION: Proliferating cancer cells express measurable
      levels of TCII and TCII-R. Immunohistochemical quantification of these markers
      may be useful as a tool for detection of tumors, tailored selection of anti-tumor
      therapies and surveillance for evidence of recurrent disease.

PMID- 24122985
TI  - Biological correlation of 18F-FDG uptake on PET in pulmonary neuroendocrine
      tumors.
AB  - BACKGROUND: It is widely recognized that pulmonary neuroendocrine tumors (PNET)
      include a spectrum that ranges from low-grade typical carcinoid (TC) and atypical
      carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and
      small cell lung carcinoma (SCLC). However, little is known about the usefulness
      of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron-emission tomography
      (PET) in such tumors. We therefore, conducted a study including the analysis of
      the underlying biology of (18)F-FDG uptake. MATERIALS AND METHODS: Thirty-four
      patients with early-stage PNETs who underwent (18)F-FDG PET before treatment were
      included in this study. Tumor sections were stained by immunohistochemistry for
      glucose transporter-1 (Glut1 and Glut3), hypoxia-inducible factor-1 alpha (HIF
      1alpha), hexokinase-I, vascular endothelial growth factor (VEGF), microvessel
      density (MVD) determined by CD34 and (Akt)/mammalian target of rapamycin (mTOR)
      signaling pathway. RESULTS: (18)F-FDG uptake correlated significantly with Glut1,
      HIF-1alpha, VEGF and CD34 expression. Uptake of (18)F-FDG tended to increase from
      low-grade to high-grade PNETs. Tumor metabolic activity was a useful marker for
      predicting postoperative prognosis in patients with early-stage PNETs.
      CONCLUSION: The amount of (18)F-FDG uptake is determined by the presence of
      glucose metabolism, hypoxia and angiogenesis.

PMID- 24122986
TI  - Imaging nuclear - cytoplasm dynamics of cancer cells in the intravascular niche
      of live mice.
AB  - We have previously shown that cancer cells can form an intravascular niche where
      they can proliferate and undergo apoptosis as well as traffic and extravasate. In
      the present study, green fluorescent protein (GFP) was expressed in the cytoplasm
      of HT-1080 human fibrosarcoma cells, and red fluorescent protein (mCherry),
      linked to histone H2B, was expressed in the nucleus to further investigate
      intravascular cancer cell nuclear-cytoplasmic dynamics. Nuclear mCherry
      expression enabled visualization of nuclear dynamics, whereas simultaneous
      cytoplasmic GFP expression enabled visualization of nuclear-cytoplasmic ratios as
      well as simultaneous cell and nuclear deformation. Cancer cells were injected in
      the epigastric cranialis vein in an abdominal flap of nude mice to enable
      subcellular in vivo imaging. The cell cycle position of individual living cells
      was readily-visualized by the nuclear-cytoplasmic ratio and nuclear morphology.
      Real-time induction of apoptosis was observed by nuclear size changes and
      progressive nuclear fragmentation. Intra- and extra-vascular mitotic cells were
      visualized by imaging. One hour after cell injection, round and elongated cancer
      cells were observed in the vessels. Three hours after injection, invadopodia-like
      structures of the cancer cells were observed. Five hours after injection, dual
      color cancer cells began to divide within the vessel. By 10 h, some intravascular
      cancer cells underwent apoptosis. Deformed new blood vessels in the tumor were
      observed 10 days later. Extravascular cancer cells were imaged dividing in the
      tumor at day 14 after injection. The subcellular in vivo imaging approach
      described in the present report provides new visual targets for trafficking and
      proliferating intravascular cancer cells as well as extravasating and invading
      cancer cells.

PMID- 24122987
TI  - Therapy with siRNA for Vegf-c but not for Vegf-d suppresses wide-spectrum organ
      metastasis in an immunocompetent xenograft model of metastatic mammary cancer.
AB  - Cancer metastasis contributes significantly to cancer mortality and is
      facilitated by lymphangiogenesis and angiogenesis. Vascular endothelial growth
      factors-C and D (VEGF-C and VEGF-D) are heavily involved in lymphangiogenesis.
      Using small interfering RNA (siRNA) against mouse Vegf-c, and Vegf-d, we sought
      to inhibit metastasis in a model of metastatic murine mammary cancer.
      BJMC3879Luc2 cell-induced mammary carcinomas received direct intratumoral
      injections in vivo of either plasmid VEGF-C/D siRNA (psiVEGF-C, psiVEGF-D) or a
      vector control followed by in vivo gene electrotransfer weekly for seven weeks.
      Treatment with psiVEGF-C and with psiVEGF-D resulted in lower tumor volumes as
      compared to the controls. Treatment with psiVEGF-C suppressed wide-spectrum organ
      metastasis involving lung and lymph nodes. Treatment with psiVEGF-C further
      reduced the number of dilated lymphatic vessels with invading cancer cells and
      inhibited tumor blood microvessel density. In contrast, although treatment with
      psiVEGF-D was not effective and gave equivocal results, it did induce some
      insignificant reduction in tumor volume increment, average numbers of lymph node
      metastases and average number of intratumoral dilated lymphatic vessels. In
      conclusion, specific silencing of the Vegf-c gene suppresses wide-spectrum organ
      metastasis, including the lung and lymph nodes. However, therapy with siRNA for
      Vegf-d was not adequately effective in this murine system.

PMID- 24122988
TI  - Prevention of carboplatin-induced resistance in human ovarian tumor xenografts by
      selenite.
AB  - BACKGROUND/AIM: We have been exploring a prevention approach to the problem of
      drug resistance which develops during ovarian cancer chemotherapy. We have
      previously described an in vivo model of the development of resistance to the
      chemotherapy drug cisplatin in xenografts, and the prevention of this resistance
      by selenium compounds. However, a different platinum-based drug, carboplatin, is
      frequently utilized in ovarian cancer treatment. The aim of the present study was
      to design a model for the induction of resistance by carboplatin in vivo.
      MATERIALS AND METHODS: Tumors were initiated in immunodeficient mice by
      subcutaneous inoculation of A2780 human ovarian tumor cells. The sensitivity of
      the resulting tumors to therapy was determined by measuring the effect on tumor
      growth of a single intraperitoneal (i.p.) treatment with a high dose of
      carboplatin. RESULTS: The growth of control tumors was completely (although
      temporarily) stopped by this treatment; however, a single pre-treatment with a
      low i.p. dose of carboplatin resulted in the rapid development of resistance to
      carboplatin, and cross-resistance to cisplatin. Pre-treatment with selenite in
      addition to carboplatin prevented the induction of resistance. When cells from
      these pre-treated tumors were transplanted to new animals, the derivative tumors
      retained the sensitive or resistant phenotype of their tumor of origin.
      CONCLUSION: Selenite can prevent the induction of resistance by carboplatin in
      human ovarian tumors, and thus may offer an approach to extending the long-term
      efficacy of platinum chemotherapy.

PMID- 24122989
TI  - Effects of sevoflurane on breast cancer cell function in vitro.
AB  - Some retrospective clinical studies have shown there to be an an association
      between the anaesthetic technique employed during breast cancer surgery and
      recurrence or metastases. Little is known about the direct effects of volatile
      anaesthetics on cancer cells. In the present study we investigated the effects of
      sevoflurane on estrogen receptor-positive (ER(+)) and estrogen receptor-negative
      (ER(-)) breast cancer cell functions that may contribute to metastatic potential.
      MATERIALS AND METHODS: MCF7 ER(+) and MDA-MB-231 ER(-) breast cancer cells were
      incubated with or without sevoflurane, at concentrations of 1, 2, 3, and 4 mM for
      6 h. Cell proliferation migration and invasion assays were then employed to
      measure for sevoflurane effects. An independent sample t-test analysis was used
      to compare for differences obtained between the groups. RESULTS: Sevoflurane
      increased proliferation in MCF7 cells by 50-63% and by 50-67% in MDA-MB-231 cells
      (p<0.05). Sevoflurane increased migration in both breast cancer cell lines, by 30
      58% in MCF7 (p=0.04) and by 30-230% in MDA-MB-231; statistically significant at
      2, 3 and 4 mM (p<0.03). Increase in invasion ranged from 100-170% in MCF7,
      (p=0.02) and 28-72% in the MDA-MB-231 cell line, statistically significant only
      at the 4-mM concentration. CONCLUSION: In this in vitro model of breast cancer
      cell function, sevoflurane increased proliferation, migration and invasion in ER
      positive MCF7 cells and increased proliferation, and migration but not invasion
      in ER-negative cells. However, the observed effect size was small and not dose
      dependent.

PMID- 24122990
TI  - Expression of high mobility group A proteins in oral leukoplakia.
AB  - BACKGROUND: Oral leukoplakia (LPL) is considered a potentially malignant disorder
      in the oral cavity and the gastric tract. High mobility group A (HMGA) proteins
      are important in the transformation of normal cells into cancer cells, but there
      is a lack of knowledge on their importance in oral cancer development. The aim of
      the current project was to investigate HMGA expression in LPLs with different
      levels of dysplasia. MATERIALS AND METHODS: Biopsies were histologically
      processed to visualize the expression of HMGA1 and HMGA2 using
      immunohistochemistry. RESULTS: An increase of HMGA1-positive cells correlating to
      the degree of dysplasia was registered in the epithelium and in the connective
      tissue. HMGA2 expression was seen in the epithelium and in the connective tissue
      but with no obvious correlation to the level of dysplasia. CONCLUSION: This is,
      to our knowledge, the first study showing the expression of HMGA proteins in
      healthy and non-healthy oral mucosa.

PMID- 24122991
TI  - Fully-automated radiosynthesis and in vitro uptake investigation of [N-methyl
      11C]methylene blue.
AB  - Malignant melanoma is a type of skin cancer which can spread rapidly if not
      detected early and left untreated. Positron Emission Tomography (PET) is a
      powerful imaging technique for detecting cancer but with only a limited number of
      radiotracers available the development of novel PET probes for detection and
      prevention of cancer is imperative. In the present study we present the fully
      automated radiosynthesis of [N-methyl-(11)C]methylene blue and an in vitro uptake
      study in metastasic melanoma cell lines. Using the GE TRACERlab FXc Pro module [N
      methyl-(11)C]methylene blue was isolated via solid-phase extraction in an average
      time of 36 min after end of bombardment and formulated with a radiochemical
      purity greater than 95%. The in vitro uptake study of [N-methyl-(11)C]methylene
      blue in SK-MEL28 melanin-expressing melanoma cell line demonstrated in site
      specific binding of 51% promoting it as a promising melanoma PET imaging agent.

PMID- 24122992
TI  - Id4 promotes senescence and sensitivity to doxorubicin-induced apoptosis in DU145
      prostate cancer cells.
AB  - Inhibitor of differentiation proteins (Id1, 2, 3 and 4) are dominant negative
      regulators of basic helix loop helix transcription factors and play dominant
      roles in cancer cells, spanning several molecular pathways including senescence,
      invasion, metastasis, proliferation and apoptosis. In contrast to high Id1, Id2
      and Id3 expression, the expression of Id4 is epigenetically silenced in prostate
      cancer. In the present study we demonstrated a novel role of Id4, that of
      promotion of cellular senescence in prostate cancer cells. MATERIALS AND METHODS:
      Id4 was ectopically expressed in DU145 cells (DU145+Id4). The cells treated with
      Doxorubicin (0-500 nm) or vehicle control were analyzed for apoptosis, senescence
      (SA-beta Galactosidase), and expression of CDKN1A (p21), CDKN1B(p27), CDKN2A
      (p16), E2F1, vimentin and E-cadherin by immuno-histochemistry and/or Western
      blot. RESULTS: In the present study we demonstrated that Id4 promotes cellular
      senescence in prostate cancer cell line DU145. Ectopic overexpression of Id4 in
      androgen receptor-negative DU145 prostate cancer cells resulted in increased
      expression of p16, p21, p27, E-cadherin and vimentin but down-regulated E2F1
      expression. Id4 also potentiated the effect of doxorubicin induced senescence and
      apoptosis. CONCLUSION: The absence of functional p16, pRB and p53 in DU145
      suggests that Id4 could alter additional molecular pathways such as those
      involving E2F1 to promote senescence and increased sensitivity to doxorubicin
      induced apoptosis. The results of the present study support the role of Id4 as a
      tumor suppressor in prostate cancer.

PMID- 24122993
TI  - Ursolic acid inhibits the growth of colon cancer-initiating cells by targeting
      STAT3.
AB  - BACKGROUND: We have previously reported Signal Transducer and Activator of
      Transcription 3 (STAT3) to be constitutively activated in aldehyde dehydrogenase
      (ALDH)(+)/cluster of differentiation-133 (CD133)(+) colon cancer-initiating
      cells. In the present study we tested the efficacy of inhibiting STAT3 signaling
      in human colon cancer-initiating cells by ursolic acid (UA), which exists widely
      in fruits and herbs. RESULTS: Our data demonstrated that UA inhibited STAT3
      phosphorylation, and induced caspase-3 cleavage of ALDH(+)/CD133(+) colon cancer
      initiating cells. UA also reduced cell viability and inhibited tumor sphere
      formation of colon cancer-initiating cells, more potently than two other natural
      compounds, resveratrol and capsaicin. UA also inhibited the activation of STAT3
      induced by interleukin-6 in DLD-1 colon cancer cells. Furthermore, daily
      administration of UA suppressed HCT116 tumor growth in mice in vivo. CONCLUSION:
      Our results suggest STAT3 to be a target for colon cancer prevention. UA, a
      dietary agent, might offer an effective approach for colorectal carcinoma
      prevention by inhibiting persistently activated STAT3 in cancer stem cells.

PMID- 24122994
TI  - Development and pharmacokinetic evaluation of a curcumin co-solvent formulation.
AB  - Poor solubility and bioavailability are limiting factors for the clinical
      application of curcumin. The objective of the current study was to develop a
      liquid formulation with increased solubility and systemic bioavailability. A co
      solvent formulation with increased solubility of 20 mg/ml was developed and
      optimized. Pharmacokinetics of the new formulation were evaluated using rats
      receiving 30 mg/kg intravenous or 50 mg/kg intramuscular administration of co
      solvent formulation, compared against a control group receiving 50 mg/kg of
      curcumin in DMSO through intramuscular injection. Plasma concentrations were
      measured using liquid chromatography-mass spectrometry (LC-MS/MS). The
      intramuscular injection of formulation resulted in 30% absolute bioavailability
      and provided sustained release by maintaining plasma concentrations of curcumin
      above 240 ng/ml for up to 4 h. A 29-fold increase in the maximum plasma
      concentration (Cmax) and 28-fold increase in the area under the plasma
      concentration versus time curve (AUC) led to a 28-fold increase in relative
      bioavailability for the co-solvent formulation. The findings reported here
      suggest that the clinical application of curcumin can be better-exploited through
      an intramuscular administration of the co-solvent formulation developed in the
      present study. 

PMID- 24122995
TI  - NOTCH knockdown affects the proliferation and mTOR signaling of leukemia cells.
AB  - AIM: The effects of small interfering RNA (siRNA)-mediated knockdown of NOTCH1
      and NOTCH2 on cell proliferation and downstream signaling pathways in leukemia
      cells were examined. MATERIALS AND METHODS: Two T-lymphoblastic leukemia (T-ALL)
      cell lines and two acute myeloblastic leukemia (AML) cell lines were transfected
      with siRNAs targeting NOTCH1 and NOTCH2. The effects of knockdown on cell
      proliferation and protein expression were examined by colorimetric WST-8 assay
      and immunoblotting, respectively. RESULTS: In T-ALL cell lines, NOTCH1 knockdown
      as well as NOTCH2 knockdown suppressed cell proliferation and induced apoptosis.
      v-Myc avian myelocytomatosis viral oncogene homolog (MYC) protein expression was
      down-regulated in NOTCH1-knockdown cells but not affected in NOTCH2-knockdown
      cells. In AML cell lines, cell proliferation was not significantly affected by
      NOTCH siRNAs. NOTCH2 knockdown increased the level of cleaved NOTCH1 fragment
      without increasing NOTCH1 expression. NOTCH knockdown reduced the level of
      mechanistic target of rapamycin (mTOR) protein in the monoblastic leukemia cell
      line THP-1. Contrastingly, NOTCH activation by NOTCH ligand stimulation increased
      the expression of mTOR in THP-1 cells. CONCLUSION: These novel findings on NOTCH
      signaling may contribute to the development of effective NOTCH-targeted therapies
      against leukemia.

PMID- 24122996
TI  - Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell
      lines and comprehensive gene expression analysis.
AB  - BACKGROUND: Intraperitoneal (i.p.) chemotherapy with paclitaxel is a potential
      therapeutic modality for patients with peritoneal metastasis of gastric cancer.
      To overcome paclitaxel resistance, which is a major clinical problem with this
      modality, prediction of i.p. paclitaxel resistance is critically important.
      MATERIALS AND METHODS: We developed three new i.p. paclitaxel-resistant cell
      lines from parental gastric cancer cell lines by an in vivo selection method
      using i.p. paclitaxel chemotherapy. With these cell lines, we performed gene
      expression profiling analysis to select up-regulated genes in i.p. paclitaxel
      resistant cells and validated the genes with clinical samples. RESULTS: We
      successfully isolated nine up-regulated genes in i.p. paclitaxel-resistant cell
      lines compared with parental cells by microarray analysis, followed by
      confirmation with quantitative reverse transcriptase-polymerase chain reaction
      (qRT-PCR). Among these, we identified four genes, namely kinesin family member-23
      (KIF23), ERBB2 interacting protein (ERBB2IP), ATPase family, AAA domain
      containing-2 (ATAD2) and PHD finger protein (PHF19) as candidate genes for
      paclitaxel resistance after validation with clinical samples derived from
      responders and non-responders to paclitaxel treatment. CONCLUSION: These i.p.
      paclitaxel-resistant cell lines are ideal models for understanding the mechanism
      of resistance to i.p. paclitaxel and development of a new therapeutic modality.
      Four up-regulated genes may be potential new predictive markers for resistance to
      i.p. paclitaxel in patients with peritoneal metastasis of gastric cancer.

PMID- 24122997
TI  - Aberrant expression of EZH2 is associated with pathological findings and P53
      alteration.
AB  - AIM: Enhancer of zeste homolog-2 (EZH2) and B lymphoma Mo-MLV insertion region-1
      homolog (BMI1) are members of the polycomb group of proteins, which function as
      transcriptional repressors through chromatin modification. EZH2 forms part of the
      polycomb repressive complex (PRC)-2, while BMI1 is a component of PRC1. Previous
      studies have shown that EZH2 is highly expressed in various type of cancers.
      Expression of EZH2 is reported to be regulated by the P53-E2F/retinoblastoma (RB)
      related pathway, and a correlation between P53 mutation and EZH2 expression was
      recently found in breast cancer. Here, we examined the relationship between P53
      and EZH2 in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Using
      immunohistochemistry, we investigated the expression of EZH2 and BMI1 in 99
      surgically-resected OSCC and 34 epithelial dysplasia samples. We analyzed
      associations between aberrant expression of EZH2 and BMI1, and
      clinicopathological findings and patient outcome. P53 expression was also
      examined and analyzed in relation to EZH2 and BMI1 expression. RESULTS: EZH2 and
      BMI1 protein were up-regulated in OSCC tissues compared with epithelial dysplasia
      and normal epithelium. Aberrant EZH2 and BMI1 protein expression was observed in
      32 and 59 of the 99 OSCC samples, respectively. Aberrant EZH2 and BMI1 expression
      was significantly associated with mode of invasion, but not with lymph node
      metastasis or survival rate. Aberrant EZH2 expression was associated with P53
      alteration in OSCC tissue. Expression of EZH2 mRNA in SAS/neo cells, which have
      wild-type P53, was significantly lower than in SAS/mp53 cells that have a mutant
      P53 gene. CONCLUSION: P53 alteration may be involved in dysregulated EZH2
      expression, and aberrant expression of EZH2 may play a role in carcinogenesis of
      OSCC.

PMID- 24122998
TI  - Eicosapentaenoic acid modifies cytokine activity and inhibits cell proliferation
      in an oesophageal cancer cell line.
AB  - BACKGROUND/AIM: The present study investigated the effect of eicosapentaenoic
      acid (EPA) on nuclear factor-kappa B (NF-kappaB) activation, inflammatory
      interleukin-6 (IL-6) production, and cell proliferation in a human oesophageal
      carcinoma cell line (TE-1). MATERIALS AND METHODS: Lipopolysaccharide (LPS)
      induced IL-6 production in TE-1 cells in the presence or absence of EPA was
      determined using enzyme-linked immunosorbent assay (ELISA). The proliferation of
      TE-1 cells was determined by the WST-1 assay. TE-1 cells were stained with
      Hoechst 33342 and propidium iodide to observe apoptosis. Immunohistochemical
      staining of NF-kappaB in TE-1 cells was performed. RESULTS: LPS increased IL-6
      production in TE-1 cells, and EPA treatment prevented this effect. EPA treatment
      inhibited NF-kappaB activation and induced apoptosis of TE-1 cells. CONCLUSION:
      EPA inhibits NF-kappaB activation and IL-6 production in oesophageal cancer
      cells, their inducing apoptosis. These effects of EPA may be of benefit in
      improving the outcome of cancer surgery.

PMID- 24122999
TI  - Loss of 5-hydroxymethylcytosine and TET2 in oral squamous cell carcinoma.
AB  - AIM: Epigenetic modifications, such as DNA methylation, are considered important
      in the regulation of target genes in cancer development. 5-Hydroxymethylcytosine
      (5hmC) was recently discovered to be related to the process of malignant
      transformation. The influence of DNA methylation in oral squamous cell carcinomas
      (OSCC) is not fully-understood. Therefore, the aim of the present study was to
      investigate the DNA methylation pattern in OSCC compared to healthy oral
      epithelium. MATERIALS AND METHODS: Oral mucosal samples from patients with OSCC
      (n=15) and healthy mucosa (n=12) were analyzed using immunohistochemistry with
      antibodies against 5hmC, 5mC and ten-eleven-translocation-2 (TET2). RESULTS: A
      significant decrease in 5hmC and TET2 expression was found in OSCC compared to
      healthy oral epithelium. In contrast, there was a significant increase in 5mC
      expression in OSCC compared to healthy epithelium. CONCLUSION: Our results
      indicate that loss of 5hmC is an epigenetic event of OSCC.

PMID- 24123000
TI  - Prognostic significance of p21 expression in patients with esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Although p21 is an important component that regulates cell-cycle
      progression, no consensus has been reached about its clinicopathological
      significance in esophageal squamous cell carcinoma (ESCC). In the present study,
      we investigated its prognostic significance and correlation with cyclin-D1
      (CCND1) expression in ESCC. MATERIALS AND METHODS: The p21 labeling index (LI)
      was calculated by immunohistochemistry for 69 primary tumor samples obtained from
      patients with ESCC who had undergone curative esophagectomy, and correlations
      between p21 LI and various clinicopathological features, prognosis, and CCND1 LI
      were studied. RESULTS: The p21 LI of these tumors ranged from 2.0% to 57.0%
      (median=28.4%, mean+/-SD=27.3% +/- 13.0). p21 LI was positively correlated with
      CCND1 LI. When patients were divided into two groups using a p21 LI cut-off value
      of 30%, the 5-year survival rate of patients with p21 LI of >= 30% was 80.0%,
      which was significantly higher than that of patients with p21 LI of <30% (55.5%).
      Furthermore, when patients were divided into four groups according to p21 and
      CCND1 expression, the 5-year survival rate of patients with p21 LI of <30% and
      CCND1 LI of >= 45% was the lowest (44.4%). Multivariate analysis demonstrated
      that venous invasion, lymphatic invasion, and p21 LI were independent prognostic
      factors. CONCLUSION: Our results indicate that p21 LI is correlated with CCND1 LI
      and can be used as an independent prognostic factor for patients with ESCC
      following selection of a suitable cut-off value.

PMID- 24123001
TI  - Radiation-induced dimer formation of EGFR: implications for the radiosensitizing
      effect of cetuximab.
AB  - AIM: The purpose of this study was to investigate whether radiation induces
      ligand-independent dimerization of epidermal growth factor receptor (EGFR) and
      explore the possible role of radiation-induced receptor dimerization in the
      radiosensitizing effect of cetuximab. MATERIALS AND METHODS: The human vulvar
      squamous cell carcinoma cell line A431 was used. The dimerization and activation
      of EGFR were quantified using immunoprecipitation, a western blotting analysis,
      and a chemical cross-linking analysis with dithiobis-sulfosuccinimidyl
      propionate. RESULTS: Irradiation at a dose of 2 Gy induced the
      autophosphorylation of EGFR. Consistent with autophosphorylation, a 360-kDa
      polypeptide, corresponding to the size of the EGFR dimer, was detected in
      addition to an EGFR monomer. Radiation also induced hetero-dimerization between
      EGFR and HER2/neu. Cetuximab combined with radiation inhibited radiation-induced
      autophosphorylation of EGFR, and inhibited radiation-induced homo-dimerization of
      EGFR. However, cetuximab incompletely inhibited radiation-induced hetero
      dimerization between EGFR and HER2. CONCLUSION: The results of this investigation
      suggest that radiation-induced homo- and/or hetero-dimerization between EGFR
      and/or HER2 might be involved in the radioresponse of cancer cells.

PMID- 24123002
TI  - 7-substituted coumarins inhibit proliferation and migration of laryngeal cancer
      cells in vitro.
AB  - BACKGROUND: Coumarins are a large group of naturally-occurring compounds with a
      wide range of biological properties, including anticancer activity. 7-Substituted
      coumarins (umbelliferone, scoparone, and herniarin) were analyzed for their
      potential anticancer activity against laryngeal cancer cells (LCC). MATERIALS AND
      METHODS: High-performance counter-current chromatography was applied for
      successful separation of umbelliferone from fruits of Heracleum leskowii. A two
      phase solvent system composed of n-heptane-methanol-ethyl acetate-water (1:2:1:2,
      v/v/v) was successfully used. Cell proliferation was assessed after 48-72 h by
      means of MTT test, and tumor cell motility by a wound assay model. Measurement of
      cell death was estimated using enzyme-linked immunosorbent assay (ELISA), and
      cell-cycle analysis was performed by flow cytometry. Extracellular signal
      regulated kinases-1/2 (ERK1/2) and AKT kinase activation status were analyzed by
      western blotting. RESULTS: Umbelliferone, scoparone, and, to a lesser extent,
      herniarin reduced viability and migration of RK33 LCC in a dose-dependent manner.
      Scoparone and herniarin were found to induce apoptosis of LCC. None of the tested
      compounds influenced the ERK1/2 and AKT kinase activity, nor significantly
      affected cell-cycle progression in the LCC line studied. CONCLUSION: Our findings
      suggest the therapeutic potential of 7-substituted coumarins in the treatment of
      laryngeal cancer.

PMID- 24123003
TI  - Differential protein expression of lymph node metastases of papillary thyroid
      carcinoma harboring the BRAF mutation.
AB  - BACKGROUND: The prognostic role of the T1799A BRAF mutation is controversial. We
      investigated the protein expression in papillary thyroid carcinoma (PTCs) samples
      harboring the specific mutation using proteomic tools. MATERIALS AND METHODS: We
      performed two-dimensional gel electrophoresis to identify differential protein
      expression regarding lymph node metastasis (LNM). Proteins were identified by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
      Immunohistochemical staining was performed for 38 PTCs harboring the mutation. We
      validated the association between these proteins and clinicopathological factors
      in a test set of 121 PTCs. RESULTS: The expression of vimentin was increased in
      PTCs with LNM, but the one for HSP60, SOD2 and PEBP1 was increased in samples
      without LNM. HSP60 protein was up-regulated in PTCs without LNM (84.2% vs. 36.8%.
      p=0.003) and in PTCs without LNM harboring the mutation (58% vs. 41.8%. p=0.003)
      in the test set as shown by immunohistochemical staining. CONCLUSION: HSP60
      protein expression may inhibit LNM in PTCs harboring the BRAF mutation and may be
      a useful prognostic marker.

PMID- 24123004
TI  - Anti-proliferative and pro-apoptotic effects from sequenced combinations of
      andrographolide and cisplatin on ovarian cancer cell lines.
AB  - Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis
      paniculata and reported to be active against several cancer cell lines. However,
      few in-depth studies have been carried out on its effects on ovarian cancer cell
      lines alone or in combination with cisplatin (Cis), which is commonly used to
      treat ovarian cancer. The aim of this study was to determine the anti
      proliferative and apoptotic effects of Andro administered alone and in
      combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using
      five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h,
      24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm)
      and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose
      activity was lower in the resistant A2780(cisR) cell line than in the parent
      A2780 cell line, Andro was found to be three times more active in the A2780(cisR)
      cell line as compared to that in A2780 cell line. Synergism was observed when Cis
      and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage
      of apoptotic cell death was found to be greater for the 0/4 h combination of
      Andro and Cis as compared to those values from single-drug treatments. The
      results may be clinically significant if confirmed in vivo.

PMID- 24123005
TI  - Enhancing the activity of cannabidiol and other cannabinoids in vitro through
      modifications to drug combinations and treatment schedules.
AB  - Cannabinoids are the bioactive components of the Cannabis plant that display a
      diverse range of therapeutic qualities. We explored the activity of six
      cannabinoids, used both alone and in combination in leukaemic cells. Cannabinoids
      were cytostatic and caused a simultaneous arrest at all phases of the cell cycle.
      Re-culturing pre-treated cells in drug-free medium resulted in dramatic
      reductions in cell viability. Furthermore, combining cannabinoids was not
      antagonistic. We suggest that the activities of some cannabinoids are influenced
      by treatment schedules; therefore, it is important to carefully select the most
      appropriate strategy in order to maximise their efficacy. 

PMID- 24123006
TI  - Circumvention of inherent or acquired cytotoxic drug resistance in vitro using
      combinations of modulating agents.
AB  - BACKGROUND/AIM: Modulating agents are used to circumvent drug resistance in the
      clinical setting. However achievable serum concentrations are often lower than
      those which are optimal in vitro. Combination of modulating agents with non
      overlapping toxicities may overcome this obstacle. We have investigated
      combinations of three modulating agents (quinine, verapamil, and cinnarizine) to
      circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin,
      vincristine and paclitaxel. MATERIALS AND METHODS: Dose-response curves to
      cytotoxic drugs in the presence/absence of modulating agents were determined
      using colony formation and cell proliferation assays. Doxorubicin accumulation
      into cell monolayers was measured by fluorescence spectrophotometry. RESULTS:
      Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for
      certain combinations of modulating agents compared to individual effects. The
      most effective combination was quinine-plus-verapamil with the cytotoxic drug
      doxorubicin. This increase in sensitivity was associated with increased
      doxorubicin accumulation. Such enhanced activity was, however, not observed for
      all combinations of modulating agents or for all studied cytotoxic drugs.
      CONCLUSION: The findings of the present study suggest certain combinations of
      modulating agents to have a clinical role in circumventing drug resistance.
      Particular combinations of modulating agents must be carefully chosen to suit
      particular cytotoxic drug treatments.

PMID- 24123007
TI  - Cytotoxicity of dihydroartemisinin toward Molt-4 cells attenuated by N-tert-butyl
      alpha-phenylnitrone and deferoxamine.
AB  - Derivatives of artemisinin, a compound extracted from the wormwood Artemisia
      annua L, have potent anticancer properties. The anticancer mechanisms of
      artemisinin derivatives have not been fully-elucidated. We hypothesize that the
      cytotoxicity of these compounds is due to the free radicals formed by interaction
      of their endoperoxide moiety with intracellular iron in cancer cells. The effects
      of N-tert-butyl-alpha-phenylnitrone (PBN), a spin-trap free radical scavenger,
      and deferoxamine (DX), an iron chelating agent, on the in vitro cytotoxicity of
      dihyroartemisinin (DHA) toward Molt-4 human T-lymphoblastoid leukemia cells were
      investigated in the present study. Dihydroartemisinin effectively killed Molt-4
      cells in vitro. Its cytotoxicity was significantly attenuated by PBN and DX.
      Based on the data of our present and previous studies, we conclude that one
      anticancer mechanism of dihydroartemisinin is the formation of toxic-free
      radicals via an iron-mediated process. 

PMID- 24123008
TI  - Conjugated linoleate reduces prostate cancer viability whereas the effects of
      oleate and stearate are cell line-dependent.
AB  - BACKGROUND: In this study, responses to fatty acid treatments in commonly used
      prostate cancer cell culture models and variability of gene expression between
      them were determined. MATERIALS AND METHODS: PC3, DU145, LNCaP, VCaP and PNT2
      cells were treated with 100 MUM of either oleate, stearate or conjugated
      linoleate. Cell proliferation and viability were assessed using trypan blue and 3
      (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay
      respectively. Gene expression was measured using real-time polymerase chain
      reaction (PCR). RESULTS: Conjugated linoleic acid reduced cell proliferation and
      viability in all prostate cancer cell lines, whilst the effects of oleic and
      stearic acid on proliferation were found to be cell line-dependent. A reduction
      in gene expression of fatty acid desaturases was observed in prostate cancer cell
      lines compared to normal prostate cells. CONCLUSION: Differential responses of
      the cell lines investigated here to fatty acid treatment suggest that multiple
      prostate cancer cell line models should be used when designing experiments aimed
      at examining lipid metabolism in prostate cancer.

PMID- 24123009
TI  - Effects of SRC and STAT3 upon gap junctional, intercellular communication in lung
      cancer lines.
AB  - BACKGROUND: We have previously demonstrated a positive correlation between SRC
      and its effector signal transducer and activator of transcription-3 (STAT3), and
      a reverse relation between SRC and gap junctional communication (GJIC) in seven
      non-small cell lung cancer (NSCLC) lines. Since a number of oncogenes besides SRC
      can affect GJIC, here we examined the actual contribution of the SRC/STAT3 axis
      to GJIC suppression. MATERIALS AND METHODS: SRC and STAT3 activity levels were
      examined in SK-LuCi-6, LC-T, QU-DB, SW-1573, BH-E, Calu-6, FR-E, SK-MES, H1299,
      BEN, WT-E, A549 and SHP-77 cells by western blott analysis, probing with
      antibodies specific for SRC-ptyr418 or STAT3-ptyr705. GJIC was examined by in
      situ electroporation. RESULTS: Confluence of all cultured NSCLC cells tested
      induces a dramatic increase in STAT3 activity, which is independent of SRC
      action. In addition, the LC-T line had high STAT3-705, despite the fact that SRC
      418 expression was low, indicating that other, SRC-independent factors must be
      responsible for STAT3 activation and GJIC suppression in these cells; however, BH
      E and SHP-77 cells with low GJIC, both SRC-418 and STAT3-705 expression were low,
      indicating that GJIC suppression can be independent of the SRC/STAT3 axis
      altogether. Our results also show that STAT3 inhibition does not restore GJIC in
      any of the examined lines, while in the non-transformed rat F111 fibroblast line
      which has extensive GJIC, STAT3 inhibition actually eliminated junctional
      permeability. CONCLUSION: Our results indicate a further level of complexity in
      the relationship between SRC, STAT3 and GJIC in NSCLC than what has been
      previously demonstrated. In addition, STAT3 is actually required for, rather than
      suppressing GJIC.

PMID- 24123010
TI  - Citric acid induces cell-cycle arrest and apoptosis of human immortalized
      keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling
      pathways.
AB  - Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and
      skincare products. However, there is concern regarding its safety for the skin.
      In this study, we investigated the cytotoxic effects of citric acid on the human
      keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5
      12.5 mM for different time periods. Cell-cycle arrest and apoptosis were
      investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining,
      flow cytometry, western blot and confocal microscopy. Citric acid not only
      inhibited proliferation of HaCaT cells in a dose-dependent manner, but also
      induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S
      phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein
      (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra
      large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced
      apoptosis via caspase-dependent and caspase-independent pathways. Citric acid
      also activated death receptors and increased the levels of caspase-8, activated
      BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor
      (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis
      through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The
      study results suggest that citric acid is cytotoxic to HaCaT cells via induction
      of apoptosis and cell-cycle arrest in vitro. 

PMID- 24123011
TI  - Adipose-derived stem cells induced EMT-like changes in H358 lung cancer cells.
AB  - Despite the potential utility of adipose-derived mesenchymal stem cells (ADSCs)
      in regenerative medicine, not much is known about their interaction with residual
      cancer cells. Here, we studied the direct co-culture effects of ADSCs on H358
      lung cancer cells. The paracrine effects of ADSCs were compared to those of the
      cancer-associated fibroblasts. Extracellular matrix and conditioned media were
      used to determine the underlying molecules. Time-lapse photography, fluorescence
      activated cell sorting (FACS), scratch assays, immunocytochemistry, and reverse
      transcription polymerase chain reaction were used to analyze the effects. ADSCs
      differentiated into myofibroblasts expressing alphaSMA, and H358 cells strongly
      attached to them. EMT-like changes were observed in H358 cells which were
      inhibited by gamma-secretase inhibitor, a-NOTCH inhibitor. Surprisingly, both
      mesenchymal and epithelial genes were expressed, and the effects were readily
      reversed when cells were sorted by FACS. These data suggest that ADSCs may
      differentiate into tumor stroma that plays supportive roles during cancer
      progression.

PMID- 24123012
TI  - Nox4-derived ROS signaling contributes to TGF-beta-induced epithelial-mesenchymal
      transition in pancreatic cancer cells.
AB  - Transforming growth factor (TGF)-beta induces epithelial-mesenchymal transition
      (EMT) in pancreatic adenocarcinoma. In this study, we investigated how NADPH
      oxidase (Nox) 4-generated reactive oxygen species (ROS) regulate TGF-beta-induced
      EMT in pancreatic cancer cells. MATERIALS AND METHODS: Pancreatic cancer cells
      were transfected with Nox4 siRNAs or PTP1B mutants and subjected to TGF-beta
      induced EMT assay. Expression of Nox4, TGF-beta, and N-cadherin was
      immunohistochemically-examined with patient tumor samples. RESULTS: Treatment of
      pancreatic cancer cells with TGF-beta induced Nox4 expression, indicating that
      Nox4 represents a major source for ROS production. The Nox4 inhibitor diphenylene
      iodonium and Nox4 siRNAs blocked TGF-beta-induced EMT phenotype including
      morphological changes, augmented migration, and altered expression of E-cadherin
      and Snail. Furthermore, PTP1B as a redox-sensor for Nox4-derived ROS participated
      in TGF-beta-promoted EMT. Nox4, TGF-beta, and N-cadherin were up-regulated in
      tumors from pancreatic cancer patients. CONCLUSIONS: These findings suggest that
      Nox4-derived ROS, at least in part, transmit TGF-beta-triggered EMT signals
      through PTP1B in pancreatic cancer.

PMID- 24123013
TI  - In vitro induction of apoptosis and necrosis by new derivatives of daunorubicin.
AB  - BACKGROUND/AIM: The comparative effects of daunorubicin, and its new formamidine
      derivatives containing either a morpholine moiety (DAUFmor) or a
      hexamethyleneimine moiety (DAUFhex) in the amidine group, on induction of
      programmed cell death were determined. MATERIALS AND METHODS: The experiments
      were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute
      myeloblastic leukemia ML-1 cells. The research was conducted using the flow
      cytometry annexin V-fluorescein (FITC)/propidium iodide (PI) method and
      tetramethylrhodamine ethyl ester (TMRE) assay. RESULTS: The various patterns of
      temporary changes of early apoptotic cells, late apoptotic and necrotic cells,
      and in the frequency of the acute leukemia cells with high values of
      mitochondrial membrane potential (MMP) were found. Phosphatidylserine
      externalization, plasma membrane disruption, and changes in MMP occurring in the
      leukemia cells were dependent on the agent tested, its concentration, the time
      intervals after daunorubicin, DAUFmor, and DAUFhex application, and on the
      leukemia cell line used. CONCLUSION: The structural modifications of daunorubicin
      producing two new analogs, DAUFmor and DAUFhex, induced the different responses
      of MOLT-4 and ML-1 cells to triggering of programmed death.

PMID- 24123014
TI  - AG11, a novel dichloroflavanone derivative with anti-mitotic activity towards
      human bladder cancer cells.
AB  - BACKGROUND: New chemotherapy drugs should be investigated to improve survival of
      patients with advanced bladder cancer. Here, we report the synthesis and
      evaluation of AG11, a new flavanone derivative obtained through cyclization of
      its chalcone precursor CB11. MATERIALS AND METHODS: The effect of AG11 on cell
      viability was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium
      bromide assay and apoptotic cell death was analyzed by flow cytometry. Finally,
      the effect of AG11 on tubulin polymerization in vitro and microtubule
      distribution across the cells was investigated. RESULTS: AG11 was found to have
      an IC50 (half-maximal inhibitory concentration) of 4.6 MUM and its inhibitory
      effect on RT4 cells proliferation is associated with a cell-cycle arrest in G2+M
      phases followed by apoptosis after a 48 h treatment. AG11 prevented
      polymerization of purified tubulin in a concentration-dependent manner in vitro
      and disrupted mitotic spindle formation in cells. CONCLUSION: AG11 appears to be
      an attractive scaffold for further development of a structurally simpler new anti
      microtubule agents.

PMID- 24123015
TI  - Repression of cell proliferation and androgen receptor activity in prostate
      cancer cells by 2'-hydroxyflavanone.
AB  - BACKGROUND: Prevention of the development of castration-resistant from hormone
      naive prostate cancer is an important issue in maintaining the quality of life of
      the patients. We explored the effect of 2'-hydroxyflavanone on proliferation and
      androgen responsiveness using prostate cancer cell lines. MATERIALS AND METHODS:
      To investigate the effect of 2'-hydroxyflavanone on proliferation, prostate
      cancer cells were treated with 2'-hydroxyflavanone. Androgen-responsiveness in
      LNCaP cells was confirmed by luciferase assay after transfection of luciferase
      reporter driven by prostate specific antigen promoter. To detect androgen
      receptor (AR) expression, reverse transcriptase polymerase chain reaction and
      western blot analysis were conducted. RESULTS: 2'-Hydroxyflavanone inhibited the
      proliferation of PC-3 and DU145 cells by induction of apoptosis. 2'
      Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by
      androgens and attenuated androgen-responsiveness through down-regulation of AR
      protein. CONCLUSION: 2'-Hydroxyflavanone not only inhibited proliferation of
      prostate cancer cells, but also repressed androgen-responsiveness, suggesting
      that it might be a useful agent in preventing recurrence of prostate cancer.

PMID- 24123016
TI  - Activity of LaSOM 65, a monastrol-derived compound, against glioblastoma
      multiforme cell lines.
AB  - BACKGROUND/AIM: Despite recent progress in glioblastoma treatment, prognosis is
      still poor. Monastrol is a kinesin spindle protein (KSP) inhibitor and anticancer
      effects for this molecule have been reported. Here we describe the effect of
      LaSOM 65, a monastrol derivated compound, against glioma cell lines. MATERIALS
      AND METHODS: Cell counting, viability assay, lactate dehydrogenase (LDH)
      activity, cell-cycle analysis, immunofluorescence and organotypic hippocampal
      slice cultures were performed. RESULTS: LaSOM 65 reduced cell number and cell
      viability of gliomas cells, but did not cause arrest in the cell cycle at the
      G2/M phase. Measurement of LDH activity showed that LaSOM 65 induces necrosis
      after 48 h of treatment. CONCLUSION: LaSOM 65 appears to a be promising new
      molecule to treat glioblastoma since it promotes a decrease of cell growth and
      cell viability of glioma cells in vitro and does not induces the neurotoxic
      characteristics of the anti-mitotic drugs currently used.

PMID- 24123017
TI  - Low production of reactive oxygen species and high DNA repair: mechanism of
      radioresistance of prostate cancer stem cells.
AB  - BACKGROUND: Cancer stem cells (CSCs) are resistant to radiotherapy and are
      responsible for tumor recurrence of various malignant tumors, including prostate
      cancer. MATERIALS AND METHODS: In order to define the radioresistance mechanism
      of prostate CSCs, their proliferative activity, cell cycle distribution,
      expression of CD133 stem cell marker, reactive oxygen species (ROS) production,
      and DNA repair efficiency were examined using prostatospheres and adherent LNCaP
      cells as a model of prostate CSC and bulk model of differentiated cells,
      respectively. RESULTS: Compared to adherent cells, prostatospheres exhibited
      greater number of low-to-intermediate ROS-producing cells and CD133-positive
      cells. Prostatospheres showed higher expression of DNA repair proteins after
      ionizing radiation (IR). CONCLUSION: Low vulnerability to ROS-induced cellular
      damage and the efficient repair of IR-induced DNA injury may explain the
      radioresistance of prostate CSCs. Therefore, increasing ROS-induced cytotoxicity
      and inhibition of DNA repair in prostate CSCs may help achieve complete
      eradication of prostate CSCs by radiotherapy.

PMID- 24123018
TI  - Phase I trial of carboplatin and etoposide in combination with panobinostat in
      patients with lung cancer.
AB  - A phase I trial consisting of panobinostat (a HDAC inhibitor), carboplatin and
      etoposide was conducted in patients with lung cancer. PATIENTS AND METHODS:
      Patients received carboplatin AUC5 on day 1 and etoposide 100 mg/m(2) on days 1,
      2 and 3, every 21 days. Concurrent oral panobinostat was given 3 times weekly on
      a 2-weeks-on and 1-week-off schedule during the 4-6 cycles of chemotherapy and
      then continued as maintenance therapy. RESULTS: Six evaluable patients were
      treated at the first dose level of panobinostat (10 mg). Dose-limiting toxicity
      occurred in two patients (33%) during the first cycle. One patient developed
      grade 4 thrombocytopenia and another grade 4 febrile neutropenia. Therefore, the
      study was suspended based on the pre-specified study design. No recommended phase
      II starting dose was established. CONCLUSION: The addition of panobinostat to
      carboplatin and etoposide was not tolerable at the lowest dose level tested in
      this trial. Further research and development into this combination is not
      recommended.

PMID- 24123019
TI  - Comprehensive head and neck radiotherapy dose-volume constraints do not apply to
      smaller volumes.
AB  - AIM: To investigate the impact of definitive radiation therapy (RT) in the
      management of early glottic cancer on clinical RT-induced dysphagia (RID) and
      carotid vasculopathy (RICV). PATIENTS AND METHODS: This is a single-institution
      retrospective study. From January 1997 to 2010, 253 patients, with early glottic
      cancer, underwent RT with (60)Co or LINAC-6 MV photons. RT fields with wedge pair
      and daily 5-mm bolus were applied in all patients treated with 6-MV photons to
      avoid under-dose of the anterior laryngeal structures. The whole larynx (LX),
      pharyngeal constrictors (PCs), and carotid arteries (CA) were contoured and dose
      volume histograms (DVHs) were generated to assess the delivered dose. The median
      age of patients was 65 years (range; 28-93), Caucasians were 80%, males were 87%,
      and 23% had T2 lesions. RESULTS: After a median follow-up of seven years (range;
      1.5-12), the median dose and fraction size delivered to the LX were 63 and 2.25
      Gy, respectively. The mean doses to the LX, PC, and CA were 57 Gy delivered to 34
      cm(3), 54 Gy to 15 cm(3), and 60 Gy to 4 cm(3), respectively. The LX, PC and CA
      V60 and V65 were (77 and 71), (70 and 52) and (84 and 51), respectively. Patients
      with acute dysphagia grades 1, 2, and 3 or more were 81, 19%, and zero,
      respectively; none had clinically RID or RICV. CONCLUSION: Small-volume RT up to
      67.5 Gy at 2.25 Gy per fraction, is not a predictor of RID or RICV. Separate
      delineation of the aforementioned critical structures, as well as others, may
      better identify dose tolerances to maintain function and further prioritize the
      importance of structures in RID and RICV.

PMID- 24123020
TI  - Early-stage central lung cancer and volumetric modulated arc therapy: a
      dosimetric case study with literature review.
AB  - BACKGROUND/AIM: In the present article we review on the use of Volumetric
      Modulated Arc Therapy (VMAT) for a small lung nodule that was centrally located
      in close proximity to the mediastinal structures. CASE REPORT: An inoperable
      patient with central, clinical stage IA adenocarcinoma of the right lung was
      treated with external-beam radiation therapy of 52.5 Gy in 15 factions. A single
      360 degrees  coplanar arc VMAT plan (360-VMAT) was used for treatment and
      compared to step-and-shoot Intensity Modulation Radiotherapy (IMRT) and a single
      180 degrees  ipsilateral partial arc VMAT plan (180-VMAT). RESULTS: Planning
      Target Volume (PTV) coverage was not different, and 360-VMAT had the highest dose
      homogeneity. Both 360-VMAT and 180-VMAT reduced esophageal dose compared to IMRT.
      While IMRT had the lowest lung dose, all 3 plans achieved acceptable sparing of
      the lung. 180-VMAT had the highest dose conformity. Both 360-VMAT and 180-VMAT
      improved esophageal sparing compared to IMRT. CONCLUSION: Use of VMAT in early
      stage, centrally located NSCLC is a promising treatment approach and merits
      additional investigation.

PMID- 24123021
TI  - Retrospective analysis of the efficacy of two cycles of M-VAC neoadjuvant
      chemotherapy followed by radical cystectomy for muscle-invasive bladder cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy before radical cystectomy for muscle
      invasive bladder cancer is a commonly used treatment modality. However, in terms
      of chemotherapeutic regimens and the number of cycles of neoadjuvant
      chemotherapy, there is yet no international consensus, as various studies
      indicate the efficacy of several platinum-based combination chemotherapeutic
      regimens. We determined the efficacy of two cycles of neoadjuvant chemotherapy
      with methotrexate, vinblastine, adriamycin, and cisplatin followed by radical
      cystectomy. PATIENTS AND METHODS: The study population included patients with
      clinical stage T2 - T4a, N0, M0 bladder cancer who underwent radical cystectomy.
      Clinical courses were compared between 27 patients treated with two cycles of M
      VAC neoadjuvant chemotherapy and 25 treated with cystectomy alone. RESULTS: The
      incidence of pT0 was 25.9% in the group treated with neoadjuvant chemotherapy.
      The probabilities of disease-free and cause-specific survival were significantly
      higher in patients treated with, than without neoadjuvant chemotherapy. On
      univariate Cox proportional hazards regression analysis for the patients treated
      with neoadjuvant chemotherapy, pathological stage and the pathological findings
      of venous involvement were significant prognostic factors. CONCLUSION: The
      results of this retrospective study demonstrated the clinical effectiveness of
      two cycles of neoadjuvant M-VAC chemotherapy for muscle-invasive bladder cancer.

PMID- 24123022
TI  - Survival in patients with metastatic spinal cord compression from prostate cancer
      is associated with the number of extra-spinal organs involved.
AB  - BACKGROUND/AIM: To investigate the predictive value of the number of extra-spinal
      organs involved by metastases for survival in metastatic spinal cord compression
      (MSCC) from prostate cancer. PATIENTS AND METHODS: In 95 patients irradiated with
      10 * 3 Gy for MSCC from prostate cancer, seven factors were investigated: Age,
      performance score, number of involved vertebrae, interval from prostate cancer
      diagnosis to MSCC, pre-radiotherapy ambulatory status, time to motor deficits
      development, number of involved extra-spinal organs. RESULTS: Six-month survival
      rates for 0, 1 and >= 2 involved extra-spinal organs, were 81, 53 and 33%,
      respectively (p<0.001). On multivariate analysis, the number of involved extra
      spinal organs maintained significance (risk ratio 1.88, p=0.023). Better
      performance score (p<0.001), longer interval from prostate cancer diagnosis to
      radiotherapy of MSCC (p<0.001), and being ambulatory prior to radiotherapy
      (p=0.001) were also positively associated with survival. CONCLUSION: The number
      of extra-spinal organs involved by metastases predicts survival in patients with
      MSCC from prostate cancer.

PMID- 24123023
TI  - Predictive factors of non-sentinel lymph node involvement in patients with
      invasive breast cancer and sentinel node micrometastases.
AB  - Patient-related, tumor-related, and sentinel node (SN)-related factors have been
      identified with the aim of predicting non-SN status in patients with SN
      micrometastases. According to our previous experience, primary tumor size
      (p=0.005) and the presence of lymphovascular invasion (LVI) (p=0.000)
      significantly predicted non-SN status in patients with SN micrometastasis;
      moreover, non-SN metastases were never detected in patients with pT1a-1b, G1, and
      no LVI. A prospective assessment was undertaken in a validation set of 126
      patients to confirm these findings. Univariate analysis indicated that primary
      tumor size (p=0.05), Scarff-Bloom-Richardson (SBR) grade (p=0.008), LVI
      (p=0.001), and the number of mitoses/mm(2) (p=0.01) were significant predictors
      of non-SN status. By logistic regression analysis, tumor size (p=0.03), LVI
      (p=0.001), grade (p=0.003) and the number of mitoses/mm(2) (p=0.01) were the only
      variables remaining in the model. Three subsets of patients were identified: i)
      18.3% of patients (pT1, G1, and no LVI) had tumor-negative non-SN (no risk
      group); ii) 37.3% of patients (number of mitoses/mm(2) <10, SBR grade II-III) had
      a rate of tumor-positive non-SN <15% (intermediate risk); iii) 44.4% of patients
      had a mean rate of non-SN involvement of 46% (high risk). By these parameters,
      more than 50% of patients could be selectively spared unnecessary axillary lymph
      node dissection without staging or therapeutic benefit, especially in patients
      with well-differentiated pT1 tumors without LVI.

PMID- 24123024
TI  - Thoracoscopic esophagectomy in the prone position for esophageal cancer with
      right aortic arch: case report.
AB  - A congenital anomaly of the right aortic arch (RAA) is rare, and esophageal
      cancer associated with the vascular ring is even more rare. In such cases, it is
      very important to understand the anatomical situation in the upper mediastinum in
      order to perform a safe and curative operation. A 52-year-old man who presented
      with odynophagia was admitted to our department after a diagnosis of advanced
      esophageal cancer. Chest computed tomography revealed an RAA with an aberrant
      subclavian artery and showed that the esophagus was completely encircled by the
      RAA, aortic diverticulum, and pulmonary artery. By the thoracoscopic view with
      the patient in the prone position, we were able to easily and safely identify the
      anatomical location of the upper mediastinum and successfully perform
      thoracoscopic esophagectomy. To the best of our knowledge, this is the first
      report of a patient undergoing total thoracoscopic esophagectomy in the prone
      position without thoracotomy. 

PMID- 24123025
TI  - Free circulating DNA as a biomarker of prostate cancer: comparison of
      quantitation methods.
AB  - AIM: To identify a simpler method of free circulating DNA (fcDNA) quantitation
      that may improve the specificity of the prostate cancer prostate-specific antigen
      (PSA) screening test. MATERIALS AND METHODS: The patient group consisted of 241
      men with elevated PSA/abnormal digital rectal exam (DRE), undergoing prostate
      biopsy. Serum fcDNA levels were measured by UV absorbance and PicoGreen. Results
      were compared to previously published quantitative polymerase chain reaction
      (qPCR) data. RESULTS: We found that levels of fcDNA measured by PicoGreen
      correlated well with those measured by qPCR (r=0.8552). In the patient group with
      PSA >4 to 10 ng/ml, those with fcDNA (PicoGreen) >53.1 ng/ml were at increased
      risk for prostate cancer compared to those with fcDNA <= 53.1 ng/ml. Moreover, we
      found that measuring fcDNA levels by PicoGreen does not compromise the negative
      predictive value, accuracy or specificity of the qPCR fcDNA test. CONCLUSION: If
      validated in larger studies, PicoGreen quantitation of fcDNA could serve as a
      simple method to aid in prostate cancer diagnosis.

PMID- 24123026
TI  - Therapeutic response of untreatable hepatocellular carcinoma after application of
      the immune modulators IL-2, BCG and melatonin.
AB  - AIM: Application of immunotherapy to a patient with untreatable hepatocellular
      carcinoma. CASE REPORT: The patient had a tumor of 60 mm in the liver. The
      pathological anatomic diagnosis was adenoma. However, after surgery of the tumor
      seven new lesions arose, showing that the original tumor had been a
      hepatocellular carcinoma. In addition, when hepatocellular adenomas grow to a
      size of more than 6-8 cm, they are considered cancerous and thus become a risk
      for hepatocellular carcinoma. The patient was treated with interleukin-2,
      Bacillus Calmette Guerin, and melatonin. RESULTS: During treatment, the alpha
      fetoprotein levels in blood fell from 5,000 IU/ml to zero, at which level it
      remained during the follow-up period of two years. No tumor was detectable on MRI
      and CT. Six years after the diagnosis of untreatable hepatocellular carcinoma,
      the patient remains in a good condition. CONCLUSION: In this case, combined
      immunomodulating therapy was effective. For patients with metastasized tumors of
      the liver who are not suitable for conventional therapy, immunomodulation may
      delay tumor progression, induce tumor regression, or even be curative in some
      patients. Immunotherapeutic approaches combined with conventional methods for
      hepatocellular carcinoma treatment may be able to improve therapeutic efficacy.

PMID- 24123027
TI  - Hypofractionation with VMAT versus 3DCRT in post-operative patients with prostate
      cancer.
AB  - AIMS: To retrospectively evaluate and compare the incidence of acute
      genitourinary (aGU), upper gastrointestinal (uGI) and rectal (lGI) injuries after
      radiotherapy with hypo-fractionation by volumetric modulation arc therapy (VMAT,
      the Hypo-RapidArc group) and conventional fractionation by three-dimensional
      conformal radiotherapy (3DCRT) in patients with localized prostate cancer
      treated, after radical prostatectomy, with prostatic bed irradiation. PATIENTS
      AND METHODS: Between 2007 and 2012, 84 consecutive patients with clinically
      localized prostate cancer submitted to radical prostatectomy were also treated
      with irradiation to the prostate bed. Forty-five received 3DCRT and 39 Hypo
      RapidArc. The median age was 67 and 69 years for 3DCRT and Hypo-RapidArc groups
      respectively. The median dose to the prostatic bed was 70 Gy in both groups: 2
      Gy/fraction in the 3DCRT group and 2.5 Gy/fraction in the Hypo-RapidArc group.
      After radical prostatectomy, the median time-to-RT was 15 and 16 months
      respectively. Acute and late toxicities were scored according to the Radiation
      Therapy and Oncology Group/European Organization for Research and Treatment of
      Cancer system. RESULTS: Grade 2aGU was recorded in 16% of cases in the 3DRCT
      group and in 10% in the Hypo-RapidArc group. No acute grade 2 upper
      gastrointestinal (uGI) toxicities were found in the 3DCRT versus 5% in the Hypo
      RapidArc group. The incidence of grade 2 lower gastrointestinal (lGI) toxicities
      was 22% in the 3DCRT group versus 15% in the Hypo-RapidArc group. No grade 3 or
      greater toxicities were found in either group. In both groups, good planning
      target volume coverage was achieved: V95% was recorded as 96.3 +/- 3.6% (mean +/-
      standard deviation) and 95.7 +/- 8.9 for the 3DRCT and the Hypo-RapidArc groups,
      respectively. The mean rectal volume dose receiving at least 70 Gy was 9.1 +/-
      10.8% and 0.1 +/- 0.6% respectively. The mean dose to the bladder was 49.5 +/-
      12.3 Gy and 37.2 +/- 5.2 Gy respectively. Significant correlation between late
      rectal toxicity and the maximum dose to the rectum, V70Gy, was found in the 3DCRT
      group, while no significant correlations were found for acute toxicity.
      CONCLUSION: The results presented in this study demonstrate the feasibility of a
      moderate hypo-fractionation regimen with RapidArc in the postoperative setting.
      Longer-term data are needed to confirm late toxicity profiles.

PMID- 24123028
TI  - Paraneoplastic thrombocytosis in breast cancer.
AB  - BACKGROUND: Elevated platelet count at the time of diagnosis has been suggested
      to identify a subset of patients with cancer (e.g. ovarian and lung
      adenocarcinoma) and poor prognosis. The evidence on the incidence and prognostic
      significance of thrombocytosis in breast cancer is, however, incomplete. PATIENTS
      AND METHODS: We performed a retrospective analysis of 127 consecutive patients
      with breast cancer at our Institution. RESULTS: None of the 81 newly- diagnosed
      patients had an elevated platelet count (mean=252 * 10(6)/l). Out of the 31
      patients with metastatic disease, one exhibited mild thrombocytosis (445 *
      10(6)/l) but the mean value (239 * 10(6)/l) was similar to that seen in patients
      with localized disease. CONCLUSION: We conclude that thrombocytosis in breast
      cancer is rare and thus, unlike in other types of cancer, and has limited (if
      any) value in clinical decision making.

PMID- 24123029
TI  - Weekly paclitaxel as second-line chemotherapy in Japanese patients with advanced
      gastric cancer.
AB  - AIM: The use of weekly paclitaxel (wPTX) has become a common practice as second
      line chemotherapy in Japanese patients with advanced gastric cancer. The aim of
      the present study was to assess the efficacy of wPTX. PATIENTS AND METHODS: We
      retrospectively analyzed data from 229 patients with advanced gastric cancer who
      received wPTX as second-line chemotherapy between March 2001 and January 2011 at
      our hospital. Patients received PTX at a dose of 80 mg/m(2) on days 1, 8, 15 of a
      28-day cycle. Response and survival were evaluated. RESULTS: The overall response
      rate was 12.5% in 96 patients who had measurable lesions that were assessable for
      response. In 107 patients who had malignant ascites, the response rate for
      therapy of ascites was 38.3%. The median progression-free survival was 3.6
      months, and the median overall survival was 6.3 months. Multivariate analysis
      revealed that the number of metastatic sites [hazard ratio (HR)=1.56, p=0.009],
      bone metastasis (HR=2.11, p=0.006), ascites (HR 1.75, p<0.001), and the presence
      of the primary lesion (HR=1.77, p<0.001) were independent prognostic factors of
      poor survival. CONCLUSION: wPTX is an effective regimen for advanced gastric
      cancer refractory to first-line chemotherapy.

PMID- 24123030
TI  - Whole-body bioelectrical impedance analysis in assessing upper-limb lymphedema
      after breast cancer therapy.
AB  - AIM: The purpose of this prospective study was to evaluate single-frequency whole
      body bioelectrical impedance analysis (BIA) as a predictor for the onset of edema
      of the upper limb in patients undergoing treatment for breast cancer. MATERIALS
      AND METHODS: Whole-body BIA was performed before surgery, as well as at two days,
      and one, three, six and twelve months after surgery. RESULTS: Sixty women
      undergoing breast cancer surgery were examined, with loss of follow-up of 18
      patients. Seven patients (14.3%) developed an edema of the upper limb within the
      first 12 months after surgery. Resistance (R) using whole-body BIA showed a
      fairly good performance in terms of sensitivity (85.71%) and specificity (97.4%)
      at predicting edema. The positive predictive value of 54.6% was unsatisfactory,
      whereas the negative predictive value was 97.4%. CONCLUSION: Resistance in whole
      body BIA can be used to rule-out a developing edema of the upper limb.

PMID- 24123031
TI  - Postoperative 5-FU based radiochemotherapy in rectal cancer: retrospective long
      term results and prognostic factors of a pooled analysis on 1,338 patients.
AB  - AIM: To evaluate survival outcomes of patients in pStage II-III rectal cancer
      treated with adjuvant 5-fluorouracil-based radiochemotherapy and to
      retrospectively analyze the impact of prognostic variables on local control,
      metastasis-free survival and cause-specific survival. PATIENTS AND METHODS: A
      total of 1,338 patients, treated between 1985-2005 for locally advanced rectal
      cancer, who underwent surgery and postoperative 5-fluorouracil-based
      chemoradiation, were selected. RESULTS: The actuarial 5- and 10-year outcomes
      were: local control 87.0%-84.1%, disease-free survival 61.6%-52.1%, metastasis
      free survival 72.0%-67.2%, cause-specific survival 70.4%-57.5%, and overall
      survival 63.8%-53.4%. Better outcomes were observed in patients with IIA, IIIA
      stage. Multivariate analyses showed that variables significantly affecting
      metastasis-free survival were pT4 and pN2, while for cancer-specific survival
      those variables were age >65 years, pT4, pN1, pN2, distal tumors and number of
      lymph nodes removed <= 12. CONCLUSION: This study confirmed that among stage II
      III rectal cancer patients there are subgroups of patients with different
      clinical outcomes.

PMID- 24123032
TI  - First description of a hybrid tumor of the sublingual gland.
AB  - BACKGROUND: Hybrid tumours of the salivary glands are rare neoplasms. They are
      composed of at least two different tumour entities located in the same
      topographic area and account for only 0.1% of all salivary gland tumours. The
      most common component is an adenoid cystic carcinoma. There are several possible
      forms of hybrid tumours, which are most commonly located in the parotid gland.
      CASE REPORT: We report on a 59-year-old female, who presented with a lesion of
      the caruncula of the left sublingual gland. The biopsy showed an adenoid cystic
      carcinoma in combination with a salivary duct carcinoma. Treatment consisted of
      tumour resection, bilateral selective neck dissection and adjuvant radiotherapy.
      Histopathologically, at least 30% of the tumour mass was composed of a salivary
      duct carcinoma and 70% of an adenoid cystic carcinoma. At 58 months after
      treatment, the patient is alive without evidence of recurrent disease.
      CONCLUSION: To our knowledge, the presented case is the first description of a
      hybrid tumour of the sublingual gland. Furthermore, the post-therapeutic course
      is encouraging, as hybrid tumours of the salivary glands usually have a poor
      prognosis.

PMID- 24123033
TI  - The prognostic significance of WNT pathway in surgically-treated colorectal
      cancer: beta-catenin expression predicts for disease-free survival.
AB  - BACKGROUND: The wingless-type MMTV integration site family of proteins (WNT)
      pathway is highly involved in colorectal cancer development. The aim of this
      study was to explore the prognostic significance and clinicopatological
      correlations of this pathway in a cohort of surgically-treated patients with non
      metastatic colorectal cancer in relation to the site of expression of pathway
      proteins. MATERIALS AND METHODS: Immunohistochemical expression of nuclear cyclin
      D1, membranous E-cadherin and P-cadherin, membranous and nuclear beta-catenin in
      the invasive front (IF), the tumor center (TC), as well as their mean, were
      assessed in 106 paraffin-embedded tissue samples. Adenomatous Polyposis Coli
      (APC), Axin-2 (AXIN2), cyclin-D1 (CCND1), Matrix Metalloproteinase-7 (MMP7),
      Secreted Frizzled Related Protein (SFRP) 1, 2 and 4 and WNT5A were evaluated by
      RT PCR. RESULTS: Membranous beta-catenin expression was statistically reduced in
      the IF. Cyclin-D1 was reduced in tumors arising closer to the rectum. Reduced
      nuclear expression of cyclin-D1 in the IF was associated with lymphatic, venous
      and perineural invasion. Loss of membranous beta-catenin in the TC was more
      common among N2 tumors. Higher SFRP4 mRNA was associated with advanced T stage.
      In univariate analysis, membranous expression of beta-catenin in TC and IF, and
      their mean, was associated with longer disease-free survival (DFS). In
      multivariate analysis, tumor stage and mean beta-catenin expression were
      prognostic for longer DFS (hazard ratio=0.33; p=0.01). beta-Catenin expression in
      the IF remained significant when the mean expression was not included in the
      multivariate analysis (hazard ratio=0.41; p=0.028). CONCLUSION: Mean membranous
      expression of beta-catenin, as well as that in the IF, is prognostic for longer
      DFS in patients with non metastatic colorectal cancer.

PMID- 24123034
TI  - Radiotherapy and concurrent metronomic chemotherapy in hormone-refractory
      prostate carcinoma: a Phase I study.
AB  - AIM: To determine the maximum tolerated dose of hypofractionated radiotherapy
      (HFRT) plus concurrent metronomic chemotherapy in patients with hormone
      refractory prostate cancer (HRPC). PATIENTS AND METHODS: A Phase I clinical trial
      was performed with cohorts of three to six patients per group. Eligible patients
      had HRPC without distant metastases. The radiotherapy dose was escalated in a
      stepwise fashion as follows: 60, 65, and 70 Gy at levels 1, 2, and 3,
      respectively (25 fractions: levels 1-2, and 26 fractions: level 3). RESULTS: Nine
      patients were enrolled. The radiotherapy dose was escalated from 60 to 70 Gy
      without any dose-limiting toxicity. The most common grade 1/2 toxicities were
      hematuria, dysuria, diarrhea and rectal-perirectal pain. The overall objective
      response rate was 9/9 (100%) (95% CI=66.4%-100%). The median time-to-progression
      was 19 months. CONCLUSION: In the challenging setting of HRPC, HFRT up to 70 Gy
      with concurrent metronomic chemotherapy was well-tolerated and yielded
      encouraging disease control.

PMID- 24123035
TI  - Preoperative neutrophil-to-lymphocyte ratio predicts clinical outcome in patients
      with stage II and III colon cancer.
AB  - AIM/ BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a combined indicator
      of inflammation and immunology, is as yet unidentified regarding the clinical
      outcome of stage II and III colon cancer patients. We evaluated the effect of NLR
      on time-to-recurrence (TTR) and overall survival (OS) in selected patients.
      PATIENTS AND METHODS: A total of 504 patients with stage II and III colon cancer
      were included in this retrospective study. Preoperative NLR with a cut-off level
      of 4 was associated with TTR and OS. RESULTS: In univariate analysis, elevated
      NLR was significantly associated with decreased TTR (p=0.001) and remained
      significant in multivariate analysis (p=0.006). Patients with NLR >4 showed a
      median TTR of 62.2 months. In contrast, patients with NLR <= 4 had a median TTR
      of 92.6 months. CONCLUSION: This study suggests that preoperative NLR may be an
      independent prognostic marker for TTR in stage II and III colon cancer patients.

PMID- 24123036
TI  - Prevalence of H. pylori infection and atrophic gastritis among symptomatic and
      dyspeptic adults in Kazakhstan. A hospital-based screening study using a panel of
      serum biomarkers.
AB  - BACKGROUND: Health authorities of Kazakhstan are seeking for effective measures
      to interrupt the untoward trend, projected to increase the current number of
      gastric cancer (GC) cases (n=3,316) by 50% until the year 2030. OBJECTIVE: Use of
      a non-invasive blood test with four stomach-specific biomarkers [Pepsinogen-I (PG
      I) and -II (PG-II), amidated gastrin-17 (G-17), and Helicobacter pylori (HP) IgG
      antibodies], to assess for the prevalence of stomach conditions: Helicobacter
      pylori (HP) infection and atrophic gastritis (AG), both known to increase GC risk
      of in Kazakhstan. MATERIALS AND METHODS: A cohort of 835 (symptomatic and
      asymptomatic) cases (473 women and 362 men)(median age 46.8 years; range 13.6
      74.8) was examined with a panel of biomarkers. Results were assigned in five
      categories: 1) Healthy stomach, 2) HP infection, 3) atrophic gastritis (AG) of
      the antrum, 4) AG of the corpus, and 5) AG of both antrum and corpus
      (pangastritis). RESULTS: The distribution in these five categories was identical
      in both sexes (p=0.259). Healthy stomach was detected only in 196 (23.5%)
      subjects, whereas the vast majority, 62.3% (n=519) had HP infection (with no AG).
      In 118 (14.1%) subjects, results were consistent with AG; in antrum (n=72),
      corpus (n=42) or pangastritis (n=4). Prevalence of AG increased with patient's
      age in both sexes. There was no age-related pattern in biomarker levels, and only
      slight differences between the genders. CONCLUSION: While capable of detecting
      the subjects at risk for GC (HP or AG), GP seems to be a cost-effective means to
      intervene the current ominous trend in GC incidence in Kazakhstan.

PMID- 24123037
TI  - Weekly non-pegylated liposomal doxorubicin chemotherapy in heavily pre-treated
      patients with metastatic breast cancer.
AB  - BACKGROUND: Due to its low cardiac toxicity, non-pegylated liposomal doxorubicin
      (NPLD) may represent an attractive therapeutic option as salvage therapy for
      patients with metastatic breast cancer who have already received anthracycline
      based chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed 47
      consecutive patients with metastatic breast cancer treated with NPLD at our
      Institution between 2008 and 2012. Patients received weekly NPLD at a dose of 20
      mg/m(2) i.v. until disease progression or unacceptable toxicity. RESULTS: Nine
      patients (19.1%) achieved a partial response and 11 (23.4%) had stable disease,
      with a disease control rate of 42.6%; 27 patients (57.4%) had progressive
      disease. The median progression-free survival and overall survival were 2.7 and
      11.5 months, respectively. Grade 3 and 4 adverse events did not occur. No cardiac
      events were observed. CONCLUSION: Weekly NPLD represents a safe and effective
      therapy and may be considered a new therapeutic option for heavily pre-treated
      patients with metastatic breast cancer.

PMID- 24123038
TI  - Thymidylate synthase, topoisomerase-1 and microsatellite instability:
      relationship with outcome in mucinous colorectal cancer treated with
      fluorouracil.
AB  - BACKGROUND: Mucinous colorectal cancer (CRC) exhibits distinct clinical and
      pathological features, including poorer response to fluorouracil (FU) compared
      with non-mucinous tumours. PATIENTS AND METHODS: We compared the expression of
      thymidylate synthase (TYMS) and topoisomerase-1 (TOPO1) and DNA microsatellite
      instability (MSI) in 87 patients (35 mucinous and 52 non-mucinous CRCs) enrolled
      in three randomized trials, evaluating infused FU as first-line treatment.
      RESULTS: Mucinous CRCs more frequently had high TOPO1 expression than did non
      mucinous tumors (41% vs. 15%, p=0.028). The median overall survival was 14.2
      months for patients with mucinous CRC with low TOPO1 expression compared with 9.7
      months for high TOPO1-expressing cases (p=0.016). After adjusting for confounding
      variables, low TOPO1 expression was statistically favourably associated with
      overall survival (hazard ratio=0.55; p=0.041). CONCLUSION: Our data suggest the
      TOPO1 expression levels to be a prognostic marker in patients with mucinous CRC
      treated with FU. If further verified, these data might redefine therapeutic
      strategies by identifying categories of patients with a worse prognosis.

PMID- 24123039
TI  - Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in
      patients treated with sunitinib.
AB  - BACKGROUND/AIM: We analyzed the efficacy and toxicity profile of sunitinib
      according to single nucleotide polymorphisms (SNPs) of vascular endothelial
      growth factor receptor (VEGFR) and Kinase insert domain receptor (KDR). PATIENTS
      AND METHODS: We examined eight known SNPs of VEGFA and five SNPs of KDR among
      patients with gastric or biliary tract cancer who were treated with sunitinib. We
      retrospectively assessed clinical outcomes and their relationships to these SNPs.
      RESULTS: A total of 63 patients were evaluable. Among candidate SNPs, rs2010963
      and rs833068 of VEGFA, and rs1870377 of KDR were associated with poor time to
      treatment failure (TTF) (p=0.009, 0.002, and 0.029, respectively), while
      rs1870377 and rs7692791 of KDR were associated with poor overal survival (OS)
      (p=0.001 and 0.03, respectively). Multivariate analysis showed that only
      rs1870377 had significant effects on both TTF and OS. Toxicity evaluation
      indicated that rs1531289 of KDR was associated with grade 3-4 anemia. (p=0.021).
      CONCLUSION: Certain SNPs of KDR may affect treatment outcome and toxicity in
      patients treated with sunitinib.

PMID- 24123040
TI  - Oxaliplatin-based chemotherapy in patients aged 75 years or older with metastatic
      colorectal cancer.
AB  - AIM: To evaluate the tolerability and efficacy of oxaliplatin-based chemotherapy
      (OBC) in patients >= 75 years old with metastatic colorectal cancer (CRC).
      PATIENTS AND METHODS: We reviewed the medical records of 126 patients with
      unresectable stage IV CRC in terms of OBC administered as first-line chemotherapy
      whenever feasible. RESULTS: Use of first-line OBC was significantly less frequent
      in patients >= 75 years old (n=18) than in patients <75 years old (n=108) (46%
      vs. 81% p<0.01). When analysis was restricted to patients receiving OBC, the two
      age groups did not differ significantly in terms of response rate (44% vs. 36%,
      p=0.54), progression-free survival (18.7 months vs. 13.0 months, p=0.44), overall
      survival (25.4 months vs. 17.5 months, p=0.53), and frequency of grade 3-4
      toxicity (72% vs. 58%, p=0.26). CONCLUSION: In selected patients aged 75 years or
      greater, the clinical outcomes of OBC seem equivalent to those of younger
      patients.

PMID- 24123041
TI  - Carboplatin plus either docetaxel or paclitaxel for Japanese patients with
      advanced non-small cell lung cancer.
AB  - AIM: Assessment of the efficacy of docetaxel plus carboplatin vs. paclitaxel plus
      carboplatin in Japanese patients with advanced non-small cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomly assigned
      at a ratio of 2 to 1 to receive six cycles of either docetaxel (60 mg/m(2)) plus
      carboplatin [area under the curve (AUC)=6 mg/ml min] or paclitaxel (200 mg/m(2))
      plus carboplatin (same dose), on day 1 every 21 days. The primary end-point was
      progression-free survival (PFS). RESULTS: A total of 90 patients were enrolled.
      Overall response rate, median PFS and median survival time in the docetaxel-plus
      carboplatin group and the paclitaxel-plus-carboplatin group were 23% vs. 33%, 4.8
      months vs. 5.1 months, and 17.6 months vs. 15.6 months, respectively. The
      docetaxel-plus-carboplatin group had a higher incidence of grade 3 or 4
      neutropenia (88% vs. 60%). CONCLUSION: Both regimens were similarly effective in
      Japanese patients with advanced NSCLC.

PMID- 24123042
TI  - Image-guided stereotactic radiosurgery for cranial lesions: large margins
      compensate for reduced image guidance frequency.
AB  - BACKGROUND: We investigated patient positioning during radiosurgery of cranial
      lesions, and calculated clinical target volume (CTV) to planning target volume
      (PTV) margins using a modified common margin recipe. We simulated CTV-to-PTV
      margins for reduced image guidance, and repositioning for the first table angle
      only. PATIENTS AND METHODS: Patients were immobilized with a thermoplastic mask.
      Positioning was verified and corrected using the ExacTrac/Novalis Body. Each
      patient was repositioned before each beam. A common margin recipe was adapted for
      estimation of CTV-to-PTV margins. Necessary margins were estimated to correct
      positioning for the initial table angle only in comparison. RESULTS: In total,
      269 radiosurgery treatments with 967 different-angle setups (mean 3.6 different
      angles) were performed on 190 patients. Residual translational errors were (one
      standard deviation) 0.3 mm in left-right (LR), superior-inferior (SI), and
      anterior-posterior (AP) directions, with a mean three-dimensional vector of 0.5
      mm. Margins for residual errors after correction were calculated in LR, SI, and
      AP directions as 0.8 mm. For simulated reduced frequency setup correction, we
      calculated CTV-to-PTV margins as 1.9, 1.9, and 1.6 mm, respectively. CONCLUSIONS:
      The ExacTrac/Novalis Body system allows for accurate positioning of the patient
      with a residual error comparable to invasive mask fixation. If verification is
      only performed after initial positioning, adaption of CTV-to-PTV margins should
      be considered.

PMID- 24123043
TI  - Postoperative follow-up of patients with gastric cancer according to nodal
      status.
AB  - BACKGROUND: The aim of the present study was to determine the suitable
      postoperative management of patients with gastric cancer. PATIENTS AND METHODS: A
      total of 161 patients with gastric cancer who developed recurrence after curative
      resection were reviewed retrospectively to investigate the clinicopathological
      characteristics of recurrence in subgroups classified according to the Japanese
      Classification of Gastric Cancer (JCGC) staging system. RESULTS: Survival
      analysis of recurrent cases alone demonstrated significant differences in disease
      free survival (DFS) among groups according to the pN stage (p=0.0009); however,
      there was no significant difference among groups according to the pT stage
      (p=0.39). Eighty percent of recurrences developed within 32, 25, and 15 months in
      the N0, N1/2 and N3 groups, respectively. CONCLUSION: The present study
      demonstrated that DFS and post-recurrent survival significantly differed among
      groups according to pN stage. These findings may provide useful information for
      maximizing the efficiency of postoperative follow-up.

PMID- 24123044
TI  - Serum DNA hypermethylation in patients with kidney cancer: results of a
      prospective study.
AB  - AIM: No reliable biomarker for renal cell carcinoma (RCC) exists. The purpose of
      this study was to analyze the value of CpG island hypermethylation of cell-free
      (cf) circulating serum DNA in patients with RCC as a potential biomarker.
      PATIENTS AND METHODS: In total 35 patients with RCC and 54 healthy individuals
      were enrolled in this study. Cell-free DNA (cFDNA) in serum was isolated and
      digested with methylation-sensitive restriction enzymes (Bsh1236I, HpaII and
      HinP1I) to quantify the amount of methylated Adenomatosis-poliposis-coli gene
      (APC), Gluthation-a-transferase-protein 1 gene (GSTP1), ARF tumor suppressor
      protein gene (p14(ARF)), cyclin-dependent kinase inhibitor 2A (p16), Retinoid
      acid-receptor-beta gene (RAR-B), RAS-association domain family-1 gene (RASSF1),
      Tissue inhibitor of metalloproteinase-gene (TIMP3) and Prostaglandin-endoperoxid
      synthase 2 (PTGS2) DNA fragments. RESULTS: In 30 of 35 investigated patients with
      RCC, at least one gene was methylated within the serum cfDNA. The methylation
      frequency ranged from 14.3% for p14(ARF) to 54.3% for APC. All genes, except p16
      and TIMP3, were significantly more frequently methylated in patients with RCC
      compared to healthy individuals. Receiver operator characteristic analysis showed
      a high specificity for serum cfDNA methylation [between 85.2% for RAR-B and 100%
      for p14(ARF)], but the sensitivity was low in single-gene analysis [range-14.3%
      for p14(ARF) to 54.3% for APC]. The combined analysis of multiple genes increased
      the diagnostic sensitivity (i.e. APC, PTGS2 and GSTP1, 62.9%) at a high
      specificity (87%). DNA hypermethylation of APC was correlated with advanced tumor
      stage. CONCLUSION: The detection of hypermethylated cfDNA in serum may be helpful
      for the identification of RCC; the combinatorial analysis of multiple genes may
      increase the diagnostic accuracy.

PMID- 24123045
TI  - Biopsy and radical prostatectomy pathological patterns influence Prostate cancer
      gene 3 (PCA3) score.
AB  - AIM: To evaluate the relationship between Prostate cancer gene 3 (PCA3) score and
      prostate cancer as assessed by Gleason Score (GS) and pathological stage in a
      series of Italian patients, with elevated Prostate specific antigen (PSA)
      undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A total of 222
      patients underwent RP for clinically localized prostate cancer; total PSA, free
      PSA (%fPSA) and PCA3 score were collected and the possible associations among
      PCA3 and histological grade/pathological stage at biopsy and RP were
      investigated. RESULTS: Median PCA3 scores by GS at radical prostatectomy were 51
      vs. 67 (GS <7 vs. GS >= 7, p=0.007), while scores at the biopsy were 56 vs. 67
      (GS <7 vs. GS >= 7, p=0.007), and in pT2 vs. pT3 patients they were 54 vs. 80
      (p=0.001). Positive digital rectal examination (DRE) (odds ratio (OR)=5.47,
      p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 >= 35 (OR=2.04,
      p=0.030) were the main risk factors for the presence of an aggressive disease (GS
      >= 7 at RP). CONCLUSION: PCA3 score could play an interesting role in predicting
      significant disease: positive DRE (OR=5.47, p=0.026), pT3 pathological stage
      (OR=3.68, p=0.006) and PCA3 >= 35 (OR=2.04, p=0.030) were the main independent
      risk factors for GS >= 7 at RP.

PMID- 24123046
TI  - Outcome of allotransplants in patients with chronic-phase chronic myeloid
      leukemia following imatinib failure: prognosis revisited.
AB  - BACKGROUND: The outcome of allotransplants in patients with chronic -phase (CP)
      chronic myeloid leukemia (CML) who progressed to accelerated phase (AP) or blast
      phase (BP) following imatinib failure, especially those without preceding
      suboptimal response, remains unclear. PATIENTS AND METHODS: One hundred and five
      patients with newly-diagnosed CML-CP were retrospectively reviewed. Sixty-six
      patients received first-line imatinib therapy, 26 received interferon followed by
      imatinib, and 13 received front-line allotransplants. RESULTS: No significant
      differences were found in overall survival (p=0.57) and blast-free survival
      (p=0.25) between different first-line therapies. Among 66 imatinib-treated
      patients, 18 (27.3%) developed imatinib failure, 14 (21.2%) progressed to AP/BP,
      including eight without preceding suboptimal response. Compared to front-line
      allotransplant, patients with imatinib failure had a significantly worse overall
      survival after allotransplants (p=0.015), mainly due to an increase of treatment
      related mortality. CONCLUSION: Early recognition of imatinib-treated patients who
      should receive an allotransplant is important rather than waiting until imatinib
      failure with disease progression.

PMID- 24123047
TI  - Preserved renal function after percutaneous radiofrequency ablation for renal
      tumors: experience of a single institution.
AB  - BACKGROUND: Percutaneous radiofrequency ablation (RFA) for small renal tumors has
      been reported to be effective in patients with poor surgical status. We
      retrospectively analyzed clinical outcomes, including renal function, after RFA.
      PATIENTS AND METHODS: We retrospectively analyzed data of 24 patients with small
      renal tumors treated by RFA in our institution from January 2007 to November
      2012. RESULTS: A total of 36 tumors (35 renal cell carcinomas and one colon
      cancer metastasis) with a mean diameter of 21.1 mm (10-45 mm) in 24 patients were
      treated. Complete ablation was achieved in 22 patients (91.7%). There were two
      recurrences in other sites of the kidney (8.3%) and two distant metastases (8.3%)
      during the mean follow-up period of 21 months (1-57 months). No severe
      perioperative complications were observed. No significant difference in serum
      creatinine levels before and after RFA procedures in the 22 evaluable patients,
      nor in seven patients with a solitary kidney. CONCLUSION: RFA for small renal
      tumors is a safe treatment with sufficient preservation of renal function, even
      in patients with a solitary kidney.

PMID- 24123048
TI  - Platinum-based combination chemotherapy vs. weekly cisplatin during adjuvant CCRT
      in early cervical cancer with pelvic LN metastasis.
AB  - AIM: Adjuvant concurrent chemoradiation (CCRT) should be considered in surgically
      treated patients with early-stage cervical cancer (ECC) who exhibit pelvic lymph
      node (LN) metastasis. Platinum-based chemotherapy is usually recommended during
      adjuvant CCRT, however, it is unclear which regimen has better prognostic
      outcomes. PATIENTS AND METHODS: We reviewed the electronic medical records to
      find patients with primary ECC (FIGO stages IB-IIA) who underwent type III
      radical hysterectomy and adjuvant CCRT due to pelvic LN metastasis at the Samsung
      Medical Center, Sungkyunkwan University School of Medicine in Seoul, Korea, from
      November 1997 to September 2007. RESULTS: Among 75 patients, 34 received weekly
      cisplatin. Combination chemotherapy was performed without consolidation in 21
      patients and with consolidation in 20 patients. The mean follow-up period was
      59.0 months and the five-year survival rate was 84.4%. In multivariate analysis,
      combination chemotherapy with and without consolidation was associated with
      improved disease-free survival [hazard ratio (HR)=0.23, 95% confidence interval
      (CI)=0.06-0.88, p=0.032, and HR=0.29, 95% CI=0.09-0.91, p=0.034, respectively];
      combination chemotherapy with consolidation significantly improved overall
      survival (HR=0.11, 95% CI=0.02-0.87, p=0.037) when compared to weekly cisplatin.
      CONCLUSION: We found that platinum-based combination chemotherapy during adjuvant
      CCRT after surgery promoted better survival than a weekly cisplatin regimen in
      ECC patients with pelvic LN metastasis.

PMID- 24123049
TI  - A model for repeated clustered data with informative cluster sizes.
AB  - Many chronic diseases or health conditions manifest with recurring episodes, each
      of which can be characterized by a measure of intensity or severity. Both the
      number of episodes and the severity of each episode can depend on the latent
      severity of an individual's underlying condition. Data such as this are commonly
      gathered repeatedly at fixed follow-up intervals. An example is a study of the
      association between stressful life events and the onset of depression. Stress
      exposure is assessed through the frequency and intensity of stressful life events
      occurring each month. Both the number of events and the intensity of each event
      at each measurement occasion are informative about the underlying severity of
      stress over time. One might hypothesize that people that approach the onset of a
      depressive episode have worse stress profiles than the controls, reflected by
      both more frequent and more intense stressors. We propose models to analyze data
      collected repeatedly on both the frequency of an event and its severity when both
      of these are informative about the underlying latent severity. Maximum likelihood
      estimators are developed, and simulations with small to moderate sample sizes
      show that the estimators also have good finite sample properties, and they are
      robust against misspecification of the model. This method is applied to a
      psychiatric data set.

PMID- 24123050
TI  - TEG and ROTEM: technology and clinical applications.
AB  - Initially described in 1948 by Hertert thromboelastography (TEG) provides a real
      time assessment of viscoelastic clot strength in whole blood. Rotational
      thromboelastometry (ROTEM) evolved from TEG technology and both devices generate
      output by transducing changes in the viscoelastic strength of a small sample of
      clotting blood (300 ul) to which a constant rotational force is applied. These
      point of care devices allow visual assessment of blood coagulation from clot
      formation, through propagation, and stabilization, until clot dissolution.
      Computer analysis of the output allows sophisticated clot formation/dissolution
      kinetics and clot strength data to be generated. Activation of clot formation can
      be initiated with both intrinsic (kaolin, ellagic acid) and extrinsic (tissue
      factor) activators. In addition, the independent contributions of platelets and
      fibrinogen to final clot strength can be assessed using added platelet inhibitors
      (abciximab and cytochalasin D). Increasingly, ROTEM and TEG analysis is being
      incorporated in vertical algorithms to diagnose and treat bleeding in high-risk
      populations such as those undergoing cardiac surgery or suffering from blunt
      trauma. Some evidence suggests these algorithms might reduce transfusions, but
      further study is needed to assess patient outcomes.

PMID- 24123051
TI  - Protein expression profiling during wallerian degeneration after rat sciatic
      nerve injury.
AB  - INTRODUCTION: Wallerian degeneration (WD) is an important area of research in
      modern neuroscience. Many protein expressions are regulated by differentially
      expressed genes in WD, but the precise mechanisms are elusive. METHODS: In this
      study, we profiled differentially expressed proteins in WD after rat sciatic
      nerve injury using an antibody array. RESULTS: Functional analysis positively
      identified cell proliferation, regulation of cell proliferation, and immune
      system processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis
      revealed molecular networks related mainly to cytokine-cytokine receptor
      interaction, the mitogen-activated proteinkinase (MAPK) signaling pathway,
      apoptosis, the toll-like receptor (TLR) signaling pathway, and the Janus kinase
      (Jak) - signal transducer and activator of transcription (STAT) signaling
      pathway. Interactions between these differential proteins were well established
      and regulated by the key factors transforming growth factor beta 1 (TGF-beta1),
      toll-like receptor 4 (TLR4), Fas ligand (FasL), and 5'-AMP-activated protein
      kinase catalytic subunit alpha-1 (PRKAA1). CONCLUSIONS: These results provide
      information related to functional analysis of differentially expressed genes
      during WD.

PMID- 24123052
TI  - Expression of the cancer-testis antigen BORIS correlates with prostate cancer.
AB  - BACKGROUND: BORIS, a paralogue of the transcription factor CTCF, is a member of
      the cancer-testis antigen (CT) family. BORIS is normally present at high levels
      in the testis; however it is aberrantly expressed in various tumors and cancer
      cell lines. The main objectives of this study were to investigate BORIS
      expression together with sub-cellular localization in both prostate cell lines
      and tumor tissues, and assess correlations between BORIS and
      clinical/pathological characteristics. METHODS: We examined BORIS mRNA
      expression, protein levels and cellular localization in a panel of human prostate
      tissues, cancer and benign, together with a panel prostate cell lines. We also
      compared BORIS levels and localization with clinical/pathological characteristics
      in prostate tumors. RESULTS: BORIS was detected in all inspected prostate cancer
      cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased
      levels of BORIS protein positively correlated with Gleason score, T-stage and
      androgen receptor (AR) protein levels in prostate tumors. The relationship
      between BORIS and AR was further highlighted in prostate cell lines by the
      ability of ectopically expressed BORIS to activate the endogenous AR mRNA and
      protein. BORIS localization in the nucleus plus cytoplasm was also associated
      with higher BORIS levels and Gleason score. CONCLUSIONS: Detection of BORIS in
      prostate tumors suggests potential applications of BORIS as a biomarker for
      prostate cancer diagnosis, as an immunotherapy target and, potentially, a
      prognostic marker of more aggressive prostate cancer. The ability of BORIS to
      activate the AR gene indicates BORIS involvement in the growth and development of
      prostate tumors.

PMID- 24123053
TI  - A canonical EF-loop directs Ca(2+) -sensitivity in phospholipase C-eta2.
AB  - Phospholipase C-eta (PLCeta) enzymes are a class of phosphatidylinositol 4,5
      bisphosphate-hydrolyzing enzymes involved in intracellular signaling. PLCeta2 can
      sense Ca(2+) (stimulated by ~1 uM free Ca(2+) ) suggesting that it can amplify
      transient Ca(2+) signals. PLCeta enzymes possess an EF-hand domain composed of
      two EF-loops; a canonical 12-residue loop (EF-loop 1) and a non-canonical 13
      residue loop (EF-loop 2). Ca(2+) -binding to synthetic peptides corresponding to
      EF-loops 1 and 2 of PLCeta2 and EF-loop 1 of calmodulin (as a control) was
      examined by 2D-[(1) H,(1) H] TOCSY NMR. Both PLCeta2 EF-loop peptides bound
      Ca(2+) in a similar manner to that of the canonical calmodulin EF-loop 1,
      particularly at their N-terminus. A molecular model of the PLCeta2 EF-hand
      domain, constructed based upon the structure of calmodulin, suggested both EF
      loops may participate in Ca(2+) -binding. To determine whether the EF-hand is
      responsible for Ca(2+) -sensing, inositol phosphate accumulation was measured in
      COS7 cells transiently expressing wild-type or mutant PLCeta2 proteins. Addition
      of 70 uM monensin (a Na(+) /H(+) antiporter that increases intracellular Ca(2+) )
      induced a 4- to 7-fold increase in wild-type PLCeta2 activity. In permeabilized
      cells, PLCeta2 exhibited a ~4-fold increase in activity in the presence of 1 uM
      free Ca(2+) . The D256A (EF-loop1) mutant exhibited a ~10-fold reduction in
      Ca(2+) -sensitivity and was not activated by monensin, highlighting the
      involvement of EF-loop 1 in Ca(2+) -sensing. Involvement of EF-loop 2 was
      examined using D292A, H296A, Q297A, and E304A mutants. Interestingly, the
      monensin responses and Ca(2+) -sensitivities were largely unaffected by the
      mutations, indicating that the non-canonical EF-loop 2 is not involved in Ca(2+) 
      sensing.

PMID- 24123054
TI  - Human caliciviruses detected in HIV-seropositive children in Kenya.
AB  - The human caliciviruses (HuCVs) are important causes of gastroenteritis
      worldwide. Norovirus (NoV) and sapovirus (SaV) have been detected in HIV
      seropositive children but the genetic diversity of HuCVs circulating in these
      individuals is largely unknown. In this study the prevalence and genotype
      diversity of HuCVs circulating in Kenyan HIV-positive children, with or without
      diarrhea, from the year 1999 to 2000 was investigated. The overall prevalence of
      HuCVs was 19% with NoV predominating at 17% (18/105) and SaV present in 5.7%
      (6/105) of specimens. Human CVs were detected in both symptomatic (24%) and
      asymptomatic (16%) children. Co-infections with other enteric viruses were
      detected in 21.6% of children with diarrhea but only in 4.4% of children without
      diarrhea. Remarkable genetic diversity was observed with 12 genotypes (7 NoV, 5
      SaV) being identified in 20 HuCV-infected children. NoV genogroup II (GII)
      strains predominated with GII.2 and GII.4 each representing 27% of the NoV
      positive strains. The GII.4 strain was most closely related to the nonepidemic
      GII.4 Kaiso 2003 variant. Other NoV genotypes detected were GI.3, GII.6, GII.12,
      GII.14, and GII.17. Five different SaV genotypes (GI.2, GI.6, GII.1, GII.2, and
      GII.4) were characterized from six specimens. Diarrheal symptoms were not
      associated with any specific HuCV genotype. Overall the HuCV genotype
      distribution detected in this study reflects those in other studies worldwide.
      The strains detected are closely related to genotypes that have circulated on
      several continents since the year 2000.

PMID- 24123055
TI  - Electrolyte system strategies for anionic isotachophoresis with electrospray
      ionization mass-spectrometric detection. 2. Isotachophoresis in moving-boundary
      systems.
AB  - This contribution is the second part of the project on strategies used in the
      selection of electrolyte systems for anionic ITP with ESI-mass spectrometric
      detection. It presents ITP as a powerful tool for selective stacking of anionic
      analytes, performed in a nonconventional way in moving-boundary systems where two
      co-anions are present in both the leading and terminating zones. The theoretical
      background is given to substantiate the conditions for the existence and
      migration of ITP boundaries in moving-boundary systems and stacking of analytes
      at these boundaries. The practical aspects of the theory are shown in form of
      stacking-window diagrams that bring immediate information about which analytes
      are stacked in a given system. The presented theory and strategy are illustrated
      and verified on the example of analysis of a model mixture of salicylic acid,
      ibuprofen and diclofenac, and comparison of regular and free-acid ITP with moving
      boundary ITP systems formed by formic and propionic acids and ammonium as
      counterion. 

PMID- 24123056
TI  - Adjuvant stereotactic body radiotherapy+/-cetuximab following salvage surgery in
      previously irradiated head and neck cancer.
AB  - OBJECTIVES/HYPOTHESIS: Locoregional recurrence remains the primary failure
      pattern following salvage surgery for previously irradiated head and neck cancer;
      randomized trials have suggested a complimentary role for adjuvant chemotherapy
      and conventional reirradiation at the expense of significant increases in
      toxicity. We aimed to identify if stereotactic body radiotherapy (SBRT) +/-
      cetuximab improves tumor control while reducing treatment-related toxicity
      following salvage surgery. STUDY DESIGN: Retrospective review (2005-2011) of 28
      patients with high-risk features (positive surgical margins or extranodal
      extension) following macroscopic complete (R0/R1) salvage surgery treated with
      adjuvant SBRT+/-cetuximab. METHODS: SBRT consisted of 40 to 44 Gy in five
      fractions over 1 to 2 weeks with concurrent cetuximab (n=7) administered at 400
      mg/m2 day -7+250 mg/m2 days 0 and +8. Toxicity was physician recorded, and
      University of Washington Quality of Life Revised surveys were prospectively
      collected. RESULTS: All patients received prior radiotherapy (median, 70 Gy;
      range, 54-99 Gy) with a median reirradiation interval of 25 months (range, 6-156
      months). At a median follow-up of 14 months (range, 2-69 months), the 1-year
      locoregional control, distant control, disease-free survival, and overall
      survival were 51%, 90%, 49%, and 64%, respectively. Rates of acute and late
      severe (>=grade 3) toxicity were low at 0% and 8%, respectively. At a median
      follow-up survey time of 6 months, 56% of patients reported improved/stable
      overall quality-of-life scores. CONCLUSIONS: Adjuvant SBRT+/-cetuximab following
      salvage surgery is well tolerated with acceptable oncologic outcomes and little
      toxicity. Future prospective trials should evaluate adjuvant SBRT+/-cetuximab
      versus a wait-and-see approach for recurrent head and neck cancers with high-risk
      features following salvage surgery. LEVEL OF EVIDENCE: 4.

PMID- 24123057
TI  - The function of Msx1 gene in promoting meiosis of dairy goat male germline stem
      cells (mGSCs).
AB  - During sequential stages of meiosis, numerous cytoplasmic and nuclear events take
      place in which many germline and non-germline genes involved. It is demonstrated
      that the germline gene Stra8 and synaptonemal complex protein 3 (Scp3) play an
      important role in the meiosis. Recently, studies showed Msx1, a DNA-binding
      protein taking part in the skeletal development, also having a functional
      attractive factor to Stra8 and Scp3 in the meiosis. In this study, we cloned the
      gene Msx1 then transfected the Msx1 constructed recombination plasmid, pMsx1
      Ires2-AcGFP, into the dairy goat germline stem cells (male germline stem cells)
      and analysed the effects of Msx1 on the expression of Stra8 and Scp3. The results
      showed that Msx1 could enhance the expression of Stra8 and Scp3 and promote the
      meiosis in goat testicular cells. Bmp4 activated the expression of Msx1 and
      Stra8. This study suggests that Msx1 plays an important role in spermatogenesis
      and meiosis.

PMID- 24123058
TI  - Localized spatio-temporal constraints for accelerated CMR perfusion.
AB  - PURPOSE: To develop and evaluate an image reconstruction technique for cardiac
      MRI (CMR) perfusion that uses localized spatio-temporal constraints. METHODS: CMR
      perfusion plays an important role in detecting myocardial ischemia in patients
      with coronary artery disease. Breath-hold k-t-based image acceleration techniques
      are typically used in CMR perfusion for superior spatial/temporal resolution and
      improved coverage. In this study, we propose a novel compressed sensing-based
      image reconstruction technique for CMR perfusion, with applicability to free
      breathing examinations. This technique uses local spatio-temporal constraints by
      regularizing image patches across a small number of dynamics. The technique was
      compared with conventional dynamic-by-dynamic reconstruction, and sparsity
      regularization using a temporal principal-component (pc) basis, as well as zero
      filled data in multislice two-dimensional (2D) and three-dimensional (3D) CMR
      perfusion. Qualitative image scores were used (1 = poor, 4 = excellent) to
      evaluate the technique in 3D perfusion in 10 patients and five healthy subjects.
      On four healthy subjects, the proposed technique was also compared with a breath
      hold multislice 2D acquisition with parallel imaging in terms of signal intensity
      curves. RESULTS: The proposed technique produced images that were superior in
      terms of spatial and temporal blurring compared with the other techniques, even
      in free-breathing datasets. The image scores indicated a significant improvement
      compared with other techniques in 3D perfusion (x-pc regularization, 2.8 +/- 0.5
      versus 2.3 +/- 0.5; dynamic-by-dynamic, 1.7 +/- 0.5; zero-filled, 1.1 +/- 0.2).
      Signal intensity curves indicate similar dynamics of uptake between the proposed
      method with 3D acquisition and the breath-hold multislice 2D acquisition with
      parallel imaging. CONCLUSION: The proposed reconstruction uses sparsity
      regularization based on localized information in both spatial and temporal
      domains for highly accelerated CMR perfusion with potential use in free-breathing
      3D acquisitions.

PMID- 24123059
TI  - Sex differences in the pharmacokinetics and bioequivalence of the delayed-release
      combination of doxylamine succinate-pyridoxine hydrochloride; implications for
      pharmacotherapy in pregnancy.
AB  - Most bioequivalence (BE) studies are conducted in males with the assumption that
      variability in pharmacokinetics is similar between the sexes. The purpose of this
      single-center, reference replicate study was to determine the effect of sex on
      the pharmacokinetics and BE of doxylamine-pyridoxine 10 mg-10 mg delayed-release
      tablets. Healthy males (n = 12) and non-pregnant females (n = 12) were
      administered two tablets, and blood sampling was conducted from 1 hour pre-dose
      until 72 hours post-dose. After 21 days, dose administration and blood sampling
      were re-conducted. All analytes were measured using liquid chromatography-tandem
      mass-spectrometry. Pharmacokinetic parameters were calculated for each study
      period using standard, non-compartmental methods, and differences were assessed
      using ANOVA. BE testing was conducted using the relative 90% confidence interval
      for the AUC0-t for each analyte. Females had significantly larger AUC0-t for
      doxylamine, 1,550 ng h/mL (coefficient of variance [CV = 19%]) versus 1,272 ng
      h/mL (CV = 21%; P <= .05), and pyridoxine, 35 ng h/mL, (CV = 43%) versus 25 ng
      h/mL (CV = 31%; P <= .05) compared to males. A higher Cmax for doxylamine was
      observed in females, 107 ng/mL (CV = 16%), compared to males, 86 ng/mL (CV = 15%)
      (P <= .05). BE testing did not demonstrate bioequivalence between males and
      females. Pharmacokinetic differences observed between the sexes have implications
      for future BE studies using doxylamine-pyridoxine. 

PMID- 24123060
TI  - Virtual CT sonographically guided biopsy of a retroperitoneal mass in a patient
      with Erdheim-Chester disease.
AB  - Image fusion between sonography and CT allows real-time synchronization of CT
      multiplanar reconstructed images with the corresponding sonographic images. This
      technique has mainly been used in liver imaging. We report the use of image
      fusion to target and successfully guide the percutaneous biopsy of a
      retroperitoneal a mass. This technique represents a promising tool in abdominal
      imaging, and it should be considered for the biopsy of lesions that are difficult
      to approach with conventional imaging guidance techniques.

PMID- 24123061
TI  - Local knowledge and perceptions of chimpanzees in Cantanhez National Park, Guinea
      Bissau.
AB  - Our study concerns local knowledge and perceptions of chimpanzees among farming
      communities within Cantanhez National Park, Guinea-Bissau. We submitted a survey
      questionnaire to 100 people living in four villages in the Park to enquire about
      their knowledge of chimpanzee ecology and human-chimpanzee interactions. Local
      farmers live in close contact with chimpanzees, consider them to be more similar
      to humans than any other species, and attribute special importance to them
      primarily due to expectations of tourism revenue. Interviewees' responses, as a
      function of gender, village, and age, were analyzed statistically using non
      parametric tests (Mann-Whitney and Kruskal-Wallis). Age influenced responses
      significantly, while gender and village had no significant effect. Youngsters
      emphasized morphological aspects of human-chimpanzee similarities, while adults
      emphasized chimpanzee behavior and narratives about the shared history of humans
      and chimpanzees. Tourism, conservation, and crop raiding feature prominently in
      people's reports about chimpanzees. Local people's engagement with conservation
      and tourism-related activities is likely to allow them to manage not only the
      costs but also the benefits of conservation, and can in turn inform the
      expectations built upon tourism.

PMID- 24123062
TI  - SPLIT rectus abdominis myocutaneous double free flap for extremity
      reconstruction.
AB  - A Mathes and Nahai type III muscle, such as the rectus abdominis muscle, can be
      utilized to cover two separate wounds simultaneously utilizing its dual blood
      supply thereby minimizing donor site morbidity and operative time. We report a
      case for treatment of bilateral Gustillo type IIIB lower extremity injuries
      treated with a single rectus abdominis muscle split into two free flaps, with one
      based on the deep inferior epigastric vessels and one on the superior epigastric
      vessels to cover the contralateral wound. In our patient, both lower extremity
      wounds were covered with muscle flaps from the same donor site in a single
      operation, salvaging both limbs with progression to unassisted ambulatory status.
      We show in this case report that the utilization of the vascular anatomy of the
      rectus muscle allows for division of the flap into two flaps, permitting
      preservation of the contralateral abdominal wall integrity and coverage of two
      wounds with a single muscle.

PMID- 24123063
TI  - Molecular detection of BRAF-V600E is superior to flow cytometry for disease
      evaluation in hairy cell leukaemia.

PMID- 24123064
TI  - Fractionated ablative carbon dioxide laser for the treatment of rhinophyma.
AB  - BACKGROUND: Rhinophyma is a progressive and disfiguring proliferative disorder of
      the nose, which is related to chronic rosacea. Many different treatment
      modalities have been utilized both alone and in combination including: loop
      cautery, CO2 laser, argon laser, dermabrasion, cryotherapy, radiotherapy, full
      thickness excision, skin graft, flap reconstruction, and cold scalpel. CO2
      resurfacing has been considered first line therapy but is often associated with a
      shiny, scarred appearance, with patulous pores, and with loss of pigmentation. We
      report a technique using aggressive parameters with the fractionated ablative CO2
      laser, resulting in improvement of appearance with very few complications.
      MATERIALS AND METHODS: Five patients who presented with rhinophyma of varying
      degrees were treated with a series of fractional ablative CO2 laser treatments
      (Fraxel re:Pair, Solta Medical, Hayward, CA). These patients were treated with
      settings of up to 70 mJ, 70% density and 16-18 passes. All patients received HSV
      prophylaxis using either acyclovir 400 mg TID or valacyclovir 500 mg BID.
      Patients were rendered anesthetic by 1% lidocaine and epinephrine regional
      perinasal nerve block. RESULTS: All of the patients tolerated the procedure well
      with reepithelialization at days 4-7 and self-limited edema and erythema.
      Patients with relatively early to moderate signs of rhinophyma proved optimal
      candidates for this treatment. There were no adverse events. Patients and
      physicians noted significant improvement and reduction in the rhinophyma without
      the typical scarring noted with most other treatments. CONCLUSION: Rhinophyma
      treated with fractionated ablative CO2 laser using relatively aggressive
      parameters achieved good cosmetic outcomes in this group of early to moderate
      cases of rhinophyma, while still retaining the benefits of a fractionated
      treatment such as faster healing times and fewer adverse events.

PMID- 24123065
TI  - Lipid utilization in radish seedlings as affected by weak horizontal extremely
      low frequency magnetic field.
AB  - Composition and content of lipids were studied in 5-day-old radish seedlings
      (Raphanus sativus L. var. radicula DC.) grown in lowlight and darkness in an
      extremely low frequency (ELF) magnetic field characterized by 50 Hz frequency and
      ~500 uT flux density. The control seedlings were grown under the same conditions,
      but without exposure to the magnetic field. The products of lipid metabolism were
      compared with lipid composition in seeds. In control seedlings, reserve neutral
      lipids, mostly triacylglycerides, were utilized for the formation of polar lipids
      (PL). As a result, the amount of the latter doubled, particularly due to
      glycolipids (GL) and phospholipids (PhL) compared to their content in seeds. At
      20-22  degrees C in light, magnetic field exposure increased the production of PL
      by threefold specifically, GL content increased fourfold and PhL content rose 2.5
      times, compared to seeds. In darkness, the effect of magnetic field on lipids was
      weaker. At the lower temperature of 13-16  degrees C in light, the effect of the
      magnetic field was weak, but in the darkness, no magnetic field action was
      recorded. It is concluded that ELF magnetic field stimulated lipid synthesis in
      chloroplast, mitochondrial, and other cell membranes in radish seedlings grown in
      light at 20-22  degrees C and 13-16  degrees C.

PMID- 24123066
TI  - Nerve ultrasound findings in two cases of spinal accessory nerve palsy.

PMID- 24123067
TI  - Age, rate of change in neuropathology, and trajectory of cognitive decline.

PMID- 24123068
TI  - Treatment with bortezomib-based regimens improves overall response and predicts
      for survival in patients with primary or secondary plasma cell leukemia: Analysis
      of the Greek myeloma study group.
AB  - Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with
      poor outcome. Bortezomib-based regimens (BBR) are highly effective in myeloma,
      but there is limited information about their efficacy and safety in PCL. Thus, we
      retrospectively collected data from 42 consecutive PCL patients (25 with primary
      PCL-pPCL and 17 with secondary PCL-sPCL) to explore the role of BBR in this
      entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with
      pPCL underwent autologous transplantation. Objective response (>=partial
      response) was significantly higher in patients treated with BBR versus
      conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with
      BBR achieved at least very good partial response (vgPR). The highest ORR was
      observed in pPCL patients treated with BBR (88.9%; >=vgPR: 33.3%). In BBR-group,
      grade 3 of 4 hematological, neurological and renal toxicity and neutropenic
      infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median
      follow-up of 51 months, median overall survival (OS) for patients treated with
      BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS
      of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively
      (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and
      high quality response were the only powerful predictors for survival. Our study
      carrying the longest reported median follow-up, demonstrated that treatment of
      PCL with BBR induces high response rates and prolongs survival over conventional
      therapies, regardless of additional autologous transplantation rescue or
      established high risk features, with manageable toxicity.

PMID- 24123069
TI  - Joint confidence region estimation for area under ROC curve and Youden index.
AB  - In the field of diagnostic studies, the area under the ROC curve (AUC) serves as
      an overall measure of a biomarker/diagnostic test's accuracy. Youden index,
      defined as the overall correct classification rate minus one at the optimal cut
      off point, is another popular index. For continuous biomarkers of binary disease
      status, although researchers mainly evaluate the diagnostic accuracy using AUC,
      for the purpose of making diagnosis, Youden index provides an important and
      direct measure of the diagnostic accuracy at the optimal threshold and hence
      should be taken into consideration in addition to AUC. Furthermore, AUC and
      Youden index are generally correlated. In this paper, we initiate the idea of
      evaluating diagnostic accuracy based on AUC and Youden index simultaneously. As
      the first step toward this direction, this paper only focuses on the confidence
      region estimation of AUC and Youden index for a single marker. We present both
      parametric and non-parametric approaches for estimating joint confidence region
      of AUC and Youden index. We carry out extensive simulation study to evaluate the
      performance of the proposed methods. In the end, we apply the proposed methods to
      a real data set.

PMID- 24123070
TI  - Multiplex ligase-based genotyping methods combined with CE.
AB  - In this genomic era, the ability to assay multiple genomic hot spots that have
      strong clinical implications is greatly desired. Conventional PCR-based methods
      suffer from frequent false-positive detections, particularly when a multiplex
      analysis is desirable. As an alternative to the error-prone conventional methods,
      multiplex ligase-based genotyping methods combined with CE have a strong
      potential. In this review, both previously developed methods and emerging methods
      are described to reveal the specificity, sensitivity, and simplicity of the
      ligase-based methods. For each step (ligation, amplification, and separation),
      the principles of several alternative methods are discussed along with their
      applications to explore the future development of ligase-based diagnostic
      methods.

PMID- 24123071
TI  - Osteoblast adhesion dynamics: a possible role for ROS and LMW-PTP.
AB  - Reactive oxygen species (ROS) modulate a variety of intracellular events, but
      their role in osteoblast adhesion and spreading remains unclear. ROS is a very
      known physiological modulators of Protein Tyrosine Phosphatases activities,
      mainly to low molecular weight protein tyrosine phosphatase (LMW-PTP) activity.
      As this biological mechanism is not clear in osteoblast adhesion, we decided to
      investigate ROS levels and phosphorylations of FAK and Src, identifying these
      proteins as potential substrates to LMW-PTP activity. Our results showed that
      during osteoblast adhesion/spreading (30 min and 2 h of seeding) the
      intracellular ROS content (hydrogen peroxide) is finely regulated by an effective
      anti-oxidant system [catalase and Superoxide Dismutase (SOD) activities were
      evaluated]. During the first 30 min of adhesion, there was an increase in ROS
      production and a concomitant increase in focal adhesion kinase (FAK) activity
      after its phosphorylation at Tyrosine 397 (Y397 ). Moreover, after 2 h there was
      a decrease in ROS content and FAK phosphorylation. There was no significant
      change in LMW-PTP expression at 30 min or 2 h. In order to validate our
      hypothesis that LMW-PTP is able to control FAK activity by modulating its
      phosphorylation status, we decided to overexpress and silence LMW-PTP in this
      context. Our results showed that FAK phosphorylation at Y397 was increased and
      decreased in osteoblasts with silenced or overexpressed LMW-PTP, respectively.
      Together, these data show that ROS modulate FAK phosphorylation by an indirect
      way, suggesting that a LMW-PTP/FAK supra-molecular complex is involved in
      transient responses during osteoblast adhesion and spreading.

PMID- 24123072
TI  - Human bocavirus in children with acute respiratory infections in Vietnam.
AB  - Acute respiratory infections are the major cause of morbidity and mortality
      globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly
      associate with previously unknown etiology respiratory infections in young
      children. In this study, the epidemiological, clinical, and molecular
      characteristics of HBoV infections were described in hospitalized Vietnamese
      pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab
      samples were obtained from patients with acute respiratory infections at the
      Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV
      by PCR and further molecularly characterized by sequencing. HBoV was found in 78
      (7.2%) children. Co-infection with other viruses was observed in 66.7% of
      patients infected with HBoV. Children 12-24 months old were the most affected age
      group. Infections with HBoV were found year-round, though most cases occurred in
      the dry season (December-April). HBoV was possible to cause severe diseases as
      determined by higher rates of hypoxia, pneumonia, and longer hospitalization
      duration in patients with HBoV infection than in those without (P-value <0.05).
      Co-infection with HBoV did not affect the disease severity. The phylogenetic
      analysis of partial VP1 gene showed minor variations and all HBoV sequences
      belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam
      and detected frequently in young children during dry season. Acute respiratory
      infections caused by HBoV1 were severe enough for hospitalization, which implied
      that HBoV1 may have an important role in acute respiratory infections among
      children.

PMID- 24123073
TI  - How sweet it is to activate FXR.

PMID- 24123078
TI  - Truncus bicaroticus: an underestimated anatomic variation.
AB  - OBJECTIVES/HYPOTHESIS: To illustrate that a truncus bicaroticus and an elongated
      truncus brachiocephalicus are underestimated anatomic variations; and to
      highlight the risk of injury of these vessel anomalies during routine surgical
      interventions. DATA SOURCE: Report of a woman with long-term ventilation who was
      planned for conventional surgical tracheostomy. Due to a strong pulsatile vessel
      crossing the cricoid cartilage, the procedure was stopped. Further diagnostics
      revealed anomalies of the supraaortic vessels, including a truncus bicaroticus.
      CONCLUSION: Anomalies of supraaortic vessels are not rare and injuries may cause
      severe bleeding; therefore, we recommend performing a preoperative ultrasound,
      particularly before starting dilatative tracheostomy.

PMID- 24123079
TI  - Absolute magnetic susceptibility of rat brain tissue.
AB  - PURPOSE: This study was performed to test the commonly held hypothesis that the
      absolute magnetic susceptibility of brain tissue is close to that of water since
      water accounts for over 50% of the tissue composition. In addition, the absolute
      value of susceptibility of brain tissue is needed for the development of
      materials that are implanted into or in close proximity to tissue. METHODS: The
      absolute magnetic susceptibilities of different sections of rat brain, which were
      exsanguinated and perfusion-fixed, have been measured in a commercial
      superconducting quantum interference device magnetometer operating in fields up
      to 7T. RESULTS: The average measured values ranged from -(9.51 +/- 0.01) * 10(-6)
      for the cerebellum to -(8.99 +/- 0.01) * 10(-6) for a mixture of hippocampus,
      corpus callosum, and striatum. The time evolution of the samples was also
      studied, and deviations of <1% were observed after 4 weeks, although this trend
      was sample-specific. CONCLUSION: The measured susceptibilities are close to the
      value measured for high-performance liquid chromatography H2 O and depend on the
      amount of gray and white matter regions present in the samples.

PMID- 24123080
TI  - Continuous exposure to 60 Hz magnetic fields induces duration- and dose-dependent
      apoptosis of testicular germ cells.
AB  - To evaluate duration- and dose-dependent effects of continuous exposure to a 60
      Hz magnetic field (MF) on the testes in mice, BALB/c male mice were exposed to a
      60 Hz MF at 100 MUT for 24 h a day for 2, 4, 6, or 8 weeks, and at 2, 20, or 200
      MUT for 24 h a day for 8 weeks. Any exposures to MF did not significantly affect
      body or testicular masses. However, the apoptotic cells among testicular germ
      cells were increased duration-dependent at exposures of 100 MUT for 6 and 8 weeks
      and dose-dependent at exposures of 20 and 200 MUT for 8 weeks. The number of
      sperm in epididymis and the diameter of seminiferous tubule decreased in mice
      exposed to 100 and 200 MUT for 8 weeks, respectively. To induce the apoptosis of
      testicular germ cell in mice, the minimum dose is 20 MUT at continuous exposure
      to a 60 Hz MF for 8 weeks and the minimum duration is 6 weeks at continuous
      exposure of 100 MUT. Taken together, these results suggest that continuous
      exposure to a 60 Hz MF might affect, duration- and dose-dependent biological
      processes including apoptotic cell death and spermatogenesis in the male
      reproductive system of mice.

PMID- 24123081
TI  - Validation of Western common recurrent chromosomal aberrations in Korean chronic
      lymphocytic leukaemia patients with very low incidence.
AB  - In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in
      Western countries. Only a few studies of CLL have been conducted in Korea, and no
      long-term clinical outcome data are available. We assessed the frequency of
      common chromosomal aberrations in Korean CLL patients using interphase
      fluorescence in situ hybridization (FISH) and investigated their relationship to
      clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were
      performed in 58 patients, and FISH results were available in 48 patients. We used
      six DNA probes for the detection of del(13q14), trisomy 12, del(11q22),
      del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were
      identified in 15 of 58 patients (26%) with conventional cytogenetic studies and
      in 25 of 48 patients (52%) with interphase FISH, including six patients with
      complex karyotypes. In contrast with the results of Western studies, trisomy 12
      was the most common aberration, followed by IGH rearrangement, del(13q14),
      del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated
      del(13q14) was less frequent than in Western studies. Compared with the other
      types of chromosomal aberrations, patients with del(11q22) and del(17p13) were
      more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to
      chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and
      isolated del(13q14) showed better responses and superior survival outcomes. The
      incidence of CLL is lower in Korea than in Western countries, and the frequency
      of chromosomal aberrations differs, perhaps reflecting differences in the
      pathogenic mechanism between ethnicities. Large prospective studies are needed to
      further assess the prognostic value of these results in Korean CLL patients.

PMID- 24123082
TI  - Author reply: To PMID 23666793.

PMID- 24123083
TI  - Human behavior and opportunities for parasite transmission in communities
      surrounding long-tailed macaque populations in Bali, Indonesia.
AB  - Spatial overlap and shared resources between humans and wildlife can exacerbate
      parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious
      temple system provides sanctuaries for long-tailed macaques (Macaca
      fascicularis), concentrating them in areas in close proximity to humans. In this
      study, we interviewed individuals in communities surrounding 13 macaque
      populations about their willingness to participate in behaviors that would put
      them at risk of exposure to gastrointestinal parasites to understand if age,
      education level, or occupation are significant determinants of exposure
      behaviors. These exposure risk behaviors and attitudes include fear of macaques,
      direct contact with macaques, owning pet macaques, hunting and eating macaques,
      and overlapping water uses. We find that willingness to participate in exposure
      risk behaviors are correlated with an individual's occupation, age, and/or
      education level. We also found that because the actual risk of infection varies
      across populations, activities such as direct macaque contact and pet ownership,
      could be putting individuals at real risk in certain contexts. Thus, we show that
      human demographics and social structure can influence willingness to participate
      in behaviors putting them at increased risk for exposure to parasites.

PMID- 24123084
TI  - Building partnerships to target sickle cell anemia in Africa.

PMID- 24123085
TI  - The distally based peroneus brevis muscle flap-clinical series and review of the
      literature.
AB  - The distally pedicled peroneus brevis muscle flap is rarely used for defect
      coverage in the distal lower leg. The purpose of this article was to present our
      clinical series and provide a review of the literature to analyze the overall
      complication rates and safety of this flap. In our clinical series of 10 patients
      undergoing reconstruction with the flap, one necrosis of the distal half of the
      flap and one necrosis of a skin graft occurred. Our review of the literature
      identified 192 patients undergoing reconstruction with distally pedicled peroneus
      brevis flaps. The overall complication rate was 41.6%. Typical indications,
      complications, advantages and disadvantages to alternatives are discussed. The
      distally pedicled peroneus brevis flap is an interesting option for soft tissue
      coverage in the distal lower leg. The donor site can always be closed primarily,
      the anatomy is constant and complication rates are comparable to alternatives in
      this region like the distally based sural fasciocutaneous flap.

PMID- 24123086
TI  - Effect of interfacial Maxwell stress on time periodic electro-osmotic flow in a
      thin liquid film with a flat interface.
AB  - Electro-osmotic flows (EOF) have seen remarkable applications in lab-on-a-chip
      based microdevices owing to their lack of moving components, durability, and
      nondispersive nature of the flow profiles under specifically designed conditions.
      However, such flows may typically suffer from classical Faradaic artifacts like
      electrolysis of the solvent, which affects the flow rate control. Such a problem
      has been seen to be overcome by employing time periodic EOFs. Electric field
      induced transport of a conductive liquid is another nontrivial problem that
      requires careful study of interfacial dynamics in response to such an oscillatory
      flow actuation. The present study highlights the role of electric field generated
      Maxwell stress and free surface potential along with the electric double layer
      thickness and forcing frequency, toward influencing the interfacial transport and
      fluid flow in free-surface electro-osmosis under a periodically varying external
      electric field, in a semi-analytical formalism. Our results reveal interesting
      regimes over which the pertinent interfacial phenomena as well as bulk transport
      characteristics may be favorably tuned by employing time varying electrical
      fields. 

PMID- 24123089
TI  - Bayesian adaptive determination of the sample size required to assure acceptably
      low adverse event risk.
AB  - An emerging concern with new therapeutic agents, especially treatments for type 2
      diabetes, a prevalent condition that increases an individual's risk of heart
      attack or stroke, is the likelihood of adverse events, especially cardiovascular
      events, that the new agents may cause. These concerns have led to regulatory
      requirements for demonstrating that a new agent increases the risk of an adverse
      event relative to a control by no more than, say, 30% or 80% with high (e.g.,
      97.5%) confidence. We describe a Bayesian adaptive procedure for determining if
      the sample size for a development program needs to be increased and, if
      necessary, by how much, to provide the required assurance of limited risk. The
      decision is based on the predictive likelihood of a sufficiently high posterior
      probability that the relative risk is no more than a specified bound. Allowance
      can be made for between-center as well as within-center variability to
      accommodate large-scale developmental programs, and design alternatives (e.g.,
      many small centers, few large centers) for obtaining additional data if needed
      can be explored. Binomial or Poisson likelihoods can be used, and center-level
      covariates can be accommodated. The predictive likelihoods are explored under
      various conditions to assess the statistical properties of the method.

PMID- 24123088
TI  - In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.
AB  - Although patients with type 2 diabetes (T2D) are at significant risk for well
      recognized diabetic complications, including macrovascular disease, retinopathy,
      nephropathy, and neuropathy, it is also clear that T2D patients are at increased
      risk for fragility fractures. Furthermore, fragility fractures in patients with
      T2D occur at higher bone mineral density (BMD) values compared to nondiabetic
      controls, suggesting abnormalities in bone material strength (BMS) and/or bone
      microarchitecture (bone "quality"). Thus, we performed in vivo microindentation
      testing of the tibia to directly measure BMS in 60 postmenopausal women (age
      range, 50-80 years) including 30 patients diagnosed with T2D for >10 years and 30
      age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray
      absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed
      from high-resolution peripheral quantitative computed tomography (HRpQCT) images
      of the distal radius and tibia. Compared to controls, T2D patients had
      significantly lower BMS: unadjusted (-11.7%; p<0.001); following adjustment for
      body mass index (BMI) (-10.5%; p<0.001); and following additional adjustment for
      age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (
      9.2%; p=0.022). By contrast, after adjustment for confounding by BMI, T2D
      patients had bone microarchitecture and BMD that were not significantly different
      than controls; however, radial cortical porosity tended to be higher in the T2D
      patients. In addition, patients with T2D had significantly reduced serum markers
      of bone turnover (all p<0.001) compared to controls. Of note, in patients with
      T2D, the average glycated hemoglobin level over the previous 10 years was
      negatively correlated with BMS (r=-0.41; p=0.026). In conclusion, these findings
      represent the first demonstration of compromised BMS in patients with T2D.
      Furthermore, our results confirm previous studies demonstrating low bone turnover
      in patients with T2D and highlight the potential detrimental effects of prolonged
      hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as
      another important target tissue subject to diabetic complications. (c) 2014
      American Society for Bone and Mineral Research.

PMID- 24123087
TI  - Dopamine overdose hypothesis: evidence and clinical implications.
AB  - About a half a century has passed since dopamine was identified as a
      neurotransmitter, and it has been several decades since it was established that
      people with Parkinson's disease receive motor symptom relief from oral levodopa.
      Despite the evidence that levodopa can reduce motor symptoms, there has been a
      developing body of literature that dopaminergic therapy can improve cognitive
      functions in some patients but make them worse in others. Over the past two
      decades, several laboratories have shown that dopaminergic medications can impair
      the action of intact neural structures and impair the behaviors associated with
      these structures. In this review, we consider the evidence that has accumulated
      in the areas of reversal learning, motor sequence learning, and other cognitive
      tasks. The purported inverted-U shaped relationship between dopamine levels and
      performance is complex and includes many contributory factors. The regional
      striatal topography of nigrostriatal denervation is a critical factor, as
      supported by multimodal neuroimaging studies. A patient's individual genotype
      will determine the relative baseline position on this inverted-U curve.
      Dopaminergic pharmacotherapy and individual gene polymorphisms can affect the
      mesolimbic and prefrontal cortical dopaminergic functions in a comparable,
      inverted-U dose-response relationship. Depending on these factors, a patient can
      respond positively or negatively to levodopa when performing reversal learning
      and motor sequence learning tasks. These tasks may continue to be relevant as our
      society moves to increased technological demands of a digital world that requires
      newly learned motor sequences and adaptive behaviors to manage daily life
      activities.

PMID- 24123090
TI  - Correlation between hepatitis B virus surface antigen level and alpha-fetoprotein
      in patients free of hepatocellular carcinoma or severe hepatitis.
AB  - Alfa-fetoprotein (AFP) is used as a marker of early hepatocarcinogenesis.
      However, the impact of hepatitis B virus surface antigen (HBsAg) on this
      relationship in patients with HBV infection is not clear. The present study
      evaluated the relation between HBsAg and AFP levels at the initial visit in 1,610
      untreated HBV patients, free of hepatocellular carcinoma (HCC) or severe
      hepatitis. The cumulative rate of HCC was significantly lower in patients with a
      low AFP level (<=10 ug/L; below the upper limit of normal) than in those with a
      high AFP level (>=11 ug/L) at the initial visit. In patients with HBsAg levels
      more than 500 IU/ml, HBsAg levels correlated significantly and negatively with
      AFP levels, and significantly with platelet count. Multivariate analysis of data
      of patients with HBsAg more than 500 IU/ml identified HBsAg (<7,000 IU/ml),
      albumin (<3.9 g/dl), platelet count (<20.0 * 10(4) /mm(3)), gamma-glutamyl
      transpeptidase (>=50 IU/L), aspartate aminotransferase (>=34 IU/L), HBeAg
      (positive), and HBV core-related antigen (>=3.0 log U/ml) as determinants of a
      high AFP. Especially, in patients with HBsAg more than 500 IU/ml and low
      transaminase levels (below the upper limit of normal), HBsAg was identified as
      significant determinant of a high AFP. On the other hand, in patients with HBsAg
      less than 500 IU/ml, multivariate analysis identified albumin, gamma-glutamyl
      transpeptidase, and HBV core-related antigen as determinants of a high AFP. The
      results indicated that HBsAg level seems to affect, at least in part, the AFP
      levels, and that it can be used as a surrogate marker of early
      hepatocarcinogenesis.

PMID- 24123091
TI  - Antitumor CD8+ T cells in hepatocellular carcinoma: present but exhausted.

PMID- 24123092
TI  - Multiple actions of Lucilia sericata larvae in hard-to-heal wounds: larval
      secretions contain molecules that accelerate wound healing, reduce chronic
      inflammation and inhibit bacterial infection.
AB  - In Europe ~15,000 patients receive larval therapy for wound treatment annually.
      Over the past few years, clinical studies have demonstrated the success of larvae
      of Lucilia sericata as debridement agents. This is based on a combination of
      physical and biochemical actions. Laboratory investigations have advanced our
      understanding of the biochemical mechanisms underlying the beneficial effects of
      larval secretions, including removal of dead tissue, reduction of the bacterial
      burden, and promotion of tissue regeneration. The present article summarizes our
      current understanding of the microbiological, immunological, and wound healing
      actions of larval therapy, and the molecules involved in these beneficial
      effects. Future studies will focus on the isolation, identification, and
      (pre)clinical testing of the effective molecules of L. sericata larvae. These
      molecules may be candidates for the development of new agents for the treatment
      of several infectious and inflammatory diseases, including chronic wounds. 

PMID- 24123093
TI  - High cortisol and cortisone levels are associated with breast milk dioxin
      concentrations in Vietnamese women.
AB  - OBJECTIVE: Dioxin (polychlorinated dibenzodioxins+polychlorinated dibenzofurans)
      is one of the most toxic chemical substances known. Although it is suspected to
      cause endocrine disruption, very few epidemiological studies have been carried
      out on its effects on human steroid hormones. The aim of this study was to
      elucidate the association of dioxin exposure with steroid hormone levels in the
      saliva and serum of Vietnamese women. STUDY DESIGN: Two areas, namely Phu Cat
      (hot spot) and Kim Bang (nonexposed area), were selected for the study. The study
      subjects consisted of 51 and 58 women respectively. Saliva, blood, and breast
      milk samples were collected from the subjects in both the areas. METHODS:
      Cortisol, cortisone, DHEA, androstenedione, estrone, and estradiol levels in
      serum and saliva were determined by liquid chromatography-tandem mass
      spectrometry; dioxin concentrations in breast milk were measured by gas
      chromatography-mass spectrometry. RESULTS: Dioxin concentrations in the breast
      milk of women from the dioxin hot spot were three to four times higher than those
      in the breast milk of women from the nonexposed area. Good correlations were
      found between the levels of six steroid hormones in saliva and those in serum
      respectively. Salivary and serum cortisol and cortisone levels in women from the
      dioxin hot spot were significantly higher than those in women from the nonexposed
      area (P<0.001) and those in all the subjects were positively associated with
      dioxin concentrations in Vietnamese women (P<0.01). CONCLUSION: These results
      suggest that dioxin influences steroidogenesis in humans. Saliva samples can be
      used for hormone analysis and are therefore excellent specimens in
      epidemiological studies.

PMID- 24123094
TI  - Low-dose hydrocortisone replacement therapy is associated with improved bone
      remodelling balance in hypopituitary male patients.
AB  - OBJECTIVE: Glucocorticoid (GC) therapy is associated with adverse effects on bone
      metabolism, yet the effects of different GC physiological replacement regimens in
      hypopituitarism are not well characterised. We aimed to assess the effect of
      three hydrocortisone (HC) replacement dose regimens on bone turnover. STUDY
      DESIGN: An open cross-over study randomising ten hypopituitary men with severe
      acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and
      10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg
      tarde). METHODS: Following 6 weeks of each regimen, the participants underwent 24
      h serum cortisol sampling and measurement of bone turnover markers: bone-specific
      alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin
      (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant
      acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an
      absolute ratio (PINP:CTX-I) and as an index using standardised scores derived
      from the matched controls. RESULTS: There were significant increases in the
      concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and
      in the PINP:CTX-I ratio (P=0.015), and a more positive bone remodelling balance
      index (P=0.03) was observed in patients on the lowest dose C than in those on the
      highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX
      I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and
      with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on
      dose C. In patients receiving the lower-dose regimen, trough cortisol
      concentrations correlated with increased bone formation and resorption.
      CONCLUSION: Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated
      with increased bone formation and a positive bone remodelling balance. This may
      have a long-term beneficial effect on bone health.

PMID- 24123095
TI  - Oral liquid levothyroxine treatment at breakfast: a mistake?
AB  - OBJECTIVE: Taking levothyroxine (L-T4) with coffee or with water followed by
      coffee intake within a few minutes results in poor TSH response in many patients.
      T4 is available in tablet form worldwide, but novel formulations in soft gel
      capsule or liquid form are now available. DESIGN: We fortuitously identified a
      euthyroid patient who wrongly consumed liquid L-T4 with coffee at breakfast;
      after changing the time of consumption to 30 min before breakfast, no change in
      TSH, free T4 (fT4), and free tri-iodothyronine (fT3) concentrations was observed.
      Once the first patient was identified, additional stable euthyroid patients who
      consumed liquid L-T4 with coffee were identified. METHODS: Patients were
      recruited by searching our 'thyroid patients' database. All the patients on
      liquid L-T4 treatment were contacted by phone to ask them whether they took L-T4
      at breakfast. We identified 54 patients who were submitted to TSH, fT4, and fT3
      evaluation, with the indication that the same dosage of L-T4 be consumed 30 min
      before breakfast. We determined their TSH, fT4, and fT3 concentrations after 3
      and 6 months again. RESULTS: no significant difference in thyroid hormone
      concentrations was observed in patients when they consumed L-T4 at breakfast or
      when they consumed it 30 min before breakfast for 3 and 6 months (TSH: 2.5+/-1.1
      vs 2.5+/-1.1 and 2.4+/-1.1 mIU/l respectively, fT4: 12.4+/-2.4 vs 12.5+/-2.4 and
      12.3+/-2.1 pg/ml respectively, and fT3: 3.4+/-0.6 vs 3.4+/-0.6 and 3.3+/-0.5
      pg/ml respectively). CONCLUSION: Oral liquid L-T4 formulations could diminish the
      problem of L-T4 malabsorption caused by coffee when using traditional tablet
      formulations.

PMID- 24123096
TI  - Restoration: potential for compensatory changes in numbers of neurons in adult
      human brain.

PMID- 24123097
TI  - On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular
      carcinoma in patients with chronic hepatitis B receiving entecavir.
AB  - Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular
      carcinoma (HCC) surveillance, which is criticized as neither sensitive nor
      specific in active hepatitis and liver cirrhosis. The aim of this study was to
      determine the performance of AFP as a tumor marker for HCC in entecavir-treated
      patients with chronic hepatitis B (CHB). This was a retrospective-prospective
      cohort study of 1,531 entecavir-treated patients under regular HCC surveillance
      with AFP and ultrasonography. Mean age was 52 +/- 12 years; 1,099 (72%) patients
      were male and 332 (21.7%) had clinical evidence of cirrhosis. At a mean follow-up
      of 51 +/- 13 months, 57 (2.9%) patients developed HCC (median size: 3.3 cm). AFP
      fluctuated with alanine aminotransferase (ALT) and peaked at the time of starting
      entecavir, then gradually decreased after. AFP started to increase 6 months
      before the diagnosis of HCC. The receiver operator characteristic curve (AUROC)
      of AFP was highest at the time of HCC diagnosis (0.85; 95% confidence interval
      [CI]: 0.73-0.98) and remained satisfactory at 3 (0.82; 95% CI: 0.73-0.91) and 6
      months (0.79; 95% CI: 0.69-0.89) before the diagnosis. Using the conventional AFP
      cut-off (20 MUg/L) at month 0, the sensitivity and specificity to diagnose HCC
      were 38.6% and 98.9%, respectively. Adopting the lower cut-off value (6 MUg/L) of
      AFP level at month 0, sensitivity was increased to 80.7%, whereas specificity was
      decreased to 80.4%. CONCLUSION: On-treatment AFP is a specific tumor marker for
      HCC in CHB patients receiving entecavir therapy. Adopting a lower cut-off value
      of AFP level at 6 MUg/L would significantly increase the sensitivity for HCC
      detection.

PMID- 24123098
TI  - Plaque regression and progenitor cell mobilization with intensive lipid
      elimination regimen (PREMIER) trial design.
AB  - Progression of lipid rich necrotic core elements of atherosclerotic vulnerable
      plaque (VP) or its rupture leads to a majority of cardiovascular events.
      Endothelial progenitor cells (EPC) contribute to vascular healing and play a
      crucial role in repair following ischemic injury primarily by endothelialization
      of VP and neovascularization of ischemic myocardium. We present the rationale and
      design of the Plaque Regression and Progenitor Cell Mobilization with Intensive
      Lipid Elimination Regimen or the PREMIER Trial, which is designed to address the
      question for the very first time whether a highly intensive low-density
      lipoprotein (LDL)-lowering therapy with LDL-apheresis could lead to a more rapid
      and detectable reduction in coronary atheroma volume, along with a robust
      mobilization of EPC compared to standard statin therapy, in patients selected for
      percutaneous coronary intervention for an acute coronary syndrome.

PMID- 24123099
TI  - Decreased quantity and quality of the periarticular and nonperiarticular bone in
      patients with rheumatoid arthritis: a cross-sectional HR-pQCT study.
AB  - Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is
      well established that RA leads to bone loss and increased fracture risk, current
      knowledge on the microstructural changes of bone in RA is still limited. The
      purpose of this study was to assess the microstructure of periarticular and
      nonperiarticular bone in female and male RA patients and compare it with
      respective healthy controls. We performed two high-resolution peripheral
      quantitative computed tomography (HR-pQCT; Xtreme-CT) scans, one of the distal
      radius and one of the ultradistal radius in 90 patients with RA (60 females, 30
      males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and
      body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone
      microstructure including trabecular bone volume fraction (BV/TV), trabecular
      number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and
      cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius,
      trabecular (p=0.005 and p<0.001) and cortical BMD (p<0.001 and p<0.001) were
      significantly decreased in male and female patients with RA, respectively. BV/TV
      was also decreased at both sites, based on lower Tb.N in female RA (p<0.001 for
      both sites) and lower Tb.Th (p=0.034 and p=0.005) in male RA patients compared
      with respective healthy controls. Cortical thinning (p=0.018 and p=0.002) but not
      Ct.Po (p=0.070 and p=0.275) was pronounced in male and female RA patients at the
      distal radius. Cortical perimeter was increased in male and female RA patients at
      both sites. Multiple regression models showed that bone geometry (cortical
      perimeter) is predominantly influenced by age of the RA patient, cortical
      thickness by both age and disease duration, and trabecular microstructure
      predominantly by the disease duration. In summary, these data show profound
      deterioration of bone microstructure in the appendicular skeleton of RA patients
      at both periarticular and nonperiarticular sites.

PMID- 24123100
TI  - BCL::Fold--protein topology determination from limited NMR restraints.
AB  - When experimental protein NMR data are too sparse to apply traditional structure
      determination techniques, de novo protein structure prediction methods can be
      leveraged. Here, we describe the incorporation of NMR restraints into the protein
      structure prediction algorithm BCL::Fold. The method assembles discreet secondary
      structure elements using a Monte Carlo sampling algorithm with a consensus
      knowledge-based energy function. New components were introduced into the energy
      function to accommodate chemical shift, nuclear Overhauser effect, and residual
      dipolar coupling data. In particular, since side chains are not explicitly
      modeled during the minimization process, a knowledge based potential was created
      to relate experimental side chain proton-proton distances to Cbeta -Cbeta
      distances. In a benchmark test of 67 proteins of known structure with the
      incorporation of sparse NMR restraints, the correct topology was sampled in 65
      cases, with an average best model RMSD100 of 3.4 +/- 1.3 A versus 6.0 +/- 2.0 A
      produced with the de novo method. Additionally, the correct topology is present
      in the best scoring 1% of models in 61 cases. The benchmark set includes both
      soluble and membrane proteins with up to 565 residues, indicating the method is
      robust and applicable to large and membrane proteins that are less likely to
      produce rich NMR datasets.

PMID- 24123101
TI  - Monitoring of threo-methylphenidate enantiomers in oral fluid by capillary
      electrophoresis with head-column field-amplified sample injection.
AB  - Threo-methylphenidate is a chiral psychostimulant drug widely prescribed to treat
      attention-deficit hyperactivity disorder in children and adolescents. An
      enantioselective CE-based assay with head-column field-amplified sample stacking
      for analysis of threo-methylphenidate enantiomers in liquid/liquid extracts of
      oral fluid is described. Analytes are electrokinetically injected across a short
      water plug placed at the capillary inlet and become stacked at the interface
      between plug and buffer. Enantiomeric separation occurs within a few minutes in a
      pH 3.0 phosphate/triethanolamine buffer containing 20 mg/mL (2-hydroxypropyl)
      beta-CD as chiral selector. The assay with six point multilevel internal
      calibration provides a linear response for each enantiomer in the 10-200 ng/mL
      concentration range, is simple, inexpensive, and reproducible, and has an LOQ of
      5 ng/mL. It was applied to oral fluid patient samples that were collected up to
      12 h after intake of an immediate release tablet and two different extended
      release formulations with racemic methylphenidate. Drug profiles could thereby be
      assessed in a stereoselective way. Almost no levorotary threo-methylphenidate
      enantiomer was detected after intake of the two extended release formulations,
      whereas this enantiomer was detected during the first 2.5 h after intake of the
      immediate release preparation. The noninvasive collection of oral fluid is an
      attractive alternative to plasma for the monitoring of methylphenidate exposure
      in the pediatric community.

PMID- 24123102
TI  - Compressed sensing of spatial electron paramagnetic resonance imaging.
AB  - PURPOSE: To improve image quality and reduce data requirements for spatial
      electron paramagnetic resonance imaging (EPRI) by developing a novel
      reconstruction approach using compressed sensing (CS). METHODS: EPRI is posed as
      an optimization problem, which is solved using regularized least-squares with
      sparsity promoting penalty terms, consisting of the l1 norms of the image itself
      and the total variation of the image. Pseudo-random sampling was employed to
      facilitate recovery of the sparse signal. The reconstruction was compared with
      the traditional filtered back-projection reconstruction for simulations,
      phantoms, isolated rat hearts, and mouse gastrointestinal (GI) tracts labeled
      with paramagnetic probes. RESULTS: A combination of pseudo-random sampling and CS
      was able to generate high-fidelity EPR images at high acceleration rates. For
      three-dimensional (3D) phantom imaging, CS-based EPRI showed little visual
      degradation at nine-fold acceleration. In rat heart datasets, CS-based EPRI
      produced high quality images with eight-fold acceleration. A high resolution
      mouse GI tract reconstruction demonstrated a visual improvement in spatial
      resolution and a doubling in signal-to-noise ratio (SNR). CONCLUSION: A novel 3D
      EPRI reconstruction using compressed sensing was developed and offers superior
      SNR and reduced artifacts from highly undersampled data.

PMID- 24123103
TI  - Monitoring of Calicivirus among day-care children: evidence of asymptomatic viral
      excretion and first report of GI.7 Norovirus and GI.3 Sapovirus in Brazil.
AB  - Caliciviruses (Norovirus and Sapovirus) are important causes of acute
      gastroenteritis, with Norovirus (NoV) considered the leading cause of epidemic
      non-bacterial acute gastroenteritis; however, molecular and epidemiological data
      of the circulating Calicivirus (CV) strains among day-care children are still
      considered scarce. The role of asymptomatic CV excretion on viral transmission
      also remains poorly understood. The aim of the present study was to monitor the
      occurrence of NoV and Sapovirus (SaV) in a day-care center and to describe the
      molecular epidemiology of the circulating strains. Genomic sequencing and
      phylogenetic analysis of the capsid region were carried out in CV positive
      samples obtained from children younger than 5 years, with or without diarrhea,
      between October 2009 and October 2011. A total of 539 fecal samples were screened
      for CV. Forty-three (8%) were positive for NoV and 25 (4.6%) for SaV.
      Surprisingly, positivity rates for CV were significant in asymptomatic children,
      and virus circulation was detected in every month of the study. Great genomic
      diversity of CV was observed, and the circulating NoV strains were: GII.6, GII.2,
      GII.1, GI.7, GII.4, and GI.1. The SaV genotypes GI.1 and GI.3 were also detected.
      Five CV outbreaks caused by distinct viral strains were documented. This study
      provides an insight on the genetic diversity of CV in a day-care in Central West
      Brazil, highlighting the probable role of asymptomatic viral excretion and the
      significance of semi-closed settings in the dissemination of these agents.

PMID- 24123104
TI  - Population-based meta-analysis of hydrochlorothiazide pharmacokinetics.
AB  - Hydrochlorothiazide (HCTZ) is a thiazide diuretic used for the treatment of
      hypertension and edema associated with fluid overload conditions such as
      congestive heart failure (CHF). A population-based meta-analysis approach in
      NONMEM(r) was used to develop a PK model to characterize the time-course of HCTZ
      concentrations in plasma and excretion into the urine for healthy subjects and
      CHF patients. Data from healthy subjects receiving 100 mg of oral HCTZ were
      supplemented with additional plasma concentration and urinary excretion versus
      time data published in the literature following administration of oral HCTZ doses
      ranging from 10 to 500 mg to healthy subjects or patients with renal failure, CHF
      or hypertension. A two-compartment model with first-order oral absorption, using
      a Weibull function, and first-order elimination best described HCTZ PK.
      Creatinine clearance (CLCR ) was a statistically significant predictor of renal
      clearance (CLR ). Non-renal clearance was estimated to be 2.44 l/h, CLR was 18.3
      l/h and T1/2,alpha was 1.6 h and T1/2,beta was 14.8 h for a typical individual
      with normal renal function (CLCR  = 120 ml/min). However, CLR was reduced to
      10.5, 5.47 and 2.70 l/h in mild (CLCR  = 80 ml/min), moderate (CLCR  = 50 ml/min)
      and severe (CLCR  = 30 ml/min) renal impairment, respectively. Model diagnostics
      helped to demonstrate that the population PK model reasonably predicts the rate
      of urinary HCTZ excretion over time using dosing history and estimated CLCR ,
      allowing for the convenient assessment of PK-PD relationships for HCTZ when given
      alone or in combination with other agents used to treat fluid overload
      conditions.

PMID- 24123105
TI  - Monitoring ovarian cycle activity via progestagens in urine and feces of female
      mountain gorillas: A comparison of EIA and LC-MS measurements.
AB  - Understanding the reproductive biology of endangered mountain gorillas (Gorilla
      beringei beringei) is essential for optimizing conservation strategies,
      determining any demographic impact of socioecological changes, and providing
      information for comparative studies of primates. Non-invasive techniques have
      been used to assess the reproductive function of many primates and the importance
      of validating the measurements of hormones metabolites is widely recognized
      because they may vary even within closely related species. To determine if it is
      possible to non-invasively monitor ovarian activity in wild mountain gorillas, we
      used enzyme immunoassays (EIA) to quantify both urinary and fecal excretion of
      immunoreactive pregnanediol-3-glucuronide (iPdG), defined as all metabolites
      detected by a pregnanediol-3-glucuronide immunoassay (PdG EIA). Simultaneously,
      we performed the liquid chromatography mass spectrometry (LC-MS) to quantify the
      excretion of pregnanediol in urine and feces. Samples were analyzed over nine
      cycles of five females from the habituated gorillas monitored by Karisoke
      Research Center, Rwanda. As an additional indicator for ovulation timing, estrone
      conjugates (E1C) were measured in a subset of urine samples. The concentrations
      of iPdG and pregnanediol measured in the same samples were significantly
      correlated. Urinary concentrations of iPdG and pregnanediol fluctuated over the
      menstrual cycle but did not reveal any cyclic pattern, whereas a typical
      preovulatory urinary E1C surge and postovulatory increases of fecal iPdG and
      pregnanediol were detected. The luteal peaks of iPdG and pregnanediol levels in
      feces were on average 2.8 and 7.6 times higher, respectively, than averaged
      levels in the corresponding follicular phase. The relative number of days with
      observed matings was higher within the presumed fertile window than in the
      preceding period. Overall, the results indicate that fecal analysis of iPdG and
      pregnanediol is suitable for detecting ovulation in female mountain gorillas.
      Urinary measurements using both EIA and LC-MS appeared to be uninformative for
      monitoring ovarian activity in this primate.

PMID- 24123106
TI  - ELF magnetic fields do not affect cell survival and DNA damage induced by
      ultraviolet B.
AB  - We investigated whether extremely low frequency (ELF) magnetic field exposure has
      modification effects on cell survival after ultraviolet B (UV-B) irradiation and
      on repair process of DNA damage induced by UV-B irradiation in WI38VA13 subcloned
      2RA and XP2OS(SV) cells. The ELF magnetic field exposure was conducted using a
      Helmholtz coil-based system that was designed to generate a sinusoidal magnetic
      field at 5 mT and 60 Hz. Cell survival was assessed by WST assay after UV-B
      irradiation at 20-80 J/m(2) , ELF magnetic field exposure for 24 h, followed by
      incubation for 48 h. DNA damage was assessed by quantification of cyclobutane
      pyrimidine dimer formation and 6-4 photoproduct formation using ELISA after UV-B
      irradiation at 20-80 J/m(2) followed by ELF magnetic field exposure for 24 h. No
      significant changes were observed in cell survival between ELF magnetic field and
      sham exposures. Similarly, DNA damage induced by UV-B irradiation did not change
      significantly following ELF magnetic field exposure. Our results suggest that ELF
      magnetic field exposure at 5 mT does not have modification effect on cell
      survival after UV-B irradiation and on repair process of DNA damage induced by UV
      B irradiation.

PMID- 24123108
TI  - Treatment of gastric marginal zone B-cell lymphoma of the mucosa-associated
      lymphoid tissue with rituximab, cyclophosphamide, vincristine and prednisone.
AB  - There is no standard treatment for patients with gastric marginal zone B-cell
      lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who are
      resistant to, or ineligible for, anti-Helicobacter pylori (anti-HP) therapy. In
      this study, we investigated the activity of the rituximab, cyclophosphamide,
      vincristine and prednisone (R-CVP) regimen in patients with gastric MALT
      lymphoma. Patients were included provided they had untreated gastric MALT
      lymphoma (except for anti-HP therapy) and were resistant to, or ineligible for,
      anti-HP therapy. Treatment plan consisted of six to eight 21-day cycles of the R
      CVP chemotherapy regimen. Toxicity, response, relapse and survival were
      evaluated. Twenty patients (12 women and 8 men) were included in the analyses
      with median age of 59 years. Thirteen patients (65%) had stage I tumours, and
      seven patients (35%) had stages II-IV tumours. The overall response rate was
      100%, with 19 (95%) complete responses and one (5%) partial response. Regimen
      toxicity was mild and mainly hematological, and no cases of gastric bleeding or
      perforation occurred. After a median follow-up of 56.3 months, three patients had
      relapsed, and 19 patients remained alive (specific lymphoma survival 100%), of
      whom 17 had no evidence of disease. In our experience, the R-CVP regimen is a
      well-tolerated and effective treatment for patients with gastric MALT lymphoma
      who are resistant to, or ineligible for, anti-HP therapy.

PMID- 24123109
TI  - Systemic mastocytosis - the importance of looking within bone marrow fragments:
      AJH Educational Material.

PMID- 24123110
TI  - Calcific periarthritis as the only clinical manifestation of hypophosphatasia in
      middle-aged sisters.
AB  - Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum
      alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within
      the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP,
      extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate
      and inhibitor of mineralization, leads frequently to premature tooth loss and
      often to rickets or osteomalacia. In affected adults, the excess PPi sometimes
      also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy,
      or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in
      ligaments or around joints when the condition is called calcific periarthritis
      (CP). We report three middle-aged sisters with CP as the only clinical
      manifestation of HPP. Each presented during early adult life with recurrent
      episodes of pain principally around the shoulders, elbows, wrists, hips, or
      Achilles tendon. Otherwise, they were in good health, including no history of
      unusual dental disease, fractures, or pseudofractures. Calcific deposits were
      identified in symptomatic areas principally by ultrasonographic assessment but
      also confirmed radiographically. All three sisters had low serum levels of total
      and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of
      the TNSALP substrate pyridoxal 5'-phosphate together characteristic of HPP.
      Mutation analysis revealed that each carried a single unique 18-bp duplication
      within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons
      and their mother, who was without signs of CPPD deposition or CP but had knee
      osteoarthritis. We find that CP can be the only complication of HPP in adults.
      Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a
      useful sign of HPP, especially when the CP is familial.

PMID- 24123111
TI  - Diagnostic accuracy of (18) F-methylcholine positron emission tomography/computed
      tomography for intra- and extrahepatic hepatocellular carcinoma.
AB  - Diagnosis of hepatocellular carcinoma (HCC) primarily involves imaging. The aim
      of this study was to assess the accuracy of (18) F-fluorocholine ((18) F-FCH)
      positron emission tomography (PET) for detection of HCC and evaluation of extent
      of disease. Patients with HCC >1 cm were included between 2009 and July 2011, and
      follow-up closed in February 2013. Diagnosis was based on American Association
      for the Study of Liver Diseases criteria, and all patients underwent (18) F-FCH
      PET/computed tomography (CT) at baseline before treatment, 6 underwent a second
      PET/CT posttreatment, and 1 a third during follow-up. Whole-body PET and low-dose
      CT imaging were performed 15 minutes after (18) F-FCH injection. Evaluation of
      imaging was done with standardized uptake value (SUV) ratios: SUV maximum of the
      lesion divided by the SUV mean of surrounding tissue. Statistical analyses
      included descriptive analyses, receiver operating characteristic curve, McNemar's
      test, and Kaplan-Meier's test at 5% level of significance. Twenty-nine patients
      revealed 53 intrahepatic lesions. In 48 of 53 lesions, (18) F-FCH PET was
      positive (SUVratio , 1.95 +/- 0.66; sensitivity, 88%; specificity, 100%). PET/CT
      showed uptake in 18 extrahepatic lesions and no uptake in 3 lesions affirmed non
      HCC lesions; all lesions were confirmed with additional investigation (accuracy,
      100%). In 17 of 29 patients, additional lesions were found on PET/CT imaging,
      with implications for treatment in 15 patients. Posttreatment PET/CT showed
      identical results, compared with standard treatment evaluation. CONCLUSION: This
      study shows additional value of (18) F-FCH PET/CT for patients with HCC. (18) F
      FCH PET/CT has implications for staging, management, and treatment evaluation
      because of accurate assessment of extrahepatic disease.

PMID- 24123112
TI  - Seasonal distribution of severe ADAMTS13 deficient idiopathic thrombotic
      thrombocytopenic purpura.
AB  - BACKGROUND: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare yet
      potentially fatal thrombotic microangiopathy. Severe deficiency of ADAMTS13
      activity via autoantibody formation has been associated with idiopathic TTP;
      however, specific triggers are poorly defined. Previous studies have reported
      seasonal associations of TTP, with warm-weather seasons appearing to have the
      strongest predilection. We characterized the seasonal distribution of severe
      ADAMTS13 deficient idiopathic TTP at our multi-hospital institution. METHODS:
      Apheresis records from 2005-2012 were queried for patients with a clinical
      diagnosis of TTP, accompanying pre-plasmapheresis ADAMTS13 activity <10%, and no
      other explanations for thrombotic microangiopathy. Date of admission and ADAMTS13
      activity were collected. Both initial episodes and relapses in patients whose
      initial episodes occurred since 2005 were included in the analysis. Goodness-of
      fit chi-square analysis was performed and statistical significance was defined as
      p<0.05. RESULTS: Of 237 consecutive new patients with a suspected clinical
      diagnosis of TTP, 73 patients met inclusion criteria and had a total of 110
      unique presentations for either initial TTP episodes or TTP relapses. Sixteen
      patients had 37 relapses of their idiopathic TTP (range 1-7). No statistically
      significant seasonal or monthly associations were identified with either initial
      or any TTP episodes. CONCLUSION: A seasonal association of severe ADAMTS13
      deficient idiopathic TTP was not observed. Unknown variables may explain previous
      observations of seasonal associations of idiopathic TTP in other regions of the
      United States. Thus, individual institutions should characterize their own
      seasonal distributions of idiopathic TTP as part of the exploration of possible
      disease triggers in their respective areas.

PMID- 24123113
TI  - Multiparametric optical and MR imaging demonstrate inhibition of tumor
      angiogenesis natural history by mural cell therapy.
AB  - PURPOSE: To determine whether functional imaging using MRI and fibered confocal
      fluorescence microscopy (FCFM) could be used to monitor cell therapy by mural
      progenitor cells (MPC). METHODS: Fifty mice bearing TC1 murine xenograft tumors
      were allocated into: control (n = 17), sham (phosphate buffer saline, n = 16),
      and MPC-treated (MPC, n = 17) groups. MRI was performed before (D0 ) and 7 days
      (D7 ) after injection measuring tumor size, R2 * under air, oxygen, and carbogen
      using blood oxygen level dependent (BOLD) and f (fraction linked to
      microcirculation), D* (perfusion related coefficient) and Dr (restricted
      diffusion coefficient) using diffusion-weighted sequences based on the IVIM
      (intravoxel incoherent motion) method. FCFM was performed at D7 measuring "index
      leakage" (capillary permeability). RESULTS: Tumor growth was significantly slowed
      down in the MPC-treated animals (P = 0.002) on D7 . R2 *air significantly
      decreased in controls between D0 and D7 (P = 0.03), reflecting a decrease in
      tumor oxygenation. DeltaR2 *O2CO2 significantly increased in controls between D0
      and D7 (P = 0.01) reflecting loss of vessel response to carbogen. D*
      significantly decreased in controls between D0 and D7 (P = 0.03). Finally, "index
      leakage" was lower in the MPC-treated tumors (P = 0,009). CONCLUSION: Treatment
      by MPC resulted in slowing down of tumor growth, capillary permeability decrease,
      and stabilization of tumor angiogenesis.

PMID- 24123114
TI  - Hepatitis C virus clearance correlates with HLA-DR expression on proliferating
      CD8+ T cells in immune-primed chimpanzees.
AB  - Vaccination of chimpanzees against hepatitis C virus (HCV) using T-cell-based
      vaccines targeting nonstructural proteins has not resulted in the same levels of
      control and clearance as those seen in animals reexposed after HCV clearance. We
      hypothesized that the outcome of infection depends on the different subtypes of
      activated T cells. We used multicolor flow cytometry to evaluate activation
      (CD38+/HLA-DR+) and proliferation (Ki67+/Bcl-2-low) profiles of CD4+ and CD8+ T
      cells in peripheral blood before and after challenge in chimpanzees vaccinated
      using DNA/adenovirus, mock-vaccinated, and chimpanzees that had spontaneously
      cleared infection (rechallenged). The frequencies of activated or proliferating
      CD8+ T cells peaked at 2 weeks postchallenge in the vaccinated and rechallenged
      animals, coinciding with reductions in viral titers. However, the magnitude of
      the responses did not correlate with outcome or sustained control of viral
      replication. In contrast, proliferation of the CD8+ T cells coexpressing HLA-DR
      either with or without CD38 expression was significantly higher at challenge in
      animals that rapidly cleared HCV and remained so throughout the follow-up period.
      CONCLUSION: Our data suggest that the appearance of proliferating HLA-DR+/CD8+ T
      cells can be used as a predictor of a successfully primed memory immune response
      against HCV and as a marker of effective vaccination in clinical trials.

PMID- 24123115
TI  - Evaluation of electroosmotic markers in aqueous and nonaqueous capillary
      electrophoresis.
AB  - The most common method to determine the EOF in CE is to measure the migration
      time for a neutral marker. In this study, 12 compounds (three novel and some
      previously used) were investigated as EOF markers in aqueous and nonaqueous BGEs.
      In the aqueous buffer systems (ammonium acetate, sodium phosphate, and sodium
      borate) the evaluation included a wide pH range (2-12). Two BGEs contained chiral
      selectors (sulphated-beta-CD, (-)-diketogulonic acid) and one that contained a
      micellar agent (SDS) were included in the study. The majority of the evaluated
      compounds were found to migrate with the EOF in the water-based BGEs and are thus
      useful as EOF markers. However, in the SDS-based BGE only four of the compounds
      (acetone, acrylamide, DMSO, and ethanol) were found to be applicable. In the
      nonaqueous BGEs 11 markers (acetone, acetophenone, acrylamide, anthracene,
      benzene, 4-(4-methoxybenzylamino)-7-nitro-2,1,3-benzoxadiazole, benzyl alcohol,
      2,5-diphenyloxazole, ethanol, flavone, and mesityl oxide) seemed to be functional
      as EOF markers. Even though several of the evaluated compounds can be used as EOF
      markers in the investigated BGEs, the authors would recommend the use of
      acrylamide as a general marker for UV detection. Furthermore, the four
      fluorescent markers (of which three were novel) gave RSD values equal to the
      other markers and can be used for the determination of the EOF in CE or microchip
      CE with fluorescence detection. 

PMID- 24123116
TI  - Clinical issues in the treatment of anxiety and depression in older adults with
      Parkinson's disease.
AB  - A significant proportion of persons affected by Parkinson's disease (PD) are over
      age 65 years. Mental health issues are often less a focus of treatment in this
      population than physical manifestations of the illness. Anxiety or depression
      alone, as well as comorbid depression and anxiety, are underrecognized in
      patients with PD and are associated with deleterious effects on physical and
      interpersonal functioning, negatively impacting quality of life and well-being.
      We offer a brief overview of salient clinical points with respect to assessment
      and treatment approaches to enhance efficacy of the treatment of mental health
      symptoms in older adults with PD. Cognitive behavior therapy involves the patient
      learning to overcome behavioral avoidance associated with anxiety and challenge
      unhelpful negative cognitions. It is suggested that cognitive behavior therapy is
      an effective approach to treatment of anxiety and depression in PD and should be
      offered as a treatment to patients.

PMID- 24123117
TI  - Distribution of JC virus genotypes among Serbian patients infected with HIV and
      in healthy donors.
AB  - Certain factors lead to increased reactivation of JC virus (JCV) and
      immunodeficiency seems to be the most important. JCV isolates can be classified
      into eight different genotypes and several subtypes based on nucleotide
      difference in the VP1 gene. JCV genotypes are strongly associated with particular
      ethnic groups and frequently used as genetic markers for human evolution and
      migration. The aim of this study was to determine the frequency of JCV urinary
      shedding and genotype distribution in Serbia among patients infected with HIV and
      healthy donors. Urine samples from 107 healthy donors and 93 patients infected
      with HIV were collected. PCR followed by sequence analysis was carried out using
      primers specific for VP1 and NCRR of the virus genome. Excretion rate of JCV-DNA
      in urine was higher in patients infected with HIV than in healthy donors (44.1%
      vs. 31.7%) although statistical significance was not found. Within the group
      infected with HIV, the degree of immunosuppression (measured by CD4(+) cell
      count) did not influence JCV excretion rate. Sequence analysis of JCV NCRR from
      both patients infected with HIV and healthy donors showed a pattern identical to
      archetype structure. In healthy Serbian donors the predominant genotype was 1
      (41.2%), followed by 4 (32.4%) and 2 (26.4%). On the other hand, genotype
      distribution pattern was different in patients infected with HIV: 2 (43.9%), 1
      (31.7%), and 4 (24.4%). This study showed that European, Eurasian, and Indian
      types are circulating in Serbia and that distribution corresponds to the origin
      of the inhabitants of Serbia.

PMID- 24123118
TI  - Nerve conduction studies in spastic paraplegia, optic atrophy, and neuropathy
      (SPOAN) syndrome.
AB  - INTRODUCTION: SPOAN (spastic paraplegia, optic atrophy, and neuropathy) syndrome
      is an autosomal recessive neurodegenerative disorder identified in a large
      consanguineous Brazilian family. METHODS: Twenty-seven patients with SPOAN
      syndrome (20 women), aged 4-58 years, underwent nerve conduction studies (NCS) of
      the median, ulnar, tibial, and fibular nerves, and sensory NCS of the median,
      ulnar, radial, sural, and superficial fibular nerves. RESULTS: Sensory nerve
      action potentials were absent in the lower limbs and absent in >80% of upper
      limbs. Motor NCS had reduced amplitudes and borderline velocities in the upper
      limbs and absent compound muscle action potentials (CMAPs) in the lower limbs.
      CONCLUSIONS: The neuropathy in SPOAN syndrome is a severe, early-onset sensory
      motor axonal polyneuropathy. Normal NCS seem to rule-out this condition.

PMID- 24123119
TI  - Precautions in using a perforator free flap to treat mandibuloacral dysplasia--a
      case report.
AB  - Mandibuloacral dysplasia (MAD) is a rare form of inherited lipodystrophy. The
      type B pattern is characterized by a generalized absence of subcutaneous tissues.
      There is also a deficiency of perivascular adiposity that makes the dissection
      not only of perforators and their source vessels difficult, but the recipient
      site vasculature as well. Perforator flaps in the MAD patient by definition will
      never be bulky, and instead a challenge in every respect as the perforators are
      extremely diminutive and therefore fragile. However, if a large, thin flap with a
      long pedicle of reasonable caliber is indicated, the attributes of a perforator
      flap may still be indicated as demonstrated in this case report for a
      recalcitrant heel pressure sore that had failed the usual conservative medical
      treatment.

PMID- 24123120
TI  - Spatially regularized estimation for the analysis of dynamic contrast-enhanced
      magnetic resonance imaging data.
AB  - Competing compartment models of different complexities have been used for the
      quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging
      data. We present a spatial elastic net approach that allows to estimate the
      number of compartments for each voxel such that the model complexity is not fixed
      a priori. A multi-compartment approach is considered, which is translated into a
      restricted least square model selection problem. This is done by using a set of
      basis functions for a given set of candidate rate constants. The form of the
      basis functions is derived from a kinetic model and thus describes the
      contribution of a specific compartment. Using a spatial elastic net estimator, we
      chose a sparse set of basis functions per voxel, and hence, rate constants of
      compartments. The spatial penalty takes into account the voxel structure of an
      image and performs better than a penalty treating voxels independently. The
      proposed estimation method is evaluated for simulated images and applied to an in
      vivo dataset.

PMID- 24123121
TI  - Thin layer chromatography-densitometric determination of some non-sedating
      antihistamines in combination with pseudoephedrine or acetaminophen in synthetic
      mixtures and in pharmaceutical formulations.
AB  - The combination of certain non-sedating antihistamines (NSA) such as fexofenadine
      (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or
      acetaminophen (ACE) is widely used in the treatment of allergic rhinitis,
      conjunctivitis and chronic urticaria. A rapid, simple, selective and precise
      densitometric method was developed and validated for simultaneous estimation of
      six synthetic binary mixtures and their pharmaceutical dosage forms. The method
      employed thin layer chromatography aluminum plates precoated with silica gel G 60
      F254 as the stationary phase. The mobile phases chosen for development gave
      compact bands for the mixtures FXD-PSE (I), KET-PSE (II), LOR-PSE (III), FXD-ACE
      (IV), KET-ACE (V) and LOR-ACE (VI) [Retardation factor (Rf ) values were (0.20,
      0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26),
      respectively]. Spectrodensitometric scanning integration was performed at 217,
      218, 218, 233, 272 and 251 nm for the mixtures I-VI, respectively. The linear
      regression data for the calibration plots showed an excellent linear
      relationship. The method was validated for precision, accuracy, robustness and
      recovery. Limits of detection and quantitation were calculated. Statistical
      analysis proved that the method is reproducible and selective for the
      simultaneous estimation of these binary mixtures.

PMID- 24123122
TI  - Vocal acoustics in the endangered proboscis monkey (Nasalis larvatus).
AB  - The endangered proboscis monkey (Nasalis larvatus) is a sexually highly dimorphic
      Old World primate endemic to the island of Borneo. Previous studies focused
      mainly on its ecology and behavior, but knowledge of its vocalizations is
      limited. The present study provides quantified information on vocal rate and on
      the vocal acoustics of the prominent calls of this species. We audio-recorded
      vocal behavior of 10 groups over two 4-month periods at the Lower Kinabatangan
      Wildlife Sanctuary in Sabah, Borneo. We observed monkeys and recorded calls in
      evening and morning sessions at sleeping trees along riverbanks. We found no
      differences in the vocal rate between evening and morning observation sessions.
      Based on multiparametric analysis, we identified acoustic features of the four
      common call-types "shrieks," "honks," "roars," and "brays." "Chorus" events were
      also noted in which multiple callers produced a mix of vocalizations. The four
      call-types were distinguishable based on a combination of fundamental frequency
      variation, call duration, and degree of voicing. Three of the call-types can be
      considered as "loud calls" and are therefore deemed promising candidates for non
      invasive, vocalization-based monitoring of proboscis monkeys for conservation
      purposes.

PMID- 24123123
TI  - Systems-based understanding of pharmacological responses with combinations of
      multidisciplinary methodologies.
AB  - The importance of systems-based pharmacological approaches to drug discovery and
      development has increasingly been recognized. This reviews summarizes recent
      advances in the development of systems pharmacology and introduces the methods
      used for analysis. To understand the cellular response at the molecular level,
      pathway maps must be prepared to show how the function of the constituent
      molecules within cells are linked and integrated to form molecular networks.
      First, the methods used to prepare these pathway maps, such as databases,
      knowledge bases and software platforms, are introduced. Then the mathematical
      theories used to analyse the behavior of molecular networks are summarized. To
      quantitatively predict cellular responses, simulations are performed that are
      based on the rate equations for each reaction within the pathway map. If the
      number of reactions described in the pathway map is small, and if the parameter
      values for the rate constants are available, it is possible accurately to
      simulate the behavior of the molecular networks. However, to analyse complex
      maps, mathematical abstraction is required. Such abstraction methods are
      important to integrate cellular responses and to understand tissue/organ and in
      vivo pharmacological/toxicological responses. The scope and limitations of the
      methods are also discussed.

PMID- 24123124
TI  - Secondary sugar binding site identified for LecA lectin from Pseudomonas
      aeruginosa.
AB  - The galactose-specific lectin LecA from Pseudomonas aeruginosa is a target for
      the development of new anti-infectious compounds. Sugar based molecules with anti
      adhesive properties present great potential in the fight against bacterial
      infection and biofilm formation. LecA is specific for oligosaccharides with
      terminal alpha-galactoside residues and displays strong affinity for melibiose
      (alphaGal1-6Glc) with a Kd of 38.8 uM. The crystal structure of LecA/melibiose
      complex shows classical calcium-bridged binding of alphaGal in the primary
      binding site but also revealed a secondary sugar binding site with glucose bound.
      This sugar binding site is in close proximity to the galactose binding one, is
      independent of calcium and mainly involves interactions with a symmetry-related
      protein. This discovery would help to the design of new potent inhibitors
      targeting both binding sites.

PMID- 24123125
TI  - The role and therapeutic potential of autophagy modulation in controlling virus
      induced cell death.
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved
      catabolic process in which the cytoplasmic content is sequestered and degraded by
      the lysosomal machinery in order to maintain cellular homeostasis or provide
      energy during metabolic and hypoxic stress. It also represents an important
      component of the host response against infectious agents, performing surveillance
      and effector functions involved in detection and clearance of pathogens,
      including viruses. Moreover, it appears that autophagy plays a major role in
      determining the fate of both virally infected and uninfected cells by blocking or
      promoting their death in a virus- and cell-type-dependent manner. We here review
      the current knowledge on the complex involvement of autophagy in survival and
      death of the host cells during viral infection, focusing on the molecular
      mechanisms underlying viral modulation of autophagic response and its
      interference with the cell death pathways. We also discuss a possible
      significance of the autophagy-dependent modulation of cell death for the outcome
      and therapy of viral infections, emphasizing the need for a time- and cell-type
      dependent fine-tuning of the autophagic response in achieving an optimal balance
      between beneficial and adverse effects.

PMID- 24123126
TI  - Marginal analysis of longitudinal ordinal data with misclassification in both
      response and covariates.
AB  - Marginal methods have been widely used for the analysis of longitudinal ordinal
      and categorical data. These models do not require full parametric assumptions on
      the joint distribution of repeated response measurements but only specify the
      marginal or even association structures. However, inference results obtained from
      these methods often incur serious bias when variables are subject to error. In
      this paper, we tackle the problem that misclassification exists in both response
      and categorical covariate variables. We develop a marginal method for
      misclassification adjustment, which utilizes second-order estimating functions
      and a functional modeling approach, and can yield consistent estimates and valid
      inference for mean and association parameters. We propose a two-stage estimation
      approach for cases in which validation data are available. Our simulation studies
      show good performance of the proposed method under a variety of settings.
      Although the proposed method is phrased to data with a longitudinal design, it
      also applies to correlated data arising from clustered and family studies, in
      which association parameters may be of scientific interest. The proposed method
      is applied to analyze a dataset from the Framingham Heart Study as an
      illustration. 

PMID- 24123127
TI  - Malaria and soil-transmitted intestinal helminth co-infection and its effect on
      anemia: a meta-analysis.
AB  - This study aimed to synthesize available evidence on the extent of malaria and
      soil-transmitted intestinal helminth (STH) co-infections in people living in
      endemic countries and to explore the effect of interactions between malaria and
      STHs on anemia. We searched relevant studies in electronic databases up to March
      2013. Studies comparing malaria and STH co-infected patients with those not co
      infected were included and the effect estimates were pooled using a random
      effects model. We identified 30 studies for meta-analyses of which 17 were cross
      sectional design. The majority of included studies (80%) were carried out in
      African countries. Among pregnant women, those infected with hookworm were found
      to have higher association with malaria infection compared with those without
      (summary OR: 1.36; 95% CI: 1.17-1.59; I(2): 0%). Among non-pregnant adults, the
      summary OR of the association between anemia and the combined malaria and STH was
      2.91 (1.38-6.14). The summary OR of the association between anemia and malaria
      alone was 1.53 (0.97-2.42), while the association between anemia and STH alone
      was 0.28 (0.04-1.95). There is no good evidence to support a different effect of
      malaria and STH on anemia. A subgroup analysis showed a higher risk of malaria
      infection in the primigravidae (summary OR: 1.61; 95% CI: 1.3-1.99; I(2): 0%). In
      conclusion, the malaria-STH co-infection was variable with complex outcomes on
      anemia. 

PMID- 24123129
TI  - Characterization of spermatogonial markers in the mature testis of the dogfish
      (Scyliorhinus canicula L.).
AB  - In dogfish, spermatogenesis progresses from a restricted germinative zone, which
      lines the dorsal testicular vessel. Single spermatogonia (A(s)), including the
      spermatogonial stem cells (SSCs), produce successively paired (A(p)),
      undifferentiated (A(u4) to A(u512)), and differentiated (A(d1) to A(d8))
      spermatogonia and preleptotene (PL) spermatocytes through 13 mitoses. Dogfish
      spermatogonial subpopulations present classical morphological characteristics but
      cannot be distinguished on the basis of molecular markers. This characterization
      has been initiated in mammals despite the difficulty to separate each
      spermatogonial subpopulation. For instance, both glial cell-derived neurotrophic
      factor family receptor alpha 1 (GFRalpha1) and promyelocytic leukemia zinc finger
      protein (PLZF) are markers of undifferentiated spermatogonia, whereas receptor
      tyrosine kinase C-kit is a marker of differentiated spermatogonia. The aim of
      this study is to characterize spermatogonial markers and to differentiate several
      spermatogonial subpopulations. Dogfish cDNA sequences have been identified and
      validated by phylogenetic analyses for gfralpha1, plzf, pou2, as well as for high
      mobility group box proteins 2 and 3 (hmgb2 and 3) and for mini-chromosome
      maintenance protein 6 (mcm6). We have used the anatomical advantage of the
      polarized dogfish testis to analyze the expression of those markers by RT-PCR and
      in situ hybridization. gfralpha1, pou2, and plzf have been detected in the
      testicular germinative zone, suggesting that spermatogonial markers are
      relatively well conserved among vertebrates but with a less restricted expression
      for plzf. Moreover, hmgb3 and mcm6 have been identified as new markers of
      differentiated spermatogonia. Finally, this first molecular characterization of
      spermatogonial subpopulations in a chondrichthyan model will be useful for
      further studies on the SSC niche evolution.

PMID- 24123128
TI  - Parent education and biologic factors influence on cognition in sickle cell
      anemia.
AB  - Children with sickle cell anemia have a high prevalence of silent cerebral
      infarcts (SCIs) that are associated with decreased full-scale intelligence
      quotient (FSIQ). While the educational attainment of parents is a known strong
      predictor of the cognitive development of children in general, the role of
      parental education in sickle cell anemia along with other factors that adversely
      affect cognitive function (anemia, cerebral infarcts) is not known. We tested the
      hypothesis that both the presence of SCI and parental education would impact FSIQ
      in children with sickle cell anemia. A multicenter, cross-sectional study was
      conducted in 19 US sites of the Silent Infarct Transfusion Trial among children
      with sickle cell anemia, age 5-15 years. All were screened for SCIs. Participants
      with and without SCI were administered the Wechsler Abbreviated Scale of
      Intelligence. A total of 150 participants (107 with and 43 without SCIs) were
      included in the analysis. In a multivariable linear regression model for FSIQ,
      the absence of college education for the head of household was associated with a
      decrease of 6.2 points (P = 0.005); presence of SCI with a 5.2 point decrease (P
      = 0.017); each $1000 of family income per capita with a 0.33 point increase (P =
      0.023); each increase of 1 year in age with a 0.96 point decrease (P = 0.023);
      and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point
      decrease (P = 0.030). In conclusion, FSIQ in children with sickle cell anemia is
      best accounted for by a multivariate model that includes both biologic and
      socioenvironmental factors.

PMID- 24123130
TI  - Paf receptor expression in the marsupial embryo and endometrium during embryonic
      diapause.
AB  - The control of reactivation from embryonic diapause in the tammar wallaby
      (Macropus eugenii) involves sequential activation of the corpus luteum, secretion
      of progesterone that stimulates endometrial secretion and subsequent changes in
      the uterine environment that activate the embryo. However, the precise signals
      between the endometrium and the blastocyst are currently unknown. In eutherians,
      both the phospholipid Paf and its receptor, platelet-activating factor receptor
      (PTAFR), are present in the embryo and the endometrium. In the tammar,
      endometrial Paf release in vitro increases around the time of the early
      progesterone pulse that occurs around the time of reactivation, but whether Paf
      can reactivate the blastocyst is unknown. We cloned and characterised the
      expression of PTAFR in the tammar embryo and endometrium at entry into embryonic
      diapause, during its maintenance and after reactivation. Tammar PTAFR sequence
      and protein were highly conserved with mammalian orthologues. In the endometrium,
      PTAFR was expressed at a constant level in the glandular epithelium across all
      stages and in the luminal epithelium during both diapause and reactivation. Thus,
      the presence of the receptor appears not to be a limiting factor for Paf actions
      in the endometrium. However, the low levels of PTAFR in the embryo during
      diapause, together with its up-regulation and subsequent internalisation at
      reactivation, supports earlier results suggesting that endometrial Paf could be
      involved in reactivation of the tammar blastocyst from embryonic diapause. 

PMID- 24123131
TI  - Long exposure to mature ooplasm can alter DNA methylation at imprinted loci in
      non-growing oocytes but not in prospermatogonia.
AB  - DNA methylation imprints that are established in spermatogenesis and oogenesis
      are essential for functional gametes. However, the mechanisms underlying gamete
      specific imprinting remain unclear. In this study, we investigated whether male
      and female gametes derived from newborn mice are epigenetically plastic and
      whether DNA methylation imprints are influenced by the niche surrounding the
      nuclei of the gametes. When prospermatogonia possessing sperm-specific DNA
      methylation imprints were fused with enucleated fully grown oocytes and exposed
      to the ooplasm for 5-6 days, the DNA methylation status of the reconstituted
      oocytes remained identical to that of prospermatogonia for all the imprinted
      regions analysed. These results suggest that the imprinting status of
      prospermatogonia is stable and that the epigenome of prospermatogonia loses
      sexual plasticity. By contrast, when non-growing oocytes lacking oocyte-specific
      DNA methylation imprints were fused with enucleated fully grown oocytes and the
      reconstituted oocytes were then cultured for 5-6 days, the Igf2r, Kcnq1ot1 and,
      unexpectedly, H19/Igf2 differentially methylated regions (DMRs) were methylated.
      Methylation imprints were entirely absent in oocytes derived from 5-day-old mice,
      and H19/Igf2 DMR is usually methylated only in spermatogenesis. These findings
      indicate that in the nuclei of non-growing oocytes the chromatin conformation
      changes and becomes permissive to DNA methyltransferases in some DMRs and that
      mechanisms for maintaining non-methylated status at the H19/Igf2 DMR are lost
      upon long exposure to mature ooplasm. 

PMID- 24123132
TI  - Another myc in the wall: microRNA-101 controls important functions in liver
      cancer formation.

PMID- 24123134
TI  - Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in
      adolescents: results from a randomized controlled trial.
AB  - Several organizations issued recommendations on desirable serum 25-hydroxy
      vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials
      allowing the formulation of evidence-based recommendations in adolescents are
      scarce. We investigated the ability of two doses of vitamin D3 in achieving
      recommended vitamin D levels in this age group. Post hoc analyses on data from a
      1-year double-blind trial that randomized 336 Lebanese adolescents, aged 13 +/- 2
      years, to placebo, vitamin D3 at 200 IU/day (low dose), or 2000 IU/day (high
      dose). Serum 25(OH)D level and proportions of children achieving levels >= 20
      ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 +/- 7 ng/mL,
      16.4 +/- 7 ng/mL in boys, and 14 +/- 8 ng/mL in girls, p=0.003, with a level >=
      20 ng/mL in 18% and >= 30 ng/mL in 5% of subjects. At 1 year, mean levels were
      18.6 +/- 6.6 ng/mL in the low-dose group, 17.1 +/- 6 ng/mL in girls, and 20.2 +/-
      7 ng/mL in boys, p=0.01, and 36.3 +/- 22.3 ng/mL in the high-dose group, with no
      sex differences. 25(OH)D increased to >= 20 ng/mL in 34% of children in the low
      dose and 96% in the high-dose group, being higher in boys in the low-dose arm
      only; it remained >= 30 ng/mL in 4% of children in the low-dose arm but increased
      to 64% in the high-dose arm. Baseline 25(OH)D level, body mass index (BMI), and
      vitamin D dose assigned were the most significant predictors for reaching a
      25(OH)D level >= 20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D
      level >= 20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose
      response studies are needed to determine in a definitive manner the daily
      allowance of vitamin D for Middle Eastern adolescents with a similar profile.

PMID- 24123136
TI  - Impaired force control in writer's cramp showing a bilateral deficit in
      sensorimotor integration.
AB  - BACKGROUND: Abnormal cortical processing of sensory inputs has been found
      bilaterally in writer's cramp (WC). This study tested the hypothesis that
      patients with WC have an impaired ability to adjust grip forces according to
      visual and somatosensory cues in both hands. METHODS: A unimanual visuomotor
      force-tracking task and a bimanual sense of effort force-matching task were
      performed by WC patients and healthy controls. RESULTS: In visuomotor tracking,
      WC patients showed increased error, greater variability, and longer release
      duration than controls. In the force-matching task, patients underestimated,
      whereas controls overestimated, the force applied in the other hand. Visuomotor
      tracking and force matching were equally impaired in both the symptomatic and
      nonsymptomatic hand in WC patients. CONCLUSIONS: This study provides evidence of
      bilaterally impaired grip-force control in WC, when using visual or sense of
      effort cues. This suggests a generalized subclinical deficit in sensorimotor
      integration in WC.

PMID- 24123135
TI  - Spiral tissue phase velocity mapping in a breath-hold with non-cartesian SENSE.
AB  - PURPOSE: Tissue phase velocity mapping (TPVM) is capable of reproducibly
      measuring regional myocardial velocities. However acquisition durations of
      navigator gated techniques are long and unpredictable while current breath-hold
      techniques have low temporal resolution. This study presents a spiral TPVM
      technique which acquires high resolution data within a clinically acceptable
      breath-hold duration. METHODS: Ten healthy volunteers are scanned using a spiral
      sequence with temporal resolution of 24 ms and spatial resolution of 1.7 * 1.7
      mm. Retrospective cardiac gating is used to acquire data over the entire cardiac
      cycle. The acquisition is accelerated by factors of 2 and 3 by use of non
      Cartesian SENSE implemented on the Gadgetron GPU system resulting in breath-holds
      of 17 and 13 heartbeats, respectively. Systolic, early diastolic, and atrial
      systolic global and regional longitudinal, circumferential, and radial velocities
      are determined. RESULTS: Global and regional velocities agree well with those
      previously reported. The two acceleration factors show no significant differences
      for any quantitative parameter and the results also closely match previously
      acquired higher spatial resolution navigator-gated data in the same subjects.
      CONCLUSION: By using spiral trajectories and non-Cartesian SENSE high resolution,
      TPVM data can be acquired within a clinically acceptable breath-hold.

PMID- 24123137
TI  - Comparison of the flap survival with ischemic preconditioning on different
      pedicles under varied ischemic intervals in a rat bilateral pedicled flap model.
AB  - The study was undertaken to search whether pedicle selection for ischemic
      preconditioning (IP) and duration of global ischemia applied after IP influenced
      efficacy of IP on flap viability in epigastric adipocutaneous island flap with
      bilateral pedicles in rat model. In total, 159 rats were divided into one control
      and three (primary, secondary, or bilateral pedicle) IP treatment groups. IP was
      performed on different pedicles by three cycles of 10 minutes of pedicle clamping
      and 10 minutes of release. After IP procedure secondary pedicle was ligated in
      all groups, and flaps were exposed to 0, 1, 2, 4, or 6 hours of global ischemia
      by clamping primary pedicle. In control groups, after the perfusion of bipedicled
      flaps for 1 hour, left pedicle was ligated and flaps were exposed to global
      ischemia as in IP groups. On day 5 post-surgery, tissue samples and topographic
      measurements were taken. No significant differences in semi-quantitative scorings
      of polymorphonuclear leukocytes infiltration, chronic inflammation, interstitial
      edema, neovascularization, VEGF, and CD105 expression levels among groups were
      found (P > 0.05). Percentages of necrosis were consistently smaller in IP groups
      compared to controls for the same duration of global ischemia, with exception of
      the no-ischemia. Area of necrosis was significantly smaller in primary IP group
      versus secondary IP group in the absence of global ischemia (P < 0.01). In the
      presence of global ischemia, both primary and secondary pedicle IP groups had
      significantly smaller percentage of necrosis than controls (P < 0.05) and there
      was no significant difference between primary and secondary IP groups (P > 0.05).
      Thus, IP performed on different pedicles may ameliorate flap survival in a
      comparable fashion, depending on the duration of global ischemia. Secondary
      pedicle IP was as effective as primary pedicle IP and may be feasible in free
      flap transfers.

PMID- 24123138
TI  - Flexible non-randomized response models for survey with sensitive question.
AB  - Non-randomized response (NRR) models have recently been developed for analyzing
      sensitive questions. Unlike traditional randomized response models, NRR models do
      not require a randomizing device, which limits the survey format and
      reproductivity of results. On the other hand, NRR models introduce a non
      sensitive question with binary outcomes in the questionnaire in order to protect
      privacy and encourage cooperation from respondents. Unfortunately, the proportion
      of subjects who possess the non-sensitive characteristic is assumed to be known,
      and the non-sensitive and sensitive questions are assumed to be independent. In
      this manuscript, we propose three new NRR models, which relax the aforementioned
      assumptions. Parameter and confidence interval estimates for the sensitive
      proportion will be developed. Optimal sample size allocations will be
      investigated. Performance of the proposed NRR models will be studied. A real
      survey on premarital sexual activity among college/university students in China
      is conducted to illustrate the proposed methodologies.

PMID- 24123139
TI  - Activity rating scales in adult muscle disease: how well do they actually
      measure?
AB  - INTRODUCTION: In an accompanying study we reported on the content of several
      activity rating scales that have been used for muscle disease. To further aid in
      achieving consensus we conducted a systematic review to assess the quality of the
      19 activity rating scales designed specifically for muscle disease. METHODS: We
      analyzed the measurement properties and the feasibility of the 19 instruments.
      Several databases were searched for studies relating to the quality of the
      instruments under review. Two independent reviewers selected studies and assessed
      instrument quality using pre-agreed criteria based on published frameworks.
      RESULTS: We found that none of the 19 instruments have sufficiently comprehensive
      reporting of measurement or feasibility performance as would be required by
      regulatory authorities. CONCLUSIONS: Further work is required urgently to address
      these deficiencies of reporting or acquiring additional data. Until then, there
      will remain a major barrier for translational research to overcome.

PMID- 24123140
TI  - Performance of ZDOCK in CAPRI rounds 20-26.
AB  - We report the performance of our approaches for protein-protein docking and
      interface analysis in CAPRI rounds 20-26. At the core of our pipeline was the
      ZDOCK program for rigid-body protein-protein docking. We then reranked the ZDOCK
      predictions using the ZRANK or IRAD scoring functions, pruned and analyzed energy
      landscapes using clustering, and analyzed the docking results using our interface
      prediction approach RCF. When possible, we used biological information from the
      literature to apply constraints to the search space during or after the ZDOCK
      runs. For approximately half of the standard docking challenges we made at least
      one prediction that was acceptable or better. For the scoring challenges we made
      acceptable or better predictions for all but one target. This indicates that our
      scoring functions are generally able to select the correct binding mode. 

PMID- 24123141
TI  - Applications of capillary electrophoresis in characterizing recombinant protein
      therapeutics.
AB  - The use of recombinant protein for therapeutic applications has increased
      significantly in the last three decades. The heterogeneity of these proteins,
      often caused by the complex biosynthesis pathways and the subsequent PTMs, poses
      a challenge for drug characterization to ensure its safety, quality, integrity,
      and efficacy. CE, with its simple instrumentation, superior separation
      efficiency, small sample consumption, and short analysis time, is a well-suited
      analytical tool for therapeutic protein characterization. Different separation
      modes, including CIEF, SDS-CGE, CZE, and CE-MS, provide complementary information
      of the proteins. The CE applications for recombinant therapeutic proteins from
      the year 2000 to June 2013 are reviewed and technical concerns are discussed in
      this article.

PMID- 24123142
TI  - Genetic analysis of poliovirus strains isolated from sewage in Poland.
AB  - The study describes genetic characterization of poliovirus (PV) strains isolated
      from sewage samples in Poland. The analyses were performed for the detection of
      any putative polio revertants and recombinants in three genomic regions by
      sequencing analysis. Thirty-six strains were analyzed. The analyzed strains were
      identified by neutralization assay as 7 strains of serotype P1, 10 strains of
      serotype P2, and 19 strains of serotype P3. Sewage isolates were sequenced in
      5'UTR, VP1, and 3D genomic regions. All detected PVs were classified as vaccine
      strains on the basis of VP1 sequence. Mutational differences in the VP1 sequences
      of isolated viruses ranged from 0.0% to 0.4%, indicating a limited replication
      period. The genetic analysis of the 3D region showed that some strains have
      recombinant genomes. Nine strains were found as dipartite recombinants (seven
      strains--S3/S2, one strain--S2/S1, one strain--S3/S1), while one strain was found
      as tripartite recombinant (S3/S2/S1). No recombinants with non-PV enteroviruses
      were identified. None of wild-type PVs or vaccine-derived polioviruses (VDPVs)
      were detected. This study showed the absence of wild or VDPV circulation in the
      country and demonstrated the usefulness of environmental surveillance in addition
      to acute flaccid paralysis (AFP) surveillance in support of polio eradication
      initiatives.

PMID- 24123143
TI  - Infection of common marmosets with hepatitis C virus/GB virus-B chimeras.
AB  - The development of vaccination and novel therapy for hepatitis C virus (HCV) has
      been hampered by the lack of suitable small-animal models. GB virus B (GBV-B),
      closely related to HCV, causes viral hepatitis in common marmosets (Callithrix
      jacchue jacchus) and might represent an attractive surrogate model for HCV
      infection. However, differences exist between GBV-B and HCV in spite of a short
      genetic distance between the two viruses. Here we report common marmosets
      infected with two HCV/GBV-B chimeras containing HCV structural genes coding for
      either whole core and envelope proteins (CE1E2p7) or full envelope proteins
      (E1E2p7) substituted for the counterpart elements of GBV-B. Naive animals
      intrahepatically injected with chimeric RNA transcripts or intravenously injected
      with sera from primary infected animals produced high levels of circulating
      infectious chimeric viruses and they developed chronic infection. Tacrolimus
      treated marmosets inoculated with a CE1E2p7 chimera had higher viral loads and
      long-term persistent infection. A moderate elevation of serum aspartate
      aminotransferase (AST) levels was observed in parallel with viral replication.
      Chimeras recovered from liver samples revealed 1/958 adaptive viral mutations.
      Histopathological changes typical of viral hepatitis were observed in liver
      tissues from all types of HCV chimeras-infected marmosets. HCV core and E2
      proteins were detected in liver tissues from infected animals by
      immunohistochemical staining. Fluctuations of chimeric virus replication in
      marmosets with spontaneous and sporadic viral clearance might be related to
      specific antibody and T-cell response to HCV proteins in vivo. Replication of
      CE1E2p7 chimera was observed in primary hepatocyte cultures by immunofluorescent
      staining in vitro. CONCLUSION: Infectious HCV chimeras causing chronic hepatitis
      in marmosets might constitute a small primate model suitable for evaluation of
      virus-cell interaction, vaccination, and antiviral therapy against HCV infection.

PMID- 24123144
TI  - The anticancer properties of Salvia miltiorrhiza Bunge (Danshen): a systematic
      review.
AB  - Salvia miltiorrhiza Bunge (Danshen in Chinese) is a classical Huoxue Huayu (a
      traditional Chinese medical term means promoting blood circulation and removing
      blood stasis) herb with 1000 years of clinical application. It mainly contains
      two groups of ingredients: the hydrophilic phenolic acids and the lipophilic
      tanshinones. Both groups have demonstrated multiple bioactivities, such as
      antioxidative stress, antiplatelet aggregation, anti-inflammation, among others.
      Recent data have demonstrated that its lipophilic compounds, especially the
      tanshinones, show potent anticancer activities both in vitro and in vivo. The
      anticancer effects of the hydrophilic phenolic acids have also been reported.
      Furthermore, tanshinones provide structural skeletons for chemical modifications,
      allowing for a series of derivatives of interests. This review provides a
      systematic summary of the anticancer profile and the underlying mechanisms of the
      bioactive compounds isolated from Danshen with special emphasis on tanshinones,
      aiming to bring new insights for further research and development of this ancient
      herb.

PMID- 24123145
TI  - Outlier robust model-assisted small area estimation.
AB  - Small area estimation with M-quantile models was proposed by Chambers and
      Tzavidis (). The key target of this approach to small area estimation is to
      obtain reliable and outlier robust estimates avoiding at the same time the need
      for strong parametric assumptions. This approach, however, does not allow for the
      use of unit level survey weights, making questionable the design consistency of
      the estimators unless the sampling design is self-weighting within small areas.
      In this paper, we adopt a model-assisted approach and construct design consistent
      small area estimators that are based on the M-quantile small area model. Analytic
      and bootstrap estimators of the design-based variance are discussed. The proposed
      estimators are empirically evaluated in the presence of complex sampling designs.

PMID- 24123146
TI  - Skin uptake and clearance of ciclopirox following topical application.
AB  - The assessment of skin uptake and clearance are important to determine the
      efficiency and systemic safety of dermatological formulations. The objective of
      this study was to assess the skin uptake, clearance and possible systemic
      delivery of ciclopirox following topical application in Wistar rats. In vitro
      studies (3 h) were carried out in excised pig skin to assess the permeation and
      retention capacity of ciclopirox in skin layers using gel formulations (1% and 2%
      w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by
      measuring the drug levels in the skin as a function of time post application
      (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in
      Wistar rats. The plasma drug concentrations were also determined in the same
      animals. In vitro data indicate the low permeability and high retention of
      ciclopirox in the stratum corneum. The DPK data observed indicate a higher Cmax
      value (175.43 +/- 25.62 MUg/cm2) and AUC (632.14 +/- 102.26 MUg.h/cm2) with the
      2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows
      first order kinetics with a short half-life (t1/2 ~2 h). The fraction of drug
      reaching the systemic circulation was found to be significantly low (~0.15% of
      the applied dose). A relation between the drug concentration in the skin layers
      and the plasma was observed with a short lag period. The topical availability of
      ciclopirox was found to be relatively low and endured rapid clearance with
      minimal systemic uptake.

PMID- 24123147
TI  - The road not taken or how I learned to love the liver: a personal perspective on
      hepatitis history.

PMID- 24123148
TI  - Synthesis and evaluation as antitumor agents of 1,4-naphthohydroquinone
      derivatives conjugated with amino acids and purines.
AB  - We report on the synthesis of two series of 1,4-naphthohydroquinone derivatives
      conjugated with amino acids (Gly, Ala, Phe, and Glu) and with substituted purines
      linked by an aliphatic chain. The compounds were obtained through Diels-Alder
      cycloaddition between myrcene and 1,4-benzoquinone and evaluated in vitro for
      their cytotoxicity (GI50 ) against cultured human cancer cells of A-549 lung
      carcinoma, HT-29 colon adenocarcinoma, and MCF-7 breast carcinoma. The GI50
      values found for some hydroquinone-amino acid and hydroquinone-purine hybrids
      against MCF-7 are in an activity range comparable to that of the reference drug
      doxorubicin. 

PMID- 24123149
TI  - Concurrent prescription rate of non-steroidal anti-inflammatory drugs with
      antihypertensive agents.

PMID- 24123151
TI  - The effects of strength, aerobic, and concurrent exercise on skeletal muscle
      damage in rats.
AB  - INTRODUCTION: In this study we examined oxidative stress and skeletal muscle
      damage resulting from acute strength, aerobic, or concurrent exercise in rats.
      METHODS: The animals were divided into control (C), strength (SE), aerobic (AE),
      and combined (CE) exercise groups. They were euthanized at 3 different time
      points (6, 24, and 48 h) after acute exercise. RESULTS: SE exercise rats had
      increased dichlorofluorescein oxidation at 6 h post-exercise and decreased
      superoxide dismutase activity at all time-points. Glutathione peroxidase activity
      and sulfhydryl levels were increased in the AE group at 48 h post-exercise. Serum
      lactate dehydrogenase activity was increased in the SE and CE groups at 24 h and
      in the AE group at 48 h. Echo intensity was elevated at 24 h for all groups.
      CONCLUSIONS: Forty-eight hours was sufficient for complete recovery from
      oxidative stress and muscle damage in the SE and CE groups, but not in the AE
      group.

PMID- 24123150
TI  - Fall risk and gait in Parkinson's disease: the role of the LRRK2 G2019S mutation.
AB  - Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine
      to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2
      (LRRK2) gene are generally believed to be clinically indistinguishable from
      patients with sporadic PD. There are, however, conflicting reports on the
      relationship between the mutation and the motor phenotype. We quantitatively
      compared gait and mobility in patients with PD carriers of the G2019S mutation to
      non-carrier patients with PD to better understand the genotype-phenotype
      relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50
      age, disease duration, and disease severity matched PD non-carriers were studied.
      An accelerometer quantified gait under three walking conditions: usual-walking,
      dual-tasking, and fast-walking. The Unified Parkinson's Disease Rating Scale
      classified patients into PD sub-types and the Timed Up and Go quantified mobility
      and fall risk. In all three walking conditions, gait variability was larger and
      the walking pattern was less consistent among the PD mutation carriers (P <
      0.016). The PD carriers also took longer to complete the Timed Up and Go (P =
      0.011) and were more likely to report having fallen in the previous year (P =
      0.018). 64% of the PD carriers were classified as belonging to the postural
      instability-gait-difficulty (PIGD) sub-type compared to only 17% of the PD non
      carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2
      gene is apparently associated with increased gait variability, an increased fall
      risk, and the PIGD sub-type. Therapeutic approach specifically designed to delay
      gait disturbances and falls may be justified in patients who carry the G2019S
      mutation.

PMID- 24123152
TI  - Tyrosine phosphatase STEP61 negatively regulates amyloid beta-mediated ERK/CREB
      signaling pathways via alpha7 nicotinic acetylcholine receptors.
AB  - Striatal-enriched phosphatase 61 (STEP61 ) plays an essential role in synaptic
      plasticity and has recently been implicated in neurodegenerative disease. Here we
      characterized a possible role of STEP61 in Alzheimer's disease (AD) pathology
      using a mouse model of AD (Tg-APPswe/PSEN1dE9, APP/PS1 mice) and an in vitro
      model of AD [cortical neurons treated with amyloid beta (Abeta)1-42 peptides].
      Our data indicate age-related elevation of STEP61 levels and the proportion of
      dephosphorylated STEP61 (active STEP61 ) in wild-type mice, which was enhanced in
      APP/PS1 mice. Furthermore, the increased STEP61 levels and active STEP61 were
      observed in the hippocampus and cortex from 12-month-old APP/PS1 mice and in
      Abeta1-42 -treated cortical neurons. An alpha7 nicotinic acetylcholine receptors
      (nAChRs) antagonist, alpha-bungarotoxin (BTX), inhibited the Abeta1-42 -induced
      increase of STEP61 expression and activation. In addition, extracellular signal
      regulated kinase 1/2 (ERK1/2) and cAMP response element binding (CREB) were
      impaired in Abeta1-42 -treated cortical neurons, and knockdown of STEP61 enhanced
      the activation of ERK1/2 and CREB. Collectively, these findings indicate two
      alternate pathological pathways effecting STEP61 regulation in AD. First, Abeta
      regulating STEP61 activity is mediated by Abeta binding to alpha7 nAChRs. Second,
      STEP61 negatively regulates Abeta-mediated ERK/CREB pathway, an important
      signaling cascade involved in memory formation.

PMID- 24123154
TI  - Predictive factors for latency period and a prognostic model for survival in
      patients with therapy-related acute myeloid leukemia.
AB  - Therapy-related acute myeloid leukemia (t-AML) is an increasingly recognized
      sequela in patients receiving chemotherapy or radiotherapy for a primary
      malignancy or autoimmune disease. This study assessed factors related to the
      latency period (LP) between the antecedent disorder (AD) and t-AML diagnosis and
      developed a comprehensive prognostic model to predict overall survival (OS). We
      evaluated a cohort of newly diagnosed t-AML patients treated with cytarabine
      based induction therapy from 2001 to 2011. Multivariable linear and proportional
      hazards models were used to assess the impact of different classes of
      chemotherapy on the LP and to identify independent prognostic factors for OS. Of
      730 treated AML patients, 58 (7.9%) had t-AML. Median LP to t-AML was 5.6 years
      (range, 0.5-38.4). 64% of patients achieved CR and median OS was 10.7 months.
      Independent prognostic factors of short LP were age at AD (P < 0.0001) and prior
      treatment with mitotic inhibitors (P = 0.05). Unfavorable cytogenetics (P =
      0.004), antecedent hematologic or autoimmune disease (P = 0.01), age >60 (P =
      0.03), and platelet count <30,000 MUL (P = 0.04) at the time of t-AML diagnosis
      were prognostic for inferior OS. A prognostic model using these factors was
      developed that risk stratified t-AML patients into two groups: favorable and
      unfavorable. Patients in the favorable group had a median OS of 37.6 months
      compared with 6.4 months in patients comprising the unfavorable group (P <
      0.0001). Multicomponent prognostic models integrating disease or treatment
      related covariates can help better understand how t-AML evolves; and can be
      clinically useful in risk stratifying t-AML patients undergoing induction
      therapy.

PMID- 24123153
TI  - Free-breathing cardiac MR stress perfusion with real-time slice tracking.
AB  - PURPOSE: To develop a free-breathing cardiac MR perfusion sequence with slice
      tracking for use after physical exercise. METHODS: We propose to use a leading
      navigator, placed immediately before each 2D slice acquisition, for tracking the
      respiratory motion and updating the slice location in real-time. The proposed
      sequence was used to acquire CMR perfusion datasets in 12 healthy adult subjects
      and 8 patients. Images were compared with the conventional perfusion (i.e.,
      without slice tracking) results from the same subjects. The location and geometry
      of the myocardium were quantitatively analyzed, and the perfusion signal curves
      were calculated from both sequences to show the efficacy of the proposed
      sequence. RESULTS: The proposed sequence was significantly better compared with
      the conventional perfusion sequence in terms of qualitative image scores. Changes
      in the myocardial location and geometry decreased by 50% in the slice tracking
      sequence. Furthermore, the proposed sequence had signal curves that are smoother
      and less noisy. CONCLUSION: The proposed sequence significantly reduces the
      effect of the respiratory motion on the image acquisition in both rest and stress
      perfusion scans.

PMID- 24123155
TI  - HIV, HBV, and HCV molecular epidemiology among trans (transvestites,
      transsexuals, and transgender) sex workers in Argentina.
AB  - Commercial sex work is frequent among male-to-female transvestites, transsexuals
      and transgenders in Argentina, leading to high susceptibility to HIV, HBV, and
      HCV among other sexually transmitted infections. In a global context of scarce
      data on the trans sex workers population, this study was aimed to study the
      genomic characterization of these viruses. Plasma presence of HIV, HBV, and HCV
      genomic material was evaluated in samples from 273 trans sex workers. Genomic
      sequences of HIV-gag, pol, and vif-vpu genes, HBV-S gene, and HCV-5'UT and NS5B
      genes were obtained. Molecular characterization involved phylogenetic analysis
      and several in silico tools. Resistance-associated mutations in HIV and HBV pol
      genes were also analyzed. The HIV genomic characterization in 62 trans sex
      workers samples showed that 54.8% of the isolates corresponded to BF intersubtype
      recombinants, and 38.7% to subtype B. The remaining were classified as subtypes C
      (4.8%) and A (1.6%). HBV and HCV co-infection prevalence among HIV positive trans
      sex workers yielded rates of 3.2% and 6.5% respectively. Drug resistance
      associated mutations were found in 12/62 (19%) HIV pol sequences, but none among
      HBV. Based on phylogenetic relationships, HIV isolates characterized as subtypes
      BF and B appeared intermingled with those from other high-risk groups. Despite
      trans sex workers declared not to have received antiviral treatment, complex drug
      resistance-associated mutation patterns were found in several HIV isolates.
      Planned prevention, screening, and treatment are needed to reduce further
      transmission and morbidity.

PMID- 24123156
TI  - Protein docking using case-based reasoning.
AB  - Protein docking algorithms aim to calculate the three-dimensional (3D) structure
      of a protein complex starting from its unbound components. Although ab initio
      docking algorithms are improving, there is a growing need to use homology
      modeling techniques to exploit the rapidly increasing volumes of structural
      information that now exist. However, most current homology modeling approaches
      involve finding a pair of complete single-chain structures in a homologous
      protein complex to use as a 3D template, despite the fact that protein complexes
      are often formed from one or more domain-domain interactions (DDIs). To model 3D
      protein complexes by domain-domain homology, we have developed a case-based
      reasoning approach called KBDOCK which systematically identifies and reuses
      domain family binding sites from our database of nonredundant DDIs. When tested
      on 54 protein complexes from the Protein Docking Benchmark, our approach provides
      a near-perfect way to model single-domain protein complexes when full-homology
      templates are available, and it extends our ability to model more difficult cases
      when only partial or incomplete templates exist. These promising early results
      highlight the need for a new and diverse docking benchmark set, specifically
      designed to assess homology docking approaches. 

PMID- 24123157
TI  - N-methyl-2-pyrrolidonium methyl sulfonate acidic ionic liquid as a new dynamic
      coating for separation of basic proteins by capillary electrophoresis.
AB  - A simple and economical CE method has been developed for the analysis of four
      model basic proteins by employing N-methyl-2-pyrrolidonium methyl sulfonate ionic
      liquid (IL) as the dynamic coating material based on the interaction of both
      between electrostatic attraction and hydrogen bond, and between the organic
      cations of IL and the inner surface of bare fused-silica capillary. The N-methyl
      2-pyrrolidonium-based IL modified capillary not only generated a stable
      suppressed electroosmotic flow, but also effectively eliminated the wall
      adsorption of proteins. Several important parameters such as the IL
      concentration, pH values, and concentrations of the background electrolyte were
      optimized to improve the separation of basic proteins. Consequently, under the
      optimum separation conditions, a satisfied separation of basic proteins including
      lysozyme, cytochrome c, ribonuclease A, and alpha-chymotrypsinogen A with
      theoretical plates ranging from 2.09 * 10(5) to 4.48 * 10(5) plates/m had been
      accomplished within 15 min. The proposed method first illustrated the effect of
      hydrogen bond between coating material and inner capillary surface on the
      coating, which should be a new strategy to design and select more effective
      coating materials to form more stable coatings in CE. 

PMID- 24123159
TI  - Cortical limb myoclonus in pathologically proven progressive supranuclear palsy.

PMID- 24123160
TI  - The effects of prolapse surgery on vaginal wall sensibility, vaginal
      vasocongestion, and sexual function: a prospective single centre study.
AB  - AIMS: Prolapse surgery has been shown to positively alter body image and decrease
      pelvic floor symptoms, hereby possibly improving sexual function. However, the
      surgical trauma itself may adversely affect sexual function, by damaging vaginal
      innervation and vascularization. The aim of this study is to evaluate the effects
      of vaginal prolapse surgery on vaginal vasocongestion, vaginal wall sensibility,
      and sexual function. METHODS: A prospective study was performed, including
      patients scheduled for vaginal prolapse surgery. Participants underwent
      measurements before and 6 months after surgery, during non-erotic and erotic
      visual stimuli. Measurements were performed using a vaginal combi-probe which
      includes vaginal photoplethysmography to assess vaginal pulse amplitude (VPA)
      (representing vaginal vasocongestion), and four pulse-generating electrodes to
      measure vaginal wall sensibility (representing vaginal innervation). Sexual
      function was assessed using validated questionnaires (FSFI, FSDS-R, SSAQ).
      RESULTS: Twenty-nine women were included, 24 (83%) completed the 6 months follow
      up. VPA analysis showed a significant reduction in vaginal vasocongestion during
      sexual stimulation post-operatively (pre-op 2.4 mV (SD 2.5) vs. post-op 1.7 mV
      (SD 2.4), P = 0.05). Vaginal wall sensibility in the cranial posterior vaginal
      wall was significantly reduced after surgery (pre-op 13.3 mA vs. post-op 17.5 mA,
      P < 0.05). Vaginal wall sensibility in the other three locations was not affected
      by surgery. Sexual function as assessed with questionnaires, was not
      significantly affected. CONCLUSION: Prolapse surgery negatively impacted levels
      of vaginal vasocongestion during erotic stimuli as well as vaginal wall
      sensibility in the cranial posterior wall. Future studies are needed to tease out
      if these changes in physiological factors are relevant for subjective sexual
      function.

PMID- 24123161
TI  - Factors influencing the electrokinetic injection of oligonucleotides in capillary
      gel electrophoresis when using laser-induced fluorescence detection.
AB  - Capillary gel electrophoresis (CGE) is a powerful tool for the analysis of
      oligonucleotides owing to its extraordinary resolving power. However, the only
      feasible injection mode for CGE, electrokinetic injection, can cause bias of the
      injected amount and thus reproducibility issues for CGE methods. Although the
      source of the bias in electrokinetic injection for analysis of small molecules by
      capillary zone electrophoresis has long been identified, there are very few
      studies on electrokinetic injection issues for biological molecules analyzed by
      CGE. In this study, we report three issues related to electrokinetic injection
      for oligonucleotides. First, the relationship between the injection amount and
      the sample solution resistance is not always linear for oligonucleotides, as has
      been observed for small molecules. Second, the injecting water prior to an
      oligonucleotide sample dramatically improves the reproducibility of both the
      injected amount and resolution through a 'stacking-like' mechanism. Third,
      optimizing the gel concentration dramatically increases the amount of
      oligonucleotide that is injected into the column.

PMID- 24123158
TI  - Glial influence on the blood brain barrier.
AB  - The Blood Brain Barrier (BBB) is a specialized vascular structure tightly
      regulating central nervous system (CNS) homeostasis. Endothelial cells are the
      central component of the BBB and control of their barrier phenotype resides on
      astrocytes and pericytes. Interactions between these cells and the endothelium
      promote and maintain many of the physiological and metabolic characteristics that
      are unique to the BBB. In this review we describe recent findings related to the
      involvement of astroglial cells, including radial glial cells, in the induction
      of barrier properties during embryogenesis and adulthood. In addition, we
      describe changes that occur in astrocytes and endothelial cells during injury and
      inflammation with a particular emphasis on alterations of the BBB phenotype.

PMID- 24123162
TI  - Discovery of 2-phenyl-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)acetamide
      derivatives as apoptosis inducers via the caspase pathway with potential
      anticancer activity.
AB  - In the current research of medicinal chemistry, apoptosis induction is one of the
      novel strategies for the development and discovery of novel anticancer
      therapeutics. In the present study, a new series of 1,3,4-thiadiazole derivatives
      (4a-4p) were synthesized and their in vitro anticancer activities were evaluated
      against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and
      SKNMC (neuroblastoma). These cell lines were utilized in MTT assays and the
      obtained results were compared to doxorubicin. Apoptosis induction was also
      investigated through exploration of the activation of caspases 3, 8, and 9.
      According to the obtained results, compounds 4b (3-Cl) and 4c (4-Cl) demonstrated
      the best caspase activation. In fact, compounds 4b and 4c enhanced the activity
      of caspases 3 and 9 in the MCF7 cell line. 

PMID- 24123163
TI  - Release of feruloylated oligosaccharides from wheat bran through submerged
      fermentation by edible mushrooms.
AB  - Wheat bran, a by-product of the flour industry, is believed to be a raw material
      for the production of feruloylated oligosaccharides (FOs) because of its high
      content of conjiont ferulic acid (FA). Studies were carried out to identify
      edible mushrooms that are able to release FOs from wheat bran. All the six tested
      mushrooms (Pleurotus ostreatus, Hericium erinaceum, Auricularia auricula,
      Cordyceps militaris, Agrocybe chaxingu, and Ganoderma lucium) were found to
      release FOs, and Agrocybe chaxingu had the highest yield, reaching 35.4 uM in
      wheat bran broth. Enzymes detection showed that these species secreted
      extracellular enzymes during fermentation, including cellulase and xylanase.
      Agrocybe chaxingu secreted the significant amount of xylanase (180 mU ml(-1) ),
      which was responsible for the release of FOs from wheat bran, while Hericium
      erinaceum secreted FA esterase which could disassemble FOs. 

PMID- 24123164
TI  - The meaning of (quality of) life in patients with eating disorders: a comparison
      of generic and disease-specific measures across diagnosis and outcome.
AB  - OBJECTIVE: Compare general and disease-specific health-related quality of life
      (HRQoL) among female patients with an eating disorder (ED). METHOD: Female
      patients (n = 221; 95.3% Caucasian; 94.0% never married) completed the Medical
      Outcome Short Form Health Survey (SF-36) and Eating Disorders Quality of Life
      (EDQoL) as part of a study of treatment outcomes. Multivariate regression models
      were used to compare HRQoL differences across initial ED diagnosis (85 AN-R, 19
      AN-B/P, 27 BN, 90 EDNOS) and ED diagnostic classification at time of outcome
      assessment (140 no ED, 38 subthreshold ED, 43 full threshold ED). RESULTS: There
      were no significant differences across ED diagnosis at initial assessment on
      either of the SF-36 Component Summary scores. However, patients with AN-B/P
      scored poorer on the work/school EDQoL subscales than other ED diagnoses, and on
      the psychological EDQoL subscale compared to AN-R and EDNOS. At outcome
      assessment, comparisons across full threshold, subthreshold and no ED
      classification indicated that those with no ED reported better HRQoL than those
      with full threshold ED on the SF-36 Mental Components Summary and three of four
      EDQoL subscales. Furthermore, those with no ED reported better psychological
      HRQoL than those with subthreshold ED. DISCUSSION: Disease-specific HRQOL
      measures are important to use when comparing HRQoL in ED patients across
      treatment and outcome, and may have the sensitivity to detect meaningful
      differences by diagnosis more so than generic instruments. EDQoL scores from
      patients remitted from symptoms approach but do not reach scores for unaffected
      college females; thus, treatment should continue until quality of life is
      restored.

PMID- 24123165
TI  - Visualizing the flow of evidence in network meta-analysis and characterizing
      mixed treatment comparisons.
AB  - Network meta-analysis techniques allow for pooling evidence from different
      studies with only partially overlapping designs for getting a broader basis for
      decision support. The results are network-based effect estimates that take
      indirect evidence into account for all pairs of treatments. The results
      critically depend on homogeneity and consistency assumptions, which are sometimes
      difficult to investigate. To support such evaluation, we propose a display of the
      flow of evidence and introduce new measures that characterize the structure of a
      mixed treatment comparison. Specifically, a linear fixed effects model for
      network meta-analysis is considered, where the network estimates for two
      treatments are linear combinations of direct effect estimates comparing these or
      other treatments. The linear coefficients can be seen as the generalization of
      weights known from classical meta-analysis. We summarize properties of these
      coefficients and display them as a weighted directed acyclic graph, representing
      the flow of evidence. Furthermore, measures are introduced that quantify the
      direct evidence proportion, the mean path length, and the minimal parallelism of
      mixed treatment comparisons. The graphical display and the measures are
      illustrated for two published network meta-analyses. In these applications, the
      proposed methods are seen to render transparent the process of data pooling in
      mixed treatment comparisons. They can be expected to be more generally useful for
      guiding and facilitating the validity assessment in network meta-analysis.

PMID- 24123166
TI  - Interferon regulatory factor 3 constrains IKKbeta/NF-kappaB signaling to
      alleviate hepatic steatosis and insulin resistance.
AB  - Obesity and related metabolic diseases associated with chronic low-grade
      inflammation greatly compromise human health. Previous observations on the roles
      of interferon regulatory factors (IRFs) in the regulation of metabolism prompted
      investigation of the involvement of a key family member, IRF3, in metabolic
      disorders. IRF3 expression in the liver is decreased in animals with diet-induced
      and genetic obesity. The global knockout (KO) of IRF3 significantly promotes
      chronic high-fat diet (HFD)-induced hepatic insulin resistance and steatosis; in
      contrast, adenoviral-mediated hepatic IRF3 overexpression preserves glucose and
      lipid homeostasis. Furthermore, systemic and hepatic inflammation, which is
      increased in IRF3 KO mice, is attenuated by the overexpression of hepatic IRF3.
      Importantly, inhibitor of nuclear factor kappa B kinase beta subunit / nuclear
      factor kappa B (IKKbeta/NF-kappaB) signaling is repressed by IRF3, and hepatic
      overexpression of the inhibitor of kappaB-alpha (IkappaBalpha) reverses HFD
      induced insulin resistance and steatosis in IRF3 KO mice. Mechanistically, IRF3
      interacts with the kinase domain of IKKbeta in the cytoplasm and inhibits its
      downstream signaling. Moreover, deletion of the region of IRF3 responsible for
      the IRF3/IKKbeta interaction inhibits the capacity of IRF3 to preserve glucose
      and lipid homeostasis. CONCLUSION: IRF3 interacts with IKKbeta in the cytoplasm
      to inhibit IKKbeta/NF-kappaB signaling, thus alleviating hepatic inflammation,
      insulin resistance, and hepatic steatosis.

PMID- 24123167
TI  - The 'who are all these people?' study.
AB  - BACKGROUND: Overcrowding of emergency departments (EDs) adversely affects the
      delivery of emergency care and results in increased patient mortality. OBJECTIVE
      AND METHODS: To examine what contributes to the ED crowd and to specifically
      examine the patient associated population. The ED in which the research was
      performed is consistently one of the most overcrowded in Ireland. RESULTS: On
      average 66.7% of the patients in the ED during the study period were boarded
      awaiting a hospital bed following full processing by the ED staff and agreement
      by the on-call team that admission was required. The most overcrowded part of the
      department was the majors area. In this area 55.5% of those present were
      patients, visitors accounted for 16.6% of occupants, nursing staff 11%, on-call
      teams 7% and the ED doctors 6.3%. CONCLUSIONS: Knowing who the people in the
      crowd are helps to guide management decisions about how the crowd might be
      reduced. Our department now has a strict accompanying person/visitor policy that
      limits the number of visitors to patients and limits visiting times for those
      relatives with a patient who is experiencing a prolonged stay in the ED.

PMID- 24123168
TI  - No gender-related bias in acute musculoskeletal pain management in the emergency
      department.
AB  - INTRODUCTION: Patients' gender remains a contributor for bias in pain management.
      Implementation of standardised analgesic protocols has been shown to minimise
      bias in analgesic care. The purpose of this study was to assess whether gender
      related bias in pain management exists in our emergency department (ED) setting,
      where a standardised pain management protocol based on patients' subjective pain
      rating is routinely used. METHODS: Pain management measures (ie, analgesia
      administration, waiting time for analgesia, pain relief and patients'
      satisfaction) were prospectively assessed in 328 patients (150 women and 178 men,
      average age 36+/-18 years) who were treated in our ED for acute musculoskeletal
      pain. RESULTS: Patients' subjective pain rating on arrival were similar for men
      and women (59+/-24 mm vs 61+/-26 mm, respectively; p=0.47). Interestingly,
      physicians using the same scale assessed the women's pain level to be higher than
      that of men (75+/-25 mm vs 63+/-22 mm, respectively; p<0.001) and higher than
      that of women's subjective pain rating (75+/-25 mm vs 61+/-26 mm respectively;
      p<0.001). Nevertheless, the rates of analgesia administration, waiting time for
      analgesia, pain relief and patient satisfaction were similar for both genders.
      Physicians' own gender did not affect analgesic care. CONCLUSIONS: Our findings
      suggest that a standardised pain management protocol based on patients'
      subjective pain rating may reduce gender-related bias in acute musculoskeletal
      pain management.

PMID- 24123169
TI  - The association between on-scene blood pressure and early neurological
      deterioration in patients with spontaneous intracerebral haemorrhage.
AB  - OBJECTIVE: To determine whether on-scene BP is associated with early neurological
      deterioration (END) in patients with spontaneous intracerebral haemorrhage
      (SICH). METHODS: This retrospective cohort study enrolled consecutive ambulance
      transported adult SICH patients treated at our emergency department (ED) from
      January 2007 through December 2012. END was defined as a >=2-point decrease in
      GCS within 24 h of ED arrival. The exact relationship between on-scene BP and END
      was assessed using multiple logistic regression analyses for adjusting age,
      gender, Charlson Index, aspirin use, smoking, elapsed time, consciousness level
      on ED arrival, haematoma size, intraventricular extension, midline shift and
      infratentorial ICH. We further calculated the -2 log-likelihood decrease for each
      regression model incorporated with the BP values measured at different times to
      compare model fitness. RESULTS: After adjusting for the covariates, on-scene
      systolic BP (by 10 mm Hg incremental: OR = 1.126, 95% CI 1.015 to 1.265),
      diastolic BP (by 10 mm Hg incremental: OR=1.146, 95% CI 1.019 to 1.303) and mean
      arterial pressure (MAP) (by 10 mm Hg incremental: OR=1.225, 95% CI 1.057 to
      1.443) were significantly associated with END; adding on-scene MAP into the
      regression model yielded the highest model fitness increase. Adding on-scene BPs
      into the regression model yielded higher model fitness increase than adding ED
      and admission BPs. CONCLUSIONS: Few on-scene BP indices were associated with
      neuroworsening within 24 h after ED arrival in non-comatose SICH patients.
      Compared with BP measured on ED arrival or admission, on-scene BP had a stronger
      correlation with END.

PMID- 24123170
TI  - Inaugural prehospital care programme: conception, development and delivery.

PMID- 24123171
TI  - An injured climber.
AB  - Climbing incidents present a myriad of challenges to prehospital teams.
      Management decisions are often influenced by factors including difficulties in
      accessing patients, limited available resources and safe egress from scenes. This
      case illustrates the importance of an adaptable and innovative approach to scene
      management and clinical decision making in such cases. 

PMID- 24123172
TI  - Evidence-based plastic surgery--"status quo".

PMID- 24123173
TI  - Drug-induced removal of nitrogen derivatives in urine: a new concept whose time
      has come.

PMID- 24123174
TI  - Immersive polymer assembly on immobilized particles for automated capsule
      preparation.
AB  - We report a versatile approach for polymer capsule preparation using immobilized
      particles, which are immersed into polymer solutions either manually or by using
      an automated robotic dipping machine. This technique produces polyelectrolyte
      capsules with improved retention over conventionally prepared capsules.
      Additionally, responsive hydrogel capsules of different diameter can be prepared
      simultaneously. 

PMID- 24123175
TI  - Water-selective excitation of short T2 species with binomial pulses.
AB  - PURPOSE: For imaging of fibrous musculoskeletal components, ultra-short echo time
      methods are often combined with fat suppression. Due to the increased chemical
      shift, spectral excitation of water might become a favorable option at ultra-high
      fields. Thus, this study aims to compare and explore short binomial excitation
      schemes for spectrally selective imaging of fibrous tissue components with short
      transverse relaxation time (T2 ). METHODS: Water selective 1-1-binomial
      excitation is compared with nonselective imaging using a sub-millisecond spoiled
      gradient echo technique for in vivo imaging of fibrous tissue at 3T and 7T.
      RESULTS: Simulations indicate a maximum signal loss from binomial excitation of
      approximately 30% in the limit of very short T2 (0.1 ms), as compared to
      nonselective imaging; decreasing rapidly with increasing field strength and
      increasing T2 , e.g., to 19% at 3T and 10% at 7T for T2 of 1 ms. In agreement
      with simulations, a binomial phase close to 90 degrees  yielded minimum signal
      loss: approximately 6% at 3T and close to 0% at 7T for menisci, and for ligaments
      9% and 13%, respectively. CONCLUSION: Overall, for imaging of short-lived T2
      components, short 1-1 binomial excitation schemes prove to offer marginal signal
      loss especially at ultra-high fields with overall improved scanning efficiency.

PMID- 24123176
TI  - Human papillomavirus type-specific persistence and recurrence after treatment for
      cervical dysplasia.
AB  - Human papillomavirus (HPV) infection is a necessary factor in the cervical cancer
      development. Also after treatment for cervical dysplasia, HPV can be present and
      promote the recurrence of cervical disease. In the present study, the aim was to
      perform a long-term follow-up on the ability of HPV testing with genotyping, as
      compared with cytology, to predict recurrence of high-grade cervical
      intraepithelial neoplasia and to evaluate the effectiveness of treatment with
      loop electrosurgical excision procedure (LEEP) conization. Cervical samples for
      HPV DNA testing and cytological analysis were obtained from 178 women with
      abnormal smears referred for treatment with LEEP conization. These women were
      scheduled for HPV DNA testing and Pap smears before and 3, 6, 12, 24, and 36
      months after treatment. Three years after treatment 3.1% (N = 4) of women were
      still persistently HPV-positive with the same type as had been detected at
      treatment. Recurrent or residual cervical intraepithelial neoplasia II+ in
      histopathology was found among 9 (5.1%) women during follow-up. All of these
      women had type-specific HPV-persistence (sensitivity 100% [95% CI 63-100%] and
      specificity 94.7% [89.8-97.4%]), but only 7/9 had abnormal cytology (sensitivity
      77.8% [40.2-96.1%] and specificity 94.7% [89.8-97.4%]). No recurrent or residual
      disease was found among women with any other patterns of HPV positivity (e.g.,
      type change or fluctuating positivity) (sensitivity 0% [95% CI 0-37.1%] and
      specificity 80.5% [73.5-86.0%]). In conclusion, only type-specific HPV
      persistence predicted recurrent or residual disease, and HPV genotyping appears
      useful to improve the specificity when using HPV testing in post-treatment follow
      up.

PMID- 24123177
TI  - "Reactive" response evaluation of primary human astrocytes after methylmercury
      exposure.
AB  - Astrocytes are actively involved in brain development, in mature CNS regulation,
      and in brain plasticity. They play a critical role in response to cerebral
      injuries and toxicants through a reaction known as "reactive gliosis," which is
      characterized by specific structural and functional features. A large amount of
      literature highlights the central role of astrocytes in mediating methylmercury
      (MeHg) neurotoxicity. In fact, mercury is the major neurotoxic pollutant that
      continues to arouse interest in research because of the severe risk it poses to
      human health. In this article, we focus on the action of MeHg on human astrocyte
      (HA) reactivity. We clearly demonstrate that MeHg induces a state of cellular
      suffering by promoting delayed and atypical astrocyte reactivity mediated by
      impairment of the proliferative and trophic component of the astrocyte together
      with an inflammatory state. This condition is generated by negative modulation of
      the major proteins of the filamentous network, which is manifested by the
      destabilization of astrocytic cytoarchitecture. Our data confirms the toxic
      effects of MeHg on HA reactivity and allows us to hypothesize that the
      establishment of this state of suffering and the delayed onset of a typical
      astrocytic reactivity compromise the main protective function of HA.

PMID- 24123178
TI  - Capillary electrophoresis as a tool for a cost-effective assessment of the
      activity of plant membrane enzyme chlorophyllase.
AB  - The potential of the capillary electrophoresis-based enzymatic assay has been
      demonstrated in case of a typical plant membrane enzyme - chlorophyllase. An
      efficient, automated and rapid semi-quantitative method has been developed, which
      allowed us to assess the activity of the enzyme via two strategies. Firstly, a
      reaction conducted in a vial placed directly on the sample tray was combined with
      the concomitant separation and detection of reagents. The method was used to
      monitor the reaction progress. Secondly, an on-line approach was applied by using
      an electrophoretically mediated mixing. The reaction was performed in-capillary,
      resulting in an extreme reduction of the reagent amounts required for a single
      run. Both methods were effective in the assessment of the activity of a membrane
      enzyme, a member of protein class known to pose experimental difficulties.

PMID- 24123179
TI  - Definition and classification of evaluation units for CASP10.
AB  - For the 10th experiment on Critical Assessment of the techniques of protein
      Structure Prediction (CASP), the prediction target proteins were broken into
      independent evaluation units (EUs), which were then classified into template
      based modeling (TBM) or free modeling (FM) categories. We describe here how the
      EUs were defined and classified, what issues arose in the process, and how we
      resolved them. EUs are frequently not the whole target proteins but the
      constituting structural domains. However, the assessors from CASP7 on combined
      more than one domain into 1 EU for some targets, which implied that the
      assessment also included evaluation of the prediction of the relative position
      and orientation of these domains. In CASP10, we followed and expanded this notion
      by defining multidomain EUs for a number of targets. These included 3 EUs, each
      made of two domains of familiar fold but arranged in a novel manner and for which
      the focus of evaluation was the interdomain arrangement. An EU was classified to
      the TBM category if a template could be found by sequence similarity searches and
      to FM if a structural template could not be found by structural similarity
      searches. The EUs that did not fall cleanly in either of these cases were
      classified case-by-case, often including consideration of the overall quality and
      characteristics of the predictions.

PMID- 24123180
TI  - Anconeus motor unit number estimates using decomposition-based quantitative
      electromyography.
AB  - INTRODUCTION: Motor unit number estimates (MUNEs) provide important information
      in health, aging, and disease, and can be determined using decomposition-enhanced
      spike-triggered averaging (DE-STA). Discrimination of surface-detected motor unit
      potentials (S-MUPs) has been limited to contractile forces of ?30% maximum
      voluntary contraction (MVC), which is insufficient to recruit a representative
      sample of the entire MU pool in most muscles. Unique features of the anconeus may
      permit MUNEs at high muscle activation levels. METHODS: In 10 men (25 +/- 3
      years), anconeus MUNEs were performed using DE-STA at 10%, 30%, and 50% root-mean
      square of MVC (RMS(MVC)). RESULTS: The mean compound muscle action potential of
      the anconeus was ?6 mV, and average S-MUP amplitudes were ?100 MUV, 145 MUV, and
      235 MUV at 10%, 30%, and 50% RMS(MVC), resulting in low average MUNEs of 58, 38,
      and 25, respectively. CONCLUSIONS: Elbow extensor force-EMG relationships suggest
      full recruitment of the anconeus MU pool at 50% RMS(MVC), thus providing a
      representative sample for MUNE.

PMID- 24123181
TI  - Corticosterone treatment results in enhanced release of peptidergic vesicles in
      astrocytes via cytoskeletal rearrangements.
AB  - While the effect of stress on neuronal physiology is widely studied, its effect
      on the functionality of astrocytes is not well understood. We studied the effect
      of high doses of stress hormone corticosterone, on two physiological properties
      of astrocytes, i.e., gliotransmission and interastrocytic calcium waves. To study
      the release of peptidergic vesicles from astrocytes, hippocampal astrocyte
      cultures were transfected with a plasmid to express pro-atrial natriuretic
      peptide (ANP) fused with the emerald green fluorescent protein (ANP.emd). The
      rate of decrease in fluorescence of ANP.emd on application of ionomycin, a
      calcium ionophore was monitored. Significant increase in the rate of calcium
      dependent exocytosis of ANP.emd was observed with the 100 nM and 1 MUM
      corticosterone treatments for 3 h, which depended on the activation of the
      glucocorticoid receptor. ANP.emd tagged vesicles exhibited increased mobility in
      astrocyte culture upon corticosterone treatment. Increasing corticosterone
      concentrations also resulted in concomitant increase in the calcium wave
      propagation velocity, initiated by focal ATP application. Corticosterone
      treatment also resulted in increased GFAP expression and F-actin rearrangements.
      FITC-Phalloidin immunostaining revealed increased formation of cross linked F
      actin networks with the 100 nM and 1 MUM corticosterone treatment. Alternatively,
      blockade of actin polymerization and disruption of microtubules prevented the
      corticosterone-mediated increase in ANP.emd release kinetics. This study reports
      for the first time the effect of corticosterone on gliotransmission via
      modulation of cytoskeletal elements. As ANP acts on both neurons and blood
      vessels, modulation of its release could have functional implications in
      neurovascular coupling under pathophysiological conditions of stress.

PMID- 24123182
TI  - The effectiveness of borneol on pharmacokinetics changes of four ginsenosides in
      Shexiang Baoxin Pill in vivo.
AB  - Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine, widely used for
      cardiovascular diseases in the clinic. Ginsenosides are important effective
      components in SBP, but their pharmacokinetic characteristics are still not known.
      In this paper, we studied the pharmacokinetics of ginsenoside Rb1, Rc, Re and Rg1
      in SBP and investigated the effect of borneol on the pharmacokinetic
      characteristic of ginsenosides based on an Agilent G6410A triple quadrupole LC/MS
      system. Results showed that the pharmacokinetic parameters of ginsenoside Rb1,
      Rc, Re and Rg1 in rat plasma after oral administration of SBP are significantly
      different with oral administration of SBP without Borneolum Syntheticum. Plasma
      pharmacokinetic profiles after oral administration of ginsenoside Rb1, Rc, Re,
      Rg1 and co-administration with borneol at three different ratios (10:1, 1:1 and
      1:10 ginsenoside vs borneol, w/w) were also determined. It was demonstrated that
      borneol can elevate the plasma concentration of ginsenosides after co
      admininstration.

PMID- 24123183
TI  - Wild-laid versus captive-laid eggs in the black-bellied sandgrouse: is there any
      effect on chick productivity?
AB  - Because survival in captivity is a significant determinant of birds available for
      release and reinforcement of wild populations, we aimed to identify sources of
      variation in mortality to assess potential impacts of management on chick
      productivity. We analyzed characteristics of Black-bellied Sandgrouse eggs
      collected from the wild and produced by captive pairs. Wild laid-eggs and pulled
      captive-laid eggs were incubated artificially and all chicks were hand-reared
      until seven weeks of age. Wild-laid eggs were significantly bigger, heavier, and
      denser than captive-laid eggs which showed a higher variability in size.
      Fertility, embryo mortality, and fertile egg hatchability were similar for wild
      laid and captive-laid eggs (67.92% vs. 68%; 15.62% vs. 15.7%, and 80.55% vs.
      84.44%, respectively). There were significant positive relationships between egg
      weigh/volume and chick hatch weight. Mortality of chicks hatched from wild-laid
      eggs was much lower than that of chicks from captive-laid eggs (19.44% vs. 60.5%)
      during the first week after hatching, but decreased and being nil from the third
      week. Heavier hatchlings from captive-laid eggs exhibited higher survival rates
      which is not the case of hatchlings from wild-laid eggs. These latter hatchlings
      had higher survival rates increasing with the age of eggs in relation with the
      period of natural incubation. The recommended age at which wild-laid eggs could
      be collected is at least 13 days for full chick survivability. We concluded that
      in our experimental captive breeding program of the Black-bellied Sandgrouse,
      productivity of viable hatchlings was much better from wild-laid eggs and as
      later as these were collected.

PMID- 24123184
TI  - Pallidal stimulation in atypical pantothenate kinase-associated
      neurodegeneration: six-year follow-up.

PMID- 24123185
TI  - Fatty intra-abdominal lymph nodes in chronic lymphocytic leukemia.

PMID- 24123186
TI  - Synthesis and pharmacological evaluation of novel tricyclic[2,1-f]theophylline
      derivatives.
AB  - The multireceptor strategy was implemented to obtain potential antipsychotics
      and/or antidepressants in a series of long-chain arylpiperazines bearing a
      tricyclic theophylline fragment. Their binding profile toward monoaminergic
      receptors (alpha1, 5-HT(1A), 5-HT(2A), 5-HT6, 5-HT7, D2, D3) was determined as
      well. The selected compounds 7 and 9 were tested in functional in vivo models and
      showed, like atypical antipsychotic drugs, presynaptic 5-HT(1A) receptor
      agonistic and postsynaptic 5-HT(1A), 5-HT(2A), and D2 receptor antagonistic
      activity.

PMID- 24123187
TI  - Improving the quality of clinical practice guidelines for clinicians and
      patients.

PMID- 24123188
TI  - Oral vaccination with inhibin DNA delivered using attenuated Salmonella
      choleraesuis for improving reproductive traits in mice.
AB  - The objective of this study was to examine the efficacy and safety of a novel
      inhibin vaccine containing inhibin alpha (1-32) fragments in mice. A recombinant
      plasmid pVAX-asd-IS was constructed by inserting recombinant inhibin alpha (1-32)
      and the hepatitis B surface antigen S into the plasmid in which the asd gene,
      rather than the kanamycin gene, was a selection marker. Ninety Kuming mice were
      divided into six groups consisting of 15 mice each. First group was (C1) injected
      with 200 ul of PBS, second (C2) received 1 * 10(10) CFU of crp(-) /asd(-)
      C500/pVAX-asd and served as vector control, third did not receive any treatment
      (C3), while fourth, fifth, and sixth group received 1 * 10(10) , 1 * 10(9) , 1 *
      10(8) CFU of the recombinant inhibin vaccine crp(-) /asd(-) C500/pVAX-asd-IS
      (group T1, T2, T3), respectively. Western blotting demonstrated that recombinant
      expressed inhibin protein possessed immune function and that this plasmid could
      replicate for up to 40 generations stably. Vaccination with this strain at a dose
      of 1 * 10(10) CFU/200 ul per mouse induced high anti-inhibin antibody levels,
      significantly increased large-follicle production in T1 group (p < 0.05) and
      average litter size (p > 0.05) compared with control groups. Integration studies
      showed no evidence of inhibin fusion gene integrated into mice's genome 2-month
      after immunization. These results suggest that the vaccine described in the
      present study may provide a safe method to improve reproductive traits in
      animals. A trend towards increased litter size and significant increase in large
      follicle population depict that this vaccine may have direct application in large
      animal industry. 

PMID- 24123189
TI  - Localization of impacted maxillary canines and root resorption of neighbouring
      teeth: a study assessing the diagnostic value of panoramic radiographs in two
      groups of observers.
AB  - OBJECTIVES: To assess the diagnostic value of panoramic views (2D) of patients
      with impacted maxillary canines by a group of trained orthodontists and oral
      surgeons, and to quantify the subjective need and reasons for further three
      dimensional (3D) imaging. MATERIALS AND METHODS: The study comprises 60 patients
      with panoramic radiographs (2D) and cone beam computed tomography (CBCT) scans
      (3D), and a total of 72 impacted canines. Data from a standardized questionnaire
      were compared within (intragroup) and between (intergroup) a group of
      orthodontists and oral surgeons to assess possible correlations and differences.
      Furthermore, the questionnaire data were compared with the findings from the CBCT
      scans to estimate the correlation within and between the two specialties.
      Finally, the need and reasons for further 3D imaging was analysed for both
      groups. RESULTS: When comparing questionnaire data with the analysis of the
      respective CBCT scans, orthodontists showed probability (Pr) values ranging from
      0.443 to 0.943. Oral surgeons exhibited Pr values from 0.191 to 0.946.
      Statistically significant differences were found for the labiopalatal location of
      the impacted maxillary canine (P = 0.04), indicating a higher correlation in the
      orthodontist group. The most frequent reason mentioned for the further need of 3D
      analysis was the labiopalatal location of the impacted canines. Oral surgeons
      were more in favour of performing further 3D imaging (P = 0.04). CONCLUSIONS:
      Orthodontists were more likely to diagnose the exact labiopalatal position of
      impacted maxillary canines when using panoramic views only. Generally, oral
      surgeons more often indicated the need for further 3D imaging.

PMID- 24123190
TI  - Minnesota multiphasic personality inventory-2 restructured form (MMPI-2-RF) scale
      score differences in bariatric surgery candidates diagnosed with binge eating
      disorder versus BMI-matched controls.
AB  - OBJECTIVE: Binge Eating Disorder (BED) is among the most common psychiatric
      disorders in bariatric surgery candidates. The Minnesota Multiphasic Personality
      Inventory-2 Restructured Form (MMPI-2-RF) is a broadband, psychological test that
      includes measures of emotional and behavioral dysfunction, which have been
      associated with BED behaviors in bariatric surgery candidates; however these
      studies have lacked appropriate controls. In the current study, we compared MMPI
      2-RF scale scores of bariatric surgery patients diagnosed with BED (BED+) with
      BMI-matched controls without BED (BED-). METHOD: Three-hundred and seven BED+
      participants (72.64% female and 67.87% Caucasian; mean BMI of 51.36 kg/m(2) [SD =
      11.94]) were drawn from a large, database (N = 1304). Three-hundred and seven BED
      participants were matched on BMI and demographics (72.64% female, 68.63%
      Caucasian, and mean BMI of 51.30 kg/m(2) [SD = 11.70]). RESULTS: The BED+ group
      scored significantly higher on measures of Demoralization, Low Positive Emotions,
      and Dysfunctional Negative Emotions and scored lower on measures of Antisocial
      Behaviors, reflecting behavioral constraint. Optimal T-Score cutoffs were below
      the traditional 65 T score for several MMPI-2-RF scales. MMPI-2-RF externalizing
      measures also added incrementally to differentiating between the groups beyond
      the Binge Eating Scale (BES). DISCUSSION: BED+ individuals produced greater
      elevations on a number of MMPI-2-RF internalizing scales and externalizing
      scales. Use of the test in conjunction with a clinical interview and other self
      report data can further aid the clinician in guiding patients to appropriate
      treatment to optimize outcome.

PMID- 24123191
TI  - Bayesian random effects selection in mixed accelerated failure time model for
      interval-censored data.
AB  - In many medical problems that collect multiple observations per subject, the time
      to an event is often of interest. Sometimes, the occurrence of the event can be
      recorded at regular intervals leading to interval-censored data. It is further
      desirable to obtain the most parsimonious model in order to increase predictive
      power and to obtain ease of interpretation. Variable selection and often random
      effects selection in case of clustered data become crucial in such applications.
      We propose a Bayesian method for random effects selection in mixed effects
      accelerated failure time (AFT) models. The proposed method relies on the Cholesky
      decomposition on the random effects covariance matrix and the parameter-expansion
      method for the selection of random effects. The Dirichlet prior is used to model
      the uncertainty in the random effects. The error distribution for the accelerated
      failure time model has been specified using a Gaussian mixture to allow flexible
      error density and prediction of the survival and hazard functions. We demonstrate
      the model using extensive simulations and the Signal Tandmobiel Study((r)).

PMID- 24123192
TI  - Thermal cyclization of phenylallenes that contain ortho-1,3-dioxolan-2-yl groups:
      new cascade reactions initiated by 1,5-hydride shifts of acetalic H atoms.
AB  - A series of 2-(1,3-dioxolan-2-yl)phenylallenes that contained a range of
      substituents (alkyl, aryl, phosphinyl, alkoxycarbonyl, sulfonyl) at the cumulenic
      C3 position were prepared by using a diverse range of synthetic strategies and
      converted into their respective 1-(2-hydroxy)-ethoxy-2-substituted naphthalenes
      by smooth thermal activation in toluene solution. Electron-withdrawing groups at
      the C3 position accelerated these tandem processes, which consisted of 1) an
      initial hydride-like [1,5]-H shift of the acetalic H atom onto the central
      cumulene carbon atom; 2) a subsequent 6pi-electrocyclic ring-closure of the
      resulting reactive ortho-xylylenes; and 3) a final aromatization step with
      concomitant ring-opening of the 1,3-dioxolane fragment. If the 1,3-dioxolane ring
      of the starting allenes was replaced by a dimethoxymethyl group, the reactions
      led to mixtures of two disubstituted naphthalenes, which were formed by the
      migration of either the acetalic H atom or the methoxy group, with the latter
      migration occurring to a lesser extent. Two of the final 1,2-disubstituted
      naphthalenes were converted into their corresponding naphtho-fused
      dioxaphosphepine or dioxepinone through an intramolecular transesterification
      reaction. A DFT computational study accounted for the beneficial influence of the
      1,3-dioxolane fragment on the carbon atom from which the H-shift took place and
      also of the electron-withdrawing substituents on the allene terminus. Remarkably,
      in the processes that contained a sulfonyl substituent, the conrotatory 6pi
      electrocyclization step was of lower activation energy than the alternative
      disrotatory mode.

PMID- 24123193
TI  - Levodopa infusion improves impulsivity and dopamine dysregulation syndrome in
      Parkinson's disease.
AB  - BACKGROUND: Impulsivity and dopamine dysregulation syndrome are frequent
      complications of treatment in Parkinson's disease (PD). METHODS: We assessed the
      effect of jejunal levodopa infusion (JLI) on behavioral symptoms in 8 PD patients
      with motor complications and severe impulsivity and dopamine dysregulation
      syndrome (DDS), which had not be controlled before by adjusting oral medications.
      The infusion was delivered during 15 hours (daily dose 1007.2 +/- 302.5 mg) and
      stopped at night time. Patients were reassessed after 25 +/- 9 weeks of treatment
      with a stable dose of jejunal l-dopa. RESULTS: Off periods and dyskinesias
      decreased by 27% and 20,7% respectively, compared to baseline. DDS and all types
      of impulse control disorders (ICDs) improved in all patients, with nearly
      complete symptom resolution. Punding improved in all 5 patients but disappeared
      completely in only 1. CONCLUSIONS: Our experience suggests that l-dopa infusion
      has a positive effect on both motor complications and behavioral disorders. This
      treatment approach deserves further controlled studies.

PMID- 24123194
TI  - Timing of prophylactic hysterectomy-oophorectomy, mastectomy, and microsurgical
      breast reconstruction in BRCA1 and BRCA2 carriers.
AB  - BACKGROUND: BRCA (breast cancer susceptibility gene) carriers are at high risk
      for breast and ovarian malignancies, and often undergo prophylactic total
      abdominal hysterectomy-bilateral salpingo-oophorectomy (TAH-BSO), bilateral
      mastectomy, and microsurgical breast reconstruction. Our goal was to determine
      whether abdominal wall complications and flap choice are affected by the order of
      those procedures. METHODS: All BRCA carriers who underwent microsurgical breast
      reconstruction between 2007 and 2012 were studied. Abdominal wall complications
      and changes in the reconstructive plan were analyzed depending on the order of
      breast reconstruction and TAH-BSO. RESULTS: 442 patients underwent 612
      microsurgical breast reconstructions, 47 of whom were BRCA carriers. TAH-BSO was
      not a predictor of requiring mesh for fascial closure (OR 1.1, P = 0.8), or of
      hernia/bulge (OR = 1.6, P = 0.65). In five patients, a DIEP flap was altered to
      another flap as a direct result of prior TAH-BSO. Robotic TAH-BSO after breast
      reconstruction took longer to perform than before breast reconstruction (4.48 +/-
      1.00 hours vs. 3.23 +/- 0.70 hours, respectively, P = 0.023), due to abdominal
      wall tightness. However, none were converted to open. Full-muscle free TRAM flaps
      (compared to other flaps) and bilateral reconstructions (compared to unilateral)
      were the only predictors of mesh (OR = 9.85, P < 0.001 and 4.01, P < 0.001), and
      hernia/bulge (OR = 6.18, P < 0.001 and 2.13, P = 0.07). The order of TAH-BSO and
      breast reconstruction did not affect complications. CONCLUSIONS: In BRCA
      carriers, the order of TAH-BSO and microsurgical breast reconstruction does not
      affect complication rates. However, prior TAH-BSO may make DIEP flaps unfeasible,
      and robotic TAH-BSO after breast reconstruction takes longer, but can still be
      performed safely.

PMID- 24123195
TI  - Theoretical tests of the mechanical protection strategy in protein nanomechanics.
AB  - We provide theoretical tests of a novel experimental technique to determine
      mechanostability of proteins based on stretching a mechanically protected protein
      by single-molecule force spectroscopy. This technique involves stretching a
      homogeneous or heterogeneous chain of reference proteins (single-molecule
      markers) in which one of them acts as host to the guest protein under study. The
      guest protein is grafted into the host through genetic engineering. It is
      expected that unraveling of the host precedes the unraveling of the guest
      removing ambiguities in the reading of the force-extension patterns of the guest
      protein. We study examples of such systems within a coarse-grained structure
      based model. We consider systems with various ratios of mechanostability for the
      host and guest molecules and compare them to experimental results involving
      cohesin I as the guest molecule. For a comparison, we also study the force
      displacement patterns in proteins that are linked in a serial fashion. We find
      that the mechanostability of the guest is similar to that of the isolated or
      serially linked protein. We also demonstrate that the ideal configuration of this
      strategy would be one in which the host is much more mechanostable than the
      single-molecule markers. We finally show that it is troublesome to use the highly
      stable cystine knot proteins as a host to graft a guest in stretching studies
      because this would involve a cleaving procedure.

PMID- 24123196
TI  - High-efficiency encapsulation of Pt nanoparticles into the channel of carbon
      nanotubes as an enhanced electrocatalyst for methanol oxidation.
AB  - Pt-based nanostructures serving as anode catalysts for the methanol oxidation
      reaction (MOR) have been widely studied for many years. Nevertheless, challenging
      issues such as poor reaction kinetics and the short-term stability of the MOR are
      the main drawbacks of such catalysts and limit their applications. Herein, we
      have developed a facile approach to encapsulate Pt nanoparticles (NPs) inside the
      nanochannels of porous carbon nanotubes (CNTs; Pt-in-CNTs) as a new enhanced
      electrocatalytic material. The as-prepared CNTs offer simultaneously ordered
      diffusion channels for ions and a confinement effect for the NPs, which both
      facilitate the promotion of catalytic kinetics and avoid the Ostwald ripening of
      Pt NPs, thus leading to high activity and durable cycle life as an anode catalyst
      for MOR. This work provides a new approach for enhancing the stability and
      activity by optimizing the structure of the catalyst, and the Pt-in-CNTs
      represent the most durable catalysts ever reported for MOR. 

PMID- 24123197
TI  - Creatinine- versus cystatine C-based equations in assessing the renal function of
      candidates for liver transplantation with cirrhosis.
AB  - Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic
      predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an
      accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT
      patients. However, in these patients plasma creatinine (Pcr) is inaccurate and
      the place of serum cystatine C (CystC) is still debated. New GFR-predicting
      equations, based on standardized assays of Pcr and/or CystC, have been recently
      recommended in the general population but their performance in cirrhosis patients
      has been rarely studied. We evaluated the performance of the recently published
      Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI
      CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD
      and Hoek formulas) in cirrhosis patients referred for renal evaluation before
      OLT. Inulin clearance was performed in 202 consecutive patients together with the
      determination of Pcr and CystC with assays traceable to primary reference
      materials. The performance of the GFR-predicting equations was evaluated
      according to ascites severity (no, moderate, or refractory) and to hepatic and
      renal dysfunctions (MELD score  <= or >15 and KDOQI stages, respectively). In the
      whole population, CystC-based equations showed a better performance than Pcr
      based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation
      showed the best performance whatever the ascites severity and in presence of a
      significant renal dysfunction (GFR <60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based
      GFR predicting equations are not reliable in pre-OLT patients even when an IDMS
      traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to
      primary reference materials is performed and when a true measurement of GFR is
      not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended
      to evaluate renal function and for KDOQI staging.

PMID- 24123199
TI  - A hyperbranched conjugated polymer as the cathode interlayer for high-performance
      polymer solar cells.
AB  - An alcohol-soluble hyperbranched conjugated polymer HBPFN with a dimethylamino
      moiety is synthesized and used as a cathode interlayer. A PCE of 7.7% is obtained
      for PBDTTT-C-T/PC71 BM based solar cells. No obvious interfacial dipole is found
      at the interface between the active layer and HBPFN however, an interfacial
      dipole with the cathode could be one of the reasons for the enhanced performance.

PMID- 24123200
TI  - Streptomyces graminilatus sp. nov., isolated from bamboo litter.
AB  - A Gram-stain-positive, novel actinobacterium, designated strain JL-6(T), was
      isolated from the litter of a bamboo (Sasa borealis) forest in Damyang, Korea.
      Strain JL-6(T) had white-grey, smooth, cylindrical spores that were borne in
      straight, long spore-chains. The novel strain grew aerobically at 15-28  degrees
      C (optimum, 28  degrees C), pH 4.0-8.0 (optimum, pH 5.5) and with 0-1.5% (w/v)
      NaCl. The cell-wall peptidoglycan contained ll-diaminopimelic acid, glutamic
      acid, alanine and glycine. The predominant menaquinones were MK-9(H6) and MK
      9(H8). Whole-cell hydrolysates mainly contained glucose and ribose.
      Phosphatidylinositol and phosphatidylcholine were the diagnostic phospholipids.
      The G+C content of the genomic DNA was 72.8 mol%. Phylogenetic analysis based on
      16S rRNA gene sequences showed that strain JL-6(T) belonged to the genus
      Streptomyces with sequence similarities ranging from 97.3% to 98.3%. However, DNA
      DNA hybridization between JL-6(T) and the closest related strain, Streptomyces
      turgidiscabies, ATCC 700248(T) and other closely related species in the genus
      Streptomyces showed <50% relatedness. Based on these observations, strain JL-6(T)
      is proposed to represent a novel species of the genus Streptomyces, for which the
      name Streptomyces graminilatus sp. nov. is proposed. The type strain is JL-6(T) (
      = KACC 16470(T) = NBRC 108882(T)).

PMID- 24123201
TI  - Desulfatiferula berrensis sp. nov., a n-alkene-degrading sulfate-reducing
      bacterium isolated from estuarine sediments.
AB  - A novel sulfate-reducing bacterium designated strain BE2801(T) was isolated from
      oil-polluted estuarine sediments (Berre Lagoon, France). Cells were Gram-stain
      negative, motile, slightly curved or vibrioid rods. Optimal growth of strain
      BE2801(T) occurred at 30-32  degrees C, 0.5-1.5% NaCl (w/v) and pH 7.2-7.4.
      Strain BE2801(T) grew with C4 to C20 fatty acids or C12 to C20 n-alkenes as
      electron donors. Acetate and carbon dioxide were the oxidation products. The
      major cellular fatty acids were C16 : 0, C(16 : 1)omega7c and C(18 : 1)omega7.
      The DNA G+C content was 50.2 mol%. 16S rRNA and dsrAB gene sequence analysis
      indicated that strain BE2801(T) was a member of the family Desulfobacteraceae
      within the class Deltaproteobacteria. DNA-DNA hybridization with the most closely
      related taxon demonstrated 14.8 % relatedness. Based on phenotypic and
      phylogenetic evidence, strain BE2801(T) ( = DSM 25524(T) = JCM 18157(T)) is
      proposed to be a representative of a novel species of the genus Desulfatiferula,
      for which the name Desulfatiferula berrensis sp. nov. is suggested.

PMID- 24123202
TI  - Comparison of mobile-phase systems commonly applied in liquid chromatography-mass
      spectrometry of nucleic acids.
AB  - LC-MS represents an important technology for the qualitative and quantitative
      analysis of nucleic acids. For MS, ESI in negative ion mode is used. The
      chromatographic method of choice is ion-pair (IP) RP chromatography.
      Chromatographic separations are usually accomplished by gradients of an organic
      modifier in aqueous solutions of IP reagents. Commonly applied IP reagents are
      2.3 mM triethylamine/400 mM 1,1,1,3,3,3-hexafluoro-2-propanol (TEA/HFIP, pH 7.0)
      and 10-25 mM cyclohexyldimethylammonium acetate (CycHDMAA, pH 8.4). Direct
      comparison of mass spectrometric performance of the two solvent systems revealed
      that the TEA/HFIP system offers better detection sensitivity than the CycHDMAA
      system. This is mainly attributable to the depletion of HFIP during droplet
      formation and solvent evaporation. Removal of the anionic counterion facilitates
      oligonucleotide ionization, and the oligonucleotides are desorbed as highly
      charged ions into the gas phase. TEA/HFIP-based mobile phases are recommended for
      developing quantitative assays targeting defined oligonucleotides. The CycHDMAA
      system allows the formation of cyclohexyldimethylammonium adducts. These adducts
      are cleaved in the gas phase, and this decomposition gives rise to charge state
      reduction. Ammonium adduct formation is of particular importance in preventing
      adducting with metal ions. Thus, adducts with metal ions are efficiently
      suppressed with CycHDMAA. For the TEA/HFIP system, however, such adducting
      represents a severe problem particularly if large oligonucleotides are analyzed.
      Thus, CycHDMAA-based mobile phases are recommended for qualitative assays such as
      LC-MS-based genotyping. 

PMID- 24123203
TI  - Traumatic scratch injury in astrocytes triggers calcium influx to activate the
      JNK/c-Jun/AP-1 pathway and switch on GFAP expression.
AB  - Astrocyte activation is a hallmark of central nervous system injuries resulting
      in glial scar formation (astrogliosis). The activation of astrocytes involves
      metabolic and morphological changes with complex underlying mechanisms, which
      should be defined to provide targets for astrogliosis intervention. Astrogliosis
      is usually accompanied by an upregulation of glial fibrillary acidic protein
      (GFAP). Using an in vitro scratch injury model, we scratched primary cultures of
      cerebral cortical astrocytes and observed an influx of calcium in the form of
      waves spreading away from the wound through gap junctions. Using the calcium
      blocker BAPTA-AM and the JNK inhibitor SP600125, we demonstrated that the calcium
      wave triggered the activation of JNK, which then phosphorylated the transcription
      factor c-Jun to facilitate the binding of AP-1 to the GFAP gene promoter to
      switch on GFAP upregulation. Blocking calcium mobilization with BAPTA-AM in an in
      vivo stab wound model reduced GFAP expression and glial scar formation, showing
      that the calcium signal, and the subsequent regulation of downstream signaling
      molecules, plays an essential role in brain injury response. Our findings
      demonstrated that traumatic scratch injury to astrocytes triggered a calcium
      influx from the extracellular compartment and activated the JNK/c-Jun/AP-1
      pathway to switch on GFAP expression, identifying a previously unreported
      signaling cascade that is important in astrogliosis and the physiological
      response following brain injury.

PMID- 24123198
TI  - Gene-environment interactions in cancer epidemiology: a National Cancer Institute
      Think Tank report.
AB  - Cancer risk is determined by a complex interplay of genetic and environmental
      factors. Genome-wide association studies (GWAS) have identified hundreds of
      common (minor allele frequency [MAF] > 0.05) and less common (0.01 < MAF < 0.05)
      genetic variants associated with cancer. The marginal effects of most of these
      variants have been small (odds ratios: 1.1-1.4). There remain unanswered
      questions on how best to incorporate the joint effects of genes and environment,
      including gene-environment (G * E) interactions, into epidemiologic studies of
      cancer. To help address these questions, and to better inform research priorities
      and allocation of resources, the National Cancer Institute sponsored a "Gene
      Environment Think Tank" on January 10-11, 2012. The objective of the Think Tank
      was to facilitate discussions on (1) the state of the science, (2) the goals of G
      * E interaction studies in cancer epidemiology, and (3) opportunities for
      developing novel study designs and analysis tools. This report summarizes the
      Think Tank discussion, with a focus on contemporary approaches to the analysis of
      G * E interactions. Selecting the appropriate methods requires first identifying
      the relevant scientific question and rationale, with an important distinction
      made between analyses aiming to characterize the joint effects of putative or
      established genetic and environmental factors and analyses aiming to discover
      novel risk factors or novel interaction effects. Other discussion items include
      measurement error, statistical power, significance, and replication. Additional
      designs, exposure assessments, and analytical approaches need to be considered as
      we move from the current small number of success stories to a fuller
      understanding of the interplay of genetic and environmental factors. 

PMID- 24123204
TI  - MKKing the most of liver regeneration: an in vivo screen identifies the MKK4
      pathway as a suppressor of regeneration.

PMID- 24123205
TI  - It's not all in your head (or at least your brain): association of traumatic
      brain lesion presence and location with performance on measures of response bias
      in forensic evaluation.
AB  - This study examined the relationship between lesion presence and localization and
      performance on measures of cognitive response bias, specifically in individuals
      purporting to have a traumatic brain injury. Ninety-two participants, all of whom
      were involved in workers' compensation or personal injury litigation, were
      administered an extensive neuropsychological battery, including neuroimaging
      (magnetic resonance imaging and computed tomography), at a neuropsychiatric
      clinic in Lexington, KY. Those with evidence of intracranial injury on
      neuroimaging findings were placed in the head injury lesion litigation group and
      were coded based on the anatomical location and type of intracranial injury.
      Results demonstrated no significant relationships between lesion location and
      performance on performance validity tests (PVTs), as well as the Response Bias
      Scale of the Minnesota Multiphasic Personality Inventory-2 Restructured Form.
      Given the lack of research concerning lesions and performance validity tests,
      this study addresses important questions about the validity of PVTs as specific
      measures of response bias in patients who have structural changes secondary to
      traumatic brain injury.

PMID- 24123206
TI  - Detection of minimum activity fragment of a novel Cry7Ab3 protein specific to
      Henosepilachna vigintioctomaculata (Coleopteran: Coccinellidae).
AB  - Bacillus thuringiensis Cry7Ab3 toxin has insecticidal activity against larvae of
      Henosepilachna vigintioctomaculata. Cry7Ab3 toxin is solubilized under alkaline
      condition and activated by proteases within the larval gut. In order to assess
      the functions of the N- and C-terminal regions, several N- and C-terminal
      truncated forms of Cry7Ab3 were constructed. It was determined that amino acid
      removal at the N-terminal, which disrupt the alpha-helico structure, resulted in
      the inactivation of the protein. The deletion of 512 amino acids from the C
      terminus reduced the toxicity. However, the deletion of 481 amino acids from the
      C-terminus resulted in the highest activity. These findings directly demonstrated
      the critical roles of N- and C-terminal amino acids on the toxicity of Cry7Ab3. 

PMID- 24123207
TI  - Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and
      butyrylcholinesterase inhibitors.
AB  - In this study, we synthesized several imperatorin analogs using imperatorin and
      xanthotoxin as substrates. The anti-cholinesterase activities of all compounds
      were evaluated in in vitro experiments according to the modified Ellman's method.
      For each synthesized compound, IC50 values for both enzymes were established.
      Galantamine hydrobromide was used as a positive control in the enzymatic
      experiments. All active compounds showed selectivity toward butyrylcholinesterase
      (BuChE) rather than acetylcholinesterase. The most active ones were 8-(3
      methylbutoxy)-psoralen and 8-hexoxypsoralen with IC50 values for BuChE of around
      16.5 and 16.4 uM, respectively. The results of our study may be considered as the
      beginning of a search for potential anti-Alzheimer's disease drugs based on the
      structure of natural furocoumarins. 

PMID- 24123208
TI  - Modeling grade progression in an active surveillance study.
AB  - Prostate cancer grade, assessed with the Gleason score, describes how abnormal
      the tumor tissue and cells appear, and it is an important prognostic indicator of
      disease progression. Whether prostate tumors change grade is a question that has
      implications for screening and treatment. Empirical data on tumor grade over time
      have become available from men biopsied regularly as part of active surveillance
      (AS). However, biopsy (BX) grade is subject to misclassification. In this
      article, we develop a model that allows for estimation of the time of grade
      change while accounting for the misclassification error from BX grade. We use
      misclassification rates from studies of prostate cancer BXs followed by radical
      prostatectomy. Estimation of the transition times from true low-grade to high
      grade disease is conducted within a Bayesian framework. We apply our model to
      serial observations on BX grade among 627 cases enrolled in a cohort of AS
      patients at Johns Hopkins University who were biopsied annually and referred to
      treatment if there was any evidence of disease progression on BX. We consider
      different prior distributions for the time to true grade progression. The
      estimated likelihood of grade progression within 10 years of study entry ranges
      from 12% to 24% depending on the prior. We conclude that knowledge of rates of
      grade misclassification allows for determination of true grade progression rates
      among men with serial BXs on AS. Although our results are sensitive to prior
      specifications, they indicate that in a nontrivial fraction of the patient
      population, tumor grade can progress.

PMID- 24123209
TI  - Chronic exposure to pentachlorophenol alters thyroid hormones and thyroid hormone
      pathway mRNAs in zebrafish.
AB  - Pentachlorophenol (PCP) is frequently detected in the aquatic environment and has
      been implicated as an endocrine disruptor in fish. In the present study, 4-month
      old zebrafish (Danio rerio) were exposed to 1 of 4 concentrations of PCP (0.1, 1,
      9, and 27 ug/L) for 70 d. The effects of PCP exposure on plasma thyroid hormone
      levels, and the expression levels of selected genes, were measured in the brain
      and liver. The PCP exposure at 27 ug/L resulted in elevated plasma thyroxine
      concentrations in male and female zebrafish and depressed 3, 5, 3'
      triiodothyronine concentrations in males only. In both sexes, PCP exposure
      resulted in decreased messenger RNA (mRNA) expression levels of thyroid
      stimulating hormone beta-subunit (tshbeta) and thyroid hormone receptor beta
      (trbeta) in the brain, as well as increased liver levels of uridine
      diphosphoglucuronosyl transferase (ugt1ab) and decreased deiodinase 1 (dio1). The
      authors also identified several sex-specific effects of PCP exposure, including
      changes in mRNA levels for deiodinase 2 (dio2), cytosolic sulfotransferase (sult1
      st5), and transthyretin (ttr) genes in the liver. Environmental PCP exposure also
      caused an increased malformation rate in offspring that received maternal
      exposure to PCP. The present study demonstrates that chronic exposure to
      environmental levels of PCP alters plasma thyroid hormone levels, as well as the
      expression of genes associated with thyroid hormone signaling and metabolism in
      the hypothalamic-pituitary-thyroid (HPT) axis and liver, resulting in abnormal
      zebrafish development.

PMID- 24123210
TI  - 2,4-dinitrophenol partially alleviates ferrocyanide-induced toxicity in
      Drosophila melanogaster.
AB  - The toxicity of potassium ferrocyanide (PFC) and protective effects of 2,4
      dinitrophenol (DNP) under PFC treatment were tested on the Drosophila
      melanogaster model system. Fly larvae were raised on food supplemented with PFC
      at concentrations of 1.0 mM and mixtures with DNP in concentrations of 0.50 and
      1.25 mM, either alone or in combination with 1.0 mM PFC. Food supplementation
      with PFC decreased larvae viability or pupation height, whereas when larvae were
      fed by PFC and DNP combination the decrease was less pronounced. Larval exposure
      to PFC and mixtures of DNP and PFC lowered activities of aconitase. Larval
      treatment with PFC resulted in higher carbonyl protein, uric acid, and low
      molecular mass thiols content and higher activity of thioredoxin reductase in
      adult flies, while DNP in mixtures with PFC relieved these effects. Furthermore,
      treatment with PFC/DNP mixtures resulted in higher activities of superoxide
      dismutase and glutathione-S-transferase. It is proposed that PFC toxicity is
      mainly related to the cyanide and iron ions, released during its decomposition.
      The potential mechanisms of protective DNP effects against PFC toxicity are
      discussed. 

PMID- 24123213
TI  - Ischemia, immunosuppression, and SSEA-1-negative cells all contribute to tumors
      resulting from mouse embryonic stem cell-derived neural progenitor
      transplantation.
AB  - Neural progenitor cells (NPCs) derived from mouse embryonic stem (mES) cells can
      lead to tumors after transplantation. The cellular source of such tumors remains
      under debate. We investigated the tumor formation resulting from mES cell-derived
      NPCs in a rat stroke model and in nude mice. After 2 hr of ischemia and 48 hr of
      reperfusion, the NPCs were transplanted into the ischemic core of the xenogeneic
      rats. Four weeks after transplantation, the grafted cells were found to be viable
      at the border of the necrosis and had differentiated into neurons. Transplanted
      rats did not exhibit any behavioral improvement, because tumor formed in 90% of
      the animals. Immunosuppression facilitated tumor formation. Tumors were observed
      in 40% of normal rats after NPC transplantation when cyclosporin A was
      administered. Meanwhile, no tumor formation was observed without cyclosporin A.
      Ischemic damage also facilitated tumor formation, because NPCs gave rise to
      tumors in 90% of ischemic rats, a percentage significantly higher than that in
      intact rats, which was 40%. The SSEA-1-positive cells isolated from stage 4 are
      not exactly undifferentiated ES cells. They exhibited a marker gene transcription
      profile different from that of ES cells and did not form tumors in transplanted
      nude mice. The undifferentiated ES cells remaining after differentiation did not
      contribute to tumors either. First, the tumor formation rate resulting from
      undifferentiated ES cells in the brains of normal rats is 0%, significantly lower
      than that of NPCs. Second, transplanted NPCs that led to 100% tumors in nude mice
      contained approximately 1.5 * 10(3) Oct-4-positive cells; however, even 5 * 10(5)
      undifferentiated ES cells formed neoplasm only in 40% nude mice.

PMID- 24123214
TI  - Psychological well-being in out-patients with eating disorders: a controlled
      study.
AB  - OBJECTIVE: Positive functioning is widely neglected in research on eating
      disorders (EDs). The aim of this exploratory study was to assess psychological
      well-being (PWB) in out-patients with ED and in controls. METHOD: The authors
      assessed PWB in 245 out-patients with EDs [105 with bulimia nervosa (BN), 57 with
      anorexia nervosa (AN), and 83 with binge eating disorder (BED) who met DSM-IV-TR]
      and 60 controls. They tested whether PWB was associated with eating attitude test
      (EAT) scores and if such associations differed among ED groups while taking into
      account confounding variables. RESULTS: Significant differences between groups in
      all PWB scales were found. While individuals with BN reported significantly lower
      scores in all PWB dimensions than healthy controls, patients with BED scored
      significantly lower than controls in PWB autonomy, environmental mastery, and
      self-acceptance scales. Patients with AN showed similar scores to controls in all
      PWB dimensions, except for positive relationships and self-acceptance. In all ED
      groups, most PWB dimensions resulted significantly and negatively associated with
      EAT scales, except for AN where oral control was found to positively correlate
      with a high sense of purpose in life. All results were maintained even after
      adjusting for possible confounding variables. DISCUSSION: Patients with EDs
      reported an impairment in PWB. The paucity of PWB was not necessarily dependent
      on the presence of high levels of psychological distress and on the severity of
      the disorder. Such assessments may therefore yield a more comprehensive
      evaluation in this clinical population.

PMID- 24123215
TI  - A new role for IKK-alpha in hepatitis C virus-induced lipogenesis.

PMID- 24123216
TI  - Dysprosium complexes and their micelles as potential bimodal agents for magnetic
      resonance and optical imaging.
AB  - Six diethylene triamine pentaacetic acid (DTPA) bisamide derivatives
      functionalized with p-toluidine (DTPA-BTolA), 6-aminocoumarin (DTPA-BCoumA), 1
      naphthalene methylamine (DTPA-BNaphA), 4-ethynylaniline (DTPA-BEthA), p
      dodecylaniline (DTPA-BC12PheA) and p-tetradecyl-aniline (DTPA-BC14PheA) were
      coordinated to dysprosium(III) and the magnetic and optical properties of the
      complexes were examined in detail. The complexes consisting of amphiphilic
      ligands (DTPA-BC12PheA and DTPA-BC14PheA) were further assembled into mixed
      micelles. Upon excitation into the ligand levels, the complexes display
      characteristic Dy(III) emission with quantum yields of 0.3-0.5% despite the
      presence of one water molecule in the first coordination sphere. A deeper insight
      into the energy-transfer processes has been obtained by studying the
      photophysical properties of the corresponding Gd(III) complexes. Since the
      luminescence quenching effect is decreased by the intervention of non-ionic
      surfactant, quantum yields up to 1% are obtained for the micelles. The transverse
      relaxivity r2 per Dy(III) ion at 500 MHz and 310 K reaches a maximum value of
      27.4 s(-1) mM(-1) for Dy-DTPA-BEthA and 36.0 s(-1) mM(-1) for the Dy-DTPA
      BC12PheA assemblies compared with a value of 0.8 s(-1) mM(-1) for Dy-DTPA. The
      efficient T2 relaxation, especially at high magnetic field strengths, is
      sustained by the high magnetic moment of the dysprosium ion, the coordination of
      water molecules with slow water exchange kinetics and long rotational correlation
      times. These findings open the way to the further development of bimodal optical
      and magnetic resonance imaging probes starting from single lanthanide compounds.

PMID- 24123217
TI  - Adjusting for population stratification in a fine scale with principal components
      and sequencing data.
AB  - Population stratification is of primary interest in genetic studies to infer
      human evolution history and to avoid spurious findings in association testing.
      Although it is well studied with high-density single nucleotide polymorphisms
      (SNPs) in genome-wide association studies (GWASs), next-generation sequencing
      brings both new opportunities and challenges to uncovering population structures
      in finer scales. Several recent studies have noticed different confounding
      effects from variants of different minor allele frequencies (MAFs). In this
      paper, using a low-coverage sequencing dataset from the 1000 Genomes Project, we
      compared a popular method, principal component analysis (PCA), with a recently
      proposed spectral clustering technique, called spectral dimensional reduction
      (SDR), in detecting and adjusting for population stratification at the level of
      ethnic subgroups. We investigated the varying performance of adjusting for
      population stratification with different types and sets of variants when testing
      on different types of variants. One main conclusion is that principal components
      based on all variants or common variants were generally most effective in
      controlling inflations caused by population stratification; in particular,
      contrary to many speculations on the effectiveness of rare variants, we did not
      find much added value with the use of only rare variants. In addition, SDR was
      confirmed to be more robust than PCA, especially when applied to rare variants. 

PMID- 24123218
TI  - 3D graphene oxide-polymer hydrogel: near-infrared light-triggered active scaffold
      for reversible cell capture and on-demand release.
AB  - An active cell scaffold based on a graphene-polymer hydrogel has been
      successfully fabricated. The macroporous hydrogel can efficiently capture cells
      not only through the bioadhesive ligand RGD but also through on-demand release of
      cells with an NIR light stimulus. The latter process shows better dynamic control
      over cells than traditional passive-hydrogel-based cell depots. 

PMID- 24123219
TI  - A novel twist on molecular interactions between thioredoxin and nicotinamide
      adenine dinucleotide phosphate-dependent thioredoxin reductase.
AB  - The ubiquitous disulfide reductase thioredoxin (Trx) regulates several important
      biological processes such as seed germination in plants. Oxidized cytosolic Trx
      is regenerated by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent
      thioredoxin reductase (NTR) in a multistep transfer of reducing equivalents from
      NADPH to Trx via a tightly NTR-bound flavin. Here, interactions between NTR and
      Trx are predicted by molecular modelling of the barley NTR:Trx complex
      (HvNTR2:HvTrxh2) and probed by site directed mutagenesis. Enzyme kinetics
      analysis reveals mutants in a loop of the flavin adenine dinucleotide (FAD)
      binding domain of HvNTR2 to strongly affect the interaction with Trx. In
      particular, Trp42 and Met43 play key roles for recognition of the endogenous
      HvTrxh2. Trx from Arabidopsis thaliana is also efficiently recycled by HvNTR2 but
      turnover in this case appears to be less dependent on these two residues,
      suggesting a distinct mode for NTR:Trx recognition. Comparison between the
      HvNTR2:HvTrxh2 model and the crystal structure of the Escherichia coli NTR:Trx
      complex reveals major differences in interactions involving the FAD- and NADPH
      binding domains as supported by our experiments. Overall, the findings suggest
      that NTR:Trx interactions in different biological systems are fine-tuned by
      multiple intermolecular contacts.

PMID- 24123220
TI  - NMDA receptor couples Rac1-GEF Tiam1 to direct oligodendrocyte precursor cell
      migration.
AB  - Oligodendrocyte precursor cells (OPCs) originate from restricted regions of the
      brain and migrate into the developing white matter, where they differentiate into
      oligodendrocytes and myelinate axons in the central nervous system (CNS). The
      molecular mechanisms that orchestrate these long distance trips of OPCs to
      populate throughout the CNS are poorly understood. Emerging evidence has argued
      the expression of N-methyl-d-aspartic acid (NMDA) receptors (NMDARs) in
      oligodendrocyte lineage cells in vivo, but their physiological function remains
      elusive. We have previously demonstrated the expression and function of NMDARs in
      OPC differentiation and myelination/remyelination. Here, we show that NMDARs
      stimulation promotes OPC migration both by chemotaxis and chemokinesis as
      demonstrated by various cell migration systems including Boyden transwell, single
      cell, matrix-gel cell mass, and SVZ tissue explants assays. The pro-migration
      effect of NMDAR can be abolished by either pharmacological inhibition or shRNA
      knock down of the T lymphoma invasion and metastasis 1 (Tiam1), a Rac1 guanine
      nucleotide exchange factor (Rac1-GEF) which is coexpressed and interacts with
      NMDAR in OPCs. Moreover, NMDAR stimulation evokes cascade activation of the
      Tiam1/Rac1/ERK signaling pathway which mediates its effect on OPC migration. We
      also show that glutamate released from cultured cortical neuron promotes OPCs
      migration via NMDAR, and that antagonism of NMDAR or inhibition of Tiam1 blocks
      the endogenous glutamate-induced OPCs migration from SVZ to cortical plate in the
      embryonic brain slice culture. Thus, our result suggests a critical role of NMDAR
      in regulation of OPCs migration during CNS development by coupling to and
      activating the Tiam1/Rac1 pathway.

PMID- 24123222
TI  - In vitro evaluation of potential complexation between bovine insulin and bovine
      serum albumin.
AB  - The objective of this study was to examine the possible binding of bovine insulin
      (BI) with bovine serum albumin (BSA) to form a new potential diabetogenic
      irreversible complex protein. Several preparations of BSA and BI were prepared.
      Both capillary electrophoresis and spectrophotometric analysis were undertaken to
      test the possibility of complexation between BI and BSA. HPLC was used to test
      whether the potential complex of BI and BSA is reversible or irreversible. The
      optimum deviation between the real and calculated absorbances was observed at a
      BI/BSA ratio of 2. Moreover, the migration time of BI decreased substantially
      with increasing ratio of BI to BSA until it became almost constant at equal molar
      ratio of BI/BSA. While the majority of the 2:1 BI-BSA sample detached during the
      HPLC analysis, which confirms the reversible character of BI-BSA binding, the
      HPLC chromatogram also emphasizes the formation of an irreversible complexation
      between the two proteins. This study provides evidence of the formation of
      reversible and irreversible new BI-BSA complexes under physiological conditions.
      This highlights the importance of examining the possible diabetogenicity of BI
      BSA complex in genetically susceptible people.

PMID- 24123221
TI  - Hypercoagulability panel testing predicts thrombosis in neonates undergoing
      cardiac surgery.
AB  - Thrombosis contributes to morbidity and mortality in neonates following cardiac
      surgery. Alterations in hemostatic factors following cardiac surgery have been
      described, but there is no data correlating these changes with risk of thrombosis
      in neonates. The aim of this study is to predict thrombosis in neonates
      undergoing cardiac surgery by assessment of a panel of hypercoagulability
      markers. Neonates undergoing cardiac surgery were enrolled preoperatively and
      prospectively followed. Preoperative hypercoagulability panel testing included
      thrombin generation assay (TGA), immunoassays for antithrombin III, protein C,
      protein S, factor VIII, thrombin-activatable fibrinolytic inhibitor (TAFI),
      plasminogen activator inhibitor-1 (PAI-1), and cardiolipin antibody.
      Postoperative thrombosis was defined by clinical events (shunt thrombosis, limb
      ischemia, and stroke) or imaging (intravascular or intracardiac thrombus). Risk
      factors for thrombosis were assessed. One hundred neonates were enrolled in the
      study over a two-year period. The incidence of postoperative in-hospital
      thrombosis was 20%. The only significant clinical risk factor associated with
      thrombosis was the single ventricle physiology. Hypercoagulability factors
      associated with increased risk of thrombosis by univariate analysis were elevated
      PAI-1, TAFI, and TGA, and presence of anticardiolipin antibodies. Multivariable
      logistic regression analysis demonstrated that elevated PAI-1 (P = 0.015), TAFI
      (P = 0.028), and TGA (P = 0.007) were independent predictors of thrombosis.
      Hypercoagulability panel testing may help identify neonates at high risk for
      thrombosis following cardiac surgery. Future studies are warranted to determine
      if high risk patients benefit from targeted anticoagulation therapies.

PMID- 24123223
TI  - Nanotopographical effects on mesenchymal stem cell morphology and phenotype.
AB  - There is a rapidly growing body of literature on the effects of topography and
      critically, nanotopography on cell adhesion, apoptosis and differentiation.
      Understanding the effects of nanotopography on cell adhesion and morphology and
      the consequences of cell shape changes in the nucleus, and consequently, gene
      expression offers new approaches to the elucidation and potential control of stem
      cell differentiation. In the current study we have used molecular approaches in
      combination with immunohistology and transcript analysis to understand the role
      of nanotopography on mesenchymal stem cell morphology and phenotype. Results
      demonstrate large changes in cell adhesion, nucleus and lamin morphologies in
      response to the different nanotopographies. Furthermore, these changes relate to
      alterations in packing of chromosome territories within the interphase nucleus.
      This, in turn, leads to changes in transcription factor activity and functional
      (phenotypical) signalling including cell metabolism. Nanotopography provides a
      useful, non-invasive tool for studying cellular mechanotransduction, gene and
      protein expression patterns, through effects on cell morphology. The different
      nanotopographies examined, result in different morphological changes in the cyto-
      and nucleo-skeleton. We propose that both indirect (biochemical) and direct
      (mechanical) signalling are important in these early stages of regulating stem
      cell fate as a consequence of altered metabolic changes and altered phenotype.
      The current studies provide new insight on cell-surface interactions and enhance
      our understanding of the modulation of stem cell differentiation with significant
      potential application in regenerative medicine.

PMID- 24123225
TI  - Crystalline hybrid solid materials of palladium and decamethylcucurbit[5]uril as
      recoverable precatalysts for Heck cross-coupling reactions.
AB  - A series of M?Pd?Me10 CB[5] (M=Li, Na, K, Rb, and Cs; Me10
      CB[5]=decamethylcucurbit[5]uril) hybrid solid materials have been successfully
      synthesized for the first time through a simple diffusion method. These as
      prepared hybrid solids have been applied as phosphine-free precatalysts for Heck
      cross-coupling reactions with excellent catalytic performance and good
      recyclability. In the processes of the catalytic reactions, the activated Pd(II)
      species were released from the crystalline hybrid precatalysts and transformed
      into catalytically active Pd nanoparticles, which have been demonstrated as key
      to carry on the catalytic reactions for the recoverable precatalysts M?Pd?Me10
      CB[5] (M=K, Rb, and Cs). It has also been rationalized that the introduction of
      different alkali metals afforded crystalline hybrid precatalysts with different
      crystal structures, which are responsible for their diversified stability and
      reusability presented in Heck reactions. 

PMID- 24123224
TI  - Phase II safety, tolerability, and dose selection study of isradipine as a
      potential disease-modifying intervention in early Parkinson's disease (STEADY
      PD).
AB  - Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be
      neuroprotective in animal models of Parkinson's disease (PD). To establish a
      dosage of isradipine controlled-release (CR) that is tolerable and demonstrates
      preliminary efficacy for use in a future pivotal efficacy trial a Phase 2,
      randomized, double-blind, parallel group trial (Safety, Tolerability and Efficacy
      Assessment of Dynacirc CR in Parkinson Disease [STEADY-PD]) was undertaken in
      subjects with early PD not requiring dopaminergic therapy (dopamine agonists or
      levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching
      placebo daily. The primary outcome was tolerability defined as no more than a 30%
      difference in the proportion of patients completing the study on the originally
      assigned dosage between an active and placebo group. If more than one isradipine
      dosage was tolerable, then a 3-point difference in total Unified Parkinson's
      Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to
      sufficient disability to require dopaminergic therapy) was taken as a criterion
      for selection of the most desirable dosage for future study. STEADY-PD enrolled
      99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26
      patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and
      20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among
      dosages. The most common adverse events were peripheral edema (30) and dizziness
      (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of
      early PD. A large placebo-controlled trial will be necessary and is planned to
      assess efficacy of isradipine 10 mg daily to slow progression of PD disability.

PMID- 24123226
TI  - A comparison of insufficient effort rates, neuropsychological functioning, and
      neuropsychiatric symptom reporting in military veterans and civilians with
      chronic traumatic brain injury.
AB  - Neuropsychological evaluation of persons with chronic traumatic brain injury
      (TBI) symptoms is complicated by multiple factors. The authors explored the
      impact of mechanism of injury, effort testing performance, and neuropsychiatric
      status in a sample of military veterans (V-TBI) and civilians (C-TBI) with
      chronic TBI. V-TBI (n = 74), C-TBI (n = 67), and healthy civilian control (C-HC)
      participants (n = 66), completed a battery of neuropsychological, effort, and
      self-report neuropsychiatric measures. Results indicated that C-HC and C-TBI
      participants exhibited comparably low failure rates on effort tests (6% and 3%,
      respectively). V-TBI participants exhibited significantly higher rates of failure
      (18%). Subgroups (n = 20) of effort-screened participants matched for
      demographics and disability level were compared regarding neuropsychological
      performance and neuropsychiatric self-report. Both TBI groups exhibited limited
      neuropsychological impairment, relative to the C-HC participants. The V-TBI group
      exhibited pronounced neuropsychiatric symptomology compared with the other
      participant groups. The implications of these findings are discussed for
      evaluation in the context of disability and litigation.

PMID- 24123227
TI  - Passive sampling coupled to ultraviolet irradiation: a useful analytical approach
      for studying oxygenated polycyclic aromatic hydrocarbon formation in bioavailable
      mixtures.
AB  - The authors investigated coupling passive sampling technologies with ultraviolet
      irradiation experiments to study polycyclic aromatic hydrocarbon (PAH) and
      oxygenated PAH transformation processes in real-world bioavailable mixtures.
      Passive sampling device (PSD) extracts were obtained from coastal waters impacted
      by the Deepwater Horizon oil spill and Superfund sites in Portland, Oregon, USA.
      Oxygenated PAHs were found in the contaminated waters with our PSDs. All mixtures
      were subsequently exposed to a mild dose of ultraviolet B (UVB). A reduction in
      PAH levels and simultaneous formation of several oxygenated PAHs were measured.
      Site-specific differences were observed with UVB-exposed PSD mixtures.

PMID- 24123228
TI  - A comparison of 12 algorithms for matching on the propensity score.
AB  - Propensity-score matching is increasingly being used to reduce the confounding
      that can occur in observational studies examining the effects of treatments or
      interventions on outcomes. We used Monte Carlo simulations to examine the
      following algorithms for forming matched pairs of treated and untreated subjects:
      optimal matching, greedy nearest neighbor matching without replacement, and
      greedy nearest neighbor matching without replacement within specified caliper
      widths. For each of the latter two algorithms, we examined four different sub
      algorithms defined by the order in which treated subjects were selected for
      matching to an untreated subject: lowest to highest propensity score, highest to
      lowest propensity score, best match first, and random order. We also examined
      matching with replacement. We found that (i) nearest neighbor matching induced
      the same balance in baseline covariates as did optimal matching; (ii) when at
      least some of the covariates were continuous, caliper matching tended to induce
      balance on baseline covariates that was at least as good as the other algorithms;
      (iii) caliper matching tended to result in estimates of treatment effect with
      less bias compared with optimal and nearest neighbor matching; (iv) optimal and
      nearest neighbor matching resulted in estimates of treatment effect with
      negligibly less variability than did caliper matching; (v) caliper matching had
      amongst the best performance when assessed using mean squared error; (vi) the
      order in which treated subjects were selected for matching had at most a modest
      effect on estimation; and (vii) matching with replacement did not have superior
      performance compared with caliper matching without replacement.

PMID- 24123230
TI  - Regio- and stereochemical studies on the nitroso-Diels-Alder reaction with 1,2
      disubstituted dienes.
AB  - The regioselectivity of the nitroso-Diels-Alder reaction between unsymmetrical
      acyclic dienes and Boc-nitroso (Boc=tert-butoxycarbonyl) reagent or the Wightman
      chiral chloronitroso reagents has been studied. With the Boc-nitroso reagent, the
      selectivity is a consequence of steric effects at the C1-position in the diene
      and electronic effects at the C2-position in the diene. The combination of an
      unprotected hydroxyethyl side chain at C1 and an electron-withdrawing group at C2
      allows complete regioselectivity in favour of the proximal isomer. The same
      isomer was obtained exclusively with the chiral nitroso reagent with high
      enantioselectivities. A model based on steric effects is proposed. 

PMID- 24123231
TI  - Donor PNPLA3 rs738409 genotype affects fibrosis progression in liver
      transplantation for hepatitis C.
AB  - The rs738409 G>C single nucleotide polymorphism occurring in the patatin-like
      phospholipase 3 gene has been identified as a novel genetic marker for hepatic
      steatosis. Recent studies also associated rs738409 with fibrosis in hepatitis C
      (HCV). Therefore, we sought to determine the impact of donor and recipient
      rs738409 genotype on the progression of fibrosis after liver transplantation for
      HCV. This cohort study included 101 patients infected with HCV who underwent
      liver transplantation between January 2008, and June 2011. Donor and recipient
      rs738409 genotypes were determined from donor wedge biopsies and recipient
      explants. The time to Ishak stage 3 fibrosis, or HCV-related mortality/graft loss
      was analyzed by the Cox model adjusting for HCV-Donor Risk Index, warm ischemic
      time, pretransplant Model for Endstage Liver Disease (MELD) and viral load. The
      rs738409 CC variant was present in 56% of donors and 57% of recipients. The
      median follow-up period was 620 days. A total of 39 patients developed the
      primary outcome of >=stage 3 fibrosis or HCV-related mortality/graft loss, the
      time to which differed by donor (P = 0.019) but not recipient (P = 0.89)
      genotype. In the multivariate model, donor GC or GG variants had 2.53 times the
      risk (95% confidence interval [CI] 1.25-5.02, P = 0.008) compared to CC variants.
      In the alternative endpoint: stage 3 fibrosis or all-cause mortality/graft loss,
      the effect of donor genotype was attenuated but remained significant at 1.98 (95%
      CI 1.11-3.53). CONCLUSIONS: The rs738409 genotype is an important predictor of
      posttransplant outcome in HCV. Liver, and not adipocytes, is the site at which
      this effect occurs. Our finding may be useful in donor selection for liver
      transplantation with HCV, and may guide decisions regarding early antiviral
      treatment.

PMID- 24123232
TI  - Subjectivity, hygiene, and STI prevention: a normalization paradox in the
      cleanliness practices of female sex workers in post-socialist China.
AB  - This article illuminates the principal mechanisms that increase the risk of STIs
      for female sex workers in China. It draws primarily on my 26 months of
      ethnographic fieldwork (2006-2009) in red-light district neighborhoods in Haikou
      that have become centers of internal migration in post-reform southern China.
      Chinese sex workers here challenge dominant representations of them as illegal,
      immoral, and unclean subordinates and understand themselves also as sacrificing,
      capable, and modern women. I show how the women's conflicted subjectivity,
      continuously shaped through social networks, affects their personal health
      decisions and, significantly, leads them to adopt clinically risky practices. I
      conclude by arguing that public health interventions in southern China in and
      around certain red-light districts should take these conflicted subjectivities
      into account in working to improve sex workers' health. 

PMID- 24123233
TI  - Two-dimensional semi-LASER correlation spectroscopy with well-maintained cross
      peaks.
AB  - PURPOSE: To demonstrate that the limited bandwidth of the second 90 degrees 
      radiofrequency (RF) pulse in two-dimensional (2D) localized correlation
      spectroscopy (L-COSY) induces spatially dependent magnetization transfer that
      results in attenuated cross-peaks, and to propose a new 2D semi-adiabatically
      localized COSY sequence to solve this problem. METHODS AND THEORY: A semi
      localization by adiabatic selective refocusing (semi-LASER or sLASER) method was
      incorporated into the COSY sequence with the slice-selective first 90 degrees  RF
      pulse and the non-slice-selective second 90 degrees  RF pulse to form a new 2D
      sLASER localized COSY sequence, named "sLASER-first-COSY," to solve the problem
      of spatially dependent magnetization transfer. Experiments were performed to
      verify the feasibility and advantages of sLASER-first-COSY sequence over a
      recently reported other sLASER COSY sequence with a slice-selective second 90
      degrees  RF pulse, named "sLASER-last-COSY". RESULTS: Phantom, ex vivo, and in
      vivo human brain experiments demonstrated that sLASER-first-COSY yielded stronger
      cross peaks and higher ratios of cross peak volumes to diagonal peak volumes than
      sLASER-last-COSY. CONCLUSION: As COSY relies on the cross peaks to obtain larger
      dispersion of peaks for quantification, the new sLASER-first-COSY sequence
      yielding well-maintained cross peaks will facilitate more reliable and accurate
      quantification of metabolites with coupled spin systems.

PMID- 24123229
TI  - Quantitative proton MR techniques for measuring fat.
AB  - Accurate, precise and reliable techniques for the quantification of body and
      organ fat distributions are important tools in physiology research. They are
      critically needed in studies of obesity and diseases involving excess fat
      accumulation. Proton MR methods address this need by providing an array of
      relaxometry-based (T1, T2) and chemical shift-based approaches. These techniques
      can generate informative visualizations of regional and whole-body fat
      distributions, yield measurements of fat volumes within specific body depots and
      quantify fat accumulation in abdominal organs and muscles. MR methods are
      commonly used to investigate the role of fat in nutrition and metabolism, to
      measure the efficacy of short- and long-term dietary and exercise interventions,
      to study the implications of fat in organ steatosis and muscular dystrophies and
      to elucidate pathophysiological mechanisms in the context of obesity and its
      comorbidities. The purpose of this review is to provide a summary of mainstream
      MR strategies for fat quantification. The article succinctly describes the
      principles that differentiate water and fat proton signals, summarizes the
      advantages and limitations of various techniques and offers a few illustrative
      examples. The article also highlights recent efforts in the MR of brown adipose
      tissue and concludes by briefly discussing some future research directions.

PMID- 24123234
TI  - The maturation of HIV-1 protease precursor studied by discrete molecular
      dynamics.
AB  - The equilibrium properties of a HIV-1-protease precursor are studied by means of
      an efficient molecular dynamics scheme, which allows for the simulation of the
      folding of the protein monomers and their dimerization into an active form and
      compare them with those of the mature protein. The results of the model provide,
      with atomic detail, an overall account of several experimental findings,
      including the NMR conformation of the mature dimer, the calorimetric properties
      of the system, the effects of the precursor tail on the dimerization constant,
      the secondary chemical shifts of the monomer, and the paramagnetic relaxation
      enhancement data associated with the conformations of the precursor. It is found
      that although the mature protein can dimerize in a unique, single way, the
      precursor populates several dimeric conformations in which monomers are always
      native-like, but their binding can be non-native.

PMID- 24123235
TI  - Specific in situ detection of murine indoleamine 2, 3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase-1 (IDO1) catabolizes the essential amino acid
      tryptophan, acting as a modifier of inflammation and immune tolerance. Recent
      work has implicated IDO1 in many human diseases, including in cancer, chronic
      infection, autoimmune disorders, and neurodegenerative disease, stimulating a
      major surge in preclinical and clinical studies of its pathogenic functions. In
      the mouse, IDO1 is expressed widely but in situ detection of the enzyme in murine
      tissues has been unreliable due to the lack of specific antibodies that do not
      also react with tissues from animals that are genetically deficient in IDO1. Such
      probes are crucial to establish cellular mechanisms since IDO1 appears to act in
      different cell types depending on disease context, but reliable probes have been
      elusive in the field. In this report, we address this issue with the development
      of IDO1 monoclonal antibody 4B7 which specifically recognizes the murine enzyme
      in tissue sections, offering a reliable tool for immunohistology in preclinical
      disease models.

PMID- 24123236
TI  - A general approach for fast detection of charge carrier type and conductivity
      difference in nanoscale materials.
AB  - A general method using a biased atomic force microscopy tip that allows a
      qualitative, fast, and reliable determination of key electronic properties such
      as metallic, n-, or p-doped characteristics has been reported for the first time.
      This method eliminates the detrimental effect of contact in the traditional
      transport measurement and is much simpler than the common-electrostatic force
      microscopy detection method, thus providing a powerful tool for fast
      characterizations of nanomaterials. 

PMID- 24123237
TI  - Disruption of LptA oligomerization and affinity of the LptA-LptC interaction.
AB  - The lipopolysaccharide (LPS)-rich outer membrane (OM) is a unique feature of Gram
      negative bacteria, and LPS transport across the inner membrane (IM) and through
      the periplasm is essential to the biogenesis and maintenance of the OM. LPS is
      transported across the periplasm to the outer leaflet of the OM by the LPS
      transport (Lpt) system, which in Escherichia coli is comprised of seven recently
      identified proteins, including LptA, LptC, LptDE, and LptFGB2 . Structures of the
      periplasmic protein LptA and the soluble portion of the membrane-associated
      protein LptC have been solved and show these two proteins to be highly
      structurally homologous with unique folds. LptA has been shown to form
      concentration dependent oligomers that stack end-to-end. LptA and LptC have been
      shown to associate in vivo and are expected to form a similar protein-protein
      interface to that found in the LptA dimer. In these studies, we disrupted LptA
      oligomerization by introducing two point mutations that removed a lysine and
      glutamine side chain from the C-terminal beta-strand of LptA. This loss of
      oligomerization was characterized using EPR spectroscopy techniques and the
      affinity of the interaction between the mutant LptA protein and WT LptC was
      determined using EPR spectroscopy (Kd = 15 uM) and isothermal titration
      calorimetry (Kd = 14 uM). Kd values were also measured by EPR spectroscopy for
      the interaction between LptC and WT LptA (4 uM) and for WT LptA oligomerization
      (29 uM). These data suggest that the affinity between LptA and LptC is stronger
      than the affinity for LptA oligomerization. 

PMID- 24123238
TI  - 2,4,6-Triarylphosphinines versus 2,4,6-triarylpyridines: an investigation of the
      differences in reactivity between structurally related aromatic phosphorus and
      nitrogen heterocycles.
AB  - The novel atropisomeric pyridine derivative rac-10 has been synthesized and
      structurally characterized. In contrast to its phosphorus analogue 3, axially
      chiral 10 has a considerably lower rotational barrier as estimated by DFT
      calculations. However, the presence of the two enantiomers could be confirmed by
      means of chiral analytical HPLC analysis and by protonation experiments with a
      chiral acid. Compound rac-10 could be further dehydrogenated by treatment with
      DDQ to the benzo(h)quinoline derivative rac-12. This conversion failed for the
      phosphorus analogue rac-3. Interestingly, although 2,4,6-triarylphosphinines
      undergo facile C?H activation with [Cp*IrCl2 ]2 in the presence of NaOAc, this
      reaction does not proceed with the corresponding pyridine derivatives. On the
      other hand, the latter ones can be selectively ortho-metalated with Pd(OAc)2 ,
      leading to acetate-bridged dimeric species, which could be unambiguously
      confirmed by means of X-ray crystal structure analysis. The treatment of
      phosphinines with Pd(OAc)2 led instead to the formation of the unusual cofacial
      oxidative coupling products 16 and 17, which consist of a phosphorus-containing
      cage structure. 

PMID- 24123239
TI  - The adult spinal cord harbors a population of GFAP-positive progenitors with
      limited self-renewal potential.
AB  - Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that
      are intercalated within ependymal cells of the subventricular zone (SVZ). Cells
      showing NSCs characteristics in vitro can also be isolated from the
      periaqueductal region in the adult spinal cord (SC), but contradicting results
      exist concerning their glial versus ependymal identity. We used an inducible
      transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing
      cells in the adult SVZ and SC periaqueduct, and directly and systematically
      compared their self-renewal and multipotential properties in vitro. We
      demonstrate that a population of GFAP(+) cells that share the morphology and the
      antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the
      central canal (CC) throughout the spinal cord. These cells are non-proliferative
      in the intact spinal cord, but incorporate the S-phase marker EdU following
      spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e.,
      deriving from recombined GFAP-expressing cells) were successfully obtained from
      both the intact and injured spinal cord. These spheres however showed limited
      self-renewal properties when compared with SVZ-neurospheres, even after spinal
      cord injury. Altogether, these results demonstrate that significant differences
      exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult
      CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co
      exists alongside with multipotent ependymal cells within the adult SC, we
      identify these cells as multipotent progenitors showing limited self-renewal
      properties.

PMID- 24123240
TI  - Attribution of mild cognitive impairment etiology in patients and their care
      partners.
AB  - OBJECTIVE: This study examined the attribution of mild cognitive impairment (MCI)
      etiology assigned by individuals with MCI and their care partners, and the extent
      to which the dyads agreed on the attribution of MCI etiology. METHODS: We
      conducted secondary analyses of cross-sectional data from a cohort of individuals
      with MCI (n = 60) and their care partners (n = 60). The mean age of the
      individuals with MCI was 71.0 +/- 9.4 years and of care partners 64.2 +/- 11.0
      years. The primary outcome was attribution assigned to memory deficits on the
      Illness Perception Questionnaire. We categorized the attribution of MCI etiology
      as either potentially controllable or uncontrollable factors. We described the
      distribution of MCI etiology with descriptive and contingency tables. We
      determined the odds of a patient or care partner choosing one type of MCI
      etiology over another. RESULTS: Although individuals with MCI and their care
      partners most frequently attributed MCI to uncontrollable factors (81.7% and
      61.0%, respectively), care partners were 28.41 (95% CI, 1.26 to 645.48) times
      more likely to attribute MCI etiology to potentially controllable factors than
      individuals with MCI. No significant associations between demographic factors and
      attribution of MCI etiology were found for the individuals with MCI or the care
      partners. CONCLUSION: Findings demonstrated that members of the dyad attributed
      MCI etiology to different causes. Attributions of MCI etiology should be explored
      by professionals to clarify misconceptions and potentially improve subsequent
      voluntary actions intended to assist oneself or others.

PMID- 24123241
TI  - Dementia in Parkinson's disease: usefulness of the pill questionnaire.
AB  - The Level I algorithm for the diagnosis of dementia associated with Parkinson's
      disease (PD-D) recommended by the Movement Disorder Society task force includes a
      Pill Questionnaire to determine the impact of cognitive decline on daily
      activities. The objective of this study was to test the performance of the Pill
      Questionnaire as a screening tool for the detection of dementia (all-cause) in
      patients with PD and to test the performance of another functional scale
      substituting the Pill Questionnaire for the diagnosis of "probable PD-D" (pPD-D).
      Data were collected from 529 patients who had PD in Hoehn and Yahr stages 1
      through 5. The measures used include the Scales for Outcomes in PD-Motor (SCOPA
      Motor), scales for psychiatric complications, the Mini Mental State Examination,
      the Clinical Impression of Severity Index, and the Pill Questionnaire. The SCOPA
      Motor functional subscale score was categorized as "impact" or "no impact" of PD
      on daily activities. According to clinical judgment, 13.3% of patients had
      dementia. For detecting dementia, the Pill Questionnaire had 89% accuracy,
      although its positive predictive value was 55%. Performance was worse with the
      categorized SCOPA-Motor subscale. According to the Movement Disorder Society task
      force criterion, 85 patients (16.1%) had pPD-D. When the Pill Questionnaire was
      substituted by the categorized SCOPA-Motor subscale, the modified algorithm
      showed sensitivity, specificity, and accuracy indexes over 90% but had positive
      predictive value of 66% for pPD-D diagnosis. Although the Pill Questionnaire
      demonstrated acceptable basic properties as a screening tool for dementia, its
      positive predictive value was low. The SCOPA-Motor subscale cannot be proposed as
      a substitute for the Pill Questionnaire.

PMID- 24123242
TI  - Patient satisfaction with service quality in an oncology setting: implications
      for prognosis in non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the relationship between self-reported satisfaction with
      service quality and overall survival in non-small cell lung cancer (NSCLC).
      DESIGN: A prospective cohort study. SETTING: Cancer Treatment Centers of
      America((r)) from July 2007 and December 2010. PARTICIPANTS: Nine hundred and
      eighty-six returning NSCLC patients. INTERVENTION: Overall patient experience
      'considering everything, how satisfied are you with your overall experience' was
      measured on a 7-point Likert scale ranging from 'completely dissatisfied' to
      'completely satisfied.'. MAIN OUTCOME MEASURE: Patient survival was the primary
      end point. RESULTS: The response rate for this study was 69%. Six hundred
      patients were newly diagnosed, while 386 were previously treated. Four hundred
      sixty-nine were males, while 517 were females. 101, 59, 288 and 538 patients had
      stage I, II, III and IV disease, respectively. Mean age was 58.9 years. Six
      hundred and thirty (63.9%) patients had expired at the time of this analysis.
      Seven hundred and sixty-two (77.3%) patients were 'completely satisfied'. Median
      overall survival was 12.1 months (95% confidence interval (CI): 10.9-13.2
      months). On univariate analysis, 'completely satisfied' patients had a
      significantly lower risk of mortality compared with those not 'completely
      satisfied' [hazard ratio (HR) = 0.70; 95% CI: 0.59-0.84; P < 0.001]. On
      multivariate analysis controlling for stage at diagnosis, prior treatment
      history, age and gender, 'completely satisfied' patients demonstrated
      significantly lower mortality (HR = 0.71; 95% CI: 0.60-0.85; P < 0.001) compared
      with those not 'completely satisfied'. CONCLUSIONS: Self-reported experience with
      service quality was an independent predictor of survival in NSCLC patients
      undergoing oncologic treatment, a novel finding in the literature. Based on these
      provocative findings, further exploration of this relationship is warranted in
      well-designed prospective studies.

PMID- 24123243
TI  - High-quality chronic care delivery improves experiences of chronically ill
      patients receiving care.
AB  - OBJECTIVE: Investigate whether high-quality chronic care delivery improved the
      experiences of patients. DESIGN: This study had a longitudinal design. SETTING
      AND PARTICIPANTS: We surveyed professionals and patients in 17 disease management
      programs targeting patients with cardiovascular diseases, chronic obstructive
      pulmonary disease, heart failure, stroke, comorbidity and eating disorders. MAIN
      OUTCOME MEASURES: Patients completed questionnaires including the Patient
      Assessment of Chronic Illness Care (PACIC) [T1 (2010), 2637/4576 (58%); T2
      (2011), 2314/4330 (53%)]. Professionals' Assessment of Chronic Illness Care
      (ACIC) scores [T1, 150/274 (55%); T2, 225/325 (68%)] were used as a context
      variable for care delivery. We used two-tailed, paired t-tests to investigate
      improvements in chronic illness care quality and patients' experiences with
      chronic care delivery. We employed multilevel analyses to investigate the
      predictive role of chronic care delivery quality in improving patients'
      experiences with care delivery. RESULTS: Overall, care quality and patients'
      experiences with chronic illness care delivery significantly improved. PACIC
      scores improved significantly from 2.89 at T1 to 2.96 at T2 and ACIC-S scores
      improved significantly from 6.83 at T1 to 7.18 at T2. After adjusting for
      patients' experiences with care delivery at T1, age, educational level, marital
      status, gender and mental and physical quality of life, analyses showed that the
      quality of chronic care delivery at T1 (P < 0.001) and changes in care delivery
      quality (P < 0.001) predicted patients' experiences with chronic care delivery at
      T2. CONCLUSION: This research showed that care quality and changes therein
      predict more positive experiences of patients with various chronic conditions
      over time.

PMID- 24123244
TI  - Improved relapse-free survival after autologous stem cell transplantation does
      not translate into better quality of life in chronic lymphocytic leukemia:
      lessons from the randomized European Society for Blood and Marrow Transplantation
      Intergroup study.
AB  - In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical
      studies with relapse-free survival (RFS) as the primary endpoint. The randomized
      EBMT-Intergroup trial compared high-dose therapy and autologous stem cell
      transplantation (ASCT) to observation and demonstrated a substantial improvement
      of RFS without showing improved overall survival for the transplant arm. Here we
      report quality of life (QoL) information of the first 3 years following
      randomization from that study. The main objective was to assess the impact of
      treatment on QoL over time. Two secondary analyses were performed to further
      investigate the impact of ASCT and relapse on QoL. In the primary analysis, we
      demonstrate an adverse impact of ASCT on QoL which was largest at 4 months and
      continued throughout the first year after randomization. Further, we demonstrated
      a sustained adverse impact of relapse on QoL which worsened over time. Despite
      better disease control by ASCT the side effects thus turned the net effect
      towards inferior QoL in the first year and comparable QoL in the following 2
      years after randomization. This study emphasizes the importance of information
      concerning QoL impacts when patients are counseled about treatments aimed at
      improving RFS in the absence of a survival benefit.

PMID- 24123245
TI  - The neuroethics and neurolaw of brain injury.
AB  - Neuroethics and neurolaw are fields of study that involve the interface of
      neuroscience with clinical and legal decision-making. The past two decades have
      seen increasing attention being paid to both fields, in large part because of the
      advances in neuroimaging techniques and improved ability to visualize and measure
      brain structure and function. Traumatic brain injury (TBI), along with its acute
      and chronic sequelae, has emerged as a focus of neuroethical issues, such as
      informed consent for treatment and research, diagnostic and prognostic
      uncertainties, and the subjectivity of interpretation of data. The law has also
      more frequently considered TBI in criminal settings for exculpation, mitigation
      and sentencing purposes and in tort and administrative law for personal injury,
      disability and worker's compensation cases. This article provides an overview of
      these topics with an emphasis on the current challenges that the neuroscience of
      TBI faces in the medicolegal arena.

PMID- 24123246
TI  - Upregulation of GLT-1 by treatment with ceftriaxone alleviates radicular pain by
      reducing spinal astrocyte activation and neuronal hyperexcitability.
AB  - Cervical nerve root injury commonly leads to radicular pain. Normal sensation
      relies on regulation of extracellular glutamate in the spinal cord by glutamate
      transporters. The goal of this study was to define the temporal response of
      spinal glutamate transporters (glial glutamate transporter 1 [GLT-1], glutamate
      aspartate transporter [GLAST], and excitatory amino acid carrier 1) following
      nerve root compressions that do or do not produce sensitivity in the rat and to
      evaluate the role of glutamate uptake in radicular pain by using ceftriaxone to
      upregulate GLT-1. Compression was applied to the C7 nerve root. Spinal glutamate
      transporter expression was evaluated at days 1 and 7. In a separate study, rats
      underwent a painful root compression and were treated with ceftriaxone or the
      vehicle saline. Glial glutamate transporter expression, astrocytic activation
      (glial fibrillary acidic protein [GFAP]), and neuronal excitability were assessed
      at day 7. Both studies measured behavioral sensitivity for 7 days after injury.
      Spinal GLT-1 significantly decreased (P < 0.04) and spinal GLAST significantly
      increased (P = 0.036) at day 7 after a root injury that also produced sensitivity
      to both mechanical and thermal stimuli. Within 1 day after ceftriaxone treatment
      (day 2), mechanical allodynia began to decrease; both mechanical allodynia and
      thermal hyperalgesia were attenuated (P < 0.006) by day 7. Ceftriaxone also
      reduced (P < 0.024) spinal GFAP and GLAST expression, and neuronal
      hyperexcitability in the spinal dorsal horn, restoring the proportion of spinal
      neurons classified as wide dynamic range to that of normal. These findings
      suggest that nerve root-mediated pain is maintained jointly by spinal astrocytic
      reactivity and neuronal hyperexcitability and that these spinal modifications are
      associated with reduced glutamate uptake by GLT-1.

PMID- 24123247
TI  - Serum bile acids in intrahepatic cholestasis of pregnancy: not just a diagnostic
      test.

PMID- 24123248
TI  - FOUR LIPS and MYB88 conditionally restrict the G1/S transition during stomatal
      formation.
AB  - Consistent with their valve-like function in shoot-atmosphere gas exchange, guard
      cells are smaller than other epidermal cells and usually harbour 2C DNA levels in
      diploid plants. The paralogous Arabidopsis R2R3 MYB transcription factors, FOUR
      LIPS and MYB88, ensure that stomata contain just two guard cells by restricting
      mitosis. The loss of both FLP and MYB88 function in flp myb88 double mutants
      induces repeated mitotic divisions that lead to the formation of clusters of
      stomata in direct contact. By contrast, CYCLIN DEPENDENT KINASE B1 function is
      required for the symmetric division that precedes stomatal maturation. It was
      found that blocking mitosis by chemically disrupting microtubules or by the
      combined loss of FLP/MYB88 and CDKB1 function, causes single (undivided) guard
      cells (sGCs) to enlarge and attain mean DNA levels of up to 10C. The loss of both
      FLP and CDKB1 function also dramatically increased plastid number, led to the
      formation of multiple nuclei in GCs, altered GC and stomatal shape, and disrupted
      the fate of lineage-specific stem cells. Thus, in addition to respectively
      restricting and promoting symmetric divisions, FLP and CDKB1 together also
      conditionally restrict the G1/S transition and chloroplast and nuclear number,
      and normally maintain fate and developmental progression throughout the stomatal
      cell lineage. 

PMID- 24123249
TI  - Flooding of the apoplast is a key factor in the development of hyperhydricity.
AB  - The physiological disorder hyperhydricity occurs frequently in tissue culture and
      causes several morphological abnormalities such as thick, brittle, curled, and
      translucent leaves. It is well known that hyperhydric shoots are characterized by
      a high water content, but how this is related to the abnormalities is not clear.
      It was observed that water accumulated extensively in the apoplast of leaves of
      hyperhydric Arabidopsis seedlings and flooded apoplastic air spaces almost
      completely. In hyperhydric Arabidopsis seedlings, the volume of apoplastic air
      was reduced from 85% of the apoplast to only 15%. Similar results were obtained
      with hyperhydric shoots of statice. The elevated expression of hypoxia-responsive
      genes in hyperhydric seedlings showed that the water saturation of the apoplast
      decreased oxygen supply. This demonstrates a reduced gas exchange between the
      symplast and its surroundings, which will consequently lead to the accumulation
      of gases in the symplast, for example ethylene and methyl jasmonate. The
      impairment of gas exchange probably brings about the symptoms of hyperhydricity.
      Interestingly, stomatal aperture was reduced in hyperhydric plants, a previously
      reported response to injection of water into the apoplast. Closure of the stomata
      and the accumulation of water in the apoplast may be the reasons why seedlings
      with a low level of hyperhydricity showed improved acclimatization after planting
      into soil. 

PMID- 24123250
TI  - A biophysical model of kiwifruit (Actinidia deliciosa) berry development.
AB  - A model of kiwifruit berry development is presented, building on the model of
      Fishman and Genard used for peach fruit. That model has been extended to
      incorporate a number of important features of kiwifruit growth. First, the
      kiwifruit berry is attached to the stem through a pedicel/receptacle complex
      which contributes significantly to the hydraulic resistance between the stem and
      the fruit, and this resistance changes considerably during the season. Second,
      much of the carbohydrate in kiwifruit berries is stored as starch until the fruit
      matures late in the season, when the starch hydrolyses to soluble sugars. This
      starch storage has a major effect on the osmotic potential of the fruit, so an
      existing model of kiwifruit starch dynamics was included in the model. Using
      previously published approaches, we also included elasticity and extended the
      modelling period to cover both the cell division and cell expansion phases of
      growth. The resulting model showed close simulation of field observations of
      fresh weight, dry matter, starch, and soluble solids in kiwifruit. Comparison
      with continuous measurements of fruit diameter confirmed that elasticity was
      needed to adequately simulate observed diurnal variation in fruit size.
      Sensitivity analyses suggested that the model is particularly sensitive to
      variation in inputs relating to water (stem water potential and the humidity of
      the air), and to parameters controlling cell expansion (cell wall extensibility).
      Some limitations in the model structure were identified, suggesting that a
      revised model including current apoplastic/symplastic concepts needs to be
      developed. 

PMID- 24123251
TI  - Proteomic and phosphoproteomic analysis of polyethylene glycol-induced osmotic
      stress in root tips of common bean (Phaseolus vulgaris L.).
AB  - Previous studies have shown that polyethylene glycol (PEG)-induced osmotic stress
      (OS) reduces cell-wall (CW) porosity and limits aluminium (Al) uptake by root
      tips of common bean (Phaseolus vulgaris L.). A subsequent transcriptomic study
      suggested that genes related to CW processes are involved in adjustment to OS. In
      this study, a proteomic and phosphoproteomic approach was applied to identify OS
      induced protein regulation to further improve our understanding of how OS affects
      Al accumulation. Analysis of total soluble proteins in root tips indicated that,
      in total, 22 proteins were differentially regulated by OS; these proteins were
      functionally categorized. Seventy-seven per- cent of the total expressed proteins
      were involved in metabolic pathways, particularly of carbohydrate and amino acid
      metabolism. An analysis of the apoplastic proteome revealed that OS reduced the
      level of five proteins and increased that of seven proteins. Investigation of the
      total soluble phosphoproteome suggested that dehydrin responded to OS with an
      enhanced phosphorylation state without a change in abundance. A cellular
      immunolocalization analysis indicated that dehydrin was localized mainly in the
      CW. This suggests that dehydrin may play a major protective role in the OS
      induced physical breakdown of the CW structure and thus maintenance of the
      reversibility of CW extensibility during recovery from OS. The proteomic and
      phosphoproteomic analyses provided novel insights into the complex mechanisms of
      OS-induced reduction of Al accumulation in the root tips of common bean and
      highlight a key role for modification of CW structure. 

PMID- 24123252
TI  - Differentially expressed myo-inositol monophosphatase gene (CaIMP) in chickpea
      (Cicer arietinum L.) encodes a lithium-sensitive phosphatase enzyme with broad
      substrate specificity and improves seed germination and seedling growth under
      abiotic stresses.
AB  - myo-Inositol monophosphatase (IMP) is an essential enzyme in the myo-inositol
      metabolic pathway where it primarily dephosphorylates myo-inositol 1-phosphate to
      maintain the cellular inositol pool which is important for many metabolic and
      signalling pathways in plants. The stress-induced increased accumulation of
      inositol has been reported in a few plants including chickpea; however, the role
      and regulation of IMP is not well defined in response to stress. In this work, it
      has been shown that IMP activity is distributed in all organs in chickpea and was
      noticeably enhanced during environmental stresses. Subsequently, using degenerate
      oligonucleotides and RACE strategy, a full-length IMP cDNA (CaIMP) was cloned and
      sequenced. Biochemical study revealed that CaIMP encodes a lithium-sensitive
      phosphatase enzyme with broad substrate specificity, although maximum activity
      was observed with the myo-inositol 1-phosphate and l-galactose 1-phosphate
      substrates. Transcript analysis revealed that CaIMP is differentially expressed
      and regulated in different organs, stresses and phytohormones. Complementation
      analysis in Arabidopsis further confirmed the role of CaIMP in l-galactose 1
      phosphate and myo-inositol 1-phosphate hydrolysis and its participation in myo
      inositol and ascorbate biosynthesis. Moreover, Arabidopsis transgenic plants over
      expressing CaIMP exhibited improved tolerance to stress during seed germination
      and seedling growth, while the VTC4/IMP loss-of-function mutants exhibited
      sensitivity to stress. Collectively, CaIMP links various metabolic pathways and
      plays an important role in improving seed germination and seedling growth,
      particularly under stressful environments. 

PMID- 24123254
TI  - Difunctionalized {closo-1-CB11 } clusters: 1- and 2-amino-12-ethynylcarba-closo
      dodecaborates.
AB  - Carba-closo-dodecaborate anions with two functional groups have been synthesized
      via a simple two-step procedure starting from monoamino-functionalized {closo-1
      CB11 } clusters. Iodination at the antipodal boron atom provided access to [1-H2
      N-12-I-closo-1-CB11 H10 ](-) (1 a) and [2-H2 N-12-I-closo-1-CB11 H10 ](-) (2 a),
      which have been transformed into the anions [1-H2 N-12-RC?C-closo-1-CB11 H10 ](-)
      (R=H (1 b), Ph (1 c), Et3 Si (1 d)) and [2-H2 N-12-RC?C-closo-1-CB11 H10 ](-)
      (R=H (2 b), Ph (2 c), Et3 Si (2 d)) by microwave-assisted Kumada-type cross
      coupling reactions. The syntheses of the inner salts 1-Me3 N-12-RC?C-closo-1-CB11
      H10 (R=H (1 e), Et3 Si (1 f)) and 2-Me3 N-12-RC?C-closo-1-CB11 H10 (R=H (2 e),
      Et3 Si (2 f)) are the first examples for a further derivatization of the new
      anions. All {closo-1-CB11 } clusters have been characterized by multinuclear NMR
      and vibrational spectroscopy as well as by mass spectrometry. The crystal
      structures of Cs1 a, [Et4 N]2 a, K1 b, [Et4 N]1 c, [Et4 N]2 c, 1 e, and [Et4 N][1
      H2 N-2-F-12-I-closo-1-CB11 H9 ]?0.5 H2 O ([Et4 N]4 a?0.5 H2 O) have been
      determined. Experimental spectroscopic data and especially spectroscopic data and
      bond properties derived from DFT calculations provide some information on the
      importance of inductive and resonance-type effects for the transfer of electronic
      effects through the {closo-1-CB11 } cage. 

PMID- 24123253
TI  - Cerebral blood flow response to acute hypoxic hypoxia.
AB  - Hypoxic hypoxia (inspiratory hypoxia) stimulates an increase in cerebral blood
      flow (CBF) maintaining oxygen delivery to the brain. However, this response,
      particularly at the tissue level, is not well characterised. This study
      quantifies the CBF response to acute hypoxic hypoxia in healthy subjects. A 20
      min hypoxic (mean P(ETO2) = 52 mmHg) challenge was induced and controlled by
      dynamic end-tidal forcing whilst CBF was measured using pulsed arterial spin
      labelling perfusion MRI. The rate constant, temporal delay and magnitude of the
      CBF response were characterised using an exponential model for whole-brain and
      regional grey matter. Grey matter CBF increased from 76.1 mL/100 g/min (95%
      confidence interval (CI) of fitting: 75.5 mL/100 g/min, 76.7 mL/100 g/min) to
      87.8 mL/100 g/min (95% CI: 86.7 mL/100 g/min, 89.6 mL/100 g/min) during hypoxia,
      and the temporal delay and rate constant for the response to hypoxia were 185 s
      (95% CI: 132 s, 230 s) and 0.0035 s(-1) (95% CI: 0.0019 s(-1), 0.0046 s(-1)),
      respectively. Recovery from hypoxia was faster with a delay of 20 s (95% CI: -38
      s, 38 s) and a rate constant of 0.0069 s(-1) (95% CI: 0.0020 s(-1), 0.0103 s(
      1)). R2*, an index of blood oxygenation obtained simultaneously with the CBF
      measurement, increased from 30.33 s(-1) (CI: 30.31 s(-1), 30.34 s(-1)) to 31.48
      s(-1) (CI: 31.47 s(-1), 31.49 s(-1)) with hypoxia. The delay and rate constant
      for changes in R2 * were 24 s (95% CI: 21 s, 26 s) and 0.0392 s(-1) (95% CI:
      0.0333 s(-1), 0.045 s(-1)), respectively, for the hypoxic response, and 12 s (95%
      CI: 10 s, 13 s) and 0.0921 s(-1) (95% CI: 0.0744 s(-1), 0.1098 s(-1)/) during the
      return to normoxia, confirming rapid changes in blood oxygenation with the end
      tidal forcing system. CBF and R2* reactivity to hypoxia differed between
      subjects, but only R2* reactivity to hypoxia differed significantly between brain
      regions.

PMID- 24123255
TI  - Rapid acquisition of 14N solid-state NMR spectra with broadband cross
      polarization.
AB  - Nitrogen is an element of utmost importance in chemistry, biology and materials
      science. Of its two NMR-active isotopes, (14)N and (15)N, solid-state NMR (SSNMR)
      experiments are rarely conducted upon the former, due to its low gyromagnetic
      ratio (gamma) and broad powder patterns arising from first-order quadrupolar
      interactions. In this work, we propose a methodology for the rapid acquisition of
      high quality (14)N SSNMR spectra that is easy to implement, and can be used for a
      variety of nitrogen-containing systems. We demonstrate that it is possible to
      dramatically enhance (14)N NMR signals in spectra of stationary, polycrystalline
      samples (i.e., amino acids and active pharmaceutical ingredients) by means of
      broadband cross polarization (CP) from abundant nuclei (e.g., (1)H). The
      BRoadband Adiabatic INversion Cross-Polarization (BRAIN-CP) pulse sequence is
      combined with other elements for efficient acquisition of ultra-wideline SSNMR
      spectra, including Wideband Uniform-Rate Smooth-Truncation (WURST) pulses for
      broadband refocusing, Carr-Purcell Meiboom-Gill (CPMG) echo trains for T2-driven
      S/N enhancement, and frequency-stepped acquisitions. The feasibility of utilizing
      the BRAIN-CP/WURST-CPMG sequence is tested for (14)N, with special consideration
      given to (i) spin-locking integer spin nuclei and maintaining adiabatic
      polarization transfer, and (ii) the effects of broadband polarization transfer on
      the overlapping satellite transition patterns. The BRAIN-CP experiments are shown
      to provide increases in signal-to-noise ranging from four to ten times and
      reductions of experimental times from one to two orders of magnitude compared to
      analogous experiments where (14)N nuclei are directly excited. Furthermore,
      patterns acquired with this method are generally more uniform than those acquired
      with direct excitation methods. We also discuss the proposed method and its
      potential for probing a variety of chemically distinct nitrogen environments.

PMID- 24123256
TI  - Prediction and validation of the unexplored RNA-binding protein atlas of the
      human proteome.
AB  - Detecting protein-RNA interactions is challenging both experimentally and
      computationally because RNAs are large in number, diverse in cellular location
      and function, and flexible in structure. As a result, many RNA-binding proteins
      (RBPs) remain to be identified. Here, a template-based, function-prediction
      technique SPOT-Seq for RBPs is applied to human proteome and its result is
      validated by a recent proteomic experimental discovery of 860 mRNA-binding
      proteins (mRBPs). The coverage (or sensitivity) is 42.6% for 1217 known RBPs
      annotated in the Gene Ontology and 43.6% for 860 newly discovered human mRBPs.
      Consistent sensitivity indicates the robust performance of SPOT-Seq for
      predicting RBPs. More importantly, SPOT-Seq detects 2418 novel RBPs in human
      proteome, 291 of which were validated by the newly discovered mRBP set. Among 291
      validated novel RBPs, 61 are not homologous to any known RBPs. Successful
      validation of predicted novel RBPs permits us to further analysis of their
      phenotypic roles in disease pathways. The dataset of 2418 predicted novel RBPs
      along with confidence levels and complex structures is available at http://sparks
      lab.org (in publications) for experimental confirmations and hypothesis
      generation.

PMID- 24123257
TI  - Quantitative (23) Na MRI of human knee cartilage using dual-tuned (1) H/(23) Na
      transceiver array radiofrequency coil at 7 tesla.
AB  - PURPOSE: To develop quantitative dual-tuned (DT) (1) H/(23) Na MRI of human knee
      cartilage in vivo at 7 Tesla (T). MATERIALS AND METHODS: A sensitive (23) Na
      transceiver array RF coil was developed at 7T. B1 fields generated by the
      transceiver array coil were characterized and corrected in the (23) Na images.
      Point spread function (PSF) of the (23) Na images was measured, and the signal
      decrease due to partial-volume-effect was compensated in [(23) Na] quantification
      of knee cartilage. SNR and [(23) Na] in anterior femoral cartilage were measured
      from seven healthy subjects. RESULTS: SNR of (23) Na image with the transceiver
      array coil was higher than that of birdcage coil. SNR in the cartilage at 2-mm
      isotropic resolution was 26.80 +/- 3.69 (n = 7). B1 transmission and reception
      fields produced by the DT coil at 7T were similar to each other. Effective full
      width-half-maximum of (23) Na image was ~5 mm at 2-mm resolution. Mean [(23) Na]
      was 288.13 +/- 29.50 mM (n = 7) in the anterior femoral cartilage of normal
      subjects. CONCLUSION: We developed a new high-sensitivity (23) Na RF coil for
      knee MRI at 7T. Our (1) H/(23) Na MRI allowed quantitative measurement of [(23)
      Na] in knee cartilage by measuring PSF and cartilage thickness from (23) Na and
      (1) H image, respectively.

PMID- 24123258
TI  - Organic electrochemical transistors with maximum transconductance at zero gate
      bias.
AB  - By varying device geometry we have engineered organic electrochemical transistors
      that exhibit their maximum transconductance at zero gate bias. This enables the
      design of a simplified amplifying transducer, allowing for improved integration
      with biomedical systems where prolonged gate bias can be detrimental. 

PMID- 24123259
TI  - Frontline activists: Mexicana care workers, subjectivity, and the defense of the
      elderly.
AB  - In this article, I focus on Mexican immigrant women who, as care workers in
      various care settings in the wealthy city of Santa Barbara, California, attempt
      to defend aging Americans patients from devaluation and harm. To understand why
      vulnerable women defend more privileged citizens of the nation, I address
      Mexicana subjectivity. I argue that neoliberal policies have created multiple
      vulnerabilities for Mexican women and it is in formal care contexts where these
      vulnerabilities intertwine with that of their patients. Workers' feelings of
      shame, complicity, and empathy help explain a defense of the Other. A significant
      form of defense is informal sector family-based care. This article is based on
      ethnographic fieldwork conducted between 2009 and 2011. 

PMID- 24123260
TI  - Effect of gold nanoparticles and ciprofloxacin on microbial catabolism: a
      community-based approach.
AB  - The effect of gold nanoparticles (AuNPs) and ciprofloxacin on the catabolism of
      microbial communities was assessed. This was accomplished through an ex situ
      methodology designed to give a priori knowledge on the potential for
      nanoparticles, or other emerging contaminants, to affect the catabolic
      capabilities of microbial communities in the environment. Microbial communities
      from a variety of sources were incubated with 31 prespecified carbon sources and
      either National Institute of Standards and Technology reference material 10-nm
      AuNPs or ciprofloxacin on 96-well microtiter plates. From the ciprofloxacin
      study, dose-response curves were generated and exemplified how this method can be
      used to assess the effect of a toxicant on overall catabolic capabilities of
      microbial communities. With 10-nm AuNPs at concentrations ranging from 0.01 ug/mL
      to 0.5 ug/mL, rhizosphere communities from Typha roots were only slightly
      catabolically inhibited at a single concentration (0.05 ug/mL); no effects were
      seen on wetland water communities, and a minor positive (i.e., enhanced catabolic
      capabilities) effect was observed for loamy soil communities. This positive
      effect might have been because of a thin layer of citrate found on these AuNPs
      that initiated cometabolism with some of the carbon sources studied. Under the
      conditions considered, the possible adverse effects of AuNPs on the catabolic
      capabilities of microbial communities appears to be minimal.

PMID- 24123261
TI  - Cardiac R2* values are independent of the image analysis approach employed.
AB  - PURPOSE: To determine whether systematic differences were present between
      myocardial R2* values obtained with two different decay models: truncation and
      exponential + constant (Exp-C). METHODS: Single-center cohorts were used to
      compare black and bright blood sequences separately, and a multicenter cohort of
      mixed bright and black blood studies was used to assess the generalizability.
      Truncated exponential estimates were calculated with CMRtools, which uses a
      single region of interest (ROI) method. Exp-C estimates were calculated using a
      pixelwise approach. RESULTS: No differences could be distinguished based upon
      whether a white or black blood sequence was examined. The two fitting algorithms
      yielded similar R2* values, with R-squared values exceeding 0.997 and a
      coefficient of variation of 3% to 4%. Results using the pixelwise method yielded
      a small systematic bias (~3%) that became apparent in patients with severe iron
      deposition. This disparity disappeared when Exp-C fitting was used on a single
      ROI, suggesting that the use of pixelwise mapping was responsible for the bias.
      In the multicenter cohort, the strong agreement between the two fitting
      approaches was reconfirmed. CONCLUSION: Cardiac R2* values are independent of the
      signal model used for its calculation over clinically relevant ranges. Clinicians
      can compare results among centers using these disparate approaches with
      confidence.

PMID- 24123262
TI  - Presenting concerns of veterans entering treatment for posttraumatic stress
      disorder.
AB  - Patient-centered care involves engaging patients as partners in establishing
      treatment priorities. No prior studies have examined what specific problems
      veterans hope to address when they enter posttraumatic stress disorder (PTSD)
      treatment. Veterans starting outpatient (n = 216) and residential (n = 812) PTSD
      treatment in 2 multisite care management trials specified (open-ended) the 2 or 3
      problems that they most wanted to improve through treatment. Over 80% mentioned
      PTSD-symptom-related concerns including PTSD or trauma (19.2% to 19.9% of
      patients), anger (31.0% to 36.7%), sleep problems (14.3% to 27.3%), nightmares
      (12.3% to 19.4%), and estrangement/isolation (7.9% to 20.8%). Other common
      problems involved depression (23.1% to 36.5%), anxiety not specific to PTSD
      (23.9% to 27.8%), relationships (20.4% to 24.5%), and improving coping or
      functioning (19.2% to 20.4%). Veterans' treatment goals varied significantly by
      outpatient versus residential setting, gender, and period of military service.
      Our findings confirm the importance of educating patients about how available
      efficacious treatments relate to clients' personal goals. Our results also
      suggest that clinicians should be prepared to offer interventions or provide
      referrals for common problems such as anger, nightmares, sleep, depression, or
      relationship difficulties if these problems do not remit with trauma-focused
      psychotherapy or if patients are unwilling to undergo trauma-focused treatment. 

PMID- 24123263
TI  - Nuclear structures surrounding internal lamin invaginations.
AB  - A- and C-type lamins are intermediate filament proteins responsible for the
      maintenance of nuclear shape and most likely nuclear architecture. Here, we
      propose that pronounced invaginations of A/C-type lamins into the nuclear
      interior represent channels for the transport of regulatory molecules to and from
      nuclear and nucleolar regions. Using fluorescent protein technology and
      immunofluorescence, we show that A-type lamin channels interact with several
      nuclear components, including fibrillarin- and UBF-positive regions of nucleoli,
      foci of heterochromatin protein 1 beta, polycomb group bodies, and genomic
      regions associated with DNA repair. Similar associations were observed between
      A/C-type lamin channels and nuclear pores, lamin-associated protein LAP2alpha,
      and promyelocytic leukemia nuclear bodies. Interestingly, regions with high
      levels of A/C-type lamins had low levels of B-type lamins, and vice versa. These
      characteristics were observed in primary and immortalized mouse embryonic
      fibroblasts as well as human and mouse embryonic stem cell colonies exhibiting
      stem cell-specific lamin positivity. Our findings indicate that internal channels
      formed by nuclear lamins likely contribute to normal cellular processes through
      association with various nuclear and nucleolar structures.

PMID- 24123264
TI  - Vaulted biaryls in catalysis: A structure-activity relationship guided tour of
      the immanent domain of the VANOL ligand.
AB  - The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate)
      that is assembled in situ from three equivalents of B(OPh)3 and one of the VANOL
      ligand by a molecule of substrate. The substrates are bound to the boroxinate by
      H bonds to oxygen atoms O1-O3. The effects of introducing substituents at each
      position of the naphthalene core of the VANOL ligand are systematically
      investigated in an aziridination reaction. Substituents in the 4,4'- and 8,8'
      positions have a negative effect on catalyst performance, whereas, substituents
      in the 7- and 7'-positions have the biggest impact in a positive direction. 

PMID- 24123265
TI  - Small proline rich protein 2a in benign and malignant liver disease.
AB  - STAT3-driven expression of small proline rich protein 2a (SPRR2a), which acts as
      an src homology 3 (SH3) domain ligand, induces biliary epithelial cell (BEC)
      epithelial-mesenchymal transition (EMT), which, in turn, promotes wound healing.
      SPRR2a also quenches free radicals and protects against oxidative stress and DNA
      damage in nonneoplastic BEC. Sprr2a-induced EMT also increases local invasiveness
      of cholangiocarcinomas (CC), but prevents metastases. Understanding SPRR2a
      regulation of EMT has potential for therapeutic targeting in both benign and
      malignant liver disease. Molecular mechanisms responsible for SPRR2a-induced EMT
      were characterized, in vitro, and then evidence for utilization of these pathways
      was sought in human intrahepatic CC, in vivo, using multiplex labeling and
      software-assisted morphometric analysis. SPRR2a complexes with ZEB1 and CtBP on
      the microRNA (miR)-200c/141 promoter resulting in synergic suppression of miR
      200c/141 transcription, which is required for maintenance of the BEC epithelial
      phenotype. SPRR2a induction promotes dephosphorylation and nuclear translocation
      of the SH3-domain containing protein GRB2 and an SH3-domain ligand in ZEB1 is
      required for SPRR2a-induced synergic suppression of miR-200c/141. Multiplex
      protein labeling of CC and morphometric analyses showed: 1) up-regulation of ZEB
      1, and 2) down-regulation of CK19 in intrahepatic CC compared to nonneoplastic
      BEC, consistent with previous CC proteomic studies showing EMT during
      cholangiocarcinogenesis. CONCLUSION: SPRR2a modulates ZEB-1 signaling by way of
      miR-200c/141-associated EMT through SH3-domain networks and contributes to benign
      and malignant BEC wound-healing responses.

PMID- 24123266
TI  - Vascular depression: overrepresented among African Americans?
AB  - OBJECTIVE: Our primary aim was to compare the rate of vascular depression among a
      clinical sample of African American and Caucasian depressed older adults.
      Secondary aims included characterizing the clinical and neuropsychological
      profile of vascular depression and comparing antidepressant response rates
      between patients with vascular and nonvascular depression. METHODS: This was a
      two-site, multi-ethnic, open 8-week trial of antidepressant medication in older
      adults with depression. Men and women 50 years or older meeting DSM-IV criteria
      for nonpsychotic unipolar depression participated in this trial. Each participant
      underwent a comprehensive psychiatric and neuropsychological evaluation and a
      brain MRI, which were performed at baseline. RESULTS: Forty-six patients met
      inclusion and exclusion criteria. Forty-two of those patients received an MRI at
      baseline. Sixteen patients met criteria for vascular depression. Patients with
      vascular depression were significantly more likely to be African American and
      have a higher likelihood of being female, a higher rate of hypertension and
      psychomotor retardation, a lower rate of family history of affective illness, and
      frontal systems dysfunction on neuropsychological testing. The difference in
      response rates between patients with vascular and nonvascular depression did not
      reach statistical significance. CONCLUSIONS: This is the first study to document
      high rates of vascular depression in a clinical sample of African Americans and
      Caucasians. Our findings suggest that vascular depression may be overrepresented
      among African Americans, which is consistent with the high rates of
      cardiovascular disease, hypertension, and stroke in this population.

PMID- 24123267
TI  - Defining optimal cutoff scores for cognitive impairment using Movement Disorder
      Society Task Force criteria for mild cognitive impairment in Parkinson's disease.
AB  - The recently proposed Movement Disorder Society (MDS) Task Force diagnostic
      criteria for mild cognitive impairment in Parkinson's disease (PD-MCI) represent
      a first step toward a uniform definition of PD-MCI across multiple clinical and
      research settings. However, several questions regarding specific criteria remain
      unanswered, including optimal cutoff scores by which to define impairment on
      neuropsychological tests. Seventy-six non-demented PD patients underwent
      comprehensive neuropsychological assessment and were classified as PD-MCI or PD
      with normal cognition (PD-NC). The concordance of PD-MCI diagnosis by MDS Task
      Force Level II criteria (comprehensive assessment), using a range of standard
      deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD-MCI
      or PD-NC. Sensitivity, specificity, and positive and negative predictive values
      were examined for each cutoff score. PD-MCI subtype classification and
      distribution of cognitive domains impaired were evaluated. Concordance for PD-MCI
      diagnosis was greatest for defining impairment on neuropsychological tests using
      a 2 SD cutoff score below appropriate norms. This cutoff also provided the best
      discriminatory properties for separating PD-MCI from PD-NC compared with other
      cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more
      frequent than single domain impairment, with predominant executive function,
      memory, and visuospatial function deficits. Application of the MDS Task Force PD
      MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at
      a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI
      with the Level II criteria suggests not only influences of testing abnormality
      requirements, but also the widespread nature of cognitive deficits within PD-MCI.

PMID- 24123268
TI  - Contributions of Aspergillus fumigatus ATP-binding cassette transporter proteins
      to drug resistance and virulence.
AB  - In yeast cells such as those of Saccharomyces cerevisiae, expression of ATP
      binding cassette (ABC) transporter proteins has been found to be increased and
      correlates with a concomitant elevation in azole drug resistance. In this study,
      we investigated the roles of two Aspergillus fumigatus proteins that share high
      sequence similarity with S. cerevisiae Pdr5, an ABC transporter protein that is
      commonly overproduced in azole-resistant isolates in this yeast. The two A.
      fumigatus genes encoding the ABC transporters sharing the highest sequence
      similarity to S. cerevisiae Pdr5 are called abcA and abcB here. We constructed
      deletion alleles of these two different ABC transporter-encoding genes in three
      different strains of A. fumigatus. Loss of abcB invariably elicited increased
      azole susceptibility, while abcA disruption alleles had variable phenotypes.
      Specific antibodies were raised to both AbcA and AbcB proteins. These antisera
      allowed detection of AbcB in wild-type cells, while AbcA could be visualized only
      when overproduced from the hspA promoter in A. fumigatus. Overproduction of AbcA
      also yielded increased azole resistance. Green fluorescent protein fusions were
      used to provide evidence that both AbcA and AbcB are localized to the plasma
      membrane in A. fumigatus. Promoter fusions to firefly luciferase suggested that
      expression of both ABC transporter-encoding genes is inducible by azole
      challenge. Virulence assays implicated AbcB as a possible factor required for
      normal pathogenesis. This work provides important new insights into the
      physiological roles of ABC transporters in this major fungal pathogen. 

PMID- 24123269
TI  - Parasexuality and ploidy change in Candida tropicalis.
AB  - Candida species exhibit a variety of ploidy states and modes of sexual
      reproduction. Most species possess the requisite genes for sexual reproduction,
      recombination, and meiosis, yet only a few have been reported to undergo a
      complete sexual cycle including mating and sporulation. Candida albicans, the
      most studied Candida species and a prevalent human fungal pathogen, completes its
      sexual cycle via a parasexual process of concerted chromosome loss rather than a
      conventional meiosis. In this study, we examine ploidy changes in Candida
      tropicalis, a closely related species to C. albicans that was recently revealed
      to undergo sexual mating. C. tropicalis diploid cells mate to form tetraploid
      cells, and we show that these can be induced to undergo chromosome loss to
      regenerate diploid forms by growth on sorbose medium. The diploid products are
      themselves mating competent, thereby establishing a parasexual cycle in this
      species for the first time. Extended incubation (>120 generations) of C.
      tropicalis tetraploid cells under rich culture conditions also resulted in
      instability of the tetraploid form and a gradual reduction in ploidy back to the
      diploid state. The fitness levels of C. tropicalis diploid and tetraploid cells
      were compared, and diploid cells exhibited increased fitness relative to
      tetraploid cells in vitro, despite diploid and tetraploid cells having similar
      doubling times. Collectively, these experiments demonstrate distinct pathways by
      which a parasexual cycle can occur in C. tropicalis and indicate that nonmeiotic
      mechanisms drive ploidy changes in this prevalent human pathogen. 

PMID- 24123270
TI  - Laccases involved in 1,8-dihydroxynaphthalene melanin biosynthesis in Aspergillus
      fumigatus are regulated by developmental factors and copper homeostasis.
AB  - Aspergillus fumigatus produces heavily melanized infectious conidia. The conidial
      melanin is associated with fungal virulence and resistance to various
      environmental stresses. This 1,8-dihydroxynaphthalene (DHN) melanin is
      synthesized by enzymes encoded in a gene cluster in A. fumigatus, including two
      laccases, Abr1 and Abr2. Although this gene cluster is not conserved in all
      aspergilli, laccases are critical for melanization in all species examined. Here
      we show that the expression of A. fumigatus laccases Abr1/2 is upregulated upon
      hyphal competency and drastically increased during conidiation. The Abr1 protein
      is localized at the surface of stalks and conidiophores, but not in young hyphae,
      consistent with the gene expression pattern and its predicted role. The induction
      of Abr1/2 upon hyphal competency is controlled by BrlA, the master regulator of
      conidiophore development, and is responsive to the copper level in the medium. We
      identified a developmentally regulated putative copper transporter, CtpA, and
      found that CtpA is critical for conidial melanization under copper-limiting
      conditions. Accordingly, disruption of CtpA enhanced the induction of abr1 and
      abr2, a response similar to that induced by copper starvation. Furthermore,
      nonpigmented ctpADelta conidia elicited much stronger immune responses from the
      infected invertebrate host Galleria mellonella than the pigmented ctpADelta or
      wild-type conidia. Such enhancement in eliciting Galleria immune responses was
      independent of the ctpADelta conidial viability, as previously observed for the
      DHN melanin mutants. Taken together, our findings indicate that both copper
      homeostasis and developmental regulators control melanin biosynthesis, which
      affects conidial surface properties that shape the interaction between this
      pathogen and its host. 

PMID- 24123271
TI  - Expression of functional Plasmodium falciparum enzymes using a wheat germ cell
      free system.
AB  - One decade after the sequencing of the Plasmodium falciparum genome, 95% of
      malaria proteins in the genome cannot be expressed in traditional cell-based
      expression systems, and the targets of the best new leads for antimalarial drug
      discovery are either not known or not available in functional form. For a disease
      that kills up to 1 million people per year, routine expression of recombinant
      malaria proteins in functional form is needed both for the discovery of new
      therapeutics and for identification of targets of new drugs. We tested the
      general utility of cell-free systems for expressing malaria enzymes. Thirteen
      test enzyme sequences were reverse amplified from total RNA, cloned into a plant
      like expression vector, and subjected to cell-free expression in a wheat germ
      system. Protein electrophoresis and autoradiography confirmed the synthesis of
      products of expected molecular masses. In rare problematic cases, truncated
      products were avoided by using synthetic genes carrying wheat codons. Scaled-up
      production generated 39 to 354 MUg of soluble protein per 10 mg of translation
      lysate. Compared to rare proteins where cell-based systems do produce functional
      proteins, the cell-free yields are comparable or better. All 13 test products
      were enzymatically active, without failure. This general path to produce
      functional malaria proteins should now allow the community to access new tools,
      such as biologically active protein arrays, and lead to the discovery of new
      chemical functions, structures, and inhibitors of previously inaccessible malaria
      gene products. 

PMID- 24123272
TI  - Cultural competency in health care and its implications for pharmacy Part 3B:
      emphasis on pharmacy education policy, procedures, and climate.
AB  - The Institute of Medicine has stated that greater diversity within health care
      professionals leads to improved patient outcomes. Therefore, greater diversity
      within academia and student bodies is required to create future diverse health
      care professionals. Cultural sensitivity is required from recruitment to physical
      environment for administrators, faculty, staff, and students. University,
      college, and department recruitment, search committees, hiring practices, and
      admissions policies and procedures need to be assessed to determine whether they
      reflect the applicant pool and patient populations in their regions and whether
      they are culturally sensitive to a wide variety of cultures. The mission, vision,
      policies, procedures, curriculums, and environments should also be created or
      reviewed, modified, and/or expanded to ensure that no administrator, faculty
      member, staff member, or student is discriminated against or disadvantaged
      because of cultural beliefs or practices. In addition to discussing the interplay
      between cultural sensitivity and academic policies, procedures, and environments,
      this article briefly discusses specific cultural issues related to religion,
      spirituality, race, ethnicity, gender, age, marital status, veterans, physical,
      mental, and learning disabilities, and sexual orientation diversity. 

PMID- 24123273
TI  - Sample size estimation for time-dependent receiver operating characteristic.
AB  - In contrast to the usual ROC analysis with a contemporaneous reference standard,
      the time-dependent setting introduces the possibility that the reference standard
      refers to an event at a future time and may not be known for every patient due to
      censoring. The goal of this research is to determine the sample size required for
      a study design to address the question of the accuracy of a diagnostic test using
      the area under the curve in time-dependent ROC analysis. We adapt a previously
      published estimator of the time-dependent area under the ROC curve, which is a
      function of the expected conditional survival functions. This estimator
      accommodates censored data. The estimation of the required sample size is based
      on approximations of the expected conditional survival functions and their
      variances, derived under parametric assumptions of an exponential failure time
      and an exponential censoring time. We also consider different patient enrollment
      strategies. The proposed method can provide an adequate sample size to ensure
      that the test's accuracy is estimated to a prespecified precision. We present
      results of a simulation study to assess the accuracy of the method and its
      robustness to departures from the parametric assumptions. We apply the proposed
      method to design of a study of positron emission tomography as predictor of
      disease free survival in women undergoing therapy for cervical cancer.

PMID- 24123275
TI  - Gold-decorated chiral macroporous films by the self-assembly of functionalised
      block copolymers.
AB  - We describe a new and very versatile method to place chosen chemical
      functionalities at the edge of the pores of macroporous materials. The method is
      based on the synthesis and self-assembly of inorganic block copolymers (BCPs)
      having chiral rigid segments bearing controllable quantities of randomly
      distributed functional groups. The synthesis of a series of optically active
      block copolyphosphazenes (PP) with the general formula [N=P(R
      O2C20H12)(0.9)(FG)(0.2)]n-b-[N=PMePh]m (FG=-OC5H4N (6), -NC4H8S (7), and -NC4H8O
      (8)), was accomplished by the sequential living cationic polycondensation of N
      silylphosphoranimines, using the mono-end-capped initiator [Ph3P=N=PCl3][Cl] (3).
      The self-assembly of the phosphazene BCPs 6-8 led to chiral porous films. The
      functionality present on those polymers affected their self-assembly behaviour
      resulting in the formation of pores of different diameters (D(n)=111 (6), 53 (7)
      and 77 nm (8)). The specific functionalisation of the pores was proven by
      decorating the films with gold nanoparticles (AuNPs). Thus, the BCPs 6 and 7,
      having pyridine and thiomorpholine groups, respectively, were treated with
      HAuCl4, followed by reduction with NaBH4, yielding a new type of block
      copolyphosphazenes, which self-assembled into chiral porous films specifically
      decorated with AuNPs at the edge of the pores.

PMID- 24123274
TI  - Conformational dynamics is more important than helical propensity for the folding
      of the all alpha-helical protein Im7.
AB  - Im7 folds via an on-pathway intermediate that contains three of the four native
      alpha-helices. The missing helix, helix III, is the shortest and its failure to
      be formed until late in the pathway is related to frustration in the structure.
      Im7H3M3, a 94-residue variant of the 87-residue Im7 in which helix III is the
      longest of the four native helices, also folds via an intermediate. To
      investigate the structural basis for this we calculated the frustration in the
      structure of Im7H3M3 and used NMR to investigate its dynamics. We found that the
      native state of Im7H3M3 is highly frustrated and in equilibrium with an
      intermediate state that lacks helix III, similar to Im7. Model-free analysis
      identified residues with chemical exchange contributions to their relaxation that
      aligned with the residues predicted to have highly frustrated interactions, also
      like Im7. Finally, we determined properties of urea-denatured Im7H3M3 and
      identified four clusters of interacting residues that corresponded to the alpha
      helices of the native protein. In Im7 the cluster sizes were related to the
      lengths of the alpha-helices with cluster III being the smallest but in Im7H3M3
      cluster III was also the smallest, despite this region forming the longest helix
      in the native state. These results suggest that the conformational properties of
      the urea-denatured states promote formation of a three-helix intermediate in
      which the residues that form helix III remain non-helical. Thus it appears that
      features of the native structure are formed early in folding linked to collapse
      of the unfolded state. 

PMID- 24123276
TI  - Gender and menopause impact severity of fibrosis among patients with nonalcoholic
      steatohepatitis.
AB  - Estrogens inhibit stellate cell activation and fibrogenesis. Thus, gender and
      reproductive states may influence the degree of fibrosis in patients with
      nonalcoholic steatohepatitis (NASH). To investigate the association between
      gender, menopause, and the severity of liver fibrosis in patients with NASH, we
      analyzed 541 adult patients enrolled from our Duke Liver Clinics (n = 338) and
      the Duke Metabolic and Weight Loss Surgery Program (n = 203) who had a histologic
      diagnosis of NASH. Multiple ordinal logistic regression models were used to
      assess the association between gender, menopause, and severity of liver fibrosis.
      Overall, men, premenopausal, and postmenopausal women composed 35.1%, 28.4%, and
      36.5% of the population, respectively. The mean age was 48 years and 22% had
      advanced fibrosis. After adjusting for covariates (enrolling site, grades of
      portal inflammation, and hepatocyte ballooning) and potential confounders (race,
      body mass index, diabetes/prediabetes, hypertension), adjusted cumulative odd
      ratio (ACOR) and 95% confidence interval (CI) for greater fibrosis severity was
      1.4 (0.9, 2.1) (P = 0.17) for postmenopausal women and 1.6 (1.0, 2.5) (P = 0.03)
      for men, having premenopausal women as a reference. There was borderline
      interaction between gender and age group divided by age 50, the average age at
      menopause in the U.S. (P = 0.08): ACOR and 95% CI of having greater fibrosis
      severity in men compared to women was 1.8 (1.1, 2.9) for patients with age <50
      years (P = 0.02) and 1.2 (0.7, 2.1) for patients with age >=50 years (P = 0.59).
      CONCLUSION: Men are at a higher risk of having more severe fibrosis compared to
      women before menopause, while postmenopausal women have a similar severity of
      liver fibrosis compared to men. These findings may be explained by the protective
      effects of estrogen against fibrogenesis.

PMID- 24123277
TI  - Time course of structural and functional maturation of human olfactory epithelial
      cells in vitro.
AB  - The unique ability of olfactory neurons to regenerate in vitro has allowed their
      use for the study of olfactory function, regeneration, and neurodegenerative
      disorders; thus, characterization of their properties is important. This present
      study attempts to establish the timeline of structural (protein expression) and
      functional (odorant sensitivity) maturation of human olfactory epithelial cells
      (hOE) in vitro using biopsy-derived cultured tissue. Cells were grown for 7 days;
      on each day, cells were tested for odorant sensitivity using calcium imaging
      techniques and then protein expression of each cell was tested using
      immunocytochemistry for proteins typically used for characterizing olfactory
      cells. Previous studies have shown that mature olfactory neurons in vitro attain
      a unique "phase-bright" morphology and express the olfactory marker protein
      (OMP). By day 3 in vitro, a variety of cells were odorant-sensitive, including
      both "phase-bright" and "phase-dark" cells that have previously been considered
      glial-like cells. The functional maturation of these hOEs appears to take place
      within 4 days. Interestingly, the emergence of an odorant sensitivity profile of
      both phase-bright and phase-dark cells preceded the expression of marker protein
      expression for OMP (which is expressed only by mature neurons in vivo). This
      structural maturation took 5 days, suggesting that the development of odorant
      sensitivity is not coincident with the expression of marker molecules that are
      hallmarks of structural maturation. These results have important implications for
      the use of hOEs as in vitro models of olfactory and neuronal function.

PMID- 24123278
TI  - MRI in differentiating ovarian borderline from benign mucinous cystadenoma:
      pathological correlation.
AB  - PURPOSE: To investigate MRI in differentiating borderline mucinous cystadenoma
      (MC) from benign MC of the ovary. MATERIALS AND METHODS: We studied MR images of
      26 benign MCs and 24 borderline MCs of the ovary. The following MRI features of
      tumors were evaluated and compared between two groups: laterality, shape, size,
      loculation, signal intensity of the fluid, thickness of the septation and the
      wall, and vegetations. The results of the MRI were then compared with the
      pathological findings. RESULTS: Honeycomb loculi, high signal intensity on T1WI,
      and low signal intensity on T2WI of the intracystic content, thickened septation
      or wall (>=5 mm), and vegetations (>=5 mm) were significantly more common in
      borderline MC than in benign MC with the sensitivity and specificity of
      identifying borderline MC of 50.0% and 80.8%, 41.7% and 96.2%, 45.8% and 96.2%,
      and 62.5% and 96.2%, respectively. The presence of any one of the following
      features-honeycomb loculi with a low signal intensity on T2WI, thickened
      septation or wall (>=5 mm), and vegetations (>=5 mm)-yielded the sensitivity,
      specificity, and accuracy of identifying borderline MC of 91.7%, 92.3%, and
      92.0%, respectively. CONCLUSION: MRI has the ability to accurately demonstrate
      the morphological characteristics of ovarian MC and reliably differentiate
      borderline MC from benign MC.

PMID- 24123279
TI  - High-resolution MRI of uveal melanoma using a microcoil phased array at 7 T.
AB  - High-field MRI is a promising technique for the characterisation of ocular
      tumours, both in vivo and after enucleation. For in vivo imaging at 7 T, a
      dedicated three-element microcoil array was constructed as a high-sensitivity
      receive-only device. Using a dedicated blink/fixation protocol, high-resolution
      in vivo images could be acquired within 3 min in volunteers and patients with no
      requirement for post-acquisition image registration. Quantitative measures of
      axial length, aqueous depth and lens thickness in a healthy volunteer were found
      to agree well with standard ocular biometric techniques. In a patient with uveal
      melanoma, in vivo MRI gave excellent tumour/aqueous body contrast. Ex vivo
      imaging of the enucleated eye showed significant heterogeneity within the tumour.

PMID- 24123280
TI  - Antifreeze protein-induced selective crystallization of a new thermodynamically
      and kinetically less preferred molecular crystal.
AB  - The formation of a new, dihydrate crystalline form of 5-methyluridine (m(5)U) was
      selectively induced by a protein additive, antifreeze protein (AFP) in a highly
      efficient manner (in 10(-6) molar scale, whereas known kinetic additives need 0.1
      molar scale). The hemihydrate form (form I, the only previously known crystalline
      form of m(5)U) and the dihydrate form of m(5)U (form II) obtained herein were
      characterized using X-ray crystallography and differential scanning calorimetry
      (DSC). Compared to form I, remarkably, form II is thermodynamically and
      kinetically less preferred. The presence of AFP can selectively inhibit the
      appearance of form I and hence allows the growth of form II, the pure form of
      which cannot grow directly from m(5) U supersaturated solutions under the same
      conditions. An explanation supported by both experimental and theoretical results
      is provided for the AFP-induced selection process. Implications on AFP-induced
      ice shape changes are also discussed. Control of crystallization from
      supersaturated solutions is of great interest in both fundamental research and
      practical applications in fields like chemistry, pharmacology and materials
      science. These findings suggest that crystallization processes with AFPs could be
      valuable for selective growth of hydrates and polymorphs of important
      pharmaceutical compounds.

PMID- 24123281
TI  - Geometric profile of the tibial plateau cartilage surface is associated with the
      risk of non-contact anterior cruciate ligament injury.
AB  - The purpose of this study was to determine if geometry of the articular surfaces
      of the tibial plateau is associated with non-contact anterior cruciate ligament
      (ACL) injury. This was a longitudinal cohort study with a nested case-control
      analysis. Seventy-eight subjects who suffered a non-contact ACL tear and a
      corresponding number of controls matched by age, sex, and sport underwent 3 T MRI
      of both knees. Surface geometry of the tibial articular cartilage was
      characterized with polynomial equations and comparisons were made between knees
      on the same person and between ACL-injured and control subjects. There was no
      difference in surface geometry between the knees of the control subjects. In
      contrast, there were significant differences in the surface geometry between the
      injured and normal knees of the ACL-injured subjects, suggesting that the ACL
      injury changed the cartilage surface profile. Therefore, comparisons were made
      between the uninjured knees of the ACL-injured subjects and the corresponding
      knees of their matched controls and this revealed significant differences in the
      surface geometry for the medial (p < 0.006) and lateral (p < 0.001) compartments.
      ACL-injured subjects tended to demonstrate a posterior-inferior directed
      orientation of the articular surface relative to the long axis of the tibia,
      while the control subjects were more likely to show a posterior-superior directed
      orientation.

PMID- 24123282
TI  - Crystal structure of the N-terminal methyltransferase-like domain of anamorsin.
AB  - Anamorsin is a recently identified molecule that inhibits apoptosis during
      hematopoiesis. It contains an N-terminal methyltransferase-like domain and a C
      terminal Fe-S cluster motif. Not much is known about the function of the protein.
      To better understand the function of anamorsin, we have solved the crystal
      structure of the N-terminal domain at 1.8 A resolution. Although the overall
      structure resembles a typical S-adenosylmethionine (SAM) dependent
      methyltransferase fold, it lacks one alpha-helix and one beta-strand. As a
      result, the N-terminal domain as well as the full-length anamorsin did not show S
      adenosyl-L-methionine (AdoMet) dependent methyltransferase activity. Structural
      comparisons with known AdoMet dependent methyltransferases reveals subtle
      differences in the SAM binding pocket that preclude the N-terminal domain from
      binding to AdoMet. The N-terminal methyltransferase-like domain of anamorsin
      probably functions as a structural scaffold to inhibit methyl transfers by out
      competing other AdoMet dependant methyltransferases or acts as bait for protein
      protein interactions.

PMID- 24123283
TI  - Intermediate form between alternating hemiplegia of childhood and rapid-onset
      dystonia-parkinsonism.

PMID- 24123284
TI  - The relationship between and clinical significance of MicroRNA-32 and phosphatase
      and tensin homologue expression in colorectal cancer.
AB  - MicroRNAs (miRNAs, miRs) are suspected to play important roles in carcinogenesis.
      MiR-32 has altered expression in colorectal cancer (CRC); however, the clinical
      significance of miR-32 expression in the process of carcinogenesis is poorly
      understood. In this study, we determined the levels of, the correlation between,
      and the clinical significance of the expression of miR-32 and phosphatase and
      tensin homologue (PTEN), a tumor suppressor targeted by miR-32, in CRC. The
      levels of miR-32 and PTEN gene expression in 35 colorectal carcinoma samples, 35
      corresponding cancer-adjacent tissue samples, 27 colorectal adenoma samples, and
      16 normal tissue samples were quantified using real-time quantitative reverse
      transcriptase-polymerase chain reaction. PTEN protein expression was determined
      using western blot and immunohistochemistry (IHC). The relationship between the
      miR-32 and PTEN protein expression and clinicopathological factors was analyzed.
      Significant upregulation of miR-32 expression and reduction of PTEN were
      identified in CRC tissues. High miR-32 levels were significantly associated with
      lymph node and distant metastasis, and Kaplan-Meier analysis indicated that
      patients with high miR-32 expression had a poor overall survival. Low PTEN
      protein expression was also significantly correlated with distant metastasis. An
      inverse relationship between miR-32 and PTEN protein expression was identified.
      In addition, IHC analysis revealed weak or indiscernible PTEN staining in tumor
      tissue. MiR-32 overexpression was correlated with specific CRC
      clinicopathological features and may be a marker of poor prognosis in CRC
      patients. MiR-32 and PTEN expression were inversely correlated, and miR-32 may be
      associated with the development of CRC.

PMID- 24123285
TI  - Changes of oral microcirculation in chemotherapy patients: A possible correlation
      with mucositis?
AB  - The aim of this investigation is to appraise labial oral microcirculation in
      chemotherapy patients to clarify the effects of cytotoxic agents on oral
      microvessels. Twenty-five patients with diagnosis of head and neck tumors were
      recruited in the study. All the patients were submitted to chemotherapy. Labial
      oral microcirculation was evaluated on labial mucosa using oral
      videocapillaroscopy. The statistical significance was checked with the Mann
      Whitney U-test (P < 0.05). The analysis of videocapillaroscopic patterns showed
      statistically significant variations relative to the diameter of the incoming
      loop; the diameter of the outgoing loop; and loop tortuosity. This study shows
      that capillary alterations to patients who receive chemotherapy occur in labial
      oral microcirculation.

PMID- 24123286
TI  - Raf kinase inhibitory protein role in the molecular subtyping of breast cancer.
AB  - In this study, we examined the association between the RKIP expression and the
      molecular subtypes of breast cancer. Microarray gene expression data of 2,333
      human breast cancer from 26 different cohorts performed on Affymetrix U133A or
      U133Plus2 platforms were downloaded from Array Express and Gene Expression
      Omnibus and the molecular subtype of breast cancer for the samples was determined
      by single sample Gene Set Enrichment Analysis. Differences in recurrence-free
      survival (RFS) were tested using the Log-rank test in univariate analysis and
      displayed using Kaplan-Meier curves. Cox proportional-hazards model was used to
      calculate the hazard ratio using univariate and multivariate analysis. Loss or
      reduced RKIP expression was associated with reduced RFS in breast cancer using
      univariate and multivariate analyses, which was independent of lymph node (LN)
      metastasis status. Basal-like, Claudin-low, and Her-2-enriched tumors had
      significantly lower RKIP levels compared to other subclasses (P < 0.0001).
      Conversely, the Luminal subclass exhibited the highest expression levels of RKIP
      (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal
      like breast cancer subtype, RKIP expression was not informative. RKIP expression
      was prognostic in ER+ and ER- subgroups. RKIP expression had no significant
      prognostic power within Basal-like, Claudine-low, Luminal B, or Her-2-enriched
      breast cancer subtypes. However, its expression pinpointed excellent from
      intermediate-poor Luminal A survivors, in both ER+ (P = 0.035) and ER- (P =
      0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP
      expression adds significant value to the molecular subclassification of breast
      cancer especially for the Luminal A subtype.

PMID- 24123287
TI  - Propagation of calibration errors in prospective motion correction using external
      tracking.
AB  - PURPOSE: Prospective motion correction of MRI scans using an external tracking
      device (such as a camera) is becoming increasingly popular, especially for
      imaging of the head. In order for external tracking data to be transformed into
      the MR scanner reference frame, the pose (i.e., position and orientation) of the
      camera relative to the scanner--or cross-calibration--must be accurate. In this
      study, we investigated how errors in cross-calibration affect the accuracy of
      motion correction feedback in MRI. THEORY AND METHODS: An operator equation is
      derived describing how calibration errors relate to errors in applied motion
      compensation. By taking advantage of spherical symmetry and performing a Taylor
      approximation for small rotation angles, a closed form expression and upper limit
      for the residual tracking error is provided. RESULTS: Experiments confirmed
      theoretical predictions of a bilinear dependence of the residual rotational
      component on the calibration error and the motion performed, modulated by a
      sinusoidal dependence on the angle between the calibration error axis and motion
      axis. The residual translation error is bounded by the sum of the rotation angle
      multiplied by the translational calibration error plus the linear head
      displacement multiplied by the calibration error angle. CONCLUSION: The results
      make it possible to calculate the required cross-calibration accuracy for
      external tracking devices for a range of motions. Scans with smaller expected
      movements require less accuracy in cross-calibration than scans involving larger
      movements. Typical clinical applications require that the calibration accuracy is
      substantially below 1 mm and 1 degrees .

PMID- 24123288
TI  - Sex dimorphism in the white matter: fractional anisotropy and brain size.
AB  - PURPOSE: To examine sex differences in fractional anisotropy of the white matter
      across the whole brain, controlling for head size variation. MATERIALS AND
      METHODS: A total of 238 normal subjects aged 40-49 years were included in this
      study. Diffusion tensor images were acquired at 3 Tesla using a single-shot spin
      echo echo-planar sequence. With use of tract-based spatial statistics (TBSS), sex
      differences in fractional anisotropy of the white matter were examined across the
      whole brain, without and with adjustment of total intracranial volume. Voxelwise
      analyses of the processed fractional anisotropy data were performed using
      permutation-based, voxelwise nonparametric testing. RESULTS: TBSS analysis
      without adjustment for total intracranial volume showed several regions with a
      significant effect of sex on fractional anisotropy; these included the splenium
      of the corpus callosum, bilateral superior corona radiata, and posterior limbs of
      the internal capsule, midbrain, and cerebellum. Significantly higher fractional
      anisotropy was seen in males compared with females in these regions. TBSS
      analysis with adjustment for total intracranial volume, however, showed a greatly
      reduced number of such regions. CONCLUSION: The results of our study suggest that
      sex differences in fractional anisotropy of the white matter reported by previous
      studies may partly reflect differences in head size, not microscopic differences.

PMID- 24123289
TI  - Optimal auxiliary-covariate-based two-phase sampling design for semiparametric
      efficient estimation of a mean or mean difference, with application to clinical
      trials.
AB  - To address the objective in a clinical trial to estimate the mean or mean
      difference of an expensive endpoint Y, one approach employs a two-phase sampling
      design, wherein inexpensive auxiliary variables W predictive of Y are measured in
      everyone, Y is measured in a random sample, and the semiparametric efficient
      estimator is applied. This approach is made efficient by specifying the phase two
      selection probabilities as optimal functions of the auxiliary variables and
      measurement costs. While this approach is familiar to survey samplers, it
      apparently has seldom been used in clinical trials, and several novel results
      practicable for clinical trials are developed. We perform simulations to identify
      settings where the optimal approach significantly improves efficiency compared to
      approaches in current practice. We provide proofs and R code. The optimality
      results are developed to design an HIV vaccine trial, with objective to compare
      the mean 'importance-weighted' breadth (Y) of the T-cell response between
      randomized vaccine groups. The trial collects an auxiliary response (W) highly
      predictive of Y and measures Y in the optimal subset. We show that the optimal
      design-estimation approach can confer anywhere between absent and large
      efficiency gain (up to 24 % in the examples) compared to the approach with the
      same efficient estimator but simple random sampling, where greater variability in
      the cost-standardized conditional variance of Y given W yields greater efficiency
      gains. Accurate estimation of E[Y | W] is important for realizing the efficiency
      gain, which is aided by an ample phase two sample and by using a robust fitting
      method.

PMID- 24123291
TI  - Value of EQ-5D in Mexican city older population with and without dementia (SADEM
      study).
AB  - BACKGROUND: The EuroQoL-5D (EQ-5D) is a brief, multi-attribute, preference-based
      health status measurement. The objective of this study was to assess the validity
      and reliability of EQ-5D in older adults with and without dementia in Mexico
      City. METHODS: The Study on Aging and Dementia in Mexico (SADEM) was a survey of
      3101, Mexican adults (60 + years old). An in-home face-to-face interview was
      administered. EQ-5D using ranking to rate states on a 100-point visual analogue
      scale; Daily Living Activities (ADL), Instrumental Activities of Daily Living
      (IADL), Mini Mental State Examination (MMSE), Short Form of the quality of life
      survey (SF-36), and Charlson comorbility index were used for comparison. The
      validity and reliability of EQ-5D were tested. We identified states of health for
      direct valuation; state 11111 ("no problems") had to be included because it was
      essential to the reseating (onto a 0-1 scale) of the visual analogue scale data.
      We included all plausible combinations of levels across each of the five EQ-5D
      dimensions and evaluated any significant interaction effects and factorial
      designs, based on balanced complete blocks. RESULTS: The EQ-5D was applied to
      3101 older people, of whom 109 (3.4%) had dementia. The general reliability of EQ
      5D for cases was 0.80 and for controls 0.76, for each dimension. We had a total
      of 103 combinations for controls and 45 for cases. The percentage for the state
      of health "no problems" (11111) for controls was 30.4%, and had the highest
      percentage of cases (8.8%). CONCLUSION: The resulting valuations form the basis
      for clinical use and facilitate the interpretation and evaluation of health care.

PMID- 24123290
TI  - The interdomain interface in bifunctional enzyme protein 3/4A (NS3/4A) regulates
      protease and helicase activities.
AB  - Hepatitis C (HCV) protein 3/4A (NS3/4A) is a bifunctional enzyme comprising two
      separate domains with protease and helicase activities, which are essential for
      viral propagation. Both domains are stable and have enzymatic activity
      separately, and the relevance and implications of having protease and helicase
      together as a single protein remains to be explored. Altered in vitro activities
      of isolated domains compared with the full-length NS3/4A protein suggest the
      existence of interdomain communication. The molecular mechanism and extent of
      this communication was investigated by probing the domain-domain interface
      observed in HCV NS3/4A crystal structures. We found in molecular dynamics
      simulations that the two domains of NS3/4A are dynamically coupled through the
      interface. Interestingly, mutations designed to disrupt this interface did not
      hinder the catalytic activities of either domain. In contrast, substrate cleavage
      and DNA unwinding by these mutants were mostly enhanced compared with the wild
      type protein. Disrupting the interface did not significantly alter RNA unwinding
      activity; however, the full-length protein was more efficient in RNA unwinding
      than the isolated protease domain, suggesting a more direct role in RNA
      processing independent of the interface. Our findings suggest that HCV NS3/4A
      adopts an "extended" catalytically active conformation, and interface formation
      acts as a switch to regulate activity. We propose a unifying model connecting HCV
      NS3/4A conformational states and protease and helicase function, where interface
      formation and the dynamic interplay between the two enzymatic domains of HCV
      NS3/4A potentially modulate the protease and helicase activities in vivo. 

PMID- 24123292
TI  - Design and synthesis of lipidic organoalkoxysilanes for the self-assembly of
      liposomal nanohybrid cerasomes with controlled drug release properties.
AB  - This paper reports the facile design and synthesis of a series of lipidic
      organoalkoxysilanes with different numbers of triethoxysilane headgroups and
      hydrophobic alkyl chains linked by glycerol and pentaerythritol for the
      construction of cerasomes with regulated surface siloxane density and controlled
      release behavior. It was found that the number of triethoxysilane headgroups
      affected the properties of the cerasomes for encapsulation efficiency, drug
      loading capacity, and release behavior. For both water-soluble doxorubicin (DOX)
      and water-insoluble paclitaxel (PTX), the release rate from the cerasomes
      decreased as the number of triethoxysilane headgroups increased. The slower
      release rate from the cerasomes was attributed to the higher density of the
      siloxane network on the surface of the cerasomes, which blocks the drug release
      channels. In contrast to the release results with DOX, the introduction of one
      more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower
      release rate of PTX from the cerasomes due to the formation of a more compact
      cerasome bilayer. An MTT viability assay showed that all of these drug-loaded
      cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning
      of the chemical structure of the cerasome-forming lipids would foster a new
      strategy to precisely regulate the release rate of drugs from cerasomes. 

PMID- 24123293
TI  - Have they done what they should? Moral reasoning in the context of translating
      older persons' everyday problems into eligible needs for home modification
      services.
AB  - This study explores how moral reasoning is expressed in matching health care with
      the problems older persons experience in their everyday life. Narrative data were
      collected from older persons who had applied for home modification services and
      from professionals involved in these services in Sweden. A theoretical framework,
      based on theories on the anthropology of morals, was applied to explore how the
      participants made conclusions about "what should be done." Moral reasoning was
      found to be guided by ideologies related to the historical and cultural context
      of the Swedish welfare state. Different interpretations of how these values
      should be expressed in specific situations led to different conclusions about
      what should be done. The study highlights the importance of understanding how
      values are enacted rather than what values different social agents have in order
      to understand how health care services can be designed and provided to support
      older persons' everyday life. 

PMID- 24123294
TI  - Control of miscibility and aggregation via the material design and coating
      process for high-performance polymer blend solar cells.
AB  - A power conversion efficiency of 3.6% for an all-polymer solar cell, which is the
      highest ever reported, is achieved by introducing a conjugated side chain into a
      p-type polymer to improve the miscibility of the polymer blend and by adding
      small amounts of 1,8-diiodooctane to increase the aggregation of n-type polymer. 

PMID- 24123295
TI  - Real-time flow MRI of the aorta at a resolution of 40 msec.
AB  - PURPOSE: To evaluate a novel real-time phase-contrast magnetic resonance imaging
      (MRI) technique for the assessment of through-plane flow in the ascending aorta.
      MATERIALS AND METHODS: Real-time MRI was based on a radial fast low-angle shot
      (FLASH) sequence with about 30-fold undersampling and image reconstruction by
      regularized nonlinear inversion. Phase-contrast maps were obtained from two
      (interleaved or sequential) acquisitions with and without a bipolar velocity
      encoding gradient. Blood flow in the ascending aorta was studied in 10 healthy
      volunteers at 3 T by both real-time MRI (15 sec during free breathing) and
      electrocardiogram (ECG)-synchronized cine MRI (with and without breath holding).
      Flow velocities and stroke volumes were evaluated using standard postprocessing
      software. RESULTS: The total acquisition time for a pair of phase-contrast images
      was 40.0 msec (TR/TE = 2.86/1.93 msec, 10 degrees  flip angle, 7 spokes per
      image) for a nominal in-plane resolution of 1.3 mm and a section thickness of 6
      mm. Quantitative evaluations of spatially averaged flow velocities and stroke
      volumes were comparable for real-time and cine methods when real-time MRI data
      were averaged across heartbeats. For individual heartbeats real-time phase
      contrast MRI resulted in higher peak velocities for values above 120 cm s(-1).
      CONCLUSION: Real-time phase-contrast MRI of blood flow in the human aorta yields
      functional parameters for individual heartbeats. When averaged across heartbeats
      real-time flow velocities and stroke volumes are comparable to values obtained by
      conventional cine MRI.

PMID- 24123296
TI  - Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic
      targeting.

PMID- 24123297
TI  - Role of histidine for charge regulation of unstructured peptides at interfaces
      and in bulk.
AB  - Histidine-rich, unstructured peptides adsorb to charged interfaces such as
      mineral surfaces and microbial cell membranes. At a molecular level, we
      investigate the adsorption mechanism as a function of pH, salt, and multivalent
      ions showing that (1) proton charge fluctuations are-in contrast to the majority
      of proteins-optimal at neutral pH, promoting electrostatic interactions with
      anionic surfaces through charge regulation and (2) specific zinc(II)-histidine
      binding competes with protons and ensures an unusually constant charge
      distribution over a broad pH interval. In turn, this further enhances surface
      adsorption. Our analysis is based on atomistic molecular dynamics simulations,
      coarse grained Metropolis Monte Carlo, and classical polymer density functional
      theory. This multiscale modeling provides a consistent picture in good agreement
      with experimental data on Histatin 5, an antimicrobial salivary peptide.
      Biological function is discussed and we suggest that charge regulation is a
      significant driving force for the remarkably robust activity of histidine-rich
      antimicrobial peptides.

PMID- 24123298
TI  - Assessment of relational intimacy: factor analysis of the personal assessment of
      intimacy in relationships questionnaire.

PMID- 24123299
TI  - Zebrafish brain proteomics reveals central proteins involved in
      neurodegeneration.
AB  - Understanding the complex biology of the brain requires analyzing its structural
      and functional complexity at the protein level. The large-scale analysis of the
      brain proteome, coupled with characterization of central brain proteins, provides
      insight into fundamental brain processes and processes linked to
      neurodegenerative diseases. Here we provide a map of the zebrafish brain proteome
      by using two-dimensional gel electrophoresis (2DE), followed by the
      identification of 95 brain proteins using mass spectrometry (LC-ESI MS/MS). Our
      data show extensive phosphorylation of brain proteins but less prominent
      glycosylation. Furthermore, ~51% of the identified proteins are predicted to have
      one or more ubiquitination sites whereas ~90% are predicted to have one or more
      SUMOylation sites. Our findings provide a valuable proteome map of the zebrafish
      brain and associated posttranslational modifications demonstrating that zebrafish
      proteomic approaches can aid in our understanding of proteins central to
      important neuronal processes and those associated with neurodegenerative
      disorders.

PMID- 24123300
TI  - Magnetic resonance elastography of liver in healthy Asians: normal liver
      stiffness quantification and reproducibility assessment.
AB  - PURPOSE: To determine normal liver stiffness values evaluated with magnetic
      resonance elastography (MRE) in healthy normal Asian volunteers and assess its
      reproducibility. MATERIALS AND METHODS: Liver stiffness was evaluated with MRE in
      41 healthy Asians (23 females, 18 males; mean age, 41.8 years, and mean body mass
      index [BMI], 23.4 kg/m(2) ) on a 1.5T clinical scanner. The correlations between
      mean liver stiffness and age, gender, BMI, and fat fraction percentage of the
      liver were studied. Another 12 volunteers underwent liver MRE exams on two
      separate days 4-6 weeks apart under similar conditions for reproducibility
      assessment. Intraclass correlation coefficient (ICC) analysis was performed and
      within-subject coefficient of variation (CV) of stiffness was estimated. RESULTS:
      The mean +/- standard deviation (SD) of liver stiffness in normal healthy Asian
      subjects was 2.09 +/- 0.22 kPa (95% confidence interval [CI], 2.04-2.15 kPa;
      range 1.68-2.48 kPa). The mean liver stiffness did not significantly correlate
      with age, gender, BMI, or fat content of the liver. The ICC for mean liver
      stiffness was 0.90 (95% CI, 0.78-0.96) and CV ranged from 2.2%-11.4%. CONCLUSION:
      The liver stiffness in normal Asians is not affected by age, gender, BMI, or fat
      content. Liver stiffness with MRE is highly reproducible.

PMID- 24123301
TI  - Zinc oxide nanoparticles toxicity to Daphnia magna: size-dependent effects and
      dissolution.
AB  - As the production of zinc oxide nanoparticles (ZnO-NPs) and other metal oxides is
      exponentially increasing, it is important to investigate potential environmental
      and health impacts of such nanoparticles. Nanoparticles' properties (e.g., size,
      dissolution rate) may change in different water media, and their characterization
      is essential to derive conclusions about toxicity results. Therefore, an aquatic
      model organism, Daphnia magna, was used to investigate the effect of ZnO-NPs with
      2 different particle sizes (30 nm and 80-100 nm) and then compare these effects
      with ZnO microsized particles (>200 nm) and the ionic counterpart (in the form of
      ZnCl2 ) on immobilization, feeding inhibition, and reproduction endpoints. The 48
      h median lethal concentration (LC50) for immobilization ranged between 0.76 mg Zn
      L(-1) for the ionic zinc and 1.32 mg Zn L(-1) for ZnO-NPs of 80 nm to 100 nm. For
      the chronic exposures, the reproduction output was impaired similarly among zinc
      exposures and possibly driven mainly by the zinc ionic form. The concentrations
      used showed a total dissolution after 48 h. On the other hand, feeding activity
      was more affected by the 30 nm ZnO-NPs than by the ionic zinc, showing that the
      particulate form was also playing an important role in the feeding inhibition of
      D. magna. Dissolution and particle size in the daphnia test media were found to
      be essential to derive conclusions on toxicity. Therefore, they can possibly be
      considered critical for evaluating nanoparticles' toxicity and fate.

PMID- 24123302
TI  - A noble-metal-free system for photocatalytic hydrogen production from water.
AB  - A series of heteroleptic copper(I) complexes with bidentate PP and NN chelate
      ligands was prepared and successfully applied as photosensitizers in the light
      driven production of hydrogen, by using [Fe3(CO)12] as a water-reduction catalyst
      (WRC). These systems efficiently reduces protons from water/THF/triethylamine
      mixtures, in which the amine serves as a sacrificial electron donor (SR).
      Turnover numbers (for H) up to 1330 were obtained with these fully noble-metal
      free systems. The new complexes were electrochemically and photophysically
      characterized. They exhibited a correlation between the lifetimes of the MLCT
      excited state and their efficiency as photosensitizers in proton-reduction
      systems. Within these experiments, considerably long excited-state lifetimes of
      up to 54 MUs were observed. Quenching studies with the SR, in the presence and
      absence of the WRC, showed that intramolecular deactivation was more efficient in
      the former case, thus suggesting the predominance of an oxidative quenching
      pathway.

PMID- 24123303
TI  - Highly hydrogenated graphene through microwave exfoliation of graphite oxide in
      hydrogen plasma: towards electrochemical applications.
AB  - Hydrogenated graphenes exhibit a variety of properties with potential
      applications in devices, ranging from a tunable band gap to fluorescence,
      ferromagnetism, and the storage of hydrogen. We utilize a one-step microwave
      irradiation process in hydrogen plasma to create highly hydrogenated graphene
      from graphite oxides. The procedure serves the dual purposes of deoxygenation and
      concurrent hydrogenation of the carbon backbone. The effectiveness of the
      hydrogenation process is investigated on three different graphite oxides (GOs),
      which are synthesized by using the Staudenmaier, Hofmann, and Hummers methods. A
      systematic characterization of our hydrogenated graphenes is performed using
      UV/Vis spectroscopy, SEM, AFM, Raman spectroscopy, FTIR spectroscopy, X-ray
      photoelectron spectroscopy (XPS), combustible elemental analysis, and electrical
      conductivity measurements. The highest hydrogenation extent is observed in
      hydrogenated graphene produced from the Hummers-method GO, with a hydrogen
      content of 19 atomic % in the final product. In terms of the removal of oxygen
      groups, microwave exfoliation yields graphenes with very similar oxygen contents
      despite differences in their parent GOs. In addition, we examine the prospective
      application of hydrogenated graphenes as electrochemical transducers through a
      cyclic voltammetry (CV) study. The highly hydrogenated graphenes exhibit fast
      heterogeneous electron-transfer rates, suggestive of their suitability for
      electrochemical applications in electrodes, supercapacitors, batteries, and
      sensors. 

PMID- 24123304
TI  - Development of the trigeminal motor neurons in parrots: implications for the role
      of nervous tissue in the evolution of jaw muscle morphology.
AB  - Vertebrates have succeeded to inhabit almost every ecological niche due in large
      part to the anatomical diversification of their jaw complex. As a component of
      the feeding apparatus, jaw muscles carry a vital role for determining the mode of
      feeding. Early patterning of the jaw muscles has been attributed to cranial
      neural crest-derived mesenchyme, however, much remains to be understood about the
      role of nonneural crest tissues in the evolution and diversification of jaw
      muscle morphology. In this study, we describe the development of trigeminal motor
      neurons in a parrot species with the uniquely shaped jaw muscles and compare its
      developmental pattern to that in the quail with the standard jaw muscles to
      uncover potential roles of nervous tissue in the evolution of vertebrate jaw
      muscles. In parrot embryogenesis, the motor axon bundles are detectable within
      the muscular tissue only after the basic shape of the muscular tissue has been
      established. This supports the view that nervous tissue does not primarily
      determine the spatial pattern of jaw muscles. In contrast, the trigeminal motor
      nucleus, which is composed of somata of neurons that innervate major jaw muscles,
      of parrot is more developed compared to quail, even in embryonic stage where no
      remarkable interspecific difference in both jaw muscle morphology and motor nerve
      branching pattern is recognized. Our data suggest that although nervous tissue
      may not have a large influence on initial patterning of jaw muscles, it may play
      an important role in subsequent growth and maintenance of muscular tissue and
      alterations in cranial nervous tissue development may underlie diversification of
      jaw muscle morphology.

PMID- 24123305
TI  - q-Space diffusion MRI (QSI) of the disease progression in the spinal cords of the
      Long Evans shaker: diffusion time and apparent anisotropy.
AB  - q-Space diffusion MRI (QSI) was used to study the spinal cords of Long Evans
      shaker (les) rats, a model of dysmyelination, and their age-matched controls at
      different maturation stages. Diffusion was measured parallel and perpendicular to
      the fibers of the spinal cords of the two groups and at different diffusion
      times. The results showed that QSI is able to detect the dysmyelination process
      that occurs in this model in the different stages of the disease. The differences
      in the diffusion characteristics of the spinal cords of the two groups were found
      to be larger when the diffusion time was increased from 22 to 100 ms. We found
      that the radial mean displacement is a much better parameter than the QSI
      fractional anisotropy (FA) to document the differences between the two groups. We
      observed that the degree of myelination affects the diffusion characteristics of
      the tissues, but has a smaller effect on FA. All of the extracted diffusion
      parameters that are affected by the degree of myelination are affected in a
      diffusion time-dependent fashion, suggesting that the terms apparent anisotropy,
      apparent fractional anisotropy and even apparent root-mean-square displacement
      (rmsD) are more appropriate.

PMID- 24123306
TI  - A computational study on the effect of fracture intrusion distance in three- and
      four-part trochanteric fractures treated with Gamma nail and sliding hip screw.
AB  - Using finite element analysis, the behaviors of the Gamma nail and the sliding
      hip screw (SHS) were compared in an osteoporotic bone model for the fixation of
      three- and four-part trochanteric fractures (31-A2 in the AO classification,
      types IV and V in Evans' classification). The size of the medial fragment was
      varied based on clinical data, and the case of a fractured greater trochanter was
      also considered. Our results showed that for Evans' type V stabilized with a
      Gamma nail and for Evans' types IV and V with the SHS, cancellous bone around the
      lag screw is susceptible to yielding, thus indicating a risk of cut-out. The
      volume of bone susceptible to yielding increases with an increase in size of the
      medial fragment. Conversely, Evans' type IV with a Gamma nail was not predicted
      to cut out. Our findings suggest that future clinical trials investigating
      fixation of unstable proximal fractures should include the size of the medial
      fragment and the integrity of the greater trochanter as covariables and be
      powered to evaluate whether intramedullary devices are superior to SHSs for
      Evans' type IV fractures and inferior/equivalent for type V.

PMID- 24123307
TI  - Health-related quality of life in early Parkinson's disease: the impact of
      nonmotor symptoms.
AB  - Nonmotor symptoms (NMS) are common in patients with established Parkinson's
      disease (PD) and have a major impact upon quality of life. We investigated the
      significance of NMS in relation to health-related quality of life (HRQoL) in
      patients with newly diagnosed PD. Patients and healthy controls were recruited as
      part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal
      Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with
      the Non-Motor Symptom Questionnaire. HRQoL was recorded with the 39-item
      Parkinson's Disease Quality of Life Questionnaire (PDQ-39). Further assessments
      included measures of motor disability, depression, sleep, and cognition. One
      hundred and fifty-eight patients with newly diagnosed PD and 99 controls
      participated in this cross-sectional study. Patients reported greater numbers of
      NMS than controls (mean 8.3 +/- 4.3 versus 2.8 +/- 2.5 symptoms; P < 0.001).
      Patients reported lowest HRQoL in the domains assessing bodily discomfort,
      mobility, and activities of daily living. Motor and nonmotor symptoms impacted
      negatively upon HRQoL scores. Patients with the postural instability and gait
      difficulty motor subtype reported worse HRQoL, compared with those with tremor
      dominant disease. Depression (P < 0.001), incomplete bowel emptying (P < 0.001),
      anxiety (P < 0.001), impaired concentration (P < 0.001), memory complaints (P <
      0.001), and insomnia (P = 0.001) had the greatest negative impact upon HRQoL. NMS
      are common in patients with early PD and represent a significant cause of poorer
      health-related quality of life. Cognitive, neuropsychiatric, and sleep
      disturbances are particularly associated with reduced well-being. Screening and
      management of these symptoms should be prioritized at the time of diagnosis.

PMID- 24123309
TI  - Semiparametric Bayesian joint modeling of a binary and continuous outcome with
      applications in toxicological risk assessment.
AB  - Many dose-response studies collect data on correlated outcomes. For example, in
      developmental toxicity studies, uterine weight and presence of malformed pups are
      measured on the same dam. Joint modeling can result in more efficient inferences
      than independent models for each outcome. Most methods for joint modeling assume
      standard parametric response distributions. However, in toxicity studies, it is
      possible that response distributions vary in location and shape with dose, which
      may not be easily captured by standard models. To address this issue, we propose
      a semiparametric Bayesian joint model for a binary and continuous response. In
      our model, a kernel stick-breaking process prior is assigned to the distribution
      of a random effect shared across outcomes, which allows flexible changes in
      distribution shape with dose shared across outcomes. The model also includes
      outcome-specific fixed effects to allow different location effects. In simulation
      studies, we found that the proposed model provides accurate estimates of
      toxicological risk when the data do not satisfy assumptions of standard
      parametric models. We apply our method to data from a developmental toxicity
      study of ethylene glycol diethyl ether.

PMID- 24123308
TI  - Characterization of human paraoxonase 1 variants suggest that His residues at 115
      and 134 positions are not always needed for the lactonase/arylesterase activities
      of the enzyme.
AB  - Human paraoxonase 1 (h-PON1) hydrolyzes variety of substrates and the hydrolytic
      activities of enzyme can be broadly grouped into three categories; arylesterase,
      phosphotriesterase, and lactonase. Current models of the catalytic mechanism of h
      PON1 suggest that catalytic residues H115 and H134 mediate the lactonase and
      arylesterase activities of the enzyme. H-PON1 is a strong candidate for the
      development of catalytic bioscavenger for organophosphate poisoning in humans.
      Recently, Gupta et al. (Nat. Chem. Biol. 2011. 7, 120) identified amino acid
      substitutions that significantly increased the activity of chimeric-PON1 variant
      (4E9) against some organophosphate nerve agents. In this study we have examined
      the effect of these (L69G/S111T/H115W/H134R/R192K/F222S/T332S) and other
      substitutions (H115W/H134R and H115W/H134R/R192K) on the hydrolytic activities of
      recombinant h-PON1 (rh-PON1) variants. Our results show that the substitutions
      resulted in a significant increase in the organophosphatase activity of all the
      three variants of rh-PON1 enzyme while had a variable effect on the
      lactonase/arylesterase activities. The results suggest that H residues at
      positions 115 and 134 are not always needed for the lactonase/arylesterase
      activities of h-PON1 and force a reconsideration of the current model(s) of the
      catalytic mechanism of h-PON1. 

PMID- 24123310
TI  - Mutated ephrin receptor genes in non-small cell lung carcinoma and their
      occurrence with driver mutations-targeted resequencing study on formalin-fixed,
      paraffin-embedded tumor material of 81 patients.
AB  - Non-small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer.
      The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and
      they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the
      largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far.
      The aim of our study was to investigate novel mutations of Eph genes (EPHA1-8,
      EPHB1-4, EPHB6) and their association with clinically relevant mutations in BRAF,
      EML4-ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53
      in NSCLC patients. Targeted resequencing was conducted on 81 formalin-fixed,
      paraffin-embedded NSCLC tumor specimens. We analyzed missense and nonsense
      mutations harbored in the coding regions of the selected genes. We found 18 novel
      mutations of Ephs in 20% (16 of 81) of the patients. Nearly half of these
      mutations occurred in the protein kinase domain. The mutations were not mutually
      exclusive with other clinically relevant mutations. Our study shows that Ephs are
      frequently mutated in NSCLC patients, and occur together with other known
      mutations relevant to the pathogenicity of NSCLC.

PMID- 24123311
TI  - Soft machines that are resistant to puncture and that self seal.
AB  - A soft machine composed of a composite of elastomer and fibers resists puncture
      from sharp objects, and continues to operate even if punctured. 

PMID- 24123314
TI  - All things to all people? The provision of outreach by community mental health
      teams for older people in England: findings from a national survey.
AB  - OBJECTIVE: The objective of this study is to identify the extent of outreach
      activity community mental health teams (CMHTs) for older people provide to
      mainstream services in light of the recommendations of the National Dementia
      Strategy. In particular, to determine the range of settings in receipt of
      support; to specify the form of this activity; to identify the professionals
      involved; and to explore the factors associated with the provision of such
      support. METHODS: A self-administered postal questionnaire was sent to all CMHTs
      in England. The reported arrangements were categorised and reviewed according to
      a taxonomy of outreach developed from the literature. RESULTS: Three hundred and
      seventy six (88%) of the CMHTs responded. Although nearly all teams undertook
      some outreach work, much of this was informal in nature. Nevertheless, the vast
      majority of teams had some formal outreach arrangements in at least one
      mainstream setting. Just less than three-quarters provided support (most
      typically education) to care homes, approaching half centres to day centres, and
      over a third to primary care practices, social services teams, home care
      providers and general hospitals, respectively. Link workers were the favoured
      means of supporting general hospital staff. Community mental health nurses were
      most commonly involved in providing outreach, and larger teams were more likely
      than smaller teams to have formalised arrangements. A significant minority of
      teams expressed concerns about their capacity to provide effective services.
      CONCLUSIONS: The findings suggest that both more resources and more evidence will
      be needed to meet the National Dementia Strategy's aim of improving care for
      older people with mental health problems in mainstream settings.

PMID- 24123315
TI  - Insight into Lewis acid catalysis with alkaline-earth MOFs: the role of
      polyhedral symmetry distortions.
AB  - We propose a multidisciplinary approach to face the interpretation of
      heterogeneous catalysis with alkaline-earth metal-organic frameworks (MOFs).
      Their oxygen-based polyhedra, which do not exhibit regular geometries, do act as
      very active Lewis acid sites. Four novel alkaline-earth MOFs that belong to three
      different structural types-Mg-AEPF-11, Mg-APF-12, Ca-AEPF-13 and Sr-APF-13-are
      reported, together with their net topologies, and a study of the symmetry
      distortions around the alkaline-earth metal polyhedra by using a continuous shape
      mapping (CShM) description. These MOFs are good catalysts in the selective
      hydrogenation of styrene. Even more, Sr-AEPF-13 shows the best conversions ever
      published with alkaline-earth MOFs for the hydrogenation of activated alkenes
      under mild conditions. A combination of crystallographic and topological analysis
      and theoretical calculations, together with experimental catalytic results, has
      been applied to understand the catalytic activity of these four novel alkaline
      earth MOFs. This work demonstrates that the presence of symmetry-distorted
      alkaline-earth polyhedra gives rise to highly catalytic-active MOFs in the
      hydrogenation of activated alkenes. 

PMID- 24123312
TI  - Epicardial-derived adrenomedullin drives cardiac hyperplasia during
      embryogenesis.
AB  - BACKGROUND: Growth promoting signals from the epicardium are essential for
      driving myocardial proliferation during embryogenesis. In adults, these signals
      become reactivated following injury and promote angiogenesis and myocardial
      repair. Therefore, identification of such paracrine factors could lead to novel
      therapeutic strategies. The multi-functional peptide adrenomedullin (Adm 5 gene,
      AM 5 protein) is required for normal heart development. Moreover, elevated plasma
      AM following myocardial infarction offers beneficial cardioprotection and serves
      as a powerful diagnostic and prognostic indication of disease severity. RESULTS:
      Here, we developed a new model of Adm overexpression by stabilizing the Adm mRNA
      through gene-targeted replacement of the endogenous 30 untranslated region. As
      expected, Admhi/hi mice express three-times more AM than controls in multiple
      tissues, including the heart. Despite normal blood pressures, Admhi/hi mice
      unexpectedly showed significantly enlarged hearts due to increased cardiac
      hyperplasia during development. The targeting vector was designed to allow for
      reversion to wild-type levels by means of Cre-mediated modification. Using this
      approach, we demonstrate that AM derived from the epicardium, but not the
      myocardium or cardiac fibroblast, is responsible for driving cardiomyocyte
      hyperplasia. CONCLUSIONS: AM is produced by the epicardium and drives myocyte
      proliferation during development, thus representing a novel and clinically
      relevant factor potentially related to mechanisms of cardiac repair after injury.

PMID- 24123316
TI  - Development of an MRI phantom for diffusion-weighted imaging with independent
      adjustment of apparent diffusion coefficient values and T2 relaxation times.
AB  - PURPOSE: To design a phantom for diffusion-weighted imaging (DWI) with defined
      apparent diffusion coefficients (ADC) and T2 relaxation times. METHODS: Varying
      concentrations of polyethylene glycol (PEG) were used for the adjustment of
      diffusivity. T2 relaxation times were tuned by adding of the MR contrast agent
      gadobutrol. Relaxation times and apparent diffusion coefficients were quantified
      using a multiecho spin echo sequence and an echo planar imaging (EPI) DWI
      sequence, respectively, on a 3T clinical scanner. RESULTS: Increasing
      concentrations of PEG led to a marked impairment of diffusivity accompanied by
      only moderate changes of T2 relaxation times. Adding gadobutrol to the PEG
      solutions allowed for adjustment of transverse relaxation times to predefined
      values. Thus, a broad range of defined ADC values and T2 relaxation times could
      be accurately achieved in the final phantom. CONCLUSION: The proposed phantom
      allows for standardized in vitro studies of DWI methods and protocols. The
      obtained MR image contrasts are similar to a variety of biological tissues, which
      can contribute to optimization of imaging techniques with respect to specific
      clinical questions. Due to the simplicity of design and the accessibility of the
      contained compounds, this phantom may also serve as a tool for standardization
      and calibration.

PMID- 24123317
TI  - Computational NMR coupling constants: shifting and scaling factors for evaluating
      1JCH.
AB  - Optimized shifting and/or scaling factors for calculating one-bond carbon
      hydrogen spin-spin coupling constants have been determined for 35 combinations of
      representative functionals (PBE, B3LYP, B3P86, B97-2 and M06-L) and basis sets
      (TZVP, HIII-su3, EPR-III, aug-cc-pVTZ-J, ccJ-pVDZ, ccJ-pVTZ, ccJ-pVQZ, pcJ-2 and
      pcJ-3) using 68 organic molecular systems with 88 (1)JCH couplings including
      different types of hybridized carbon atoms. Density functional theory assessment
      for the determination of (1)JCH coupling constants is examined, comparing the
      computed and experimental values. The use of shifting constants for obtaining the
      calculated coupling improves substantially the results, and most models become
      qualitatively similar. Thus, for the whole set of couplings and for all
      approaches excluding those using the M06 functional, the root-mean-square
      deviations lie between 4.7 and 16.4 Hz and are reduced to 4-6.5 Hz when shifting
      constants are considered. Alternatively, when a specific rovibrational
      contribution of 5 Hz is subtracted from the experimental values, good results are
      obtained with PBE, B3P86 and B97-2 functionals in combination with HIII-su3, aug
      cc-pVTZ-J and pcJ-2 basis sets.

PMID- 24123318
TI  - Revisiting the central gland anatomy via MRI: does the central gland extend below
      the level of verumontanum?
AB  - PURPOSE: To determine whether the central gland of the prostate, composed of both
      central and transition zones, extends below the verumontanum in patients over age
      43 based on prostate magnetic resonance imaging (MRI). MATERIALS AND METHODS: In
      all, 82 patients who underwent preoperative, multiparametric endorectal MRI (1.5T
      and 3T) at our institution were included. The central gland was defined as a
      combination of the central zone and transition zone. Two radiologists measured
      central gland extension below verumontanum using axial, coronal, and sagittal T2
      weighted images and coregistration picture archiving and communication system
      software. RESULTS: The final cohort consisted of 63 patients with a mean age of
      60.2 years (standard deviation: 7.1, range: 43-76). The central gland extended
      below the verumontanum in 60/63 (95%) patients. Mean central gland extension
      below the verumontanum was 6.5 mm (standard deviation = 3.7, range: 0, 18). Weak
      (r = 0.35), but significant (P = 0.005) positive correlation was found between
      age and the amount of central gland extension below the verumontanum. CONCLUSION:
      Contrary to McNeal's classical prostatic anatomy teaching, the central gland
      extends below the verumontanum in 95% of men over 43, likely due to deformation
      of the gland by benign prostatic hyperplasia. It is important for pathologists to
      be aware of this observation for accurate characterization of the zonal origin of
      prostate cancer below the level of the verumontanum.

PMID- 24123319
TI  - Functional evaluation of transplanted kidneys using arterial spin labeling MRI.
AB  - PURPOSE: To investigate non-contrast-enhanced arterial spin labeling (ASL) MRI
      for functional assessment of transplanted kidneys at 1.5 Tesla (T) and 3T.
      MATERIALS AND METHODS: This study was approved by the local ethics committee, and
      written informed consent was obtained from all participants. Ninety eight renal
      allograft recipients (mean age, 51.5 +/- 14.6 years) were prospectively included
      in this study. ASL MRI was performed at 1.5T (n = 65) and 3T (n = 33) using a
      single-slice flow-sensitive alternating inversion recovery true-fast imaging with
      steady-state precession (FAIR True-FISP) sequence in the paracoronal plane. ASL
      perfusion was regional analyzed for the renal cortex on parameter maps. ASL was
      compared between patients with good or moderate allograft function (Group a;
      estimated glomerular filtration rate [eGFR] > 30 mL/min/1.73 m(2)) and patients
      with heavily impaired allograft function (Group b; eGFR <= 30 mL/min/1.73 m(2))
      and correlated to renal function as determined by eGFR. RESULTS: ASL perfusion
      and eGFR were comparable at 1.5T (246.9 +/- 66.8 mL/100 g/min and 41.9 +/- 22.7
      mL/min/1.73 m(2)) and 3T (236.5 +/- 102.3 mL/100 g/min and 35.9 +/- 22.9
      mL/min/1.73 m(2)). ASL perfusion was significantly higher in group a (282.7 +/-
      60.8 mL/100 g/min) as compared to group b (178.2 +/- 63.3 mL/100 g/min) (P <
      0.0001). ASL perfusion values exhibited a significant correlation with renal
      function as determined by eGFR (r = 0.59; P < 0.0001). CONCLUSION: Cortical ASL
      perfusion values differ between patients with good or moderate allograft function
      and poor allograft function and correlate significantly with allograft function.
      Our results highlight the potential of ASL MRI for functional evaluation of renal
      allografts.

PMID- 24123320
TI  - Renal cell carcinoma in patients with acquired cystic disease of the kidney:
      assessment using a combination of T2-weighted, diffusion-weighted, and chemical
      shift MRI without the use of contrast material.
AB  - PURPOSE: To evaluate the MRI findings of renal cell carcinoma (RCC), including
      findings on diffusion-weighted images (DWIs) and chemical shift images (CSIs), in
      patients with acquired cystic disease of the kidney (ACDK) in relation to the
      histopathologic findings. MATERIALS AND METHODS: Two radiologists retrospectively
      reviewed the MRI findings of 10 RCCs in seven consecutive patients with ACDK.
      They evaluated the signal intensities (SIs) and signal homogeneity of the lesions
      on T2-weighted images, DWIs, and T1-weighted images. Thereafter, they evaluated
      the cytoplasmic fat in the lesions by CSIs. After image analyses, the MRI
      findings were correlated with the histopathologic findings. RESULTS: The RCCs
      tended to show heterogeneous high SIs on T2-weighted images and DWIs. The high
      SIs on DWIs were mainly attributable to the viable parts, and the heterogeneity
      was due to the various SIs arising from the intratumoral degenerative components.
      Unlike the reported findings for hemorrhagic cysts, the RCCs did not show
      homogeneous high SIs or fluid-iron levels on T1-weighted images. The four
      lesions, in which the presence of cytoplasmic fat was suggested on CSIs, were
      clear cell RCCs. CONCLUSION: The MRI findings, including findings on DWIs and
      CSIs, well reflected the histopathologic findings of RCC in patients with ACDK.

PMID- 24123321
TI  - Symptom burden, loss of dignity, and demoralization in patients with cancer: a
      mediation model.
AB  - BACKGROUND: Demoralization is a syndrome of existential distress that occurs in a
      substantial minority of cancer patients and is associated with a higher number of
      physical problems. Loss of dignity refers to a range of specific existential
      concerns. This study examines whether the association between number of physical
      problems and demoralization is mediated by loss of dignity. METHODS: This cross
      sectional study examined N = 112 inpatients with mixed tumor sites at early and
      advanced disease stages using the following standardized self-report
      questionnaires: Physical problems list of the National Comprehensive Cancer
      Network (NCCN) Distress Thermometer (DT), Patient Dignity Inventory (PDI),
      Demoralization Scale (DS), Patient Health Questionnaire-9 (PHQ-9) and Illness
      Specific Social Support Scale Short Version-8 (ISSS-8). The mediation hypothesis
      was tested by multiple regression analyses controlling for age, gender, curative
      versus palliative treatment phase, and social support. RESULTS: Patients reported
      M =  .7 (SD = 6.0) dignity-related problems; 20% showed moderate to severe
      demoralization. Loss of dignity significantly mediated 81% of the effect of the
      number of physical problems on demoralization (Sobel zs = 4.4, p < .001). Testing
      the reverse direction, we found that demoralization mediated only 53% of the
      association between physical problems and loss of dignity (zs = 3.7, p < .001).
      CONCLUSIONS: By supporting the mediation hypothesis, our results indicate that
      loss of dignity partially explains the association between physical problems and
      demoralization. Early recognition of dignity-related existential concerns and
      interventions to enhance the sense of dignity may prevent demoralization in
      patients with cancer. Results provide a conceptual link between existential
      concerns (loss of dignity) and existential distress (demoralization) as two
      approaches to existential suffering in patients with cancer.

PMID- 24123322
TI  - Comprehensive registration of DNA sequence variants associated with inherited
      retinal diseases in Leiden Open Variation Databases.

PMID- 24123323
TI  - Influence of carbon nanotubes with preloaded and coexisting dissolved organic
      matter on the bioaccumulation of polycyclic aromatic hydrocarbons to Chironomus
      plumosus larvae in sediment.
AB  - The ubiquity of dissolved organic matter (DOM) in an aqueous environment may have
      influence on the carbonaceous material's impact on the bioaccumulation of
      polycyclic aromatic hydrocarbons (PAHs) to benthonic organisms in contaminated
      sediment. In the present study, 1 multiwalled carbon nanotube (MWNT); 2 types of
      DOM (fulvic acid and tannic acid), and 2 PAHs (pyrene and chrysene) were selected
      to study the influence of MWNT with preloaded and coexisting DOM on the
      bioaccumulation of PAHs to Chironomus plumosus larvae in sediment. Moreover, the
      freely dissolved concentrations of PAHs were measured to explore the influence
      mechanisms. The results showed that despite the presence or absence of preloaded
      or coexisting DOM, the presence of 1% MWNT in sediments suppressed the biota
      sediment accumulation factor (BSAF) and elevated the water-based bioaccumulation
      factor (BAF) of PAHs. However, the BSAF and BAF values generally decreased with
      the increase of 2 forms of both DOM; this was caused by the combined impact of
      DOM and MWNT on the freely dissolved concentrations of PAHs and the ingestion
      behavior of benthic organisms.

PMID- 24123324
TI  - Characterization of the elusive rhodizonate ring-contraction decarbonylation
      C5O4(OH)CO2Me2- intermediate to croconate.

PMID- 24123325
TI  - Nearly degenerate isomers of C(BH)2: cumulene, carbene, or carbone?
AB  - The ground electronic state of C(BH)2 exhibits both a linear minimum and a
      peculiar angle-deformation isomer with a central B-C-B angle near 90 degrees .
      Definitive computations on these species and the intervening transition state
      have been executed by means of coupled-cluster theory including single and double
      excitations (CCSD), perturbative triples (CCSD(T)), and full triples with
      perturbative quadruples (CCSDT(Q)), in concert with series of correlation
      consistent basis sets (cc-pVXZ, X=D, T, Q, 5, 6; cc-pCVXZ, X=T, Q). Final
      energies were pinpointed by focal-point analyses (FPA) targeting the complete
      basis-set limit of CCSDT(Q) theory with auxiliary core correlation, relativistic,
      and non-Born-Oppenheimer corrections. Isomerization of the linear species to the
      bent form has a minuscule FPA reaction energy of 0.02 kcal mol(-1) and a
      corresponding barrier of only 1.89 kcal mol(-1). Quantum tunneling computations
      reveal interconversion of the two isomers on a timescale much less than 1 s even
      at 0 K. Highly accurate CCSD(T)/cc-pVTZ and composite c~CCSDT(Q)/cc-pCVQZ
      anharmonic vibrational frequencies confirm matrix-isolation infrared bands
      previously assigned to linear C(BH)2 and provide excellent predictions for the
      heretofore unobserved bent isomer. Chemical bonding in the C(BH)2 species was
      exhaustively investigated by the atoms-in-molecules (AIM) approach, molecular
      orbital plots, various population analyses, local mode vibrations and force
      constants, unified reaction valley analysis (URVA), and other methods. Linear
      C(BH)2 is a cumulene, whereas bent C(BH)2 is best characterized as a carbene with
      little carbone character. Weak B-B attraction is clearly present in the unusual
      bent isomer, but its strength is insufficient to form a CB2 ring with a genuine
      boron-boron bond and attendant AIM bond path.

PMID- 24123326
TI  - Heat shock improves Sca-1+ stem cell survival and directs ischemic cardiomyocytes
      toward a prosurvival phenotype via exosomal transfer: a critical role for
      HSF1/miR-34a/HSP70 pathway.
AB  - Stem cell-based therapy is a promising intervention for ischemic heart diseases.
      However, the functional integrity of stem cells is impaired in an ischemic
      environment. Here, we report a novel finding that heat shock significantly
      improves Sca-1(+) stem cell survival in an ischemic environment by the regulation
      of the triangle: heat shock factor 1 (HSF1), HSF1/miR-34a, and heat shock protein
      70 (HSP70). Initially we prove that HSP70 is the key chaperone-mediating
      cytoprotective effect of heat shock in Sca-1(+) cells and then we establish miR
      34a as a direct repressor of HSP70. We found that miR-34a was downregulated in
      heat shocked Sca-11 stem cells (HSSca-11 cells) [corrected]. Intriguingly, we
      demonstrate that the downregulation of miR-34a is attributed to HSF1-mediated
      epigenetic repression through histone H3 Lys27 trimethylation (H3K27me3) on miR
      34a promoter. Moreover, we show that heat shock induces exosomal transfer of HSF1
      from Sca-1(+) cells, which directs ischemic cardiomyocytes toward a prosurvival
      phenotype by epigenetic repression of miR-34a. In addition, our in vivo study
      demonstrates that transplantation of (HS) Sca-1(+) cells significantly reduces
      apoptosis, attenuates fibrosis, and improves global heart functions in ischemic
      myocardium. Hence, our study provides not only novel insights into the effects of
      heat shock on stem cell survival and paracrine behavior but also may have
      therapeutic values for stem cell therapy in ischemic heart diseases.

PMID- 24123327
TI  - Future of brain stimulation: new targets, new indications, new technology.
AB  - In the last quarter of a century, DBS has become an established neurosurgical
      treatment for Parkinson's disease (PD), dystonia, and tremors. Improved
      understanding of brain circuitries and their involvement in various neurological
      and psychiatric illnesses, coupled with the safety of DBS and its exquisite role
      as a tool for ethical study of the human brain, have unlocked new opportunities
      for this technology, both for future therapies and in research. Serendipitous
      discoveries and advances in structural and functional imaging are providing
      abundant "new" brain targets for an ever-increasing number of pathologies,
      leading to investigations of DBS in diverse neurological, psychiatric,
      behavioral, and cognitive conditions. Trials and "proof of concept" studies of
      DBS are underway in pain, epilepsy, tinnitus, OCD, depression, and Gilles de la
      Tourette syndrome, as well as in eating disorders, addiction, cognitive decline,
      consciousness, and autonomic states. In parallel, ongoing technological
      development will provide pulse generators with longer battery longevity,
      segmental electrode designs allowing a current steering, and the possibility to
      deliver "on-demand" stimulation based on closed-loop concepts. The future of
      brain stimulation is certainly promising, especially for movement disorders-that
      will remain the main indication for DBS for the foreseeable future-and probably
      for some psychiatric disorders. However, brain stimulation as a technique may be
      at risk of gliding down a slippery slope: Some reports indicate a disturbing
      trend with suggestions that future DBS may be proposed for enhancement of memory
      in healthy people, or as a tool for "treatment" of "antisocial behavior" and for
      improving "morality."

PMID- 24123329
TI  - Prognosis of delirium in hospitalized elderly: worse than we thought.
AB  - BACKGROUND: Despite treatment of the associated condition, delirious persons do
      not always recover for unknown reasons. We sought to determine early prognostic
      indicators of poor recovery following an episode of delirium in older medical in
      patients. METHODS: Between October 2009 and July 2011, consecutively admitted
      older (>=70 years old) medical in-patients at the London Health Sciences Centre
      (Ontario) were screened for delirium. Delirious patients were followed. The
      primary outcome was poor recovery, in delirious patients, defined by death, long
      term institutionalization, or functional decline (decreased activities of daily
      living), at discharge or 3 months after discharge, elicited from the medical
      chart or post-discharge caregiver telephone interviews. RESULTS: One thousand two
      hundred thirty-five in-patients (mean age 82.6 years, 42% men) were screened,
      delirium occurred in 355 (29%). Follow-up data was known on 342 (96%), and 237
      (69%) had poor recovery: 55 died (54 in hospital and one after discharge), 136
      were permanently institutionalized (86 directly from hospital and 50 after
      discharge), and 46 had functional decline (at a median of 103 days after
      discharge). Poor recovery was associated in the derivation sample with advanced
      age, lower baseline function, hypoxia, higher delirium severity scores, and acute
      renal failure; this was predictive of poor recovery in the validation sample
      (receiver operating characteristic area 0.68, 95% confidence interval: 0.57
      0.79); however, even individuals with "low" risk had high (50%) poor recovery
      rates. INTERPRETATION: Poor recovery after delirium is common and associated with
      certain characteristics. However, even "lower risk" delirious individuals do
      poorly. More research is needed to understand prognostic factors in delirium.

PMID- 24123330
TI  - ZnSe etching of Zn-rich Cu2ZnSnSe4: an oxidation route for improved solar-cell
      efficiency.
AB  - Cu2ZnSnSe4 kesterite compounds are some of the most promising materials for low
      cost thin-film photovoltaics. However, the synthesis of absorbers for high
      performing devices is still a complex issue. So far, the best devices rely on
      absorbers grown in a Zn-rich and Cu-poor environment. These off-stoichiometric
      conditions favor the presence of a ZnSe secondary phase, which has been proved to
      be highly detrimental for device performance. Therefore, an effective method for
      the selective removal of this phase is important. Previous attempts to remove
      this phase by using acidic etching or highly toxic organic compounds have been
      reported but so far with moderate impact on device performance. Herein, a new
      oxidizing route to ensure efficient removal of ZnSe is presented based on
      treatment with a mixture of an oxidizing agent and a mineral acid followed by
      treatment in an aqueous Na2S solution. Three different oxidizing agents were
      tested: H2O2, KMnO4, and K2Cr2O7, combined with different concentrations of
      H2SO4. With all of these agents Se(2-) from the ZnSe surface phase is selectively
      oxidized to Se(0), forming an elemental Se phase, which is removed with the
      subsequent etching in Na2S. Using KMnO4 in a H2SO4-based medium, a large
      improvement on the conversion efficiency of the devices is observed, related to
      an improvement of all the optoelectronic parameters of the cells. Improvement of
      short-circuit current density (J(sc)) and series resistance is directly related
      to the selective etching of the ZnSe surface phase, which has a demonstrated
      current-blocking effect. In addition, a significant improvement of open-circuit
      voltage (V(oc)), shunt resistance (R(sh)), and fill factor (FF) are attributed to
      a passivation effect of the kesterite absorber surface resulting from the
      chemical processes, an effect that likely leads to a reduction of nonradiative
      recombination states density and a subsequent improvement of the p-n junction.

PMID- 24123328
TI  - Glutamate and glutamine: a review of in vivo MRS in the human brain.
AB  - Our understanding of the roles that the amino acids glutamate (Glu) and glutamine
      (Gln) play in the mammalian central nervous system has increased rapidly in
      recent times. Many conditions are known to exhibit a disturbance in Glu-Gln
      equilibrium, and the exact relationships between these changed conditions and
      these amino acids are not fully understood. This has led to increased interest in
      Glu/Gln quantitation in the human brain in an array of conditions (e.g. mental
      illness, tumor, neuro-degeneration) as well as in normal brain function.
      Accordingly, this review has been undertaken to describe the increasing number of
      in vivo techniques available to study Glu and Gln separately, or pooled as 'Glx'.
      The present MRS methods used to assess Glu and Gln vary in approach, complexity,
      and outcome, thus the focus of this review is on a description of MRS acquisition
      approaches, and an indication of relative utility of each technique rather than
      brain pathologies associated with Glu and/or Gln perturbation. Consequently, this
      review focuses particularly on (1) one-dimensional (1)H MRS, (2) two-dimensional
      (1)H MRS, and (3) one-dimensional (13)C MRS techniques.

PMID- 24123331
TI  - Comparing the effect of equiaxial cyclic mechanical stimulation on GATA4
      expression in adipose-derived and bone marrow-derived mesenchymal stem cells.
AB  - Myocardium is prone to mechanical stimuli among which pulsatile blood flow exerts
      both radial and longitudinal strains on the heart. Recent studies have shown that
      mechanical stimulation can notably influence regeneration of cardiac muscle
      cells. GATA4 is a cardiac-specific transcription factor that plays an important
      role in late embryonic heart development. Our study aimed at investigating the
      effect of equiaxial cyclic strain on GATA4 expression in adipose-derived (ASCs)
      and bone marrow-derived (BMSCs) mesenchymal stem cells. For this reason, both
      ASCs and BMSCs were studied in four distinct groups of chemical, mechanical,
      mechano-chemical and negative control. According to this categorisation, the
      cells were exposed to cyclic mechanical loading and/or 5-azacytidine as the
      chemical factor. The level of GATA4 expression was then quantified using real
      time PCR method on the first, fourth and seventh days. The results show that: (1)
      equiaxial cyclic stimulation of mesenchymal stem cells could promote GATA4
      expression from the early days of induction and as it went on, its combination
      with chemical factor elevated expression; (2) cyclic strain could accelerate
      GATA4 expression compared to the chemical factor; (3) in this regard, these
      results indicate a higher capacity of ASCs than BMSCs to express GATA4. 

PMID- 24123335
TI  - Gadolinium-based contrast agents: what does "single-dose" mean anymore?

PMID- 24123337
TI  - In vivo detection of citrate in brain tumors by 1H magnetic resonance
      spectroscopy at 3T.
AB  - PURPOSE: To test whether citrate is elevated in adult patients with gliomas using
      (1)H magnetic resonance spectroscopy (MRS) at 3T in vivo. METHODS: Thirty-four
      adult patients were enrolled in the study, including six subjects with
      glioblastomas, eight subjects with astrocytomas (World Health Organization grade
      3, n = 5; grade 2, n = 3), and 20 subjects with oligodendrogliomas (grade 3, n =
      5; grade 2, n = 15). Five healthy volunteers were studied for baseline citrate
      data. Single-voxel localized spectra were collected with point-resolved
      spectroscopy (PRESS) echo times of 35 and 97 ms and were analyzed with LCModel
      software using numerically calculated basis spectra that included the effects of
      the PRESS radiofrequency and gradient pulses. RESULTS: Citrate was not measurable
      by MRS in healthy brain but was detected in tumor patients at both echo times.
      The citrate concentration was estimated to be as high as 1.8 mM with reference to
      water at 42 M, with Cramer-Rao lower bounds (CRLB) as low as 5%. The mean citrate
      level was 0.7 +/- 0.4 mM (mean +/- SD, n = 32) with a median CRLB of ~12%. No
      correlation was identified between citrate concentration and tumor grade or
      histological type. CONCLUSION: Citrate was increased in the majority of gliomas
      in adult patients. The elevated citrate in our data indicates an altered
      metabolic state of tumor relative to healthy brain.

PMID- 24123338
TI  - 1H and 13C NMR assignments of bioactive indeno[1,2-b]indole-10-one derivatives.
AB  - The complete (1)H and (13)C assignments of eight bioactive indeno[1,2-b]indole-10
      one derivatives were accomplished by the combined use of one-dimensional and two
      dimensional NMR experiments.

PMID- 24123339
TI  - Optimism, social support, and mental health outcomes in patients with advanced
      cancer.
AB  - OBJECTIVE: Optimism and social support serve as protective factors against
      distress in medically ill patients. Very few studies have specifically explored
      the ways in which these variables interact to impact quality of life (QOL),
      particularly among patients with advanced cancer. The present study examined the
      role of optimism as a moderator of the relationship between social support and
      anxiety, depression, hopelessness, and QOL among patients with advanced cancer.
      METHODS: Participants (N = 168) completed self-report assessments of
      psychosocial, spiritual, and physical well-being, including social support,
      optimism, hopelessness, depressive and anxious symptoms, and QOL. Hierarchical
      multiple regression analyses were conducted to determine the extent to which
      social support and optimism were associated with depressive and anxious
      symptomatology, hopelessness and QOL, and the potential role of optimism as a
      moderator of the relationship between social support and these variables.
      RESULTS: Higher levels of optimism were significantly associated with fewer
      anxious and depressive symptoms, less hopelessness, and better QOL. Higher levels
      of perceived social support were also significantly associated with better QOL.
      Additionally, optimism moderated the relationship between social support and
      anxiety, such that there was a strong negative association between social support
      and anxiety for participants with low optimism. CONCLUSIONS: This study
      highlights the importance of optimism and social support in the QOL of patients
      with advanced cancer. As such, interventions that attend to patients'
      expectations for positive experiences and the expansion of social support should
      be the focus of future clinical and research endeavors.

PMID- 24123341
TI  - The receptor-like kinases GSO1 and GSO2 together regulate root growth in
      Arabidopsis through control of cell division and cell fate specification.
AB  - BACKGROUND: The root apical meristem of Arabidopsis is established post
      embryonically as the main source of root cells, and its activity is maintained by
      complex bidirectional signaling between stem cells and mature cells. The receptor
      like kinases GASSHO1 (GSO1) and GSO2 have been shown to regulate aerial epidermal
      function and seedling growth in Arabidopsis. RESULTS: Here we show that gso1;
      gso2 seedlings also have root growth and patterning defects. Analyses of mutant
      root morphology indicate abnormal numbers of cells in longitudinal files and
      radial cell layers, as well as aberrant stem cell division planes. gso1; gso2
      double mutants misexpress markers for stem cells and differentiated root cell
      types. In addition, gso1; gso2 root growth defects, but not marker missexpression
      or patterning phenotypes, are rescued by growth on media containing metabolizable
      sugars. CONCLUSIONS: We conclude that GSO1 and GSO2 function together in
      intercellular signaling to positively regulate cell proliferation,
      differentiation of root cell types, and stem cell identity. In addition, GSO1 and
      GSO2 control seedling root growth by modulating sucrose response after
      germination.

PMID- 24123340
TI  - An NTD-associated polymorphism in the 3' UTR of MTHFD1L can affect disease risk
      by altering miRNA binding.
AB  - Maternal folate levels and polymorphisms in folate-related genes are known risk
      factors for neural tube defects (NTDs). SNPs in the mitochondrial folate gene
      MTHFD1L are associated with the risk of NTDs. We investigated whether different
      alleles of SNP rs7646 in the 3' UTR of MTHFD1L can be differentially regulated by
      microRNAs affecting MTHFD1L expression. We previously reported that miR-9 targets
      MTHFD1L and now we identify miR-197 as an additional miRNA regulator. Both of
      these miRNAs have predicted binding sites in the MTHFD1L 3' UTR in the region
      containing SNP rs7646. We have determined whether the alleles of SNP rs7646 (A/G)
      and miRNA expression levels affect miRNA binding preferences for the MTHFD1L 3'
      UTR and consequently MTHFD1L expression. Our results indicate that miR-9 and miR
      197 specifically downregulate MTHFD1L levels in HEK293 and MCF-7 cells and that
      SNPrs7646 significantly affects miR-197 binding affinity to the MTHFD1L 3' UTR,
      causing more efficient posttranscriptional gene repression in the presence of the
      allele that is associated with increased risk of NTDs. These results reveal that
      the association of SNP rs7646 and NTD risk involves differences in microRNA
      regulation and, highlights the importance of genotype-dependent differential
      microRNA regulation in relation to human disease risk. 

PMID- 24123342
TI  - Pulmonary 3 T MRI with ultrashort TEs: influence of ultrashort echo time interval
      on pulmonary functional and clinical stage assessments of smokers.
AB  - PURPOSE: To assess the influence of ultrashort TE (UTE) intervals on pulmonary
      magnetic resonance imaging (MRI) with UTEs (UTE-MRI) for pulmonary functional
      loss assessment and clinical stage classification of smokers. MATERIALS AND
      METHODS: A total 60 consecutive smokers (43 men and 17 women; mean age 70 years)
      with and without COPD underwent thin-section multidetector row computed
      tomography (MDCT), UTE-MRI, and pulmonary functional measurements. For each
      smoker, UTE-MRI was performed with three different UTE intervals (UTE-MRI A: 0.5
      msec, UTE-MRI B: 1.0 msec, UTE-MRI C: 1.5 msec). By using the GOLD guidelines,
      the subjects were classified as: "smokers without COPD," "mild COPD," "moderate
      COPD," and "severe or very severe COPD." Then the mean T2* value from each UTE
      MRI and CT-based functional lung volume (FLV) were correlated with pulmonary
      function test. Finally, Fisher's PLSD test was used to evaluate differences in
      each index among the four clinical stages. RESULTS: Each index correlated
      significantly with pulmonary function test results (P < 0.05). CT-based FLV and
      mean T2* values obtained from UTE-MRI A and B showed significant differences
      among all groups except between "smokers without COPD" and "mild COPD" groups (P
      < 0.05). CONCLUSION: UTE-MRI has a potential for management of smokers and the
      UTE interval is suggested as an important parameter in this setting.

PMID- 24123343
TI  - 25th anniversary article: Chemically modified/doped carbon nanotubes & graphene
      for optimized nanostructures & nanodevices.
AB  - Outstanding pristine properties of carbon nanotubes and graphene have limited the
      scope for real-life applications without precise controllability of the material
      structures and properties. This invited article to celebrate the 25th anniversary
      of Advanced Materials reviews the current research status in the chemical
      modification/doping of carbon nanotubes and graphene and their relevant
      applications with optimized structures and properties. A broad aspect of specific
      correlations between chemical modification/doping schemes of the graphitic
      carbons with their novel tunable material properties is summarized. An overview
      of the practical benefits from chemical modification/doping, including the
      controllability of electronic energy level, charge carrier density, surface
      energy and surface reactivity for diverse advanced applications is presented,
      namely flexible electronics/optoelectronics, energy conversion/storage,
      nanocomposites, and environmental remediation, with a particular emphasis on
      their optimized interfacial structures and properties. Future research direction
      is also proposed to surpass existing technological bottlenecks and realize
      idealized graphitic carbon applications.

PMID- 24123344
TI  - Implications of high antifungal susceptibility on Schizophyllum commune
      associated allergy in clinical practice.

PMID- 24123345
TI  - Reply to "implications of high antifungal susceptibility on Schizophyllum commune
      associated allergy in clinical practice".

PMID- 24123346
TI  - Chloroquine, an antifungal but also a fertility drug.

PMID- 24123347
TI  - Reply to "chloroquine, an antifungal but also a fertility drug".

PMID- 24123350
TI  - Biomagnification of mercury through a subtropical coastal food web off southwest
      Florida.
AB  - Total mercury and stable isotopes of nitrogen (delta(15) N) were measured in
      samples from 57 species of invertebrates (17 species) and finfish (40 species)
      from the coastal waters off southwest Florida, USA, to evaluate the
      biomagnification of mercury through the food web. Mercury concentrations (wet wt)
      and delta(15) N values were highly variable among species, ranging from 0.004
      mg/kg in an unidentified species of brittlestar (class Ophiuroidea) to 2.839 +/-
      1.39 mg/kg in king mackerel (Scomberomorus cavalla) and from 4.670/00 in a
      Florida fighting conch (Strombus alatus) to 13.680/00 in crevalle jack (Caranx
      hippos). In general, observed Hg levels were in the upper range of levels
      previously reported for other Gulf populations. Species means of log-transformed
      Hg concentrations were positively correlated with delta(15) N (p < 0.001, r(2)  =
      0.66) and had a slope of 0.21. A trophic magnification factor of 5.05 was
      calculated from the relationship between log-transformed mean Hg concentrations
      and trophic level (calculated from delta(15) N), indicating that Hg increased by
      a factor of 5 with each increase in trophic level. The log10 [Hg]-delta(15) N
      slope and trophic magnification factor were also in the upper range of values
      reported from other regions and ecosystems.

PMID- 24123351
TI  - Extraction yields and anti-oxidant activity of proanthocyanidins from different
      parts of grape pomace: effect of mechanical treatments.
AB  - INTRODUCTION: White grape pomace is not subject to maceration, keeping nearly all
      polyphenols of grapes, so they represent important sources of bioactive compounds
      such as proanthocyanidins. Preparation of plant polyphenol extracts is usually
      performed using raw material powder. However, the fine particles make the further
      extraction procedure steps more difficult. OBJECTIVE: To study the effect of
      mechanical treatments on extraction yields and anti-oxidant activity from
      different parts of white grape pomace. METHODS: Skins, stems and seeds were
      isolated from the pomace of white winemaking process. Sequential solvent
      extraction of polyphenols, first using 80% methanol in water followed by 75%
      acetone in water, was carried out on both entire and milled (< 1 mm) grape
      solids; extraction on seed polyphenols was also performed in its squashed form.
      The phenolic content of each extract was verified by spectrometric and HPLC
      methods and its anti-oxidant activity was evaluated by the 1,1-diphenyl-2
      picrylhydrazyl test. RESULTS: More total polyphenols can be extracted from each
      milled tissue than from its entire form. Seeds present the highest total phenol,
      oligomeric and polymeric proanthocyanidin content, and similar extraction yield
      was found between milled and squashed tissues. The HPLC analysis showed no
      difference in extraction yield of low-molecular-weight proanthocyanidins between
      milled and entire stems. Anti-oxidant activity showed a positive correlation with
      total phenol content, galloyled oligomers and polymeric proanthocyanidins.
      CONCLUSION: The use of entire stems and squashed seeds for solvent extraction of
      polyphenols makes manipulation simpler and more cost-efficient, providing similar
      extraction yields to using their powdery forms.

PMID- 24123352
TI  - Development of a novel multifunctional n,p ligand for highly enantioselective
      palladium-catalyzed asymmetric allylic etherification of alcohols and silanols.
AB  - CycloN2P2-Phos! The use of the multidentate phosphine, CycloN2P2-Phos, which
      contains four heteroatoms (two nitrogen and two phosphorus atoms), in the
      palladium-catalyzed asymmetric allylic etherification (AAE) of alcohols and
      silanols leads to excellent levels of enantioselectivity (up to 99 % ee). 

PMID- 24123353
TI  - A selective sigma-2 receptor ligand antagonizes cocaine-induced hyperlocomotion
      in mice.
AB  - Cocaine functions, in part, through agonist actions at sigma-1 (sigma1 )
      receptors, while roles played by sigma-2 (sigma2 ) receptors are less
      established. Attempts to discriminate sigma2 receptor-mediated effects of cocaine
      in locomotor hyperactivity assays have been hampered by the lack of potent and
      selective antagonists. Certain tetrahydroisoquinolinyl benzamides display high
      sigma2 receptor affinity, and excellent selectivity for binding to sigma2 over
      sigma1 receptors. The behavioral properties of this structural class of sigma
      ligands have not yet been investigated. The present study evaluated 5-bromo-N-[4
      (6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide,
      1, a ligand shown by others to bind preferentially to sigma2 over sigma1
      receptors, as well as dopamine D2 and D3 sites. First, we determined binding to
      monoamine transporters and opioid receptors, and noted 57-fold selectivity for
      sigma2 receptors over the serotonin transporter, and >800-fold selectivity for
      sigma2 receptors over the other sites tested. We then examined 1 in locomotor
      activity studies using male CD-1(r) mice, and saw no alteration of basal activity
      at doses up to 31.6 umol/kg. Cocaine produced a fivefold increase in locomotor
      activity, which was attenuated by 66% upon pretreatment of mice with 1 at 31.6
      umol/kg. In vivo radioligand binding studies also were performed, and showed no
      occupancy of sigma1 receptors or the dopamine transporter by 1, or its possible
      metabolites, at the 31.6 umol/kg dose. Thus, ligand 1 profiles behaviorally as a
      sigma2 receptor-selective antagonist that is able to counteract cocaine's motor
      stimulatory effects.

PMID- 24123354
TI  - Recurrent pre-existing and acquired DNA copy number alterations, including focal
      TERT gains, in neuroblastoma central nervous system metastases.
AB  - Stage 4 neuroblastomas have a high rate of local and metastatic relapse and
      associated disease mortality. The central nervous system (CNS) is currently one
      of the most common isolated relapse sites, yet the genomic alterations that
      contribute to these metastases are unknown. This study sought to identify
      recurrent DNA copy number alterations (CNAs) and target genes relating to
      neuroblastoma CNS metastases by studying 19 pre-CNS primary tumors and 27 CNS
      metastases, including 12 matched pairs. SNP microarray analyses revealed that
      MYCN amplified (MYCNA) tumors had recurrent CNAs different from non-MYCNA
      cohorts. Several CNAs known to be prevalent among primary neuroblastomas occurred
      more frequently in CNS metastases, including 4p-, 7q+, 12q+, and 19q- in non
      MYCNA metastases, and 9p- and 14q- irrespective of MYCNA status. In addition,
      novel CNS metastases-related CNAs included 18q22.1 gains in non-MYCNA pre-CNS
      primaries and 5p15.33 gains and 15q26.1->tel losses in non-MYCNA CNS metastases.
      Based on minimal common regions, gene expression, and biological properties, TERT
      (5p), NR2F2 (15q), ALDH1A3 (15q), CDKN2A (9p), and possibly CDH7 and CDH19 (18q)
      were candidate genes associated with the CNS metastatic process. Notably, the
      5p15 minimal common region contained only TERT, and non-MYCNA CNS metastases with
      focal 5p15 gains had increased TERT expression, similar to MYCNA tumors. These
      findings suggest that a specific genomic lesion (18q22.1 gain) predisposes to CNS
      metastases and that distinct lesions are recurrently acquired during metastatic
      progression. Among the acquired lesions, increased TERT copy number and
      expression appears likely to function in lieu of MYCNA to promote CNS metastasis.

PMID- 24123355
TI  - Dose response of the intravascular contrast agent gadofosveset trisodium in MR
      perfusion imaging of the myocardium using semiquantitative evaluation.
AB  - PURPOSE: To evaluate appropriate injection protocols for gadofosveset at 1.5 and
      3 T magnetic resonance imaging (MRI) for semiquantitative myocardial perfusion
      analysis. MATERIALS AND METHODS: Eighteen young healthy volunteers were subjected
      to first-pass perfusion cardiac scans at 1.5 and 3 T MRI using three different
      injection protocols for gadofosveset (0.00375, 0.0075, and 0.0150 mmol/kg
      bodyweight) and two perfusions. At both field strengths a T1-weighted saturation
      recovery turboFLASH sequence with parallel imaging was employed. Peak signal-to
      noise ratio (SNR), maximum contrast enhancement ratio (CER), peak-baseline
      difference, and upslope values were assessed. Moreover, sectors with dark banding
      artifacts were evaluated. RESULTS: Significant differences of the upslope values
      for first compared to second perfusion could be observed for the medium- and high
      dose groups at 1.5 T (P < 0.01), but not at 3 T. Sectors with dark banding
      artifacts during first perfusion occurred significantly more often at the highest
      dose of gadofosveset compared to the lowest dose at 1.5 T (P = 0.04) and 3 T (P <
      0.01). CONCLUSION: The best injection protocol for semiquantitative perfusion
      analysis at 1.5 T is 0.00375 mmol/kg, as higher doses lead to lower upslope
      values during the second perfusion. At 3 T 0.0075 mmol/kg should be used to avoid
      dark banding artifacts.

PMID- 24123356
TI  - Heterogeneous Cu(II) -catalysed solvent-controlled selective N-arylation of
      cyclic amides and amines with bromo-iodoarenes.
AB  - A selective N-arylation of cyclic amides and amines in DMF and water,
      respectively, catalysed by Cu(II) /Al2 O3 has been achieved. This protocol has
      been employed for the synthesis of a library of arenes bearing a cyclic amide and
      an amine moiety at two ends, including a few scaffolds of therapeutic importance.
      The mechanism has been established based on detailed electron paramagnetic
      resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse
      reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry
      (ICP-MS) studies of the catalyst at different stages of the reaction. The Cu(II)
      /Al2 O3 catalyst was recovered and recycled for subsequent reactions. 

PMID- 24123357
TI  - The nuances of cognition and depression in older adults: the need for a
      comprehensive assessment.
AB  - OBJECTIVES: This study aimed to examine the confluence of depression, cognitive
      impairment, and vascular risk factors in older individuals. METHODS: The study
      uses baseline data from the National Alzheimer's Coordinating Center. Data were
      collected across Alzheimer's Disease Centers in the USA. The sample included
      12,634 individuals (cognitive intact = 8022; amnestic mild cognitive impairment
      [aMCI] = 3652; nonamnestic MCI [nonaMCI] = 960). The Geriatric Depression Scale
      assessed depression; the Trail Making Test assessed executive function. RESULTS:
      The proportion of participants with depression was higher in the aMCI (18%) and
      nonaMCI group (21%) as compared with that in the cognitively intact group (8%);
      there was no difference in rates of depression between aMCI and nonaMCI groups.
      The proportion of participants with executive dysfunction differed between
      nondepressed and depressed individuals for the cognitively intact (8% vs. 12%)
      and aMCI groups (28% vs. 35%), but not for the nonaMCI group (37% vs. 41%). Nine
      percent of the cognitively intact group had executive dysfunction compared with
      31% of the aMCI group and 40% of the nonaMCI group. The proportion of
      participants with hypertension was greater in individuals with executive
      dysfunction compared with those with no executive deficits; the presence of
      hypertension was not associated with depression severity. CONCLUSIONS: The
      confluence of vascular risk factors, episodic memory impairment, and depression
      and executive dysfunction highlights the need for comprehensive assessment of
      depressed older adults that can aid clinicians in the formulation of treatment
      planning and inform clinicians and researchers about long-term prognosis.

PMID- 24123358
TI  - Alcohol challenge and sensitivity to change of the Essential Tremor Rating
      Assessment Scale.
AB  - BACKGROUND: The ability of the Essential Tremor (ET) Rating Assessment Scale
      (TETRAS) to detect changes in tremor severity is unknown. METHODS: Fifteen adult
      ET patients received a single oral ethanol dose calculated to reach 0.05 g/dL
      breath alcohol content (brAC). Effects were investigated independently with
      accelerometry and TETRAS. RESULTS: Accelerometry data were log-transformed and a
      cumulative score logACC(R+L) was calculated. Correlation between logACC(R+L) and
      TETRAS was significant. TETRAS and accelerometry showed a significant effect of
      time point using repeated-measures analysis of variance. The difference between
      baseline and each of the following six time points as well as the correlation of
      TETRAS with brAC were significant. The calculated minimum detectable change of
      TETRAS was 8.9% and the effect size was d = 4.75 (95% confidence interval: 3.60
      5.90). CONCLUSION: We demonstrated sensitivity to change of the TETRAS
      performance scale after a therapeutic intervention, which further establishes its
      potential for use in both clinical and research settings.

PMID- 24123359
TI  - Galactose-functionalized cationic polycarbonate diblock copolymer for targeted
      gene delivery to hepatocytes.
AB  - To mediate selective gene delivery to hepatocytes via the asialoglycoprotein
      receptors (ASGP-Rs), we designed and synthesized well-defined and narrowly
      dispersed galactose- and glucose-functionalized cationic polycarbonate diblock
      copolymers (designated as Gal-APC and Glu-APC, respectively) using
      organocatalytic ring-opening polymerization of functionalized carbonate monomers,
      with a subsequent quaternization step using bis-tertiary amines to confer
      quaternary and tertiary amines for DNA binding and endosomal buffering,
      respectively. The sugar-functionalized diblock copolymers effectively bound and
      condensed DNA to form positively charged nanoparticles (<100 nm in diameter and
      ~30 mV zeta-potential) that were stable under high physiological salt conditions.
      In comparison to the control Glu-APC/DNA complexes, Gal-APC/DNA complexes
      mediated significantly higher gene expression in ASGP-R positive HepG2 cells with
      no significant difference observed in ASGP-R negative HeLa cells. The co
      incubation of Gal-APC/DNA complexes with a natural ASGP-R ligand effectively led
      to a decrease in gene expression, hence providing evidence for the ASGP-R
      mediated endocytosis of the polyplexes. Importantly, the Gal-APC/DNA complexes
      induced minimal cytotoxicities in HepG2 cells at the N/P ratios tested. Taken
      together, the galactose-functionalized cationic polycarbonate diblock copolymer
      has potential for use as a non-viral gene vector for the targeted delivery of
      therapeutic genes to hepatocytes in the treatment of liver diseases. 

PMID- 24123361
TI  - Grignard reagent/CuI/LiCl-mediated stereoselective cascade addition/cyclization
      of diynes: a novel pathway for the construction of 1-methyleneindene derivatives.
AB  - Diynes containing a cyclopropane group smoothly undergo a novel intramolecular
      and stereoselective cascade addition/cyclization reaction to produce the
      corresponding 1-methyleneindene derivatives in moderate to good yields. This
      interesting transformation is mediated by Grignard reagent/CuI with LiCl as an
      additive under mild conditions. The obtained product can easily be further
      functionalized through cyclopropyl ring opening. A plausible reaction mechanism
      has also been presented on the basis of deuterium labeling and control
      experiments. 

PMID- 24123360
TI  - The transition from stem cell to progenitor spermatogonia and male fertility
      requires the SHP2 protein tyrosine phosphatase.
AB  - SHP2 is a widely expressed protein tyrosine phosphatase required for signal
      transduction from multiple cell surface receptors. Gain and loss of function SHP2
      mutations in humans are known to cause Noonan and LEOPARD syndromes,
      respectively, that are characterized by numerous pathological conditions
      including male infertility. Using conditional gene targeting in the mouse, we
      found that SHP2 is required for maintaining spermatogonial stem cells (SSCs) and
      the production of germ cells required for male fertility. After deleting SHP2,
      spermatogenesis was halted at the initial step during which transit-amplifying
      undifferentiated spermatogonia are produced from SSCs. In the absence of SHP2,
      proliferation of SSCs and undifferentiated spermatogonia was inhibited, thus germ
      cells cannot be replenished and SSCs cannot undergo renewal. However, germ cells
      beyond the undifferentiated spermatogonia stage of development at the time of
      SHP2 knockout were able to complete their maturation to become sperm. In cultures
      of SSCs and their progeny, inhibition of SHP2 activity reduced growth factor
      mediated intracellular signaling that regulates SSC proliferation and cell fate.
      Inhibition of SHP2 also decreased the number of SSCs present in culture and
      caused SSCs to detach from supporting cells. Injection of mice with an SHP2
      inhibitor blocked the production of germ cells from SSCs. Together, our studies
      show that SHP2 is essential for SSCs to maintain fertility and indicates that the
      pathogenesis of infertility in humans with SHP2 mutations is due to compromised
      SSC functions that block spermatogenesis.

PMID- 24123363
TI  - Stereoselective synthesis of (3R)-3-alkyl-4,1-benzoxazepine-2,5-diones.
AB  - Novel 3-alkyl-4,1-benzoxazepine-2,5-diones were synthesized in good ee exploiting
      the chiral pool methodology, an economical way of asymmetric synthesis. Various
      anthranilic acids are coupled with different alpha-haloacids to afford N-acylated
      anthranilic acid intermediates which undergo cyclization to (3R)-3-alkyl-4,1
      benzoxazepines-2,5-diones.

PMID- 24123362
TI  - On the confounding effect of temperature on chemical shift-encoded fat
      quantification.
AB  - PURPOSE: To characterize the confounding effect of temperature on chemical shift
      encoded (CSE) fat quantification. METHODS: The proton resonance frequency of
      water, unlike triglycerides, depends on temperature. This leads to a temperature
      dependence of the spectral models of fat (relative to water) that are commonly
      used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat
      water signals at various temperatures and echo time combinations. Oil-water
      phantoms were constructed and scanned at temperatures between 0 and 40 degrees C
      using spectroscopy and CSE imaging at three echo time combinations. An explanted
      human liver, rejected for transplantation due to steatosis, was scanned using
      spectroscopy and CSE imaging. Fat-water reconstructions were performed using four
      different techniques: magnitude and complex fitting, with standard or temperature
      corrected signal modeling. RESULTS: In all experiments, magnitude fitting with
      standard signal modeling resulted in large fat quantification errors. Errors were
      largest for echo time combinations near TEinit ~ 1.3 ms, DeltaTE ~ 2.2 ms. Errors
      in fat quantification caused by temperature-related frequency shifts were smaller
      with complex fitting, and were avoided using a temperature-corrected signal
      model. CONCLUSION: Temperature is a confounding factor for fat quantification. If
      not accounted for, it can result in large errors in fat quantifications in
      phantom and ex vivo acquisitions.

PMID- 24123364
TI  - Polymeric adducts of rhodium(II) tetraacetate with aliphatic diamines: natural
      abundance 13C and 15N CPMAS NMR investigations.
AB  - Complexation properties of dimeric rhodium(II) tetracarboxylates have been
      utilised in chemistry, spectroscopy and organic synthesis. Particularly, the
      combination of these rhodium salts with multifunctional ligands results in the
      formation of coordination polymers, and these are of interest because of their
      gas-occlusion properties. In the present work, the polymeric adducts of
      rhodium(II) tetraacetate with flexible ligands exhibiting conformational variety,
      ethane-1,2-diamine, propane-1,3-diamine and their N,N'-dimethyl- and N,N,N',N'
      tetramethyl derivatives, have been investigated by means of elemental analysis,
      (13)C CPMAS NMR, (15)N CPMAS NMR and density functional theory modelling.
      Elemental analysis and NMR spectra indicated the axial coordination mode and
      regular structures of (1 : 1)n oligomeric chains in the case of adducts of ethane
      1,2-diamine, N,N'-dimethylethane-1,2-diamine N,N,N',N'-tetramethylethane-1,2
      diamine and N,N,N',N'-tetramethylpropane-1,3-diamine. Propane-1,3-diamine and
      N,N'-dimethylpropane-1,3-diamine tended to form heterogeneous materials, composed
      of oligomeric (1 : 1)n chains and the additive of dirhodium units containing
      equatorially bonded ligands. Experimental findings have been supported by density
      functional theory modelling of some hypothetical structures and gauge-invariant
      atomic orbital calculations of NMR chemical shifts.

PMID- 24123365
TI  - Bhlhb5 is required for the subtype development of retinal amacrine and bipolar
      cells in mice.
AB  - BACKGROUND: BHLHB5, an OLIG-related basic helix-loop-helix transcription factor,
      is required for the development of a subset of gamma-amino butyric acid-releasing
      (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In
      order to determine BHLHB5's functional mechanism in retinogenesis, we used the
      Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells
      in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to
      activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing
      cells, and the cell fates of Bhlhb5-lineage cells were identified by using
      specific cell markers and were compared between normal and Bhlhb5-null retinas.
      RESULTS: In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells
      give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod
      photoreceptor cells during normal retinal development. Targeted deletion of
      Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine,
      dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of
      BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate
      into cholinergic amacrine cells. CONCLUSIONS: Our data reveal a broad expression
      pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as
      well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and
      bipolar subtypes.

PMID- 24123367
TI  - Controlled inkjetting of a conductive pattern of silver nanoparticles based on
      the coffee-ring effect.
AB  - Conductive patterns with line widths of 5-10 um are successfully fabricated by
      utilizing the coffee-ring effect in inkjet printing, resulting in transmittance
      values of up to 91.2% in the visible to near-infrared region. This non
      lithographic approach broadens the range of fabrication procedures that can be
      used to create various nanoparticle-based microstructures and electronic devices.

PMID- 24123366
TI  - Exome sequencing identifies potential risk variants for Mendelian disorders at
      high prevalence in Qatar.
AB  - Exome sequencing of families of related individuals has been highly successful in
      identifying genetic polymorphisms responsible for Mendelian disorders. Here, we
      demonstrate the value of the reverse approach, where we use exome sequencing of a
      sample of unrelated individuals to analyze allele frequencies of known causal
      mutations for Mendelian diseases. We sequenced the exomes of 100 individuals
      representing the three major genetic subgroups of the Qatari population (Q1
      Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33
      genes with effects on 36 clinically significant Mendelian diseases. These include
      variants not present in 1000 Genomes and variants at high frequency when compared
      with 1000 Genomes populations. Several of these Mendelian variants were only
      segregating in one Qatari subpopulation, where the observed subpopulation
      specificity trends were confirmed in an independent population of 386 Qataris.
      Premarital genetic screening in Qatar tests for only four out of the 37, such
      that this study provides a set of Mendelian disease variants with potential
      impact on the epidemiological profile of the population that could be
      incorporated into the testing program if further experimental and clinical
      characterization confirms high penetrance. 

PMID- 24123368
TI  - Is there a relationship between posttraumatic stress and growth after a lymphoma
      diagnosis?
AB  - OBJECTIVE: There are conflicting empirical data regarding the relationship
      between posttraumatic stress (PTS) and growth (PTG) observed in cancer survivors.
      Clarification of this association could inform evidence-based therapeutic
      recommendations to promote adjustment in survivors following a cancer diagnosis.
      METHODS: This cross-sectional study employed standardized measures to examine the
      association between PTS and PTG in a sample of long-term lymphoma survivors. In
      addition, associations between PTG and demographic, clinical and psychosocial
      variables were identified to inform clinical recommendations. RESULTS: Long-term
      survivors of non-Hodgkin lymphoma provided informed consent (n = 886; 74%
      response rate). Subjects averaged 10.2 years post-diagnosis and 62.9 years of
      age. No significant association was found between the PTS and PTG summary scores.
      Several demographic and clinical variables (e.g., female gender and greater
      social support) were independently associated with greater PTG. CONCLUSIONS:
      Clinicians are advised to be attentive to psychosocial needs throughout the post
      cancer diagnosis adjustment period by screening for PTS symptomatology and
      recognizing that survivors who report growth may also be highly distressed.

PMID- 24123369
TI  - CMR reference values for left ventricular volumes, mass, and ejection fraction
      using computer-aided analysis: the Framingham Heart Study.
AB  - PURPOSE: To determine sex-specific reference values for left ventricular (LV)
      volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided
      analysis and to examine the effect of age on LV parameters. MATERIALS AND
      METHODS: We examined data from 1494 members of the Framingham Heart Study
      Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a
      healthy reference group (without cardiovascular disease, hypertension, or LV wall
      motion abnormality) and determined sex-specific upper 95th percentile thresholds
      for LV volumes and mass, and lower 5th percentile thresholds for EF using
      computer-assisted border detection. In secondary analyses, we stratified
      participants by age-decade and tested for linear trend across age groups.
      RESULTS: The reference group comprised 685 adults (423F; 61 +/- 9 years). Men had
      greater LV volumes and mass, before and after indexation to common measures of
      body size (all P = 0.001). Women had greater EF (73 +/- 6 versus 71 +/- 6%; P =
      0.0002). LV volumes decreased with greater age in both sexes, even after
      indexation. Indexed LV mass did not vary with age. LV EF and concentricity
      increased with greater age in both sexes. CONCLUSION: We present CMR-derived LV
      reference values. There are significant age and sex differences in LV volumes,
      EF, and geometry, whereas mass differs between sexes but not age groups.

PMID- 24123370
TI  - MR lymphangiography with intradermal gadofosveset and human serum albumin in mice
      and primates.
AB  - PURPOSE: To investigate MR lymphangiography in mice and primates with intradermal
      Gadofosveset and human serum albumin. Gadofosveset is a US FDA approved small
      molecule Gadolinium (Gd) chelate (957 Da) which reversibly binds serum albumin
      and temporally behaves as a macromolecule. As the structure of albumin varies
      among species, the affinity of Gadofosveset is optimized for human albumin. In
      this study, Gadofosveset premixed with 10% human serum albumin (HSA) was injected
      intradermally in mice and monkeys, and then MR lymphangiography was performed on
      a 3.0 Tesla clinical scanner. MATERIALS AND METHODS: Twenty microliters of each
      agent was injected intradermally at both sides of the front and back paws using a
      30-gauge needle into female athymic nude mice (6-8 weeks old, n = 3 mice in each
      group). The performance of Gadofosveset-HSA was compared with Gd-labeled
      dendrimers (G4: 6 nm, G6: 10 nm) or Gd-DTPA. The target-to-muscle ratio (TMR =
      target signal intensity (SI)/muscle SI) was calculated at each time point. The
      TMRs were compared with a one-way analysis of variance followed by a Bonferroni
      multiple comparison test. RESULTS: Images taken as early as 2.5 min after
      intradermal (id) injection depicted enhanced lymph nodes using Gadofosveset-HSA
      (2.41 +/- 0.20). Up to 7.5 min after injection, TMRs of Gadofosveset-HSA were
      greater than those of dendrimers (G4 or G6-Gd-DTPA: 2.24 +/- 0.10, 2.12 +/- 0.11,
      respectively). By 15 min postinjection, TMRs of Gadofosveset-HSA (2.18 +/- 0.19)
      were comparable to Gd-labeled dendrimers (G4-Gd-DTPA: 2.37 +/- 0.15, G6-Gd-DTPA:
      2.25 +/- 0.18). Gadofosveset-HSA and Gd labeled dendrimers resulted in
      satisfactory MR lymphography in mice and monkeys. CONCLUSION: Because both
      Gadofosveset and HSA are approved for human use and Gadofosveset clears rapidly
      through the kidneys, this method has advantages over Gd-dendrimers and could be
      used for visualizing lymphatic drainage and detecting lymph nodes.

PMID- 24123371
TI  - Cysteine promoted C-terminal hydrazinolysis of native peptides and proteins.
AB  - Tagging the terminus: N->S acyl transfer in native peptides and proteins can be
      reliably intercepted with hydrazine. The method allows selective labeling and
      ligation, without recourse to the use of protein-splicing elements. NCL=native
      chemical ligation. 

PMID- 24123372
TI  - Simultaneous multi-slice excitation in spatially encoded NMR experiments.
AB  - Improved sensitivity: A novel strategy to enhance the experimental sensitivity in
      spatially encoded NMR experiments has been developed. The use of a multiple
      frequency modulated pulse applied simultaneously to an encoding gradient can
      afford a substantial sensitivity gain with respect to single-slice selected
      experiments. 

PMID- 24123373
TI  - Chronic cerebrolysin administration attenuates neuronal abnormalities in the
      basolateral amygdala induced by neonatal ventral hippocampus lesion in the rat.
AB  - The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of
      schizophrenia-related behavior in the rat. Our previous report demonstrated that
      cerebrolysin (Cbl), a neuropeptide preparation which mimics the action of
      endogenous neurotrophic factors on brain protection and repair, promoted recovery
      of dendritic and neuronal damage of the prefrontal cortex and nucleus accumbens
      and behavioral improvements in postpubertal nVHL rats. We recently demonstrated
      that nVHL animals exhibit dendritic atrophy and spine loss in the basolateral
      amygdala (BLA). This study aimed to determine whether Cbl treatment was capable
      of reducing BLA neuronal alterations observed in nVHL rats. The morphological
      evaluation included examination of dendrites using the Golgi-Cox procedure and
      stereology to quantify the total cell number in BLA. Golgi-Cox staining revealed
      that nVHL induced dendritic retraction and spine loss in BLA pyramidal neurons.
      Stereological analysis demonstrated nVHL also produced a reduction in cells in
      BLA. Interestingly, repeated Cbl treatment ameliorated dendritic pathology and
      neuronal loss in the BLA of the nVHL rats. Our data show that Cbl may foster
      recovery of BLA damage in postpubertal nVHL rats and suggests that the use of
      neurotrophic agents for the management of some schizophrenia-related symptoms may
      present an alternative therapeutic pathway in these disorders.

PMID- 24123374
TI  - Hematite-based water splitting with low turn-on voltages.

PMID- 24123375
TI  - Hepcidin plays a negative role in liver regeneration.
AB  - Hepcidin is a key regulator of iron metabolism. The expression of hepcidin is
      significantly induced by iron overload, inflammation, and infection of pathogens.
      Recent studies have indicated that the expression of hepcidin in the liver is
      also regulated during liver regeneration. However, the mechanism of the
      regulation of hepcidin expression and its role in liver regeneration remain
      unclear. In this study, we found that the hepatocyte growth factor inhibited
      hepcidin expression in the liver during the late stage of liver regeneration.
      Meanwhile, we investigated the effect of hepcidin on liver regeneration. Mice
      overexpressing hepcidin-1 exhibited impaired hepatic regeneration after partial
      hepatectomy, as determined by immunohistochemical staining of the proliferation
      cell nuclear antigen. Our results demonstrated a negative role of hepcidin in
      modulating liver regeneration, and suggested that a sustained high iron level by
      the down-regulation of hepcidin at the late stage of liver regeneration is
      required for hepatocyte proliferation. 

PMID- 24123376
TI  - The N-terminal nonapeptide of cephaibols A and C: a naturally occurring example
      of mismatched helical screw-sense control.
AB  - The N-terminal nonapeptide domain of the fungal nonribosomal peptide antibiotics
      cephaibol A and cephaibol C (AcPheAib4LeuIvaGly- Aib) is reported to adopt a
      right-handed helical conformation in the crystalline state. However, this
      conformation is at odds with the left-handed helicity observed in solution in
      related synthetic oligomers capped with Ac-L-PheAib4 fragments. We report the
      synthesis of four diastereoisomers of the cephaibol N-terminal nonapeptide, and
      show by NMR and CD spectroscopy that the peptide containing the chiral amino
      acids Phe and Leu in the naturally occurring relative configuration exists in
      solution as an interconverting mixture of helical screw-sense conformers. In
      contrast, the nonapeptide containing the unnatural relative configuration at Phe
      and Leu adopts a single, stable helical screw-sense, which is left handed when
      the N-terminal Phe residue is L and right-handed when the N-terminal Phe residue
      is D.

PMID- 24123377
TI  - Reduced functional connectivity within the limbic cortico-striato-thalamo
      cortical loop in unmedicated adults with obsessive-compulsive disorder.
AB  - Cortico-striato-thalamo-cortical (CSTC) loops project from the cortex to the
      striatum, then from the striatum to the thalamus via the globus pallidus, and
      finally from the thalamus back to the cortex again. These loops have been
      implicated in Obsessive-Compulsive Disorder (OCD) with particular focus on the
      limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate
      cortices, as well as the ventral striatum. Resting state functional-connectivity
      MRI (rs-fcMRI) studies, which examine temporal correlations in neural activity
      across brain regions at rest, have examined CSTC loop connectivity in patients
      with OCD and suggest hyperconnectivity within these loops in medicated adults
      with OCD. We used rs-fcMRI to examine functional connectivity within CSTC loops
      in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20).
      Contrary to prior rs-fcMRI studies in OCD patients on medications that report
      hyperconnectivity in the limbic CSTC loop, we found that compared with HCs,
      unmedicated OCD participants had reduced connectivity within the limbic CSTC
      loop. Exploratory analyses revealed that reduced connectivity within the limbic
      CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of
      limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential
      confounding effects of antidepressants on connectivity measures and the value of
      future examinations of the effects of pharmacological and/or behavioral
      treatments on limbic CSTC loop connectivity.

PMID- 24123378
TI  - EZH2 and KDM6A act as an epigenetic switch to regulate mesenchymal stem cell
      lineage specification.
AB  - The methyltransferase, Enhancer of Zeste homology 2 (EZH2), trimethylates histone
      3 lysine 27 (H3K27me3) on chromatin and this repressive mark is removed by lysine
      demethylase 6A (KDM6A). Loss of these epigenetic modifiers results in
      developmental defects. We demonstrate that Ezh2 and Kdm6a transcript levels
      change during differentiation of multipotential human bone marrow-derived
      mesenchymal stem cells (MSC). Enforced expression of Ezh2 in MSC promoted
      adipogenic in vitro and inhibited osteogenic differentiation potential in vitro
      and in vivo, whereas Kdm6a inhibited adipogenesis in vitro and promoted
      osteogenic differentiation in vitro and in vivo. Inhibition of EZH2 activity and
      knockdown of Ezh2 gene expression in human MSC resulted in decreased adipogenesis
      and increased osteogenesis. Conversely, knockdown of Kdm6a gene expression in MSC
      leads to increased adipogenesis and decreased osteogenesis. Both Ezh2 and Kdm6a
      were shown to affect expression of master regulatory genes involved in
      adipogenesis and osteogenesis and H3K27me3 on the promoters of master regulatory
      genes. These findings demonstrate an important epigenetic switch centered on
      H3K27me3 which dictates MSC lineage determination.

PMID- 24123379
TI  - Sclerotic lesions of the spine: MRI assessment.
AB  - Sclerotic (T2 dark) lesions of the spine are infrequent and, as a result, these
      are often missed or misdiagnosed. Plain films may not be always available during
      magnetic resonance imaging (MRI) readout. Knowledge of such lesions and their
      imaging appearances on MRI evaluation is essential for a reader. Additionally, a
      systematic approach is important to accurately diagnose these lesions. In this
      article we discuss the various causes of spinal sclerotic lesions, describe their
      MRI characteristics with relevant case examples, and outline a systematic
      approach to their evaluation.

PMID- 24123380
TI  - Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic
      tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic
      testing.
AB  - Cytogenetic aberrations identified by metaphase cytogenetics (MC) have
      diagnostic, prognostic, and therapeutic implications in myelodysplastic syndromes
      (MDS). However, in some MDS patients MC study is unsuccesful. Single nucleotide
      polymorphism array (SNP-A) based karyotyping could be helpful in these cases. We
      performed SNP-A in 62 samples from bone marrow or peripheral blood of primary MDS
      with an unsuccessful MC study. SNP-A analysis enabled the detection of
      aberrations in 31 (50%) patients. We used the copy number alteration information
      to apply the International Prognostic Scoring System (IPSS) and we observed
      differences in survival between the low/intermediate-1 and intermediate-2/high
      risk patients. We also saw differences in survival between very
      low/low/intermediate and the high/very high patients when we applied the revised
      IPSS (IPSS-R). In conclusion, SNP-A can be used successfully in PB samples and
      the identification of CNA by SNP-A improve the diagnostic and prognostic
      evaluation of this group of MDS patients.

PMID- 24123381
TI  - Synthesis of alkylbismuths by regiodivergent carbobismuthination of simple
      alkenes.
AB  - Switchable regioselectivity: This study represents the first carbobismuthination
      of alkenes achieved by the treatment of an alkene with a bismuth halide and a
      ketene silyl acetal. This reaction is particularly noteworthy in that a change in
      the type of halogen on a bismuth atom very easily switched the regioselectivity. 

PMID- 24123382
TI  - Analysis of oxcarbazepine and the 10-hydroxycarbazepine enantiomers in plasma by
      LC-MS/MS: application in a pharmacokinetic study.
AB  - Oxcarbazepine is a second-generation antiepileptic drug indicated as monotherapy
      or adjunctive therapy in the treatment of partial seizures or generalized tonic
      clonic seizures in adults and children. It undergoes rapid presystemic reduction
      with formation of the active metabolite 10-hydroxycarbazepine (MHD), which has a
      chiral center at position 10, with the enantiomers (S)-(+)- and R-(-)-MHD showing
      similar antiepileptic effects. This study presents the development and validation
      of a method of sequential analysis of oxcarbazepine and MHD enantiomers in plasma
      using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Aliquots of
      100 MUL of plasma were extracted with a mixture of methyl tert-butyl ether:
      dichloromethane (2:1). The separation of oxcarbazepine and the MHD enantiomers
      was obtained on a chiral phase Chiralcel OD-H column, using a mixture of
      hexane:ethanol:isopropanol (80:15:5, v/v/v) as mobile phase at a flow rate of 1.3
      mL/min with a split ratio of 1:5, and quantification was performed by LC-MS/MS.
      The limit of quantification was 12.5 ng oxcarbazepine and 31.25 ng of each MHD
      enantiomer/mL of plasma. The method was applied in the study of kinetic
      disposition of oxcarbazepine and the MHD enantiomers in the steady state after
      oral administration of 300 mg/12 h oxcarbazepine in a healthy volunteer. The
      maximum plasma concentration of oxcarbazepine was 1.2 ug/mL at 0.75 h. The
      kinetic disposition of MHD is enantioselective, with a higher proportion of the S
      (+)-MHD enantiomer compared to R-(-)-MHD and an AUC(0-12) S-(+)/R-(-) ratio of
      5.44.

PMID- 24123383
TI  - Movement disorder society unified Parkinson disease rating scale experiences in
      daily living: longitudinal changes and correlation with other assessments.
AB  - The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the
      goals of improving instructions and definitions, more accurately evaluating
      milder features, and assessing patient-reported outcomes and nonmotor features.
      To date, no study has evaluated longitudinal changes in components of the MDS
      UPDRS over time or correlated these with changes in other scales of various
      symptoms. We assessed Parts I and II of the MDS-UPDRS (non-Motor and Motor
      Experiences of Daily Living [nM-EDL, M-EDL]) as well as a number of other scales
      of motor, cognitive and behavioral function in a large population of patients (n
      = 383) with early- to mid-stage Parkinson's disease (PD) who had previously
      participated in a trial of a putative disease-modifying agent. Both parts of a
      MDS-UPDRS showed significant change over the 3-year follow-up period, with M-EDL
      scores declining to a greater extent than nM-EDL. Both the scores and their
      changes over time correlated relatively well with other rating scales of similar
      disease aspects. Modest correlations with the original version of the UPDRS
      supported the increased attention to nonmotor symptoms as well as milder levels
      of severity in the MDS-UPDRS. The M-EDL was much more sensitive to change over
      time in these early- to mid-stage patients than the original UPDRS Activities of
      Daily Living (ADL) scale. Finally, we showed no change over time in a small group
      of individuals with dopamine transporter single-photon emission computed
      tomography scans without evidence for dopamine deficiency. The nM-EDL and M-EDL
      components of the MDS-UPDRS provide an effective, relevant measure of change in
      the broad spectrum of symptoms of PD over the first decade of the disease.

PMID- 24123384
TI  - A toolbox of HSQC experiments for small molecules at high 13C-enrichment.
      Artifact-free, fully 13C-homodecoupled and JCC-encoding pulse sequences.
AB  - A set of modified HSQC experiments designed for the study of (13)C-enriched small
      molecules is introduced. It includes an improved sensitivity-enhanced HSQC
      experiment eliminating signal artifacts because of high-order (13)C magnetization
      terms generated at high (13)C enrichment. A broadband homonuclear (13)C
      decoupling sequence based on Zangger and Sterk's method simplifies the complex
      (13)C-(13)C multiplet structure in the F1 dimension of HSQC. When recording
      spectra at high resolution, the combination with a multiple-site modulation of
      the selective pulse outperforms the constant-time HSQC in terms of sensitivity
      and reliability. Finally, two pulse sequences reintroducing selected J(CC)
      couplings with selective pulses facilitate their assignments and measurements
      either in the splitting of the resulting doublets or by modulation of the signal
      amplitude. A sample of uniformly 92% (13)C-enriched cholesterol is used as an
      example.

PMID- 24123385
TI  - Metal-containing block copolymer thin films yield wire grid polarizers with high
      aspect ratio.
AB  - Highly selective etch masks are formed by thin films of a polystyrene-b
      poly(ferrocenylisopropylmethylsilane) diblock copolymer, PS-PFiPMS, containing
      hemicylindrical domains of PFiPMS. These domains, with a period of 35 nm, are
      readily aligned through mechanical shear. Aligned PS-PFiPMS templates are
      employed to fabricate high-aspect-ratio nanowire grids from amorphous silicon,
      which can polarize deep ultraviolet radiation, including 193 nm, at >90%
      efficiency. 

PMID- 24123386
TI  - Porous polymers by controlling phase separation during vapor deposition
      polymerization.
AB  - A template-free method is described to fabricate continuous-phase, porous polymer
      films by simultaneous phase separation during vapor deposition polymerization.
      The technique involves concurrent polymerization, crosslinking, and phase
      separation of condensed species and reaction products. Deposited films form open
      cell, macroporous structures consisting of crosslinked and glassy poly(glycidyl
      methacrylate). By limiting phase separation during vapor phase deposition,
      spatially dependent morphologies, such as layered morphologies, can be grown.
      Results show that combining vapor deposition polymerization with phase separation
      establishes morphological control, which may be applied to applications including
      cellular scaffolds, thin cushions and vibration dampers, and membranes for
      separations. 

PMID- 24123387
TI  - Selective reductive cleavage of inert aryl C-O bonds by an iron catalyst.

PMID- 24123388
TI  - Lung injury induced by secondhand smoke exposure detected with hyperpolarized
      helium-3 diffusion MR.
AB  - PURPOSE: To determine whether helium-3 diffusion MR can detect the changes in the
      lungs of healthy nonsmoking individuals who were regularly exposed to secondhand
      smoke. MATERIALS AND METHODS: Three groups were studied (age: 59 +/- 9 years): 23
      smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We
      measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s.
      RESULTS: One-way analysis of variance revealed that the mean area under the
      helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated
      compared with the controls and to the exposure-to-secondhand-smoke subjects (P <
      0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand
      smoke subjects and that of the controls was found (P = 0.115). However,
      application of a receiver operator characteristic-derived rule to classify
      subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30%
      (11/37) of the exposure-to-secondhand subjects were classified as "smokers"
      indicating an elevation of the ADC AUC. CONCLUSION: Using helium-3 diffusion MR,
      elevated ADC values were detected in 30% of nonsmoking healthy subjects who had
      been regularly exposed to secondhand smoke, supporting the concept that, in
      susceptible individuals, secondhand smoke causes mild lung damage.

PMID- 24123390
TI  - Changes in psychological adjustment over the course of treatment for breast
      cancer: the predictive role of social sharing and social support.
AB  - BACKGROUND: Although research on social sharing suggests it could be an important
      factor in subsequent adjustment, it has rarely been examined in combination with
      the nature of the support received by patients. The goal of this study was to
      determine whether and to what extent social sharing concerning the disease and
      perceived social support after breast surgery explain psychological adjustment at
      the end of the treatment. METHODS: One hundred two participants were recruited
      consecutively at a large cancer care center (Gustave Roussy, France). After
      surgery (T1) and at the end of the adjuvant treatment (T2), patients responded to
      self-report questionnaires assessing psychological adjustment (depressive
      symptoms and cancer-related distress), social sharing concerning the illness, and
      perceived social support (generic and cancer specific). RESULTS: When the initial
      levels of adjustment were controlled for, hierarchical multiple regression models
      showed that greater instrumental support at T1 accounted for favorable changes in
      depressive symptoms at T2. In contrast, the perception of aversive attitudes in
      the environment and the avoidance of social sharing explained an increase in
      intrusive cancer-related thoughts. CONCLUSION: The results suggest a negative
      impact of aversive attitudes from the environment on adjustment during treatment.
      It also confirms the importance of practical aspects of social support after
      surgery. In line with Lepore theory, sharing about the illness in a supportive
      environment may be of primary importance in the cognitive processing of cancer
      and thus may promote adjustment. These results have original implications for the
      counseling of patients and their relatives.

PMID- 24123391
TI  - Amnestic multiple cognitive domains impairment and periventricular white matter
      hyperintensities are independently predictive factors progression to dementia in
      mild cognitive impairment.
AB  - OBJECTIVE: Mild cognitive impairment (MCI) usually represents a transitional
      phase between normal cognitive function and dementia, but not all people with MCI
      develop dementia because MCI is a clinically and etiologically heterogeneous
      grouping. The aim of this study was to determine whether clinical subtypes of MCI
      and severity of white matter hyperintensities (WMH) were associated with
      progression of MCI to dementia. METHOD: Our study cohort consisted of 840
      patients aged 55 years or older who had a diagnosis of MCI at their baseline
      visit and had at least one follow-up contact after baseline. RESULTS: The results
      of the multivariable Cox proportional hazards model analysis revealed that both
      multiple domain amnestic MCI with WMH and multiple domain amnestic MCI without
      WMH were a significantly more likely to progress to dementia in comparison with
      patients with non-amnestic MCI. Logistic regression analyses showed that PWMH
      (periventricular white matter hyperintensities), not the deep white matter
      hyperintensities, was significantly associated with incident dementia.
      CONCLUSIONS: This study showed that mdMCI + a (-NL or -WMH) are more associated
      with progression to dementia. We also found that increasing severity of PWMH, not
      deep white matter hyperintensities, was significantly associated with incident
      dementia, independently of subtype of MCI. It suggests that both mdMCI + a and
      PWMH are good prognostic factors of progression to dementia in MCI.

PMID- 24123389
TI  - Noninvasive imaging of infection after treatment with tumor-homing bacteria using
      Chemical Exchange Saturation Transfer (CEST) MRI.
AB  - PURPOSE: To develop a noninvasive MRI method for determining the germination and
      infection of tumor-homing bacteria in bacteriolytic cancer therapy using
      endogenous CEST contrast. METHODS: The CEST parameters of the anaerobic gram
      positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in
      vitro, then used to detect C. novyi-NT germination and infection in subcutaneous
      CT26 colorectal tumor-bearing mice (n = 6) after injection of 300 million
      bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that
      the changes of CEST MRI were due to inflammation. RESULTS: CEST contrast was
      observed over a broad frequency range for bacterial suspensions in vitro, with
      the maximum contrast around 2.6 ppm from the water resonance. No signal could be
      detected for bacterial spores, demonstrating the specificity for germination. In
      vivo, a significant elevation of CEST contrast was identified in C. novyi-NT
      infected tumors as compared to those before bacterial germination and infection
      (P < 0.05; n = 6). No significant change was observed in tumors with LPS-induced
      sterile inflammation (P > 0.05; n = 4). CONCLUSION: Endogenous bacterial CEST
      contrast (bacCEST) can be used to monitor the germination and proliferation of
      the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling
      probes.

PMID- 24123392
TI  - Analysis of three MU1-AP1 subunits during zebrafish development.
AB  - BACKGROUND: The family of AP-1 complexes mediates protein sorting in the late
      secretory pathway and it is essential for the development of mammals. The
      ubiquitously expressed AP-1A complex consists of four adaptins gamma1, beta1,
      MU1A, and sigma1A. AP-1A mediates protein transport between the trans-Golgi
      network and early endosomes. The polarized epithelia AP-1B complex contains the
      MU1B-adaptin. AP-1B mediates specific transport of proteins from basolateral
      recycling endosomes to the basolateral plasma membrane of polarized epithelial
      cells. RESULTS: Analysis of the zebrafish genome revealed the existence of three
      MU1-adaptin genes, encoding MU1A, MU1B, and the novel isoform MU1C, which is not
      found in mammals. MU1C shows 80% sequence identity with MU1A and MU1B. The MU1C
      expression pattern largely overlaps with that of MU1A, while MU1B is expressed in
      epithelial cells. By knocking-down the synthesis of MU1A, MU1B and MU1C with
      antisense morpholino techniques we demonstrate that each of these MU1 adaptins is
      essential for zebrafish development, with MU1A and MU1C being involved in central
      nervous system development and MU1B in kidney, gut and liver formation.
      CONCLUSIONS: Zebrafish is unique in expressing three AP-1 complexes: AP-1A, AP
      1B, and AP-1C. Our results demonstrate that they are not redundant and that each
      of them has specific functions, which cannot be fulfilled by one of the other
      isoforms. Each of the MU1 adaptins appears to mediate specific molecular
      mechanisms essential for early developmental processes, which depends on specific
      intracellular vesicular protein sorting pathways.

PMID- 24123393
TI  - Pd-catalyzed coupling of non-activated dibromoarenes to 2,3-diaminoarenes:
      formation of N,N'-dihydropyrazines.

PMID- 24123394
TI  - Extreme growth failure is a common presentation of ligase IV deficiency.
AB  - Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage
      syndrome owing to a shared predisposition to lympho-reticular malignancies,
      significant microcephaly, and radiation hypersensitivity. Only 16 cases with
      mutations in LIG4 have been described to date with phenotypes varying from
      malignancy in developmentally normal individuals, to severe combined
      immunodeficiency and early mortality. Here, we report the identification of
      biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial
      dwarfism presenting with restricted prenatal growth and extreme postnatal global
      growth failure (average OFC -10.1 s.d., height -5.1 s.d.). Subsequently, most
      patients developed thrombocytopenia and leucopenia later in childhood and many
      were found to have previously unrecognized immunodeficiency following molecular
      diagnosis. None have yet developed malignancy, though all patients tested had
      cellular radiosensitivity. A genotype-phenotype correlation was also noted with
      position of truncating mutations corresponding to disease severity. This work
      extends the phenotypic spectrum associated with LIG4 mutations, establishing that
      extreme growth retardation with microcephaly is a common presentation of
      bilallelic truncating mutations. Such growth failure is therefore sufficient to
      consider a diagnosis of LIG4 deficiency and early recognition of such cases is
      important as bone marrow failure, immunodeficiency, and sometimes malignancy are
      long term sequelae of this disorder. 

PMID- 24123396
TI  - Three-dimensional assessment of lung tissue density using a clinical ultrashort
      echo time at 3 tesla: a feasibility study in healthy subjects.
AB  - PURPOSE: To implement and assess the performance of three-dimensional (3D) ultra
      short echo (UTE) time for evaluating lung tissue density changes induced by
      gravity dependence and lung inflation. MATERIALS AND METHODS: Twelve healthy
      volunteers were imaged by 3D UTE at 3 Tesla, during free-breathing and
      breathholding of the subjects. MR signal intensities were measured in lung tissue
      and muscle regions. The variations of MR lung signal intensity and lung water
      content were evaluated as a function of lung inflation and anterior/posterior
      position. RESULTS: SNR in lung tissue ranged between 35 for free-breathing
      acquisitions and 7 for breathhold acquisitions at functional residual capacity.
      Lung-to-muscle signal ratios decreased from 0.58 in posterior areas to 0.34 in
      anterior areas. The average water content measured in lungs was equal to 34% and
      58% in gravitationally nondependent and dependent regions of interest.
      CONCLUSION: The 3D UTE lung MRI provides signal within lung parenchyma and can be
      used to assess lung tissue density.

PMID- 24123395
TI  - DNA glycosylases search for and remove oxidized DNA bases.
AB  - This review article presents, an overview of the DNA glycosylases that recognize
      oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how
      structure can inform function. For example, even though human NEIL1 and the plant
      and fungal orthologs lack the zinc finger shown to be required for binding, DNA
      crystal structures revealed a "zincless finger" with the same properties.
      Moreover, the "lesion recognition loop" is not involved in lesion recognition,
      rather, it stabilizes 8-oxoG in the active site pocket. Unlike the other Fpg/Nei
      family members, Neil3 lacks two of the three void-filling residues that stabilize
      the DNA duplex and interact with the opposite strand to the damage which may
      account for its preference for lesions in single-stranded DNA. Also single
      molecule approaches show that DNA glycosylases search for their substrates in a
      sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix
      to probe for the presence of damage.

PMID- 24123397
TI  - Rhodium-catalyzed oxidative C-H activation/cyclization for the synthesis of
      phosphaisocoumarins and phosphorous 2-pyrones.
AB  - Rhodium-catalyzed cyclization of phosphinic acids and phosphonic monoesters with
      alkynes has been developed. The oxidative annulation proceeds with complete
      conversion of phosphinic acid derivatives and allowed the atom-economic
      preparation of useful phosphaisocoumarins with high yield and selectivity. The
      reaction is tolerant of extensive substitution on the phosphinic acid, phosphonic
      monoester and alkyne, including halides, ketone, and hydroxyl groups as
      substituents. Furthermore, we found that alkenylphosphonic monoesters proceed to
      give a wide range of phosphorus 2-pyrones through oxidative annulation with
      alkynes. Mechanistic studies revealed that C-H bond metalation was the rate
      limiting step.

PMID- 24123399
TI  - Catalytic asymmetric 1,3-dipolar cycloaddition of two different ylides: facile
      access to chiral 1,2,4-triazinane frameworks.
AB  - Ylides at a crossing: An unprecedented 1,3-dipolar cycloaddition (cross
      cycloaddition) between two different ylides was realized by using the chiral
      Cu(I) /tBu-Phosferrox complex as the catalyst under mild reaction conditions.
      This catalytic system provides an expeditious approach to the construction of
      highly functionalized 1,2,4-triazinane derivatives in good yields with excellent
      diastereoselectivities and enantioselectivities. 

PMID- 24123400
TI  - Liver dynamic contrast-enhanced MRI for staging liver fibrosis in a piglet model.
AB  - PURPOSE: To determine whether dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) could monitor progression of liver fibrosis in a piglet model,
      and which DCE-MRI parameter is most accurate for staging this disease. MATERIALS
      AND METHODS: Sixteen piglets were prospectively used to model liver fibrosis and
      underwent liver DCE-MRI followed by biopsy on the 0, 5th, 9th, 16th, and 21st
      weekends after modeling of fibrosis. Time of peak (TOP), time to peak (TTP),
      positive enhancement integral (PEI), maximum slope of increase (MSI), and maximum
      slope of decrease (MSD) were measured and statistically analyzed for the
      monitoring and staging. RESULTS: As fibrosis progresses, TOP and TTP tended to
      increase, whereas MSI, MSD, and PEI tended to decrease (all P < 0.05). TOP, TTP,
      and MSI could discriminate fibrosis stage 0 from 1-4, 0-1 from 2-4, 0-2 from 3-4,
      and 0-3 from 4; PEI could distinguish the above-mentioned stages except 0-3 from
      4; and MSD could distinguish stage 0-3 from 4, and 0 from 1-4 (all P < 0.05). For
      predicting stage >=1, >=2, and >=3, the area under receiver operating
      characteristic curve (AUC) of MSI was largest among all parameters; for stage 4
      AUC of TTP was largest. CONCLUSION: DCE-MRI has the potential to dynamically
      stage progression of liver fibrosis.

PMID- 24123398
TI  - Concise review: Sowing the seeds of a fruitful harvest: hematopoietic stem cell
      mobilization.
AB  - Hematopoietic stem cell transplantation is the only curative option for a number
      of malignant and nonmalignant diseases. As the use of hematopoietic transplant
      has expanded, so too has the source of stem and progenitor cells. The predominate
      source of stem and progenitors today, particularly in settings of autologous
      transplantation, is mobilized peripheral blood. This review will highlight the
      historical advances which led to the widespread use of peripheral blood stem
      cells for transplantation, with a look toward future enhancements to mobilization
      strategies.

PMID- 24123402
TI  - Growth, development and obesity in developing countries.

PMID- 24123403
TI  - Question 1: Prednisolone or dexamethasone for acute exacerbations of asthma: do
      they have similar efficacy in the management of exacerbations of childhood
      asthma?

PMID- 24123401
TI  - A two-factor theory for concussion assessment using ImPACT: memory and speed.
AB  - We present the initial validation of a two-factor structure of Immediate Post
      Concussion Assessment and Cognitive Testing (ImPACT) using ImPACT composite
      scores and document the reliability and validity of this factor structure. Factor
      analyses were conducted for baseline (N = 21,537) and post-concussion (N = 560)
      data, yielding "Memory" (Verbal and Visual) and "Speed" (Visual Motor Speed and
      Reaction Time) Factors; inclusion of Total Symptom Scores resulted in a third
      discrete factor. Speed and Memory z-scores were calculated, and test-retest
      reliability (using intra-class correlation coefficients) at 1 month (0.88/0.81),
      1 year (0.85/0.75), and 2 years (0.76/0.74) were higher than published data using
      Composite scores. Speed and Memory scores yielded 89% sensitivity and 70%
      specificity, which was higher than composites (80%/62%) and comparable with
      subscales (91%/69%). This emergent two-factor structure has improved test-retest
      reliability with no loss of sensitivity/specificity and may improve understanding
      and interpretability of ImPACT test results.

PMID- 24123405
TI  - Question 2: Do weighted blankets improve sleep in children with an autistic
      spectrum disorder?

PMID- 24123407
TI  - Single-chain self-folding of synthetic polymers induced by metal-ligand
      complexation.
AB  - The controlled folding of a single polymer chain is for the first time realized
      by metal- complexation. alpha,omega-Bromine functional linear polymers are
      prepared via activators regenerated by electron transfer (ARGET) ATRP (M-n,SEC =
      5900 g mol(-1) , D = 1.07 and 12 000 g mol(-1) , D = 1.06) and the end groups of
      the polymers are subsequently converted to azide functionalities. A copper
      catalyzed azide-alkyne cycloaddition (CuAAC) reaction is carried out in the
      presence of a novel triphenylphosphine ligand and the polymers to afford
      homotelechelic bis-triphenylphosphine polymeric-macroligands (MLs) (M-n,SEC =
      6600 g mol(-1) , D = 1.07, and 12 800 g mol(-1) , D = 1.06). Single-chain metal
      complexes (SCMCs) are formed in the presence of Pd(II) ions in highly diluted
      solution at ambient temperature. The results derived via (1) H and (31) P{(1) H}
      NMR experiments, SEC, and DLS unambiguously evidence the efficient formation of
      SCMCs via metal ligand complexation. 

PMID- 24123408
TI  - Marked heterogeneity of HER2/NEU gene amplification in endometrial serous
      carcinoma.
AB  - Significant heterogeneity of HER2 protein expression has been recently observed
      in HER2 positive endometrial serous carcinomas. Tumor cells with HER2
      overexpression and/or gene amplification in a heterogeneous tumor may represent a
      biologically more aggressive subclone that is clinically relevant to prognosis
      and potential targeted therapy. To correlate with HER2 protein heterogeneity, we
      investigated the heterogeneity of HER2/NEU gene amplification in endometrial
      serous carcinoma. A total of 17 endometrial serous carcinomas with heterogeneous
      HER2 protein expression were selected for the study, including nine cases with a
      3+ and eight cases with a 2+ immunohistochemical score. Initial reflex HER2 FISH
      was available for seven of the eight 2+ cases, five of which showed HER2/NEU gene
      amplification. All 17 cases underwent repeat FISH targeting larger tumor tissue
      areas. Ten cases (72%) displayed striking heterogeneity of HER2/NEU gene copy
      number in the form of cluster amplification. Diffuse HER2 amplification was
      observed in four cases, no amplification was seen in three tumors. In cases with
      cluster amplification, HER2 protein overexpression by immunohistochemistry
      closely correlated at the cellular level with HER2/NEU gene amplification. In
      conclusion, the significant percentage of cases with heterogeneous HER2/NEU gene
      amplification indicates that the existing HER2 testing guidelines designed for
      breast cancer may not be applicable to endometrial serous carcinoma. Clinical
      testing on multiple different tumor samples or large tumor tissue sections is
      recommended for both immunohistochemistry and FISH assessment of HER2 status.
      Direct comparison with the HER2 immunostaining pattern may be helpful in
      detecting HER2 amplified areas in a heterogeneous tumor.

PMID- 24123409
TI  - Imaging neurodegeneration in the mouse hippocampus after neonatal hypoxia
      ischemia using oscillating gradient diffusion MRI.
AB  - PURPOSE: To investigate if frequency-dependent contrasts using oscillating
      gradient diffusion MRI (dMRI) can detect hypoxia-ischemia (HI) -induced
      neurodegeneration in the neonatal mouse hippocampus. METHODS: Pulsed- and
      oscillating-gradient dMR images (at 50, 100, and 150 Hz) were acquired from
      postmortem fixed brains of mice exposed to neonatal HI using the Rice-Vanucci
      model. MRI data were acquired at 1, 4, and 8 days following HI, and compared with
      histological data from the same mice for in situ histological validation of the
      MRI findings. RESULTS: The rate of change of apparent diffusion coefficient with
      gradient frequency (Deltaf ADC) revealed unique layer-specific contrasts in the
      neonatal mouse hippocampus. Deltaf ADC measurements were found to show a
      significant decrease in response to neonatal HI injury, in the pyramidal (Py) and
      granule (GrDG) cell layers compared with contralateral regions. The areas of
      reduced intensity in the Deltaf ADC maps corresponded to regional
      neurodegeneration seen with H&E and Fluoro-Jade C stainings, indicating that
      alterations in Deltaf ADC contrasts are sensitive to early microstructural
      changes due to HI-induced neurodegeneration in the studied regions. CONCLUSION:
      The findings show that the frequency-dependence of ADC measurements with
      oscillating-gradient dMRI can provide a sensitive contrast to detect HI-induced
      neurodegeneration in neuronal layers of the neonatal mouse hippocampus.

PMID- 24123410
TI  - Enantiopurity determination of the enantiomers of the triple reuptake inhibitor
      indatraline.
AB  - The present study describes the development of two approaches for the
      determination of the enantiopurity of both enantiomers of indatraline. Initially,
      a method was developed using different chiral solvating agents (CSAs) for
      diastereomeric discrimination regarding signal separation in (1)H nuclear
      magnetic resonance (NMR) spectroscopy, revealing MTPA as a promising choice for
      the differentiation of the indatraline enantiomers. This CSA was also tested for
      its ideal molar ratio, temperature, and solvent. Optimized conditions could be
      achieved that made determination of enantiopurity for (1R,3S)-indatraline up to
      98.9% enantiomeric excess (ee) possible. To quantify even higher enantiopurities,
      a high-performance liquid chromatography (HPLC) method based on a modified beta
      cyclodextrine phase was established. The influence of buffer type, concentration,
      pH value, percentage and kind of organic modifier, temperature, injection volume
      as well as sample solvent on chromatographic parameters was investigated.
      Afterwards, the reliability of the established HPLC method was demonstrated by
      validation according to the ICH guideline Q2(R1) regarding specificity, accuracy,
      precision, linearity, and quantitation limit. The developed method proved to be
      strictly linear within a concentration range of 1.25-1000 MUM for the (1R,3S)
      enantiomer and 1.25-750 MUM for its mirror image that enables a reliable
      determination of enantiopurities up to 99.75% ee for the (1R,3S)-enantiomer and
      up to 99.67% ee for the (1S,3R)-enantiomer.

PMID- 24123411
TI  - Glimpse into Hox and tale regulation of cell differentiation and reprogramming.
AB  - During embryonic development, cells become gradually restricted in their
      developmental potential and start elaborating lineage-specific transcriptional
      networks to ultimately acquire a unique differentiated state. Hox genes play a
      central role in specifying regional identities, thereby providing the cell with
      critical information on positional value along its differentiation path. The
      exquisite DNA-binding specificity of the Hox proteins is frequently dependent
      upon their interaction with members of the TALE family of homeodomain proteins.
      In addition to their function as Hox-cofactors, TALE homeoproteins control
      multiple crucial developmental processes through Hox-independent mechanisms.
      Here, we will review recent findings on the function of both Hox and TALE
      proteins in cell differentiation, referring mostly to vertebrate species. In
      addition, we will discuss the direct implications of this knowledge on cell
      plasticity and cell reprogramming.

PMID- 24123413
TI  - A comparison of FDG-PET and blood flow SPECT in the diagnosis of
      neurodegenerative dementias: a systematic review.
AB  - OBJECTIVE: Perfusion single photon emission computed tomography (SPECT) and 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) both have clinical
      utility for the differential diagnosis of dementia. Although PET is often viewed
      by some as more accurate and therefore preferential, the extent to which
      published evidence supports this is not clear. The aim of this review was to
      address the question by reviewing studies of SPECT and PET imaging in dementia
      diagnosis, with a particular focus on all published head-to-head studies. DESIGN:
      A MEDLINE search was carried out using the following keywords: "PET" and "SPECT"
      and "dementia" or "Mild Cognitive Impairment," together with "alzheimers" or
      "DLB" or "lewy body" or "frontotemporal" or "FTD" or "Picks." Articles were
      included up to February 2013, limited to human studies and in English language.
      RESULTS: Published studies of SPECT accuracy show that it is a useful tool for
      differential diagnosis, with sensitivities of 65-85% for diagnosing Alzheimer's
      disease (AD) and specificities (for other neurodegenerative dementias) of 72-87%.
      PET studies generally report higher accuracy, with sensitivities of 75-99% for AD
      and specificities of 71-93%. However, there have been few direct head-to-head
      comparisons, with some indicating SPECT and PET to be equally useful in dementia
      diagnosis and others favouring PET. Many of these studies are limited with
      respect to numbers and methodically with poorly matched control groups.
      CONCLUSIONS: Overall, although studies suggest superiority of PET over SPECT, the
      evidence base for this is actually quite limited. We suggest that further direct
      comparative studies, including health economic and patient preference
      evaluations, are needed to help direct future service provision.

PMID- 24123414
TI  - Modular total synthesis of rhizopodin: a highly potent G-actin dimerizing
      macrolide.
AB  - A highly convergent total synthesis of the potent polyketide macrolide rhizopodin
      has been achieved in 29 steps by employing a concise strategy that exploits the
      molecule's C2 symmetry. Notable features of this convergent approach include a
      rapid assembly of the macrocycle through a site-directed sequential cross
      coupling strategy and the bidirectional attachment of the side chains by means of
      Horner-Wadsworth-Emmons (HWE) coupling reactions. During the course of this
      endeavor, scalable routes for synthesis of three main building blocks of similar
      complexity were developed that allowed for their stereocontrolled construction.
      This modular route will be amenable to the development of syntheses of other
      analogues of rhizopodin.

PMID- 24123412
TI  - Connectome-scale assessments of structural and functional connectivity in MCI.
AB  - Mild cognitive impairment (MCI) has received increasing attention not only
      because of its potential as a precursor for Alzheimer's disease but also as a
      predictor of conversion to other neurodegenerative diseases. Although MCI has
      been defined clinically, accurate and efficient diagnosis is still challenging.
      Although neuroimaging techniques hold promise, compared to commonly used
      biomarkers including amyloid plaques, tau protein levels and brain tissue
      atrophy, neuroimaging biomarkers are less well validated. In this article, we
      propose a connectomes-scale assessment of structural and functional connectivity
      in MCI via two independent multimodal DTI/fMRI datasets. We first used DTI
      derived structural profiles to explore and tailor the most common and consistent
      landmarks, then applied them in a whole-brain functional connectivity analysis.
      The next step fused the results from two independent datasets together and
      resulted in a set of functional connectomes with the most differentiation power,
      hence named as "connectome signatures." Our results indicate that these
      "connectome signatures" have significantly high MCI-vs-controls classification
      accuracy, at more than 95%. Interestingly, through functional meta-analysis, we
      found that the majority of "connectome signatures" are mainly derived from the
      interactions among different functional networks, for example, cognition
      perception and cognition-action domains, rather than from within a single
      network. Our work provides support for using functional "connectome signatures"
      as neuroimaging biomarkers of MCI.

PMID- 24123415
TI  - Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.
AB  - Extracellular purines elicit strong signals in the nervous system. Adenosine-5'
      triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous
      cells secrete ATP by exocytosis or through plasma membrane proteins such as
      connexin hemichannels. Using a combination of imaging, luminescence and
      electrophysiological techniques, we explored the possibility that Connexin 32
      (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous
      system could be an important source of ATP in peripheral nerves. We triggered the
      release of ATP in vivo from mice sciatic nerves by electrical stimulation and
      from cultured SCs by high extracellular potassium concentration-evoked
      depolarization. No ATP was detected in the extracellular media after treatment of
      the sciatic nerve with Octanol or Carbenoxolone, and ATP release was
      significantly inhibited after silencing Cx32 from SCs cultures. We investigated
      the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis
      oocytes. We found that ATP release is coupled to the inward tail current
      generated after the activation of Cx32 hemichannels by depolarization pulses, and
      it is sensitive to low extracellular calcium concentrations. Moreover, we found
      altered ATP release in mutated Cx32 hemichannels related to the X-linked form of
      Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in
      peripheral nerves could underlie the physiopathology of this neuropathy.

PMID- 24123416
TI  - The Basic Documentation for Psycho-Oncology (PO-Bado): an innovative tool to
      combine screening for psychological distress and patient support at cancer
      diagnosis.
AB  - OBJECTIVES: The Basic Documentation for Psycho-Oncology (PO-Bado) is a semi
      directive instrument for assessing psychosocial difficulties in cancer patients.
      It is based on subjective status and not on degree of symptom severity. Our
      objectives were to assess whether use of the PO-Bado during post-cancer-diagnosis
      consultations improves the quality of communication by establishing a supportive
      relationship between nurses and patients and to assess nurses' satisfaction of
      their communication skills. METHODS: Data were collected from post-diagnosis 'bad
      news' consultations across four Cancer treatment centres in South West France.
      Eleven nurses who had never used the PO-Bado ('inexperienced group') received
      training on the instrument (short-form). Twenty-one pre-training consultations
      without the PO-Bado were recorded and compared with 21 post-training
      consultations with the PO-Bado. Twenty consultations with four nurses with
      experience using the PO-Bado ('experienced group') were included for between
      group comparisons. Nurses' satisfaction was evaluated through semi-directive
      consultations at the end of the study and completed by a visual analogue scale.
      RESULTS: We transcribed and analysed 62 consultations. We observed greater use of
      techniques encouraging patient expression in consultations with PO-Bado
      experienced nurses (p < 0.01); after PO-Bado training for 'inexperienced' nurses
      (p < 0.05) and less use of non-encouraging techniques after PO-Bado training for
      'inexperienced' nurses (p < 0.01). Nurses felt more satisfied with their
      communications skills after PO-Bado training and stated that they felt more
      competent, particularly for referrals to psychologists. CONCLUSIONS: The PO-Bado
      is beneficial for the quality of the communication between nurses and patients at
      bad-news delivery consultations and for the satisfaction of nurses with regard to
      their relational skills.

PMID- 24123417
TI  - Four new prenylated flavonoids from the roots of Cudrania tricuspidata.
AB  - Four new prenylated flavonoids, cudraflavanones E-F (1-2) and cudraflavones F-G
      (6-7), together with eight known compounds were isolated from the roots of
      Cudrania tricuspidata. The structures of new compounds were elucidated on the
      basis of extensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS and
      CD.

PMID- 24123418
TI  - Iodine-iodine bonding makes tetra(diiodine)chloride, [Cl(I2)4]-, planar.

PMID- 24123419
TI  - Hierarchical porous graphene/polyaniline composite film with superior rate
      performance for flexible supercapacitors.
AB  - A highly flexible graphene free-standing film with hierarchical structure is
      prepared by a facile template method. With a porous structure, the film can be
      easily bent and cut, and forms a composite with another material as a scaffold.
      The 3D graphene film exhibits excellent rate capability and its capacitance is
      further improved by forming a composite with polyaniline nanowire arrays. The
      flexible hierarchical composite proves to be an excellent electrode material for
      flexible supercapacitors. 

PMID- 24123421
TI  - Why buy an expensive ($7 million) 7T MRI system for biomedical research?

PMID- 24123420
TI  - Clinical evaluation of CAIPIRINHA: comparison against a GRAPPA standard.
AB  - PURPOSE: To evaluate image quality when using a CAIPIRINHA sampling pattern in
      comparison to a standard GRAPPA sampling pattern in patients undergoing a routine
      three-dimensional (3D) breathheld liver exam. CAIPIRINHA uses an optimized phase
      encoding sampling strategy to alter aliasing artifacts in 3D acquisitions to
      improve parallel imaging reconstruction. MATERIALS AND METHODS: Twenty patient
      volunteers were scanned using a 3D VIBE acquisition with an acceleration factor
      of four using a CAIPIRINHA and standard GRAPPA sampling pattern. CAIPIRINHA and
      GRAPPA images were evaluated by three radiologists in a two alternative forced
      choice test, and the Wilcoxon signed rank test was performed. RESULTS: The
      CAIPIRINHA sampling pattern was preferred in an average of 68% of the
      comparisons, and the Wilcoxon signed rank test showed a significant improvement
      in CAIPIRINHA images (P = 0.014). This analysis indicates that in the given
      sample set, CAIPIRINHA preference over the GRAPPA standard was statistically
      significant. CONCLUSION: This work shows that for an acceleration factor of four,
      a CAIPIRINHA accelerated VIBE acquisition provides significantly improved image
      quality in comparison to the current GRAPPA standard. This allows a further
      reduction in imaging time for similar spatial resolutions, which can reduce long
      breathhold requirements in abdominal imaging, and may be particularly helpful in
      patients who cannot provide requisite breathholds with current protocols.

PMID- 24123422
TI  - Glycosylation of pramlintide: synthetic glycopeptides that display in vitro and
      in vivo activities as amylin receptor agonists.

PMID- 24123423
TI  - Rhodium-catalyzed denitrogenative [2,3] sigmatropic rearrangement: an efficient
      entry to sulfur-containing quaternary centers.

PMID- 24123424
TI  - Reliable metal deposition into TiO(2) nanotubes for leakage-free interdigitated
      electrode structures and use as a memristive electrode.
AB  - Nearly 100 % filling of TiO2 nanotubes with metals, including Ag, Cu, Au, and Pt,
      was achieved by defect-sealing treatment at the bottom of the nanotubes, followed
      by metal deposition using nuclei formation/coalescence. The resulting short
      circuit-free interdigitated electrode configurations can, for example, be used to
      fabricate memristive electrodes. 

PMID- 24123425
TI  - Enantioselective liquid-liquid extraction of zopiclone with mandelic acid ester
      derivatives.
AB  - Enantioselective liquid-liquid extraction of zopiclone was conducted by employing
      a series of (R)-mandelic acid esters as chiral extractants. The effects of
      concentration of extractant, concentration of zopiclone, type of organic solvent,
      pH value, and temperature on the extraction efficiency were investigated. (R)-o
      chloromandelic acid propyl ester was demonstrated to be an efficient chiral
      extractant for zopiclone resolution with a maximum enantioselectivity of 1.6.

PMID- 24123426
TI  - Apparent exchange rate imaging in anisotropic systems.
AB  - PURPOSE: Double-wave diffusion experiments offer the possibility of probing
      correlation between molecular diffusion at multiple time points. It has recently
      been shown that this technique is capable of measuring the exchange of water
      across cellular membranes. The aim of this study was to investigate the effect of
      macroscopic tissue anisotropy on the measurement of the apparent exchange rate
      (AXR) in multicompartment systems. METHODS: AXR data were collected from yeast
      and perfusion-fixated brain tissue at high angular resolution on a preclinical
      imaging system. The AXR was expanded for anisotropic systems by calculating
      scalar AXR values along the principal directions of the diffusion tensor.
      RESULTS: In yeast, both the AXR and diffusivity were rotational invariant,
      whereas in fixated brain tissue, the measured AXR was sensitive to the
      orientation of anisotropic structures. AXR, especially in white matter, was
      robustly estimated along the first and second principal directions of the
      diffusion tensor, but increasing noise was seen in the AXR estimates along the
      third principal direction of the diffusion tensor. CONCLUSION: Our results
      indicate that tissue anisotropy must be considered for AXR estimates in complex
      biological systems.

PMID- 24123427
TI  - Dynamic gadoxetate-enhanced MRI for the assessment of total and segmental liver
      function and volume in primary sclerosing cholangitis.
AB  - PURPOSE: To evaluate dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI)
      for the assessment of global and segmental liver volume and function in patients
      with primary sclerosing cholangitis (PSC), and to explore the heterogeneous
      distribution of liver function in this patient group. MATERIALS AND METHODS:
      Twelve patients with primary sclerosing cholangitis (PSC) and 20 healthy
      volunteers were examined using DHCE-MRI with Gd-EOB-DTPA. Segmental and total
      liver volume were calculated, and functional parameters (hepatic extraction
      fraction [HEF], input relative blood-flow [irBF], and mean transit time [MTT])
      were calculated in each liver voxel using deconvolutional analysis. In each study
      subject, and incongruence score (IS) was constructed to describe the mismatch
      between segmental function and volume. Among patients, the liver function
      parameters were correlated to bile duct obstruction and to established scoring
      models for liver disease. RESULTS: Liver function was significantly more
      heterogeneously distributed in the patient group (IS 1.0 versus 0.4). There were
      significant correlations between biliary obstruction and segmental functional
      parameters (HEF rho -0.24; irBF rho -0.45), and the Mayo risk score correlated
      significantly with the total liver extraction capacity of Gd-EOB-DTPA (rho 
      0.85). CONCLUSION: The study demonstrates a new method to quantify total and
      segmental liver function using DHCE-MRI in patients with PSC.

PMID- 24123428
TI  - Slitrk gene duplication and expression in the developing zebrafish nervous
      system.
AB  - BACKGROUND: The Slitrk family of leucine-rich repeat (LRR) transmembrane proteins
      bears structural similarity to the Slits and the Trk receptor families, which
      exert well-established roles in directing nervous system development. Slitrks are
      less well understood, although they are highly expressed in the developing
      vertebrate nervous system. Moreover, slitrk variants are associated with several
      sensory and neuropsychiatric disorders, including myopia, deafness, obsessive
      compulsive disorder (OCD), schizophrenia, and Tourette syndrome. Loss-of-function
      studies in mice show that Slitrks modulate neurite outgrowth and inhibitory
      synapse formation, although the molecular mechanisms of Slitrk function remain
      poorly characterized. RESULTS: As a prelude to examining the functional roles of
      Slitrks, we identified eight slitrk orthologs in zebrafish and observed that
      seven of the eight orthologs were actively transcribed in the nervous system at
      embryonic, larval, and adult stages. Similar to previous findings in mice and
      humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal
      expression patterns in the developing brain, retina, and spinal cord.
      CONCLUSIONS: Zebrafish express Slitrks in the developing central nervous system
      at times and locations important to neuronal morphogenesis and synaptogenesis.
      Future studies will use zebrafish as a convenient, cost-effective model organism
      to characterize the functional roles of Slitrks in nervous system development.

PMID- 24123429
TI  - Serum concentration of co-trimoxazole during a high-dosage regimen.
AB  - OBJECTIVES: Sulfamethoxazole and trimethoprim have been used for decades, yet
      high dosages are rarely reported. We aimed to measure blood concentrations of
      both molecules in this situation. METHODS: Between 2002 and 2010, 22 patients
      received two tablets of co-trimoxazole three times a day, equivalent to a daily
      dosage of 2400 mg of sulfamethoxazole and 480 mg of trimethoprim. The
      trimethoprim and sulfamethoxazole concentrations were determined 3 h after
      administration using ion-paired HPLC. RESULTS: In the presence of a negative
      control, which yielded no peaks at the retention times for trimethoprim and
      sulfamethoxazole, the mean +/- SD value for sulfamethoxazole concentration was
      161.01 +/- 69.154 mg/L and the mean +/- SD value for trimethoprim was 5.788 +/-
      2.74 mg/L. CONCLUSIONS: These concentrations are largely above the trimethoprim
      and sulfamethoxazole MIC distributions as well as the trimethoprim resistance
      clinical breakpoint (4 mg/L) reported by EUCAST in 2012 for most bacterial
      pathogens, including Gram-positive species such as Staphylococcus aureus. Our
      results support proposing a high-dosage regimen of co-trimoxazole as a suitable
      alternative for methicillin-resistant S. aureus infections.

PMID- 24123430
TI  - KPC-2-encoding plasmids from Escherichia coli and Klebsiella pneumoniae in
      Taiwan.
AB  - OBJECTIVES: Two plasmids carrying bla(KPC-2) isolated from carbapenem-resistant
      Escherichia coli (CR-EC) and carbapenem-resistant Klebsiella pneumoniae (CR-KP),
      respectively, were completely sequenced. The CR-KP strain was selected from an
      outbreak in 2012, and the CR-EC strain was the first blaKPC-2-carrying E. coli
      identified in the same carbapenem resistance monitoring programme in Taiwan.
      METHODS: Antimicrobial susceptibility tests, multilocus sequence typing (MLST)
      and the conjugal transfer of plasmids were performed. Complete sequencing of the
      plasmids was performed using a shotgun approach. RESULTS: The CR-EC and CR-KP
      strains in this study were determined to be ST410 and ST11, respectively, by
      MLST. From CR-EC, we identified a 145 kb conjugative plasmid that carries bla(KPC
      2), bla(CMY-2), bla(CTX-M-3) and bla(TEM-1). The plasmid is a chimera composed of
      three regions related to IncI, IncN and RepFIC replicons. From CR-KP, we
      identified an 86.5 kb plasmid, pKPC-LK30, which carries bla(KPC-2) and bla(SHV
      11). The plasmid is very similar to two bla(KPC-2)-carrying IncFII(K) plasmids,
      but lacks one of the replication origins and cannot conjugate. CONCLUSIONS: The
      differences in cross-species transferability of the two plasmids can be explained
      by genetic differences between their backbones and could have resulted in the
      confined bla(KPC-2)-carrying CR-KP outbreak in Taiwan. Plasmid pKPC-LKEc is the
      first bla(KPC-2)-carrying plasmid identified from CR-EC in Taiwan. With
      relatively high transferability it should be closely monitored.

PMID- 24123432
TI  - Farm assurance: FAWC fears loss of focus on welfare.

PMID- 24123431
TI  - Escherichia coli belonging to the worldwide emerging epidemic clonal group
      O25b/ST131: risk factors and clinical implications.
AB  - OBJECTIVES: Escherichia coli belonging to clonal group ST131 has emerged as a
      significant contributor to infection caused by antibiotic-resistant E. coli
      worldwide. We investigated the risk factors for infections caused by ST131 E.
      coli and their clinical implications. METHODS: One thousand and seventy-seven E.
      coli isolates were screened for ST131 by molecular methods. Risk factors for
      ST131 were investigated separately for patients with E. coli producing and not
      producing extended-spectrum beta-lactamases (ESBLs) in the Seville area, Spain.
      Multivariate analysis using logistic regression was performed. Patients with
      infections caused by ST131 and non-ST131 isolates were prospectively followed.
      RESULTS: Independent risk factors for non-ESBL-producing ST131 were female gender
      (OR: 1.94; 95% CI: 1.07-3.51), diabetes mellitus (OR: 2.17; 95% CI: 1.29-3.67),
      bedridden status (OR: 7.75; 95% CI: 0.70-85.07) and exposure to
      amoxicillin/clavulanate (OR: 2.07; 95% CI: 1.08-3.96) or fluoroquinolones (OR:
      2.48; 95% CI: 1.41-4.34). For ESBL-producing ST131, male gender was an
      independent risk factor (OR: 2.20; 95% CI: 0.94-5.11), while healthcare-related
      acquisition and exposure to any previous antibiotic were protective (OR: 0.30;
      95% CI: 0.13-0.71; and OR: 0.43; 95% CI: 0.19-1.00, respectively). Overall, the
      severity of sepsis, bacteraemia and mortality were similar among ST131 and non
      ST131 groups. The presence of typical factors predisposing to E. coli infection
      was more frequent in non-ESBL-producing ST131 than in controls (76% versus 57.2%,
      P = 0.005). CONCLUSIONS: Previous use of antibiotics selecting for ST131 isolates
      was the main modifiable risk factor for infections caused by these isolates. Our
      results also suggest that the clinical virulence of ST131 is not higher than that
      of other common E. coli causing infections.

PMID- 24123433
TI  - Welsh pilot scheme offers practical support on bovine TB.

PMID- 24123434
TI  - Small fall in new bovine TB breakdowns recorded in 2012.

PMID- 24123435
TI  - Could there be a link between seasonal canine illness and harvest mites?

PMID- 24123437
TI  - FVE clarifies its position on meat inspection proposals.

PMID- 24123445
TI  - MAP: helping farmers to make informed decisions.

PMID- 24123447
TI  - Pre-exposure vaccination against rabies: are we being left in the lurch?

PMID- 24123448
TI  - Emergency treatment of owned and wild animals.

PMID- 24123449
TI  - Emergency treatment of owned and wild animals.

PMID- 24123450
TI  - Husbandry and healthcare of pet and smallholder pigs.

PMID- 24123451
TI  - NSAIDs in the treatment of polyuria and polydipsia in dogs.

PMID- 24123452
TI  - Fine structure of bacterial adhesion to the epithelial cell membranes of the
      filiform papillae of tongue and palatine mucosa of rodents: a morphometric, TEM,
      and HRSEM study.
AB  - The palatine mucosa and filiform papillae of the dorsal tongue mucosae of rodents
      were examined using transmission electron microscopy (TEM) and high resolution
      scanning electron microscopy (HRSEM). In the HRSEM method, the samples were fixed
      in 2% osmium tetroxide, dehydrated in alcohol, critical point-dried, and coated
      with gold-palladium. In addition, the HRSEM technique was used for morphometric
      analysis (length, width, and length/width ratio of cocci and bacilli). For the
      TEM method, the tissues were fixed in modified Karnovsky solution (2.5%
      glutaraldehyde, 2% formalin in 0.1M sodium phosphate buffer, pH 7.4) and embedded
      in Spurr resin. The results demonstrated that there are thick polygonal
      keratinized epithelial cells where groups of bacteria are revealed in three
      dimensional images on the surface of filiform papillae in these animals. The
      bacterial membranes are randomly attached to the microplicae surface of
      epithelial cells. Morphometrics showed higher values of length and width of cocci
      in newborn (0 day) as compared to newborn (7 days) and adults animals, the
      bacilli showed no differences in these measurements. At high magnification, the
      TEM images revealed the presence of glycocalyx microfilaments that constitute a
      fine adhesion area between bacterial membranes and the membranes of epithelial
      microplicae cells. In conclusion, the present data revealed the fine fibrillar
      structures of bacteria that facilitate adhesion to the epithelial cell membranes
      of the oral cavity and morphometric changes in newborn (0 day) rats as compared
      with other periods.

PMID- 24123453
TI  - Leaf mesophyll conductance and leaf hydraulic conductance: an introduction to
      their measurement and coordination.
AB  - Two highly contrasting variables summarizing the efficiency of transport of
      materials within the leaf are recognized as playing central roles in determining
      gas exchange and plant performance. This paper summarizes current approaches for
      the measurement of mesophyll conductance to CO2 (g m) and leaf hydraulic
      conductance (K leaf) and addresses the physiological integration of these
      parameters. First, the most common methods to determine g m and K leaf are
      summarized. Next, novel data compilation is analysed, which indicates that,
      across diverse species, g m is strongly linked with gas exchange parameters such
      as net CO2 assimilation (A area) and stomatal conductance (g s), and with K leaf,
      independently of leaf vein length per leaf area. Based on their parallel
      responses to a number of environmental variables, this review proposes that g m
      is linked to the outside-xylem but not to the xylem component of K leaf. Further,
      a mechanistic hypothesis is proposed to explain the interactions among all these
      and other physiological parameters. Finally, the possibility of estimating g m
      based on this hypothesis was tested using a regression analysis and a neurofuzzy
      logic approach. These approaches enabled the estimation of g m of given species
      from K leaf and leaf mass per area, providing a higher predictive power than from
      either parameter alone. The possibility of estimating g m from measured K leaf or
      vice-versa would result in a rapid increase in available data. Studies in which g
      m, K leaf, and leaf mass per area are simultaneously determined are needed in
      order to confirm and strengthen predictive and explanatory models for these
      parameters and importantly improve resolution of the integrated hydraulic
      stomatal-photosynthetic system. 

PMID- 24123454
TI  - The evolution of autotrophy in relation to phosphorus requirement.
AB  - The evolution of autotrophy is considered in relation to the availability of
      phosphorus (P), the ultimate elemental resource limiting biological productivity
      through Earth's history. Work on microbes and plants is emphasized, dealing in
      turn with the main uses for P in cells, namely nucleic acids, phospholipids, and
      water-soluble low molecular mass phosphate esters plus metabolically active
      inorganic orthophosphate. There is a greater minimum gene number and minimum DNA
      content in autotrophic than in osmochemoorganotrophic archaea and bacteria, as
      well as a lower rate of biomass increase per unit P (P-use efficiency) in
      autotrophs than in osmochemoorganotrophs, in eukaryotes as well as bacteria. This
      may be due to the diversion of rRNA from producing proteins common to all
      organisms to producing highly expressed proteins specific to autotrophs. The P
      requirement for phospholipids is decreased in oxygenic photolithotrophs, and some
      anoxygenic photolithotrophs, by substituting galactolipids and sulpholipids for
      phospholipids in the photosynthetic, and some other, membranes. The six different
      autotrophic inorganic carbon assimilation pathways have varying requirements for
      low molecular mass water-soluble phosphate esters. In oxygenic photolithotrophs,
      there is no clear evidence of a different P requirement for growth in the absence
      (diffusive CO2 entry) relative to the presence of CO2-concentrating mechanisms
      (CCMs). P limitation increases the expression of crassulacean acid metabolism
      (CAM) in facultative CAM plants, decreases the extent of inorganic carbon
      accumulation in algae with CCMs, and (usually) their inorganic carbon affinity
      and the water-use efficiency of growth of terrestrial plants, and the light-use
      efficiency of photolithotrophs. 

PMID- 24123455
TI  - How do leaf veins influence the worldwide leaf economic spectrum? Review and
      synthesis.
AB  - Leaf vein traits are implicated in the determination of gas exchange rates and
      plant performance. These traits are increasingly considered as causal factors
      affecting the 'leaf economic spectrum' (LES), which includes the light-saturated
      rate of photosynthesis, dark respiration, foliar nitrogen concentration, leaf dry
      mass per area (LMA) and leaf longevity. This article reviews the support for two
      contrasting hypotheses regarding a key vein trait, vein length per unit leaf area
      (VLA). Recently, Blonder et al. (2011, 2013) proposed that vein traits, including
      VLA, can be described as the 'origin' of the LES by structurally determining LMA
      and leaf thickness, and thereby vein traits would predict LES traits according to
      specific equations. Careful re-examination of leaf anatomy, published datasets,
      and a newly compiled global database for diverse species did not support the
      'vein origin' hypothesis, and moreover showed that the apparent power of those
      equations to predict LES traits arose from circularity. This review provides a
      'flux trait network' hypothesis for the effects of vein traits on the LES and on
      plant performance, based on a synthesis of the previous literature. According to
      this hypothesis, VLA, while virtually independent of LMA, strongly influences
      hydraulic conductance, and thus stomatal conductance and photosynthetic rate. We
      also review (i) the specific physiological roles of VLA; (ii) the role of leaf
      major veins in influencing LES traits; and (iii) the role of VLA in determining
      photosynthetic rate per leaf dry mass and plant relative growth rate. A clear
      understanding of leaf vein traits provides a new perspective on plant function
      independently of the LES and can enhance the ability to explain and predict whole
      plant performance under dynamic conditions, with applications towards breeding
      improved crop varieties. 

PMID- 24123456
TI  - Diabetic Schwann cells suffer from nerve growth factor and neurotrophin-3
      underproduction and poor associability with axons.
AB  - Schwann cells (SCs) are integral to peripheral nerve biology, contributing to
      saltatory conduction along axons, nerve and axon development, and axonal
      regeneration. SCs also provide a microenvironment favoring neural regeneration
      partially due to production of several neurotrophic factors. Dysfunction of SCs
      may also play an important role in the pathogenesis of peripheral nerve diseases
      such as diabetic peripheral neuropathy where hyperglycemia is often considered
      pathogenic. In order to study the impact of diabetes mellitus (DM) upon the
      regenerative capacity of adult SCs, we investigated the differential production
      of the neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3) by
      SCs harvested from the sciatic nerves of murine models of type 1 DM
      (streptozotocin treated C57BL/6J mice) and type 2 DM (LepR(-/-) or db/db mice) or
      non-diabetic cohorts. In vitro, SCs from diabetic and control mice were
      maintained under similar hyperglycemic and euglycemic conditions respectively.
      Mature SCs from diabetic mice produced lower levels of NGF and NT3 under
      hyperglycemic conditions when compared to SCs in euglycemia. In addition, SCs
      from both DM and non-DM mice appear to be incapable of insulin production, but
      responded to exogenous insulin with greater proliferation and heightened
      myelination potentiation. Moreover, SCs from diabetic animals showed poorer
      association with co-cultured axons. Hyperglycemia had significant impact upon
      SCs, potentially contributing to the pathogenesis of diabetic peripheral
      neuropathy.

PMID- 24123457
TI  - CaRch1p does not functionally interact with the high-affinity Ca(2+) influx
      system (HACS) of Candida albicans.
AB  - The plasma membrane protein CaRch1p of Candida albicans, homologous to the human
      solute carrier protein SLC10A7, is involved in the regulation of calcium
      homeostasis. C. albicans cells lacking CaRCH1 are hypersensitive to high
      extracellular Ca(2+) concentrations and show increased tolerance to ketoconazole
      (KCZ). We assume a higher basal Ca(2+) influx in the rch1/rch1 mutant strain at
      low extracellular Ca(2+) concentrations, which is not detrimental to C. albicans
      cells but may be sufficient to activate calcineurin, finally resulting in an
      increased tolerance to KCZ. However, at 8 ug/ml KCZ plus 3 mm Ca(2+) the
      rch1/rch1 mutant and the wild-type strains showed identical growth. By further
      increasing the Ca(2+) concentration to 30 mm, this phenotype was completely
      reversed and the rch1/rch1 mutant strain became extremely sensitive to 8 ug/ml
      KCZ, probably due to synergistic toxic effects of Ca(2+) and KCZ under these
      conditions. Furthermore, we aimed to clarify whether CaRch1p interacts with the
      Cch1p component of the voltage-gated calcium influx channel Cch1p/Mid1p in C.
      albicans cells. As disruption of the two alleles of CCH1 in the rch1/rch1 mutant
      strain did not alter its hypersensitivity to high extracellular Ca(2+) , and as
      this phenotype was completely abolished by low amounts of Mg(2+) in the rch1/rch1
      mutant as well as in the cch1/cch1 rch1/rch1 double mutant, we conclude that
      CaRch1p is a functional component of the low-affinity calcium uptake system
      (LACS) system and does not functionally interact with Cch1p.

PMID- 24123458
TI  - Single-layer MoS(2) mechanical resonators.
AB  - Mechanical resonators are fabricated from freely suspended single-layer MoS2 .
      Their dynamics  have been studied by optical interferometry. These resonators
      behave as membranes with resonance frequencies in between 10 and 30 MHz and
      quality factors in between 16 and 109. We also demonstrate clear signatures of
      nonlinear resonance in these atomically thin resonators. 

PMID- 24123459
TI  - The choice of whether to participate in a phase I clinical trial: increasing the
      awareness of patients with cancer. An exploratory study.
AB  - OBJECTIVE: In a previous study, we found that patients who were offered the
      possibility of participation in a clinical trial had unexpressed concerns and
      fears that prevented them from making free or fully knowledgeable choices about
      their trial participation. In a selected population of patients who were offered
      participation in a phase I trial, we prospectively investigated whether a face-to
      face discussion about their unexpressed fears might lead to a more conscious
      decision about whether to accept/refuse participation in the trial. METHODS:
      After the presentation of the trial, a questionnaire was administered to assess
      the presence of specific fears. Before the patients decided whether to
      participate in the trial, they discussed any fears that they had; finally, the
      impact of the discussion on the patients' choice to participate was evaluated.
      RESULTS: The majority (86%) of the patients thought that physicians conduct
      clinical trials for scientific interest, 13% felt exploited as 'guinea pigs' and
      20% believed they were offered participation because they had no further hope for
      improvement. These existing fears were not elicited during the trial interview
      because the patients were themselves unaware of having them (28%) and because of
      fear of the doctors (3%). The possibility of discussing these fears was felt as
      an opportunity and made patients feel more conscious (92%) and freer (97%) when
      making their choice. CONCLUSIONS: Recognising and discussing misconceptions and
      fears, often unexpressed, make patients freer and more aware when facing the
      choice of whether or not ?to participate in a phase I clinical trial.

PMID- 24123460
TI  - DMSO-mediated ligand dissociation: renaissance for biological activity of N
      heterocyclic-[Ru(eta6-arene)Cl2] drug candidates.

PMID- 24123461
TI  - Preparation of well-defined poly(2-hydroxyethyl methacrylate) macromonomers via
      atom transfer radical polymerization.
AB  - A series of six near-monodisperse methacrylic macromonomers is prepared via atom
      transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate using a
      tertiary amine-functionalized initiator at 50  degrees C, followed by
      quaternization with excess 4-vinylbenzyl chloride at 20  degrees C. GPC analyses
      indicate polydispersities of around 1.20 and their mean degrees of polymerization
      (DP) range from 20 to 70, as judged by both (1) H NMR and UV spectroscopy. The
      former technique is more convenient but the latter proved more accurate for the
      higher DP values, provided that an appropriate model compound is utilized for
      calibration. Finally, these new macromonomers are used to prepare sterically
      stabilized polystyrene latexes with relatively narrow size distributions via
      alcoholic dispersion polymerization. 

PMID- 24123462
TI  - Organogelation-controlled topochemical [2+2] cycloaddition and morphological
      changes: from nanofiber to peculiar coaxial hollow toruloid-like nanostructures.
AB  - Novel amphiphilic molecules composed of naphthylacryl and L-glutamide moieties (1
      NA and 2-NA) have been designed and their organogel formation in various organic
      solvents as well as their self-assembled nanostructures have been investigated.
      Both compounds formed organogels in many organic solvents, ranging from nonpolar
      to polar, and self-assembled into essentially nanofiber structures, although some
      twist or belt structures could be observed in certain solvents. A gel of compound
      2-NA in ethanol initially self-assembled into nanofibers and then these were
      transformed into a family of coaxial hollow toruloid-like (CHTL) nanostructures
      under irradiation, in which various toroids and disks of different sizes were
      stacked coaxially. We have established that a topochemical [2+2] cycloaddition in
      the organogel triggers this transformation. When the gel was fabricated into
      xerogels in which no ethanol remained, such morphological changes could not
      happen. This might be the first report of an organogel, in which both organized
      nanofibers and solvent coexist, controlling a topochemical reaction as well as
      the self-assembled nanostructures formed. Due to the formation of the toruloid
      like nanostructures, the gel collapsed to a precipitate. However, upon heating
      this precipitate with ethanol, it redissolved and then formed a gel and self
      assembled into nanofibers once more. Thus, a reversible morphological
      transformation between nanofibers and an unprecedented series of toruloid-like
      nanostructures can be induced by alternately heating and irradiating the gel. 

PMID- 24123463
TI  - Treatment of eating disorders can not remain 'brainless': the case for brain
      directed treatments.

PMID- 24123464
TI  - The unified Huntington's Disease Rating Scale for advanced patients: validation
      and follow-up study.
AB  - The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline
      in patients at early and moderate stages of Huntington's disease (HD). In
      patients with advanced HD, floor effects hamper the evaluation, thus calling for
      an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to
      improve longitudinal assessment of patients at the advanced disease stage. Sixty
      nine patients with a Total Functional Capacity score <= 5 were recruited in
      France and the Netherlands. Among them, 45 patients were followed longitudinally
      (mean +/- standard deviation, 1.6 +/- 1.2 years) with the UHDRS-FAP; 30 patients
      also were assessed with the UHDRS. In cross-sectional analyses, the psychometric
      properties and inter-rater reliability of the scale were evaluated. Longitudinal
      analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP
      compared with the UHDRS. Internal consistency was higher for motor (0.84) and
      cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores.
      Inter-rater reliability was >= 0.88 for all scores. The somatic score, which was
      specific to the UHDRS-FAP, declined over time along with motor and cognitive
      performance on both scales. Although performance with the two scales was
      correlated, the UHDRS-FAP appeared to be more sensitive to change and was the
      only scale that detected decline in patients with a Total Functional Capacity
      score <= 1. Neither scale detected a significant decline in behavioral scores.
      The results indicate that the UHDRS-FAP is reliable and more sensitive to change
      than the original UHDRS for cognitive and motor domains. It offers items that are
      relevant for daily care. Behavioral scores tended to decline, but this may
      reflect the decline in patients' communicative abilities.

PMID- 24123465
TI  - Double inversion recovery MR imaging of the breast: efficacy in detection of
      breast cancer.
AB  - PURPOSE: To investigate the efficacy of the double inversion recovery sequence
      (DIR) in breast cancer detection. MATERIALS AND METHODS: Fifty-six patients with
      biopsy-proven breast cancers underwent preoperative breast MRI, including
      sagittal DIR and contrast-enhanced T1-weighted images (CE-T1WI). Twenty-four of
      the 56 patients additionally underwent sagittal T1WI and T2WI. The signal
      intensities of the lesion (L) and ipsilateral normal breast tissue (N) were
      measured. The lesion-to-normal ratio (LNR) was defined as LNR = 100(L-N)/N. We
      compared LNRs among the four sequences, and then assessed the differences of LNRs
      between CE-T1WI and DIR in each pathologic subgroup (IDC and non-IDC group).
      Multiple regression analysis was performed to identify predictors of the signal
      to-noise ratios (SNR) of the normal tissue or lesion and LNRs. RESULTS: The mean
      LNR did not differ significantly between DIR (58.65 +/- 71.55) and CE-T1WI (59.78
      +/-31.04), nor did the LNRs between DIR and CE-T1WI in the two subgroups. The
      LNRs of DIR did not differ significantly between the two subgroups (P = 0.247).
      The SNR of lesions in DIR was correlated with the intraductal component
      percentage (r(2) = 0.485, P = 0.037). CONCLUSION: DIR and CE-T1WI showed similar
      tumor detection efficacy, and DIR could complement dynamic MRI for detecting
      breast cancer without a contrast agent.

PMID- 24123466
TI  - A strongly emitting liquid-crystalline derivative of Y(3)N@C(80): bright and long
      lived near-IR luminescence from a charge transfer state.
AB  - Great balls of fire: C60 and Y3 N@C80 were connected to the same
      oligo(phenyleneethynylene) unit to investigate their structural and photophysical
      properties. NMR investigations revealed a fulleroid structure for the Y3 N@C80
      derivative, and both dyads gave rise to columnar phases with core-shell
      cylinders. The black and gray spheres represent the fullerene core units of the
      Y3 N@C80 derivative, which is an ideal candidate to be involved in energy and
      electron transfer processes. 

PMID- 24123467
TI  - Intramolecular isopeptide but not internal thioester bonds confer proteolytic and
      significant thermal stability to the S. pyogenes pilus adhesin Spy0125.
AB  - Streptococcus pyogenes and other Gram-positive bacterial pathogens present long
      macromolecular filaments known as pili on their surface that mediate adhesion and
      colonization. These pili are covalent polymers, assembled by sortases. Typically,
      they comprise a putative adhesin at their tip, a backbone subunit present in
      multiple copies and a basal subunit that is covalently anchored to the
      peptidoglycan layer of the cell surface. The crystal structures of pilin subunits
      revealed the presence of unusual covalent linkages in these proteins, including
      intramolecular isopeptide and internal thioester bonds. The intramolecular
      isopeptide bonds in backbone pilins are important for protein stability. Here,
      using both the wild-type protein and a set of mutants, we assessed the
      proteolytic and thermal stability of the S. pyogenes pilus tip adhesin Spy0125,
      in the presence and absence of its intramolecular isopeptide and internal
      thioester bonds. We also determined a crystal structure of the internal thioester
      bond variant Spy0125(Cys426Ala). We find that mutations in the intramolecular
      isopeptide bonds compromise the stability of Spy0125. Using limited proteolysis
      and thermal denaturation assays, we could separate the contribution of each
      intramolecular isopeptide bond to Spy0125 stability. In contrast, mutation in the
      internal thioester bond had a lesser effect on protein stability and the crystal
      structure is essentially identical to wild type. This work suggests that the
      internal thioester in Spy0125, although having a minor contributory role, is not
      required for protein stability and must have a different primary function, most
      likely mediating a covalent interaction with host cell ligands.

PMID- 24123469
TI  - N,N'-diamidocarbenes facilitate selective C-H insertions and transfer
      hydrogenations.

PMID- 24123468
TI  - Multi-label classification for colon cancer using histopathological images.
AB  - Colon cancer classification has a significant guidance value in clinical
      diagnoses and medical prognoses. The classification of colon cancers with high
      accuracy is the premise of efficient treatment. Our task is to build a system for
      colon cancer detection and classification based on slide histopathological
      images. Some former researches focus on single label classification. Through
      analyzing large amount of colon cancer images, we found that one image may
      contain cancer regions of multiple types. Therefore, we reformulated the task as
      multi-label problem. Four kinds of features (Color Histogram, Gray-Level Co
      occurrence Matrix, Histogram of Oriented Gradients and Euler number) were
      introduced to compose our discriminative feature set, extracted from our dataset
      that includes six single categories and four multi-label categories. In order to
      evaluate the performance and make comparison with our multi-label model, three
      commonly used multi-classification methods were designed in our experiment
      including one-against-all SVM (OAA), one-against-one SVM (OAO) and multi
      structure SVM. Four indicators (Precision, Recall, F-measure, and Accuracy) under
      3-fold cross-validation were used to validate the performance of our approach.
      Experiment results show that the precision, recall and F-measure of multi-label
      method as 73.7%, 68.2%, and 70.8% with all features, which are higher than the
      other three classifiers. These results demonstrate the effectiveness and
      efficiency of our method on colon histopathological images analysis.

PMID- 24123470
TI  - T1 mapping in the rat myocardium at 7 tesla using a modified CINE inversion
      recovery sequence.
AB  - PURPOSE: To evaluate the reproducibility and sensitivity of the modified CINE
      inversion recovery (mCINE-IR) acquisition on rats for measuring the myocardial T1
      at 7 Tesla. MATERIALS AND METHODS: The recently published mCINE-IR acquisition on
      humans was applied on rats for the first time, enabling the possibility of
      translational studies with an identical sequence. Simulations were used to study
      signal evolution and heart rate dependency. Gadolinium phantoms, a heart specimen
      and a healthy rat were used to study reproducibility. Two cryo-infarcted rats
      were scanned to measure late gadolinium enhancement (LGE). RESULTS: In the
      phantom reproducibility studies the T1 measurements had a maximum coefficient of
      variation (COV) of 1.3%. For the in vivo reproducibility the COV was below 5% in
      the anterior cardiac segments. In simulations with phantoms and specimens, a
      heart rate dependency of approximately 0.5 ms/bpm was present. The T1 maps of the
      cryo-infarcted rats showed a clear lowering of T1 in de LGE region. CONCLUSION:
      The results show that mCINE-IR is highly reproducible and that the sensitivity
      allows detecting T1 changes in the rat myocardium.

PMID- 24123471
TI  - Descriptive investigation of the recording of influenza vaccination details on
      The Health Information Network database.
AB  - BACKGROUND: The UK primary care databases are used in pharmacoepidemiology
      studies of vaccination type. We investigated vaccine recording and whether, and
      how, exposure to specific brands and batches can be identified. METHODS: Details
      of influenza vaccinations given in the 2010-2011 or 2011-2012 seasons were
      identified from coded and text fields in The Health Information Network UK
      primary care database. The proportion of people over 64 years of age vaccinated
      against influenza was compared with published regional rates. Searches for
      Fluvirin (Novartis Vaccines and Diagnostics GmbH, Marburg, Germany) batch numbers
      and name identified exposure to this specific vaccine. The recording of any brand
      name and batch number was described for a sample of 1000 vaccinations across 472
      practices. RESULTS: A total of 767 904 influenza vaccinations were identified
      during the 2010-2011 season and 784 518 in 2011-2012. Vaccination rates for
      people aged over 64 years were 75.6%, 80.9%, 78.4% and 71.9% in England, Northern
      Ireland, Scotland and Wales, respectively (2011-2012 season), compared with
      published figures of 74.0%, 77.0%, 76.2% and 67.7%. Rates were slightly lower in
      2010-2011 in both data sources. A Fluvirin brand was identified for 3.6% of all
      UK vaccinations but 26.2% of those in Scottish practices. Vaccination brand could
      be identified for 94.3% of the sample, 93.6% with a batch number. Batch number
      (98.5%) and brand name (50.3%) were most frequently recorded in an immunisation
      'batch' text field. CONCLUSION: Patients exposed to an influenza vaccine in
      primary care can be identified from The Health Information Network.
      Identification of brand or batch number requires a text search. Regional
      variation in brand of vaccine should be considered when estimating sample size.

PMID- 24123472
TI  - Pestalotiopens A and B: stereochemically challenging flexible sesquiterpene
      cyclopaldic acid hybrids from Pestalotiopsis sp.
AB  - From the endophytic fungus Pestalotiopsis sp. isolated from the leaves of the
      Chinese mangrove, Rhizophora mucronata, two novel hybrid sesquiterpene
      cyclopaldic acid metabolites with an unusual carbon skeleton, named
      pestalotiopens A and B, were obtained, together with the already known phytotoxin
      altiloxin B. Pestalotiopen B even contains a third, triketide-derived module. The
      constitutions and the absolute configurations of the new metabolites and of
      altiloxin B were unambiguously determined by a combination of spectroscopic
      methods and quantum-chemical optical-rotatory dispersion (ORD) and circular
      dichroism (CD) calculations. A biosynthetic pathway to pestalotiopens A and B is
      proposed with altiloxin B as one of the suggested precursors. Pestalotiopen A
      shows moderate antimicrobial activity against Enterococcus faecalis. 

PMID- 24123474
TI  - Polyhedral Au-Pd core-shell nanocrystals as highly spectrally responsive and
      reusable hydrogen sensors in aqueous solution.

PMID- 24123473
TI  - Satellite glial cell proliferation in the trigeminal ganglia after chronic
      constriction injury of the infraorbital nerve.
AB  - We have examined satellite glial cell (SGC) proliferation in trigeminal ganglia
      following chronic constriction injury of the infraorbital nerve. Using BrdU
      labeling combined with immunohistochemistry for SGC specific proteins we
      positively confirmed proliferating cells to be SGCs. Proliferation peaks at
      approximately 4 days after injury and dividing SGCs are preferentially located
      around neurons that are immunopositive for ATF-3, a marker of nerve injury. After
      nerve injury there is an increase GFAP expression in SGCs associated with both
      ATF-3 immunopositive and immunonegative neurons throughout the ganglia. SGCs also
      express the non-glial proteins, CD45 and CD163, which label resident macrophages
      and circulating leukocytes, respectively. In addition to SGCs, we found some
      Schwann cells, endothelial cells, resident macrophages, and circulating
      leukocytes were BrdU immunopositive.

PMID- 24123475
TI  - Functional connectivity changes differ in early and late-onset Alzheimer's
      disease.
AB  - At a similar stage, patients with early onset Alzheimer's disease (EOAD) have
      greater neocortical but less medial temporal lobe dysfunction and atrophy than
      the late-onset form of the disease (LOAD). Whether the organization of neural
      networks also differs has never been investigated. This study aims at
      characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in
      two groups of 14 patients matched for disease duration and severity, relative to
      age-matched controls. All subjects underwent an extensive neuropsychological
      assessment. Magnetic resonance imaging was used to quantify atrophy and resting
      state FC focusing on : the default mode network (DMN), found impaired in earlier
      studies on AD, and the anterior temporal network (ATN) and dorso-lateral
      prefrontal network (DLPFN), respectively involved in declarative memory and
      executive functions. Patterns of atrophy and cognitive impairment in EOAD and
      LOAD were in accordance with previous reports. FC within the DMN was similarly
      decreased in both EOAD and LOAD relative to controls. However, a double
      dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited
      decreased FC in the DLPFN and increased FC in the ATN relative to controls, while
      the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity
      correlated respectively with memory and executive performances, suggesting that
      increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale
      neural network changes in EOAD and LOAD endorse both common features and
      differences, probably related to a distinct distribution of pathological changes.

PMID- 24123476
TI  - Solvent-dependent truxene-based nanostructures.
AB  - Three truxene derivatives functionalized with alkyl chains, either attached
      directly or distanced by linking phenyl or ethynyl groups, self-assemble in
      solution and induce the gelation of different solvents in spite of not being
      endowed with groups able to establish strong directional interactions. A (1)H NMR
      study points to face-to-face alternating pi-stacked motifs at the origin of
      nucleation. Solvents play an important role in modulating the aggregation of
      these derivatives giving rise to fibrous or spherical superstructures. Analysis
      of the influence of different solvents on the morphology of the aggregates
      provides a better understanding of the various stages of the hierarchical self
      assembly. The way in which alkyl chains are attached to the central core also
      strongly affects the self-assembling properties and gelation ability of this
      series. Phenyl spacers present the highest association constants in solution and
      give rise to gelation in a broader range of solvents. This behavior has been
      rationalized by means of (1)H NMR spectroscopy, X-ray powder diffraction, SEM,
      and photophysical measurements. Interestingly, it was found that these compounds
      in the gel state exhibit unusual emission properties most likely arising from the
      formation of excimers, which evidences that pi-pi interactions also occur in the
      excited state.

PMID- 24123477
TI  - Temperature-dependent surface-enrichment effects of imidazolium-based ionic
      liquids.
AB  - We present the first systematic study of the influence of temperature on the
      degree of surface enrichment of 1-alkyl-3-methylimidazolium-based ionic liquids
      (ILs). Using angle-resolved X-ray photoelectron spectroscopy, we demonstrate that
      the degree of surface enrichment strongly decreases with increasing temperature
      for all the studied ILs. For ILs with the same cation, but different anions, [C8
      C1 Im]Br, [C8 C1 Im][TfO] and [C8 C1 Im][Tf2 N], no significant differences of
      the temperature-induced partial loss of surface enrichment are found.
      Measurements for [C4 C1 Im][TfO], [C8 C1 Im][TfO] and [C18 C1 Im][TfO] indicate a
      small effect of the chain length. For [C18 C1 Im][TfO], a continuous decrease of
      alkyl surface enrichment is found with increasing temperature, with no abrupt
      changes at the phase-transition temperature from the smectic A to the isotropic
      phase, indicating that the surface enrichment is not affected by this phase
      transition. 

PMID- 24123478
TI  - Expression of the de novo DNA methyltransferases (dnmt3 - dnmt8) during zebrafish
      lens development.
AB  - BACKGROUND: De novo DNA methylation is thought to be critical for cellular
      reprogramming during tissue differentiation and development. Little is known
      about the roles of de novo DNA methylation during eye development, and
      particularly during lens development. The lens is composed of lens epithelial
      (LE) and lens fiber (LF) cells, with proliferative LE cells giving rise to
      differentiated LFs at the "transition zone." Given the unique architecture and
      developmental program of the lens, and the involvement of de novo DNA methylation
      during differentiation events in other tissues, we sought to identify de novo DNA
      methyltransferases expressed in the zebrafish lens. RESULTS: Zebrafish possess
      six de novo DNA methyltransferase genes, dnmt3 - dnmt8. At 24 hr
      postfertilization (hpf), all six are expressed ubiquitously throughout the eye.
      By 72 hpf, dnmt3 and dnmt5 become restricted to cells of the retinal ciliary
      marginal zone (CMZ), dnmt4 and dnmt7 to cells of the CMZ and LE, and dnmt6 and
      dnmt8 to ganglion cells and cells of the inner nuclear layer of the retina.
      CONCLUSIONS: These data identify regions of the eye where de novo
      methyltransferases could mediate DNA methylation events during development.
      Overlapping expression domains also suggest functional redundancy within this
      gene family in the eye.

PMID- 24123479
TI  - Hollow polydimethylsiloxane beads with a porous structure for cell encapsulation.
AB  - Based on a water-in-oil-in-water emulsion system, porous and hollow
      polydimethylsiloxane (PDMS) beads containing cells using a simple fluidic device
      with three flow channels are fabricated. Poly(ethylene glycol) (PEG) in the PDMS
      oil phase is served as a porogen for pore development. The feasibility of the
      porous PDMS beads prepared with different PEG concentrations (10, 20, and 30 wt%)
      for cell encapsulation in terms of pore size, protein diffusion, and cell
      proliferation inside the PDMS beads is evaluated. The PDMS beads prepared with
      PEG 30 wt% are exhibited a highly porous structure and facilitated fast diffusion
      of protein from the core domain to the outer phase, eventually leading to
      enhanced cell proliferation. The results clearly indicate that hollow PDMS beads
      with a porous structure could provide a favorable microenvironment for cell
      survival due to the large porous structure. 

PMID- 24123480
TI  - Bis(amino)cyclopropenylidenes as organocatalysts for acyl anion and extended
      umpolung reactions.

PMID- 24123481
TI  - A high-yielding modular access to the lamellarins: synthesis of lamellarin G
      trimethyl ether, lamellarin eta and dihydrolamellarin eta.

PMID- 24123482
TI  - Mediators of physical exercise for improvement in cancer survivors' quality of
      life.
AB  - OBJECTIVE: Mediating mechanisms of a 12-week group-based exercise intervention on
      cancer survivors' quality of life (QoL) were examined to inform future exercise
      intervention development. METHODS: Two hundred nine cancer survivors >= 3 months
      posttreatment (57% breast cancer) aged 49.5 (+/- 10.4) years were assigned to
      physical exercise (n = 147) or wait-list control (n = 62). QoL, fatigue,
      emotional distress, physical activity, general self-efficacy and mastery were
      assessed at baseline and post-intervention using questionnaires. Path analysis
      was conducted using Mplus to explore whether improved physical activity, general
      self-efficacy and mastery mediated the effects of exercise on fatigue and
      distress and consequently QoL. RESULTS: The intervention was associated with
      increased physical activity (beta = 0.46, 95% confidence interval (CI) =
      0.14;0.59), general self-efficacy (beta = 2.41, 95%CI = 0.35;4.73), and mastery
      (beta = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct
      effect on fatigue (beta = -1.09, 95%CI = -2.12;0.01), and an indirect effect
      (beta = -0.54, 95%CI = -1.00;-0.21) via physical activity (beta = -0.29, 95%CI = 
      -0.64;-0.07) and general self-efficacy (beta = -0.25, 95%CI = -0.61;-0.05). The
      intervention had a borderline significant direct effect on reduced distress (beta
      = -1.32, 95%CI = -2.68;0.11), and a significant indirect effect via increased
      general self-efficacy and mastery (beta = -1.06, 95%CI = -1.89;-0.38). Reductions
      in fatigue (beta = -1.33, 95%CI =-1.85;-0.83) and distress (beta = -0.86, 95%CI =
      -1.25;-0.52) were associated with improved QoL. Further, increased physical
      activity was directly associated with improved QoL (beta = 3.37, 95%CI =
      1.01;5.54). CONCLUSION: The beneficial effect of group-based physical exercise on
      QoL was mediated by increased physical activity, general self-efficacy and
      mastery, and subsequent reductions in fatigue and distress. In addition to
      physical activity, future interventions should target self-efficacy and mastery.
      This may lead to reduced distress and fatigue, and consequently improved QoL of
      cancer survivors.

PMID- 24123483
TI  - Alexithymia-an independent risk factor for impulsive-compulsive disorders in
      Parkinson's disease.
AB  - Impulsive-compulsive disorders (ICDs) are frequent side effects of dopaminergic
      medication in Parkinson's disease (PD). Alexithymia, a personality trait
      characterized by difficulties identifying and describing feelings and an
      externally oriented thinking style, has been linked to various impulse-control
      problems in the general population. In PD, the prevalence of alexithymia is
      approximately twice as high as in the general population. However, whether
      alexithymia is associated with ICDs in PD is currently unknown. We examined the
      relationship between self-reported ICDs and alexithymia in a sample of 91 PD
      patients (89 on dopaminergic medication). Additional self-report measures
      assessed impulsivity, depression, anxiety, behavioral inhibition/approach, and
      emotion-regulation strategies. We observed that alexithymia, and particularly
      difficulty identifying feelings and difficulty describing feelings, was
      significantly correlated with ICDs, even when controlling for impulsivity,
      anxiety, and depression. In addition, a group analysis revealed that PD patients
      with clinical and moderate levels of alexithymia had significantly more ICDs than
      non-alexithymic patients, suggesting that even moderately high alexithymia levels
      increase the risk for ICDs in PD. Our results identify alexithymia as an
      independent risk factor for ICDs in PD. Thus, the inclusion of alexithymia in the
      neuropsychiatric assessment of patients with PD may help identify patients at
      risk for ICDs.

PMID- 24123484
TI  - Changes in oxycodone and heroin exposures in the National Poison Data System
      after introduction of extended-release oxycodone with abuse-deterrent
      characteristics.
AB  - PURPOSE: Abuse and misuse of prescription opioids are serious public health
      problems. Abuse-deterrent formulations are an intervention to balance risk
      mitigation with appropriate patient access. This study evaluated the effects of
      physicochemical barriers to crushing and dissolving on safety outcomes associated
      with extended-release oxycodone (ERO) tablets (OxyContin) using a national
      surveillance system of poison centers. Other single-entity (SE) oxycodone tablets
      and heroin were used as comparators and to assess substitution effects. METHODS:
      The National Poison Data System covering all US poison centers was used to
      measure changes in exposures in the year before versus the 2 years after
      introduction of reformulated ERO (7/2009-6/2010 vs 9/2010-9/2012). Outcomes
      included abuse, therapeutic errors affecting patients, and accidental exposures.
      RESULTS: After ERO reformulation, abuse exposures decreased 36% for ERO,
      increased 20% for other SE oxycodone, and increased 42% for heroin. Therapeutic
      errors affecting patients decreased 20% for ERO and increased 19% for other SE
      oxycodone. Accidental exposures decreased 39% for ERO, increased 21% for heroin,
      and remained unchanged for other SE oxycodone. During the study period, other
      interventions to reduce opioid abuse occurred, for example, educational and
      prescription monitoring programs. However, these have shown small effects and do
      not explain a drop for ERO exposures but not for other opioids. CONCLUSIONS:
      After ERO reformulation, calls to poison centers involving abuse, therapeutic
      errors affecting patients, and accidental exposures decreased for ERO, but not
      for comparator opioids. Abuse-deterrent formulations of opioid analgesics can
      reduce abuse, but switching to other accessible non abuse-deterrent opioids might
      occur.

PMID- 24123485
TI  - New head gradient coil design and construction techniques.
AB  - PURPOSE: To design and build a head insert gradient coil to use in conjunction
      with body gradients for superior imaging. MATERIALS AND METHODS: The use of the
      boundary element method to solve for a gradient coil wire pattern on an arbitrary
      surface allowed us to incorporate engineering changes into the electromagnetic
      design of a gradient coil directly. Improved wire pattern design was combined
      with robust manufacturing techniques and novel cooling methods. RESULTS: The
      finished coil had an efficiency of 0.15 mT/m/A in all three axes and allowed the
      imaging region to extend across the entire head and upper part of the neck.
      CONCLUSION: The ability to adapt an electromagnetic design to necessary changes
      from an engineering perspective leads to superior coil performance.

PMID- 24123486
TI  - A platinum(II) terpyridine metallogel with an L-valine-modified alkynyl ligand:
      interplay of Pt???Pt, pi-pi and hydrogen-bonding interactions.
AB  - A series of platinum(II) terpyridine complexes with L-valine-modified alkynyl
      ligands has been synthesized. A complex with an unsubstituted terpyridine and one
      valine unit on the alkynyl is shown to be capable of gel formation, which is in
      sharp contrast to the gelation properties of the corresponding organic
      counterparts. Upon sol-gel transition, a drastic color change from yellow to red
      is observed, which is indicative of the involvement of Pt???Pt interactions.
      Through the concentration- and temperature-dependent UV/Vis absorption, emission,
      circular dichroism, and (1) H NMR studies, the contribution of hydrogen bonding,
      Pt???Pt and pi-pi stacking interactions as driving forces for gelation have been
      established, and the importance of maintaining a delicate balance between
      different intermolecular forces has also been illustrated. 

PMID- 24123487
TI  - Acupuncture for vascular mild cognitive impairment: a systematic review of
      randomised controlled trials.
AB  - BACKGROUND: Vascular mild cognitive impairment (VMCI) is the most common type of
      vascular cognitive impairment induced by cerebrovascular disease. No effective
      medicines are currently available for VMCI. OBJECTIVE: To assess the
      effectiveness and safety of acupuncture for VMCI. METHODS: Seven electronic
      databases were searched for randomised controlled trials which investigated the
      effects of acupuncture compared with no treatment, placebo or conventional
      therapies on cognitive function or other clinical outcomes in patients with VMCI.
      The quality of the trials selected was evaluated according to the 'risk of bias'
      assessment provided by the Cochrane Handbook for Systematic Reviews of
      Interventions. RevMan V.5.1 software was employed for data analysis. RESULTS:
      Twelve trials with 691 participants were included. The methodological quality of
      all included trials was unclear and/or they had a high risk of bias. Meta
      analysis showed acupuncture in conjunction with other therapies could
      significantly improve Mini-Mental State Examination scores (mean difference 1.99,
      95% CI 1.09 to 2.88, random model, p<0.0001, 6 trials). No included trials
      mentioned any adverse events of the treatment. CONCLUSIONS: The current clinical
      evidence is not of sufficient quality for wider application of acupuncture to be
      recommended for the treatment of VMCI, and further large, rigorously designed
      trials are warranted.

PMID- 24123488
TI  - Detection of peptide-binding sites on protein surfaces: the first step toward the
      modeling and targeting of peptide-mediated interactions.
AB  - Peptide-mediated interactions, in which a short linear motif binds to a globular
      domain, play major roles in cellular regulation. An accurate structural model of
      this type of interaction is an excellent starting point for the characterization
      of the binding specificity of a given peptide-binding domain. A number of
      different protocols have recently been proposed for the accurate modeling of
      peptide-protein complex structures, given the structure of the protein receptor
      and the binding site on its surface. When no information about the peptide
      binding site(s) is a priori available, there is a need for new approaches to
      locate peptide-binding sites on the protein surface. While several approaches
      have been proposed for the general identification of ligand binding sites,
      peptides show very specific binding characteristics, and therefore, there is a
      need for robust and accurate approaches that are optimized for the prediction of
      peptide-binding sites. Here, we present PeptiMap, a protocol for the accurate
      mapping of peptide binding sites on protein structures. Our method is based on
      experimental evidence that peptide-binding sites also bind small organic
      molecules of various shapes and polarity. Using an adaptation of ab initio ligand
      binding site prediction based on fragment mapping (FTmap), we optimize a protocol
      that specifically takes into account peptide binding site characteristics. In a
      high-quality curated set of peptide-protein complex structures PeptiMap
      identifies for most the accurate site of peptide binding among the top ranked
      predictions. We anticipate that this protocol will significantly increase the
      number of accurate structural models of peptide-mediated interactions.

PMID- 24123489
TI  - Highly enantioselective dearomatizing formal [3+3] cycloaddition reactions of N
      acyliminopyridinium ylides with electrophilic enol carbene intermediates.

PMID- 24123490
TI  - Characterizing inorganic crystals grown on organic self-assembled bilayers with
      scanning probe and electron microscopies.
AB  - Combined microscopy techniques are used to establish the usability of phosphonic
      acid layers as promoters of hydroxyapatite (HAp) growth. Using spread coating,
      octadecylphosphonic acid (OPA) self-assembled bilayers are delivered to the thin
      natural oxide layer of a titanium film surface with no prior treatment. These
      bilayers aggregate two major advantages of phosphonic moieties to titanium
      surfaces: nucleation of hydroxyapatite crystals from ionic solution and affinity
      for both titanium oxide surface and HAp crystals. The functionalized substrates
      and bare titanium (control) samples are immersed in an aqueous solution
      containing calcium and phosphorus ions. Over a 4-week immersion time, OPA
      functionalized substrates present numerous large agglomerates of inorganic
      crystals, in contrast to control samples, with no significant amount of deposits.
      Initial sample characterization was performed with atomic force microscopy (AFM).
      Compositional and structural characterization of these agglomerates (using TEM,
      EDS, and electron diffraction), revealed that they are indeed HAp, the main
      component of the inorganic bone matrix.

PMID- 24123491
TI  - Evidence of reporting biases in voxel-based morphometry (VBM) studies of
      psychiatric and neurological disorders.
AB  - OBJECTIVES: To evaluate whether biases may influence the findings of whole-brain
      structural imaging literature. METHODS: Forty-seven whole-brain voxel-based meta
      analyses including voxel-based morphometry (VBM) studies in neuropsychiatric
      conditions were included, for a total of 324 individual VBM studies. The total
      sample size, the overall number of foci, and different moderators were extracted
      both at the level of the individual studies and at the level of the meta
      analyses. RESULTS: Sample size ranged from 12 to 545 (median n = 47) per VBM
      study. The median number of reported foci per study was six. VBM studies with
      larger sample sizes reported only slightly more abnormalities than smaller
      studies (2% increase in the number of foci per 10-patients increase in sample
      size). A similar pattern was seen in several analyses according to different
      moderator variables with some possible modulating evidence for the statistical
      threshold employed, publication year and number of coauthors. Whole-brain meta
      analyses (median sample size n = 534) found fewer foci (median = 3) than single
      studies and overall they showed no significant increase in the number of foci
      with increasing sample size. Meta-analyses with >=10 VBM studies reported a
      median of three foci and showed a significant increase with increasing sample
      size, while there was no relationship between sample size and number of foci
      (median = 5) in meta-analyses with <10 VBM studies. CONCLUSIONS: The number of
      foci reported in small VBM studies and even in meta-analyses with few studies may
      often be inflated. This picture is consistent with reporting biases affecting
      small studies.

PMID- 24123492
TI  - Astrocytes inhibit nitric oxide-dependent Ca(2+) dynamics in activated microglia:
      involvement of ATP released via pannexin 1 channels.
AB  - Under inflammatory conditions, microglia exhibit increased levels of free
      intracellular Ca(2+) and produce high amounts of nitric oxide (NO). However,
      whether NO, Ca(2+) dynamics, and gliotransmitter release are reciprocally
      modulated is not fully understood. More importantly, the effect of astrocytes in
      the potentiation or suppression of such signaling is unknown. Our aim was to
      address if astrocytes could regulate NO-dependent Ca(2+) dynamics and ATP release
      in LPS-stimulated microglia. Griess assays and Fura-2AM time-lapse fluorescence
      images of microglia revealed that LPS produced an increased basal [Ca(2+) ]i that
      depended on the sequential activation of iNOS, COXs, and EP1 receptor. TGFbeta1
      released by astrocytes inhibited the abovementioned responses and also abolished
      LPS-induced ATP release by microglia. Luciferin/luciferase assays and dye uptake
      experiments showed that release of ATP from LPS-stimulated microglia occurred via
      pannexin 1 (Panx1) channels, but not connexin 43 hemichannels. Moreover, in LPS
      stimulated microglia, exogenous ATP triggered activation of purinergic P2Y1
      receptors resulting in Ca(2+) release from intracellular stores. Interestingly,
      TGFbeta1 released by astrocytes inhibited ATP-induced Ca(2+) response in LPS
      stimulated microglia to that observed in control microglia. Finally, COX/EP1
      receptor signaling and activation of P2 receptors via ATP released through Panx1
      channels were critical for the increased NO production in LPS-stimulated
      microglia. Thus, Ca(2+) dynamics depended on the inflammatory profile of
      microglia and could be modulated by astrocytes. The understanding of mechanisms
      underlying glial cell regulatory crosstalk could contribute to the development of
      new treatments to reduce inflammatory cytotoxicity in several brain pathologies.

PMID- 24123493
TI  - Preparation of excitation-independent photoluminescent graphene quantum dots with
      visible-light excitation/emission for cell imaging.
AB  - We report the first pyrrole-ring surface-functionalized graphene quantum dots (p
      GQDs) prepared by a two-step hydrothermal approach under microwave irradiation in
      an ammonia medium. The most distinct feature of the functionalized GQDs is that
      both the excitation and emission wavelengths fall into the visible-light region.
      The p-GQDs are excited by visible light at lambda(ex) 490 nm (2.53 eV) to emit
      excitation-independent photoluminescence at a maximum wavelength of lambda(em)
      550 nm. This is thus far the longest emission wavelength reported for GQDs.
      Stable photoluminescence is achieved at pH 4-10 with an ionic strength of 1.2 mol
      L(-1) KCl. These features make the p-GQDs excellent probes for bio-imaging and
      bio-labeling, which is demonstrated by imaging live HeLa cells.

PMID- 24123495
TI  - Strong population structure and shallow mitochondrial phylogeny in the banded
      guitarfish, Zapteryx exasperata (Jordan y Gilbert, 1880), from the Northern
      Mexican Pacific.
AB  - The northern Mexican Pacific (NMP), the Gulf of California (GC), and Baja
      California have been recognized as an ecological and evolutionarily dynamic
      region having experienced significant tectonic and climatic changes leading to
      the diversification of terrestrial and marine biotas. Zapteryx exasperata is a
      predominant ray caught in the artisanal fisheries of the NMP. Morphometric and
      reproductive differences between rays from the GC and the Pacific coast of Baja
      California (PCBC) regions suggest the presence of distinct populations. We
      investigate whether this distinction correlates with differences in genetic
      diversity and differentiation using sequences of the mitochondrial nicotinamide
      adenine dinucleotide dehydrogenase subunit 2 (ND2) gene and the noncoding control
      region (CR) in 63 specimens. Contrary to our expectations, ND2 bore significantly
      more diversity (h = 0.76) than CR (h = 0.39). Geographic patterns of diversity of
      CR were opposite to those of ND2, with GC being significantly less (ND2) and more
      (CR) diverse than PCBC. The diversity of concatenated haplotypes was high (h =
      0.84). Low nucleotide diversity suggests the recent coancestry of haplotypes.
      Marked genetic structure (Phist = 0.23, P < 0.0001) revealed the existence of
      reproductive isolation and limited matrilineal gene flow between GC and PCBC,
      which correlates with their phenotypic distinction. These results suggest the
      influence of factors such as female reproductive philopatry, and ecological or
      historical vicariant barriers to gene flow. Our results point to the existence of
      a distinct management unit of banded guitarfish in each region, and add to the
      increasing evidence attesting to the diversifying nature of this evolutionarily
      dynamic region. 

PMID- 24123494
TI  - Extending RosettaDock with water, sugar, and pH for prediction of complex
      structures and affinities for CAPRI rounds 20-27.
AB  - Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided
      a testing platform for computational methods designed to address a wide range of
      challenges. The diverse targets drove the creation of and new combinations of
      computational tools. In this study, RosettaDock and other novel Rosetta protocols
      were used to successfully predict four of the 10 blind targets. For example, for
      DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand
      were used to predict the positions of water molecules at the interface,
      recovering 46% of the native water-mediated contacts. For alpha-repeat Rep4-Rep2
      and g-type lysozyme-PliG inhibitor complexes, homology models were built and
      standard and pH-sensitive docking algorithms were used to generate structures
      with interface RMSD values of 3.3 A and 2.0 A, respectively. A novel flexible
      sugar-protein docking protocol was also developed and used for structure
      prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the
      native contacts. Challenges remain in the generation of accurate homology models
      for protein mutants and sampling during global docking. On proteins designed to
      bind influenza hemagglutinin, only about half of the mutations were identified
      that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the
      xylanase complex involving homology modeling and multidomain docking pushed the
      limits of global conformational sampling and did not result in any successful
      prediction. The diversity of problems at hand requires computational algorithms
      to be versatile; the recent additions to the Rosetta suite expand the
      capabilities to encompass more biologically realistic docking problems.

PMID- 24123496
TI  - Global warming enhances sulphide stress in a key seagrass species (NW
      Mediterranean).
AB  - The build-up of sulphide concentrations in sediments, resulting from high inputs
      of organic matter and the mineralization through sulphate reduction, can be
      lethal to the benthos. Sulphate reduction is temperature dependent, thus global
      warming may contribute to even higher sulphide concentrations and benthos
      mortality. The seagrass Posidonia oceanica is very sensitive to sulphide stress.
      Hence, if concentrations build up with global warming, this key Mediterranean
      species could be seriously endangered. An 8-year monitoring of daily seawater
      temperature, the sulphur isotopic signatures of water (delta(34)S(water)),
      sediment (delta(34)SCRS ) and P. oceanica leaf tissue (delta(34)S(leaves)), along
      with total sulphur in leaves (TS(leaves)) and annual net population growth along
      the coast of the Balearic archipelago (Western Mediterranean) allowed us to
      determine if warming triggers P. oceanica sulphide stress and constrains seagrass
      survival. From the isotopic S signatures, we estimated sulphide intrusion into
      the leaves (F(sulphide)) and sulphur incorporation into the leaves from
      sedimentary sulphides (SS(leaves)). We observed lower delta(34)S(leaves), higher
      F(sulphide) and SS(leaves) coinciding with a 6-year period when two heat waves
      were recorded. Warming triggered sulphide stress as evidenced by the negative
      temperature dependence of delta(34)S(leaves) and the positive one of F(sulphide),
      TS(leaves) and SS(leaves). Lower P. oceanica net population growth rates were
      directly related to higher contents of TS(leaves). At equivalent annual maximum
      sea surface water temperature (SST(max)), deep meadows were less affected by
      sulphide intrusion than shallow ones. Thus, water depth acts as a protecting
      mechanism against sulphide intrusion. However, water depth would be insufficient
      to buffer seagrass sulphide stress triggered by Mediterranean seawater summer
      temperatures projected for the end of the 21st century even under scenarios of
      moderate greenhouse gas emissions, A1B. Mediterranean warming, therefore, is
      expected to enhance P. oceanica sulphide stress, and thus compromise the survival
      of this key habitat along its entire depth distribution range.

PMID- 24123497
TI  - Semi-transparent polymer solar cells with excellent sub-bandgap transmission for
      third generation photovoltaics.
AB  - Semi-transparent organic photovoltaics are of interest for a variety of
      photovoltaic applications, including solar windows and hybrid tandem
      photovoltaics. The figure shows a photograph of our semi-transparent solar cell,
      which has a power conversion efficiency of 5.0%, with an above bandgap
      transmission of 34% and a sub-bandgap transmission of 81%.

PMID- 24123498
TI  - Interactions of imidazolium-based ionic liquids with oxide surfaces controlled by
      alkyl chain functionalization.
AB  - From a different angle: Thin films of functionalized ionic liquids are deposited
      on cerium oxides following a surface science approach. The functionalization of
      the alkyl chain changes its orientation with respect to the surface plane from
      normal to parallel. This then leads to a different surface chemistry at higher
      temperatures. 

PMID- 24123499
TI  - Directing-group-assisted copper-catalyzed olefinic trifluoromethylation of
      electron-deficient alkenes.
AB  - Assistance provided: The directing group in the title reaction not only activates
      the substrates but also allows the stereospecific formation of cis
      trifluoromethylated products. The reaction is operationally simple and tolerates
      a wide variety of functional groups, thus providing an efficient method for the
      stereoselective synthesis of beta-CF3 -functionalized acrylamide derivatives. 

PMID- 24123500
TI  - Cortical gyrification reductions and subcortical atrophy in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder
      characterized by both motor and non-motor symptoms. Previous morphometric studies
      of PD were mainly conducted by measuring gray matter volume and cortical
      thickness, and little attention has been paid to the morphology of the cortical
      surface. METHODS: Using a surface-based local gyrification index (lGI), this
      study compared the cortical gyrification patterns of 37 PD patients and 34
      matched healthy controls. Volumetric analyses also were performed on the
      subcortical structures. RESULTS: Compared with the control group, patients with
      PD had significantly reduced cortical gyrification in multiple brain regions,
      which the authors speculated were associated with disruptions in white matter
      connectivity and suboptimal intracortical organization. In addition, subcortical
      volume atrophy was identified in the bilateral hippocampus and bilateral caudate
      of the patients with PD. CONCLUSIONS: Further studies are needed to identify the
      clinical correlates of the structural abnormalities observed in PD.

PMID- 24123501
TI  - Induced pluripotent stem cells from goat fibroblasts.
AB  - Embryonic stem cells (ESCs) are a powerful model for genetic engineering,
      studying developmental biology, and modeling disease. To date, ESCs have been
      established from the mouse (Evans and Kaufman, 1981, Nature 292:154-156), non
      human primates (Thomson et al., , Proc Nat Acad Sci USA 92:7844-7848), humans
      (Thomson et al., 1998, Science 282:1145-1147), and rats (Buehr et al., , Cell
      135:1287-1298); however, the derivation of ESCs from domesticated ungulates such
      as goats, sheep, cattle, and pigs have not been successful. Alternatively,
      induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic
      cells with several combinations of genes encoding transcription factors (OCT3/4,
      SOX2, KLF4, cMYC, LIN28, and NANOG). To date, iPSCs have been isolated from
      various species, but only limited information is available regarding goat iPSCs
      (Ren et al., 2011, Cell Res 21:849-853). The objectives of this study were to
      generate goat iPSCs from fetal goat primary ear fibroblasts using lentiviral
      transduction of four human transcription factors: OCT4, SOX2, KLF4, and cMYC. The
      goat iPSCs were successfully generated by co-culture with mitomycin C-treated
      mouse embryonic fibroblasts using medium supplemented with knockout serum
      replacement and human basic fibroblast growth factor. The goat iPSCs colonies are
      flat, compact, and closely resemble human iPSCs. They have a normal karyotype;
      stain positive for alkaline phosphatase, OCT4, and NANOG; express endogenous
      pluripotency genes (OCT4, SOX2, cMYC, and NANOG); and can spontaneously
      differentiate into three germ layers in vitro and in vivo.

PMID- 24123502
TI  - Emotions and social relationships for breast and gynecologic patients: a
      qualitative study of coping with recurrence.
AB  - BACKGROUND: In contrast to the large literature on patients' coping with an
      initial diagnosis of cancer, there have been few quantitative or qualitative
      studies of patients coping with recurrence. A qualitative study was undertaken to
      aid in the development of a tailored intervention for these patients. METHODS:
      Individuals (N=35) receiving follow-up care for recurrent breast or gynecologic
      cancer at a university-affiliated cancer center participated in an individual or
      a group interview. Transcripts of interviews were analyzed using a coding format
      with two areas of emphasis. First, we focused on patients' emotions, as there is
      specificity between emotions and the corresponding ways in which individuals
      choose to manage them. Secondly, we considered the patients' social environments
      and relationships, as they too appear key in the adjustment to, and survival
      from, cancer. RESULTS: Patients identified notable differences in their responses
      to an initial diagnosis of cancer and their current ones to recurrence, including
      the following: (i) depressive symptoms being problematic; (ii) with the passing
      years and the women's own aging, there is shrinkage in the size of social
      networks; and (iii) additional losses come from social support erosion, arising
      from a) intentional distancing by social contacts, b) friends and family not
      understanding that cancer recurrence is a chronic illness, and/or c) patients
      stemming their support requests across time. CONCLUSION: The contribution of
      these findings to the selection of intervention strategies is discussed.

PMID- 24123503
TI  - Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of
      molecular diversity and utility.
AB  - Diversity-oriented biosynthesis of a library of antimycin-like compounds (380
      altogether) was accomplished by using multiplex combinatorial biosynthesis. The
      core strategy depends on the use of combinatorial chemistry at different
      biosynthetic stages. This approach is applicable for the diversification of
      polyketides, nonribosomal peptides, and the hybrids that share a similar
      biosynthetic logic. 

PMID- 24123504
TI  - MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging
      (SWI) to visualize calcifications in ex vivo swine brain.
AB  - PURPOSE: To present the use of MR-acoustic radiation force imaging (MR-ARFI) and
      susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo
      brain tissue as a planning indicator for MR-guided focused ultrasound (MRgFUS).
      MATERIALS AND METHODS: Calcifications were implanted in ex vivo swine brain and
      imaged using SWI, MR-ARFI, and computed tomography (CT). SWI-filtered phase
      images used 3D gradient recalled echo (GRE) images with a Fourier-based
      unwrapping algorithm. The MR-ARFI pulse sequence used a 2DFT spin-echo with
      repeated bipolar encoding gradients in the direction of the longitudinal
      ultrasound beam. MR-ARFI interrogations scanned a subregion (14 * 10 * 12 mm) of
      the brain surrounding the calcification. They were combined into a single
      displacement weighted map, using the sum of squares method. Calcification size
      estimates were based on image profiles plotted along the +/-x and +/-z direction,
      at the full-width half-maximum. RESULTS: Both MR-ARFI and SWI were able to
      visualize the calcifications. The contrast ratio was 150 for CT, 12 for SWI, and
      12 for MR-ARFI. Profile measures were 1.35 * 1.28 mm on CT, 1.24 * 1.73 mm on
      SWI, and 2.45 * 3.02 mm on MR-ARFI. MR-ARFI displacement showed a linear increase
      with acoustic power (20-80 W), and also increased with calcification size.
      CONCLUSION: The use of SWI-filtered phase and MR-ARFI have the potential to
      provide a clinical indicator of calcification relevance in the planning of a
      transcranial MRgFUS treatment.

PMID- 24123506
TI  - Prescribing of antipsychotic drugs in patients with dementia: a comparison with
      age-matched and sex-matched non-demented controls.
AB  - PURPOSE: Since the beginning of the 21st century, serious adverse events and an
      increased risk of mortality have been documented in patients with dementia
      treated with antipsychotics. The aim of this study was to assess antipsychotic
      prescribing in patients with incident dementia compared with a non-demented
      control group. METHODS: We analysed the claims data of a German health insurance
      company for incident dementia patients and age-matched and sex-matched non
      demented controls aged 65 years and older in 2004 to 2006. The data were used to
      analyse the prescribing patterns of antipsychotics in the year of dementia
      incidence. We estimated odds ratios stratified by age, sex, care setting and care
      dependence and in a multivariate logistic regression. RESULTS: The 1848 patients
      with and 7385 persons without dementia were on average 78.8 years old (standard
      deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients
      received antipsychotics compared with 4.3% of the controls (ORcrude : 7.61;
      95%CI: 6.52-8.87). An increase in care level, age, female gender and living in a
      nursing home is associated with a considerably higher prevalence of at least one
      prescription for antipsychotics. After adjusting for all these variables, a
      significant influence of age could no longer be found. CONCLUSIONS: The results
      show that antipsychotics play an important role in dementia care-despite the risk
      of adverse events. Further research is needed with regard to safe pharmacological
      and non-pharmacological approaches for the behavioural and psychological symptoms
      of dementia in this vulnerable group.

PMID- 24123505
TI  - Silymarin improves vascular function of aged ovariectomized rats.
AB  - Both aging and estrogen depletion lead to endothelial dysfunction, which is the
      main reason of many cardiovascular diseases. Previous reports have shown that
      cell protective effect of silymarin (SM) depends on its antioxidant and
      phytoestrogenic properties. We investigated the effect of SM on vascular
      stiffness of aged menopausal rats and the involvement of estrogenic activity in
      this effect. Isolated rat aortas were obtained from 22-month-old rats, after 18
      months of ovariectomy (OVX) follow-up. Each ring was incubated in tissue bath
      either with SM (50 mg/L) and 17beta-estradiol (10 MUM, E2) or in the presence of
      SM/fulvestrant (50 mg/L, 10 MUM). Endothelium-intact rings were precontracted
      with phenylephrine (0.001-30 MUM) or high potassium (40 mM); endothelium
      dependent/independent relaxant responses were obtained using acetylcholine (0.001
      30 MUM) and sodium nitroprusside (0.0001-3 MUM), respectively. While
      phenylephrine sensitivity was significantly increased in OVX rats, relaxations
      were significantly less in aged OVX rats compared with young rats. In spite of
      the presence of estrogen antagonist, immediate SM treatment restored the
      endothelial function and vascular tone better than estrogen replacement.
      Additionally, as a complementary and alternative medicine, it does not cause
      estrogenic side effects when taken acutely.

PMID- 24123507
TI  - Irx4 identifies a chamber-specific cell population that contributes to
      ventricular myocardium development.
AB  - BACKGROUND: The ventricular myocardium is the most prominent layer of the heart,
      and the most important for mediating cardiac physiology. Although the ventricular
      myocardium is critical for heart function, the cellular hierarchy responsible for
      ventricle-specific myocardium development remains unresolved. RESULTS: To
      determine the pattern and time course of ventricular myocardium development, we
      investigated IRX4 protein expression, which has not been previously reported. We
      identified IRX4+ cells in the cardiac crescent, and these cells were positive for
      markers of the first or second heart fields. From the onset of chamber formation,
      IRX4+ cells were restricted to the ventricular myocardium. This expression
      pattern persisted into adulthood. Of interest, we observed that IRX4 exhibits
      developmentally regulated dynamic intracellular localization. Throughout prenatal
      cardiogenesis, and up to postnatal day 4, IRX4 was detected in the cytoplasm of
      ventricular myocytes. However, between postnatal days 5-6, IRX4 translocated to
      the nucleus of ventricular myocytes. CONCLUSIONS: Given the ventricle-specific
      expression of Irx4 in later stages of heart development, we hypothesize that
      IRX4+ cells in the cardiac crescent represent the earliest cell population in the
      cellular hierarchy underlying ventricular myocardium development.

PMID- 24123509
TI  - Diversity-oriented synthesis of hydrazine-derived compounds from amino
      isocyanates generated in situ.

PMID- 24123510
TI  - A new chiral binaphthalene-based fluorescence polymer sensor for the highly
      enantioselective recognition of phenylalaninol.
AB  - A new (S)-binaphthalene-based polymer (P-1) was synthesized by the polymerization
      of 5,5'-((2,5-dibutoxy-1,4-phenylene)bis(ethyne-2,1-diyl))bis(2-hydroxy-3
      (piperidin-1-ylmethyl) benzaldehyde (M-1) with (S)-2,2'-dimethoxy-(1,1'
      binaphthalene)-3,3'-diamine (M-2) through the formation of a Schiff base; the
      corresponding chiral polymer (P-2) could be obtained by the reduction of polymer
      P-1 with NaBH4 . Chiral polymer P-1 exhibited a remarkable "turn-on" fluorescence
      enhancement response towards (D)-phenylalaninol and excellent enantioselective
      recognition behavior with enantiomeric fluorescence difference ratios (ef) as
      high as 8.99. More importantly, chiral polymer P-1 displays a bright blue
      fluorescence color change upon the addition of (D)-phenylalaninol under a
      commercially available UV lamp, which can be clearly observed by the naked eye.
      On the contrary, chiral polymer P-2 showed weaker enantioselective fluorescence
      ability towards the enantiomers of phenylalaninol. 

PMID- 24123508
TI  - Pattern classification of response inhibition in ADHD: toward the development of
      neurobiological markers for ADHD.
AB  - The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on
      subjective measures despite evidence for multisystemic structural and functional
      deficits. ADHD patients have consistent neurofunctional deficits in motor
      response inhibition. The aim of this study was to apply pattern classification to
      task-based functional magnetic resonance imaging (fMRI) of inhibition, to
      accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and
      thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI
      data were analyzed with Gaussian process classifiers (GPC), a machine learning
      approach, to predict individual ADHD diagnosis based on task-based activation
      patterns. Traditional univariate case-control analyses were also performed to
      replicate previous findings in a relatively large dataset. The pattern of brain
      activation correctly classified up to 90% of patients and 63% of controls,
      achieving an overall classification accuracy of 77%. The regions of the
      discriminative network most predictive of controls included later developing
      lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition,
      while regions most predictive of ADHD were in earlier developing ventromedial
      fronto-limbic regions, which furthermore correlated with symptom severity.
      Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral
      prefrontal, striatal, and temporo-parietal regions that overlapped with areas
      predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We
      show that significant individual classification of ADHD patients of 77% can be
      achieved using whole brain pattern analysis of task-based fMRI inhibition data,
      suggesting that multivariate pattern recognition analyses of inhibition networks
      can provide objective diagnostic neuroimaging biomarkers of ADHD.

PMID- 24123511
TI  - A systematic study of fluorescence-based detection of nitroexplosives and other
      aromatics in the vapor phase by microporous metal-organic frameworks.
AB  - A systematic study is conducted on four microporous metal-organic framework
      compounds built on similar ligands but different structures, namely
      [Zn3(bpdc)3(bpy)].4DMF.H2O (1), [Zn3(bpdc)3(2,2'dmbpy)].4DMF.H2O (2),
      [Zn2(bpdc)2(bpe)].2DMF (3), and [Zn(bpdc)(bpe)].DMF (4) (bpdc=4,4'
      biphenyldicarboxylate; bpy=4,4'-bipyridine; 2,2'dmbpy=2,2'-dimethyl
      4,4'bipyridine; bpe=1,2-bis(4-pyridyl)ethane; DMF=N,N'-dimethylformamide) to
      investigate their photoluminescence properties and sensing/detection behavior
      upon exposure to vapors of various aromatic molecules (analytes) including
      nitroaromatic explosives. The results show that all four compounds are capable of
      detecting these molecules in the vapor phase through fluorescence quenching or
      enhancement. Both electrochemical measurements and theoretical calculations are
      performed to analyze the analyte-MOF interactions, to explain the difference in
      signal response by different analytes, and to understand the mechanism of
      fluorescence quenching or enhancement observed in these systems. Interestingly,
      compound 3 also shows an emission frequency shift when exposed to benzene (BZ),
      chlorobenzene (ClBZ), and toluene (TO), which provides an additional variable for
      the identification of different analytes in the same category.

PMID- 24123512
TI  - Volume-outcome associations in head and neck cancer treatment: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Because of the relative rarity of head and neck malignancies and
      their complex treatment, some groups have advocated for regionalized care.
      Studies comparing high- and low-volume centers have demonstrated mixed results.
      METHODS: We conducted a systematic review using MEDLINE and EMBASE including all
      studies examining a volume-outcome relationship in the treatment of patients with
      head and neck cancer with meta-analysis for long-term survival results. RESULTS:
      Seventeen studies were identified. Meta-analysis was performed for studies that
      assessed long-term survival. High-volume hospitals (5 studies; hazard ratio [HR],
      0.886; 95% confidence interval [CI], 0.820-0.956) and high-volume surgeons (2
      studies; HR, 0.767; 95% CI, 0.641-0.919) have better overall survival than low
      volume hospitals and surgeons, respectively. CONCLUSION: Volume-outcome
      associations exist for head and neck oncologic procedures, although this has not
      been fully investigated for salivary gland malignancies. Future quality of care
      studies in head and neck oncology should focus on processes of care, which may
      explain this relationship.

PMID- 24123513
TI  - Confocal laser scanning microscopic analysis of ectopic sublingual gland-like
      tissue inside the hamster submandibular gland.
AB  - Based on its histochemical properties, the secretory portion of the hamster
      submandibular gland has been classified as seromucous cells. The presence of
      endogenous peroxidase (PO) reaction was shown in the nuclear envelope, cisternae
      of endoplasmic reticulum and Golgi apparatus. The 3,3'-diaminobenzidene,
      tetrahydrochloride (DAB) method revealed bipartite secretory granules containing
      a PO-positive dense core surrounded by a less dense halo in these cells. In the
      present investigation, serous and mucous-like cells were found in resin-embedded
      semi-thin sections of the DAB-reacted hamster submandibular gland. These sections
      were already on glass slides for routine light microscopic observations,
      therefore electron microscopic analysis could be unrealizable. We then used
      reflectance-mode confocal laser scanning microscopy to visualize additional sites
      of PO activity as detected in these sections. Using this approach, we found
      mucous cells with PO activity-negative secretory granules and seromucous cells
      with PO activity-positive spot-like secretory granules of the regular sublingual
      gland most frequently adjacent to the serous cells with typical electron-dense
      secretory granules. These cells clearly differ from the seromucous cells with
      bipartite secretory granules and the granular duct cells with typical electron
      dense secretory granules of the hamster submandibular gland. Additionally,
      secretory endpieces of the ectopic sublingual gland-like tissue empty into the
      duct of the hamster submandibular gland lobule. Thus, our findings suggest that a
      mass of sublingual gland tissue extends into the hamster submandibular gland
      during its development, and PO may be synthesized and secreted into the same
      duct.

PMID- 24123514
TI  - An integrated computational approach for metabolic flux analysis coupled with
      inference of tandem-MS collisional fragments.
AB  - MOTIVATION: Metabolic flux analysis (MFA) is a commonly used approach for
      quantifying metabolic fluxes based on tracking isotope labeling of metabolite
      within cells. Tandem mass-spectrometry (MS/MS) has been recently shown to be
      especially useful for MFA by providing rich information on metabolite positional
      labeling, measuring isotopic labeling patterns of collisional fragments. However,
      a major limitation in this approach is the requirement that the positional origin
      of atoms in a collisional fragment would be known a priori, which in many cases
      is difficult to determine. RESULTS: Here we show that MS/MS data could also be
      used to improve flux inference even when the positional origin of fragments is
      unknown. We develop a novel method, metabolic flux analysis/unknown fragments,
      that extends on standard MFA and jointly searches for the most likely metabolic
      fluxes together with the most plausible position of collisional fragments that
      would optimally match measured MS/MS data. MFA/UF is shown to markedly improve
      flux prediction accuracy in a simulation model of gluconeogenesis and using
      experimental MS/MS data in Bacillus subtilis.

PMID- 24123515
TI  - Inhibition of P2X4 function by P2Y6 UDP receptors in microglia.
AB  - ATP-gated P2X4 receptor channels expressed in spinal microglia actively
      participate in central sensitization, making their functional regulation a key
      process in chronic pain pathologies. P2Y6 metabotropic Gq -coupled receptors,
      also expressed in microglia, are involved in the initial response to nerve
      injury, triggering phagocytosis upon activation by UDP. It has been reported
      recently that expression of both P2X4 and P2Y6 is upregulated in activated
      microglia following nerve injury. We show here, in resting as well as LPS
      activated primary microglia, that P2Y6 decreases P2X4-mediated calcium entry and
      inhibits the dilation of P2X4 channels into a large-conductance pore measured
      with a YO-PRO-1 uptake assay. Furthermore, P2Y6 activation modulates the ATP
      dependent migration of microglia, a process likely involved in their shift from
      migratory to phagocytic phenotype. Reconstituting the P2X4-P2Y6 interaction in
      recombinant systems shows that P2Y6 activation decreases P2X4 current amplitude,
      activation and desensitization rates, and reduces P2X4 channel permeability to
      the large cation NMDG(+) . Phospholipase C-mediated hydrolysis of the
      phosphoinositide PI(4,5)P2 , a necessary cofactor for P2X4 channel function,
      underlies this inhibitory crosstalk. As extracellular levels of both ATP and UDP
      are increased in the spinal cord following nerve injury, the control of P2X4
      activity by P2Y6 might play a critical role in regulating neuropathic pain
      inducing microglial responses.

PMID- 24123516
TI  - Probing helical hydrophobic binding sites in branched starch polysaccharides
      using NMR spectroscopy.
AB  - Branched starch polysaccharides are capable of binding multiple hydrophobic
      guests, but their exploitation as multivalent hosts and in functional materials
      is limited by their structural complexity and diversity. Linear alpha(1-4)-linked
      glucose oligosaccharides are known to bind hydrophobic guests inside left-handed
      single helices in solution and the solid state. Here, we describe the development
      of an amphiphilic probe that binds to linear alpha(1-4)-linked glucose
      oligosaccharides and undergoes a conformational switch upon complexation, which
      gives rise to dramatic changes in the (1)H NMR spectrum of the probe. We use this
      probe to explore hydrophobic binding sites in the branched starch polysaccharides
      amylopectin and beta-limit dextrin. Diffusion-ordered (DOSY), nuclear Overhauser
      effect (NOESY) and chemical shift perturbation (HSQC) NMR experiments are
      utilised to provide evidence that, in aqueous solution, branched polysaccharides
      bind hydrophobic guests in well-defined helical binding sites, similar to those
      reported for complexation by linear oligosaccharides. By examining the binding
      affinity of the probe to systematically enzymatically degraded polysaccharides,
      we deduce that the binding sites for hydrophobic guests can be located on
      internal as well as external branches and that proximal alpha(1-6)-linked branch
      points weaken but do not prevent complexation.

PMID- 24123517
TI  - Breast MRI at 7 Tesla with a bilateral coil and robust fat suppression.
AB  - PURPOSE: To develop a bilateral coil and fat suppressed T1-weighted sequence for
      7 Tesla (T) breast MRI. MATERIALS AND METHODS: A dual-solenoid coil and three
      dimensional (3D) T1w gradient echo sequence with B1+ insensitive fat suppression
      (FS) were developed. T1w FS image quality was characterized through image
      uniformity and fat-water contrast measurements in 11 subjects. Signal-to-noise
      ratio (SNR) and flip angle maps were acquired to assess the coil performance.
      Bilateral contrast-enhanced and unilateral high resolution (0.6 mm isotropic, 6.5
      min acquisition time) imaging highlighted the 7T SNR advantage. RESULTS: Reliable
      and effective FS and high image quality was observed in all subjects at 7T,
      indicating that the custom coil and pulse sequence were insensitive to high-field
      obstacles such as variable tissue loading. 7T and 3T image uniformity was similar
      (P=0.24), indicating adequate 7T B1+ uniformity. High 7T SNR and fat-water
      contrast enabled 0.6 mm isotropic imaging and visualization of a high level of
      fibroglandular tissue detail. CONCLUSION: 7T T1w FS bilateral breast imaging is
      feasible with a custom radiofrequency (RF) coil and pulse sequence. Similar image
      uniformity was achieved at 7T and 3T, despite different RF field behavior and
      variable coil-tissue interaction due to anatomic differences that might be
      expected to alter magnetic field patterns.

PMID- 24123518
TI  - Elastic network normal mode dynamics reveal the GPCR activation mechanism.
AB  - G-protein-coupled receptors (GPCR) are a family of membrane-embedded metabotropic
      receptors which translate extracellular ligand binding into an intracellular
      response. Here, we calculate the motion of several GPCR family members such as
      the M2 and M3 muscarinic acetylcholine receptors, the A2A adenosine receptor, the
      beta2 -adrenergic receptor, and the CXCR4 chemokine receptor using elastic
      network normal modes. The normal modes reveal a dilation and a contraction of the
      GPCR vestibule associated with ligand passage, and activation, respectively.
      Contraction of the vestibule on the extracellular side is correlated with cavity
      formation of the G-protein binding pocket on the intracellular side, which
      initiates intracellular signaling. Interestingly, the normal modes of rhodopsin
      do not correlate well with the motion of other GPCR family members. Electrostatic
      potential calculation of the GPCRs reveal a negatively charged field around the
      ligand binding site acting as a siphon to draw-in positively charged ligands on
      the membrane surface. Altogether, these results expose the GPCR activation
      mechanism and show how conformational changes on the cell surface side of the
      receptor are allosterically translated into structural changes on the inside.

PMID- 24123519
TI  - Evidence of subclinical prion disease in aged mice following exposure to bovine
      spongiform encephalopathy.
AB  - The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost
      certainly the result of consumption of food contaminated with bovine spongiform
      encephalopathy (BSE) prions. Despite probable widespread exposure of the UK
      population to BSE-contaminated food in the 1980s, vCJD has been identified
      predominantly in young individuals, and there have been fewer cases of clinical
      disease than anticipated. The reasons for this are uncertain. Following
      peripheral exposure, many prions replicate within the lymphoid tissues before
      infecting the central nervous system. We have shown that the effects of host age
      on the microarchitecture of the spleen significantly impair susceptibility to
      mouse-adapted prions after peripheral exposure. The transmission of prions
      between different mammalian species is considered to be limited by the 'species
      barrier', which is dependent on several factors, including an intact immune
      system. Thus, cross-species prion transmission may be much less efficient in aged
      individuals. To test this hypothesis, we compared prion pathogenesis in groups of
      young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE
      brain homogenate. We showed that prion pathogenesis was impaired dramatically in
      aged mice when compared with young animals. Whereas most young mice succumbed to
      clinical prion disease, all aged mice failed to develop clinical disease during
      their lifespans. However, the demonstration that prion accumulation was detected
      in the lymphoid tissues of some aged mice after injection with primary BSE brain
      homogenate, in the absence of clinical signs of prion disease, has important
      implications for human health. 

PMID- 24123521
TI  - Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and
      modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential.
AB  - Viruses modulate the functions of mitochondria by translocating viral proteins to
      the mitochondria. Subcellular fractionation and sensitivity to proteinase
      K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3
      infected/transfected cells suggested that core protein pVII localizes to the
      mitochondria and contains a functional mitochondrial localization signal.
      Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the
      retention of mitochondrial Ca(2+), inducing a significant increase in the levels
      of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected
      cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant
      effect on the levels of cytoplasmic Ca(2+) and reactive oxygen species production
      in the transfected cells. Consistent with these results, expression of pVII in
      transfected cells treated with staurosporine decreased significantly the
      activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to
      mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by
      increasing mitochondrial Ca(2+) and ATP production. 

PMID- 24123522
TI  - Body image disturbance and quality of life in Chinese patients with ankylosing
      spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a painful inflammatory disease of the
      axial skeleton that can cause body image disturbance (BID) and may lead to
      psychological changes in AS patients. OBJECTIVE: This study investigated the
      effect of AS patient physical and psychological status on BID and quality of life
      (QOL). METHODS: Overall, 112 AS patients (84 males, 28 females; mean age, 32.8 +/
      10.8) and 127 healthy age-matched individuals (control group; 78 males, 49
      females; mean age, 36.9 +/- 12.6) were screened for inclusion in the single
      centre study. Multiple instruments assessing physical function, psychological
      function, body image, and QOL were applied. Multivariate stepwise regression
      analyses were used to determine factors associated with BID, anxiety, and
      depression. RESULTS: Of 103 AS patients and 121 control subjects, AS patients
      exhibited greater BID-associated social function, social life, and role function
      impairments (BID Questionnaire [BIDQ] 2.42 vs. 1.02; 2.20 vs. 1.19; 2.54 vs.
      0.72, respectively), lower behavioural avoidance (BIDQ 3.07 vs. 3.49), and
      similar decreases in vitality and mental health (p < .01). Impaired social
      function predicted anxiety and depression in AS patients. Disease status (daily
      activity, general health, and pain) and psychological status (BID, anxiety, and
      depression) predicted poor QOL (p < .05). CONCLUSION: BID may play a significant
      role in causing clinical psychological dysfunction in AS patients, including
      anxiety and depression. Further research is required to fully assess whether
      these observations are similar in patients with variant AS severity. BID may be
      useful in clinical prognostic assessment and AS management. PRACTITIONER POINTS:
      AS patients investigated in this study exhibited BID. There were significant
      relationships between the BIDQ, disease and psychological variables, and QOL.
      Disease status, BID, and anxiety and depression indicated a poor QOL.

PMID- 24123523
TI  - Bell-shaped superhydrophilic-superhydrophobic-superhydrophilic double
      transformation on a pH-responsive smart surface.
AB  - Superhydrophobic to neutral water droplets, superhydrophilic to acidic or basic.
      This double transition of surface wettability in response to a single stimulus -
      pH - is demonstrated for the first time. The smart surface is composed of a rough
      gold surface modified with a self-assembled monolayer (SAM) containing three
      thiols, HS(CH2 )11 CH3 , HS(CH2 )10 COOH, and HS(CH2 )11 NH2 . A ternary diagram
      is generated that describes wettability as a function of the SAM composition and
      the pH of the surrounding solution.

PMID- 24123524
TI  - Missing small-bandgap metallofullerenes: their isolation and electronic
      properties.

PMID- 24123525
TI  - Rapamycin-sensitive mTORC1 signaling is involved in physiological primordial
      follicle activation in mouse ovary.
AB  - In mammals, resting female oocytes reside in primordial ovarian follicles. An
      individual primordial follicle may stay quiescent for a protracted period of time
      before initiating follicular growth, which is also termed "activation." Female
      reproductive capacity is sustained by the gradual, streamlined activation of the
      entire population of primordial follicles, but this process also results in
      reproductive senescence in older animals. Based on the recent findings that
      genetically triggered, excessive mammalian target of rapamycin complex 1 (mTORC1)
      activation in mouse oocytes leads to accelerated primordial follicle activation,
      we examined the necessity of mTORC1 signaling in physiological primordial
      follicle activation. We found that induction of oocyte mTORC1 activity is
      associated with early follicular growth in neonatal mouse ovaries.
      Pharmacological inhibition of mTORC1 activity in vivo by rapamycin treatment
      leads to a marked, but partial, suppression of primordial follicle activation.
      The suppressive effect of rapamycin on primordial follicle activation was
      reproduced in cultured ovaries. While rapamycin did not apparently affect several
      plausible cellular targets in neonatal mouse ovaries, such as mTORC2, AKT, or
      cyclin-dependent kinase (CDK) inhibitor p27-KIP1, its inhibitory effect on Cyclin
      A2 gene expression implies that mTORC1 signaling in oocytes may engage a Cyclin
      A/CDK regulatory network that promotes primordial follicle activation. The
      current work strengthens the concept that mTORC1-dependent events in the oocytes
      of primordial follicles may represent potential targets for intervention in
      humans to slow the depletion of the ovarian reserve.

PMID- 24123526
TI  - Early response as a predictor of success in guided self-help treatment for
      bulimic disorders.
AB  - The aims of this study were to investigate the number of sessions and time
      required for a clinical meaningful symptomatic change with a guided self-help
      treatment and to assess the predictive value of early response and other
      potential predictors of end-of-treatment clinical status. Participants were 42
      patients with a diagnosis of bulimia nervosa or ED not otherwise specified.
      Survival analyses (Kaplan-Meier) were performed to estimate the median time
      required to attain a 51% reduction in bulimic symptoms. Logistic regression was
      used to assess predictors of symptom remission. Results showed that the median
      time to achieve a 51% reduction in binge and purge frequencies was 3.68 and 3.77,
      respectively. This change occurred at session 3 for 50% of the participants.
      Early response was the most significant predictor of binge eating remission. No
      pretreatment predictors of time to achieve early response were found. These
      results have implications for allocating treatment resources in a stepped-care
      intervention model.

PMID- 24123527
TI  - Child-to-teacher ratio and day care teacher sickness absenteeism.
AB  - The literature on occupational health points to work pressure as a trigger of
      sickness absence. However, reliable, objective measures of work pressure are in
      short supply. This paper uses Danish day care teachers as an ideal case for
      analysing whether work pressure measured by the child-to-teacher ratio, that is,
      the number of children per teacher in an institution, affects teacher sickness
      absenteeism. We control for individual teacher characteristics, workplace
      characteristics, and family background characteristics of the children in the day
      care institutions. We perform estimations for two time periods, 2002-2003 and
      2005-2006, by using generalized method of moments with lagged levels of the child
      to-teacher ratio as instrument. Our estimation results are somewhat mixed.
      Generally, the results indicate that the child-to-teacher ratio is positively
      related to short-term sickness absence for nursery care teachers, but not for
      preschool teachers.

PMID- 24123529
TI  - Unveiling photodeactivation pathways for a new iridium(III) cyclometalated
      complex.
AB  - We report the synthesis and characterization of a neutral heteroleptic Ir(III)
      complex bearing 6-fluoro-2-phenylbenzo[d]thiazole as cyclometalating ligand and
      (Z)-6-(9H-carbazol-9-yl)-5-hydroxy-2,2-dimethylhex-4-en-3-one as ancillary
      ligand. The photodeactivation mechanisms have been elucidated through extensive
      density functional theory (DFT) calculations. The active role of metal-centered
      ((3) MC) triplet excited states in the nonradiative deactivation pathways is, for
      first time, confirmed in such complexes. 

PMID- 24123528
TI  - Method to create regional mechanical dyssynchrony maps from short-axis cine
      steady-state free-precession images.
AB  - PURPOSE: To develop a robust method to assess regional mechanical dyssynchrony
      from cine short-axis MR images. Cardiac resynchronization therapy (CRT) is an
      effective treatment for patients with heart failure and evidence of left
      ventricular (LV) dyssynchrony. Patient response to CRT is greatest when the LV
      pacing lead is placed in the most dyssynchronous segment. Existing techniques for
      assessing regional dyssynchrony require difficult acquisition and/or
      postprocessing. Our goal was to develop a widely applicable and robust method to
      assess regional mechanical dyssynchrony. MATERIALS AND METHODS: Using the
      endocardial boundary, radial displacement curves (RDCs) were generated throughout
      the LV. Cross-correlation was used to determine the delay time between each RDC
      and a patient-specific reference. Delay times were projected onto the American
      Heart Association 17-segment model creating a regional dyssynchrony map. Our
      method was tested in 10 normal individuals and 10 patients enrolled for CRT (QRS
      > 120 ms, NYHA III-IV, EF < 35%). RESULTS: Delay times over the LV were 23.9 +/-
      33.8 ms and 93.1 +/- 99.9 ms (P < 0.001) in normal subjects and patients,
      respectively. Interobserver reproducibility for segment averages was 6.8 +/- 39.3
      ms and there was 70% agreement in identifying the latest contracting segment.
      CONCLUSION: We have developed a method that can reliably calculate regional delay
      times from cine steady-state free-precession (SSFP) images. Maps of regional
      dyssynchrony could be used to identify the latest-contracting segment to assist
      in CRT lead implantation.

PMID- 24123530
TI  - Water-solid surface contact electrification and its use for harvesting liquid
      wave energy.

PMID- 24123532
TI  - Long-term dynamics of mycorrhizal root tips in a loblolly pine forest grown with
      free-air CO2 enrichment and soil N fertilization for 6 years.
AB  - Large-scale, long-term FACE (Free-Air CO2 enrichment) experiments indicate that
      increases in atmospheric CO2 concentrations will influence forest C cycling in
      unpredictable ways. It has been recently suggested that responses of mycorrhizal
      fungi could determine whether forest net primary productivity (NPP) is increased
      by elevated CO2 over long time periods and if forests soils will function as
      sources or sinks of C in the future. We studied the dynamic responses of
      ectomycorrhizae to N fertilization and atmospheric CO2 enrichment at the Duke
      FACE experiment using minirhizotrons over a 6 year period (2005-2010).
      Stimulation of mycorrhizal production by elevated CO2 was observed during only 1
      (2007) of 6 years. This increased the standing crop of mycorrhizal tips during
      2007 and 2008; during 2008, significantly higher mortality returned standing crop
      to ambient levels for the remainder of the experiment. It is therefore unlikely
      that increased production of mycorrhizal tips can explain the lack of progressive
      nitrogen limitations and associated increases in N uptake observed in CO2 
      enriched plots at this site. Fertilization generally decreased tree reliance on
      mycorrhizae as tip production declined with the addition of nitrogen as has been
      shown in many other studies. Annual NPP of mycorrhizal tips was greatest during
      years with warm January temperatures and during years with cool spring
      temperatures. A 2  degrees C increase in average late spring temperatures (May
      and June) decreased annual production of mycorrhizal root tip length by 50%. This
      has important implications for ecosystem function in a warmer world in addition
      to potential for forest soils to sequester atmospheric C. 

PMID- 24123531
TI  - HRAS mutations and resistance to the epidermal growth factor receptor tyrosine
      kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.
AB  - BACKGROUND: The purpose of this study was to identify mechanisms of innate
      resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC)
      cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib
      resistance. METHODS: Erlotinib sensitivity was determined by methyl thiazolyl
      tetrazolium (MTT) assays. Molecular signaling pathways and somatic mutations were
      examined. Changes in sensitivity after modulation of HRAS expression were
      evaluated. RESULTS: All 7 cell lines were wild-type for EGFR and KRAS regardless
      of erlotinib sensitivity; however, 1 erlotinib-resistant cell line (HN31)
      harbored an HRAS G12D mutation. Downregulation of HRAS expression by small
      interfering RNA (siRNA) or short hairpin RNA (shRNA) in HN31 led to increased
      erlotinib sensitivity in vitro and in vivo. Transfection of activating HRAS
      mutant (G12D and G12V) constructs into erlotinib-sensitive cell lines made them
      more resistant to erlotinib. CONCLUSION: Activating HRAS mutations can confer
      erlotinib resistance in an HRAS mutant HNSCC cell line.

PMID- 24123533
TI  - Integrated hollow mesoporous silica nanoparticles for target drug/siRNA co
      delivery.
AB  - A hollow mesoporous silica nanoparticle (HMSNP) based drug/siRNA co-delivery
      system was designed and fabricated, aiming at overcoming multidrug resistance
      (MDR) in cancer cells for targeted cancer therapy. The as-prepared HMSNPs have
      perpendicular nanochannels connecting to the internal hollow cores, thereby
      facilitating drug loading and release. The extra volume of the hollow core
      enhances the drug loading capacity by two folds as compared with conventional
      mesoporous silica nanoparticles (MSNPs). Folic acid conjugated polyethyleneimine
      (PEI-FA) was coated on the HMSNP surfaces under neutral conditions through
      electrostatic interactions between the partially charged amino groups of PEI-FA
      and the phosphate groups on the HMSNP surfaces, blocking the mesopores and
      preventing the loaded drugs from leakage. Folic acid acts as the targeting ligand
      that enables the co-delivery system to selectively bind with and enter into the
      target cancer cells. PEI-FA-coated HMSNPs show enhanced siRNA binding capability
      on account of electrostatic interactions between the amino groups of PEI-FA and
      siRNA, as compared with that of MSNPs. The electrostatic interactions provide the
      feasibility of pH-controlled release. In vitro pH-responsive drug/siRNA co
      delivery experiments were conducted on HeLa cell lines with high folic acid
      receptor expression and MCF-7 cell lines with low folic acid receptor expression
      for comparison, showing effective target delivery to the HeLa cells through folic
      acid receptor meditated cellular endocytosis. The pH-responsive intracellular
      drug/siRNA release greatly minimizes the prerelease and possible side effects of
      the delivery system. By simultaneously delivering both doxorubicin (Dox) and
      siRNA against the Bcl-2 protein into the HeLa cells, the expression of the anti
      apoptotic protein Bcl-2 was successfully suppressed, leading to an enhanced
      therapeutic efficacy. Thus, the present multifunctional nanoparticles show
      promising potentials for controlled and targeted drug and gene co-delivery in
      cancer treatment. 

PMID- 24123534
TI  - Size-dependent temperature sensitivity of photoluminescence peak position of CdTe
      quantum dots.
AB  - The size dependence of the temperature coefficient (sensitivity) of the
      photoluminescence (PL) peak position of CdTe quantum dots stabilized by
      thioglycolic acid in aqueous solution has been investigated. Temperature
      sensitivity increases as the average radius of CdTe quantum dots decreases. This
      must be taken into account in the design of solar light concentrators and light
      emmiting diode-monitors as well as other technologies in which a fine tuning of
      the light emission is important.

PMID- 24123535
TI  - Beta-band activity in auditory pathways reflects speech localization and
      recognition in bilateral cochlear implant users.
AB  - In normal-hearing listeners, localization of auditory speech involves stimulus
      processing in the postero-dorsal pathway of the auditory system. In quiet
      environments, bilateral cochlear implant (CI) users show high speech recognition
      performance, but localization of auditory speech is poor, especially when
      discriminating stimuli from the same hemifield. Whether this difficulty relates
      to the inability of the auditory system to translate binaural electrical cues
      into neural signals, or to a functional reorganization of auditory cortical
      pathways following long periods of binaural deprivation is unknown. In this
      electroencephalography study, we examined the processing of auditory syllables in
      postlingually deaf adults with bilateral CIs and in normal-hearing adults.
      Participants were instructed to either recognize ("recognition" task) or localize
      ("localization" task) the syllables. The analysis focused on event-related
      potentials and oscillatory brain responses. N1 amplitudes in CI users were larger
      in the localization compared with recognition task, suggesting an enhanced
      stimulus processing effort in the localization task. Linear beamforming of
      oscillatory activity in CI users revealed stronger suppression of beta-band
      activity after 200 ms in the postero-dorsal auditory pathway for the localization
      compared with the recognition task. In normal-hearing adults, effects for longer
      latency event-related potentials were found, but no effects were observed for N1
      amplitudes or beta-band responses. Our study suggests that difficulties in speech
      localization in bilateral CI users are not reflected in a functional
      reorganization of cortical auditory pathways. New signal processing strategies of
      cochlear devices preserving unambiguous binaural cues may improve auditory
      localization performance in bilateral CI users.

PMID- 24123536
TI  - Enantiodivergent deprotonation/acylation of alpha-amino nitriles.
AB  - Back to 'base'ics: The title reaction of enantioenriched alpha-ureidonitriles was
      found to proceed in a highly enantiodivergent manner despite the intermediacy of
      stereolabile alpha-nitrile metallocarbanions. Enantiodivergence is dependent upon
      the base used. For the less basic hexamethyldisilazides (HMDS), deprotonation in
      which a metal (M) cation is precomplexed with an electrophile is proposed.
      LDA=lithium diisopropylamide. 

PMID- 24123537
TI  - Connective tissue reaction of rats to a new zinc-oxide-eugenol endodontic sealer.
AB  - The aim of this study was to evaluate the biocompatibility in rat subcutaneous
      connective tissue of a new zinc oxide endodontic sealer (Endomethasone N)
      compared to those provided by Endofill and Sealer 26. Polyethylene tubes
      containing the test materials were implanted into dorsal subcutaneous connective
      tissue of Wistar albino rats. After 7 and 42 days, the implants with the
      surrounding tissue were collected, fixed, and processed for histologic
      evaluation. Sections were evaluated for the presence of inflammatory cells (poly
      or monomorfonuclear), blood vessels, necrosis area, and thickness of fibrous
      capsule. Comparisons between groups and time-periods were performed with Kruskal
      Wallis and Mann-Whitney U non-parametric tests for 5% significance level. No
      differences in the biocompatibility patterns among the materials for the 2
      experimental periods were observed. Independently of the sealer, the tissue
      behavior showed a tendency to decrease the irritation effect over time. It can be
      concluded that all sealers are irritant, but its toxicity decreased with time.
      Endomethasone N showed biocompatible characteristics comparable with those
      provided by Endofill and Sealer 26.

PMID- 24123538
TI  - The effects of Panax notoginseng saponins (PNS) on the activities of 'rat'
      CYP2C9, CYP2D6 and CYP3A4.

PMID- 24123539
TI  - Assessment of selection and resistance risk for demethylation inhibitor
      fungicides in Aspergillus fumigatus in agriculture and medicine: a critical
      review.
AB  - BACKGROUND: An increasing number of publications have claimed that demethylation
      inhibitor (DMI) fungicides are confronted with resistance development in the
      fungus Aspergillus fumigatus and that the origin of resistant isolates may also
      be outside the medical area. For resistance risk assessment and sourcing the
      origin of DMI resistance, the primary exposure events ofA. fumigatus with DMI
      treatments have been analysed case by case, resulting in the pathogen exposure
      risk (PER). RESULTS: The calculated maximum exposure concentrations (MEC) are
      highest during medical treatments (human and veterinary), certain fruit and seed
      treatments and wood preservation, and are much lower for crop protection
      applications. Most agricultural DMIs are intrinsically ~10-100 times less active
      than medical DMIs for A. fumigatus control and potential resistance selection.
      However, imazalil is used in agriculture and veterinary medicine (as
      enilconazole) expressing strong intrinsic activity against A. fumigatus. The
      majority of mutations in the target gene, cyp51, of DMI-resistant isolates are
      different in A. fumigatus(e.g. TR34/L98H) in comparison with plant pathogens
      (e.g. A379G, I381V). CONCLUSIONS: The assumed selection risk, ASR (MEC * PER) for
      resistance evolution to DMIs in A. fumigatus is estimated to be highest for human
      and veterinary applications. However, environmental origin of DMI-resistant
      spores from certain sites cannot be ruled out.

PMID- 24123540
TI  - Skeletal variability in the pelvis and limb skeleton of humans: does stabilizing
      selection limit female pelvic variation?
AB  - OBJECTIVES: This study tests the hypothesis, a correlate of the obstetric
      dilemma, that skeletal variability in the human female pelvic canal is limited
      owing to the action of stabilizing selection. Levels of variation in three
      skeletal regions (pelvic canal, noncanal pelvis, and limbs) of females and males
      are compared to each other and between sexes. METHODS: Nine human skeletal
      samples (total female n = 101; male n = 117) representing diverse populations
      were included. Osteometric data were collected from the articulated pelvis, os
      coxa, sacrum, femur, tibia, humerus, radius, and clavicle. Coefficients of
      variation, adjusted for small sample size (V*), were calculated for variables in
      separate samples by sex, and mean V*s were taken for the skeletal regions. Size
      variances were measured as V* of the geometric mean (GM) of the skeletal region
      variables. Using nonparametric methods, coefficients were compared between sexes
      and skeletal regions and correlations among V*s were calculated. RESULTS: Females
      and males do not differ in levels of variation for any skeletal region. The
      pelvic canal is the most variable region in both sexes, while size variability
      (GM) is similar among the three skeletal regions. Across the samples, canal and
      noncanal pelvic regions share patterns of variability in females but not males,
      while variability of the limb skeleton is independent in both sexes. CONCLUSIONS:
      The results suggest that stabilizing selection does not limit variability in the
      female pelvic canal. Biological plasticity may be greater in the canal than that
      in other skeletal regions.

PMID- 24123542
TI  - Automatic detection of arterial input function in dynamic contrast enhanced MRI
      based on affinity propagation clustering.
AB  - PURPOSE: To automatically and robustly detect the arterial input function (AIF)
      with high detection accuracy and low computational cost in dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: In this
      study, we developed an automatic AIF detection method using an accelerated
      version (Fast-AP) of affinity propagation (AP) clustering. The validity of this
      Fast-AP-based method was proved on two DCE-MRI datasets, i.e., rat kidney and
      human head and neck. The detailed AIF detection performance of this proposed
      method was assessed in comparison with other clustering-based methods, namely
      original AP and K-means, as well as the manual AIF detection method. RESULTS:
      Both the automatic AP- and Fast-AP-based methods achieved satisfactory AIF
      detection accuracy, but the computational cost of Fast-AP could be reduced by
      64.37-92.10% on rat dataset and 73.18-90.18% on human dataset compared with the
      cost of AP. The K-means yielded the lowest computational cost, but resulted in
      the lowest AIF detection accuracy. The experimental results demonstrated that
      both the AP- and Fast-AP-based methods were insensitive to the initialization of
      cluster centers, and had superior robustness compared with K-means method.
      CONCLUSION: The Fast-AP-based method enables automatic AIF detection with high
      accuracy and efficiency.

PMID- 24123541
TI  - Primary amenorrhea in anorexia nervosa: impact on characteristic masculine and
      feminine traits.
AB  - Animal studies indicate that gonadal hormones at puberty have an effect on the
      development of masculine and feminine traits. However, it is unknown whether
      similar processes occur in humans. We examined whether women with anorexia
      nervosa (AN), who often experience primary amenorrhea, exhibit attenuated
      feminization in their psychological characteristics in adulthood due to the
      decrease/absence of gonadal hormones at puberty. Women with AN were compared on a
      number of psychological characteristics using general linear models on the basis
      of the presence/absence of primary amenorrhea. Although women with primary
      amenorrhea exhibited lower anxiety scores than those without primary amenorrhea,
      in general, results did not provide evidence of attenuated feminization in women
      with AN with primary amenorrhea. Future research should utilize novel techniques
      and direct hormone measurement to explore the effects of pubertal gonadal
      hormones on masculine and feminine traits.

PMID- 24123543
TI  - Conformational selection of ubiquitin quaternary structures driven by zinc ions.
AB  - Zinc ions bridging two ubiquitin molecules (with His68 at the interface)
      contribute to select a subset of conformers from the noncovalent dimer ensemble,
      thus restricting quaternary structure dynamics, which hampers apo-protein
      crystallization. The type of selected conformer is shown to determine the crystal
      packing, which varies from orthorhombic to cubic symmetry. 

PMID- 24123544
TI  - Controlled thermolysis of uranium (alkoxy)siloxy complexes: a route to
      polymetallic complexes of low-valent uranium.

PMID- 24123545
TI  - Robust estimation of pulse wave transit time using group delay.
AB  - PURPOSE: To evaluate the efficiency of a novel transit time (Deltat) estimation
      method from cardiovascular magnetic resonance flow curves. MATERIALS AND METHODS:
      Flow curves were estimated from phase contrast images of 30 patients. Our method
      (TT-GD: transit time group delay) operates in the frequency domain and models the
      ascending aortic waveform as an input passing through a discrete-component
      "filter," producing the observed descending aortic waveform. The GD of the filter
      represents the average time delay (Deltat) across individual frequency bands of
      the input. This method was compared with two previously described time-domain
      methods: TT-point using the half-maximum of the curves and TT-wave using cross
      correlation. High temporal resolution flow images were studied at multiple
      downsampling rates to study the impact of differences in temporal resolution.
      RESULTS: Mean Deltats obtained with the three methods were comparable. The TT-GD
      method was the most robust to reduced temporal resolution. While the TT-GD and
      the TT-wave produced comparable results for velocity and flow waveforms, the TT
      point resulted in significant shorter Deltats when calculated from velocity
      waveforms (difference: 1.8+/-2.7 msec; coefficient of variability: 8.7%). The TT
      GD method was the most reproducible, with an intraobserver variability of 3.4%
      and an interobserver variability of 3.7%. CONCLUSION: Compared to the traditional
      TT-point and TT-wave methods, the TT-GD approach was more robust to the choice of
      temporal resolution, waveform type, and observer.

PMID- 24123547
TI  - Fabrication of all-carbon nanotube electronic devices on flexible substrates
      through CVD and transfer methods.
AB  - SWNT thin films with different nanotube densities are fabricated by CVD while
      controlling the concentration of catalyst and growth time. Three layers of SWNT
      films are transferred to flexible substrates serving as electrodes and channel
      materials, respectively. All-carbon nanotube TFTs with an on/off ratio as high as
      10(5) are obtained. Inverters are fabricated on top of the flexible substrates
      with symmetric input/output behavior. 

PMID- 24123546
TI  - Theoretical modelling of photoswitching of hyperpolarisabilities in ruthenium
      complexes.
AB  - Static excited-state polarisabilities and hyperpolarisabilities of three Ru(II)
      ammine complexes are computed at the density functional theory (DFT) and several
      correlated ab initio levels. Most accurate modelling of the low energy electronic
      absorption spectrum is obtained with the hybrid functionals B3LYP, B3P86 or M06
      for the complex [Ru(II)(NH3)5(MeQ(+))](3+) (MeQ(+)=N-methyl-4,4'-bipyridinium, 3)
      in acetonitrile. The match with experimental data is less good for
      [Ru(II)(NH3)5L](3+) (L=N-methylpyrazinium, 2; N-methyl-4-{E,E-4-(4-pyridyl)buta
      1,3-dienyl}pyridinium, 4). These calculations confirm that the first dipole-
      allowed excited state (FDAES) has metal-to-ligand charge-transfer (MLCT)
      character. Both the solution and gas-phase results obtained for 3 by using B3LYP,
      B3P86 or M06 are very similar to those from restricted active-space SCF second
      order perturbation theory (RASPT2) with a very large basis set and large active
      space. However, the time-dependent DFT lambda(max) predictions from the long
      range corrected functionals CAM-B3LYP, LC-omegaPBE and wB97XB and also the fully
      ab initio resolution of identity approximate coupled-cluster method (gas-phase
      only) are less accurate for all three complexes. The ground state (GS) two-state
      approximation first hyperpolarisability beta(2SA) for 3 from RASPT2 is very close
      to that derived experimentally via hyper-Rayleigh scattering, whereas the
      corresponding DFT-based values are considerably larger. The beta responses
      calculated by using B3LYP, B3P86 or M06 increase markedly as the pi-conjugation
      extends on moving along the series 2->4, for both the GS and FDAES species. All
      three functionals predict substantial FDAES beta enhancements for each complex,
      increasing with the pi-conjugation, up to about sevenfold for 4. Also, the
      computed second hyperpolarisabilities gamma generally increase in the FDAES, but
      the results vary between the different functionals.

PMID- 24123548
TI  - A new perspective on family involvement in chronic pain management programmes.
AB  - OBJECTIVES: The aim of this study was to investigate how those with pain, and
      their significant others, perceive the involvement of significant others in a
      multidisciplinary chronic pain management programme. METHODS: Semi-structured
      telephone interviews were conducted with eight people who had attended a Family
      Day as part of a three-week multidisciplinary chronic pain management programme
      in Auckland, New Zealand. Four of the participants had pain and four were
      significant others. Follow-up interviews were conducted with seven of the
      participants up to one year after their initial interview. Conventional content
      analysis was used to analyse collected data. RESULTS: Participants viewed the
      involvement of significant others to be important because managing pain
      necessitates 'being on the same page' and significant others also needed an
      opportunity to access support and information. CONCLUSION: The involvement of
      significant others in programmes is perceived to be important but must be a
      balance between what is feasible for significant others and beneficial for all.
      Further research into when and how significant others are included within
      programmes is urgently required.

PMID- 24123549
TI  - Cycloisomerization of 2-alkynylanilines to indoles catalyzed by carbon-supported
      gold nanoparticles and subsequent homocoupling to 3,3'-biindoles.

PMID- 24123550
TI  - Allosteric indicator displacement enzyme assay for a cyanogenic glycoside.
AB  - Indicator displacement assays (IDAs) represent an elegant approach in
      supramolecular analytical chemistry. Herein, we report a chemical biosensor for
      the selective detection of the cyanogenic glycoside amygdalin in aqueous
      solution. The hybrid sensor consists of the enzyme beta-glucosidase and a boronic
      acid appended viologen together with a fluorescent reporter dye. beta-Glucosidase
      degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and
      benzaldehyde. Only the released cyanide binds at the allosteric site of the
      receptor (boronic acid) thereby inducing changes in the affinity of a formerly
      bound fluorescent indicator dye at the other side of the receptor. Thus, the
      sensing probe performs as allosteric indicator displacement assay (AIDA) for
      cyanide in water. Interference studies with inorganic anions and glucose revealed
      that cyanide is solely responsible for the change in the fluorescent signal. DFT
      calculations on a model compound revealed a 1:1 binding ratio of the boronic acid
      and cyanide ion. The fluorescent enzyme assay for beta-glucosidase uses amygdalin
      as natural substrate and allows measuring Michaelis-Menten kinetics in microtiter
      plates. The allosteric indicator displacement assay (AIDA) probe can also be used
      to detect cyanide traces in commercial amygdalin samples. 

PMID- 24123551
TI  - Joined at the hip? A paleoepidemiological study of developmental dysplasia of the
      hip and its relation to swaddling practices among indigenous peoples of North
      America.
AB  - OBJECTIVES: Clinical prevalence of developmental dysplasia of the hip (DDH) is
      the highest among modern indigenous populations of North America, yet no
      systematic study of the paleoepidemiology of this group exists. This study
      discusses the skeletal criteria, epidemiology, pathophysiology, and risk factors
      for DDH. A range of cases of DDH from an archaeological Native American
      population are described, and the clinical and prehistoric prevalence of DDH
      among indigenous populations of North America are calculated and discussed within
      a biocultural perspective. METHODS: Pelves of 390 adults from the Late
      Prehistoric (1490 BP +/- 70) Buffalo site, West Virginia were examined for DDH.
      Morphology of true and false acetabula was classified and other changes of the
      pelvis, lower limb, and spine were noted along with cranial deformation,
      providing evidence of infant restriction. Prevalence of DDH among living and
      archaeological indigenous peoples of North America were calculated and compared.
      RESULTS: DDH was identified in eighteen adults from Buffalo, resulting in a
      prevalence of 46.15, within the range reported in modern indigenous groups in
      North America. However, there is a significant difference between the DDH
      prevalence in prehistory and today in the target population. CONCLUSIONS:
      Indigenous peoples of North America have the highest reported global prevalence
      of DDH today and in prehistory. The etiology of DDH suggests that components of
      both genetic predisposition and swaddling practices have combined to create a
      high-risk environment for the development of DDH, contributing to its high
      prevalence within archaeological populations, like Buffalo, and modern Native
      American/Aboriginal groups within North America.

PMID- 24123552
TI  - TPF induction chemotherapy and concomitant irradiation with cisplatin and
      cetuximab in unresectable squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of
      docetaxel, cisplatin/5-fluorouracil (TPF) induction chemotherapy and concomitant
      immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and
      neck carcinoma. METHODS: Treatment consisted of TPF induction chemotherapy
      (docetaxel 75 mg/m(2) day 2; cisplatin, 75 mg/m(2) day 2; and 5-fluorouracil 750
      mg/m(2) days 1-4; 4 cycles), followed by radiotherapy (RT) and concomitant weekly
      cetuximab, (250 mg/m(2), after a loading dose of 400 mg/m(2)) and cisplatin (30
      mg/m(2)). RESULTS: Twenty-five of 30 patients completed 4 cycles of induction
      chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were
      administered in 13 of 25 and 18 of 25 patients, respectively. The 2-year
      locoregional control, disease-free survival (DFS), and overall survival (OS) were
      47%, 47%, and 50%, respectively. Patients with grade >= 2 skin reaction to
      cetuximab had a superior outcome. CONCLUSION: The tested regimen was effective;
      however, cetuximab and low-dose cisplatin after induction TPF increased the
      treatment toxicity. A grade >= 2 skin rash correlated with improved efficacy.

PMID- 24123553
TI  - Functional neuroimaging of motor control in Parkinson's disease: a meta-analysis.
AB  - Functional neuroimaging has been widely used to study the activation patterns of
      the motor network in patients with Parkinson's disease (PD), but these studies
      have yielded conflicting results. This meta-analysis of previous neuroimaging
      studies was performed to identify patterns of abnormal movement-related
      activation in PD that were consistent across studies. We applied activation
      likelihood estimation (ALE) of functional neuroimaging studies probing motor
      function in patients with PD. The meta-analysis encompassed data from 283
      patients with PD reported in 24 functional neuroimaging studies and yielded
      consistent alterations in neural activity in patients with PD. Differences in
      cortical activation between PD patients and healthy controls converged in a left
      lateralized fronto-parietal network comprising the presupplementary motor area,
      primary motor cortex, inferior parietal cortex, and superior parietal lobule.
      Both, increases as well as decreases in motor cortical activity, which were
      related to differences in movement timing and selection in the applied motor
      tasks, were reported in these cortical areas. In the basal ganglia, PD patients
      expressed a decrease of motor activation in the posterior motor putamen, which
      improved with dopaminergic medication. The likelihood of detecting a decrease in
      putaminal activity increased with motor impairment. This reduced motor activation
      of the posterior putamen across previous neuroimaging studies indicates that
      nigrostriatal dopaminergic denervation affects neural processing in the
      denervated striatal motor territory. In contrast, fronto-parietal motor areas
      display both increases as well as decreases in movement related activation. This
      points to a more complex relationship between altered cortical physiology and
      nigrostriatal dopaminergic denervation in PD.

PMID- 24123554
TI  - Self-perceived job insecurity and the demand for medical rehabilitation: does
      fear of unemployment reduce health care utilization?
AB  - An inverse relationship between job insecurity and sickness absence has been
      established in the literature, which is explained by employees avoiding to send
      signals of both poor health and uncooperative behavior towards the employer. In
      this paper, we focus on whether the same mechanism applies to the demand for
      medical rehabilitation measures. This question has recently gained much interest
      in the context of the current public debate on presenteeism. Using county-level
      unemployment rates as instrument for the employees' fear of job loss on the
      individual level, we find that an increase in subjective job insecurity
      substantially decreases the probability of participating in medical
      rehabilitation.

PMID- 24123555
TI  - Hippocampal amnesia disrupts creative thinking.
AB  - Creativity requires the rapid combination and recombination of existing mental
      representations to create novel ideas and ways of thinking. The hippocampal
      system, through its interaction with neocortical storage sites, provides a
      relational database necessary for the creation, updating, maintenance, and
      juxtaposition of mental representations used in service of declarative memory.
      Given this functionality, we hypothesized that hippocampus would play a critical
      role in creative thinking. We examined creative thinking, as measured by verbal
      and figural forms of the torrance tests of creative thinking (TTCT), in a group
      of participants with hippocampal damage and severe declarative memory impairment
      as well as in a group of demographically matched healthy comparison participants.
      The patients with bilateral hippocampal damage performed significantly worse than
      comparison participants on both the verbal and figural portions of the TTCT.
      These findings suggest that hippocampus plays a role critical in creative
      thinking, adding to a growing body of work pointing to the diverse ways the
      hallmark processing features of hippocampus serve a variety of behaviors that
      require flexible cognition.

PMID- 24123556
TI  - The effect of black seed (Nigella sativa) extract on FOXO3 expression in HepG2
      cells.
AB  - Black seed extracts are known to alter cellular metabolism through multiple
      signaling pathways. Since Forkhead box transcription factor 3 (FOXO3) has a
      significant role in regulating cellular metabolism, the effect of lipid extracts
      of black seed (Sativa nigella) on FOXO3 levels and AKT and 5-AMP activated
      protein kinase alpha (AMPKalpha) signaling was measured in HepG2 hepatoma cells.
      FOXO3 levels, phosphorylation, and nuclear exclusion were measured by Western
      blot, as were AKT and AMPK expression and activity using phosphorylation-specific
      antibodies. Apolipoprotein A-I expression, a black seed-responsive gene, was
      measured by Western blot. Treatment with black seed extract increased FOXO3
      phosphorylation and decreased its expression. In contrast to control cells where
      FOXO3 was located primarily in the nucleus, in black seed-treated HepG2 cells,
      FOXO3 was localized primarily to the cytoplasm. These changes in FOXO3
      phosphorylation, expression, and localization were accompanied by increased AKT
      activity. Black seed also decreased AMPKalpha activity but increased AMPKalpha
      expression. Lipid extracts from black seeds inhibit FOXO3 activity and thereby
      modulate the expression of FOXO3-dependent genes.

PMID- 24123557
TI  - Dietary guild composition and disaggregation of avian assemblages under climate
      change.
AB  - Climate change is expected to cause geographic redistributions of species. To the
      extent that species within assemblages have different niche requirements,
      assemblages may no longer remain intact and dis- and reassemble at current or new
      geographic locations. We explored how climate change projected by 2100 may
      transform the world's avian assemblages (characterized at a 110 km spatial grain)
      by modeling environmental niche-based changes to their dietary guild structure
      under 0, 500, and 2000 km-dispersal distances. We examined guild structure
      changes at coarse (primary, high-level, and mixed consumers) and fine
      (frugivores, nectarivores, insectivores, herbivores, granivores, scavengers,
      omnivores, and carnivores) ecological resolutions to determine whether or not
      geographic co-occurrence patterns among guilds were associated with the magnitude
      to which guilds are functionally resolved. Dietary guilds vary considerably in
      their global geographic prevalence, and under broad-scale niche-based
      redistribution of species, these are projected to change very heterogeneously. A
      nondispersal assumption results in the smallest projected changes to guild
      assemblages, but with significant losses for some regions and guilds, such as
      South American insectivores. Longer dispersal distances are projected to cause
      greater degrees of disassembly, and lead to greater homogenization of guild
      composition, especially in northern Asia and Africa. This arises because
      projected range gains and losses result in geographically heterogeneous patterns
      of guild compensation. Projected decreases especially of primary and mixed
      consumers most often are compensated by increases in high-level consumers, with
      increasing uncertainty about these outcomes as dispersal distance and degree of
      guild functional resolution increase. Further exploration into the consequences
      of these significant broad-scale ecological functional changes at the community
      or ecosystem level should be increasingly on the agenda for conservation science.

PMID- 24123558
TI  - Selective reduction of barbituric acids using SmI2/H2O: synthesis, reactivity,
      and structural analysis of tetrahedral adducts.

PMID- 24123559
TI  - Attribution of somatic symptoms in hypochondriasis.
AB  - The misinterpretation of bodily symptoms as an indicator of a serious illness is
      a key feature of the criteria and the cognitive-behavioural models of
      hypochondriasis. Previous research suggests that individuals suffering from
      health anxiety endorse attributions of physical disease, whereas persons with
      elevated general anxiety have the tendency to attribute psychological causes to
      their symptoms. However, whether a somatic attribution style is specific to
      patients with hypochondriasis, as opposed to those with anxiety disorders, has
      not yet been investigated and is therefore part of the present study. Fifty
      patients with hypochondriasis, 50 patients with a primary anxiety disorder and 50
      healthy participants were presented with nine common bodily sensations and had to
      spontaneously attribute possible causes to the symptoms. Patients with
      hypochondriasis differed from patients with anxiety disorders and healthy
      controls in giving significantly fewer normalizing explanations, but attributing
      more often in terms of moderate or serious diseases. Patients with anxiety
      disorders also made significantly fewer normalizing attributions and more somatic
      attributions to a severe illness than healthy controls. There were no differences
      between the groups in the frequency of psychological attributions and somatic
      attributions concerning mild diseases. The present study demonstrates that
      hypochondriasis is associated with a disorder-specific attribution style
      connecting somatic symptoms primarily with moderate and serious diseases. By
      contrast, normalizing attributions are largely omitted from consideration by
      patients with hypochondriasis. The findings conform with the cognitive conception
      of hypochondriasis and support the strategy of modifying symptom attributions, as
      practiced in cognitive-behavioural therapy.

PMID- 24123560
TI  - A sustainable route towards imidazolium building blocks based on biomass
      molecules.

PMID- 24123561
TI  - A Uchl1-Histone2BmCherry:GFP-gpi BAC transgene for imaging neuronal progenitors.
AB  - Uchl1 encodes the protein gene product 9.5 antigen (PGP9.5) that is a widely used
      to identify migrating neural progenitors in the PNS, mature neurons of the
      central and peripheral nervous systems, as well as neuroendocrine cells. To
      facilitate analysis of developing peripheral neurons, we linked regulatory
      regions of Uchl1 carried within a 160kb bacterial artificial chromosome (BAC) to
      the dual fluorescent reporter H2BmCherry:GFP-gpi. The Uchl1-H2BmCherry:GFP-gpi
      transgene exhibits robust expression and allows clear discrimination of
      individual cells and cellular processes in cranial ganglia, sympathetic chain,
      the enteric nervous system (ENS), and autonomic ganglia of the urogenital system.
      The transgene also labels subsets of cells in endocrine tissues where earlier in
      situ hybridization (ISH) studies have previously identified expression of this
      deubiquinating enzyme. The Uchl1-H2BmCherry:GFP-gpi transgene will be a powerful
      tool for static and live imaging, as well as isolation of viable neural
      progenitors to investigate processes of autonomic neurogenesis.

PMID- 24123562
TI  - Comparison of treadmill exercise stress cardiac MRI to stress echocardiography in
      healthy volunteers for adequacy of left ventricular endocardial wall
      visualization: A pilot study.
AB  - PURPOSE: To compare exercise stress cardiac magnetic resonance (cardiac MR) to
      echocardiography in healthy volunteers with respect to adequacy of endocardial
      visualization and confidence of stress study interpretation. MATERIALS AND
      METHODS: Twenty-eight healthy volunteers (age 28 +/- 11 years, 15 males)
      underwent exercise stress echo and cardiac MR one week apart assigned randomly to
      one test first. Stress cardiac MR was performed using an MRI-compatible
      treadmill; stress echo was performed as per routine protocol. Cardiac MR and echo
      images were independently reviewed and scored for adequacy of endocardial
      visualization and confidence in interpretation of the stress study. RESULTS:
      Heart rate at the time of imaging was similar between the studies. Average time
      from cessation of exercise to start of imaging (21 vs. 31 s, P < 0.001) and time
      to acquire stress images (20 vs. 51 s, P < 0.001) was shorter for cardiac MR. The
      number of myocardial segments adequately visualized was significantly higher by
      cardiac MR at rest (99.8% vs. 96.4%, P = 0.002) and stress (99.8% vs. 94.1%, P =
      0.001). The proportion of subjects in whom there was high confidence in the
      interpretation was higher for cardiac MR than echo (96% vs. 60%, P = 0.005).
      CONCLUSION: Exercise stress cardiac MR to assess peak exercise wall motion is
      feasible and can be performed at least as rapidly as stress echo.

PMID- 24123563
TI  - Increases in weight during chronic stress are partially associated with a switch
      in food choice towards increased carbohydrate and saturated fat intake.
AB  - We examined if stress associated changes in weight and dietary restraint are
      associated with changes in the composition of foods consumed. Participants were
      38 healthy women on a taught postgraduate university course. Data were obtained
      at the beginning of the semester and 15 weeks later just prior to a written
      course exam (the stressor). By using a within subject design, we measured the
      composition of food consumed, body mass index (BMI), levels of dietary restraint
      and salivary cortisol. In the larger study from which these data were obtained,
      it was shown that the effect of increased cortisol secretion on weight gain was
      mediated by a reduction in dietary restraint. The present data show that
      increased cortisol secretion, reduced dietary restraint and increased caloric
      intake, account for 73% of the variance in change in BMI. Further regression
      analysis indicated that the change in dietary restraint mediated the effect of
      change in cortisol on change in BMI. Final analysis revealed that the effect of
      these changes in dietary restraint on weight are partially mediated by increased
      caloric intake from carbohydrate and saturated fat, that is, a change in dietary
      composition partially accounts for the link between increased cortisol secretion
      through heightened hypothalamic-pituitary-adrenal activity resulting in weight
      gain. These data are consistent with a 'comfort food hypothesis', as they suggest
      that chronic stress can promote reward associated behaviour through reduced
      dietary restraint and consumption of food containing more carbohydrate and
      saturated fat.

PMID- 24123564
TI  - Spin-crossover complex on Au(111): structural and electronic differences between
      mono- and multilayers.
AB  - Submono-, mono- and multilayers of the Fe(II) spin-crossover (SCO) complex
      [Fe(bpz)2 (phen)] (bpz=dihydrobis(pyrazolyl)borate, phen=1,10-phenanthroline)
      have beenprepared by vacuum deposition on Au(111) substrates and investigated
      with near edge X-ray absorption fine structure (NEXAFS) spectroscopy and scanning
      tunneling microscopy (STM). As evidenced by NEXAFS, molecules of the second layer
      exhibit a thermal spin crossover transition, although with a more gradual
      characteristics than in the bulk. For mono- and submonolayers of [Fe(bpz)2
      (phen)] deposited on Au(111) substrates at room temperature both NEXAFS and STM
      indicate a dissociation of [Fe(bpz)2 (phen)] on Au(111) into four-coordinate
      complexes, [Fe(bpz)2 ], and phen molecules. Keeping the gold substrate at
      elevated temperatures ordered monolayers of intact molecules of [Fe(bpz)2 (phen)]
      are formed which can be spin-switched by electron-induced excited spin-state
      trapping (ELIESST). 

PMID- 24123566
TI  - A novel multidisciplinary approach toward a better understanding of cranial
      suture closure: the first evidence of genetic effects in adulthood.
AB  - OBJECTIVES: The primary objective of this study was to perform new, relevant
      information about cranial suture closure in adults. Single nucleotide
      polymorphisms (SNPs) in targeted genes were examined, which encode factors that
      play an important role in cranial suture development and maintenance. Our
      hypothesis was that some of these genes and polymorphisms can influence the
      cranial suture obliteration status in adulthood as well. METHODS: Ossification of
      cranial sutures was ascertained according to Meindl and Lovejoy's vault system
      (1985: Am J Phys Anthropol 68(1):57-66), and peripheral blood samples were
      collected during autopsy procedure of 106 individuals at the Department of
      Forensic and Insurance Medicine, Semmelweis University, Hungary. Genotyping of
      SNPs was conducted using competitive allele-specific polymerase chain reaction
      KASPar chemistry. Multivariate linear models were used to test whether SNP
      polymorphism of the investigated genes has a significant effect on the
      ectocranial suture synostosis in adults. RESULTS: The msh homeobox 1 (MSX1):
      rs3821947 polymorphism showed significant association with the extent of suture
      obliteration. CONCLUSIONS: Cranial suture closure in adults is a complex,
      multifactorial process. According to previous results MSX1 has a role in
      calvarial bone development and it has an effect on sutural mesenchyme in latter
      postnatal stages. Our results demonstrate MSX1 effects on suture obliteration in
      adulthood. These findings represent new, relevant information indicating that
      genetic background can have an impact on cranial suture closure in adults.

PMID- 24123565
TI  - HIF1alpha modulates cell fate reprogramming through early glycolytic shift and
      upregulation of PDK1-3 and PKM2.
AB  - Reprogramming somatic cells to a pluripotent state drastically reconfigures the
      cellular anabolic requirements, thus potentially inducing cancer-like metabolic
      transformation. Accordingly, we and others previously showed that somatic
      mitochondria and bioenergetics are extensively remodeled upon derivation of
      induced pluripotent stem cells (iPSCs), as the cells transit from oxidative to
      glycolytic metabolism. In the attempt to identify possible regulatory mechanisms
      underlying this metabolic restructuring, we investigated the contributing role of
      hypoxia-inducible factor one alpha (HIF1alpha), a master regulator of energy
      metabolism, in the induction and maintenance of pluripotency. We discovered that
      the ablation of HIF1alpha function in dermal fibroblasts dramatically hampers
      reprogramming efficiency, while small molecule-based activation of HIF1alpha
      significantly improves cell fate conversion. Transcriptional and bioenergetic
      analysis during reprogramming initiation indicated that the transduction of the
      four factors is sufficient to upregulate the HIF1alpha target pyruvate
      dehydrogenase kinase (PDK) one and set in motion the glycolytic shift. However,
      additional HIF1alpha activation appears critical in the early upregulation of
      other HIF1alpha-associated metabolic regulators, including PDK3 and pyruvate
      kinase (PK) isoform M2 (PKM2), resulting in increased glycolysis and enhanced
      reprogramming. Accordingly, elevated levels of PDK1, PDK3, and PKM2 and reduced
      PK activity could be observed in iPSCs and human embryonic stem cells in the
      undifferentiated state. Overall, the findings suggest that the early induction of
      HIF1alpha targets may be instrumental in iPSC derivation via the activation of a
      glycolytic program. These findings implicate the HIF1alpha pathway as an enabling
      regulator of cellular reprogramming.

PMID- 24123567
TI  - Clinical significance of intraparotid lymph node metastasis in primary parotid
      cancer.
AB  - BACKGROUND: The clinical utility of intraparotid lymph node metastasis in primary
      parotid cancer is unknown, and this study was undertaken to address this gap in
      knowledge. METHODS: A medical chart review was performed on 86 patients who
      underwent parotidectomy with neck dissection (39 cN+ and 47 cN0). The disease
      specific mortality and locoregional recurrence (LRR) were correlated with
      intraparotid lymph node metastasis status. RESULTS: Using intraparotid lymph node
      metastasis status to predict cervical nodal metastasis resulted in a sensitivity
      and specificity of 70% and 90.6%, respectively (positive predictive value [PPV]
      of 87.3%). Patients with positive intraparotid lymph node metastasis had a worse
      3-year disease-specific mortality compared with patients with negative
      intraparotid lymph node metastasis (p = .0037). Patients with cN0 neck but
      positive intraparotid lymph node metastasis were more likely to develop
      locoregional recurrence than patients without intraparotid lymph node metastasis
      (p = .08). CONCLUSION: In patients with cN0 neck but positive intraparotid lymph
      node metastasis, intraparotid lymph node metastasis presence was strongly
      associated with a worse disease-specific survival and placed them at a higher
      risk of locoregional recurrence.

PMID- 24123568
TI  - Heterogeneity in action: the role of passive personalization in comparative
      effectiveness research.
AB  - Despite the goal of comparative effectiveness research (CER) to inform patient
      centered care, most studies fail to account for the patient-centeredness of care
      that already exist in practice, which we denote as passive personalization (PP).
      Because CER studies describe the average effectiveness of treatments rather than
      heterogeneity in how individual patients respond to therapies, clinical or
      coverage policies that respond to CER results may undermine PP in clinical
      practice and generate worse outcomes. We study this phenomenon empirically in the
      context of use of antipsychotic drugs in Medicaid patients with schizophrenia
      using novel instrumental variable methods. We find strong support for PP in
      clinical practice and demonstrate that the average effects from a CER study
      cannot be replicated in practice because of the presence of PP. In contrast,
      providing physicians with evidence to further personalize treatment can produce
      significant benefits.

PMID- 24123569
TI  - Place-related neuronal activity in the monkey parahippocampal gyrus and
      hippocampal formation during virtual navigation.
AB  - Neuropsychological data in primates demonstrated a pivotal role of the
      hippocampal formation (HF) and parahippocampal gyrus (PH) in navigation and
      episodic memory. To investigate the role of HF and PH neurons in environmental
      scaling in primates, we recorded neuronal activities in the monkey HF and PH
      during virtual navigation (VN) and pointer translocation (PT) tasks. The monkeys
      had to navigate within three differently sized virtual spaces with the same
      spatial cues (VN task) or move a pointer on a screen (PT task) by manipulating a
      joystick to receive a reward. Of the 234 recorded neurons, 170 and 61 neurons
      displayed place-related activities in the VN and PT tasks, respectively.
      Significant differences were observed between the HF and PH neurons. The spatial
      similarity of place fields between the two different virtual spaces was lower in
      PH than in HF, while specificities of the neuronal responses to distal spatial
      cues were higher in PH than in HF. Spatial view information was predominately
      processed in posterior PH. The spatial scales (place field sizes) of the HF and
      PH neurons were reduced in the reduced virtual space, as shown in rodent place
      cells. These results suggest the complementary roles of HF (allocentric
      representation of landmarks) and PH (representation of the spatial layout of
      landmarks) in the recognition of a location during navigation.

PMID- 24123570
TI  - Repetitive exposure of mice to strong static magnetic fields in utero does not
      impair fertility in adulthood but may affect placental weight of offspring.
AB  - PURPOSE: To investigate the effect of daily exposure in utero to static magnetic
      fields during prenatal development on germ cell development and fertility of
      exposed offspring in adulthood. MATERIALS AND METHODS: Mice were exposed daily in
      utero to different static magnetic field strengths at the bore entrance or in the
      isocenter of 1.5 T and 7 T MRI systems during the entire course of prenatal
      development. RESULTS: In utero-exposed male mice revealed no effect of magnetic
      field strength on weight of testes and epididymis or on sperm count, sperm
      morphology, or fertility. Exposed pregnant female mice showed no reduced
      fertility in terms of pregnancy rates and litter size, pointing to a normal
      ovarian function. However, a reduced placental weight of offspring of
      intrauterine exposed female mice was observed that correlated with a decrease in
      embryonic weight in those animals exposed at the strongest magnetic field. This
      effect seemed to be parent-dependent, since it was not observed in those embryos
      fathered by in utero-exposed male mice. CONCLUSION: Repetitive in utero exposure
      to strong static magnetic fields does not impair fertility but may have a
      parental-dependent effect on fetal programming with regard to placental
      development and fetal growth.

PMID- 24123571
TI  - Robotic single-access splenectomy using the Da Vinci Single-Site(r) platform: a
      case report.
AB  - BACKGROUND: Single-access laparoscopic splenectomy can offer patients some
      advantages. It has many difficulties, such as instrument clashing, lack of
      triangulation, odd angles and lack of space. The Da Vinci Single-Site(r) robotic
      surgery platform could decrease these difficulties. We present a case of single
      access robotic splenectomy using this device. METHODS: A 37 year-old female with
      idiopathic thrombocytopenic purpura was operated on with a single-site approach,
      using the Da Vinci Single-Site robotic surgery device. RESULTS: The procedure was
      successfully completed in 140 min. No intraoperative and postoperative
      complications occurred. The patient was discharged from hospital on day 3.
      CONCLUSIONS: Single-access robotic splenectomy seems to be feasible and safe
      using the new robotic single-access platform, which seems to overcome certain
      limits of previous robotic or conventional single-access laparoscopy. We think
      that additional studies should also be performed to explore the real cost
      effectiveness of the platform.

PMID- 24123572
TI  - Group additive values for the gas-phase standard enthalpy of formation, entropy
      and heat capacity of oxygenates.
AB  - A complete and consistent set of 60 Benson group additive values (GAVs) for
      oxygenate molecules and 97 GAVs for oxygenate radicals is provided, which allow
      to describe their standard enthalpies of formation, entropies and heat
      capacities. Approximately half of the GAVs for oxygenate molecules and the
      majority of the GAVs for oxygenate radicals have not been reported before. The
      values are derived from an extensive and accurate database of thermochemical data
      obtained by ab initio calculations at the CBS-QB3 level of theory for 202
      molecules and 248 radicals. These compounds include saturated and unsaturated,
      alpha- and beta-branched, mono- and bifunctional oxygenates. Internal rotations
      were accounted for by using one-dimensional hindered rotor corrections. The
      accuracy of the database was further improved by adding bond additive corrections
      to the CBS-QB3 standard enthalpies of formation. Furthermore, 14 corrections for
      non-nearest-neighbor interactions (NNI) were introduced for molecules and 12 for
      radicals. The validity of the constructed group additive model was established by
      comparing the predicted values with both ab initio calculated values and
      experimental data for oxygenates and oxygenate radicals. The group additive
      method predicts standard enthalpies of formation, entropies, and heat capacities
      with chemical accuracy, respectively, within 4 kJ mol(-1) and 4 J mol(-1) K(-1)
      for both ab initio calculated and experimental values. As an alternative, the
      hydrogen bond increment (HBI) method developed by Lay et al. (T. H. Lay, J. W.
      Bozzelli, A. M. Dean, E. R. Ritter, J. Phys. Chem.- 1995, 99, 14514) was used to
      introduce 77 new HBI structures and to calculate their thermodynamic parameters
      (Delta(f)H degrees , S degrees , C(p) degrees ). The GAVs reported in this work
      can be reliably used for the prediction of thermochemical data for large
      oxygenate compounds, combining rapid prediction with wide-ranging application.

PMID- 24123573
TI  - Ferns and lycopods--a potential treasury of anticancer agents but also a
      carcinogenic hazard.
AB  - Many species of seedless vascular plants-ferns and lycopods-have been used as
      food and folk medicine since ancient times. Some of them have become the focus of
      intensive research concerning their anticancer properties. Studies on the
      anticancer effect of crude extracts are being increasingly replaced by
      bioactivity-guided fractionation, as well as detailed assessment of the mechanism
      of action. Numerous compounds-especially flavonoids such as amentoflavone and
      protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and
      terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic,
      or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo
      experiments, some fern-derived compounds inhibited tumour growth with little
      toxicity. On the other hand, many ferns-not only the well-known Bracken
      (Pteridium)-may pose a significant hazard to human health due to the fact that
      they contain carcinogenic sesquiterpenoids and their analogues. The objective of
      this review is to summarise the recent state of research on the anticancer
      properties of ferns and lycopods, with a focus on their characteristic bioactive
      constituents. The carcinogenic hazard posed by ferns is also mentioned.

PMID- 24123574
TI  - Concerted two-electron transfer and high selectivity of TiO2 in photocatalyzed
      deoxygenation of epoxides.

PMID- 24123575
TI  - Tetrel-bonding interaction: rediscovered supramolecular force?
AB  - The w(hole) picture: A tetrel bond is a directional noncovalent interaction
      between a covalently bonded atom of Group IV and a negative site, for example,
      the lone pair of a Lewis base or an anion. It involves a region of positive
      electrostatic potential (sigma hole), and energetically, they are comparable to
      hydrogen bonds and other sigma-hole-based interactions. 

PMID- 24123576
TI  - Solvation of carbon dioxide in [C4 mim][BF(4)] and [C(4) mim][PF(6)] ionic
      liquids revealed by high-pressure NMR spectroscopy.
AB  - Where is CO2 ? The intermolecular interactions of [C4 mim]BF4 and [C4 mim]PF6
      ionic liquids and CO2 have been determined by high-pressure NMR spectroscopy in
      combination with molecular dynamic simulations. The anion and the cation are both
      engaged in interactions with CO2 . A detailed picture of CO2 solvation in these
      ILs is provided. CO2 solubility is essentially determined by the microscopic
      structure of the IL. 

PMID- 24123577
TI  - 'I divide life into different dimensions, one mental and one physical, to be able
      to handle life, you know?' Subjective accounts of the content of psychotic
      symptoms.
AB  - BACKGROUND: Previous research indicates that the content of psychotic symptoms is
      of significant importance for the individual who experiences them. However, there
      are limitations concerning the use of self-report instruments for capturing
      experiences that are of highly personal nature. The aim of this study was to
      provide a deeper understanding of how individuals with psychosis make sense of
      the content of their psychotic symptoms. METHOD: Semi-structured interviews were
      conducted with 12 individuals, some of whom were experiencing active symptoms and
      some of whom had experienced symptoms within the last 12 months. The interviews
      explored the individuals' understanding of psychotic symptoms in terms of the
      content and the possible meaning of the content. All participants were patients
      at a unit specializing in psychosis. The study applied interpretive
      phenomenological analyses to highlight the subjective understanding of the
      content of psychotic symptoms. RESULTS: Interpersonal experiences were a
      consistent theme in participants' understanding of the content of their psychotic
      symptoms. Grandiose content was understood as being related to lack of
      relationships and helplessness, whereas harassing content was related to
      experiences of being abused. Commanding content was linked to emotional
      consequences of intrusive relationships and to distressing life events.
      Supportive content was viewed as a substitute for real-life persons. CONCLUSIONS:
      These results support previous findings suggesting that the content of psychotic
      symptoms is related to interpersonal experiences. The study highlights the
      importance of validating the patient's own knowledge and interpretations of
      symptoms.

PMID- 24123578
TI  - Ultraflexible polymer solar cells using amorphous zinc-indium-tin oxide
      transparent electrodes.
AB  - Polymer solar cells are fabricated on highly conductive, transparent amorphous
      zinc indium tin oxide (a-ZITO) electrodes. For two representative active layer
      donor polymers, P3HT and PTB7, the power conversion efficiencies (PCEs) are
      comparable to reference devices using polycrystalline indium tin oxide (ITO)
      electrodes. Benefitting from the amorphous character of a-ZITO, the new devices
      are highly flexible and can be repeatedly bent to a radius of 5 mm without
      significant PCE reduction. 

PMID- 24123580
TI  - Evaluating the tropical forest carbon sink.

PMID- 24123579
TI  - Biallelic genome modification in F(0) Xenopus tropicalis embryos using the
      CRISPR/Cas system.
AB  - Gene inactivation is an important tool for correlation of phenotypic and genomic
      data, allowing researchers to infer normal gene function based on the phenotype
      when the gene is impaired. New and better approaches are needed to overcome the
      shortfalls of existing methods for any significant acceleration of scientific
      progress. We have adapted the CRISPR/Cas system for use in Xenopus tropicalis and
      report on the efficient creation of mutations in the gene encoding the enzyme
      tyrosinase, which is responsible for oculocutaneous albinism. Biallelic mutation
      of this gene was detected in the F0 generation, suggesting targeting efficiencies
      similar to that of TALENs. We also find that off-target mutagenesis seems to be
      negligible, and therefore, CRISPR/Cas may be a useful system for creating genome
      modifications in this important model organism.

PMID- 24123582
TI  - "On water", phosphine-free palladium-catalyzed room temperature C-H arylation of
      indoles.

PMID- 24123581
TI  - A DNA synthesis inhibitor is protective against proteotoxic stressors via
      modulation of fertility pathways in Caenorhabditis elegans.
AB  - Loss of germline precursor cells in C. elegans has previously been shown to
      improve protein homeostasis and extend lifespan, possibly due to reallocation of
      resources to somatic cells. In contrast, mutants that are sterile simply due to
      loss of sperm or oocyte production have a normal lifespan, often leading to the
      conclusion that loss of reproduction per se may have minor effects on C. elegans.
      We have found that inhibiting reproduction in C. elegans via the DNA synthesis
      inhibitor 5-fluoro-2-deoxyuridine (FUdR) improves protein homeostasis, stress
      resistance, and healthspan in wild-type animals. We find that FUdR is dependent
      on oogenesis and oocytic maturation. The effects of FUdR are dependent on FEM
      pathways, which regulate initiation of spermatogenesis. Loss of FEM expression
      leads to feminized animals that maintain arrested oocytes and are refractory to
      the effects of FUdR. FUdR-dependence is restored by spermatogenic signals, which
      trigger oocytic maturation and ovulation. Further, loss of FEM-3, a novel protein
      required for spermatogenesis, is sufficient to improve aspects of proteostasis.
      These effects are independent of previously described germline signals, including
      the DAF-16/FOXO, DAF-12/VDR, and HSF-1 pathways. These findings suggest that
      genetic or chemical inhibition of oocyte production can improve protein
      homeostasis in C. elegans. 

PMID- 24123583
TI  - Bone impacted fibular free flap: a novel technique to increase bone density for
      dental implantation in osseous reconstruction.
AB  - BACKGROUND: Fibular free flap (FFF) bone has thick cortical bone surrounding a
      fatty marrow. The cortex has sufficient density for dental implantation, but the
      marrow limits bone stock. A novel technique was devised to increase bone density:
      the bone-impacted fibular free flap (BIFFF). The purpose of this study was to:
      (1) describe the BIFFF technique; (2) evaluate the bone density of BIFFF; and (3)
      evaluate the stability/success of implants placed in BIFFFs. METHODS: Patients
      undergoing maxillary/mandibular reconstruction with FFFs were prospectively
      enrolled from 1998 to 2008. Two cohorts were compared: BIFFF and nonmodified FFF.
      The main outcome was bone density as seen on CT scans. Primary dental implant
      stability was determined via Periotest. RESULTS: Thirty-eight patients were
      included in this study. BIFFFs achieved higher bone density versus unmodified
      FFFs (p < .05). Greater primary dental implant stability occurred in BIFFFs (p <
      .05). One hundred percent of BIFFF and 59% of nonmodified FFF implants were
      successful at 1 year. CONCLUSION: BIFFF increases reconstructed bone density,
      initial dental implant stability, and 1-year implant success.

PMID- 24123584
TI  - Structure activity relationships of peptidic analogs of MyoD for the development
      of Id1 inhibitors as antiproliferative agents.
AB  - Id proteins, inhibitors of DNA binding proteins, have highly conserved
      dimerization motif known as the helix-loop-helix (HLH) domain that acts as a
      negative regulator of basic HLH (bHLH) transcription factors. In signaling
      pathways, Id proteins play an important role in cellular development,
      proliferation, and differentiation. The mechanism of Id proteins is to antagonize
      bHLH proteins, thereby preventing them from binding to DNA and inhibiting
      transcription of cellular differentiation-associated genes in cancer. Recently,
      we reported an inhibitor of Id1, peptide 3C, which showed good affinity to Id1
      protein and exhibited inhibitory effects in cancer cells. In this study, Ala (A)
      substituted analogs of peptide 3C were synthesized by SPPS, purified by RP-HPLC,
      and characterized by MALDI-TOF MS. Binding of each peptide to Id1 or Id1-HLH (the
      HLH domain of Id1) was monitored by surface plasmon resonance (SPR)-based
      biosensor. Biological effect of each peptide in MCF-7 breast cancer cells was
      analyzed by MTT cell viability assay. The secondary structure of substituted
      analogs of peptide 3C was investigated by circular dichroism (CD) spectroscopy.
      SPR results revealed that A-substituted analogs of peptide 3C showed weaker
      binding to Id1 than that of peptide 3C, indicating that the six amino acid
      residues in the N-terminal of peptide 3C were all essential for binding to Id1
      and the importance of amino acid residue was I(2)  > Q(6)  > Y(1)  > G(4)  > L(5)
      > E(3). In addition, substitution of E(3) in peptide 3C with D, Q, and R did not
      improve the binding potency of peptide 3C. MTT assay demonstrated that neither A
      substituted nor position 3-substituted analogs of peptide 3C showed increased
      antiproliferative effect in MCF-7 cancer cells. CD results indicated that peptide
      3C exhibited the highest content of alpha-helical structure (39.37%), suggesting
      that the alpha-helical structure may contribute to its binding potency for Id1
      and Id1-HLH. SAR results provided important information for the development of
      peptidic inhibitors of Id1 as anticancer agents and demonstrated peptide 3C as a
      promising lead for further modifications.

PMID- 24123585
TI  - Electrochemical synthesis of the aryl alpha-ketoesters from acetophenones
      mediated by KI.

PMID- 24123586
TI  - Regional variation in the utilisation of ambulatory services in Germany.
AB  - We used an administrative dataset covering approximately 90% of all Germans to
      investigate the determinants of regional differences in the utilisation of
      ambulatory services in the year 2008. There are great regional differences in
      Germany, in GP, specialist and psychotherapist consultations. By means of a
      regression model taking account of the spatial dependencies of the error terms,
      we can explain a considerable part of the variation in terms of differences in
      demography, health status and socio-economic features. In addition, we made use
      of data on pollutants, the supply of services and the number of hospital cases as
      explanatory variables, which all have a significant influence on utilisation but
      contribute considerably less to explaining the differences. Overall, we are in a
      position to explain 29-40% of the regional differences in ambulatory case numbers
      at the level of the 413 counties and 55-70% at the level of the 16 German states
      (Lander) by observable differences.

PMID- 24123587
TI  - Correlation between manual 0.2T MRI assessment of synovitis and EULAR-OMERACT
      scores of the wrist in patients with rheumatoid arthritis.
AB  - PURPOSE: To test the correlation between manually assessed volumes of magnetic
      resonance (MR) signal-enhancing regions in postcontrast images and MRI-based
      rheumatoid arthritis scoring system (RAMRIS) synovitis scores in 0.2T MR data.
      MATERIALS AND METHODS: The low-field (0.2T) extremity MRI scans were acquired in
      32 patients (37 study cases) as a part of the rheumatoid arthritis diagnostic
      procedure in accordance with Outcome Measures in Rheumatology Clinical Trials MRI
      working group (OMERACT) recommendations. The synovitis in joint regions was
      assessed based on RAMRIS. Regions of enhanced signals in postcontrast MR images
      were outlined manually. RESULTS: Spearman's rank-order correlations between
      RAMRIS scores and both absolute and relative volumes of signal-enhancing regions
      were equal to 0.68, 0.78 (moderately positive) and 0.84 (strongly positive) for
      distal radioulnar joint (DRUJ), intercarpal-carpometacarpal joints (ICCMJ), and
      radiocarpal joint (RCJ), respectively. Absolute and relative volumes of signal
      enhancing regions grow significantly with RAMRIS scores. CONCLUSION: Development
      of algorithms for automated detection of signal-enhancing regions in 0.2T MR
      images is a reasonable direction of forthcoming studies on computer-aided
      diagnosis (CAD) systems supporting low-field extremity MR-based diagnosis of
      rheumatoid arthritis by identifying its symptoms.

PMID- 24123593
TI  - Blood-flow streams in the fetal inferior vena cava: experimental animal study
      using ultrasound contrast agent.

PMID- 24123588
TI  - Pathogenic and obesogenic factors associated with inflammation in Chinese
      children, adolescents and adults.
AB  - OBJECTIVES: Influenced by pathogen exposure and obesity, inflammation provides a
      critical biological pathway linking changing environments to the development of
      cardiometabolic disease. This study tests the relative contribution of obesogenic
      and pathogenic factors to moderate and acute CRP elevations in Chinese children,
      adolescents and adults. METHODS: Data come from 8795 participants in the China
      Health and Nutrition Study. Age-stratified multinomial logistic models were used
      to test the association between illness history, pathogenic exposures, adiposity,
      health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and
      acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by
      household. Backward model selection was used to assess which pathogenic and
      obesogenic predictors remained independently associated with moderate and acute
      CRP levels when accounting for simultaneous exposures. RESULTS: Overweight was
      the only significant independent risk factor for moderate inflammation in
      children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08
      1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR
      1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87)
      were independently associated with a greater likelihood of moderate inflammation
      in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and
      overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute
      inflammation. Environmental pathogenicity was associated with a reduced
      likelihood of moderate inflammation, but a greater likelihood of acute
      inflammation in adults. CONCLUSIONS: These results highlight the importance of
      both obesogenic and pathogenic factors in shaping inflammation risk in societies
      undergoing nutritional and epidemiological transitions.

PMID- 24123594
TI  - Discovery of chemoselective and biocompatible reactions using a high-throughput
      immunoassay screening.

PMID- 24123595
TI  - Intense aversive training protects memory from the amnestic effects of
      hippocampal inactivation.
AB  - There is extensive evidence that amnestic treatments are less effective, or
      ineffective when administered to subjects that have been overtrained or subjected
      to high foot-shock intensities in aversively motivated learning. This protective
      effect has been found with a variety of learning tasks and with treatments that
      disrupt activity in several regions of the brain, including the hippocampus,
      amygdala, striatum, and substantia nigra. Such findings have been interpreted as
      suggesting that the brain regions disrupted are not critical sites for the memory
      processes induced by these types of training. In most experiments investigating
      this issue the amnestic treatments were administered after training. Thus, it
      might be less amnesia was induced because the training accelerated memory
      consolidation and, thus, the maximum effect of the amnestic treatment occurred
      after memory of the learning experience was consolidated. This study investigated
      this issue by inactivating the hippocampus of rats bilaterally with tetrodotoxin
      (TTX) (10 ng/side) 30 min before one-trial inhibitory avoidance training using
      relatively low (1.0 mA), medium (2.0 mA), or high (3.0 mA) foot-shock
      intensities. Retention of the task was measured 48 h after training. TTX produced
      a profound retention deficit, a mild deficit, and no deficit at all in the 1.0,
      2.0, and 3.0 mA groups, respectively. These data confirm the protective effect of
      training with relatively high foot-shock intensity against experimentally induced
      amnesia, and suggests that this protection is not due to accelerated
      consolidation. Rather, the findings suggest that strong training activates brain
      systems other than those typically involved in mediating memory consolidation.

PMID- 24123596
TI  - MMP-10 is required for efficient muscle regeneration in mouse models of injury
      and muscular dystrophy.
AB  - Matrix metalloproteinases (MMPs), a family of endopeptidases that are involved in
      the degradation of extracellular matrix components, have been implicated in
      skeletal muscle regeneration. Among the MMPs, MMP-2 and MMP-9 are upregulated in
      Duchenne muscular dystrophy (DMD), a fatal X-linked muscle disorder. However,
      inhibition or overexpression of specific MMPs in a mouse model of DMD (mdx) has
      yielded mixed results regarding disease progression, depending on the MMP
      studied. Here, we have examined the role of MMP-10 in muscle regeneration during
      injury and muscular dystrophy. We found that skeletal muscle increases MMP-10
      protein expression in response to damage (notexin) or disease (mdx mice),
      suggesting its role in muscle regeneration. In addition, we found that MMP-10
      deficient muscles displayed impaired recruitment of endothelial cells, reduced
      levels of extracellular matrix proteins, diminished collagen deposition, and
      decreased fiber size, which collectively contributed to delayed muscle
      regeneration after injury. Also, MMP-10 knockout in mdx mice led to a
      deteriorated dystrophic phenotype. Moreover, MMP-10 mRNA silencing in injured
      muscles (wild-type and mdx) reduced muscle regeneration, while addition of
      recombinant human MMP-10 accelerated muscle repair, suggesting that MMP-10 is
      required for efficient muscle regeneration. Furthermore, our data suggest that
      MMP-10-mediated muscle repair is associated with VEGF/Akt signaling. Thus, our
      findings indicate that MMP-10 is critical for skeletal muscle maintenance and
      regeneration during injury and disease.

PMID- 24123597
TI  - Liquiritigenin restores osteoblast damage through regulating oxidative stress and
      mitochondrial dysfunction.
AB  - We investigated the protective effect of liquiritigenin, one of the flavonoids
      present in Glycyrrhizae radix, against antimycin A-induced mitochondrial
      dysfunction in MC3T3-E1 osteoblast cells. Osteoblastic MC3T3-E1 cells were pre
      incubated with liquiritigenin before treatment with antimycin A, and markers of
      mitochondrial function and oxidative damage were examined. In addition, the
      effects of liquiritigenin on the activation of phosphoinositide 3-kinase (PI3K)
      were examined in MC3T3-E1 cells. Liquiritigenin protected MC3T3-E1 cells from
      antimycin A-induced cell death. However, the PI3K inhibitor, LY294002,
      significantly attenuated liquiritigenin-mediated cell survival, indicating the
      involvement of PI3K in the cytoprotective effect of liquiritigenin. Pretreatment
      with liquiritigenin prior to antimycin A exposure significantly reduced antimycin
      A-induced PI3K inactivation, mitochondrial membrane potential dissipation,
      complex IV inactivation, and ATP loss. Liquiritigenin also reduced mitochondrial
      superoxide generation, nitrotyrosine production, and cardiolipin peroxidation
      during mitochondrial complex inhibition with antimycin A. Taken together, the
      results of this study show that modulation of PI3K, antioxidant effects, and the
      attenuation of mitochondrial dysfunction by liquiritigenin represent an important
      mechanism for its protection of osteoblasts against cytotoxicity resulting from
      mitochondrial oxidative stress.

PMID- 24123598
TI  - T2*-correction in dynamic contrast-enhanced MRI from double-echo acquisitions.
AB  - PURPOSE: To evaluate the importance of T2*-effects on the arterial input function
      (AIF) and on the resulting dynamic parameter estimation in dynamic contrast
      enhanced (DCE) MRI of high-grade gliomas. MATERIALS AND METHODS: Seven patients
      with high-grade gliomas were imaged in total 50 times using a double-echo DCE
      sequence. Kinetic analysis using the extended Tofts model was performed using
      AIFs with and without correction for T2*-effects, and the resulting estimates of
      the transfer constant (K(trans) ), blood plasma volume (vp ), and the rate
      constant (kep ) were compared. Numerical simulations were done for comparison
      with clinical results as well as to further investigate the dependency of
      parameter values on the magnitude of T2*-induced errors. RESULTS: All kinetic
      parameters were found to be overestimated if T2*-effects in the AIF were not
      accounted for; with vp being most severely affected. The relative error in each
      parameter was dependent on the absolute parameter magnitude, resulting in
      incorrect parametric tumor distributions in the presence of uncorrected AIF T2*
      effects. CONCLUSION: In DCE, a sufficiently short echo time should be used or
      corrections for T2*-effects based on double-echo acquisition should be made for
      correct quantification of kinetic parameters.

PMID- 24123599
TI  - New semi-synthesis of ubiquitin C-terminal conjugate with 7-amino-4
      methylcoumarin.
AB  - The ligation of peptide hydrazides at a Gly site carrying a removal auxiliary was
      found to be an efficient process. This technology was successfully used for the
      synthesis of ubiquitin C-terminal conjugates. Recombinant Ub(1-75)-NHNH2 was
      prepared through the hydrozinolysis of the Ub(1-75)-intein fusion protein. It was
      ligated with a glycine derivative modified with an acid-sensitive thiol
      auxiliary. The final acid treatment produced the desired bioactive ubiquitin
      conjugates in practical quantities. Thus, the method described here extends the
      protocols of expressed protein ligation.

PMID- 24123600
TI  - High imatinib dose overcomes insufficient response associated with ABCG2
      haplotype in chronic myelogenous leukemia patients.
AB  - Pharmacogenetic studies in chronic myelogenous leukemia (CML) typically use a
      candidate gene approach. In an alternative strategy, we analyzed the impact of
      single nucleotide polymorphisms (SNPs) in drug transporter genes on the molecular
      response to imatinib, using a DNA chip containing 857 SNPs covering 94 drug
      transporter genes. Two cohorts of CML patients treated with imatinib were
      evaluated: an exploratory cohort including 105 patients treated at 400 mg/d and a
      validation cohort including patients sampled from the 400 mg/d and 600 mg/d arms
      of the prospective SPIRIT trial (n=239). Twelve SNPs discriminating patients
      according to cumulative incidence of major molecular response (CI-MMR) were
      identified within the exploratory cohort. Three of them, all located within the
      ABCG2 gene, were validated in patients included in the 400 mg/d arm of the SPIRIT
      trial. We identified an ABCG2 haplotype (define as G-G, rs12505410 and rs2725252)
      as associated with significantly higher CI-MMR in patients treated at 400 mg/d.
      Interestingly, we found that patients carrying this ABCG2 "favorable" haplotype
      in the 400 mg arm reached similar CI-MMR rates that patients randomized in the
      imatinib 600 mg/d arm. Our results suggest that response to imatinib may be
      influenced by constitutive haplotypes in drug transporter genes. Lower response
      rates associated with "non- favorable" ABCG2 haplotypes may be overcome by
      increasing the imatinib daily dose up to 600 mg/d. 

PMID- 24123601
TI  - Impact of repetitive exposure to strong static magnetic fields on pregnancy and
      embryonic development of mice.
AB  - PURPOSE: To evaluate possible risks of strong static magnetic fields for embryo
      implantation, gestation, organogenesis, and embryonic development. MATERIALS AND
      METHODS: Pregnant mice were exposed for 75 minutes daily during the entire course
      of pregnancy at the bore entrance, representing the position of medical staff,
      and at the isocenter, representing the position of patients, of a 1.5 T and a 7 T
      human MRI scanner. RESULTS: No effect of static magnetic field strength was
      observed with regard to pregnancy rate, duration of pregnancy, litter size, still
      births, malformations, sex distribution, or postpartum death of offspring. During
      the first 8 weeks postnatal, mice exposed in utero to a magnetic field strength
      of 1.5 T or stronger showed a slight delay in weight gain and in time to eye
      opening compared to controls. CONCLUSION: Daily exposure to strong magnetic
      fields during pregnancy had no deleterious effect on offspring; however, a
      developmental retardation could be observed postnatally with regard to weight
      gain and eye opening.

PMID- 24123602
TI  - [3]Dendralene synthesis: rhodium(III)-catalyzed alkenyl C-H activation and
      coupling reaction with allenyl carbinol carbonate.
AB  - [3]DendrAl(l)ene! A new synthesis of [3]dendralenes is based on a Rh(III) 
      catalyzed alkenyl C?H activation and coupling reaction with allenyl carbinol
      carbonates (see scheme; DG=directing group). A variety of [3]dendralenes with
      diverse substitution patterns are accessible with good efficiency. The reaction
      is highly stereoselective and compatible with different directing groups and
      numerous functional groups. 

PMID- 24123603
TI  - Radiographic extracapsular extension and treatment outcomes in locally advanced
      oropharyngeal carcinoma.
AB  - BACKGROUND: Pathologic extracapsular extension (pECE) in metastatic lymph nodes
      is associated with poor prognosis for oropharyngeal carcinoma. The prognostic
      value of radiographic extracapsular extension (rECE) has not been studied.
      METHODS: A retrospective analysis was conducted of 111 patients with locally
      advanced oropharyngeal carcinoma treated in the Mount Sinai Radiation Oncology
      Department with accessible pretreatment CT reports. Univariate Kaplan-Meier and
      multivariate Cox regression analyses compared cohorts for locoregional control,
      distant control, progression-free (PFS), and overall survival (OS). RESULTS:
      Sixty-four patients had rECE-present and 47 had rECE-absent scans. The patients
      with rECE presence had significantly worse OS (3-year: 95% vs 77%; p = .006), PFS
      (3-year: 91% vs 71%; p = .002), and distant control (3-year: 98% vs 81%; p =
      .008), with no difference in locoregional control. On multivariate analysis, rECE
      presence was a negative prognosticator for OS, PFS, and distant control.
      CONCLUSION: This study suggests that rECE is an independent prognosticator of
      poor distant control and survival with little impact on locoregional control for
      oropharyngeal carcinoma.

PMID- 24123604
TI  - Formation of quaternary stereogenic centers by copper-catalyzed asymmetric
      conjugate addition reactions of alkenylaluminums to trisubstituted enones.
AB  - Alkenylaluminums undergo asymmetric copper-catalyzed conjugate addition (ACA) to
      beta-substituted enones allowing the formation of stereogenic all-carbon
      quaternary centers. Phosphinamine-copper complexes proved to be particularly
      active and selective compared with phosphoramidite ligands. After extensive
      optimization, high enantioselectivities (up to 96% ee) were obtained for the
      addition of alkenylalanes to beta-substituted enones. Two strategies for the
      generation of the requisite alkenylaluminums were explored allowing for the
      introduction of aryl- and alkyl-substituted alkenyl nucleophiles. Moreover, alkyl
      substituted phosphinamine (SimplePhos) ligands were identified for the first time
      as highly efficient ligands for the Cu-catalyzed ACA.

PMID- 24123605
TI  - Enhanced electrophoretic motion using supercapacitor-based energy storage system.
AB  - Electrophoretic motion at low potentials is facilitated by redox chemistry
      occurring in a supercapacitor-based electrochemical energy storage system during
      charge and discharge. We show that MnO2 -modified electrodes can effectively
      alleviate the electrode surface polarization, the main factor that leads to
      inefficient electrophoresis at low voltages. A self-powered electrophoretic
      system based on a discharging battery has been also fabricated. 

PMID- 24123606
TI  - Computation and visualization of uncertainty in surgical navigation.
AB  - BACKGROUND: Surgical displays do not show uncertainty information with respect to
      the position and orientation of instruments. Data is presented as though it were
      perfect; surgeons unaware of this uncertainty could make critical navigational
      mistakes. METHODS: The propagation of uncertainty to the tip of a surgical
      instrument is described and a novel uncertainty visualization method is proposed.
      An extensive study with surgeons has examined the effect of uncertainty
      visualization on surgical performance with pedicle screw insertion, a procedure
      highly sensitive to uncertain data. RESULTS: It is shown that surgical
      performance (time to insert screw, degree of breach of pedicle, and rotation
      error) is not impeded by the additional cognitive burden imposed by uncertainty
      visualization. CONCLUSIONS: Uncertainty can be computed in real time and
      visualized without adversely affecting surgical performance, and the best method
      of uncertainty visualization may depend upon the type of navigation display.

PMID- 24123607
TI  - Elevation-induced climate change as a dominant factor causing the late Miocene
      C(4) plant expansion in the Himalayan foreland.
AB  - During the late Miocene, a dramatic global expansion of C4 plant distribution
      occurred with broad spatial and temporal variations. Although the event is well
      documented, whether subsequent expansions were caused by a decreased atmospheric
      CO2 concentration or climate change is a contentious issue. In this study, we
      used an improved inverse vegetation modeling approach that accounts for the
      physiological responses of C3 and C4 plants to quantitatively reconstruct the
      paleoclimate in the Siwalik of Nepal based on pollen and carbon isotope data. We
      also studied the sensitivity of the C3 and C4 plants to changes in the climate
      and the atmospheric CO2 concentration. We suggest that the expansion of the C4
      plant distribution during the late Miocene may have been primarily triggered by
      regional aridification and temperature increases. The expansion was unlikely
      caused by reduced CO2 levels alone. Our findings suggest that this abrupt
      ecological shift mainly resulted from climate changes related to the decreased
      elevation of the Himalayan foreland. 

PMID- 24123608
TI  - Is the medical loss ratio a good target measure for regulation in the individual
      market for health insurance?
AB  - Effective January 1, 2011, individual market health insurers must meet a minimum
      medical loss ratio (MLR) of 80%. This law aims to encourage 'productive' forms of
      competition by increasing the proportion of premium dollars spent on clinical
      benefits. To date, very little is known about the performance of firms in the
      individual health insurance market, including how MLRs are related to insurer and
      market characteristics. The MLR comprises one component of the price-cost margin,
      a traditional gauge of market power; the other component is percent of premiums
      spent on administrative expenses. We use data from the National Association of
      Insurance Commissioners (2001-2009) to evaluate whether the MLR is a good target
      measure for regulation by comparing the two components of the price-cost margin
      between markets that are more competitive versus those that are not, accounting
      for firm and market characteristics. We find that insurers with monopoly power
      have lower MLRs. Moreover, we find no evidence suggesting that insurers'
      administrative expenses are lower in more concentrated insurance markets. Thus,
      our results are largely consistent with the interpretation that the MLR could
      serve as a target measure of market power in regulating the individual market for
      health insurance but with notable limited ability to capture product and firm
      heterogeneity.

PMID- 24123609
TI  - Development and external validation of new ultrasound-based mathematical models
      for preoperative prediction of high-risk endometrial cancer.
AB  - OBJECTIVES: To develop and validate strategies, using new ultrasound-based
      mathematical models, for the prediction of high-risk endometrial cancer and
      compare them with strategies using previously developed models or the use of
      preoperative grading only. METHODS: Women with endometrial cancer were
      prospectively examined using two-dimensional (2D) and three-dimensional (3D) gray
      scale and color Doppler ultrasound imaging. More than 25 ultrasound, demographic
      and histological variables were analyzed. Two logistic regression models were
      developed: one 'objective' model using mainly objective variables; and one
      'subjective' model including subjective variables (i.e. subjective impression of
      myometrial and cervical invasion, preoperative grade and demographic variables).
      The following strategies were validated: a one-step strategy using only
      preoperative grading and two-step strategies using preoperative grading as the
      first step and one of the new models, subjective assessment or previously
      developed models as a second step. RESULTS: One-hundred and twenty-five patients
      were included in the development set and 211 were included in the validation set.
      The 'objective' model retained preoperative grade and minimal tumor-free
      myometrium as variables. The 'subjective' model retained preoperative grade and
      subjective assessment of myometrial invasion. On external validation, the
      performance of the new models was similar to that on the development set.
      Sensitivity for the two-step strategy with the 'objective' model was 78% (95% CI,
      69-84%) at a cut-off of 0.50, 82% (95% CI, 74-88%) for the strategy with the
      'subjective' model and 83% (95% CI, 75-88%) for that with subjective assessment.
      Specificity was 68% (95% CI, 58-77%), 72% (95% CI, 62-80%) and 71% (95% CI, 61
      79%) respectively. The two-step strategies detected up to twice as many high-risk
      cases as preoperative grading only. The new models had a significantly higher
      sensitivity than did previously developed models, at the same specificity.
      CONCLUSION: Two-step strategies with 'new' ultrasound-based models predict high
      risk endometrial cancers with good accuracy and do this better than do previously
      developed models.

PMID- 24123611
TI  - Ionic liquid crystals derived from amino acids.
AB  - Novel chiral amino acid derived ionic liquid crystals with amine and amide
      moieties as spacers between the imidazolium head group and the alkyl chain were
      synthesised. The key step in the synthesis utilised the relatively uncommon SO3
      leaving group in a microwave-assisted reaction. The mesomorphic properties of the
      mesogens were determined by differential scanning calorimetry (DSC), polarising
      optical microscopy (POM) and X-ray diffraction. All liquid crystalline salts
      exhibit a smectic A mesophase geometry with strongly interdigitated bilayer
      structures. An increase of the steric bulk of the stereogenic centre hindered the
      formation of mesophases. In case of phenylalanine-derived derivatives a
      mesomorphic behaviour was observed for shorter alkyl chains as compared to other
      amino acid derivatives indicating an additional stabilising effect by the phenyl
      moiety.

PMID- 24123610
TI  - Novel tripod amphiphiles for membrane protein analysis.
AB  - Integral membrane proteins play central roles in controlling the flow of
      information and molecules across membranes. Our understanding of membrane protein
      structures and functions, however, is seriously limited, mainly due to
      difficulties in handling and analysing these proteins in aqueous solution. The
      use of a detergent or other amphipathic agents is required to overcome the
      intrinsic incompatibility between the large lipophilic surfaces displayed by the
      membrane proteins in their native forms and the polar solvent molecules. Here, we
      introduce new tripod amphiphiles displaying favourable behaviours toward several
      membrane protein systems, leading to an enhanced protein solubilisation and
      stabilisation compared to both conventional detergents and previously described
      tripod amphiphiles. 

PMID- 24123612
TI  - Enantiospecific total synthesis of N-methylwelwitindolinone D isonitrile.
AB  - The total synthesis of N-methylwelwitindolinone D isonitrile (1) has been
      achieved in 17 steps from a readily available carvone derivative. The route
      features a double C-H functionalization event involving a keto oxindole substrate
      to introduce the tetrahydrofuran ring of the natural product. 

PMID- 24123613
TI  - Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus
      tropicalis.
AB  - We have assessed the efficacy of the recently developed CRISPR/Cas (clustered
      regularly interspaced short palindromic repeats/CRISPR-associated) system for
      genome modification in the amphibian Xenopus tropicalis. As a model experiment,
      targeted mutations of the tyrosinase gene were verified, showing the expected
      albinism phenotype in injected embryos. We further tested this technology by
      interrupting the six3 gene, which is required for proper eye and brain formation.
      Expected eye and brain phenotypes were observed when inducing mutations in the
      six3 coding regions, as well as when deleting the gene promoter by dual
      targeting. We describe here a standardized protocol for genome editing using this
      system. This simple and fast method to edit the genome provides a powerful new
      reverse genetics tool for Xenopus researchers.

PMID- 24123614
TI  - Atypical structural and pi-electron features of a melanin polymer that lead to
      superior free-radical-scavenging properties.

PMID- 24123615
TI  - The hippocampus uses information just encountered to guide efficient ongoing
      behavior.
AB  - Adaptive ongoing behavior requires using immediate sensory input to guide
      upcoming actions. Using a novel paradigm with volitional exploration of visuo
      spatial scenes, we revealed novel deficits among hippocampal amnesic patients in
      effective spatial exploration of scenes, indicated by less-systematic exploration
      patterns than those of healthy comparison subjects. The disorganized exploration
      by amnesic patients occurred despite successful retention of individual object
      locations across the entire exploration period, indicating that exploration
      impairments were not secondary to rapid decay of scene information. These
      exploration deficits suggest that amnesic patients are impaired in integrating
      memory for recent actions, which may include information such as locations just
      visited and scene content, to plan immediately forthcoming actions. Using a novel
      task that measured the on-line links between sensory input and behavior, we
      observed the critical role of the hippocampus in modulating ongoing behavior.

PMID- 24123616
TI  - Physiological oxygen prevents frequent silencing of the DLK1-DIO3 cluster during
      human embryonic stem cells culture.
AB  - Genetic and epigenetic alterations are observed in long-term culture (>30
      passages) of human embryonic stem cells (hESCs); however, little information is
      available in early cultures. Through a large-scale gene expression analysis
      between initial-passage hESCs (ihESCs, <10 passages) and early-passage hESCs
      (ehESCs, 20-30 passages) of 12 hESC lines, we found that the DLK1-DIO3 gene
      cluster was normally expressed and showed normal methylation pattern in ihESC,
      but was frequently silenced after 20 passages. Both the DLK1-DIO3 active status
      in ihESCs and the inactive status in ehESCs were inheritable during
      differentiation. Silencing of the DLK1-DIO3 cluster did not seem to compromise
      the multilineage differentiation ability of hESCs, but was associated with
      reduced DNA damage-induced apoptosis in ehESCs and their differentiated
      hepatocyte-like cell derivatives, possibly through attenuation of the expression
      and phosphorylation of p53. Furthermore, we demonstrated that 5% oxygen, instead
      of the commonly used 20% oxygen, is required for preserving the expression of the
      DLK1-DIO3 cluster. Overall, the data suggest that active expression of the DLK1
      DIO3 cluster represents a new biomarker for epigenetic stability of hESCs and
      indicates the importance of using a proper physiological oxygen level during the
      derivation and culture of hESCs.

PMID- 24123617
TI  - Effect of Terminalia chebula extract and chlorhexidine on salivary pH and
      periodontal health: 2 weeks randomized control trial.
AB  - A double blind, randomized, controlled study with three parallel treatment groups
      was done to evaluate the efficacy of a Terminalia chebula 10% mouth rinse
      compared with chlorhexidine 0.12% mouth rinse, applied two times daily for 2
      weeks, in the treatment of dental plaque and gingivitis. Seventy-eight patients
      were included in the study. The efficacy variables were periodontal indices on
      days 0, 7 and 14 after commencement of therapy. Twenty six patients received
      chlorhexidine mouth rinse, twenty six Terminalia chebula mouth rinse and twenty
      six received saline solution. The clinical parameters were significantly reduced
      by both chlorhexidine and Terminalia chebula mouth rinse although no significant
      difference was seen between the two groups (P > 0.05). This study demonstrated
      that Terminalia chebula mouth rinse is effective in reducing microbial plaque,
      gingival inflammation and neutralizing salivary pH.

PMID- 24123618
TI  - Self-assembly of pH and calcium dual-responsive peptide-amphiphilic hydrogel.
AB  - Peptide-based hydrogels have gained much interest for biomedical applications as
      a result of their biocompatibility. Herein, we reported a synthetic pH-sensitive
      and calcium-responsive peptide-amphiphilic hydrogel. The sequences of the peptide
      amphiphiles were derived from the repeat-in-toxin (RTX) motif. At a certain
      peptide-amphiphile concentration, self-assembly was accompanied by the formation
      of a rigid, viscoelastic hydrogel at low pH or the presence of calcium ions.
      Circular dichroism spectra showed that the peptide amphiphiles adopted beta-sheet
      structure. Meanwhile, as revealed by transmission electron microscopy, the
      peptide-amphiphile self-assembly was accompanied by the formation of long
      interconnected nanofibrillar superstructure. Material properties of the resulting
      peptide-amphiphile hydrogel were characterized using oscillatory sheer rheology,
      and the storage modulus (G') was found to be one order of magnitude higher than
      the loss modulus (G"), indicating a moderately rigid viscoelastic material.
      Furthermore, with systematical residue substitution, it was found that the
      aspartic acid within the repeat-in-toxin sequence of peptide amphiphiles was
      responsible for the pH and calcium selectivity. The environmental responsiveness,
      secondary structure, morphology, and mechanical nature of the peptide-amphiphile
      hydrogel make it a possible material candidate for biomedical and engineering
      application.

PMID- 24123619
TI  - The deubiquitinating enzyme USP17 is associated with non-small cell lung cancer
      (NSCLC) recurrence and metastasis.
AB  - USP17 is a cell cycle regulated deubiquitinating enzyme that is highly expressed
      in tumor-derived cell lines and has an established role in cell proliferation and
      chemotaxis. This is the first study to examine the clinical significance of USP17
      expression in non-small cell lung cancer (NSCLC). USP17 was overexpressed in both
      squamous and adenocarcinoma NSCLC tissue. Patients with USP17 positive tumors had
      significantly reduced recurrence-free survival than patients with USP17 negative
      tumors. Moreover, USP17 was more highly expressed in patients with recurrence of
      disease at distant sites, suggesting that USP17 levels may correlate with NSCLC
      distant metastases. Overall, these findings establish USP17 as a potentially
      valuable novel biomarker for metastatic lung cancer. 

PMID- 24123620
TI  - Quantitative measurement of synthetic cathinones in oral fluid.
AB  - Synthetic cathinones have recently emerged as a substitute for common drugs of
      abuse. Synthetic cathinones can elicit powerful adverse effects such as
      delusions, hallucinations and potentially dangerous behavior. To develop a method
      to analyze 10 synthetic cathinones in oral fluid, we implemented a combined
      approach of solid-phase extraction and ultra-high-performance liquid
      chromatography-tandem mass spectrometry. The developed analytical procedure was a
      sensitive, precise and selective method suited for high-throughput toxicological
      screening of synthetic cathinones. The method was validated using standard
      parameters including accuracy, precision, linearity, sensitivity, matrix effect
      and recovery. Human subject samples were analyzed using the developed method to
      demonstrate the applicability of the method. 

PMID- 24123621
TI  - Opioid overdose mortality in Kansas, 2001-2011: toxicologic evaluation of intent.
AB  - Drug concentration is a factor in the determination of the manner of death, but
      considerable overlap exists between therapeutic and toxic concentrations. This
      study aims to quantify opioid mortality in Kansas from use of fentanyl, methadone
      and oxycodone and to evaluate utility of drug concentrations for the
      determination of the manner of death. Cases referred to a forensic pathology
      practice in Kansas for autopsy from 1 January 2001 to 31 December 2011 were
      considered. The criterion for inclusion was detection of fentanyl, methadone
      and/or oxycodone in postmortem toxicology. Of 9,789 cases, 3,315 had positive
      toxicology: 180 of fentanyl, 299 of methadone and 310 of oxycodone. There were
      207 single opioid fatalities, 264 polydrug overdoses and 318 deaths where an
      opioid was present but not contributory to the mechanism of death. In line with
      published studies, incidence of opioid overdose deaths increased over the time of
      the study. Drug concentrations within each cause and manner of death covered
      broad ranges. Non-natural and natural manners had less overlap than existed
      within non-natural manners in limited comparisons. This study shows that drug
      concentration is independent of manner for non-natural deaths and although
      insufficient to identify intent, can provide a guideline in differentiating non
      natural from natural deaths. 

PMID- 24123626
TI  - Three-dimensional solvent-vapor map generated by supramolecular metal-complex
      entrapment.

PMID- 24123627
TI  - Reaction-based and single fluorescent emitter decorated ratiometric nanoprobe to
      detect hydrogen peroxide.
AB  - A novel reaction-based cross-linked polymeric nanoprobe with a self-calibrating
      ratiometric fluorescence readout to selectively detect H2O2 is reported. The
      polymeric nanoprobe is fabricated by using hydrophobic H2O2-reactive boronic
      ester groups, crosslinker units, and environmentally sensitive 3-hydroxyflavone
      fluorophores through a miniemulsion polymerization. On treatment with H2O2, the
      boronic esters in the polymer are cleaved to form hydrophilic alcohols and
      subsequently lead to a hydrophobic-hydrophilic transition. Covalently linked 3
      hydroxyflavones manifest the change in polarity as a ratiometric transition from
      green to blue, accompanied by a 500-fold increase in volume. Furthermore, this
      nanoprobe has been used for ratiometric sensing of glucose by monitoring the H2O2
      generated during the oxidation of glucose by glucose oxidase, and thus
      successfully distinguished between normal and pathological levels of glucose.

PMID- 24123628
TI  - Measuring overfitting in nonlinear models: a new method and an application to
      health expenditures.
AB  - When fitting an econometric model, it is well known that we pick up part of the
      idiosyncratic characteristics of the data along with the systematic relationship
      between dependent and explanatory variables. This phenomenon is known as
      overfitting and generally occurs when a model is excessively complex relative to
      the amount of data available. Overfitting is a major threat to regression
      analysis in terms of both inference and prediction. We start by showing that the
      Copas measure becomes confounded by shrinkage or expansion arising from in-sample
      bias when applied to the untransformed scale of nonlinear models, which is
      typically the scale of interest when assessing behaviors or analyzing policies.
      We then propose a new measure of overfitting that is both expressed on the scale
      of interest and immune to this problem. We also show how to measure the
      respective contributions of in-sample bias and overfitting to the overall
      predictive bias when applying an estimated model to new data. We finally
      illustrate the properties of our new measure through both a simulation study and
      a real-data illustration based on inpatient healthcare expenditure data, which
      shows that the distinctions can be important.

PMID- 24123629
TI  - Comparison of the initial surgical experience with robotic and laparoscopic
      myomectomy.
AB  - OBJECTIVE: To compare the initial surgical outcomes of robotic and laparoscopic
      myomectomy in patients with symptomatic uterine myomas. STUDY DESIGN:
      Retrospective chart review of 86 patients undergoing robotic (RM) (n = 43) or
      laparoscopic (LM) (n = 43) myomectomy. Data included fibroid characteristics
      (number, weight, location) layers of uterine reconstruction, operating time,
      blood loss, complications, and postoperative hospital stay. RESULTS: No
      significant differences were noted between RM and LM for fibroid number and
      weight and mean operating time, although the number of patients receiving at
      least a double-layer uterine reconstruction was higher in RM than LM. Blood loss
      was higher after LM, while no differences resulted in hospital stay. CONCLUSION:
      RM may have some additional advantages compared with LM in terms of bleeding and
      uterine suturing without compromising operation duration, at least when surgeons
      were at the beginning of their experience of endoscopic treatment of symptomatic
      uterine myomas.

PMID- 24123630
TI  - Selective visualization of rabbit knee cartilage using MR imaging with a double
      contrast agent.
AB  - PURPOSE: To establish a reliable method and efficient contrast agent for
      selective MR imaging of articular cartilage to improve the diagnosis of cartilage
      disorders. MATERIALS AND METHODS: A standard trace element replenisher (Mineric),
      which includes manganese chloride, cupric sulfate (both positive MR contrast
      agents), and colloidal ferric chloride (a negative contrast agent), was evaluated
      in comparison with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) as a
      potential contrast agent. Normal saline was used as a control. The agents were
      injected into bilateral knee joints, and the entire joint block was dissected.
      Coronal images of femorotibial joints were obtained at 7.05 Tesla. Signal
      intensity ratios (SIRs) of cartilage to joint fluid were calculated for T1 and T2
      values. The side effects of the agents were also investigated. Finally,
      histological evaluations were performed. RESULTS: SIRs were significantly
      increased in the Mineric treatment group compared with the Gd-DTPA and saline
      treatment groups. The T1 values of cartilage and fluid were significantly
      decreased in the Gd-DTPA and Mineric treatment groups. The T2 values of fluid
      were significantly decreased in the Mineric treatment group. No apparent side
      effects or degenerative changes in the joints were observed. CONCLUSION: A
      clinical trace element mixture was used as a novel double-contrast agent, and it
      exhibits selective MR contrast in articular cartilage.

PMID- 24123633
TI  - Association between reduced fetal movements at term and abnormal uterine artery
      Doppler indices.
AB  - OBJECTIVES: To evaluate the association between second-trimester uterine artery
      (UtA) Doppler pulsatility index (PI) with reduced fetal movements (RFM) and
      adverse pregnancy outcome at term. METHODS: This was a retrospective cohort study
      of all singleton pregnancies referred for routine antenatal care at a fetal
      medicine unit over a 5-year period. UtA Doppler indices were obtained at the time
      of the routine anomaly scan between 19 and 23 weeks' gestation to assess the risk
      for pre-eclampsia. All episodes of RFM within 1 month of the expected date of
      delivery were recorded. Regression and sensitivity analyses were used to assess
      the relationship between UtA-PI with RFM, small-for-gestational-age (SGA) fetuses
      and stillbirth after 36 weeks' gestation. RESULTS: Overall, 17, 649 pregnancies
      were included in the analysis, of which 742 presented with RFM, 1494 gave birth
      to an SGA newborn and 53 were complicated by stillbirth after 36 weeks'
      gestation. Logistic regression analysis showed a significant and independent
      association between UtA-PI and RFM (odds ratio (OR), 5.03 (95% CI, 4.21-6.01); P
      < 0.001), SGA (OR 2.41 (95% CI, 2.09-2.79); P < 0.001) and stillbirth (OR 1.55
      (95% CI, 1.21-1.98); P< 0.001). The association between UtA-PI and SGA was
      significantly stronger in women presenting with RFM than in the rest of the
      cohort (P < 0.001). Similarly the association between UtA-PI and RFM was
      significantly stronger in those pregnancies complicated by stillbirth (P <
      0.001). CONCLUSIONS: Compared with normal pregnancies, those complicated by RFM,
      SGA and stillbirth at term had higher UtA-PI at 19-23 weeks' gestation. These
      findings support the assertion that RFM at term is independently related to
      placental dysfunction and subsequent risk for SGA and stillbirth.

PMID- 24123635
TI  - Porphyrins fused to N-heterocyclic carbenes (NHCs): modulation of the electronic
      and catalytic properties of NHCs by the central metal of the porphyrin.
AB  - We report herein a detailed study of the use of porphyrins fused to imidazolium
      salts as precursors of N-heterocyclic carbene ligands 1 M. Rhodium(I) complexes 6
      M-9 M were prepared by using 1 M ligands with different metal cations in the
      inner core of the porphyrin (M=Ni(II) , Zn(II) , Mn(III) , Al(III) , 2H). The
      electronic properties of the corresponding N-heterocyclic carbene ligands were
      investigated by monitoring the spectroscopic changes occurring in the cod and CO
      ancillary ligands of [(1 M)Rh(cod)Cl] and [(1 M)Rh(CO)2 Cl] complexes (cod=1,5
      cyclooctadiene). Porphyrin-NHC ligands 1 M with a trivalent metal cation such as
      Mn(III) and Al(III) are overall poorer electron donors than porphyrin-NHC ligands
      with no metal cation or incorporating a divalent metal cation such as Ni(II) and
      Zn(II) . Imidazolium salts 3 M (M=Ni, Zn, Mn, 2H) have also been used as NHC
      precursors to catalyze the ring-opening polymerization of L-lactide. The results
      clearly show that the inner metal of the porphyrin has an important effect on the
      reactivity of the outer carbene. 

PMID- 24123634
TI  - Thiols and selenols as electron-relay catalysts for disulfide-bond reduction.
AB  - Pass them on! Dithiobutylamine immobilized on a resin is a useful reagent for the
      reduction of disulfide bonds. Its ability to reduce a disulfide bond in a protein
      is enhanced greatly if used along with a soluble strained cyclic disulfide or
      mixed diselenide that relays electrons from the resin to the protein. This
      electron-relay catalysis system provides distinct advantages over the use of
      excess soluble reducing agent alone. 

PMID- 24123636
TI  - In situ studies of phase separation and crystallization directed by Marangoni
      instabilities during spin-coating.
AB  - Results of a pioneering study are presented in which for the first time,
      crystallization, phase separation and Marangoni instabilities occurring during
      the spin-coating of polymer blends are directly visualized, in real-space and
      real-time. The results provide exciting new insights into the process of self
      assembly, taking place during spin-coating, paving the way for the rational
      design of processing conditions, to allow desired morphologies to be obtained. 

PMID- 24123637
TI  - Threefold cross-linked polystyrene-triphenylphosphane hybrids: mono-P-ligating
      behavior and catalytic applications for aryl chloride cross-coupling and C(sp(3))
      H borylation.
AB  - Covalently bound polystyrene-phosphane hybrids were prepared by a method based on
      radical emulsion polymerization of styrenes in the presence of a tris(p
      vinylphenyl)phosphane cross-linker. These hybrids favor mono-P-ligation to
      transition-metal complexes and are useful for challenging catalysis, such as Pd
      catalyzed C?C/C?N couplings with unactivated chloroarenes and Ir- or Rh-catalyzed
      C(sp(3) )?H borylations. 

PMID- 24123638
TI  - Improved motion correction in PROPELLER by using grouped blades as reference.
AB  - PURPOSE: To develop a robust reference generation method for improving PROPELLER
      (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction)
      reconstruction. MATERIALS AND METHODS: A new reference generation method, grouped
      blade reference (GBR), is proposed for calculating rotation angle and translation
      shift in PROPELLER. Instead of using a single-blade reference (SBR) or combined
      blade reference (CBR), our method classifies blades by their relative
      correlations and groups similar blades together as the reference to prevent
      inconsistent data from interfering the correction process. Numerical simulations
      and in vivo experiments were used to evaluate the performance of GBR for
      PROPELLER, which was further compared with SBR and CBR in terms of error level
      and computation cost. RESULTS: Both simulation and in vivo experiments
      demonstrate that GBR-based PROPELLER provides better correction for random motion
      or bipolar motion comparing with SBR or CBR. It not only produces images with
      lower error level but also needs less iteration steps to converge. CONCLUSION: A
      grouped-blade for reference selection was investigated for PROPELLER MRI. It
      helps to improve the accuracy and robustness of motion correction for various
      motion patterns.

PMID- 24123639
TI  - TLR ligands stimulation protects MSC from NK killing.
AB  - Mesenchymal stem cells (MSCs) play a fundamental role in allograft rejection and
      graft-versus-host disease through their immunosuppressive abilities. Recently,
      Toll-like receptors (TLR) have been shown to modulate MSC functions. The aim of
      this study was to investigate the effects of several TLR ligands on the
      interaction between MSC and natural killer (NK) cells. Our results show that TLR
      primed adult bone marrow and embryonic MSC are more resistant than unprimed MSC
      to IL-2-activated NK-induced killing. Such protection can be explained by the
      modulation of Natural Killer group 2D ligands major histocompatibility complex
      class I chain A and ULBP3 and DNAM-1 ligands by TLR-primed MSC. These results
      indicate that MSCs are able to adapt their immuno-behavior in an inflammatory
      context, decreasing their susceptibility to NK killing. In addition, TLR3 but not
      TLR4-primed MSC enhance their suppressive functions against NK cells. However,
      the efficiency of this response is heterogeneous, even if the phenotypes of
      different analyzed MSC are rather homogeneous. The consequences could be
      important in MSC-mediated cell therapy, since the heterogeneity of adult MSC
      responders may be explored in order to select the more efficient responders.

PMID- 24123640
TI  - Quantitative determination of poly(amidoamine) dendrimers in urine by liquid
      chromatography/electrospray ionization hybrid quadrupole linear ion trap mass
      spectrometry.
AB  - RATIONALE: Dendrimer nanocarriers have become of increasing interest in the field
      of biomedicine for their drug delivery potential. Surface modifications and
      optimized nanosize control are the strategies being followed to enhance drug
      delivery efficacy and renal clearance, especially for dendrimers of a lower
      generation number. The aim of this study was the development and performance
      evaluation of an analytical method for the quantitative determination of
      polyamidoamine (PAMAM) dendrimers in urine. METHODS: PAMAM dendrimers
      (generations G0 to G3) were analyzed using liquid chromatography/electrospray
      ionization hybrid quadrupole linear ion trap mass spectrometry (LC/ESI-QqLIT-MS).
      Quantitative analysis was performed in selected reaction monitoring (SRM) mode.
      To confer a higher degree of confidence on the identification of PAMAM
      dendrimers, an SRM scan and collision-induced dissociation (CID), as a dependent
      scan, were performed in one single run using the information-dependent
      acquisition (IDA) mode. RESULTS: The LC/ESI-QqLIT-MS method, in SRM mode, allowed
      quantitative determination in urine matrix with good repeatability and
      reproducibility (relative standard deviation (R.S.D.) from 2 to 15%), linearity
      (R >0.99) over the concentration range (6?10-4 to 5?10-2  mmol.L-1 ), and
      sensitivity within the micromolar range. The detection limit values were above
      1?10-4  mmol.L-1 in both solvent and urine, for the generations studied.
      CONCLUSIONS: The developed method has demonstrated a capability for the
      identification and quantification of PAMAM dendrimer nanoparticles in a complex
      liquid matrix. The use of an LC/ESI-QqLIT-MS system, of modest m/z range and unit
      resolution, offers an alternative in the analysis of lower generation PAMAM
      dendrimers between mass analyzers of higher resolution and the conventional LC-UV
      method that is commonly applied for dendrimer quantification, but which lacks
      sufficient identification capacity. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123641
TI  - Comparative study of sialyl glycoprotein with multiple glycosylation sites using
      isotope labeling and capillary liquid chromatography/mass spectrometry.
AB  - RATIONALE: A comparative strategy has been demonstrated using RNase B, a single
      site N-linked high-mannose glycoprotein. Glycoproteins are more common with
      multiple glycosylation sites and with complex glycans. A strategy capable of
      differentiating the changes caused by glycoprotein concentration, glycosylation
      site occupancy, and a glycoform profile of complex glycoproteins would be
      beneficial. METHODS: Tryptic-digested glycoproteins were labeled using 12 C,H
      formaldehyde and 13 C, D-formaldehyde, purified, and then analyzed using
      capillary reversed-phase liquid chromatography/mass spectrometry (RPLC/MS). The
      relative intensity of non-glycosylated peptides provided information on
      glycoprotein concentration variation. A site-specific glycoform profile variation
      was obtained by comparing the glycoform profile of CH2 and 13 CD2 glycopeptides.
      Determining the protein concentration and glycoform profile variations allows the
      glycosylation site occupancy variation to be calculated. RESULTS: A strong
      correlation between the observed and prepared ratios for fetuin glycopeptides
      from 0.2 to 5 was obtained. Two fetuin samples with different glycoprotein
      concentrations (4-fold change), glycoform profiles (normal and modified), and
      glycosylation site occupancies (100% and 50%) were prepared, labeled, mixed,
      purified, and analyzed using RPLC/MS. The results of the comparative study had a
      strong correlation with the prepared values. CONCLUSIONS: In this report, we
      demonstrated a comparative analysis of fetuin, a glycoprotein with multiple
      glycosylation sites and complex sialyl glycans. Compared to our previous
      approach, we made several modifications including the use of RPLC, a larger mass
      difference isotope tag, and isotope overlapping correction. The modified approach
      is expected to be applicable to most glycoproteins. Copyright (c) 2013 John Wiley
      & Sons, Ltd.

PMID- 24123642
TI  - Phosphorus and sulfur metabonomic profiling of tissue and plasma obtained from
      tumour-bearing mice using ultra-performance liquid chromatography/inductively
      coupled plasma mass spectrometry.
AB  - RATIONALE: Metabonomic studies use complex biological samples (blood
      plasma/serum, tissues, etc.) that when analysed with high-performance liquid
      chromatography/mass spectrometry (HPLC/MS) or nuclear magnetic resonance (NMR)
      generate profiles that may contain many thousands of features. These profiles can
      be difficult to interpret with the majority of the features contributing little
      to the study. As such there is an argument for the development of techniques that
      can simplify the problem by targeting particular classes of compounds. METHODS:
      In this study ultra-performance liquid chromatography/inductively coupled plasma
      mass spectrometry (UPLC/ICP-MS) was used to profile tumour tissue and plasma
      samples for phosphorus- and sulfur-containing metabolites. These samples were
      xenograft tumours (derived from breast, lung and colon cell lines) and plasma
      obtained from nude mice. Plasma was also obtained from non-tumour-bearing mice as
      a control. Due to isobaric interferences this method took advantage of the
      dynamic reaction cell within the ICP-MS system to react the phosphorus and sulfur
      ions with oxygen. The PO+ and SO+ ions were then monitored free of interferences.
      The total phosphorus and sulfur within each sample was also recorded using flow
      injection ICP-MS. A robust quality control system based on pooled sample
      replicate analysis was used throughout the study. RESULTS: Determination of the
      total phosphorus and sulfur content of each sample was sufficient in itself for
      statistical differentiation between the majority of the cell lines analysed.
      Subsequent reversed-phase chromatographic profiling of the organic tumour and
      plasma extracts revealed the presence of a number of well-retained phosphorus
      containing compounds that showed tumour-specific profiles. Reversed-phase
      profiling was not suitable for the sulfur-containing compounds which eluted with
      the solvent front. CONCLUSIONS: This study has shown the potential use of
      UPLC/ICP-MS to differentiate between tumour cell lines, using both plasma and
      tumour tissue samples, based solely on metabolites that contain phosphorus or
      sulfur. Whilst further work is required to identify these compounds this
      methodology shows the ability of the described methods to provide targets for
      future biomarker discovery studies. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123643
TI  - Compound-specific delta13 C analysis of monosaccharides from soil extracts by
      high-performance liquid chromatography/isotope ratio mass spectrometry.
AB  - RATIONALE: Carbohydrates represent up to 25% of soil organic matter and derive
      from fresh plant input or organic matter transformation within the soil. Compound
      specific isotope analysis (CSIA) of monosaccharides (sugars) extracted from soil
      provides a powerful tool to disentangle the dynamics of different carbohydrate
      pools of soils. The use of high-performance liquid
      chromatography/oxidation/isotope ratio mass spectrometry (HPLC/o/IRMS) allows
      isotope measurements without the need for derivatisation and thus increasing
      accuracy and precision of the isotopic measurement, compared with gas
      chromatography/combustion/isotope ratio mass spectrometry (GC/c/IRMS). METHODS:
      The CSIA of soil carbohydrates was performed using a HPLC/o/IRMS system. The
      chromatographic and mass spectrometric subunits were coupled with a LC-Isolink
      interface. Soil sugars were extracted after mild hydrolysis using 4 M
      trifluoroacetic acid (TFA). Chromatographic separation of the sugars was achieved
      using a low strength 0.25 mM NaOH solution as mobile phase at a flow rate of 250
      MUL min-1 at 10  degrees C. RESULTS: The chromatographic conditions allowed the
      baseline separation of the seven most abundant sugars in soil. Complete removal
      of TFA from the soil hydrolysate ensured chromatographic stability. The accuracy
      was better than 0.66 0/00 for amounts of >2.5 nM sugar on column. The sugars
      extracted from an agricultural soil appeared to be more enriched in 13 C than the
      soil organic carbon, and to have a similar isotopic signature to the soil
      microbial biomass. CONCLUSIONS: The proposed method proved to be suitable for the
      analysis of the common sugars in soil extracts and represents a precise tool for
      the study of carbohydrate dynamics. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123644
TI  - Gas chromatography/mass spectrometry analysis of the six-ring regioisomeric
      dimethoxybenzyl-N-methylpiperazines (DMBMPs).
AB  - RATIONALE: Piperazine-based designer drugs represent a novel class of substances
      found in illicit drug samples in the US and abroad. The clandestine production of
      these substances often makes use of piperazine as a key commercially available
      precursor substance. The commercial availability of 1-methylpiperazine suggests
      additional designer modification based on this additional precursor material.
      METHODS: This study focuses on the electron ionization mass spectrometric (EI-MS)
      fragmentation of the dimethoxybenzyl-N-methylpiperazines as potential designer
      modifications of the general benzylpiperazine drug skeleton and explores the gas
      chromatography (GC)/MS properties of all six of these regioisomeric substances.
      RESULTS: Fragmentation of the bond between the benzylic carbon and the adjacent
      piperazine nitrogen provides the base peak in all six spectra. The internal
      fragmentation within the piperazine ring produces a number of unique ions in the
      mass spectra of these dimethoxybenzyl-N-methylpiperazines. The migration of
      methyl groups from nitrogen and oxygen were confirmed by deuterium-labeling
      experiments. CONCLUSIONS: The six regioisomeric dimethoxybenzyl-N
      methylpiperazines yield equivalent fragment ions and deuterium labeling confirmed
      the elemental composition of the characteristic fragments in their mass spectra.
      Mixtures of the dimethoxybenzyl-N-methylpiperazines were successfully resolved
      via capillary gas chromatography using a relatively polar stationary phase and
      temperature-programming conditions. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123645
TI  - Fourier transform ion cyclotron resonance mass spectrometric analysis of the
      green fraction of soil humic acids.
AB  - RATIONALE: The green fraction of soil humic acids (HAs), designated Pg, contains
      4,9-dihydroxyperylene-3,10-quinone (DHPQ) as a chromophore. Although various
      naturally occurring DHPQ derivatives are known to occur and Pg-like absorption is
      observed in the UV-visible spectra of HAs from various types of soils worldwide,
      the chemical structure of Pg is still unknown. METHODS: For a better
      understanding of the chemical composition of Pg, the pre-isolated (crude Pg) and
      purified Pg (G2) samples and three soil HAs with different degrees of
      humification were analyzed using negative-mode electrospray ionization coupled
      with Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) at 12
      Tesla. The Pg samples were characterized using H/C-O/C ratios and based on the
      type and magnitude of the molecular formulae having DHPQ or related compounds as
      a potential structure. RESULTS: The H/C-O/C diagram indicated that most of the
      lipids, proteins, other aliphatics, and lignin-like components were removed,
      while condensed aromatic components were concentrated during the purification
      process of crude Pg to G2 using Sephadex G-50. More than 27 molecular formulae
      resembling DHPQ, DHPQ substituted with varying numbers of carboxyl and/or
      hydroxyl groups, and phenyl-DHPQ derivatives were identified in both Pg samples.
      The peak magnitudes of these formulae in G2 (accounting for 40% of the total
      assigned magnitude) were greater than that in the crude Pg (21%). Most of the 27
      molecular formulae were also detected in the three soil HAs, suggesting a common
      existence of Pg-related compounds in various soil HAs. CONCLUSIONS: The important
      molecular formulae of Pg components were estimated utilizing FTICRMS. Copyright
      (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123646
TI  - Recognizing the potential pitfalls of hydrogen isotopic analysis of keratins with
      steam equilibration to infer origins of wildlife, food, and people.

PMID- 24123647
TI  - 7th International Symposium on Enabling Technologies for Life Sciences (ETP).

PMID- 24123649
TI  - Effects of increasing CREB-dependent transcription on the storage and recall
      processes in a hippocampal CA1 microcircuit.
AB  - The involvement of the hippocampus in learning processes and major brain diseases
      makes it an ideal candidate to investigate possible ways to devise effective
      therapies for memory-related pathologies like Alzheimer's Disease (AD). It has
      been previously reported that augmenting CREB activity increases the synaptic
      Long-Term Potentiation (LTP) magnitude in CA1 pyramidal neurons and their
      intrinsic excitability in healthy rodents. It has also been suggested that
      hippocampal CREB signaling is likely to be down-regulated during AD, possibly
      degrading memory functions. Therefore, the concept of CREB-based memory
      enhancers, i.e. drugs that would boost memory by activation of CREB, has emerged.
      Here, using a model of a CA1 microcircuit, we investigate whether hippocampal CA1
      pyramidal neuron properties altered by increasing CREB activity may contribute to
      improve memory storage and recall. With a set of patterns presented to a network,
      we find that the pattern recall quality under AD-like conditions is significantly
      better when boosting CREB function with respect to control. The results are
      robust and consistent upon increasing the synaptic damage expected by AD
      progression, supporting the idea that the use of CREB-based therapies could
      provide a new approach to treat AD.

PMID- 24123648
TI  - Corticotropin releasing hormone receptor 2 (CRHR-2) gene is associated with
      decreased risk and severity of posttraumatic stress disorder in women.
AB  - BACKGROUND: The corticotropin releasing hormone (CRH) system has been implicated
      in a variety of anxiety and mood-based symptoms and disorders. CRH receptor-2
      (CRHR-2) plays a role in attenuating biological responses to stressful life
      events and trauma, making the CRHR-2 gene a strong candidate to study in
      relationship to PTSD. METHODS: The sample was 491 trauma-exposed white non
      Hispanic veterans and their cohabitating intimate partners assessed via
      structured interview for lifetime DSM-IV PTSD; just over 60% met criteria for the
      disorder. Thirty-one single nucleotide polymorphisms (SNPs) in and near CRHR-2,
      obtained from an array of 2.5 million markers, were tested for association with
      PTSD diagnosis and symptom severity in the whole sample and in men and women
      separately. RESULTS: Ten SNPs showed nominally significant evidence of
      association with PTSD in the full sample and two SNPs (rs8192496 and rs2190242)
      were significant after permutation-based multiple testing correction (uncorrected
      ps = .0004 and .0005, odds ratios = .60 and .58, respectively). Analyses
      stratified by sex revealed that the effect was specific to women, who comprised
      35% of the sample (uncorrected ps = .0003 and .0002, odds ratios = .41 and .35,
      respectively). Two additional SNPs (rs2267715 and rs2284218) also showed
      significant association with PTSD in women (both uncorrected ps = .001, both odds
      ratios = .48). CONCLUSIONS: Results suggest that CRHR-2 variants may affect risk
      for PTSD in women by attenuating the stress response and reducing symptoms of the
      disorder.

PMID- 24123651
TI  - Creating technological boundaries to protect bedtime: examining work-home
      boundary management, psychological detachment and sleep.
AB  - This study examined the mechanism by which information and communication
      technology (ICT) use at home for work purposes may affect sleep. In this
      investigation, data from 315 employees were used to examine the indirect effect
      of ICT use at home on sleep outcomes through psychological detachment, and how
      boundary creation may moderate this effect. Results revealed the indirect effect
      of increased work-home boundary crossing on sleep (quantity, quality and
      consistency) through psychological detachment occurred only among individuals
      with low boundaries around ICT use and not among those with high boundaries.
      These results suggest that creating boundaries around work-relevant ICT use while
      at home is beneficial to sleep as a recovery process through being able to
      psychologically disengage from work.

PMID- 24123650
TI  - PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis.
AB  - Caveolae are specialized plasma membrane subdomains implicated in cellular
      functions such as migration, signalling and trafficking. Caveolin-1 and
      polymerase I and transcript release factor (PTRF)/cavin-1 are essential for
      caveola formation. Caveolin-1 is overexpressed and secreted in prostate tumors
      and promotes aggressiveness and angiogenesis. In contrast, a lack of PTRF
      expression is reported in prostate cancer, and ectopic PTRF expression in
      prostate cancer cells inhibits tumor growth and metastasis. We experimentally
      manipulated PTRF expression in three prostate cancer cell lines, namely the
      caveolin-1 positive cells PC3 and DU145 and the caveolin-1-negative LNCaP cells,
      to evaluate angiogenesis- and lymphangiogenesis-regulating functions of PTRF. We
      show that the conditioned medium of PTRF-expressing prostate cancer cells
      decreases ECs proliferation, migration and differentiation in vitro and ex vivo.
      This can occur independently from caveolin-1 expression and secretion or caveola
      formation, since the anti-angiogenic effects of PTRF were detected in caveolin-1
      negative LNCaP cells. Additionally, PTRF expression in PC3 cells significantly
      decreased blood and lymphatic vessel densities in orthotopic tumors in mice. Our
      results suggest that the absence of PTRF in prostate cancer cells contributes
      significantly to tumour progression and metastasis by promoting the angiogenesis
      and lymphangiogenesis potential of the cancer cells, and this could be exploited
      for therapy. 

PMID- 24123652
TI  - The Haber-Bosch process revisited: on the real structure and stability of
      "ammonia iron" under working conditions.

PMID- 24123653
TI  - The effect of Medicaid policies on the diagnosis and treatment of children's
      mental health problems in primary care.
AB  - Primary care physicians play a substantial role in diagnosing and treating
      children's mental health disorders, but Medicaid managed care policies may limit
      these physicians' ability to serve low-income children. Using data from the
      universe of Medicaid recipients in three states, I evaluate how Medicaid managed
      care policies impact primary care diagnosis and treatment of children's mental
      health disorders. Specific policies examined include the presence of a behavioral
      carve-out, traditional health maintenance organization, or primary care case
      management program. To alleviate concerns of endogenous patient sorting, my
      preferred identification strategy uses variation in Medicaid policy penetration
      to instrument for individual plan choices. I show that while health maintenance
      organizations reduce diagnosis and non-drug treatment of mental health disorders,
      primary care case management program policies shift in diagnosis and treatment
      from within primary care to specialist providers such as psychiatrists, where
      serious mental health conditions are more likely to be identified.

PMID- 24123654
TI  - Application of H/D exchange to hydrogen bonding in small molecules.

PMID- 24123655
TI  - Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic
      steatosis.
AB  - PURPOSE: To compare the accuracy of liver fat quantification using a three-echo
      chemical shift-encoded magnetic resonance imaging (MRI) technique without and
      with correction for confounders with spectroscopy (MRS) as the reference
      standard. MATERIALS AND METHODS: Fifty patients (23 women, mean age 56.6 +/- 13.2
      years) with fatty liver disease were enrolled. Patients underwent T2-corrected
      single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE)
      sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and
      T1 correction and multispectral modeling of fat and compared with MRS-FF using
      linear regression. RESULTS: The spectroscopic range of liver fat was 0.11%-38.7%.
      Excellent correlation between MRS-FF and MRI-FF was observed when using T2*
      correction (R(2)  = 0.96). With use of T2* correction alone, the slope was
      significantly different from 1 (1.16 +/- 0.03, P < 0.001) and the intercept was
      different from 0 (1.14% +/- 0.50%, P < 0.023). This slope was significantly
      different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and
      spectral complexity of fat were addressed, the results showed equivalence between
      fat quantification using MRI and MRS (slope: 1.02 +/- 0.03, P = 0.528; intercept:
      0.26% +/- 0.46%, P = 0.572). CONCLUSION: Complex three-echo chemical shift
      encoded MRI is equivalent to MRS for quantifying liver fat, but only with
      correction for T2* decay and T1 recovery and use of spectral modeling of fat.
      This is necessary because T2* decay, T1 recovery, and multispectral complexity of
      fat are processes which may otherwise bias the measurements.

PMID- 24123657
TI  - Comparison of complications in free flap reconstruction for osteoradionecrosis in
      patients with or without hyperbaric oxygen therapy.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) therapy induces native tissue oxygenation.
      The hypothesis was patients with mandibular osteoradionecrosis (ORN) and a
      history of HBO therapy would have less free flap reconstruction complications
      than patients without HBO therapy. METHODS: We conducted a multisite
      retrospective review involving radical debridement and free flap reconstruction
      for ORN between January 1, 1995 and June 30, 2011. Patients were stratified based
      on receiving prior HBO therapy or not. RESULTS: Thirty-nine of 89 patients
      (43.8%) had HBO therapy whereas 50 of 89 (56.2%) did not. The HBO therapy group
      had significantly less patients with diabetes. There was no statistical
      difference in overall complication in patients between groups (p = .5478).
      However, there was marginal significance of increased infections in the patients
      with a history of HBO therapy (p = .0545). CONCLUSION: Although no significant
      differences in free flap reconstruction complication rates were observed between
      these 2 patient cohorts, there was marginal significance of increased infections
      in the patients with a history of HBO therapy. A prospective multi-institutional
      randomized study examining issues of infection would address issues inherent in
      this retrospective study.

PMID- 24123658
TI  - BMP growth factor signaling in a biomechanical context.
AB  - Bone Morphogenetic Proteins (BMPs) are members of the transforming growth factor
      beta superfamily of secreted polypeptide growth factors and are important
      regulators in a multitude of cellular processes. To ensure the precise and
      balanced propagation of their pleiotropic signaling responses, BMPs and their
      corresponding signaling pathways are subject to tight control. A large variety of
      regulatory mechanisms throughout different biological levels combines into a
      complex network and provides the basis for physiological BMP function. This
      regulatory network not only includes biochemical factors but also mechanical
      cues. Both BMP signaling and mechanotransduction pathways are tightly
      interconnected and represent an elaborate signaling network active during
      development but also during organ homeostasis. Moreover, its dysregulation is
      associated with a number of human pathologies. A more detailed understanding of
      this crosstalk in respect to molecular interactions will be indispensable in the
      future, in particular to understand BMP-related diseases as well as with regard
      to an efficient clinical application of BMP ligands.

PMID- 24123659
TI  - Alternating asymmetric self-induction in functionalized pyrrolidine oligomers.

PMID- 24123660
TI  - Highly enantioselective bromocyclization of tryptamines and its application in
      the synthesis of (-)-chimonanthine.
AB  - A shorter path: A highly enantioselective bromocyclization of tryptamine has been
      developed using an anionic chiral phase-transfer catalyst. This method provides a
      direct approach for preparing chiral 3-bromopyrroloindoline from tryptamine,
      which enables a four-step enantioselective synthesis of (-)-chimonanthine.
      PG=protecting group. 

PMID- 24123661
TI  - Visualizing lithium-ion migration pathways in battery materials.
AB  - The understanding of lithium-ion migration through the bulk crystal structure is
      crucial in the search for novel battery materials with improved properties for
      lithium-ion conduction. In this paper, procrystal calculations are introduced as
      a fast, intuitive way of mapping possible migration pathways, and the method is
      applied to a broad range of lithium-containing materials, including the well
      known battery cathode materials LiCoO2 , LiMn2 O4 , and LiFePO4 . The outcome is
      compared with both experimental and theoretical studies, as well as the bond
      valence site energy approach, and the results show that the method is not only a
      strong, qualitative visualization tool, but also provides a quantitative measure
      of electron-density thresholds for migration, which are correlated with
      theoretically obtained activation energies. In the future, the method may be used
      to guide experimental and theoretical research towards materials with potentially
      high ionic conductivity, reducing the time spent investigating nonpromising
      materials with advanced theoretical methods. 

PMID- 24123662
TI  - Nuclear Akt2 opposes limbal keratinocyte stem cell self-renewal by repressing a
      FOXO-mTORC1 signaling pathway.
AB  - Signals downstream of Akt can either favor or oppose stem cell (SC) maintenance,
      but how this dual role can be achieved is still undefined. Using human limbal
      keratinocyte stem cells (LKSCs), a SC type used in transplantation therapies for
      corneal regeneration, we show that Akt signaling is prominent in SC populations
      both in vivo and in vitro, and that Akt1 promotes while Akt2 opposes SC self
      renewal. Noteworthy, loss of Akt2 signaling enhances LKSC maintenance ex vivo,
      whereas Akt1 depletion anticipates SC exhaustion. Mechanistically, the
      antagonistic functions of Akt1 and Akt2 in SC control are mainly dictated by
      their differential subcellular distribution, being nuclear Akt2 selectively
      implicated in FOXO inhibition. Akt2 downregulation favors LKSC maintenance as a
      result of a gain of FOXO functions, which attenuates the mechanistic target of
      rapamycin complex one signaling via tuberous sclerosis one gene induction, and
      promotes growth factor signaling through Akt1. Consistently, Akt2 deficiency also
      enhances limbal SCs in vivo. Thus, our findings reveal distinct roles for nuclear
      versus cytosolic Akt signaling in normal epithelial SC control and suggest that
      the selective Akt2 inhibition may provide novel pharmacological strategies for
      human LKSC expansion in therapeutic settings and mechanistic research.

PMID- 24123663
TI  - Correction of B0-distortions in echo-planar-imaging-based perfusion-weighted MRI.
AB  - PURPOSE: To evaluate and quantify a scheme for correcting susceptibility
      artifacts in spin-echo echo-planar-imaging-based dynamic susceptibility contrast
      (DSC) perfusion MRI of high-grade gliomas at 3 Tesla. MATERIALS AND METHODS:
      Sixteen patients with a total of 78 scans were studied. DSC-MRI images were
      corrected using a displacement map generated from opposite phase-encoding
      polarity images. Two methods were used for quantification in the correction: (i)
      linear regression of pixel-by-pixel comparisons, performed both globally and
      relative to the anterior and posterior commissure plane (AC-PC plane), of T2
      weighted images with both corrected and uncorrected raw DSC images; and (ii)
      counting significant (>2.0) normalized cerebral blood volume (nCBV) pixels from
      perfusion maps in the tumor region of interest. RESULTS: Sixty-four of 78
      datasets showed significant differences in the coefficient of correlation (r2)
      values. The difference between corrected and uncorrected r2 values was positive
      in all but one patient. Correction of B0- distortion significantly improved r2 in
      slices around the AC-PC plane. In 62% of the datasets, we observed an increased
      number of significant pixels in the corrected nCBV maps; 36% showed more
      significant pixels in uncorrected nCBV maps; 1% showed no difference. CONCLUSION:
      Distortion correction of DSC-MRI may provide improved accuracy compared with
      uncorrected data, especially for tumors located below the corpus callosum and
      near the frontal sinuses.

PMID- 24123664
TI  - Stigma among patients with lung cancer: a patient-reported measurement model.
AB  - BACKGROUND: Although stigma may have negative psychosocial and behavioral
      outcomes for patients with lung cancer, its measurement has been limited. A
      conceptual model of lung cancer stigma and a patient-reported outcome measure are
      needed to mitigate these sequelae. This study identified key stigma-related
      themes to provide a blueprint for item development through a thematic analysis of
      semi-structured interviews and focus groups with lung cancer patients. METHODS:
      Participants were recruited from two outpatient oncology clinics and included (i)
      42 lung cancer patients who participated in individual interviews and (ii) 5
      focus groups (inclusive of 23 new lung cancer patients). Never smokers, long-term
      quitters, recent quitters, and current smokers participated. Individual
      interviews facilitated theme development and a conceptual model of lung cancer
      stigma, whereas subsequent focus groups provided feedback on the conceptual
      model. Qualitative data analyses included iterative coding and validation with
      existing theory. RESULTS: Two main thematic elements emerged from interviews with
      lung cancer patients: perceived (felt) stigma and internalized (self) stigma.
      Discussions of perceived stigma were pervasive, whereas those of internalized
      stigma were more commonly endorsed among current and recently quit smokers.
      Participants also discussed maladaptive (e.g., decreased disclosure) and adaptive
      (e.g., increased advocacy) stigma-related consequences. CONCLUSIONS: Results
      indicate widespread acknowledgment of perceived stigma among lung cancer patients
      but varying degrees of internalized stigma and associated consequences. Next
      steps for patient-reported outcome measure development are item consolidation,
      item development, expert input, and cognitive interviews before field testing and
      psychometric analysis. Future work should address stigma-related consequences and
      interventions for reducing lung cancer stigma.

PMID- 24123665
TI  - Job demands * job control interaction effects: do occupation-specific job demands
      increase their occurrence?
AB  - Despite evidence that the accurate assessment of occupational health should
      include measures of both generic job demands and occupation-specific job demands,
      most research includes only generic job demands. The inclusion of more focused
      occupation-specific job demands is suggested to explain a larger proportion of
      variance for both direct effects and job demands * job control/support
      interaction effects, as compared with the inclusion of generic job demands. This
      research tested these two propositions via a self-report survey assessing key
      psychological job characteristics administered twice to a sample of correctional
      workers (N = 746). The research clearly identified that the assessment of
      correctional-specific job demands (CJD) was more strongly associated with job
      satisfaction, work engagement, turnover intentions and psychological strain, as
      compared with an assessment of generic job demands. However, the CJD did not
      produce a greater proportion of significant job demands * job control/support
      interaction effects, as compared with the generic job demands measure. The
      results thereby provide further support for the acknowledged 'elusiveness' of
      these theoretical interactions. Overall, however, the results did support the
      inclusion of occupation-specific measures of job demands for the accurate
      assessment of the health and job performance of high-risk workers. The
      implications for theoretical discussions that describe how high job demands are
      moderated by job resources are discussed.

PMID- 24123666
TI  - Switchable pickering emulsions stabilized by silica nanoparticles hydrophobized
      in situ with a switchable surfactant.
AB  - Back and forth: The CO2 /N2 trigger of a switchable surfactant (neutral
      amidine/cationic amidinium) was transferred to mineral nanoparticles through in
      situ hydrophobization in water. Switchable oil-in-water Pickering emulsions that
      entail a CO2 /N2 trigger were obtained by using negatively charged silica
      nanoparticles and a trace amount of the switchable surfactant as the stabilizer. 

PMID- 24123667
TI  - CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and
      memory deficits following treatment with JWH-081, a new component of spice/K2
      preparations.
AB  - Recently, synthetic cannabinoids have been sprayed onto plant material, which is
      subsequently packaged and sold as "Spice" or "K2" to mimic the effects of
      marijuana. A recent report identified several synthetic additives in samples of
      "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1
      (CB1). The deleterious effects of JWH-081 on brain function are not known,
      particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we
      evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events
      followed by long-term potentiation (LTP), hippocampal-dependent learning and
      memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute
      administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent
      manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was
      observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose
      impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1
      receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation.
      In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio
      and higher pCREB/CREB ratio compared with vehicle or WT littermates. In
      hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO
      littermates. Furthermore, JWH-081 at higher dose impaired object recognition,
      spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice
      but not in KO mice. Collectively our findings suggest that deleterious effects of
      JWH-081 on hippocampal function involves CB1 receptor mediated impairments in
      CaMKIV and CREB phosphorylation, LTP, learning and memory in mice.

PMID- 24123669
TI  - Comparison of different methods for the isolation of mesenchymal stem cells from
      umbilical cord matrix: proliferation and multilineage differentiation as compared
      to mesenchymal stem cells from umbilical cord blood and bone marrow.
AB  - We have identified the most appropriate method of isolating human umbilical cord
      matrix-derived mesenchymal stem cells (UCM-MSCs) and compared morphological,
      phenotypic, proliferative, and differentiation characteristics of UCM-MSCs with
      bone marrow-derived MSCs (BM-MSCs) and umbilical cord blood-derived MSCs (UCB
      MSCs). Three explant culture methods and 3 enzymatic methods were compared with
      regards to time for primary culture, cell number, cell morphology, immune
      phenotype, and differentiation potential. Morphological, phenotypic,
      proliferative, and differentiation characteristics of UCM-MSCs, BM-MSCs, and UCB
      MSCs were also compared. UCM-MSCs isolated using the 10 mm size tissue explant
      method led to shorter primary culture time, higher numbers of isolated cells, and
      higher proliferation rates compared with other isolation methods. Immune
      phenotype and multilineage differentiation capacity did not differ significantly
      among 6 groups. UCM-MSCs had similar characteristics as BM-MSCs and UCB-MSCs,
      including fibroblastic morphology, typical immunophenotypic markers, and
      multilineage differentiation capacity. In comparison with UCB-MSCs and BM-MSCs,
      UCM-MSCs have higher proliferative capacity, higher rate of chondrogenic
      differentiation, and higher expression of CD 146. The results suggest that the 10
      mm size tissue culture method is the optimal protocol for the isolation of UCM
      MSCs. Given the distinct advantages of UC, such as accessibility, painless
      acquisition, and abundance of cells obtained, we propose that UC be considered an
      alternative to BM and UCB as a source of MSCs for cell therapy.

PMID- 24123668
TI  - Neighborhood characteristics and differential risk for depressive and anxiety
      disorders across racial/ethnic groups in the United States.
AB  - BACKGROUND: The prevalence of psychiatric disorders varies depending on the
      person's neighborhood context, their racial/ethnic group, and the specific
      diagnoses being examined. Less is known about specific neighborhood features that
      represent differential risk for depressive and anxiety disorders (DAD) across
      racial/ethnic groups in the United States. This study examines whether
      neighborhood etiologic factors are associated with DAD, above and beyond
      individual-level characteristics, and whether these associations are moderated by
      race/ethnicity. METHODS: We utilized nationally representative data (N = 13,837)
      from the Collaborative Psychiatric Epidemiology Studies (CPES-Geocode file).
      Separate weighted multilevel logistic regression models were fitted for any past
      year depressive and/or anxiety disorder, any depressive disorder only, and any
      anxiety disorder only. RESULTS: After adjusting for individual-level
      characteristics, African Americans living in a neighborhood with greater
      affluence and Afro-Caribbeans residing in more residentially unstable
      neighborhoods were at increased risk for any past-year depressive disorder as
      compared to their non-Latino white counterparts. Further, Latinos residing in
      neighborhoods with greater levels of Latino/immigrant concentration were at
      increased risk of any past-year anxiety disorder. Lastly, Asians living in
      neighborhoods with higher levels of economic disadvantage were at decreased risk
      of any past-year depressive and/or anxiety disorders compared to non-Latino
      whites, independent of individual-level factors. Differences across subethnic
      groups are also evident. CONCLUSIONS: Results suggest neighborhood
      characteristics operate differently on risk for DAD across racial/ethnic groups.
      Our findings have important implications for designing and targeting
      interventions to address DAD risk among racial/ethnic minorities.

PMID- 24123670
TI  - Thrombolytic therapy using a low dose of tissue plasminogen activator in
      children.

PMID- 24123671
TI  - SOAPfusion: a robust and effective computational fusion discovery tool for RNA
      seq reads.
AB  - MOTIVATION: RNA-Seq provides a powerful approach to carry out ab initio
      investigation of fusion transcripts representing critical translocation and post
      transcriptional events that recode hereditary information. Most of the existing
      computational fusion detection tools are challenged by the issues of accuracy and
      how to handle multiple mappings. RESULTS: We present a novel tool SOAPfusion for
      fusion discovery with paired-end RNA-Seq reads. SOAPfusion is accurate and
      efficient for fusion discovery with high sensitivity (>=93%), low false-positive
      rate (<=1.36%), even the coverage is as low as 10*, highlighting its ability to
      detect fusions efficiently at low sequencing cost. From real data of Universal
      Human Reference RNA (UHRR) samples, SOAPfusion detected 7 novel fusion genes,
      more than other existing tools and all genes have been validated through reverse
      transcription-polymerase chain reaction followed by Sanger sequencing. SOAPfusion
      thus proves to be an effective method with precise applicability in search of
      fusion transcripts, which is advantageous to accelerate pathological and
      therapeutic cancer studies.

PMID- 24123672
TI  - Nonpareil: a redundancy-based approach to assess the level of coverage in
      metagenomic datasets.
AB  - MOTIVATION: Determining the fraction of the diversity within a microbial
      community sampled and the amount of sequencing required to cover the total
      diversity represent challenging issues for metagenomics studies. Owing to these
      limitations, central ecological questions with respect to the global distribution
      of microbes and the functional diversity of their communities cannot be robustly
      assessed. RESULTS: We introduce Nonpareil, a method to estimate and project
      coverage in metagenomes. Nonpareil does not rely on high-quality assemblies,
      operational taxonomic unit calling or comprehensive reference databases; thus, it
      is broadly applicable to metagenomic studies. Application of Nonpareil on
      available metagenomic datasets provided estimates on the relative complexity of
      soil, freshwater and human microbiome communities, and suggested that ~200 Gb of
      sequencing data are required for 95% abundance-weighted average coverage of the
      soil communities analyzed. AVAILABILITY AND IMPLEMENTATION: Nonpareil is
      available at https://github.com/lmrodriguezr/nonpareil/ under the Artistic
      License 2.0.

PMID- 24123673
TI  - Two novel pathway analysis methods based on a hierarchical model.
AB  - MOTIVATION: Over the past few years several pathway analysis methods have been
      proposed for exploring and enhancing the analysis of genome-wide association
      data. Hierarchical models have been advocated as a way to integrate SNP and
      pathway effects in the same model, but their computational complexity has
      prevented them being applied on a genome-wide scale to date. METHODS: We present
      two novel methods for identifying associated pathways. In the proposed
      hierarchical model, the SNP effects are analytically integrated out of the
      analysis, allowing computationally tractable model fitting to genome-wide data.
      The first method uses Bayes factors for calculating the effect of the pathways,
      whereas the second method uses a machine learning algorithm and adaptive lasso
      for finding a sparse solution of associated pathways. RESULTS: The performance of
      the proposed methods was explored on both simulated and real data. The results of
      the simulation study showed that the methods outperformed some well-established
      association methods: the commonly used Fisher's method for combining P-values and
      also the recently published BGSA. The methods were applied to two genome-wide
      association study datasets that aimed to find the genetic structure of platelet
      function and body mass index, respectively. The results of the analyses
      replicated the results of previously published pathway analysis of these
      phenotypes but also identified novel pathways that are potentially involved.
      AVAILABILITY: An R package is under preparation. In the meantime, the scripts of
      the methods are available on request from the authors.

PMID- 24123674
TI  - PLIDA: cross-platform gene expression normalization using perturbed topic models.
AB  - MOTIVATION: Gene expression data are currently collected on a wide range of
      platforms. Differences between platforms make it challenging to combine and
      compare data collected on different platforms. We propose a new method of cross
      platform normalization that uses topic models to summarize the expression
      patterns in each dataset before normalizing the topics learned from each dataset
      using per-gene multiplicative weights. RESULTS: This method allows for cross
      platform normalization even when samples profiled on different platforms have
      systematic differences, allows the simultaneous normalization of data from an
      arbitrary number of platforms and, after suitable training, allows for online
      normalization of expression data collected individually or in small batches. In
      addition, our method outperforms existing state-of-the-art platform normalization
      tools. AVAILABILITY AND IMPLEMENTATION: MATLAB code is available at
      http://morrislab.med.utoronto.ca/plida/.

PMID- 24123675
TI  - GIIRA--RNA-Seq driven gene finding incorporating ambiguous reads.
AB  - MOTIVATION: The reliable identification of genes is a major challenge in genome
      research, as further analysis depends on the correctness of this initial step.
      With high-throughput RNA-Seq data reflecting currently expressed genes, a
      particularly meaningful source of information has become commonly available for
      gene finding. However, practical application in automated gene identification is
      still not the standard case. A particular challenge in including RNA-Seq data is
      the difficult handling of ambiguously mapped reads. RESULTS: We present GIIRA
      (Gene Identification Incorporating RNA-Seq data and Ambiguous reads), a novel
      prokaryotic and eukaryotic gene finder that is exclusively based on a RNA-Seq
      mapping and inherently includes ambiguously mapped reads. GIIRA extracts
      candidate regions supported by a sufficient number of mappings and reassigns
      ambiguous reads to their most likely origin using a maximum-flow approach. This
      avoids the exclusion of genes that are predominantly supported by ambiguous
      mappings. Evaluation on simulated and real data and comparison with existing
      methods incorporating RNA-Seq information highlight the accuracy of GIIRA in
      identifying the expressed genes. AVAILABILITY AND IMPLEMENTATION: GIIRA is
      implemented in Java and is available from
      https://sourceforge.net/projects/giira/.

PMID- 24123676
TI  - Identification of a novel fusion gene involving RUNX1 and the antisense strand of
      SV2B in a BCR-ABL1-positive acute leukemia.
AB  - RUNX1, a key regulator of hematopoiesis, is frequently mutated or implicated in
      chromosomal translocations in acute leukemia. About half of RUNX1 translocations
      remain uncharacterized at the molecular level. We describe here one such event, a
      t(15;21)(q26.1;q22) translocation identified in an adult patient diagnosed with a
      t(9;22)(q34;q11.2)-positive acute leukemia. This previously unreported
      rearrangement yields a fusion of RUNX1 with the antisense strand of the SV2B
      gene, a new translocation partner of RUNX1, resulting in the expression of out-of
      frame mRNA chimeric transcripts and the production of putative truncated RUNX1
      isoforms. The t(15;21) translocation also dissociates the P1 promoter of RUNX1
      from its open reading frame, reducing RUNX1 expression levels in the patient's
      leukemic cells. Our data suggest that RUNX1 haploinsufficiency collaborates with
      the BCR-ABL1 oncogene in this leukemia. The description of this atypical gene
      fusion is an important addition to the characterization of the pathogenomic
      mechanisms leading to RUNX1 structural and functional alterations. Furthermore,
      our data strongly suggests that inadequate dosage of this gene plays an essential
      role in leukemogenesis.

PMID- 24123677
TI  - A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine
      arthritis by blocking IL-17 signaling, distinct from methotrexate and
      leflunomide.
AB  - Iguratimod, a novel disease-modifying antirheumatic drug, which is now used in
      clinics in China and Japan, has been confirmed as a highly efficacious and safe
      drug for rheumatoid arthritis therapy. The antiarthritic mechanism of iguratimod,
      especially compared with that of the classical disease-modifying antirheumatic
      drugs, has not been elucidated. In this study, we conducted a comparative
      analysis of the antiarthritic effects of iguratimod and two reference drugs,
      methotrexate and leflunomide. We found that iguratimod dose dependently and
      potently inhibited arthritic inflammation of the synovium in collagen-induced
      arthritis and predominantly targeted IL-17 signaling. Consistent with its effects
      in vivo, iguratimod significantly suppressed the expression of various
      proinflammatory factors triggered by IL-17 in the cultured fibroblast-like
      synoviocytes. The inhibition of IL-17 signaling by iguratimod was further linked
      to a decrease in the mRNA stability of related genes and a reduction in
      phosphorylation of MAPKs. Iguratimod mainly targets Act1 to disrupt the
      interaction between Act1 and TRAF5 and IKKi in the IL-17 pathway of synoviocytes.
      Together, our results suggest that iguratimod yields a strong improvement in
      arthritis via its unique suppression of IL-17 signaling in fibroblast-like
      synoviocytes. This feature of iguratimod is different from those of methotrexate
      and leflunomide. This study may be helpful for further understanding the unique
      antiarthritic mechanism of iguratimod in patients with rheumatoid arthritis. 

PMID- 24123678
TI  - Targeting F box protein Fbxo3 to control cytokine-driven inflammation.
AB  - Cytokine-driven inflammation underlies the pathobiology of a wide array of
      infectious and immune-related disorders. The TNFR-associated factor (TRAF)
      proteins have a vital role in innate immunity by conveying signals from cell
      surface receptors to elicit transcriptional activation of genes encoding
      proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box
      component, termed Fbxo3, potently stimulates cytokine secretion from human
      inflammatory cells by mediating the degradation of the TRAF inhibitory protein,
      Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial
      like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and
      stimulating cytokine secretion. By targeting this ApaG motif, we developed a
      highly unique, selective genus of small-molecule Fbxo3 inhibitors that by
      reducing TRAF protein levels, potently inhibited cytokine release from human
      blood mononuclear cells. The Fbxo3 inhibitors effectively lessened the severity
      of viral pneumonia, septic shock, colitis, and cytokine-driven inflammation
      systemically in murine models. Thus, pharmacological targeting of Fbxo3 might be
      a promising strategy for immune-related disorders characterized by a heightened
      host inflammatory response. 

PMID- 24123679
TI  - Increased level of E protein activity during invariant NKT development promotes
      differentiation of invariant NKT2 and invariant NKT17 subsets.
AB  - E protein transcription factors and their natural inhibitors, Id proteins, play
      critical and complex roles during lymphoid development. In this article, we
      report that partial maintenance of E protein activity during positive selection
      results in a change in the cell fate determination of developing iNKT cells, with
      a block in the development of iNKT1 cells and a parallel increase in the iNKT2
      and iNKT17 subsets. Because the expression levels of the transcription factors
      that drive these alternative functional fates (GATA-3, RORgammaT, T-bet, and Runx
      3) are not altered, our results suggest that E protein activity controls a novel
      checkpoint that regulates the number of iNKT precursors that choose each fate. 

PMID- 24123680
TI  - Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in
      invariant NKT cell development and expansion.
AB  - The invariant NKT (iNKT) cells represent a unique group of alphabeta T cells that
      have been classified based on their exclusive usage of the invariant
      Valpha14Jalpha18 TCRalpha-chain and their innate-like effector function. Thus
      far, the transcriptional programs that control Valpha14Jalpha18 TCRalpha
      rearrangements and the population size of iNKT cells are still incompletely
      defined. E protein transcription factors have been shown to play necessary roles
      in the development of multiple T cell lineages, including iNKT cells. In this
      study, we examined E protein functions in T cell development through combined
      deletion of genes encoding E protein inhibitors Id2 and Id3. Deletion of Id2 and
      Id3 in T cell progenitors resulted in a partial block at the pre-TCR selection
      checkpoint and a dramatic increase in numbers of iNKT cells. The increase in iNKT
      cells is accompanied with a biased rearrangement involving Valpha14 to Jalpha18
      recombination at the double-positive stage and enhanced proliferation of iNKT
      cells. We further demonstrate that a 50% reduction of E proteins can cause a
      dramatic switch from iNKT to innate-like gammadelta T cell fate in Id2- and Id3
      deficient mice. Collectively, these findings suggest that Id2- and Id3-mediated
      inhibition of E proteins controls iNKT development by restricting lineage choice
      and population expansion. 

PMID- 24123681
TI  - Wnt6 is expressed in granulomatous lesions of Mycobacterium tuberculosis-infected
      mice and is involved in macrophage differentiation and proliferation.
AB  - The Wnt signaling network, an ancient signaling system governing ontogeny and
      homeostatic processes, has recently been identified to exert immunoregulatory
      functions in a variety of inflammatory and infectious disease settings including
      tuberculosis. In this study, we show that Wnt6 is expressed in granulomatous
      lesions in the lung of Mycobacterium tuberculosis-infected mice. We identified
      foamy macrophage-like cells as the primary source of Wnt6 in the infected lung
      and uncovered a TLR-MyD88-NF-kappaB-dependent mode of induction in bone marrow
      derived macrophages. Analysis of Wnt6-induced signal transduction revealed a
      pertussis toxin-sensitive, ERK-mediated, but beta-catenin-independent induction
      of c-Myc, a master regulator of cell proliferation. Increased Ki-67 mRNA
      expression levels and enhanced thymidine incorporation in Wnt6-treated macrophage
      cultures demonstrate a proliferation-promoting effect on murine macrophages.
      Further functional studies in M. tuberculosis-infected macrophages using Wnt6
      conditioned medium and Wnt6-deficient macrophages uncovered a Wnt6-dependent
      induction of macrophage Arginase-1 and downregulation of TNF-alpha. This
      identifies Wnt6 as a novel factor driving macrophage polarization toward an M2
      like phenotype. Taken together, these findings point to an unexpected role for
      Wnt6 in macrophage differentiation in the M. tuberculosis-infected lung. 

PMID- 24123682
TI  - Cutting edge: type 1 diabetes occurs despite robust anergy among endogenous
      insulin-specific CD4 T cells in NOD mice.
AB  - Insulin-specific CD4(+) T cells are required for type 1 diabetes. How these cells
      are regulated and how tolerance breaks down are poorly understood because of a
      lack of reagents. Therefore, we used an enrichment method and tetramer reagents
      to track insulin-specific CD4(+) T cells in diabetes-susceptible NOD and
      resistant B6 mice expressing I-A(g7). Insulin-specific cells were detected in
      both strains, but they only became activated, produced IFN-gamma, and infiltrated
      the pancreas in NOD mice. Unexpectedly, the majority of Ag-experienced cells in
      NOD mice displayed an anergic phenotype, but this population decreased with age
      as tolerance was lost. B6 mice expressing I-A(g7) were protected because insulin
      specific cells did not become effector or anergic T cells but remained naive.
      These data suggest that NOD mice promote tolerance through anergy induction, but
      a small proportion of autoreactive T cells escape anergy to provoke type 1
      diabetes. 

PMID- 24123683
TI  - Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL
      2 in vivo.
AB  - Natural regulatory T cells (nTregs) play an important role in tolerance; however,
      the small numbers of cells obtainable potentially limit the feasibility of
      clinical adoptive transfer. Therefore, we studied the feasibility and efficacy of
      using murine-induced regulatory T cells (iTregs) for the induction of tolerance
      after bone marrow transplantation. iTregs could be induced in large numbers from
      conventional donor CD4 and CD8 T cells within 1 wk and were highly suppressive.
      During graft-versus-host disease (GVHD), CD4 and CD8 iTregs suppressed the
      proliferation of effector T cells and the production of proinflammatory
      cytokines. However, unlike nTregs, both iTreg populations lost Foxp3 expression
      within 3 wk in vivo, reverted to effector T cells, and exacerbated GVHD. The loss
      of Foxp3 in iTregs followed homeostatic and/or alloantigen-driven proliferation
      and was unrelated to GVHD. However, the concurrent administration of rapamycin,
      with or without IL-2/anti-IL-2 Ab complexes, to the transplant recipients
      significantly improved Foxp3 stability in CD4 iTregs (and, to a lesser extent,
      CD8 iTregs), such that they remained detectable 12 wk after transfer. Strikingly,
      CD4, but not CD8, iTregs could then suppress Teff proliferation and
      proinflammatory cytokine production and prevent GVHD in an equivalent fashion to
      nTregs. However, at high numbers and when used as GVHD prophylaxis, Tregs
      potently suppress graft-versus-leukemia effects and so may be most appropriate as
      a therapeutic modality to treat GVHD. These data demonstrate that CD4 iTregs can
      be produced rapidly in large, clinically relevant numbers and, when transferred
      in the presence of systemic rapamycin and IL-2, induce tolerance in transplant
      recipients. 

PMID- 24123684
TI  - Cutting edge: identification of the thymic stromal lymphopoietin-responsive
      dendritic cell subset critical for initiation of type 2 contact hypersensitivity.
AB  - The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the
      initiation and progression of allergic inflammation through its ability to
      activate dendritic cells (DCs). However, the identity of the DC subset that
      responds to TSLP is not known. In this study we use a CCL17 reporter strain to
      identify the TSLP-responsive DC subset. In vitro, TSLP induced CD11b(high) DCs to
      express CCL17, to increase CCR7-mediated migration activity, and to drive Th2
      differentiation of naive CD4 T cells. In vivo, following skin sensitization, we
      found that a subset of Ag-bearing CCL17(+)CD11b(high) migratory DCs, but not Ag
      bearing CCL17(-) migratory DCs, in skin lymph nodes were capable of driving Th2
      differentiation and were dramatically reduced in TSLPR-deficient mice. Taken
      together, these results demonstrate that TSLP activated a subset of CD11b(+) DCs
      in the skin to produce CCL17, upregulate CCR7, and migrate to the draining lymph
      node to initiate Th2 differentiation. 

PMID- 24123685
TI  - Salmonella infection induces recruitment of Caspase-8 to the inflammasome to
      modulate IL-1beta production.
AB  - Nucleotide-binding oligomerization domain-like receptors (NLRs) detect pathogens
      and danger-associated signals within the cell. Salmonella enterica serovar
      Typhimurium, an intracellular pathogen, activates caspase-1 required for the
      processing of the proinflammatory cytokines, pro-IL-1beta and pro-IL-18, and
      pyroptosis. In this study, we show that Salmonella infection induces the
      formation of an apoptosis-associated specklike protein containing a CARD (ASC)
      Caspase-8-Caspase-1 inflammasome in macrophages. Caspase-8 and caspase-1 are
      recruited to the ASC focus independently of one other. Salmonella infection
      initiates caspase-8 proteolysis in a manner dependent on NLRC4 and ASC, but not
      NLRP3, caspase-1 or caspase-11. Caspase-8 primarily mediates the synthesis of pro
      IL-1beta, but is dispensable for Salmonella-induced cell death. Overall, our
      findings highlight that the ASC inflammasome can recruit different members of the
      caspase family to induce distinct effector functions in response to Salmonella
      infection. 

PMID- 24123686
TI  - The role of CD8+ T cells and their local interaction with CD4+ T cells in myelin
      oligodendrocyte glycoprotein35-55-induced experimental autoimmune
      encephalomyelitis.
AB  - T cells have an essential role in the induction of multiple sclerosis and its
      animal model experimental autoimmune encephalomyelitis (EAE). Although for CD4(+)
      T cells it is well established that they contribute to the disease, less is known
      about the role of CD8(+) T cells. Our aim was to determine the individual
      contribution of CD4(+) and CD8(+) T cells in myelin oligodendrocyte glycoprotein
      (MOG)35-55-induced EAE. We investigated MOG35-55-activated CD8(+) T cells to
      clarify their potential to induce or attenuate EAE. We monitored the behavior of
      CD8(+) T cells and their interaction with CD4(+) T cells directly at the site of
      inflammation in the CNS using intravital imaging of the brainstem of EAE-affected
      living anesthetized mice. We found that mice without CD4(+) T cells did not
      develop relevant clinical signs of disease, although CD8(+) T cells were present
      in the CNS of these mice. These CD8(+) T cells displayed reduced motility
      compared with those in the presence of CD4(+) T cells. In mice that harbored
      CD4(+) and CD8(+) T cells, we saw a similar extent of clinical signs of EAE as in
      mice with only CD4(+) T cells. Furthermore, the dynamic motility and viability of
      CD4(+) T cells were not disturbed by CD8(+) T cells in the lesions of these mice.
      Therefore, we conclude that in MOG35-55-induced EAE, CD8(+) T cell accumulation
      in the CNS represents instead an epiphenomenon with no impact on clinical disease
      or on the effects of CD4(+) T cells, the latter being the true inducers of the
      disease. 

PMID- 24123687
TI  - Small molecule inhibitor of antigen binding and presentation by HLA-DR2b as a
      therapeutic strategy for the treatment of multiple sclerosis.
AB  - The strong association of HLA-DR2b (DRB1*1501) with multiple sclerosis (MS)
      suggests this molecule as prime target for specific immunotherapy. Inhibition of
      HLA-DR2b-restricted myelin-specific T cells has the potential to selectively
      prevent CNS pathology mediated by these MHC molecules without undesired global
      immunosuppression. In this study, we report development of a highly selective
      small molecule inhibitor of peptide binding and presentation by HLA-DR2b. PV-267,
      the candidate molecule used in these studies, inhibited cytokine production and
      proliferation of myelin-specific HLA-DR2b-restricted T cells. PV-267 had no
      significant effect on T cell responses mediated by other MHC class II molecules,
      including HLA-DR1, -DR4, or -DR9. Importantly, PV-267 did not induce nonspecific
      immune activation of human PBMC. Lastly, PV-267 showed treatment efficacy both in
      preventing experimental autoimmune encephalomyelitis and in treating established
      disease. The results suggest that blocking the MS-associated HLA-DR2b allele with
      small molecule inhibitors may be a promising therapeutic strategy for the
      treatment of MS. 

PMID- 24123688
TI  - Differential uptake of nanoparticles and microparticles by pulmonary APC subsets
      induces discrete immunological imprints.
AB  - There is increasing interest in the use of engineered particles for biomedical
      applications, although questions exist about their proinflammatory properties and
      potential adverse health effects. Lung macrophages and dendritic cells (DC) are
      key regulators of pulmonary immunity, but little is known about their uptake of
      different sized particles or the nature of the induced immunological imprint. We
      investigated comparatively the immunological imprints of inert nontoxic
      polystyrene nanoparticles 50 nm in diameter (PS50G) and 500 nm in diameter
      (PS500G). Following intratracheal instillation into naive mice, PS50G were
      preferentially taken up by alveolar and nonalveolar macrophages, B cells, and
      CD11b(+) and CD103(+) DC in the lung, but exclusively by DC in the draining lymph
      node (LN). Negligible particle uptake occurred in the draining LN 2 h
      postinstillation, indicating that particle translocation does not occur via
      lymphatic drainage. PS50G but not PS500G significantly increased airway levels of
      mediators that drive DC migration/maturation and DC costimulatory molecule
      expression. Both particles decreased frequencies of stimulatory CD11b(+)MHC class
      II(hi) allergen-laden DC in the draining LN, with PS50G having the more
      pronounced effect. These distinctive particle imprints differentially modulated
      induction of acute allergic airway inflammation, with PS50G but not PS500G
      significantly inhibiting adaptive allergen-specific immunity. Our data show that
      nanoparticles are taken up preferentially by lung APC stimulate
      cytokine/chemokine production and pulmonary DC maturation and translocate to the
      lung-draining LN via cell-associated transport. Collectively, these distinctive
      particle imprints differentially modulate development of subsequent lung immune
      responses. These findings support the development of lung-specific particulate
      vaccines, drug delivery systems, and immunomodulators. 

PMID- 24123689
TI  - Evolution of B cell responses to Clec9A-targeted antigen.
AB  - The response of B cells to Ag targeted to Clec9A on dendritic cells was followed
      using the hapten nitrophenol (NP) conjugated to rat Ig carrier. Injection of
      small amounts of NP conjugated to anti-Clec9A in the absence of adjuvants gave
      high and very prolonged Ab responses, approaching those obtained by high doses of
      nontargeted NP-protein conjugates with alum adjuvant. The response to NP-anti
      Clec9A included the transient formation of germinal centers, maturation of Ab
      affinity, and some memory B cell formation. Serum Ab titers remained high 35 wk
      postimmunization, well after the initial follicular response had faded. The
      results suggest Clec9A-targeting strategies for improving Ab responses to vaccine
      Ags. 

PMID- 24123691
TI  - Disability, despotism, deoxygenation--from exile to Academy member: Nikolai
      Matveevich Kizhner.

PMID- 24123692
TI  - Sleep quality and the metabolic syndrome: the role of sleep duration and
      lifestyle.
AB  - BACKGROUND: This study examined the association between sleep quality and the
      metabolic syndrome and whether if it is independent of sleep duration and if it
      can be explained by lifestyles linked to sleep quality. METHODS: Cross-sectional
      study conducted from 2008 to 2010 with 10 342 individuals representative of the
      population aged >=18 years in Spain. Poor sleep quality was ascertained through
      self-reported difficulty falling asleep, difficulty maintaining sleep and
      sleeping pill consumption. Metabolic syndrome was defined according to the recent
      harmonized definition. Analyses were conducted with logistic regression and
      adjusted for the main confounders. RESULTS: Difficulty falling asleep was
      associated with higher frequency of metabolic syndrome after adjustment for
      sociodemographic variables, lifestyle and diagnosed morbidity [odds ratio (OR) =
      1.25; 95% confidence interval (CI) = 1.06-1.47]. The association was slightly
      attenuated after further adjusting for sleep duration (OR = 1.23; 95% CI = 1.04
      1.46) and held after additional adjustment for energy intake, adherence to a
      Mediterranean dietary pattern, energy spent in physical activity and time
      watching TV (OR = 1.20; 95% CI = 1.01-1.42). No associations were found between
      metabolic syndrome and other sleep quality indicators. Difficulty falling asleep
      was associated with high blood pressure in the fully adjusted analyses (OR =
      1.17; 95% CI = 1.00-1.37) but not with the rest of components of metabolic
      syndrome. CONCLUSIONS: Difficulty falling asleep is associated with metabolic
      syndrome and, in particular, with high blood pressure. This association is
      independent of sleep duration and is not due to lifestyles related to poor sleep.
      This finding should be replicated in prospective studies using objective sleep
      measures; also, the influence of antihypertensive and lipid-lowering drug
      treatment on this association should be further studied.

PMID- 24123693
TI  - Copper-catalyzed borylation of alpha-alkoxy allenes with bis(pinacolato)diboron:
      efficient synthesis of 2-boryl 1,3-butadienes.
AB  - Something solid to build on: 2-Boryl 1,3-butadienes with various substitution
      patterns were formed in good to high yields in a copper-catalyzed borylation of
      alpha-alkoxy allenes with bis(pinacolato)diboron (see scheme; Bn=benzyl,
      pin=pinacolate, L is an N-heterocyclic carbene ligand). The products were found
      to be useful intermediates for the synthesis of cyclic vinyl boranes, alpha,beta
      unsaturated ketones, and functionalized multisubstituted dienes. 

PMID- 24123694
TI  - R2* as a surrogate measure of ferriscan iron quantification in thalassemia.
AB  - PURPOSE: To determine whether R2* values are a consistent predictor of hepatic
      iron concentration (HIC) in thalassemia patients by demonstrating a correlation
      between R2* relaxation rates and FerriScan-determined HIC. MATERIALS AND METHODS:
      Eighty-eight patients with thalassemia major were retrospectively evaluated. All
      patients underwent FerriScan imaging and multiecho gradient echo imaging. The
      results from FerriScan analysis were fitted against R2* estimates using linear
      regression. RESULTS: There was a very strong linear correlation between R2*
      values and FerriScan-determined HIC (Spearman correlation of 0.976; 95%
      confidence interval [CI]: 0.963, 0.984). CONCLUSION: R2* values can predict HIC
      determined by FerriScan using a linear calibration curve. This technique may
      provide a potentially cost-saving alternative for hepatic iron determination and
      improve acceptance by referring physicians.

PMID- 24123695
TI  - A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants.
AB  - The precise mechanisms of antioxidant-mediated longevity are poorly understood.
      We show that an antioxidant treatment can extend the lifespan of Caenorhabditis
      elegans (C. elegans) through the nuclear translocation of the forkhead box O
      transcription factor (FoxO) homolog DAF-16. This pathway was found to involve 3
      phosphoinositide-dependent kinase-1 (PDK-1) and serum- and glucocorticoid
      regulated kinase-1 (SGK-1), distinct from the known oxidative stress-mediated
      mechanism in which FoxO3a translocation is regulated by c-Jun N-terminal kinase
      (JNK) and mammalian sterile 20-like kinase-1 (MST-1). The differences in the
      mechanisms of FoxO activation by antioxidants and oxidants result in differences
      in FoxO phosphorylation and target gene expression. Based on these results, we
      found that a combination of early antioxidant treatment and late oxidant
      treatment is most effective for lifespan extension in C. elegans.

PMID- 24123696
TI  - Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair
      after radiation injury.
AB  - The role of Dclk1(+) tuft cells in the replacement of intestinal epithelia and
      reestablishing the epithelial barrier after severe genotoxic insult is completely
      unknown. Successful restoration requires precise coordination between the cells
      within each crypt subunit. While the mechanisms that control this response remain
      largely uncertain, the radiation model remains an exceptional surrogate for stem
      cell-associated crypt loss. Following the creation of Dclk1-intestinal-epithelial
      deficient Villin-Cre;Dclk1(flox/flox) mice, widespread gene expression changes
      were detected in isolated intestinal epithelia during homeostasis. While the
      number of surviving crypts was unaffected, Villin-Cre;Dclk1(flox/flox) mice
      failed to maintain tight junctions and died at approximately 5 days, where
      Dclk1(flox/flox) mice lived until day 10 following radiation injury. These
      findings suggest that Dclk1 plays a functional role critical in the epithelial
      restorative response.

PMID- 24123697
TI  - Bone marrow uptake of ferumoxytol: a preliminary study in healthy human subjects.
AB  - PURPOSE: To characterize the uptake and elimination of ferumoxytol, an ultrasmall
      superparamagnetic iron oxide (USPIO) agent, in bone marrow of healthy human
      subjects. MATERIALS AND METHODS: Four men and two postmenopausal women, aged 22
      to 57 years, were prospectively included. Simultaneous fat, water, and T2*
      mapping of the proximal femora was performed at 1.5 Tesla using a three
      dimensional multiple gradient echo sequence. After baseline imaging, ferumoxytol
      (Feraheme/Rienso) was injected intravenously at a dose of 5 mg Fe/kg body weight.
      Imaging was repeated at 3 days, 1 month, 3 months, and 5 months after
      administration. RESULTS: Imaging at 3 days revealed large increases in R2* (
      =1/T2*) in hematopoietic marrow and lower average responses in fatty marrow,
      consistent with macrophage-specific uptake. However, certain regions of the
      diaphysis exhibited substantial R2* enhancement despite having very high fat
      content. This suggests the persistence of residual marrow stroma following
      adipose conversion, and may reflect the ability of diaphyseal marrow to adapt
      dynamically to fluctuating demand for hematopoiesis. Follow-up imaging
      demonstrated almost complete R2* recovery within 3 months. CONCLUSION: The
      observed R2* enhancement characteristics support applications for ferumoxytol in
      distinguishing normal or hypercellular marrow from neoplasms, infection and
      inflammation. Further studies are warranted in specific patient populations.

PMID- 24123698
TI  - High-pressure synthesis and characterization of new actinide borates, AnB4O8
      (An=Th, U).
AB  - New actinide borates ThB4O8 and UB4O8 were synthesized under high-pressure, high
      temperature conditions (5.5 GPa/1100  degrees C for thorium borate, 10.5 GPa/1100
      degrees C for the isotypic uranium borate) in a Walker-type multianvil apparatus
      from their corresponding actinide oxide and boron oxide. The crystal structure
      was determined on basis of single-crystal X-ray diffraction data that were
      collected at room temperature. Both compounds crystallized in the monoclinic
      space group C2/c (Z=4). Lattice parameters for ThB4O8: a=1611.3(3), b=419.86(8),
      c=730.6(2) pm; beta=114.70(3) degrees ; V=449.0(2) A(3); R1=0.0255, wR2=0.0653
      (all data). Lattice parameters for UB4O8: a=1589.7(3), b=422.14(8), c=723.4(2)
      pm; beta=114.13(3) degrees ; V=443.1(2) A(3); R1=0.0227, wR2=0.0372 (all data).
      The new AnB4O8 (An=Th, U) structure type is constructed from corner-sharing BO4
      tetrahedra, which form layers in the bc plane. One of the four independent oxygen
      atoms is threefold-coordinated. The actinide cations are located between the
      boron-oxygen layers. In addition to Raman spectroscopic investigations, DFT
      calculations were performed to support the assignment of the vibrational bands.

PMID- 24123699
TI  - Anger and health in dementia caregivers: exploring the mediation effect of
      optimism.
AB  - Although previous studies indicate a negative association between caregivers'
      anger and health, the potential mechanisms linking this relationship are not yet
      fully understood. The aim of this study was to explore the potential mediating
      role of optimism in the relationship between anger and caregivers' physical
      health. Dementia caregivers (n = 108) were interviewed and filled out instruments
      assessing their anger (reaction), optimism and health (vitality). A mediational
      model was tested to determine whether optimism partially mediated the
      relationship between anger and vitality. Angry reaction was negatively associated
      with optimism and vitality; optimism was positively associated with vitality.
      Finally, the relationship between angry reaction and vitality decreased when
      optimism was entered simultaneously. A non-parametric bootstrap approach
      confirmed that optimism significantly mediated some of the relationship between
      angry reaction and vitality. These findings suggest that low optimism may help
      explain the association between caregivers' anger and reduced sense of vitality.
      The results provide a specific target for intervention with caregivers.

PMID- 24123702
TI  - Common quantitative trait locus downstream of RETN gene identified by genome-wide
      association study is associated with risk of type 2 diabetes mellitus in Han
      Chinese: a Mendelian randomization effect.
AB  - OBJECTIVE: Plasma resistin level is a potential molecular link between obesity
      and diabetes. Causal role of resistin, type 2 diabetes mellitus (T2DM) and
      genetic variants have not been thoroughly investigated. Therefore, we conducted a
      genome-wide association study (GWAS) to identify quantitative trait loci
      associated with resistin levels and investigated whether these variants were
      prospectively associated with the development of metabolic syndrome (MetS) and
      T2DM in an independent community-based cohort, the CardioVascular Disease risk
      FACtors Two-township Study (CVDFACTS). RESEARCH DESIGN AND METHODS: We genotyped
      382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 chips and
      searched for quantitative trait loci (QTLs) of resistin in the 1(st) stage GWAS
      and confirmed the finding in another 559 YOH subjects. Logistic regression was
      used to examine the Mendelian randomization effects between genotypes of
      confirmed QTLs and metabolic outcomes in 3400 subjects of CVDFACTS. RESULTS: Two
      single nucleotide polymorphisms (SNP) (rs3745367 and rs1423096) were
      significantly associated with resistin levels (p = 5.52 * 10(-15) and p = 2.54 *
      10(-20) ) and replicated in another 559 YOH subjects (p = 1.29 * 10(-3) and p =
      1.13 * 10(-7) ), respectively. The SNP rs1423096 was further associated with the
      levels of HDL-C (p = 0.006), the risk of MetS (OR = 2.21, p = 0.0034) and T2DM
      (OR = 1.62, p = 0.0063) in the CVDFACTS. People with the haplotypes A-G and G-G
      determined by rs3745367 and rs1423096 showed a significantly increased T2DM risk
      (p = 0.0068 and p = 0.0035, respectively) compared with those with A-A haplotype.
      CONCLUSION: We have found that rs3745367 and rs1423096 on the RETN gene were
      significantly associated with resistin levels. However, rs1423096, downstream of
      RETN, seems to be associated with MetS and T2DM risk more so than rs3745367. The
      established genotype-disease association points to a causal association of
      resistin and T2DM.

PMID- 24123703
TI  - Encomium: Giovanni Neri--polyhedral and down-to-earth mentor.

PMID- 24123704
TI  - Season of birth in obsessive-compulsive disorder.
AB  - BACKGROUND: Effects of season of birth (SOB) have been documented in numerous
      neuropsychiatric disorders. To date, few studies have evaluated this issue in
      obsessive-compulsive disorder (OCD). The aim of this study was to investigate the
      birth seasonality in OCD. METHODS: This study was based on Taiwan National Health
      Insurance Research Database. Data for the birth-year period 1956-1991 were
      extracted for analysis (273,837 males and 292,207 females). The International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), code
      300.3 was used as the diagnosis of OCD. Birth seasonality was compared between
      the OCD patients (519 males and 528 females) and the general population. RESULTS:
      The birth distributions across the 12 months were significantly different between
      the OCD patients and the general population (P-value for the Walter & Elwood's
      test = .04). A significant decrease of births from March to July and an excess
      from August to November in OCD patients as compared to the general population was
      noted (the relative risk of these months vs. the rest months of the year: 0.85
      (95% CI 0.74-0.96) and 1.19 (95% CI 1.05-1.36). Effects of SOB in OCD were
      present in males (P-value for the Walter & Elwood's test = .03) but not in
      females. CONCLUSION: The findings support an effect of SOB in people with OCD,
      especially for men.

PMID- 24123705
TI  - Cytoplasmic extension peptide of Pichia pastoris glucose sensor Gss1 is not
      compulsory for glucose signalling.
AB  - In the methylotrophic yeast, Pichia pastoris, Gss1 protein is a glucose sensor
      involved in pexophagy, glucose utilization and glucose catabolite repression.
      This study identifies that deletion of 150 residues of Gss1 affects slightly
      glucose catabolite repression and pexophagy, while maintaining signalling
      function of Gss1. Substitution of one conserved amino acid R180K of Gss1 protein
      has no visible phenotype, in contrast to corresponding changes in glucose sensors
      from other yeast species. We suggest that C-terminal cytoplasmic extension of
      PpGss1plays different role to that of its homologs in Saccharomyces cerevisiae
      and Hansenula polymorpha. 

PMID- 24123706
TI  - Incidence and implications of idiopathic thrombocytopenia following transcatheter
      aortic valve replacement with the Edwards Sapien((c)) valves: a single center
      experience.
AB  - OBJECTIVES: To determine the incidence and etiology of thrombocytopenia following
      transcatheter Aortic valve replacement (TAVR). BACKGROUND: the use of TAVR in the
      United States has grown rapidly. Anecdotally, thrombocytopenia following TAVR
      with the Sapien valves has been observed, though little is known about this
      phenomenon. METHODS: All patients treated with TAVR using a Sapien valve or who
      underwent isolated balloon aortic valvuloplasty (BAV) at Brigham and Women's
      Hospital from October 2009 through November 2012 were analyzed. Post-procedure
      thrombocytopenia severity was stratified as none (>150,000 cells/MUL), mild (100
      150,000), and moderate to severe (<100,000). Summary statistics and simple
      comparisons were evaluated. Linear regression models were used to identify
      patient or procedural factors associated with platelet count nadir. RESULTS: 112
      TAVR and 105 BAV patients were analyzed. Following TAVR the prevalence of
      thrombocytopenia was 69% and the incidence of new thrombocytopenia was 45%
      compared to 37% and 17% respectively following BAV (P < 0.01). Similar results
      were found across all strata of thrombocytopenia severity. Post-TAVR platelet
      nadirs were greater by 1,840 cells/MUL for each 1% increase in STS score (P =
      0.03) and 670 cells/MUL greater for each 1 mmHg increase in pre-TAVR mean aortic
      stenosis gradient. Among TAVR patients, thrombocytopenia appears to spontaneously
      resolve an average of 8 days post-procedure. No differences in clinical outcomes
      based on thrombocytopenia severity were observed except for an increased use of
      blood products (P = 0.05). CONCLUSIONS: Thrombocytopenia following TAVR with the
      Edwards' Sapien valves is a frequent but generally self-limited process. The
      etiology of this phenomenon is unknown.

PMID- 24123707
TI  - Formation of metallic mercury during photodegradation/photodarkening of alpha
      HgS: electrochemical evidence.

PMID- 24123708
TI  - Crystallization of tungsten trioxide having small mesopores: highly efficient
      photoanode for visible-light-driven water oxidation.

PMID- 24123710
TI  - Tumor heterogeneity makes AML a "moving target" for detection of residual
      disease.
AB  - Detection of minimal residual disease is recognized as an important post-therapy
      risk factor in acute myeloid leukemia patients. Two most commonly used methods
      for residual disease monitoring are real time quantitative polymerase chain
      reaction and multiparameter flow cytometry. Results so far are very promising,
      whereby it is likely that minimal residual disease results will enable to guide
      future post-remission treatment strategies. However, the leukemic clone may
      change between diagnosis and relapse due to instability of the tumor cells. This
      instability may already be evident at diagnosis if different subpopulations of
      tumor cells coexist. Such tumor heterogeneity, which may be reflected by
      immunophenotypic, molecular and/or cytogenetic changes, can have important
      consequences for minimal residual disease detection, since false-negative results
      can be expected to be the result of losses of aberrancies used as minimal
      residual disease markers. In this review the role of such changes in minimal
      residual disease monitoring is explored. Furthermore, possible causes of tumor
      instability are discussed, whereby the concept of clonal selection and expansion
      of a chemotherapy resistant subpopulation is highlighted. Accordingly, detailed
      knowledge of the process of clonal evolution is required to improve both minimal
      residual disease risk stratification and patient outcome. (c) 2013 Clinical
      Cytometry Society.

PMID- 24123709
TI  - An osteopontin-integrin interaction plays a critical role in directing
      adipogenesis and osteogenesis by mesenchymal stem cells.
AB  - An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem
      cells (MSCs) has been shown to be related to various human metabolic diseases,
      such as obesity and osteoporosis; however, the underlying mechanisms remain
      elusive. We found that the interaction between osteopontin (OPN), an arginine
      glycine-aspartate-containing glycoprotein, and integrin alphav/beta1 plays a
      critical role in the lineage determination of MSCs. Although OPN is a well
      established marker during osteogenesis, its role in MSC differentiation is still
      unknown. Our study reveals that blockade of OPN function promoted robust
      adipogenic differentiation, while inhibiting osteogenic differentiation. Re
      expression of OPN restored a normal balance between adipogenesis and osteogenesis
      in OPN(-/-) MSCs. Retarded bone formation by OPN(-/-) MSCs was also verified by
      in vivo implantation with hydroxyapatite-tricalcium phosphate, a bone-forming
      matrix. The role of extracellular OPN in MSC differentiation was further
      demonstrated by supplementation and neutralization of OPN. Blocking well-known
      OPN receptors integrin alphav/beta1 but not CD44 also affected MSC
      differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling
      pathway through integrin alphav/beta1. Consistent with these in vitro results,
      OPN(-/-) mice had a higher fat to total body weight ratio than did wild-type
      mice. Therefore, our study demonstrates a novel role for OPN-integrin
      alphav/beta1 in regulating MSC differentiation.

PMID- 24123711
TI  - A comparison of statistical methods for combining relative bioactivities from
      parallel line bioassays.
AB  - This paper compares the ordinary unweighted average, weighted average, and
      maximum likelihood methods for estimating a common bioactivity from multiple
      parallel line bioassays. Some of these or similar methods are also used in meta
      analysis. Based on a simulation study, these methods are assessed by comparing
      coverage probabilities of the true relative bioactivity and the length of the
      confidence intervals computed for these methods. The ordinary unweighted average
      method outperforms all statistical methods by consistently giving the best
      coverage probability but with somewhat wider confidence intervals. The weighted
      average methods give good coverage and smaller confidence intervals when
      combining homogeneous bioactivities. For heterogeneous bioactivities, these
      methods work well when a liberal significance level for testing homogeneity of
      bioactivities is used. The maximum likelihood methods gave good coverage when
      homogeneous bioactivities were considered. Overall, the preferred methods are the
      ordinary unweighted average and two weighted average methods that were
      specifically developed for bioassays.

PMID- 24123712
TI  - Quantitative measurement of femoral condyle cartilage in the knee by MRI:
      validation study by multireaders.
AB  - PURPOSE: To determine reproducibility of the femoral condyle cartilage volume
      (CV) in cross-sectional and longitudinal studies using various 3D imaging
      techniques at 1.5 T and 3 T. MATERIALS AND METHODS: In 21 subjects with
      osteoarthritis, magnetic resonance imaging (MRI) including four different
      sequences (sagittal 3D fat suppressed spoiled gradient-echo [SPGR] at 1.5 T, fat
      suppressed fast low angle shot [FLASH] at 3 T, water-excitation dual echo steady
      state [DESS] at 3 T, and water-excitation multiecho data image combination
      [MEDIC] at 3 T) were acquired at baseline and ~1 year later. The CV measured
      using semiautomated segmentation software by three readers was analyzed. RESULTS:
      The mean of the interclass correlation coefficient between each reader from SPGR,
      FLASH, DESS, and MEDIC was 0.899, 0.948, 0.943, and 0.954, respectively. The mean
      CV (*10(4) mm(3) ) measured by each reader from SPGR/FLASH/DESS/MEDIC sequences
      was the following in this order: 1.34/1.52/1.50/1.35, 1.21/1.43/1.40/1.27,
      1.22/1.37/1.36/1.22, and 1.17/1.36/1.35/1.21 by readers 1, 2, 3 (first analysis),
      and 3 (second analysis), respectively. There was no statistically significant
      difference in CV between any readers in any sequences. The CV measured on FLASH
      and DESS tended to be greater than that on SPGR or MEDIC. CONCLUSION: Inter- and
      intraobserver reproducibility of cartilage segmentation using semiautomated
      software was validated. Although there was no statistical significance, there was
      a tendency of under- or overestimating CV by each sequence.

PMID- 24123713
TI  - High resolution integrative analysis reveals widespread genetic and epigenetic
      changes after chronic in-vitro acid and bile exposure in Barrett's epithelium
      cells.
AB  - Barrett's epithelium (BE) is a premalignant condition resulting from chronic
      gastroesophageal reflux that may progress to esophageal adenocarcinoma (EAC).
      Early intervention holds promise in preventing BE progression. However,
      identification of high-risk BE patients remains challenging due to inadequate
      biomarkers for early diagnosis. We investigated the effect of prolonged chronic
      acid and bile exposure on transcriptome, methylome, and mutatome of cells in an
      in-vitro BE carcinogenesis (BEC) model. Twenty weeks acid and bile exposed cells
      from the BEC model (BEC20w) were compared with their naive predecessors HiSeq
      Illumina based RNA sequencing was performed on RNA from both the cells for gene
      expression and mutational analysis. HELP Tagging Assay was performed for DNA
      methylation analysis. Ingenuity pathway, Gene Ontology, and KEGG PATHWAY analyses
      were then performed on datasets. Widespread aberrant genetic and epigenetic
      changes were observed in the BEC20w cells. Combinatorial analyses revealed 433
      from a total of 863 downregulated genes had accompanying hypermethylation of
      promoters. Simultaneously, 690 genes from a total of 1,492 were upregulated with
      accompanying promoter hypomethylation. In addition, 763 mutations were identified
      on 637 genes. Ingenuity pathway analysis, Gene Ontology, and KEGG PATHWAY
      analyses associated the genetic and epigenetic changes in BEC20w cells with
      cellular and biological functions. Integration of high resolution comparative
      analyses of naive BAR-T and BEC20w cells revealed striking genetic and epigenetic
      changes induced by chronic acid and bile exposure that may disrupt normal
      cellular functions and promote carcinogenesis. This novel study reveals several
      potential targets for future biomarkers and therapeutic development.

PMID- 24123714
TI  - beta-Cryptoxanthin uptake in THP-1 macrophages upregulates the CYP27A1 signaling
      pathway.
AB  - SCOPE: Mitochondrial sterol 27-hydroxylase (CYP27A1), a mediator of cholesterol
      homeostasis, is reported to exhibit antiatherogenic properties. Many studies
      suggested that all-trans retinoic acid can be used to treat atherosclerosis
      through retinoic acid receptor (RAR)-mediated upregulation of CYP27A1 expression.
      In this study, we hypothesized that beta-cryptoxanthin (beta-cry), as a natural
      ligand of RAR, might act as antiatherogenic agent by upregulating CYP27A1.
      METHODS AND RESULTS: We found that beta-cry treatment significantly upregulated
      genes involved in the uptake, transport, and metabolism of retinoids and the
      signaling pathway of CYP27A1 expression in THP-1 macrophages as detected by
      microarray analysis. Meanwhile, intracellular levels of beta-cry were correlated
      to the concentration and exposure time of the treatment. The expression of genes,
      involved in signaling pathway of CYP27A1, was dramatically decreased due to
      repressed activity of RAR. Higher level of 27-hydroxycholesterol was detected in
      beta-cry-treated macrophages by HPLC. Docking simulation showed that beta-cry
      could interact with cellular retinoic acid binding protein 2. These findings were
      further confirmed through microarray results. CONCLUSION: Our results provide
      strong evidence that beta-cry can be actively taken up by THP-1 macrophages and
      exhibits antiatherogenic effect on THP-1 macrophages by inducing CYP27A1
      expression via RAR.

PMID- 24123715
TI  - Depressive mood modulates the anterior lateral CA1 and DG/CA3 during a pattern
      separation task in cognitively intact individuals: a functional MRI study.
AB  - Although patients with major depressive disorder typically have a reduced
      hippocampal volume, particularly in the cornu ammonis 1 (CA1), animal studies
      suggest that depressive mood is related to the dentate gyrus (DG). In this study,
      our objective was to clarify which hippocampal subregions are functionally
      associated with depressive mood in humans. We conducted a functional MRI (fMRI)
      study on 27 cognitively intact volunteers. Subjects performed a modified version
      of a delayed matching-to-sample task in an MRI scanner to investigate pattern
      separation-related activity during each phase of encoding, delay, and retrieval.
      In each trial, subjects learned a pair of sample cues. Functional MR images were
      acquired at a high spatial resolution, focusing on the hippocampus. Subjects also
      completed the Beck Depression Inventory (BDI), a questionnaire about depressive
      mood. Depending on the similarity between sample cues, activity in the DG/CA3 and
      medial CA1 in the anterior hippocampus changed only during encoding. Furthermore,
      the DG/CA3 region was more active during successful encoding trials compared to
      false trials. Activity in the DG/CA3 and lateral CA1 was negatively correlated
      with BDI scores. These results suggest that the DG/CA3 is the core region for
      pattern separation during the encoding phase and interacts with the medial CA1,
      depending on the similarity of the stimuli, to achieve effective encoding.
      Impaired activity in the DG/CA3, as well as in the lateral CA1, was found to be
      associated with depressive symptoms, even at a subclinical level.

PMID- 24123717
TI  - Copper(I)-catalyzed alkylation of aryl- and alkenylsilanes activated by
      intramolecular coordination of an alkoxide.

PMID- 24123716
TI  - Novel Aeruginosin-865 from Nostoc sp. as a potent anti-inflammatory agent.
AB  - Aeruginosin-865 (Aer-865), isolated from terrestrial cyanobacterium Nostoc sp.
      Lukesova 30/93, is the first aeruginosin-type peptide containing both a fatty
      acid and a carbohydrate moiety, and is the first aeruginosin to be found in the
      genus Nostoc. Mass spectrometry, chemical and spectroscopic analysis as well as
      one- and two-dimensional NMR and chiral HPLC analysis of Marfey derivatives were
      applied to determine the peptidic sequence: D-Hpla, D-Leu, 5-OH-Choi, Agma, with
      hexanoic and mannopyranosyl uronic acid moieties linked to Choi. We used an
      AlphaLISA assay to measure the levels of proinflammatory mediators IL-8 and ICAM
      1 in hTNF-alpha-stimulated HLMVECs. Aer-865 showed significant reduction of both:
      with EC50 values of (3.5+/-1.5) MUg mL(-1) ((4.0+/-1.7) MUM) and (50.0+/-13.4)
      MUg mL(-1) ((57.8+/-15.5) MUM), respectively. Confocal laser scanning microscopy
      revealed that the anti-inflammatory effect of Aer-865 was directly associated
      with inhibition of NF-kappaB translocation to the nucleus. Moreover, Aer-865 did
      not show any cytotoxic effect.

PMID- 24123718
TI  - Rate control of cell sheet recovery by incorporating hydrophilic pattern in
      thermoresponsive cell culture dish.
AB  - Thready stripe-polyacrylamide (PAAm) pattern was fabricated on a thermoresponsive
      poly(N-isopropylacrylamide) (PIPAAm) surface, and their surface properties were
      characterized. A PIPAAm surface spin-coated with positive photoresist was
      irradiated through a 5 um/5 um or a 10 um/10-um black and white striped
      photomask, resulting in the radical polymerization of AAm on the photoirradiated
      area. After staining with Alexa488 bovine serum albumin, the stripe-patterned
      surface was clearly observed and the patterned surface was also observed by a
      phase contrast image of an atomic force microscope. NIH-3T3 (3T3) single cells
      were able to be cultured at 37 degrees C on the patterned surfaces as well as on
      a PIPAAm surface without pattern, and the detachment of adhered cells was more
      rapidly from the patterned surface after reducing temperature. Furthermore, the
      rate of detachment of 3T3 confluent cell sheet on the patterned surface was
      accelerated, compared with on a conventional PIPAAm surface under the static
      condition. The rate control of cell sheet recovery should contribute the
      preservations of cell phenotype and biological functions of cell sheet for
      applying to clinical trials.

PMID- 24123719
TI  - Giovanni Neri.

PMID- 24123720
TI  - Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas -
      a meta-analysis from randomized clinical trials.
AB  - BACKGROUND: Dipeptidyl peptidase-IV (DPP-4) inhibitors and sulfonylureas are two
      important second-line anti-diabetic agents. The objective of this research was to
      evaluate the efficacy and safety of DPP-4 inhibitors compared with sulfonylureas
      by meta-analytic approach of available randomized studies. METHODS: We searched
      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases
      up to 30 June 2013, collecting all randomized clinical trials with a treatment
      duration of >=18weeks. Data on glycated haemoglobin (HbA1c ), body weight,
      hypoglycaemia, total adverse events, and cardiovascular events were retrieved and
      analysed. RESULTS: The analysis included 12 randomized studies comprising 10 982
      patients with type 2 diabetes mellitus. On the basis of meta-analysis,
      sulfonylureas lowered HbA1c significantly more than DPP-4 inhibitors with
      weighted mean difference (WMD) of 0.105 [95% confidence interval (CI) 0.103 to
      0.107]. The results were consistent in trials with longer (>32 weeks) or shorter
      (<=32 weeks) duration; however, DPP-4 inhibitors showed greater reduction in
      HbA1c compared with the second-generation sulfonylureas and in patients with
      baseline eGFR < 50 mL/min/1.73 m(2) . Patients treated with DPP-4 inhibitors are
      less likely to achieve HbA1c  < 7% compared with sulfonylureas [Mantel-Haenszel
      odds ratio (MH-OR) 0.91; 95% CI 0.84 to 0.99]. DPP-4 xinhibitors were associated
      with a reduction in body weight (WMD -1.652; 95% CI -1.658 to -1.646) and lower
      risk of hypoglycaemia (MH-OR, 0.13; 95% CI 0.11 to 0.16), total adverse events
      (MH-OR, 0.79; 95% CI 0.72 to 0.87), and cardiovascular events (MH-OR, 0.53; 95%
      CI 0.32 to 0.87) compared with sulfonylureas. CONCLUSION: Although DPP-4
      inhibitors are less efficacious compared with sulfonylureas, they demonstrate a
      beneficial effect on body weight, episodes of hypoglycaemia, and total adverse
      events.

PMID- 24123721
TI  - In vitro validation of flow measurement with phase contrast MRI at 3 tesla using
      stereoscopic particle image velocimetry and stereoscopic particle image
      velocimetry-based computational fluid dynamics.
AB  - PURPOSE: To validate conventional phase-contrast MRI (PC-MRI) measurements of
      steady and pulsatile flows through stenotic phantoms with various degrees of
      narrowing at Reynolds numbers mimicking flows in the human iliac artery using
      stereoscopic particle image velocimetry (SPIV) as gold standard. MATERIALS AND
      METHODS: A series of detailed experiments are reported for validation of MR
      measurements of steady and pulsatile flows with SPIV and CFD on three different
      stenotic models with 50%, 74%, and 87% area occlusions at three sites: two
      diameters proximal to the stenosis, at the throat, and two diameters distal to
      the stenosis. RESULTS: Agreement between conventional spin-warp PC-MRI with
      Cartesian read-out and SPIV was demonstrated for both steady and pulsatile flows
      with mean Reynolds numbers of 130, 160, and 190 at the inlet by evaluating the
      linear regression between the two methods. The analysis revealed a correlation
      coefficient of > 0.99 and > 0.96 for steady and pulsatile flows, respectively.
      Additionally, it was found that the most accurate measures of flow by the
      sequence were at the throat of the stenosis (error < 5% for both steady and
      pulsatile mean flows). The flow rate error distal to the stenosis was primarily
      found to be a function of narrowing severity including dependence on proper Venc
      selection. CONCLUSION: SPIV and CFD provide excellent approaches to in vitro
      validation of new or existing PC-MRI flow measurement techniques.

PMID- 24123722
TI  - Effectiveness of Japanese SHARE model in improving Taiwanese healthcare
      personnel's preference for cancer truth telling.
AB  - BACKGROUND: Communication skills training (CST) based on the Japanese SHARE model
      of family-centered truth telling in Asian countries has been adopted in Taiwan.
      However, its effectiveness in Taiwan has only been preliminarily verified. This
      study aimed to test the effect of SHARE model-centered CST on Taiwanese
      healthcare providers' truth-telling preference, to determine the effect size, and
      to compare the effect of 1-day and 2-day CST programs on participants' truth
      telling preference. METHOD: For this one-group, pretest-posttest study, 10 CST
      programs were conducted from August 2010 to November 2011 under certified
      facilitators and with standard patients. Participants (257 healthcare personnel
      from northern, central, southern, and eastern Taiwan) chose the 1-day (n = 94) or
      2-day (n = 163) CST program as convenient. Participants' self-reported truth
      telling preference was measured before and immediately after CST programs, with
      CST program assessment afterward. RESULTS: The CST programs significantly
      improved healthcare personnel's truth-telling preference (mean pretest and
      posttest scores +/- standard deviation (SD): 263.8 +/- 27.0 vs. 281.8 +/- 22.9, p
      < 0.001). The CST programs effected a significant, large (d = 0.91) improvement
      in overall truth-telling preference and significantly improved method of
      disclosure, emotional support, and additional information (p < 0.001).
      Participation in 1-day or 2-day CST programs did not significantly affect
      participants' truth-telling preference (p > 0.05) except for the setting
      subscale. Most participants were satisfied with the CST programs (93.8%) and were
      willing to recommend them to colleagues (98.5%). CONCLUSIONS: The SHARE model
      centered CST programs significantly improved Taiwanese healthcare personnel's
      truth-telling preference. Future studies should objectively assess participants'
      truth-telling preference, for example, by cancer patients, their families, and
      other medical team personnel and at longer times after CST programs.

PMID- 24123723
TI  - The effect of oxidation on the mechanical response and microstructure of porcine
      aortas.
AB  - Reactive oxygen species (ROS), a product of many cellular functions, has been
      implicated in many age-related pathophysiological processes, including
      cardiovascular disease. The arterial proteins collagen and elastin may also
      undergo structural and functional changes due to damage caused by ROS. This study
      examined the effect of oxidation on the mechanical response of porcine aortas and
      aorta elastin and the associated changes in structural protein ultrastructure as
      a step in exploring the role of molecular changes in structural proteins with
      aging on elastic artery function. We examined the change in mechanical properties
      of aorta samples after various oxidation times as a first step in understanding
      how the oxidative environment associated with aging could impact mechanical
      properties of arterial structural proteins. We used confocal microscopy to
      visualize how the microstructure of isolated elastin changed with oxidation. We
      find that short term oxidation of elastin isolated from aortas leads to an
      increase in material stiffness, but also an increase in the fiber diameter,
      increase in void space in the matrix, and a decrease in the fiber orientation,
      possibly due to fiber cross-linking. The short term effects of oxidation on
      arterial collagen is more complex, with increase in material stiffness seen in
      the collagen region of the stress stretch curve at low extents of oxidation, but
      not at high levels of oxidation. These results may provide insight into the
      relationship between oxidative damage to tissue associated with aging and
      disease, structure of the arterial proteins elastin and collagen, and arterial
      mechanical properties and function.

PMID- 24123724
TI  - Expression of embryonic stem cell markers and osteogenic differentiation
      potential in cells derived from periodontal granulation tissue.
AB  - The aim of this study was to identify if cells obtained from periodontal
      granulation tissue possess embryonic stem cell properties and osteogenic
      capacities in vitro. Periodontal granulation tissue was removed from one
      furcation and one infrabony defect (FGTC/IGTC-furcation/infrabony defect derived
      granulation tissue cells) of six patients. The extracted tissues were treated
      with collagenase/dispase solution, cultured and passaged twice, while a fraction
      of them was bacteriologically analyzed. Upon reaching confluence, total RNA was
      extracted, followed by cDNA synthesis and real-time PCR analysis. Gene expression
      levels of collagen type I, alkaline phosphatase (ALP), and the embryonic stem
      cell markers Nanog, Oct-4, Rex-1 and Sox-2 were measured, calibrated against the
      housekeeping gene GAPDH. Further, osteogenic differentiation was induced.
      Mineralized matrix formation was confirmed by von Kossa staining, and ALP
      activity was measured colorimetrically. The total bacterial load amounted to 9.4
      +/- 14.6 * 10(6) counts/mg of tissue for IGTC, and 11.1 +/- 6.1 * 10(6) 
      counts/of tissue for FGTC. Among the embryonic stem cell markers (FGTC/IGTC),
      Nanog was most highly expressed (3.48 +/- 1.2/5.85 +/- 5.7), followed by Oct-4
      (1.79 +/- 0.69/2.85 +/- 2.5), Sox-2 (0.66 +/- 0.3/1.26 +/- 1.4) and Rex-1 (0.06
      +/- 0.0/0.04 +/- 0.0). The osteogenic differentiation process was positive in
      both FGTC and IGTC, judged by increased von Kossa staining, and elevated ALP
      activity and gene expression. This study provides evidence that infected
      periodontal granulation tissue harbors cells expressing embryonic stem cell
      markers, and exhibiting osteogenic capacities when in culture in vitro.

PMID- 24123726
TI  - Gene-based therapies of neuromuscular disorders: an update and the pivotal role
      of patient organizations in their discovery and implementation.
AB  - This review updates the state-of-the art accomplishments of the multifaceted gene
      based therapies, which include DNA or RNA as either therapeutic tools or targets
      for the treatment of neuromuscular diseases. It also provides insights into the
      key role that patient organizations have played in research and development; in
      particular, by addressing bottlenecks and generating boundary conditions that
      have contributed to scientific breakthroughs, and the effectiveness of innovation
      processes. Several gene therapy methods have reached the clinical stage and are
      now addressing both specific and classical issues related to this novel
      technology. Not ready yet for clinical application, genome editing is at its
      infancy. More rapidly progressing, RNA-based therapeutics, and especially exon
      skipping, exon inclusion and stop codon readthrough strategies, are about to move
      to the market. Most importantly, patients were at the forefront of this discovery
      process, from basic knowledge to innovation and translational research in a
      rapidly growing field of unmet medical needs. In recent years, Duchenne muscular
      dystrophy was the fertile ground for new therapeutic concepts that have been
      extended to other neuromuscular disorders, such as spinal muscular atrophy,
      myotonic dystrophies or fascioscapulohumeral dystrophy. In line with their
      longstanding policy, patient organizations will keep working in a proactive
      manner to bring together all stakeholders with a view to working out truly
      therapeutic solutions over a long-term perspective.

PMID- 24123725
TI  - Drying and storage effects on poly(ethylene glycol) hydrogel mechanical
      properties and bioactivity.
AB  - Hydrogels based on poly(ethylene glycol) (PEG) are increasingly used in
      biomedical applications because of their ability to control cell-material
      interactions by tuning hydrogel physical and biological properties. Evaluation of
      stability after drying and storage are critical in creating an off-the-shelf
      biomaterial that functions in vivo according to original specifications. However,
      there has not been a study that systematically investigates the effects of
      different drying conditions on hydrogel compositional variables. In the first
      part of this study, PEG-diacrylate hydrogels underwent common processing
      procedures (vacuum-drying, lyophilizing, hydrating then vacuum-drying), and the
      effect of this processing on the mechanical properties and swelling ratios was
      measured. Significant changes in compressive modulus, tensile modulus, and
      swelling ratio only occurred for select processed hydrogels. No consistent trends
      were observed after processing for any of the formulations tested. The effect of
      storage conditions on cell adhesion and spreading on collagen- and streptococcal
      collagen-like protein (Scl2-2)-PEG-diacrylamide hydrogels was then evaluated to
      characterize bioactivity retention after storage. Dry storage conditions
      preserved bioactivity after 6 weeks of storage; whereas, storage in PBS
      significantly reduced bioactivity. This loss of bioactivity was attributed to
      ester hydrolysis of the protein linker, acrylate-PEG-N-hydroxysuccinimide. These
      studies demonstrate that these processing methods and dry storage conditions may
      be used to prepare bioactive PEG hydrogel scaffolds with recoverable
      functionality after storage.

PMID- 24123727
TI  - Maternal reporting of prenatal ultrasounds among women in the National Birth
      Defects Prevention Study.
AB  - BACKGROUND: Increased availability and usage of ultrasound screening have led to
      improved identification of fetal structural abnormalities prenatally. Few
      population-based studies have been published on prenatal detection for structural
      birth defects in the United States. The aim of this study is to determine the
      frequency of maternal reporting of abnormal prenatal ultrasounds for selected
      birth defects and to investigate associated maternal characteristics. METHODS:
      Participants included 4013 mothers enrolled in the National Birth Defects
      Prevention Study who carried a fetus with at least one of 14 structural birth
      defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were
      based on maternal report and computed for isolated and multiple defects.
      Associations between maternal characteristics and abnormal prenatal ultrasounds
      were assessed using logistic regression. RESULTS: Overall, 46% of participants
      reported an abnormal ultrasound. Infants with omphalocele, anencephaly,
      gastroschisis, and renal agenesis were more likely to have abnormal prenatal
      ultrasounds than those with cleft and limb abnormalities. Hispanic women were
      less likely to report abnormal prenatal ultrasounds of birth defects than
      Caucasians, as were women who had a body mass index >= 30 kg/m(2) compared with
      those with a normal body mass index. CONCLUSION: Of the 14 selected birth defects
      in this study, less than half were reported by mothers of affected infants to
      have had an abnormal ultrasound during pregnancy. The frequency of reporting
      abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity,
      and maternal body mass index status.

PMID- 24123728
TI  - Plant polyphenol induced cell death in human cancer cells involves mobilization
      of intracellular copper ions and reactive oxygen species generation: a mechanism
      for cancer chemopreventive action.
AB  - SCOPE: Anticancer polyphenolic nutraceuticals from fruits, vegetables, and spices
      are generally recognized as antioxidants, but can be prooxidants in the presence
      of copper ions. We earlier proposed a mechanism for such activity of polyphenols
      and now we provide data in multiple cancer cell lines in support of our
      hypothesis. METHODS AND RESULTS: Through multiple assays, we show that
      polyphenols luteolin, apigenin, epigallocatechin-3-gallate, and resveratrol are
      able to inhibit cell proliferation and induce apoptosis in different cancer cell
      lines. Such cell death is prevented to a significant extent by cuprous chelator
      neocuproine and reactive oxygen species scavengers. We also show that normal
      breast epithelial cells, cultured in a medium supplemented with copper, become
      sensitized to polyphenol-induced growth inhibition. CONCLUSION: Since the
      concentration of copper is significantly elevated in cancer cells, our results
      strengthen the idea that an important anticancer mechanism of plant polyphenols
      is mediated through intracellular copper mobilization and reactive oxygen species
      generation leading to cancer cell death. Moreover, this prooxidant
      chemopreventive mechanism appears to be a mechanism common to several polyphenols
      with diverse chemical structures and explains the preferential cytotoxicity of
      these compounds toward cancer cells.

PMID- 24123729
TI  - Gonadectomy increases neurogenesis in the male adolescent rhesus macaque
      hippocampus.
AB  - New neurons are continuously produced in the subgranular zone of the adult
      hippocampus and can modulate hippocampal plasticity across life. Adolescence is
      characterized by dramatic changes in sex hormone levels, and social and emotional
      behaviors. It is also an age for increased risk of psychiatric disorders,
      including schizophrenia, which may involve altered hippocampal neurogenesis. The
      extent to which testosterone and other testicular hormones modulate hippocampal
      neurogenesis and adolescent behavioral development is unclear. This study aimed
      to determine if removal of testicular hormones during adolescence alters
      neurogenesis in the male rhesus macaque hippocampus. We used stereology to
      examine levels of cell proliferation, cell survival and neuronal differentiation
      in late adolescent male rhesus macaques (4.6-yrs old) that had previously been
      gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence
      of adolescent testicular hormones had no effect on cell proliferation, cell
      survival was increased by 65% and indices of immature neuronal differentiation
      were increased by 56% in gonadectomized monkeys compared to intact monkeys. We
      show for the first time that presence of circulating testicular hormones,
      including testosterone, may decrease neuronal survival in the primate hippocampus
      during adolescence. Our findings are in contrast to existing studies in adults
      where testosterone tends to be a pro-survival factor and demonstrate that
      testicular hormones may reduce hippocampal neurogenesis during the age typical of
      schizophrenia onset.

PMID- 24123730
TI  - Free-flow electrophoresis in proteome sample preparation.
AB  - An aim of proteome research is to identify the entire complement of proteins
      expressed in defined cell types of humans, animals, plants, and microorganisms.
      The approach requires searching for low abundant or even rarely expressed
      proteins in many cell types, as well as the determination of the protein
      expression levels in subcellular compartments and organelles. In recent years,
      rather powerful MS technologies have been developed. At this stage of MS device
      development, it is of highest interest to purify intact cell types or isolate
      subcellular compartments, where the proteins of interest are originating from,
      which determine the final composition of a peptide mixture. Free-flow
      electrophoresis proved to be useful to prepare meaningful peptide mixtures
      because of its improved capabilities in particle electrophoresis and the enhanced
      resolution in protein separation. Sample preparation by free-flow electrophoresis
      mediated particle separation was preferentially performed for purification of
      either organelles and their subspecies or major protein complexes. Especially,
      the introduction of isotachophoresis and interval zone electrophoresis improved
      the purity of the gained analytes of interest. In addition, free-flow IEF proved
      to be helpful, when proteins of low solubility, obtained, e.g. from cell
      membranes, were investigated. 

PMID- 24123731
TI  - Dimethyl adenosine transferase (KsgA) deficiency in Salmonella enterica Serovar
      Enteritidis confers susceptibility to high osmolarity and virulence attenuation
      in chickens.
AB  - Dimethyl adenosine transferase (KsgA) performs diverse roles in bacteria,
      including ribosomal maturation and DNA mismatch repair, and synthesis of KsgA is
      responsive to antibiotics and cold temperature. We previously showed that a ksgA
      mutation in Salmonella enterica serovar Enteritidis results in impaired
      invasiveness in human and avian epithelial cells. In this study, we tested the
      virulence of a ksgA mutant (the ksgA::Tn5 mutant) of S. Enteritidis in orally
      challenged 1-day-old chickens. The ksgA::Tn5 mutant showed significantly reduced
      intestinal colonization and organ invasiveness in chickens compared to those of
      the wild-type (WT) parent. Phenotype microarray (PM) was employed to compare the
      ksgA::Tn5 mutant and its isogenic wild-type strain for 920 phenotypes at 28
      degrees C, 37 degrees C, and 42 degrees C. At chicken body temperature (42
      degrees C), the ksgA::Tn5 mutant showed significantly reduced respiratory
      activity with respect to a number of carbon, nitrogen, phosphate, sulfur, and
      peptide nitrogen nutrients. The greatest differences were observed in the
      osmolyte panel at concentrations of >=6% NaCl at 37 degrees C and 42 degrees C.
      In contrast, no major differences were observed at 28 degrees C. In independent
      growth assays, the ksgA::Tn5 mutant displayed a severe growth defect in high
      osmolarity (6.5% NaCl) conditions in nutrient-rich (LB) and nutrient-limiting (M9
      minimum salts) media at 42 degrees C. Moreover, the ksgA::Tn5 mutant showed
      significantly reduced tolerance to oxidative stress, but its survival within
      macrophages was not impaired. Unlike Escherichia coli, the ksgA::Tn5 mutant did
      not display a cold-sensitivity phenotype; however, it showed resistance to
      kasugamycin and increased susceptibility to chloramphenicol. To the best of our
      knowledge, this is the first report showing the role of ksgA in S. Enteritidis
      virulence in chickens, tolerance to high osmolarity, and altered susceptibility
      to kasugamycin and chloramphenicol. 

PMID- 24123733
TI  - Laboratory evidence of norwalk virus contamination on the hands of infected
      individuals.
AB  - Human norovirus (NoV) outbreak investigations suggest that the hands of infected
      individuals play an important role in NoV transmission. However, there is no
      experimental evidence documenting the likelihood and degree of NoV contamination
      on hands. As part of a clinical trial designed to evaluate the efficacy of high
      pressure processing for Norwalk virus (NV) inactivation in oysters, 159 hand
      rinse samples were collected from 6 infected and 6 uninfected subjects. NV was
      concentrated from the samples by polyethylene glycol precipitation, followed by
      RNA extraction using an automated guanidinium isothiocyanate-silica method. NV
      RNA was detected and quantified using multiple NV-specific reverse transcription
      quantitative PCR (RT-qPCR) assays. A total of 25.4% (18/71) of the hand rinse
      samples collected from 6 infected volunteers were presumptively positive for NV,
      with an average of 3.86 log10 genomic equivalent copies (GEC) per hand. Dot blot
      hybridization of PCR products obtained using a different primer set, and DNA
      sequencing of selected amplicons, provided further confirmation of the presence
      of NV in the hand rinses. NV contamination was also detected in two hand rinse
      samples obtained from one uninfected subject. These findings provide definitive
      evidence of NV contamination on the hands of infected subjects observed under
      controlled clinical research conditions. Such data support the need for better
      hand hygiene strategies to prevent NoV transmission. 

PMID- 24123732
TI  - Aspergillus collagen-like genes (acl): identification, sequence polymorphism, and
      assessment for PCR-based pathogen detection.
AB  - The genus Aspergillus is a burden to public health due to its ubiquitous presence
      in the environment, its production of allergens, and wide demographic
      susceptibility among cystic fibrosis, asthmatic, and immunosuppressed patients.
      Current methods of detection of Aspergillus colonization and infection rely on
      lengthy morphological characterization or nonstandardized serological assays that
      are restricted to identifying a fungal etiology. Collagen-like genes have been
      shown to exhibit species-specific conservation across the noncollagenous regions
      as well as strain-specific polymorphism in the collagen-like regions. Here we
      assess the conserved region of the Aspergillus collagen-like (acl) genes and
      explore the application of PCR amplicon size-based discrimination among the five
      most common etiologic species of the Aspergillus genus, including Aspergillus
      fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus. Genetic polymorphism
      and phylogenetic analysis of the aclF1 gene were additionally examined among the
      available strains. Furthermore, the applicability of the PCR-based assay to
      identification of these five species in cultures derived from sputum and
      bronchoalveolar fluid from 19 clinical samples was explored. Application of
      capillary electrophoresis on nanogels was additionally demonstrated to improve
      the discrimination between Aspergillus species. Overall, this study demonstrated
      that Aspergillus acl genes could be used as PCR targets to discriminate between
      clinically relevant Aspergillus species. Future studies aim to utilize the
      detection of Aspergillus acl genes in PCR and microfluidic applications to
      determine the sensitivity and specificity for the identification of Aspergillus
      colonization and invasive aspergillosis in immunocompromised subjects. 

PMID- 24123734
TI  - Rapid detection and identification of nontuberculous mycobacterial pathogens in
      fish by using high-resolution melting analysis.
AB  - Mycobacterial infections in fish are commonly referred to as piscine
      mycobacteriosis, irrespectively of the specific identity of the causal organism.
      They usually cause a chronic disease and sometimes may result in high mortalities
      and severe economic losses. Nearly 20 species of Mycobacterium have been reported
      to infect fish. Among them, Mycobacterium marinum, M. fortuitum, and M. chelonae
      are generally considered the major agents responsible for fish mycobacteriosis.
      As no quick and inexpensive diagnostic test exists, we tested the potential of
      high-resolution melting analysis (HRMA) to rapidly identify and differentiate
      several Mycobacterium species involved in fish infections. By analyzing both the
      melting temperature and melting profile of the 16S-23S rRNA internal transcribed
      spacer (ITS), we were able to discriminate 12 different species simultaneously.
      Sensitivity tests conducted on purified M. marinum and M. fortuitum DNA revealed
      a limit of detection of 10 genome equivalents per reaction. The primers used in
      this procedure did not lead to any amplification signal with 16 control non
      Mycobacterium species, thereby demonstrating their specificity for the genus
      Mycobacterium. 

PMID- 24123735
TI  - Genetic diversity of newcastle disease virus in wild birds and pigeons in West
      Africa.
AB  - In West and Central Africa, virulent Newcastle disease virus (NDV) strains of the
      recently identified genotypes XIV, XVII, and XVIII are enzootic in poultry,
      representing a considerable threat to the sector. The increasing number of
      reports of virulent strains in wild birds at least in other parts of the world
      raised the question of a potential role of wild birds in the spread of virulent
      NDV in sub-Saharan Africa as well. We investigated 1,723 asymptomatic birds
      sampled at live-bird markets and sites important for wild-bird conservation in
      Nigeria and 19 sick or dead wild birds in Cote d'Ivoire for NDV class I and II.
      Typical avirulent wild-type genotype I strains were found in wild waterfowl in
      wetlands in northeastern Nigeria. They were unrelated to vaccine strains, and the
      involvement of inter- or intracontinental migratory birds in their circulation in
      the region is suggested. Phylogenetic analyses also revealed that genotype VI
      strains found in pigeons, including some putative new subgenotype VIh and VIi
      strains, were introduced on multiple separate occasions in Nigeria. A single
      virulent genotype XVIII strain was found in a dead wild bird in Cote d'Ivoire,
      probably as a result of spillover from sick poultry. In conclusion, screening of
      wild birds and pigeons for NDV revealed the presence a variety of virulent and
      avirulent strains in West Africa but did not provide strong evidence that wild
      birds play an important role in the spread of virulent strains in the region. 

PMID- 24123736
TI  - SdrA, a new DeoR family regulator involved in Streptomyces avermitilis
      morphological development and antibiotic production.
AB  - The SAV3339 (SdrA) protein of Streptomyces avermitilis, a member of the DeoR
      family of regulators, was assessed to determine its in vivo function by gene
      knockdown through the use of cis-encoded noncoding RNA and knockout of the sdrA
      gene. These analyses revealed that SdrA represents another class of Streptomyces
      regulator that controls morphological development and antibiotic production. 

PMID- 24123737
TI  - Bacteriophage orphan DNA methyltransferases: insights from their bacterial
      origin, function, and occurrence.
AB  - Type II DNA methyltransferases (MTases) are enzymes found ubiquitously in the
      prokaryotic world, where they play important roles in several cellular processes,
      such as host protection and epigenetic regulation. Three classes of type II
      MTases have been identified thus far in bacteria which function in transferring a
      methyl group from S-adenosyl-l-methionine (SAM) to a target nucleotide base,
      forming N-6-methyladenine (class I), N-4-methylcytosine (class II), or C-5
      methylcytosine (class III). Often, these MTases are associated with a cognate
      restriction endonuclease (REase) to form a restriction-modification (R-M) system
      protecting bacterial cells from invasion by foreign DNA. When MTases exist alone,
      which are then termed orphan MTases, they are believed to be mainly involved in
      regulatory activities in the bacterial cell. Genomes of various lytic and
      lysogenic phages have been shown to encode multi- and mono-specific orphan MTases
      that have the ability to confer protection from restriction endonucleases of
      their bacterial host(s). The ability of a phage to overcome R-M and other phage
      targeting resistance systems can be detrimental to particular biotechnological
      processes such as dairy fermentations. Conversely, as phages may also be
      beneficial in certain areas such as phage therapy, phages with additional
      resistance to host defenses may prolong the effectiveness of the therapy. This
      minireview will focus on bacteriophage-encoded MTases, their prevalence and
      diversity, as well as their potential origin and function. 

PMID- 24123738
TI  - The novel bacterial N-demethylase PdmAB is responsible for the initial step of
      N,N-dimethyl-substituted phenylurea herbicide degradation.
AB  - The environmental fate of phenylurea herbicides has received considerable
      attention in recent decades. The microbial metabolism of N,N-dimethyl-substituted
      phenylurea herbicides can generally be initiated by mono-N-demethylation. In this
      study, the molecular basis for this process was revealed. The pdmAB genes in
      Sphingobium sp. strain YBL2 were shown to be responsible for the initial mono-N
      demethylation of commonly used N,N-dimethyl-substituted phenylurea herbicides.
      PdmAB is the oxygenase component of a bacterial Rieske non-heme iron oxygenase
      (RO) system. The genes pdmAB, encoding the alpha subunit PdmA and the beta
      subunit PdmB, are organized in a transposable element flanked by two direct
      repeats of an insertion element resembling ISRh1. Furthermore, this transposable
      element is highly conserved among phenylurea herbicide-degrading sphingomonads
      originating from different areas of the world. However, there was no evidence of
      a gene for an electron carrier (a ferredoxin or a reductase) located in the
      immediate vicinity of pdmAB. Without its cognate electron transport components,
      expression of PdmAB in Escherichia coli, Pseudomonas putida, and other
      sphingomonads resulted in a functional enzyme. Moreover, coexpression of a
      putative [3Fe-4S]-type ferredoxin from Sphingomonas sp. strain RW1 greatly
      enhanced the catalytic activity of PdmAB in E. coli. These data suggested that
      PdmAB has a low specificity for electron transport components and that its
      optimal ferredoxin may be the [3Fe-4S] type. PdmA exhibited low homology to the
      alpha subunits of previously characterized ROs (less than 37% identity) and did
      not cluster with the RO group involved in O- or N-demethylation reactions,
      indicating that PdmAB is a distinct bacterial RO N-demethylase. 

PMID- 24123739
TI  - Evolved cobalamin-independent methionine synthase (MetE) improves the acetate and
      thermal tolerance of Escherichia coli.
AB  - Acetate-mediated growth inhibition of Escherichia coli has been found to be a
      consequence of the accumulation of homocysteine, the substrate of the cobalamin
      independent methionine synthase (MetE) that catalyzes the final step of
      methionine biosynthesis. To improve the acetate resistance of E. coli, we
      randomly mutated the MetE enzyme and isolated a mutant enzyme, designated MetE
      214 (V39A, R46C, T106I, and K713E), that conferred accelerated growth in the E.
      coli K-12 WE strain in the presence of acetate. Additionally, replacement of
      cysteine 645, which is a unique site of oxidation in the MetE protein, with
      alanine improved acetate tolerance, and introduction of the C645A mutation into
      the MetE-214 mutant enzyme resulted in the highest growth rate in acetate-treated
      E. coli cells among three mutant MetE proteins. E. coli WE strains harboring
      acetate-tolerant MetE mutants were less inhibited by homocysteine in l-isoleucine
      enriched medium. Furthermore, the acetate-tolerant MetE mutants stimulated the
      growth of the host strain at elevated temperatures (44 and 45 degrees C).
      Unexpectedly, the mutant MetE enzymes displayed a reduced melting temperature
      (Tm) but an enhanced in vivo stability. Thus, we demonstrate improved E. coli
      growth in the presence of acetate or at elevated temperatures solely due to
      mutations in the MetE enzyme. Furthermore, when an E. coli WE strain carrying the
      MetE mutant was combined with a previously found MetA (homoserine o
      succinyltransferase) mutant enzyme, the MetA/MetE strain was found to grow at 45
      degrees C, a nonpermissive growth temperature for E. coli in defined medium, with
      a similar growth rate as if it were supplemented by l-methionine. 

PMID- 24123740
TI  - Novel psychropiezophilic Oceanospirillales species Profundimonas piezophila gen.
      nov., sp. nov., isolated from the deep-sea environment of the Puerto Rico trench.
AB  - The diversity of deep-sea high-pressure-adapted (piezophilic) microbes in
      isolated monoculture remains low. In this study, a novel obligately
      psychropiezophilic bacterium was isolated from seawater collected from the Puerto
      Rico Trench at a depth of ~6,000 m. This isolate, designated YC-1, grew best in a
      nutrient-rich marine medium, with an optimal growth hydrostatic pressure of 50
      MPa (range, 20 to 70 MPa) at 8 degrees C. Under these conditions, the maximum
      growth rate was extremely slow, 0.017 h(-1), and the maximum yield was 3.51 *
      10(7) cells ml(-1). Cell size and shape changed with pressure, shifting from 4.0
      to 5.0 MUm in length and 0.5 to 0.8 MUm in width at 60 MPa to 0.8- to 1.0-MUm
      diameter coccoid cells under 20 MPa, the minimal pressure required for growth. YC
      1 is a Gram-negative, facultatively anaerobic heterotroph. Its predominant
      cellular fatty acids are the monounsaturated fatty acids (MUFAs) C16:1 and C18:1.
      Unlike many other psychropiezophiles, YC-1 does not synthesize any
      polyunsaturated fatty acids (PUFAs). Phylogenetic analysis placed YC-1 within the
      family of Oceanospirillaceae, closely related to the uncultured symbiont of the
      deep-sea whale bone-eating worms of the genus Osedax. In common with some other
      members of the Oceanospirillales, including those enriched during the Deepwater
      Horizon oil spill, YC-1 is capable of hydrocarbon utilization. On the basis of
      its characteristics, YC-1 appears to represent both a new genus and a new
      species, which we name Profundimonas piezophila gen. nov., sp. nov. 

PMID- 24123741
TI  - Feeding the probiotic Enterococcus faecium strain NCIMB 10415 to piglets
      specifically reduces the number of Escherichia coli pathotypes that adhere to the
      gut mucosa.
AB  - Feed supplementation with the probiotic Enterococcus faecium for piglets has been
      found to reduce pathogenic gut microorganisms. Since Escherichia coli is among
      the most important pathogens in pig production, we performed comprehensive
      analyses to gain further insight into the influence of E. faecium NCIMB 10415 on
      porcine intestinal E. coli. A total of 1,436 E. coli strains were isolated from
      three intestinal habitats (mucosa, digesta, and feces) of probiotic-supplemented
      and nonsupplemented (control) piglets. E. coli bacteria were characterized via
      pulsed-field gel electrophoresis (PFGE) for clonal analysis. The high diversity
      of E. coli was reflected by 168 clones. Multilocus sequence typing (MLST) was
      used to determine the phylogenetic backgrounds, revealing 79 sequence types
      (STs). Pathotypes of E. coli were further defined using multiplex PCR for
      virulence-associated genes. While these analyses discerned only a few significant
      differences in the E. coli population between the feeding groups, analyses
      distinguishing clones that were uniquely isolated in either the probiotic group
      only, the control group only, or both groups (shared group) revealed clear
      effects at the habitat level. Interestingly, extraintestinal pathogenic E. coli
      (ExPEC)-typical clones adhering to the mucosa were significantly reduced in the
      probiotic group. Our data show a minor influence of E. faecium on the overall
      population of E. coli in healthy piglets. In contrast, this probiotic has a
      profound effect on mucosa-adherent E. coli. This finding further substantiates a
      specific effect of E. faecium strain NCIMB 10415 in piglets against pathogenic E.
      coli in the intestine. In addition, these data question the relevance of data
      based on sampling fecal E. coli only. 

PMID- 24123742
TI  - A new synthetic route to N-benzyl carboxamides through the reverse reaction of N
      substituted formamide deformylase.
AB  - Previously, we isolated a new enzyme, N-substituted formamide deformylase, that
      catalyzes the hydrolysis of N-substituted formamide to the corresponding amine
      and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi,
      Proc. Natl. Acad. Sci. U. S. A. 101:13726-13731, 2004,
      doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the
      reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and
      formate. The reverse reaction proceeded only in the presence of high substrate
      concentrations. The effects of pH and inhibitors on the reverse reaction were
      almost the same as those on the forward reaction, suggesting that the forward and
      reverse reactions are both catalyzed at the same catalytic site. Bisubstrate
      kinetic analysis using formate and benzylamine and dead-end inhibition studies
      using a benzylamine analogue, aniline, revealed that the reverse reaction of this
      enzyme proceeds via an ordered two-substrate, two-product (bi-bi) mechanism in
      which formate binds first to the enzyme active site, followed by benzylamine
      binding and the subsequent release of NBFA. To our knowledge, this is the first
      report of the reverse reaction of an amine-forming deformylase. Surprisingly,
      analysis of the substrate specificity for acids demonstrated that not only
      formate, but also acetate and propionate (namely, acids with numbers of carbon
      atoms ranging from C1 to C3), were active as acid substrates for the reverse
      reaction. Through this reaction, N-substituted carboxamides, such as NBFA, N
      benzylacetamide, and N-benzylpropionamide, were synthesized from benzylamine and
      the corresponding acid substrates. 

PMID- 24123743
TI  - Characterization of bacteriophages Cp1 and Cp2, the strain-typing agents for
      Xanthomonas axonopodis pv. citri.
AB  - The strains of Xanthomonas axonopodis pv. citri, the causative agent of citrus
      canker, are historically classified based on bacteriophage (phage) sensitivity.
      Nearly all X. axonopodis pv. citri strains isolated from different regions in
      Japan are lysed by either phage Cp1 or Cp2; Cp1-sensitive (Cp1(s)) strains have
      been observed to be resistant to Cp2 (Cp2(r)) and vice versa. In this study,
      genomic and molecular characterization was performed for the typing agents Cp1
      and Cp2. Morphologically, Cp1 belongs to the Siphoviridae. Genomic analysis
      revealed that its genome comprises 43,870-bp double-stranded DNA (dsDNA), with 10
      bp 3'-extruding cohesive ends, and contains 48 open reading frames. The genomic
      organization was similar to that of Xanthomonas phage phiL7, but it lacked a
      group I intron in the DNA polymerase gene. Cp2 resembles morphologically
      Escherichia coli T7-like phages of Podoviridae. The 42,963-bp linear dsDNA genome
      of Cp2 contained terminal repeats. The Cp2 genomic sequence has 40 open reading
      frames, many of which did not show detectable homologs in the current databases.
      By proteomic analysis, a gene cluster encoding structural proteins corresponding
      to the class III module of T7-like phages was identified on the Cp2 genome.
      Therefore, Cp1 and Cp2 were found to belong to completely different virus groups.
      In addition, we found that Cp1 and Cp2 use different molecules on the host cell
      surface as phage receptors and that host selection of X. axonopodis pv. citri
      strains by Cp1 and Cp2 is not determined at the initial stage by binding to
      receptors. 

PMID- 24123744
TI  - A novel gene involved in the survival of Streptococcus mutans under stress
      conditions.
AB  - A Streptococcus mutans mutant defective in aciduricity was constructed by random
      insertion mutagenesis. Sequence analysis of the mutant revealed a mutation in
      gidA, which is known to be involved in tRNA modification in Streptococcus
      pyogenes. Complementation of gidA by S. pyogenes gidA recovered the acid
      tolerance of S. mutans. Although the gidA-inactivated S. pyogenes mutant
      exhibited significantly reduced expression of multiple extracellular virulence
      proteins, the S. mutans mutant did not. On the other hand, the gidA mutant of S.
      mutans showed reduced ability to withstand exposure to other stress conditions
      (high osmotic pressure, high temperature, and bacitracin stress) besides an
      acidic environment. In addition, loss of GidA decreased the capacity for glucose
      dependent biofilm formation by over 50%. This study revealed that gidA plays
      critical roles in the survival of S. mutans under stress conditions, including
      lower pH. 

PMID- 24123745
TI  - Interaction between the microbial community and invading Escherichia coli O157:H7
      in soils from vegetable fields.
AB  - The survival of Escherichia coli O157:H7 in soils can contaminate vegetables,
      fruits, drinking water, etc. However, data on the impact of E. coli O157:H7 on
      soil microbial communities are limited. In this study, we monitored the changes
      in the indigenous microbial community by using the phospholipid fatty acid (PLFA)
      method to investigate the interaction of the soil microbial community with E.
      coli O157:H7 in soils. Simple correlation analysis showed that the survival of E.
      coli O157:H7 in the test soils was negatively correlated with the ratio of Gram
      negative (G(-)) to Gram-positive (G(+)) bacterial PLFAs (G(-)/G(+) ratio). In
      particular, levels of 14 PLFAs were negatively correlated with the survival time
      of E. coli O157:H7. The contents of actinomycetous and fungal PLFAs in the test
      soils declined significantly (P, <0.05) after 25 days of incubation with E. coli
      O157:H7. The G(-)/G(+) ratio declined slightly, while the ratio of bacterial to
      fungal PLFAs (B/F ratio) and the ratio of normal saturated PLFAs to
      monounsaturated PLFAs (S/M ratio) increased, after E. coli O157:H7 inoculation.
      Principal component analysis results further indicated that invasion by E. coli
      O157:H7 had some effects on the soil microbial community. Our data revealed that
      the toxicity of E. coli O157:H7 presents not only in its pathogenicity but also
      in its effect on soil microecology. Hence, close attention should be paid to the
      survival of E. coli O157:H7 and its potential for contaminating soils. 

PMID- 24123746
TI  - Genomic overview and biological functions of exopolysaccharide biosynthesis in
      Bifidobacterium spp.
AB  - For many years, bacterial exopolysaccharides (EPS) have received considerable
      scientific attention, mainly due to their contribution to biofilm formation and,
      above all, because EPS are potential virulence factors. In recent times, interest
      in EPS research has enjoyed a welcome boost thanks to the discovery of their
      ability to mediate communication processes with their surrounding environment and
      to their contribution to host health maintenance. In this review, we provide a
      fresh perspective on the genetics and activity of these polymers in members of
      the Bifidobacterium genus, a common gut inhabitant of humans and animals that has
      been associated with several health-promoting effects. Bifidobacteria can use EPS
      to protect themselves against the harsh conditions of the gastrointestinal tract,
      thus improving their persistence in the host. Indeed, the relevant function of
      EPS for bifidobacteria is underlined by the fact that most genomes sequenced
      until now contain genes related to EPS biosynthesis. A high interspecies
      variability in the number of genes and structural organization is denoted among
      species/subspecies; thus, eps clusters in this genus do not display a consensus
      genetic architecture. Their different G+C content compared to that of the whole
      genome suggests that eps genes have been acquired by horizontal transfer. From
      the host perspective, EPS-producing bifidobacteria are able to trigger both
      innate and adaptive immune responses, and they are able to modulate the
      composition and activity of the gut microbiota. Thus, these polymers seem to be
      critical in understanding the physiology of bifidobacteria and their interaction
      with the host. 

PMID- 24123747
TI  - Preparation of sticky Escherichia coli through surface display of an adhesive
      catecholamine moiety.
AB  - Mussels attach to virtually all types of inorganic and organic surfaces in
      aqueous environments, and catecholamines composed of 3,4-dihydroxy-l
      phenylalanine (DOPA), lysine, and histidine in mussel adhesive proteins play a
      key role in the robust adhesion. DOPA is an unusual catecholic amino acid, and
      its side chain is called catechol. In this study, we displayed the adhesive
      moiety of DOPA-histidine on Escherichia coli surfaces using outer membrane
      protein W as an anchoring motif for the first time. Localization of
      catecholamines on the cell surface was confirmed by Western blot and
      immunofluorescence microscopy. Furthermore, cell-to-cell cohesion (i.e., cellular
      aggregation) induced by the displayed catecholamine and synthesis of gold
      nanoparticles on the cell surface support functional display of adhesive
      catecholamines. The engineered E. coli exhibited significant adhesion onto
      various material surfaces, including silica and glass microparticles, gold,
      titanium, silicon, poly(ethylene terephthalate), poly(urethane), and
      poly(dimethylsiloxane). The uniqueness of this approach utilizing the engineered
      sticky E. coli is that no chemistry for cell attachment are necessary, and the
      ability of spontaneous E. coli attachment allows one to immobilize the cells on
      challenging material surfaces such as synthetic polymers. Therefore, we envision
      that mussel-inspired catecholamine yielded sticky E. coli that can be used as a
      new type of engineered microbe for various emerging fields, such as whole living
      cell attachment on versatile material surfaces, cell-to-cell communication
      systems, and many others. 

PMID- 24123748
TI  - Establishing the yeast Kluyveromyces lactis as an expression host for production
      of the saposin-like domain of the aspartic protease cirsin.
AB  - Typical plant aspartic protease zymogens comprise a characteristic and plant
      specific insert (PSI). PSI domains can interact with membranes, and a role as a
      defensive weapon against pathogens has been proposed. However, the potential of
      PSIs as antimicrobial agents has not been fully investigated and explored yet due
      to problems in producing sufficient amounts of these domains in bacteria. Here,
      we report the development of an expression platform for the production of the PSI
      domain of cirsin in the generally regarded as safe (GRAS) yeast Kluyveromyces
      lactis. We successfully generated K. lactis transformants expressing and
      secreting significant amounts of correctly processed and glycosylated PSI, as
      well as its nonglycosylated mutant. A purification protocol with protein yields
      of ~4.0 mg/liter was established for both wild-type and nonglycosylated PSIs,
      which represents the highest reported yield for a nontagged PSI domain.
      Subsequent bioactivity assays targeting phytopathogenic fungi indicated that the
      PSI of cirsin is produced in a biologically active form in K. lactis and provided
      clear evidence for its antifungal activity. This yeast expression system thereby
      emerges as a promising production platform for further exploring the
      biotechnological potential of these plant saposin-like proteins. 

PMID- 24123750
TI  - A visible-light-mediated synthesis of carbazoles.

PMID- 24123749
TI  - Resistance of Bacillus subtilis spore DNA to lethal ionizing radiation damage
      relies primarily on spore core components and DNA repair, with minor effects of
      oxygen radical detoxification.
AB  - The roles of various core components, including alpha/beta/gamma-type small acid
      soluble spore proteins (SASP), dipicolinic acid (DPA), core water content, and
      DNA repair by apurinic/apyrimidinic (AP) endonucleases or nonhomologous end
      joining (NHEJ), in Bacillus subtilis spore resistance to different types of
      ionizing radiation including X rays, protons, and high-energy charged iron ions
      have been studied. Spores deficient in DNA repair by NHEJ or AP endonucleases,
      the oxidative stress response, or protection by major alpha/beta-type SASP, DPA,
      and decreased core water content were significantly more sensitive to ionizing
      radiation than wild-type spores, with highest sensitivity to high-energy-charged
      iron ions. DNA repair via NHEJ and AP endonucleases appears to be the most
      important mechanism for spore resistance to ionizing radiation, whereas oxygen
      radical detoxification via the MrgA-mediated oxidative stress response or KatX
      catalase activity plays only a very minor role. Synergistic radioprotective
      effects of alpha/beta-type but not gamma-type SASP were also identified,
      indicating that alpha/beta-type SASP's binding to spore DNA is important in
      preventing DNA damage due to reactive oxygen species generated by ionizing
      radiation. 

PMID- 24123751
TI  - Chiral phosphoric acid directed regioselective acetalization of carbohydrate
      derived 1,2-diols.
AB  - In control: A chiral phosphoric acid catalyst significantly enhances or
      completely overrides the inherent regioselective acetalization profiles exhibited
      by monosaccharide-derived 1,2-diol substrates. This study represents the first
      example of chiral-catalyst-directed regio- and enantioselective intermolecular
      acetalizations, which are complementary to existing methods for substrate
      controlled functionalization of polyols. 

PMID- 24123752
TI  - Cross-reactivity of cell-selective CRRETAWAC peptide with human and porcine
      endothelial cells.
AB  - We report on the cross-reactivity of the cell adhesive peptide CRRETAWAC between
      human and porcine endothelial cells (ECs). CRRETAWAC is a phage display derived
      peptide which has been shown to bind the alpha5 beta1 receptor on human ECs, but
      does not bind platelets and thus could be incorporated into a coating for
      cardiovascular biomaterials that resists platelet adhesion and thrombosis, while
      allowing for endothelialization. To determine the cross-reactivity of the
      peptide, attachment and growth of human and porcine ECs on CRRETAWAC
      fluorosurfactant polymer (FSP) coated surfaces was explored. CRRETAWAC FSP was
      synthesized and characterized by mass spectrometry, NMR, and IR spectroscopy. pEC
      attachment and growth on CRRETAWAC FSP was similar to the positive controls,
      human fibronectin and RGD FSP, achieving confluence in 72 h. Initial adhesion on
      CRRETAWAC FSP was also similar for porcine and human ECs. Blocking with soluble
      CRRETAWAC peptide reduced adhesion to CRRETAWAC coated surfaces by over 50%,
      indicating that the pECs specifically bind CRRETAWAC peptide. With this study, we
      have demonstrated that CRRETAWAC peptide coated surfaces are capable of binding
      porcine ECs in a specific manner and supporting a confluent layer of pECs. In
      vitro validation of the porcine model was critical for ensuring the best chance
      of success for the in vivo testing of CRRETAWAC coated ePTFE vascular grafts.

PMID- 24123753
TI  - Epigenetics, fragile X syndrome and transcriptional therapy.
AB  - Epigenetics refers to the study of heritable changes in gene expression that
      occur without a change in DNA sequence. Epigenetic mechanisms therefore include
      all transcriptional controls that determine how genes are expressed during
      development and differentiation, but also in individual cells responding to
      environmental stimuli. The purpose of this review is to examine the basic
      principles of epigenetic mechanisms and their contribution to human disorders
      with a particular focus on fragile X syndrome (FXS), the most common monogenic
      form of developmental cognitive impairment. FXS represents a prototype of the so
      called repeat expansion disorders due to "dynamic" mutations, namely the
      expansion (known as "full mutation") of a CGG repeat in the 5'UTR of the FMR1
      gene. This genetic anomaly is accompanied by epigenetic modifications (mainly DNA
      methylation and histone deacetylation), resulting in the inactivation of the FMR1
      gene. The presence of an intact FMR1 coding sequence allowed pharmacological
      reactivation of gene transcription, particularly through the use of the DNA
      demethylating agent 5'-aza-2'-deoxycytydine and/or inhibitors of histone
      deacetylases. These treatments suggested that DNA methylation is dominant over
      histone acetylation in silencing the FMR1 gene. The importance of DNA methylation
      in repressing FMR1 transcription is confirmed by the existence of rare unaffected
      males carrying unmethylated full mutations. Finally, we address the potential use
      of epigenetic approaches to targeted treatment of other genetic conditions.

PMID- 24123754
TI  - Rare complication of ventricular septal defect in three patients following
      transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is a highly-effective but
      technically challenging procedure. Despite improvement in device technology and
      operator techniques, complications are common and previously unknown procedural
      related complications continue to arise. In this report, we present a case series
      of three patients with acquired perimembranous ventricular septal defects
      following transfemoral TAVR with an Edwards SAPIEN prosthesis.

PMID- 24123755
TI  - Soluble CD23 measurement by CBA: A convenient and reliable quantification method
      in Chronic Lymphocytic Leukemia.
AB  - The soluble form of the transmembrane glycoprotein CD23 corresponding to the low
      affinity receptor for the immunoglobulin E (sCD23) is found in the serum of
      patients with chronic lymphocytic leukemia (CLL). In this disease, an increase in
      sCD23 level is predictive of poor prognosis at diagnosis as well as during
      clinical outcome. Quantification of sCD23 is classically performed by ELISA
      assay, a method not routinely used in hematology laboratories. Our aim was to
      apply cytometric bead array (CBA) technology to measure sCD23 levels. We tested
      420 serum samples, 360 from patients and 60 from healthy volunteers. We selected
      3 pairs of monoclonal antibodies (moAb) recognizing the CD23 molecule that were
      tested in various conditions of temperature, centrifugation, washing or chemical
      supplementation. Satisfactory performances in terms of repeatability (CV: 5%) and
      reproducibility (CV: 6%) were obtained with the selected pair of antibodies, with
      a threshold of positivity at 6 ng/mL. CBA and ELISA techniques were correlated
      with a Spearman coefficient at 0.99. The reproducibility and reliability of the
      sCD23 CBA assay were confirmed, with a Spearman coefficient at 0.99 in a series
      of 23 CLL patients and 13 controls tested in 2 laboratories equipped with
      different cytometers and using different lots of CBA reagents. Data obtained with
      serum and plasma samples were correlated with a Spearman coefficient at 0.99. Our
      study validates a simple method that allows the clinicians to benefit from an
      indicator of prognosis at the diagnosis as well as a marker of the evolution of
      CLL disease.

PMID- 24123756
TI  - Concise review: the immune status of mesenchymal stem cells and its relevance for
      therapeutic application.
AB  - Multipotentiality and anti-inflammatory activity, the two main properties of
      mesenchymal stem cells (MSCs), underlie their therapeutic prospective. During the
      past decade, numerous studies in animal models and clinical trials explored the
      potential of MSCs in the treatment of diseases associated with tissue
      regeneration and inflammatory control. Other qualities of MSCs: ready
      accessibility in bone marrow and fat tissue and rapid expansion in culture make
      the therapeutic use of patients' own cells feasible. The prevailing belief that
      MSCs are nonimmunogenic encouraged the use of unrelated donor cells in immune
      competent recipients. The data emerging from studies performed with immune
      incompatible cells in animal models for a wide-range of human diseases show,
      however, conflicting results and cast doubt on the immune privileged status of
      MSCs. Our analysis of the preclinical literature in this review is aimed to gain
      a better understanding of the therapeutic potential of immune-incompatible MSCs.
      Emphasis was laid on applications for enhancement of tissue repair in the absence
      of immune-suppressive therapy.

PMID- 24123757
TI  - Small-molecule mechanism of action studies in Caenorhabditis elegans.
AB  - A general protocol for exogenous small-molecule pull-down experiments with
      Caenorhabditis elegans is described; it provides a link between small-molecule
      screens in worms and existing mutant and RNAi technologies, thereby enabling
      organismal mechanism of action studies for the natural product clovanemagnolol.
      Forward chemical genetic screens followed by mechanism of action studies with C.
      elegans, when coupled with genetic validation of identified targets to reproduce
      the small molecule's phenotypic effects, provide a unique platform for
      discovering the biological targets of compounds that affect multicellular
      processes. First, the use of an immobilized FK506 derivative and soluble
      competition experiments with optimally prepared soluble C. elegans proteome
      successfully identified interactions with FK506 binding proteins 1 to 6. This
      approach was used to determine an unknown mechanism of action for
      clovanemagnolol, a small molecule that promotes axonal branching in both primary
      neuronal cultures and in vivo in C. elegans. Following the synthesis of an
      appropriately functionalized solid-phase reagent bearing a clovanemagnolol
      analogue pull-down experiments employing soluble competition identified kinesin
      light chain-1 (KLC-1), a protein involved in axonal cargo transport, as a
      putative target. This was corroborated through the use of mutant worms lacking
      klc-1 and possessing GFP neuronal labeling, reproducing the axonal branching
      phenotype induced by the small molecule clovanemagnolol. 

PMID- 24123759
TI  - 100th anniversary of Bohr's model of the atom.
AB  - In the fall of 1913 Niels Bohr formulated his atomic models at the age of 27.
      This Essay traces Bohr's fundamental reasoning regarding atomic structure and
      spectra, the periodic table of the elements, and chemical bonding. His enduring
      insights and superseded suppositions are also discussed. 

PMID- 24123760
TI  - Physiorack: an integrated MRI safe/conditional, gas delivery, respiratory gating,
      and subject monitoring solution for structural and functional assessments of
      pulmonary function.
AB  - PURPOSE: To evaluate the use of a modular MRI conditional respiratory monitoring
      and gating solution, designed to facilitate proper monitoring of subjects' vital
      signals and their respiratory efforts, during free-breathing and breathheld 19F,
      oxygen-enhanced, and Fourier-decomposition MRI-based acquisitions. MATERIALS AND
      METHODS: All Imaging was performed on a Siemens TIM Trio 3 Tesla MRI scanner,
      following Institutional Review Board approval. Gas delivery is accomplished
      through the use of an MR compatible pneumotachometer, in conjunction with two
      three-way pneumatically controlled Hans Rudolph Valves. The pneumatic valves are
      connected to Douglas bags used as the gas source. A mouthpiece (+nose clip) or an
      oro-nasal Hans Rudolph disposable mask is connected following the pneumatic valve
      to minimize dead-space and provide an airtight seal. Continuous
      monitoring/sampling of inspiratory and expiratory oxygen and carbon dioxide
      levels at the mouthpiece/mask is achieved through the use of an Oxigraf gas
      analyzer. RESULTS: Forty-four imaging sessions were successfully monitored,
      during Fourier-decomposition (n=3), fluorine-enhanced (n=29), oxygen-enhanced,
      and ultra short echo (n=12) acquisitions. The collected waveforms, facilitated
      proper monitoring and coaching of the subjects. CONCLUSION: We demonstrate an
      inexpensive, off-the-shelf solution for monitoring these signals, facilitating
      assessments of lung function. Monitoring of respiratory efforts and exhaled gas
      concentrations assists in understanding the heterogeneity of lung function
      visualized by gas imaging.

PMID- 24123761
TI  - ENU-3 functions in an UNC-6/netrin dependent pathway parallel to UNC
      40/DCC/frazzled for outgrowth and guidance of the touch receptor neurons in C.
      elegans.
AB  - BACKGROUND: UNC-6 and SLT-1 guide the migrations of the ventrally directed
      processes of the AVM and PVM touch receptor neurons and UNC-6 guides the axons of
      the DA and DB classes of motor neurons in C. elegans. The UNC-6 receptors are UNC
      5 and UNC-40. The axon outgrowth defects of a subset of the DB motor neurons in
      the absence of UNC-5 are enhanced by mutations in enu-3. RESULTS: An enu-3
      mutation enhances defects in ventral guidance of the processes of the AVM and PVM
      touch receptor neurons, the dorsal guidance of the distal tip cell and causes
      additional architectural defects in axons in unc-40 mutant strains in an UNC-6
      dependent manner. These observations suggest that ENU-3 and UNC-40 function in
      parallel pathways dependent on UNC-6. ENU-3 depends on the presence of UNC-40 for
      its full effect on motor neuron axon outgrowth. CONCLUSIONS: ENU-3 works in an
      UNC-6 dependent pathway parallel to UNC-40 in ventral guidance of AVM and PVM and
      in dorsal guidance of the distal tip cells. Motor neuron axon outgrowth defects
      are caused by the presence of UNC-40 and the absence of functional UNC-5 or UNC-6
      and defects are enhanced by the absence of functional ENU-3.

PMID- 24123763
TI  - John Cairns, Jr - an appreciation of his life and contributions.

PMID- 24123762
TI  - Health and well-being in adolescent survivors of early childhood cancer: a report
      from the Childhood Cancer Survivor Study.
AB  - OBJECTIVE: With the growing number of childhood cancer survivors in the US, it is
      important to assess the well-being of these individuals, particularly during the
      transitional phase of adolescence. Data about adolescent survivors' overall
      health and quality of life will help identify survivor subgroups most in need of
      targeted attention to successfully transition to adulthood. PARTICIPANTS AND
      METHODS: This ancillary study to the Childhood Cancer Survivor Study focused on
      children 15-19 years of age who had been diagnosed with cancer before the age of
      4 years. A cohort of siblings of pediatric cancer survivors of the same ages
      served as a comparison sample. Adolescent health was assessed using the Child
      Health and Illness Profile-Adolescent Edition (CHIP-AE) survey. RESULTS: The teen
      survey was sent to 444 survivor teens and 189 siblings. Of these, 307(69%)
      survivors and 97 (51%) siblings completed and returned the survey. The overall
      health profiles of siblings and survivors were similar. Among survivors, females
      scored significantly below males on satisfaction, discomfort, and disorders
      domains. Survivors diagnosed with central nervous system tumors scored less
      favorably than leukemia survivors in the global domains of satisfaction and
      disorders. CONCLUSION: In general, adolescent survivors fare favorably compared
      to healthy siblings. However, identification of the subset of pediatric cancer
      survivors who are more vulnerable to medical and psychosocial disorders in
      adolescence provides the opportunity for design and implementation of
      intervention strategies that may improve quality of life.

PMID- 24123770
TI  - Study on cervical muscle volume by means of three-dimensional reconstruction.
AB  - PURPOSE: To quantify the cervical muscle volume variation by means of three
      dimensional reconstruction from MRI images. MATERIALS AND METHODS: Sixteen
      subjects were scanned using a Philips MRI scanner, including 11 men and 5 women,
      aged from 23 to 33 years, weighting between 49-80 kg. The deformation of a
      parametric specific object method was used to develop three-dimensional muscle
      models from contours on a small number of MRI images. Six subjects were
      reconstructed by two observers for evaluating the reliability by means of
      intraclass correlation coefficient (ICC). The results were also compared with in
      vivo measurement on a single specimen from a reference literature. The difference
      in left and right muscles volumes was assessed with a paired Wilcoxon signed rank
      test. RESULTS: The results showed good reliability by means of ICC study and were
      consistent with the in vivo specimen measurements. The left and right paired
      muscle volumes showed no significant difference. Interindividual variance was
      large that could reach 364 cm(3) , but the ratio of a given muscle volume to the
      total volume was less variable, always lower than 13%. The maximum cross
      sectional areas of cervical muscles varied greatly between individuals and the
      maximum values were mostly found at the C6-C7 level. CONCLUSION: This study
      provides initial results which could be used as reference data for clinical
      evaluation and biomechanical model development.

PMID- 24123771
TI  - Development of interspecies nuclear transfer embryos reconstructed with argali
      (Ovis ammon) somatic cells and sheep ooplasm.
AB  - Interspecies nuclear transfer has already achieved success in several species,
      which shows great potential in recovery and conservation of endangered animals.
      The study was conducted to establish an efficient system for in vitro argali
      (Ovis ammon)-sheep embryo reconstruction via interspecies somatic cell nuclear
      transfer (iSCNT). The competence of domestic sheep cytoplasts to reprogram the
      adult argali fibroblast nuclei was evaluated, and the effects of enucleation
      methods and donor cell passage and cell state on the in vitro development of
      argali-sheep cloned embryos were also examined. Sheep oocytes could support
      argali and sheep fibroblast cell nuclei transfer and develop to blastocysts in
      vitro. Oocytes matured for 21-23 h and enucleated by chemically assisted
      enucleation (CAE) had a higher enucleation rate than blind enucleation (BE), but
      the development rate of iSCNTembryos was the same (P>0.05). Moreover, passage
      numbers of fibroblast cells <10, as well as the cell cycle stages did not affect
      the development rate of iSCNT reconstructed embryos. Thus sheep cytoplasm
      successfully supports argali nucleus development to blastocyst stage after
      optimising the nuclear transfer procedure, which indicates that iSCNT can be used
      to conserve endangered argali in the near future.

PMID- 24123772
TI  - Cystic fibrosis transmembrane conductance regulator-mRNA delivery: a novel
      alternative for cystic fibrosis gene therapy.
AB  - BACKGROUND: Cystic fibrosis (CF) is the most frequent lethal genetic disease in
      the Caucasian population. CF is caused by a defective gene coding for the cystic
      fibrosis transmembrane conductance regulator (CFTR), a cAMP- and ATP-dependent
      Cl(-) channel and central regulatory protein in epithelia. CFTR influences the
      fluid composition of the mucus in the respiratory tract. The most common mutation
      inducing CF, DeltaF508, impairs CFTR processing within the cell and thus prevents
      functional CFTR expression in the apical membrane. The present study aimed to
      investigate the functional restoration of CFTR in human CF airway epithelia after
      transfection with optimized wild-type (wt)CFTR-mRNA. METHODS: We used primary
      cultured human nasal epithelial (HNE) cells and the human bronchial epithelial
      cell line CFBE41o(-) that stably expresses DeltaF508-CFTR and carried out
      transepithelial Ussing chamber measurements after transfection with optimized
      wtCFTR-mRNA. We confirmed the data obtained using immunofluorescence and protein
      biochemical approaches. RESULTS: Transfection of the CFBE41o(-) cells with wtCFTR
      mRNA restored cAMP-induced CFTR currents similar to the values seen in control
      cells (16HBE14o(-)). Using immunofluorescence approaches, we demonstrated that a
      considerable amount of CFTR is located at the apical surface in the CF cells
      after transfection. Western blot analyses of wtCFTR-mRNA transfected CFBE41o(-)
      cells confirmed these findings. Furthermore, we demonstrated physiological
      relevance by using primary cultured HNE cells and showed an almost two-fold
      increase in the cAMP-stimulated CFTR current after transfection. CONCLUSIONS:
      From these data, we conclude that CFTR-mRNA transfection could comprise a novel
      alternative for gene therapy to restore impaired CFTR function.

PMID- 24123774
TI  - Synthesis of SiO2 and CaO rich calcium silicate systems via sol-gel process:
      bioactivity, biocompatibility, and drug delivery tests.
AB  - Silica and calcium silicate amorphous materials, mixed with sodium ampicillin, a
      broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous
      nature of the gels was ascertained by X-ray diffraction analysis. The bioactivity
      of the synthesized materials has been put into evidence by the appearance of a
      crystal of hydroxyapatite on the surface of the samples soaked in a fluid
      simulating the composition of the human blood plasma, as detected through FTIR
      measurements and SEM micrographs. The present work refers to a series of in-vitro
      biocompatibility tests, which has been performed on silicate and CaO rich calcium
      silicate gel-glasses, to study the cell behavior when seeded on 1 cm(2) material
      fragments, introduced into an in-vitro culture system. 3T3 cell lines have been
      used and the viability has been evaluated by WST-8 test. The composition of the
      adopted glasses can be expressed by the following general formula: x CaO* (1 - x)
      SiO2 with x = 0.00; 0.30; 0.40; 0.50; 0.60. Subsequently, release kinetics in a
      simulate body fluid (SBF) has been investigated. The amount of sodium ampicillin
      released has been detected by UV-Vis spectroscopy. The release kinetics has
      appeared to occur in more than one stage. All data have shown that those
      materials could be used as drug delivery bioactive systems.

PMID- 24123773
TI  - A specific inhibitor of PfCDPK4 blocks malaria transmission: chemical-genetic
      validation.
AB  - Malaria parasites are transmitted by mosquitoes, and blocking parasite
      transmission is critical in reducing or eliminating malaria in endemic regions.
      Here, we report the pharmacological characterization of a new class of malaria
      transmission-blocking compounds that acts via the inhibition of Plasmodia CDPK4
      enzyme. We demonstrate that these compounds achieved selectivity over mammalian
      kinases by capitalizing on a small serine gatekeeper residue in the active site
      of the Plasmodium CDPK4 enzyme. To directly confirm the mechanism of action of
      these compounds, we generated P. falciparum parasites that express a drug
      resistant methionine gatekeeper (S147 M) CDPK4 mutant. Mutant parasites showed a
      shift in exflagellation EC50 relative to the wild-type strains in the presence of
      compound 1294, providing chemical-genetic evidence that CDPK4 is the target of
      the compound. Pharmacokinetic analyses suggest that coformulation of this
      transmission-blocking agent with asexual stage antimalarials such as artemisinin
      combination therapy (ACT) is a promising option for drug delivery that may reduce
      transmission of malaria including drug-resistant strains. Ongoing studies include
      refining the compounds to improve efficacy and toxicological properties for
      efficient blocking of malaria transmission.

PMID- 24123775
TI  - Establishment and assessment of a new human embryonic stem cell-based biomarker
      assay for developmental toxicity screening.
AB  - A metabolic biomarker-based in vitro assay utilizing human embryonic stem (hES)
      cells was developed to identify the concentration of test compounds that perturbs
      cellular metabolism in a manner indicative of teratogenicity. This assay is
      designed to aid the early discovery-phase detection of potential human
      developmental toxicants. In this study, metabolomic data from hES cell culture
      media were used to assess potential biomarkers for development of a rapid in
      vitro teratogenicity assay. hES cells were treated with pharmaceuticals of known
      human teratogenicity at a concentration equivalent to their published human peak
      therapeutic plasma concentration. Two metabolite biomarkers (ornithine and
      cystine) were identified as indicators of developmental toxicity. A targeted
      exposure-based biomarker assay using these metabolites, along with a cytotoxicity
      endpoint, was then developed using a 9-point dose-response curve. The
      predictivity of the new assay was evaluated using a separate set of test
      compounds. To illustrate how the assay could be applied to compounds of unknown
      potential for developmental toxicity, an additional 10 compounds were evaluated
      that do not have data on human exposure during pregnancy, but have shown positive
      results in animal developmental toxicity studies. The new assay identified the
      potential developmental toxicants in the test set with 77% accuracy (57%
      sensitivity, 100% specificity). The assay had a high concordance (>=75%) with
      existing in vivo models, demonstrating that the new assay can predict the
      developmental toxicity potential of new compounds as part of discovery phase
      testing and provide a signal as to the likely outcome of required in vivo tests. 

PMID- 24123776
TI  - Sensenbrenner syndrome (Cranioectodermal dysplasia): clinical and molecular
      analyses of 39 patients including two new patients.
AB  - Sensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare
      multiple anomaly syndrome with distinctive craniofacial appearance, skeletal,
      ectodermal, connective tissue, renal, and liver anomalies. Dramatic advances with
      next-generation sequencing have expanded its phenotypic variability and molecular
      heterogeneity. We review 39 patients including two new patients, one with
      compound heterozygous novel mutations in WDR35 and a previously unreported
      multisutural craniosynostosis that may be a part of Sensenbrenner syndrome. In 14
      of 25 (56.0%) patients pathogenic mutations have been identified in 4 different
      genes that regulate (intraflagellar) cilia transport. We compared Sensenbrenner
      syndrome to asphyxiating thoracic dystrophy-Jeune syndrome (ATD-JS) and other
      ciliopathies. Our analyses showed that the high anterior hairline, forehead
      bossing and dolichocephaly (accompanied by sagittal craniosynostosis in more than
      half of the patients) occur in almost all patients with Sensenbrenner syndrome.
      Metaphyseal dysplasia with narrow thorax, proximal limb shortness, and short
      fingers are typical of Sensenbrenner syndrome and ATD-JS. Respiratory
      complications have been reported in both syndromes, usually less severe with
      Sensenbrenner syndrome. Proposed diagnostic criteria for Sensenbrenner syndrome
      include the distinctive craniofacial appearance, ubiquitous brachydactyly and
      ectodermal anomalies, and sagittal craniosynostosis. Mild heart defects have been
      noted, but there have been no atrioventricular canal or heterotaxy defects that
      are common in Ellis-Van Creveld syndrome. We anticipate that the steady
      identification of molecularly defined patients may allow correlation of phenotype
      and genotype. Additional natural history data will improve genetic counseling and
      current guidelines.

PMID- 24123777
TI  - The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.),
      on colon carcinogenesis is related to antiproliferative and proapoptotic effects.
AB  - SCOPE: Colorectal cancer is an important health problem across the world. Here,
      we investigated the possible antiproliferative/proapoptotic effects of bromelain
      (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human
      colorectal carcinoma cell line and its potential chemopreventive effect in a
      murine model of colon cancer. METHODS AND RESULTS: Proliferation and apoptosis
      were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H
      thymidine incorporation assay and caspase 3/7 activity measurement, respectively.
      Extracellular signal-related kinase (ERK) and Akt expression were evaluated by
      Western blot analysis, reactive oxygen species production by a fluorimetric
      method. In vivo, bromelain was evaluated using the azoxymethane murine model of
      colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis
      in Caco-2 cells. The effect of bromelain was associated to downregulation of
      pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive
      oxygen species production. In vivo, bromelain reduced the development of aberrant
      crypt foci, polyps, and tumors induced by azoxymethane. CONCLUSION: Bromelain
      exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells
      and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing
      foods and/or bromelain itself may represent good candidates for colorectal cancer
      chemoprevention.

PMID- 24123778
TI  - Surface modifications of influenza proteins upon virus inactivation by beta
      propiolactone.
AB  - Inactivation of intact influenza viruses using formaldehyde or beta-propiolactone
      (BPL) is essential for vaccine production and safety. The extent of chemical
      modifications of such reagents on viral proteins needs to be extensively
      investigated to better control the reactions and quality of vaccines. We have
      evaluated the effect of BPL inactivation on two candidate re-assortant vaccines
      (NIBRG-121xp and NYMC-X181A) derived from A/California/07/2009 pandemic influenza
      viruses using high-resolution FT-ICR MS-based proteomic approaches. We report
      here an ultra performance LC MS/MS method for determining full-length protein
      sequences of hemagglutinin and neuraminidase through protein delipidation,
      various enzymatic digestions, and subsequent mass spectrometric analyses of the
      proteolytic peptides. We also demonstrate the ability to reliably identify
      hundreds of unique sites modified by propiolactone on the surface of glycoprotein
      antigens. The location of these modifications correlated with changes to protein
      folding, conformation, and stability, but demonstrated no effect on protein
      disulfide linkages. In some cases, these modifications resulted in suppression of
      protein function, an effect that correlated with the degree of change of the
      modified amino acids' side chain length and polarity. 

PMID- 24123779
TI  - Preparation and in vitro characterization of biomorphic silk fibroin scaffolds
      for bone tissue engineering.
AB  - In bone tissue engineering, a qualified scaffold should provide a three
      dimensional porous structure mimicking the extracellular matrix of bone except
      good biological properties. In this study, biomorphic silk fibroin (SF) scaffolds
      were fabricated from cane by an innovative biotemplating-negative mold process.
      The physicochemical properties, in vitro enzymatic degradation behavior and
      biocompatibility of the biomorphic SF scaffolds were investigated. The results
      showed that the scaffolds well inherited the original porous morphology of cane,
      and possessed good mechanical stability. The scaffolds had a compressive modulus
      of 1.56 +/- 0.08 MPa and a porosity of 82.73%, and exhibited a bimodal pore size
      distribution (15 and 172 MUm). The degradation ratio of the SF scaffolds
      increased with prolonging degradation time and reached 29% within 21 days when
      exposed to 1.0 U/mL collagenase IA. The in vitro cytocompatibility evaluation
      indicated that the scaffolds could support cell attachment, proliferation, and
      osteogenic differentiation of osteoblast-like MC3T3-E1 cells, as assessed by SEM,
      fluorescent staining, MTT, and ALP activity assays. The results indicated the
      potential of biomorphic SF scaffolds for bone tissue engineering.

PMID- 24123780
TI  - Substance abuse treatment and its association with relapse to alcohol use after
      liver transplantation.
AB  - Many liver transplantation (LT) programs require substance abuse (SA) treatment
      for candidates with a history of alcohol abuse. However, there are no data
      indicating that SA treatment prevents post-LT alcohol relapse. We examined 118
      adults who underwent LT from May 2002 to February 2011 to explore the
      relationship between SA treatment and post-LT relapse to any alcohol use. Sixty
      one patients (52%) with a history of alcohol abuse or dependence received SA
      treatment before LT. Relapse to any alcohol use was identified in 40 LT
      recipients (34%). Patients who received SA treatment before LT did not differ
      significantly in the rate of post-LT alcohol relapse from patients who did not
      receive treatment before transplantation(30% versus 39%, P = 0.20). However,
      patients who received SA treatment both before and after transplantation had
      significantly lower rates of alcohol relapse (16%) than patients who received no
      SA treatment (41%) or SA treatment only before LT (45%, P = 0.03). Our findings
      suggest that LT programs should consider placing more emphasis on the
      continuation of some type of SA treatment after transplantation. Future research
      should prospectively examine the optimal timing for SA treatment that will
      attenuate the risk of alcohol relapse after transplantation.

PMID- 24123781
TI  - Best practices for transradial angiography and intervention: a consensus
      statement from the society for cardiovascular angiography and intervention's
      transradial working group.

PMID- 24123782
TI  - Enriched environment increases neurogenesis and improves social memory
      persistence in socially isolated adult mice.
AB  - Social memory consists of the information necessary to identify and recognize
      cospecifics and is essential to many forms of social interaction. Social memory
      persistence is strongly modulated by the animal's experiences. We have shown in
      previous studies that social isolation (SI) in adulthood impairs social memory
      persistence and that an enriched environment (EE) prevents this impairment.
      However, the mechanisms involved in the effects of SI and EE on social memory
      persistence remain unknown. We hypothesized that the mechanism by which SI and EE
      affect social memory persistence is through their modulation of neurogenesis. To
      investigate this hypothesis, adult mice were submitted to 7 days of one of the
      following conditions: group-housing in a standard (GH) or enriched environment
      (GH+EE); social isolation in standard (SI) or enriched environment (SI+EE). We
      observed an increase in the number of newborn neurons in the dentate gyrus of the
      hippocampus (DG) and glomerular layer of the olfactory bulb (OB) in both GH+EE
      and SI+EE mice. However, this increase of newborn neurons in the granule cell
      layer of the OB was restricted to the GH+EE group. Furthermore, both SI and SI+EE
      groups showed less neurogenesis in the mitral layer of the OB. Interestingly, the
      performance of the SI mice in the buried food-finding task was inferior to that
      of the GH mice. To further analyze whether increased neurogenesis is in fact the
      mechanism by which the EE improves social memory persistence in SI mice, we
      administered the mitotic inhibitor AraC or saline directly into the lateral
      ventricles of the SI+EE mice. We found that the AraC treatment decreased cell
      proliferation in both the DG and OB, and impaired social memory persistence in
      the SI+EE mice. Taken together, our results strongly suggest that neurogenesis is
      what supports social memory persistence in socially isolated mice.

PMID- 24123783
TI  - PEGylation and zwitterionization: pros and cons in the renal clearance and tumor
      targeting of near-IR-emitting gold nanoparticles.

PMID- 24123784
TI  - Physical activity and psychological health in breast cancer survivors: an
      application of basic psychological needs theory.
AB  - OBJECTIVE: The role of psychological need satisfaction in terms of understanding
      the mechanisms through which leisure-time physical activity (LTPA) is associated
      with psychological health in breast cancer survivors who have recently completed
      treatment was examined. METHODS: Adopting a longitudinal two-wave design, female
      breast cancer survivors (N = 144) completed self-report instruments of LTPA,
      psychological need satisfaction, and psychological health at two points separated
      by 3 months. The first test administration period was 6 months following the
      completion of primary treatment. RESULTS: Change score analyses demonstrated that
      greater LTPA across the 3-month period was associated with greater perceptions of
      well-being (rs ranged from .17 to .20) and lower ill-being (rs ranged from -.06
      to -.21). Results of multiple mediation analyses demonstrated that psychological
      need fulfillment underpinned the LTPA-well-being relationship only. CONCLUSIONS:
      Collectively these findings indicate that increased engagement in LTPA represents
      one factor associated with greater psychological health in breast cancer
      survivors, with fulfilling the psychological need for relatedness most salient in
      understanding this relationship. Continued investigation into the mechanisms
      associated with reductions in ill-being in breast cancer survivors appear
      justified.

PMID- 24123785
TI  - Loss of spastin function results in disease-specific axonal defects in human
      pluripotent stem cell-based models of hereditary spastic paraplegia.
AB  - Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate
      disease-specific axonal pathology hold the key to understanding why certain axons
      degenerate in patients and to developing therapies. SPG4, the most common form of
      HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes
      the microtubule-severing ATPase spastin. Here, we have generated a human neuronal
      model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4
      patient and differentiating these cells into telencephalic glutamatergic neurons.
      The SPG4 neurons displayed a significant increase in axonal swellings, which
      stained strongly for mitochondria and tau, indicating the accumulation of axonal
      transport cargoes. In addition, mitochondrial transport was decreased in SPG4
      neurons, revealing that these patient iPSC-derived neurons recapitulate disease
      specific axonal phenotypes. Interestingly, spastin protein levels were
      significantly decreased in SPG4 neurons, supporting a haploinsufficiency
      mechanism. Furthermore, cortical neurons derived from spastin-knockdown human
      embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that
      the axonal defects can be caused by loss of spastin function. These spastin
      knockdown hESCs serve as an additional model for studying HSP. Finally, levels of
      stabilized acetylated-tubulin were significantly increased in SPG4 neurons.
      Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling
      phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs.
      Thus, this study demonstrates the successful establishment of human pluripotent
      stem cell-based neuronal models of SPG4, which will be valuable for dissecting
      the pathogenic cellular mechanisms and screening compounds to rescue the axonal
      degeneration in HSP.

PMID- 24123786
TI  - Assessment of sleep and circadian rhythm disorders in the very old: the Newcastle
      85+ Cohort Study.
AB  - OBJECTIVES: to examine the association between subjective and objective measures
      of sleep and wake and other health parameters in a cohort of the very old.
      DESIGN: a population-based cohort study. SETTING: primary care, North East
      England. PARTICIPANTS: four hundred and twenty-one men and women, aged 87-89,
      recruited to the Newcastle 85+ Study cohort. METHODS: sleep questionnaires were
      administered and sleep-wake patterns were assessed over 5-7 days with a novel
      wrist triaxial accelerometer. Associations between sleep measures and various
      health parameters, including mortality at 24 months, were examined. RESULTS: only
      16% of participants perceived their sleep as severely disturbed as assessed with
      questionnaire responses. Wrist accelerometry showed marked variation between
      normal and abnormal sleep-wake cycles that did not correlate with the
      participants' perception of sleep. Impaired sleep-wake cycles were significantly
      associated with cognitive impairment, disability, depression, increased falls,
      body mass index and arthritis but not with any other specific disease markers and
      with decreased survival. CONCLUSIONS: commonly used sleep questionnaires do not
      differentiate well between those with objectively determined disturbance of sleep
      wake cycles and those with normal cycles. Abnormal sleep-wake patterns are
      associated with institutionalisation, cognitive impairment, disability,
      depression and arthritis but not with other diseases; there is also an
      association with reduced survival.

PMID- 24123787
TI  - Tailored glycopolymers as anticoagulant heparin mimetics.

PMID- 24123788
TI  - Improved anatomical reproducibility in quantitative lower-limb muscle MRI.
AB  - PURPOSE: To compare the influence of two limb positions and slice prescription
      using scout-image-based and surface-anatomy-based methods on the reproducibility
      of quantitative MRI of lower-limb muscles. MATERIALS AND METHODS: Ten healthy
      subjects were scanned at 3 Tesla with a two-dimensional turbo spin-echo T1
      weighted acquisition. Imaging was performed at thigh and calf level in two
      subject limb positions and independently repeated by a second operator. Regions
      of-interest (ROI) were drawn on three muscles at thigh and calf levels on axial
      slices at fixed distance from the knee joint and at a level determined by surface
      anatomy. RESULTS: Test-retest reliability of muscle cross-sectional area and ROI
      area overlap were similar for both limb positioning methods. Changing limb
      position between scans reduced ROI overlap (P < 0.01). Scout-image-based slice
      prescription resulted in narrower limits of agreement and higher intraclass
      correlation coefficients compared with surface-anatomy-based slice prescription.
      CONCLUSION: Slice prescription based on fixed distance from the knee joint
      provided superior reproducibility of slice location than a surface anatomy-based
      method and should be used for longitudinal quantitative MRI studies. Exact
      subject positioning will depend on scanner and coil configuration, but should be
      consistent through a longitudinal study.

PMID- 24123789
TI  - Islet transplantation in type 1 diabetes: hype, hope and reality - a clinician's
      perspective.
AB  - The beta-cell replacement by islet transplantation is an attractive approach for
      normalizing blood glucose without hypoglycaemia in patient with type 1 diabetes
      mellitus (T1D). A pioneer study by the Edmonton group more than a decade ago
      showed that alloislet transplantation may result in insulin independence for at
      least 1 year after transplantation. This breakthrough excited researchers,
      physicians and patients, who felt that the ultimate goal of cure for T1D was at
      hand. Longer follow-up of patients who underwent islet transplantation showed
      less favourable results, with only approximately 10% of the patients remaining
      insulin-free 5 years after transplantation. In the last few years, progress has
      been made, and the success rate of islet transplantation has steadily increased.
      Important hurdles, however, related to limited tissue supply and need for life
      long immunosuppressive drugs have yet to be overcome. Herein, we review recent
      achievements in islet transplantation and the challenges that still need to be
      addressed before this procedure can become a standard therapy for T1D.

PMID- 24123790
TI  - Female donor to male recipient gender discordance results in inferior graft
      survival: a prospective study of 1,042 liver transplants.
AB  - BACKGROUND: The influence of donor-recipient gender mismatch on outcomes after
      liver transplantation (LT) is controversial. The aim of this study was to
      evaluate the effect of donor and recipient gender discordance on graft survival.
      METHODS: All patients who underwent primary LT from 1994-2012 at a single-center
      were identified prospectively. Clinico-demographic data were collected at the
      time of LT and last follow-up. Gender match included both male donor to male
      recipient (MM) and female donor to female recipient (FF), while gender mismatch
      included female donor to male recipient (FM) and male donor to female recipient
      (MF). Survival curves for graft survival were generated using Kaplan-Meier method
      and compared by log-rank test. Unadjusted and multivariate adjusted COX
      regression analyzing graft survival at up to 10 years post-transplant was
      performed. RESULTS: A total of 1,042 subjects fulfilled the criteria. Graft
      survival in patients receiving a donor-recipient gender match was better than
      those receiving a gender mismatch (P = 0.047). Female-to-male transplants had the
      worst graft survival of all combinations (P < 0.001); this difference was
      maintained in multivariate regression after adjustment for recipient and donor
      variables (hazards ratio 2.09, P = 0.013). CONCLUSION: Female-to-male liver
      transplants are associated with a statistically significant poorer graft survival
      as compared with other donor-recipient gender groups.

PMID- 24123791
TI  - Evaluation of a bioactive bone-inducing material consisting of collagen scaffolds
      and collagen-binding bone morphogenetic protein 2.
AB  - Bioactive bone-inducing material (BBIM) is a collagen-based scaffold composed of
      demineralized bone matrix and collagen-binding domain bone morphogenetic protein
      2 (BMP-2). BBIM is regarded as a promising bone-inducing scaffold to repair bone
      defects. In this work, we evaluated the biocompatibility and osteogenecity of
      BBIM. Using enzyme-linked immunosorbent assay, the level of BMP-2 on BBIM was
      detected and considered adequate. Kunming mice were used as the animal model to
      investigate the acute systemic toxicity, long-term bone regeneration, ectopic
      bone formation, and chronic systemic toxicity. Results show that BBIM induced no
      serious inflammatory reaction or acute and chronic systemic toxicity. Our
      analyses also demonstrated significant homogeneous ectopic bone formation as well
      as significantly high numbers of erythrocytes in the BBIM groups in the chronic
      systemic toxicity study, a phenomenon which may provide indirect proof of the
      bone regeneration capacity of BBIM, which may be considered as a bioactivity
      indicator in future studies.

PMID- 24123792
TI  - A post-hoc comparison of the utility of sanger sequencing and exome sequencing
      for the diagnosis of heterogeneous diseases.
AB  - The advent of massive parallel sequencing is rapidly changing the strategies
      employed for the genetic diagnosis and research of rare diseases that involve a
      large number of genes. So far it is not clear whether these approaches perform
      significantly better than conventional single gene testing as requested by
      clinicians. The current yield of this traditional diagnostic approach depends on
      a complex of factors that include gene-specific phenotype traits, and the
      relative frequency of the involvement of specific genes. To gauge the impact of
      the paradigm shift that is occurring in molecular diagnostics, we assessed
      traditional Sanger-based sequencing (in 2011) and exome sequencing followed by
      targeted bioinformatics analysis (in 2012) for five different conditions that are
      highly heterogeneous, and for which our center provides molecular diagnosis. We
      find that exome sequencing has a much higher diagnostic yield than Sanger
      sequencing for deafness, blindness, mitochondrial disease, and movement
      disorders. For microsatellite-stable colorectal cancer, this was low under both
      strategies. Even if all genes that could have been ordered by physicians had been
      tested, the larger number of genes captured by the exome would still have led to
      a clearly superior diagnostic yield at a fraction of the cost. 

PMID- 24123793
TI  - Synthesis and characterization of cell-permeable caged phosphates that can be
      photolyzed by visible light or 800 nm two-photon photolysis.
AB  - We report the synthesis and photolytic properties of caged inorganic phosphates
      (Pi compounds) based on the 2-(4'-{bis[2-(2-methoxyethoxy)ethyl]amino}-4-nitro
      [1,1'-biphenyl]-3-yl)propan-1-ol (EANBP) and 7-(diethylamino)coumarin-4-yl]methyl
      (DEACM) protecting groups. The EANBP-Pi showed unprecedented photolysis
      efficiency at 405 nm, with 95 % release of free phosphate and a quantum yield of
      0.28. Thanks to the high two-photon sensitivity of the EANBP chromophore, Pi
      release through two-photon photolysis is also possible, with an action cross
      section of 20.5 GM at 800 nm. Two bioactivatable acetoxymethyl protection groups
      were added to the "caged-Pi" compounds. The resulting triesters of phosphoric
      acid were able to diffuse through the cellular membranes of plant cells. Once
      inside a cell, the cleavage of these biocleavable motifs by intracellular
      esterases allows intracellular accumulation of EANBP-Pi. Bis(AM)-EANBP-Pi
      therefore represents a very attractive tool for study of the Pi signal
      transduction cascade in living cells.

PMID- 24123794
TI  - Role of microRNA-27a in myoblast differentiation.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs that are critically
      involved in roles in various aspects of skeletal myogenesis. microRNA miR-27a
      promotes myoblast proliferation by targeting myostatin, a critical inhibitor of
      skeletal muscle development, but its mode of action in myoblast differentiation
      remains unclear. We have found that expression of miR-27a and myostatin were
      upregulated and downregulated, respectively, during myoblast differentiation.
      Overexpression of miR-27a increased the number of myosin heavy chain (MHC)
      positive cells and upregulated mRNA and protein of MyoD and myogenin. These
      findings indicate that miR-27a plays a role in enhancing myoblast
      differentiation. 

PMID- 24123795
TI  - Palladium-catalyzed cross-dehydrogenative functionalization of C(sp(2))-H Bonds.
AB  - The catalytic cross-dehydrogenative coupling (CDC) reaction has received intense
      attention in recent years. The attractive feature of this coupling process is the
      formation of a C-C bond from two C-H moieties under oxidative conditions. In this
      Focus Review, recent advances in the palladium-catalyzed CDC reactions of C(sp(2)
      )-H bond are summarized, with a focus on the period from 2011 to early 2013.

PMID- 24123796
TI  - Immunological behavior of in vitro digested egg-white lysozyme.
AB  - SCOPE: Besides its antimicrobial properties, lysozyme (LYS) is one of the major
      allergens from hen egg. This paper addresses the identification of the peptides
      produced upon in vitro gastrointestinal digestion of LYS, together with their IgE
      binding and biological activity as a contribution to the understanding of what
      makes it a relevant allergen. METHODS AND RESULTS: Simulated in vitro
      gastrointestinal digestion together with IgE binding, basophil degranulation, and
      peripheral blood mononuclear cells stimulation experiments were carried out.
      Identification of the fragments released was performed by HPLC-MS/MS and the
      immunoreactive products were analyzed by MALDI-TOF/TOF. Results showed that in
      vitro gastric and gastroduodenal digests of LYS maintained IgE binding, basophil
      activation capacity, and preserved T-cell immunogenicity. These biological
      activities could be attributed to either the persistence of intact LYS, due to
      incomplete gastric degradation and subsequent duodenal precipitation, the
      formation of fragment f(24-129) by chymotrypsin action on the soluble intact
      protein, or the release, upon combined gastric and pancreatic digestion, of
      immunoreactive peptides linked by disulphide bonds containing the epitopes f(57
      83) and f(108-122). CONCLUSION: The pH of gastric hydrolysis greatly determined
      the extent of subsequent duodenal digestion of LYS and the disclosure of relevant
      epitopes that could increase its allergenic potential.

PMID- 24123797
TI  - Diastereoselective synthesis of eight-membered-ring allenes from propargylic
      epoxides and aldehydes by silylene insertion into carbon-oxygen bonds.
AB  - Bent out of shape: Silver-catalyzed insertions of silylenes into propargylic C?O
      bonds of epoxides regioselectively form 1,2-silaoxetanes, which add to aldehydes
      to give the title allenes as single diastereomers (see scheme; Ts=4
      toluenesulfonyl). An X-ray crystal structure confirmed the stereochemistry of the
      allene, which is bent significantly from linearity (164 degrees ). 

PMID- 24123798
TI  - PTEN hamartoma tumor syndromes in childhood: description of two cases and a
      proposal for follow-up protocol.
AB  - PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth
      syndromes associated with germ-line mutations in the tumor suppressor PTEN gene
      located on 10q23.3. It is widely accepted that two of these disorders, Cowden
      syndrome and Bannayan-Riley-Ruvalcaba syndrome, are allelic conditions. Because
      PTEN mutations are not identifiable in every case of the PHTS phenotype, the
      inability to detect a mutation within the PTEN gene does not invalidate the
      clinical diagnosis of Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, in
      patients who meet diagnostic criteria for these disorders. PTEN mutations are
      associated with an increased risk for developing breast, thyroid, endometrial,
      and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS
      patient management. Although a consensus cancer surveillance protocol has not
      been formally instituted, all PTEN mutation carriers should adopt the cancer
      surveillance strategies proposed for patients with Cowden syndrome. In addition,
      because gastrointestinal and vascular complications can be more severe in
      Bannayan-Riley-Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan
      Riley-Ruvalcaba syndrome should be monitored from this point of view too. In this
      study, we report on two cases with Bannayan-Riley-Ruvalcaba phenotype that showed
      two different PTEN mutations. We also propose practice recommendations for
      management of PHTS patients.

PMID- 24123799
TI  - Successful treatment of an infant with CDA type II by intrauterine transfusions
      and postnatal stem cell transplantation.
AB  - Congenital dyserythropoietic anemias are rare hematological disorders leading to
      ineffective erythropoiesis with chronic anemia, complicated by iron overload.
      Here we present a remarkable clinical course of an infant with CDA type II who
      first presented as a severe fetal hydrops, requiring serial intrauterine red cell
      transfusions. While postnatal transfusion dependency persisted, the patient was
      successfully transplanted with a myeloablative conditioning regimen and
      peripheral blood stem cells of a matched donor. We believe that allogeneic HSCT
      is a reasonable therapeutic approach for patients with very severe CDA, even if
      only a matched unrelated donor is available.

PMID- 24123800
TI  - Dyeing and antibacterial activation with methylene blue of a cyclodextrin
      modified polyester vascular graft.
AB  - The aim of this study was to develop an antiseptic and blue dyed polyester (PET)
      vascular graft in order to reach two distinct properties: (i) the prevention of
      postoperative infections, (ii) the improvement of the graft compatibility with
      the coelioscopy surgical technique. This work consisted of dyeing a vascular
      prosthesis with methylene blue (MB) which is known as a cationic dye with
      antiseptic properties. Therefore, the functionalization of the PET fibers of the
      prosthesis with a cyclodextrin-citric acid polymer (PolyCD) was achieved in order
      to improve its sorption capacity. The NMR experiments demonstrated that a 1:2
      complex occurred between hydroxypropyl beta-cyclodextrin (HP-betaCD) and MB.
      Kinetic and sorption isotherm studies showed that an impregnation of the polyCD
      modified prosthesis (PET-CD) in a 1 g L(-1) of MB solution for 150 min was
      sufficient to reach the saturation of the device. Results proved that the
      adsorption mechanism followed the Langmuir model and a maximum of 20 mg g(-1) of
      MB on the graft. A sustained release of MB in batch tests was observed in PBS and
      in vitro microbiological assays displayed a prolongation of the bactericidal
      effect of PET-CD whose extent varied with the amount of MB preliminarily adsorbed
      onto the PET-CD.

PMID- 24123801
TI  - Total variance should drive data handling strategies in third generation
      proteomic studies.
AB  - Quantitative proteomics is entering its "third generation," where intricate
      experimental designs aim to increase the spatial and temporal resolution of
      protein changes. This paper re-analyses multiple internally consistent proteomic
      datasets generated from whole cell homogenates and fractionated brain tissue
      samples providing a unique opportunity to explore the different factors
      influencing experimental outcomes. The results clearly indicate that improvements
      in data handling are required to compensate for the increased mean CV associated
      with complex study design and intricate upstream tissue processing. Furthermore,
      applying arbitrary inclusion thresholds such as fold change in protein abundance
      between groups can lead to unnecessary exclusion of important and biologically
      relevant data. 

PMID- 24123802
TI  - Association of infant feeding and dietary intake on obesity prevalence in low
      income toddlers.
AB  - OBJECTIVE: This cross-sectional study assesses the independent and combined
      effects of breastfeeding (BF) and dietary intake, specifically sugar-sweetened
      beverages (SSB), on obesity prevalence in low-income, primarily Hispanic
      toddlers. METHODS: The following data were collected in 2011 via phone surveys
      with caregivers of 2295 low-income children (2-4 years) from Los Angeles County
      Women, Infants, and Children (WIC) programs: infant feeding, dietary intake,
      gestational diabetes status, birth weight, gestational age, and mother's BMI. WIC
      staff measured children's height and weight. Chi-square tests and binary logistic
      regressions assessed the independent and combined effects of BF and dietary
      intake on obesity prevalence. RESULTS: Compared to no BF, BF >= 12 mos was
      associated with a 47% reduction in obesity prevalence (AOR = 0.53, 95% CI 0.4
      0.8, P = 0.004). Compared to 2 + SSB/d, no SSB/d intake was associated with a 28%
      reduction in obesity prevalence (AOR = 0.72, 95% CI 0.5-1.0, P = 0.03). High
      intake of soda, diet soda, and fruit drinks were linked to increases in obesity
      prevalence. There was no effect of 100% juice, milk (plain or flavored) fruit,
      vegetable, fast food, or sweetened grain intake on obesity prevalence.
      CONCLUSIONS: These findings support encouragement of BF >= 12 mos and no SSB
      intake to prevent obesity in low-income, primarily Hispanic, toddlers.

PMID- 24123803
TI  - Mechanistic role of water on the rate and selectivity of Fischer-Tropsch
      synthesis on ruthenium catalysts.
AB  - Water increases Fischer-Tropsch synthesis (FTS) rates on Ru through H-shuttling
      processes. Chemisorbed hydrogen (H*) transfers its electron to the metal and
      protonates the O-atom of CO* to form COH*, which subsequently hydrogenates to
      *HCOH* in the kinetically relevant step. H2 O also increases the chain length of
      FTS products by mediating the H-transfer steps during reactions of alkyl groups
      with CO* to form longer-chain alkylidynes and OH*. 

PMID- 24123804
TI  - Low platelet counts after liver transplantation predict early posttransplant
      survival: the 60-5 criterion.
AB  - Platelets play a critical role in liver injury and regeneration. Thrombocytopenia
      is associated with increases in postoperative complications after partial
      hepatectomy, but it is unknown whether platelet counts could also predict
      outcomes after transplantation, a procedure that is often performed in
      thrombocytopenic patients. Therefore, the aim of this study was to evaluate
      whether platelet counts could be indicators of short- and long-term outcomes
      after liver transplantation (LT). Two hundred fifty-seven consecutive LT
      recipients (January 2003-December 2011) from our prospective database were
      analyzed. Preoperative and daily postoperative platelet counts were recorded
      until postoperative day 7 (POD7). Univariate and multivariate analyses were
      performed to assess whether low perioperative platelet counts were a risk factor
      for postoperative complications and graft and patient survival. The median
      pretransplant platelet count was 88 * 10(9) /L [interquartile range (IQR) = 58
      127 * 10(9) /L]. The lowest platelet counts occurred on POD3: the median was 56 *
      10(9) /L (IQR = 41-86 * 10(9) /L). Patients with low platelet counts on POD5 had
      higher rates of severe (grade IIIb/IV) complications [39% versus 29%, odds ratio
      (OR) = 1.09 (95% CI = 1.1-3.3), P = 0.02] and 90-day mortality [16% versus 8%, OR
      = 2.25 (95% CI = 1.0-5.0), P = 0.05]. In the multivariate analysis, POD5 platelet
      counts < 60 * 10(9) /L were identified as an independent risk factor for grade
      IIIb/IV complications [OR = 1.96 (95% CI = 1.07-3.56), P = 0.03)], graft survival
      [hazard ratio (HR) = 2.0 (95% CI = 1.1-3.6), P = 0.03)], and patient survival [HR
      = 2.2 (95% CI = 1.1-4.6), P = 0.03)]. The predictive value of platelet counts for
      graft and patient survival was lost in patients who survived 90 days. In
      conclusion, after LT, platelet counts < 60 * 10(9) /L on POD5 (the 60-5
      criterion) are an independent factor associated with severe complications and
      early graft and patient survival. These findings may help us to develop
      protective strategies or specific interventions for high-risk patients.

PMID- 24123805
TI  - Working through complexities of radial and brachial vasculature during
      transradial approach.
AB  - OBJECTIVES: The aim of this review is to discuss different methods of working
      through radial artery (RA) and brachial artery (BA) vascular complexities to
      increase the success rate of transradial approach (TRA). BACKGROUND: Anatomical
      complexities of RA and BA vasculature are an important reason for failure of TRA.
      There are few current data describing methods to overcome these challenges and
      reduce TRA failure. METHODS: A series of the primary RA and BA anatomical
      complexities are identified and management techniques to overcome these variants
      are discussed. RESULTS: RA and BA vascular complexities can be divided into three
      subsets including (1) radial artery spasm (RAS); (2) variant anatomy including
      tortuosity, loops, and anomalous origin of RA; (3) acquired abnormalities
      including perforations, atherosclerotic lesions, and calcification of RA. In
      depth discussion with supportive examples for the identification and management
      of these challenges are provided. A classification of RAS and perforations is
      shown and simple algorithms that have been developed for management of RAS,
      perforations and loops are explained. CONCLUSIONS: Despite lower rates of
      bleeding and vascular complications as compared to transfemoral approach (TFA),
      the adoption has been relatively slow particularly due to higher failure rates.
      Anatomical complexities of RA and BA vasculature play an important role for TRA
      failure cases. Using a simply framework to classify the anatomical or functional
      problem, and then approach these challenges in a logical sequence should
      facilitate management and increase success rate for TRA.

PMID- 24123806
TI  - Efficacy of plastic stent placement inside bile ducts for the treatment of
      unresectable malignant hilar obstruction (with videos).
AB  - BACKGROUND: Recent reports have addressed the utility of plastic stent (PS)
      placement inside bile ducts for treating biliary obstructions. Here, we evaluated
      the utility and safety of PS placement inside bile ducts for treating
      unresectable malignant hilar biliary obstruction. METHODS: We conducted a
      retrospective study of 27 patients with unresectable malignant hilar biliary
      obstruction who underwent intraductal modified PS placement. We modified the PS,
      by cutting off the distal end to facilitate insertion through the papilla of
      Vater, and attached a nylon thread to the distal end for removal. We evaluated
      complications, the time to recurrent biliary obstruction (TRBO), and
      removability. RESULTS: Bilateral stenting was performed in nine of the 27
      patients. Mild acute pancreatitis occurred in one patient (4%). Recurrent biliary
      obstruction (RBO) occurred in 16 patients (59%), with a median TRBO of 190 days
      (95% confidence interval: 174-205 days). Reintervention was necessary in 13 of
      the 16 patients (81%) with RBO, and we were able to remove the initial stents in
      all the patients who required reintervention. CONCLUSIONS: A relatively long
      stent patency period (>6 months) and removability make placement of a modified PS
      inside bile ducts a viable treatment for unresectable malignant hilar biliary
      obstruction.

PMID- 24123807
TI  - Enhanced osteoconductivity of titanium implant by polarization-induced surface
      charges.
AB  - This study introduces the application of method for electrically polarizing
      titanium implants coated with anatase TiO2 using microarc oxidation. It also
      describes the features of the electrically polarized titanium implants, on which
      surface charges are generated by the dipole moment of the TiO2 , and describes
      how the surface charges affect the implants' in vivo bone-implant integration
      capability. A comprehensive assessment using biomechanical, histomorphological,
      and radiographic analyses in a rabbit model was performed on polarized and
      nonpolarized implants. The electrically polarized surfaces accelerated the
      establishment of implant biomechanical fixation, compared with the nonpolarized
      surfaces. The percentage of the bone-implant contact ratio was higher using
      polarized implants than using nonpolarized implants. In contrast, the bone volume
      around the implants was not affected by polarization. Thus, using the polarized
      implant, this study identified that controlled surface charges have a significant
      effect on the properties of titanium implants. The application of the electrical
      polarization process and the polarization-enhanced osteoinductivity, which
      resulted in greater bone-implant integration, was clearly demonstrated.

PMID- 24123808
TI  - Cloning and sequencing of the chaetocin biosynthetic gene cluster.
AB  - How a fungus does it: The epidithiodiketopiperazine (ETP) fungal alkaloids, which
      include gliotoxin, have garnered much attention since their initial isolation.
      The cloning and sequencing of the biosynthetic gene cluster for another ETP,
      chaetocin A were used to suggest a route towards dimerization and sulfur
      incorporation in these molecules. 

PMID- 24123809
TI  - Registration of dynamic contrast-enhanced MRI of the common carotid artery using
      a fixed-frame template-based squared-difference method.
AB  - PURPOSE: This study examines template-based squared-difference registration for
      motion correction in dynamic contrast-enhanced (DCE) MRI studies of the carotid
      artery wall and compares the results of fixed-frame template-based registration
      with a previously proposed consecutive-frame registration method. MATERIALS AND
      METHODS: Ten T1-weighted black-blood, turbo spin-echo DCE-MRI studies of the
      carotid artery wall were used to test template-based squared-difference
      registration. An intermediate image from each series was selected as the fixed
      frame template for registration. Squared-difference minimization was used to
      align each image and template. Time-intensity curves generated from data aligned
      with template-based squared-difference registration were compared with gold
      standard curves created by drawing regions of interest on each image in the
      series. The results were also compared with unregistered data and data after
      consecutive-frame squared-difference registration. RESULTS: An analysis of
      variance test of root mean-square error values between gold standard curve and
      curves from unregistered data and data registered with consecutive-frame and
      fixed-frame template-based methods was significant (P < 0.005) with template
      based squared-difference registration producing curves that most closely matched
      the gold standard. CONCLUSION: A fixed-frame template-based squared-difference
      registration method was proposed and validated for alignment of DCE-MRI of
      carotid arteries.

PMID- 24123811
TI  - The older patient with diabetes: a practical approach.
AB  - Type 2 diabetes mellitus is very prevalent among persons aged 60-80 years old.
      This population is expected to increase in number and is characterized by the
      presence of comorbidities, long standing diabetes, frailty, high rate of
      cognitive impairment and limited life expectancy. These characteristics have a
      significant impact on diabetes and treatment among the elderly, much as diabetes
      predisposes to these conditions. In this article we will describe mechanisms that
      may lead to insulin resistance and diabetes among the elderly and also how these
      conditions contribute to the development of frailty and cognitive impairment.
      Hypoglycemia and it's consequences are important considerations when planning the
      treatment of diabetes. Treatment options in light of new goals and the danger of
      hypoglycemia will be detailed.

PMID- 24123810
TI  - A site-specific genetic modification for induction of pluripotency and subsequent
      isolation of derived lung alveolar epithelial type II cells.
AB  - Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in
      repairing defective lung alveoli. However, genetic abnormalities caused by vector
      integrations and low efficiency in generating hiPSCs, as well as difficulty in
      obtaining transplantable hiPSC-derived cell types are still major obstacles. Here
      we report a novel strategy using a single nonviral site-specific targeting vector
      with a combination of Tet-On inducible gene expression system, Cre/lox P
      switching gene expression system, and alveolar epithelial type II cell (ATIIC)
      specific Neomycin(R) transgene expression system. With this strategy, a single
      copy of all of the required transgenes can be specifically knocked into a site
      immediately downstream of beta-2-microglobulin (B2M) gene locus at a high
      frequency, without causing B2M dysfunction. Thus, the expression of reprogramming
      factors, Oct4, Sox2, cMyc, and Klf4, can be precisely regulated for efficient
      reprogramming of somatic cells into random integration-free or genetic mutation
      free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently
      removed after reprogramming by transient expression of Cre recombinase, and the
      resulting random integration-free and exogenous reprogramming factor-free hiPSCs
      can be selectively differentiated into a homogenous population of ATIICs. In
      addition, we show that these hiPSC-derived ATIICs exhibit ultrastructural
      characteristics and biological functions of normal ATIICs. When transplanted into
      bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re
      epithelialize injured alveoli to restore pulmonary function, preventing lung
      fibrosis and increasing survival without tumorigenic side effect. This strategy
      allows for the first time efficient generation of patient-specific ATIICs for
      possible future clinical applications.

PMID- 24123812
TI  - Significance of the hydrophobic residues 225-230 of apoA-I for the biogenesis of
      HDL.
AB  - We studied the significance of four hydrophobic residues within the 225-230
      region of apoA-I on its structure and functions and their contribution to the
      biogenesis of HDL. Adenovirus-mediated gene transfer of an apoA
      I[F225A/V227A/F229A/L230A] mutant in apoA-I-/- mice decreased plasma cholesterol,
      HDL cholesterol, and apoA-I levels. When expressed in apoA-I-/- * apoE-/- mice,
      approximately 40% of the mutant apoA-I as well as mouse apoA-IV and apoB-48
      appeared in the VLDL/IDL/LDL. In both mouse models, the apoA-I mutant generated
      small spherical particles of pre-beta- and alpha4-HDL mobility. Coexpression of
      the apoA-I mutant and LCAT increased and shifted the-HDL cholesterol peak toward
      lower densities, created normal alphaHDL subpopulations, and generated spherical
      HDL particles. Biophysical analyses suggested that the apoA-I[225-230] mutations
      led to a more compact folding that may limit the conformational flexibility of
      the protein. The mutations also reduced the ability of apoA-I to promote ABCA1
      mediated cholesterol efflux and to activate LCAT to 31% and 66%, respectively, of
      the WT control. Overall, the apoA-I[225-230] mutations inhibited the biogenesis
      of-HDL and led to the accumulation of immature pre-beta- and alpha4-HDL
      particles, a phenotype that could be corrected by administration of LCAT.

PMID- 24123813
TI  - Screening for major and minor depression in a multiethnic sample of Asian primary
      care patients: a comparison of the nine-item Patient Health Questionnaire (PHQ-9)
      and the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS
      SR16 ).
AB  - INTRODUCTION: Depression is common, disabling, and the single most important
      factor leading to suicide, yet it is underdiagnosed in busy primary care
      settings. A key challenge facing primary care clinicians in Asia is the selection
      of instruments to facilitate depression screening. Although the nine-item Patient
      Health Questionnaire (PHQ-9) and 16-item Quick Inventory of Depressive
      Symptomatology - Self-Report (QIDS-SR16 ) are used internationally, they have not
      been directly compared or widely validated in Asian primary care populations.
      This study aimed to validate the PHQ-9 and QIDS-SR16 against a structured
      interview diagnosis of Diagnostic and Statistical Manual, 4th Edition, depression
      based on the Mini-International Neuropsychiatric Interview in a multiethnic Asian
      sample. METHODS: From April through August 2011, we enrolled 400 English-speaking
      Singaporean primary care patients. Participants completed a demographic data
      form, the PHQ-9, and the QIDS-SR16 . They were assessed independently for major
      and minor depression using the Mini-International Neuropsychiatric Interview.
      RESULTS: Sensitivity and specificity for diagnosing major depression were 91.7%
      and 72.2%, respectively, for the PHQ-9 (optimal cutoff score of 6), and 83.3% and
      84.7%, respectively, for the QIDS-SR16 (optimal cutoff score of 9). The QIDS-SR16
      also detected minor depression at an optimal cutoff score of 7, with a
      sensitivity of 94.4% and specificity of 77.9%. The PHQ-9 and QIDS-SR16 showed
      good internal consistency (Cronbach's alpha: 0.87 and 0.79, respectively) and
      good convergent validity (correlation coefficient: r = 0.73, P < 0.001). The
      overall prevalence of major and minor depressive disorders was 9%. DISCUSSION:
      The PHQ-9 and QIDS-SR16 appear to be valid and reliable for depression screening
      in Asian primary care settings.

PMID- 24123814
TI  - Structure and function of a novel LD-carboxypeptidase a involved in peptidoglycan
      recycling.
AB  - Approximately 50% of cell wall peptidoglycan in Gram-negative bacteria is
      recycled with each generation. The primary substrates used for peptidoglycan
      biosynthesis and recycling in the cytoplasm are GlcNAc-MurNAc(anhydro)
      tetrapeptide and its degradation product, the free tetrapeptide. This complex
      process involves ~15 proteins, among which the cytoplasmic enzyme ld
      carboxypeptidase A (LdcA) catabolizes the bond between the last two l- and d
      amino acid residues in the tetrapeptide to form the tripeptide, which is then
      utilized as a substrate by murein peptide ligase (Mpl). LdcA has been proposed as
      an antibacterial target. The crystal structure of Novosphingobium aromaticivorans
      DSM 12444 LdcA (NaLdcA) was determined at 1.89-A resolution. The enzyme was
      biochemically characterized and its interactions with the substrate modeled,
      identifying residues potentially involved in substrate binding. Unaccounted
      electron density at the dimer interface in the crystal suggested a potential site
      for disrupting protein-protein interactions should a dimer be required to perform
      its function in bacteria. Our analysis extends the identification of functional
      residues to several other homologs, which include enzymes from bacteria that are
      involved in hydrocarbon degradation and destruction of coral reefs. The NaLdcA
      crystal structure provides an alternate system for investigating the structure
      function relationships of LdcA and increases the structural coverage of the
      protagonists in bacterial cell wall recycling. 

PMID- 24123815
TI  - Identification of a DNA-damage-inducible regulon in Acinetobacter baumannii.
AB  - The transcriptional response of Acinetobacter baumannii, a major cause of
      nosocomial infections, to the DNA-damaging agent mitomycin C (MMC) was studied
      using DNA microarray technology. Most of the 39 genes induced by MMC were related
      to either prophages or encoded proteins involved in DNA repair. Electrophoretic
      mobility shift assays demonstrated that the product of the A. baumannii MMC
      inducible umuD gene (umuDAb) specifically binds to the palindromic sequence
      TTGAAAATGTAACTTTTTCAA present in its promoter region. Mutations in this
      palindromic region abolished UmuDAb protein binding. A comparison of the promoter
      regions of all MMC-induced genes identified four additional transcriptional units
      with similar palindromic sequences recognized and specifically bound by UmuDAb.
      Therefore, the UmuDAb regulon consists of at least eight genes encoding seven
      predicted error-prone DNA polymerase V components and DddR, a protein of unknown
      function. Expression of these genes was not induced in the MMC-treated recA
      mutant. Furthermore, inactivation of the umuDAb gene resulted in the deregulation
      of all DNA-damage-induced genes containing the described palindromic DNA motif.
      Together, these findings suggest that UmuDAb is a direct regulator of the DNA
      damage response in A. baumannii. 

PMID- 24123816
TI  - SmbFT, a putative ABC transporter complex, confers protection against the
      lantibiotic Smb in Streptococci.
AB  - Streptococcus mutans, a dental pathogen, secretes different kinds of lantibiotic
      and nonlantibiotic bacteriocins. For self-protection, a bacteriocin producer
      strain must possess one or more cognate immunity mechanisms. We report here the
      identification of one such immunity complex in S. mutans strain GS-5 that confers
      protection against Smb, a two-component lantibiotic. The immunity complex that we
      identified is an ABC transporter composed of two proteins: SmbF (the ATPase
      component) and SmbT (the permease component). Both of the protein-encoding genes
      are located within the smb locus. We show that GS-5 becomes sensitized to Smb
      upon deletion of smbT, which makes the ABC transporter nonfunctional. To
      establish the role SmbFT in providing immunity, we heterologously expressed this
      ABC transporter complex in four different sensitive streptococcal species and
      demonstrated that it can confer resistance against Smb. To explore the
      specificity of SmbFT in conferring resistance, we tested mutacin IV (a
      nonlantibiotic), nisin (a single peptide lantibiotics), and three peptide
      antibiotics (bacitracin, polymyxin B, and vancomycin). We found that SmbFT does
      not recognize these structurally different peptides. We then tested whether SmbFT
      can confer protection against haloduracin, another two-component lantibiotic that
      is structurally similar to Smb; SmbFT indeed conferred protection against
      haloduracin. SmbFT can also confer protection against an uncharacterized but
      structurally similar lantibiotic produced by Streptococcus gallolyticus. Our data
      suggest that SmbFT truly displays immunity function and confer protection against
      Smb and structurally similar lantibiotics. 

PMID- 24123817
TI  - Structural and functional characterization of an orphan ATP-binding cassette
      ATPase involved in manganese utilization and tolerance in Leptospira spp.
AB  - Pathogenic Leptospira species are the etiological agents of the widespread
      zoonotic disease leptospirosis. Most organisms, including Leptospira, require
      divalent cations for proper growth, but because of their high reactivity, these
      metals are toxic at high concentrations. Therefore, bacteria have acquired
      strategies to maintain metal homeostasis, such as metal import and efflux. By
      screening Leptospira biflexa transposon mutants for their ability to use Mn(2+),
      we have identified a gene encoding a putative orphan ATP-binding cassette (ABC)
      ATPase of unknown function. Inactivation of this gene in both L. biflexa and L.
      interrogans strains led to mutants unable to grow in medium in which iron was
      replaced by Mn(2+), suggesting an involvement of this ABC ATPase in divalent
      cation uptake. A mutation in this ATPase-coding gene increased susceptibility to
      Mn(2+) toxicity. Recombinant ABC ATPase of the pathogen L. interrogans exhibited
      Mg(2+)-dependent ATPase activity involving a P-loop motif. The structure of this
      ATPase was solved from a crystal containing two monomers in the asymmetric unit.
      Each monomer adopted a canonical two-subdomain organization of the ABC ATPase
      fold with an alpha/beta subdomain containing the Walker motifs and an alpha
      subdomain containing the ABC signature motif (LSSGE). The two monomers were
      arranged in a head-to-tail orientation, forming a V-shaped particle with all the
      conserved ABC motifs at the dimer interface, similar to functional ABC ATPases.
      These results provide the first structural and functional characterization of a
      leptospiral ABC ATPase. 

PMID- 24123818
TI  - A mutation in the N domain of Escherichia coli lon stabilizes dodecamers and
      selectively alters degradation of model substrates.
AB  - Escherichia coli Lon, an ATP-dependent AAA(+) protease, recognizes and degrades
      many different substrates, including the RcsA and SulA regulatory proteins. More
      than a decade ago, the E240K mutation in the N domain of Lon was shown to prevent
      degradation of RcsA but not SulA in vivo. Here, we characterize the biochemical
      properties of the E240K mutant in vitro and present evidence that the effects of
      this mutation are complex. For example, Lon(E240K) exists almost exclusively as a
      dodecamer, whereas wild-type Lon equilibrates between hexamers and dodecamers.
      Moreover, Lon(E240K) displays degradation defects in vitro that do not correlate
      in any simple fashion with degron identity, substrate stability, or dodecamer
      formation. The Lon sequence segment near residue 240 is known to undergo
      nucleotide-dependent conformational changes, and our results suggest that this
      region may be important for coupling substrate binding with allosteric activation
      of Lon protease and ATPase activity. 

PMID- 24123819
TI  - Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine
      production and immunomodulation by Lactobacillus reuteri.
AB  - Human microbiome-derived strains of Lactobacillus reuteri potently suppress
      proinflammatory cytokines like human tumor necrosis factor (TNF) by converting
      the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses
      mitogen-activated protein (MAP) kinase activation and cytokine production by
      signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of
      the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475
      highlighted numerous genes that were highly expressed during the stationary phase
      of growth, when TNF suppression is most potent. One such gene was found to be a
      regulator of genes involved in histidine-histamine metabolism by this probiotic
      species. During the course of these studies, this gene was renamed the
      Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is
      essential for human TNF suppression by L. reuteri and expression of the histidine
      decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of
      rsiR resulted in diminished TNF suppression in vitro and reduced anti
      inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced
      mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was
      unable to suppress colitis and resulted in greater concentrations of serum
      amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter
      region targeted by rsiR was defined by reporter gene experiments. These studies
      support the presence of a regulatory gene, rsiR, which modulates the expression
      of a gene cluster known to mediate immunoregulation by probiotics at the
      transcriptional level. These findings may point the way toward new strategies for
      controlling gene expression in probiotics by dietary interventions or microbiome
      manipulation. 

PMID- 24123820
TI  - Structural and population characterization of MrkD, the adhesive subunit of type
      3 fimbriae.
AB  - Type 3 fimbriae are adhesive organelles found in enterobacterial pathogens. The
      fimbriae promote biofilm formation on biotic and abiotic surfaces; however, the
      exact identity of the receptor for the type 3 fimbriae adhesin, MrkD, remains
      elusive. We analyzed naturally occurring structural and functional variabilities
      of the MrkD adhesin from Klebsiella pneumoniae and Escherichia coli isolates of
      diverse origins. We identified a total of 33 allelic variants of mrkD among 90 K.
      pneumoniae isolates and 10 allelic variants among 608 E. coli isolates, encoding
      11 and 9 protein variants, respectively. Based on the level of accumulated silent
      variability between the alleles, mrkD was acquired a relatively long time ago in
      K. pneumoniae but recently in E. coli. However, unlike K. pneumoniae, mrkD in E.
      coli is actively evolving under a strong positive selection by accumulation of
      mutations, often targeting the same positions in the protein. Several naturally
      occurring MrkD protein variants from E. coli were found to be significantly less
      adherent when tested in a mannan-binding assay and showed reduced biofilm-forming
      capacity. Functional examination of the MrkD adhesin in flow chamber experiments
      determined that it interacts with Saccharomyces cerevisiae cells in a shear
      dependent manner, i.e., the binding is catch-bond-like and enhanced under
      increasing shear conditions. Homology modeling strongly suggested that MrkD has a
      two-domain structure, comprising a pilin domain anchoring the adhesin to the
      fimbrial shaft and a lectin domain containing the binding pocket; this is similar
      to structures found in other catch-bond-forming fimbrial adhesins in
      enterobacteria. 

PMID- 24123821
TI  - Essential roles for Mycobacterium tuberculosis Rel beyond the production of
      (p)ppGpp.
AB  - In Mycobacterium tuberculosis, the stringent response to amino acid starvation is
      mediated by the M. tuberculosis Rel (RelMtb) enzyme, which transfers a
      pyrophosphate from ATP to GDP or GTP to synthesize ppGpp and pppGpp,
      respectively. (p)ppGpp then influences numerous metabolic processes. RelMtb also
      encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into
      pyrophosphate and GDP or GTP. RelMtb is required for chronic M. tuberculosis
      infection in mice; however, it is unknown which catalytic activity of RelMtb
      mediates pathogenesis and whether (p)ppGpp itself is necessary. In order to
      individually investigate the roles of (p)ppGpp synthesis and hydrolysis during M.
      tuberculosis pathogenesis, we generated RelMtb point mutants that were either
      synthetase dead (RelMtb(H344Y)) or hydrolase dead (RelMtb(H80A)). M. tuberculosis
      strains expressing the synthetase-dead RelMtb(H344Y) mutant did not persist in
      mice, demonstrating that the RelMtb (p)ppGpp synthetase activity is required for
      maintaining bacterial titers during chronic infection. Deletion of a second
      predicted (p)ppGpp synthetase had no effect on pathogenesis, demonstrating that
      RelMtb was the major contributor to (p)ppGpp production during infection.
      Interestingly, expression of an allele encoding the hydrolase-dead RelMtb mutant,
      RelMtb(H80A), that is incapable of hydrolyzing (p)ppGpp but still able to
      synthesize (p)ppGpp decreased the growth rate of M. tuberculosis and changed the
      colony morphology of the bacteria. In addition, RelMtb(H80A) expression during
      acute or chronic M. tuberculosis infection in mice was lethal to the infecting
      bacteria. These findings highlight a distinct role for RelMtb-mediated (p)ppGpp
      hydrolysis that is essential for M. tuberculosis pathogenesis. 

PMID- 24123822
TI  - Phosphorylated DegU manipulates cell fate differentiation in the Bacillus
      subtilis biofilm.
AB  - Cell differentiation is ubiquitous and facilitates division of labor and
      development. Bacteria are capable of multicellular behaviors that benefit the
      bacterial community as a whole. A striking example of bacterial differentiation
      occurs throughout the formation of a biofilm. During Bacillus subtilis biofilm
      formation, a subpopulation of cells differentiates into a specialized population
      that synthesizes the exopolysaccharide and the TasA amyloid components of the
      extracellular matrix. The differentiation process is indirectly controlled by the
      transcription factor Spo0A that facilitates transcription of the eps and tapA
      (tasA) operons. DegU is a transcription factor involved in regulating biofilm
      formation. Here, using a combination of genetics and live single-cell cytological
      techniques, we define the mechanism of biofilm inhibition at high levels of
      phosphorylated DegU (DegU~P) by showing that transcription from the eps and tapA
      promoter regions is inhibited. Data demonstrating that this is not a direct
      regulatory event are presented. We demonstrate that DegU~P controls the frequency
      with which cells activate transcription from the operons needed for matrix
      biosynthesis in favor of an off state. Subsequent experimental analysis led us to
      conclude that DegU~P functions to increase the level of Spo0A~P, driving cell
      fate differentiation toward the terminal developmental process of sporulation. 

PMID- 24123823
TI  - Disconnecting in vitro ESX-1 secretion from mycobacterial virulence.

PMID- 24123824
TI  - A Zn-dependent metallopeptidase is responsible for sensitivity to LsbB, a class
      II leaderless bacteriocin of Lactococcus lactis subsp. lactis BGMN1-5.
AB  - Lactococcus lactis subsp. lactis BGMN1-5 produces a leaderless class II
      bacteriocin called LsbB. To identify the receptor for LsbB, a cosmid library of
      the LsbB-sensitive strain BGMN1-596 was constructed. About 150 cosmid clones were
      individually isolated and transferred to LsbB-resistant mutants of BGMN1-596.
      Cosmid pAZILcos/MN2, carrying a 40-kb insert, was found to restore LsbB
      sensitivity in LsbB-resistant mutants. Further subcloning revealed that a 1.9-kb
      fragment, containing only one open reading frame, was sufficient to restore
      sensitivity. The fragment contains the gene yvjB coding for a Zn-dependent
      membrane-bound metallopeptidase, suggesting that this gene may serve as the
      receptor for LsbB. Further support for this notion derives from several
      independent experiments: (i) whole-genome sequencing confirmed that all LsbB
      resistant mutants contain mutations in yvjB; (ii) disruption of yvjB by direct
      gene knockout rendered sensitive strains BGMN1-596 and IL1403 resistant to LsbB;
      and (iii) most compellingly, heterologous expression of yvjB in naturally
      resistant strains of other species, such as Lactobacillus paracasei and
      Enterococcus faecalis, also rendered them sensitive to the bacteriocin. To our
      knowledge, this is the first time a membrane-bound peptidase gene has been shown
      to be involved in bacteriocin sensitivity in target cells. We also demonstrated a
      novel successful approach for identifying bacteriocin receptors. 

PMID- 24123825
TI  - The ETFDH c.158A>G variation disrupts the balanced interplay of ESE- and ESS
      binding proteins thereby causing missplicing and multiple Acyl-CoA
      dehydrogenation deficiency.
AB  - Multiple acyl-CoA dehydrogenation deficiency is a disorder of fatty acid and
      amino acid oxidation caused by defects of electron transfer flavoprotein (ETF) or
      its dehydrogenase (ETFDH). A clear relationship between genotype and phenotype
      makes genotyping of patients important not only diagnostically but also for
      prognosis and for assessment of treatment. In the present study, we show that a
      predicted benign ETFDH missense variation (c.158A>G/p.Lys53Arg) in exon 2 causes
      exon skipping and degradation of ETFDH protein in patient samples. Using splicing
      reporter minigenes and RNA pull-down of nuclear proteins, we show that the
      c.158A>G variation increases the strength of a preexisting exonic splicing
      silencer (ESS) motif UAGGGA. This ESS motif binds splice inhibitory hnRNP A1,
      hnRNP A2/B1, and hnRNP H proteins. Binding of these inhibitory proteins prevents
      binding of the positive splicing regulatory SRSF1 and SRSF5 proteins to nearby
      and overlapping exonic splicing enhancer elements and this causes exon skipping.
      We further suggest that binding of hnRNP proteins to UAGGGA is increased by
      triggering synergistic hnRNP H binding to GGG triplets located upstream and
      downsteam of the UAGGGA motif. A number of disease-causing exonic elements that
      induce exon skipping in other genes have a similar architecture as the one in
      ETFDH exon 2. 

PMID- 24123826
TI  - Maximizing the accuracy of field-derived numeric nutrient criteria in water
      quality regulations.
AB  - High levels of the nutrients nitrogen and phosphorus can cause unhealthy
      biological or ecological conditions in surface waters and prevent the attainment
      of their designated uses. Regulatory agencies are developing numeric criteria for
      these nutrients in an effort to ensure that the surface waters in their
      jurisdictions remain healthy and productive, and that water quality standards are
      met. These criteria are often derived using field measurements that relate
      nutrient concentrations and other water quality conditions to expected biological
      responses such as undesirable growth or changes in aquatic plant and animal
      communities. Ideally, these numeric criteria can be used to accurately "diagnose"
      ecosystem health and guide management decisions. However, the degree to which
      numeric nutrient criteria are useful for decision making depends on how
      accurately they reflect the status or risk of nutrient-related biological
      impairments. Numeric criteria that have little predictive value are not likely to
      be useful for managing nutrient concerns. This paper presents information on the
      role of numeric nutrient criteria as biological health indicators, and the
      potential benefits of sufficiently accurate criteria for nutrient management. In
      addition, it describes approaches being proposed or adopted in states such as
      Florida and Maine to improve the accuracy of numeric criteria and criteria-based
      decisions. This includes a preference for developing site-specific criteria in
      cases where sufficient data are available, and the use of nutrient concentration
      and biological response criteria together in a framework to support designated
      use attainment decisions. Together with systematic planning during criteria
      development, the accuracy of field-derived numeric nutrient criteria can be
      assessed and maximized as a part of an overall effort to manage nutrient water
      quality concerns.

PMID- 24123827
TI  - Photoactivation of a psoralen-blocked luciferase gene by blue light.
AB  - A single psoralen cross-link completely blocks expression of a gene. An
      aminopyrene derivative has been found that allows the efficient light-triggered
      activation of cross-linked genes by UV or blue light. This paves the way to apply
      such psoralen cross-links for the photocleavable protection of nucleic acids. 

PMID- 24123828
TI  - Multiple reduction of 2,5-bis(borolyl)thiophene: isolation of a negative
      bipolaron by comproportionation.
AB  - The 2,5-bis(borolyl)thiophene 2, a conjugated acceptor-pi-acceptor system, can be
      reduced to the monoradical anion [2](.-) , the dianion [2](2-) , and the
      tetraanion [2](4-) . The dianion [2](2-) was also prepared by a
      comproportionation reaction and features an absorption maximum in the near-IR
      region (lambdamax =800 nm), which is characteristic of a bipolaron with a
      quinoidal structure. 

PMID- 24123829
TI  - 1,3,5-Trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone directly targets heat
      shock protein 27 in hepatocellular carcinoma.
AB  - We previously showed that the small molecule 1,3,5-trihydroxy-13,13-dimethyl-2H
      pyran [7,6-b] xanthone (TDP) induces apoptosis in hepatocellular carcinoma (HCC)
      by suppressing Hsp27 expression, although the mechanism is not fully understood.
      To investigate the functional association between TDP and Hsp27 protein in HCC,
      recombinant Hsp27 protein was incubated with TDP at room temperature, and assayed
      by mass spectrum (MS) and natural electrophoresis. TDP effectively stimulated
      Hsp27 to form aggregates ex vitro, leading to suppression of its chaperone
      activity. The aggregates were degraded by the ubiquitin-proteasome (UPS) pathway.
      TDP directly interacted with Asp17 and Phe55 in chain C of Hsp27 on the basis of
      bioinformatic prediction. In conclusion, Hsp27 is a direct target of TDP in its
      anti-cancer activity, which provides strong support for a clinical application. 

PMID- 24123830
TI  - Effects of corticosterone and DHEA on doublecortin immunoreactivity in the song
      control system and hippocampus of adult song sparrows.
AB  - Adult neuroplasticity is strongly influenced by steroids. In particular,
      corticosterone (CORT) and dehydroepiandrosterone (DHEA) can have opposing
      effects, where CORT reduces while DHEA increases neurogenesis and neuron
      recruitment. It has been previously shown that in adult male song sparrows, DHEA
      treatment increases neuron recruitment throughout the telencephalon, including
      the lateral ventricular zone, while the effect of CORT treatment is restricted to
      HVC, one of the song control regions. These data suggest that the two steroids
      may differentially affect proliferation, migration, differentiation, and/or
      survival of new neurons. To determine if CORT or DHEA alters the migration and
      differentiation of young neurons, we examined an endogenous marker of migrating
      immature neurons, doublecortin (DCX), in HVC and hippocampus of adult male song
      sparrows that were treated with CORT and/or DHEA for 28 days. In HVC, DHEA
      increased the number of DCX-labeled round cells, while CORT had no main effect on
      the number of DCX-labeled cells. Furthermore, DHEA increased the area covered by
      DCX immunoreactivity in HVC, regardless of CORT treatment. In the hippocampus,
      neither DHEA nor CORT affected DCX immunoreactivity. These results suggest that
      DHEA enhances migration and differentiation of young neurons into HVC while CORT
      does not affect the process, whether in the presence of DHEA or not. 

PMID- 24123831
TI  - Sample preparation for two-dimensional gel electrophoresis: considering the
      composition of biological material.
AB  - Comparative proteomic analyses in ecotoxicology and related fields require
      reproducible display of as many proteins as possible. In addition, it should be
      possible to carry out a quantitative comparison in a reliable manner. Sample
      preparation represents one of the essential steps toward these aims. In their
      work, Wu et al. describe how to deal with different recalcitrant tissues of
      varying species (Proteomics 2013, 13, 3205-3210). Their work underlines the
      necessity to adapt sample preparation to the specific requirements of the
      biological material. Beyond that Wu et al. present TRIzol(r) as feasible means
      for combined extraction of proteins and RNA. Indeed, using TRI-reagent extraction
      for proteomics, they resolve two problems at a time: that of removing
      contaminating compounds and that of simultaneous analysis of gene and protein
      expression. 

PMID- 24123832
TI  - Prediction of the wine polyphenol metabolic space: an application of the Phenol
      Explorer database.
AB  - SCOPE: Knowledge of in vivo polyphenol metabolites derived from the consumption
      of red wine could be key to understanding its health benefits. This work aimed to
      predict the wine polyphenol metabolic space in biofluids by using all available
      data compiled in the Phenol-Explorer database. METHODS AND RESULTS: A search
      strategy was developed for Phenol-Explorer to obtain the widest range of
      metabolites related to wine consumption. A total of 97 metabolites have been
      described in intervention studies with wine and related products (n = 37), and
      after consumption of pure compounds known to be wine constituents (n = 90). These
      97 metabolites, derived from host and microbial metabolism of several classes of
      polyphenols, were found in plasma and urine samples and some of them have
      demonstrated higher or lower biological activities than the parent compound in in
      vitro studies. The metabolites have been linked to generate, for the first time,
      a global pathway map of wine in vivo polyphenol metabolism. CONCLUSION: The
      retrieval of the widest range of metabolites so far described and their assembly
      as a metabolic pathway map could aid the identification of possible biomarkers of
      wine consumption and improve current understanding of the health effects of wine
      consumption.

PMID- 24123833
TI  - Developmental disease and cancer: biological and clinical overlaps.
AB  - Numerous parallelisms exist between development and cancer. In this article, I
      review some of the founding ideas linking development and cancer, and highlight
      clinical conditions exhibiting features of both developmental derangement and
      cancer predisposition, including cohesinopathies, rasopathies, phakomatoses,
      Proteus syndrome and other overgrowth disorders, recessive chromosome breakage
      syndromes, and dominant hereditary cancer syndromes. I suggest that these
      disorders encompass a continuous spectrum spanning clinical genetics and clinical
      oncology, and derive some general implications that might be useful in the future
      for the treatment of these diseases.

PMID- 24123834
TI  - CCDC3 is specifically upregulated in omental adipose tissue in subjects with
      abdominal obesity.
AB  - OBJECTIVE: The aim of this study was to search for novel markers of visceral
      adiposity. METHODS: Visceral (omental) and subcutaneous adipose tissues were
      obtained from 43 Japanese men. Microarray analysis using total RNA from visceral
      and subcutaneous adipose tissues obtained from five men with abdominal obesity
      and five nonobese men was first conducted. Then the expression pattern of
      candidate genes identified in the human study in mouse models of adiposity was
      examined. RESULTS: Among 30,500 genes evaluated, the mRNA expression of CCDC3
      (encoding coiled-coil domain-containing protein 3) was upregulated in omental
      adipose tissues from abdominally obese subjects (3.07-fold) but not in
      subcutaneous adipose tissues (0.89-fold). Similar expression patterns were found
      in two distinct mouse models of obesity. In the analysis of all 43 men, CCDC3
      mRNA levels in omental, but not in subcutaneous adipose tissue, were positively
      correlated with waist circumference and body mass index. CCDC3 was predicted to
      be a secretory protein, which was confirmed by western blotting, as overexpressed
      CCDC3 was secreted into the culture media. CONCLUSIONS: The expression of CCDC3
      is specifically increased in visceral adipose tissues in abdominally obese
      subjects. These results suggest that CCDC3 is a potential biomarker for
      estimating visceral adiposity.

PMID- 24123835
TI  - Early-onset and late-onset heart failure after liver transplantation.

PMID- 24123836
TI  - Endothelin-1 gene polymorphisms and risk of chemoresistant pediatric
      osteosarcoma.
AB  - BACKGROUND: Osteosarcoma (OS) is the most common childhood bone cancer.
      Chemoresistance is the principal reason for poor survival and disease recurrence
      in OS patients, and ET-1 reportedly plays an important role in the development of
      chemoresistance in OS cells. In the present study, we for the first time explored
      the association of endothelin-1 (ET-1) SNPs and haplotypes with the risk of
      chemoresistant pediatric OS. PROCEDURE: We genotyped three SNPs (rs1800541,
      rs2070699, and rs5370) in the ET-1 gene in a case-control study, using 350 pairs
      of age, sex, and tumor location and stage matched pediatric patients with OS.
      Patients who showed <90% tumor necrosis after neochemotherapy were defined as
      poor responders (cases), and those who showed >=90% tumor necrosis were defined
      as good responders (controls). RESULTS: The G allele at rs1800541 and the G
      allele at rs2070699 were associated with reduced and increased risk of
      chemoresistant OS, respectively. The rs1800541-rs2070699 haplotypes TG and GT
      were respectively associated with increased (P = 0.012; adjusted OR, 1.82; 95%
      CI, 1.10-5.65) and reduced (P = 0.009; adjusted OR, 0.25; 95% CI, 0.14-0.84) risk
      of chemoresistant OS. The TG and the GT haplotypes have a gene-dosage effect on
      increasing and decreasing the ET-1 expression in primary OS tumor cells from
      chemoresistant pediatric OS subjects, respectively. CONCLUSIONS: This study
      provides the first evidence of an association between the ET-1 gene SNPs and
      haplotypes and the risk of chemoresistant pediatric OS, potentially adding new
      insights into the pathophysiology and treatment of chemoresistant OS.

PMID- 24123837
TI  - Bonding between oxide ceramics and adhesive cement systems: a systematic review.
AB  - The following aims were set for this systematic literature review: (a) to make an
      inventory of existing methods to achieve bondable surfaces on oxide ceramics and
      (b) to evaluate which methods might provide sufficient bond strength. Current
      literature of in vitro studies regarding bond strength achieved using different
      surface treatments on oxide ceramics in combination with adhesive cement systems
      was selected from PubMed and systematically analyzed and completed with reference
      tracking. The total number of publications included for aim a was 127 studies, 23
      of which were used for aim b. The surface treatments are divided into seven main
      groups: as-produced, grinding/polishing, airborne particle abrasion, surface
      coating, laser treatment, acid treatment, and primer treatment. There are large
      variations, making comparison of the studies difficult. An as-produced surface of
      oxide ceramic needs to be surface treated to achieve durable bond strength.
      Abrasive surface treatment and/or silica-coating treatment with the use of primer
      treatment can provide sufficient bond strength for bonding oxide ceramics. This
      conclusion, however, needs to be confirmed by clinical studies. There is no
      universal surface treatment. Consideration should be given to the specific
      materials to be cemented and to the adhesive cement system to be used.

PMID- 24123838
TI  - New approach for the clinical monitoring of 25-hydroxyvitamin D3 and 25
      hydroxyvitamin D2 by ultra high performance liquid chromatography with MS/MS
      based on the standard reference material 972.
AB  - Biomarkers, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 , are important
      indicators of the vitamin D general status and are monitored in several
      pathophysiological disorders, such as osteoporosis, diabetes, heart disease, etc.
      A novel ultra-HPLC with MS/MS methodology for the analysis of 25-hydroxyvitamin D
      derivatives coupled with a very simple and highly rapid sample preparation step
      was developed. Analytical parameters obtained showed linearity (R(2) ) above
      0.999 for both vitamins with accuracies between 95.8 and 102%. The LODs were as
      low as 0.22 and 0.67 nmol/L for 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 ,
      respectively. Intra-assay precision (%RSD) was lower than 4.5%, and inter-assay
      precision (%RSD) was lower than 6.5%. The feasibility of the developed
      methodology to be applied in clinical routine analysis has been proved by its
      application in blood samples from non-agenarian patients, patients with familial
      hypercholesterolemia and patients suffering from age-related macular
      degeneration. 

PMID- 24123839
TI  - The interaction between cepharanthine and two serum albumins: multiple
      spectroscopic and chemometric investigations.
AB  - The binding modes of cepharanthine (CEPT) with bovine serum albumin (BSA) and
      human serum albumin (HSA) have been established by reproducing physiological
      conditions, which is very important to understand the pharmacokinetics and
      toxicity of CEPT. These spectral data were further analyzed by the multivariate
      curve resolution-alternating least squares method. Moreover, the concentration
      profiles and pure spectra of three species (BSA/HSA, CEPT and CEPT-BSA/HSA) and
      the apparent equilibrium constants K(app) were evaluated. The experimental
      results showed that CEPT could quench the fluorescence intensity of BSA/HSA by a
      combined quenching (static and dynamic) procedure. The binding constant (K), the
      thermodynamic parameters (DeltaG, DeltaH and DeltaS) and binding subdomain were
      measured, and indicated that CEPT could spontaneously bind to BSA/HSA on
      subdomain IIA through the hydrophobic interactions. The effect of CEPT on the
      secondary structure of proteins has been analyzed by circular dichroism, 3D
      fluorescence and Fourier transform infrared spectra. The binding distance between
      CEPT and tryptophan of BSA/HSA was 2.305/1.749 nm, which is based on the Forster
      resonance energy transfer theory.

PMID- 24123840
TI  - Reticulated bioactive scaffolds with improved textural properties for bone tissue
      engineering: nanostructured surfaces and porosity.
AB  - Organised nanoporous SBA-15 type silica precursor (SP) particulate material has
      been processed into three-dimensional macroporous, reticulated structures using a
      novel strategy consisting of blending increasing percentages of SP with a SiO2 
      CaO-P2 O5 (80Si15Ca5P) mesoporous bioactive glass (MBG) sol. The procedure
      successfully produced consolidated and functionally competent open-cell scaffolds
      while preserving the nanoporous order of the SP. Scaffolds were prepared using
      four different (MBG)/(SP) ratios. These structures were then characterized using
      field emission gun scanning electron microscopy, X-ray diffraction (XRD),
      nitrogen adsorption-desorption measurements, and compressive strength testing.
      Open-cell interconnected structures with dual macro (150-500 MUm) and nano (4-6
      nm)-organised porosity were produced. Both the textural and mechanical properties
      were found to improve with increasing SBA-15 content. The in vitro bioactive
      response using simulated body fluid confirmed high reactivity for all prepared
      scaffolds. In addition, the SBA-15 containing scaffolds exhibited a superior
      ability to delay the pH-triggered lysozyme release with antibiotic activity.

PMID- 24123841
TI  - Enzymes from the haloacid dehalogenase (HAD) superfamily catalyse the elusive
      dephosphorylation step of riboflavin biosynthesis.
AB  - The missing link: Studies on the biosynthesis of riboflavin have failed to
      characterise dephosphorylation of the intermediate 5-amino-6-ribitylamino
      2,4(1H,3H)-pyrimidinedione 5'-phosphate. We show that this reaction can be
      catalysed in Escherichia coli by YigB and YbjI and in plant chloroplasts by
      AtcpFHy1, which are members of the haloacid dehalogenase superfamily. 

PMID- 24123842
TI  - Association study of 83 candidate genes for bipolar disorder in chromosome 6q
      selected using an evidence-based prioritization algorithm.
AB  - BACKGROUND: Prior genome-scans of bipolar disorder have revealed chromosome 6q22
      as a promising candidate region. However, linkage disequilibrium (LD) mapping
      studies have yet to identify replicated susceptibility loci. METHODS: We analyzed
      1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test
      single-marker and locus-wide evidence of association with bipolar disorder in the
      NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection
      (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated
      significant evidence of linkage to 6q. SNPs were genotyped using an Illumina
      iSelect genotyping array which employs the Infinium assay. Evidence of single
      marker association was assessed using the generalized disequilibrium test (GDT).
      Empirical estimates of gene-wide significance were obtained by permutation (via
      100,000 gene-dropping simulations) of Fisher's combined test of P-values for each
      locus. RESULTS: No single variant yielded significant experiment-wide evidence of
      association, for either the combined sample or in each subsample. Our gene
      dropping simulations identified nominally significant gene-wide associations with
      multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the
      strongest candidates. However, no one gene consistently exceeded empirical
      significance criteria in both independent samples or survived Bonferroni
      correction for the number of genes tested. CONCLUSIONS: Using a gene-based
      approach to family-based association, we identified gene-wide associations with
      several genes, though no single locus was significantly associated with bipolar
      disorder in both cohorts. This suggests that chromosome 6q may harbor multiple
      susceptibility loci or that complex patterns of LD in this region may confound
      approaches based on common SNPs. Published 2013. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 24123843
TI  - Gold-catalyzed tandem cycloisomerization and dimerization of chiral homopropargyl
      sulfonamides.

PMID- 24123844
TI  - A case for early bronchoscopic airway assessment after disc battery ingestion.
AB  - Disc battery ingestion in children is becoming increasingly common with the
      proliferation of small battery-powered electronic devices. In the case of
      esophageal impaction, the likelihood and severity of complications are
      proportionate to the time between ingestion and removal. Tracheo-esophageal
      fistulae (TOF) are a recognized complication and can be life-threatening. We
      describe an interesting case of disc battery ingestion with delayed recognition
      of a TOF. We document the tracheal mucosal healing process of a large airway
      defect and describe the role of bronchoscopy in guiding the timing of surgical
      intervention. This case highlights the important role of early bronchoscopic
      assessment in management of these patients.

PMID- 24123846
TI  - beta-Actin knock-out mouse embryonic fibroblasts show increased expression of LIM
      , CH-, EFh-domain containing proteins with predicted common upstream regulators.
AB  - beta-actin depletion from mouse embryonic fibroblasts results in an altered
      transcriptional response rendering these cells a myofibroblast like phenotype.
      The proteins and upstream regulatory factors responsible for this acquired
      phenotype, with prominent focal adhesions and stress fibres, are unknown. Data
      mining of the changed proteome revealed that actin binding proteins associated
      with stress fiber or focal adhesion formation are overexpressed in the beta-actin
      knock-out cells and that many of these contain CH-, LIM- or EFh- domains.
      Furthermore in silico analysis predicts potential common upstream regulators that
      may, at least partly, coordinate the altered transcriptional response.

PMID- 24123845
TI  - Characteristics associated with suppression of spermatogenesis in a male hormonal
      contraceptive trial using testosterone and Nestorone((r)) gels.
AB  - Development of a male hormonal contraceptive has been challenging ascribable to
      the failure to adequately suppress spermatogenesis in 5-10% of men. Methods to
      identify incomplete suppressors early in treatment might identify men most
      responsive to male hormonal contraceptives. We hypothesized that serum hormone
      and gonadotropin concentrations after 4 weeks of transdermal treatment with
      testosterone and Nestorone in a contraceptive trial would be associated with
      suppression of sperm concentrations to <1 million/mL after 24 weeks. Indeed,
      luteinizing hormone or follicle-stimulating hormone concentrations greater than 1
      IU/L after 4 weeks of transdermal testosterone/nestorone treatment were 97%
      sensitive for predicting failure to suppress spermatogenesis after 24 weeks of
      treatment. Serum nestorone concentrations were significantly associated with
      suppression, but serum testosterone concentrations were not. Early suppression of
      gonadotropins is associated with, but does not ensure, adequate suppression of
      spermatogenesis. This information may allow for rapid identification of non
      responders in male hormonal contraceptive trials. 

PMID- 24123847
TI  - Favorable outcome of patients affected by rhabdoid tumors due to rhabdoid tumor
      predisposition syndrome (RTPS).
AB  - Rhabdoid tumor predisposition syndrome is usually associated with shorter
      survival in patients with malignant rhabdoid tumors regardless of anatomical
      origin. Here we present four children harboring truncating heterozygous
      SMARCB1/INI1 germline mutations with favorable outcome. All four patients
      received multi-modality treatment, three according to therapeutic recommendations
      by the EU-RHAB registry, two without radiotherapy, and mean event-free survival
      accounts for 7 years. In conclusion, intensive treatment with curative intent is
      justified for children with rhabdoid tumors even if an underlying rhabdoid
      predisposition syndrome is demonstrated.

PMID- 24123848
TI  - Expanding the genotype-phenotype correlation in subtelomeric 19p13.3
      microdeletions using high resolution clinical chromosomal microarray analysis.
AB  - Structural rearrangements of chromosome 19p are rare, and their resulting
      phenotypic consequences are not well defined. This is the first study to report a
      cohort of eight patients with subtelomeric 19p13.3 microdeletions, identified
      using clinical chromosomal microarray analysis (CMA). The deletion sizes ranged
      from 0.1 to 0.86 Mb. Detailed analysis of the patients' clinical features has
      enabled us to define a constellation of clinical abnormalities that include
      growth delay, multiple congenital anomalies, global developmental delay, learning
      difficulties, and dysmorphic facial features. There are eight genes in the
      19p13.3 region that may potentially contribute to the clinical phenotype via
      haploinsufficiency. Moreover, in silico genomic analysis of 19p13.3 microdeletion
      breakpoints revealed numerous highly repetitive sequences, suggesting LINEs/SINEs
      mediated events in generating these microdeletions. Thus, subtelomeric 19p13.3
      appears important for normal embryonic and childhood development. The clinical
      description of patients with deletions in this genomic interval will assist
      clinicians to identify and treat individuals with similar deletions.

PMID- 24123849
TI  - Steroid-induced diabetes: a clinical and molecular approach to understanding and
      treatment.
AB  - Since the advent of glucocorticoid therapy for autoimmune disease in the 1940s,
      their widespread application has led to the concurrent therapy-limiting discovery
      of many adverse metabolic side effects. Unanticipated hyperglycemia associated
      with the initiation of glucocorticoids often leads to preventable hospital
      admissions, prolonged hospital stays, increased risks for infection and reduced
      graft function in solid organ transplant recipients. Challenges in managing
      steroid-induced diabetes stem from wide fluctuations in post-prandial
      hyperglycemia and the lack of clearly defined treatment protocols. The mainstay
      of treatment is insulin therapy coincident with meals. This article aims to
      review the pathogenesis, risk factors, diagnosis and treatment principles unique
      to steroid-induced diabetes.

PMID- 24123850
TI  - Capillary electrophoresis analysis of conventional splicing assays: IARC
      analytical and clinical classification of 31 BRCA2 genetic variants.
AB  - Rare sequence variants in "high-risk" disease genes, often referred as
      unclassified variants (UVs), pose a serious challenge to genetic testing.
      However, UVs resulting in splicing alterations can be readily assessed by in
      vitro assays. Unfortunately, analytical and clinical interpretation of these
      assays is often challenging. Here, we explore this issue by conducting splicing
      assays in 31 BRCA2 genetic variants. All variants were assessed by RT-PCR
      followed by capillary electrophoresis and direct sequencing. If assays did not
      produce clear-cut outputs (Class-2 or Class-5 according to analytical
      International Agency for Research on Cancer guidelines), we performed qPCR and/or
      minigene assays. The latter were performed with a new splicing vector (pSAD)
      developed by authors of the present manuscript (patent #P201231427 CSIC). We have
      identified three clinically relevant Class-5 variants (c.682-2A>G, c.7617+1G>A,
      and c.8954-5A>G), and 27 analytical Class-2 variants (not inducing splicing
      alterations). In addition, we demonstrate that rs9534262 (c.7806-14T>C) is a
      BRCA2 splicing quantitative trait locus. 

PMID- 24123851
TI  - Rapid, stable, chemoselective labeling of thiols with Julia-Kocienski-like
      reagents: a serum-stable alternative to maleimide-based protein conjugation.

PMID- 24123852
TI  - "No one really knows why they are alive until they know what they'd die for":
      lessons from the death of a living liver donor.

PMID- 24123854
TI  - Microelectrode electrochemistry with semiconducting microelectrode chips.
AB  - Well-defined semiconducting microelectrodes on silicon chips are prepared for new
      insights into microelectrode electrochemistry. Unique voltammetric features are
      observed due to a combined effect of enhanced mass transport from microelectrodes
      and rectifying nature of the semiconductor-electrolyte interface. The
      "diffusional independence" of single elements in certain arrays is also carefully
      studied. 

PMID- 24123853
TI  - Inhibition of repulsive guidance molecule, RGMa, increases afferent synapse
      formation with auditory hair cells.
AB  - The peripheral fibers that extend from auditory neurons to hair cells are
      sensitive to damage, and replacement of the fibers and their afferent synapse
      with hair cells would be of therapeutic interest. Here, we show that RGMa, a
      repulsive guidance molecule previously shown to play a role in the development of
      the chick visual system, is expressed in the developing, newborn, and mature
      mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons
      and hair cells, from which afferent connections had been removed, was assessed.
      Contact of neural processes with hair cells and elaboration of postsynaptic
      densities at sites of the ribbon synapse were increased by treatment with a
      blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature
      branching pattern of afferent neurons was accelerated. Inhibition by RGMa could
      thus explain why auditory neurons have a low capacity to regenerate peripheral
      processes: postnatal spiral ganglion neurons retain the capacity to send out
      processes that respond to signals for synapse formation, but expression of RGMa
      postnatally appears to be detrimental to regeneration of afferent hair cell
      innervation and antagonizes synaptogenesis. Increased synaptogenesis after
      inhibition of RGMa suggests that manipulation of guidance or inhibitory factors
      may provide a route to increase formation of new synapses at deafferented hair
      cells.

PMID- 24123856
TI  - Refining spectral library searching.
AB  - Spectral library searching has many advantages over sequence database searching,
      yet it has not been widely adopted. One possible reason for this is that users
      are unsure exactly how to interpret the similarity scores (e.g., "dot products"
      are not probability-based scores). Methods to create decoys have been proposed,
      but, as developers caution, may produce proxies that are not equivalent to
      reversed sequences. In this issue, Shao et al. (Proteomics 2013, 13, 3273-3283)
      report advances in spectral library searching where the focus is not on improving
      the performance of their search engine, SpectraST, but is instead on improving
      the statistical meaningfulness of its discriminant score and removing the need
      for decoys. The results in their paper indicate that by "standardizing" the input
      and library spectra, sensitivity is not lost but is, surprisingly, gained. Their
      tests also show that false discovery rate (FDR) estimates, derived from their new
      score, track better with "ground truth" than decoy searching. It is possible that
      their work strikes a good balance between the theory of library searching and its
      application. And as such, they hope to have removed a major entrance barrier for
      some researchers previously unwilling to try library searching. 

PMID- 24123855
TI  - Mutant monocyte chemoattractant protein 1 protein attenuates migration of and
      inflammatory cytokine release by macrophages exposed to orthopedic implant wear
      particles.
AB  - Wear particles generated from total joint replacements can stimulate macrophages
      to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which
      is the most important chemokine regulating systemic and local cell trafficking
      and infiltration of monocyte/macrophages in chronic inflammation. One possible
      strategy to curtail the adverse events associated with wear particles is to
      mitigate migration and activation of monocyte/macrophages. The purpose of this
      study is to modulate the adverse effects of particulate biomaterials and
      inflammatory stimuli such as endotoxin by interfering with the biological effects
      of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited
      by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C
      chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP-1
      induced migration of THP-1 cells in cell migration experiments in a dose
      dependent manner. Conditioned media from murine macrophages exposed to clinically
      relevant polymethylmethacrylate (PMMA) particles with/without endotoxin
      [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which
      was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the
      viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to
      form bone at the doses tested. Finally, proinflammatory cytokine production was
      mitigated when macrophages were exposed to PMMA particles with/without LPS in the
      presence of 7ND. Our studies confirm that the MCP-1 mutant protein 7ND can
      decrease macrophage migration and inflammatory cytokine release without adverse
      effects at the doses tested. Local delivery of 7ND at the implant site may
      provide a therapeutic strategy to diminish particle-associated periprosthetic
      inflammation and osteolysis.

PMID- 24123857
TI  - Gender-related sensitivity of development and growth to real microgravity in
      Xenopus laevis.
AB  - Exposure of organisms to microgravity can induce morphological, physiological,
      and behavioral modifications which normalize after re-entry in 1g-condition
      within hours to few weeks. Development of Xenopus laevis tadpoles, their
      metamorphosis, and adults' growth were monitored for 3 years after their flight
      on the 12-day Soyuz mission TMA13 to the International Space Station. At onset of
      microgravity, tadpoles had just developed the hind limb (stage 47) or forelimb
      bud (stage 50). Recordings during the first 4 days after landing revealed no
      differences of developmental progresses and growth between flight and ground
      tadpoles. Further development and growth were strongly retarded in all animals;
      nevertheless, significant differences appeared between flight and ground groups
      during this postflight period. They include (1) acceleration of development in
      stage 47 but not stage 50 flight tadpoles; (2) earlier metamorphosis of stage 47
      flight tadpoles compared to their 1g-ground controls while stage 50 flight
      tadpoles metamorphosed later than their ground controls; (3) maintenance of a
      tail during the juvenile stage exclusively in some stage 47 flight animals, and
      (4) accelerated growth of stage 47 male flight toads but retarded growth of stage
      50 flight males compared to the respective 1g-ground control males. No difference
      of growth was detected between flight and ground females after metamorphosis. All
      differences between flight and ground animals disappeared 1 year after landing.
      We conclude (1) that limited spatial and nutritional conditions during the
      mission period caused developmental retardation, and (2) that the thyroid gland
      of Xenopus is susceptible to spatial environment, in particular, during the
      period of beginning activation.

PMID- 24123858
TI  - Self-assembled apatite on multiwalled carbon nanotubes substrates support
      osteogenic cell function.
AB  - The properties of multiwalled carbon nanotubes (MWCNT) make them attractive for
      use in biological matrices, especially in the development of bone-like materials.
      However, their inherent hydrophobicity is a factor that has impeded broader use.
      A simple, novel method for coating MWCNT in apatite was developed and evaluated
      to enable their use in tissue engineering. This apatite coating was deposited on
      the nanotubes (which had been embedded in high-density polyethylene) and
      facilitated the growth and differentiation of osteoblasts in a manner comparable
      to that of traditional tissue culture surfaces. Different levels of MWCNT purity
      (>90 and >95%) and chemical functionalization (carboxylation) were found to be
      amenable to deposition of an apatite coating and subsequent cell culture. The
      modalities evaluated were cell metabolic activity (MTS assay), cell proliferation
      (CyQuant assay), and cell differentiation (alkaline phosphatase assay); release
      of lactate dehydrogenase provided an indication of cytotoxicity. Although broadly
      comparable to traditional tissue culture surfaces, the carboxyl-functionalized
      surfaces were associated with lower levels of growth and differentiation. The
      noncarboxylated surfaces proved to be broadly comparable to tissue culture
      plastic in terms of cell function. Therefore, apatite-coated MWCNT provide a
      surface capable of supporting osteogenic cells.

PMID- 24123859
TI  - Validity and reliability of Patient Health Questionnaire-9 and Patient Health
      Questionnaire-2 to screen for depression among college students in China.
AB  - INTRODUCTION: This study examined the validity and reliability of the Patient
      Health Questionnaire-9 (PHQ-9) and Patient Health Questionnaire-2 (PHQ-2). The
      optimal cutoff score when screening for depression among Chinese college students
      was also determined. METHODS: A total of 959 participants completed the PHQ-9 and
      the Beck Depression Inventory (BDI) questionnaire. The Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders was used to
      diagnose depression. Statistical tests were performed to determine the
      reliability, validity, and receiver operating characteristic curve of the data.
      The concurrent validity was tested by examining associations between PHQ-9 and
      BDI. The sensitivity and specificity, as well as the positive and negative
      predictive values, were calculated for different cutoff scores of PHQ-9 and PHQ
      2. RESULTS: The internal consistency values of PHQ-9 and PHQ-2 were 0.854 and
      0.727, respectively. The test-retest reliability values of PHQ-9 and PHQ-2 were
      0.873 and 0.829, respectively. The scores of PHQ-9 (r = 0.790) and PHQ-2 (r =
      0.651) were significantly associated with that of BDI. PHQ-9 had an optimal
      cutoff score of 11, which indicated a sensitivity of 0.89 and a specificity of
      0.97, with an area under the curve of 0.977 (95% confidence interval: 0.966
      0.988). The PHQ-2 demonstrated satisfactory sensitivity (0.81) and specificity
      (0.96) at the cutoff score of 3, and its area under the curve was 0.939.
      DISCUSSION: The PHQ-9 and the PHQ-2 are valid and reliable tools to screen
      depression in Chinese college students. For screening purposes, cutoff scores of
      11 and 3 are recommended for PHQ-9 and PHQ-2, respectively.

PMID- 24123860
TI  - Simultaneous quantification of energetically important metabolites in various
      cell types by CZE.
AB  - A new CZE method was developed for the determination of 12 purine and pyrimidine
      nucleotides, two adenine coenzymes and their reduced forms, and acetyl coenzyme A
      in various cell extracts. As the concentration levels of these metabolites in
      living cells are low; CZE was combined with field-enhanced sample stacking. As a
      result, the separation conditions were optimised to achieve a suitable resolution
      at the relatively high sample volume provided by this on-line pre-concentration
      technique. The optimum BGE was 150 mM glycine buffer (pH 9.5). Samples were
      introduced hydrodynamically using a pressure of 35 mbar (3.5 kPa) for 25 s, and
      data were collected at a detection wavelength of 260 nm. An applied voltage of 30
      kV (positive polarity) and capillary temperature of 25 degrees C gave the best
      separation of these compounds. The optimised method was validated by determining
      the linearity, sensitivity and repeatability and it was successfully applied for
      the analysis of extracts from Paracoccus denitrificans bacteria and from stem
      cells. 

PMID- 24123861
TI  - A supramolecular gel from a quadruple zwitterion that responds to both acid and
      base.

PMID- 24123862
TI  - Resonance light scattering determination of trace bisphenol A with signal
      amplification by aptamer-nanogold catalysis.
AB  - HAuCl4 was reduced by sodium citrate to prepare 10 nm gold nanoparticles (AuNPs)
      that were modified by the bisphenol A aptamer (Apt) to obtain an aptamer-nanogold
      probe (Apt-AuNP) for bisphenol A (BPA). The probes were aggregated
      nonspecifically to form large clusters, which showed a strong resonance light
      scattering (RLS) peak at 520 nm, under preparation conditions (pH 7.6 Na2HPO4
      NaH2PO4 buffer and ultrasonication). Upon addition of BPA, the probe reacted
      specifically to form dispersed BPA-Apt-AuNP conjugates that exhibited strong
      catalysis of the two particle reactions of glucose-Cu(II) and hydrazine
      hydrochloride-Cu(II) with a strong RLS peak at 360 nm and 510 nm respectively.
      When the BPA concentration increased, the RLS intensity at 360 nm and 510 nm
      increased respectively. Accordingly, two new and highly-sensitive RLS methods
      were established for the detection of BPA, using the Apt-AuNP catalytic
      amplification.

PMID- 24123863
TI  - The conformation of the prion domain of Sup35p in isolation and in the full
      length protein.

PMID- 24123864
TI  - The association between TNF-alpha and erectile dysfunction complaints.
AB  - Inflammatory markers like tumour necrosis factor-alpha (TNF-alpha) have been
      related to erectile dysfunction (ED) and may interact with other cardiovascular
      risk factors such as obstructive sleep apnoea syndrome (OSAS). The aim of this
      study was to examine the inflammatory, metabolic and hormonal profile of men with
      or without ED complaints and/or OSAS recruited through the Epidemiologic Sleep
      Study (EPISONO). A sample of 363 men completed sexual questionnaires for ED and
      had physical and blood examinations. OSAS was evaluated by polysomnography and
      clinical assessment. The blood samples were used for determination of TNF-alpha,
      interleukin-6, leptin, cholesterol and fractions, triglycerides, homocysteine,
      glucose and hormonal levels. After controlling for confounding factors, men with
      ED complaints presented higher systolic blood pressure and TNF-alpha, independent
      of OSAS. Significant interaction between ED and OSAS was only observed for neck
      circumference, which was higher in ED men with OSAS than men with OSAS without ED
      and men with ED without OSAS. Binary logistic regression showed that the
      predictor factors for ED were age >43 years, myocardial infarction events, TNF
      alpha and systolic blood pressure. Finally, a receiver-operating characteristics
      curve suggested a cut-off point of 9.95 pg/mL for TNF-alpha with sensitivity of
      60% and specificity of 59% in men with ED complaints. Furthermore, there was a
      significant association between high levels of TNF-alpha (>9.95 pg/mL) and the
      presence of ED complaints. The results showed that there was an association
      between TNF-alpha levels and ED complaints in men independent of OSAS. 

PMID- 24123865
TI  - A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in
      children with recurrent or progressive cancer.
AB  - BACKGROUND: Preclinical models show that an antiangiogenic regimen at low-dose
      daily (metronomic) dosing may be effective against chemotherapy-resistant tumors.
      We undertook a prospective, open-label, single-arm, multi-institutional phase II
      study to evaluate the efficacy of a "5-drug" oral regimen in children with
      recurrent or progressive cancer. PROCEDURE: Patients <=21 years old with
      recurrent or progressive tumors were eligible. Treatment consisted of continuous
      oral celecoxib, thalidomide, and fenofibrate, with alternating 21-day cycles of
      low-dose cyclophosphamide and etoposide. Primary endpoint was to assess, within
      eight disease strata, activity of the 5-drug regimen over 27 weeks. Blood and
      urine angiogenesis markers were assessed. RESULTS: One hundred one patients were
      enrolled; 97 began treatment. Median age was 10 years (range: 191 days-21 years);
      47 (49%) were female. Disease strata included high-grade glioma (HGG, 21
      patients), ependymoma (19), low-grade glioma (LGG, 12), bone tumors (12),
      medulloblastoma/primitive neuroectodermal tumor (PNET, 8), leukemia (4),
      neuroblastoma (3), and miscellaneous tumors (18). Treatment was generally well
      tolerated; most common toxicities were hematologic. Twenty-four (25%) patients
      completed 27 weeks therapy without progression, including HGG: 1 (5%),
      ependymoma: 7 (37%), LGG: 7 (58%), medulloblastoma/PNET: 1, neuroblastoma: 1, and
      miscellaneous tumors: 7 (39%). Best response was complete response (one patient
      with medulloblastoma), partial response (12), stable disease (36), progressive
      disease (47), and inevaluable (1). Baseline serum thrombospondin levels were
      significantly higher in patients successfully completing therapy than in those
      who progressed (P = 0.009). CONCLUSION: The 5-drug regimen was well tolerated.
      Clinical activity was demonstrated in some but not all tumor strata.

PMID- 24123867
TI  - We need to improve screening for sexually transmitted infections in men who have
      sex with men in Europe.

PMID- 24123868
TI  - Audit unlocked.

PMID- 24123866
TI  - WHO guidelines for HIV/STI prevention and care among MSM and transgender people:
      implications for policy and practice.

PMID- 24123869
TI  - Chlamydia testing: where are we now? Recruiting high-risk women to a pilot STI
      screening trial.

PMID- 24123870
TI  - Universal perinatal screening for Treponema pallidum: the role of a dedicated
      infectious diseases team for prevention of mother-to-child transmission.

PMID- 24123871
TI  - Gonorrhoea surveillance in Ghana, Africa.

PMID- 24123873
TI  - Endoscopic papillary large-balloon dilation versus endoscopic papillary regular
      balloon dilation for removal of large bile-duct stones.
AB  - BACKGROUND: Endoscopic papillary large-balloon dilation (EPLBD) became popular
      for the treatment of large common bile-duct stones (CBDS), and its feasibility
      has been reported in comparison to endoscopic sphincterotomy. However, the
      comparison between EPLBD and endoscopic papillary regular-balloon dilation (EPBD)
      has not been reported. In the present study, the efficacy and complications of
      EPLBD were compared with those of EPBD. METHODS: We retrospectively assessed 334
      consecutive patients with CBDS of any size that were treated by either EPLBD or
      EPBD between January 2008 and December 2012. RESULTS: In cases with large CBDS
      (>10 mm), EPLBD and EPBD had similar results in terms of the success rate of
      stone removal in the first (65% vs. 84%) and total attempts (100% vs. 95%), use
      of mechanical lithotripter (64% vs. 80%), and procedure time (48.0 +/- 17.8 min
      vs. 44.1 +/- 17.1 min). The necessity for crushing stones with a mechanical
      lithotripter was significantly decreased in EPLBD compared to EPBD (25% vs. 80%).
      In all cases with CBDS, there was no significant difference in complication rates
      between EPLBD and EPBD (3.3% vs. 4.7%). CONCLUSIONS: Compared to EPBD, EPLBD
      appears safe and effective for removing large CBDS and decreases the necessity of
      lithotripsy.

PMID- 24123875
TI  - Somatic point mutations occurring early in development: a monozygotic twin study.
AB  - The identification of somatic driver mutations in cancer has enabled therapeutic
      advances by identifying drug targets critical to disease causation. However, such
      genomic discoveries in oncology have not translated into advances for non
      cancerous disease since point mutations in a single cell would be unlikely to
      cause non-malignant disease. An exception to this would occur if the mutation
      happened early enough in development to be present in a large percentage of a
      tissue's cellular population. We sought to identify the existence of somatic
      mutations occurring early in human development by ascertaining base-pair
      mutations present in one of a pair of monozygotic twins, but absent from the
      other and assessing evidence for mosaicism. To do so, we genome-wide genotyped 66
      apparently healthy monozygotic adult twins at 506 786 high-quality single
      nucleotide polymorphisms (SNPs) in white blood cells. Discrepant SNPs were
      verified by Sanger sequencing and a selected subset was tested for mosaicism by
      targeted high-depth next-generation sequencing (20 000-fold coverage) as a
      surrogate marker of timing of the mutation. Two de novo somatic mutations were
      unequivocally confirmed to be present in white blood cells, resulting in a
      frequency of 1.2*10(-7) mutations per nucleotide. There was little evidence of
      mosaicism on high-depth next-generation sequencing, suggesting that these
      mutations occurred early in embryonic development. These findings provide direct
      evidence that early somatic point mutations do occur and can lead to differences
      in genomes between otherwise identical twins, suggesting a considerable burden of
      somatic mutations among the trillions of mitoses that occur over the human
      lifespan.

PMID- 24123877
TI  - Hemodynamic changes in the hepatic circulation after the modulation of the
      splenic circulation in an in vivo human experimental model.
AB  - Recent advances in liver surgery have highlighted the effects of the splenic
      circulation on the hepatic circulation with respect to the hepatic arterial
      buffer response (HABR). The aim of the present study was to investigate the
      actual hemodynamic effects of splenic artery embolization/ligation and
      splenectomy on the hepatic circulation in patients who underwent
      pancreaticoduodenectomy through in vivo experimental models. In vivo models of
      splenic artery embolization/ligation (only splenic artery clamping) and
      splenectomy (simultaneous clamping of both the splenic artery and the splenic
      vein) were created in 40 patients who underwent pancreaticoduodenectomy for
      various reasons. The portal venous flow velocity, the portal venous flow volume,
      the hepatic arterial flow velocity, and the hepatic arterial resistance index
      were measured with color Doppler ultrasonography. Clamping of the splenic artery
      induced an immediate and significant increase (16%) in the hepatic artery
      velocity (P < 0.001), and the portal venous flow also decreased significantly
      (10%, P = 0.03). Fifteen minutes after the clamping of the splenic artery, the
      hepatic artery velocity remained significantly increased at the level of the
      initial clamping, and the portal venous flow significantly decreased (16%, P <
      0.001). Clamping of the splenic vein, which was performed after the clamping of
      the splenic artery, resulted in an immediate and significant decrease (30%) in
      the portal venous flow (P < 0.001), but the hepatic arterial flow was not
      affected. Fifteen minutes after the clamping of the splenic vein, there was no
      change in the portal flow, which remained significantly lower (28%) than the flow
      in controls, whereas the hepatic arterial flow further significantly increased
      (31%, P < 0.001). In conclusion, our findings indicate that both splenic artery
      embolization/ligation and splenectomy are effective for increasing hepatic
      arterial flow and decreasing portal flow, with splenectomy providing a greater
      advantage. The HABR underlies these hemodynamic changes.

PMID- 24123876
TI  - Identification of pathogenic gene variants in small families with intellectually
      disabled siblings by exome sequencing.
AB  - BACKGROUND: Intellectual disability (ID) is a common neurodevelopmental disorder
      affecting 1-3% of the general population. Mutations in more than 10% of all human
      genes are considered to be involved in this disorder, although the majority of
      these genes are still unknown. OBJECTIVES: We investigated 19 small non
      consanguineous families with two to five affected siblings in order to identify
      pathogenic gene variants in known, novel and potential ID candidate genes. Non
      consanguineous families have been largely ignored in gene identification studies
      as small family size precludes prior mapping of the genetic defect. METHODS AND
      RESULTS: Using exome sequencing, we identified pathogenic mutations in three
      genes, DDHD2, SLC6A8, and SLC9A6, of which the latter two have previously been
      implicated in X-linked ID phenotypes. In addition, we identified potentially
      pathogenic mutations in BCORL1 on the X-chromosome and in MCM3AP, PTPRT, SYNE1,
      and ZNF528 on autosomes. CONCLUSIONS: We show that potentially pathogenic gene
      variants can be identified in small, non-consanguineous families with as few as
      two affected siblings, thus emphasising their value in the identification of
      syndromic and non-syndromic ID genes.

PMID- 24123874
TI  - The XY gene hypothesis of psychosis: origins and current status.
AB  - Sex differences in psychosis and their interaction with laterality (systematic
      departures from 50:50 left-right symmetry across the antero-posterior neural
      axis) are reviewed in the context of the X-Y gene hypothesis. Aspects of
      laterality (handedness/cerebral asymmetry/the torque) predict (1) verbal and non
      verbal ability in childhood and across adult life and (2) anatomical,
      physiological, and linguistic variation relating to psychosis. Neuropsychological
      and MRI evidence from individuals with sex chromosome aneuploidies indicates that
      laterality is associated with an X-Y homologous gene pair. Within each mammalian
      species the complement of such X-Y gene pairs reflects their potential to account
      for taxon-specific sexual dimorphisms. As a consequence of the mechanism of
      meiotic suppression of unpaired chromosomes <MSUC> such X-Y gene pairs generate
      epigenetic variation around a species defining motif that is carried to the
      zygote with potential to initiate embryonic gene expression in XX or XY format.
      The Protocadherin11XY (PCDH11XY) gene pair in Xq21.3/Yp11.2 in probable
      coordination with a gene or genes within PAR2 (the second pseudo-autosomal
      region) is the prime candidate in relation to cerebral asymmetry and psychosis in
      Homo sapiens. The lately-described pattern of sequence variation associated with
      psychosis on the autosomes may reflect a component of the human genome's
      adjustment to selective pressures generated by the sexually dimorphic mate
      recognition system.

PMID- 24123878
TI  - Dissociation kinetics of a binary complex in solution by protein displacement.

PMID- 24123879
TI  - High-strength poly(para-phenylene) as an orthopedic biomaterial.
AB  - Poly(para-phenylene) (PPP) exhibits exceptional mechanical strength, stiffness,
      toughness, and chemical inertness, although it is not currently used in any
      biomedical applications. The purpose of this study is to serve as a preliminary
      investigation into the potential of PPP as a biomaterial in orthopedic load
      bearing applications. Nuclear magnetic resonance (NMR) analysis confirmed a
      polymer structure composed of an aromatic backbone and side groups. Tensile PPP
      specimens along with samples from several other polymers often used for
      orthopedic applications were elongated to failure after being soaked in phosphate
      buffered saline (PBS) for 1 h, 1 day, 1 week, 2 weeks, 1 month, and more than 1
      year. Results showed that PBS absorption of the PPP plateaued at 1 week at values
      of ~0.7 wt % and remained within one standard deviation when soaked for over 1
      year. PBS absorption did not affect elastic modulus (5.0 GPa), yield strength
      (141 MPa), fracture strength (120 MPa) and strain-to-failure (17%) more than one
      standard deviation. Zero-to-tension fatigue testing established an endurance
      limit of approximately 35 MPa, which was relatively insensitive to frequency (1
      10 Hz). Eagle's minimum essential medium (MEM) elution assay with fibroblasts
      confirmed that the PPP was noncytotoxic. Relative to other polymers used for load
      bearing biomedical applications, PPP displays promising mechanical properties
      that remain stable in aqueous solution. Lastly, prototype PPP and
      polyetheretherketone (PEEK) bone plates were manufactured and tested, with the
      PPP plate showing a 38% higher maximum tensile load before failure.

PMID- 24123885
TI  - Perspectives on RAGE signaling and its role in cardiovascular disease.
AB  - RAGE stands for Receptor of Advanced Glycation Endproducts. The two main topics
      discussed are (1) the nature of RAGE signaling and (2) its role in cardiovascular
      disease. RAGE may occur in membrane-bound form or in secretory form. RAGE
      signaling involves multiple ligands: (1) several AGEs (2) amyloid beta pecursor
      protein (APP), (3) high mobility group box 1 (HMGB1), (4) S100A4, (5) S100A8/A9,
      and (6) S100A12, which are calcium-binding proteins, and (7) S100B, a glial
      derived protein. RAGE ligands and various diseases involving RAGE signaling are
      summarized in tabular form.

PMID- 24123880
TI  - Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive paralysis due to the selective death of motor
      neurons of unknown causes. Increasing evidence indicates that Wnt signaling is
      altered in ALS. In this study, we focused on two non-canonical Wnt signaling
      components, atypical PKC (aPKC) and a Wnt receptor, Ryk, in a mouse model of ALS,
      SOD1 (G93A). aPKC mediates Wnt signaling to regulate growth cone guidance, axon
      differentiation and cell survival. Ryk is a Wnt repulsive receptor that regulates
      axon guidance and inhibits regeneration after spinal cord injury. aPKC expression
      was increased in motor neurons of the lumbar spinal cord in SOD1 (G93A) mice at
      both early and late stages. Interestingly, aPKC was co-localized with SOD1 in
      motor neuron cell bodies and extracellular aggregates, and aPKC-containing
      extracellular aggregates increased with disease progression. Biochemical
      fractionation showed that aPKC protein level was increased in the detergent
      insoluble protein fraction in SOD1 (G93A) mice at late stage but decreased in the
      detergent-soluble fraction at symptomatic stage. These results suggest that aPKC
      may be sequestered in SOD1 aggregates, impairing its ability to protect motor
      neurons from death. Ryk expression was also increased in the motor neurons and
      the white matter in the ventral lumbar spinal cord of mutant SOD1 mice with a
      peak at early stage. These observations indicate that Wnt/aPKC and Wnt/Ryk
      signaling are altered in SOD1 (G93A) mice, suggesting that changed Wnt signaling
      may contribute to neurodegeneration in ALS.

PMID- 24123886
TI  - Purification of hen egg white ovomacroglobulin using one-step chromatography.
AB  - Hen egg white (EW) are one of the most ideal sources of active proteins, and
      ovomacroglobulin, as a protease inhibitor, has been demonstrated to possess
      numerous biological properties including antibacterial and anti-inflammatory
      properties as well as activity for the treatment of keratitis. The objective of
      this study was to develop a simple and rapid method for the purification of
      ovomacroglobulin from hen EW on a laboratory scale. Hen EW was diluted with an
      equal volume of distilled water followed by a two-step PEG precipitation to
      remove ovomucin and to obtain ovomacroglobulin-rich precipitate. The precipitate
      was dissolved and further purified by gel filtration chromatography.
      Ovomacroglobulin was collected with a purity of 97.0 +/- 0.3% by HPLC and a yield
      of 62.5%. The atomic force microscopy images showed that ovomacroglobulin
      molecules on a mica surface emerged as an "oval-shaped plate" with a molecular
      volume of 1536.9 +/- 330.0 nm(3) , indicating that purified ovomacroglobulin has
      an integrated molecular structure. With the improvement of PEG precipitation and
      the simplification of the chromatography, the whole purification process could be
      finished well within one working day. This protocol has an advantage of rapidity,
      and would facilitate studies of ovomacroglobulin. 

PMID- 24123889
TI  - Oxidation sharpening, template stripping, and passivation of ultra-sharp metallic
      pyramids and wedges.
AB  - Ultra-sharp metallic pyramids and wedges with tunable tip angles and 5-nm tip
      radii are replicated from oxidation-sharpened silicon templates with high
      throughput (80 million pyramids per wafer). Atomic layer deposition of Al2 O3
      shells can protect these sharp pyramidal tips for subsequent usage in near-field
      imaging. 

PMID- 24123888
TI  - Impact of ethnicity and extreme prematurity on infant pulmonary function.
AB  - The impact of birth before 27 completed weeks of gestation on infant pulmonary
      function (PF) was explored in a multi-ethnic population in comparison to more
      mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung
      volume (FRCpleth ) and forced expired volume (FEV0.5 ) were obtained at ~12
      months post-term age in 52 extremely preterm (EP) infants (median [range]
      gestational age [GA]: 26 [23-27] weeks; 40% White mothers; 79% with BPD), 41 PTC
      (GA:35 [30-36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37-42]
      weeks; 86% White mothers). Using reference equations based on identical equipment
      and techniques, results were expressed as z-scores to adjust for age, sex and
      body size. FEV0.5 was significantly lower in EP infants when compared with PTC
      (mean difference [95% CI]: -1.02[-1.60; -0.44] z-scores, P < 0.001), as was
      forced vital capacity (FVC) but there were no significant differences in FRCpleth
      or FEV0.5 /FVC ratio. FEV0.5 , FVC, and FEV0.5 /FVC were significantly lower in
      both preterm groups when compared with fullterm controls. On multivariable
      analyses of the combined preterm dataset: FEV0.5 at ~1 year was 0.11 [0.05; 0.17]
      z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with
      prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores
      lower, with similar reductions in FVC, such that there were no ethnic differences
      in FEV0.5 /FVC. Similar ethnic differences were observed among fullterm infants.
      These results confirm the negative impact of preterm birth on subsequent lung
      development, especially following a diagnosis of BPD, and emphasize the
      importance of taking ethnic background into account when interpreting results
      during infancy as in older subjects.

PMID- 24123891
TI  - Formal ring-opening/cross-coupling reactions of 2-pyrones: iron-catalyzed entry
      into stereodefined dienyl carboxylates.
AB  - Open access: Despite the exceptional level of sophistication in cross-coupling
      chemistry, reactions of substrates that incorporate the leaving group as an
      integral part into a heterocyclic scaffold are scarce. The title reaction
      outlines the utility of this reaction format (see scheme; acac=acetylacetonate),
      provides a convenient entry into stereodefined diene carboxylates, and adds a new
      chapter to the field of iron catalysis. 

PMID- 24123887
TI  - Rule-based modeling: a computational approach for studying biomolecular site
      dynamics in cell signaling systems.
AB  - Rule-based modeling was developed to address the limitations of traditional
      approaches for modeling chemical kinetics in cell signaling systems. These
      systems consist of multiple interacting biomolecules (e.g., proteins), which
      themselves consist of multiple parts (e.g., domains, linear motifs, and sites of
      phosphorylation). Consequently, biomolecules that mediate information processing
      generally have the potential to interact in multiple ways, with the number of
      possible complexes and posttranslational modification states tending to grow
      exponentially with the number of binary interactions considered. As a result,
      only large reaction networks capture all possible consequences of the molecular
      interactions that occur in a cell signaling system, which is problematic because
      traditional modeling approaches for chemical kinetics (e.g., ordinary
      differential equations) require explicit network specification. This problem is
      circumvented through representation of interactions in terms of local rules. With
      this approach, network specification is implicit and model specification is
      concise. Concise representation results in a coarse graining of chemical
      kinetics, which is introduced because all reactions implied by a rule inherit the
      rate law associated with that rule. Coarse graining can be appropriate if
      interactions are modular, and the coarseness of a model can be adjusted as
      needed. Rules can be specified using specialized model-specification languages,
      and recently developed tools designed for specification of rule-based models
      allow one to leverage powerful software engineering capabilities. A rule-based
      model comprises a set of rules, which can be processed by general-purpose
      simulation and analysis tools to achieve different objectives (e.g., to perform
      either a deterministic or stochastic simulation).

PMID- 24123890
TI  - Genetic and functional analyses of ZIC3 variants in congenital heart disease.
AB  - Mutations in zinc-finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated
      congenital heart disease (CHD). The majority of reported mutations cluster in
      zinc-finger domains. We previously demonstrated that many of these lead to
      aberrant ZIC3 subcellular trafficking. A relative paucity of N- and C-terminal
      mutations has, however, prevented similar analyses in these regions. Notably, an
      N-terminal polyalanine expansion was recently identified in a patient with
      VACTERL, suggesting a potentially distinct function for this domain. Here we
      report ZIC3 sequencing results from 440 unrelated patients with heterotaxy and
      CHD, the largest cohort yet examined. Variants were identified in 5.2% of
      sporadic male cases. This rate exceeds previous estimates of 1% and has important
      clinical implications for genetic testing and risk-based counseling. Eight of 11
      were novel, including 5 N-terminal variants. Subsequent functional analyses
      included four additional reported but untested variants. Aberrant cytoplasmic
      localization and decreased luciferase transactivation were observed for all zinc
      finger variants, but not for downstream or in-frame upstream variants, including
      both analyzed polyalanine expansions. Collectively, these results expand the ZIC3
      mutational spectrum, support a higher than expected prevalence in sporadic cases,
      and suggest alternative functions for terminal mutations, highlighting a need for
      further study of these domains.

PMID- 24123892
TI  - Metal-free oxidative cyclization of alkynyl aryl ethers to benzofuranones.

PMID- 24123893
TI  - Elimination of apoptotic spermatozoa by magnetic-activated cell sorting improves
      the fertilization rate of couples treated with ICSI procedure.
AB  - Couples with unexplained infertility (UI) tend to have low fertilization rates
      using current in vitro fertilization procedures. The aim of this study was to
      evaluate whether elimination of apoptotic spermatozoa could increase the
      likelihood of pregnancy by intra-cytoplasmic sperm injection (ICSI). A total of
      74 couples with UI were divided into two groups including the control group (n =
      37) for which spermatozoa prepared by density gradient centrifugation were
      injected into oocytes and the study group (n = 37) for which spermatozoa was
      further processed by magnetic-activated cell sorting to eliminate apoptotic
      spermatozoa, then injected into oocytes. Fertilization, cleavage, pregnancy and
      birth rates were analyzed in two groups. The fertilization rate was significantly
      higher in the study group compared with the control group (73.41% vs. 61.11%; p =
      0.03). On day 3, the number of eight blastomeric non-fragmented embryos per
      oocytes was also significantly higher in study group as compared with controls
      (45.05% vs. 34.16%; p = 0.049). The pregnancy and birth rates were 43.24 and
      40.5% in study group and 35.11 and 27% in control group respectively. Statistical
      analyses showed that the differences in the pregnancy and live-birth rates
      between study and control groups were not significant (p = 0.37 and 0.16
      respectively). These results demonstrate that non-apoptotic spermatozoa display
      higher fertilization potential and embryo quality following ICSI. 

PMID- 24123894
TI  - Actin and microtubules play distinct roles in governing the anisotropic
      deformation of cell nuclei in response to substrate strain.
AB  - Physical forces arising in the cellular microenvironment have been hypothesized
      to play a major role in governing cell function. Moreover, it is thought that
      gene regulation may be sensitive to nuclear deformations taking place in response
      to extracellular forces over short and long timescales. Although nuclear
      responses to mechanical stimuli over long timescales are relatively well studied,
      the short-term responses are poorly understood. Therefore, to characterize the
      short-term instantaneous deformation of the nucleus in a mechanically dynamic
      environment, we exposed MDCK epithelial monolayers to varying mechanical strain
      fields. The results reveal that nuclei deform anisotropically in response to
      substrate strain, specifically, the minor nuclear axis is significantly more
      deformable than the major axis. We show that upon microtubule depolymerization,
      nuclear deformation anisotropy completely disappears. Moreover, the removal of
      actin causes a significant increase in nuclear deformation along the minor axis
      and a corresponding increase in mechanical anisotropy. The results demonstrate
      that the nucleus deforms in a manner that is very much dependent on the direction
      of strain and the characteristics of the strain field. Actin and microtubules
      also appear to play distinct roles in controlling the anisotropic deformation of
      the nucleus in response to mechanical forces that arise in the cellular
      microenvironment.

PMID- 24123895
TI  - Microstructural design of functionally graded coatings composed of suspension
      plasma sprayed hydroxyapatite and bioactive glass.
AB  - Various bioactive glass/hydroxyapatite (HA) functional coatings were designed by
      the suspension plasma spraying (SPS) technique. Their microstructure, scratch
      resistance, and apatite-forming ability in a simulated body fluid (SBF) were
      compared. The functional coatings design included: (i) composite coating, that
      is, randomly distributed constituent phases; (ii) duplex coating with glass top
      layer onto HA layer; and (iii) graded coating with a gradual changing composition
      starting from pure HA at the interface with the metal substrate up to pure glass
      on the surface. The SPS was a suitable coating technique to produce all the
      coating designs. The SBF tests revealed that the presence of a pure glass layer
      on the working surface significantly improved the reactivity of the duplex and
      graded coatings, but the duplex coating suffered a relatively low scratch
      resistance because of residual stresses. The graded coating therefore provided
      the best compromise between mechanical reliability and apatite-forming ability in
      SBF. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      102B: 551-560, 2014. 

PMID- 24123896
TI  - Commentary: steroid induced diabetes.

PMID- 24123897
TI  - Characterization of intermolecular interaction between cyanidin-3-glucoside and
      bovine serum albumin: spectroscopic and molecular docking methods.
AB  - The intermolecular interaction between cyanidin-3-glucoside (Cy-3-G) and bovine
      serum albumin (BSA) was investigated using fluorescence, circular dichroism and
      molecular docking methods. The experimental results revealed that the
      fluorescence quenching of BSA at 338 nm by Cy-3-G resulted from the formation of
      Cy-3-G-BSA complex. The number of binding sites (n) for Cy-3-G binding on BSA was
      approximately equal to 1. The experimental and molecular docking results revealed
      that after binding Cy-3-G to BSA, Cy-3-G is closer to the Tyr residue than the
      Trp residue, the secondary structure of BSA almost not change, the binding
      process of Cy-3-G with BSA is spontaneous, and Cy-3-G can be inserted into the
      hydrophobic cavity of BSA (site II') in the binding process of Cy-3-G with BSA.
      Moreover, based on the sign and magnitude of the enthalpy and entropy changes
      (DeltaH(0)  = - 29.64 kcal/mol and DeltaS(0)  = - 69.51 cal/mol K) and the
      molecular docking results, it can be suggested that the main interaction forces
      of Cy-3-G with BSA are Van der Waals and hydrogen bonding interactions.

PMID- 24123898
TI  - Investigation of child maltreatment: survey among junior school pupils in Henan
      province of China.
AB  - INTRODUCTION: This study is to examine the prevalence of child maltreatment and
      its association with attachment and self-esteem among junior schools students in
      Henan province of China. METHODS: Seven hundred thirty-six pupils were selected
      from two public schools. Data were collected with the self-reported
      questionnaires of the basic demographic information, the Revised Inventory of
      Parent and Peer Attachment, the Rosenberg Self-Esteem Scale, and the Childhood
      Trauma Questionnaire. Data were analyzed using SPSS 17.0. RESULT: In this study,
      the prevalence of emotional neglect, physical neglect, sexual abuse, emotional
      abuse, and physical abuse were 22.8%, 38.0%, 11.0%, 10.6%, and 7.1%,
      respectively. There was a significant difference between male and female pupils
      in the prevalence of the physical neglect (Pearson chi(2)  = 16.27, P < 0.01),
      sexual abuse (chi(2)  = 15.38, P < 0.01), and physical abuse (chi(2)  = 11.55, P
      < 0.01). In addition, physical neglect was the most common reported by pupils in
      the child maltreatment. Drinking habit of the mother was a significantly risk
      factor for emotional abuse, emotional neglect, and physical neglect. CONCLUSION:
      Child abuse is still a severe social and psychological problem, and child neglect
      is more common than child abuse. It is noteworthy that mothers with drinking
      habit were more likely to abuse their own children than fathers with drinking
      habit.

PMID- 24123899
TI  - Prospective evaluation for respiratory pathogens in children with sickle cell
      disease and acute respiratory illness.
AB  - BACKGROUND: Human rhinovirus (HRV), human coronavirus (hCoV), human bocavirus
      (hBoV), and human metapneumovirus (hMPV) infections in children with sickle cell
      disease have not been well studied. PROCEDURE: Nasopharyngeal wash specimens were
      prospectively collected from 60 children with sickle cell disease and acute
      respiratory illness, over a 1-year period. Samples were tested with multiplexed
      PCR, using an automated system for nine respiratory viruses, Chlamydophila
      pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Clinical
      characteristics and distribution of respiratory viruses in patients with and
      without acute chest syndrome (ACS) were evaluated. RESULTS: A respiratory virus
      was detected in 47 (78%) patients. Nine (15%) patients had ACS; a respiratory
      virus was detected in all of them. The demographic characteristics of patients
      with and without ACS were similar. HRV was the most common virus, detected in 29
      of 47 (62%) patients. Logistic regression showed no association between ACS and
      detection of HRV, hCoV, hBoV, hMPV, and other respiratory pathogens. Co-infection
      with at least one additional respiratory virus was seen in 14 (30%) infected
      patients, and was not significantly higher in patients with ACS (P = 0.10). Co
      infections with more than two respiratory viruses were seen in seven patients,
      all in patients without ACS. Bacterial pathogens were not detected. CONCLUSION:
      HRV was the most common virus detected in children with sickle cell disease and
      acute respiratory illness, and was not associated with increased morbidity.
      Larger prospective studies with asymptomatic controls are needed to study the
      association of these emerging respiratory viruses with ACS in children with
      sickle cell disease.

PMID- 24123900
TI  - Fine-scale population genetics analysis of Platynereis dumerilii (Polychaeta,
      Nereididae) in the Black Sea: how do local marine currents drive geographical
      differentiation?
AB  - In this study we analyzed at a submeso-geographic scale (2 km) the genetic
      diversity of two sub-populations of Platynereis dumerilii and correlated this
      with the physical characteristics of the marine currents along the western Black
      Sea coast. For this purpose, we developed a set of 13 new polymorphic
      microsatellite markers and used them to assess the genetic differentiation, as
      well as the bi-directional migration rates between the studied sub-populations.
      We also computed the Peclet number (Pe) as an indicator of the relative effect of
      advection and eddy diffusion on larval dispersion for the specific conditions of
      the Black Sea study area. The results indicated no genetic structure in P.
      dumerilii sub-populations which indicates that the longitudinal alongshore
      currents dominate in the population structuring of this species. This finding is
      important, because with the average current speeds of 5 cm/sec on the Black Sea
      coast during May-August we might have expected a certain population structuring
      to occur. In accordance with the periodical change of direction of the
      longitudinal current (either form North to South, or form South to North) the
      gene flow was found to be bi-directional, with the same intensity.

PMID- 24123901
TI  - Relationship between ganglion cell-inner plexiform layer and optic disc/retinal
      nerve fibre layer parameters in non-glaucomatous eyes.
AB  - AIMS: To determine the relationship between macular ganglion cell-inner plexiform
      layer (GC-IPL) thickness and optic disc/retinal nerve fibre layer (RNFL)
      parameters in non-glaucomatous eyes measured by spectral-domain optical coherence
      tomography (SD-OCT). METHODS: 491 non-glaucomatous Chinese aged 40-80 years were
      recruited from a population-based study and underwent standardised ophthalmic
      examination. SD-OCT was used to measure GC-IPL thickness, optic disc parameters
      and RNFL thickness. Univariate and multiple linear regression analyses were
      performed to assess the association between GC-IPL and optic disc/RNFL
      parameters. RESULTS: In univariate analyses, all RNFL parameters and rim area
      were significantly correlated with all macular GC-IPL parameters (p<0.001, r=0.12
      0.56). In multiple regression analyses, after adjusting for age, gender, disc
      area, signal strength and axial length, average RNFL thickness (per um decrease)
      was most strongly correlated with average GC-IPL thickness (beta=-0.30,
      standardised beta=-0.499, p<0.001) compared with other optic disc/RNFL
      parameters. CONCLUSIONS: Our study demonstrated only fair correlations between
      macular GC-IPL and optic disc/RNFL parameters measured by SD-OCT. This
      information is important for further evaluation of macular GC-IPL thickness as an
      additional marker in detecting glaucomatous damage and progression.

PMID- 24123902
TI  - All biometric components are important in anisometropia, not just axial length.
AB  - BACKGROUND: No study to date has looked into the relationship between ocular
      biometrics with anisometropia exclusively; therefore, the purpose of this study
      was to determine the relationship between anisometropia and ocular biometrics.
      METHODS: In a cross-sectional study with multistage cluster sampling, 6311 people
      in the 40-64-year-old age group from the population of Shahroud, Iran, were
      selected. Of these, 5190 people participated in the study. For all participants,
      tests for visual acuity, cycloplegic and non-cycloplegic refraction, slit lamp
      test and fundoscopy were performed. All participants underwent biometric
      examinations using the Allegro Biograph (WaveLight AG, Erlangen, Germany).
      RESULTS: Asymmetry of axial length, corneal power, vitreous chamber depth,
      anterior chamber depth, lens thickness and lens power were significantly more
      among participants who were anisometropic than those who were non-anisometropic.
      The correlation of anisometropia with axial length asymmetry was 0.735, 0.273
      with corneal power, 0.183 with anterior chamber depth and 0.311 with lens power
      (p<0.001). In a multiple linear regression model, anisometropia was found to have
      significant associations with axial length asymmetry (standard coefficient
      (SC)=0.905), corneal power asymmetry (SC=0.350), lens power asymmetry (SC=0.454),
      nuclear opacity asymmetry (SC=0.074) and age (SC=0.28) (R(2)=85.1%). According to
      the linear regression model, corneal power had the strongest association with
      anisoastigmatism. CONCLUSIONS: Axial length asymmetry has the strongest
      correlation with anisometropia; nonetheless, other components of ocular
      biometrics such as corneal power, lens opacity, lens power and anterior chamber
      depth are related to anisometropia as well. More than 10% of changes in
      anisometropia can be explained with changes in factors other than asymmetry of
      ocular biometrics and lens opacity.

PMID- 24123903
TI  - Clinical evaluation of a multifocal aspheric diffractive intraocular lens.
AB  - AIM: To evaluate the performance of an aspheric diffractive multifocal acrylic
      intraocular lens (IOL), ZMB00 1-Piece Tecnis. SETTING: Five sites across Europe.
      METHODS: Fifty-two patients with cataracts (average age 68.5+/-10.5 years, 35
      female) were bilaterally implanted with the aspheric diffractive multifocal IOL
      after completing a questionnaire regarding their optical visual symptoms, use of
      visual correction and their visual satisfaction. The questionnaire was completed
      again 4-6 months after surgery along with measures of uncorrected and best
      corrected distance and near visual acuity, under photopic and mesopic lighting,
      reading ability, defocus curve testing and ocular examination for adverse events.
      RESULTS: The residual refractive error was 0.01+/-0.47D with 56% of eyes within
      +/-0.25D and 97% within +/-1.0D. Uncorrected visual acuity was 0.02+/-0.10logMAR
      at distance and 0.15+/-0.30 logMAR at near, only reducing to 0.07+/-0.10logMAR at
      distance and 0.21+/-0.25logMAR at near in mesopic conditions.The defocus curve
      showed a near addition between 2.5-3.0 D allowing a reading acuity of 0.08+/-0.13
      logMAR, with a range of clear vision <0.3 logMAR of ~4.0 D. The average reading
      speed was 121.4+/-30.8 words per minute. Spectacle independence was 100% for
      distance and 88% for near, with high levels of satisfaction reported. Overall
      rating of vision without glasses could be explained (r=0.760) by preoperative
      best-corrected distance acuity, postoperative reading acuity and postoperative
      uncorrected distance acuity in photopic conditions (p<0.001). Only two minor
      adverse events occurred. CONCLUSIONS: The ZMB00 1-Piece Tecnis multifocal IOL
      provides a good visual outcome at distance and near with minimal adverse effects.

PMID- 24123904
TI  - Impact of dry eye on reading in a population-based sample of the elderly: the
      Salisbury Eye Evaluation.
AB  - BACKGROUND/AIMS: People with dry eye often complain of difficulty reading, but
      this perceived deficit has not been appropriately quantified. The purpose of this
      study is to determine if dry eye is associated with measurable reading deficits.
      METHODS: A cross-sectional study of 1981 participants in the Salisbury Eye
      Evaluation, a population-based study of the elderly. Dry eye symptoms were
      identified by questionnaire and clinically significant dry eye was defined as the
      presence of dry eye symptoms and positive Schirmer testing or ocular surface
      staining in either eye. Spoken reading speed was measured using short text
      passages. Subjects self-reported if they did not read or had difficulty reading
      newsprint. RESULTS: 13.8% of subjects (274/1981) had dry eye symptoms and 3.1%
      (62/1981) had clinically significant dry eye. There was no difference in reading
      speed between subjects with dry eye symptoms or clinically significant dry eye
      and their controls (p=0.99 and 0.78, respectively) in multivariable models.
      Compared with asymptomatic subjects, however, subjects with dry eye symptoms were
      more likely to report reading difficulty (OR=1.7, 95% CI 1.3 to 2.4, p<0.01) and
      not reading newsprint (OR=1.9, 95% CI 1.0 to 3.6, p=0.04). Similarly, subjects
      with clinically significant dry eye were more likely to report difficulty reading
      newsprint (OR=2.5, 95% CI 1.4 to 4.5, p<0.01) or not reading newsprint at all
      (OR=4.1, 95% CI 1.6 to 10.7, p<0.01) as compared with subjects without dry eye
      signs or symptoms. CONCLUSIONS: Dry eye did not significantly affect reading
      speed but was associated with self-reported reading difficulty and avoidance of
      newspaper reading in this elderly population-based sample.

PMID- 24123905
TI  - Mortality and hospital morbidity of working-age blind.
AB  - AIM: Determine whether blindness in people aged 18-65 years was associated with
      increased rates of mortality, hospitalisation and length of stay. METHODS: A
      retrospective matched cohort study of legally blind people and normally sighted
      controls, aged 18-65 years, comparing mortality rates and hospital morbidity
      records. RESULTS: Together, 419 blind and 419 controls accumulated 12 258
      hospital separations over the 11-year study period. The blind had an age-specific
      mortality rate seven times greater (12/1000 person years) than the general
      population (1.8/1000 person years) (p<0.001). Blindness was recorded as a
      comorbid condition for 76 (22%) blind individuals, on just 255 (2.3%) hospital
      separation records. Psychiatric, mental or behavioural conditions were the most
      frequently recorded diagnoses, after dialysis and endocrine conditions. After
      adjusting for comorbidities, the blind cohort had 1.5 times more hospital
      separations (p=0.007, 95% CI 1.1 to 2.0) and 2.2 times more bed days (p=0.016,
      95% CI 1.4 to 4.1) compared with the control cohort. CONCLUSIONS: Recognition and
      acknowledgement of in-patients' blind status may assist in understanding the
      frequent and extended health service utilisation rates. Encouraging and promoting
      the uptake and access to rehabilitation support services would be measures that
      may reduce the health service burden of blindness, the incidence of depression
      and other mental health problems.

PMID- 24123906
TI  - New insights into the visual prognosis of pseudoxanthoma elasticum.

PMID- 24123907
TI  - Retinal thickness and visual acuity in highly myopic eyes.

PMID- 24123908
TI  - Vascular endothelial growth factor gene polymorphism and protein expression in
      the pathogenesis of pterygium.
AB  - BACKGROUND AND AIMS: Vascular endothelial growth factor (VEGF) gene expression
      has been linked to cancer progression. Here we hypothesise that the polymorphism
      and protein expression of VEGF are correlated with the pathogenesis and therapy
      response of pterygium. METHODS: 60 pterygial and 121 normal conjunctival samples
      were collected to determine the genotypes and protein expression of VEGF. Primary
      pterygium cells (PECs) were used to confirm the effect of the VEGF polymorphism
      on the angiogenesis of pterygium. RESULTS: 48 (83.3%) pterygial specimens tested
      positive for VEGF protein expression, which was significantly higher than in the
      control groups (16.7%, p<0.0001). The frequency of the 936 C>T variant, but not
      the -2578C>A variant, was significantly higher in the pterygium group compared
      with the control group. VEGF protein expression was significantly higher in the
      936 C/C group than in the 936 C/T and T/T groups (p=0.001). The results of our
      cell model showed that PECs with the C/C genotype had a higher angiogenesis
      ability and higher response to the antiangiogenesis drug bevacizumab than cells
      with the C/T and T/T genotypes. CONCLUSIONS: We suggest that VEGF could be used
      as a target for pterygium therapy in patients with the 936C>T genotype.

PMID- 24123909
TI  - Development of a quality improvement program in a department of ophthalmology.
AB  - OBJECTIVE: To design and implement a quality improvement (QI) programme in an
      academic department of ophthalmology. DESIGN: The six core competencies of the
      Accreditation Council for Graduate Medical Education serve as the model for this
      programme in an institutional practice. The authors review departmental rates of
      postoperative infections, unplanned reoperations, intraoperative complications,
      specific subspecialty postoperative complications and successes, and patient and
      staff compliments and complaints. RESULTS: The authors describe the structure and
      evolution of the QI programme in our ophthalmology department. CONCLUSIONS: It is
      possible to implement a structured QI programme in an academic department of
      ophthalmology. With healthcare oversight increasing, physician self-monitoring of
      quality of care measures will become even more important.

PMID- 24123910
TI  - Periocular basal cell carcinoma pathological reporting.

PMID- 24123911
TI  - Technique of endoscopic ultrasonography-guided pancreatic duct intervention (with
      videos).
AB  - To date, several endoscopic ultrasonography (EUS)-guided interventions have been
      reported. Of these interventions, EUS-guided pancreatic duct (PD) intervention
      seems to be the most difficult and challenging procedure to accomplish. We
      provide suggestions for EUS-guided PD intervention, which includes PD stenting
      and the rendezvous technique following EUS-guided pancreatography. PD stenting is
      performed between the PD and the gastrointestinal tract (stomach, duodenum, or
      jejunum). The rendezvous technique is performed using a guidewire across the
      papilla or anastomotic site for retrograde stent insertion. EUS-guided PD
      intervention is still challenging because it is not established yet. Thus,
      although EUS-guided PD intervention seems to be promising, it should be performed
      in selected patients such as those of failed standard endoscopic retrograde
      cholangiopancreatography. 

PMID- 24123912
TI  - First isomers of pristine C104 fullerene structurally confirmed as chlorides,
      C104(258)Cl16 and C104(812)Cl24.
AB  - Isolation and characterization of very large fullerenes is hampered by a drastic
      decrease of their content in fullerene soot with increasing fullerene size and a
      simultaneous increase of the number of possible IPR (Isolated Pentagon Rule)
      isomers. In the present work, fractions containing mixtures of C102 and C104 were
      isolated in very small quantities (several dozens of micrograms) by multi-step
      recycling HPLC from an arc-discharge fullerene soot. Two such fractions were used
      for chlorination with a VCl4/SbCl5 mixture in glass ampoules at 350-360  degrees
      C. The resulting chlorides were investigated by single-crystal X-ray diffraction
      using synchrotron radiation. By this means, two IPR isomers of C104 , numbers 258
      and 812 (of 823 topologically possible isomers), have been confirmed for the
      first time as chlorides, C1 -C104(258)Cl16 and D2-C104 (812)Cl24, respectively,
      while an admixture of C2 -C104(811)Cl24 was assumed to be present in the latter
      chloride. DFT calculations showed that pristine C104(812) belongs to rather
      stable C104 cages, whereas C104(258) is much less stable.

PMID- 24123914
TI  - N-trifluoromethylthiophthalimide: a stable electrophilic SCF3 -reagent and its
      application in the catalytic asymmetric trifluoromethylsulfenylation.
AB  - Cinchona alkaloid catalysts in combination with air- and moisture-stable N
      trifluoromethylthiophthalimide as electrophilic SCF3 source enabled the catalytic
      enantioselective trifluoromethylsulfenylation. Thus, a series of alpha-SCF3
      esters that bear a quaternary carbon stereogenic center were obtained with
      excellent yield and enantioselectivity. Moreover, the products can be readily
      converted into valuable alpha-SCF3 beta-hydroxyesters. 

PMID- 24123915
TI  - Dendritic differentiation of cerebellar Purkinje cells is promoted by ryanodine
      receptors expressed by Purkinje and granule cells.
AB  - Cerebellar Purkinje cells have the most elaborate dendritic trees among neurons
      in the brain. We examined the roles of ryanodine receptor (RyR), an intracellular
      Ca(2+) release channel, in the dendrite formation of Purkinje cells using
      cerebellar cell cultures. In the cerebellum, Purkinje cells express RyR1 and
      RyR2, whereas granule cells express RyR2. When ryanodine (10 uM), a blocker of
      RyR, was added to the culture medium, the elongation and branching of Purkinje
      cell dendrites were markedly inhibited. When we transferred small interfering RNA
      (siRNA) against RyR1 into Purkinje cells using single-cell electroporation,
      dendritic branching but not elongation of the electroporated Purkinje cells was
      inhibited. On the other hand, transfection of RyR2 siRNA into granule cells also
      inhibited dendritic branching of Purkinje cells. Furthermore, ryanodine reduced
      the levels of brain-derived neurotrophic factor (BDNF) in the culture medium. The
      ryanodine-induced inhibition of dendritic differentiation was partially rescued
      when BDNF was exogenously added to the culture medium in addition to ryanodine.
      Overall, these results suggest that RyRs expressed by both Purkinje and granule
      cells play important roles in promoting the dendritic differentiation of Purkinje
      cells and that RyR2 expressed by granule cells is involved in the secretion of
      BDNF from granule cells.

PMID- 24123913
TI  - Undifferentiated human adipose-derived stromal/stem cells loaded onto wet-spun
      starch-polycaprolactone scaffolds enhance bone regeneration: nude mice calvarial
      defect in vivo study.
AB  - The repair of large bony defects remains challenging in the clinical setting.
      Human adipose-derived stromal/stem cells (hASCs) have been reported to
      differentiate along different cell lineages, including the osteogenic. The
      objective of the present study was to assess the bone regeneration potential of
      undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a
      critical-sized nude mice calvarial defect. Human ASCs were isolated from
      lipoaspirate of five female donors, cryopreserved, and pooled together. Critical
      sized (4 mm) calvarial defects were created in the parietal bone of adult male
      nude mice. Defects were either left empty, treated with an SPCL scaffold alone,
      or SPCL scaffold with human ASCs. Histological analysis and Micro-CT imaging of
      the retrieved implants were performed. Improved new bone deposition and
      osseointegration was observed in SPCL loaded with hASC engrafted calvarial
      defects as compared to control groups that showed little healing.
      Nondifferentiated human ASCs enhance ossification of nonhealing nude mice
      calvarial defects, and wet-spun SPCL confirmed its suitability for bone tissue
      engineering. This study supports the potential translation for ASC use in the
      treatment of human skeletal defects.

PMID- 24123916
TI  - The effect of human chorionic gonadotropin-based hormonal therapy on
      intratesticular testosterone levels and spermatogonial DNA synthesis in men with
      non-obstructive azoospermia.
AB  - The use of hormonal therapy in men with non-obstructive azoospermia (NOA) is
      controversial because no information is available on how it affects
      intratesticular testosterone (ITT) levels and spermatogenic cells. The aim of
      this study was to investigate the ITT level and spermatogonial DNA synthesis, as
      determined by proliferating cell nuclear antigen (PCNA) expression, before and
      after human chorionic gonadotropin (hCG)-based hormonal therapy in men with NOA.
      Twenty patients who failed sperm retrieval procedures using microdissection
      testicular sperm extraction (micro-TESE) were enrolled in hCG-based hormonal
      therapy prior to a second micro-TESE. The patients' ITT levels were determined
      from testicular fluid obtained during the micro-TESE. Spermatogonial PCNA
      expression was determined by immunohistochemical analysis, and the PCNA labelling
      index (PCNA-LI) was calculated. During the second micro-TESE, spermatozoa were
      successfully retrieved from three (15%) of the men who had been treated with
      hormonal therapy. PCNA-positive cells were predominantly in the spermatogonia and
      primary spermatocytes, and PCNA-LI was significantly increased after the hormonal
      therapy. A significant increase in the ITT levels before and after the hormonal
      therapy (p < 0.0001, 273.6 +/- 134.4 and 1348.1 +/- 505.4 ng/mL respectively).
      The sperm-positive group showed a significantly lower basal ITT level compared
      with the sperm-negative group (p < 0.05). There was a marked increase in the PCNA
      LI levels of men treated with both recombinant human follicle-stimulating hormone
      and hCG. In addition, there was a significant negative association between the
      increase in PCNA-LI and basal ITT levels at the initial micro-TESE (p < 0.05),
      but not the stimulated ITT level at the second micro-TESE. HCG-based hormonal
      therapy significantly raises the ITT level and stimulates spermatogonial DNA
      synthesis, potentially improving spermatogenesis. ITT optimization plays, at
      least in part, an important role for stimulating spermatogenesis in men with NOA.

PMID- 24123917
TI  - Early childhood wheezing is associated with lower lung function in cystic
      fibrosis.
AB  - OBJECTIVE: To study the association between wheezing in children with cystic
      fibrosis (CF) and lung function in later life. METHODS: We used data from the
      Epidemiologic Study of CF, a longitudinal observational study from 1994 to 2005.
      Wheezing phenotypes were defined as: no wheezing in the first 6 years of life
      (NW), transient wheezing (TW; wheezing <3 years old, but no wheezing after 3),
      late wheezing (LW; wheezing only after age 3 years), and persistent wheezing (PW;
      wheezing both before and after age 3 years). A linear regression model was
      developed predicting the best forced expiratory volume in 1 sec (FEV1 ) at age 6
      or 7 years (6 to <8) for each wheezing phenotype. RESULTS: A total of 1302
      children met the cohort inclusion criteria; 61% of the cohort had wheezing in the
      first 6 years of life. A history of any wheezing in the first 6 years of life was
      associated with a significantly lower FEV1 at 6 to <8 years compared to children
      with NW. The FEV1 of children with NW at age 6 to <8 years was 104% predicted,
      whereas the mean FEV1 in TW, LW, and PW groups was 98%, 100%, and 96% predicted,
      respectively (P < 0.05 compared to NW). CONCLUSIONS: Childhood wheezing in CF is
      common and is associated with lower lung function at age 6 to <8 years. Our
      results identify a clinical feature in early childhood CF associated with lower
      lung function in later life.

PMID- 24123918
TI  - The influence of polymeric component of bioactive glass-based nanocomposite paste
      on its rheological behaviors and in vitro responses: hyaluronic acid versus
      sodium alginate.
AB  - Different biocomposite pastes were prepared from a solid phase that was
      nanoparticles of sol-gel-derived bioactive glass and different liquid phases
      including 3% hyaluronic acid solution, sodium alginate solutions (3% and 10 %) or
      mixtures of hyaluronic acid and sodium alginate (3% or 10 %) solutions in 50:50
      volume ratio. Rheological properties of the pastes were measured in both rotatory
      and oscillatory modes. The washout behavior and in vitro apatite formation of the
      pastes were determined by soaking them in simulated body fluid under dynamic
      situation for 14 days. The proliferation and alkaline phosphatase activity of MG
      63 osteoblastic cells were also determined using extracts of the pastes. All
      pastes could be easily injected from the standard syringes with different tip
      diameters. All pastes exhibited visco-elastic character, but a nonthixotropic
      paste was obtained using hyaluronic acid in which the loss modulus was higher
      than the storage modulus. The thixotropy and storage modulus were increasingly
      improved by adding/using sodium alginate as mixing liquid. Moreover, the pastes
      in which the liquid phase was sodium alginate or mixture of hyaluronic acid and
      10% sodium alginate solution revealed better apatite formation ability and
      washout resistance than that made of hyaluronic acid alone. No cytotoxicity
      effects were observed by extracts of the pastes on osteoblasts but better
      alkaline phosphatase activity was found for the pastes containing hyaluronic
      acid. Overall, injectable biocomposites can be produced by mixing bioactive glass
      nanoparticles and sodium alginate/hyaluronic acid polymers. They are potentially
      useful for hard and even soft tissues treatments.

PMID- 24123919
TI  - Biomimetic materials design for cardiac tissue regeneration.
AB  - Cardiovascular disease is the leading cause of death worldwide. In the absence of
      sufficient numbers of organs for heart transplant, alternate approaches for
      healing or replacing diseased heart tissue are under investigation. Designing
      biomimetic materials to support these approaches will be essential to their
      overall success. Strategies for cardiac tissue engineering include injection of
      cells, implantation of three-dimensional tissue constructs or patches, injection
      of acellular materials, and replacement of valves. To replicate physiological
      function and facilitate engraftment into native tissue, materials used in these
      approaches should have properties that mimic those of the natural cardiac
      environment. Multiple aspects of the cardiac microenvironment have been emulated
      using biomimetic materials including delivery of bioactive factors, presentation
      of cell-specific adhesion sites, design of surface topography to guide tissue
      alignment and dictate cell shape, modulation of mechanical stiffness and
      electrical conductivity, and fabrication of three-dimensional structures to guide
      tissue formation and function. Biomaterials can be engineered to assist in stem
      cell expansion and differentiation, to protect cells during injection and
      facilitate their retention and survival in vivo, and to provide mechanical
      support and guidance for engineered tissue formation. Numerous studies have
      investigated the use of biomimetic materials for cardiac regeneration. Biomimetic
      material design will continue to exploit advances in nanotechnology to better
      recreate the cellular environment and advance cardiac regeneration. Overall,
      biomimetic materials are moving the field of cardiac regenerative medicine
      forward and promise to deliver new therapies in combating heart disease.

PMID- 24123920
TI  - Activation of dinitrogen-derived hafnium nitrides for nucleophilic N-C bond
      formation with a terminal isocyanate.
AB  - Better by Hf: Anion coordination to a bridging hafnocene nitride complex,
      prepared from CO-induced N2 cleavage, increases the nucleophilicity of the
      nitrogen atom, thus promoting additional N?C bond formation with a typically
      inert terminal isocyanate ligand. This cascade sequence allows synthesis of
      otherwise challenging mono-substituted ureas using N2 , CO, and an appropriate
      electrophile. 

PMID- 24123921
TI  - Effects of neuregulin-1 genetic variation and depression symptom severity on
      longitudinal patterns of psychotic symptoms in primary care attendees.
AB  - A better understanding of the factors associated with psychotic symptoms could
      aid early identification and treatment of psychotic disorders. Previous studies
      have typically utilized cross-sectional study designs and have focused on
      individuals with psychotic disorders. Thus, examination of promising correlates
      of psychotic symptoms using longitudinal designs among more broadly defined
      populations is warranted. Two such correlates are neuregulin-1 (NRG1) genotypic
      variation and depression symptom severity. Both NRG1 and depression symptom
      severity have cross-sectional evidence for an association with psychosis but
      their affect on longitudinal patterns of psychotic symptoms and their potential
      interaction effects are less clear. Using repeated measures analysis of variance
      and covariance we modeled the main and interaction effects of NRG1 genotypic
      variation and depressive symptom severity on longitudinal psychotic symptom
      patterns in 301 primary care attendees assessed annually over 4 years. One-fifth
      (19.9%) of the participants reported one or more psychotic symptoms over the 4
      year assessment period. We observed a curvilinear (i.e., cubic) association
      between depression symptom severity at baseline and longitudinal patterns of
      psychotic symptoms but did not observe a main effect for NRG1 genotypic variation
      on psychotic symptom patterns. However, NRG1 rs6994992 genotype moderated the
      curvilinear association between depression symptom severity and psychotic symptom
      patterns. Specifically, depression symptom severity had less of an effect on
      longitudinal psychotic symptoms among carriers of the rs6994992 TT genotype
      compared to CC and CT carriers. Our findings suggest a curvilinear association
      between depression symptom severity and longitudinal patterns of psychotic
      symptoms that is moderated by NRG1 genotype.

PMID- 24123922
TI  - MED12 related disorders.
AB  - MED12: is a member of the large Mediator complex, which has a critical and
      central role in RNA polymerase II transcription. As a multiprotien complex,
      Mediator regulates signals involved in cell growth, development, and
      differentiation, and it is involved in a protein network required for
      extraneuronal gene silencing and also functions as a direct suppressor of Gli3
      dependent Sonic hedgehog signaling. This may explain its role in several
      different X-linked intellectual disability syndromes that share some overlapping
      clinical features. This review will compare and contrast four different clinical
      conditions that have been associated with different mutations in MED12, which is
      located at Xq13. To date, these conditions include Opitz-Kaveggia (FG) syndrome,
      Lujan syndrome, Ohdo syndrome (Maat-Kievit-Brunner type, or OSMKB), and one large
      family with profound X-linked intellectual disability due to a novel c.5898insC
      frameshift mutation that unlike the other three syndromes, resulted in affected
      female carriers and truncation of the MED12 protein. It is likely that more MED12
      mutations will be detected in sporadic patients and X-linked families with
      intellectual disability and dysmorphic features as exome sequencing becomes more
      commonly utilized, and this overview of MED12-related disorders may help to
      correlate MED12 genotypes with clinical findings.

PMID- 24123923
TI  - A novel approach to achieving modular retrovirus clearance for a parvovirus
      filter.
AB  - Viral filtration is routinely incorporated into the downstream purification
      processes for the production of biologics produced in mammalian cell cultures
      (MCC) to remove potential viral contaminants. In recent years, the use of
      retentive filters designed for retaining parvovirus (~20 nm) has become an
      industry standard in a conscious effort to further improve product safety. Since
      retentive filters remove viruses primarily by the size exclusion mechanism, it is
      expected that filters designed for parvovirus removal can effectively clear
      larger viruses such as retroviruses (~100 nm). In an attempt to reduce the number
      of viral clearance studies, we have taken a novel approach to demonstrate the
      feasibility of claiming modular retrovirus clearance for Asahi Planova 20N
      filters. Porcine parvovirus (PPV) and xenotropic murine leukemia virus (XMuLV)
      were co-spiked into six different feedstreams and then subjected to laboratory
      scale Planova 20N filtration. Our results indicate that Planova 20N filters
      consistently retain retroviruses and no retrovirus has ever been detected in the
      filtrates even when significant PPV breakthrough is observed. Based on the data
      from multiple in-house viral validation studies and the results from the co
      spiking experiments, we have successfully claimed a modular retrovirus clearance
      of greater than 6 log10 reduction factors (LRF) to support clinical trial
      applications in both USA and Europe.

PMID- 24123924
TI  - Atmospheric chemistry and environmental assessment of inhalational fluroxene.
AB  - Smog chamber/gas chromatography techniques are used to investigate the
      atmospheric degradation of fluroxene, an anesthetic, through oxidation with OH
      and Cl radicals at 298 K and under atmospheric pressure of N2 or air. The
      measured rate constants (k) are: k(fluroxene+OH(.) )=(2.96+/-0.61)*10(-11) and
      k(fluroxene+Cl(.) )=(1.62+/-0.19)*10(-10) cm(3)  molecule(-1)  s(-1) . The only
      product detected after the oxidation of fluroxene with OH radicals is 2,2,2
      trifluoroethyl formate (79 % and 83 % molar yield in the absence and presence of
      NOx, respectively). However, after oxidation with Cl radicals, the detected
      products are 2,2,2-trifluoroethyl formate (78 %), 2,2,2-trifluoroethyl-1
      chloroacetate (5 %), and chloroacetaldehyde (4 %), in the absence of NOx, and
      2,2,2-trifluoroethyl formate (93 %), 2,2,2-trifluoroethyl-1-chloroacetate (6 %),
      and chloroacetaldehyde (5 %), in the presence of NOx. The results indicate that,
      both in the absence and presence of NOx, the main fate of fluroxene is the
      addition of the oxidant to the double bond and, once the alkoxy radical is
      formed, the main decomposition pathway is by means of degradation. Moreover, it
      is expected that 2,2,2-trifluoroethyl formate is the only oxidation product able
      to actively contribute to climate change. To successfully assess the contribution
      of fluroxene to global warming, we measure the infrared spectra of fluroxene and
      2,2,2-trifluoroethyl formate, and calculate the radiative efficiencies (REs) to
      be 0.27 and 0.28 W m(-2)  ppbv(-1) , respectively. In addition, the cumulative
      effect owing to the formation of 2,2,2-trifluoroethyl formate is investigated,
      and the direct, indirect, and net global-warming potentials are calculated by
      using the REs and lifetimes of fluroxene and 2,2,2-trifluoroethyl formate. 

PMID- 24123926
TI  - Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute
      kidney injury in patients treated with goal-directed haemodynamic therapy after
      major abdominal surgery.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a
      new biomarker for the early identification of acute kidney injury (AKI). There is
      also increasing evidence of an association between urinary albumin/creatinine
      ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical
      utility of these biomarkers to predict AKI in a population of perioperative
      patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims
      were to examine NGAL and ACR as sensitive biomarkers to detect the effects of
      GDHT and to investigate the association of these biomarkers with secondary
      outcomes. METHODS: Urine was obtained from 109 patients admitted to a critical
      care unit following major abdominal surgery. Patients were treated with
      intravenous fluid, GDHT with intravenous fluid or GDHT with intravenous fluid and
      dopexamine. Urine was collected preoperatively, and at times 0, 8 and 24 h
      postoperatively and outcome monitored for 28 days. RESULTS: There were no
      significant differences in NGAL or ACR concentrations between the cohorts treated
      with GDHT compared to standard care. However, both biomarker concentrations rose
      significantly in all cohorts over the time points. There were no significant
      differences in NGAL observed between patients who developed AKI and those who did
      not. However, there were significantly higher ACR preoperatively in patients who
      developed AKI. There were higher NGAL concentrations in patients who developed an
      infection and who died. CONCLUSIONS: NGAL has a poor predictive role in
      evaluating AKI in this clinical setting. Preoperative ACR may have a role as an
      AKI marker.

PMID- 24123927
TI  - Separation and purification of antioxidants from Ampelopsis heterophylla by
      counter-current chromatography.
AB  - In this study, bioactive components from Ampelopsis heterophylla were separated
      by counter-current chromatography (CCC). The antioxidant activity of the crude
      extract was initially evaluated by an online HPLC method. Five compounds in the
      crude extract exhibited good antioxidant activities, namely, hyperoside (1),
      isoquercitrin (2), rutin (3), kaempferol-3-rutinoside (4), and quercetin (5).
      These compounds were further separated by CCC with biphasic solvent systems and
      their structures were identified by MS and NMR spectroscopy. All the compounds
      exhibited significant 1,1-diphenyl-2-picryl-hydrazyl radical scavenging
      activities with IC50 values at 18.2 +/- 1.3, 17.0 +/- 1.4, 24.2 +/- 1.2, 38.1 +/-
      1.7, and 9.0 +/- 1.2 MUM, respectively. The scavenging ratios of the compounds
      against hydroxyl radicals were 65 +/- 5, 68 +/- 4, 96 +/- 2, 70 +/- 4, and 98 +/-
      2%, respectively.

PMID- 24123928
TI  - Hepatitis E infection in liver transplant recipients.
AB  - Hepatitis E virus (HEV) infection (genotype 3) has been described in developed
      countries as a cause of chronic hepatitis in recipients of solid organ
      transplantation (SOT), with the first cases reported in 2008. Immunosuppression
      seems to play a major role in the pathogenesis of chronic infections. The current
      gold standard for the diagnosis of HEV infection is the detection of HEV RNA in
      serum, stools, or both. In liver transplant recipients, HEV infection is
      considered an uncommon disease; however, a high index of suspicion is needed for
      patients with graft hepatitis of an unclear etiology. Liver transplant recipients
      seem more likely to develop chronic HEV after an acute infection, and there is
      accelerated progression to advanced fibrosis and cirrhosis. A decrease in
      immunosuppression is considered the first line of treatment, and pegylated
      interferon can be considered the second line of treatment for liver transplant
      recipients. At the present time, there are not enough data to recommend treatment
      with ribavirin for adult liver transplant recipients, although this has been
      tried in other SOT populations.

PMID- 24123929
TI  - Derivation of aortic distensibility and pulse wave velocity by image registration
      with a physics-based regularisation term.
AB  - Analysis of the cardiovascular system represents a classical problem in which the
      solid and fluid phases interact intimately, and so is a rich field of application
      for state-of-the-art fluid-solid interaction (FSI) analyses. In this paper, we
      focus on the human aorta. Solution of the full FSI problem requires knowledge of
      the material properties of the wall and information on vessel support. We show
      that variation of distensibility along the aorta can be obtained from four
      dimensional image data using image registration. If pressure data at one point in
      the vessel are available, these can be converted to absolute values.
      Alternatively, values of pulse wave velocity along the vessel can be obtained.
      The quality of the extracted data is improved by the incorporation into the
      registration of a regularisation term based on the one-dimensional wave equation.
      The method has been validated using simulated data. For idealised vessels, the
      accuracy with which the distensibility and wave velocity can be extracted is high
      (1%-2%). The method is applied to six clinical datasets from patients with mild
      coarctation, for which it is shown that wave velocity along the aorta is
      relatively constant.

PMID- 24123931
TI  - Improvement of lateral resolution and extension of depth of field in two-photon
      microscopy by a higher-order radially polarized beam.
AB  - The spatial resolution of laser scanning microscopes depends on the focal spot
      size. As previously reported, we successfully improved the lateral spatial
      resolution in confocal microscopy using liquid crystal devices (LCDs) to convert
      a linearly polarized (LP) beam into a higher-order radially polarized (HRP) beam.
      Taking advantage of the fact that those LCDs can be utilized at various
      wavelengths, including near-infrared, we employed a near-infrared HRP beam to
      improve the resolution in two-photon microscopy. Point-spread functions estimated
      from fluorescent beads embedded in agarose gel showed that an HRP beam at 800-nm
      excitation improved lateral resolution to 230 nm from 294 nm, which was obtained
      using an LP beam at the same wavelength. Furthermore, at the glass-water
      interface, the lateral resolution was considerably improved to 188 nm using the
      HRP beam, whereas it degraded to 510 nm while using the LP beam. The HRP beams
      visualized fine intracellular structures not only in fixed cells stained with
      various dyes but also in living cells. Moreover, the HRP beam significantly
      extended the depth of field, which facilitated obtaining in-focus images,
      especially during time-lapse observations of living cells. These results indicate
      that our method is applicable to various biological applications. 

PMID- 24123930
TI  - Peroral pancreatoscopy using the SpyGlass system for the assessment of
      intraductal papillary mucinous neoplasm of the pancreas.
AB  - BACKGROUND: Peroral pancreatoscopy (POPS) using a mother-baby endoscope system is
      often useful for assessment of intraductal papillary mucinous neoplasm (IPMN) of
      the pancreas with main pancreatic duct (MPD) involvement, but is not widely used
      for several reasons. The aim of this study was to evaluate the usefulness of the
      SpyGlass Direct Visualization System for assessment of IPMN. METHODS: Seventeen
      patients diagnosed with possible IPMN with MPD dilation underwent peroral
      pancreatoscopy using the SpyGlass system at our institution. The quality of
      visualization and the sensitivities of cytological and pathological
      investigations for diagnosing malignant lesions were evaluated. RESULTS: Peroral
      pancreatoscopy was performed using the SpyScope in 12 patients and an endoscopic
      retrograde cholangiopancreatography (ERCP) catheter in five patients. Sufficient
      visualization was achieved in 92% of cases using the SpyScope and 40% of cases
      using the ERCP catheter. Biopsy under direct visualization was successful in
      seven patients. Biopsy specimens showed adenocarcinoma in one patient, benign
      neoplastic epithelium in five patients, and regenerative changes in one patient;
      and had 25% sensitivity and 100% specificity for detecting malignancy. SpyGlass
      pancreatoscopy with irrigation cytology had 100% sensitivity and 100% specificity
      for detecting malignancy. SpyGlass pancreatoscopy was useful for determining the
      operative excision line in three patients. There were no severe procedure-related
      adverse events. CONCLUSIONS: Peroral pancreatoscopy using the SpyGlass system
      seems to be feasible and useful for assessment of IPMN with a dilated MPD.

PMID- 24123932
TI  - Evaluation of six synthetic surgical meshes implanted subcutaneously in a rat
      model.
AB  - The long-term efficacy and mechanical integrity of implanted materials is largely
      determined by early host response. Therefore, implanting materials with well
      characterized tissue responses provides the greatest chance of 'one-hit' surgical
      successes, without repeated interventions to replace, repair or remove non
      compliant biomaterials. Six synthetic meshes were implanted subcutaneously in a
      rat model to deduce and quantify modulations in host response, based on material
      fabrication variables. The materials consisted of knitting variations of
      polypropylene (PP), polyethyleneterephthalate (PET) and polyglycolic acid (PGA)
      yarns and were implanted for 2, 5, 7, 14 and 28 days before fixation and both
      semi- and fully quantitative histopathology. In a subcutaneous niche, material
      weight did not influence foreign body response. PET stimulated earlier
      inflammation than PP and PGA, which normalized over 28 days. Multifilament meshes
      recruited foreign body giant cells, which were largely absent from monofilaments.
      Using CD68, PGA was demonstrated to be the greatest leukocyte-activating polymer
      at a number of the time points analysed. This research therefore highlights that
      underlying polymer composition may be more over-arching in deciding the
      inflammatory properties of surgical meshes, based on increased macrophagic
      responses to PGA vs alternative base polymers of comparable weights and
      porosities. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24123934
TI  - Reaction engineering strategies for the production of inorganic nanomaterials.
AB  - The rapid expansion of nanotechnology requires scaled-up production rates to cope
      with increased nanomaterials demand. However, in many cases, the final uses of
      nanomaterials impose strict requisites on their physical and chemical
      characteristics including size, shape, chemical composition and type of
      functional groups on their surface. Frequently, additional features such as a
      limited degree of agglomeration are also demanded. These requisites represent a
      serious challenge to present-day synthesis methods when nanomaterials must be
      produced in large amounts. Some of the possible solutions from the reaction
      engineering perspective are discussed in this work for both gas and liquid phase
      production processes. Special attention will be devoted to enabling technologies,
      which allow the production of engineered nanoparticles with limited aggregation
      and with a good control on their nano-scale characteristics. 

PMID- 24123935
TI  - Embryonic and larval neural connectivity: progressive changes in synapse form and
      function at the neuromuscular junction mediated by cytoskeletal regulation.
AB  - During development, precise formation of millions of synaptic connections is
      critical for the formation of a functional nervous system. Synaptogenesis is a
      complex multistep process in which axons follow gradients of secreted and cell
      surface guidance cues to reach their target area, at which point they must
      accurately distinguish their specific target. Upon target recognition, the axonal
      growth cone undergoes rapid growth and morphological changes, ultimately forming
      a functional synapse that continues to remodel during activity-dependent
      plasticity. Significant evidence suggests that the underlying actin and
      microtubule (MT) cytoskeletons are key effectors throughout synaptogenesis
      downstream of numerous receptors and signaling pathways. An increasing number of
      cytoskeletal-associated proteins have been shown to influence actin and MT
      stability and dynamics and many of these regulators have been implicated during
      synaptic morphogenesis using both mammalian and invertebrate model systems. In
      this review, we present an overview of the role cytoskeletal regulators play
      during the formation of the Drosophila neuromuscular junction.

PMID- 24123937
TI  - The many functions of mRNA localization during normal development and disease:
      from pillar to post.
AB  - The regulated intracellular trafficking and localized translation of mRNA
      molecules represents an important and prevalent mechanism of gene regulation.
      This process plays a key role in modulating asymmetric protein distribution
      linked to a wide variety of biological processes in different organisms and cell
      types. In this review, we begin by discussing the diverse biological functions,
      advantages, and mechanisms of mRNA localization that have been characterized to
      date. We then review recent technological innovations in RNA imaging and
      functional genomics methods that will undoubtedly provide powerful new strategies
      for the elucidation of mRNA trafficking pathways. Finally, we discuss several
      examples linking human disease pathogenesis to defects in transcript
      localization, which further underlines the critical importance of this gene
      regulatory mechanism.

PMID- 24123936
TI  - Building quantitative, three-dimensional atlases of gene expression and
      morphology at cellular resolution.
AB  - Animals comprise dynamic three-dimensional arrays of cells that express gene
      products in intricate spatial and temporal patterns that determine cellular
      differentiation and morphogenesis. A rigorous understanding of these
      developmental processes requires automated methods that quantitatively record and
      analyze complex morphologies and their associated patterns of gene expression at
      cellular resolution. Here we summarize light microscopy-based approaches to
      establish permanent, quantitative datasets-atlases-that record this information.
      We focus on experiments that capture data for whole embryos or large areas of
      tissue in three dimensions, often at multiple time points. We compare and
      contrast the advantages and limitations of different methods and highlight some
      of the discoveries made. We emphasize the need for interdisciplinary
      collaborations and integrated experimental pipelines that link sample
      preparation, image acquisition, image analysis, database design, visualization,
      and quantitative analysis.

PMID- 24123938
TI  - Cytoplasmic protein motility and polarized sorting during asymmetric cell
      division.
AB  - Cell polarity is inherent to the process of asymmetric cell division, which
      relies on the asymmetric distribution of multiple polarity proteins and cell-fate
      determinants in the cell cortex. The establishment and maintenance of cell
      polarity require the orchestration of numerous cellular processes. These include
      cytoplasmic movements, cytoskeleton dynamics, and different signaling events.
      Equally relevant is the plasma membrane composition, such as the lipid
      environment that endows particular membrane subdomains with specific
      characteristics. Sorting receptors and sorting determinants, including
      posttranslational modifications, also contribute to cell polarization. Together,
      all these mechanisms would be expected to have great relevance in the context of
      asymmetric cell division, an essential process in both physiological and
      pathological conditions.

PMID- 24123939
TI  - Phenotyping the kinematics of leaf development in flowering plants:
      recommendations and pitfalls.
AB  - Leaves of flowering plants are produced from the shoot apical meristem at regular
      intervals and they grow according to a developmental program that is determined
      by both genetic and environmental factors. Detailed frameworks for multiscale
      dynamic analyses of leaf growth have been developed in order to identify and
      interpret phenotypic differences caused by either genetic or environmental
      variations. They revealed that leaf growth dynamics are non-linearly and
      nonhomogeneously distributed over the lamina, in the leaf tissues and cells. The
      analysis of the variability in leaf growth, and its underlying processes, has
      recently gained momentum with the development of automated phenotyping platforms
      that use various technologies to record growth at different scales and at high
      throughput. These modern tools are likely to accelerate the characterization of
      gene function and the processes that underlie the control of shoot development.
      Combined with powerful statistical analyses, trends have emerged that may have
      been overlooked in low throughput analyses. However, in many examples, the
      increase in throughput allowed by automated platforms has led to a decrease in
      the spatial and/or temporal resolution of growth analyses. Concrete examples
      presented here indicate that simplification of the dynamic leaf system, without
      consideration of its spatial and temporal context, can lead to important
      misinterpretations of the growth phenotype.

PMID- 24123940
TI  - Supplementing cryopreservation media with reduced glutathione increases fertility
      and prolificacy of sows inseminated with frozen-thawed boar semen.
AB  - The main aim of this work was to evaluate how supplementing freezing media with
      reduced glutathione (GSH) affected the 'in vivo' fertilizing ability of boar
      semen subjected to cryopreservation procedures. With this purpose, 12 ejaculates
      coming from 12 boars were cryopreserved in the presence or absence of 2 mm GSH,
      whereas the same number of extended ejaculates coming from the same boars was
      used as negative/farm controls. Eight different sperm parameters (levels of free
      cysteine residues in sperm nucleoproteins, DNA fragmentation, sperm viability,
      acrosome-membrane integrity, intracellular peroxide and superoxide levels, and
      total and progressive sperm motility) were evaluated before freezing and after 30
      and 240 min of thawing. In addition, a total of 180 multiparous sows were used in
      the field fertility trials, the females being randomly divided into three groups
      and inseminated with extended, frozen-thawed control or frozen-thawed semen
      supplemented with 2 mm GSH. The presence of GSH in the freezing media
      significantly (p < 0.05) increased farrowing rates and the number of total born
      piglets and alive born piglets, and partially counteracted the cryopreservation
      induced damages inflicted on frozen-thawed spermatozoa. We can thus conclude that
      supplementing freezing media with 2 mm GSH greatly improves boar sperm
      cryopreservation technology, as it significantly improves the fertilizing ability
      of frozen-thawed spermatozoa. 

PMID- 24123941
TI  - Muscle area estimation from cortical bone.
AB  - This article investigates the relationship between the cortical bone of the
      radius and the muscle area of the forearm. The aim of this study was to develop a
      method for muscle area estimation from cortical bone area at 65% of radius length
      where the muscle area at the forearm is largest. Muscle area and cortical area
      were measured directly in vivo by peripheral Quantitative Computed Tomography
      (pQCT). We found significant correlations between muscle area and cortical area
      (r = 0.881) in the forearm that are in line with previous studies. We have set up
      a regression model by testing relevant parameters such as age, sex, forearm
      length, and stature that were all highly correlated to muscle area. The influence
      of age and sex on the proportion of muscle area to cortical area is strong and
      potentially related to the effects of testosterone and estrogen on the muscle
      bone-unit. Muscle area estimation from cortical bone is possible with a Percent
      Standard Error of Estimate (%SEE) ranging from 12.03% to 14.83%, depending on the
      parameters available and the age and sex of the individual. Muscle area
      estimation from cortical bone can provide new information for the study of
      skeletal and/or fossil human remains.

PMID- 24123942
TI  - Targeted proteomics strategy applied to biomarker evaluation.
AB  - The evaluation of biomarker candidates, involving quantitative measurement of a
      large number of proteins in bodily fluids, remains the main obstruction in the
      development of a biomarker validation pipeline. Although immunoassays are
      commonly used, high-throughput and multiplex-capable methods are required for
      expediting the evaluation process. MS-based approaches employing targeted
      proteomic strategies provide not only a sensitive, but in addition a precise
      quantification tool, which is versatile, systematic, and scalable. Its capability
      of multiplexing hundreds of targets facilitate a cost-effective and rapid
      evaluation and is especially useful during the early stage of the process where a
      large list of candidate biomarkers must be triaged before entering validation
      studies. The robustness requirement for the methods also mandates a high degree
      of selectivity to analyze complex clinical samples. Improvement in the
      selectivity of LC-MS methods has been achieved by adopting high-resolution and
      high-accuracy mass analyzers to perform quantitative analyses with a novel method
      called parallel reaction monitoring. This article discusses the design and
      performance of biomarker evaluation studies using targeted proteomics strategies
      and the implementation of recent technology developments. 

PMID- 24123943
TI  - Stress-sensor device based on flexoelectric liquid crystalline membranes.
AB  - Membrane flexoelectricity is an electromechanical coupling process that describes
      membrane bending and membrane electrical polarization caused by bending under
      electric fields. In this paper we propose, formulate, and characterize a stress
      sensor device for mechanically loaded solids, consisting of a soft flexoelectric
      thin membrane attached to the loaded deformed solid. Because the curvature of the
      deformed solid is transferred to the attached flexoelectric membrane, the
      electromechanical transduction of the latter produces a charge that is
      proportional to the stress of the solid. The model of the stress-sensor device is
      based on the integration of the thermodynamics of polarizable membranes with
      isotropic solid elasticity, leading to a transfer function that identifies the
      elastic, electromechanical, and geometrical parameters involved in electrical
      signal generation. The model is applied to representative normal bending and then
      to more complex off-axis bending of elastic bars. In all cases, a common transfer
      function shows the generic material and its geometric contributions. The sensor
      sensitivity increases linearly with flexoelectricity and the membrane-solid
      interface, and the sensitivity decreases with increasing membrane thickness and
      Young's modulus of the solid. The theoretical results contribute to ongoing
      experimental efforts towards the development of anisotropic soft-matter-based
      stress-sensor devices through solid-membrane interactions and electromechanical
      transduction. 

PMID- 24123944
TI  - Fourier transform microwave spectroscopy: handedness caught by rotational
      coherence.

PMID- 24123946
TI  - Genetic counseling for susceptibility loci and neurodevelopmental disorders: the
      del15q11.2 as an example.
AB  - In recent years, several recurrent copy number variations (CNVs) that confer risk
      of neurodevelopmental disorders have been identified (e.g., del and dup 16p11.2,
      del15q13.3, del and dup 1q21.1, del16p13.3, del15q11.2). They are often inherited
      from an unaffected parent and lack phenotypic specificity. Although there is
      growing evidence from association studies to consider them as susceptibility
      CNVs, their clinical utility is debated. Yet the clinician is frequently
      challenged to deal with these counseling situations without guidelines or
      consensus. In this report, counseling issues and research opportunities are
      discussed, with the recurrent 15q11.2 BP1-BP2 (including CYFIP1, NIPA1, NIPA2,
      TUBGCP5) as an example. Several clinical reports have been published describing
      patients with del15q11.2 featuring intellectual disability, developmental delay,
      neurological problems, autism spectrum disorder (ASD), attention problems, speech
      delay, and dysmorphism. The del15q11.2 was found to be significantly associated
      with intellectual disability, schizophrenia, epilepsy, and ASD. In this report we
      discuss how patient-specific and family-specific information may alter the
      interpretation of del15q11.2 as a contributing factor to the disorder in
      practical counseling situations. In addition, an association study for ASD in a
      Belgian Flemish cohort and an overview of reported association studies, clinical
      reports and genomics data for del15q11.2 are presented.

PMID- 24123947
TI  - Numerical investigation of biomagnetic fluids in circular ducts.
AB  - A mathematical model for the description of biomagnetic fluid flow exposed to a
      magnetic field that accounts for both electric and magnetic properties of the
      biofluid is presented. This is achieved by adding the Lorentz and magnetization
      forces in the Navier-Stokes equations. To demonstrate the effects of magnetic
      fields, we consider the case of laminar, incompressible, viscous, the steady flow
      of a Newtonian biomagnetic fluid (i) between two parallel plates; and (ii)
      through a straight rigid tube with a 60% in diameter, 84% on area, axisymmetric
      stenosis. Two external magnetic fields were investigated: one produced by an
      infinite wire carrying constant current, and a dipole-like field. We show,
      numerically and analytically, that the wire produces an irrotational force that,
      independent of its intensity, only alters the pressure leaving the velocity field
      unaffected. In contrast, when the fluid is exposed to the dipole-like field,
      which generates a rotational force, then both pressure and velocity can be
      strongly influenced even at moderate field strengths. Similar trends were
      obtained when a time varying flow is simulated through the axisymmetric stenosis
      in the presence of the dipole-like rotational magnetic field. It is expected that
      our findings could have important applications in blood flow control.

PMID- 24123945
TI  - Modifying effect of obesity on the association between sitting and incident
      diabetes in post-menopausal women.
AB  - OBJECTIVE: To evaluate the association between self-reported daily sitting time
      and the incidence of type 2 diabetes in a cohort of postmenopausal women.
      METHODS: Women (N=88,829) without diagnosed diabetes reported the number of hours
      spent sitting over a typical day. Incident cases of diabetes were identified
      annually by self-reported initiation of using oral medications or insulin for
      diabetes > 14.4 years follow-up. RESULTS: Each hour of sitting time was
      positively associated with increased risk of diabetes [risk ratio (RR): 1.05; 95%
      confidence interval (CI): 1.02-1.08]. However, sitting time was only positively
      associated with incident diabetes in obese women. Obese women reporting sitting 8
      11 (RR: 1.08; 95% CI 1.0-1.1), 12-15 (OR: 1.13; 95% CI 1.0-1.2), and >=16 hours
      (OR: 1.25; 95% CI 1.0-1.5) hours per day had an increased risk of diabetes
      compared to women sitting <=7 hours per day. These associations were adjusted for
      demographics, health conditions, behaviors (smoking, diet, and alcohol intake),
      and family history of diabetes. Time performing moderate to vigorous intensity
      physical activity did not modify these associations. CONCLUSIONS: Time spent
      sitting was independently associated with increased risk of diabetes diagnosis
      among obese women-a population already at high risk of the disease.

PMID- 24123948
TI  - How might ZNF804A variants influence risk for schizophrenia and bipolar disorder?
      A literature review, synthesis, and bioinformatic analysis.
AB  - The gene that encodes zinc finger protein 804A (ZNF804A) became a candidate risk
      gene for schizophrenia (SZ) after surpassing genome-wide significance thresholds
      in replicated genome-wide association scans and meta-analyses. Much remains
      unknown about this reported gene expression regulator; however, preliminary work
      has yielded insights into functional and biological effects of ZNF804A by
      targeting its regulatory activities in vitro and by characterizing allele
      specific interactions with its risk-conferring single nucleotide polymorphisms
      (SNPs). There is now strong epidemiologic evidence for a role of ZNF804A
      polymorphisms in both SZ and bipolar disorder (BD); however, functional links
      between implicated variants and susceptible biological states have not been
      solidified. Here we briefly review the genetic evidence implicating ZNF804A
      polymorphisms as genetic risk factors for both SZ and BD, and discuss the
      potential functional consequences of these variants on the regulation of ZNF804A
      and its downstream targets. Empirical work and predictive bioinformatic analyses
      of the alternate alleles of the two most strongly implicated ZNF804A
      polymorphisms suggest they might alter the affinity of the gene sequence for DNA-
      and/or RNA-binding proteins, which might in turn alter expression levels of the
      gene or particular ZNF804A isoforms. Future work should focus on clarifying the
      critical periods and cofactors regulating these genetic influences on ZNF804A
      expression, as well as the downstream biological consequences of an imbalance in
      the expression of ZNF804A and its various mRNA isoforms.

PMID- 24123949
TI  - On the use of dexamethasone-loaded liposomes to induce the osteogenic
      differentiation of human mesenchymal stem cells.
AB  - Stem cells have received considerable attention by the scientific community
      because of their potential for tissue engineering and regenerative medicine. The
      most frequently used method to promote their differentiation is supplementation
      of the in vitro culture medium with growth/differentiation factors (GDFs). The
      limitations of that strategy caused by the short half-life of GDFs limit its
      efficacy in vivo and consequently its clinical use. Thus, the development of new
      concepts that enable the bioactivity and bioavailability of GDFs to be protected,
      both in vitro and in vivo, is very relevant. Nanoparticle-based drug delivery
      systems can be injected, protect the GDFs and enable spatiotemporal release
      kinetics to be controlled. Liposomes are well-established nanodelivery devices
      presenting significant advantages, viz. a high load-carrying capacity, relative
      safety and easy production, and a versatile nature in terms of possible
      formulations and surface functionalization. The main objective of the present
      study was to optimize the formulation of liposomes to encapsulate dexamethasone
      (Dex). Our results showed that the optimized Dex-loaded liposomes do not have any
      cytotoxic effect on human bone marrow-derived mesenchymal stem cells (hBMSCs).
      More importantly, they were able to promote an earlier induction of
      differentiation of hBMSCs into the osteogenic lineage, as demonstrated by the
      expression of osteoblastic markers, both phenotypically and genotypically. We
      concluded that Dex-loaded liposomes represent a viable nanoparticle strategy with
      enhanced safety and efficacy for tissue engineering and regenerative medicine.

PMID- 24123955
TI  - Applications of cell-free protein synthesis in synthetic biology: Interfacing bio
      machinery with synthetic environments.
AB  - Synthetic biology is built on the synthesis, engineering, and assembly of
      biological parts. Proteins are the first components considered for the
      construction of systems with designed biological functions because proteins carry
      out most of the biological functions and chemical reactions inside cells. Protein
      synthesis is considered to comprise the most basic levels of the hierarchical
      structure of synthetic biology. Cell-free protein synthesis has emerged as a
      powerful technology that can potentially transform the concept of bioprocesses.
      With the ability to harness the synthetic power of biology without many of the
      constraints of cell-based systems, cell-free protein synthesis enables the rapid
      creation of protein molecules from diverse sources of genetic information. Cell
      free protein synthesis is virtually free from the intrinsic constraints of cell
      based methods and offers greater flexibility in system design and manipulability
      of biological synthetic machinery. Among its potential applications, cell-free
      protein synthesis can be combined with various man-made devices for rapid
      functional analysis of genomic sequences. This review covers recent efforts to
      integrate cell-free protein synthesis with various reaction devices and
      analytical platforms. 

PMID- 24123956
TI  - Study on the synthesis and structure-effect relationship of multi-aryl imidazoles
      with their fluorescence properties.
AB  - In this paper, 23 multi-aryl imidazole derivatives were synthesized and
      identified by nuclear magnetic resonance, ultraviolet-visible and elemental
      analysis. At the same time, their ultraviolet-visible maximum absorption
      (lambda(ab)(max)), fluorescence emission maximum (lambda(em)(max)) and quantum
      yields (F(f)) were measured. The relationships between the optical behaviors and
      structures for these compounds were assessed. The results show that the
      lambda(max)(ab) and lambda(max)(em) are red-shifted and the fluorescence F(f) are
      increased by the introduction of electron-withdrawing substituents and the
      increase in the planarity of multi-aryl imidazole molecules. The results also
      showed that the fluorescence quantum yields of the compounds containing two
      imidazole nuclei are double the corresponding mono-imidazole nucleus compounds.

PMID- 24123957
TI  - Cytotoxicity of PVPAC-treated bovine pericardium: a potential replacement for
      glutaraldehyde in biological heart valves.
AB  - Acellular biological tissues, including bovine pericardium (BP), have been
      proposed as biomaterial for tissue engineering. BP is usually modified chemically
      to improve mechanical and biological properties using glutaraldehyde, the
      standard reagent for preservation of fresh bioprosthetic materials.
      Glutaraldehyde-fixed BP (Glut-BP), the most widely used material in heart valve
      manufacture, has been associated with calcification in vivo. In an attempt to
      reduce this issue and maintain its biocompatibility, this study assesses the
      physical properties and cytotoxicity of lyophilized BP treated with poly
      (vinylpyrrolidone-co-acrolein) (PVPAC-BP), a novel copolymer, as a substitute for
      glutaraldehyde. For that, PVPAC-BP surface ultrastructure, elastic function,
      water uptake and tissue calcification were evaluated. For the analysis of
      biocompatibility, fibroblasts (3T3-L1) and endothelial cells (HUVEC) were
      cultured on PVPAC-BP, Untreated-BP and Glut-BP. Nitric oxide (NO) release assay,
      fluorescence and SEM images of endothelial cells adhered on scaffolds were also
      performed. As results, the data show some advantages of PVPAC-BP over the Glut
      BP. The PVPAC-BP maintains partially the original ultrastructure and elastic
      properties, improves scaffold hydration, and presents less calcium phosphate
      deposits. The cells demonstrated strong attachment, high proliferation rate, and
      formation of a monolayer on PVPAC-BP. Attached cells were also able to release NO
      de-monstrating regular metabolism. In conclusion, PVPAC may be considered as a
      promising alternative to BP treatment improving the efficiency of cell attachment
      and proliferation and also avoid immunogenicity.

PMID- 24123959
TI  - Design of experiments applications in bioprocessing: concepts and approach.
AB  - Most biotechnology unit operations are complex in nature with numerous process
      variables, feed material attributes, and raw material attributes that can have
      significant impact on the performance of the process. Design of experiments (DOE)
      based approach offers a solution to this conundrum and allows for an efficient
      estimation of the main effects and the interactions with minimal number of
      experiments. Numerous publications illustrate application of DOE towards
      development of different bioprocessing unit operations. However, a systematic
      approach for evaluation of the different DOE designs and for choosing the optimal
      design for a given application has not been published yet. Through this work we
      have compared the I-optimal and D-optimal designs to the commonly used central
      composite and Box-Behnken designs for bioprocess applications. A systematic
      methodology is proposed for construction of the model and for precise prediction
      of the responses for the three case studies involving some of the commonly used
      unit operations in downstream processing. Use of Akaike information criterion for
      model selection has been examined and found to be suitable for the applications
      under consideration.

PMID- 24123958
TI  - Neodymium-doped LaF(3) nanoparticles for fluorescence bioimaging in the second
      biological window.
AB  - The future perspective of fluorescence imaging for real in vivo application are
      based on novel efficient nanoparticles which is able to emit in the second
      biological window (1000-1400 nm). In this work, the potential application of
      Nd(3+) -doped LaF(3) (Nd(3+) :LaF(3) ) nanoparticles is reported for fluorescence
      bioimaging in both the first and second biological windows based on their three
      main emission channels of Nd(3+) ions: (4) F(3/2) ->(4) I(9/2) , (4) F(3/2) ->(4)
      I(11/2) and (4) F(3/2) ->(4) I(13/2) that lead to emissions at around 910, 1050,
      and 1330 nm, respectively. By systematically comparing the relative emission
      intensities, penetration depths and subtissue optical dispersion of each
      transition we propose that optimum subtissue images based on Nd(3+) :LaF(3)
      nanoparticles are obtained by using the (4) F3/2 ->(4) I11/2 (1050 nm) emission
      band (lying in the second biological window) instead of the traditionally used
      (4) F(3/2) ->(4) I(9/2) (910 nm, in the first biological window). After
      determining the optimum emission channel, it is used to obtain both in vitro and
      in vivo images by the controlled incorporation of Nd(3+) :LaF(3) nanoparticles in
      cancer cells and mice. Nd(3+) :LaF(3)nanoparticles thus emerge as very promising
      fluorescent nanoprobes for bioimaging in the second biological window.

PMID- 24123960
TI  - Cause-specific effects of radiotherapy and lymphadenectomy in stage I-II
      endometrial cancer: a population-based study.
AB  - BACKGROUND: Radiotherapy and lymphadenectomy have been associated with improved
      survival in population-based studies of endometrial cancer, which is in contrast
      with findings from randomized trials and meta-analyses. The primary study aim was
      to estimate the cause-specific effects of adjuvant radiotherapy and
      lymphadenectomy on competing causes of mortality. METHODS: We analyzed
      Surveillance, Epidemiology, and End Results (SEER) data from 1988 to 2006. The
      sample comprised 58172 patients with stage I and II endometrial adenocarcinoma.
      Patients were risk stratified by stage, grade, and age. Cumulative incidences and
      cause-specific hazards of competing causes of mortality were estimated according
      to treatment. All statistical tests were two-sided. RESULTS: Pelvic radiotherapy
      was associated with statistically significantly increased endometrial cancer
      mortality (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.52 to 1.82)
      in all stage I and II patients and decreased noncancer mortality in intermediate
      and high-risk stage I and II patients (HR = 0.82; 95% CI = 0.77 to 0.89).
      Lymphadenectomy was associated with increased endometrial cancer mortality in
      stage I patients (HR = 1.27; 95% CI = 1.16 to 1.39), decreased endometrial cancer
      mortality in stage II patients (HR = 0.61; 95% CI = 0.52 to 0.72), and decreased
      noncancer mortality in both stage I and II patients (HR = 0.84; 95% CI = 0.80 to
      0.88). Effects of radiotherapy and lymphadenectomy on second cancer mortality
      varied according to risk strata. CONCLUSIONS: Radiotherapy and lymphadenectomy
      are associated with statistically significantly reduced noncancer mortality in
      stage I and II endometrial cancer. The improved overall survival associated with
      these treatments reported from SEER studies is largely attributable to their
      selective application in healthier patients rather than their effects on
      endometrial cancer.

PMID- 24123961
TI  - Paramagnetic inorganic nanoparticles as T1 MRI contrast agents.
AB  - Magnetic resonance imaging (MRI) is one of the most powerful molecular imaging
      techniques and can noninvasively visualize and quantify biological processes
      within the living organisms. The introduction of exogenous contrast agents has
      allowed specific visualization of biological targets as well as enhanced the
      sensitivity of MRI. Recently, paramagnetic inorganic nanoparticles showing
      positive T(1) contrast effect have been investigated as T(1) MRI contrast agents.
      Since the first trials of spherical nanoparticles of manganese oxide and
      gadolinium oxide, inorganic nanoparticles of various compositions and shapes have
      been used for in vivo and in vitro MRI because of their distinct signal
      enhancement in MR images. However, for clinical applications, important and
      complex issues such as safety and efficiency should be investigated by active
      research encompassing multiple disciplines, including chemistry, biology,
      biomedical engineering, and medicine.

PMID- 24123962
TI  - Differentiation of myxoid liposarcoma by magnetic resonance imaging: a
      histopathologic correlation.
AB  - BACKGROUND: Myxoid liposarcomas represent a heterogeneous group of soft tissue
      tumors in which prognosis is dependent on differentiation. PURPOSE: To identify
      magnetic resonance imaging (MRI) criteria to distinguish low-grade from high
      grade myxoid liposarcomas. MATERIAL AND METHODS: MR images of 30 histologically
      proven myxoid liposarcomas were retrospectively reviewed. Tumors were evaluated
      according to size, localization, tumor border, and structure as well as tumor
      composition. These imaging criteria were correlated with histopathological
      findings. RESULTS: Nineteen myxoid liposarcomas were histologically classified as
      low-grade myxoid liposarcomas, whereas 11 were considered high-grade myxoid
      liposarcomas. Mean tumor volume of low-grade myxoid liposarcomas (710.1 +/- 960.1
      ccm) was significantly smaller as compared to high-grade myxoid liposarcomas
      (2737.0 +/- 3423.7 ccm; P = 0.04). In addition to necrotic areas, three tumor
      components - fatty, myxoid, as well as contrast-enhancing non-fatty, non-myxoid -
      could be identified. The mean fraction of fatty tumor areas in low-grade myxoid
      liposarcomas was 10 +/- 11% as compared to 6 +/- 4% for high-grade myxoid
      liposarcomas (P = 0.66). Myxoid components accounted for 88 +/- 16% in low-grade
      myxoid liposarcomas, but only for 45 +/- 25% in high-grade myxoid liposarcomas (P
      < 0.0001). The non-fatty, non-myxoid tumor fraction was significantly higher in
      high-grade myxoid liposarcomas (50 +/- 25%) as compared to low-grade myxoid
      liposarcomas (2 +/- 9%; P < 0.0001). A proportion of > 5% of this tumor fraction
      was found to be a precise unique predictor for high-grade myxoid liposarcomas
      with a sensitivity of 100% and a specificity of 95%. CONCLUSION: Tumor components
      with contrast-enhancing non-fatty, non-myxoid imaging features were predominantly
      found in high-grade myxoid liposarcomas, which may histologically resemble round
      cell clusters.

PMID- 24123963
TI  - Segmentation features and structural organization of the intrapulmonary artery of
      the yak.
AB  - This study aims to systematically investigate intrapulmonary artery segmentation,
      blood vessel wall characteristics and structure organization, and the
      interrelation between intrapulmonary artery structure and plateau hypoxia
      adaptation in yak. The normal intrapulmonary artery structure of the yak had been
      studied using histological methods and transmission electron microscopy. The
      intrapulmonary artery of the yak was also examined using morphometric analysis
      and angiography. Results showed that the elastic intrapulmonary artery is divided
      into two types, namely, classical and transitional elastic segments. The muscular
      intrapulmonary artery is divided into three types, namely, transitional,
      classical muscular, and muscular arteriole segments. In the transitional elastic
      artery, elastic fibers and smooth muscles are linked through three models of
      ends, lateral branches, and branch tops. Two phenomena are possible for the
      transition from the elastic intrapulmonary artery to the muscular artery. One
      phenomenon postulates that a less elastic membrane is first increased and then
      suddenly decreased, and another supposes that the elastic membrane is gradually
      reduced and assembled in one to two layers before entering the transitional
      muscular artery. The smooth muscle of the intrapulmonary artery tunica media had
      more apophysis; it was physically connected with elastic membrane or fiber and
      composed of functionally resilient unit of the intrapulmonary arterial wall.
      Glycogenosomes increased in the muscular intrapulmonary artery smooth muscle
      cells. It exist one to two layers intact smooth muscle in intrapulmonary
      arteriole, the presence of intact smooth muscle in the intrapulmonary arteriole
      of the yak is a kind of structure adaptation to low-oxygen environment.

PMID- 24123964
TI  - Determining the critical particle size to induce enhanced emission in aggregates
      of a highly twisted triarylamine.
AB  - Towards highly luminescent aggregates: A highly twisted triphenylamine displays
      aggregation-induced enhanced emission. A solvent-specific critical molecular
      aggregate size, once reached, gives rapid onset of enhanced emission in polar
      solvent mixtures that favor quenching of solvated individual molecule excited
      states. 

PMID- 24123965
TI  - MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in
      microorganisms.
AB  - MALDI-TOF MS profiling for microorganism detection has already been demonstrated
      in the 1990s, but has evolved to the first-line identification method in many
      laboratories just during the past five years. While this application of MALDI-TOF
      MS has proven its broad applicability, accuracy, robustness, and cost
      effectiveness it is of particular interest to expand the capabilities of the mass
      spectrometric platform. Resistance detection is the most desirable further
      application of MALDI-TOF MS in microbiology, but maybe also the most challenging.
      Different approaches have been published regarding diverse antibiotic drugs and
      distinct microorganism classes. The current review shall give an overview about
      the developments of the recent years and their potential to get transformed in
      clinical useful assays in the future. 

PMID- 24123966
TI  - Polysomnographic findings in infantile Pompe disease.
AB  - Infantile Pompe disease is a rare, autosomal recessive disorder due to deficiency
      of the enzyme acid alpha-glucosidase that degrades lysosomal glycogen. Clinical
      features of diffuse hypotonia, cardiomyopathy, and weakness are present within
      the first days to months of life in patients with classic infantile Pompe
      disease. Progression of the disease often leads to respiratory failure. Although
      sleep apnea is reported in late-onset Pompe disease, sleep pathology is not well
      characterized in infantile disease. In this retrospective study, we analyzed
      nocturnal polysomnography results from 17 patients with infantile-onset Pompe
      disease. Obstructive sleep apnea and hypoventilation were common among this
      cohort, even in those that did not have symptoms of sleep-disordered breathing.
      All patients with infantile-onset Pompe disease should undergo polysomnography as
      a routine part of their care.

PMID- 24123968
TI  - Methylenetetrahydrofolate reductase (MTHFR) genetic variation and major
      depressive disorder prognosis: A five-year prospective cohort study of primary
      care attendees.
AB  - Methylenetetrahydrofolate reductase (MTHFR) genetic variation has been associated
      with the diagnosis of major depressive disorder (MDD) but no study to date has
      examined the effect MTHFR variation has on MDD prognosis. We sought to examine
      the prospective effects of two common MTHFR variants (C677T and A1298C) as well
      as seven haplotype-tagging single nucleotide polymorphisms (htSNPs) on MDD
      prognosis over a 5-year (60-month) period. Participants were 147 depressed
      primary care attendees enrolled in the Diagnosis, Management and Outcomes of
      Depression in Primary Care (diamond) prospective cohort study. Prognosis of MDD
      was measured using three methods: (1) DSM-IV criteria, (2) Primary Care
      Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3)
      Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria for MDD
      was assessed using the Composite International Diagnostic Interview at baseline
      and 24, 36, 48, and 60 months post-baseline; whereas, PHQ-9 and CESD measures
      were employed at baseline and 12, 24, 36, 48, and 60 months post-baseline.
      Repeated measures analysis of variance showed that PHQ-9 symptom severity
      trajectories differed by C677T genotype (F = 3.34, df = 2,144, P = 0.038), with
      677CC genotype showing the most severe symptom severity course over the 60 months
      of observation. Neither the A1298C polymorphism nor any of the htSNPs were
      associated with MDD prognosis regardless of measure used. Our results suggest
      that the MTHFR C677T polymorphism may serve as a marker for MDD prognosis pending
      independent replication.

PMID- 24123967
TI  - Hepatic insulin clearance is the primary determinant of insulin sensitivity in
      the normal dog.
AB  - OBJECTIVE: Insulin resistance is a powerful risk factor for Type 2 diabetes and a
      constellation of chronic diseases, and is most commonly associated with obesity.
      We examined if factors other than obesity are more substantial predictors of
      insulin sensitivity under baseline, nonstimulated conditions. METHODS: Metabolic
      assessment was performed in healthy dogs (n = 90). Whole-body sensitivity from
      euglycemic clamps (SICLAMP ) was the primary outcome variable, and was measured
      independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and
      glucose-stimulated insulin response was measured from hyperglycemic clamp or
      IVGTT (n = 86 and 36, respectively). RESULTS: SICLAMP was highly variable (5.9
      75.9 dl/min per kg per MUU/ml). Despite narrow range of body weight (mean, 28.7
      +/- 0.3 kg), adiposity varied approximately eight-fold and was inversely
      correlated with SICLAMP (P < 0.025). SICLAMP was negatively associated with
      fasting insulin, but most strongly associated with insulin clearance. Clearance
      was the dominant factor associated with sensitivity (r = 0.53, P < 0.00001),
      whether calculated from clamp or IVGTT. CONCLUSIONS: These data suggest that
      insulin clearance contributes substantially to insulin sensitivity, and may be
      pivotal in understanding the pathogenesis of insulin resistance. We propose the
      hyperinsulinemia due to reduction in insulin clearance is responsible for insulin
      resistance secondary to changes in body weight.

PMID- 24123970
TI  - The Nozoe Autograph Books: Stories behind the Stories.
AB  - Nozoe book signatories: The signatures of 14 chemists are presented along with
      anecdotal commentaries on the circumstances and research that went into their
      signing of the Nozoe Autograph Books (shown top (l to r): Sir Derek Barton, Carl
      Djerassi, Albert Eschenmoser; bottom (l to r): Roald Hoffmann, Rolf Gleiter,
      Ryoji Noyori). This Essay and the interactive website that accompanies the Nozoe
      Autograph Book project are available free-access for a three-year period at
      http://www.tcr.wiley-vch.de/nozoe.

PMID- 24123969
TI  - Multiscale approach including microfibril scale to assess elastic constants of
      cortical bone based on neural network computation and homogenization method.
AB  - The complexity and heterogeneity of bone tissue require a multiscale modeling to
      understand its mechanical behavior and its remodeling mechanisms. In this paper,
      a novel multiscale hierarchical approach including microfibril scale based on
      hybrid neural network (NN) computation and homogenization equations was developed
      to link nanoscopic and macroscopic scales to estimate the elastic properties of
      human cortical bone. The multiscale model is divided into three main phases: (i)
      in step 0, the elastic constants of collagen-water and mineral-water composites
      are calculated by averaging the upper and lower Hill bounds; (ii) in step 1, the
      elastic properties of the collagen microfibril are computed using a trained NN
      simulation. Finite element calculation is performed at nanoscopic levels to
      provide a database to train an in-house NN program; and (iii) in steps 2-10 from
      fibril to continuum cortical bone tissue, homogenization equations are used to
      perform the computation at the higher scales. The NN outputs (elastic properties
      of the microfibril) are used as inputs for the homogenization computation to
      determine the properties of mineralized collagen fibril. The mechanical and
      geometrical properties of bone constituents (mineral, collagen, and cross-links)
      as well as the porosity were taken in consideration. This paper aims to predict
      analytically the effective elastic constants of cortical bone by modeling its
      elastic response at these different scales, ranging from the nanostructural to
      mesostructural levels. Our findings of the lowest scale's output were well
      integrated with the other higher levels and serve as inputs for the next higher
      scale modeling. Good agreement was obtained between our predicted results and
      literature data.

PMID- 24123971
TI  - Hydrothermal fabrication of ZSM-5 zeolites: biocompatibility, drug delivery
      property, and bactericidal property.
AB  - The bone graft-associated infection is widely considered in orthopedic surgery,
      which may lead to implant failure, extensive bone debridement, and increased
      patient morbidity. In this study, we fabricated ZSM-5 zeolites for drug delivery
      systems by hydrothermal method. The structure, morphology, biocompatibility, drug
      delivery property, and bactericidal property of the ZSM-5 zeolites were
      investigated. The ZSM-5 zeolites have mordenite framework inverted-type structure
      and exhibit the disk-like shape with the diameter of ~350 nm and thickness of
      ~165 nm. The biocompatibility tests indicate that human bone marrow stromal cells
      spread out well on the surfaces of the ZSM-5 zeolites and proliferate
      significantly with increasing culture time. As compared with the conventional
      hydroxyapatite particles, the ZSM-5 zeolites possess greater drug loading
      efficiency and drug sustained release property because of the ordered micropores,
      large Brunauer-Emmett-Teller (BET) surface areas, and functional groups. For the
      gentamicin-loaded ZSM-5 zeolites, the sustained release of gentamicin minimizes
      significantly bacterial adhesion and prevents biofilm formation against
      Staphylococcus epidermidis. The excellent biocompatibility, drug delivery
      property, and bactericidal property of the ZSM-5 zeolites suggest that they have
      great application potentials for treating implant-associated infections.

PMID- 24123972
TI  - Current developments in high-throughput analysis for microalgae cellular
      contents.
AB  - Microalgae have emerged as one of the most promising feedstocks for biofuels and
      bio-based chemical production. However, due to the lack of effective tools
      enabling rapid and high-throughput analysis of the content of microalgae biomass,
      the efficiency of screening and identification of microalgae with desired
      functional components from the natural environment is usually quite low.
      Moreover, the real-time monitoring of the production of target components from
      microalgae is also difficult. Recently, research efforts focusing on overcoming
      this limitation have started. In this review, the recent development of high
      throughput methods for analyzing microalgae cellular contents is summarized. The
      future prospects and impacts of these detection methods in microalgae-related
      processing and industries are also addressed. 

PMID- 24123973
TI  - Optimization of five environmental factors to increase beta-propeller phytase
      production in Pichia pastoris and impact on the physiological response of the
      host.
AB  - Recently, we engineered Pichia pastoris Mut(s) strains to produce several beta
      propeller phytases, one from Bacillus subtilis and the others designed by a
      structure-guided consensus approach. Furthermore, we demonstrated the ability of
      P. pastoris to produce and secrete these phytases in an active form in shake
      flask cultures. In the present work, we used a design of experiments strategy
      (Simplex optimization method) to optimize five environmental factors that define
      the culture conditions in the induction step to increase beta-propeller phytase
      production in P. pastoris bioreactor cultures. With the optimization process, up
      to 347,682 U (82,814 U/L or 6.4 g/L culture medium) of phytase at 68 h of
      induction was achieved. In addition, the impact of the optimization process on
      the physiological response of the host was evaluated. The results indicate that
      the increase in extracellular phytase production through the optimization process
      was correlated with an increase in metabolic activity of P. pastoris, shown by an
      increase in oxygen demand and methanol consumption, that increase the specific
      growth rate. The increase in extracellular phytase production also occurred with
      a decrease in extracellular protease activity. Moreover, the optimized culture
      conditions increased the recombinant protein secretion by up to 88%, along with
      the extracellular phytase production efficiency per cell.

PMID- 24123974
TI  - A new quaternary photoluminescence enhancement system of Eu-N-(o-vanillin)-1,8
      diaminonaphthalene-1,10-phenanthroline-Zn and its application in determining
      trace amounts of europium and zinc.
AB  - A new sensitive quaternary photoluminescence enhancement system has been
      successfully developed to determine trace amounts of Eu(3+) and Zn(2+). The
      photoluminescence intensity of Eu - N-(o-vanilin)-1,8-diaminonaphthalene systems
      was greatly increased by the addition of specific concentrations of 1, 10
      phenanthroline and Zn(2+). The excitation and emission wavelengths were 274 and
      617 nm, respectively. Under optimal system conditions, the photoluminescence
      intensity showed a linear response toward Eu(3+) in the range of 5.0 * 10(-6)  ~
      2.0 * 10(-5)  M with a limit of detection (= 2.2 * 10(-9)  M) and the
      photoluminescence intensity of the system decreased linearly by increasing the
      Zn(2+) concentration in the range of 5.0 * 10(-8)  ~ 1.0 * 10(-6)  M with a limit
      of detection (= 8.8 * 10(-11)  M). This system was successfully applied for the
      determination of trace amounts of Eu(3+) in a high purity La2O3 matrix and in the
      synthetic rare earth oxide mixture, and of Zn(2+) in a high purity Mg(NO3)2 .
      6H2O matrix and in synthetic coexisting ionic matrixes. The energy transfer
      mechanism, photoluminescence enhancement of the system and interference of other
      lanthanide ions and common coexisting ions were also studied in detail.

PMID- 24123976
TI  - 2-Photon excitation fluorescence microscopy enables deeper high-resolution
      imaging of voltage and Ca(2+) in intact mice, rat, and rabbit hearts.
AB  - We describe a novel two-photon (2P) laser scanning microscopy (2PLSM) protocol
      that provides ratiometric transmural measurements of membrane voltage (Vm ) via
      Di-4-ANEPPS in intact mouse, rat and rabbit hearts with subcellular resolution.
      The same cells were then imaged with Fura-2/AM for intracellular Ca(2+)
      recordings. Action potentials (APs) were accurately characterized by 2PLSM vs.
      microelectrodes, albeit fast events (<1 ms) were sub-optimally acquired by 2PLSM
      due to limited sampling frequencies (2.6 kHz). The slower Ca(2+) transient (CaT)
      time course (>1ms) could be accurately described by 2PLSM. In conclusion, Vm -
      and Ca(2+) -sensitive dyes can be 2P excited within the cardiac muscle wall to
      provide AP and Ca(2+) signals to ~400 um.

PMID- 24123978
TI  - Laser-capture microdissection.

PMID- 24123979
TI  - Cord blood levels of osteopontin as a phenotype marker of gestational age and
      neonatal morbidities.
AB  - OBJECTIVES: Osteopontin (OPN) is a proinflammatory cytokine associated with
      metabolic syndrome. Extreme birth weight categories including small for
      gestational age (SGA), and large for gestational age (LGA) are risk factors for
      metabolic syndrome. However normal levels of plasma OPN in neonates and the
      relationship of OPN to fetal growth remain unknown. We evaluated the association
      of umbilical cord blood OPN with gestational age, birth weight, and neonatal
      outcomes. METHODS: A cross-sectional study of 261 newborns of all gestational
      ages beginning at week 26, and 26 adults for comparison was performed. Umbilical
      cord blood from newborns and analyzed plasma for OPN by ELISA was collected.
      RESULTS: Plasma OPN was significantly higher in neonates (414.65 +/- 136.72
      ng/mL) compared to adults (33.37 +/- 14.66 ng/mL, P < 0.001). There was an
      inverse correlation between OPN and gestational age (r = -0.48, P < 0.0001). LGA
      infants had lower OPN than appropriate for gestational age (AGA) infants, but LGA
      was not an independent predictor of OPN in multivariate analysis. Among preterm
      infants, patent ductus arteriosus (PDA) was independently associated with higher
      OPN (OR = 2.49, P = 0.02). CONCLUSION: Our results raise the possibility that OPN
      has a physiologic role in fetal growth and development, and may be a useful
      biomarker for PDA.

PMID- 24123980
TI  - Macroscale colloidal noble metal nanocrystal arrays and their refractive index
      based sensing characteristics.
AB  - Colloidal noble metal nanocrystals are promising for a large number of optical
      and biotechnological applications. Many practical applications require the
      formation of large-area, high-density, and uniformly distributed metal
      nanocrystal arrays on various substrates, to overcome the limitations brought by
      the instability of colloidal metal nanocrystal solutions and the high cost of
      single-particle spectroscopy characterizations. A method is developed for
      directly depositing colloidal metal nanocrystals, including Au nanospheres, Au
      nanorods, Au nanobipyramids, and (Au core)/(Ag shell) nanorods, from their
      solutions onto different substrates. The resultant nanocrystal arrays are
      relatively uniform and dense, with the peak extinction value of a single layer
      reaching 0.3. Their areas are up to 10 cm by 10 cm and can be further increased
      if larger-size containers are utilized. The refractive index sensitivities are
      studied for Au nanorod arrays supported on glass slides, mesoporous silica and
      titania films, and capped with different molecules. Au nanorods deposited on
      mesoporous titania films are found to exhibit the highest index sensitivities,
      comparable to those of the same nanorod sample in solutions. It is expected that
      this approach will greatly facilitate plasmonic applications that require large
      area arrays of noble metal nanocrystals. 

PMID- 24123977
TI  - Understanding engineered nanomaterial skin interactions and the modulatory
      effects of ultraviolet radiation skin exposure.
AB  - The study of engineered nanomaterials for the development of technological
      applications, nanomedicine, and nano-enabled consumer products is an ever
      expanding discipline as is the concern over the impact of nanotechnology on human
      environmental health and safety. In this review, we discuss the current state of
      understanding of nanomaterial skin interactions with a specific emphasis on the
      effects of ultraviolet radiation (UVR) skin exposure. Skin is the largest organ
      of the body and is typically exposed to UVR on a daily basis. This necessitates
      the need to understand how UVR skin exposure can influence nanomaterial skin
      penetration, alter nanomaterial systemic trafficking, toxicity, and skin immune
      function. We explore the unique dichotomy that UVR has on inducing both
      deleterious and therapeutic effects in skin. The subject matter covered in this
      review is broadly informative and will raise awareness of potential increased
      risks from nanomaterial skin exposure associated with specific occupational and
      life style choices. The UVR-induced immunosuppressive response in skin raises
      intriguing questions that motivate future research directions in the
      nanotoxicology and nanomedicine fields.

PMID- 24123982
TI  - Historical perspective on developmental concepts and terminology.
AB  - In their ontogeny and phylogeny all living beings are historical entities. The
      revolution in biology of the 18th and 19th centuries that did away with the scala
      naturae according to which we humans, the acme of creation, "made a little lower
      than the angels," also led to the gradual realization that a humble one-celled
      protist ("protoctist"), such as Entamoeba histolytica of ill repute [Margulis and
      Chapman, ] has the same 4-billion-year phylogeny as that of Homo sapiens, vivid
      testimony to common ancestry and the relatedness of all living beings on earth.
      The group of medical geneticists who assembled at the NIH, Bethesda, MD this
      January to address terms pertaining to human ontogeny, did so in the long
      tradition of Sydenham, Linnaeus, Meckel, Geoffroy St-Hilaire pere et fils,
      Wilhelm His and so many others before who had over the previous two centuries
      wrestled as earnestly as they could with concepts of "classification" and
      nomenclature of developmental anomalies. The prior massive need for
      classification per se in medical morphology has diminished over the years in
      favor of ever more sophisticated understanding of pathogenesis and cause through
      experimental biology and genetics; however, in the winter of 2013 it was still
      found prudent to respect terminological precedent on general terms while
      recognizing recent advances in developmental pathology requiring clarification
      and definition of special terms. Efforts along similar lines instigated by the
      German Society of Anatomists at their first meeting in Leipzig in 1887
      culminated, after intense years of work by hundreds of experts and consultants
      under the goad of Wilhelm His, in the Basel Nomina Anatomica [BNA, His (1895)].
      His, himself, stated prefatorily that the BNA had no legislative weight, only an
      evanescent consensus of many to be amended in the future as needed and indicated.
      Without hubris, no one before or after will do the same. The more substantial the
      consensus the more permanent the structure. After some 120 years the BNA is alive
      and flourishing. Now retitled Terminologia Anatomica, it has been amended and
      added to many times, is still in Latin but now with synonyms in English, the new
      lingua franca of science, for every anatomical, histological and embryological
      term. May our successors be equally effective.

PMID- 24123981
TI  - Facial dysostoses: Etiology, pathogenesis and management.
AB  - Approximately 1% of all live births exhibit a minor or major congenital anomaly.
      Of these approximately one-third display craniofacial abnormalities which are a
      significant cause of infant mortality and dramatically affect national health
      care budgets. To date, more than 700 distinct craniofacial syndromes have been
      described and in this review, we discuss the etiology, pathogenesis and
      management of facial dysostoses with a particular emphasis on Treacher Collins,
      Nager and Miller syndromes. As we continue to develop and improve medical and
      surgical care for the management of individual conditions, it is essential at the
      same time to better characterize their etiology and pathogenesis. Here we
      describe recent advances in our understanding of the development of facial
      dysostosis with a view towards early in utero identification and intervention
      which could minimize the manifestation of anomalies prior to birth. The ultimate
      management for any craniofacial anomaly however, would be prevention and we
      discuss this possibility in relation to facial dysostosis.

PMID- 24123983
TI  - Surface-modified functionalized polycaprolactone scaffolds for bone repair: in
      vitro and in vivo experiments.
AB  - A porcine calvaria defect study was carried out to investigate the bone repair
      potential of three-dimensional (3D)-printed poly-epsilon-caprolactone (PCL)
      scaffolds embedded with nanoporous PCL. A microscopic grid network was created by
      rapid prototyping making a 3D-fused deposition model (FDM-PCL). Afterward, the
      FDM-PCL scaffolds were infused with a mixture of PCL, water, and 1,4-dioxane and
      underwent a thermal-induced phase separation (TIPS) followed by lyophilization.
      The TIPS process lead to a nanoporous structure shielded by the printed
      microstructure (NSP-PCL). Sixteen Landrace pigs were divided into two groups with
      8 and 12 weeks follow-up, respectively. A total of six nonpenetrating holes were
      drilled in the calvaria of each animal. The size of the cylindrical defects was h
      10 mm and O 10 mm. The defects were distributed randomly using following groups:
      (a) NSP-PCL scaffold, (b) FDM-PCL scaffold, (c) autograft, (d) empty defect, (a1)
      NSP-PCL scaffold + autologous mononuclear cells, and (a2) NSP-PCL scaffold + bone
      morphogenetic protein 2. Bone volume to total volume was analyzed using
      microcomputed tomography (uCT) and histomorphometry. The uCT and histological
      data showed significantly less bone formation in the NSP-PCL scaffolds in all
      three variations after both 8 and 12 weeks compared to all other groups. The
      positive autograft control had significantly higher new bone formation compared
      to all other groups except the FDM-PCL when analyzed using histomorphometry. The
      NSP-PCL scaffolds were heavily infiltrated with foreign body giant cells
      suggesting an inflammatory response and perhaps active resorption of the scaffold
      material. The unmodified FDM-PCL scaffold showed good osteoconductivity and
      osseointegration after both 8 and 12 weeks.

PMID- 24123984
TI  - Predicting low-pressure O(2) adsorption in nanoporous framework materials for
      sensing applications.
AB  - A set of 98 nanoporous framework material (NFM) structures was investigated by
      classical Grand canonical Monte Carlo simulations for low-pressure O2 adsorption
      properties (Henry's constant and isosteric heat of adsorption). The set of
      materials includes those that have shown high O2 uptake experimentally as well as
      a subset of more than 2000 structures previously screened for noble-gas uptake.
      While use of the general force field UFF is fruitful for noble-gas adsorption
      studies, its use is shown to be limited for the case of O2 adsorption-one
      distinct limitation is a lack of sufficient O2 -metal interactions to be able to
      describe O2 interaction with open metal sites. Nonetheless, those structures
      without open metal sites that have very small pores (<2.5 A) show increased O2
      /N2 selectivity. Additionally, O2 /N2 mixture simulations show that in some
      cases, H2 O or N2 can hinder O2 uptake for NFMs with small pores due to
      competitive adsorption. 

PMID- 24123985
TI  - Finite element methods to analyze helical stent expansion.
AB  - Helical polymeric stents have been proposed as a suitable geometry for
      biodegradable drug-eluting polymer-based stents. However, helical stents often
      experience nonuniform local expansion (dog boning), which can prohibit full stent
      expansion using conventional methods. The development of stents and deployment
      methods is challenging and can be supported by numerical analysis; however, this
      complex problem is often approached with simplified boundary conditions that may
      not be appropriate for helical stents. The finite element method (explicit and
      implicit) was used to investigate three common stent expansion approaches with a
      focus on helical stent geometry, which differs from traditional wire mesh stent
      expansion. Although each of the three methods considered provided some insight
      into the expansion characteristics, common displacement controlled, and uniform
      expansion methods were not able to demonstrate the characteristic local
      deformations observed in expansion. A coupled stent-balloon model, although
      computationally expensive, was able to demonstrate the expected nonuniform
      deformation. To address nonuniform expansion, a progressive expansion approach
      has been investigated and verified numerically. This method may also provide a
      suitable solution for nonuniform expansion in other stent designs by minimizing
      loading and potential damage to the artery that can occur during stent
      deployment.

PMID- 24123986
TI  - Disadvantaged family background and depression among young adults in the United
      States: the roles of chronic stress and self-esteem.
AB  - Although several longitudinal studies have demonstrated that having a
      disadvantaged family background is a risk factor for subsequent symptoms of
      depression, few studies have examined the mediating mechanisms that explain this
      long-term relationship. Thus, this study uses US national longitudinal data and
      integrates social stress theory with the life course perspective by focusing on
      two mediating mechanisms-the chronic stress of poverty and self-esteem during the
      transition to adulthood. Results reveal that self-esteem largely mediates the
      inverse relationship between parental education and levels of depressive symptoms
      in young adulthood. However, the inverse relationship between parental
      occupational prestige and depressive symptoms among young adults is not mediated
      by self-esteem, but rather long durations of poverty across 16 years. Overall,
      these findings suggest that different components of family socioeconomic status
      can leave a lasting imprint on mental health via the self-concept and the chronic
      stress of poverty throughout the journey to adulthood.

PMID- 24123987
TI  - Dinner rituals that correlate with child and adult BMI.
AB  - OBJECTIVE: What predicts whether a child will be at risk for obesity? Whereas
      past research has focused on foods, eating habits, feeding styles, and family
      meal patterns, this study departs from a food-centric approach to examine how
      various dinner rituals might influence the BMIs of children and adults. METHODS:
      In this study of 190 parents (BMI = 29.1 +/- 7.2) and 148 children (BMI = 20.3 +/
      4.4), the relationship between their BMIs and everyday family dinner rituals was
      examined using both correlation and regression analysis (controlled for
      educational level of parents). RESULTS: Families who frequently ate dinner in the
      kitchen or dining room had significantly lower BMIs for both adults (r = -0.31)
      and children (r = -0.24) compared to families who ate elsewhere. Additionally,
      helping cook dinner was associated with higher BMI for girls (r = 0.26), and
      remaining at the table until everyone is finished with eating was associated with
      lower BMI for boys (r = -0.31). CONCLUSIONS: Dinner tables may be one place where
      social support and family involvement meet-both of which relate to the BMI of
      children as well as parents. Family meals and their rituals might be an
      underappreciated battleground to fight obesity.

PMID- 24123989
TI  - Bacterial microbiome of Coptotermes curvignathus (Isoptera: Rhinotermitidae)
      reflects the coevolution of species and dietary pattern.
AB  - Coptotermes curvignathus Holmgren is capable of feeding on living trees. This
      ability is attributed to their effective digestive system that is furnished by
      the termite's own cellulolytic enzymes and cooperative enzymes produced by their
      gut microbes. In this study, the identity of an array of diverse microbes
      residing in the gut of C. curvignathus was revealed by sequencing the near-full
      length 16S rRNA genes. A total of 154 bacterial phylotypes were found. The
      Bacteroidetes was the most abundant phylum and accounted for about 65% of the gut
      microbial profile. This is followed by Firmicutes, Actinobacteria, Spirochetes,
      Proteobacteria, TM7, Deferribacteres, Planctomycetes, Verrucomicrobia, and
      Termite Group 1. Based on the phylogenetic study, this symbiosis can be a result
      of long coevolution of gut enterotypes with the phylogenic distribution, strong
      selection pressure in the gut, and other speculative pressures that determine
      bacterial biome to follow. The phylogenetic distribution of cloned rRNA genes in
      the bacterial domain that was considerably different from other termite reflects
      the strong selection pressures in the gut where a proportional composition of gut
      microbiome of C. curvignathus has established. The selection pressures could be
      linked to the unique diet preference of C. curvignathus that profoundly feeds on
      living trees. The delicate gut microbiome composition may provide available
      nutrients to the host as well as potential protection against opportunistic
      pathogen.

PMID- 24123991
TI  - Shaping nanostructures for applications in energy conversion and storage.

PMID- 24123988
TI  - Understanding the basis of auriculocondylar syndrome: Insights from human, mouse
      and zebrafish genetic studies.
AB  - Among human birth defect syndromes, malformations affecting the face are perhaps
      the most striking due to cultural and psychological expectations of facial shape.
      One such syndrome is auriculocondylar syndrome (ACS), in which patients present
      with defects in ear and mandible development. Affected structures arise from
      cranial neural crest cells, a population of cells in the embryo that reside in
      the pharyngeal arches and give rise to most of the bone, cartilage and connective
      tissue of the face. Recent studies have found that most cases of ACS arise from
      defects in signaling molecules associated with the endothelin signaling pathway.
      Disruption of this signaling pathway in both mouse and zebrafish results in loss
      of identity of neural crest cells of the mandibular portion of the first
      pharyngeal arch and the subsequent repatterning of these cells, leading to
      homeosis of lower jaw structures into more maxillary-like structures. These
      findings illustrate the importance of endothelin signaling in normal human
      craniofacial development and illustrate how clinical and basic science approaches
      can coalesce to improve our understanding of the genetic basis of human birth
      defect syndromes. Further, understanding the genetic basis for ACS that lies
      outside of known endothelin signaling components may help elucidate unknown
      aspects critical to the establishment of neural crest cell patterning during
      facial morphogenesis.

PMID- 24123994
TI  - The sensory innervation of the human pharynx: searching for mechanoreceptors.
AB  - The coordinate neural regulation of the upper airways muscles is basic to control
      airway size and resistance. The superior constrictor pharyngeal muscle (SCPM)
      forms the main part of the lateral and posterior walls of the pharynx and
      typically is devoid of muscle spindles, the main type of proprioceptor. Because
      proprioception arising from SCPM is potentially important in the physiology of
      the upper airways, we have investigated if there are mechanical sensory nerve
      endings substitute for the muscle spindles. Samples of human pharynx were
      analyzed using immunohistochemistry associated to general axonic and Schwann
      cells markers (NSE, PGP 9.5, RT-97, and S100P), intrafusal muscle fiber markers,
      and putative mechanical sense proteins (TRPV4 and ASIC2). Different kinds of
      sensory corpuscles were observed in the pharynx walls (Pacini-like corpuscles,
      Ruffini-like corpuscles, spiral-wharves nerve structures, and others) which are
      supplied by sensory nerves and express putative mechanoproteins. No evidence of
      muscle spindles was observed. The present results demonstrate the occurrence of
      numerous and different morphotypes of sensory corpuscles/mechanoreceptors in
      human pharynx that presumably detect mechanical changes in the upper airways and
      replace muscle spindles for proprioception. Present findings are of potential
      interest for the knowledge of pathologies of the upper airways with supposed
      sensory pathogenesis.

PMID- 24123995
TI  - Parylene mobile microplates integrated with an enzymatic release for handling of
      single adherent cells.
AB  - An approach for manipulating single adherent cells is developed that is
      integrated with an enzymatic batch release. This strategy uses an array of
      releasable microfabricated mobile substrates, termed microplates, formed from a
      biocompatible polymer, parylene. A parylene microplate array of 10-70 MUm in
      diameter can be formed on an alginate hydrogel sacrificial layer by using a
      standard photolithographic process. The parylene surfaces are modified with
      fibronectin to enhance cell attachment, growth, and stretching. To load single
      cells onto these microplates, cells are initially placed in suspension at an
      optimized seeding density and are allowed to settle, stretch, and grow on
      individual microplates. The sacrificial layer underneath the microplate array can
      be dissolved on a time-scale of several seconds without cytotoxicity. This system
      allows the inspection of selected single adherent cells. The ability to assess
      single cells while maintaining their adhesive properties will broaden the
      examination of a variety of attributes, such as cell shape and cytoskeletal
      properties. 

PMID- 24123996
TI  - Hemodialysis clearance of iosimenol, a novel iso-osmolar radiographic contrast
      medium.
AB  - BACKGROUND: Iodinated contrast media (CM) have molecular and pharmacokinetic
      properties likely to make them highly dialyzable. Controlled clinical studies
      allowing for comparisons of hemodialysis clearance between different test
      substances and in multiple hemodialysis filters are, however, complex and not
      always practically feasible. A miniaturized in vitro method was therefore
      developed to evaluate the dialyzability of a new CM. PURPOSE: To evaluate
      hemodialysis clearance of iosimenol, a novel iso-osmolar contrast medium (CM), in
      a select variety of hemodialysis filters and in comparison to commercially
      available CM. MATERIAL AND METHODS: Three different high-flux and one low-flux
      membrane were used in miniaturized dialyzers to evaluate the in vitro blood
      clearance of iosimenol. Commercially available CM (iodixanol and iohexol) served
      as control substances. In vitro dialysis parameters were then used to predict
      clinical hemodialysis clearances. Residual ratios of endogenous substances
      (inorganic phosphate, urea nitrogen, creatinine, total bilirubin, and albumin)
      were used as proof of reliability of the in vitro dialysis system. RESULTS:
      Dialyzable small endogenous molecules were readily eliminated in all membranes.
      The removal ratios of iosimenol were generally similar to that of iodixanol in
      all membranes except the high-flux polysulfone but were consistently lower than
      that of iohexol. The blood clearance of iosimenol during clinical hemodialysis
      was predicted as, on average, approximately 85 mL/min with the high-flux
      membranes and 47 mL/min with the low-flux membrane. CONCLUSION: The dialyzability
      of iosimenol was evaluated using a newly developed in vitro dialysis system, and
      iosimenol was readily cleared from blood with all four tested membranes. And it
      is suggested that the dialysis parameters can predict clinical hemodialysis
      clearance of CM.

PMID- 24123997
TI  - Synthesis of some novel quinone diimine derivatives of benzo-15-crown-5 for
      application in Hg(2+) recognition.
AB  - A series of novel fluoroionophore bearing derivatives of benzo-15-crown-5 were
      synthesized by the amination of benzo-15-crown-5 followed by condensation with
      different quinones in the presence of titanium tetrachloride (TiCl4 ) and 1,4
      diazabicyclo-[2.2.2]octane. The compounds were characterized by infrared, (1) H
      and (13) C nuclear magnetic resonance, mass spectroscopy and elemental analysis.
      Absorption and fluorescence spectral characteristics of these compounds were
      studied. It was observed that the anthraquinone derivative was acting as an
      Hg(2+) ion sensor.

PMID- 24123998
TI  - The stimulatory effect of mannitol on levan biosynthesis: Lessons from metabolic
      systems analysis of Halomonas smyrnensis AAD6(T.).
AB  - Halomonas smyrnensis AAD(T) is a halophilic, gram-negative bacterium that can
      efficiently produce levan from sucrose as carbon source via levansucrase
      activity. However, systems-based approaches are required to further enhance its
      metabolic performance for industrial application. As an important step toward
      this goal, the genome-scale metabolic network of Chromohalobacter salexigens
      DSM3043, which is considered a model organism for halophilic bacteria, has been
      reconstructed based on its genome annotation, physiological information, and
      biochemical information. In the present work, the genome-scale metabolic network
      of C. salexigens was recruited, and refined via integration of the available
      biochemical, physiological, and phenotypic features of H. smyrnensis AAD6(T) .
      The generic metabolic model, which comprises 1,393 metabolites and 1,108
      reactions, was then systematically analyzed in silico using constraints-based
      simulations. To elucidate the relationship between levan biosynthesis and other
      metabolic processes, an enzyme-graph representation of the metabolic network and
      a graph decomposition technique were employed. Using the concept of control
      effective fluxes, significant links between several metabolic processes and levan
      biosynthesis were estimated. The major finding was the elucidation of the
      stimulatory effect of mannitol on levan biosynthesis, which was further verified
      experimentally via supplementation of mannitol to the fermentation medium. The
      optimal concentration of 30 g/L mannitol supplemented to the 50 g/L sucrose-based
      medium resulted in a twofold increase in levan production in parallel with
      increased sucrose hydrolysis rate, accumulated extracellular glucose, and
      decreased fructose uptake rate.

PMID- 24123999
TI  - Tailoring of antibacterial Ag nanostructures on TiO2 nanotube layers by magnetron
      sputtering.
AB  - To reduce the incidence of postsurgical bacterial infection that may cause
      implantation failure at the implant-bone interface, surface treatment of titanium
      implants with antibiotic materials such as silver (Ag) has been proposed. The
      purpose of this work was to create TiO2 nanotubes using plasma electrolytic
      oxidation (PEO), followed by formation of an antibacterial Ag nanostructure
      coating on the TiO2 nanotube layer using a magnetron sputtering system. PEO was
      performed on commercially pure Ti sheets. The Ag nanostructure was added onto the
      resulting TiO2 nanotube using magnetron sputtering at varying deposition rates.
      Field emission scanning electron microscopy and transmission electron microscopy
      were used to characterize the surface, and Ag content on the TiO2 nanotube layer
      was analyzed by X-ray diffraction and X-ray photoelectron spectroscopy. Scanning
      probe microscopy for surface roughness and contact angle measurement were used to
      indirectly confirm enhanced TiO2 nanotube hydrophilicity. Antibacterial activity
      of Ag ions in solution was determined by inductively coupled plasma mass
      spectrometry and antibacterial testing against Staphylococcus aureus (S. aureus).
      In vitro, TiO2 nanotubes coated with sputtered Ag resulted in significantly
      reduced S. aureus. Cell viability assays showed no toxicity for the lowest
      sputtering time group in the osteoblastic cell line MC3T3-E1. These results
      suggest that a multinanostructured layer with a biocompatible TiO2 nanotube and
      antimicrobial Ag coating is a promising biomaterial that can be tailored with
      magnetron sputtering for optimal performance.

PMID- 24124000
TI  - Elements of morphology: general terms for congenital anomalies.
AB  - An international group of clinicians working in the field of dysmorphology has
      established a process for the standardization of terms used to describe human
      morphology. The goals are to standardize these terms and develop consensus
      regarding their definitions. This project will increase the usefulness and
      precision of descriptions of the human phenotype and facilitate reliable
      comparisons of phenotypic findings among clinicians and researchers in medicine,
      developmental biology, and genetics. Here we define and illustrate the general
      terms that describe congenital anomalies as related to human conditions.

PMID- 24124001
TI  - TGFBR3 co-downregulated with GATA3 is associated with methylation of the GATA3
      gene in bladder urothelial carcinoma.
AB  - Bladder urothelial carcinoma (BUC) accounts for ~90% of all cases of bladder
      cancer. Reduced expression of TGFBR3 has been frequently observed in several
      types of human cancers. However, little is known about whether expression of
      TGFBR3 reduced in BUC and the underlying mechanisms. In the present study, we
      performed quantitative real-time PCR to examine the mRNA expression of TGFBR3 and
      GATA3, and bisulfite genomic sequencing to evaluate the methylation status in
      TGFBR3 and GATA3 promoter regions in fresh tumor and the corresponding
      paracarcinoma tissues from 29 patients with BUC. As a result, the expression of
      TGFBR3 and GATA3, a transcriptional factor of the TGFBR3 gene, were found to be
      co-downregulated in BUC. Moreover, our findings indicated that GATA3 promoter
      methylation was one of the reasons for silencing of GATA3 and TGFBR3 in BUC,
      albeit TGFBR3 methylation and mutation were not associated with reduced
      expression of TGFBR3 mRNA in BUC. In summary, our findings suggest that
      methylation in the GATA3 promoter region may inhibit the expression of GATA3
      mRNA, which leads to the reduced expression of TGFBR3 mRNA in BUC.

PMID- 24124002
TI  - The Japanese ladybirds, Coccinula crotchi and Coccinula sinensis, are infected
      with very closely related strains of male-killing Flavobacterium.
AB  - Male-killing is 1 of 4 known strategies that inherited parasitic endosymbionts
      have evolved to manipulate their host's reproduction. In early male-killing,
      infected male offspring are killed early in embryogenesis. Within the Insecta,
      male-killing bacteria have been found in a wide range of hosts. The Coccinellidae
      families of beetles, better known as ladybirds, are particularly prone to male
      killer invasion. In samples of the coccinellid, Coccinula crotchi, from Japan, a
      new male-killing bacterium was revealed by phenotypic assay. Molecular genetic
      analysis revealed the identity to be a tetracycline-sensitive Flavobacterium that
      causes female-biased offspring sex ratio. Furthermore, that Flavobacterium strain
      was found to be closely related to the Flavobacterium causing male-killing in the
      congeneric Japanese coccinellid, Coccinula sinensis, which was collected from the
      same region. However, we found slightly different Flavobacterium strains
      infecting C. sinensis from regions with different environmental conditions. This
      may be an indication of horizontal transmission of male-killing Flavobacterium
      between these 2 ladybird spices. Finally, environmental conditions may affect the
      spread of male-killing bacteria among their hosts.

PMID- 24124003
TI  - Effect of UV-irradiation intensity on graft polymerization of 2
      methacryloyloxyethyl phosphorylcholine on orthopedic bearing substrate.
AB  - Photoinduced grafting of 2-methacryloyloxyethyl phosphorylcholine (MPC) onto
      cross-linked polyethylene (CLPE) was investigated for its ability to reduce the
      wear of orthopedic bearings. We investigated the effect of UV-irradiation
      intensity on the extent of poly(MPC) (PMPC) grafting, and found that it increased
      with increasing intensity up to 7.5 mW/cm(2), and the remained fairly constant.
      It was found to be extremely important to carefully control the UV intensity, as
      at higher values, a PMPC gel formed via homopolymerization of the MPC, resulting
      in the formation of cracks at the interface of the PMPC layer and the CLPE
      substrate. When the CLPE was exposed to UV-irradiation during the graft
      polymerization process, some of its physical and mechanical properties were
      slightly changed due to cross-linking and scission effects in the surface region;
      however, the results of all of the tests exceed the lower limits of the ASTM
      standards. Modification of the CLPE surface with the hydrophilic PMPC layer
      increased lubrication to levels that match articular cartilage. The highly
      hydrated thin PMPC films mimicked the native cartilage extracellular matrix that
      covers synovial joint surface, acting as an extremely efficient lubricant, and
      providing high-wear resistance.

PMID- 24124004
TI  - Photoluminescence in K3 Ca2 (SO4 )3 Cl-doped Eu(3+) phosphor.
AB  - In this article we report Eu(3+) luminescence in novel K3 Ca2 (SO4 )3 Cl
      phosphors prepared by wet chemical methods. The Eu(3+) emission was observed at
      594 nm and 615 nm, keeping the excitation wavelength constant at 396 nm nearer to
      light-emitting diode excitation, Furthermore, phosphors were characterized by X
      ray diffraction for the confirmation of crystallinity. The variation of the
      photoluminescence intensity with impurity concentration has also been discussed.
      Thus, prominent emission in the red region makes prepared phosphors more
      applicable for white light-emitting diodes.

PMID- 24124005
TI  - The effects of membrane filters used in biopharmaceutical processes on the
      concentration and composition of polysorbate 20.
AB  - Polysorbate 20 (PS-20) is often included in the formulation for therapeutic
      proteins to reduce protein aggregation and surface adsorption. During the
      production process of therapeutic proteins, various membrane filters are used to
      filter product pools containing PS-20. The purpose of this study is to quantify
      the effects of these membrane filtration processes on the concentration and
      composition of PS-20. A quantitative understanding of this process provides the
      knowledge base for better controlling the consistency of formulation excipients
      in drug products. PS-20 solutions (without protein) were filtered through either
      0.2 um sterilizing filters or membrane filters with 30 kDa MWCO. The
      concentration of PS-20 was measured by a mixed-mode chromatography method and a
      nuclear magnetic resonance spectroscopy (NMR) assay. The composition of PS-20 was
      characterized by (1) H-NMR and a reverse-phase chromatography method. Non
      specific adsorption of PS-20 on both the sterilizing filter and 30 kDa MWCO
      membrane filter was quantified. Composition of PS-20 was altered after 30 kDa
      MWCO membrane filtration, possibly because the different interactions between
      heterogeneous PS-20 components and the 30 kDa MWCO membrane were not uniform. As
      a result, the retentate after the 30 kDa MWCO membrane filtration step contains
      no POE sorbitan and increased amount of POE sorbitan di-esters and tri-esters.

PMID- 24124006
TI  - Biallelic SEMA3A defects cause a novel type of syndromic short stature.
AB  - Chromosomal microarray testing is commonly used to identify disease causing de
      novo copy number variants in patients with developmental delay and multiple
      congenital anomalies. In such a patient we now observed an 150 kb deletion on
      chromosome 7q21.11 affecting the first exon of the axon guidance molecule gene
      SEMA3A (sema domain, immunoglobulin domain (Ig), short basic domain, secreted,
      (semaphorin) 3A). This deletion was inherited from the healthy father, but
      considering the function of SEMA3A and phenotypic similarity to the knock-out
      mice, we still assumed a pathogenic relevance and tested for a recessive second
      defect. Sequencing of SEMA3A in the patient indeed revealed the de novo in-frame
      mutation p.Phe316_Lys317delinsThrSerSerAsnGlu. Cloning of the mutated allele in
      combination with two informative SNPs confirmed compound heterozygosity in the
      patient. While the altered protein structure was predicted to be benign, aberrant
      splicing resulting in a premature stop codon was proven by RT-PCR to occur in
      about half of the transcripts from this allele. Expression profiling in human
      fetal and adult cDNA panels, confirmed a high expression of SEMA3A in all brain
      regions as well as in adult and fetal heart and fetal skeletal muscle. Normal
      intellectual development in the patient was surprising but may be explained by
      the remaining 20% of SEMA3A expression level demonstrated by quantitative RT-PCR.
      We therefore report a novel autosomal recessive syndrome characterized by
      postnatal short stature with relative macrocephaly, camptodactyly, septal heart
      defect and several minor anomalies caused by biallelic mutations in SEMA3A.

PMID- 24124007
TI  - Designing colon-specific delivery systems for anticancer drug-loaded
      nanoparticles: an evaluation of alginate carriers.
AB  - Incorporation of drug-loaded nanoparticles (NPs) in colon-specific delivery
      systems shows potential for raising local drug concentrations, tumor targeting
      and improving chemotherapy. Alginate microcapsules (15-80 um diameter) containing
      insoluble Eudragit((r)) RS NPs as models were characterized precisely in terms of
      NP loading and release kinetics. High NP loading (22%, w/w of the dried
      microcapsules) combined with negligible release in simulated gastric fluid (SGF)
      and simulated intestinal fluid (SIF) suggested that high concentrations of NPs
      could be transported to the colon. However, NP aggregation was confirmed at
      extremely low concentration (0.0003%, w/v) in alginate solution (0.007%, w/v) and
      after release from alginate microcapsules. Indomethacin, a model anticolorectal
      cancer drug, was encapsulated in pH-responsive Eudragit((r)) S100 NPs (116 nm,
      5%, w/w drug loading) using the nanoprecipitation method. Approximately 90% of
      the drug load was released from the NPs in SGF and SIF before transfer to
      simulated colon fluid (SCF). However, incorporation of NPs in 2 mm alginate
      pellets resulted in a significantly higher fraction of the drug load (around 60%)
      being available for release in SCF. Delivery of isolated NPs to the colon for
      interaction with and uptake by cancer cells requires elimination of NP-excipient
      interactions that promote NP aggregation. NP-loaded alginate carriers, meanwhile,
      offer a promising strategy for delivery of anticancer drugs to tumor sites in the
      colon and reducing systemic side effects.

PMID- 24124008
TI  - Hyaluronic acid colloidal gels as self-assembling elastic biomaterials.
AB  - Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a
      variety of applications in medicine. The use of HA as a filler or scaffold for
      regenerating tissues often requires improving the elastic properties of HA. This
      is conventionally accomplished via chemical crosslinking, which might require the
      generation of toxic free radicals. Although the mechanical properties of the
      resulting gel material can be tuned, these types of materials are static and
      susceptible to mechanical failure. The aim of this study was to develop a
      colloidal system for scaffold fabrication that is held together by physical
      interactions between HA nanoparticles. HA nanoparticles composed of 17 kDa HA
      suspended in water at different concentrations (15%, 30%, and 45% w/v,
      respectively) formed a stable three-dimensional (3D) colloidal gel as a result of
      physical entanglement of free polymer chains on the surfaces of nanoparticles.
      The swelling ratio, shear moduli (G), compressive failure properties, and
      viscosity of colloidal gels were concentration dependent. The colloidal gels also
      were found to exhibit dynamic and recoverable properties, thus suggesting that
      these "self-associating colloids" offer characteristics distinct arising from
      crosslinked polymers or high concentration colloids.

PMID- 24124009
TI  - Oxidative methane reforming with an intelligent catalyst: sintering-tolerant
      supported nickel nanoparticles.
AB  - Smart Catalyst: The cyclical diffusion of nanometer-sized nickel clusters into
      and out of the perovskite structure under elevated temperature and reducing and
      oxidizing atmosphere could in situ redeliver and redisperse Ni, thereby
      reinforcing the anti-coking and -sintering of Ni during oxidative reforming of
      CH4 . 

PMID- 24124010
TI  - The ontology of craniofacial development and malformation for translational
      craniofacial research.
AB  - We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as
      a mechanism for representing knowledge about craniofacial development and
      malformation, and for using that knowledge to facilitate integrating craniofacial
      data obtained via multiple techniques from multiple labs and at multiple levels
      of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium,
      whose goal is to promote and enable research into the genetic and epigenetic
      causes of specific craniofacial abnormalities through the provision of publicly
      accessible, integrated craniofacial data. However, the OCDM should be usable for
      integrating any web-accessible craniofacial data, not just those data available
      through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA),
      our comprehensive ontology of canonical human adult anatomy, and includes modules
      to represent adult and developmental craniofacial anatomy in both human and
      mouse, mappings between homologous structures in human and mouse, and associated
      malformations. We describe these modules, as well as prototype uses of the OCDM
      for integrating craniofacial data. By using the terms from the OCDM to annotate
      data, and by combining queries over the ontology with those over annotated data,
      it becomes possible to create "intelligent" queries that can, for example, find
      gene expression data obtained from mouse structures that are precursors to
      homologous human structures involved in malformations such as cleft lip. We
      suggest that the OCDM can be useful not only for integrating craniofacial data,
      but also for expressing new knowledge gained from analyzing the integrated data.

PMID- 24124012
TI  - Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota
      and glycemia in obese rats.
AB  - OBJECTIVE: Prebiotics and probiotics may be able to modify an obesity-associated
      gut microbiota. The aim of this study was to examine the individual and combined
      effects of the prebiotic oligofructose (OFS) and the probiotic Bifidobacterium
      animalis subsp. lactis BB-12 (BB-12) on gut microbiota and host metabolism in
      obese rats. METHODS: Adult male, diet-induced obese Sprague Dawley rats were
      randomized to: (1) Control (C); (2) 10% OFS; (3) BB-12; (4) OFS + BB-12 for 8
      weeks (n = 9-10 rats/group). Body composition, glycemia, gut permeability,
      satiety hormones, cytokines, and gut microbiota were examined. RESULTS:
      Prebiotic, but not probiotic reduced energy intake, weight gain, and fat mass (P
      < 0.01). OFS, BB-12, and the combined OFS + BB-12 improved glycemia (P < 0.05).
      Individually, OFS and BB-12 reduced insulin levels (P < 0.05). Portal GLP-1 was
      increased with OFS, whereas probiotic increased GLP-2 (P < 0.05). There was a
      marked increase in bifidobacteria and lactobacilli (P < 0.01) with OFS that was
      not observed with probiotic alone. CONCLUSIONS: The impact of prebiotic intake on
      body composition and gut microbiota was of greater magnitude than the probiotic
      BB-12. Despite this, an improvement in glucose AUC with both prebiotic or
      probiotic demonstrates the beneficial role of each of these "biotic" agents in
      glycemic control.

PMID- 24124011
TI  - Quality of care for incident lupus nephritis among Medicaid beneficiaries in the
      United States.
AB  - OBJECTIVE: We investigated the quality of care and factors associated with
      variations in care among a national cohort of Medicaid enrollees with incident
      lupus nephritis. METHODS: Using Medicaid Analytic eXtract files from 47 US states
      and the District of Columbia for 2000-2006, we identified a cohort of individuals
      with incident lupus nephritis. We assessed performance on 3 measures of health
      care quality: receipt of immunosuppressive, renal-protective antihypertensive,
      and antimalarial medications. We examined performance on these measures over 1
      year and applied multivariable logistic regression models to understand whether
      sociodemographic, geographic, or health care access factors were associated with
      higher performance on quality measures. RESULTS: We identified 1,711 Medicaid
      enrollees with incident lupus nephritis. Performance on quality measures was low
      at 90 days (21.9% for immunosuppressive therapy, 44.0% for renal protection, and
      36.4% for antimalarials) but increased by 1 year (33.7%, 56.4%, and 45.8%,
      respectively). Younger individuals, African Americans, and Hispanics were more
      likely to receive immunosuppressive therapy and hydroxychloroquine. Younger
      individuals were less likely to receive renal-protective antihypertensive
      medications. We found significant geographic variation in performance, with
      patients in the Northeast receiving higher quality of care compared to other
      regions. Poor access to health care, as assessed by having a greater number of
      treat-and-release emergency department visits compared to ambulatory encounters,
      was associated with lower receipt of recommended treatment. CONCLUSION: These
      nationwide data suggest low overall quality of care and potential delays in care
      for Medicaid enrollees with incident lupus nephritis. Significant regional
      differences also suggest room for quality improvement.

PMID- 24124013
TI  - The expression analysis of silk gland-enriched intermediate-size non-coding RNAs
      in silkworm Bombyx mori.
AB  - Small non-protein coding RNAs (ncRNAs) play important roles in development,
      stress response and other cellular processes. Silkworm is an important model for
      studies on insect genetics and control of Lepidopterous pests. We have previously
      identified 189 novel intermediate-size ncRNAs in silkworm Bombyx mori, including
      40 ncRNAs that showed altered expression in different developmental stages. Here
      we characterized the functions of these 40 ncRNAs by measuring their expressions
      in six tissues of the fifth instar larvae using Northern blot and real-time
      polymerase chain reaction assays. We identified nine ncRNAs (four small nucleolar
      RNAs and five unclassified ncRNAs) that were enriched in silk gland, including
      four ncRNAs that showed silk gland-specific expression. We further showed that
      three of nine silk gland-enriched ncRNAs were predominantly expressed in the
      anterior silk gland, whereas another three ncRNAs were highly accumulated in the
      posterior silk gland, suggesting that they may play different roles in fibroin
      synthesis. Furthermore, an unclassified ncRNA, Bm-152, exhibited converse
      expression pattern with its antisense host gene gartenzwerg in diverse tissues,
      and might regulate the expression of gartenzwerg through RNA-protein complex. In
      addition, two silk gland-enriched ncRNAs Bm-102 and Bm-159 can be found in
      histone modification complex, which indicated that they might play roles through
      epigenetic modifications. Taken together, we provided the first expression and
      preliminary functional analysis of silk gland-enriched ncRNAs, which will help
      understand the molecular mechanism of silk gland-development and fibroin
      synthesis. 

PMID- 24124014
TI  - Distinct types of lipofuscin pigment in the hippocampus and cerebellum of aged
      cheirogaleid primates.
AB  - The formation of autofluorescent lipopigment or lipofuscin is a highly consistent
      and reliable cytological change that correlates with cellular aging in
      postmitotic cells. One causal factor of lipofuscinogenesis involves free radical
      induced lipid peroxidation. In mammals, dentate gyrus neurons and Purkinje cells
      are usually affected widely. In this study, we investigated the ultrastructure of
      lipofuscin deposits in large neurons of the dentate gyrus and in Purkinje cells
      of aged fat-tailed dwarf lemurs (Cheirogaleus medius Geoffroy, 1812) with
      electron and confocal microscopy and compared it with previous observations in
      other species. Cheirogaleid primates such as mouse and dwarf lemurs are archaic
      primates that provide interesting nonhuman models of aging. Our study revealed
      region-specific as well as species-specific characteristics of lipofuscin
      ultrastructure. This suggests differences in cellular metabolism and/or in
      organelles involved in lipofuscin production in cerebellar Purkinje cells and in
      hippocampal dentate gyrus neurons.

PMID- 24124016
TI  - Drug-facilitated sexual crime by use of ketamine and diazepam by a gynaecologist.

PMID- 24124015
TI  - The centrality of RNA for engineering gene expression.
AB  - Synthetic biology holds promise as both a framework for rationally engineering
      biological systems and a way to revolutionize how we fundamentally understand
      them. Essential to realizing this promise is the development of strategies and
      tools to reliably and predictably control and characterize sophisticated patterns
      of gene expression. Here we review the role that RNA can play towards this goal
      and make a case for why this versatile, designable, and increasingly
      characterizable molecule is one of the most powerful substrates for engineering
      gene expression at our disposal. We discuss current natural and synthetic RNA
      regulators of gene expression acting at key points of control--transcription,
      mRNA degradation, and translation. We also consider RNA structural probing and
      computational RNA structure predication tools as a way to study RNA structure and
      ultimately function. Finally, we discuss how next-generation sequencing methods
      are being applied to the study of RNA and to the characterization of RNA's many
      properties throughout the cell.

PMID- 24124017
TI  - Engineering stem cell fate with biochemical and biomechanical properties of
      microcarriers.
AB  - Microcarriers have been widely used for various biotechnology applications
      because of their high scale-up potential, high reproducibility in regulating
      cellular behavior, and well-documented compliance with current Good Manufacturing
      Practices (cGMP). Recently, microcarriers have been emerging as a novel approach
      for stem cell expansion and differentiation, enabling potential scale-up of stem
      cell-derived products in large bioreactors. This review summarizes recent
      advances of using microcarriers in mesenchymal stem cell (MSC) and pluripotent
      stem cell (PSC) cultures. From the reported data, efficient expansion and
      differentiation of stem cells on microcarriers rely on their ability to modulate
      cell shape (i.e. round or spreading) and cell organization (i.e. aggregate size).
      Nonetheless, current screening of microcarriers remains empirical, and accurate
      understanding of how stem cells interact with microcarriers still remains
      unknown. This review suggests that accurate characterization of biochemical and
      biomechanical properties of microcarriers is required to fully exploit their
      potential in regulating stem cell fate decision. Due to the variety of
      microcarriers, such detailed analyses should lead to the rational design of
      application-specific microcarriers, enabling the exploitation of reproducible
      effects for large scale biomedical applications.

PMID- 24124018
TI  - The reciprocal relationship between work characteristics and employee burnout and
      engagement: a longitudinal study of firefighters.
AB  - The paradigm of this study is positive occupational psychology, with the job
      demands-resources model as the research model and the Conservation of Resources
      theory as the general stress theory. The research design analyses the job demands
      resources model's dynamic nature with normal and reversed causation effects
      between work characteristics and psychological well-being among Portuguese
      firefighters. In addition, we analyse a positive (engagement) dimension and a
      negative (burnout) dimension in the firefighters' well-being, because previously,
      studies have merely focused on the strain or stress of these professionals. The
      research questionnaire was distributed to a sample of 651 firefighters, and a two
      wave full panel design was used. Cross-lagged panel analyses indicated that the
      causal direction of the relationship between organizational demands and burnout
      is reciprocal. Also, we found that the reciprocal model, including cross-lagged
      reciprocal relationships between organizational demands/supervisory support and
      burnout/engagement, respectively, is what fits the data best. Practical
      implications to develop organizational change programmes and suggestions for
      future research regarding the promotion of occupational health are discussed.

PMID- 24124019
TI  - Solving the puzzle of spinal muscular atrophy: what are the missing pieces?
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive, lower motor neuron
      disease. Clinical heterogeneity is pervasive: three infantile (type I-III) and
      one adult-onset (type IV) forms are recognized. Type I SMA is the most common
      genetic cause of death in infancy and accounts for about 50% of all patients with
      SMA. Most forms of SMA are caused by mutations of the survival motor neuron
      (SMN1) gene. A second gene that is 99% identical to SMN1 (SMN2) is located in the
      same region. The only functionally relevant difference between the two genes
      identified to date is a C -> T transition in exon 7 of SMN2, which determines an
      alternative spliced isoform that predominantly excludes exon 7. Thus, SMN2 genes
      do not produce sufficient full length SMN protein to prevent the onset of the
      disease. Since the identification of the causative mutation, biomedical research
      of SMA has progressed by leaps and bounds: from clues on the function of SMN
      protein, to the development of different models of the disease, to the
      identification of potential treatments, some of which are currently in human
      trials. The aim of this review is to elucidate the current state of knowledge,
      emphasizing how close we are to the solution of the puzzle that is SMA, and, more
      importantly, to highlight the missing pieces of this puzzle. Filling in these
      gaps in our knowledge will likely accelerate the development and delivery of
      efficient treatments for SMA patients and be a prerequisite towards achieving our
      final goal, the cure of SMA.

PMID- 24124020
TI  - Selection and characterisation of an HD1-like Bacillus thuringiensis isolate with
      a high insecticidal activity against Spodoptera littoralis (Lepidoptera:
      Noctuidae).
AB  - BACKGROUND: Spodoptera littoralis (Boisduval) larvae are known by their
      susceptibility to Bacillus thuringiensis subsp. aizawai strains. In order to
      prevent the appearance of B. thuringiensis (Bt) resistance and to develop
      economical Bt-based biopesticides, the selection and the characterisation of a B.
      thuringiensis isolate toxic against S. littoralis larvae and overproducing delta
      endotoxins were investigated. RESULTS: Among 124 Tunisian B. thuringiensis
      isolates assessed against S. littoralis larvae, four isolates showed toxicity
      similar to and higher than the toxicity of the aizawai strain HD133 and the
      kurstaki strain HD1 respectively. The plasmid pattern of the selected isolates
      was similar to that of HD1. Polymerase chain reaction (PCR) analysis using
      specific primers revealed that these isolates present different gene contents.
      The only detected gene encoding Spodoptera-specific toxin was cry9. The selected
      isolates were found to produce bipyramidal and cubic crystals. The assessment of
      delta-endotoxin production by these isolates showed that BUPM28 produced 43.71
      and 80.81% more delta-endotoxin than HD1 and HD133 respectively. The application
      of osmotic or heat shock stress on the BUPM28 isolate made it possible to enhance
      delta-endotoxin production by 22 and 23% respectively. CONCLUSION: On the basis
      of its potent insecticidal activity and its high level of delta-endotoxin
      production, the BUPM28 isolate can be considered to be an effective alternative
      for the control of S. littoralis.

PMID- 24124021
TI  - Is keratinized mucosa indispensable to maintain peri-implant health? A systematic
      review of the literature.
AB  - The significance of keratinized mucosa (KM) around dental implants is still not
      well explained and has been controversial. The aim of this systematic review was
      to evaluate the importance of KM around dental implants. The electronic databases
      Cochrane library, MEDLINE, EMBASE, and Virtual Health Library (VHL) databases
      were utilized to search original articles from 2006 to March 2013. The inclusion
      and exclusion criteria used to select the articles were: (1) Human studies
      published in the English language; (2) Study published in international peer
      viewed journals; (3) Studies evaluated the association between KM width and the
      peri-implant tissue health; (4) Studies that have follow up of greater than 12
      months; (5) Publication of studies not older than 10 years. The searches
      retrieved 285 citations. Seven articles fulfilled all of the inclusion criteria.
      Out of these, three studies were ranked as presenting high methodological
      quality, and four were judged to be of moderate quality. This systematic review
      concludes that the presence of an adequate zone of keratinized tissue may be
      necessary because it was shown to be related to better peri-implant tissue
      health. Further randomized controlled trials are necessary to support this
      statement.

PMID- 24124022
TI  - Conditional prerequisites for microchannel cytologic analysis on wet mount (fluid
      based) biopsies.
AB  - BACKGROUND: Advanced capabilities in genomic sequencing developed in the research
      sector will soon enter the clinical arena. Issues such as the proportioning of
      patient specimen material for traditional bright-field microscopic evaluation or
      dedication for molecular analysis will intensify, particularly in situations of
      small core biopsies. Microfluidics appears aptly suited as a platform capable of
      allowing traditional cytologic diagnostics and downstream molecular analysis from
      the same specimen. However, clarification is needed to determine that forces
      which act on cells in a fluidic environment do not drastically alter their
      cytologic features. METHODS: Cells were processed for flow-through in a
      microfluidic channel and evaluated qualitatively and quantitatively for
      alterations due to fluid-shear stress or anoikis. RESULTS: Processing caused
      separation of cells from cohesive clusters to smaller groups and individual
      cells, leading to greater variation in parameters associated with the nucleus in
      nontumor cells but no significant change in tumor cells. These differences were
      most readily apparent by quantitative measures, and to a lesser extent,
      qualitative evaluation. Time-dependent processing played a larger role in
      cytologic alteration than fluid-shear stress for nontumor cells. CONCLUSIONS:
      Passage of cells through a microfluidic channel is a feasible approach that can
      be integrated into future platforms intent on integrating cytologic assessment of
      cells with recovery of the same cells for downstream assays.

PMID- 24124023
TI  - Prepregnancy body mass index and cardiovascular disease mortality: the Child
      Health and Development Studies.
AB  - OBJECTIVE: Overweight early in life may contribute to cardiovascular disease
      mortality through progression to later life obesity or through a cumulative
      effect of excess weight. Few studies have investigated the relationship between
      body mass index (BMI) before middle age and cardiovascular disease mortality in
      women. Using the Child Health and Development Studies cohort of 11,006 pregnant
      women recruited between 1959 and 1967, the hypothesis that higher self-reported
      prepregnancy BMI is associated with increased stroke and coronary heart disease
      mortality was tested. METHODS: Cause of death was assessed annually from
      enrollment through 2007 by linking with California Vital Status Records. Cox
      proportional hazards ratios for cause-specific mortality for each BMI category
      were calculated. RESULTS: Median follow-up was 37 years with 1839 participant
      deaths at a mean age of 64.1 years. At higher levels of BMI, participants were
      older, had higher prevalence of co-morbid conditions, higher parity, and lower
      family income. In adjusted models, women with higher prepregnancy BMI had
      increased coronary heart disease mortality compared to those with normal BMI.
      Women who were underweight, overweight, or obese had higher all-cause mortality.
      Sensitivity analyses confirmed these results. CONCLUSIONS: Prepregnancy BMI has a
      monotonic association with coronary heart disease mortality and a j-shaped
      association with noncardiovascular mortality.

PMID- 24124025
TI  - A simple and sensitive resonance Rayleigh scattering method for determination of
      As(III) using aptamer-modified nanogold as a probe.
AB  - A simple and selective aptamer (ssDNA)-modified nanogold probe (AussDNA) was
      prepared for the determination of trace As(III) in HEPES buffer solution (pH 8.2)
      containing 0.05 mol/L NaCl. The method coupled the aptamer reaction of AussDNA
      As(III) and the resonance Rayleigh scattering (RRS) of nanogold aggregations at
      278 nm. When the As(III) concentration increased, the RRS intensity at 278 nm
      increased to form more nanogold aggregation and a stable As(III)-ssDNA complex.
      Under selected conditions, the increased RRS intensity (DeltaI) was linear to the
      concentration of As(III) in the range 3.8-230.4 ng/mL, with a detection limit of
      1.9 ng/mL. This RRS method was applied to detect As(III) in water samples, with
      simplicity, sensitivity and selectivity.

PMID- 24124027
TI  - Present role of positron emission tomography in the diagnosis and monitoring of
      peripheral inflammatory arthritis: a systematic review.
AB  - OBJECTIVE: To determine the current status of positron emission tomography (PET)
      as a tool for diagnosis and monitoring of peripheral inflammatory arthritis (IA).
      METHODS: For conducting this systematic review, the PubMed (Medline), Embase, and
      Cochrane Library databases were searched until December 31, 2012. Studies of PET
      for diagnosis and/or therapy monitoring of peripheral IA were included. Data were
      summarized qualitatively using best evidence synthesis. RESULTS: Eighteen
      articles met our inclusion criteria. The majority of studies were feasibility
      studies with varying methods applied. All studies demonstrated that PET
      visualized IA with high sensitivity, corresponding to clinical assessments. PET
      outcome of clinically active IA also matched that of ultrasound and magnetic
      resonance imaging. PET differentiates from other modalities by (quantitative)
      imaging of molecular sites in the synovium. The first studies reporting on the
      potential clinical applications of PET to image subclinical synovitis in
      preclinical RA and during therapy have been published. The results are promising,
      but the number and study populations of these studies are still limited.
      CONCLUSION: Thus far, a limited number of PET studies addressing IA imaging have
      been published. The PET modality seems to offer highly sensitive and potentially
      specific imaging of IA at the (quantitative) molecular level. Clinical
      application studies for early diagnostics and therapy monitoring are arising, but
      these topics should be further explored in future studies with larger cohorts.
      For integration in clinical practice, aspects such as radiation burden and cost
      effectiveness should also be taken into account.

PMID- 24124028
TI  - The daily commute from work to home: examining employees' experiences in relation
      to their recovery status.
AB  - Sufficient recovery after daily effort expenditure at work is important to
      protect employee health and well-being. However, the role of commuting in the
      daily effort-recovery process is still not very well understood. The present
      study aimed to advance insight in this respect by examining if relaxation,
      detachment, mastery and stressful delays experienced during the commute from work
      to home affect employees' recovery status after returning home from work and at
      the end of the evening. Daily job demands were expected to moderate these
      effects. Serenity and (low) anxiety were included as indicators of employees'
      recovery status. Data were collected by means of a 5-day daily diary study (three
      measurements daily) among 76 participants from various industries. Multilevel
      analyses showed that relaxation was positively and stressful delays were
      negatively related to employees' recovery status after returning home from work
      but not to indicators of recovery at the end of the evening. For detachment,
      similar relations were found but only on days with high job demands. Mastery was
      not related to employees' recovery status. These findings enhance our insight in
      the daily effort-recovery cycle and underline the importance of promoting
      detachment (on demanding workdays) and relaxation on the way home from work.

PMID- 24124029
TI  - Production of cellulase-free xylanase by the recombinant Bacillus subtilis and
      its applicability in paper pulp bleaching.
AB  - A metagenomic xylanase gene (Mxyl) was successfully cloned into shuttle vector
      pWH1520 and expressed in Bacillus subtilis extracellularly. On induction with
      xylose, recombinant xylanase secretion commenced after 6 h. Identifying critical
      variables for recombinant xylanase production by one-variable-at-time approach
      followed by optimization of the selected variables (xylose, inoculum density,
      incubation density) by response surface methodology (RSM) led to three-fold
      enhancement in extracellular xylanase production (119 U mL(-1) ). When the pulp
      was treated with recombinant xylanase at 80 degrees C and pH 9.0, kappa number of
      the pulp was reduced with concomitant increase in brightness and 24% reduction in
      chlorine consumption. This is the first report on the expression of metagenomic
      xylanase gene in Bacillus subtilis extracellularly and its utility in developing
      an environment-friendly pulp bleaching process.

PMID- 24124024
TI  - Modeling anterior development in mice: diet as modulator of risk for neural tube
      defects.
AB  - Head morphogenesis is a complex process that is controlled by multiple signaling
      centers. The most common defects of cranial development are craniofacial defects,
      such as cleft lip and cleft palate, and neural tube defects, such as anencephaly
      and encephalocoele in humans. More than 400 genes that contribute to proper
      neural tube closure have been identified in experimental animals, but only very
      few causative gene mutations have been identified in humans, supporting the
      notion that environmental influences are critical. The intrauterine environment
      is influenced by maternal nutrition, and hence, maternal diet can modulate the
      risk for cranial and neural tube defects. This article reviews recent progress
      toward a better understanding of nutrients during pregnancy, with particular
      focus on mouse models for defective neural tube closure. At least four major
      patterns of nutrient responses are apparent, suggesting that multiple pathways
      are involved in the response, and likely in the underlying pathogenesis of the
      defects. Folic acid has been the most widely studied nutrient, and the diverse
      responses of the mouse models to folic acid supplementation indicate that folic
      acid is not universally beneficial, but that the effect is dependent on genetic
      configuration. If this is the case for other nutrients as well, efforts to
      prevent neural tube defects with nutritional supplementation may need to become
      more specifically targeted than previously appreciated. Mouse models are
      indispensable for a better understanding of nutrient-gene interactions in normal
      pregnancies, as well as in those affected by metabolic diseases, such as diabetes
      and obesity.

PMID- 24124030
TI  - Estimating the frequency of Cry1F resistance in field populations of the European
      corn borer (Lepidoptera: Crambidae).
AB  - BACKGROUND: Transgenic corn hybrids that express toxins from Bacillus
      thuringiensis (Bt) have suppressed European corn borer populations and reduced
      the pest status of this insect throughout much of the US corn belt. A major
      assumption of the high-dose/refuge strategy proposed for insect resistance
      management and Bt corn is that the frequency of resistance alleles is low so that
      resistant pests surviving exposure to Bt corn will be rare. RESULTS: The
      frequency of resistance to the Cry1F Bt toxin was estimated using two different
      screening tools and compared with annual susceptibility monitoring based on
      diagnostic bioassays and LC50 and EC50 determinations. An F1 screening approach
      where field-collected individuals were mated to a resistant laboratory strain and
      progeny were assayed to determine genotype revealed that resistance alleles could
      be recovered even during the first year of commercially available Cry1F corn
      (2003). Estimates of frequency from 2003-2005 and 2006-2008 indicated that,
      although allele frequency was higher than theoretical assumptions (0.0286 and
      0.0253 respectively), there was no indication that the frequency was increasing.
      Similar estimates in 2008 and 2009 using an F2 screening approach confirmed the
      presence of non-rare resistance alleles (frequency ~ 0.0093 and 0.0142 for 2008
      and 2009, respectively). The results of both screening methods were in general
      agreement with the observed mortality in diagnostic bioassays and LC50 and EC50
      determinations. CONCLUSIONS: These results are consistent with previous modeling
      results, suggesting that the high-dose/refuge strategy that is in place for Bt
      corn may be effective in delaying resistance evolution even when a relatively
      high frequency of resistance alleles exists.

PMID- 24124031
TI  - Column comparison and method development for the analysis of short-chain
      carboxylic acids by zwitterionic hydrophilic interaction liquid chromatography
      with UV detection.
AB  - Short-chain carboxylic acids are relevant in pharmaceutical, food quality
      control, and biomedical analysis. In this study, 11 acids commonly found in drugs
      and in food products were selected. Wine was chosen as matrix for testing the
      method. The test compounds were used for comparing the selectivity of four 150 *
      2.1 mm zwitterionic hydrophilic interaction LC (HILIC) columns (ZIC-HILIC 5 MUm,
      200 A, and 3.5 MUm, 100 A, ZIC-pHILIC 5 MUm, ZIC-cHILIC 3 MUm, 100 A) while
      varying the conditions to optimize for low UV wavelength detection and achieve
      high sensitivity. Retention using potassium phosphate and ammonium carbonate as
      mobile-phase components at pH 6.0, 7.5, and 8.5-8.9 was studied considering
      recent hypotheses on HILIC mechanism-related with the Hofmeister series effect
      and ion hydration. An isocratic method with UV detection at 200 nm and mobile
      phase consisting of 75% acetonitrile and 10 mM potassium phosphate at pH 6.0
      applied to a ZIC-cHILIC column was found provisionally optimal and partially
      validated for the 11 analytes. Satisfactory results (R(2) from 0.9940 to
      >0.9999), and recoveries from 93-106% for all analytes evidenced the method as
      suitable for wine analysis. To the best of our knowledge, no previous study has
      reported on the direct ZIC-HILIC separation and UV detection of the acids
      considered here in wine. 

PMID- 24124032
TI  - The patient care circle: a descriptive framework for understanding care
      transitions.
AB  - BACKGROUND: Reducing hospital readmissions depends on ensuring safe care
      transitions, which requires a better understanding of the challenges experienced
      by key stakeholders. OBJECTIVE: Develop a descriptive framework illustrating the
      interconnected roles of patients, providers, and caregivers in relation to
      readmissions. DESIGN: Multimethod qualitative study with 4 focus groups and 43
      semistructured interviews. Multiple perspectives were included to increase the
      trustworthiness (internal validity) and transferability (external validity) of
      the results. Data were analyzed using grounded theory to generate themes
      associated with readmission. SETTING/PATIENTS: General medicine patients with
      same-site 30-day readmissions, their family members, and multiple care providers
      at a large urban academic medical center. RESULTS: A keynote generated from the
      multiperspective responses was that care transitions were optimized by a well
      coordinated multidiscipline support system, described as the Patient Care Circle.
      In addition, issues pertaining to readmissions were identified and classified
      into 5 main themes emphasizing the necessity of a coordinated support network:
      (1) teamwork, (2) health systems navigation and management, (3) illness severity
      and health needs, (4) psychosocial stability, and (5) medications. CONCLUSION: A
      well-coordinated collaborative Patient Care Circle is fundamental to ensuring
      safe care transitions.

PMID- 24124033
TI  - AOD-9604 does not influence the WADA hGH isoform immunoassay.

PMID- 24124034
TI  - Cornelia de Lange individuals with new and recurrent SMC1A mutations enhance
      delineation of mutation repertoire and phenotypic spectrum.
AB  - We report on the clinical and molecular characterization of eight patients, one
      male and seven females, with clinical diagnosis of Cornelia de Lange syndrome
      (CdLS), who were found to carry distinct mutations of the SMC1A gene. Five of the
      eight mutations are novel, with two involving amino acid residues previously
      described as altered in a different way. The other three have been reported each
      in a single case. Comparison of pairs of individuals with the same mutation
      indicates only partial overlap of their clinical phenotypes. The following novel
      missense mutations, all affecting highly conserved amino acid residues, were
      found: p.R398G in the N-terminal coiled-coil domain, p.V651M in the C-terminal
      coiled-coil/hinge junction, p.R693G in the C-terminal coiled-coil, and p.N1166T
      and p.L1189F in the C-terminal ABC cassette. The latter is localized in the H
      loop, and represents the first mutation involving a functional motif of SMC1A
      protein. The effect of the mutations on SMC1A protein function has been predicted
      using four bioinformatic tools. All mutations except p.V651M were scored as
      pathogenic by three or four of the tools. p.V651M was found in the only male
      individual of our cohort, who presented with the most severe phenotype. This
      raises the issue of gender effect when addressing mutation-phenotype correlation
      for genes such as SMC1A, which incompletely escapes X-inactivation. Our clinical
      and molecular findings expand the total number of characterized SMC1A-mutated
      patients (from 44 to 52) and the restricted repertoire of SMC1A mutations (from
      29 to 34), contributing to the molecular and clinical signature of SMC1A-based
      CdLS.

PMID- 24124035
TI  - The financial cost of hamstring strain injuries in the Australian Football
      League.
AB  - BACKGROUND: Hamstring strain injuries (HSIs) have remained the most prevalent
      injury in the Australian Football League (AFL) over the past 21 regular seasons.
      The effect of HSIs in sports is often expressed as regular season games missed
      due to injury. However, the financial cost of athletes missing games due to
      injury has not been investigated. The aim of this report is to estimate the
      financial cost of games missed due to HSIs in the AFL. METHOD: Data were
      collected using publicly available information from the AFL's injury report and
      the official AFL annual report for the past 10 competitive AFL seasons. Average
      athlete salary and injury epidemiology data were used to determine the average
      yearly financial cost of HSIs for AFL clubs and the average financial cost of a
      single HSI over this time period. RESULTS: Across the observed period, average
      yearly financial cost of HSIs per club increased by 71% compared with a 43%
      increase in average yearly athlete salary. Over the same time period the average
      financial cost of a single HSI increased by 56% from $A25,603 in 2003 to $A40,021
      in 2012, despite little change in the HSI rates during the period. CONCLUSIONS:
      The observed increased financial cost of HSIs was ultimately explained by the
      failure of teams to decrease HSI rates, but coupled with increases in athlete
      salaries over the past 10 season. The information presented in this report
      highlights the financial cost of HSIs and other sporting injuries, raising
      greater awareness and the need for further funding for research into injury
      prevention strategies to maximise economical return for investment in athletes.

PMID- 24124036
TI  - What helps children to move more at school recess and lunchtime? Mid-intervention
      results from Transform-Us! cluster-randomised controlled trial.
AB  - BACKGROUND: To investigate the interpersonal and physical environment mediators
      of the Transform-Us! mid-intervention effects on physical activity (PA) during
      recess and lunchtime. METHODS: Transform-Us! is a clustered randomised school
      based intervention with four groups: sedentary behaviour intervention (SB-I), PA
      intervention (PA-I), combined PA+SB-I and control group. All children in grade 3
      from 20 participating primary schools in Melbourne, Australia were eligible to
      complete annual evaluation assessments. The outcomes were the proportion of time
      spent in moderate-to-vigorous PA (MVPA) and light PA (LPA) during recess and
      lunchtime assessed by accelerometers. Potential mediators included: perceived
      social support from teachers; perceived availability of line markings; perceived
      accessibility of sports equipment; and perceived school play environment.
      Generalised linear models were used and mediation effects were estimated by
      product-of-coefficients (a.b) approach. RESULTS: 268 children (8.2 years, 57%
      girls at baseline) provided complete data at both time points. A significant
      intervention effect on MVPA during recess in the SB-I and PA-I groups compared
      with the control group (proportional difference in MVPA time; 38% (95% CI 21% to
      57%) and 40% (95% CI 20% to 62%), respectively) was found. The perceived school
      play environment was significantly positively associated with MVPA at recess
      among girls. An increase in perceived social support from teachers suppressed the
      PA+SB-I effect on light PA during recess (a.b= -0.03, 95% CI -0.06 to -0.00). No
      significant mediating effects on PA during recess and lunchtime were observed.
      CONCLUSIONS: A positive perception of the school play environment was associated
      with higher MVPA during recess among girls. Future studies should conduct
      mediation analyses to explore underlying mechanisms of PA interventions.

PMID- 24124037
TI  - Outcomes from sudden cardiac arrest in US high schools: a 2-year prospective
      study from the National Registry for AED Use in Sports.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is the leading cause of death in athletes
      during exercise. The effectiveness of school-based automated external
      defibrillator (AED) programmes has not been established through a prospective
      study. METHODS: A total of 2149 high schools participated in a prospective
      observational study beginning 1 August 2009, through 31 July 2011. Schools were
      contacted quarterly and reported all cases of SCA. Of these 95% of schools
      confirmed their participation for the entire 2-year study period. Cases of SCA
      were reviewed to confirm the details of the resuscitation. The primary outcome
      was survival to hospital discharge. RESULTS: School-based AED programmes were
      present in 87% of participating schools and in all but one of the schools
      reporting a case of SCA. Fifty nine cases of SCA were confirmed during the study
      period including 26 (44%) cases in students and 33 (56%) in adults; 39 (66%)
      cases occurred at an athletic facility during training or competition; 55 (93%)
      cases were witnessed and 54 (92%) received prompt cardiopulmonary resuscitation.
      A defibrillator was applied in 50 (85%) cases and a shock delivered onsite in 39
      (66%). Overall, 42 of 59 (71%) SCA victims survived to hospital discharge,
      including 22 of 26 (85%) students and 20 of 33 (61%) adults. Of 18 student
      athletes 16 (89%) and 8 of 9 (89%) adults who arrested during physical activity
      survived to hospital discharge. CONCLUSIONS: High school AED programmes
      demonstrate a high survival rate for students and adults who suffer SCA on school
      campus. School-based AED programmes are strongly encouraged.

PMID- 24124038
TI  - Chronic traumatic encephalopathy: rugby's call for clarity, data and leadership
      in the concussion debate.

PMID- 24124039
TI  - Mechanical instability destabilises the ankle joint directly in the ankle-sprain
      mechanism.
AB  - BACKGROUND: Despite massive research efforts, it remains unclear how mechanical
      ankle instability (MAI) and functional ankle instability (FAI) affect joint
      control in the situation of ankle sprain. Thus, the purpose of this study was to
      evaluate whether individuals with MAI have deficits in stabilising their ankle
      joint in a close-to-injury situation compared with those with FAI and healthy
      controls. METHODS: Ankle-joint control was assessed by means of three-dimensional
      motion analysis and electromyography in participants with FAI and MAI (n=19), in
      participants with pure FAI (n=9) and in healthy controls (n=18). Close-to-injury
      situations were simulated during standing, walking and jumping by means of a
      custom-made tilt platform. RESULTS: Individuals with FAI and MAI displayed
      significantly greater maximum ankle inversion angles (+5 degrees ) and inversion
      velocities (+50 degrees /s) in the walking and jumping conditions compared to
      those with pure FAI and controls. Furthermore, individuals in the FAI and MAI
      group showed a significantly decreased pre-activation of the peroneus longus
      muscle during jumping compared to those with FAI. No differences between groups
      were found for plantar flexion and internal rotation, or for muscle activities
      following tilting of the platform. CONCLUSIONS: The present study demonstrates
      that MAI is characterised by impairments of ankle-joint control in close-to
      injury situations. This could make these individuals more prone to recurrent
      ankle sprains, and suggests the need for additional mechanical support such as
      braces or even surgery. In addition, the study highlights the fact that dynamic
      experimental test conditions in the acting participant are needed to further
      unravel the mystery of chronic ankle instability.

PMID- 24124041
TI  - Visuospatial anatomy comprehension: the role of spatial visualization ability and
      problem-solving strategies.
AB  - The present study explored the problem-solving strategies of high- and low
      spatial visualization ability learners on a novel spatial anatomy task to
      determine whether differences in strategies contribute to differences in task
      performance. The results of this study provide further insights into the
      processing commonalities and differences among learners beyond the classification
      of spatial visualization ability alone, and help elucidate what, if anything,
      high- and low-spatial visualization ability learners do differently while solving
      spatial anatomy task problems. Forty-two students completed a standardized
      measure of spatial visualization ability, a novel spatial anatomy task, and a
      questionnaire involving personal self-analysis of the processes and strategies
      used while performing the spatial anatomy task. Strategy reports revealed that
      there were different ways students approached answering the spatial anatomy task
      problems. However, chi-square test analyses established that differences in
      problem-solving strategies did not contribute to differences in task performance.
      Therefore, underlying spatial visualization ability is the main source of
      variation in spatial anatomy task performance, irrespective of strategy. In
      addition to scoring higher and spending less time on the anatomy task,
      participants with high spatial visualization ability were also more accurate when
      solving the task problems.

PMID- 24124040
TI  - Variables associated with return to sport following anterior cruciate ligament
      reconstruction: a systematic review.
AB  - BACKGROUND: As one of the purposes of anterior cruciate ligament reconstruction
      (ACLR) is to return athletes to their preinjury activity level, it is critical to
      understand variables influencing return to sport. Associations between return to
      sport and variables representing knee impairment, function and psychological
      status have not been well studied in athletes following ACLR. PURPOSE: The
      purpose of this review was to summarise the literature reporting on variables
      proposed to be associated with return to sport following ACLR. STUDY DESIGN:
      Systematic review. METHODS: Medline, EMBASE, CINAHL and Cochrane databases were
      searched for articles published before November 2012. Articles included in this
      review met these criteria: (1) included patients with primary ACLR, (2) reported
      at least one knee impairment, function or psychological measure, (3) reported a
      return to sport measure and (4) analysed the relationship between the measure and
      return to sport. RESULTS: Weak evidence existed in 16 articles suggesting
      variables associated with return to sport included higher quadriceps strength,
      less effusion, less pain, greater tibial rotation, higher Marx Activity score,
      higher athletic confidence, higher preoperative knee self-efficacy, lower
      kinesiophobia and higher preoperative self-motivation. CONCLUSIONS: Weak evidence
      supports an association between knee impairment, functional and psychological
      variables and return to sport. Current return to sport guidelines should be
      updated to reflect all variables associated with return to sport. Utilising
      evidence-based return to sport guidelines following ACLR may ensure that athletes
      are physically and psychologically capable of sports participation, which may
      reduce reinjury rates and the need for subsequent surgery.

PMID- 24124042
TI  - Subcutaneous immunoglobulin therapy for inflammatory neuropathy: current evidence
      base and future prospects.
AB  - Intravenous immunoglobulin therapy is of proven effect in chronic inflammatory
      neuropathies, including chronic inflammatory demyelinating polyneuropathy (CIDP)
      and multifocal motor neuropathy (MMN). In more recent years, there have been a
      number of anecdotal case reports and small series, followed by a few trials of
      variable design, of subcutaneous immunoglobulin therapy in these neuropathies. To
      date, limited evidence suggests that the subcutaneous route may be a more
      clinically effective, better-tolerated, at least cost-equivalent and a more
      patient-friendly option than the still more used intravenous alternative. Long
      term efficacy is not as yet established in neuropathic indications by randomised
      controlled clinical trial evidence, and it is likely that the subcutaneous route
      may not be suitable in all cases with some hints to this effect appearing from
      the limited data available to date. Further studies are ongoing, including those
      of dose comparison, and more are likely to be planned in future. The literature
      on the use of subcutaneous immunoglobulin therapy in chronic inflammatory
      neuropathy is reviewed here. The current use in clinical practice, day-to-day
      benefits, including quality of life measures and health economics as published
      thus far, are evaluated. The limitations of this form of treatment in CIDP and
      MMN are also analysed in the light of current literature and taking into account
      the remaining unknowns. Future prospects and research with this mode of
      immunoglobulin therapy administration are discussed. 

PMID- 24124043
TI  - Specialist inpatient treatment for severe motor conversion disorder: a
      retrospective comparative study.
AB  - BACKGROUND: Gold standard protocols have yet to be established for the treatment
      of motor conversion disorder (MCD). There is limited evidence to support
      inpatient, multidisciplinary intervention in chronic, severe cases. AIMS: To
      evaluate the characteristics and outcomes of MCD patients admitted to a
      specialist neuropsychiatric inpatient unit. METHODS: All patients admitted to the
      Lishman Unit (years 2007-2011) with a diagnosis of MCD were included. Data
      relevant to characteristics and status with regard to mobility, activities of
      daily living (ADLs) and Modified Rankin Scale (MRS) score at admission and
      discharge were extracted. RESULTS: Thirty-three cases (78.8% female) were
      included; the median duration of illness was 48 months. In comparison with brain
      injury patients admitted to the same unit, more cases had histories of childhood
      sexual abuse (36.4%, n=12), premorbid non-dissociative mental illness (81.1%,
      n=27) and employment as a healthcare/social-care worker (45.5%, n=15). Cases
      showed significant improvements in MRS scores (p<0.001), mobility (p<0.001) and
      ADL (p=0.002) following inpatient treatment. CONCLUSIONS: Patients with severe,
      long-standing MCD can achieve significant improvements in functioning after
      admission to a neuropsychiatry unit.

PMID- 24124044
TI  - Acute bilateral visual loss in a young adult.

PMID- 24124045
TI  - Treatment and outcomes of chronic rhinosinusitis in children with primary ciliary
      dyskinesia: where is the evidence? A qualitative systematic review.
AB  - BACKGROUND: Consensus on treatment of chronic rhinosinusitis (CRS) in children
      with primary ciliary dyskinesia (PCD) is limited. We sought to synthesize the
      best available evidence pertaining to treatment and outcomes of CRS in children
      with PCD. METHODS: This work is a systematic review of PubMed and EMBASE for
      studies pertaining to treatment and outcomes of CRS in children with PCD in a 20
      year period. Two reviewers independently extracted information on study design,
      setting, medical or surgical therapy for CRS, and treatment outcomes. RESULTS:
      Twelve studies from 8 countries were included for analysis: (3 retrospective
      cohorts, 2 prospective cohorts, 2 cross-sectional, 1 case series, and 4 case
      reports). The number of patients with PCD ranged from 1 to 78. Medical treatment
      included oral antibiotics, intranasal steroids, and oral steroids. Surgical
      treatment was mentioned in 8 studies, with endoscopic sinus surgery (ESS)
      described in 3 of 8. Outcome measures were rarely defined but included the 20
      item Sino-Nasal Outcome Test (SNOT-20) questionnaire (1/12), symptom
      questionnaire (1/12), decreased recurrent pneumonia (1/12), and subjective report
      of CRS symptoms. No randomized, controlled, or long-term prospective cohort
      studies were identified, and no study employed a disease-specific, pediatric
      validated instrument to measure outcomes of therapy. CONCLUSION: There is a
      paucity of evidence pertaining to CRS treatment or outcomes in children with PCD.
      Given the rare prevalence of PCD and the insufficient evidence pertaining to
      treatment effectiveness for CRS, we propose an international, multicenter
      database to prospectively track data pertaining to diagnosis, treatment, and
      outcomes of CRS for children with PCD. This effort would encourage implementation
      of validated and standardized outcome measures.

PMID- 24124048
TI  - Storage of potassium ions in layered vanadium pentoxide nanofiber electrodes for
      aqueous pseudocapacitors.
AB  - Spaced out: This paper investigates potassium-ion storage in vanadium pentoxide
      nanofibers (VNFs, K0.33 V2 O5 ) with a layered architecture. In situ XRD
      experiments reveal that the interplanar space of VNF expands/contracts upon
      extraction/insertion of potassium ions during the redox process. 

PMID- 24124049
TI  - How to use published complete case results from weight loss studies in a missing
      data sensitivity analysis.
AB  - OBJECTIVE: In randomized controlled trials of weight loss interventions, high
      dropout rates are a problem resulting in a large amount of missing outcome data.
      It is common for participants with missing data to be excluded from analysis
      (complete-case analysis). The aim of this article is to demonstrate how published
      complete-case results can be used to explore how study results would change
      depending on assumptions about dropout weight loss. METHODS: The methods are
      based on three extensions to a method for obtaining baseline observation carried
      forward (BOCF) results from complete-case results. The first extension is a
      generalization to any dropout weight loss. Second, to show that it is not
      necessary to assume that dropout weight loss is the same in each treatment arm.
      Third, to show that variation in dropout weight loss can be incorporated. Using
      these extensions, sensitivity analyses to the missing data can be conducted via
      the use of plots. RESULTS: The methods are demonstrated using two examples of
      published results from studies of weight loss interventions. It is also shown how
      the BOCF method could be useful to meta-analysts. CONCLUSION: By using simple
      plots, readers can explore how different assumptions about dropout weight loss
      affect the results of published weight loss trials.

PMID- 24124047
TI  - Genetics of cleft lip and cleft palate.
AB  - Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic
      events or as part of Mendelian syndromes. There is substantial phenotypic
      diversity in individuals with these birth defects and their family members: from
      subclinical phenotypes to associated syndromic features that is mirrored by the
      many genes that contribute to the etiology of these disorders. Identification of
      these genes and loci has been the result of decades of research using multiple
      genetic approaches. Significant progress has been made recently due to advances
      in sequencing and genotyping technologies, primarily through the use of whole
      exome sequencing and genome-wide association studies. Future progress will hinge
      on identifying functional variants, investigation of pathway and other
      interactions, and inclusion of phenotypic and ethnic diversity in studies.

PMID- 24124050
TI  - The effect of antiapoptosis genes on clarification performance.
AB  - Optimal bioreactor harvest time is typically determined based on maximizing
      product titer without compromising product quality. We suggest that ease of
      downstream purification should also be considered during harvest. In this view,
      we studied the effect of antiapoptosis genes on downstream performance. Our
      hypothesis was that more robust cells would exhibit less cell lysis and thus
      generate lower levels of cell debris and host-cell contaminants. We focused on
      the clarification unit operation, measuring postclarification turbidity and host
      cell protein (HCP) concentration as a function of bioreactor harvest time/cell
      viability. In order to mimic primary clarification using disk-stack
      centrifugation, a scale-down model consisting of a rotating disk (to simulate
      shear in the inlet feed zone of the centrifuge) and a swinging-bucket lab
      centrifuge was used. Our data suggest that in the absence of shear during primary
      clarification (typical of depth filters), a 20-50% reduction in HCP levels and 50
      65% lower postcentrifugation turbidity was observed for cells with antiapoptosis
      genes compared to control cells. However, on exposing the cells to shear levels
      typical in a disk-stack centrifuge, the reduction in HCP was 10-15% while no
      difference in postcentrifugation turbidity was observed. The maximum benefit of
      antiapoptosis genes is, therefore, realized using clarification options that
      involve low shear, <1 * 10(6) W/m(3) and minimal damage to the cells.

PMID- 24124052
TI  - Cost-effectiveness of total knee replacement: a prospective cohort study.
AB  - OBJECTIVE: Total knee replacement (TKR) rates have significantly increased in the
      past decade. While the procedure itself might be costly, the cost-effectiveness
      and potential offset costs from patient and societal benefits have not been
      clearly established. The objective of this study was to perform an economic
      evaluation of TKR in patients with knee osteoarthritis (OA). METHODS: We
      conducted a 6-month prospective cohort study of 212 patients with knee OA who
      underwent TKR at a single hospital in Houston, Texas. We included patient-level
      data from hospital billing databases and the patients' self-reported direct and
      indirect costs. The clinical outcome measure was pain and function measured by
      the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      questionnaire; we used the minimum clinically important difference (MCID; >=20
      point change) and the WOMAC 20% (WOMAC20), 50% (WOMAC50), and 70% (WOMAC70)
      relative improvement criteria. Incremental cost-effectiveness ratios were
      estimated using direct and indirect costs and WOMAC improvement. A societal
      perspective was used and multiple sensitivity analyses were performed to assess
      the robustness of the principal analysis. RESULTS: The total incremental cost per
      TKR was $20,133. The incremental cost-effectiveness ratios (ICERs) for
      improvement at 6 months were $33,345, $25,255, $35,274, and $56,908 for the MCID,
      WOMAC20, WOMAC50, and WOMAC70, respectively. Best- and worst-case scenario
      sensitivity analyses did not have a significant impact on the ICERs. Patient time
      lost was the most influential variable in the multiway sensitivity analysis.
      CONCLUSION: TKR is an effective intervention in reducing pain and improving
      functional status among patients with knee OA and is cost effective at both low
      and high levels of improvement.

PMID- 24124051
TI  - Instruction of haematopoietic lineage choices, evolution of transcriptional
      landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model.
AB  - The t(8;21) chromosomal translocation activates aberrant expression of the AML1
      ETO (AE) fusion protein and is commonly associated with core binding factor acute
      myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely
      resembles the slow evolution and the mosaic AE expression pattern of human
      t(8;21) CBF AML with global transcriptome sequencing, we find that disease
      progression was characterized by two principal pathogenic mechanisms. Initially,
      AE expression modified the lineage potential of haematopoietic stem cells (HSCs),
      resulting in the selective expansion of the myeloid compartment at the expense of
      normal erythro- and lymphopoiesis. This lineage skewing was followed by a second
      substantial rewiring of transcriptional networks occurring in the trajectory to
      manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte
      macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being
      capable of initiating and maintaining the disease. Finally, our data demonstrate
      that long-term expression of AE induces an indolent myeloproliferative disease
      (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute
      inactivation of AE function is a potential novel therapeutic option. 

PMID- 24124053
TI  - Identifying potential predictors of a safe attending physician workload: a survey
      of hospitalists.

PMID- 24124054
TI  - Systematic investigation of the incorporation mechanisms of zolpidem in
      fingernails.
AB  - Nails are attracting increasing interest in forensic toxicology as an alternative
      to hair. The goal of this study was to systematically investigate the
      incorporation of drugs in fingernails after single drug dose, exemplified for
      zolpidem. Fingernail samples from ring fingers were collected one week before,
      and then 24 h and weekly after intake for a period of three to five months. Hair
      samples were taken six weeks after intake. Nail specimens were pulverized and
      extracted with methanol (internal standard: zolpidem-D6 ) under sonication.
      Extracts were analyzed by a liquid chromatography-electrospray ionization-tandem
      mass spectrometry (LC-ESI-MS/MS) method, which was developed and validated for
      this study. The lower limit of quantification (LLOQ) for a 5-mg sample was 0.1
      pg/mg nail. Zolpidem was detected continuously in fingernail clippings. The mean
      window of detection of zolpidem in fingernail clippings was 3.5 months. Unwashed
      nail specimens taken 24 h after intake showed the highest zolpidem concentrations
      indicating external contamination by sweat. External contamination experiments
      revealed that zolpidem could be incorporated in fingernails by sweat to such an
      extent that it remained irremovable by daily hygiene. Averagely 3 months after
      intake a concentration peak was reached, suggesting outgrowth of the nail part
      which had been formed while the drug circulated in blood. Hair concentrations
      were higher than the maximum nail concentrations. Pigmented hair contained more
      zolpidem than non-pigmented hair from the same strand. From all these results it
      can be concluded, that fingernail clippings may represent a useful alternative
      and/or complementary matrix in cases of, for example, drug-facilitated sexual
      assault or monitoring of constant consumption behavior.

PMID- 24124055
TI  - A specific deficit of imitation in autism spectrum disorder.
AB  - Imitation is a potentially crucial aspect of social cognitive development.
      Although deficits in imitation ability have been widely demonstrated in autism
      spectrum disorder (ASD), the specificity and significance of the findings is
      unclear, due largely to methodological limitations. We developed a novel
      assessment of imitation ability, using objective movement parameters (path length
      and action duration) derived from a touch-sensitive tablet laptop during drawing
      actions on an identical tablet. By direct comparison of the kinematics of a
      model's actions with those of the participant who observed them, measures of
      imitation accuracy were obtained. By replaying the end-point of the movement as a
      spot on the screen, imitation accuracy was compared against a "ghost control"
      condition, with no human actor but only the end-point of the movement seen
      [object movement reenactment (OMR)]. Hence, demands of the control task were
      closely matched to the experimental task with respect to motor, memory, and
      attentional abilities. Adolescents with ASD showed poorer accuracy for copying
      object size and action duration on both the imitation and OMR tasks, but were
      significantly more impaired for imitation of object size. Our results provide
      evidence that some of the imitation deficit in ASD is specific to a self-other
      mapping problem, and cannot be explained by general factors such as memory,
      spatial reasoning, motor control, or attention, nor related to the social demands
      of the testing situation.

PMID- 24124056
TI  - The effect of intranasal fluticasone propionate irrigations on salivary cortisol,
      intraocular pressure, and posterior subcapsular cataracts in postsurgical chronic
      rhinosinusitis patients.
AB  - BACKGROUND: Intranasal corticosteroid irrigations, especially budesonide, are
      used increasingly in the management of chronic rhinosinusitis. In post-endoscopic
      sinus surgery patients, irrigations may offer improved delivery at higher doses
      to the paranasal sinuses than intranasal spray preparations. Fluticasone
      propionate may have higher potency and lower systemic bioavailability than
      budesonide, but there is little data on its effects as an intranasal irrigation
      on the hypothalamic-pituitary-adrenal axis or on ocular findings. METHODS: Adult
      patients who had previously undergone bilateral endoscopic sinus surgery and had
      not taken systemic corticosteroids in the last 6 months were prospectively
      enrolled. Subjects irrigated with 3 mg of fluticasone propionate in 240 mL saline
      solution twice daily. Salivary cortisol, intraocular pressure, and the presence
      of posterior subcapsular cataracts were measured before drug administration and
      after 6 weeks of continuous use. RESULTS: Twenty-three subjects completed the
      study. No subjects had salivary cortisol levels below the normal range before or
      after therapy, and there was no statistical difference in mean salivary cortisol
      levels pretreatment and posttreatment (0.294 vs 0.392 MUg/dL; p = 0.27). There
      was no clinical or statistical difference in mean intraocular pressure before or
      after therapy (13.3 vs 13.3 mmHg; p = 0.86). No subjects developed a posterior
      subcapsular cataract. CONCLUSION: Fluticasone propionate irrigations did not
      suppress salivary cortisol levels or result in ocular changes. Irrigation with
      fluticasone propionate 3 mg in 240 mL saline twice daily may be a safe
      alternative to other intranasal or systemic corticosteroid treatments for chronic
      rhinosinusitis patients.

PMID- 24124059
TI  - The growing complexity of the intestinal polyposis syndromes.
AB  - Familial adenomatous polyposis has been the first form of inherited intestinal
      polyposis to be recognized. For a long time it has been considered the main
      polyposis syndrome, associated with an easily recognizable phenotype, with a
      marginal role attributed to a few very rare hamartomatous conditions. More
      recently, it has been gradually demonstrated that the intestinal polyposes
      encompass a range of conditions within a wide spectrum of disease severity, polyp
      histology, and extraintestinal manifestations. A growing number of genes and
      phenotypes has been identified, and heterogeneity of somatic molecular pathways
      underlying epithelial transformation in different syndromes and associated tumors
      has been documented. Increasing knowledge on the molecular bases and more
      widespread use of genetic tests has shown phenotypic overlaps between conditions
      that were previously considered distinct, highlighting diagnostic difficulties.
      With the advent of next generation sequencing, the diagnosis and the
      classification of these syndromes will be progressively based more on genetic
      testing results. However, the phenotypic variability documented among patients
      with mutations in the same genes cannot be fully explained by different
      expressivity, indicating a role for as yet unknown modifying factors. Until the
      latter will be identified, the management of patients with polyposis syndromes
      should be guided by both clinical and genetic findings.

PMID- 24124060
TI  - Acceleration of bone formation during fracture healing by injectable collagen
      powder and human basic fibroblast growth factor containing a collagen-binding
      domain from Clostridium histolyticum collagenase.
AB  - Growth factor delivered with implantable biomaterials has been used to both
      accelerate and ensure healing of open fractures in human patients. However, a
      major limitation of implantable biomaterials is the requirement for open surgical
      placement. Here, we developed an injectable collagen material-based bone
      formation system consisting of injectable collagen powder with fibril morphology
      and collagen triple helix conformation, and basic fibroblast growth factor (bFGF)
      fused to the collagen-binding domain (CBD) of Clostridium histolyticum
      collagenase. The affinity of the CBD towards collagen was confirmed by the
      results of collagen-binding assays. Moreover, the combination of the collagen
      binding-bFGF fusion protein (CB-bFGF) with injectable collagen powder induced
      bone formation at protein concentrations lower than those required for bFGF alone
      in mice fracture models. Taken together, these properties suggest that the CB
      bFGF/collagen powder composite is a promising injectable material for bone repair
      in the clinical setting.

PMID- 24124058
TI  - Developmental disorders of the dentition: an update.
AB  - Dental anomalies are common congenital malformations that can occur either as
      isolated findings or as part of a syndrome. This review focuses on genetic causes
      of abnormal tooth development and the implications of these abnormalities for
      clinical care. As an introduction, we describe general insights into the genetics
      of tooth development obtained from mouse and zebrafish models. This is followed
      by a discussion of isolated as well as syndromic tooth agenesis, including Van
      der Woude syndrome (VWS), ectodermal dysplasias (EDs), oral-facial-digital (OFD)
      syndrome type I, Rieger syndrome, holoprosencephaly, and tooth anomalies
      associated with cleft lip and palate. Next, we review delayed formation and
      eruption of teeth, as well as abnormalities in tooth size, shape, and form.
      Finally, isolated and syndromic causes of supernumerary teeth are considered,
      including cleidocranial dysplasia and Gardner syndrome.

PMID- 24124061
TI  - Examining behavioral processes through which lifestyle interventions promote
      weight loss: results from PREMIER.
AB  - OBJECTIVE: To examine the behavioral processes through which lifestyle
      interventions impacted weight loss. METHODS: The analyses were limited to
      overweight and obese Black and White adults randomized to a PREMIER lifestyle
      intervention (N = 501). Structural equation modeling was conducted to test the
      direct and indirect relationships of session attendance, days of self-monitoring
      diet and exercise, change in diet composition and exercise, and 6-month weight
      change. RESULTS: Greater session attendance was associated with increased self
      monitoring, which was in turn significantly related to reduction in percent
      energy from total fat consumed. Change in percent energy from fat and self
      monitoring was associated with 6-month percent change in weight. Both a decrease
      in fat intake and increase in self-monitoring are potential mediators of the
      relationship between attendance and weight change. CONCLUSIONS: The findings
      provide a reasonable model that suggests regular session attendance and use of
      behavioral strategies like self-monitoring are associated with improved
      behavioral outcomes that are associated with weight loss.

PMID- 24124062
TI  - Stability of amorphous silica-alumina in hot liquid water.
AB  - Herein, the hydrothermal stability of amorphous silica-alumina (ASA) is
      investigated under conditions relevant for the catalytic conversion of biomass,
      namely in liquid water at 200  degrees C. The hydrothermal stability of ASA is
      much higher than that of pure silica or alumina. Interestingly, the synthetic
      procedure used plays a major role in its resultant stability: ASA prepared by
      cogelation (CG) lost its microporous structure, owing to hydrolysis of the
      siloxane bonds, but the resulting mesoporous material still had a considerable
      surface area. ASA prepared by deposition precipitation (DP) contained a silicon
      rich core and an aluminum-rich shell. In hot liquid water, the latter structure
      was transformed into a layer of amorphous boehmite, which protected the particle
      from further hydrolysis. The surface area showed relatively minor changes during
      the transformation. Independent of the synthetic method used, the ASAs retained a
      considerable concentration of acid sites. The concentration of acid sites
      qualitatively followed the changes in surface area, but the changes were less
      pronounced. The performance of different ASAs for the hydrolysis of cellobiose
      into glucose is compared. 

PMID- 24124063
TI  - Who makes it to the base? Selection procedure for a physical activity trial
      targeting people with rheumatoid arthritis.
AB  - OBJECTIVE: To compare those who were finally included in a large well-defined
      sample of individuals with rheumatoid arthritis (RA) at target for a physical
      activity (PA) trial with those who were not. METHODS: In total, 3,152 individuals
      answered questionnaires on sociodemographic, disease-related, and psychosocial
      factors and PA levels. The differences between individuals making it to the
      baseline assessments and those who did not were analyzed in 3 steps. RESULTS: In
      a first step, 1,932 individuals were eligible for the trial if they were
      interested in participating, not physically active enough, and fluent in Swedish
      and if they were not participating in any other study. The participants were
      mainly younger women, had higher education and income, were more likely to live
      with children, and had better support for exercise and had higher outcome
      expectations of PA than the 1,208 ineligible individuals. In a second step, the
      286 individuals accepting participation had higher income and education, more
      support for exercise, less fear-avoidance beliefs, and higher outcome
      expectations of PA than the 1,646 individuals declining participation. In a third
      step, the 244 individuals assessed at baseline reported less fatigue than the 42
      withdrawing before assessment. CONCLUSION: To our knowledge, this is the first
      study describing the entire selection procedure, from a target sample for a PA
      trial to the sample assessed at baseline, in individuals with RA. Factors other
      than those related to the disease seemed to mainly determine participation and
      largely resembled determinants in the general population. Sociodemographic and
      psychosocial factors should be recognized as important for PA in people with RA.

PMID- 24124064
TI  - Kinetic characterization of galacto-oligosaccharide (GOS) synthesis by three
      commercially important beta-galactosidases.
AB  - Many beta-galactosidases show large differences in galacto-oligosaccharide (GOS)
      production and lactose hydrolysis. In this study, a kinetic model is developed in
      which the effect of lactose, glucose, galactose, and oligosaccharides on the oNPG
      converting activity of various beta-galactosidases is quantified. The use of oNPG
      as a competing substrate to lactose yields more information than can be obtained
      by examining only the conversion of lactose itself. The reaction rate with
      lactose or oligosaccharides as substrate relative to that with water as acceptor
      is much higher for the beta-galactosidase of Bacillus circulans than the
      bgalactosidases of Aspergillus oryzae and Kluyveromyces lactis. In addition, the
      beta-galactosidase of B.circulans has a high reaction rate with galactose as
      acceptor, in contrast to those of A. oryzae and K. lactis. The latter two are
      strongly inhibited by galactose. These differences explain why beta-galactosidase
      of B. circulans gives higher yields in GOS production than other beta
      galactosidases. Many of the reaction rate constants for the beta-galactosidase
      isoforms of B. circulans increase with increasing molecular weight of the
      isoform. This indicates that the largest isoform beta-gal-A is most active in GOS
      production. However, its hydrolysis rate is also much higher than that of the
      other isoforms, which results in a faster hydrolysis of oligosaccharides as well.

PMID- 24124065
TI  - The in vivo and in vitro metabolism and the detectability in urine of 3',4'
      methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a new pyrrolidinophenone
      type designer drug, studied by GC-MS and LC-MS(n.).
AB  - 3',4'-Methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a designer drug of
      the pyrrolidinophenone-type, was first seized in Germany in 2009. It was also
      identified in 'legal high' samples investigated in the UK. Therefore, the aim of
      the presented work was to identify its in vivo and in vitro phase I and II
      metabolites using gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-ion trap mass spectrometry (LC-MS(n) ). Furthermore, detectability
      of MDPBP in rat and human urine using standard urine screening approaches (SUSA)
      by GC-MS and LC-MS(n) was studied. The metabolites were isolated either directly
      or after enzymatic cleavage of conjugates by solid-phase extraction (C18, HCX).
      The metabolites were then analyzed and structures proposed after GC-MS (phase I)
      and LC-MS(n) (phase II). Based on these identified metabolites, the following
      main metabolic steps could be proposed: demethylenation followed by methylation
      of one hydroxy group, aromatic and side chain hydroxylation, oxidation of the
      pyrrolidine ring to the corresponding lactam as well as ring opening to the
      corresponding carboxylic acid. Furthermore, in rat urine after a typical user's
      dose as well as in human urine, mainly the metabolites could be detected using
      the authors' SUSA by GC-MS and LC-MS(n) . Thus, it should be possible to monitor
      an application of MDPBP assuming similar toxicokinetics in humans. Finally,
      CYP2C19 and CYP2D6 could be identified as the isoenzymes mainly responsible for
      demethylenation.

PMID- 24124068
TI  - Epistaxis: the factors involved in determining medicolegal liability.
AB  - BACKGROUND: The purpose of this study was to examine litigation involving
      epistaxis and analyze factors that determine liability. METHODS: Jury verdicts
      and settlements regarding cases involving epistaxis were gathered utilizing the
      Westlaw database. Factors involved in litigation gathered included demographics,
      defendant specialty, procedure, alleged cause of malpractice, outcome, monetary
      award, and other variables. RESULTS: A total of 26 cases were analyzed. The
      majority of cases (57.7%) were decided in favor of the plaintiff or settled out
      of court. Total awards amounted to $24,501,252. Average awards for cases decided
      in favor of the plaintiff were $2,260,893 and ranged from $499,845 to $9,022,643.
      Settlements averaged $1,084,375 and ranged from $300,000 to $3,800,000. Common
      causes of malpractice encountered included delay in diagnosis, complications from
      medical procedures, and failure to recognize complications in a timely manner.
      CONCLUSION: Contrary to previous reports analyzing malpractice for varying
      medical procedures and complications, litigation in epistaxis is more commonly
      resolved in favor of the plaintiff or resolved through out-of-court settlements.
      Substantial financial awards and therapeutic complications from blindness to
      death make epistaxis a candidate for litigation. Of importance from a medicolegal
      stand is the fact that 30.8% (8) of the patients involved in epistaxis litigation
      died, either from complications of therapy or from experiencing epistaxis as a
      complication of another procedure/pathology. Using necessary diagnostic imaging,
      ensuring proper management techniques, and recognizing complications in a timely
      manner can serve to limit legal liability and enhance patient safety.

PMID- 24124067
TI  - Minimally verbal school-aged children with autism spectrum disorder: the
      neglected end of the spectrum.
AB  - It is currently estimated that about 30% of children with autism spectrum
      disorder remain minimally verbal, even after receiving years of interventions and
      a range of educational opportunities. Very little is known about the individuals
      at this end of the autism spectrum, in part because this is a highly variable
      population with no single set of defining characteristics or patterns of skills
      or deficits, and in part because it is extremely challenging to provide reliable
      or valid assessments of their developmental functioning. In this paper, we
      summarize current knowledge based on research including minimally verbal
      children. We review promising new novel methods for assessing the verbal and
      nonverbal abilities of minimally verbal school-aged children, including eye
      tracking and brain-imaging methods that do not require overt responses. We then
      review what is known about interventions that may be effective in improving
      language and communication skills, including discussion of both nonaugmentative
      and augmentative methods. In the final section of the paper, we discuss the gaps
      in the literature and needs for future research.

PMID- 24124069
TI  - Evidence review: periprocedural use of blood products.
AB  - Blood product transfusion has not been subject to rigorous clinical study, and
      great practice variations exist. Of particular concern to hospitalists is the use
      of red blood cells, plasma, and platelets prior to invasive procedures to correct
      anemia or perceived bleeding risk. We summarize the known risks associated with
      periprocedural anemia, prolonged international normalized ratio (INR), and
      thrombocytopenia, as well as the effects of blood product administration on
      clinical outcomes. Clinical trial evidence argues for a restrictive red blood
      cell transfusion threshold (a hemoglobin level of 7-8 g/dL or symptomatic anemia)
      for most perioperative patients. There are no high-quality data to guide plasma
      and platelet transfusions around the time of procedures. Available data do not
      support the use of prothrombin time/INR to guide prophylactic administration of
      plasma, and there are scarce data to guide platelet use around the time of an
      invasive procedure. Therefore, we rely on current consensus expert opinion, which
      recommends administration of plasma in moderate- to high-risk procedures when INR
      is >1.5. We recommend platelet transfusion in low-risk procedures when platelet
      count is <20,000/MUL, for average-risk procedures when platelet count is
      <50,000/MUL, and for procedures involving the central nervous system when the
      platelet count is <100,000/MUL.

PMID- 24124071
TI  - A dication cross-linked composite anion-exchange membrane for all-vanadium flow
      battery applications.
AB  - We report the fabrication and properties of a high-performance, inexpensive,
      composite, anion-exchange membrane (AEM) for an all-vanadium flow battery (VFB)
      application. The AEM was fabricated by dication cross-linking without the
      involvement of trimethylamine, and shows well-balanced anion conductivity and
      robustness due to imidazolium and imidazolium-ammonium functionalities, as well
      as a concomitantly achieved semi-interpenetrating network structure. The VFB
      single cell yielded a Coulombic efficiency of 99 % and an energy efficiency of 84
      % at 80 mA cm(-2) , and operated for over 900 charge/discharge cycles. This work
      demonstrates the combined use of several favorable AEM design rationales, such as
      incorporating abundant and efficient anion-exchange groups, constructing a
      swelling- and oxidation-resistant structure, and facile fabrication; it provides
      an effective way of developing high-performance, low-cost AEMs for VFB
      applications. 

PMID- 24124072
TI  - From "truly naive" to "exhausted senescent" T cells: when markers predict
      functionality.
AB  - The study of T cell biology has been accelerated by substantial progress at the
      technological level, particularly through the continuing advancement of flow
      cytometry. The conventional approach of observing T cells as either T helper or T
      cytotoxic is overly simplistic and does not allow investigators to clearly
      identify immune mechanisms or alterations in physiological processes that impact
      on clinical outcomes. The complexity of T cell sub-populations, as we understand
      them today, combined with the immunological and functional diversity of these
      subsets represent significant complications for the study of T cell biology. In
      this article, we review the use of classical markers in delineating T cell sub
      populations, from "truly naive" T cells (recent thymic emigrants with no
      proliferative history) to "exhausted senescent" T cells (poorly proliferative
      cells that display severe functional abnormalities) wherein the different
      phenotypes of these populations reflect their disparate functionalities. In
      addition, since persistent infections and chronological aging have been shown to
      be associated with significant alterations in human T cell distribution and
      function, we also discuss age-associated and cytomegalovirus-driven alterations
      in the expression of key subset markers.

PMID- 24124073
TI  - Clinical manifestations of Adult-onset Still's disease presenting with erosive
      arthritis: Association with low levels of ferritin and Interleukin-18.
AB  - Objective: Adult-onset Still's disease (AOSD) is a clinical entity with
      heterogeneous etiology. We have encountered patients with AOSD who had severe
      polyarthritis and who fulfilled the classification criteria for rheumatoid
      arthritis (RA); however, most patients with AOSD typically exhibit mild
      arthritis. In this study, we proposed two clinical subsets of AOSD and
      investigated the clinically significant characteristics of the two subtypes.
      Methods: We retrospectively analyzed 71 consecutive patients with AOSD. We
      reviewed the medical records of all patients who were followed up for more than 2
      years. We classified all the patients with AOSD into the following 2 subsets: an
      RA subtype for patients who met the criteria for RA according to the American
      College of Rheumatology and a non-RA subtype for patients who did not meet the
      criteria for RA. Results: Our results indicated that the non-RA subtype was
      accompanied by severe inflammatory complications, including pleuritis and
      hemophagocytic syndrome. In addition, the serum ferritin and serum IL-18 levels
      were significantly higher in patients with the non-RA subtype than in those with
      the RA subtype. Interestingly, only 1 patient with the RA subtype had anti-CCP
      antibodies, and 1 non-RA subtype patient had rheumatoid factor. These findings
      distinguish these patients from patients with true RA. Conclusions: There were
      two subsets of patients with AOSD in the examined population. Patients with high
      levels of IL-18 or ferritin presented with severe systemic inflammatory disorders
      (the non-RA subtype), and patients with low levels of IL-18 or ferritin developed
      severe arthritis (RA subtype).

PMID- 24124074
TI  - Classification of functioning and impairment: the development of ICF core sets
      for autism spectrum disorder.
AB  - Given the variability seen in Autism Spectrum Disorder (ASD), accurate
      quantification of functioning is vital to studying outcome and quality of life in
      affected individuals. The International Classification of Functioning, Disability
      and Health (ICF) provides a comprehensive, universally accepted framework for the
      description of health-related functioning. ICF Core Sets are shortlists of ICF
      categories that are selected to capture those aspects of functioning that are
      most relevant when describing a person with a specific condition. In this paper,
      the authors preview the process for developing ICF Core Sets for ASD, a
      collaboration with the World Health Organization and the ICF Research Branch. The
      ICF Children and Youth version (ICF-CY) was derived from the ICF and designed to
      capture the specific situation of the developing child. As ASD affects
      individuals throughout the life span, and the ICF-CY includes all ICF categories,
      the ICF-CY will be used in this project ("ICF(-CY)" from now on). The ICF(-CY)
      categories to be included in the ICF Core Sets for ASD will be determined at an
      ICF Core Set Consensus Conference, where evidence from four preparatory studies
      (a systematic review, an expert survey, a patient and caregiver qualitative
      study, and a clinical cross-sectional study) will be integrated. Comprehensive
      and Brief ICF Core Sets for ASD will be developed with the goal of providing
      useful standards for research and clinical practice and generating a common
      language for functioning and impairment in ASD in different areas of life and
      across the life span.

PMID- 24124075
TI  - Biological behavior of neurally differentiated periodontal ligament stem cells on
      different titanium implant surfaces.
AB  - We investigated the biological behavior of periodontal ligament stem cells
      (PDLSCs) induced to differentiate into Schwann cells (SCs) on the surfaces of
      titanium discs. Two types of titanium surfaces, sand blasted and acid etched (SA)
      and smooth polished, were prepared on titanium discs, and the behavior of SC-like
      cells on these discs was investigated. Cell morphology was examined by scanning
      electron microscopy, and cell proliferation was assessed using assays for
      methylthiazol tetrazolium metabolism and total protein content. Real-time
      polymerase chain reaction and Western blotting analyses were used to determine
      the gene and protein expression, respectively, of SC markers by PDLSCs.
      Differentiated PDLSCs could adhere, proliferate, differentiate, and express SC
      marker genes and proteins on the prepared titanium surfaces, and the highest
      levels of SC marker protein expression were observed in PDLSCs on SA titanium
      surfaces. SA titanium surfaces show good biocompatibility for the SC-like cells,
      which is important for the application of these cells in peri-implant nerve
      tissue engineering, through which they are expected to improve the
      osseoperception of dental implants.

PMID- 24124077
TI  - Pediatric to adult-care transitions in childhood-onset chronic disease:
      hospitalist perspectives.
AB  - OBJECTIVE: Survey of adult-centered hospitalist perspectives on caring for adults
      with chronic diseases of childhood onset (CDoCO) to investigate comfort level and
      identify targets of future educational and policy intervention. METHODS: We
      developed an on-line survey for adult-centered hospitalists based on a prior
      outpatient survey and introduced it to the Society of Hospital Medicine
      membership via e-mail. Consent was implied by completing the survey. RESULTS: Of
      all respondents, 60% saw 5 or more adults with CDoCO over a 6-month period. Among
      internal medicine respondents, 40% did not feel comfortable caring for this
      population, with lack of familiarity with the literature, lack of training in
      CDoCO, coordinating with multiple specialists, and lack of training in adolescent
      development and behavior ranked as the most significant barriers to care.
      CONCLUSION: The steadily growing population of adults with CDoCO and their high
      inpatient utilization have lead to increased care by adult-centered hospitalists,
      many of whom do not feel comfortable caring for them. Educational initiatives
      aimed at increasing medical knowledge base for common issues, training in
      adolescent development, increased care coordination, and access to address
      psychosocial issues would improve hospitalist comfort and patient care for this
      vulnerable population.

PMID- 24124076
TI  - Ribonuclease III mechanisms of double-stranded RNA cleavage.
AB  - Double-stranded(ds) RNA has diverse roles in gene expression and regulation, host
      defense, and genome surveillance in bacterial and eukaryotic cells. A central
      aspect of dsRNA function is its selective recognition and cleavage by members of
      the ribonuclease III (RNase III) family of divalent-metal-ion-dependent
      phosphodiesterases. The processing of dsRNA by RNase III family members is an
      essential step in the maturation and decay of coding and noncoding RNAs,
      including miRNAs and siRNAs. RNase III, as first purified from Escherichia coli,
      has served as a biochemically well-characterized prototype, and other bacterial
      orthologs provided the first structural information. RNase III family members
      share a unique fold (RNase III domain) that can dimerize to form a structure that
      binds dsRNA and cleaves phosphodiesters on each strand, providing the
      characteristic 2 nt, 3'-overhang product ends. Ongoing studies are uncovering the
      functions of additional domains, including, inter alia, the dsRNA-binding and PAZ
      domains that cooperate with the RNase III domain to select target sites, regulate
      activity, confer processivity, and support the recognition of structurally
      diverse substrates. RNase III enzymes function in multicomponent assemblies that
      are regulated by diverse inputs, and at least one RNase III-related polypeptide
      can function as a noncatalytic, dsRNA-binding protein. This review summarizes the
      current knowledge of the mechanisms of catalysis and target site selection of
      RNase III family members, and also addresses less well understood aspects of
      these enzymes and their interactions with dsRNA.

PMID- 24124078
TI  - Obesity bias in training: attitudes, beliefs, and observations among advanced
      trainees in professional health disciplines.
AB  - OBJECTIVE: This study examined weight bias among students training in health
      disciplines and its associations with their perceptions about treating patients
      with obesity, causes of obesity, and observations of weight bias by instructors
      and peers. METHODS: Students (N = 107) enrolled in a post-graduate health
      discipline (Physician Associate, Clinical Psychology, Psychiatric Residency)
      completed anonymous questionnaires to assess the above variables. RESULTS:
      Students reported that patients with obesity are a common target of negative
      attitudes and derogatory humor by peers (63%), health-care providers (65%), and
      instructors (40%). Although 80% of students felt confident to treat obesity, many
      reported that patients with obesity lack motivation to make changes (33%), lead
      to feelings of frustration (36%), and are non-compliant with treatment (36%).
      Students with higher weight bias expressed greater frustration in these areas.
      The effect of students' weight bias on expectations for treatment compliance of
      patients with obesity was partially mediated by beliefs that obesity is caused by
      behavioral factors. CONCLUSIONS: Weight bias is commonly observed by students in
      health disciplines, who themselves report frustrations and stereotypes about
      treating patients with obesity. These findings contribute new knowledge about
      weight bias among students and provide several targets for medical training and
      education.

PMID- 24124079
TI  - Pretreatment of sinus aspirates with dithiothreitol improves yield of fungal
      cultures in patients with chronic sinusitis.
AB  - BACKGROUND: Mold pathogens are a leading cause of chronic rhinosinusitis.
      Successful isolation of mold on culture is helpful in establishing a diagnosis
      and guiding therapy. Though mucolytic agents are commonly used in European
      countries, they are not part of everyday use in North America. In this case
      control prospective study, we investigated the yield of fungal culture before and
      after treatment of sinus aspirates with the mucolytic agent dithiothreitol in a
      United States hospital. METHODS: Over a 5-month period during 2011-2012, 359
      sinus aspirates from 294 patients with symptoms suspicious for chronic sinusitis
      or allergic fungal sinusitis were collected. Aspirates were cultured on fungal
      medium before and after treatment with dithiothreitol. RESULTS: Of the 359 pairs
      of cultures, 62 (17.3%) demonstrated mold growth on at least 1 of the plates, 9
      (14.5%) of which grew more than 1 species of mold. A total of 75 molds were
      identified, 41 (54.7%) of which were successfully cultured only when the mucus
      was pretreated with dithiothreitol (p < 0.0001). Quantitatively, more colonies
      grew from dithiothreitol-treated mucus than from direct-inoculation (p < 0.0001).
      CONCLUSION: This study confirms improved recovery of mold from sinus cultures
      after pretreatment of samples with dithiothreitol. Further studies are needed to
      correlate these findings with clinical outcome.

PMID- 24124080
TI  - Screening of testosterone esters in human plasma.
AB  - The detection of an intact ester of testosterone in plasma is leading towards
      unequivocal proof of the administration of exogenous testosterone. In the current
      study, a sensitive screening method for the detection of nine testosterone esters
      in human plasma was developed. By preparing oxime derivatives of intact
      testosterone esters, the sensitivity of the assay was increased. Furthermore, the
      method included liquid-liquid extraction (LLE) as sample clean-up, as well as
      online separation of the target analytes from the derivatization solution. The
      analysis was performed by liquid chromatography (LC) coupled to tandem mass
      spectrometry (MS/MS). The method developed herein is simple and rapid, and was
      validated according to World Anti-Doping Agency (WADA) guidelines.

PMID- 24124081
TI  - GH Therapy and first final height data in Noonan-like syndrome with loose anagen
      hair (Mazzanti syndrome).
AB  - Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is
      caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the
      encoded protein. Cardinal features include facial features resembling NS, short
      stature often associated with proven growth hormone deficiency (GHD), typical
      ectodermal anomalies, and distinctive behavior. Overall, the clinical features
      are more severe than those generally observed in NS, even though the phenotype
      improves with age. We report on growth and pubertal trend in seven patients
      heterozygous for a mutated SHOC2 allele, treated with long-term GH-therapy, and
      final height (FH) in three of them. They were approximately -3 SDS below the
      Italian general population standards, they had very low IGF1 levels at baseline
      and GHD at pharmacological tests. All patients were treated with GH (0.035
      mg/kg/day) for a mean period of 8.49 +/- 5.72 years. After the 1st year of GH
      therapy, IGF1 level and height velocity had increased. Three of 7 patients
      reached the FH (-2.34 +/- 0.12 SDS) at 18.25 +/- 0.73 years, after GH
      administration for 12.39 +/- 2.12 years. Pubertal development was variable,
      showing a prolonged and delayed puberty or rapid pubertal progression that could
      impair the FH. Overall, our data in this small cohort suggest that NS/LAH
      patients benefit from long-term GH-therapy, although they do not show the
      characteristic catch-up growth of isolated GHD. While the observed growth and
      pubertal behavior is consistent with a dysfunction of the hypothalamic-pituitary
      gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways
      remains to be clarified.

PMID- 24124082
TI  - An assay for the bacterial sweet spot.

PMID- 24124083
TI  - MALDI-TOF characterization of hGH1 produced by hairy root cultures of Brassica
      oleracea var. italica grown in an airlift with mesh bioreactor.
AB  - Expression systems based on plant cells, tissue, and organ cultures have been
      investigated as an alternative for production of human therapeutic proteins in
      bioreactors. In this work, hairy root cultures of Brassica oleracea var. italica
      (broccoli) were established in an airlift with mesh bioreactor to produce isoform
      1 of the human growth hormone (hGH1) as a model therapeutic protein. The hGH1
      cDNA was cloned into the pCAMBIA1105.1 binary vector to induce hairy roots in
      hypocotyls of broccoli plantlets via Agrobacterium rhizogenes. Most of the
      infected plantlets (90%) developed hairy roots when inoculated before the
      appearance of true leaves, and keeping the emerging roots attached to hypocotyl
      explants during transfer to solid Schenk and Hildebrandt medium. The
      incorporation of the cDNA into the hairy root genome was confirmed by PCR
      amplification from genomic DNA. The expression and structure of the transgenic
      hGH1 was assessed by ELISA, western blot, and MALDITOF-MS analysis of the
      purified protein extracted from the biomass of hairy roots cultivated in
      bioreactor for 24 days. Production of hGH1 was 5.1 +/- 0.42 ug/g dry weight (DW)
      for flask cultures, and 7.8 +/- 0.3 ug/g DW for bioreactor, with productivity of
      0.68 +/- 0.05 and 1.5 +/- 0.06 ug/g DW*days, respectively, indicating that the
      production of hGH1 was not affected by the growth rate, but might be affected by
      the culture system. These results demonstrate that hairy root cultures of
      broccoli have potential as an alternative expression system for production of
      hGH1, and might also be useful for production of other therapeutic proteins.

PMID- 24124084
TI  - A self-healing biomaterial based on free-radical polymerization.
AB  - Self-healing chemistry used for damage repair have not previously been
      demonstrated for free-radical polymerization pathways. However, this chemistry is
      important for addition polymers such as poly(methyl methacrylate) used in bone
      cement and epoxy vinyl ester used in dental resins. Self-healing biomaterials
      offer the potential for safer and longer lasting implants and restoratives by
      slowing or arresting crack damage. In the free-radical self-healing system
      reported here, the three components required for polymerization (free-radical
      peroxide initiator, tertiary amine activator, and vinyl acrylate monomers) are
      compartmentalized into two separate microcapsules-one containing the peroxide
      initiator, and the other containing both monomer and activator. Crack damage
      ruptures the capsules so that the three components mix and react to form a new
      polymer that effectively rebonds the crack and restores approximately 75% of the
      original fracture toughness. Optimal healing is obtained by a systematic
      evaluation of the effect of monomer, initiator, and activator concentration on
      healing performance.

PMID- 24124085
TI  - Genetic sequence analysis of inherited bleeding diseases.
AB  - The genes encoding the coagulation factor proteins were among the first human
      genes to be characterized over 25 years ago. Since then, significant progress has
      been made in the translational application of this information for the 2
      commonest severe inherited bleeding disorders, hemophilia A and B. For these X
      linked disorders, genetic characterization of the disease-causing mutations is
      now incorporated into the standard of care and genetic information is used for
      risk stratification of treatment complications. With electronic databases
      detailing >2100 unique mutations for hemophilia A and >1100 mutations for
      hemophilia B, these diseases are among the most extensively characterized
      inherited diseases in humans. Experience with the genetics of the rare bleeding
      disorders is, as expected, less well advanced. However, here again, electronic
      mutation databases have been developed and provide excellent guidance for the
      application of genetic analysis as a confirmatory approach to diagnosis. Most
      recently, progress has also been made in identifying the mutant loci in a variety
      of inherited platelet disorders, and these findings are beginning to be applied
      to the genetic diagnosis of these conditions. Investigation of patients with
      bleeding phenotypes without a diagnosis, using genome-wide strategies, may
      identify novel genes not previously recognized as playing a role in hemostasis. 

PMID- 24124086
TI  - Rituximab maintenance after first-line therapy with rituximab, fludarabine,
      cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia.
AB  - The effectiveness of rituximab maintenance therapy in the treatment of chronic
      lymphocytic leukemia has been investigated in a phase 2 clinical trial that
      included an initial treatment with rituximab 500 mg/m2 on day 1 (375 mg/m2 the
      first cycle), fludarabine 25 mg/m2 on days 1 to 3, cyclophosphamide 200 mg/m2 on
      days 1 to 3, and mitoxantrone 6 mg/m2 on day 1 (R-FCM), for 6 cycles, followed by
      a maintenance phase with rituximab 375 mg/m2 every 3 months for 2 years. Sixty
      seven patients having achieved complete response (CR) or partial response (PR)
      with R-FCM were given maintenance therapy. At the end of maintenance, 40.6% of
      patients were in CR with negative minimal residual disease (MRD), 40.6% were in
      CR MRD-positive, 4.8% remained in PR, and 14% were considered failures. Six of 29
      patients (21%) who were in CR MRD-positive or in PR after R-FCM improved their
      response upon rituximab maintenance. The 4-year progression-free survival (PFS)
      and overall survival rates were 74.8% and 93.7%, respectively. MRD status after R
      FCM induction was the strongest predictor of PFS. Maintenance with rituximab
      after R-FCM improved the quality of the response, particularly in patients MRD
      positive after initial treatment, and obtained a prolonged PFS. This trial was
      registered at www.clinicaltrialsregister.eu as identifier #2005-001569-33. 

PMID- 24124088
TI  - Pivotal role of Pten in the balance between proliferation and differentiation of
      hematopoietic stem cells in zebrafish.
AB  - Self-renewing hematopoietic stem/progenitor cells (HSPCs) produce blood cells of
      all lineages throughout life. Phosphatase and tensin homolog (PTEN), a tumor
      suppressor that antagonizes phosphatidylinositol 3-kinase (PI3K) signaling, is
      frequently mutated in hematologic malignancies such as bone marrow failure and
      leukemia. We set out to investigate whether Pten is required for hematopoiesis.
      Analysis of zebrafish mutants lacking functional Pten revealed that HSPCs
      colonized the caudal hematopoietic tissue normally. There, HSPCs
      hyperproliferated and engaged in all blood lineages. However, they failed to
      differentiate into mature blood cells. Hence, Pten mutant zebrafish embryos
      displayed hallmarks of leukemia in humans. Inhibition of PI3K signaling in
      mutants lacking functional Pten suppressed hyperproliferation and released the
      differentiation arrest. We conclude that Pten has an essential role in the
      balance between proliferation and differentiation of blood cells. 

PMID- 24124089
TI  - Value of contrast-enhanced ultrasonography for the detection and quantification
      of enthesitis vascularization in patients with spondyloarthritis.
AB  - OBJECTIVE: To evaluate if contrast-enhanced ultrasound (CEUS) can improve the
      detection and quantification of the vascularization of mild enthesitis in
      spondyloarthritis (SpA) and to evaluate the influence of nonsteroidal
      antiinflammatory drugs (NSAIDs) on such detection. METHODS: Fourteen patients
      with mildly active SpA were evaluated at 3 consecutive visits: at baseline while
      undergoing NSAID treatment (V1), after 1 week of stopping NSAIDs (V2), and after
      1 week of resuming NSAIDs (V3). At each visit, enthesitis was evaluated
      clinically and by power Doppler US (PDUS). A selected enthesis with a doubtful
      PDUS vascularization signal was studied by CEUS in 2 steps: (1) using a dedicated
      technology that preserves microbubbles (Contrast Tuned Imaging technology [CEUS
      CnTI]) and (2) using high PD (CEUS-PD) to destroy microbubbles. A linear mixed
      model statistical analysis, taking visits and contrast agent as fixed factors and
      the patient as a random factor, was used. RESULTS: Disease activity and PDUS
      findings increased between V1 and V2 and then decreased between V2 and V3. As
      compared with PDUS alone, CEUS-PD and CEUS-CnTI each detected 1 supplementary
      vascularized enthesis at V1, CEUS-PD detected 1 vascularized enthesis and CEUS
      CnTI detected 3 vascularized entheses at V2, and CEUS-PD and CEUS-CnTI each
      detected 2 vascularized entheses at V3. The mean inflammation score was increased
      by the use of CEUS (P = 0.04). This score increased between V1 and V2 (P = 0.03
      by CEUS-PD and P = 0.01 by CEUS-CnTI) and decreased between V2 and V3.
      CONCLUSION: CEUS improved the detection of enthesitis in SpA patients by
      confirming all doubtful enthesitis signals and confirming the absence of enthesis
      vascularization. The use of NSAIDs influenced the detection of vascularization.

PMID- 24124087
TI  - Hematopoietic specification from human pluripotent stem cells: current advances
      and challenges toward de novo generation of hematopoietic stem cells.
AB  - Significant advances in cellular reprogramming technologies and hematopoietic
      differentiation from human pluripotent stem cells (hPSCs) have already enabled
      the routine production of multiple lineages of blood cells in vitro and opened
      novel opportunities to study hematopoietic development, model genetic blood
      diseases, and manufacture immunologically matched cells for transfusion and
      cancer immunotherapy. However, the generation of hematopoietic cells with robust
      and sustained multilineage engraftment has not been achieved. Here, we highlight
      the recent advances in understanding the molecular and cellular pathways leading
      to blood development from hPSCs and discuss potential approaches that can be
      taken to facilitate the development of technologies for de novo production of
      hematopoietic stem cells. 

PMID- 24124090
TI  - A method for creating microporous carbon materials with excellent CO2-adsorption
      capacity and selectivity.
AB  - A new synthetic approach for the fabrication of microporous carbon materials
      (HCMs) by using discrete chelating zinc species as dynamic molecular porogens to
      create extra micropores that enhance their CO2-adsorption capacity and
      selectivity is reported. During the carbonization process, the evaporation of the
      in situ-formed Zn species would create additional nanochannels that contribute to
      the additional micropore volume for CO2 adsorption. The resultant HCMs show an
      increased number of micropores, with sizes in the range 0.7-1.0 nm and a high CO2
      -adsorption capacity of 5.4 mmol g(-1) (23.8 wt%) at 273 K and 3.8 mmol g(-1)
      (16.7 wt%) at 298 K and 1 bar, which are superior to those of most carbon-based
      adsorbents with N-doping or high specific surface areas. Dynamic gas-separation
      measurements, by using 16% CO2 in N2 (v/v) as a feedstock, demonstrated that CO2
      could be effectively separated from N2 under ambient conditions and shows a high
      separation factor (S(CO2)/N2=110) for CO2 over N2, thereby reflecting a strongly
      competitive CO2 -adsorption capacity. If the feedstock contained water vapor, the
      dynamic capacity of CO2 was almost identical to that measured under dry
      conditions, thus indicating that the carbon material had excellent tolerance to
      humidity. Easy CO2 release could be realized by purging an argon flow through the
      fixed-bed adsorber at 298 K, thus indicating good regeneration ability.

PMID- 24124092
TI  - A methamphetamine analog (N,alpha-diethyl-phenylethylamine) identified in a
      mainstream dietary supplement.
AB  - Pharmaceuticals and banned substances have been detected in hundreds of
      purportedly natural supplements. Recently, several athletes have been
      disqualified from competition after testing positive for the methamphetamine
      analog N,alpha-diethyl-phenylethylamine (N,alpha-DEPEA). Athletes have claimed
      they unknowingly consumed the banned stimulant in workout supplements. Three
      samples from different lot numbers of Craze, a workout supplement, were analyzed
      to detect the presence and concentration of N,alpha-DEPEA. Two labs independently
      identified N,alpha-DEPEA in the supplement using ultra high performance liquid
      chromatography (UHPLC) coupled to an LTQ Orbitrap XL mass spectrometer and UHPLC
      quadruple-time-of-flight mass (Q-TOF) spectrometer, respectively. The identity of
      N,alpha-DEPEA was confirmed using nuclear magnetic resonance and reference
      standards. Manufacturer recommended servings were estimated to provide 21 to 35
      mg of N,alpha-DEPEA. N,alpha-DEPEA has never been studied in humans. N,alpha
      DEPEA is a methamphetamine analog; however, its stimulant, addictive and other
      adverse effects in humans are entirely unknown. Regulatory agencies should act
      expeditiously to warn consumers and remove N,alpha-DEPEA from all dietary
      supplements.

PMID- 24124093
TI  - Self-rated social skills predict visual perception: impairments in object
      discrimination requiring transient attention associated with high autistic
      tendency.
AB  - Autism is usually defined by impairments in the social domain but has also been
      linked to deficient dorsal visual stream processing. However, inconsistent
      findings make the nature of this relationship unclear and thus, we examined the
      role of stimulus-driven transient attention, presumably activated by the dorsal
      stream in autistic tendency. Contrast thresholds for object discrimination were
      compared between groups with high and low self-rated autistic tendency utilizing
      the socially based Autism Spectrum Quotient (AQ). Visual stimuli were presented
      with either abrupt or with ramped contrast onsets/offsets in order to manipulate
      the demands of transient attention. Larger impairments in performance of abrupt
      compared with ramped object presentation were established in the high AQ group.
      Furthermore, self-reported social skills predicted abrupt task performance,
      suggesting an important visual perception deficiency in autism-related traits.
      Autism spectrum disorder may be associated with reduced utilization of the dorsal
      stream to rapidly activate attention prior to ventral stream processing when
      stimuli are transient.

PMID- 24124094
TI  - Do internal medicine interns practice etiquette-based communication? A critical
      look at the inpatient encounter.
AB  - Etiquette-based communication may improve the inpatient experience but is not
      universally practiced. We sought to determine the extent to which internal
      medicine interns practice behaviors that characterize etiquette-based medicine.
      Trained observers evaluated the use of 5 key communication strategies by internal
      medicine interns during inpatient clinical encounters: introducing one's self,
      explaining one's role in the patient's care, touching the patient, asking open
      ended questions, and sitting down with the patient. Participants at 1 site then
      completed a survey estimating how frequently they performed each of the observed
      behaviors. A convenience sample of 29 interns was observed on a total of 732
      patient encounters. Overall, interns introduced themselves 40% of the time and
      explained their role 37% of the time. Interns touched patients on 65% of visits,
      asked open-ended questions on 75% of visits, and sat down with patients during 9%
      of visits. Interns at 1 site estimated introducing themselves and their role and
      sitting with patients significantly more frequently than was observed (80% vs
      40%, P < 0.01; 80% vs 37%, P < 0.01; and 58% vs 9%, P < 0.01, respectively).
      Resident physicians introduced themselves to patients, explained their role, and
      sat down with patients infrequently during observed inpatient encounters.
      Residents surveyed tended to overestimate their own practice of etiquette-based
      medicine.

PMID- 24124095
TI  - Tetrahydroisoquinolinone-based steroidomimetic and chimeric microtubule
      disruptors.
AB  - A structure-activity relationship (SAR) translation strategy was used for the
      discovery of tetrahydroisoquinoline (THIQ)-based steroidomimetic and chimeric
      microtubule disruptors based upon a steroidal starting point. A steroid A,B-ring
      mimicking THIQ core was connected to methoxyaryl D-ring ring mimics through
      methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic
      hits (e.g., 7-methoxy-2-(3- methoxybenzyl)-6-sulfamoyloxy-1,2,3,4
      tetrahydroisoquinoline (20 c) GI50=2.1 MUM). Optimisation and control experiments
      demonstrate the complementary SAR of this series and the steroid derivatives that
      inspired its design. Linkage of the THIQ-based A,B-mimic with the trimethoxyaryl
      motif prevalent in colchicine site binding microtubule disruptors delivered a
      series of chimeric molecules whose activity (GI50=40 nM) surpasses that of the
      parent steroid derivatives. Validation of this strategy was obtained from the
      excellent oral activity of 7-methoxy-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)
      1,2,3,4-tetrahydroisoquinoline relative to a benchmark steroidal bis- sulfamate
      in an in vivo model of multiple myeloma.

PMID- 24124097
TI  - Spatiotemporal cytometry-simultaneous analysis of DNA replication and damage.

PMID- 24124098
TI  - Hyaluronic acid-based nanocomposite hydrogels for ocular drug delivery
      applications.
AB  - Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic
      applications owing to its unique properties of biocompatibility, biodegradation,
      and viscoelasticity. HA being a natural component of eye tissue with significant
      role in wound healing is a natural choice as a carrier for ocular drug delivery,
      provided the incorporated drugs are released in a sustained manner. However,
      localized sustained release of drugs inside eye has been difficult to achieve
      because of the inability to retain carriers for long periods in the eye. Using
      noncrosslinked (soluble) HA offers limited control over site retention of drugs.
      In order to obtain prolonged sustained delivery, two HA-based composite hydrogels
      incorporating nanocarriers, have been synthesized and characterized for swelling,
      rheology, degradation, and in vitro release of latanoprost, a drug used to reduce
      intraocular pressure. The HA is first chemically modified, mixed with drug-loaded
      liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro
      release study shows longer sustained release of latanoprost from composite
      hydrogels as compared to liposomes or hydrogels alone indicating additional
      resistance to drug diffusion because of the incorporation of liposomes inside the
      hydrogels. It is believed that these nanocomposite hydrogels, with controlled
      degradation properties and sustained release, could serve as potential drug
      delivery systems for many ocular diseases.

PMID- 24124096
TI  - Recognition modes of RNA tetraloops and tetraloop-like motifs by RNA-binding
      proteins.
AB  - RNA hairpins are the most commonly occurring secondary structural elements in
      RNAs and serve as nucleation sites for RNA folding, RNA-RNA, and RNA-protein
      interactions. RNA hairpins are frequently capped by tetraloops, and based on
      sequence similarity, three broad classes of RNA tetraloops have been defined:
      GNRA, UNCG, and CUYG. Other classes such as the UYUN tetraloop in histone mRNAs,
      the UGAA in 16S rRNA, the AUUA tetraloop from the MS2 bacteriophage, and the AGNN
      tetraloop that binds RNase III have also been characterized. The tetraloop
      structure is compact and is usually characterized by a paired interaction between
      the first and fourth nucleotides. The two unpaired nucleotides in the loop are
      usually involved in base-stacking or base-phosphate hydrogen bonding
      interactions. Several structures of RNA tetraloops, free and complexed to other
      RNAs or proteins, are now available and these studies have increased our
      understanding of the diverse mechanisms by which this motif is recognized. RNA
      tetraloops can mediate RNA-RNA contacts via the tetraloop-receptor motif, kissing
      hairpin loops, A-minor interactions, and pseudoknots. While these RNA-RNA
      interactions are fairly well understood, how RNA-binding proteins recognize RNA
      tetraloops and tetraloop-like motifs remains unclear. In this review, we
      summarize the structures of RNA tetraloop-protein complexes and the general
      themes that have emerged on sequence- and structure-specific recognition of RNA
      tetraloops. We highlight how proteins achieve molecular recognition of this
      nucleic acid motif, the structural adaptations observed in the tetraloop to
      accommodate the protein-binding partner, and the role of dynamics in recognition.

PMID- 24124099
TI  - Endoscopic orbital floor decompression with preservation of the inferomedial
      strut.
AB  - BACKGROUND: Medial and inferior orbital decompression is most commonly performed
      in the setting of dysthyroid orbitopathy. Diplopia represents the most common
      complication and may be minimized through the preservation of a bony inferomedial
      strut (IMS). Historically, this has required a transconjunctival approach due to
      the technical demands of performing an isolated orbital floor decompression using
      endoscopic instrumentation. Here we describe a novel technique of a purely
      endoscopic orbital floor decompression with reliable preservation of the IMS.
      METHODS: Description of a novel surgical technique for endoscopic orbital floor
      decompression with IMS preservation using frontal sinus instrumentation
      visualized by a 70-degree endoscope. RESULTS: We have successfully used this
      technique in 12 orbits with 100% preservation of the bony inferomedial strut and
      no complications. The extent of decompression and width of the residual strut may
      be fine tuned as needed to optimize results. CONCLUSION: Orbital floor
      decompression with IMS preservation may be reliably performed using purely
      endoscopic techniques. Successful completion of this procedure requires the
      adaptation of standard frontal sinus instrumentation to the maxillary sinus roof
      and thus may be readily mastered by any endoscopic surgeon comfortable with
      frontal sinus techniques.

PMID- 24124100
TI  - Noble-metal-free NiS/C3 N4 for efficient photocatalytic hydrogen evolution from
      water.
AB  - A NiS/C3 N4 photocatalyst containing earth-abundant elements only was constructed
      by means of a simple hydrothermal method. This photocatalyst shows efficient
      hydrogen evolution (48.2 MUmol h(-1) ) under visible light when using
      triethanolamine as a sacrificial reagent. The optimal loading of 1.1 wt % NiS on
      C3 N4 as a cocatalyst can enhance the H2 production by about 250 times compared
      with the native C3 N4 . The highest apparent quantum efficiency of 1.9 % was
      recorded at 440 nm. 

PMID- 24124101
TI  - Science, art, and mistery in the statues and in the anatomical machines of the
      prince of sansevero: the masterpieces of the "Sansevero Chapel".
AB  - During the 18th century in Naples, Raimondo di Sangro, Prince of Sansevero,
      completed works on the family chapel, the so-called "Cappella Sansevero." The
      chapel houses statues of extraordinary beauty and spectacularly detailed but
      also, in the basement, two human skeletons known as the "Anatomical Machines"
      ("Macchine Anatomiche"). These two skeletons, a man and a pregnant woman, are
      entirely surrounded by their circulatory systems, just as if these were suddenly
      fixed. Legend, believed as truth until few years ago, says that Prince Raimondo
      had prepared and injected an unknown embalming substance in the blood vessels of
      two of his servants convicting them to eternal fixity. Recent investigations have
      demonstrated that, while the bones are authentic, the blood vessels are actually
      extraordinary artifacts that also reproduce some congenital malformations. The
      dreadful aspect of these two skeletons appears to be in strident contrast with
      the classic beauty of the statues which glorify and celebrate the ideal of
      morphology. Conversely, the two Anatomical Machines, protagonists of legends and
      superstitions since centuries, represent a marvelous example of science mixed
      with art.

PMID- 24124102
TI  - Lower NLRP3 inflammasome activity in NAG-1 transgenic mice is linked to a
      resistance to obesity and increased insulin sensitivity.
AB  - OBJECTIVE: The NLRP3 inflammasome plays an important regulatory role in obesity
      induced insulin resistance. NSAID activated gene-1 (NAG-1) is a divergent member
      of the TGF-beta superfamily. NAG-1 Tg mice are resistant to dietary- and genetic
      induced obesity and have improved insulin sensitivity. The objective was to
      examine whether NLRP3 inflammasome activity is associated with this observed
      phenotype in NAG-1 Tg mice. METHODS: Key components of the NLRP3 inflammasome
      were examined in NAG-1 Tg mice on both regular and high fat diet (HFD)
      conditions. RESULTS: The expression of caspase-1 and ASC, key components of the
      NLRP3 inflammasome, is significantly reduced at mRNA and protein levels in white
      adipose tissue (WAT) of NAG-1 Tg mice. HFD increases the expression of caspase-1
      and ASC in WT mice, but their expression is reduced in NAG-1 Tg mice.
      Furthermore, there is reduced IL-18, IL-1beta, and TNF-alpha expression in the
      WAT of NAG-1 Tg mice. NAG-1 Tg mice have significantly lower serum leptin and
      insulin levels and reduced expression of macrophage infiltration markers (F4/80,
      CD11b, and CD11c) in WAT. CONCLUSIONS: The study suggests the lower NLRP3
      inflammasome activity may play a role in the resistance of NAG-1 Tg mice to diet
      induced obesity and improved insulin sensitivity.

PMID- 24124103
TI  - Screening strategy of depression in patients with systemic sclerosis with special
      reference to suicide: comment on the article by Razykov et al.

PMID- 24124106
TI  - De novo design, synthesis and evaluation of benzylpiperazine derivatives as
      highly selective binders of Mcl-1.
AB  - Considerable efforts have been made to the development of small-molecule
      inhibitors of antiapoptotic B-cell lymphoma 2 (Bcl-2) family proteins (such as
      Bcl-2, Bcl-xL , and Mcl-1) as a new class of anticancer therapies. Unlike general
      inhibitors of the entire family, selective inhibitors of each member protein can
      hopefully reduce the adverse side effects in chemotherapy treatments of cancers
      overexpressing different Bcl-2 family proteins. In this study, we designed four
      series of benzylpiperazine derivatives as plausible Bcl-2 inhibitors based on the
      outcomes of a computational algorithm. A total of 81 compounds were synthesized,
      and their binding affinities to Bcl-2, Bcl-xL , and Mcl-1 measured.
      Encouragingly, 22 compounds exhibited binding affinities in the micromolar range
      (Ki <20 MUM) to at least one target protein. Moreover, some compounds were
      observed to be highly selective binders to Mcl-1 with no detectable binding to
      Bcl-2 or Bcl-xL , among which the most potent one has a Ki value of 0.18 MUM for
      Mcl-1. Binding modes of four selected compounds to Mcl-1 and Bcl-xL were derived
      through molecular docking and molecular dynamics simulations. It seems that the
      binding affinity and selectivity of these compounds can be reasonably interpreted
      with these models. Our study demonstrated the possibility for obtaining selective
      Mcl-1 inhibitors with relatively simple chemical scaffolds. The active compounds
      identified by us could be used as lead compounds for developing even more potent
      selective Mcl-1 inhibitors with potential pharmaceutical applications. 

PMID- 24124105
TI  - Smoking cessation treatment and risk of depression, suicide, and self harm in the
      Clinical Practice Research Datalink: prospective cohort study.
AB  - OBJECTIVE: To compare the risk of suicide, self harm, and depression in patients
      prescribed varenicline or bupropion with those prescribed nicotine replacement
      therapy. DESIGN: Prospective cohort study within the Clinical Practice Research
      Datalink. SETTING: 349 general practices in England. PARTICIPANTS: 119,546 men
      and women aged 18 years and over who used a smoking cessation product between 1
      September 2006 and 31 October 2011. There were 81,545 users of nicotine
      replacement products (68.2% of all users of smoking cessation medicines), 6741
      bupropion (5.6%), and 31,260 varenicline (26.2%) users. MAIN OUTCOME MEASURES:
      Outcomes were treated depression and fatal and non-fatal self harm within three
      months of the first smoking cessation prescription, determined from linkage with
      mortality data from the Office for National Statistics (for suicide) and Hospital
      Episode Statistics data (for hospital admissions relating to non-fatal self
      harm). Hazard ratios or risk differences were estimated using Cox multivariable
      regression models, propensity score matching, and instrumental variable analysis
      using physicians' prescribing preferences as an instrument. Sensitivity analyses
      were performed for outcomes at six and nine months. RESULTS: We detected 92 cases
      of fatal and non-fatal self harm (326.5 events per 100,000 person years) and 1094
      primary care records of treated depression (6963.3 per 100,000 person years). Cox
      regression analyses showed no evidence that patients prescribed varenicline had
      higher risks of fatal or non-fatal self harm (hazard ratio 0.88, 95% confidence
      interval 0.52 to 1.49) or treated depression (0.75, 0.65 to 0.87) compared with
      those prescribed nicotine replacement therapy. There was no evidence that
      patients prescribed bupropion had a higher risk of fatal or non-fatal self harm
      (0.83, 0.30 to 2.31) or of treated depression (0.63, 0.46 to 0.87) compared with
      patients prescribed nicotine replacement therapy. Similar findings were obtained
      using propensity score methods and instrumental variable analyses. CONCLUSIONS:
      There is no evidence of an increased risk of suicidal behaviour in patients
      prescribed varenicline or bupropion compared with those prescribed nicotine
      replacement therapy. These findings should be reassuring for users and
      prescribers of smoking cessation medicines.

PMID- 24124107
TI  - Mechanocatalytic deconstruction of cellulose: an emerging entry into biorefinery.
AB  - Deconstructing cellulose: This highlight presents an emerging concept dealing
      with the mechanocatalytic deconstruction of biopolymers including cellulose,
      lignin, and lignocellulosic biomass. This dry treatment of biomass is expected to
      open new horizons in the field of biomass processing. In particular,
      mechanocatalysis is now considered as a promising entry into biorefinery. 

PMID- 24124108
TI  - Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing
      cell proliferation and enhancing apoptosis.
AB  - SCOPE: Quercetin is the most abundant flavonoid in human diet. It has special
      interest as it holds anticancerous properties. This study aims to clarify the
      mechanisms involved in quercetin effects during the occurrence of preneoplastic
      lesions in rat liver. METHODS AND RESULTS: Adult male Wistar rats were subjected
      to a two-phase model of hepatocarcinogenesis (initiated-promoted group).
      Initiated-promoted animals also received quercetin 10 and 20 mg/kg body weight
      (IPQ10 and IPQ20 groups, respectively). Antioxidant defenses were modified by
      quercetin administration at both doses. However, only IPQ20 group showed a
      reduction in number and volume of preneoplastic lesions. This group showed
      increased apoptosis and a reduction in the proliferative index. In addition,
      IPQ20 group displayed a reduction of cell percentages in G1 and S phases,
      accumulation in G2, and decrease in M phase, with reduced expression of cyclin
      D1, cyclin A, cyclin B, and cyclin-dependent kinase 1. Interestingly, peroxisome
      proliferator activated receptor-alpha levels were reduced in IPQ20 group.
      CONCLUSION: The outcomes of this study represent a significant contribution to
      the current understanding on the preventive mechanisms of quercetin during the
      early stages of liver cancer development, demonstrating that in addition to its
      known proapoptotic characteristics, the flavonoid modulates the expression of
      critical cell cycle regulators and peroxisome proliferator activated receptor
      alpha activity.

PMID- 24124109
TI  - Competition and collaboration between RNA-binding proteins and microRNAs.
AB  - Posttranscriptional regulation of mRNA species represents a major regulatory
      checkpoint in the control of gene expression. Historically, RNA-binding proteins
      (RBPs) have been regarded as the primary regulators of mRNA stability and
      translation. More recently, however, microRNAs have emerged as a class of potent
      and pervasive posttranscriptional rheostats that similarly affect mRNA stability
      and translation. The observation that both microRNAs and RBPs regulate mRNA
      stability and translation has initiated a newer area of research that involves
      the examination of dynamic interactions between these two important classes of
      posttranscriptional regulators, the myriad of factors that influence these
      biological interactions, and ultimately, their effects on target mRNAs.
      Specifically, microRNAs and RBPs can act synergistically to effect mRNA
      destabilization and translational inhibition. They can also engage in competition
      with each other and exert opposing effects on target mRNAs. To date, several key
      studies have provided critical details regarding the mechanisms and principles of
      interaction between these molecules. Additionally, these findings raise important
      questions regarding the regulation of these interactions, including the roles of
      posttranslational modification, subcellular localization, target inhibition
      versus activation, and changes in expression levels of these regulatory factors,
      especially under stimulus- and cell-specific conditions. Indeed, further
      experimentation is warranted to address these key issues that pertain to the
      collaboration and competition between microRNAs and RBPs. Significantly, the
      elucidation of these important details bears critical implications for disease
      management, especially for those diseases in which these cellular factors are
      dysregulated.

PMID- 24124110
TI  - ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker
      for mutational status.
AB  - The strongest prognostic factor in chronic B-cell lymphocytic leukaemia (CLL) is
      the mutational status of the immunoglobulin heavy chain variable region (IGHV)
      genes. Determination of this mutational status is laborious and therefore not
      applied in routine diagnostics. A search for 'surrogate markers' has been
      conducted over the past few years. One of the most promising surrogate markers is
      ZAP70, but standardisation of the measurement of ZAP70 has proven to be
      difficult. Conventionally, ZAP70 expression in CLL cells is related to ZAP70
      expression in T cells. We propose a new method in which ZAP70 expression in NK
      cells is used as reference (new NK-MFI method). We have measured ZAP70 expression
      in samples of 45 previously untreated CLL patients. ZAP70 in CLL cells related to
      ZAP70 in NK cells correlated better to cytogenetic risk profile and mutational
      status than the conventional methods. Negativity of both ZAP70 (new NK-MFI
      method) and CD38 resulted in a probability of 90% for mutated IGHV genes. In
      conclusion, ZAP70 expression in CLL cells related to ZAP70 expression in NK cells
      is a better surrogate marker for mutational status than the conventional T cell
      related methods. (c) 2013 Clinical Cytometry Society.

PMID- 24124111
TI  - Increased prepulse inhibition and sensitization of the startle reflex in autistic
      children.
AB  - The relation between autism spectrum disorders (ASD) and schizophrenia is a
      subject of intense debate and research due to evidence of common neurobiological
      pathways in the two disorders. The objective of this study was to explore whether
      deficits in prepulse inhibition (PPI) of the startle reflex, as usually seen in
      schizophrenic patients, can be replicated in a group of children with ASD in
      comparison with a group of matched neuro-typically developed (NTD) controls. An
      additional aim was to explore possible psychophysiological subgroups within our
      ASD sample. In a case-control design, 35 ASD patients and 40 matched NTD controls
      were tested in a psychophysiological test battery. The PPI of the acoustic
      startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation
      and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials
      with less intense prestimuli (76 dB), patients with ASD did not display the drop
      in percentage PPI normally found in healthy controls. In addition, ASD patients
      showed significantly increased sensitization compared with NTD controls.
      Combined, our results may reflect the hypersensitivity to sensory information in
      children with ASD. The relation to PPI deficits observed in schizophrenia is not
      apparent. Future research should study the developmental course of PPI deficits
      in ASD patients in a longitudinal design.

PMID- 24124112
TI  - Symbiotic prokaryotic communities from different populations of the giant barrel
      sponge, Xestospongia muta.
AB  - The prokaryotic community composition of the ecologically dominant sponge,
      Xestospongia muta, and the variability of this community across in different
      populations of sponges from the Caribbean and Bahamas were quantified using 454
      pyrosequencing of the 16S rRNA gene. The symbiotic prokaryotic communities of X.
      muta were significantly different than the surrounding bacterioplankton
      communities while an analysis of similarity (ANOSIM) of the sponge prokaryotic
      symbionts from three geographically distant sites showed that both symbiont and
      bacterioplankton populations were significantly different between locations.
      Comparisons of individual sponges based on the UniFrac P-test also revealed
      significant differences in community composition between individual sponges. The
      sponges harbored a variety of phylum level operational taxonomic units (OTUs)
      common to many sponges, including Cyanobacteria, Poribacteria, Acidobacteria,
      Chloroflexi, and Gemmatimonadetes, but four additional symbiotic phyla,
      previously not reported for this sponge, were observed. Additionally, a diverse
      archaeal community was also recovered from X. muta including sequences
      representing the phyla Euryarchaeota and Thaumarchaeota. These results have
      important ecological implications for the understanding of host-microbe
      associations, and provide a foundation for future studies addressing the
      functional roles these symbiotic prokaryotes have in the biology of the host
      sponge and the nutrient biogeochemistry of coral reefs. 

PMID- 24124114
TI  - Protein misfolding and aggregation research: some thoughts on improving quality
      and utility.
AB  - Once misfolded and aggregated proteins were as interesting as yesterday's trash,
      just a bothersome byproduct of productive activities. Today, they attract
      sustained interest from both basic researchers and practicing engineers. In the
      burgeoning biopharmaceutical industry, protein misfolding and aggregation pose
      significant challenges to the economic manufacture of safe and effective protein
      products. In the clinic, protein aggregates are believed to be pathological
      agents in a number of serious neurodegenerative disorders, such as Alzheimer's
      and Parkinson's. Over the past few years, the quantity of research into
      biotechnological aspects of protein misfolding and aggregation has skyrocketed.
      However, the quality of the published work is quite variable. In this brief
      opinion piece, we describe what we believe are some key features of high-quality
      publications in protein aggregation. We focus on experimental studies that may
      also have a kinetic modeling component.

PMID- 24124113
TI  - Insulin sensitivity and insulin clearance are heritable and have strong genetic
      correlation in Mexican Americans.
AB  - OBJECTIVE: The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is
      described, along with heritability estimates and genetic and environmental
      correlations of insulin sensitivity and metabolic clearance rate of insulin
      (MCRI). METHODS: GUARDIAN is comprised of seven cohorts, consisting of 4,336
      Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI,
      and acute insulin response (AIRg) were measured by frequently sampled intravenous
      glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI
      were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability
      and genetic and environmental correlations were estimated within the family
      cohorts (totaling 3,925 individuals) using variance components. RESULTS: Across
      studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M,
      M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the
      genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59
      for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations
      were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg
      and MCRI (P < 0.0001-0.06). CONCLUSIONS: These data support a strong familial
      basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic
      correlations between MCRI and SI suggest common genetic determinants.

PMID- 24124116
TI  - Cholecystectomy by using a surgical robotic system.
AB  - Because of their frequency, hepato-biliary procedures have been the gateway for
      innovation to permeate into the realm of general surgery. Robotics and single
      incision techniques are the latest manifestation in the evolution of minimally
      invasive surgery. Enthusiasm for the latter has increased due to its inarguably
      superior cosmetic result. Nevertheless, there are several technical disadvantages
      associated with this approach that have raised several concerns. The robotic
      platform may provide a solution to these issues. We analyze the strengths and
      weaknesses of the robotic system for cholecystectomy and its relation to single
      site technology. We review all available literature addressing robotic single
      site cholecystectomy. Due to the advent of specific robotic single site
      technology, many of the challenges commonly associated with single site
      cholecystectomy have been alleviated. Although this novel approach has not yet
      been extensively tested, the available evidence suggests that it is at least
      equivalent to LC in selected patients. Robotic single site cholecystectomy is
      safe and feasible and adequately compensates for many of the challenges commonly
      associated with conventional single site cholecystectomy. Large, high-quality
      studies are needed to further clarify the role of this procedure and its value as
      part of the surgeon's armamentarium. 

PMID- 24124115
TI  - Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin
      syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.
AB  - Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal
      dominant condition mainly characterized by the development of mandibular
      keratocysts which often have their onset during the second decade of life and/or
      multiple basal cell carcinoma (BCC) normally arising during the third decade.
      Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the
      childhood brain malignancy medulloblastoma (now often called primitive neuro
      ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is
      not clearly increased, although lymphoma and meningioma can occur in this
      condition. Wilms tumor has been mentioned in the literature four times. We
      describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1
      that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor,
      multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung
      typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical
      presentation. We propose including leiomyomas among minor criteria of the NBCCS.

PMID- 24124117
TI  - Effect of (D)-fagomine on excreted Enterobacteria and weight gain in rats fed a
      high-fat high-sucrose diet.
AB  - OBJECTIVE: Becoming overweight has been related to elevated levels of
      Enterobacteriales in the gut. d-Fagomine is an iminosugar that has been shown to
      selectively agglutinate Enterobacteriales in vitro. The goal of this work is to
      establish whether d-fagomine exerts a similar effect in vivo and whether this has
      any downstream consequences on weight gain. METHODS: The rats were fed a high-fat
      high-sucrose diet (HFHS) supplemented with d-fagomine (or not; for comparison) or
      a standard diet for 5 weeks. The levels of total bacteria, Enterobacteriales and
      Escherichia coli were determined in fecal samples by performing quantitative real
      time polymerase chain reactions on DNA. RESULTS: Whereas the total levels of
      bacteria were independent of the diet, rats fed HFHS (without d-fagomine)
      excreted significantly higher proportions of Enterobacteriales and E. coli than
      those fed a standard diet. The levels of Enterobacteriales and E. coli of the
      rats given HFHS with d-fagomine were similar to those of the rats fed a standard
      diet. Compared to the standard group, rats fed HFHS with d-fagomine gained
      significantly less weight (15.3%) than those fed HFHS (20.9%). CONCLUSION: d
      Fagomine reduces the amount of Enterobacteriales excreted by rats fed HFHS and
      this may help to avert becoming obese.

PMID- 24124118
TI  - Nanofibers implant functionalized by neural growth factor as a strategy to
      innervate a bioengineered tooth.
AB  - Current strategies for jaw reconstruction require multiple procedures, to repair
      the bone defect, to offer sufficient support, and to place the tooth implant. The
      entire procedure can be painful and time-consuming, and the desired functional
      repair can be achieved only when both steps are successful. The ability to
      engineer combined tooth and bone constructs, which would grow in a coordinated
      fashion with the surrounding tissues, could potentially improve the clinical
      outcomes and also reduce patient suffering. A unique nanofibrous and active
      implant for bone-tooth unit regeneration and also the innervation of this
      bioengineered tooth are demonstrated. A nanofibrous polycaprolactone membrane is
      functionalized with neural growth factor, along with dental germ, and tooth
      innervation follows. Such innervation allows complete functionality and tissue
      homeostasis of the tooth, such as dentinal sensitivity, odontoblast function,
      masticatory forces, and blood flow. 

PMID- 24124119
TI  - Vitamin D supplementation to prevent osteoporosis is not warranted, study
      concludes.

PMID- 24124120
TI  - Editor's forward to special articles: elements of morphology.

PMID- 24124121
TI  - A brief self-affirmation study to improve the experience of minority patients.
AB  - BACKGROUND: There is evidence that Black patients may experience stereotype
      threat--apprehension about being negatively stereotyped--in healthcare settings,
      which might adversely affect their behavior in clinical encounters. Recent
      studies conducted outside of healthcare have shown that a brief self-affirmation
      intervention, in which individuals are asked to focus on and affirm their valued
      characteristics and sources of personal pride, can reduce the negative effects of
      stereotype threat on academic performance and on interpersonal communication.
      METHODS: This randomised controlled trial examined whether a self-affirmation
      (SA) intervention would decrease the negative effects of stereotype threat
      (negative mood, lower state self-esteem, greater perceptions of racial
      discrimination) and increase communication self-efficacy among Black primary care
      patients. Self-affirmation was induced by having patients complete a 32-item
      values affirmation questionnaire. RESULTS: Patients in the SA condition had lower
      levels of performance self-esteem and social self-esteem than patients in the
      control. There were no differences between the SA and the control groups on
      negative mood, communication self-efficacy, and perceptions of discrimination.
      CONCLUSIONS: Our SA intervention lowered state self-esteem among Black patients.
      Future research is needed to determine the type of SA task that is most effective
      for this population.

PMID- 24124122
TI  - Altered peripheral and central inflammatory responses in a mouse model of autism.
AB  - Increasing clinical and experimental evidence links immune and inflammatory
      alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic
      individuals show signs of neuroinflammation, altered inflammatory responses, and
      immune abnormalities throughout life. Mice injected subcutaneously with 600 mg/kg
      valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in
      adulthood (at 8 weeks of age), and they have been proposed as a mouse model of
      autism. Here, we show that these adult animals present signs of chronic glial
      activation in the hippocampus and the cerebellum. Moreover, when they are
      challenged with a peripheral inflammatory stimulus (intraperitoneal
      lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory
      response. Two hours after LPS injection, VPA600 animals secrete more
      corticosterone to the blood than control mice, and show an increase in the levels
      of expression of proinflammatory cytokines in the spleen. After LPS challenge,
      VPA600 mice also show signs of increased neuroinflammation compared with control
      mice: they have more microglial cells in the hippocampus, and they show higher
      levels of proinflammatory cytokines in the cerebellum. Our results provide
      evidence of basal neuroinflammation and an altered inflammatory response in the
      VPA model of autism. We propose that this model can be used to evaluate the
      contribution of inflammatory reactivity to autism-related behaviors. These
      studies will contribute to elucidate the role of the inflammatory alterations
      observed in ASD individuals.

PMID- 24124123
TI  - Polymer blend particles with defined compositions for targeting antigen to both
      class I and II antigen presentation pathways.
AB  - Defense against many persistent and difficult-to-treat diseases requires a
      combination of humoral, CD4(+) , and CD8(+) T-cell responses, which necessitates
      targeting antigens to both class I and II antigen presentation pathways. In this
      study, polymer blend particles are developed by mixing two functionally unique
      polymers, poly(lactide-co-glycolide) (PLGA) and a pH-responsive polymer,
      poly(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate)
      (DMAEMA-co-PAA-co-BMA). Polymer blend particles are shown to enable the delivery
      of antigens into both class I and II antigen presentation pathways in vitro.
      Increasing the ratio of the pH-responsive polymer in blend particles increases
      the degree of class I antigen presentation, while maintaining high levels of
      class II antigen presentation. In a mouse model, it is demonstrated that a
      significantly higher and sustained level of CD4(+) and CD8(+) T-cell responses,
      and comparable antibody responses, are elicited with polymer blend particles than
      PLGA particles and a conventional vaccine, Alum. The polymer blend particles
      offer a potential vaccine delivery platform to generate a combination of humoral
      and cell-mediated immune responses that insure robust and long-lasting immunity
      against many infectious diseases and cancers.

PMID- 24124125
TI  - Effects of ovalbumin glycoconjugates on alleviation of orally induced egg allergy
      in mice via dendritic-cell maturation and T-cell activation.
AB  - SCOPE: Glycation of allergens via Maillard reaction or chemical conjugation has
      been shown to influence susceptibility to food-induced allergies. It is
      hypothesized that mucosal immune response bias can be favorably altered by orally
      administering various forms of glycated ovalbumin (OVA). METHODS AND RESULTS:
      Groups of Balb/c mice (n = 10) were orally sensitized to OVA and administered
      various forms of glycated OVA (glucose, mannose, glucomannan, galactomannan, and
      a mixture containing OVA and glucomannan). Outcomes post oral challenge were
      measured as clinical allergic signs, serum histamine, mouse mast cell protease 1
      (MMCP-1), antibody activity, type-1/2 cytokines, percentage of T-regulatory cells
      (T-regs) and in vitro dendritic cell, and T-cell-related mechanisms. Clinical
      signs and specific IgE were decreased (p <= 0.05), and T-reg cell percentage was
      increased in the mannose and glucomannan treated groups. The OVA-mannose group
      also had less histamine, MMCP-1, specific IgG, IL-4 and IL-17, and more IL-12p70
      (p <= 0.05). Other parameters measured did not differ significantly among groups.
      Also, OVA-glycated mannose reduced maturation and uptake by dendritic cells. Less
      activation of T cells and type-2 cytokine response in DC-T-cell cocultures were
      observed with OVA-glycated mannose stimulation. CONCLUSION: This study validates,
      for the first time, the use of OVA-glycated mannose and glucomannan for potential
      beneficial dietary interventions for allergy.

PMID- 24124124
TI  - Hormone suppression with GnRH antagonist promotes spermatogenic recovery from
      transplanted spermatogonial stem cells in irradiated cynomolgus monkeys.
AB  - Hormone suppression given before or after cytotoxic treatment stimulates the
      recovery of spermatogenesis from endogenous and transplanted spermatogonial stem
      cells (SSC) and restores fertility in rodents. To test whether the combination of
      hormone suppression and transplantation could enhance the recovery of
      spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult
      cynomolgus monkeys and treated six of them with gonadotropin-releasing hormone
      antagonist (GnRH-ant) for 8 weeks. At the end of this treatment, we transfected
      cryopreserved testicular cells with green fluorescent protein-lentivirus and
      autologously transplanted them back into one of the testes. The only significant
      effect of GnRH-ant treatment on endogenous spermatogenesis was an increase in the
      percentage of tubules containing differentiated germ cells (tubule
      differentiation index; TDI) in the sham-transplanted testes of GnRH-ant-treated
      monkeys compared with radiation-only monkeys at 24 weeks after irradiation.
      Although transplantation alone after irradiation did not significantly increase
      the TDI, detection of lentiviral DNA in the spermatozoa of one radiation-only
      monkey indicated that some transplanted cells colonized the testis. However, the
      combination of transplantation and GnRH-ant clearly stimulated spermatogenic
      recovery as evidenced by several observations in the GnRH-ant-treated monkeys
      receiving transplantation: (i) significant increases (~20%) in the volume and
      weight of the testes compared with the contralateral sham-transplanted testes
      and/or to the transplanted testes of the radiation-only monkeys; (ii) increases
      in TDI compared to the transplanted testes of radiation-only monkeys at 24 weeks
      (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii)
      detection of lentiviral sequences in the spermatozoa or testes of five of the
      GnRH-ant-treated monkeys and (iv) significantly higher sperm counts than in the
      radiation-only monkeys. Thus hormone suppression enhances spermatogenic recovery
      from transplanted SSC in primates and may be a useful tool in conjunction with
      spermatogonial transplantation to restore fertility in men after cancer
      treatment. 

PMID- 24124126
TI  - Light emission in water-containing cocrystals: the influence of water molecules
      on the fluorescence properties of a Schiff-base molecule.
AB  - In the presence or absence of water, a Schiff-base compound, 4-amino-3-(2-(2
      hydroxybenzylidene)hydrazinyl)-1H-1,2,4-triazole-5(4H)-thione (HATT), forms
      different crystalline states (HATT, HATT.2H2O, and a lamellar structure, m
      HATT.nH2O), which show different luminescence emission properties. Herein, we
      investigate the emission of HATT and the role of water molecules. A water
      molecule, which acts as both a hydrogen-bond acceptor and -donor, enlarges the
      distance between adjacent HATT molecules and hinders non-radiative decay
      pathways.

PMID- 24124127
TI  - Global combined precursor isotopic labeling and isobaric tagging (cPILOT)
      approach with selective MS(3) acquisition.
AB  - Recently, we reported a novel proteomics quantitation scheme termed "combined
      precursor isotopic labeling and isobaric tagging (cPILOT)" that allows for the
      identification and quantitation of nitrated peptides in as many as 12-16 samples
      in a single experiment. cPILOT offers enhanced multiplexing and posttranslational
      modification specificity, however excludes global quantitation for all peptides
      present in a mixture and underestimates reporter ion ratios similar to other
      isobaric tagging methods due to precursor co-isolation. Here, we present a novel
      chemical workflow for cPILOT that can be used for global tagging of all peptides
      in a mixture. Specifically, through low pH precursor dimethylation of tryptic or
      LysC peptides followed by high pH tandem mass tags, the same reporter ion can be
      used twice in a single experiment. Also, to improve triple-stage mass
      spectrometry (MS(3) ) data acquisition, a selective MS(3) method that focuses on
      product selection of the y1 fragment of lysine-terminated peptides is
      incorporated into the workflow. This novel cPILOT workflow has potential for
      global peptide quantitation that could lead to enhanced sample multiplexing and
      increase the number of quantifiable spectra obtained from MS(3) acquisition
      methods. 

PMID- 24124128
TI  - Customization of copolymers to optimize selectivity and yield in polymer-driven
      antibody purification processes.
AB  - This manuscript describes customization of copolymers to be used for polymer
      driven protein purification in bioprocessing. To understand how copolymer
      customization can be used for fine-tuning, precipitation behavior was analyzed
      for five target antibodies (mAbs) and BSA as model impurity protein, at ionic
      strength similar to undiluted cell culture fluid. In contrast to the use of
      standardized homopolymers, customized copolymers, composed of 2-acrylamido-2
      methylpropane sulfonic acid (AMPS) and 4-(acryloylamino)benzoic acid (ABZ),
      exhibited antibody precipitation yields exceeding 90%. Additionally, copolymer
      average molecular weight (Mw ) was varied and its influence on precipitation
      yield and contaminant coprecipitation was investigated. Results revealed
      copolymer composition as the major driving force for precipitation selectivity,
      which was also dependent on protein hydrophobicity. By adjusting ABZ content and
      Mw of the precipitant for each of the mAbs, conditions were found that allowed
      for high precipitation yield and selectivity. These findings may open up new
      avenues for using polymers in antibody purification processes.

PMID- 24124130
TI  - The evolving application of single-port robotic surgery in general surgery.
AB  - Advances in the field of minimally invasive surgery have grown since the original
      advent of conventional multiport laparoscopic surgery. The recent development of
      single incision laparoscopic surgery remains a relatively novel technique, and
      has had mixed reviews as to whether it has been associated with lower pain
      scores, shorter hospital stays, and higher satisfaction levels among patients
      undergoing procedures through cosmetically-appeasing single incisions. However,
      due to technical difficulties that arise from the clustering of laparoscopic
      instruments through a confined working space, such as loss of instrument
      triangulation, poor surgical exposure, and instrument clashing, uptake by
      surgeons without a specific interest and expertise in cutting-edge minimally
      invasive approaches has been limited. The parallel use of robotic surgery with
      single-port platforms, however, appears to counteract technical issues associated
      with single incision laparoscopic surgery through significant ergonomic
      improvements, including enhanced instrument triangulation, organ retraction, and
      camera localization within the surgical field. By combining the use of the robot
      with the single incision platform, the recognized challenges of single incision
      laparoscopic surgery are simplified, while maintaining potential advantages of
      the single-incision minimally invasive approach. This review provides a
      comprehensive report of the evolving application single-port robotic surgery in
      the field of general surgery today. 

PMID- 24124129
TI  - CXCR3 modulates obesity-induced visceral adipose inflammation and systemic
      insulin resistance.
AB  - OBJECTIVE: Chemokine (C-X-C motif) receptor 3 (CXCR3) is a chemokine receptor
      involved in the regulation of immune cell trafficking and activation. Increased
      CXCR3 expression in the visceral adipose of obese humans and mice was observed. A
      pathophysiologic role for CXCR3 in diet-induced obesity (DIO) was hypothesized.
      METHODS: Wild-type (WT) C57B/L6J and chemokine receptor 3 knockout (CXCR3(-/-) )
      mice were fed a high-fat diet (HFD) for 20 weeks followed by assessment of
      glucose metabolism and visceral adipose tissue (VAT) inflammation. RESULTS:
      CXCR3(-/-) mice exhibited lower fasting glucose and improved glucose tolerance
      compared with WT-HFD mice, despite similar body mass. HFD-induced VAT innate and
      adaptive immune cell infiltration, including immature myeloid cells (CD11b(+)
      F4/80(lo) Ly6C(+) ), were markedly ameliorated in CXCR3(-/-) mice. In vitro IBIDI
      and in vivo migration assays demonstrated no CXCR3-mediated effect on macrophage
      or monocyte migration, respectively. CXCR3(-/-) macrophages, however, had a
      blunted response to interferon-gamma, a TH 1 cytokine that induces macrophage
      activation. CONCLUSIONS: A previously unreported role for CXCR3 in the
      development of HFD-induced insulin resistance (IR) and VAT macrophage
      infiltration in mice was demonstrated. Our results support pharmaceutical
      targeting of the CXCR3 receptor as a potential treatment for obesity/IR.

PMID- 24124131
TI  - The emerging role of SHANK genes in neuropsychiatric disorders.
AB  - The genetic heterogeneity of neuropsychiatric disorders is high, but some
      pathways emerged, notably synaptic functioning. A large number of mutations have
      been described in genes such as neuroligins, neurexins, and SHANK that play a
      role in the formation and the maintenance of synapses. This review focuses on the
      disorders associated with mutations in SHANK3 and the other members of its
      family, SHANK1 and SHANK2. SHANKs are scaffolding proteins of the postsynaptic
      density of glutamatergic synapses. SHANK3 has been described in the Phelan
      McDermid syndrome (PMS), but also in autism spectrum disorders (ASD) and
      schizophrenia associated to moderate to severe intellectual disability (ID) and
      poor language. The evolution of patients with PMS includes symptoms of bipolar
      disorder and regression. SHANK2 has been identified in patients with ASD with
      mild to severe ID. SHANK1 has been associated with high-functioning autism in
      male patients, while carrier females only display anxiety and shyness. Finally,
      based on neuropathological findings in animal models and patients, a possible
      role of SHANK in Alzheimer's disease is discussed. Altogether, this review
      describes the clinical trajectories associated with different mutations of the
      SHANK genes and provides information to further investigate the role of the SHANK
      genes in neuropsychiatric disorders.

PMID- 24124132
TI  - Osteotropic therapy via targeted layer-by-layer nanoparticles.
AB  - Current treatment options for debilitating bone diseases such as osteosarcoma,
      osteoporosis, and bone metastatic cancer are suboptimal and have low efficacy.
      New treatment options for these pathologies require targeted therapy that
      maximizes exposure to the diseased tissue and minimizes off-target side effects.
      This work investigates an approach for generating functional and targeted drug
      carriers specifically for treating primary osteosarcoma, a disease in which
      recurrence is common and the cure rate has remained around 20%. This approach
      utilizes the modularity of Layer-by-Layer (LbL) assembly to generate tissue
      specific drug carriers for systemic administration. This is accomplished via
      surface modification of drug-loaded nanoparticles with an aqueous
      polyelectrolyte, poly(acrylic acid) (PAA), side-chain functionalized with
      alendronate, a potent clinically used bisphosphonate. Nanoparticles coated with
      PAA-alendronate are observed to bind and internalize rapidly in human
      osteosarcoma 143B cells. Encapsulation of doxorubicin, a front-line
      chemotherapeutic, in an LbL-targeted liposome demonstrates potent toxicity in
      vitro. Active targeting of 143B xenografts in NCR nude mice with the LbL-targeted
      doxorubicin liposomes promotes enhanced, prolonged tumor accumulation and
      significantly improved efficacy. This report represents a tunable approach
      towards the synthesis of drug carriers, in which LbL enables surface modification
      of nanoparticles for tissue-specific targeting and treatment. 

PMID- 24124133
TI  - Do individuals with and without autism spectrum disorder scan faces differently?
      A new multi-method look at an existing controversy.
AB  - Individuals with autism spectrum disorder (ASD) are known to process faces
      atypically. However, there has been considerable controversy regarding whether
      ASD individuals also scan faces differently from typical adults. Here we compared
      ASD individuals' face-scanning patterns with those of typically developing (TD)
      controls and intellectually disabled (ID) but non-ASD individuals with the use of
      an eye tracker and multiple approaches to analyze eye-tracking data. First, we
      analyzed the eye movement data with a traditional approach, measuring fixation
      duration on each area of interest within the face. We found that compared with TD
      and ID individuals, ASD individuals looked significantly shorter at the right
      eye. Second, we used a data-driven method that analyzes fixations on each pixel
      of the face stimulus and found that individuals with ASD looked more at the
      central nasal area than TD and ID individuals. Third, we used a novel saccade
      path analysis that measures frequencies of saccades between major face areas. We
      found that ASD individuals scanned less often between core facial features than
      TD individuals but did not differ from ID individuals. Findings from the multi
      method approaches show that individuals with ASD appear not to have a pervasive
      ASD-specific atypicality in visual attention toward the face. The ASD-specific
      atypical face-scanning patterns were shown to be limited to fixations on the eyes
      and nose.

PMID- 24124134
TI  - Proteome of brain glia: the molecular basis of diverse glial phenotypes.
AB  - Several different types of nonneuronal glial cells with diverse phenotypes are
      present in the CNS, and all have distinct indispensible functions. Although glial
      cells primarily provide neurons with metabolic and structural support in the
      healthy brain, they may switch phenotype from a "resting" to a "reactive" state
      in response to pathological insults. Furthermore, this reactive gliosis is an
      invariant feature of the pathogeneses of CNS maladies. The glial proteome serves
      as a signature of glial phenotype, and not only executes physiological functions,
      but also acts as a molecular mediator of the reactive glial phenotype. The glial
      proteome is also involved in intra- and intercellular communications as
      exemplified by glia-glia and neuron-glia interactions. The utilization of
      authoritative proteomic tools and the bioinformatic analyses have helped to
      profile the brain glial proteome and explore the molecular mechanisms of diverse
      glial phenotypes. Furthermore, technologic innovations have equipped the field of
      "glioproteomics" with refined tools for studies of the expression, interaction,
      and function of glial proteins in the healthy and in the diseased CNS.
      Glioproteomics is expected to contribute to the elucidation of the molecular
      mechanisms of CNS pathophysiology and to the discovery of biomarkers and
      theragnostic targets in CNS disorders. 

PMID- 24124135
TI  - Synthesis of highly stable, water-dispersible copper nanoparticles as catalysts
      for nitrobenzene reduction.
AB  - We report an aqueous-phase synthetic route to copper nanoparticles (CuNPs) using
      a copper-surfactant complex and tests of their catalytic efficiency for a simple
      nitrophenol reduction reaction under atmospheric conditions. Highly stable, water
      dispersed CuNPs were obtained with the aid of polyacrylic acid (PAA), but not
      with other dispersants like surfactants or polymethacrylic acid (PMAA). The
      diameter of the CuNPs could be controlled in the range of approximately 30-85 nm
      by modifying the ratio of the metal precursor to PAA. The catalytic reduction of
      p-nitrophenol to p-aminophenol takes place at the surface of CuNPs at room
      temperature and was accurately monitored by UV/Vis spectroscopy. The catalytic
      efficiency was found to be remarkably high for these PAA-capped CuNPs, given the
      fact that at the same time PAA is efficiently preventing their oxidation as well.
      The activity was found to increase as the size of the CuNPs decreased. It can
      therefore be concluded that the synthesized CuNPs are catalytically highly
      efficient in spite of the presence of a protective PAA coating, which provides
      them with a long shelf life and thereby enhances the application potential of
      these CuNPs.

PMID- 24124136
TI  - Evaluation of human sperm chromatin status after selection using a modified Diff
      Quik stain indicates embryo quality and pregnancy outcomes following in vitro
      fertilization.
AB  - Sperm chromatin/DNA damage can be measured by a variety of assays. However, it
      has been reported that these tests may lose prognostic value in Assisted
      Reproductive Technology (ART) cycles when assessed in post-prepared samples,
      possibly due to the normalizing effect promoted by sperm preparation procedures.
      We have recently implemented a modified version of the Diff-Quik staining assay
      that allows for the evaluation of human sperm chromatin status in native samples,
      together with standard sperm morphology assessment. However, the value of this
      parameter in terms of predicting in vitro fertilization (IVF) and
      Intracytoplasmic sperm injection (ICSI) outcomes after sperm selection is
      unknown. In this study, data from 138 couples undergoing in vitro fertilization
      (IVF) or Intracytoplasmic sperm injection (ICSI) treatments showed that sperm
      chromatin integrity was significantly improved after density gradient
      centrifugation and swim up (p < 0.001), but no correlations were found with
      fertilization or embryo development rates (p > 0.05). However, sperm samples
      presenting lower percentages of damaged chromatin were associated with better
      quality (Grade I) embryos in both ART procedures (p < 0.05) and clinical
      pregnancy among IVF couples (p < 0.05). Furthermore, regression analysis
      confirmed the clinical value of Diff-Quik staining in predicting IVF (but not
      ICSI) clinical pregnancy (OR: 0.927, 95% CI: 0.871-0.985, p = 0.015), and a
      threshold value of 34.25% for this parameter was established. The proportion of
      IVF couples achieving a clinical pregnancy was reduced 1.9-fold when the
      percentage of abnormal dark staining was >=34.25% (p = 0.05). In conclusion, the
      Diff-Quik staining assay provides useful information regarding ART success,
      particularly in IVF cycles, where some degree of 'natural' sperm selection may
      occur; but not in ICSI, where sperm selection is operator dependent. This quick
      and low-cost assay is suggested as an alternative method to detect sperm
      chromatin status in minimal clinical settings, when no other well-established and
      robust assays (e.g. Sperm chromatin structure assay, terminal deoxynucleotidyl
      transferase-mediated dUDP nick-end labelling) are available. 

PMID- 24124137
TI  - Anticoagulation without monitoring.

PMID- 24124138
TI  - Intraoperative diagnosis miscommunication: an opportunity for improvement.

PMID- 24124139
TI  - Pathology consultation on monitoring direct thrombin inhibitors and overcoming
      their effects in bleeding patients.
AB  - OBJECTIVES: Direct thrombin inhibitors (DTIs), a relatively new class of
      anticoagulants, present several challenges regarding monitoring of their
      anticoagulant effects and overcoming bleeding associated with their use. The aim
      of this article is to (1) briefly present the pharmacologic properties of
      currently available DTIs, (2) discuss approaches to laboratory assessment of
      these drugs, and (3) review management of bleeding associated with their use.
      METHODS: Published literature on DTIs, including clinical trials, case reports,
      and experimental animal models, was reviewed. The primary authors also reviewed
      their first-hand experiences with DTI anticoagulation. RESULTS: Based on the
      literature review and the practical experiences of the authors, suggestions for
      the monitoring of DTIs and algorithmic approaches for the management of DTI
      associated bleeding were developed. CONCLUSIONS: Routine coagulation assays (eg,
      the prothrombin time) show a relatively poor correlation with the degree of
      anticoagulation and DTI drug concentrations. Newer assays, such as the ecarin
      clotting time and dilute thrombin time, may be more useful in assessing DTI
      anticoagulation, but these assays are not yet widely available. Low-grade DTI
      associated bleeds are best managed with cessation of the drug and supportive
      care, while higher-grade and/or life-threatening bleeds may best be reversed by
      active drug removal (eg, via the administration of activated charcoal or
      hemodialysis). At present there is little evidence to suggest that transfusion
      products such as factor concentrates or thawed plasma are of any particular
      benefit in DTI reversal; however, these products may play a supportive role in
      the management of bleeding.

PMID- 24124140
TI  - Pathology consultation on anticoagulation monitoring: factor X-related assays.
AB  - OBJECTIVES: To review various anticoagulation therapies and related laboratory
      monitoring issues, with a focus on factor X-related chromogenic assays. METHODS:
      A case-based approach is used to review pertinent published literatures and
      product inserts of anticoagulation drugs and to look back on clinical use of
      factor X-related chromogenic assays. RESULTS: The number of anticoagulants
      available to clinicians has increased greatly in the past decade. Whether and how
      these anticoagulants should be monitored are areas of uncertainty for clinicians,
      which can lead to misuse of laboratory assays and suboptimal patient management.
      Factor X-related assays are of particular concern because of the similar and
      often confusing test names. Based on a common clinical case scenario and
      literature review regarding anticoagulant monitoring, an up-to-date discussion
      and review of the various factor X-related assays are provided, focusing on the
      differences in test designs and clinical utilities between the chromogenic anti
      Xa and chromogenic factor X activity assays. CONCLUSIONS: Anticoagulation therapy
      and related laboratory monitoring are rapidly evolving areas of clinical
      practices. A good knowledge of relevant laboratory assays and their clinical
      applications is necessary to help optimize patient care.

PMID- 24124141
TI  - Fine-needle aspiration cytology for the diagnosis of metastatic melanoma:
      systematic review and meta-analysis.
AB  - OBJECTIVES: To perform a thorough review and meta-analysis of studies that have
      shown non-image-guided fine-needle aspiration cytology (FNAC) to be highly
      sensitive and specific for assessing questionable metastatic melanoma to lymph
      nodes. METHODS: MEDLINE and Scopus were searched for potentially relevant
      articles with a search string including the words "melanoma" and "fine needle."
      All relevant articles were screened by two authors (B.J.H. and R.L.S.). Full
      articles were screened for extractable data, and the data was pooled for
      analysis. RESULTS: Of 978 unique studies found, 10 (5,518 cases) met our
      inclusion criteria. In a pooled analysis of palpation and ultrasound-guided fine
      needle aspirations, the area under the receiver operating characteristic curve
      was 0.99 (95% confidence interval [CI], 0.99-1.00). The summary estimates for the
      sensitivity and specificity were 0.97 (95% CI, 0.95-0.98) and 0.98 (95% CI, 0.98
      1.00), respectively. CONCLUSIONS: With a sensitivity and specificity of 0.97 and
      0.99, the overall diagnostic accuracy of FNAC for metastatic melanoma is quite
      high, and with a positive and negative likelihood ratio of 58 and 0.03, FNAC for
      metastatic melanoma should be the first-line option in a patient with a
      clinically suspected mass and a history of melanoma.

PMID- 24124142
TI  - Optimizing personalized bone marrow testing using an evidence-based,
      interdisciplinary team approach.
AB  - OBJECTIVES: To address the overuse of testing that complicates patient care,
      diminishes quality, and increases costs by implementing the diagnostic management
      team, a multidisciplinary system for the development and deployment of diagnostic
      testing guidelines for hematologic malignancies. METHODS: The team created
      evidence-based standard ordering protocols (SOPs) for cytogenetic and molecular
      testing that were applied by pathologists to bone marrow biopsy specimens on
      adult patients. Testing on 780 biopsy specimens performed during the six months
      before SOP implementation was compared with 1,806 biopsy specimens performed
      during the subsequent 12 months. RESULTS: After implementation, there were
      significant decreases in tests discordant with SOPs, omitted tests, and the
      estimated cost of testing to payers. The fraction of positive tests increased.
      Clinicians reported acceptance of the new procedures and perceived time savings.
      CONCLUSIONS: This process is a model for optimizing complex and personalized
      diagnostic testing.

PMID- 24124143
TI  - How well do we communicate?: a comparison of intraoperative diagnoses listed in
      pathology reports and operative notes.
AB  - OBJECTIVES: To compare surgeons' interpretations of intraoperative diagnoses with
      those rendered by the pathologist. METHODS: Consecutive intraoperative diagnoses
      over a nine-month period were retrospectively reviewed. For each case, operative
      notes were obtained from the hospital information system. The intraoperative
      diagnoses listed in the final pathology reports were compared with those dictated
      by the surgeon. Discrepancies were stratified by potential clinical impact:
      category A, overall correct diagnosis with minor unimportant differences;
      category B, discrepant diagnosis with both either benign or malignant; and
      category C, intraoperative diagnoses differing between benign and malignant. The
      method of communication of each discrepant intraoperative diagnoses (in person vs
      telephone) was also examined. RESULTS: There was no record of the intraoperative
      diagnoses in 20% of operative notes. Comparison of intraoperative diagnoses was
      possible in 1,131 cases. Category A errors were noted in 94 (8.3%) cases, B in 11
      (1%), and C in 4 (0.3%). The most frequent means of communication in A and B
      cases was the telephone, with more C cases being relayed in person. CONCLUSIONS:
      A subset of verbally reported intraoperative diagnoses is misinterpreted by
      surgeons. While rare events, miscommunication can lead to inappropriate
      intraoperative management. Communicating diagnoses by phone may increase the risk
      of perception errors.

PMID- 24124144
TI  - CD177 expression on neutrophils: in search of a clonal assay for myeloid
      neoplasia by flow cytometry.
AB  - OBJECTIVES: To determine whether the fraction of CD177+ neutrophils might be
      altered in clonal myeloid disorders, similar to the skewed kappa/lambda ratio for
      B-cell lymphomas, and could be used to identify myeloid neoplasms. METHODS: Blood
      and bone marrow samples were evaluated for the fraction of CD177+ neutrophils by
      flow cytometry. RESULTS: Skewed high neutrophil CD177(%) was not associated with
      neoplasia, but skewed low neutrophil CD177(%) was highly correlated with clonal
      myeloid disorders at values less than 40%. Specificity of low neutrophil CD177(%)
      for clonal myeloid disorders was 87% with a 40% cutoff and 95% with a 30% cutoff.
      Findings were most pronounced for myelodysplasia, with 52% (11/21) containing
      fewer than 40% CD177+ neutrophils. Specificity was also suggested by
      normalization of neutrophil CD177(%) in four patients who reached morphologic
      remission after therapy for myelodysplasia or acute leukemia. CONCLUSIONS: Skewed
      low neutrophil CD177(%) is highly associated with clonal myeloid disorders,
      particularly myelodysplasia, and may be useful for detecting clonal myeloid
      disorders.

PMID- 24124145
TI  - Are meningeal hemangiopericytoma and mesenchymal chondrosarcoma the same?: a
      study of HEY1-NCOA2 fusion.
AB  - OBJECTIVES: Meningeal hemangiopericytoma (HPC) and mesenchymal chondrosarcoma are
      aggressive neoplasms with a propensity to involve the meninges and dura. In
      addition to similar clinical presentations, both meningeal HPC and mesenchymal
      chondrosarcoma share overlapping morphologic features, including ovoid cells,
      variable collagen deposition, and a branching vascular pattern. Recently, a novel
      HEY1-NCOA2 fusion was reported as a recurrent event in mesenchymal
      chondrosarcomas. METHODS: Thirteen mesenchymal chondrosarcomas and 18 meningeal
      HPCs were identified from surgical pathology archives, and the tumors were
      evaluated for HEY1-NCOA2 fusion with reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULTS: HEY1-NCOA2 fusion transcript was detected in all six
      cases of mesenchymal chondrosarcoma but in none of the meningeal HPC cases (0/11)
      that were evaluable with RT-PCR. CONCLUSIONS: These results show that (1)
      meningeal HPC and mesenchymal chondrosarcoma are distinct at the molecular level,
      and (2) the identification of HEY1-NCOA2 can be used as an auxiliary diagnostic
      tool to differentiate these entities.

PMID- 24124146
TI  - The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin
      binding site antithrombin deficiency.
AB  - OBJECTIVES: Antithrombin is a progressive inhibitor of active factor X (FXa) and
      thrombin (FIIa). Its effect is 500- to 1,000-fold accelerated by heparin or
      heparan sulfate. Heterozygous type I (quantitative) and most type II
      (qualitative) antithrombin deficiencies highly increase the risk of venous
      thromboembolism (VTE), while homozygous mutations are lethal. The functional
      defect affecting the heparin-binding site confers moderate risk of VTE to
      heterozygous and high risk of VTE to homozygous individuals. METHODS:
      Antithrombin activity assays based on the inhibition of FIIa and FXa were
      compared for their efficiency in detecting heparin-binding site defects. RESULTS:
      With a single exception, in heterozygotes for heparin-binding site defects (n =
      20), anti-FIIa activities remained in the reference interval, while anti-FXa
      activities were uniformly decreased. In individuals who were homozygous for
      heparin-binding site mutations (n = 9), anti-FIIa activities were in the range of
      48% to 80%; the range of anti-FXa activities was 9% to 25%. Anti-FIIa and anti
      FXa activities in type I deficiencies and type II pleiotropic deficiency did not
      differ significantly. CONCLUSIONS: Anti-FXa antithrombin assay is recommended as
      a first-line test to detect type II heparin-binding site antithrombin deficiency.

PMID- 24124147
TI  - Elevated factor IX activity is associated with an increased odds ratio for both
      arterial and venous thrombotic events.
AB  - OBJECTIVES: Elevations of factor IX (FIX) are thought to contribute to thrombotic
      risk, but this has not been well characterized. We retrospectively sought to
      determine whether elevated FIX levels are a risk factor for thrombosis in 81
      adult subjects younger than 65 years (mean, 47 years) who were referred for
      evaluation of a hypercoagulable state. METHODS: Patients were classified by
      arterial transient ischemic attack/stroke (TIA/stroke, n = 62) or venous
      thromboembolism (VTE, n = 19) events. FIX activity testing was performed on all
      81 subjects and a reference group of 40 healthy individuals. RESULTS: Thirteen
      (21%) of 62 subjects with TIA/stroke and 5 (26%) of 19 subjects with VTE had
      elevated FIX activity. Odds ratios for TIA/stroke and VTE in subjects with
      elevated FIX activity were 3.7 (95% confidence interval [CI], 0.76-17.65) and 6.8
      (95% CI, 1.18-39.07), respectively. CONCLUSIONS: Our findings suggest an
      association between elevated FIX levels and both arterial and venous thrombotic
      events.

PMID- 24124148
TI  - Chronic myelomonocytic leukemia monocytes uniformly display a population of
      monocytes with CD11c underexpression.
AB  - OBJECTIVES: To examine the utility of CD11c expression on monocytes in normal
      controls and patients with chronic myelomonocytic leukemia (CMML) (n = 23) with
      flow cytometric immunophenotyping. METHODS: Twenty-three CMML samples and 10
      control bone marrows submitted for lymphoma staging without evidence of disease
      were examined. RESULTS: Monocytes in CMML samples ranged from 4% to 35%.
      Expression of at least one aberrant monocytic marker was found on the monocytes
      in 18 (82%) of 22 evaluable cases. The most common aberrancy was underexpression
      of CD11c (n = 15), while none of the bone marrow controls showed underexpression
      of CD11c. CONCLUSIONS: A distinct heterogeneous population of monocytic cells
      with underexpression of CD11c was identified in all these cases. CD11c
      underexpression was independent of other aberrancies, including HLA-DR
      underexpression (n = 14), aberrant CD56 expression (n = 11), and underexpression
      of CD33, CD38, and CD14 (n = 6, 5, and 5, respectively), supporting the utility
      of CD11c expression status on monocytes in establishing a CMML diagnosis.

PMID- 24124149
TI  - Clinicopathologic features of CD5-positive nodal marginal zone lymphoma.
AB  - OBJECTIVES: To describe the clinicopathologic findings of seven patients with CD5
      positive nodal marginal zone lymphoma (NMZL). METHODS: We searched cases of NMZL
      over a 10-year interval and identified seven cases of CD5-positive NMZL. The
      clinical, histologic, and immunophenotypic findings of this group were reviewed,
      and the frequency of dissemination in this group was compared with that of 66
      patients with CD5-negative NMZL. RESULTS: Other than CD5 expression, the
      histologic and immunophenotypic findings were typical of NMZL. Six (86%) of seven
      patients had lymphadenopathy above and below the diaphragm, and all six patients
      assessed had bone marrow involvement. In the CD5-negative group, 28 (42%)
      patients had lymphadenopathy above and below the diaphragm, and 36 (55%) had bone
      marrow involvement (P = .045 and P = .037, respectively). Six of seven patients
      were alive at last follow-up, with a median follow-up of 32 months (3-154
      months). CONCLUSIONS: CD5 expression in NMZL correlates with a higher frequency
      of dissemination, but patients have an indolent clinical course and excellent
      overall survival.

PMID- 24124150
TI  - MACC1 is related to colorectal cancer initiation and early-stage invasive growth.
AB  - OBJECTIVES: To investigate metastasis associated in colon cancer 1 (MACC1) and
      MET expression in colorectal adenoma, Tis, early-stage invasive (T1 and T2), and
      advanced adenocarcinoma with liver metastasis using immunohistochemistry.
      METHODS: Ninety-three paraffin-embedded colorectal tumor specimens were
      immunohistochemically analyzed for MACC1 and MET protein expression. RESULTS:
      MACC1 expression was upregulated in the transition from adenoma to Tis; its
      expression was further elevated during tumor progression from Tis to early
      invasive carcinoma. MET expression was constant from adenoma to Tis and to T1 but
      significantly increased as tumor progression to T2. Both MACC1 and MET expression
      were enhanced in advanced carcinoma with liver metastasis. CONCLUSIONS: Stepwise
      elevation of MACC1 expression in key points of colorectal cancer development
      suggests that MACC1 may contribute to cancer initiation and early invasive
      growth. High expression of both MACC1 and MET may relate to distant metastasis.

PMID- 24124151
TI  - Surveillance for recurrent cancers and vaginal epithelial lesions in patients
      with invasive cervical cancer after hysterectomy: are vaginal cytology and high
      risk human papillomavirus testing useful?
AB  - OBJECTIVES: To examine whether women who have had a hysterectomy for cervical
      cancer may be at an increased risk of vaginal epithelial lesions. METHODS: We
      studied 147 patients with invasive cervical carcinoma (76 squamous cell
      carcinomas [SCCs], 60 adenocarcinomas [ADCs], and 11 adenosquamous cell
      carcinomas) who were treated by hysterectomy and had vaginal pathologic follow-up
      for a mean period of 43.3 months. RESULTS: Of the patients, 15.0% (22/147)
      developed vaginal intraepithelial neoplasia (VAIN) or recurrence after
      hysterectomy, including two recurrent carcinomas and eight high-grade VAINs. More
      important, these high-grade VAINs or recurrent carcinomas were detected only in
      patients with cervical SCC within the first two years after hysterectomy but not
      in patients with cervical ADC. Eleven (23.4%) of 47 patients had at least one
      positive high-risk human papillomavirus (hrHPV) testing result during the follow
      up period, and VAIN was detected in 54.5% (6/11) of patients with an hrHPV
      positive result compared with 16.7% (6/36) with an hrHPV-negative result.
      CONCLUSIONS: Our results indicate that women with cervical cancer are at an
      increased risk of VAIN besides recurrence, and women with cervical SCC are more
      prone to high-grade VAIN/recurrence, especially within the first two years after
      hysterectomy. The significantly increased detection rate of VAINs/recurrence in
      the hrHPV-positive group suggests vaginal cytology and HPV cotesting might be the
      preferred method for surveillance in these women.

PMID- 24124152
TI  - Analytical and clinical performance of the epoc blood analysis system: experience
      at a large tertiary academic medical center.
AB  - OBJECTIVES: To describe validation and performance of epoc, a blood gas analysis
      point-of-care system, in a live clinical setting. METHODS: Data were collected
      for 156 epoc systems over 12 months. Preimplementation precision and correlation
      studies and postimplementation quality assurance data were collected, including
      test card, reader, and personal data assistant (PDA) failure rates. RESULTS: The
      coefficient of variation was clinically acceptable for all analytes. Correlation
      studies yielded an R(2) from 0.901 (for sodium) to 0.994 (for potassium) with the
      Nova analyzer and from 0.961 (sodium) to 0.991 (glucose) with the i-STAT. Average
      test card failure rate was 13%. Of the PDA/reader units, 55% needed repair within
      1 year. CONCLUSIONS: The analytical performance showed high precision and good
      correlation with the Nova and i-STAT platforms. Test card and instrument failure
      rates were higher than that of the i-STAT system.

PMID- 24124153
TI  - Clinicolaboratory study of mother-to-neonate transmission of hepatitis E virus in
      Egypt.
AB  - OBJECTIVES: To study the presence of hepatitis E viremia in neonates with
      congenital infections. METHODS: We included 29 neonates with clinical signs and
      symptoms suggesting congenital infections, along with their mothers. The control
      group comprised 29 healthy neonates and their mothers. Laboratory evaluations
      were performed for each sample for liver function profiles and virological
      studies for hepatitis viruses B, C, and E. RESULTS: The most common viral markers
      in mothers were for hepatitis C immunoglobulin G (IgG) (41%), followed by
      hepatitis B surface antigen (34%) and hepatitis E virus (HEV) IgG (31%). The most
      common presentations in neonates were respiratory distress syndrome, followed by
      preterm birth and signs of sepsis (both 41%) and hepatosplenomegaly (13%).
      CONCLUSIONS: This study highlights the occurrence of HEV infection among other
      etiological conditions causing congenital infections. Vertical transmission from
      mothers was common in our patients. Although HEV ran a milder course, more
      studies are needed.

PMID- 24124154
TI  - Immunophenotypic characterization of T-cell prolymphocytic leukemia.
AB  - OBJECTIVES: To review clinical data, cytogenetic findings, and flow cytometric
      analysis in 20 patients with T-cell prolymphocytic leukemia (T-PLL), a rare,
      aggressive, mature T-cell leukemia with poor prognosis and short survival.
      METHODS: Using multiparameter flow cytometry with a large combination of
      antibodies, we summarize the immunophenotypic features of T-PLL, including
      unusual immunophenotypic variants, and illustrate immunophenotypic clues that may
      help distinguish this entity from other T-cell malignancies. RESULTS: By flow
      cytometry, T-PLL is characterized by a postthymic mature T-cell immunophenotype
      with a variety of abnormalities that usually allow distinction from other mature
      T-cell leukemias. CONCLUSIONS: Although definitive diagnosis of T-PLL requires a
      systemic approach with integration of clinical data, morphology, immunophenotype,
      cytogenetics/fluorescence in situ hybridization, and molecular features, our
      results indicate immunophenotyping by multiparameter flow cytometry greatly
      facilitates diagnosis and assists with subclassification of this mature T-cell
      leukemia.

PMID- 24124155
TI  - Ultrasensitive RNA in situ hybridization for detection of restricted clonal
      expression of low-abundance immunoglobulin light chain mRNA in B-cell
      lymphoproliferative disorders.
AB  - OBJECTIVES: To assess the feasibility of using a novel ultrasensitive bright
      field in situ hybridization approach (BRISH) to evaluate kappa and lambda
      immunoglobulin messenger RNA (mRNA) expression in situ in B-cell non-Hodgkin
      lymphoma (NHL). METHODS: A series of 110 semiconsecutive clinical cases evaluated
      for lymphoma with historic flow cytometric (FCM) results were assessed with
      BRISH. RESULTS: BRISH light chain restriction (LCR) results were concordant with
      FCM in 108 (99%) of 109 evaluable cases. Additional small B-cell lymphoma cohorts
      were successfully evaluated. CONCLUSIONS: BRISH analysis of kappa and lambda
      immunoglobulin mRNA expression is a sensitive tool for establishing LCR in B-cell
      NHL when FCM results are not available.

PMID- 24124156
TI  - Comparison of automated platelet counts and potential effect on transfusion
      decisions in cancer patients.
AB  - OBJECTIVES: To evaluate the accuracy of platelet counts from various hematology
      analyzers using a reference immunologic method. METHODS: We tested 403 samples
      with platelet counts less than 50 * 10(9)/L with the Advia (Siemens, Tarrytown,
      NY), Sysmex (Mundelein, IL), and Abbott (Santa Clara, CA) analyzers. RESULTS: All
      methods showed a positive bias, especially at less than 20 * 10(9)/L and less
      than 10 * 10(9)/L. Undertransfusion risk ranged from 9.1% to 43.3 % in the groups
      below 20 * 10(9)/L and below 10 * 10(9)/L, respectively. For patients with
      optical counts more than 10 * 10(9)/L and CD61 less than 10 * 10(9)/L, 64.5% were
      transfused within 24 hours of the reported count, while 35.5% were transfused in
      more than 24 hours, after a subsequent optical platelet count of 10 * 10(9)/L or
      less was reported. CONCLUSIONS: Although optical and impedance methods were shown
      to be falsely increased in severely thrombocytopenic samples, further studies are
      needed to determine if more accurate methods would be clinically useful.

PMID- 24124158
TI  - Value based pricing: can it work?

PMID- 24124159
TI  - Ultra scale-down device to predict dewatering levels of solids recovered in a
      continuous scroll decanter centrifuge.
AB  - During centrifugation operation, the major challenge in the recovery of
      extracellular proteins is the removal of the maximum liquid entrapped within the
      spaces between the settled solids-dewatering level. The ability of the scroll
      decanter centrifuge (SDC) to process continuously large amounts of feed material
      with high concentration of solids without the need for resuspension of feeds, and
      also to achieve relatively high dewatering, could be of great benefit for future
      use in the biopharmaceutical industry. However, for reliable prediction of
      dewatering in such a centrifuge, tests using the same kind of equipment at pilot
      scale are required, which are time consuming and costly. To alleviate the need of
      pilot-scale trials, a novel USD device, with reduced amounts of feed (2 mL) and
      to be used in the laboratory, was developed to predict the dewatering levels of a
      SDC. To verify USD device, dewatering levels achieved were plotted against
      equivalent compression (Gtcomp ) and decanting (Gtdec ) times, obtained from
      scroll rates and feed flow rates operated at pilot-scale, respectively. The USD
      device was able to successfully match dewatering trends of the pilot-scale as a
      function of both Gtcomp and Gtdec , particularly for high cell density feeds,
      hence accounting for all key variables that influenced dewatering in a SDC. In
      addition, it accurately mimicked the maximum dewatering performance of the pilot
      scale equipment. Therefore the USD device has the potential to be a useful tool
      at early stages of process development to gather performance data in the
      laboratory thus minimizing lengthy and costly runs with pilot-scale SDC.

PMID- 24124160
TI  - Associations of maternal pre-pregnancy and gestational body size with offspring
      longitudinal change in BMI.
AB  - OBJECTIVES: Studies demonstrate associations between changes in obesity-related
      phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI)
      and gestational weight gain (GWG) may be associated with adult offspring
      adiposity, no study has examined associations with obesity changes. Associations
      of mppBMI and GWG with longitudinal change in offspring's BMI (DeltaBMI) were
      examined, and whether associations are explained by offspring genetics was
      assessed. METHODS: A birth cohort of 1400 adults, with data at birth, age 17 and
      32 years was used. After genotyping offspring, genetic scores, predictive of
      exposures and outcome were created, and linear regression models with and without
      scores were fit to examine the associations of mppBMI and GWG with DeltaBMI.
      RESULTS: A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75
      kg/m2 increase in DeltaBMI, respectively. The association between mppBMI and
      offspring DeltaBMI was slightly attenuated (12%) with the addition of genetic
      scores. In the GWG model, a significant substantial 28.2% decrease in the
      coefficient was observed. CONCLUSIONS: This study points to an association
      between maternal excess weight in pregnancy and offspring BMI change from
      adolescence to adulthood. Genetic factors may account, in part, for GWG/DeltaBMI
      association. These findings broaden observations that maternal obesity-related
      phenotypes have long-term consequences for offspring health.

PMID- 24124162
TI  - New technologies for single-site robotic surgery in hepato-biliary-pancreatic
      surgery.
AB  - Laparoendoscopic single-site surgery (LESS) aims to reduce incision-related
      complications by using a single surgical access through which multiple
      instruments are inserted simultaneously. First descriptions of LESS procedures
      date back to the early 90 s, but the approach initially failed to gain popularity
      because of technical challenges that markedly impair the principles of
      laparoscopic ergonomics. In recent years LESS has been increasingly applied to
      hepatobiliary procedures including cholecystectomies and liver resections.
      However, the uptake of LESS in hepatobiliary is limited. The surgical robotic
      platform might play a fundamental role in facilitating the uptake of LESS by the
      surgical community since robotic science made it possible to develop adequate
      technology to deal with some of the LESS issues such as restoring surgical
      triangulation. In this paper the current state-of-the-art for robotic LESS
      applied to the hepatobiliary system and emerging technologies enabling safer LESS
      procedures have been reviewed and future perspectives commented on the light of
      our experience.

PMID- 24124161
TI  - Shifts in the vascular endothelial growth factor isoforms result in transcriptome
      changes correlated with early neural stem cell proliferation and differentiation
      in mouse forebrain.
AB  - Regulation of neural stem cell (NSC) fate decisions is critical during the
      transition from a multicellular mammalian forebrain neuroepithelium to the
      multilayered neocortex. Forebrain development requires coordinated vascular
      investment alongside NSC differentiation. Vascular endothelial growth factor A
      (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms
      regulate a broad range of effects in neurovascular systems. To test the
      hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal
      forebrain development, we analyzed the forebrain transcriptome of mice expressing
      specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188.
      Transcriptome analysis identified differentially expressed genes in embryonic day
      (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and
      vascular investment in the telencephalon. Meta-analysis identified gene pathways
      linked to chromosome-level modifications, cell fate regulation, and neurogenesis
      that were altered in Vegf isoform mice. Based on these gene network shifts, we
      predicted that NSC populations would be affected in later stages of forebrain
      development. In the E11.5 telencephalon, we quantified mitotic cells [Phospho
      Histone H3 (pHH3)-positive] and intermediate progenitor cells (Tbr2/Eomes
      positive), observing quantitative and qualitative shifts in these populations. We
      observed qualitative shifts in cortical layering at P0, particularly with Ctip2
      positive cells in layer V. The results identify a suite of genes and functional
      gene networks that can be used to further dissect the role of Vegf in regulating
      NSC differentiation and downstream consequences for NSC fate decisions.

PMID- 24124164
TI  - Proteomic snapshot of spearmint (Mentha spicata L.) leaf trichomes: a genuine
      terpenoid factory.
AB  - Peltate glandular trichomes from Mentha spicata were purified on a Percoll
      gradient and soluble and membrane proteins were trypsinized and the peptides were
      separated by nano-LC fractionation and analyzed by MALDI-MS/MS. The vast majority
      of the 1666 proteins identified were housekeeping proteins or involved in the
      primary metabolism. However, 57 were predicted to be involved in the secondary
      metabolism. Of these, 21 were involved in the synthesis of phenylpropanoids and
      phenolics and 32 in terpenoid synthesis. Of the 14 membrane transporters
      identified, the 11 ATP-binding cassette transporters provide good material for
      assessing whether active transport is required for the transfer of monoterpenoid
      intermediates between cellular compartments and for the secretion of the final
      products into the subcuticular storage cavity. In conclusion, this proteome
      analysis of M. spicata peltate trichomes has identified several candidate
      proteins that might be involved in terpenoid synthesis and transport. The data
      have been deposited to the ProteomeXchange with identifier PXD000352
      (http://proteomecentral.proteomexchange.org/dataset/PXD000352). 

PMID- 24124165
TI  - Promotion of Forster resonance energy transfer in a saponite clay containing
      luminescent polyhedral oligomeric silsesquioxane and rhodamine dye.
AB  - A new hybrid photostable saponite clay with embedded donor-acceptor dyes was
      prepared and characterized in this work. The saponite is intercalated with a
      luminescent polyhedral oligomeric silsesquioxane, which transfers the
      photoexcitation energy directly to an acceptor dye (rhodamine B). The obtained
      composite material was characterized by means of XRD, TEM microscopy, and UV/Vis
      and photoluminescence spectroscopy. A physicochemical study showed that the
      system behaved as an efficient Forster resonance energy transfer pair, owing to
      the very good spectral overlap of donor emission (lambdaem =510-540 nm) and
      acceptor absorption in the lambda=530-570 nm range. The hybrid material
      represents the first example of a photonic antenna based on a synthetic saponite
      clay and can be considered a step forward in the search for new, efficient, and
      stable materials suitable for light-harvesting applications.

PMID- 24124163
TI  - Association between endogenous sex steroid hormones and inflammatory biomarkers
      in US men.
AB  - Sex steroid hormones and inflammatory biomarkers are both associated with the
      development and progression of chronic diseases, but their interrelationship is
      relatively uncharacterized. We examined the association of sex hormones and sex
      hormone-binding globulin (SHBG) with biomarkers of inflammation, C-reactive
      protein (CRP) and white blood cell (WBC) count. The study included data from 809
      adult men in the National Health and Nutrition Examination Survey 1999-2004.
      Geometric means and 95% confidence intervals were estimated separately for CRP
      and WBC concentrations by sex steroid hormones and SHBG using weighted linear
      regression models. Higher concentrations of total (slope per one quintile in
      concentration, -0.18; p-trend, 0.001) and calculated free (slope, -0.13; p-trend,
      0.03) testosterone were statistically significantly associated with lower
      concentrations of CRP, but not with WBC count. Men in the bottom quintile of
      total testosterone (<=3.3 ng/mL), who might be considered to have clinically low
      testosterone, were more likely to have elevated CRP (>=3 mg/L) compared with men
      in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated
      free estradiol (E2) were positively associated with both CRP (Total E2: slope,
      0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2:
      slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations.
      SHBG concentrations were inversely associated with WBC count (slope, -0.03; p
      trend, 0.04), but not with CRP. These cross-sectional findings are consistent
      with the hypothesis that higher androgen and lower oestrogen concentrations may
      have an anti-inflammatory effect in men. 

PMID- 24124166
TI  - Continuous cultivation of human hamstring tenocytes on microcarriers in a spinner
      flask bioreactor system.
AB  - Tendon healing is a time consuming process leading to the formation of a
      functionally altered reparative tissue. Tissue engineering-based tendon
      reconstruction is attracting more and more interest. The aim of this study was to
      establish tenocyte expansion on microcarriers in continuous bioreactor cultures
      and to study tenocyte behavior during this new approach. Human hamstring tendon
      derived tenocytes were expanded in monolayer culture before being seeded at two
      different seeding densities (2.00 and 4.00 3 106 cells/1000 cm2 surface) on
      CytodexTM type 3 microcarriers. Tenocytes' vitality, growth kinetics and glucose/
      lactic acid metabolism were determined dependent on the seeding densities and
      stirring velocities (20 or 40 rpm) in a spinner flask bioreactor over a period of
      2 weeks. Gene expression profiles of tendon extracellular matrix (ECM) markers
      (type I/III collagen, decorin, cartilage oligomeric protein [COMP], aggrecan) and
      the tendon marker scleraxis were analyzed using real time detection polymerase
      chain reaction (RTD-PCR). Type I collagen and decorin deposition was demonstrated
      applying immunolabeling. Tenocytes adhered on the carriers, remained vital,
      proliferated and revealed an increasing glucose consumption and lactic acid
      formation under all culture conditions. "Bead-to-bead" transfer of cells from one
      microcarrier to another, a prerequisite for continuous tenocyte expansion, was
      demonstrated by scanning electron microscopy. Type I and type III collagen gene
      expression was mainly unaffected, whereas aggrecan and partly also decorin and
      COMP expression was significantly downregulated compared to monolayer cultures.
      Scleraxis gene expression revealed no significant regulation on the carriers. In
      conclusion, tenocytes could be successfully expanded on microcarriers. Therefore,
      bioreactors are promising tools for continuous tenocyte expansion.

PMID- 24124167
TI  - Validity and concordance between self-reported and clinical diagnosis of
      hypertension among elderly residents in northeastern Brazil.
AB  - BACKGROUND: Self-reported information has been used as an easy and quick method
      to estimate the prevalence of systemic hypertension in populations. However,
      verification of whether self-reports of the disease are consistent with clinical
      diagnosis is essential for proper use of this information. This study aimed to
      verify the validity and concordance between self-reported and clinical diagnosis
      of hypertension in the elderly population of a city in northeastern Brazil.
      METHODS: This was a cross-sectional and population-based study. The prevalence of
      diagnosed and self-reported hypertension and the validity and concordance between
      self-reported and clinical diagnosis and their distribution according to
      demographic and socioeconomic variables were assessed. The validity of self
      reported hypertension was determined by sensitivity, specificity, and positive
      and negative predictive value. RESULTS: Overall, 795 elderly patients were
      evaluated (69.1% women). There was a high prevalence of hypertension among the
      elderly (diagnosed: 75.1%, 95% confidence interval (CI) = 71.1%-77.9%; self
      reported: 59.7%, 95% CI = 56.3%-63.1%). For self-reported hypertension,
      sensitivity was substantial (77.1%), specificity was excellent (93.4%), positive
      predictive value was excellent (97.3%), and negative predictive value was
      moderate (57.2%). There was a moderate concordance between self-reported and
      clinical diagnosis of hypertension (kappa = 0.59; P < 0.001). CONCLUSIONS:
      Reasonable validity and moderate concordance of self-reported information on
      hypertension was observed, which reinforces the idea that this information can be
      used as strategy for detecting the disease prevalence in this population.
      However, because of nonachievement of excellence in the validity and reliability
      of the measured blood pressure, this information should be carefully considered
      for the strategic planning of health services.

PMID- 24124168
TI  - Purification of tropomyosin Br-3 and 5NM1 and characterization of their
      interactions with actin.
AB  - Tropomyosins were first identified in neuronal systems in 1973. Although numerous
      isoforms were found and described since then, many aspects of their function and
      interactions remained unknown. Tropomyosin isoforms show different sorting
      pattern in neurogenesis. As one example, TM5NM1/2 is present in developing axons,
      but it is replaced by TMBr-3 in mature neurons, suggesting that these tropomyosin
      isoforms contribute differently to the establishment of the functional features
      of the neuronal actin networks. We developed a method for the efficient
      purification of TMBr-3 and TM5NM1 as recombinant proteins using bacterial
      expression system and investigated their interactions with actin. We found that
      both isoforms bind actin filaments, however, the binding of TM5NM1 was much
      stronger than that of TMBr-3. TMBr-3 and TM5NM1 modestly affected actin assembly
      kinetics, in an opposite manner. Consistently with the higher affinity of TM5NM1
      it inhibited actin filament disassembly more efficiently than TMBr-3. Similarly
      to other previously studied tropomyosins TM5NM1 inhibited the Arp2/3 complex
      mediated actin assembly. Notably, TMBr-3 did not influence the Arp2/3 complex
      mediated polymerization. This is a unique feature of TMBr-3, since so far it is
      the only known tropomyosin supporting the activity of the Arp2/3 complex,
      indicating that TMBr-3 may colocalize and work simultaneously with Arp2/3 complex
      in neuronal cells.

PMID- 24124169
TI  - Use of cell type-specific transcriptome to identify genes specifically involved
      in Muller glia differentiation during retinal development.
AB  - Retinal progenitor cells alter their properties over the course of development,
      and sequentially produce different sub-populations of retinal cells. We had
      previously found that early and late retinal progenitor cell populations can be
      distinguished by their surface antigens, SSEA-1 and c-kit, respectively. Using
      DNA microarray analysis, we examined the transcriptomes of SSEA-1 positive cells
      at E14, and c-kit positive, and c-kit negative cells at P1. By comparing data, we
      identified genes specifically expressed in c-kit positive late retinal progenitor
      cells. The previous literature suggests that most of the c-kit positive cell
      specific genes are related to glia differentiation in brain or are expressed in
      Muller glia. Since Notch signaling promotes Muller glia differentiation in
      retina, we examined the effects of gain- and loss-of-Notch signaling on
      expression of these genes and found that all the genes were positively affected
      by Notch signaling. Finally, we screened the genes for their function in retinal
      development by shRNA-based suppression in retinal explants. In about half the
      genes, Muller glia differentiation was perturbed when their expression was
      suppressed. Taken together, these results show that at P1, c-kit positive retinal
      progenitor cells, which include Muller glia precursor cells, are enriched for
      genes related to glial differentiation. We propose analysis of purified subsets
      of retinal cells as a powerful tool to elucidate the molecular basis of retinal
      development.

PMID- 24124170
TI  - Physical exam and ultrasound characteristics of right varicocoeles in adolescents
      with left varicocoeles.
AB  - The published incidence of bilateral varicocoeles in adults is much higher than
      among adolescents. We investigated our adolescent varicocoele database to
      determine (i) the presence of subclinical and palpable right varicocoele s in
      boys with a left varicocoele, (ii) the effect, if any, of right varicocoele on
      asymmetry measurements and (iii) the difference in duplex doppler ultrasound
      (DDUS) findings between left varicocoele s and contralateral right varicocoele s.
      Among 506 boys with a known left varicocoele who underwent DDUS, the incidence of
      right clinical and subclinical varicocoele s as well as the influence of Tanner
      stage, varicocoele grade, laterality, peak retrograde flow (PRF) and maximum vein
      diameter (MVD) on testicular volume and asymmetry was examined using univariate
      and multivariate linear regression. Right retrograde flow was detected in 204 of
      506 (40.3%) boys. Varicocoele grades were subclinical in 89 (18%), grade I in 51
      (10%), grade II in 63 (12%) and grade III in 1 (0.2%). In patients with
      bilaterally palpable varicocoele s, increasing left grade was associated with
      greater testicular asymmetry (p = 0.02) and increasing right grade was associated
      with less testicular asymmetry (p = 0.01). Mean PRF and MVD values were lower in
      right as compared to left varicocoele s. Contrary to common perception, both
      subclinical and palpable right varicocoele s are frequently associated with left
      varicocoele s in adolescents. Although the contribution of right varicocoele s to
      fertility is controversial, these right varicocoele s can influence clinically
      relevant parameters, particularly testicular asymmetry, and thus influence which
      left varicocoele s undergo surgery. 

PMID- 24124171
TI  - Fe(OTf)3-catalyzed alpha-benzylation of aryl methyl ketones with electrophilic
      secondary and aryl alcohols.
AB  - Acid-catalyzed Friedel-Crafts alkylation of 1,3-dicarbonyl compounds with
      electrophilic alcohols, is known to be an effective C-C bond forming reaction.
      However, until now, this reaction has not been amenable for alpha-alkylation of
      aryl methyl ketones because of the notoriously low nucleophilicities of these
      compounds. Therefore, alpha-alkylation of aryl methyl ketone relies on precious
      metal catalysts and also, the use of primary alcohols is mandatory. In this
      study, we found that a system composed of a Fe(OTf)3 catalyst and chlorobenzene
      solvent is sufficient to promote the title Friedel-Crafts reaction by using
      benzhydrols as electrophiles. 3,4-Dihydro-9-(2-hydroxy-4,4-dimethyl-6-oxo-1
      cyclohexen-1-yl)-3,3-dimethyl-xanthen-1(2H)-one was also applicable as an
      electrophile in this type of benzylation reaction. On the basis of this result, a
      three-component reaction of salicylaldehyde, dimedone, and aryl methyl ketone was
      also developed, and this provided an efficient way for the synthesis of densely
      substituted 4H-chromene derivatives.

PMID- 24124172
TI  - Enveloped virus inactivation using neutral arginine solutions and applications in
      therapeutic protein purification processes.
AB  - For the manufacturing of recombinant protein therapeutics produced from mammalian
      cell culture, demonstrating the capacity of the purification process to
      effectively clear infectious viruses is a regulatory requirement. At least two
      process steps, using different mechanisms of virus removal and/or inactivation,
      should be validated in support of the regulatory approval process. For example,
      exposure of the product stream to low pH, detergents or solvent/detergent
      combinations is commonly incorporated in protein purification processes for the
      inactivation of lipid-enveloped viruses. However, some proteins have limited
      stability at low pH or in the presence of the detergents, and alternative
      techniques for achieving the inactivation of enveloped viruses would be
      beneficial. We present here an alternative and novel approach for the rapid
      inactivation of enveloped viruses using pH-neutral buffer solutions containing
      arginine. The implementation of this approach in a monoclonal antibody or Fc
      fusion protein purification process is described and illustrated with several
      different therapeutic proteins. The use of the neutral pH arginine solution was
      able to effectively inactivate two enveloped model viruses, with no measurable
      effect on the product quality of the investigated proteins. Thus, the use of pH
      neutral arginine containing buffer solutions provides an alternative means of
      virus inactivation where other forms of virus inactivation, such as low pH and/or
      solvent/detergent treatments are not possible or undesirable due to protein
      stability limitations.

PMID- 24124173
TI  - Maine allows importation of mail order prescription drugs.

PMID- 24124174
TI  - Most British non-white groups are less healthy than white people, census data
      show.

PMID- 24124176
TI  - Randomised controlled trial of whether erotic material is required for semen
      collection: impact of informed consent on outcome.
AB  - Semen is collected to evaluate male fertility or cryostore sperm preferentially
      in laboratories but such collection facilities have no standard fit-out. It is
      widely believed but untested whether providing erotic material (EM) is required
      to collect semen by masturbation in the unfamiliar environment. To test this
      assumption, 1520 men (1046 undergoing fertility evaluation, 474 sperm
      cryostorage, providing 1932 semen collection episodes) consecutively attending
      the semen laboratory of a major metropolitan teaching hospital for semen analysis
      were eligible for randomization to be provided or not with printed erotic
      material EM (X-rated, soft-core magazines) during semen collection. Randomization
      was performed by providing magazines in the collection rooms (as a variation on
      non-standard fit-out) on alternate weeks using a schedule concealed from
      participants. In the pilot study, men were randomized without seeking consent. In
      the second part of the study, which continued on from the first without
      interruption, an approved informed consent procedure was added. The primary
      outcome, the time to collect semen defined as the time from receiving to
      returning the sample receptacle, was significantly longer (by ~6%, 14.9 +/- 0.3
      [mean +/- standard error of mean] vs. 14.0 +/- 0.2 minutes, p = 0.02) among men
      provided with EM than those randomized to not being provided. There was no
      significant increase in the failure to collect semen samples (2.6% overall) nor
      any difference in age, semen volume or sperm concentration, output or motility
      according to whether EM was provided or not. The significantly longer time to
      collect was evident in the pilot study and the study overall, but not in the main
      study where the informed consent procedure was used. This study provides evidence
      that refutes the assumption that EM needs to be provided for semen collection in
      a laboratory. It also provides an example of a usually unobservable participation
      bias influencing study outcome of a randomized controlled trials. 

PMID- 24124175
TI  - The Chlamydomonas mutant pf27 reveals novel features of ciliary radial spoke
      assembly.
AB  - To address the mechanisms of ciliary radial spoke assembly, we took advantage of
      the Chlamydomonas pf27 mutant. The radial spokes that assemble in pf27 are
      localized to the proximal quarter of the axoneme, but otherwise are fully
      assembled into 20S radial spoke complexes competent to bind spokeless axonemes in
      vitro. Thus, pf27 is not defective in radial spoke assembly or docking to the
      axoneme. Rather, our results suggest that pf27 is defective in the transport of
      spoke complexes. During ciliary regeneration in pf27, radial spoke assembly
      occurs asynchronously from other axonemal components. In contrast, during ciliary
      regeneration in wild-type Chlamydomonas, radial spokes and other axonemal
      components assemble concurrently as the axoneme grows. Complementation in
      temporary dikaryons between wild-type and pf27 reveals rescue of radial spoke
      assembly that begins at the distal tip, allowing further assembly to proceed from
      tip to base of the axoneme. Notably, rescued assembly of radial spokes occurred
      independently of the established proximal radial spokes in pf27 axonemes in
      dikaryons. These results reveal that 20S radial spokes can assemble proximally in
      the pf27 cilium but as the cilium lengthens, spoke assembly requires transport.
      We postulate that PF27 encodes an adaptor or modifier protein required for radial
      spoke-IFT interaction.

PMID- 24124178
TI  - Triazole-substituted nitroarene derivatives: synthesis, characterization, and
      energetic studies.
AB  - A series of dense and energetic polynitroaryl-1,2,4-triazoles were synthesized
      through the nitration of aryl-1,2,4-triazoles. The Cu-catalyzed/base-mediated
      coupling reactions of haloarenes with 1,2,4-triazoles delivered N-aryl-1,2,4
      triazoles. These new nitro-rich-aryltriazoles were characterized by analytical
      and spectroscopic methods. The solid-state structures of most of these compounds
      were established by X-ray diffraction analysis. Their thermal properties were
      determined by differential scanning calorimetry-thermogravimetric analysis. Their
      heats of formation (HOFs) and crystal densities were also calculated. The
      densities of the synthesized compounds ranged from 1.40 to 1.85 g cm(-3). Some of
      these newly synthesized compounds exhibited high positive HOFs, good thermal
      stabilities, high densities, and reasonable detonation velocities and pressures.

PMID- 24124177
TI  - Urea enhances cell growth and pyruvate production in Torulopsis glabrata.
AB  - Torulopsis glabrata is a strain of yeast that is used for the industrial
      production of pyruvate. Determination of the optimal nutrient environment is
      vital for obtaining the most efficient production system. In this study, the
      fermentation parameters, gene transcription levels, activities of key enzymes and
      metabolites levels were analyzed when either urea or ammonium chloride was used
      as the sole source of nitrogen. Urea caused an increase in the dry cell weight
      (18%) and pyruvate productivity was significantly increased (14%). The
      transcription levels of CAGL0M05533g (DUR1,2), CAGL0J07612g (ZWF1), and
      CAGL0I02200g (SOL3) were upregulated, but CAGL0G05698g (GDH2) and CAGL0L01089g
      (GLT1) were down-regulated. The activities of urea amidolyase, NADPH dependent
      glutamate dehydrogenase and glucose-6-phosphate dehydrogenase were increased by
      380, 430, and 140%, respectively. The activities of arginase and glutamate
      synthase were decreased by 40 and 35%, respectively. The NADPH content was
      increased by 33%, whilst ATP content was decreased by 37%. This changed the
      intracellular levels of organic acids and amino acids. The results expand the
      understanding of the physiological characteristics of yeast species grown with
      different sources of nitrogen.

PMID- 24124179
TI  - Herbal products are often contaminated, study finds.

PMID- 24124180
TI  - Development of a scale down cell culture model using multivariate analysis as a
      qualification tool.
AB  - In characterizing a cell culture process to support regulatory activities such as
      process validation and Quality by Design, developing a representative scale down
      model for design space definition is of great importance. The manufacturing
      bioreactor should ideally reproduce bench scale performance with respect to all
      measurable parameters. However, due to intrinsic geometric differences between
      scales, process performance at manufacturing scale often varies from bench scale
      performance, typically exhibiting differences in parameters such as cell growth,
      protein productivity, and/or dissolved carbon dioxide concentration. Here, we
      describe a case study in which a bench scale cell culture process model is
      developed to mimic historical manufacturing scale performance for a late stage
      CHO-based monoclonal antibody program. Using multivariate analysis (MVA) as
      primary data analysis tool in addition to traditional univariate analysis
      techniques to identify gaps between scales, process adjustments were implemented
      at bench scale resulting in an improved scale down cell culture process model.
      Finally we propose an approach for small scale model qualification including
      three main aspects: MVA, comparison of key physiological rates, and comparison of
      product quality attributes.

PMID- 24124182
TI  - Most sore throats in US are still treated with antibiotics.

PMID- 24124181
TI  - IQGAP1 interactome analysis by in vitro reconstitution and live cell 3-color FRET
      microscopy.
AB  - IQGAP1 stimulates branched actin filament nucleation by activating N-WASP, which
      then activates the Arp2/3 complex. N-WASP can be activated by other factors,
      including GTP-bound Cdc42 or Rac1, which also bind IQGAP1. Here we report the use
      of purified proteins for in vitro binding and actin polymerization assays, and
      Forster (or fluorescence) resonance energy transfer (FRET) microscopy of cultured
      cells to illuminate functional interactions among IQGAP1, N-WASP, actin, and
      either Cdc42 or Rac1. In pyrene-actin assembly assays containing N-WASP and
      Arp2/3 complex, IQGAP1 plus either small G protein cooperatively stimulated actin
      filament nucleation by reducing the lag time before 50% maximum actin
      polymerization was reached. Similarly, Cdc42 and Rac1 modulated the binding of
      IQGAP1 to N-WASP in a dose-dependent manner, with Cdc42 enhancing the interaction
      and Rac1 reducing the interaction. These in vitro reconstitution results
      suggested that IQGAP1 interacts by similar, yet distinct mechanisms with Cdc42
      versus Rac1 to regulate actin filament assembly through N-WASP in vivo. The
      physiological relevance of these multi-protein interactions was substantiated by
      3-color FRET microscopy of live MDCK cells expressing various combinations of
      fluorescent N-WASP, IQGAP1, Cdc42, Rac1, and actin. This study also establishes 3
      color FRET microscopy as a powerful tool for studying dynamic intermolecular
      interactions in live cells.

PMID- 24124183
TI  - II. Bringing flow into haemostasis diagnostics.

PMID- 24124184
TI  - A novel approach to assess hemorrhagic shock severity using the arterially
      determined left ventricular isovolumic contraction period.
AB  - Recently, the ventilatory variation in pre-ejection period (DeltaPEP) was found
      to be useful in the prediction of fluid-responsiveness of patients in shock. In
      the present study we investigated the behavior of the ventilation-induced
      variations in the systolic timing intervals in response to a graded hemorrhage
      protocol. The timing intervals studied included the ventilatory variation in
      ventricular electromechanical delay (DeltaEMD), isovolumic contraction period
      (determined from the arterial pressure waveform, DeltaAIC), pulse travel time
      (DeltaPTT), and DeltaPEP. DeltaAIC and DeltaPEP were evaluated in the aorta and
      carotid artery (annotated by subscripts Ao and CA) and were compared with the
      responses of pulse pressure variation (DeltaPPAo) and stroke volume variation
      (DeltaSV). The graded hemorrhage protocol, followed by resuscitation using
      norepinephrine and autologous blood transfusion, was performed in eight
      anesthetized Yorkshire X Landrace swine. DeltaAICAo, DeltaAICCA, DeltaPEPAo,
      DeltaPEPCA, DeltaPPAo, DeltaPPCA, and DeltaSV showed significant increases during
      the graded hemorrhage and significant decreases during the subsequent
      resuscitation. DeltaAICAo, DeltaAICCA, DeltaPEPAo, and DeltaPEPCA all correlated
      well with DeltaPPAo and DeltaSV (all r >= 0.8, all P < 0.001). DeltaEMD and
      DeltaPTT did not significantly change throughout the protocol. In contrast with
      DeltaPEPAo, which was significantly higher than DeltaPEPCA (P < 0.01), DeltaAICAo
      was not different from DeltaAICCA. In conclusion, ventilation-induced preload
      variation principally affects the arterially determined isovolumic contraction
      period (AIC). Moreover, DeltaAIC can be determined solely from the arterial
      pressure waveform, whereas DeltaPEP also requires ECG measurement. Importantly,
      DeltaAIC determined from either the carotid or aortic pressure waveform are
      interchangeable, suggesting that, in contrast with DeltaPEP, DeltaAIC may be site
      independent. 

PMID- 24124185
TI  - Parameter sensitivity analysis of a lumped-parameter model of a chain of
      lymphangions in series.
AB  - Any disruption of the lymphatic system due to trauma or injury can lead to edema.
      There is no effective cure for lymphedema, partly because predictive knowledge of
      lymphatic system reactions to interventions is lacking. A well-developed model of
      the system could greatly improve our understanding of its function. Lymphangions,
      defined as the vessel segment between two valves, are the individual pumping
      units. Based on our previous lumped-parameter model of a chain of lymphangions,
      this study aimed to identify the parameters that affect the system output the
      most using a sensitivity analysis. The system was highly sensitive to minimum
      valve resistance, such that variations in this parameter caused an order-of
      magnitude change in time-average flow rate for certain values of imposed pressure
      difference. Average flow rate doubled when contraction frequency was increased
      within its physiological range. Optimum lymphangion length was found to be some
      13-14.5 diameters. A peak of time-average flow rate occurred when transmural
      pressure was such that the pressure-diameter loop for active contractions was
      centered near maximum passive vessel compliance. Increasing the number of
      lymphangions in the chain improved the pumping in the presence of larger adverse
      pressure differences. For a given pressure difference, the optimal number of
      lymphangions increased with the total vessel length. These results indicate that
      further experiments to estimate valve resistance more accurately are necessary.
      The existence of an optimal value of transmural pressure may provide additional
      guidelines for increasing pumping in areas affected by edema. 

PMID- 24124186
TI  - Cardiac sympathetic innervation and PGP9.5 expression by cardiomyocytes after
      myocardial infarction: effects of central MR blockade.
AB  - Central mechanisms involving mineralocorticoid receptor (MR) activation
      contribute to an increase in sympathetic tone after myocardial infarction (MI).
      We hypothesized that this central mechanism also contributes to cardiac
      sympathetic axonal sprouting and that central MR blockade reduces cardiac
      sympathetic hyperinnervation post-MI. Post-MI, tyrosine hydroxylase (TH) and
      norepinephrine transporter protein content in the noninfarcted base of the heart
      remained unaltered. In contrast, protein gene product (PGP)9.5 protein was
      increased twofold in the base of the heart and sixfold in the peri-infarct area
      at 1 wk post-MI and was associated with increased ubiquitin expression. These
      changes persisted to a lesser extent at 4 wk post-MI and were no longer present
      at 12 wk. Cardiac myocytes rather than sympathetic axons were the main source of
      this elevated PGP9.5 expression. At 7-10 days post-MI, in the peri-infarct area,
      sympathetic hyperinnervation was observed with a fourfold increase in growth
      associated protein 43, a twofold increase in TH, and a 50% increase in PGP9.5
      positive fibers compared with the epicardial side of the left ventricle in sham
      rats. Central infusion of the MR blocker eplerenone markedly attenuated these
      increases in nerve densities but did not affect overall cardiac PGP9.5 and
      ubiquitin protein overexpression. We conclude that central MR activation
      contributes to sympathetic hyperinnervation, possibly by decreasing cardiac
      sympathetic activity post-MI, or by affecting other mechanisms, such as the
      expression of nerve growth factor. Marked PGP9.5 expression occurs in
      cardiomyocytes early post-MI, which may contribute to the increase in ubiquitin. 

PMID- 24124187
TI  - Discharge of RVLM vasomotor neurons is not increased in anesthetized angiotensin
      II-salt hypertensive rats.
AB  - Neurons of the rostral ventrolateral medulla (RVLM) are critical for generating
      and regulating sympathetic nerve activity (SNA). Systemic administration of ANG
      II combined with a high-salt diet induces hypertension that is postulated to
      involve elevated SNA. However, a functional role for RVLM vasomotor neurons in
      ANG II-salt hypertension has not been established. Here we tested the hypothesis
      that RVLM vasomotor neurons have exaggerated resting discharge in rats with ANG
      II-salt hypertension. Rats in the hypertensive (HT) group consumed a high-salt
      (2% NaCl) diet and received an infusion of ANG II (150 ng.kg(-1).min(-1) sc) for
      14 days. Rats in the normotensive (NT) group consumed a normal salt (0.4% NaCl)
      diet and were infused with normal saline. Telemetric recordings in conscious rats
      revealed that mean arterial pressure (MAP) was significantly increased in HT
      compared with NT rats (P < 0.001). Under anesthesia (urethane/chloralose), MAP
      remained elevated in HT compared with NT rats (P < 0.01). Extracellular single
      unit recordings in HT (n = 28) and NT (n = 22) rats revealed that barosensitive
      RVLM neurons in both groups (HT, 23 cells; NT, 34 cells) had similar cardiac
      rhythmicity and resting discharge. However, a greater (P < 0.01) increase of MAP
      was needed to silence discharge of neurons in HT (17 cells, 44 +/- 5 mmHg) than
      in NT (28 cells, 29 +/- 3 mmHg) rats. Maximum firing rates during arterial
      baroreceptor unloading were similar across groups. We conclude that heightened
      resting discharge of sympathoexcitatory RVLM neurons is not required for
      maintenance of neurogenic ANG II-salt hypertension. 

PMID- 24124188
TI  - Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation
      and Ca2+-induced ATP production in cardiac H9c2 myoblasts.
AB  - Ca(+) influx to mitochondria is an important trigger for both mitochondrial
      dynamics and ATP generation in various cell types, including cardiac cells.
      Mitochondrial Ca(2+) influx is mainly mediated by the mitochondrial Ca(2+)
      uniporter (MCU). Growing evidence also indicates that mitochondrial Ca(2+) influx
      mechanisms are regulated not solely by MCU but also by multiple
      channels/transporters. We have previously reported that skeletal muscle-type
      ryanodine receptor (RyR) type 1 (RyR1), which expressed at the mitochondrial
      inner membrane, serves as an additional Ca(2+) uptake pathway in cardiomyocytes.
      However, it is still unclear which mitochondrial Ca(2+) influx mechanism is the
      dominant regulator of mitochondrial morphology/dynamics and energetics in
      cardiomyocytes. To investigate the role of mitochondrial RyR1 in the regulation
      of mitochondrial morphology/function in cardiac cells, RyR1 was transiently or
      stably overexpressed in cardiac H9c2 myoblasts. We found that overexpressed RyR1
      was partially localized in mitochondria as observed using both immunoblots of
      mitochondrial fractionation and confocal microscopy, whereas RyR2, the main RyR
      isoform in the cardiac sarcoplasmic reticulum, did not show any expression at
      mitochondria. Interestingly, overexpression of RyR1 but not MCU or RyR2 resulted
      in mitochondrial fragmentation. These fragmented mitochondria showed bigger and
      sustained mitochondrial Ca(2+) transients compared with basal tubular
      mitochondria. In addition, RyR1-overexpressing cells had a higher mitochondrial
      ATP concentration under basal conditions and showed more ATP production in
      response to cytosolic Ca(2+) elevation compared with nontransfected cells as
      observed by a matrix-targeted ATP biosensor. These results indicate that RyR1
      possesses a mitochondrial targeting/retention signal and modulates mitochondrial
      morphology and Ca(2+)-induced ATP production in cardiac H9c2 myoblasts. 

PMID- 24124189
TI  - Pulmonary artery endothelial cell dysfunction and decreased populations of highly
      proliferative endothelial cells in experimental congenital diaphragmatic hernia.
AB  - Decreased lung vascular growth and pulmonary hypertension contribute to poor
      outcomes in congenital diaphragmatic hernia (CDH). Mechanisms that impair
      angiogenesis in CDH are poorly understood. We hypothesize that decreased vessel
      growth in CDH is caused by pulmonary artery endothelial cell (PAEC) dysfunction
      with loss of a highly proliferative population of PAECs (HP-PAEC). PAECs were
      harvested from near-term fetal sheep that underwent surgical disruption of the
      diaphragm at 60-70 days gestational age. Highly proliferative potential was
      measured via single cell assay. PAEC function was assessed by assays of growth
      and tube formation and response to known proangiogenic stimuli, vascular
      endothelial growth factor (VEGF), and nitric oxide (NO). Western blot analysis
      was used to measure content of angiogenic proteins, and superoxide production was
      assessed. By single cell assay, the proportion of HP-PAEC with growth of >1,000
      cells was markedly reduced in the CDH PAEC, from 29% (controls) to 1% (CDH) (P <
      0.0001). Compared with controls, CDH PAEC growth and tube formation were
      decreased by 31% (P = 0.012) and 54% (P < 0.001), respectively. VEGF and NO
      treatments increased CDH PAEC growth and tube formation. VEGF and VEGF-R2
      proteins were increased in CDH PAEC; however, eNOS and extracellular superoxide
      dismutase proteins were decreased by 29 and 88%, respectively. We conclude that
      surgically induced CDH in fetal sheep causes endothelial dysfunction and marked
      reduction of the HP-PAEC population. We speculate that this CDH PAEC phenotype
      contributes to impaired vascular growth in CDH. 

PMID- 24124192
TI  - Is EM dead?
AB  - Since electron microscopy (EM) first appeared in the 1930s, it has held centre
      stage as the primary tool for the exploration of biological structure. Yet, with
      the recent developments of light microscopy techniques that overcome the
      limitations imposed by the diffraction boundary, the question arises as to
      whether the importance of EM in on the wane. This Commentary describes some of
      the pioneering studies that have shaped our understanding of cell structure.
      These include the development of cryo-EM techniques that have given researchers
      the ability to capture images of native structures and at the molecular level. It
      also describes how a number of recent developments significantly increase the
      ability of EM to visualise biological systems across a range of length scales,
      and in 3D, ensuring that EM will remain at the forefront of biology research for
      the foreseeable future. 

PMID- 24124190
TI  - Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to
      treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures.
AB  - The epithelial sodium channel (ENaC) is responsible for Na(+) and fluid
      absorption across colon, kidney, and airway epithelia. Short palate lung and
      nasal epithelial clone 1 (SPLUNC1) is a secreted, innate defense protein and an
      autocrine inhibitor of ENaC that is highly expressed in airway epithelia. While
      SPLUNC1 has a bactericidal permeability-increasing protein (BPI)-type structure,
      its NH2-terminal region lacks structure. Here we found that an 18 amino acid
      peptide, S18, which corresponded to residues G22-A39 of the SPLUNC1 NH2 terminus
      inhibited ENaC activity to a similar degree as full-length SPLUNC1 (~2.5 fold),
      while SPLUNC1 protein lacking this region was without effect. S18 did not inhibit
      the structurally related acid-sensing ion channels, indicating specificity for
      ENaC. However, S18 preferentially bound to the betaENaC subunit in a
      glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic
      fibrosis (CF) lung disease. Unlike control, CF human bronchial epithelial
      cultures (HBECs) where airway surface liquid (ASL) height was abnormally low (4.2
      +/- 0.6 MUm), addition of S18 prevented ENaC-led ASL hyperabsorption and
      maintained CF ASL height at 7.9 +/- 0.6 MUm, even in the presence of neutrophil
      elastase, which is comparable to heights seen in normal HBECs. Our data also
      indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the
      main molecule by neutrophil elastase, suggesting that it may still be active
      during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC
      by the S18 peptide suggests that this peptide may be suitable for treating CF
      lung disease. 

PMID- 24124191
TI  - Local cAMP signaling in disease at a glance.
AB  - The second messenger cyclic AMP (cAMP) operates in discrete subcellular regions
      within which proteins that synthesize, break down or respond to the second
      messenger are precisely organized. A burgeoning knowledge of compartmentalized
      cAMP signaling is revealing how the local control of signaling enzyme activity
      impacts upon disease. The aim of this Cell Science at a Glance article and the
      accompanying poster is to highlight how misregulation of local cyclic AMP
      signaling can have pathophysiological consequences. We first introduce the core
      molecular machinery for cAMP signaling, which includes the cAMP-dependent protein
      kinase (PKA), and then consider the role of A-kinase anchoring proteins (AKAPs)
      in coordinating different cAMP-responsive proteins. The latter sections
      illustrate the emerging role of local cAMP signaling in four disease areas:
      cataracts, cancer, diabetes and cardiovascular diseases. 

PMID- 24124193
TI  - Methods for assessing and representing mammographic density: an analysis of 4
      case-control studies.
AB  - To maximize statistical power in studies of mammographic density and breast
      cancer, it is advantageous to combine data from several studies, but
      standardization of the density assessment is desirable. Using data from 4 case
      control studies, we describe the process of reassessment and the resulting
      correlation between values, identify predictors of differences in density
      readings, and evaluate the strength of the association between mammographic
      density and breast cancer risk using different representations of density values.
      The pooled analysis included 1,699 cases and 2,422 controls from California (1990
      1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010,
      a single reader reassessed all images for mammographic density using Cumulus
      software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean
      difference between original and reassessed percent density values was -0.7% (95%
      confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by
      location (r = 0.80-0.89). Case status, weight status, age, parity, density
      assessment method, mammogram view, and race/ethnicity were significant
      determinants of the difference between original and reassessed values; in
      combination, these factors explained 9.2% of the variation. The associations of
      mammographic density with breast cancer and the model fits were similar using the
      original values and the reassessed values but were slightly strengthened when a
      calibrated value based on 100 reassessed radiographs was used.

PMID- 24124194
TI  - Evidence for sexually dimorphic associations between maternal characteristics and
      anogenital distance, a marker of reproductive development.
AB  - Data from animal models, historical cohorts, and modern epidemiologic studies
      have suggested that maternal characteristics can affect reproductive health of
      offspring; however, distinguishing between prenatal and postnatal contributions
      is difficult. Anogenital distance (AGD), the distance from the anus to the
      genitals, is believed to be a biomarker of prenatal androgen exposure in many
      species, and in humans it has been associated with several adult reproductive
      health outcomes. We used data from a pregnancy cohort study conducted in 4 US
      cities from 1999-2005 to examine whether AGD measurements in infants were
      associated with maternal self-reported age at conception, age at menarche, age at
      first birth, parity, and gravidity. AGD was measured in 289 infants (140 male,
      149 female) born to study participants. After adjustment for relevant covariates,
      in linear regression models stratified by infant sex, maternal age was positively
      associated with AGD in male infants (AGD, anus to penis: beta = 0.50, P = 0.002;
      AGD, anus to scrotum: beta = 0.29, P = 0.02) but not female infants. Parity was
      inversely associated with AGD (anus to scrotum; beta = -1.68, P = 0.03) in male
      infants. No other maternal characteristic predicted AGD in either sex. The
      mechanism underlying the unexpected relationship between maternal characteristics
      and AGD is unknown; however, we suggest several possibilities for future study.

PMID- 24124195
TI  - Maternal vitamin D status and spontaneous preterm birth by placental histology in
      the US Collaborative Perinatal Project.
AB  - The objective of this study was to determine the association between maternal 25
      hydroxyvitamin D (25(OH)D) and the risk of spontaneous preterm birth (sPTB)
      before 35 weeks' gestation. A random subcohort from the US Collaborative
      Perinatal Project (1959-1965) was sampled (n = 2,629) and augmented with all
      remaining cases of sPTB before 35 weeks' gestation for a total of 767 cases.
      Banked serum samples collected at 26 weeks' gestation or earlier were assayed for
      25(OH)D. Constructs for vascular histology and inflammatory histology were
      developed from placental pathology examinations. There was no relationship
      between 25(OH)D and sPTB among white women. Among nonwhite mothers, serum 25(OH)D
      levels of 30-<50, 50-<75, and >=75 nmol/L were associated with reductions of 1.0
      1.6 cases of sPTB per 100 live births and 20%-30% reductions in risk of sPTB
      compared with 25(OH)D levels less than 30 nmol/L after adjustment for
      prepregnancy body mass index (weight (kg)/height (m)(2)), season, and other
      confounders. This association was driven by inflammation-mediated cases of sPTB
      and sPTB cases without placental lesions. A sensitivity analysis for unmeasured
      confounding by exercise, fish intake, and skin color suggested some bias away
      from the null in the conventional results, but conclusions were generally
      supported. The vitamin D-sPTB relationship should be examined in modern cohorts
      with detailed data on skin pigmentation and other covariates.

PMID- 24124196
TI  - Decreased risk of celiac disease in patients with Helicobacter pylori
      colonization.
AB  - The prevalence of celiac disease (CD) has increased in recent decades without a
      clear explanation. The "hygiene hypothesis" theorizes that decreased exposure to
      bacterial antigens may trigger autoimmunity. We aimed to determine whether
      Helicobacter pylori infection and CD were associated among patients undergoing
      upper gastrointestinal endoscopy. We performed a cross-sectional study of
      patients who underwent esophagogastroduodenoscopy with submission of gastric and
      duodenal biopsies to Miraca Life Sciences, Inc. (Irving, Texas), a US commercial
      pathology laboratory, during a 4.5-year period (January 2008-June 2012). We
      compared the prevalence of H. pylori in CD patients with that in persons without
      CD. We performed multiple logistic regression analysis, adjusting odds ratios for
      patient age, gender, and racial, ethnic, and socioeconomic factors. Among 136,179
      patients, a total of 2,689 (2.0%) had CD. H. pylori prevalence was significantly
      lower in patients with CD (4.4%) than in those without CD (8.8%; P < 0.0001).
      After adjustment for the above covariates, this inverse relationship remained
      strong (adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.40,
      0.58). The relationships were similar in men (unadjusted OR = 0.51, 95% CI: 0.38,
      0.69) and women (unadjusted OR = 0.46, 95% CI: 0.36, 0.58) and in all age groups.
      We conclude that H. pylori presence and CD are inversely associated, a
      relationship that persists after adjustment for socioeconomic factors. Future
      studies should address whether H. pylori modulates immune responses to ingested
      gluten. 

PMID- 24124197
TI  - Youth in transition: life skills among perinatally HIV-infected and HIV-exposed
      adolescents.
AB  - OBJECTIVE: To examine mastery of life skills necessary for independent adulthood
      among perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected
      (PHIV-) youth. METHODS: Participants were recruited from four medical centers in
      New York City as part of a longitudinal study. Data for this article came from
      interviews of 150 PHIV+ and 95 PHIV- youth (age 13-24 years) and their
      caregivers. Life skills mastery was assessed using the Ansell-Casey Life Skills
      Assessment (ACLSA). RESULTS: PHIV+ youth had lower daily living skill mastery
      than PHIV- youth according to both youth and caregivers, and lower self-care
      mastery according to caregiver report. No HIV-status group differences were found
      in social relationships scores, but PHIV- youth had higher scores than an ACLSA
      benchmark sample. CONCLUSIONS: PHIV+ youth may need supportive services in daily
      living and self-care needs to transition into adulthood. Normal-to-high
      functioning in social relationships may be important for learning to live
      independently.

PMID- 24124199
TI  - A novel radiographic index for the diagnosis of posterior acromioclavicular joint
      dislocations.
AB  - BACKGROUND: Posterior acromioclavicular (AC) joint dislocations are frequently
      misclassified because posterior translation of the clavicle is difficult to
      evaluate in Zanca radiograph views. A novel radiographic index was used in this
      study to accurately diagnose posterior dislocations of the AC joint. HYPOTHESIS:
      This novel index has a high degree of accuracy for the diagnosis of posterior AC
      joint dislocations. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: This was an analytic, descriptive study of 150 patients with different
      grades of AC injuries according to the Rockwood classification (30 patients for
      each grade of injury: I, II, III, IV, and V). The diagnosis of an AC injury was
      made both clinically and radiographically by using comparative Zanca and axillary
      views. Two measurements were performed in Zanca views: the coracoclavicular
      distance and the AC width distance. A width index was calculated for each
      patient. The Student t test, Bonferroni test, logistic regression, linear
      regression, and receiver operating characteristic (ROC) curves were used for
      statistical analysis. Forty cases were impartially selected to obtain a kappa
      concordance value. RESULTS: The average value of the AC width index per group
      (according to the Rockwood classification) was as follows: type I, 2.1% (range, 
      12% to 25%); type II, 4.2% (range, -19% to 29%); type III, 19.1% (range, -59% to
      91%); type IV, 110.3% (range, 47% to 181%); and type V, -3.8% (range, -71% to
      62%). There was a significant difference between the average width index in the
      patients with type IV injuries and those in the remaining groups (P < .05). The
      ROC curve showed that a width index of 60% has a sensitivity of 95.7% and
      specificity of 97.5%, with a positive predictive value of 96.7% and negative
      predictive value of 95.6% to predict a type IV injury. Intraobserver reliability
      was rated as substantial agreement for each of 3 observers; the interobserver
      reliability of the 3 independent raters was almost perfect. CONCLUSION: An AC
      width index of >=60% is highly accurate for the diagnosis of a posterior AC joint
      dislocation, with high intraobserver and interobserver concordance.

PMID- 24124198
TI  - Preferential loading of the ACL compared with the MCL during landing: a novel in
      sim approach yields the multiplanar mechanism of dynamic valgus during ACL
      injuries.
AB  - BACKGROUND: Strong biomechanical and epidemiological evidence associates knee
      valgus collapse with isolated, noncontact anterior cruciate ligament (ACL)
      injuries. However, a concomitant injury to the medial collateral ligament (MCL)
      would be expected under valgus collapse, based on the MCL's anatomic orientation
      and biomechanical role in knee stability. Purpose/ HYPOTHESIS: The purpose of
      this study was to investigate the relative ACL to MCL strain patterns during
      physiological simulations of a wide range of high-risk dynamic landing scenarios.
      We hypothesized that both knee abduction and internal tibial rotation moments
      would generate a disproportionate increase in the ACL strain relative to the MCL
      strain. However, the physiological range of knee abduction and internal tibial
      rotation moments that produce ACL injuries are not of sufficient magnitude to
      compromise the MCL's integrity consistently. STUDY DESIGN: Controlled laboratory
      study. METHODS: A novel in sim approach was used to test our hypothesis.
      Seventeen cadaveric lower extremities (mean age, 45 +/- 7 years; 9 female and 8
      male) were tested to simulate a broad range of landings after a jump under
      anterior tibial shear force, knee abduction, and internal tibial rotation at 25
      degrees  of knee flexion. The ACL and MCL strains were quantified using
      differential variable reluctance transducers. An extensively validated, detailed
      finite element model of the lower extremity was used to help better interpret
      experimental findings. RESULTS: Anterior cruciate ligament failure occurred in 15
      of 17 specimens (88%). Increased anterior tibial shear force and knee abduction
      and internal tibial rotation moments resulted in significantly higher ACL:MCL
      strain ratios (P < .05). Under all modes of single-planar and multiplanar
      loading, the ACL:MCL strain ratio remained greater than 1.7, while the relative
      ACL strain was significantly higher than the relative MCL strain (P < .01).
      Relative change in the ACL strain was demonstrated to be significantly greater
      under combined multiplanar loading compared with anterior tibial shear force (P =
      .016), knee abduction (P = .018), and internal tibial rotation (P < .0005)
      moments alone. CONCLUSION: While both the ACL and the MCL resist knee valgus
      during landing, physiological magnitudes of the applied loads leading to high ACL
      strain levels and injuries were not sufficient to compromise the MCL's integrity.
      CLINICAL RELEVANCE: A better understanding of injury mechanisms may provide
      insight that improves current risk screening and injury prevention strategies.
      Current findings support multiplanar knee valgus collapse as a primary factor
      contributing to a noncontact ACL injury.

PMID- 24124200
TI  - Trends in asbestos and non-asbestos fibre concentrations in the lung tissues of
      Japanese patients with mesothelioma.
AB  - OBJECTIVES: We aimed to elucidate changes in asbestos and non-asbestos fibre
      concentrations in the lung tissues of Japanese patients with mesothelioma over
      time. METHODS: Lung tissues were obtained from 46 patients with mesothelioma who
      died or underwent surgery between 1971 and 2005. All of the patients had a
      history of occupational asbestos exposure. We classified patients into four
      groups according to the period during which their lung tissue was obtained.
      Asbestos and non-asbestos fibre concentrations were determined by transmission
      electron microscopy with energy-dispersive X-ray analysis using a low-temperature
      ashing procedure. RESULTS: From the 1970s to the 2000s, we observed a decrease in
      the geometric mean of total asbestos concentration (67.4-1.05 million fibres per
      gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry
      lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry
      lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry
      lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years,
      and the mean duration since the last exposure increased from 0.3 to 21.5 years.
      The percentage of longer fibres to total fibres tended to increase over time,
      whereas the mean fibre length did not differ significantly. CONCLUSIONS: The
      present study suggested that asbestos and non-asbestos fibre concentrations in
      the lung tissues of Japanese patients with mesothelioma who have occupational
      histories of asbestos exposure may have decreased from the 1970s to the 2000s.

PMID- 24124201
TI  - Adequacy and accessibility.

PMID- 24124202
TI  - Communication modality sampling for a toddler with Angelman syndrome.
AB  - PURPOSE: Vocal, gestural, and graphic communication modes were implemented
      concurrently with a toddler with Angelman syndrome to identify the most
      efficiently learned communication mode to emphasize in an initial augmentative
      communication system. METHOD: Symbols representing preferred objects were
      introduced in vocal, gestural, and graphic communication modes using an
      alternating treatment single-subject experimental design. Conventionally accepted
      prompting strategies were used to teach symbols in each communication mode.
      Because the learner did not vocally imitate, vocal mode intervention focused on
      increasing vocal frequency as an initial step. RESULTS: When graphic and gestural
      mode performances were compared, the learner most accurately produced requests in
      graphic mode (percentage of nonoverlapping data = 96). Given the lack of success
      in prompting vocal productions, a comparison between vocal and the other two
      communication modes was not made. CONCLUSION: A growing body of evidence suggests
      that concurrent modality sampling is a promising low-inference, data-driven
      procedure that can be used to inform selection of a communication mode(s) for
      initial emphasis with young children. Concurrent modality sampling can guide
      clinical decisions regarding the allocation of treatment resources to promote
      success in building an initial communicative repertoire.

PMID- 24124203
TI  - A moratorium on breeding better babies.

PMID- 24124204
TI  - Lead resistance in micro-organisms.
AB  - Lead (Pb) is an element present in the environment that negatively affects all
      living organisms. To diminish its high toxicity, micro-organisms have developed
      several mechanisms that allow them to survive exposure to Pb(II). The main
      mechanisms of lead resistance involve adsorption by extracellular
      polysaccharides, cell exclusion, sequestration as insoluble phosphates, and ion
      efflux to the cell exterior. This review describes the various lead resistance
      mechanisms, and the regulation of their expression by lead binding regulatory
      proteins. Special attention is given to the Pbr system from Cupriavidus
      metallidurans CH34, which involves a unique mechanism combining efflux and lead
      precipitation. 

PMID- 24124205
TI  - Hedgehog signaling requires motile cilia in the sea urchin.
AB  - A relatively small number of signaling pathways govern the early patterning
      processes of metazoan development. The architectural changes over time to these
      signaling pathways offer unique insights into their evolution. In the case of
      Hedgehog (Hh) signaling, two very divergent mechanisms of pathway transduction
      have evolved. In vertebrates, signaling relies on trafficking of Hh pathway
      components to nonmotile specialized primary cilia. In contrast, protostomes do
      not use cilia of any kind for Hh signal transduction. How these divergent
      lineages adapted such dramatically different ways of activating the signaling
      pathway is an unanswered question. Here, we present evidence that in the sea
      urchin, a basal deuterostome, motile cilia are required for embryonic Hh signal
      transduction, and the Hh receptor Smoothened (Smo) localizes to cilia during
      active Hh signaling. This is the first evidence that Hh signaling requires motile
      cilia and the first case of an organism requiring cilia outside of the vertebrate
      lineage. 

PMID- 24124206
TI  - The effective population sizes of the anthropoid ancestors of the human
      chimpanzee lineage provide insights on the historical biogeography of the great
      apes.
AB  - The recent development of methods that apply coalescent theory to phylogenetic
      problems has enabled the study of the population-level phenomena that drove the
      diversification of anthropoid primates. Effective population size, Ne, is one of
      the main parameters that constitute the theoretical underpinning of these new
      analytical approaches. For this reason, the ancestral N(e) of selected primate
      lineages has been thoroughly investigated. However, for some of these lineages,
      the estimates of ancestral N(e) reported in several studies present significant
      variation. This is the case for the common ancestor of humans and chimpanzees.
      Moreover, several ancestral anthropoid lineages have been ignored in the studies
      conducted so far. Because N(e) is fundamental to understand historic species
      demography, it is a crucial component of a complete description of the historical
      scenario of primate evolution. It also provides information that is helpful for
      differentiating between competing biogeographical hypotheses. In this study, the
      effective population sizes of the anthropoid ancestors of the human-chimp lineage
      are inferred using data sets of coding and noncoding sequences. A general pattern
      of a serial decline of population sizes is found between the ancestral lineage of
      Anthropoidea and that of Homo and Pan. When the theoretical distribution of gene
      trees was derived from the parametric estimates obtained, it closely corresponded
      to the empirical frequency of inferred gene trees along the genome. The most
      abrupt decrease of N(e) was found between the ancestors of all great apes and
      those of the African great apes alone. This suggests the occurrence of a genetic
      bottleneck during the evolution of Homininae, which corroborates the origin of
      African apes from a Eurasian ancestor.

PMID- 24124207
TI  - The pattern and evolution of looped gene bendability.
AB  - Gene looping, defined as the physical interaction between the promoter and
      terminator regions of a RNA polymerase II-transcribed gene, is widespread in
      yeast and mammalian cells. Gene looping has been shown to play important roles in
      transcription. Gene-loop formation is dependent on regulatory proteins localized
      at the 5' and 3' ends of genes, such as TFIIB. However, whether other factors
      contribute to gene looping remains to be elucidated. Here, we investigated the
      contribution of intrinsic DNA and chromatin structures to gene looping. We found
      that Saccharomyces cerevisiae looped genes show high DNA bendability around
      middle and 3/4 regions in open reading frames (ORFs). This bendability pattern is
      conserved between yeast species, whereas the position of bendability peak varies
      substantially among species. Looped genes in human cells also show high DNA
      bendability. Nucleosome positioning around looped ORF middle regions is unstable.
      We also present evidence indicating that this unstable nucleosome positioning is
      involved in gene looping. These results suggest a mechanism by which DNA
      bendability and unstable nucleosome positioning could assist in the formation of
      gene loops. 

PMID- 24124216
TI  - Q&A: Geoffrey Shapiro on phase I drug trials. Spoke with Suzanne Rose.

PMID- 24124208
TI  - Contribution of selection for protein folding stability in shaping the patterns
      of polymorphisms in coding regions.
AB  - The patterns of polymorphisms in genomes are imprints of the evolutionary forces
      at play in nature. In particular, polymorphisms have been extensively used to
      infer the fitness effects of mutations and their dynamics of fixation. However,
      the role and contribution of molecular biophysics to these observations remain
      unclear. Here, we couple robust findings from protein biophysics, enzymatic flux
      theory, the selection against the cytotoxic effects of protein misfolding, and
      explicit population dynamics simulations in the polyclonal regime. First, we
      recapitulate results on the dynamics of clonal interference and on the shape of
      the DFE, thus providing them with a molecular and mechanistic foundation. Second,
      we predict that if evolution is indeed under the dynamic equilibrium of mutation
      selection balance, the fraction of stabilizing and destabilizing mutations is
      almost equal among single-nucleotide polymorphisms segregating at high allele
      frequencies. This prediction is proven true for polymorphisms in the human coding
      region. Overall, our results show how selection for protein folding stability
      predominantly shapes the patterns of polymorphisms in coding regions. 

PMID- 24124217
TI  - Catch-22 for cancer tests.

PMID- 24124228
TI  - Are short telomeres predictive of advanced cancer?
AB  - The combination of variable telomere length in cancer cells and shorter telomere
      length in cancer-associated stromal cells strongly correlates with progression to
      prostate cancer metastasis and cancer death. The implication is that telomere
      length measurements have potential not only as prognostic indicators of prostate
      cancer outcomes but also as risk stratification enrichment biomarkers for
      individualized therapeutic interventions.

PMID- 24124229
TI  - New connections between old pathways: PDK1 signaling promotes cellular
      transformation through PLK1-dependent MYC stabilization.
AB  - Limited understanding of the functional link between multiple oncogenic pathways
      is a major barrier in the ongoing effort of cancer biologists to design an
      effective therapeutic approach to treat malignancies characterized by driver
      oncogenic network signals. In this issue of Cancer Discovery, Tan and colleagues
      elucidate a novel PDK1-PLK1-MYC signaling pathway connecting two fundamental
      oncogenic programs, phosphoinositide 3-kinase and MYC. They define the functional
      role for PDK1-PLK1-MYC signaling in cancer cell survival and tumor formation and
      show the therapeutic benefit of inhibiting PDK1 and PLK1 pharmacologically in
      cancer, tackling the most undruggable tumors defined by elevated levels of the
      MYC oncoprotein.

PMID- 24124230
TI  - Hypoxia signaling--license to metastasize.
AB  - Hypoxia-inducible factors (HIF) have long been linked to malignant tumor
      phenotypes in various cancer types, and several downstream mediators of HIF
      action are deregulated in metastatic carcinomas. A new study links hypoxia
      induced collagen remodeling to sarcoma progression, providing evidence for
      unifying mechanisms of carcinoma and sarcoma metastasis.

PMID- 24124231
TI  - Glycolysis back in the limelight: systemic targeting of HK2 blocks tumor growth.
AB  - In a recent issue of Cancer Cell, Patra and colleagues report findings that
      underscore the importance of Hexokinase 2 (HK2) in tumor initiation and
      maintenance. The authors also show that HK2 can be systemically deleted without
      adverse physiologic consequences. These findings provide attractive insights into
      HK2 deletion as a potential therapeutic intervention for cancer.

PMID- 24124264
TI  - An experimental and modeling study of the low- and high-temperature oxidation of
      cyclohexane.
AB  - The experimental study of the oxidation of cyclohexane has been performed in a
      jet-stirred reactor at temperatures ranging from 500 to 1100 K (low- and
      intermediate temperature zones including the negative temperature-coefficient
      area), at a residence time of 2 s and for dilute mixtures with equivalence ratios
      of 0.5, 1, and 2. Experiments were carried out at quasi-atmospheric pressure
      (1.07 bar). The fuel and reaction product mole fractions were measured using
      online gas chromatography. A total of 34 reaction products have been detected and
      quantified in this study. Typical reaction products formed in the low-temperature
      oxidation of cyclohexane include cyclic ethers (1,2-epoxycyclohexane and 1,4
      epoxycyclohexane), 5-hexenal (formed from the rapid decomposition of 1,3
      epoxycyclohexane), cyclohexanone, and cyclohexene, as well as benzene and phenol.
      Cyclohexane displays high low-temperature reactivity with well-marked negative
      temperature-coefficient (NTC) behavior at equivalence ratios 0.5 and 1. The fuel
      rich system (phi = 2) is much less reactive in the same region and exhibits no
      NTC. To the best of our knowledge, this is the first jet-stirred reactor study to
      report NTC in cyclohexane oxidation. Laminar burning velocities were also
      measured by the heated burner method at initial gas temperatures of 298, 358, and
      398 K and at 1 atm. The laminar burning velocity values peak at phi = 1.1 and are
      measured as 40 and 63.1 cm/s for Ti = 298 and 398 K, respectively. An updated
      detailed chemical kinetic model including low-temperature pathways was used to
      simulate the present (jet-stirred reactor and laminar burning velocity) and
      literature experimental (laminar burning velocity, rapid compression machine, and
      shock tube ignition delay times) data. Reasonable agreement is observed with most
      of the products observed in our reactor, as well as the literature experimental
      data considered in this paper.

PMID- 24124232
TI  - Connecting genomic alterations to cancer biology with proteomics: the NCI
      Clinical Proteomic Tumor Analysis Consortium.
AB  - The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium
      is applying the latest generation of proteomic technologies to genomically
      annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative
      of the NCI and the National Human Genome Research Institute. By providing a fully
      integrated accounting of DNA, RNA, and protein abnormalities in individual
      tumors, these datasets will illuminate the complex relationship between genomic
      abnormalities and cancer phenotypes, thus producing biologic insights as well as
      a wave of novel candidate biomarkers and therapeutic targets amenable to
      verification using targeted mass spectrometry methods.

PMID- 24124265
TI  - A Logarithmic Complexity Floating Frame of Reference Formulation with
      Interpolating Splines for Articulated Multi-Flexible-Body Dynamics.
AB  - An interpolating spline-based approach is presented for modeling multi-flexible
      body systems in the divide-and-conquer (DCA) scheme. This algorithm uses the
      floating frame of reference formulation and piecewise spline functions to
      construct and solve the non-linear equations of motion of the multi-flexible-body
      system undergoing large rotations and translations. The new approach is compared
      with the flexible DCA (FDCA) that uses the assumed modes method [1]. The FDCA, in
      many cases, must resort to sub-structuring to accurately model the deformation of
      the system. We demonstrate, through numerical examples, that the interpolating
      spline-based approach is comparable in accuracy and superior in efficiency to the
      FDCA. The present approach is appropriate for modeling flexible mechanisms with
      thin 1D bodies undergoing large rotations and translations, including those with
      irregular shapes. As such, the present approach extends the current capability of
      the DCA to model deformable systems. The algorithm retains the theoretical
      logarithmic complexity inherent in the DCA when implemented in parallel.

PMID- 24124266
TI  - An assessment of external biosecurity on Southern Ontario swine farms and its
      application to surveillance on a geographic level.
AB  - Risk-based surveillance is becoming increasingly important in the veterinary and
      public health fields. It serves as a means of increasing surveillance sensitivity
      and improving cost-effectiveness in an increasingly resource-limited environment.
      Our approach for developing a tool for the risk-based geographical surveillance
      of contagious diseases of swine incorporates information about animal density and
      external biosecurity practices within swine herds in southern Ontario. The
      objectives of this study were to group the sample of herds into discrete
      biosecurity groups, to develop a map of southern Ontario that can be used as a
      tool in the risk-based geographical surveillance of contagious swine diseases,
      and to identify significant predictors of biosecurity group membership. A subset
      of external biosecurity variables was selected for 2-step cluster analysis and
      latent class analysis (LCA). It was determined that 4 was the best number of
      groups to describe the data, using both analytical approaches. The authors named
      these groups: i) high biosecurity herds that were open with respect to
      replacement animals; ii) high biosecurity herds that were closed with respect to
      replacement animals; iii) moderate biosecurity herds; and iv) low biosecurity
      herds. The risk map was developed using information about the geographic
      distribution of herds in the biosecurity groups, as well as the density of swine
      sites and of grower-finisher pigs in the study region. Finally, multinomial
      logistic regression identified heat production units (HPUs), number of incoming
      pig shipments per month, and herd type as significant predictors of biosecurity
      group membership. It was concluded that the ability to identify areas of high and
      low risk for disease may improve the success of surveillance and eradication
      projects. 

PMID- 24124267
TI  - A retrospective study on the etiological diagnoses of diarrhea in neonatal
      piglets in Ontario, Canada, between 2001 and 2010.
AB  - Laboratory surveillance data from the Animal Health Laboratory, University of
      Guelph, on the etiological diagnoses of neonatal diarrhea in piglets were
      analyzed to determine the relative importance and trends of different enteric
      pathogens in Ontario. A total of 237 cases, including live and dead 1- to 7-day
      old piglets, were submitted for diagnosis of gastrointestinal illness between
      2001 and 2010. The combined frequencies for cases of gastrointestinal illness
      involving Escherichia coli, Clostridium perfringens type A, rotavirus, and
      Clostridium difficile, either as single pathogens or a complex of pathogens,
      accounted for 56% of the total cases. In a total of 33% of cases of
      gastrointestinal illness, an etiological agent was not identified. The frequency
      of cases diagnosed with enterotoxigenic E. coli was decreased from 2007. Cases
      submitted in 2010 were more likely to be diagnosed with C. perfringens type A
      compared to cases submitted in 2002 to 2007 (P < 0.05). There was a significant
      trend for cases submitted in the winter to be diagnosed with C. perfringens type
      A, enterotoxigenic E. coli, rotavirus, and Cystoisospora suis (formerly Isospora
      suis) (P < 0.05). Enterotoxigenic E. coli was less likely diagnosed if C.
      difficile, C. perfringens, or rotavirus were detected (P < 0.05). Younger piglets
      were more likely to be diagnosed with C. perfringens type A (P < 0.05) and C.
      difficile (P < 0.05) than older piglets. This study shows that E. coli, C.
      perfringens type A, rotavirus, and C. difficile are enteric pathogens of concern
      for Ontario swine farrowing operations and further research is required to
      understand the reasons for the cases that are not diagnosed. 

PMID- 24124268
TI  - Species-specificity of equine and porcine Lawsonia intracellularis isolates in
      laboratory animals.
AB  - Lawsonia intracellularis infection causes proliferative enteropathy (PE) in many
      mammalian species, with porcine and equine proliferative enteropathy (PPE and
      EPE) known worldwide. Hamsters are a well-published animal model for PPE
      infection studies in pigs. There is no laboratory animal model for EPE infection
      studies and it is not known whether there is species-specificity for equine or
      porcine isolates of L. intracellularis in animal models. The objective of this
      study was to determine whether it is possible to generate typical EPE lesions in
      hamsters after inoculation with an equine strain of L. intracellularis (EPE
      strain) and whether it is comparatively possible to generate PPE lesions in
      rabbits after inoculation with a porcine strain of L. intracellularis (PPE
      strain). In 2 separate trials, 4-week-old and 3-week-old weanling golden Syrian
      hamsters were challenged with EPE strains and compared to uninfected (both
      trials) and PPE-infected controls (Trial 2 only). Concurrently, 6 female New
      Zealand white juvenile rabbits were infected with PPE strain and observed
      concomitantly to 8 similar rabbits infected with EPE strain for a different
      experiment. Hamsters and rabbits were observed for 21 to 24 days post-infection
      (DPI), depending on the experiment. Neither infected species developed clinical
      signs. The presence of disease was assessed with diagnostic techniques
      classically used for pigs and horses: immune-peroxidase monolayer assay on sera;
      quantitative polymerase chain reaction (qPCR) detection of molecular DNA in
      feces; and hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) on
      intestinal tissues. Our results showed that EPE-challenged hamsters do not
      develop infection when compared with PPE controls (IHC, P = 0.009; qPCR, P =
      0.0003). Conversely, PPE-challenged rabbits do not develop typical intestinal
      lesions in comparison to EPE-challenged rabbits, with serological response at 14
      DPI being significantly lower (P = 0.0023). In conclusion, PPE and EPE strains
      appear to have different host-specificities for hamsters and rabbits,
      respectively. 

PMID- 24124269
TI  - Analgesic and motor effects of a high-volume intercoccygeal epidural injection of
      0.125% or 0.0625% bupivacaine in adult cows.
AB  - The objectives of this study were to determine the analgesic and motor effects of
      a high-volume intercoccygeal epidural injection of bupivacaine at 2
      concentrations in cows. A prospective, randomized, blinded, crossover trial was
      conducted on 6 adult cows. An indwelling epidural catheter was placed in the
      first intercoccygeal space and advanced 10 cm cranially. All the cows received 3
      treatments with a washout period of 48 h: saline (control), 0.125% bupivacaine
      (high dose), or 0.0625% bupivacaine (low dose), at a final volume of 0.15 mL per
      kilogram of body weight, infused manually into the epidural space over a period
      of 15 min. The anal and tail tone and motor deficits of the pelvic limbs were
      evaluated in 5 of the cows with use of a numerical rating scale and a visual
      analogue scale (VAS). Sensory block was assessed in 4 of the cows by the response
      to needle pricks in different regions with the use of a VAS. Measurements were
      obtained before and at different time points after injection, up to 360 min.
      Analysis of variance for repeated measures and post-hoc Tukey's and Dunnett's
      tests were used. Differences were considered significant when the P-value was <=
      0.05. One cow became recumbent 6 h after injection. Anal and tail tones were
      significantly decreased and motor deficits of the pelvic limbs were significantly
      increased after bupivacaine treatment compared with control treatment. The
      overall mean VASpain scores +/- standard deviation were 66 +/- 8 after control
      treatment, 52 +/- 5 after low-dose bupivacaine treatment, and 43 +/- 5 after high
      dose bupivacaine treatment. The pain scores were significantly lower in caudal
      regions up to the saphenous nerve after high-dose bupivacaine treatment compared
      with control treatment and significantly lower in the anus, vulva, and tail after
      low-dose bupivacaine treatment compared with control treatment. Thus, analgesia
      with moderate motor deficits of the pelvic limbs may be obtained with 0.125%
      bupivacaine administered epidurally. 

PMID- 24124270
TI  - The use of lung biopsy to determine early lung pathology and its association with
      health and production outcomes in feedlot steers.
AB  - The objectives of this study were to determine if percutaneous lung biopsy can be
      used to characterize early pathologic changes in bovine lung associated with
      bovine respiratory disease (BRD), to determine if specific infectious respiratory
      pathogens can be identified in association with these changes, and to determine
      whether pulmonary pathology at arrival and at the time of initial diagnosis are
      associated with health and production outcomes. One hundred auction-market
      derived crossbred steer calves from a commercial feedlot in southern Alberta were
      included in this study. A percutaneous lung biopsy technique was used to obtain
      lung samples from the right middle lung. Steers were sampled 295 times yielding
      283 samples with 210 (74%) containing lung tissue. Overall, histopathological
      changes were observed in 20 (9.5%) of lung biopsy samples. There were too few
      samples with pathology to reveal an association between lung pathology and
      subsequent health events. In general, percutaneous lung biopsy can be done safely
      on feedlot steers in a commercial feedlot setting with few clinical side effects.
      This technique did not prove useful as a diagnostic tool or prognostic indicator
      for early BRD. However, it may be useful for the diagnosis of BRD in targeted
      populations of commercial feedlot steers. 

PMID- 24124271
TI  - Reversible chemical restraint of free-range cattle with a concentrated
      combination of tiletamine-zolazepam, ketamine, and detomidine.
AB  - The aim of this study was to determine the efficacy of a concentrated combination
      of tiletamine-zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53
      mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free
      range cattle for clinical procedures. The combination was administered
      intramuscularly to 53 animals. Anesthesia was reversed with the alpha2
      adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with
      lidocaine when required. The TZKD combination induced suitable immobilization for
      minor surgical procedures or medical treatments. Anesthetic onset was rapid,
      taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of
      anesthesia depended on the time of administration of the antagonist; the animals
      recovered in the standing position in 12.9 +/- 8.9 min after the administration
      of atipamezole. The quality of anesthesia and analgesia were satisfactory. In
      conclusion, this TZKD combination can be used for both immobilization and minor
      surgical procedures in free-range cattle. 

PMID- 24124272
TI  - Effect of storage time and temperature on the total protein concentration and
      electrophoretic fractions in equine serum.
AB  - Serum protein electrophoresis (SPE) is a technique that could be considered one
      of the most useful diagnostic aids available to the clinician. The effect of
      storage time and temperature on the total proteins and electrophoretic fractions
      (albumin, alpha1-, alpha2-, beta1-, beta2-, and gamma-globulins) was assessed in
      24 healthy horses. All samples, collected by jugular vein puncture, were
      centrifuged and divided into 4 aliquots. The 1st aliquot was analyzed within 3 h
      from collection (time 0), the 2nd was refrigerated at +4 degrees C for 24 h, the
      3rd was refrigerated at +4 degrees C for 48 h, and the last was frozen at -20
      degrees C for 48 h. One-way repeated-measures analysis of variance (ANOVA) showed
      a significant effect (P < 0.05) of the different storage conditions on the
      concentrations of all the parameters studied and significant variations in the
      percentages of albumin, alpha1-globulins, alpha2-globulins, and gamma-globulins.
      Compared with time 0 the total protein concentration increased significantly
      after 48 h at -20 degrees C, the albumin percentage decreased after 48 h at -20
      degrees C, the alpha1-globulin percentage increased after 24 h at +4 degrees C,
      the alpha2-globulin percentage increased after 48 h at +4 degrees C and at -20
      degrees C, and the gamma-globulin percentage increased after 48 h at -20 degrees
      C. The results should help veterinary practitioners handle and store equine serum
      samples appropriately. Further investigations at different storage times and
      temperatures could be useful. 

PMID- 24124273
TI  - Evaluation of cerebrospinal fluid lactate and plasma lactate concentrations in
      anesthetized dogs with and without intracranial disease.
AB  - The objectives of this study were to establish a reference interval for canine
      cerebrospinal fluid lactate (CSFL) and to compare CSFL and plasma lactate (PL)
      concentrations in anesthetized dogs with and without intracranial disease. Using
      a prospective study, canine blood and cerebrospinal fluid were collected for
      lactate analysis in 11 dogs with intracranial disease after undergoing magnetic
      resonance imaging (MRI) (Group ID-MRI), in 10 healthy dogs post-MRI (Group H
      MRI), and in 39 healthy dogs after induction of anesthesia (Group H-Sx). Dogs
      were anesthetized for the procedures using different anesthetic protocols.
      Neurological scores (NS) and sedation scores (SS) were assessed pre-anesthesia in
      ID-MRI dogs. The CSFL reference interval [90% confidence interval (CI) for lower
      and upper limits] was 1.1 (1.0 to 1.2) to 2.0 (2.0 to 2.1) mmol/L. Mean +/- SD
      CSFL concentrations were: ID-MRI, 2.1 +/- 0.8; H-MRI, 1.6 +/- 0.4; and H-Sx, 1.6
      +/- 0.2 mmol/L. There was a tendency for higher CSFL in dogs in the ID-MRI group
      than in those in the H-MRI or H-Sx groups (P = 0.12). There was agreement between
      CSFL and PL in ID-MRI dogs (P = 0.007), but not in dogs in H-MRI (P = 0.5) or H
      Sx (P = 0.2). Of the ID-MRI dogs, those with worse NS had higher CSFL (r (2) =
      0.44). The correlation between CSFL and PL in dogs with intracranial disease and
      between worse NS and higher CSFL warrants further investigation into the use of
      CSFL and PL for diagnostic and prognostic purposes. 

PMID- 24124274
TI  - Sandwich-dot enzyme-linked immunosorbent assay for the detection of canine
      distemper virus.
AB  - A sandwich-dot enzyme-linked immunosorbent assay (dot ELISA) was developed for
      the detection of canine distemper virus (CDV). In 56 dogs suspected to have CD
      the rates of detection of CDV antigen in samples of blood lymphocytes and
      palpebral conjunctiva by dot ELISA and ELISA were, respectively, 91% (49/54) and
      81% (44/54) for the lymphocyte samples and 88% (28/32) and 75% (24/32) for the
      conjunctival samples. The CDV detection limits were 10 ng/50 MUL for dot ELISA
      and 40 ng/50 MUL for ELISA. The reliability of dot ELISA relative to electron
      microscopy was 96% with 22 samples: all 21 samples in which CDV particles were
      observed by electron microscopy yielded positive results with dot ELISA; the
      single sample in which particles were not observed yielded false-positive results
      with dot ELISA. The results indicate that the dot ELISA developed can serve as a
      reliable rapid diagnostic test in suspected cases of CD and also be useful for
      epidemiologic surveillance of the disease. 

PMID- 24124275
TI  - Needle-free delivery of an inactivated avian influenza H5N3 virus vaccine elicits
      potent antibody responses in chickens.
AB  - A needle-free delivery system was assessed as a route for providing quick, safe,
      and effective vaccination against avian influenza (AI). Two groups of chickens
      were vaccinated with a commercially available inactivated H5N3 virus vaccine
      delivered either with a needle-free device or with the conventional syringe-and
      needle method recommended by the vaccine manufacturer. The kinetic aspects of
      seroconversion, peak antibody levels, and antibody titers were measured by a
      combination of an indirect enzyme-linked immunosorbent assay and the
      hemagglutination-inhibition test and were all found to be similar in the 2 groups
      of chickens. We conclude that the needle-free delivery system could result in
      effective immunization against H5N1 AI epidemics and pandemics in chickens. 

PMID- 24124277
TI  - Pharmacognosy Magazine's new and improved Impact Factor - 1.525.

PMID- 24124276
TI  - The effects of dietary omega fatty acids on pregnancy rate, plasma prostaglandin
      metabolite levels, serum progesterone levels, and milk fatty-acid profile in beef
      cows.
AB  - The objectives were to determine the effects of feeding supplements rich in omega
      6 or omega-3 fatty acids (FA) during the late gestation to the early postpartum
      and breeding periods on reproduction and milk FA profile in beef cows. For each
      of two years, at the beginning of period 1 (mid-December), 72 beef cows, calving
      in January or February, were assigned to diets supplemented with roasted flaxseed
      (Flax) or roasted soybean (Soybean). For each of two years, after 11 wk (end of
      period 1), 18 cows of 36 in the Flax group were switched to the soybean
      supplement and 18 cows of 36 in the Soybean group were switched to the flax
      supplement (start of Period 2). Cows were bred by timed artificial insemination
      (TAI) in week 5 of period 2. The FA composition of the milk reflected the FA
      profile of the oilseed supplements. There were no differences in pregnancy rates
      among the 4 groups. The treatments had no effect on plasma prostaglandin
      metabolite levels or ratios at 4 to 11 d postpartum. At 5 to 6 d post- TAI,
      pregnant cows fed Flax in period 1 had lower (P < 0.05) plasma prostaglandin F
      metabolite (PGFM) levels and PGFM to prostaglandin E metabolite (PGEM) ratio than
      cows fed Soybean, but there were no significant differences at 19 to 20 d post
      TAI. Cows pregnant from TAI and fed Flax in period 2 had higher (P < 0.05) serum
      progesterone levels at 5 to 6 d post-TAI than cows fed Soybean, but there was no
      difference at 19 to 20 d post-TAI. The dietary treatments had no effect on
      pregnancy rates, but there were some effects on plasma PGFM levels, PGFM to PGEM
      ratios, and serum progesterone levels. The FA supplements influenced the FA
      composition of milk. 

PMID- 24124278
TI  - Ultra-performance liquid chromatography fingerprinting for quality control of
      Phragmitis rhizoma (Lugen) produced in Baiyangdian.
AB  - OBJECTIVE: To establish an ultra-performance liquid chromatography (UPLC)
      fingerprinting method for quality control of Phragmitis rhizoma from Baiyangdian.
      MATERIALS AND METHODS: Ultrasonic extraction with 70% methanol was performed on
      10 samples of P. rhizoma collected from 10 different villages in Baiyangdian. The
      sample solutions were analyzed by Waters UPLC equipped with the ACQUITY UPLC BEH
      C18 column and photodiode array (PDA) detector, and gradient eluted with
      acetonitrile/water as the mobile phase. The flow rate was set to 0.1 mL/min; the
      column temperature was set to 25 degrees C; and the detection wavelength was set
      to 285 nm. RESULTS: The chromatograms of the 10 samples showed 27 common peaks,
      of which one was identified as the ferulic acid standard. The similarity indexes
      were all above 0.82. Hierarchical cluster analysis showed that the constituents
      and their quantities differed according to the diameter of the original plant,
      which is related to its age. CONCLUSION: The UPLC fingerprinting method had the
      advantages of being fast, accurate, and highly efficient; this indicated that it
      can be used for quality control of P. rhizoma produced in Baiyangdian. Also, the
      relation between the quality and diameter/age of the plant needs to be further
      investigated.

PMID- 24124279
TI  - Influence of the mixture of Epimedii Herba and Ginkgo Folium extracts on the
      coronary flow of isolated hearts in rats.
AB  - BACKGROUND: In clinical practice, Epimedii Herba and Ginkgo Folium preparations
      are widely used in treatment of diseases such as coronary heart disease (angina)
      in China. However, there are no studies on the two-drug combination. OBJECTIVE:
      To explore the effect of the mixture of the Epimedii Herba extract (EE) and
      Ginkgo Folium extract (GE) on coronary flow of isolated hearts in rats. MATERIALS
      AND METHODS: EE and GE were prepared by reflux in alcohol, and processed with HPD
      100 macro-reticular resins; icariin from EE and total bilobalides from GE were
      determined by high performance liquid chromatography (HPLC). Fifty male Sprague
      Dawley (SD) mice were subdivided into five groups (10 rats each): Normal control
      group (NC), EE - 10 mg group, GE - 10 mg group, EE - 5 mg + GE - 5 mg group, and
      EE - 10 mg + GE - 10 mg group. Isolated hearts uniform pressure perfusion was
      proceeded with Langendorff system. RESULTS: The content of icariin in EE was
      20.8%. The total content including four kinds of bilobalides (ginkolide A-C and
      bilobalide) in GE was 8.6%. The coronary flow in the NC group remained stable
      before and after treatment, and the coronoray flow in the EE, GE, EE + GE groups
      was increased and the relative magnitude of heightening was 25.0-33.3%, and the
      coronary flow in EE + GE was significantly different from that in the single EE
      or GE group. CONCLUSION: EE or GE itself can heighten coronary flow of isolated
      hearts in rats. The activity of the mixture including EE and GE is better than
      that of single EE or GE, and the activity becomes larger when the dosage is
      doubled, and is related with dosage.

PMID- 24124280
TI  - Cytoprotective and antioxidant effects of phenolic compounds from Haberlea
      rhodopensis Friv. (Gesneriaceae).
AB  - BACKGROUND: Haberlea rhodopensis Friv. (Gesneriaceae) is a rare poikilohydric
      endemic and preglacial relict growing in Balkan Peninsula. Previous
      investigations demonstrated strong antioxidant, antimicrobial and antimutagenic
      potential of alcoholic extract from the plant. OBJECTIVE: The isolation of known
      caffeoyl phenylethanoid glucoside - myconoside and flavone-C-glycosides
      hispidulin 8-C-(2-O-syringoyl-beta-glucopyranoside), hispidulin 8-C-(6-O-acetyl-2
      O-syringoyl-beta-glucopyranoside), and hispidulin 8-C-(6-O-acetyl-beta
      glucopyranoside) from the leaves of H. rhodopensis was carried out. The aim of
      this study was to investigate cyto-protective and antioxidant effects of isolated
      compounds. MATERIALS AND METHODS: Antioxidant activity of isolated substances was
      examined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals; ferric
      reducing antioxidant power (FRAP) assay and inhibition of lipid peroxidation
      (LPO) in linoleic acid system by ferric thyocianate method. The compounds were
      investigated for their possible protective and antioxidant effects against tert
      butyl hydroperoxide-induced oxidative stress in isolated rat hepatocytes. The
      levels of thiobarbituric acid reactive substances were assayed as an index of
      LPO. Lactate dehydrogenase leakage, cell viability, and reduced glutathione
      depletion were used as signs of cytotoxicity. RESULTS: Myconoside demonstrated
      the highest DPPH radical scavenging, ABTS, FRAP, and antioxidant activity in
      linoleic acid system as well as the highest and statistically most significant
      protection and antioxidant activity against the toxic agent. CONCLUSION: Phenolic
      compounds isolated from H. rhodopensis demonstrated significant cytoprotective,
      radical scavenging potential, and inhibit lipid peroxidation, moreover,
      myconoside was found to be a new powerful natural antioxidant.

PMID- 24124281
TI  - Protective effects of onion-derived quercetin on glutamate-mediated hippocampal
      neuronal cell death.
AB  - BACKGROUND: Neurodegenerative diseases are characterized by progressive neuron
      degeneration in specific functional systems of the central or peripheral nervous
      system. This study investigated the protective effects of quercetin isolated from
      onion on neuronal cells and its protective mechanisms against glutamate-induced
      apoptosis in HT22 cells. MATERIALS AND METHODS: HT22 cells were cultured to study
      the neuroprotective mechanism of quercetin against glutamate-mediated oxidative
      stress. The intracellular reactive oxygen species (ROS) level and mitochondrial
      membrane potential (DeltaPsim) were measured. The protein expression of calpain,
      spectrin, Bcl-2, Bax, Bid, cytochrome c, and mitogen-activated protein kinases
      (MAPKs) was evaluated by Western blotting. RESULTS: Quercetin had a protective
      effect by reducing both intracellular ROS overproduction and glutamate-mediated
      Ca(2+) influx. These effects were due to the downregulation of several apoptosis
      related biochemical markers. Calpain expression was reduced and spectrin cleavage
      was inhibited by quercetin in glutamate-exposed HT22 cells. Disruption of the
      mitochondrial membrane potential (DeltaPsim), activation of the pro-apoptotic
      proteins Bid and Bax, and cytochrome c release in response to glutamate-induced
      oxidative stress were reduced. Quercetin also suppressed phosphorylation of
      MAPKs. CONCLUSION: This is the first report on the detailed mechanisms of the
      protective effect of quercetin on HT22 cells. Onion extract and quercetin may be
      useful for preventing or treating neurodegenerative disorders.

PMID- 24124282
TI  - Inhibition of wheat bran and it's active compoments on alpha-glucosidase in
      vitro.
AB  - BACKGROUND: Wheat bran is a traditional Chinese medicine; however, it is mostly
      used as feedstuff in China. Wheat bran is widely accepted as an important
      ingredient in many low-glycemic index foods in modern western societies; however,
      its glycemic control mechanism is unknown. OBJECTIVE: To determine potent alpha
      glucosidase inhibitory compounds from wheat bran and to identify the inhibition
      on alpha-glucosidase. MATERIALS AND METHODS: Ethanolic extract of wheat bran was
      prepared to evaluate the inhibitory activity on alpha-glucosidase, then
      fractionation of the extract was guided by in vitro enzyme-inhibition assay, and
      the potent alpha-glucosidase inhibitory compounds were identified by high
      performance liquid chromatography and atmospheric pressure chemical ionization
      mass spectrometry; finally the enzyme inhibition process was studied using the
      Michaelis-Menton and the Lineweaver-Burk equations. RESULTS: Both baker's yeast
      and rat intestinal enzymes were mostly inhibited (87.9% and 66.8% inhibition,
      respectively) at concentration 0.6 mg/mL of the ethanolic extract of wheat bran.
      The petroleum ether fraction in the ethanolic extract of wheat bran showed
      significant activity against rat intestinal alpha-glucosidase, and revealed a
      dose-dependent effect. The inhibition was 76.57% at 0.3 mg/mL and 100% at 0.6
      mg/mL. The active fraction 13 of petroleum ether fraction was identified as
      alkylresorcinols (ARs). ARs showed strong inhibition towards alpha-glucosidase
      and its IC50 value was found to be 37.58 MUg/mL. The enzyme kinetic studies
      showed that, in the presence of ARs, the Michaelis-Menton constant (K m) remains
      constant whereas the maximal velocity (V max) decreases, revealing a non
      competitive type of inhibition. CONCLUSION: The therapeutic potentiality of ARs
      in the management of the postprandial hyperglycemia will proliferate the
      utilization of wheat bran in controlling type 2 diabetes.

PMID- 24124283
TI  - Bioactivity studies on Musa seminifera Lour.
AB  - BACKGROUND: Musa seminifera Lour is a tree-like perennial herb that has been used
      in folk medicine in Bangladesh to heal a number of ailments. OBJECTIVE: To
      evaluate the antioxidant, analgesic, antidiarrheal, anthelmintic activities, and
      general toxicity of the ethanol extract of the roots. MATERIALS AND METHODS: The
      extract was assessed for free-radical-scavenging activity by the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay, total phenolic content (TPC) by the Folin Ciocalteu
      reagent, antioxidant activity by the ferric reducing power assay, analgesic
      activity by the acetic acid-induced writhing and hot-plate tests, antidiarrheal
      activity by the castor oil-induced diarrhea model in mice, anthelmintic activity
      on Paramphistomum cervi and Haemonchus contortus, and general toxicity by the
      brine shrimp lethality assay. RESULTS: The extract showed free-radical-scavenging
      activity with an IC50 value of 44.86 MUg/mL. TPC was 537.89 mg gallic acid
      equivalent/100 g of dried plant material. It showed concentration-dependent
      reducing power, and displayed 42.11 and 69.32% writhing inhibition at doses of
      250 and 500 mg/kg body weight, respectively. The extract also significantly
      raised the pain threshold at the above-mentioned dose levels. In vivo
      antidiarrheal property was substantiated by significant prolongation of latent
      period and decrease in total number of stools compared with the control. The LC50
      against brine shrimp nauplii was 36.21 MUg/mL. The extract exhibited dose
      dependent decrease in paralysis and death time of the helminths. CONCLUSION: The
      above results demonstrated that the plant possesses notable bioactivities and
      somewhat supports its use in folk medicine.

PMID- 24124284
TI  - Tissue culture of Sophora tonkinensis Gapnep. and its quality evaluation.
AB  - BACKGROUND: Sophora tonkinensis Gapnep. is an important rare medicinal plant in
      China. There were only a few papers on the rapid propagation of S. tonkinensis
      through in vitro tissue culture, and still no report focuses on the quality
      analysis of in vitro tissue culture plantlets. MATERIALS AND METHODS: The
      different concentrations of 6-benzylaminopurine (BAP), kinetin (KT), and indole-3
      acetic acid (IAA) were used to establish and screen the optimal rapid propagation
      technology of S. tonkinensis by orthogonal test; the different concentrations of
      a-naphthalene acetic acid (NAA), indole-3-butyric acid (IBA), and ABT rooting
      power (ABT) were used to screen the optimal rooting technology. For quality
      evaluation of tissue culture plants, three different sites were chose to finish
      planting experiment. The leaf characteristics, radix ex rhizoma yield, and
      contents of matrine and oxymatrine were evaluated, respectively, to provide
      evidence of high yield and good qualities of tissue culture plants. RESULTS: A
      large number of buds could be induced directly from epicotyl and hypocotyl
      explants on the Murashige and Skoog (MS) medium supplemented with 1.5 mg/l BAP,
      0.5 mg/l IAA, and 0.5 mg/l KT; the best root induction medium was solid MS medium
      at half the macronutrient concentration supplemented with 1.0 mg/l NAA, 0.4 mg/l
      IBA, and 0.1 mg/l ABT. The rooting rate was 98%. All tissue culture plants showed
      normal leaf characteristics. Tissue culture plants from two sites possessed
      higher radix ex rhizoma yield and overall productivity of matrine and oxymatrine
      than those of seed plants. CONCLUSION: Tissue culture is a rapid, effective, and
      convenient propagation method for S. tonkinensis, and the quality of S.
      tonkinensis tissue culture plants meets the requirement of quality standard of
      China Pharmacopoeia (edition 2010), the crude drug from S. tonkinensis tissue
      culture plants will be suitable for substituting the crude drug from seed plants.

PMID- 24124285
TI  - Identification of medical plants of 24 Ardisia species from China using the matK
      genetic marker.
AB  - BACKGROUND: Ardisia is a group of famous herbs in China, which has been used as
      medical plants for more than 900 years. However, the species from the genus are
      so analogous that it is difficult to discriminate them just by morphological
      characteristics. DNA barcoding is a new technique that uses a short and standard
      fragment of DNA sequences to identify species. OBJECTIVE: Choose a suitable DNA
      marker to authenticate Ardisia species. MATERIALS AND METHODS: Four markers (psbA
      trnH, internal transcribed spacer 2 [ITS2], rbcL, matK) were tested on 54 samples
      of 24 species from genus Ardisia. The success rates of polymerase chain reaction
      amplification and sequencing, differential intra- and inter-specific divergences,
      DNA barcoding gap and identification efficiency were used to evaluate the
      discrimination ability. RESULTS: The results indicate that matK has the highest
      interspecific divergence and significant differences between inter- and intra
      specific divergences, whereas psbA-trnH, ITS2 and rbcL have much lower divergence
      values. Matk possessed the highest species identification efficiency at 98.1% by
      basic local alignment search tool 1 [BLAST1], method and 91.7% by the nearest
      distance method. CONCLUSION: The matK region is a promising DNA barcode for the
      genus Ardisia.

PMID- 24124286
TI  - The stability investigation of compound Danshen injection (a traditional
      medicine) with a new high-performance liquid chromatography method.
AB  - BACKGROUND: Compound Danshen injection (CDSI, a traditional medicine) is an
      effective drug for the treatment of cardiovascular and cerebrovascular diseases.
      However, the research about its stability is absent. OBJECTIVE: A new high
      performance liquid chromatography method was developed to assay its main
      effective constituents, i.e., propanoid acid (PA), protocatechuic aldehyde (PHA),
      salvianolic acid B (SAB), salvianolic acid A (SAA), and rosmarinic acid (RA).
      Through the newly found method, the stability of CDSI was to be investigated.
      MATERIALS AND METHODS: The analysis was performed by a reverse-phase gradient
      elution using an aqueous mobile phase (containing 0.1% acetic acid) modified by
      acetonitrile, and detection was made simultaneously at 280 nm and 325 nm. The
      method was validated for accuracy, precision and limits of detection. The effects
      of some environmental storage conditions (light and temperature) on the stability
      of CDSI were investigated. RESULTS: This method is precise, simple, and
      convenient. The result showed that illumination and temperature had an obvious
      effect on CDSI's stability. SAA is the most unstable one among the five
      components. In the condition of common light, it decomposed rapidly to almost 50%
      after only 4 h, and 100% after 8 h. PA, RA, and PHA might come from Danshen, was
      also the transformed products from other components in store process. CONCLUSION:
      The result indicated that the main active constituents in CDSI suffered from the
      illumination and temperature greatly. CDSI should be stored at low temperature
      and kept away from light.

PMID- 24124287
TI  - Effect of NR-Salacia on post-prandial hyperglycemia: A randomized double blind,
      placebo-controlled, crossover study in healthy volunteers.
AB  - BACKGROUND: Salacia chinensis (S. chinensis) is widely distributed in India and
      Sri Lanka. Most of the species of genus Salacia are known to have effects on
      blood glucose levels; however, the effects of S. chinensis on glucose levels are
      seldom reported. OBJECTIVE: To evaluate the oral hypoglycemic activity of NR-
      Salacia (1000 mg extract of S. chinensis) in healthy adults. MATERIALS AND
      METHODS: Randomized, double-blind, placebo-controlled, cross-over study was
      conducted in healthy volunteers. Single dose of NR-Salacia (1000 mg extract of
      Salacia chinensis) and placebo were administered before carbohydrate-rich diet. A
      6-point plasma glucose profile was performed at different time intervals up to
      180 min. RESULTS: NR-Salacia treatment significantly lowered plasma glucose level
      at 90 min, and the percentage reduction in glucose concentration was found to be
      13.32 as compared to placebo group. A 33.85% decrease in the plasma glucose
      positive incremental area under curve (AUC) (0 to 180 min) was observed in
      comparison to placebo. No adverse events were recorded throughout the study
      period, except for some mild cases of abdominal discomforts like cramping and
      distention, vomiting, and headache in both placebo and NR-Salacia-treated groups.
      CONCLUSION: The study findings revealed that NR-Salacia lowered the post-prandial
      plasma glucose levels after a carbohydrate-rich meal and can be used as an oral
      hypoglycemic agent.

PMID- 24124288
TI  - Clinical Evaluation of Commiphora Mukul, a Botanical resin, in the Management of
      Hemorrhoids: A randomized controlled trial.
AB  - BACKGROUND: Hemorrhoids complaint is one of the most common problems in most
      society, especially in Asian countries. Current drug treatment protocols cannot
      cure the disease, and they are palliative. According to Persian traditional
      medicine, Commiphora Mukul (CM) resin is a medication choice. AIM: This
      randomized study was undertaken to evaluate the efficacy and safety of crude CM
      resin compared to a combination of lactolose and anti-hemorrhoid (LandA) in
      patients with uncomplicated hemorrhoids grade 1 and 2. MATERIALS AND METHODS:
      This trial was carried out on 99 patients with hemorrhoids, in Ghaem and Imam
      Reaza Hospitals of the Mashhad University of Medical Sciences, Iran. They
      randomly received CM 3 g/d for 4 weeks (as study group) or LandA (Lactolose syrup
      in laxative dose for 1 month and anti-hemorrhoid suppository daily for 10 days)
      as control group. Subjective and objectives variables including painful
      defecation, flatulence, constipation, gastro-esophageal reflux (GER), dyspepsia,
      proctorrhagia, anal protrusion, and colonoscopic grading were assessed before,
      immediately after, and 4 weeks after the treatment period. An intent-to-treat
      analysis was used. Safety was assessed with evaluation of clinical adverse
      effects by common toxicity criteria version 4.0. Forty-nine patients were
      assigned randomly to receive LandA and 50 to receive CM. After 4 weeks,
      flatulence, dyspepsia, GER, and colonoscopic grading scores significantly
      decreased in study group, whereas in control group constipation, painful
      defecation, and proctorrhagia showed better but not significant improvement.
      After 4-weak follow-up, the rate of constipation, and proctorrhagia also showed
      significantly improvement in study group. Constipation and proctorrhagia in
      control group recurred significantly in 4-week follow-up than after the
      treatment, whereas this recurrence in test group was not seen. CONCLUSION: CM was
      more effective than LandA in 4-week treatment of patients with uncomplicated
      hemorrhoids grade 1 and 2.

PMID- 24124289
TI  - Life is a continuous journey of transformation?

PMID- 24124290
TI  - Oral disease care or Oral health care - which one shall have priority?

PMID- 24124292
TI  - Atomic force microscopy and scanning electron microscopy evaluation of efficacy
      of scaling and root planing using magnification: A randomized controlled clinical
      study.
AB  - AIM: A randomized controlled clinical study was undertaken to evaluate the
      effectiveness of scaling and root planing (SRP) by using Magnifying Loupes (ML)
      and dental operating microscope (DOM). MATERIALS AND METHODS: A total of 90 human
      teeth scheduled for extraction from 18 patients aged between 25 and 65 years
      suffering from generalized chronic severe periodontitis were randomly assigned to
      three treatment groups. Group 1 consisted SRP performed without using
      magnification (unaided), Group 2-SRP with ML and Group 3-SRP with DOM. Following
      extractions, samples were prepared for (i) evaluation of surface topography by
      atomic force microscopy, (ii) presence of smear layer, debris by scanning
      electron microscopy (iii) elemental analysis by energy dispersive X-ray analysis.
      Data was subjected to statistical analysis using analysis of variance, post-hoc
      (Tukey-HSD) and Chi-square test. RESULTS: Statistically significant (P < 0.001)
      difference was found among the different treatment groups. Group 3 was the best
      while Group 1 was the least effective technique for SRP. Order of efficacy in
      terms of the surface was found to be - Palatal < Lingual < Distal ? Mesial <
      Buccal. Efficiency in mandibular to maxillary teeth was found to be significant
      (P < 0.05), also anterior to posterior teeth (P < 0.05). CONCLUSION:
      Magnification tools significantly enhance the efficacy of supragingival and
      subgingival SRP.

PMID- 24124291
TI  - 4-Hydroxy-2-nonenal, an oxidative stress marker in crevicular fluid and serum in
      type 2 diabetes with chronic periodontitis.
AB  - OBJECTIVE: Chronic periodontitis (CP) is a common, chronic inflammatory disease
      initiated by bacteria, which has an increased prevalence and severity in patients
      with type 2 diabetes mellitus (t2 DM). A variety of reactive oxygen species are
      able to cause direct damage to proteins, deoxyribonucleic acid, carbohydrates and
      lipids. Lipid peroxidation is always combined with the formation of reactive
      aldehydes like 4-Hydroxy-2-nonenal (HNE). The purpose of this study was to
      determine the presence of the HNE-His adducts levels in serum and gingival
      crevicular fluid (GCF) in t2 DM among CP subjects and to find an association, if
      any. MATERIALS AND METHODS: A total of 40 subjects (20 males and 20 females) were
      selected based on their clinical parameters into three groups: Group 1 (10
      healthy), Group 2 (15 subjects, CP without t2 DM), Group 3 (15 subjects, CP with
      t2 DM). Serum and GCF samples were collected to estimate the levels of the HNE
      His adducts by the enzyme linked immunosorbent assay. RESULTS: The mean HNE-His
      adducts concentration both in serum and GCF was highest for Group 3 followed by
      Group 2 and least in Group 1. CONCLUSIONS: All samples in each group tested
      positive for HNE-His adducts assay. Serum and GCF HNE-His adducts concentration
      both in t2 DM with CP and non-diabetic CP subjects were higher than the healthy
      controls. Further large scale longitudinal studies should be carried out to
      confirm positive correlations.

PMID- 24124293
TI  - Incidence of post-operative pain following single visit endodontics in vital and
      non-vital teeth: An in vivo study.
AB  - This clinical study was conducted to compare the post-operative pain following
      single visit endodontics in vital and non-vital teeth, with and without
      periapical radiolucency. A total of 60 adult patients requiring root canal
      therapy in anterior and premolar teeth were selected for this study. Single
      sitting root canal treatment was carried out and the subjects were recalled after
      2 weeks and instructed to fill out a series of self-report questionnaires for
      responses about pain in the interim after 1 day, 2 day, 3 day, 1 week and 2
      weeks. In vital teeth (Group I) 60% of the treated cases had pain, of which 36%
      had mild pain (non-significant) and 24% had moderate pain (significant). In non
      vital teeth without periapical radiolucency (Group II) 64% of cases had pain, of
      which 48% had mild pain (non-significant) and 16% had moderate pain
      (significant). In non-vital teeth with periapical radiolucency (Group III) 32% of
      the cases had pain of which 24% had mild pain (non-significant) and 8% had
      moderate pain (significant). None of the teeth in any of the groups had severe
      pain. There was no statistical difference between incidence of pain in vital and
      non-vital teeth without periapical radiolucency. Non-vital teeth with periapical
      radiolucency exhibited relatively less pain as compared with non-vital teeth
      without periapical radiolucency, but the pain continued in a significant percent
      of teeth even after 2 weeks. Pain incidence dropped significantly within a period
      of 1 day to 2 weeks in vital teeth and non-vital teeth without periapical
      radiolucency. There was a tendency for less incidence of significant pain after a
      single visit root canal treatment in these groups. Results obtained were
      comparable with those obtained by several investigators. 

PMID- 24124294
TI  - Estimation of prostaglandin E2 levels in gingival crevicular fluid in periodontal
      health, disease and after treatment.
AB  - BACKGROUND AND OBJECTIVES: Initial research has shown a positive correlation
      between the severity of periodontal disease (PD) and prostaglandin E2 (PGE2)
      concentrations in gingival crevicular fluid (GCF). However, there are no enough
      reports to correlate the PGE2 concentrations in GCF in periodontal health,
      disease and after treatment. Hence, the present study is aimed to estimate the
      levels of PGE2 in GCF in periodontal health, disease and after periodontal
      therapy. MATERIALS AND METHODS: A periodontal examination and collection of GCF
      by extracrevicular method was performed in 25 subjects selected randomly and
      categorized into three groups on the basis of plaque index, gingival index,
      probing pocket depth and clinical attachment level. Group I (healthy) consists of
      10 subjects, Group II (chronic periodontitis) consists of 15 patients and Group
      III (after treatment group) consists of 15 patients of Group II. PGE2 levels were
      estimated in GCF samples by using the enzyme linked immunosorbent assay. RESULTS:
      All clinical parameters improved significantly after therapy (P < 0.001). PGE2
      was detected in all the samples. Highest mean PGE2 concentrations in GCF were
      obtained for Group II while the lowest concentrations were seen in Group I and
      Group III. Statistically significant difference was found between the levels of
      PGE2 at Group-II and Group-III (P < 0.05). CONCLUSION: There is a substantial
      increase in the concentrations of PGE2 as PD progresses. Since PGE2 levels in GCF
      are positively correlated with gingival index, plaque index, probing pocket
      depths and clinical attachment levels, PGE2 may be considered as a Novel
      Biomarker in PD progression. However, controlled, longitudinal studies are needed
      to confirm this possibility.

PMID- 24124295
TI  - Assessment of clinical outcomes of Roth and MBT bracket prescription using the
      American Board of Orthodontics Objective Grading System.
AB  - BACKGROUND: There is always a need to assess whether small changes in bracket
      prescription can lead to visually detectable differences in tooth positions.
      However, with little clinical evidence to show advantages of any of the popularly
      used bracket systems, orthodontists are forced to make clinical decisions with
      little scientific guidance. AIM: To compare the orthodontic cases finished with
      Roth and MBT prescription using American Board of Orthodontics-Objective Grading
      System (ABO-OGS). SETTINGS AND DESIGN: Department of Orthodontics, Post-graduate
      dental college, retrospective cross-sectional study. MATERIALS AND METHODS: Forty
      patients selected were divided into two groups of 20 patients each finished with
      straight wire appliance using Roth and MBT prescription, respectively. The
      examiner ability was assessed and calibrated by one of the ABO certified
      clinician to grade cases using the OGS. STATISTICAL ANALYSIS: Unpaired student t
      test was used and P < 0.05 was accepted as significant. RESULTS AND CONCLUSIONS:
      MBT bracket group had a lower score of 2.60 points in buccolingual inclination
      and lower score of 1.10 points in occlusal contact category that was
      statistically significant when compared with Roth group. The difference in total
      ABO-OGS score was 2.65 points showing that the outcome for the MBT prescription
      was better than that of the Roth prescription, which is statistically
      significant, but with little or no clinical significance. It can be concluded
      that use of either one of the Roth and MBT bracket prescriptions have no impact
      to the overall clinical outcome and quality of treatment entirely depends on
      clinician judgment and experience.

PMID- 24124296
TI  - The effect of pouring time on the dimensional accuracy of casts made from
      different irreversible hydrocolloid impression materials.
AB  - AIMS AND OBJECTIVES: To determine the time dependent accuracy of casts made from
      three different irreversible hydrocolloids. MATERIALS AND METHODS: The effect of
      delayed pouring on the accuracy of three different irreversible hydrocolloid
      impression materials - Regular set CA 37(Cavex, The Netherlands), regular set
      chromatic (Jeltrate, Dentsply), and fast set (Hydrogum soft, Zhermack Clinical)
      was investigated. A brass master die that contained two identical posts
      simulating two complete crown-tapered abutment preparations with reference
      grooves served as a standardized master model. A total of 120 impressions were
      made using specially prepared stock-perforated brass tray with 40 impressions of
      each material. The impressions were further sub-grouped according to four
      different storage time intervals: 0 min (immediately), 12 min, 30 min, and 1 h.
      The impressions were stored at room temperature in a zip-lock plastic bag.
      Interabutment and intraabutment distances were measured in the recovered stone
      dies (Type IV, Kalrock) using a profile projector with an accuracy of 0.001 mm.
      The data so obtained was analyzed statistically. RESULTS: Results of this study
      showed no statistically significant differences in the accuracy of casts obtained
      at different time intervals. CONCLUSION: Because it is not always possible to
      pour the impression immediately in routine clinical practice, all irreversible
      hydrocolloid materials studied could be stored in a zip-lock plastic bag for upto
      1 h without any significant distortion.

PMID- 24124297
TI  - Evaluating the clinical and esthetic outcome of apically positioned flap
      technique in augmentation of keratinized gingiva around dental implants.
AB  - PURPOSE: Dental implants though a successful treatment modality there exists
      controversies regarding the relationship between the adequacy of the keratinized
      gingiva (KG) and peri-implant health. The presence of an adequate amount of peri
      implant KG reduces gingival inflammation and hence soft-tissue augmentation
      should be frequently considered. Among the various periodontal plastic surgical
      procedures, the apically displaced flap increases the width of keratinized tissue
      with reduced patient morbidity. The current study aims at evaluating the esthetic
      improvement in KG around dental implants applying apically positioned flap (APF)
      technique. MATERIALS AND METHODS: A total of 10 endosseous dental implants were
      placed in eight systemically healthy patients. APF surgery was performed at the
      implant site on the buccal aspect either at the time of implant placement (one
      stage surgical protocol) or during the implant recovery stage (two stage surgical
      protocols) for increasing the width of KG and reviewed until 12 weeks post
      operatively. The width of KG was evaluated at baseline and at the end of 12 weeks
      after surgery. Paired t-test was performed to evaluate the changes in the width
      of KG at baseline and at 12 weeks post-operatively. In addition, soft-tissue
      esthetic outcome was assessed by using visual analog scale (VAS). RESULTS: The
      mean width of KG at baseline was 1.47 mm and 12 weeks post-operatively was 5.42
      mm. The gain in KG from baseline was 3.95 mm with the P value of 0.000, which was
      highly statistically significant. The assessment of esthetic outcome using VAS
      gave an average score of 7.1 indicating good esthetics. CONCLUSION: The technique
      of APF yielded a significant improvement in keratinized tissue, which is both
      functionally and esthetically acceptable.

PMID- 24124298
TI  - A cephalometric study to ascertain the use of nasion as a guide in locating the
      position of orbitale as an anterior reference point among a population of South
      Coastal Karnataka.
AB  - CONTEXT: To ascertain the use of nasion as a guide in locating the position of
      orbitale as an anterior reference point in the face-bow transfer records in
      individuals having different facial types. AIMS: This study evaluated the
      distance from the nasion to the orbitale using cephalometric measurements to
      ascertain the use of nasion as a guide in locating the position of orbitale as an
      anterior reference point in individuals having different facial types among a
      population of South Coastal Karnataka. SUBJECTS AND METHODS: Anthropometric
      measurements were made on 61 subjects and they were classified into mesoprosopic,
      euryprosopic and leptoprosopic facial type groups based upon the prosopic index.
      Lateral cephalometric radiographs were taken and nasion to orbitale distance was
      measured. The collected data was tabulated and statistically analyzed.
      STATISTICAL ANALYSIS USED: The statistical test carried out was the analysis of
      variance test and correlations were checked for using Pearson's correlation test.
      RESULTS: The study found the mean distance from nasion to orbitale was 24.25 mm
      with a standard deviation 4.26 mm. A good correlation was found between prosopic
      index and nasion to orbitale distance. No statistically significant variation in
      nasion to orbitale distance in individuals of different facial types was found.
      CONCLUSIONS: Although, variation exists it was not statistically significant.
      However, since a large range of measurements were found, prior evaluation using
      cephalometric radiographs may be necessary in certain individuals.

PMID- 24124299
TI  - Surface remineralization potential of casein phosphopeptide-amorphous calcium
      phosphate on enamel eroded by cola-drinks: An in-situ model study.
AB  - AIM: The aim of this study was to investigate the remineralization potential of
      casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on enamel eroded by
      cola drinks. SUBJECTS AND METHODS: A total of 30 healthy subjects were selected
      from a random sample of 1200 children and divided into two groups of 15 each
      wherein calcium and phosphorus analyses and scanning electron microscope (SEM)
      analysis was carried out to investigate the remineralization of enamel surface. A
      total of 30 non-carious premolar teeth were selected from the human tooth bank
      (HTB) to prepare the in-situ appliance. Three enamel slabs were prepared from the
      same. One enamel slab was used to obtain baseline values and the other two were
      embedded into the upper palatal appliances prepared on the subjects' maxillary
      working model. The subjects wore the appliance after which 30 ml cola drink
      exposure was given. After 15 days, the slabs were removed and subjected to
      respective analysis. STATISTICAL ANALYSIS USED: Means of all the readings of
      soluble calcium and phosphorous levels at baseline,post cola-drink exposure and
      post cpp-acp application were subjected to statistical analysis SPSS11.5 version.
      Comparison within groups and between groups was carried out using ANOVA and F
      values at 1% level of significance. RESULTS: Decrease in calcium solubility of
      enamel in the CPP-ACP application group as compared to post-cola drink exposure
      group (P < 0.05) was seen. Distinctive change in surface topography of enamel in
      the post-CPP-ACP application group as compared to post-cola drink exposure group
      was observed. CONCLUSION: CPP-ACP significantly promoted remineralization of
      enamel eroded by cola drinks as revealed by significant morphological changes
      seen in SEM magnification and spectrophotometric analyses.

PMID- 24124300
TI  - Comparison of the diagnostic accuracy of direct digital radiography system,
      filtered images, and subtraction radiography.
AB  - BACKGROUND: TO COMPARE THE DIAGNOSTIC ACCURACY OF THREE DIFFERENT IMAGING
      SYSTEMS: Direct digital radiography system (DDR-CMOS), four types of filtered
      images, and a priori and a posteriori registration of digital subtraction
      radiography (DSR) in the diagnosis of proximal defects. MATERIALS AND METHODS:
      The teeth were arranged in pairs in 10 blocks of vinyl polysiloxane, and proximal
      defects were performed with drills of 0.25, 0.5, and 1 mm diameter. Kodak RVG
      6100 sensor was used to capture the images. A posteriori DSR registrations were
      done with Regeemy 0.2.43 and subtraction with Image Tool 3.0. Filtered images
      were obtained with Kodak Dental Imaging 6.1 software. Images (n = 360) were
      evaluated by three raters, all experts in dental radiology. RESULTS: Sensitivity
      and specificity of the area under the receiver operator characteristic (ROC)
      curve (Az) were higher for DSR images with all three drills (Az = 0.896, 0.979,
      and 1.000 for drills 0.25, 0.5, and 1 mm, respectively). The highest values were
      found for 1-mm drills and the lowest for 0.25-mm drills, with negative filter
      having the lowest values of all (Az = 0.631). CONCLUSION: The best method of
      diagnosis was by using a DSR. The negative filter obtained the worst results.
      Larger drills showed the highest sensitivity and specificity values of the area
      under the ROC curve.

PMID- 24124301
TI  - Moisture-tolerant resin-based sealant: A boon.
AB  - BACKGROUND AND OBJECTIVES: Pit and fissure sealants are highly effective in
      preventing occlusal caries. The present study clinically evaluated and compared
      the retention and development of caries when sealed with moisture-tolerant resin
      based sealant, conventional resin-based sealant with and without a bonding agent,
      and Glass Ionomer Cement Sealant in young permanent teeth. MATERIALS AND METHODS:
      A total of 80 healthy cooperative children aged 6-9 years who were at high caries
      risk with all four newly erupted permanent first molars were included in the
      study. Teeth were divided into 4 groups using a full-factorial design, and each
      of the molars was sealed with the four different sealant material. Evaluation of
      sealant retention and development of caries was performed at 6 and 12 months
      using Modified Simonsen's criteria. The data obtained were tabulated and
      subjected to statistical analysis using Kruskal-Wallis Test and Mann-Whitney
      Test. RESULT AND CONCLUSION: The result from the present study indicated that
      moisture-tolerant resin-based sealant could be successfully used as a pit and
      fissure sealant because its hydrophilic chemistry makes it less technique
      sensitive and simplifies the sealant application procedure.

PMID- 24124302
TI  - Protostylid: A case series.
AB  - Human jaws and teeth display a high degree of morphological individuality as they
      represent personal, family and population characteristics. A protostylid is a
      supernumerary or accessory cusp located on the mesial half of the buccal surface
      on the molars that may seldom pose problems while its presence may not be a cause
      for alarm in most instances. This case report presents a rare finding of
      protostylid on the buccal surface of the primary molars in 4 children. From the
      perspective of forensic dentistry, this morphological feature, though uncommon,
      may be useful for classification and identification of victims in mass
      causalities and bite marks on bodies or inanimate objects. 

PMID- 24124303
TI  - Removable molar power arm.
AB  - Attachment of force elements from the gingival hook of maxillary molar tubes
      during the retraction of the anterior teeth is very common in orthodontic
      practice. As the line of force passes below the center of resistance (CR) of
      molar, it results its mesial tipping and also anchorage loss. To overcome this
      problem, the line of force should pass along the CR of molar. This article
      highlights a method to overcome this problem by attaching a removable power arm
      to the headgear tube of molar tube during the retraction of the anterior teeth. 

PMID- 24124304
TI  - Cherubism: Report of a case.
AB  - Cherubism is an uncommon fibro-osseous disorder of the jaw that presents with
      varying degrees of involvement and tendency towards spontaneous remission.
      Children are normal at birth and the expanding jaw is noticed within the first
      year of life becoming progressively larger until the beginning of adolescence.
      Lesions are characterized by replacement of bone with fibrovascular tissue
      containing abundant multinucleated giant cells. Here, we describe a case of
      cherubism in a 4-year-old child with swelling on both sides of mandible with
      clinic radiographic features and suggestions for therapy. 

PMID- 24124305
TI  - Sturge-Weber syndrome with pyogenic granuloma.
AB  - Vascular lesions represent one of the rare disorders affecting overall quality of
      life of a child. A wide variety of these conditions are known, ranging from a
      simple nevus to life-threatening hemangiomas. These conditions make the treatment
      options more complex due to the fear of uncontrollable bleeding. The present case
      is one of the rare combinations of Sturge-Weber syndrome and pyogenic granuloma.
      Conditions of importance and treatment options keeping hemangioma in mind are
      discussed. 

PMID- 24124306
TI  - Clinical spectrum of Silver - Russell syndrome.
AB  - Silver - Russell syndrome is a clinically and genetically heterogenous condition
      characterized by severe intrauterine and postnatal growth retardation,
      craniofacial disproportion and normal intelligence downward curvature of the
      corner of the mouth, syndactyly and webbed fingers. Diagnosis of Silver - Russell
      syndrome remains clinical; no definite etiology or specific tests have been
      established. In the recent years, it has been shown that more than 38% of
      patients have hypomethylation in the imprinting control region 1 of 11p15 and one
      tenth of patients carry a maternal uniparental disomy of chromosome seven. The
      pathophysiological mechanisms resulting in the Silver - Russell phenotype remain
      unknown despite the recent progress in deciphering the molecular defects
      associated with this condition. This case report describes the clinical features
      of Silver - Russell syndrome in a father and daughter. 

PMID- 24124307
TI  - Bimaxillary unilateral gingival fibromatosis with localized aggressive
      periodontitis (eating the tooth at the same table).
AB  - This case reports a unique presentation of two different clinical entities amidst
      few similarities and differences. Usually, aggressive periodontitis and gingival
      fibromatosis occur independently. Their simultaneous occurrence is rarely found.
      This report deals with the clinical features and management aspect of such a
      case. 

PMID- 24124308
TI  - Management of impacted all canines with surgical exposure and alignment by
      orthodontic treatment.
AB  - Canine impaction is a dental problem very often encountered in orthodontic
      practice. After the third molar, the canine is the most frequently impacted
      tooth. Bringing the impacted canine into a normal position is important for
      functional occlusion and the final esthetics of the orthodontic treatment. This
      article illustrates a peculiar case, in which all four permanent canines
      maintained their unerupted status at age of 16 years. All four impacted canines
      were surgically exposed, attachment bonded, traction given with K-9 spring and
      ideally positioned with fixed orthodontic mechanotherapy. 

PMID- 24124309
TI  - Oncologic profile of maxillary odontogenic myxoma: A rare case.
AB  - Odontogenic myxoma (OM) is an ectomesenchyme derived neoplasm, almost exclusively
      found in jaws. This article presents a maxillary OM with a brief review of the
      molecular and proteomic antecedents of OMs, capturing its histopathogenesis. 

PMID- 24124310
TI  - Lip reposition surgery: A new call in periodontics.
AB  - "Gummy smile" is a major concern for a large number of patients visiting the
      dentist. Esthetics has now become an integral part of periodontal treatment plan.
      This article presents a case of a gummy smile in which esthetic correction was
      achieved through periodontal plastic surgical procedure wherein a 10-12 mm of
      partial-thickness flap was dissected apical to mucogingival junction followed by
      approximation of the flaps. This novel technique gave excellent post-operative
      results with enormous patient satisfaction. This surgical chair-side procedure
      being one of its kinds with outstanding results is very rarely performed by
      Periodontists. Thus, a lot of clinical work and literature review with this
      surgical technique is required. To make it a routine surgical procedure this
      technique can be incorporated as a part of periodontal plastic surgery in the
      text. Hence, we have put forward experience of a case with critical analysis of
      the surgical technique including the limitations of the technique. 

PMID- 24124311
TI  - Osteosarcoma of mandible: Detailed radiographic assessment of a case.
AB  - Osteosarcoma (OS) is a malignant connective tissue tumor originating from bone
      and is the most common primary bone malignancy of long bones but seldom arises in
      jaw bones. Osteosarcoma of jaws is frequently seen arising in the second and
      third decade as compared to earlier occurrences in other bones and show a slight
      predilection for body of mandible. It is a highly malignant tumor with varied
      radiographic features. We present a case with detailed radiographic assessment
      using intraoral radiograph, computed tomography (CT), 3-D CT, CT angiography
      techniques and histological evaluation. 

PMID- 24124312
TI  - Habitual biting of oral mucosa: A conservative treatment approach.
AB  - Chronic biting of oral mucosa is an innocuous self inflicted injury, commonly
      seen in children suffering from developmental and psychological problems and has
      rarely been reported in normal unaffected individuals. The management strategies
      vary from counseling, prescription of sedatives to different prosthetic shields.
      The paper highlights the efficacy of a simple approach using soft mouth guard in
      the management of self inflicted lesions due to habitual biting of oral mucosa in
      two normal healthy children. 

PMID- 24124313
TI  - Surgical treatment of odontogenic myxoma and facial deformity in the same
      procedure.
AB  - Odontogenic myxoma (OM) is an uncommon benign tumor with aggressive and invasive
      behavior. Predominant symptoms are usually slow and painless swelling, sometimes
      resulting in perforation of the cortical borders of the affected bone. In this
      paper, a case report of a patient with an OM on the right maxillary sinus and a
      vertical excess of maxilla will be presented. The treatment chosen was tumor
      resection in association with orthognathic surgery with biomodels assessment for
      surgical planning. A 3-year follow-up showed disease free and stability of the
      new position of maxilla. The international literature is evaluated to discuss
      this case report. 

PMID- 24124314
TI  - Implant rehabilitation of partial maxillectomy edentulous patient.
AB  - Edentulous patients with maxillectomy defects present a significant challenge for
      prosthetic rehabilitation and the adaptive capabilities of the patient as
      retention is highly compromised. Hence, the option of using endosseous implants
      to increase obturator retention has been used. A patient of mucormycosis of the
      left maxilla was treated with surgical excision. After satisfactory healing,
      definitive implant supported magnet retained prosthesis was fabricated for the
      patient. Implants with magnetic units offer a practical method of improving the
      retention of obturators provided acceptable prosthetic protocols are followed for
      the rehabilitation. 

PMID- 24124315
TI  - Retraction notice.

PMID- 24124316
TI  - Masson's hemangioma: A rare intraoral presentation.
AB  - An otherwise healthy 19-year-old female patient had painless swelling in her left
      buccal mucosa. No precipitating factors were identified. Pathological analysis
      demonstrated the mass to be a Masson's hemangioma, a papillary proliferation of
      thin-walled capillaries intimately associated with thrombus. A very rare tumor
      occurring in oral cavity with only 80 cases being published in literature until
      date. 

PMID- 24124317
TI  - Telescopic overdenture: Perio-prostho concern for advanced periodontitis.
AB  - The crown- and sleeve-coping denture is a removable prosthesis that is supported
      by both selectively retained teeth and the residual ridge or mucosa. It is a
      versatile and successful means of achieving long-term restoration of a partially
      edentulous jaw. Insertion and removal of the denture and routine oral hygiene are
      easy to perform. The beneficial results of this form of treatment can be
      considered for a wide variety of clinical applications for the severely advanced
      periodontitis case. This paper presents a case report on the prosthetic
      rehabilitation of a partially edentulous patient with a telescopic overdenture
      for the mandible and complete denture for the maxilla. 

PMID- 24124318
TI  - A rare presentation of hybrid odontogenic tumor involving calcifying cystic
      odontogenic tumor and plexiform ameloblastoma.
AB  - A hybrid odontogenic tumor comprising two distinct lesions is extremely rare. We
      presented a hybrid odontogenic tumor composed of a calcifying cystic odontogenic
      tumor (CCOT) and a plexiform ameloblastoma. This tumor was observed in the
      anterior area of the mandible of a 17-year-old Indian male. Masses of ghost
      epithelial cells with the characteristics of CCOT were seen in the lining of the
      cyst. The odontogenic epithelia with the features of plexiform ameloblastoma were
      also observed. 

PMID- 24124319
TI  - Pachyonychia congenita tarda: A rare case report.
AB  - Pachyonychia congenita is a rare, but well-characterized autosomal dominant
      disorder of keratinization. It usually begins within the first few months of
      life. Here, we are presenting a rare case, which started at the age of 10 years
      of life and is known as pachyonychia congenita tarda. The case is being reported
      for its rarer occurrence as the patient had oral leukokeratosis and angular
      cheilosis present in the same type of the syndrome (Jadassohn-Lewandowsky
      syndrome), which is still uncommon. 

PMID- 24124320
TI  - Platelet-rich fibrin-mediated revitalization of immature necrotic tooth.
AB  - Contemporary studies have shown that the regeneration of tissues and root
      elongation is possible in necrotic immature permanent teeth. The purpose of this
      case report is to add a new vista in regenerative endodontic therapy by using
      platelet rich fibrin for revitalization of immature non vital tooth. An 11year
      old boy with the history of trauma was diagnosed with the pulpal necrosis and
      symptomatic apical periodontitis in tooth #21. Intra oral periapical radiograph
      showed open apex and associated immature supernumerary tooth with respect to
      tooth #21. Access preparation and minimal instrumentation was done to remove
      necrotic debris under copious irrigation with 2.5% sodium hypochlorite. Triple
      antibiotic paste was packed in the canal for four weeks. During second visit, 5
      mL of whole blood was drawn from the medial cubital vein of the patient and blood
      was then subjected to centrifugation at 2400 rpm for 12 minutes for the
      preparation of Platelet rich fibrin (PRF) utilizing Choukroun's method. Triple
      antibiotic paste was removed and canal was dried. PRF clot was pushed to the
      apical region of tooth #21 using hand pluggers. Three milimetres of Mineral
      trioxide (MTA) was placed in cervical part of the root canal and permanent
      restoration was done three days later. Clinical examination at 6 and 12 months
      revealed no sensitivity to percussion and palpation in tooth #21and it responded
      positively to both electric pulp and cold tests. Radiographic examination showed
      resolution of periapical rarefaction, further root development and apical closure
      of the tooth #21 and its associated supernumerary tooth. On the basis of
      successful outcome of the present case it can be stated that PRF clot may serve
      as a scaffold for regeneration of necrotic immature teeth. 

PMID- 24124321
TI  - Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4
      related diseases?
AB  - In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular
      lesions consisting of abundant infiltration of lymphocytes and IgG4-positive
      plasma cells and fibrosis are seen in various organs. Although infiltration of
      many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and
      major duodenal papilla of patients with autoimmune pancreatitis, it cannot be
      diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the
      following is observed in these lesions: a mass-like formation; dense fibrosis; or
      obliterative phlebitis. Based on our review of the literature, there appear to be
      two types of IgG4-related gastrointestinal disease. One is a gastrointestinal
      lesion showing marked thickening of the wall of the esophagus and stomach,
      consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma
      cells, which usually show submucosal spreading. The other is an IgG4-related
      pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and
      major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4
      related gastrointestinal lesions that are not associated with other IgG4-RD
      appear to be difficult to diagnose. It is of utmost importance to rule out
      malignancy. However, these lesions may respond to steroid therapy. To avoid
      unnecessary resection, IgG4-related gastrointestinal diseases should be
      considered in the differential diagnosis. 

PMID- 24124322
TI  - Pathophysiology, epidemiology, classification and treatment options for
      polycystic liver diseases.
AB  - Polycystic liver diseases (PLD) represent a group of genetic disorders in which
      cysts occur in the liver (autosomal dominant polycystic liver disease) or in
      combination with cysts in the kidneys (autosomal dominant polycystic kidney
      disease). Regardless of the genetic mutations, the natural history of these
      disorders is alike. The natural history of PLD is characterized by a continuous
      increase in the volume and the number of cysts. Both genders are affected;
      however, women have a higher prevalence. Most patients with PLD are asymptomatic
      and can be managed conservatively. Severe symptoms can affect 20% of patients who
      develop massive hepatomegaly with compression of the surrounding organs. Rrarely,
      patients with PLD suffer from acute complications caused by the torsion of
      hepatic cysts, intraluminal cystic hemorrhage and infections. The most common
      methods for the diagnosis of PLD are cross sectional imaging studies. Abdominal
      ultrasound and computerized tomography are the two most frequently used
      investigations. Magnetic resonance imaging is more sensitive and specific, and it
      is a valuable test for patients with intravenous contrast allergies or renal
      dysfunction. Different treatment modalities are available to physicians caring
      for these patients. Medical treatment has been ineffective. Percutaneous
      sclerotherapy, trans-arterial embolization, cyst fenestration, hepatic resection
      and liver transplantation are indicated to specific groups of patients and have
      to be tailored according to the extent of disease. This review outlines the
      current knowledge of the pathophysiology, clinical course, diagnosis and
      treatment strategies of PLD. 

PMID- 24124323
TI  - Overlap of functional heartburn and gastroesophageal reflux disease with
      irritable bowel syndrome.
AB  - Several studies indicate a significant degree of overlap between irritable bowel
      syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both
      functional heartburn (FH) and IBS are functional digestive disorders that may
      occur in the same patients. However, data establishing a solid link between FH
      and IBS are lacking, mainly because the clinical definition of FH has undergone
      substantial changes over the years. The available literature on the overlap
      between GERD or FH and IBS highlights considerable heterogeneity in terms of the
      criteria and diagnostic procedures used to assess heartburn and IBS. In
      particular, several epidemiological studies included patients with concomitant
      IBS and GERD without any attempt to distinguish FH (as defined by the Rome III
      criteria) from GERD via pathophysiological investigations. Independent of these
      critical issues, there is preliminary evidence supporting a significant degree of
      FH-IBS overlap. This underscores the need for studies based on updated diagnostic
      criteria and accurate pathophysiological classifications, particularly to
      distinguish FH from GERD. This distinction would represent an essential starting
      point to achieving a better understanding of pathophysiology in the subclasses of
      patients with GERD and FH and properly assessing the different degrees of overlap
      between IBS and the subcategories of heartburn.The present review article intends
      to appraise and critically discuss current evidence supporting a possible
      concomitance of GERD or FH with IBS in the same patients and to highlight the
      pathophysiological relationships between these disorders. 

PMID- 24124324
TI  - Criteria for the diagnosis and severity stratification of acute pancreatitis.
AB  - Recent diagnostic and therapeutic progress for severe acute pancreatitis (SAP)
      remarkably decreased the case-mortality rate. To further decrease the mortality
      rate of SAP, it is important to precisely evaluate the severity at an early
      stage, and initiate appropriate treatment as early as possible. Research
      Committee of Intractable Diseases of the Pancreas in Japan developed simpler
      criteria combining routinely available data with clinical signs. Severity can be
      evaluated by laboratory examinations or by clinical signs, reducing the defect
      values of the severity factors. Moreover, the severity criteria considered
      laboratory/clinical severity scores and contrast-enhanced computed tomography (CE
      CT) findings as independent risk factors. Thus, CE-CT scans are not necessarily
      required to evaluate the severity of acute pancreatitis. There was no fatal case
      in mild AP diagnosed by the CE-CT severity score, whereas case-mortality rate in
      those with SAP was 14.8%. Case-mortality of SAP that fulfilled both the
      laboratory/clinical and the CE-CT severity criteria was 30.8%. It is recommended,
      therefore, to perform CE-CT examination to clarify the prognosis in those
      patients who were diagnosed as SAP by laboratory/clinical severity criteria.
      Because the mortality rate of these patients with SAP is high, such patients
      should be transferred to advanced medical units. 

PMID- 24124325
TI  - Achalasia: a review of clinical diagnosis, epidemiology, treatment and outcomes.
AB  - Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in
      deranged oesophageal peristalsis and loss of lower oesophageal sphincter
      function. Historically, annual achalasia incidence rates were believed to be low,
      approximately 0.5-1.2 per 100000. More recent reports suggest that annual
      incidence rates have risen to 1.6 per 100000 in some populations. The aetiology
      of achalasia is still unclear but is likely to be multi-factorial. Suggested
      causes include environmental or viral exposures resulting in inflammation of the
      oesophageal myenteric plexus, which elicits an autoimmune response. Risk of
      achalasia may be elevated in a sub-group of genetically susceptible people.
      Improvement in the diagnosis of achalasia, through the introduction of high
      resolution manometry with pressure topography plotting, has resulted in the
      development of a novel classification system for achalasia. This classification
      system can evaluate patient prognosis and predict responsiveness to treatment.
      There is currently much debate over whether pneumatic dilatation is a superior
      method compared to the Heller's myotomy procedure in the treatment of achalasia.
      A recent comparative study found equal efficacy, suggesting that patient
      preference and local expertise should guide the choice. Although achalasia is a
      relatively rare condition, it carries a risk of complications, including
      aspiration pneumonia and oesophageal cancer. The risk of both squamous cell
      carcinoma and adenocarcinoma of the oesophagus is believed to be significantly
      increased in patients with achalasia, however the absolute excess risk is small.
      Therefore, it is currently unknown whether a surveillance programme in achalasia
      patients would be effective or cost-effective. 

PMID- 24124326
TI  - Molecular epidemiology and putative origin of hepatitis C virus in random
      volunteers from Argentina.
AB  - AIM: To study the subtype prevalence and the phylogenetic relatedness of
      hepatitis C virus (HCV) sequences obtained from the Argentine general population,
      a large cohort of individuals was analyzed. METHODS: Healthy Argentinian
      volunteers (n = 6251) from 12 provinces representing all geographical regions of
      the country were studied. All parents or legal guardians of individuals younger
      than 18 years provided informed written consent for participation. The
      corresponding written permission from all municipal authorities was obtained from
      each city or town where subjects were to be included. HCV RNA reverse
      transcription-polymerase chain reaction products were sequenced and
      phylogenetically analyzed. The 5' untranslated region (5'UTR) was used for RNA
      detection and initial genotype classification. The NS5B polymerase region,
      encompassing nt 8262-8610, was used for subtyping. RESULTS: An unexpectedly low
      prevalence of HCV infection in the general population (0.32%) was observed. Our
      data contrasted with previous studies that reported rates ranging from 1.5% to
      2.5%, mainly performed in selected populations of blood donors or vulnerable
      groups. The latter values are in keeping with the prevalence reported by the 2007
      Argentinian HCV Consensus (approximately 2%). HCV subtypes were distributed as
      follows: 1a (25%), 1b (25%), 2c (25%), 3a (5%), and 2j (5%). Two isolates
      ascribed either to genotype 1 (5%) or to genotype 3 (5%) by 5'UTR phylogenetic
      analysis could not be subtyped. Subtype 1a sequences comprised a highly
      homogeneous population and clustered with United States sequences. Genotype 1b
      sequences represented a heterogeneous population, suggesting that this genotype
      might have been introduced from different sources. Most subtype 2c sequences
      clustered close to the 2c reported from Italy and Southern France. CONCLUSION:
      HCV has a low prevalence of 0.32% in the studied general population of Argentina.
      The pattern of HCV introduction and transmission in Argentina appears to be a
      consequence of multiple events and different for each subtype.

PMID- 24124327
TI  - Aberrant TGF-beta1 signaling contributes to the development of primary biliary
      cirrhosis in murine model.
AB  - AIM: To investigate whether transforming growth factor-beta1 (TGF-beta1)
      signaling pathway is involved in the pathogenesis of primary biliary cirrhosis
      (PBC). METHODS: A murine model of PBC was developed by injection of polyinosinic
      polycytidylic acids (poly I: C) in C57BL/6 mice, and the liver expressions of TGF
      beta1, TGF-beta receptor I (TbetaRI), TGF-beta receptor II (TbetaRII), p-Smad2/3,
      monoclonal alpha-smooth muscle actin antibody (alpha-SMA) and alpha1 (I) collagen
      in the mouse model and control mice were evaluated by immunohistochemistry,
      immunoblotting and real-time polymerase chain reaction (RT-PCR). Lymphocyte
      subsets in liver were analyzed using flow cytometry. RESULTS: The mouse model had
      several key phenotypic features of human PBC, including elevated levels of
      alkaline phosphatase, antimitochondrial antibodies, portal bile ducts
      inflammation, and progressive collagen deposition. Compared with control mice,
      protein and mRNA levels of TGF beta1, TbetaRI, TbetaRII, p-Smad2/3, alpha-SMA and
      alpha1 (I) collagen in liver (1.7 +/- 0.4 vs 8.9 +/- 1.8, 0.8 +/- 0.2 vs 5.1 +/-
      1.5, 0.6 +/- 0.01 vs 5.1 +/- 0.1, 0.6 +/- 0.3 vs 2.0 +/- 0.3, 0.9 +/- 0.4 vs 3.4
      +/- 0.6, 0.8 +/- 0.4 vs 1.7 +/- 0.3, 1.1 +/- 1.2 vs 11.8 +/- 0.6, P < 0.05), and
      the total number and percentage of CD4+ CD25+ FOXP3+ and CD8+ lymphocytes (0.01
      +/- 0.001 vs 0.004 +/- 0.00, 0.12 +/- 0.04 vs 0.52 +/- 0.23, P < 0.01) were
      higher in the mouse model. CONCLUSION: TGFbeta1 might play a dual role in the
      development of PBC: it suppresses inflammatory response but operates to enhance
      fibrogenesis. The aberrant activity of TGF-beta1 signaling contributes to the
      development of PBC.

PMID- 24124328
TI  - Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot
      study.
AB  - AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease
      (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients.
      METHODS: Patients with initial diagnosis of celiac disease as confirmed by
      positive serology with subtotal or total villous atrophy on duodenal biopsies who
      adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and
      mucosal healing classified as Marsh 0 or I were included. In a randomised double
      blind placebo-controlled pilot study, patients consumed toast (approximately 7
      g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with
      adherence of the usual GFD, 14 patients were randomised to gluten intake with
      either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline
      included complaints, quality-of-life, serum antibodies, immunophenotyping of T
      cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life
      questionnaires were collected during and after the safety, washout and efficacy
      phase. Duodenal biopsies were collected after the safety phase and after the
      efficacy phase. A change in histological evaluation according to the modified
      Marsh classification was the primary endpoint. RESULTS: In total, 16 adults were
      enrolled in the study. No serious adverse events occurred during the trial and no
      patients withdrew during the trial. The mean score for the gastrointestinal
      subcategory of the celiac disease quality (CDQ) was relatively high throughout
      the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the
      CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did
      not significantly deteriorate and moreover no differences between the groups were
      observed. During the efficacy phase, neither the placebo nor the AN-PEP group
      developed significant antibody titers. The IgA-EM concentrations remained
      negative in both groups. Two patients were excluded from entering the efficacy
      phase as their mucosa showed an increase of two Marsh steps after the safety
      phase, yet with undetectable serum antibodies, while 14 patients were considered
      histologically stable on gluten with AN-PEP. Also after the efficacy phase, no
      significant deterioration was observed regarding immunohistological and flow
      cytometric evaluation in the group consuming placebo compared to the group
      receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of
      gluten compared to baseline in four out of seven patients on placebo. In the
      seven patients receiving AN-PEP, one patient showed increased and one showed
      decreased IgA-tTG deposits. CONCLUSION: AN-PEP appears to be well tolerated.
      However, the primary endpoint was not met due to lack of clinical deterioration
      upon placebo, impeding an effect of AN-PEP.

PMID- 24124329
TI  - Laparoscopic management of totally intra-thoracic stomach with chronic volvulus.
AB  - AIM: To evaluate the outcomes of patients who underwent laparoscopic repair of
      intra-thoracic gastric volvulus (IGV) and to assess the preoperative work-up.
      METHODS: A retrospective review of a prospectively collected database of patient
      medical records identified 14 patients who underwent a laparoscopic repair of
      IGV. The procedure included reduction of the stomach into the abdomen, total sac
      excision, reinforced hiatoplasty with mesh and construction of a partial
      fundoplication. All perioperative data, operative details and complications were
      recorded. All patients had at least 6 mo of follow-up. RESULTS: There were 4 male
      and 10 female patients. The mean age and the mean body mass index were 66 years
      and 28.7 kg/m(2), respectively. All patients presented with epigastric discomfort
      and early satiety. There was no mortality, and none of the cases were converted
      to an open procedure. The mean operative time was 235 min, and the mean length of
      hospitalization was 2 d. There were no intraoperative complications. Four minor
      complications occurred in 3 patients including pleural effusion, subcutaneous
      emphysema, dysphagia and delayed gastric emptying. All minor complications
      resolved spontaneously without any intervention. During the mean follow-up of 29
      mo, one patient had a radiological wrap herniation without volvulus. She remains
      symptom free with daily medication. CONCLUSION: The laparoscopic management of
      IGV is a safe but technically demanding procedure. The best outcomes can be
      achieved in centers with extensive experience in minimally invasive esophageal
      surgery.

PMID- 24124330
TI  - Role of Salmonella enterica exposure in Chilean Crohn's disease patients.
AB  - AIM: To study the association between exposure to Salmonella enterica (SE) and
      Crohn's disease (CD) and its clinical implications in Chilean patients. METHODS:
      Ninety-four unrelated Chilean CD patients from CAREI (Active Cohort Registry of
      Inflammatory Bowel Disease) presenting to a single inflammatory bowel disease
      (IBD) unit of a University Hospital were prospectively included in this study. A
      complete clinical evaluation, including smoking history, was performed at the
      initial visit, and all the important data of clinical evolution of CD were
      obtained. Blood samples from these CD patients and 88 healthy sex- and age
      matched control subjects were analyzed for exposure to SE and for their
      NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide
      antibodies [immunoglobulin-G type (IgG)] and polymerase chain reaction (PCR),
      respectively. We also evaluated exposure to SE in 90 sex- and age-matched
      patients without CD, but with known smoking status (30 smokers, 30 non-smokers,
      and 30 former smokers). RESULTS: CD patients comprised 54 females and 40 males,
      aged 35.5 +/- 15.2 years at diagnosis with a mean follow-up of 9.0 +/- 6.8 years.
      CD was inflammatory in 59 patients (62.7%), stricturing in 24 (25.5%) and
      penetrating in 15 (15.5%). Thirty cases (31.9%) had lesions in the ileum, 29
      (30.8%) had ileocolonic lesions, 32 (34.0%) had colonic lesions and 23 (24.4%)
      had perianal disease. Sixteen CD patients (17%) were exposed to SE compared to 15
      (17%) of 88 healthy control subjects (P = 0.8). Thirty-one CD patients (32.9%)
      were smokers, and 7 (7.4%) were former smokers at diagnosis. In the group exposed
      to SE, 10 of 16 patients (62.5%) were active smokers compared to 21 of 78
      patients (26.9%) in the unexposed group (P = 0.01). On the other hand, 10 of 31
      smoking patients (32%) were exposed to SE compared to 5 of 56 nonsmoking patients
      (9%), and one of the seven former smokers (14%) (P = 0.01). In the group of 90
      patients without CD, but whose smoking status was known, there was no difference
      in exposure to SE [3 of 30 smokers (10%), 5 of 30 non-smokers (16%), and 5 of 30
      former smokers (16%); P = 0.6]. There were no differences in disease severity
      between CD patients with and those without anti-SE IgG antibodies, estimated as
      the appearance of stricturing [2 (12.5%) vs 22 (28.2%); P = 0.2] or penetrating
      lesions [2 (12.5%) vs 13 (16.6%); P = 1.0]; or the need for immunosuppressants
      [11 (68.7%) vs 55 (70.5%); P = 1.0], anti-tumor necrosis factor therapy [1 (6.2%)
      vs 7 (8.9%); P = 1.0], hospitalization [13 (81.2%) vs 58 (74.3%); P = 0.7], or
      surgery [3 (18.7%) vs 12 (15.3%); P = 0.3), respectively]. No other factors were
      associated with SE, including NOD2/CARD15 gene status. Seventeen CD patients
      (18%) had at least one mutation of the NOD2/CARD15 gene. CONCLUSION: Our study
      found no association between exposure to SE and CD. We observed a positive
      correlation between SE exposure and cigarette smoking in Chilean patients with
      CD, but not with disease severity.

PMID- 24124331
TI  - Modulation of individual components of gastric motor response to duodenal
      glucose.
AB  - AIM: To evaluate individual components of the antro-pyloro-duodenal (APD) motor
      response to graded small intestinal glucose infusions in healthy humans. METHODS:
      APD manometry was performed in 15 healthy subjects (12 male; 40 +/- 5 years, body
      mass index 26.5 +/- 1.6 kg/m(2)) during four 20-min intraduodenal infusions of
      glucose at 0, 0.5, 1.0 and 1.5 kcal/min, in a randomised double-blinded fashion.
      Glucose solutions were infused at a rate of 1 mL/min and separated by 40-min
      "wash-out" period. Data are mean +/- SE. Inferential analyses are repeated
      measure analysis of variance with Bonferroni post-hoc testing. RESULTS: At 0
      kcal/min frequency of pressure waves were: antrum (7.5 +/- 1.8 waves/20 min) and
      isolated pyloric pressure waves (IPPWs) (8.0 +/- 2.3 waves/20 min) with pyloric
      tone (0.0 +/- 0.9 mmHg). Intraduodenal glucose infusion acutely increased IPPW
      frequency (P < 0.001) and pyloric tone (P = 0.015), and decreased antral wave
      frequency (P = 0.007) in a dose-dependent fashion. A threshold for stimulation
      was observed at 1.0 kcal/min for pyloric phasic pressure waves (P = 0.002) and
      1.5 kcal/min for pyloric tone and antral contractility. CONCLUSION: There is
      hierarchy for the activation of gastrointestinal motor responses to duodenal
      glucose infusion. An increase in IPPWs is the first response observed.

PMID- 24124332
TI  - ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a
      Korean population.
AB  - AIM: To evaluate the association between the genetic polymorphisms and haplotypes
      of the ITGA1 gene and the risk of gastric cancer. METHODS: The study subjects
      were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15
      single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric
      cancer and these SNPs and haplotypes were analyzed with multivariate conditional
      logistic regression models. Multiple testing corrections were carried out
      following methodology for controlling the false discovery rate. Gene-based
      association tests were performed using the versatile gene-based association study
      (VEGAS) method. RESULTS: In the codominant model, the ORs for SNPs rs2432143
      (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were
      statistically significant. In the dominant model, polymorphisms of rs1862610 and
      rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI:
      1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive
      model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150
      2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective
      factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI:
      0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884).
      The ITGA1 gene showed a significant gene-based association with gastric cancer in
      the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2
      was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867
      might be related to the severity of gastric epithelial injury due to inflammation
      and, thus, to the risk of developing gastric cancer. CONCLUSION: ITGA1 gene SNPs
      rs1862610, rs24321 43, and rs2447867 and the ITGA1 haplotype block that includes
      SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

PMID- 24124333
TI  - Non-invasive assessment of choledocholithiasis in patients with gallstones and
      abnormal liver function.
AB  - AIM: To find a non-invasive strategy for detecting choledocholithiasis before
      cholecystectomy, with an acceptable negative rate of endoscopic retrograde
      cholangiopancreatography. METHODS: All patients with symptomatic gallstones were
      included in the study. Patients with abnormal liver functions and common bile
      duct abnormalities on ultrasound were referred for endoscopic retrograde
      cholangiopancreatography. Patients with normal ultrasound were referred to
      magnetic resonance cholangiopancreatography. All those who had a negative
      magnetic resonance or endoscopic retrograde cholangiopancreatography underwent
      laparoscopic cholecystectomy with intraoperative cholangiography. RESULTS:
      Seventy-eight point five percent of patients had laparoscopic cholecystectomy
      directly with no further investigations. Twenty-one point five percent had
      abnormal liver function tests, of which 52.8% had normal ultrasound results. This
      strategy avoided unnecessary magnetic resonance cholangiopancreatography in 47.2%
      of patients with abnormal liver function tests with a negative endoscopic
      retrograde cholangiopancreatography rate of 10%. It also avoided un-necessary
      endoscopic retrograde cholangiopancreatography in 35.2% of patients with abnormal
      liver function. CONCLUSION: This strategy reduces the cost of the routine use of
      magnetic resonance cholangiopancreatography, in the diagnosis and treatment of
      common bile duct stones before laparoscopic cholecystectomy.

PMID- 24124334
TI  - Erosive esophagitis associated with metabolic syndrome, impaired liver function,
      and dyslipidemia.
AB  - AIM: To investigate whether erosive esophagitis is correlated with metabolic
      syndrome and its components, abnormal liver function, and lipoprotein profiles.
      METHODS: We conducted a cross-sectional, case control study of subjects who
      underwent upper endoscopy during a health examination at the Health Management
      and Evaluation Center of a tertiary medical care facility located in Southern
      Taiwan. Metabolic syndrome components, body mass index (BMI), liver function,
      dyslipidemia, and cardiovascular risk factors, as defined by the ratio of total
      cholesterol to high-density lipoprotein cholesterol (HDL-C), and the ratio of low
      density lipoprotein cholesterol to HDL-C were compared between individuals with
      and without erosive esophagitis. Risk factors for erosive esophagitis were
      evaluated by multivariate logistic regression. RESULTS: Erosive esophagitis was
      diagnosed in 507 of 5015 subjects who were individually age and sex matched to
      507 esophagitis-free control subjects. In patients with erosive esophagitis, BMI,
      waist circumference, blood pressure, fasting plasma glucose, triglyceride levels,
      aspartate aminotransferase, alanine aminotransferase, the ratio of total
      cholesterol to HDL-C, and the ratio of low-density lipoprotein cholesterol to HDL
      C were significantly higher and HDL-C was significantly lower compared to
      patients without erosive esophagitis (all P < 0.05). In a multivariate analysis,
      central obesity (OR = 1.38; 95%CI: 1.0-1.86), hypertension (OR = 1.35; 95%CI:
      1.04-1.76), hypertriglyceridemia (OR = 1.34; 95%CI: 1.02-1.76), cardiovascular
      risk factors as defined by a ratio of total cholesterol to HDL-C > 5 (OR = 1.45;
      95%CI: 1.06-1.97), and aspartate aminotransferase (OR = 1.59; 95%CI: 1.08-2.34)
      were significantly associated with erosive esophagitis. CONCLUSION: Metabolic
      syndrome, impaired liver function, and a higher ratio of total cholesterol to HDL
      C were associated with erosive esophagitis.

PMID- 24124335
TI  - Effect of early enteral combined with parenteral nutrition in patients undergoing
      pancreaticoduodenectomy.
AB  - AIM: To investigate the effect of early enteral nutrition (EEN) combined with
      parenteral nutritional support in patients undergoing pancreaticoduodenectomy
      (PD). METHODS: From January 2006, all patients were given EEN combined with
      parenteral nutrition (PN) (EEN/PN group, n = 107), while patients prior to this
      date were given total parenteral nutrition (TPN) (TPN group, n = 67). Venous
      blood samples were obtained for a nutrition-associated assessment and liver
      function tests on the day before surgery and 6 d after surgery. The assessment of
      clinical outcome was based on postoperative complications. Follow-up for
      infectious and noninfectious complications was carried out for 30 d after
      hospital discharge. Readmission within 30 d after discharge was also recorded.
      RESULTS: Compared with the TPN group, a significant decrease in prealbumin (PAB)
      (P = 0.023) was seen in the EEN/PN group. Total bilirubin (TB), direct bilirubin
      (DB) and lactate dehydrogenase (LDH) were significantly decreased on day 6 in the
      EEN/PN group (P = 0.006, 0.004 and 0.032, respectively). The rate of grade I
      complications, grade II complications and the length of postoperative hospital
      stay in the EEN/PN group were significantly decreased (P = 0.036, 0.028 and
      0.021, respectively), and no hospital mortality was observed in our study.
      Compared with the TPN group (58.2%), the rate of infectious complications in the
      EEN/PN group (39.3%) was significantly decreased (P = 0.042). Eleven cases of
      delayed gastric emptying were noted in the TPN group, and 6 cases in the EEN/PN
      group. The rate of delayed gastric emptying and hyperglycemia was significantly
      reduced in the EEN/PN group (P = 0.031 and P = 0.040, respectively). CONCLUSION:
      Early enteral combined with PN can greatly improve liver function, reduce
      infectious complications and delayed gastric emptying, and shorten postoperative
      hospital stay in patients undergoing PD.

PMID- 24124336
TI  - Association between UCP3 gene polymorphisms and nonalcoholic fatty liver disease
      in Chinese children.
AB  - AIM: To confirm the hypothesis that polymorphisms of the uncoupling protein 3
      (UCP3) gene are associated with the occurrence of nonalcoholic fatty liver
      disease (NAFLD). METHODS: A total of 250 NAFLD patients (147 males and 103
      females) and 200 healthy individuals who served as controls (control, 109 males
      and 91 females), aged between 6 and 16 years were enrolled in this study. The
      four non-synonymous single nucleotide polymorphisms (SNPs) in the UCP3 gene
      polymorphisms of rs1726745, rs3781907, rs11235972 and rs1800849, were genotyped
      using MassArray. Body mass index (BMI), waist and hip circumference, blood
      pressure (BP), fasting blood glucose (FBG), insulin and lipid profiles were
      measured and B-ultrasound examination was performed in all subjects. RESULTS:
      NAFLD patients showed risk factors for metabolic syndrome: elevated BMI, waist-to
      hip ratio, BP, FBG, homeostasis model assessment-estimated insulin resistance,
      total triglyceride, total cholesterol and low-density lipoprotein-cholesterol,
      while decreased high-density lipoprotein-cholesterol level compared with the
      control group. The GG genotype distributions of rs11235972 in the NAFLD group
      differed significantly from that in the control group. We found that waist
      circumference between CC (58.76 +/- 6.45 cm) and CT+TT (57.00 +/- 5.59 cm), and
      hip circumference between CC (71.28 +/- 7.84 cm) and CT+TT genotypes (69.06 +/-
      7.75 cm) were significantly different with and without rs1800849 variation (P <
      0.05). CONCLUSION: A higher prevalence of rs11235972 GG genotype was observed in
      the NAFLD group compared with the control group. No differences were observed for
      the other SNPs. However, there was a significant difference in body height in
      addition to waist and hip circumference between the CC (mutant type group) and
      CT+TT group with and without rs1800849 variation.

PMID- 24124337
TI  - Influence of chronic HBV infection on superimposed acute hepatitis E.
AB  - AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection
      [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on
      superimposed acute hepatitis E. METHODS: A total of 294 patients were recruited
      from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun
      Yat-sen University, from January 2003 to January 2012. The patients were
      classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with
      chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and
      an HEV group (a group with acute hepatitis E, n = 176). We retrospectively
      analyzed and compared the clinical features of the two groups. Statistical
      analyses were performed using the chi(2) test or Fisher's exact test for
      categorical variables and the Student's t test for continuous variables. A P
      value < 0.05 was considered statistically significant. RESULTS: The peak values
      of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease
      scores were significantly higher in the HBV + HEV group. More patients in the HBV
      + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver
      failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV
      group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of
      the HBV + HEV group showed that there were no significant differences in
      complication occurrence, liver failure incidence, or mortality between patients
      with different HBeAg and HBV DNA statuses. However, in patients with underlying
      cirrhosis, complication occurrence and liver failure incidence significantly
      increased. In total, 12.7% of the patients in the HBV + HEV group received anti
      HBV treatment, but this therapy failed to reduce mortality in patients who
      developed liver failure. CONCLUSION: The presence of underlying cirrhosis in
      chronic HBV infection results in more severe clinical outcomes with superimposed
      acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver
      failure caused by HBV-HEV superinfection.

PMID- 24124338
TI  - A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in
      Chinese patients with metastatic esophageal squamous cell carcinoma.
AB  - AIM: To evaluate the efficacy and safety of paclitaxel-nedaplatin combination as
      a front-line regimen in Chinese patients with metastatic esophageal squamous cell
      carcinoma (ESCC). METHODS: A two-center, open-label, single-arm phase II study
      was designed. Thirty-nine patients were enrolled and included in the intention-to
      treat analysis of efficacy and adverse events. Patients received 175 mg/m2 of
      paclitaxel over a 3 h infusion on 1 d, followed by nedaplatin 80 mg/m2 in a 1 h
      infusion on 2 d every 3 wk until the documented disease progression, unacceptable
      toxicity or patient's refusal. RESULTS: Of the 36 patients assessable for
      efficacy, there were 2 patients (5.1%) with complete response and 16 patients
      (41.0%) with partial response, giving an overall response rate of 46.1%. The
      median progression-free survival and median overall survival for all patients
      were 7.1 mo (95%CI: 4.6-9.7) and 12.4 mo (95%CI: 9.5-15.3), respectively.
      Toxicities were moderate and manageable. Grade 3/4 toxicities included
      neutropenia (15.4%), nausea (10.3%), anemia (7.7%), thrombocytopenia (5.1%),
      vomiting (5.1%) and neutropenia fever (2.6%). CONCLUSION: The combination of
      paclitaxel and nedaplatin is active and well tolerated as a first-line therapy
      for patients with metastatic ESCC.

PMID- 24124339
TI  - Association between vitamin D and hepatitis C virus infection: a meta-analysis.
AB  - AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and
      sustained virological response (SVR) in hepatitis C virus (HCV) infected
      individuals. METHODS: Relevant studies were identified by systematically
      searching MEDLINE databases up to March 2012 and abstracts of the European and
      American Congress of Hepatology conducted in 2011. Studies must provide
      information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth
      referred to as 25(OH)D] in sera samples from HCV infected individuals. The
      inclusion criteria were: clinical studies that included HCV infected patients
      aged older than 18 years regardless of HCV genotype or ethnic group; provided
      information on SVR rates; and were reported in the English language as full
      papers. Due to the heterogeneity of studies in categorizing serum vitamin D
      levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was
      assessed using I2 statistics. The summary odds ratios with their corresponding
      95%CI were calculated based on a random-effects model. RESULTS: Overall, 11
      studies (8 observational and 3 interventional) involving 1575 individuals were
      included and 1117 HCV infected individuals (71%) showed low vitamin D levels.
      Most of the studies included mono-infected HCV individuals with the mean age
      ranging from 38 to 56 years. Four studies were conducted in human
      immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement,
      most of the studies employed radioimmunoassays (n = 5) followed by
      chemiluminescence (n = 4) and just one study employed high performance/pressure
      liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL
      in the studies selected, and most of the HCV infected individuals had genotype 1
      (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to
      HCV treatment, most of the studies (n = 8) included HCV individuals without
      previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were
      observed in HCV individuals with vitamin D levels above 30 ng/mL (OR = 1.57;
      95%CI: 1.12-2.2) and those supplemented with vitamin D (OR = 4.59; 95%CI: 1.67
      12.63) regardless of genotype. CONCLUSION: Our results demonstrated high
      prevalence of vitamin D deficiency and high SVR in individuals with higher serum
      vitamin D levels or receiving vitamin D supplementation.

PMID- 24124340
TI  - Laparoscopic cholecystectomy for a left-sided gallbladder.
AB  - Cholecystectomy is a common procedure. Abnormalities in the anatomy of the
      biliary system are common but an abnormal location of the gallbladder is much
      rarer. Despite frequent pre-operative imaging, the aberrant location of the
      gallbladder is commonly discovered at surgery. This article presents a case of a
      patient with the gallbladder located to the left of the falciform ligament in the
      absence of situs inversus totalis that presented with right upper quadrant pain.
      A laparoscopic cholecystectomy was performed and it was noted that the cystic
      duct originated from the right side. The presence of a left sided gall bladder is
      often associated with various biliary, portal venous and other anomalies that
      might lead to intra-operative injuries. The spectrum of unusual positions and
      anatomical gallbladder abnormalities is reviewed in order to facilitate elective
      and emergent cholecystectomy as well as other hepatobiliary procedures. With
      proper identification of the anatomy, minimally invasive approaches are still
      considered safe. 

PMID- 24124341
TI  - Totally laparoscopic left hepatectomy using the Torsional Ultrasonic Scalpel.
AB  - Minimal invasive techniques have allowed for major surgical advances. We report
      our initial experience of performing total laparoscopic left hepatectomy
      (segments II-IV) with the Lotus (laparoscopic operation by torsional ultrasound)
      Ultrasonic Scalpel. The perioperative and postoperative courses of the young
      female patient were uneventful and she is in a good general condition without
      complaints 18 mo after surgery. To the best of our knowledge, this is the first
      total laparoscopic hemihepatectomy to be performed in Greece, as well as the
      first laparoscopic liver resection using Lotus shears. 

PMID- 24124342
TI  - Crohn's disease and Takayasu's arteritis: an uncommon association.
AB  - Takayasu's arteritis (TA) and Crohn's disease (CD) are two rare autoimmune
      disorders; however some reports describe the presence of both diseases in the
      same patient. This finding has suggested the possibility that both diseases could
      share some common etiologic origin. We describe a case of a 13-year-old male
      affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and
      elevation of inflammatory markers. Clinical and histological features from
      colonic specimens were consistent with CD. Treatment with steroids and
      azathioprine was started, however disease flared every time steroids were
      tapered. One year later, while still on treatment, he came back to our attention
      for dyspnea at rest and at night, tiredness and weakness. At physical examination
      a diastolic heart murmur was found as well as a left carotid artery bruit. A
      transthoracic echocardiography showed mild aortic valve insufficiency, left
      ventricular hypertrophy and a dilated ascending aorta with same findings at the
      aortic arch. A computed tomography scan showed abdominal aorta thickening,
      dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA
      associated with CD was diagnosed and medical treatment with cyclophosphamide,
      steroids and aminosalicylic acid was started, with good clinical response at 6 mo
      follow-up. We discuss the presence of possible common causes for the two diseases
      and the importance of differential diagnosis in those patients characterized for
      intractable disease. 

PMID- 24124343
TI  - Difficult polypectomy-giant hypopharyngeal polyp: case report and literature
      review.
AB  - Giant esophageal and hypopharyngeal polyps are benign tumors rarely encountered
      in clinical practice. In most cases, they are completely asymptomatic; however,
      despite the rarity of these tumors, interest in giant esophageal polyps derives
      from their degree of growth (characterized by slow growth into the esophageal
      lumen) and their mobility. In fact, if regurgitation occurs, they can ascend into
      the oral cavity and be aspirated into the airways, with potentially lethal
      consequences. The removal of these giant polyps is recommended. An adequate
      preoperative evaluation to identify the correct origin of the stalk is mandatory
      for a successful endoscopic or surgical treatment. A 60-year-old man was admitted
      to our hospital for anemia. The patient underwent gastroscopy, contrast computed
      tomography and endoscopic ultrasound. At the conclusion of the procedure, during
      the extraction of the echoendoscope, the patient began retching and regurgitated
      the polyp, without experiencing respiratory distress. The patient underwent a
      left cervicotomy and polyp dissection via a pharyngotomy. 

PMID- 24124344
TI  - Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.
AB  - We report the case of a 17-year-old male admitted to our academic hospital with
      massive rectal bleeding. Since childhood he had reported recurrent
      gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years
      previously. An emergency abdominal computed tomography scan, gastroscopy and
      colonoscopy, performed after hemodynamic stabilization, were considered normal.
      High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and
      bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h
      after each cessation of PPI which led to a hemostatic laparotomy after negative
      gastroscopy and small bowel capsule endoscopy. This showed long tubular
      duplication of the right colon, with fresh blood in the duplicated colon. Obscure
      lower gastrointestinal bleeding is a difficult medical situation and potentially
      life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic
      duplication explains the partial efficacy of PPI therapy. Obscure
      gastrointestinal bleeding responding to empiric anti-acid therapy should probably
      evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's
      diverticulum or gastrointestinal duplication, and gastroenterologists should be
      aware of this potential medical situation. 

PMID- 24124345
TI  - Capsule-odometer: a concept to improve accurate lesion localisation.
AB  - In order to improve lesion localisation in small-bowel capsule endoscopy, a
      modified capsule design has been proposed incorporating localisation and - in
      theory - stabilization capabilities. The proposed design consists of a capsule
      fitted with protruding wheels attached to a spring-mechanism. This would act as a
      miniature odometer, leading to more accurate lesion localization information in
      relation to the onset of the investigation (spring expansion e.g., pyloric
      opening). Furthermore, this capsule could allow stabilization of the recorded
      video as any erratic, non-forward movement through the gut is minimised. Three
      dimensional (3-D) printing technology was used to build a capsule prototype.
      Thereafter, miniature wheels were also 3-D printed and mounted on a spring which
      was attached to conventional capsule endoscopes for the purpose of this proof-of
      concept experiment. In vitro and ex vivo experiments with porcine small-bowel are
      presented herein. Further experiments have been scheduled. 

PMID- 24124346
TI  - The evolving role of physiotherapists in pre-employment screening for workplace
      injury prevention: are functional capacity evaluations the answer?
AB  - BACKGROUND: Musculoskeletal injuries account for the largest proportion of
      workplace injuries. In an attempt to predict, and subsequently manage, the risk
      of sprains and strains in the workplace, employers are turning to pre-employment
      screening. Functional capacity evaluations (FCEs) are increasing in popularity as
      a tool for pre-employment screening despite limited published evidence for their
      validity in healthy working populations. OBJECTIVES: This narrative review will
      present an overview of the state of the evidence for pre-employment functional
      testing, propose a framework for decision-making to determine the suitability of
      assessment tools, and discuss the role and potential ethical challenges for
      physiotherapists conducting pre-employment functional testing. MAJOR FINDINGS:
      Much of the evidence surrounding the validity of functional testing is in the
      context of the injured worker and prediction of return to work. In healthy
      populations, FCE components, such as aerobic fitness and manual handling
      activities, have demonstrated predictability of workplace injury in a small
      number of studies. This predictability improves when workers' performance is
      compared with the job demands. This job-specific approach is also required to
      meet anti-discrimination requirements. There are a number of practical
      limitations to functional testing, although these are not limited to the pre
      employment domain. Physiotherapists need to have a clear understanding of the
      legal requirements and potential ethical challenges that they may face when
      conducting pre-employment functional assessments (PEFAs). CONCLUSIONS: Further
      research is needed into the efficacy of pre-employment testing for workplace
      injury prevention. Physiotherapists and PEFAs are just one part of a holistic
      approach to workplace injury prevention.

PMID- 24124347
TI  - How Young is "Too Young" to Start Training?

PMID- 24124348
TI  - Visual performance after the implantation of a new trifocal intraocular lens.
AB  - PURPOSE: To evaluate the subjective and objective visual results after the
      implantation of a new trifocal diffractive intraocular lens. METHODS: A NEW
      TRIFOCAL DIFFRACTIVE INTRAOCULAR LENS WAS DESIGNED COMBINING TWO SUPERIMPOSED
      DIFFRACTIVE PROFILES: one with +1.75 diopters (D) addition for intermediate
      vision and the other with +3.50 D addition for near vision. Fifty eyes of 25
      patients that were operated on by one surgeon are included in this study. The
      uncorrected and best distance-corrected monocular and binocular, near,
      intermediate, and distance visual acuities, contrast sensitivity, and defocus
      curves were measured 6 months postoperatively. In addition to the standard
      clinical follow-up, a questionnaire evaluating individual satisfaction and
      quality of life was submitted to the patients. RESULTS: The mean age of patients
      at the time of surgery was 70 +/- 10 years. The mean uncorrected and corrected
      monocular distance visual acuity (VA) were LogMAR 0.06 +/- 0.10 and LogMAR 0.00
      +/- 0.08, respectively. The outcomes for the binocular uncorrected distance
      visual acuity were almost the same (LogMAR -0.04 +/- 0.09). LogMAR -010 +/- 0.15
      and 0.02 +/- 0.06 were measured for the binocular uncorrected intermediate and
      near VA, respectively. The distance-corrected visual acuity was maintained in
      mesopic conditions. The contrast sensitivity was similar to that obtained after
      implantation of a bifocal intraocular lens and did not decrease in mesopic
      conditions. The binocular defocus curve confirms good VA even in the intermediate
      distance range, with a moderate decrease of less than LogMAR 0.2 at -1.5 D, with
      respect to the best distance VA at 0 D defocus. Patient satisfaction was high. No
      discrepancy between the objective and subjective outcomes was evidenced.
      CONCLUSION: The introduction of a third focus in diffractive multifocal
      intraocular lenses improves the intermediate vision with minimal visual
      discomfort for the patient.

PMID- 24124349
TI  - Comparison of surgically induced astigmatism between one-handed and two-handed
      cataract surgery techniques.
AB  - BACKGROUND: The purpose of this study was to compare surgically induced
      astigmatism (SIA) between one-handed and two-handed cataract surgery techniques.
      METHODS: Eighty-eight eyes of 44 patients with no ocular disease other than
      cataract, who underwent cataract surgery by a single surgeon, were selected for
      this study. Cataract surgery was performed by coaxial phacoemulsification and
      intraocular lens implantation via a 2.4 mm transconjunctival single-plane
      sclerocorneal incision at the 12 o'clock position. In each patient, one eye was
      subjected to coaxial phacoemulsification using a one-handed technique while the
      fellow eye was subjected to coaxial phacoemulsification using a two-handed
      technique. For the two-handed technique, a corneal side port was created at the 2
      o'clock position. The appropriate incision meridian was identified by a
      preoperative axis mark. SIA was calculated using the Alpins method. RESULTS: Mean
      SIA was 0.40 +/- 0.28 diopters (D) in the one-handed technique group and 0.39 +/-
      0.25 D in the two-handed technique group. No statistically significant difference
      was found in the mean SIA score. The mean torque value was -0.05 +/- 0.26 D in
      the one-handed technique group and 0.11 +/- 0.37 D in the two-handed technique
      group. Mean torque was significantly lower (P<0.05) in the one-handed technique
      group than in the two-handed technique group. CONCLUSION: The results indicate
      that the corneal side port in two-handed cataract surgery has a rotating effect
      on the axis of astigmatism.

PMID- 24124350
TI  - Ready for OR or not? Human reader supplements Eyesi scoring in cataract surgical
      skills assessment.
AB  - PURPOSE: To compare the internal computer-based scoring with human-based video
      scoring of cataract modules in the Eyesi virtual reality intraocular surgical
      simulator, a comparative case series was conducted at the Department of Clinical
      Sciences - Ophthalmology, Lund University, Skane University Hospital, Malmo,
      Sweden. METHODS: Seven cataract surgeons and 17 medical students performed one
      video-recorded trial with each of the capsulorhexis, hydromaneuvers, and
      phacoemulsification divide-and-conquer modules. For each module, the simulator
      calculated an overall score for the performance ranging from 0 to 100. Two
      experienced masked cataract surgeons analyzed each video using the Objective
      Structured Assessment of Cataract Surgical Skill (OSACSS) for individual models
      and modified Objective Structured Assessment of Surgical Skills (OSATS) for all
      three modules together. The average of the two assessors' scores for each tool
      was used as the video-based performance score. The ability to discriminate
      surgeons from naive individuals using the simulator score and the video score,
      respectively, was compared using receiver operating characteristic (ROC) curves.
      RESULTS: The ROC areas for simulator score did not differ from 0.5 (random) for
      hydromaneuvers and phacoemulsification modules, yielding unacceptably poor
      discrimination. OSACSS video scores all showed good ROC areas significantly
      different from 0.5. The OSACSS video score was also superior compared to the
      simulator score for the phacoemulsification procedure: ROC area 0.945 vs 0.664
      for simulator score (P = 0.010). Corresponding values for capsulorhexis were
      0.887 vs 0.761 (P = 0.056) and for hydromaneuvers 0.817 vs 0.571 (P = 0.052) for
      the video scores and simulator scores, respectively. The ROC area for the
      combined procedure was 0.938 for OSATS video score and 0.799 for simulator score
      (P=0.072). CONCLUSION: Video-based scoring of the phacoemulsification procedure
      was superior to the innate simulator scoring system in distinguishing cataract
      surgical skills. Simulator scoring rendered unacceptably poor discrimination for
      both the hydromaneuvers and the phacoemulsification divide-and-conquer module.
      Our results indicate a potential for improvement in Eyesi internal computer-based
      scoring.

PMID- 24124351
TI  - Predictors and consequences of adherence to the treatment of pediatric patients
      with attention-deficit/hyperactivity disorder in Central Europe and East Asia.
AB  - PURPOSE: To assess baseline predictors and consequences of medication non
      adherence in the treatment of pediatric patients with attention
      deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS
      AND METHODS: Data for this post-hoc analysis were taken from a 1-year
      prospective, observational study that included a total of 1,068 newly-diagnosed
      pediatric patients with ADHD symptoms from Central Europe and East Asia.
      Medication adherence during the week prior to each visit was assessed by treating
      physicians using a 5-point Likert scale, and then dichotomized into either
      adherent or non-adherent. Clinical severity was measured by the Clinical Global
      Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI
      4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child
      Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used
      to assess baseline predictors of overall adherence during follow-up, and the
      impact of time-varying adherence on subsequent outcomes: response (defined as a
      decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five
      dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in
      Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non
      adherent during follow-up. Being from East Asia was found to be a strong
      predictor of non-adherence. In East Asia, a family history of ADHD and parental
      emotional distress were associated with non-adherence, while having no other
      children living at home was associated with non-adherence in Central Europe as
      well as in the overall sample. Non-adherence was associated with poorer response
      and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non
      adherence to medication is common in the treatment of ADHD, particularly in East
      Asia. Non-adherence was associated with poorer response and less improvement in
      clinical severity. A limitation of this study is that medication adherence was
      assessed by the treating clinician using a single item question.

PMID- 24124352
TI  - Psychometric analysis of the Spanish and Catalan versions of the Diabetes Self
      Care inventory-revised version questionnaire.
AB  - BACKGROUND: The purpose of this study was to validate the Spanish and Catalan
      versions of the Diabetes Self-Care Inventory-Revised Version (SCI-R)
      questionnaire to assess the degree of adherence to self-care among adults with
      diabetes. METHODS: We validated the Spanish and Catalan translation from, and
      back translation to, English and cultural adaptation of the SCI-R in type 1
      diabetes patients on multiple insulin doses or continuous subcutaneous insulin
      infusion and in type 2 diabetes patients on oral agents and/or insulin. Internal
      reliability, structural validity, and external validity (correlation with
      glycated hemoglobin) were evaluated. Responsiveness to change was assessed in
      patients 1 year after onset of type 1 diabetes and following a structured
      education program. RESULTS: The SCI-R presented good internal reliability
      Cronbach's alpha: 0.75, test-retest reliability (r = 0.82) and structural
      validity (r > 0.40). The external validity was also good; the SCI-R correlated
      with HbA1c in patients with type 1 diabetes on multiple insulin doses (r = -0.50)
      or continuous subcutaneous insulin infusion (r = -0.66) and in patients with type
      2 diabetes on multiple insulin doses (r = -0.62). However, it was not
      satisfactory in patients on oral agents (r = -0.20) and/or bedtime insulin (r = 
      0.35). Responsiveness to change was analyzed in 54 patients (age 27.3+/-7.4
      years, 26% men, HbA1c 6.8% +/-1.1%); the SCI-R score was 72.3% +/-13.7% and
      correlated negatively with glycated hemoglobin (r = -0.42) and 3 scales of the
      Diabetes Quality of Life questionnaire (lower score indicating better
      perception): Impact (r = -0.37), Social Worry (r = -0.36) and Diabetes Worry (r =
      -0.38), all at P < 0.05. CONCLUSION: The Spanish and Catalan versions of the SCI
      R questionnaire show good psychometric properties and both could be considered as
      useful tools for evaluating self-care behavior in patients with type 1 or type 2
      diabetes. However, there are still some subgroups of patients with type 2
      diabetes in which the validity of this questionnaire needs further evaluation.

PMID- 24124353
TI  - A study to assess the feasibility of undertaking a randomized controlled trial of
      adherence with eye drops in glaucoma patients.
AB  - BACKGROUND: Adherence with therapy could influence the progression of glaucoma
      and ultimately affect the onset of visual impairment in some individuals. This
      feasibility study evaluated the measures to be used for a future randomized
      controlled trial assessing the effects of group-based education on adherence with
      eye drops. METHODS: People diagnosed with glaucoma within the previous 12 months
      attending a regional ophthalmology clinic in the North West of England were
      recruited. A two-session education program delivered one week apart had been
      devised as part of a previous project. A combined adult learning and health needs
      approach to education was taken. Outcomes measured were knowledge of glaucoma,
      self-report of adherence, illness perception, beliefs about medicines, patient
      enablement, and general health (Short Form-12). Adherence was also measured
      objectively using a Medical Events Monitoring System device. RESULTS: Twenty-six
      participants consented to undertake the educational program and 19 produced
      analyzable data. Knowledge of glaucoma, illness perception, beliefs about
      medicine, and patient enablement all showed statistically significant
      improvements after education. Mean adherence with eye drops was maintained above
      85% before and for 3 months after attendance at the educational program. Self
      report exaggerated adherence by at least 10% when compared with the objective
      Medical Events Monitoring System data, and in fact the kappa agreement was zero.
      CONCLUSION: All questionnaires other than the Short Form-12 were considered to be
      valuable measures and use of a Medical Events Monitoring System device was
      considered to be an objective surrogate measure for adherence with eye drops. A
      multicenter, randomized, controlled equivalence trial of group versus
      individualized education using adherence as the primary outcome is the next step.

PMID- 24124354
TI  - Evidence for the long term cost effectiveness of home care reablement programs.
AB  - BACKGROUND: The objectives of this study were to determine whether older
      individuals who participated in a reablement (restorative) program rather than
      immediately receiving conventional home care services had a reduced need for
      ongoing support and lower home care costs over the next 57 months (nearly 5
      years). MATERIALS AND METHODS: Data linkage was used to examine retrospectively
      the service records of older individuals who had received a reablement service
      versus a conventional home care service to ascertain their use of home care
      services over time. RESULTS: Individuals who had received a reablement service
      were less likely to use a personal care service throughout the follow-up period
      or any other type of home care over the next 3 years. This reduced use of home
      care services was associated with median cost savings per person of approximately
      AU $12,500 over nearly 5 years. CONCLUSION: The inclusion of reablement as the
      starting point for individuals referred for home care within Australia's reformed
      aged care system could increase the system's cost effectiveness and ensure that
      all older Australians have the opportunity to maximize their independence as they
      age.

PMID- 24124355
TI  - Safety and efficacy of montelukast as adjunctive therapy for treatment of asthma
      in elderly patients.
AB  - Asthma is a disease of all ages. This assumption has been challenged in the past,
      because of several cultural and scientific biases. A large body of evidence has
      accumulated in recent years to confirm that the prevalence of asthma in the most
      advanced ages is similar to that in younger ages. Asthma in the elderly may show
      similar functional and clinical characteristics to that occurring in young
      adults, although the frequent coexistence of comorbid conditions in older
      patients, together with age-associated changes in the human lung, may lead to
      more severe forms of the disease. Management of asthma in the elderly follows
      specific guidelines that apply to all ages, although most behaviors are pure
      extrapolation of what has been tested in young ages. In fact, age has always
      represented an exclusion criterion for eligibility to clinical trials. This
      review focuses specifically on the safety and efficacy of leukotriene modifiers,
      which represent a valid option in the treatment of allergic asthma, both as an
      alternative to first-line drugs and as add-on treatment to inhaled
      corticosteroids. Available studies specifically addressing the role of
      montelukast in the elderly are scarce; however, leukotriene modifiers have been
      demonstrated to be safe in this age group, even though cases of acute hepatitis
      and occurrence of Churg-Strauss syndrome have been described in elderly patients;
      whether this is associated with age is to be confirmed. Furthermore, leukotriene
      modifiers provide additional benefit when added to regular maintenance therapy,
      not differently from young asthmatics. In elderly patients, the simpler route of
      administration of leukotriene modifiers, compared with the inhaled agents, could
      represent a more effective strategy in improving the outcomes of asthma therapy,
      given that unintentional nonadherence with inhalation therapy represents a
      complex problem that may lead to significant impairment of asthma symptom
      control. 

PMID- 24124356
TI  - Is cochlear implantation a good treatment method for profoundly deafened elderly?
AB  - PURPOSE: To assess the benefits of cochlear implantation in the elderly. PATIENTS
      AND METHODS: A retrospective analysis of 31 postlingually deafened elderly (>=60
      years of age) with unilateral cochlear implants was conducted. Audiological
      testing included preoperative and postoperative pure-tone audiometry and a
      monosyllabic word recognition test presented from recorded material in free
      field. Speech perception tests included Ling's six sound test (sound detection,
      discrimination, and identification), syllable discrimination, and monosyllabic
      and multisyllabic word recognition (open set) without lip-reading. Everyday life
      benefits from cochlear implantation were also evaluated. RESULTS: The mean age at
      the time of cochlear implantation was 72.4 years old. The mean postimplantation
      follow-up time was 2.34 years. All patients significantly improved their
      audiological and speech understanding performances. The preoperative mean pure
      tone average threshold for 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was 110.17 dB
      HL. Before cochlear implantation, all patients scored 0% on the monosyllabic word
      recognition test in free field at 70 dB SPL intensity level. The postoperative
      pure-tone average was 37.14 dB HL (the best mean threshold was 17.50 dB HL, the
      worst was 58.75 dB HL). After the surgery, mean monosyllabic word recognition
      reached 47.25%. Speech perception tests showed statistically significant
      improvement in speech recognition. CONCLUSION: The results of this study showed
      that cochlear implantation is indeed a successful treatment for improving speech
      recognition and offers a great help in everyday life to deafened elderly
      patients. Therefore, they can be good candidates for cochlear implantation and
      their age alone should not be a relevant or excluding factor when choosing
      candidates for cochlear implantation.

PMID- 24124357
TI  - Prevalence of vitamin D deficiency during the summer and its relationship with
      sun exposure and skin phototype in elderly men living in the tropics.
AB  - OBJECTIVE: The aim of the study reported here was to determine the prevalence of
      vitamin D deficiency among elderly men and its association with sun exposure and
      skin phototypes. SUBJECTS AND METHODS: This was an analytical cross-sectional
      study, which involved 284 men aged 60 years or over, randomly recruited from a
      basic care unit in the city of Recife (Brazil). MEASUREMENTS: Serum levels of 25
      hydroxyvitamin D (25(OH)D), sun index, and skin phototypes were evaluated.
      RESULTS: The prevalence of vitamin D deficiency was 31.5% and 66.7% when cut
      points of less than 20 and 30 ng/mL, respectively, were used. Mean serum 25(OH)D
      was 27.86 +/- 13.52 standard deviation (SD) ng/mL. There was no difference (P =
      0.113) in 25(OH) D (23.98 +/- 14.66 SD vs 29.88 +/- 13.78 SD) between individuals
      in the lowest quartile (Q) of the sun index (Q1: 1.96) compared with those in the
      highest (Q4: 7.86). When considering a cutoff of 20 ng/mL, the sun index was
      different in the two groups (P = 0.006), but there was no difference when cutoffs
      of 25 and 30 ng/mL were used. After adjustment, sun index and body mass index
      were associated positively and negatively, respectively with serum 25(OH)D
      independently. Most subjects (66.7%) had Fitzpatrick's skin phototypes IV, V, and
      VI. Low calcium intake was observed in 72%. There was no difference in serum
      25(OH)D levels between patients with low intake and those with intermediate and
      high intakes. Only 2.5% were taking a vitamin supplement. CONCLUSION: We found a
      high prevalence of vitamin D deficiency among elderly men despite their high sun
      exposure during the summer months.

PMID- 24124358
TI  - A study to assess COPD Symptom-based Management and to Optimise treatment
      Strategy in Japan (COSMOS-J) based on GOLD 2011.
AB  - BACKGROUND AND OBJECTIVE: The Global initiative for chronic Obstructive Lung
      Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease
      (COPD) assessment framework focused on symptoms and on exacerbation risk. This
      study will evaluate a symptom and exacerbation risk-based treatment strategy
      based on GOLD in a real-world setting in Japan. Optimal management of COPD will
      be determined by assessing symptoms using the COPD Assessment Test (CAT) and by
      assessing the frequency of exacerbations. METHODS: This study (ClinicalTrials.gov
      identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind,
      double-dummy, parallel-group study. It aims to recruit 400 patients with moderate
      to-severe COPD. Patients will be randomized to receive treatment with either
      salmeterol/fluticasone propionate (SFC) 50/250 MUg twice daily or with tiotropium
      bromide 18 MUg once daily. Optimal management of patients will be assessed at
      four-weekly intervals and, if patients remain symptomatic, as measured using the
      CAT, or experience an exacerbation, they have the option to step up to treatment
      with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy).
      The primary endpoint of the study will be the proportion of patients who are able
      to remain on the randomized therapy. RESULTS: No data are available. This paper
      summarizes the methodology of the study in advance of the study starting.
      CONCLUSION: The results of this study will help physicians to understand whether
      TRIPLE therapy is more effective than either treatment strategy alone in
      controlling symptoms and exacerbations in patients with moderate-to-severe COPD.
      It will also help physicians to understand the GOLD recommendation work in Japan.

PMID- 24124359
TI  - Impact of active and passive smoking as risk factors for asthma and COPD in women
      presenting to primary care in Syria: first report by the WHO-GARD survey group.
AB  - BACKGROUND: The burden of chronic respiratory disease (CRD) is alarming.
      International studies suggest that women with CRD are undersurveyed and
      underdiagnosed by physicians worldwide. It is unclear what the prevalence of CRD
      is in the general population of Syria, particularly among women, since there has
      never been a survey on CRD in this nation. The purpose of this study was to
      investigate the impact of different patterns of smoking on CRD in women.
      MATERIALS AND METHODS: We extracted data on smoking patterns and outcome in women
      from the Global Alliance Against Chronic Respiratory Diseases survey. Using
      spirometric measurements before and after the use of inhaled bronchodilators, we
      tracked the frequency of CRD in females active and passive narghile or cigarette
      smokers presenting to primary care. We administered the questionnaire to 788
      randomly selected females seen during 1 week in the fiscal year 2009-2010 in 22
      primary care centers in six different regions of Syria. Inclusion criteria were
      age >6 years, presenting for any medical complaint. In this cross-sectional
      study, three groups of female subjects were evaluated: active smokers of
      cigarettes, active smokers of narghiles, and passive smokers of either cigarettes
      or narghiles. These three groups were compared to a control group of female
      subjects not exposed to active or passive smoking. RESULTS: Exposure to active
      cigarette smoke but not narghile smoke was associated with doctor-diagnosed
      chronic obstructive pulmonary disease (COPD). However, neither cigarette nor
      narghile active smoking was associated with increased incidence of
      spirometrically diagnosed COPD. Paradoxically, exposure to passive smoking of
      either cigarettes or narghiles resulted in association with airway obstruction,
      defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity
      (FVC) < 70% according to the Global initiative for chronic Obstructive Lung
      Disease criteria; association with FEV1 < 80% predicted, evidencing moderate to
      severe GOLD spirometric grade, and doctor-diagnosed COPD. Physicians tend to
      underdiagnose COPD in women who present to primary care clinics. Whereas around
      15% of enrolled women had evidence of COPD with FEV1/FVC < 70% after
      bronchodilators, only 4.8% were physician-diagnosed. Asthma did not appear to be
      a significant spirometric finding in these female subjects, although around 11%
      had physician-diagnosed asthma. One limitation is FEV1/FVC < 70% could have also
      resulted from uncontrolled asthma. The same limitation has been reported by the
      Proyecto Latinoamericano de Investigacion en Obstruccion Pulmonar (PLATINO)
      study. CONCLUSION: Contrary to popular belief in developing countries, women
      exposed to tobacco smoke, whether active or passive, and whether by cigarettes or
      narghiles, like men are at increased risk for the development of COPD, although
      cultural habits and taboos may decrease the risk of active smoking in some women.
      RECOMMENDATIONS: These findings will be considered for country and region
      strategy for noncommunicable diseases, to overcome underdiagnosis of CRD in
      women, fight widespread female cigarette and narghile smoking, and promote
      behavioral research in this field.

PMID- 24124360
TI  - Enhanced penetration into 3D cell culture using two and three layered gold
      nanoparticles.
AB  - Nano-scale particles sized 10-400 nm administered systemically preferentially
      extravasate from tumor vasculature due to the enhanced permeability and retention
      effect. Therapeutic success remains elusive, however, because of inhomogeneous
      particle distribution within tumor tissue. Insufficient tumor vascularization
      limits particle transport and also results in avascular hypoxic regions with non
      proliferating cells, which can regenerate tissue after nanoparticle-delivered
      cytotoxicity or thermal ablation. Nanoparticle surface modifications provide for
      increasing tumor targeting and uptake while decreasing immunogenicity and
      toxicity. Herein, we created novel two layer gold-nanoshell particles coated with
      alkanethiol and phosphatidylcholine, and three layer nanoshells additionally
      coated with high-density-lipoprotein. We hypothesize that these particles have
      enhanced penetration into 3-dimensional cell cultures modeling avascular tissue
      when compared to standard poly(ethylene glycol) (PEG)-coated nanoshells. Particle
      uptake and distribution in liver, lung, and pancreatic tumor cell cultures were
      evaluated using silver-enhancement staining and hyperspectral imaging with dark
      field microscopy. Two layer nanoshells exhibited significantly higher uptake
      compared to PEGylated nanoshells. This multilayer formulation may help overcome
      transport barriers presented by tumor vasculature, and could be further
      investigated in vivo as a platform for targeted cancer therapies. 

PMID- 24124361
TI  - New strategy for monitoring targeted therapy: molecular imaging.
AB  - Targeted therapy is becoming an increasingly important component in the treatment
      of cancer. How to accurately monitor targeted therapy has been crucial in
      clinical practice. The traditional approach to monitor treatment through imaging
      has relied on assessing the change of tumor size by refined World Health
      Organization criteria, or more recently, by the Response Evaluation Criteria in
      Solid Tumors. However, these criteria, which are based on the change of tumor
      size, show some limitations for evaluating targeted therapy. Currently, genetic
      alterations are identified with prognostic as well as predictive potential
      concerning the use of molecularly targeted drugs. Conversely, considering the
      limitations of invasiveness and the issue of expression heterogeneity, molecular
      imaging is better able to assay in vivo biologic processes noninvasively and
      quantitatively, and has been a particularly attractive tool for monitoring
      treatment in clinical cancer practice. This review focuses on the applications of
      different kinds of molecular imaging including positron emission tomography-,
      magnetic resonance imaging-, ultrasonography-, and computed tomography-based
      imaging strategies on monitoring targeted therapy. In addition, the key
      challenges of molecular imaging are addressed to successfully translate these
      promising techniques in the future. 

PMID- 24124362
TI  - The migration of synthetic magnetic nanoparticle labeled dendritic cells into
      lymph nodes with optical imaging.
AB  - BACKGROUND: The successful biotherapy of carcinoma with dendritic cell (DC)
      vaccines pivotally relies on DCs' migratory capability into lymph tissues and
      activation of T cells. Accurate imaging and evaluation of DC migration in vivo
      have great significance during antitumor treatment with DC vaccine. We herein
      examined the behavior of DCs influenced by synthetic superparamagnetic iron oxide
      (SPIO) nanoparticle labeling. METHODS: gamma-Fe2O3 nanoparticles were prepared
      and DCs, which were induced from bone marrow monocytes of enhanced green
      fluorescent protein (EGFP) transgenic mice, were labeled. The endocytosis of the
      SPIO, surface molecules, cell apoptosis and fluorescence intensity of EGFP-DCs
      were displayed by Prussian blue staining and flow cytometry (FCM), respectively.
      After EGFP-DCs, labeled with SPIO, were injected into footpads (n = 5) for 24
      hours, the mice were examined in vivo by optical imaging (OPI). Meanwhile,
      confocal imaging and FCM were applied, respectively, to detect the migration of
      labeled DCs into draining lymph nodes. RESULTS: Nearly 100% of cells were labeled
      by the SPIO, in which the intracellular blue color gradually deepened and the
      iron contents rose with the increase of labeling iron concentrations. In
      addition, cell apoptosis and the surface molecules on DCs were at similar levels
      after SPIO labeling. After confirming that the fluorescence intensity of EGFP on
      DCs was not influenced by SPIO, the homing ability of EGFP-DCs labeled with SPIO
      displayed that the fluorescence intensity and the ratios of EGFP-DCs in draining
      lymph nodes were gradually decreased with the increase of labeling iron
      concentrations. CONCLUSION: The synthetic SPIO nanoparticles possess perfect
      labeling ability and biocompatibility. Moreover, DCs labeled with a low dose of
      SPIO showed stronger migratory capability in vivo.

PMID- 24124363
TI  - Preparation and characterization of gadolinium-loaded PLGA particles surface
      modified with RGDS for the detection of thrombus.
AB  - Thrombotic disease is a leading cause of death and disability worldwide. The
      development of magnetic resonance molecular imaging provides potential promise
      for early disease diagnosis. In this study, we explore the preparation and
      characterization of gadolinium (Gd)-loaded poly (lactic-co-glycolic acid) (PLGA)
      particles surface modified with the Arg-Gly-Asp-Ser (RGDS) peptide for the
      detection of thrombus. PLGA was employed as the carrier-delivery system, and a
      double emulsion solvent-evaporation method (water in oil in water) was used to
      prepare PLGA particles encapsulating the magnetic resonance contrast agent Gd
      diethylenetriaminepentaacetic acid (DTPA). To synthesize the Gd-PLGA/chitosan
      (CS)-RGDS particles, carbodiimide-mediated amide bond formation was used to graft
      the RGDS peptide to CS to form a CS-RGDS film that coated the surface of the PLGA
      particles. Blank PLGA, Gd-PLGA, and Gd-PLGA/CS particles were fabricated using
      the same water in oil in water method. Our results indicated that the RGDS
      peptide successfully coated the surface of the Gd-PLGA/CS-RGDS particles. The
      particles had a regular shape, smooth surface, relatively uniform size, and did
      not aggregate. The high electron density of the Gd-loaded particles and a
      translucent film around the particles coated with the CS and CS-RGDS films could
      be observed by transmission electron microscopy. In vitro experiments
      demonstrated that the Gd-PLGA/CS-RGDS particles could target thrombi and could be
      imaged using a clinical magnetic resonance scanner. Compared with the Gd-DTPA
      solution, the longitudinal relaxation time of the Gd-loaded particles was
      slightly longer, and as the Gd-load concentration increased, the longitudinal
      relaxation time values decreased. These results suggest the potential of the Gd
      PLGA/CS-RGDS particles for the sensitive and specific detection of thrombus at
      the molecular level. 

PMID- 24124364
TI  - The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model
      of hepatocellular carcinoma.
AB  - BACKGROUND/AIM: A local nanotherapy (LNT) combining the therapeutic efficacy of
      trans-arterial embolization, nanoparticles, and p53 gene therapy has been
      previously presented. The study presented here aimed to further improve the
      incomplete tumor eradication and limited survival enhancement and to elucidate
      the molecular mechanism of the LNT. METHODS: In a tumor-targeting manner,
      recombinant expressing plasmids harboring wild-type p53 and Rb were either co
      transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L
      lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol(r) (Guerbet,
      Villepinte, France) emulsion via the hepatic artery. Subsequent co-expression of
      p53 and Rb proteins within the treated tumors was investigated by Western
      blotting and in situ analysis by laser-scanning confocal microscopy. The
      therapeutic effect was evaluated by the tumor growth velocity, apoptosis and
      necrosis rates, their sensitivity to Adriamycin(r) (ADM), mitomycin C, and
      fluorouracil, the microvessel density of tumor tissue, and the survival time of
      animals. Eventually, real-time polymerase chain reaction and enhanced
      chemiluminescence Western blotting were used to investigate the expressive
      changes of important genes related to the therapy. RESULTS: The administration
      procedure proved safe for the rabbits' liver function, the p53 plus Rb LNT showed
      significantly better antitumoral effect and lower expression of malignant genes
      than the p53 or Rb LNT, although no significant difference was observed in animal
      survival when the p53 plus Rb LNT was compared with the p53 LNT. CONCLUSION: Rb
      works synergistically with p53 in combined therapy mediated by a poly-L-lysine
      modified hydroxyapatite nanoparticle nanoplex to augment the antitumoral effect
      through the downregulated expression of important genes related to apoptosis,
      necrosis, growth, differentiation and multidrug resistance of tumor cells. LNT
      with p53 and Rb is potentially an effective antitumor therapy for hepatocellular
      carcinoma.

PMID- 24124365
TI  - Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and
      in vivo evaluation.
AB  - Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal
      herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely
      used for the treatment of fever, inflammation, and other conditions. Due to
      baicalin's poor solubility in water, its absolute bioavailability after oral
      administration is only 2.2%. The objective of this study was to develop a novel
      baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin.
      Based on the result of pseudoternary phase diagram, the nanoemulsion formulation
      consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl
      myristate, and water (1:2:1.5:3.75:8.25, w/w) was selected for further study.
      Baicalin-loaded nanoemulsions (BAN-1 and BAN-2) were prepared by internal or
      external drug addition and in vivo and in vitro evaluations were performed. The
      results showed that the mean droplet size, polydispersity index, and drug content
      of BAN-1 and BAN-2 were 91.2 +/- 2.36 nm and 89.7 +/- 3.05 nm, 0.313 +/- 0.002
      and 0.265 +/- 0.001, and 98.56% +/- 0.79% and 99.40% +/- 0.51%, respectively.
      Transmission electron microscopy revealed spherical globules and confirmed
      droplet size analysis. After dilution 30-fold with water, the solubilization
      capacity of BAN-1 and BAN-2 did not change. In vitro release results showed
      sustained-release characteristics. BAN-1 formulation was stable for at least 6
      months and was more stable than BAN-2. In rats, the area under the plasma drug
      concentration-time curve value of BAN-1 was 1.8-fold and 7-fold greater than
      those of BAN-2 and free baicalin suspension after oral administration at a dose
      of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded
      nanoemulsion formulation, in particular BAN-1, was very effective for improving
      the oral bioavailability of baicalin and exhibited great potential for future
      clinical application. 

PMID- 24124366
TI  - Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide
      nanoparticles for targeting and magnetic resonance imaging of breast cancer.
AB  - Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer
      poly(ethylene oxide)-block-poly(gamma-methacryloxypropyltrimethoxysilane) (PEO-b
      PgammaMPS) were investigated for improving cell targeting by reducing nonspecific
      uptake. Conjugation of a HER2 antibody, Herceptin(r), or a single chain fragment
      (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b
      PgammaMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti
      HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3,
      a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2
      underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong
      reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but
      not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission
      electron microscopy revealed internalization of the receptor-targeted
      nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated
      and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7
      mouse macrophages in vitro. The developed IONPs showed a long blood circulation
      time (serum half-life 11.6 hours) in mice and low accumulation in both the liver
      and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice
      bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance
      imaging revealed signal reduction in the tumor as a result of the accumulation of
      the targeted IONPs. 

PMID- 24124367
TI  - Targeted hyperthermia after selective embolization with ferromagnetic
      nanoparticles in a VX2 rabbit liver tumor model.
AB  - BACKGROUND: The purpose of this study was to observe the effect and feasibility
      of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit
      liver model exposed to an alternating magnetic field after embolization with
      ferromagnetic nanoparticles. METHODS: Forty rabbits containing implanted hepatic
      VX2 carcinomas were divided into four groups, each containing ten rabbits.
      Fourteen days after tumor transplantation, we opened the abdomen to observe the
      size and shape of the tumor. A transfemoral retrograde approach was then used for
      hepatic arterial catheterization in groups B, C, and D to perform angiography and
      embolization. The next day, three rabbits in group B and all rabbits in group D
      were exposed to an alternating magnetic field, and the temperature was recorded
      simultaneously in the center of the tumor, at the edge of the tumor, and in the
      normal liver parenchyma. On day 28, all animals was euthanized to observe changes
      in the implanted liver tumor and the condition of the abdomen. A pathologic
      examination was also done. RESULTS: Before surgery, there was no significant
      difference in tumor volume between the four groups. Three different temperature
      points (cen ter of the tumor, edge of the tumor, and in the normal liver
      parenchyma) of group B under an alternating magnetic field were 37.2 degrees C +/
      1.1 degrees C, 36.8 degrees C +/- 1.2 degrees C, and 36.9 degrees C +/- 2.1
      degrees C, none of which were significantly different from pretreatment values.
      Three points basal temperature in group D showed no significant difference (F =
      1.038, P = 0.413). Seven to 26 minutes after hyperthermia, the temperature at the
      center of the tumor and at the edge of the tumor in group D was significantly
      different from the corresponding points in group B and from normal liver tissue
      in group D (F(B-D center) = 5.431, P(B-D center) = 0.041, F(B-D edge) = 9.744,
      P(B-D edge) = 0.011; F(D) = 8.379, P(D) = 0.002). The highest temperature
      recorded at the rim of the tumor was 46 degrees C in group D. Fourteen days
      later, the tumor volume in the four groups was group A 31.4 +/- 20.6 cm(3), group
      B 26.7 +/- 18.2 cm(3), group C 28.7 +/- 9.1 cm(3), and group D 25.8 +/- 13.9
      cm(3), with no significant difference found between the groups (F = 0.218, P =
      0.883). The increase in tumor volume was greatest in group A and least in group
      D, while that in groups B and D was similar. CONCLUSION: It is feasible to treat
      a VX2 tumor in an alternating magnetic field after embolization with magnetic
      nanoparticles without a significant effect on the surrounding normal liver
      parenchyma.

PMID- 24124368
TI  - Efficacy and safety of dendrimer nanoparticles with coexpression of tumor
      necrosis factor-alpha and herpes simplex virus thymidine kinase in gene
      radiotherapy of the human uveal melanoma OCM-1 cell line.
AB  - Human uveal melanoma is the most common primary intraocular tumor, and
      brachytherapy is one of the most common and effective treatment strategies. In
      order to find a safer and more effective way to increase the radio sensitivity of
      the tumor, we tried to use the dendrimer nanoparticle performing coexpression
      gene radiotherapy. In this study, we constructed recombinant DNA plasmids (early
      growth response-1 tumor necrosis factor-alpha [pEgr1-TNFalpha], pEgr1 thymidine
      kinase [TK], and pEgr1-TNFalpha-TK) according to the Egr1 promoter sequence. The
      sequences of human TNFalpha and herpes simplex virus (HSV) TK that were published
      by GenBank. Agarose gel electrophoresis and DNA sequencing had proven that we
      constructed the double-gene recombined plasmids pEgr1-TNF-TK correctly, as well
      as the plasmids pEgr1-TNFalpha and pEgr1-TK. The dendrimer nanoparticles combined
      with plasmid DNA as dendriplexes were verified with agarose gel electrophoresis
      and observed by transmission electron microscopy (TEM) and scanning electron
      microscopy to define size and shape. Zeta potential was measured using a
      Zetasizer analyzer. Optimal size and neutral zeta-potential characteristics of
      dendriplexes were achieved for the transfection studies. DNase I examination
      proved that the dendriplexes could protect plasmid DNA for at least 6 hours. The
      recombinant plasmids were transfected with dendrimer nanoparticles into the human
      choroidal melanoma OCM-1 cell line, followed by exposure to iodine-125 ((125)I)
      after transfection. After transfection with dendrimer nanoparticles and the
      irradiation of (125)I, the gene expressions of TNFalpha and HSV1-TK were
      significantly increased at the protein level by enzyme-linked immunosorbent assay
      and Western blot analysis in OCM-1 cells. The cellular morphology of OCM-1 cells
      altering was observed by TEM, and a decrease in cell proliferation was revealed
      in cell-growth curves. Flow cytometry of annexin V/propidium iodide double-dyeing
      apoptosis and caspase-3 fluorescence staining showed that this treatment method
      could turn transfected OCM-1 cells into apoptosis and necrosis by the effects of
      the gene expression. This study indicated that the dendrimer nanoparticles with
      coexpression of TNF-alpha and HSV1-TK gene therapy are effective and safe and can
      provide us with a novel strategy to treat human uveal melanoma in the future. 

PMID- 24124369
TI  - Hyaluronic acid-coated bovine serum albumin nanoparticles loaded with brucine as
      selective nanovectors for intra-articular injection.
AB  - OBJECTIVE: To evaluate the potential of hyaluronic acid (HA)-coated bovine serum
      albumin nanoparticles (BSANPs) as a novel chondrocyte-targeting drug-delivery
      nanomedicine. METHODS: The HA-BSANPs were characterized by dynamic light
      scattering, transmission electron microscopy, differential scanning calorimetry,
      and X-ray diffraction. Fluorescence imaging was used to visualize the
      distribution of nanoparticles after intra-articular injection. The chondrocyte
      targeting efficiency and cellular uptake mechanism of HA-BSANPs were investigated
      using endocytic inhibitors. RESULTS: HA-BSANPs were successfully prepared with HA
      coating the surface and amorphous drug in the core. Compared with BSANPs, HA
      BSANPs exhibited improved uptake by chondrocytes through a receptor-mediated
      active uptake mechanism. The endocytosis process of BSANPs and HA-BSANPs involved
      clathrin-mediated endocytosis, caveolae-mediated endocytosis, and
      macropinocytosis. No apparent thickening or hyperplasia of the synovium was
      observed in either BSANPs or HA-BSANPs. The HA-BSANPs could reside in the
      articular cavity of rats for more than 14 days, which was significantly longer
      than BSANPs. CONCLUSION: HA-BSANPs are a promising carrier for articular-related
      diseases due to elongated articular residence and improved chondrocytic
      accumulation.

PMID- 24124370
TI  - Attachment styles in children affected by migraine without aura.
AB  - BACKGROUND: In recent years, great attention has been given to the presence of
      psychological problems and psychiatric comorbidity that are also present in
      children affected by primary headaches. The relationship between pain and
      attachment has been identified, and it may be that pain perception may change in
      relation with specific attachment styles. The aim of the present study was to
      assess the prevalent attachment style and verify its putative relationship and
      correlation with the main characteristics of migraine attacks, in school-aged
      children affected by migraine without aura (MoA). MATERIALS AND METHODS: The
      study population consisted of 219 children (103 males, 116 females) aged between
      6 and 11 years (mean 8.96 +/- 2.14 years), consecutively referred for MoA
      compared with 381 healthy controls (174 males, 207 females; mean age 9.01 +/-
      1.75 years) randomly selected from schools. All the children were classified
      according to the attachment typologies of the Italian modified version of the
      Separation Anxiety Test; monthly headache frequency and mean headache duration
      were assessed from daily headache diaries kept by all the children. Headache
      intensity was assessed on a visual analog scale. The chi-square test and t-test,
      where appropriate, were applied, and the Spearman rank correlation test was
      applied to explore the relationship between the types of attachment style and
      clinical aspects of MoA. RESULTS: The MoA group showed a significantly higher
      prevalence of type A (avoidant) attachment (P<0.001) and a significantly lower
      prevalence of type B (secure) attachment (P<0.001) compared with the control
      group. Moreover, the Spearman rank correlation analysis showed a significant
      relationship between MoA characteristics and the attachment style of MoA
      children. CONCLUSION: The main findings of the present study were the higher
      prevalence among MoA children of the avoidant attachment style (type A) and the
      significantly lower prevalence of the secure style attachment (type B) compared
      with the normal controls, suggesting that the study of psychiatric comorbidity in
      pediatric headache may be enriched by this new aspect of analysis.

PMID- 24124371
TI  - Bridging, switching or drug holidays - how to treat a patient who stops
      natalizumab?
AB  - Natalizumab (NAT) was the first monoclonal antibody to be approved for the
      treatment of relapsing-remitting multiple sclerosis (RRMS). While pivotal and
      postmarketing studies have showed considerable and sustained efficacy of NAT in
      RRMS, the increasing incidence of therapy-associated progressive multifocal
      leukoencephalopathy (PML), a brain infection caused by the John Cunningham virus
      (JCV), is a risk associated with long-term therapy. The risk for therapy
      associated PML is highest in so-called "triple risk" patients. Therefore, long
      term NAT-treated, immunosuppressive-pretreated, and JCV antibody-positive
      patients often discontinue NAT therapy. However, until now, it is not known which
      treatment strategy should be followed after NAT cessation. Since disease activity
      returns to pretreatment levels, or even above, within 4-7 months from the last
      infusion of NAT, patients who stop NAT are at considerable risk of relapse and
      worsening of multiple sclerosis (MS)-related disability. Several strategies have
      been applied to prevent the recurrence of disease activity after discontinuation
      of NAT. Of these, bridging with intravenous methylprednisolone, and switching to
      glatiramer acetate or interferon beta (IFN-beta) do not seem to be effective
      enough. More promising results have been obtained in retrospective studies and
      case series with fingolimod (FTY), an alternative escalation therapy for RRMS,
      although some patients have showed a severe disease rebound after starting FTY
      treatment. The time interval between the discontinuation of NAT and the start of
      FTY might affect the recurrence of disease activity. Long-term data about the
      efficacy and safety of FTY treatment after cessation of NAT are urgently needed
      and should be further investigated. Prospective studies are warranted, to
      optimize treatment strategies for RRMS patients who discontinue NAT, especially
      because new therapies will be available in the very near future. 

PMID- 24124372
TI  - Randomized controlled study of the antipyretic efficacy of oral paracetamol,
      intravenous paracetamol, and intramuscular diclofenac in patients presenting with
      fever to the emergency department.
AB  - BACKGROUND: Fever is a common problem in adults visiting the emergency
      department. Extensive studies have been done in children comparing the efficacy
      of various antipyretics. However, studies on the efficacy of antipyretic drugs in
      adults are very scarce. To the best of our knowledge, no controlled trial has
      been carried out comparing the antipyretic efficacy of paracetamol (oral and
      intravenous) and intramuscular diclofenac in adults. METHODS: In this parallel
      group, open-label trial, participants aged 14-75 years presenting with fever who
      had a temperature of more than 38.5 degrees C were enrolled and treated.
      Participants were randomly allocated to receive treatment with 1,000 mg oral
      paracetamol (n = 145), 1,000 mg intravenous paracetamol (n = 139), or 75 mg
      intramuscular diclofenac (n = 150). The primary outcome was degree of reduction
      in mean oral temperature at 90 minutes. The efficacy of diclofenac versus oral
      and intravenous paracetamol was assessed by superiority comparison. Analysis was
      done using intention to treat principles. RESULTS: After 90 minutes, all three
      groups showed a significant reduction in mean temperature, with intramuscular
      diclofenac showing the greatest reduction (-1.44 +/- 0.43, 95% confidence
      interval [CI] -1.4 to -2.5) and oral paracetamol the least (-1.08 +/- 0.51, 95%
      CI -0.99 to -2.2). After 120 minutes, there was a significant difference observed
      in the mean change from baseline temperature between the three treatment groups
      (P < 0.0001). Significant changes in temperature were observed in favor of
      intramuscular diclofenac over oral and intravenous paracetamol at each time point
      from 60 minutes through 120 minutes inclusive. CONCLUSION: Both intramuscular
      diclofenac and intravenous paracetamol showed superior antipyretic activity than
      oral paracetamol. However, in view of its ease of administration, intramuscular
      diclofenac can be used as a first-choice antipyretic in febrile adults in the
      emergency department.

PMID- 24124373
TI  - Lifetime opiate exposure as an independent and interactive cardiovascular risk
      factor in males: a cross-sectional clinical study.
AB  - INTRODUCTION: While several studies have identified an increased incidence of
      cardiovascular disorders in opiate dependence, neither opiates as a
      cardiovascular risk factor nor their effect on central arterial function has been
      considered. METHODS: Pulse wave analysis (SphygmoCor, AtCorMedical Pty Limited,
      Sydney, NSW, Australia) was undertaken on a cohort of controls and opiate
      dependent patients and the results compared to their lifetime opiate exposure.
      RESULTS: Controls (N = 401) were compared with 465 opiate dependent men. The mean
      (log) ages were different and were found to be 28.80 +/- 0.49 years versus 35.02
      +/- 0.39 years (P < 0.0001), respectively. Of the opiate dependent group, 87.7%
      were treated with buprenorphine, 8.8% with methadone, and 3.4% with naltrexone.
      Multiple regression analysis was used to adjust for chronologic age (CA). At CA
      of 60 years, the modeled age in the controls was 66.40 years, and that in the
      addicted group was 73.11 years, an advancement of 6.71 years, or 10.10%.
      Exacerbations of age dependent changes in central arterial stiffness, central
      pressures, pulse rate, ejection duration, diastolic duration, and subendocardial
      perfusion ratio by opiate dependence were all noted (P < 0.05). Current heroin
      dose, heroin duration, and the dose duration interaction were all significantly
      related to the vascular (or "reference") age (RA)/CA ratio (all P < 0.006). After
      multivariate adjustment, the opiate dose duration was independently predictive of
      RA (P < 0.02). Opiate dose and/or duration were included in a further 25 terms.
      CONCLUSION: These data show that opiate use is not benign for the male
      cardiovascular system, but has a dose response relationship to central arterial
      stiffness and thus cardiovascular aging, acting independently and interactively
      with established cardiovascular risk factors. These findings imply accelerated
      organismal aging.

PMID- 24124374
TI  - Steady-state bioavailability of prescription omega-3 on a low-fat diet is
      significantly improved with a free fatty acid formulation compared with an ethyl
      ester formulation: the ECLIPSE II study.
AB  - The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is
      dependent on the presence of intestinal lipases and is highest during consumption
      of high-fat meals. Given that patients with cardiovascular disease are advised to
      reduce dietary fat intake, potentially lowering the bioavailability and
      therapeutic benefit, the hypothesis that FFA forms provide for higher
      bioavailability compared with EE forms under low-fat diet conditions was tested
      where the pharmacokinetics of the FFA form (EpanovaTM) were compared with those
      of an ethyl ester form (Lovaza(r)) following repeat dosing. Fifty-two healthy
      male and female subjects were equally allocated to one of two open-label,
      parallel-group cohorts. Following a Therapeutic Lifestyle Changes diet for a
      minimum of 7 days, blood samples were drawn for endogenous values for EPA and DHA
      over a 24-hour period. Subjects were then administered 4 * 1 g capsules of either
      Epanova (OM3 FFA) or Lovaza (OM3 EE) once daily for 14 days, following which
      serial blood samples were drawn over a 24-hour period to characterize the
      bioavailability of EPA and DHA from the respective formulations. In addition,
      changes from baseline in lipid profile were explored. Systemic bioavailability,
      as measured by area under the curve from time zero to 24 hours (AUC(0-tau)) and
      the maximum measured plasma concentrations during the 0-24 hour dosing interval
      (C(max,ss)) of unadjusted total plasma EPA + DHA were approximately 3-fold and
      3.9-fold higher, respectively, for Epanova relative to Lovaza. Following baseline
      adjustment, the magnitude of difference in bioavailability was approximately 5.8
      fold and 6.5-fold higher in AUC(0-tau) and C(max,ss), respectively, for Epanova
      relative to Lovaza. Serum triglycerides were reduced by a significantly greater
      extent (P = 0.013) for Epanova relative to Lovaza (21% versus 8%). The
      bioavailability of the FFA forms of EPA and DHA in Epanova are significantly
      greater than the bioavailability from the EE forms present in Lovaza under low
      fat dietary conditions normally recommended for patients with cardiovascular
      disease. This increased bioavailability may lead to improved triglyceride
      lowering in patients with hypertriglyceridemia.

PMID- 24124376
TI  - Postmarketing safety experience with edoxaban in Japan for thromboprophylaxis
      following major orthopedic surgery.
AB  - PURPOSE: Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor
      approved in Japan for the prevention of venous thromboembolism following major
      orthopedic surgery. Currently, edoxaban is in Phase III clinical development for
      the prevention of stroke and systemic embolic events in patients with atrial
      fibrillation, and for the treatment and prevention of recurrences of venous
      thromboembolism. This report describes the adverse drug reactions (ADRs)
      spontaneously reported during early postmarketing phase vigilance from the time
      of its commercial launch in Japan. MATERIALS AND METHODS: All spontaneously
      reported ADRs following edoxaban use received by Daiichi Sankyo during early
      postmarketing phase vigilance from July 19, 2011, to January 18, 2012, were
      entered into the safety database and included in this review. Approximately
      20,000 patients were estimated to have been treated with edoxaban. RESULTS: The
      mean age of patients was 74.2 years, their mean weight was 59.4 kg, and
      approximately 70% were female. A total of 67 ADRs were reported in 56 patients,
      of which the majority included bleeding events (51 ADRs in 42 patients). Of
      these, 15 ADRs (in 14 patients) were serious, including cerebral hemorrhage (n =
      1), gastric hemorrhage (n = 2; gastric hemorrhage [n = 1] and gastric ulcer
      hemorrhage [n = 1]), and surgical-site hemorrhage (n = 12; hemorrhage [n = 6],
      subcutaneous hemorrhage [n = 3], wound hemorrhage [n = 2], and wound hematoma [n
      = 1]). Most ADRs occurred within the first week of treatment and there were no
      fatalities. Nonserious ADRs associated with bleeding that occurred in >1 patient
      included subcutaneous hemorrhage (n = 9), wound hemorrhage (n = 5),
      postprocedural hematoma (n = 4), anemia (n = 4), and hemarthrosis (n = 3). Other
      nonserious ADRs not associated with bleeding and occurring in >1 patient included
      abnormal hepatic function (n = 4) and diarrhea (n = 2). CONCLUSION: Safety data
      from the first 6 months of postmarketing experience with edoxaban did not
      identify any unforeseen safety signals, consistent with the known safety profile
      of edoxaban.

PMID- 24124375
TI  - Comprehensive overview: efficacy, tolerability, and cost-effectiveness of
      irbesartan.
AB  - BACKGROUND: Hypertension represents a major health problem, affecting more than
      one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is
      considered to be a highly effective treatment in the management of hypertension.
      The purpose of this review is to evaluate the efficacy, safety and tolerability
      profile, and cost-effectiveness of treatment with irbesartan in hypertension.
      METHODS: A review of the literature was conducted using the electronic PubMed and
      Cochrane Library databases and the Health Economic Evaluations Database of search
      terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and
      the results were utilized. RESULTS: Findings from the present analysis show that
      irbesartan either as monotherapy or in combination with other antihypertensive
      agents can achieve significant reductions in blood pressure, both systolic and
      diastolic, compared with alternative treatment options. Irbesartan was also found
      to have a renoprotective effect independent of its blood pressure-lowering in
      patients with type 2 diabetes and nephropathy. Furthermore, irbesartan
      demonstrated an excellent safety and tolerability profile, with either lower or
      equal adverse events compared with placebo and other alternative treatments. In
      terms of economic analyses, compared with other antihypertensive therapy
      alternatives, irbesartan was found to be a preferred option, that is less costly
      and more effective. CONCLUSION: The evidence indicates that treating patients
      with hypertension alone or with type 2 diabetes and nephropathy using irbesartan
      can control hypertension, prolong life, and reduce costs in relation to existing
      alternatives.

PMID- 24124377
TI  - Modified relaxation technique for treating hypertension in Thai postmenopausal
      women.
AB  - AIM: To examine the effectiveness of a modified relaxation (MR) technique in
      reducing blood pressure levels in Thai postmenopausal women with mild
      hypertension, compared with a control group who received health education.
      METHODS: This is a 16-week, randomized, parallel, open-label, controlled trial in
      a menopausal clinic in a tertiary health care center in Northeastern Thailand.
      The intervention group received a 60-minute session of MR training and were
      encouraged to practice 15-20 minutes a day, at least 5 days a week. The control
      group received lifestyle education, including diet and exercise. The primary and
      secondary outcomes were systolic and diastolic blood pressure (SBP and DBP).
      RESULTS: Of 432 participants, 215 and 217 were randomly allocated to the MR and
      control groups, respectively. Of those, 167 participants in the MR group and 175
      participants in the control group completed the study. The SBP was significantly
      more reduced in the MR group, with a mean of 2.1 mmHg (P < 0.001). There was no
      significant difference between groups on the changed DBP. CONCLUSION: The MR
      technique may be effective in lowering SBP in Thai postmenopausal women visiting
      a menopause clinic. Its efficacy may be observed as soon as 4 weeks after start
      of treatment. Long-term and combined relaxation therapy and antihypertensive
      agents are warranted in a large cohort of this population. This trial is
      registered in clinicaltrials.gov (number NCT01429662).

PMID- 24124378
TI  - Administration of care to older patients in transition from hospital to home care
      services: home nursing leaders' experiences.
AB  - BACKGROUND: Older persons in transition between hospital and home care services
      are in a particularly vulnerable situation and risk unfortunate consequences
      caused by organizational inefficiency. The purpose of the study reported here was
      to elucidate how home nursing leaders experience the administration of care to
      older people in transition from hospital to their own homes. METHODS: A
      qualitative study design was used. Ten home nursing leaders in two municipalities
      in southern Norway participated in individual interviews. The interview texts
      were audio taped, transcribed verbatim and analyzed by use of a phenomenological
      hermeneutic approach. RESULTS: Three main themes and seven subthemes were deduced
      from the data. The first main theme was that the home nursing leaders felt
      challenged by the organization of home care services. Two subthemes were
      identified related to this. The first was that the leaders lacked involvement in
      the transitional process, and the second was that they were challenged by
      administration of care being decided at another level in the municipality. The
      second main theme found was that the leaders felt that they were acting in a
      shifting and unsettled context. Related to this, they had to adjust internal
      resources to external demands and expectations, and experienced lack of
      communication with significant others. The third main theme identified was that
      the leaders endeavored to deliver care in accordance with professional values.
      The two related subthemes were, first, that they provided for appropriate
      internal systems and routines, and, second, that they prioritized available
      professional competence, and made an effort to promote a professional culture.
      CONCLUSION: To meet the complex needs of the patients in a professional way, the
      home nursing leaders needed to be flexible and pragmatic in their administration
      of care. This involved utilizing available professional competence appropriately.
      The coordination and communication between the different organizational levels
      and units were pointed out as major factors requiring improvement.

PMID- 24124380
TI  - AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer
      tissue and cell lines.
AB  - BACKGROUND: Gallbladder carcinoma is a highly malignant tumor and a public health
      problem in some parts of the world. It is characterized by a poor prognosis and
      its resistance to radio and chemotherapy. There is an urgent need to develop
      novel therapeutic alternatives for the treatment of gallbladder carcinoma. The
      mammalian target of the rapamycin (mTOR) signaling pathway is activated in about
      50% of human malignancies, and its role in gallbladder carcinoma has previously
      been suggested. In the present study, we investigated the phosphorylation status
      of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues
      and evaluated the effect of three mTOR inhibitors on cell growth and migration in
      gallbladder carcinoma cell lines. METHODS: Immunohistochemical staining of
      phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified
      according to lesion type as dysplasia, early carcinoma, or advanced carcinoma.
      Protein expression of AKT/mTOR members was also evaluated in eight gallbladder
      carcinoma cell lines by Western blot analysis. We selected two gallbladder
      carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin,
      RAD001, and AZD8055 on cell viability, cell migration, and protein expression.
      RESULTS: Our results showed that phospho-p70S6K is highly expressed in dysplasia
      (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%,
      121/137). No statistical correlation was observed between phospho-p70S6K status
      and any clinical or pathological features, including age, gender, ethnicity, wall
      infiltration level, or histological differentiation (P < 0.05). In vitro
      treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell
      migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB
      cancer cells (P < 0.001). CONCLUSION: Our findings confirm the upregulation of
      this signaling pathway in gallbladder carcinoma and provide a rationale for the
      potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder
      carcinoma.

PMID- 24124381
TI  - Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel
      combination therapy in a case of advanced breast cancer.
AB  - Bevacizumab when combined with chemotherapy exerts significant activity against
      many solid tumors through tumor angiogenesis inhibition; however, it can induce
      severe side effects. We report the rare case of a 27-year-old premenopausal woman
      with locally advanced breast cancer that was marked by rapid tumor necrosis
      followed by massive hemorrhage shortly after bevacizumab and paclitaxel
      administration. On the basis of histopathological examination of a biopsy
      specimen and computed tomography findings, she was diagnosed with stage IV
      estrogen and progesterone receptor-negative and human epidermal growth factor
      receptor type 2-positive breast cancer with multiple organ metastases when she
      had entered gestational week 24. Cyclophosphamide, Adriamycin(r), fluorouracil
      therapy was initiated, but multiple liver metastases continued to progress. A
      healthy fetus was delivered by induced delivery and trastuzumab-based treatment
      was initiated. Although the multiple liver metastases were controlled
      successfully by trastuzumab combined with paclitaxel, the primary tumor continued
      to expand even after subsequent administration of three other treatment regimens
      including anti-human epidermal growth factor receptor type 2 agents and cytotoxic
      drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and
      bevacizumab was subsequently initiated. Following therapy initiation, however,
      the large tumor occupying the patient's entire left breast became necrotic and
      ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5
      weeks after bevacizumab-based therapy initiation. Although hemostasis was
      achieved by manual compression, the patient required blood transfusion for the
      massive blood loss. She eventually succumbed to respiratory failure. This case
      report demonstrates that primary breast cancer lesions with skin involvement have
      the potential to cause massive hemorrhage after bevacizumab-based treatment. 

PMID- 24124382
TI  - Communicable disease-related sudden death in the 21st century in Nigeria.
AB  - BACKGROUND: Some cases of sudden death (SD) have been attributed to communicable
      diseases (CD) in middle- and low-income countries of the world even in this 21st
      century. CDs produce clinical symptoms and signs over several days before
      culminating in death. They are also amenable to treatment with antimicrobials if
      affected persons present early. We sought to find out the incidence of CD-related
      SD at the Ladoke Akintola University of Technology Teaching Hospital (Osogbo,
      Osun State, Nigeria) - a tertiary health facility in southwest Nigeria - and the
      prevailing associated factors. METHODS: We conducted a retrospective study of CD
      related SD in adult patients aged 18 years and older that occurred from January
      2003 to December 2011. The Statistical Package for the Social Sciences version 16
      was used for analysis of the generated data. Percentages and frequencies were
      calculated. RESULTS: There were 17 (39.6%) CD-related SDs out of the 48 cases of
      SD studied. CD-related SD also accounted for 2.4% of all adult medical
      admissions. The mean age of the patients was 37.6 +/- 11.6 years, age range of 25
      62 years, mode of 25 years, and median 34 years. The male-to-female ratio was
      1.8:1. Typhoid sepsis was responsible for SD in 47.1% of patients, pulmonary
      tuberculosis in 17.7% of patients, and lobar pneumonia in 17.7% of patients. The
      most affected age group was the 20-29-year-old group (41.2%), while the unskilled
      occupational group was the most affected occupational group with 35.3% of them
      having SD. Most of the patients with acute bacterial infection died of multiple
      organ failure. CONCLUSION: There is an urgent need to step up public health
      strategies to curtail infections in this environment, encourage better use of the
      existing health facilities by the people, and the government should strive hard
      to make health a top priority.

PMID- 24124383
TI  - Economic evaluation of initial antiretroviral therapy for HIV-infected patients:
      an update of Italian guidelines.
AB  - INTRODUCTION: Highly active antiretroviral therapy (HAART) has allowed many HIV
      infected patients to enjoy longer survival and a better quality of life. We
      performed an economic analysis to estimate the cost-effectiveness of HAART
      regimens in Italy for managing HIV-naive infected patients with a viral load
      below 100,000 copies/mL. PATIENTS AND METHODS: The population considered in the
      model consisted of adult subjects with an HIV viral load below 100,000 copies/mL
      who received antiretroviral HAART treatment for the first time, according to the
      Italian National Guidelines with recommendation grade A1. The incremental cost
      effectiveness analysis of quality-adjusted life years (QALYs) was carried out by
      means of a Markov model. Both the outcomes (QALYs) and the costs were discounted
      by 3.5%. The time horizon adopted in the model was 10 years. The point of view of
      the analysis was that of the Italian national health service. RESULTS: The
      tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) single-tablet regimen (STR)
      (?7,417.00) revealed the lowest mean treatment cost. TDF/FTC + raltegravir (RAL)
      showed a better quality of life (0.906 QALY/year), followed by TDF/FTC/RPV (STR;
      0.900 QALY/year), TDF/FTC + RPV (multipill regimen) (0.889 QALY/year), and
      TDF/FTC + atazanavir (ATV/r) (0.886 QALY/year). TDF/FTC/RPV (STR) appeared to be
      the most cost-effective therapeutic choice (?13,655.00), followed by TDF/FTC +
      RPV (multipill regimen) (?15,803.00), and TDF/FTC + efavirenz (EFV) (?16,181.00).
      The sensitivity analysis on the main variables confirmed the validity of the base
      case scenario. CONCLUSION: STR (TDF/FTC/RPV) is the most cost-effective treatment
      strategy compared with the other therapeutic regimens recommended by the Italian
      guidelines for the treatment of naive patients with a viral load <100,000
      copies/mL. The inclusion of adverse-event management of HIV-infected patients
      affects the cost-effectiveness ratio of all HAART regimens.

PMID- 24124379
TI  - Emerging targets in cancer management: role of the CXCL12/CXCR4 axis.
AB  - The chemokine CXCL12 (SDF-1) and its cell surface receptor CXCR4 were first
      identified as regulators of lymphocyte trafficking to the bone marrow. Soon
      after, the CXCL12/CXCR4 axis was proposed to regulate the trafficking of breast
      cancer cells to sites of metastasis. More recently, it was established that CXCR4
      plays a central role in cancer cell proliferation, invasion, and dissemination in
      the majority of malignant diseases. The stem cell concept of cancer has
      revolutionized the understanding of tumorigenesis and cancer treatment. A growing
      body of evidence indicates that a subset of cancer cells, referred to as cancer
      stem cells (CSCs), plays a critical role in tumor initiation, metastatic
      colonization, and resistance to therapy. Although the signals generated by the
      metastatic niche that regulate CSCs are not yet fully understood, accumulating
      evidence suggests a key role of the CXCL12/CXCR4 axis. In this review we focus on
      physiological functions of the CXCL12/CXCR4 signaling pathway and its role in
      cancer and CSCs, and we discuss the potential for targeting this pathway in
      cancer management. 

PMID- 24124384
TI  - Real-world outcomes of initiating insulin glargine-based treatment versus
      premixed analog insulins among US patients with type 2 diabetes failing oral
      antidiabetic drugs.
AB  - BACKGROUND: In patients with type 2 diabetes mellitus, basal-bolus strategies can
      improve treatment by offering dosing flexibility, and improved satisfaction,
      adherence, and clinical outcomes. The purpose of this study was to compare real
      world outcomes between US patients initiating analog insulin therapy with insulin
      glargine and those initiating with a premixed analog insulin (PMX). METHODS: This
      was a retrospective study of data from patients (>=18 years) with type 2 diabetes
      mellitus in the IMPACT(r) database who initiated insulin treatment with insulin
      glargine (GLA) or a PMX. Clinical and economic outcomes were measured over one
      year, including persistence and adherence, consumption of insulin, glycemic
      outcomes, incident hypoglycemia, and health care resource utilization and cost.
      RESULTS: Data from 2,502 patients were included in the analyses (n = 834 for PMX,
      n = 1,668 for GLA). Compared with PMX, persistence was higher and consumption of
      insulin was lower for GLA (both P < 0.0001). Adherence, glycemic outcomes, and
      hypoglycemia-related events were similar between groups, as were health care
      utilization and total health care costs. Diabetes-related drug and supply costs
      were lower for GLA than for PMX (P < 0.0001 and P = 0.046, respectively).
      CONCLUSION: In US patients with type 2 diabetes mellitus, initiating insulin with
      once-daily GLA, rather than a PMX, is associated with increased treatment
      persistence and similar clinical and hypoglycemic outcomes, but lower diabetes
      pharmacy and supply costs. GLA may be a more flexible option than PMX. However,
      these results also show suboptimal glycemic control in the real-world setting
      despite change in treatment regimens and call for optimization in management of
      patients with type 2 diabetes mellitus.

PMID- 24124385
TI  - Treatment of type 2 diabetes in chronic kidney disease: a case for linagliptin in
      the treatment of diabetes in severe renal impairment.
AB  - Diabetes is the leading cause of chronic kidney disease, and the prevalence of
      both diseases is rising worldwide. Treatment of type 2 diabetes is difficult in
      patients with chronic kidney disease because most oral antidiabetic agents are
      affected by renal function and their use may be contraindicated in this patient
      population. Antidiabetic agents that can be used in patients with type 2 diabetes
      and declining renal function are needed. Incretin-based therapies, such as
      dipeptidyl peptidase-4 inhibitors, are a recent therapeutic class of glucose
      lowering agents that may offer an effective treatment option in patients with
      chronic kidney disease. Within the dipeptidyl peptidase-4 class, linagliptin has
      a unique profile with a primarily nonrenal route of elimination, requiring no
      dose adjustment in patients with chronic kidney disease. This communication
      summarizes the findings of a 1-year, randomized, double-blind, placebo-controlled
      study demonstrating the favorable safety and efficacy profile of linagliptin in
      patients with type 2 diabetes and severe renal impairment. 

PMID- 24124386
TI  - Radiographic evaluation of the effect of obesity on alveolar bone in rats with
      ligature-induced periodontal disease.
AB  - There is evidence that the lack of metabolic control of obese patients may
      accelerate periodontitis. The aim of this study was to evaluate radiographically
      the effect of cafeteria-diet-induced obesity on alveolar bone loss in rats
      subjected to periodontal disease. Twenty male Wistar rats were randomly divided
      into four groups: 1) control group, 2) control and ligature group; 3) cafeteria
      group; and 4) cafeteria and ligature group. The animals were evaluated for
      obesity and euthanized, and the mandible of each rat was removed to perform a
      radiographic evaluation of alveolar bone loss and its effect on diet-induced
      obesity. The results showed greater alveolar bone loss in the mice in Group 4
      (P<0.01). Thus, we concluded that obese mice, on average, showed greater
      radiographic evidence of alveolar bone loss than mice undergoing induction of
      obesity. 

PMID- 24124387
TI  - Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney
      injury in hypertensive disorders of pregnancy.
AB  - Hypertensive disorders of pregnancy (HDP) remain one of the largest single causes
      of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal
      deaths in developed countries. The aim of the study was to evaluate acute kidney
      injury (AKI) in hypertensive disorders of pregnancy and to examine the
      correlation of serum neutrophil gelatinase-associated lipocalin (NGAL) with acute
      kidney injury. This prospective case control study was carried out over a period
      of 1 year. After written, informed consent and ethical clearance, 149 cases of
      hypertensive disorders of pregnancy were screened, and seven were lost to follow
      up. Acute kidney injury was detected in 88 cases and acute renal failure in 30
      cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as
      controls. Quantitative measurement of serum NGAL levels was done by enzyme linked
      immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay
      kit. As per the Kidney Diseases Improving Global Outcomes International
      guidelines acute kidney injury network (AKIN), 50 cases (42.37%) of AKI stage I,
      38 (32.2%) cases of AKI stage II, and 30 (25.42%) cases of renal failure were
      detected. Serum NGAL had a positive association with increasing proteinuria. It
      also had a positive correlation with systolic blood pressure (r~0.36), diastolic
      blood pressure (r~0.37), and serum creatinine (r~0.4). NGAL was found to be
      significantly correlated with creatinine in the cases with the value of the
      correlation coefficient being 0.4. This direct correlation might be a consequence
      of endothelial dysfunction on which hypertension and proteinuria probably
      depends. 

PMID- 24124389
TI  - Why is research fraud wrong?

PMID- 24124388
TI  - Biomarkers for renal transplantation: where are we?
AB  - Although surgical techniques, post-transplant care medicine, and
      immunosuppressants have been greatly improved, permanent acceptance of renal
      allograft remains a clinical challenge owing to the appearance of various
      influencing factors. To predict graft dysfunction, development of noninvasive
      biomarkers is becoming a highlighted research topic in the field of renal
      transplantation, which provides a possibility for physicians to give preemptive
      rescue treatment. From the viewpoint of diagnostic techniques, repetitive
      sampling is prerequisite to identify applicable biomarkers in the clinic. Early
      biomarkers can be used to dynamically monitor renal graft status and accurately
      predict transplant outcome independent of various confounders. This review
      highlights recent studies on the predictive value of biomarkers and methods to
      quantify biomarkers for monitoring kidney transplant. It is important to analyze
      and compare different biomarkers for living, and nonliving donors. Analysis of
      identified clinically relevant biomarkers will advance our understanding of
      distinct molecular and cellular mechanisms of transplantation and provide insight
      into developing novel potential approaches to induce transplant tolerance. 

PMID- 24124390
TI  - Fever of unknown origin successfully treated by oren-gedoku-to (huanglian-jie-du
      tang).
AB  - Oren-gedoku-to is a traditional medicine used for treating inflammatory
      conditions and is given by prescription in Japan, People's Republic of China, and
      Korea. Its anti-inflammatory effect is related to the arachidonate cascade and
      inhibition of cyclo-oxygenase, but research on other anti-inflammatory pathways
      is ongoing. We report a case of fever of unknown origin in a 33-year-old woman.
      The possibility of infection due to human immunodeficiency virus, autoimmune,
      neoplastic, or other disease was examined and excluded. Oren-gedoku-to was
      successfully used to treat her symptoms and may thus be a suitable treatment for
      patients with undiagnosed fever of unknown origin. 

PMID- 24124391
TI  - The prognostic value of ERCC1 and RRM1 gene expression in completely resected non
      small cell lung cancer: tumor recurrence and overall survival.
AB  - BACKGROUND: The roles of excision repair cross-complementing group 1 gene (ERCC1)
      expression and ribonucleotide reductase subunit M1 gene (RRM1) expression in
      completely resected non-small cell lung cancer (NSCLC) are still debatable.
      Previous studies have shown that both genes affected the overall survival and
      outcomes of patients who received platinum-based chemotherapy; however, some
      studies did not show this correlation. The aim of this study was to evaluate the
      prognostic values of ERCC1 and RRM1 gene expression in predicting tumor
      recurrence and overall survival in patients with completely resected NSCLC who
      received adjuvant chemotherapy and in those who did not. PATIENTS AND METHODS: A
      retrospective cohort study was conducted in 247 patients with completely resected
      NSCLC. All patients had been treated with anatomic resection (lobectomy or
      pneumonectomy) with systematic mediastinal lymphadenectomy between January 2002
      and December 2011 at Chiang Mai University Hospital, Chiang Mai, Thailand. They
      were divided into two groups: recurrence and no recurrence. Protein expression of
      ERCC1 and RRM1 was determined by immunohistochemistry. Correlations between
      clinicopathologic variables, including ERCC1 and RRM1 expression and tumor
      recurrence, were analyzed. Univariate and multivariate Cox proportional hazards
      regression analysis stratified by nodal involvement, tumor staging, intratumoral
      blood vessel invasion, intratumoral lymphatic invasion, and tumor necrosis was
      used to identify the prognostic roles of ERCC1 and RRM1. RESULTS: ERCC1 and RRM1
      expression did not demonstrate prognostic value for tumor recurrence and overall
      survival in patients with completely resected NSCLC. In patients who did not
      receive adjuvant chemotherapy treatment, those with high ERCC1 and high RRM1
      expression seemed to have greater potential for tumor recurrence and shorter
      overall survival than did those who had low ERCC1 and low RRM1 (hazard ratio [HR]
      =1.7, 95% confidence interval [CI] =0.6-4.3, P=0.292 and HR =1.6, 95% CI =0.5
      4.5, P=0.411, respectively). In contrast, in patients who received adjuvant
      chemotherapy treatment, those with high ERCC1 and high RRM1 expression seemed to
      have benefited from adjuvant chemotherapy and showed good overall survival
      compared with those who had low ERCC1 and low RRM1 (HR =0.8, 95% CI = 0.4-1.8,
      P=0.612 and HR = 0.4, 95% CI = 0.1-2.4, P=0.325, respectively). Subgroup analysis
      in patients whose first-line metastatic chemotherapy failed demonstrated that
      ERCC1 expression and RRM1 expression were not prognostic factors for tumor
      recurrence and overall survival; however, patients who had high ERCC1 and high
      RRM1 expression seemed to have benefited from first-line chemotherapy treatment
      (HR =0.7, 95% CI =0.3-1.8, P=0.458). CONCLUSION: ERCC1 expression and RRM1
      expression were not prognostic of tumor recurrence and overall survival in
      patients with completely resected NSCLC, either with or without adjuvant
      chemotherapy. Prospective studies that include a larger number of patients are
      needed for definite conclusions.

PMID- 24124392
TI  - Tracking the progress of HIV: the impact of point-of-care tests on antiretroviral
      therapy.
AB  - It is now around 30 years since the discovery of HIV, the virus that causes AIDS.
      More than 70 million people have been infected in that time and around 35 million
      have died. The majority of those currently living with HIV/AIDS are in low- and
      middle-income countries, with sub-Saharan Africa bearing a disproportionate
      burden of the global disease. In high-income countries, the introduction of
      antiretroviral therapy (ART) has drastically reduced the morbidity and mortality
      associated with HIV. Patients on ART are now predicted to have near-normal life
      expectancy and the role of treatment is increasingly recognized in preventing new
      infections. In low- and middle-income countries, treatment is now more widely
      available and around half of those who need ART are currently receiving it. Early
      diagnosis of HIV is essential if ART is to be optimally implemented. Lab-based
      diagnostics for screening, diagnosis, treatment initiation, and the monitoring of
      treatment efficacy are critical in managing the disease and reducing the number
      of new infections each year. The introduction of point-of-care HIV rapid tests
      has transformed the epidemic, particularly in low- and middle-income countries.
      For the first time, these point-of-care tests allow for the rapid identification
      of infected individuals outside the laboratory who can undergo counseling and
      treatment and, in the case of pregnant women, allow the timely initiation of ART
      to reduce the risk of vertical transmission. Although survival is markedly
      improved with ART even in the absence of laboratory monitoring, long-term
      management of people living with HIV on ART, and their partners, is essential to
      ensure successful viral suppression. The burden of disease in many resource-poor
      settings with high HIV prevalence has challenged the ability of local
      laboratories to effectively monitor those on ART. Diagnostics used to initiate
      and monitor treatment are now moving out of the laboratory and into the field.
      These new point-of-care tests for viral load and CD4 are poised to further
      transform the disease and shift the treatment paradigm in low- and middle-income
      countries. 

PMID- 24124393
TI  - Pregnancy outcomes associated with Cesarean deliveries in Peruvian public health
      facilities.
AB  - A continuous rise in the rate of cesarean deliveries has been reported in many
      countries over recent decades. This trend has prompted the emergence of a debate
      on the risks and benefits associated with cesarean section. The present study was
      designed to estimate cesarean section rates over time during the period between
      2000 and 2010 in Peru and to present outcomes for each mode of delivery. This is
      a secondary analysis of a large database obtained from the Perinatal Information
      System, which includes 570,997 pregnant women and their babies from 43 Peruvian
      public health facilities in three geographical regions: coast, highlands, and
      jungle. Over 10 years, 558,901 women delivered 563,668 infants weighing at least
      500 g. The cesarean section rate increased from 25.5% in 2000 to 29.9% in 2010
      (26.9% average; P < 0.01). The rate of stillbirths was lower with cesarean than
      vaginal deliveries (P < 0.01). On the other hand, and as expected, the rates for
      preterm births, twin pregnancies, and preeclampsia were higher in women who
      delivered by cesarean section (P < 0.01). More importantly, the rate of maternal
      mortality was 5.5 times higher in the cesarean section group than in the vaginal
      delivery group. Data suggest that cesarean sections are associated with adverse
      pregnancy outcomes. 

PMID- 24124394
TI  - Excessive gestational weight gain and obesity contribute to altered expression of
      maternal insulin-like growth factor binding protein-3.
AB  - BACKGROUND: Excessive gestational weight gain (GWG) increases risk of large for
      gestational age neonates and subsequent tracking of excess weight throughout the
      life course for both mother and child. Although the physiological mechanisms
      underlying these associations are incomplete, the insulin-like growth factor
      (IGF) axis has garnered attention for its role in fetal growth and development.
      Our purpose was to characterize the IGF axis protein expression patterns in
      mother-infant dyads in respect of excessive GWG. METHODS: WE OBTAINED FASTING
      SERUM SAMPLES AND CORRESPONDING CORD BLOOD FROM EIGHT CONTROLS (ADHERE GROUP: ie,
      those who gained in accordance with 2009 Institute of Medicine GWG
      recommendations) and 13 exceeders (EXCEED group: ie, those who exceeded Institute
      of Medicine GWG recommendations). At study completion, we examined protein
      expression of IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, IGFBP-4, and
      hormone concentrations in both maternal and cord blood. RESULTS: Between-group
      comparisons were made and revealed elevated maternal leptin (P <= 0.05)
      concentrations in gravidas who exceeded recommendations. There was a
      significantly higher number of obese women in the EXCEED group (P < 0.05). After
      adjustment, maternal leptin levels were positively correlated with maternal
      homeostasis model of assessment for insulin resistance score and excessive GWG (P
      <= 0.01). However, serum IGFBP-3 expression in the EXCEED mothers was greater
      than that in the ADHERE group (P <= 0.05). CONCLUSION: These findings provide
      preliminary evidence suggesting that small deviations in IGFBP-regulated IGF
      bioavailability arising from excessive GWG/positive energy balance may affect
      adipocyte differentiation through subclinical insulin resistance.

PMID- 24124395
TI  - Clinical variability of the cerebral autosomal-dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large
      family showing the same mutation.
AB  - A 44-year-old Albanian male was consulted and diagnosed with dementia. His
      magnetic resonance imaging suggested diffuse white matter changes. The suspicion
      of cerebral autosomal-dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a
      suspicion through uncovering a pathogenic mutation at the level of exon 4
      (c.475C>T) of chromosome 19. The patient came from a large family of 13 children,
      all of whom underwent clinical, genetic, and imaging examination. The pathogenic
      mutation was found present only in his eldest sister (50 years old), and she
      presented also very suggestive signs of CADASIL in her respective imaging study,
      but without any clinically significant counterpart. All other siblings were free
      from clinical and radiological signs of the disorder. Our opinion was that we
      were dealing with a mutation showing a very low level of penetrance, with only
      two siblings affected in a large Albanian family with 13 children. 

PMID- 24124396
TI  - Wegener's granulomatosis mimicking inflammatory bowel disease and presenting with
      chronic enteritis.
AB  - Wegener's granulomatosis, also known as anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis, is a small vessel vasculitis with primarily
      pulmonary, renal, and sinus disease manifestations. The prevalence of Wegener's
      granulomatosis is three cases per 100,000 patients. Cardiovascular, neurologic,
      cutaneous, and joint manifestations have been reported in many case reports and
      case series. Gastrointestinal manifestations are less noted in Wegener's
      granulomatosis, although they have been previously reported in the form of
      intestinal perforation and intestinal ischemia. Additionally, there are
      characteristic findings of vasculitis that are noted with active Wegener's
      granulomatosis of the small bowel. We report a case of an elderly patient who
      presented with weight loss, diarrhea, and hematochezia. His symptoms were chronic
      and had lasted for more than 1 year before diagnosis. Inflammatory bowel disease
      or chronic enteritis due to Salmonella arizonae because of reptile exposure
      originally were suspected as etiologies of his presentation. The findings of
      proteinuria, renal failure, and pauci-immune glomerulonephritis on renal biopsy,
      in conjunction with an elevated c-ANCA titer, confirmed the diagnosis of
      Wegener's granulomatosis with associated intestinal vasculitis. This case
      demonstrates an atypical presentation of chronic duodenitis and jejunitis
      secondary to Wegener's granulomatosis, which mimicked inflammatory bowel disease.

PMID- 24124397
TI  - Epithelial cell-adhesion molecule-directed trifunctional antibody immunotherapy
      for symptom management of advanced ovarian cancer.
AB  - Despite advances in cytotoxic chemotherapy and surgical cytoreduction, disease
      recurrence continues to be a troubling problem in patients with advanced-stage
      epithelial ovarian cancer (EOC). Malignant ascites affects approximately 10% of
      patients with recurrent EOC and is associated with troublesome symptoms,
      including abdominal pressure, distension, dyspnea, pelvic pain, and bowel/bladder
      dysfunction. To date, no effective therapy has been identified for the treatment
      of malignant ascites in patients with recurrent, advanced-stage ovarian cancer.
      Recently, immune modulation has gained attention as a novel approach to anti
      cancer therapy. This review explores the role of epithelial cell-adhesion
      molecule (EpCAM)-directed immunotherapy, with a specific focus on the mechanism
      of action of the trifunctional antibody catumaxomab (anti-EpCAM * anti-CD3). In
      addition, clinical trials exploring the use of catumaxomab in the treatment of
      malignant ascites in patients with ovarian cancer are reviewed. 

PMID- 24124399
TI  - Total sleep time obtained from actigraphy versus sleep logs in an academic sleep
      center and impact on further sleep testing.
AB  - BACKGROUND: While actigraphy has been deemed ideal for the longitudinal
      assessment of total sleep time (TST) by select groups, endorsement has not been
      universal and reimbursement is lacking, preventing its widespread use in clinical
      practice. This study compares longitudinal TST data obtained by actigraphy and
      logs preceding a clinical evaluation, and secondarily ascertains whether
      longitudinal TST impacts clinicians' decisions to proceed with further sleep
      testing. METHODS: This was a retrospective, consecutive chart review spanning
      about 4 months in an academic sleep center. Eighty-four patients wore actigraphs
      in anticipation of clinical evaluations. Concomitant completion of sleep logs is
      routinely requested in this setting. Longitudinal TST data available in complete
      form was reviewed in a blinded fashion among a subset of these patients. A review
      of text from clinical notes of an expanded cohort with complete actigraphy data
      (regardless of the degree of completion of logs) enabled determination of the
      frequency and rationale for cancellation of prescheduled sleep testing. RESULTS:
      Of 84 actigraphy recordings, 90% produced complete data, and 30% produced fully
      completed logs. Among the subset with both available in complete form,
      significant mean TST differences were observed on weekends (7.06 +/- 2.18 hours
      versus 8.30 +/- 1.93 hours, P = 0.009), but not on weekdays (7.38 +/- 1.97 hours
      versus 7.72 +/- 1.62 hours, P = 0.450) for actigraphy and logs, respectively.
      Further analyses revealed poor agreement between the two measures, with
      predominantly increased TST estimation with logs. Among those with complete
      actigraphy data (+/-logs), testing was cancelled in 11 (15%), eight of whom (73%)
      presented with hypersomnia and three of whom (27%) presented with insomnia.
      Determination of insufficient sleep time was cited as the primary reason for
      cancellation (64%). CONCLUSION: Actigraphy and sleep logs provided discrepant
      mean TST data on weekends only, and the latter predominantly estimated increased
      TST. Actigraphy was completed more reliably than logs. Longitudinal TST
      information influenced clinicians' decisions to proceed with further testing,
      particularly among patients presenting with hypersomnia.

PMID- 24124398
TI  - Major factors for facilitating change in behavioral strategies to reduce obesity.
AB  - It is very unlikely that our obesity-promoting environment will change in the
      near future. It is therefore mandatory to improve our knowledge of the main
      factors associated with successful adoption of obesity-reducing behaviors. This
      may help design more powerful procedures and strategies to facilitate the
      adoption of healthy lifestyles in a "toxic" environment favoring the development
      of a positive energy balance. The aim of this review is to describe the main
      factors associated with successful adoption of obesity-reducing behaviors and to
      describe the most recent development, limits, and outcomes of lifestyle
      modification programs. The evidence regarding predictors of weight loss and
      weight loss maintenance remains largely incomplete. It is necessary to develop
      strategies matching treatments to patients' needs to improve successful weight
      loss and its maintenance. How to detect and how to address these needs is a
      continuous, challenging, research problem. 

PMID- 24124400
TI  - A train of blue light pulses delivered through closed eyelids suppresses
      melatonin and phase shifts the human circadian system.
AB  - A model of circadian phototransduction was published in 2005 to predict the
      spectral sensitivity of the human circadian system to narrow-band and
      polychromatic light sources by combining responses to light from the spectral
      opponent "blue" versus "yellow" cone bipolar pathway with direct responses to
      light by the intrinsically photosensitive retinal ganglion cells. In the model,
      depolarizing "blue" responses, but not hyperpolarizing "yellow" responses, from
      the "blue" versus "yellow" pathway are combined with the intrinsically
      photosensitive retinal ganglion cell responses. Intrinsically photosensitive
      retinal ganglion cell neurons are known to be much slower to respond to light
      than the cone pathway, so an implication of the model is that periodic flashes of
      "blue" light, but not "yellow" light, would be effective for stimulating the
      circadian system. A within-subjects study was designed to test the implications
      of the model regarding retinal exposures to brief flashes of light. The study was
      also aimed at broadening the foundation for clinical treatment of circadian sleep
      disorders by delivering flashing light through closed eyelids while people were
      asleep. In addition to a dark control night, the eyelids of 16 subjects were
      exposed to three light-stimulus conditions in the phase delay portion of the
      phase response curve while they were asleep: (1) 2-second flashes of 111 W/m(2)
      of blue (lambdamax ~ 480 nm) light once every minute for 1 hour, (2) 131 W/m(2)
      of green (lambdamax ~ 527 nm) light, continuously on for 1 hour, and (3) 2-second
      flashes of the same green light once every minute for 1 hour. Inferential
      statistics showed that the blue flash light-stimulus condition significantly
      delayed circadian phase and significantly suppressed nocturnal melatonin. The
      results of this study further our basic understanding of circadian
      phototransduction and broaden the technical foundations for delivering light
      through closed eyelids during sleep for treating circadian sleep disorders. 

PMID- 24124401
TI  - Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST
      segment elevation myocardial infarction treated with primary percutaneous
      coronary intervention: a network meta-analysis.
AB  - In the absence of head-to-head clinical data, the objective of this study was to
      indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation
      strategy with that of heparin monotherapy in patients with ST-elevation
      myocardial infarction (STEMI) intended for primary percutaneous coronary
      intervention. A systematic literature review was performed to identify randomized
      controlled trials to build a network of bivalirudin and heparin monotherapy
      strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor
      as a common reference strategy. At 30 days, the bivalirudin-based strategy was
      expected to result in lower mortality rates than heparin monotherapy (odds ratio
      [OR], 0.55; credible limit [CrL], 0.32-0.95). This relationship was sustained at
      1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37-2.13), myocardial
      infarction (OR, 0.79; CrL, 0.40-1.55), and thrombolysis in myocardial infarction
      major and minor bleedings (OR, 0.66; CrL, 0.45-0.98) tended to be numerically
      reduced with bivalirudin in comparison with heparin monotherapy. For patients
      with STEMI intended for primary percutaneous coronary intervention, bivalirudin
      is associated with lower mortality rates in comparison with heparin monotherapy.
      This study suggests that bivalirudin is more effective and safer than heparin
      monotherapy and should therefore be preferred over heparin monotherapy. 

PMID- 24124402
TI  - Assessment of Density Functional Methods for Obtaining Geometries at Conical
      Intersections in Organic Molecules.
AB  - A number of commonly available density functionals have been tested for their
      ability to describe the energetics and the geometry at conical intersections in
      connection with the spin-restricted ensemble referenced Kohn-Sham (REKS) method.
      The minimum energy conical intersections have been optimized for several
      molecular systems, which are widely used as paradigmatic models of photochemical
      rearrangements and models of biological chromophores. The results of the
      calculations are analyzed using the sign-change theorem of Longuet-Higgins and a
      method of elementary reaction coordinates of Haas et al. The latter approach
      helps to elucidate the differences between the geometries at conical
      intersections as predicted by the multireference wave function ab initio methods
      and by the density functional methods. Overall, the BH&HLYP density functional
      yields the best results for the conical intersection geometries and energetics.

PMID- 24124403
TI  - One Size Does Not Fit All: The Limits of Structure-Based Models in Drug
      Discovery.
AB  - A major goal in computational chemistry has been to discover the set of rules
      that can accurately predict the binding affinity of any protein-drug complex,
      using only a single snapshot of its three-dimensional structure. Despite the
      continual development of structure-based models, predictive accuracy remains low,
      and the fundamental factors that inhibit the inference of all-encompassing rules
      have yet to be fully explored. Using statistical learning theory and information
      theory, here we prove that even the very best generalized structure-based model
      is inherently limited in its accuracy, and protein-specific models are always
      likely to be better. Our results refute the prevailing assumption that large data
      sets and advanced machine learning techniques will yield accurate, universally
      applicable models. We anticipate that the results will aid the development of
      more robust virtual screening strategies and scoring function error estimations.

PMID- 24124404
TI  - Editor's Introduction to This Issue.

PMID- 24124406
TI  - Bioprospecting potential of the soil metagenome: novel enzymes and bioactivities.
AB  - The microbial diversity in soil ecosystems is higher than in any other microbial
      ecosystem. The majority of soil microorganisms has not been characterized,
      because the dominant members have not been readily culturable on standard
      cultivation media; therefore, the soil ecosystem is a great reservoir for the
      discovery of novel microbial enzymes and bioactivities. The soil metagenome, the
      collective microbial genome, could be cloned and sequenced directly from soils to
      search for novel microbial resources. This review summarizes the microbial
      diversity in soils and the efforts to search for microbial resources from the
      soil metagenome, with more emphasis on the potential of bioprospecting
      metagenomics and recent discoveries. 

PMID- 24124405
TI  - Analytical tools and databases for metagenomics in the next-generation sequencing
      era.
AB  - Metagenomics has become one of the indispensable tools in microbial ecology for
      the last few decades, and a new revolution in metagenomic studies is now about to
      begin, with the help of recent advances of sequencing techniques. The massive
      data production and substantial cost reduction in next-generation sequencing have
      led to the rapid growth of metagenomic research both quantitatively and
      qualitatively. It is evident that metagenomics will be a standard tool for
      studying the diversity and function of microbes in the near future, as
      fingerprinting methods did previously. As the speed of data accumulation is
      accelerating, bioinformatic tools and associated databases for handling those
      datasets have become more urgent and necessary. To facilitate the bioinformatics
      analysis of metagenomic data, we review some recent tools and databases that are
      used widely in this field and give insights into the current challenges and
      future of metagenomics from a bioinformatics perspective. 

PMID- 24124407
TI  - Comparative viral metagenomics of environmental samples from Korea.
AB  - The introduction of metagenomics into the field of virology has facilitated the
      exploration of viral communities in various natural habitats. Understanding the
      viral ecology of a variety of sample types throughout the biosphere is important
      per se, but it also has potential applications in clinical and diagnostic
      virology. However, the procedures used by viral metagenomics may produce
      technical errors, such as amplification bias, while public viral databases are
      very limited, which may hamper the determination of the viral diversity in
      samples. This review considers the current state of viral metagenomics, based on
      examples from Korean viral metagenomic studies-i.e., rice paddy soil, fermented
      foods, human gut, seawater, and the near-surface atmosphere. Viral metagenomics
      has become widespread due to various methodological developments, and much
      attention has been focused on studies that consider the intrinsic role of viruses
      that interact with their hosts. 

PMID- 24124408
TI  - Genome-wide association study of orthostatic hypotension and supine-standing
      blood pressure changes in two korean populations.
AB  - Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic
      blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure
      (dtDBP) between supine and standing, and OH is associated with a failure of the
      cardiovascular reflex to maintain blood pressure on standing from a supine
      position. To understand the underlying genetic factors for OH traits (OH, dtSBP,
      and dtDBP), genome-wide association studies (GWASs) using 333,651 single
      nucleotide polymorphisms (SNPs) were conducted separately for two population
      based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5
      SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the
      Ansung and Ansan cohorts and had p-values of <1 * 10(-5) in the meta-analysis.
      Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value
      criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2,
      and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker
      between cadherin adhesion receptors and the actin cytoskeleton and is essential
      for stabilizing dendritic spines in rodent hippocampal neurons. Although there is
      no report about the function in blood pressure regulation, hippocampal neurons
      interact primarily with the autonomic nervous system and might be related to OH.
      The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and
      rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking,
      STAR intron, and intergenic region, respectively, but there was no clear
      functional link to blood pressure regulation. 

PMID- 24124409
TI  - Gene set analyses of genome-wide association studies on 49 quantitative traits
      measured in a single genetic epidemiology dataset.
AB  - Gene set analysis is a powerful tool for interpreting a genome-wide association
      study result and is gaining popularity these days. Comparison of the gene sets
      obtained for a variety of traits measured from a single genetic epidemiology
      dataset may give insights into the biological mechanisms underlying these traits.
      Based on the previously published single nucleotide polymorphism (SNP) genotype
      data on 8,842 individuals enrolled in the Korea Association Resource project, we
      performed a series of systematic genome-wide association analyses for 49
      quantitative traits of basic epidemiological, anthropometric, or blood chemistry
      parameters. Each analysis result was subjected to subsequent gene set analyses
      based on Gene Ontology (GO) terms using gene set analysis software, GSA-SNP,
      identifying a set of GO terms significantly associated to each trait (pcorr <
      0.05). Pairwise comparison of the traits in terms of the semantic similarity in
      their GO sets revealed surprising cases where phenotypically uncorrelated traits
      showed high similarity in terms of biological pathways. For example, the pH level
      was related to 7 other traits that showed low phenotypic correlations with it. A
      literature survey implies that these traits may be regulated partly by common
      pathways that involve neuronal or nerve systems. 

PMID- 24124410
TI  - Structure and Expression Analyses of SVA Elements in Relation to Functional
      Genes.
AB  - SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided
      into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a
      bioinformatic tool, 22 SVA element-associated genes are identified in the human
      genome. In an analysis of genomic structure, SVA elements are detected in the 5'
      untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH
      (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR
      of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D),
      ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA
      F) genes. They could contribute to exon extension or supplying poly A signals.
      LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed
      alternative transcripts by SVA exonization events. Dominant expression of
      HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous
      expression in various human tissues. Expression of both transcripts (TDRKH_SVA
      and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together,
      these data suggest that SVA elements cause transcript isoforms that contribute to
      modulation of gene regulation in various human tissues. 

PMID- 24124411
TI  - Genome-wide association study of liver enzymes in korean children.
AB  - Liver enzyme elevations, as an indicator of liver function, are widely associated
      with metabolic diseases. Genome-wide population-based association studies have
      identified a genetic susceptibility to liver enzyme elevations and their related
      traits; however, the genetic architecture in childhood remains largely unknown.
      We performed a genome-wide association study to identify new genetic loci for
      liver enzyme levels in a Korean childhood cohort (n = 484). We observed three
      novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated
      with elevated levels of alanine transaminase and aspartate transaminase. Although
      there are some limitations, including genetic power, additional replication and
      functional characterization will support the clarity on the genetic contribution
      that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function. 

PMID- 24124412
TI  - Protein backbone torsion angle-based structure comparison and secondary structure
      database web server.
AB  - Structural information has been a major concern for biological and pharmaceutical
      studies for its intimate relationship to the function of a protein. Three
      dimensional representation of the positions of protein atoms is utilized among
      many structural information repositories that have been published. The
      reliability of the torsional system, which represents the native processes of
      structural change in the structural analysis, was partially proven with previous
      structural alignment studies. Here, a web server providing structural information
      and analysis based on the backbone torsional representation of a protein
      structure is newly introduced. The web server offers functions of secondary
      structure database search, secondary structure calculation, and pair-wise protein
      structure comparison, based on a backbone torsion angle representation system.
      Application of the implementation in pair-wise structural alignment showed highly
      accurate results. The information derived from this web server might be further
      utilized in the field of ab initio protein structure modeling or protein homology
      related analyses. 

PMID- 24124414
TI  - Highly Regioselective Synthesis of Substituted Isoindolinones via Ruthenium
      Catalyzed Alkyne Cyclotrimerizations.
AB  - (Cyclooctadiene)(pentamethylcyclopentadiene)ruthenium chloride [Cp*RuCl(cod)] has
      been used to catalyze the regioselective cyclization of amide-tethered diynes
      with monosubstituted alkynes to give polysubstituted isoindolinones. Notably, the
      presence of a trimethylsilyl group on the diyne generally led to complete control
      over the regioselectivity of the alkyne cyclotrimerization. The cyclization
      reaction worked well in a sustainable non-chlorinated solvent and was tolerant of
      moisture. The optimized conditions were effective with a diverse range of alkynes
      and diynes. The 7-silylisoindolinone products could be halogenated,
      protodesilylated or ring opened to access a range of usefully functionalized
      products.

PMID- 24124415
TI  - Effects of odor on emotion, with implications.
AB  - The sense of smell is found widely in the animal kingdom. Human and animal
      studies show that odor perception is modulated by experience and/or physiological
      state (such as hunger), and that some odors can arouse emotion, and can lead to
      the recall of emotional memories. Further, odors can influence psychological and
      physiological states. Individual odorants are mapped via gene-specified receptors
      to corresponding glomeruli in the olfactory bulb, which directly projects to the
      piriform cortex and the amygdala without a thalamic relay. The odors to which a
      glomerulus responds reflect the chemical structure of the odorant. The piriform
      cortex and the amygdala both project to the orbitofrontal cortex (OFC) which with
      the amygdala is involved in emotion and associative learning, and to the
      entorhinal/hippocampal system which is involved in long-term memory including
      episodic memory. Evidence that some odors can modulate emotion and cognition is
      described, and the possible implications for the treatment of psychological
      problems, for example in reducing the effects of stress, are considered. 

PMID- 24124417
TI  - MOBBED: a computational data infrastructure for handling large collections of
      event-rich time series datasets in MATLAB.
AB  - Experiments to monitor human brain activity during active behavior record a
      variety of modalities (e.g., EEG, eye tracking, motion capture, respiration
      monitoring) and capture a complex environmental context leading to large, event
      rich time series datasets. The considerable variability of responses within and
      among subjects in more realistic behavioral scenarios requires experiments to
      assess many more subjects over longer periods of time. This explosion of data
      requires better computational infrastructure to more systematically explore and
      process these collections. MOBBED is a lightweight, easy-to-use, extensible
      toolkit that allows users to incorporate a computational database into their
      normal MATLAB workflow. Although capable of storing quite general types of
      annotated data, MOBBED is particularly oriented to multichannel time series such
      as EEG that have event streams overlaid with sensor data. MOBBED directly
      supports access to individual events, data frames, and time-stamped feature
      vectors, allowing users to ask questions such as what types of events or features
      co-occur under various experimental conditions. A database provides several
      advantages not available to users who process one dataset at a time from the
      local file system. In addition to archiving primary data in a central place to
      save space and avoid inconsistencies, such a database allows users to manage,
      search, and retrieve events across multiple datasets without reading the entire
      dataset. The database also provides infrastructure for handling more complex
      event patterns that include environmental and contextual conditions. The database
      can also be used as a cache for expensive intermediate results that are reused in
      such activities as cross-validation of machine learning algorithms. MOBBED is
      implemented over PostgreSQL, a widely used open source database, and is freely
      available under the GNU general public license at
      http://visual.cs.utsa.edu/mobbed. Source and issue reports for MOBBED are
      maintained at http://vislab.github.com/MobbedMatlab/ 

PMID- 24124416
TI  - Self-referential processing, rumination, and cortical midline structures in major
      depression.
AB  - Major depression is associated with a bias toward negative emotional processing
      and increased self-focus, i.e., the process by which one engages in self
      referential processing. The increased self-focus in depression is suggested to be
      of a persistent, repetitive and self-critical nature, and is conceptualized as
      ruminative brooding. The role of the medial prefrontal cortex in self-referential
      processing has been previously emphasized in acute major depression. There is
      increasing evidence that self-referential processing as well as the cortical
      midline structures play a major role in the development, course, and treatment
      response of major depressive disorder. However, the links between self
      referential processing, rumination, and the cortical midline structures in
      depression are still poorly understood. Here, we reviewed brain imaging studies
      in depressed patients and healthy subjects that have examined these links. Self
      referential processing in major depression seems associated with abnormally
      increased activity of the anterior cortical midline structures. Abnormal
      interactions between the lateralized task-positive network, and the midline
      cortical structures of the default mode network, as well as the emotional
      response network, may underlie the pervasiveness of ruminative brooding.
      Furthermore, targeting this maladaptive form of rumination and its underlying
      neural correlates may be key for effective treatment. 

PMID- 24124418
TI  - A scientific approach to silent consciousness.

PMID- 24124419
TI  - The paired t-test as a simple latent change score model.

PMID- 24124421
TI  - Nuts consumption and cardiovascular risks.

PMID- 24124422
TI  - Speed of word retrieval in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a common inflammatory - degenerative
      disease of myelin sheet of central nervous system that affects more young people.
      These patients show some degrees of cognition problems such as memory and
      processing disorders. The aim of this study was to evaluate the speed processing
      ability by word finding assessment in three categories include fruits, animals
      and objects in MS patients. MATERIALS AND METHODS: This study carried out as case
      control and descriptive-analytic on 47 MS patients and 29 healthy controls. We
      measured the reaction time (RT) in three stages. Each stage includes 25 words
      (animals, fruits and objects words with high familiarity) that were presented
      randomly. In each stage, the subject should press a key when recognized the
      target category. Collected data analyzed with repeated measure ANOVA, two-way
      ANOVA test, and independent-samples t-test. RESULTS: MS patients in comparison to
      normal healthy subjects show delay in speed of processing in which there was
      significant difference between MS patients and control subjects in mean reaction
      time in all three categories (P < 0.001). CONCLUSION: The speed of processing is
      impaired in MS patients. Consequently, more evaluation and planning treatment
      programs based of speed processing for memory in these patients are necessary for
      them because of the role of memory in daily activities of life.

PMID- 24124420
TI  - Protein change in plant evolution: tracing one thread connecting molecular and
      phenotypic diversity.
AB  - Proteins change over the course of evolutionary time. New protein-coding genes
      and gene families emerge and diversify, ultimately affecting an organism's
      phenotype and interactions with its environment. Here we survey the range of
      structural protein change observed in plants and review the role these changes
      have had in the evolution of plant form and function. Verified examples tying
      evolutionary change in protein structure to phenotypic change remain scarce. We
      will review the existing examples, as well as draw from investigations into
      domestication, and quantitative trait locus (QTL) cloning studies searching for
      the molecular underpinnings of natural variation. The evolutionary significance
      of many cloned QTL has not been assessed, but all the examples identified so far
      have begun to reveal the extent of protein structural diversity tolerated in
      natural systems. This molecular (and phenotypic) diversity could come to
      represent part of natural selection's source material in the adaptive evolution
      of novel traits. Protein structure and function can change in many distinct ways,
      but the changes we identified in studies of natural diversity and protein
      evolution were predicted to fall primarily into one of six categories: altered
      active and binding sites; altered protein-protein interactions; altered domain
      content; altered activity as an activator or repressor; altered protein
      stability; and hypomorphic and hypermorphic alleles. There was also variability
      in the evolutionary scale at which particular changes were observed. Some changes
      were detected at both micro- and macroevolutionary timescales, while others were
      observed primarily at deep or shallow phylogenetic levels. This variation might
      be used to determine the trajectory of future investigations in structural
      molecular evolution. 

PMID- 24124423
TI  - Changes in bone biological markers after treatment of Iranian diabetic patients
      with pioglitazone: No relation to polymorphism of PPAR-gamma (Pro12Ala).
AB  - BACKGROUND: Thiazolidinediones (TZDs) improves insulin sensitivity by activating
      the peroxisome proliferator-activated receptor gamma (PPAR-g). We aimed to study
      any association between variation in bone biochemical markers and single
      nucleotide polymorphism (SNP) in PPAR-gamma (Pro12Ala) and investigate if these
      genetic variants affect bone turnover markers in Iranian diabetic population
      before and after treatment with pioglitazone. MATERIALS AND METHODS: A total of
      101 patients (type 2 diabetic (T2D) were treated for 12 weeks with pioglitazone
      (15 mg/day). Bone Biological markers, osteocalcin, and C-terminal telopeptide of
      type 1 collagen (CTx) were measured before and after pioglitazone therapy. We
      genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala
      polymorphism in PPAR-gamma was done by real-time polymerase chain reaction (RT
      PCR) using TaqMan assay. RESULTS: There were statistically significant
      differences in allele frequencies of Pro12Ala while comparing the controls with
      T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of
      Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of
      assessment of insulin resistance (HOMA-IR) as a maker of insulin resistance was
      significantly decreased (P < 0.001). In respect of bone turnover markers, CTx
      values decreased and osteocalcin significantly increased. (P < 0.001).
      CONCLUSION: Our findings did not reveal a significant association between this
      polymorphism and bone turnover markers after pioglitazone treatment. The reduced
      insulin resistance might be the reason that CTx values decreased and osteocalcin
      increased significantly after short-term pioglitazone treatment. These findings
      suggest the need for further studies on the possible role of insulin in
      regulation of bone metabolism.

PMID- 24124424
TI  - Detection of prognostic factors in metastatic breast cancer.
AB  - BACKGROUND: The aim of this study was to detect prognostic factors in recurrent
      breast cancer metastasis. MATERIALS AND METHODS: This retrospective cohort study
      employed data from 996 breast cancer patients of Isfahan Seyed-o-Shohada research
      center from 1998 to 2010. Stratified Cox proportional hazards model, marginal
      approach, was used to evaluate the prognostic value of estrogen receptor,
      progesterone receptor, tumor protein 53, human epidermal growth factor receptor
      type 2, diagnosis age, nodal ratio, tumor size, antigen Ki67, and cathepsin D.
      Survival curves were plotted using Kaplan-Meier method and log-rank test was
      carried out to compare survival in two categories of nodal ratio (<=0.25 vs.
      >0.25). RESULTS: In simple Cox regression model, age (P = 0.037), nodal ratio (P
      < 0.0001), and Ki67 (P = 0.032) were associated with hazard of distant
      metastasis. Multiple analysis showed that patients with greater nodal ratio had
      significantly higher adjusted hazard of recurrent metastasis (Hazard ratio:
      2.756, 95% Confidence interval: 1.017-7.467; P = 0.046). Tumor size was not an
      independent prognostic factor for recurrent metastasis. Comparing survival
      curves, there was significant difference between two categories of nodal ratio in
      the first (P < 0.0001), second (P < 0.0001) and third (P = 0.024) metastasis;
      survival was higher in-patients with nodal ratio <0.25. CONCLUSION: Our findings
      indicate that tumor size was insignificant; this raises the question about
      conventional premise of being a major prognostic factor for distant metastasis.
      Furthermore, nodal ratio is suggested to clinicians as a prognostic variable in
      follow-up of breast cancer patients; patients with higher nodal ratio have
      greater hazard of distant metastasis.

PMID- 24124425
TI  - Paraoxonase is reduced in patients with growth hormone deficiency: A novel risk
      factor for atherosclerosis.
AB  - BACKGROUND: Growth hormone deficiency (GHD) is associated with an increased
      cardiovascular mortality. Increased oxidative stress has been associated with
      development of cardiovascular and cerebrovascular diseases. In the present study,
      we aimed to evaluate oxidant and antioxidant status in patients with GHD by
      analyzing serum paraoxonase1 (PON1) activity, and malondialdehyde (MDA) and thiol
      levels. MATERIALS AND METHODS: This study was a case-control study. Thirty
      patients with GHD were included in the study and compared with 20 healthy
      controls. Serum PON1 activity, and MDA and thiol levels were measured according
      to an enzymatic spectrophotometric method. RESULTS: Serum MDA levels (2.8 +/- 1.3
      nmol/mL) were higher in GHD group than the controls (1.7 +/- 0.5 nmol/mL) (P =
      0.001). PON1 activity (149.9 +/- 77.9 U/L) was lower in GHD group than the
      controls (286.3 +/- 126.7 U/L) (P = 0.001). Thiol and high-density lipoprotein
      cholesterol (HDL-cholesterol) levels were lower in GHD group (218.6 +/- 103.9
      umol/L and 32.6 +/- 13.4 mg/dL, respectively) than the controls (289.6 +/- 101.1
      umol/L and 54.3 +/- 14.9 mg/dL, respectively) (P = 0.021 and P = 0.001,
      respectively). In GHD patients, serum MDA level was negatively correlated with
      serum HDL-cholesterol (r = -0.499, P = 0.001), and serum PON1 activity was
      positively correlated with serum thiol and HDL-cholesterol levels (r = 0.306, P =
      0.032 and r = 0.303, P = 0.033, respectively). CONCLUSION: These data support
      that GHD is characterized by an imbalance between oxidant and antioxidant
      factors. This abnormality may contribute to the increased atherogenic risk in
      patients with GHD.

PMID- 24124426
TI  - The effect of topiramate on weight loss in patients with type 2 diabetes.
AB  - BACKGROUND: Obesity has been associated with several co-morbidities such as
      diabetes and increased mortality. In general, the use of medication promotes only
      a modest weight loss in the range of 2 to 10 kg, usually most effective during
      the first 6 months of therapy; however, studies have shown positive effects on
      other risk factors such as blood pressure and serum glucose levels, but there are
      fewer studies in patients with diabetes. The aim of this study was to assess the
      effect of topiramate on weight reduction patients with type 2 diabetes. MATERIALS
      AND METHODS: This was a 32-week randomized clinical trial study of 69 subjects
      during 2008-2010. Patients, in two treatment groups were given topiramate (39
      patients) and Placebo (30 patients) and were subjected to participation in a non
      pharmacologic lifestyle intervention program; which were randomly allocated in
      our two groups. The percentage change in body weight and Body Mass Index (BMI) at
      the end of the study was the primary efficacy endpoint and secondary indicators
      were changes in blood pressure (BP), proportion of subjects who achieved 5% or
      10% weight loss, changes in lipid profile (total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides);
      and changes in glycosylated hemoglobin (HgA1c). Paired samples and independent
      samples t-test was used for statistical analysis. (RCT code: IRCT201112036027N2).
      RESULTS: All results were extracted on base of 69 (Intended to treat) ITT
      patients. Mean BMI changes was significantly higher in patients treated with
      topiramate (-1.08 1.90 vs. +0.086 +/- 1.05 kg/m2, P = 0.006). Mean weight loss
      percentage was significantly different between active and placebo groups (-3.02
      +/- 5.78% vs. +0.32 +/- 3.54%, P = 0.005) and systolic blood pressure and HgA1C
      significantly decreased in patients treated with topiramate (P = 0.021 and P =
      0.047, respectively). CONCLUSION: Topiramate induced weight loss and improved
      glycemic control in obese, diabetic patients.

PMID- 24124427
TI  - Ultrasound guided lumbar puncture in emergency department: Time saving and less
      complications.
AB  - BACKGROUND: Lumbar puncture (LP) is an essential procedure in the diagnosis and
      treatment of several critical situations. This procedure is routinely performed
      by palpating external landmarks to find the most appropriate inter-spinous space.
      In the current study, we compared surface landmark and ultrasound (US) guided LP
      in different aspects. MATERIALS AND METHODS: This clinical trial study was
      conducted at the emergency department (ED) of a teaching hospital from March 2009
      to March 2010. Eighty patients were allocated randomly in two equal groups. In
      first group, LP was performed by US-guided method and in the control group by
      palpation of external landmarks of spinal column. Pain score, number of attempts
      for successful dural penetration, numbers of traumatic LP, and procedure time
      were compared between two groups. The performance of US-guided LP was assessed
      with regard to body mass index (BMI) of patients too. RESULTS: The mean of
      procedure time and pain scores were markedly higher in land mark group in
      comparison to US group (6.4 +/- 1.2 and 7.4 +/- 1.1 vs. 3.3 +/- 1.2 and 4.4 +/-
      1.4 respectively). Number of attempts and number of traumatic LPs were
      significantly lower in US group too. In patients with different subgroups of BMI,
      US-guided LP showed better results and less complication when compared with
      surface landmark guided technique. All of these results were statistically
      significant. CONCLUSION: This study showed that US was able to find pertinent
      landmarks to facilitate the LP in patients admitted to ED and resulted in less
      pain and less time wasting. Moreover, patients who have high BMI may benefit more
      than others.

PMID- 24124428
TI  - Effects of multicomponent lifestyle modification on blood pressure control in
      health centers: Design of the study.
AB  - BACKGROUND: Designing an intervention based on healthcare settings resources and
      patient acceptability is potentially important in the prevention of high blood
      pressure(BP) and other risk factors of cardiovascular disease. To explain a
      multicenter randomized controlled trial that is designed to examine the effects
      of the multicomponent lifestyle modification program on BP. MATERIALS AND
      METHODS: The effectiveness of the lifestyle modification program versus usual
      care in health-care centers is evaluated in a randomized controlled trial.
      Patients aged 30years or older having a systolic blood pressure(SBP) of 140
      179mmHg or a diastolic blood pressure(DBP) of 90-109 mm Hg or patients taking
      antihypertensive medications are eligible for the study. -The primary outcomes
      measured are SBP and DBP levels. Mediator outcomes include physical activity
      level, stress scale, dietary composition, and weight measurements. All
      measurements will be conducted after the 4weeks of intervention and also at
      6months. CONCLUSION: Outcomes of the study will present the effects of
      implementing multicomponent lifestyle intervention programs to control BP in
      health-care centers settings.

PMID- 24124429
TI  - Effects of hazelnuts consumption on fasting blood sugar and lipoproteins in
      patients with type 2 diabetes.
AB  - BACKGROUND: Previous studies have demonstrated that nuts consumption have
      beneficial effects on serum lipid profiles in hyperlipidemic or normolipidemic
      subjects. However, similar studies in diabetes field are quite rare. So, we aimed
      to investigate the effects of hazelnut consumption on fasting blood sugar (FBS)
      and lipid profiles in patients with type 2 Diabetes. MATERIALS AND METHODS: An 8
      week controlled randomized parallel study in patients with type 2 diabetes. Fifty
      eligible volunteers were assigned to either the control or intervention groups.
      10% of total daily calorie intake was replaced with hazelnuts in intervention
      group. Blood samples were collected from fasting patients at the start and at the
      end of the study. RESULTS: After 8 weeks, there were significant differences in
      high-density lipoprotein-cholesterol (HDL-C) concentrations between two groups,
      using analyses of covariance (P = 0.009), which was due to the larger HDL-C
      reduction in control group (P = 0.003). Although, Hazelnut group achieved greater
      reduction in triglyceride (TG) concentrations than control group, these changes
      were not statistically significant. Neither between-group changes nor within
      group changes were significant for FBS, total cholesterol (TC), TG, and low
      density lipoprotein-cholesterol (LDL-C) levels. CONCLUSION: Results of this study
      indicated that incorporation of hazelnuts into diet can prevent reduction of HDL
      C concentrations in patients with type 2 diabetes, but had no effect on FBS or
      other lipid profile indices.

PMID- 24124430
TI  - Comparison of blood electrolytes and glucose during cardiopulmonary bypass in
      diabetic and non-diabetic patients.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) during coronary artery bypass grafting
      is thought to contribute significantly to increased blood glucose level and
      altered blood electrolytes balance during the operation. In this (CABG) study,
      blood electrolytes and glucose during CPB in insulin-dependent diabetic and non
      diabetic patients were assessed with special emphasis on the trend of the
      changes. MATERIALS AND METHODS: Blood glucose and electrolytes were assessed in
      30 insulin-dependent diabetic and 30 non-diabetic patients, classified as class
      II and III American Society of Anesthesiologist, before, during, and after CPB.
      Repeated-measures analysis of variance (ANOVA) was used to compare the trend of
      the changes during CPB for the two groups. RESULTS: The trend in blood glucose
      level did not show any significant difference between two groups (P = 0.59). For
      other blood factors, no significant between-group difference was detected except
      for PaCO2 (P = 0.002). CONCLUSION: The study suggested that the changes in blood
      electrolytes and the increase in blood glucose level do not differ between
      insulin dependent diabetic and non-diabetic patients.

PMID- 24124431
TI  - Association of apolipoprotein B, apolipoprotein A, and the its ratio with body
      fat distribution.
AB  - BACKGROUND: To evaluate the association of apolipoprotein B (apoB),
      apolipoprotein A (apoA), and apoB/apoA ratio with the body fat indicators in
      patients with stable angina pectoris (SA). MATERIALS AND METHODS: One hundred and
      twenty two participants aged 40-60 years old, with a mean age of 52.1 +/- 7.2
      years and SA, were recruited for the present study. Body weight, height, and
      waist circumference (WC) were measured, and waist to height ratio (WHtR) was
      calculated. After 12 hours of fasting, a blood sample was obtained and serum
      levels of apoB and apoA were measured and the apoB/apoA ratio was calculated.
      These patients underwent an abdominal computerized tomography scan (CTS) to
      assess visceral and subcutaneous adipose tissue (VAT, SAT). Linear regressions
      were computed to assess the relation of apoB, apoA, and their ratio with various
      measurements of adiposity (VAT, SAT, WC, and WHtR), with adjustment for age, sex,
      and BMI >= 25, WC >= 80 in women and WC >= 90 in men and WHtR >= 0.59. RESULTS:
      From totally 123 patients with SA with a mean age of 52.1 +/- 7.2 years, 44.7%
      male and 55.3% women were entered. Significant positive associations were found
      between visceral fat area and the apoB/apoA ratio (P = 0.02, beta = 0.2), and
      significant negative correlations were observed between visceral fat area and
      apoA concentrations (P = 0.04, beta = -0.2). CONCLUSION: As abdominal fat
      accumulation is associated with other risk factors such as apolipoproteins in
      ischemic patients, then we most focus on control of these factors.

PMID- 24124432
TI  - Reduction of date microbial load with ozone.
AB  - BACKGROUND: Date is one of the foodstuffs that are produced in tropical areas and
      used worldwide. Conventionally, methyl bromide and phosphine are used for date
      disinfection. The toxic side effects of these usual disinfectants have led food
      scientists to consider safer agents such as ozone for disinfection, because food
      safety is a top priority. The present study was performed to investigate the
      possibility of replacing common conventional disinfectants with ozone for date
      disinfection and microbial load reduction. MATERIALS AND METHODS: In this
      experimental study, date samples were ozonized for 3 and 5 hours with 5 and 10
      g/h concentrations and packed. Ozonized samples were divided into two groups and
      kept in an incubator which was maintained at 25 degrees C and 40 degrees C for 9
      months. During this period, every 3 month, microbial load (bacteria, mold, and
      yeast) were examined in ozonized and non-ozonized samples. RESULTS: This study
      showed that ozonization with 5 g/h for 3 hours, 5 g/h for 5 hours, 10 g/h for 3
      hours, and 10 g/h for 5 hours leads to about 25%, 25%, 53%, and 46% reduction in
      date mold and yeast load and about 6%, 9%, 76%, and 74.7% reduction in date
      bacterial load at baseline phase, respectively. Appropriate concentration and
      duration of ozonization for microbial load reduction were 10 g/h and 3 hours.
      CONCLUSION: Date ozonization is an appropriate method for microbial load
      reduction and leads to an increase in the shelf life of dates.

PMID- 24124433
TI  - Prevalence of stomach cancer in Shiraz, Southern Iran.
AB  - BACKGROUND: Worldwide, cancer of stomach is still the fourth common cancer and
      the second cause of mortality among all cancers affecting annually 870,000
      subjects. This study aims to determine the frequency and the characteristics of
      gastric cancer in southern Iran. MATERIALS AND METHODS: 10,800 of all cancers
      registered in Fars Hospital-based Cancer Registry were surveyed among which 574
      cases were gastric cancer in both genders and all age groups. From January 2002
      to December 2007, all hospital-based data were recorded according to
      International Classification of Disease for Oncology (ICD-O) and registered cases
      included all invasive cancers in ICD-10 categories of C-00 to C-80 and all
      duplicate cases were eliminated. RESULTS: Among all registered cancers, there
      were 574 cases of gastric cancer including 69.3% males. The mean age of patients
      was 58.1 +/- 14.8 years, 25.4% with a history of in their first relatives and
      most of them were smokers (50.9%) and from low socioeconomic class (45.5%).
      Metastasis was visible in 182 patients and majority of them underwent surgery
      (64.3%). The majority of gastric cancer patients were older than 50 years,
      smokers, low socioeconomic class, and female in favor of adenocarcinoma.
      CONCLUSION: Our results showed that in our area, treatment programs and health
      plans should focus on men, patients older than 50 years and with adenocarcinoma,
      smokers, and those in a low income level.

PMID- 24124434
TI  - Bone turnover markers in epileptic patients under chronic valproate therapy.
AB  - BACKGROUND: The effects of chronic valproic acid administration on bone health
      have been a matter of concern and controversy. In this study, the bone status
      following valproate intake was assessed by using several bone-related biochemical
      markers. MATERIALS AND METHODS: In this case-control study, 62 epileptic patients
      and 40 age- and gender-matched controls were enrolled. The patients had been
      under chronic valproate therapy (758 +/- 29 mg/day) for at least the past 6
      months, without any vitamin D/or calcium supplementation. Serum markers of bone
      turnover (carboxy-terminal telopeptide of type I collagen (CTX) and bone-specific
      alkaline phosphatase [BALP]), calcium, phosphorus, total alkaline phosphatase,
      and parathyroid hormone levels were measured in both groups. RESULTS: The markers
      of bone turnover as well as other measured bone biochemical parameters did not
      statistically differ between the two groups. CONCLUSION: Valproate therapy at the
      mentioned doses does not seem to change bone turnover in adult epileptic
      patients.

PMID- 24124435
TI  - Gender inequality and bio-social factors in nutritional status among under five
      children attending anganwadis in an urban slum of a town in Western Maharashtra,
      India.
AB  - Nutrition for under-5 children is of great importance as the foundation for life
      time health, strength, and intellectual vitality is laid during this period.
      Globally, more than one-third of the child deaths are attributable to under
      nutrition. The discriminatory attitudes against female children vary from being
      implicit to those that are quite explicit. So, the present cross-sectional study
      aims to assess the nutritional status (gender differences) of 146 under-5
      children attending Anganwadis and also to study the bio-socio-demographic factors
      associated with malnutrition attending three Anganwadis of Adopted Urban slum
      area, involving anthropometric examination using standardized techniques and
      interview using predesigned semi-structured questionnaire for the mothers in
      September-October 2011. Nutritional status grading was done based on weight for
      age as per Indian Academy of Pediatrics (IAP) Classification and using height for
      age as per Vishveshwara Rao's Classification. 51.4% were males, majority in age
      group of 2-3 years. 63% children were malnourished, majority in Grade I
      malnutrition. Out of the total females, 72% were stunted and 43% were severely
      malnourished having mid arm circumference <12.5 cm. Birth order (P < 0.05),
      education status of the mother (P < 0.001), socio-economic status (P < 0.05) and
      type of family (P < 0.05) were found to be significantly associated with
      malnutrition. 

PMID- 24124437
TI  - Multiple intracranial dural arteriovenous fistula.
AB  - Dural arteriovenous fistula (DAVF) is also known as dural arteriovenous
      malformation. Two forms of DAVF have been introduced, however, here we present an
      exceptional case of DAVF with unique origin and drainage. In this study, we
      present a rare case of multiple DAVFs in a 50 year old man with right parietal
      intraparenchymal hemorrhage. MRI showed two round right parieto-occipital masses
      with flow void intensity adjacent to superior sagittal sinus (SSS). Another
      pathology connected to SSS by an abnormal cortical vein was detected anterior to
      first lesion. This study showed that both DAVFs were simultaneously drained in
      SSS in our patient. 

PMID- 24124436
TI  - Can health promotion model constructs predict nutritional behavior among diabetic
      patients?
AB  - Since, the nutritional behavior is a complicated process in which various factors
      play the role, this study aimed at specifying the effective factors in
      nutritional behavior of diabetic patients based on Health Promotion Model. This
      paper reviews the published articles from 2000 to the beginning of 2012, using
      the various data banks and search engines such as PubMed, ProQuest, Scopus,
      Elsevier, and the key words" perceived benefits and barriers, perceived self
      efficacy, social support, activity related affect, situational influences,
      commitment to plan of action, immediate competing demands and diabetes, self
      caring and diabetes. Unfavorable self-care situation especially, inappropriate
      nutritional behavior is related to some effective modifiable factors. Perceived
      benefits and self-efficacy regarding behaviors play a major role in the
      nutritional behaviors. Social support especially, spouses' support has a
      significant role in this regard. Moreover, there is a reverse relationship
      between perceived barriers and nutritional self-care. In addition, behavioral
      feelings, situational influences, commitment to plan of action and immediate
      competing demands and preferences can also impact and overshadow the nutritional
      self-care. Following the relationship between constructs of Health Promotion
      Model and nutritional behavior the constructs of this model can be utilized as
      the basis for educational intervention among diabetes. 

PMID- 24124438
TI  - Identification of homogeneously staining regions in leukemia patients.
AB  - Homogeneously staining regions (HSR) or double minute chromosomes (dmin) are
      autonomously replicating extra-chromosomal elements that are frequently
      associated with gene amplification in a variety of cancers. The diagnosis of
      leukemia patients was based on characterization of the leukemic cells obtained
      from bone marrow cytogenetics. This study report two cases, one with Acute
      Myeloblastic Leukemia without maturation (AML-M1), aged 23-year-old female, and
      the other with chronic myelogenous leukemia (CML)-blast crisis, a 28-year-old
      female associated with double minute chromosomes. Most cases of acute myeloid
      leukemia with dmin in the literature (including our cases) have been diagnosed as
      having acute myeloid leukemia. 

PMID- 24124439
TI  - Changes in bone biological markers after treatment of Iranian diabetic patients
      with pioglitazone: No relation to polymorphism of PPAR-gamma (Pro12Ala).

PMID- 24124440
TI  - Pegylated interferon/telbivudine sequential therapy in Hepatitis Be antigen
      negative severe chronic hepatitis B patient.

PMID- 24124444
TI  - A Ham1p-dependent mechanism and modulation of the pyrimidine biosynthetic pathway
      can both confer resistance to 5-fluorouracil in yeast.
AB  - 5-Fluorouracil (5-FU) is an anticancer drug and pyrimidine analogue. A problem in
      5-FU therapy is acquired resistance to the drug. To find out more about the
      mechanisms of resistance, we screened a plasmid library in yeast for genes that
      confer 5-FU resistance when overexpressed. We cloned five genes: CPA1, CPA2,
      HMS1, HAM1 and YJL055W. CPA1 and CPA2 encode a carbamoyl phosphate synthase
      involved in arginine biosynthesis and HMS1 a helix-loop-helix transcription
      factor. Our results suggest that CPA1, CPA2, and HMS1 confer 5-FU resistance by
      stimulating pyrimidine biosynthesis. Thus, they are unable to confer 5-FU
      resistance in a ura2 mutant, and inhibit the uptake and incorporation into RNA of
      both uracil and 5-FU. In contrast, HAM1 and YJL055W confer 5-FU resistance in a
      ura2 mutant, and selectively inhibit incorporation into RNA of 5-FU but not
      uracil. HAM1 is the strongest resistance gene, but it partially depends on
      YJL055W for its function. This suggests that HAM1 and YJL055W function together
      in mediating resistance to 5-FU. Ham1p encodes an inosine triphosphate
      pyrophosphatase that has been implicated in resistance to purine analogues. Our
      results suggest that Ham1p could have a broader specificity that includes 5-FUTP
      and other pyrimidine analogoue triphosphates.

PMID- 24124445
TI  - Dephytinisation with intrinsic wheat phytase and iron fortification significantly
      increase iron absorption from fonio (Digitaria exilis) meals in West African
      women.
AB  - Low iron and high phytic acid content make fonio based meals a poor source of
      bioavailable iron. Phytic acid degradation in fonio porridge using whole grain
      cereals as phytase source and effect on iron bioavailability when added to iron
      fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali
      markets were screened for phytic acid and phytase activity. We performed an iron
      absorption study in Beninese women (n = 16), using non-dephytinised fonio
      porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each
      fortified with (57)Fe or (58)Fe labeled FeSO4. Iron absorption was quantified by
      measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid
      varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds
      values higher than grains and nuts. Phytase activity ranged from 0.17+/-1.61
      (fonio) to 2.9+/-1.3 phytase unit (PU) per g (whole wheat). Phytic acid was
      almost completely degraded in FWFP after 60 min of incubation (pH~5.0, 50 degrees
      C). Phytate?iron molar ratios decreased from 23.7?1 in FFP to 2.7?1 in FWFP. Iron
      fortification further reduced phytate?iron molar ratio to 1.9?1 in FFP and 0.3?1
      in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly
      increased from 2.6% (0.8-7.8) in FFP to 8.3% (3.8-17.9) in FWFP (P<0.0001).
      Dephytinisation of fonio porridge with intrinsic wheat phytase increased
      fractional iron absorption 3.2 times, suggesting it could be a possible strategy
      to decrease PA in cereal-based porridges. 

PMID- 24124446
TI  - Resource pulses in desert river habitats: productivity-biodiversity hotspots, or
      mirages?
AB  - Resource pulses in the world's hot deserts are driven largely by rainfall and are
      highly variable in both time and space. However, run-on areas and drainage lines
      in arid regions receive more water more often than adjacent habitats, and
      frequently sustain relatively high levels of primary productivity. These
      landscape features therefore may support higher biotic diversity than other
      habitats, and potentially act as refuges for desert vertebrates and other biota
      during droughts. We used the ephemeral Field River in the Simpson Desert, central
      Australia, as a case study to quantify how resources and habitat characteristics
      vary spatially and temporally along the riparian corridor. Levels of moisture and
      nutrients were greater in the clay-dominated soils of the riverine corridor than
      in the surrounding sand dunes, as were cover values of trees, annual grasses,
      other annual plants and litter; these resources and habitat features were also
      greater near the main catchment area than in the distal reaches where the river
      channel runs out into extensive dune fields. These observations confirm that the
      riverine corridor is more productive than the surrounding desert, and support the
      idea that it may act as a refuge or as a channel for the ingress of peri-desert
      species. However, the work also demonstrates that species diversity of
      invertebrates and plants is not higher within the river corridor; rather, it is
      driven by rainfall and the accompanying increase in annual plants following a
      rain event. Further research is required to identify the biota that depend upon
      these resource pulses. 

PMID- 24124447
TI  - Efficacy of a food safety comic book on knowledge and self-reported behavior for
      persons living with AIDS.
AB  - INTRODUCTION: Persons living with AIDS are highly vulnerable to foodborne enteric
      infections with the potential for substantial morbidity and mortality.
      Educational materials about foodborne enteric infections intended for this
      immunocompromised population have not been assessed for their efficacy in
      improving knowledge or encouraging behavior change. METHODS/RESULTS: AIDS
      patients in four healthcare facilities in Chicago, New Orleans, and Puerto Rico
      were recruited using fliers and word of mouth to healthcare providers. Those who
      contacted research staff were interviewed to determine food safety knowledge gaps
      and risky behaviors. A food safety educational comic book that targeted knowledge
      gaps was created, piloted, and provided to these patients who were instructed to
      read it and return at least 2 weeks later for a follow-up interview. The overall
      food safety score was determined by the number of the 26
      knowledge/belief/behavior questions from the survey answered correctly. Among 150
      patients who participated in both the baseline and follow-up questionnaire, the
      intervention resulted in a substantial increase in the food safety score
      (baseline 59%, post-intervention 81%, p<0.001). The intervention produced a
      significant increase in all the food safety knowledge, belief, and behavior items
      that comprised the food safety score. Many of these increases were from baseline
      knowledge below 80 percent to well above 90%. Most (85%) of the patients stated
      they made a change to their behavior since receiving the educational booklet.
      CONCLUSION: This comic book format intervention to educate persons living with
      AIDS was highly effective. Future studies should examine to what extent long-term
      behavioral changes result.

PMID- 24124448
TI  - Cytoskeletal protein translation and expression in the rat brain are stressor
      dependent and region-specific.
AB  - Stress is an integral component of life that can sometimes cause a critical
      overload, depending on the qualitative and quantitative natures of the stressors.
      The involvement of actin, the predominant component of dendritic integrity, is a
      plausible candidate factor in stress-induced neuronal cytoskeletal changes. The
      major aim of this study was to compare the effects of three different stress
      conditions on the transcription and translation of actin-related cytoskeletal
      genes in the rat brain. Male Wistar rats were exposed to one or other of the
      frequently used models of physical stress, i.e. electric foot shock stress
      (EFSS), forced swimming stress (FSS), or psychosocial stress (PSS) for periods of
      3, 7, 14, or 21 days. The relative mRNA and protein expressions of beta-actin,
      cofilin and mitogen-activated protein kinase 1 (MAPK-1) were determined by qRT-
      PCR and western blotting from hippocampus and frontal cortex samples. Stressor
      specific alterations in both beta-actin and cofilin expression levels were seen
      after stress. These alterations were most pronounced in response to EFSS, and
      exhibited a U-shaped time course. FSS led to a significant beta-actin mRNA
      expression elevation in the hippocampus and the frontal cortex after 3 and 7
      days, respectively, without any subsequent change. PSS did not cause any change
      in beta-actin or cofilin mRNA or protein expression in the examined brain
      regions. EFSS, FSS and PSS had no effect on the expression of MAPK-1 mRNA at any
      tested time point. These findings indicate a very delicate, stress type-dependent
      regulation of neuronal cytoskeletal components in the rat hippocampus and frontal
      cortex. 

PMID- 24124449
TI  - Support measures to estimate the reliability of evolutionary events predicted by
      reconciliation methods.
AB  - The genome content of extant species is derived from that of ancestral genomes,
      distorted by evolutionary events such as gene duplications, transfers and losses.
      Reconciliation methods aim at recovering such events and at localizing them in
      the species history, by comparing gene family trees to species trees. These
      methods play an important role in studying genome evolution as well as in
      inferring orthology relationships. A major issue with reconciliation methods is
      that the reliability of predicted evolutionary events may be questioned for
      various reasons: Firstly, there may be multiple equally optimal reconciliations
      for a given species tree-gene tree pair. Secondly, reconciliation methods can be
      misled by inaccurate gene or species trees. Thirdly, predicted events may
      fluctuate with method parameters such as the cost or rate of elementary events.
      For all of these reasons, confidence values for predicted evolutionary events are
      sorely needed. It was recently suggested that the frequency of each event in the
      set of all optimal reconciliations could be used as a support measure. We put
      this proposition to the test here and also consider a variant where the support
      measure is obtained by additionally accounting for suboptimal reconciliations.
      Experiments on simulated data show the relevance of event supports computed by
      both methods, while resorting to suboptimal sampling was shown to be more
      effective. Unfortunately, we also show that, unlike the majority-rule consensus
      tree for phylogenies, there is no guarantee that a single reconciliation can
      contain all events having above 50% support. In this paper, we detail how to rely
      on the reconciliation graph to efficiently identify the median reconciliation.
      Such median reconciliation can be found in polynomial time within the potentially
      exponential set of most parsimonious reconciliations. 

PMID- 24124450
TI  - Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration
      and invasion of epithelial ovarian carcinoma cells.
AB  - Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed
      in post-chemotherapy (CT) primary cultures derived from serous epithelial ovarian
      cancer (EOC) patients, when compared to primary cultures derived from matched
      primary (prior to CT) tumors. However, we found no differences in the RUNX2
      methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA
      methylation-based epigenetic mechanisms have no impact on RUNX2 expression in
      advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed
      significantly higher expression not only in metastatic tissue, but also in high
      grade primary tumors and even in low malignant potential tumors. Knockdown of the
      RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and
      significantly inhibited EOC cell migration and invasion. Gene expression
      profiling and consecutive network and pathway analyses confirmed these findings,
      as various genes and pathways known previously to be implicated in ovarian
      tumorigenesis, including EOC tumor invasion and metastasis, were found to be
      downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and
      some EOC tumor suppressor genes were induced. Taken together, our data are
      indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC
      progression and suggest that RUNX2 might be a novel EOC therapeutic target.
      Further studies are needed to more completely elucidate the functional
      implications of RUNX2 and other members of the RUNX gene family in ovarian
      tumorigenesis. 

PMID- 24124451
TI  - Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after
      vaccination of HIV infected individuals.
AB  - BACKGROUND: HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV
      immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL)
      has proven immunogenic and effective in reducing viral loads in multiple pigtail
      macaque studies, warranting clinical evaluation. METHODOLOGY: We performed a
      phase I, single centre, placebo-controlled, double-blinded and dose-escalating
      study to evaluate the safety and preliminary immunogenicity of a novel
      therapeutic vaccine approach 'OPAL-HIV-Gag(c)'. This vaccine is comprised of 120
      15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade
      sequence proteome, pulsed on white blood cells enriched from whole blood using a
      closed system, followed by intravenous reinfusion. Patients with undetectable HIV
      viral loads (<50 copies/ml plasma) on HAART received four administrations at week
      0, 4, 8 and 12, and were followed up for 12 weeks post-treatment. Twenty-three
      people were enrolled in four groups: 12 mg (n = 6), 24 mg (n = 7), 48 mg (n = 2)
      or matching placebo (n = 8) with 18 immunologically evaluable. T-cell
      immunogenicity was assessed by IFNgamma ELIspot and intracellular cytokine
      staining (ICS). RESULTS: The OPAL-HIV-Gag(c) peptides were antigenic in vitro in
      17/17 subjects. After vaccination with OPAL-HIV-Gag(c), 1/6 subjects at 12 mg and
      1/6 subjects at 24 mg dose groups had a 2- and 3-fold increase in ELIspot
      magnitudes from baseline, respectively, of Gag-specific CD8+ T-cells at week 14,
      compared to 0/6 subjects in the placebo group. No Gag-specific CD4+ T-cell
      responses or overall change in Rev, Nef, Tat and CMV specific responses were
      detected. Marked, transient and self-limiting lymphopenia was observed
      immediately post-vaccination (4 hours) in OPAL-HIV-Gag(c) but not in placebo
      recipients, with median fall from 1.72 to 0.67 million lymphocytes/mL for active
      groups (P<0.001), compared to post-placebo from 1.70 to 1.56 lymphocytes/ml (P =
      0.16). CONCLUSION/SIGNIFICANCE: Despite strong immunogenicity observed in several
      Macaca nemestrina studies using this approach, OPAL-HIV-Gag(c) was not
      significantly immunogenic in humans and improved methods of generating high
      frequency Gag-specific T-cell responses are required. NAME OF REGISTRY:
      ClinicalTrials.gov, Registry number: NCT01123915, URL trial registry database:
      http://www.clinicaltrials.gov/ct2/results?term=OPAL-HIV-1001&Search=Search.

PMID- 24124452
TI  - The size of endotracheal tube and sore throat after surgery: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Recent studies showed that sore throat following endotracheal
      intubation was a common problem following surgery. The objective of this
      systematic review and meta-analysis of published randomized controlled trials
      (RCTs) or cohort studies was to estimate whether the size of endotracheal tube
      (ETT) affects the incidence of postoperative sore throat (POST) after general
      anesthesia. METHODS: The following databases were searched electronically: PubMed
      (updated to Dec 2012), EMBASE (updated to 15 Dec 2012), Google scholar, World
      Health Organization International Clinical Trials Registry Platform (Jul 2011),
      Chinese BioMedical Literature Database (1978 to Jul 2011), and China National
      Knowledge Infrastructure (1994 to Jul 2011). Studies comparing the size of
      endotracheal tube for elective surgery were included. RESULTS: Three trials with
      a total of 509 female patients were included in the current analysis. The size of
      ETT used were 6.0 mm and 7.0 mm. Pooled studies from these trials showed that the
      smaller size of ETT (6.0 mm) significantly decreased the incidence of POST in
      post-anesthesia care unit (PACU) (RR = 0.56, 95% CI 0.42-0.75, P<0.01) and at 24
      h after surgery (RR = 0.69, 95% CI 0.48-0.99, P<0.05). A smaller size of ETT (6.0
      mm) was associated with a lower incidence of PH in PACU (RR = 0.69, 95% CI 0.55
      0.87, P<0.01), but did not affect the incidence of PH at 24 h after surgery (RR =
      0.73, 95% CI 0.46-1.15, P>0.05). CONCLUSION: Our meta-analysis suggests that
      patients under general anesthesia with a smaller size of ETT (6.0 mm) were
      associated with a lower incidence of POST in female patients. More studies with
      adequate numbers of patients were warranted to evaluate other size of ETT on the
      incidence of PH and POST after general surgery among different populations.

PMID- 24124453
TI  - NF-kappaB is activated in CD4+ iNKT cells by sickle cell disease and mediates
      rapid induction of adenosine A2A receptors.
AB  - Reperfusion injury following tissue ischemia occurs as a consequence of vaso
      occlusion that is initiated by activation of invariant natural killer T (iNKT)
      cells. Sickle cell disease (SDC) results in widely disseminated microvascular
      ischemia and reperfusion injury as a result of vaso-occlusion by rigid and
      adhesive sickle red blood cells. In mice, iNKT cell activation requires NF-kappaB
      signaling and can be inhibited by the activation of anti-inflammatory adenosine
      A2A receptors (A2ARs). Human iNKT cells are divided into subsets of CD4+ and CD4-
      cells. In this study we found that human CD4+ iNKT cells, but not CD4- cells
      undergo rapid NF-kappaB activation (phosphorylation of NF-kappaB on p65) and
      induction of A2ARs (detected with a monoclonal antibody 7F6-G5-A2) during SCD
      painful vaso-occlusive crises. These findings indicate that SCD primarily
      activates the CD4+ subset of iNKT cells. Activation of NF-kappaB and induction of
      A2ARs is concordant, i.e. only CD4+ iNKT cells with activated NF-kappaB expressed
      high levels of A2ARs. iNKT cells that are not activated during pVOC express low
      levels of A2AR immunoreactivity. These finding suggest that A2AR transcription
      may be induced in CD4+ iNKT cells as a result of NF-kappaB activation in SCD. In
      order to test this hypothesis further we examined cultured human iNKT cells. In
      cultured cells, blockade of NF-kappaB with Bay 11-7082 or IKK inhibitor VII
      prevented rapid induction of A2AR mRNA and protein upon iNKT activation. In
      conclusion, NF-kappaB-mediated induction of A2ARs in iNKT cells may serve as a
      counter-regulatory mechanism to limit the extent and duration of inflammatory
      immune responses. As activated iNKT cells express high levels of A2ARs following
      their activation, they may become highly sensitive to inhibition by A2AR
      agonists. 

PMID- 24124454
TI  - Extraction of high quality DNA from seized Moroccan cannabis resin (Hashish).
AB  - The extraction and purification of nucleic acids is the first step in most
      molecular biology analysis techniques. The objective of this work is to obtain
      highly purified nucleic acids derived from Cannabis sativa resin seizure in order
      to conduct a DNA typing method for the individualization of cannabis resin
      samples. To obtain highly purified nucleic acids from cannabis resin (Hashish)
      free from contaminants that cause inhibition of PCR reaction, we have tested two
      protocols: the CTAB protocol of Wagner and a CTAB protocol described by Somma
      (2004) adapted for difficult matrix. We obtained high quality genomic DNA from 8
      cannabis resin seizures using the adapted protocol. DNA extracted by the Wagner
      CTAB protocol failed to give polymerase chain reaction (PCR) amplification of
      tetrahydrocannabinolic acid (THCA) synthase coding gene. However, the extracted
      DNA by the second protocol permits amplification of THCA synthase coding gene
      using different sets of primers as assessed by PCR. We describe here for the
      first time the possibility of DNA extraction from (Hashish) resin derived from
      Cannabis sativa. This allows the use of DNA molecular tests under special
      forensic circumstances. 

PMID- 24124456
TI  - Four theorems on the psychometric function.
AB  - In a 2-alternative forced-choice (2AFC) discrimination task, observers choose
      which of two stimuli has the higher value. The psychometric function for this
      task gives the probability of a correct response for a given stimulus difference,
      Deltax. This paper proves four theorems about the psychometric function. Assuming
      the observer applies a transducer and adds noise, Theorem 1 derives a convenient
      general expression for the psychometric function. Discrimination data are often
      fitted with a Weibull function. Theorem 2 proves that the Weibull "slope"
      parameter, beta, can be approximated by beta(Noise) x beta(Transducer), where
      beta(Noise) is the beta of the Weibull function that fits best to the cumulative
      noise distribution, and beta(Transducer) depends on the transducer. We derive
      general expressions for beta(Noise) and beta(Transducer), from which we derive
      expressions for specific cases. One case that follows naturally from our general
      analysis is Pelli's finding that, when d' ? (Deltax)(b), beta ~ beta(Noise) x b.
      We also consider two limiting cases. Theorem 3 proves that, as sensitivity
      improves, 2AFC performance will usually approach that for a linear transducer,
      whatever the actual transducer; we show that this does not apply at signal levels
      where the transducer gradient is zero, which explains why it does not apply to
      contrast detection. Theorem 4 proves that, when the exponent of a power-function
      transducer approaches zero, 2AFC performance approaches that of a logarithmic
      transducer. We show that the power-function exponents of 0.4-0.5 fitted to
      suprathreshold contrast discrimination data are close enough to zero for the
      fitted psychometric function to be practically indistinguishable from that of a
      log transducer. Finally, Weibull beta reflects the shape of the noise
      distribution, and we used our results to assess the recent claim that internal
      noise has higher kurtosis than a Gaussian. Our analysis of beta for contrast
      discrimination suggests that, if internal noise is stimulus-independent, it has
      lower kurtosis than a Gaussian.

PMID- 24124455
TI  - Trauma history and depression predict incomplete adherence to antiretroviral
      therapies in a low income country.
AB  - BACKGROUND: As antiretroviral therapy (ART) for HIV becomes increasingly
      available in low and middle income countries (LMICs), understanding reasons for
      lack of adherence is critical to stemming the tide of infections and improving
      health. Understanding the effect of psychosocial experiences and mental health
      symptomatology on ART adherence can help maximize the benefit of expanded ART
      programs by indicating types of services, which could be offered in combination
      with HIV care. METHODOLOGY: The Coping with HIV/AIDS in Tanzania (CHAT) study is
      a longitudinal cohort study in the Kilimanjaro Region that included randomly
      selected HIV-infected (HIV+) participants from two local hospital-based HIV
      clinics and four free-standing voluntary HIV counselling and testing sites.
      Baseline data were collected in 2008 and 2009; this paper used data from 36 month
      follow-up interviews (N = 468). Regression analyses were used to predict factors
      associated with incomplete self-reported adherence to ART. RESULTS: Incomplete
      art adherence was significantly more likely to be reported amongst participants
      who experienced a greater number of childhood traumatic events: sexual abuse
      prior to puberty and the death in childhood of an immediate family member not
      from suicide or homicide were significantly more likely in the non-adherent group
      and other negative childhood events trended toward being more likely. Those with
      incomplete adherence had higher depressive symptom severity and post-traumatic
      stress disorder (PTSD). In multivariable analyses, childhood trauma, depression,
      and financial sacrifice remained associated with incomplete adherence.
      DISCUSSION: This is the first study to examine the effect of childhood trauma,
      depression and PTSD on HIV medication adherence in a low income country facing a
      significant burden of HIV. Allocating spending on HIV/AIDS toward integrating
      mental health services with HIV care is essential to the creation of systems that
      enhance medication adherence and maximize the potential of expanded
      antiretroviral access to improve health and reduce new infections.

PMID- 24124457
TI  - CEQer: a graphical tool for copy number and allelic imbalance detection from
      whole-exome sequencing data.
AB  - Copy number alterations (CNA) are common events occurring in leukaemias and solid
      tumors. Comparative Genome Hybridization (CGH) is actually the gold standard
      technique to analyze CNAs; however, CGH analysis requires dedicated instruments
      and is able to perform only low resolution Loss of Heterozygosity (LOH) analyses.
      Here we present CEQer (Comparative Exome Quantification analyzer), a new
      graphical, event-driven tool for CNA/allelic-imbalance (AI) coupled analysis of
      exome sequencing data. By using case-control matched exome data, CEQer performs a
      comparative digital exonic quantification to generate CNA data and couples this
      information with exome-wide LOH and allelic imbalance detection. This data is
      used to build mixed statistical/heuristic models allowing the identification of
      CNA/AI events. To test our tool, we initially used in silico generated data, then
      we performed whole-exome sequencing from 20 leukemic specimens and corresponding
      matched controls and we analyzed the results using CEQer. Taken globally, these
      analyses showed that the combined use of comparative digital exon quantification
      and LOH/AI allows generating very accurate CNA data. Therefore, we propose CEQer
      as an efficient, robust and user-friendly graphical tool for the identification
      of CNA/AI in the context of whole-exome sequencing data. 

PMID- 24124458
TI  - HIV and the risk of direct obstetric complications: a systematic review and meta
      analysis.
AB  - BACKGROUND: Women of reproductive age in parts of sub-Saharan Africa are faced
      both with high levels of HIV and the threat of dying from the direct
      complications of pregnancy. Clinicians practicing in such settings have reported
      a high incidence of direct obstetric complications among HIV-infected women, but
      the evidence supporting this is unclear. The aim of this systematic review is to
      establish whether HIV-infected women are at increased risk of direct obstetric
      complications. METHODS AND FINDINGS: Studies comparing the frequency of obstetric
      haemorrhage, hypertensive disorders of pregnancy, dystocia and intrauterine
      infections in HIV-infected and uninfected women were identified. Summary
      estimates of the odds ratio (OR) for the association between HIV and each
      obstetric complication were calculated through meta-analyses. In total, 44
      studies were included providing 66 data sets; 17 on haemorrhage, 19 on
      hypertensive disorders, five on dystocia and 25 on intrauterine infections. Meta
      analysis of the OR from studies including vaginal deliveries indicated that HIV
      infected women had over three times the risk of a puerperal sepsis compared with
      HIV-uninfected women [pooled OR: 3.43, 95% confidence interval (CI): 2.00-5.85];
      this figure increased to nearly six amongst studies only including women who
      delivered by caesarean (pooled OR: 5.81, 95% CI: 2.42-13.97). For other obstetric
      complications the evidence was weak and inconsistent. CONCLUSIONS: The higher
      risk of intrauterine infections in HIV-infected pregnant and postpartum women may
      require targeted strategies involving the prophylactic use of antibiotics during
      labour. However, as the huge excess of pregnancy-related mortality in HIV
      infected women is unlikely to be due to a higher risk of direct obstetric
      complications, reducing this mortality will require non obstetric interventions
      involving access to ART in both pregnant and non-pregnant women.

PMID- 24124459
TI  - The systematic classification of gallbladder stones.
AB  - BACKGROUND: To develop a method for systematic classification of gallbladder
      stones, analyze the clinical characteristics of each type of stone and provide a
      theoretical basis for the study of the formation mechanism of different types of
      gallbladder stones. METHODOLOGY: A total of 807 consecutive patients with
      gallbladder stones were enrolled and their gallstones were studied. The material
      composition of gallbladder stones was analyzed using Fourier Transform Infrared
      spectroscopy and the distribution and microstructure of material components was
      observed with Scanning Electron Microscopy. The composition and distribution of
      elements were analyzed by an X-ray energy spectrometer. Gallbladder stones were
      classified accordingly, and then, gender, age, medical history and BMI of
      patients with each type of stone were analyzed. PRINCIPAL FINDINGS: Gallbladder
      stones were classified into 8 types and more than ten subtypes, including
      cholesterol stones (297), pigment stones (217), calcium carbonate stones (139),
      phosphate stones (12), calcium stearate stones (9), protein stones (3), cystine
      stones (1) and mixed stones (129). Mixed stones were those stones with two or
      more than two kinds of material components and the content of each component was
      similar. A total of 11 subtypes of mixed stones were found in this study.
      Patients with cholesterol stones were mainly female between the ages of 30 and
      50, with higher BMI and shorter medical history than patients with pigment stones
      (P<0.05), however, patients with pigment, calcium carbonate, phosphate stones
      were mainly male between the ages of 40 and 60. CONCLUSION: The systematic
      classification of gallbladder stones indicates that different types of stones
      have different characteristics in terms of the microstructure, elemental
      composition and distribution, providing an important basis for the mechanistic
      study of gallbladder stones.

PMID- 24124460
TI  - Inhibition of mTOR reduces anal carcinogenesis in transgenic mouse model.
AB  - The molecular mechanism of human anal squamous cell carcinoma (ASCC) is unclear,
      and the accumulating evidence indicate association of ASCC with the activation of
      the Akt/mTOR pathway. Here we describe a mouse model with spontaneous anal
      squamous cell cancer, wherein a combined deletion of Tgfbr1 and Pten in
      stratified squamous epithelia was induced using inducible K14-Cre.
      Histopathologic analyses confirmed that 33.3% of the mice showed increased
      susceptibility to ASCC and precancerous lesions. Biomarker analyses demonstrated
      that the activation of the Akt pathway in ASCC of the Tgfbr1 and Pten double
      knockout (2cKO) mouse was similar to that observed in human anal cancer.
      Chemopreventive experiments using mTOR inhibitor-rapamycin treatment
      significantly delayed the onset of the ASCC tumors and reduced the tumor burden
      in 2cKO mice by decreasing the phosphorylation of Akt and S6. This is the first
      conditional knockout mouse model used for investigating the contributions of
      viral and cellular factors in anal carcinogenesis without carcinogen-mediated
      induction, and it would provide a platform for assessing new therapeutic
      modalities for treating and/or preventing this type of cancer. 

PMID- 24124462
TI  - Characterization of transcription factor phenotypes within antigen-specific CD4+
      T cells using qualitative multiplex single-cell RT-PCR.
AB  - Current research on antigen specific CD4+ T cells indicates that there is
      functional and phenotypic heterogeneity within these populations, but the extent
      of this heterogeneity is poorly described. The CD134/CD25 assay allows live
      isolation of antigen specific cells in vitro for down-stream molecular analysis.
      Antigen specific CD4+ T cells were examined at the molecular level by lineage
      specific transcription factor profiling using qualitative multiplex single cell
      RT-PCR and Lock Nucleic Acid (LNA) probes allowed unbiased amplification and
      delineation of expression of Tbx21, Gata3, Rorc, Foxp3 and Bcl-6. It overcomes
      the limitations of previous assays by allowing identification of transcription
      factor mRNA in single antigen specific cells with high sensitivity (down to 10
      femtograms) and specificity. Patterns of responses can be robustly characterized
      using <200 cells based on exact binomial calculations. These results are
      reproducible with a CV of ~6%. The patterns of heterogeneity are stable within an
      individual antigen specific response but vary between responses to different
      antigens. Responses to CMV have a Th1 predominant profile (35.6% of responding
      cells expressing tbx21) whereas responses to Tetanus Toxoid have a Th2 biased
      profile (22% of responding cells expressing gata3), with unexpectedly high levels
      of Treg cells found in both populations. Here we describe a methodology that
      allows live isolation of Ag specific cells and transcription factor profiling at
      a single cell level to robustly delineate the different CD4+ T cell subsets
      within this population. This novel method is a powerful tool that can be used to
      study CD4+ T cell heterogeneity within extremely small populations of cells and
      where cell numbers are limited. 

PMID- 24124461
TI  - Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a
      Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
AB  - Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by
      mutations in GBA1 leading to defective glucocerebrosidase (GCase) function and
      consequent excess accumulation of glucosylceramide/glucosylsphingosine in
      visceral organs. Enzyme replacement therapy (ERT) with the biosimilars,
      imiglucerase (imig) or velaglucerase alfa (vela) improves/reverses the visceral
      disease. Comparative transcriptomic effects (microarray and mRNA-Seq) of no ERT
      and ERT (imig or vela) were done with liver, lung, and spleen from mice having
      Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects,
      dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays
      and their respective analytic tools, i.e. Mixed Model ANOVA (microarray), and
      DESeq and edgeR (mRNA-Seq). While similar gene expression patterns were observed
      with both platforms, mRNA-Seq identified more differentially expressed genes
      (DEGs) (~3-fold) than the microarrays. Among the three analytic tools, DESeq
      identified the maximum number of DEGs for all tissues and treatments. DESeq and
      edgeR comparisons revealed differences in DEGs identified. In 9V/null liver,
      spleen and lung, post-therapy transcriptomes approximated WT, were partially
      reverted, and had little change, respectively, and were concordant with the
      corresponding histological and biochemical findings. DEG overlaps were only 8-20%
      between mRNA-Seq and microarray, but the biological pathways were similar. Cell
      growth and proliferation, cell cycle, heme metabolism, and mitochondrial
      dysfunction were most altered with the Gaucher disease process. Imig and vela
      differentially affected specific disease pathways. Differential molecular
      responses were observed in direct transcriptome comparisons from imig- and vela
      treated tissues. These results provide cross-validation for the mRNA-Seq and
      microarray platforms, and show differences between the molecular effects of two
      highly structurally similar ERT biopharmaceuticals. 

PMID- 24124463
TI  - Competitive interactions of ligands and macromolecular crowders with maltose
      binding protein.
AB  - Cellular signaling involves a cascade of recognition events occurring in a
      complex environment with high concentrations of proteins, polysaccharides, and
      other macromolecules. The influence of macromolecular crowders on protein binding
      affinity through hard-core repulsion is well studied, and possible contributions
      of protein-crowder soft attraction have been implicated recently. Here we present
      direct evidence for weak association of maltose binding protein (MBP) with a
      polysaccharide crowder Ficoll, and that this association effectively competes
      with the binding of the natural ligand, maltose. Titration data over wide ranges
      of maltose and Ficoll concentrations fit well with a three-state competitive
      binding model. Broadening of MBP (1)H-(15)N TROSY spectra by the addition of
      Ficoll indicates weak protein-crowder association, and subsequent recovery of
      sharp NMR peaks upon addition of maltose indicates that the interactions of the
      crowder and the ligand with MBP are competitive. We hypothesize that, in the
      Escherichia coli periplasm, the competitive interactions of polysaccharides and
      maltose with MBP could allow MBP to shuttle between the peptidoglycan attached to
      the outer membrane and the ATP-binding cassette transporter in the inner
      membrane. 

PMID- 24124464
TI  - Identification and molecular characterization of YsaL (Ye3555): a novel negative
      regulator of YsaN ATPase in type three secretion system of enteropathogenic
      bacteria Yersinia enterocolitica.
AB  - Type Three Secretion (T3S) ATPases are involved in delivery of virulent factors
      from bacteria to their hosts (through injectisome) in an energy (ATP) dependent
      manner during pathogenesis. The activities of these ATPases are tightly
      controlled by their specific regulators. In Yersinia enterocolitica, YsaN was
      predicted as a putative ATPase of the Ysa-Ysp Type Three Secretion System (T3SS)
      based on sequence similarity with other T3S ATPases. However detailed study and
      characterization of YsaN and its regulation remains largely obscure. Here, in
      this study, we have successfully cloned, over-expressed, purified and
      characterized the molecular properties of YsaN from Yersinia enterocolitica. YsaN
      acts as a Mg(2+) dependent ATPase and exists in solution as higher order oligomer
      (dodecamer). The ATPase activity of oligomeric YsaN is several fold higher than
      the monomeric form. Furthermore, by employing in silico studies we have
      identified the existence of a negative regulator of YsaN--a hypothetical protein
      YE3555 (termed 'YsaL'). To verify the functionality of YsaL, we have evaluated
      the biochemical and biophysical properties of YsaL. Purified YsaL is dimeric in
      solution and strongly associates with YsaN to form a stable heterotrimeric YsaL
      YsaN complex (stoichiometry--2?1). The N terminal 6-20 residues of YsaN are
      invariably required for stable YsaL-YsaN complex formation. YsaL inhibited the
      ATPase activity of YsaN with a maximum inhibition at the molar ratio 2?1 (YsaL:
      YsaN). In short, our studies provide an insight into the presence of YsaN ATPase
      in Yersinia enterocolitica and its regulator YsaL. Our studies also correlate the
      functionality of one of the existing protein interaction networks that possibly
      is indispensable for the energy dependent process of Ysa-Ysp T3SS in pathogenic
      Yersinia enterocolitica.

PMID- 24124465
TI  - Signaling via class IA Phosphoinositide 3-kinases (PI3K) in human, breast-derived
      cell lines.
AB  - We have addressed the differential roles of class I Phosphoinositide 3-kinases
      (PI3K) in human breast-derived MCF10a (and iso-genetic derivatives) and MDA-MB
      231 and 468 cells. Class I PI3Ks are heterodimers of p110 catalytic (alpha, beta,
      delta and gamma) and p50-101 regulatory subunits and make the signaling lipid,
      phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) that can activate
      effectors, eg protein kinase B (PKB), and responses, eg migration. The
      PtdIns(3,4,5)P3-3-phosphatase and tumour-suppressor, PTEN inhibits this pathway.
      p110alpha, but not other p110s, has a number of onco-mutant variants that are
      commonly found in cancers. mRNA-seq data shows that MCF10a cells express
      p110beta>>alpha>delta with undetectable p110gamma. Despite this, EGF-stimulated
      phosphorylation of PKB depended upon p110alpha-, but not beta- or delta-
      activity. EGF-stimulated chemokinesis, but not chemotaxis, was also dependent
      upon p110alpha, but not beta- or delta- activity. In the presence of single,
      endogenous alleles of onco-mutant p110alpha (H1047R or E545K), basal, but not EGF
      stimulated, phosphorylation of PKB was increased and the effect of EGF was fully
      reversed by p110alpha inhibitors. Cells expressing either onco-mutant displayed
      higher basal motility and EGF-stimulated chemokinesis.This latter effect was,
      however, only partially-sensitive to PI3K inhibitors. In PTEN(-/-) cells, basal
      and EGF-stimulated phosphorylation of PKB was substantially increased, but the
      p110-dependency was variable between cell types. In MDA-MB 468s phosphorylation
      of PKB was significantly dependent on p110beta, but not alpha- or delta-
      activity; in PTEN(-/-) MCF10a it remained, like the parental cells, p110alpha
      dependent. Surprisingly, loss of PTEN suppressed basal motility and EGF
      stimulated chemokinesis. These results indicate that; p110alpha is required for
      EGF signaling to PKB and chemokinesis, but not chemotaxis; onco-mutant alleles of
      p110alpha augment signaling in the absence of EGF and may increase motility, in
      part, via acutely modulating PI3K-activity-independent mechanisms. Finally, we
      demonstrate that there is not a universal mechanism that up-regulates p110beta
      function in the absence of PTEN. 

PMID- 24124466
TI  - Comparative genomics reveals insight into virulence strategies of plant
      pathogenic oomycetes.
AB  - The kingdom Stramenopile includes diatoms, brown algae, and oomycetes. Plant
      pathogenic oomycetes, including Phytophthora, Pythium and downy mildew species,
      cause devastating diseases on a wide range of host species and have a significant
      impact on agriculture. Here, we report comparative analyses on the genomes of
      thirteen straminipilous species, including eleven plant pathogenic oomycetes, to
      explore common features linked to their pathogenic lifestyle. We report the
      sequencing, assembly, and annotation of six Pythium genomes and comparison with
      other stramenopiles including photosynthetic diatoms, and other plant pathogenic
      oomycetes such as Phytophthora species, Hyaloperonospora arabidopsidis, and
      Pythium ultimum var. ultimum. Novel features of the oomycete genomes include an
      expansion of genes encoding secreted effectors and plant cell wall degrading
      enzymes in Phytophthora species and an over-representation of genes involved in
      proteolytic degradation and signal transduction in Pythium species. A complete
      lack of classical RxLR effectors was observed in the seven surveyed Pythium
      genomes along with an overall reduction of pathogenesis-related gene families in
      H. arabidopsidis. Comparative analyses revealed fewer genes encoding enzymes
      involved in carbohydrate metabolism in Pythium species and H. arabidopsidis as
      compared to Phytophthora species, suggesting variation in virulence mechanisms
      within plant pathogenic oomycete species. Shared features between the oomycetes
      and diatoms revealed common mechanisms of intracellular signaling and
      transportation. Our analyses demonstrate the value of comparative genome analyses
      for exploring the evolution of pathogenesis and survival mechanisms in the
      oomycetes. The comparative analyses of seven Pythium species with the closely
      related oomycetes, Phytophthora species and H. arabidopsidis, and distantly
      related diatoms provide insight into genes that underlie virulence. 

PMID- 24124467
TI  - Meta-analysis on the associations of TLR2 gene polymorphisms with pulmonary
      tuberculosis susceptibility among Asian populations.
AB  - BACKGROUND: Publications regarding the associations of toll-like receptor 2
      (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB)
      susceptibility are inconsistent. A meta-analysis was conducted to investigate the
      relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.
      METHODS: A systematic search was performed for published studies on the
      relationship between TLR2 polymorphisms and PTB susceptibility. Information was
      gathered from each eligible study, and statistically analyzed. RESULTS: 6
      eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and
      8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were
      included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be
      associated with decreased PTB susceptibility (A vs. G: OR  = 3.02, 95% CI: 2.22
      4.12, P<0.001, GA+AA vs. GG: OR  = 2.69, 95% CI = 1.49-4.87, P = 0.001). In the
      subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a
      protective effect of PTB risk in Asians (A vs. G: OR  = 2.95, 95% CI: 1.91-4.55,
      P<0.001; GA+AA vs. GG: OR  = 3.59, 95% CI: 2.23-5.78, P<0.001), while no
      associations were observed in Caucasians. No significant associations between
      T597C polymorphism and PTB were found in the allele model (C vs. T: OR  = 0.95,
      95% CI: 0.86-1.04, P = 0.28), co-dominant model (CC vs. TT: OR  = 0.88, 95% CI =
      0.92-1.40, P = 0.25; CT vs. TT: OR  = 0.92, 95% CI = 0.80-1.06, P = 0.28),
      recessive model (CC vs. TT+TC: OR  = 0.96, 95% CI: 0.80-1.16, P = 0.69), or
      dominant model (TC+CC vs. TT: OR  = 0.93, 95% CI = 0.76-1.15, P = 0.51). The
      associations of T597C polymorphism with PTB susceptibility, in the ethnic
      specific analyses, were still not significant. CONCLUSION: TLR2 2258G allele may
      provide protective effects against PTB susceptibility, particularly among Asians,
      whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility.

PMID- 24124468
TI  - Gender differences in the association of smoking and drinking with the
      development of cognitive impairment.
AB  - Modifiable lifestyle-related factors such as smoking and alcohol drinking are
      associated with cognitive impairment in the elderly population but the
      relationships have shown various results. To evaluate the relationship of alcohol
      drinking and smoking in the early 60 s with the risk of developing incident
      cognitive impairment. In 1999, we evaluated cognitive function, smoking, and
      drinking status in 3,174 inhabitants aged 60-64 years in a rural area of Korea,
      with a follow-up assessment of cognitive function 7 years later. A total of 1,810
      individuals who did not show cognitive impairment at baseline were included. A
      stratified analysis was applied to evaluate how smoking and alcohol drinking
      affected the risk of developing cognitive impairment based on gender. Current
      smokers showed a higher risk for developing cognitive impairment than did never
      smokers (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.09-2.15). The OR
      for female current smokers compared with never smokers was 1.62 (95% CI, 1.05
      2.52), and smokers with higher pack-years were more likely to develop cognitive
      impairment than never smokers, showing a dose-response relationship (P for trend
      = 0.004). Frequent alcohol consumption increased the risk of developing cognitive
      impairment (OR, 1.68; 95% CI, 1.01-2.78), and a dose-response relationship was
      observed among male subjects (P for trend = 0.044). Infrequent drinking in
      females decreased the odds of developing cognitive impairment (OR, 0.67; 95% CI,
      0.42-1.00), whereas frequent drinking tended to increase the odds, although this
      trend was not significant, suggesting a U-shaped relationship. Although the
      sample was small for some analyses, especially in female, our data suggest that
      smoking and drinking in the early 60 s are associated with a risk of developing
      cognitive impairment, and this relationship is characterized by gender
      differences. 

PMID- 24124470
TI  - Substance use and access to health care and addiction treatment among homeless
      and vulnerably housed persons in three Canadian cities.
AB  - INTRODUCTION: We examined the prevalence of substance use disorders among
      homeless and vulnerably housed persons in three Canadian cities and its
      association with unmet health care needs and access to addiction treatment using
      baseline data from the Health and Housing in Transition Study. METHODS: In 2009,
      1191 homeless and vulnerably housed persons were recruited in Vancouver, Toronto,
      and Ottawa, Canada. Interviewer administered questionnaires collected data on
      socio-demographics, housing history, chronic health conditions, mental health
      diagnoses, problematic drug use (DAST-10>=6), problematic alcohol use
      (AUDIT>=20), unmet physical and mental health care needs, addiction treatment in
      the past 12 months. Three multiple logistic regression models were fit to examine
      the independent association of substance use with unmet physical health care
      need, unmet mental health care need, and addiction treatment. RESULTS: Substance
      use was highly prevalent, with over half (53%) screening positive for the DAST-10
      and 38% screening positive for the AUDIT. Problematic drug use was 29%,
      problematic alcohol use was lower at 16% and 7% had both problematic drug and
      alcohol use. In multiple regression models for unmet need, we found that
      problematic drug use was independently associated with unmet physical (adjusted
      odds ratio [AOR] 1.95; 95% confidence interval [CI] 1.43-2.64) and unmet mental
      (AOR 3.06; 95% CI 2.17-4.30) health care needs. Problematic alcohol use was not
      associated with unmet health care needs. Among those with problematic substance
      use, problematic drug use was associated with a greater likelihood of accessing
      addiction treatment compared to those with problematic alcohol use alone (AOR
      2.32; 95% CI 1.18-4.54). CONCLUSIONS: Problematic drug use among homeless and
      vulnerably housed individuals was associated with having unmet health care needs
      and accessing addiction treatment. Strategies to provide comprehensive health
      services including addiction treatment should be developed and integrated within
      community supported models of care.

PMID- 24124469
TI  - Cortical grey matter and subcortical white matter brain microstructural changes
      in schizophrenia are localised and age independent: a case-control diffusion
      tensor imaging study.
AB  - It is still unknown whether the structural brain impairments that characterize
      schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age
      related microstructural brain changes in cortical grey matter and subcortical
      white matter of patients affected by SZ. In this diffusion tensor imaging study,
      we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects,
      age and gender matched. We carried out analyses of covariance, with diagnosis as
      fixed factor and brain diffusion-related parameters as dependent variables, and
      controlled for the effect of education. White matter fractional anisotropy
      decreased in the entire age range spanned (18-65 years) in both SZ and HC and was
      significantly lower in younger patients with SZ, with no interaction (age by
      diagnosis) effect in fiber tracts including corpus callosum, corona radiata,
      thalamic radiations and external capsule. Also, grey matter mean diffusivity
      increased in the entire age range in both SZ and HC and was significantly higher
      in younger patients, with no age by diagnosis interaction in the left frontal
      operculum cortex, left insula and left planum polare and in the right temporal
      pole and right intracalcarine cortex. In individuals with SZ we found that
      localized brain cortical and white matter subcortical microstructural impairments
      appear early in life but do not worsen in the 18-65 year age range. 

PMID- 24124471
TI  - Combining genotype improvement and statistical media optimization for isoprenoid
      production in E. coli.
AB  - Isoprenoids are a large and diverse class of compounds that includes many high
      value natural products and are thus in great demand. To meet the increasing
      demand for isoprenoid compounds, metabolic engineering of microbes has been used
      to produce isoprenoids in an economical and sustainable manner. To achieve high
      isoprenoid yields using this technology, the availability of metabolic precursors
      feeding the deoxyxylulose phosphate (DXP) pathway, responsible for isoprenoid
      biosynthesis, has to be optimized. In this study, phosphoenolpyruvate, a vital
      DXP pathway precursor, was enriched by deleting the genes encoding the
      carbohydrate phosphotransferase system (PTS) in E. coli. Production of lycopene
      (a C40 isoprenoid) was maximized by optimizing growth medium and culture
      conditions. In optimized conditions, the lycopene yield from PTS mutant was seven
      fold higher than that obtained from the wild type strain. This resulted in the
      highest reported specific yield of lycopene produced from the DXP pathway in E.
      coli to date (20,000 ug/g dry cell weight). Both the copy number of the plasmid
      encoding the lycopene biosynthetic genes and the expression were found to be
      increased in the optimized media. Deletion of PTS together with a similar
      optimization strategy was also successful in enhancing the production of amorpha
      1,4-diene, a distinct C15 isoprenoid, suggesting that the approaches developed
      herein can be generally applied to optimize production of other isoprenoids. 

PMID- 24124472
TI  - The post-resuscitative urinalysis associate the survival of patients with non
      traumatic out-of-hospital cardiac arrest.
AB  - OBJECTIVE: To analyze whether urine output and urinalysis results are predictive
      of survival and neurologic outcomes in patients with non-traumatic out-of
      hospital cardiac arrest (OHCA). METHODS: Information was obtained from 1,340
      patients with non-traumatic OHCA who had achieved a sustained return of
      spontaneous circulation (ROSC). Factors that were associated with survival in the
      post-resuscitative period were evaluated. The association between urine output
      and fluid challenge in the early resuscitative period was analyzed and compared
      between the survivors and the non-survivors. The results of the initial
      urinalysis, including the presence of proteinuria and other findings, were used
      to evaluate the severity of vascular protein leakage and survival. The
      association between proteinuria and the neurologic outcomes of the survivors was
      also analyzed. The clinical features of capillary leakage were examined during
      the post-resuscitative period. RESULTS: Of the 1,340 patients, 312 survived. A
      greater urine output was associated with a higher chance of survival. The initial
      urine output increased in proportion to the amount of fluid that was administered
      during early resuscitation in the emergency department for the survivors but not
      for the non-survivors (p<0.05). In the initial urinalysis, proteinuria was
      strongly associated with survival, and severe proteinuria indicated significantly
      poorer neurologic outcomes (p<0.05 for both comparisons). Proteinuria was
      associated with a risk of developing signs of capillary leakage, including body
      mass index gain and pitting edema (both p<0.001). CONCLUSION: The severity of
      proteinuria during the early post-resuscitative period was predictive of
      survival.

PMID- 24124473
TI  - Ansamitocin P3 depolymerizes microtubules and induces apoptosis by binding to
      tubulin at the vinblastine site.
AB  - Maytansinoid conjugates are currently under different phases of clinical trials
      and have been showing promising activity for various types of cancers. In this
      study, we have elucidated the mechanism of action of ansamitocin P3, a structural
      analogue of maytansine for its anticancer activity. Ansamitocin P3 potently
      inhibited the proliferation of MCF-7, HeLa, EMT-6/AR1 and MDA-MB-231 cells in
      culture with a half-maximal inhibitory concentration of 20+/-3, 50+/-0.5, 140+/
      17, and 150+/-1.1 pM, respectively. Ansamitocin P3 strongly depolymerized both
      interphase and mitotic microtubules and perturbed chromosome segregation at its
      proliferation inhibitory concentration range. Treatment of ansamitocin P3
      activated spindle checkpoint surveillance proteins, Mad2 and BubR1 and blocked
      the cells in mitotic phase of the cell cycle. Subsequently, cells underwent
      apoptosis via p53 mediated apoptotic pathway. Further, ansamitocin P3 was found
      to bind to purified tubulin in vitro with a dissociation constant (Kd) of 1.3+/
      0.7 uM. The binding of ansamitocin P3 induced conformational changes in tubulin.
      A docking analysis suggested that ansamitocin P3 may bind partially to
      vinblastine binding site on tubulin in two different positions. The analysis
      indicated that the binding of ansamitocin P3 to tubulin is stabilized by hydrogen
      bonds. In addition, weak interactions such as halogen-oxygen interactions may
      also contribute to the binding of ansamitocin P3 to tubulin. The study provided a
      significant insight in understanding the antiproliferative mechanism of action of
      ansamitocin P3. 

PMID- 24124474
TI  - Evaluation and cross-comparison of lexical entities of biological interest
      (LexEBI).
AB  - MOTIVATION: Biomedical entities, their identifiers and names, are essential in
      the representation of biomedical facts and knowledge. In the same way, the
      complete set of biomedical and chemical terms, i.e. the biomedical "term space"
      (the "Lexeome"), forms a key resource to achieve the full integration of the
      scientific literature with biomedical data resources: any identified named entity
      can immediately be normalized to the correct database entry. This goal does not
      only require that we are aware of all existing terms, but would also profit from
      knowing all their senses and their semantic interpretation (ambiguities,
      nestedness). RESULT: This study compiles a resource for lexical terms of
      biomedical interest in a standard format (called "LexEBI"), determines the
      overall number of terms, their reuse in different resources and the nestedness of
      terms. LexEBI comprises references for protein and gene entries and their term
      variants and chemical entities amongst other terms. In addition, disease terms
      have been identified from Medline and PubmedCentral and added to LexEBI. Our
      analysis demonstrates that the baseforms of terms from the different semantic
      types show only little polysemous use. Nonetheless, the term variants of protein
      and gene names (PGNs) frequently contain species mentions, which should have been
      avoided according to protein annotation guidelines. Furthermore, the protein and
      gene entities as well as the chemical entities, both do comprise enzymes leading
      to hierarchical polysemy, and a large portion of PGNs make reference to a
      chemical entity. Altogether, according to our analysis based on the Medline
      distribution, 401,869 unique PGNs in the documents contain a reference to 25,022
      chemical entities, 3,125 disease terms or 1,576 species mentions. CONCLUSION:
      LexEBI delivers the complete biomedical and chemical Lexeome in a standardized
      representation (http://www.ebi.ac.uk/Rebholz-srv/LexEBI/). The resource provides
      the disease terms as open source content, and fully interlinks terms across
      resources.

PMID- 24124475
TI  - Directed forgetting of negative self-referential information is difficult: an
      FMRI study.
AB  - A large body of evidence suggested that both emotion and self-referential
      processing can enhance memory. However, it remains unclear how these two factors
      influence directed forgetting. This study speculates that directed forgetting of
      negative self-referential memory is more difficult than forgetting of other
      referential memory. To verify this speculation, we combined the directed
      forgetting paradigm with the self-reference task. The behavioral result suggested
      that although both self-referential and other-referential information can be
      directly forgotten, less self-referential information can be forgotten than other
      referential information. At the neural level, the forget instruction strongly
      activated the frontal cortex, suggesting that directed forgetting is not memory
      decay but an active process. In addition, compared with the negative other
      referential information, forgetting of the negative self-referential information
      were associated with a more widespread activation, including the orbital frontal
      gyrus (BA47), the inferior frontal gyrus (BA45, BA44), and the middle frontal
      gyrus. Our results suggest that forgetting of the self-referential information
      seems to be a more demanding and difficult process. 

PMID- 24124476
TI  - The discovery of a reciprocal relationship between tyrosine-kinase signaling and
      cullin neddylation.
AB  - While neddylation is known to activate cullin (CUL)-RING ubiquitin ligases
      (CRLs), its role in regulating T cell signaling is poorly understood. Using the
      investigational NEDD8 activating enzyme (NAE) inhibitor, MLN4924, we found that
      neddylation negatively regulates T cell receptor (TCR) signaling, as its
      inhibition increases IL-2 production, T cell proliferation and Treg development
      in vitro. We also discovered that loss of CUL neddylation occurs upon TCR
      signaling, and CRLs negatively regulate IL-2 production. Additionally, we found
      that tyrosine kinase signaling leads to CUL deneddylation in multiple cell types.
      These studies indicate that CUL neddylation is a global regulatory mechanism for
      tyrosine kinase signaling. 

PMID- 24124477
TI  - Discovery of a new genetic variant of methionine aminopeptidase from Streptococci
      with possible post-translational modifications: biochemical and structural
      characterization.
AB  - Protein N-terminal methionine excision is an essential co-translational process
      that occurs in the cytoplasm of all organisms. About 60-70% of the newly
      synthesized proteins undergo this modification. Enzyme responsible for the
      removal of initiator methionine is methionine aminopeptidase (MetAP), which is a
      dinuclear metalloprotease. This protein is conserved through all forms of life
      from bacteria to human except viruses. MetAP is classified into two isoforms,
      Type I and II. Removal of the map gene or chemical inhibition is lethal to
      bacteria and to human cell lines, suggesting that MetAP could be a good drug
      target. In the present study we describe the discovery of a new genetic variant
      of the Type I MetAP that is present predominantly in the streptococci bacteria.
      There are two inserts (insert one: 27 amino acids and insert two: four residues)
      within the catalytic domain. Possible glycosylation and phosphorylation
      posttranslational modification sites are identified in the 'insert one'.
      Biochemical characterization suggests that this enzyme behaves similar to other
      MetAPs in terms of substrate specificity. Crystal structure Type Ia MetAP from
      Streptococcus pneumoniae (SpMetAP1a) revealed that it contains two molecules in
      the asymmetric unit and well ordered inserts with structural features that
      corroborate the possible posttranslational modification. Both the new inserts
      found in the SpMetAP1a structurally align with the P-X-X-P motif found in the M.
      tuberculosis and human Type I MetAPs as well as the 60 amino acid insert in the
      human Type II enzyme suggesting possible common function. In addition, one of the
      beta-hairpins within in the catalytic domain undergoes a flip placing a residue
      which is essential for enzyme activity away from the active site and the beta
      hairpin loop of this secondary structure in the active site obstructing substrate
      binding. This is the first example of a MetAP crystallizing in the inactive form.

PMID- 24124478
TI  - Otitis media impacts hundreds of mouse middle and inner ear genes.
AB  - OBJECTIVE: Otitis media is known to alter expression of cytokine and other genes
      in the mouse middle ear and inner ear. However, whole mouse genome studies of
      gene expression in otitis media have not previously been undertaken. Ninety-nine
      percent of mouse genes are shared in the human, so these studies are relevant to
      the human condition. METHODS: To assess inflammation-driven processes in the
      mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic
      heat-killed Hemophilus influenza using untreated mice as controls. Middle and
      inner ear tissues were separately harvested at 6 hours, RNA extracted, and
      samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for
      expression of its 34,000 genes. RESULTS: Statistical analysis of gene expression
      compared to control mice showed significant alteration of gene expression in
      2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant
      middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081
      and 599 genes respectively. Significant middle and inner ear downregulation (fold
      change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis
      media is widely believed to be an exclusively middle ear process with little
      impact on the inner ear, the inner ear changes noted in this study were numerous
      and discrete from the middle ear responses. This suggests that the inner ear does
      indeed respond to otitis media and that its response is a distinctive process.
      Numerous new genes, previously not studied, are found to be affected by
      inflammation in the ear. CONCLUSION: Whole genome analysis via gene chip allows
      simultaneous examination of expression of hundreds of gene families influenced by
      inflammation in the middle ear. Discovery of new gene families affected by
      inflammation may lead to new approaches to the study and treatment of otitis
      media.

PMID- 24124479
TI  - Potential impact of influenza A/H1N1 pandemic and hand-gels on acute diarrhea
      epidemic in France.
AB  - BACKGROUND: The 2009 A/H1N1 influenza pandemic has received a great deal of
      attention from public health authorities. Our study examines whether this
      pandemic and the resulting public health measures could have impacted acute
      diarrhea, a prevalent, highly transmissible and historically monitored disease.
      METHODS: Using augmentation procedures of national data for the previous five
      years (2004-2009), we estimated the expected timing and incidence of acute
      diarrhea in France in 2009-2010 and evaluated differences with the observed. We
      also reviewed national hand gels for the same period. FINDINGS: Number of
      episodes of acute diarrhea in France in 2009-2010 was significantly lower than
      expected until the third week of December (-24%, 95% CI [-36%; -9%]), then
      significantly higher (+40%, 95% CI [22%; 62%]), leading to a surplus of 574,440
      episodes. The epidemic was delayed by 5 weeks with a peak 1.3 times higher than
      expected. Hand-gels sales inversely correlated with incidence of both influenza
      like illness and acute diarrheal disease. Among individuals >65 yo, no excess
      cases of influenza and no excess rebound in acute diarrhea were observed, despite
      similar delay in the onset of the seasonal diarrheal epidemic. INTERPRETATION:
      Our results suggest that at least one endemic disease had an unexpected behavior
      in 2009-2010. Acute diarrhea seems to have been controlled during the beginning
      of the pandemic in all age groups, but later peaked higher than expected in the
      younger population. The all-age delay in seasonal onset seems partly attributable
      to hand-gels use, while the differential magnitude of the seasonal epidemic
      between young and old, concurrent for both influenza and acute diarrhea, is
      compatible with disease interaction.

PMID- 24124480
TI  - Spatial analysis of slowly oscillating electric activity in the gut of mice using
      low impedance arrayed microelectrodes.
AB  - Smooth and elaborate gut motility is based on cellular cooperation, including
      smooth muscle, enteric neurons and special interstitial cells acting as pacemaker
      cells. Therefore, spatial characterization of electric activity in tissues
      containing these electric excitable cells is required for a precise understanding
      of gut motility. Furthermore, tools to evaluate spatial electric activity in a
      small area would be useful for the investigation of model animals. We thus
      employed a microelectrode array (MEA) system to simultaneously measure a set of
      8*8 field potentials in a square area of ~1 mm(2). The size of each recording
      electrode was 50*50 um(2), however the surface area was increased by fixing
      platinum black particles. The impedance of microelectrode was sufficiently low to
      apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto
      correlation and cross-correlation parameters characterized the spatial properties
      of spontaneous electric activity in the ileum of wild-type (WT) and W/W(v) mice,
      the latter serving as a model of impaired network of pacemaking interstitial
      cells. Namely, electric activities measured varied in both size and cooperativity
      in W/W(v) mice, despite the small area. In the ileum of WT mice, procedures
      suppressing the excitability of smooth muscle and neurons altered the propagation
      of spontaneous electric activity, but had little change in the period of
      oscillations. In conclusion, MEA with low impedance electrodes enables to measure
      slowly oscillating electric activity, and is useful to evaluate both histological
      and functional changes in the spatio-temporal property of gut electric activity. 

PMID- 24124481
TI  - Expression stabilities of candidate reference genes for RT-qPCR under different
      stress conditions in soybean.
AB  - Due to its accuracy, sensitivity and high throughput, real time quantitative PCR
      (RT-qPCR) has been widely used in analysing gene expression. The quality of data
      from such analyses is affected by the quality of reference genes used. Expression
      stabilities for nine candidate reference genes widely used in soybean were
      evaluated under different stresses in this study. Our results showed that EF1A
      and ACT11 were the best under salinity stress, TUB4, TUA5 and EF1A were the best
      under drought stress, ACT11 and UKN2 were the best under dark treatment, and EF1B
      and UKN2 were the best under virus infection. EF1B and UKN2 were the top two
      genes which can be reliably used in all of the stress conditions assessed. 

PMID- 24124482
TI  - The effect of four anaesthetic protocols for maintenance of anaesthesia on trans
      diaphragmatic pressure in dogs.
AB  - The diaphragm is the main inspiratory muscle and the main indicator of
      diaphragmatic contractility is the trans-diaphragmatic pressure (Pdi). The aim of
      this clinical study was to determine the effect of four different anaesthetic
      protocols on Pdi in anaesthetized healthy dogs. Eighty client-owned dogs were
      recruited in this clinical study. All the animals received dexmedetomidine and
      morphine as premedication and propofol for induction. Anaesthesia was maintained
      with one of four protocols: isoflurane (I), isoflurane with CRI of propofol (IP),
      isoflurane with CRI of fentanyl (IF), and isoflurane with CRI of ketamine (IK).
      When the surgical plane of anaesthesia was achieved, two balloon catheters were
      inserted, one into the stomach and one into the mid-third of the oesophagus for
      Pdi measurement. Pdi value was the highest in groups I (14.9+/-4.7 mmHg) and IK
      (15.2+/-3.5 mmHg) and the lowest in groups IP (12.2+/-3.2 mmHg) and IF (12.0+/
      5.9 mmHg). There was a statistically significant difference (p = 0.029) between
      groups IK and IF. PE'CO2 was statistically significantly higher (p<0.0005) in
      group IF (7.7+/-0.8 kPa) than in group IK (6.5+/-0.7 kPa). Isoflurane alone or
      isoflurane with ketamine for the maintenance of anaesthesia seem to better
      preserve the respiratory function and the diaphragmatic contractility than
      isoflurane with either propofol or fentanyl in dogs. Therefore, the use of
      isoflurane or isoflurane with ketamine may be of benefit when animals with
      respiratory problems have to be anaesthetized. 

PMID- 24124483
TI  - Integration profile and safety of an adenovirus hybrid-vector utilizing
      hyperactive sleeping beauty transposase for somatic integration.
AB  - We recently developed adenovirus/transposase hybrid-vectors utilizing the
      previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for
      somatic integration and we could show stabilized transgene expression in mice and
      a canine model for hemophilia B. However, the safety profile of these hybrid
      vectors with respect to vector dose and genotoxicity remains to be investigated.
      Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating
      vector dose settings. We found that in all mice which received the hyperactive SB
      transposase, transgene expression levels were stabilized in a dose-dependent
      manner and that the highest vector dose was accompanied by fatalities in mice. To
      analyze potential genotoxic side-effects due to somatic integration into host
      chromosomes, we performed a genome-wide integration site analysis using linker
      mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis
      of genomic DNA samples obtained from HSB5 treated female and male mice revealed a
      total of 1327 unique transposition events. Overall the chromosomal distribution
      pattern was close-to-random and we observed a random integration profile with
      respect to integration into gene and non-gene areas. Notably, when using the LM
      PCR protocol, 27 extra-chromosomal integration events were identified, most
      likely caused by transposon excision and subsequent transposition into the
      delivered adenoviral vector genome. In total, this study provides a careful
      evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid
      vectors. The obtained information will be useful when designing future
      preclinical studies utilizing hybrid-vectors in small and large animal models. 

PMID- 24124484
TI  - Both enhanced biocompatibility and antibacterial activity in Ag-decorated TiO2
      nanotubes.
AB  - In this study, Ag is electron-beam evaporated to modify the topography of anodic
      TiO2 nanotubes of different diameters to obtain an implant with enhanced
      antibacterial activity and biocompatibility. We found that highly hydrophilic as
      grown TiO2 nanotubes became poorly hydrophilic with Ag incorporation; however
      they could effectively recover their wettability to some extent under ultraviolet
      light irradiation. The results obtained from antibacterial tests suggested that
      the Ag-decorated TiO2 nanotubes could greatly inhibit the growth of
      Staphylococcus aureus. In vitro biocompatibility evaluation indicated that
      fibroblast cells exhibited an obvious diameter-dependent behavior on both as
      grown and Ag-decorated TiO2 nanotubes. Most importantly, of all samples, the
      smallest diameter (25-nm-diameter) Ag-decorated nanotubes exhibited the most
      obvious biological activity in promoting adhesion and proliferation of human
      fibroblasts, and this activity could be attributed to the highly irregular
      topography on a nanometric scale of the Ag-decorated nanotube surface. These
      experimental results demonstrate that by properly controlling the structural
      parameters of Ag-decorated TiO2 nanotubes, an implant surface can be produced
      that enhances biocompatibility and simultaneously boosts antibacterial activity. 

PMID- 24124485
TI  - Lactobacillus plantarum DK119 as a probiotic confers protection against influenza
      virus by modulating innate immunity.
AB  - Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage
      food was used as a probiotic to determine its antiviral effects on influenza
      virus. DK119 intranasal or oral administration conferred 100% protection against
      subsequent lethal infection with influenza A viruses, prevented significant
      weight loss, and lowered lung viral loads in a mouse model. The antiviral
      protective efficacy was observed in a dose and route dependent manner of DK119
      administration. Mice that were treated with DK119 showed high levels of cytokines
      IL-12 and IFN-gamma in bronchoalveolar lavage fluids, and a low degree of
      inflammation upon infection with influenza virus. Depletion of alveolar
      macrophage cells in lungs and bronchoalveolar lavages completely abrogated the
      DK119-mediated protection. Modulating host innate immunity of dendritic and
      macrophage cells, and cytokine production pattern appeared to be possible
      mechanisms by which DK119 exhibited antiviral effects on influenza virus
      infection. These results indicate that DK119 can be developed as a beneficial
      antiviral probiotic microorganism. 

PMID- 24124486
TI  - Effects on automatic attention due to exposure to pictures of emotional faces
      while performing Chinese word judgment tasks.
AB  - Two experiments were conducted to investigate the automatic processing of
      emotional facial expressions while performing low or high demand cognitive tasks
      under unattended conditions. In Experiment 1, 35 subjects performed low (judging
      the structure of Chinese words) and high (judging the tone of Chinese words)
      cognitive load tasks while exposed to unattended pictures of fearful, neutral, or
      happy faces. The results revealed that the reaction time was slower and the
      performance accuracy was higher while performing the low cognitive load task than
      while performing the high cognitive load task. Exposure to fearful faces resulted
      in significantly longer reaction times and lower accuracy than exposure to
      neutral faces on the low cognitive load task. In Experiment 2, 26 subjects
      performed the same word judgment tasks and their brain event-related potentials
      (ERPs) were measured for a period of 800 ms after the onset of the task stimulus.
      The amplitudes of the early component of ERP around 176 ms (P2) elicited by
      unattended fearful faces over frontal-central-parietal recording sites was
      significantly larger than those elicited by unattended neutral faces while
      performing the word structure judgment task. Together, the findings of the two
      experiments indicated that unattended fearful faces captured significantly more
      attention resources than unattended neutral faces on a low cognitive load task,
      but not on a high cognitive load task. It was concluded that fearful faces could
      automatically capture attention if residues of attention resources were available
      under the unattended condition. 

PMID- 24124487
TI  - Optimization and pharmacological validation of a leukocyte migration assay in
      zebrafish larvae for the rapid in vivo bioactivity analysis of anti-inflammatory
      secondary metabolites.
AB  - Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model
      for in vivo drug discovery. In this study, we explore the suitability of
      zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural
      products (NPs) and medicinal plants used in traditional medicine for the
      treatment of inflammatory disorders. First, we optimized a zebrafish assay for
      leukocyte migration. Inflammation was induced in four days post-fertilization
      (dpf) zebrafish larvae by tail transection and co-incubation with bacterial
      lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the
      zone of injury. Migrating zebrafish leukocytes were detected in situ by
      myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi
      quantitatively scored using a standardized scale of relative leukocyte migration
      (RLM). Pharmacological validation of this optimized assay was performed with a
      panel of anti-inflammatory drugs, demonstrating a concentration-responsive
      inhibition of leukocyte migration for both steroidal and non-steroidal anti
      inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity
      of structurally diverse NPs with well-documented anti-inflammatory properties.
      Finally, we further used this zebrafish-based assay to quantify the anti
      inflammatory activity in the aqueous and methanolic extracts of several medicinal
      plants. Our results indicate the suitability of this LPS-enhanced leukocyte
      migration assay in zebrafish larvae as a front-line screening platform in NP
      discovery, including for the bioassay-guided isolation of anti-inflammatory
      secondary metabolites from complex NP extracts. 

PMID- 24124489
TI  - Climate change may boost the invasion of the Asian needle ant.
AB  - Following its introduction from Asia to the USA, the Asian needle ant
      (Pachycondyla chinensis) is rapidly spreading into a wide range of habitats with
      great negative ecological affects. In addition, the species is a concern for
      human health because of its powerful, sometimes deadly, sting. Here, we assessed
      the potential of P. chinensis to spread further and to invade entirely new
      regions. We used species distribution models to assess suitable areas under
      current climatic conditions and in 2020, 2050 and 2080. With a consensus model,
      combining five different modelling techniques, three Global Circulation
      (climatic) Models and two CO2 emission scenarios, we generated world maps with
      suitable climatic conditions. Our models suggest that the species currently has a
      far greater potential distribution than its current exotic range, including large
      parts of the world landmass, including Northeast America, Southeast Asia and
      Southeast America. Climate change is predicted to greatly exacerbate the risk of
      P. chinensis invasion by increasing the suitable landmass by 64.9% worldwide,
      with large increases in Europe (+210.1%), Oceania (+75.1%), North America
      (+74.9%) and Asia (+62.7%). The results of our study suggest P. chinensis
      deserves increased attention, especially in the light of on-going climate change.

PMID- 24124488
TI  - Nuclear factor kappa-B is activated in the pulmonary vessels of patients with end
      stage idiopathic pulmonary arterial hypertension.
AB  - OBJECTIVES: To assess activation of the inflammatory transcription factor NF
      kappa B (NF-kappaB) in human idiopathic pulmonary arterial hypertension (PAH).
      BACKGROUND: Idiopathic PAH is a severe progressive disease characterized by
      pulmonary vascular remodeling and excessive proliferation of vascular cells.
      Increasing evidence indicates that inflammation is important in disease
      pathophysiology. METHODS: NF-kappaB-p65 and CD68, CD20 and CD45 were measured by
      immunohistochemistry and confocal microscopy on lung specimens from patients with
      idiopathic PAH (n = 12) and controls undergoing lung surgery (n = 14). Clinical
      data were recorded for all patients including invasive pulmonary hemodynamics for
      the PAH patients. Immunohistochemical images were analyzed by blinded observers
      to include standard pulmonary vascular morphometry; absolute macrophage
      counts/mm(2) and p65-positivity (p65+) using composite images and image-analysis
      software; and cytoplasmic:nuclear p65+ of individual pulmonary arterial
      endothelial and smooth muscle cells (PASMC) in 10-20 pulmonary arteries or
      arterioles per subject. The expression of ET-1 and CCL5 (RANTES) in whole lung
      was determined by RT-qPCR. RESULTS: Macrophage numbers were increased in
      idiopathic PAH versus controls (49.0+/-4.5 vs. 7.95+/-1.9 macrophages/100 mm(2),
      p<0.0001): these macrophages demonstrated more nuclear p65+ than in macrophages
      from controls (16.9+/-2.49 vs. 3.5+/-1.25%, p<0.001). An increase in p65+ was
      also seen in perivascular lymphocytes in patients with PAH. Furthermore, NF
      kappaB activation was increased in pulmonary arterial endothelial cells (62.3+/
      2.9 vs. 14.4+/-3.8, p<0.0001) and PASMC (22.6+/-2.3 vs. 11.2+/-2.0, p<0.001) in
      patients with PAH versus controls, with similar findings in arterioles. Gene
      expression of both ET-1 mRNA ((0.213+/-0.069 vs. 1.06+/-0.23, p<0.01) and CCL5
      (RANTES) (0.16+/-0.045 vs. 0.26+/-0.039, p<0.05) was increased in whole lung
      homogenates from patients with PAH. CONCLUSIONS: NF-kappaB is activated in
      pulmonary macrophages, lymphocytes, endothelial and PASMC in patients with end
      stage idiopathic PAH. Future research should determine whether NF-kappaB
      activation is a driver or bystander of pulmonary vascular inflammation and if the
      former, its potential role as a therapeutic target.

PMID- 24124490
TI  - NeSSM: a Next-generation Sequencing Simulator for Metagenomics.
AB  - BACKGROUND: Metagenomics can reveal the vast majority of microbes that have been
      missed by traditional cultivation-based methods. Due to its extremely wide range
      of application areas, fast metagenome sequencing simulation systems with high
      fidelity are in great demand to facilitate the development and comparison of
      metagenomics analysis tools. RESULTS: We present here a customizable metagenome
      simulation system: NeSSM (Next-generation Sequencing Simulator for Metagenomics).
      Combining complete genomes currently available, a community composition table,
      and sequencing parameters, it can simulate metagenome sequencing better than
      existing systems. Sequencing error models based on the explicit distribution of
      errors at each base and sequencing coverage bias are incorporated in the
      simulation. In order to improve the fidelity of simulation, tools are provided by
      NeSSM to estimate the sequencing error models, sequencing coverage bias and the
      community composition directly from existing metagenome sequencing data.
      Currently, NeSSM supports single-end and pair-end sequencing for both 454 and
      Illumina platforms. In addition, a GPU (graphics processing units) version of
      NeSSM is also developed to accelerate the simulation. By comparing the simulated
      sequencing data from NeSSM with experimental metagenome sequencing data, we have
      demonstrated that NeSSM performs better in many aspects than existing popular
      metagenome simulators, such as MetaSim, GemSIM and Grinder. The GPU version of
      NeSSM is more than one-order of magnitude faster than MetaSim. CONCLUSIONS: NeSSM
      is a fast simulation system for high-throughput metagenome sequencing. It can be
      helpful to develop tools and evaluate strategies for metagenomics analysis and
      it's freely available for academic users at
      http://cbb.sjtu.edu.cn/~ccwei/pub/software/NeSSM.php.

PMID- 24124491
TI  - Homologous pairing activities of two rice RAD51 proteins, RAD51A1 and RAD51A2.
AB  - In higher eukaryotes, RAD51 functions as an essential protein in homologous
      recombination and recombinational repair of DNA double strand breaks. During
      these processes, RAD51 catalyzes homologous pairing between single-stranded DNA
      and double-stranded DNA. Japonica cultivars of rice (Oryza sativa) encode two
      RAD51 proteins, RAD51A1 and RAD51A2, whereas only one RAD51 exists in yeast and
      mammals. However, the functional differences between RAD51A1 and RAD51A2 have not
      been elucidated, because their biochemical properties have not been
      characterized. In the present study, we purified RAD51A1 and RAD51A2, and found
      that RAD51A2 robustly promotes homologous pairing in vitro. RAD51A1 also
      possesses homologous-pairing activity, but it is only about 10% of the RAD51A2
      activity. Both RAD51A1 and RAD51A2 bind to ssDNA and dsDNA, and their DNA binding
      strictly requires ATP, which modulates the polymer formation activities of
      RAD51A1 and RAD51A2. These findings suggest that although both RAD51A1 and
      RAD51A2 have the potential to catalyze homologous pairing, RAD51A2 may be the
      major recombinase in rice. 

PMID- 24124492
TI  - Engineering salidroside biosynthetic pathway in hairy root cultures of Rhodiola
      crenulata based on metabolic characterization of tyrosine decarboxylase.
AB  - Tyrosine decarboxylase initializes salidroside biosynthesis. Metabolic
      characterization of tyrosine decarboxylase gene from Rhodiola crenulata (RcTYDC)
      revealed that it played an important role in salidroside biosynthesis.
      Recombinant 53 kDa RcTYDC converted tyrosine into tyramine. RcTYDC gene
      expression was induced coordinately with the expression of RcUDPGT (the last gene
      involved in salidroside biosynthesis) in SA/MeJA treatment; the expression of
      RcTYDC and RcUDPGT was dramatically upregulated by SA, respectively 49 folds and
      36 folds compared with control. MeJA also significantly increased the expression
      of RcTYDC and RcUDPGT in hairy root cultures. The tissue profile of RcTYDC and
      RcUDPGT was highly similar: highest expression levels found in stems, higher
      expression levels in leaves than in flowers and roots. The gene expressing levels
      were consistent with the salidroside accumulation levels. This strongly suggested
      that RcTYDC played an important role in salidroside biosynthesis in R. crenulata.
      Finally, RcTYDC was used to engineering salidroside biosynthetic pathway in R.
      crenulata hairy roots via metabolic engineering strategy of overexpression. All
      the transgenic lines showed much higher expression levels of RcTYDC than non
      transgenic one. The transgenic lines produced tyramine, tyrosol and salidroside
      at higher levels, which were respectively 3.21-6.84, 1.50-2.19 and 1.27-3.47
      folds compared with the corresponding compound in non-transgenic lines. In
      conclusion, RcTYDC overexpression promoted tyramine biosynthesis that facilitated
      more metabolic flux flowing toward the downstream pathway and as a result, the
      intermediate tyrosol was accumulated more that led to the increased production of
      the end-product salidroside. 

PMID- 24124493
TI  - Stable isotope labeled n-alkanes to assess digesta passage kinetics through the
      digestive tract of ruminants.
AB  - We describe the use of carbon stable isotope ((13)C) labeled n-alkanes as a
      potential internal tracer to assess passage kinetics of ingested nutrients in
      ruminants. Plant cuticular n-alkanes originating from intrinsically (13)C labeled
      ryegrass plants were pulse dosed intraruminally in four rumen-cannulated
      lactating dairy cows receiving four contrasting ryegrass silage treatments that
      differed in nitrogen fertilization level (45 or 90 kg nitrogen ha(-1)) and
      maturity (early or late). Passage kinetics through the gastrointestinal tract
      were derived from the delta(13)C (i.e. the ratio (13)C:(12)C) in apparently
      undigested fecal material. Isotopic enrichment was observed in a wide range of
      long-chain n-alkanes (C27-C36) and passage kinetics were determined for the most
      abundant C29, C31 and C33 n-alkanes, for which a sufficiently high response
      signal was detected by combustion isotope ratio mass spectrometry. Basal diet
      treatment and carbon chain length of n-alkanes did not affect fractional passage
      rates from the rumen (K 1) among individual n-alkanes (3.71-3.95%/h). Peak
      concentration time and transit time showed a quantitatively small, significant
      (p<=0.002) increase with carbon chain length. K 1 estimates were comparable to
      those of the (13)C labeled digestible dry matter fraction (3.38%/h; r = 0.61 to
      0.71; p<=0.012). A literature review has shown that n-alkanes are not fermented
      by microorganisms in the rumen and affirms no preferential depletion of (13)C
      versus (12)C. Our results suggest that (13)C labeled n-alkanes can be used as
      nutrient passage tracers and support the reliability of the delta(13)C signature
      of digestible feed nutrients as a tool to measure nutrient-specific passage
      kinetics. 

PMID- 24124494
TI  - Targeting and cytotoxicity of SapC-DOPS nanovesicles in pancreatic cancer.
AB  - Only a small number of promising drugs target pancreatic cancer, which is the
      fourth leading cause of cancer deaths with a 5-year survival of less than 5%. Our
      goal is to develop a new biotherapeutic agent in which a lysosomal protein
      (saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS) are
      assembled into nanovesicles (SapC-DOPS) for treating pancreatic cancer. A
      distinguishing feature of SapC-DOPS nanovesicles is their high affinity for
      phosphatidylserine (PS) rich microdomains, which are abnormally exposed on the
      membrane surface of human pancreatic tumor cells. To evaluate the role of
      external cell PS, in vitro assays were used to correlate PS exposure and the
      cytotoxic effect of SapC-DOPS in human tumor and nontumorigenic pancreatic cells.
      Next, pancreatic tumor xenografts (orthotopic and subcutaneous models) were used
      for tumor targeting and therapeutic efficacy studies with systemic SapC-DOPS
      treatment. We observed that the nanovesicles selectively killed human pancreatic
      cancer cells in vitro by inducing apoptotic death, whereas untransformed cells
      remained unaffected. This in vitro cytotoxic effect correlated to the surface
      exposure level of PS on the tumor cells. Using xenografts, animals treated with
      SapC-DOPS showed clear survival benefits and their tumors shrank or disappeared.
      Furthermore, using a double-tracking method in live mice, we showed that the
      nanovesicles were specifically targeted to orthotopically-implanted,
      bioluminescent pancreatic tumors. These data suggest that the acidic phospholipid
      PS is a biomarker for pancreatic cancer that can be effectively targeted for
      therapy utilizing cancer-selective SapC-DOPS nanovesicles. This study provides
      convincing evidence in support of developing a new therapeutic approach to
      pancreatic cancer. 

PMID- 24124495
TI  - Improved mass spectrometry assay for plasma hepcidin: detection and
      characterization of a novel hepcidin isoform.
AB  - Mass spectrometry (MS)-based assays for the quantification of the iron regulatory
      hormone hepcidin are pivotal to discriminate between the bioactive 25-amino acid
      form that can effectively block the sole iron transporter ferroportin and other
      naturally occurring smaller isoforms without a known role in iron metabolism.
      Here we describe the design, validation and use of a novel stable hepcidin
      25(+40) isotope as internal standard for quantification. Importantly, the
      relative large mass shift of 40 Da makes this isotope also suitable for easy-to
      use medium resolution linear time-of-flight (TOF) platforms. As expected,
      implementation of hepcidin-25(+40) as internal standard in our weak cation
      exchange (WCX) TOF MS method yielded very low inter/intra run coefficients of
      variation. Surprisingly, however, in samples from kidney disease patients, we
      detected a novel peak (m/z 2673.9) with low intensity that could be identified as
      hepcidin-24 and had previously remained unnoticed due to peak interference with
      the formerly used internal standard. Using a cell-based bioassay it was shown
      that synthetic hepcidin-24 was, like the -22 and -20 isoforms, a significantly
      less potent inducer of ferroportin degradation than hepcidin-25. During prolonged
      storage of plasma at room temperature, we observed that a decrease in plasma
      hepcidin-25 was paralleled by an increase in the levels of the hepcidin-24, -22
      and -20 isoforms. This provides first evidence that all determinants for the
      conversion of hepcidin-25 to smaller inactive isoforms are present in the
      circulation, which may contribute to the functional suppression of hepcidin-25,
      that is significantly elevated in patients with renal impairment. The present
      update of our hepcidin TOF MS assay together with improved insights in the source
      and preparation of the internal standard, and sample stability will further
      improve our understanding of circulating hepcidin and pave the way towards
      further optimization and standardization of plasma hepcidin assays. 

PMID- 24124496
TI  - SULF2 methylation is associated with in vitro cisplatin sensitivity and clinical
      efficacy for gastric cancer patients treated with a modified FOLFOX regimen.
AB  - OBJECTIVE: Biomarkers capable of discriminating the patients who are likely to
      respond to certain chemotherapeutic agents could improve the clinical efficiency.
      The sulfatases(SULFs) play a critical role in the pathogenesis of a variety of
      human cancers. Here, we focused our investigation on the prognostic and
      predictive impact of SULF2 methylation in gastric cancer. METHODS: Promoter CpG
      island methylation of SULF2 was analyzed in 100 gastric cancer samples. The in
      vitro sensitivity to cisplatin, docetaxel, gemcitabine, irinotecan and pemetrexed
      were determined by histoculture drug response assay(HDRA). Additionally, 56
      gastric cancer patients treated with a modified FOLFOX regimen(biweekly
      oxaliplatin plus 5-FU and folinic acid) were retrospectively analyzed to further
      evaluate the prognostic and predictive impact of SULF2 methylation in gastric
      cancer. RESULTS: Methylated SULF2(SULF2M) was detected in 28 patients, while the
      remaining 72 patients showed unmethylated SULF2(SULF2U, methylation rate: 28%).
      Samples with SULF2U were more sensitive to cisplatin than those with
      SULF2M(inhibition rate: 48.80% vs. 38.15%, P = 0.02), while samples with SULF2M
      were more sensitive to irinotecan than SULF2U(inhibition rate: 53.61% vs. 40.92%,
      P = 0.01). There were no association between SULF2 methylation and in vitro
      sensitivity to docetaxel, gemcitabine and pemetrexed. SULF2 methylation was found
      to have a significant association with cisplatin efficacy(SULF2M: 57.14%, SULF2U:
      80.56%, P = 0.02) and irinotecan efficacy(SULF2M: 89.29%, SULF2U: 62.50%, P =
      0.01). Among the 56 patients receiving the modified FOLFOX regimen, a significant
      association was observed between survival and SULF2 methylation status(SULF2M:
      309 days, 95% CI = 236 to 382 days; SULF2U: 481 days, 95% CI = 418 to 490 days; P
      = 0.02). Multivariate analysis revealed that SULF2 methylation was an independent
      prognostic factor of overall survival in gastric cancer patients treated with
      platinum-based chemotherapy. CONCLUSION: SULF2 methylation is negatively
      associated with cisplatin sensitivity in vitro. SULF2 methylation may be a novel
      prognostic biomarker for gastric cancer patients treated with platinum-based
      chemotherapy.

PMID- 24124497
TI  - A rapid and high-throughput quantitation assay of the nuclear factor kappaB
      activity using fluorescence correlation spectroscopy in the setting of clinical
      laboratories.
AB  - BACKGROUND: Transcription factor nuclear factor-kappaB (NF-kappaB) plays a key
      role in the regulation of immune responses to inflammation. However, convenient
      assay systems to quantitate the NF-kappaB activity level in a timely manner are
      not available in the setting of clinical laboratories. Therefore, we developed a
      novel and high-throughput quantitative assay based on fluorescence correlation
      spectroscopy (FCS) to detect the NF-kappaB activity level in cellular nuclear
      extracts and evaluated the performance of this method. The basic principle of
      this assay is to calculate the binding fraction of NF-kappaB to fluorescent
      labeled DNA probes, which contain NF-kappaB binding sites. METHODS: Non
      fluorescent competitive probes are employed to normalize the influence of the
      viscosity of the nuclear extracts between samples and to eliminate the influence
      of nonspecific binding of the fluorescent probes. To confirm accurate
      quantitation, human recombinant NF-kappaB p50 was mixed into U937 cell nuclear
      extracts, and the binding fraction of the fluorescent probes to NF-kappaB in the
      mixture was calculated for quantitation. To evaluate whether this method can be
      applied to measure the NF-kappaB activity in human lymphocytes, the NF-kappaB
      activity levels of systemic inflammatory response syndrome patients during
      perioperative periods were measured. RESULTS: The percentage recovery was 88.9%.
      The coefficients of variation of the intra-assay were approximately 10%. NF
      kappaB activity levels during the perioperative period can were successfully
      measured. The assay time for the FCS measurement was within 20 minutes.
      CONCLUSIONS: This assay system can be used to quantitate NF-kappaB activity
      levels in a timely manner in the setting of hospital laboratories.

PMID- 24124498
TI  - Comparison of cryptococcal antigenemia between antiretroviral naive and
      antiretroviral experienced HIV positive patients at two hospitals in Ethiopia.
AB  - BACKGROUND: Cryptococcal meningitis is a major cause of HIV/AIDS-related deaths
      in Africa. Cryptococcosis is a neglected killer. However, meningitis can be
      prevented by early cryptococcal antigen (CrAg) screening and preemptive
      antifungal treatment during a prolonged period of detectable, subclinical
      infection. We determined the prevalence of cryptococcal antigenemia in comparison
      to CD4 count and clinical symptoms. METHODS: We surveyed 254 consenting HIV
      infected participants to obtain demographic information and clinical history.
      Serum CrAg was measured by latex agglutination at two sites in the Oromia region
      of Ethiopia among all persons receiving a CD4 count. RESULTS: Of the 254
      participants, 127(50.0%) were ART-naive, 121(47.6%) were ART-experienced, and
      6(2.4%) were ART-defaulters. The prevalence of cryptococcal antigenemia was 10.2%
      overall being 14.2% among ART-naive, 4.1% among ART-experienced, and 50% (3/6)
      among ART-defaulters, irrespective of CD4 count. Cryptococcal antigenemia was
      more frequently detected from ART-naive patients (p = 0.012) and ART-defaulters
      (p = 0.001) compared with ART-experienced. Serum CrAg positivity was 20.9% in
      persons with CD4<=150 cells/uL, 12.2% in 151-200 cells/uL, 5.8% among 201-350
      CD4/uL, and none above 350 cells/uL. Potential meningitis symptoms were common in
      the outpatient cohort irrespective of CrAg-status, with only fever and altered
      mental status statistically more common in CrAg-positive compared to CrAg
      negative persons (P<0.05), yet no symptom had a positive predictive value >33%.
      CONCLUSION: We report a 20.9% cryptococcal antigenemia prevalence among those
      with CD4+ T cells count <=150 cells/uL, irrespective of ART status, with even
      higher CrAg prevalence in ART-naives and ART-defaulters. These groups are target
      populations for CrAg screening at entry into HIV care.

PMID- 24124499
TI  - The regulatory role of ferric uptake regulator (Fur) during anaerobic respiration
      of Shewanella piezotolerans WP3.
AB  - Ferric uptake regulator (Fur) is a global regulator that controls bacterial iron
      homeostasis. In this study, a fur deletion mutant of the deep-sea bacterium
      Shewanella piezotolerans WP3 was constructed. Physiological studies revealed that
      the growth rate of this mutant under aerobic conditions was only slightly lower
      than that of wild type (WT), but severe growth defects were observed under
      anaerobic conditions when different electron acceptors (EAs) were provided.
      Comparative transcriptomic analysis demonstrated that Fur is involved not only in
      classical iron homeostasis but also in anaerobic respiration. Fur exerted
      pleiotropic effects on the regulation of anaerobic respiration by controlling
      anaerobic electron transport, the heme biosynthesis system, and the cytochrome c
      maturation system. Biochemical assays demonstrated that levels of c-type
      cytochromes were lower in the fur mutant, consistent with the transcriptional
      profiling. Transcriptomic analysis and electrophoretic mobility shift assays
      revealed a primary regulation network for Fur in WP3. These results suggest that
      Fur may act as a sensor for anoxic conditions to trigger and influence the
      anaerobic respiratory system. 

PMID- 24124500
TI  - Estimation of the long-term care needs of stroke patients by integrating
      functional disability and survival.
AB  - OBJECTIVES: This study aimed to estimate the dynamic changes of different
      physical functional disabilities and life-time care needs for patients with
      stroke. DATA SOURCES AND STUDY DESIGN: We examined a hospital-based cohort
      including 16,043 patients who had their first stroke during 1995-2010. The
      Barthel Index (BI) was used to measure disability levels in 1,162 consecutive
      patients, with a total of 1,294 measurements at the stroke clinics and the
      rehabilitation wards, and a cross-sectional design. EXTRACTION METHODS: The
      survival function was extrapolated to lifetime by a semi-parametric method and
      multiplied with proportions of different disabilities over time to obtain the
      long-term care needs for different stroke subtypes. PRINCIPAL FINDINGS: On
      average, stroke patients would suffer at least 0.86 years with mild disability,
      1.24 years with moderate disability and 1.39 years with severe disability, as
      measured by the BI. Among these, patients with a cardio-embolic infarct or
      intracerebral hemorrhage (ICH) suffered more than 2 years of severe disability.
      Assistance in bathing was the most common need for care in stroke patients.
      CONCLUSIONS: Among different subtypes of stroke, cardio-embolic infarct and ICH
      lead to the longest durations of severe physical functional disability. The
      method presented in this work may also be applied to other chronic diseases and
      different functional disabilities.

PMID- 24124501
TI  - Explaining bacterial dispersion on leaf surfaces with an individual-based model
      (PHYLLOSIM).
AB  - We developed the individual-based model PHYLLOSIM to explain observed variation
      in the size of bacterial clusters on plant leaf surfaces (the phyllosphere).
      Specifically, we tested how different 'waterscapes' impacted the diffusion of
      nutrients from the leaf interior to the surface and the growth of individual
      bacteria on these nutrients. In the 'null' model or more complex 'patchy' models,
      the surface was covered with a continuous water film or with water drops of equal
      or different volumes, respectively. While these models predicted the growth of
      individual bacterial immigrants into clusters of variable sizes, they were unable
      to reproduce experimentally derived, previously published patterns of dispersion
      which were characterized by a much larger variation in cluster sizes and a
      disproportionate occurrence of clusters consisting of only one or two bacteria.
      The fit of model predictions to experimental data was about equally poor (<5%)
      regardless of whether the water films were continuous or patchy. Only by allowing
      individual bacteria to detach from developing clusters and re-attach elsewhere to
      start a new cluster, did PHYLLOSIM come much closer to reproducing experimental
      observations. The goodness of fit including detachment increased to about 70-80%
      for all waterscapes. Predictions of this 'detachment' model were further
      supported by the visualization and quantification of bacterial detachment and
      attachment events at an agarose-water interface. Thus, both model and experiment
      suggest that detachment of bacterial cells from clusters is an important
      mechanism underlying bacterial exploration of the phyllosphere. 

PMID- 24124502
TI  - Identification of Leptospira interrogans phospholipase C as a novel virulence
      factor responsible for intracellular free calcium ion elevation during macrophage
      death.
AB  - BACKGROUND: Leptospira-induced macrophage death has been confirmed to play a
      crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious
      disease. Intracellular free Ca(2+) concentration ([Ca(2+)]i) elevation induced by
      infection can cause cell death, but [Ca(2+)]i changes and high [Ca(2+)]i-induced
      death of macrophages due to infection of Leptospira have not been previously
      reported. METHODOLOGY/PRINCIPAL FINDINGS: We first used a Ca(2+)-specific
      fluorescence probe to confirm that the infection of L. interrogans strain Lai
      triggered a significant increase of [Ca(2+)]i in mouse J774A.1 or human THP-1
      macrophages. Laser confocal microscopic examination showed that the [Ca(2+)]i
      elevation was caused by both extracellular Ca(2+) influx through the purinergic
      receptor, P2X7, and Ca(2+) release from the endoplasmic reticulum, as seen by
      suppression of [Ca(2+)]i elevation when receptor-gated calcium channels were
      blocked or P2X7 was depleted. The LB361 gene product of the spirochete exhibited
      phosphatidylinositol phospholipase C (L-PI-PLC) activity to hydrolyze
      phosphatidylinositol-4,5-bisphosphate (PIP2) into inositol-1,4,5-trisphosphate
      (IP3), which in turn induces intracellular Ca(2+) release from endoplasmic
      reticulum, with the Km of 199 uM and Kcat of 8.566E-5 S(-1). Secretion of L-PI
      PLC from the spirochete into supernatants of leptospire-macrophage co-cultures
      and cytosol of infected macrophages was also observed by Western Blot assay.
      Lower [Ca(2+)]i elevation was induced by infection with a LB361-deficient
      leptospiral mutant, whereas transfection of the LB361 gene caused a mild increase
      in [Ca(2+)]i. Moreover, PI-PLCs (PI-PLC-beta3 and PI-PLC-gamma1) of the two
      macrophages were activated by phosphorylation during infection. Flow cytometric
      detection demonstrated that high [Ca(2+)]i increases induced apoptosis and
      necrosis of macrophages, while mild [Ca(2+)]i elevation only caused apoptosis.
      CONCLUSIONS/SIGNIFICANCE: This study demonstrated that L. interrogans infection
      induced [Ca(2+)]i elevation through extracellular Ca(2+) influx and intracellular
      Ca(2+) release cause macrophage apoptosis and necrosis, and the LB361 gene
      product was shown to be a novel PI-PLC of L. interrogans responsible for the
      [Ca(2+)]i elevation.

PMID- 24124503
TI  - Few effects of far transfer of working memory training in ADHD: a randomized
      controlled trial.
AB  - OBJECTIVE: Studies have shown that children with ADHD profit from working memory
      training, although few studies have investigated transfer effects
      comprehensively. The current Randomized Controlled Trial analyzes transfer to
      other neuropsychological (NP) domains, academic performance and everyday
      functioning at home and school. METHOD: Sixty-seven children with ADHD were
      randomized into a control group or a training group. The training group underwent
      Cogmed's RoboMemo program. All participants were assessed pre-training,
      immediately after and eight months later with a battery of NP tests, measures of
      mathematical and reading skills, as well as rating scales filled out by parents
      and teachers. RESULTS: There was a significant training effect in psychomotor
      speed, but not to any other NP measures. Reading and mathematics were improved.
      There were no training induced changes in symptom rating scales either at home or
      at school. The increased reading scores remained significant eight months later.
      CONCLUSION: The study is the most comprehensive study of transfer effects to
      date, and with mixed results compared to previous research. More research is
      needed regarding how to improve the training program and the conditions and
      thresholds for successful training. TRIAL REGISTRATION: Controlled-Trials.com
      ISRCTN19133620.

PMID- 24124504
TI  - High-throughput pseudovirion-based neutralization assay for analysis of natural
      and vaccine-induced antibodies against human papillomaviruses.
AB  - A highly sensitive, automated, purely add-on, high-throughput pseudovirion-based
      neutralization assay (HT-PBNA) with excellent repeatability and run-to-run
      reproducibility was developed for human papillomavirus types (HPV) 16, 18, 31,
      45, 52, 58 and bovine papillomavirus type 1. Preparation of 384 well assay plates
      with serially diluted sera and the actual cell-based assay are separated in time,
      therefore batches of up to one hundred assay plates can be processed
      sequentially. A mean coefficient of variation (CV) of 13% was obtained for anti
      HPV 16 and HPV 18 titers for a standard serum tested in a total of 58 repeats on
      individual plates in seven independent runs. Natural antibody response was
      analyzed in 35 sera from patients with HPV 16 DNA positive cervical
      intraepithelial neoplasia grade 2+ lesions. The new HT-PBNA is based on Gaussia
      luciferase with increased sensitivity compared to the previously described manual
      PBNA (manPBNA) based on secreted alkaline phosphatase as reporter. Titers
      obtained with HT-PBNA were generally higher than titers obtained with the
      manPBNA. A good linear correlation (R(2) = 0.7) was found between HT-PBNA titers
      and anti-HPV 16 L1 antibody-levels determined by a Luminex bead-based GST-capture
      assay for these 35 sera and a Kappa-value of 0.72, with only 3 discordant sera in
      the low titer range. In addition to natural low titer antibody responses the high
      sensitivity of the HT-PBNA also allows detection of cross-neutralizing antibodies
      induced by commercial HPV L1-vaccines and experimental L2-vaccines. When
      analyzing the WHO international standards for HPV 16 and 18 we determined an
      analytical sensitivity of 0.864 and 1.105 mIU, respectively. 

PMID- 24124505
TI  - Comparison of two voltage-sensitive dyes and their suitability for long-term
      imaging of neuronal activity.
AB  - One of the key approaches for studying neural network function is the
      simultaneous measurement of the activity of many neurons. Voltage-sensitive dyes
      (VSDs) simultaneously report the membrane potential of multiple neurons, but
      often have pharmacological and phototoxic effects on neuronal cells. Yet, to
      study the homeostatic processes that regulate neural network function long-term
      recordings of neuronal activities are required. This study aims to test the
      suitability of the VSDs RH795 and Di-4-ANEPPS for optically recording pattern
      generating neurons in the stomatogastric nervous system of crustaceans with an
      emphasis on long-term recordings of the pyloric central pattern generator. We
      demonstrate that both dyes stain pyloric neurons and determined an optimal
      concentration and light intensity for optical imaging. Although both dyes
      provided sufficient signal-to-noise ratio for measuring membrane potentials, Di-4
      ANEPPS displayed a higher signal quality indicating an advantage of this dye over
      RH795 when small neuronal signals need to be recorded. For Di-4-ANEPPS, higher
      dye concentrations resulted in faster and brighter staining. Signal quality,
      however, only depended on excitation light strength, but not on dye
      concentration. RH795 showed weak and slowly developing phototoxic effects on the
      pyloric motor pattern as well as slow bleaching of the staining and is thus the
      better choice for long-term experiments. Low concentrations and low excitation
      intensities can be used as, in contrast to Di-4-ANEPPS, the signal-to-noise ratio
      was independent of excitation light strength. In summary, RH795 and Di-4-ANEPPS
      are suitable for optical imaging in the stomatogastric nervous system of
      crustaceans. They allow simultaneous recording of the membrane potential of
      multiple neurons with high signal quality. While Di-4-ANEPPS is better suited for
      short-term experiments that require high signal quality, RH795 is a better
      candidate for long-term experiments since it has only minor effects on the motor
      pattern. 

PMID- 24124506
TI  - Developmental stage of parasites influences the structure of fish-parasite
      networks.
AB  - Specialized interactions tend to be more common in systems that require strong
      reciprocal adaptation between species, such as those observed between parasites
      and hosts. Parasites exhibit a high diversity of species and life history
      strategies, presenting host specificity which increases the complexity of these
      antagonistic systems. However, most studies are limited to the description of
      interactions between a few parasite and host species, which restricts our
      understanding of these systems as a whole. We investigated the effect of the
      developmental stage of the parasite on the structure of 30 metazoan fish-parasite
      networks, with an emphasis on the specificity of the interactions, connectance
      and modularity. We assessed the functional role of each species in modular
      networks and its interactions within and among the modules according to the
      developmental stage (larval and adult) and taxonomic group of the parasites. We
      observed that most parasite and host species perform a few interactions but that
      parasites at the larval stage tended to be generalists, increasing the network
      connectivity within and among modules. The parasite groups did not differ among
      each other in the number of interactions within and among the modules when
      considering only species at the larval stage. However, the same groups of adult
      individuals differed from each other in their interaction patterns, which were
      related to variations in the degree of host specificity at this stage. Our
      results show that the interaction pattern of fishes with parasites, such as
      acanthocephalans, cestodes, digeneans and nematodes, is more closely associated
      with their developmental stage than their phylogenetic history. This finding
      corroborates the hypothesis that the life history of parasites results in
      adaptations that cross phylogenetic boundaries. 

PMID- 24124507
TI  - In vivo wall shear measurements within the developing zebrafish heart.
AB  - Physical forces can influence the embryonic development of many tissues. Within
      the cardiovascular system shear forces resulting from blood flow are known to be
      one of the regulatory signals that shape the developing heart. A key challenge in
      investigating the role of shear forces in cardiac development is the ability to
      obtain shear force measurements in vivo. Utilising the zebrafish model system we
      have developed a methodology that allows the shear force within the developing
      embryonic heart to be determined. Accurate wall shear measurement requires two
      essential pieces of information; high-resolution velocity measurements near the
      heart wall and the location and orientation of the heart wall itself. We have
      applied high-speed brightfield imaging to capture time-lapse series of blood flow
      within the beating heart between 3 and 6 days post-fertilization. Cardiac-phase
      filtering is applied to these time-lapse images to remove the heart wall and
      other slow moving structures leaving only the red blood cell movement. Using
      particle image velocimetry to calculate the velocity of red blood cells in
      different regions within the heart, and using the signal-to-noise ratio of the
      cardiac-phase filtered images to determine the boundary of blood flow, and
      therefore the position of the heart wall, we have been able to generate the
      necessary information to measure wall shear in vivo. We describe the methodology
      required to measure shear in vivo and the application of this technique to the
      developing zebrafish heart. We identify a reduction in shear at the ventricular
      bulbar valve between 3 and 6 days post-fertilization and demonstrate that the
      shear environment of the ventricle during systole is constantly developing
      towards a more uniform level. 

PMID- 24124508
TI  - Null mutants of individual RABA genes impact the proportion of different cell
      wall components in stem tissue of Arabidopsis thaliana.
AB  - In Arabidopsis, and other plants, the RABA GTPases (orthologous to the Rab11a of
      mammals) have expanded in number and diversity and have been shown to belong to
      eight sub clades, some of which have been implicated in controlling vesicles that
      traffic cell wall polymers and enzymes that synthesise or modify them to the cell
      wall. In order to investigate this, we have investigated whether T-DNA insertion
      knockouts of individual RABA genes belonging to different sub clades, impact on
      the composition of the plant cell wall. Single gene knockouts of the RABA1, RABA2
      and RABA4 sub clades primarily affected the percentage composition of pectin,
      cellulose and hemicellulose within the cell wall, respectively, despite having no
      obvious phenotype in the whole plant. We hypothesise that vesicles carrying
      specific types of cargoes from the Golgi to the cell surface may be regulated by
      particular sub types of RABA proteins, a finding that could have wider
      implications for how trafficking systems work and could be a useful tool in cell
      wall research and other fields of plant biology. 

PMID- 24124509
TI  - Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome
      activation by inhibiting reactive oxygen species generation and protein kinase C
      alpha/delta activation.
AB  - Bamboo vinegar (BV), a natural liquid derived from the condensation produced
      during bamboo charcoal production, has been used in agriculture and as a food
      additive, but its application to immune modulation has not been reported. Here,
      we demonstrated that BV has anti-inflammatory activities both in vitro and in
      vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide
      levels in, and interleukin-6 secretion by, lipopolysaccharide-activated
      macrophages without affecting tumor necrosis factor-alpha secretion and
      cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV
      involved decreased reactive oxygen species production and protein kinase C
      alpha/delta activation. Furthermore, creosol (2-methoxy-4-methylphenol) was
      indentified as the major anti-inflammatory compound in BV. Impaired cytokine
      expression and NLR family, pyrin domain-containing 3 (NLRP3) inflammasome
      activation was seen in mice treated with creosol. These findings provide insights
      into how BV regulates inflammation and suggest that it may be a new source for
      the development of anti-inflammatory agents or a healthy supplement for
      preventing and ameliorating inflammation- and NLRP3 inflammasome-related
      diseases, including metabolic syndrome. 

PMID- 24124510
TI  - Genomic and functional analyses of the 2-aminophenol catabolic pathway and
      partial conversion of its substrate into picolinic acid in Burkholderia
      xenovorans LB400.
AB  - 2-aminophenol (2-AP) is a toxic nitrogen-containing aromatic pollutant.
      Burkholderia xenovorans LB400 possess an amn gene cluster that encodes the 2-AP
      catabolic pathway. In this report, the functionality of the 2-aminophenol pathway
      of B. xenovorans strain LB400 was analyzed. The amnRJBACDFEHG cluster located at
      chromosome 1 encodes the enzymes for the degradation of 2-aminophenol. The
      absence of habA and habB genes in LB400 genome correlates with its no growth on
      nitrobenzene. RT-PCR analyses in strain LB400 showed the co-expression of amnJB,
      amnBAC, amnACD, amnDFE and amnEHG genes, suggesting that the amn cluster is an
      operon. RT-qPCR showed that the amnB gene expression was highly induced by 2-AP,
      whereas a basal constitutive expression was observed in glucose, indicating that
      these amn genes are regulated. We propose that the predicted MarR-type
      transcriptional regulator encoded by the amnR gene acts as repressor of the amn
      gene cluster using a MarR-type regulatory binding sequence. This report showed
      that LB400 resting cells degrade completely 2-AP. The amn gene cluster from
      strain LB400 is highly identical to the amn gene cluster from P. knackmussi
      strain B13, which could not grow on 2-AP. However, we demonstrate that B.
      xenovorans LB400 is able to grow using 2-AP as sole nitrogen source and glucose
      as sole carbon source. An amnBA (-) mutant of strain LB400 was unable to grow
      with 2-AP as nitrogen source and glucose as carbon source and to degrade 2-AP.
      This study showed that during LB400 growth on 2-AP this substrate was partially
      converted into picolinic acid (PA), a well-known antibiotic. The addition of PA
      at lag or mid-exponential phase inhibited LB400 growth. The MIC of PA for strain
      LB400 is 2 mM. Overall, these results demonstrate that B. xenovorans strain LB400
      posses a functional 2-AP catabolic central pathway, which could lead to the
      production of picolinic acid. 

PMID- 24124511
TI  - A source of terrestrial organic carbon to investigate the browning of aquatic
      ecosystems.
AB  - There is growing evidence that terrestrial ecosystems are exporting more
      dissolved organic carbon (DOC) to aquatic ecosystems than they did just a few
      decades ago. This "browning" phenomenon will alter the chemistry, physics, and
      biology of inland water bodies in complex and difficult-to-predict ways.
      Experiments provide an opportunity to elucidate how browning will affect the
      stability and functioning of aquatic ecosystems. However, it is challenging to
      obtain sources of DOC that can be used for manipulations at ecologically relevant
      scales. In this study, we evaluated a commercially available source of humic
      substances ("Super Hume") as an analog for natural sources of terrestrial DOC.
      Based on chemical characterizations, comparative surveys, and whole-ecosystem
      manipulations, we found that the physical and chemical properties of Super Hume
      are similar to those of natural DOC in aquatic and terrestrial ecosystems. For
      example, Super Hume attenuated solar radiation in ways that will not only
      influence the physiology of aquatic taxa but also the metabolism of entire
      ecosystems. Based on its chemical properties (high lignin content, high quinone
      content, and low C:N and C:P ratios), Super Hume is a fairly recalcitrant, low
      quality resource for aquatic consumers. Nevertheless, we demonstrate that Super
      Hume can subsidize aquatic food webs through 1) the uptake of dissolved organic
      constituents by microorganisms, and 2) the consumption of particulate fractions
      by larger organisms (i.e., Daphnia). After discussing some of the caveats of
      Super Hume, we conclude that commercial sources of humic substances can be used
      to help address pressing ecological questions concerning the increased export of
      terrestrial DOC to aquatic ecosystems. 

PMID- 24124512
TI  - Development of a conditional Mesd (mesoderm development) allele for functional
      analysis of the low-density lipoprotein receptor-related family in defined
      tissues.
AB  - The Low-density lipoprotein receptor-Related Protein (LRP) family members are
      essential for diverse processes ranging from the regulation of gastrulation to
      the modulation of lipid homeostasis. Receptors in this family bind and
      internalize a diverse array of ligands in the extracellular matrix (ECM). As a
      consequence, LRPs regulate a wide variety of cellular functions including, but
      not limited to lipid metabolism, membrane composition, cell motility, and cell
      signaling. Not surprisingly, mutations in single human LRPs are associated with
      defects in cholesterol metabolism and development of atherosclerosis,
      abnormalities in bone density, or aberrant eye vasculature, and may be a
      contributing factor in development of Alzheimer's disease. Often, members of this
      diverse family of receptors perform overlapping roles in the same tissues,
      complicating the analysis of their function through conventional targeted
      mutagenesis. Here, we describe development of a mouse Mesd (Mesoderm Development)
      conditional knockout allele, and demonstrate that ubiquitous deletion of Mesd
      using Cre-recombinase blocks gastrulation, as observed in the traditional
      knockout and albino-deletion phenotypes. This conditional allele will serve as an
      excellent tool for future characterization of the cumulative contribution of LRP
      members in defined tissues. 

PMID- 24124513
TI  - Porphyromonas gingivalis regulates TREM-1 in human polymorphonuclear neutrophils
      via its gingipains.
AB  - The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface
      receptor of the immunoglobulin superfamily, with the capacity to amplify pro
      inflammatory cytokine production and regulate apoptosis. Polymorphonuclear
      neutrophils (PMNs) are the first line of defence against infection, and a major
      source of TREM-1. Porphyromonas gingivalis is a Gram-negative anaerobe highly
      implicated in the inflammatory processes governing periodontal disease, which is
      characterized by the destruction of the tooth-supporting tissues. It expresses a
      number of virulence factors, including the cysteine proteinases (or gingipains).
      The aim of this in vitro study was to investigate the effect of P. gingivalis on
      TREM-1 expression and production by primary human PMNs, and to evaluate the role
      of its gingipains in this process. After 4 h of challenge, P. gingivalis enhanced
      TREM-1 expression as identified by quantitative real-time PCR. This was followed
      by an increase in soluble (s)TREM-1 secretion over a period of 18 h, as
      determined by ELISA. At this time-point, the P. gingivalis-challenged PMNs
      exhibited diminished TREM-1 cell-membrane staining, as identified by flow
      cytometry and confocal laser scanning microscopy. Furthermore engagement of TREM
      1, by means of anti-TREM-1 antibodies, enhanced the capacity of P. gingivalis to
      stimulate interleukin (IL)-8 production. Conversely, antagonism of TREM-1 using a
      synthetic peptide resulted in reduction of IL-8 secretion. Using isogenic P.
      gingivalis mutant strains, we identified the Arg-gingipain to be responsible for
      shedding of sTREM-1 from the PMN surface, whereas the Lys-gingipain had the
      capacity to degrade TREM-1. In conclusion, the differential regulation of TREM-1
      by the P. gingivalis gingipains may present a novel mechanism by which P.
      gingivalis manipulates the host innate immune response helping to establish
      chronic periodontal inflammation. 

PMID- 24124514
TI  - Th17 cell-mediated neuroinflammation is involved in neurodegeneration of abeta1
      42-induced Alzheimer's disease model rats.
AB  - Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has
      been reported to participate in pathogenesis of Alzheimer's disease (AD).
      However, the involvement of adaptive immune cells, such as CD4(+) T lymphocytes,
      in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17
      (Th17) cells, a subpopulation of CD4(+) T cells with high proinflammation, and
      show the implication of the cells in neurodegeneration of AD. Amyloid beta1-42
      (Abeta1-42) was bilaterally injected into hippocampus of rats to induce AD. On
      days 7 and 14 following the Abeta1-42 administration, escape latency of the rats
      in Morris water maze was increased, expression of amyloid precursor protein was
      upregulated, but expression of protein phosphatase 2A was downregulated in the
      hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region.
      Infusion of FITC-linked albumin in blood circulation and combination with
      immunostaining of hippocampal sections for RORgamma, a specific transcriptional
      factor of Th17 cells, demonstrated blood-brain barrier (BBB) disruption and Th17
      cells' infiltration into brain parenchyma of AD rats. Expression of Th17
      proinflammatory cytokines, interleukin (IL)-17 and IL-22, was increased in the
      hippocampus, and concentrations of the two cytokines were elevated in both the
      cerebrospinal fluid and the serum in AD occurrence and development. Compared with
      intact or saline-treated control rats, AD animals indicated an upregulated
      expression of Fas and FasL in the hippocampus. Further, the immunofluorescent
      histochemistry on AD hippocampal sections with NeuN, RORgamma, Fas and FasL
      displayed that Fas was principally expressed by neurons and FasL was
      predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL
      and NeuN double-labeled cells increased. These results suggest that Th17 cells,
      which were infiltrated into AD brain parenchyma, participate in neuroinflammation
      and neurodegeneration of AD by release of proinflammatory cytokines and by direct
      action on neurons via Fas/FasL apoptotic pathway. 

PMID- 24124515
TI  - The mechanisms and boundary conditions of the Einstellung effect in chess:
      evidence from eye movements.
AB  - In a wide range of problem-solving settings, the presence of a familiar solution
      can block the discovery of better solutions (i.e., the Einstellung effect). To
      investigate this effect, we monitored the eye movements of expert and novice
      chess players while they solved chess problems that contained a familiar move
      (i.e., the Einstellung move), as well as an optimal move that was located in a
      different region of the board. When the Einstellung move was an advantageous (but
      suboptimal) move, both the expert and novice chess players who chose the
      Einstellung move continued to look at this move throughout the trial, whereas the
      subset of expert players who chose the optimal move were able to gradually
      disengage their attention from the Einstellung move. However, when the
      Einstellung move was a blunder, all of the experts and the majority of the
      novices were able to avoid selecting the Einstellung move, and both the experts
      and novices gradually disengaged their attention from the Einstellung move. These
      findings shed light on the boundary conditions of the Einstellung effect, and
      provide convergent evidence for Bilalic, McLeod, & Gobet (2008)'s conclusion that
      the Einstellung effect operates by biasing attention towards problem features
      that are associated with the familiar solution rather than the optimal solution. 

PMID- 24124517
TI  - Density- and size-dependent winter mortality and growth of late Chaoborus
      flavicans larvae.
AB  - Winter processes such as overwinter survival and growth of individuals can have
      wide-ranging consequences for population dynamics and communities within and
      across seasons. In freshwater organisms winter processes have been mainly studied
      in fish despite that invertebrates also have substantial impacts on lake and pond
      food webs. One of the major invertebrate consumers in lake and ponds is the
      planktonic larvae of the dipteran insect Chaoborus spec. However, while much is
      known about Chaoborus feeding ecology, behaviour and structuring role in food
      webs, its winter ecology and how it affects its populations are poorly
      understood. Here size- and density-dependent winter mortality and body growth of
      late Chaoborus flavicans larvae were quantified over naturally occurring size and
      density ranges in autumn and under natural winter conditions using two field
      enclosure experiments. Winter mortality increased with autumn density but
      decreased with autumn body size while winter growth rates decreased with autumn
      density and body sizes. There was also a density- and size-independent background
      mortality component. The proportion of pupae found in spring decreased strongly
      and exponentially with autumn density. These results may explain the commonly
      observed univoltine life cycle and multi-annual density fluctuations in northern
      Chaoborus populations. They further demonstrate the relevance of winter processes
      and conditions for freshwater invertebrates and ecosystems. 

PMID- 24124516
TI  - Xanthine oxidase mediates hypoxia-inducible factor-2alpha degradation by
      intermittent hypoxia.
AB  - Sleep-disordered breathing with recurrent apnea produces chronic intermittent
      hypoxia (IH). We previously reported that IH leads to down-regulation of HIF
      2alpha protein via a calpain-dependent signaling pathway resulting in oxidative
      stress. In the present study, we delineated the signaling pathways associated
      with calpain-dependent HIF-2alpha degradation in cell cultures and rats subjected
      to chronic IH. Reactive oxygen species (ROS) scavengers prevented HIF-2alpha
      degradation by IH and ROS mimetic decreased HIF-2alpha protein levels in rat
      pheochromocytoma PC12 cell cultures, suggesting that ROS mediate IH-induced HIF
      2alpha degradation. IH activated xanthine oxidase (XO) by increased proteolytic
      conversion of xanthine dehydrogenase to XO. ROS generated by XO activated
      calpains, which contributed to HIF-2alpha degradation by IH. Calpain-induced HIF
      2alpha degradation involves C-terminus but not the N-terminus of the HIF-2alpha
      protein. Pharmacological blockade as well as genetic knock down of XO prevented
      IH induced calpain activation and HIF-2alpha degradation in PC12 cells. Systemic
      administration of allopurinol to rats prevented IH-induced hypertension,
      oxidative stress and XO activation in adrenal medulla. These results demonstrate
      that ROS generated by XO activation mediates IH-induced HIF-2alpha degradation
      via activation of calpains. 

PMID- 24124518
TI  - Oxidative stress enhances neurodegeneration markers induced by herpes simplex
      virus type 1 infection in human neuroblastoma cells.
AB  - Mounting evidence suggests that Herpes simplex virus type 1 (HSV-1) is involved
      in the pathogenesis of Alzheimer's disease (AD). Previous work from our
      laboratory has shown HSV-1 infection to induce the most important pathological
      hallmarks of AD brains. Oxidative damage is one of the earliest events of AD and
      is thought to play a crucial role in the onset and development of the disease.
      Indeed, many studies show the biomarkers of oxidative stress to be elevated in AD
      brains. In the present work the combined effects of HSV-1 infection and oxidative
      stress on Abeta levels and autophagy (neurodegeneration markers characteristic of
      AD) were investigated. Oxidative stress significantly potentiated the
      accumulation of intracellular Abeta mediated by HSV-1 infection, and further
      inhibited its secretion to the extracellular medium. It also triggered the
      accumulation of autophagic compartments without increasing the degradation of
      long-lived proteins, and enhanced the inhibition of the autophagic flux induced
      by HSV-1. These effects of oxidative stress were not due to enhanced virus
      replication. Together, these results suggest that HSV-1 infection and oxidative
      damage interact to promote the neurodegeneration events seen in AD. 

PMID- 24124519
TI  - Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila
      neuromuscular junction.
AB  - Retrograde growth factors regulating synaptic plasticity at the neuromuscular
      junction (NMJ) in Drosophila have long been predicted but their discovery has
      been scarce. In vertebrates, such retrograde factors produced by the muscle
      include GDNF and the neurotrophins (NT: NGF, BDNF, NT3 and NT4). NT superfamily
      members have been identified throughout the invertebrates, but so far no
      functional in vivo analysis has been carried out at the NMJ in invertebrates. The
      NT family of proteins in Drosophila is formed of DNT1, DNT2 and Spatzle (Spz),
      with sequence, structural and functional conservation relative to mammalian NTs.
      Here, we investigate the functions of Drosophila NTs (DNTs) at the larval NMJ.
      All three DNTs are expressed in larval body wall muscles, targets for motor
      neurons. Over-expression of DNTs in neurons, or the activated form of the Spz
      receptor, Toll(10b), in neurons only, rescued the semi-lethality of spz(2) and
      DNT1(41), DNT2(e03444) double mutants, indicating retrograde functions in
      neurons. In spz(2) mutants, DNT1(41), DNT2(e03444) double mutants, and upon over
      expression of the DNTs, NMJ size and bouton number increased. Boutons were
      morphologically abnormal. Mutations in spz and DNT1,DNT2 resulted in decreased
      number of active zones per bouton and decreased active zone density per terminal.
      Alterations in DNT function induced ghost boutons and synaptic debris. Evoked
      junction potentials were normal in spz(2) mutants and DNT1(41), DNT2(e03444)
      double mutants, but frequency and amplitude of spontaneous events were reduced in
      spz(2) mutants suggesting defective neurotransmission. Our data indicate that
      DNTs are produced in muscle and are required in neurons for synaptogenesis. Most
      likely alterations in DNT function and synapse formation induce NMJ plasticity
      leading to homeostatic adjustments that increase terminal size restoring overall
      synaptic transmission. Data suggest that Spz functions with neuron-type
      specificity at the muscle 4 NMJ, and DNT1 and DNT2 function together at the
      muscles 6,7 NMJ.

PMID- 24124520
TI  - Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated
      by DNA interstrand cross-linking agents.
AB  - Modulation of the DNA repair pathway is an emerging target for the development of
      anticancer drugs. DNA interstrand cross-links (ICLs), one of the most severe
      forms of DNA damage caused by anticancer drugs such as cisplatin and mitomycin C
      (MMC), activates the Fanconi anemia (FA)/BRCA DNA repair pathway. Inhibition of
      the FA/BRCA pathway can enhance the cytotoxic effects of ICL-inducing anticancer
      drugs and can reduce anticancer drug resistance. To find FA/BRCA pathway
      inhibitory small molecules, we established a cell-based high-content screening
      method for quantitating the activation of the FA/BRCA pathway by measuring FANCD2
      foci on DNA lesions and then applied our method to chemical screening. Using
      commercial LOPAC1280 chemical library screening, ouabain was identified as a
      competent FA/BRCA pathway inhibitory compound. Ouabain, a member of the cardiac
      glycoside family, binds to and inhibits Na(+)/K(+)-ATPase and has been used to
      treat heart disease for many years. We observed that ouabain, as well as other
      cardiac glycoside family members--digitoxin and digoxin--down-regulated FANCD2
      and FANCI mRNA levels, reduced monoubiquitination of FANCD2, inhibited FANCD2
      foci formation on DNA lesions, and abrogated cell cycle arrest induced by MMC
      treatment. These inhibitory activities of ouabain required p38 MAPK and were
      independent of cellular Ca(2+) ion increase or the drug uptake-inhibition effect
      of ouabain. Furthermore, we found that ouabain potentiated the cytotoxic effects
      of MMC in tumor cells. Taken together, we identified an additional effect of
      ouabain as a FA/BRCA pathway-inhibiting chemosensitization compound. The results
      of this study suggest that ouabain may serve as a chemosensitizer to ICL-inducing
      anticancer drugs.

PMID- 24124521
TI  - Distinct effects of EGFR ligands on human mammary epithelial cell
      differentiation.
AB  - Based on gene expression patterns, breast cancers can be divided into subtypes
      that closely resemble various developmental stages of normal mammary epithelial
      cells (MECs). Thus, understanding molecular mechanisms of MEC development is
      expected to provide critical insights into initiation and progression of breast
      cancer. Epidermal growth factor receptor (EGFR) and its ligands play essential
      roles in normal and pathological mammary gland. Signals through EGFR is required
      for normal mammary gland development. Ligands for EGFR are over-expressed in a
      significant proportion of breast cancers, and elevated expression of EGFR is
      associated with poorer clinical outcome. In the present study, we examined the
      effect of signals through EGFR on MEC differentiation using the human telomerase
      reverse transcriptase (hTERT)-immortalized human stem/progenitor MECs which
      express cytokeratin 5 but lack cytokeratin 19 (K5(+)K19(-) hMECs). As reported
      previously, these cells can be induced to differentiate into luminal and
      myoepithelial cells under appropriate culture conditions. K5(+)K19(-) hMECs
      acquired distinct cell fates in response to EGFR ligands epidermal growth factor
      (EGF), amphiregulin (AREG) and transforming growth factor alpha (TGFalpha) in
      differentiation-promoting MEGM medium. Specifically, presence of EGF during in
      vitro differentiation supported development into both luminal and myoepithelial
      lineages, whereas cells differentiated only towards luminal lineage when EGF was
      replaced with AREG. In contrast, substitution with TGFalpha led to
      differentiation only into myoepithelial lineage. Chemical inhibition of the MEK
      Erk pathway, but not the phosphatidylinositol 3-kinase (PI3K)-AKT pathway,
      interfered with K5(+)K19(-) hMEC differentiation. The present data validate the
      utility of the K5(+)K19(-) hMEC cells for modeling key features of human MEC
      differentiation. This system should be useful in studying molecular/biochemical
      mechanisms of human MEC differentiation. 

PMID- 24124522
TI  - How to use not-always-reliable binding site information in protein-protein
      docking prediction.
AB  - In many protein-protein docking algorithms, binding site information is used to
      help predicting the protein complex structures. Using correct and accurate
      binding site information can increase protein-protein docking success rate
      significantly. On the other hand, using wrong binding sites information should
      lead to a failed prediction, or, at least decrease the success rate. Recently,
      various successful theoretical methods have been proposed to predict the binding
      sites of proteins. However, the predicted binding site information is not always
      reliable, sometimes wrong binding site information could be given. Hence there is
      a high risk to use the predicted binding site information in current docking
      algorithms. In this paper, a softly restricting method (SRM) is developed to
      solve this problem. By utilizing predicted binding site information in a proper
      way, the SRM algorithm is sensitive to the correct binding site information but
      insensitive to wrong information, which decreases the risk of using predicted
      binding site information. This SRM is tested on benchmark 3.0 using purely
      predicted binding site information. The result shows that when the predicted
      information is correct, SRM increases the success rate significantly; however,
      even if the predicted information is completely wrong, SRM only decreases success
      rate slightly, which indicates that the SRM is suitable for utilizing predicted
      binding site information. 

PMID- 24124523
TI  - Motions add, orientations don't, in the human visual system.
AB  - Humans can distinguish between contours of similar orientation, and between
      directions of visual motion. There is consensus that both of these capabilities
      depend on selective activation of tuned neural channels. The bandwidths of these
      tuned channels are estimated here by modelling previously published empirical
      data. Human subjects were presented with a rapid stream of randomly oriented
      gratings, or randomly directed motions, and asked to respond when they saw a
      target stimulus. For the orientation task, subjects were less likely to respond
      when two preceding orientations were close to the target orientation but differed
      from each other, presumably due to a failure of summation. For the motion data,
      by contrast, subjects were more likely to respond when the vector sum of two
      previous directions was in the target direction. Fitting a cortical signal
      processing model to these data showed that the direction bandwidth of motion
      sensors is about three times the bandwidth of orientation sensors, and that it is
      the large bandwidth that allows the summation of motion stimuli. The differing
      bandwidths of orientation and motion sensors presumably equip them for differing
      tasks, such as orientation discrimination and estimation of heading,
      respectively. 

PMID- 24124524
TI  - Signals of historical interlocus gene conversion in human segmental duplications.
AB  - Standard methods of DNA sequence analysis assume that sequences evolve
      independently, yet this assumption may not be appropriate for segmental
      duplications that exchange variants via interlocus gene conversion (IGC). Here,
      we use high quality multiple sequence alignments from well-annotated segmental
      duplications to systematically identify IGC signals in the human reference
      genome. Our analysis combines two complementary methods: (i) a paralog quartet
      method that uses DNA sequence simulations to identify a statistical excess of
      sites consistent with inter-paralog exchange, and (ii) the alignment-based method
      implemented in the GENECONV program. One-quarter (25.4%) of the paralog families
      in our analysis harbor clear IGC signals by the quartet approach. Using GENECONV,
      we identify 1477 gene conversion tracks that cumulatively span 1.54 Mb of the
      genome. Our analyses confirm the previously reported high rates of IGC in
      subtelomeric regions and Y-chromosome palindromes, and identify multiple novel
      IGC hotspots, including the pregnancy specific glycoproteins and the
      neuroblastoma breakpoint gene families. Although the duplication history of a
      paralog family is described by a single tree, we show that IGC has introduced
      incredible site-to-site variation in the evolutionary relationships among
      paralogs in the human genome. Our findings indicate that IGC has left significant
      footprints in patterns of sequence diversity across segmental duplications in the
      human genome, out-pacing the contributions of single base mutation by orders of
      magnitude. Collectively, the IGC signals we report comprise a catalog that will
      provide a critical reference for interpreting observed patterns of DNA sequence
      variation across duplicated genomic regions, including targets of recent adaptive
      evolution in humans. 

PMID- 24124525
TI  - Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse
      model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin
      supplementation.
AB  - Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative lysosomal
      storage disorders characterized by vision loss, mental and motor deficits, and
      spontaneous seizures. Neuropathological analyses of autopsy material from NCL
      patients and animal models revealed brain atrophy closely associated with glial
      activity. Earlier reports also noticed loss of retinal cells and reactive gliosis
      in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular
      phenotype of CLN6 (nclf) mice, an established mouse model for variant-late
      infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking,
      electroretinography, and mRNA expression were used to characterize retinal
      morphology and function as well as the responses of Muller cells and microglia.
      Our histological data showed a severe and progressive degeneration in the CLN6
      (nclf) retina co-inciding with reactive Muller glia. Furthermore, a prominent
      phenotypic transformation of ramified microglia to phagocytic, bloated, and
      mislocalized microglial cells was identified in CLN6 (nclf) retinas. These events
      overlapped with a rapid loss of visual perception and retinal function. Based on
      the strong microglia reactivity we hypothesized that dietary supplementation with
      immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA), could
      ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that
      treatment of three-week-old CLN6 (nclf) mice with either 5% DHA or 0.6% curcumin
      for 30 weeks resulted in a reduced number of amoeboid reactive microglia and
      partially improved retinal function. DHA-treatment also improved the morphology
      of CLN6 (nclf) retinas with a preserved thickness of the photoreceptor layer in
      most regions of the retina. Our results suggest that microglial reactivity
      closely accompanies disease progression in the CLN6 (nclf) retina and both
      processes can be attenuated with dietary supplemented immuno-modulating
      compounds. 

PMID- 24124526
TI  - Identification and characterization of a novel monoterpene synthase from soybean
      restricted to neryl diphosphate precursor.
AB  - Terpenes are important defensive compounds against herbivores and pathogens.
      Here, we report the identification of a new monoterpene synthase gene, GmNES,
      from soybean. The transcription of GmNES was up-regulated in soybean plants that
      were infested with cotton leafworm (Prodenia litura), mechanically wounded or
      treated with salicylic acid (SA). Gas chromatography-mass spectrometry (GC-MS)
      analysis revealed that recombinant GmNES enzyme exclusively produced nerol,
      generated from a newly identified substrate for monoterpene synthase: neryl
      diphosphate (NPP). This finding indicates that GmNES is a nerol synthase gene in
      soybean. Subcellular localization using GFP fusions showed that GmNES localized
      to the chloroplasts. Transgenic tobacco overexpressing GmNES was generated. In
      dual-choice assays, the GmNES-expressing tobacco lines significantly repelled
      cotton leafworm. In feeding tests with transgenic plants, the growth and
      development of cotton leafworm were significantly retarded. This study confirms
      the ecological role of terpenoids and provides new insights into their metabolic
      engineering in transgenic plants. 

PMID- 24124527
TI  - Overexpression of OsEXPA8, a root-specific gene, improves rice growth and root
      system architecture by facilitating cell extension.
AB  - Expansins are unique plant cell wall proteins that are involved in cell wall
      modifications underlying many plant developmental processes. In this work, we
      investigated the possible biological role of the root-specific alpha-expansin
      gene OsEXPA8 in rice growth and development by generating transgenic plants.
      Overexpression of OsEXPA8 in rice plants yielded pleiotropic phenotypes of
      improved root system architecture (longer primary roots, more lateral roots and
      root hairs), increased plant height, enhanced leaf number and enlarged leaf size.
      Further study indicated that the average cell length in both leaf and root
      vascular bundles was enhanced, and the cell growth in suspension cultures was
      increased, which revealed the cellular basis for OsEXPA8-mediated rice plant
      growth acceleration. Expansins are thought to be a key factor required for cell
      enlargement and wall loosening. Atomic force microscopy (AFM) technology revealed
      that average wall stiffness values for 35S::OsEXPA8 transgenic suspension
      cultured cells decreased over six-fold compared to wild-type counterparts during
      different growth phases. Moreover, a prominent change in the wall polymer
      composition of suspension cells was observed, and Fourier-transform infrared
      (FTIR) spectra revealed a relative increase in the ratios of the
      polysaccharide/lignin content in cell wall compositions of OsEXPA8
      overexpressors. These results support a role for expansins in cell expansion and
      plant growth. 

PMID- 24124528
TI  - Persistent changes in circulating and intestinal gammadelta T cell subsets,
      invariant natural killer T cells and mucosal-associated invariant T cells in
      children and adults with coeliac disease.
AB  - Coeliac disease is a chronic small intestinal immune-mediated enteropathy
      precipitated by exposure to dietary gluten in genetically predisposed
      individuals. The only current therapy is a lifelong gluten free diet. While much
      work has focused on the gliadin-specific adaptive immune response in coeliac
      disease, little is understood about the involvement of the innate immune system.
      Here we used multi-colour flow cytometry to determine the number and frequency of
      gammadelta T cells (Vdelta1, Vdelta2 and Vdelta3 subsets), natural killer cells,
      CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells,
      in blood and duodenum from adults and children with coeliac disease and healthy
      matched controls. All circulating innate lymphocyte populations were
      significantly decreased in adult, but not paediatric coeliac donors, when
      compared with healthy controls. Within the normal small intestine, we noted that
      Vdelta3 cells were the most abundant gammadelta T cell type in the adult
      epithelium and lamina propria, and in the paediatric lamina propria. In contrast,
      patients with coeliac disease showed skewing toward a predominant Vdelta1
      profile, observed for both adult and paediatric coeliac disease cohorts,
      particularly within the gut epithelium. This was concurrent with decreases in all
      other gut lymphocyte subsets, suggesting a specific involvement of Vdelta1 cells
      in coeliac disease pathogenesis. Further analysis showed that gammadelta T cells
      isolated from the coeliac gut display an activated, effector memory phenotype,
      and retain the ability to rapidly respond to in vitro stimulation. A profound
      loss of CD56 expression in all lymphocyte populations was noted in the coeliac
      gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in
      coeliac disease patients of all ages, persisting even after elimination of gluten
      from the diet. This may lead to impaired immunity, and could potentially account
      for the increased incidence of autoimmune co-morbidity. 

PMID- 24124529
TI  - B7-H1 expression is associated with poor prognosis in colorectal carcinoma and
      regulates the proliferation and invasion of HCT116 colorectal cancer cells.
AB  - BACKGROUND AND OBJECTIVE: The investigation concerning the B7-H1 expression in
      colorectal cancer cells is at an early stage. It is unclear whether B7-H1
      expression may have diagnostic or prognostic value in colorectal carcinoma.
      Additionally, how B7-H1 is associated with the clinical features of colorectal
      carcinoma is not known. In order to investigate the relationship between B7-H1
      and colorectal cancer, we analyzed B7-H1 expression and its effect in clinical
      specimens and HCT116 cells. METHODS: Paraffin-embedded specimens from 143
      eligible patients were used to investigate the expression of CD274 by
      immunohistochemistry. We also examined whether B7-H1 itself may be related to
      cell proliferation, apoptosis, migration and invasion in colon cancer HCT116
      cells. RESULTS: Our results show that B7-H1 was highly expressed in colorectal
      carcinoma and was significantly associated with cell differentiation status and
      TNM (Tumor Node Metastasis) stage. Patients with positive B7-H1 expression showed
      a trend of shorter survival time. Using multivariate analysis, we demonstrate
      that positive B7-H1 expression is an independent predictor of colorectal
      carcinoma prognosis. Our results indicate that B7-H1 silencing with siRNA
      inhibits cell proliferation, migration and invasion. Furthermore, cell apoptosis
      was also increased by B7-H1 inhibition. CONCLUSIONS: Positive B7-H1 expression is
      an independent predictor for colorectal carcinoma prognosis. Moreover, knockdown
      of B7-H1 can inhibit cell proliferation, migration and invasion.

PMID- 24124530
TI  - Structure and stability insights into tumour suppressor p53 evolutionary related
      proteins.
AB  - The p53 family of genes and their protein products, namely, p53, p63 and p73,
      have over one billion years of evolutionary history. Advances in computational
      biology and genomics are enabling studies of the complexities of the molecular
      evolution of p53 protein family to decipher the underpinnings of key biological
      conditions spanning from cancer through to various metabolic and developmental
      disorders and facilitate the design of personalised medicines. However, a
      complete understanding of the inherent nature of the thermodynamic and structural
      stability of the p53 protein family is still lacking. This is due, to a degree,
      to the lack of comprehensive structural information for a large number of
      homologous proteins and to an incomplete knowledge of the intrinsic factors
      responsible for their stability and how these might influence function. Here we
      investigate the thermal stability, secondary structure and folding properties of
      the DNA-binding domains (DBDs) of a range of proteins from the p53 family using
      biophysical methods. While the N- and the C-terminal domains of the p53 family
      show sequence diversity and are normally targets for post-translational
      modifications and alternative splicing, the central DBD is highly conserved.
      Together with data obtained from Molecular Dynamics simulations in solution and
      with structure based homology modelling, our results provide further insights
      into the molecular properties of evolutionary related p53 proteins. We identify
      some marked structural differences within the p53 family, which could account for
      the divergence in biological functions as well as the subtleties manifested in
      the oligomerization properties of this family. 

PMID- 24124531
TI  - Noise-aided logic in an electronic analog of synthetic genetic networks.
AB  - We report the experimental verification of noise-enhanced logic behaviour in an
      electronic analog of a synthetic genetic network, composed of two repressors and
      two constitutive promoters. We observe good agreement between circuit
      measurements and numerical prediction, with the circuit allowing for robust logic
      operations in an optimal window of noise. Namely, the input-output
      characteristics of a logic gate is reproduced faithfully under moderate noise,
      which is a manifestation of the phenomenon known as Logical Stochastic Resonance.
      The two dynamical variables in the system yield complementary logic behaviour
      simultaneously. The system is easily morphed from AND/NAND to OR/NOR logic. 

PMID- 24124532
TI  - Improved part-of-speech prediction in suffix analysis.
AB  - MOTIVATION: Predicting the part of speech (POS) tag of an unknown word in a
      sentence is a significant challenge. This is particularly difficult in
      biomedicine, where POS tags serve as an input to training sophisticated
      literature summarization techniques, such as those based on Hidden Markov Models
      (HMM). Different approaches have been taken to deal with the POS tagger
      challenge, but with one exception--the TnT POS tagger--previous publications on
      POS tagging have omitted details of the suffix analysis used for handling unknown
      words. The suffix of an English word is a strong predictor of a POS tag for that
      word. As a pre-requisite for an accurate HMM POS tagger for biomedical
      publications, we present an efficient suffix prediction method for integration
      into a POS tagger. RESULTS: We have implemented a fully functional HMM POS tagger
      using experimentally optimised suffix based prediction. Our simple suffix
      analysis method, significantly outperformed the probability interpolation based
      TnT method. We have also shown how important suffix analysis can be for
      probability estimation of a known word (in the training corpus) with an unseen
      POS tag; a common scenario with a small training corpus. We then integrated this
      simple method in our POS tagger and determined an optimised parameter set for
      both methods, which can help developers to optimise their current algorithm,
      based on our results. We also introduce the concept of counting methods in
      maximum likelihood estimation for the first time and show how counting methods
      can affect the prediction result. Finally, we describe how machine-learning
      techniques were applied to identify words, for which prediction of POS tags were
      always incorrect and propose a method to handle words of this type. AVAILABILITY
      AND IMPLEMENTATION: Java source code, binaries and setup instructions are freely
      available at http://genomes.sapac.edu.au/text_mining/pos_tagger.zip.

PMID- 24124533
TI  - Understanding recurrent crime as system-immanent collective behavior.
AB  - Containing the spreading of crime is a major challenge for society. Yet, since
      thousands of years, no effective strategy has been found to overcome crime. To
      the contrary, empirical evidence shows that crime is recurrent, a fact that is
      not captured well by rational choice theories of crime. According to these,
      strong enough punishment should prevent crime from happening. To gain a better
      understanding of the relationship between crime and punishment, we consider that
      the latter requires prior discovery of illicit behavior and study a spatial
      version of the inspection game. Simulations reveal the spontaneous emergence of
      cyclic dominance between "criminals", "inspectors", and "ordinary people" as a
      consequence of spatial interactions. Such cycles dominate the evolutionary
      process, in particular when the temptation to commit crime or the cost of
      inspection are low or moderate. Yet, there are also critical parameter values
      beyond which cycles cease to exist and the population is dominated either by a
      stable mixture of criminals and inspectors or one of these two strategies alone.
      Both continuous and discontinuous phase transitions to different final states are
      possible, indicating that successful strategies to contain crime can be very much
      counter-intuitive and complex. Our results demonstrate that spatial interactions
      are crucial for the evolutionary outcome of the inspection game, and they also
      reveal why criminal behavior is likely to be recurrent rather than evolving
      towards an equilibrium with monotonous parameter dependencies. 

PMID- 24124534
TI  - The role and dynamics of beta-catenin in precondition induced neuroprotection
      after traumatic brain injury.
AB  - Preconditioning via heat acclimation (34 degrees C 30 d) results in
      neuroprotection from traumatic brain injury due to constitutive as well as
      dynamic changes triggered by the trauma. Among these changes is Akt
      phosphorylation, which decreases apoptosis and induces HIF1alpha. In the present
      study we investigated the Akt downstream GSK3beta/beta-catenin pathway and
      focused on post injury alternations of beta catenin and its impact on the
      cellular response in preconditioned heat acclimated mice. We found that the
      reduction in motor disability is accompanied with attenuation of depressive like
      behavior in heat acclimated mice that correlates with the GSK3beta
      phosphorylation state. Concomitantly, a robust beta catenin phosphorylation is
      not followed by its degradation, or by reduced nuclear accumulation. Enhanced
      tyrosine phosphorylation of beta catenin in the injured area weakens the beta
      catenin-N cadherin complex. Membrane beta catenin is transiently reduced in heat
      acclimated mice and its recovery 7 days post TBI is accompanied by induction of
      the synaptic marker synaptophysin. We suggest a set of cellular events following
      traumatic brain injury in heat acclimated mice that causes beta catenin to
      participate in cell-cell adhesion alternations rather than in Wnt signaling.
      These events may contribute to synaptogenesis and the improved motor and
      cognitive abilities seen heat acclimated mice after traumatic brain injury.

PMID- 24124535
TI  - Relationship between NaCl- and H2O2-induced cytosolic Ca2+ increases in response
      to stress in Arabidopsis.
AB  - Salinity is among the environmental factors that affect plant growth and
      development and constrain agricultural productivity. Salinity stress triggers
      increases in cytosolic free Ca(2+) concentration ([Ca(2+)]i) via Ca(2+) influx
      across the plasma membrane. Salinity stress, as well as other stresses, induces
      the production of reactive oxygen species (ROS). It is well established that ROS
      also triggers increases in [Ca(2+)]i. However, the relationship and interaction
      between salinity stress-induced [Ca(2+)]i increases and ROS-induced [Ca(2+)]i
      increases remain poorly understood. Using an aequorin-based Ca(2+) imaging assay
      we have analyzed [Ca(2+)]i changes in response to NaCl and H2O2 treatments in
      Arabidopsis thaliana. We found that NaCl and H2O2 together induced larger
      increases in [Ca(2+)]i in Arabidopsis seedlings than either NaCl or H2O2 alone,
      suggesting an additive effect on [Ca(2+)]i increases. Following a pre-treatment
      with either NaCl or H2O2, the subsequent elevation of [Ca(2+)]i in response to a
      second treatment with either NaCl or H2O2 was significantly reduced. Furthermore,
      the NaCl pre-treatment suppressed the elevation of [Ca(2+)]i seen with a second
      NaCl treatment more than that seen with a second treatment of H2O2. A similar
      response was seen when the initial treatment was with H2O2; subsequent addition
      of H2O2 led to less of an increase in [Ca(2+)]i than did addition of NaCl. These
      results imply that NaCl-gated Ca(2+) channels and H2O2-gated Ca(2+) channels may
      differ, and also suggest that NaCl- and H2O2-evoked [Ca(2+)]i may reduce the
      potency of both NaCl and H2O2 in triggering [Ca(2+)]i increases, highlighting a
      feedback mechanism. Alternatively, NaCl and H2O2 may activate the same Ca(2+)
      permeable channel, which is expressed in different types of cells and/or
      activated via different signaling pathways. 

PMID- 24124536
TI  - Predicting visual consciousness electrophysiologically from intermittent
      binocular rivalry.
AB  - PURPOSE: We sought brain activity that predicts visual consciousness. METHODS: We
      used electroencephalography (EEG) to measure brain activity to a 1000-ms display
      of sine-wave gratings, oriented vertically in one eye and horizontally in the
      other. This display yields binocular rivalry: irregular alternations in visual
      consciousness between the images viewed by the eyes. We replaced both gratings
      with 200 ms of darkness, the gap, before showing a second display of the same
      rival gratings for another 1000 ms. We followed this by a 1000-ms mask then a
      2000-ms inter-trial interval (ITI). Eleven participants pressed keys after the
      second display in numerous trials to say whether the orientation of the visible
      grating changed from before to after the gap or not. Each participant also
      responded to numerous non-rivalry trials in which the gratings had identical
      orientations for the two eyes and for which the orientation of both either
      changed physically after the gap or did not. RESULTS: We found that greater
      activity from lateral occipital-parietal-temporal areas about 180 ms after
      initial onset of rival stimuli predicted a change in visual consciousness more
      than 1000 ms later, on re-presentation of the rival stimuli. We also found that
      less activity from parietal, central, and frontal electrodes about 400 ms after
      initial onset of rival stimuli predicted a change in visual consciousness about
      800 ms later, on re-presentation of the rival stimuli. There was no such
      predictive activity when the change in visual consciousness occurred because the
      stimuli changed physically. CONCLUSION: We found early EEG activity that
      predicted later visual consciousness. Predictive activity 180 ms after onset of
      the first display may reflect adaption of the neurons mediating visual
      consciousness in our displays. Predictive activity 400 ms after onset of the
      first display may reflect a less-reliable brain state mediating visual
      consciousness.

PMID- 24124537
TI  - MURF2B, a novel LC3-binding protein, participates with MURF2A in the switch
      between autophagy and ubiquitin proteasome system during differentiation of C2C12
      muscle cells.
AB  - The ubiquitin proteasome system and macroautophagy are proteolytic pathways
      essential in the maintenance of cellular homeostasis during differentiation and
      remodelling of skeletal muscle. In both pathways, proteins to be degraded are
      tagged with polyubiquitin. In skeletal muscles, the MURF2 proteins display E3
      ubiquitin ligase structure suggesting that they may covalently attach ubiquitin
      polypeptides to still unknown target proteins. So far only MURF2A isoforms were
      studied and shown to interact with p62/SQSTM1, a protein implicated in
      macroautophagic and ubiquitin proteasome system degradations. Here, we analyzed
      the MURF2B and MURF2A proteins and show that the ratio of the isoforms changes
      during differentiation of muscle C2C12 cells and that the shift of the isoforms
      expression follows the sequential activation of autophagic or proteasomal
      degradation. We also show that MURF2B has a functional domain needed for its
      interaction with LC3, a protein needed for autophagic vesicles formation. Using
      specific MURF2 RNAi cells we observed that MURF2A and MURF2B are both needed for
      the formation of autophagosomes and that in the absence of MURF2B, the cells
      expressing MURF2A display an activated ubiquitin proteasome system implicated in
      the degradation of p62/SQSTM1 by UPS. Altogether, our results indicate that
      MURF2A and MURF2B proteins could participate in the molecular switch between the
      two ubiquitin degradative pathways. 

PMID- 24124538
TI  - Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian
      ethnicity.
AB  - BACKGROUND: During the past decade, the incidence of EGFR mutation has been shown
      to vary across different ethnicities. It occurs at the rate of 10-15% in North
      Americans and Europeans, 19% in African-Americans, 20-30% in various East Asian
      series including Chinese, Koreans, and Japanese. Frequency of EGFR mutations in
      India however remains sparsely explored. METHODOLOGY/PRINCIPAL FINDINGS: We
      report 23% incidence of Epidermal growth factor receptor (EGFR) mutations in 907
      Non small cell lung cancer (NSCLC) patients of Indian ethnicity, in contrast to
      10-15% known in Caucasians and 27-62% among East Asians. In this study, EGFR
      mutations were found to be more common in never-smokers 29.4% as compared to
      smokers 15.3%. Consistent with other populations, mutation rates among
      adenocarcinoma-males were predominantly lower than females with 32% incidence.
      However unlike Caucasians, EGFR mutation rate among adenocarcinoma-never-smoker
      females were comparable to males suggesting lack of gender bias among never
      smokers likely to benefit from EGFR targeted therapy. CONCLUSIONS/SIGNIFICANCE:
      This study has an overall implication for establishing relevance for routine EGFR
      mutation diagnostics for NSCLC patients in clinics and emphasizes effectiveness
      for adoption of EGFR inhibitors as the first line treatment among Indian
      population. The intermediate frequency of EGFR mutation among Indian population
      compared to Caucasians and East Asians is reminiscent of an ancestral admixture
      of genetic influence from Middle Easterners, Central Asians, and Europeans on
      modern- Indian population that may confer differential susceptibility to somatic
      mutations in EGFR.

PMID- 24124540
TI  - In vivo evaluation of immediately loaded stainless steel and titanium orthodontic
      screws in a growing bone.
AB  - The present work intends to evaluate the use of immediate loaded orthodontic
      screws in a growing model, and to study the specific bone response. Thirty-two
      screws (half of stainless steel and half of titanium) were inserted in the
      alveolar bone of 8 growing pigs. The devices were immediately loaded with a 100 g
      orthodontic force. Two loading periods were assessed: 4 and 12 weeks. Both
      systems of screws were clinically assessed. Histological observations and
      histomorphometric analysis evaluated the percent of "bone-to-implant contact" and
      static and dynamic bone parameters in the vicinity of the devices (test zone) and
      in a bone area located 1.5 cm posterior to the devices (control zone). Both
      systems exhibit similar responses for the survival rate; 87.5% and 81.3% for
      stainless steel and titanium respectively (p = 0.64; 4-week period), and 62.5%
      and 50.0% for stainless steel and titanium respectively (p = 0.09; 12-week
      period). No significant differences between the devices were found regarding the
      percent of "bone-to-implant contact" (p = 0.1) or the static and dynamic bone
      parameters. However, the 5% threshold of "bone-to-implant contact" was obtained
      after 4 weeks with the stainless steel devices, leading to increased survival
      rate values. Bone in the vicinity of the miniscrew implants showed evidence of a
      significant increase in bone trabecular thickness when compared to bone in the
      control zone (p = 0.05). In our study, it is likely that increased trabecular
      thickness is a way for low density bone to respond to the stress induced by
      loading. 

PMID- 24124539
TI  - The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent
      fusion mediated by class II and III viral proteins.
AB  - Voltage dependence of fusion induced by class II and class III viral fusion
      proteins was investigated. Class II proteins from Ross River and Sindbus virus
      and a mutant class III protein from Epstein Barr virus were found to induce cell
      cell fusion that is voltage dependent. Combined with previous studies, in all,
      four class II and two class III protein have now been shown to exhibit voltage
      dependent fusion, demonstrating that this is probably a general phenomenon for
      these two classes of viral fusion proteins. In the present study, monitoring
      fusion of pseudovirus expressing Vesicular Stomatitis virus (VSV) G within
      endosomes shows that here, too, fusion is voltage dependent. This supports the
      claim that voltage dependence of fusion is biologically relevant and that cell
      cell fusion reliably models the voltage dependence. Fusion induced by class I
      viral proteins is independent of voltage; chimeras expressing the ectodomain of a
      class I fusion protein and the transmembrane domain of VSV G could therefore be
      used to explore the location within the protein responsible for voltage
      dependence. Results showed that the transmembrane domain is the region associated
      with voltage dependence. Experiments in which cells were enriched with acidic
      lipids led to the conclusion that it is the flip-flop of acidic lipids that
      carries the charge responsible for the observed voltage dependence of fusion.
      This flip-flop occurred downstream of hemifusion, in accord with previous
      findings that the voltage dependent steps of fusion occur at a stage subsequent
      to hemifusion. 

PMID- 24124541
TI  - Habitat fragmentation and ecological traits influence the prevalence of avian
      blood parasites in a tropical rainforest landscape.
AB  - In the tropical rainforests of northern Australia, we investigated the effects of
      habitat fragmentation and ecological parameters on the prevalence of blood-borne
      parasites (Plasmodium and Haemoproteus) in bird communities. Using mist-nets on
      forest edges and interiors, we sampled bird communities across six study sites: 3
      large fragments (20-85 ha) and 3 continuous-forest sites. From 335 mist-net
      captures, we recorded 28 bird species and screened 299 bird samples with PCR to
      amplify and detect target DNA. Of the 28 bird species sampled, 19 were infected
      with Plasmodium and/or Haemoproteus and 9 species were without infection. Over
      one third of screened birds (99 individuals) were positive for Haemoproteus
      and/or Plasmodium. In forest fragments, bird capture rates were significantly
      higher than in continuous forests, but bird species richness did not differ.
      Unexpectedly, we found that the prevalence of the dominant haemosporidian
      infection, Haemoproteus, was significantly higher in continuous forest than in
      habitat fragments. Further, we found that ecological traits such as diet,
      foraging height, habitat specialisation and distributional ranges were
      significantly associated with blood-borne infections. 

PMID- 24124542
TI  - Elevated paracellular glucose flux across cystic fibrosis airway epithelial
      monolayers is an important factor for Pseudomonas aeruginosa growth.
AB  - People with cystic fibrosis (CF) who develop related diabetes (CFRD) have
      accelerated pulmonary decline, increased infection with antibiotic-resistant
      Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously
      shown that glucose concentrations are elevated in airway surface liquid (ASL) of
      people with CF, particularly in those with CFRD. We therefore explored the
      hypotheses that glucose homeostasis is altered in CF airway epithelia and that
      elevation of glucose flux into ASL drives increased bacterial growth, with an
      effect over and above other cystic fibrosis transmembrane conductance regulator
      (CFTR)-related ASL abnormalities. The aim of this study was to compare the
      mechanisms governing airway glucose homeostasis in CF and non-CF primary human
      bronchial epithelial (HBE) monolayers, under normal conditions and in the
      presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in
      the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in
      blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth.
      Calu-3 cell monolayers were used to evaluate the potential importance of glucose
      on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely
      mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that
      elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on
      CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa
      secretions elicited more glucose flux across CF airway epithelial monolayers
      compared to non-CF monolayers which we propose increases glucose availability in
      ASL for bacterial growth. In addition, elevating basolateral glucose increased
      Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence
      or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together
      these studies highlight the importance of glucose as an additional factor in
      promoting Ps. aeruginosa growth and respiratory infection in CF disease. 

PMID- 24124544
TI  - The "Alluvial Mesovoid Shallow Substratum", a new subterranean habitat.
AB  - In this paper we describe a new type of subterranean habitat associated with dry
      watercourses in the Eastern Iberian Peninsula, the "Alluvial Mesovoid Shallow
      Substratum" (alluvial MSS). Historical observations and data from field sampling
      specially designed to study MSS fauna in the streambeds of temporary watercourses
      support the description of this new habitat. To conduct the sampling, 16
      subterranean sampling devices were placed in a region of Eastern Spain. The traps
      were operated for 12 months and temperature and relative humidity data were
      recorded to characterise the habitat. A large number of species was captured,
      many of which belonged to the arthropod group, with marked hygrophilous,
      geophilic, lucifugous and mesothermal habits. In addition, there was also a
      substantial number of species showing markedly ripicolous traits. The results
      confirm that the network of spaces which forms in alluvial deposits of temporary
      watercourses merits the category of habitat, and here we propose the name of
      "alluvial MSS". The "alluvial MSS" may be covered or not by a layer of soil, is
      extremely damp, provides a buffer against above ground temperatures and is
      aphotic. In addition, compared to other types of MSS, it is a very unstable
      habitat. It is possible that the "alluvial MSS" may be found in other areas of
      the world with strongly seasonal climatic regimes, and could play an important
      role as a biogeographic corridor and as a refuge from climatic changes.

PMID- 24124543
TI  - Pneumococcal carriage in young children one year after introduction of the 13
      valent conjugate vaccine in Italy.
AB  - BACKGROUND: In mid 2010, the 7-valent pneumococcal conjugate vaccine (PCV7) was
      replaced by the 13-valent conjugate vaccine (PCV13) for childhood immunization in
      Italy. Our objective in this study was to obtain a snapshot of pneumococcal
      carriage frequency, colonizing serotypes, and antibiotic resistance in healthy
      children in two Italian cities one year after PCV13 was introduced. METHODS:
      Nasopharyngeal swabs were obtained from 571 children aged 0-5 years from November
      2011-April 2012. Pneumococcal isolates were serotyped and tested for
      antimicrobial susceptibility. Penicillin and/or erythromycin non-susceptible
      isolates were analyzed by Multi Locus Sequence Typing (MLST). RESULTS: Among the
      children examined, 81.2% had received at least one dose of PCV7 or PCV13 and
      74.9% had completed the recommended vaccination schedule for their age. Among the
      latter, 57.3% of children had received PCV7, 27.1% PCV13, and 15.6% a combination
      of the two vaccines. The overall carriage rate was 32.9%, with children aged 6-35
      months the most prone to pneumococcal colonization (6-23 months OR: 3.75; 95% CI:
      2.19-6.43 and 24-35 months OR: 3.15, 95%CI: 2.36-4.22). A total of 184
      pneumococcal isolates were serotyped and divided into PCV7 (5.4%), PCV13 (18.0%),
      and non-PCV13 (82.0%) serotypes. Serotypes 6C, 24F, and 19A were the most
      prevalent (10.3%, 8.6%, and 8.1%, respectively). The proportion of penicillin non
      susceptible (MIC >0.6 mg/L) isolates was 30.9%, while 42.3% were erythromycin
      resistant. Non-PCV13 serotypes accounted for 75.4% and 70.8% of the penicillin
      and erythromycin non-susceptible isolates, respectively. CONCLUSIONS: Our results
      revealed low rates of PCV7 and PCV13 serotypes in Italian children, potentially
      due to the effects of vaccination. As the use of PCV13 continues, its potential
      impact on vaccine serotypes such as 19A and cross-reactive serotypes such as 6C
      will be assessed, with this study providing a baseline for further analysis of
      surveillance isolates.

PMID- 24124545
TI  - Global and 3D spatial assessment of neuroinflammation in rodent models of
      Multiple Sclerosis.
AB  - Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and
      demyelinating disease of the central nervous system (CNS). T cells play a key
      role in the progression of neuroinflammation in MS and also in the experimental
      autoimmune encephalomyelitis (EAE) animal models for the disease. A technology
      for quantitative and 3 dimensional (3D) spatial assessment of inflammation in
      this and other CNS inflammatory conditions is much needed. Here we present a
      procedure for 3D spatial assessment and global quantification of the development
      of neuroinflammation based on Optical Projection Tomography (OPT). Applying this
      approach to the analysis of rodent models of MS, we provide global quantitative
      data of the major inflammatory component as a function of the clinical course.
      Our data demonstrates a strong correlation between the development and
      progression of neuroinflammation and clinical disease in several mouse and a rat
      model of MS refining the information regarding the spatial dynamics of the
      inflammatory component in EAE. This method provides a powerful tool to
      investigate the effect of environmental and genetic forces and for assessing the
      therapeutic effects of drug therapy in animal models of MS and other
      neuroinflammatory/neurodegenerative disorders. 

PMID- 24124546
TI  - MLVA genotyping of Brucella melitensis and Brucella abortus isolates from
      different animal species and humans and identification of Brucella suis vaccine
      strain S2 from cattle in China.
AB  - In China, brucellosis is an endemic disease and the main sources of brucellosis
      in animals and humans are infected sheep, cattle and swine. Brucella melitensis
      (biovars 1 and 3) is the predominant species, associated with sporadic cases and
      outbreak in humans. Isolates of B. abortus, primarily biovars 1 and 3, and B.
      suis biovars 1 and 3 are also associated with sporadic human brucellosis. In this
      study, the genetic profiles of B. melitensis and B. abortus isolates from humans
      and animals were analyzed and compared by multi-locus variable-number tandem
      repeat analysis (MLVA). Among the B. melitensis isolates, the majority (74/82)
      belonged to MLVA8 genotype 42, clustering in the 'East Mediterranean' group. Two
      B. melitensis biovar 1 genotype 47 isolates, belonging to the 'Americas' group,
      were recovered; both were from the Himalayan blue sheep (Pseudois nayaur, a wild
      animal). The majority of B. abortus isolates (51/70) were biovar 3, genotype 36.
      Ten B. suis biovar 1 field isolates, including seven outbreak isolates recovered
      from a cattle farm in Inner Mongolia, were genetically indistinguishable from the
      vaccine strain S2, based on MLVA cluster analysis. MLVA analysis provided
      important information for epidemiological trace-back. To the best of our
      knowledge, this is the first report to associate Brucella cross-infection with
      the vaccine strain S2 based on molecular comparison of recovered isolates to the
      vaccine strain. MLVA typing could be an essential assay to improve brucellosis
      surveillance and control programs. 

PMID- 24124547
TI  - Alterations of tear mediators in patients with keratoconus after corneal
      crosslinking associate with corneal changes.
AB  - Keratoconus (KC) is the most common primary corneal ectatic disease which has
      considerable importance in public health. Corneal collagen crosslinking (CXL) is
      a procedure to mitigate progression of KC and reduce demand for corneal
      transplantation. Although studies have proven the efficacy of CXL regarding
      corneal shape, none have investigated the effects of CXL on tear biomarkers which
      are useful tools to understand molecular mechanisms behind CXL. Our purpose was
      to determine the effect of CXL on tear mediators in patients with KC and analyze
      associations with corneal changes. Tear samples were collected pre-CXL from 26
      eyes of 23 patients and during a 12-month follow-up. The mediators' concentration
      was measured by Cytometric Bead Array technology. Corneal topography parameters
      measured by Scheimpflug Camera included: Thinnest-corneal-thickness (ThCT),
      keratometry values (K1, K2), Radii-Minimum (Rmin), Keratoconus-Index (KI), Center
      KI (CKI), Index-of-Height Asymmetry (IHA) and Index-of-Surface Variance (ISV). At
      baseline, KI was correlated negatively with chemokine (C-C motif) ligand 5 (CCL5)
      (p=0.015) and matrix metalloproteinase (MMP)-13 (p=0.007). At day 4, interleukin
      (IL)-6 and IL-8 increased, while IL-13, IL-17A, interferon (IFN)-gamma, CCL5, MMP
      13, epidermal growth factor (EGF), nerve growth factor (NGF) and plasminogen
      activator inhibitor (PAI-1) decreased significantly compared to pre-CXL
      concentrations (p<=0.02). At 6 months tissue plasminogen activator (t-PA)
      increased (p=0.02), while at 12 months Rmin increased (p<=0.004), and IL-6 and
      CXCL8 (p=0.005 and p=0.047) as well as K1, ISV and KI decreased. After 6 months
      CKI and ISV showed significant associations with IL-17A; CKI with IL-13 and ThCT
      with IL-13 (p<=0.02), while at 12 months there were reverse associations between
      ThCT and IL-6, IL-13, INFgamma, CCL5 and PAI-1 (p<=0.02). Alterations of
      mediators in tear fluid after CXL associate with topographic changes highlight
      the fact that many mediators are involved in the complex mechanisms after CXL.
      Further studies on biomarkers to investigate the efficacy of CXL are needed.

PMID- 24124548
TI  - Association between adherence to nutritional guidelines, the metabolic syndrome
      and adiposity markers in a French adult general population.
AB  - INTRODUCTION: Few studies have focused on the association between diet quality
      scores and the Metabolic Syndrome (MetS), a multi-component condition predictive
      of cardiovascular diseases (CVD) and death. The present study aims at
      investigating, in a cross-sectional design, the association between adherence to
      the French dietary guidelines through an a priori score - the French Nutrition
      and Health Program-Guideline Score (PNNS-GS) - and cardiovascular risk factors
      (CVRF) including the MetS and adiposity markers. METHODS: 7902 French adults
      participating in the NutriNet-Sante study (an on-going web-based cohort study)
      attended a clinical and biological examination between January 2011 and November
      2012: a fasting blood sample was drawn, blood pressure and body composition (bio
      impedance) were measured. Multivariate linear and logistic regression models were
      used to assess the association between PNNS-GS and CVRF or the MetS. RESULTS: An
      increase of PNNS-GS was significantly negatively associated with waist
      circumference (WC), systolic and diastolic blood pressure (SBP and DBP) and serum
      triglycerides concentrations. From bottom to top quartile of PNNS-GS, SBP
      decreased from 129.9 to 128.8 mm Hg, DBP from 76.7 to 75.9 mm Hg, serum
      triglycerides concentrations from 110.8 to 104.6 mg/dL and WC from 94.8 to 90.1
      cm for men and 81.3 to 78.9 cm for women. All adiposity markers (waist and hip
      circumference, % body fat, % trunk fat, % leg fat) were markedly reduced across
      quartiles of PNNS-GS and linearly. Individuals with a better PNNS-GS (quartile 4
      vs quartile 1) were less likely to have the MetS (OR=0.71, 95% CI: 0.56-0.89).
      CONCLUSION: The negative association between a higher adherence to the French
      dietary guidelines and a number of CVRF, the MetS prevalence and regional
      adiposity supports the importance of promoting the PNNS dietary guidelines in the
      population for the prevention of cardiometabolic abnormalities and hence,
      cardiovascular diseases.

PMID- 24124549
TI  - Yoga for essential hypertension: a systematic review.
AB  - BACKGROUND: Yoga is thought to be effective for health conditions. The article
      aims to assess the current clinical evidence of yoga for Essential hypertension
      (EH). STRATEGY: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled
      Trials (CENTRAL) in the Cochrane Library were searched until June, 2013. We
      included randomized clinical trials testing yoga against conventional therapy,
      yoga versus no treatment, yoga combined with conventional therapy versus
      conventional therapy or conventional therapy combined with breath awareness.
      Study selection, data extraction, quality assessment, and data analyses were
      conducted according to the Cochrane standards. RESULTS: A total of 6 studies
      (involving 386 patients) were included. The methodological quality of the
      included trials was evaluated as generally low. A total of 6 RCTs met all the
      inclusion criteria. 4 of them compared yoga plus conventional therapy with
      conventional therapy. 1 RCT described yoga combined with conventional therapy
      versus conventional therapy combined with breath awareness. 2 RCT tested the
      effect of yoga versus conventional therapy alone. 1 RCT described yoga compared
      to no treatment. Only one trial reported adverse events without details, the
      safety of yoga is still uncertain. CONCLUSIONS: There is some encouraging
      evidence of yoga for lowering SBP and DBP. However, due to low methodological
      quality of these identified trials, a definite conclusion about the efficacy and
      safety of yoga on EH cannot be drawn from this review. Therefore, further
      thorough investigation, large-scale, proper study designed, randomized trials of
      yoga for hypertension will be required to justify the effects reported here.

PMID- 24124550
TI  - Understanding the impact of 2D and 3D fibroblast cultures on in vitro breast
      cancer models.
AB  - The utilization of 3D, physiologically relevant in vitro cancer models to
      investigate complex interactions between tumor and stroma has been increasing.
      Prior work has generally focused on the cancer cells and, the role of fibroblast
      culture conditions on tumor-stromal cell interactions is still largely unknown.
      Here, we focus on the stroma by comparing functional behaviors of human mammary
      fibroblasts (HMFs) cultured in 2D and 3D and their effects on the invasive
      progression of breast cancer cells (MCF10DCIS.com). We identified increased
      levels of several paracrine factors from HMFs cultured in 3D conditions that
      drive the invasive transition. Using a microscale co-culture model with improved
      compartmentalization and sensitivity, we demonstrated that HMFs cultured in 3D
      intensify the promotion of the invasive progression through the HGF/c-Met
      interaction. This study highlights the importance of the 3D stromal
      microenvironment in the development of multiple cell type in vitro cancer models.

PMID- 24124551
TI  - Physiological and morphological responses of the temperate seagrass Zostera
      muelleri to multiple stressors: investigating the interactive effects of light
      and temperature.
AB  - Understanding how multiple environmental stressors interact to affect seagrass
      health (measured as morphological and physiological responses) is important for
      responding to global declines in seagrass populations. We investigated the
      interactive effects of temperature stress (24, 27, 30 and 32 degrees C) and
      shading stress (75, 50, 25 and 0% shade treatments) on the seagrass Zostera
      muelleri over a 3-month period in laboratory mesocosms. Z. muelleri is widely
      distributed throughout the temperate and tropical waters of south and east coasts
      of Australia, and is regarded as a regionally significant species. Optimal growth
      was observed at 27 degrees C, whereas rapid loss of living shoots and leaf mass
      occurred at 32 degrees C. We found no difference in the concentration of
      photosynthetic pigments among temperature treatments by the end of the
      experiment; however, up-regulation of photoprotective pigments was observed at 30
      degrees C. Greater levels of shade resulting in high photochemical efficiencies,
      while elevated irradiance suppressed effective quantum yield (DeltaF/FM').
      Chlorophyll fluorescence fast induction curves (FIC) revealed that the J step
      amplitude was significantly higher in the 0% shade treatment after 8 weeks,
      indicating a closure of PSII reaction centres, which likely contributed to the
      decline in DeltaF/FM' and photoinhibition under higher irradiance. Effective
      quantum yield of PSII (DeltaF/FM') declined steadily in 32 degrees C treatments,
      indicating thermal damage. Higher temperatures (30 degrees C) resulted in reduced
      above-ground biomass ratio and smaller leaves, while reduced light led to a
      reduction in leaf and shoot density, above-ground biomass ratio, shoot biomass
      and an increase in leaf senescence. Surprisingly, light and temperature had few
      interactive effects on seagrass health, even though these two stressors had
      strong effects on seagrass health when tested in isolation. In summary, these
      results demonstrate that populations of Z. muelleri in south-eastern Australia
      are sensitive to small chronic temperature increases and light decreases that are
      predicted under future climate change scenarios.

PMID- 24124552
TI  - The impact of fish predation and cyanobacteria on zooplankton size structure in
      96 subtropical lakes.
AB  - Zooplankton are relatively small in size in the subtropical regions. This
      characteristic has been attributed to intense predation pressure, high nutrient
      loading and cyanobacterial biomass. To provide further information on the effect
      of predation and cyanobacteria on zooplankton size structure, we analyzed data
      from 96 shallow aquaculture lakes along the Yangtze River. Contrary to former
      studies, both principal components analysis and multiple regression analysis
      showed that the mean zooplankton size was positively related to fish yield. The
      studied lakes were grouped into three types, namely, natural fishing lakes with
      low nutrient loading (Type1), planktivorous fish-dominated lakes (Type 2), and
      eutrophic lakes with high cyanobacterial biomass (Type 3). A marked difference in
      zooplankton size structure was found among these groups. The greatest mean
      zooplankton size was observed in Type 2 lakes, but zooplankton density was the
      lowest. Zooplankton abundance was highest in Type 3 lakes and increased with
      increasing cyanobacterial biomass. Zooplankton mean size was negatively
      correlated with cyanobacterial biomass. No obvious trends were found in Type 1
      lakes. These results were reflected by the normalized biomass size spectrum,
      which showed a unimodal shape with a peak at medium sizes in Type 2 lakes and a
      peak at small sizes in Type 3 lakes. These results indicated a relative increase
      in medium-sized and small-sized species in Types 2 and 3 lakes, respectively. Our
      results suggested that fish predation might have a negative effect on zooplankton
      abundance but a positive effect on zooplankton size structure. High
      cyanobacterial biomass most likely caused a decline in the zooplankton size and
      encouraged the proliferation of small zooplankton. We suggest that both
      planktivorous fish and cyanobacteria have substantial effects on the shaping of
      zooplankton community, particularly in the lakes in the eastern plain along the
      Yangtze River where aquaculture is widespread and nutrient loading is high.

PMID- 24124553
TI  - Tumor secretion of CCL22 activates intratumoral Treg infiltration and is
      independent prognostic predictor of breast cancer.
AB  - It has been reported that dense intratumoral infiltration of Foxp3 (+)Tregs
      (Tregs) was an independent factor for poor prognosis of breast cancer (BC)
      patients. However, the cytokines activating the Treg infiltration are not known.
      This study was undertaken to evaluate the role of CCL22 and TGF-beta1 in this
      cascade and their prognostic significance for BC patients. 417 cases of invasive
      breast cancer were selected from the prior study cohort and the expressions of
      CCL22 and TGF-beta1 were assessed by immunohistochemistry. It was identified that
      tumor secretion of CCL22 was positively correlated with the intratumoral Treg
      infiltration (P<0.0001), but its association with lymphoid aggregates surrounding
      the tumor was not proven to be significant (P=0.056). Moreover, CCL22 expression
      was found to be associated with the tumor histological features known to be
      related with unfavorable prognosis of patients, including high histological grade
      (P<0.0001), negative ER (P<0.0001), negative PR (P=0.001), and HER2 amplification
      (P=0.028). Similar to intratumoral Treg infiltrates, CCL22 tumor secretion
      correlated with the prognosis of the molecular subtypes of breast carcinoma
      (P<0.0001). Univariate analysis revealed CCL22 to be an independent prognostic
      factor for overall survival (OS, P<0.0001) and progression-free survival (PFS,
      P<0.0001) of BC patients that were confirmed by multivariate analysis (P=0.011
      and P=0.010 respectively). In contrast, although TGF-beta1 expression was
      positively correlated with both Tregs infiltrates into the tumor bed and lymphoid
      aggregates surrounding the tumor (P=0.023; P=0.046, respectively), its expression
      was not significantly associated with the molecular subtypes of breast carcinoma
      and the prognosis of the patients. Our study indicates that both CCL22 and TGF
      beta1 are candidate chemoattractants for intratumoral Foxp3 (+)Tregs
      infiltration; however, unlike the later, CCL22 is an independent prognostic
      predictor of BC patients, and it therefore may have the potential to serve as a
      target for immunotherapeutic strategy of BC.

PMID- 24124554
TI  - Fluctuating vs. continuous exposure to H2O2: the effects on mitochondrial
      membrane potential, intracellular calcium, and NF-kappaB in astroglia.
AB  - The effects of H2O2 are widely studied in cell cultures and other in vitro
      systems. However, such investigations are performed with the assumption that H2O2
      concentration is constant, which may not properly reflect in vivo settings,
      particularly in redox-turbulent microenvironments such as mitochondria. Here we
      introduced and tested a novel concept of fluctuating oxidative stress. We treated
      C6 astroglial cells and primary astrocytes with H2O2, using three regimes of
      exposure - continuous, as well as fluctuating at low or high rate, and evaluated
      mitochondrial membrane potential and other parameters of mitochondrial activity -
      respiration, reducing capacity, and superoxide production, as well as
      intracellular ATP, intracellular calcium, and NF-kappaB activation. When compared
      to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization
      in mitochondria, whereas the activity of electron transport chain appears not to
      be significantly affected. H2O2 provoked a decrease of ATP level and an increase
      of intracellular calcium concentration, independently of the regime of treatment.
      However, fluctuating H2O2 induced a specific pattern of large-amplitude
      fluctuations of calcium concentration. An impact on NF-kappaB activation was
      observed for high rate fluctuations, whereas continuous and low rate fluctuating
      oxidative stress did not provoke significant effects. Presented results outline
      the (patho)physiological relevance of redox fluctuations. 

PMID- 24124555
TI  - Monitoring Hip and Elbow Dysplasia achieved modest genetic improvement of 74 dog
      breeds over 40 years in USA.
AB  - Hip (HD) and Elbow Dysplasia (ED) are two common complex developmental disorders
      of dogs. In order to decrease their prevalence and severity, the Orthopedic
      Foundation for Animals (OFA) has a voluntary registry of canine hip and elbow
      conformation certified by boarded radiologists. However, the voluntarily reports
      have been severely biased against exposing dogs with problems, especially at
      beginning period. Fluctuated by additional influential factors such as age, the
      published raw scores barely showed trends of improvement. In this study, we used
      multiple-trait mixed model to simultaneously adjust these factors and incorporate
      pedigree to derive Estimated Breeding Values (EBV). A total of 1,264,422 dogs
      from 74 breeds were evaluated for EBVs from 760,455 hip scores and 135,409 elbow
      scores. These EBVs have substantially recovered the reporting bias and the other
      influences. Clear and steady trends of genetic improvement were observed over the
      40 years since 1970. The total genetic improvements were 16.4% and 1.1% of the
      phenotypic standard deviation for HD and ED, respectively. The incidences of
      dysplasia were 0.83% and 2.08%, and the heritabilities were estimated as 0.22 and
      0.17 for hip and elbow scores, respectively. The genetic correlation between them
      was 0.12. We conclude that EBV is more effective than reporting raw phenotype.
      The weak genetic correlation suggested that selection based on hip scores would
      also slightly improve elbow scores but it is necessary to allocate effort toward
      improvement of elbow scores alone. 

PMID- 24124556
TI  - Comprehensive mapping of regional expression of the clock protein PERIOD2 in rat
      forebrain across the 24-h day.
AB  - In mammals, a light-entrainable clock located in the suprachiasmatic nucleus
      (SCN) regulates circadian rhythms by synchronizing oscillators throughout the
      brain and body. Notably, the nature of the relation between the SCN clock and
      subordinate oscillators in the rest of the brain is not well defined. We
      performed a high temporal resolution analysis of the expression of the circadian
      clock protein PERIOD2 (PER2) in the rat forebrain to characterize the
      distribution, amplitude and phase of PER2 rhythms across different regions.
      Eighty-four LEW/Crl male rats were entrained to a 12-h: 12-h light/dark cycle,
      and subsequently perfused every 30 min across the 24-h day for a total of 48 time
      points. PER2 expression was assessed with immunohistochemistry and analyzed using
      automated cell counts. We report the presence of PER2 expression in 20 forebrain
      areas important for a wide range of motivated and appetitive behaviors including
      the SCN, bed nucleus, and several regions of the amygdala, hippocampus, striatum,
      and cortex. Eighteen areas displayed significant PER2 rhythms, which peaked at
      different times of day. Our data demonstrate a previously uncharacterized
      regional distribution of rhythms of a clock protein expression in the brain that
      provides a sound basis for future studies of circadian clock function in animal
      models of disease. 

PMID- 24124557
TI  - Adipose tissue-derived mesenchymal stem cells increase skin allograft survival
      and inhibit Th-17 immune response.
AB  - Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive
      capabilities both in vitro and in vivo. Their use for therapy in the transplant
      field is attractive as they could render the use of immunosuppressive drugs
      unnecessary. The aim of this study was to investigate the effect of ADSC therapy
      on prolonging skin allograft survival. Animals that were treated with a single
      injection of donor allogeneic ADSC one day after transplantation showed an
      increase in donor skin graft survival by approximately one week. This improvement
      was associated with preserved histological morphology, an expansion of CD4(+)
      regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10
      expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naive
      CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In
      summary, infusion of ADSC one day post-transplantation dramatically increases
      skin allograft survival by inhibiting the Th-17 pathogenic immune response and
      enhancing the protective Treg immune response. Finally, these data suggest that
      ADSC therapy will open new opportunities for promoting drug-free allograft
      survival in clinical transplantation.

PMID- 24124558
TI  - New castanospermine glycoside analogues inhibit breast cancer cell proliferation
      and induce apoptosis without affecting normal cells.
AB  - sp2-Iminosugar-type castanospermine analogues have been shown to exhibit anti
      tumor activity. However, their effects on cell proliferation and apoptosis and
      the molecular mechanism at play are not fully understood. Here, we investigated
      the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2
      oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231
      breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO
      OCS inhibited breast cancer cell viability in a concentration- and time-dependent
      manner. This effect is specific to breast cancer cells as both molecules had no
      impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle
      arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells
      respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of
      CDK4 (cyclin-dependent kinase 4), cyclin D1 and cyclin E expression, pRb
      phosphorylation, and an overexpression of p21(Waf1/Cip1). In MDA-MB-231 cells, CO
      OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M
      in both cell lines and this blockade was accompanied by a decrease of CDK1, but
      not cyclin B1 expression. Furthermore, both drugs induced apoptosis as
      demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl
      2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify
      cell proliferation, cell cycle progression, cyclins, or CDKs expression. These
      results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both
      cell cycle arrest and apoptosis, suggesting that these castanospermine analogues
      may constitute potential anti-cancer agents against breast cancer.

PMID- 24124560
TI  - Expression, purification and low-resolution structure of human vitamin C
      transporter SVCT1 (SLC23A1).
AB  - Expression and purification of human membrane proteins for structural studies
      represent a great challenge. This is because micro- to milligram amounts of pure
      isolated protein are required. To this aim, we successfully expressed the human
      vitamin C transporter-1 (hSVCT1; SLC23A1) in Xenopus laevis oocytes and isolated
      highly pure protein in microgram amounts. Recombinant hSVCT1 was functional when
      expressed in oocytes and glycosylated. Structural analysis of purified hSVCT1 by
      transmission electron microscopy and single particle analysis unveiled its shape,
      dimensions and low-resolution structure as well as the existence of a major
      monomeric and minor dimeric population. Chemical crosslinking of isolated oocyte
      membranes containing expressed hSVCT1 indicated similar oligomeric states of
      hSVCT1 in lipid bilayers. This work reports the first purification and structural
      analysis of a human SVCT protein and opens the way for future functional and
      structural studies using purified hSVCT1.

PMID- 24124559
TI  - A novel large in-frame deletion within the CACNA1F gene associates with a cone
      rod dystrophy 3-like phenotype.
AB  - Cone-rod dystrophies (CORDs) represent a heterogeneous group of monogenic
      diseases leading to early impairment of vision. The majority of CORD entities
      show autosomal modes of inheritance and X-linked traits are comparably rare. So
      far, three X-chromosomal entities were reported (CORDX1, -X2 and -X3). In this
      study, we analysed a large family of German origin with solely affected males
      over three generations showing a CORDX-like phenotype. Due to the heterogeneity
      of cone-rod dystrophies, we performed a combined linkage and X-exome sequencing
      approach and identified a novel large intragenic in-frame deletion encompassing
      exons 18 to 26 within the CACNA1F gene. CACNA1F is described causative for CORDX3
      in a single family originating from Finland and alterations in this gene have not
      yet been reported in other CORDX pedigrees. Our data independently confirm
      CACNA1F as the causative gene for CORDX3-like phenotypes and detailed clinical
      characterization of the family expands the knowledge about the phenotypic
      spectrum of deleterious CACNA1F alterations. 

PMID- 24124561
TI  - Predictors of diastolic-to-wedge gradient in patients evaluated for pulmonary
      hypertension.
AB  - BACKGROUND: Differentiation of pulmonary arterial hypertension (PAH) and
      pulmonary venous hypertension (PVH) often requires right heart catheterization
      (RHC). We sought to determine whether a combination of clinical and
      echocardiographic variables could predict the pulmonary diastolic to wedge (PAd
      PWP) gradient and thus differentiate patients with PAH and PVH. METHODS: We
      prospectively enrolled 108 patients presenting for PH evaluation. We developed a
      multivariate model to predict PAd-PWP gradient and validated this model using
      bootstrapping technique. RESULTS: PAH patients had worse hemodynamics and were
      more likely to have evidence of right ventricular dilation and dysfunction
      whereas patients with PVH were older and more likely to have features of the
      metabolic syndrome. PAd-PWP gradient of >= 6 mm Hg accurately discriminated
      patients with PAH compared to PVH. Our model including clinical and
      echocardiographic variables was highly accurate for the prediction of PAd-PWP
      gradient with a slope 0.89 (slope of 1 represents perfect prediction).
      CONCLUSIONS: In this prospective study of patients referred for PH evaluation, a
      model of readily available clinical parameters and simple echocardiographic
      measurements accurately predicted the PAd-PWP gradient, allowing discrimination
      of patients with PAH and PVH. This model requires validation in a larger cohort,
      but may afford clinicians more parsimony with referral for invasive testing in
      the evaluation of PH.

PMID- 24124562
TI  - Impairment of autophagic flux promotes glucose reperfusion-induced neuro2A cell
      death after glucose deprivation.
AB  - Hypoglycemia-induced brain injury is a common and serious complication of
      intensive insulin therapy experienced by Type 1 diabetic patients. We previously
      reported that hypoglycemic neuronal death is triggered by glucose reperfusion
      after hypoglycemia rather than as a simple result of glucose deprivation.
      However, the precise mechanism of neuronal death initiated by glucose reperfusion
      is still unclear. Autophagy is a self-degradation process that acts through a
      lysosome-mediated trafficking pathway to degrade and recycle intracellular
      components, thereby regulating metabolism and energy production. Recent studies
      suggest that autophagic and lysosomal dysfunction leads to abnormal protein
      degradation and deposition that may contribute to neuronal death. Here, we
      focused on the relationship between autophagy and lysosomal dysfunction in
      hypoglycemia-induced neuronal death. In neuronal cells, glucose reperfusion after
      glucose deprivation resulted in inhibition of autophagy, which may promote cell
      death. This cell death was accompanied with activation of caspase3 and the
      lysosomal proteases cathepsin B and D, which indicated impairment of autophagic
      flux. Taken together, these results suggest that interplay of autophagy, caspase3
      activation and lysosomal proteases serve as a basis for neuronal death after
      hypoglycemia. Thus, we provide the molecular mechanism of neuronal death by
      glucose reperfusion and suggest some clues for therapeutic strategies to prevent
      hypoglycemia-induced neuronal death.

PMID- 24124563
TI  - Cytoprotective effect of recombinant human erythropoietin produced in transgenic
      tobacco plants.
AB  - Asialo-erythropoietin, a desialylated form of human erythropoietin (EPO) lacking
      hematopoietic activity, is receiving increased attention because of its broader
      protective effects in preclinical models of tissue injury. However, attempts to
      translate its protective effects into clinical practice is hampered by
      unavailability of suitable expression system and its costly and limit production
      from expensive mammalian cell-made EPO (rhuEPO(M)) by enzymatic desialylation. In
      the current study, we took advantage of a plant-based expression system lacking
      sialylating capacity but possessing an ability to synthesize complex N-glycans to
      produce cytoprotective recombinant human asialo-rhuEPO. Transgenic tobacco plants
      expressing asialo-rhuEPO were generated by stably co-expressing human EPO and
      beta1,4-galactosyltransferase (GalT) genes under the control of double CaMV 35S
      and glyceraldehyde-3-phosphate gene (GapC) promoters, respectively. Plant
      produced asialo-rhuEPO (asialo-rhuEPO(P)) was purified by immunoaffinity
      chromatography. Detailed N-glycan analysis using NSI-FTMS and MS/MS revealed that
      asialo-rhuEPO(P) bears paucimannosidic, high mannose-type and complex N-glycans.
      In vitro cytoprotection assays showed that the asialo-rhuEPO(P) (20 U/ml)
      provides 2-fold better cytoprotection (44%) to neuronal-like mouse neuroblastoma
      cells from staurosporine-induced cell death than rhuEPO(M) (21%). The
      cytoprotective effect of the asialo-rhuEPO(P) was found to be mediated by
      receptor-initiated phosphorylation of Janus kinase 2 (JAK2) and suppression of
      caspase 3 activation. Altogether, these findings demonstrate that plants are a
      suitable host for producing cytoprotective rhuEPO derivative. In addition, the
      general advantages of plant-based expression system can be exploited to address
      the cost and scalability issues related to its production.

PMID- 24124564
TI  - Postnatal temporal, spatial and modality tuning of nociceptive cutaneous flexion
      reflexes in human infants.
AB  - Cutaneous flexion reflexes are amongst the first behavioural responses to develop
      and are essential for the protection and survival of the newborn organism.
      Despite this, there has been no detailed, quantitative study of their maturation
      in human neonates. Here we use surface electromyographic (EMG) recording of
      biceps femoris activity in preterm (<37 weeks gestation, GA) and term (>= 37
      weeks GA) human infants, less than 14 days old, in response to tactile, punctate
      and clinically required skin-breaking lance stimulation of the heel. We show that
      all infants display a robust and long duration flexion reflex (>4 seconds) to a
      single noxious skin lance which decreases significantly with gestational age.
      This reflex is not restricted to the stimulated limb: heel lance evokes equal
      ipsilateral and contralateral reflexes in preterm and term infants. We further
      show that infant flexion withdrawal reflexes are not always nociceptive specific:
      in 29% of preterm infants, tactile stimulation evokes EMG activity that is
      indistinguishable from noxious stimulation. In 40% of term infants, tactile
      responses are also present but significantly smaller than nociceptive reflexes.
      Infant flexion reflexes are also evoked by application of calibrated punctate von
      Frey hairs (vFh), 0.8-17.2 g, to the heel. Von Frey hair thresholds increase
      significantly with gestational age and the magnitude of vFh evoked reflexes are
      significantly greater in preterm than term infants. Furthermore flexion reflexes
      in both groups are sensitized by repeated vFh stimulation. Thus human infant
      flexion reflexes differ in temporal, modality and spatial characteristics from
      those in adults. Reflex magnitude and tactile sensitivity decreases and
      nociceptive specificity and spatial organisation increases with gestational age.
      Strong, relatively non-specific, reflex sensitivity in early life may be
      important for driving postnatal activity dependent maturation of targeted spinal
      cord sensory circuits.

PMID- 24124565
TI  - DNA damage responses and oxidative stress in dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is an inherited multisystem disorder of premature
      aging, cancer predisposition, and bone marrow failure caused by selective
      exhaustion of highly proliferative cell pools. DC patients also have a poor
      tolerance to chemo/radiotherapy and bone marrow transplantation. Although
      critically shortened telomeres and defective telomere maintenance contribute to
      DC pathology, other mechanisms likely exist. We investigate the link between
      telomere dysfunction and oxidative and DNA damage response pathways and assess
      the effects of antioxidants. In vitro studies employed T lymphocytes from DC
      subjects with a hTERC mutation and age-matched controls. Cells were treated with
      cytotoxic agents, including Paclitaxel, Etoposide, or ionizing radiation.
      Apoptosis and reactive oxygen species (ROS) were assessed by flow cytometry, and
      Western blotting was used to measure expression of DNA damage response (DDR)
      proteins, including total p53, p53S15, and p21(WAF). N-acetyl-cysteine (NAC), an
      antioxidant, was used to modulate cell growth and ROS. In stimulated culture, DC
      lymphocytes displayed a stressed phenotype, characterized by elevated levels of
      ROS, DDR and apoptotic markers as well as a proliferative defect that was more
      pronounced after exposure to cytotoxic agents. NAC partially ameliorated the
      growth disadvantage of DC cells and decreased radiation-induced apoptosis and
      oxidative stress. These findings suggest that oxidative stress may play a role in
      the pathogenesis of DC and that pharmacologic intervention to correct this pro
      oxidant imbalance may prove useful in the clinical setting, potentially
      alleviating untoward toxicities associated with current cytotoxic treatments. 

PMID- 24124566
TI  - Is vitamin D binding protein a novel predictor of labour?
AB  - Vitamin D binding protein (VDBP) has previously been identified in the amniotic
      fluid and cervicovaginal fluid (CVF) of pregnant women. The biological functions
      of VDBP include acting as a carrier protein for vitamin D metabolites, the
      clearance of actin that is released during tissue injury and the augmentation of
      the pro-inflammatory response. This longitudinal observational study was
      conducted on 221 healthy pregnant women who spontaneously laboured and delivered
      either at term or preterm. Serial CVF samples were collected and VDBP was
      measured by ELISA. Binary logistic regression analysis was performed to assess
      the utility of VDBP as a predictor of labour. VDBP in the CVF did not change
      between 20 and 35 weeks' gestation. VDBP measured in-labour was significantly
      increased 4.2 to 7.4-fold compared to 4-7, 8-14 and 15-28 days before labour
      (P<0.05). VDBP concentration was 4.3-fold significantly higher at 0-3 days
      compared to 15-28 days pre-labour (P<0.05). The efficacy of VDBP to predict
      spontaneous labour onset within 3 days provided a positive and negative
      predictive value of 82.8% and 95.3% respectively (area under receiver operator
      characteristic curve  = 0.974). This longitudinal study of pregnant women
      suggests that VDBP in the CVF may be a useful predictor of labour.

PMID- 24124567
TI  - Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by
      counteracting oxidative stress at multiple levels.
AB  - Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found
      mostly in young adults in the western world. Oxidative stress induced neuronal
      apoptosis plays an important role in the pathogenesis of MS. In current study,
      astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus
      membranceus, given at 20 mg/kg daily attenuated the severity of experimental
      autoimmune encephalomyelitis (EAE) in mice significantly. Further studies
      disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory
      cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of
      iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the
      leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was
      reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration
      into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS
      level and phosphorylation of tau in response to hydrogen peroxide challenge by
      modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in
      vivo and in vitro. iNOS up-regulation induced by IFNgamma stimulation was
      abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the
      severity of EAE progression possibly by counterbalancing oxidative stress and its
      effects via reduction of cellular ROS level, enhancement of antioxidant defense
      system, increase of anti-apoptotic and anti-inflammatory pathways, as well as
      modulation of T-cell differentiation and infiltration into CNS. The study
      suggested ASI may be effective for clinical therapy/prevention of MS. 

PMID- 24124568
TI  - Response of the abundance of key soil microbial nitrogen-cycling genes to multi
      factorial global changes.
AB  - Multiple co-occurring environmental changes are affecting soil nitrogen cycling
      processes, which are mainly mediated by microbes. While it is likely that various
      nitrogen-cycling functional groups will respond differently to such environmental
      changes, very little is known about their relative responsiveness. Here we
      conducted four long-term experiments in a steppe ecosystem by removing plant
      functional groups, mowing, adding nitrogen, adding phosphorus, watering, warming,
      and manipulating some of their combinations. We quantified the abundance of seven
      nitrogen-cycling genes, including those for fixation (nifH), mineralization
      (chiA), nitrification (amoA of ammonia-oxidizing bacteria (AOB) or archaea
      (AOA)), and denitrification (nirS, nirK and nosZ). First, for each gene, we
      compared its sensitivities to different environmental changes and found that the
      abundances of various genes were sensitive to distinct and different factors.
      Overall, the abundances of nearly all genes were sensitive to nitrogen
      enrichment. In addition, the abundances of the chiA and nosZ genes were sensitive
      to plant functional group removal, the AOB-amoA gene abundance to phosphorus
      enrichment when nitrogen was added simultaneously, and the nirS and nirK gene
      abundances responded to watering. Second, for each single- or multi-factorial
      environmental change, we compared the sensitivities of the abundances of
      different genes and found that different environmental changes primarily affected
      different gene abundances. Overall, AOB-amoA gene abundance was most responsive,
      followed by the two denitrifying genes nosZ and nirS, while the other genes were
      less sensitive. These results provide, for the first time, systematic insights
      into how the abundance of each type of nitrogen-cycling gene and the equilibrium
      state of all these nitrogen-cycling gene abundances would shift under each single
      or multi-factorial global change. 

PMID- 24124569
TI  - Kinetics of miR-122 expression in the liver during acute HCV infection.
AB  - The relationships among micro RNA-122 (miR-122) expression in the liver,
      hepatitis C virus (HCV) replication and hepatic damage were analyzed in three
      chimpanzees observed for 180 days after inoculation with HCV genotype 1a. Levels
      of miR-122 in the liver and serum were measured by real-time RT PCR in serial
      liver biopsies and serum samples. Hepatic miR-122 levels were normalized
      separately for each of three chimpanzees with small RNAs and microRNAs that are
      endogenous to the liver and are stably expressed. Two- to 4-fold rise in hepatic
      miR-122 levels was observed at the onset of HCV infection (the first 4 weeks)
      when HCV titers in the liver and serum increased rapidly in all three chimpanzees
      in concordance with in vitro data indicating the miR-122 significance for HCV
      replication. Between 10 to 14 weeks after inoculation, when hepatic and serum HCV
      RNA titers exceeded 3 logs and alanine aminotransferase (ALT) activity was
      elevated, hepatic miR-122 levels were in decline. Cumulative data derived from
      all three chimpanzees from 180 days of observation documented an inverse
      (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum
      and positive correlation between level of serum miR-122 and HCV replication.
      Subsequent rise of miR-122 level during HCV clearance and ALT normalization
      suggested a tri-phasic occurrence of the relationship among hepatic miR-122
      expression, HCV replication and hepatic destruction, which was the most apparent
      in one chimpanzee but less evident in two other animals. In vivo kinetics of
      hepatic and serum miR-122, HCV replication and hepatic destruction reflects
      complexities of the virus-host interaction during the acute phase of HCV
      infection. 

PMID- 24124570
TI  - MEK inhibitor U0126 reverses protection of axons from Wallerian degeneration
      independently of MEK-ERK signaling.
AB  - Wallerian degeneration is delayed when sufficient levels of proteins with NMNAT
      activity are maintained within axons after injury. This has been proposed to form
      the basis of 'slow Wallerian degeneration' (Wld (S)), a neuroprotective phenotype
      conferred by an aberrant fusion protein, Wld(S). Proteasome inhibition also
      delays Wallerian degeneration, although much less robustly, with stabilization of
      NMNAT2 likely to play a key role in this mechanism. The pan-MEK inhibitor U0126
      has previously been shown to reverse the axon-protective effects of proteasome
      inhibition, suggesting that MEK-ERK signaling plays a role in delayed Wallerian
      degeneration, in addition to its established role in promoting neuronal survival.
      Here we show that whilst U0126 can also reverse Wld(S)-mediated axon protection,
      more specific inhibitors of MEK1/2 and MEK5, PD184352 and BIX02189, have no
      significant effect on the delay to Wallerian degeneration in either situation,
      whether used alone or in combination. This suggests that an off-target effect of
      U0126 is responsible for reversion of the axon protective effects of Wld(S)
      expression or proteasome inhibition, rather than inhibition of MEK1/2-ERK1/2 or
      MEK5-ERK5 signaling. Importantly, this off-target effect does not appear to
      result in alterations in the stabilities of either Wld(S) or NMNAT2.

PMID- 24124571
TI  - Targeting wild-type and mutationally activated FGFR4 in rhabdomyosarcoma with the
      inhibitor ponatinib (AP24534).
AB  - Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. Despite
      advances in modern therapy, patients with relapsed or metastatic disease have a
      very poor clinical prognosis. Fibroblast Growth Factor Receptor 4 (FGFR4) is a
      cell surface tyrosine kinase receptor that is involved in normal myogenesis and
      muscle regeneration, but not commonly expressed in differentiated muscle tissues.
      Amplification and mutational activation of FGFR4 has been reported in RMS and
      promotes tumor progression. Therefore, FGFR4 is a tractable therapeutic target
      for patients with RMS. In this study, we used a chimeric Ba/F3 TEL-FGFR4
      construct to test five tyrosine kinase inhibitors reported to specifically
      inhibit FGFRs in the nanomolar range. We found ponatinib (AP24534) to be the most
      potent FGFR4 inhibitor with an IC50 in the nanomolar range. Ponatinib inhibited
      the growth of RMS cells expressing wild-type or mutated FGFR4 through increased
      apoptosis. Phosphorylation of wild-type and mutated FGFR4 as well as its
      downstream target STAT3 was also suppressed by ponatinib. Finally, ponatinib
      treatment inhibited tumor growth in a RMS mouse model expressing mutated FGFR4.
      Therefore, our data suggests that ponatinib is a potentially effective
      therapeutic agent for RMS tumors that are driven by a dysregulated FGFR4
      signaling pathway.

PMID- 24124572
TI  - Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.
AB  - Taste perception plays an important role in regulating food preference, eating
      behavior and energy homeostasis. Taste perception is modulated by a variety of
      factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth
      hormone release, food intake, adiposity, and energy metabolism. Octanoylation of
      ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational
      modification which is essential for many biological activities of ghrelin.
      Ghrelin and GOAT are both widely expressed in many organs including the gustatory
      system. In the current study, overall metabolic profiles were assessed in wild
      type (WT), ghrelin knockout (ghrelin(-/-)), and GOAT knockout (GOAT(-/-)) mice.
      Ghrelin(-/-) mice exhibited decreased food intake, increased plasma triglycerides
      and increased ketone bodies compared to WT mice while demonstrating WT-like body
      weight, fat composition and glucose control. In contrast GOAT(-/-) mice exhibited
      reduced body weight, adiposity, resting glucose and insulin levels compared to WT
      mice. Brief access taste behavioral tests were performed to determine taste
      responsivity in WT, ghrelin(-/-) and GOAT(-/-) mice. Ghrelin and GOAT null mice
      possessed reduced lipid taste responsivity. Furthermore, we found that salty
      taste responsivity was attenuated in ghrelin(-/-) mice, yet potentiated in GOAT(
      /-) mice compared to WT mice. Expression of the potential lipid taste regulators
      Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice,
      while the salt-sensitive ENaC subunit was increased in GOAT(-/-) mice compared
      with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible
      for the altered lipid and salt taste perception in ghrelin(-/-) and GOAT(-/-)
      mice. The data presented in the current study potentially implicates ghrelin
      signaling activity in the modulation of both lipid and salt taste modalities.

PMID- 24124573
TI  - Metabolism and fatty acid profile in fat and lean rainbow trout lines fed with
      vegetable oil: effect of carbohydrates.
AB  - The present study investigated the effect of dietary carbohydrates on metabolism,
      with special focus on fatty acid bioconversion and flesh lipid composition in two
      rainbow trout lines divergently selected for muscle lipid content and fed with
      vegetable oils. These lines were chosen based on previously demonstrated
      potential differences in LC-PUFA synthesis and carbohydrate utilization. Applying
      a factorial study design, juvenile trout from the lean (L) and the fat (F) line
      were fed vegetable oil based diets with or without gelatinised starch (17.1%) for
      12 weeks. Blood, liver, muscle, intestine and adipose tissue were sampled after
      the last meal. Feed intake and growth was higher in the L line than the F line,
      irrespective of the diet. Moderate postprandial hyperglycemia, strong induction
      of hepatic glucokinase and repressed glucose-6-phosphatase transcripts confirmed
      the metabolic response of both lines to carbohydrate intake. Further at the
      transcriptional level, dietary carbohydrate in the presence of n-3 LC-PUFA
      deficient vegetable oils enhanced intestinal chylomicron assembly, disturbed
      hepatic lipid metabolism and importantly elicited a higher response of key
      desaturase and elongase enzymes in the liver and intestine that endorsed our
      hypothesis. PPARgamma was identified as the factor mediating this dietary
      regulation of fatty acid bioconversion enzymes in the liver. However, these
      molecular changes were not sufficient to modify the fatty acid composition of
      muscle or liver. Concerning the genotype effect, there was no evidence of
      substantial genotypic difference in lipid metabolism, LC-PUFA synthesis and flesh
      fatty acid profile when fed with vegetable oils. The minor reduction in plasma
      glucose and triglyceride levels in the F line was linked to potentially higher
      glucose and lipid uptake in the muscle. Overall, these data emphasize the
      importance of dietary macro-nutrient interface in evolving fish nutrition
      strategies. 

PMID- 24124574
TI  - Patent human infections with the whipworm, Trichuris trichiura, are not
      associated with alterations in the faecal microbiota.
AB  - BACKGROUND: The soil-transmitted helminth (STH), Trichuris trichiura colonises
      the human large intestine where it may modify inflammatory responses, an effect
      possibly mediated through alterations in the intestinal microbiota. We
      hypothesised that patent T. trichiura infections would be associated with altered
      faecal microbiota and that anthelmintic treatment would induce a microbiota
      resembling more closely that observed in uninfected individuals. MATERIALS AND
      METHODS: School children in Ecuador were screened for STH infections and
      allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with
      T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those
      with T. trichiura infections only were given anthelmintic treatment. Bacterial
      community profiles in faecal samples were studied by 454 pyrosequencing of 16 S
      rRNA genes. RESULTS: Microbiota analyses of faeces were done for 97 children: 30
      were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and
      A. lumbricoides. Post-treatment samples were analyzed for 14 children initially
      infected with T. trichiura alone and for 21 uninfected children. Treatment
      resulted in 100% cure of STH infections. Comparisons of the microbiota at
      different taxonomic levels showed no statistically significant differences in
      composition between uninfected children and those with T. trichiura infections.
      We observed a decreased proportional abundance of a few bacterial genera from the
      Clostridia class of Firmicutes and a reduced bacterial diversity among children
      with mixed infections compared to the other two groups, indicating a possible
      specific effect of A. lumbricoides infection. Anthelmintic treatment of children
      with T. trichiura did not alter faecal microbiota composition. DISCUSSION: Our
      data indicate that patent human infections with T. trichiura may have no effect
      on faecal microbiota but that A. lumbricoides colonisation might be associated
      with a disturbed microbiota. Our results also catalogue the microbiota of rural
      Ecuadorians and indicate differences with individuals from more urban
      industrialised societies.

PMID- 24124575
TI  - Associations between vaginal pathogenic community and bacterial vaginosis in
      Chinese reproductive-age women.
AB  - BACKGROUND: Bacterial vaginosis (BV) is one of the most common urogenital
      infections among women of reproductive age that represents shifts in microbiota
      from Lactobacillus spp. to diverse anaerobes. The aim of our study was to evalute
      the diagnostic values of Gardnerella, Atopobium, Eggerthella, Megasphaera typeI,
      Leptotrichia/Sneathia and Prevotella, defined as a vaginal pathogenic community
      for BV and their associations with vaginal pH and Nugent scores. METHODS AND
      FINDINGS: We investigated the vaginal pathogenic bacteria and Lactobacillus spp.
      with species-specific real-time quantitative PCR (qPCR) in 50 BV-positive and 50
      BV-negative Chinese women of reproductive age. Relative to BV-negative subjects,
      a siginificant decline in Lactobacillus and an obvious increase in bacteria in
      the vaginal pathogenic community were observed in BV-postive subjects (P<0.05).
      With the exception of Megasphaera typeI, other vaginal pathogenic bacteria were
      highly predictable for BV with a better sensitivity and specificity. The vaginal
      pathogenic community was positively associated with vaginal pH and Nugent scores,
      while Lactobacillus spp., such as L. iners and L. crispatus was negatively
      associated with them (P<0.05). CONCLUSIONS: Our data implied that the prevalance
      of vaginal pathogenic bacteria as well as the depletion of Lactobacillus was
      highly accurate for BV diagnosis. Vaginal microbiota shifts, especially the
      overgrowth of the vaginal pathogenic community, showed well diagnostic values in
      predicting BV. Postive correlations between those vaginal pathogenic bacteria and
      vaginal pH, Nugent score indicated the vaginal pathogenic community rather than a
      single vaginal microorganism, was participated in the onset of BV directly.

PMID- 24124576
TI  - Shifted coupling of EEG driving frequencies and fMRI resting state networks in
      schizophrenia spectrum disorders.
AB  - INTRODUCTION: The cerebral resting state in schizophrenia is altered, as has been
      demonstrated separately by electroencephalography (EEG) and functional magnetic
      resonance imaging (fMRI) resting state networks (RSNs). Previous simultaneous
      EEG/fMRI findings in healthy controls suggest that a consistent spatiotemporal
      coupling between neural oscillations (EEG frequency correlates) and RSN activity
      is necessary to organize cognitive processes optimally. We hypothesized that this
      coupling is disorganized in schizophrenia and related psychotic disorders, in
      particular regarding higher cognitive RSNs such as the default-mode (DMN) and
      left-working-memory network (LWMN). METHODS: Resting state was investigated in
      eleven patients with a schizophrenia spectrum disorder (n = 11) and matched
      healthy controls (n = 11) using simultaneous EEG/fMRI. The temporal association
      of each RSN to topographic spectral changes in the EEG was assessed by creating
      Covariance Maps. Group differences within, and group similarities across
      frequencies were estimated for the Covariance Maps. RESULTS: The coupling of EEG
      frequency bands to the DMN and the LWMN respectively, displayed significant
      similarities that were shifted towards lower EEG frequencies in patients compared
      to healthy controls. CONCLUSIONS: By combining EEG and fMRI, each measuring
      different properties of the same pathophysiology, an aberrant relationship
      between EEG frequencies and altered RSNs was observed in patients. RSNs of
      patients were related to lower EEG frequencies, indicating functional alterations
      of the spatiotemporal coupling. SIGNIFICANCE: The finding of a deviant and
      shifted coupling between RSNs and related EEG frequencies in patients with a
      schizophrenia spectrum disorder is significant, as it might indicate how failures
      in the processing of internal and external stimuli, as commonly seen during this
      symptomatology (i.e. thought disorders, hallucinations), arise.

PMID- 24124577
TI  - Molecular dynamics simulations of double-stranded DNA in an explicit solvent
      model with the zero-dipole summation method.
AB  - Molecular dynamics (MD) simulations of a double-stranded DNA with explicit water
      and small ions were performed with the zero-dipole summation (ZD) method, which
      was recently developed as one of the non-Ewald methods. Double-stranded DNA is
      highly charged and polar, with phosphate groups in its backbone and their
      counterions, and thus precise treatment for the long-range electrostatic
      interactions is always required to maintain the stable and native double-stranded
      form. A simple truncation method deforms it profoundly. On the contrary, the ZD
      method, which considers the neutralities of charges and dipoles in a truncated
      subset, well reproduced the electrostatic energies of the DNA system calculated
      by the Ewald method. The MD simulations using the ZD method provided a stable DNA
      system, with similar structures and dynamic properties to those produced by the
      conventional Particle mesh Ewald method. 

PMID- 24124578
TI  - Association between tumor necrosis factor-alpha 308G/A gene polymorphism and
      silicosis susceptibility: a meta-analysis.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) 308 G/A gene polymorphism has
      been reported to be associated with susceptibility to silicosis. However, the
      relevant study results are still inconsistent. OBJECTIVE AND METHODS: A meta
      analysis was performed in order to drive a more precise estimation of the
      relationship between TNF-alpha-308 G/A gene polymorphism and susceptibility to
      silicosis. Electronic databases were searched and nine separate studies were
      included. The pooled odds ratios (ORs) and the corresponding 95% confidence
      internal (CI) were calculated by a fixed effect model. RESULTS: A total of 1267
      cases and 1214 controls were included. In the overall analysis, significantly
      increased silicosis risk was found (for GA+AA vs. GG OR=1.45, 95%CI: 1.20-1.760,
      P=1.58E4; for GA vs. GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs. G
      allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). In the subgroup analysis,
      significantly increased silicosis risk was also found among Asians (for GA+AA vs.
      GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs. GG: OR=1.71, 95%CI=1.33-2.20,
      P=3.44E5), for A allele vs. G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001).
      However, no significantly increased risk was found among non-Asians for all
      genetic models. CONCLUSIONS: TNF-alpha-308 G/A polymorphism might lead to an
      increased risk of silicosis susceptibility, especially for Asians. However,
      further studies with large sample sizes should be conducted to confirm the
      association.

PMID- 24124579
TI  - Screening E3 substrates using a live phage display library.
AB  - Ubiquitin ligases (E3s) determine specificity of ubiquitination by recognizing
      target substrates. However, most of their substrates are unknown. Most known
      substrates have been identified using distinct approaches in different
      laboratories. We developed a high-throughput strategy using a live phage display
      library as E3 substrates in in vitro screening. His-ubiquitinated phage, enriched
      with Ni-beads, could effectively infect E. coli for amplification. Sixteen
      natural potential substrates and many unnatural potential substrates of E3 MDM2
      were identified through 4 independent screenings. Some substrates were identified
      in different independent experiments. Additionally, 10 of 12 selected candidates
      were ubiquitinated by MDM2 in vitro, and 3 novel substrates, DDX42, TP53RK and
      RPL36a were confirmed ex vivo. The whole strategy is rather simple and efficient.
      Non-degradation substrates can be discovered. This strategy can be extended to
      any E3s as long as the E3 does not ubiquitinate the empty phage. 

PMID- 24124580
TI  - Inconsistencies in quality of life data collection in clinical trials: a
      potential source of bias? Interviews with research nurses and trialists.
AB  - BACKGROUND: Patient-reported outcomes (PROs), such as health-related quality of
      life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical
      trials, are valued by patients, and may inform important decisions in the
      clinical setting. It is of concern, therefore, that preliminary evidence, gained
      from group discussions at UK-wide Medical Research Council (MRC) quality of life
      training days, suggests there are inconsistent standards of HRQL data collection
      in trials and appropriate training and education is often lacking. Our objective
      was to investigate these reports, to determine if they represented isolated
      experiences, or were indicative of a potentially wider problem. METHODS AND
      FINDINGS: We undertook a qualitative study, conducting 26 semi-structured
      interviews with research nurses, data managers, trial coordinators and research
      facilitators involved in the collection and entry of HRQL data in clinical
      trials, across one primary care NHS trust, two secondary care NHS trusts and two
      clinical trials units in the UK. We used conventional content analysis to analyze
      and interpret our data. Our study participants reported (1) inconsistent
      standards in HRQL measurement, both between, and within, trials, which appeared
      to risk the introduction of bias; (2), difficulties in dealing with HRQL data
      that raised concern for the well-being of the trial participant, which in some
      instances led to the delivery of non-protocol driven co-interventions, (3), a
      frequent lack of HRQL protocol content and appropriate training and education of
      trial staff, and (4) that HRQL data collection could be associated with emotional
      and/or ethical burden. CONCLUSIONS: Our findings suggest there are
      inconsistencies in the standards of HRQL data collection in some trials resulting
      from a general lack of HRQL-specific protocol content, training and education.
      These inconsistencies could lead to biased HRQL trial results. Future research
      should aim to develop HRQL guidelines and training programmes aimed at supporting
      researchers to carry out high quality data collection.

PMID- 24124581
TI  - Biochemical characterization of novel retroviral integrase proteins.
AB  - Integrase is an essential retroviral enzyme, catalyzing the stable integration of
      reverse transcribed DNA into cellular DNA. Several aspects of the integration
      mechanism, including the length of host DNA sequence duplication flanking the
      integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences
      at the site of integration, are thought to cluster among the different retroviral
      genera. To date only the spumavirus prototype foamy virus integrase has provided
      diffractable crystals of integrase-DNA complexes, revealing unprecedented details
      on the molecular mechanisms of DNA integration. Here, we characterize five
      previously unstudied integrase proteins, including those derived from the
      alpharetrovirus lymphoproliferative disease virus (LPDV), betaretroviruses
      Jaagsiekte sheep retrovirus (JSRV), and mouse mammary tumor virus (MMTV),
      epsilonretrovirus walleye dermal sarcoma virus (WDSV), and gammaretrovirus
      reticuloendotheliosis virus strain A (Rev-A) to identify potential novel
      structural biology candidates. Integrase expressed in bacterial cells was
      analyzed for solubility, stability during purification, and, once purified, 3'
      processing and DNA strand transfer activities in vitro. We show that while we
      were unable to extract or purify accountable amounts of WDSV, JRSV, or LPDV
      integrase, purified MMTV and Rev-A integrase each preferentially support the
      concerted integration of two viral DNA ends into target DNA. The sequencing of
      concerted Rev-A integration products indicates high fidelity cleavage of target
      DNA strands separated by 5 bp during integration, which contrasts with the 4 bp
      duplication generated by a separate gammaretrovirus, the Moloney murine leukemia
      virus (MLV). By comparing Rev-A in vitro integration sites to those generated by
      MLV in cells, we concordantly conclude that the spacing of target DNA cleavage is
      more evolutionarily flexible than are the target DNA base contacts made by
      integrase during integration. Given their desirable concerted DNA integration
      profiles, Rev-A and MMTV integrase proteins have been earmarked for structural
      biology studies. 

PMID- 24124582
TI  - Personality factors and suicide risk in a representative sample of the German
      general population.
AB  - OBJECTIVE: Previous research has shown an association between certain personality
      characteristics and suicidality. Methodological differences including small
      sample sizes and missing adjustment for possible confounding factors could
      explain the varying results. The aim of this study was to assess the impact of
      the Big Five personality dimensions on suicidality in a representative population
      based sample of adults. METHOD: Interviews were conducted in a representative
      German population-based sample (n=2555) in 2011. Personality characteristics were
      assessed using the Big Five Inventory-10 (BFI-10) and suicide risk was assessed
      with the Suicidal Behaviors Questionnaire-Revised (SBQ-R). Multivariate logistic
      regression models were calculated adjusting for depression, anxiety, and various
      sociodemographic variables. RESULTS: Neuroticism and openness were significantly
      associated with suicide risk, while extraversion and conscientiousness were found
      to be protective. Significant sex differences were observed. For males,
      extraversion and conscientiousness were protective factors. Neuroticism and
      openness were found to be associated with suicide risk only in females. These
      associations remained significant after adjusting for covariates. CONCLUSION: The
      results highlight the role of personality dimensions as risk factors for suicide
      related behaviors. Different personality dimensions are significantly associated
      with suicide-related behaviors even when adjusting for other known risk factors
      of suicidality.

PMID- 24124583
TI  - Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and
      refractory to sevoflurane-induced protection.
AB  - Recent studies have demonstrated that volatile anesthetic postconditioning
      confers myocardial protection against ischemia-reperfusion (IR) injury through
      activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has
      been shown to be impaired in hypercholesterolemia. Therefore, we investigate
      whether anesthetic-induced cardiac protection was maintained in
      hypercholesterolemic rats. In the present study, normocholesteolemic or
      hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of
      reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s
      ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular
      developed pressure, left ventricular end-diastolic pressure and heart rate, were
      continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3beta
      were determined. We found that both sevoflurane and ischemic postconditioning
      significantly improved heart pump function, reduced infarct size and increased
      the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3beta in the
      healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic
      postconditioning improved left ventricular hemodynamics, reduced infarct size and
      increased the phosphorylated Akt, ERK1/2 and GSK3beta. In contrast, GSK inhibitor
      SB216763 conferred cardioprotection against IR injury in healthy and
      hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated
      sevoflurane-induced cardioprotection against IR injury by alteration of upstream
      signaling of GSK3beta and acute GSK inhibition may provide a novel therapeutic
      strategy to protect hypercholesterolemic hearts against IR injury.

PMID- 24124584
TI  - Impact of the phosphatidylinositide 3-kinase signaling pathway on the
      cardioprotection induced by intermittent hypoxia.
AB  - BACKGROUND: Exposure to intermittent hypoxia (IH) may enhance cardiac function
      and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the
      underlying mechanisms, we developed a cardioprotective IH model that was
      characterized at hemodynamic, biochemical and molecular levels. METHODS: Mice
      were exposed to 4 daily IH cycles (each composed of 2-min at 6-8% O2 followed by
      3-min reoxygenation for 5 times) for 14 days, with normoxic mice as controls.
      Mice were then anesthetized and subdivided in various subgroups for analysis of
      contractility (pressure-volume loop), morphology, biochemistry or resistance to
      I/R (30-min occlusion of the left anterior descending coronary artery (LAD)
      followed by reperfusion and measurement of the area at risk and infarct size). In
      some mice, the phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin was
      administered (24 ug/kg ip) 15 min before LAD. RESULTS: We found that IH did not
      induce myocardial hypertrophy; rather both contractility and cardiac function
      improved with greater number of capillaries per unit volume and greater
      expression of VEGF-R2, but not of VEGF. Besides increasing the phosphorylation of
      protein kinase B (Akt) and the endothelial isoform of NO synthase with respect to
      control, IH reduced the infarct size and post-LAD proteins carbonylation, index
      of oxidative damage. Administration of wortmannin reduced the level of Akt
      phosphorylation and worsened the infarct size. CONCLUSION: We conclude that the
      PI3K/Akt pathway is crucial for IH-induced cardioprotection and may represent a
      viable target to reduce myocardial I/R injury.

PMID- 24124585
TI  - Generation of stable lipid raft microdomains in the enterocyte brush border by
      selective endocytic removal of non-raft membrane.
AB  - The small intestinal brush border has an unusually high proportion of glycolipids
      which promote the formation of lipid raft microdomains, stabilized by various
      cross-linking lectins. This unique membrane organization acts to provide physical
      and chemical stability to the membrane that faces multiple deleterious agents
      present in the gut lumen, such as bile salts, digestive enzymes of the pancreas,
      and a plethora of pathogens. In the present work, we studied the constitutive
      endocytosis from the brush border of cultured jejunal explants of the pig, and
      the results indicate that this process functions to enrich the contents of lipid
      raft components in the brush border. The lipophilic fluorescent marker FM, taken
      up into early endosomes in the terminal web region (TWEEs), was absent from
      detergent resistant membranes (DRMs), implying an association with non-raft
      membrane. Furthermore, neither major lipid raft-associated brush border enzymes
      nor glycolipids were detected by immunofluorescence microscopy in subapical
      punctae resembling TWEEs. Finally, two model raft lipids, BODIPY-lactosylceramide
      and BODIPY-GM1, were not endocytosed except when cholera toxin subunit B (CTB)
      was present. In conclusion, we propose that constitutive, selective endocytic
      removal of non-raft membrane acts as a sorting mechanism to enrich the brush
      border contents of lipid raft components, such as glycolipids and the major
      digestive enzymes. This sorting may be energetically driven by changes in
      membrane curvature when molecules move from a microvillar surface to an endocytic
      invagination.

PMID- 24124586
TI  - Behavioral and physiological changes during benthic-pelagic transition in the
      harmful alga, Heterosigma akashiwo: potential for rapid bloom formation.
AB  - Many species of harmful algae transition between a motile, vegetative stage in
      the water column and a non-motile, resting stage in the sediments. Physiological
      and behavioral traits expressed during benthic-pelagic transition potentially
      regulate the timing, location and persistence of blooms. The roles of key
      physiological and behavioral traits involved in resting cell emergence and bloom
      formation were examined in two geographically distinct strains of the harmful
      alga, Heterosigma akashiwo. Physiological measures of cell viability, division
      and population growth, and cell fatty acid content were made using flow cytometry
      and gas chromatography - mass spectrometry techniques as cells transitioned
      between the benthic resting stage and the vegetative pelagic stage. Video-based
      tracking was used to quantify cell-level swimming behaviors. Data show increased
      temperature and light triggered rapid emergence from the resting stage and
      initiated cell swimming. Algal strains varied in important physiological and
      behavioral traits, including survivorship during life-stage transitions,
      population growth rates and swimming velocities. Collectively, these traits
      function as "population growth strategies" that can influence bloom formation.
      Many resting cells regained the up-swimming capacity necessary to cross an
      environmentally relevant halocline and the ability to aggregate in near-surface
      waters within hours after vegetative growth supporting conditions were restored.
      Using a heuristic model, we illustrate how strain-specific population growth
      strategies can govern the timescales over which H. akashiwo blooms form. Our
      findings highlight the need for identification and quantification of strain
      specific physiological and behavioral traits to improve mechanistic understanding
      of bloom formation and successful bloom prediction.

PMID- 24124587
TI  - Identification of virulence properties in Salmonella Typhimurium DT104 using
      Caenorhabditis elegans.
AB  - Salmonella enterica serover Typhimurium definitive phage type DT104, resistant to
      multiple antibiotics, is one of the most widespread Salmonella species in human
      infection worldwide. Although several cohort studies indicate that DT104 carrying
      the multidrug resistance (MDR) locus on salmonella genomic island 1 is a possible
      hyper-virulent strain compared to DT104 strains without MDR, or other Salmonella
      enterica serotypes, existing experimental evidence regarding virulence properties
      associated with the MDR region is controversial. To address this question, we
      constructed an isogenic MDR deletion (?MDR) mutant strain of DT104, SNS12, by
      allelic exchange and used Caenorhabditis elegans as a host model to assess
      differences in virulence between these two strains. SNS12 exhibited decreased
      virulence in C. elegans, and we observed increased colonization and proliferation
      of the intestine of C. elegans by DT104. The immune response against MDR-carrying
      DT104 appears to function through a non-canonical Unfolded Protein Response (UPR)
      pathway, namely prion-like-(QN-rich)-domain-bearing protein pathway (PQN), in a
      ced-1 dependent manner in C. elegans. Further, we also demonstrate that genes of
      the PQN pathway and antimicrobial peptide gene abf-2, are expressed at higher
      transcriptional levels in worms immediately following exposure to DT104, in
      comparison with worms exposed to SNS12. Altogether, our results suggest that the
      MDR region of Salmonella Typhimurium DT104 has a direct role in virulence against
      Caenorhabditis elegans.

PMID- 24124588
TI  - The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with
      sepsis and after cardiopulmonary bypass.
AB  - BACKGROUND AND OBJECTIVES: Nociceptin/Orphanin FQ (N/OFQ) is a non-classical
      endogenous opioid peptide that modulates immune function in vitro. Its importance
      in inflammation and human sepsis is unknown. The objectives of this study were to
      determine the relationship between N/OFQ, transcripts for its precursor (pre-pro
      N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in
      patients undergoing cardiopulmonary bypass and with sepsis. METHODS: A
      prospective observational cohort study of 82 patients admitted to Intensive Care
      (ICU) with sepsis and 40 patients undergoing cardiac surgery under
      cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy
      volunteers, matched by age and sex to the patients with sepsis were also studied.
      Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor
      mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using
      ELISA and cytokines (TNF- alpha, IL-8, IL-10) measured using radioimmunoassay.
      Data from patients undergoing cardiac surgery were recorded before, 3 and 24
      hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on
      Days 1 and 2 of ICU admission, and after clinical recovery. MAIN RESULTS: Plasma
      N/OFQ concentrations increased (p<0.0001) on Days 1 and 2 of ICU admission with
      sepsis compared to matched recovery samples. Polymorph ppNOC (p= 0.019) and NOP
      mRNA (p<0.0001) decreased compared to healthy volunteers. TNF-alpha, IL-8 and IL
      10 concentrations increased on Day 1 compared to matched recovery samples and
      volunteers (p<0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058],
      decreased ppNOC [p<0.0001], increased IL-8 and IL-10 concentrations [both
      p<0.0001]) occurred after cardiac surgery but these were comparatively lower and
      of shorter duration. CONCLUSIONS: The N/OFQ system is modulated in ICU patients
      with sepsis with similar but reduced changes after cardiac surgery under
      cardiopulmonary bypass. Further studies are required to clarify the role of the
      N/OFQ system in inflammation and sepsis, and the mechanisms involved.

PMID- 24124589
TI  - Evolutionary origin of the mitochondrial cholesterol transport machinery reveals
      a universal mechanism of steroid hormone biosynthesis in animals.
AB  - Steroidogenesis begins with the transport of cholesterol from intracellular
      stores into mitochondria via a series of protein-protein interactions involving
      cytosolic and mitochondrial proteins located at both the outer and inner
      mitochondrial membranes. In adrenal glands and gonads, this process is
      accelerated by hormones, leading to the production of high levels of steroids
      that control tissue development and function. A hormone-induced multiprotein
      complex, the transduceosome, was recently identified, and is composed of
      cytosolic and outer mitochondrial membrane proteins that control the rate of
      cholesterol entry into the outer mitochondrial membrane. More recent studies
      unveiled the steroidogenic metabolon, a bioactive, multimeric protein complex
      that spans the outer-inner mitochondrial membranes and is responsible for hormone
      induced import, segregation, targeting, and metabolism of cholesterol by
      cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1) in the inner
      mitochondrial membrane. The availability of genome information allowed us to
      systematically explore the evolutionary origin of the proteins involved in the
      mitochondrial cholesterol transport machinery (transduceosome, steroidogenic
      metabolon, and signaling proteins), trace the original archetype, and predict
      their biological functions by molecular phylogenetic and functional divergence
      analyses, protein homology modeling and molecular docking. Although most members
      of these complexes have a history of gene duplication and functional divergence
      during evolution, phylogenomic analysis revealed that all vertebrates have the
      same functional complex members, suggesting a common mechanism in the first step
      of steroidogenesis. An archetype of the complex was found in invertebrates. The
      data presented herein suggest that the cholesterol transport machinery is
      responsible for steroidogenesis among all vertebrates and is evolutionarily
      conserved throughout the entire animal kingdom. 

PMID- 24124590
TI  - Residues in human arsenic (+3 oxidation state) methyltransferase forming
      potential hydrogen bond network around S-adenosylmethionine.
AB  - Residues Tyr59, Gly78, Ser79, Met103, Gln107, Ile136 and Glu137 in human arsenic
      (+3 oxidation state) methyltransferase (hAS3MT) were deduced to form a potential
      hydrogen bond network around S-adenosylmethionine (SAM) from the sequence
      alignment between Cyanidioschyzon merolae arsenite S-adenosylmethyltransferase
      (CmArsM) and hAS3MT. Herein, seven mutants Y59A, G78A, S79A, M103A, Q107A, I136A
      and E137A were obtained. Their catalytic activities and conformations were
      characterized and models were built. Y59A and G78A were completely inactive. Only
      7.0%, 10.6% and 13.8% inorganic arsenic (iAs) was transformed to monomethylated
      arsenicals (MMA) when M103A, Q107A and I136A were used as the enzyme. The Vmax
      (the maximal velocity of the reaction) values of M103A, Q107A, I136A and E137A
      were decreased to 8%, 22%, 15% and 50% of that of WT-hAS3MT, respectively. The
      KM(SAM) (the Michaelis constant for SAM) values of mutants M103A, I136A and E137A
      were 15.7, 8.9 and 5.1 fold higher than that of WT-hAS3MT, respectively,
      indicating that their affinities for SAM were weakened. The altered
      microenvironment of SAM and the reduced capacity of binding arsenic deduced from
      KM(As) (the Michaelis constant for iAs) value probably synergetically reduced the
      catalytic activity of Q107A. The catalytic activity of S79A was higher than that
      of WT despite of the higher KM(SAM) , suggesting that Ser79 did not impact the
      catalytic activity of hAS3MT. In short, residues Tyr59 and Gly78 significantly
      influenced the catalytic activity of hAS3MT as well as Met103, Ile136 and Glu137
      because they were closely associated with SAM-binding, while residue Gln107 did
      not affect SAM-binding regardless of affecting the catalytic activity of hAS3MT.
      Modeling and our experimental results suggest that the adenine ring of SAM is
      sandwiched between Ile136 and Met103, the amide group of SAM is hydrogen bonded
      to Gly78 in hAS3MT and SAM is bonded to Tyr59 with van der Waals, cation-pi and
      hydrogen bonding contacts.

PMID- 24124591
TI  - Effects of age, hemoglobin type and parasite strain on IgG recognition of
      Plasmodium falciparum-infected erythrocytes in Malian children.
AB  - BACKGROUND: Naturally-acquired antibody responses to antigens on the surface of
      Plasmodium falciparum-infected red blood cells (iRBCs) have been implicated in
      antimalarial immunity. To profile the development of this immunity, we have been
      studying a cohort of Malian children living in an area with intense seasonal
      malaria transmission. METHODOLOGY/PRINCIPAL FINDINGS: We collected plasma from a
      sub-cohort of 176 Malian children aged 3-11 years, before (May) and after
      (December) the 2009 transmission season. To measure the effect of hemoglobin (Hb)
      type on antibody responses, we enrolled age-matched HbAA, HbAS and HbAC children.
      To quantify antibody recognition of iRBCs, we designed a high-throughput flow
      cytometry assay to rapidly test numerous plasma samples against multiple parasite
      strains. We evaluated antibody reactivity of each plasma sample to 3 laboratory
      adapted parasite lines (FCR3, D10, PC26) and 4 short-term-cultured parasite
      isolates (2 Malian and 2 Cambodian). 97% of children recognized >=1 parasite
      strain and the proportion of IgG responders increased significantly during the
      transmission season for most parasite strains. Both strain-specific and strain
      transcending IgG responses were detected, and varied by age, Hb type and parasite
      strain. In addition, the breadth of IgG responses to parasite strains increased
      with age in HbAA, but not in HbAS or HbAC, children. CONCLUSIONS/SIGNIFICANCE:
      Our assay detects both strain-specific and strain-transcending IgG responses to
      iRBCs. The magnitude and breadth of these responses varied not only by age, but
      also by Hb type and parasite strain used. These findings indicate that studies of
      acquired humoral immunity should account for Hb type and test large numbers of
      diverse parasite strains.

PMID- 24124592
TI  - Leucine and HMB differentially modulate proteasome system in skeletal muscle
      under different sarcopenic conditions.
AB  - In the present study we have compared the effects of leucine supplementation and
      its metabolite beta-hydroxy-beta-methyl butyrate (HMB) on the ubiquitin
      proteasome system and the PI3K/Akt pathway during two distinct atrophic
      conditions, hindlimb immobilization and dexamethasone treatment. Leucine
      supplementation was able to minimize the reduction in rat soleus mass driven by
      immobilization. On the other hand, leucine supplementation was unable to provide
      protection against soleus mass loss in dexamethasone treated rats. Interestingly,
      HMB supplementation was unable to provide protection against mass loss in all
      treatments. While solely fiber type I cross sectional area (CSA) was protected in
      immobilized soleus of leucine-supplemented rats, none of the fiber types were
      protected by leucine supplementation in rats under dexamethasone treatment. In
      addition and in line with muscle mass results, HMB treatment did not attenuate
      CSA decrease in all fiber types against either immobilization or dexamethasone
      treatment. While leucine supplementation was able to minimize increased
      expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only
      able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB
      was unable to restrain the increase in those atrogenes in immobilized rats, but
      in dexamethasone treated rats, HMB minimized increased expression of
      Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased
      in immobilized and dexamethasone treated rats and only leucine was able to block
      this increase in immobilized rats but not in dexamethasone treated rats. Leucine
      supplementation maintained soleus tetanic peak force in immobilized rats at
      normal level. On the other hand, HMB treatment failed to maintain tetanic peak
      force regardless of treatment. The present data suggested that the anti-atrophic
      effects of leucine are not mediated by its metabolite HMB.

PMID- 24124593
TI  - Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial
      transition in human cancer.
AB  - Cell plasticity regulated by the balance between the mesenchymal to epithelial
      transition (MET) and the opposite program, EMT, is critical in the metastatic
      cascade. Several transcription factors (TFs) are known to regulate EMT, though
      the mechanisms of MET remain unclear. We demonstrate a novel function of two TFs,
      OVOL1 and OVOL2, as critical inducers of MET in human cancers. Our findings
      indicate that the OVOL-TFs control MET through a regulatory feedback loop with
      EMT-inducing TF ZEB1, and the regulation of mRNA splicing by inducing Epithelial
      Splicing Regulatory Protein 1 (ESRP1). Using mouse prostate tumor models we show
      that expression of OVOL-TFs in mesenchymal prostate cancer cells attenuates their
      metastatic potential. The role of OVOL-TFs as inducers of MET is further
      supported by expression analyses in 917 cancer cell lines, suggesting their role
      as crucial regulators of epithelial-mesenchymal cell plasticity in cancer.

PMID- 24124594
TI  - Sonic hedgehog regulates osteoblast function by focal adhesion kinase signaling
      in the process of fracture healing.
AB  - Several biological studies have indicated that hedgehog signaling plays an
      important role in osteoblast proliferation and differentiation, and sonic
      hedgehog (SHH) expression is positively correlated with phosphorylated focal
      adhesion kinase (FAK) Tyr(397). However, the relationship between them and their
      role in the process of normal fracture repair has not been clarified yet.
      Immunohistochemical analysis revealed that SHH and pFAK Tyr(397) were expressed
      in bone marrow cells and that pFAK Tyr(397) was also detected in ALP-positive
      osteoblasts near the TRAP-positive osteoclasts in the fracture site in the ribs
      of mice on day 5 after fracture. SHH and pFAK Tyr(397) were detectable in
      osteoblasts near the hypertrophic chondrocytes on day 14. In vitro analysis
      showed that SHH up-regulated the expression of FAK mRNA and pFAK Tyr(397) time
      dependently in osteoblastic MC3T3-E1 cells. Functional analysis revealed that 5
      lentivirus encoding short hairpin FAK RNAs (shFAK)-infected MC3T3-E1 cell groups
      displayed a round morphology and decreased proliferation, adhesion, migration,
      and differentiation. SHH stimulated the proliferation and differentiation of
      MC3T3-E1 cells, but had no effect on the shFAK-infected cells. SHH also
      stimulated osteoclast formation in a co-culture system containing MC3T3-E1 and
      murine CD11b(+) bone marrow cells, but did not affect the shFAK-infected MC3T3-E1
      co-culture group. These data suggest that SHH signaling was activated in
      osteoblasts at the dynamic remodeling site of a bone fracture and regulated their
      proliferation and differentiation, as well as osteoclast formation, via FAK
      signaling. 

PMID- 24124595
TI  - CXCL9 associated with sustained virological response in chronic hepatitis B
      patients receiving peginterferon alfa-2a therapy: a pilot study.
AB  - BACKGROUND AND AIMS: There is lack of a practical biomarker to predict sustained
      virological response (SVR) in chronic hepatitis B (CHB) patients undergoing
      peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify
      immunological features associated with SVR. METHODS: Consecutive 74 CHB patients
      receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for
      HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads,
      hepatitis B surface antigen (HBsAg), CXCL9, IFN-gamma-inducible protein 10 (IP
      10), interferon-gamma (IFN-gamma) and transforming growth factor beta (TGF-beta)
      were measured at baseline and week 12. SVR was defined as HBeAg seroconversion
      combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load
      <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of
      treatment. RESULTS: Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in
      HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg,
      IP-10 and IFN-gamma levels at week 12. In multivariate analysis, pre-treatment
      CXCL9 >80 pg/mL, HBV DNA <2.5 x 10(7) IU/mL and on-treatment HBV viral load,
      HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in
      predicting SVR was good in patients with HBV DNA <2.5 x 10(7) IU/mL, particularly
      in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%). CONCLUSIONS:
      Pre-treatment CXCL9 level has the potential to select CHB patients who can
      respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.

PMID- 24124596
TI  - Involvement of the Wnt/beta-catenin signaling pathway in the cellular and
      molecular mechanisms of fibrosis in endometriosis.
AB  - BACKGROUND: During the development and progression of endometriotic lesions,
      excess fibrosis may lead to scarring, chronic pain, and altered tissue function.
      However, the cellular and molecular mechanisms of fibrosis in endometriosis
      remain to be clarified. OBJECTIVES: The objective of the present study was to
      investigate whether the Wnt/beta-catenin signaling pathway was involved in
      regulating the cellular and molecular mechanisms of fibrosis in endometriosis in
      vitro and to evaluate whether fibrosis could be prevented by targeting the
      Wnt/beta-catenin pathway in a xenograft model of endometriosis in immunodeficient
      nude mice. METHODS: Seventy patients (40 with and 30 without endometriosis) with
      normal menstrual cycles were recruited. In vitro effects of small-molecule
      antagonists of the Tcf/beta-catenin complex (PKF 115-584 and CGP049090) on
      fibrotic markers (alpha smooth muscle actin, type I collagen, connective tissue
      growth factor, fibronectin) and collagen gel contraction were evaluated in
      endometrial and endometriotic stromal cells from patients with endometriosis. In
      vitro effects of activation of the Wnt/beta-catenin signaling pathway by
      treatment with recombinant Wnt3a on profibrotic responses were evaluated in
      endometrial stromal cells of patients without endometriosis. The effects of
      CGP049090 treatment on the fibrosis of endometriotic implants were evaluated in a
      xenograft model of endometriosis in immunodeficient nude mice. RESULTS: Treatment
      with PKF 115-584 and CGP049090 significantly decreased the expression of alpha
      smooth muscle actin, type I collagen, connective tissue growth factor and
      fibronectin mRNAs in both endometriotic and endometrial stromal cells with or
      without transforming growth factor-beta1 stimulation. Both endometriotic and
      endometrial stromal cell-mediated contraction of collagen gels was significantly
      decreased by treatment with PKF 115-584 and CGP049090 as compared to that of
      untreated cells. The animal experiments showed that CGP049090 prevented the
      progression of fibrosis and reversed established fibrosis in endometriosis.
      CONCLUSION: Aberrant activation of the Wnt/beta-catenin pathway may be involved
      in mediating fibrogenesis in endometriosis.

PMID- 24124597
TI  - Temporal characteristics of gustatory responses in rat parabrachial neurons vary
      by stimulus and chemosensitive neuron type.
AB  - It has been demonstrated that temporal features of spike trains can increase the
      amount of information available for gustatory processing. However, the nature of
      these temporal characteristics and their relationship to different taste
      qualities and neuron types are not well-defined. The present study analyzed the
      time course of taste responses from parabrachial (PBN) neurons elicited by
      multiple applications of "sweet" (sucrose), "salty" (NaCl), "sour" (citric acid),
      and "bitter" (quinine and cycloheximide) stimuli in an acute preparation. Time
      course varied significantly by taste stimulus and best-stimulus classification.
      Across neurons, the ensemble code for the three electrolytes was similar
      initially but quinine diverged from NaCl and acid during the second 500 ms of
      stimulation and all four qualities became distinct just after 1s. This temporal
      evolution was reflected in significantly broader tuning during the initial
      response. Metric space analyses of quality discrimination by individual neurons
      showed that increases in information (H) afforded by temporal factors was usually
      explained by differences in rate envelope, which had a greater impact during the
      initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover,
      timing had a differential impact according to cell type, with between-quality
      discrimination in neurons activated maximally by NaCl or citric acid most
      affected. Timing was also found to dramatically improve within-quality
      discrimination (80% increase in H) in neurons that responded optimally to bitter
      stimuli (B-best). Spikes from B-best neurons were also more likely to occur in
      bursts. These findings suggest that among PBN taste neurons, time-dependent
      increases in mutual information can arise from stimulus- and neuron-specific
      differences in response envelope during the initial dynamic period. A stable rate
      code predominates in later epochs.

PMID- 24124598
TI  - Over-expression of the ATP5J gene correlates with cell migration and 5
      fluorouracil sensitivity in colorectal cancer.
AB  - Recently we found that ATP5J was over-expressed in tissue samples from patients
      with colorectal cancer. However, the clinical significance and function of the
      over-expression of ATP5J in these patients remains unclear. We investigated these
      issues in the current study. Our results indicated that expression of ATP5J was
      significantly higher in colorectal cancer tissue than in adjacent tissue, and it
      was also significantly higher in metastatic lymph nodes than in primary cancer
      tissue (P<0.05). A correlation between ATP5J expression and tumor differentiation
      was detected, but no correlation with gender, age, T stage, lymph node
      metastasis, or survival status was observed. Down-regulation of ATP5J expression
      attenuated the ability of cell migration and increased the sensitivity to 5
      fluorouracil (5-Fu) in cells of the DLD1 cell line. Inversely, up-regulation of
      ATP5J expression enhanced cell migration and decreased 5-Fu sensitivity,
      suggesting that the function of ATP5J in colorectal cancer might involve cell
      migration and 5-Fu sensitivity.

PMID- 24124599
TI  - Saccharomyces cerevisiae-based platform for rapid production and evaluation of
      eukaryotic nutrient transporters and transceptors for biochemical studies and
      crystallography.
AB  - To produce large quantities of high quality eukaryotic membrane proteins in
      Saccharomyces cerevisiae, we modified a high-copy vector to express membrane
      proteins C-terminally-fused to a Tobacco Etch Virus (TEV) protease detachable
      Green Fluorescent Protein (GFP)-8His tag, which facilitates localization,
      quantification, quality control, and purification. Using this expression system
      we examined the production of a human glucose transceptor and 11 nutrient
      transporters and transceptors from S. cerevisiae that have not previously been
      overexpressed in S. cerevisiae and purified. Whole-cell GFP-fluorescence showed
      that induction of GFP-fusion synthesis from a galactose-inducible promoter at 15
      degrees C resulted in stable accumulation of the fusions in the plasma membrane
      and in intracellular membranes. Expression levels of the 12 fusions estimated by
      GFP-fluorescence were in the range of 0.4 mg to 1.7 mg transporter pr. liter cell
      culture. A detergent screen showed that n-dodecyl-beta-D-maltopyranoside (DDM) is
      acceptable for solubilization of the membrane-integrated fusions. Extracts of
      solubilized membranes were prepared with this detergent and used for
      purifications by Ni-NTA affinity chromatography, which yielded partially purified
      full-length fusions. Most of the fusions were readily cleaved at a TEV protease
      site between the membrane protein and the GFP-8His tag. Using the yeast
      oligopeptide transporter Ptr2 as an example, we further demonstrate that almost
      pure transporters, free of the GFP-8His tag, can be achieved by TEV protease
      cleavage followed by reverse immobilized metal-affinity chromatography. The
      quality of the GFP-fusions was analysed by fluorescence size-exclusion
      chromatography. Membranes solubilized in DDM resulted in preparations containing
      aggregated fusions. However, 9 of the fusions solubilized in DDM in presence of
      cholesteryl hemisuccinate and specific substrates, yielded monodisperse
      preparations with only minor amounts of aggregated membrane proteins. In
      conclusion, we developed a new effective S. cerevisiae expression system that may
      be used for production of high-quality eukaryotic membrane proteins for
      functional and structural analysis.

PMID- 24124600
TI  - Role of an indole-thiazolidine molecule PPAR pan-agonist and COX inhibitor on
      inflammation and microcirculatory damage in acute gastric lesions.
AB  - The present study aimed to show the in vivo mechanisms of action of an indole
      thiazolidine molecule peroxisome-proliferator activated receptor pan-agonist
      (PPAR pan) and cyclooxygenase (COX) inhibitor, LYSO-7, in an ethanol/HCl-induced
      (Et/HCl) gastric lesion model. Swiss male mice were treated with vehicle, LYSO-7
      or Bezafibrate (p.o.) 1 hour before oral administration of Et/HCl (60%/0.03M). In
      another set of assays, animals were injected i.p. with an anti-granulocyte
      antibody, GW9962 or L-NG-nitroarginine methyl ester (L-NAME) before treatment.
      One hour after Et/HCl administration, neutrophils were quantified in the blood
      and bone marrow and the gastric microcirculatory network was studied in situ. The
      gastric tissue was used to quantify the percentage of damaged area, as well as
      myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), endothelial nitric
      oxide synthase (eNOS) protein and PPARgamma protein and gene expression. Acid
      secretion was evaluated by the pylorus ligation model. LYSO-7 or Bezafibrate
      treatment reduced the necrotic area. LYSO-7 treatment enhanced PPARgamma gene and
      protein expression in the stomach, and impaired local neutrophil influx and
      stasis of the microcirculatory network caused by Et/HCl administration. The
      effect seemed to be due to PPARgamma agonist activity, as the LYSO-7 effect was
      abolished in GW9962 pre-treated mice. The reversal of microcirculatory stasis,
      but not neutrophil influx, was mediated by nitric oxide (NO), as L-NAME pre
      treatment abolished the LYSO-7-mediated reestablishment of microcirculatory blood
      flow. This effect may depend on enhanced eNOS protein expression in injured
      gastric tissue. The pH and concentration of H(+) in the stomach were not modified
      by LYSO-7 treatment. In addition, LYSO-7 may induce less toxicity, as 28 days of
      oral treatment did not induce weight loss, as detected in pioglitazone treated
      mice. Thus, we show that LYSO-7 may be an effective treatment for gastric lesions
      by controlling neutrophil influx and microcirculatory blood flow mediated by NO.

PMID- 24124601
TI  - Establishment of self-renewable GM-CSF-dependent immature macrophages in vitro
      from murine bone marrow.
AB  - Macrophages play a key role in the innate immune system. Macrophages are thought
      to originate from hematopoietic precursors or the yolk sac. Here, we describe the
      in vitro establishment of self-renewable GM-CSF-dependent immature macrophages
      (GM-IMs) from murine bone marrow (BM). GM-IMs grow continuously in vitro in
      conditioned medium containing GM-CSF. The immunophenotype of GM-IMs is
      F4/80(high) CD11b(high) CD11c(low) Ly6C(low). By comparing gene expression in GM
      IMs and BM dendritic cells, we found that GM-IMs expressed lower levels of
      chemokines, cytokines and their receptors. GM-IMs are round in shape, attach
      loosely to non-coated culture dishes and have a marked phagocytic capacity. These
      results indicate that GM-IMs are macrophage precursor cells. Following
      stimulation with LPS, monocyte-like GM-IMs converted to flat macrophage-like
      cells that tightly adhered to non-coated culture dishes and produced pro
      inflammatory cytokines TNFalpha, IL-6 and IL-1beta. These results indicated that
      GM-IMs differentiated to M1 pro-inflammatory macrophages. This was confirmed by
      stimulation of GM-IMs with IFNgamma, an inducer of M1 markers. GM-IMs showed
      enhanced expression of M2 macrophage markers such as Arg1 and Retnla following
      stimulation by Th2 cytokines IL-4 and IL-13. When GM-IMs were injected into mice
      at sites of wounding, wound repair was enhanced. These results indicate that GM
      IMs can differentiate to M2 macrophages. When GM-IMs were injected into
      clodronate-treated mice, they induced resident macrophage proliferation by
      producing M-CSF. In conclusion we have established self-renewable GM-CSF
      dependent immature macrophages in vitro from murine BM, which differentiate to M1
      or M2 macrophages. 

PMID- 24124602
TI  - Dopa-responsive dystonia: functional analysis of single nucleotide substitutions
      within the 5' untranslated GCH1 region.
AB  - BACKGROUND: Mutations in the GCH1 gene are associated with childhood onset, dopa
      responsive dystonia (DRD). Correct diagnosis of DRD is crucial, given the
      potential for complete recovery once treated with L-dopa. The majority of DRD
      associated mutations lie within the coding region of the GCH1 gene, but three
      additional single nucleotide sequence substitutions have been reported within the
      5' untranslated (5'UTR) region of the mRNA. The biologic significance of these
      5'UTR GCH1 sequence substitutions has not been analyzed. METHODOLOGY/PRINCIPAL
      FINDINGS: Luciferase reporter assays, quantitative real time PCR and RNA decay
      assays, combined with bioinformatics, revealed a pathogenic 5'UTR GCH1
      substitution. The +142C>T single nucleotide 5'UTR substitution that segregates
      with affected status in DRD patients, substantially attenuates translation
      without altering RNA expression levels or stability. The +142C>T substitution
      disrupts translation most likely by creating an upstream initiation start codon
      (uAUG) and an upstream open reading frame (uORF). CONCLUSIONS/SIGNIFICANCE: This
      is the first GCH1 regulatory substitution reported to act at a post
      transcriptional level, increasing the list of genetic diseases caused by abnormal
      translation and reaffirming the importance of investigating potential regulatory
      substitutions in genetic diseases.

PMID- 24124603
TI  - CD105 (endoglin)-negative murine mesenchymal stromal cells define a new
      multipotent subpopulation with distinct differentiation and immunomodulatory
      capacities.
AB  - Administration of in vitro expanded mesenchymal stromal cells (MSCs) represents a
      promising therapy for regenerative medicine and autoimmunity. Both mouse and
      human MSCs ameliorate autoimmune disease in syn-, allo- and xenogeneic settings.
      However, MSC preparations are heterogeneous which impairs their therapeutic
      efficacy and endorses variability between experiments. This heterogeneity has
      also been a main hurdle in translating experimental MSC data from mouse models to
      human patients. The objective of the present manuscript has been to further
      characterize murine MSCs (mMSCs) with the aim of designing more efficient and
      specific MSC-based therapies. We have found that mMSCs are heterogeneous for
      endoglin (CD105) expression and that this heterogeneity is not due to different
      stages of MSC differentiation. CD105 is induced on a subpopulation of mMSCs early
      upon in vitro culture giving rise to CD105(+) and CD105(-) MSCs. CD105(+) and
      CD105(-) mMSCs represent independent subpopulations that maintain their
      properties upon several passages. CD105 expression on CD105(+) mMSCs was affected
      by passage number and cell confluency while CD105(-) mMSCs remained negative. The
      CD105(+) and CD105(-) mMSC subpopulations had similar growth potential and
      expressed almost identical mMSC markers (CD29(+)CD44(+)Sca1 (+) MHC-I(+) and
      CD45(-)CD11b(-)CD31(-)) but varied in their differentiation and immunoregulatory
      properties. Interestingly, CD105(-) mMSCs were more prone to differentiate into
      adipocytes and osteocytes and suppressed the proliferation of CD4(+) T cells more
      efficiently compared to CD105(+) mMSCs. Based on these studies we propose to
      redefine the phenotype of mMSCs based on CD105 expression.

PMID- 24124604
TI  - Stratifin (14-3-3 sigma) limits plakophilin-3 exchange with the desmosomal
      plaque.
AB  - Desmosomes are prominent cell-cell adhesive junctions in stratified squamous
      epithelia and disruption of desmosomal adhesion has been shown to have dramatic
      effects on the function and integrity of these tissues. During normal physiologic
      processes, such as tissue development and wound healing, intercellular adhesion
      must be modified locally to allow coordinated cell movements. The mechanisms that
      control junction integrity and adhesive strength under these conditions are
      poorly understood. We utilized a proteomics approach to identify plakophilin-3
      associated proteins and identified the 14-3-3 family member stratifin. Stratifin
      interacts specifically with plakophilin-3 and not with other plakophilin isoforms
      and mutation analysis demonstrated the binding site includes serine 285 in the
      amino terminal head domain of plakophilin-3. Stratifin interacts with a
      cytoplasmic pool of plakophilin-3 and is not associated with the desmosome in
      cultured cells. FRAP analysis revealed that decreased stratifin expression leads
      to an increase in the exchange rate of cytoplasmic plakophilin-3/GFP with the
      pool of plakophilin-3/GFP in the desmosome resulting in decreased desmosomal
      adhesion and increased cell migration. We propose a model by which stratifin
      plays a role in regulating plakophilin-3 incorporation into the desmosomal plaque
      by forming a plakophilin-3 stratifin complex in the cytosol and thereby affecting
      desmosome dynamics in squamous epithelial cells.

PMID- 24124605
TI  - A mitochondrial phylogeny and biogeographical scenario for Asiatic water shrews
      of the genus Chimarrogale: implications for taxonomy and low-latitude migration
      routes.
AB  - The six species and three subspecies in the genus Chimarrogale (Soricomorpha:
      Soricidae) are commonly referred to as Asiatic water shrews. The Chimarrogale are
      the most widely distributed group of Nectogaline shrews, extending throughout the
      Oriental region and Japan. Because of the limited numbers of specimens available
      for study, the phylogenetic relationships and biogeographical history of this
      genus have not been comprehensively discussed. We used mitochondrial cytochrome b
      gene sequences to estimate phylogenetic relationships and divergence times among
      four Chimarrogale species, including all three subspecies of Chimarrogale
      himalayica. We also conducted a species delimitation analysis and tested two
      alternative migration scenarios in Asia through species distribution modeling and
      a reconstruction of the ancestral distribution. Here, we present the first
      proposed hypothesis regarding the Asiatic water shrew phylogeny and reveal ten
      putative species within the four recognized species. Distinct phylogenetic
      statuses of Chimarrogale phaeura, Chimarrogale platycephala, and Chimarrogale
      styani were confirmed. Chimarrogale himalayica was strongly supported as
      paraphyletic. We suggest that three subspecies of Chimarrogale himalayica should
      be reconsidered as distinct species. However, these suggestions must be
      considered with caution because only a single locus of a mtDNA gene was used.
      Four additional putative species, possibly distributed in central southwestern
      China and Taiwan, are currently undescribed; therefore, comprehensive
      morphological analyses are warranted to test their taxonomic statuses. The
      estimated molecular divergence times indicated that rapid speciation occurred
      during the early Pliocene, and current distribution patterns may have been
      affected by global cooling during the Pliocene/Pleistocene boundary.
      Reconstruction of the ancestral distribution and species distribution modeling
      for Asiatic water shrews revealed a low-latitude migration route over which
      ancestral Chimarrogale migrated from Europe via Central Asia to their current
      distribution. Our results demonstrated that Asiatic water shrews could have
      evolved throughout the low-latitude migration route from Europe to East and
      Southeast Asia.

PMID- 24124606
TI  - Genetic analysis of Bordetella pertussis isolates from the 2008-2010 pertussis
      epidemic in Japan.
AB  - A large pertussis epidemic occurred between 2008 and 2010 in Japan. To
      investigate epidemic strains, we analyzed 33 Bordetella pertussis isolates from
      the epidemic period by sequencing virulence-associated genes (fim3, ptxP, ptxA,
      and prn) and performing multilocus variable-number tandem repeat analysis (MLVA),
      and compared these results with those of 101 isolates from non-epidemic, earlier
      and later time periods. DNA sequencing of the fim3 allele revealed that the
      frequency of fim3B was 4.3%, 12.8%, 30.3%, and 5.1% within isolates in 2002-2004,
      2005-2007, 2008-2010, and 2011-2012, respectively. The isolation rate of the
      fim3B strain therefore temporarily increased during the epidemic period 2008
      2010. In contrast, the frequencies of the virulence-associated allelic variants,
      ptxP3, ptxA1, and prn2, increased with time during overall study period,
      indicating that these variants were not directly involved in the occurrence of
      the 2008-2010 epidemic. MLVA genotyping in combination with analysis of allele
      types showed that the prevalence of an MT27d strain temporarily increased in the
      epidemic period, and that this strain carried virulence-associated allelic
      variants (fim3B, ptxP3, ptxA1, and prn2) also identified in recent epidemic
      strains of Australia, Europe, and the US. Phenotypic analyses revealed that the
      serotype Fim3 strain was predominant (>= 87%) during all the periods studied, and
      that the frequency of adhesion pertactin (Prn) non-expressing B. pertussis
      decreased by half in the epidemic period. All MT27d strains expressed Prn and
      Fim3 proteins, suggesting that B. pertussis MT27d strains expressing Prn and
      Fim3B have the potential to cause large epidemics worldwide.

PMID- 24124607
TI  - Age-dependent astroglial vulnerability to hypoxia and glutamate: the role for
      erythropoietin.
AB  - Extracellular accumulation of toxic concentrations of glutamate (Glu) is a
      hallmark of many neurodegenerative diseases, often accompanied by hypoxia and
      impaired metabolism of this neuromediator. To address the question whether the
      multifunctional neuroprotective action of erythropoietin (EPO) extends to the
      regulation of extracellular Glu-level and is age-related, young and culture-aged
      rat astroglial primary cells (APC) were simultaneously treated with 1mM Glu
      and/or human recombinant EPO under normoxic and hypoxic conditions (NC and HC).
      EPO increased the Glu uptake by astrocytes under both NC and especially upon HC
      in culture-aged APC (by 60%). Moreover, treatment with EPO up-regulated the
      activity of glutamine synthetase (GS), the expression of glutamate-aspartate
      transporter (GLAST) and the level of EPO mRNA. EPO alleviated the Glu- and
      hypoxia-induced LDH release from astrocytes. These protective EPO effects were
      concentration-dependent and they were strongly intensified with age in culture.
      More than a 4-fold increase in apoptosis and a 2-fold decrease in GS enzyme
      activity was observed in APC transfected with EPO receptor (EPOR)-siRNA. Our in
      vivo data show decreased expression of EPO and a strong increase of EPOR in brain
      homogenates of APP/PS1 mice and their wild type controls during aging. Comparison
      of APP/PS1 and age-matched WT control mice revealed a stronger expression of EPOR
      but a weaker one of EPO in the Alzheimer's disease (AD) model mice. Here we show
      for the first time the direct correlation between the extent of differentiation
      (age) of astrocytes and the efficacy of EPO in balancing extracellular glutamate
      clearance and metabolism in an in-vitro model of hypoxia and Glu-induced
      astroglial injury. The clinical relevance of EPO and EPOR as markers of brain
      cells vulnerability during aging and neurodegeneration is evidenced by remarkable
      changes in their expression levels in a transgenic model of AD and their WT
      controls.

PMID- 24124608
TI  - GSTT1 copy number gain and ZNF overexpression are predictors of poor response to
      imatinib in gastrointestinal stromal tumors.
AB  - Oncogenic mutations in gastrointestinal stromal tumors (GISTs) predict prognosis
      and therapeutic responses to imatinib. In wild-type GISTs, the tumor-initiating
      events are still unknown, and wild-type GISTs are resistant to imatinib therapy.
      We performed an association study between copy number alterations (CNAs)
      identified from array CGH and gene expression analyses results for four wild-type
      GISTs and an imatinib-resistant PDGFRA D842V mutant GIST, and compared the
      results to those obtained from 27 GISTs with KIT mutations. All wild-type GISTs
      had multiple CNAs, and CNAs in 1p and 22q that harbor the SDHB and GSTT1 genes,
      respectively, correlated well with expression levels of these genes. mRNA
      expression levels of all SDH gene subunits were significantly lower (P<=0.041),
      whereas mRNA expression levels of VEGF (P=0.025), IGF1R (P=0.026), and ZNFs
      (P<0.05) were significantly higher in GISTs with wild-type/PDGFRA D842V mutations
      than GISTs with KIT mutations. qRT-PCR validation of the GSTT1 results in this
      cohort and 11 additional malignant GISTs showed a significant increase in the
      frequency of GSTT1 CN gain and increased mRNA expression of GSTT1 in wild
      type/PDGFRA D842V GISTs than KIT-mutant GISTs (P=0.033). Surprisingly, all four
      malignant GISTs with KIT exon 11 deletion mutations with primary resistance to
      imatinib had an increased GSTT1 CN and mRNA expression level of GSTT1. Increased
      mRNA expression of GSTT1 and ZNF could be predictors of a poor response to
      imatinib. Our integrative approach reveals that for patients with wild-type (or
      imatinib-resistant) GISTs, attempts to target VEGFRs and IGF1R may be reasonable
      options.

PMID- 24124609
TI  - Relationship between numerous mast cells and early follicular development in
      neonatal MRL/MpJ mouse ovaries.
AB  - In the neonatal mouse ovary, clusters of oocytes called nests break into smaller
      cysts and subsequently form individual follicles. During this period, we found
      numerous mast cells in the ovary of MRL/MpJ mice and investigated their
      appearance and morphology with follicular development. The ovarian mast cells,
      which were already present at postnatal day 0, tended to localize adjacent to the
      surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the
      greatest number of ovarian mast cells. Ovarian mast cells were also found in
      DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA,
      and ICR mice. The ovarian mast cells expressed connective tissue mast cell
      markers, although mast cells around the surface epithelium also expressed a
      mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into
      the oocyte nests and directly contacted the compressed and degenerated oocytes.
      In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than
      in the other strains, and the number of oocytes showed a positive correlation
      with the number of ovarian mast cells. The gene expression of a mast cell marker
      also correlated with the expression of an oocyte nest marker, suggesting a link
      between the appearance of ovarian ? 4mast cells and early follicular development.
      Furthermore, the expression of follicle developmental markers was significantly
      higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the
      appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice,
      and that ovarian mast cells participate in early follicular development,
      especially nest breakdown. 

PMID- 24124610
TI  - New insights into the microvascular mechanisms of drag reducing polymers: effect
      on the cell-free layer.
AB  - Drag-reducing polymers (DRPs) significantly increase blood flow, tissue
      perfusion, and tissue oxygenation in various animal models. In rectangular
      channel microfluidic systems, DRPs were found to significantly reduce the near
      wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC)
      into microchannel branches. In the current study we further investigated the
      mechanism by which DRP enhances microvascular perfusion. We studied the effect of
      various concentrations of DRP on RBC distribution in more relevant round
      microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo.
      In round microchannels hematocrit was measured in parent and daughter branch at
      baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the
      plasma skimming effect in the daughter branch was eliminated, as parent and
      daughter branch hematocrit were equivalent, compared to a significantly lowered
      hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL
      was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6
      +/- 1.7 um. In the control group (saline, N=6) there was a significant increase
      in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5)
      reduced CFL significantly compared to corresponding baseline and the control
      group. After DRP administration the CFL reduced to about 85% of baseline at 5,
      15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro
      findings demonstrate that DRPs induce a reduction in CFL width and plasma
      skimming in the microvasculature. This may lead to an increase of RBC flux into
      the capillary bed, and thus explain previous observations of a DRP mediated
      enhancement of capillary perfusion.

PMID- 24124611
TI  - Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell
      lung cancer cells by targeting EGFR/VEGFR2 signaling pathways.
AB  - Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
      receptor 2 (VEGFR2) have emerged as two effective clinical targets for non-small
      cell lung cancer (NSCLC). In the present study, we found that delphinidin, an
      anthocyanidin, present in pigmented fruits and vegetables, is a potent inhibitor
      of both EGFR and VEGFR2 in NSCLC cells that overexpress EGFR/VEGFR2. Using these
      cells, we next determined the effects of delphinidin on cell growth and apoptosis
      in vitro and on tumor growth and angiogenesis in vivo. Delphinidin (5-60 uM)
      treatment of NSCLC cells inhibited the activation of PI3K, and phosphorylation of
      AKT and MAPKs. Additionally, treatment of NSCLC cells with delphinidin resulted
      in inhibition of cell growth without having significant toxic effects on normal
      human bronchial epithelial cells. Specifically, treatment of NCI-H441 and SK-MES
      1 cells with delphindin (5-60 uM) resulted in (i) cleavage of PARP protein, (ii)
      activation of caspase-3 and -9, (iii) downregulation of anti-apoptotic proteins
      (Bcl2, Bcl-xL and Mcl-1), (iv) upregulation of pro-apoptotic proteins (Bax and
      Bak), and (v) decreased expression of PCNA and cyclin D1. Furthermore, in athymic
      nude mice subcutaneously implanted with human NSCLC cells, delphinidin treatment
      caused a (i) significant inhibition of tumor growth, (ii) decrease in the
      expression of markers for cell proliferation (Ki67 and PCNA) and angiogenesis
      (CD31 and VEGF), and (iii) induction of apoptosis, when compared with control
      mice. Based on these observations, we suggest that delphinidin, alone or as an
      adjuvant to current therapies, could be used for the management of NSCLC,
      especially those that overexpress EGFR and VEGFR2. 

PMID- 24124612
TI  - Beneficial effects of cod protein on inflammatory cell accumulation in rat
      skeletal muscle after injury are driven by its high levels of arginine, glycine,
      taurine and lysine.
AB  - We have shown that feeding cod protein, which is rich in anti-inflammatory
      arginine, glycine, and taurine, may beneficially modulate the inflammatory
      response during recovery following skeletal muscle injury; however it is unknown
      if these amino acids are responsible for this effect. This study was designed to
      assess whether supplementing casein with an amino acid mixture composed of
      arginine, glycine, taurine and lysine, matching their respective levels in cod
      protein, may account for the anti-inflammatory effect of cod protein. Male Wistar
      rats were fed isoenergetic diets containing either casein, cod protein, or casein
      supplemented with L-arginine (0.45%), glycine (0.43%), L-taurine (0.17%) and L
      lysine (0.44%) (casein+). After 21 days of ad libitum feeding, one tibialis
      anterior muscle was injured with 200 ul bupivacaine while the saline-injected
      contra-lateral tibialis anterior was served as sham. Cod protein and casein+
      similarly modulated the inflammation as they decreased COX-2 level at day 2 post
      injury (cod protein, p=0.014; casein+, p=0.029) and ED1(+) macrophage density at
      days 2 (cod protein, p=0.012; casein+, p<0.0001), 5 (cod protein, p=0.001;
      casein+, p<0.0001) and 14 (cod protein, p<0.0001; casein+, p<0.0001) post-injury,
      and increased ED2(+) macrophage density at days 5 (cod protein, p<0.0001;
      casein+, p=0.006), 14 (cod protein, p=0.001; casein+, p<0.002) and 28 (cod
      protein, p<0.009; casein+, p<0.005) post-injury compared with casein.
      Furthermore, cod protein up-regulated (p=0.037) whereas casein+ tended to up
      regulate (p=0.062) myogenin expression at day 5 post-injury compared with casein.
      In the cod protein-fed group, these changes resulted in greater muscle mass at
      days 14 (p=0.002), and 28 (p=0.001) post-injury and larger myofiber cross
      sectional area at day 28 post-injury compared with casein (p=0.012). No such
      effects were observed with casein+. These data indicate that anti-inflammatory
      actions of cod protein, contrary to its effect on muscle mass recovery, are
      driven by its high levels of arginine, glycine, taurine and lysine.

PMID- 24124613
TI  - Knowledge claims, jurisdictional control and professional status: the case of
      nurse prescribing.
AB  - Over the past decades, professional boundaries in health care have come under
      pressure, and the expansion of prescriptive authority to include nurses touches
      on issues of professional domains and interprofessional competition. Knowledge
      claims play an important role in achieving jurisdictional control. Knowledge can
      take on multiple forms, ranging from indeterminate to technical (I/T ratio) and
      from everyday to exclusive knowledge. To investigate the interrelatedness of
      jurisdiction, knowledge claims and professional status, we examine which
      knowledge claims were made by the medical and nursing professions in the
      Netherlands to secure or obtain, respectively, jurisdictional control over
      prescribing, and which form this knowledge took. The study is based on thirteen
      semi-structured stakeholder interviews and an extensive document analysis. We
      found that the nursing profession in its knowledge claims strongly emphasized the
      technicality and everyday knowledge character of the prescribing task, by
      asserting that nurses were already prescribing medicines, albeit on an illegal
      basis. Their second claim focused on the indeterminate knowledge skills of nurses
      and stated that nurse prescribing would do justice to nurses' skills and
      expertise. This is a strong claim in a quest for (higher) professional status.
      Results showed that the medical profession initially proclaimed that prescribing
      should be reserved for doctors as it is a task requiring medical knowledge, i.e.
      indeterminate knowledge. Gradually, however, the medical profession adjusted its
      claims and tried to reduce nurse prescribing to a task almost exclusively based
      on technicality knowledge, among others by stating that nurses could prescribe in
      routine cases, which would generate little professional status. By investigating
      the form that professional knowledge claims took, this study was able to show the
      interconnectedness of jurisdictional control, knowledge claims and professional
      status. Knowledge claims are not mere rhetoric, but actively influence the
      everyday realities of professional status, interprofessional competition and
      jurisdictional division between professions. 

PMID- 24124614
TI  - Mammosphere formation in breast carcinoma cell lines depends upon expression of E
      cadherin.
AB  - Tumors are heterogeneous at the cellular level where the ability to maintain
      tumor growth resides in discrete cell populations. Floating sphere-forming assays
      are broadly used to test stem cell activity in tissues, tumors and cell lines.
      Spheroids are originated from a small population of cells with stem cell features
      able to grow in suspension culture and behaving as tumorigenic in mice. We tested
      the ability of eleven common breast cancer cell lines representing the major
      breast cancer subtypes to grow as mammospheres, measuring the ability to maintain
      cell viability upon serial non-adherent passage. Only MCF7, T47D, BT474, MDA-MB
      436 and JIMT1 were successfully propagated as long-term mammosphere cultures,
      measured as the increase in the number of viable cells upon serial non-adherent
      passages. Other cell lines tested (SKBR3, MDA-MB-231, MDA-MB-468 and MDA-MB-435)
      formed cell clumps that can be disaggregated mechanically, but cell viability
      drops dramatically on their second passage. HCC1937 and HCC1569 cells formed
      typical mammospheres, although they could not be propagated as long-term
      mammosphere cultures. All the sphere forming lines but MDA-MB-436 express E
      cadherin on their surface. Knock down of E-cadherin expression in MCF-7 cells
      abrogated its ability to grow as mammospheres, while re-expression of E-cadherin
      in SKBR3 cells allow them to form mammospheres. Therefore, the mammosphere assay
      is suitable to reveal stem like features in breast cancer cell lines that express
      E-cadherin.

PMID- 24124615
TI  - Dissection of the beta-globin replication-initiation region reveals specific
      requirements for replicator elements during gene amplification.
AB  - Gene amplification plays a pivotal role in malignant transformation of human
      cells. A plasmid with both a mammalian replication-initiation region
      (IR)/origin/replicator and a nuclear matrix-attachment region (MAR) is
      spontaneously amplified in transfected cells by a mechanism that involves
      amplification at the extrachromosomal site, followed by amplification at the
      chromosomal arm, ultimately generating a long homogeneously staining region
      (HSR). Several observations suggest that replication initiation from IR sequences
      might mediate amplification. To test this idea, we previously dissected c-myc and
      DHFR IRs to identify the minimum sequence required to support amplification. In
      this study, we applied an improved analysis that discriminates between two
      amplification steps to the beta-globin RepP IR, which contains separate elements
      already known to be essential for initiation on the chromosome arm. The IR
      sequence was required at least for the extrachromosomal amplification step. In
      addition to the vector-encoded MAR, amplification also required an AT-rich region
      and a MAR-like element, consistent with the results regarding replicator activity
      on the chromosome. However, amplification did not require the AG-rich tract
      necessary for replicator activity, but instead required a novel sequence
      containing another AG-rich tract. The differential sequence requirement might be
      a consequence of extrachromosomal replication. 

PMID- 24124616
TI  - The impact of nationwide education program on clinical practice in sepsis care
      and mortality of severe sepsis: a population-based study in Taiwan.
AB  - OBJECTIVES: We investigated the effect of a nationwide educational program
      following surviving sepsis campaign (SSC) guidelines. Physicians' clinical
      practice in sepsis care and patient mortality rate for severe sepsis were
      analyzed using a nationally representative cohort. METHODS: Hospitalizations for
      severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan's
      National Health Insurance Research Database (NHIRD), and trends in sepsis
      incidence and mortality rates were analyzed. A before-and-after study design was
      used to evaluate changes in the utilization rates of SSC items and changes in
      severe sepsis mortality rates occurred after a national education program
      conducted by the Joint Taiwan Critical Care Medicine Committee since 2004. A
      total of 39,706 hospitalizations were analyzed, which consisted of a pre
      intervention cohort of 14,848 individuals (2000-2003) and a post-intervention
      cohort of 24,858 individuals (2005-2008). RESULTS: The incidence rate of severe
      sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000
      individuals in 2008. The cumulative mortality rate decreased slightly from 48.2%
      for the pre-intervention cohort to 45.9% for the post-intervention cohort. The
      utilization rates of almost all SSC items changed significantly between the pre
      intervention and post-intervention cohorts. These changes of utilization rates
      were found to be associated with mild reduction in mortality rate. CONCLUSION:
      The nationwide education program through a national professional society has a
      significant impact on physicians' clinical practice and resulted in a slight but
      significant reduction of severe sepsis mortality rate.

PMID- 24124617
TI  - Ewing sarcoma cells secrete EWS/Fli-1 fusion mRNA via microvesicles.
AB  - Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant
      neoplasms that most often affect children and young adults in the first 2 decades
      of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24;
      12), is detected in 95% of ES patients. Recently, it was validated that cells
      emit a heterogeneous mixture of vesicular, organelle-like structures
      (microvesicles, MVs) into their surroundings including blood and body fluids, and
      that these MVs contain a selected set of tumor-related proteins and high levels
      of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma
      specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying
      t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of
      the blood samples from mice inoculated with xenografts of TC135 or A673 cells.
      These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive
      diagnostic marker for specific cases of Ewing sarcoma.

PMID- 24124618
TI  - Improving acetate tolerance of Escherichia coli by rewiring its global regulator
      cAMP receptor protein (CRP).
AB  - The presence of acetate exceeding 5 g/L is a major concern during E. coli
      fermentation due to its inhibitory effect on cell growth, thereby limiting high
      density cell culture and recombinant protein production. Hence, engineered E.
      coli strains with enhanced acetate tolerance would be valuable for these
      bioprocesses. In this work, the acetate tolerance of E. coli was much improved by
      rewiring its global regulator cAMP receptor protein (CRP), which is reported to
      regulate 444 genes. Error-prone PCR method was employed to modify crp and the
      mutagenesis libraries (~3*10(6)) were subjected to M9 minimal medium supplemented
      with 5-10 g/L sodium acetate for selection. Mutant A2 (D138Y) was isolated and
      its growth rate in 15 g/L sodium acetate was found to be 0.083 h(-1), much higher
      than that of the control (0.016 h(-1)). Real-time PCR analysis via OpenArray((r))
      system revealed that over 400 CRP-regulated genes were differentially expressed
      in A2 with or without acetate stress, including those involved in the TCA cycle,
      phosphotransferase system, etc. Eight genes were chosen for overexpression and
      the overexpression of uxaB was found to lead to E. coli acetate sensitivity.

PMID- 24124619
TI  - Ecological consequences of sediment on high-energy coral reefs.
AB  - Sediments are widely accepted as a threat to coral reefs but our understanding of
      their ecological impacts is limited. Evidence has suggested that benthic
      sediments bound within the epilithic algal matrix (EAM) suppress reef fish
      herbivory, a key ecological process maintaining reef resilience. An experimental
      combination of caging and sediment addition treatments were used to investigate
      the effects of sediment pulses on herbivory and EAMs and to determine whether
      sediment addition could trigger a positive-feedback loop, leading to deep,
      sediment-rich turfs. A 1-week pulsed sediment addition resulted in rapid
      increases in algal turf length with effects comparable to those seen in herbivore
      exclusion cages. Contrary to the hypothesised positive-feedback mechanism,
      benthic sediment loads returned to natural levels within 3 weeks, however, the
      EAM turfs remained almost 60% longer for at least 3 months. While reduced
      herbivore density is widely understood to be a major threat to reefs, we show
      that acute disturbances to reef sediments elicit similar ecological responses in
      the EAM. With reefs increasingly threatened by both reductions in herbivore
      biomass and altered sediment fluxes, the development of longer turfs may become
      more common on coral reefs. 

PMID- 24124620
TI  - Assessment of dynamic cerebral autoregulation in patients with basilar artery
      stenosis.
AB  - BACKGROUND AND AIMS: Previous studies have shown impaired cerebral autoregulation
      (CA) in carotid and middle cerebral artery (MCA) stenosis/occlusion. Little is
      known about CA in patients with basilar artery (BA) stenosis. We therefore
      investigated dynamic CA patterns in BA stenosis using transfer function analysis
      (TFA). METHODS: We measured spontaneous oscillations of blood flow velocity
      (CBFV) in the right posterior cerebral artery (PCA), and left MCA and mean
      arterial pressure (ABP) continuously in 25 patients with BA stenosis (moderate
      n=16 with 50-69% occlusion and severe n=9 with >= 70% occlusion) and 22 healthy
      volunteers in supine position during 6 circles per minute deep breath. Analysis
      was based on the 'black-box' model of transfer function deriving phase and gain
      in both PCA and MCA. RESULTS: Though changes of phase shift and gain between the
      patients and healthy controls were observed in MCA, the differences are however
      not significant. Phase shift in PCA was significantly decreased in severe
      stenosis when comparing with healthy controls and moderate stenosis (4.2 +/- 34.2
      degrees  VS 41.1 +/- 40.4 degrees , 4.2 +/- 34.2 degrees  VS 34.2 +/- 27.2
      degrees , both p<0.05), whilst the gain in PCA is increased for moderate BA
      stenosis and decreased for severe BA stenosis. Furthermore, we found that phase
      shift were almost abolished in patients with ischemic stroke who developed
      unfavorable clinical outcome (mRs>2) on the 90 days after stroke onset.
      CONCLUSION: Dynamic CA in PCA reduces in patients with severe BA stenosis and
      those with ischemic stroke who present poor outcome in 90 days after stroke
      onset. Phase shift might be a sensitive index prompting impaired CA in posterior
      circulation.

PMID- 24124621
TI  - Herpesvirus-associated central nervous system diseases after allogeneic
      hematopoietic stem cell transplantation.
AB  - Herpesvirus infections of the central nervous system (CNS) are associated with
      encephalitis/myelitis and lymphoproliferative diseases in immunocompromised
      individuals. As of now, data of herpesvirus-associated CNS diseases in transplant
      recipients is limited. Hence, in this prospective study, we investigated the
      incidence of herpesvirus-associated CNS diseases and explored the diagnosis of
      these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo
      HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were
      sampled from 58 recipients with herpesvirus-associated diseases or with
      unexplainable CNS manifestations. Results showed that 23 patients were diagnosed
      as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)
      associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5
      herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis
      and 1 varicella zoster virus encephalitis. The median time of diseases onset was
      65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of
      herpesvirus-associated encephalitis/myelitis and post-transplant
      lymphoproliferative disorder (PTLD) was 6.3% +/- 1.9% and 4.1% +/- 1.2%,
      respectively. Of the evaluable cases, CSF cells mainly consisted of
      CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin
      genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with
      encephalitis/myelitis, CSF cells were comprised of different cell populations and
      none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases
      are common in the early stages of allo-HSCT, wherein EBV is the most frequent
      causative virus. The immunophenotypic and clonal analysis of CSF cells might be
      helpful in the differential diagnosis between encephalitis and
      lymphoproliferative diseases.

PMID- 24124623
TI  - Heart rate response to blood pressure variations: sympathetic activation versus
      baroreflex response in patients with end-stage renal disease.
AB  - BACKGROUND: Continuous systolic blood pressure (SBP) and interbeat intervals
      (IBI) recordings reveal sequences of consecutive beats in which SBP and heart
      rate change in opposite direction, representing negative feedback baroreflex
      mechanisms, as well as sequences in which SBP and heart rate change in the same
      direction (non-baroreflex), believed to represent feedforward control mechanisms.
      The present study was undertaken to assess the relationship between baroreflex
      and non-baroreflex sequences in end stage renal insufficiency.
      METHODOLOGY/PRINCIPAL FINDINGS: Continuous beat-to-beat SBP and IBI monitoring
      was performed in patients on chronic hemodialysis (HD, n=72), in age-matched
      patients after renal transplantation (TX, n=41) and healthy (control) individuals
      (C, n=34). The proportion of baroreflex and nonbaroreflex episodes and the b
      coefficients (the regression line slope of SBP-IBI correlation) were determined
      using a newly developed 1 minute sliding window method, the classical sequence
      technique and the "Z" coefficient method. Analysis using the 1 minute sliding
      window showed an increased proportion of baroreflex episodes in controls and HD,
      and predominance of nonbaroreflex episodes in TX. An increased proportion of
      nonbaroreflex episodes in TX patients relative to HD was also revealed by the "Z"
      method. Baroreflex and nonbaroreflex b coefficients obtained by all methods were
      markedly decreased in HD. This alteration was reversed at least partly in TX. In
      HD, both baroreflex and nonbaroreflex b coefficients were inversely correlated to
      age and CRP levels; in TX, the nonbaroreflex b coefficient was influenced by the
      type of calcineurin inhibitor. CONCLUSION/SIGNIFICANCE: Renal status affects the
      contribution of baroreflex and nonbaroreflex mechanisms and the strength of SBP
      IBI relationship. The predominant contribution of nonbaroreflex mechanisms in TX
      may be suggestive of enhanced central sympathetic control. Our data may be
      relevant for understanding of the pathogenesis and selection of appropriate
      treatment of post-transplant hypertension.

PMID- 24124622
TI  - Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH)
      neurons in an estrous cycle and endocannabinoid signaling dependent manner.
AB  - The orexigenic peptide, ghrelin is known to influence function of GnRH neurons,
      however, the direct effects of the hormone upon these neurons have not been
      explored, yet. The present study was undertaken to reveal expression of growth
      hormone secretagogue receptor (GHS-R) in GnRH neurons and elucidate the
      mechanisms of ghrelin actions upon them. Ca(2+)-imaging revealed a ghrelin
      triggered increase of the Ca(2+)-content in GT1-7 neurons kept in a steroid-free
      medium, which was abolished by GHS-R-antagonist JMV2959 (10 uM) suggesting direct
      action of ghrelin. Estradiol (1nM) eliminated the ghrelin-evoked rise of Ca(2+)
      content, indicating the estradiol dependency of the process. Expression of GHS-R
      mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT
      PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous
      than proestrous mice. Ghrelin (40 nM-4 MUM) administration resulted in a
      decreased firing rate and burst frequency of GnRH neurons in metestrous, but not
      in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in
      males. The ghrelin-evoked alterations of the firing parameters were prevented by
      JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In
      metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH
      neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1
      (CB1) antagonist AM251 (1uM) and the intracellularly applied DAG-lipase inhibitor
      THL (10 uM), indicating the involvement of retrograde endocannabinoid signaling.
      These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH
      neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle
      and endocannabinoid dependent manner.

PMID- 24124624
TI  - Lipid Fluid-Gel Phase Transition Induced Alamethicin Orientational Change Probed
      by Sum Frequency Generation Vibrational Spectroscopy.
AB  - Alamethicin has been extensively studied as an antimicrobial peptide (AMP) and is
      widely used as a simple model for ion channel proteins. It has been shown that
      the antimicrobial activity of AMPs is related to their cell membrane orientation,
      which may be influenced by the phase of the lipid molecules in the cell membrane.
      The "healthy" cell membranes contain fluid phase lipids, while gel phase lipids
      can be found in injured or aged cells or in some phase separated membrane
      regions. Thus, investigations on how the phase of the lipids influences the
      membrane orientation of AMPs are important to understand more details regarding
      the AMP's action on cell membranes. In this study, we determined the
      orientational changes of alamethicin molecules associated with planar substrate
      supported single lipid bilayers (serving as model cell membranes) with different
      phases (fluid or gel) as a function of peptide concentration using sum frequency
      generation (SFG) vibrational spectroscopy. The phase changes of the lipid
      bilayers were realized by varying the sample temperature. Our SFG results
      indicated that alamethicin lies down on the surface of fluid and gel phase 1,2
      dimyristoyl(d54)-sn-glycero-3-phosphocholine (d-DMPC) lipid bilayers when the
      lipid bilayers are in contact with a peptide solution with a low concentration of
      0.84 MUM. However, at a medium peptide concentration of 10.80 MUM, alamethicin
      inserts into the fluid phase lipid bilayer. Its orientation switches from a
      transmembrane to an in-plane (or lying down) orientation when the phase of the
      lipid bilayer changes from a fluid state to a gel state. At a high peptide
      concentration of 21.60 MUM, alamethicin adopts a transmembrane orientation while
      associated with both fluid and gel phase lipid bilayers. We also studied the
      structural changes of the fluid and gel phase lipid bilayers upon their
      interactions with alamethicin molecules at different peptide concentrations.

PMID- 24124626
TI  - Pelvic floor complaints in gastroenterology practice: results of a survey in the
      netherlands.
AB  - OBJECTIVE: The pelvic floor is an integrated structure; dysfunctions may lead to
      a wide range of symptoms, involving voiding, defecation and sexual functioning
      (SF). Functional symptoms such as constipation and lower abdominal pain are often
      caused by pelvic floor dysfunction (PFD), and they highly impact the quality of
      life. Multiple specialists are responsible for a specific part of the pelvic
      floor, but its treatment asks for a holistic approach. The authors are still
      unaware of gastroenterologists' knowledge on PFD or whether they are addressing
      pelvic floor complaints in their daily practice. DESIGN: A 42-itemed anonymous
      questionnaire was mailed to all 402 members of the Dutch Society of
      Gastroenterology (gastroenterologists and residents-in-training). RESULTS: 169
      (42%) questionnaires were analysed. Most gastroenterologists address lower
      urinary tract symptoms in their history-taking, 92% in female patients and 84% in
      male patients. When patients indicate irritable bowel syndrome-like complaints,
      more than 60% of the physicians inquire about SF to their female patients,
      compared with 38% inquiries to male patients (p<0.001). A reason not to inquire
      about SF is a lack of knowledge about female and male sexuality (19% and 23%,
      respectively). Forty-six per cent of the respondents regard it rather important
      to receive more training on PFD in male patients versus 61% in female patients.
      CONCLUSION: Awareness of PFD is not yet routinely integrated into the history
      taken by gastroenterologists.

PMID- 24124627
TI  - Mitochondrial Cytochrome c Oxidase subunit 1 Sequence Variation in Prostate
      Cancer.
AB  - PURPOSE: Mitochondrial DNA (mtDNA) gene mutations have been described in nearly
      every adult solid neoplasm including prostate cancer. There are marked racial
      differences in specific inherited mutations within the cytochrome c oxidase
      subunit 1 (COI) gene in individuals with prostate cancer (PCa). The purpose of
      this study was to identify the variation in COI gene sequence in prostate cancer
      patients and to compare the mutations in African and Caucasian Americans.
      MATERIALS AND METHODS: We sequenced the COI gene in DNA derived from peripheral
      blood in 482 prostate cancer patients and 189 controls. All bases that differed
      from the revised Cambridge Reference Sequence (rCRS) were classified as either
      silent (non-amino acid altering) or missense (amino acid altering) and the
      compiled alterations were then compared between races and published reports of
      mutations in this gene in both Caucasian and African-Americans. RESULTS AND
      CONCLUSIONS: We found inherited mtDNA COI missense variants in 8.8% of Caucasian
      prostate cancer patients (vs. 0.0% controls) and 72.8 % of African-American
      prostate cancer patients (vs. 64.3% controls) A total of 144 COI variants were
      identified, of which 30 were missense mutations. Of 482 PCa patients, 116 (24.1%)
      had one or more missense mutations. Further evaluation of this gene and these
      mutations may allow for the identification of genetically at-risk populations.
      The high rate of COI mutations in African-Americans may account for some of the
      racial disparity observed in prostate cancer.

PMID- 24124625
TI  - p53 as an intervention target for cancer and aging.
AB  - p53 is well known for suppressing tumors but could also affect other aging
      processes not associated with tumor suppression. As a transcription factor, p53
      responds to a variety of stresses to either induce apoptosis (cell death) or cell
      cycle arrest (cell preservation) to suppress tumor development. Yet, the effect
      p53 has on the non-cancer aspects of aging is complicated and not well
      understood. On one side, p53 could induce cellular senescence or apoptosis to
      suppress cancer but as an unintended consequence enhance the aging process
      especially if these responses diminish stem and progenitor cell populations. But
      on the flip side, p53 could reduce growth and growth-related stress to enable
      cell survival and ultimately delay the aging process. A better understanding of
      diverse functions of p53 is essential to elucidate its influences on the aging
      process and the possibility of targeting p53 or p53 transcriptional targets to
      treat cancer and ameliorate general aging. 

PMID- 24124628
TI  - The Fallout of the 2013 Budget Cuts on the NIH and the NIA and an Urgent Call for
      Action to Prevent Similar Cuts in the Future.

PMID- 24124629
TI  - Relationship of clinical and cognitive variables with brain morphometric
      abnormalities in Alzheimer's disease: a voxel based morphometric study using 3
      tesla MRI.
AB  - Alzheimer's disease (AD) is associated with widespread structural and functional
      brain alterations. The current study examined the gray matter (GM) voxel based
      morphometric (VBM) correlates of cognitive and clinical severity scores in
      patients with AD. The study included 34 patients with AD according to
      NINCDS/ADRDA AD criteria and 28 matched elderly controls. All subjects were
      clinically evaluated using Hindi Mental Status Examination (HMSE), Everyday
      Abilities Scale for India (EASI) and the Clinical Dementia Rating (CDR) scale.
      The structural Magnetic Resonance Imaging (MRI) data were acquired using a 3
      Tesla MRI scanner and VBM analysis was performed using VBM5.1 toolbox. The
      patients with AD had significantly lower GM volume, white matter volume and total
      brain volume as compared to controls. The HMSE scores were positively correlated
      (p=0.009) and EASI (p=0.04) & CDR (p=0.0004) were negatively correlated with the
      total GM volumes in patients with AD. The VBM analysis revealed diffuse GM
      atrophy in patients with AD. Frontal& temporal GM volumes were positively
      correlated with the HMSE scores. Thus the results of the study replicate the
      previous observations of generalized GM atrophy, in an Indian sample with AD. The
      cognitive decline, clinical dementia severity and impairment in activities of
      daily living were correlated whole brain GM and WM volumes as well as with
      specific brain regional atrophy in AD. However further studies with larger
      samples & with more detailed cognitive evaluation are required for confirmation &
      validation of the relationship between regional morphometric abnormalities and
      cognitive deficits in AD. 

PMID- 24124630
TI  - Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.
AB  - Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in
      the brain with aging contribute to the pathogenesis of AD. These changes can be
      found systematically and thus can be used as potential biomarkers. Erythrocytes
      (RBCs) are passive "reporter cells" that are not well studied in AD. In the
      present study, we analyzed an array of glycolytic and related enzymes and
      intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age
      matched controls (AC) and young adult controls (YC). AD is characterized by
      higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate
      mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed
      that glycolytic and related enzymes displayed significantly lower activities in
      AC. However, similar or significantly higher activities were observed in AD and
      NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were
      significantly decreased in AD and NA patients. The pattern of changes between
      groups in the above indices strongly correlates with each other. Collectively,
      our data suggested that AD and NA patients are associated with chronic
      disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role
      in physiological processes, which predispose elderly subjects to AD and NA. 

PMID- 24124631
TI  - Impact of resistance circuit training on neuromuscular, cardiorespiratory and
      body composition adaptations in the elderly.
AB  - Declines in maximal aerobic power and skeletal muscle force production with
      advancing age are examples of functional declines with aging, which can severely
      limit physical performance and independence, and are negatively correlated with
      all cause mortality. It is well known that both endurance exercise and resistance
      training can substantially improve physical fitness and health-related factors in
      older individuals. Circuit-based resistance training, where loads are lifted with
      minimal rest, may be a very effective strategy for increasing oxygen consumption,
      pulmonary ventilation, strength, and functional capacity while improving body
      composition. In addition, circuit training is a time-efficient exercise modality
      that can elicit demonstrable improvements in health and physical fitness. Hence,
      it seems reasonable to identify the most effective combination of intensity,
      volume, work to rest ratio, weekly frequency and exercise sequence to promote
      neuromuscular, cardiorespiratory and body composition adaptations in the elderly.
      Thus, the purpose of this review was to summarize and update knowledge about the
      effects of circuit weight training in older adults and elderly population, as a
      starting point for developing future interventions that maintain a higher quality
      of life in people throughout their lifetime. 

PMID- 24124632
TI  - Anorexia of aging and gut hormones.
AB  - We are expected to live longer than if we had been born 100 years ago however,
      the additional years are not necessarily spent in good health or free from
      disability. Body composition changes dramatically over the course of life. There
      is a gradual increase in body weight throughout adult life until the age of about
      60-65 years. In contrast, body weight appears to decrease with age after the age
      of 65-75 years, even in those demonstrating a previous healthy body weight. This
      age related decrease in body weight, often called unintentional weight loss or
      involuntary weight loss can be a significant problem for the elderly. This has
      been shown to be related to decline in appetite and food intake is common amongst
      the elderly and is often referred to the anorexia of aging. Underlying mechanisms
      regulate energy homeostasis and appetite may change as people age. In this
      review, peripheral factors regulating appetite have been summarized in regards to
      their age-dependent changes and role in the etiology of anorexia of aging.
      Understanding the alterations in the mechanisms regulating appetite and food
      intake in conjunction with aging may help inform strategies that promote healthy
      aging and promote health and wellbeing in the elderly years, with the end goal to
      add life to the years and not just years to our lives. 

PMID- 24124635
TI  - Primary spontaneous cerebrospinal fluid leaks located at the clivus.
AB  - Transclival meningoceles and primary spontaneous cerebrospinal fluid (CSF) leaks
      at the clivus are extremely rare lesions and only few of them have been reported
      in the literature. We report here six cases of transclival primary spontaneous
      CSF leaks through the clivus. A retrospective case study was performed. We
      reviewed six cases involving sinonasal CSF leaks located at the clivus treated
      between 1997 and 2009. Presenting symptoms, duration of symptoms, defect size,
      site of defect, surgical approach and technique of defect closure, intraoperative
      complications, postoperative complications, and recurrences are discussed. All
      CSF leaks were located in the upper central part of the clivus. two of six
      patients showed signs of increased intracranial pressure (ICP) including
      arachnoid pits and/or empty sella. For three patients a purely transnasal
      approach was used with multilayer reconstruction using a nonvascularized graft,
      and three patients underwent a transnasal transseptal approach with a multilayer
      reconstruction, with nasoseptal flap. No recurrences of CSF leaks at clivus or
      other sites were observed to date with a mean follow-up of 10.3 years (range, 3
      15 years). Spontaneous CSF rhinorrhea located at the clivus is an extremely rare
      condition. To date, only eight cases have been described. Here, we report the
      largest group of six consecutive cases. Irrespective of the used reconstruction
      technique in all cases a 100% closure rate was achieved. However, identification
      of increased ICP is an essential aspect and this condition should be treated
      either medically or surgically. 

PMID- 24124636
TI  - Total aplasia of the paranasal sinuses.
AB  - Although a variety of theories have been proposed about functions of the
      paranasal sinuses, not one is clear today. Nonetheless, paranasal sinus-related
      diseases are associated with a high rate of morbidities. Therefore, it is
      essential to identify the structure and pathophysiology of the paranasal sinuses.
      Computed tomography (CT) is a valuable tool displaying anatomic variations and
      diseases. Because paranasal sinus development is a complex and long-lasting
      process, there are great structural variations between individuals. Several
      degrees and combinations of aplasias and hypoplasias have been reported; however,
      there is only one case of total paranasal sinus aplasia in the literature. Here,
      we present the second case of total paranasal sinus aplasia. Paranasal sinus
      development, functions of the paranasal sinuses, and the role of CT were
      evaluated. 

PMID- 24124633
TI  - Carbonyl stress in aging process: role of vitamins and phytochemicals as redox
      regulators.
AB  - There is a growing scientific agreement that the cellular redox regulators such
      as antioxidants, particularly the natural polyphenolic forms, may help lower the
      incidence of some pathologies, including metabolic diseases like diabetes and
      diabesity, cardiovascular and neurodegenerative abnormalities, and certain
      cancers or even have anti-aging properties. The recent researches indicate that
      the degree of metabolic modulation and adaptation response of cells to reductants
      as well as oxidants establish their survival and homeostasis, which is linked
      with very critical balance in imbalances in cellular redox capacity and
      signaling, and that might be an answer the questions why some antioxidants or
      phytochemicals potentially could do more harm than good, or why some proteins
      lose their function by increase interactions with glyco- and lipo-oxidation
      mediates in the cells (carbonyl stress). Nonetheless, pursue of healthy aging has
      led the use of antioxidants as a means to disrupt age-associated physiological
      dysfunctions, dysregulated metabolic processes or prevention of many age-related
      diseases. Although it is still early to define their exact clinical benefits for
      treating age-related disease, a diet rich in polyphenolic or other forms of
      antioxidants does seem to offer hope in delaying the onset of age-related
      disorders. It is now clear that any deficiency in antioxidant vitamins,
      inadequate enzymatic antioxidant defenses can distinctive for many age-related
      disease, and protein carbonylation can used as an indicator of oxidative stress
      associated diseases and aging status. This review examines antioxidant compounds
      and plant polyphenols as redox regulators in health, disease and aging processes
      with hope that a better understanding of the many mechanisms involved with these
      distinct compounds, which may lead to better health and novel treatment
      approaches for age-related diseases. 

PMID- 24124634
TI  - Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features,
      Pathophysiology, Management and Therapeutic Trials.
AB  - Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in
      the 1870s, is an age-related disorder that leads to degeneration of motor
      neurons. The disease begins focally in the central nervous system and then
      spreads relentlessly. The clinical diagnosis, defined by progressive signs and
      symptoms of upper and lower motor neuron dysfunction, is confirmed by
      electromyography. Additional testing excludes other conditions. The disease is
      heterogeneous, but most patients die of respiratory muscle weakness less than 3
      years from symptom-onset. Like other age-related neurodegenerative diseases, ALS
      has genetic and environmental triggers. Of the five to 10% of cases that are
      inherited, mutations have been discovered for a high proportion. In addition to
      genetic factors, age, tobacco use, and athleticism may contribute to sporadic
      ALS, but important etiologies are unidentified for most patients. Complex
      pathophysiological processes, including mitochondrial dysfunction, aggregation of
      misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis,
      involve both motor neurons and surrounding glial cells. There is clinical and
      pathological overlap with other neurodegenerative diseases, particularly
      frontotemporal dementia. The mechanisms leading to disease propagation in the
      brain are a current focus of research. To date, one medication, riluzole,
      licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical
      trials have so far been unable to identify another neuroprotective agent.
      Researchers now aim to slow disease progression by targeting known
      pathophysiological pathways or genetic defects. Current approaches are directed
      at muscle proteins such as Nogo, energetic balance, cell replacement, and
      abnormal gene products resulting from mutations. Until better understanding of
      the causes and mechanisms underlying progression lead to more robust
      neuroprotective agents, symptomatic therapies can extend life and improve quality
      of life. Palliative care programs such as hospice give emotional and physical
      support to patients and families throughout much of the disease course. 

PMID- 24124637
TI  - Perceptual accuracy of upper airway compromise in children: Clinical relevance
      and future directions for research.
AB  - Approximately 80% of children with asthma have coexisting allergic rhinitis. The
      accurate recognition and assessment of asthma and rhinitis symptoms is an
      integral component of guideline-based treatment for both conditions. This article
      describes the development and preliminary evaluation of a novel paradigm for
      testing the accuracy of children's assessment of their upper airway (rhinitis)
      symptoms. This work is guided by our previous research showing the clinical
      efficacy of tools to evaluate children's perceptual accuracy of asthma symptoms
      and linking accurate asthma symptom perception to decreased asthma morbidity
      (Fritz G, et al., Ethnic differences in perception of lung function: A factor in
      pediatric asthma disparities? Am J Respir Crit Care Med 182:12-18, 2010; Klein
      RB, et al., The Asthma Risk Grid: Clinical interpretation of symptom perception,
      Allergy Asthma Proc 251-256, 2004). The pilot study tests a paradigm that allows
      for the examination of the correspondence of children's assessment of their upper
      airway functioning with actual values of upper airway flow through the use of a
      portable, handheld nasal peak flowmeter. Nine children with persistent asthma
      were evaluated over a 4-week period. The article describes the rhinitis
      perceptual accuracy paradigm and reviews the results of a pilot study, showing a
      large proportion of inaccurate rhinitis symptoms "guesses" by the sample of
      children with persistent asthma. Patterns of inaccuracy, rhinitis control, and
      asthma morbidity are also described. Directions for future work are reviewed. The
      development of clinical tools to evaluate children's accuracy of rhinitis
      symptoms are needed, given the central role of the self-assessment of symptoms in
      guideline-based care. Accurate perception of the severity of rhinitis symptoms
      may enhance rhinitis control, lessen the burden of asthma, and prevent
      unnecessary emergency use among this high-risk group of children. 

PMID- 24124638
TI  - Identification of pannexins in rat nasal mucosa.
AB  - Pannexins are a second family of gap-junction proteins in vertebrates, classified
      as pannexin-1, pannexin-2, and pannexin-3. Pannexin-1 is one of the candidates
      for channel-mediated ATP release into the extracellular space. In airway
      epithelia, ATP signaling modulates multiple cellular functions such as mucus/ion
      secretion and mucociliary clearance systems. However, the expression of pannexins
      in the upper airway has not been investigated. Nasal septal mucosae were
      collected from adult male Wistar rats aged 20-24 weeks. The expression of
      pannexin-1, pannexin-2, and pannexin-3 was examined by reverse transcription
      polymerase chain reaction (RT-PCR) and by whole-mount fluorescence
      immunohistochemistry. Transcripts for pannexin-1, pannexin-2, and pannexin-3 were
      detected in nasal septal mucosae of adult rats by RT-PCR. Distinct
      immunohistochemical fluorescence for pannexin-1 was observed in the epithelial
      layer, whereas there was no immunoreactivity for pannexin-2 or pannexin-3. This
      is the first article establishing the existence of pannexins (predominantly
      pannexin-1) in the upper airway, suggesting their possible participation in the
      physiological functions of ATP release and signaling in this tissue. 

PMID- 24124639
TI  - Validation of a grading system for lateral nasal wall insufficiency.
AB  - This study was designed to validate a grading scheme for lateral nasal wall
      insufficiency with interrater and intrarater reliability measures. Representative
      endoscopic videos depicting varied degrees of lateral nasal wall insufficiency
      were collated into a 30-clip video (15 clips in duplicate). This was rated by
      five reviewers for a total of 150 observations. Interrater and intrarater
      reliability were determined using Fleiss kappa and intraclass correlation
      coefficient (ICC) statistics, respectively. Good agreement was established
      between reviewers (interrater reliability), with a Fleiss kappa of 0.7733 (p <
      0.01). Analysis of intrarater variability with the ICC revealed a very strong
      agreement (ICC = 0.88; p < 0.01). The proposed grading system is shown to have
      good interrater and intrarater reliability. It provides a reliable instrument for
      assessing lateral wall insufficiency. 

PMID- 24124640
TI  - Immunopathology features of chronic rhinosinusitis in high-altitude dwelling
      Tibetans.
AB  - Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling
      patterns in different populations and environments. Tibetan ethnic groups live at
      high altitudes and in cold weather conditions. We sought to examine whether
      Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and
      mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps
      (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan
      controls. Tissue homogenates and serum samples were assayed for several T-helper
      (TH) cell cytokines and mediators using enzyme linked immunosorbent assay
      profiles were measured using quantity polymerase chain reaction. Several key
      inflammatory cells were examined for immunohistochemical markers. CRSwNPs were
      characterized by increased mediator promoting eosinophilic inflammation
      (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and
      slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and
      myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils.
      GATA-3 transcription factor was significantly increased and Foxp3 showed a
      tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were
      characterized by significantly high levels of transforming growth factor beta1,
      increased interferon gamma, and a significant enhancement of Foxp3 and T-beta
      compared with CRSwNPs. There were reduced numbers of inflammatory cells but
      increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs
      present a severe inflammatory reaction and show a TH2 milieu with apparently
      impaired regulatory T cells (Treg) function and increased inflammatory cells
      infiltration predominated by eosinophilic and mast cells. In contrast, TH1
      polarization with enhanced Treg function and increased levels of macrophages
      appear in CRSsNPs. 

PMID- 24124641
TI  - Characteristics of candidates for allergen immunotherapy.
AB  - Allergic rhinitis (AR) may be cured by allergen immunotherapy (AIT). However,
      patient characteristics for prescribing AIT are not well defined. This study
      aimed at evaluating the patient's profile to be a candidate for AIT in a cohort
      of patients suffering from AR, evaluated in 20 Italian Allergy or Ear, Nose, and
      Throat Centers. The study has been performed on 198 patients (98 men; mean age,
      26.8 years) with AR (assessed by Allergic Rhinitis and Its Impact on Asthma
      [ARIA] criteria). The kind and the number of prescribed allergen extracts, type
      of diagnosis, severity of symptoms, and patient's perception of symptoms and drug
      use were evaluated. Patients were subdivided in AIT-treated and without AIT (as
      controls) subgroups. Most of the patients (69.7%) had persistent AR with moderate
      severe symptoms. The mean number of sensitization was 3.4. ARIA classification
      and sensitization number did not affect AIT choice, but the type of allergen was
      relevant. AIT-treated patients had milder symptoms than controls if assessed by
      doctors, but AIT patients perceived more severe symptoms and larger drug use than
      controls. This study shows that the choice of AIT is based on patient's
      perception and type of allergen, but number of sensitizations, symptom severity
      assessed by doctors, and ARIA classification are not relevant factors. The key
      message might be that it is always relevant to pay attention to the complaints
      referred by the patient. 

PMID- 24124642
TI  - Unilateral transnasal endoscopic approach to frontal sinuses: Draf IIc.
AB  - For chronic sinusitis surgery, the Draf III approach provides a common median
      drainage pathway for bilateral frontal sinuses from orbit to orbit. The Draf IIb
      provides unilateral drainage from orbit to septum. In several cases, inclusion of
      the nasal and frontal sinus septum in a Draf IIb was advantageous without
      extension to the opposite frontal recess. The proposed nomenclature is Draf IIc.
      This study was designed to (1) develop a surgical option for chronic frontal
      sinusitis where access to one frontal recess is limited or unnecessary and (2)
      minimize unnecessary surgical manipulation of uninvolved areas. Revision
      endoscopic frontal sinus surgery was performed on two patients with persistent
      frontal sinus opacification. Surgery crossed midline including one frontal recess
      with resection of the superior nasal septum. The surgical result was assessed on
      endoscopy and computed tomography (CT). The postoperative course was unremarkable
      with relief of frontal pressure. Postoperative CT scan showed well-aerated
      frontal sinuses with a widely patent common drainage pathway. Postoperative nasal
      endoscopy revealed normal mucosa with no exposed bone or edema. The Draf IIc
      extends the Draf IIb across the midline, without including the opposite frontal
      recess. This can be accomplished most easily using an interfrontal sinus septal
      cell or an eccentric interfrontal sinus septum. The Draf IIc is a surgical option
      in cases of chronic or recalcitrant frontal sinus diseases, including unilateral
      or bilateral obstruction, where access to the ipsilateral frontal recess is
      limited or favorable anatomy allows drainage with reduced manipulation of an
      uninvolved side. 

PMID- 24124643
TI  - Sinonasal involvement in systemic vasculitides and cocaine-induced midline
      destructive lesions: Diagnostic controversies.
AB  - Multiple systemic diseases produce various clinical manifestations in the
      sinonasal area. They usually appear as difficult-to-diagnose disease processes
      with slow, atypical clinical courses. The aim of this study was to evaluate the
      sinonasal manifestations of systemic vasculitides, highlighting key points for
      diagnosis and differential diagnosis with other pathological entities, especially
      cocaine-induced midline destructive lesions (CIMDL). A retrospective study was
      performed of 10 patients treated in our hospital during the last 5 years with an
      initial diagnosis of systemic vasculitides with sinonasal involvement: eight
      patients with granulomatosis with polyangiitis (GPA; new nomenclature for Wegener
      granulomatosis) and two patients with Churg-Strauss syndrome (CSS). The study
      variables were clinical presentation, nasal endoscopy results, maxillofacial scan
      results, nasal biopsy results, erythrocyte sedimentation rate, and autoimmune
      antibody levels. The definitive diagnosis was GPA in six (60%) patients, CSS in
      two (20%) patients, and CIMDL in two (20%) patients. Nasal symptoms were similar
      in all patients, but nasal polyps were present in only one patient with CSS.
      Systemic manifestations were absent in patients with CIMDL. Likewise, peripheral
      eosinophilia was observed only in the two patients with CSS. Specific positive
      biopsy specimens were obtained in six patients (all six patients with GPA, one
      with CSS, and one with CIMDL). Antineutrophil cytoplasmic antibodies (ANCA) were
      positive in all patients with GPA (proteinase 3 antigen in five patients and
      myeloperoxidase in one patient), and perinuclear ANCA was positive in one patient
      with CIMDL; however, this patient showed an undefined pattern. Finally, the
      response to treatment was adequate in all patients excluding those with CIMDL.
      GPA and CIMDL syndromes pose a difficult differential diagnosis because they have
      common clinical, serological, and histological presentations. Negative
      histological results do not exclude the diagnosis of sinonasal vasculitides. The
      absence of systemic manifestations and the lack of response to treatment will
      lead to the confirmation of CIMDL syndrome in a cocaine user. Otolaryngologists
      play an important role in the early and differential diagnosis of these diseases.

PMID- 24124644
TI  - Statistical Analysis of Patient-Specific Pathway Activities via Mixed Models.
AB  - In the study of complex diseases, a major challenge is disease heterogeneity,
      where the dysregulation of different pathways often lead to similar disease
      phenotypes. As a result, a given pathway could be differentially expressed with
      respect to controls for some patients, but not for others. Therefore, to develop
      successful personalized treatment regime, in addition to identifying disease
      relevant pathways for the entire patient group, it's also important to test if a
      particular pathway is dysregulated for an individual patient. To this end, we
      compare pathway gene expression profile for a particular individual in the
      patient group to the "norm" (or standard) established by a group of control
      patients. We studied statistical analysis of patient-specific pathway activities
      under the mixed models framework. Using gene expression dataset with realistic
      correlation patterns, we showed the proposed hypothesis testing procedure had
      false positive rate (type I error) as expected. In addition, we illustrated the
      proposed methodology using a Type 2 Diabetes dataset. Our results showed a
      previously diabetes associated pathway was only differentially expressed
      (relative to the control group) in less than 30% of the diabetes patients, which
      provided an explanation for the moderate group level statistical significance
      seen in a previous study. This result also suggested targeting this particular
      pathway would likely be beneficial for only 30% of the patients. In addition to
      the case-control study we have illustrated, this model can be easily extended to
      handle more complex designs with additional covariates and multiple sources of
      variations. Moreover, the proposed model operates within a well-established
      statistical framework and can be implemented in common statistical packages.

PMID- 24124645
TI  - Effects of historical and modern mining on mercury deposition in southeastern
      Peru.
AB  - Both modern anthropogenic emissions of mercury (Hg), primarily from artisanal and
      small-scale gold mining (ASGM), and preindustrial anthropogenic emissions from
      mining are thought to have a large impact on present-day atmospheric Hg
      deposition. We study the spatial distribution of Hg and its depositional history
      over the past ~400 years in sediment cores from lakes located regionally proximal
      (~90-150 km) to the largest ASGM in Peru and distal (>400 km) to major
      preindustrial mining centers. Total Hg concentrations in surface sediments from
      fourteen lakes are typical of remote regions (10-115 ng g(-1)). Hg fluxes in
      cores from four lakes demonstrate preindustrial Hg deposition in southeastern
      Peru was spatially variable and at least an order of magnitude lower than
      previously reported fluxes in lakes located closer to mining centers. Average
      modern (A.D. 2000-2011) Hg fluxes in these cores are 3.4-6.9 MUg m(-2) a(-1),
      compared to average preindustrial (A.D. 1800-1850) fluxes of 0.8-2.5 MUg m(-2) a(
      1). Modern Hg fluxes determined from the four lakes are on average 3.3 (+/-1.5)
      times greater than their preindustrial fluxes, similar to those determined in
      other remote lakes around the world. This agreement suggests that Hg emissions
      from ASGM are likely not significantly deposited in nearby down-wind regions. 

PMID- 24124646
TI  - Arrayed profiling of multiple glycans on whole living cell surfaces.
AB  - An array-based method for profiling and quantification of multiple glycans on
      whole living cell surfaces was developed through combining DNA encoding
      technology with DNA microarray. Using four kinds of lectins as the model to
      recognize four types of cell surface glycans, the specific barcode-lectin probes
      that contained the endonuclease cutting site were designed. The barcode-lectin
      probes had the DNA sequences complementary to four sequences immobilized on a DNA
      microarray, respectively. After the living cells were incubated with the mixture
      of four barcode-lectin probes, these probes could bind to cell surface through
      the specific interaction between the lectins and corresponding glycans. Thus, the
      glycans and their amounts could be profiled by releasing the barcodes from cell
      surface with endonuclease cleaving, binding the barcodes to DNA microarray with
      specific hybridization, and then producing the amplified fluorescence signal with
      hybridization chain reaction (HCR). The HCR was performed with two kinds of Cy5
      labeled hairpins. The average amount of mannose, N-acetylgalactosamine, N
      acetylglucosamine, and N-acetylneuraminic acid on BGC cell was obtained to be 6.8
      * 10(7), 3.8 * 10(7), 2.1 * 10(8), and 1.1 * 10(7) moieties per cell,
      respectively. The proposed method possessed whole cell surface accessibility,
      powerful distinguishing capability, fast recognition kinetics, easy
      miniaturization, and high throughput without need of cell pretreatment or
      labeling. It could become a powerful tool for elucidation of the complex glycan
      related biological processes. 

PMID- 24124647
TI  - Iron oxychloride (FeOCl): an efficient Fenton-like catalyst for producing
      hydroxyl radicals in degradation of organic contaminants.
AB  - An iron oxychloride (FeOCl) catalyst was developed for oxidative degradation of
      persistent organic compounds in aqueous solutions. Exceptionally high activity
      for the production of hydroxyl radical (OH.) by H2O2 decomposition was achieved,
      being 2-4 orders of magnitudes greater than that over other Fe-based
      heterogeneous catalysts. The relationship of catalyst structure and performance
      has been established by using multitechniques, such as XRD, HRTEM, and EPR. The
      unique structural configuration of iron atoms and the reducible electronic
      properties of FeOCl are responsible for the excellent activity. This study paves
      the way toward the rational design of relevant catalysts for applications, such
      as wastewater treatment, soil remediation, and other emerging environmental
      problems. 

PMID- 24124648
TI  - Alternative fusion protein strategies to express recalcitrant QconCAT proteins
      for quantitative proteomics of human drug metabolizing enzymes and transporters.
AB  - QconCAT is a tool for quantitative proteomics, consisting of an artificial
      protein, expressed from an artificial gene, made up of a concatenated string of
      proteotypic peptides selected from the proteins under study. Isotopically labeled
      QconCAT (usually containing (13)C6-arginine and (13)C6-lysine) provides a
      standard for each proteotypic peptide included in its sequence. In practice, some
      QconCAT proteins fail to express at sufficient levels for the purpose of
      quantitative analysis. Two complementary methods are presented to express
      recalcitrant QconCAT proteins intended to quantify human hepatic enzymes and
      transporters. 

PMID- 24124649
TI  - In vivo determination of epidermal thickness using high-definition optical
      coherence tomography.

PMID- 24124650
TI  - Hydrocephalus with panventricular enlargement as the primary manifestation of
      neurosarcoidosis: a case report.
AB  - INTRODUCTION: Hydrocephalus is very uncommon in neurosarcoidosis. To date, there
      have been only five reported cases of hydrocephalus occurring as the first
      manifestation of neurosarcoidosis. Such a presentation in a previously healthy
      patient is challenging to diagnose. CASE PRESENTATION: A 31-year-old Japanese man
      who had no relevant past history other than sinusitis was admitted to our
      institution complaining of low-grade fever and mild headache. He was alert and
      neurologically intact. No respiratory symptoms were observed. Laboratory
      examination revealed mild elevation of erythrocyte sedimentation rate and serum
      CD4/CD8 ratio. Serum angiotensin-converting enzyme level was in the normal range.
      His cerebrospinal fluid showed mild pleocytosis and increased protein level. A
      chest X-ray revealed bihilar lymphadenopathy with normal lung parenchyma.
      Computed tomography of his head showed remarkable hydrocephalus with dilatation
      of all ventricles, particularly the fourth. Gadolinium-enhanced magnetic
      resonance imaging demonstrated leptomeningeal millet seed-like enhancement and
      multiple small enhancing lesions along the Virchow-Robin spaces. These findings
      strongly suggested a chronic inflammatory disease such as neurosarcoidosis. To
      treat the hydrocephalus, a ventriculoperitoneal shunt was inserted. The
      postoperative course was satisfactory. After surgery, nasal and skin biopsies
      were performed and pathological analysis revealed non-caseating granulomas
      consistent with sarcoidosis. The findings of gallium scintigraphy also supported
      the diagnosis of sarcoidosis. We obtained the definitive diagnosis of sarcoidosis
      3 weeks after admission from the pathological findings by the nasal and skin
      biopsies, and corticosteroid therapy was started after that. CONCLUSION: We
      present a rare case of neurosarcoidosis manifesting as acute hydrocephalus with
      dilatation of all ventricles, particularly the fourth. As hydrocephalus due to
      neurosarcoidosis has high morbidity and mortality, early diagnosis and proper
      treatment are particularly important.

PMID- 24124651
TI  - Circulating levels of soluble receptor for advanced glycation end product are
      inversely associated with vascular calcification in patients on haemodialysis
      independent of S100A12 (EN-RAGE) levels.
AB  - AIM: The receptor for advanced glycation end products (RAGE) has emerged as a
      central regulator of vascular inflammation and atherosclerosis. Soluble RAGE
      (sRAGE) has an anti-inflammatory effect by quenching ligands for RAGE. On the
      other hand, extracellular RAGE-binding protein S100A12 (EN-RAGE) shows a pro
      inflammatory effect in a way, but may play pleiotropic roles related to
      inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in
      haemodialysis (HD) patients and evaluated their relationship with vascular
      calcification. METHODS: We performed a cross-sectional study with 199 HD
      patients. Plain X-ray images of the lateral lumbar spine from all subjects were
      studied to calculate semiquantitative vascular calcification scores (VCS), as
      described by Kauppila. Commercially available enzyme linked immunosorbent assay
      (ELISA) kits were used to quantify the serum concentration of sRAGE and S100A12.
      RESULTS: The patients were 57.1 +/- 13.7 years of age; 54.3% were male, 49.2%
      were diabetic, and 36.2% had a history of cardiovascular disease. In a univariate
      analysis, serum sRAGE was negatively associated with VCS (log sRAGE, r=-0.208,
      P=0.003), whereas S100A12 showed a positive tendency (log S100A12, r=0.235,
      P=0.085). Even after adjustments for confounding risk factors, sRAGE was
      independently associated with VCS (beta=-1.679, P=0.002). CONCLUSION: This study
      demonstrated that the circulating sRAGE level was inversely associated with VCS
      in HD patients independent of the S100A12 level and the severity of systemic
      inflammation.

PMID- 24124653
TI  - Prediction of residual feed intake for first-lactation dairy cows using
      orthogonal polynomial random regression.
AB  - Residual Feed Intake (RFI) is a measure of energy efficiency. Developing an
      appropriate model to predict expected energy intake while accounting for
      multifunctional energy requirements of metabolic body weight (MBW), empty body
      weight (EBW), milk production energy requirements (MPER), and their nonlinear
      lactation profiles, is the key to successful prediction of RFI in dairy cattle.
      Individual daily actual energy intake and monthly body weight of 281 first
      lactation dairy cows from 1 to 305 d in milk were recorded at the Dairy Research
      and Technology Centre of the University of Alberta (Edmonton, AB, Canada);
      individual monthly milk yield and compositions were obtained from the Dairy Herd
      Improvement Program. Combinations of different orders (1-5) of fixed (F) and
      random (R) factors were fitted using Legendre polynomial regression to model the
      nonlinear lactation profiles of MBW, EBW, and MPER over 301 d. The F5R3, F5R3,
      and F5R2 (subscripts indicate the order fitted) models were selected, based on
      the combination of the log-likelihood ratio test and the Bayesian information
      criterion, as the best prediction equations for MBW, EBW, and MPER, respectively.
      The selected models were used to predict daily individual values for these
      traits. To consider the body reserve changes, the differences of predicted EBW
      between 2 consecutive days were considered as the EBW change between these days.
      The smoothed total 301-d actual energy intake was then linearly regressed on the
      total 301-d predicted traits of MBW, EBW change, and MPER to obtain the first
      lactation RFI (coefficient of determination=0.68). The mean of predicted daily
      average lactation RFI was 0 and ranged from -6.58 to 8.64 Mcal of NE(L)/d. Fifty
      one percent of the animals had an RFI value below the mean (efficient) and 49% of
      them had an RFI value above the mean (inefficient). These results indicate that
      the first-lactation RFI can be predicted from its component traits with a
      reasonable coefficient of determination. The predicted RFI could be used in the
      dairy breeding program to increase profitability by selecting animals that are
      genetically superior in energy efficiency based on RFI, or through routinely
      measured traits, which are genetically correlated with RFI.

PMID- 24124652
TI  - Acute liver injury induces nucleocytoplasmic redistribution of hepatic methionine
      metabolism enzymes.
AB  - AIMS: The discovery of methionine metabolism enzymes in the cell nucleus,
      together with their association with key nuclear processes, suggested a putative
      relationship between alterations in their subcellular distribution and disease.
      RESULTS: Using the rat model of d-galactosamine intoxication, severe changes in
      hepatic steady-state mRNA levels were found; the largest decreases corresponded
      to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic
      protein levels, activities, and metabolite concentrations suffered more moderate
      changes following a similar trend. Interestingly, galactosamine treatment induced
      hepatic nuclear accumulation of methionine adenosyltransferase (MAT) alpha1 and S
      adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact,
      galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen
      (APAP) intoxication mimicked most galactosamine effects on hepatic MATalpha1,
      including accumulation of nuclear tetramers. H35 cells that overexpress tagged
      MATalpha1 reproduced the subcellular distribution observed in liver, and the
      changes induced by galactosamine and APAP that were also observed upon
      glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of
      tagged-MATalpha1 induced by these agents correlated with decreased glutathione
      reduced form/glutathione oxidized form ratios and was prevented by N
      acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in
      epigenetic modifications associated with tagged-MATalpha1 nuclear accumulation
      were only prevented by NAC in galactosamine-treated cells. INNOVATION:
      Cytoplasmic and nuclear changes in proteins that regulate the methylation index
      follow opposite trends in acute liver injury, their nuclear accumulation showing
      potential as disease marker. CONCLUSION: Altogether these results demonstrate
      galactosamine- and APAP-induced nuclear accumulation of methionine metabolism
      enzymes as active oligomers and unveil the implication of redox-dependent
      mechanisms in the control of MATalpha1 subcellular distribution.

PMID- 24124654
TI  - Comparison between sire-maternal grandsire and animal models for genetic
      evaluation of longevity in a dairy cattle population with small herds.
AB  - Survival analysis techniques for sire-maternal grandsire (MGS) and animal models
      were used to test the genetic evaluation of longevity in a Slovenian Brown cattle
      population characterized by small herds. Three genetic models were compared: a
      sire-MGS model for bulls and an approximate animal model based on estimated
      breeding values (EBV) from the sire-MGS model for cows, an animal model, and an
      animal model based on the estimated variance components from the sire-MGS model.
      In addition, modeling the contemporary group effect was defined as either a herd
      or a herd-year (HY) effect. With various restrictions on the minimum HY group
      size (from 1 to 10 cows per HY), changes in estimates of variance components, and
      consequently also in EBV, were observed for the sire-MGS and animal models.
      Variance of contemporary group effects decreased when an HY effect was fitted
      instead of a herd effect. In the case of a sire-MGS model, estimates of additive
      genetic variance were mostly robust to changes in minimum HY group size or
      fitting herd or HY effect, whereas they increased in the animal model when HY
      instead of herd effects was fitted, possibly revealing some confounding between
      cow EBV and contemporary group effect. Estimated heritabilities from sire-MGS
      models were between 0.091 and 0.119 and were mainly influenced by the restriction
      on the HY group size. Estimated heritabilities from animal models were higher:
      between 0.125 and 0.160 when herd effect was fitted and between 0.171 and 0.210
      when HY effect was fitted. Rank correlations between the animal model and the
      approximate animal model based on EBV from the sire-MGS model were high: 0.94 for
      cows and 0.93 for sires when a herd effect was fitted and 0.90 for cows and 0.93
      for sires when an HY effect was fitted. Validation performed on the independent
      validation data set revealed that the correlation between sire EBV and daughter
      survival were slightly higher with the approximate animal model based on EBV from
      the sire-MGS model compared with the animal model. The correlations between the
      sire EBV and daughter survival were higher when the model included an HY effect
      instead of a herd effect. To avoid confounding and reduce computational
      requirements, it is suggested that the approximate animal model based on EBV from
      the sire-MGS model and HY as a contemporary group effect is an interesting
      compromise for practical applications of genetic evaluation of longevity in
      cattle populations. 

PMID- 24124655
TI  - Sugared water consumption by adult offspring of mothers fed a protein-restricted
      diet during pregnancy results in increased offspring adiposity: the second hit
      effect.
AB  - Poor maternal nutrition predisposes offspring to metabolic disease. This
      predisposition is modified by various postnatal factors. We hypothesised that
      coupled to the initial effects of developmental programming due to a maternal low
      protein diet, a second hit resulting from increased offspring postnatal sugar
      consumption would lead to additional changes in metabolism and adipose tissue
      function. The objective of the present study was to determine the effects of
      sugared water consumption (5% sucrose in the drinking-water) on adult offspring
      adiposity as a 'second hit' following exposure to maternal protein restriction
      during pregnancy. We studied four offspring groups: (1) offspring of mothers fed
      the control diet (C); (2) offspring of mothers fed the restricted protein diet
      (R); (3) offspring of control mothers that drank sugared water (C-S); (4)
      offspring of restricted mothers that drank sugared water (R-S). Maternal diet in
      pregnancy was considered the first factor and sugared water consumption as the
      second factor - the second hit. Body weight and total energy consumption, before
      and after sugared water consumption, were similar in all the groups. Sugared
      water consumption increased TAG, insulin and cholesterol concentrations in both
      the sexes of the C-S and R-S offspring. Sugared water consumption increased
      leptin concentrations in the R-S females and males but not in the R offspring.
      There was also an interaction between sugared water and maternal diet in males.
      Sugared water consumption increased adipocyte size and adiposity index in both
      females and males, but the interaction with maternal diet was observed only in
      females. Adiposity index and plasma leptin concentrations were positively
      correlated in both the sexes. The present study shows that a second hit during
      adulthood can amplify the effects of higher adiposity arising due to poor
      maternal pregnancy diet in an offspring sex dependent fashion.

PMID- 24124656
TI  - Clinical relevance of routinely measured vital signs in hospitalized patients: a
      systematic review.
AB  - BACKGROUND: Conflicting evidence exists on the effectiveness of routinely
      measured vital signs on the early detection of increased probability of adverse
      events. PURPOSE: To assess the clinical relevance of routinely measured vital
      signs in medically and surgically hospitalized patients through a systematic
      review. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled
      Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature, and
      Meta-analysen van diagnostisch onderzoek (in Dutch; MEDION) were searched to
      January 2013. STUDY SELECTION: Prospective studies evaluating routine vital sign
      measurements of hospitalized patients, in relation to mortality, septic or
      circulatory shock, intensive care unit admission, bleeding, reoperation, or
      infection. DATA EXTRACTION: Two reviewers independently assessed potential bias
      and extracted data to calculate likelihood ratios (LRs) and predictive values.
      DATA SYNTHESIS: Fifteen studies were performed in medical (n = 7), surgical (n =
      4), or combined patient populations (n = 4; totaling 42,565 participants). Only
      three studies were relatively free from potential bias. For temperature, the
      positive LR (LR+) ranged from 0 to 9.88 (median 1.78; n = 9 studies); heart rate
      0.82 to 6.79 (median 1.51; n = 5 studies); blood pressure 0.72 to 4.7 (median
      2.97; n = 4 studies); oxygen saturation 0.65 to 6.35 (median 1.74; n = 2
      studies); and respiratory rate 1.27 to 1.89 (n = 3 studies). Overall, three
      studies reported area under the Receiver Operator Characteristic (ROC) curve
      (AUC) data, ranging from 0.59 to 0.76. Two studies reported on combined vital
      signs, in which one study found an LR+ of 47.0, but in the other the AUC was not
      influenced. CONCLUSIONS: Some discriminative LR+ were found, suggesting the
      clinical relevance of routine vital sign measurements. However, the subject is
      poorly studied, and many studies have methodological flaws. Further rigorous
      research is needed specifically intended to investigate the clinical relevance of
      routinely measured vital signs. CLINICAL RELEVANCE: The results of this research
      are important for clinical nurses to underpin daily routine practices and
      clinical decision making.

PMID- 24124657
TI  - Diabetes is not associated with an increased peri-operative mortality or non
      infectious morbidity following lower extremity arterial reconstruction.
AB  - BACKGROUND: The aim of this study was to determine if, at a national level,
      diabetes mellitus is associated with worse perioperative outcomes after open
      lower extremity arterial reconstruction. METHODS: Using Current Procedural
      Terminology codes, the National Surgical Quality Improvement Program database was
      queried to identify diabetic and nondiabetic patients who underwent open lower
      extremity arterial reconstruction from January 1, 2005, to December 31, 2007.
      These 2 groups were then compared using bivariate and multivariate analyses.
      RESULTS: There was no difference in mortality between the 2 groups (3.3% in
      diabetics and 3.5% in nondiabetics, P = .618). On multivariate analysis, there
      was no difference in the incidence of cardiac, pulmonary, or renal complications
      between the 2 groups. Diabetics, though, were more likely to develop infectious
      complications postoperatively. CONCLUSIONS: After lower extremity arterial
      reconstruction, diabetes is not associated with an increased risk for mortality
      or an increased rate of major postoperative complications. Diabetics, however,
      have an increased rate of certain perioperative infections.

PMID- 24124658
TI  - The general surgery workforce shortage is worse when assessed at county level.
AB  - BACKGROUND: Multiple studies have documented a significant decrease in the
      general surgery workforce in the United States, both rural and urban, for the
      past 3 decades. This 11-year study evaluates the Texas general surgery workforce
      at both the state and local level in 2002 and 2012. METHODS: Data were obtained
      from the Texas Medical Board, the United States Census Bureau/Texas State Library
      and Archives Commission, and the Texas Department of State Health Services for
      2002 and 2012. A benchmark target of 7 general surgeons per 100,000 population
      was used. RESULTS: During the study period, the Texas population increased 21%,
      and actively practicing physicians increased 44%. All surgical specialists
      increased by 26%. General surgeons increased 4%; however, the number of general
      surgeons per 100,000 population decreased 14% (from 6.7 to 5.8/10(5)). Using the
      total Texas population for 2012, an additional 329 general surgeons are needed by
      benchmark standards. However, when analyzed by individual county population, 449
      additional general surgeons are needed in the individual counties. These effects
      were greater in the nonmetropolitan areas of Texas where per capita general
      surgeons decreased by 21%. CONCLUSIONS: The absolute increase in Texas general
      surgeons over the past decade has not kept pace with an increase in the Texas
      population. The general surgery workforce deficit based on the Texas state
      population underestimates the local workforce shortage, particularly in the
      nonmetropolitan areas of Texas.

PMID- 24124659
TI  - Current management of acute malignant large bowel obstruction: a systematic
      review.
AB  - BACKGROUND: The management of colonic obstruction has changed in recent years. In
      distal obstruction, optimal treatment remains controversial, particularly after
      the appearance and use of colonic endoluminal stents. The purpose of this study
      was to review the current treatment of acute malignant large bowel obstruction
      according to the level of evidence of the available literature. METHODS: A
      systematic search was conducted in PubMed, MEDLINE, Embase, and Google Scholar
      for articles published through January 2013 to identify studies of large bowel
      obstruction and colorectal cancer. Included studies were randomized and
      nonrandomized controlled trials, reviews, systematic reviews, and meta-analysis.
      RESULTS: After a literature search of 1,768 titles and abstracts, 218 were
      selected for full-text assessment; 59 studies were ultimately included. Twenty
      five studies of the diagnosis and treatment of obstruction and 34 studies of the
      use of stents were assessed. CONCLUSIONS: In view of the various alternatives and
      the lack of high-grade evidence, the treatment of distal colonic obstruction
      should be individually tailored to each patient.

PMID- 24124660
TI  - Preoperative imaging for early-stage cutaneous melanoma: predictors, usage, and
      utility at a single institution.
AB  - BACKGROUND: Preoperative imaging for early-stage cutaneous melanoma is not
      recommended by current guidelines. Our goal was to investigate our institutional
      usage and utility. METHODS: Patients with clinically node-negative cutaneous
      melanoma undergoing surgery with sentinel lymph node biopsy were identified
      retrospectively. Any melanoma-related imaging after diagnosis and before surgery
      was considered a staging study. RESULTS: Five hundred fifteen studies were
      performed in 409 of 546 (75%) patients. Chest x-rays was performed in 70% and
      advanced imaging in 14% (computed tomography imaging, magnetic resonance imaging,
      ultrasound, and positron-emission computed tomography imaging). No metastatic
      lesions were identified. A Breslow thickness greater than 4 mm (odds ratio = 6.46
      vs <1 mm; 95% confidence interval, 2.07 to 20.15) and male sex (odds ratio = 2.62
      vs female; 95% confidence interval, 1.26 to 5.46) were associated with an
      increased likelihood of advanced imaging. CONCLUSIONS: Preoperative imaging was
      performed in the majority of patients with node-negative melanoma, with 14%
      undergoing advanced studies. No metastatic lesions were identified, confirming
      the limited utility in this setting.

PMID- 24124661
TI  - Evaluation of the prognostic value of the metastatic lymph node ratio for gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to investigate the prognostic value of
      metastatic lymph node (LN) ratio (LNR) compared with pathologic node (pN)
      category. METHODS: Three hundred ninety-nine patients with gastric cancer with R0
      resection were reviewed. LNR, pN, and the number of retrieved LNs were evaluated
      in node-positive groups with >=15 or <15 LNs resected and a node-negative group,
      respectively, by univariate and multivariate analyses. Associations of pN and LNR
      with the number of retrieved LNs were determined using Spearman's rank
      correlation test. RESULTS: LNR and pN were correlated with overall survival. For
      the node-positive group with >=15 LNs retrieved, pN and LNR were independent
      prognostic factors, with the hazard ratio higher for LNR; neither was correlated
      with the number of retrieved LNs. For the group with <15 LNs retrieved, LNR but
      not pN was an independent prognostic factor, with LNR uncorrelated with the
      number of LNs retrieved. For the node-negative group, the number of LNs retrieved
      retained an independent prognostic factor. CONCLUSIONS: LNR is an independent
      prognostic factor in node-positive patients with gastric cancer with R0
      resection, and it is uninfluenced by the number of LNs retrieved. It may be
      superior to pN.

PMID- 24124662
TI  - Outcomes and prognostic factors in superficial spreading melanoma.
AB  - BACKGROUND: Prognostic factors and risk factors for positive sentinel lymph node
      (SLN) biopsy results are important to identify in superficial spreading melanoma
      (SSM). METHODS: A single-center database and a prospective clinical trial
      database were reviewed for all patients with diagnoses of SSM. Logistic
      regression, Kaplan-Meier survival analysis, and univariate and multivariate Cox
      models were used. RESULTS: A total of 1,643 patients with SSM were identified.
      Independent risk factors for positive SLN biopsy results were Breslow thickness
      (BT) >=2.0 mm, age <60 years, and presence of ulceration. BT >=2.0 mm,
      ulceration, lymphovascular invasion, and positive SLN and positive non-SLN biopsy
      results were independent risk factors for worse disease-free survival.
      Independent overall survival risk factors included BT >=2.0 mm, age >=60 years,
      ulceration, nonextremity tumor location, lymphovascular invasion, and positive
      SLN biopsy results. CONCLUSIONS: BT, ulceration, lymphovascular invasion, and SLN
      and non-SLN status are important risk factors for SSM.

PMID- 24124663
TI  - Involving traditional birth attendants in emergency obstetric care in Tanzania:
      policy implications of a study of their knowledge and practices in Kigoma Rural
      District.
AB  - INTRODUCTION: Access to quality maternal health services mainly depends on
      existing policies, regulations, skills, knowledge, perceptions, and economic
      power and motivation of service givers and target users. Critics question policy
      recommending involvement of traditional birth attendants (TBAs) in emergency
      obstetric care (EmoC) services in developing countries. OBJECTIVES: This paper
      reports about knowledge and practices of TBAs on EmoC in Kigoma Rural District,
      Tanzania and discusses policy implications on involving TBAs in maternal health
      services. METHODS: 157 TBAs were identified from several villages in 2005,
      interviewed and observed on their knowledge and practice in relation to EmoC.
      Quantitative and qualitative techniques were used for data collection and
      analysis depending on the nature of the information required. FINDINGS: Among all
      157 TBAs approached, 57.3% were aged 50+ years while 50% had no formal education.
      Assisting mothers to deliver without taking their full pregnancy history was
      confessed by 11% of all respondents. Having been attending pregnant women with
      complications was experienced by 71.2% of all respondents. Only 58% expressed
      adequate knowledge on symptoms and signs of pregnancy complications. Lack of
      knowledge on possible risk of HIV infections while assisting childbirth without
      taking protective gears was claimed by 5.7% of the respondents. Sharing the same
      pair of gloves between successful deliveries was reported to be a common practice
      by 21.1% of the respondents. Use of unsafe delivery materials including local
      herbs and pieces of cloth for protecting themselves against HIV infections was
      reported as being commonly practiced among 27.6% of the respondents. Vaginal
      examination before and during delivery was done by only a few respondents.
      CONCLUSION: TBAs in Tanzania are still consulted by people living in underserved
      areas. Unfortunately, TBAs' inadequate knowledge on EmOC issues seems to have
      contributed to the rising concerns about their competence to deliver the
      recommended maternal services. Thus, the authorities seeming to recognize and
      promote TBAs should provide support to TBAs in relation to necessary training and
      giving them essential working facilities, routine supportive supervision and
      rewarding those seeming to comply with the standard guidelines for delivering
      EmoC services.

PMID- 24124664
TI  - A Landau-Squire nanojet.
AB  - Fluid jets are found in nature at all length scales from microscopic to
      cosmological. Here we report on an electroosmotically driven jet from a single
      glass nanopore about 75 nm in radius with a maximum flow rate ~15 pL/s. A novel
      anemometry technique allows us to map out the vorticity and velocity fields that
      show excellent agreement with the classical Landau-Squire solution of the Navier
      Stokes equations for a point jet. We observe a phenomenon that we call flow
      rectification: an asymmetry in the flow rate with respect to voltage reversal.
      Such a nanojet could potentially find applications in micromanipulation,
      nanopatterning, and as a diode in microfluidic circuits.

PMID- 24124665
TI  - Tilt angles and positive response of head-up tilt test in children with
      orthostatic intolerance.
AB  - This study aimed at examining three tilt angle-based positive responses and the
      time to positive response in a head-up tilt test for children with orthostatic
      intolerance, and the psychological fear experienced at the three angles during
      head-up tilt test. A total of 174 children, including 76 boys and 98 girls, aged
      from 4 to 18 years old (mean 11.3+/-2.8 years old), with unexplained syncope,
      were randomly divided into three groups, to undergo head-up tilt test at the
      angles of 60 degrees , 70 degrees  and 80 degrees , respectively. The diagnostic
      rates and times were analysed, and Wong-Baker face pain rating scale was used to
      access the children's psychological fear. There were no significant differences
      in diagnostic rates of postural orthostatic tachycardia syndrome and vasovagal
      syncope at different tilt angles during the head-up tilt test (p>0.05). There was
      a significant difference, however, in the psychological fear at different tilt
      angles utilising the Kruskal-Wallis test (chi2=36.398, p<0.01). It was mildest at
      tilt angle 60 degrees  utilising the Kolmogorov-Smirnov test (p<0.01). A positive
      rank correlation was found between the psychological fear and the degree of tilt
      angle (r(s)=0.445, p<0.01). Positive response appearance time was 15.1+/-14.0
      minutes at 60 degrees  for vasovagal syncope children. There was no significant
      difference in the time to positive response, at different tilt angles during the
      head-up tilt test for vasovagal syncope or for postural orthostatic tachycardia
      syndrome. Hence, it is suggested that a tilt angle of 60 degrees  and head-up
      tilt test time of 45 minutes should be suitable for children with vasovagal
      syncope.

PMID- 24124667
TI  - Effects of transcranial direct current stimulation on risky decision making are
      mediated by 'hot' and 'cold' decisions, personality, and hemisphere.
AB  - Previous results point towards a lateralization of dorsolateral prefrontal cortex
      (DLPFC) function in risky decision making. While the right hemisphere seems
      involved in inhibitory cognitive control of affective impulses, the left DLPFC is
      crucial in the deliberative processing of information relevant for the decision.
      However, a lack of empirical evidence precludes definitive conclusions. The aim
      of our study was to determine whether anodal transcranial direct current
      stimulation (tDCS) over the right DLPFC with cathodal tDCS over the lDLPFC
      (anodal right/cathodal left) or vice versa (anodal left/cathodal right)
      differentially modulates risk-taking in a task [the Columbia Card Task (CCT)]
      specifically engaging affect-charged (Hot CCT) vs. deliberative (Cold CCT)
      decision making. The facilitating effect of the anodal stimulation on neuronal
      activity was emphasized by the use of a small anode and a big cathode. To
      investigate the role of individual differences in risk-taking, participants were
      either smokers or non-smokers. Anodal left/cathodal right stimulation decreased
      risk-taking in the 'cold' cognition version of the task, in both groups, probably
      by modulating deliberative processing. In the 'hot' version, anodal
      right/cathodal left stimulation led to opposite effects in smokers and non
      smokers, which might be explained by the engagement of the same inhibitory
      control mechanism: in smokers, improved controllability of risk-seeking
      impulsivity led to more conservative decisions, while inhibition of risk-aversion
      in non-smokers resulted in riskier choices. These results provide evidence for a
      hemispheric asymmetry and personality-dependent tDCS effects in risky decision
      making, and may be important for clinical research on addiction and depression. 

PMID- 24124666
TI  - Development of scaffold-free elastic cartilaginous constructs with structural
      similarities to auricular cartilage.
AB  - External ear reconstruction with autologous cartilage still remains one of the
      most difficult problems in the fields of plastic and reconstructive surgery. As
      the absence of tissue vascularization limits the ability to stimulate new tissue
      growth, relatively few surgical approaches are currently available (alloplastic
      implants or sculpted autologous cartilage grafts) to repair or reconstruct the
      auricle (or pinna) as a result of traumatic loss or congenital absence (e.g.,
      microtia). Alternatively, tissue engineering can offer the potential to grow
      autogenous cartilage suitable for implantation. While tissue-engineered auricle
      cartilage constructs can be created, a substantial number of cells are required
      to generate sufficient quantities of tissue for reconstruction. Similarly, as
      routine cell expansion can elicit negative effects on chondrocyte function, we
      have developed an approach to generate large-sized engineered auricle constructs
      (>=3 cm(2)) directly from a small population of donor cells (20,000-40,000
      cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated
      constructs adopted structural-like characteristics similar to native auricular
      cartilage, including the development of distinct cartilaginous and perichondrium
      like regions. Both alterations in media composition and seeding density had
      profound effects on the formation of engineered elastic tissue constructs in
      terms of cellularity, extracellular matrix accumulation, and tissue structure.
      Higher seeding densities and media containing sodium bicarbonate produced tissue
      constructs that were closer to the native tissue in terms of structure and
      composition. Future studies will be aimed at improving the accumulation of
      specific tissue constituents and determining the clinical effectiveness of this
      approach using a reconstructive animal model. 

PMID- 24124668
TI  - Penile metastasis from primary cholangiocarcinoma: the first case report.
AB  - BACKGROUND: Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has
      not been previously reported in the literature. Common metastatic sites for CCA
      include the regional lymph nodes and adjacent organs. CCAs are not highly
      vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA
      metastases commonly occur at distant organs such as the lungs, adrenal glands,
      and bones. Median survival for patients with metastatic disease is generally less
      than 1 year. CASE PRESENTATION: A 74-year-old Caucasian man consulted us after
      having undergone penile ultrasonography for pain and increased thickness at the
      base of the penis after self-examination. The patient presented with a history of
      hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously.
      A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring
      the same histological and immunophenotypical features as the primary hepatic
      lesion. CONCLUSIONS: To date, there is no case of penile or urogenital system
      metastasis from CCA described in the literature. Therefore, this article
      represents the first case report of penile metastasis from CCA.

PMID- 24124669
TI  - Oral health-related quality of life and traumatic dental injuries in Brazilian
      adolescents.
AB  - OBJECTIVES: To evaluate the impact of traumatic dental injuries (TDI) on oral
      health-related quality of life (OHRQoL) among Brazilian adolescents. METHODS: A
      population-based case-control study was carried out, which was nested to a cross
      sectional study with a sample of 1215 adolescents aged 11-14 years from Belo
      Horizonte, Brazil. OHRQoL was measured using the Brazilian version of the Child
      Perceptions Questionnaire (CPQ11-14 )--Impact Short Form (ISF:16). Two-step
      cluster analysis was performed to define cases and controls based on CPQ11-14-
      ISF:16 scores. This method considers the pattern of responses for each item
      separately and how important each item is to the formation of clusters. The case
      group included those adolescents who presented higher negative impact on OHRQoL
      (n=405), while the control group included those with lower negative impact
      (n=810). Two controls for each case were individually matched from the same
      school and gender. The main independent variable was TDI, diagnosed by the
      Andreasen's classification. Untreated dental caries, malocclusion, and age were
      confounding variables. Conditional logistic regression analysis was performed
      with the significance level set at 5%. RESULTS: A multiple conditional logistic
      regression model demonstrates that adolescents diagnosed with fracture involving
      dentin and/or pulp had a 2.40-fold greater chance of presenting high negative
      impact on QHRQoL [95% CI=1.26-4.58; P=0.008] than those without evidence of
      fractures. Enamel fracture only [P=0.065] and restored fractures [P=0.072] were
      not statistically associated with OHRQoL. CONCLUSIONS: Adolescents with more
      severe untreated TDI, such as fractures involving dentin and/or pulp, were more
      likely to self-report a higher negative impact on their OHRQoL than those without
      TDI.

PMID- 24124670
TI  - [Strategy on prevention and treatment of pulmonary hypertension during the
      Twelfth Five-Year Plan for National Economic and Social].

PMID- 24124671
TI  - [Clinical observation of cardiopulmonary exercise test in patients with
      idiopathic pulmonary arterial hypertension].
AB  - OBJECTIVE: To explore the exercise characteristics of patients with idiopathic
      pulmonary arterial hypertension (IPAH). METHODS: From November 2010 to September
      2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai
      Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise
      testing. The exercise parameters were compared. Correlations among peak oxygen
      consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association
      (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute
      walking distance (6 MWD) and cardiac index are analyzed in IPAH. RESULTS: There
      were 21 males and 55 females in IPAH and 8 males and 16 females in controls.
      Their mean ages were (31.5 +/- 10.6) and (35.5 +/- 6.4) years respectively.
      Significant differences (P = 0.000) existed between two groups in peak oxygen
      consumption ((12.7 +/- 3.3) vs (25.6 +/- 5.8) ml.min(-1).kg(-1)), anaerobic
      threshold ((9.8 +/- 2.5) vs (16.7 +/- 3.9) ml.min(-1).kg(-1)), peak oxygen pulse
      ((5.3 +/- 1.6) vs (9.9 +/- 2.5) ml/bpm) and ventilator efficiency (slope of
      minute ventilation in relation to CO2 produced) ((42.6 +/- 2.0) vs (25.5 +/-
      3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA
      class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels
      (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated
      with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT
      proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator
      efficiency were both correlated well with total pulmonary vascular resistance.
      Partial correlation analysis demonstrated that there were significant
      correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT
      proBNP levels and 6MWD after adjusting for age, gender and weight. CONCLUSIONS:
      Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in
      IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing
      safely the function of IPAH patients.

PMID- 24124672
TI  - [Application of cardiopulmonary exercise testing in patients with chronic
      thromboembolic pulmonary hypertension].
AB  - OBJECTIVE: To evaluate the application value of cardiopulmonary exercise testing
      in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS:
      A total of 116 consecutive patients admitted into the Cardiology Department of
      Fuwai Hospital.They were divided into 3 groups of CTEPH (n = 44), CPE (without
      pulmonary hypertension in chronic pulmonary embolism) (n = 24) and control
      (without pulmonary embolism or pulmonary hypertension) (n = 48) respectively.
      Their levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were
      measured. Incremental cardiopulmonary exercise testing was performed to compare
      its differential results among 3 groups and evaluate the correlation between NT
      proBNP and its parameters. RESULTS: The body mass index (BMI) in the CTEPH group
      was lower than those in the CPE and control groups ((23.8 +/- 3.9) vs (26.1 +/-
      3.6) and (26.7 +/- 3.2) kg/m(2) ), both P < 0.05); the medical history in the
      CTEPH group was longer than those in the CPE and control groups ((58 +/- 48) vs
      (12 +/- 10) and (29 +/- 25) months, both P < 0.05). The plasma concentrations of
      NT-proBNP in the CTEPH group were higher than those in the CPE and control groups
      ((1678 +/- 1255) vs (577 +/- 167) and (608 +/- 247) pmol/L, both P < 0.05). All
      of them completed the test and there were no severe complications such as syncope
      or exacerbation of disease. Maximum oxygen consumption (VO2max), percentage of
      predicted maximum oxygen consumption (VO2 %), oxygen consumption in relation to
      body weight (VO2/kg), anaerobic threshold and O2 pulse in the CTEPH group were
      significantly lower than those in the CPE and control groups (P < 0.05). The
      ratios of dead space volume (VD) to tidal volume (VT) in the CTEPH and CPE groups
      were higher than those in the control group (P < 0.05). The plasma concentrations
      of NT-proBNP were inversely correlated with right ventricular internal diameter
      (r = -0.690, P = 0.000) and VO2/kg (r = -0.496, P = 0.000). The right ventricular
      internal diameter (beta = 0.583, P = 0.000) and VO2/kg (beta = 0.233, P = 0.032)
      were strong independent determinants of NT-proBNP. CONCLUSION: As a reliable
      pathophysiological indictor of CTEPH, cardiopulmonary exercise testing may be
      used objectively and safely to evaluate the cardiopulmonary function of CTEPH
      patients.

PMID- 24124673
TI  - [Protective effects of beraprost plus simvastatin on monocrotaline-induced
      pulmonary arterial hypertension in rats].
AB  - OBJECTIVE: To explore the protective effects of beraprost plus simvastatin on
      monocrotaline-induced pulmonary arterial hypertension in rats. METHODS: Forty
      male Sprague-Dawley rats were allocated to control (C), untreated pulmonary
      arterial hypertension (P), beraprost (B), simvastatin (S) and combination groups
      (Com) (n = 8 each). Normal saline was injected subcutaneously into group C and
      then there was no other intervention for 21 days. Group P, B, S and Com rats
      received subcutaneous injections of monocrotaline (MCT, 60 mg/kg) and then
      isovolumetric normal saline, beraprost (100 ug.kg(-1).d(-1)), simvastatin (2
      mg.kg(-1).d(-1)) and beraprost (100 ug.kg(-1).d(-1)) plus simvastatin (2 mg.kg(
      1).d(-1)) by daily gastric lavage for 21 days. At Day 22, heart rate (HR), mean
      arterial pressure (MAP) and mean pulmonary pressure (mPAP) were detected and
      right heart ventricular hypertrophy index (RVHI) was calculated. The
      histopathology changes and tunica media thickness percentage of pulmonary
      arteries (WT%) were evaluated by pulmonary tissue staining. The results were
      analyzed statistically. RESULTS: The differences of HR and MAP were not
      significant among 5 groups (all P > 0.05). The levels of mPAP, RVHI and WT% in
      group B ((27.4 +/- 3.7) mm Hg, 0.35 +/- 0.03, 26.7% +/- 2.4%), group S ((29.9 +/-
      4.4) mm Hg, 0.36 +/- 0.03, 28.2% +/- 1.9%) and group Com ((23.1 +/- 3.9) mm Hg,
      0.32 +/- 0.03, 17.4% +/- 3.3%) were lower than those in group P ((35.4 +/- 5.7)
      mm Hg, 0.41 +/- 0.05, 42.8% +/- 5.9%) (all P < 0.05). CONCLUSIONS: The combined
      use of beraprost and simvastatin may delay the increase of mPAP and remodeling of
      pulmonary vessels and inhibit right ventricular hypertrophy in pulmonary arterial
      hypertension rats. Its efficacy is superior to that of monotherapy.

PMID- 24124674
TI  - [Study on the dendritic cell subsets in peripheral blood and its relationship
      with the expressions of Gata-3 and T-bet in lymphocytes of patients with immune
      thrombocytopenia].
AB  - OBJECTIVE: To explore the relationship between the dendritic cell (DC) subsets
      and abnormal expression of transcription factors Gata-3 and T-bet in patients
      with immune thrombocytopenia (ITP). METHODS: The plasmacytoid DC (pDC) and
      myeloid DC (mDC) of 33 ITP (16 untreated, 17 remitted) patients and 12 healthy
      controls were analyzed by flow cytometry (FCM) . The expressions of Gata-3 mRNA
      and T-bet mRNA in peripheral blood mononuclear cell (PBMNC) were detected by
      reverse transcription-polymerase chain reaction (RT-PCR) .The levels of
      interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were measured by FCM in 33
      ITP patients and 12 healthy controls. RESULTS: The percentage of pDC in PBMNC was
      0.49% +/- 0.18% in untreated and it was higher than that in remitted ITP patients
      (0.27% +/- 0.17%) and in controls (0.32% +/- 0.13%) (both P < 0.05). The
      percentage of mDC in PBMNC was 0.23% +/- 0.17% in untreated, which was lower than
      that in remitted ITP patients (0.33% +/- 0.18)% and in controls (0.31% +/-
      0.11%), but no statistic difference in mDC expression existed among 3 groups (P >
      0.05). pDC/mDC ratios was (3.15 +/- 2.01) in untreated ITP patients and it was
      higher than that in remitted ITP patients (0.81 +/- 0.32) and in controls (1.07
      +/- 0.44) (both P < 0.05). The relative mRNA expression levels of Gata-3 were
      2775 +/- 489, 1357 +/- 307 and 652 +/- 165 respectively. And the expression of
      Gata-3mRNA in untreated group was higher than that in remission group or healthy
      controls (both P < 0.05). The relative mRNA expression levels of T-bet were 782
      +/- 394, 583 +/- 176 and 576 +/- 120. No statistic difference in T-bet expression
      existed among 3 groups (P > 0.05). Gata-3mRNA/T-bet mRNA ratio was (4.13 +/- 1.69
      ) in untreated group and it was higher than that of remission group (2.45 +/-
      0.69) or controls (1.15 +/- 0.27) (both P < 0.05). The level of IL-4 in the
      untreated group was 9.14% +/- 4.34% and it was higher than that of remission
      group (4.78% +/- 1.69%) or controls (4.86% +/- 1.41%). The level of IFN-gamma in
      the untreated group was lower than that of controls (P < 0.05). Significant
      positive correlations existed between Gata-3 and pDC/mDC ratio (r = 0.585, P <
      0.01). Significant positive correlations existed between Gata-3 and IL-4 ( r =
      0.463, P < 0.05). CONCLUSION: The mechanism of ITP may be due to a disorder of DC
      subsets and a high expression of Gata-3.

PMID- 24124675
TI  - [Impact of diabetes on clinical outcomes following multivessel percutaneous
      interventions].
AB  - OBJECTIVE: To compare the rates of mortality, myocardial infarction (MI), repeat
      revascularization and stent thrombosis after percutaneous coronary intervention
      (PCI) with implantation of stents for diabetics versus nondiabetics with
      multivessel disease to evaluate the impact of diabetes on long-term clinical
      outcomes. METHODS: We consecutively recruited a total of 1985 patients with
      multivessel disease at our institution from July 2003 to December 2005. And they
      were divided into two groups of diabetes (n = 587) or non-diabetes (n = 1398).
      The primary endpoint was all-cause mortality at 24 months. RESULTS: After
      adjusting with Logistic regression, the risk of mortality in the diabetics was
      significantly higher than that in the nondiabetics (4.4% vs 2.0%, hazard ratio
      [HR] 1.83, 95% confidence interval [CI] 1.02 to 3.67, P = 0.021). Similar outcome
      was also found in the adjusted risk of cardiac mortality (2.7% vs 1.1%, HR =
      2.04, 95%CI 1.12 to 3.89, P = 0.032) at 24 months, although the adjusted risk of
      nonfatal MI and repeat revascularization was similar. However, diabetes
      significantly increased the risk of stent thrombosis. The major adverse cardiac
      event (MACE) rate was also lower in the nondiabetics (15.8% vs 11.9%, HR = 1.52,
      95%CI 1.12 to 1.89, P = 0.043). CONCLUSION: In patients with multivessel disease,
      diabetes is correlated with increase risks of mortality, stent thrombosis and
      MACE at long-term follow-up compared with non-diabetes.

PMID- 24124676
TI  - [Effects of neoadjuvant chemotherapy on the prognostic mortality risk of invasive
      transitional bladder cancer: a meta-analysis].
AB  - OBJECTIVE: To systematically assess the effects of neoadjuvant chemotherapy on
      the prognostic risk of invasive transitional bladder cancer. METHODS: All known
      randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment
      of invasive transitional bladder cancer, published from the date of database
      building to September 2012, were retrieved from such databanks as Pubmed,
      CBMdisc, Embase and Cochrane. The data on 5-year survival rate of included
      studies were extracted for further heterogeneity exploration, subgroup analysis
      and statistical pooling with the RevMan 5.10 software. RESULTS: Fourteen subjects
      involving 2072 cases and 2086 controls were published from 1991 to 2012. The
      overall odds ratio of survival suggested a 21% relative reduction in mortality
      risk for neoadjuvant chemotherapy compared to that on control (OR = 0.79,
      95%CI:0.70-0.90). In subgroup analysis according to different neoadjuvant
      chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC
      (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed
      significant benefit to overall survival with 28% and 25% reduction in risk of
      death respectively (OR = 0.72,95%CI:0.60-0.86, OR = 0.75,95%CI:0.59-0.96) .
      However, no significant difference existed in effects between C (cisplatin)
      chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and
      docetaxel) chemotherapy and controls. In subgroup analysis according to local
      treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the
      patients with cystectomy showed significant benefits in overall survival with 25%
      reduction in risk of death (OR = 0.75, 95%CI:0.65-0.87). However, the patients
      with radiotherapy or radiotherapy plus cystectomy showed no significant benefits
      in overall survival. CONCLUSIONS: MCV and MVAC neoadjuvant chemotherapies improve
      survival among patients with bladder cancer. And neoadjuvant chemotherapy has
      better long-term survival after cystectomy.

PMID- 24124677
TI  - [Analysis of associations between molecular subtypes and responses to neoadjuvant
      chemotherapy in primary breast cancer patients].
AB  - OBJECTIVE: To explore the correlations between molecular subtypes and responses
      to neoadjuvant chemotherapy in primary breast cancer patients. METHODS: The core
      needle biopsy specimens were collected from 563 patients undergoing 4-8 cycles of
      neoadjuvant chemotherapy between January 2001 to January 2009. And
      immunohistochemical assays were employed to detect the levels of estrogen
      receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor
      2 (HER2) and Ki-67 proliferation index simultaneously. Molecular subtypes were
      divided on the basis of immunohistochemical results. And the associations between
      molecular subtypes and responses to neoadjuvant chemotherapy were analyzed in 563
      patients. RESULTS: The pathological complete response (pCR) rates of patients
      with hormone receptor-negative/HER2-negative subtype (HR-/HER2-) , HER2-positive
      subtype (HER2+) and hormone receptor-positive/HER2-negative subtype (HR+/HER2-)
      were 38.9%, 17.9% and 8.3% respectively. In univariate analysis, there were
      significant differences in pCR rates among the groups (P < 0.001) . In
      multivariate analysis, the patients with HER2+ subtype had a significantly higher
      pCR rate than those with HR+/HER2- subtype (OR = 0.344, P = 0.002) . Whereas the
      patients with HER2+ subtype had a significantly lower pCR rate than those with HR
      /HER2- subtype (OR = 2.453, P = 0.007) . Among HR+/HER2-subtypes, a higher pCR
      rate was observed in the group of high expression level of Ki-67 proliferation
      index (Ki-67 >= 20%) (P = 0.004) . But no significant differences existed in pCR
      rates between the group of high expression level of hormone receptor and the
      group of non-high expression level (P = 0.256) . CONCLUSION: There were
      correlations between molecular subtypes and responses to neoadjuvant chemotherapy
      in primary breast cancer patients. Patients of HER2+and HR-/HER2- subtype are
      more likely to respond to neoadjuvant chemotherapy. Among HR+/HER2-subtypes,
      those with a high level of Ki-67 proliferation index tend to benefit from
      neoadjuvant chemotherapy.

PMID- 24124678
TI  - [Characteristics of lung function in preterm infants with varying degrees of
      bronchopulmonary dysplasia].
AB  - OBJECTIVE: To explore the characteristics of lung function in preterm infants
      with varying degrees of bronchopulmonary dysplasia(BPD). METHODS: There were 407
      infants (278 males and 129 females) were recruited from Shenzhen Children'
      Hospital between January 2011 and October 2012.Among them 188 term infants (term
      group)and 113 preterm infants (non-BPD preterm group) were selected as controls.
      A total of 106 BPD infants from the observation group were divided into mild(n =
      48), moderate (n = 42) and severe(n = 16) sub-groups according to the definition
      of BPD. Infants with diseases interfering with lung function, such as congenital
      heart disease, congenital diaphragmatic hernia, or thoracic wall deformities,
      were excluded. Lung function was tested at a postmenstrual age (PMA) of 44
      weeks.q test, Dunnett C test and Spearman analysis were used for statistical
      analysis. RESULTS: The age range was 17-116 d, test weight range 1.83-7.00 kg and
      test height range 40.0-64.0 cm.In non-BPD preterm group, the respiratory rate
      (RR) was higher than that in term group ((50 +/- 13) vs (44 +/- 10) times/min,P <
      0.01) ,while the tidal volume(TV), ratio of time to peak tidal expiratory time
      and expiratory time (Tpef/Te) and peak expiratory flow(TPEF) were all less than
      those in term group ((25 +/- 9) vs (29 +/- 7)ml,29% +/- 9% vs 33% +/- 8%, (59 +/-
      23) vs (65 +/- 25)ml/s,all P < 0.05) .Neither functional residual capacity(FRC)
      nor lung clearance index (LCI) had significant statistical difference between two
      groups ((20 +/- 5) vs (19 +/- 5)ml/kg, 8.4 +/- 2.8 vs 8.7 +/- 3.4, all P > 0.05))
      . In moderate and severe BPD groups, RR ((57 +/- 9), (58 +/- 10) times/min) were
      both higher than that in non-BPD group(both P < 0.05) while RR in mild group ((53
      +/- 13)times/min)had no statistical significant difference with non-BPD group (P
      > 0.05). The values of TV and LCI in mild, moderate and severe BPD groups have no
      statistical significance with non-BPD group (all P > 0.05). Except for mild BPD
      group(24% +/- 13%, (18 +/- 5)ml/kg), Tpef/Te and FRC in both moderate and severe
      groups (20% +/- 9% and 18% +/- 5%, (15 +/- 3)and (15 +/- 4)ml/kg)were less than
      those in non-BPD group(all P < 0.05). Only in severe BPD group ((85 +/- 11)ml/s),
      TPEF was higher than that in non-BPD group(P < 0.05). Correlation analysis showed
      that, except for LCI, all of these parameters were significantly associated with
      the degree of BPD(all P < 0.05). CONCLUSIONS: For BPD and non-BPD preterm
      infants, there are various changes in respiratory rhythm, lung volume,
      ventilation inhomogeneity, ventilatory efficiency and small airway resistance.
      The increases of pulmonary elastic recoil and degree of major airway constriction
      are obvious in moderate and severe BPD infants.

PMID- 24124679
TI  - [Clinical research of Bordetella pertussis infection in infants with prolonged
      cough].
AB  - OBJECTIVE: To explore the prevalence of Bordetella pertussis (B. pertussis)
      infection in unvaccinated or incomplete vaccinated infants with cough for a
      prolonged duration. METHODS: The serum samples and nasopharyngeal secretions were
      collected from 176 patients with cough for a prolonged duration ( >= 2 weeks)
      from 2011 to 2012 at Children's Hospital Affiliated to Capital Institute of
      Pediatrics. Multiplex PCR of nasopharyngeal secretion was employed to identify
      B.pertussis. And enzyme-linked immunosorbent assay(ELISA) was used to detect
      antibody to pertussis toxin(PT-IgG). Total bacterial DNA was enacted from
      nasopharyngeal secretion and two-target IS481/PT of B.pertussis was detected by
      PCR. The sera and nasopharyngeal secretions were also collected from household
      contacts with cough for a prolonged duration. Their clinical characteristic and
      epidemiological profiles were collected and analyzed. RESULTS: B.Pertussis
      infection was demonstrated in 51 cases (29.0%). The patients ages were from 23
      days to 4 years. Among them, 46 cases (90.2%) were aged under 12 months and 5
      cases (9.8%) over 12 months. And 40 cases were unvaccinated (31 cases <3 months
      old, 4 cases 3-12 months old, 5 cases >5 years old) and 11 cases incompletely
      vaccinated. There were 31 males and 20 females. More patients were found in
      spring and summer than those in autumn and winter. Nine infant cases had 12
      household contacts. Among 12 household contacts, 3 were PCR positive and 12 PT
      IgG positive. Pertussis was remarkably critical in infants. Serious complications
      included failure to thrive, pneumonia, respiratory failure and seizures.
      CONCLUSIONS: B.pertussis infection is an important cause in unvaccinated or
      incomplete vaccinated infants with prolonged cough. Peak seasons of pertussis are
      spring and summer. Undiagnosed adolescents and adults with pertussis may be a
      significant source for transmission of B.pertussis to other susceptible children.
      Infants aged under 1 year are at risk for severe pertussis and life-threatening
      complications. As a rapid and sensitive method of detecting B.pertussis, PCR may
      be used in early phase.

PMID- 24124680
TI  - [Assessment of prognostic and influencing factors in elderly patients with
      multiple organ dysfunction syndrome].
AB  - OBJECTIVE: To preliminarily assess the prognosis of patients with multiple organ
      dysfunction syndrome (MODSE) and analyze their influencing factors. METHODS: The
      clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital
      during January 2009 to June 2012 were analyzed retrospectively. According to 28
      day outcomes, they were divided into 2 groups (28-day survival and non-survival)
      while 4 groups according to age. Then these prognosis were evaluated with the
      current scoring systems ((acute physiology and chronic health evaluation II
      (APACHEII and III), sample acute physiological score (SAPSII) and multiple organ
      dysfunction score (MODS)). The predictive powers were compared by receiver
      operating characteristic (ROC) curve. Finally a binary Logistic regression
      analysis was performed to evaluate the relevant influencing prognostic factors of
      MODSE. RESULTS: The mean age was (77.8 +/- 9.1) years, mean number of failed
      organs (3.6 +/- 1.2) and a 28-day mortality 45.8%. The ages of non-survival group
      were older than those of survival group ((78.1 +/- 9.1) vs (76.7 +/- 11.0)
      years). The number of organ failures ((4.3 +/- 1.1) vs (3.1 +/- 1.0)) and scores
      (APACHEII: (28 +/- 7) vs (20 +/- 8), APACHE III: (106 +/- 27) vs (75 +/- 31),
      SAPSII: (64 +/- 16) vs (46 +/- 18), MODS: (9 +/- 3) vs (6 +/- 3)) of non
      survivals were significantly higher than that of survivals. The area under ROC
      curve of these four score systems were 0.790, 0.781, 0.780 and 0.780
      respectively. Compared to the above systems, SAPSII had the best performance in
      sensitivity while APACHEII was more valuable in specificity. All clinical data
      underwent binary Logistic regression and the results showed that plasma
      concentration of albumin and mean arterial pressure (MAP) offered beneficial
      outcomes while age and number of organ failures had unfavorable prognosis. The
      greater patient age, the higher their mortality. CONCLUSIONS: All four scoring
      systems have accurate prognostic predictions of MODSE patients. And the
      predictive power of APACHEII is the best. Plasma concentration of albumin, MAP,
      age and organ failure number are independent prognostic factors in MODSE
      patients.

PMID- 24124681
TI  - [Comparative study of three types of anatomical vascular occlusion method in
      hepatectomy for liver neoplasms].
AB  - OBJECTIVE: To assess the clinical efficacies of three types of anatomical hepatic
      inflow occlusion method in hepatectomy for liver neoplasms. METHODS: A non
      randomized concurrent controlled trial was performed from January 2011 to October
      2012, a total of 180 consecutive patients with liver neoplasms underwent
      hepatectomy similarly. They were divided into 3 groups according to the hepatic
      inflow occlusion methods during resection: HHV group (hemi-hepatic vascular
      inflow occlusion, n = 60), MPV group (main portal vein inflow occlusion, n = 60)
      and HPP group (hemi-portal vein preserved inflow occlusion, n = 60). The primary
      endpoints were intraoperative blood loss and transfusion requirement while the
      secondary outcomes were assessed with operating duration, postoperative
      morbidity, hospital stay, gastrointestinal function and postoperative liver
      injury. RESULTS: No significant differences existed among three groups in
      demographic and tumor characteristics and operation-related background (P >
      0.05). No mortality happened in 30 days postoperatively in all patients.
      Intraoperative volume of blood loss had no significant differences among three
      groups (P = 0.272). Among the patients requiring transfusion, HPP group had the
      least transfusion requirement (HHV group: (5.00 +/- 1.51) U, MPV group:(3.50 +/-
      1.41) U, HPP group: (2.50 +/- 0.93) U, P = 0.004). MPV group showed a significant
      shorter operating duration (HHV group: (227 +/- 59) min, MPV group:(198 +/- 56)
      min, HPP group:(221 +/- 79) min, P = 0.042). No significant differences were
      found among three groups in hospital stay (P = 0.673) or postoperative morbidity
      (P = 0.735), including hepatic insufficiency, infection and ascites. HHV group
      showed an earlier recovery of gastrointestinal function (HHV group: (60 +/- 12)
      h, MPV group:(69 +/- 9) h, HPP group:(64 +/- 8) h, P = 0.000).MPV group had a
      significantly lower level of aminotransferase at Day 1 and 3 postoperation (d1
      ALT: HHV group: (403 +/- 271) U/L, MPV group:(304 +/- 211) U/L, HPP group: (448
      +/- 396) U/L, P = 0.033; d1 AST: HHV group: (394 +/- 271) U/L, MPV group:(278 +/-
      189) U/L, HPP group: (432 +/- 405) U/L, P = 0.017; d3 ALT: HHV group: (309 +/-
      193) U/L, MPV group:(232 +/- 161) U/L, HPP group:(325 +/- 277) U/L, P = 0.048; d3
      AST: HHV group:(136 +/- 105) U/L, MPV group:(91 +/- 73) U/L, HPP group:(120 +/-
      87) U/L, P = 0.024).But no significant differences were found among three groups
      regarding total bilirubin, albumin, prealbumin and prothrombin time activity (P <
      0.05) during any postoperative stage. CONCLUSION: All three types of anatomical
      vascular occlusion method are both safe and efficacious in hepatectomy. But no
      single method has absolute advantage over the other two. HPP method has the best
      hemostatic effect, MPV offers better postoperative liver function and HHV
      promotes early recovery of gastrointestinal function.

PMID- 24124682
TI  - [Effects of distance between residence and hemodialysis unit on cardiovascular
      complications and treatments of maintenance hemodialysis patients].
AB  - OBJECTIVE: To explore the effects of etiological classification and the distance
      between residence and hemodialysis unit on cardiovascular complications and
      treatments in maintenance hemodialysis (MHD) patients. METHODS: A total of 756
      MHD patients were collected from 12 hemodialysis centers of Guiyang, China
      between January 2011 and May 2012. Their distribution characteristics and
      correlations were based on medical records. And statistical analyses were
      performed. RESULTS: The ratio of males and females was 1.45: 1. And their mean
      age was (49.1 +/- 14.7) years old. And 496 (65.6%) cases suffered from
      cardiovascular complications. The analysis of multi-factor Logistic regression
      revealed that distance between residence and dialysis unit was an independent
      risk factor of cardiovascular complications. The group of the farthest distance (
      > 30 km) had the worst influence on dialysis adequacy Kt/V score, urea clearance
      rate, dialysis frequency and time per week. And the levels of blood phosphorus,
      triglyceride and cholesterol in the fourth group had marked elevations. It had a
      significant positive correlation with distance (P < 0.05). CONCLUSION: The
      distance between residence and dialysis unit is an independent risk factor of
      cardiovascular complications in MHD patients. The farthest distance ( > 30 km)
      has the greatest influence on dialysis adequacy.

PMID- 24124683
TI  - [Risk factors for failure of continuous veno-venous hemodialysis in the treatment
      of acute kidney injury following cardiac surgery].
AB  - OBJECTIVE: To evaluate the independent risk factors for failure of continuous
      veno-venous hemodialysis (CVVHD) in the treatment of acute kidney injury (AKI)
      following cardiac surgery. METHODS: Adult patients without any prior pre
      operative history of chronic renal disease suffering AKI following cardiac
      surgery and undergoing CVVHD at our center from January 2005 to December 2012
      were recruited and divided into either a success group or a failure group. All
      pre-, intra- and post-operative data were collected and retrospectively analyzed.
      RESULTS: Ninety-three adult patients were enrolled. Among them, sixty-three
      patients survived with a failure rate of 32.2% and a mortality rate of 19.4%.
      Through univariate analysis and multivariate Logistic regression, independent
      risk factors for failure of CVVHD in the treatment of post-operative AKI included
      pre-operative LVEF (OR = 0.61, 95%CI 0.42-0.85) and duration of oliguria until
      dialysis (OR = 2.76, 95%CI 1.51-5.83). CONCLUSION: Pre-operative impaired left
      ventricular function is an important risk factor for failure of CVVHD in the
      treatment of AKI after cardiac surgery. The sooner the implementation of CVVHD,
      the better prognosis.

PMID- 24124684
TI  - [Application of one-stop diagnosis and treatment plan in percutaneous
      nephrolithotomy for patients with complex renal calculi].
AB  - OBJECTIVE: To evaluate the safety and efficacy of preoperative computed
      tomography urography (CTU) three-dimensional reconstruction, intraoperative
      radiology and ultrasound guidance followed by percutaneous nephrolithotomy (PCNL)
      in the treatment of complex renal calculi. METHODS: We summarized the clinical
      data of 210 patients with complex renal calculi treated at our hospital from
      December 2008 to December 2011 in this retrospective study. In the one-stop
      diagnosis and treatment group (n = 119), the optimal puncture approach was
      designed according to CTU imaging and three-dimensional reconstruction.
      Percutaneous track was established by ultrasound and radiology guided puncture.
      PCNL was performed with EMS system. The control group (n = 91) underwent PCNL
      without radiological guidance. The success rate of puncture, mean accessing time,
      mean operative duration, intraoperative volume of blood loss and stone-free rate
      after one operative session were observed. Post-operative follow-ups were
      conducted until June 2012. RESULTS: Compared to the control group, the one-stop
      diagnosis and treatment group showed a higher success rate of puncture [98.3%
      (117/119) vs 92.3% (84/91), P = 0.037], a shorter operative duration [97.8 +/-
      13.20 vs 110.0 +/- 14.73 min, P = 0.043] and a higher stone-free rate after one
      operative session [92.4% (110/119) vs 83.5% (76/91), P = 0.037]. No significant
      difference was detected in the mean accessing time[15.3 +/- 3.7 vs 13.9 +/- 3.9
      min, P = 0.398] or intraoperative volume of blood loss [195.8 +/- 84.15 vs 263.3
      +/- 82.06 ml, P = 0.059]. No severe complications occurred. No recurrence of
      calculi was noted during the follow-up period. CONCLUSION: One-stop diagnosis and
      treatment plan (CTU 3-D reconstruction plus radiology, ultrasound guidance
      followed by PCNL) may identify the puncture path, improve the successful rate of
      puncture and stone-free rates and reduce the complications of PCNL.

PMID- 24124685
TI  - [Study of blood oxygen saturation, heart rate changes and plateau reaction of the
      Antarctic Kunlun station investigation team in different plateau environments].
AB  - OBJECTIVE: To explore the blood oxygen saturation and heart rate changes of the
      Antarctic explorers. METHODS: During August 2010 to April 2011, the changes in
      blood oxygen saturation, heart rate and plateau reaction of 16 Antarctic
      expedition team in different plateau environments (Tibetan plateau versus
      Antarctic plateau) were monitored with the noninvasive pulse oximeter MD300-C.
      The extent of acute mountain sickness was determined according to the Lake Louise
      Consensus acute mountain reaction symptom scores and judgment method. RESULTS:
      The changes of blood oxygen saturation, heart rate at different altitudes of 110,
      3650, 4300 m (96.8% +/- 1.2%,89.1% +/- 1.2%, 86.1% +/- 2.0%, (75.0 +/- 5.4)
      times/min, (104.0 +/- 4.3) times/min, (113.0 +/- 5.2) times/min,F = 214.155,
      240.088,both P < 0.05). With rising latitude and elevation gradient in Antarctic
      plateau, the changes of blood oxygen saturation, heart rate at different
      altitudes of 2000, 2500, 3000, 3500 and 4087 m(91.9% +/- 1.3%,90.5% +/-
      1.3%,87.6% +/- 1.4%,85.0% +/- 1.8%,81.5% +/- 2.2%, (85.9 +/- 3.2) times/min,
      (90.6 +/- 2.8) times/min, (97.8 +/- 4.1) times/min, (102.0 +/- 3.4) times/min,
      (106.3 +/- 3.9) times/min, F = 105.418, 90.174, both P < 0.05). Levels of blood
      oxygen saturation and heart rate were both correlated with the risk of altitude
      sickness (r = -0.446 and 0.565, both P < 0.05). CONCLUSIONS: As the increases of
      altitude, there are significant changes in oxygen saturation, heart rate of the
      Antarctic explorers. And with the increases of altitude, the risk of altitude
      sickness gradually increases.

PMID- 24124686
TI  - [Role of c-Myc in mesenchymal stromal cell-mediated drug resistance in acute
      leukemia cells].
AB  - OBJECTIVE: To explore the role of c-Myc in mesenchymal stromal cell-mediated drug
      resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML)
      from the version of tumor microenvironment. METHODS: AML cell lines U937 and KG1a
      were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy
      donors between January to March 2012. The AML cell lines plated alone was
      cultured as controls. Apoptosis induced by mitoxantrone was measured by flow
      cytometry and Annexin V/PI double and 4'-6-diamidino-2-phenylindole (DAPI)
      staining. And c-Myc protein was detected by Western blot under both culturing
      conditions. After a pre-treatment of c-Myc inhibitor 10058-F4, the apoptosis of
      AML cell was also evaluated. RESULTS: Apoptosis of AML cells (U937 and KG1a)
      significantly decreased during co-culturing with MSC (9.88% +/- 1.53% vs 42.83%
      +/- 2.03%, P = 0.004;20.60% +/- 2.87% vs 42.53% +/- 5.29%, P = 0.030). Drug
      resistance was implicated. The co-culturing of AML cells with MSC significantly
      induced an up-regulation of c-Myc. The inhibition of c-Myc with 10058-F4 could
      induce apoptosis of AML cells. After an addition of 10058-F4 into the co-culture
      system, the apoptotic rate of KG1a cells significantly increased from 23.87% +/-
      1.55% to 57.23% +/- 3.88% (P = 0.009). Similarly the apoptotic rates spiked from
      16.07% +/- 2.11% to 53.47% +/- 4.08% in U937 cells (P = 0.004) to overcome the
      stromal cell-mediated drug resistance. CONCLUSIONS: The co-culturing of AML cells
      and MSC induces an up-regulation of c-Myc protein so as to cause the emergence of
      chemoresistance. Therefore targeting c-Myc protein may provide a novel
      therapeutic strategy of AML.

PMID- 24124687
TI  - [Effects of selective inhibition of reverse mode of Na(+)/Ca(2+) exchanger on
      rats with contrast-induced acute kidney injury].
AB  - OBJECTIVE: Intracellular Ca(2+) overload is a key factor in contrast-induced
      renal tubular toxicity. Na(+)/Ca(2+) exchanger (NCX) system is one of main
      pathways of intracellular Ca(2+) overload. We explore the effects of KB-R7943, an
      inhibitor of reverse mode of NCX, on contrast-induced acute kidney injury (CI
      AKI). METHODS: Rats were divided into control, CI-AKI and pre-treatment groups
      with KB-R7943 (5, 10 mg/kg). CI-AKI was induced by diatrizoate administration in
      rats with cholesterol-supplemented diet for 8 weeks. Renal function and
      hemodynamics were determined at Day 1 post-administration. Renal histopathology
      was observed under light microscope. Renal tubular apoptosis was examined by
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Renal
      endothelin-1 (ET-1) was measured by radioimmunoassay. The oxidative markers of
      renal malondialdehyde (MDA) and catalase (CAT) were measured. The expression of
      NCX was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: Levels of serum creatinine (Scr, umol/L ) in CI-AKI rats ((149 +/- 35)
      umol/L) were significantly higher than those of normal rats ((55 +/- 4) umol/L, P
      < 0.01). Renal ET-1, MDA and CAT, resistance index (RI) of renal blood vessels
      increased significantly in CI-AKI rats. The contrast-induced increases in Scr and
      RI of renal blood vessels were suppressed significantly and dose-dependently by
      pretreatment with KB-R7943. Histopathological and TUNEL results showed that
      contrast-induced severe renal tubular necrosis and apoptosis were significantly
      and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed
      the contrast-induced increments of ET-1, MDA and CAT. No significant changes in
      NCX1 mRNA expression were observed following contrast administration. CONCLUSION:
      Renal oxidative stress and ET-1 overproduction via the activation of reverse mode
      of NCX play an important role in the pathogenesis of CI-AKI. And inhibition of
      reverse mode of NCX expressed in renal tubular epithelial cell has protective
      effects on CI-AKI.

PMID- 24124688
TI  - Gene identification programs in bread wheat: a comparison study.
AB  - Seven ab initio web-based gene prediction programs (i.e., AUGUSTUS, BGF, Fgenesh,
      Fgenesh+, GeneID, Genemark.hmm, and HMMgene) were assessed to compare their
      prediction accuracy using protein-coding sequences of bread wheat. At both
      nucleotide and exon levels, Fgenesh+ was deduced as the superior program and BGF
      followed by Fgenesh were resided in the next positions, respectively. Conversely,
      at gene level, Fgenesh with the value of predicting more than 75% of all the
      genes precisely, concluded as the best ones. It was also found out that programs
      such as Fgenesh+, BGF, and Fgenesh, because of harboring the highest percentage
      of correct predictive exons appear to be much more applicable in achieving more
      trustworthy results, while using both GeneID and HMMgene the percentage of false
      negatives would be expected to enhance. Regarding initial exon, overall, the
      frequency of accurate recognition of 3' boundary was significantly higher than
      that of 5' and the reverse was true if terminal exon is taken into account.
      Lastly, HMMgene and Genemark.hmm, overall, presented independent tendency against
      GC content, while the others appear to be slightly more sensitive if GC-poor
      sequences are employed. Our results, overall, exhibited that to make adequate
      opportunity in acquiring remarkable results, gene finders still need additional
      improvements. 

PMID- 24124689
TI  - Efficient electrophilic fluorination for the synthesis of novel 2'-fluoro-3'
      methyl-5'-deoxyphosphonic acid apiosyl nucleoside analogues.
AB  - Novel 5'-deoxyapiosyl purine phosphonic acid analogues with a 2'-electropositive
      moiety, such as, a fluorine atom were designed and synthesized from commercially
      available hydroxylacetone. Condensation of a glycosyl donor 10 with purines under
      Vorbruggen conditions and cross-metathesis give the desired nucleoside phosphonic
      acid analogues 14, 17, 21, and 24. The synthesized nucleoside analogues were
      subjected to antiviral screening against HIV-1, and the adenine analogue 17
      exhibited weak in vitro anti-HIV-1 activity (EC50=26.6 MUM).

PMID- 24124690
TI  - Phosphorylation of nucleoside-metallacarborane and carborane conjugates by
      nucleoside kinases.
AB  - A library of purine and pyrimidine nucleosides modified with carborane or
      metallacarborane boron clusters at different locations, consisting of new
      molecules as well as already described compounds, was prepared. The compounds
      were tested as substrates for human deoxynucleoside kinases. Some conjugates,
      with modification attached to N3 of thymidine via a linker containing the
      triazole moiety, were efficiently phosphorylated by cytosolic thymidine kinase 1
      and mitochondrial thymidine kinase 2. Higher phosphorylation levels were observed
      with thymidine kinase 1, the phosphorylation of nucleosides modified with
      metallacarboranes was observed for the first time. 

PMID- 24124691
TI  - Octreotide for acromegaly treatment: a reappraisal.
AB  - INTRODUCTION: Acromegaly is a rare disorder characterized by excess secretion of
      growth hormone (GH) generally caused by a pituitary macroadenoma and associated
      with reduced life expectancy if the disease is untreated. This article covers the
      recent available evidences published on octreotide , the first somatostatin
      analog introduced into clinical practice for the medical treatment of acromegaly.
      AREAS COVERED: This article discusses i) pharmacology of somatostatin and
      octreotide; ii) biochemical effects of regular octreotide and long-acting
      repeatable formulation; iii) tumor shrinkage effects of octreotide in acromegaly;
      iv) impact of octreotide on acromegalic clinical manifestations and chronic
      complications; v) safety of octreotide and vi) place of octreotide in the
      guidelines for acromegaly treatment. Full-text articles in the English language
      were selected from a PubMed search spanning 1984 - 2013, for keywords including
      'octreotide,' 'acromegaly,' 'GH,' 'IGF-I,' and 'tumor shrinkage.' Reference lists
      in selected papers were also used to broaden the search. EXPERT OPINION:
      Octreotide is a mature drug with a consolidated favorable benefit versus risks
      profile in the treatment of acromegaly.

PMID- 24124692
TI  - Tracking groundwater discharge to a large river using tracers and geophysics.
AB  - Few studies have investigated large reaches of rivers in which multiple sources
      of groundwater are responsible for maintaining baseflow. This paper builds upon
      previous work undertaken along the Fitzroy River, one of the largest perennial
      river systems in north-western Australia. Synoptic regional-scale sampling of
      both river water and groundwater for a suite of environmental tracers ((4) He,
      (87) Sr/(86) Sr, (222) Rn and major ions), and subsequent modeling of tracer
      behavior in the river, has enabled definition and quantification of groundwater
      input from at least three different sources. We show unambiguous evidence of both
      shallow "local" groundwater, possibly recharged to alluvial aquifers beneath the
      adjacent floodplain during recent high-flow events, and old "regional"
      groundwater introduced via artesian flow from deep confined aquifers. We also
      invoke hyporheic exchange and either bank return flow or parafluvial flow to
      account for background (222) Rn activities and anomalous chloride trends along
      river reaches where there is no evidence of the local or regional groundwater
      inputs. Vertical conductivity sections acquired through an airborne
      electromagnetic (AEM) survey provide insights to the architecture of the aquifers
      associated with these sources and general groundwater quality characteristics.
      These data indicate fresh groundwater from about 300 m below ground
      preferentially discharging to the river, at locations consistent with those
      inferred from tracer data. The results demonstrate how sampling rivers for
      multiple environmental tracers of different types-including stable and
      radioactive isotopes, dissolved gases and major ions-can significantly improve
      conceptualization of groundwater-surface water interaction processes,
      particularly when coupled with geophysical techniques in complex hydrogeological
      settings. 

PMID- 24124693
TI  - Genetic testing and Alzheimer's disease: implications for psychiatric-mental
      health nursing.
AB  - Alzheimer's disease (AD), the most common cause of irreversible dementia,
      continues to grow in prevalence as well as public health impact. Extensive
      research into the genetic etiology of AD has yielded knowledge of some genetic
      factors that are causative and other genetic factors that increase risk for
      disease. Consequently, the possibility of genetic testing in individuals with or
      at risk for AD is a question that nurses may be asked. Psychiatric-mental health
      (PMH) professionals are in key positions to influence the care of individuals who
      are considering the effect of genetic information on their health care decisions.
      Whether by working within interdisciplinary genetic counseling teams to provide
      direct specialty services or by developing skills to identify and refer
      individuals at risk for or concerned about their risk for AD, PMH nurses can play
      an important role in the health care of individuals and families experiencing AD.

PMID- 24124694
TI  - Concern for truth: driving defensively when confronting a zombie epidemic.
AB  - The newly approved drug Diclegis((r)), indicated for the treatment of nausea and
      vomiting associated with pregnancy, has a very interesting background story going
      back more than 50 years, in which science, celebrity individuals, the media, and
      the courts crossed paths. The story illustrates how concepts of truth, evidence,
      objectivity, and disinterested inquiry can become distorted in various ways, and
      this is especially relevant and prevalent in today's media environment of cable
      television, talk radio, and especially the Internet.

PMID- 24124695
TI  - Essential palatal myoclonus following dental surgery: a case report.
AB  - INTRODUCTION: Various presentations of essential palatal myoclonus, a condition
      characterized by clicking noises and palatal muscle spasm, have been reported in
      the literature. We are reporting the first case of essential palatal myoclonus
      following dental treatment. CASE PRESENTATION: A 31-year-old Caucasian man
      presented to our Ear, Nose and Throat department complaining of objective
      clicking tinnitus occurring immediately after he had undergone root canal
      treatment on his right lower third molar 3 months ago. Magnetic resonance imaging
      of his head revealed no abnormalities in the cerebrum, cerebellum or brainstem
      making the diagnosis essential palatal myoclonus. He returned a week later, and
      20 units of botulinum toxin A (Allergan) were injected into his left tensor veli
      palatine muscle. He reported an immediate improvement; however, symptoms recurred
      6 months later. CONCLUSIONS: Dental treatment can be a trigger of essential
      palatal myoclonus. Botulinum toxin injections are an effective treatment for
      short-term relief of symptoms.

PMID- 24124696
TI  - Health policy and systems research in access to medicines: a prioritized agenda
      for low- and middle-income countries.
AB  - OBJECTIVES: To identify priority policy issues in access to medicines (ATM)
      relevant for low- and middle-income countries, to identify research questions
      that would help address these policy issues, and to prioritize these research
      questions in a health policy and systems research (HPSR) agenda. METHODS: The
      study involved i) country- and regional-level priority-setting exercises
      performed in 17 countries across five regions, with a desk review of relevant
      grey and published literature combined with mapping and interviews of national
      and regional stakeholders; ii) interviews with global-level stakeholders; iii) a
      scoping of published literature; and iv) a consensus building exercise with
      global stakeholders which resulted in the formulation and ranking of HPSR
      questions in the field of ATM. RESULTS: A list of 18 priority policy issues was
      established following analysis of country-, regional-, and global-level
      exercises. Eighteen research questions were formulated during the global
      stakeholders' meeting and ranked according to four ranking criteria (innovation,
      impact on health and health systems, equity, and lack of research). The top three
      research questions were: i) In risk protection schemes, which innovations and
      policies improve equitable access to and appropriate use of medicines,
      sustainability of the insurance system, and financial impact on the insured? ii)
      How can stakeholders use the information available in the system, e.g., price,
      availability, quality, utilization, registration, procurement, in a transparent
      way towards improving access and use of medicines? and iii) How do policies and
      other interventions into private markets, such as information, subsidies, price
      controls, donation, regulatory mechanisms, promotion practices, etc., impact on
      access to and appropriate use of medicines? CONCLUSIONS: Our HPSR agenda adopts a
      health systems perspective and will guide relevant, innovative research, likely
      to bear an impact on health, health systems and equity.

PMID- 24124697
TI  - Interprovider variation of celiac disease testing in childhood chronic abdominal
      pain.
AB  - BACKGROUND: To determine within one tertiary care center: 1) the variation
      between providers in testing for celiac disease in children with chronic
      abdominal pain; 2) the characteristics of those children who were more likely to
      be tested, and 3) the prevalence of celiac disease in those evaluated. METHODS:
      Retrospective review of children with a primary complaint of chronic abdominal
      pain referred to a tertiary care children's hospital for pediatric
      gastroenterology evaluation over a 2-year period was conducted. Children with at
      least two visits and without an identified organic etiology for the pain were
      included. RESULTS: 160 children were evaluated by 16 pediatric
      gastroenterologists and one nurse practitioner. Celiac serologic testing was
      completed in 63 (39.4%) children. There was no significant variance in the
      frequency of celiac serologic testing between providers. Child age, gender, body
      mass index, and baseline gastrointestinal symptoms did not predict whether celiac
      serologic testing occurred, though Caucasians (P < 0.01) were more likely to be
      tested. Eighty-two (51.3%) children underwent either serologic testing and/or
      esophagogastroduodenoscopy. Four (4.9%, 95% CI: 1.6-11.3%) of the 82 tested were
      diagnosed with celiac disease. CONCLUSIONS: Though interprovider variation for
      celiac disease testing in children with chronic abdominal pain did not occur, a
      large number of these children were not evaluated for celiac disease. Children's
      race/ethnicity but not their associated gastrointestinal symptoms predicted
      whether celiac testing was undertaken. In those tested, celiac disease was
      identified in a higher percentage than that expected in the general population.

PMID- 24124698
TI  - Interrupted aorta diagnosed in a 51-year-old woman.
AB  - A 51-year-old lady presented with increasing heart failure symptoms and
      palpitations. She had recently been diagnosed with a congenital ventricular
      septal defect, bicuspid aortic valve, and Eisenmenger's syndrome. There was
      clinical evidence of right heart failure and differential clubbing and cyanosis
      affecting the feet but not hands. A cardiac magnetic resonance imaging
      demonstrated interruption of the aortic arch beyond the left subclavian artery,
      with the descending aorta perfused entirely through a large patent ductus
      arteriosus. 

PMID- 24124699
TI  - Identification of sociodemographic and clinical factors associated with the
      levels of human beta-defensin-1 and human beta-defensin-2 in the human milk of
      Han Chinese.
AB  - Human milk provides infants with various immune molecules. The objective of the
      present study was to measure human beta-defensin-1 (hBD-1) and human beta
      defensin-2 (hBD-2) levels in the colostrum and mature milk of healthy Han
      Chinese, to identify factors regulating milk hBD-1 and hBD-2 expression and to
      explore the potential protective effect of milk hBD-1 and hBD-2 on infants. A
      total of 100 mothers and their babies were recruited into the study.
      Sociodemographic characteristics and other factors were obtained by a
      questionnaire. Babies were followed up for a period of 6 months. Colostrum
      samples (n 100) and mature milk samples (n 82) were collected by hand expression.
      The hBD-1 and hBD-2 concentrations were measured by ELISA. The hBD-1 and hBD-2
      levels differed in the colostrum and mature milk. In the colostrum, the
      concentration ranges of hBD-1 and hBD-2 were 1.04-12.81 MUg/ml and 0.31-19.12
      ng/ml, respectively. In mature milk, the hBD-1 and hBD-2 levels were 1.03-31.76
      ng/ml and 52.65-182.29 pg/ml, respectively. Several independent factors influence
      their production. The multivariable analysis showed a strong association between
      pre-pregnancy BMI and hBD-1 levels in the colostrum (P=0.001), mode of delivery
      was significantly associated with hBD-2 levels in the colostrum (P=0.006) and
      gestational age was significantly associated with hBD-1 levels in mature milk (P=
      0.010). During the first 6 months of life, the incidence rate of upper
      respiratory infection was found to be less in the high-colostrum hBD-1 group than
      in the low-colostrum hBD-1 group (chi2=4.995, P=0.025). The present study
      suggested that the abundance of hBD-1 in the colostrum may have a protective
      function against upper respiratory infection for infants younger than 6 months.

PMID- 24124701
TI  - Endoscopy and esophageal pH study. Foreword.

PMID- 24124700
TI  - "This bicycle gives me a headache", a congenital anomaly.
AB  - BACKGROUND: [corrected] The combination of a presacral mass, a sacral bone
      deformity, and an anorectal malformation are also known as the Currarino triad or
      Currarino syndrome. The syndrome is associated with a very high rate of severe
      and intractable constipation and urinary incontinence. However, it can also
      result in less common complaints and symptoms. Although the syndrome is known
      since 1981 and the involved genes are clarified to a great extent, the diagnosis
      may be delayed or missed if unrecognized. CASE PRESENTATION: A 24-year old female
      presented with periodical headaches. She was born with an imperforate anus,
      absent rectum and colon, double bladder, and sacral defect. Soon after birth she
      underwent several surgical procedures for anorectal and bladder reconstructions.
      The patient now came to her pediatric urologist for urinary incontinence and
      mentioned severe headaches on the side, particularly when riding a bike. Finally,
      she solved her headache problem by stopping to ride her bicycle.On physical
      examination no abnormalities were found except the ileostomy that was present
      ever since soon after birth and her urinary incontinence. Blood tests showed no
      abnormalities. Additional MRI showed a large and previously not known anterior
      meningocele at the level of the sacrum. Surgical treatment consisted of closure
      of the dura by posterior approach. CONCLUSION: In this case report we describe
      the late discovery with an atypical presentation of an anterior meningocele in a
      young adult with urinary incontinence, a sacral defect, an anorectal malformation
      and headaches during bicycle riding. After surgical treatment of our patient the
      meningocele regressed. Three months after successful surgery she had no
      complaints and was able to ride a bike again.

PMID- 24124702
TI  - Common gastrointestinal symptoms: dysphagia.
AB  - Swallowing occurs in 3 phases: oral, pharyngeal, and esophageal. Oropharyngeal
      dysphagia typically is a result of neuromuscular disorders, such as stroke and
      parkinsonism, or of mucosal dryness caused by drugs or radiation therapy.
      Esophageal dysphagia is commonly caused by anatomic defects of the esophagus,
      such as reflux disease; motility disorders, such as achalasia; or eosinophilic
      esophagitis. If oropharyngeal dysphagia is suspected, the patient should undergo
      initial testing with a water or semisolid bolus swallow test. If results are
      positive, the diagnosis can be confirmed with a videofluoroscopic swallowing
      study. If esophageal dysphagia is suspected, patients typically undergo
      endoscopic esophagogastroduodenoscopy. Management of confirmed oropharyngeal
      dysphagia involves short-term compensation strategies, such as postural changes
      or food thickening, to minimize the risk of aspiration. This is followed by
      rehabilitation that may involve swallowing exercises with biofeedback or
      electrical stimulation of the swallowing muscles. Some patients may need enteral
      feeding. For esophageal dysphagia, choice of management depends on the etiology;
      it may include endoscopic dilation, myotomy, injection of onabotulinumtoxinA
      (formerly called botulinum toxin type A) for structural abnormalities, or topical
      steroid therapy for eosinophilic esophagitis. 

PMID- 24124703
TI  - Common gastrointestinal symptoms: irritable bowel syndrome.
AB  - The diagnosis of irritable bowel syndrome (IBS) should be considered when
      patients have had abdominal pain/discomfort, bloating, and change in bowel habits
      for 6 months. Patients may experience variation between periods of constipation
      and diarrhea. When evaluating patients with IBS, physicians should be alert for
      red flag symptoms, such as rectal bleeding, anemia, nighttime pain, and weight
      loss. Physicians also should consider other medical conditions that manifest
      similarly to IBS. Clinicians who are confident in diagnosing IBS based on
      symptoms typically do not obtain many tests unless the patient has red flag
      symptoms. Various etiologic mechanisms have been proposed for IBS, including
      abnormal bowel motility, inflammation, altered mucosal permeability, genetic
      predisposition, and visceral hypersensitivity. Lack of certainty about the
      etiology makes it difficult to develop effective management approaches; thus,
      management is directed toward symptom relief. Dietary changes, such as avoiding
      fermentable carbohydrates, may benefit some patients, especially those with
      bloating. Constipation-dominant IBS can be managed with antispasmodics,
      lubiprostone, or linaclotide, whereas diarrhea-dominant IBS can be managed with
      loperamide or alosetron, though the latter drug can cause ischemic colitis. For
      long-term therapy, tricyclic antidepressants or selective serotonin reuptake
      inhibitors have good efficacy. Peppermint oil and probiotics also may provide
      benefit. 

PMID- 24124704
TI  - Common Gastrointestinal Symptoms: dyspepsia and Helicobacter pylori.
AB  - The most common diagnoses among patients with dyspepsia are functional dyspepsia,
      gastroesophageal reflux disease, peptic ulcer, and gastric or esophageal cancer.
      Helicobacter pylori infection is present in many patients with dyspepsia and is
      etiologic in some conditions. The evaluation of dyspepsia divides patients into 3
      categories: 1) for patients taking nonsteroidal anti-inflammatory drugs (NSAIDs),
      NSAIDs should be discontinued; if symptoms resolve after discontinuation, no
      further evaluation is needed; 2) for patients with reflux symptoms, proton pump
      inhibitors (PPIs) should be prescribed without endoscopy unless alarm symptoms
      are present; and 3) for patients with no NSAID use or reflux symptoms, evaluation
      depends on risk. Patients older than 55 years or with alarm symptoms are at high
      risk and should undergo endoscopy. Those 55 years or younger with no alarm
      symptoms are at low risk. Those patients should be tested for H pylori and
      treated if results are positive. If symptoms persist after eradication treatment,
      PPIs should be prescribed for 4 to 6 weeks; if symptoms persist after treatment,
      endoscopy should be obtained. If H pylori test results are negative, PPIs should
      be prescribed for 4 to 6 weeks. Endoscopy should be obtained if symptoms persist.
      There are several regimens for eradication of H pylori. The most effective is
      sequential therapy with a PPI and amoxicillin for 5 days followed by a PPI,
      clarithromycin, and tinidazole for another 5 days. 

PMID- 24124705
TI  - Common gastrointestinal symptoms: risks of long-term proton pump inhibitor
      therapy.
AB  - More than 11 million individuals receive proton pump inhibitor (PPI)
      prescriptions each year in the United States. Although PPIs are effective
      treatment for peptic ulcers and esophagitis and provide symptom relief for many
      other conditions, their use carries risks. They decrease gastric acid and can
      lower blood levels of drugs whose absorption is acid dependent, including several
      antiretroviral and cancer therapy drugs. Other drugs, such as digoxin, may be
      absorbed more extensively when gastric acid is reduced; thus, digoxin toxicity
      may occur with PPI use. Warfarin's effect also is increased in patients taking
      PPIs. Decreased gastric acid can lower absorption of vitamin B12, calcium, iron,
      and magnesium; deficiencies in these nutrients are a concern. Several medical
      conditions, including Clostridium difficile infection, osteoporotic fractures,
      and community-acquired pneumonia, are more likely to occur among PPI users.
      Interstitial nephritis also has been reported. Because of these risks, clinicians
      should try to use the lowest possible dose of PPI and to discontinue PPI therapy
      if it is not essential. Step-down regimens can be used to decrease/discontinue
      treatment; these regimens may prevent or minimize the rebound acid hypersecretion
      that can occur with abrupt discontinuation. For some patients, occasional
      treatment with intermittent or on-demand regimens may be sufficient to control
      symptoms. 

PMID- 24124706
TI  - [Future and current status of head trauma in China].

PMID- 24124707
TI  - [Strengthen cooperation and updating the concept to improve the standardized
      management of neurosurgical critical care patients -for the publishing of "The
      Experts Consensus for Critical Care Management of Neurosurgical Illness (2013)"].

PMID- 24124708
TI  - [Role of small-dose recombinant human coagulation factor VIIa for coagulopathy in
      patients with isolated traumatic brain injury].
AB  - OBJECTIVE: To explore the role of small-dose recombinant human coagulation factor
      VIIa (rFVIIa) for coagulopathy in patients with isolated traumatic brain injury.
      METHODS: A total of 86 isolated traumatic brain patients with coagulopathy were
      treated at our neurosurgery intensive care unit (NICU) from January 2010 to
      December 2012. Their trauma registry data included mortality, pre-and post-rFVIIa
      coagulation parameters. Two-tailed paired t-test was used to determine
      significant changes in coagulation parameters and other major clinical
      parameters. RESULTS: Twenty-seven patients made up the low-dose rFVIIa (20 ug/kg)
      group. And the control group had 59 well-matched subjects. At admission, age,
      blood pressure, Glasgow coma scale score, hemoglobin, platelets and international
      normalize ratio were similar in both groups. After treatment, the INR of patients
      on rFVIIa was lower than that of the conventional treatment group (1.1 +/- 0.2 vs
      1.2 +/- 0.2, P < 0.01) and it declined more in the rFVIIa group (0.3 +/- 0.2 vs
      0.1 +/- 0.4, P = 0.05). No significant difference existed in mortality or length
      of stay between two groups.There was no occurrence of subsequent thromboembolic
      events. CONCLUSION: The application of small-dose rFVIIa can effectively reduce
      the value of INR and improve the coagulation status of patients. During the
      course of treatment, no major adverse events occur.

PMID- 24124709
TI  - [Guiding value of brain tissue oxygenation plus intracranial pressure monitoring
      in severe traumatic brain injury patients].
AB  - OBJECTIVE: To elucidate the effectiveness of brain tissue oxygenation (PbtO2)
      plus intracranial pressure (ICP) monitoring and targeted therapy in patients of
      severe traumatic brain injury (TBI). METHODS: A total of 46 patients with severe
      TBI (Glasgow coma scale, GCS scale <= 8) admitted at Jiangyin People's Hospital
      from June 2009 to June 2012 were divided randomly into 2 groups and evaluated
      prospectively.Patients undergoing ICP plus PbtO2 monitoring were compared with
      controls with ICP monitoring alone.Therapies of both patient groups were
      attempted to maintain an ICP < 20 mm Hg and a cerebral perfusion pressure (CPP)
      >= 60 mm Hg.Among those with PbtO2 monitoring, oxygenation was maintained at a
      level of >= 20 mm Hg.The scores of Glasgow outcome scale (GOS) were compared
      between two groups at Month 6 post-injury. RESULTS: The mean daily ICP and CPP
      levels were similar in each group.The mortality rate was 21.7% in patients with
      ICP monitoring alone and the favorable outcome rate was 47.8%.However, those
      receiving combined management had a significantly reduced mortality rate of 8.7%
      and good outcome rate of 65.2% (P < 0.05). CONCLUSION: The combined use of both
      ICP and PbtO2 may be associated with reduced mortality and improved outcome in
      patients with severe TBI.

PMID- 24124710
TI  - [Prognostic correlation of intracranial pressure monitoring in patients with
      severe craniocerebral injury].
AB  - OBJECTIVE: To explore the clinical application of intracranial pressure (ICP)
      monitoring and its prognostic correlation in patients with severe craniocerebral
      injury. METHODS: A total of 216 severe craniocerebral injury patients with scores
      of Glasgow coma scale 3-8 underwent craniotomy at Affiliated Qilu Hospital,
      Shandong University.And 168 cases of ICP monitoring were divided into 3 treatment
      groups and another 48 cases without ICP monitoring selected as the control
      group.According to ICP, stepwise treatment was administered to control the level
      of ICP and maintain the cerebral perfusion pressure to analyze the relationship
      between ICP monitoring and prognosis. RESULTS: As compared with the control
      group, there were significant decreases of disability and mortality rate for
      patients with ICP monitoring (A, B, C group). Especially group C had a better
      prognosis than the other groups for statistical significance.In addition, the
      dose and duration of mannitol of group A, B or C were significantly lower than
      those of the control group (P < 0.05). CONCLUSION: The application of ICP
      monitoring is capable of reducing mortality, improving prognosis and enhancing
      success rate of treating severe craniocerebral injury.

PMID- 24124711
TI  - [Operative strategies for bilateral brain contusion and laceration].
AB  - OBJECTIVE: To explore the operative strategies for bilateral brain contusion and
      laceration and evaluate their clinical significance. METHODS: Based on the
      clinical manifestations, computed tomography (CT) and intracranial pressure
      (ICP), different operative strategies were applied to 25 cases of bilateral brain
      contusion and laceration. The strategies were classified into 6 types according
      to the principles of decompression and brain protection.All cases received
      routine treatments at neurosurgical intensive care unit (ICU) ward. And the
      occurrences of operative complications and 6-month Glasgow outcome scale (GOS)
      were statistically analyzed. RESULTS: Type 1:4 cases of unilateral decompressive
      craniectomy without resection of contusion focus; Type 2:8 cases of unilateral
      decompressive craniectomy with resection of bilateral contusion focus; Type 3:5
      cases of bilateral decompressive craniectomy with resection of unilateral brain
      contusion; Type 4:5 cases of bilateral decompressive craniectomy; Type 5:1 case
      of bilateral brain contusion resection; Type 6:2 cases of bilateral decompressive
      craniectomy and brain contusion resection.Postoperative complications such as
      epilepsy, expanding contusion foci, brain infarction, encephalocele, incisional
      CSF leakage, intracranial infection, subdural hydroma and hydrocephalus were
      rare. The 6-month GOS revealed 6 cases of good outcome (n = 6), moderate
      disability (n = 8), severe disability (n = 3) and vegetative status (n = 5) and
      death (n = 3). CONCLUSION: Different operative strategies may be applied for
      severe brain contusion and laceration according to their clinical manifestations,
      CT findings and ICP values. And the efficacies are improved by operative
      strategies based on the principles of ICP control, prevention of secondary injury
      and brain function preservation.

PMID- 24124712
TI  - [Relationship between episodic memory and resting-state brain functional
      connectivity network in patients with Alzheimer's disease and mild cognition
      impairment].
AB  - OBJECTIVE: To explore the relationship between the scores of episodic memory (EM)
      encoding and retrieving and the resting-state changes of brain functional
      connectivity (FC) network of Alzheimer's disease (AD) and mild cognition
      impairment (MCI) patients. METHODS: All subjects were recruited from special care
      clinic and ward and health physical examination center, Qingdao Huanxiu Community
      and Affiliated Hospital, Medical College of Qingdao university from January 2009
      to July 2012.They were divided into AD group (n = 16), MCI group (n = 24) and
      normal control (NC) group (n = 24). The resting-state fMRI scans were performed
      with GE3.0T to acquire the blood oxygenation level dependent signals for EM
      encoding and retrieving. The two-sample t test was conducted between the groups
      and linear correlation analysis performed between EM and FC. RESULTS: Compared to
      the NC group, the AD and MCI groups exhibited decreased FC to posterior
      cingulated cortex (PCC) mainly in bilateral lateral temporal lobe, medial
      prefrontal cortex and right insula.Increased regions existed in posterior
      cerebellar lobe. Compared with the MCI group, the AD group showed decreased FC to
      PCC in medial prefrontal cortex, bilateral insulas, right inferior temporal gyrus
      and right fusiform gyrus.And increased regions lied in posterior cerebellar lobe,
      right occipital lobe and left superior parietal lobule. Compared with the NC
      group, the MCI group exhibited decreased FC to PCC in left lingualis gyrus, left
      frontal lobe, right middle temporal gyrus and corpus callosum.And increased
      regions lied in posterior cerebellar lobe.EM encoding scores (%) (AD group 34 +/-
      20, MCI group 47 +/- 17, NC group 69 +/- 15) were significantly different among
      three groups (P < 0.05).And retrieving scores (%) (AD group 31 +/- 18, MCI group
      57 +/- 22, NC group 81 +/- 16) were significantly different among three groups (P
      < 0.05). Altered functional connectivity regions of left triangle orbital
      inferior frontal gyrus (r = 0.642 98), left cuneus (r = 0.642 98) and left
      caudate nucleus (r = 0.642 68) showed positive correlations with the EM encoding
      scores in AD group (all P < 0.005). Other groups were not statistically
      significant. CONCLUSION: The resting-state FC networks of AD and MCI groups show
      significant differences. The MCI and AD patients have progressively decreased
      scores of episodic memory encoding and retrieving.And the declines of episodic
      memory encoding and partial regions of resting-state FC network are positively
      correlated in the AD group.

PMID- 24124713
TI  - [Surface electromyographic activities of submental muscles among stroke patients
      with dysphagia].
AB  - OBJECTIVE: To explore the swallowing functions of stroke patients with dysphagia.
      METHODS: A total of 41 subjects were recruited.There were 15 stroke patients with
      dysphagia, 12 stroke patients without swallowing disorders and 14 age-and gender
      matched healthy controls.Surface electromyography (sEMG) was employed over the
      suprahyoid muscle group.Single swallow was applied twice with 5 and 10 ml of thin
      liquid barium as well as 5 and 10 ml of paste barium.The duration, average
      amplitude of sEMG and peak amplitude of submental muscle contraction were
      compared among three groups.Three-way analysis of variance (ANOVA) was performed.
      RESULTS: No significant differences existed in the general data among three
      groups (P > 0.05).However, all volumes, consistencies and durations [ (1.38 +/-
      0.21), (1.66 +/- 0.30), (1.46 +/- 0.24), (1.78 +/- 0.28) s] were significantly
      longer for the group of dysphagia patients than for those without dysphagia and
      healthy subjects (P < 0.05).And the average amplitudes ( (16 +/- 6), (15 +/- 5),
      (20 +/- 13), (19 +/- 7) uV) were significantly smaller for the group of dysphagia
      patients than for those without dysphagia and healthy subjects (P < 0.05) while
      the peak amplitudes ((48 +/- 23), (51 +/- 23), (51 +/- 31), (63 +/- 32) uV) were
      significantly smaller for the group of dysphagia patients than for those without
      dysphagia and healthy subjects (P < 0.05). There were no significant differences
      between patients without dysphagia and those of healthy subjects (P > 0.05).
      CONCLUSION: As a simple and useful tool, sEMG is feasible for evaluating
      swallowing function and quantifying the strength of swallowing muscles in post
      stroke patients with dysphagia.

PMID- 24124714
TI  - [Retrospective and comparative analysis of therapy for degenerative chronic
      discogenic low back pain with end plate Modic changes with discography and
      intradiscal injection blockage].
AB  - OBJECTIVE: To evaluate the prognosticating effects of discography and intradiscal
      injection blockage for patients with degenerative chronic discogenic low back
      pain and end plate Modic changes when posterior lumbar interbody fusion (PLIF)
      was adopted. METHODS: Patients who received diagnostic discography for suspected
      degenerative discogenic low back pain were recruited. A total of 60 patients (42
      males and 18 females) with positive discography and end plate Modic changes at a
      single level were enrolled in the study and allocated into Groups A and B: Group
      A was both positive sign of discography and negative sign of intradiscal
      injection blockage two weeks later, which further was subdivided into Group A1
      (Modic I endplate change) and Group A2 (Modic II endplate change). Group B was
      both positive sign of discography and intradiscal injection blockage two weeks
      later, which further was subdivided into Group A1 (Modic I endplate change) and
      Group A2 (Modic II endplate change). There were 15 cases in each subgroup, with a
      mean age of 43.2 years old (29 to 62 years old). The lumbar decompression
      combined with interbody fusion was performed for these patients. The clinical
      outcome of each patient was evaluated and recorded by using the VAS and ODI
      before operation and at 24 months after the procedure. The bone fusion state was
      evaluated by both dynamic X-ray and CT reconstruction films. RESULTS: There was
      no statistical difference of the scales of VAS and ODI before operation.Compared
      with the scales before operation, although the scales of VAS and ODI of both
      group A and group B at 24 months after the procedure were significantly improved,
      the scales of both VAS and ODI of group B were significantly superior to group A.
      The statistics analysis showed that comparing the improvement rate of VAS and ODI
      before and after operation, group B was significantly superior to group A, but
      there was no obviously correlations between the type of Modic endplate change and
      the the improvement rate of VAS and ODI. CONCLUSION: The combination the
      discography with intradiscal injection blockage before operation would
      effectively prognosticate the therapy of posterior lumbar interbody fusion. There
      was no obviously correlations between the type of Modic endplate change and the
      improvement rate of VAS and ODI.

PMID- 24124715
TI  - [Evaluation of osteonecrosis of the femoral head treated with percutaneous
      retaining catheterization].
AB  - OBJECTIVE: To evaluate the efficacies of treating osteonecrosis of the femoral
      head (ONFH) with percutaneous retaining catheterization. METHODS: A total of 85
      patients (106 hips) of ONFH underwent percutaneous retaining catheterization with
      self-made instrument. There were stage I (n = 32, 40 hips), stage II (n = 41, 50
      hips), stage III (n = 7, 9 hips) and stage IV (n = 5, 7 hips) by Ficat and Arlet
      classification. The selection criteria include bone marrow edema (BME) of the
      femoral head and neck and joint fluid on magnetic resonance imaging (MRI).The
      percent method(%) of Orthopedics Branch of Association of Chinese Medical
      Association was used for evaluating the efficacies of ONFH with retained femoral
      head. A follow-up period of 2-10 years was conducted with plain radiograph.The
      standard was as follows: >90, excellent; 75-89, good; 60-74, passable; <60, bad.
      The combination of excellent and good denoted obvious effect rate; passable for
      valid rate; bad for invalid rate.The historical core decompression was used as
      control group.And chi(2) test was used for statistical analysis (P < 0.05).
      RESULTS: The obvious effect rate was 88%(35/40), 74%(37/50), 22%(2/9), 14%(1/7),
      the valid rate 7%(3/40), 12% (6/50) , 22% (2/9), 14%(1/7) and the invalid rate
      5%(2/40), 14% (7/50) , 56% (5/9), 72% (5/7) respectively in Ficat I, II, III and
      IV stage. No statistically significant differences existed between Ficat I and II
      stage (P > 0.05) .But there were statistically significant differences in other
      groups (P < 0.01) . CONCLUSION: Percutaneous retaining catheterization is
      efficaciously treating ONFH in Ficat I and II stage and it may also be used for
      ONFH in Ficat III and IV stage.

PMID- 24124716
TI  - [Effects of early goal-directed diuresis therapy on the outcomes of critical ill
      patients].
AB  - OBJECTIVE: To evaluate the effects of early goal-directed diuresis therapy on the
      outcomes of critical ill patients. METHODS: A total of 56 critical patients
      enrolled received an injection of furosemide 5-40 mg under a precondition of
      stable hemodynamics. They were divided into two groups:standard group [Central
      venous pressure (CVP) decreased below 8 mm Hg] (n = 30) and control group (if
      not) (n = 26) depending on the goal of CVP.And the differences of survival rate,
      intensive care unit (ICU) days and ventilation days after diuresis therapy were
      compared between two groups. RESULTS: The survival rate of standard group was
      significantly higher than that of control group (96.7% vs 84.6%, P < 0.05) while
      the ICU days (4.4 +/- 3.6 days) and ventilation days (1.2 +/- 1.1 days) after
      diuresis therapy of standard group were significantly shorter than that of
      control group (12.5 +/- 11.7 and 9.8 +/- 9.6 days, P < 0.05). CONCLUSION: Early
      goal-directed diuresis therapy can improve the prognosis of critical ill
      patients.

PMID- 24124717
TI  - [Clinical comparison of sevoflurane and propofol anesthesia with propofol and
      remifentanil anesthesia for children with cleft lip and palate repair surgery].
AB  - OBJECTIVE: To compare the clinical efficacies and safety of sevoflurane and
      propofol versus remifentanil and propofol anesthesia for children with cleft lip
      and palate repair surgery. METHODS: Upon the approval of hospital ethical
      committee,a total of 60 pediatric patients undergoing cleft lip and palate repair
      surgery were recruited from two hospitals between April 2011 and December 2012.
      All patients were randomly divided into 2 groups (n = 30 each). Group
      S:sevoflurane and propofol anesthesia; and group R: propofol and remifentanil
      anesthesia.Heart rate (HR), mean arterial pressure (MAP) and pulse oxygen
      saturation (SpO2) were recorded at the time before the induction (T0), after 2
      min of induction (T1), the beginning of surgery (T2) and the end of surgery
      (T3).Intubating satisfaction, time to extubation,incidence of emergence
      agitation, postoperative nausea and vomiting, and the complications of the airway
      were recorded. RESULTS: Satisfactory intubation rate was 90% in group S, versus
      83% in group R. And there was no significantly difference between the two group.
      There were no significantly difference between the two group with MAP and
      HR.Compared with T0, There were significantly difference with MAP and HR at T1,
      T2 in group R (P < 0.05). The incidence of emergence agitation was significantly
      higher in group S (7 cases) than that in group R (2 cases).there were no records
      of nausea, vomiting and laryngospasm. CONCLUSION: Under an adequate depth
      anesthesia, these two anesthesia techniques are safe for cleft lip and palate
      repair surgery, emergence agitation was high in sevoflurane anesthesia, propofol
      and remifentanil anesthesia provides lower heart rate.

PMID- 24124718
TI  - [Endovenous laser ablation versus conventional surgery for great saphenous
      varicose veins:meta-analysis of randomized trials].
AB  - OBJECTIVE: To review the available data of randomized controlled clinical trials
      (RCT) to compare endovenous laser therapy (EVLT) with conventional surgery of
      high ligation and stripping (HL/S) for the treatment of great saphenous varicose
      veins. METHODS: A systematic review of Pubmed, Cochrane Library, Embase, Web of
      Science, Ovid database, China National Knowledge Infrastructure (CNKI) database
      and Wanfang database was performed to retrieve RCT studies on the effectiveness
      of EVLT versus HL/S up to January 1999. The rates of postoperative recurrence at
      1 year, 2 years and major complications were analyzed by Review Manager 5.1
      software. RESULTS: Eight retrieved RCT studies and 1743 limps were evaluated. The
      ratios of recurrence were the same for EVLT and HL/S at 1 and 2 years post
      operation. For the ratios of major postoperative complications, there was no
      statistical difference between EVLT and HL/S in thrombosis, wound infection and
      phlebitis. But EVLT could reduce the ratio of paresthesia. CONCLUSIONS: Compared
      with HL/S, EVLT shows no significant difference in the 1/2-year recurrence rate
      or the rates of thrombosis, wound infection and phlebitis. However, it can
      decrease the rate of paresthesia.

PMID- 24124719
TI  - [Clinical characteristics and surgical treatment of distal posterior inferior
      cerebellar artery aneurysms].
AB  - OBJECTIVE: To summarize the clinical characteristics and surgical treatment of
      distal posterior inferior cerebellar artery (PICA) aneurysms. METHODS: Ten
      consecutive cases of distal PICA aneurysms at our institute were retrospectively
      reviewed from June 2005 to June 2010.Among them, there were 6 males and 4 females
      with a mean age of 39.1 (26-60) years.The clinical manifestations included
      intracranial hematoma (n = 9) and mass effect (n = 1). All patients had computed
      tomography (CT) and digital subtraction angiography (DSA) scans while some of
      them received computed tomographic angiography (CTA) or magnetic resonance
      imaging (MRI) examinations. All patients underwent microsurgical suboccipital
      craniotomy. RESULTS: DSA was the main diagnostic tool. Eight patients had their
      aneurysms at left side and 2 at right side.The locations were at second section
      (n = 2), third section (n = 2), forth section (n = 3) and fifth section (n =
      3).And 2 cases were associated with arteriovenous malformation at the same side.
      The diameters of aneurysms were 3-8.3 mm (<5 mm in 5, 5-10 mm in 5). The outcomes
      included clipping (n = 6), trapping (n = 3) and resection plus vessel anastomosis
      (n = 1). In all cases, treatment was successful without neurological deficits.One
      patient had postoperative complication of intracranial infection and 1 patient
      with hydrocephalus underwent ventricular-peritoneal shunt.All of them achieved
      excellent recovery. The mean follow-up period was 4.6 years (range:2-5). None of
      them suffered re-bleeding.And the mean modified Rankin scale scores was 4.9.
      CONCLUSION: Patients with distal PICA aneurysms may obtain excellent outcome
      after microsurgery.

PMID- 24124720
TI  - [Expression of serum microRNAs (miR-222, miR-181, miR-216) in human
      hepatocellular carcinoma and its clinical significance].
AB  - OBJECTIVE: To investigate the abnormal expression of microRNAs (miR-216, miR-222,
      miR-181) in the serum of patients with hepatocellular carcinoma (HCC) and its
      clinical significance. METHODS: Serum miRNAs expression was investigated in 49
      patients with HCC and 25 healthy normal controls by using real-time PCR
      technique, and then correlations between miRNAs expression and the
      clinicopathological features and prognosis of HCC patients were evaluated.
      RESULTS: No differences were observed between the HCC patients and healthy
      controls with respect to the expressions of serum miR-181 and miR-216 (P > 0.05),
      while miR-222 was found to be significantly overexpressed in HCC serum samples
      (6.1 +/- 6.6 vs 1.2 +/- 0.6, P < 0.01). According to the median fold change of
      miR-222 (3-fold) in all HCC serum samples, we divided the 49 patients into two
      groups:a low expression group (25 patients) and a high expression group (24
      patients).High level of miR-222 expression was correlated with cirrhosis (P <
      0.01), tumor number (P = 0.013), portal vein tumor thrombosis (P = 0.002) and TNM
      stage (P = 0.020), while not correlated with serum alpha-fetoprotein level, tumor
      size and HbsAg. Kaplan-Meier survival analysis showed that the median overall
      survival in the high miR-222 expression group was significantly shorter than that
      in the low expression group (8.7 months vs 16.5 months, P = 0.036). In
      multivariate Cox analysis, TNM stage and serum miR-222 expression were two
      independent prognostic factors. CONCLUSION: Serum miR-222, upregulated in HCC,
      maybe helpful in prognosis of HCC patients.

PMID- 24124721
TI  - [The application value of BI-RADS lexicon and high-frequency CDFI scoring in
      differentiation of benign from malignant lesions of the breast].
AB  - OBJECTIVE: To explore the diagnostic value with BI-RADS lexicon and high
      frequency color doppler ultrasonic scoring for breast diseases. METHODS: A total
      of 108 breast lesions were studied with BI-RADS lexicon and high-frequency color
      doppler ultrasonic scoring, and compared with pathologic results. Calculated the
      sensitivity, specificity, accuracy, positive predictive value, and negative
      predictive value. RESULTS: Of these 108 lesions, 65(60.19%) were pathologically
      confirmed to be benign and 43(39.82%) to be malignant. There were no
      statistically significant differences between BI-RADS lexicon and high-frequency
      color doppler ultrasonic scoring in the diagnosis of breast lesions (P > 0.05).
      CONCLUSION: Both of BI- RADS lexicon and high-frequency color doppler ultrasonic
      scoring have a higher value for diagnosing breast disease in clinical
      application, and BI-RADS lexicon provides the normalized and standardized
      reporting data for clinical doctor in diagnosing breast disease, It is more
      conducive to guide clinicians with correct judgment and active treatment for
      breast disease.

PMID- 24124722
TI  - [Video-assisted thoracoscopic surgery bronchial sleeve lobectomy for lung
      cancer].
AB  - OBJECTIVE: To discuss the feasibility of video-assisted thoracoscopic
      surgery(VATS) bronchial sleeve lobectomy for NSCLC,and to describe this treatment
      method and the major Indications. METHOD: Between September 2010 and December
      2012, 10 patients in our hospital underwent VATS bronchial sleeve lobectomy.The
      patients were one female and nine males.Included 3 cases on the right upper lobe,
      3 cases on the right lower lobe, 1 case on the right middle lobe, 2 cases on the
      left upper lobe, 1 case on the left lower lobe.2 cases underwent VATS bronchial
      sleeve lobectomy and sleeve resection of the pulmonary artery. RESULTS: 10 cases
      were finished by Video-Assisted Thoracoscopic Surgery.They all recovered well.No
      patient showed bronchopleural fistula, empyema and atelectasis.There was no
      perioperative death. CONCLUSIONS: Video-assisted thoracoscopic surgery (VATS)
      lobectomy including bronchial sleeve lobectomy is therefore considered to be a
      feasible surgical modality for the treatment of patients with NSCLC.

PMID- 24124723
TI  - [Combined inflating lung and insufflating calf pulmonary surfactant under general
      anesthesia in the treatment of postoperative intractable atelectasis].
AB  - OBJECTIVE: To explore the efficacy and safety of combined inflating lung and
      insufflating calf pulmonary surfactant under general anesthesia for treating
      postoperative intractable atelectasis. METHODS: From August 2006 to January 2013,
      15 patients with obstinate postoperative atelectasis receiving pressure control
      lung expansion were enrolled. The bronchial cannula was intubated into the
      affected side to assist the expanding of the lung, and the calf pulmonary
      surfactant was insufflated selectively. The chest auscultation and computed
      tomography (CT) scan was performed at 1 d and 5 d after the procedure
      respectively, to evaluation the effect. The airway pressure, mean arterial
      pressure (MAP), heart rate (HR), respiratory rate (RR) and oxygen saturation
      (SpO2) were recorded before the treatment, during the treatment and after the
      treatment.Monitoring arterial blood gas before and after treatment. RESULTS:
      After the expansion of the lung and insufflation of calf pulmonary surfactants,
      the iconographic scan showed that collapsed alveolar was reinflated in 12 (80.0%)
      patients at 1 d after the treatment and in 14 patients(93.3%) at 5 d after the
      procedure.There were not notable vital sign change and complications during the
      treatment.At after the treatment, 1, 3, 5 and 7 d after the treatment, PaO2 was
      higher (P < 0.05), and there were not significantly difference in the PaCO2 and
      pH (P > 0.05) . CONCLUSION: Combined pressure control lung expansion with
      selectively insufflating calf pulmonary surfactant under general anesthesia may
      be an effective therapy for postoperative intractable atelectasis.

PMID- 24124724
TI  - [Treatment of degenerative lumbar scoliosis with selective segmental
      transforaminal lumbar interbody fusion].
AB  - OBJECTIVE: To explore the treatment outcomes of degenerative lumbar scoliosis
      (DLS) with selective segmental transforaminal lumbar interbody fusion (TLIF).
      METHODS: The clinical data were analyzed for a total of 42 cases with
      degenerative scoliosis from November 2008 to March 2011.There were 14 males and
      28 females with a mean age of 62.4 years (range, 41-76).The indications for TLIF
      of motion segment included segmental instability and significant upper endplate
      obliquities of L3 or L4.Interbody spinal fusion was performed for 3 segments in 3
      cases; 2 in 17; 1 in 22.All patients were followed postoperatively with a mean
      duration of 1.6 years (range, 0.5-3).The imaging examinations included Cobb angle
      of scoliosis and lumbar lordosis angle.The clinical symptoms were evaluated with
      Oswestry disability index (ODI) score. RESULTS: The mean preoperative Cobb angle
      of 32.7 degrees  +/- 12.4 degrees  was significantly corrected to 9.2 degrees  +/
      5.5 degrees  at the final follow-up (t = 14.86, P < 0.05) with a correction rate
      of 71.8%. The mean preoperative lumbar lordosis angle of 25.5 degrees  +/- 12.6
      degrees  was also significantly corrected to 39.3 degrees  +/- 8.5 degrees  (t =
      12.11, P < 0.05) with a correction rate of 46.4%.There was significant difference
      (P < 0.05) in ODI between preoperation (43.8 +/- 5.6) and postoperation (18.7 +/-
      1.8).But no significant difference (P > 0.05) existed in ODI between
      postoperation (18.7 +/- 1.8) and the final follow-up (23.6 +/- 2.3). And 86% of
      the patients showed considerable symptomatic improvement of neurogenic
      intermittent claudication. And clinical symptoms and functional tolerance for
      daily activities improved postoperatively in 92%. At the follow-up after 6 months
      postoperatively, all operated segments achieved fusion standard and no
      pseudoarthrosis formed. CONCLUSION: Selective segmental TLIF is helpful in
      correcting lumbar lordosis, segmental deformity and translation. And it offers
      better outcomes of posterior spinal fusion for the treatment of DLS.

PMID- 24124725
TI  - [Detection of protein secretion and expression and osteogenic activity of adipose
      tissue-derived stem cells after in vitro transfection of vascular endothelial
      growth factor].
AB  - OBJECTIVE: To examine vascular endothelial growth factor (VEGF) protein secretion
      and expression and explore the osteogenic activity of adipose tissue-derived stem
      cells (ADSCs) after transfection of human VEGF. METHODS: The ADSCs were isolated
      from human adipose tissue after the digestion of collagenase.After identification
      by flow cytometry, the cells were cultured and passaged in nutritive medium. Gene
      sequence encoding human VEGF mature peptide was obtained by Trizol reagent method
      from human vascular tissue. Target gene VEGF was connected with bicistronic
      expression vector containing green fluorescent protein to form pSELECT-GFP zeo
      VEGF for transfecting 2nd, 3rd, 4th, 5th generation ADSCs mediated by liposome.
      The transfection results were verified under fluorescence microscope. VEGF
      protein secretion by transfected cells was detected by enzyme-linked
      immunosorbent assay (ELISA). Second-generation transfected ADSCs were cultured
      under osteogenic conditions.The supernatant levels of alkaline phosphatase (ALP)
      and osteocalcin (OC) were detected. RESULTS: Liposome-mediated VEGF target gene
      fragment could transfect ADSCs successfully. ELISA quantitative detection showed
      that VEGF mRNA expression levels in supernatant of the transfected group was
      significantly higher than the control group. And there were significant
      differences. After osteogenic culturing, the detections of ELISA, real-time PCR
      and Western blot showed that the secretion of ALP and OC of VEGF transfected
      group was significantly higher than that of empty vector transfected and blank
      cell groups.And there were significant differences (P < 0.01). CONCLUSION: After
      transfected by liposome-mediated VEGF target gene fragment, human ADSCs can
      express biologically active VEGF mRNA in vitro continuously and effectively.
      Directional differentiation capacity of transfected ADSCs is significantly
      enhanced.

PMID- 24124727
TI  - Transgastric migration of gossypiboma remedied with endoscopic removal: a case
      report.
AB  - BACKGROUND: Retained surgical instrument or sponge following an intra-abdominal
      surgery is a potentially dangerous medico-legal problem. The condition may
      manifest either as asymptomatic or severe gastrointestinal complications.
      Transmural migration of gossypiboma is a rare entity that may lead to bowel or
      visceral perforation, obstruction and/or fistula formation. Transmural migration
      of an intra-abdominal gossypiboma has been reported to occur in stomach, ileum,
      colon, bladder, vagina and diaphragm. To our knowledge, this is the fifth case
      reported in the medical literature. However, we report the first case of the
      largest gossypiboma to date: a surgical gas compress measuring 20 * 20 cm which
      was successfully treated endoscopically. CASE PRESENTATION: A 52-year-old woman
      with obstructive jaundice was referred to our clinic. She had a medical history
      of cholecystectomy and T-tube drainage for choledocholithiasis a year previously.
      Abdominal ultrasonography and computed tomography revealed a mass located into
      the stomach which was compatible with gastric carcinoma. On the gastroscopy, a
      surgical gas compress that had totally migrated into the stomach was observed.
      The compress was successfully removed by gastroscopy through the esophagus. The
      recovery of the patient was uneventful. CONCLUSION: Transmural migration of
      gossypiboma into the stomach should be considered in the differential diagnosis
      of any postoperative patient with obstructive jaundice symptoms. Endoscopy may be
      feasible for both diagnosis and treatment even though the size of gossypiboma is
      large. However, surgery should be considered in case of fixed reaction or
      incomplete migration of gossypiboma located into the stomach.

PMID- 24124726
TI  - Antitumor efficacy of a recombinant adenovirus encoding endostatin combined with
      an E1B55KD-deficient adenovirus in gastric cancer cells.
AB  - BACKGROUND: Gene therapy using a recombinant adenovirus (Ad) encoding secretory
      human endostatin (Ad-Endo) has been demonstrated to be a promising
      antiangiogenesis and antitumor strategy of in animal models and clinical trials.
      The E1B55KD-deficient Ad dl1520 was also found to replicate selectively in and
      destroy cancer cells. In this study, we aimed to investigate the antitumor
      effects of antiangiogenic agent Ad-Endo combined with the oncolytic Ad dl1520 on
      gastric cancer (GC) in vitro and in vivo and determine the mechanisms of these
      effects. METHODS: The Ad DNA copy number was determined by real-time PCR, and
      gene expression was assessed by ELISA, Western blotting or immunohistochemistry.
      The anti-proliferation effect (cytotoxicity) of Ad was assessed using the
      colorimetry-based MTT cell viability assay. The antitumor effects were evaluated
      in BALB/c nude mice carrying SGC-7901 GC xenografts. The microvessel density and
      Ad replication in tumor tissue were evaluated by checking the expression of CD34
      and hexon proteins, respectively. RESULTS: dl1520 replicated selectively in GC
      cells harboring an abnormal p53 pathway, including p53 mutation and the loss of
      p14(ARF) expression, but did not in normal epithelial cells. In cultured GC
      cells, dl1520 rescued Ad-Endo replication, and dramatically promoted endostatin
      expression by Ad-Endo in a dose- and time-dependent manner. In turn, the addition
      of Ad-Endo enhanced the inhibitory effect of dl1520 on the proliferation of GC
      cells. The transgenic expression of Ad5 E1A and E1B19K simulated the rescue
      effect of dl1520 supporting Ad-Endo replication in GC cells. In the nude mouse
      xenograft model, the combined treatment with dl1520 and Ad-Endo significantly
      inhibited tumor angiogenesis and the growth of GC xenografts through the
      increased endostatin expression and oncolytic effects. CONCLUSIONS: Ad-Endo
      combined with dl1520 has more antitumor efficacy against GC than Ad-Endo or
      dl1520 alone. These findings indicate that the combination of Ad-mediated
      antiangiogenic gene therapy and oncolytic Ad therapeutics could be one of
      promising comprehensive treatment strategies for GC.

PMID- 24124729
TI  - Holt-Oram syndrome with aortopulmonary window--a rare association.
AB  - A 4-month-old male infant presented with recurrent cough for 2 months. He had a
      shortened right upper limb with absent right thumb and continuous murmur in the
      left parasternal area. The X-ray showed an absent radius and the first metacarpal
      and phalyngeal bones on the right side. Echocardiogram revealed aortopulmonary
      window and small secundum atrial septal defect. Aortopulmonary window was
      successfully treated by device closure. Holt-Oram syndrome with aortopulmonary
      window is an extremely rare association. 

PMID- 24124728
TI  - Antibiotic resistance among Escherichia coli isolates from stool samples of
      children aged 3 to 14 years from Ujjain, India.
AB  - BACKGROUND: Antibiotic resistance is a major global public health concern,
      particularly in settings where few treatment options are available. Limited
      research has been done on antibiotic resistance in Escherichia coli of Indian
      children at community level. Therefore we studied antibiotic resistance patterns
      in E. coli isolates from stool samples of children aged 3-14 years from Ujjain,
      Central India, to investigate associations of resistance with demographic
      variables. METHODS: Children, 3-14 years of age, were included from 30 randomly
      selected villages of Palwa demographic surveillance site, Ujjain, India. Parents
      were interviewed using a questionnaire, and stool samples were collected from
      participating children. E. coli were isolated from stool samples (n = 529), and
      susceptibility testing to 18 different antibiotics was done using standard
      methods. RESULTS: The proportions of isolates resistant to various antibiotics
      were, nalidixic acid, (45%), tetracycline (37%), ampicillin (37%),
      sulfamethoxazole/trimethoprim (29%) and amoxicillin/clavulanic acid (29%). No
      isolates were resistant to imipenem. Overall, 72% of isolates were resistant to
      at least one antibiotic and 33% were multi-drug resistant. High rates of cross
      resistance were seen for 15 (83%) of the antibiotics studied. E. coli isolates
      from children with literate mothers were more resistant to penicillins and
      fluoroquinolones. ESBL-producers comprised 9% of the isolates. CONCLUSION:
      Antibiotic resistance and cross-resistance were common in E. coli from stools of
      children. Resistance rates were associated with maternal literacy.

PMID- 24124730
TI  - Effect of feeding goats with distilled and non-distilled thyme leaves (Thymus
      zygis subp. gracilis) on milk and cheese properties.
AB  - The aim of this study was to evaluate the effect of feeding goats with distilled
      and non-distilled thyme leaves (Thymus zygis subsp. gracilis) on the
      physicochemical composition and technological properties of pasteurised goat
      milk, and on the physicochemical composition, phenolic content, oxidative
      stability, microbiology, sensory and texture profile of Murcia al Vino goat
      cheese. One group of goats was fed the basal diet (control), the second and third
      groups were fed with different levels of distilled (10 and 20%) or non-distilled
      (3.75 and 7.5%) thyme leaves. Goat milk physicochemical composition was
      significantly affected by the substitution of 7.5% of basal goat diet with non
      distilled thyme leaves (increase in fat, protein, dry matter and PUFA content),
      while goat milk clotting time was increased significantly by the introduction of
      20% distilled thyme leaves, which reduces its technological suitability.
      Microbiology, sensory and texture profiles were not affected by the introduction
      of distilled thyme leaves. The introduction of distilled and non-distilled thyme
      leaves as an alternative feed to diet can lead to an inhibition of lipids
      oxidation. The introduction of distilled and non-distilled thyme leaves into
      goat's diet can be successfully adopted as a strategy to reduce feeding costs and
      to take advantage of the waste from the production of essential oils, minimising
      waste removing costs and the environmental impact. 

PMID- 24124733
TI  - [Focus on the prevention, treatment and management of venous thromboembolism:
      what can we learn from the 9th ACCP guidelines].

PMID- 24124732
TI  - Myocardial T1 mapping and extracellular volume quantification: a Society for
      Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European
      Society of Cardiology consensus statement.
AB  - Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the
      routine acquisition of quantitative measures of myocardial and blood T1 which are
      key tissue characteristics. These capabilities introduce a new frontier in
      cardiology, enabling the practitioner/investigator to quantify biologically
      important myocardial properties that otherwise can be difficult to ascertain
      clinically. CMR may be able to track biologically important changes in the
      myocardium by: a) native T1 that reflects myocardial disease involving the
      myocyte and interstitium without use of gadolinium based contrast agents (GBCA),
      or b) the extracellular volume fraction (ECV)-a direct GBCA-based measurement of
      the size of the extracellular space, reflecting interstitial disease. The latter
      technique attempts to dichotomize the myocardium into its cellular and
      interstitial components with estimates expressed as volume fractions. This
      document provides recommendations for clinical and research T1 and ECV
      measurement, based on published evidence when available and expert consensus when
      not. We address site preparation, scan type, scan planning and acquisition,
      quality control, visualisation and analysis, technical development. We also
      address controversies in the field. While ECV and native T1 mapping appear
      destined to affect clinical decision making, they lack multi-centre application
      and face significant challenges, which demand a community-wide approach among
      stakeholders. At present, ECV and native T1 mapping appear sufficiently robust
      for many diseases; yet more research is required before a large-scale application
      for clinical decision-making can be recommended. 

PMID- 24124734
TI  - [Dynamic changes of inflammation-related indices in venous thromboembolism and
      the association between these indices and venous thromboembolism].
AB  - OBJECTIVE: To evaluate the dynamic changes of inflammation-related indices in
      blood during the development of venous thromboembolism (VTE) and the association
      between these indices and VTE. METHODS: A total of 95 VTE hospitalized
      patients(41 males,54 females) were recruited from Department of Respiratory and
      Critical Care Medicine, Beijing Chaoyang Hospital from January 2010 to December
      2010. Comparisons of inflammation-related indices including white blood cell
      (WBC), neutrophil (NE), fibrinogen (FBG), C-reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR) were conducted between VTE patients and
      normal ranges. And the dynamic changes of these indices during the development of
      VTE were evaluated. Then they were divided into subgroups according to disease
      stage, gender, age, VTE type, body mass index, smoking status and clinical
      manifestations. And statistical analyses were performed to elucidate the
      associations between these indices and VTE. RESULTS: The levels of NE and CRP in
      VTE patients (0.72, 15.0 mg/L) and ESR in male VTE patients (20.0 mm/1 h) were
      elevated compared with normal ranges; while WBC (male 7.27*10(9)/L, female
      8.67*10(9)/L), FBG (male 3621 mg/L, female 3201 mg/L) and female ESR (19.5 mm/1
      h) in VTE patients were within the normal ranges. The level of CRP was higher in
      acute (mean rank order value: 49.72) and sub-acute (mean rank order value: 44.80)
      VTE patients than chronic VTE patients (mean rank order value: 30.25). The level
      of FBG, CRP and ESR in patients >= 50 years old increased versus those <50 years
      old (mean rank order values 48.83 vs 34.53, 44.32 vs 28.90 and 45.95 vs 27.84
      respectively), the patients whose body mass index (BMI) <25 kg/m(2) had higher
      WBC level than those whose BMI >= 25 kg/m(2) (mean rank order values 52.96 vs
      36.46); smoking VTE patients had elevated FBG and CRP levels than non-smoking VTE
      patients (mean rank order values 57.75 vs 42.69 and 53.92 vs 37.75 respectively);
      compared with those without clinical manifestations of periphery pulmonary artery
      involved, the patients with clinical manifestations had higher levels of FBG, CRP
      and ESR (mean rank order values 59.24 vs 37.39, 52.68 vs 33.19 and 50.08 vs 36.55
      respectively). The above differences had statistical significance (all P < 0.05).
      CONCLUSIONS: Some inflammation-related indices frequently used in clinical
      settings become elevated in VTE patients. Part of these indices show higher
      levels in VTE acute and sub-acute stages, and in older, non-obese, smoking and
      periphery pulmonary artery involved VTE patients.

PMID- 24124731
TI  - Hematopoietic stem cell injury induced by ionizing radiation.
AB  - SIGNIFICANCE: Exposure to ionizing radiation (IR) as the result of nuclear
      accidents or terrorist attacks is a significant threat and a major medical
      concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after
      accidental or intentional exposure to a moderate or high dose of IR. Protecting
      HSCs from IR should be a primary goal in the development of novel medical
      countermeasures against radiation. RECENT ADVANCES: Significant progress has been
      made in our understanding of the mechanisms by which IR causes HSC damage. The
      mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii)
      promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF
      dependent differentiation checkpoint; (iii) induction of HSC senescence via the
      ROS-p38 pathway; and (iv) damage to the HSC niche. CRITICAL ISSUES: Induction of
      apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for
      IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR
      is mainly attributable to the induction of HSC senescence. However, the promotion
      of HSC differentiation and damage to the HSC niche can contribute to both the
      acute and long-term effects of IR on the hematopoietic system. FUTURE DIRECTIONS:
      In this review, we have summarized a number of recent findings that provide new
      insights into the mechanisms whereby IR damages HSCs. These findings will provide
      new opportunities for developing a mechanism-based strategy to prevent and/or
      mitigate IR-induced BM suppression. Antioxid.

PMID- 24124735
TI  - [Validity of Caprini risk assessment model in identifying high venous
      thromboembolism risk patients among hospitalized medical patients].
AB  - OBJECTIVE: To test the validity of Caprini risk assessment model in identifying
      high venous thromboembolism (VTE) risk patients among hospitalized medical
      patients. METHODS: A retrospective case-control study was performed among
      hospitalized medical patients admitted into West China Hospital, Sichuan
      University from January 2010 and December 2011. A total of 218 patients with
      definite VTE during hospitalization were recruited. And 394 controls were
      randomly selected from the patients without VTE admitted into the same
      departments within the same period. The risks of both cases and controls were
      retrospectively assessed with the Caprini risk assessment model. RESULTS: The
      average Caprini cumulative risk score in cases was significant higher than that
      in controls (4.9 +/- 2.6 vs 3.2 +/- 2.0, P = 0.000). There was no significant
      difference in the risk of VTE between the patients at a low risk by Caprini model
      and those at a moderate risk (OR = 1.26, 95%CI: 0.62-2.56). Compared with a low
      risk, those with a high risk were associated with 2.00-fold increased risk of VTE
      (95%CI: 1.10-3.61), a highest risk was associated with 5.76-fold increased risk
      of VTE (95%CI: 3.24-10.24) (both P < 0.05) . When further stratifying the highest
      risk level with cumulative risk score >= 5 into 5-6, 7-8, and >= 9 risk level,
      the patients with score 5-6 were associated with 4.15-fold increased risk of VTE
      (95%CI: 2.28-7.56), those with score 7-8 11.13-fold increased risk of VTE (95%CI:
      4.88-25.36) and those with score >= 9 21.00-fold increased risk of VTE (95%CI:
      6.34-69.52) compared with low risk counterparts. CONCLUSION: Caprini risk
      assessment model can effectively and quantitatively assess the risk of VTE among
      hospitalized medical patients based on their individual VTE risk factors.

PMID- 24124736
TI  - [Incidence of pulmonary embolism in patients with acute exacerbations of chronic
      obstructive pulmonary disease: a meta-analysis].
AB  - OBJECTIVE: To evaluate the incidence of pulmonary embolism in patients with acute
      exacerbations of chronic obstructive pulmonary disease (COPD). METHODS:
      Comprehensive searches as of June 2012 were performed in PubMed (1966-), Embase
      (1974-), Chinese Biomedical Literature Database (1978-), Chinese Journal Full
      text Database (1979-) and VIP Database (1989-) for literatures on the incidence
      of pulmonary embolism in patients with acute exacerbations of COPD. Meta-analysis
      was conducted with Stata version 11.0. RESULTS: Among 2273 articles identified, 5
      studies met the inclusion criteria (4 in English, 1 in Chinese). The total sample
      size was 762 patients, among whom 145 were diagnosed with pulmonary embolism. The
      incidence of pulmonary embolism ranged from 3.3% to 33.0%. Meta-analysis showed
      that the combined incidence was 15.8% (95%CI: 5.1%-26.4%). Among patients with
      acute exacerbations of COPD of unknown etiology, the incidence was 29.0% (95%CI:
      20.8%-37.1%). CONCLUSIONS: There is a high incidence of pulmonary embolism in
      patients with acute exacerbations of COPD, especially among those of an unknown
      etiology. More attention should be paid to this population.

PMID- 24124737
TI  - [Analysis of clinical features among severe or critical pregnant women in
      different trimesters with 2009 pandemic H1N1 infection].
AB  - OBJECTIVE: To explore the disease course and outcomes of severe or critical
      pregnant women with 2009 pandemic H1N1 (pH1N1) infection in China. METHODS: A
      retrospective observational study was conducted for 394 severe or critical
      pregnant women with pH1N1 influenza admitted into hospital in 27 Chinese
      provinces from September 1, 2009 to December 31, 2009. Their clinical features in
      different trimesters were analyzed. The viral infection of pH1N1 was verified by
      real-time reverse transcription (rRT)-PCR. Severe and critical cases were defined
      according to the 2009 H1N1 clinical guidelines. RESULTS: Among them, 374 (94.9%)
      were infected in the second or third trimester. Fever and cough were the most
      common symptoms in all trimesters. However, hemoptysis, dyspnea and associated
      pneumonia were likely to occur in the second or third trimester. The ratio of
      required mechanical ventilation in the second or third trimester (44.7%, 167/374)
      was significantly higher than that in the first trimester (3/20). Among 77
      mortality cases, 72.7% (56/77) died in the third trimester. Pregnancy was
      terminated after the onset of pH1N1 symptoms in 52.5%(207/394) pregnant women.
      And 57.0%(118/207) of them had delivery < 37 weeks and 29.0%(60/207) fetuses
      deceased. CONCLUSION: A clinician should be on a high alert for pH1N1 infection
      in pregnant women, particularly in the second or third trimester.

PMID- 24124738
TI  - [Expression and promoter methylation of SIX2 gene in peripheral blood of
      pediatric patients with nephroblastoma].
AB  - OBJECTIVE: To explore the transcriptional expression and promoter methylation
      status of SIX2 gene in peripheral blood of pediatric children with nephroblastoma
      and discuss their clinicopathological correlations. METHODS: Approved by the
      hospital ethics committee, peripheral blood samples were collected from 45
      children with Wilms' tumor(case group) at the Department of Pediatric Surgery,
      First Affiliated Hospital, Zhengzhou University from October 2008 to January
      2012. And another 15 pediatric cases gender-and-age matched, were selected as the
      control group (excluding cancer and other malignant diseases). The real-time
      quantitative (qRT)-PCR and methylation-specific PCR (MSP) were used to detect the
      mRNA expression level and methylation status of SIX2 gene.t or chi(2) test were
      used. Then analyzed their clinicopathological correlations in the case group and
      how SIX2 gene methylation affected its transcription. RESULTS: Relative
      quantity(RQ) of SIX2 mRNA in the case group was higher than that of the control
      group (1.93 +/- 1.10 vs 0.57 +/- 0.39, t = 5.354, P = 0.000). There were 8 SIX2
      gene methylation-positive cases in the case group versus 12 cases in the control
      group. And the methylation positive ratio was extremely lower in the case group
      (chi(2) = 19.600, P = 0.000). RQ values in the case group was associated with
      tumor size, clinical stage, pathological type, lymph node metastasis, treatment
      and outcome (all P < 0.05). RQ values in the methylated group was lower than that
      of the unmethylated group both in case and control group (1.35 +/- 0.44 vs 1.95
      +/- 1.15, 0.43 +/- 0.29 vs 1.13 +/- 0.20, t = 2.459 and 3.896, P = 0.020 and
      0.002) . RQ values of case group was higher than that of the control group in
      methylated group (t = 5.624, P = 0.000) . No statistical significance existed in
      RQ values between the case and control groups of unmethylated group (t = 1.222, P
      = 0.229) . CONCLUSIONS: A close correlation between SIX2 low methylation and high
      mRNA expression in blood suggests that aberrant promoter methylation is possibly
      one of gene expression regulations, and may be correlated with the occurrence and
      development of Wilms' tumor. And SIX2 gene in methylated Wilms' tumor may play
      the role of oncogenes. A negative correlation exists between the overexpression
      in transcriptional level and its methylation status.

PMID- 24124739
TI  - [Altered patterns of functional connectivity of posterior cingulate cortex on
      resting-state magnetic resonance imaging in children with attention-deficit or
      hyperactivity disorder].
AB  - OBJECTIVE: To explore the pathophysiological changes in the functional
      connectivity of posterior cingulate cortex (PCC) with other brain regions in
      children with attention-deficit or hyperactivity disorder (ADHD) on resting-state
      functional magnetic resonance imaging(fMRI) and explore the neural mechanisms of
      ADHD at the point of relationships between brain regions. METHODS: Thirty
      children with ADHD from the Third Affiliated Hospital of Soochow University from
      June 2008 to April 2010 and another 30 age-and-gender-matched controls from a
      normal primary school over the same period underwent resting-state fMRI scans.
      And blood oxygenation level dependent (BOLD) signal was acquired to calculate the
      functional connectivity of PCC with other brain regions controls. Significant
      differences of connectivity between groups were analyzed with REST software.
      RESULTS: The pattern of functional connectivity of PCC for the ADHD group was
      similar to that of the control group. Significant positive functional
      connectivity with PCC was observed in the default mode of network (DMN) while
      negative functional connectivity was present in dorsolateral prefrontal cortex,
      anterior cingulate, parietal cortex and basal ganglia(all P < 0.05, corrected).
      Compared to the controls, the ADHD group exhibited decreased positive
      connectivity with PCC in bilateral medial prefrontal cortex (0.07 +/- 0.20 vs
      0.33 +/- 0.23, t = -5.47), right posterior cingulate gyrus(0.25 +/- 0.28 vs 0.48
      +/- 0.30, t = -3.44), right inferior temporal gyrus (-0.05 +/- 0.19 vs 0.22 +/-
      0.22, t = -4.61) and cerebellar posterior lobe (-0.04 +/- 0.21 vs 0.17 +/- 0.16,
      t = -3.99), while decreased negative functional connectivity with PCC was
      observed in left insula (-0.10 +/- 0.26 vs -0.30 +/- 0.19, t = 3.71), right
      inferior parietal lobule (0.02 +/- 0.18 vs -0.23 +/- 0.17, t = 5.20), left
      postcentral gyrus (0.08 +/- 0.26 vs -0.17 +/- 0.25, t = 4.06), left superior
      temporal gyrus (-0.04 +/- 0.25 vs -0.27 +/- 0.17, t = 4.27), right superior
      temporal gyrus (-0.08 +/- 0.25 vs -0.31 +/- 0.21, t = 3.80) and left fusiform
      gyrus (-0.01 +/- 0.25 vs -0.18 +/- 0.17, t = 3.57)(all P < 0.05, corrected).
      CONCLUSIONS: The connectivity of DMN between brain regions is abnormal in ADHD
      group. And the strengthen of negative relationship between DMN and task activated
      network becomes reduced. It is surmised that the decreased internal
      synchronization of default network and disrupted balance between DMN and
      prefrontal-parietal attentional networks may be important neural mechanisms of
      ADHD.

PMID- 24124740
TI  - [Dynamic changes of lung function in infant of different gestational ages].
AB  - OBJECTIVE: To explore the dynamic changes of lung function in infants born at
      different gestational ages without respiratory complications. METHODS: A total of
      110 cases of hospitalized neonatal patients were retrospectively recruited and
      analyzed at Shenzhen Children's Hospital from July 2010 to August 2012. By
      gestational age they were divided into 3 groups of full term (37-40 weeks, n =
      55, 29 males and 26 females) with an average birth weight (3.1 +/- 0.3) kg, late
      preterm group (34- < 37 weeks, n = 30, 18 males and 12 females) with an average
      birth weight (2.1 +/- 0.3) kg and early preterm (<34 weeks, n = 25, 16 males and
      9 females )with an average birth weight (1.4 +/- 0.3) kg. At Days 1, 14 and 28,
      lung function parameters of functional residual capacity (FRC) and lung clear
      index (LCI) were measured by multiple breath washouts with an ultrasonic flow
      meter and tidal breathing. One-way ANOVA was used for each index. RESULTS: Tidal
      expiratory flow 75% remaining tidal volume (TEF75), tidal expiratory flow 50%
      remaining tidal volume (TEF50) and tidal expiratory flow 25% remaining tidal
      volume (TEF25) gradually increased at Days 1, 14 and 28 in 3 groups. However
      respiratory rate (RR) gradually decreased. Compared with full term and late
      preterm, the early preterm infants had lower TEF75, TEF50 and TEF25, lower the
      ratios of time to peak expiratory flow and expiratory time (TPTEF/TE), lower
      ratios of volume to peak expiratory flow and expiratory volume (VPEF/VE) ((71 +/-
      21) and (66 +/- 16) vs (55 +/- 19)ml/s, (70 +/- 20) and (62 +/- 17) vs (51 +/-
      16)ml/s, (54 +/- 17) and (51 +/- 13) vs (38 +/- 10)ml/s, 37% +/- 8% and 34% +/-
      9% vs 29% +/- 6%, 38% +/- 6% and 33% +/- 8% vs 28% +/- 7%, F = 5.82, 8.74, 11.30,
      7.72, 16.40, all P < 0.01), higher RR and LCI at Day 28((49 +/- 6) and (51 +/- 8)
      vs (56 +/- 7)/min, 8.6 +/- 2.7 and 8.9 +/- 2.2 vs 10.8 +/- 2.0,F = 10.09, 7.15,
      both P < 0.05). At a matched post-menstrual age of 40 weeks, compared with full
      term and late preterm, the early preterm group had lower TEF50, TEF25, TPTEF/TE,
      VPEF/VE ((65 +/- 21) and (62 +/- 12) vs (50 +/- 17)ml/s,(51 +/- 13) and (47 +/-
      10) vs (39 +/- 10)ml/s, 36% +/- 8% and 31% +/- 7% vs 30% +/- 6%, 37% +/- 10% and
      32% +/- 8% vs 29% +/- 6%,F = 4.41, 8.23, 9.08, 7.35, all P < 0.05). CONCLUSIONS:
      Lung function improves with the elongation of days. The parameters of lung
      function in early infants are worse than those in full and late-preterm
      counterparts. At a corrected gestational age of 40 weeks, early preterm infants
      fail to achieve catch-up growth in lung function. Dynamic monitoring of lung
      function in preterm infants of different gestational ages is of vital importance
      for gauging respiratory maturity and assessing lung development especially for
      preterm infants.

PMID- 24124741
TI  - [Relevance between carotid plaque scores and the severity of coronary
      atherosclerosis].
AB  - OBJECTIVE: To explore the relevance between carotid plaque and the severity of
      coronary artery disease. METHODS: A total of 207 patients(149 males,58 females)
      undergoing coronary angiography were definitely diagnosed with coronary heart
      disease. They were divided into 3 groups of one-vessel disease (1VD, n = 69), two
      vessel disease (2VD, n = 57) and three-or-more vessel disease (3VD, n = 81) by
      the number of involved vessels. Their physical findings, biochemical data and
      carotid ultrasonographic results were collected. And the scores of Crouse,
      Gensini and Leaman were calculated to compare the relevance. RESULTS: No
      significant differences existed among all three groups except for a higher age
      and the presence of plaque in 2VD and 3VD groups than 1VD group ((63 +/- 11) and
      (60 +/- 11) vs (57 +/- 10)years old, 82%(n = 47) and 81%(n = 66) vs 65%(n = 45),
      both P < 0.05) . Crouse had a positive correlation with Gensini (r = 0.455, P <
      0.01) and Leaman scores (r = 0.358, P < 0.01) . CONCLUSION: Assessment of plaque
      scores by carotid ultrasonography is clinically relevant for predicting the
      severity of coronary artery disease.

PMID- 24124742
TI  - [Value of percentage of highly fluorescent lymphocytic cells for rapidly
      assessing septicemia in tumor patients].
AB  - OBJECTIVE: To evaluate the value of percentage of highly fluorescent lymphocytic
      cells (HFLC%) for rapidly assessing septicemia in tumor patients. METHODS: Blood
      samples were collected from 130 patients with tumors (60 septicemia patients and
      70 non-septicemia patients) and 80 healthy controls. HFLC% was analyzed with
      Sysmex XE-5000, the level of C-reactive protein (CRP) measured with a
      commercially available turbidimetric immunoassay kit and the level of
      procalcitonin (PCT) determined with a semiquantitative chromatographic
      immunoassay kit. The diagnostic values of HFLC% and CRP in septicemia were
      evaluated with ROC analysis. RESULTS: The values of HFLC% and CRP were
      significantly higher in the septicemia group than those in the non-septicemia and
      healthy groups (0.30% (0.10%-0.70%) vs 0.10% (0-0.20%), 0.10% (0-0.20%) ; 80.3
      (28.5-129.5) vs 3.3 (1.4-41.4) , 1.4 (0.6-2.5) mg/L, all P < 0.01) . The ROC-AUCs
      for HFLC% and CRP for a diagnosis of septicemia were 0.72 (sensitivity 71.7%,
      specificity 58.7%) and 0.92 (sensitivity 96.7%, specificity 82.0%). Both of them
      could judge septicemia better. Additionally, HFLC% was correlated with the levels
      of PCT and CRP (r = 0.637, 0.241, both P < 0.01). CONCLUSIONS: HFLC% may be used
      as a rapid and simple auxiliary indicator in the diagnosis of septicemia in
      patients with tumors. And it is conducive to make an early diagnosis of
      septicemia and avoid unnecessary use of antibiotics.

PMID- 24124743
TI  - [Therapeutic strategy of Bosniak category II renal cyst: a report of 52 cases].
AB  - OBJECTIVE: To evaluate the therapeutic strategy of Bosniak category II renal
      cyst. METHODS: A total of 52 cases of Bosniak category II renal cyst underwent
      surgery from 2004 to 2011. There were 32 males and 20 females with a mean age of
      48 years. Their average diameter of renal cysts was 4.7 cm. There were 25 left,
      23 right and 4 bilateral lesions. RESULTS: Renal cystectomy (n = 47) and radical
      nephrectomy (n = 5) were performed. Four cases of renal cyst with cystectomy had
      malignancy confirmed with intraoperative frozen section and underwent radical
      nephrectomy immediately. One case underwent radical nephrectomy in second stage
      because of a confirmation of malignant renal cyst after cystectomy. Malignant
      renal cyst were found in 5 cases and benign lesions in 47. The malignancy rate
      was 9.6% (5/52) with 14.3% (4/28) in IIF group and 4.2% (1/24) in non-IIF group.
      Forty-three cases were followed up for 1-8 years with 4 cases of malignancy and
      39 cases of benign lesions. One case of malignancy had pulmonary metastasis at 3
      years post-operation. CONCLUSIONS: Operation should be performed in IIF renal
      cyst and II cyst with a diameter of >5 cm. Follow-ups should be performed in
      other category II renal cysts, especially in young patients.

PMID- 24124744
TI  - [Feasibility of 13th lymph nodes as sentinels for periampullary carcinoma].
AB  - OBJECTIVE: To study the feasibility and clinical value of 13th lymph nodes in
      predicting general lymph nodes metastases for periampullary carcinoma. METHODS: A
      total of 77 patients with pathologically confirmed periampullary carcinoma were
      recruited. And 26 (18 males and 8 females, age 38-79 years) of them underwent
      Whipple procedures during which 1% methylene blue or nanogate carbon was injected
      into tumor bed. The other 51 patients as controls (33 males, 18 females, age 38
      78 years) . The dyed 13th lymph nodes were biopsied. Then routine lymphadenectomy
      was performed and their pathological results were analyzed. RESULTS: In the
      experimental group, the lymph node drainage area of cancer was identified.
      However, in contrast with 51 patients in the control group, the labeling of 13th
      lymph nodes did not significantly increase the number of cleaned lymph nodes
      (15.8 (3-54) vs 17.6 (6-40) , P = 0.460). CONCLUSION: 13th lymph nodes are non
      suitable as sentinels for predicting general lymph nodes metastases of
      periampullary carcinoma.

PMID- 24124745
TI  - [Efficacies of sorafenib plus interferon in advanced renal cell carcinoma: a
      report of 57 cases].
AB  - OBJECTIVE: To explore the efficacies and adverse events of sorafenib in the
      treatment of advanced metastatic renal cell carcinoma. METHODS: A total of 57
      patients with advanced kidney cancer were recruited from our hospital from April
      2007 to October 2011. They were divided into sorafenib group (A, n = 24) and
      sorafenib + IFN group (B, n = 33). The primary endpoints included objective
      response rate and progression-free survival (PFS). And the secondary endpoints
      were overall survival (OS) and incidence of adverse events. RESULTS: The mean
      medication time of group A was 15 (7-56) months. The outcomes were partial
      response (PR, n = 1), stable disease (SD, n = 8), progressive disease (PD, n = 1)
      and death (n = 14). The rates of objective response and disease control were 4.2%
      (1/24) and 37.5% (9/24) respectively. For group B, the mean medication time was
      15 (4-30) months. The outcomes were PR (n = 2), and include 2 patients of PR, 21
      examples of SD, 1 patient of PD and death. The rates of objective response and
      disease control were 6.1% (2/33) and 69.7% (23/33) respectively. Two groups had
      no significant difference in incidence or severity of adverse events (both P >
      0.05). CONCLUSIONS: As a safe and effective agent for advanced kidney cancer,
      sorafenib is well-tolerated in patients. The combined use of interferon may
      improve the therapeutic efficacies without an occurrence of adverse events.

PMID- 24124746
TI  - [Effect of Notch1 signal on hepatitis B virus X-mediated abnormal immune activity
      in renal tubular epithelial cells].
AB  - OBJECTIVE: To explore the expression of Notch1 receptor in renal tubular
      epithelial cells transfected with hepatitis B virus X(HBx) gene and its role in
      immunologic activity. METHODS: The eukaryotic vector pcDNA3.1/myc-HBx containing
      HBx gene or vector pcDNA3.1/myc-Notch1 containing Notch1 gene was transiently
      transfected into HK-2 cells. And the shRNA technique was used to silence Notch1.
      HK-2 cells were divided into 7 groups, including normal culture, pcDNA3.1/myc,
      HBx, HBx +pcDNA3.1/myc, HBx+Notch1, HBx+ shRNA and HBx+ Notch1 shRNA. Real-time
      PCR and Western blotting were used to detect the expression of Notch1. The
      expressions of MHC-IIand CD40 were examined by flow cytometry. And the
      supernatant contents of IL-4 and IFN-gamma were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The results of real-time PCR and Western
      blotting verified that HBx and Notch1 were successfully expressed in HK-2 cells
      after transfection. The transfection efficiency of shRNA was 70%. Compared with
      normal culture and pcDNA3.1/myc groups, the expression of Notch1 increased. The
      expressions of MHC-II and CD40 also significantly increased in the HBx+Notch1
      group (9.69% +/- 0.52% vs 4.90% +/- 0.32%, 21.56% +/- 0.71% vs 15.74% +/- 0.20%,
      both P < 0.05) . The supernatant level of IFN-gamma was lower in HBx+Notch1 group
      (11.9 +/- 1.7 vs 18.8 +/- 0.8, P < 0.05) while the level of IL-4 was higher than
      control groups (50.2 +/- 0.6 vs 28.1 +/- 1.2, P < 0.05). And the HBx+Notch1 shRNA
      group had the opposite results. CONCLUSIONS: An over-expression of HBx gene may
      up-regulate the expression of Notch1. And Notch1 promotes the expression of
      immune molecules of renal tubular epithelial cell and regulates the secretion of
      cytokines so as to cause injury of cells and dysfunction of immune
      microenvironment.

PMID- 24124747
TI  - [Effects of leflunomide on podocytes exposed to high glucose condition and its
      mechanism].
AB  - OBJECTIVE: To explore the protective effects of leflunomide (A771726) on the
      expression of podocalyxin, NF-kappaB and matrix metalloproteinase-9 (MMP-9) in
      podocytes exposed to high glucose environment and elucidate its mechanism.
      METHODS: Podocytes were cultured in high glucose. And the altered expressions of
      podocyte protein podocalyxin were detected by Western blotting at different
      timepoints. Then podocytes were divided into 4 groups of normal glucose control,
      leflunomide, high glucose and hypertonic control. The expression level of
      podocalyxin protein in each group was detected by Western blotting. And NF-kappaB
      p65 and phosphorylation of NF-kappaB p65 (P-NF-kappaBp65) in podocytes cultured
      in high glucose were detected at different timepoints. And then the podocytes
      were divided into 5 groups of normal glucose, mannitol, hypertonic control, high
      glucose, leflunomide and PDTC (NF-kappaB blocker). And the expressions of MMP-9
      protein in these groups were also detected by Western blotting. RESULTS: In the
      high glucose environment, the expression of podocalyxin declined instantly.
      Compared with the high-glucose group, the podocalyxin expression of the
      leflunomide group was significantly higher than the high glucose group (0.46 +/-
      0.04 vs 0.13 +/- 0.03, P < 0.05). After 30-minute stimulation by high glucose,
      the activation of NF-kappaB started and the expression of P-NF-kappaBp65 protein
      increased. Such activities peaked at 60 minutes and reverted to a basic level
      after 6 hours. Compared with the high glucose group, the expressions of MMP-9 in
      PDTC and leflunomide groups were significantly lower than the high glucose group.
      And the differences were statistically significant (0.71 +/- 0.01, 0.64 +/- 0.03
      vs 1.64 +/- 0.03, both P < 0.05). CONCLUSIONS: Leflunomide has protective effects
      on podocytes in high glucose. And its mechanism is possibly due to a lowered
      expression of MMP-9 through an inhibition of NF-kappaB activation.

PMID- 24124748
TI  - [Effects of mammalian-target-of-rapamycin pathway on lapatinib resistance in
      breast cancer MDA-MB-231 cells].
AB  - OBJECTIVE: To establish a lapatinib resistance cell line for elucidating the
      mechanisms of drug resistance of lapatinib in human breast cancer cells. METHODS:
      The human breast cancer MDA-MB-231 cells were exposed in an incremental dose of
      lapatinib to establish a lapatinib resistance rMDA-MB-231 cell line. The assay of
      methyl thiazolyl tetrazolium (MTT) was used to detect the cytotoxic activity of
      lapatinib against MDA-MB-231 and rMDA-MB-231 cells. The protein expression was
      detected by Western blot. Small interfering RNA was used to specifically knock
      down mammalian-target-of-rapamycin (mTOR) in rMDA-MB-231 cells. Apoptosis was
      determined by fluorescein isothiocyanate (FITC)-annexin V/PI staining and flow
      cytometry. RESULTS: The human breast cancer lapatinib resistance cell line rMDA
      MB-231 was induced by lapatinib. The half maximal inhibitory concentration (IC50)
      values of lapatinib against MDA-MB-231 and rMDA-MB-231 cells were (6.1 +/- 0.6)
      and (34.9 +/- 2.7) umol/L respectively (P < 0.01). Compared with MDA-MB-231
      cells, the protein expression of mTOR in rMDA-MB-231 cells was significantly up
      regulated. The protein expression of mTOR was significantly down-regulated by
      specific siRNA duplexes in rMDA-MB-231 cells. After siRNA interference, 20 umol/L
      lapatinib was added into control, negative siRNA control and mTOR-targeted siRNA
      groups respectively. The percents of cell apoptosis in control, negative control
      and targeted siRNA groups were 13.4% +/- 2.5%, 14.2% +/- 2.8% and 34.6% +/- 5.8%
      respectively, there was no significance between the first two groups (P > 0.05) ,
      and there was significant difference between the control and targeted siRNA group
      (P < 0.01) . CONCLUSIONS: The up-regulation of mTOR plays an important role in
      the lapatinib-resistant phenotype of human breast cancer rMDA-MB-231 cells. And
      the down-regulation of mTOR increases the apoptotic death of lapatinib against
      rMDA-MB-231 cells.

PMID- 24124749
TI  - [Establishment of acute myocardial infarction model in diabetic miniature pigs
      through video-assisted thoracoscopic surgery].
AB  - OBJECTIVE: To explore a new method of establishing acute myocardial infarction
      model in diabetic miniature pigs through video-assisted thoracoscopic surgery
      (VATS). METHODS: Seven normal miniature pigs and 7 diabetic miniature pigs
      underwent VATS by selectively ligating left anterior descending coronary artery
      and then were evaluated through serology, imaging and histology. RESULTS: The
      serum levels of troponin (cTni) and myoglobin (MYO) in both groups significantly
      increased by over 10 folds of upper normal limit after VATS. Echocardiography,
      MRI and histopathologic analysis showed that the affected myocardial parts were
      apex, left ventricular wall and interventricular septum cosco section. But heart
      function of diabetic miniature pigs were relatively lower; infarction area/area
      at-risk ratio higher (18.4% +/- 5.5% vs 5.3% +/- 3.9%, P = 0.03) , myocardial
      infarction through-wall degree more severe. These were in accordance with poor
      ischemic tolerance in diabetic myocardia. CONCLUSION: VATS is a safe and
      effective method for establishing AMI model in diabetic miniature pigs.

PMID- 24124750
TI  - [Laparoscopic with extralevator abdominoperineal excision for low rectal
      carcinoma].
AB  - OBJECTIVE: To explore the feasibility of laparoscopic with extralevator
      abdominoperineal excision (LELAPE group) for low rectal cancer. METHODS: From
      June 2011 to January 2013, 35 patients with low rectal cancer undergoing
      laparoscopic abdominoperineal excision at the Department of Gastroenterological
      Surgery, Beijing Hospital were analyzed retrospectively. Among them, 20 received
      laparoscopic abdominoperineal excision (LAPE group). There were 12 males and 8
      females with an average age of (63 +/- 6) years old. Another 15 patients
      underwent laparoscopic extralevator abdominoperineal excision (LELAPE group).
      There were 10 males and 5 females with an average age of (61 +/- 7) years old.
      Operative duration, blood loss volume, time of postoperative out-of-bed activity,
      recovery of gastrointestinal function, removal time of drainage tube, edge of
      perineal position take out stitches time, postoperative hospital stay and
      complication rates were relative analyzed. RESULTS: There was no significant
      difference in operative time, time of postoperative out-of-bed activity, recovery
      of gastrointestinal function, removal time of perineal stitches, postoperative
      hospital stay and complication rates between 2 groups ((259 +/- 52) vs (246 +/-
      55) min, (35 +/- 13) vs (33 +/- 9) d,(61 +/- 25) vs (63 +/- 20) h, (15.7 +/- 2.5
      ) vs (16.8 +/- 2.9) d, (12 +/- 3) vs (15 +/- 4) d, 2/15 vs 3/20, all P > 0.05).
      Blood loss volume of perineal position in LELAPE group was less than those in
      LAPE group ((76 +/- 31) vs (148 +/- 36) ml, P < 0.05). Removal of perineal
      drainage tube in LELAPE group was earlier than that in LAPE group ((6.2 +/- 1.6)
      vs (10.3 +/- 1.8) d, P < 0.05). CONCLUSION: LELAPE is a safe and feasible
      surgical approach for low rectal cancer.

PMID- 24124751
TI  - Significance of the anti-aging protein Klotho.
AB  - The Klotho gene was identified as an 'aging suppressor' in mice. Overexpression
      of the Klotho gene extends lifespan and defective Klotho results in rapid aging
      and early death. Both the membrane and secreted forms of Klotho have biological
      activity that include regulatory effects on general metabolism and a more
      specific effect on mineral metabolism that correlates with its effect on aging.
      Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also
      functions as a humoral factor that regulates cell survival and proliferation,
      vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a
      potential tumor suppressor. Moreover, Klotho protects against several pathogenic
      processes in a FGF23-independent manner. These processes include cancer
      metastasis, vascular calcification, and renal fibrosis. This review covers the
      recent advances in Klotho research and discusses novel Klotho-dependent
      mechanisms that are clinically relevant in aging and age-related diseases.

PMID- 24124752
TI  - Protein dielectric constants determined from NMR chemical shift perturbations.
AB  - Understanding the connection between protein structure and function requires a
      quantitative understanding of electrostatic effects. Structure-based
      electrostatic calculations are essential for this purpose, but their use has been
      limited by a long-standing discussion on which value to use for the dielectric
      constants (epsilon(eff) and epsilon(p)) required in Coulombic and Poisson
      Boltzmann models. The currently used values for epsilon(eff) and epsilon(p) are
      essentially empirical parameters calibrated against thermodynamic properties that
      are indirect measurements of protein electric fields. We determine optimal values
      for epsilon(eff) and epsilon(p) by measuring protein electric fields in solution
      using direct detection of NMR chemical shift perturbations (CSPs). We measured
      CSPs in 14 proteins to get a broad and general characterization of electric
      fields. Coulomb's law reproduces the measured CSPs optimally with a protein
      dielectric constant (epsilon(eff)) from 3 to 13, with an optimal value across all
      proteins of 6.5. However, when the water-protein interface is treated with finite
      difference Poisson-Boltzmann calculations, the optimal protein dielectric
      constant (epsilon(p)) ranged from 2 to 5 with an optimum of 3. It is striking how
      similar this value is to the dielectric constant of 2-4 measured for protein
      powders and how different it is from the epsilon(p) of 6-20 used in models based
      on the Poisson-Boltzmann equation when calculating thermodynamic parameters.
      Because the value of epsilon(p) = 3 is obtained by analysis of NMR chemical shift
      perturbations instead of thermodynamic parameters such as pK(a) values, it is
      likely to describe only the electric field and thus represent a more general,
      intrinsic, and transferable epsilon(p) common to most folded proteins.

PMID- 24124753
TI  - What do letters to the editor publish about randomized controlled trials? A cross
      sectional study.
AB  - BACKGROUND: To identify published letters to the editor (LTE) written in response
      to randomized controlled trials (RCTs), determine the topics addressed in the
      letters, and to examine if these topics were affected by the characteristics and
      results of the RCTs. METHODS: Comparative cross-sectional study of a
      representative sample of RCTs from a set of high-impact medical journals (BMJ,
      Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published
      LTE were searched from these 5 journals in 2007. Data were collected on RCTs and
      their characteristics (author affiliation, funding source, intervention, and
      effect on the primary outcome) and the topics addressed in published LTE related
      to these RCTs. Analysis included chi-square and regression analysis (RCT
      characteristics) and thematic analysis (LTE topics). RESULTS: Of 334 identified
      RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were
      identified. Most RCTs, tested drug interventions (68%), were funded by government
      (54%) or industry (33%), and described an intervention that had a positive impact
      on the primary outcome (62%). RCT authors were primarily affiliated with an
      academic centre (78%). Ninety percent of the 623 LTE topics concerned
      methodological issues regarding the analysis, intervention, and population in the
      RCT. There was a significant association between funding source and impact on
      outcomes (p = 0.002) or type of intervention tested (p = 0.001) in these trials.
      Clinical and "Other" LTE topics were more likely to be published in response to a
      government funded RCT (p = 0.005 and p = 0.033, respectively); no other
      comparisons were significant. CONCLUSIONS: This study showed that most LTE are
      about methodological topics, but found little evidence to support that these
      topics are affected by the characteristics or results of the RCTs. The lack of
      association may be explained by editorial censorship as a small proportion of LTE
      that are submitted are actually published.

PMID- 24124754
TI  - Epsilon-near-zero strong coupling in metamaterial-semiconductor hybrid
      structures.
AB  - We present a new type of electrically tunable strong coupling between planar
      metamaterials and epsilon-near-zero modes that exist in a doped semiconductor
      nanolayer. The use of doped semiconductors makes this strong coupling tunable
      over a wide range of wavelengths through the use of different doping densities.
      We also modulate this coupling by depleting the doped semiconductor layer
      electrically. Our hybrid approach incorporates strong optical interactions into a
      highly tunable, integrated device platform. 

PMID- 24124755
TI  - Do theoretical potential and advanced technology justify the use of high-dose
      rate brachytherapy as monotherapy for prostate cancer?
AB  - Low-dose rate brachytherapy (LDR-BT), involving implantation of radioactive seeds
      into the prostate, is an established monotherapy for most low-risk and select
      intermediate- and high-risk prostate cancer patients. High-dose rate
      brachytherapy (HDR-BT) is an advanced technology theorized to be more
      advantageous than LDR-BT from a radiobiological and radiophysics perspective, to
      the patient himself, and in terms of resource allocation. Studies of HDR-BT
      monotherapy have encouraging results in terms of biochemical control, patient
      survival, treatment toxicity and erectile preservation. However, there are still
      certain limitations that preclude recommending HDR-BT monotherapy for prostate
      cancer outside the setting of a clinical trial. HDR-BT monotherapy should be
      considered experimental at present. 

PMID- 24124756
TI  - Effects of high angular momentum on the unimolecular dissociation of CD2CD2OH:
      theory and comparisons with experiment.
AB  - This paper explores the dynamics of a highly rotationally and vibrationally
      excited radical, CD2CD2OH. The radical is produced from the 193 nm
      photodissociation of 2-bromoethanol-d4, so it is imparted with high angular
      momentum and high vibrational energy and subsequently dissociates to several
      product channels. This paper focuses on characterizing its angular momentum and
      modeling its effect on the product channels, including the HOD + vinyl-d3 product
      channel resulting from a frustrated dissociation of the radical originally en
      route to OH + ethene-d4 that instead results in D atom abstraction. Our impulsive
      model of the initial photodissociation shows that, for some cases, upward of 200
      au of angular momentum is imparted, which greatly affects the dynamics of the
      competing product channels. Using a permutationally invariant potential energy
      surface and quasiclassical trajectories, we simulated the dissociation dynamics
      of CD2CD2OH and compared these results to those of Kamarchik et al. (J. Phys.
      Chem. Lett. 2010, 1, 3058-3065), who studied the dynamics of CH2CH2OH with zero
      angular momentum. We found that the recoil translational energy distribution for
      radicals that dissociated to OH + C2D4 matched experiment closely only when high
      angular momentum of the initial radical was explicitly included in the trajectory
      calculations. Similarly, the rate constant for dissociation changes when
      rotational energy was added to the vibrational energy in the initial conditions.
      Lastly, we applied the sketch-map dimensionality reduction technique to analyze
      mechanistic information leading to the vinyl + water product channel. Projecting
      the ab initio intrinsic reaction coordinates onto the lower dimensional space
      identified with sketch map offers new insight into the dynamics when one looks at
      the simulated trajectories in the lower dimensional space. Further analysis shows
      that the transition path resembles a frustrated dissociation of the OH + ethene
      radical adduct, followed instead by branching to vinyl + water when the leaving
      OH group encounters a nearby D atom on the ethene moiety. This characterization
      is in accord with the one made previously. We show that the transition path
      bifurcation between the two similar channels occurs at carbon-oxygen distances
      and oxygen-abstracted deuterium distances of 2-2.5 A controlled by the C-O-D bond
      angle with large angles preferentially branching to the water plus vinyl product
      state. The experimental branching ratios were not reproduced by theory, however,
      due partly to the insufficient quality of the fitted potential surface. We also
      have evidence of a minor product channel, HD + vinoxy-d3, from our molecular
      dynamics simulations that allows us to assign the HD signal in prior experimental
      work. 

PMID- 24124757
TI  - The C-terminal cysteine of turbot Scophthalmus maximus translationally controlled
      tumour protein plays a key role in antioxidation and growth-promoting functions.
AB  - The translationally controlled tumour protein (TCTP) of turbot Scophthalmus
      maximus (SmTCTP) contains only one cysteine (Cys170) at the C-terminal end. The
      biological role of this C-terminal Cys170 in the antioxidation and growth
      promoting functions of SmTCTP was examined by site-directed mutation of C170A
      (Cys170 ->Ala170). It was found that C170A mutation not only obviously decreased
      the antioxidation capacity of the mutant-smtctp-transformed bacteria exposed to
      0.22 mM hydrogen peroxide, but also significantly interrupted the normal growth
      and survival of the mutant-smtctp-transformed bacteria and flounder Paralichthys
      olivaceus gill (FG) cells, indicating a key role played by Cys170 in the
      antioxidation and growth-promoting functions of SmTCTP. This study also suggested
      that the self-dimerization or dimerization with other interacting proteins is
      critical to the growth-promoting function of SmTCTP.

PMID- 24124759
TI  - Effect of establishing pain committee on the pain assessment skills of paediatric
      nurses.
AB  - Successful pain management relies on pain assessment. The purpose of this study
      is to investigate the effect of establishing pain committee on pain assessment
      skills of paediatric nurses. We used a quasi-experimental design. The study was
      conducted in surgery, emergency and orthopaedic wards of two teaching hospitals
      selected through simple random sampling. The intervention consisted of
      establishing a pain committee, the steps of which included organizing (3 months),
      holding workshop (five sessions) and clinical training (1 week). We found that
      the scores in the intervention group were significantly higher than those in the
      control group. Therefore, establishing pain committee in the management level of
      nursing improves nurses' pain assessment skills. 

PMID- 24124758
TI  - Achieving interconnected pore architecture in injectable PolyHIPEs for bone
      tissue engineering.
AB  - Template polymerization of a high internal phase emulsion (polyHIPE) is a
      relatively new method to produce tunable high-porosity scaffolds for tissue
      regeneration. This study focuses on the development of biodegradable injectable
      polyHIPEs with interconnected porosity that have the potential to fill bone
      defects and enhance healing. Our laboratory previously fabricated biodegradable
      polyHIPEs that cure in situ upon injection; however, these scaffolds possessed a
      closed-pore morphology, which could limit bone ingrowth. To address this issue,
      HIPEs were fabricated with a radical initiator dissolved in the organic phase
      rather than the aqueous phase of the emulsion. Organic-phase initiation resulted
      in macromer densification forces that facilitated pore opening during cure.
      Compressive modulus and strength of the polyHIPEs were found to increase over 2
      weeks to 43+/-12 MPa and 3+/-0.2 MPa, respectively, properties comparable to
      cancellous bone. The viscosity of the HIPE before cure (11.0+/-2.3 Pa.s) allowed
      for injection and filling of the bone defect, retention at the defect site during
      cure under water, and microscale integration of the graft with the bone.
      Precuring the materials before injection allowed for tuning of the work and set
      times. Furthermore, storage of the HIPEs before cure for 1 week at 4 degrees C
      had a negligible effect on pore architecture after injection and cure. These
      findings indicate the potential of these emulsions to be stored at reduced
      temperatures and thawed in the surgical suite before injection. Overall, this
      work highlights the potential of interconnected propylene fumarate dimethacrylate
      polyHIPEs as injectable scaffolds for bone tissue engineering. 

PMID- 24124760
TI  - Stimulating the neurotrophic and angiogenic properties of human adipose-derived
      stem cells enhances nerve repair.
AB  - In future, adipose-derived stem cells (ASC) might be used to treat neurological
      disorders. In this study, the neurotrophic and angiogenic properties of human ASC
      were evaluated, and their effects in a peripheral nerve injury model were
      determined. In vitro growth factor stimulation of the cells resulted in increased
      secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived
      neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and
      angiopoietin-1 proteins. Conditioned medium from stimulated cells increased
      neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated
      cells showed an enhanced ability to induce capillary-like tube formation in an in
      vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to
      bridge a 10 mm rat nerve gap. After 2 weeks, the animals treated with control or
      stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells
      evoked more total axon growth. Analysis of regeneration and apoptosis-related
      gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and
      activating transcription factor 3 (ATF-3) expression in the spinal cord and
      reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced
      by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of
      the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and
      angiogenic factors, creating a more desirable microenvironment for nerve
      regeneration.

PMID- 24124761
TI  - Effects of intra- and post-operative ischemia on the metabolic profile of
      clinical liver tissue specimens monitored by NMR.
AB  - Metabolomic profiles of tissues could greatly contribute to advancements in
      personalized medicine but are influenced by differences in adopted preanalytical
      procedures; nonhomogeneous pre- and post-excision ischemia times are potential
      sources of variability. In this study, we monitored the impact of ischemia on the
      metabolic profiles, acquired with high-resolution magic-angle-spinning (1)H NMR,
      of 162 human liver samples collected during and up to 6 h after routine surgery.
      The profiles changed significantly as a function of intraoperative warm ischemia
      (WI) and postresection cold ischemia (CI) time, with significant variations in
      the concentration of the same 16 metabolites. Therefore, a tight control of the
      preanalytical phase is essential for reliable metabolomic analyses of liver
      diseases. The NMR profiles provide a reliable "fingerprint" of ischemia and have
      predictive value: the best-performing predictive models are found to discriminate
      extreme time points of CI (0' vs 360 ') in the training set with cross-validation
      accuracy of ~90%; samples in the validation cohort can discriminate short (<=60')
      from long (>=180') CI with an accuracy of ~80%. For WI, the corresponding figures
      are 95.6 and 92%, respectively. Therefore, ischemia NMR profiles might become a
      tool for tissue quality control in biobanks.

PMID- 24124762
TI  - Seasonal variations in the fatty acid profile of milk from yaks grazing on the
      Qinghai-Tibetan plateau.
AB  - An experiment was conducted to study the seasonal changes in the fatty acid
      profile of milk from yaks (Bos grunniens) when kept at altitudes of 3000 m above
      sea level (a.s.l.) and higher. Data and samples were collected in summer (July),
      autumn (September), winter (November) and spring (March) from ten lactating yaks
      (four in spring). The yaks grazed pastures adjacent to the farm building
      throughout the year. In spring only they received 0.6 kg crop by-products per day
      (dry matter basis). Fresh alpine grasses, available in summer and autumn, showed
      high concentrations of alpha-linolenic acid (46-51 g/100 g lipids) compared with
      the dry, yellow vegetation of winter and spring (16 g/100 g lipids). In autumn
      and summer, the milk fat had higher concentrations of polyunsaturated fatty acids
      than in winter. These polyunsaturated fatty acids were comprised of vaccenic
      acid, rumenic acid and alpha-linolenic acid, which are all considered beneficial
      to human health. The rare fatty acid, gamma-linolenic acid, was also detected in
      yak milk, especially in the milk obtained in spring. The results suggest that yak
      milk, which is the most important basic food of the Tibetan herders, has the most
      favourable fatty acid profile when yaks grazed green pasture, which also
      corresponds to the period of highest milk production. 

PMID- 24124763
TI  - Protective effect of pumpkin seed extract on sperm characteristics, biochemical
      parameters and epididymal histology in adult male rats treated with
      cyclophosphamide.
AB  - Cancer treatment with cyclophosphamide (CP) may result in reproductive toxicity
      as one of its side effects. The pumpkin seed is a rich natural source of
      antioxidant. We have assessed the possible protective efficacy of pumpkin seed
      extract on sperm characteristics, biochemical parameters and epididymal histology
      of CP-treated rats. Male adult Wistar rats were categorised into four groups.
      Group 1 served as control and received intraperitoneal (IP) injection of isotonic
      saline solution. Group 2 rats were treated with CP by IP injection in a single
      dose of 100 mg/kg body weight, only once. Group 3 and 4 received CP plus 300 and
      600 mg/kg pumpkin seed extract respectively. Six weeks after treatment, sperm
      characteristics, biochemical parameters and histopathological changes were
      examined. Results showed that, sperm characteristics in CP-treated rats were
      significantly decreased. Biochemical analysis results showed that the co
      administration of 300 mg pumpkin seed extract could increase the total
      antioxidant capacity (TAC) level significantly. In CP-treated rats,
      histopathological changes such as vacuolisation, disorganisation and separation
      of epididymal epithelium were observed as well. Interestingly, pumpkin seed
      extract could improve the above-mentioned parameters remarkably in CP-treated
      rats. Our findings indicated that pumpkin seed extract might be used as
      protective agent against CP-induced reproductive toxicity.

PMID- 24124764
TI  - Mothers' lived experiences of support when living with young children with
      congenital heart defects.
AB  - PURPOSE: The purpose of this study was to illuminate the meanings of support as
      disclosed by mothers of children with congenital heart defects (CHD). DESIGN AND
      METHOD: Narrative interviews were conducted with 10 mothers of children with CHD.
      A phenomenological-hermeneutic method was used for interpretation of the
      transcribed interviews. RESULTS: The comprehensive understanding of mothers'
      lived experiences of support emerged as the experiences of receiving good
      support, receiving "poor support," and absence of support. PRACTICE IMPLICATIONS:
      Mothers receiving person-centered and family-centered care feel more supported
      and are more likely to adapt to the stresses of parenting a child with CHD.

PMID- 24124765
TI  - Interaction between a transition-metal fluoride and a transition-metal hydride:
      water-mediated hydrofluoric acid evolution following fluoride solvation.
AB  - The reaction between the nickel(II) PCP pincer fluoride complex ((tBu)PCP)Ni(F)
      [(tBu)PCP = 2,6-C6H3(CH2P(t)Bu2)2] and the tungsten(II) carbonyl hydride
      CpW(H)(CO)3 (Cp = eta(5)-C5H5(-)) leads to hydrofluoric acid evolution and
      formation of the bimetallic isocarbonylic species [CpW(CO)2(MU-kappa,C:kappa,O
      CO)...Ni((tBu)PCP)]. The process has been monitored through multinuclear ((19)F,
      (31)P{(1)H}, (1)H) variable-temperature NMR spectroscopy, collecting (19)F T1
      data values for a fluoride ligand bound to a transition metal. The extremely
      short relaxation time (minimum value of 13 ms at 193 K) is ascribed to the large
      chemical shift anisotropy of the Ni-F bond (688 ppm). The in-depth NMR analysis
      has revealed that the fluoride-hydride interaction is not direct but water
      mediated, at odds with what was previously observed for the "hydride-hydride"
      case ((tBu)PCP)Ni(H)/CpW(H)(CO)3. Kinetic measurements have unveiled that the
      first step of the overall mechanism is thought to be solvation of the fluoride
      ligand (as a result of Ni-F...H2O hydrogen bonding), while further reaction of
      the solvated fluoride with CpW(H)(CO)3 is extremely slow and competes with the
      side reaction of fluoride replacement by a water molecule on the nickel center to
      form the [((tBu)PCP)Ni(H2O)](+) aquo species. Finally, density functional theory
      analysis of the solvation process through a discrete + continuum model has been
      accomplished, at the M06//6-31+G(d,p) level of theory, to support the mechanistic
      hypothesis. 

PMID- 24124766
TI  - Visuospatial, visuoperceptual, and visuoconstructive abilities in congenital
      hypothyroidism.
AB  - Individuals with congenital hypothyroidism (CH), even those diagnosed and treated
      early, experience selective cognitive deficits, the most striking of which
      involves the visuocognitive domain. However, the range and nature of their
      visuocognitive disturbances is not fully understood. We assessed a range of
      higher-order visuocognitive abilities in 19 children and adolescents with CH and
      19 age- and sex-matched typically developing peers (TD) using a battery of
      neuropsychological tests and a novel self-report measure of sense of direction.
      CH scored lower than TD on direct tests of visuocognitive function (judging line
      orientation, parts-to-whole localization, copying three-dimensional block towers,
      discriminating designs, and matching unfamiliar faces in 3/4 profile-view) as
      well as on self-reported problems in spatial ability. Visuocognitive problems
      were not global as CH and TD did not differ at copying two-dimensional block
      designs, mentally rotating and matching abstract shapes, or at matching
      unfamiliar front-view faces, design features, or designs that engaged either
      figure-ground segregation, visual constancy, or closure. Early and concurrent
      thyroid stimulating hormone (TSH) levels were associated with visuocognitive
      ability, although attention and working memory were not. Individuals with CH
      exhibit selective visuocognitive weaknesses, some of which are related to early
      and concurrent TSH levels.

PMID- 24124768
TI  - Second nonmelanoma skin cancer in Spain: frequency and chronology.
AB  - BACKGROUND: Follow-up of patients with nonmelanoma skin cancer (NMSC) is mainly
      aimed at the early diagnosis of local recurrences and early detection of a
      subsequent or second NMSC (sNMSC). However, the frequency and chronology of sNMSC
      have not been widely studied in the literature. OBJECTIVES: To assess the
      frequency and chronology of developing an sNMSC. METHODS: This was a
      retrospective longitudinal study of patients with a first NMSC excised and
      diagnosed at the Hospital Universitario Virgen Macarena (Seville, Spain) between
      1 January 1998 and 31 December 2000 and followed up until 31 December 2009. Age,
      sex, histological type of NMSC (basal cell carcinoma, squamous cell carcinoma),
      anatomical location, and the diagnosis date of both the first NMSC and the sNMSC
      were recorded. Main outcomes assessed were the frequency of developing an sNMSC,
      the annual probability density and the median sNMSC-free survival through the
      Kaplan-Meier model. RESULTS: A total of 926 patients with a first single NMSC
      were enrolled and followed up for a median time of 81.9 months. Two hundred and
      nine patients (22.6%) developed an sNMSC in a median time of 28.3 months.
      Probability density of a sNMSC ranged from 0.003 to 0.004 for the first 5 years
      of follow-up. Age >= 40 years (P = 0.02), and first NMSC excised from the limbs
      (P = 0.03) were predictors of developing an sNMSC. CONCLUSIONS: The development
      of an sNMSC is a common event in patients previously diagnosed with an NMSC
      especially during the first 5 years of follow-up. This finding should be taken
      into consideration when designing follow-up guidelines for patients with NMSC.

PMID- 24124767
TI  - Proteomic profiling of serum samples from chikungunya-infected patients provides
      insights into host response.
AB  - BACKGROUND: Chikungunya is a highly debilitating febrile illness caused by
      Chikungunya virus, a single-stranded RNA virus, which is transmitted by Aedes
      aegypti or Aedes albopictus mosquito species. The pathogenesis and host responses
      in individuals infected with the chikungunya virus are not well understood at the
      molecular level. We carried out proteomic profiling of serum samples from
      chikungunya patients in order to identify molecules associated with the host
      response to infection by this virus. RESULTS: Proteomic profiling of serum
      obtained from the infected individuals resulted in identification of 569
      proteins. Of these, 63 proteins were found to be differentially expressed (>= 2
      fold) in patient as compared to control sera. These differentially expressed
      proteins were involved in various processes such as lipid metabolism, immune
      response, transport, signal transduction and apoptosis. CONCLUSIONS: This is the
      first report providing a global proteomic profile of serum samples from
      individuals infected with the chikungunya virus. Our data provide an insight into
      the proteins that are involved as host response factors during an infection.
      These proteins include clusterin, apolipoproteins and S100A family of proteins.

PMID- 24124771
TI  - Microsclerodermins from terrestrial myxobacteria: an intriguing biosynthesis
      likely connected to a sponge symbiont.
AB  - The microsclerodermins are unusual peptide natural products exhibiting potent
      antifungal activity reported from marine sponges of the genera Microscleroderma
      and Theonella . We here describe a variety of microbial producers of
      microsclerodermins and pedeins among myxobacteria along with the isolation of
      several new derivatives. A retrobiosynthetic approach led to the identification
      of microsclerodermin biosynthetic gene clusters in genomes of Sorangium and
      Jahnella species, allowing for the first time insights into the intriguing hybrid
      PKS/NRPS machinery required for microsclerodermin formation. This study reveals
      the biosynthesis of a "marine natural product" in a terrestrial myxobacterium
      where even the identical structure is available from both sources. Thus, the
      newly identified terrestrial producers provide access to additional chemical
      diversity; moreover, they are clearly more amenable to production optimization
      and genetic modification than the original source from the marine habitat. As
      sponge metagenome data strongly suggest the presence of associated myxobacteria,
      our findings underpin the recent notion that many previously described "sponge
      metabolites" might in fact originate from such microbial symbionts. 

PMID- 24124769
TI  - Ubiquinol-10 supplementation activates mitochondria functions to decelerate
      senescence in senescence-accelerated mice.
AB  - AIM: The present study was conducted to define the relationship between the anti
      aging effect of ubiquinol-10 supplementation and mitochondrial activation in
      senescence-accelerated mouse prone 1 (SAMP1) mice. RESULTS: Here, we report that
      dietary supplementation with ubiquinol-10 prevents age-related decreases in the
      expression of sirtuin gene family members, which results in the activation of
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha),
      a major factor that controls mitochondrial biogenesis and respiration, as well as
      superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are
      major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also
      increase mitochondrial complex I activity and decrease levels of oxidative stress
      markers, including protein carbonyls, apurinic/apyrimidinic sites,
      malondialdehydes, and increase the reduced glutathione/oxidized glutathione
      ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1alpha by increasing
      cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP
      response element-binding protein (CREB) and AMP-activated protein kinase (AMPK).
      INNOVATION AND CONCLUSION: These results show that ubiquinol-10 may enhance
      mitochondrial activity by increasing levels of SIRT1, PGC-1alpha, and SIRT3 that
      slow the rate of age-related hearing loss and protect against the progression of
      aging and symptoms of age-related diseases.

PMID- 24124770
TI  - Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in
      ovarian cancer.
AB  - BACKGROUND: Hyaluronan (HA) an important component of the extracellular matrix,
      has been linked to tumor progression and drug resistance in several malignancies.
      However, limited data is available for ovarian cancer. This study investigated
      the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and
      membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer
      chemoresistance. METHODS: We investigated the ability of HA to block the
      cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the
      expression of ABC transporters in ovarian cancer cells. We also examined HA serum
      levels in ovarian cancer patients prior to and following chemotherapy and
      assessed its prognostic relevance. RESULTS: HA increased the survival of
      carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR
      5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and
      ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels
      were significantly increased in patients following platinum based chemotherapy
      and at both 1st and 2nd recurrence when compared with HA levels prior to
      treatment. High serum HA levels (>50 MUg/ml) prior to chemotherapy treatment were
      associated with significantly reduced progression-free (P = 0.014) and overall
      survival (P = 0.036). HA production in ovarian cancer cells was increased in
      cancer tissues collected following chemotherapy treatment and at recurrence.
      Furthermore HA treatment significantly increased the expression of ABC drug
      transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells
      expressing CD44. The effects of HA and carboplatin on ABC transporter expression
      in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly,
      HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to
      carboplatin. CONCLUSIONS: Our findings indicate that carboplatin chemotherapy
      induces HA production which can contribute to chemoresistance by regulating ABC
      transporter expression. The HA-CD44 signaling pathway is therefore a promising
      target in platinum resistant ovarian cancer.

PMID- 24124772
TI  - Smoking habit profile and health-related quality of life.
AB  - BACKGROUND: Few studies have investigated the relationship between smoking and
      health-related quality of life (HRQOL), and the results are not consistent. The
      aim of this study is to explore the association between smoking and HRQOL.
      METHOD: Cross-sectional study of 714 Spanish adults (44.7% never smokers and
      55.3% smokers) without diagnosis of physical or mental disorder. Each participant
      provided information about different sociodemographic variables and data on
      HRQOL. Smokers also reported smoking-related information about smoking-related
      variables. RESULTS: Nicotine dependence was not associated with the physical
      dimension of HRQOL, but in the mental component, nicotine dependent smokers
      showed worse HRQOL than never smokers (p = 0.004) and than non-nicotine dependent
      smokers (p = 0.014). There were no differences between no-nicotine dependent
      smokers and never smokers. Smoking status (non smokers vs. smokers), number of
      cigarettes smoked per day, stage of change, quit attempts in the past year or age
      of smoking onset were not related to HRQOL. CONCLUSIONS: In subjects without
      physical or mental diseases, only nicotine dependent smokers showed a significant
      impairment in the mental component of HRQOL. Therefore, it is important to
      consider nicotine dependence in the relationship between smoking and HRQOL.

PMID- 24124773
TI  - Diagnostic agreement between the Personality Diagnostic Questionnaire-4+ (PDQ-4+)
      and its Clinical Significance Scale.
AB  - BACKGROUND: The Personality Diagnostic Questionnaire-4+ (PDQ-4+) is composed of a
      self-report and an interview, the Clinical Significance Scale, but no studies
      have reported joint findings. This study is the first to examine the diagnostic
      agreement between the Spanish version of the PDQ-4+ self-report and its
      corresponding interview. METHOD: The sample comprised 235 psychiatric outpatients
      who were assessed with both instruments. RESULTS: The interview reduced to one
      half the number of diagnoses provided by self-report (83.4% to 38.3%; mean number
      of diagnoses 3.29 to .62). Diagnostic agreement was between fair and moderate
      (mean kappa .45 for PDQ-4+ total score). CONCLUSIONS: Findings suggest the
      utility of jointly administering the PDQ-4+ and its Clinical Significance Scale
      to screen for the presence or absence of personality disorders (PDs).
      Modifications in the diagnostic cut-offs for individual PDs and the PDQ-4+ total
      score may improve the efficacy of the instrument.

PMID- 24124774
TI  - Relationship between drug use and psychopathological variables of risk in
      university students.
AB  - BACKGROUND: Research has been studying the relationships between drug use and the
      risk of suffering psychopathological disorders. This study analyzed the
      relationships existing between this use and certain psychotic disorder risk
      variables: hallucination, schizotypy and cognitive fusion. METHOD: Several
      screening questionnaires on drug use (CAGE), a questionnaire on "cognitive
      fusion" (TAFS), another on hallucination proneness (LSHS-R) and another on
      schizotypy (O-LIFE-R) were given to a sample of 308 students at the University of
      Almeria with a mean age of 19.51 years (SD= 2.11). RESULTS: The results found
      show how cognitive fusion is positively related to use of cannabis and cocaine,
      the scores on the schizotypy scale correlated positively with use of alcohol and
      cannabis, and the scores on a hallucination proneness correlated positively to
      use of cannabis. Regression equations were found that predicted the use of these
      substances from the variables of vulnerability to suffering from schizophrenia
      spectrum disorders. CONCLUSIONS: The results show an association between drug use
      and the risk variables studied.

PMID- 24124775
TI  - Theory of mind and language comprehension in schizophrenia.
AB  - BACKGROUND: Theory of mind (ToM) is the natural ability to attribute/infer mental
      states about ourselves and others. The study of the limits of this capacity in
      autism-spectrum disorders has been projected more recently to the case of
      schizophrenia. METHOD: We review the studies on ToM deficiency in schizophrenia,
      based on the link observed by Chris Frith between psychotic symptoms and
      mentalizing anomalies, with particular attention to the implications of ToM in
      linguistic communication in the field of figurative language comprehension.
      RESULTS: The data support a connection between ToM deficits and psychotic
      symptoms. In schizophrenia, the deficit in ToM appears to be specific and not
      dependent on more general cognitive abilities, and according to the evidence
      examined, it resembles a trait more than a state condition. The analysis of
      results shows that anomalies in ToM have projections on pragmatic aspects of
      language comprehension. CONCLUSIONS: ToM deficits showed by schizophrenic
      patients are especially linked to difficulties in understanding figurative
      language, beyond the influence of intelligence and executive functions.

PMID- 24124776
TI  - Identification of degrees of anxiety in children with three- and five-face facial
      scales.
AB  - BACKGROUND: Facial scales are used in the assessment of emotional states. The
      scales present different numbers of faces to measure the varying levels of
      intensity of children's emotional responses. This paper seeks to analyze the
      whether the subjects are able to match the appropriate descriptors of a degree of
      anxiety with the corresponding facial image. METHOD: A sample of 463 children
      aged 6 to 12 years was taken from the Autonomous Communities of Murcia and the
      Balearics. RESULTS: Significant differences were obtained among the six-year
      olds, M = 2.58 ( SD = 0. 85), in the three-face scale and M = 2.98 ( SD = 1.52)
      in the five-face scale. From 7 years on, there were no significant differences in
      the number of correct responses between the two scales. In general, girls scored
      higher than boys on both the three-face scale ( M = 2.89, SD = 0.50 vs. M = 2.75,
      SD = 0.70) and the five-face scale ( M = 4.08, SD = 1.41 vs. M = 3.76, SD =
      1.56). CONCLUSION: The three-face scale is more appropriate for the correct
      matching of descriptors to different degrees of anxiety for children aged 6 to 12
      years, whereas the five-face scale is more suited to children over 6 years.

PMID- 24124777
TI  - Neuropsychological syndromes in multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment in multiple sclerosis (MS) is common (45
      65%).Deficits occur in speed of information processing (SIP), memory, attention,
      executive functions (EF) and visuoconstruction.Involvement of cognitive functions
      like language and gnosis is rare and lesser known. Our aim is to describe the
      cognitive function and the clinical and radiological features of five patients
      with MS and with neuropsychological syndromes (NPS). METHOD: Retrospective review
      of MS patients with NPS studied, using specific tests of SIP, memory, attention,
      EF, visuo-spatial abilities, praxis and language. RESULTS: The sample included
      four women (3 relapsing-remitting MS/1 secondary progressive MS) and one man with
      primary progressive MS (aged between 30-55 years). Cognitive symptoms were the
      initial complaint in three cases. Three cases presented apperceptive agnosia and
      constructive apraxia, one case presented alexia with agraphia and the fifth
      patient presented motor aphasia. Four patients suffered cognitive dysfunction
      considered typical of MS. Magnetic resonance imaging (MR) in all cases showed
      high lesion volumes in T1 and T2-weighted sequences. A good correlation was
      observed between cognitive deficits and the location of the lesions in four
      patients. CONCLUSIONS: NPS may be the initial complaint in MS patients, often
      associated with other cognitive deficits, and it shows a close relationship with
      lesion location.

PMID- 24124778
TI  - Sexual metabolic differences in the rat limbic brain.
AB  - BACKGROUND: There is actually limited evidence about the influence of estrogens
      on neuronal energy metabolism or functional cerebral asymmetry. In order to
      evaluate this relationship, eight male and sixteen female adult Wistar rats,
      divided into estrus and diestrus phase, were used to measure basal neuronal
      metabolic activity in some of the structures involved in the Papez circuit, using
      cytochrome c oxidase (C.O.) histochemistry. METHOD: We used C.O. histochemistry
      because cytochrome oxidase activity can be considered as a reliable endogenous
      marker of neuronal activity. RESULTS: We found higher C.O. activity levels in
      diestrus as compared to estrus and male groups in the prefrontal cortex and
      thalamus. Conversely, neuronal oxidative metabolism was significantly higher in
      estrus than in diestrus and male groups in the dorsal and ventral hippocampus
      (CA1 and CA3) and in the mammillary bodies. However, no hemispheric functional
      lateralization was found in estrus, diestrus or male groups by C.O. activity.
      CONCLUSIONS: These results suggest a modulatory effect of estrogens on neuronal
      oxidative metabolism.

PMID- 24124779
TI  - Development of different spatial frames of reference for orientation in small
      scale environments.
AB  - BACKGROUND: Previous studies show that there is a developmental transition in the
      frames of reference children use to orientate from a body-centered to an
      allocentric strategy. However, there is no agreement concerning the age at which
      they begin to integrate and flexibly use both strategies in small-scale
      environments. METHOD: 6-10-year-old children and adults were trained to locate a
      hidden object in an arm-maze placed within a small-scale model, which maintained
      stable relationships with the frames of reference provided by the experimental
      room and by the subject (Experiment 1), and in a situation of inconsistency
      between the frame provided by the small-scale model and the other two (Experiment
      2). RESULTS: When the frames of reference provided by the room and by the subject
      conflict with that of the manipulative space, the performance deteriorates
      compared to the situation when multiple frames of reference can be used
      cooperatively to locate the goal. The flexible use of the information provided by
      the model (i.e., the cues surrounding the maze and the geometrical features)
      emerged at 10 years. CONCLUSIONS: Through development, children acquire new
      spatial abilities and increasing flexibility in the conjoint use of egocentric
      and allocentric frames of reference in small-scale environments.

PMID- 24124780
TI  - Phonological recovery in Spanish developmental dyslexics through the tip-of-the
      tongue paradigm.
AB  - BACKGROUND: Developmental dyslexics have difficulties accessing and retrieving
      the phonological form of words, in the absence of a deficit at the semantic
      level. The aim of this work was to study, through the Tip-of-the-tongue (TOT)
      paradigm, the problems of lexical access in Spanish-speaking developmental
      dyslexics and the relationship with their phonological awareness. METHOD: A group
      of developmental dyslexics (14) and other children without reading difficulties
      (14), aged 7 to 12, performed a picture naming task of medium and low frequency
      and a task of phonological awareness. RESULTS: The results indicated that
      dyslexic children generally show a greater number of TOT phenomena than the
      control group. Despite being able to provide semantic information of the drawing,
      they had difficulties retrieving partial phonological information. CONCLUSIONS:
      These results indicate that developmental dyslexic children have particular
      difficulty in accessing the phonological form of words, which may be interesting
      for the development of intervention programs for these children.

PMID- 24124781
TI  - Psychologists and child psychological maltreatment severity assessment.
AB  - BACKGROUND: Psychological maltreatment (PM) is probably the most difficult child
      maltreatment form to detect and evaluate. The objective of this research was to
      determine the effect of an instrument developed to improve accuracy in the
      assessment of PM severity in Child Protection Services (CPS). METHOD: Case
      vignettes representing different severity levels of PM situations were used. 146
      CPS psychologists participated in the study. A first group was made up of 115
      psychologists who had been trained in the use of the instrument for 4 hours. The
      second group was made up of 31 psychologists who had been using the instrument
      for more than 12 months at the time of the study. Psychologists from the first
      group rated the severity of the vignettes in two ways: applying their own daily
      work criteria and applying the instrument after the training. RESULTS: Accurate
      ratings clearly improved when psychologists used the instrument criteria.
      However, only psychologists who had used the instrument for more than 12 months
      at the time of the study obtained more than 80% of accurate ratings. CONCLUSIONS:
      Results support the importance for CPS psychologists to use psychological
      maltreatment severity assessment instruments and show the conditions under which
      they could be effective.

PMID- 24124782
TI  - Prevalence and risk factors of burnout syndrome among Spanish police officers.
AB  - BACKGROUND: Police work is currently one of the most stressful occupations. High
      levels of stress can culminate in suffering the burnout syndrome. This syndrome
      is characterised by emotional exhaustion, depersonalisation and low personal
      accomplishment. Police officers, despite being a risk group, have been
      investigated less than other professional groups. The objectives of the current
      work are to estimate the prevalence of burnout syndrome in police officers, to
      present a classification of the syndrome and to identify some risk factors (socio
      demographic, personality, and work-related). METHOD: A cross-sectional study was
      carried out with 747 national police officers from Andalucia (Spain). RESULTS:
      The prevalence of burnout is high. Furthermore, individual differences, and in
      particular, personality factors, are important to explain the development of
      burnout. CONCLUSIONS: Police officers are a risk group and, therefore, actions
      aimed at reducing the levels of burnout among these professionals should be
      developed.

PMID- 24124783
TI  - Distortions and gender-related differences in the perception of mechanical
      engineering in high school students.
AB  - BACKGROUND: The reason for this study was the low interest that high school
      students, particularly females, show for the subject of mechanical engineering
      (ME). We assumed that this problem was partly due to: (a) lack of understanding
      of the tasks involved in ME, and (b) a distorted and negative perception of the
      professional environment and working conditions. METHOD: To assess these two
      assumptions, two measurement instruments (tasks and perceptions) were developed
      and administered in a sample of 496 high school students. A multiple-group design
      was used and data was analyzed by using an extended item response theory model.
      RESULTS: In general terms, the results agreed with our expectations. However, no
      significant gender differences were found. DISCUSSION: The implications of the
      results for future improvements are discussed.

PMID- 24124784
TI  - Using the R-MAPE index as a resistant measure of forecast accuracy.
AB  - BACKGROUND: The mean absolute percentage error (MAPE) is probably the most widely
      used goodness-of-fit measure. However, it does not meet the validity criterion
      due to the fact that the distribution of the absolute percentage errors is
      usually skewed to the right, with the presence of outlier values. In these cases,
      MAPE overstates the corresponding population parameter. In this study, we propose
      an alternative index, called Resistant MAPE or R-MAPE based on the calculation of
      the Huber M-estimator, which allows overcoming the aforementioned limitation.
      METHOD: The results derived from the application of Artificial Neural Network
      (ANN) and Autoregressive Integrated Moving Average (ARIMA) models are used to
      forecast a time series. RESULTS: The arithmetic mean, MAPE, overstates the
      corresponding population parameter, unlike R-MAPE, on a set of error
      distributions with a statistically significant right skew, as well as outlier
      values. CONCLUSIONS: Our results suggest that R-MAPE represents a suitable
      alternative measure of forecast accuracy, due to the fact that it provides a
      valid assessment of forecast accuracy compared to MAPE.

PMID- 24124785
TI  - The role of gender identity in adolescents' antisocial behavior.
AB  - BACKGROUND: Analysis of the relevance of the variables sex and gender to explain
      delinquency is a topic of growing interest in Criminology. This study tests a
      model of juvenile delinquency that integrates gender identity, the association
      with deviant peers, and a lack of attachment to conventional contexts. METHOD: We
      used a sample of 970 adolescents of both sexes, representative of the urban
      population, between 12 and 18 years, attending public schools in Galicia (Spain).
      RESULTS: The results of path analysis confirm that: a) weak attachment to
      conventional contexts, and belonging to a deviant groups are precedents for
      deviation of adolescents of both sexes; b) these contexts also contribute to the
      development of gender identity; and c) gender identity affects the likelihood of
      deviation: femininity tends to reduce this behavior, and masculinity (in
      particular, negatively valued masculinity) contributes to increase it.
      CONCLUSIONS: These findings support the adequacy of including gender identity in
      the explanatory models of delinquency. They also suggest the need to reconsider
      the role of conventional settings in the socialization of masculinity and,
      therefore, in the genesis of adolescent delinquency of both sexes.

PMID- 24124786
TI  - Comparison of self-reported attachment in young adults from Spain and the United
      States.
AB  - BACKGROUND: Previous studies have provided mixed evidence in support of the
      structure of Bartholomew's attachment framework. The current study examined the
      comparability of the correlations among the attachment prototypes as well as the
      underlying factor structure of the Relationship Questionnaire in independent
      samples of Spanish and American young adults. METHOD: Participants were 547
      students from the Universitat Autonoma de Barcelona and 1425 from the University
      of North Carolina at Greensboro who completed the Relationship Questionnaire.
      RESULTS: Secure attachment was negatively correlated with fearful attachment, as
      was preoccupied attachment with dismissing attachment. The secure-fearful
      association in the American sample represented a medium effect size, whereas the
      remaining correlations represented small effect sizes. Except for the secure
      fearful association, the correlations among prototypes were comparable in
      magnitude across samples. A principal components analysis yielded two factors
      that explained similar amounts of variance in the two samples. The pattern of
      loadings was relatively comparable in both samples; however, it was not entirely
      consistent with the theoretical model. CONCLUSIONS: The findings provided only
      partial support to the structure of the theoretical framework invoked. We discuss
      an alternative interpretation of the two factors, as well as further measurement
      considerations and directions for future research.

PMID- 24124787
TI  - Multilevel bootstrap analysis with assumptions violated.
AB  - BACKGROUND: Likelihood-based methods can work poorly when the residuals are not
      normally distributed and the variances across clusters are heterogeneous. METHOD:
      The performance of two estimation methods, the non-parametric residual bootstrap
      (RB) and the restricted maximum likelihood (REML) for fitting multilevel models
      are compared through simulation studies in terms of bias, coverage, and
      precision. RESULTS: We find that (a) both methods produce unbiased estimates of
      the fixed parameters, but biased estimates of the random parameters, although the
      REML was more prone to give biased estimates for the variance components; (b) the
      RB method yields substantial reductions in the difference between nominal and
      actual confidence interval coverage, compared with the REML method; and (c) for
      the square root of the mean squared error (RMSE) of the fixed effects, the RB
      method performed slightly better than the REML method. For the variance
      components, however, the RB method did not offer a systematic improvement over
      the REML method in terms of RMSE. CONCLUSIONS: It can be stated that the RB
      method is, in general, superior to the REML method with violated assumptions.

PMID- 24124788
TI  - Spanish adaptation of the Expectancy Questionnaire (EQ) about alcohol effects in
      adolescents.
AB  - BACKGROUND: Alcohol-related expectancies are especially relevant in relation to
      alcohol consumption during adolescence. The main aim of this study was to adapt
      and translate into Spanish (Castilian) the Expectancy Questionnaire (EQ), and to
      study its psychometric properties in adolescents. METHOD: The sample was composed
      of 514 adolescents (57.20% female, mean age = 15.21; SD = .63) who completed the
      EQ and the alcohol consumption questionnaire AIS-UJI. RESULTS: Confirmatory
      factor analysis indicated that an eight-factor model, grouped into two general
      factors of positive and negative expectancies, had acceptable fit indices.
      Cronbach's alphas ranged from .75 to .96. Finally, the structural equation model
      showed that positive expectancies were positively related to alcohol use, whereas
      negative expectancies were negatively related to drinking. CONCLUSIONS: Results
      showed that the Spanish version of the EQ for adolescents is a valid and reliable
      questionnaire to measure expectancies about alcohol effects.

PMID- 24124789
TI  - Psychometric properties of the Dyadic Adjustment Scale (DAS) in a community
      sample of couples.
AB  - BACKGROUND: This study analyzed the psychometric properties of the Dyadic
      Adjustment Scale (DAS). METHOD: A sample of 1,180 participants, 590 adult
      heterosexual couples, from the Community of Madrid was examined via confirmatory
      factor analysis. RESULTS: The results indicate that the factor structure of this
      scale fits the hierarchical factor model proposed by the test authors. The
      internal consistency, estimated using Cronbach's alpha coefficient was
      satisfactory for the total scale (alpha = .80) and ranged from .13 to .88 for the
      subscales. Convergent validity was adequate in comparison to the Negotiation
      subscale (emotional and cognitive) from the Revised Conflict Tactics Scales
      (CTS2). No significant differences were observed between genders. Finally,
      concordance or agreement between partners was high. The lowest agreement was
      found for the Affectional Expression subscale. CONCLUSIONS: After examining the
      psychometric properties, the DAS was found to be a reliable and valid measurement
      of the sampled community of couples.

PMID- 24124790
TI  - Psychometrical properties of the "How I Think" Questionnaire (HIT-Q) in
      adolescents.
AB  - BACKGROUND: The How I Think Questionnaire (HIT-Q) was developed to measure the
      main categories of self-serving cognitive distortions. METHOD: The present study
      analyses the psychometric properties of the HIT-Q Spanish-Version. The sample
      consisted of 1.490 Spanish-speaking adolescents recruited from various schools in
      Madrid (Spain). The participants had a mean age of 15.37 years (SD = 1.67).
      RESULTS: Confirmatory factor analyses (CFA) showed that the underlying structure
      of the HIT-Q was best explained by a six-factor solution (Self-Centred, Blaming
      Others, Minimizing/Mislabelling, Assuming the Worst, Anomalous Responses and
      Positive Fillers). CONCLUSIONS: After examination of its psychometric properties,
      it was concluded that the Spanish version of the HIT-Q is a reliable and valid
      measure of self-serving cognitive distortions in Spanish adolescents.

PMID- 24124791
TI  - Validation of the English version of the Five-Factor Self-Concept Questionnaire.
AB  - BACKGROUND: The Spanish Five-Factor Self-Concept Questionnaire (AF5) is one of
      the most widely used instruments assessing self-concept with Spanish-speaking
      samples. It is also one of the few psychometrically sound instruments assessing
      self-concept from a multidimensional perspective. The availability of the AF5 in
      both languages (Spanish and English) would expand its potential, and would
      facilitate cross-cultural research. METHOD: To validate the English version of
      the AF5, we used multi-sample confirmatory factor analysis. The sample was 624
      USA respondents, 301 males (48%) and 323 females, ranging in age from 14 to 18 (M
      = 16.21, SD = 1.08). RESULTS: The English version of the AF5 does not change the
      original factor weights, the variances and covariances of the factors, or the
      error variances of items, with regard to the original Spanish five-factor model.
      The five factors proposed -academic, social, emotional, family, and physical-
      satisfactorily reproduce the inter-item relationships of the original Spanish
      version. The reliability for all items and dimensions of the English version was
      also good, with similar results as the original version. CONCLUSIONS: This
      preliminary validation study of the English version of the AF5 showed that it is
      an acceptable measure to be used with English-speaking adolescents.

PMID- 24124792
TI  - Variation in vertebral number and its morphological implication in Galaxias
      platei.
AB  - Variation in the vertebral number of the puyen grande Galaxias platei was
      examined for specimens from 22 localities that span the entire distribution range
      of the species (from 40 degrees  to 55 degrees  S). The mean vertebral number
      (NMW ) increases towards high latitudes, i.e. Jordan's rule is applicable to this
      species. Owing to the wide geographic variation of the species, not only in
      latitude but also in altitude, the most explicative variable for NMW was mean
      winter air temperature, showing negative dependence. Morphological data suggest
      that the increment in vertebral number lies in the pre-pelvic region of the trunk
      and in the caudal region, but not in the segment between pelvic-fin insertion and
      the origin of the anal fin. As these alterations in body shape have important
      consequences for hydrodynamics and swimming performance, vertebral number
      variation in G. platei also holds implications for both individual and population
      fitness. 

PMID- 24124793
TI  - Uniform zinc oxide nanowire arrays grown on nonepitaxial surface with general
      orientation control.
AB  - Bottom-up synthesis of zinc oxide (ZnO) nanowires requires a highly engineered
      substrate to achieve alignment and orientation control. Here, we report textured
      ZnO film as an inexpensive substrate to fulfill the requirement. The textured
      film is coated conformally on various surface topographies and allows the
      epitaxial growth of ZnO nanowires with vertical, tilted, or lateral orientations.
      The textured film can also be formed into three-dimensional structure for growing
      novel nanostructures. The growth flexibility can potentially simplify device
      fabrication and optimize device performance. 

PMID- 24124795
TI  - Changing epidemiology of Powassan encephalitis in North America suggests the
      emergence of the deer tick virus subtype.

PMID- 24124794
TI  - Novel carvedilol analogues that suppress store-overload-induced Ca2+ release.
AB  - Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias
      in patients with heart failure. This activity is in part because of its ability
      to inhibit store-overload-induced calcium release (SOICR) through the RyR2
      channel. We describe the synthesis, characterization, and bioassay of ca. 100
      compounds based on the carvedilol motif to identify features that correlate with
      and optimize SOICR inhibition. A single-cell bioassay was employed on the basis
      of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the
      endoplasmic reticulum through the defective channel was measured. IC50 values for
      SOICR inhibition were thus obtained. The compounds investigated contained
      modifications to the three principal subunits of carvedilol, including the
      carbazole and catechol moieties, as well as the linker chain containing the beta
      amino alcohol functionality. The SAR results indicate that significant
      alterations are tolerated in each of the three subunits. 

PMID- 24124797
TI  - Halting and reversing HIV epidemics in Asia by interrupting transmission in sex
      work: experience and outcomes from ten countries.
AB  - HIV epidemics spread rapidly through Asian sex work networks two decades ago
      under conditions of high vulnerability, low condom use, intact male foreskins and
      ulcerative STIs. Experiences implementing interventions to prevent transmission
      in sex work in ten Asian countries were reviewed. All report increasing condom
      use trends in sex work. In the seven countries where condom use exceeds 80%,
      surveillance and other data indicate declining HIV trends or low and stable HIV
      prevalence with declining STI trends. All four countries with national-level HIV
      declines among sex workers have also documented significant HIV declines in the
      general population. While all interventions in sex work included outreach, condom
      programing and STI services, the largest declines were found in countries that
      implemented structural interventions on a large scale. Thailand and Cambodia,
      having controlled transmission early, are closest to providing universal access
      to HIV care, support and treatment and are exploring HIV elimination strategies. 

PMID- 24124798
TI  - Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative
      patients: the evidence.
AB  - Pulmonary disease (PD) caused by nontuberculous mycobacteria is an emerging
      infection mainly in countries where the incidence of tuberculosis is in decline.
      It affects an elderly population, often with underlying chronic lung diseases,
      but its epidemiology shows significant regional variation. Guidelines and
      recommendations for treatment of these infections exist, but build strongly on
      expert opinion, as very few good quality clinical trials have been performed in
      this field. Only for the most frequent causative agents, the Mycobacterium avium
      complex, Mycobacterium kansasii and Mycobacterium abscessus, a reasonable number
      of trials and case series is now available. For the less frequent causative
      agents of pulmonary nontuberculous mycobacterial (NTM) disease (Mycobacterium
      xenopi, Mycobacterium malmoense, Mycobacterium fortuitum, Mycobacterium chelonae)
      data is mostly limited to a few very small case series. Within this review, we
      have collected and combined evidence from all available trials and case series.
      From the data of these trials and case series, we reconstruct a more evidence
      based overview of possible drug treatment regimens and their outcomes. 

PMID- 24124799
TI  - Oral inflammation, a role for antimicrobial peptide modulation of cytokine and
      chemokine responses.
AB  - Acute and chronic inflammation commonly occurs throughout the oral cavity. The
      most common causes are physical damage and microbial infections, and less
      frequently immune reactions and malignant changes. All of these processes result
      in the induction of antimicrobial peptides, chemokines and cytokines that lead to
      cellular infiltrates, a vascular response, tissue destruction and cellular
      proliferation. A fascinating concept developing in the current literature
      suggests that antimicrobial peptides modulate the production of chemokines,
      cytokines and other cellular mediators and that this may have a larger
      ramification as an underlying mechanism mediating inflammation. Here, we propose
      that the ability of antimicrobial peptides to induce chemokines and anti
      inflammatory or proinflammatory cytokines plays an important role in the early
      events of oral inflammation and may be a target for the prevention or treatment
      of oral inflammatory conditions. 

PMID- 24124800
TI  - Macular cherry-red spot helps diagnose rare storage disorder in an infant with
      repeated respiratory tract infections: case report.
AB  - A seven-month-old male child was brought in for an eye test for poor vision and
      nystagmus noticed from four months of age. The child had delayed milestones of
      development and multiple (six times) episodes of unexplained lower respiratory
      tract infection (from two months of age) treated by pediatricians at different
      centers without complete cure. Fundus examination showed bilateral cherry-red
      spots at the macula. There were diffusely distributed hyper-pigmented patches
      (Mongolian spots) on the back and extensor aspect of the extremities. The case
      was sent back to the pediatricians for a re-evaluation to rule out storage
      disorder. Lysosomal enzyme assay in the leucocytes showed a significantly reduced
      beta-galactosidase level (15.6 nmol/hr/mg protein in contrast to a normal range
      of 79.6 to 480.0). This confirmed the patient to be a case of lysosomal storage
      disease, the GM1 gangliosidosis (type I).

PMID- 24124801
TI  - Effect of distilled water on rapid inactivation of tumour cells attached to
      surgery instruments.
AB  - The aim of the study was to explore the effect of distilled water on killing
      tumour cells attached to the surgery instruments during operation. Tumour cells
      were collected from the suspected tumour cell-contaminated surgery instruments
      and then cultured. Then the tumour cells were treated by distilled water at
      different gradient temperature for different time periods. The morphology of the
      tumour cells was observed by inverted microscope after hematoxylin-eosin
      staining. The results showed that positive tumour cell culture rate was 34.3%.
      After soaked in distilled water for 60 s at 55 degrees C, the tumour cells were
      inactive, and the death rate was 100%. We also found that no active cells were
      seen to grow adherently after recultured. In conclusion, tumour cells can be
      killed by distilled water for 60 s at 55 degrees C, which provides a new fast and
      low-cost tumour-free technique to inactivate tumour cells attached to surgery
      instruments. 

PMID- 24124802
TI  - Osteoporotic rat models for evaluation of osseointegration of bone implants.
AB  - Osseointegration of dental and orthopedic bone implants is the important process
      that leads to mechanical fixation of implants and warrants implant functionality.
      In view of increasing numbers of osteoporotic patients, bone implant surface
      optimization strategies with instructive and drug-loading ability have been
      heavily explored. However, few animal models are available to study the effect of
      novel implant surface modifications in osteoporotic conditions. Since laboratory
      rats comply with a number of practical advantages, including the reliability of
      several methods for rapid induction of osteoporotic conditions, the present work
      aimed to define the use of the femoral condyle in osteoporotic female and male
      rats as a suitable implantation model to study osseointegration of bone implants.
      The method describes the procedures for induction (by hypogonadism) and
      assessment (by in vivo micro-computed tomography [CT]) of osteoporotic conditions
      in both female and male rats. The implantation site architecture (femoral condyle
      bone properties and dimensions) was comparatively evaluated for female and male
      rats, and the implant installation procedures are described. Finally, the
      possible analytical techniques to evaluate bone responses via mechanical tests,
      ex vivo micro-CT, and histological methods are provided. 

PMID- 24124803
TI  - Characteristics and contributing factors related to sports injuries in young
      volleyball players.
AB  - BACKGROUND: The participation of young in volleyball is becoming increasingly
      common, and this increased involvement raises concerns about the risk of
      installation of sports injuries. Therefore, the objectives the study were
      identify the characteristics of sports injuries in young volleyball players and
      associate anthropometric and training variables with contributing factors for
      injuries. METHODS: A total of 522 volleyball players participating in the High
      School Olympic Games of the State of Sao Paulo (Brazil) were interviewed. A
      reported condition inquiry was used to gather information on injuries, such as
      anatomic site affected, mechanism and moment of injury, as well as personal and
      training data. The level of significance was set at 5%. RESULTS: A 19% frequency
      of injuries was found. Higher age, weight, height, body mass index and training
      duration values were associated with the occurrence of injuries. The most
      affected anatomic site was the ankle/foot complex (45 injuries, 36.3%). Direct
      contact and contactless mechanisms were the main causes of injuries (61 injuries;
      49.2% and 48 injuries; 38.7%, respectively). Training was the moment in which
      most injuries occurred (93 injuries; 75%), independently of personal and training
      characteristics. CONCLUSION: Injuries affected the ankle/foot complex with a
      greater frequency. Direct contact and contactless mechanisms were the most
      frequently reported and injuries occurred mainly during training sessions.
      Personal and training characteristics were contributing factors for the
      occurrence of injuries.

PMID- 24124804
TI  - The influence of alkaline earth metal equilibria on the rheological, melting and
      textural properties of Cheddar cheese.
AB  - The total calcium content of cheese, along with changes in the equilibrium
      between soluble and casein (CN)-bound calcium during ripening can have a major
      impact on its rheological, functional and textural properties; however, little is
      known about the effect of other alkaline earth metals. NaCl was partially
      substituted with MgCl2 or SrCl2 (8.7 and 11.4 g/kg curd, respectively) at the
      salting stage of cheesemaking to study their effects on cheese. Three cheeses
      were produced: Mg supplemented (+Mg), Sr supplemented (+Sr) and a control Cheddar
      cheese. Ca, Mg and Sr contents of cheese and expressible serum obtained therefrom
      were determined by atomic absorption spectroscopy. Addition of Mg2+ or Sr2+ had
      no effect on % moisture, protein, fat and extent of proteolysis. A proportion of
      the added Mg2+ and Sr2+ became CN-bound. The level of CN-bound Mg was higher in
      the +Mg cheese than the control throughout ripening. The level of CN-bound Ca and
      Mg decreased during ripening in all cheeses, as did % CN-bound Sr in the +Sr
      cheese. The presence of Sr2+ increased % CN-bound Ca and Mg at a number of
      ripening times. Adding Mg2+ had no effect on % CN-bound Ca. The +Sr cheese
      exhibited a higher G' at 70  degrees C and a lower LTmax than the control and +Mg
      cheeses throughout ripening. The +Sr cheese had significantly lower meltability
      compared with the control and +Mg cheeses after 2 months of ripening. Hardness
      values of the +Sr cheese were higher at week 2 than the +Mg and control cheeses.
      Addition of Mg2+ did not influence the physical properties of cheese.
      Supplementing cheese with Sr appeared to have effects analogous to those
      previously reported for increasing Ca content. Sr2+ may form and/or modify
      nanocluster crosslinks causing an increase in the strength of the para-casein
      matrix. 

PMID- 24124805
TI  - Photophysical properties of substituted homoleptic and heteroleptic
      phenylimidazolinato Ir(III) complexes as a blue phosphorescent material.
AB  - Iridium complexes are one of the most important materials for fabrication of
      organic light emitting diodes (OLEDs). There are difficulties in the preparation
      of blue phosphorescent complexes with respect to chromaticity, emission
      efficiency, and stability of the material, compared with green and red
      phosphorescent complexes. Control of the frontier orbital energy level (HOMO
      LUMO) is the sole method to achieve better blue phosphorescent iridium complexes
      by appropriate ligand selection and the introduction of adequate substituents.
      Homoleptic and heteroleptic iridium(III) tris(phenylimidazolinate) complexes were
      synthesized, and the effect of the substituents on their nature in the excited
      state was examined. Density functional theory calculation showed that the
      imidazolinato complexes have the HOMO localized at the iridium d- and phenyl pi
      orbitals. The LUMO is also localized on the phenyl moiety with a much higher
      population than HOMO. This LUMO is quite different from other complexes, such as
      iridium(III) tris(phenylpyridinate) and tris(phenylpyrazolinate) complexes.
      Therefore, substitution with pi-electron donating groups and electron withdrawing
      groups induces blue and red spectral shifts, respectively, which is the reverse
      shift exhibited by other complexes. The ancillary ligand (acetylacetone) acts as
      a path for nonradiative deactivation in the blue phosphorescent complexes. 

PMID- 24124806
TI  - Excimer luminescence from nonresonantly excited pyrene and perylene molecules in
      solution.
AB  - By nonresonant excitation below the absorption edge of pyrene and perylene
      molecules in solution, efficient excimer luminescence is observed. For perylene
      in solution, there are two kinds of nonresonant excimer emission that closely
      resemble Y- and E-emissions in perylene crystal and perylene in polymer. The
      concentration dependence of the photon flux density of monomer and excimer
      emission is reasonably explained by a simple model with a few fitting parameters
      based on the ordinary excimer formation process, in which the excited-state
      monomer interacts with a ground-state monomer. Observed quantum efficiency of
      excimer formation is by orders of magnitude higher than that expected if a
      monomer is excited from thermally populated vibrational levels. The experimental
      evidence for direct resonant excitation of excimers in perylene nanocrystals is
      obtained from the absence of anti-Stokes emission. This is due to a symmetry
      breaking effect close to crystal surface, suggesting that excimers are formed
      through a more efficient process in solution, such as resonant excitation of
      weakly interacting molecules with a symmetry-broken intermolecular configuration.

PMID- 24124807
TI  - The ethics of "Top Doctor" awards: a tangled web.

PMID- 24124808
TI  - Expedited partner therapy for scabies: legal and ethical considerations.

PMID- 24124809
TI  - Topical treatments for chronic plaque psoriasis: an abridged Cochrane systematic
      review.
AB  - BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis and is
      characterized by redness, thickness, and scaling. First-line management is with
      topical treatments. OBJECTIVE: We sought to undertake a Cochrane review of
      topical treatments for chronic plaque psoriasis. METHODS: We systematically
      searched major databases for randomized controlled trials. Trials reported
      improvement using a range of related measures; standardized, pooled findings were
      translated onto a 6-point improvement scale. RESULTS: The review included 177
      randomized controlled trials with 34,808 participants, including 26 trials of
      scalp psoriasis and 6 trials of inverse and/or facial psoriasis. Typical trial
      duration was 3 to 8 weeks. When compared with placebo (emollient base), the
      average improvement for vitamin-D analogues and potent corticosteroids was
      approximately 1 point, dithranol 1.2 points, very potent corticosteroids 1.8
      points, and combined vitamin-D analogue plus steroid 1.4 points once daily and
      2.2 points twice daily. However, these are indicative benefits drawn from
      heterogeneous trial findings. Corticosteroids were more effective than vitamin D
      for treating psoriasis of the scalp. For both body and scalp psoriasis, potent
      corticosteroids were less likely than vitamin D to cause skin irritation.
      LIMITATIONS: Reporting of benefits, adverse effects, and safety assessment
      methods was often inadequate. In many comparisons, heterogeneity made the size of
      treatment benefit uncertain. CONCLUSIONS: Corticosteroids are as effective as
      vitamin-D analogues and cause less skin irritation. However, further research is
      needed to inform long-term maintenance treatment and provide appropriate safety
      data.

PMID- 24124810
TI  - Improving outcomes for harlequin ichthyosis.

PMID- 24124811
TI  - Reducing cognitive errors in dermatology: can anything be done?
AB  - An increasing focus on the prevention of medical errors is a direct result of a
      growing patient safety movement. Although the reduction of technical errors has
      been the focus of most interventions, cognitive errors, usually more than one
      error linked together, actually cause the majority of misdiagnoses. This article
      examines the most common types of cognitive errors in dermatology. Two methods to
      minimize these errors are recommended: first, cognitive debiasing techniques
      reduce the common initiating factor of error cascades; and secondly, the
      application of prospective hindsight attacks the final common pathway that leads
      to misdiagnosis. 

PMID- 24124812
TI  - Current status of dermoscopy in the diagnosis of dermatologic disease.

PMID- 24124813
TI  - Improving students' ability to perform skin examinations and detect cutaneous
      malignancies using standardized patients and moulage.

PMID- 24124814
TI  - Comments on: "are there moral obligations to cosmetic dermatology patients beyond
      informed consent?".

PMID- 24124815
TI  - Reply to letter to the editor: "are there moral obligations to cosmetic
      dermatology patients beyond informed consent?".

PMID- 24124816
TI  - Counterpoint: analysis of patient claims data to determine the prevalence of
      hidradenitis suppurativa in the United States.

PMID- 24124817
TI  - Analysis of patient claims data to determine the prevalence of hidradenitis
      suppurativa in the United States.

PMID- 24124818
TI  - The USB microscope--a new tool for dermatologic imaging?

PMID- 24124819
TI  - Barriers to mobile teledermoscopy in primary care.

PMID- 24124820
TI  - Clinical features of vitiligo associated with comorbid autoimmune disease: a
      prospective survey.

PMID- 24124821
TI  - Large lymphatic vessel density in primary malignant melanoma predicts sentinel
      node status.

PMID- 24124822
TI  - A novel hydrogel scaffold for the prevention or reduction of the recurrence of
      keloid scars postsurgical excision.

PMID- 24124823
TI  - Lichen planopilaris treated by the peroxisome proliferator activated receptor
      gamma agonist pioglitazone: lack of lasting improvement or cure in the majority
      of patients.

PMID- 24124824
TI  - Anti-IgE therapy and severe atopic dermatitis: a pediatric perspective.

PMID- 24124825
TI  - A pilot study evaluating the efficacy of botulinum toxin A in the treatment of
      Raynaud phenomenon.

PMID- 24124826
TI  - The relationship between motor neuron disease and bullous pemphigoid: an English
      cohort study.

PMID- 24124827
TI  - The use of digital cameras by US dermatologists.

PMID- 24124828
TI  - Adverse cutaneous reactions to the new second-generation tyrosine kinase
      inhibitors (dasatinib, nilotinib) in chronic myeloid leukemia.

PMID- 24124829
TI  - Assessment of interleukin-17 and vitamin D serum levels in psoriatic patients.

PMID- 24124830
TI  - Partner involvement in conduct of skin self-examinations remains low following
      CDKN2A/p16 genetic test reporting and counseling.

PMID- 24124831
TI  - JAAD Grand Rounds quiz: a 42-year-old woman with stage IIIC melanoma treated with
      ipilimumab.
AB  - Instructions: In answering each question, refer to the specific directions
      provided. Because it is often necessary to provide information occurring later in
      a series that give away answers to earlier questions, please answer the questions
      in each series in sequence. 

PMID- 24124832
TI  - JAAD Grand Rounds quiz: nail dystrophy and multiple hyperkeratotic papules on the
      face and neck.

PMID- 24124834
TI  - Obtaining rapid and effective hemostasis: Part I. Update and review of topical
      hemostatic agents.
AB  - Effective and rapid hemostasis is critical to optimize surgical outcomes. An
      advantageous adjunct in accelerating the clotting process during dermatologic
      surgery is the use of topical hemostatic agents, which allow dermatologic
      surgeons to quickly clear the surgical field while avoiding the adverse effects
      of systemic medications. The growing rate of patients with pacemakers and
      defibrillators limits the possibility of electrosurgery. It is not unusual for
      patients to be taking >=1 anticoagulant medication(s). For these reasons, the use
      of topical hemostatic agents is likely to gain more recognition in the
      literature. The term topical hemostatic agents encompasses an array of
      pharmacotherapies, sealants, adhesives, absorbable agents, biologics, and
      combination products. The optimal use of topical hemostatic agents demands that
      dermatologic surgeons be familiar with each of these options, because the type of
      product used must be selected based on surgical location, wound size, and the
      extent of bleeding. With few randomized controlled trials in existence reviewing
      the efficacy of these medications, the subject of topical styptic agents has
      largely gone unstudied. Part I of this continuing medical education article
      reviews the available topical hemostatic agents and the ideal clinical settings
      for their use.

PMID- 24124833
TI  - JAAD Grand Rounds quiz: enlarging scalp nodule in an elderly woman.

PMID- 24124835
TI  - Obtaining rapid and effective hemostasis: Part II. Electrosurgery in patients
      with implantable cardiac devices.
AB  - Electrosurgery is an integral part of dermatology that is commonly used both to
      obtain hemostasis and to treat cutaneous lesions. However, it can cause many
      complications in patients with implantable devices. Because of the risk of
      electromagnetic interference, a variety of precautions are commonly used. Not
      only are there no consistent community-based standards in place regarding the
      performance of electrosurgery in patients with implantable devices, but these
      precautions are largely based upon anecdotal experience or recommendations from
      different specialties. To further complicate matters, the literature regarding
      electrosurgery use in patients with implantable cardiac devices is limited,
      especially with respect to dermatologic surgery. As the use of implantable
      cardiac devices continues to grow, our ability to care for patients with
      implantable devices must expand. Part II of this continuing medical education
      article discusses the current recommendations for using electrosurgery in
      patients with implantable cardiac devices during dermatologic procedures. 

PMID- 24124838
TI  - Dermoscopic subpatterns of granulomatous skin diseases.

PMID- 24124839
TI  - Spoke wheel-like structures in superficial basal cell carcinoma: a correlation
      between dermoscopy, histopathology, and reflective confocal microscopy.

PMID- 24124840
TI  - Facial pruritus.

PMID- 24124841
TI  - Melanoma at the periphery of a congenital melanocytic nevus.

PMID- 24124842
TI  - Pigmented macule on the tongue of a 12-year-old girl.

PMID- 24124843
TI  - Dermoscopy and confocal microscopy clues in the diagnosis of psoriasis and
      porokeratosis.

PMID- 24124844
TI  - Multiple pigmented eccrine hidrocystomas within scars in a patient with recessive
      dystrophic epidermolysis bullosa.

PMID- 24124845
TI  - A disease of the present: scurvy in "well-nourished" patients.

PMID- 24124846
TI  - Cutaneous sarcoidal granuloma after botulinum toxin type A injection.

PMID- 24124847
TI  - Pityriasis rubra pilaris-like eruption associated with the multikinase inhibitor
      ponatinib.

PMID- 24124848
TI  - Disseminated histoplasmosis with hypercalcemia.

PMID- 24124849
TI  - Eruptive papular elastorrhexis of the face and scalp.

PMID- 24124850
TI  - A therapeutic trial of antituberculous therapy for suspected lupus vulgaris: How
      long does it take to see clinical improvement?

PMID- 24124851
TI  - Treatment of porokeratosis of Mibelli with cantharidin.

PMID- 24124852
TI  - Mycobacterium chelonae infection after laser hair removal.

PMID- 24124853
TI  - Somatic mosaicism of eccrine spiradenomas with malignant degeneration and distant
      metastases.

PMID- 24124854
TI  - Eruptive milia secondary to vemurafenib.

PMID- 24124855
TI  - Lupus erythematosus panniculitis-induced facial atrophy: effective treatment with
      poly-L-lactic acid and hyaluronic acid dermal fillers.

PMID- 24124856
TI  - Malignant perivascular epithelioid cell tumor: a case report of a cutaneous tumor
      on the cheek of a male patient.

PMID- 24124857
TI  - Bullous drug eruption in a patient with psoriasis after a test dose of
      methotrexate.

PMID- 24124858
TI  - A maculopapular-type eruption associated with deferasirox administration.

PMID- 24124859
TI  - Acute autoimmune thrombocytopenia and worsening of dermatomyositis after
      administration of clarithromycin.

PMID- 24124860
TI  - Focal and atrophic cutis marmorata telangiectatica congenita.

PMID- 24124861
TI  - Unilaterally dominant eosinophilic fasciitis after influenza vaccination.

PMID- 24124862
TI  - Intractable erythromelalgia of the lower extremities successfully treated with
      lumbar sympathetic block.

PMID- 24124863
TI  - Cutaneous and pulmonary sarcoidosis-like reaction associated with ipilimumab.

PMID- 24124864
TI  - Eccrine squamous syringometaplasia associated with dabrafenib therapy.

PMID- 24124865
TI  - Primary cutaneous plasmablastic lymphoma in an immunocompetent patient.

PMID- 24124866
TI  - Pityriasis folliculorum: a novel therapy for a diagnostically challenging
      condition.

PMID- 24124867
TI  - Modulating stepwise photochromism in platinum(II) complexes with dual
      dithienylethene-acetylides by a progressive red shift of ring-closure absorption.
AB  - To modulate stepwise photochromism by shifting ring-closure absorption of the
      dithienylethene (DTE) moiety, trans-Pt(PEt3)2(C=C-DTE)2 [C=C-DTE = L1o (1oo), L2o
      (2oo), L3o (3oo), and L4o (4oo)] and cis-Pt(PEt3)2(L4o)2 (5oo) with two identical
      DTE-acetylides were elaborately designed. With the gradual red shift of ring
      closure absorption for L1c (441 nm) -> L2c (510 nm) -> L3c (556 nm) -> L4c (602
      nm), stepwise photochromism is increasingly facilitated in trans-Pt(PEt3)2(C=C
      DTE)2 following 1oo -> 2oo -> 3oo -> 4oo. The conversion percentage of singly
      ring-closed 2co-4co to dually ring-closed 2cc-4cc at the photostationary state is
      progressively increased in the order 1cc (0%) -> 2cc (18%) -> 3cc (67%) -> 4cc
      (100%). Compared with trans-arranged 4oo, stepwise photochromism in the
      corresponding cis-counterpart 5oo is less pronounced, ascribed to either direct
      conversion of 5oo to 5cc or rapid conversion of 5co to 5cc. The progressively
      facile stepwise photocyclization following 2oo -> 3oo -> 4oo is reasonably
      interpreted by gradually enhanced transition character involving LUMO+1, which is
      the only unoccupied frontier orbital responsible for further photocyclization of
      singly ring-closed 2co-4co. 

PMID- 24124868
TI  - The impact of fraction magnitude knowledge on algebra performance and learning.
AB  - Knowledge of fractions is thought to be crucial for success with algebra, but
      empirical evidence supporting this conjecture is just beginning to emerge. In the
      current study, Algebra 1 students completed magnitude estimation tasks on three
      scales (0-1 [fractions], 0-1,000,000, and 0-62,571) just before beginning their
      unit on equation solving. Results indicated that fraction magnitude knowledge,
      and not whole number knowledge, was especially related to students' pretest
      knowledge of equation solving and encoding of equation features. Pretest fraction
      knowledge was also predictive of students' improvement in equation solving and
      equation encoding skills. Students' placement of unit fractions (e.g., those with
      a numerator of 1) was not especially useful for predicting algebra performance
      and learning in this population. Placement of non-unit fractions was more
      predictive, suggesting that proportional reasoning skills might be an important
      link between fraction knowledge and learning algebra. 

PMID- 24124869
TI  - Immune responses to hair dyes containing toluene-2,5-diamine.
AB  - BACKGROUND: Toluene-2,5-diamine (PTD) is the most frequently used dye in
      oxidative hair dyes on the Scandinavian market. However, little is known about
      immune responses to PTD-containing oxidative hair dyes. OBJECTIVES: To study
      immune responses induced by PTD-containing hair dyes in mice. METHODS: Immune
      responses against two different permanent hair dye products containing 1.60%
      (w/w) and 0.48% (w/w) PTD within the colour gel, and various concentrations of
      pure PTD were studied. The local inflammatory response was measured by ear
      swelling and cell infiltration, and T- and B-cell infiltration and proliferation
      was determined in the draining lymph nodes. RESULTS: Concentration-dependent
      immune responses were seen to PTD both in the skin and draining lymph nodes. The
      hair dye containing 1.60% PTD induced strong local inflammation and caused T- and
      B-cell infiltration and proliferation as well as an increased number of
      regulatory T cells in the draining lymph nodes. In contrast, the hair dye
      containing 0.48% PTD induced skin inflammation but only minor responses in the
      draining lymph nodes. CONCLUSIONS: Consumer-available PTD-containing permanent
      hair dyes can be potent immune activators inducing both pro- and anti
      inflammatory responses. The outcome of the response is dependent on allergen
      dose, amount of additional allergens and exposure regime.

PMID- 24124871
TI  - Assay of total glutathione and glutathione disulphide in seminal plasma of male
      partners of couples presenting for a fertility evaluation.
AB  - A method is described here for the determination of total glutathione (TGSH) and
      glutathione disulphide (GSSG) in the seminal plasma of the male partners of
      couples requesting a fertility evaluation. A suitable sample preparation
      procedure prior to high-performance liquid chromatography analysis is discussed.
      After adequate sample preparation, the samples were derivatised with ortho
      phthaldialdehyde to form a stable, highly fluorescent tricyclic derivative.
      Reversed-phase column chromatography was used for the separation, and the
      effluent was monitored with a fluorescence detector at an excitation wavelength
      of 350 nm and an emission wavelength of 420 nm. The analytical performance of
      this method was satisfactory. The intra-assay and inter-assay coefficients of
      variation were below 10%. The recoveries were as follows: 94.1% (CV 2.3%) for
      TGSH and 93.2% (CV 4.0%) for GSSG. No significant differences were found in
      either TGSH or GSSG concentration between the smokers and nonsmokers (2.07 +/-
      1.28 MUm versus 1.56 +/- 1.20 MUm, P = 0.431 and 95 +/- 56 nm versus 112 +/- 138
      nm, P = 0.825). 

PMID- 24124872
TI  - New developments in cancer vaccines.

PMID- 24124873
TI  - Increasing immunogenicity of cancer vaccines to improve their clinical outcome.

PMID- 24124870
TI  - Non-coding-regulatory regions of human brain genes delineated by bacterial
      artificial chromosome knock-in mice.
AB  - BACKGROUND: The next big challenge in human genetics is understanding the 98% of
      the genome that comprises non-coding DNA. Hidden in this DNA are sequences
      critical for gene regulation, and new experimental strategies are needed to
      understand the functional role of gene-regulation sequences in health and
      disease. In this study, we build upon our HuGX ('high-throughput human genes on
      the X chromosome') strategy to expand our understanding of human gene regulation
      in vivo. RESULTS: In all, ten human genes known to express in therapeutically
      important brain regions were chosen for study. For eight of these genes, human
      bacterial artificial chromosome clones were identified, retrofitted with a
      reporter, knocked single-copy into the Hprt locus in mouse embryonic stem cells,
      and mouse strains derived. Five of these human genes expressed in mouse, and all
      expressed in the adult brain region for which they were chosen. This defined the
      boundaries of the genomic DNA sufficient for brain expression, and refined our
      knowledge regarding the complexity of gene regulation. We also characterized for
      the first time the expression of human MAOA and NR2F2, two genes for which the
      mouse homologs have been extensively studied in the central nervous system (CNS),
      and AMOTL1 and NOV, for which roles in CNS have been unclear. CONCLUSIONS: We
      have demonstrated the use of the HuGX strategy to functionally delineate non
      coding-regulatory regions of therapeutically important human brain genes. Our
      results also show that a careful investigation, using publicly available
      resources and bioinformatics, can lead to accurate predictions of gene
      expression.

PMID- 24124874
TI  - Cancer vaccines: 21st century approaches to harnessing an ancient modality to
      fight cancer.

PMID- 24124876
TI  - Live-attenuated bacteria as a cancer vaccine vector.
AB  - In the emerging field of active and specific cancer immunotherapy, strategies
      using live-attenuated bacterial vectors have matured in terms of academic and
      industrial development. Different bacterial species can be genetically engineered
      to deliver antigen to APCs with strong adjuvant effects due to their microbial
      origin. Proteic or DNA-encoding antigen delivery routes and natural bacterial
      tropisms might differ among species, permitting different applications. After
      many academic efforts to resolve safety and efficacy issues, some firms have
      recently engaged clinical trials with live Listeria or Salmonella spp. We
      describe here the main technological advances that allowed bacteria to become one
      of the most promising vectors in cancer immunotherapy. 

PMID- 24124877
TI  - Oncolytic vaccines.
AB  - Oncolytic viruses are ideal platforms for tumor vaccination because they can
      mediate the direct in situ killing of tumor cells that release a broad array of
      tumor antigens and alarmins or danger signals thereby cross-priming antitumor
      cytotoxic T lymphocytes (CTLs), which mediate the indirect killing of uninfected
      cells. The balance between the direct and indirect killing phases of oncolytic
      virotherapy is the key to its success and can be manipulated by incorporating
      various immunomodulatory genes into the oncolytic virus genome. Recently, the
      interim analysis of a large multicenter Phase III clinical trial for Talimogene
      laherparepvec, a granulocyte-macrophage colony stimulating factor-armed oncolytic
      herpes simplex virus, revealed significant improvement in objective response and
      durable response rates over control arm and a trend toward improved overall
      survival. Meanwhile, newer oncolytics are being developed expressing additional
      immunomodulatory transgenes to further enhance cross-priming and the generation
      of antitumor CTLs and to block the immunosuppressive actions of the tumor
      microenvironment. Since oncolytic vaccines can be engineered to kill tumor cells
      directly, modulate the kinetics of the antitumor immune response and reverse the
      immunosuppressive actions of the tumor, they are predicted to emerge as the
      preferred immunotherapeutic anticancer weapons of the future. 

PMID- 24124878
TI  - VLPs and particle strategies for cancer vaccines.
AB  - Effective delivery of tumor antigens to APCs is one of the key steps for
      eliciting a strong and durable immune response to tumors. Several cancer vaccines
      have been evaluated in clinical trials, based on soluble peptides, but results
      have not been fully satisfactory. To improve immunogenicity particles provide a
      valid strategy to display and/or incorporate epitopes which can be efficiently
      targeted to APCs for effective induction of adaptive immunity. In the present
      review, we report some leading technologies for developing particulate vaccines
      employed in cancer immunotherapy, highlighting the key parameters for a rational
      design to elicit both humoral and cellular responses. 

PMID- 24124879
TI  - Gluten contamination of naturally gluten-free flours and starches used by
      Canadians with celiac disease.
AB  - A large national investigation into the extent of gluten cross-contamination of
      naturally gluten-free ingredients (flours and starches) sold in Canada was
      performed. Samples (n = 640) were purchased from eight Canadian cities and via
      the internet during the period 2010-2012 and analysed for gluten contamination.
      The results showed that 61 of the 640 (9.5%) samples were contaminated above the
      Codex-recommended maximum level for gluten-free products (20 mg kg-1) with a
      range of 5-7995 mg kg-1. For the ingredients that were labelled gluten-free the
      contamination range (5-141 mg kg-1) and number of samples were lower (3 of 268).
      This picture was consistent over time, with approximately the same percentage of
      samples above 20 mg kg-1 in both the initial set and the subsequent lot. Looking
      at the total mean (composite) contamination for specific ingredients the largest
      and most consistent contaminations come from higher fibre ingredients such as soy
      (902 mg kg-1), millet (272 mg kg-1) and buckwheat (153 mg kg-1). Of the naturally
      gluten-free flours and starches tested that do not contain a gluten-free label,
      the higher fibre ingredients would constitute the greatest probability of being
      contaminated with gluten above 20 mg kg-1.

PMID- 24124880
TI  - Biocatalytic response of multi-layer assembled collagen/hyaluronic acid
      nanoengineered capsules.
AB  - Biodegradable hollow capsules filled with fluorescently labelled bovine serum
      albumin (BSA) as a model drug were prepared via layer-by-layer (LbL) self
      assembly of type-I collagen (COL) and hyaluronic acid (HA) using calcium
      carbonate micro-particles and co-precipitation method. Capsules loaded with
      fluorescein isothiocyanate (FITC)-BSA, tetramethylrhodamin isothiocyanate (TRITC)
      BSA or Alex-Fluor-488-BSA, respectively, were characterised before and after core
      removal using Confocal Laser Scanning Microscopy (CLSM), whilst the morphologies
      of individual hollow capsules were assessed using Atomic Force Microscopy (AFM).
      The sustained release of the encapsulated FITC-BSA protein was attained using
      enzymatic degradation of the capsule shells by collagenase. The released profile
      of the fluorescently-labelled BSA indicated that it could be successfully
      controlled by modulating the number of layers and/or by collagen crosslinking
      either before or after the capsule's assembly.

PMID- 24124881
TI  - Characterisation, cytotoxicity and apoptosis studies of methotrexate-loaded PLGA
      and PLGA-PEG nanoparticles.
AB  - Methotrexate (MTX) widely used in the treatments of various types of
      malignancies, but high toxicity and short plasma half-life have limited its use.
      This study was aimed at developing a polymeric drug delivery system for improving
      the therapeutic index of this potent drug. To achieve these goals, PLGA and PLGA
      PEG nanoparticles were prepared using the emulsification-solvent diffusion
      technique and were optimized for particle size and entrapment efficiency. The
      optimum loaded nanoparticles were evaluated by cytotoxicity and their ability to
      induce apoptosis compared to free drug by examining of caspase-3 activity. The
      results showed that optimized particles were 182 +/- 14 nm and 258 +/- 10 nm in
      size for PLGA-PEG and PLGA nanoparticles, respectively, with an entrapment
      efficiency of more than 51%. The cytotoxicity experiment showed that the
      nanoparticles were more effective than pure MTX and increase the activity of
      caspase-3 in MCF7 and AGS and A549 cell lines.

PMID- 24124882
TI  - Microencapsulation of mildronate in biodegradable and non-biodegradable polymers.
AB  - The extremely high hygroscopicity (solubility in water >=2 g/ml) of the
      pharmaceutical preparation mildronate defines specific requirements to both
      packaging material and storage conditions. To overcome the above mentioned
      inconveniences, microencapsulated form of mildronate was developed using
      polystyrene (PS) and poly (lactic acid) (PLA) as watertight coating materials.
      Drug/polymer interaction as well as influence of the microencapsulation process
      variables on microparticle properties was studied in detail. Water-in-oil-in
      water double emulsion technique was adapted and applied for the preparation of
      PS/mildronate microparticles with total drug load up to 77 %wt and PLA/mildronate
      microparticles with total drug load up to 80 %wt. The repeatability of the
      microencapsulation process was +/-4% and the encapsulation efficiency of the
      active ingredient reached 60 %wt. The drug release kinetics from the obtained
      microparticles was evaluated and it was found that drug release in vivo could be
      successfully sustained if polystyrene matrix has been used.

PMID- 24124883
TI  - Synthesis, characterisation and drug release properties of microspheres of
      polystyrene with aliphatic polyester side-chains.
AB  - A series of graft copolymers consisting of polystyrene backbone with
      biocompatible side chains based on (co)polymers of l-lactic acid and glycolic
      acid were synthesised by combination two controlled polymerisations, namely,
      nitroxide mediated radical polymerisation (NMRP) and ring opening polymerisation
      (ROP) with "Click" chemistry. The main goal of this work was to design new
      biodegradable microspheres using obtained graft copolymers for long-term
      sustained release of imatinib mesylate (IMM) as a model drug. The IMM loaded
      microspheres of the graft copolymers, polystyrene-g-poly(lactide-co-glycolide)
      (PS-g-PLLGA), polystyrene-g-poly(lactic acid) (PS-g-PLLA) and poly(lactic
      coglycolic acid) (PLLGA) were then prepared by a modified water-in-oil-in-water
      (w1/o/w2) double emulsion/solvent evaporation technique. The optimised
      microspheres were characterised by particle size, encapsulation efficiency, and
      surface morphology also; their degradation and release properties were studied in
      vitro. The degradation studies of three different types of microspheres showed
      that the PS backbone of the graft copolymers slows down the degradation rate
      compared to PLLGA.

PMID- 24124884
TI  - Encapsulation of poly(D,L-lactide) microparticles with polyelectrolyte
      multilayers for antigen delivery.
AB  - Poly(D,L-lactide) (PLA) microparticles containing the ovalbumin (OVA) model
      antigen were prepared by the double-emulsion and solvent evaporation method,
      followed by encapsulation with alternating layers of the polyelectrolytes,
      consisting of protamine sulfate and dextran sulfate of various molecular weights.
      The physicochemical properties, including particle size and zeta potentials, were
      characterised. Treatment of mouse macrophages with surface-modified PLA
      microparticles stimulated the generation of reactive oxygen species (ROS), such
      as hydrogen peroxide and superoxide, which was detected by the fluorescent
      probes, 2',7'-dichlorofluorescein diacetate (DCFH-DA) and hydroethidine (HE).
      Incubation of murine bone marrow-derived dendritic cells (BMDCs) with the
      encapsulated PLA microparticles enhanced the presentation of OVA soluble antigens
      in B3Z cells, an OVA-specific CD8(+) T cell hybridoma. Results obtained in this
      study demonstrated the potential use of polyelectrolyte-encapsulated
      biodegradable microparticles for delivery of soluble antigens to the antigen
      presenting cells and stimulation of effective antigen presentation in the context
      of class I major histocompatibility complex.

PMID- 24124885
TI  - Preparation and characterisation of andrographolide niosomes and its anti
      hepatocellular carcinoma activity.
AB  - OBJECTIVE: In this study, a novel andrographolide (AG) preparation formulation,
      niosomes, was prepared to improve the bioavailability and tissue distribution of
      AG. METHODS: The niosomal formulation of AG was prepared by film
      hydration/sonication method and tissue distribution was measured by liquid
      chromatography-mass spectrometry (LC-MS) method in mice, and anti-hepatocellular
      carcinoma (anti-HCC) activity was examined by MTT method in HepG2. RESULTS:
      Entrapment efficiency, drug-loading ratio and average particle size of AG
      niosomes were 72.36%, 5.90% and 206 nm, respectively. The tissue distribution in
      mice demonstrated that the AG niosomes were absorbed in liver much more than the
      free AG. Furthermore, the anti-HCC activity in HepG2 cells showed that there was
      no significant difference between free AG and AG niosomes. CONCLUSION: The
      present results suggest that AG niosomes may have a significant potential of
      liver targeting, which is valuable in chemotherapy of HCC.

PMID- 24124886
TI  - Artificial oxygen carriers based on perfluorodecalin-filled poly(n-butyl
      cyanoacrylate) nanocapsules.
AB  - Poly(n-butyl-cyanoacrylate)-nanocapsules filled by perfluorodecalin (PFD) are
      proposed as potential oxygen carriers for blood substitute. The capsule
      dispersion is prepared via interfacial polymerisation from a PFD emulsion in
      water which in turn is generated by spontaneous phase separation. The resulting
      dispersion is capable of carrying approximately 10% of its own volume of gaseous
      oxygen, which is approximately half of the capacity of human blood. The volumes
      of the organic solvents and water are varied within a wide range, connected to a
      change of the capsule radius between 200 and 400 nm. The principal suitability of
      the capsule dispersion for intravenous application is proven in first
      physiological experiments. A total amount of 10 ml/kg body weight has been
      infused into rats, with the dispersion supernatant and a normal saline solution
      as controls. After the infusion of nanocapsules, the blood pressure as well as
      the heart rate remains constant on a normal level.

PMID- 24124887
TI  - Effect of nonionic compound emulsifiers Tween80 and Span80 on the properties of
      microencapsulated phase change materials.
AB  - In this article, the nonionic compound emulsifiers Tween80 and Span80 were used
      to prepare microcapsules containing phase change materials (microPCMs) with
      melamine-formaldehyde (MF) shells by in situ polymerization method. The effects
      of compound emulsifiers Tween80 and Span80 on the structure, morphologies and
      properties of microPCMs containing paraffin were studied. SEM morphological
      investigation suggests that a complex of Tween80 and Span80 as emulsifiers are
      optimal for the fabrication of microPCMs in this study compared to Tween60 or OP
      10. The diameter distributions of microPCMs synthesized with different amounts of
      compound emulsifiers are uniform, whereas compound emulsifiers' amount affect the
      mean diameter of microPCMs decreasing from 5.34 to 3.05 um. These microPCMs with
      the core/shell weight ratio 3/1 have smoother surface and a higher core content
      of 68.7% than other core/shell ratio. Anti-osmosis measurements indicate that
      microPCMs have good compactness and stable performance compared to those
      synthesized by one type of emulsifier.

PMID- 24124888
TI  - Enrichment of Bifidobacterium longum subsp. infantis ATCC 15697 within the human
      gut microbiota using alginate-poly-L-lysine-alginate microencapsulation oral
      delivery system: an in vitro analysis using a computer-controlled dynamic human
      gastrointestinal model.
AB  - This study evaluates alginate-poly-L-lysine-alginate Bifidobacterium longum
      subsp. infantis ATCC 15697-loaded microcapsules to enrich the human gut
      microbiota. The cell survival of alginate-poly-L-lysine-alginate
      microencapsulated B. infantis ATCC 15697 in gastric acid, bile, and through human
      gastrointestinal transit was investigated, as well as the formulation's effect on
      the gut microbiota. Results show that microencapsulation increases B. infantis
      ATCC 15697 cell survival at pH1.0 (33.54 +/- 2.80% versus <1.00 +/- 0.00%), pH1.5
      (41.15 +/- 2.06% versus <1.00 +/- 0.00%), pH2.0 (60.88 +/- 1.73% versus 36.01 +/-
      2.63%), pH3.0 (75.43 +/- 1.23% versus 46.30 +/- 1.43%), pH4.0 (71.40 +/- 2.02%
      versus 47.75 +/- 3.12%) and pH5.0 (73.88 +/- 3.79% versus 58.93 +/- 2.26%) (p <
      0.05). In addition, microencapsulation increases cell survival at 0.5% (76.85 +/-
      0.80% versus 70.77 +/- 0.64%), 1.0% (59.99 +/- 0.97% versus 53.47 +/- 0.58%) and
      2.0% (53.10 +/- 1.87% versus 44.59 +/- 1.52%) (p < 0.05) (w/v) bile. Finally,
      daily administration of alginate-poly-L-lysine-alginate microencapsulated B.
      infantis ATCC 15697 in a human gastrointestinal model induces a significant
      enrichment of B. infantis within the ascending (184.51 +/- 17.30% versus 53.83 +/
      17.82%; p < 0.05), transverse (174.79 +/- 25.32% versus 73.17 +/- 15.30%; p <
      0.05) and descending (94.90 +/- 25.22% versus 46.37 +/- 18.93%; p > 0.05) colonic
      microbiota.

PMID- 24124889
TI  - Transient absorption and photocurrent microscopy show that hot electron
      supercollisions describe the rate-limiting relaxation step in graphene.
AB  - Using transient absorption (TA) microscopy as a hot electron thermometer, we show
      that disorder-assisted acoustic-phonon supercollisions (SCs) best describe the
      rate-limiting relaxation step in graphene over a wide range of lattice
      temperatures (Tl = 5-300 K), Fermi energies (E(F) = +/- 0.35 eV), and optical
      probe energies (~0.3-1.1 eV). Comparison with simultaneously collected transient
      photocurrent, an independent hot electron thermometer, confirms that the rate
      limiting optical and electrical response in graphene are best described by the SC
      heat dissipation rate model, H = A(T(e)(3) - T(l)(3)). Our data further show that
      the electron cooling rate in substrate-supported graphene is twice as fast as in
      suspended graphene sheets, consistent with SC model prediction for disorder.

PMID- 24124890
TI  - Dietary quality indices vary with sociodemographic variables and anthropometric
      status among Mexican adults: a cross-sectional study. Results from the 2006
      National Health and Nutrition Survey.
AB  - OBJECTIVE: To evaluate the dietary quality of Mexican adults' diet, we
      constructed three dietary quality indices: a cardioprotective index (CPI), a
      micronutrient adequacy index (MAI) and a dietary diversity index (DDI). DESIGN:
      Data were derived from the 2006 National Health and Nutrition Survey, which is a
      national survey representative of the Mexican population with a stratified,
      multistage, probabilistic sample design. Dietary intake was assessed from an FFQ
      with 101 different foods and daily nutrient intakes were computed. The CPI
      evaluated compliance with seven WHO recommendations for the prevention of CVD,
      the MAI evaluated the intake of six micronutrients based on the estimated average
      requirements from the US Institute of Medicine and the DDI was constructed based
      on the consumption of thirty different food groups. SETTINGS: Mexico. SUBJECTS:
      Mexican adults aged 19-59 years old. RESULTS: We evaluated the diet of 15 675
      males and females. Adjusted means and adjusted proportions by age and sex were
      computed to predict adherence to dietary recommendations. Rural inhabitants,
      those living in the South and those from the lowest socio-economic status
      reported a significantly higher CPI (4.5 (se 0.08), 4.3 (se 0.08) and 4.2 (se
      0.09), respectively; P < 0.05), but a significantly lower MAI and DDI, compared
      with urban inhabitants, those from the North and those of upper socio-economic
      status (P < 0.05). CONCLUSIONS: The constructed diet quality indices identify
      nutrients and foods whose recommended intakes are not adequately consumed by the
      population. Given the epidemiological and nutritional transition that Mexico is
      experiencing, the CPI is the most relevant index and its components should be
      considered in Mexican dietary guidelines as well as in any food and nutrition
      programmes developed.

PMID- 24124894
TI  - Brunsting-Perry-type cicatricial pemphigoid with IgG autoantibodies to LAD-1.

PMID- 24124892
TI  - Ligand-accelerated ortho-C-H alkylation of arylcarboxylic acids using alkyl boron
      reagents.
AB  - A protocol for the Pd(II)-catalyzed ortho-C-H alkylation of phenylacetic and
      benzoic acids using alkylboron reagents is disclosed. Monoprotected amino acid
      ligands (MPAA) were found to significantly promote reactivity. Both potassium
      alkyltrifluoroborates and alkylboronic acids were compatible coupling partners.
      The possibility of a radical alkyl transfer to Pd(II) was also investigated. 

PMID- 24124893
TI  - "EXHALE": exercise as a strategy for rehabilitation in advanced stage lung cancer
      patients: a randomized clinical trial comparing the effects of 12 weeks
      supervised exercise intervention versus usual care for advanced stage lung cancer
      patients.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death in North America and
      Western Europe. Patients with lung cancer in general have reduced physical
      capacity, functional capacity, poor quality of life and increased levels of
      anxiety and depression. Intervention studies indicate that physical training can
      address these issues. However, there is a lack of decisive evidence regarding the
      effect of physical exercise in patients with advanced lung cancer. The aim of
      this study is to evaluate the effects of a twelve weeks, twice weekly program
      consisting of: supervised, structured training in a group of advanced lung cancer
      patients (cardiovascular and strength training, relaxation). METHODS/DESIGN: A
      randomized controlled trial will test the effects of the exercise intervention in
      216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage
      IIIb-IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary
      outcome is maximal oxygen uptake (VO2peak). Secondary outcomes are muscle
      strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient
      reported outcome (including anxiety, depression (HADS) and quality of life
      (HRQOL)). DISCUSSION: The present randomized controlled study will provide data
      on the effectiveness of a supervised exercise intervention in patients receiving
      systemic therapy for advanced lung cancer. It is hoped that the intervention can
      improve physical capacity and functional level, during rehabilitation of cancer
      patients with complex symptom burden and help them to maintain independent
      function for as long as possible. TRIAL REGISTRATION: http://ClinicalTrials.gov,
      NCT01881906.

PMID- 24124895
TI  - Nursing professionalism: a national survey of professionalism among Japanese
      nurses.
AB  - The aim of this study was to quantify the professionalism of nurses in Japan. The
      Japanese version of the Behavioural Inventory for Professionalism in Nursing was
      conducted as a national survey. Computer-generated random selection of nurses in
      Japan obtained responses from 1501 nurses. A descriptive design examined the
      levels of and differences in nursing professionalism. Comparisons of the total
      level of professionalism in educational preparation, current position, years of
      experience, and current practice setting were analysed by one-way analysis of
      variance and post hoc Tukey-Kramer multiple comparison test. The results revealed
      that Japanese nurses had low levels of professionalism, and professionalism was
      related significantly to higher educational preparation, years of experience as a
      nurse, and current position as a nursing administrator or faculty. The results
      can be used as a benchmark for continued assessments of the level of nursing
      professionalism and for further development of nursing professionalism. 

PMID- 24124891
TI  - Coupling heme and iron metabolism via ferritin H chain.
AB  - SIGNIFICANCE: Inflammation and immunity can be associated with varying degrees of
      heme release from hemoproteins, eventually leading to cellular and tissue iron
      (Fe) overload, oxidative stress, and tissue damage. Presumably, these deleterious
      effects contribute to the pathogenesis of systemic infections. RECENT ADVANCES:
      Heme release from hemoglobin sensitizes parenchyma cells to undergo programmed
      cell death in response to proinflammatory cytokines, such as tumor necrosis
      factor. This cytotoxic effect is driven by a mechanism involving intracellular
      accumulation of free radicals, which sustain the activation of the c-Jun N
      terminal kinase (JNK) signaling transduction pathway. While heme catabolism by
      heme oxygenase-1 (HO-1) prevents programmed cell death, this cytoprotective
      effect requires the co-expression of ferritin H (heart/heavy) chain (FTH), which
      controls the pro-oxidant effect of labile Fe released from the protoporphyrin IX
      ring of heme. This antioxidant effect of FTH restrains JNK activation, whereas
      JNK activation inhibits FTH expression, a cross talk that controls metabolic
      adaptation to cellular Fe overload associated with systemic infections. CRITICAL
      ISSUES AND FUTURE DIRECTIONS: Identification and characterization of the
      mechanisms via which FTH provides metabolic adaptation to tissue Fe overload
      should provide valuable information to our current understanding of the
      pathogenesis of systemic infections as well as other immune-mediated inflammatory
      diseases.

PMID- 24124896
TI  - Bilateral diffuse uveal melanocytic proliferation as a precursor to multiple
      systemic malignancies.
AB  - Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, intraocular
      paraneoplastic syndrome characterized by multiple, elevated, pigmented uveal
      lesions, diffuse thickening of the uveal tract, and rapidly progressive
      cataracts. We report a 70-year-old Caucasian male with an inferotemporal
      conjunctival-scleral pigmented lesion of the right eye. Funduscopy and
      ultrasonography revealed multiple elevated pigmented choroidal lesions in both
      eyes. Genome-wide single nucleotide polymorphism (SNP) analysis of intraoperative
      transscleral fine-needle aspiration biopsies from both eyes revealed a whole gain
      on chromosome 5. BDUMP was diagnosed, and the patient underwent a thorough
      systemic investigation, which was negative for an underlying malignancy; however,
      by maintaining a high index of suspicion, multiple malignancies were uncovered
      and appropriately treated over the ensuing years. This report presents the
      clinical, cytologic, and cytogenetic features of BDUMP, and is the first to
      demonstrate a novel finding of a whole gain in chromosome 5 by SNP analysis of
      the choroidal lesions. Additionally, this is the first case to potentially
      associate BDUMP and both transitional cell carcinoma of the bladder as well as
      renal clear cell carcinoma.

PMID- 24124897
TI  - Acoustic, perceptual and aerodynamic voice evaluation in an obese population.
AB  - OBJECTIVE: To investigate perceptual, acoustic and aerodynamic voice parameters
      in obese individuals. METHODS: Twenty obese and 20 normal-weight volunteers
      underwent voice evaluation by laryngoscopy, acoustic analysis, aerodynamic
      measurement and perceptual analysis (using the grade-roughness-breathiness
      asthenia-strain ('GRBAS') scale and the Voice Handicap Index 10 scale). Data from
      both subject groups were compared. RESULTS: No difference was found in acoustic
      analysis parameters between the two groups (p > 0.05). Maximum phonation time in
      the obese group (mean +/- standard deviation, 19.6 +/- 4.9 seconds) was
      significantly shorter than in controls (26.4 +/- 4.1 seconds) (p < 0.001),
      although the s/z ratio was very similar between the two groups. In the obese and
      control groups, the mean +/- standard deviation grade-roughness-breathiness
      asthenia-strain scores were 1 +/- 1.3 and 0.2 +/- 0.6 (p = 0.002) and the mean +/
      standard deviation Voice Handicap Index 10 scores were 0.5 +/- 1.2 and 1.2 +/-
      1.7 (p = 0.27), respectively. CONCLUSION: Obese individuals had poorer vocal
      quality as judged by the grade-roughness-breathiness-asthenia-strain scale, and
      reduced maximum phonation time. However, there was no change in voice quality as
      assessed by acoustic analysis and Vocal Handicap Index 10 score, compared with
      controls.

PMID- 24124898
TI  - Design, synthesis, and biological evaluation of 2-oxo-3,4-dihydropyrimido[4,5
      d]pyrimidinyl derivatives as new irreversible epidermal growth factor receptor
      inhibitors with improved pharmacokinetic properties.
AB  - Structural optimization of a series of 2-oxo-3,4-dihydropyrimido[4,5
      d]pyrimidinyl compounds, potential new irreversible EGFR inhibitors, was
      performed to improve pharmacokinetic properties of the compounds. This led to
      compound 2v with improved aqueous solubility and good pharmacokinetic properties
      which at the nanomolar level potently inhibits gefitinib-resistant
      EGFR(L858R/T790M) kinase and displays strong antiproliferative activity against
      H1975 nonsmall cell lung cancer cells. The new inhibitor also shows promising
      antitumor efficacy in a murine EGFR(L858R/T790M)-driven H1975 xenograft model
      without effect on body weight. These studies provide new lead compounds for
      further development of drugs for treatment of gefitinib-resistant nonsmall cell
      lung cancer patients. 

PMID- 24124899
TI  - Reductive coupling of azides mediated by an iron(II) bis(alkoxide) complex.
AB  - The iron(III) hexazene complex (RO)2Fe(MU-kappa(2):kappa(2)-AdN6Ad)Fe(OR)2 (3)
      was synthesized via reductive coupling of 1-azidoadamantane at the iron(II)
      bis(alkoxide) complex Fe(OR)2(THF)2 (2). The X-ray crystal structure depicts
      electron delocalization within the hexazene moiety. Density functional theory
      studies propose the formation of an iron azide dimer on the route to hexazene, in
      which each azide is monoreduced and the iron centers are oxidized to the 3+
      oxidation state. 

PMID- 24124900
TI  - The Pseudomonas type III effector HopQ1 activates cytokinin signaling and
      interferes with plant innate immunity.
AB  - We characterized the molecular function of the Pseudomonas syringae pv. tomato
      DC3000 (Pto) effector HopQ1. In silico studies suggest that HopQ1 might possess
      nucleoside hydrolase activity based on the presence of a characteristic aspartate
      motif. Transgenic Arabidopsis lines expressing HopQ1 or HopQ1 aspartate mutant
      variants were characterized with respect to flagellin triggered immunity,
      phenotype and changes in phytohormone content by high-performance liquid
      chromatography-MS (HPLC-MS). We found that HopQ1, but not its aspartate mutants,
      suppressed all tested immunity marker assays. Suppression of immunity was the
      result of a lack of the flagellin receptor FLS2, whose gene expression was
      abolished by HopQ1 in a promoter-dependent manner. Furthermore, HopQ1 induced
      cytokinin signaling in Arabidopsis and the elevation in cytokinin signaling
      appears to be responsible for the attenuation of FLS2 expression. We conclude
      that HopQ1 can activate cytokinin signaling and that moderate activation of
      cytokinin signaling leads to suppression of FLS2 accumulation and thus defense
      signaling. 

PMID- 24124901
TI  - Self-cleaning antireflective optical coatings.
AB  - Low-cost antireflection coatings (ARCs) on large optical surfaces are an
      ingredient-technology for high-performance solar cells. While nanoporous thin
      films that meet the zero-reflectance conditions on transparent substrates can be
      cheaply manufactured, their suitability for outdoor applications is limited by
      the lack of robustness and cleanability. Here, we present a simple method for the
      manufacture of robust self-cleaning ARCs. Our strategy relies on the self
      assembly of a block-copolymer in combination with silica-based sol-gel chemistry
      and preformed TiO2 nanocrystals. The spontaneous dense packing of copolymer
      micelles followed by a condensation reaction results in an inverse opal-type
      silica morphology that is loaded with TiO2 photocatalytic hot-spots. The very low
      volume fraction of the inorganic network allows the optimization of the
      antireflecting properties of the porous ARC despite the high refractive index of
      the embedded photocatalytic TiO2 nanocrystals. The resulting ARCs combine high
      optical and self-cleaning performance and can be deposited onto flexible plastic
      substrates. 

PMID- 24124902
TI  - AR3 messenger ribonucleic acid expression and its functional implication in human
      primary testicular failure.
AB  - AR3, a major one of androgen receptor (AR) splice variants, has been shown to
      play a pivotal role in concert with AR signalling in prostate cancer. The present
      study was undertaken to characterise the expression pattern of AR3 in normal and
      impaired spermatogenesis. Expression of AR3 mRNA showed significantly lower level
      in testicular tissues with impaired spermatogenesis when compared to normal
      tissues. This aberrant expression profile of AR3 in human pathological testes was
      further confirmed by immunoblotting analysis. Moreover, in situ hybridisation
      studies revealed that the transcripts of the gene were dominantly localised in
      the pachytene spermatocytes and round spermatids, suggesting a potential
      involvement of this transcriptional regulator in the auto-/paracrine regulation
      of meiotic and post-meiotic differentiation. This hypothesis was strengthened by
      the observation that AR3 mRNA expression was positively correlated to average
      seminiferous tubule score and was negatively correlated to serum FSH level. To
      the best of our knowledge, such a distinct expression profile of AR3 has not been
      reported previously in human testis. Overall, our data are suggestive of a novel
      site of action of AR3 during human spermatogenesis and should shed light on the
      complicated circuit composed of AR and its splice variants. 

PMID- 24124903
TI  - Tracing the origin of paralytic shellfish toxins in scallop Patinopecten
      yessoensis in the northern Yellow Sea.
AB  - Some dinoflagellate species within the genera Alexandrium, Gymnodinium and
      Pyrodinium are well-known producers of paralytic shellfish toxins (PST), which
      led to many poisoning incidents around the world. In the northern Yellow Sea, an
      important mariculture zone for scallop Patinopecten yessoensis, PST have been
      frequently detected from scallops. However, there is little knowledge concerning
      PST-producing microalgae in this region so far. In cruises carried out in 2011
      and 2012, scallop and phytoplankton samples were collected from the northern
      Yellow Sea. PST were detected from scallops by high-performance liquid
      chromatography with fluorescence detection (HPLC-FLD). Toxin content and profile
      were remarkably different among the four tissues, i.e. viscera, adductor muscle,
      mantle and gonad, suggesting apparent toxin transfer and transformation in
      scallops. Viscera always had the highest content of PST dominated by low-potency
      N-sulfocarbamoyl toxins C1 and C2, which closely resembled the toxin profiles of
      net-concentrated phytoplankton samples in spring. Based on the morphological
      features, cells of Alexandrium spp. in net-concentrated phytoplankton samples
      were picked out and a partial sequence of the large subunit ribosomal RNA gene
      (LSU rDNA) was amplified using a single-cell polymerase chain reaction (PCR)
      method. Cells of both toxic A. tamarense species complex and non-toxic A. affine
      were identified from the phytoplankton samples based on the partial LSU rDNA
      sequence information. According to these findings, it is implied that A.
      tamarense species complex is the major toxic species related to PST contamination
      in scallops of the northern Yellow Sea. The presence of both toxic and non-toxic
      Alexandrium spp. in this region requires for a species-specific method to monitor
      the distribution and dynamics of A. tamarense species complex. 

PMID- 24124905
TI  - Damage to skin extracellular matrix induced by UV exposure.
AB  - SIGNIFICANCE: Chronic exposure to environmental ultraviolet radiation (UVR) plays
      a key role in both photocarcinogenesis and induction of accelerated skin aging.
      Although the spatiotemporal consequences of UVR exposure for the composition and
      architecture of the dermal extracellular matrix (ECM) are well characterized, the
      pathogenesis of photoaging remains poorly defined. Given the compelling evidence
      for the role of reactive oxygen species (ROS) as mediators of photoaging, UVR
      exposed human skin may be an accessible model system in which to characterize the
      role of oxidative damage in both internal and external tissues. RECENT ADVANCES:
      Although the cell-mediated degradation of dermal components via UVR-induced
      expression of ECM proteases has long been identified as an integral part of the
      photoaging pathway, the relative importance and identity of cellular and
      extracellular photosensitizers (direct hit and bystanders models, respectively)
      in initiating this enzymatic activity is unclear. Recently, both age-related
      protein glycation and relative amino-acid composition have been identified as
      potential risk factors for photo-ionization and/or photo-sensitization. Here, we
      propose a selective multi-hit model of photoaging. CRITICAL ISSUES: Bioinformatic
      analyses can be employed to identify candidate UVR targets/photosensitizers, but
      the action of UVR on protein structure and/or ROS production should be verified
      experimentally. Crucially, in the case of biochemically active ECM components
      such as fibronectin and fibrillin, the downstream effects of photo-degradation on
      tissue homeostasis remain to be confirmed. FUTURE DIRECTIONS: Both topical
      antioxidants and inhibitors of detrimental cell signaling may be effective in
      abrogating the effects of specific UVR-mediated protein degradation in the
      dermis.

PMID- 24124904
TI  - Proteomic evidence for genetic epistasis: ClpR4 mutations switch leaf variegation
      to virescence in Arabidopsis.
AB  - Chloroplast development in plants is regulated by a series of coordinated
      biological processes. In this work, a genetic suppressor screen for the leaf
      variegation phenotype of the thylakoid formation 1 (thf1) mutant combined with a
      proteomic assay was employed to elucidate this complicated network. We identified
      a mutation in ClpR4, named clpR4-3, which leads to leaf virescence and also
      rescues the var2 variegation. Proteomic analysis showed that the chloroplast
      proteome of clpR4-3 thf1 is dominantly controlled by clpR4-3, providing molecular
      mechanisms that cause genetic epistasis of clpR4-3 to thf1. Classification of the
      proteins significantly mis-regulated in the mutants revealed that those
      functioning in the expression of plastid genes are oppositely regulated while
      proteins functioning in antioxidative stress, protein folding, and starch
      metabolism are changed in the same direction between thf1 and clpR4-3. The levels
      of FtsHs including FtsH2/VAR2, FtsH8, and FtsH5/VAR1 are greatly reduced in thf1
      compared with those in the wild type, but are higher in clpR4-3 thf1 than in
      thf1. Quantitative PCR analysis revealed that FtsH expression in clpR4-3 thf1 is
      regulated post-transcriptionally. In addition, a number of ribosomal proteins are
      less expressed in the clpR4-3 proteome, which is in line with the reduced levels
      of rRNAs in clpR4-3. Furthermore, knocking out PRPL11, one of the most
      downregulated proteins in the clpR4-3 thf1 proteome, rescues the leaf variegation
      phenotype of the thf1 and var2 mutants. These results provide insights into
      molecular mechanisms by which the virescent clpR4-3 mutation suppresses leaf
      variegation of thf1 and var2.

PMID- 24124907
TI  - Temporality in British young women's magazines: food, cooking and weight loss.
AB  - OBJECTIVE: The present study examines seasonal and temporal patterns in food
      related content of two UK magazines for young women focusing on food types,
      cooking and weight loss. DESIGN: Content analysis of magazines from three time
      blocks between 1999 and 2011. SETTING: Desk-based study. SUBJECTS: Ninety-seven
      magazines yielding 590 advertisements and 148 articles. RESULTS: Cluster analysis
      of type of food advertising produced three clusters of magazines, which reflected
      recognised food behaviours of young women: vegetarianism, convenience eating and
      weight control. The first cluster of magazines was associated with Christmas and
      Millennium time periods, with advertising of alcohol, coffee, cheese, vegetarian
      meat substitutes and weight-loss pills. Recipes were prominent in article content
      and tended to be for cakes/desserts, luxury meals and party food. The second
      cluster was associated with summer months and 2010 issues. There was little
      advertising for conventional foods in cluster 2, but strong representation of
      diet plans and foods for weight loss. Weight-loss messages in articles focused on
      short-term aesthetic goals, emphasising speedy weight loss without giving up nice
      foods or exercising. Cluster 3 magazines were associated with post-New Year and
      2005 periods. Food advertising was for everyday foods and convenience products,
      with fewer weight-loss products than other clusters; conversely, article content
      had a greater prevalence of weight-loss messages. CONCLUSIONS: The cyclical
      nature of magazine content - indulgence and excess encouraged at Christmas,
      restraint recommended post-New Year and severe dieting advocated in the summer
      months - endorses yo-yo dieting behaviour and may not be conducive to public
      health.

PMID- 24124906
TI  - Dichotomous hydrogen atom transfer vs proton-coupled electron transfer during
      activation of X-H bonds (X = C, N, O) by nonheme iron-oxo complexes of variable
      basicity.
AB  - We describe herein the hydrogen-atom transfer (HAT)/proton-coupled electron
      transfer (PCET) reactivity for Fe(IV)-oxo and Fe(III)-oxo complexes (1-4) that
      activate C-H, N-H, and O-H bonds in 9,10-dihydroanthracene (S1),
      dimethylformamide (S2), 1,2-diphenylhydrazine (S3), p-methoxyphenol (S4), and 1,4
      cyclohexadiene (S5). In 1-3, the iron is pentacoordinated by tris[N'-tert
      butylureaylato)-N-ethylene]aminato ([H3buea](3-)) or its derivatives. These
      complexes are basic, in the order 3 ? 1 > 2. Oxidant 4, [Fe(IV)N4Py(O)](2+)
      (N4Py: N,N-bis(2-pyridylmethyl)bis(2-pyridyl)methylamine), is the least basic
      oxidant. The DFT results match experimental trends and exhibit a mechanistic
      spectrum ranging from concerted HAT and PCET reactions to concerted-asynchronous
      proton transfer (PT)/electron transfer (ET) mechanisms, all the way to PT. The
      singly occupied orbital along the O...H...X (X = C, N, O) moiety in the TS shows
      clearly that in the PCET cases, the electron is transferred separately from the
      proton. The Bell-Evans-Polanyi principle does not account for the observed
      reactivity pattern, as evidenced by the scatter in the plot of calculated barrier
      vs reactions driving forces. However, a plot of the deformation energy in the TS
      vs the respective barrier provides a clear signature of the HAT/PCET dichotomy.
      Thus, in all C-H bond activations, the barrier derives from the deformation
      energy required to create the TS, whereas in N-H/O-H bond activations, the
      deformation energy is much larger than the corresponding barrier, indicating the
      presence of a stabilizing interaction between the TS fragments. A valence bond
      model is used to link the observed results with the basicity/acidity of the
      reactants. 

PMID- 24124910
TI  - Raman spectrum of pyrope garnet. A quantum mechanical simulation of frequencies,
      intensities, and isotope shifts.
AB  - The Raman spectrum of pyrope garnet is simulated in ab initio quantum mechanical
      calculations, using an all-electron Gaussian-type basis set and the hybrid B3LYP
      functional. Frequencies calculated for the 25 Raman-active modes are in excellent
      agreement with the several sets of experimental data, with the mean absolute
      difference ranging from 4 to 8 cm(-1). Comparison of the computed and
      experimental spectrum shows excellent agreement for most of the intensities as
      well. Modes missing from experiment are shown to be characterized by low
      (computed) intensity. Spurious peaks in the experimental spectra are also
      identified. The isotopic effect has been simulated for (24)Mg -> (26)Mg
      substitution and shows excellent agreement with shifts reported in one of the
      experiments. Agreement is excellent for all but one mode, which turns out to be
      attributed to the wrong symmetry in the experiment. 

PMID- 24124909
TI  - Inflammation induces neuro-lymphatic protein expression in multiple sclerosis
      brain neurovasculature.
AB  - BACKGROUND: Multiple sclerosis (MS) is associated with ectopic lymphoid follicle
      formation. Podoplanin+ (lymphatic marker) T helper17 (Th17) cells and B cell
      aggregates have been implicated in the formation of tertiary lymphoid organs
      (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin
      expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium,
      we investigated whether the pathophysiology of MS involves inductions of
      lymphatic proteins in the inflamed neurovasculature. METHODS: We assessed the
      protein levels of lymphatic vessel endothelial hyaluronan receptor and
      podoplanin, which are specific to the lymphatic system and prospero-homeobox
      protein-1, angiopoietin-2, vascular endothelial growth factor-D, vascular
      endothelial growth factor receptor-3, which are expressed by both lymphatic
      endothelium and neurons. Levels of these proteins were measured in postmortem
      brains and sera from MS patients, in the myelin proteolipid protein (PLP)-induced
      EAE and Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating
      disease (TMEV-IDD) mouse models and in cell culture models of inflamed
      neurovasculature. RESULTS AND CONCLUSIONS: Intense staining for LYVE-1 was found
      in neurons of a subset of MS patients using immunohistochemical approaches. The
      lymphatic protein, podoplanin, was highly expressed in perivascular inflammatory
      lesions indicating signaling cross-talks between inflamed brain vasculature and
      lymphatic proteins in MS. The profiles of these proteins in MS patient sera
      discriminated between relapsing remitting MS from secondary progressive MS and
      normal patients. The in vivo findings were confirmed in the in vitro cell culture
      models of neuroinflammation.

PMID- 24124911
TI  - Impact of in vivo reflectance confocal microscopy on the number needed to treat
      melanoma in doubtful lesions.
AB  - BACKGROUND: The number needed to treat (NNT) ratio is an effective method for
      measuring accuracy in melanoma detection. Dermoscopy reduces the number of false
      positives and subsequently unnecessary excisions. In vivo reflectance confocal
      microscopy (RCM) is a noninvasive technique that allows examination of the skin
      with cellular resolution. OBJECTIVES: To assess the impact of RCM analysis on the
      number of equivocal lesions, assumed to be melanocytic, excised for every
      melanoma. METHODS: Consecutive patients (n = 343) presenting with doubtful
      lesions were considered for enrolment. The lesions were analysed by dermoscopy
      and RCM, with histopathological assessment considered the reference standard. The
      main outcome was the NNT, calculated as the proportion of equivocal lesions
      excised for every melanoma. RESULTS: Dermoscopy alone obtained a hypothetical NNT
      of 3.73; the combination of dermoscopy and RCM identified 264 equivocal lesions
      that qualified for excision, 92 of which were confirmed to be a melanoma,
      resulting in an NNT of 2.87, whereas the analysis of RCM images classified 103
      lesions as melanoma, with a consequent NNT of 1.12. The difference in the
      reduction of this ratio was statistically significant between the three groups (P
      < 0.0001). There was no significant improvement in sensitivity when comparing the
      combination of dermoscopy and RCM with RCM alone (94.6% vs. 97.8%; P = 0.043).
      However, the differences between specificities were statistically significant (P
      < 1 * 10(-6) ), favouring RCM alone. CONCLUSION: The addition of RCM analysis to
      dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and
      could be a means for reducing the economic impact associated with the management
      of skin cancer.

PMID- 24124912
TI  - Quality of life, depression, adherence to treatment and illness perception of
      patients on haemodialysis.
AB  - The purpose of this study was to explore the relationship between quality of
      life, depression, perception of seriousness of illness and adherence to treatment
      among Jordanian patients with end stage renal disease on maintenance
      haemodialysis. The study was carried out using a descriptive, correlation design.
      A convenience sample of 244 participants was recruited from four major dialysis
      units in Amman. A self-report questionnaire included demographic data, adherence
      to treatment and perception of seriousness of illness. Quality of Life Index and
      Beck Depression Inventory were used for data collection. There was a negative
      correlation between quality of life and depression (r = -0.05, P = 0.000).
      Depression was higher among women than men, whereas both gender had low quality
      of life scores. Higher quality of life has been associated with perceived
      seriousness of illness and more adherence to treatment regimen. This study
      provides preliminary evidence to develop culturally sensitive nursing strategies
      to asses and manage depression, enhance quality of life and adherence to
      treatment of patients on haemodialysis. 

PMID- 24124913
TI  - Refractory rheumatoid factor positive polyarthritis in a female adolescent
      already suffering from type 1 diabetes mellitus and Hashimoto's thyroiditis
      successfully treated with etanercept.
AB  - Type 1 diabetes mellitus may be associated with many autoimmune diseases with the
      common autoimmune pathogenesis. We describe the case of a girl suffering from
      Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the
      childhood and, due to the onset of Juvenile Idiopathic Arthritis during
      adolescence, for three years practiced therapy with an anti-TNF drug, etanercept
      . Currently her inflammatory markers are normal, arthritis is inactive and
      diabetes is well controlled. During the treatment with anti-TNF drug we observed
      a significative reduction of insulin dose, probably due to an increased tissue
      sensitivity secondary to the suppression of the activity of TNF-alpha. Several
      clinical trials that have evaluated the effect of immunomodulatory agents in
      diabetic patients, especially in those with recent onset of disease, were already
      performed but further studies of longer duration on a larger population are
      needed to assess the role of biologic drugs and immunotherapy in this group of
      patients. 

PMID- 24124915
TI  - Nursing Grand Rounds: The North Queensland, Australia, Experience.

PMID- 24124914
TI  - Role of neck dissection for metastatic nonseminomatous testicular carcinoma: case
      report and literature review.
AB  - OBJECTIVES: To review the incidence, treatment and prognosis of testicular
      carcinoma metastatic to the neck, and to propose a selective neck dissection be
      performed for residual disease post-chemotherapy. CASE REPORT: A 17-year-old
      young man with metastatic testicular carcinoma presented with a left neck mass. A
      palpable neck mass is the initial sign in approximately 5 per cent of cases of
      metastatic testicular teratoma. Approximately 30 per cent of patients with
      advanced-stage testicular cancer have extra-retroperitoneal disease post
      chemotherapy, which requires resection. The presented patient underwent a left
      selective neck dissection, thymectomy, median sternotomy, left thoracotomy and
      mediastinal lymph node dissection. Eighteen months later, a computed tomography
      scan of the thorax showed no evidence of disease recurrence in the neck or
      mediastinum. CONCLUSION: While surgical management of testicular cancer
      retroperitoneal metastases is well described, there is limited literature on the
      management of cervical lymph node metastases. In the presented case of metastatic
      testicular carcinoma with cervical lymph node metastases, a selective neck
      dissection was successfully performed for a post-chemotherapy mass.

PMID- 24124916
TI  - Biomolecular recognition principles for bionanocombinatorics: an integrated
      approach to elucidate enthalpic and entropic factors.
AB  - Bionanocombinatorics is an emerging field that aims to use combinations of
      positionally encoded biomolecules and nanostructures to create materials and
      devices with unique properties or functions. The full potential of this new
      paradigm could be accessed by exploiting specific noncovalent interactions
      between diverse palettes of biomolecules and inorganic nanostructures.
      Advancement of this paradigm requires peptide sequences with desired binding
      characteristics that can be rationally designed, based upon fundamental,
      molecular-level understanding of biomolecule-inorganic nanoparticle interactions.
      Here, we introduce an integrated method for building this understanding using
      experimental measurements and advanced molecular simulation of the binding of
      peptide sequences to gold surfaces. From this integrated approach, the importance
      of entropically driven binding is quantitatively demonstrated, and the first
      design rules for creating both enthalpically and entropically driven nanomaterial
      binding peptide sequences are developed. The approach presented here for gold is
      now being expanded in our laboratories to a range of inorganic nanomaterials and
      represents a key step toward establishing a bionanocombinatorics assembly
      paradigm based on noncovalent peptide-materials recognition. 

PMID- 24124918
TI  - Continuing Education Needs of Nurses in a Voluntary Continuing Nursing Education
      State.

PMID- 24124917
TI  - Decreased miR-106a inhibits glioma cell glucose uptake and proliferation by
      targeting SLC2A3 in GBM.
AB  - BACKGROUND: MiR-106a is frequently down-regulated in various types of human
      cancer. However the underlying mechanism of miR-106a involved in glioma remains
      elusive. METHODS: The association of miR-106a with glioma grade and patient
      survival was analyzed. The biological function and target of miR-106a were
      determined by bioinformatic analysis and cell experiments (Western blot,
      luciferase reporter, cell cycle, ntracellular ATP production and glucose uptake
      assay). Finally, rescue expression of its target SLC2A3 was used to test the role
      of SLC2A3 in miR-106a-mediated cell glycolysis and proliferation. RESULTS: Here
      we showed that miR-106a was a tumor suppressor miRNA was involved in GBM cell
      glucose uptake and proliferation. Decreased miR-106a in GBM tissues and conferred
      a poor survival of GBM patients. SLC2A3 was identified as a core target of miR
      106a in GBM cells. Inhibition of SLC2A3 by miR-106a attenuated cell proliferation
      and inhibited glucose uptake. In addition, for each biological process we
      identified ontology-associated transcripts that significantly correlated with
      SLC2A3 expression. Finally, the expression of SLC2A3 largely abrogated miR-106a
      mediated cell proliferation and glucose uptake in GBM cells. CONCLUSIONS: Taken
      together, miR-106a and SLC2A3 could be potential therapeutic approaches for GBM.

PMID- 24124919
TI  - 6-(1-Benzyl-1H-pyrrol-2-yl)-2,4-dioxo-5-hexenoic acids as dual inhibitors of
      recombinant HIV-1 integrase and ribonuclease H, synthesized by a parallel
      synthesis approach.
AB  - The increasing efficiency of HAART has helped to transform HIV/AIDS into a
      chronic disease. Still, resistance and drug-drug interactions warrant the
      development of new anti-HIV agents. We previously discovered hit 6, active
      against HIV-1 replication and targeting RNase H in vitro. Because of its diketo
      acid moiety, we speculated that this chemotype could serve to develop dual
      inhibitors of both RNase H and integrase. Here, we describe a new series of 1
      benzyl-pyrrolyl diketohexenoic derivatives, 7a-y and 8a-y, synthesized following
      a parallel solution-phase approach. Those 50 analogues have been tested on
      recombinant enzymes (RNase H and integrase) and in cell-based assays.
      Approximately half (22) exibited inhibition of HIV replication. Compounds 7b, 7u,
      and 8g were the most active against the RNase H activity of reverse
      transcriptase, with IC50 values of 3, 3, and 2.5 MUM, respectively. Compound 8g
      was also the most potent integrase inhibitor with an IC50 value of 26 nM. 

PMID- 24124920
TI  - Measure of surface potential at the aqueous-oxide nanoparticle interface by XPS
      from a liquid microjet.
AB  - We show that the surface potential at a water-oxide nanoparticle (NP) interface,
      long considered an immeasurable direct quantity, can be measured by X-ray
      photoelectron spectroscopy (XPS) from a liquid microjet. This new method does not
      require a priori knowledge of the particles' surface structure or of the ion
      distribution throughout the electrical double layer for its interpretation and
      can be applied to any colloidal suspension independent of composition, particle
      size and shape, and solvent. We demonstrate the application for aqueous
      suspensions of 9 nm colloidal silica (SiO2) at pH 0.3 and 10.0, where the surface
      potential changes from positive to negative. The experimental results are
      compared with calculated surface potentials based on Guoy-Chapman theory and are
      shown to be in good agreement. 

PMID- 24124921
TI  - Combination of intralesional verapamil and oral antioxidants for Peyronie's
      disease: a prospective, randomised controlled study.
AB  - The aim of this study was to evaluate the efficacy of the association of
      intralesional verapamil (ILV) injection with oral antioxidants compared with ILV
      monotherapy in patients with early onset of Peyronie's disease (PD) at 12-week
      follow-up. Group A (n = 52) received ILV 10 mg weekly for 12 weeks, while group B
      (n = 53) received ILV 10 mg weekly for 12 weeks + antioxidants orally one tablet
      once a day for 3 months. The main efficacy outcomes were the change in plaque
      size (PS), penile curvature (PC), visual analogue score (VAS), IIEF-15 and IIEF
      15 subdomains. Both groups showed significant improvement from baseline to week
      12 relative to PS and PC, while group B also in IIEF-15 score (mean difference:
      5.51, P < 0.01) and VAS (mean difference: -2.71, P < 0.01). No significant
      differences were observed between both groups in PS and PC. Finally, both groups
      showed significant increase in orgasmic function (IIEF-OF) and overall
      satisfaction (IIEF-OS), while group B showed significant improvement also in
      intercourse satisfaction (IIEF-IS). Significant differences were found relative
      to IIEF-OF, IIEF-IS, IIEF-OS and VAS scores in the group B compared with group A.
      Patients affected by PD may benefit from combination treatment with ILV and oral
      antioxidants thanks to the improvement in IIEF-OF, IIEF-IS and IIEF-OS at 12
      weeks.

PMID- 24124922
TI  - Stomatal optimisation in relation to atmospheric CO2.

PMID- 24124923
TI  - Reversible chemisorption of sulfur dioxide in a spin crossover porous
      coordination polymer.
AB  - The chemisorption of sulfur dioxide (SO2) on the Hofmann-like spin crossover
      porous coordination polymer (SCO-PCP) {Fe(pz)[Pt(CN)4]} has been investigated at
      room temperature. Thermal analysis and adsorption-desorption isotherms showed
      that ca. 1 mol of SO2 per mol of {Fe(pz)[Pt(CN)4]} was retained in the pores.
      Nevertheless, the SO2 was loosely attached to the walls of the host network and
      completely released in 24 h at 298 K. Single crystals of {Fe(pz)[Pt(CN)4]}.nSO2
      (n ~ 0.25) were grown in water solutions saturated with SO2, and its crystal
      structure was analyzed at 120 K. The SO2 molecule is coordinated to the Pt(II)
      ion through the sulfur atom ion, Pt-S = 2.585(4) A. This coordination slightly
      stabilizes the low-spin state of the Fe(II) ions shifting the critical
      temperatures of the spin transition by 8-12 K. DFT calculations have been
      performed to rationalize these observations. 

PMID- 24124924
TI  - Association between expression of X-linked inhibitor of apoptosis protein and the
      clinical outcome in a BRAF V600E-prevalent papillary thyroid cancer population.
AB  - BACKGROUND: The X-linked inhibitor of apoptosis protein (XIAP) is associated with
      carcinogenesis, cancer progression, and metastasis through inhibition of the
      caspase-mediated apoptotic pathway. The BRAF(V600E) mutation is the most common
      genetic alteration and an established prognostic marker in papillary thyroid
      cancer (PTC). The prevalence of the BRAF mutation is very high and is up to 80%
      in Korean PTC patients. In the present study, we evaluated the potential role of
      XIAP expression as a novel prognostic marker to predict recurrence, in
      combination with the BRAF(V600E) mutational status. METHODS: The study enrolled
      164 patients with conventional PTC who underwent bilateral thyroidectomy followed
      by immediate (131)I ablation. The presence of the BRAF(V600E) mutation was
      evaluated by direct sequencing. The degree of XIAP expression was evaluated by
      immunohistochemical (IHC) staining using a monoclonal antibody. RESULTS: The
      BRAF(V600E) mutation was found in 123 of 164 patients (75%) with classical PTC.
      XIAP expression was positive in 128 of 164 patients (75%), and positive XIAP
      expression was significantly associated with the presence of lateral cervical
      lymph node metastases (p=0.01). XIAP expression was more frequent in BRAF(V600E)
      mutated PTCs than in BRAF wild type PTCs (p=0.048). The BRAF(V600E) mutation was
      significantly associated with cancer recurrence in study subjects (hazard
      ratio=2.98, p=0.039). PTCs positive for the BRAF(V600E) mutation but negative for
      XIAP expression had a significantly higher rate of recurrent PTC (hazard
      ratio=4.53, p=0.012). CONCLUSION: The evaluation of XIAP expression and BRAF
      mutational analysis was more useful for the prediction of cancer recurrence in
      patients with PTC than BRAF genotype alone.

PMID- 24124925
TI  - Rye Pm8 and wheat Pm3 are orthologous genes and show evolutionary conservation of
      resistance function against powdery mildew.
AB  - The improvement of wheat through breeding has relied strongly on the use of
      genetic material from related wild and domesticated grass species. The 1RS
      chromosome arm from rye was introgressed into wheat and crossed into many wheat
      lines, as it improves yield and fungal disease resistance. Pm8 is a powdery
      mildew resistance gene on 1RS which, after widespread agricultural cultivation,
      is now widely overcome by adapted mildew races. Here we show by homology-based
      cloning and subsequent physical and genetic mapping that Pm8 is the rye
      orthologue of the Pm3 allelic series of mildew resistance genes in wheat. The
      cloned gene was functionally validated as Pm8 by transient, single-cell
      expression analysis and stable transformation. Sequence analysis revealed a
      complex mosaic of ancient haplotypes among Pm3- and Pm8-like genes from different
      members of the Triticeae. These results show that the two genes have evolved
      independently after the divergence of the species 7.5 million years ago and kept
      their function in mildew resistance. During this long time span the co-evolving
      pathogens have not overcome these genes, which is in strong contrast to the
      breakdown of Pm8 resistance since its introduction into commercial wheat 70 years
      ago. Sequence comparison revealed that evolutionary pressure acted on the same
      subdomains and sequence features of the two orthologous genes. This suggests that
      they recognize directly or indirectly the same pathogen effectors that have been
      conserved in the powdery mildews of wheat and rye.

PMID- 24124926
TI  - Review of the registration of clinical trials in UMIN-CTR from 2 June 2005 to 1
      June 2010 - focus on Japan domestic, academic clinical trials.
AB  - BACKGROUND: Established on 1 June 2005, the University Hospital Medical
      Information Network Clinical Trials Registry (UMIN-CTR) is the largest clinical
      trial registry in Japan, and joined the World Health Organization (WHO) registry
      network in October 2008. Our aim was to understand the registration trend and
      overall characteristics of Japan domestic, academic (non-industry-funded)
      clinical trials, which constitute the main body of registrations in UMIN-CTR. In
      addition, we aimed to investigate the accessibility of clinical trials in UMIN
      CTR to people worldwide, as well as the accessibility of clinical trials
      conducted in Japan but registered abroad to Japanese people in the Japanese
      language. METHODS: We obtained the data for registrations in UMIN-CTR from the
      UMIN Center, and extracted Japan domestic, academic clinical trials to analyze
      their registration trend and overall characteristics. We also investigated how
      many of the trials registered in UMIN-CTR could be accessed from the
      International Clinical Trials Registry Platform (ICTRP). Finally, we searched
      ClinicalTrials.gov for all clinical trials conducted in Japan and investigated
      how many of them were also registered in Japanese registries. All of the above
      analyses included clinical trials registered from 2 June 2005 to 1 June 2010.
      RESULTS: During the period examined, the registration trend showed an obvious
      peak around September 2005 and rapid growth from April 2009. Of the registered
      trials, 46.4% adopted a single-arm design, 34.5% used an active control, only
      10.9% were disclosed before trial commencement, and 90.0% did not publish any
      results. Overall, 3,063 of 3,064 clinical trials registered in UMIN-CTR could be
      accessed from ICTRP. Only 8.7% of all clinical trials conducted in Japan and
      registered in ClinicalTrials.gov were also registered in Japanese registries.
      CONCLUSIONS: The International Committee of Medical Journal Editors (ICMJE)
      announcements about clinical trial registration and the Ethical Guidelines for
      Clinical Research published by the Japanese government are considered to have
      promoted clinical trial registration in UMIN-CTR. However, problems associated
      with trial design, retrospective registration, and publication of trial results
      need to be addressed in future. Almost all clinical trials registered in UMIN-CTR
      are accessible to people worldwide through ICTRP. However, many trials conducted
      in Japan but registered abroad cannot be accessed from Japanese registries in
      Japanese.

PMID- 24124927
TI  - Exploration of protein-protein interaction effects on alpha-2-macroglobulin in an
      inhibition of serine protease through gene expression and molecular simulations
      studies.
AB  - In Prophenoloxidase (ProPO) cascade, two targets namely serine protease and alpha
      2-macroglobulin are key regulators involved in the defense system of crustaceans.
      In biological systems, routine role of cell systems requires the understanding in
      protein-protein interactions through experimental and theoretical concepts, which
      might yield useful insights into the cellular responses. Response of cells to
      regulating the immune system is governed by the interactions-involved
      biomolecular simulations. Unfortunately, studies on the inhibitors (SP and alpha
      2M) that negatively regulate the proPO system or melanization in penaeid shrimp
      are not yet available. In order to understand how these interactions change the
      proPO mechanism in Indian white shrimp Fenneropenaeus indicus was determined. In
      F. indicus, innate immune system is in a sensitive balance of intricate
      interactions; elucidating these interactions by the integration of in silico and
      in vitro has great potential. We have determined the expression of both the SP
      and alpha-2M enzymes in regulatory mechanism, which are analyzed through qRT-PCR,
      protein-protein docking, and simulation studies. From this work, we propose a
      novel approach for studying an organism at the systems level by integrating
      genome-wide computational analysis and the gene expression data. 

PMID- 24124928
TI  - Therapy-resistant folliculitis decalvans and lichen planopilaris successfully
      treated with adalimumab.

PMID- 24124929
TI  - Disruption of functional networks in dyslexia: a whole-brain, data-driven
      analysis of connectivity.
AB  - BACKGROUND: Functional connectivity analyses of functional magnetic resonance
      imaging data are a powerful tool for characterizing brain networks and how they
      are disrupted in neural disorders. However, many such analyses examine only one
      or a small number of a priori seed regions. Studies that consider the whole brain
      frequently rely on anatomic atlases to define network nodes, which might result
      in mixing distinct activation time-courses within a single node. Here, we improve
      upon previous methods by using a data-driven brain parcellation to compare
      connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the
      first whole-brain functional connectivity analysis of dyslexia. METHODS: Whole
      brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n
      = 104; 64 NI, 40 DYS) readers. RESULTS: Compared to NI readers, DYS readers
      showed divergent connectivity within the visual pathway and between visual
      association areas and prefrontal attention areas; increased right-hemisphere
      connectivity; reduced connectivity in the visual word-form area (part of the left
      fusiform gyrus specialized for printed words); and persistent connectivity to
      anterior language regions around the inferior frontal gyrus. CONCLUSIONS:
      Together, findings suggest that NI readers are better able to integrate visual
      information and modulate their attention to visual stimuli, allowing them to
      recognize words on the basis of their visual properties, whereas DYS readers
      recruit altered reading circuits and rely on laborious phonology-based "sounding
      out" strategies into adulthood. These results deepen our understanding of the
      neural basis of dyslexia and highlight the importance of synchrony between
      diverse brain regions for successful reading.

PMID- 24124930
TI  - Nutritional and eating education improves knowledge and practice of patients with
      type 2 diabetes concerning dietary intake and blood glucose control in an
      outlying city of China.
AB  - OBJECTIVE: To describe the knowledge, attitudes and practices of type 2 diabetics
      in Yakeshi City and to assess the effect of implementation of nutritional and
      eating education in enhancing knowledge and practices regarding a healthy diet.
      DESIGN: A questionnaire-based survey was conducted with 162 diabetics to
      determine their nutrition knowledge, attitudes and practices; fifty-four
      participants received nutritional and eating education for 6 months. Diabetes
      related nutrition knowledge, awareness, practice accuracy, dietary intake and
      glycaemic control were assessed before and after education. SETTING: Yakeshi, a
      remote city in northern China. SUBJECTS: A total of 162 type 2 diabetics
      recruited from three hospitals, fifty-four of whom were selected randomly to
      receive education. RESULTS: Among the 162 respondents, most diabetics (75%)
      considered that controlling diet was important in the methods of controlling
      blood glucose. Scores for knowledge, practices and overall KAP (knowledge
      attitude-practice) were low, but scores for attitude were high. Participants with
      diabetes education experiences, practice duration over 1 year or high education
      level all had higher scores for KAP (P < 0.001, P < 0.05 and P < 0.001,
      respectively) than their counterparts. After education, patients' nutrition
      knowledge, awareness and practice accuracy improved significantly (P < 0.05). The
      rates of patients with recommended daily intake of vegetables, grains and dairy
      were boosted (P < 0.05). Various nutrient intakes increased (P < 0.05) but not
      protein, Fe, Zn and Se. Significant improvements were also found in glycaemic
      control (P < 0.05). CONCLUSIONS: Diabetics in Yakeshi had positive attitudes, but
      relatively poor nutrition knowledge and practices. Nutritional and eating
      education was effective in improving diabetics' nutrition knowledge and
      practices, and this optimal practice helped them control blood glucose
      effectively.

PMID- 24124931
TI  - Selective photoinduced ligand exchange in a new tris-heteroleptic Ru(II) complex.
AB  - The complex cis-[Ru(biq)(phen)(CH3CN)2](2+) (1, biq = 2,2'-biquinoline, phen =
      1,10-phenathroline) displays selective photosubstitution of only one CH3CN ligand
      with a solvent molecule upon irradiation with low energy light (lambda(irr) >=
      550 nm), whereas both ligands exchange with lambda(irr) >= 420 nm. In contrast,
      [Ru(phen)2(CH3CN)2](2+) (2) and [Ru(biq)2(CH3CN)2](2+) (3) exchange both CH3CN
      ligands with similar rates upon irradiation with a broad range of wavelengths.
      The photolysis of 1 in the presence of pyridine (py) results in the formation of
      the intermediate cis-[Ru(biq)(phen)(py)(MeCN)](2+), which was isolated and
      characterized by X-ray crystallography, revealing that the CH3CN positioned trans
      to the phen ligand is more photolabile than that positioned trans to the biq
      ligand when irradiated with low energy light. These results are explained using
      the calculated stabilities of the two possible products, together with the
      molecular orbitals involved in the lowest energy excited state.

PMID- 24124933
TI  - Patient information leaflet on mastoid surgery risks: assessment of readability
      and patient understanding.
AB  - INTRODUCTION: It is important that patients have a good understanding of surgery
      related risks, particularly for mastoid surgery, which exposes patients to the
      risk of very serious complications, despite addressing conditions which often
      have only minor symptoms. MATERIALS AND METHODS: A patient information leaflet
      describing the risks of mastoid surgery was prepared. However, the Hospital
      Patient Advice and Liaison Services team thought it was too long and complicated.
      It was introduced unchanged. Fifty-four consecutive mastoidectomy patients were
      given a questionnaire asking for their opinion of the leaflet. The leaflet was
      also assessed with readability formulae and the Ensuring Quality Information for
      Patients tool. RESULTS AND ANALYSIS: Ninety-eight per cent of respondents thought
      the leaflet's writing style was easy to understand. The majority (96 per cent)
      thought the length was 'just right'. The 7 readability formulae used established
      readability at a grade 9 level (i.e. appropriate for a reading age of 13-15
      years). The Ensuring Quality Information for Patients score was 87.5 per cent.
      DISCUSSION: Despite the drive to simplify patient information leaflets, quite
      detailed information is sometimes required. A style which is too simple may be
      perceived as patronising and may encourage patients to underestimate potential
      risks. It is important to ask patients their opinion.

PMID- 24124932
TI  - RNA-Seq analysis identifies a novel set of editing substrates for human ADAR2
      present in Saccharomyces cerevisiae.
AB  - ADAR2 is a member of a family of RNA editing enzymes found in metazoa that bind
      double helical RNAs and deaminate select adenosines. We find that when human
      ADAR2 is overexpressed in the budding yeast Saccharomyces cerevisiae it
      substantially reduces the rate of cell growth. This effect is dependent on the
      deaminase activity of the enzyme, suggesting yeast transcripts are edited by
      ADAR2. Characterization of this novel set of RNA substrates provided a unique
      opportunity to gain insight into ADAR2's site selectivity. We used RNA-Seq. to
      identify transcripts present in S. cerevisiae subject to ADAR2-catalyzed editing.
      From this analysis, we identified 17 adenosines present in yeast RNAs that
      satisfied our criteria for candidate editing sites. Substrates identified include
      both coding and noncoding RNAs. Subsequent Sanger sequencing of RT-PCR products
      from yeast total RNA confirmed efficient editing at a subset of the candidate
      sites including BDF2 mRNA, RL28 intron RNA, HAC1 3'UTR RNA, 25S rRNA, U1 snRNA,
      and U2 snRNA. Two adenosines within the U1 snRNA sequence not identified as
      substrates during the original RNA-Seq. screen were shown to be deaminated by
      ADAR2 during the follow-up analysis. In addition, examination of the RNA sequence
      surrounding each edited adenosine in this novel group of ADAR2 sites revealed a
      previously unrecognized sequence preference. Remarkably, rapid deamination at one
      of these sites (BDF2 mRNA) does not require ADAR2's dsRNA-binding domains
      (dsRBDs). Human glioma-associated oncogene 1 (GLI1) mRNA is a known ADAR2
      substrate with similar flanking sequence and secondary structure to the yeast
      BDF2 site discovered here. As observed with the BDF2 site, rapid deamination at
      the GLI1 site does not require ADAR2's dsRBDs. 

PMID- 24124934
TI  - Freedom of speech and science: can companies force us to withdraw data they don't
      like?

PMID- 24124935
TI  - Morphological pattern classification system for plantar thermography of patients
      with diabetes.
AB  - BACKGROUND: A plantar temperature distribution can be obtained by thermography;
      however, the advantage has not been effectively utilized in the past. We
      previously proposed a classification method based on the angiosome concept, but
      the method was insufficient because it was too subjective and complicated for
      clinicians. In this study, we propose a new classification system of plantar
      forepart thermographic patterns using an image segmentation technique. METHODS: A
      cross-sectional observational study was conducted including 32 healthy volunteers
      and 129 patients with diabetes mellitus (DM). Individual thermographic variations
      and trends were evaluated. A comparison was conducted between the patterns
      obtained by our previous angiosome-based research and the patterns found by the
      new classification system. RESULTS: The system objectively found wider variations
      of the plantar forepart thermographic patterns in the patients with DM compared
      with those in the control subjects. In patients with DM, the system showed that
      the whole-high pattern was most frequent (46%), followed by the butterfly pattern
      (12%). In the control group, the butterfly pattern was most frequent (44%),
      followed by the whole-high pattern (19%). Both ankle and toe brachial indices
      were higher in feet with high temperature area in the inner side of the plantar.
      CONCLUSIONS: Thermographic patterns found by the new computer-based system were
      similar to those obtained in our previous subjective work. The classification
      system found forefoot-low pattern and tiptoe-low pattern objectively. The system
      based on infrared thermography will be a screening tool to assess circulatory
      status in daily foot care of patients with DM.

PMID- 24124936
TI  - Plantar pressure distribution patterns of individuals with prediabetes in
      comparison with healthy individuals and individuals with diabetes.
AB  - BACKGROUND: Since elevated mechanical stress along with loss of plantar
      protective sensation are considered relevant factors in skin breakdown resulting
      in diabetic foot ulcerations, the assessment of plantar pressure is important for
      the prevention of diabetic foot complications. Prediabetes subjects are at risk
      of chronic hyperglycemia complications, among them neuropathy, but information
      about plantar loading in this population is not available. We aimed to compare
      baropodometric parameters of individuals with prediabetes versus healthy persons
      and persons with diabetes mellitus (DM). METHODS: Baropodometric data from 73
      subjects (15 with prediabetes (pre-DM), 28 with type 2 DM, 30 healthy) aged
      between 29 and 69 years of both genders were registered through a pressure
      platform with self-selected gait speed and first-step protocol. Peak plantar
      pressure, stance time, percentage of contact time, percentage of contact area and
      pressure-time integral were assessed in five plantar foot regions: heel, midfoot,
      metatarsals, hallux, and toes 2 to 5. Groups were compared by one-way analysis of
      variance with Scheffe post hoc (alpha = 0.05). RESULTS: Age, body mass index,
      gender, and arch height index did not differ between groups. Pre-DM and DM
      subjects presented increased peak pressure and pressure-time integral in
      metatarsals (p = .010; p > .001), as well as increased percentage of contact time
      in midfoot (p = .006) and metatarsals (p = .004) regions when compared with
      healthy subjects. Stance time was significantly higher (p = .017) in DM subjects.
      CONCLUSIONS: Pre-DM subjects seem to exhibit an altered plantar pressure
      distribution pattern similar to that often found in DM subjects.

PMID- 24124937
TI  - Infrared thermal imaging for automated detection of diabetic foot complications.
AB  - BACKGROUND: Although thermal imaging can be a valuable technology in the
      prevention and management of diabetic foot disease, it is not yet widely used in
      clinical practice. Technological advancement in infrared imaging increases its
      application range. The aim was to explore the first steps in the applicability of
      high-resolution infrared thermal imaging for noninvasive automated detection of
      signs of diabetic foot disease. METHODS: The plantar foot surfaces of 15 diabetes
      patients were imaged with an infrared camera (resolution, 1.2 mm/pixel): 5
      patients had no visible signs of foot complications, 5 patients had local
      complications (e.g., abundant callus or neuropathic ulcer), and 5 patients had
      diffuse complications (e.g., Charcot foot, infected ulcer, or critical ischemia).
      Foot temperature was calculated as mean temperature across pixels for the whole
      foot and for specified regions of interest (ROIs). RESULTS: No differences in
      mean temperature >1.5  degrees C between the ipsilateral and the contralateral
      foot were found in patients without complications. In patients with local
      complications, mean temperatures of the ipsilateral and the contralateral foot
      were similar, but temperature at the ROI was >2  degrees C higher compared with
      the corresponding region in the contralateral foot and to the mean of the whole
      ipsilateral foot. In patients with diffuse complications, mean temperature
      differences of >3  degrees C between ipsilateral and contralateral foot were
      found. CONCLUSIONS: With an algorithm based on parameters that can be captured
      and analyzed with a high-resolution infrared camera and a computer, it is
      possible to detect signs of diabetic foot disease and to discriminate between no,
      local, or diffuse diabetic foot complications. As such, an intelligent
      telemedicine monitoring system for noninvasive automated detection of signs of
      diabetic foot disease is one step closer. Future studies are essential to confirm
      and extend these promising early findings.

PMID- 24124938
TI  - Repeatability of infrared plantar thermography in diabetes patients: a pilot
      study.
AB  - OBJECTIVE: Infrared (IR) thermography has been used as a complementary diagnostic
      method in several pathologies, including distal diabetic neuropathy, by tests
      that induce thermoregulatory responses, but nothing is known about the
      repeatability of these tests. This study aimed to assess the repeatability of the
      rewarming index in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic
      control subjects. METHODS: Using an IR camera, plantar IR images were collected
      at baseline (pre-) and 10 min after (post-) cold stress testing on two different
      days with 7 days interval. Plantar absolute average temperatures pre- and post
      cold stress testing, the difference between them (DeltaT), and the rewarming
      index were obtained and compared between days. Repeatability of the rewarming
      index after the cold stress test was assessed by Bland-Altman plot limits of
      agreement. RESULTS: Ten T2DM subjects and ten nondiabetic subjects had both feet
      analyzed. Mean age did not differ between groups (p = .080). Absolute average
      temperatures of plantar region pre- (p = .033) and post-cold stress test (p =
      .019) differed between days in nondiabetic subjects, whereas they did not differ
      in T2DM subjects (pretest, p = .329; post-test, p = .540). DeltaT and rewarming
      index did not differ between days for both groups, and the rewarming index
      presented a 100% agreement of day-to-day measurements from T2DM subjects and 95%
      with nondiabetic subjects. CONCLUSIONS: The rewarming index after cold stress
      testing presented good repeatability between two days a week in both groups.
      Despite T2DM subjects presenting no differences on absolute temperature values
      between days, DeltaT or rewarming index after cold stress testing remain
      recommended beside absolute temperature values for clinical use.

PMID- 24124939
TI  - Diabetic peripheral neuropathy and gait: does footwear modify this association?
AB  - BACKGROUND: Gait-related fall risk is the leading cause of mortality among
      patients with diabetes, especially those older than 65 years. Deterioration in
      balance and loss of protective sensation in lower extremities contribute
      significantly to fall risk in patients with diabetic peripheral neuropathy (DPN).
      This study aimed to explore the impact of neuropathy and foot ulcer on gait.
      METHODS: We recruited 39 participants (age, 56.9 +/- 8.2 years; body mass index,
      29.6.3 +/- 4.7 kg/m2), including 15 DPN patients without foot ulcers, 16 DPN
      patients with foot ulcers, and 8 healthy aged-matched controls. Patients with
      active foot ulcers wore an offloading device during gait examination, including
      removable cast walker. RESULTS: Results suggest that neuropathy alters gait
      mainly by increasing gait initiation, gait variability (coefficient of variation
      of gait velocity), and double support (DS) time, while reducing knee range of
      motion and center of mass sway (p < .05). Interestingly, the presence of foot
      ulcer does not impact gait velocity (p > .1) but enhances some of the gait
      parameters such as gait variability and DS time. CONCLUSIONS: This study
      demonstrates that neuropathy deteriorates gait, but the presence of foot ulcers
      does not alter gait parameters further than neuropathy. In addition, patients
      with foot ulcers demonstrated a better gait compared with DPN patients without
      ulcers. We speculate that offloading footwear may be enhancing the somatosensory
      feedback from sensate skin, thereby positively affecting gait parameters. A study
      with a larger sample is required to explore the effect of prescribed footwear in
      the DPN population in order to validate the findings of this research study.

PMID- 24124940
TI  - Novel wearable technology for assessing spontaneous daily physical activity and
      risk of falling in older adults with diabetes.
AB  - BACKGROUND: As baby boomers age and their expected life span increases, there is
      an unprecedented need to better manage the health care of elders with diabetes
      who are at increased risk of falling due to diabetes complications, frailty, or
      other conditions. New clinical and research tools are needed to measure
      functioning accurately and to identify early indicators of risk of falling, thus
      translating into more effective and earlier intervention. METHODS: The objective
      of this pilot study was to validate a significant change in hardware and
      algorithm to track activity patterns using a single triaxial accelerometer
      through validation of timed up and go and standard measures of balance and gait.
      We recruited a convenience sample of eight older adults with diabetes and
      peripheral neuropathy (age, 77 +/- 7 years old) who were asked to wear the sensor
      for imposed daytime activity performed in our gait laboratory. Subjects were
      stratified into risk of falling categories based on Tinetti scores. We examined
      the accuracy of the suggested technology for discrimination of high- versus low
      risk groups. RESULTS: The system was accurate in identifying the number of steps
      taken and walking duration (random error <5%). The proposed algorithm allowed
      accurate identification and stratification of those at highest risk of falling,
      suggesting that subjects with high risk of falling required a substantially
      longer duration for rising from a chair when compared with those with low risk of
      falling (p < .05). CONCLUSIONS: Our new single triaxial accelerometer algorithm
      successfully tracked postural transition, allowing accurate identification of
      those at high risk of falling, and could be useful for intermittent or even
      continuous monitoring of older adults with diabetes. Other potential applications
      could include activity monitoring of the diabetes population with lower extremity
      disease and of patients undergoing surgical procedures or as an objective measure
      during rehabilitation.

PMID- 24124941
TI  - Validation of a laser-assisted wound measurement device for measuring wound
      volume.
AB  - BACKGROUND: Accurate and precise wound measurement is an essential part of the
      medical record when monitoring a patient with a chronic wound. This study was
      designed to determine if a new device, a laser-assisted wound measurement (LAWM)
      device, provides valid measurements for wound area, depth, and volume. METHODS:
      We compared four methods to evaluate the area and volume of 12 wounds of
      differing size and depth that were created on the dorsum of a sacrificed pig. We
      evaluated the LAWM device, digital photograph assessment with National Institutes
      of Health ImageJ software, measurements of depth with a ruler, and weight-to
      volume assessment with dental paste. We then sought to cross validate this data
      with further analyses obtained from these measurements using a Play-Doh(r)-based
      wound as a model for constant area with different depths. RESULTS: We demonstrate
      that the LAWM device measures wound area accurately. Depth (and therefore volume)
      measurements, however, are artificially low. This inaccuracy is the same for
      shallow and deep wounds. CONCLUSIONS: The inaccuracy in the depth and volume
      measurements with the LAWM device results in an artificially low measurement.
      However, this may not affect percentage difference measurements. Further studies
      will need to be performed to determine if this device can accurately determine
      wound changes in the clinical setting.

PMID- 24124942
TI  - Validation of plantar pressure measurements for a novel in-shoe plantar sensory
      replacement unit.
AB  - BACKGROUND: Research concerning prevention of diabetic foot complications is
      critical. A novel in-shoe plantar sensory replacement unit (PSRU) has been
      developed that provides alert-based feedback derived from analyzing plantar
      pressure threshold measurements in real time. The purpose of this study was to
      compare the PSRU device to a gold standard pressure-sensing device (GS-PSD) to
      determine the correlation between concurrent measures of plantar pressure during
      walking. METHODS: The PSRU had an array of eight sensors with a range of 10-75 mm
      Hg and collected data at 4 Hz, whereas the GS-PSD had 99 sensors with a range of
      1-112 mm Hg and collected data at 100 Hz. Based on an a priori power analysis,
      data were collected from 10 participants (3 female, 7 male) while walking over
      ground in both devices. The primary variable of interest was the number of data
      points recorded that were greater than 32 mm Hg (capillary arterial pressure--the
      minimum pressure reported to cause pressure ulcers) for each of the eight PSRU
      sensors and corresponding average recordings from the GS-PSD sensor clusters.
      Intraclass correlation coefficient (2,1) was used to compare data between the two
      devices. RESULTS: Compared with the GS-PSD, we found good-to-very-good
      correlations (r-value range 0.67-0.86; p-value range 0.01-0.05) for six of the
      PSRU's eight sensors and poor correlation for only two sensors (r = 0.41, p =
      .15; r = 0.38, p = .18) when measuring the number of data points recorded that
      were greater than 32 mm Hg. CONCLUSIONS: Based on the results of the present
      study, we conclude the PSRU provides analogous data when compared with a GS-PSD.

PMID- 24124943
TI  - Validation of plantar pressure measurements for a novel in-shoe plantar sensory
      replacement unit.
AB  - An article by Ferber and coauthors in Journal of Diabetes Science and Technology
      reported on the ability of a novel in-shoe plantar sensory replacement unit
      (PSRU) to provide alert-based feedback derived from analyzing plantar pressure
      (PP) threshold measurements in real time. The study aimed at comparing the PSRU
      device to a gold standard pressure-sensing device (GS-PSD) to determine the
      correlation between concurrent measures of PP during walking. Data were collected
      simultaneously from 10 participants who walked overground with both devices. The
      variable of interest was the number of recorded data points greater than 32 mmHg
      for each of the PSRU sensors and corresponding average recordings from the GS
      PSD. Authors concluded that the PSRU provides analogous data to the GS-PSD.
      However, several aspects of the study should be considered when interpreting
      their clinical relevance. 

PMID- 24124944
TI  - Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot.
AB  - Accurate detection and quantification of human diabetic peripheral neuropathy are
      important to define at-risk patients, anticipate deterioration, and assess new
      therapies. Easily performed clinical techniques such as neuro-logical
      examination, assessment of vibration perception or insensitivity to the 10 g
      monofilament only assess advanced neuropathy, i.e., the at-risk foot. Techniques
      that assess early neuropathy include neurophysiology (which assesses only large
      fibers) and quantitative sensory testing (which assesses small fibers), but they
      can be highly subjective while more objective techniques, such as skin biopsy for
      intra-epidermal nerve fiber density quantification, are invasive and not widely
      available. The emerging ophthalmic technique of corneal confocal microscopy
      allows quantification of corneal nerve morphology and enables clinicians to
      diagnose peripheral neuropathy in diabetes patients, quantify its severity, and
      potentially assess therapeutic benefit. The present review provides a detailed
      critique of the rationale, a practical approach to capture images, and a basis
      for analyzing and interpreting the images. We also critically evaluate the
      diagnostic ability of this new noninvasive ophthalmic test to diagnose diabetic
      and other peripheral neuropathies. 

PMID- 24124945
TI  - Applying 21st century imaging technology to wound healing: an Avant-Gardist
      approach.
AB  - A significant arising complication in the care of patients with diabetes is
      increased susceptibility to chronic wounds, including diabetic foot ulcers and
      pressure sores. This is driven by, e.g., neuropathy and peripheral arterial
      disease. It is well recognized that best practice in wound care requires wound
      assessment, including measurement, on presentation and regularly throughout the
      treatment program. Proper assessment is necessary to ensure that the most
      appropriate and cost-effective therapy is used at all times, with quantitative
      measurement necessary to track the efficacy of the chosen approach. A documented
      assessment can also assist patient-clinician dialog and discussion within the
      multidisciplinary team. Remote evaluation and assessment of the wound is also of
      increasing importance and practicality through the use of a telemedicine
      approach. There has been considerable progress in the space of imaging for
      wounds, including systems that include three-dimensional measurement and
      telemedicine features. This literature review examines the available options and
      reviews the clinical evidence for measurement accuracy, scope for remote
      assessment, and published user feedback on the systems. 

PMID- 24124946
TI  - Reconsidering nerve decompression: an overlooked opportunity to limit diabetic
      foot ulcer recurrence and amputation.
AB  - Nerve decompression for relief of subjective diabetic sensorimotor polyneuropathy
      pain and numbness has been labeled of "unknown" benefit. Objective outcomes in
      treatment and prevention of diabetic foot complications are reviewed. There is
      growing evidence that plantar foot ulceration and recurrence in high-risk feet
      are minimized with this operation. Avoiding neuropathic and neuroischemic ulcer
      wounds should theoretically reduce amputations and perhaps mortality risk.
      Protective effects are hypothesized to act via relief of neuro-vascular
      entrapment, thereby improving neurally modulated tissue homeostasis factors.
      Nerve decompression deserves considerable research attention to understand its
      role in limiting foot complications. Its apparent benefits challenge the paradigm
      that diabetic neuropathy is a purely length-dependent axonopathy and may
      necessitate appreciation of superimposed nerve entrapment as an significant
      operant factor.

PMID- 24124947
TI  - Electrical stimulation as an adjunctive treatment of painful and sensory diabetic
      neuropathy.
AB  - BACKGROUND: The objective of this review is to evaluate the use of electrical
      stimulation to treat diabetic neuropathy. Application of electrical stimulation
      may provide a novel treatment option for large and small fiber neuropathy in
      persons with diabetes. Large and small nerve neuropathy alters pain,
      proprioception, touch perception, and motor function, which cause burning foot
      pain and serve as protective mechanisms from ulcerations. METHODS: A content
      search for clinical trials involving electrical stimulation, neuropathy, and
      diabetes was conducted through PubMed. Randomized clinical trials and prospective
      studies with outcome measures affecting the lower extremity function were
      selected for review. RESULTS: We identified eight studies in which electrical
      stimulation was used to treat diabetic neuropathy. Six studies evaluated small
      fiber neuropathy. Two studies evaluated patients with both small and large fiber
      neuropathy and reported significant improvement in vibration and monofilament
      testing and reduction in symptoms in the electrical stimulation treatment group.
      Six of the eight painful neuropathy studies identified significant improvement in
      symptoms. There were no studies that evaluated electrical stimulation to treated
      diabetic motor neuropathy, fall prevention or postural instability. CONCLUSIONS:
      Electrical stimulation may be an effective alternative and adjunctive therapy to
      current interventions for diabetic peripheral neuropathy.

PMID- 24124948
TI  - Continuous glucose monitoring in the subcutaneous tissue over a 14-day sensor
      wear period.
AB  - BACKGROUND: Glucose monitoring systems using subcutaneously inserted sensors are
      currently labeled for up to 7 days of wear. In this study, we evaluated the
      feasibility of a 14-day wear duration using a modified version of the sensor
      found in the Freestyle NavigatorTM continuous glucose monitoring system. METHODS:
      Sixty-two subjects with diabetes were enrolled in the study. One sensor per
      subject was inserted on the arm for a wear time of 14 days. Two different
      calibration algorithms were applied retrospectively, one that uses periodic
      sensor recalibrations and one without recalibrations. Sensor in vivo stability
      was determined by least square regression analysis using capillary blood glucose.
      Mean absolute relative difference (MARD) and mean relative difference were
      calculated. Consensus error grid analysis was performed by day and over the 14
      day wear period to evaluate accuracy of both systems. The sensor insertion sites
      were inspected after sensor removal for skin reactions. RESULTS: Sensor data from
      55 subjects were used for the analysis. The accuracy metrics for the system with
      recalibration were calculated to MARD = 13.9% and 84.0% in zone A (error grid
      analysis). The system without recalibration performed significantly better,
      resulting in MARD of 12.2% and 88.0% in zone A (p < .0001). The maximum change of
      in vivo sensor sensitivity over the 14-day wear period was 2% per day. Two
      subjects reported pain during the first 5 days of sensor wear, and 1 subject
      reported itching at the sensor site. No further skin reactions were noticed.
      CONCLUSIONS: The study shows that a 14-day sensor wear period is achievable.
      Moreover, sensors using "wired enzyme" technology showed excellent in vivo
      stability, with no significant sensitivity loss over the 14-day wear period.

PMID- 24124949
TI  - Retrospective outcomes of glucose control in critically ill children.
AB  - BACKGROUND: Hyperglycemia is a significant problem for critically ill children.
      Treatment for hyperglycemia remains controversial. This study explores the effect
      of controlling blood glucose (BG) in hyperglycemic critically ill children.
      METHODS: A retrospective cohort of nondiabetic critically ill children (defined
      as requiring mechanical ventilation and/or vasopressors) with BG persistently >=
      150 mg/dl and treated with insulin (treatment group) were compared with a
      historical cohort of similar children who did not receive interventions to
      control hyperglycemia (baseline group). RESULTS: There were 130 children in the
      treatment group and 137 children in the baseline group. Mean BG in the treatment
      group was 140 +/- 24 mg/dl compared with 179 +/- 47 mg/dl in the baseline group
      (p < .001). After adjusting for patient characteristics, cointerventions, and
      glucose metrics, patients in the treatment group had 2.5 fewer intensive care
      unit (ICU)-free days (i.e., number of days alive and discharged from ICU within
      28 days after inclusion) than the baseline group (p = .023). Glucose control was
      not independently associated with duration of ICU stay, ventilator-free days,
      vasopressor-free days, or mortality. CONCLUSIONS: Blood glucose control appears
      associated with worse outcomes in critically ill children. Our data combined with
      conflicting results in adults leads us to strongly advocate for the conduct of
      randomized trials on glucose control in critically ill children.

PMID- 24124950
TI  - Association of self-monitoring of blood glucose use on glycated hemoglobin and
      weight in newly diagnosed, insulin-naive adult patients with type 2 diabetes.
AB  - BACKGROUND: Clinical trials have shown that self-monitoring of blood glucose
      (SMBG) combined with patient education and medication titration can lead to
      improved glycated hemoglobin (HbA1c) and reduced weight in recently diagnosed non
      insulin-treated type 2 diabetes mellitus (T2DM) patients. This retrospective
      matched cohort study assessed the association of SMBG with achieving long-term
      clinical outcomes in these patients in a real-world clinical setting. METHODS:
      Using electronic medical records (2008-2011), we selected a population of adult
      patients recently diagnosed with T2DM not receiving insulin who were SMBG users
      and a population of non-SMBG controls with similar demographic and clinical
      characteristics using propensity score matching. The main study outcomes compared
      between the two groups were time to achieve (1) HbA1c <7% for patients with
      baseline HbA1c >= 7% and (2) a >= 5% reduction in weight from baseline. RESULTS:
      Of the 589 patients identified in each group, 113 in each group had a baseline
      HbA1c >= 7% (mean, 8.2%). The SMBG users were more likely to achieve an HbA1c <7%
      (12 months: 58.4% versus 38.9%, p = .0037; 36 months: 84.0% versus 70.0%, p =
      .0013) and to do so faster (median, 6.5 versus 20.5 months; log-rank p = .0016).
      Self-monitoring of blood glucose was associated with faster weight reduction
      (median time to achieve a >= 5% reduction, 23.5 versus 35.9 months for SMBG and
      non-SMBG, respectively; log-rank p = .0005). CONCLUSIONS: In newly diagnosed T2DM
      insulin-naive patients, SMBG users had an improved rate of achieving long-term
      glycemic control and weight loss in a real-world clinical setting.

PMID- 24124951
TI  - Using simulation technology to teach diabetes care management skills to resident
      physicians.
AB  - BACKGROUND: Simulation is widely used to teach medical procedures. Our goal was
      to develop and implement an innovative virtual model to teach resident physicians
      the cognitive skills of type 1 and type 2 diabetes management. METHODS: A
      diabetes educational activity was developed consisting of (a) a curriculum using
      18 explicit virtual cases, (b) a web-based interactive interface, (c) a
      simulation model to calculate physiologic outcomes of resident actions, and (d) a
      library of programmed feedback to critique and guide resident actions between
      virtual encounters. Primary care residents in 10 U.S. residency programs received
      the educational activity. Satisfaction and changes in knowledge and confidence in
      managing diabetes were analyzed with mixed quantitative and qualitative methods.
      RESULTS: Pre- and post-education surveys were completed by 92/142 (65%) of
      residents. Likert scale (five-point) responses were favorably higher than neutral
      for general satisfaction (94%), recommending to colleagues (91%), training
      adequacy (91%), and navigation ease (92%). Finding time to complete cases was
      difficult for 50% of residents. Mean ratings of knowledge (on a five-point scale)
      posteducational activity improved by +0.5 (p < .01) for use of all available drug
      classes, +0.9 (p < .01) for how to start and adjust insulin, +0.8 (p < .01) for
      interpreting blood glucose values, +0.8 (p < .01) for individualizing treatment
      goals, and +0.7 (p < .01) for confidence in managing diabetes patients.
      CONCLUSIONS: A virtual diabetes educational activity to teach cognitive skills to
      manage diabetes to primary care residents was successfully developed,
      implemented, and well liked. It significantly improved self-assessed knowledge
      and confidence in diabetes management.

PMID- 24124952
TI  - Model-based closed-loop glucose control in type 1 diabetes: the DiaCon
      experience.
AB  - BACKGROUND: To improve type 1 diabetes mellitus (T1DM) management, we developed a
      model predictive control (MPC) algorithm for closed-loop (CL) glucose control
      based on a linear second-order deterministic-stochastic model. The deterministic
      part of the model is specified by three patient-specific parameters: insulin
      sensitivity factor, insulin action time, and basal insulin infusion rate. The
      stochastic part is identical for all patients but identified from data from a
      single patient. Results of the first clinical feasibility test of the algorithm
      are presented. METHODS: We conducted two randomized crossover studies. Study 1
      compared CL with open-loop (OL) control. Study 2 compared glucose control after
      CL initiation in the euglycemic (CL-Eu) and hyperglycemic (CL-Hyper) ranges,
      respectively. Patients were studied from 22:00-07:00 on two separate nights.
      RESULTS: Each study included six T1DM patients (hemoglobin A1c 7.2% +/- 0.4%). In
      study 1, hypoglycemic events (plasma glucose < 54 mg/dl) occurred on two OL and
      one CL nights. Average glucose from 22:00-07:00 was 90 mg/dl [74-146 mg/dl;
      median (interquartile range)] during OL and 108 mg/dl (101-128 mg/dl) during CL
      (determined by continuous glucose monitoring). However, median time spent in the
      range 70-144 mg/dl was 67.9% (3.0-73.3%) during OL and 80.8% (70.5-89.7%) during
      CL. In study 2, there was one episode of hypoglycemia with plasma glucose <54
      mg/dl in a CL-Eu night. Mean glucose from 22:00-07:00 and time spent in the range
      70-144 mg/dl were 121 mg/dl (117-133 mg/dl) and 69.0% (30.7-77.9%) in CL-Eu and
      149 mg/dl (140-193 mg/dl) and 48.2% (34.9-72.5%) in CL-Hyper, respectively.
      CONCLUSIONS: This study suggests that our novel MPC algorithm can safely and
      effectively control glucose overnight, also when CL control is initiated during
      hyperglycemia.

PMID- 24124953
TI  - Evaluation of point-of-care blood glucose measurements in patients with diabetic
      ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care
      unit.
AB  - BACKGROUND: Point-of-care (POC) blood glucose (BG) measurement is currently not
      recommended in the treatment of patients presenting with diabetic ketoacidosis
      (DKA) or hyperglycemic hyperosmolar syndrome (HHS). METHODS: We prospectively
      evaluated and compared capillary and venous POC BG values with laboratory venous
      glucose in patients with DKA or HHS admitted to one critical care unit over 8
      months. RESULTS: Venous laboratory glucose was strongly correlated with venous (r
      = 0.98) and capillary (r = 0.96) POC glucose values, though POC glucose values
      were higher than venous laboratory values (venous POC 21 +/- 3 mg/dl, capillary
      POC 30 +/- 4 mg/dl; both p < .001). Increased plasma osmolality had no effect on
      glucose meter error, while acidemia (pH < 7.3) was associated with greater
      glucose meter error (p = .04) independent of glucose levels. Comparing
      hypothetical insulin infusion rates based on laboratory venous glucose to actual
      infusion rates based on POC glucose values showed that 33/61 insulin infusion
      rates would have been unchanged, while 28 out of 61 rates were on average 7% +/-
      2% higher. There were no instances of hypoglycemia in any of the patients.
      CONCLUSIONS: Overall, both venous and capillary POC BG values were safe for the
      purpose of titrating insulin infusions in patients with severe hyperglycemia.
      Acidemia, but not hyperosmolality, increased POC BG value errors.

PMID- 24124954
TI  - Technical aspects of the Parkes error grid.
AB  - BACKGROUND: The Parkes error grid, which was developed in 1994, presented
      performance zones for blood glucose (BG) monitors with borders that were not
      mathematically specified at the time the grid was published. METHODS: In this
      article, we (1) review the history of the Parkes error grid, (2) present the
      never-before-published exact coordinates and specifications of the grid so that
      others may produce an exact replica of the original grid, and (3) discuss our
      suggestions how this metric should be applied. RESULTS: The new ISO15197:2013
      guideline for system accuracy assessment of BG meters for patient self
      measurement incorporates use of this metric for defining acceptable accuracy of
      BG monitors. It is expected that, for regulatory purposes, this document will
      stipulate that the error grid version for type 1 diabetes should be applied with
      the caveat that only the A zone represents acceptable accuracy. CONCLUSIONS: It
      remains to be seen by how much the new error grid, which is currently being
      developed by the Food and Drug Administration/Diabetes Technology
      Society/American Diabetes Association/The Endocrine Society/Association for
      Advancement of Medical Instrumentation, will deviate from the Parkers error grid.

PMID- 24124955
TI  - Analytic evaluation of a new glucose meter system in 15 different critical care
      settings.
AB  - BACKGROUND: Maintaining appropriate glycemic control in critically ill patients
      reduces morbidity and mortality. The use of point-of-care (POC) glucose devices
      is necessary to obtain rapid results at the patient's bedside. However, the
      devices should be thoroughly tested in the intended population before
      implementation. The use of POC glucose meters in critically ill patients has been
      questioned both in the literature and by regulatory agencies. The aim of this
      study was to determine if the ACCU-CHEK(r) Inform II system (Roche Diagnostics)
      POC glucose meter demonstrated the desired accuracy and precision, as defined by
      Clinical and Laboratory Standards Institute guideline POCT12-A3, in a large
      number of critically ill patients from multiple intensive care settings at two
      academic medical centers. METHODS: A total of 1200 whole blood meter results from
      600 patients were compared with central laboratory plasma values. Whole blood
      aliquots from venous samples were used to obtain duplicate meter results with the
      remaining sample being processed to obtain plasma for central laboratory testing
      within 5 min of meter testing. RESULTS: A total of 1185 (98.8%) of the new
      meter's glucose values were within +/- 12.5% (+/- 12 mg/dl for values >= 100
      mg/dl) of the comparative laboratory glucose values, and 1198 (99.8%) were within
      +/- 20% (+/- 20 mg/dl for values <100 mg/dl). CONCLUSIONS: Considering the large
      number of patients from numerous critical care units examined, the new glucose
      meter system appears to have sufficient analytic accuracy for use in critically
      ill patients.

PMID- 24124956
TI  - Analysis: New point-of-care blood glucose monitoring system for the hospital
      demonstrates satisfactory analytical accuracy using blood from critically ill
      patients--an important step toward improved blood glucose control in the
      hospital.
AB  - Patients managed in the intensive care units (ICUs) and general wards of the
      hospital experience a high incidence of hyperglycemia, hypoglycemia, and glycemic
      variability, despite significant hospital resources devoted to glucose control.
      Optimized glucose meters and monitoring systems are required to improve the
      safety and efficacy of insulin delivery and glucose control in the hospital. Safe
      insulin dosing requires timely and accurate glucose measurements, especially
      during dynamic changes in nutrition, insulin sensitivity, and physiological
      stress. In the current issue of Journal of Diabetes Science and Technology,
      Mitsios and coauthors describe the analytical accuracy of the new Accu-Check(r)
      Inform II blood glucose (BG) monitoring system commercialized by F. Hoffmann-La
      Roche Ltd. The point-of-care glucose meter achieved the desired degree of
      accuracy and precision, as defined by Clinical and Laboratory Standards Institute
      POCT12-A3 guidelines when evaluated using venous blood from 600 critically ill
      patients from multiple ICUs at two medical centers. Venous whole blood samples
      were used to obtain glucose meter results in duplicate. The remaining blood
      sample was centrifuged to obtain plasma for central hospital laboratory testing
      using the hexokinase method within 5 min of meter testing. A total of 98.8% of
      the 1200 Accu-Check Inform II meter's glucose values were within +/- 12.5% (+/-
      12 mg/dl) of the mean laboratory glucose value, and 99.8% were within +/- 20% (+/
      20 mg/dl), thus meeting the Clinical and Laboratory Standards Institute
      criteria. Future studies are required to evaluate the clinical performance of the
      new BG monitoring system in the intended-use patient populations and critical
      care environments, using arterial, peripheral venous, central venous, and
      capillary blood samples.

PMID- 24124957
TI  - Accuracy evaluation of five blood glucose monitoring systems: the North American
      comparator trial.
AB  - BACKGROUND: This study evaluated differences in accuracy between the CONTOUR(r)
      NEXT EZ (EZ) blood glucose monitoring system (BGMS) and four other BGMSs [ACCU
      CHEK(r) Aviva (ACAP), FreeStyle Freedom Lite(r) (FFL), ONE TOUCH(r) Ultra(r)2
      (OTU2), and TRUEtrack(r) (TT)]. METHODS: Up to three capillary blood samples (N =
      393) were collected from 146 subjects with and without diabetes. One sample per
      subject was tested with fresh (natural) blood; the other samples were glycolyzed
      to lower blood glucose to <70 mg/dl. Meter results were compared with results
      from plasma from the same sample tested on a Yellow Springs Instruments (YSI)
      2300 STAT PlusTM glucose analyzer. Blood glucose monitoring system accuracy was
      compared using mean absolute relative difference (MARD; from laboratory reference
      method results) and other analyses. Separate analyses on fresh (natural) samples
      only were conducted to determine potential effects of glycolysis on MARD values
      of systems utilizing glucose-oxidase-based test strip chemistry. RESULTS: Across
      the tested glucose range, the EZ had the lowest MARD of 4.7%; the ACAP, FFL,
      OTU2, and TT had MARD values of 6.3%, 18.3%, 23.4%, and 26.2%, respectively. For
      samples with glucose concentrations <70 mg/dl, the EZ had the lowest MARD
      (0.65%), compared with the ACAP (2.5%), FFL (18.3%), OTU2 (22.4%), and TT (33.2%)
      systems. CONCLUSIONS: The EZ had the lowest MARD across the tested glucose ranges
      when compared with four other BGMSs when all samples were analyzed as well as
      when natural samples only were analyzed.

PMID- 24124958
TI  - Analysis of "Accuracy evaluation of five blood glucose monitoring systems: the
      North American comparator trial".
AB  - In an article in Journal of Diabetes Science and Technology, Halldorsdottir and
      coauthors examined the accuracy of five blood glucose monitoring systems (BGMSs)
      in a study sponsored by the manufacturer of the BGMS CONTOUR NEXT EZ (EZ) and
      found that this BGMS was the most accurate one. However, their findings must be
      viewed critically given that one of the BGMSs (ACCU-CHEK Aviva) was not compared
      against the reference measurement specified by its manufacturer, thus making it
      likely that it performed suboptimally. Also, the accuracy of the glucose-oxidase
      based ONE TOUCH Ultra2 and TRUEtrack BGMS is likely to have been underestimated
      because of the expected low oxygen level in the glycolysed blood samples used to
      test the performance of these BGMSs under hypoglycemic conditions. In conclusion,
      although this study shows that EZ is an accurate BGMS, comparisons between this
      and other BGMSs should be interpreted with caution. 

PMID- 24124959
TI  - Signal processing algorithms implementing the "smart sensor" concept to improve
      continuous glucose monitoring in diabetes.
AB  - Glucose readings provided by current continuous glucose monitoring (CGM) devices
      still suffer from accuracy and precision issues. In April 2013, we proposed a new
      conceptual architecture to deal with these problems and render CGM sensors
      algorithmically smarter, which consists of three modules for denoising,
      enhancement, and prediction placed in cascade to a commercial CGM sensor. The
      architecture was assessed on a data set consisting of 24 type 1 diabetes patients
      collected in four clinical centers of the AP@home Consortium (a European project
      of 7th Framework Programme funded by the European Committee). This article, as a
      companion to our prior publication, illustrates the technical details of the
      algorithms and of the implementation issues. 

PMID- 24124960
TI  - Multiplicative surrogate standard deviation: a group metric for the glycemic
      variability of individual hospitalized patients.
AB  - OBJECTIVE: Group metrics are described to quantify blood glucose (BG) variability
      of hospitalized patients. METHODS: The "multiplicative surrogate standard
      deviation" (MSSD) is the reverse-transformed group mean of the standard
      deviations (SDs) of the logarithmically transformed BG data set of each patient.
      The "geometric group mean" (GGM) is the reverse-transformed group mean of the
      means of the logarithmically transformed BG data set of each patient. Before
      reverse transformation is performed, the mean of means and mean of SDs each has
      its own SD, which becomes a multiplicative standard deviation (MSD) after reverse
      transformation. Statistical predictions and comparisons of parametric or
      nonparametric tests remain valid after reverse transformation. A subset of a
      previously published BG data set of 20 critically ill patients from the first 72
      h of treatment under the SPRINT protocol was transformed logarithmically. After
      rank ordering according to the SD of the logarithmically transformed BG data of
      each patient, the cohort was divided into two equal groups, those having lower or
      higher variability. RESULTS: For the entire cohort, the GGM was 106 (//* 1.07)
      mg/dl, and MSSD was 1.24 (//* 1.07). For the subgroups having lower and higher
      variability, respectively, the GGM did not differ, 104 (//* 1.07) versus 109 (//*
      1.07) mg/dl, but the MSSD differed, 1.17 (//* 1.03) versus 1.31 (//* 1.05), p =
      .00004. CONCLUSIONS: By using the MSSD with its MSD, groups can be characterized
      and compared according to glycemic variability of individual patient members.

PMID- 24124961
TI  - A novel insulin combination of insulin degludec and insulin aspart achieves a
      more stable overnight glucose profile than insulin glargine: results from
      continuous glucose monitoring in a proof-of-concept trial.
AB  - PURPOSE: Insulin degludec coformulated with insulin aspart (as IDegAsp) can cover
      24 h basal insulin and postprandial insulin requirements after a main meal with
      one injection. We compared glycemic stability following IDegAsp or insulin
      glargine (IGlar) given before the evening meal in patients with type 2 diabetes.
      METHODS: A subset of 112 insulin-naive type 2 diabetes patients from a
      randomized, parallel-group trial (IDegAsp versus IGlar, each added to metformin)
      underwent 72 h continuous interstitial glucose (IG) monitoring after 16 weeks of
      treatment. End points included mean IG concentrations, 2 h postprandial IG
      increments and postprandial peak, IG fluctuation (summed area above and below
      mean IG), within-subject coefficient of variation (day-to-day variation) in mean
      nocturnal IG, and episodes of low (<3.5 mmol/liter) and high (>10 mmol/liter) IG.
      Values were derived for the entire 72 h, with the nocturnal interval (0001-0559
      h) also assessed. RESULTS: The postdinner IG increment observed with IGlar did
      not occur with IDegAsp [IDegAsp - IGlar, -1.42 (-2.15, -0.70) mmol/liter].
      Nocturnal IG fluctuation was 21% lower with IDegAsp [IDegAsp/IGlar, 0.79 (0.66,
      0.96) mmol/liter], with 48% fewer nocturnal high IG episodes [ratio
      IDegAsp/IGlar, 0.52 (0.32, 0.87)]. CONCLUSIONS: IDegAsp given with the evening
      meal reduces postdinner glucose excursion and provides more stable nocturnal
      glycemia as compared with IGlar.

PMID- 24124962
TI  - Nocturnal continuous glucose and sleep stage data in adults with type 1 diabetes
      in real-world conditions.
AB  - BACKGROUND: Sleep plays an important role in health, and poor sleep is associated
      with negative impacts on diabetes management, but few studies have objectively
      evaluated sleep in adults with type 1 diabetes mellitus (T1DM). Nocturnal
      glycemia and sleep characteristics in T1DM were evaluated using body-worn sensors
      in real-world conditions. METHODS: Analyses were performed on data collected by
      the Diabetes Management Integrated Technology Research Initiative pilot study of
      17 T1DM subjects: 10 male, 7 female; age 19-61 years; T1DM duration 14.9 +/- 11.0
      years; hemoglobin A1c (HbA1c) 7.3% +/- 1.3% (mean +/- standard deviation). Each
      subject was equipped with a continuous glucose monitor and a wireless sleep
      monitor (WSM) for four nights. Sleep stages [rapid eye movement (REM), light, and
      deep sleep] were continuously recorded by the WSM. Nocturnal glycemia (mg/dl) was
      evaluated as hypoglycemia (<50 mg/dl), low (50-69 mg/dl), euglycemia (70-120
      mg/dl), high (121-250 mg/dl), and hyperglycemia (>250 mg/dl) and by several
      indices of glycemic variability. Glycemia was analyzed within each sleep stage.
      RESULTS: Subjects slept 358 +/- 48 min per night, with 85 +/- 27 min in REM
      sleep, 207 +/- 42 min in light sleep, and 66 +/- 30 min in deep sleep (mean +/-
      standard deviation). Increased time in deep sleep was associated with lower HbA1c
      (R2 = 0.42; F = 9.37; p < .01). Nocturnal glycemia varied widely between and
      within subjects. Glycemia during REM sleep was hypoglycemia 5.5% +/- 18.1%, low
      6.6% +/- 18.5%, euglycemia 44.6% +/- 39.5%, high 37.9% +/- 39.7%, and
      hyperglycemia 5.5% +/- 21.2%; glycemia during light sleep was hypoglycemia 4.8%
      +/- 12.4%, low 7.3% +/- 12.9%, euglycemia 42.1% +/- 33.7%, high 39.2% +/- 34.6%,
      and hyperglycemia 6.5% +/- 20.5%; and glycemia during deep sleep was hypoglycemia
      0.5% +/- 2.2%, low 5.8% +/- 14.3%, euglycemia 48.0% +/- 37.5%, high 39.5% +/-
      37.6%, and hyperglycemia 6.2% +/- 19.5%. Significantly less time was spent in the
      hypoglycemic range during deep sleep compared with light sleep (p = .02).
      CONCLUSIONS: Increased time in deep sleep was associated with lower HbA1c, and
      less hypoglycemia occurred in deep sleep in T1DM, though this must be further
      evaluated in larger subsequent studies. Furthermore, the consumer-grade WSM
      device was useful for objectively studying sleep in a real-world setting.

PMID- 24124963
TI  - Dose accuracy and injection force of different insulin glargine pens.
AB  - BACKGROUND: Dose accuracy and injection force, representing key parameters of
      insulin pens, were determined for three pens delivering insulin glargine-based
      copies, Pen Royale (WR) and DispoPen (WD) for Glaritus(r) (Wockhardt) and GanLee
      Pen (GL) for Basalin(r) (Gan & Lee), compared with pens of the originator,
      ClikSTAR(r) (CS) and SoloSTAR(r) (SS) for Lantus(r) (Sanofi). METHODS: Using the
      weighing procedure recommended by DIN EN ISO 11608-1:2000, dose accuracy was
      evaluated based on nonrandomized delivery of low (5 U), mid (30 U), and high (60
      U) dosage levels. Injection force was measured by dispensing the maximum dose of
      insulin (60 U for the GL, WR, and WD; 80 U for the SS and CS) at dose speeds of 6
      and 10 U/s. RESULTS: All tested pens delivered comparable average doses within
      the DIN EN ISO 11608-1:2000 limits at all dosage levels. The GL revealed a higher
      coefficient of variation (CV) at 5 U, and the WR and WD had higher CVs at all
      dosage levels compared with the CS and SS. Injection force was higher for the WR,
      WD, and GL compared with the CS and SS at both dose speeds. In contrast to the CS
      and SS with an end-of-content feature, doses exceeding the remaining insulin
      could be dialed with the WR, GL, and WD and, apparently, dispensed with the WD.
      CONCLUSIONS: All pens fulfilled the dose accuracy requirements defined by DIN EN
      ISO 11608-1:2000 standards at all three dosage levels, with the WR, WD, and GL
      showing higher dosage variability and injection force compared with the SS and
      CS. Thus, the devices that deliver insulin glargine copies show different
      performance characteristics compared with the originator.

PMID- 24124964
TI  - Different injection frequencies of basal insulins in type 2 diabetes patients
      under real-life conditions: a retrospective database analysis.
AB  - AIMS: Little is known about routine use of basal insulins [glargine, detemir,
      neutral protamine Hagedorn (NPH)] in primary care patients with type 2 diabetes.
      The aim was to compare injection frequencies of basal insulins in type 2 diabetes
      in primary care practices, both for basal-supported oral therapy (BOT) and basal
      bolus treatment [intensified conventional therapy (ICT)] regimens. METHODS:
      Primary care data from 4211 glargine (BOT/ICT, 2247/1964), 1290 detemir
      (490/800), and 3876 NPH (1331/2425) insulin users were retrospectively analyzed
      (Disease Analyzer database, May 2009-April 2012). Logistic regression (>1 daily
      injection) and propensity scores were used to adjust for various confounders
      (age, sex, type of physician, dosage, body mass index, glycosylated hemoglobin).
      RESULTS: Overall, >1 daily injections were observed in 7.5% of glargine users
      (BOT, 6.2%; ICT, 9.0%), which was lower than for detemir (overall, 25.4%; BOT,
      22.0%; ICT, 27.4%) and NPH (25.4%; BOT, 23.9%; ICT, 27.2%) insulin (all p <
      .001). The adjusted odds of having >1 injection was lower for glargine compared
      with detemir (odds ratio, 0.26; 95% CI 0.22-0.32) and NPH-insulin (0.20; 0.17
      0.23). Similar results were found for BOT or ICT and after propensity score
      matching. CONCLUSIONS: Glargine is associated with significantly lower injection
      frequencies than other basal insulins. These findings might impact patient
      reported outcomes, quality of life, treatment satisfaction, and economic aspects
      of diabetes treatment.

PMID- 24124965
TI  - The artificial pancreas: is it important to understand how the beta cell controls
      blood glucose?
AB  - It has been more than 7 years since the first fully automated closed-loop insulin
      delivery system that linked subcutaneous insulin delivery and glucose sensing was
      published. Since the initial report, the physiologic insulin delivery (PID)
      algorithm used to emulate the beta cell has been modified from the original
      proportional-integral-derivative terms needed to fit the beta cell's biphasic
      response to a hyperglycemic clamp to include terms emulating cephalic phase
      insulin release and the effect of insulin per se to inhibit insulin secretion. In
      this article, we compare the closed-loop glucose profiles obtained as each new
      term has been added, reassess the ability of the revised PID model to describe
      the beta cells' insulin response to a hyperglycemic clamp, and look for the first
      time at its ability to describe the response to a hypoglycemic clamp. We also
      consider changes that might be added to the model based on perfused pancreas
      data. We conclude that the changes introduced in the PID model have
      systematically improved the closed-loop meal response. We note that the changes
      made do not adversely affect the ability of the model to fit hyperglycemic clamp
      data but are necessary to fit the response to a hypoglycemic clamp. Finally, we
      note a number of beta cell characteristics observed in the perfused pancreas have
      not been included in the model. We suggest that continuing the effort to
      understand and incorporate aspects of how the beta cell achieves glucose control
      can provide valuable insights into how improvements in future artificial pancreas
      algorithms might be achieved. 

PMID- 24124966
TI  - Average daily risk range as a measure for clinical research and routine care.
AB  - There is emerging evidence suggesting that glycemic variability may relate to
      risk for diabetes-related complications. This article provides a description of
      average daily risk range (ADRR), a diabetes-specific measure of risk for
      hyperglycemia and hypoglycemia, and provides a summary of research using ADRR and
      clinical applications of ADRR. Average daily risk range is a variability metric
      that is based on "risk" values obtained from glucose levels that are
      mathematically transformed to give equal weight to hyperglycemic and hypoglycemic
      excursions. It can be calculated using self-monitoring of blood glucose or
      continuous glucose monitoring (CGM) data. The ADRR is scored based on risk
      categories: low risk, 0-19; moderate risk, 20-40; and high risk, 40 and above.
      Research using ADRR has found it to be a reliable predictor of extreme blood
      glucose values regardless of diabetes type and patients' age. Moreover, in
      treatment studies, ADRR presents as a very conservative measure of variability.
      Clinically, ADRR can provide meaningful data related to patients' risk for
      hyperglycemia and hypoglycemia that is not available from glycated hemoglobin
      values. Average daily risk range scores may also help clinicians to identify
      patients who may be overtreating blood glucose levels, leading to very high or
      low values. To expand the utility of ADRR, future research should examine the
      validity of existing risk cutoff scores for pediatric patients, determine if ADRR
      cutoff scores need to be modified for CGM data, and investigate whether patients'
      ADRR scores also relate to the development of long-term complications, including
      retinopathy and microalbuminuria. 

PMID- 24124968
TI  - A new test strip technology platform for self-monitoring of blood glucose.
AB  - In the management of diabetes, accuracy of devices used for self-monitoring of
      blood glucose (SMBG) is critical because SMBG results can affect patient diabetes
      related health outcomes. A new blood glucose monitoring system (BGMS) platform
      has been developed that is based on the new CONTOUR(r) NEXT (CN) test strip. This
      BGMS platform uses a proprietary electron mediator and algorithm to minimize
      errors at different steps in the testing process, thus minimizing outliers and
      significantly improving accuracy from prior-generation blood glucose meter
      systems. As demonstrated by questionnaire results from clinical studies with the
      new BGMS platform, accuracy and ease of use are important considerations for
      people with diabetes and their health care professionals when selecting an SMBG
      device. This article provides an overview of laboratory studies and clinical
      trials in the hands of lay users involving the performance of the portfolio of
      blood glucose meters that uses the new test strip. Each BGMS in the platform,
      which includes the CONTOUR XT (CONTOUR NEXT EZ in the United States), CONTOUR
      NEXT LINK, CONTOUR NEXT USB, and CN systems, demonstrated advanced accuracy both
      in the laboratory and in the hands of subjects (people with diabetes) and trained
      health care professionals. All systems met and exceeded International
      Organization for Standardization accuracy criteria (both ISO 15197:2003 and ISO
      15197:2013). Each system in the new BGMS platform delivers advanced accuracy,
      which is essential to people who utilize SMBG for improved management. 

PMID- 24124967
TI  - Role of health information technologies in the Patient-centered Medical Home.
AB  - A national effort to reform primary care, known as the Patient-Centered Medical
      Home (PCMH), requires fulfillment of six standards determined by the National
      Committee for Quality Assurance to (1) enhance access and continuity, (2)
      identify and manage patient populations, (3) plan and manage care, (4) provide
      self-care and community support, (5) track and coordinate care, and (6) measure
      and improve performance. Information technologies play a vital role in the
      support of most, if not all, of these standards. However, given the newness of
      the PCMH, little is known on how health information technologies (HITs) have been
      employed to accomplish these objectives. This article will review the role of
      HITs, including electronic health records, web-based patient portals,
      telemedicine, and patient registries, with a focus on diabetes care, and how
      these technologies have been engaged in the establishment of the PCMH. In
      addition, we will discuss the benefits and potential risks and barriers to
      employing these technologies, including privacy and security concerns, as well as
      describe next steps for future work in this important area. 

PMID- 24124969
TI  - The new glucose standard POCT12-A3 misses the mark.
AB  - POCT12-A3 is a Clinical Laboratory Standards Institute standard for hospitals
      about hospital glucose meter procedures and performance standards. I have
      reviewed this standard based on the attributes of an ideal performance standard.
      POCT12-A3 has tighter limits than its predecessor for 95% of results, the limits
      widen for 98% of results, and there are no limits for 2% of results. It is hard
      to fathom that 2% of the results are unspecified and could cause life-threatening
      results, as glucose meters do not perform this poorly. There should be a
      specification for unreported results since, by definition, point-of-care-testing
      assays are time sensitive. POCT12-A3 provides useful advice about the glucose
      testing procedure but provides evaluation guidance only about analytical
      performance. Moreover, the recommended protocol to assess meter performance is
      biased and likely to underestimate the observed performance. The guideline would
      be improved if its specification were based on an error grid and contained
      evaluation protocols for user errors. 

PMID- 24124970
TI  - Diabetes technology, innovation, and the U.S. health insurance system.
AB  - The flow of funds in the U.S. health care system is crucial both for the
      provision of services to patients and to encourage innovation that enables long
      term improvement of health services. Rising concern about health care costs often
      includes concerns about inappropriate adoption of costly or unnecessary
      technology. Many innovations in diabetes technology may involve personal
      technology, which does not qualify under existing health insurance categories
      such as "durable medical equipment" or under a currently defined telehealth
      technology. In such cases, the diabetes technology industry may be developing
      types of technology that are so innovative they do not have clearly established
      payment mechanisms in the existing U.S. fee for service health care reimbursement
      system. This article describes key features of the U.S. health care payment
      system relevant to developers of new diabetes technologies. 

PMID- 24124971
TI  - Analytical performance and clinical use of a hemoglobin A1c point-of-care
      analyzer in a pediatric unit.

PMID- 24124973
TI  - Travel-acquired subcutaneous Sparganum proliferum infection diagnosed by
      molecular methods.

PMID- 24124974
TI  - Predicting falls using two instruments (the Hendrich Fall Risk Model and the
      Morse Fall Scale) in an acute care setting in Lebanon.
AB  - AIMS AND OBJECTIVES: To assess the predictive value of two instruments (the Morse
      Fall Scale (MFS) and the Heindrich II Fall Risk Model (HFRM)] in a Middle Eastern
      country (Lebanon) and to evaluate the factors that are related to falls. DESIGN:
      A prospective observational cross-sectional design was used. BACKGROUND: Falls
      and fall-related injuries in the acute care settings contribute a substantial
      health and economic burden on patients and organisations. Preventing falls is a
      priority for most healthcare organisations. While the risk of falling cannot be
      eliminated, it can be significantly reduced through accurate assessment of
      patients' risk of falling. METHODS: Data from 1815 inpatients at the American
      University of Beirut Medical Center (AUBMC) in Lebanon were evaluated using two
      instruments to predict falls: the MFS and the HFRM. RESULTS: The incidence of
      falls was 2.7% in one year. The results indicate that while the instruments were
      significantly correlated, the HFRM was more sensitive in predicting falls than
      the MFS. The internal consistency of both scales was moderate, but inter-rater
      reliability was high. Patients using antiepileptic drugs and assistance devises
      had higher odds of falling. CONCLUSIONS: Although both instruments were easy to
      use in a Middle Eastern country, the HFRM rather than the MFS is recommended for
      inpatients in an acute care setting as it had higher sensitivity and specificity.
      RELEVANCE TO CLINICAL PRACTICE: It is recommended that while the HFRM had
      adequate sensitivity, it is not seamless, and as such, nurses should not rely
      entirely on it. Rather, nurses should use their expert clinical judgement, their
      ethical obligations and cultural considerations to implement a safer environment
      of care for the patient.

PMID- 24124975
TI  - Superiority of acetate compared with lactate in a rodent model of severe
      hemorrhagic shock.
AB  - BACKGROUND: Recently, we have shown that the use of lactated Ringer's (LR)
      solution is inferior to pure Ringer's solution (RS) in treatment of severe
      hemorrhagic shock in rats. The present study was performed to evaluate whether
      this is a specific effect of lactate or also applies to another metabolizable
      anion, namely acetate. MATERIAL AND METHODS: We subjected male Wistar rats to
      hemorrhagic shock by dropping the mean arterial blood pressure to 25-30 mm Hg for
      60 min, resuscitated with acetated Ringer's (AR) solution, LR solution, RS, or
      normal saline (NS) within 30 min, and further observed the animals for 180 min.
      RESULTS: Administration of AR solution prolonged median survival to 115 min
      compared with 50 min for resuscitation with LR solution or 85 and 90 min for NS
      and RS, respectively. Resuscitation with AR solution and LR solution clearly
      improved metabolic acidosis compared with NS and RS but tissue injury, indicated
      by plasma enzyme activities, was most pronounced in the LR solution group, medium
      in the NS and RS groups, and least in the AR solution group. CONCLUSIONS: In
      severe hemorrhagic shock, resuscitation with both RS and NS is superior to
      administration of LR solution but initial outcome is even further improved if AR
      solution is used. Mere amelioration of the acid-base status by AR solution may
      explain its superior role compared with RS and NS but cannot be responsible for
      its superiority compared with LR solution. Here, direct injury by lactate has to
      be discussed.

PMID- 24124976
TI  - Penehyclidine hydrochloride inhibits the release of high-mobility group box 1 in
      lipopolysaccharide-activated RAW264.7 cells and cecal ligation and puncture
      induced septic mice.
AB  - BACKGROUND: High-mobility group box 1 (HMGB1) is a critical mediator in the
      pathogenesis of many inflammatory diseases. Penehyclidine hydrochloride (PHC) has
      been proven to reduce sepsis-related mortality and sepsis-induced pathological
      complications. These effects are because of the reduced expression and release of
      many inflammatory mediators, although it is not clear whether PHC affects the
      expression and release of HMGB1. In this study, we explored the effect of PHC on
      the release of HMGB1 in lipopolysaccharide (LPS)-activated RAW264.7 cells and
      cecal ligation and puncture (CLP)-induced septic mice. MATERIALS AND METHODS:
      RAW264.7 cells were incubated with LPS in the presence or absence of various
      concentrations of PHC. The expression levels of HMGB1 in the culture supernatant
      were detected by enzyme-linked immunosorbent assay and real-time polymerase chain
      reaction. Western blotting was used to observe changes in the translocation of
      HMGB1 from the nucleus to the cytoplasm, and the nuclear factor (NF)-kappaB
      activity in the nuclear extract was detected by the NF-kappaB p50/p65
      Transcription Factor Assay Kit. In addition, 48 CLP-induced septic BALB/c were
      treated with different concentrations of PHC 1 h before performing the CLP, and
      the level of serum HMGB1 and the functional parameters of multiple organs were
      determined using several detection kits. RESULTS: We found that PHC inhibited the
      release of HMGB1 in LPS-activated RAW264.7 cells and CLP-induced septic mice. PHC
      inhibited the translocation of HMGB1 from the nucleus to the cytoplasm and also
      suppressed the expression of HMGB1 messenger RNA. Furthermore, PHC inhibited the
      translocation of NF-kappaB from the cytoplasm to the nucleus in LPS-activated
      RAW264.7 cells in a dose-dependent manner. Compared with the CLP alone group, the
      levels of alanine aminotransferase, aspartate aminotransferase, blood urea
      nitrogen, creatinine, and creatine kinase were significantly decreased in mice
      treated with 0.45 mg/kg of PHC (P < 0.01). CONCLUSIONS: Our study demonstrates
      that PHC inhibits the translocation of HMGB1 from the nucleus to the cytoplasm
      and the expression of HMGB1 messenger RNA in a dose-dependent manner. The
      mechanism responsible for these effects involves the NF-kappaB signaling pathway.
      Moreover, PHC can significantly protect important organs, such as the liver,
      kidney, and heart in mice with sepsis.

PMID- 24124977
TI  - Aberrant expression of laminin gamma2 correlates with poor prognosis and promotes
      invasion in extrahepatic cholangiocarcinoma.
AB  - BACKGROUND: To investigate the potential role of laminin gamma2 and its
      correlation with prognosis in patients with extrahepatic cholangiocarcinoma
      (CCA). MATERIALS AND METHODS: Laminin gamma2 expression was evaluated by
      immunohistochemistry in 72 extrahepatic CCA patients after surgical resection.
      Knockdown of laminin gamma2 was achieved via small interfering RNA transfection
      in the extrahepatic CCA cell line QBC939. RESULTS: Thirty-six of 72 extrahepatic
      CCAs (50%) stained positive for laminin gamma2 in two types of patterns: stromal
      staining (28/72, 39%) and cytoplasmic staining (24/72, 33%). All 16 paracancerous
      tissue samples showed negative staining. Both stromal and cytoplasmic laminin
      gamma2 expressions correlated with lymph node metastasis. Kaplan-Meier analysis
      showed that aberrant expression of laminin gamma2 correlated with poor overall
      survival and early recurrence. Cox regression analysis further demonstrated that
      laminin gamma2 expression was a significant independent predictor of poor overall
      survival and early recurrence. Immunofluorescence staining revealed cytoplasmic
      expression of laminin gamma2 in QBC939 cells. Knockdown of laminin gamma2
      significantly reduced QBC939 cell invasion and migration. CONCLUSIONS: Aberrant
      expression of laminin gamma2 correlates with poor prognosis and promotes invasion
      in extrahepatic CCA.

PMID- 24124978
TI  - Lack of association between LIPC-514 C/T polymorphism of hepatic lipase and
      endometriosis in Iranian women.
AB  - AIM: Patients with endometriosis may suffer from dyslipidemia. Hepatic lipase
      (HL) is involved in the metabolism of lipoproteins and has an important role in
      reverse cholesterol transport. The aim of this study was to investigate the
      association between the LIPC-514 C/T polymorphism in the HL gene and the risk of
      endometriosis in a group of Iranian women. METHODS: Ninety-seven patients with
      endometriosis and 107 women who were negative for endometriosis after diagnostic
      laparoscopy, as control group, were enrolled in this cross-sectional study.
      Samples were analyzed for polymorphism of the HL gene using polymerase chain
      reaction restriction fragment length polymorphism. RESULTS: Multivariate analysis
      was used to examine the association between the risk of endometriosis and LIPC
      514 C/T polymorphism. There was no statistically significant difference in the
      frequency of the LIPC-514 C/T polymorphism between patients and the controls
      (60.7% CC, 34.6% CT, 4.7% TT versus 68.4%, 27.4%, 4.2%, respectively, P = 0.52).
      CONCLUSION: The present study suggested that the LIPC-514 C/T polymorphism of the
      HL gene has no significant association with the risk of endometriosis in the
      studied Iranian women.

PMID- 24124979
TI  - A zwitterionic carbanion frustrated by boranes--dihydrogen cleavage with weak
      Lewis acids via an "inverse" frustrated Lewis pair approach.
AB  - The synthesis, structural characterization, and acid-base chemistry of
      [C(SiMe2OCH2CH2OMe)3]Na (2), a sterically encumbered zwitterionic organosodium
      compound, is reported. 2 is a strong Bronsted base that forms frustrated Lewis
      pairs (FLPs) with a number of boron-containing Lewis acids ranging from weakly
      Lewis acidic aryl and alkyl boranes to various alkyl borates. These
      intermolecular FLPs readily cleave H2, which confirms that even poor Lewis acids
      can engage in FLP-mediated H2 cleavage provided that the present bulky base is of
      sufficiently high Bronsted basicity. 

PMID- 24124980
TI  - The possibility and implications of dynamic nanoparticle surfaces.
AB  - Understanding the precise nature of a surface or interface is a key component
      toward optimizing the desired properties and function of a material. For
      semiconductor nanocrystals, the surface has been shown to modulate fluorescence
      efficiency, lifetime, and intermittency. The theoretical picture of a nanocrystal
      surface has included the existence of an undefined mixture of trap states that
      arise from incomplete passivation. However, our recent scanning transmission
      electron microscope movies and supporting theoretical evidence suggest that,
      under excitation, the surface is fluctuating, creating a dynamic population of
      surface and subsurface states. This possibility challenges our fundamental
      understanding of the surface and could have far-reaching ramifications for
      nanoparticle-based technologies. In this Perspective, we discuss the current
      theories behind the optical properties of nanocrystals in the context of
      fluxionality. 

PMID- 24124981
TI  - AtFKBP16-1, a chloroplast lumenal immunophilin, mediates response to
      photosynthetic stress by regulating PsaL stability.
AB  - Arabidopsis contains 16 putative chloroplast lumen-targeted immunophilins (IMMs).
      Proteomic analysis has enabled the subcellular localization of IMMs
      experimentally, but the exact biological and physiological roles of most luminal
      IMMs remain to be discovered. FK506-binding protein (FKBP) 16-1, one of the
      lumenal IMMs containing poorly conserved amino acid residues for peptidyl-prolyl
      isomerase (PPIase) activity, was shown to play a possible role in chloroplast
      biogenesis in Arabidopsis, and was also found to interact with PsaL in wheat. In
      this study, further evidence is provided for the notion that Arabidopsis FKBP16-1
      (AtFKBP16-1) is transcriptionally and post-transcriptionally regulated by
      environmental stresses including high light (HL) intensity, and that
      overexpression of AtFKBP16-1 plants exhibited increased photosynthetic stress
      tolerance. A blue native-polyacrylamide gel electrophoresis/two-dimensional (BN
      PAGE/2-D) analysis revealed that the increase of AtFKBP16-1 affected the levels
      of photosystem I (PSI)-light harvesting complex I (LHCI) and PSI-LHCI-light
      harvesting complex II (LHCII) supercomplex, and consequently enhanced tolerance
      under conditions of HL stress. In addition, plants overexpressing AtFKBP16-1
      showed increased accumulation of PsaL protein and enhanced drought tolerance.
      Using a protease protection assay, AtFKBP16-1 protein was found to have a role in
      PsaL stability. The AtPsaL levels also responded to abiotic stresses derived from
      drought, and from methyl viologen stresses in wild-type plants. Taken together,
      these results suggest that AtFKBP16-1 plays a role in the acclimation of plants
      under photosynthetic stress conditions, probably by regulating PsaL stability. 

PMID- 24124982
TI  - Self-assessed mental health problems and work capacity as determinants of return
      to work: a prospective general population-based study of individuals with all
      cause sickness absence.
AB  - BACKGROUND: Mental health problems are common in the work force and influence
      work capacity and sickness absence. The aim was to examine self-assessed mental
      health problems and work capacity as determinants of time until return to work
      (RTW). METHODS: Employed women and men (n=6140), aged 19-64 years, registered as
      sick with all-cause sickness absence between February 18 and April 15, 2008
      received a self-administered questionnaire covering health and work situation
      (response rate 54%). Demographic data was collected from official registers. This
      follow-up study included 2502 individuals. Of these, 1082 were currently off sick
      when answering the questionnaire. Register data on total number of benefit
      compensated sick-leave days in the end of 2008 were used to determine the time
      until RTW. Self-reported persistent mental illness, the WHO (Ten) Mental Well
      Being Index and self-assessed work capacity in relation to knowledge, mental,
      collaborative and physical demands at work were used as determinants. Multinomial
      and binary logistic regression analyses were used to estimate odds ratios with
      95% confidence intervals (CI) for the likelihood of RTW. RESULTS: The likelihood
      of RTW (>= 105 days) was higher among those with persistent mental illness OR=
      2.97 (95% CI, 2.10-4.20) and those with low mental well-being OR= 2.89 (95% CI,
      2.31-3.62) after adjusting for gender, age, SES, hours worked and sick leave
      2007. An analysis of employees who were off sick when they answered the
      questionnaire, the likelihood of RTW (>= 105 days) was higher among those who
      reported low capacity to work in relation to knowledge, mental, collaborative and
      physical demands at work. In a multivariable analysis, the likelihood of RTW (>=
      105 days) among those with low mental well-being remained significant OR=1.93
      (95% CI 1.46-2.55) even after adjustment for all dimensions of capacity to work.
      CONCLUSION: Self-assessed persistent mental illness, low mental well-being and
      low work capacity increased the likelihood of prolonged RTW. This study is unique
      because it is based on new sick-leave spells and is the first to show that low
      mental well-being was a strong determinant of RTW even after adjustment for work
      capacity. Our findings support the importance of identifying individuals with low
      mental well-being as a way to promote RTW.

PMID- 24124985
TI  - Visualisation for increasing health intentions: enhanced effects following a
      health message and when using a first-person perspective.
AB  - The present research explored whether visualising engaging in a health behaviour
      resulted in increased intentions to engage in that behaviour, when combined with
      an informational health message. Further, the effects of the visual perspective
      (first-person vs. third-person) used to visualise the health behaviour were
      explored. In an online questionnaire study employing a 2 * 3 between-participants
      experimental design, participants (N = 532) read vs. did not read an
      informational health message about the benefits of increasing fruit consumption,
      then visualised (from first-person vs. third-person perspective) vs. did not
      visualise themselves increasing their fruit consumption. Intentions to increase
      fruit consumption were assessed, as were potential mediating variables. The
      results indicated that visualisation (irrespective of perspective) did not result
      in increased intentions when it was not combined with the health message.
      However, when participants had read the health message, visualisation resulted in
      significantly stronger intentions, and the first-person perspective was
      significantly more effective than the third-person perspective. The beneficial
      effect of visualisation, and the first-person perspective, on intentions was
      mediated by increased self-efficacy and action planning. Findings are discussed
      in relation to existing research on visualisation and perspective, and in terms
      of practical applications for health promotion efforts.

PMID- 24124986
TI  - Integrating cognitive process and descriptive models of attitudes and
      preferences.
AB  - Discrete choice experiments--selecting the best and/or worst from a set of
      options--are increasingly used to provide more efficient and valid measurement of
      attitudes or preferences than conventional methods such as Likert scales.
      Discrete choice data have traditionally been analyzed with random utility models
      that have good measurement properties but provide limited insight into cognitive
      processes. We extend a well-established cognitive model, which has successfully
      explained both choices and response times for simple decision tasks, to complex,
      multi-attribute discrete choice data. The fits, and parameters, of the extended
      model for two sets of choice data (involving patient preferences for dermatology
      appointments, and consumer attitudes toward mobile phones) agree with those of
      standard choice models. The extended model also accounts for choice and response
      time data in a perceptual judgment task designed in a manner analogous to best
      worst discrete choice experiments. We conclude that several research fields might
      benefit from discrete choice experiments, and that the particular accumulator
      based models of decision making used in response time research can also provide
      process-level instantiations for random utility models.

PMID- 24124987
TI  - A resonant scanning dipole-antenna probe for enhanced nanoscale imaging.
AB  - We present a scanning antenna probe that provides 35 nm optical hotspots with a
      16-fold excitation enhancement. A resonant optical antenna, tuned to operation in
      the visible, is carved into the aluminum-coated scanning probe. The antenna
      resonances, field localization, excitation, and polarization response are probed
      in the near-field by scanning over single fluorescent nanobeads. At the same
      time, the distance-dependent coupling of the emission to the antenna mode is
      mapped. Good agreement with theory is obtained. The presented scanning antenna
      approach is useful for both nanoscale plasmonic mode imaging and (bio)imaging. 

PMID- 24124988
TI  - Sociodemographic and sexual behavior characteristics of an online MSM sample in
      Guangdong, China.
AB  - Public health research and interventions often assume that men who have sex with
      men (MSM) who use the Internet in China have similar characteristics to those in
      Western countries, though with little empirical evidence. This study aimed to
      describe and examine the sociodemographic and basic sexual behavioral
      characteristics of an online sample of MSM in Guangdong, China. In 2010, a total
      of 1100 MSM were recruited from an lesbian, gay, bisexual, and transgender (LGBT)
      oriented website and were asked about their sociodemographic and sexual behavior
      characteristics. The majority of the participants (77.9%) self-identified as
      homosexual, and the mean age was 30.0 years (SD = 6.7). About 80% of the
      participants had attained a college degree and only 4.8% were unemployed. About
      60% had a monthly salary of more than CNY 3000 (476 USD), and more than 10% were
      married. The majority (71.7%) had used condoms in the last anal sex. Nearly half
      of the participants have never been tested for HIV or other sexually transmitted
      infections (STIs) (47.3% and 47.7%, respectively). More than 80% were willing to
      be contacted by researchers after the survey. Findings indicate that the
      sociodemographic characteristics of Chinese MSM who use the Internet are
      relatively similar to those in the Western countries. However, Chinese MSM are
      less likely to self-identify as homosexual and be tested for HIV and other STIs
      than Western MSM. On a positive note, Chinese MSM would be likely to engage in e
      technology research showing potential feasibility of an online HIV/STI
      intervention. 

PMID- 24124989
TI  - A frequency questionnaire to estimate free-living physical activity among
      Tunisian preadolescent and adolescent children.
AB  - OBJECTIVE: To develop a child- and adolescent-appropriate physical activity
      frequency questionnaire (PAFQ) in Tunisia, North Africa. DESIGN: A PAFQ was
      developed from a physical activity (PA) inventory that comprised major activity
      components (at home, preparing meals, school time, transport, non-sport leisure,
      sports, prayer and sleeping time). Then, type and duration of each activity
      undertaken during the past week were estimated. Total energy expenditure (TEE)
      estimated by the PAFQ was compared with data derived from two criterion methods:
      heart-rate monitoring (HRM) and a 24 h PA recall (24h-R), both collected during a
      3 d period including one weekday and two weekend days. SETTING: Two elementary
      schools and two high schools of the most developed and urbanized area, Greater
      Tunis. SUBJECTS: One hundred and forty-two volunteer children and adolescents
      aged 10-19 years. RESULTS: The PAFQ strongly was correlated with both HRM (r =
      0.70; 95% CI 0.62, 0.76) and 24h-R (r = 0.81; 95% CI 0.77, 0.84). It featured
      acceptable agreement with both criterion measures, slightly underestimating TEE
      compared with 24h-R (-2.8%, mean of individual differences -272.7 kJ/d; 95% CI 
      490.6, -57.4 kJ/d) and moderately overestimating it compared with HRM (+11.3%,
      mean of individual differences +1106.2 kJ/d; 95% CI 845.8, 1366.6 kJ/d).
      Reliability ranged from moderate to good (weighted kappa coefficients from 0.47
      to 0.78 and intra-class correlation coefficients between 0.79 and 0.86 for energy
      expenditure by PA categories), indicating strong agreement between the two
      assessments. CONCLUSIONS: This PAFQ could be useful in the description and
      surveillance of PA patterns or for the evaluation of population-based
      interventions directed at promoting PA in Tunisian children and adolescents.

PMID- 24124990
TI  - Identification of novel leads applying in silico studies for Mycobacterium
      multidrug resistant (MMR) protein.
AB  - Multidrug efflux mechanism is the main cause of intrinsic drug resistance in
      bacteria. Mycobacterium multidrug resistant (MMR) protein belongs to small
      multidrug resistant family proteins (SMR), causing multidrug resistance to proton
      (H(+))-linked lipophilic cationic drug efflux across the cell membrane. In the
      present work, MMR is treated as a novel target to identify new molecular entities
      as inhibitors for drug resistance in Mycobacterium tuberculosis. In silico
      techniques are applied to evaluate the 3D structure of MMR protein. The putative
      amino acid residues present in the active site of MMR protein are predicted.
      Protein-ligand interactions are studied by docking cationic ligands transported
      by MMR protein. Virtual screening is carried out with an in-house library of
      small molecules against the grid created at the predicted active site residues in
      the MMR protein. Absorption distribution metabolism and elimination (ADME)
      properties of the molecules with best docking scores are predicted. The studies
      with cationic ligands and those of virtual screening are analysed for
      identification of new lead molecules as inhibitors for drug resistance caused by
      the MMR protein. 

PMID- 24124992
TI  - Nanosheet-assembled NiO microstructures for high-performance supercapacitors.
AB  - Nanosheet-assembled NiO microstructures have been synthesized via a hydrothermal
      method. The presence of anionic surfactant in the fabrication process initiates
      the formation of lamellar micelles and a self-assembling process. This leads to
      the formation of NiO nanosheets and organizes it into microstructures. The effect
      of preparation temperature on the morphological, structural, and electrochemical
      properties and stability upon continuous charge/discharge cycles has been
      examined for supercapacitor applications. Electrochemical analysis demonstrated
      that NiO nanosheets prepared at 160  degrees C are capable of delivering a
      specific capacitance of 989 F g(-1) at a scan rate of 3 mV s(-1) for the
      potential window of 0-0.6 V. The nanosheets exhibit excellent capacity retention,
      97% retention after 1000 continuous charge/discharge cycles, and an energy
      density of 49.45 W h kg(-1). 

PMID- 24124993
TI  - Enhancing activities of daily living of chronic stroke patients in primary health
      care by modified constraint-induced movement therapy (HOMECIMT): study protocol
      for a cluster randomized controlled trial.
AB  - BACKGROUND: Stroke leads to constant rehabilitation needs even at the chronic
      stage. However, although many stroke patients receive physical or occupational
      therapy in primary health care, treatment prescriptions do not generally specify
      therapeutic goals; in particular, participation is not established as an explicit
      therapeutic goal in the ambulatory setting. The primary aim of this study is to
      evaluate the efficacy of a therapy regimen for chronic stroke patients (modified
      'constraint-induced movement therapy (CIMT) at home') with impaired hand or arm
      function with regard to the prerequisites of participation in everyday
      activities: a sufficient arm and hand function. 'CIMT at home' will be compared
      with conventional physical and occupational therapy ('therapy as usual').
      METHODS/DESIGN: The study is a parallel cluster randomized controlled trial with
      therapy practices as clusters (n = 48). After written consent from the patients
      (n = 144), the therapists will be randomly assigned to treat either the
      intervention or the control group. Blinded external assessors will evaluate the
      patients using standardized outcome measures before and after the intervention,
      and six months later. The two coprimary endpoint assessments of arm and hand
      function as prerequisites for participation (defined as equal involvement in
      activities of daily living) are the motor activity log (quality of arm and hand
      use) and the Wolf motor function test (arm and hand function). These assessments
      are made four weeks post-treatment and relativized to baseline performance.
      Changes in primary outcomes will be analyzed with mixed models, which consider
      the hierarchical structure of the data and will be adjusted to the baseline
      measurements and sex. The primary analysis will be the comparison of the two
      randomized groups, with respect to the adjusted averages for each of the two
      coprimary endpoints. To keep an overall significance level of 5%, the two
      endpoints will be tested at the significance level of 5% each in hierarchical
      order. DISCUSSION: A modification of the CIMT, feasible in the patients' homes
      (CIMT at home), appears to be a promising therapeutic approach in the ambulatory
      care of chronic stroke patients. With proven efficacy and practicality, a
      participation-oriented, stroke-specific treatment would be available in primary
      care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01343602.

PMID- 24124994
TI  - Post-aural ache: an unusual presentation of a metastatic temporal bone lesion
      from a primary adenocarcinoma of the lung.
AB  - OBJECTIVE: We report a rare case of temporal bone metastasis from a lung primary,
      presenting only as post-aural tenderness. CASE REPORT: A 57-year-old man
      presented to our out-patient department with left post-aural pain of four months'
      duration. Clinical examination revealed tenderness in the left post-aural region;
      the ear, nose and throat examination was otherwise unremarkable. Computed
      tomography and contrast-enhanced magnetic resonance imaging showed erosion of the
      left petrous temporal bone. Incisional biopsy was carried out. Histopathological
      and immunohistochemical analysis showed infiltrative metastatic adenocarcinoma of
      the lung. Further imaging with positron emission tomography confirmed increased
      uptake from the right lower lobe of the lung, suggesting the site of the primary
      lesion. The patient was treated with chemo-radiotherapy. CONCLUSION: Post-aural
      pain is a non-specific symptom, and, with normal clinical and audiometric test
      results, rare lesions such as the one presented could be easily missed. A
      thorough clinical examination must be performed to identify genuine signs, and
      appropriate imaging undertaken to exclude rare causes, such as this metastatic
      lesion of the temporal bone.

PMID- 24124995
TI  - Kinetics of presynaptic filament assembly in the presence of single-stranded DNA
      binding protein and recombination mediator protein.
AB  - Enzymes of the RecA/Rad51 family catalyze DNA strand exchange reactions that are
      important for homologous recombination and for the accurate repair of DNA double
      strand breaks. RecA/Rad51 recombinases are activated by their assembly into
      presynaptic filaments on single-stranded DNA (ssDNA), a process that is regulated
      by ssDNA binding protein (SSB) and mediator proteins. Mediator proteins stimulate
      strand exchange by accelerating the rate-limiting displacement of SSB from ssDNA
      by the incoming recombinase. The use of mediators is a highly conserved strategy
      in recombination, but the precise mechanism of mediator activity is unknown. In
      this study, the well-defined bacteriophage T4 recombination system (UvsX
      recombinase, Gp32 SSB, and UvsY mediator) is used to examine the kinetics of
      presynaptic filament assembly on native ssDNA in vitro. Results indicate that the
      ATP-dependent assembly of UvsX presynaptic filaments on Gp32-covered ssDNA is
      limited by a salt-sensitive nucleation step in the absence of mediator. Filament
      nucleation is selectively enhanced and rendered salt-resistant by mediator
      protein UvsY, which appears to stabilize a prenucleation complex. This mechanism
      potentially explains how UvsY promotes presynaptic filament assembly at
      physiologically relevant ionic strengths and Gp32 concentrations. Other data
      suggest that presynaptic filament assembly involves multiple nucleation events,
      resulting in many short UvsX-ssDNA filaments or clusters, which may be the
      relevant form for recombination in vivo. Together, these findings provide the
      first detailed kinetic model for presynaptic filament assembly involving all
      three major protein components (recombinase, mediator, and SSB) on native ssDNA. 

PMID- 24124996
TI  - Proton transfer in hydrogen-bonded network of phenol molecules: intracluster
      formation of water.
AB  - Electron ionization and time-of-flight mass spectrometry was used to investigate
      the phenol clusters (PhOH)n of different size from single molecule to large
      clusters: in coexpansion with He, the dimers n = 2 are mostly generated; in Ar,
      large species of n >= 10 also occur. Besides [(PhOH)n](+*) cluster ion series,
      hydrated phenol cluster ions [(PhOH)n.xH2O](+*) with up to x = 3 water molecules
      and dehydrated phenol clusters [(PhOH)n-H2O](+*) were observed. The hydrated
      phenol series exhibits minima and maxima that are interpreted as evidence for
      proton transfer between the hydrogen bonded cluster ions of cyclic structures.
      The proton transfer leads to a water generation within the clusters, and
      subsequent elimination of the diphenyl ether molecule(s) from the cluster yields
      the hydrated phenol cluster ions. Alternatively, a water molecule release yields
      a series of dehydrated phenols, among which the diphenyl ether ion [PhOPh](+*) (n
      = 2) constitutes the maximum. 

PMID- 24124997
TI  - Ionic liquids as floatation media for cryo-ultramicrotomy of soft polymeric
      materials.
AB  - Ionic liquids (ILs) and their mixtures with low molecular solvents present ideal
      properties for use as flotation liquids in cryo-ultramicrotomy. With control of T
      g and eta by co-solvent addition, flat, ultra-thin sections are reliably floated
      onto transmission electron microscopy grids even at temperatures as low as -100
      degrees C. Even more, the liquids and their mixtures are stable in the microtome
      trough for several hours because of low vapor pressure and low solidification
      temperature. Compared to established flotation media for soft polymer systems,
      the time and skill needed for cryo-ultramicrotomy are significantly reduced.
      Although just a handful of ILs are discussed and a good general choice
      identified, if different liquid characteristics are needed for a particular
      sample, thousands of additional ILs will perform similarly, giving this new
      approach enormous flexibility. 

PMID- 24125011
TI  - Scoping reviews in occupational therapy: the what, why, and how to.
AB  - BACKGROUND/AIM: Scoping reviews are a method of identifying, locating, analysing
      and summarising relevant empirical literature and research findings on a
      nominated topic. A description of scoping reviews is provided with examples that
      have been published in the occupational therapy and related literature and
      outline of the uses of scoping reviews for research and in evidence-based
      practice. METHODS: Recent occupational therapy literature was searched to
      identify occupational therapy-related scoping reviews published in the refereed
      literature and to identify the methodologies used and topics covered. RESULTS: A
      limited range of scoping reviews was located and a summary of their results is
      provided as examples of scoping reviews in the occupational therapy field.
      CONCLUSION: The scoping review methodology is an efficient and effective approach
      for locating, analysing, summarising and presenting available literature and
      research findings on a particular topic. In comparison to a systematic review, it
      does not have the same high level of rigour, however does provide a general
      overview of the literature using a structured methodology to ensure consistency.
      The methodology of scoping reviews is effective for researchers where there is
      limited high level evidence available about a topic that would be required by a
      systematic review and provides an efficient way of identifying previous research
      and current knowledge gaps. Although there has been some scoping reviews
      published, it is predicted that there will be an increase in the future when the
      use of scoping reviews in occupational therapy is more fully realised and
      operationalised.

PMID- 24125012
TI  - Individual experiences of an acceptance-based pain management programme: an
      interpretative phenomenological analysis.
AB  - Acceptance of pain has been found to play an important role in adjusting to
      chronic pain, and the evidence-base is growing with regards to the effectiveness
      of acceptance-based interventions such as acceptance and commitment therapy,
      mindfulness and contextual cognitive behavioural therapy within pain management
      settings. Despite the growing interest in such interventions, previous studies
      into acceptance-based pain management programmes (PMPs) are quantitative and the
      exact processes at work during such programmes remain unknown. This study aims to
      add to previous quantitative research in the area by qualitatively exploring
      individual experiences of attending an acceptance-based PMP and identifying the
      key constituents of the programme that participants felt facilitated change. Semi
      structured interviews (n = 6) were analysed using interpretative phenomenological
      analysis, and five themes emerged: I'm not alone, others understand my pain,
      Freedom from pain taking over, A new self - one with pain, Parts of the programme
      participants felt facilitated change and Exercise is possible. These findings are
      then considered in relation to past research and relevant constructs in the
      literature. Implications for future research and clinical practice are also
      discussed alongside participant reflections and suggested areas for improvement.

PMID- 24125013
TI  - Structural and dynamics analysis of matrix metalloproteinases MMP-2 complexed
      with chemically modified tetracyclines (CMTs).
AB  - Matrix metalloproteinases (MMPs) play a critical role in physiological processes
      and pathological conditions such tumor invasion and metastasis. In recent years,
      a number of MMP inhibitors have been proposed, including the chemically modified
      tetracyclines (CMTs), which have been evaluated in preclinical cancer models
      showing promising results. This work provides insights into the structure and
      dynamics of the MMP-2 catalytic domain complexed with seven CMT (CMT-n), based on
      the analysis of molecular dynamics trajectories in solution. The comparative
      analysis of various relevant molecular aspects of the different complexes of MMP
      2 and CMT-n derivatives was performed aiming to elucidate the effect of ligands
      on the enzyme structure. These include the radial distribution function of the
      water molecules around the catalytic zinc, the solvent accessible surface area
      for the inhibitors and the root-mean-square fluctuation for all amino acid
      residues. The results help to understand the differences in the binding modes of
      related compounds and, therefore, add to further design of novel tetracycline
      based inhibitors for MMP enzymes. 

PMID- 24125014
TI  - High-risk human papilloma virus management in pregnancy with cervical
      intraepithelial neoplasia during pregnancy and postpartum in China.
AB  - AIM: To investigate the relationship between cervical intraepithelial neoplasia
      (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and
      postpartum in China. METHODS: In this prospective case-control study, 168
      pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical
      biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect
      HR-HPV DNA load amounts and the tests were completed in 3-6 months after
      childbirth. RESULTS: During pregnancy: as the CIN grade increased, the HR-HPV
      infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in
      logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the
      CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000),
      while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially
      the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher
      than that of other grades. During pregnancy and 3-6 months postpartum : the
      amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6
      months postpartum with the same grade of CIN. CONCLUSION: The findings emphasize
      the importance of undergoing the HCII test 3-6 months postpartum. It should be
      noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after
      childbirth. Further treatments of pregnancy with CIN should be considered
      according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months
      after birth, but not according to the persistence of HR-HPV during pregnancy.

PMID- 24125015
TI  - The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but
      uninfected infants.
AB  - The aim of this study was to compare the neurodevelopment of HIV-infected (HI)
      infants in combination with antiretroviral therapy also known as HAART (highly
      active antiretroviral therapy) to HIV-exposed uninfected (HEU) infants. Twenty
      seven HIV infected and 29 HEU infants under the age of one year attending the
      Empilweni Clinic at Rahima Moosa Mother and Child Hospital were studied. HI
      infants were assessed prior to initiating HAART and then for six months whilst on
      HAART. Neurodevelopment was assessed using the Bayley Scales of Infant and
      Toddler Development, 3rd ed (Bayley III). The HI infants scored significantly
      lower when compared to HEU infants for motor and language development at
      baseline, three months and six months follow up. No significant improvement in
      language (p = 0.46) and motor function (p = 0.91) occurred over time; however,
      developmental scores did not decrease. Cognitive development in the HI group was
      significantly lower when compared to the HEU group at visit one (p = 0.003). By
      six months follow-up, there were no significant differences between the two
      groups for cognitive development (p = 0.18). This study suggests that HIV
      positive infants are delayed when compared to HEU infants. HAART may help to
      prevent further delay; however, it does not reverse the neurological damage
      already present. There is a need for therapists to be involved in pediatric HIV
      clinical services in order to provide early developmental screening as well as
      rehabilitative services to those children in need. 

PMID- 24125016
TI  - Bacterial vaginosis in the context of lichen sclerosus in a prepubertal girl.
AB  - Group A beta-hemolytic streptococcus cause most vulvovaginal infections seen in
      prepubertal girls. Bacterial vaginosis is a common cause of abnormal vaginal
      discharge in women of childbearing age but is rare in children. Data are
      insufficient to suggest that bacterial vaginosis is an exclusively sexually
      transmitted disease. We report a 10-year-old girl with no history or suspicion of
      sexual abuse who developed bacterial vaginosis in the context of a lichen
      sclerosus being treated with tacrolimus ointment. Secondary bacterial infection
      in lichen sclerosus is uncommon. We speculate that the immunosuppressive effect
      of topical tacrolimus could have triggered the infection. 

PMID- 24125017
TI  - Analysis of human embryonic stem cells with regulatable expression of the cell
      adhesion molecule l1 in regeneration after spinal cord injury.
AB  - Cell replacement therapy is one potential avenue for central nervous system (CNS)
      repair. However, transplanted stem cells may not contribute to long-term recovery
      of the damaged CNS unless they are engineered for functional advantage. To fine
      tune regenerative capabilities, we developed a human neural cell line expressing
      L1, a regeneration-conducive adhesion molecule, under the control of a
      doxycycline regulatable Tet-off promoter. Controlled expression of L1 is desired
      because overexpression after regenerative events may lead to adverse
      consequences. The regulated system was tested in several cell lines, where
      doxycycline completely eliminated green fluorescent protein or L1 expression by 3
      5 days in vitro. Increased colony formation as well as decreased proliferation
      were observed in H9NSCs without doxycycline (hL1-on). To test the role of L1 in
      vivo after acute compression spinal cord injury of immunosuppressed mice, quantum
      dot labeled hL1-on or hL1-off cells were injected at three sites: lesion;
      proximal; and caudal. Mice transplanted with hL1-on cells showed a better Basso
      Mouse Scale score, when compared to those with hL1-off cells. As compared to the
      hL1-off versus hL1-on cell transplanted mice 6 weeks post-transplantation,
      expression levels of L1, migration of transplanted cells, and immunoreactivity
      for tyrosine hydroxylase were higher, whereas expression of chondroitin sulfate
      proteoglycans was lower. Results indicate that L1 expression is regulatable in
      human stem cells by doxycycline in a nonviral engineering approach. Regulatable
      expression in a prospective nonleaky Tet-off system could hold promise for
      therapy, based on the multifunctional roles of L1, including neuronal migration
      and survival, neuritogenesis, myelination, and synaptic plasticity.

PMID- 24125019
TI  - Photoelectrochemical behavior of n-type Si(111) electrodes coated with a single
      layer of graphene.
AB  - The behavior of graphene-coated n-type Si(111) photoanodes was compared to the
      behavior of H-terminated n-type Si(111) photoanodes in contact with aqueous
      K3[Fe(CN)6]/K4[Fe(CN)6] as well as in contact with a series of outer-sphere, one
      electron redox couples in nonaqueous electrolytes. The n-Si/Graphene electrodes
      exhibited stable short-circuit photocurrent densities of over 10 mA cm(-2) for
      >1000 s of continuous operation in aqueous electrolytes, whereas n-Si-H
      electrodes yielded a nearly complete decay of the current density within ~100 s.
      The values of the open-circuit photovoltages and the flat-band potentials of the
      Si were a function of both the Fermi level of the graphene and the
      electrochemical potential of the electrolyte solution, indicating that the n
      Si/Graphene did not form a buried junction with respect to the solution contact.

PMID- 24125018
TI  - S0-State model of the oxygen-evolving complex of photosystem II.
AB  - The S0 -> S1 transition of the oxygen-evolving complex (OEC) of photosystem II is
      one of the least understood steps in the Kok cycle of water splitting. We
      introduce a quantum mechanics/molecular mechanics (QM/MM) model of the S0 state
      that is consistent with extended X-ray absorption fine structure spectroscopy and
      X-ray diffraction data. In conjunction with the QM/MM model of the S1 state, we
      address the proton-coupled electron-transfer (PCET) process that occurs during
      the S0 -> S1 transition, where oxidation of a Mn center and deprotonation of a MU
      oxo bridge lead to a significant rearrangement in the OEC. A hydrogen bonding
      network, linking the D1-D61 residue to a Mn-bound water molecule, is proposed to
      facilitate the PCET mechanism.

PMID- 24125020
TI  - Varicella zoster virus in the temporal artery of a patient with giant cell
      arteritis.
AB  - We recently detected varicella zoster virus (VZV) in the temporal arteries (TA)
      of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs
      were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen
      predominated in the arterial adventitia, but without medial necrosis and
      multinucleated giant cells. During our continuing search for VZV antigen in GCA
      negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as
      VZV DNA, in multiple regions (skip areas) of the TA spanning 350 MUm, as well as
      in skeletal muscle adjacent to the infected TA. Additional pathological analysis
      of sections adjacent to those containing viral antigen revealed inflammation
      involving the arterial media and abundant multinucleated giant cells
      characteristic of GCA. Detection of VZV in areas of the TA with pathological
      features of GCA warrants further correlative pathological-virological analysis of
      VZV in GCA.

PMID- 24125021
TI  - Stacking order dependent second harmonic generation and topological defects in h
      BN bilayers.
AB  - The ability to control the stacking structure in layered materials could provide
      an exciting approach to tuning their optical and electronic properties. Because
      of the lower symmetry of each constituent monolayer, hexagonal boron nitride (h
      BN) allows more structural variations in multiple layers than graphene; however,
      the structure-property relationships in this system remain largely unexplored.
      Here, we report a strong correlation between the interlayer stacking structures
      and optical and topological properties in chemically grown h-BN bilayers,
      measured mainly by using dark-field transmission electron microscopy (DF-TEM) and
      optical second harmonic generation (SHG) mapping. Our data show that there exist
      two distinct h-BN bilayer structures with different interlayer symmetries that
      give rise to a distinct difference in their SHG intensities. In particular, the
      SHG signal in h-BN bilayers is observed only for structures with broken inversion
      symmetry, with an intensity much larger than that of single layer h-BN. In
      addition, our DF-TEM data identify the formation of interlayer topological
      defects in h-BN bilayers, likely induced by local strain, whose properties are
      determined by the interlayer symmetry and the different interlayer potential
      landscapes. 

PMID- 24125022
TI  - Bile duct adenoma (hamartoma of peribiliary glands): Importance of an adequate
      diagnosis.

PMID- 24125023
TI  - Improving scanning electron microscope resolution for near planar samples through
      the use of image restoration.
AB  - A method is presented for determining the point spread function (PSF) of an
      electron beam in a scanning electron microscope for the examination of near
      planar samples. Once measured, PSFs can be used with two or more low-resolution
      images of a selected area to create a high-resolution reconstructed image of that
      area. As an example, a 4* improvement in resolution for images is demonstrated
      for a fine gold particle sample. Since thermionic source instruments have high
      beam currents associated with large probe sizes, use of this approach implies
      that high-resolution images can be produced rapidly if the probe diameter is less
      of a limiting factor. Additionally, very accurate determination of the PSFs can
      lead to a better understanding of instrument performance as exemplified by very
      accurate measurement of the beam shape and therefore the degree of astigmatism.

PMID- 24125024
TI  - Intravascular papillary endothelial hyperplasia: histomorphological and
      immunohistochemical features.
AB  - BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a benign
      intravascular process with features mimicking other benign and malignant vascular
      proliferations. IPEH lesions predominate in the head-neck region and the
      extremities. The characteristic histomorphological feature of IPEH is a papillary
      structure covered with hyperplastic endothelial cells within the vascular lumen.
      It is critical that this clinically benign lesion should not be mistaken for well
      differentiated vascular tumors. In addition to the characteristic histological
      features, other useful diagnostic features included the intra-luminal location of
      the lesion, an intimate association with the organizing thrombus, the absence of
      necrosis, cellular pleomorphism, and mitotic activity. In addition,
      immunohistochemistry may indicate the vascular origin and proliferative index. In
      this study, we evaluated histomorphological and immunohistochemical findings
      (CD31, CD34, FVIII, type IV collagen, SMA, MSA, CD105, and Ki-67 staining) of ten
      IPEH cases. METHODS: Ten IPEH cases were re-examined for a panel of
      histomorphological and immunohistochemical features. CD31, CD34, FVIII, Type IV
      collagen, SMA and MSA antibodies utilized for immunohistochemical analysis.The
      histomorphological and immunohistochemical findings were evaluated by two
      independent pathologists using light microscopy. RESULTS: All ten cases involved
      intraluminal lesions with characteristic features of IPEH. All ten cases (100%)
      were stained positive for CD31 and CD34. The degree of staining with FVIII, type
      IV collagen, SMA, and MSA was variable. CONCLUSION: In this series of specimens,
      CD31 and CD34 were the most sensitive markers indicating the vascular origin of
      the lesion. Staining for the other vascular markers (FVIII, type IV collagen, SMA
      and MSA) was variable. Different maturation degrees of lesions may account for
      the variation in immunohistochemical staining. Few previous investigations
      evaluated a wide range of antigen panels in IPEH sections. In our opinion, the
      evaluation of immune markers in a larger sample set will reveal new features in
      the maturity and developmental pathogenesis of vascular lesions and angiogenesis.
      IPEH is a benign lesion, which must be differentiated from malignant tumors such
      as angiosarcoma and Kaposi's sarcoma. Improved definition of IPEH lesions using
      immunohistochemical markers may enhance the ability to differentiate between
      various vascular lesions. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1381849312101856.

PMID- 24125025
TI  - Effect of the systematised critical pathway protocol on emptying failure as a
      secondary complication of radical hysterectomy due to uterine cervix cancer.
AB  - AIMS AND OBJECTIVES: To evaluate the usefulness of this pathway in managing
      postoperative emptying failure as a secondary complication of radical
      hysterectomy. BACKGROUND: Postoperative urological management after radical
      hysterectomy has not been effective. We designed and prospectively applied a
      critical pathway for effective postoperative urological management after radical
      hysterectomy, based on early catheter removal and application of clean
      intermittent catheterisation. DESIGN: Retrospective qualitative study. MATERIALS
      AND METHODS: Retrospective review of results from a database of patients who
      underwent radical hysterectomy and pelvic lymphadenectomy for the treatment of
      uterine cervical cancer from 2004-2008 and analysis of questionnaires from ward
      nurses (Appendix 1) who were directly involved in patient care for measuring the
      clinical effectiveness. RESULTS: Data from a total of 185 patients were analysed.
      Mean period of the indwelling catheter was 8.3 (SD 1.1), 13.0 (SD 1.1) and 13.1
      (SD 3.3) days in the critical pathway (CP), parallel control (PC) and historical
      control (HC) groups, respectively. Among CP, HC and PC groups, the overall
      hospital stays were 14.1 (SD 4.8), 20.2 (SD 10) and 18.2 (SD 8.8) days and the
      periods of time for the indwelling catheters were 8.31 (SD 1.1), 13.1 (SD 3.3)
      and 13.0 (SD 1.1) days, respectively. Significant differences in the overall
      hospital stay and the postoperative hospital stay were observed between CP group
      and the other groups. Analysis of the questionnaires showed that 67% of nurses
      agreed that the critical pathway was more effective than the previous management
      pathway system. CONCLUSIONS: Our results demonstrated that CP is an effective
      treatment modality for the management of postoperative emptying failure after
      radical hysterectomy. RELEVANCE TO CLINICAL PRACTICE: Our critical pathway may be
      applicable to postoperative urological management of radical pelvic surgeries. It
      may help patients in understanding their hospital course of treatment and
      encourage patients to participate in their postoperative care.

PMID- 24125026
TI  - Efficient identification of Malassezia yeasts by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS).
AB  - BACKGROUND: Infections caused by Malassezia yeasts are most likely
      underdiagnosed, because fatty acid supplementation is needed for growth. Rapid
      identification of Malassezia species is essential for appropriate treatment of
      Malassezia-related skin infections, fungaemia and nosocomial outbreaks in
      neonates, children and adults and can be life-saving for those patients. Ma
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS) has been reported to be a rapid and reliable diagnostic tool to identify
      clinically important yeasts, but so far no data have been reported on
      identification of Malassezia isolates with this technique. OBJECTIVES: To create
      an extensive database of main mass spectra (MSPs) that will allow quick
      identification of Malassezia species by MALDI-TOF MS. METHODS: An in-house
      library of 113 MSPs was created from 48 reference strains from the CBS-KNAW yeast
      collection. The in-house library was challenged with two test sets of Malassezia
      strains, namely 165 reference strains from the CBS collection and 338 isolates
      collected in Greece, Italy, Sweden and Thailand. RESULTS: MALDI-TOF MS allowed
      correct identification of all 14 Malassezia spp. MALDI-TOF MS results were
      concordant with those of sequence analyses of the internal transcribed spacers
      (ITS1/ITS2) and the D1/D2 domains of the large subunit of the ribosomal DNA.
      CONCLUSIONS: Implementation of the MALDI-TOF MS system as a routine
      identification tool will contribute to correct identification of Malassezia
      yeasts with minimal effort and in a short turnaround time, which is especially
      important for the rapid identification of Malassezia in skin diseases and
      nosocomial outbreaks.

PMID- 24125027
TI  - Collaborative care for patients with depression and diabetes mellitus: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Diabetic patients with depression are often inadequately treated
      within primary care. These comorbid conditions are associated with poor outcomes.
      The aim of this systematic review was to examine whether collaborative care can
      improve depression and diabetes outcomes in patients with both depression and
      diabetes. METHODS: Medline, Embase, Cochrane library and PsyINFO were
      systematically searched to identify relevant publications. All randomized
      controlled trials of collaborative care for diabetic patients with depression of
      all ages who were reported by depression treatment response, depression
      remission, hemoglobin A1c (HbA1c) values, adherence to antidepressant medication
      and/or oral hypoglycemic agent were included. Two authors independently screened
      search results and extracted data from eligible studies. Dichotomous and
      continuous measures of outcomes were combined using risk ratios (RRs) and mean
      differences (MDs) with 95% confidence intervals (CIs) either by fixed or random
      effects models. RESULTS: Eight studies containing 2,238 patients met the
      inclusion criteria. Collaborative care showed a significant improvement in
      depression treatment response (RR = 1.33, 95% CI = 1.05-1.68), depression
      remission (adjusted RR = 1.53, 95% CI =1.11-2.12), higher rates of adherence to
      antidepressant medication (RR = 1.79, 95% CI = 1.19-2.69) and oral hypoglycemic
      agent (RR = 2.18, 95% CI = 1.61-2.96), but indicated a non-significant reduction
      in HbA1c values (MD = -0.13, 95% CI = -0.46-0.19). CONCLUSIONS: Improving
      depression care in diabetic patients is very necessary and important. Comparing
      with usual care, collaborative care was associated with significantly better
      depressive outcomes and adherence in patients with depression and diabetes. These
      findings emphasize the implications for collaborative care of diabetic patients
      with depression in the future.

PMID- 24125028
TI  - Impact of negative cognitions about body image on inflammatory status in relation
      to health.
AB  - OBJECTIVE: Evidence suggests that body dissatisfaction may relate to biological
      processes and that negative cognitions can influence physical health through the
      complex pathways linking psychological and biological factors. DESIGN: The
      present study investigates the relationships between body image satisfaction,
      inflammation (cytokine levels), aerobic fitness level and obesity in 96 middle
      aged men and women (48 normal and 48 overweight). All participants underwent
      measurements of body satisfaction, body composition, serological measurements of
      inflammation and aerobic capabilities assessment. RESULTS: Body image
      dissatisfaction uniquely predicted inflammation biomarkers, C-reactive protein
      and tumour necrosis factor-alpha, even when controlled for obesity indicators.
      Thus, body image dissatisfaction is strongly linked to inflammation processes and
      may promote the increase in cytokines, representing a relative metabolic risk,
      independent of most traditional risk factors, such as gender, body mass index and
      intra-abdominal (waist to hip ratio) adiposity. CONCLUSION: Results highlight the
      fact that person's negative cognitions need to be considered in psychologically
      based interventions and strategies in treatment of obesity, including strategies
      for health promotion. Results contribute to the knowledge base of the complex
      pathways in the association between psychological factors and physical illness
      and some important attempts were made to explain the psychological pathways
      linking cognitions with inflammation.

PMID- 24125029
TI  - Supercapacitor electrodes based on layered tungsten disulfide-reduced graphene
      oxide hybrids synthesized by a facile hydrothermal method.
AB  - We report here the synthesis of layer structured WS2/reduced graphene oxide (RGO)
      hybrids by a facile hydrothermal method for its possible application as
      supercapacitor materials in energy storage devices. The prepared two-dimensional
      materials are characterized thoroughly by various analytical techniques to
      ascertain their structure and to confirm the absence of any impurities. Two
      electrode capacitance measurements have been carried out in aqueous 1 M Na2SO4.
      The WS2/RGO hybrids exhibited enhanced supercapacitor performance with specific
      capacitance of 350 F/g at a scan rate of 2 mV/s. The obtained capacitance values
      of WS2/RGO hybrids are about 5 and 2.5 times higher than bare WS2 and RGO sheets.
      Because of the unique microstructure with combination of two layered materials,
      WS2/RGO hybrids emerge as a promising supercapacitor electrode material with high
      specific capacitance, energy density, and excellent cycling stability. 

PMID- 24125030
TI  - Management of an epidermoid cyst in the nasal tip of a child: aesthetic and
      surgical considerations.
AB  - BACKGROUND: A simple subcutaneous lesion such as an epidermoid cyst can present a
      challenge when located in the nasal tip, as regards aesthetic surgical
      management. Even when performed parallel to relaxed skin tension lines, a direct
      transcutaneous incision (commonly used for epidermoid cyst removal) distorts the
      nasal tip subunit, resulting in a conspicuous, disfiguring scar. This should be
      avoided, especially in children. CASE REPORT: A 13-year-old girl was referred by
      her dermatologist for diagnosis and treatment of a slowly progressive dermoid
      cyst located on the tip of her nose. The cyst was removed using a subcutaneous
      open rhinoplasty approach, leaving the aesthetic nasal tip subunit intact.
      CONCLUSION: For aesthetic reasons, open rhinoplasty should be considered as a
      treatment option in patients with subcutaneous lesions in the nasal tip.

PMID- 24125031
TI  - Time-dependent wave packet quantum scattering and quasi-classical trajectory
      calculations of the H + FCl(v=0,j=0) -> HF + Cl/HCl + F reaction.
AB  - The dynamics of the title reaction are investigated using both time-dependent
      wave packet quantum scattering and quasi-classical trajectory (QCT) methods on
      adiabatic ground 1(2)A' potential energy surface (PES). Compared with the quantum
      results of reaction probabilities of H + FCl(J=0) -> HF + Cl/HCl + F, the QCT
      method is proven feasible and further employed to produce integral cross sections
      and rate constants. Significant resonance structures are observed in the reaction
      probabilities using the quantum method; however, there are some undulations in
      the calculated QCT integral cross sections for both product channels. A
      comparison between the quantum mechanical coupled-channel (CC) calculation and
      centrifugal sudden approximation calculation reveals the very important role of
      Coriolis coupling effects in the quantum calculation. Comparisons between the
      calculated thermal rate constants for both reactions and the previous theoretical
      and experimental results have been done. HCl product formation is favored over
      the HF product in the reactive system. Finally, the HF products are found to be
      mainly forward scattering, and the HCl products are mainly backward scattering. 

PMID- 24125032
TI  - Assessment of cholesterol-derived ionic copolymers as potential vectors for gene
      delivery.
AB  - A library of cholesterol-derived ionic copolymers were previously synthesized via
      reversible addition-fragmentation chain transfer (RAFT) polymerization as 'smart'
      gene delivery vehicles that hold diverse surface charges. Polyplex systems formed
      with anionic poly(methacrylic acid-co-cholesteryl methacrylate) (P(MAA-co-CMA))
      and cationic poly(dimethylamino ethyl methacrylate-co-cholesteryl methacrylate)
      (Q-P(DMAEMA-co-CMA)) copolymer series were evaluated for their therapeutic
      efficiency. Cell viability assays, conducted on SHEP, HepG2, H460, and MRC5 cell
      lines, revealed that alterations in the copolymer composition (CMA mol %)
      affected the cytotoxicity profile. Increasing the number of cholesterol moieties
      in Q-P(DMAEMA-co-CMA) copolymers reduced the overall toxicity (in H460 and HepG2
      cells) while P(MAA-co-CMA) series displayed no significant toxicity regardless of
      the CMA content. Agarose gel electrophoresis was employed to investigate the
      formation of stable polyplexes and determine their complete conjugation ratios.
      P(MAA-co-CMA) copolymer series were conjugated to DNA through a cationic linker,
      oligolysine, while Q-P(DMAEMA-co-CMA)-siRNA complexes were readily formed via
      electrostatic interactions at conjugation ratios beginning from 6:1:1
      (oligolysine-P(MAA-co-CMA)-DNA) and 20:1 (Q-P(DMAEMA-co-CMA)-siRNA),
      respectively. The hydrodynamic diameter, zeta potential and complex stability of
      the polyplexes were evaluated in accordance to complexation ratios and copolymer
      composition by dynamic light scattering (DLS). The therapeutic efficiency of the
      conjugates was assessed in SHEP cells via transfection and imaging assays using
      RT-qPCR, Western blotting, flow cytometry, and confocal microscopy. DNA
      transfection studies revealed P(MAA-co-CMA)-oligolysine-DNA ternary complexes to
      be ineffective transfection vehicles that mostly adhere to the cell surface as
      opposed to internalizing and partaking in endosomal disrupting activity. The
      transfection efficiency of Q-P(DMAEMA-co-CMA)-GFP siRNA complexes were found to
      be polymer composition and N/P ratio dependent, with Q-2% CMA-GFP siRNA
      polyplexes at N/P ratio 20:1 showing the highest gene suppression in GFP
      expressing SHEP cells. Cellular internalization studies suggested that Q-P(DMAEMA
      co-CMA)-siRNA conjugates efficiently escaped the endolysosomal pathway and
      released siRNA into the cytoplasm. The gene delivery profile, reported herein,
      illuminates the positive and negative attributes of each therapeutic design and
      strongly suggests Q-P(DMAEMA-co-CMA)-siRNA particles are extremely promising
      candidates for in vivo applications of siRNA therapy. 

PMID- 24125033
TI  - Gridless overtone mobility spectrometry.
AB  - A novel overtone mobility spectrometry (OMS) instrument utilizing a gridless
      elimination mechanism and cooperative radio frequency confinement is described.
      The gridless elimination region uses a set of mobility-discriminating radial
      electric fields that are designed so that the frequency of field application
      results in selective transmission and elimination of ions. To neutralize ions
      with mobilities that do not match the field application frequency, active
      elimination regions radially defocus ions toward the lens walls. Concomitantly, a
      lens-dependent radio frequency waveform is applied to the transmission regions of
      the drift tube resulting in radial confinement for mobility-matched ions.
      Compared with prior techniques, which use many grids for ion elimination, the new
      gridless configuration substantially reduces indiscriminate ion losses. A
      description of the apparatus and elimination process, including detailed
      simulations showing how ions are transmitted and eliminated is presented. A
      prototype 28 cm long OMS instrument is shown to have a resolving power of 20 and
      is capable of attomole detection limits of a model peptide (angiotensin I) spiked
      into a complex mixture (in this case peptides generated from digestion of beta
      casein with trypsin). 

PMID- 24125034
TI  - Postvaccination bullous pemphigoid in infancy: report of three new cases and
      literature review.
AB  - Bullous pemphigoid (BP) is an acquired autoimmune blistering disorder of unknown
      etiology uncommon in childhood. Unlike adult BP, infantile BP shows acral
      distribution and resolves rapidly with systemic steroids. We report three infants
      with infantile BP presenting shortly after vaccination for diphtheria, pertussis,
      tetanus, poliomyelitis, hepatitis B, Haemophilus influenzae B, and meningococcus
      C. Our cases further reinforce the causal association between childhood BP and
      vaccination. 

PMID- 24125035
TI  - Targets for intervention to improve virological outcomes for patients receiving
      free antiretroviral therapy in Tamil Nadu, India.
AB  - Operational research to identify factors predicting poor clinical outcomes is
      critical to maximize patient care and prolong first-line regimens for those
      receiving free antiretroviral therapy (ART) in India. We sought to identify
      social or clinical factors amenable to intervention that predict virological
      outcomes after 12 months of ART. We examined a retrospective cohort of
      consecutive adults initiating free nonnucleoside reverse transcriptase inhibitor
      based regimens. Individuals remaining in care 12 months post-ART initiation were
      tested for HIV viral load and surveyed to identify barriers and facilitators to
      adherence, and to determine clinic travel times and associated costs. Uni- and
      multivariate logistic regression identified factors predicting HIV viral load
      >200 copies/mL after 12 months of ART. Of 230 adults initiating ART, 10% of
      patients died, 8% transferred out, 5% were lost to follow-up, and 174/230 (76%)
      completed 12 months of ART, the questionnaire, and viral load testing. HIV viral
      load was <200 copies/mL in 140/174 (80%) patients. In multivariate models, being
      busy with work or caring for others (OR 2.9, p < 0.01), having clinic transport
      times >= 3 hours (OR 3.0, p = 0.02), and alcohol use (OR 4.8, p = 0.03) predicted
      viral load >200 copies/mL after 12 months of ART. Clinical outcomes following ART
      are related to programmatic factors such as prolonged travel time and individual
      factors such as being busy with family or using alcohol. Simple interventions
      that alter these factors should be evaluated to improve clinical outcomes for
      populations receiving free ART in similar settings. 

PMID- 24125036
TI  - 1p36.22 region containing PGD gene is frequently gained in human cervical cancer.
AB  - AIM: To identify commonly occurring DNA copy number alterations in Korean
      cervical cancers. METHODS: DNA copy number alteration was screened by whole
      genome array comparative genomic hybridization (CGH) analysis. For the array CGH
      discovery, genomic DNA from five cervical cancers and 10 normal cervical tissues
      were examined. For the independent validation of the most significant chromosomal
      alteration (1p36.22, PGD gene), 40 formalin-fixed paraffin-embedded cervical
      tissue samples were collected; 10 of them were used for quantitative polymerase
      chain reaction and the other 30 samples were used for immunohistochemical
      analysis. Chromosomal segments differently distributed between cancers and normal
      controls were determined to be recurrently altered regions (RAR). RESULTS: A
      total of 13 RAR (11 RAR losses and two RAR gains) were defined in this study. Of
      the 13 cervical cancer-specific RAR, RAR gain in the 1p36.22 locus where the PGD
      gene is located was the most commonly detected in cancers (P = 0.004). In the
      quantitative polymerase chain reaction replication, copy number gain of the PGD
      gene was consistently identified in cervical cancers but not in the normal
      tissues (P = 0.02). In immunohistochemical analysis, PGD expression was
      significantly higher in cervical cancers than normal tissues (P = 0.02).
      CONCLUSION: Our results will be helpful to understand cervical carcinogenesis,
      and the PGD gene can be a useful biomarker of cervical cancer.

PMID- 24125037
TI  - Effect of water-soluble titanium microparticle-permeated tape on
      temporomandibular disorders-related pain: a preliminary study.
AB  - OBJECTIVE: Recent research has focused on the applicability of titanium particle
      impregnated materials in healthcare and medical products. This preliminary study
      was undertaken to investigate the effect of water-soluble titanium microparticle
      permeated (WSTi) tape on temporomandibular disorder (TMD)-related pain. MATERIALS
      AND METHODS: The study included 32 patients (41.5 +/- 14.4 years, 26 women) who
      had visited the Temporomandibular Joint Clinic, Tokyo Medical and Dental
      University, for treatment of TMD-related pain. The subjects were instructed to
      apply the WSTi tape (AquaTitan tape) on the most painful area before going to
      sleep and remove the tape on awakening daily for 2 weeks. Seven outcome variables
      were statistically analyzed: maximum mouth-opening ranges with and without pain,
      spontaneous pain intensity, mouth-opening pain intensity, chewing pain intensity,
      TMD-related limitation of daily functions (LDF-TMD) and subjective evaluation of
      any change in TMD-related pain. RESULTS: The mean maximum mouth-opening ranges
      with (p = 0.011) and without (p = 0.002) pain were significantly greater and mean
      pain intensities on mouth opening (p < 0.001) and chewing (p = 0.001) were
      significantly lower at the 2-week follow-up than at the baseline. The mean LDF
      TMDQ scores were also significantly lower at the 2-week follow-up (p = 0.004).
      After 2 weeks of using the WSTi tape, 53.1% and 12.5% of the subjects reported a
      slight improvement and an improvement, respectively, in TMD-related pain.
      CONCLUSION: WSTi tape seems to have beneficial effects on TMD-related pain and
      LDF.

PMID- 24125038
TI  - X-ray irradiation alters the actin cytoskeleton in murine lacrimal glands.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of X radiation on
      the distribution of filamentous actin (F-actin) in the mouse exorbital lacrimal
      gland. MATERIALS AND METHODS: Mice were divided into groups that received no
      radiation (n = 6) or one single exposure of 36 mGy of X radiation (n = 12). The
      animals were sacrificed after 4, 8 or 24 h. The lacrimal glands were stained with
      Hematoxylin/Eosin or Rhodamine-phalloidin and the filamentous actin arrangement
      was analyzed by confocal microscopy. RESULTS: After 4 h of X-ray exposure there
      was an apparent increase in acini area and a decrease in the cortical F-actin
      content in secretory cells. This effect decreased gradually over time, returning
      to values close to the control after 24 h. CONCLUSION: This study shows that a 36
      mGy diagnostic X-ray dose affected reversibly the mouse exorbital lacrimal gland,
      suggesting that radiation used in diagnosis may induce changes on cell morphology
      due to actin remodeling.

PMID- 24125039
TI  - Time-lapse AFM imaging of DNA conformational changes induced by daunorubicin.
AB  - Cancer is a major health issue that absorbs the attention of a large part of the
      biomedical research. Intercalating agents bind to DNA molecules and can inhibit
      their synthesis and transcription; thus, they are increasingly used as drugs to
      fight cancer. In this work, we show how atomic force microscopy in liquid can
      characterize, through time-lapse imaging, the dynamical influence of
      intercalating agents on the supercoiling of DNA, improving our understanding of
      the drug's effect. 

PMID- 24125040
TI  - Gallium-doped tin oxide nano-cuboids for improved dye sensitized solar cell.
AB  - Tin dioxide (SnO2) is a potential candidate to replace conventional titanium
      dioxide (TiO2) in dye-sensitized solar cells (DSSCs) because of its wider bandgap
      and higher electron mobility. However, SnO2 suffers from low band edge that
      causes severe backflow of electrons towards electrolyte (charge recombination).
      Herein, we demonstrate that gallium (Ga) doping can increase the band edge of
      SnO2, and we show that DSSCs using a Ga-doped SnO2 nano-cuboids based photoanode
      offer improved open circuit potential (~0.74 V), fill factor (~73.7%), and power
      conversion efficiency (~4.05%).

PMID- 24125041
TI  - Computational study of nanoparticle dispersion and spatial distribution in
      polymer matrix under oscillatory shear flow.
AB  - In this work, nonequilibrium molecular dynamics simulations were performed to
      investigate the dispersion and spatial distribution of spherical nanoparticles
      (NPs) in polymer matrix under oscillatory shear flow. We systematically analyzed
      the influences of four important factors that consist of NP-polymer interfacial
      strength, volume fraction of NPs, shear conditions, and polymer chain length. The
      simulation results showed that the oscillatory shear can greatly improve the
      dispersion of NPs, especially for the polymer nanocomposites (PNCs) with high NP
      polymer interfacial strength. Under specific shear conditions, the NPs can
      exhibit three different spatial distribution states with increasing the NP
      polymer interfacial strength. Interestingly, at high interfacial strength, we
      observed that the NPs can be distributed on several layers in the polymer matrix,
      forming the PNCs with sandwich-like structures. Such well-ordered nanocomposites
      can exhibit a higher tensile strength than those with the NPs dispersed randomly.
      It may be expected that the information derived in present study provides a
      useful foundation for guiding the design and preparation of high-performance
      PNCs. 

PMID- 24125042
TI  - Role of the metal in the bonding and properties of bimetallic complexes involving
      manganese, iron, and cobalt.
AB  - A multidentate ligand platform is introduced that enables the isolation of both
      homo- and heterobimetallic complexes of divalent first-row transition metal ions
      such as Mn(II), Fe(II), and Co(II). By means of a two-step metalation strategy,
      five bimetallic coordination complexes were synthesized with the general formula
      M1M2Cl(py3tren), where py3tren is the triply deprotonated form of N,N,N-tris(2-(2
      pyridylamino)ethyl)amine. The metal-metal pairings include dicobalt (1), cobalt
      iron (2), cobalt-manganese (3), diiron (4), and iron-manganese (5). The
      bimetallic complexes have been investigated by X-ray diffraction and X-ray
      anomalous scattering studies, cyclic voltammetry, magnetometry, Mossbauer
      spectroscopy, UV-vis-NIR spectroscopy, NMR spectroscopy, combustion analyses,
      inductively coupled plasma optical emission spectrometry, and ab initio quantum
      chemical methods. Only the diiron chloride complex in this series contains a
      metal-metal single bond (2.29 A). The others show weak metal-metal interactions
      (2.49 to 2.53 A). The diiron complex is also distinct with a septet ground state,
      while the other bimetallic species have much lower spin states from S = 0 to S =
      1. We propose that the diiron system has delocalized metal-metal bonding
      electrons, which seems to correlate with a short metal-metal bond and a higher
      spin state. Multiconfigurational wave function calculations revealed that,
      indeed, the metal-metal bonding orbitals in the diiron complex are much more
      delocalized than those of the dicobalt analogue. 

PMID- 24125043
TI  - Severe acute illness in a toddler exposed to multiple agricultural pesticides and
      an insect repellent.
AB  - Acute severe pesticide-related illness among farm worker children is rarely
      reported. The authors report a toddler with acute onset of apnea, cyanosis,
      somnolence, hypotonia, tachycardia, and miosis who required hospitalization.
      Health care providers suspected pesticide poisoning, but were unable to determine
      the causal agent. Investigation by a public health program documented four
      pesticide exposures that occurred within one-half hour of acute illness. This
      case illustrates the importance of a thorough environmental/occupational exposure
      history and obtaining biological samples. It also documents the need to
      strengthen the Worker Protection Standard for agricultural workers and the
      importance of reporting and investigating pesticide-related illness.

PMID- 24125044
TI  - Needs assessment for reducing pesticide risk: a case study with farmers in
      Vietnam.
AB  - The objective of this study was to identify the needs for and solutions to
      pesticide risk reduction for farmers in Vietnam, using a comprehensive needs
      assessment model applied for evaluating community needs and policy development.
      Four kinds of needs were evaluated using qualitative research methods. A
      comparative analysis of pesticide regulations was used to identify comparative
      needs. In-depth interviews with authorities and experts were conducted to
      identify normative needs. Observations on farmer's practice were used to identify
      expressed needs, and focus group discussions among farmers were implemented to
      identify felt needs. The needs for pesticide regulations obtained from
      comparative analysis and experts include enhancement of pesticide legislation;
      multisectoral involvement in pesticide regulations; improvement of capacity for
      sectors involving in pesticide regulations; risk-benefit guidance for pesticide
      registration; reforms of pesticide regulations relating to the restriction,
      cancellation, suspension, transport, storage, and disposal of pesticides; and the
      development of occupational hygiene and safety policy and programs for
      agricultural activities. The expressed needs based on field observations comprise
      improvement in knowledge and behavior of farmers about pesticide safety with
      specific areas, and supports in safety facilities and personal protective
      equipment. The key request from farmers include needs about technical training
      for occupational safety and hygiene of pesticide application, and support for
      safety facilities for pesticide application and protective equipment. The results
      of comprehensive needs assessment were useful in the development of a range of
      strategies in legislative improvement, workplace and personal hygiene,
      information and training, and medical surveillance and pesticide poisoning first
      aids for pesticide risk reduction for Vietnamese farmers.

PMID- 24125045
TI  - Swine worker awareness and behavior regarding prevention of zoonotic influenza
      transmission.
AB  - ABSTRACT A convenience survey of swine workers on large and small commercial
      farms in the Northeast and Midwest United States regarding zoonotic influenza
      awareness and precautions was conducted. Workers reported low levels of concern
      regarding the risk of contracting influenza from swine, and were generally not
      aware of national guidelines for influenza prevention. Use of personal protective
      equipment (PPE) varied by task, N95 respirator use was rare, and no workers were
      enrolled in respirator programs. Reported influenza vaccination coverage was
      greater than the national average in 2009-2010, but declined in 2010-2011.
      Workers on large farms were more likely to use PPE in some tasks and to report
      using more precautions when pigs appeared ill. Although reporting low levels of
      concern regarding zoonotic influenza and low adherence to national influenza
      guidelines, swine workers reported making task-based and risk-based decisions
      about use of PPE, suggesting opportunities for enhanced prevention of zoonotic
      disease transmission. 

PMID- 24125046
TI  - Occupational health among Latino horse and crop workers in Kentucky: the role of
      work organization factors.
AB  - Agriculture is a dangerous industry often reliant on Latino workers, a vulnerable
      population. Using a work organization framework, this cross-sectional study
      analyzes the relationship between work organization variables and the
      occupational health of Latino crop (n = 49) and horse breeding (n = 54) workers
      in Kentucky. Increased levels of abusive supervision were associated with
      occupational injury (odds ratio [OR] = 2.97; 95% confidence interval [CI]: 1.0
      8.77) and increased awkward postures were associated with occupational illness
      (OR = 3.85; 95% CI: 1.06-13.98). Although not statistically significant, abusive
      supervision increased the odds and a high safety climate score decreased the odds
      of injury, illness, and missed work. These findings suggest that the supervisor
      subordinate relationship may play a critical role in the occupational health of
      Latino farmworkers.

PMID- 24125047
TI  - Pesticide use practices in rural Armenia.
AB  - Pesticide use can have adverse effects on both human health and the environment.
      Inappropriate use of pesticides increases the health risk to those who work with
      or live around pesticides. Educational programs for agricultural workers on the
      proper use of pesticides and personal protective equipment coupled with pesticide
      regulations are important tools to reduce the associated health risks. The
      authors conducted a survey (N = 2336) on pesticide use practices in the Ararat
      Valley of Armenia in 2000-2006. This study was a cross-sectional design. A
      multistage sampling method was implemented in the selection of the study
      population. The authors developed a questionnaire containing 173 questions to
      evaluate demographic characteristics, health conditions, and details of
      pesticides use practices. The intensity of pesticide use was high; 82.8% of
      respondents used them. More than 150 brand names of pesticides were in use.
      Unregistered, obsolete, expired, and banned compounds were found in active use.
      Poor compliance with the basic rules of pesticide safety was found throughout the
      study population, with 21.3% using gloves and only 11% using respirators. The
      agricultural workers' knowledge of the toxic properties of these pesticides as
      well as basic hygienic norms was very low. In some instances, the number of
      agrichemical applications to crops, particularly cucumbers and melons, reached 40
      applications during the growing season. Better protection and training of
      pesticide users in Armenia is needed.

PMID- 24125048
TI  - Electronic merger of large health care data sets: cautionary notes from a study
      of agricultural morbidity in New York State.
AB  - Agriculture ranks among industries with the highest rates of occupational injury
      and fatality. Administrative medical data sets have long been thought to have
      potential for occupational injury surveillance. This research explores the
      feasibility of establishing an agricultural injury surveillance system in New
      York State that combines data from existing electronic sources. Prehospital Care
      Report (PCR) data containing the nature of the accident, type of injury, time and
      date, and patient disposition were received. Researchers also obtained both
      hospital inpatient and emergency department (ED) records for 2007 through 2009
      from the Statewide Planning and Research Cooperative System (SPARCS). For SPARCS
      data, a computer algorithm identified all potential cases of agricultural injury
      using International Classification of Diseases (ICD)-9 codes. An attempt was then
      made to match PCR and SPARCS data using accident date, gender, age, and admitting
      hospital. Of the PCR records that were matched to SPARCS, 46.8% were found on
      subsequent inspection to not actually relate to the same incident. Total PCR
      counts for 2007 and 2008 showed considerable fluctuation, at 2,512,828 and
      2,948,841, respectively. A total of 1275, 1336, and 1393 farm injuries were
      identified in the SPARCS records for 2007, 2008, and 2009, respectively. This
      study demonstrates that accurate matching of PCR and SPARCS records requires the
      use of unique personal identifiers. Further, annual fluctuations in PCR counts
      preclude their current use in a surveillance system. An electronic data set
      consisting of SPARCS data could be used for surveillance, but would benefit from
      the addition of PCR data as these become more consistent.

PMID- 24125049
TI  - Structural equation modeling of pesticide poisoning, depression, safety, and
      injury.
AB  - The role of pesticide poisoning in risk of injuries may operate through a link
      between pesticide-induced depressive symptoms and reduced engagement in safety
      behaviors. The authors conducted structural equation modeling of cross-sectional
      data to examine the pattern of associations between pesticide poisoning,
      depressive symptoms, safety knowledge, safety behaviors, and injury. Interviews
      of 1637 Colorado farm operators and their spouses from 964 farms were conducted
      during 1993-1997. Pesticide poisoning was assessed based on a history of ever
      having been poisoned. The Center for Epidemiologic Studies-Depression scale was
      used to assess depressive symptoms. Safety knowledge and safety behaviors were
      assessed using ten items for each latent variable. Outcomes were safety behaviors
      and injuries. A total of 154 injuries occurred among 1604 individuals with
      complete data. Pesticide poisoning, financial problems, health, and age predicted
      negative affect/somatic depressive symptoms with similar effect sizes; sex did
      not. Depression was more strongly associated with safety behavior than was safety
      knowledge. Two safety behaviors were significantly associated with an increased
      risk of injury. This study emphasizes the importance of financial problems and
      health on depression, and provides further evidence for the link between
      neurological effects of past pesticide poisoning on risk-taking behaviors and
      injury.

PMID- 24125050
TI  - Female farmworkers' perceptions of heat-related illness and pregnancy health.
AB  - Although agricultural workers have elevated risks of heat-related illnesses
      (HRI), pregnant farmworkers exposed to extreme heat face additional health risk,
      including poor pregnancy health and birth outcomes. Qualitative data from five
      focus groups with 35 female Hispanic and Haitian nursery and fernery workers
      provide details about the women's perceptions of HRI and pregnancy. Participants
      believe that heat exposure can adversely affect general, pregnancy, and fetal
      health, yet feel they lack control over workplace conditions and that they lack
      training about these specific risks. These data are being used to develop
      culturally appropriate educational materials emphasizing health promoting and
      protective behaviors during pregnancy.

PMID- 24125051
TI  - Occupational incidents with self-propelled machinery in Austrian agriculture.
AB  - Tractors, self-propelled harvesting machinery, and material handling machinery
      are the most commonly used self-propelled machineries in Austrian agriculture,
      and they have similarities in main accident scenarios. Statistical data of all
      occupational incidents with these machines reported between 2008 and 2010 were
      analyzed to obtain information about the circumstances of the incidents, and
      about the victims and their work environments. Criteria of recognized
      occupational incidents provided by the Austrian Social Insurance Institution for
      Farmers were analyzed according to machinery category by means of cross
      tabulation and chi-square tests. The results were discussed and evaluated in the
      context of the literature. The results of the analysis of the databases show that
      786 occupational incidents with tractors, self-propelled harvesting machinery,
      and material handling machinery occurred in Austrian agriculture between 2008 and
      2010. There were 231 occupational incidents in 2008; the number rose to 268 in
      2009 and to 286 in 2010. A total of 41 incidents were fatal. For the machinery
      categories analyzed, the majority of injured victims were male, older than 40
      years, Austrian citizens, and managers of a mixed-agricultural farm. A large
      number of the incidents occurred in all machinery categories by loss of control
      during operating a vehicle.

PMID- 24125052
TI  - Preliminary ergonomic evaluation of barn tasks in intensive swine production.
AB  - This exploratory pilot study analyses musculoskeletal symptoms and working
      exposures of intensive pig barn tasks. Methods included a questionnaire phase to
      gather information about workers' symptoms and video analysis to assess exposures
      during typical production tasks. Ninety-two percent of workers reported symptoms
      in the last 12 months in any body part; 58% reported interruption of work
      activities in the last 12 months. The task "moving dead pigs" exceeded 3400 N
      during 6 of 18 observations. Frequency of hand gripping and trunk bending >45
      degrees were moderate to high in many tasks. These biomechanical exposures
      suggest a need for further study, particularly on interventions to limit bending,
      lifting, and repetitive gripping.

PMID- 24125054
TI  - The association between adverse life events and body weight change: results of a
      prospective cohort study.
AB  - BACKGROUND: Stress has been shown to be a determinant of weight change and risk
      for obesity. To date, there is scarce evidence that stressful life events and
      their severity contribute to changes in body weight. We studied the association
      between the occurrence, impact of and adaptation to adverse life events and
      weight change and the role of initial weight status. METHODS: Analyses were based
      on data from a population-based cohort of 2789 adults. Adverse life events, their
      impact and adaptation were measured retrospectively after baseline and follow-up
      weight and height measurements. RESULTS: Over six years, participants gained an
      average of 2.8 kg. There were no differences in weight change between those who
      had experienced an adverse life event versus those who had not. However, the
      impact of life events had a significant interaction with initial weight status.
      Adults with a healthy weight showed an average weight reduction of 0.2 kg (95%
      CIs: -0.7 - 0.2), and overweight adults showed an average weight gain of 0.4 kg
      (95% CIs: -0.3 - 1.1) for each point increase in impact after experiencing an
      adverse life event. Further, a slower adaptation to events was significantly
      associated with greater weight loss among those who lost weight. CONCLUSIONS: We
      found no proof for an association between life events and weight change in the
      entire study sample, but we found that adults at a healthy weight responded
      differently to adverse life events than those who were overweight.

PMID- 24125055
TI  - Affinity enhancement of HER2-binding Z(HER2:342) affibody via rational design
      approach: a molecular dynamics study.
AB  - Human epidermal growth factor receptor 2 (HER2) contributes to the development of
      breast cancers and malignancies. On the other hand, engineered affibody
      Z(HER2:342) that binds to HER2 can be successfully used for both diagnostic
      purposes and specific ablation of malignant HER2-positive cell lines. In the
      current study, electrostatics-based prediction was applied for improving
      Z(HER2:342) binding affinity using computational design. The affibody Z(HER2:342)
      alone and in complex with HER2 was energetically minimized, solvated in explicit
      water, and neutralized. After heating and equilibration steps, the system was
      studied by isothermal-isobaric (NPT) MD simulation. According to trajectories,
      Z(HER2:342) specifically binds to HER2 through hydrogen bonds and salt bridges.
      Based on the electrostatic binding contributions, two affinity-matured variants
      namely V1 (Tyr35Arg) and V2 (Asn6Asp and Met9Glu) were rationally designed. More
      investigations through MD simulation show that V1 interacts with HER2 receptor
      more strongly, compared to Z(HER2:342) and V2. 

PMID- 24125056
TI  - Effect of a novel dietary supplement on pH levels of healthy volunteers: a pilot
      study.
AB  - OBJECTIVE: To examine the effects of a greens alkalizing dietary supplement on
      urinary pH levels in individuals with lower-than-average pH levels. METHODS: The
      present study investigated the effects of an alkalizing formula (Reserveage
      Wholeganic Greens(TM)) on four individuals who had average urinary pH levels
      below 6.0 for three consecutive days. Following the three-day, baseline period,
      participants received Reserveage Wholeganic Greens(TM) for four consecutive days
      and were instructed to continue to measure their urine pH levels. Paired samples
      t-tests were used to examine pH levels before and after a four-day treatment
      period with Reserveage Wholeganic Greens(TM). RESULTS: Compared to baseline, mean
      urine pH levels in all volunteers were significantly higher following the
      supplementation with Reserveage Wholeganic Greens(TM) (5.89 +/- 0.20 vs 5.56 +/-
      0.23; P<0.01). Participants' pH levels were also significantly higher than
      baseline on days 5, 6, and 7 of the treatment period (P < 0.05). Noteworthy, on
      day 7, participants' mean pH levels were significantly higher than at the
      beginning of the treatment period (6.03 +/- 0.15 at day 7 vs 5.65 +/- 0.24 at day
      4; P < 0.01). CONCLUSION: The findings of this study suggest that supplementation
      with Reserveage Wholeganic Greens(TM) has an alkalizing effect on the body and
      can increase the urine pH levels in individuals with lower-than-average pH
      levels.

PMID- 24125057
TI  - Mechanism of resveratrol on the promotion of induced pluripotent stem cells.
AB  - OBJECTIVE: To investigate the effects of resveratrol (RV) in reprogramming mouse
      embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) and the
      related mechanism. METHODS: Primary MEFs were isolated from E13.5 embryos and
      used within three passages. Retroviruses expressing Sox2 and Oct4 were produced
      by transfecting GP2-293t cells with recombinant plasmids (MSCV)-Sox2 and MSCV
      Oct4. Supernatants containing retroviruses were obtained after 48-hour
      transfection and MEFs were then infected. Different concentrations (0, 5, 10 and
      20 MUmol/L) of RV were added to embryonic stem cell (ESC) medium to culture MEFs
      48 h post-infection. iPSC clones emerged and were further cultured. Expression of
      pluripotent markers of iPSCs was identified by cell immunofluorescence and
      reverse transcription-polymerase chain reaction. Both cytotoxicity and cell
      proliferation were assayed by Western blot analysis after RV was added into ESC
      medium. The ultrastructure change of mitochondria was observed by electron
      microscopy. RESULTS: More than 2.9-fold and 1.3-fold increases in colony number
      were observed by treatment with RV at 5 and 10 MUmol/L, respectively. The
      reprogramming efficiency was significantly decreased by treatment with 20 MUmol/L
      RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 (2
      factors-MEFs, 2F-MEFs) was investigated after RV treatment. At 20 MUmol/L RV,
      induced cell apoptosis and proliferation inhibition were more obvious than those
      of 5 and 10 MUmol/L treatments. Clones were selected from the 10 MUmol/L RV
      treated group and cultured. Green fluorescent protein expression from one typical
      clone was silenced one month later which expressed ESC-associated marker genes
      Gdf3, Nanog, Ecat1, Fgf4 and Foxd3. Electron transmission microscope showed
      obvious cavitations in mitochondria. The expression of hypoxia-inducible factor
      1alpha was up-regulated when 2F-MEFs were treated with RV compared to the control
      group. CONCLUSION: RV improved the efficiency of reprogramming 2F-MEFs into iPSCs
      at low and moderate concentrations (5 and 10 MUmol/L). The effect of 10 MUmol/L
      RV on reprogramming was much greater than that of 5 MUmol/L RV. However, high
      concentration of RV (20 MUmol/L) led to more severe cavitations in mitochondria
      and caused cytotoxic effects. Taken together, these findings suggest that RV
      mimics hypoxia in cells and promotes reprogramming at a low concentration.

PMID- 24125058
TI  - Synchrotron photoionization mass spectrometry measurements of product formation
      in low-temperature n-butane oxidation: toward a fundamental understanding of
      autoignition chemistry and n-C4H9 + O2/s-C4H9 + O2 reactions.
AB  - Product formation in the laser-initiated low-temperature (575-700 K) oxidation of
      n-butane was investigated by using tunable synchrotron photoionization time-of
      flight mass spectrometry at low pressure (~4 Torr). Oxidation was triggered
      either by 351 nm photolysis of Cl2 and subsequent fast Cl + n-butane reaction or
      by 248 nm photolysis of 1-iodobutane or 2-iodobutane. Iodobutane photolysis
      allowed isomer-specific preparation of either n-C4H9 or s-C4H9 radicals.
      Experiments probed the time-resolved formation of products and identified
      isomeric species by their photoionization spectra. For stable primary products of
      butyl + O2 reactions (e.g., butene or oxygen heterocycles) bimodal time behavior
      is observed; the initial prompt formation, primarily due to chemical activation,
      is followed by a slower component arising from the dissociation of thermalized
      butylperoxy or hydroperoxybutyl radicals. In addition, time-resolved formation of
      C4-ketohydroperoxides (C4H8O3, m/z = 104) was observed in the n-C4H9 + O2 and Cl
      initiated oxidation experiments but not in the s-C4H9 + O2 measurements,
      suggesting isomeric selectivity in the combined process of the "second" oxygen
      addition to hydroperoxybutyl radicals and subsequent internal H
      abstraction/dissociation leading to ketohydroperoxide + OH. To further constrain
      product isomer identification, Cl-initiated oxidation experiments were also
      performed with partially deuterated n-butanes (CD3CH2CH2CD3 and CH3CD2CD2CH3).
      From these experiments, the relative yields of butene product isomers (cis-2
      butene, trans-2-butene, and 1-butene) from C4H8 + HO2 reaction channels and
      oxygenated product isomers (2,3-dimethyloxirane, 2-methyloxetane,
      tetrahydrofuran, ethyloxirane, butanal, and butanone) associated with OH
      formation were determined. The current measurements show substantially different
      isomeric selectivity for oxygenated products than do recent jet-stirred reactor
      studies but are in reasonable agreement with measurements from butane addition to
      reacting H2/O2 mixtures at 753 K. 

PMID- 24125059
TI  - Striae distensae: a comprehensive review and evidence-based evaluation of
      prophylaxis and treatment.
AB  - Striae distensae are an extremely common, therapeutically challenging form of
      dermal scarring. Risk factors have been reported but much remains to be
      understood about their epidemiology, diagnosis and treatment. Up-to-date
      knowledge of the scientific research and the evidence behind both preventative
      and therapeutic agents are vital in order to understand striae and to offer
      patients the best therapeutic alternatives. We present a clinical review of the
      current literature concerning striae distensae and their prevention and
      treatment. A systematic review of the literature was undertaken using Medline,
      Embase and Google Scholar. Articles in English, Spanish, Portuguese, Turkish and
      French were included. Striae distensae occur in pregnancy, puberty and obesity as
      well as in numerous medical conditions and following therapeutic interventions.
      Proposed aetiological mechanisms relate to hormones, physical stretch and
      structural alterations to the integument. Assessment methods include subjective
      visual scoring and various imaging modalities. Treatments that we have evaluated
      include topical agents, used prophylactically or therapeutically, as well as
      light and laser therapies, which have shown improvements in the appearance of
      striae. Few high level evidence based medicine randomized controlled trials
      evaluating treatments for striae distensae exist. Topical therapeutic agents
      appear to lack efficacy in the prevention of striae distensae. 

PMID- 24125060
TI  - Effects of water availability on emerald ash borer larval performance and phloem
      phenolics of Manchurian and black ash.
AB  - The invasive emerald ash borer (EAB) beetle is a significant threat to the
      survival of North American ash. In previous work, we identified putative
      biochemical and molecular markers of constitutive EAB resistance in Manchurian
      ash, an Asian species co-evolved with EAB. Here, we employed high-throughput high
      performance liquid chromatography with photodiode array detection and mass
      spectrometry (HPLC-PDA-MS) to characterize the induced response of soluble phloem
      phenolics to EAB attack in resistant Manchurian and susceptible black ash under
      conditions of either normal or low water availability, and the effects of water
      availability on larval performance. Total larval mass per tree was lower in
      Manchurian than in black ash. Low water increased larval numbers and mean larval
      mass overall, but more so in Manchurian ash. Low water did not affect levels of
      phenolics in either host species, but six phenolics decreased in response to EAB.
      In both ashes, pinoresinol A was induced by EAB, especially in Manchurian ash.
      Pinoresinol A and pinoresinol B were negatively correlated with each other in
      both species. The higher accumulation of pinoresinol A in Manchurian ash after
      attack may help explain the resistance of this species to EAB, but none of the
      responses measured here could explain increased larval performance in trees
      subjected to low water availability.

PMID- 24125061
TI  - Characteristics of nursing home residents and physical restraint: a systematic
      literature review.
AB  - AIMS AND OBJECTIVES: To analyse and to summarise factors associated with nursing
      home residents' characteristics which could lead to physical restraint, and to
      investigate the consequences of physical restraint use for this population.
      BACKGROUND: Even though the application of physical restraint is highly
      controversial, prevalence rates show that it is a common intervention in nursing
      homes. Residents' characteristics seem to be important to predict the use of
      physical restraint. Evidence suggests that restrained nursing home residents may
      have physical and psychological disadvantages as a consequence of being
      restrained. METHODS: A systematic literature research involving the databases
      PubMed, Cumulative Index to Nursing and Allied Health Literature, ISI Web of
      Science and Cochrane Library was carried out for articles published from January
      2005-November 2011. Nine Studies fulfilled the inclusion criteria and the quality
      assessment. RESULTS: Restrained residents had low activities of daily living
      (ADL) scores and severe cognitive impairment. Residents with low cognitive status
      and serious mobility impairments were at high risk to be restrained, as well as
      residents with previous fall and/or fracture. Repeated verbal and physical
      agitation was found to be positively associated with restraint use. Possible
      consequences of physical restraint were as follows: lower cognitive and ADL
      performance, higher walking dependence, furthermore falls, pressure ulcers,
      urinary and faecal incontinence. CONCLUSIONS: This systematic literature review
      reveals notable resident-related factors for physical restraint use. The
      consequences of restraint seem to negatively influence residents' physical and
      psychological well-being. Physical restraint seems to be an important risk factor
      for residents' further health problems. RELEVANCE TO CLINICAL PRACTICE:
      Resident's characteristics appear to be decisive factors for the use of physical
      restraint. Nurses need a high level of expertise and competence in evaluating the
      individual residents' situation and deciding further steps, with respect for the
      autonomy and dignity of the person.

PMID- 24125062
TI  - Transoral robotic resection of lingual thyroid: case report.
AB  - OBJECTIVE: We present a case of large, symptomatic lingual thyroid which was
      successfully and safely removed via a transoral approach, using the da Vinci
      robotic system, in an academic medical centre in Singapore. CASE REPORT: A 17
      year-old female adolescent presented with a large lingual thyroid causing upper
      airway obstruction. She underwent robotic, minimally invasive, transoral
      resection using the da Vinci system. Post-operative recovery was uneventful; she
      was able to commence oral feeding almost immediately, and was discharged from
      hospital on the fourth post-operative day. CONCLUSION: It is surgically feasible
      and safe to undertake transoral robotic resection of a large lingual thyroid.
      This approach may allow faster recovery and shorter hospitalisation for patients.
      Surgical safety requires a full understanding of the intralingual neurovascular
      anatomy.

PMID- 24125063
TI  - Fabrication of free-standing ZnMn2O4 mesoscale tubular arrays for lithium-ion
      anodes with highly reversible lithium storage properties.
AB  - In this paper, ZnMn2O4 mesoscale tubular arrays on current collectors were
      successfully synthesized using a reactive template route combined with a
      postcalcination process through the shape-preserving conversion of ZnO nanorod
      arrays in aqueous solutions at room temperature. On the basis of the experimental
      analyses, including X-ray diffraction, Raman spectroscopy, scanning electron
      microscopy, and transmission electron microscopy, a plausible formation mechanism
      of ZnMn2O4 tubular arrays was proposed in which solid ZnO nanorods are gradually
      transformed to ZnMn2O4 tubules via a simple cation exchange process between
      Zn(2+) and Mn(2+), followed by a postannealing process. Moreover, the lithium
      storage properties of the as-prepared ZnMn2O4 tubular structures were
      investigated by applying the structures as an active electrode material without
      auxiliary additives. The ZnMn2O4 array electrodes showed an excellent discharge
      capacity of ca. 1198.3 mAh g(-1) on the first cycle and exhibited outstanding
      cycling durability, rate capability, and Coulombic efficiency. These results
      indicate that the free-standing tubular array architectures of ZnMn2O4 prepared
      directly on the current collector can be powerful candidates for a highly
      reversible lithium storage electrode platform. 

PMID- 24125064
TI  - Video laryngoscopy improves intubation success and reduces esophageal intubations
      compared to direct laryngoscopy in the medical intensive care unit.
AB  - INTRODUCTION: Tracheal intubation in the Intensive Care Unit (ICU) can be
      challenging as patients often have anatomic and physiologic characteristics that
      make intubation particularly difficult. Video laryngoscopy (VL) has been shown to
      improve first attempt success compared to direct laryngoscopy (DL) in many
      clinical settings and may be an option for ICU intubations. METHODS: All
      intubations performed in this academic medical ICU during a 13-month period were
      entered into a prospectively collected quality control database. After each
      intubation, the operator completed a standardized form evaluating multiple
      aspects of the intubation including: patient demographics, difficult airway
      characteristics (DACs), method and device(s) used, medications used, outcomes and
      complications of each attempt. Primary outcome was first attempt success.
      Secondary outcomes were grade of laryngoscopic view, ultimate success, esophageal
      intubations, and desaturation. Multivariate logistic regression was performed for
      first attempt and ultimate success. RESULTS: Over the 13-month study period
      (January 2012-February 2013), a total of 234 patients were intubated using VL and
      56 patients were intubated with DL. First attempt success for VL was 184/234
      (78.6%; 95% CI 72.8 to 83.7) while DL was 34/56 patients (60.7%; 95% CI 46.8 to
      73.5). Ultimate success for VL was 230/234 (98.3%; 95% CI 95.1 to 99.3) while DL
      was 52/56 patients (91.2%; 95% CI 81.3 to 97.2). In the multivariate regression
      model, VL was predictive of first attempt success with an odds ratio of 7.67 (95%
      CI 3.18 to 18.45). VL was predictive of ultimate success with an odds ratio of
      15.77 (95% CI 1.92 to 129). Cormack-Lehane I or II view occurred 199/234 times
      (85.8%; 95% CI 79.5 to 89.1) and a median POGO (Percentage of Glottic Opening) of
      82% (IQR 60 to 100) with VL, while Cormack-Lehane I or II view occurred 34/56
      times (61.8%; 95% CI 45.7 to 71.9) and a median POGO of 45% (IQR 0 to 78%) with
      DL. VL reduced the esophageal intubation rate from 12.5% with DL to 1.3% (P =
      0.001) but there was no difference in desaturation rates. CONCLUSIONS: In the
      medical ICU, video laryngoscopy resulted in higher first attempt and ultimate
      intubation success rates and improved grade of laryngoscopic view while reducing
      the esophageal intubation rate compared to direct laryngoscopy.

PMID- 24125065
TI  - A longitudinal VBM study in paediatric obsessive-compulsive disorder at 2-year
      follow-up after cognitive behavioural therapy.
AB  - OBJECTIVES: To identify neurodevelopmental differences in regional brain volume
      between medication-free paediatric obsessive-compulsive disorder (OCD) patients
      and controls at 2-year follow-up after cognitive behavioural therapy. METHODS: We
      assessed 17 medication-free paediatric OCD patients (mean age 13.8 years; SD =
      2.8; range 8.2-19.0) and 20 controls, matched on age and gender, with T1-weighted
      MR scans in a repeated measures design at three time points with intervals of 6
      months and 2 years. Voxel based morphometry (VBM) was used to test whole brain
      voxel-wise for the effects of diagnosis and time on regional grey matter (GM) and
      white matter volumes. RESULTS: GM volume of the orbitofrontal cortex showed a
      group * time interaction effect, driven by an increase of GM volume over the
      whole time period in OCD patients and a decrease in controls. When splitting the
      groups in two age groups (8-12 and 13-19 years) this interaction effect was only
      seen in the youngest age group. CONCLUSIONS: Neuroimaging findings in paediatric
      OCD after 6 months of CBT in the GM volume of the orbital frontal cortex are
      still present at 2-year follow-up.

PMID- 24125066
TI  - Steric control of site selectivity in the Pd-catalyzed C-H acetoxylation of
      simple arenes.
AB  - This report describes the use of an oxidant and a ligand to control site
      selectivity in the Pd(OAc)2-catalyzed C-H acetoxylation of simple arenes. The use
      of MesI(OAc)2 as the terminal oxidant in combination with acridine as the ligand
      results in primarily sterically controlled selectivity. In contrast, with
      Pd(OAc)2 as the catalyst and PhI(OAc)2 as the oxidant, electronic effects
      dominate the selectivity of arene C-H acetoxylation. 

PMID- 24125067
TI  - Layered stigma among health-care and social service providers toward key affected
      populations in Jamaica and The Bahamas.
AB  - While considerable research has documented stigma toward key populations affected
      by HIV and AIDS - men who have sex with men (MSM), sex workers (SWs) - it
      provided limited empirical evidence on the presence of layered stigma among
      health-care professionals providing services for these populations. C-Change
      conducted a survey among 332 staff of health-care and social service agencies in
      Jamaica and The Bahamas to understand the levels of stigma toward people living
      with HIV (PLHIV), including MSM and SWs and factors associated with stigma. While
      most health-care professionals responding to the survey said that PLHIV, MSM, and
      SWs deserved quality care, they expressed high levels of blame and negative
      judgments, especially toward MSM and SWs. Across a stigma assessment involving
      eight vignette characters, the highest levels of stigma were expressed toward
      PLHIV who were also MSM or SWs, followed by PLHIV, MSM, and SWs. Differences were
      assessed by gender, country, type of staff, type of agency, and exposure to
      relevant training. Findings indicate higher reported stigma among nonclinical vs.
      clinical staff, staff who worked in general vs. MSM/SW-friendly health
      facilities, and among untrained vs. training staff. This implies the need for
      targeted staff capacity strengthening as well as improved facility environments
      that are MSM/SW-friendly. 

PMID- 24125068
TI  - Infliximab for autoimmune inner ear disease: case report and literature review.
AB  - OBJECTIVES: This study aimed (1) to report the long-term effects of infliximab, a
      murine monoclonal antibody directed against tumour necrosis factor-alpha, on
      autoimmune inner ear disease, and (2) to discuss dilemmas surrounding the long
      term management of autoimmune inner ear disease. CASE REPORT: A 49-year-old man
      presented with sudden-onset, left-sided, sensorineural hearing loss, tinnitus and
      vertigo. He was prescribed oral prednisolone, with benefit. Over several
      subsequent months, he experienced frequent relapses and progressive deterioration
      of high-frequency hearing bilaterally. Multiple agents failed to stabilise his
      condition. Following infliximab treatment, there was a documented and sustained
      improvement in his hearing and tinnitus. He stopped the treatment after 46 weeks,
      with rapid relapse of his condition. His hearing recovered quickly again after
      recommencing infliximab. CONCLUSION: The benefits of prolonged infliximab use and
      potential side effects must be balanced against allowing the disease to take its
      course, with progressive deafness. Randomised controlled trials are required to
      assess infliximab's optimal duration of use, long-term efficacy and safety in the
      treatment of autoimmune inner ear disease.

PMID- 24125070
TI  - Value of the mitral valve resistance in evaluation of symptomatic patients with
      mild and moderate mitral stenosis--a dobutamine stress echocardiographic study.
AB  - BACKGROUND: Conventional stenosis indexes poorly reflect the major hemodynamic
      consequence of mitral stenosis (MS). Valve resistance (VR) is a physiologic
      expression of stenosis. OBJECTIVES: This study aimed to demonstrate whether the
      mitral valve resistance (MVR) and its changes, relate to restricted exercise
      capacity in patients with mild and moderate mitral stenosis. METHODS: Twenty-four
      patients with rheumatic mild-to-moderate MS underwent transthoracic
      echocardiographic study (resting and dobutamine stress echocardiography [DSE]),
      divided into two groups; group I: symptomatic (12 patients) and group II:
      asymptomatic (12 patients). Mitral valve area (MVA), mean transmitral diastolic
      pressure gradient (TMPG), cardiac output (CO), and MVR were measured in all
      patients at rest and at peak DSE. Changes (?) in MVA, TMPG, CO, and MVR were
      calculated. Data underwent statistical analysis. RESULTS: From resting to peak
      dobutamine infusion, the MVR significantly decreased from 111.4 +/- 28.2 to 83.6
      +/- 27.0 dynes sec/cm(5) in group II (P < 0.001). The increase in MVR in group I
      (13.8 +/- 10.3 dynes sec/cm(5)) compared with its reduction (-27.8 +/- 15.6 dynes
      sec/cm(5)) in group II were highly significant different (P < 0.001). A reduction
      in MVR by less than 21.5 dynes sec/cm(5) at peak dobutamine infusion reflect a
      cutoff value considered to detect the hemodynamic significance of mild-to
      moderate MS with a sensitivity of 92% and a specificity of 73%. CONCLUSION: The
      changes in the MVR can be used as a DSE parameter for expression of stenosis
      severity and to describe discrepancy in symptom status in patients with mild-to
      moderate mitral stenosis.

PMID- 24125069
TI  - Histone acetyltransferase Hbo1 destabilizes estrogen receptor alpha by
      ubiquitination and modulates proliferation of breast cancers.
AB  - The estrogen receptor (ER) is a key molecule for growth of breast cancers. It has
      been a successful target for treatment of breast cancers. Elucidation of the ER
      expression mechanism is of importance for designing therapeutics for ER-positive
      breast cancers. However, the detailed mechanism of ER stability is still unclear.
      Here, we report that histone acetyltransferase Hbo1 promotes destabilization of
      estrogen receptor alpha (ERalpha) in breast cancers through lysine 48-linked
      ubiquitination. The acetyltransferase activity of Hbo1 is linked to its activity
      for ERalpha ubiquitination. Depletion of Hbo1 and anti-estrogen treatment
      displayed a potent growth suppression of breast cancer cell line. Hbo1 modulated
      transcription by ERalpha. Mutually exclusive expression of Hbo1 and ERalpha was
      observed in roughly half of the human breast tumors examined in the present
      study. Modulation of ER stability by Hbo1 in breast cancers may provide a novel
      therapeutic possibility. 

PMID- 24125071
TI  - A kinetic analysis of cadmium accumulation in a Cd hyper-accumulator fern,
      Athyrium yokoscense and tobacco plants.
AB  - Cadmium (Cd) accumulations in a Cd hyper-accumulator fern, Athyrium yokoscense
      (Ay), and tobacco, Nicotiana tabacum (Nt), were kinetically analysed using the
      positron-emitting tracer imaging system under two medium conditions (basal and no
      nutrient). In Ay, maximumly 50% and 15% of the total Cd accumulated in the distal
      roots and the shoots under the basal condition, respectively. Interestingly, a
      portion of the Cd in the distal roots returned to the medium. In comparison with
      Ay, a little fewer Cd accumulations in the distal roots and clearly higher Cd
      migration to the shoots were observed in Nt under the basal condition (maximumly
      40% and 70% of the total Cd, respectively). The no-nutrient condition down
      regulated the Cd migration in both species, although the regulation was highly
      stricter in Ay than in Nt (almost no migration in Ay and around 20% migration in
      Nt). In addition, the present work enabled to estimate physical and physiological
      Cd accumulation capacities in the distal roots, and demonstrated condition
      dependent changes especially in Ay. These results clearly suggested occurrences
      of species-/condition-specific regulations in each observed parts. It is probable
      that integration of these properties govern the specific Cd
      tolerance/accumulation in Ay and Nt. 

PMID- 24125072
TI  - An ultrasensitive nanowire-transistor biosensor for detecting dopamine release
      from living PC12 cells under hypoxic stimulation.
AB  - Dopamine (DA) is an important neurotransmitter that is involved in neuronal
      signal transduction and several critical illnesses. However, the concentration of
      DA is extremely low in patients and is difficult to detect using existing
      electrochemical biosensors with detection limits typically around nanomolar
      levels (~10(-9) M). Here, we developed a nanoelectronic device as a biosensor for
      ultrasensitive and selective DA detection by modifying DNA-aptamers on a multiple
      parallel-connected (MPC) silicon nanowire field-effect transistor (referred to as
      MPC aptamer/SiNW-FET). Compared with conventional electrochemical methods, the
      MPC aptamer/SiNW-FET has been demonstrated to improve the limit of DA detection
      to <10(-11) M and to possess a detection specificity that is able to distinguish
      DA from other chemical analogues, such as ascorbic acid, catechol,
      phenethylamine, tyrosine, epinephrine, and norepinephrine. This MPC aptamer/SiNW
      FET was also applied to monitor DA release under hypoxic stimulation from living
      PC12 cells. The real-time recording of the exocytotic DA induced by hypoxia
      reveals that the increase in intracellular Ca(2+) that is required to trigger DA
      secretion is dominated by an extracellular Ca(2+) influx, rather than the release
      of intracellular Ca(2+) stores. 

PMID- 24125073
TI  - Primary cutaneous amyloidosis of the glans penis. Two case reports and a review
      of the literature.
AB  - BACKGROUND: Primary cutaneous amyloidosis of the penis is a rare entity.
      OBJECTIVES: We describe two cases of primary penile cutaneous amyloidosis
      presenting as localized lesions on the penis and not associated with systemic
      amyloidosis. METHODS: A comprehensive literature review of all published cases.
      RESULTS: The rarest form of cutaneous amyloidosis, nodular amyloidosis, is the
      most frequent presentation of penis-limited cutaneous amyloid with a low
      incidence of systemic disease progression. CONCLUSIONS: Although primary nodular
      amyloidosis is a rare entity it seems to be the most frequent presentation of
      penile-limited cutaneous disease, with a low incidence of systemic involvement.

PMID- 24125074
TI  - Biobased thermosetting epoxy: present and future.

PMID- 24125075
TI  - Incremental filling technique and composite material--part II: shrinkage and
      shrinkage stresses.
AB  - OBJECTIVES: Finite element analysis (FEA) was used to study polymerization
      shrinkage stress in molars restored with composites and to correlate those
      stresses with experimentally measured tooth deformation. METHODS: Three
      composites (Filtek LS, Aelite LS Posterior, Filtek Supreme) and three filling
      techniques (bulk, 2.0-mm increments, and 1.0-mm increments) for restoring a molar
      were simulated in a two-dimensional FEA. Polymerization shrinkage was modeled
      using post-gel shrinkage, which was measured using the strain gauge technique
      (n=10). Cuspal tooth deformation, measured at the buccal and lingual surfaces
      with strain gauges in a laboratory study, was used to validate the analysis.
      Residual shrinkage stresses were expressed in modified von Mises equivalent
      stresses. Linear Pearson correlations were determined between the laboratory and
      FEA results. RESULTS: Post-gel shrinkage values (in volume %) were: Filtek LS
      (0.11 +/- 0.03) < Aelite LS Posterior (0.51 +/- 0.02) < Filtek Supreme (0.62 +/-
      0.09). The 1.0-mm increment filling caused substantially higher stresses and
      strains in the cervical enamel region. Significant correlations were found
      between: elastic modulus and FEA strain, elastic modulus and FEA stress, post-gel
      shrinkage and FEA strain, post-gel shrinkage and FEA stress, FEA strain and
      cuspal deformation by strain gauge, and FEA stress and cuspal deformation by
      strain gauge (p<0.05). CONCLUSIONS: Increasing the number of increments and high
      post-gel shrinkage and/or elastic modulus values caused higher stresses in the
      remaining tooth structure and tooth/restoration interface. Cuspal deformation
      measured with the strain gauge method validated the finite element analyses.

PMID- 24125076
TI  - Prevalence and molecular characterisation of Eimeria species in Ethiopian village
      chickens.
AB  - BACKGROUND: Coccidiosis, caused by species of the apicomplexan parasite Eimeria,
      is a major disease of chickens. Eimeria species are present world-wide, and are
      ubiquitous under intensive farming methods. However, prevalence of Eimeria
      species is not uniform across production systems. In developing countries such as
      Ethiopia, a high proportion of chicken production occurs on rural smallholdings
      (i.e. 'village chicken production') where infectious diseases constrain
      productivity and surveillance is low. Coccidiosis is reported to be prevalent in
      these areas. However, a reliance on oocyst morphology to determine the infecting
      species may impede accurate diagnosis. Here, we used cross-sectional and
      longitudinal studies to investigate the prevalence of Eimeria oocyst shedding at
      two rural sites in the Ethiopian highlands. RESULTS: Faecal samples were
      collected from 767 randomly selected chickens in May or October 2011. In
      addition, 110 chickens were sampled in both May and October. Eimeria oocysts were
      detected microscopically in 427 (56%, 95% confidence interval (95% CI) 52-59%) of
      the 767 faecal samples tested. Moderate clustering of positive birds was detected
      within households, perhaps suggesting common risk factors or exposure pathways.
      Seven species of Eimeria were detected by real time PCR in a subset of samples
      further analysed, with the prevalence of some species varying by region. Co
      infections were common; 64% (23/36, 95% CI 46-79%) of positive samples contained
      more than one Eimeria spp. Despite frequent infection and co-infection overt
      clinical disease was not reported. Eimeria oocysts were detected significantly
      more frequently in October (248/384, 65%, 95% CI 60-69%), following the main
      rainy season, compared to May (179/383, 47%, 95% CI 42-52%, p < 0.001). Eimeria
      oocyst positivity in May did not significantly affect the likelihood of detecting
      Eimeria oocyst five months later perhaps suggesting infection with different
      species or immunologically distinct strains. CONCLUSIONS: Eimeria spp oocysts may
      be frequently detected in faecal samples from village chickens in Ethiopia. Co
      infection with multiple Eimeria spp was common and almost half of Eimeria
      positive birds had at least one highly pathogenic species detected. Despite this,
      all sampled birds were free of overt disease. Although there was no evidence of a
      difference in the prevalence of oocysts in faecal samples between study regions,
      there was evidence of variation in the prevalence of some species, perhaps
      suggesting regional differences in exposure to risk factors associated with the
      birds, their management and/or location-specific environmental and ecological
      factors.

PMID- 24125079
TI  - The effect of Wolbachia on the lifetime reproductive success of its insect host
      in the field.
AB  - Wolbachia is a widespread endosymbiont that induces dramatic manipulations of its
      host's reproduction. Although there has been substantial progress in the
      developing theory for Wolbachia-host interactions and in measuring the effects of
      Wolbachia on host fitness in the laboratory, there is a widely recognized need to
      quantify the effects of Wolbachia on the host fitness in the field. The wasp
      Anagrus sophiae, an egg parasitoid of planthoppers, carries a Wolbachia strain
      that induces parthenogenesis, but its effects on the fitness of its Anagrus host
      are unknown. We developed a method to estimate the realized lifetime reproductive
      success of female wasps by collecting them soon after they die naturally in the
      field, counting the number of eggs remaining in their ovaries and quantifying
      Wolbachia density in their body. We sampled from a highly infected A. sophiae
      population and found no evidence for Wolbachia virulence and possible evidence
      for positive effects of Wolbachia on realized reproductive success. 

PMID- 24125080
TI  - A new flea, Ectinorus (Ectinorus) insignis n. sp. (Siphonaptera,
      Rhopalopsyllidae, Parapsyllinae), with notes on the subgenus Ectinorus in Chile
      and comments on unciform sclerotization in the superfamily Malacopsylloidea.
AB  - A list is provided for the species of Ectinorus sensu stricto from Chile.
      Ectinorus (Ectinorus) insignis n. sp. is described from Chile: this species is
      characterized by the male genitalia. In the subgenus Ectinorus, the authors
      report the presence in Chile of E. pilosus Beaucournu & Carmen Castro, 2002
      described from Argentina and E. simonsi (Rothschild, 1904) described from Bolivia
      but also known from Peru. A female neallotype is designated for E. ineptus
      Johnson, 1957. "Unciform sclerotization" is noted and illustrated for the first
      time, in all Malacopsylloidea, and a list is given for all studied species.

PMID- 24125077
TI  - Genome-wide analysis of condensin binding in Caenorhabditis elegans.
AB  - BACKGROUND: Condensins are multi-subunit protein complexes that are essential for
      chromosome condensation during mitosis and meiosis, and play key roles in
      transcription regulation during interphase. Metazoans contain two condensins, I
      and II, which perform different functions and localize to different chromosomal
      regions. Caenorhabditis elegans contains a third condensin, I(DC), that is
      targeted to and represses transcription of the X chromosome for dosage
      compensation. RESULTS: To understand condensin binding and function, we performed
      ChIP-seq analysis of C. elegans condensins in mixed developmental stage embryos,
      which contain predominantly interphase nuclei. Condensins bind to a subset of
      active promoters, tRNA genes and putative enhancers. Expression analysis in kle-2
      mutant larvae suggests that the primary effect of condensin II on transcription
      is repression. A DNA sequence motif, GCGC, is enriched at condensin II binding
      sites. A sequence extension of this core motif, AGGG, creates the condensin IDC
      motif. In addition to differences in recruitment that result in X-enrichment of
      condensin I(DC) and condensin II binding to all chromosomes, we provide evidence
      for a shared recruitment mechanism, as condensin I(DC) recruiter SDC-2 also
      recruits condensin II to the condensin I(DC) recruitment sites on the X. In
      addition, we found that condensin sites overlap extensively with the cohesin
      loader SCC-2, and that SDC-2 also recruits SCC-2 to the condensin I(DC)
      recruitment sites. CONCLUSIONS: Our results provide the first genome-wide view of
      metazoan condensin II binding in interphase, define putative recruitment motifs,
      and illustrate shared loading mechanisms for condensin I(DC) and condensin II.

PMID- 24125081
TI  - Structural and functional characterization of the MERIT40 to understand its role
      in DNA repair.
AB  - MERIT40 (MEdiator of RAP80 Interaction and Targeting 40) is a novel associate of
      the BRCA1-complex and plays an essential role in DNA damage repair. It is the
      least characterized protein of BRCA1-complex and mainly responsible for
      maintaining the complex integrity. However, its structural and functional aspects
      of regulating the complex stability still remain elusive. Here, we carried out a
      comprehensive examination of MERIT40 biophysical properties and identified its
      novel interacting partner which would help to understand its role in BRCA1
      complex. The recombinant protein was purified by affinity chromatography and
      unfolding pathway was determined using spectroscopic and calorimetric methods.
      Molecular model was generated using combinatorial approaches of modeling, and
      monomer-monomer docking was carried out to identify dimeric interface. Disordered
      region of MERIT40 was hatchet using trypsin and chymotrypsin to illustrate the
      existence of stable domain whose function was speculated through DALI search. Our
      findings suggest that MERIT40 forms a dimer in a concentration-independent
      manner. Its central region shows remarkable stability towards the protease
      digestion and has structural similarity with vWA-like region, a domain mainly
      present in complement activation factors. MERIT40 undergoes a three-state
      unfolding transition pathway with a dimeric intermediate. It interacts with
      adaptor molecule of BRCA1-complex, called ABRAXAS, thus help in extending the
      bridging interaction among various members which further stabilizes the whole
      complex. The results presented in this paper provide first-hand information on
      structural and folding behavior of MERIT40. These findings will help in
      elucidating the role of protein-protein interactions in stabilization of BRCA1
      complex. 

PMID- 24125082
TI  - The seven pillars of quality care in a statewide pediatric sexual assault nurse
      examiner program.
AB  - This article describes a systematic approach used by a statewide pediatric sexual
      assault nurse examiner program to ensure the quality of forensic medical
      examinations it provides in child sexual abuse investigations. Seven strategies
      for enhancing quality are described: (a) hiring experienced professionals, (b)
      effective training, (c) comprehensive protocols, (d) ample support for pediatric
      sexual assault nurses, (e) management oversight, (f) a clinical coordinator to
      provide ongoing training and technical assistance, and (g) a quality assurance
      process in which expert child abuse pediatricians review each statewide pediatric
      sexual assault nurse examination. To show the evolution of quality care over
      time, the program's experience from 2004 to 2010 is reviewed, and quality
      assurance data are analyzed. 

PMID- 24125083
TI  - A short form of the trauma symptom checklist for young children.
AB  - A short form of the Trauma Symptom Checklist for Young Children was derived from
      the original 90 items. An exploratory factor analysis of each factor identified
      the four items from each of the original factors with the highest eigenvalues.
      These items were subjected to confirmatory factor analysis. The best fit was
      obtained for an 8-factor, 32-item model. The short form evidenced good convergent
      validity with parent ratings obtained from the Child Behavior Checklist, the
      Child Sexual Behavior Inventory, and the University of California at Los Angeles
      Post-traumatic Stress Disorder Reaction Index (UCLA PTSD RI). Norms (t-scores and
      percentiles based on raw scores) were calculated by age and by gender. The short
      form has promise as a screening measure with parents in settings like a child
      advocacy center. 

PMID- 24125084
TI  - Voices of healing and recovery from childhood sexual abuse.
AB  - Child sexual abuse continues to occur for a significant number of children, often
      having deleterious consequences for survivors' physical and mental health.
      Research has thoroughly explored various consequences as a result of child sexual
      abuse, but scholars and practitioners know less about the healing processes from
      survivors' viewpoints. Using a constructivist grounded theory design, this study
      examined perceptions of healing in 10 female survivors of child sexual abuse.
      Results conclude with a theoretical model of healing, capturing the significance
      of supportive relationships, internal characteristics, turning points, and
      sources of active healing. Important sources of active healing include therapy,
      informal and formal education, compassion and empathy, blame attribution to
      abusers, and confronting abusers. Limitations and implications for research and
      practice are discussed. 

PMID- 24125085
TI  - Predictors of attrition from an expressive writing intervention for sexual abuse
      survivors.
AB  - This study examined predictors of attrition from a clinical trial examining the
      effects of an expressive writing intervention for sexual problems among female
      survivors of child sexual abuse. Participants were 124 women all reporting sexual
      difficulties, who were randomized to a trauma-focused condition (n = 45), an
      experimental sexual schema-focused condition (n = 37), or a control condition (n
      = 42). Thirty-five women (28%) dropped out before completing posttreatment
      assessments. Younger age, less education, and increased use of positive coping
      strategies were each independently associated with dropout. Results have
      implications for both researchers and clinicians working with this population,
      and it is hoped that these data can help bolster retention of those who are more
      likely to discontinue treatment.

PMID- 24125086
TI  - Is it love or sexual abuse? Young adults' perceptions of statutory rape.
AB  - Adults under age 25 comprise the majority of statutory rape perpetrators, yet we
      know little about their perceptions of statutory relationships. We assessed 210
      (50% male) young adults' perceptions of statutory rape involving a 15-year-old
      female adolescent and a male who was either 2, 4, or 6 years older. Across all
      age gaps, 73.7% of participants felt the relationship should not be a crime.
      Participants who read about a 4- or 6-year (versus 2-year) age gap perceived the
      relationship as significantly more of a crime and the older partner as more
      responsible and in need of legal intervention. Effects were partially mediated by
      perceptions of the relationship as exploitive. Results suggest a need to educate
      young adults about statutory rape. 

PMID- 24125087
TI  - Sexual revictimization: double betrayal and the risk associated with dissociative
      amnesia.
AB  - This study aimed to identify new treatment targets in order to develop more
      empirically informed initiatives to prevent sexual revictimization. A
      retrospective Web-based survey employing a mixed-methods design attracted a self
      selecting sample of 481 community respondents, 183 of whom indicated a history of
      childhood sexual abuse. Seventy-four percent were females whose ages ranged from
      16 to 69 years (mean = 31.2 years). Betrayal trauma referred to CSA committed by
      a trusted perpetrator (often caregivers). Disclosure experiences in childhood
      were reported though open-dialogue boxes. Double betrayal referred to high
      betrayal trauma being combined with a negative response to a disclosure. This was
      associated with both higher incidences of prior psychogenic amnesia for CSA and
      sexual revictimization in later life. The findings have implications for
      educating the guardians of children about the prevalence and implications of CSA
      as well as the importance of early recognition and appropriate responding. 

PMID- 24125088
TI  - Temperature-dependent, nitrogen-perturbed line shape measurements in the nu1 +
      nu3 band of acetylene using a diode laser referenced to a frequency comb.
AB  - The P(11) line of the nu1 + nu3 combination band of C2H2 was studied using an
      extended cavity diode laser locked to a frequency comb. Line shapes were measured
      for acetylene and nitrogen gas mixtures at a series of temperatures between 125
      and 296 K and total pressures up to 1 atm. The data were fit to two speed
      dependent line shape models and the results were compared. Line shape parameters
      were determined by simultaneously fitting data for all temperatures and pressures
      in a single multispectrum analysis. Earlier pure acetylene measurements [Cich et
      al. Appl. Phys. B 2012, 109, 373-38] were incorporated to account for self
      perturbation. The resulting parameters reproduce the observed line shapes for the
      acetylene-nitrogen system over the range of temperatures and pressures studied
      with average root-mean-square observed-calculated errors of individual line
      measurement fits of approximately 0.01% of maximum transmission, close to the
      experimental signal-to-noise ratios. Errors in the pressure measurements
      constitute the major systematic errors in these measurements, and a statistical
      method is developed to quantify their effects on the line shape parameters for
      the present system. 

PMID- 24125089
TI  - Light-emitting diode spectral sensitivity relationship with reproductive
      parameters and ovarian maturation in yellowtail damselfish, Chrysiptera parasema.
AB  - The present study investigated the effects of exposure to different light spectra
      and intensities on ovarian maturation in yellowtail damselfish, Chrysiptera
      parasema over a 4-months period. We used a white fluorescent bulb and three
      different light-emitting diodes (LEDs: red, peak at 630nm; green, 530nm; blue,
      450nm), at three different intensities each (0.3, 0.6, and 0.9W/m(2)). The
      effects of different illuminations were assessed by measuring the mRNA and
      protein expressions of vitellogenin (VTG) and estrogen receptor (ER),
      gonadosomatic index (GSI), and plasma estradiol-17beta (E2) hormone level. For
      green and blue lights, significantly higher levels of VTG and ER expressions,
      GSI, and plasma E2 were obtained, compared to the other light spectra.
      Histological analysis revealed the presence of vitellogenic oocytes in fish
      exposed to short wavelengths (green and blue) light. In addition, we observed
      significantly greater ovarian maturation in fish exposed to low and medium light
      intensities. The results indicate that exposure to green low intensity lighting
      accelerates gonadal maturation, and is likely to facilitate development of more
      energy-efficient aquaculture procedures. 

PMID- 24125090
TI  - Acute myocardial infarction triggered by bee sting: an alternative view.

PMID- 24125092
TI  - Highly reversible Li storage in hybrid NiO/Ni/graphene nanocomposites prepared by
      an electrical wire explosion process.
AB  - NiO/Ni/graphene nanocomposites were prepared using a simple and environmentally
      friendly method comprising an electrical wire pulse technique in oleic acid
      containing graphenes and subsequent annealing to form anodes for Li ion
      batteries. The control product of NiO/Ni nanocomposite was prepared under the
      same conditions and characterized by structural and electrochemical analysis. The
      obtained NiO/Ni/graphene nanocomposite particles had sizes of 5-12 nm and a high
      surface area of 137 m(2) g(-1). In comparison to NiO/Ni, NiO/Ni/graphene
      exhibited improved cycling performance and good rate capability. Reversible
      capacity was maintained at over 600 mA h g(-1) at 0.2 C and was attributed to the
      alleviation in volume change and improved electrical conductivity of
      NiO/Ni/graphene nanocomposites. 

PMID- 24125091
TI  - Aortic valve replacement after previous heart surgery in high-risk patients:
      transapical aortic valve implantation versus conventional aortic valve
      replacement-a risk-adjusted and propensity score-based analysis.
AB  - OBJECTIVE: Cardiac reoperations have been associated with increased morbidity and
      mortality compared with first-time surgery. We analyzed our experience with
      reoperative aortic valve replacement (redo-AVR) and compared these results with
      those from patients who had undergone transapical aortic valve implantation (TA
      AVI) as a second heart operation. METHODS: In the present retrospective
      observational comparative study, we analyzed the outcome of 136 patients with
      previous cardiac surgery who had undergone conventional redo-AVR (n = 59; since
      2006) or TA-AVI (n = 77; since 2008) with respect to the 30-day outcomes (Valve
      Academic Research Consortium criteria), 1- and 3-year survival, and the risk
      factors for both approaches after previous heart surgery. RESULTS: Neither group
      differed significantly in their risk profile, leading to similar Society of
      Thoracic Surgeon score and EuroSCORE. The 30-day mortality was 3.39% (n = 2) in
      the redo-AVR group and 7.8% (n = 6) in the redo TA-AVI group (P = .465). The
      overall combined safety endpoint at 30 days was significantly lower for the TA
      AVI patients (18.1% vs 33.9% in redo-AVR; P = .036). The unadjusted and adjusted
      1-year survival showed no difference between the 2 groups. The unadjusted 3-year
      survival revealed a 2.1-fold greater mortality risk after TA-AVI (P = .055).
      Adjustment by multivariate Cox regression analysis (hazard ratio, 1.427; 95%
      confidence interval, 0.635-3.209; P = .389) and propensity score (hazard ratio,
      1.571; 95% confidence interval, 0.575-4.291; P = .378) led to a >50% risk
      reduction, resulting in similar 3-year survival in the 2 groups. CONCLUSIONS:
      Redo-AVR can be performed with acceptable results in high-risk patients and still
      serves as the reference standard. Reoperative valve surgery by TA-AVI is feasible
      and results in comparable short- and mid-term survival.

PMID- 24125093
TI  - Disseminated rhinosporidiosis.
AB  - INTRODUCTION: Rhinosporidiosis primarily affects the mucous membranes of the nose
      and nasopharynx. The disseminated form of this chronic fungal disease is
      extremely rare. CASE REPORT: The authors present a case of disseminated
      rhinosporidiosis in an immunocompetent patient with involvement of the skin,
      subcutaneous tissue, muscle, bone, penis and urethra, and with a long-standing
      primary lesion in the nose. DISCUSSION: A late or atypical presentation of
      rhinosporidiosis may cause diagnostic dilemma. Fine needle aspiration cytology of
      the tumoural lesions may establish the diagnosis. Histopathology is confirmatory.
      The subcutaneous masses may be solid or cystic. Ulceroproliferative lesions need
      to be differentiated from malignancies. CONCLUSION: This is the first reported
      case of truly disseminated rhinosporidiosis with simultaneous involvement of
      multiple anatomically unrelated sites in a single patient. This is also the first
      reported case of cystic rhinosporidiosis. The possibility and sequelae of
      spontaneous regression of rhinosporidiosis are also discussed.

PMID- 24125094
TI  - Nicotelline: a proposed biomarker and environmental tracer for particulate matter
      derived from tobacco smoke.
AB  - Particulate matter (PM) derived from tobacco smoke contains numerous toxic
      substances. Since the PM and gas phase of tobacco smoke may distribute
      differently in the environment and substances in them may have different human
      bioavailability, multiple tracers and biomarkers for tobacco smoke constituents
      are desirable. Nicotelline is a relatively nonvolatile alkaloid present in
      tobacco smoke, and therefore, it has the potential to be a suitable tracer and
      biomarker for tobacco smoke-derived PM. We describe experiments demonstrating
      that nicotelline is present almost entirely in the PM, in both freshly generated
      cigarette smoke and aged cigarette smoke. An excellent correlation between the
      mass of nicotelline and the mass of the PM in aged cigarette smoke was found. We
      also describe experiments suggesting that the main source of nicotelline in
      tobacco smoke is dehydrogenation of another little-studied tobacco alkaloid,
      anatalline, during the burning process. We show that nicotelline metabolites can
      be measured in the urine of smokers and that nicotelline can be measured in house
      dust from homes of smokers and nonsmokers. We conclude that nicotelline should be
      useful as a tracer and biomarker for PM derived from tobacco smoke. 

PMID- 24125095
TI  - Exclusive breastfeeding practices in relation to social and health determinants:
      a comparison of the 2006 and 2011 Nepal Demographic and Health Surveys.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) for the first six months can have a
      significant impact on reducing child morbidity and mortality rates. The objective
      of this study was to compare the determinants of and trends in EBF in infants <=
      5 months from the 2006 and 2011 Nepal Demographic and Health Surveys. METHODS:
      Data on mother/infant pairs having infants of <= 5 months from 2006 (n = 482) and
      2011 (n = 227) were analysed. The EBF rate, determinants of EBF, and changes in
      EBF rates between the 2006 and 2011 surveys were examined using Chi-square test
      and multiple logistic regression. RESULTS: The EBF rate for <= 5 months in 2006
      was 53.2% (95% CI, 47.1%-59.3%) and 66.3% (95% CI, 56.6%-74.8%) in 2011. In 2006,
      infants <= 4 months were more likely to be EBF [(aOR) 3.086, 95% CI (1.825
      5.206)] after controlling for other factors. A geographic effect was also found
      in this study, with the odds of EBF higher for infants from the Hills [aOR 3.426,
      95% CI (1.568-7.474)] compared to those form the mountains. The odds of EBF were
      also higher for higher order infants [aOR 1.968, 95% CI (1.020-3.799)]. Infants
      whose fathers belonged to non-agricultural occupation were less likely to be
      provided with EBF. Infants who were delivered in the home were more likely to
      experience EBF [aOR 1.886; 95% CI (1.044-3.407)]. In 2011, infants of age <= 4
      months were more likely [aOR 4.963, 95% CI (2.317-10.629)] to have been breastfed
      exclusively. While there was an increase in the EBF rate between 2006 and 2011
      surveys, the significant increase was noticed only among the infants of four
      months [32.0%; 95% CI (19.9%-47.0%)] in 2006 to [65.5%; 95% CI (48.1-79.6)] in
      2011. CONCLUSIONS: The proportion of infants who were EBF was higher in Nepal in
      2011survey compared to 2006 survey; however, this is still below the recommended
      WHO target of 90%. Infant's age, ecological region, parity and father's
      occupation were associated with EBF. Further interventions such as peer
      counselling, antenatal counselling and involving fathers in the community to
      promote EBF in Nepal are recommended.

PMID- 24125096
TI  - Spin-crossover modification through selective CO2 sorption.
AB  - We present a spin-crossover Fe(II) coordination polymer with no permanent
      channels that selectively sorbs CO2 over N2. The one-dimensional chains display
      internal voids of ~9 A diameter, each being capable to accept one molecule of CO2
      at 1 bar and 273 K. X-ray diffraction provides direct structural evidence of the
      location of the gas molecules and reveals the formation of O?C?O(delta(-))...pi
      interactions. This physisorption modifies the spin transition, producing a 9 K
      increase in T1/2. 

PMID- 24125097
TI  - Do brief alcohol motivational interventions work like we think they do?
AB  - BACKGROUND: Questions remain about how brief motivational interventions (BMIs)
      for unhealthy alcohol use work, and addressing these questions may be important
      for improving their efficacy. Therefore, we assessed the effects of various
      characteristics of BMIs on drinking outcomes across 3 randomized controlled
      trials (RCTs). METHODS: Audio recordings of 314 BMIs were coded. We used the
      global rating scales of the Motivational Interviewing Skills Code (MISC) 2.1:
      counselor's acceptance, empathy, and motivational interviewing (MI) spirit, and
      patient's self-exploration were rated. MI proficiency was defined as counselor's
      rating scale scores >=5. We also used the structure, confrontation, and advice
      subscale scores of the Therapy Process Rating Scale and the Working Alliance
      Inventory. We examined these process characteristics in interventions across 1
      U.S. RCT of middle-aged medical inpatients with unhealthy alcohol use (n = 124)
      and 2 Swiss RCTs of young men with binge drinking in a nonclinical setting: Swiss
      one (n = 62) and Swiss-two (n = 128). We assessed the associations between these
      characteristics and drinks/d reported by participants 3 to 6 months after study
      entry. RESULTS: In all 3 RCTs, mean MISC counselor's rating scales scores were
      consistent with MI proficiency. In overdispersed Poisson regression models, most
      BMI characteristics were not significantly associated with drinks/d in follow-up.
      In the U.S. RCT, confrontation and self-exploration were associated with more
      drinking. Giving advice was significantly associated with less drinking in the
      Swiss-one RCT. Contrary to expectations, MI spirit was not consistently
      associated with drinking across studies. CONCLUSIONS: Across different
      populations and settings, intervention characteristics viewed as central to
      efficacious BMIs were neither robust nor consistent predictors of drinking
      outcome. Although there may be alternative reasons why the level of MI processes
      was not predictive of outcomes in these studies (limited variability in scores),
      efforts to understand what makes BMIs efficacious may require attention to
      factors beyond intervention process characteristics typically examined.

PMID- 24125098
TI  - Employing arynes in transition-metal-free monoarylation of aromatic tertiary
      amines.
AB  - The highly monoselective N-arylation of aromatic tertiary amines using a
      transition-metal-free approach using arynes has been developed. The reaction
      afforded functionalized diaryl amines in moderate to excellent yield. High levels
      of functional group compatibility especially with halogen containing substrates,
      dyes and donor-acceptor systems, and high yields of products are the notable
      features of the present reaction. 

PMID- 24125099
TI  - Severe dermatitis from Dermabond (r) surgical glue.

PMID- 24125101
TI  - No association found between CYP2D6 genotype and early breast cancer events in
      tamoxifen-treated patients.
AB  - BACKGROUND: CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several
      studies have investigated the relationship between the CYP2D6 genotype and
      tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use,
      aromatase inhibitor use, and chemotherapy may account for some of the
      discrepancies. We examined the association between CYP2D6 genotype and early
      breast cancer events in tamoxifen-treated breast cancer patients, in relation to
      CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. MATERIAL AND
      METHODS: Pre- and postoperative questionnaires on lifestyle and concomitant
      medications were completed by 634 primary breast cancer patients between 2002 and
      2008, among whom 333 patients had ER-positive tumors and received tamoxifen.
      CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data,
      breast cancer events, and tumor characteristics was obtained from patients'
      charts, population registries, the Regional Tumor Registry, and pathology
      reports. RESULTS: Median follow-up was 4.9 years. Neither poor metabolizers
      (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR
      1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when
      compared with extensive metabolizers. CYP2D6 activity score (taking into account
      genotype and CYP2D6 inhibitor use) was not associated with early breast cancer
      events (LogRank, Ptrend = 0.44). CONCLUSIONS: CYP2D6 genotype was not associated
      with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase
      inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of
      minor importance for tamoxifen-treated patients in Scandinavia.

PMID- 24125102
TI  - Partnership status affects the association between gastrointestinal symptoms and
      quality of life after radiation therapy for prostate cancer.
AB  - PURPOSE: To study if partnership modifies the effect of gastrointestinal symptoms
      on quality of life after radiation therapy for prostate cancer. MATERIAL AND
      METHODS: Using a study-specific questionnaire we conducted a cross-sectional
      follow-up of the occurrence gastrointestinal symptoms and quality of life after
      radiation therapy for prostate cancer. We obtained information from 874 prostate
      cancer survivors treated with radiation therapy at the Sahlgrenska University
      Hospital, Sweden between 1994 and 2006. In this paper we describe how partnership
      status affects the association between gastrointestinal symptoms and quality of
      life. RESULTS: We found that unpartnered men with gastrointestinal symptoms
      reported a lower quality of life than unpartnered men without such symptoms.
      Unpartnered men with symptoms had an excess risk of low quality of life compared
      with unpartnered men without symptoms for those experiencing altered composition
      of stools, prevalence ratio 3.8 (95% CI 1.1-13.1), leakage, 3.6 (1.3-10.1),
      sensory bowel symptoms, 4.5 (1.6-12.8), and for urgency, 4.2 (1.2-15.1). We also
      found that unpartnered men with symptoms had an excess risk of low quality of
      life compared with partnered men with symptoms for those experiencing altered
      composition of stools, prevalence ratio 2.9 (95% CI 1.4-5.8), leakage 2.8 (1.2
      6.4), sensory bowel symptoms 3.4 (1.5-7.4), urgency 2.6 (1.2-5.8), and for any
      gastrointestinal symptom 2.5 (1.3-4.9). CONCLUSION: Unpartnered men may represent
      a group that is specifically vulnerable to the distressful effects of
      gastrointestinal symptoms after radiation therapy for prostate cancer.

PMID- 24125103
TI  - Modelling the cost-effectiveness of adjuvant lapatinib for early-stage breast
      cancer.
AB  - BACKGROUND: It has been shown in the NeoALTTO trial that a neoadjuvant regimen
      containing paclitaxel, lapatinib and trastuzumab is superior to regimens which
      include only one of the HER2 antagonists with paclitaxel. In light of these
      results, we modelled the potential cost-effectiveness of adjuvant lapatinib for
      patients with HER2-positive early-stage breast cancer. MATERIAL AND METHODS: We
      constructed a Markov state-transition model with three different health states:
      disease free, relapse, and death. We assumed an 18-week course of lapatinib was
      added to the TCH arm of the BCIRG 006 trial. Since no efficacy data are available
      for combining adjuvant lapatinib with trastuzumab, we ran the model assuming five
      different hypothetical hazard ratios for disease free survival when lapatinib is
      added to TCH (TCH was used as the control group). The hazard ratios were 0.9,
      0.8, 0.7, 0.6, and 0.5. Outcomes are given in quality-adjusted life-years
      (QALYs). Both costs and QALYs were discounted at the 4% rate. We calculated the
      cost per QALY from the perspective of the Irish health care system. Probabilistic
      sensitivity analysis and one-way sensitivity were performed and confidence
      intervals were bootstrapped. RESULTS: The incremental cost-effectiveness ratios
      (ICERs) for the five hazard ratios are ?53 089/QALY, ?27 893/QALY, ?18 463/QALY,
      ?13 527/QALY and ?10 490/QALY, respectively. Using the ?45 000/QALY threshold, an
      adjuvant lapatinib regimen is cost-effective at the 0.8 hazard ratio. Adjuvant
      lapatinib becomes cost-effective at the 0.879 hazard ratio where the ICER is ?44
      825/QALY. CONCLUSION: In the Irish setting, an adjuvant lapatinib regimen would
      be considered cost-effective for patients with HER2-positive early-stage breast
      cancer for four of the five hypothesised hazard ratios. Data from both adjuvant
      and neoadjuvant trials suggest that the hazard ratio required to achieve cost
      effectiveness for adjuvant lapatinib is both possible and plausible.

PMID- 24125104
TI  - Pulmonary hypertension, right ventricular function, and clinical outcome in acute
      decompensated heart failure.
AB  - BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction
      have been associated with adverse outcome in patients with chronic heart failure.
      However, data are lacking in the setting of acute decompensated heart failure
      (ADHF). We sought to determine prognostic significance of PH in patients with
      ADHF and its interaction with RV function. METHODS: We studied 326 patients with
      ADHF. Pulmonary artery systolic pressure (PASP) and RV function were determined
      with the use of Doppler echocardiography, with PH defined as PASP >50 mm Hg. The
      primary end point was all-cause mortality during 1-year follow-up. RESULTS: PH
      was present in 139 patients (42.6%) and RV dysfunction in 83 (25.5%). The
      majority of patients (70%) with RV dysfunction had PH. Compared with patients
      with normal RV function and without PH, the adjusted hazard ratio (HR) for
      mortality was 2.41 (95% confidence interval [CI] 1.44-4.03; P = .001) in patients
      with both RV dysfunction and PH. Patients with normal RV function and PH had an
      intermediate risk (adjusted HR 1.78, 95% CI 1.11-2.86; P = .016). Notably,
      patients with RV dysfunction without PH were not at increased risk for 1-year
      mortality (HR 1.04, 95% CI 0.43-2.41; P = .94). PH and RV function data resulted
      in a net reclassification improvement of 22.25% (95% CI 7.2%-37.8%; P = .004).
      CONCLUSIONS: PH and RV function provide incremental prognostic information in
      ADHF. The combination of PH and RV dysfunction is particularly ominous. Thus, the
      estimation of PASP may be warranted in the standard assessment of ADHF.

PMID- 24125105
TI  - Characteristics and outcomes of heart failure-related intensive care unit
      admissions in children with cardiomyopathy.
AB  - OBJECTIVE: The purpose of this study was to describe patient characteristics and
      outcomes of heart failure (HF)-related intensive care unit (ICU) hospitalizations
      in children with cardiomyopathy (CM). METHODS AND RESULTS: A query of the
      Pediatric Health Information System database, a large administrative and billing
      database of 43 tertiary children's hospitals, was performed. A total of 17,309 HF
      related ICU hospitalizations from 2005 to 2010 of 14,985 children <=18 years old
      were analyzed. Of those, 2,058 (12%) hospitalizations for CM-HF in 1,599 (11%)
      children were identified. Classification into CM subtypes was not possible owing
      to database limitations. The number of yearly CM-HF hospitalizations
      significantly increased during the study period (P = .036). Overall mortality was
      11%, and cardiac transplantation occurred in 20% of hospitalizations. Mechanical
      circulatory support (MCS) was used in 261 (13%) of hospitalizations. Renal
      failure, MCS, respiratory failure, sepsis, and vasoactive medications were
      associated with mortality on multivariable analysis. Significant comorbidities
      associated with these hospitalizations included arrhythmias in 42%, renal failure
      in 13%, cerebrovascular disease in 6%, and hepatic impairment in 5%. CONCLUSIONS:
      HF-related ICU hospitalizations in children with cardiomyopathy are increasing.
      These children are at high risk for poor outcomes with an in-hospital mortality
      of 11%.

PMID- 24125106
TI  - Gremlin-1 identifies fibrosis and predicts adverse outcome in patients with heart
      failure undergoing endomyocardial biopsy.
AB  - BACKGROUND: Gremlin-1 (Grem1), an antagonist of bone morphogenetic proteins, is
      involved in fibrotic tissue formation in kidney and lung. The impact of
      myocardial Grem1 expression is unknown. We investigated the prognostic value of
      Grem1 expression in 214 consecutive patients with nonischemic heart failure (HF)
      undergoing endomyocardial biopsy. METHODS: In all patients, the following risk
      factors were assessed: Grem1 expression (semiquantitative score scheme ranging
      from 1 to 4), presence of inflammatory markers, detection of viral genome, left
      ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter
      (LVEDD), New York Heart Association functional class (NYHA), troponin I, and B
      type natriuretic peptide. Degree of myocardial fibrosis was defined as an index.
      Study end point was a combination of all-cause death and HF-related
      rehospitalization within 3 years of follow-up. RESULTS: Grem1 expression
      significantly correlated with the degree of myocardial fibrosis (correlation
      coefficient r = 0.619; P < .0001). Patients with the highest Grem1 expression
      (score 4) showed the most severely impaired LVEF and highest LVEDD (P < .0001 and
      P = .030, respectively, for comparison of semiquantitative scores). During follow
      up, 33 patients (15.4%) reached the study end point. Grem1 expression and NYHA
      >=II were independent predictors of the end point (Grem1: hazard ratio [HR] 7.5,
      95% confidence interval [CI] 1.8-32.2; P = .006; NYHA >=II: HR 2.0, 95% CI 1.0
      4.1; P = .048). CONCLUSIONS: Grem1 correlates with the degree of myocardial
      fibrosis and left ventricular dysfunction and is an independent predictor of
      adverse outcome in patients with nonischemic HF.

PMID- 24125107
TI  - Differences in blood volume components between hyporesponders and responders to
      erythropoietin alfa: the heart failure with preserved ejection fraction (HFPEF)
      anemia trial.
AB  - BACKGROUND: Hyporesponders to erythropoietin-stimulating agents (ESAs) have been
      associated with an increased subsequent risk of death or cardiovascular events.
      We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would
      have higher plasma volumes and lower red cell deficits than subjects who are
      responsive to therapy. METHODS: As part of a prospective, single blind,
      randomized, placebo-controlled study comparing erythropoietin alfa with placebo
      in older adults (n = 56) with heart failure and a preserved ejection fraction
      (HFPEF), we performed blood volume analysis with the use of an indicator dilution
      technique with (131)iodine-labeled albumin. We evaluated differences in plasma
      volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in
      hemoglobin within the first 4 weeks of treatment with erythropoetin alfa)
      compared with subjects who were responders and controls. RESULTS: Nine of 28
      subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ
      from responders nor control subjects by any baseline demographic, clinical, or
      laboratory parameter, including hemoglobin. Hyporesponders had a greater total
      blood volume expansion (1,264.7 +/- 387 vs 229 +/- 206 mL; P = .02) but less of a
      red cell deficit (-96.2 +/- 126 vs -402.5 +/- 80.6 mL; P = .04) and a greater
      plasma volume expansion (+1,360.8 +/- 264.5 vs +601.1 +/- 165.5 mL; P = .01).
      Among responders, the increase in hemoglobin with erythropoietin alfa was
      associated primarily with increases in red cell volume (r = 0.91; P < .0001) as
      well as a decline in plasma volume (r = -0.55; P = .06). CONCLUSIONS: Among older
      adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a
      hemodilutional basis of their anemia, suggesting that blood volume analysis can
      identify a cohort likely to respond to therapy.

PMID- 24125108
TI  - Vitamin D in heart failure.
AB  - Evidence linking vitamin D to cardiovascular (CV) health has accumulated in
      recent years: numerous epidemiologic studies report deficiency as a significant
      CV risk factor, and rodent models suggest that active vitamin D can modulate
      critical remodeling processes, including cardiac hypertrophy and extracellular
      matrix remodeling. The presence of vitamin D signaling machinery within the human
      heart implies a direct role for this hormone in cardiac physiology and may
      explain associations between vitamin D status and CV outcomes. Heart failure (HF)
      represents a growing social and economic burden worldwide. Myocardial remodeling
      is central to HF development, and in the context of emerging evidence supporting
      mechanistic involvement of vitamin D, this review provides critical appraisal of
      scientific literature related to the role of vitamin D in CV disease, including
      data from epidemiologic and supplementation studies, as well as novel findings
      from animal models and in vitro work. Although associative data linking vitamin D
      and CV outcomes and evidence supporting a role for vitamin D in relevant
      pathogenic processes are both substantial, there are limited mechanistic data to
      indicate vitamin D supplementation as a viable therapeutic adjunct for the
      prevention of HF development following myocardial injury.

PMID- 24125110
TI  - CPAP and short-term mortality in acute cardiac pulmonary edema: now, what can we
      be expecting?

PMID- 24125111
TI  - Reply to short-term mortality and CPAP in acute cardiac pulmonary edema: how and
      what can we be expecting?

PMID- 24125109
TI  - Right ventricular afterload and the role of nitric oxide metabolism in left-sided
      heart failure.
AB  - Awareness has grown in recent years that right ventricular (RV) function is
      equally important as left ventricular (LV) function in the setting of left-sided
      heart disease. RV dysfunction can be the consequence of an increased afterload
      imposed by the failing LV. The concept of "afterload" is physically most
      correctly described by vascular input impedance. However, for clinical purposes,
      afterload is most often modeled to consist of 3 components; pulmonary vascular
      resistance (PVR), pulmonary arterial compliance (PAC), and characteristic
      impedance. Whereas PVR is historically most described, PAC (which represents the
      distensibility of the vasculature) has rapidly gained recognition for its
      prognostic ability in both pulmonary arterial hypertension and left-sided heart
      disease. Owing to the specific anatomy of the pulmonary circulation, PVR and PAC
      have an inverse hyperbolic relationship, which position can be shifted by varying
      wedge pressures. Knowledge of the afterload components helps one to understand
      how elevated left-sided filling pressures increase pulsatile load on the RV. An
      increase in resistive load (known as "reactive" or "out-of-proportion" pulmonary
      hypertension) ultimately complements the increase in pulsatile load.
      Perturbations in nitric oxide metabolism are thought to be crucial in this
      evolution and have therefore been sought as a major therapeutic target.

PMID- 24125112
TI  - A comparison investigation of DNP-binding effects to HSA and HTF by spectroscopic
      and molecular modeling techniques.
AB  - This paper describes the interaction between 2,4-dinitrophenol (DNP) with the two
      drug carrier proteins - human serum albumin (HSA) and human holo transferrin
      (HTF). Hence, binding characteristics of DNP to HSA and HTF were analyzed by
      spectroscopic and molecular modeling techniques. Based on results obtained from
      fluorescence spectroscopy, DNP had a strong ability to quench the intrinsic
      fluorescence of HSA and HTF through a static quenching procedure. The binding
      constant and the number of binding sites were calculated as 2.3 * 10(11) M(-1)
      and .98 for HSA, and 1.7 * 10(11) M(-1) and 1.06 for HTF, respectively. In
      addition, synchronous fluorescence results showed that the microenvironment of
      Trp had a slight tendency of increasing its hydrophobicity, whereas the
      microenvironment of the Tyr residues of HSA did not change and that of HTF showed
      a significant trend (red shift of about 4 nm) of an increase in polarity. The
      distance between donor and acceptor was obtained by the Forster energy according
      to fluorescence resonance energy transfer, and was found to be 3.99 and 3.72 nm
      for HSA and HTF, respectively. The critical induced aggregation concentration
      (CCIAC) of the drug on both proteins was determined and confirmed by an
      inflection point of the zeta potential behavior. Circular dichroism data revealed
      that the presence of DNP caused a decrease of the alpha-helical content of HSA
      and HTF, and induced a remarkable mild denaturation of both proteins. The
      molecular modeling data confirmed our experimental results. This study is deemed
      useful for determining drug dosage. 

PMID- 24125113
TI  - Nonresponders, partial responders, and complete responders to PDE5 inhibitors
      therapy according to IIEF criteria: validation of an anchor-based treatment
      responder classification.
AB  - INTRODUCTION: Despite widespread use of the International Index of Erectile
      Function (IIEF) in erectile dysfunction (ED) research, there are no published
      criteria for classifying ED treatment responders in clinical trials or patient
      management settings. A new classification for treatment response in men with ED
      has been developed and validated in a large clinical trial database. AIM: The
      study aims to test discriminant and convergent validity of the responder
      classification and examine the role of covariates. METHOD: Treatment assignment
      was used to test discriminant validity. The diary-based Sexual Encounter Profile
      (SEP) question ("Did your erection last long enough for you to have successful
      intercourse?") and Global Assessment Question (GAQ) ("Has the treatment you have
      been taking over the past study interval improved your erections?") were used to
      evaluate convergent validity. Chi-square and Cochran-Armitage trend tests were
      used to examine outcome associations. Logistic regression was used to further
      assess the relationship of outcomes controlling for covariates. MAIN OUTCOME
      MEASURE: The classification measure was developed and validated in a database
      from 17 clinical trials in 3,252 men with ED randomized to placebo or tadalafil.
      The treatment responder is defined as complete (erectile function [EF] >= 26);
      partial (EF < 26; met minimal clinically important difference [MCID] criteria);
      or nonresponder following treatment (EF < 26; did not meet MCID). RESULTS: The
      new responder definition performed consistently well in all prespecified tests of
      validity. Eighty-nine percent of subjects classified as complete responders were
      in the treatment group, and the responder definition was associated with changes
      on the SEP and GAQ measures, respectively (SEP odds ratio [OR] = 14, 95%
      confidence intervals [CI] 11-17; GAQ OR = 50, 95% CI 39-88; complete vs.
      nonresponders). CONCLUSIONS: We developed and validated a novel method of
      defining an ED treatment responder based on multiple IIEF criteria and using
      other measures (SEP, GAQ) for validation. The results have implications for
      understanding results of clinical trials in ED, and in monitoring response to
      treatment in the clinic.

PMID- 24125114
TI  - Is acting on delusions autonomous?
AB  - In this paper the question of autonomy in delusional disorders is investigated
      using a phenomenological approach. I refer to the distinction between freedom of
      intentional action, and freedom of the will, and develop phenomenological
      descriptions of lived autonomy, taking into account the distinction between a pre
      reflective and a reflective type. Drawing on a case report, I deliver finely
      grained phenomenological descriptions of lived autonomy and experienced self
      determination when acting on delusions. This analysis seeks to demonstrate that a
      person with delusions can be described as responsible for her behaviour on a
      'framed' level (level of freedom of intentional action), even though she is not
      autonomous on a higher ('framing') level (level of freedom of the will), if, and
      only if, the goods of agency for herself and others are respected. In these cases
      the person with delusions is very nearly comparable to people in love, who are
      also not free to choose their convictions, and who could also be rightly held
      responsible for the behaviour flowing from their convictions. 

PMID- 24125116
TI  - Evolution of AgX nanowires into Ag derivative nano/microtubes for highly
      efficient visible-light photocatalysts.
AB  - Our study proposes a novel strategy for the synthesis of Ag derivatives (AgX@Ag
      (X = Cl and Br) or Ag nano/microtubes) using the controlled chemical reduction or
      electron-beam irradiation of AgX nanowires (NWs), which are formed from the
      controlled dewetting of a AgX thin film on colloidal particles. The size of the
      AgX@Ag and Ag nano/microtubes can be controlled using the AgCl NWs as templates
      and varying the concentration of NaX. By controlling the concentration of NaBr,
      heterojunction-structured AgCl/AgBr NWs (H-AgCl/AgBr NWs) can be produced from
      the AgCl NWs due to a partial ion-exchange reaction (low concentration), and the
      AgBr NWs produced after a complete ion-exchange reaction between Cl- and Br- are
      further grown into micrometer-sized AgBr wires (high concentration). The
      resulting AgX NWs can be transformed into corresponding AgX@Ag or Ag
      nano/microtubes via a controlled chemical or physical method. The AgX derivatives
      (AgX@Ag nanotubes (NTs) and AgX NWs) are tested as visible-light-induced
      photocatalysts for decomposition of methyl orange. The AgX@Ag NTs exhibit the
      best photocatalytic activities due to the advantages of the core@shell structure,
      allowing multiple reflections of visible light within the interior cavity,
      providing a well-defined and clean Ag/AgX interface, and preventing direct
      adsorption of pollutants on AgX because of the shell structure. These advantages
      allow AgX@Ag NTs to maintain high catalytic performance even after multiple uses.
      The approach can also be used as a direct method for preparing Ag nano/microtubes
      with a tailored size and as a new method for incorporating a AgX NW core into a
      Ag nano/microtube shell. Our approach is useful for synthesizing various types of
      one-dimensional heterostructured NWs or metal NTs with controlled structures and
      properties. 

PMID- 24125115
TI  - Kinetic characterization of high-activity mutants of human butyrylcholinesterase
      for the cocaine metabolite norcocaine.
AB  - It has been known that cocaine produces its toxic and physiological effects
      through not only cocaine itself, but also norcocaine formed from cocaine
      oxidation catalysed by microsomal CYP (cytochrome P450) 3A4 in the human liver.
      The catalytic parameters (kcat and Km) of human BChE (butyrylcholinesterase) and
      its three mutants (i.e. A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/E441D
      and A199S/F227A/S287G/A328W/Y332G) for norcocaine have been characterized in the
      present study for the first time and compared with those for cocaine. On the
      basis of the obtained kinetic data, wild-type human BChE has a significantly
      lower catalytic activity for norcocaine (kcat=2.8 min(-1), Km=15 MUM and
      kcat/Km=1.87 * 10(5) M(-1).min(-1)) compared with its catalytic activity for (-)
      cocaine. The BChE mutants examined in the present study have considerably
      improved catalytic activities against both cocaine and norcocaine compared with
      the wild-type enzyme. Within the enzymes examined in the present study, the
      A199S/F227A/S287G/A328W/Y332G mutant (CocH3) is identified as the most efficient
      enzyme for hydrolysing both cocaine and norcocaine. CocH3 has a 1080-fold
      improved catalytic efficiency for norcocaine (kcat=2610 min(-1), Km=13 MUM and
      kcat/Km=2.01 * 10(8) M(-1).min(-1)) and a 2020-fold improved catalytic efficiency
      for cocaine. It has been demonstrated that CocH3 as an exogenous enzyme can
      rapidly metabolize norcocaine, in addition to cocaine, in rats. Further kinetic
      modelling has suggested that CocH3 with an identical concentration with that of
      the endogenous BChE in human plasma can effectively eliminate both cocaine and
      norcocaine in a simplified kinetic model of cocaine abuse.

PMID- 24125118
TI  - Synonymous nucleotide polymorphisms influence Dombrock blood group protein
      expression in K562 cells.
AB  - To gain further insight into ART4 (DO) gene alleles (DO*A, DO*JO1, DO*A-WL,
      DO*DOYA, DO*B, DO*B-WL, DO*B-SH-Q149K, DO*B-(WL)-I175N, DO*HY1, DO*HY2, DO*DOMR)
      and evaluate the impact of synonymous nucleotide polymorphisms on protein
      expression and mRNA accumulation of DO*A-HA, DO*A-SH and DO*B-SH alleles, human
      erythroleukaemic K562 cells were transducted with variant DO-lentiviral particles
      and analysed by flow cytometry and quantitative reverse transcription polymerase
      chain reaction. Monoclonal antibody (MoAb) detection of DO*A-HA and DO*JO1
      transductants was lower than DO*A transductants, while detection of DO*A-SH, DO*A
      WL and DO*DOYA transductants was higher. Variant DO*B alleles, i.e. DO*B-SH, DO*B
      WL, DO*HY1, DO*HY2 and DO*DOMR, showed reduced MoAb binding. The unexpected
      modifications of protein expression of the DO*A-HA, DO*A-SH and DO*B-SH alleles
      that differ from the DO*A or DO*B alleles by a single synonymous polymorphism
      were abolished by reversion, thus implying involvement of these polymorphisms.
      Depending on the Leu208 codon used, detection level ranged from 1 to 4.14. In the
      variant alleles resulting from single synonymous polymorphism, mRNA accumulation
      correlated roughly with MoAbs detection levels, suggesting post-transcriptional
      regulation. Other than a few reports involving aberrant splicing, the experiments
      described herein provide the first evidence that synonymous nucleotide
      polymorphisms can influence Dombrock blood group expression. Such polymorphisms
      should be taken into account for molecular screening and potential impact on
      transfusion. 

PMID- 24125119
TI  - Complications with Angio-SealTM vascular closure devices compared with manual
      compression after diagnostic cardiac catheterization and percutaneous coronary
      intervention.
AB  - OBJECTIVES: This study assessed and compared vascular complications in CATHs and
      PCIs using an Angio-SealTM vascular closure device (VCD) versus manual
      compression (MC). METHODS: Secondary data analysis of a population-based
      multiyear cohort database was conducted to compare femoral access-related
      vascular outcomes in cardiac procedures using VCD and MC between May 1, 2006 and
      December 31, 2010. The primary outcome was any vascular complication. Propensity
      score adjusted analysis was conducted to reduce bias associated with covariate
      imbalance between the groups compared. RESULTS: Of the 11,897 procedures, 7,063
      (59.4%) used a VCD. Vascular complications occurred in 174/8,796 (2.0%) of CATHs
      and 82/3,004 (2.7%) of PCIs. In the CATH sample, the odds of vascular
      complication were 57% lower if a VCD was used (OR = 0.43, 95% CI 0.31-0.60). For
      the PCI sample, the risk was 49% lower if a VCD was used (OR = 0.51, 95% CI 0.31
      0.81). CONCLUSIONS: A low incidence of vascular complications was observed with
      the use of an Angio-Seal VCD relative to MC for both procedures.

PMID- 24125120
TI  - Analytical performance, agreement and user-friendliness of five C-reactive
      protein point-of-care tests.
AB  - BACKGROUND: Point-of-care (POC) C-reactive protein (CRP) testing is increasingly
      used in primary care to assist general practitioners (GPs) in the diagnostic
      workup for various complaints. The present study compares analytical performance,
      agreement and user-friendliness of five of these POC CRP tests. METHODS: The
      following five POC CRP tests were evaluated: Afinion and NycoCard Reader II (both
      Alere), Eurolyser Smart 700/340 (Eurolyser), QuikRead go and QuikRead 101 (both
      Orion Diagnostica). Results were compared with those of a standard
      immunoturbidimetric method performed on a routine analyzer (Olympus AU 2700,
      Beckman Coulter). Analytical performance and agreement with the laboratory
      standard for the five different POC tests were analyzed. Subsequently, user
      friendliness of the POC tests was assessed. RESULTS: Within-day CVs varied from
      2.6% (QuikRead go) to 19.4% (Eurolyser Smart 700/340) for low CRP values (< 20
      mg/L), and 1.1% (QuikRead go) to 17.5% (Eurolyser Smart 700/340) for high values
      (> 100 mg/L). Between-day CVs varied from 4.6% (Afinion) to 30.5% (Eurolyser
      Smart 700/340) for low values and 4.0% (QuikRead go) to 18.0% (Eurolyser Smart
      700/340) for high values. With high CRP values (> 100 mg/L) agreement with the
      laboratory standard systematically decreased for all POC tests. Regarding user
      friendliness Afinion and Eurolyser Smart 700/340 were judged easiest to operate.
      CONCLUSIONS: Analytical performance, agreement, and user-friendliness of the POC
      CRP tests varied considerably, yet overall four devices showed adequate
      analytical performance and agreement.

PMID- 24125121
TI  - Short synthesis of 3-(hydroxymethyl)xylitol and structure revision of the anti
      diabetic natural product from Casearia esculenta.
AB  - 3-(Hydroxymethyl)xylitol, a compound reportedly isolated from the root of
      Casearia esculenta (Roxb.), along with its three possible stereoisomers, has been
      synthesized for the first time by way of a triple dihydroxylation reaction
      performed upon the simplest cross-conjugated hydrocarbon, [3]dendralene. The data
      for the natural product do not match any of the isomeric 3
      (hydroxymethyl)pentitols. The structure of the natural product from the root of
      Casearia esculenta (Roxb.) has been corrected by reanalysis of the published
      data. 

PMID- 24125122
TI  - Reply to letter to the editor.

PMID- 24125123
TI  - Response to Guzman et al.: the use of fertility awareness methods (FAM) among
      young adult Latina and black women.

PMID- 24125124
TI  - Skipping the pill-free interval: data from a Dutch national sample.
AB  - INTRODUCTION: A monthly pill-free interval is unnecessary and many women prefer
      to have fewer bleeding episodes. METHODS: Eight hundred eighteen oral
      contraceptive pill (OCP) users reported frequency of skipping the pill-free
      interval in the online 2011 Sexual Health in the Netherlands Survey. Demographics
      of women who skipped pill-free intervals regularly were compared to those of
      women who rarely skipped intervals. RESULTS: 73% of the women have ever skipped
      pill-free intervals and 38% do so regularly. Women of Dutch or Western origin and
      non-religious women skip intervals more frequently, but differences are small.
      DISCUSSION: Skipping pill-free intervals is common, even when it is not actively
      promoted. IMPLICATIONS: Women who use OCPs can and do skip pill-free intervals,
      either with or without consulting a physician. If bleeding preferences were
      structurally discussed with patients, the number of women who skip intervals may
      increase even further.

PMID- 24125125
TI  - Teaching Nursing Students and Newly Registered Nurses Strategies to Deal with
      Violent Behaviors in the Professional Practice Environment.

PMID- 24125127
TI  - Stapled double head and neck drape for otological procedures.
AB  - INTRODUCTION: During otologic surgical procedures, there is often a dilemma when
      ensuring that hair is kept out of the surgical field. For a surgeon, the simplest
      and commonest technique is to liberally shave the head, but this can cause
      aesthetic concerns for the patient. Failure to keep the area hair-free can lead
      to a range of adverse surgical outcomes including wound infection and poor scar
      cosmesis. We describe a technique used in our department to effectively control
      hair during otologic surgical procedures, with no post-operative aesthetic
      concerns. METHODS: The use of re-usable or disposable surgical drapes with
      disposable skin staples can effectively exclude hair from the operative field
      throughout the procedure, without fear of the drapes slipping or losing
      adhesiveness. RESULTS: The authors have obtained good results both during and
      after surgery, using this quick and easily learnt method, with no cases of long
      term skin damage or scarring. DISCUSSION: We find this to be an effective method
      of hair and skin preparation for otologic surgical procedures, and suggest it to
      fellow otorhinolaryngologists as a helpful alternative technique.

PMID- 24125126
TI  - Bioinformatics analyses reveal age-specific neuroimmune modulation as a target
      for treatment of high ethanol drinking.
AB  - BACKGROUND: Use of in silico bioinformatics analyses has led to important leads
      in the complex nature of alcoholism at the genomic, epigenomic, and proteomic
      level, but has not previously been successfully translated to the development of
      effective pharmacotherapies. In this study, a bioinformatics approach led to the
      discovery of neuroimmune pathways as an age-specific druggable target.
      Minocycline, a neuroimmune modulator, reduced high ethanol (EtOH) drinking in
      adult, but not adolescent, mice as predicted a priori. METHODS: Age and sex
      divergent effects in alcohol consumption were quantified in FVB/NJ * C57BL/6J F1
      mice given access to 20% alcohol using a 4 h/d, 4-day drinking-in-dark (DID)
      paradigm. In silico bioinformatics pathway overrepresentation analysis for age
      specific effects of alcohol in brain was performed using gene expression data
      collected in control and DID-treated, adolescent and adult, male mice.
      Minocycline (50 mg/kg i.p., once daily) or saline alone was tested for an effect
      on EtOH intake in the F1 and C57BL/6J (B6) mice across both age and gender
      groups. Effects of minocycline on the pharmacokinetic properties of alcohol were
      evaluated by comparing the rates of EtOH elimination between the saline- and
      minocycline-treated F1 and B6 mice. RESULTS: Age and gender differences in DID
      consumption were identified. Only males showed a clear developmental increase
      difference in drinking over time. In silico analyses revealed neuroimmune-related
      pathways as significantly overrepresented in adult, but not in adolescent, male
      mice. As predicted, minocycline treatment reduced drinking in adult, but not
      adolescent, mice. The age effect was present for both genders, and in both the F1
      and B6 mice. Minocycline had no effect on the pharmacokinetic elimination of
      EtOH. CONCLUSIONS: Our results are a proof of concept that bioinformatics
      analysis of brain gene expression can lead to the generation of new hypotheses
      and a positive translational outcome for individualized pharmacotherapeutic
      treatment of high alcohol consumption.

PMID- 24125128
TI  - Antibiotic resistance of Shewanella putrefaciens isolated from shellfish
      collected from the West Sea in Korea.
AB  - In this study, we isolated and characterized Shewanella putrefaciens from
      shellfish harvested from the West Sea in Korea. For the initial isolation of S.
      putrefaciens, LB agar plates supplemented with ferrous sulfate and sodium
      thiosulfate were inoculated with shellfish homogenates, incubated for 24h, and
      then black colonies were selected. Gram-negative and catalase-positive colonies
      were subsequently confirmed by PCR assays and API 20E kit test system. The
      Shewanella-specific 16S rRNA and gyrB genes were used to design S. putrefaciens
      specific PCR primers. From 6 species of shellfish tested, 24 S. putrefaciens
      strains were isolated. These 24 isolates had the following profiles of resistance
      against 16 antibiotics: all the isolates were resistant to cephalothin and
      vancomycin and 95.8% were resistant to ampicillin. Here, we report the isolation
      of S. putrefaciens from shellfish and our results point to a new possible route
      for exposing healthy individuals to S. putrefaciens. 

PMID- 24125129
TI  - Impact evaluation of the industrial activities in the Bay of Bakar (Adriatic Sea,
      Croatia): recent benthic foraminifera and heavy metals.
AB  - The Bay of Bakar is one of the most heavily polluted bays at the Eastern
      Adriatic. Three major industrial companies potentially endanger the bay. The
      concentration of major, minor and trace elements in surface sediments from
      thirteen stations was discussed in relation to the sediment type and
      foraminiferal assemblages. The distribution of major elements in the bay is
      influenced by geological nature of surroundings. Heavy metal distribution depends
      on pollution sources and on amount of mud fraction: fine-grained sediments are
      enriched by them in comparison with coarse-grained ones. Different sediment
      quality criteria complicate the pollution assessment in the bay. Heavy metal
      concentrations generally fall into allowed depositional values for marine
      environments; only area in front of the coke plant and the City of Bakar harbor
      is heavily polluted. Stress-tolerant foraminiferal species dominate at stations
      with higher concentrations of heavy metals and coarse-grained sediments consist
      of larger number of epifaunal taxa. 

PMID- 24125130
TI  - Concentration and composition of polycyclic aromatic hydrocarbons (PAHs) in
      plastic pellets: implications for small-scale diagnostic and environmental
      monitoring.
AB  - Plastic pellets may serve as a carrier of toxic contaminants, including
      polycyclic aromatic hydrocarbons (PAHs). Considering that beach morphodynamics
      and pellet distribution varied along the shore, and that contaminant sources may
      vary on different scales, it is expected that this variability is reflected in
      the concentration and composition of contaminants. This hypothesis was tested
      through a sampling of plastic pellets at 30 sites along the shore in Santos Bay
      (Brazil). The total PAH concentrations and the priority PAHs showed high
      variability, with no clear pattern. Their composition differed among the sampling
      sites; some of the compounds represent a potential risk to organisms. The sources
      of contamination, as indicated by the isomer ratios, were also variable among
      sites. The high small-scale spatial variability found here has implications for
      estimating the plastic pellet contamination on beaches, since a sample from a
      single site is unlikely to be representative of an entire beach. 

PMID- 24125131
TI  - Bronchial thermoplasty: safe for our severe asthma patients?

PMID- 24125132
TI  - The changing face of allergy/immunology fellowship programs.

PMID- 24125134
TI  - Risk of adverse effects, misdiagnosis, and suboptimal patient care with the use
      of over-the-counter triamcinolone. Con.

PMID- 24125133
TI  - Over-the-counter intranasal corticosteroids: why the time is now. Pro.

PMID- 24125135
TI  - Environmental exposure unit: a sensitive, specific, and reproducible methodology
      for allergen challenge.

PMID- 24125136
TI  - The burden of illness in patients with hereditary angioedema.
AB  - OBJECTIVE: Hereditary angioedema (HAE) is a rare genetic disease characterized by
      long-term recurrent attacks of subcutaneous or submucosal edema in different
      parts of the body. A comprehensive review of the literature on burden of illness
      for patients with HAE is presented. DATA SOURCES: A Boolean search was performed
      using MEDLINE and EMBASE databases and the Internet. STUDY SELECTION: Articles
      discussing aspects of the burden of illness in HAE were selected. Topics focused
      on the course of the disease, nature of attacks, treatment, quality of life, and
      costs. RESULTS: Hereditary angioedema is associated with a significant and
      multifaceted disease burden. Diagnosis is often delayed for years, with patients
      receiving ineffective treatment and unnecessary medical procedures before
      diagnosis. HAE attacks are painful, unpredictable, and debilitating and often
      require emergency medical attention. Attacks can affect a patient's daily
      activities, including work or schooling. Depression and anxiety are prevalent in
      patients with HAE. Recent advances in treatment provide patients with effective
      and well-tolerated prophylactic and on-demand therapeutic options. However, end
      points specific to HAE that better measure the impact of treatment on disease
      burden are lacking. Furthermore, there is a notable paucity of literature
      directed toward physicians who are instrumental in diagnosing and treating
      patients with HAE (eg, emergency department). CONCLUSION: More publications are
      broadening the understanding of HAE. However, important gaps remain. Effective
      management of HAE requires a more comprehensive understanding of the disease
      burden so that disease management can be individualized to meet specific patient
      needs.

PMID- 24125137
TI  - Characterization and treatment of patients with chronic rhinosinusitis and nasal
      polyps.
AB  - BACKGROUND: Patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs) may
      be subdivided into aspirin-sensitive (AS) and aspirin-tolerant (AT) populations.
      These cohorts are not well characterized. OBJECTIVE: To examine phenotypic
      characteristics and determine the extent of medical/surgical interventions in
      patients with CRS+NP and to compare the AS with the AT subset in the CRS+NP
      sample. METHODS: Retrospective chart review was performed at a tertiary academic
      respiratory hospital. Data included patient demographics, asthma severity,
      peripheral eosinophilia, Lund-Mackay computed tomographic score, symptomatic
      dysosmia, and therapeutic interventions. RESULTS: Of the 182 patients included,
      81 had aspirin sensitivity (45%) and 101 had aspirin tolerance (55%). Asthma was
      present in 94% of patients with CRS+NP (100% in AS subgroup vs 89% in AT
      subgroup, P = .001). Eighty-eight percent of the CRS+NP sample had moderate to
      severe persistent asthma. In the AS and AT subgroups, asthma severity was similar
      (P > .6). The CRS+NP sample showed a mean computed tomographic score of 14.0 (44%
      with eosinophilia and 46% with dysosmia). More severe sinus disease was noted in
      the AS group (Lund-Mackay computed tomographic scores, P = .002; olfactory
      symptoms, P = .001). Serum eosinophil levels were not statistically different
      between groups (51% in AS group, 39% in AT group, P > .1). CONCLUSION: This study
      is one of the broadest reviews of patients with CRS+NP, with unique findings in
      the high prevalence of asthma in AS and AT patients, greater olfactory
      dysfunction in AS patients, and a minority of patients with CRS+NP and
      circulating eosinophils. Most AS patients do not have increased circulating
      eosinophils, as is often believed. These results shed further light on the
      association between asthma and upper respiratory tract disease in those with
      nasal polyposis.

PMID- 24125138
TI  - Exercise-induced vocal cord dysfunction and exercise-induced laryngomalacia in
      children and adolescents: the same clinical syndrome?
AB  - BACKGROUND: Exercise-induced respiratory symptoms associated with paradoxical
      laryngeal motion are relatively common and often mistaken for asthma. Exercise
      induced vocal cord dysfunction (VCD) and exercise-induced laryngomalacia (LM)
      have been described separately in the literature but have never been
      systematically compared. OBJECTIVE: To compare subjects with a confirmed
      diagnosis of exercise-induced VCD or exercise-induced LM by performing a
      retrospective chart review of subjects who had symptoms provoked by a free
      running exercise challenge and documented concurrent paradoxical laryngeal
      motion. METHODS: Demographic and clinical characteristics were analyzed in
      patients with confirmed paradoxical motion of the vocal cords (VCD) and those
      with paradoxical arytenoid motion without abnormal vocal cord movement (LM)
      during symptoms. RESULTS: Sixty subjects with exercise-induced LM and 83 subjects
      with exercise-induced VCD were identified. Subjects with confirmed exercise
      induced VCD were slightly older, had a higher body mass index, and higher grade
      point averages compared with subjects with exercise-induced LM without abnormal
      vocal cord movement. There were no differences in sex distribution, presenting
      symptoms, reported aggravating factors other than exercise, atopic status,
      confirmed bronchospasm during symptoms, mean number of asthma controller
      medications at time of evaluation, level of athletic competition, reported
      history of acid reflux, reported history of psychiatric disorders, baseline lung
      function, or lung function during symptoms. Most subjects were not "elite"
      athletes and did not have a history of anxiety or depression. CONCLUSION: There
      were remarkably few differences between subjects with exercise-induced VCD and
      those with exercise-induced LM. Prospective controlled studies are needed to
      determine whether exercise-induced VCD and exercise-induced LM are in fact
      distinct syndromes.

PMID- 24125139
TI  - Rhinitis in a community elderly population: relationships with age, atopy, and
      asthma.
AB  - BACKGROUND: Rhinitis is one of the most frequent medical conditions. However,
      there is sparse epidemiologic evidence for rhinitis in the elderly population.
      OBJECTIVE: To investigate the prevalence of rhinitis in elderly adults and its
      relations to asthma and other comorbidities. METHODS: A cross-sectional analysis
      was performed using the baseline dataset of the Korean Longitudinal Study on
      Health and Aging, a community-based elderly population cohort in Korea (>=65
      years old). Structured questionnaires were used to define rhinitis, asthma, and
      comorbidity, and allergen skin prick tests were used to define atopy. Health
      related quality of life was assessed by short-form 36 questionnaires. RESULTS: In
      total, 982 elderly adults (98.2%) were included in the present study. The
      prevalence of rhinitis was 25.6% and did not decrease until 90 years of age. The
      prevalence of atopy was 17.2% (18.8% in participants with rhinitis), and atopy
      did not show a significant association with rhinitis. In multivariate logistic
      regression analyses, relations between asthma and rhinitis were significant.
      Among comorbid conditions, none were significantly associated with rhinitis. In
      the short-form 36 questionnaire analyses, rhinitis was independently related to a
      decrease in the physical aspects of quality of life. CONCLUSION: The present
      study found a high prevalence of nonallergic rhinitis in elderly participants,
      which was significantly related to asthma and quality of life.

PMID- 24125140
TI  - Allergic rhinitis and serum 25-hydroxyvitamin D level in Korean adults.
AB  - BACKGROUND: Recently, it has been suggested that airway hyper-responsiveness,
      asthma, and atopic dermatitis are associated with a low vitamin D level.
      OBJECTIVE: To evaluate whether the occurrence of allergic rhinitis (AR) is
      related to serum vitamin D levels in the general Korean adult population.
      METHODS: Data obtained as part of the fourth annual Korean National Health and
      Nutrition Examination Survey (2009) of 8,012 adults older than 18 years were
      analyzed. The correlation between serum 25-hydroxyvitamin D (25[OH]D) level and
      presence of AR using questionnaires on symptoms, history of diagnosis of AR, and
      rhinoscopic findings were analyzed. All estimates were calculated based on
      sampling weight. RESULTS: Mean age was 44.41 years and men constituted 49.8% of
      the sample. Participants with diagnosed AR constituted 11.1%. The mean 25(OH)D
      level of the AR group was lower than that of the non-AR group (16.71 +/- 0.30 vs
      17.75 +/- 0.25 ng/mL, P < .001). A comparison of the prevalence of AR in the 3
      groups showed that AR steadily decreased in the higher 25(OH)D groups (13.0% in
      group I [<15 ng/mL], 11.5% in group II [>=15-<25 ng/mL], and 7.2% in group III
      [>=25 ng/mL], P < .001). After adjusting for body mass index, smoking status,
      age, sex, sun exposure, income quartile, exercise, and body fat percentage, lower
      serum 25(OH)D levels remained significantly associated with the presence of AR
      compared with group III (hazard ratio 1.559 in group I and 1.430 in group II).
      CONCLUSION: This study suggested a potential association between low vitamin D
      levels and AR prevalence in Korean adults.

PMID- 24125141
TI  - Office-based exhaled nitric oxide measurement in children 4 years of age and
      older.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FENO) is increasingly being used in
      the office-based management of asthma, but data in children are limited.
      OBJECTIVES: To report FENO values in 4- to 7-year-old children with suspected
      asthma and characterize their relation to clinical variables and describe the
      relation among FENO levels, age, and sex in 4- to 18-year-old children with
      suspected asthma. METHODS: Retrospective data in 4- to 18-year-old children (n =
      825) who underwent FENO testing using the NIOX MINO device were collected and
      analyzed. Chart reviews were performed for the 4- to 7-year-old children (n =
      75). RESULTS: FENO values ranged from less than or equal to 5 to 89 ppb in 75 4-
      to 7-year-old children and less than or equal to 5 to 300 ppb in 750 > 7 to 18
      year-old children. Approximately one tenth of 4- to 7-year-old children and one
      third of > 7 to 18-year-old children had FENO values indicative of
      eosinophilic/allergic inflammation (>35 ppb). In regression analysis of the 4- to
      7-year-old children, increasing age (P = .03) and asthma severity (P = .01) were
      associated with higher FENO levels. Atopic dermatitis was significantly
      associated (P = .03), whereas allergic rhinitis was marginally associated (P =
      .06), with higher FENO levels. Inhaled corticosteroid use was associated with
      lower FENO levels (P = .02). CONCLUSION: This study characterizes the largest
      cohort of 4- to 7-year-old children to undergo FENO testing in ambulatory asthma
      management. Correlations between FENO levels and clinical variables were
      consistent with established findings in older children. This preliminary real
      world study suggests that FENO assessment may be feasible and useful in the
      office-based asthma management of children as young as 4 years.

PMID- 24125142
TI  - Automated chart review for asthma cohort identification using natural language
      processing: an exploratory study.
AB  - BACKGROUND: A significant proportion of children with asthma have delayed
      diagnosis of asthma by health care providers. Manual chart review according to
      established criteria is more accurate than directly using diagnosis codes, which
      tend to under-identify asthmatics, but chart reviews are more costly and less
      timely. OBJECTIVE: To evaluate the accuracy of a computational approach to asthma
      ascertainment, characterizing its utility and feasibility toward large-scale
      deployment in electronic medical records. METHODS: A natural language processing
      (NLP) system was developed for extracting predetermined criteria for asthma from
      unstructured text in electronic medical records and then inferring asthma status
      based on these criteria. Using manual chart reviews as a gold standard, asthma
      status (yes vs no) and identification date (first date of a "yes" asthma status)
      were determined by the NLP system. RESULTS: Patients were a group of children (n
      = 112, 84% Caucasian, 49% girls) younger than 4 years (mean 2.0 years, standard
      deviation 1.03 years) who participated in previous studies. The NLP approach to
      asthma ascertainment showed sensitivity, specificity, positive predictive value,
      negative predictive value, and median delay in diagnosis of 84.6%, 96.5%, 88.0%,
      95.4%, and 0 months, respectively; this compared favorably with diagnosis codes,
      at 30.8%, 93.2%, 57.1%, 82.2%, and 2.3 months, respectively. CONCLUSION:
      Automated asthma ascertainment from electronic medical records using NLP is
      feasible and more accurate than traditional approaches such as diagnosis codes.
      Considering the difficulty of labor-intensive manual record review, NLP
      approaches for asthma ascertainment should be considered for improving clinical
      care and research, especially in large-scale efforts.

PMID- 24125143
TI  - Diagnosis and frequency of work-exacerbated asthma among bakers.
AB  - BACKGROUND: Work-exacerbated asthma (WEA) is asthma worsened by workplace
      exposures, although the asthma is not caused by sensitizers in the work
      environment. OBJECTIVES: To evaluate the frequency of WEA in bakers reporting
      work-related respiratory symptoms and the usefulness of diagnostic tests in
      differentiating WEA from occupational asthma (OA). METHODS: The study group
      included 393 bakers reporting respiratory symptoms at the workplace. In all
      patients, questionnaire, spirometry, skin prick tests (SPTs), and evaluation of
      serum total and specific IgE levels were performed. Recognition of OA was based
      on a specific inhalation challenge test. RESULTS: Occupational asthma was found
      in 44.5% of patients, whereas WEA was recognized in 16%. The latency period was
      11.2 +/- 8.2 years in patients with OA vs 13.3 +/- 9.7 years in those with WEA.
      Sixty percent of patients with OA and 50.8% of those with WEA had positive SPT
      reactions to common allergens; occupational SPT results were positive in 74.9%
      and 34.9%, respectively. Specific IgE to flours were found in 61.7% of patients
      with OA and 28.6% of those with WEA. In addition, OA frequently coexisted with
      occupational rhinitis (53.7% of patients), whereas WEA and rhinitis were found in
      31.7% of patients. CONCLUSION: Work-exacerbated asthma was diagnosed in 16% of
      bakers who reported allergic respiratory symptoms. The specific challenge test
      for occupational allergens should be performed in bakers with suspected work
      related asthma, because an assessment of sensitization (SPT to occupational
      allergens, evaluation of specific IgE) is not specific enough to differentiate OA
      from WEA.

PMID- 24125144
TI  - The CC16 A38G polymorphism is associated with asymptomatic airway hyper
      responsiveness and development of late-onset asthma.
AB  - BACKGROUND: Clara cell secretory protein (CC16) is expressed primarily in the
      respiratory tract and is a potent anti-inflammatory agent that protects the
      airway from inflammation. The associations of the A38G polymorphism in this gene
      with asymptomatic airway hyper-responsiveness (AHR), which is considered a risk
      factor for future asthma in adults, and the development of adult-onset asthma are
      unclear. OBJECTIVE: To evaluate the association of the CC16 A38G polymorphism
      with asymptomatic AHR in healthy young adults and the development of adult-onset
      asthma and the association between plasma CC16 level according to this genotype
      and asymptomatic AHR. METHODS: Nonspecific AHR was measured in 154 asymptomatic,
      young, healthy adults using a continuous methacholine inhalation method. The
      cumulative dose values of inhaled methacholine measured at the inflection point
      at which respiratory conductance started to decrease (Dmin) were used as an index
      of AHR. Case-control analysis was performed for the association between this
      polymorphism and the development of asthma in 1,086 unrelated Japanese subjects
      (504 subjects with asthma and 582 healthy subjects). RESULTS: The 38AA + AG
      genotype was associated with lower Dmin values and lower plasma CC16 levels (P =
      .012 and .020). There was a significant positive correlation between Dmin values
      and plasma CC16 levels (P = .012). In the case-control study, the 38AA + AG
      genotype was significantly associated with late-onset asthma (onset at >40 years;
      odds ratio, 1.63; P = .016). CONCLUSION: These results suggest that the CC16 A38G
      polymorphism may play a role in asymptomatic AHR and contribute to the
      development of late-onset asthma.

PMID- 24125145
TI  - Alternative ways of expressing forced expiratory volume in the first second and
      long-term mortality in elderly patients with asthma.
AB  - BACKGROUND: Clinical and epidemiologic evidence on asthma in the elderly is
      scant. There is evidence that forced expiratory volume in the first second
      (FEV1), a commonly used indicator of overall pulmonary function, might not be an
      independent predictor of 5-year mortality in elderly patients with asthma.
      OBJECTIVE: To investigate the association between FEV1 expressed using 3
      alternative methods and 5-, 10-, and 15-year mortality in a population of elderly
      patients with asthma. METHODS: Participants in the Salute Respiratoria nell'
      Anziano study were included. Asthma was diagnosed at baseline according to
      spirometric and clinical data. Vital status at 15 years was assessed using death
      registries. FEV1 was expressed as percentage of predicted, divided by height
      cubed, and as a multiple of the sex-specific first percentile. The association
      between FEV1 and mortality was evaluated using Cox proportional hazard models.
      RESULTS: Two hundred patients were studied (52% women, mean age 73.1 years,
      standard deviation 6.2 years). All FEV1 measurements were associated with
      mortality at unadjusted analysis. After correction for potential confounders, no
      association was found between FEV1 and 5-year mortality. Only FEV1 as a multiple
      of the sex-specific first percentile was independently associated with 10-year
      (hazard ratio 0.35, 95% confidence interval 0.14-0.87) and 15-year (hazard ratio
      0.38, 95% confidence interval 0.19-0.79) mortality. CONCLUSION: Although
      extensively used, FEV1 expressed as percentage of predicted does not seem to be
      the best predictor of mortality in elderly patients with asthma. Although no
      spirometric index can predict 5-year mortality in this population, FEV1 as a
      multiple of the sex-specific first percentile should be considered when longer
      term prognostic stratification is needed.

PMID- 24125146
TI  - Association of tobacco smoke exposure and atopic sensitization.
AB  - BACKGROUND: Forty million children are regularly exposed to environmental tobacco
      smoke (ETS) each year, increasing their risk for premature death and middle ear
      and acute respiratory infections. Early life exposure to ETS also is clearly
      associated with wheezing. However, there is no clear understanding of the
      influence of ETS on the development of allergic sensitization. OBJECTIVE: To
      determine the association of combined exposure to ETS and indoor allergens on IgE
      sensitization to aeroallergens in children. METHODS: This case-control study
      enrolled 116 cases and 121 controls from low-income families from Kansas City,
      Missouri. The adjusted odds ratio was calculated using a logistic model to assess
      the association between ETS and allergic sensitization using dust allergen levels
      as a covariate. RESULTS: Thirty-six percent of atopic children and 39% of
      controls were exposed to ETS (P < .05). Unadjusted analyses showed no significant
      influence of ETS on IgE sensitization to indoor allergens. Logistic regression
      analyses also showed no significant influence of ETS on sensitization when
      adjusted for levels of allergens in the home dust and family history of allergic
      rhinitis. CONCLUSION: These data suggest that ETS exposure was not associated
      with IgE sensitization to indoor allergens, even when home allergen levels were
      taken into consideration. Further understanding of how components of tobacco
      smoke influence the immune response is necessary to interpret the disparate
      findings across studies.

PMID- 24125147
TI  - Prenatal food allergen exposures and odds of childhood peanut, tree nut, or
      sesame seed sensitization.
AB  - BACKGROUND: The prevalence of peanut (PN) and tree nut (TN) allergy in children
      has tripled in the past decade. Prenatal exposures, including maternal diet and
      medications, may account for some of this increase. In the United States,
      progesterone for luteal support in assisted reproduction is commonly formulated
      in PN or sesame seed (SS) oil. OBJECTIVE: To determine whether prenatal exposure
      to PN or SS oil as progesterone in oil increases the child's odds of PN, TN, or
      SS allergy. METHODS: Parents of 1,272 children evaluated by allergists from May
      2005 through October 2009 completed questionnaires on conception, prenatal
      exposures, dietary history, and allergic history, with review of the child's
      medical record and skin prick and specific IgE test results. Odds ratios and 95%
      confidence intervals were calculated using multivariable adjusted logistic
      regression models. RESULTS: Children of mothers with a history of infertility, in
      vitro fertilization, or use of progesterone in oil did not have increased odds of
      PN, TN, and/or SS sensitization. Maternal consumption of TNs during first 2
      trimesters was associated with 60% higher odds of having a PN/TN/SS-sensitized
      child (95% confidence interval 1.01-2.51), with similarly increased odds with
      maternal SS ingestion. Odds of PN/TN/SS sensitization were doubled in children
      with asthma or environmental allergies. CONCLUSION: Neither maternal infertility
      nor exposure to PN or SS oils through progesterone support during assisted
      reproduction treatment was associated with increased odds of PN/TN/SS
      sensitization in the child. However, maternal ingestion of TNs and SS during
      pregnancy was associated with increased odds of PN/TN/SS sensitization in the
      child.

PMID- 24125148
TI  - Effect of exogenous interferons on rhinovirus replication and airway inflammatory
      responses.
AB  - BACKGROUND: Human rhinoviruses (HRVs) are the most common cause of asthma
      exacerbations. In airway epithelial cells, the primary site of HRV infection,
      decreased production of interferons (IFNs) may result in greater susceptibility
      to HRV and worsened symptoms. Thus, exogenous IFN could supplement the innate
      immune response and provide a treatment for virus-induced asthma exacerbations.
      Furthermore, the effects of exogenous IFN could be type specific in part because
      of the cellular distribution of type 1 and type 2 IFN receptors. OBJECTIVE: To
      investigate the effects of exogenous IFNs on HRV replication in bronchial
      epithelial cells. METHODS: Frozen stocks of primary human bronchial epithelial
      cells from healthy donors were cultured in monolayers; pretreated (24 hours) with
      0.1-ng/mL, 1-ng/mL, or 10-ng/mL doses of IFN-alpha, -beta, -lambda1, or -lambda2;
      and infected with HRV-1A. Viral replication was quantified using real-time
      reverse transcription-polymerase chain reaction, and cytokine and chemokine
      secretion 24 hours after infection was measured by multiplex enzyme-linked
      immunosorbent assay. RESULTS: Compared with untreated samples, IFN-alpha, IFN
      beta, IFN-lambda1, and IFN-lambda2 (0.1 ng/mL) significantly reduced HRV
      replication after high- (P < .02) and low-dose inoculation (P < .05). Similar
      effects were seen in 1-ng/mL and 10-ng/mL doses of IFN, where HRV replication was
      significantly decreased in both high- (P < .001) and low-dose inoculation (P <
      .001). Treatment with IFNs also enhanced HRV-induced IFN-gamma-induced protein 10
      secretion (P < .001). Finally, treatment with either IFN-lambda1 or IFN-lambda2
      significantly increased HRV-induced secretion of RANTES (regulated on activation,
      normal T-expressed, and presumably secreted) (P < .05) but not IL-1beta or
      vascular endothelial growth factor. CONCLUSION: These findings suggest that
      exogenous IFNs, IFN-lambda1 in particular, warrant further study as a potential
      therapy for virus-induced asthma exacerbations.

PMID- 24125149
TI  - Safety of bronchial thermoplasty in patients with severe refractory asthma.
AB  - BACKGROUND: Patients with severe refractory asthma treated with bronchial
      thermoplasty (BT), a bronchoscopic procedure that improves asthma control by
      reducing excess airway smooth muscle, were followed up for 5 years to evaluate
      long-term safety of this procedure. OBJECTIVES: To assess long-term safety of BT
      for 5 years. METHODS: Patients with asthma aged 18 to 65 years requiring high
      dose inhaled corticosteroids (ICSs) (>750 MUg/d of fluticasone propionate or
      equivalent) and long-acting beta2-agonists (LABAs) (at least 100 MUg/d of
      salmeterol or equivalent), with or without oral prednisone (<=30 mg/d),
      leukotriene modifiers, theophylline, or other asthma controller medications were
      enrolled in the Research in Severe Asthma (RISA) Trial. Patients had a
      prebronchodilator forced expiratory volume in 1 second of 50% or more of
      predicted, demonstrated methacholine airway hyperresponsiveness, had uncontrolled
      symptoms despite taking maintenance medication, abstained from smoking for 1 year
      or greater, and had a smoking history of less than 10 pack-years. RESULTS:
      Fourteen patients (of the 15 who received active treatment in the RISA Trial)
      participated in the long-term follow-up study for 5 years. The rate of
      respiratory adverse events (AEs per patient per year) was 1.4, 2.4, 1.7, and 2.4,
      respectively, in years 2 to 5 after BT. There was a decrease in hospitalizations
      and emergency department visits for respiratory symptoms in each of years 1, 2,
      3, 4, and 5 compared with the year before BT treatment. Measures of lung function
      showed no deterioration for 5 years. CONCLUSION: Our findings suggest that BT is
      safe for 5 years after BT in patients with severe refractory asthma. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00401986.

PMID- 24125150
TI  - Efficacy and safety of beclomethasone dipropionate nasal aerosol in pediatric
      patients with seasonal allergic rhinitis.
AB  - BACKGROUND: Aerosolized intranasal corticosteroid formulations are desirable for
      many patients with allergic rhinitis (AR), especially children, who wish to avoid
      the "wet feeling" and "drip down the throat" associated with aqueous
      formulations. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol
      has been shown to be safe and effective in adolescents and adults with AR.
      OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol in pediatric
      patients with moderate to severe seasonal AR. METHODS: In this double-blinded,
      placebo-controlled study, children (6-11 years of age) with seasonal AR were
      randomized to once-daily treatment with BDP nasal aerosol 80 MUg (n = 239) or 160
      MUg (n = 242) or placebo (n = 234). The primary end point was change from
      baseline in average morning and evening reflective total nasal symptom score over
      the 2-week treatment period. RESULTS: Treatment with BDP nasal aerosol showed
      significantly greater improvements in average morning and evening reflective
      total nasal symptom score vs placebo (80 MUg, -0.71; 160 MUg, -0.76; P < .001 for
      the 2 comparisons). Similarly, significantly greater improvements in average
      morning and evening instantaneous total nasal symptom score were seen with BDP
      nasal aerosol vs placebo (80 MUg, -0.63; 160 MUg, -0.73; P < .001 for the 2
      comparisons). The incidence of adverse events from BDP nasal aerosol was
      comparable to that from placebo. CONCLUSION: BDP nasal aerosol (80 or 160 MUg/d)
      provided significant and clinically meaningful nasal symptom relief and an
      established overall safety profile similar to that of placebo, suggesting that it
      is an effective and well-tolerated treatment option for pediatric patients with
      moderate to severe seasonal AR. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT012073190.

PMID- 24125151
TI  - Allergy training and immunotherapy in Latin America: results of a regional
      overview.
AB  - BACKGROUND: One main practice gap in allergology that has been detected in
      several regions of the world is the application of specific immunotherapy (SIT).
      The prescription and practice of SIT should characterize allergologic
      specialists, but there are regional discrepancies in such practice. A detailed
      knowledge of the regulatory and legislation aspects and drawbacks would help
      improve and harmonize SIT practice. OBJECTIVE: To describe in Latin America the
      level of allergy training and the characteristics of the use of SIT, including
      the medical and legal aspects. METHODS: Three sources were used: a 24-item
      questionnaire sent to 22 allergologic leaders in 11 Latin American countries, 2
      face-to-face meetings, and information from health authorities involved in the
      approval of medical substances. RESULTS: In 56% of countries, the specialty of
      allergology is a third-level care specialty and/or a subspecialty. Two countries
      have a special training program for pediatric allergists. Passing a board
      examination is mandatory in 3 countries, and recertification every 2 to 5 years
      occurs without examination. Sublingual and subcutaneous SITs are available in all
      Latin American countries. No legislation restricts SIT prescription and it can be
      performed by nonspecialists in 7 of 11 countries. In 90% of countries, allergists
      use allergen extracts from the United States (subcutaneous immunotherapy) and
      Europe (sublingual and subcutaneous immunotherapies), and 50% also manufacture
      extracts locally. Only 1 country has legal requirements for the quality of raw
      materials. CONCLUSION: The present analysis helps to identify gaps in the field
      of allergologic training and SIT in Latin America, many of them amendable.

PMID- 24125152
TI  - Delayed anaphylaxis secondary to allergy skin testing.

PMID- 24125153
TI  - Association of urinary arsenic, heavy metal, and phthalate concentrations with
      food allergy in adults: National Health and Nutrition Examination Survey, 2005
      2006.

PMID- 24125154
TI  - Are skin tests useful in fluoroquinolone hypersensitivity diagnosis?

PMID- 24125155
TI  - Lack of allergenic soy in intralipid for total parenteral nutrition.

PMID- 24125156
TI  - Short-term omalizumab treatment in an adolescent with cutaneous mastocytosis.

PMID- 24125157
TI  - Physical training improves quality of life both in asthmatic children and their
      caregivers.

PMID- 24125158
TI  - Indoor, long-term persistence of cypress pollen allergenic potency: a 10-month
      study.

PMID- 24125159
TI  - Allergen of the month-Pellitory.

PMID- 24125160
TI  - Molecular diversity and distribution of anammox community in sediments of the
      Dongjiang River, a drinking water source of Hong Kong.
AB  - AIMS: The aim of this study was to characterize anaerobic ammonium oxidation
      (anammox) community in sediments of the Dongjiang River, a drinking water source
      of Hong Kong. METHODS AND RESULTS: The diversity and distribution of the anammox
      community were investigated based on a comparative analyses of 16S rRNA and
      hydrazine oxidation (hzo) genes of anammox bacteria. Candidatus Brocadia and two
      new anammox bacterial clusters were detected based on phylogenetic analysis of
      16S rRNA genes. In contrast, the targeting of hzo genes indicated the presence of
      only Candidatus Jettenia with four different clusters. It was found that the
      sequence diversities of hzo genes were higher than those of the 16S rRNA genes.
      The abundance of anammox bacteria varied significantly among the sediment samples
      based on qPCR. Pearson correlation analysis indicated that nitrite concentration
      was the key factor influencing the abundance of anammox bacteria. The redundance
      analysis (RDA) confirmed that the combination of the contents of nitrite and
      nitrate, and the ratio of total nitrogen vs total carbon (TN/TC) had significant
      impact on the anammox bacterial community structure. CONCLUSIONS: The results
      revealed that the diverse anammox bacteria were present in sediments of the
      Dongjiang River, and the community structures were associated with varied
      environmental factors caused by urban pollutant invasion. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This is the first report about the distribution of anammox
      bacterial community in sediments of the Dongjiang River, which provides helpful
      information of anammox niche specificity and influencing factors in the river
      ecosystem.

PMID- 24125161
TI  - Use of resources and costs associated with the treatment of Dupuytren's
      contracture at an orthopedics and traumatology surgery department in Denia
      (Spain): collagenase clostridium hystolyticum versus subtotal fasciectomy.
AB  - BACKGROUND: Our purpose was to analyze and compare the use of direct health
      resources and costs generated in the treatment of Dupuytren's contracture using
      two different techniques: subtotal fasciectomy and infiltration with Collagenase
      Clostridium Histolyticum (CCH) in regular clinical practice at the Orthopedic and
      Traumatology Surgery (OTS) Department at the Hospital de Denia (Spain). METHODS:
      Observational, retrospective study based on data from the computerized clinical
      histories of two groups of patients- those treated surgically using a one or two
      digit subtotal fasciectomy technique (FSC) and those treated with CCH
      infiltration, monitored in regular clinical practice from February, 2009 to May,
      2012. Demographic (age, sex), clinical (number of digits affected and which ones)
      and use of resources (hospitalizations, medical visits, tests and drugs) data
      were collected. Resource use and associated costs, according to the hospital's
      accounting department, were compared based on the type of treatment from Spain's
      National Health Service. RESULTS: 91 patients (48 (52.8%) in the FSC group) were
      identified. The average age and number of digits affected was 65.9 (9.2) years
      and 1.33 (0.48) digits affected in the FSC group, and 65.1 (9.7) years and 1.16
      (0.4) digits in the CCH group.Overall, the costs of treating Dupuytren's disease
      with subtotal FSC amount to ?1,814 for major ambulatory surgery and ?1,961 with
      hospital stay including admission, surgical intervention (?904), examinations,
      dressings and physiotherapy. As to collagenase infiltration, costs amount to ?952
      (including minor surgery admission, vial with product, office examination and
      dressings). Finally, comparing total costs for treatments, a savings of ?388 is
      estimated in favor of CCH treatment in the best-case scenario (patient under MAS
      system with no need for physiotherapy) and ?1,008 in the worst-case scenario
      (patient admitted to hospital needing subsequent physiotherapy), implying a
      savings of 29% and 51%, respectively. CONCLUSIONS: This study demonstrates that
      treating patients with DC by injection with CCH at the OTS department of the
      Hospital de Denia generates a total savings of 29% and 51% (?388 and ?1008)
      compared with fasciectomy at the time of treatment. Long term evolution of CCH
      treatment is uncertain and the recurrence rate unknown.

PMID- 24125162
TI  - Esophageal temperature monitoring during AF ablation: multi-sensor or single
      sensor probe? Response to letter to the editor.

PMID- 24125163
TI  - Quantitative sequence-activity model analysis of oligopeptides coupling an
      improved high-dimension feature selection method with support vector regression.
AB  - Five hundred and thirty-one physicochemical property parameters of amino acids
      were directly used as descriptors to characterize the structure of oligopeptides.
      Based on support vector regression (SVR), a novel rapid selection method called
      binary matrix resetting filter (BMRF) was proposed to nonlinearly select high
      dimensional features and then multiround last-elimination (MRLE) was used for
      subtle screening. The reserved descriptors were used to construct the regression
      model with SVR, which was then applied to the quantitative sequence-activity
      model (QSAM) analysis for two oligopeptide systems. Compared with the widely used
      16 kinds of amino acid descriptors, four QSAM modeling methods and four feature
      selection methods, our work shows a significant improvement in modeling
      performance, especially in external prediction. Furthermore, the real biochemical
      significance corresponding to reserved descriptors can be given directly, and the
      interpretability of the established QSAM model is improved significantly. This
      novel method has a high potential to become an available tool for regression
      analysis of high-dimension data, such as QSAM modeling of peptides or even
      proteins.

PMID- 24125164
TI  - Large-scale periodicity of nucleosome positioning signal in pericentric regions
      of chromosomes (Drosophila melanogaster).
AB  - Nucleosome positioning signal (NPS) in heterochromatin is not uniform. We suggest
      the analysis of its heterogeneity by correlation with periodic function (analog
      of Furrier analysis). It was established the periodical repetition of the
      nucleosome clusters of large size in pericentric regions in a discontinuous
      manner. In the 3L pericentric region, it was revealed the domination of 78-85 kbp
      wavelength in the correlation coefficient profile and also strong presentation of
      50 kbp signal. In further to centromere position, the 69 kbp value strongly
      dominates as well as the 50 kbp value in the closest proximity. In addition to
      the long wavelength signals, there are plenty of short wavelengths signals
      especially in the closest vicinity to centromere. In some positions throughout
      pericentric region of 2L chromosome, there are two sizes of repeated intermingled
      correlation signals (50, and 75 kbp) with dominating value of 75 kbp in proximity
      and 50 kbp distantly to centromere, the situation for 2R is analogous. Some genes
      with long introns support these quantitative characteristics of NPSs and to some
      extent their dominating character in each region. The characteristic repeat
      periods for 3L pericentric region coincide with the distances between
      heterochromatin epigenetic mark clusters and their distribution throughout this
      region for fly embryos, larvae, and some cell lines. 

PMID- 24125165
TI  - Analysis of the cytokine profile in the duodenal mucosa of refractory coeliac
      disease patients.
AB  - RCD [refractory CD (coeliac disease)] is characterized by severe symptoms/signs
      of malabsorption and mucosal damage unresponsive to a GFD (gluten-free diet). The
      pathogenesis of RCD is not fully understood. In the present paper, we have
      characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies
      were taken from patients with RCD, patients with active CD and normal controls
      and were analysed for inflammatory cytokines by real-time PCR and ELISA. IFN
      (interferon)-gamma and IL (interleukin)-21 transcripts were increased in active
      CD patients but not in RCD patients as compared with normal controls, whereas IL
      17A RNA was up-regulated in both active CD and RCD. No significant increase in IL
      15 transcripts was observed in both active CD and RCD, whereas IL-15 protein was
      increased in active CD. IL-6 and TNF (tumour necrosis factor)-alpha were up
      regulated only in RCD. As a proof, we present the case of a woman affected by RCD
      who responded to anti-TNF-alpha treatment with improvement of malabsorptive
      symptoms/signs but no healing of mucosal lesions. The findings indicate that the
      profile of mucosal effector cytokines differs between RCD and active CD and
      suggest that TNF-alpha, IL-6 and IL-17A, but not Th1-type cytokines, could drive
      the detrimental response in this condition.

PMID- 24125166
TI  - Incidence and long-term outcomes of squamous cell bladder cancer after deceased
      donor renal transplantation.
AB  - OBJECTIVE: To review the incidence and long-term outcomes of squamous cell
      carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS:
      Between January 1976 and March 2013, five patients from one center (0.0013%)
      developed SCC of the bladder after undergoing a deceased donor kidney transplant.
      Their relevant risk factors included long-term self-intermittent
      catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior
      history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome
      variables were overall patient survival and latency period between
      transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up
      was 94 +/- 89 (range: 4-239) months. The latency period between transplantation
      and bladder SCC was 87 +/- 87 (range: 2-228) months, and all five patients were
      immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four
      patients had suspected metastases upon presentation, and one patient presented
      with organ-confined disease. This patient underwent a radical cystectomy and
      remains disease free eight months post-operatively. Despite radical treatment,
      the remaining four patients died from metastatic disease 7 +/- 4.4 (range: 2-11)
      months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor
      prognosis particularly in renal transplant patients. Early detection with
      flexible cystourethroscopy in patients with risk factors for SCC may improve long
      term outcomes in this patient cohort.

PMID- 24125167
TI  - Mechanical characterization of ultrasonically synthesized microbubble shells by
      flow cytometry and AFM.
AB  - The mechanical properties of the shell of ultrasonically synthesized lysozyme
      microbubbles, LSMBs, were evaluated by acoustic interrogation and nanoindentation
      techniques. The Young's modulus of LSMBs was found to be 1.0 +/- 0.3 MPa and 0.6
      +/- 0.1 MPa when analyzed by flow cytometry and AFM, respectively. The shell
      elasticity and Young's modulus were not affected by the size of the microbubbles
      (MBs). The hydrogel-like protein shell of LSMBs offers a softer, more elastic and
      viscous interface compared to lipid-shelled MBs. We show that the acoustic
      interrogation technique is a real-time, fast, and high-throughput method to
      characterize the mechanical characteristics of air-filled microbubbles coated by
      a variety of materials. 

PMID- 24125168
TI  - Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel
      based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity
      and outcomes.
AB  - BACKGROUND: To evaluate feasibility and preliminary outcomes associated with
      sequential whole abdomen irradiation (WAI) as consolidative treatment following
      comprehensive surgery and systemic chemotherapy for advanced endometrial cancer.
      METHODS: We conducted a retrospective analysis of patients treated at our
      institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial
      cancer patients with histological proof of one or more sites of extra-uterine
      abdomen-confined disease, treated with WAI as part of multimodal therapy.
      Endpoints were feasibility, acute toxicity, late effects, recurrence-free
      survival (RFS) and overall survival (OS). Twenty patients were identified.
      Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18
      patients. WAI was delivered using conventional technique to a median total dose
      of 27.5 Gy. RESULTS: No grade 4 toxicities occurred during chemotherapy or
      radiotherapy. No radiation dose reduction was necessary. Three patients developed
      small bowel obstruction, all in the context of recurrent intraperitoneal disease.
      Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year
      were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%),
      respectively. On univariate Cox analysis, stage IVB and serous papillary (SP)
      histology were found to be statistically significantly (at the p = 0.05 level)
      associated with worse RFS and OS. The peritoneal cavity was the most frequent
      site of initial failure. CONCLUSIONS: Consolidative WAI following chemotherapy is
      feasible and can be performed without interruption with manageable acute and late
      toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III,
      had favorable outcomes possibly meriting prospective evaluation of the addition
      of WAI following chemotherapy in selected patients. Patients with SP do poorly
      and do not routinely benefit from this approach.

PMID- 24125169
TI  - Loss of LDOC1 expression by promoter methylation in cervical cancer cells.
AB  - Cervical cancer lacks reliable prognostic factors for both progression and
      chemotherapeutic responsiveness. The expression of the LDOC1 tumor suppressor
      candidate was therefore investigated. In four of six cervical cancer cell lines
      tested, expression of LDOC1 was silenced. Downregulation of LDOC1 could also be
      shown in biopsies of cervical cancer specimens. PCR-based promoter methylation
      analysis revealed a significant association between promoter methylation and the
      loss of LDOC1 expression, which could be reverted by DNA methyltransferase
      inhibitors. This indicates that silencing of LDOC1 is a frequent event in
      cervical cancer and may be of interest as a molecular marker in cervical cancer. 

PMID- 24125170
TI  - Polymorphic AAAG repeat length in estrogen-related receptor gamma (ERRgamma) and
      risk of breast cancer in Iranian women.
AB  - Estrogen-related receptors (ERRs) alpha, beta, and gamma are orphan nuclear
      receptors that modulate the estrogen signaling pathway and play roles in the
      regulation of breast cancer cell growth. To determine the association between
      breast cancer risk and alleles of the tetranucleotide repeat (AAAG)n in the
      intron of ERRgamma gene, a case-control study of 200 breast cancer patients and
      200 controls was performed in Iranian women. Our results demonstrate that women
      with short AAAG repeat are at higher risk of breast cancer (OR 7). This result
      suggests a possible involvement of polymorphic AAAG repeat of ERRgamma gene in
      regulating its expression. 

PMID- 24125171
TI  - [Examination of the psychometric properties of the French translation of the
      Maternal Antenatal Attachment Scale (MAAS)].
AB  - BACKGROUND: Prenatal attachment (PA) is defined as the relationship that develops
      between a woman and her foetus. Three measurements exist for evaluating PA: the
      Maternal Foetal Attachment Scale (MFAS), the Maternal Antenatal Attachment Scale
      (MAAS) and the Prenatal Attachment Inventory (PAI). Of these three, only the PAI
      has been used in French. OBJECTIVES: The overall objective of the current study
      was to evaluate the psychometric properties of this second measure of PA: the
      MAAS. This scale was developed in 1993 by Condon. The MAAS is a 19-item self
      report questionnaire which allows for calculating a total attachment score and
      two subscale scores; one score estimating the quality of the affective attachment
      experience and the other that estimates the intensity of concern about the
      foetus. For each item, the future mother provided an appreciation on a 5-point
      Likert scale (1=absence of feelings for the foetus; 5=very strong feelings for
      the foetus). METHOD: The sample was composed of 117 primiparous French females
      (27.5 +/- 4.27 years) in the third trimester of pregnancy (32.84 +/- 3.77 weeks
      of amenorrhea). The study was carried out over a period of 5 months (January-May
      2012). Each woman was asked to provide demographic data, a French version of the
      MAAS, a validated French version of the PAI, and a scale evaluating depressive
      symptoms (Edinburgh PostNatal Depression Scale, EPDS). RESULTS: The MAAS
      demonstrated moderately good psychometric properties. Condon's two-factor
      structure of MAAS was not supported in our sample. Four factors were identified
      with exploratory factor analysis. Internal consistency was satisfactory for the
      global scale and for the factor 1 but not sufficiently adequate for the other
      factors. Concurrent validity was indicated by moderate correlations between the
      global MAAS scores with the total PAI score. A weak but significant inverse
      correlation was found between the MAAS and the EPDS suggesting good divergent
      validity. CONCLUSION: The authors suggest that additional research be conducted
      on the measurement before confirming the validity of the French version.

PMID- 24125172
TI  - Nicholas reactions in the synthesis of dicobalt dibenzocyclooctyne complexes.
AB  - Hexacarbonyldicobalt complexes of biaryl-substituted 4-methoxybutynones and 4
      methoxy-2-butynes undergo intramolecular Nicholas reactions to form
      dibenzocyclooctyne-Co2(CO)6 complexes in good yields. Reductive decomplexation of
      the cyclization products is possible, and the method has been applied to a formal
      synthesis of isoschizandrin. 

PMID- 24125173
TI  - Unusual presentation of an asymptomatic pseudomeningocele within the sphenoid
      sinus.
AB  - OBJECTIVE: We report the rare case of a 55-year-old woman with an asymptomatic
      left sphenoid sinus pseudomeningocele mimicking a mucocele. CASE REPORT: A 55
      year-old woman was found to have an incidental mass in the left sphenoid sinus on
      computed tomography. Magnetic resonance imaging confirmed the presence of a
      mucocele. A left endoscopic sphenoidotomy was performed to drain the mucocele.
      Despite an anatomical puncture through a stenosed sphenoid ostium, alarmingly,
      the opening leaked cerebrospinal fluid. A dehiscent lateral wall was identified
      with a dural opening communicating with the sphenoid sinus. This was immediately
      repaired with a free nasal septal mucosal graft. Six months post-operatively, the
      patient remained free from cerebrospinal fluid leakage. CONCLUSION:
      Pseudomeningoceles are extremely rare in the absence of trauma or iatrogenic
      injury. Surgeons should be alert to their presence as they can mimic a unilateral
      mucocele or nasal polyp. Endoscopic management lends itself to a single-stage
      repair.

PMID- 24125174
TI  - Prognostic benefit of surgical management in renal cell carcinoma patients with
      thrombus extending to the renal vein and inferior vena cava: 17-year experience
      at a single center.
AB  - BACKGROUND: Management of renal cell carcinoma (RCC) with tumor thrombus
      extending to the renal vein and inferior vena cava (IVC) is challenging. The aim
      of this study was to evaluate the benefit of surgical management in such
      patients. METHODS: From February 1995 to February 2013, 520 patients were treated
      for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with
      tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were
      included in this study. The records of these 85 patients were retrospectively
      reviewed to assess the relevant clinical and pathological variables and survival.
      Prognostic factors were identified by multivariate analysis. The benefit of
      surgical management was evaluated using propensity score matching to compare
      overall survival between patients who received surgical management and those who
      did not. RESULTS: RCC was confirmed by pathological examination of surgical or
      biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%)
      received surgical management (radical nephrectomy with thrombectomy). Distant
      metastasis was identified in 45 patients (53%). The proportion of patients with
      tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%,
      14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in
      patients with thrombus extending to the renal vein and 23% in patients with
      thrombus extending to the IVC. Multivariate analysis identified thrombus
      extending to the IVC, presence of distant metastasis, surgical management, serum
      albumin concentration, serum choline esterase concentration, neutrophil
      lymphocyte ratio, and Carlson comorbidity index as independent prognostic
      factors. In propensity score-matched patients, overall survival was significantly
      longer in those who received surgical management than those who did not.
      CONCLUSIONS: Surgical management may improve the prognosis of RCC patients with
      thrombus extending to the renal vein and IVC.

PMID- 24125176
TI  - Noninvasive perioperative evaluation of right ventricular function in children
      with tetralogy of Fallot.
AB  - Early and accurate noninvasive means of identifying right ventricular (RV)
      dysfunction in children with tetralogy of Fallot (TOF) are needed. RV function
      was examined using tissue Doppler imaging (TDI), strain rate (SR), and strain
      analysis (SA) in children before (N = 37) and after (6-12 months; N = 32) TOF
      repair, and in a control group of children (N = 37). Plasma concentrations of N
      terminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase 9
      (MMP-9) were measured. TDI, SR, and SA revealed that RV systolic and diastolic
      function indices were lower preoperatively in the TOF group compared with the
      control group, and did not improve after TOF repair. Plasma NT-proBNP
      concentrations were significantly higher in the TOF group pre- and
      postoperatively compared with the control group. In the preoperative TOF group,
      NT-proBNP concentration was significantly correlated with peak systolic SR and
      systolic strain in the mid segments of RV free wall. Plasma MMP-9 concentrations
      were significantly increased in the preoperative TOF group compared with the
      control group, and significantly correlated with plasma NT-proBNP and logNT
      proBNP concentrations. RV function correlated with plasma NT-proBNP
      concentrations in children with TOF. Assessment of this noninvasive measure may
      help identify RV dysfunction in patients with TOF before they become clinically
      symptomatic. 

PMID- 24125175
TI  - Photolytic labeling to probe molecular interactions in lyophilized powders.
AB  - Local side-chain interactions in lyophilized protein formulations were mapped
      using solid-state photolytic labeling-mass spectrometry (ssPL-MS). Photoactive
      amino acid analogues (PAAs) were used as probes and either added to the
      lyophilized matrix or incorporated within the amino acid sequence of a peptide.
      In the first approach, apomyoglobin was lyophilized with sucrose and varying
      concentrations of photoleucine (L-2-amino-4,4'-azipentanoic acid; pLeu). The
      lyophilized solid was irradiated at 365 nm to initiate photolabeling. The rate
      and extent of labeling were measured using electrospray ionization/high
      performance liquid chromatography/mass spectrometry (ESI-HPLC-MS), with labeling
      reaching a plateau at ~30 min, forming up to six labeled populations. Bottom-up
      MS/MS analysis was able to provide peptide-level resolution of the location of
      pLeu. ssPL-MS was also able to detect differences in side-chain environment
      between sucrose and guanidine hydrochloride formulations. In the second approach,
      peptide GCG (1-8)* containing p-benzoyl-L-phenylalanine (pBpA) in the amino acid
      sequence was lyophilized with various excipients and irradiated. Peptide-peptide
      and peptide-excipient adducts were detected using MS. Top-down MS/MS on the
      peptide dimer provided amino acid-level resolution regarding interactions and the
      cross-linking partner for pBpA in the solid state. The results show that ssPL-MS
      can provide high-resolution information about protein interactions in the
      lyophilized environment.

PMID- 24125177
TI  - Vesicular stomatitis virus glycoprotein- and Venezuelan equine encephalitis virus
      derived glycoprotein-pseudotyped lentivirus vectors differentially transduce
      corneal endothelium, trabecular meshwork, and human photoreceptors.
AB  - The ability to deliver a large transgene efficiently to photoreceptors using
      viral vectors remains problematic and yet is critical for the future therapy of
      inherited retinal diseases such as Stargardt's and Usher's 1B. Herein, we examine
      the ocular tropism of a HIV-1-based lentivirus vector pseudotyped with Venezuelan
      equine encephalitis virus-derived glycoprotein (VEEV-G) after intraocular
      delivery to the posterior and anterior chambers of C57BL/6 wild-type mice.
      Reporter gene (EGFP) expression was evaluated using in vivo fluorescence imaging
      followed by postmortem immunohistochemistry and retinal function assessed by
      electroretinography. Intracameral administration of VEEV-G and vesicular
      stomatitis virus glycoprotein (VSV-G)-pseudotyped vectors resulted in robust
      transgene expression in the corneal endothelium and trabecular meshwork. After
      subretinal administration, onset of transgene expression was observed in the
      retinal pigment epithelium (RPE) 1 day postinjection with both VEEV-G and control
      VSV-G pseudotypes, but no significant photoreceptor transduction was apparent.
      Substantial degeneration of the outer nuclear layer was observed with VEEV-G
      pseudotyped vector, which corresponded to ablation of retinal function.
      Subretinal administration of VSV-G was observed to result in significant
      suppression of electrophysiological function compared with buffer-injected and
      uninjected control eyes. Suppression of the c-wave amplitude, in addition to
      reduced RPE65 expression, indicated potential RPE dysfunction. Ex vivo tropism of
      VSV-G was assessed using organotypic culture of explanted retina harvested from
      wild-type mice and human patients undergoing retinal detachment surgery to
      examine the prevention of transduction by physical barriers and species
      differences in tropism.

PMID- 24125178
TI  - Androstanes and pregnanes from Trichilia emetica ssp. suberosa J.J. de Wilde.
AB  - Four pregnanes: 1-methoxy-pregnan-17(R)-1,4-dien-3,16-dione (1), 1-methoxy
      pregnan-17(S)-1,4-dien-3,16-dione (2), 2,3-seco-pregnan-17(S)-2,3-dioic acid-16
      oxo-dimethyl ester (4), 2alpha,3alpha,16alpha-trihydroxy-5alpha-pregnan-17(R)-20
      yl acetate (7), three androstanes: 1-methoxy-androstan-1,4-dien-3,16-dione (3),
      2,3-seco-androstan-2,3-dioic acid-16-oxo-dimethyl ester (5), 3-methoxycarbonyl
      2,3-seco-androstan-3-oic acid-16-oxo-2,19-lactone (6), together with three known
      pregnane derivatives, were isolated from the roots of Trichilia emetica ssp.
      suberosa. Their structures were determined by means of 1D and 2D NMR
      spectroscopy, mass spectrometry analysis, as well as by quantum chemical
      calculations. 

PMID- 24125179
TI  - Over-expression of JcDGAT1 from Jatropha curcas increases seed oil levels and
      alters oil quality in transgenic Arabidopsis thaliana.
AB  - The increasing consumption of fossil fuels and petroleum products is leading to
      their rapid depletion and is a matter of concern around the globe. Substitutes of
      fossil fuels are required to sustain the pace of economic development. In this
      context, oil from the non food crops (biofuel) has shown potential to substitute
      fossil fuels. Jatropha curcas is an excellent shrub spread and naturalized across
      the globe. Its oil contains a high percentage of unsaturated fatty acids (about
      78-84% of total fatty acid content) making the oil suitable for biodiesel
      production. Despite its high oil content, it has been poorly studied in terms of
      important enzymes/genes responsible for oil biosynthesis. Here, we describe the
      isolation of the full length cDNA clone of JcDGAT1, a key enzyme involved in oil
      biosynthesis, from J. curcas seeds and manipulation of oil content and
      composition in transgenic Arabidopsis plants by its expression. Transcript
      analysis of JcDGAT1 reveals a gradual increase from early seed development to its
      maturation. Homozygous transgenic Arabidopsis lines expressing JcDGAT1 both under
      CaMV35S promoter and a seed specific promoter show an enhanced level of total oil
      content (up by 30-41%) in seeds but do not show any phenotypic differences. In
      addition, our studies also show alterations in the oil composition through
      JcDGAT1 expression. While the levels of saturated FAs such as palmitate and
      stearate in the oil do not change, there is significant reproducible decrease in
      the levels of oleic acid and a concomitant increase in levels of linolenic acid
      both under the CaMV35S promoter as well as the seed specific promoter. Our
      studies thus confirm that DGAT is involved in flux control in oil biosynthesis
      and show that JcDGAT1 could be used specifically to manipulate and improve oil
      content and composition in plants. 

PMID- 24125180
TI  - Metabolism under the spotlight in senescence.

PMID- 24125181
TI  - Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in
      patients with chronic hepatitis C virus infection.
AB  - AIM: The PNPLA3 rs738409 C>G polymorphism (encoding for I148M) has recently been
      identified as a susceptibility factor for steatosis-mediated liver damage. We
      evaluated the influence of this polymorphism on hepatocarcinogenesis in patients
      with chronic hepatitis C (CHC) virus infection. METHODS: We genotyped the
      rs738409 single nucleotide polymorphism in 358 hepatitis C-associated
      hepatocellular carcinoma (HCC) patients and correlated the age at onset of HCC
      and the interval between hepatitis C virus (HCV) infection and the development of
      HCC in patients with each genotype. RESULTS: The frequencies of CC, CG and GG
      genotypes were 27.9% (100/358), 49.2% (176/358) and 22.9% (82/358), respectively,
      and were in Hardy-Weinberg equilibrium. The median age at onset of HCC for the GG
      genotype was significantly younger compared to for non-GG genotypes (67.81 vs
      69.87 years, P < 0.001), and the median interval between HCV infection and the
      development of HCC was significantly shorter in patients with the GG genotype
      (39.96 vs 40.85 years, P = 0.008). PNPLA3 GG genotype was also associated with a
      higher aspartate aminotransferase level (69.5 vs 59.0 IU/L, P = 0.02), lower
      prothrombin time (73.0% vs 78.0%, P = 0.008) and a higher prevalence of
      histological steatosis (40.0% vs. 22.2%, P = 0.01) at the time of HCC onset.
      CONCLUSION: The PNPLA3 genotype GG may be associated with accelerated
      hepatocarcinogenesis in CHC patients through increased steatosis in the liver.

PMID- 24125182
TI  - The midkine family of growth factors: diverse roles in nervous system formation
      and maintenance.
AB  - Midkines are heparin-binding growth factors involved in a wide range of
      biological processes. Originally identified as retinoic acid inducible genes,
      midkines are widely expressed during embryogenesis with particularly high levels
      in the developing nervous system. During postnatal stages, midkine expression
      generally ceases but is often up-regulated under disease conditions, most notably
      those affecting the nervous system. Midkines are known as neurotrophic factors,
      as they promote neurite outgrowth and neuron survival in cell culture.
      Surprisingly, however, mouse embryos deficient for midkine (knockout mice) are
      phenotypically normal, which suggests functional redundancy by related growth
      factors. During adult stages, on the other hand, midkine knockout mice develop
      striking deficits in neuroprotection and regeneration after drug-induced
      neurotoxicity and injury. The detailed mechanisms by which midkine controls
      neuron formation, differentiation and maintenance remain unclear. Recent studies
      in zebrafish and chick have provided important insight into the role of midkine
      and its putative receptor, anaplastic lymphoma kinase, in cell cycle control in
      the central and peripheral nervous systems. A recent structural analysis of
      zebrafish midkine furthermore revealed essential protein domains required for
      biological activity that serve as promising novel targets for future drug
      designs. This review will summarize latest findings in the field that help to
      better understand the diverse roles of midkine in nervous system formation and
      maintenance. LINKED ARTICLES: This article is part of a themed section on
      Midkine. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24125183
TI  - Molecular mechanisms of activation in CDK2.
AB  - Cyclin-dependent kinases (CDKs) are enzymes involved in crucial cellular
      processes. Their biological activity is directly linked to their high
      conformational variability, which involves large protein conformational
      rearrangements. We present here the application of an enhancing sampling
      technique to the study of conformational transitions between the open and closed
      state of CDKs. The analysis of the conformational intermediates supports the idea
      that the process is regulated by two important protein regions, which
      sequentially rearrange in order to allow the protein to reach its final
      conformation. Furthermore, the two paths involve additional (minor) protein
      rearrangements which are specific to the paths. Our results show that our
      procedure can provide reasonable transition pathways between the two protein
      forms at a very reduced computational cost. The robustness and the simplicity of
      our approach make it of general application to describe virtually any
      macromolecular conformational transitions. 

PMID- 24125184
TI  - Clinical bacteriology of recurrent otitis media with effusion.
AB  - CONCLUSIONS: Staphylococcus species were the most common bacterial isolates from
      patients with otitis media with effusion (OME). Unexpectedly, however, there was
      no difference in the identity or antibiotic resistance of bacteria isolated from
      patients with recurrent and non-recurrent OME. OBJECTIVES: Antibiotic resistance
      has increased due to indiscriminate overuse and misuse of antibiotics. Bacterial
      strains isolated from patients with recurrent OME seem to be more pathogenic and
      more resistant to antibiotics than strains isolated from patients with non
      recurrent OME. The aim of this study was to evaluate the differences in identity
      and antibiotic sensitivity profiles of bacterial strains isolated from patients
      with recurrent and non-recurrent OME. METHODS: We collected 900 middle ear fluid
      (MEF) samples from 654 pediatric patients who underwent ventilation tube
      insertion due to OME, then compared the identity and antibiotic sensitivity
      profiles of bacterial strains. Recurrent OME was defined as a requirement for
      ventilation tube reinsertion after tube extrusion. RESULTS: There was no
      difference in the identity of bacterial isolates from patients with non-recurrent
      and recurrent OME regardless of the number of ventilation tubes inserted.
      Antibiotic sensitivity tests showed that the two groups differed in sensitivity
      to penicillin and erythromycin, but not to other antibiotics.

PMID- 24125185
TI  - Retrograde approach and soft wall reconstruction in surgery for congenital
      cholesteatoma.
AB  - CONCLUSIONS: A retrograde approach and soft wall reconstruction is thought to be
      an effective surgical approach for patients with good eustachian tube function
      and good mastoid development such as in congenital cholesteatoma. OBJECTIVE: To
      analyze the usefulness of a retrograde approach and soft wall reconstructive
      surgical treatment for congenital cholesteatoma. METHODS: Data from 24 patients
      (25 ears in total) who underwent surgical intervention for congenital
      cholesteatoma at Kanazawa University Hospital between January 2001 and July 2011
      were retrospectively reviewed. We had used a retrograde approach for congenital
      cholesteatomas in which bone is removed as necessary in a retrograde manner from
      the external auditory canal side. The extent of bone removal was determined
      according to the location of the cholesteatoma. The posterior walls of the
      external auditory canals were reconstructed with soft tissue using temporal
      fascia. RESULTS: Good preoperative mastoid development was identified in 83% of
      the patients. Postoperative recurrence was seen in 1 of 25 ears. Analysis of pre-
      and postoperative hearing ability showed significant improvement in both pure
      tone audiogram air conduction and pure tone audiogram air-bone gaps.

PMID- 24125186
TI  - Outcomes of cochlear implantation in children with CHARGE syndrome.
AB  - CONCLUSION: Regardless of the extent of inner ear anomalies and intellectual
      faculties, cochlear implantation (CI) with careful treatment planning can be a
      highly effective option for hearing rehabilitation in children with sensorineural
      hearing loss and CHARGE syndrome. OBJECTIVE: CHARGE is a mnemonic term for
      coloboma, heart defects, choanal atresia, retarded growth and development,
      genital abnormalities, and ear anomalies. CHARGE syndrome is one of the leading
      causes of congenital deafness and blindness in children. We evaluated the
      language performance of six pediatric patients with CHARGE syndrome. METHODS: Six
      patients with CHARGE syndrome underwent CI at the Asan Medical Center in Seoul
      between 2002 and 2012. The mean age of these CI patients was 4.9 years (range 2
      9.8 years). All six patients had inner ear malformations; five children had an
      auricle anomaly and otitis media with effusion; three of these cases showed
      ossicle anomalies and four patients had downward displacement of the facial nerve
      (FN) toward the promontory; five patients showed delayed development; four of
      these children had cardiovascular malformations; three patients had
      cryptorchidism; two had choanal atresia; and there was one case of coloboma.
      RESULTS: In the initial operations, two patients each were implanted with a
      CI512, CI24R, or CI24RE device. One patient initially received a CI512 device in
      the right ear, followed by a CI24RE device in the left ear. Another patient (case
      1) first received a CI24R and then CI24RST device in the right ear due to poor
      performance, but this was eventually removed due to exposure of the electrode
      from adhesive otitis media and continuing poor performance. Assessment of the
      meaningful auditory integration scale (MAIS) showed that four patients reached a
      score above 95% and one patient achieved 60%. The categories of auditory
      performance (CAP) score showed that one patient reached CAP 7 at 2 years
      postoperatively and two cases showed CAP 5.5 at 1 year after implantation, while
      the remaining two patients had CAP scores of 3 at 12 months and 4.5 at 4 years,
      respectively. The speech intelligibility rating (SIR) score at 18 months post
      surgery was 4.5 in two patients, 2.5 in two patients, and 1.5 in one case. The
      remaining patient (case 1) who was explanted showed no meaningful speech
      improvement.

PMID- 24125187
TI  - The use of electrocochleography to monitor the response of Meniere's disease
      patients to intratympanic steroids.
AB  - CONCLUSIONS: Intratympanic (IT) dexamethasone provides an alternative for
      patients with Meniere's disease (MD). A reduction of the endolymphatic hydrops is
      detected by the EcohG 1 month after the treatment. OBJECTIVE: The use of
      intratympanic corticoid injections for MD has become popular due to the lack of
      reported adverse effects, but the mechanism of action is not well established.
      This study aimed to evaluate the changes in electrocochleography (EcohG)
      measurements during IT dexamethasone therapy. METHODS: This study included 53
      patients with unilateral MD refractory to medical therapy for at least 1 year.
      Each patient was treated with a fixed protocol of three consecutive weekly
      injections of a commercial 4 mg/ml dexamethasone preparation. EcohG measurements
      were performed 1 month before and 1 month after IT steroid therapy. The SP/AP
      ratio was measured before and after the IT treatment. A Kaplan-Meier analysis was
      used to evaluate the control of vertigo over a 2-year period. RESULTS: Complete
      vertigo control (class A) was achieved in 22 patients (41.5%) at the 12-month
      follow-up and 8 patients (15.1%) at the 24-month follow-up. A significant
      reduction (p < 0.01) in the SP/AP ratio after the IT steroid treatment was
      observed.

PMID- 24125188
TI  - Contributing factors to hearing of diabetic patients in an in-hospital education
      program.
AB  - CONCLUSION: In patients with poorly controlled diabetes mellitus (DM), hearing
      disturbance was associated with renal dysfunction and diabetic neuropathy,
      represented by decreases in median nerve compound action potential amplitude.
      METHODS: The evaluation was conducted using 43 subjects who were hospitalized for
      the purpose of DM education. The mean age was 58.1 years (range 21-82 years). The
      mean HbA1c was 9.5%. The mean DM duration was 11.0 years. Renal function, retina
      condition, and nerve conduction were evaluated in relation to DM complications
      (nephropathy, retinopathy, and neuropathy). Nerve conduction studies were used to
      obtain detailed information on the condition of the peripheral nerves. After
      otological inspection, pure-tone audiometry, auditory steady-state response
      (ASSR), and distortion-product otoacoustic emissions (DPOAEs) were measured.
      Stepwise multiple linear regression was used to analyze the results in the better
      ear and worse ear. RESULTS: Decreases in median nerve compound action potential
      amplitude were associated with deterioration in pure-tone audiometry and ASSR.
      Diabetic neuropathy, creatinine clearance, diabetic nephropathy, and retinopathy
      were related to hearing in ASSR and/or DPOAEs.

PMID- 24125189
TI  - Risk factors for sensorineural hearing loss in chronic otitis media.
AB  - CONCLUSIONS: Risk factors for sensorineural hearing loss (SNHL) development in
      patients with chronic otitis media (COM) are longer duration of disease, older
      age and the presence of cholesteatoma. To prevent the expected development of
      SNHL, it is imperative to treat COM actively. OBJECTIVES: To assess the severity
      of SNHL in patients with unilateral COM and to define risk factors for its
      development. METHODS: The study included 317 patients with unilateral COM. Mean
      age was 28.7 +/- 16.7 years (range 7-78 years) and mean duration of disease was
      12.2 +/- 11.3 years (range 0.25-60 years). In all patients, air conduction (AC)
      and bone conduction (BC) thresholds in both ears were measured at 500, 1000, 2000
      and 4000 Hz. The parameters evaluated were demographics, duration of disease,
      presence and location of cholesteatoma and otologic history. RESULTS: The
      difference in mean BC thresholds between the diseased ears and the healthy ears
      was statistically significant, ranging from 4.55 +/- 10.89 dB to 12.55 +/- 19.09
      dB across the measured frequency range (p < 0.0001). Multivariate regression
      analysis revealed statistically significant correlations between advanced age,
      longer duration of disease and presence of cholesteatoma, and the BC threshold
      differences between the affected and healthy ears.

PMID- 24125190
TI  - The natural course of allergic rhinitis: a 32-year follow-up study.
AB  - CONCLUSION: Early intervention may change the natural course of allergic
      rhinitis, preventing the progression to asthma. In particular, immunotherapy
      guarantees remission of local symptoms and valid protection against local and
      bronchial complications. Symptomatic treatment represents a valid alternative; it
      is always to be preferred to abstention from any treatment. OBJECTIVES: Data
      emerging from various studies on the increase of the prevalence of allergic
      rhinitis in recent decades appear to be widely dishomogeneous. Another point that
      needs clarification is the relationship between allergic rhinitis and lower
      airways pathologies such as asthma or bronchitis. METHODS: We followed the
      evolution of allergic rhinitis in a group of patients for the last 30 years to
      highlight the efficacy of different treatments in the prevention of
      complications, specifically asthma. After 32 years (1980-2012), 46/73 (63%)
      patients completed the follow-up. RESULTS: Symptomatic drugs exhibited maximum
      efficacy from the third to the eighth year, with 13 of 15 patients reporting an
      improvement of symptoms; immunotherapy achieved the best efficacy starting from
      the sixth to the tenth year (8 of 10 patients recovered). Subsequently,
      improvements decreased in the two groups, to a steady level of 11 of 15 and 6 of
      10 recovered patients. Asthma developed in 3 of 46 patients and only among
      patients that were not treated.

PMID- 24125191
TI  - Vocal and ventricular fold lateralization using crossing sutures with the
      thyroplasty window technique for bilateral vocal fold immobility: long-term
      results.
AB  - CONCLUSIONS: Vocal and ventricular fold lateralization using crossing sutures
      with the thyroplasty window technique is an effective and durable procedure for
      the management of patients with bilateral vocal fold immobility. OBJECTIVES: To
      review the long-term results of bilateral vocal fold immobility in 26 patients
      treated with vocal and ventricular fold lateralization using crossing sutures
      with the thyroplasty window technique over a 6-year period. METHODS: This
      retrospective study examined patients with a minimum follow-up of 1 year. The
      main outcome measures used were the modified Medical Research Council (MRC)
      dyspnoea scale and the assessment of voice quality pre- and postoperatively using
      the Likert method. RESULTS: The mean follow-up period was 23.77 +/- 12.01 months.
      All patients reported marked symptomatic improvement in dyspnoea (p = 0.0001).
      The voice quality worsened as expected; however, this difference did not reach a
      significant level (p = 0.642). Transient microaspiration was noted in seven of
      the patients and resolved in 1 or 2 days. The procedure was performed for the
      contralateral vocal fold in one case, due to the loss of suture tension. No
      patient showed aspiration postoperatively or during follow-up. All patients were
      regularly followed up for the beginning of movement of the lateralized or
      contralateral vocal folds in our outpatient clinic.

PMID- 24125192
TI  - Utility of 18F-FDG PET/CT in supracricoid partial laryngectomy.
AB  - CONCLUSION: (18)F-FDG PET/CT is a useful technique for the evaluation of
      paraglottic space invasion and lymph node metastasis in patients with
      supracricoid partial laryngectomy (SCPL). Primary SUVmax values (using 7.0 as a
      cut-off) and nodal SUVmax values (using 2.2 as a cut-off) are important for
      recurrence and poor prognosis. OBJECTIVES: The purpose of this study was to
      evaluate the usefulness of (18)F-FDG PET/CT for paraglottic space invasion and
      lymph node metastasis and the prognostic significance in SCPL. METHODS: The
      medical records of 42 patients who underwent (18)F-FDG PET/CT for SCPL before
      surgery were reviewed. RESULTS: The median primary SUVmax was 6.63 +/- 5.07 and
      the median nodal SUVmax was 1.25 +/- 1.86. The primary SUVmax values with
      paraglottic space invasion (8.34 +/- 5.92) and without (4.57 +/- 2.74) were
      significantly different (p = 0.015). The (18)F-FDG PET/CT had an accuracy of 87%
      for the identification of cervical metastases on a level-by-level basis. A median
      primary SUVmax value of 7.0 and nodal SUVmax of 2.2 were associated with
      recurrence (p = 0.022 and p = 0.009, respectively) and 5-year disease-specific
      survival (p = 0.021 and p = 0.041, respectively).

PMID- 24125193
TI  - Width of the normal facial canal measured by high-resolution cone-beam computed
      tomography.
AB  - CONCLUSIONS: In the facial canal, discrepancies between left and right side
      measurements at each point may be useful in the assessment and diagnosis of
      facial canal-related pathologies. OBJECTIVES: This study was performed to obtain
      accurate and high-resolution images of the normal facial canal and measure its
      widths on cross-sections of the canal at anatomically and clinically important
      sites using high-resolution cone-beam computed tomography (CBCT). METHODS: CBCT
      volume data of bilateral temporal bones were obtained from 28 healthy adult
      volunteers. The widths of the bony facial canals were measured at the meatal
      foramen, the cochleariform process, the stapes, the pyramidal eminence, and the
      point of emergence of the chorda tympani in the vertical segment. RESULTS: The
      widths of the facial canal at each point were similar bilaterally (r = 0.54-0.85,
      p < 0.01), but showed regional differences and site-specific variations. The
      narrowest of the five sites was the level of the meatal foramen (p < 0.05), as
      reported previously. The second narrowest site was the level of the stapes (p <
      0.01) followed in order by the level of the cochleariform process, the pyramidal
      eminence, and the point of emergence of the chorda tympanis (p < 0.01).

PMID- 24125194
TI  - Production of anti-ABO blood group antibodies after minor ABO-incompatible bone
      marrow transplantation in NOD/SCID/gamma(c)(null) mice.
AB  - ABO incompatibility is a barrier for solid organ transplantation, but not for
      hematopoietic stem cell transplantation. To investigate tolerance induction, we
      enrolled patients who had undergone minor ABO-incompatible (O into A group, n =
      6) and ABO-identical (O into O group, n = 4) bone marrow transplantation (BMT).
      None of the six O into A patients were positive for recipient-specific (anti
      blood group A) isohemagglutinins, whereas all four O into O patients were.
      Peripheral blood mononuclear cells (PBMCs) were engrafted into
      NOD/SCID/gamma(c)(null) (NOG) mice, followed by sensitization of blood group A
      red blood cells. Anti-blood group A antibodies (Abs) in the sera of the patients
      and the human PBMC-engrafted NOG mice were measured by enzyme-linked
      immunosorbent assays. Anti-blood group A Abs in the patients' sera were
      significantly correlated with anti-A isohemagglutinin titers (p < 0.01). In the
      human PBMC-engrafted NOG mice, anti-blood group A Abs were significantly lower in
      the O into A group than in the O into O group (p < 0.05), despite ex vivo
      restimulation of B cells. The results of this study suggest that long after
      receiving minor ABO-incompatible BMT, B cells derived from newly engrafted donor
      precursor cells were induced tolerance to recipient-specific antigens.

PMID- 24125196
TI  - An original versatile nonocclusive pressure-regulated blood roller pump for
      extracorporeal perfusion.
AB  - Currently, only a small number of centrifugal pumps are being used for
      hemodynamic and/or respiratory support, but all of them have limitations. This
      article aims to present the Rhone-Poulenc 06 nonocclusive pressure-regulated
      blood pump. This pump was developed in France in the 1970s and used for decades
      in perfusion for cardiopulmonary bypass procedures, cardiac or lung assist as
      well as venovenous bypass during liver transplant. The intrinsic properties of
      this pump allowed us to describe a new technique for extracorporeal lung support
      in the 1980s, using a single cannula tidal flow venovenous bypass. This pump
      compared favorably with conventional pumps in terms of flow and pressure,
      hemolysis, pulsatility, safety, and cost-effectiveness. We believe that this
      simple pump could be an alternative to more sophisticated and expensive devices. 

PMID- 24125195
TI  - Prevalence and imaging characteristics of detectable tonsilloliths on 482 pairs
      of consecutive CT and panoramic radiographs.
AB  - BACKGROUND: Recent studies suggest that tonsilloliths are clinically related to
      halitosis and tonsillar abscess. Based on our empirical knowledge, tonsilloliths
      are relatively commonly encountered in daily clinical practice. It has been
      reported that the detection rate of tonsilloliths was under 24% in previous
      reports, although experience suggests otherwise. The purpose of the study was to
      evaluate the prevalence and characteristics of tonsilloliths using computed
      tomography (CT). In addition, the possible causes of low detection rates on
      panoramic radiographs were evaluated based on comparisons between CT images and
      panoramic radiographs in order to elucidate the limitations of visualizing the
      area around the palatine tonsils on panoramic radiographs. METHODS: 482 pairs of
      CT images and panoramic radiographs were retrospectively assessed with respect to
      the presence and characteristics of tonsilloliths. In addition, the causes in
      cases of disagreement between the two modalities were analyzed. RESULTS: The
      detection rate of tonsilloliths was 46.1% using CT scans, unlike previous
      reports. The characteristics of tonsillolith were dot-like figures with about 300
      500 Hounsfield units within the palatine tonsil under the soft palate. The most
      common length of tonsilloliths was about 3 or 4 mm. As the subjects aged, the
      detection rate increased gradually. A significant difference in the tonsillolith
      detection rate was found between the over and under 40-year-old groups (p <
      0.0001). However, the detection rate of tonsilloliths was only 7.3% on panoramic
      radiographs. A significant correlation was observed between the detection rate of
      tonsilloliths on panoramic radiographs and CT number (Spearman r = 0.429), size,
      (Spearman r = 0.318), and number of tonsilloliths (Spearman r = 0.333).
      CONCLUSION: The present results suggest that tonsilloliths are relatively more
      common than previously suggested. However, panoramic radiographs detect only a
      small percentage of palatine tonsilloliths. The low detection rates on panoramic
      radiographs might be related to the degree of calcification, size, and number of
      tonsilloliths.

PMID- 24125198
TI  - Mechanical properties of nanoporous GaN and its application for separation and
      transfer of GaN thin films.
AB  - Nanoporous (NP) gallium nitride (GaN) as a new class of GaN material has many
      interesting properties that the conventional GaN material does not have. In this
      paper, we focus on the mechanical properties of NP GaN, and the detailed physical
      mechanism of porous GaN in the application of liftoff. A decrease in elastic
      modulus and hardness was identified in NP GaN compared to the conventional GaN
      film. The promising application of NP GaN as release layers in the mechanical
      liftoff of GaN thin films and devices was systematically studied. A phase diagram
      was generated to correlate the initial NP GaN profiles with the as-overgrown
      morphologies of the NP structures. The fracture toughness of the NP GaN release
      layer was studied in terms of the voided-space-ratio. It is shown that the
      transformed morphologies and fracture toughness of the NP GaN layer after
      overgrowth strongly depends on the initial porosity of NP GaN templates. The
      mechanical separation and transfer of a GaN film over a 2 in. wafer was
      demonstrated, which proves that this technique is useful in practical
      applications. 

PMID- 24125197
TI  - Genetic diversity and phylogenetic analysis of highly pathogenic avian influenza
      (HPAI) H5N1 viruses circulating in Bangladesh from 2007-2011.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 virus has been endemic in
      Bangladesh since its first isolation in February 2007. Phylogenetic analysis of
      the haemagglutinin (HA) gene of HPAI H5N1 viruses demonstrated that 25
      Bangladeshi isolates including two human isolates from 2007-2011 along with some
      isolates from neighbouring Asian countries (India, Bhutan, Myanmar, Nepal, China
      and Vietnam) segregate into two distinct clades (2.2 and 2.3). There was clear
      evidence of introduction of clade 2.3.2 and 2.3.4 viruses in 2011 in addition to
      clade 2.2 viruses that had been in circulation in Bangladesh since 2007. The data
      clearly demonstrated the movement of H5N1 strains between Asian countries
      included in this study due to migration of wild birds and/or illegal movement of
      poultry across borders. Interestingly, the two human isolates were closely
      related to the clade 2.2 Bangladeshi chicken isolates indicating that they have
      originated from chickens. Furthermore, comparative amino acid sequence analysis
      revealed several substitutions (including 189R>K and 282I>V) in HA protein of
      some clade 2.2 Bangladeshi viruses including the human isolates, suggesting there
      was antigenic drift in clade 2.2.3 viruses that were circulating between 2008 and
      2011. Overall, the data imply genetic diversity among circulating viruses and
      multiple introductions of H5N1 viruses with an increased risk of human infections
      in Bangladesh, and establishment of H5N1 virus in wild and domestic bird
      populations, which demands active surveillance.

PMID- 24125199
TI  - Integrability of zero-dimensional replica field theories at beta=1.
AB  - Building on insights from the theory of integrable lattices, the integrability is
      claimed for nonlinear replica sigma models derived in the context of real
      symmetric random matrices. Specifically, the fermionic and the bosonic replica
      partition functions are proven to form a single (supersymmetric) Pfaff-KP
      hierarchy whose replica limit is shown to reproduce the celebrated
      nonperturbative formula for the density-density eigenvalue correlation function
      in the infinite-dimensional Gaussian orthogonal ensemble. Implications of the
      formalism outlined are briefly discussed.

PMID- 24125200
TI  - Consensus time and conformity in the adaptive voter model.
AB  - The adaptive voter model is a paradigmatic model in the study of opinion
      formation. Here we propose an extension for this model, in which conflicts are
      resolved by obtaining another opinion, and analytically study the time required
      for consensus to emerge. Our results shed light on the rich phenomenology of both
      the original and extended adaptive voter models, including a dynamical phase
      transition in the scaling behavior of the mean time to consensus. 

PMID- 24125201
TI  - Arrow-arrow correlations for the six-vertex model.
AB  - The six-vertex model on a square lattice is "exactly solvable" because an exact
      formula for the free energy can be obtained by the Bethe ansatz. However, exact
      formulas for the correlations of local bulk observables, such as the orientation
      of the arrow at a given edge, are, in general, not available. In this Rapid
      Communication, we consider the isotropic "zero-field" six-vertex model at small
      Delta. We derive the long-distance asymptotic formula of arrow-arrow
      correlations, which display power law decays with one anomalous exponent. Our
      method is based on an interacting fermion representation of the six-vertex model
      and does not use any information obtained from the exact solution.

PMID- 24125202
TI  - Drag on intruders in granular beds: a boundary layer approach.
AB  - We performed a parametric study of the drag on vertical intruders with uniform
      cross sections of different sizes and shapes, from which we developed a
      semiempirical model. Baffling techniques were used to isolate the contributions
      of the intruder's different subsurfaces, and we observed size effects and force
      focusing on edges. We propose a boundary layer approach, whereby the drag is the
      surface integral of an effective stress over a monolayer of particles contacting
      the intruder. The stress has a simple lithostatic dependence and is a function of
      the orientation relative to the intruder's direction of motion. This approach is
      experimentally verified and is consistent with the semiempirical model.

PMID- 24125203
TI  - Non-mean-field behavior of critical wetting transition for short-range forces.
AB  - Critical wetting transition for short-range forces in three dimensions (d=3) is
      reinvestigated by means of Monte Carlo simulation. Using an anisotropic finite
      size scaling approach, as well as approaches that do not rely on finite size
      scaling, we show that the critical wetting transition shows clear deviation from
      mean-field behavior. We estimate that the effective critical exponent
      nu_{?}^{eff}=1.76 +/- 0.08 for J/kT=0.35 and nu_{?}^{eff}=1.85 +/- 0.07 for
      J/kT=0.25. These values are in accord with predictions of Parry et al. [Phys.
      Rev. Lett. 100, 136105 (2008)]. We also point out that the anisotropic finite
      size scaling approach in d=3 requires additional modification in order to reach
      full consistency of simulational results.

PMID- 24125204
TI  - Localizing epileptic seizure onsets with Granger causality.
AB  - Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for
      successful surgery, which usually depends on the information obtained from
      intracranial electroencephalography (IEEG) recordings. The visual criteria and
      univariate methods of analyzing IEEG recordings have not always produced clarity
      on the SOZs for resection and ultimate seizure freedom for patients. Here, to
      contribute to improving the localization of the SOZs and to understanding the
      mechanism of seizure propagation over the brain, we applied spectral
      interdependency methods to IEEG time series recorded from patients during
      seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs
      before the onset of any visible ictal activity and causal relationships involve
      the recording electrodes where clinically identifiable seizures later develop.
      These results suggest that high-frequency oscillatory network activities precede
      and underlie epileptic seizures, and that GC spectral measures derived from IEEG
      can assist in precise delineation of seizure onset times and SOZs. 

PMID- 24125205
TI  - Growth rate degeneracies in kinematic dynamos.
AB  - We consider the classical problem of kinematic dynamo action in simple steady
      flows. Due to the adjointness of the induction operator, we show that the growth
      rate of the dynamo will be exactly the same for two types of magnetic boundary
      conditions: the magnetic field can be normal (infinite magnetic permeability,
      also called pseudovacuum) or tangent (perfect electrical conductor) to the
      boundaries of the domain. These boundary conditions correspond to well-defined
      physical limits often used in numerical models and relevant to laboratory
      experiments. The only constraint is for the velocity field u to be reversible,
      meaning there exists a transformation changing u into -u. We illustrate this
      surprising property using S_{2}T_{2} type of flows in spherical geometry inspired
      by [Dudley and James, Proc. R. Soc. London A 425, 407 (1989)]. Using both types
      of boundary conditions, it is shown that the growth rates of the dynamos are
      identical, although the corresponding magnetic eigenmodes are drastically
      different.

PMID- 24125206
TI  - Thermal energy density of dust in dusty plasmas: experiment and theory.
AB  - A surprising observation in dusty plasma experiments is that the dust thermal
      energy density, P_{d}?n_{d}T_{d}, is typically much greater than n_{d}T_{n}
      (where n_{d} and T_{d} are the dust density and temperature, and T_{n} is the
      neutral temperature), even though the dust particles would be expected to be in
      thermal equilibrium with the neutrals. We show here, theoretically and
      experimentally, that the anomalously high dust thermal energy density can be
      accounted for if electrostatic interactions between the dust particles and the
      background plasma are taken into account. Thus, the dust pressure in dusty plasma
      is mostly of electrostatic origin.

PMID- 24125207
TI  - Multiple flat photonic bands with finite Chern numbers.
AB  - We show both analytically and numerically that there is an infinite number of
      flat bands with different Chern numbers in a two-dimensional magnetic photonic
      crystal at nearly the same frequency determined by the condition that the
      effective magnetic permeability MU_{eff}~-1. This opens the door to explore the
      physics involving higher order topological invariants in this system. The
      frequency of these states can be flexibly tuned by an external magnetic field.

PMID- 24125208
TI  - Generalized extended Navier-Stokes theory: multiscale spin relaxation in
      molecular fluids.
AB  - This paper studies the relaxation of the molecular spin angular velocity in the
      framework of generalized extended Navier-Stokes theory. Using molecular dynamics
      simulations, it is shown that for uncharged diatomic molecules the relaxation
      time decreases with increasing molecular moment of inertia per unit mass. In the
      regime of large moment of inertia the fast relaxation is wave-vector independent
      and dominated by the coupling between spin and the fluid streaming velocity,
      whereas for small inertia the relaxation is slow and spin diffusion plays a
      significant role. The fast wave-vector-independent relaxation is also observed
      for highly packed systems. The transverse and longitudinal spin modes have, to a
      good approximation, identical relaxation, indicating that the longitudinal and
      transverse spin viscosities have same value. The relaxation is also shown to be
      isomorphic invariant. Finally, the effect of the coupling in the zero frequency
      and wave-vector limit is quantified by a characteristic length scale; if the
      system dimension is comparable to this length the coupling must be included into
      the fluid dynamical description. It is found that the length scale is independent
      of moment of inertia but dependent on the state point. 

PMID- 24125209
TI  - Stochastic thermodynamics of active Brownian particles.
AB  - Examples of self-propulsion in strongly fluctuating environments are abundant in
      nature, e.g., molecular motors and pumps operating in living cells. Starting from
      the Langevin equation of motion, we develop a stochastic thermodynamic
      description of noninteracting self-propelled particles using simple models of
      velocity-dependent forces. We derive fluctuation theorems for entropy production
      and a modified fluctuation-dissipation relation, characterizing the linear
      response in nonequilibrium steady states. We study these notions in a simple
      model of molecular motors, and in the Rayleigh-Helmholtz and energy-depot models
      of self-propelled particles. 

PMID- 24125210
TI  - Quest for absolute zero in the presence of external noise.
AB  - A reciprocating quantum refrigerator is analyzed with the intention to study the
      limitations imposed by external noise. In particular we focus on the behavior of
      the refrigerator when it approaches the absolute zero. The cooling cycle is based
      on the Otto cycle with a working medium constituted by an ensemble of
      noninteracting harmonic oscillators. The compression and expansion segments are
      generated by changing an external parameter in the Hamiltonian. In this case the
      force constant of the harmonic oscillators momega^{2} is modified from an initial
      to a final value. As a result, the kinetic and potential energy of the system do
      not commute causing frictional losses. By proper choice of scheduling function
      omega(t) frictionless solutions can be obtained in the noiseless case. We examine
      the performance of a refrigerator subject to noise. By expanding from the
      adiabatic limit we find that the external noise, Gaussian phase, and amplitude
      noises reduce the amount of heat that can be extracted but nevertheless the zero
      temperature can be approached.

PMID- 24125211
TI  - Nonlinear subdiffusive fractional equations and the aggregation phenomenon.
AB  - In this article we address the problem of the nonlinear interaction of
      subdiffusive particles. We introduce the random walk model in which statistical
      characteristics of a random walker such as escape rate and jump distribution
      depend on the mean density of particles. We derive a set of nonlinear
      subdiffusive fractional master equations and consider their diffusion
      approximations. We show that these equations describe the transition from an
      intermediate subdiffusive regime to asymptotically normal advection-diffusion
      transport regime. This transition is governed by nonlinear tempering parameter
      that generalizes the standard linear tempering. We illustrate the general results
      through the use of the examples from cell and population biology. We find that a
      nonuniform anomalous exponent has a strong influence on the aggregation
      phenomenon.

PMID- 24125212
TI  - Nonequilibrium work and entropy production by quantum projective measurements.
AB  - We study the thermodynamic notion of quantum projective measurements, using a
      framework for the fluctuation theorem of nonequilibrium work. The energy change
      induced by measurements satisfies the Jarzynski equality, leading us to the
      interpretation that the quantum projective measurements perform nonequilibrium
      work on the measured system. The work average exhibits intriguing limiting
      behaviors due to the heat-up effect caused by repeated measurements and the
      quantum Zeno effect caused by measurements of an infinite frequency. If the
      measured system relaxes back to its initial equilibrium state, the work is
      completely dissipated in the form of heat into a reservoir. The corresponding
      entropy increase in the reservoir is shown to be not less than the von Neumann
      entropy change generated during the course of the measurements, proving
      Landauer's principle. 

PMID- 24125213
TI  - Statistics of avalanches with relaxation and Barkhausen noise: a solvable model.
AB  - We study a generalization of the Alessandro-Beatrice-Bertotti-Montorsi (ABBM)
      model of a particle in a Brownian force landscape, including retardation effects.
      We show that under monotonous driving the particle moves forward at all times, as
      it does in absence of retardation (Middleton's theorem). This remarkable property
      allows us to develop an analytical treatment. The model with an exponentially
      decaying memory kernel is realized in Barkhausen experiments with eddy-current
      relaxation and has previously been shown numerically to account for the
      experimentally observed asymmetry of Barkhausen pulse shapes. We elucidate
      another qualitatively new feature: the breakup of each avalanche of the standard
      ABBM model into a cluster of subavalanches, sharply delimited for slow relaxation
      under quasistatic driving. These conditions are typical for earthquake dynamics.
      With relaxation and aftershock clustering, the present model includes important
      ingredients for an effective description of earthquakes. We analyze
      quantitatively the limits of slow and fast relaxation for stationary driving with
      velocity v>0. The v-dependent power-law exponent for small velocities, and the
      critical driving velocity at which the particle velocity never vanishes, are
      modified. We also analyze nonstationary avalanches following a step in the
      driving magnetic field. Analytically, we obtain the mean avalanche shape at fixed
      size, the duration distribution of the first subavalanche, and the time
      dependence of the mean velocity. We propose to study these observables in
      experiments, allowing a direct measurement of the shape of the memory kernel and
      tracing eddy current relaxation in Barkhausen noise.

PMID- 24125214
TI  - Everlasting effect of initial conditions on single-file diffusion.
AB  - We study the dynamics of a tagged particle in an environment of point Brownian
      particles with hard-core interactions in an infinite one-dimensional channel (a
      single-file model). In particular, we examine the influence of initial conditions
      on the dynamics of the tagged particle. We compare two initial conditions: equal
      distances between particles and uniform density distribution. The effect is shown
      by the differences of mean-square-displacement and correlation function for the
      two ensembles of initial conditions. We discuss the violation of Einstein
      relation, and its dependence on the initial condition, and the difference between
      time and ensemble averaging. More specifically, using the Jepsen line, we will
      discuss how transport coefficients, like diffusivity, depend on the initial
      state. Our work shows that initial conditions determine the long time limit of
      the dynamics, and in this sense the system never forgets its initial state in
      complete contrast with thermal systems (i.e., a closed system that attains
      equilibrium independent of the initial state).

PMID- 24125215
TI  - Density-independent model of self-propelled particles.
AB  - We examine a density-independent modification of the Vicsek model in which a
      particle interacts with neighbors defined by Delaunay triangulation. To feasibly
      simulate the model, an algorithm for repairing the triangulation over time was
      developed. This algorithm may also be applied to any time varying two-dimensional
      Delaunay triangulation. This model exhibits a continuous phase transition with
      noise, and a distinct set of critical exponents were measured which satisfy a
      hyperscaling relationship. The critical exponents are found to vary between a low
      and high velocity regime, but they are robust under the inclusion of a repulsive
      interaction. We present evidence that the correlation length approximately scales
      with the size of the system even in the ordered phase.

PMID- 24125216
TI  - Spectral analysis and slow spreading dynamics on complex networks.
AB  - The susceptible-infected-susceptible (SIS) model is one of the simplest
      memoryless systems for describing information or epidemic spreading phenomena
      with competing creation and spontaneous annihilation reactions. The effect of
      quenched disorder on the dynamical behavior has recently been compared to
      quenched mean-field (QMF) approximations in scale-free networks. QMF can take
      into account topological heterogeneity and clustering effects of the activity in
      the steady state by spectral decomposition analysis of the adjacency matrix.
      Therefore, it can provide predictions on possible rare-region effects, thus on
      the occurrence of slow dynamics. I compare QMF results of SIS with simulations on
      various large dimensional graphs. In particular, I show that for Erdos-Renyi
      graphs this method predicts correctly the occurrence of rare-region effects. It
      also provides a good estimate for the epidemic threshold in case of percolating
      graphs. Griffiths Phases emerge if the graph is fragmented or if we apply a
      strong, exponentially suppressing weighting scheme on the edges. The latter model
      describes the connection time distributions in the face-to-face experiments. In
      case of a generalized Barabasi-Albert type of network with aging connections,
      strong rare-region effects and numerical evidence for Griffiths Phase dynamics
      are shown. The dynamical simulation results agree well with the predictions of
      the spectral analysis applied for the weighted adjacency matrices.

PMID- 24125217
TI  - Quantum fidelity for degenerate ground states in quantum phase transitions.
AB  - Spontaneous symmetry breaking in quantum phase transitions leads to a system
      having degenerate ground states in its broken-symmetry phase. In order to detect
      all possible degenerate ground states for a broken-symmetry phase, we introduce a
      quantum fidelity defined as an overlap measurement between a system ground state
      and an arbitrary reference state. If a system has N-fold degenerate ground states
      in a broken-symmetry phase, the quantum fidelity is shown to have N different
      values with respect to an arbitrarily chosen reference state. The quantum
      fidelity then exhibits an N-multiple bifurcation as an indicator of a quantum
      phase transition without knowing any detailed broken symmetry between a broken
      symmetry phase and a symmetry phase as a system parameter crosses its critical
      value (i.e., a multiple bifurcation point). Each order parameter, characterizing
      a broken-symmetry phase from each degenerate ground state reveals an N-multiple
      bifurcation. Furthermore, it is shown that it is possible to specify how each
      order parameter calculated from degenerate ground states transforms under a
      subgroup of a symmetry group of the Hamiltonian. Examples are given through study
      of the quantum q-state Potts models with a transverse magnetic field by employing
      tensor network algorithms based on infinite-size lattices. For any q, a general
      relation between the local order parameters is found to clearly show the subgroup
      of the Z_{q} symmetry group. In addition, we systematically discuss criticality
      in the q-state Potts model.

PMID- 24125218
TI  - Quantum spin-1 anisotropic ferromagnetic Heisenberg model in a crystal field: a
      variational approach.
AB  - A variational approach based on Bogoliubov inequality for the free energy is
      employed in order to treat the quantum spin-1 anisotropic ferromagnetic
      Heisenberg model in the presence of a crystal field. Within the Bogoliubov scheme
      an improved pair approximation has been used. The temperature-dependent
      thermodynamic functions have been obtained and provide much better results than
      the previous simple mean-field scheme. In one dimension, which is still
      nonintegrable for quantum spin-1, we get the exact results in the classical
      limit, or near-exact results in the quantum case, for the free energy,
      magnetization, and quadrupole moment, as well for the transition temperature. In
      two and three dimensions the corresponding global phase diagrams have been
      obtained as a function of the parameters of the Hamiltonian. First-order
      transition lines, second-order transition lines, tricritical and tetracritical
      points, and critical endpoints have been located through the analysis of the
      minimum of the Helmholtz free energy and a Landau-like expansion in the
      approximated free energy. Only first-order quantum transitions have been found at
      zero temperature. Limiting cases, such as isotropic Heisenberg, Blume-Capel, and
      Ising models, have been analyzed and compared to previous results obtained from
      other analytical approaches as well as from Monte Carlo simulations.

PMID- 24125219
TI  - Collisional relaxation of two-dimensional self-gravitating systems.
AB  - Systems with long range interactions present generically the formation of
      quasistationary long-lived nonequilibrium states. These states relax to Boltzmann
      equilibrium following a dynamics which is not well understood. In this paper we
      study this process in two-dimensional inhomogeneous self-gravitating systems.
      Using the Chandrasekhar-or local-approximation we write a simple approximate
      kinetic equation for the relaxation process, obtaining a Fokker-Planck equation
      for the velocity distribution with explicit analytical diffusion coefficients.
      Performing molecular dynamics simulations and comparing them with the evolution
      predicted by the Fokker-Planck equation, we observe a good agreement with the
      model for all the duration of the relaxation, from the formation of the
      quasistationary state to thermal equilibrium. We observe however an overestimate
      or underestimate of the relaxation rate of the particles with the slower or
      larger velocities, respectively. It is due to systematic errors in estimating the
      velocities of the particles at the moment of the collisions, inherent to the
      Chandrasekhar approximation when applied to inhomogeneous systems. Theory and
      simulations give a scaling of the relaxation time proportional to the number of
      particles in the system. 

PMID- 24125220
TI  - Beyond the Young-Laplace model for cluster growth during dewetting of thin films:
      effective coarsening exponents and the role of long range dewetting interactions.
AB  - Long range dewetting forces acting across thin films, such as the fundamental van
      der Waals interactions, may drive the formation of large clusters (tall
      multilayer islands) and pits, observed in thin films of diverse materials such as
      polymers, liquid crystals, and metals. In this study we further develop the
      methodology of the nonequilibrium statistical mechanics of thin films coarsening
      within continuum interface dynamics model incorporating long range dewetting
      interactions. The theoretical test bench model considered here is a
      generalization of the classical Mullins model for the dynamics of solid film
      surfaces. By analytic arguments and simulations of the model, we study the
      coarsening growth laws of clusters formed in thin films due to the dewetting
      interactions. The ultimate cluster growth scaling laws at long times are strongly
      universal: Short and long range dewetting interactions yield the same coarsening
      exponents. However, long range dewetting interactions, such as the van der Waals
      forces, introduce a distinct long lasting early time scaling behavior
      characterized by a slow growth of the cluster height/lateral size aspect ratio
      (i.e., a time-dependent Young angle) and by effective coarsening exponents that
      depend on cluster size. In this study, we develop a theory capable of
      analytically calculating these effective size-dependent coarsening exponents
      characterizing the cluster growth in the early time regime. Such a pronounced
      early time scaling behavior has been indeed seen in experiments; however, its
      physical origin has remained elusive to this date. Our theory attributes these
      observed phenomena to ubiquitous long range dewetting interactions acting across
      thin solid and liquid films. Our results are also applicable to cluster growth in
      initially very thin fluid films, formed by depositing a few monolayers or by a
      submonolayer deposition. Under this condition, the dominant coarsening mechanism
      is diffusive intercluster mass transport while the cluster coalescence plays a
      minor role, both in solid and in fluid films. 

PMID- 24125221
TI  - Distributions of time averages for weakly chaotic systems: the role of infinite
      invariant density.
AB  - Distributions of time averaged observables are investigated using deterministic
      maps with N indifferent fixed points and N-state continuous time random walk
      processes associated with them. In a weakly chaotic phase, namely when separation
      of trajectories is subexponential, maps are characterized by an infinite
      invariant density. We find that the infinite density can be used to calculate the
      distribution of time averages of integrable observables with a formula recently
      obtained by Rebenshtok and Barkai. As an example we calculate distributions of
      the average position of the particle and average occupation fractions. Our work
      provides the distributional limit theorem for time averages for a wide class of
      nonintegrable observables with respect to the infinite invariant density, in
      other words it deals with the situation where the Darling-Kac-Aaronson theorem
      does not hold.

PMID- 24125222
TI  - Disrupted coarsening in complex Cahn-Hilliard dynamics.
AB  - Predicting the pattern formation in a system maintained far from equilibrium is a
      complex task. For a given dynamics governed by the evolution of a conservative
      order parameter, recent investigations have demonstrated that the knowledge of
      the long time expression of the order parameter is sufficient to predict the
      existence of disrupted coarsening, i.e., the pinning of the inhomogeneities
      wavelength to a well defined value. However, there exists some dynamics for which
      the asymptotic form of the order parameter remains unknown. The Cahn-Hilliard
      like equation used to describe the stability of solids under irradiation belongs
      to this class of equations. In this paper, we present an alternative to predict
      the patterning induced by this equation. Based on a simple ansatz, we calculated
      the form factor and proved that a disrupted coarsening takes place in such
      dynamics. This disrupted coarsening results from the bifurcation of the implicit
      equation linking the characteristic length of the dynamics (k_{m}^{infinity})^{
      1} to a control parameter describing the irradiation. This analysis is supported
      by direct simulations. From this paper, it clearly appears that the bifurcation
      of k_{m}^{infinity} is a criterion for disrupted coarsening.

PMID- 24125223
TI  - Nonequilibrium identities and response theory for dissipative particles.
AB  - We derive some nonequilibrium identities such as the integral fluctuation theorem
      and the Jarzynski equality starting from a nonequilibrium state for dissipative
      classical systems. Thanks to the existence of the integral fluctuation theorem we
      can naturally introduce an entropy-like quantity for dissipative classical
      systems in far from equilibrium states. We also derive the generalized Green-Kubo
      formula as a nonlinear response theory for a steady dynamics around a
      nonequilibrium state. We numerically verify the validity of the derived formulas
      for sheared frictionless granular particles.

PMID- 24125224
TI  - Vortex distribution in a confining potential.
AB  - We study a model of interacting vortices in a type II superconductor. In the weak
      coupling limit, we constructed a mean-field theory which allows us to accurately
      calculate the vortex density distribution inside a confining potential. In the
      strong coupling limit, the correlations between the particles become important
      and the mean-field theory fails. Contrary to recent suggestions, this does not
      imply failure of the Boltzmann-Gibbs statistical mechanics, as we clearly
      demonstrate by comparing the results of molecular dynamics and Monte Carlo
      simulations. 

PMID- 24125225
TI  - Ergodic crossover in partially self-avoiding stochastic walks.
AB  - Consider a one-dimensional environment with N randomly distributed sites. An
      agent explores this random medium moving deterministically with a spatial memory
      MU. A crossover from local to global exploration occurs in one dimension at a
      well-defined memory value MU_{1}=log_{2}N. In its stochastic version, the
      dynamics is ruled by the memory and by temperature T, which affects the hopping
      displacement. This dynamics also shows a crossover in one dimension, obtained
      computationally, between exploration schemes, characterized yet by the trajectory
      size (N_{p}) (aging effect). In this paper we provide an analytical approach
      considering the modified stochastic version where the parameter T plays the role
      of a maximum hopping distance. This modification allows us to obtain a general
      analytical expression for the crossover, as a function of the parameters MU, T,
      and N_{p}. Differently from what has been proposed by previous studies, we find
      that the crossover occurs in any dimension d. These results have been validated
      by numerical experiments and may be of great value for fixing optimal parameters
      in search algorithms.

PMID- 24125226
TI  - Rerouting excitation transfers in the Fenna-Matthews-Olson complex.
AB  - We investigate, using the hierarchy method, the entanglement and the excitation
      transfer efficiency of the Fenna-Matthews-Olson (FMO) complex under two different
      local modifications: the suppression of transitions between particular sites and
      localized changes to the protein environment. We find that inhibiting the
      connection between site 5 and site 6, or completely disconnecting site 5 from the
      complex, leads to a dramatic enhancement of the entanglement between site 6 and
      site 7. Similarly, the transfer efficiency actually increases if site 5 is
      entirely disconnected from the complex. We further show that if sites 5 and 7 are
      conjointly removed, the efficiency falls. This suggests that while not
      contributing to the transport efficiency in a normal complex, site 5 may
      introduce a redundant transport route in case of damage to site 7. Our results
      suggest an overall robustness of the excitation-energy transfer in the FMO
      complex under mutations, local defects, and other abnormal situations. 

PMID- 24125227
TI  - Influence of long-range interactions on charge ordering phenomena on a square
      lattice.
AB  - Usually complex charge ordering phenomena arise due to competing interactions. We
      have studied how such ordered patterns emerge from the frustration of a long
      ranged interaction on a lattice. Using the lattice gas model on a square lattice
      with fixed particle density, we have identified several interesting phases, such
      as a generalization of Wigner crystals at low particle densities and stripe
      phases at densities between rho=1/3 and 1/2. These stripes act as domain walls in
      the checkerboard phase present at half-filling. The phases are characterized at
      zero temperatures using numerical simulations, and mean field theory is used to
      construct a finite temperature phase diagram.

PMID- 24125228
TI  - Control of logic gates by dichotomous noise in energetic and entropic systems.
AB  - We consider the stochastic response of a nonlinear dynamical system towards a
      combination of input signals. The response can assume binary values if the state
      of the system is considered to be the output and the system can make transitions
      between two states separated by an energetic or entropic barrier. We show how the
      input-output correspondence can be controlled by an external exponentially
      correlated dichotomous noise optimizing the logical response which exhibits a
      maximum at an intermediate value of correlation time. This resonance manifests
      itself as a "logical" resonance correlation effect and sets the condition for
      performance of the stochastic system as a logic gate. The role of asymmetry of
      the dichotomous noise is examined and the results on numerical simulations are
      correlated with a two-state model using a master equation approach. 

PMID- 24125229
TI  - Thermodynamic curvature for attractive and repulsive intermolecular forces.
AB  - The thermodynamic curvature scalar R for the Lennard-Jones system is evaluated in
      phase space, including vapor, liquid, and solid state. We paid special attention
      to the investigation of R along vapor-liquid, liquid-solid, and vapor-solid
      equilibria. Because R is a measure of interaction strength, we traced out the
      line R=0 dividing the phase space into regions with effectively attractive (R<0)
      or repulsive (R>0) interactions. Furthermore, we analyzed the dependence of R on
      the strength of attraction applying a perturbation ansatz proposed by Weeks
      Chandler-Anderson. Our results show clearly a transition from R>0 (for poorly
      repulsive interaction) to R<0 when loading attraction in the intermolecular
      potential. 

PMID- 24125230
TI  - Crossover behavior in driven cascades.
AB  - We propose a model which explains how power-law crossover behavior can arise in a
      system which is capable of experiencing cascading failure. In our model the
      susceptibility of the system to cascades is described by a single number, the
      propagation power, which measures the ease with which cascades propagate.
      Physically, such a number could represent the density of unstable material in a
      system, its internal connectivity, or the mean susceptibility of its component
      parts to failure. We assume that the propagation power follows an upward drifting
      Brownian motion between cascades, and drops discontinuously each time a cascade
      occurs. Cascades are described by a continuous state branching process with
      distributional properties determined by the value of the propagation power when
      they occur. In common with many cascading models, pure power-law behavior is
      exhibited at a critical level of propagation power, and the mean cascade size
      diverges. This divergence constrains large systems to the subcritical region. We
      show that as a result, crossover behavior appears in the cascade distribution
      when an average is performed over the distribution of propagation power. We are
      able to analytically determine the exponents before and after the crossover. 

PMID- 24125231
TI  - Nonequilibrium heterogeneous catalysis in the long mean-free-path regime.
AB  - It is shown that a standard principle of traditional catalysis-that a catalyst
      does not alter the final thermodynamic equilibrium of a reaction-can fail in low
      pressure, heterogeneous gas-surface reactions. Kinetic theory for this
      epicatalysis is presented, and two well-documented experimental examples are
      detailed: surface ionized plasmas and hydrogen dissociation on refractory metals.
      This phenomenon should be observable over a wide range of temperatures and
      pressures, and for a broad spectrum of heterogeneous reactions. By transcending
      some constraints of equilibrium thermodynamics, epicatalysis might provide
      additional control parameters and synthetic routes for reactions, and enable
      product streams boosted in thermochemical energy or desirable species. 

PMID- 24125232
TI  - Extended finite-size scaling of synchronized coupled oscillators.
AB  - We present a systematic analysis of dynamic scaling in the time evolution of the
      phase order parameter for coupled oscillators with nonidentical natural
      frequencies in terms of the Kuramoto model. This provides a comprehensive view of
      phase synchronization. In particular, we extend finite-size scaling (FSS) in the
      steady state to dynamics, determine critical exponents, and find the critical
      coupling strength. The dynamic scaling approach enables us to measure not only
      the FSS exponent associated with the correlation volume in finite systems but
      also thermodynamic critical exponents. Based on the extended FSS theory, we also
      discuss how the sampling of natural frequencies and thermal noise affect dynamic
      scaling, which is numerically confirmed. 

PMID- 24125233
TI  - Fence-sitters protect cooperation in complex networks.
AB  - Evolutionary game theory is one of the key paradigms behind many scientific
      disciplines from science to engineering. In complex networks, because of the
      difficulty of formulating the replicator dynamics, most of the previous studies
      are confined to a numerical level. In this paper, we introduce a vectorial
      formulation to derive three classes of individuals' payoff analytically. The
      three classes are pure cooperators, pure defectors, and fence-sitters. Here,
      fence-sitters are the individuals who change their strategies at least once in
      the strategy evolutionary process. As a general approach, our vectorial
      formalization can be applied to all the two-strategy games. To clarify the
      function of the fence-sitters, we define a parameter, payoff memory, as the
      number of rounds that the individuals' payoffs are aggregated. We observe that
      the payoff memory can control the fence-sitters' effects and the level of
      cooperation efficiently. Our results indicate that the fence-sitters' role is
      nontrivial in the complex topologies, which protects cooperation in an indirect
      way. Our results may provide a better understanding of the composition of
      cooperators in a circumstance where the temptation to defect is larger. 

PMID- 24125234
TI  - Theta-point polymers in the plane and Schramm-Loewner evolution.
AB  - We study the connection between polymers at the theta temperature on the lattice
      and Schramm-Loewner chains with constant step length in the continuum. The second
      of these realize a useful algorithm for the exact sampling of tricritical
      polymers, where finite-chain effects are excluded. The driving function computed
      from the lattice model via a radial implementation of the zipper method is shown
      to converge to Brownian motion of diffusivity kappa=6 for large times. The
      distribution function of an internal portion of walk is well approximated by that
      obtained from Schramm-Loewner chains. The exponent of the correlation length nu
      and the leading correction-to-scaling exponent Delta_{1} measured in the
      continuum are compatible with nu=4/7 (predicted for the theta point) and
      Delta_{1}=72/91 (predicted for percolation). Finally, we compute the shape factor
      and the asphericity of the chains, finding surprising accord with the theta-point
      end-to-end values.

PMID- 24125235
TI  - Minimal spanning trees at the percolation threshold: a numerical calculation.
AB  - The fractal dimension of minimal spanning trees on percolation clusters is
      estimated for dimensions d up to d=5. A robust analysis technique is developed
      for correlated data, as seen in such trees. This should be a robust method
      suitable for analyzing a wide array of randomly generated fractal structures. The
      trees analyzed using these techniques are built using a combination of Prim's and
      Kruskal's algorithms for finding minimal spanning trees. This combination reduces
      memory usage and allows for simulation of larger systems than would otherwise be
      possible. The path length fractal dimension d_{s} of MSTs on critical percolation
      clusters is found to be compatible with the predictions of the perturbation
      expansion developed by T. S. Jackson and N. Read [Phys. Rev. E 81, 021131
      (2010)].

PMID- 24125236
TI  - Frieden wave-function representations via an Einstein-Podolsky-Rosen-Bohm
      experiment.
AB  - The appearance of the spin-1/2 and spin-1 representations in the Frieden-Soffer
      extreme physical information (EPI) statistical approach to the Einstein-Podolsky
      Rosen-Bohm (EPR-Bohm) experiment is shown. In order to obtain the EPR-Bohm
      result, in addition to the observed structural and variational information
      principles of the EPI method, the condition of the regularity of the probability
      distribution is used. The observed structural information principle is obtained
      from the analyticity of the logarithm of the likelihood function. It is suggested
      that, due to the self-consistent analysis of both information principles, quantum
      mechanics is covered by the statistical information theory. The estimation of the
      angle between the analyzers in the EPR-Bohm experiment is discussed.

PMID- 24125237
TI  - Frozen into stripes: fate of the critical Ising model after a quench.
AB  - In this article we study numerically the final state of the two-dimensional
      ferromagnetic critical Ising model after a quench to zero temperature. Beginning
      from equilibrium at T_{c}, the system can be blocked in a variety of infinitely
      long lived stripe states in addition to the ground state. Similar results have
      already been obtained for an infinite temperature initial condition and an
      interesting connection to exact percolation crossing probabilities has emerged.
      Here we complete this picture by providing an example of stripe states precisely
      related to initial crossing probabilities for various boundary conditions. We
      thus show that this is not specific to percolation but rather that it depends on
      the properties of spanning clusters in the initial state.

PMID- 24125238
TI  - Self-sustained clusters and ergodicity breaking in spin models.
AB  - Self-sustained spin clusters are analytically linked to ergodicity breaking in
      fully connected Ising and Sherrington-Kirkpatick (SK) models, relating the less
      understood spin space to the well understood state space. This correspondence is
      established through the absence of clusters in the paramagnetic phase, the
      presence of one dominant cluster in the Ising ferromagnet, and the formation of
      nontrivial clusters in SK spin glass. Yet unobserved phenomena are also revealed
      such as a first order phase transition in cluster sizes in the SK ferromagnet.
      The method could be adapted to investigate other spin models.

PMID- 24125239
TI  - Excited-state quantum phase transitions in Dicke superradiance models.
AB  - We derive analytical results for various quantities related to the excited-state
      quantum phase transitions in a class of Dicke superradiance models in the
      semiclassical limit. Based on a calculation of a partition sum restricted to
      Dicke states, we discuss the singular behavior of the derivative of the density
      of states and find observables such as the mean (atomic) inversion and the boson
      (photon) number and its fluctuations at arbitrary energies. Criticality depends
      on energy and a parameter that quantifies the relative weight of rotating versus
      counterrotating terms, and we find a close analogy to the logarithmic and jump
      type nonanalyticities known from the Lipkin-Meshkov-Glick model.

PMID- 24125240
TI  - Electrical percolation in quasi-two-dimensional metal nanowire networks for
      transparent conductors.
AB  - We simulate the conductivity of quasi-two-dimensional mono- and polydisperse rod
      networks having rods of various aspect ratios (L/D = 25-800) and rod densities up
      to 100 times the critical density and assuming contact-resistance dominated
      transport. We report the rod-size dependence of the percolation threshold and the
      density dependence of the conductivity exponent over the entire L/D range
      studied. Our findings clarify the range of applicability for the popular
      widthless-stick description for physical networks of rodlike objects with modest
      aspect ratios and confirm predictions for the high-density dependence of the
      conductivity exponent obtained from modest-density systems. We also propose a
      heuristic extension to the finite-width excluded area percolation model to
      account for arbitrary distributions in rod length and validate this solution with
      numerical results from our simulations. These results are relevant to nanowire
      films that are among the most promising candidates for high performance flexible
      transparent electrodes.

PMID- 24125241
TI  - Replica-symmetry-breaking transitions and off-equilibrium dynamics.
AB  - I consider branches of replica-symmetry-breaking (RSB) solutions in glassy
      systems that display a dynamical transition at a temperature T_{d} characterized
      by a mode-coupling-theory dynamical behavior. Below T_{d} these branches of
      solutions are considered to be relevant to the system complexity and to off
      equilibrium dynamics. Under general assumptions I argue that near T_{d} it is not
      possible to stabilize the one-step (1RSB) solution beyond the marginal point by
      making a full RSB (FRSB) ansatz. However, depending on the model, there may exist
      a temperature T strictly lower than T_{d} below which the 1RSB branch can be
      continued to a FRSB branch. Such a temperature certainly exists for models that
      display the so-called Gardner transition and in this case T_{G}<T_<T_{d}. An
      analytical study in the context of the truncated model reveals that the FRSB
      branch of solutions below T is characterized by a two-plateau structure and it
      ends where the first plateau disappears. These general features are confirmed in
      the context of the Ising p-spin model with p=3 by means of a numerical solution
      of the FRSB equations. The results are discussed in connection with off
      equilibrium dynamics within Cugliandolo-Kurchan theory. In this context I assume
      that the RSB solution relevant for off-equilibrium dynamics is the 1RSB marginal
      solution in the whole range (T ,T_{d}) and it is the end point of the FRSB branch
      for T<T. Remarkably, under these assumptions it can be argued that T marks a
      qualitative change in off-equilibrium dynamics in the sense that the decay of
      various dynamical quantities changes from power law to logarithmic.

PMID- 24125242
TI  - Transport and collision dynamics in periodic asymmetric obstacle arrays: rational
      design of microfluidic rare-cell immunocapture devices.
AB  - Microfluidic obstacle arrays have been used in numerous applications, and their
      ability to sort particles or capture rare cells from complex samples has broad
      and impactful applications in biology and medicine. We have investigated the
      transport and collision dynamics of particles in periodic obstacle arrays to
      guide the design of convective, rather than diffusive, transport-based
      immunocapture microdevices. Ballistic and full computational fluid dynamics
      simulations are used to understand the collision modes that evolve in cylindrical
      obstacle arrays with various geometries. We identify previously unrecognized
      collision mode structures and differential size-based collision frequencies that
      emerge from these arrays. Previous descriptions of transverse displacements that
      assume unidirectional flow in these obstacle arrays cannot capture mode
      transitions properly as these descriptions fail to capture the dependence of the
      mode transitions on column spacing and the attendant change in the flow field.
      Using these analytical and computational simulations, we elucidate design
      parameters that induce high collision rates for all particles larger than a
      threshold size or selectively increase collision frequencies for a narrow range
      of particle sizes within a polydisperse population. Furthermore, we investigate
      how the particle Peclet number affects collision dynamics and mode transitions
      and demonstrate that experimental observations from various obstacle array
      geometries are well described by our computational model.

PMID- 24125243
TI  - Modulated two-level system: exact work statistics.
AB  - We consider an open two-level system driven by a piecewise constant periodic
      field and described by a rate equation with Fermi, Bose, and Arrhenius rates,
      respectively. We derive an analytical expression for the generating function and
      large deviation function of the work performed by the field and show that a work
      fluctuation theorem holds. 

PMID- 24125244
TI  - Relativistic Langevin dynamics in expanding media.
AB  - We study the consequences of different realizations of diffusion processes in
      relativistic Langevin simulations. We elaborate on the Ito-Stratonovich dilemma
      by showing how microscopically calculated transport coefficients as obtained from
      a Boltzmann-Fokker-Planck equation can be implemented to lead to an unambiguous
      realization of the Langevin process. Pertinent examples within the prepoint (Ito)
      and postpoint (Hanggi-Klimontovich) Langevin prescriptions are worked out
      explicitly. Deviations from this implementation are shown to generate variants of
      the Boltzmann distribution as the stationary (equilibrium) solutions. Finally, we
      explicitly verify how the Lorentz invariance of the Langevin process is
      maintained in the presence of an expanding medium, including the case of an
      "elliptic flow" transmitted to a Brownian test particle. This is particularly
      relevant for using heavy-flavor diffusion as a quantitative tool to diagnose
      transport properties of QCD matter as created in ultrarelativistic heavy-ion
      collisions.

PMID- 24125245
TI  - Increasing thermal rectification: effects of long-range interactions.
AB  - In this paper, we study the effects of the interparticle interaction range on
      heat flow. We show that, by increasing the interaction range, we may amplify the
      thermal conductivity and even change the regime of heat transport. More
      importantly, considering a crucial problem of phononics, namely, the search of a
      suitable thermal diode, we investigate the range effects in some graded systems
      in which thermal rectification is a ubiquitous phenomenon. In such graded models,
      we show that long-range interactions may significatively increase the
      rectification power and may avoid its decay with the system size, thus solving
      relevant problems of the usual proposals of rectifiers. Our results indicate that
      graded materials are genuine candidates for the actual fabrication of thermal
      diodes. 

PMID- 24125246
TI  - Optimal and suboptimal quadratic forms for noncentered Gaussian processes.
AB  - Individual random trajectories of stochastic processes are often analyzed by
      using quadratic forms such as time averaged (TA) mean square displacement (MSD)
      or velocity auto-correlation function (VACF). The appropriate quadratic form is
      expected to have a narrow probability distribution in order to reduce statistical
      uncertainty of a single measurement. We consider the problem of finding the
      optimal quadratic form that minimizes a chosen cumulant moment (e.g., the
      variance) of the probability distribution, under the constraint of fixed mean
      value. For discrete noncentered Gaussian processes, we construct the optimal
      quadratic form by using the spectral representation of cumulant moments.
      Moreover, we obtain a simple explicit formula for the smallest achievable
      cumulant moment that may serve as a quality benchmark for other quadratic forms.
      We illustrate the optimality issues by comparing the optimal variance with the
      variances of the TA MSD and TA VACF of fractional Brownian motion superimposed
      with a constant drift and independent Gaussian noise.

PMID- 24125247
TI  - Growth dominates choice in network percolation.
AB  - The onset of large-scale connectivity in a network (i.e., percolation) often has
      a major impact on the function of the system. Traditionally, graph percolation is
      analyzed by adding edges to a fixed set of initially isolated nodes. Several
      years ago, it was shown that adding nodes as well as edges to the graph can yield
      an infinite order transition, which is much smoother than the traditional second
      order transition. More recently, it was shown that adding edges via a competitive
      process to a fixed set of initially isolated nodes can lead to a delayed,
      extremely abrupt percolation transition with a significant jump in large but
      finite systems. Here we analyze a process that combines both node arrival and
      edge competition. If started from a small collection of seed nodes, we show that
      the impact of node arrival dominates: although we can significantly delay
      percolation, the transition is of infinite order. Thus, node arrival can mitigate
      the trade-off between delay and abruptness that is characteristic of explosive
      percolation transitions. This realization may inspire new design rules where
      network growth can temper the effects of delay, creating opportunities for
      network intervention and control. 

PMID- 24125248
TI  - Scaling functions for systems with finite range of interaction.
AB  - We present a numerical determination of the scaling functions of the
      magnetization, the susceptibility, and the Binder's cumulant for two
      nonequilibrium model systems with varying range of interactions. We consider
      Monte Carlo simulations of the block voter model (BVM) on square lattices and of
      the majority-vote model (MVM) on random graphs. In both cases, the satisfactory
      data collapse obtained for several system sizes and interaction ranges supports
      the hypothesis that these functions are universal. Our analysis yields an
      accurate estimation of the long-range exponents, which govern the decay of the
      critical amplitudes with the range of interaction, and is consistent with the
      assumption that the static exponents are Ising-like for the BVM and classical for
      the MVM.

PMID- 24125249
TI  - Relative stability of dynamical states and stochastic resonance in a sinusoidal
      potential.
AB  - Recently, stochastic resonance was shown to occur in underdamped periodic
      potentials at frequencies (of the drive field) close to the natural frequency at
      the minima of the potentials. In these systems the particle trajectories are not
      arbitrary at low temperatures but follow the drive field with two definite mean
      phase differences depending on the initial conditions. The trajectories are thus
      found to be in only two stable dynamical states. The occurrence of stochastic
      resonance in the periodic potentials was explained as a consequence of the
      transitions between these two dynamical states as the temperature was increased.
      In the present work, we find the range of amplitudes of the drive field over
      which the dynamical states could be observed in a sinusoidal potential. The
      variation of the relative stability of the dynamical states as a function of
      drive-field amplitude is clarified by analyzing the nature of curves
      characterizing the stochastic resonance as the amplitude is varied within the
      range. 

PMID- 24125250
TI  - Perpetual extraction of work from a nonequilibrium dynamical system under
      Markovian feedback control.
AB  - By treating both control parameters and dynamical variables as probabilistic
      variables, we develop a succinct theory of perpetual extraction of work from a
      generic classical nonequilibrium system subject to a heat bath via repeated
      measurements under a Markovian feedback control. It is demonstrated that a
      problem for perpetual extraction of work in a nonequilibrium system is reduced to
      a problem of Markov chain in the higher-dimensional phase space. We derive a
      version of the detailed fluctuation theorem, which was originally derived for
      classical nonequilibrium systems by Horowitz and Vaikuntanathan [Phys. Rev. E 82,
      061120 (2010)], in a form suitable for the analyses of perpetual extraction of
      work. Since our theory is formulated for generic dynamics of probability
      distribution function in phase space, its application to a physical system is
      straightforward. As simple applications of the theory, two exactly solvable
      models are analyzed. The one is a nonequilibrium two-state system and the other
      is a particle confined to a one-dimensional harmonic potential in thermal
      equilibrium. For the former example, it is demonstrated that the observer on the
      transitory steps to the stationary state can lose energy and that work larger
      than that achieved in the stationary state can be extracted. For the latter
      example, it is demonstrated that the optimal protocol for the extraction of work
      via repeated measurements can differ from that via a single measurement. The
      validity of our version of the detailed fluctuation theorem, which determines the
      upper bound of the expected work in the stationary state, is also confirmed for
      both examples. These observations provide useful insights into exploration for
      realistic modeling of a machine that extracts work from its environment. 

PMID- 24125251
TI  - Temperature-driven irreversible generalized Langevin equation can capture the
      nonequilibrium dynamics of two dissipated coupled oscillators.
AB  - Kawai and Komatsuzaki [J. Chem. Phys. 134, 114523 (2011)] recently derived the
      nonequilibrium generalized Langevin equation (GLE) for a nonstationary system
      using the projection operator technique. In the limit when the environment is
      slowly changing (that is, a quasi-equilibrium bath), it should reduce to the
      irreversible GLE approach (iGLE) [J. Chem. Phys. 111, 7701 (1999)]. Kawai and
      Komatsuzaki, however, found that the driven harmonic oscillator, an example of a
      nonequilibrium system does not obey the iGLE presumably because it did not quite
      satisfy the limiting conditions of the latter. Notwithstanding the lack of a
      massive quasi-equilibrium bath (one of the conditions under which the iGLE had
      been derived earlier), we found that the temperature-driven iGLE (T-iGLE) [J.
      Chem. Phys. 126, 244506 (2007)] can reproduce the nonequilibrium dynamics of a
      driven dissipated pair of harmonic oscillators. It requires a choice of the
      function representing the coupling between the oscillator coordinate and the bath
      and shows that the T-iGLE representation is consistent with the projection
      operator formalism if only dominant bath modes are taken into account. Moreover,
      we also show that the more readily applicable phenomenological iGLE model is
      recoverable from the Kawai and Komatsuzaki model beyond the adiabatic limit used
      in the original T-iGLE theory.

PMID- 24125252
TI  - Fluctuation theorems for quantum processes.
AB  - We present fluctuation theorems and moment generating function equalities for
      generalized thermodynamic observables and quantum dynamics described by
      completely positive trace preserving maps, with and without feedback control. Our
      results include the quantum Jarzynski equality and Crooks fluctuation theorem,
      and clarify the special role played by the thermodynamic work and thermal
      equilibrium states in previous studies. We show that for a specific class of
      generalized measurements, which include projective measurements, unitality
      replaces microreversibility as the condition for the physicality of the reverse
      process in our fluctuation theorems. We present an experimental application of
      our theory to the problem of extracting the system-bath coupling magnitude, which
      we do for a system of pairs of coupled superconducting flux qubits undergoing
      quantum annealing.

PMID- 24125253
TI  - Criticality in alternating layered Ising models. I. Effects of connectivity and
      proximity.
AB  - The specific heats of exactly solvable alternating layered planar Ising models
      with strips of width m_{1} lattice spacings and "strong" couplings J_{1}
      sandwiched between strips of width m_{2} and "weak" coupling J_{2}, have been
      studied numerically to investigate the effects of connectivity and proximity. We
      find that the enhancements of the specific heats of the strong layers and of the
      overall or "bulk" critical temperature T_{c}(J_{1},J_{2};m_{1},m_{2}) arising
      from the collective effects reflect the observations of Gasparini and co-workers
      in experiments on confined superfluid helium. Explicitly, we demonstrate that
      finite-size scaling holds in the vicinity of the upper limiting critical point
      T_{1c} (?J_{1}/k_{B}) and close to the corresponding lower critical limit T_{2c}
      (?J_{2}/k_{B}) when m_{1} and m_{2} increase. However, the residual enhancement,
      defined via appropriate subtractions of leading contributions from the total
      specific heat, is dominated (away from T_{1c} and T_{2c}) by a decay factor
      1/(m_{1}+m_{2}) arising from the seams (or boundaries) separating the strips;
      close to T_{1c} and T_{2c} the decay is slower by a factor lnm_{1} and lnm_{2},
      respectively.

PMID- 24125254
TI  - Criticality in alternating layered Ising models. II. Exact scaling theory.
AB  - Part I of this article studied the specific heats of planar alternating layered
      Ising models with strips of strong coupling J_{1} sandwiched between strips of
      weak coupling J_{2}, to illustrate qualitatively the effects of connectivity,
      proximity, and enhancement in analogy to those seen in extensive experiments on
      superfluid helium by Gasparini and co-workers. It was demonstrated graphically
      that finite-size scaling descriptions hold in a variety of temperature regions
      including in the vicinity of the two specific heat maxima. Here we provide exact
      theoretical analyses and asymptotics of the specific heat that support and
      confirm the graphical findings. Specifically, at the overall or bulk critical
      point, the anticipated (and always present) logarithmic singularity is shown to
      vanish exponentially fast as the width of the stronger strips increases.

PMID- 24125255
TI  - Intruder-induced asymmetry in compartmentalized granular gases.
AB  - The clustering behavior of a compartmentalized monodisperse granular gas with the
      addition of one heavy intruding particle is investigated experimentally.
      Depending on the number of particles, the presence of a heavy intruder leads to
      three population states: a homogeneous state, an expelled clustering state, and a
      fully clustering state. These states are found to be consistent with the
      clustering of a purely monodisperse granular gas in an asymmetric
      compartmentalized structure. We obtain an exact relation between the size of an
      intruder and the elevation of the compartment bottom. This relation quantifies
      the particle-expelling ability of a heavy intruder, and suggests that the one
      intruder system is a type of asymmetric system with an intruder-size-related
      asymmetrical index xi. Under the framework of the flux model, a xi-associated Xi
      function is proposed to quantitatively reproduce the experimental results. 

PMID- 24125256
TI  - Characterizing the rheology of fluidized granular matter.
AB  - In this study we characterize the rheology of fluidized granular matter subject
      to secondary forcing. Our approach consists of first fluidizing granular matter
      in a drum half filled with grains via simple rotation and then superimposing
      oscillatory shear perpendicular to the downhill flow direction. The response of
      the system is mostly linear, with a phase lag between the grain motion and the
      oscillatory forcing. The rheology of the system can be well characterized by the
      GDR MiDi model if the system is forced with slow oscillations. The model breaks
      down when the forcing time scale becomes comparable to the characteristic time
      for energy dissipation in the flow.

PMID- 24125257
TI  - Regime transitions of granular flow in a shear cell: a micromechanical study.
AB  - The regime transitions of granular flow in a model shear cell are investigated
      numerically with a stress-controlled boundary condition. The correlations between
      the elastically and kinetically scaled stresses and the packing fraction are
      examined, and two packing fractions (0.58 and 0.50) are identified for the
      quasistatic to intermediate and intermediate to inertial regime transitions. The
      profiles and structures of contact networks and force chains among particles in
      different flow regimes are investigated. It is shown that the connectivity
      (coordination number) among particles and the homogeneity in the shear flow
      increase as the system goes through the inertial, intermediate, and then
      quasistatic regimes, and there is only little variation in the internal structure
      after the system has entered the quasistatic regime. Short-range force chains
      start to appear in the inertial regime, which also depend on the magnitude of the
      shear rate. The percolation of system-spanning force chains through the whole
      system is a characteristic of the onset of the quasistatic regime, which happens
      at a packing fraction that is close to the glass transition, i.e., about random
      loose packing (0.58) but far below the isotropic quasistatic (athermal) jamming
      packing fraction of random close packing (0.64). The tails of the probability
      density distribution P(f) of the scaled normal contact forces for the flows in
      different regimes are quantified by a stretched exponential P(f)=exp(-cf^{n})
      with a remarkable finding that n ~ 1.1 may be a potential demarcation point
      separating the quasistatic regime and the inertial or intermediate regimes.

PMID- 24125258
TI  - Packing fraction of trimodal spheres with small size ratio: an analytical
      expression.
AB  - In previous papers analytical expressions were derived and validated for the
      packing fraction of bimodal hard spheres with small size ratio, applicable to
      ordered (crystalline) [H. J. H. Brouwers, Phys. Rev. E 76, 041304 (2007);H. J. H.
      Brouwers, Phys. Rev. E 78, 011303 (2008)] and disordered (random) packings [H. J.
      H. Brouwers, Phys. Rev. E 87, 032202 (2013)]. In the present paper the underlying
      statistical approach, based on counting the occurrences of uneven pairs, i.e.,
      the fraction of contacts between unequal spheres, is applied to trimodal
      discretely sized spheres. The packing of such ternary packings can be described
      by the same type of closed-form equation as the bimodal case. This equation
      contains the mean volume of the spheres and of the elementary cluster formed by
      these spheres; for crystalline arrangements this corresponds to the unit cell
      volume. The obtained compact analytical expression is compared with empirical
      packing data concerning random close packing of spheres, taken from the
      literature, comprising ternary binomial and geometric packings; good agreement is
      obtained. The presented approach is generalized to ordered and disordered
      packings of multimodal mixes.

PMID- 24125259
TI  - Erosion dynamics of a wet granular medium.
AB  - Liquid may give strong cohesion properties to a granular medium, and confer a
      solidlike behavior. We study the erosion of a fixed circular aggregate of wet
      granular matter subjected to a flow of dry grains inside a half-filled rotating
      drum. During the rotation, the dry grains flow around the fixed obstacle. We show
      that its diameter decreases linearly with time for low liquid content, as wet
      grains are pulled out of the aggregate. This erosion phenomenon is governed by
      the properties of the liquids. The erosion rate decreases exponentially with the
      surface tension while it depends on the viscosity to the power -1. We propose a
      model based on the force fluctuations arising inside the flow, explaining both
      dependencies: The capillary force acts as a threshold and the viscosity controls
      the erosion time scale. We also provide experiments using different flowing
      grains, confirming our model. 

PMID- 24125260
TI  - Flow-mediated coupling on projectiles falling within a superlight granular
      medium.
AB  - Interesting collective motion emerges when several heavy intruder disks fall in a
      loose packed, quasi-two-dimensional granular bed of extremely light grains [F.
      Pacheco-Vazquez and J. C. Ruiz-Suarez, Nat. Commun. 1, 123 (2010)]. In
      particular, when two disks impact side by side, they initially repel and then
      they attract each other until they finally stop. Here we perform experiments and
      discrete-element soft-particle simulations to determine the range of action and
      the origin of these attractive and repulsive flow-mediated forces. We find that
      (1) the drag force on the disks fluctuate with a characteristic length linked to
      force chains that build up and break; (2) the repulsive force is present when the
      separation of the intruder disks is less than 6 times the size of the grains of
      the granular bed, which is the size of an aperture that allows a continuous
      discharge flow from a container; (3) the attractive force has a range of action
      between 5 and 6 times the size of the intruder disks; and (4) attraction exists
      only when intruders move faster than 1 m/s. These results suggest that repulsion
      originates from jamming of grains between intruders, and it supports the idea
      that attraction could be due to a "granular pressure" drop in the region between
      intruders caused by a high flow velocity of grains: a Bernoulli-like effect.
      However, our results do not rule out other mechanisms of interaction, like
      fluctuation-induced forces.

PMID- 24125261
TI  - Evolution of grain contacts in a granular sample under creep and stress
      relaxation.
AB  - This article deals with the characterization, using an acoustic technique, of the
      mechanical behavior of a dry dense granular medium under quasistatic loading.
      Ultrasound propagation through the contact-force network supporting the external
      load offers a noninvasive probe of the viscoelastic properties of such
      heterogeneous media. First the response of a glass bead packing is studied in an
      oedometric configuration during creep and relaxation tests. Quasilogarithmic
      increases of sound velocities are found in both mechanical tests. A model based
      on the mechanics of microcontacts between rough grains adequately reproduces our
      experimental results, especially for the evolution of elastic modulus. Another
      main experimental finding is that collective grain rearrangements within the
      packing also play a crucial role at the early stage of creep and relaxation.

PMID- 24125262
TI  - Spinodal decomposition of a binary magnetic fluid confined to a surface.
AB  - In our previous work [J. Chem. Phys. 136, 024502 (2012)], we reported a demixing
      phase transition of a quasi-two-dimensional, binary Heisenberg fluid mixture
      driven by the ferromagnetic interactions of the magnetic species. Here, we
      present a theoretical study for the time-dependent coarsening occurring within
      the two-phase region in the density-concentration plane, also known as spinodal
      decomposition. Our investigations are based on dynamical density functional
      theory (DDFT). The particles in the mixture are modeled as Gaussian soft spheres
      on a two-dimensional surface, where one component carries a classical spin of
      Heisenberg type. To investigate the two-phase region, we first present a linear
      stability analysis with respect to small, harmonic density perturbations. Second,
      to capture nonlinear effects, we calculate time-dependent structure factors by
      combining DDFT with Percus' test particle method. For the growth of the average
      domain size l during spinodal decomposition with time t, we observe a power-law
      behavior l?t^{delta_{alpha}} with delta_{m}?0.333 for the magnetic species and
      delta_{n}?0.323 for the nonmagnetic species.

PMID- 24125263
TI  - Influence of nanoparticle size on the nonlinear optical properties of magnetite
      ferrofluids.
AB  - The nonlinear index of refraction (n_{2}) and the two-photon absorption
      coefficient (beta) of water-based ferrofluids made of magnetite nanocrystals of
      different sizes and with different coatings have been measured through the Z-scan
      technique, with ultrashort (femtoseconds) laser pulses. Their third-order
      susceptibility is calculated from the values of n_{2} and beta. The influence of
      different particles' coatings and sizes on these nonlinear optical properties are
      investigated. The values of n_{2} and beta depend more significantly on the
      nanoparticles' size than on the particular coating. We observe a decrease of beta
      as the nanoparticles' diameters decrease, although the optical gap is found to be
      the same for all samples. The results are interpreted considering modifications
      in the electronic orbital shape due to the particles' nanosize effect.

PMID- 24125264
TI  - Shear thickening of dense suspensions due to energy dissipation in lubrication
      layers between particles.
AB  - This paper deals with a theoretical study of the shear thickening effects in
      concentrated suspensions of non-Brownian particles. Our analysis shows that an
      increase of the shear rate of the suspension flow leads to a decrease of the mean
      thickness of the gaps between the nearest particles in dense suspensions. In
      turn, this leads to the growth of energy dissipation in these gaps, which means
      an increase of the suspension effective viscosity with the shear rate. 

PMID- 24125265
TI  - Non-Gaussian statistics for the motion of self-propelled Janus particles:
      experiment versus theory.
AB  - Spherical Janus particles are one of the most prominent examples for active
      Brownian objects. Here, we study the diffusiophoretic motion of such
      microswimmers in experiment and in theory. Three stages are found: simple
      Brownian motion at short times, superdiffusion at intermediate times, and finally
      diffusive behavior again at long times. These three regimes observed in the
      experiments are compared with a theoretical model for the Langevin dynamics of
      self-propelled particles with coupled translational and rotational motion.
      Besides the mean square displacement also higher displacement moments are
      addressed. In particular, theoretical predictions regarding the non-Gaussian
      behavior of self-propelled particles are verified in the experiments.
      Furthermore, the full displacement probability distribution is analyzed, where in
      agreement with Brownian dynamics simulations either an extremely broadened peak
      or a pronounced double-peak structure is found, depending on the experimental
      conditions.

PMID- 24125266
TI  - Lateral aggregation induced by magnetic perturbations in a magnetorheological
      fluid based on non-Brownian particles.
AB  - A study of lateral aggregation, induced by an oscillatory field, in a
      magnetorheological fluid based on non-Brownian magnetic particles is presented.
      We investigate the behavior of chains formed by the particles, due to the
      simultaneous application of a static magnetic field and a sinusoidal magnetic
      field transverse to each other. We show that the effective oscillating field
      enhances the aggregation process. We discuss this result in terms of an effective
      particle concentration induced by the oscillating field when chains oscillate
      angularly and sweep the area around them. The oscillating field produces a
      lateral aggregation similar to that observed in systems composed of Brownian
      particles which is induced by thermal fluctuations. We study the effect of the
      oscillating field on the angular amplitude described by single chains. It is
      observed that the angular amplitude decreases as the frequency of the oscillating
      field increases; we discuss this behavior numerically in terms of a simple model
      for this system. Lateral aggregation is studied in detail in isolated pairs of
      chains of equal length at several conditions of separation and displacement. From
      the results, a phase diagram is obtained showing the conditions under which
      aggregation is possible.

PMID- 24125267
TI  - Multiple transient memories in sheared suspensions: robustness, structure, and
      routes to plasticity.
AB  - Multiple transient memories, originally discovered in charge-density-wave
      conductors, are a remarkable and initially counterintuitive example of how a
      system can store information about its driving. In this class of memories, a
      system can learn multiple driving inputs, nearly all of which are eventually
      forgotten despite their continual input. If sufficient noise is present, the
      system regains plasticity so that it can continue to learn new memories
      indefinitely. Recently, Keim and Nagel [Phys. Rev. Lett. 107, 010603 (2011)]
      showed how multiple transient memories could be generalized to a generic driven
      disordered system with noise, giving as an example simulations of a simple model
      of a sheared non-Brownian suspension. Here, we further explore simulation models
      of suspensions under cyclic shear, focusing on three main themes: robustness,
      structure, and overdriving. We show that multiple transient memories are a robust
      feature independent of many details of the model. The steady-state spatial
      distribution of the particles is sensitive to the driving algorithm; nonetheless,
      the memory formation is independent of such a change in particle correlations.
      Finally, we demonstrate that overdriving provides another means for controlling
      memory formation and retention.

PMID- 24125268
TI  - Collective stringlike motion of semiflexible filamentous particles in columnar
      liquid crystalline phases.
AB  - We study, by means of Brownian dynamics simulations, heterogeneous dynamics in a
      dense columnar phase of monodisperse hard filamentous particles, and find that in
      a background of barely moving particles, some particles occasionally engage in a
      fast coherent string-type motion similar to what is observed in glassy states of
      isometric particles. This fast motion is triggered by the exchange of particles
      between two or more columns at different positions in the columns, which leads to
      sudden displacement of particles between these positions. The distribution of
      particle displacements shows a pronounced peak at one particle length. We perform
      our simulations with particles of different persistence lengths and find that for
      more flexible particles, the number of jump events increases. As the number of
      particles in the columns increases with system size for a given linear fraction
      of particles in the columns, the peak in the distribution becomes wider and, for
      sufficiently large systems, the peak disappears completely. This is associated
      with the increase in the magnitude of fluctuations in the motion of particles as
      the system size increases. Our simulation results explain recent experimental
      observations on single-particle motion in dense columnar phases in aqueous
      dispersions of filamentous virus particles. 

PMID- 24125269
TI  - Restricted diffusion of small probe particles in a laponite dispersion.
AB  - Evanescent wave microscopy is used to study the dynamics of probe particles
      inside a laponite suspension, when the size of the latex probes is of the order
      of the diameter of the laponite disks. A correlation procedure is introduced that
      allows us to study quantitatively the diffusion of small probes. For all studied
      sizes, the motion exhibits two modes: a fast relaxation mode and a slow
      relaxation mode. In the fast relaxation mode, the probes diffuse in a viscous
      medium, whose viscosity does not depend on the diameter of the probes and is
      slightly larger than the viscosity of water. Then, the diffusion of the particles
      is restricted over distances larger than their diameters, which increase when the
      particle diameter decreases. In this regime, the probe particles experience the
      elasticity of the solution and the apparent elastic modulus increases when the
      diameter of the probe particle increases, whereas for large enough particles, the
      macroscopic behavior is recovered, in which the diffusing particles experience a
      homogeneous medium, and the macroscopic elastic modulus is recovered. 

PMID- 24125270
TI  - Shear localization in three-dimensional amorphous solids.
AB  - In this paper we extend the recent theory of shear localization in two
      dimensional (2D) amorphous solids to three dimensions. In two dimensions the
      fundamental instability of shear localization is related to the appearance of a
      line of displacement quadrupoles that makes an angle of 45^{?} with the principal
      stress axis. In three dimensions the fundamental plastic instability is also
      explained by the formation of a lattice of anisotropic elastic inclusions. In the
      case of pure external shear stress, we demonstrate that this is a 2D triangular
      lattice of similar elementary events. It is shown that this lattice is arranged
      on a plane that, similarly to the 2D case, makes an angle of 45^{?} with the
      principal stress axis. This solution is energetically favorable only if the
      external strain exceeds a yield-strain value that is determined by the strain
      parameters of the elementary events and the Poisson ratio. The predictions of the
      theory are compared to numerical simulations and very good agreement is observed.

PMID- 24125271
TI  - Statistics of energy dissipation and stress relaxation in a crumpling network of
      randomly folded aluminum foils.
AB  - We study stress relaxation in hand folded aluminum foils subjected to the
      uniaxial compression force F(lambda). We found that once the compression ratio is
      fixed (lambda=const) the compression force decreases in time as F?F_{0}P(t),
      where P(t) is the survival probability time distribution belonging to the domain
      of attraction of max-stable distribution of the Frechet type. This finding
      provides a general physical picture of energy dissipation in the crumpling
      network of a crushed elastoplastic foil. The difference between energy
      dissipation statistics in crushed viscoelastic papers and elastoplastic foils is
      outlined. Specifically, we argue that the dissipation of elastic energy in
      crushed aluminum foils is ruled by a multiplicative Poisson process governed by
      the maximum waiting time distribution. The mapping of this process into the
      problem of transient random walk on a fractal crumpling network is suggested.

PMID- 24125272
TI  - Relaxation of a family of broken-bond crystal-surface models.
AB  - We study the continuum limit of a family of kinetic Monte Carlo models of crystal
      surface relaxation that includes both the solid-on-solid and discrete Gaussian
      models. With computational experiments and theoretical arguments we are able to
      derive several partial differential equation limits identified (or nearly
      identified) in previous studies and to clarify the correct choice of surface
      tension appearing in the PDE and the correct scaling regime giving rise to each
      PDE. We also provide preliminary computational investigations of a number of
      interesting qualitative features of the large-scale behavior of the models. 

PMID- 24125273
TI  - Pore-scale dynamics of salt precipitation in drying porous media.
AB  - We study the pore-scale dynamics of salt precipitation in three-dimensional
      drying porous media, utilizing high resolution x-ray microtomography and scanning
      electron microscopy. Our results illustrate that the salt precipitation patterns
      in drying porous media are nonuniform, manifesting the influence of the spatial
      distribution of pore sizes on the dynamics of salt crystallization and formation
      of discrete efflorescence. Results reveal that during stage-1 evaporation from
      saline porous media, the salt precipitation rate initially increases which is
      followed by a constant precipitation rate. This non-linear behaviour is
      attributed to the preferential liquid vaporization and salt precipitation in
      finer pores located at the surface of the porous medium contributing in
      evaporation according to the pore sizes. We also show that, contrary to common
      practice, the macroscopic convection-diffusion equation cannot provide accurate
      predictions for the dynamics of salt precipitation, at least at the early stages,
      due to the microscale heterogeneity of evaporation sites at the surface that
      results in salt precipitation exclusively in the finer pores. 

PMID- 24125274
TI  - Tearing of free-standing graphene.
AB  - We examine the fracture mechanics of tearing graphene. We present a molecular
      dynamics simulation of the propagation of cracks in clamped, free-standing
      graphene as a function of the out-of-plane force. The geometry is motivated by
      experimental configurations that expose graphene sheets to out-of-plane forces,
      such as back-gate voltage. We establish the geometry and basic energetics of
      failure and obtain approximate analytical expressions for critical crack lengths
      and forces. We also propose a method to obtain graphene's toughness. We observe
      that the cracks' path and the edge structure produced are dependent on the
      initial crack length. This work may help avoid the tearing of graphene sheets and
      aid the production of samples with specific edge structures. 

PMID- 24125275
TI  - Modeling of electrode polarization for electrolytic cells with a limited ionic
      adsorption.
AB  - Dilute electrolytic cells filled with chlorobenzene containing small amounts of
      tetrabutylammonium tetraphenylborate show anomalous dielectric dispersions in low
      frequency regions. We propose a new model for electrode polarization in order to
      analyze the dielectric behavior of the dilute electrolytic cells. The model
      comprises two capacitive components: One is the space-charge polarization
      accompanied with a specific ionic adsorption on electrodes, and the other is the
      electrode capacitance which is brought about by an electronic spillover from the
      electrode surface. This model can primarily explain the anomalous frequency
      dependent dielectric behavior of the electrolytic cells not only with low
      electrolyte concentrations, but also with high concentrations and can correctly
      describe the characteristics of the electrode polarization reflected in the
      dielectric spectra. 

PMID- 24125276
TI  - Phase-field-crystal model for magnetocrystalline interactions in isotropic
      ferromagnetic solids.
AB  - An isotropic magnetoelastic phase-field-crystal model to study the relation
      between morphological structure and magnetic properties of pure ferromagnetic
      solids is introduced. Analytic calculations in two dimensions were used to
      determine the phase diagram and obtain the relationship between elastic strains
      and magnetization. Time-dependent numerical simulations in two dimensions were
      used to demonstrate the effect of grain boundaries on the formation of magnetic
      domains. It was shown that the grain boundaries act as nucleating sites for
      domains of reverse magnetization. Finally, we derive a relation for coercivity
      versus grain misorientation in the isotropic limit.

PMID- 24125277
TI  - Partial slip in mesoscale contacts: dependence on contact size.
AB  - Using acoustic resonators, we have studied the occurrence and the magnitude of
      partial slip between glass spheres and polymer surfaces. The measurement relies
      on the shifts of resonance frequency and bandwidth, Deltaf and DeltaGamma,
      induced by the contact as well as the dependence of Deltaf and DeltaGamma on the
      amplitude of oscillation. One often finds a decrease of Deltaf at elevated
      amplitudes, which goes back to partial slip (also "microslip"). Building on two
      different models of partial slip, we derive the frequency-amplitude relation from
      the force-displacement relation. In accordance with both models, the bandwidth is
      found to increase with amplitude in the partial slip regime. For the highest
      amplitudes and largest spheres investigated, one observes a decrease of bandwidth
      with amplitude, which is interpreted as a transition to gross slip. Deviating
      from both models of partial slip, Deltaf is sometimes found to be independent of
      amplitude in the low-amplitude range. Constant Deltaf implies linear force
      displacement relations. The critical amplitude for the onset of partial slip
      depends on the contact radius, where partial slip is more pronounced for larger
      contacts. This finding can be explained by a smooth stress profile at the edge of
      the contact with no singularity. The stress at the edge might be lowered by
      nanoscale roughness, by capillary forces, or by the inability of the two surfaces
      to reestablish a sticking contact at the turning point of the oscillation.

PMID- 24125278
TI  - Localization and length-scale doubling in disordered films on soft substrates.
AB  - Wrinkling and folding are examined experimentally for three distinct types of
      disordered films on polydimethylsiloxane (PDMS) substrates; diblock copolymers,
      glassy polymers, and single-wall carbon nanotubes. All three of these systems
      exhibit localization and length-scale doubling at small strains, and we
      qualitatively account for these observations with a simple physical argument
      related to the width of the stress correlation function and the interaction of
      localization sites. Our results have relevance to wrinkling and folding in a
      diverse array of disordered films on soft substrates, and the insights offered
      here should help guide the development of theoretical models for the influence of
      structural disorder on thin-film wrinkling instabilities. 

PMID- 24125279
TI  - Acousto-optic effect in nematic liquid crystals: experimental evidence of an
      elastic regime.
AB  - We show that the experimental data for the action of ultrasonic waves on
      homeotropically aligned nematic-liquid-crystal cells reported by Kapustina, in
      Akust. Zh. 54, 900 (2008) [Acoust. Phys. 54, 778 (2008)] can be explained in the
      framework of the director-density coupling theory in the regime of low acoustic
      intensity. This result therefore provides support for the hypothesis that the
      interaction between sound and nematic liquid crystals is dominated by an elastic
      energy.

PMID- 24125280
TI  - Calamitic and antinematic orientational order produced by the generalized Straley
      lattice model.
AB  - We consider here a classical model, consisting of D_{2h}-symmetric particles in a
      three-dimensional simple-cubic lattice; the pair potential is isotropic in
      orientation space, and restricted to nearest neighbors. The simplest potential
      model is written in terms of the squares of the scalar products between unit
      vectors describing the three interacting arms of the molecules, as proposed in
      previous literature. Two predominant antinematic couplings of equal strength (+1)
      are perturbed by a comparatively weaker calamitic one, parameterized by a
      coupling constant -z ranging in [-1,0]. This choice rules out thermodynamically
      stable phases endowed with macroscopic biaxiality. The antinematic terms favor
      states with the corresponding molecular axes mutually orthogonal. Although the
      low-temperature phase of the special case with null calamitic term (PP0) is
      uniaxial and antinematically ordered, in the general case presented here both
      Monte Carlo and molecular-field approaches show that, for z close to zero, the
      models exhibit a low-temperature uniaxial nematic phase, followed by an
      antinematic one, and finally by the orientationally disordered one. On the other
      hand, for sufficiently large values of z, we only find evidence of uniaxial
      calamitic behavior, as expected by following the limiting cases.

PMID- 24125281
TI  - Effect of cybotactic clusters on the elastic and flexoelectric properties of bent
      core liquid crystals belonging to the same homologous series.
AB  - We report results of the splay (K_{11}) and bend (K_{33}) elastic constants and
      the effective flexoelectric coefficient of three bent-core liquid crystals
      belonging to a homologous series of 4-cyanoresorcinol bisbenzoates with varying
      chain lengths. Based on the results of x-ray scattering studies, one of the three
      compounds with a shorter chain length (C4) has few, if any, clusters present in
      its nematic phase and behaves quite normally, whereas the others two with longer
      chain lengths (C6 and C7) show the presence of cybotactic nematic phase with
      smectic C type clusters. These grow in size with a reduction in temperature.
      K_{33} is found to be the least for C7, whereas it is weakly dependent on
      temperature. K_{33} is somewhat higher for C4 and C6 and is almost independent of
      temperature. K_{11} for C6 and C7 is higher by 20% to 50% than C4 depending on
      the temperature. K_{11} increases linearly with a reduction in temperature for
      the three compounds. For C6 K_{11}>K_{33} by a factor up to ~2 depending on the
      temperature, for C4 it is greater by a factor up to 1.3, and for C7 it is greater
      by a factor of ~2.5. These results suggest that the clusters do not have any
      effect on K_{11}. The magnitude of the effective flexoelectric coefficient
      e=(|e_{1}-e_{3}|) is measured by creating a uniform lying helix (ULH)
      configuration in a planar cell. By doping the bent-core system with a small wt%
      of a chiral dopant, the ULH is obtained by cooling planar cells to the
      cholesteric phase under weak electric field. The effective flexoelectric
      coefficient is greater for the bent-core systems than for calamatics but it is
      much lower than would otherwise have been expected for such systems. |e_{1}
      e_{3}| for C4 > C6 ~ C7 is greater by 20% to 25% than C6 and C7 at the same
      reduced temperature. These differences in the effective flexoelectric coefficient
      can easily arise from a difference in the chain lengths among the members of the
      series but if the presence of clusters were to have an influence on |e_{1}
      e_{3}|, then these would reduce it, contrary to the expectations for the bent
      core systems.

PMID- 24125282
TI  - CdSe nanoparticles dispersed in ferroelectric smectic liquid crystals: effects
      upon the smectic order and the smectic-A to chiral smectic-C phase transition.
AB  - Spherical CdSe nanoparticles, surface-treated with oleylamine and tri
      octylphosphine, dispersed in ferroelectric liquid crystals, can efficiently
      target disclination lines, substantially altering the macroscopic properties of
      the host compound. Here we present an ac calorimetry and x-ray diffraction study
      demonstrating that for a large range of nanoparticle concentrations the smectic-A
      layer thickness increases monotonically. This provides evidence for enhanced
      accumulation of nanoparticles at the smectic layers. Our results for the Smectic
      A (SmA) to chiral smectic-C (SmC) phase transition of the liquid crystal S-(+)4
      (2'-methylbutyl)phenyl-4'-n-octylbiphenyl-4-carboxylate (CE8) reveal that the
      character of the transition is profoundly changed as a function of the
      nanoparticle concentration. Large transition temperature shifts are recorded.
      Moreover, the heat-capacity peaks exhibit a crossover trend to a step-like
      anomaly. This behavior may be linked to the weakening of the SmA and SmC order
      parameter coupling responsible for the observed near-tricritical, mean-field
      character of the transition in bulk CE8. At lower temperatures, the presence of
      nanoparticles disrupts the phase sequence involving the tilted hexatic phases
      most likely by obstructing the establishment of long-range bond-orientational
      order.

PMID- 24125283
TI  - Cholesteric-nematic transition in an asymmetric strong-weak anchoring cell.
AB  - We discuss the cholesteric-nematic transition induced by an external field in a
      cell in the shape of a slab of finite thickness whose anchoring energy is
      infinitely strong on one surface and negligible on the other. The case where the
      surface orientations of the cholesteric director are parallel in the ground state
      is considered. In a sample of thickness l, multiple of the natural periodicity of
      the system Lambda, the number of complete twists in the cholesteric liquid
      crystal is reduced by increasing the strength of the external distorting field.
      The sequence of the field values for expelling complete twists accumulate as the
      strength of the field approaches a critical value. Beyond this critical value the
      system assumes an unwinding configuration going toward a uniform structure,
      corresponding to nematic phase. Generalization of the results to the weak-weak
      anchoring cell case is also discussed. In our analysis the anisotropic part of
      the surface energy is assumed or very large or very small with respect to the
      total energy per unit surface due to the bulk distortion induced by the magnetic
      field. 

PMID- 24125284
TI  - Liquid-crystal patterns of rectangular particles in a square nanocavity.
AB  - Using density-functional theory in the restricted-orientation approximation, we
      analyze the liquid-crystal patterns and phase behavior of a fluid of hard
      rectangular particles confined in a two-dimensional square nanocavity of side
      length H composed of hard inner walls. Patterning in the cavity is governed by
      surface-induced order as well as capillary and frustration effects and depends on
      the relative values of the particle aspect ratio kappa=L/sigma, with L the length
      and sigma the width of the rectangles (L>=sigma), and cavity size H. Ordering may
      be very different from bulk (H->infinity) behavior when H is a few times the
      particle length L (nanocavity). Bulk and confinement properties are obtained for
      the cases kappa=1, 3, and 6. In bulk the isotropic phase is always stable at low
      packing fractions eta=Lsigmarho_{0} (with rho_{0} the average density) and
      nematic, smectic, columnar, and crystal phases can be stabilized at higher eta
      depending on kappa: For increasing eta the sequence of isotropic to columnar is
      obtained for kappa=1 and 3, whereas for kappa=6 we obtain isotropic to nematic to
      smectic (the crystal being unstable in all three cases for the density range
      explored). In the confined fluid surface-induced frustration leads to fourfold
      symmetry breaking in all phases (which become twofold symmetric). Since no
      director distortion can arise in our model by construction, frustration in the
      director orientation is relaxed by the creation of domain walls (where the
      director changes by 90^{?}); this configuration is necessary to stabilize
      periodic phases. For kappa=1 the crystal becomes stable with commensurate
      transitions taking place as H is varied. These transitions involve structures
      with different number of peaks in the local density. In the case kappa=3 the
      commensurate transitions involve columnar phases with different number of
      columns. In the case kappa=6 the high-density region of the phase diagram is
      dominated by commensurate transitions between smectic structures; at lower
      densities there is a symmetry-breaking isotropic to nematic transition exhibiting
      nonmonotonic behavior with cavity size. Apart from the present application in a
      confinement setup, our model could be used to explore the bulk region near close
      packing in order to elucidate the possible existence of disordered phases at
      close packing.

PMID- 24125285
TI  - Octupolar approximation for the excluded volume of axially symmetric convex
      bodies.
AB  - We propose a simply computable formula for the excluded volume of convex, axially
      symmetric bodies, based on the classical Brunn-Minkoski theory for convex bodies,
      which is briefly outlined in an Appendix written in a modern mathematical
      language. This formula is applied to cones and spherocones, which are regularized
      cones; a shape-reconstruction algorithm is able to generate the region in space
      inaccessible to them and to compute their excluded volume, which is found to be
      in good agreement with our approximate analytical formula. Finally, for
      spherocones with an appropriately tuned amplitude, we predict the occurrence of a
      relative deep minimum of the excluded volume in a configuration lying between the
      parallel alignment (where the excluded volume is maximum) and the antiparallel
      alignment (where the excluded volume is minimum). 

PMID- 24125286
TI  - Distribution of glass transition temperature in multilayered poly(methyl
      methacrylate) thin film supported on a Si substrate as studied by neutron
      reflectivity.
AB  - We studied the distribution of glass transition temperature (Tg) through neutron
      reflectivity in a poly(methyl methacrylate) (PMMA) thin film supported on a
      silicon substrate with a five-layered PMMA thin film consisting of deuterated
      PMMA and hydrogenated-PMMA. The depth distribution of Tg was successfully
      observed in the PMMA thin film. Compared to the previously reported distribution
      of Tg in a polystyrene thin film, the presence of a long-range interfacial
      effect, supposedly caused by an interaction between PMMA and the substrate, is
      considered to be responsible for the differences in both the distribution of Tg
      and the thickness dependence of Tg in both polymers. Therefore, it is expected
      that the thickness dependence of Tg reported for single-layered polymer thin
      films can, in principle, be understood from the viewpoint of the difference in
      the depth distribution of Tg.

PMID- 24125287
TI  - Dynamical crossover between hyperdiffusion and subdiffusion of polymer-grafted
      nanoparticles in a polymer matrix.
AB  - The dynamical behavior of polystyrene-grafted silica nanoparticles dispersed in
      an atactic polystyrene matrix was studied using x-ray photon correlation
      spectroscopy. The time-autocorrelation functions were subjected to fitting
      analyses based on continuous-time random walk models. The nanoparticles exhibited
      non-Brownian behavior, and as the temperature increased, the crossover from
      hyperdiffusion to subdiffusion occurred at 1.25T_{g}, where T_{g} is the glass
      transition temperature of the matrix polystyrene. Hyperdiffusive behavior is
      caused by the dynamical heterogeneity of the polymer matrix associated with the
      glass transition. When the temperature was higher than 1.25T_{g}, the interaction
      of the grafted polymers with the polymer matrix became relatively significant,
      and caused a dramatic change in the dynamical behavior of the nanoparticles.

PMID- 24125288
TI  - Elasticity of cross-linked semiflexible biopolymers under tension.
AB  - Aiming at the mechanical properties of cross-linked biopolymers, we set up and
      analyze a model of two weakly bending wormlike chains subjected to a tensile
      force, with regularly spaced inter-chain bonds (cross-links) represented by
      harmonic springs. Within this model, we compute the force-extension curve and the
      differential stiffness exactly and discuss several limiting cases. Cross-links
      effectively stiffen the chain pair by reducing thermal fluctuations transverse to
      the force and alignment direction. The extra alignment due to cross-links
      increases both with growing number and with growing strength of the cross-links,
      and is most prominent for small force f. For large f, the additional, cross-link
      induced extension is subdominant except for the case of linking the chains
      rigidly and continuously along their contour. In this combined limit, we recover
      asymptotically the elasticity of a weakly bending wormlike chain without
      constraints, stiffened by a factor of 4. The increase in differential stiffness
      can be as large as 100% for small f or large numbers of cross-links. 

PMID- 24125289
TI  - Linear surface roughness growth and flow smoothening in a three-dimensional
      biofilm model.
AB  - The sessile microbial communities known as biofilms exhibit varying architectures
      as environmental factors are varied, which for immersed biofilms includes the
      shear rate of the surrounding flow. Here we modify an established agent-based
      biofilm model to include affine flow and employ it to analyze the growth of
      surface roughness of single-species, three-dimensional biofilms. We find linear
      growth laws for surface geometry in both horizontal and vertical directions and
      measure the thickness of the active surface layer, which is shown to
      anticorrelate with roughness. Flow is shown to monotonically reduce surface
      roughness without affecting the thickness of the active layer. We argue that the
      rapid roughening is due to nonlocal surface interactions mediated by the nutrient
      field, which are curtailed when advection competes with diffusion. We further
      argue the need for simplified models to elucidate the underlying mechanisms
      coupling flow to growth.

PMID- 24125290
TI  - Estimating the hyperfine coupling parameters of the avian compass by
      comprehensively considering the available experimental results.
AB  - Migratory birds can utilize the geomagnetic field for orientation and navigation
      through a widely accepted radical-pair mechanism. Although many theoretical works
      have been done, the available experimental results have not been fully
      considered, especially the temporary disorientation induced by the field which is
      increased by 30% of the geomagnetic field and the disorientation of the very weak
      resonant field of 15 nT. In this paper, we consider the monotonicity of the
      singlet yield angular profile as the prerequisite of direction sensitivity, and
      find that for some optimal values of the hyperfine coupling parameters (that is,
      the order of 10^{-7}~10^{-6} meV) the experimental results available so far can
      be satisfied. We also investigate the effects of two decoherence environments and
      demonstrate that, in order to satisfy the available experimental results, the
      decoherence rate should be lower than the recombination rate. Finally, we
      investigate the effects of the fluctuating magnetic noises and find that the
      vertical noise destroys the monotonicity of the profile completely, but the
      parallel noise preserves the monotonicity perfectly and even can enhance the
      direction sensitivity.

PMID- 24125291
TI  - Modeling biological tissue growth: discrete to continuum representations.
AB  - There is much interest in building deterministic continuum models from discrete
      agent-based models governed by local stochastic rules where an agent represents a
      biological cell. In developmental biology, cells are able to move and undergo
      cell division on and within growing tissues. A growing tissue is itself made up
      of cells which undergo cell division, thereby providing a significant transport
      mechanism for other cells within it. We develop a discrete agent-based model
      where domain agents represent tissue cells. Each agent has the ability to undergo
      a proliferation event whereby an additional domain agent is incorporated into the
      lattice. If a probability distribution describes the waiting times between
      proliferation events for an individual agent, then the total length of the domain
      is a random variable. The average behavior of these stochastically proliferating
      agents defining the growing lattice is determined in terms of a Fokker-Planck
      equation, with an advection and diffusion term. The diffusion term differs from
      the one obtained Landman and Binder [J. Theor. Biol. 259, 541 (2009)] when the
      rate of growth of the domain is specified, but the choice of agents is random.
      This discrepancy is reconciled by determining a discrete-time master equation for
      this process and an associated asymmetric nonexclusion random walk, together with
      consideration of synchronous and asynchronous updating schemes. All theoretical
      results are confirmed with numerical simulations. This study furthers our
      understanding of the relationship between agent-based rules, their
      implementation, and their associated partial differential equations. Since tissue
      growth is a significant cellular transport mechanism during embryonic growth, it
      is important to use the correct partial differential equation description when
      combining with other cellular functions. 

PMID- 24125292
TI  - Anomalous diffusion of proteins in sheared lipid membranes.
AB  - We use coarse grained molecular dynamics simulations to investigate diffusion
      properties of sheared lipid membranes with embedded transmembrane proteins. In
      membranes without proteins, we find normal in-plane diffusion of lipids in all
      flow conditions. Protein embedded membranes behave quite differently: by imposing
      a simple shear flow and sliding the monolayers of the membrane over each other,
      the motion of protein clusters becomes strongly superdiffusive in the shear
      direction. In such a circumstance, the subdiffusion regime is predominant
      perpendicular to the flow. We show that superdiffusion is a result of accelerated
      chaotic motions of protein-lipid complexes within the membrane voids, which are
      generated by hydrophobic mismatch or the transport of lipids by proteins.

PMID- 24125293
TI  - Genus distribution and thermodynamics of a random matrix model of RNA with Penner
      interaction.
AB  - The nonlinear Penner external interaction is introduced and studied in the random
      matrix model of homo RNA. A numerical technique is developed to study the
      partition function, and a general formula is obtained for all lengths. The genus
      distribution function for the system is obtained, plotted, and compared with the
      genus distribution for the real RNA structures found from the protein databank.
      The genus distribution shows that the nonlinear interaction favors the formation
      of low genus structures and matches the result for real RNA structures. The
      distribution of structure with temperature suggests that nonlinear interaction is
      biased toward the planar structures. The variation of chemical potential with
      temperature and interaction strength indicates the presence of additional
      molecules in the system other than the magnesium ions and possibly represents a
      phase transition. The specific heat has a bump and its derivatives shows a double
      peak behavior at a particular temperature. On analyzing the specific heat and
      derivatives for each genus separately, the planar structure (genus zero) is shown
      to contribute the most to the bump and double peak. This observation in the
      nonlinear model is similar to that observed in the unfolding experiments on RNA. 

PMID- 24125294
TI  - Energetic pulses in exciton-phonon molecular chains and conservative numerical
      methods for quasilinear Hamiltonian systems.
AB  - The phenomenon of coherent energetic pulse propagation in exciton-phonon
      molecular chains such as alpha-helix protein is studied using an ODE system model
      of Davydov-Scott type, both with numerical studies using a new unconditionally
      stable fourth-order accurate energy-momentum conserving time discretization and
      with analytical explanation of the main numerical observations. Impulsive initial
      data associated with initial excitation of a single amide-I vibration by the
      energy released by ATP hydrolysis are used as well as the best current estimates
      of physical parameter values. In contrast to previous studies based on a proposed
      long-wave approximation by the nonlinear Schrodinger (NLS) equation and focusing
      on initial data resembling the soliton solutions of that equation, the results
      here instead lead to approximation by the third derivative nonlinear Schrodinger
      equation, giving a far better fit to observed behavior. A good part of the
      behavior is indeed explained well by the linear part of that equation, the Airy
      PDE, while other significant features do not fit any PDE approximation but are
      instead explained well by a linearized analysis of the ODE system. A convenient
      method is described for construction of the highly stable, accurate conservative
      time discretizations used, with proof of its desirable properties for a large
      class of Hamiltonian systems, including a variety of molecular models.

PMID- 24125295
TI  - Hybrid lipids increase nanoscale fluctuation lifetimes in mixed membranes.
AB  - A recently proposed ternary mixture model is used to predict fluctuation domain
      lifetimes in the one phase region. The membrane is made of saturated,
      unsaturated, and hybrid lipids that have one saturated and one unsaturated
      hydrocarbon chain. The hybrid lipid is a natural linactant which can reduce the
      packing incompatibility between saturated and unsaturated lipids. The fluctuation
      lifetimes are predicted as a function of the hybrid lipid fraction and the
      fluctuation domain size. These lifetimes can be increased by up to three orders
      of magnitude compared to the case of no hybrids. With hybrid, small length scale
      fluctuations have sizable amplitudes even close to the critical temperature and,
      hence, benefit from enhanced critical slowing down. The increase in lifetime is
      particularly important for nanometer scale fluctuation domains where the hybrid
      orientation and the other lipids composition are highly coupled.

PMID- 24125296
TI  - Cellular polarization: interaction between extrinsic bounded noises and the wave
      pinning mechanism.
AB  - Cell polarization (cued or uncued) is a fundamental mechanism in cell biology. As
      an alternative to the classical Turing bifurcation, it has been proposed that the
      onset of cell polarity might arise by means of the well-known phenomenon of wave
      pinning [Gamba et al., Proc. Natl. Acad. Sci. USA 102, 16927 (2005)]. A
      particularly simple and elegant deterministic model of cell polarization based on
      the wave-pinning mechanism has been proposed by Edelstein-Keshet and coworkers
      [Biophys. J. 94, 3684 (2008)]. This model consists of a small biomolecular
      network where an active membrane-bound factor interconverts into its inactive
      form that freely diffuses in the cell cytosol. However, biomolecular networks do
      communicate with other networks as well as with the external world. Thus, their
      dynamics must be considered as perturbed by extrinsic noises. These noises may
      have both a spatial and a temporal correlation, and in any case they must be
      bounded to preserve the biological meaningfulness of the perturbed parameters.
      Here we numerically show that the inclusion of external spatiotemporal bounded
      parametric perturbations in the above wave-pinning-based model of cellular
      polarization may sometimes destroy the polarized state. The polarization loss
      depends on both the extent of temporal and spatial correlations and on the kind
      of noise employed. For example, an increase of the spatial correlation of the
      noise induces an increase of the probability of cell polarization. However, if
      the noise is spatially homogeneous then the polarization is lost in the majority
      of cases. These phenomena are independent of the type of noise. Conversely, an
      increase of the temporal autocorrelation of the noise induces an effect that
      depends on the model of noise.

PMID- 24125297
TI  - Nonicosahedral pathways for capsid expansion.
AB  - For a significant number of viruses a structural transition of the protein
      container that encapsulates the viral genome forms an important part of the life
      cycle and is a prerequisite for the particle becoming infectious. Despite many
      recent efforts the mechanism of this process is still not fully understood, and a
      complete characterization of the expansion pathways is still lacking. We present
      here a coarse-grained model that captures the essential features of the expansion
      process and allows us to investigate the conditions under which a viral capsid
      becomes unstable. Based on this model we demonstrate that the structural
      transitions in icosahedral viral capsids are likely to occur through a low
      symmetry cascade of local expansion events spreading in a wavelike manner over
      the capsid surface. 

PMID- 24125298
TI  - Stable and flexible system for glucose homeostasis.
AB  - Pancreatic islets, controlling glucose homeostasis, consist of alpha, beta, and
      delta cells. It has been observed that alpha and beta cells generate out-of-phase
      synchronization in the release of glucagon and insulin, counter-regulatory
      hormones for increasing and decreasing glucose levels, while beta and delta cells
      produce in-phase synchronization in the release of the insulin and somatostatin.
      Pieces of interactions between the islet cells have been observed for a long
      time, although their physiological role as a whole has not been explored yet. We
      model the synchronized hormone pulses of islets with coupled phase oscillators
      that incorporate the observed cellular interactions. The integrated model shows
      that the interaction from beta to delta cells, of which sign is a subject of
      controversy, should be positive to reproduce the in-phase synchronization between
      beta and delta cells. The model also suggests that delta cells help the islet
      system flexibly respond to changes of glucose environment. 

PMID- 24125299
TI  - Critical bending torque of DNA is a materials parameter independent of local base
      sequence.
AB  - Short double-stranded DNA molecules exhibit a softening transition under large
      bending which is quantitatively described by a critical bending torque tau_{c} at
      which the molecule develops a kink. Through equilibrium measurements of the
      elastic energy of short (~10 nm), highly stressed DNA molecules with a nick at
      the center we determine tau_{c} for different sequences around the nick. We find
      that tau_{c} is a robust materials parameter essentially independent of sequence.
      The measurements also show that, at least for nicked DNA, the local structure at
      the origin of the softening transition is not a single-stranded "bubble."

PMID- 24125300
TI  - Perturbative solution to susceptible-infected-susceptible epidemics on networks.
AB  - Herein we provide a closed form perturbative solution to a general M-node network
      susceptible-infected-susceptible (SIS) model using the transport rates between
      nodes as a perturbation parameter. We separate the dynamics into a short-time
      regime and a medium-to-long-time regime. We solve the short-time dynamics of the
      system and provide a limit before which our explicit, analytical result of the
      first-order perturbation for the medium-to-long-time regime is to be employed.
      These stitched calculations provide an approximation to the full temporal
      dynamics for rather general initial conditions. To further corroborate our
      results, we solve the mean-field equations numerically for an infectious SIS
      outbreak in New Zealand (NZ, Aotearoa) recomposed into 23 subpopulations where
      the virus is spread to different subpopulations via (documented) air traffic
      data, and the country is internationally quarantined. We demonstrate that our
      analytical predictions compare well to the numerical solution.

PMID- 24125301
TI  - Bistability in a stochastic RNA-mediated gene network.
AB  - Small regulatory RNAs (srRNAs) are important regulators of gene expression in
      eukaryotes and prokaryotes. A common motif containing srRNA is a bistable two
      gene motif where one gene codes for a transcription factor (TF) which represses
      the transcription of the second gene, whose transcript is a srRNA which targets
      the first gene's transcript. Here, we investigate the properties of this motif in
      a stochastic model which takes the low copy numbers of the RNA components into
      account. First, we examine the conditions for stability of the two "noisy
      attractors." We find that for realistic low copy numbers, extreme, but within
      realistic intervals, mutual repression strengths are required to compensate for
      the variability of the RNA numbers and thus, achieve long-term bistability.
      Second, the promoter initiation kinetics is found to strongly influence the
      bistability of the switch. Super-Poissonian RNA production disrupts the ability
      of the srRNA to silence its target, though sub-Poissonian RNA production does not
      rule out the need for strong mutual repression. Finally, we show that asymmetry
      between the two interactions forming the switch allows an external input to
      induce the transition from "high srRNA" to "'high TF" more easily (i.e., with a
      shorter input) than in the opposite direction. We hypothesize that this
      asymmetric switching property allows these circuits to be more sensitive to one
      external input, without sacrificing the stability of one of the noisy attractors.

PMID- 24125302
TI  - Conformational change induced by electron transfer in a monolayer of cytochrome
      P450 reductase adsorbed at the Au(110)-phosphate buffer interface.
AB  - The reflection anisotropy spectroscopy profiles of a variant of cytochrome P450
      reductase adsorbed at the Au(110)-phosphate buffer interface depend on the
      sequence of potentials applied to the Au(110) electrode. It is suggested that
      this dependence arises from changes in the orientation of the isoalloxazine ring
      structures in the protein with respect to the Au(110) surface. This offers a
      method of monitoring conformational change in this protein by measuring
      variations in the reflection anisotropy spectrum arising from changes in the
      redox potential. 

PMID- 24125303
TI  - Quantification of noise in bifunctionality-induced post-translational
      modification.
AB  - We present a generic analytical scheme for the quantification of fluctuations due
      to bifunctionality-induced signal transduction within the members of a bacterial
      two-component system. The proposed model takes into account post-translational
      modifications in terms of elementary phosphotransfer kinetics. Sources of
      fluctuations due to autophosphorylation, kinase, and phosphatase activity of the
      sensor kinase have been considered in the model via Langevin equations, which are
      then solved within the framework of linear noise approximation. The resultant
      analytical expression of phosphorylated response regulators are then used to
      quantify the noise profile of biologically motivated single and branched
      pathways. Enhancement and reduction of noise in terms of extra phosphate outflux
      and influx, respectively, have been analyzed for the branched system.
      Furthermore, the role of fluctuations of the network output in the regulation of
      a promoter with random activation-deactivation dynamics has been analyzed. 

PMID- 24125304
TI  - Microtubule catastrophe from protofilament dynamics.
AB  - The disappearance of the guanosine triphosphate- (GTP) tubulin cap is widely
      believed to be the forerunner event for the growth-shrinkage transition
      ("catastrophe") in microtubule filaments in eukaryotic cells. We study a discrete
      version of a stochastic model of the GTP cap dynamics, originally proposed by
      Flyvbjerg, Holy, and Leibler [Phys. Rev. Lett. 73, 2372 (1994)]. Our model
      includes both spontaneous and vectorial hydrolysis, as well as dissociation of a
      nonhydrolyzed dimer from the filament after incorporation. In the first part of
      the paper, we apply this model to a single protofilament of a microtubule. A
      catastrophe transition is defined for each protofilament, similarly to the
      earlier one-dimensional models, the frequency of occurrence of which is then
      calculated under various conditions but without explicit assumption of steady
      state conditions. Using a perturbative approach, we show that the leading
      asymptotic behavior of the protofilament catastrophe in the limit of large growth
      velocities is remarkably similar across different models. In the second part of
      the paper, we extend our analysis to the entire filament by making a conjecture
      that a minimum number of such transitions are required to occur for the onset of
      microtubule catastrophe. The frequency of microtubule catastrophe is then
      determined using numerical simulations and compared with analytical and
      semianalytical estimates made under steady-state and quasi-steady-state
      assumptions, respectively, for the protofilament dynamics. A few relevant
      experimental results are analyzed in detail and compared with predictions from
      the model. Our results indicate that loss of GTP cap in two to three
      protofilaments is necessary to trigger catastrophe in a microtubule. 

PMID- 24125305
TI  - Minimal model for stem-cell differentiation.
AB  - To explain the differentiation of stem cells in terms of dynamical systems
      theory, models of interacting cells with intracellular protein expression
      dynamics are analyzed and simulated. Simulations were carried out for all
      possible protein expression networks consisting of two genes under cell-cell
      interactions mediated by the diffusion of a protein. Networks that show cell
      differentiation are extracted and two forms of symmetric differentiation based on
      Turing's mechanism and asymmetric differentiation are identified. In the latter
      network, the intracellular protein levels show oscillatory dynamics at a single
      cell level, while cell-to-cell synchronicity of the oscillation is lost with an
      increase in the number of cells. Differentiation to a fixed-point-type behavior
      follows with a further increase in the number of cells. The cell type with
      oscillatory dynamics corresponds to a stem cell that can both proliferate and
      differentiate, while the latter fixed-point type only proliferates. This
      differentiation is analyzed as a saddle-node bifurcation on an invariant circle,
      while the number ratio of each cell type is shown to be robust against
      perturbations due to self-consistent determination of the effective bifurcation
      parameter as a result of the cell-cell interaction. Complex cell differentiation
      is designed by combing these simple two-gene networks. The generality of the
      present differentiation mechanism, as well as its biological relevance, is
      discussed.

PMID- 24125306
TI  - Symmetry breaking in optimal timing of traffic signals on an idealized two-way
      street.
AB  - Simple physical models based on fluid mechanics have long been used to understand
      the flow of vehicular traffic on freeways; analytically tractable models of flow
      on an urban grid, however, have not been as extensively explored. In an ideal
      world, traffic signals would be timed such that consecutive lights turned green
      just as vehicles arrived, eliminating the need to stop at each block.
      Unfortunately, this "green-wave" scenario is generally unworkable due to
      frustration imposed by competing demands of traffic moving in different
      directions. Until now this has typically been resolved by numerical simulation
      and optimization. Here, we develop a theory for the flow in an idealized system
      consisting of a long two-way road with periodic intersections. We show that
      optimal signal timing can be understood analytically and that there are
      counterintuitive asymmetric solutions to this signal coordination problem. We
      further explore how these theoretical solutions degrade as traffic conditions
      vary and automotive density increases.

PMID- 24125307
TI  - Time evolution of damage due to environmentally assisted aging in a fiber bundle
      model.
AB  - Damage growth in composite materials is a complex process which is of interest in
      many fields of science and engineering. We consider this problem in a fiber
      bundle model where fibers undergo an aging process due to the accumulation of
      damage driven by the locally acting stress in a chemically active environment. By
      subjecting the bundle to a constant external load, fibers fail either when the
      load on them exceeds their individual intrinsic strength or when the accumulated
      internal damage exceeds a random threshold. We analyze the time evolution of the
      breaking process under low external loads where aging of fibers dominates. In the
      mean field limit, we show analytically that the aging system continuously
      accelerates in a way which can be characterized by an inverse power law of the
      event rate with a singularity that defines a failure time. The exponent is not
      universal; it depends on the details of the aging process. For localized load
      sharing, a more complex damage process emerges which is dominated by distinct
      spatial regions of the system with different degrees of stress concentration.
      Analytical calculations revealed that the final acceleration to global failure is
      preceded by a stationary accumulation of damage. When the disorder is strong, the
      accelerating phase has the same functional behavior as in the mean field limit.
      The analytical results are verified by computer simulations. 

PMID- 24125308
TI  - Evolutionary vaccination dilemma in complex networks.
AB  - In this work we analyze the evolution of voluntary vaccination in networked
      populations by entangling the spreading dynamics of an influenza-like disease
      with an evolutionary framework taking place at the end of each influenza season
      so that individuals take or do not take the vaccine upon their previous
      experience. Our framework thus puts in competition two well-known dynamical
      properties of scale-free networks: the fast propagation of diseases and the
      promotion of cooperative behaviors. Our results show that when vaccine is
      perfect, scale-free networks enhance the vaccination behavior with respect to
      random graphs with homogeneous connectivity patterns. However, when imperfection
      appears we find a crossover effect so that the number of infected (vaccinated)
      individuals increases (decreases) with respect to homogeneous networks, thus
      showing the competition between the aforementioned properties of scale-free
      graphs.

PMID- 24125309
TI  - Solitons and kinks in a general car-following model.
AB  - We study a general car-following model of traffic flow on an infinitely long
      single-lane road, which assumes that a car's acceleration depends on time-delayed
      values of its own speed, the headway between it and the car ahead, and the rate
      of change of headway, but makes minimal assumptions about the functional form of
      that dependence. We present a detailed characterization of the onset of linear
      instability; in particular we find a specific limit on the delay time below which
      the marginal wave number at the onset of instability is zero, and another
      specific limit on the delay time above which steady flow is always unstable.
      Crucially, the threshold of absolute stability generally does not coincide with
      an inflection point of the steady-state velocity function. When the marginal
      perturbation at onset has wave number 0, we show that Burgers and Korteweg-de
      Vries (KdV) equations can be derived under the usual assumptions, and that
      corrections to the KdV equation "select" a single member of the one-parameter set
      of its one-soliton solutions by driving a slow evolution of the soliton
      parameter. While in previous models this selected soliton has always marked the
      threshold of a finite-amplitude instability of linearly stable steady flow, we
      find that it can alternatively be a stable, small-amplitude jam that occurs when
      steady flow is linearly unstable. The model reduces to the usual modified
      Korteweg-de Vries (mKdV) equation only in the special situation that the
      threshold of absolute stability coincides with an inflection point of the steady
      state velocity function; in general, near the threshold of absolute stability the
      model reduces instead to a KdV equation in the regime of small solitons, while
      near an inflection point it reduces to a Hayakawa-Nakanishi equation. Like the
      mKdV equation, the Hayakawa-Nakanishi equation admits a continuous family of kink
      solutions, and the selection criterion arising from the corrections to this
      equation can be written down explicitly.

PMID- 24125310
TI  - Quantitative modeling of degree-degree correlation in complex networks.
AB  - This paper presents an approach to the modeling of degree-degree correlation in
      complex networks. Thus, a simple function, Delta(k', k), describing specific
      degree-to-degree correlations is considered. The function is well suited to
      graphically depict assortative and disassortative variations within networks. To
      quantify degree correlation variations, the joint probability distribution
      between nodes with arbitrary degrees, P(k', k), is used. Introduction of the end
      degree probability function as a basic variable allows using group theory to
      derive mathematical models for P(k', k). In this form, an expression,
      representing a family of seven models, is constructed with the needed
      normalization conditions. Applied to Delta(k', k), this expression predicts a
      nonuniform distribution of degree correlation in networks, organized in two
      assortative and two disassortative zones. This structure is actually observed in
      a set of four modeled, technological, social, and biological networks. A
      regression study performed on 15 actual networks shows that the model describes
      quantitatively degree-degree correlation variations.

PMID- 24125311
TI  - Characterizing graph symmetries through quantum Jensen-Shannon divergence.
AB  - In this paper we investigate the connection between quantum walks and graph
      symmetries. We begin by designing an experiment that allows us to analyze the
      behavior of the quantum walks on the graph without causing the wave function
      collapse. To achieve this, we base our analysis on the recently introduced
      quantum Jensen-Shannon divergence. In particular, we show that the quantum Jensen
      Shannon divergence between the evolution of two quantum walks with suitably
      defined initial states is maximum when the graph presents symmetries. Hence, we
      assign to each pair of nodes of the graph a value of the divergence, and we
      average over all pairs of nodes to characterize the degree of symmetry possessed
      by a graph. 

PMID- 24125312
TI  - Spectral properties of the Laplacian of multiplex networks.
AB  - One of the more challenging tasks in the understanding of dynamical properties of
      models on top of complex networks is to capture the precise role of multiplex
      topologies. In a recent paper, Gomez et al. [Phys. Rev. Lett. 110, 028701
      (2013)], some of the authors proposed a framework for the study of diffusion
      processes in such networks. Here, we extend the previous framework to deal with
      general configurations in several layers of networks and analyze the behavior of
      the spectrum of the Laplacian of the full multiplex. We derive an interesting
      decoupling of the problem that allow us to unravel the role played by the
      interconnections of the multiplex in the dynamical processes on top of them.
      Capitalizing on this decoupling we perform an asymptotic analysis that allow us
      to derive analytical expressions for the full spectrum of eigenvalues. This
      spectrum is used to gain insight into physical phenomena on top of multiplex,
      specifically, diffusion processes and synchronizability.

PMID- 24125313
TI  - Link-based formalism for time evolution of adaptive networks.
AB  - Network topology and nodal dynamics are two fundamental stones of adaptive
      networks. Detailed and accurate knowledge of these two ingredients is crucial for
      understanding the evolution and mechanism of adaptive networks. In this paper, by
      adopting the framework of the adaptive SIS model proposed by Gross et al. [Phys.
      Rev. Lett. 96, 208701 (2006)] and carefully utilizing the information of degree
      correlation of the network, we propose a link-based formalism for describing the
      system dynamics with high accuracy and subtle details. Several specific degree
      correlation measures are introduced to reveal the coevolution of network topology
      and system dynamics. 

PMID- 24125314
TI  - Fokker-Planck description for the queue dynamics of large tick stocks.
AB  - Motivated by empirical data, we develop a statistical description of the queue
      dynamics for large tick assets based on a two-dimensional Fokker-Planck
      (diffusion) equation. Our description explicitly includes state dependence, i.e.,
      the fact that the drift and diffusion depend on the volume present on both sides
      of the spread. "Jump" events, corresponding to sudden changes of the best limit
      price, must also be included as birth-death terms in the Fokker-Planck equation.
      All quantities involved in the equation can be calibrated using high-frequency
      data on the best quotes. One of our central findings is that the dynamical
      process is approximately scale invariant, i.e., the only relevant variable is the
      ratio of the current volume in the queue to its average value. While the latter
      shows intraday seasonalities and strong variability across stocks and time
      periods, the dynamics of the rescaled volumes is universal. In terms of rescaled
      volumes, we found that the drift has a complex two-dimensional structure, which
      is a sum of a gradient contribution and a rotational contribution, both stable
      across stocks and time. This drift term is entirely responsible for the dynamical
      correlations between the ask queue and the bid queue. 

PMID- 24125315
TI  - Exponential random graph models for networks with community structure.
AB  - Although the community structure organization is an important characteristic of
      real-world networks, most of the traditional network models fail to reproduce the
      feature. Therefore, the models are useless as benchmark graphs for testing
      community detection algorithms. They are also inadequate to predict various
      properties of real networks. With this paper we intend to fill the gap. We
      develop an exponential random graph approach to networks with community
      structure. To this end we mainly built upon the idea of blockmodels. We consider
      both the classical blockmodel and its degree-corrected counterpart and study many
      of their properties analytically. We show that in the degree-corrected
      blockmodel, node degrees display an interesting scaling property, which is
      reminiscent of what is observed in real-world fractal networks. A short
      description of Monte Carlo simulations of the models is also given in the hope of
      being useful to others working in the field.

PMID- 24125316
TI  - Universal properties of magnetization dynamics in polycrystalline ferromagnetic
      films.
AB  - We investigate the scaling behavior in the statistical properties of Barkhausen
      noise in ferromagnetic films. We apply the statistical treatment usually employed
      for bulk materials in experimental Barkhausen noise time series measured with the
      traditional inductive technique in polycrystalline ferromagnetic films having
      different thickness from 100 to 1000 nm and determine the scaling exponents.
      Based on this procedure, we group the samples in a single universality class,
      since the scaling behavior of Barkhausen avalanches is characterized by exponents
      tau~1.5, alpha~2.0, and 1/sigmanuz~theta~2.0 for all the films. We interpret
      these results in terms of theoretical models and provide experimental evidence
      that a well-known mean-field model for the dynamics of a ferromagnetic domain
      wall in three-dimensional ferromagnets can be extended for films. We identify
      that the films present an universal three-dimensional magnetization dynamics,
      governed by long-range dipolar interactions, even at the smallest thicknesses,
      indicating that the two-dimensional magnetic behavior commonly verified for films
      cannot be generalized for all thickness ranges.

PMID- 24125317
TI  - Robust synchronization of spin-torque oscillators with an LCR load.
AB  - We study dynamics of a serial array of spin-torque oscillators with a parallel
      inductor-capacitor-resistor (LCR) load. In a large range of parameters the fully
      synchronous regime, where all the oscillators have the same state and the output
      field is maximal, is shown to be stable. However, not always such a robust
      complete synchronization develops from a random initial state; in many cases
      nontrivial clustering is observed, with a partial synchronization resulting in a
      quasiperiodic or chaotic mean-field dynamics. 

PMID- 24125318
TI  - Modeling two-dimensional magnetic resonance measurements in coupled pore systems.
AB  - We present numerical simulations of a two-dimensional (2D) nuclear magnetic
      resonance process, T_{2}-storage-T_{2}, on a simple mixed porosity system, the
      micrograin consolidation (MUGC) model. The results of these calculations are
      compared with predictions based on the analytic two-site exchange model, for
      which we have independently established numerical values for all the input
      parameters. Although there is qualitative and semiquantitative agreement between
      the two models, we identify specific instances where the two-site model fails to
      properly describe the combined effects of relaxation and diffusion. Generally,
      these instances occur when a gradient in magnetization within the large pores of
      the MUGC model is established during the initial phase of the 2D process. The two
      site model assumes that the magnetization is spatially uniform within each of its
      subpore systems and thus cannot describe such effects.

PMID- 24125319
TI  - Symmetry breaking in binary chains with nonlinear sites.
AB  - We consider a system of two or four nonlinear sites coupled with binary chain
      waveguides. When a monochromatic wave is injected into the first (symmetric)
      propagation channel, the presence of cubic nonlinearity can lead to symmetry
      breaking, giving rise to emission of antisymmetric wave into the second
      (antisymmetric) propagation channel of the waveguides. We found that in the case
      of nonlinear plaquette, there is a domain in the parameter space where neither
      symmetry-preserving nor symmetry-breaking stable stationary solutions exit. As a
      result, injection of a monochromatic symmetric wave gives rise to emission of
      nonsymmetric satellite waves with energies differing from the energy of the
      incident wave. Thus, the response exhibits nonmonochromatic behavior.

PMID- 24125320
TI  - Chimeras with multiple coherent regions.
AB  - We study chimeric states in a coupled phase oscillator system with piecewise
      linear nonlocal coupling. By modifying the details of the coupling, it is
      possible to obtain multiple chimeric states with a specified number of coherent
      regions and with specified phase relationships. The case of a two-component
      chimera is illustrated and the generalization to arbitrary chimeric
      configurations is discussed. The phase relations between the two clusters of
      phase oscillators is described in some detail.

PMID- 24125321
TI  - Rotation of the trajectories of bright solitons and realignment of intensity
      distribution in the coupled nonlinear Schrodinger equation.
AB  - We reconsider the collisional dynamics of bright solitons in the coupled
      nonlinear Schrodinger equation. We observe that apart from the intensity
      redistribution in the interaction of bright solitons, one also witnesses a
      rotation of the trajectories of bright solitons. The angle of rotation can be
      varied by suitably manipulating the self-phase-modulation (SPM) or cross-phase
      modulation (XPM) parameters. The rotation of the trajectories of the bright
      solitons arises due to the excess energy that is injected into the dynamical
      system through SPM or XPM. This extra energy contributes not only to the rotation
      of the trajectories, but also to the realignment of intensity distribution
      between the two modes. We also notice that the angular separation between the
      bright solitons can also be maneuvered suitably. The above results, which exclude
      quantum superposition for the field vectors, may have wider ramifications in
      nonlinear optics, Bose-Einstein condensates, and left- and right-handed
      metamaterials.

PMID- 24125322
TI  - Enhanced control of saddle steady states of dynamical systems.
AB  - An adaptive feedback technique for stabilizing a priori unknown saddle steady
      states of dynamical systems is described. The method is based on an unstable low
      pass filter combined with a stable low-pass filter. The cutoff frequencies of
      both filters can be set relatively high. This allows considerable increase in the
      rate of convergence to the steady state. We demonstrate numerically and
      experimentally that the technique is robust to the influence of unknown external
      forces, which change the position of the steady state in the phase space.
      Experiments have been performed using electrical circuits imitating the damped
      Duffing-Holmes and chaotic Lindberg systems.

PMID- 24125323
TI  - Discrete localized modes supported by an inhomogeneous defocusing nonlinearity.
AB  - We report that infinite and semi-infinite lattices with spatially inhomogeneous
      self-defocusing (SDF) onsite nonlinearity, whose strength increases rapidly
      enough toward the lattice periphery, support stable unstaggered (UnST) discrete
      bright solitons, which do not exist in lattices with the spatially uniform SDF
      nonlinearity. The UnST solitons coexist with stable staggered (ST) localized
      modes, which are always possible under the defocusing onsite nonlinearity. The
      results are obtained in a numerical form and also by means of variational
      approximation (VA). In the semi-infinite (truncated) system, some solutions for
      the UnST surface solitons are produced in an exact form. On the contrary to
      surface discrete solitons in uniform truncated lattices, the threshold value of
      the norm vanishes for the UnST solitons in the present system. Stability regions
      for the novel UnST solitons are identified. The same results imply the existence
      of ST discrete solitons in lattices with the spatially growing self-focusing
      nonlinearity, where such solitons cannot exist either if the nonlinearity is
      homogeneous. In addition, a lattice with the uniform onsite SDF nonlinearity and
      exponentially decaying intersite coupling is introduced and briefly considered.
      Via a similar mechanism, it may also support UnST discrete solitons. The results
      may be realized in arrayed optical waveguides and collisionally inhomogeneous
      Bose-Einstein condensates trapped in deep optical lattices. A generalization for
      a two-dimensional system is briefly considered.

PMID- 24125324
TI  - Measure synchronization in a two-species bosonic Josephson junction.
AB  - Measure synchronization (MS) in a two-species bosonic Josephson junction (BJJ) is
      studied based on semiclassical theory. Six different scenarios for MS, including
      two in the Josephson oscillation regime (the zero-phase mode) and four in the
      self-trapping regime (the pi-phase mode), are clearly shown. Systematic
      investigations of the common features behind these different scenarios are
      performed. We show that the average energies of the two species merge at the MS
      transition point. The scaling of the power law near the MS transition is verified
      and the critical exponent is 1/2 for all of the different scenarios for MS. We
      also illustrate MS in a three-dimensional phase space; from this illustration,
      more detailed information on the dynamical process can be obtained. In
      particular, by analyzing the Poincare sections with changing interspecies
      interactions, we find that the two-species BJJ exhibits separatrix crossing
      behavior at the MS transition point and such behavior depicts the general
      mechanism behind the different scenarios for the MS transitions. The new critical
      behavior found in a two-species BJJ is expected to be found in real systems of
      atomic Bose gases.

PMID- 24125325
TI  - Nonlinear dynamics of an injected quantum cascade laser.
AB  - The stability properties of an injected quantum cascade laser are investigated
      analytically on the basis of current estimates of the laser parameters. We show
      that in addition to stable locking, Hopf bifurcations leading to pulsating
      intensities are possible. We discuss the stability diagrams in terms of the
      detuning and the injection rate for different values of the linewidth enhancement
      factor. The analysis indicates domains of coexistence between two stable steady
      states (bistability) or between a stable steady state and stable periodic
      oscillations. All predictions are verified numerically by determining bifurcation
      diagrams from the laser rate equations.

PMID- 24125326
TI  - Hopf bifurcation and multistability in a system of phase oscillators.
AB  - We study the phase reduction of two coupled van der Pol oscillators with
      asymmetric repulsive coupling under an external harmonic force. We show that the
      system of two phase oscillators undergoes a Hopf bifurcation and possesses
      multistability on a 2pi-periodic phase plane. We describe the bifurcation
      mechanisms of formation of multistability in the phase-reduced system and show
      that the Andronov-Hopf bifurcation in the phase-reduced system is not an artifact
      of the reduction approach but, indeed, has its prototype in the nonreduced
      system. The bifurcational mechanisms presented in the paper enable one to
      describe synchronization effects in a wide class of interacting systems with
      repulsive coupling e.g., genetic oscillators.

PMID- 24125327
TI  - Efficient recovery of dynamic behavior in coupled oscillator networks.
AB  - We study an effective method to recover dynamic activity in coupled oscillator
      networks that have been damaged and lost oscillatory dynamics owing to some
      inactivated or deteriorated oscillator elements. Recovery of the dynamic behavior
      can be achieved by newly connecting intact oscillators to the network. We
      analytically and numerically examine the proportion of the oscillators that are
      needed to be supported by intact oscillators for recovery of oscillation
      dynamics. Our results show that it can be more effective to preferentially
      support active oscillators in the damaged network than to preferentially support
      inactivated ones. The conditions for this counterintuitive result are discussed.
      Our framework could be a theoretical foundation for understanding regeneration of
      oscillatory dynamics in physical and biological systems.

PMID- 24125328
TI  - Multivariate recurrence network analysis for characterizing horizontal oil-water
      two-phase flow.
AB  - Characterizing complex patterns arising from horizontal oil-water two-phase flows
      is a contemporary and challenging problem of paramount importance. We design a
      new multisector conductance sensor and systematically carry out horizontal oil
      water two-phase flow experiments for measuring multivariate signals of different
      flow patterns. We then infer multivariate recurrence networks from these
      experimental data and investigate local cross-network properties for each
      constructed network. Our results demonstrate that a cross-clustering coefficient
      from a multivariate recurrence network is very sensitive to transitions among
      different flow patterns and recovers quantitative insights into the flow behavior
      underlying horizontal oil-water flows. These properties render multivariate
      recurrence networks particularly powerful for investigating a horizontal oil
      water two-phase flow system and its complex interacting components from a network
      perspective.

PMID- 24125329
TI  - Time-delay autosynchronization control of defect turbulence in the cubic-quintic
      complex Ginzburg-Landau equation.
AB  - We investigate the effectiveness of a Global time-delay autosynchronization
      control scheme aimed at stabilizing traveling wave solutions of the cubic-quintic
      Ginzburg-Landau equation in the Benjamin-Feir-Newell unstable regime. Numerical
      simulations show that a global control can be efficient and also can create other
      patterns such as spatiotemporal intermittency regimes, standing waves, or uniform
      oscillations.

PMID- 24125330
TI  - Delayed feedback control of unstable steady states with high-frequency modulation
      of the delay.
AB  - We analyze the stabilization of unstable steady states by delayed feedback
      control with a periodic time-varying delay in the regime of a high-frequency
      modulation of the delay. The average effect of the delayed feedback term in the
      control force is equivalent to a distributed delay in the interval of the
      modulation, and the obtained distribution depends on the type of the modulation.
      In our analysis we use a simple generic normal form of an unstable focus, and
      investigate the effects of phase-dependent coupling and the influence of the
      control loop latency on the controllability. In addition, we have explored the
      influence of the modulation of the delays in multiple delay feedback schemes
      consisting of two independent delay lines of Pyragas type. A main advantage of
      the variable delay is the considerably larger domain of stabilization in
      parameter space.

PMID- 24125331
TI  - Time fluctuations in isolated quantum systems of interacting particles.
AB  - Numerically, we study the time fluctuations of few-body observables after
      relaxation in isolated dynamical quantum systems of interacting particles. Our
      results suggest that they decay exponentially with system size in both regimes,
      integrable and chaotic. The integrable systems considered are solvable with the
      Bethe ansatz and have a highly nondegenerate spectrum. This is in contrast with
      integrable Hamiltonians mappable to noninteracting ones. We show that the
      coefficient of the exponential decay depends on the level of delocalization of
      the initial state with respect to the energy shell.

PMID- 24125332
TI  - Weakly noisy chaotic scattering.
AB  - The effect of a weak source of noise on the chaotic scattering is relevant to
      situations of physical interest. We investigate how a weak source of additive
      uncorrelated Gaussian noise affects both the dynamics and the topology of a
      paradigmatic chaotic scattering problem as the one taking place in the open
      nonhyperbolic regime of the Henon-Heiles Hamiltonian system. We have found long
      transients for the time escape distributions for critical values of the noise
      intensity for which the particles escape slower as compared with the noiseless
      case. An analysis of the survival probability of the scattering function versus
      the Gaussian noise intensity shows a smooth curve with one local maximum and with
      one local minimum which are related to those long transients and with the basin
      structure in phase space. On the other hand, the computation of the exit basins
      in phase space shows a quadratic curve for which the basin boundaries lose their
      fractal-like structure as noise turned on.

PMID- 24125333
TI  - Three-body interactions with time delay.
AB  - This work focuses on the dynamics of globally coupled phase oscillators with
      three-body interaction and time delay. Analytic estimates regarding the stability
      of the incoherent solution are presented. Expressions for the phase
      synchronization frequencies and their stability are also derived. These
      theoretical results are supplemented with appropriate numerical computations.
      Numerical results regarding the fluctuations observed in the synchronization
      order parameter are then discussed. Some comparative results for phase
      synchronization in two-body, three-body, and mixed-coupled systems for different
      coupling combinations are also presented. 

PMID- 24125334
TI  - Amplitude death in nonlinear oscillators with mixed time-delayed coupling.
AB  - Amplitude death (AD) is an emergent phenomenon whereby two or more autonomously
      oscillating systems completely lose their oscillations due to coupling. In this
      work, we study AD in nonlinear oscillators with mixed time-delayed coupling,
      which is a combination of instantaneous and time-delayed couplings. We find that
      the mixed time-delayed coupling favors the onset of AD for a larger set of
      parameters than in the limiting cases of purely instantaneous or completely time
      delayed coupling. Coupled identical oscillators experience AD under instantaneous
      coupling mixed with a small proportion of time-delayed coupling. Our work gives a
      deeper understanding of delay-induced AD in coupled nonlinear oscillators. 

PMID- 24125335
TI  - Competing resonances in spatially forced pattern-forming systems.
AB  - Spatial periodic forcing can entrain a pattern-forming system in the same way as
      temporal periodic forcing can entrain an oscillator. The forcing can lock the
      pattern's wave number to a fraction of the forcing wave number within tonguelike
      domains in the forcing parameter plane, it can increase the pattern's amplitude,
      and it can also create patterns below their onset. We derive these results using
      a multiple-scale analysis of a spatially forced Swift-Hohenberg equation in one
      spatial dimension. In two spatial dimensions the one-dimensional forcing can
      induce a symmetry-breaking instability that leads to two-dimensional (2D)
      patterns, rectangular or oblique. These patterns resonate with the forcing by
      locking their wave-vector component in the forcing direction to half the forcing
      wave number. The range of this type of 2:1 resonance overlaps with the 1:1
      resonance tongue of stripe patterns. Using a multiple-scale analysis in the
      overlap region we show that the 2D patterns can destabilize the 1:1 resonant
      stripes even at exact resonance. This result sheds new light on the use of
      spatial periodic forcing for controlling patterns.

PMID- 24125336
TI  - Analysis of a solvable model of a phase oscillator network on a circle with
      infinite-range Mexican-hat-type interaction.
AB  - We study a phase oscillator network on a circle with an infinite-range
      interaction. First, we treat the Mexican-hat interaction with the zeroth and
      first Fourier components. We give detailed derivations of the auxiliary equations
      for the phases and self-consistent equations for the amplitudes. We solve these
      equations and characterize the nontrivial solutions in terms of order parameters
      and the rotation number. Furthermore, we derive the boundaries of the bistable
      regions and study the bifurcation structures in detail. Expressions for location
      dependent resultant frequencies and entrained phases are also derived. Secondly,
      we treat a different interaction that is composed of mth and nth Fourier
      components, where m<n, and we study its nontrivial solutions. In both cases, the
      results of numerical simulations agree quite well with the theoretical results.

PMID- 24125337
TI  - Deformation of a Peregrine soliton by fluctuating backgrounds.
AB  - A generalized Peregrine soliton moving on a fluctuating background is
      constructed. The agreement with the experimental results is improved compared to
      the standard Peregrine soliton. It has a deformed shape asymmetric with respect
      to time, and the peak values are not always 3. 

PMID- 24125338
TI  - Electrokinetics over charge-modulated surfaces in the presence of patterned
      wettability: role of the anisotropic streaming potential.
AB  - In the present study, we focus on evaluating the induced streaming electric field
      along the orthogonal directions in a narrow fluidic confinement in the presence
      of patterned surface wettability and modulated surface charges. We attempt to
      assess the implications of such modulations on the related important quantities
      and pinpoint the regimes of improved induced streaming potential field and the
      resulting anisotropy in the induced potential. Our results reveal that for
      certain combinations of the parameters characterizing the modulated slip, a
      significant amount of augmentation in the streaming electric field might be
      obtained, whereas in other cases the effects may lead to adverse consequences. We
      further demonstrate that the presence of anisotropic modulations on the channel
      walls give rise to considerable off-diagonal effects, which makes the streaming
      potential "disoriented" with the applied pressure gradient, when the same is not
      applied along one of the orthogonal directions. Our analysis also shows that one
      can remove such "mis-orientations" by finely tuning several relevant flow and
      geometric parameters, which may bear immense scientific and technological
      consequences towards an improved design of miniaturized energy conversion
      devices. 

PMID- 24125339
TI  - Pore-scale micro-computed-tomography imaging: nonwetting-phase cluster-size
      distribution during drainage and imbibition.
AB  - We investigated the cluster-size distribution of the residual nonwetting phase in
      a sintered glass-bead porous medium at two-phase flow conditions, by means of
      micro-computed-tomography (MUCT) imaging with pore-scale resolution. Cluster-size
      distribution functions and cluster volumes were obtained by image analysis for a
      range of injected pore volumes under both imbibition and drainage conditions; the
      field of view was larger than the porosity-based representative elementary volume
      (REV). We did not attempt to make a definition for a two-phase REV but used the
      nonwetting-phase cluster-size distribution as an indicator. Most of the
      nonwetting-phase total volume was found to be contained in clusters that were one
      to two orders of magnitude larger than the porosity-based REV. The largest
      observed clusters in fact ranged in volume from 65% to 99% of the entire
      nonwetting phase in the field of view. As a consequence, the largest clusters
      observed were statistically not represented and were found to be smaller than the
      estimated maximum cluster length. The results indicate that the two-phase REV is
      larger than the field of view attainable by MUCT scanning, at a resolution which
      allows for the accurate determination of cluster connectivity. 

PMID- 24125340
TI  - Time persistence of floating-particle clusters in free-surface turbulence.
AB  - We study the dispersion of light particles floating on a flat shear-free surface
      of an open channel in which the flow is turbulent. This configuration mimics the
      motion of buoyant matter (e.g., phytoplankton, pollutants, or nutrients) in water
      bodies when surface waves and ripples are smooth or absent. We perform direct
      numerical simulation of turbulence coupled with Lagrangian particle tracking,
      considering different values of the shear Reynolds number (Re_{tau}=171 and 509)
      and of the Stokes number (0.06<St<1 in viscous units). Results show that particle
      buoyancy induces clusters that evolve towards a long-term fractal distribution in
      a time much longer than the Lagrangian integral fluid time scale, indicating that
      such clusters overlive the surface turbulent structures which produced them. We
      quantify cluster dynamics, crucial when modeling dispersion in free-surface flow
      turbulence, via the time evolution of the cluster correlation dimension.

PMID- 24125341
TI  - Bacterial turbulence reduction by passive magnetic particle chains.
AB  - We report the experimental observation of the bacterial turbulence reduction in
      dense E. coli suspensions by increasing the coupling of passive particle
      additives (paramagnetic particles). Applying an external magnetic field induces
      magnetic dipoles for particles and causes the formation of vertical chain
      bundles, which are hard for bacterial flows to tilt and break. The larger
      effective drag coefficient of chains causes slow horizontal motion of chains,
      which in turn form obstacles to suppress bacterial flows through the strong
      correlation in coherent bacterial clusters and intercluster interaction. The
      interruption of the upward energy flow from individual self-propelling bacteria
      to the larger scale in the bacterial turbulence with multiscaled coherent flow by
      the chain bundle leads to more severe suppression in the low frequency (wave
      number) regimes of the power spectra.

PMID- 24125342
TI  - Scaling of turbulent flame speed for expanding flames with Markstein diffusion
      considerations.
AB  - In this paper we clarify the role of Markstein diffusivity, which is the product
      of the planar laminar flame speed and the Markstein length, on the turbulent
      flame speed and its scaling, based on experimental measurements on constant
      pressure expanding turbulent flames. Turbulent flame propagation data are
      presented for premixed flames of mixtures of hydrogen, methane, ethylene, n
      butane, and dimethyl ether with air, in near-isotropic turbulence in a dual
      chamber, fan-stirred vessel. For each individual fuel-air mixture presented in
      this work and the recently published iso-octane data from Leeds, normalized
      turbulent flame speed data of individual fuel-air mixtures approximately follow a
      Re_{T,f}^{0.5} scaling, for which the average radius is the length scale and
      thermal diffusivity is the transport property of the turbulence Reynolds number.
      At a given Re_{T,f}^{}, it is experimentally observed that the normalized
      turbulent flame speed decreases with increasing Markstein number, which could be
      explained by considering Markstein diffusivity as the leading dissipation
      mechanism for the large wave number flame surface fluctuations. Consequently, by
      replacing thermal diffusivity with the Markstein diffusivity in the turbulence
      Reynolds number definition above, it is found that normalized turbulent flame
      speeds could be scaled by Re_{T,M}^{0.5} irrespective of the fuel, equivalence
      ratio, pressure, and turbulence intensity for positive Markstein number flames.

PMID- 24125343
TI  - Orbital trajectory of an acoustic bubble in a cylindrical resonator.
AB  - Acoustic cavitation-induced microbubbles in a cylindrical resonator filled with
      water tend to concentrate into ring patterns due to the cylindrical geometry of
      the system. The shape of these ring patterns is directly linked to the Bjerknes
      force distribution in the resonator. Experimental observations showed that
      cavitation bubbles located in the vicinity of this ring may exhibit a spiraling
      behavior around the pressure nodal line. This spiraling phenomenon is numerically
      studied, the conditions for which a single cavitation bubble follows an orbital
      trajectory are established, and the influences of the acoustic pressure amplitude
      and the initial bubble radius are investigated. 

PMID- 24125344
TI  - Minimal model for zero-inertia instabilities in shear-dominated non-Newtonian
      flows.
AB  - The emergence of fluid instabilities in the relevant limit of vanishing fluid
      inertia (i.e., arbitrarily close to zero Reynolds number) has been investigated
      for the well-known Kolmogorov flow. The finite-time shear-induced order-disorder
      transition of the non-Newtonian microstructure and the corresponding viscosity
      change from lower to higher values are the crucial ingredients for the
      instabilities to emerge. The finite-time low-to-high viscosity change for
      increasing shear characterizes the rheopectic fluids. The instability does not
      emerge in shear-thinning or -thickening fluids where viscosity adjustment to
      local shear occurs instantaneously. The lack of instabilities arbitrarily close
      to zero Reynolds number is also observed for thixotropic fluids, in spite of the
      fact that the viscosity adjustment time to shear is finite as in rheopectic
      fluids. Renormalized perturbative expansions (multiple-scale expansions), energy
      based arguments (on the linearized equations of motion), and numerical results
      (of suitable eigenvalue problems from the linear stability analysis) are the main
      tools leading to our conclusions. Our findings may have important consequences in
      all situations where purely hydrodynamic fluid instabilities or mixing are
      inhibited due to negligible inertia, as in microfluidic applications. To trigger
      mixing in these situations, suitable (not necessarily viscoelastic) non-Newtonian
      fluid solutions appear as a valid answer. Our results open interesting questions
      and challenges in the field of smart (fluid) materials.

PMID- 24125345
TI  - Control of centrifugal fingering via a variable interfacial tension approach.
AB  - We study the centrifugal fingering instabilities that occur in rotating Hele-Shaw
      cells containing two different fluids. A weakly nonlinear analysis of the problem
      is performed, considering that the surface tension between the rotating fluids
      changes with the local curvature of the interface. It is shown that the coupling
      between the contact angle and the variable interfacial tension permits the
      control of the interface disturbances. As a result, linear perturbations and
      nonlinear finger competition phenomena can be properly controlled and suppressed.

PMID- 24125346
TI  - Thermal effects on the diffusive layer convection instability of an exothermic
      acid-base reaction front.
AB  - A buoyancy-driven hydrodynamic instability appearing when an aqueous acid
      solution of HCl overlies a denser alkaline aqueous solution of NaOH in a
      vertically oriented Hele-Shaw cell is studied both experimentally and
      theoretically. The peculiarity of this reactive convection pattern is its
      asymmetry with regard to the initial contact line between the two solutions as
      convective plumes develop in the acidic solution only. We investigate here by a
      linear stability analysis (LSA) of a reaction-diffusion-convection model of a
      simple A+B->C reaction the relative role of solutal versus thermal effects in the
      origin and location of this instability. We show that heat effects are much
      weaker than concentration-related ones such that the heat of reaction only plays
      a minor role on the dynamics. Computation of density profiles and of the
      stability analysis eigenfunctions confirm that the convective motions result from
      a diffusive layer convection mechanism whereby a locally unstable density
      stratification develops in the upper acidic layer because of the difference in
      the diffusion coefficients of the chemical species. The growth rate and
      wavelength of the pattern are determined experimentally as a function of the
      Brinkman parameter of the problem and compare favorably with the theoretical
      predictions of both LSA and nonlinear simulations.

PMID- 24125347
TI  - Dynamic wetting at the nanoscale.
AB  - Although the capillary spreading of a drop on a dry substrate is well studied,
      understanding and describing the physical mechanisms that govern the dynamics
      remain challenging. Here we study the dynamics of spreading of partially wetting
      nanodroplets by combining molecular dynamics simulations and continuum phase
      field simulations. The phase field simulations account for all the relevant
      hydrodynamics, i.e., capillarity, inertia, and viscous stresses. By coordinated
      continuum and molecular dynamics simulations, the macroscopic model parameters
      are extracted. For a Lennard-Jones fluid spreading on a planar surface, the
      liquid slip at the solid substrate is found to be significant, in fact crucial
      for the motion of the contact line. Evaluation of the different contributions to
      the energy transfer shows that the liquid slip generates dissipation of the same
      order as the bulk viscous dissipation or the energy transfer to kinetic energy.
      We also study the dynamics of spreading on a substrate with a periodic
      nanostructure. Here it is found that a nanostructure with a length scale
      commensurate with molecular size completely inhibits the liquid slip. The dynamic
      spreading is thus about 30% slower on a nanostructured surface compared to one
      that is atomically smooth.

PMID- 24125348
TI  - Dynamical-systems analysis and unstable periodic orbits in reacting flows behind
      symmetric bluff bodies.
AB  - Dynamical systems analysis is performed for reacting flows stabilized behind four
      symmetric bluff bodies to determine the effects of shape on the nature of flame
      stability, acoustic coupling, and vortex shedding. The task requires separation
      of regular, repeatable aspects of the flow from experimental noise and highly
      irregular, nonrepeatable small-scale structures caused primarily by viscous
      mediated energy cascading. The experimental systems are invariant under a
      reflection, and symmetric vortex shedding is observed throughout the parameter
      range. As the equivalence ratio-and, hence, acoustic coupling-is reduced, a
      symmetry-breaking transition to von Karman vortices is initiated. Combining
      principal-components analysis with a symmetry-based filtering, we construct
      bifurcation diagrams for the onset and growth of von Karman vortices. We also
      compute Lyapunov exponents for each flame holder to help quantify the
      transitions. Furthermore, we outline changes in the phase-space orbits that
      accompany the onset of von Karman vortex shedding and compute unstable periodic
      orbits (UPOs) embedded in the complex flows prior to and following the
      bifurcation. For each flame holder, we find a single UPO in flows without von
      Karman vortices and a pair of UPOs in flows with von Karman vortices. These
      periodic orbits organize the dynamics of the flow and can be used to reduce or
      control flow irregularities. By subtracting them from the overall flow, we are
      able to deduce the nature of irregular facets of the flows.

PMID- 24125349
TI  - Electrohydrodynamics of a compound drop.
AB  - The behavior of a compound drop, comprising two concentric fluid spheres, in a
      uniform electric field is studied analytically. The governing electrohydrodynamic
      equations are solved for Newtonian and immiscible fluids in the framework of
      leaky-dielectric theory and in the limit of small electric field strength and
      fluid inertia. A detailed analysis of the electric and flow fields is presented
      and it is shown that there will be four possible flow patterns in and around the
      globule, in terms of the direction of the external flow (pole-to-equator vs
      equator-to-pole) and the number of vortices (single-vortex vs double vortices) in
      the shell, and that the senses of the net electric shear stresses at the surfaces
      of the inner and the outer drops and their relative importance are the key
      parameters in setting these patterns. A circulation map is constructed, which is
      used to infer about the likelihood of the flow patterns and transition from one
      pattern to another for representative fluid systems. For small distortion from
      the spherical shape, the deformations of the inner and the outer drops are found
      using normal stress balances at the corresponding surfaces. It is shown that
      there will be four possible modes for the deformation of the compound drop, which
      are determined by the net normal electric and hydrodynamic stresses at the
      pertinent surfaces. The dynamic responses of the inner and the outer drops for
      representative fluid systems are studied using a deformation map, which
      characterizes the possibilities of the deformation modes and transition from one
      mode to another as a function of the fluid properties. 

PMID- 24125350
TI  - Fluctuations of a passive scalar in a turbulent mixing layer.
AB  - The turbulent flow originating downstream of the Kelvin-Helmholtz instability in
      a mixing layer has great relevance in many applications, ranging from atmospheric
      physics to combustion in technical devices. The mixing of a substance by the
      turbulent velocity field is usually involved. In this paper, a detailed
      statistical analysis of fluctuations of a passive scalar in the fully developed
      region of a turbulent mixing layer from a direct numerical simulation is
      presented. Passive scalar spectra show inertial ranges characterized by scaling
      exponents -4/3 and -3/2 in the streamwise and spanwise directions, in agreement
      with a recent theoretical analysis of passive scalar scaling in shear flows
      [Celani et al., J. Fluid Mech. 523, 99 (2005)]. Scaling exponents of high-order
      structure functions in the streamwise direction show saturation of intermittency
      with an asymptotic exponent zeta_{infinity}=0.4 at large orders. Saturation of
      intermittency is confirmed by the self-similarity of the tails of the probability
      density functions of the scalar increments at different scales r with the scaling
      factor r^{-zeta_{infinity}} and by the analysis of the cumulative probability of
      large fluctuations. Conversely, intermittency saturation is not observed for the
      spanwise increments and the relative scaling exponents agree with recent results
      for homogeneous isotropic turbulence with mean scalar gradient. Probability
      density functions of the scalar increments in the three directions are compared
      to assess anisotropy.

PMID- 24125351
TI  - Effects of solvent-mediated nonelectrostatic ion-ion interactions on a streaming
      potential in microchannels and nanochannels.
AB  - Here, we capture the consequences of solvent-mediated nonelectrostatic ion-ion
      interactions, coupled with the considerations of finite-sized effects of the
      ionic species, on electrokinetic transport in narrow fluidic confinements. We
      consider pressure-driven flow in microchannels and nanochannels in the presence
      of electrical double layer effects and analyze the establishment of a streaming
      potential as mediated by a Yukawa-like pair potential that integrates the ion
      specificity with the governing nonelectrostatic interactions. We bring out the
      influences of these interactions on electroviscous effects manifested due to the
      establishment of the streaming potential. Our considerations provide a plausible
      explanation for the gross overestimation of electrokinetic energy conversion
      efficiencies as predicted by classical electrical double layer theories that
      ignore nonelectrostatic interactions between the ionic species.

PMID- 24125352
TI  - Interaction between a fracture network and a cubic cavity.
AB  - The intersection between a network of polygonal fractures and a cubic cavity is
      numerically studied. Several probabilities are defined and particular attention
      is paid to the probabilities of intersection or not of the percolating cluster
      with the cavity; they depend on the size of the domain, on the fracture density,
      and on the relative size of the fractures and of the cavity. These probabilities
      are extrapolated to infinite domains. Analytical approximations are proposed
      which are in good agreement with the numerical data for sufficiently large
      densities. Some extensions of practical and theoretical interests are given in
      the concluding remarks. 

PMID- 24125353
TI  - Instability of a rotating liquid ring.
AB  - It is shown numerically that a rotating inviscid liquid ring has a temporally
      oscillating state, where the radius of the ring varies periodically because of
      the competition between the centrifugal force and the centripetal force caused by
      the surface tension. Stability analysis reveals that an enlarging or shrinking
      ring is unstable to a varicose-type mode, which is affected by both the radial
      velocity and the radius ratio between the cross section and the ring.
      Furthermore, uniform rotation of a ring leads to a traveling unstable mode, whose
      frequency is determined by a simple sinuous mode, while the surface shape is
      modulated by the varicose mode and twisted by the rotation-induced Coriolis
      force. 

PMID- 24125354
TI  - Scaling and unified characterization of flow instabilities in layered
      heterogeneous porous media.
AB  - The physics of miscible flow displacements with unfavorable mobility ratios
      through horizontal layered heterogeneous media is investigated. The flow model is
      solved numerically, and the effects of various physical parameters such as the
      injection velocity, diffusion, viscosity, and the heterogeneity length scale and
      variance are examined. The flow instability is characterized qualitatively
      through concentration contours as well as quantitatively through the mixing zone
      length and the breakthrough time. This characterization allowed us to identify
      four distinct regimes that govern the flow displacement. Furthermore, a scaling
      of the model resulted in generalized curves of the mixing zone length for any
      flow scenario in which the first three regimes of diffusion, channeling, and
      lateral dispersion superpose into a single unifying curve and allowed us to
      clearly identify the onset of the fourth regime. A critical effective Peclet
      number w_{c} based on the layers' width is proposed to identify flows where
      heterogeneity effects are expected to be important and those where the flow can
      be safely treated as homogeneous. A similar scaling of the breakthrough time was
      obtained and allowed us to identify two optimal effective Peclet numbers w_{opt}
      that result in the longest and shortest breakthrough times for any flow
      displacement.

PMID- 24125355
TI  - Experimental study of oblique impact between dry spheres and liquid layers.
AB  - Liquid addition is common in industrial fluidization-based processes. A detailed
      understanding of collision mechanics of particles with liquid layers is helpful
      to optimize these processes. The normal impact with liquid has been studied
      extensively; however, the studies on oblique impact with liquid are scarce. In
      this work, experiments are conducted to trace Al_{2}O_{3} spheres obliquely
      impacting on a surface covered by liquid layers, in which the free-fall spheres
      are disturbed initially by a horizontal gas flow. The oblique impact exhibits
      different rebound behaviors from normal collision due to the occurrence of strong
      rotation. The normal and tangential restitution coefficients (e_{n} and e_{t})
      and liquid bridge rupture time (t_{rup}) are analyzed. With increase in liquid
      layer thickness and viscosity, e_{n} and e_{t} decline, and t_{rup} increases.
      With increase in tangential velocity, e_{t} decreases first and then increases,
      whereas e_{n} remains nearly unchanged, and t_{rup} decreases constantly. A
      modified Stokes number is proposed to further explore the relation between
      restitution coefficients and the impact parameters. Finally, an analysis of
      energy dissipation shows that the contact deformation and liquid phase are the
      two main sources of total energy dissipation. Unexpectedly, the dissipative
      energy caused by the liquid phase is independent of tangential velocity.

PMID- 24125356
TI  - Experimental investigation of the stability of the floating water bridge.
AB  - When a high voltage is applied between two beakers filled with deionized water, a
      floating bridge of water is formed in between exceeding the length of 2 cm when
      the beakers are pulled apart. Currently two theories regarding the stability of
      the floating water bridge exist, one suggesting that the tension caused by
      electric field in the dielectric medium is holding the bridge and the other
      suggesting surface tension to be responsible for the vertical equilibrium. We
      construct experiments in which the electric field and the geometry of the bridge
      are measured and compared with predictions of theories of the floating water
      bridge stability. We use a numerical simulation for estimation of the electric
      field. Our results indicate that the two forces of dielectric and surface
      tensions hold the bridge against gravity simultaneously and, having the same
      order of magnitude, neither of the two forces are negligible. In bridges with
      larger diameters, the effect of dielectric tension is slightly more in the
      vertical equilibrium than surface tension. Results show that the stability can be
      explained by macroscopic forces, regardless of the microscopic changes in the
      water structure. 

PMID- 24125357
TI  - Shape-dependent orientation of thermophoretic forces in microsystems.
AB  - It is generally acknowledged that the direction of the thermophoretic force
      acting on microparticles is largely determined by the imposed temperature
      gradient, and the shape of the microparticle has little influence on its
      direction. We show that one type of thermophoretic force, emerged due to the
      advent of microfabrication techniques, is highly sensitive to object shape, and
      it is feasible to tune force orientation via proper shape design. We reveal the
      underlying mechanism by an asymptotic analysis of the Boltzmann equation and
      point out the reason why the classical thermophoretic force is insensitive to the
      particle shape, but the force in microsystems is. The discovered phenomenon could
      find its applications in methods for microparticle manipulation and separation. 

PMID- 24125358
TI  - Electric double-layer interactions in a wedge geometry: change in contact angle
      for drops and bubbles.
AB  - In this paper, we provide a theory to pinpoint the role of electric double layer
      (EDL) interactions in governing the contact angle of an electrolyte drop on a
      charged solid in air or a bubble on a charged surface within an electrolyte
      solution. The EDL interactions are analytically solved by representing the three
      phase contact line as a wedge edge, with the wedge being formed by the solid
      liquid and the air-liquid interfaces, and calculating the corresponding Maxwell
      stresses. We demonstrate that the EDL effects induce an "electrowetting-like"
      behavior, resulting in a lowering of the contact angle. As a specific example, we
      use this model to analyze the effect of added salt on preformed surface
      nanobubbles, and find, in contrast to what has been reported earlier, that even
      for most moderate conditions, added salt may have remarkable effect in altering
      the contact angle in preformed surface nanobubbles.

PMID- 24125359
TI  - Interface dynamics of immiscible two-phase lattice-gas cellular automata: a model
      with random dynamic scatterers and quenched disorder in two dimensions.
AB  - We use a lattice gas cellular automata model in the presence of random dynamic
      scattering sites and quenched disorder in the two-phase immiscible model with the
      aim of producing an interface dynamics similar to that observed in Hele-Shaw
      cells. The dynamics of the interface is studied as one fluid displaces the other
      in a clean lattice and in a lattice with quenched disorder. For the clean system,
      if the fluid with a lower viscosity displaces the other, we show that the model
      exhibits the Saffman-Taylor instability phenomenon, whose features are in very
      good agreement with those observed in real (viscous) fluids. In the system with
      quenched disorder, we obtain estimates for the growth and roughening exponents of
      the interface width in two cases: viscosity-matched fluids and the case of
      unstable interface. The first case is shown to be in the same universality class
      of the random deposition model with surface relaxation. Moreover, while the early
      time dynamics of the interface behaves similarly, viscous fingers develop in the
      second case with the subsequent production of bubbles in the context of a complex
      dynamics. We also identify the Hurst exponent of the subdiffusive fractional
      Brownian motion associated with the interface, from which we derive its fractal
      dimension and the universality classes related to a percolation process.

PMID- 24125360
TI  - Relation between shape of liquid-gas interface and evolution of buoyantly
      unstable three-dimensional chemical fronts.
AB  - Buoyantly unstable 3D chemical fronts were seen traveling through an iodate
      arsenous acid reaction solution. The experiments were performed in channel
      reactors with rectangular cross sections, where the top of the reaction solution
      was in contact with air. A concave or convex meniscus was pinned to reactor
      lateral walls. Influence of the meniscus shape on front development was
      investigated. For the concave meniscus, an asymptotic shape of fronts holding
      negative curvature was observed. On the other hand, fronts propagating in the
      solution with the convex meniscus kept only positive curvature. Those fronts were
      also a bit faster than fronts propagating in the solution with the concave
      meniscus. A relation between the meniscus shape, flow distribution, velocity, and
      shape is discussed.

PMID- 24125362
TI  - Electric-field-induced rotation of Brownian metal nanowires.
AB  - We describe the physical mechanism responsible for the rotation of Brownian metal
      nanowires suspended in an electrolyte exposed to a rotating electric field. The
      electric field interacts with the induced charge in the electrical double layer
      at the metal-electrolyte interface, causing rotation due to the torque on the
      induced dipole and to the induced-charge electro-osmotic flow around the
      particle. Experiments demonstrate that the primary driving mechanism is the
      former of these two. Our analysis contrasts with previous work describing the
      electrical manipulation of metallic particles with electric fields, which
      neglected the electrical double layer. Theoretical values for the rotation speed
      are calculated and good agreement with experiments is found. 

PMID- 24125361
TI  - Model of dynamic self-assembly in ferromagnetic suspensions at liquid interfaces.
AB  - Ferromagnetic microparticles suspended at the interface between immiscible
      liquids and energized by an external alternating magnetic field show a rich
      variety of self-assembled structures, from linear snakes to radial asters. In
      order to obtain insight into the fundamental physical mechanisms and the overall
      balance of forces governing self-assembly, we develop a modeling approach based
      on analytical solutions of the time-averaged Navier-Stokes equations. These
      analytical expressions for the self-consistent hydrodynamic flows are then
      employed to modify effective interactions between the particles, which in turn
      are formulated in terms of the time-averaged quantities. Our method allows
      effective computational verification of the mechanisms of self-assembly and leads
      to a testable prediction, e.g., on the transitions between various patterns
      versus viscosity of the solvent. 

PMID- 24125363
TI  - Energy concentration and positional stability of sonoluminescent bubbles in
      sulfuric acid for different static pressures.
AB  - In this study we report several experimental and numerical results on the
      influence of static pressure (P_{0}) over the main parameters in single bubble
      sonoluminescence (SBSL), using a sulfuric acid aqueous solution (SA) with low
      concentrations of argon gas dissolved. Bifrequency driving was used in the
      experiments to enhance spatial stability of the bubbles. The experimental results
      were compared with simulations provided by a numerical code that models the
      radial dynamics of the bubbles. The results showed that an increase on the static
      pressure of the system shifts the Bjerknes instability threshold, allowing the
      bubble to access higher acoustic pressures (P_{Ac}^{}). Furthermore, a decrease
      in the measured ambient radius R_{0} and the calculated relative gas
      concentration c_{infinity}/c_{0} were observed. A notorious increment in the
      bubble collapse violence and energy focusing for P_{0} above 1 bar was achieved.
      These were mainly indicated by the growth of the bubble expansion ratio
      (R_{max}/R_{0}), the bubble mechanical energy density, and the maximum bubble
      wall velocity dR/dt. In agreement with the previous statement, the maximum
      temperature during the bubble collapse predicted by the model is augmented as
      well. The use of different harmonics in the ultrasound pressure field regarding
      energy focusing is also discussed. Finally, we analyzed the stability regions of
      the R_{0}-P_{Ac}^{} parameter space via numerical predictions for P_{0} above the
      measured, identifying the shape instabilities as the main limiting agent to
      obtain further energy concentration in SA systems at high static pressures.

PMID- 24125364
TI  - Theoretical investigation of a technique to produce microbubbles by a
      microfluidic T junction.
AB  - A microfluidic technique is proposed to produce microbubbles. A gaseous stream is
      injected through a T junction into a channel transporting a liquid current. The
      gas adheres to a hydrophobic strip printed on the channel surface. When the gas
      and liquid flow rates are set appropriately, a gaseous rivulet flows over that
      strip. The rivulet breaks up downstream due to a capillary pearling instability,
      which leads to a monodisperse collection of microbubbles that can be much smaller
      than the channel size. The physics of the process is theoretically investigated,
      using both full numerical simulation of the Navier-Stokes equations and a linear
      stability analysis of an infinite gaseous rivulet driven by a coflowing liquid
      stream. This stability analysis allows one to determine a necessary condition to
      get this effect in a T junction device. It also provides reasonably good
      predictions for the size of the produced microbubbles as obtained from numerical
      experiments.

PMID- 24125365
TI  - Counterexample of the magnetorotational instability in two-dimensional axial
      symmetry.
AB  - We analyze a linear perturbation scheme for a two-dimensional background plasma,
      which is rotating at a differential frequency and is embedded in a poloidal
      magnetic field. The main two assumptions of the present study, which in turn are
      related, are (i) that the plasma profile is axially symmetric, both in the
      background and in the perturbation approximation, where the azimuthal magnetic
      field is requested to vanish identically, and (ii) that the angular frequency
      depends on the magnetic surface function only, still holds in the nonstationary
      regime, which, in the steady background equilibrium, is ensured by the validity
      of the corotation theorem [V. C. A. Ferraro, Mon. Not. R. Astron. Soc. 97, 458
      (1937)]. Indeed, such a restriction of the model is rather natural and it implies
      that the azimuthal component of the linear plasma shift is reabsorbed in the
      expression for the nonstationary electric field (in principle, at any order of
      approximation) and can no longer provide a nonzero azimuthal component of the
      magnetic tension field. As a result, the magnetorotational instability is
      suppressed and the magnetic field has the effect to stabilize the plasma
      configuration with respect to the pure hydrodynamical case.

PMID- 24125366
TI  - Evaluation of slowing down of proton and deuteron beams in CH2, LiH, and Al
      partially ionized plasmas.
AB  - In this work, proton and deuteron stopping due to free and bound electrons in
      partially ionized plasma targets is evaluated. The stopping of target free
      electrons is calculated using the dielectric formalism, well described in our
      previous works. In the case of target bound electrons, a short expression to
      calculate their contribution to the stopping is used, where mean excitation
      energies are obtained by means of the Hartree-Fock method. Experiments with
      different kinds of plasmas are analyzed. For LiH plasma, estimated plasma
      stopping fits experimental data very well, within the error bars, recognizing the
      well-known enhanced plasma stopping. In the case of CH_{2} plasma, we obtain,
      from estimated ionization, that total stopping power increases when target
      electron density does. Our estimations are very similar to experimental data
      which show the same behavior with target free and bound electron density.
      Finally, in Al plasma, we compare directly our calculations with experimental
      data finding a very close agreement, where both stoppings have the same
      dependence on target ionicity. All these comparisons verify our theoretical model
      which estimates the proton or deuteron energy loss in partially ionized plasmas.

PMID- 24125367
TI  - Negative plasma potential relative to electron-emitting surfaces.
AB  - Most works on plasma-wall interaction predict that with strong electron emission,
      a nonmonotonic "space-charge-limited" (SCL) sheath forms where the plasma
      potential is positive relative to the wall. We show that a fundamentally
      different sheath structure is possible where the potential monotonically
      increases toward a positively charged wall that is shielded by a single layer of
      negative charge. No ion-accelerating presheath exists in the plasma and the ion
      wall flux is zero. An analytical solution of the "inverse sheath" regime is
      demonstrated for a general plasma-wall system where the plasma electrons and
      emitted electrons are Maxwellian with different temperatures. Implications of the
      inverse sheath effect are that (a) the plasma potential is negative, (b) ion
      sputtering vanishes, (c) no charge is lost at the wall, and (d) the electron
      energy flux is thermal. To test empirically what type of sheath structure forms
      under strong emission, a full plasma bounded by strongly emitting walls is
      simulated. It is found that inverse sheaths form at the walls and ions are
      confined in the plasma. This result differs from past particle-in-cell simulation
      studies of emission which contain an artificial "source sheath" that accelerates
      ions to the wall, leading to a SCL sheath at high emission intensity.

PMID- 24125368
TI  - Demonstration of a 13-keV Kr K-shell x-ray source at the National Ignition
      Facility.
AB  - We report 3% conversion efficiency of laser energy into Kr K-shell (~13 keV)
      radiation, consistent with theoretical predictions. This is ~10* greater than
      previous work. The emission was produced from a 4.1-mm-diameter, 4-mm-tall gas
      pipe target filled with 1.2 or 1.5 atm of Kr gas. 160 of the National Ignition
      Facility laser beams deposited ~700 kJ of 3omega light into the target in an ~140
      TW, 5.0-ns-duration square pulse. The Dante diagnostics measured ~5 TW into 4pi
      solid angle of >=12 keV x rays for ~4 ns, which includes both continuum emission
      and flux in the Kr He_{alpha} line at 13 keV.

PMID- 24125369
TI  - Collisionless energy-independent kinetic equilibria in axisymmetric magnetized
      plasmas.
AB  - The proof of existence of Vlasov-Maxwell equilibria which do not exhibit a
      functional dependence in terms of the single-particle energy is established. The
      theory deals with the kinetic treatment of multispecies axisymmetric magnetized
      plasmas, with particular reference to plasma systems which are slowly time
      varying. Aside from collisionless laboratory plasmas, the theory concerns
      important aspects of astrophysical scenarios, such as accretion-disk and coronal
      plasmas arising in the gravitational field of compact objects. Qualitative
      properties of the solution are investigated by making use of a perturbative
      kinetic theory. These concern the realization of the equilibrium kinetic
      distribution functions in terms of generalized Gaussian distributions and the
      constraints imposed by the Maxwell equations. These equilibria are shown to be
      generally non-neutral and characterized by the absence of the Debye screening
      effect. As a further application, the stability properties of these equilibria
      with respect to axisymmetric electromagnetic perturbations are addressed. This
      permits us to establish absolute stability criteria holding in such a case.

PMID- 24125370
TI  - Thermophysical properties of hydrogen-helium mixtures: re-examination of the
      mixing rules via quantum molecular dynamics simulations.
AB  - Thermophysical properties of hydrogen, helium, and hydrogen-helium mixtures have
      been investigated in the warm dense matter regime at electron number densities
      ranging from 6.02 * 10^{29} ~ 2.41 * 10^{30} m^{-3} and temperatures from 4000 to
      20000 K via quantum molecular dynamics simulations. We focus on the dynamical
      properties such as the equation of states, diffusion coefficients, and viscosity.
      Mixing rules (density matching, pressure matching, and binary ionic mixing rules)
      have been validated by checking composite properties of pure species against that
      of the fully interacting mixture derived from quantum molecular dynamics
      simulations. These mixing rules reproduce pressures within 10% accuracy, while it
      is 75% and 50% for the diffusion and viscosity, respectively. The binary ionic
      mixing rule moves the results into better agreement. Predictions from one
      component plasma model are also provided and discussed.

PMID- 24125371
TI  - Sum rules for electron-hole bilayer and two-dimensional point dipole systems.
AB  - We formulate and analyze the third-frequency-moment sum rules for the two
      dimensional (point) dipole system (2DDS) and the mass-symmetric electron-hole
      bilayer (EHB) in their strongly coupled liquid phases. The former, characterized
      by the repulsive interaction potential phi_{D}(r)=MU^{2}/r^{3} (MU is the
      electric dipole moment), reasonably well approximates the latter in the d -> 0
      limit (d is the interlayer spacing), a conjecture that is further supported by
      the findings of the present work. We explore the extent to which the in-phase sum
      rule for the closely spaced EHB may or may not reconcile with its 2DDS sum-rule
      counterpart. This is the main emphasis of the present work.

PMID- 24125372
TI  - Experimental study of fusion neutron and proton yields produced by petawatt-laser
      irradiated D2-3He or CD4-3He clustering gases.
AB  - We report on experiments in which the Texas Petawatt laser irradiated a mixture
      of deuterium or deuterated methane clusters and helium-3 gas, generating three
      types of nuclear fusion reactions: D(d,^{3}He)n, D(d,t)p, and ^{3}He(d,p)^{4}He.
      We measured the yields of fusion neutrons and protons from these reactions and
      found them to agree with yields based on a simple cylindrical plasma model using
      known cross sections and measured plasma parameters. Within our measurement
      errors, the fusion products were isotropically distributed. Plasma temperatures,
      important for the cross sections, were determined by two independent methods: (1)
      deuterium ion time of flight and (2) utilizing the ratio of neutron yield to
      proton yield from D(d,^{3}He)n and ^{3}He(d,p)^{4}He reactions, respectively.
      This experiment produced the highest ion temperature ever achieved with laser
      irradiated deuterium clusters. 

PMID- 24125373
TI  - Effects of ion mobility and positron fraction on solitary waves in weak
      relativistic electron-positron-ion plasma.
AB  - The effects of ion mobility and positron fraction on the solitary waves of the
      laser field envelope and the potential of the electrostatic field in weak
      relativistic electron-positron-ion plasma are investigated. The parameter region
      for the existence of solitary waves is obtained analytically, and a reasonable
      choice of parameters is clarified. Both cases of mobile and immobile ions are
      considered. It is found that the amplitudes of solitary waves in the former case
      are larger compared to the latter case. For small plasma density, the localized
      solitary wave solutions in terms of the approximate perturbation analytical
      method are very consistent with those by exact numerical calculations. However,
      as the plasma density increases the analytical method loses its validity more and
      more. The influence of the positron fraction on the amplitudes of solitary waves
      shows a monotonous increasing relation. The implications of our results to
      particle acceleration are also discussed briefly. 

PMID- 24125374
TI  - Thermal transparency with the concept of neutral inclusion.
AB  - The concept of the electromagnetic wave transparency is introduced into the
      thermal field. The conditions of the thermal transparency for a multilayered
      sphere with isotropic coatings, a coated spheroid with an isotropic coating, and
      a coated sphere with a radial anisotropic core or a radial anisotropic coat are
      deduced with the help of the idea of the neutral inclusion. The thermal
      transparency can be achieved by making the effective thermal conductivity of the
      composite inclusion equal to the thermal conductivity of the surrounding matrix.
      The validity of the theoretical analysis is checked by the corresponding
      simulated results, which indicate that the designed neutral inclusion can be
      transparent perfectly. A specific case of interest of the thermal transparency is
      its application to cancel the thermal stress concentration resulting from the
      existence of the inclusions in the particle (even the thermal-insulated particle)
      -reinforced composites. 

PMID- 24125375
TI  - Fracture path in an anisotropic material in the light of a friction experiment.
AB  - A slider is pulled by means of a flexible link on a flat solid surface which
      exhibits anisotropic frictional properties. The resulting trajectory of the
      slider is assessed experimentally. First, we check that the experimental results
      are in excellent agreement with a theoretical description of the problem based on
      an expression of the frictional forces. Second, we point out that the trajectory
      of the slider can be recovered by the use of a "maximum of energy release rate"
      criterion which is generally used to predict the path of a fracture even if the
      validity of the principle is difficult to verify in the latter complex systems. 

PMID- 24125376
TI  - Radiation reaction on a classical charged particle: a modified form of the
      equation of motion.
AB  - We present and numerically solve a modified form of the equation of motion for a
      charged particle under the influence of an external force, taking into account
      the radiation reaction. This covariant equation is integro-differential, as Dirac
      Rohrlich's, but has several technical improvements. First, the equation has the
      form of Newton's second law, with acceleration isolated on the left hand side and
      the force depending only on positions and velocities: Thus, the equation is
      linear in the highest derivative. Second, the total four-force is by construction
      perpendicular to the four-velocity. Third, if the external force vanishes for all
      future times, the total force and the acceleration automatically vanish at the
      present time. We show the advantages of this equation by solving it numerically
      for several examples of external force.

PMID- 24125377
TI  - Nonlinear phasing and dephasing of three-wave mixing of acoustic guided waves.
AB  - We measure the propagation of guided acoustic waves in a nonlinear three-wave
      mixing experiment in a water-filled steel pipe. These waves exhibit a predicted
      phasing-dephasing behavior as a function of propagation distance due to the
      underlying velocity dispersion between the fundamentals and the nonlinearly
      generated waves. We extract the dimensionless nonlinear parameter, beta, which is
      weakly frequency dependent. 

PMID- 24125378
TI  - Beating the Rayleigh limit: orbital-angular-momentum-based super-resolution
      diffraction tomography.
AB  - This paper reports a super-resolution imaging approach based on orbital-angular
      momentum diffraction tomography (OAM-DT), which makes an important breakthrough
      on the Rayleigh limit associated with conventional diffraction tomography (DT)
      technique. It is well accepted that orbital-angular momentum (OAM) provides
      additional electromagnetic degrees of freedom. This concept has been widely
      applied in science and technology. In this paper we revisit the DT problem
      extended with OAM, and demonstrate theoretically and numerically that there is no
      physical limit on imaging resolution with OAM-DT. The physical mechanism behind
      it is that either the near field or superoscillation of the transmitter is
      employed to super-resolve probed objects. This super-resolution OAM-DT imaging
      paradigm does not require near-field measurement, a subtle focusing lens, or
      complicated postprocessing, etc., thus providing an approach to realize the wave
      field imaging of universal objects with subwavelength resolution.

PMID- 24125379
TI  - Filtering schemes in the quantum-classical Liouville approach to nonadiabatic
      dynamics.
AB  - We study a number of filtering schemes for the reduction of the statistical error
      in nonadiabatic calculations by means of the quantum-classical Liouville
      equation. In particular, we focus on a scheme based on setting a threshold value
      on the sampling weights, so that when the threshold is overcome the value of the
      weight is reset, and on another approach which prunes the ensemble of the allowed
      nonadiabatic transitions according to a generalized sampling probability. Both
      methods have advantages and drawbacks, however, their combination drastically
      improves the performance of an algorithm known as the sequential short-time step
      propagation [MacKernan et al., J. Phys: Condens. Matter 14, 9069 (2002)], which
      is derived from a simple first order expansion of the quantum-classical
      propagator. Such an algorithm together with the combined filtering procedures
      produce results that compare very well with those obtained by means of
      numerically accurate path integral quantum calculations for the spin-boson model,
      even for intermediate and strong coupling regimes.

PMID- 24125381
TI  - Efficient simulation of the random-cluster model.
AB  - The simulation of spin models close to critical points of continuous phase
      transitions is heavily impeded by the occurrence of critical slowing down. A
      number of cluster algorithms, usually based on the Fortuin-Kasteleyn
      representation of the Potts model, and suitable generalizations for continuous
      spin models have been used to increase simulation efficiency. The first algorithm
      making use of this representation, suggested by Sweeny in 1983, has not found
      widespread adoption due to problems in its implementation. However, it has been
      recently shown that it is indeed more efficient in reducing critical slowing down
      than the more well-known algorithm due to Swendsen and Wang. Here, we present an
      efficient implementation of Sweeny's approach for the random-cluster model using
      recent algorithmic advances in dynamic connectivity algorithms.

PMID- 24125382
TI  - Improved treatments for general boundary conditions in the lattice Boltzmann
      method for convection-diffusion and heat transfer processes.
AB  - In spite of the increasing applications of the lattice Boltzmann method (LBM) in
      simulating various flow and transport systems in recent years, complex boundary
      conditions for the convection-diffusion and heat transfer processes in LBM have
      not been well addressed. In this paper, we propose an improved bounce-back method
      by using the midpoint concentration value to modify the bounced-back density
      distribution for LBM simulations of the concentration field. An accurate finite
      difference scheme in the normal boundary direction has also been introduced for
      gradient boundary conditions. Compared with existing boundary methods, our method
      has a simple algorithm and can easily deal with boundaries with general
      geometries, motions, and surface conditions (the Dirichlet, Neumann, and mixed
      conditions). Carefully designed simulations are performed to examine the capacity
      and accuracy of this proposed boundary method. Simulation results are compared
      with those from theory and a representative boundary method, and an improved
      performance is observed. We have also simulated the effect of reference velocity
      on global accuracy to examine the performance of our model in preserving the
      fundamental Galilean invariance. These boundary treatments for concentration
      boundary conditions can be readily applied to other processes such as heat
      transfer systems. 

PMID- 24125380
TI  - Lattice-Boltzmann-based two-phase thermal model for simulating phase change.
AB  - A lattice Boltzmann (LB) method is presented for solving the energy conservation
      equation in two phases when the phase change effects are included in the model.
      This approach employs multiple distribution functions, one for a
      pseudotemperature scalar variable and the rest for the various species. A
      nonideal equation of state (EOS) is introduced by using a pseudopotential LB
      model. The evolution equation for the pseudotemperature variable is constructed
      in such a manner that in the continuum limit one recovers the well known
      macroscopic energy conservation equation for the mixtures. Heats of reaction, the
      enthalpy change associated with the phase change, and the diffusive transport of
      enthalpy are all taken into account; but the dependence of enthalpy on pressure,
      which is usually a small effect in most nonisothermal flows encountered in
      chemical reaction systems, is ignored. The energy equation is coupled to the LB
      equations for species transport and pseudopotential interaction forces through
      the EOS by using the filtered local pseudotemperature field. The proposed scheme
      is validated against simple test problems for which analytical solutions can
      readily be obtained.

PMID- 24125383
TI  - Discrete unified gas kinetic scheme for all Knudsen number flows: low-speed
      isothermal case.
AB  - Based on the Boltzmann-BGK (Bhatnagar-Gross-Krook) equation, in this paper a
      discrete unified gas kinetic scheme (DUGKS) is developed for low-speed isothermal
      flows. The DUGKS is a finite-volume scheme with the discretization of particle
      velocity space. After the introduction of two auxiliary distribution functions
      with the inclusion of collision effect, the DUGKS becomes a fully explicit scheme
      for the update of distribution function. Furthermore, the scheme is an asymptotic
      preserving method, where the time step is only determined by the Courant
      Friedricks-Lewy condition in the continuum limit. Numerical results demonstrate
      that accurate solutions in both continuum and rarefied flow regimes can be
      obtained from the current DUGKS. The comparison between the DUGKS and the well
      defined lattice Boltzmann equation method (D2Q9) is presented as well.

PMID- 24125384
TI  - Force-moment line element method for flexible slender bodies in Stokes flow.
AB  - The hydrodynamics of flexible slender bodies in Stokes flow is studied by taking
      into account the fluid-structure interaction through both forces and coupled
      moments. The fluid subjected to line sources of forces and moments is described
      by using integral equations. Meanwhile, the flexible slender body is modeled
      using finite beam elements. The two sides are linked through interfacial
      continuity conditions. Upon discretization, it results in a higher-order line
      element method for efficient and accurate solution of slender-body hydrodynamics.
      Four examples are presented to demonstrate the validity and efficiency of the
      present method: (a) hydrodynamics of a flexible slender rod subjected to a torque
      at one end, (b) hydrodynamics of a flexible slender rod subjected to a bending
      moment at one end, (c) hydrodynamics of a flexible slender rod subjected to a
      cyclic force, and (d) hydrodynamics of a flexible slender rod with a magnetized
      head within a rotating magnetic field. Examples (a) and (b) may serve as
      benchmark solutions and examples (c) and (d) show how planar and spiral waves can
      be excited in a slender body. 

PMID- 24125385
TI  - Order-disorder quantum phase transition in the quasi-one-dimensional spin-1/2
      collinear antiferromagnetic Heisenberg model.
AB  - The ground-state properties of the quasi-one-dimensional spin-1/2
      antiferromagnetic Heisenberg model is investigated by using a variational method.
      Spins on chains along the x direction are antiferromagnetically coupled with
      exchange J>0, while spins between chains in the y direction are coupled either
      ferromagnetically (J' < 0) or antiferromagnetically (J' > 0). The staggered and
      the colinear antiferromagnetic magnetizations are computed and their dependence
      on the anisotropy parameter lambda=|J'|/J is analyzed. It is found that an
      infinitesimal interchain coupling parameter is sufficient to stabilize a long
      range order with either a staggered magnetization m_{s} (J' > 0) or a colinear
      antiferromagnetic magnetization m_{caf} (J' < 0), both behaving as ?lambda1/2 for
      lambda -> 0.

PMID- 24125386
TI  - Restricted solid-on-solid model with a proper restriction parameter N in 4+1
      dimensions.
AB  - A restricted solid-on-solid growth model is studied for various restriction
      parameters N in d=4+1 dimensions. The interface width W grows as t^{beta} with
      beta=0.158 +/- 0.006 and W follows W~L{alpha} at saturation with alpha=0.273 +/-
      0.009, where L is the system size. The dynamic exponent z~1.73 is obtained from
      the relation z=alpha/beta. The estimated exponents satisfy the scaling relation
      alpha+z=2 very well. Our results indicate that the upper critical dimension of
      the Kardar-Parisi-Zhang equation is larger than d=4+1 dimensions. With a proper
      choice of the restriction parameter N, we can reduce the discrete effect of the
      height to the width and obtain the values of the exponents accurately.

PMID- 24125387
TI  - Elastic models of the fast traps of carnivorous Dionaea and Aldrovanda.
AB  - The carnivorous aquatic waterwheel plant (Aldrovanda vesiculosa L.) and the
      closely related terrestrial Venus flytrap (Dionaea muscipula Sol. ex J. Ellis)
      both feature elaborate snap-traps, which shut after reception of an external
      mechanical stimulus by prey animals. Although Aldrovanda is usually considered a
      miniature aquatic Dionaea, the shutting mechanisms of the two plants differ quite
      markedly. The fast shutting of Aldrovanda is indeed based on a simple swelling or
      shrinking mechanism, while the movement of Dionaea's traps is accelerated by the
      snap-buckling of the lobes. The purpose of this Brief Report is to describe
      several key improvements to the elastic models that have recently been introduced
      to elucidate these movements [Poppinga and Joyeux, Phys. Rev. E 84, 041928
      (2011)]. In particular, a precise mechanism for the action of the motor cells of
      Aldrovanda is proposed, the facts that the opening of the leaves of Dionaea is an
      irreversible mechanism based on growth and that the strain field is anisotropic
      and much smaller on the inner than on the outer surface of the leaves during
      shutting are taken properly into account, and a more accurate formula for
      calculating mean curvatures is used. The improvements brought to the model are
      described in detail and the physical consequences of these improvements are
      discussed.

PMID- 24125388
TI  - Phase-field approach to chemotactic driving of neutrophil morphodynamics.
AB  - To simulate the motion of neutrophils and their morphodynamics in response to
      chemical cues, we construct a model based on the phase-field method utilizing a
      description with a free-energy functional and associated dynamics which captures
      the basic features of the phenomenon. We additionally incorporate spatial sensing
      by introducing an auxiliary field which depicts the polymerization of the region
      of the cell facing the highest concentration of the chemical attractant.

PMID- 24125389
TI  - Dynamical tunneling of a Bose-Einstein condensate in periodically driven systems.
AB  - We report measurements of dynamical tunneling rates of a Bose-Einstein condensate
      across a barrier in classical phase space. The atoms are initially prepared in
      quantum states that extend over a classically regular island region. We focus on
      the specific system of quantum accelerator modes of the kicked rotor in the
      presence of gravity. Our experimental data is supported by numerical simulations
      taking into account imperfections mainly from spontaneous emission. Furthermore,
      we predict experimentally accessible parameter ranges over which direct tunneling
      could be readily observed if spontaneous emission was further suppressed.
      Altogether, we provide a proof-of-principle for the experimental accessibility of
      dynamical tunneling rates in periodically driven systems. 

PMID- 24125390
TI  - Oscillation death in diffusively coupled oscillators by local repulsive link.
AB  - A death of oscillation is reported in a network of coupled synchronized
      oscillators in the presence of additional repulsive coupling. The repulsive link
      evolves as an averaging effect of mutual interaction between two neighboring
      oscillators due to a local fault and the number of repulsive links grows in time
      when the death scenario emerges. Analytical condition for oscillation death is
      derived for two coupled Landau-Stuart systems. Numerical results also confirm
      oscillation death in chaotic systems such as a Sprott system and the Rossler
      oscillator. We explore the effect in large networks of globally coupled
      oscillators and find that the number of repulsive links is always fewer than the
      size of the network.

PMID- 24125391
TI  - Relaxation and intermediate asymptotics of a rectangular trench in a viscous
      film.
AB  - The surface of a thin liquid film with nonconstant curvature flattens as a result
      of capillary forces. While this leveling is driven by local curvature gradients,
      the global boundary conditions greatly influence the dynamics. Here, we study the
      evolution of rectangular trenches in a polystyrene nanofilm. Initially, when the
      two sides of a trench are well separated, the asymmetric boundary condition given
      by the step height controls the dynamics. In this case, the evolution results
      from the leveling of two noninteracting steps. As the steps broaden further and
      start to interact, the global symmetric boundary condition alters the leveling
      dynamics. We report on full agreement between theory and experiments for the
      capillary-driven flow and resulting time dependent height profiles, a crossover
      in the power-law dependence of the viscous energy dissipation as a function of
      time as the trench evolution transitions from two noninteracting to interacting
      steps, and the convergence of the profiles to a universal self-similar attractor
      that is given by the Green's function of the linear operator describing the
      dimensionless linearized thin film equation. 

PMID- 24125392
TI  - Divergence of the Stark collision operator at large impact parameters in plasma
      spectroscopy models.
AB  - The divergence that occurs at large impact parameters in Stark collision
      operators is examined for low-density hydrogen plasmas. In a previous work [J.
      Rosato, H. Capes, and R. Stamm, Phys. Rev. E 86, 046407 (2012)], we showed that
      the correlations between a radiating atom and the charged particles surrounding
      it affect the mean evolution of the atom, resulting in a mitigation of the Stark
      broadening near the line center. In this work, we examine the physical mechanism
      underlying this mitigation with an approach inspired from the standard
      semiclassical impact model. Our approach accounts for the atom-perturber
      correlations in a simple fashion, through a cutoff at large impact parameters,
      and embraces the impact model in the weakly coupled plasma limit. Comparisons
      with numerical simulations are performed and indicate a good agreement.

PMID- 24125393
TI  - Finite-depth capillary-gravity dromions.
AB  - It is known that the governing equations for the evolution of the envelope of
      weakly nonlinear capillary-gravity wave packets, the so-called Davey-Stewartson
      equation, admit dromion solutions in the limit of shallow water and strong
      surface tension, i.e., when kh?1 and the Bond number (Bo) =T/rhogh^{2}>1/3 (where
      T is the surface tension coefficient and h the water depth). Here we show that
      capillary-gravity dromions exist beyond this limit for a broad range of finite
      water depths, i.e., for kh >= O(1), as well as for subcritical Bond numbers,
      i.e., for Bo < 1/3.

PMID- 24125394
TI  - Initial value problems of cylindrical electromagnetic waves propagation in a
      nonlinear nondispersive medium.
AB  - We introduce a simple method to estimate the accuracy of exact solutions under
      initial value conditions proposed by Petrov and Kudrin [Phys. Rev. Lett. 104,
      190404 (2010)]. We demonstrate that even for a sufficiently weak nonlinearity,
      the initial value condition difference between linear and nonlinear case may be
      evident. Our result may be used as a criterion of employing the exact solution to
      deal with initial value problems of cylindrical electromagnetic wave propagation
      in a nonlinear nondispersive medium.

PMID- 24125395
TI  - Comment on "constructing quantum games from nonfactorizable joint probabilities".
AB  - In the paper [Phys. Rev. E 76, 061122 (2007)], the authors presented a way of
      playing 2 * 2 games so that players were able to exploit nonfactorizable joint
      probabilities respecting the nonsignaling principle (i.e., relativistic
      causality). We are going to prove, however, that the scheme does not generalize
      the games studied in the commented paper. Moreover, it allows the players to
      obtain nonclassical results even if the factorizable joint probabilities are
      used.

PMID- 24125396
TI  - In vitro and in vivo effects of human monocytes and their subsets on new vessel
      formation.
AB  - OBJECTIVE: Human monocytes can be divided into CD16(-) monocytes and CD16(+)
      monocytes. Studies in mice suggested differential effects of monocyte subsets
      during new vessel formation. METHODS: The functional role of human monocyte
      subsets in neovascularization processes was investigated. For in vivo
      experiments, nude mice underwent unilateral hindlimb ischemia surgery before
      being injected with either total monocytes, CD16(-) monocytes or CD16(+)
      monocytes isolated from healthy individuals. RESULTS: In vitro, cytokine array
      analysis demonstrated that monocytes release numerous angiogenic cytokines, some
      of which were differentially expressed in monocyte subsets. Sprout length was
      enhanced in EC spheroids being cultured in conditioned medium obtained from total
      monocytes and, to a lesser extent, also in supernatants of CD16(-) monocytes.
      Laser Doppler perfusion imaging up to day 28 after surgery revealed a trend
      toward improved revascularization in mice treated with monocytes, but no
      significant differences between monocyte subsets. Histological analyses four
      weeks after surgery showed an increased arteriole size in mice having received
      CD16(+) monocytes, whereas the number of capillaries did not significantly differ
      between groups. CONCLUSIONS: Our findings suggest additive and differential
      effects of monocyte subsets during neovascularization processes, possibly due to
      an altered secretion of angiogenic factors and their paracrine capacity to
      stimulate new vessel formation.

PMID- 24125398
TI  - Use, Knowledge, and Attitudes Toward Evidence-Based Practice Among Nursing Staff.

PMID- 24125397
TI  - Testing for the multivariate stochastic order among ordered experimental groups
      with application to dose-response studies.
AB  - The comparison of two or more ordered experimental groups based on multivariate
      data is common in a variety of applications such as toxicology, clinical trials
      and drug development, to name just a few. In this article, we develop a
      nonparametric methodology for analyzing such data. In particular we propose a
      global K sample nonparametric test for order among vector valued outcomes. The
      testing procedure can also be used in a post-hoc fashion to answer questions
      about the ordering of subgroups and/or single outcomes within any subset of
      experimental groups. Such a methodology does not currently exist. In contrast
      with standard methodology such as multivariate analysis of variance (MANOVA), and
      its nonparametric analogues, we do not assume that the groups differ only by a
      location parameter or that the components of the response vector have the same
      marginal distributions between and across groups, that is, we allow for the shape
      of the distribution to change across groups. We emphasize that our test compares
      the outcome distributions, not just their mean tendencies, and explicitly
      incorporates and exploits the order constraints. Consequently it is more powerful
      than the existing unordered tests. The methodology is illustrated using
      genotoxicity data where the effect of hydrogen peroxide exposure on damage to DNA
      is evaluated using a comet assay.

PMID- 24125399
TI  - Video-assisted palatopharyngeal surgery: a model for improved education and
      training.
AB  - Objective : The learning process for intraoral procedures is arguably more
      difficult than for other surgical procedures because of the assistant's severely
      limited visibility. Consequently, trainees may not be able to adequately see and
      follow all steps of the procedure, and attending surgeons may be less willing to
      entrust trainees with critical portions of the procedure. In this report, we
      propose a video-assisted approach to intraoral procedures that improves lighting,
      visibility, and potential for effective education and training. Design :
      Technical report (idea/innovation). Setting : Tertiary referral hospital.
      Patients : Children with cleft palate and velopharyngeal insufficiency requiring
      surgery. Interventions : Video-assisted palatoplasty, sphincteroplasty, and
      pharyngoplasty. Main Outcome Measures : Qualitative and semiquantitative
      educational outcomes, including learner perception regarding "real-time" (video
      assisted surgery) and "non-real-time" (video-library-based) surgical education.
      Results : Trainees were strongly in favor of the video-assisted modality in "real
      time" surgical training. Senior trainees identified more opportunities in which
      they had been safely entrusted to perform critical portions of the procedure,
      corresponding with satisfaction with the learning process scores, and they showed
      greater comfort/confidence scores related to performing the procedure under
      supervision and alone. Conclusions : Adoption of the video-assisted approach can
      be expected to markedly improve the learning curve for surgeons in training. This
      is now standard practice at our institution. We are presently conducting a full
      educational technology assessment to better characterize the effect on knowledge
      acquisition and technical improvement. 

PMID- 24125400
TI  - Direct and indirect effects of climate change on the risk of infection by water
      transmitted pathogens.
AB  - Climate change is likely to affect the infectious disease burden from exposure to
      pathogens in water used for drinking and recreation. Effective intervention
      measures require quantification of impacts of climate change on the distribution
      of pathogens in the environment and their potential effects on human health.
      Objectives of this systematic review were to summarize current knowledge
      available to estimate how climate change may directly and indirectly affect
      infection risks due to Campylobacter, Cryptosporidium, norovirus, and Vibrio.
      Secondary objectives were to prioritize natural processes and interactions that
      are susceptible to climate change and to identify knowledge gaps. Search
      strategies were determined based on a conceptual model and scenarios with the
      main emphasis on The Netherlands. The literature search resulted in a large
      quantity of publications on climate variables affecting pathogen input and
      behavior in aquatic environments. However, not all processes and pathogens are
      evenly covered by the literature, and in many cases, the direction of change is
      still unclear. To make useful predictions of climate change, it is necessary to
      combine both negative and positive effects. This review provides an overview of
      the most important effects of climate change on human health and shows the
      importance of QMRA to quantify the net effects. 

PMID- 24125401
TI  - Effects of calcium intake on the cardiovascular system in postmenopausal women.
AB  - The use of calcium supplements for the prevention of complications of
      osteoporosis has significantly increased during the last years. The effects of
      calcium intake in postmenopausal women on cardiovascular parameters such as blood
      pressure, serum lipids and cardiovascular events are controversial. Even though
      transient beneficial effects of calcium supplementation have been reported,
      especially in women with low dietary calcium intake, their long-term outcomes are
      inconclusive. Only a very few studies investigating serum lipids in
      postmenopausal women have been described and these showed significant increases
      in high-density lipoprotein and high-density lipoprotein to low-density
      lipoprotein ratio. With regards to cardiovascular events in this population group
      adverse effects have been reported on the rates of myocardial infarction and
      stroke with increased calcium intake by some authors, however, others described
      no effects or even beneficial outcomes. We present a review of the current
      literature which provides a balanced summary of the possible beneficial and
      adverse effects of calcium intake in postmenopausal women on cardiovascular
      parameters. Taking into account the modest effect of calcium supplementation in
      reducing fracture rates, a reassessment of the role, benefits and adverse effects
      of calcium supplements should be conducted in postmenopausal women. 

PMID- 24125402
TI  - Comparison of the effect of simvastatin versus simvastatin/ezetimibe versus
      rosuvastatin on markers of inflammation and oxidative stress in subjects with
      hypercholesterolemia.
AB  - OBJECTIVES: Statins may exhibit anti-inflammatory and antioxidant effects.
      Whether different statins at equivalent doses or the combination of low-dose
      statin with ezetimibe have comparable anti-inflammatory and antioxidant effects
      is unknown. The aim of this study was to compare the effects of simvastatin,
      simvastatin/ezetimibe or rosuvastatin at equivalent low-density lipoprotein
      cholesterol lowering doses on inflammation and oxidative stress indices in
      subjects with hypercholesterolemia. METHODS: This was a pre-specified analysis of
      a prospective, randomized, open-label, blinded endpoint (PROBE) study. We
      enrolled one hundred and fifty three (n = 153) hypercholesterolemic subjects who
      were randomized to receive simvastatin 40 mg or simvastatin/ezetimibe 10/10 mg or
      rosuvastatin 10 mg daily. Plasma 8-Epi prostaglandin F2 alpha (8-epiPGF2a),
      oxidized LDL (oxLDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2)
      activity and mass were measured at baseline and following 12 weeks of treatment.
      RESULTS: A significant reduction in plasma 8-isoprostane and oxLDL levels was
      observed in all treatment groups [by 10%, 8% and 6% (p < 0.05 compared with
      baseline) and 41%, 40% and 39% (p < 0.001 compared with baseline) in simvastatin,
      simvastatin/ezetimibe and rosuvastatin groups, respectively]. In all treatment
      groups a significant reduction in total plasma Lp-PLA2 activity and mass was
      observed (by 36%, 31% and 38% and 36%, 32% and 32% for simvastatin,
      simvastatin/ezetimibe and rosuvastatin, respectively, p < 0.001 compared with
      baseline). No intergroup differences were observed. CONCLUSIONS: Simvastatin 40
      mg, simvastatin/ezetimibe 10/10 mg and rosuvastatin 10 mg significantly reduced 8
      epiPGF2a, oxLDL and Lp-PLA2 activity and mass to a similar extent.

PMID- 24125403
TI  - Appreciating the local and systemic effects of exercise training on vascular
      health.

PMID- 24125404
TI  - Seropositivity to herpes simplex virus type 2, but not type 1 is associated with
      premature cardiovascular diseases: a population-based cross-sectional study.
AB  - OBJECTIVE: Thirty-five years after herpesviruses were suggested to induce
      atherosclerosis sero-epidemiological evidence on Herpes Simplex Viruses (HSV)
      remains sparse and controversial. We aimed to investigate the relationship
      between HSV-1 and HSV-2 infections and cardiovascular diseases (CVD). METHODS AND
      RESULTS: A population-based cross-sectional study was conducted among 14,415
      participants (mean age 34.3 years, range 20-49) of the National Health and
      Nutrition Examination Survey 1999-2010. Serum IgG-antibodies to HSV were measured
      by enzymatic immunodot assay and CVD were self-reported. CVD prevalence was 1.8%;
      51.3% of participants were infected with HSV-1, 7.5% with HSV-2, and 15.2% with
      both. After adjusting for demographics, socioeconomic status, comorbidities, STD,
      and CVD risk factors, seropositivity to HSV-2 was positively associated with CVD
      (Odds ratio [OR] 1.56, 95% confidence interval [CI]: 1.09-2.21, P = 0.014), but
      not with HSV-1 (OR 1.13, 95% CI: 0.79-1.62). CONCLUSION: HSV-2 may be associated
      with premature CVD, but not HSV-1.

PMID- 24125405
TI  - Chronic HCV infection is a risk factor of ischemic stroke.
AB  - OBJECTIVES: Cerebrovascular diseases are leading cause of death worldwide. Plaque
      rupture and embolization account for one-third of ischemic stroke. The causes are
      not fully known, but inflammation plays a pathogenic role. Recently, HCV
      infection has been identify as risk of atherosclerosis. HCV replicates within
      carotid plaques and brain endothelia cells; moreover, HCV patients showed higher
      levels of inflammation. Thus, we hypothesized that subjects carrying HCV are at
      higher risk of stroke. Accordingly, we evaluated prevalence and role of HCV
      infection in patients with stroke. METHODS: A priori sample size was calculated.
      Overall, 820 consecutive patients were enrolled, 123 with stroke and, as control,
      697 age- and gender-matched (295 with COPD; 402 with diseases other than HCV
      associated). Patients were evaluated for HCV and conventional risk of stroke.
      RESULTS: Prevalence of HCV was higher in patients with stroke than that observed
      in control (26.8% vs. 6.6%, p = 0.0001). An analysis of stroke patients showed
      that those HCV positive were younger (p = 0.017) had lower serum levels of
      cholesterol (p = 0.001), triglycerides (p = 0.045), and higher serum levels of
      inflammation markers (ESR, p = 0.001; CRP, p = 0.0001; fibrinogen, p = 0.012). A
      multivariate analysis showed that HCV infection was an independent risk factor of
      stroke (O.R. 2.04, 95% C.I. 1.69-2.46; p = 0.0001). A secondary analysis showed
      that HCV patients had higher (p = 0.031) prevalence of past ischemic heart
      disease. CONCLUSIONS: HCV infected patients are at higher and earlier risk of
      stroke. Inflammation is a key mediator. Clinicians in clinical practice and
      researchers in future trials should take into account these new findings.

PMID- 24125406
TI  - Everolimus: sidekick against atherosclerosis?

PMID- 24125407
TI  - Urokinase-type plasminogen activator (uPA) modulates monocyte-to-macrophage
      differentiation and prevents Ox-LDL-induced macrophage apoptosis.
AB  - OBJECTIVE: Monocyte-to-macrophage differentiation and macrophage death play a
      pivotal role in atherogenesis. uPA and its receptor uPAR are expressed in
      atherosclerotic lesion macrophages and contribute to atherosclerosis progression.
      In the present study we investigated the effect and mechanisms of action of uPA
      on monocyte-to-macrophage differentiation and on macrophage apoptotic death.
      METHODS AND RESULTS: The number of mouse peritoneal macrophages (MPM) harvested
      from uPAR-deficient (uPAR(-/-)) mice was significantly lower by 30% in comparison
      to control C57BL/6 mice. In vitro, uPA intensified PMA-induced THP-1 monocyte
      differentiation, as determined by increased expression of the macrophage marker
      CD36. This effect was mediated via G1 arrest, downregulation of G2/S phase and
      inhibition of PMA-induced cell death. uPA attenuated MonoMac6 (MM6) macrophage
      like cell line apoptosis induced by oxidized LDL (Ox-LDL) and by thapsigargin
      (inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPase), but not by
      staurosporine (protein kinase inhibitor), suggesting that uPA antiapoptotic
      activity is Ca(2+)-independent, but involves a kinase activation. The
      antiapoptotic activity of uPA was dependent on the presence of uPAR, and it
      involved ERK1/2 activation-dependent downregulation of the proapoptotic protein
      Bim in macrophages stimulated with Ox-LDL. CONCLUSIONS: The present study
      demonstrates, for the first time, that uPA stimulates the differentiation of
      monocytes into macrophages and attenuates Ox-LDL-induced macrophage apoptotic
      death via ERK1/2 activation-dependent Bim downregulation. These processes may
      result in prolonged macrophage survival in the lesion, increased lesion
      cellularity, and eventually necrosis, which accelerates lesion development.

PMID- 24125408
TI  - Contribution of the WHHL rabbit, an animal model of familial
      hypercholesterolemia, to elucidation of the anti-atherosclerotic effects of
      statins.
AB  - This year marks the 40th year since the discovery of a mutant rabbit showing
      spontaneous hyperlipidemia, which is the proband of the Watanabe heritable
      hyperlipidemic (WHHL) rabbit strain, an animal model of familial
      hypercholesterolemia, and the first statin, a general term for inhibitors of 3
      hydroxy-3-methylglutaryl CoA reductase, a rate limiting enzyme in cholesterol
      biosynthesis. Nowadays, statins are the primary drug of choice for treating
      cardiovascular disease. Although several reviews have described clinical trials
      and in vitro studies of statins, the anti-atherosclerotic effects of statins on
      animal models have not been comprehensively reviewed. This review summarized the
      contribution of WHHL rabbits to elucidating the anti-atherosclerotic effects of
      statins in vivo. Studies using WHHL rabbits verified that statins suppress plaque
      destabilization by reducing unstable components (foam cells derived from
      macrophages, foam cell debris, and extracellular lipid accumulation), preventing
      smooth muscle cell reductions, and increasing the collagen content of plaques. In
      addition, the expression of matrix metalloproteinases and tissue factor are
      decreased in intimal macrophages by statin treatment. Lipid-lowering effects of
      statins alter plaque biology by reducing the proliferation and activation of
      macrophages, a prominent source of the molecules responsible for plaque
      instability and thrombogenicity. Although statins remain the standard treatment
      for cardiovascular disease, new therapeutics are eagerly awaited. WHHL rabbits
      will continue to contribute to the development of therapeutics.

PMID- 24125409
TI  - Soluble ST2 levels are not associated with secondary cardiovascular events and
      vulnerable plaque phenotype in patients with carotid artery stenosis.
AB  - OBJECTIVE: Soluble ST2 (sST2), a novel biomarker predictive for heart disease,
      has recently been shown associated with the progression of atherosclerotic
      disease in a mouse model. The present study was designed to assess sST2 plasma
      levels in patients scheduled for carotid endarterectomy and relate it with the
      occurrence of adverse cardiovascular events during follow-up. In addition, sST2
      levels were associated to patient clinical data and atherosclerotic plaque
      characteristics. METHODS AND RESULTS: Plasma sST2 levels were measured in 391
      patients who underwent carotid endarterectomy and were subsequently followed for
      3 years. Primary composite endpoint was the occurrence of an adverse
      cardiovascular event. At baseline, no differences were observed in sST2 levels
      between asymptomatic (n = 75) and symptomatic (n = 316) patients (85 [49-122]
      versus 90 [58-137] pg/ml, p = 0.263). Soluble ST2 plasma levels did not differ
      between patients who experienced a secondary manifestation of cardiovascular
      disease and patients who remained free of symptoms (90 [60-129] versus 88 [46
      140] pg/ml, p = 0.519). There was no association between sST2 levels and any of
      the following plaque characteristics: size of a lipid core, degree of
      calcification, number of macrophages or smooth muscle cells, amount of collagen
      and number of microvessels. CONCLUSIONS: Soluble ST2 plasma levels have no
      predictive value for future cardiovascular events in patients with significant
      carotid artery stenosis. In addition, we did not observe an association between
      plasma sST2 levels and the histopathological features of a rupture prone plaque.
      This study does not provide supportive evidence that sST2 reflects a progressive
      state of advanced atherosclerotic disease.

PMID- 24125411
TI  - Nuts and not olive oil decrease small and dense LDL: results from the PREDIMED
      Study.

PMID- 24125410
TI  - Menopause, complement, and hemostatic markers in women at midlife: the Study of
      Women's Health Across the Nation.
AB  - OBJECTIVE: To evaluate whether higher circulating levels of complement proteins
      C3 and C4 are associated with menopausal status and with hemostatic/thrombus
      formation markers (circulating factor VII (factor VIIc), fibrinogen, plasminogen
      activator inhibitor-1 (PAI-1) and tissue plasminogen activator antigen (tPA-ag))
      in a sample of midlife women. METHODS AND RESULTS: A total of 100 women (50 late
      peri-/postmenopausal and 50 pre-/early peri- menopausal women) from the Study of
      Women's Health Across the Nation (SWAN) Pittsburgh site were included in the
      present analysis. Factor VIIc and PAI-1 were log transformed. Linear regression
      was used for analysis. The mean age of the study participants was 50.5 +/- 2.6
      years with 73% were Caucasian and 27% were African American. C3 but not C4 was
      significantly higher in postmenopausal women compared to premenopausal women (P
      value = 0.03), adjusting for age, race and BMI. In final model (adjusting for
      age, race, BMI and menopausal status), C3 was associated with higher levels of
      log PAI-1 (P value = 0.0009) and tPA-ag (P value = 0.0003), while C4 was
      associated with higher levels of log factor VIIc (P value = 0.04) and fibrinogen
      (P value = 0.005). CONCLUSIONS: These data suggest that C3 and C4 may be related
      to blood clots via their associations with hemostatic markers and that C3 is
      related to menopausal status. Complement proteins C3 and C4 could be possible
      pathways by which postmenopausal women are at higher risk of atherosclerosis and
      cardiovascular related events. It is important to replicate these findings in a
      larger sample size.

PMID- 24125412
TI  - Baseline serum uric acid level as a predictor of cardiovascular disease related
      mortality and all-cause mortality: a meta-analysis of prospective studies.
AB  - OBJECTIVE: Serum uric acid (SUA) levels have been used to predict cardiovascular
      and all-cause mortality event, but the data have yielded conflicting results. We
      investigated whether SUA was an independent predictor for cardiovascular or all
      cause mortality with prospective studies by meta-analysis. METHODS: Pubmed and
      Embase were searched without language restrictions for publications available
      till April 2013. Only prospective studies on cardiovascular or all-cause
      mortality related to SUA levels were included. Pooled adjust relative risk (RR)
      and corresponding 95% confidence intervals (CI) were calculated separately for
      the highest vs. lowest category or the lowest vs. middle category. RESULTS: For
      the highest SUA, eleven studies with 172,123 participants were identified and
      analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI
      1.09-1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19-1.57). Subgroup
      analyses showed that elevated SUA significantly increase the risk of all-cause
      mortality among men (RR 1.23; 95% CI 1.08-1.42), but not in women (RR 1.05; 95%
      CI 0.79-1.39). Risk of cardiovascular mortality appeared to be more pronounced
      among women (RR 1.35; 95% CI 1.06-1.72). The association between extremely low
      SUA and mortality was reported in three studies; we did not perform a pooled
      analysis because of high degree of heterogeneity in these studies. CONCLUSIONS:
      Baseline SUA level is an independent predictor for future cardiovascular
      mortality. Elevated SUA appears to significantly increase the risk of all-cause
      mortality in men, but not in women. Whether low SUA levels are predictors of
      mortality is still inconclusive.

PMID- 24125413
TI  - New EAS Consensus Statement on FH: improving the care of FH patients.

PMID- 24125414
TI  - Subclinical atherosclerotic calcification and cognitive functioning in middle
      aged adults: the CARDIA study.
AB  - OBJECTIVE: Cardiovascular risk factors in middle-age are associated with
      cognitive impairment and dementia in older age. Less is known about the burden of
      calcified subclinical atherosclerosis and cognition, especially in midlife. We
      examined the association of coronary artery and abdominal aortic calcified plaque
      (CAC and AAC, respectively) with cognitive functioning in middle-aged adults.
      METHODS: This cross-sectional study included 2510 black and white adults (age: 43
      55 years) without heart disease or stroke who completed a year 25 follow-up exam
      (2010-11) as part of the Coronary Artery Risk Development in Young Adults Study.
      CAC and AAC were measured with non-contrast computed tomography. Cognition was
      assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed),
      Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT)
      (verbal memory). RESULTS: A greater amount of CAC and AAC was associated with
      worse performance on each test of cognitive function after adjustment for age,
      sex, race, education, and study center. Associations were attenuated, but
      remained significant for the DSST and RAVLT following additional adjustment for
      vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia,
      hypertension, and diabetes. Compared to participants without CAC or AAC, those
      with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST
      scores (p < 0.05). CONCLUSIONS: In this community-based sample, greater
      subclinical atherosclerotic calcification was associated with worse psychomotor
      speed and memory in midlife. These findings underscore the importance of a life
      course approach to the study of cognitive impairment with aging.

PMID- 24125415
TI  - Beetroot juice improves in overweight and slightly obese men postprandial
      endothelial function after consumption of a mixed meal.
AB  - BACKGROUND: Through effects on nitric oxide (NO) bioavailability, endothelial
      function is improved after the intake of beetroot juice-which is rich in
      inorganic nitrate-, but decreased after the intake of a meal. OBJECTIVE: The
      objective of this study was to examine if beetroot juice could counteract the
      impairment of endothelial function associated with the ingestion of a mixed meal.
      METHODS: Twenty healthy overweight and slightly obese men with a BMI between 28
      and 35 kg/m(2) received in random order a mixed meal providing 56.6 g of fat with
      beetroot juice or a control drink. The beetroot juice (140 mL) provided
      approximately 500 mg dietary nitrate. Flow-mediated dilation (FMD) of the
      brachial artery was measured before and 2 h after meal consumption. Blood was
      sampled at regular intervals. RESULTS: Postprandial changes in serum
      triacylglycerol (TAG) (P = 0.69), plasma glucose (P = 0.84) and insulin (P =
      0.67) concentrations were comparable between the meals. After consumption of
      beetroot juice, the postprandial impairment in FMD following a standardized mixed
      meal was improved (P = 0.030) compared with the control drink (-0.37 +/- 2.92%
      versus -1.56 +/- 2.90%). Following beetroot juice consumption, plasma
      concentrations of the circulating NO pool were higher at T60, T120, and T240 (P <
      0.001 at all time points). CONCLUSION: In healthy overweight and slightly obese
      men a single dose of beetroot juice attenuates the postprandial impairment of FMD
      following a mixed meal, possibly through increases in plasma NO concentrations.

PMID- 24125416
TI  - Inverse relationship between LDL cholesterol and PCSK9 plasma levels in
      dyslipidemic cynomolgus monkeys: effects of LDL lowering by ezetimibe in the
      absence of statins.
AB  - OBJECTIVES: To assess the lipid-lowering efficacy of ezetimibe in dyslipidemic
      cynomolgus monkeys comparing two dosing methods, and to evaluate PCSK9 plasma
      levels during dyslipidemia induction by feeding a high-fat/high-cholesterol diet
      (HFD), ezetimibe (Zetia((r)), Ezetrol((r))) treatment, ezetimibe washout, and HFD
      washout. METHODS AND RESULTS: Twenty dyslipidemic cynomolgus monkeys on HFD for
      seven months (LDL cholesterol 100-400 mg/dL) were randomized into two groups and
      treated with ezetimibe for two weeks, either by oral gavage or by using food
      treats. The lipid-lowering effects of ezetimibe were identical between the two
      groups. After treatment, mean LDL cholesterol was decreased by 58% (174-72
      mg/dL), total cholesterol by 42% (241-138 mg/dL), and PCSK9 levels were increased
      by 137% (147-314 ng/mL). PCSK9 levels on regular diet before and after HFD were
      also inversely correlated to LDL cholesterol. CONCLUSIONS: In a cynomolgus
      dyslipidemia model, PCSK9 levels are inversely correlated with LDL cholesterol in
      the absence of statin treatment, regardless whether lipid changes are modulated
      by diet or ezetimibe treatment.

PMID- 24125418
TI  - Peroxisome proliferator-activated receptor delta and cardiovascular disease.
AB  - Recent reports have shown that peroxisome proliferator-activated receptor delta
      (PPARD) plays an important role in different vascular processes suggesting that
      PPARD is a significant modulator of cardiovascular disease. This review will
      focus on PPARD in relation to cardiovascular risk factors based on cell, animal
      and human data. Mouse studies suggest that Ppard is an important metabolic
      modulator that may have implications for cardiovascular disease (CVD). Specific
      human PPARD gene variants show no clear association with CVD but interactions
      between variants and lifestyle factors might influence disease risk. During
      recent years, development of specific and potent PPARD agonists has also made it
      possible to study the effects of PPARD activation in humans. PPARD agonists seem
      to exert beneficial effects on dyslipidemia and insulin-resistant syndromes but
      safety issues have been raised due to the role that PPARD plays in cell
      proliferation. Thus, large long term outcome as well as detailed safety and
      tolerability studies are needed to evaluate whether PPARD agonists could be used
      to treat CVD in humans. 

PMID- 24125417
TI  - Contribution of arginase activation to vascular dysfunction in cigarette smoking.
AB  - BACKGROUND: Cigarette smoke increases the risk of several cardiovascular diseases
      and has synergistic detrimental effects when present with other risks that
      contribute to its pathogenesis. Oxidative injury to the endothelium via reactive
      oxygen species (ROS) and nitric oxide (NO) dysregulation is a common denominator
      of smoking-induced alterations in vascular function. However, the mechanisms
      underlying ROS and NO dysregulation due to smoking remain unclear. We tested if
      arginase (Arg) activation/upregulation contributes to this phenomenon by
      constraining nitric oxide synthase (NOS) activity. METHODS: Arg2 knockout (Arg2(
      /-)) and control C57BL/6J mice were either exposed to cigarette smoke, 6 h/day/2
      weeks (Second Hand Smoking; SHS) or housed in normal environment (Non Smoking;
      NS). Arg activity, NO and ROS levels were determined by measuring urea
      production, fluorescent dye (DAF), and dihydroethedium (DHE) respectively in
      isolated mouse aorta. RESULTS: Arg activity and ROS levels were higher NO lower
      in SHS compared to NS mice. SHS failed to lower NO levels in Arg2(-/-) mice.
      Endothelial dependent vasodilation (EDV) was attenuated in SHS mice as compared
      to controls (78.80% +/- 8 vs 46.58% +/- 5). This impaired EDV was abolished in
      Arg2(-/-) mice (67.48% +/- 7 in SHS vs. 78.80% +/- 8 in NS). Vascular stiffness
      was increased in SHS mice as compared to NS controls but remained unchanged in
      Arg2(-/-) mice. CONCLUSION: Endothelial NOS is uncoupled by smoking exposure,
      leading to endothelial dysfunction and vascular stiffness, a process that is
      prevented by Arg2 deletion. Hence, we identify Arg2 upregulation as a critical
      pathogenic factor and target for therapy in oxidative injury following smoking
      exposure through reciprocal regulation of endothelial NOS.

PMID- 24125419
TI  - Assessment of subclinical atherosclerosis and intraplaque neovascularization
      using quantitative contrast-enhanced ultrasound in patients with familial
      hypercholesterolemia.
AB  - OBJECTIVE: Patients with heterozygous familial hypercholesterolemia (FH) are at
      severely increased risk of developing atherosclerosis at relatively young age.
      The aim of this study was to assess the prevalence of subclinical atherosclerosis
      and intraplaque neovascularization (IPN) in patients with FH, using contrast
      enhanced ultrasound (CEUS) of the carotid arteries. METHODS: The study population
      consisted of 69 consecutive asymptomatic patients with FH (48% women, mean age 55
      +/- 8 years). All patients underwent carotid ultrasound to evaluate the presence
      and severity of carotid atherosclerosis, and CEUS to assess IPN. IPN was assessed
      in near wall plaques using a semi-quantitative grading scale and semi-automated
      quantification software. RESULTS: Carotid plaque was present in 62 patients
      (90%). A total of 49 patients had plaques that were eligible for the assessment
      of IPN: 7 patients (14%) had no IPN, 39 (80%) had mild to moderate IPN and 3 (6%)
      had severe IPN. Semi-automated quantification software showed no statistical
      significant difference in the amount of IPN between patients > 50 years and
      patients <= 50 years and between patients with a defective low-density
      lipoprotein receptor (LDLR) mutation and patients with a negative LDLR mutation.
      Plaques with irregular or ulcerated surface had significantly more IPN than
      plaques with a smooth surface (p < 0.05). CONCLUSION: Carotid ultrasound
      demonstrated atherosclerotic plaque in 90% of asymptomatic patients with FH
      without known atherosclerosis. IPN assessed with CEUS, was present in 86% of
      these patients. Irregular and ulcerated plaques exhibited significantly more IPN
      than plaques with a smooth surface.

PMID- 24125420
TI  - Fibroblast growth factor 23, left ventricular mass, and left ventricular
      hypertrophy in community-dwelling older adults.
AB  - OBJECTIVES: In chronic kidney disease (CKD), high FGF23 concentrations are
      associated with left ventricular hypertrophy (LVH), cardiovascular events, and
      death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the
      general population and the influence of CKD remains uncertain. METHODS: C
      terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by
      echocardiogram among 2255 individuals >=65 years in the Cardiovascular Health
      Study. Linear regression analysis adjusting for demographics, cardiovascular, and
      kidney related risk factors examined the associations of FGF23 concentrations
      with LVM. Analyses were stratified by CKD status and adjusted linear and logistic
      regression analysis explored the associations of FGF23 with LVM and LVH. RESULTS:
      Among the entire cohort, higher FGF23 concentrations were associated with greater
      LVM in adjusted analyses (beta = 6.71 [95% CI 4.35-9.01] g per doubling of
      FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to
      creatinine ratio >30 mg/g). Associations were stronger among participants with
      CKD (p interaction = 0.006): LVM beta = 9.71 [95% CI 5.86-13.56] g per doubling
      of FGF23 compared to those without CKD (beta = 3.44 [95% CI 0.77, 6.11] g per
      doubling of FGF23). While there was no significant interaction between FGF23 and
      CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD
      group was statistically significant and of larger magnitude than the OR for in
      the no CKD group (1.12 [95% CI 0.97-1.48]). CONCLUSION: In a large cohort of
      older community-dwelling adults, higher FGF23 concentrations were associated with
      greater LVM and LVH with stronger relationships in participants with CKD.

PMID- 24125422
TI  - Aortic arch atheroma in transient ischemic attack patients.
AB  - OBJECTIVE: Aortic arch atheroma (AAA) is associated with vascular risk factors
      and with stroke risk. Its prevalence and prognosis remain to be defined in
      patients with transient ischemic attack (TIA). METHODS: Using data from the SOS
      TIA registry, we assessed the prevalence of AAA detected by transesophageal
      echocardiography (TEE). AAA was graded as moderate (<4 mm) or severe (>=4 mm).
      All patients had a standardized work-up investigation and were followed for 1
      year. RESULTS: Between January 2003 and December 2008, 1850 patients with
      definite/possible TIA or minor stroke were enrolled and 1231 (67%) underwent TEE.
      Moderate AAA was found in 26% of patients (n = 324) and severe AAA in 14% (n =
      171), giving an overall AAA prevalence of 40%. Among the 873 patients without
      identified cause of TIA, the prevalence of moderate and severe AAA were 24% and
      12% respectively. Intracranial or extracranial stenosis >=50% were detected in
      21% of patients and were independently associated with AAA (adjusted odds ratio,
      1.65, 95% confidence interval (CI), 1.23-2.22). At one-year, incidence of
      recurrent vascular events was 2.2% in patients without AAA, 4.1% in moderate AAA
      and 6.6% in severe AAA (log-rank, p for trend = 0.003). Using patients without
      AAA as reference, and after adjustment on vascular risk factors, the hazard ratio
      (95% CI) for moderate was 1.36 (0.62-2.99) and 2.08 (0.89-4.86) for severe (p for
      trend = 0.095). CONCLUSIONS: These findings support a systematic identification
      of AAA in TIA patients to optimize risk stratification in this specific
      population.

PMID- 24125421
TI  - Genetic epidemiology and genome-wide linkage analysis of carotid artery
      ultrasound traits in multigenerational African ancestry families.
AB  - OBJECTIVE: Intima-media thickness, adventitial diameter and lumen diameter are
      indicators of cardiovascular disease risk. The influence of genetic factors on
      these measures in African ancestry populations is not well defined. Therefore, we
      estimated heritability and performed genome-wide linkage analysis of carotid
      ultrasound traits in 7 multigenerational families of African ancestry. METHODS: A
      total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative
      pairs) aged >=18 years had a common carotid artery ultrasound scan. Statistical
      analyses were conducted using pedigree-based maximum likelihood methods. RESULTS:
      Significant covariates included age, sex, body mass index or height and waist,
      and systolic blood pressure. Residual heritabilities ranged from 0.35 +/- 0.10 to
      0.64 +/- 0.12 (P < 0.0001). We identified a novel quantitative trait locus for
      adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm).
      CONCLUSION: Further fine mapping of this region may identify specific mutations
      predisposing to subclinical vascular disease among African ancestry individuals.

PMID- 24125423
TI  - Perivascular adipose tissue of the descending thoracic aorta is associated with
      systemic lupus erythematosus and vascular calcification in women.
AB  - OBJECTIVE: Women with systemic lupus erythematosus (SLE) have an increased risk
      of cardiovascular disease (CVD). Traditional CVD and SLE-disease related risk
      factors do not fully account for this increased risk. Perivascular adipose tissue
      (PVAT) is a visceral adipose depot in close proximity to blood vessels possibly
      influencing CVD. We hypothesized that women with SLE have an increased volume of
      descending thoracic aortic PVAT (aPVAT) associated with increased vascular
      calcification. METHODS: Using electron beam computed tomography, we quantified
      the aPVAT in clinically CVD-free SLE women (n = 135) and age-/race-matched
      healthy controls (HC, n = 152). Coronary artery calcification (CAC) and aortic
      calcification (AC) were quantified using Agatston scores and the aPVAT was
      quantified using standard Hounsfield Units (HU) for adipose tissue. RESULTS:
      Women with SLE had greater median aPVAT (32.2 cm(3) vs HC aPVAT 28.6 cm(3), p =
      0.0071) and greater median AC (26.0 vs HC AC 6.0, p = 0.0013) than the healthy
      control women. Total aPVAT (per 25 cm(3)) remained significantly associated with
      SLE after adjusting for CVD risk factors (Odds Ratio 1.74 [95% Confidence
      Interval: 1.04-2.9], p = 0.034), but was attenuated when adjusting for
      circulating inflammatory markers (p = 0.34). In a logistic regression analysis,
      SLE aPVAT (per 25 cm(3)) was associated with AC (6.78 [2.0-23], p = 0.0019),
      which remained significant after adjusting for circulating inflammatory markers
      (p = 0.0074), and CAC (2.66 [1.4-5.0], p = 0.0028). CONCLUSIONS: Total aPVAT is
      greater in clinically CVD-free SLE women than in age-/race-matched controls and
      is associated with calcification in different vascular beds.

PMID- 24125424
TI  - Meta-analysis identifies robust association between SNP rs17465637 in MIA3 on
      chromosome 1q41 and coronary artery disease.
AB  - Several large-scale meta-GWAS identified significant association between SNP
      rs17465637 in the MIA3 gene and coronary artery disease (CAD) in the European
      ancestry populations. However, three follow-up replication studies in the Chinese
      populations yielded inconsistent results. In order to unequivocally determine
      whether SNP rs17465637 is associated with CAD, we performed an independent case
      control association study in the Chinese Han population and a follow-up large
      scale meta-analysis for SNP rs17465637. Our study included 2503 CAD patients and
      2920 non-CAD controls of the Chinese Han origin. A significant association was
      found between SNP rs17465637 and CAD (P = 0.01, OR = 1.11). Meta-analysis
      included 7263 CAD patients and 8347 controls combined from five Asian
      populations. The association between SNP rs17465637 and CAD became highly
      significant (P = 4.97 * 10(-5), OR = 1.11). Similar analysis also identified
      significant association between SNP rs17465637 and MI (2424 cases vs.
      6,536controls; P = 5.00 * 10(-3), OR = 1.10). We conclude that SNP rs17465637 in
      MIA3 is indeed a genetic risk factor for CAD across different ethnic populations.

PMID- 24125425
TI  - A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is
      associated with chronic kidney disease.
AB  - OBJECTIVE: Studies reported a relationship between elevated asymmetric
      dimethylarginine (ADMA) concentrations and adverse renal outcomes. There is
      evidence that the rs9267551 variant in the DDAH2 gene has a functional impact
      with the C allele having a higher transcriptional activity resulting in increased
      expression of DDAH2 in endothelial cells and lower plasma ADMA levels in C allele
      carriers. METHODS: To address whether this variant is associated with chronic
      kidney disease (CDK), 2852 White European were studied. CKD was defined as
      estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). RESULTS: The
      proportion of subjects with CKD was significantly lower in C allele carriers than
      in GG genotype carriers (OR 0.49, 95%CI 0.25-0.97; P = 0.03). In a logistic
      regression model adjusted for age, gender, BMI, blood pressure, total and HDL
      cholesterol, triglyceride, and fasting plasma glucose, C allele carriers have a
      lower risk of CKD compared with GG genotype carriers (OR 0.38, 95%CI 0.18-0.78; P
      = 0.008). This association was maintained after addition to the logistic
      regression model of other confounders including glucose tolerance status,
      presence of dyslipidemia, anti-hypertensive and antidiabetic drugs (OR 0.35,
      95%CI 0.15-0.80; P = 0.01). CONCLUSION: The rs9267551 functional variant of the
      DDAH2 gene is associated with CKD with carriers of the C allele having a lower
      risk of renal dysfunction independently from several confounders. Because ADMA
      predicted progression of renal disease, it is possible that, in GG carriers, ADMA
      may accumulate at the renal level causing endothelial dysfunction as a
      consequence of reduced nitric oxide availability and potentiating micro-vascular
      damage.

PMID- 24125426
TI  - The impact of serum uric acid level on arterial stiffness and carotid
      atherosclerosis: the Korean Multi-Rural Communities Cohort study.
AB  - OBJECTIVE: Serum uric acid level has been found to be associated with a risk
      factor for cardiovascular diseases. However, the topic has not been explored in
      the general population, especially in Korea. This study was designed to determine
      whether serum uric acid is associated with carotid atherosclerosis and arterial
      stiffness in the Korean Multi-Rural Communities Cohort study. METHODS: A total of
      5568 participants from the Korean Multi-Rural Communities Cohort were evaluated
      for the risk of hyperuricemia in cardiovascular atherosclerosis. Important
      surrogates for cardiovascular atherosclerosis such as intima-media thickness
      (IMT) and brachial-ankle pulse wave velocity (baPWV) were assessed. We evaluated
      the association between these atherosclerosis indices and serum uric acid level
      or hyperuricemia through multivariate-adjusted logistic and linear regression
      analyses. RESULTS: There was a significant difference of carotid IMT and baPWV
      between males and females (p < 0.0001, respectively). Both male and female
      subjects with hyperuricemia showed higher baPWV than subjects without
      hyperuricemia (p = 0.0004 for males; p = 0.001 for females). Serum uric acid
      level was positively correlated with baPWV in males (beta = 0.0006, p < 0.0001)
      and in females (beta = 0.0001, p = 0.04), whereas no association between serum
      uric acid and carotid IMT was found in either gender. A linear relationship of
      baPWV with increasing serum uric acid level was observed in males (p = 0.0005)
      and in females (p = 0.004). CONCLUSION: Serum uric acid level could be considered
      an important risk factor for arterial stiffness in Korean population, whereas
      carotid IMT is not associated with serum uric acid in either gender when using
      data from the Korean Multi-Rural Communities Cohort study.

PMID- 24125427
TI  - Prevalence and determinants of metabolically healthy obesity in Spain.
AB  - BACKGROUND AND AIMS: Obesity is a heterogeneous disorder, so some obese
      individuals do not have cardiometabolic abnormalities (CA) which mediate the
      association between obesity and coronary heart disease. This study assessed the
      prevalence of metabolically healthy obesity and its determinants in Spain.
      METHODS: The data were taken from a cross-sectional study conducted in 2008-2010
      among 11,520 individuals representative of the population of Spain aged >=18
      years. Normal-weight was defined as body mass index (BMI) <25 kg/m(2), and
      obesity as BMI >=30 kg/m(2). Six CA were considered: elevated blood pressure, low
      high-density lipoprotein cholesterol, and elevated levels of triglycerides,
      fasting glucose, homeostasis model assessment of insulin resistance value, and C
      reactive protein. Then, two phenotypes were defined: healthy (0-1 CA) and
      abnormal (>=2 CA). RESULTS: The prevalence of metabolically healthy obesity was
      6.5% overall (95% confidence interval: 6.0-7.1), and corresponds to 28.9% of
      obese individuals. Lower age, being female, current smoking, moderate alcohol
      consumption, and high level of physical activity were independently associated
      with the healthy phenotype among the obese. The prevalence of normal weight with
      a metabolically abnormal phenotype was 6.4% overall (95% confidence interval: 5.8
      6.9) and corresponds to 16.8% of normal-weight subjects. Factors associated with
      this phenotype in normal-weight persons were higher age, being male, never
      smoking, no alcohol consumption and larger waist circumference. CONCLUSION:
      Metabolically healthy obesity represents almost one-third of the obese population
      in Spain. Since this was a cross-sectional study, the association of metabolic
      healthy obesity with smoking consumption, alcohol intake and physical activity
      warrants more research.

PMID- 24125428
TI  - A gene variant in the Atp10d gene associates with atherosclerotic indices in
      Japanese elderly population.
AB  - BACKGROUND: ATP10D belongs to a subfamily of P-type ATPases implicated in
      phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of
      cellular biological membrane. Previous genome-wide association study (GWAS)
      identified that a variant in Atp10d gene (rs2351791) associates with serum lipid
      profile and myocardial infarction. The objective of this study is to assess the
      effect of this variant on atherosclerosis in Japanese elderly population. METHOD:
      Consecutive autopsy cases registered in JG-SNP study were recruited (n = 1536).
      The samples were pathologically assessed for atherosclerosis using macroscopic
      examination of the formalin-fixed arteries, and coronary stenotic index (CSI),
      intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index
      (PAI), which represent systemic arteries were calculated. The variant rs2351791
      (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association
      determined. RESULT: Both CSI and ICAI were significantly higher in GG genotype
      than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both
      associations remained significant in minor allele dominant model after adjusting
      for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p =
      0.001, respectively). PAI was not associated with this variant. Consistent with
      the previous report, plasma HDL cholesterol level was lower in GG genotype
      compared to GT + TT genotypes (p = 0.001). CONCLUSION: The rs2351791 SNP in the
      Atp10d gene affects the susceptibility for cardiac and intracranial vascular
      stenosis in the elderly Japanese population.

PMID- 24125431
TI  - Alkahest for V2VI3 chalcogenides: dissolution of nine bulk semiconductors in a
      diamine-dithiol solvent mixture.
AB  - The ability to solution deposit semiconductor films has received a great deal of
      recent attention as a way to potentially lower costs for many optoelectronic
      applications; however, most bulk semiconductors are insoluble in common solvents.
      Here we describe a novel and relatively nonhazardous binary solvent mixture
      comprised of 1,2-ethanedithiol and 1,2-ethylenediamine that possesses the
      remarkable ability to rapidly dissolve a series of nine bulk V2VI3 chalcogenides
      (V = As, Sb, Bi; VI = S, Se, Te) at room temperature and atmospheric pressure.
      After solution deposition and low-temperature annealing, the chalcogenides can be
      fully recovered as good quality, highly crystalline thin films with negligible
      organic content, as demonstrated for Sb2Se3 and Bi2S3. 

PMID- 24125430
TI  - Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte
      telomere length in atherosclerosis.
AB  - AIMS: Leukocyte telomere length (LTL) is shortened in patients with clinical
      atherosclerosis (AS). Here we aimed to explore the contribution of elevated
      homocysteine (Hcy) level to LTL shortening in AS patients and the underlying
      mechanism. METHODS: Circulating leukocytes were collected from 197 patients with
      AS and 165 sex- and age-matched healthy subjects for LTL determination. mRNA
      expression or DNA methylation of human telomerase reverse transcriptase (hTERT)
      was determined by real-time PCR and methylation-specific PCR assay, respectively.
      We established a hyperhomocysteinemia (HHcy) mice model to confirm human results.
      RESULTS: Hcy was negatively correlated with LTL shortening in AS patients (r = 
      0.179, p = 0.015) and controls (r = -0.146, p = 0.031). Serum folate and high
      sensitivity C-reactive protein levels significantly interacted with Hcy in LTL
      shortening. Hcy was related to hTERT mRNA downregulation and promoter
      demethylation, which combined was associated with LTL shortening in AS patients.
      Hcy-induced LTL shortening did not differ by sites of AS lesions or infarction.
      Similar to clinical observations, our HHcy mice model suggested that Hcy induced
      DNA demethylation and downregulation of mouse TERT and further contributed to LTL
      shortening. CONCLUSIONS: Elevated Hcy level induced DNA demethylation of hTERT
      and was closely related with hTERT downregulation, which led to LTL shortening in
      AS. These findings provide novel insights into an epigenetic mechanism for Hcy
      related AS.

PMID- 24125429
TI  - Cardiovascular risk in rheumatoid arthritis: how to lower the risk?
AB  - Patients with rheumatoid arthritis (RA) carry an excess risk for cardiovascular
      disease, which is comparable to the risk in patients with type 2 diabetes
      mellitus. The mechanisms involved are partly related to traditional
      cardiovascular risk factors, disease-associated inflammation and undertreatment
      of traditional cardiovascular disease (CVD) risk factors. Since atherosclerosis
      is an inflammatory disease, the auto-immune mediated inflammation observed in RA
      patients contributes to increased endothelial dysfunction, oxidative stress and
      activation and vascular migration of leukocytes. This concept is underscored by
      the CVD risk reduction that is seen by anti-inflammatory disease modifying anti
      rheumatic drugs such as methotrexate and TNFalpha inhibitors. The evidence for
      underdiagnosis and undertreatment of traditional CVD risk factors in RA
      strengthens the potential benefit of structured CVD risk management in these
      patients. Current cardiovascular guidelines recommend screening and treatment of
      CVD risk factors in RA patients, without well defined treatment targets. At
      present, there is a lack of scientific evidence to establish treatment targets
      for CVD risk factors in RA. Therefore, expanding research regarding screening and
      treatment of traditional CVD risk factors in RA patients is needed. 

PMID- 24125432
TI  - Single arc volumetric-modulated arc therapy is sufficient for nasopharyngeal
      carcinoma: a dosimetric comparison with dual arc VMAT and dynamic MLC and step
      and-shoot intensity-modulated radiotherapy.
AB  - BACKGROUND: The performance of single arc VMAT (VMAT1) for nasopharyngeal
      carcinoma (NPC) on the Axesse linac has not been well described in previous
      studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC
      by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT
      (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot
      intensity-modulated radiotherapy (ssIMRT). METHODS: Twenty consecutive patients
      with non-metastatic NPC were selected to be planned with VMAT1, VMAT2, dIMRT and
      ssIMRT using Monaco 3.2 TPS on the AxesseTM linear accelerator. Three planning
      target volumes (PTVs), contoured as high risk, moderate risk and low risk
      regions, were set to receive median absorbed-dose (D50%) of 72.6 Gy, 63.6 Gy and
      54 Gy, respectively. The Homogeneity Index (HI), Conformity Index (CI), Dose
      Volume Histograms (DVHs), delivery efficiency and accuracy were all evaluated.
      RESULTS: Mean HI of PTV72.6 is better with VMAT1(0.07) and VMAT2(0.07) than
      dIMRT(0.09) and ssIMRT(0.09). Mean HI of PTV63.6 is better with VMAT1(0.21) and
      VMAT2(0.21) than dIMRT and ssIMRT. Mean CI of PTV72.6 is also better with
      VMAT1(0.57) and VMAT2(0.57) than dIMRT(0.49) and ssIMRT(0.5). Mean CI of PTV63.6
      is better with VMAT1(0.76) and VMAT2(0.76) than dIMRT(0.73) and ssIMRT(0.73).
      VMAT had significantly improved homogeneity and conformity compared with IMRT.
      There was no significant difference between VMAT1 and VMAT2 in PTV coverage. Dose
      to normal tissues was acceptable for all four plan groups. VMAT1 and VMAT2 showed
      no significant difference in normal tissue sparring, whereas the mean dose of the
      parotid gland of dIMRT was significantly reduced compared to VMAT1 and VMAT2. The
      mean delivery time for VMAT1, VMAT2, dIMRT and ssIMRT was 2.7 min, 3.9 min, 5.7
      min and 14.1 min, respectively. VMAT1 reduced the average delivery time by 29.8%,
      51.1% and 80.8% compared with VMAT2, dIMRT and ssIMRT, respectively. VMAT and
      IMRT could all be delivered accurately based on our quality assurance standards.
      CONCLUSIONS: In the treatment of NPC using the AxesseTM linear accelerator,
      single arc VMAT has shown superiority to double arc VMAT, dIMRT and ssIMRT in
      delivery efficiency, without compromise to the PTV coverage. However, there is
      still room for improvement in terms of OAR sparing.

PMID- 24125433
TI  - Multiplexed detection of DNA sequences using a competitive displacement assay in
      a microfluidic SERRS-based device.
AB  - We demonstrate sensitive and multiplexed detection of DNA sequences through a
      surface enhanced resonance Raman spectroscopy (SERRS)-based competitive
      displacement assay in an integrated microsystem. The use of the competitive
      displacement scheme, in which the target DNA sequence displaces a Raman-labeled
      reporter sequence that has lower affinity for the immobilized probe, enables
      detection of unlabeled target DNA sequences with a simple single-step procedure.
      In our implementation, the displacement reaction occurs in a microporous packed
      column of silica beads prefunctionalized with probe-reporter pairs. The use of a
      functionalized packed-bead column in a microfluidic channel provides two major
      advantages: (i) immobilization surface chemistry can be performed as a batch
      process instead of on a chip-by-chip basis, and (ii) the microporous network
      eliminates the diffusion limitations of a typical biological assay, which
      increases the sensitivity. Packed silica beads are also leveraged to improve the
      SERRS detection of the Raman-labeled reporter. Following displacement, the
      reporter adsorbs onto aggregated silver nanoparticles in a microfluidic mixer;
      the nanoparticle-reporter conjugates are then trapped and concentrated in the
      silica bead matrix, which leads to a significant increase in plasmonic
      nanoparticles and adsorbed Raman reporters within the detection volume as
      compared to an open microfluidic channel. The experimental results reported here
      demonstrate detection down to 100 pM of the target DNA sequence, and the
      experiments are shown to be specific, repeatable, and quantitative. Furthermore,
      we illustrate the advantage of using SERRS by demonstrating multiplexed
      detection. The sensitivity of the assay, combined with the advantages of
      multiplexed detection and single-step operation with unlabeled target sequences
      makes this method attractive for practical applications. Importantly, while we
      illustrate DNA sequence detection, the SERRS-based competitive displacement assay
      is applicable to detection of a variety of biological macromolecules, including
      proteins and proteolytic enzymes. 

PMID- 24125434
TI  - Genotyping of Giardia isolates in Scotland: a descriptive epidemiological study.
AB  - Giardiasis, caused by the intestinal protozoan parasite Giardia intestinalis
      (synonyms: G. lamblia, G. duodenalis), is one of the most frequent parasites to
      infect the Scottish population. Transmission of the infective cysts in faecal
      matter is commonly via food and/or water. Giardia is subdivided into assemblages,
      where clinical and epidemiological differences have been described between
      assemblages A and B. This snapshot descriptive epidemiological study examines 30
      positive cases of Giardia of which 72% (n = 21) were shown to be assemblage A,
      14% (n = 4) assemblage B and 10% (n = 3) mixed assemblages (A and B). There was a
      2:3 female:male ratio of affected individuals with foreign travel recorded in 22
      of these cases. The commonest symptom was diarrhoea which was reported in 80% of
      cases followed by tiredness. Five cases required hospitalization emphasizing the
      importance of gaining a greater understanding of how Giardia assemblages
      influence clinical outcomes to assist in formulating guidelines to manage
      potential Giardia outbreaks.

PMID- 24125435
TI  - Pneumonia: a disease for all ages.

PMID- 24125436
TI  - Smoking and tuberculous infection: chasing associations with imperfect exposure
      and outcome measures.

PMID- 24125437
TI  - TIMEBOMB revisited 10 years later: can we sustain progress or are we losing the
      war?
AB  - TIMEBOMB: The Global Epidemic of Multidrug-Resistant Tuberculosis was published
      in September 2001 to call attention to a deteriorating global tuberculosis (TB)
      situation. Although its impact was blunted by the events of 11 September, it is
      sobering to compare its description of TB problems at that time with the state of
      global TB control at present. TB--and the even worse resistant forms of the
      disease, multi-, extensively and even totally drug-resistant TB, a problem
      completely of our own making-is out of control due to neglect and inattention.
      Urgent attention is required to begin to rectify the situation.

PMID- 24125438
TI  - Role of the QuantiFERON(r)-TB Gold In-Tube test in the diagnosis of intrathoracic
      childhood tuberculosis.
AB  - SETTING: Tertiary care hospitals in India. OBJECTIVE: To compare the performance
      of the QuantiFERON(r)-TB Gold In-Tube test (QFT-GIT) with that of the tuberculin
      skin test (TST) in the diagnosis of intrathoracic childhood tuberculosis (TB).
      METHODS: Children with intrathoracic TB were enrolled in a randomised controlled
      trial studying micronutrient supplementation in intrathoracic TB. They underwent
      TST and QFT-GIT before starting daily anti-tuberculosis treatment. RESULTS: Of
      362 children (median age 115.5 months, IQR 73-144, 55% girls) enrolled in the
      study, microbiological confirmation of TB was obtained in 128 (35%). The TST was
      positive in 337 (93%, 95%CI 90-95.5) and QFT-GIT in 297 (82%, 95%CI 77.8-85.6).
      Sensitivity of TST and QFT-GIT in culture-confirmed TB cases was respectively
      90.5% (95%CI 84.1-94.5) and 82.6% (95%CI 74.9-88.4). QFT-GIT positivity rate
      correlated with TST induration (P < 0.001). TST was influenced by the disease
      spectrum (P = 0.004) and the age of the children (P = 0.002); QFT-GIT remained
      unaffected by these factors. Bacille Calmette-Guerin immunisation status, weight
      for-age Z-scores and microbiological confirmation of Mycobacterium tuberculosis
      did not influence the performance of either test. CONCLUSION: In high-burden
      countries, QFT-GIT is comparable to TST and offers no added advantage in the
      diagnosis of childhood intrathoracic TB.

PMID- 24125439
TI  - Risk factors for mortality in Malawian children with human immunodeficiency virus
      and tuberculosis co-infection.
AB  - SETTING: A large urban pediatric human immunodeficiency virus (HIV) clinic in
      Lilongwe, Malawi. OBJECTIVE: To identify demographic and clinical risk factors
      for mortality in children co-infected with HIV and tuberculosis (TB). DESIGN: A
      retrospective cohort study of HIV-infected children (aged <18 years) enrolled
      between October 2004 and October 2010 with at least one current or historical TB
      diagnosis. Descriptive statistics and logistic regression analyses were performed
      to determine factors associated with mortality. RESULTS: A total of 1561 patients
      met the inclusion criteria, representing 32% of patients ever enrolled. Median
      age at TB diagnosis was 3.8 years (interquartile range 1.5-7.4); 60.9% had severe
      immune suppression and 47.6% of those with available data had some degree of
      acute malnutrition at TB diagnosis. Of the 1113 patients with known outcomes, 225
      (20.2%) died. Children with TB-HIV co-infection not initiated on antiretroviral
      therapy (ART) at any time were 8.8 times more likely to die compared to those
      initiated on ART 0-2 months after initiation of anti-tuberculosis treatment
      (adjusted OR 8.83, 95%CI 4.42-17.63). Severe immunosuppression and World Health
      Organization Stage IV were also associated with mortality. CONCLUSIONS: Pediatric
      TB-HIV co-infection is common and mortality is high in this cohort of Malawian
      children. Prompt initiation of ART should be emphasized in this high-risk patient
      population.

PMID- 24125440
TI  - Improving tuberculosis screening and isoniazid preventive therapy in an HIV
      clinic in Addis Ababa, Ethiopia.
AB  - BACKGROUND: The World Health Organization (WHO) recommends active tuberculosis
      (TB) case finding among people living with human immunodeficiency virus (HIV) in
      resource-limited settings using a symptom-based algorithm; those without active
      TB disease should be offered isoniazid preventive therapy (IPT). OBJECTIVE: To
      evaluate rates of adherence to WHO recommendations and the impact of a quality
      improvement intervention in an HIV clinic in Addis Ababa, Ethiopia. DESIGN: A
      prospective study design was utilized to compare TB symptom screening and IPT
      administration rates before and after a quality improvement intervention
      consisting of 1) educational sessions, 2) visual reminders, and 3) use of a
      screening checklist. RESULTS: A total of 751 HIV-infected patient visits were
      evaluated. The proportion of patients screened for TB symptoms increased from 22%
      at baseline to 94% following the intervention (P < 0.001). Screening rates
      improved from 51% to 81% (P < 0.001) for physicians and from 3% to 100% (P <
      0.001) for nurses. Of the 281 patients with negative TB symptom screens and
      eligible for IPT, 4% were prescribed IPT before the intervention compared to 81%
      after (P < 0.001). CONCLUSIONS: We found that a quality improvement intervention
      significantly increased WHO-recommended TB screening rates and IPT
      administration. Utilizing nurses can help increase TB screening and IPT provision
      in resource-limited settings.

PMID- 24125442
TI  - Results of rapid and successful integration of HIV diagnosis and care into
      tuberculosis services in Benin.
AB  - SETTING: Benin, where 20 of 54 tuberculosis (TB) clinics caring for 80% of all TB
      patients began providing integrated human immunodeficiency virus (HIV) care in
      2005. OBJECTIVE: To describe the characteristics and TB treatment outcomes of the
      first cohorts of TB-HIV patients, and to assess programmatic outcomes. METHODS:
      Retrospective cohort study using data from the TB register and the register of co
      infected patients. RESULTS: During the study period, 8368 TB patients were
      registered, 7787 (93%) were tested for HIV and 1255 (16%) were HIV-positive,
      including 385 (32%) who already knew their positive status. Most patients (88%)
      were tested within 15 days of TB diagnosis. Female and young patients were
      overrepresented among the co-infected. Cotrimoxazole preventive therapy was
      administered to 1152 patients (95%) during anti-tuberculosis treatment, and
      antiretroviral treatment (ART) to 469 (42%). The likelihood of receiving ART
      increased as initial CD4 lymphocyte counts decreased. Fifteen per cent of TB-HIV
      patients died during anti-tuberculosis treatment. Patients already on ART prior
      to anti-tuberculosis treatment experienced the worst outcomes. Patients who
      initiated ART early during anti-tuberculosis treatment or in the timeframe
      recommended by the guidelines fared the best. CONCLUSION: HIV care has been
      successfully and sustainably integrated into TB services in Benin. However,
      ensuring the access of co-infected patients to more favourable treatment outcomes
      still represents significant challenges.

PMID- 24125441
TI  - Integrating HIV testing and care into tuberculosis services in Benin:
      programmatic aspects.
AB  - SETTING: Between 2005 and 2008, the diagnosis and care of human immunodeficiency
      virus (HIV) infection and tuberculosis (TB) services were integrated in Benin.
      RESULTS: The appointment of a TB-HIV Coordinator by the National Tuberculosis
      Control Programme and quarterly supervisory visits to TB clinics have bolstered
      the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole
      preventive therapy were integrated smoothly into the TB services. The strategy
      chosen to facilitate access of HIV-positive TB patients to antiretroviral
      treatment contributed to greater integration over time, but perpetuated, for
      some, the burden of attending two facilities. CONCLUSION: The integration and
      decentralisation of TB and HIV care services at national level in Benin resulted
      in a high uptake of HIV services among TB patients.

PMID- 24125443
TI  - Impact of HIV on clinical presentation and outcomes of tuberculosis treatment at
      primary care level.
AB  - Little is known on how human immunodeficiency virus (HIV) infection impacts
      pediatric tuberculosis (TB) in primary care. We compared TB type, HIV care and
      case fatality rates between 5685 adults and 830 children with TB treated at
      primary care clinics in Kinshasa, Democratic Republic of Congo. Children
      represented a substantial burden (13%) of TB, and presented predominantly with
      difficult to diagnose smear-negative TB and extra-pulmonary TB. The HIV co
      infection rate was lower in children than in adults, and fewer children than
      adults received antiretroviral therapy during anti-tuberculosis treatment. Case
      fatality was four times higher in HIV-infected than non-infected children. Child
      friendly point-of-care TB diagnostics and decentralized pediatric TB-HIV care
      should receive greater attention. 

PMID- 24125444
TI  - Tuberculosis among the homeless, United States, 1994-2010.
AB  - OBJECTIVES: 1) To describe homeless persons diagnosed with tuberculosis (TB)
      during the period 1994-2010, and 2) to estimate a TB incidence rate among
      homeless persons in the United States. METHODS: TB cases reported to the National
      Tuberculosis Surveillance System were analyzed by origin of birth. Incidence
      rates were calculated using the US Department of Housing and Urban Development
      homeless population estimates. Analysis of genotyping results identified
      clustering as a marker for transmission among homeless TB patients. RESULTS: Of
      270,948 reported TB cases, 16,527 (6%) were homeless. The TB incidence rate among
      homeless persons ranged from 36 to 47 cases per 100,000 population in 2006-2010.
      Homeless TB patients had over twice the odds of not completing treatment and of
      belonging to a genotype cluster. US- and foreign-born homeless TB patients had
      respectively 8 and 12 times the odds of substance abuse. CONCLUSIONS: Compared to
      the general population, homeless persons had an approximately 10-fold increase in
      TB incidence, were less likely to complete treatment and more likely to abuse
      substances. Public health outreach should target homeless populations to reduce
      the excess burden of TB in this population.

PMID- 24125445
TI  - Risk factors for death among hospitalised tuberculosis patients in poor urban
      areas in Manila, The Philippines.
AB  - OBJECTIVE: To determine the mortality rate and risk factors for in-hospital death
      among hospitalised human immunodeficiency virus (HIV) negative tuberculosis (TB)
      patients in poor urban areas in the Philippines. DESIGN: A cross-sectional study
      was conducted at a national infectious disease hospital in Manila City. The
      target population was patients aged >= 13 years with all forms of HIV-negative TB
      admitted from October to December 2009. Demographic and clinical information was
      collected from medical charts, and risk of in-hospital death was measured.
      RESULTS: Of 407 HIV-negative TB patients, four were excluded due to missing
      records, and 403 were included in the analysis. The majority were poor urban
      residents (90%), and 66% were males. Overall, 37.5% of hospitalised patients died
      in the hospital (151/403), 30% of whom died before the third day of
      hospitalisation. Risk factor analysis demonstrated that complications of
      bacterial pneumonia had the greatest effect on in-hospital death (aOR 4.53, 95%CI
      2.65-7.72), followed by anorexia (aOR 3.01, 95%CI 1.55-5.84), anaemia
      (haemoglobin <10 g/dl, aOR 2.35, 95%CI 1.34-4.13) and older age (aged >= 50
      years, aOR 1.85, 95%CI 1.08-3.17). The presence of haemoptysis (aOR 0.44, 95%CI
      0.25-0.80) was associated with improved survival. CONCLUSION: Mortality among
      hospitalised HIV-negative TB patients was extremely high in poor urban areas in
      the Philippines.

PMID- 24125446
TI  - Treatment outcomes of tuberculosis patients in Brazilian prisons: a polytomous
      regression analysis.
AB  - SETTING: Tuberculosis (TB) is a major public health problem and an important
      cause of infectious disease-related death in young adults. TB rates are higher in
      vulnerable populations, including prisoners. OBJECTIVE: To describe the clinical
      and epidemiological characteristics associated with anti-tuberculosis treatment
      outcomes in the Brazilian prison population. DESIGN: The study population
      consisted of prisoners diagnosed with TB identified through the Sistema de
      Informacao de Agravos de Notificacao (Information System for Notifiable Diseases)
      between January 2007 and December 2011. Pearson's chi(2) test was used to compare
      the proportions and covariates associated with the outcome of interest. These
      variables were further analysed using the polytomous regression model. RESULTS:
      Compared to those who completed anti-tuberculosis treatment, prisoners who
      defaulted from treatment were younger (P < 0.001), less educated (P < 0.001) and
      more likely to be alcoholic (P < 0.001); they were more likely to have recurrent
      or relapse TB (P < 0.001) and they were not under directly observed treatment (P
      < 0.001). Those who died from TB tended to be older (P < 0.001) and alcoholic (P
      < 0.001); they were also more likely to have received treatment of unknown type
      (P < 0.001) and to have both pulmonary and extra-pulmonary TB (EPTB). Prisoners
      who developed multidrug-resistant TB were more likely to experience TB
      recurrence, return to treatment after default, change treatment centres and have
      EPTB. CONCLUSION: Our results highlight the need to improve TB control and
      policies in correctional facilities. Improving treatment outcomes of prisoners
      will also prevent transmission to other prisoners, their family members, and
      health professionals.

PMID- 24125447
TI  - Monitoring changes in anti-tuberculosis treatment: associated factors determined
      at the time of diagnosis.
AB  - OBJECTIVES: To determine predictive factors for changes in standard anti
      tuberculosis chemotherapy at the time of diagnosis. METHODS: A prospective study
      was performed among tuberculosis (TB) patients treated at specialised centres
      during 2008-2009. Treatment outcome was monitored per standard guidelines.
      Treatment was considered successful if the patient was cured or completed
      treatment. Factors associated with treatment modification were analysed at the
      bivariate and multivariate levels using logistic regression. RESULTS: A total of
      427 patients were included in the study. The initial standard treatment regimen
      was retained for 249 patients (58.3%), extended to 9 months for 36 (8.4%) and
      changed for 142 (33.3%). Factors associated with a change of regimen at the
      multivariate level were female sex, age >= 50 years, human immunodeficiency virus
      infection, comorbidities, alcoholism, hospitalisation and culture-positive
      sputum. Drug resistance and toxicity were analysed independently. Treatment
      outcome was successful in 97.2% of cases without a regimen change and in 87.3% of
      those with a changed regimen (P < 0.001). CONCLUSION: Factors associated with
      changes in the initial anti-tuberculosis regimen should be considered for
      rigorous follow-up. Results obtained through individualised treatment provided by
      specialists were good despite the complexity of the cases treated.

PMID- 24125448
TI  - Pharmacokinetics and serum concentrations of antimycobacterial drugs in adult
      Turkish patients.
AB  - OBJECTIVE: To document the pharmacokinetics and serum concentrations of first
      line anti-tuberculosis drugs in adult Turkish patients with pulmonary
      tuberculosis (PTB). DESIGN: Consenting 21 adult patients (aged 38 +/- 4 years, 10
      female and 11 male) with newly diagnosed active PTB participated in the study.
      Blood samples were collected 1, 2, 4, 6 and 24 h after simultaneous isoniazid
      (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB) ingestion. Serum
      concentration-time profiles, maximum serum concentrations, time to achieve
      maximum serum concentrations, the half-life and the areas under the serum
      concentration-time curve for each of the four drugs were determined. RESULTS:
      Wide variations in pharmacokinetic parameters were observed among patients. In
      respectively 8 (38%), 17 (81%), 3 (14%) and 1 (5%) patients, the maximum INH,
      RMP, PZA and EMB serum concentrations were below the accepted therapeutic
      concentrations. CONCLUSION: Our data show that the serum concentrations of anti
      tuberculosis drugs varied considerably in the study patients. Therapeutic drug
      monitoring is necessary to identify patients with subtherapeutic INH and RMP
      serum concentrations.

PMID- 24125449
TI  - Comparison of time to positive and colony counting in an early bactericidal
      activity study of anti-tuberculosis treatment.
AB  - SETTING: Patients with smear-positive, newly diagnosed pulmonary tuberculosis
      (TB) presenting to the out-patient TB clinic in Kampala, Uganda. OBJECTIVE: To
      compare colony-forming unit (cfu) counting and time to positive (TTP) in
      Mycobacteria Growth Indicator Tube (MGIT) culture as measures of early
      bactericidal activity (EBA). DESIGN: Patients were enrolled in an EBA feasibility
      study of standard TB chemotherapy. Sixteen-hour overnight sputum collections were
      obtained before and on days 2, 4, 7, 10, 12 and 14 of treatment for quantitative
      culture on selective Middlebrook 7H11 agar media and TTP in the MGIT liquid
      culture system. RESULTS: Log cfu and TTP were correlated over all time points
      (r(s) = -0.71, P < 0.001). Within-subject (day to day) variation as a percentage
      of total variation was very similar between the two measures: 25.7% for cfu and
      25% for TTP. Mean EBA 0-14, 0-2 and 2-14 measured by TTP were similar to those
      previously reported. CONCLUSION: TTP measured by an automated, standardized,
      commercially available culture system correlates with cfu determinations. EBA
      measured by TTP provides similar information to cfu counting, and is reproducible
      across sites and in different patient populations. These findings support
      replacing cfu counting with TTP as the primary measurement in EBA studies.

PMID- 24125451
TI  - Comparison of molecular and immunological methods for the rapid diagnosis of
      smear-negative tuberculosis.
AB  - SETTING: The rapid diagnosis of pulmonary tuberculosis (TB) can be challenging if
      acid-fast bacilli are not detected by sputum smear microscopy. OBJECTIVE: To
      compare the results of the GeneXpert(r) MTB/RIF assay on a single sputum or
      bronchoalveolar lavage (BAL) specimen test with local immunodiagnosis from the
      site of disease using the T-SPOT(r).TB assay on BAL (BAL T-SPOT). DESIGN: The
      Xpert and BAL T-SPOT tests were compared in 96 patients suspected of having
      sputum smear-negative pulmonary TB admitted to a referral centre in Germany.
      RESULTS: BAL T-SPOT identified 10 of 11 patients with pulmonary TB (including 3/4
      patients with culture-confirmed TB) with a negative Xpert test. Using Xpert, the
      sensitivity, specificity and positive and negative likelihood ratios (LRs) were
      respectively 60.0%, 97.4%, 30.0% and 0.4% in culture-confirmed cases and 42.1%,
      97.4%, 21.1% and 0.6% in all TB patients. In contrast, using BAL T-SPOT, the
      sensitivity, specificity and positive and negative LRs were respectively 80.0%,
      62.6%, 2.1% and 0.3% in culture-confirmed cases and 89.4%, 62.6%, 2.4% and 0.2%
      in all TB patients. CONCLUSION: In sputum smear-negative TB suspects, a positive
      Xpert result is strongly indicative of culture confirmation; however, a negative
      result is insufficient to rule out active TB. Where clinical suspicion of
      pulmonary TB persists despite a negative Xpert result, local immunodiagnosis
      using T-SPOT on BAL may increase diagnostic accuracy.

PMID- 24125452
TI  - Similar seasonal peak in clustered and unique extra-pulmonary tuberculosis
      notifications: winter crowding hypothesis ruled out?
AB  - BACKGROUND: The incidence of extra-pulmonary tuberculosis (EPTB) in the
      Netherlands shows a seasonal trend, with a peak in spring and a trough in autumn.
      Possible causes of this peak are winter crowding and a seasonal decrease in
      immune competence in spring. A third explanation may be a reporting bias.
      OBJECTIVE: To investigate the role of winter crowding by a time-series analysis
      of notification data. DNA fingerprinting clustering status can differentiate
      between recent and remote infections. Seasonality in clustered cases would
      reflect enhanced transmission in winter and/or seasonally lowered immunity, while
      seasonality in unique cases would only reflect seasonally lowered immunity.
      METHODS: We fitted (seasonal) auto-regressive moving average models to culture
      positive TB notifications in the Netherlands (1993-2008) to assess seasonality.
      We then used seasonal trend Loess decompositions to derive the seasonal pattern,
      and compared the heights of the seasonal peaks. RESULTS: Clustered and unique
      EPTB notifications showed a seasonal trend that was absent in clustered and
      unique PTB notifications. The seasonal peak in clustered EPTB cases was not
      significantly higher than in unique EPTB cases. CONCLUSIONS: The similar timing
      and height of the seasonal peak of clustered and unique EPTB cases suggests that
      winter crowding is unlikely to cause the seasonal trend in notifications.

PMID- 24125450
TI  - Dose-response association between salivary cotinine levels and Mycobacterium
      tuberculosis infection.
AB  - SETTING: Tijuana, Mexico. OBJECTIVE: To describe the association between salivary
      cotinine levels and interferon-gamma (IFN-gamma) release assay results. DESIGN:
      We conducted a cross-sectional study among injection drug users. Salivary
      cotinine levels were measured using NicAlert, a semi-quantitative dipstick assay.
      QuantiFERON(c)-TB Gold In-Tube (QFT-GIT) was used to determine Mycobacterium
      tuberculosis infection. RESULTS: Among 234 participants, the prevalence of QFT
      GIT positivity for NicAlert cotinine categories 0 (non-smoking), 1 (second-hand
      smoke exposure or low-level smoking) and 26 (regular smoking) were respectively
      42.1%, 46.4% and 65.2% (Ptrend 0.012). We found increasing trends in QFT-GIT
      positivity (Ptrend 0.003) and IFN-gamma concentrations (Spearman's r 0.200, P
      0.002) across cotinine levels 0 to 6. In multivariable log-binomial regression
      models adjusted for education, cotinine levels were not associated with QFT-GIT
      positivity when included as smoking categories (1 and 26 vs. 0), but were
      independently associated with QFT-GIT positivity when included as an ordinal
      variable (prevalence ratio 1.09 per 1 cotinine level, 95%CI 1.021.16).
      CONCLUSION: Our findings suggest that a dose-response relationship exists between
      tobacco smoke exposure and M. tuberculosis infection. Longitudinal studies that
      use biochemical measures for smoking status are needed to confirm our findings.

PMID- 24125453
TI  - Contribution of CD14-159C/T polymorphism to tuberculosis susceptibility: a meta
      analysis.
AB  - BACKGROUND: CD14 plays an important role in recognising the tuberculosis (TB)
      antigen and initiating immune response. CD14-159C/T polymorphism has been
      reported to be associated with susceptibility to TB in some, but not all studies.
      OBJECTIVE: To comprehensively evaluate the correlation between CD14-159C/T
      polymorphism and susceptibility to TB. METHODS: Relevant studies from six English
      language databases were searched up to 15 March 2013. Crude odd ratios (ORs) with
      95% confidence interval (CIs) were calculated to assess the strength of
      associations. RESULTS: Eight eligible studies including 3583 subjects were
      retained for the meta-analysis. T-allele and TT homozygosis might increase TB
      risk in the overall analysis (T vs. C: OR 1.30, 95%CI 1.03-1.64, P = 0.03 and TT
      vs. CC+CT: OR 1.52, 95%CI 1.12-2.08, P = 0.01). Similar correlations were
      observed among human immunodeficiency virus negative subjects. Strong
      associations were also found between CD14-159C/T and TB in Asians. Asian
      individuals with the T-allele and the TT genotype had a significantly increased
      risk of TB (T vs. C: OR 1.46, 95%CI 1.27-1.68, P = 0.00; TT vs. CC: OR 1.83,
      95%CI 1.38-2.44, P = 0.00 and TT vs. CC+CT: OR 1.84, 95%CI 1.55-2.19, P = 0.00).
      No associations were detected in the pulmonary TB and extra-pulmonary TB groups.
      CONCLUSION: CD14-159C/T contributes to TB susceptibility; the T-allele and TT
      homozygosis are potential risk factors, particularly in Asians.

PMID- 24125454
TI  - Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet
      Nam.
AB  - SETTING: The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based
      on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis.
      However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this
      target and this undermines the validity of these molecular tests. OBJECTIVE: We
      quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet
      Nam and studied their epidemiological and clinical characteristics. DESIGN:
      Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted
      two sputum samples for culture, IS6110 restriction fragment length polymorphism
      (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase
      chain reaction (PCR) was performed to confirm the absence of IS6110 elements in
      strains lacking IS6110 hybridisation in RFLP. RESULTS: Among 2664 TB patient
      isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains,
      these no-copy strains were less often resistant to anti-tuberculosis drugs,
      particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed
      significant geographic variation. No associations with TB history or demographic
      factors were found. CONCLUSIONS: Strains without the IS6110 target pose a problem
      in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to
      other strains circulating in Viet Nam, no-copy strains are more susceptible to
      anti-tuberculosis drugs.

PMID- 24125456
TI  - First proficiency testing of second-line anti-tuberculosis drug susceptibility
      testing in 12 provinces of China.
AB  - OBJECTIVE: To evaluate the performance of drug susceptibility testing (DST)
      against the main second-line (SL) anti-tuberculosis drugs in tuberculosis (TB)
      laboratories in China. METHOD: The supranational TB reference laboratory issued
      30 Mycobacterium tuberculosis isolates to the participating laboratories. Each
      participating laboratory performed DST against kanamycin (KM), amikacin (AMK),
      capreomycin (CPM) and ofloxacin (OFX) using the proportion method in Lowenstein
      Jensen medium per World Health Organization recommendations. Reported results
      were checked and compared with the judicial results. RESULT: The main performance
      indicators for the four anti-tuberculosis drugs evaluated (KM, AMK, CPM, OFX)
      were as follows: accordance rates: 91.62%, 99.16%, 96.93% and 96.37%;
      reproducibility: 99.16%, 99.16%, 94.96% and 94.12%; specificity: 99.12%, 99.64%,
      98.00% and 98.41%; sensitivity: 78.03%, 97.62%, 94.44% and 91.51%. The accordance
      rates and sensitivity values of the four drugs showed statistically significant
      differences, while specificities showed no significant differences. CONCLUSION:
      Eight (66.7%) participating laboratories met the set requirement criteria;
      however, DST in four (33.3%) laboratories requires greater attention. Of the four
      drugs tested, the results for KM were lower than those for the other drugs.
      External quality assessment can lead to effective evaluation of laboratory
      performance in SL DST.

PMID- 24125455
TI  - Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against
      pyrazinamide: the Swedish experience.
AB  - BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis
      (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of
      Mycobacterium tuberculosis against PZA is not included in the World Health
      Organization's yearly proficiency testing. There is an increasing need to
      establish quality control of PZA DST. OBJECTIVE: To evaluate the performance of
      PZA DST and to introduce a quality assurance system for the test in Sweden.
      METHOD: Panels with PZA-susceptible and -resistant isolates were used in three
      rounds of proficiency testing in all five Swedish clinical TB laboratories and
      our reference laboratory. All laboratories used the MGIT 960 system. Minimum
      inhibitory concentrations (MICs) were determined and the pncA gene was sequenced
      to further characterise the 52 panel strains. RESULTS: Good agreement was seen
      between the phenotypic PZA DST and pncA sequence data, and MIC determination
      confirmed high levels of resistance. However, in contrast to other drugs, for
      which correct proficiency test results were observed, specificity problems
      occurred for PZA DST in some laboratories. CONCLUSIONS: In Sweden, using panel
      testing, differences were seen in the proficiency of TB laboratories in correctly
      identifying PZA susceptibility. Improved results were noted in the third round;
      PZA has therefore been included in yearly proficiency testing.

PMID- 24125457
TI  - Changes in vitamin C and oxidative stress status during the treatment of
      tuberculous meningitis.
AB  - BACKGROUND: Tuberculosis (TB) is associated with oxidative stress and is
      traditionally linked to vitamin C deficiency. OBJECTIVE: To evaluate the time
      course of the oxidative stress marker, malondialdehyde (MDA), and vitamin C
      status during the clinical treatment of tuberculous meningitis (TBM). METHOD: MDA
      and vitamin C reduction/oxidation (redox) status were spectrophotometrically
      measured at admission and during hospital treatment in cerebrospinal fluid (CSF)
      and serum from 27 TBM patients and 20 controls. RESULTS: Baseline CSF and serum
      MDA levels in TBM patients were higher than in controls (both P < 0.05), and
      remained elevated throughout the study. CSF MDA steadily increased from baseline
      0.66 +/- 0.24 mol/l to 1.02 +/- 0.33 MUmol/l at the end of the sixth week of
      treatment (P < 0.05), and then returned to baseline levels. Baseline CSF and
      serum total vitamin C were lower in TBM patients than in controls, but were soon
      normalised. CSF and serum ascorbate, reduced/oxidised vitamin C ratios and
      ascorbate CSF/serum ratio were markedly decreased in TBM patients (P < 0.05), and
      showed no improvement during treatment. CONCLUSION: These results indicate
      increased local and systemic oxidative stress, accompanied by impaired redox
      status, but not total vitamin C deficiency, which persisted during conventional
      clinical treatment of TBM.

PMID- 24125458
TI  - Indoleamine 2,3-dioxygenase in the pathogenesis of tuberculous pleurisy.
AB  - BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such
      as lung cancer and infectious diseases, including pulmonary tuberculosis (TB).
      The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the
      kynurenine pathway, and is considered a crucial immunoregulatory molecule
      mediating immune tolerance. Recent studies have shown IDO activity to be a novel
      prognostic factor not only in cancer patients but also in those with infectious
      diseases, including pneumonia and pulmonary TB. However, no studies have measured
      and determined the clinical significance of IDO activity in pleural fluid.
      METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP),
      36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was
      evaluated using liquid chromatography/electrospray ionisation tandem mass
      spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio.
      RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine
      concentrations and significantly lower tryptophan concentrations, resulting in
      significantly higher IDO activity compared with pleural effusion or serum from
      non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed
      enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry.
      CONCLUSIONS: These results suggest that IDO is strongly involved in the
      pathogenesis of TBP.

PMID- 24125459
TI  - Association between metabolic syndrome and rate of lung function decline: a
      longitudinal analysis.
AB  - SETTING: Factors that influence the annual rate of decline of lung function need
      to be verified. OBJECTIVE: To determine the effects of metabolic syndrome,
      especially hypertension, on the annual rate of decline in lung function. DESIGN:
      A total of 635 healthy participants without known respiratory disease completed
      baseline and follow-up routine check-ups, including a pulmonary function test,
      for at least 3 years. Age, sex, height, weight, waist circumference, smoking
      status, other underlying diseases, and pulmonary function and blood test results
      were carefully reviewed. RESULTS: In a multivariable analysis of baseline data,
      diabetes was associated with lower forced vital capacity (FVC). In longitudinal
      analysis using mixed linear regression, hypertension was an independent predictor
      for acceleration of FVC decline rate compared to subjects without hypertension (
      37.2 vs. -18.5 ml/year), while anti-hypertensive medication decelerated FVC
      decline in hypertensive subjects (-58.9 vs. -32.3 ml/year). The annual rate of
      decline in forced expiratory volume in 1 second (FEV1) in groups with and without
      hypertension did not differ significantly. No significant difference was found in
      FEV1 or FVC annual rates of decline with regard to the presence of diabetes,
      dyslipidaemia, obesity or abdominal obesity. CONCLUSION: Hypertension is
      associated with an accelerated decline in FVC, but anti-hypertensive medication
      might abate the rate of decline in asymptomatic healthy subjects.

PMID- 24125460
TI  - [An early onset and aggressive form of amyloid angiopathy].

PMID- 24125461
TI  - Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.
AB  - This historical article describes the life and work of the British physician
      Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest
      neurologists of the first half of the 20th century. Early in his career, Wilson
      spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicetre
      Hospital. He subsequently retained uninterrupted links with French neurology. He
      also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson
      returned to London, where he worked for the rest of his life at the National
      Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous
      Diseases, and today the National Hospital for Neurology and Neurosurgery) in
      Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor
      system and the new', on disorders of motility and muscle tone, on the epilepsies,
      on aphasia, apraxia, tics, and pathologic laughing and crying, and most
      importantly on Wilson's disease. The other objective of our paper is to
      commemorate the centenary of Wilson's most important work published in 1912 in
      Brain, and also in Revue Neurologique, on an illness newly recognized and
      characterized by him entitled "Progressive lenticular degeneration, a familial
      nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases,
      four of whom he followed himself, but also four cases previously published by
      others and a further two that he considered in retrospect had the same disease as
      he was describing. The pathological profile combined necrotic damage in the
      lenticular nuclei of the brain and hepatic cirrhosis. This major original work is
      summarized and discussed in the present paper. Wilson not only delineated what
      was later called hepato-lenticular degeneration and Wilson's disease, but also
      introduced for the first time the terms extrapyramidal syndrome and
      extrapyramidal system, stressing the role of the basal ganglia in motility. The
      present historical work emphasizes the special contributions made by Wilson to
      the study of movement disorders, including akinesia and bradykinesia in
      Parkinson's disease, and their relation to basal ganglia pathology. 

PMID- 24125462
TI  - [Is MRI monitoring useful in clinical practice in patients with multiple
      sclerosis? No].
AB  - Is regular MRI monitoring useful in clinical practice in multiple sclerosis
      patients treated with disease modifying therapy (DMT) drugs? My answer is no.
      Tacking a DMT drug is not by itself a pertinent criterion for requiring a
      systematic MRI monitoring in MS patients. Five clinical criteria should be taken
      into consideration before prescribing regular MRI examinations. The clinical form
      of the disease: MRI monitoring in DMT treated patients, has been demonstrated as
      useful only in pure relapsing-remitting MS patients. Up to now, there is no
      convincing demonstration of therapeutic efficacy with any DMT drug, neither first
      line nor second-line drugs in patients with primary or secondary progressive MS
      disease. The duration of the disease, epidemiological data leading to the concept
      of a two-stage disability progression in MS, emphasizes the importance of
      treating as early as possible RRMS patients in order to stop accumulation of new
      focal MRI CNS lesions. In this regard, an annual monitoring for the 5 first years
      of the disease looks reasonable in order to better personalize the treatment
      choice among the few approved DMT drugs. The duration of the treatment: a first
      MRI assessment at month 6 after initiating a new DMT drug is adequate in order to
      better distinguish responder versus no responder. The persistence of Gado+lesions
      at 6 months is a strong indication for considering alternative treatment. The
      disease activity: both criteria, clinical and MRI, are needed to recognized very
      active or aggressive relapsing MS patients, leading to decide a rapid use of
      second-line treatment therapy. The treatment choice: in JC positive MS patients
      treated with natalizumab, the risk of PML is as high as more than 1 % in those
      JC+MS patients that are treated continuously more than 24 months. A regular MRI
      monitoring (3 or 6months) is recommended in order to detect as early as possible
      MRI abnormalities suggesting PML.

PMID- 24125463
TI  - [Natalizumab as induction therapy in multiple sclerosis].
AB  - BACKGROUND: Current treatment options for first-line immunotherapy in relapsing
      remitting multiple sclerosis (MS) are recombinant interferon-beta and glatiramer
      acetate. However, these therapies are only partially effective and certain
      patients may fail to respond. For this reason, it is important to elaborate
      alternative treatment strategies. Induction therapy represents a more aggressive
      approach in which powerful drugs are used right from the beginning to tackle the
      disease process hard and early. Natalizumab is a powerful monoclonal antibody
      approved for the treatment of relapsing-remitting MS and is known to silence
      disease activity. METHODS: We describe here the early outcome at 1 month and at 6
      months of three patients treated with natalizumab for relapsing-remitting MS.
      RESULTS: All three patients had a high disease activity before the initiation of
      natalizumab, with 4, 8 and 5 gadolinium-enhancing lesions on brain MRI
      respectively. On the MRI scans made at 1 month after the first infusion, and at 6
      months, there was no more gadolinium-enhancement and no new T2-lesion.
      Clinically, they did not experience any relapse. DISCUSSION: In these three
      cases, natalizumab showed a dramatic efficacy: the patients became "disease
      activity free" right from the first infusion. To our knowledge, natalizumab is
      not classically used as an induction therapy, unlike mitoxantrone. However, this
      treatment has potential hematological and cardiac toxicity and its use can be
      limited. Thus, in JC virus negative patients, natalizumab could be an interesting
      alternative treatment. CONCLUSION: Our report suggests that induction strategy
      with natalizumab may be applicable in patients with aggressive multiple
      sclerosis. A study of more similar cases may be interesting to confirm these
      preliminary results.

PMID- 24125464
TI  - Big data, aging, and dementia: pathways for international harmonization on data
      sharing.

PMID- 24125465
TI  - Consulting communities on feedback of genetic findings in international health
      research: sharing sickle cell disease and carrier information in coastal Kenya.
AB  - BACKGROUND: International health research in malaria-endemic settings may include
      screening for sickle cell disease, given the relationship between this important
      genetic condition and resistance to malaria, generating questions about whether
      and how findings should be disclosed. The literature on disclosing genetic
      findings in the context of research highlights the role of community consultation
      in understanding and balancing ethically important issues from participants'
      perspectives, including social forms of benefit and harm, and the influence of
      access to care. To inform research practice locally, and contribute to policy
      more widely, this study aimed to explore the views of local residents in Kilifi
      County in coastal Kenya on how researchers should manage study-generated
      information on sickle cell disease and carrier status. METHODS: Between June 2010
      and July 2011, we consulted 62 purposively selected Kilifi residents on how
      researchers should manage study-generated sickle cell disease findings. Methods
      drew on a series of deliberative informed small group discussions. Data were
      analysed thematically, using charts, to describe participants' perceptions of the
      importance of disclosing findings, including reasoning, difference and underlying
      values. Themes were derived from the underlying research questions and from
      issues emerging from discussions. Data interpretation drew on relevant areas of
      social science and bioethics literature. RESULTS: Perceived health and social
      benefits generated strong support for disclosing findings on sickle cell disease,
      but the balance of social benefits and harms was less clear for sickle cell
      trait. Many forms of health and social benefits and harms of information-sharing
      were identified, with important underlying values related to family interests and
      the importance of openness. The influence of micro and macro level contextual
      features and prioritization of values led to marked diversity of opinion.
      CONCLUSIONS: The approach demonstrates a high ethical importance in many malaria
      endemic low-to-middle income country settings of disclosing sickle cell disease
      findings generated during research, alongside provision of effective care and
      locally-informed counselling. Since these services are central to the benefits of
      disclosure, health researchers whose studies include screening for sickle cell
      disease should actively promote the development of health policy and services for
      this condition in situations of unmet need, including through the prior
      development of collaborative partnerships with government health managers and
      providers. Community consultation can importantly enrich ethical debate on
      research practice where in-depth exploration of informed views and the potential
      for difference are taken into account.

PMID- 24125466
TI  - Metallothionein immunoexpression in selected benign epithelial odontogenic
      tumors.
AB  - BACKGROUND: Odontogenic tumors exhibited variable biologica behaviors.
      Metallothionein (MT) is correlated with the cellular homeostasis of essential
      metals, cellular differentiation, and proliferation. The core goals of this study
      are (i) to report and to compare MT expression among benign epithelial
      odontogenic tumors; (ii) to correlate MT with cellular proliferation index; and
      (iii) to evaluate the influence of the inflammatory infiltrate on MT expression.
      MATERIALS AND METHODS: Ten cases of solid ameloblastomas (SABs), 4 squamous
      odontogenic tumors (SOTs), 5 adenomatoid odontogenic tumors (AOTs), and 3
      calcifying epithelial odontogenic tumors (CEOTs) were subjected to
      immunohistochemical to anti-MT, anti-Ki-67, and anti-PCNA. Statistical analysis
      was performed using BioEstat((r)) 4.0. RESULTS: Metallothionein staining was
      found to be the highest in the SABs (93.1%), followed by SOTs (52.9%), AOTs
      (38.4%), and CEOTs (0%). MT staining exhibited statistically significant
      differences between the SABs and the SOTs (P = 0.0047) and the AOTs (P = 0.0022).
      A weak-to-strong positive correlation between IMT and IK or IP was observed in
      SABs and SOTs, whereas a strong negative correlation was observed in AOTs. No
      differences in IMT, IK, and IP were observed between inflammation groups A and B.
      CONCLUSIONS: The increased MT expression observed in the SABs might be correlated
      with clinical behavior (local invasiveness and high rate of recurrence). In the
      SABs and SOTs, MT plays a role in the stimulation of cellular proliferation. In
      contrast, MT can inhibit cellular proliferation in the AOT. The IMT, IK, and IP
      are not affected by inflammation.

PMID- 24125468
TI  - In vitro and in silico analysis of the Aspergillus nidulans DNA-CreA repressor
      interactions.
AB  - The CreA protein mediates carbon catabolite repression in the fungus Aspergillus
      nidulans. Its DNA-binding domain belongs to the Cys2-His2 class, binding
      specifically to a 5' SYGGRG 3' nucleotide sequence. EMSA experiments showed that
      the CreA(G27D) mutation resulted in a 30-fold increase of the Kdiss, and
      footprinting revealed a altered pattern of protein/DNA contacts. We modeled the
      CreA and the CreA(G27D) complexes in silico. A 15 ns molecular dynamics
      simulation of the solvated CreA(G27D) and CreA models was carried out using the
      MOE 2007.09 suite and the Amber99 force field. We have focused our analysis in
      residues Arg14, Glu16, His17, and Arg20 and Arg44, Asp46, and Arg50, previously,
      shown to be responsible for the specific contacts of the two Zn fingers. The
      electrostatic and the total potential energies showed the CreA(G27D) mutation to
      decrease the affinity of the complex, in agreement with the Kdiss's values. The
      in silico approach highlighted the role of the inter-finger linker. We identified
      several differential structural characteristics of the CreA and CreA(G27D)/DNA
      complexes and observed that the latter resulted in a lower dynamic flexibility of
      the complex. 

PMID- 24125467
TI  - Mechanism and regulation of kinesin-5, an essential motor for the mitotic
      spindle.
AB  - Mitotic cell division is the most fundamental task of all living cells. Cells
      have intricate and tightly regulated machinery to ensure that mitosis occurs with
      appropriate frequency and high fidelity. A core element of this machinery is the
      kinesin-5 motor protein, which plays essential roles in spindle formation and
      maintenance. In this review, we discuss how the structural and mechanical
      properties of kinesin-5 motors uniquely suit them to their mitotic role. We
      describe some of the small molecule inhibitors and regulatory proteins that act
      on kinesin-5, and discuss how these regulators may influence the process of cell
      division. Finally, we touch on some more recently described functions of kinesin
      5 motors in non-dividing cells. Throughout, we highlight a number of open
      questions that impede our understanding of both this motor's function and the
      potential utility of kinesin-5 inhibitors. 

PMID- 24125470
TI  - Magnetic field strength and reproducibility of neodymium magnets useful for
      transcranial static magnetic field stimulation of the human cortex.
AB  - OBJECTIVE: The application of transcranial static magnetic field stimulation
      (tSMS) in humans reduces the excitability of the motor cortex for a few minutes
      after the end of stimulation. However, when tSMS is applied in humans, the cortex
      is at least 2 cm away, so most of the strength of the magnetic field will not
      reach the target. The main objective of the study was to measure the strength and
      reproducibility of static magnetic fields produced by commercial neodymium
      magnets. METHODS: We measured the strength and reproducibility of static magnetic
      fields produced by four different types of neodymium cylindrical magnets using a
      magnetic field-to-voltage transducer. RESULTS: Magnetic field strength depended
      on magnet size. At distances <1.5 cm, the magnetic field strength was affected by
      the presence of central holes (potentially useful for recording
      electroencephalograms). At distances >1.5 cm, the measurements made on the
      cylinder axis and 1.5 cm off the axis were comparable. The reproducibility of the
      results (i.e., the consistency of the field strength across magnets of the same
      size) was very high. CONCLUSIONS: These measurements offer a quantitative
      empirical reference for developing devices useful for tSMS protocols in both
      humans and animals.

PMID- 24125469
TI  - NumbL is essential for Xenopus primary neurogenesis.
AB  - BACKGROUND: Members of the vertebrate Numb family of cell fate determinants serve
      multiple functions throughout early embryogenesis, including an essential role in
      the development of the nervous system. The Numb proteins interact with various
      partner proteins and correspondingly participate in multiple cellular activities,
      including inhibition of the Notch pathway. RESULTS: Here, we describe the
      expression characteristics of Numb and Numblike (NumbL) during Xenopus
      development and characterize the function of NumbL during primary neurogenesis.
      NumbL, in contrast to Numb, is expressed in the territories of primary
      neurogenesis and is positively regulated by the Neurogenin family of proneural
      transcription factors. Knockdown of NumbL afforded a complete loss of primary
      neurons and did not lead to an increase in Notch signaling in the open neural
      plate. Furthermore, we provide evidence that interaction of NumbL with the AP-2
      complex is required for NumbL function during primary neurogenesis. CONCLUSION:
      We demonstrate an essential role of NumbL during Xenopus primary neurogenesis and
      provide evidence for a Notch-independent function of NumbL in this context.

PMID- 24125471
TI  - Ultrasensitive nanoporous interferometric sensor for label-free detection of
      gold(III) ions.
AB  - In this study, we present an ultrasensitive sensor based on nanoporous anodic
      alumina (NAA) for detection of gold(III) ions (Au(3+) ions) using reflectometric
      interference spectroscopy (RIfS). Nanoporous anodic alumina, prepared by two-step
      electrochemical anodization, was functionalized with 3-mercaptopropyl
      tirethoxysilane (MPTES) in order to selectively detect Au(3+) ions. Thus
      prepared, MPTES-NAA sensors were exposed to different concentrations of Au(3+)
      ions ranging from 0.1 to 750 MUM and the changes in the effective optical
      thickness (DeltaEOT) were monitored in real-time. The linear range of these
      Au(3+) sensors was from 0.1 to 80 MUM, with a lower detection limit of 0.1 MUM of
      Au(3+) ions. Furthermore, the specificity of these MPTES-NAA sensors was
      validated by sequential exposure to 40 MUM solutions of Fe(3+,) Mg(2+), Co(2+),
      Cu(2+), Ni(2+), Ag(+), and Pb(2+), resulting in negligible changes in EOT as
      compared to the same concentration of Au(3+) ions. Detection of Au(3+) ions in
      complex and environmentally and biologically relevant solvents such as tap water
      and phosphate buffer solution (PBS) was also successfully carried out in order to
      demonstrate the real-life application of these sensors. Finally, the binding
      isotherm for Au(3+) ions and thiol (SH) group of MPTES-NAA system was determined
      by fitting the changes in EOT to Freundlich and Langmuir isotherm models. 

PMID- 24125474
TI  - Drug development for the management of organophosphorus poisoning.
AB  - INTRODUCTION: The continuous application of organophosphate pesticides in
      developing countries, in addition to the remaining stock piles of chemical
      warfare nerve agents and their possible use is a significant threat to the
      public. Yet, today's options for a treatment of organophosphorus poisonings are
      still inadequate. AREAS COVERED: This article provides a concise overview of
      current and future research trying to improve both prophylaxis and treatment of
      organophosphorus intoxications. The authors provide a summary of current oxime
      therapy and highlight several new concepts to overcome existing gaps. This
      overview of therapeutic options is accompanied by two sections on cyclodextrins,
      related compounds and bioscavengers, which may be used for either prophylaxis or
      treatment. For both groups, the authors review current drug design and screening
      approaches, the resulting developments and future challenges. EXPERT OPINION:
      While the search for one multipotent oxime has been a fruitless endeavor,
      combination of multiple oximes with complemental and systemic reactivity appears
      as a valuable concept. Development of potential scavengers, be it cyclodextrins
      or bioscavengers, is still hampered by insufficient efficacy of these compounds.
      Future strategies will aim at improving their catalytic efficacy while minimizing
      immunogenicity.

PMID- 24125473
TI  - Probing anisotropic structure changes in proteins with picosecond time-resolved
      small-angle X-ray scattering.
AB  - We have exploited the principle of photoselection and the method of time-resolved
      small-angle X-ray scattering (SAXS) to investigate protein size and shape changes
      following photoactivation of photoactive yellow protein (PYP) in solution with
      ~150 ps time resolution. This study partially overcomes the orientational average
      intrinsic to solution scattering methods and provides structural information at a
      higher level of detail. Photoactivation of the p-coumaric acid (pCA) chromophore
      in PYP produces a highly contorted, short-lived, red-shifted intermediate (pR0),
      and triggers prompt, protein compaction of approximately 0.3% along the direction
      defined by the electronic transition dipole moment of the chromophore.
      Contraction along this dimension is accompanied by expansion along the orthogonal
      directions, with the net protein volume change being approximately -0.25%. More
      than half the strain arising from formation of pR0 is relieved by the pR0 to pR1
      structure transition (1.8 +/- 0.2 ns), with the persistent strain presumably
      contributing to the driving force needed to generate the spectroscopically blue
      shifted pB signaling state. The results reported here are consistent with the
      near-atomic resolution structural dynamics reported in a recent time-resolved
      Laue crystallography study of PYP crystals and suggest that the early time
      structural dynamics in the crystalline state carry over to proteins in solution. 

PMID- 24125472
TI  - Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents
      inflammatory bone loss in vivo.
AB  - BACKGROUND AND PURPOSE: Osteoclasts play a pivotal role in diseases such as
      osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching
      for natural compounds that may suppress osteoclast formation and/or function is
      promising for the treatment of osteoclast-related diseases. Here, we examined
      changes in osteoclastogenesis and LPS-induced osteolysis in response to
      andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese
      and Indian medicinal plant Andrographis paniculata. EXPERIMENTAL APPROACH:
      Effects of AP on osteoclast differentiation and bone resorption were measured in
      vitro. Western blots and RT-PCR techniques were used to examine the underlying
      molecular mechanisms. The bone protective activity of AP in vivo was assessed in
      a mouse model of osteolysis. KEY RESULTS: AP concentration-dependently suppressed
      RANKL-mediated osteoclast differentiation and bone resorption in vitro and
      reduced the expression of osteoclast-specific markers, including tartrate
      resistant acid phosphatase, calcitonin receptors and cathepsin K. Further
      molecular analysis revealed that AP impaired RANKL-induced NF-kappaB signalling
      by inhibiting the phosphorylation of TGF-beta-activated kinase 1, suppressing the
      phosphorylation and degradation of IkappaBalpha, and subsequently preventing the
      nuclear translocation of the NF-kappaB p65 subunit. AP also inhibited the
      ERK/MAPK signalling pathway without affecting p38 or JNK signalling. CONCLUSIONS
      AND IMPLICATIONS: AP suppressed RANKL-induced osteoclastogenesis through
      attenuating NF-kappaB and ERK/MAPK signalling pathways in vitro, thus preventing
      bone loss in vivo. These data indicated that AP is a promising natural compound
      for the treatment of osteoclast-related bone diseases.

PMID- 24125475
TI  - Increased number and frequency of group 3 innate lymphoid cells in nonlesional
      psoriatic skin.
AB  - BACKGROUND: Psoriasis is a common immune-mediated inflammatory disease that
      affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play
      key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid
      cells (ILCs) with a high capacity to produce IL-17 and/or IL-22 have recently
      been identified and associated with inflammatory bowel diseases. The occurrence
      and role of ILCs in human skin are poorly understood. OBJECTIVES: To describe the
      prevalence of the different ILC subpopulations in skin from healthy controls and
      patients with psoriasis or allergy to nickel. METHODS: Skin biopsies were taken
      from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and
      petrolatum-exposed skin from patients with contact allergy to nickel, and
      lymphocytes were isolated. The cells were stained and characterized by flow
      cytometry. Cytokine and ligand mRNA expression were measured by quantitative
      polymerase chain reaction. RESULTS: We found that members of the three groups of
      ILCs were present in human skin. Remarkably, the number and frequency of
      RORgammat(+) CD56(+) ILC3s, which are known to produce IL-22, were elevated in
      both nonlesional and lesional skin from patients with psoriasis compared with
      healthy skin and skin from patients with contact allergy to nickel. Furthermore,
      skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds
      to stress-induced ligands, including major histocompatibility complex class I
      related chain A, which we found to be strongly upregulated in lesional skin from
      patients with psoriasis. CONCLUSION: These results show that ILCs are present in
      human skin and indicate that RORgammat(+) CD56(+) ILC3 may be involved in the
      pathogenesis of psoriasis.

PMID- 24125477
TI  - Life cycle water use of energy production and its environmental impacts in China.
AB  - The energy sector is a major user of fresh water resources in China. We
      investigate the life cycle water withdrawals, consumptive water use, and
      wastewater discharge of China's energy sectors and their water-consumption
      related environmental impacts, using a mixed-unit multiregional input-output
      (MRIO) model and life cycle impact assessment method (LCIA) based on the Eco
      indicator 99 framework. Energy production is responsible for 61.4 billion m(3)
      water withdrawals, 10.8 billion m(3) water consumption, and 5.0 billion m(3)
      wastewater discharges in China, which are equivalent to 12.3%, 4.1% and 8.3% of
      the national totals, respectively. The most important feature of the energy-water
      nexus in China is the significantly uneven spatial distribution of consumptive
      water use and its corresponding environmental impacts caused by the geological
      discrepancy among fossil fuel resources, fresh water resources, and energy
      demand. More than half of energy-related water withdrawals occur in the east and
      south coastal regions. However, the arid north and northwest regions have much
      larger water consumption than the water abundant south region, and bear almost
      all environmental damages caused by consumptive water use. 

PMID- 24125478
TI  - Using Algorithmic Practice Maps to Teach Emergency Preparedness Skills to Nurses.

PMID- 24125480
TI  - Platinum-catalyzed C-H arylation of simple arenes.
AB  - This report describes the Na2PtCl4 catalyzed C-H arylation of arene substrates
      with diaryliodonium salts. The site selectivity of these reactions is
      predominantly controlled by steric factors. Remarkably, Na2PtCl4-catalyzed
      naphthalene arylation proceeds with opposite site selectivity compared to that
      obtained with Na2PdCl4 as the catalyst. Preliminary mechanistic studies provide
      evidence for a Pt(II)/Pt(IV) catalytic cycle involving rate-limiting C-C bond
      forming reductive elimination. 

PMID- 24125479
TI  - Self-structure and emotional experience.
AB  - Two studies examine individual differences in affective reactivity by linking
      emotional experience to cognitive self-structure. Consistent with the view that
      individuals with an evaluative compartmentalised self-structure are emotionally
      reactive, we find that evaluative compartmentalisation is associated with the
      experience of, and desire for, high-arousal positive (HAP) affect, whereas
      evaluative integration is associated with the experience of low-arousal positive
      (LAP) and low-arousal negative affect and the desire for LAP affect. Although
      compartmentalised individuals are less granular in their tendency to report
      experiencing both HAP and LAP, they are strongly differentiated in their
      perceptions of high-arousal states as positive and low-arousal states as
      negative. Thus, compartmentalised individuals' reactivity may be explained by
      their preference for HAP states and the 'breadth' of their emotionality (e.g.,
      the tendency to experience sadness and nervousness at the same time). 

PMID- 24125481
TI  - Pupal cocoons affect sanitary brood care and limit fungal infections in ant
      colonies.
AB  - BACKGROUND: The brood of ants and other social insects is highly susceptible to
      pathogens, particularly those that penetrate the soft larval and pupal cuticle.
      We here test whether the presence of a pupal cocoon, which occurs in some ant
      species but not in others, affects the sanitary brood care and fungal infection
      patterns after exposure to the entomopathogenic fungus Metarhizium brunneum. We
      use a) a comparative approach analysing four species with either naked or
      cocooned pupae and b) a within-species analysis of a single ant species, in which
      both pupal types co-exist in the same colony. RESULTS: We found that the presence
      of a cocoon did not compromise fungal pathogen detection by the ants and that
      species with cocooned pupae increased brood grooming after pathogen exposure. All
      tested ant species further removed brood from their nests, which was
      predominantly expressed towards larvae and naked pupae treated with the live
      fungal pathogen. In contrast, cocooned pupae exposed to live fungus were not
      removed at higher rates than cocooned pupae exposed to dead fungus or a sham
      control. Consistent with this, exposure to the live fungus caused high numbers of
      infections and fungal outgrowth in larvae and naked pupae, but not in cocooned
      pupae. Moreover, the ants consistently removed the brood prior to fungal
      outgrowth, ensuring a clean brood chamber. CONCLUSION: Our study suggests that
      the pupal cocoon has a protective effect against fungal infection, causing an
      adaptive change in sanitary behaviours by the ants. It further demonstrates that
      brood removal-originally described for honeybees as "hygienic behaviour"-is a
      widespread sanitary behaviour in ants, which likely has important implications on
      disease dynamics in social insect colonies.

PMID- 24125482
TI  - Implementing disability evaluation and welfare services based on the framework of
      the International Classification of Functioning, Disability and Health:
      experiences in Taiwan.
AB  - BACKGROUND: Before 2007, the disability evaluation was based on the medical model
      in Taiwan. According to the People with Disabilities Rights Protection Act, from
      2012 the assessment of a person's eligibility for disability benefits has to be
      determined based on the International Classification of Functioning, Disability,
      and Health (ICF) framework nationwide. The purposes of this study were to: 1)
      design the evaluation tools for disability eligibility system based on the
      ICF/ICF-Children and Youth; 2) compare the differences of grades of disability
      between the old and new evaluation systems; 3) analyse the outcome of the new
      disability evaluation system. METHODS: To develop evaluation tools and procedure
      for disability determination, we formed an implementation taskforce, including
      199 professional experts, and conducted a small-scale field trial to examine the
      feasibility of evaluation tools in Phase I. To refine the evaluation tools and
      process and to compare the difference of the grades of disability between new and
      old systems, 7,329 persons with disabilities were randomly recruited in a
      national population-based study in Phase II. To implement the new system smoothly
      and understand the impact of the new system, the collaboration mechanism was
      established and data of 168,052 persons who applied for the disability benefits
      was extracted from the information system and analysed in Phase III. RESULTS: The
      measures of the 43 categories for body function/structure components, the
      Functioning Scale of Disability Evaluation System for activities/participation
      components, and the needs assessment have been developed and used in the field
      after several revisions. In Phase II, there was 49.7% agreement of disability
      grades between the old and new systems. In Phase III, 110,667 persons with a
      disability received their welfare services through the new system. Among them,
      77% received basic social welfare support, 89% financial support, 24% allowance
      for assistive technology, 7% caregiver support, 8% nursing care and
      rehabilitation services at home, and 47% were issued parking permits for persons
      with disability. CONCLUSION: This study demonstrated that disability evaluation
      system based on the ICF could provide a common language between disability
      assessment, needs assessment and welfare services. However, the proposed
      assessment protocol and tools require additional testing and validation.

PMID- 24125483
TI  - Effect of mineralocorticoid receptor antagonist on insulin resistance and
      endothelial function in obese subjects.
AB  - AIM: Obese individuals have high aldosterone levels that may contribute to
      insulin resistance (IR) and endothelial dysfunction leading to obesity-induced
      cardiovascular disease. We conducted a study to evaluate the effect of
      mineralocorticoid receptor antagonism on IR and endothelial function in obese
      individuals. This was a placebo-controlled, double-blind, randomized, parallel
      group study (NCT01406015). METHODS: Thirty-two non-diabetic, obese subjects [body
      mass index (BMI) 30 to 45 kg/m(2) ] with no other medical problems were
      randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo.
      Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial
      function by flow mediated vasodilatation (FMD) of brachial artery and renal
      plasma perfusion by clearance of para-aminohippurate (PAH). RESULTS: There was no
      change in weight, BMI or plasma potassium during the study period. Treatment with
      spironolactone led to increases in serum aldosterone (7.6 +/- 6.6 vs. 3.2 +/- 1.3
      ng/dl; p < 0.02, post-treatment vs. baseline) and urine aldosterone (11.0 +/- 7
      vs. 4.8 +/- 2.4 ug/g creatinine; p < 0.01) and decreases in systolic blood
      pressure (116 +/- 11 vs. 123 +/- 10 mmHg; p < 0.001). There were no changes in
      these variables in the placebo group. Neither spironolactone nor placebo
      treatment had a significant effect on ISI or other indices of glucose metabolism
      [insulin resistance by homeostatic model assessment (HOMA), area under the curve
      for insulin, area under the curve for glucose], brachial artery reactivity or the
      renal plasma perfusion values. Changes in these variables were similar in two
      groups. CONCLUSIONS: We conclude that 6 weeks of treatment with spironolactone
      does not change insulin sensitivity or endothelial function in normotensive obese
      individuals with no other comorbidities.

PMID- 24125484
TI  - 2-hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species.
AB  - The amino acid derivative 2-hydroxyisocaproic acid (HICA) is a nutritional
      additive used to increase muscle mass. Low levels can be detected in human plasma
      as a result of leucine metabolism. It has broad antibacterial activity but its
      efficacy against pathogenic fungi is not known. The aim was to test the efficacy
      of HICA against Candida and Aspergillus species. Efficacy of HICA against 19
      clinical and reference isolates representing five Candida and three Aspergillus
      species with variable azole antifungal sensitivity profiles was tested using a
      microdilution method. The concentrations were 18, 36 and 72 mg ml(-1) . Growth
      was determined spectrophotometrically for Candida isolates and by visual
      inspection for Aspergillus isolates, viability was tested by culture and impact
      on morphology by microscopy. HICA of 72 mg ml(-1) was fungicidal against all
      Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower
      concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA.
      HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus
      isolates and affected cell wall integrity. In conclusion, HICA has broad
      antifungal activity against Candida and Aspergillus at concentrations relevant
      for topical therapy. As a fungicidal agent with broad-spectrum bactericidal
      activity, it may be useful in the topical treatment of multispecies superficial
      infections. 

PMID- 24125486
TI  - Low-dose hypersensitivity and bystander effect are not mutually exclusive in A549
      lung carcinoma cells after irradiation with charged particles.
AB  - The purpose of this study was to measure survival fraction of A549 lung carcinoma
      cells irradiated with charged particles of various LET and to determine
      mechanisms responsible for enhanced cell killing in the low-dose region. A549
      cells were irradiated with a broadbeam of either 10 and 25 keV/MUm protons or 100
      keV/MUm alpha particles and then processed for clonogenic assays and phospho
      histone H3 staining. The survival fraction of unirradiated A549 cells co-cultured
      with irradiated cells was also evaluated. A549 cells were shown to exhibit low
      dose hypersensitivity (HRS) for both protons and alpha particles. The dose
      threshold at which HRS occurs decreased with increasing linear energy transfer
      (LET), whereas alphas, the initial survival curve slope, increased with
      increasing LET. In addition, the enhanced cell killing observed after irradiation
      with alpha particles was partly attributed to the bystander effect, due to the
      low proportion of hit cells at very low doses. Co-culture experiments suggest a
      gap junction-mediated bystander signal. Our results indicate that HRS is likely
      to be dependent on LET, and that a bystander effect and low-dose hypersensitivity
      may co-exist within a given cell line. 

PMID- 24125485
TI  - Phase II clinical trial of whole-brain irradiation plus three-dimensional
      conformal boost with concurrent topotecan for brain metastases from lung cancer.
AB  - BACKGROUND: Patients with brain metastases from lung cancer have poor prognoses
      and short survival time, and they are often excluded from clinical trials. Whole
      cranial irradiation is considered to be the standard treatment, but its efficacy
      is not satisfactory. The purpose of this phase II clinical trial was to evaluate
      the preliminary efficacy and safety of the treatment of whole-brain irradiation
      plus three-dimensional conformal boost combined with concurrent topotecan for the
      patients with brain metastases from lung cancer. METHODS: Patients with brain
      metastasis from lung cancer received concurrent chemotherapy and radiotherapy:
      conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day,
      2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with <=
      3 lesions with diameter >= 2 cm, a three-dimensional (3-D) conformal localised
      boost was given to increase the dosage to 56-60 Gy; and during radiotherapy,
      concurrent chemotherapy with topotecan was given (the chemoradiotherapy group,
      CRT). The patients with brain metastasis from lung cancer during the same period
      who received radiotherapy only were selected as the controls (the radiotherapy
      alone group, RT). RESULTS: From March 2009 to March 2012, both 38 patients were
      enrolled into two groups. The median progression-free survival(PFS) time , the 1-
      and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3
      months, 11.6%, 8.7% (chi2 = 6.02, p = 0.014), respectively. The 1- and 2-year
      intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% ,
      31.2% (chi2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival
      rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (chi2 = 1.811, p =
      0.178), respectively. The major side effects were myelosuppression and digestive
      toxicities, but no differences were observed between the two groups. CONCLUSION:
      Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal
      boost irradiation and concurrent topotecan chemotherapy significantly improved
      the PFS rate and the intracranial lesion control rate of patients with brain
      metastases from lung cancer, and no significant increases in side effects were
      observed. Based on these results, this treatment method is recommended for phase
      III clinical trial.

PMID- 24125488
TI  - Early tumor development captured through nondestructive, high resolution
      differential phase contrast X-ray imaging.
AB  - Although a considerable amount is known about molecular dysregulations in later
      stages of tumor progression, much less is known about the regulated processes
      supporting initial tumor growth. Insight into such processes can provide a fuller
      understanding of carcinogenesis, with implications for cancer treatment and risk
      assessment. Work from our laboratory suggests that organized substructure emerges
      during tumor formation. The goal here was to examine the feasibility of using
      state-of-the-art differential phase contrast X-ray imaging to investigate density
      differentials that evolve during early tumor development. To this end the
      beamline for TOmographic Microscopy and Coherent rAdiology experimenTs (TOMCAT)
      at the Swiss Light Source was used to examine the time-dependent assembly of
      substructure in developing tumors. Differential phase contrast (DPC) imaging
      based on grating interferometry as implemented with TOMCAT, offers sensitivity to
      density differentials within soft tissues and a unique combination of high
      resolution coupled with a large field of view that permits the accommodation of
      larger tissue sizes (1 cm in diameter), difficult with other imaging modalities. 

PMID- 24125487
TI  - Amelioration of radiation-induced pulmonary fibrosis by a water-soluble
      bifunctional sulfoxide radiation mitigator (MMS350).
AB  - A water-soluble ionizing radiation mitigator would have considerable advantages
      for the management of acute and chronic effects of ionizing radiation. We report
      that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a
      mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an
      effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total
      body irradiation of C57BL/6NHsd mice, significantly improving survival (P =
      0.0097). Furthermore, MMS350 (400 MUM) added weekly to drinking water after 20 Gy
      thoracic irradiation significantly decreased: expression of pulmonary
      inflammatory and profibrotic gene transcripts and proteins; migration into the
      lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors
      (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models)
      and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic
      and orally administered small molecule may be an effective therapeutic in
      clinical radiotherapy and as a counter measure against the acute and chronic
      effects of ionizing radiation. 

PMID- 24125489
TI  - Amaranth 7S globulin Langmuir films and its interaction with l-alpha
      dipalmitoilphosphatidilcholine at the air-fluid interface.
AB  - Amaranth seeds are one of the more promising food ingredients, due to their high
      protein content, among which the most important are storage proteins known as
      globulins. However, little is known about the physicochemical of the globulin
      proteins. In this work, we study the physicochemical behavior of films made of
      amaranth 7S globulin and its interaction with a model membrane made of L-alpha
      dipalmitoylphosphatidylcholine (L-alpha-DPPC) at the air-liquid interface. The
      study was done by means of Langmuir balance, Brewster angle microscopy (BAM),
      fluorescence microscopy, and atomic force microscopy (AFM). We found that
      isotherms of pure 7S globulin directly deposited on either water or buffer
      subphases behave similarly and globulin forms a condensed film made of globular
      and denature structures, which was confirmed by BAM observations. Good mixtures
      of the protein with L-alpha-DPPC are formed at low surface pressure. However,
      they phase separate from moderate to high surface pressure as observed by BAM.
      Isotherms detect the presence of the protein in the mixture with L-alpha-DPPC,
      but we were unable to detect it through BAM or AFM. We show that fluorescence
      microscopy is a very good technique to detect the presence of the protein when it
      is well-mixed within the LE phase of the lipid. AFM images clearly show the
      formation of protein mono- and multilayers, and in phase mode, we detected
      domains that are formed by protein and LE lipid phase, which were corroborated by
      fluorescence microscopy. We have shown that globulin 7S mix well with lipid
      phases, which could be important in food applications as stabilizers or
      emulsifiers, but we also show that they can phase separate with a moderate to
      high surface pressure.

PMID- 24125490
TI  - Thermoresponsive polymers as gene and drug delivery vectors: architecture and
      mechanism of action.
AB  - INTRODUCTION: This topic is important as it allows for improved specificity in
      drug delivery, providing possibilities for reduced side effects, and thereby
      improved pharmacotherapy. As a wealth of different polymers and mechanisms of
      action has been suggested, a systematic overview of the field is of current
      importance. AREAS COVERED: This article presents an overview over a selection of
      thermoresponsive polymers suitable as excipients in systems for gene and drug
      delivery with particular emphasis on the influence of polymer structure,
      composition, molecular weight (MW) and architecture on the responsive mechanisms.
      Due to the immense number of reports on these increasingly popular materials,
      focus has been restricted to the use of micelle-forming polymers with a lower
      critical solution temperature, temperature-responsive hydrogels for drug delivery
      applications and temperature-sensitive polymers as non-viral vectors for
      polynucleotide delivery. Specific examples covered are poly-(N
      isopropylacrylamide) (PNIPAAM), Pluronics and their derivatives. It is concluded
      that the studies constitute an excellent platform for development of
      thermoresponsive systems with improved gene and drug delivery properties. EXPERT
      OPINION: A thorough knowledge of factors important for loading efficiency and
      drug release is necessary to be able to develop optimal nano-carriers for the
      future. Other issues that are not fully understood is how small the carriers need
      to be, and which manufacturing procedures should be used.

PMID- 24125491
TI  - Option pricing: a flexible tool to disseminate shared savings contracts.
AB  - OBJECTIVES: Due to volatility in healthcare costs, shared savings contracts can
      create systematic financial losses for payers, especially when contracting with
      smaller providers. To improve the business case for shared savings, we calculated
      the prices of financial options that payers can "sell" to providers to offset
      these losses. STUDY DESIGN AND METHODS: Using 2009 to 2010 member-level total
      cost of care data from a large commercial health plan, we calculated option
      prices by applying a bootstrap simulation procedure. We repeated these
      simulations for providers of sizes ranging from 500 to 60,000 patients and for
      shared savings contracts with and without key design features (minimum savings
      thresholds,bonus caps, cost outlier truncation, and downside risk) and under
      assumptions of zero, 1%, and 2% real cost reductions due to the shared savings
      contracts. RESULTS: Assuming no real cost reduction and a 50% shared savings
      rate, per patient option prices ranged from $225 (3.1% of overall costs) for 500
      patient providers to $23 (0.3%) for 60,000-patient providers. Introducing minimum
      savings thresholds, bonus caps, cost outlier truncation, and downside risk
      reduced these option prices. Option prices were highly sensitive to the magnitude
      of real cost reductions. If shared savings contracts cause 2% reductions in total
      costs, option prices fall to zero for all but the smallest providers.
      CONCLUSIONS: Calculating the prices of financial options that protect payers and
      providers from downside risk can inject flexibility into shared savings
      contracts, extend such contracts to smaller providers, and clarify the tradeoffs
      between different contract designs, potentially speeding the dissemination of
      shared savings.

PMID- 24125492
TI  - Sources of information used in selection of surgeons.
AB  - OBJECTIVES: We explored the process of physician selection, focusing on selection
      of surgeons for knee and hip replacement to increase the probability of a new
      relationship, making cost and quality scorecard information more relevant. STUDY
      DESIGN: We collected data using a mailed survey sent to patients with knee or hip
      replacement surgery shortly after March 1, 2010. This time period followed a
      period of publicity about the new cost and quality scorecard. METHODS: We used
      multivariate probit models to predict awareness of the scorecard and willingness
      to switch providers. Multinomial logit methods were used to predict the primary
      factor influencing the choice of surgeon (physician referral, family or friend
      referral, surgeon location, previous experience with the surgeon, or other).
      RESULTS: Internet access and higher neighborhood incomes are associated with an
      increased probability of being aware of the scorecards. Male patients and
      patients with Internet access or in highly educated neighborhoods are more likely
      to be willing to switch providers for a reduced copay. Urban residents are more
      likely to rely on physician referrals, and rural patients on family/friend
      referrals when selecting a surgeon; Internet access reduces importance of surgeon
      location. CONCLUSIONS: Additional research is needed to determine whether
      Internet access is causal in improved responsiveness to market information and
      incentives, or a proxy for other factors. In addition, we see evidence that
      efforts to improve healthcare quality and costs through market forces should be
      tailored to the patient's place of residence.

PMID- 24125493
TI  - A natural experiment in mass media modulated pharmacokinetics after a change in
      tablet formulation.
AB  - BACKGROUND: After a new formulation of levothyroxine was distributed in Israel,
      side effects were reported to the Ministry of Health generating extensive media
      coverage. The purpose of this study was to determine whether the new formulation
      was associated with a change in thyroid-stimulating hormone (TSH) levels of
      treated patients and to evaluate the effect of the extensive media coverage on
      the incidence of laboratory test performance. STUDY DESIGN: Retrospective-cohort
      and crosssectional analysis. METHODS: All patients from the Leumit Health
      Services of Israel treated with levothyroxine between October 2009 and February
      2012 were included in the study. A retrospective cohort was constructed of
      patients treated and maintained within the desired target range (0.35-5 mIU/L)
      from January to July 2010. A longitudinal analysis was conducted to calculate the
      monthly distribution of TSH levels from laboratory tests during routine care over
      26 months. Data were stratified by cohort and noncohort patients. RESULTS: Data
      were captured for 18,106 levothyroxine-treated patients; 1140 were included into
      the retrospective cohort. In both subpopulations a sharp rise in the number of
      tests performed monthly is observed at the peak of media coverage during October
      and November 2011. In the retrospective cohort the proportion of TSH results
      within target range fell to a low of 67.5% during December 2011, with 25.3%
      between 5.01 and 20 mIU/L. Results>20 mIU/L then peaked at 3.8% indicating an
      increase in patients who stopped taking levothyroxine. CONCLUSIONS: These results
      demonstrate the power of mass media to influence patient behavior and to foment a
      public health scare.

PMID- 24125494
TI  - Anhydrous phosphoric Acid functionalized sintered mesoporous silica nanocomposite
      proton exchange membranes for fuel cells.
AB  - A novel inorganic proton exchange membrane based on phosphoric acid (PA)
      functionalized sintered mesoporous silica, PA-meso-silica, has been developed and
      investigated. After sintering at 650  degrees C, the meso-silica powder forms a
      dense membrane with a robust and ordered mesoporous structure, which is critical
      for retention of PA and water within the porous material. The PA-meso-silica
      membrane achieved a high proton conductivity of 5 * 10(-3) to 5 * 10(-2) S cm(-1)
      in a temperature range of 80-220  degrees C, which is between 1 and 2 orders of
      magnitudes higher than a typical membrane Nafion 117 or polybenzimidazole
      (PBI)/PA in the absence of external humidification. Furthermore, the PA-meso
      silica membranes exhibited good chemical stability along with high performance at
      elevated temperatures, producing a peak power density of 632 mW cm(-2) using a H2
      fuel at 190  degrees C in the absence of external humidification. The high
      membrane proton conductivity and excellent fuel cell performance demonstrate the
      utility of PA-meso-silica as a new class of inorganic proton exchange membranes
      for use in the high-temperature proton exchange membrane fuel cells (PEMFCs). 

PMID- 24125495
TI  - Investigation of cutaneous photoadaptation to narrowband ultraviolet B.
AB  - BACKGROUND: Photoadaptation describes the skin's ability to withstand an
      increased dose of ultraviolet (UV) radiation with repeated exposure, and this is
      the reason for exposure doses being increased during a course of phototherapy.
      However, directly measured data on photoadaptation are available only for
      broadband (BB) and not narrowband (NB)-UVB. OBJECTIVES: To measure
      photoadaptation to narrowband UVB. METHODS: We measured the degree of
      photoadaptation in patients with psoriasis during a standard course of NB-UVB
      phototherapy. The minimal erythemal dose (MED) was measured before and towards
      the end of a course of phototherapy. An adaptation factor (AF) was calculated for
      each patient using the ratio of final MED to initial MED. Sigmoid dose-response
      curves were also constructed. RESULTS: MED results were available for 50 patients
      (mean age 44 years, 28 female). The mean AF was 2.7 (95% confidence interval 2.4
      3.0). There was no significant correlation between AF and skin type or initial
      MED. Dose-response curves were right shifted and parallel after phototherapy, and
      there was no significant difference in the maximum slope (P = 0.73). CONCLUSIONS:
      The photoadaptation caused by NB-UVB is considerably less than that reported for
      BB-UVB. The variation in photoadaptation between patients was not explained by
      skin type or baseline MED. Physical factors (such as tanning and epidermal
      thickening) are probably sufficient to account for photoadaptation, rather than
      downregulation of the inflammatory response. These data should help in the design
      of phototherapy protocols for NB-UVB to achieve optimal clearance of psoriasis.

PMID- 24125497
TI  - Combined dielectrophoresis-Raman setup for the classification of pathogens
      recovered from the urinary tract.
AB  - Rapid and effective methods of pathogen identifications are of major interest in
      clinical microbiological analysis to administer timely tailored antibiotic
      therapy. Raman spectroscopy as a label-free, culture-independent optical method
      is suitable to identify even single bacteria. However, the low bacteria
      concentration in body fluids makes it difficult to detect their characteristic
      molecular fingerprint directly in suspension. Therefore, in this study, Raman
      spectroscopy is combined with dielectrophoresis, which enables the direct
      translational manipulation of bacteria in suspensions with spatial nonuniform
      electrical fields so as to perform specific Raman spectroscopic characterization.
      A quadrupole electrode design is used to capture bacteria directly from fluids in
      well-defined microsized regions. With live/dead fluorescence viability staining,
      it is verified, that the bacteria survive this procedure for the relevant range
      of field strengths. The dielectrophoretic enrichment of bacteria allows for
      obtaining high quality Raman spectra in dilute suspensions with an integration
      time of only one second. As proof-of-principle study, the setup was tested with
      Escherichia coli and Enterococcus faecalis, two bacterial strains that are
      commonly encountered in urinary tract infections. Furthermore, to verify the
      potential for dealing with real world samples, pathogens from patients' urine
      have been analyzed. With the additional help of multivariate statistical
      analysis, a robust classification model could be built and allowed the
      classification of those two strains within a few minutes. In contrast, the
      standard microbiological diagnostics are based on very time-consuming cultivation
      tests. This setup holds the potential to reduce the crucial parameter diagnosis
      time by orders of magnitude. 

PMID- 24125496
TI  - In situ gelation for cell immobilization and culture in alginate foam scaffolds.
AB  - Essential cellular functions are often lost under culture in traditional two
      dimensional (2D) systems. Therefore, biologically more realistic three
      dimensional (3D) cell culture systems are needed that provide mechanical and
      biochemical cues which may otherwise be unavailable in 2D. For the present study,
      an alginate-based hydrogel system was used in which cells in an alginate solution
      were seeded onto dried alginate foams. A uniform distribution of NIH:3T3 and NHIK
      3025 cells entrapped within the foam was achieved by in situ gelation induced by
      calcium ions integrated in the foam. The seeding efficiency of the cells was
      about 100% for cells added in a seeding solution containing 0.1-1.0% alginate
      compared with 18% when seeded without alginate. The NHIK 3025 cells were allowed
      to proliferate and form multi-cellular structures inside the transparent gel that
      were later vital stained and evaluated by confocal microscopy. Gels were de
      gelled at different time points to isolate the multi-cellular structures and to
      determine the spheroid growth rate. It was also demonstrated that the mechanical
      properties of the gel could largely be varied through selection of type and
      concentration of the applied alginate and by immersing the already gelled disks
      in solutions providing additional gel-forming ions. Cells can efficiently be
      incorporated into the gel, and single cells and multi-cellular structures that
      may be formed inside can be retrieved without influencing cell viability or
      contaminating the sample with enzymes. The data show that the current system may
      overcome some limitations of current 3D scaffolds such as cell retrieval and in
      situ cell staining and imaging.

PMID- 24125499
TI  - Editorial for HTS revisited.

PMID- 24125498
TI  - Evaluation of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry for species identification of Acinetobacter strains isolated from
      blood cultures.
AB  - The clinical relevance of Acinetobacter species, other than A. baumannii, as
      human pathogens has not been sufficiently assessed owing to the insufficiency of
      simple phenotypic clinical diagnostic laboratory tests. Infections caused by
      these organisms have different impacts on clinical outcome and require different
      treatment and management approaches. It is therefore important to correctly
      identify Acinetobacter species. Matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF MS) has been introduced to identify a wide
      range of microorganisms in clinical laboratories, but only a few studies have
      examined its utility for identifying Acinetobacter species, particularly those of
      the non-Acinetobacter baumannii complex. We therefore evaluated MALDI-TOF MS for
      identification of Acinetobacter species by comparing it with sequence analysis of
      rpoB using 123 isolates of Acinetobacter species from blood. Of the isolates
      examined, we identified 106/123 (86.2%) to species, and 16/123 (13.0%) could only
      be identified as acinetobacters. The identity of one isolate could not be
      established. Of the 106 species identified, 89/106 (84.0%) were confirmed by rpoB
      sequence analysis, and 17/106 (16.0%) were discordant. These data indicate
      correct identification of 89/123 (72.4%) isolates. Surprisingly, all blood
      culture isolates were identified as 13 species of Acinetobacter, and the
      incidence of Acinetobacter pittii was unexpectedly high (42/123; 34.1%) and
      exceeded that of A. baumannii (22/123; 17.9%). Although the present
      identification rate using MALDI-TOF MS is not acceptable for species-level
      identification of Acinetobacter, further expansion of the database should remedy
      this situation.

PMID- 24125500
TI  - High-throughput hit finding and compound-profiling technologies for academic drug
      discovery.

PMID- 24125501
TI  - Evolution in thinking and processes?

PMID- 24125502
TI  - The impact of physical based methods screening and their delivery of better
      quality hits.

PMID- 24125503
TI  - Ion channel screening - automated patch clamp on the rise.

PMID- 24125504
TI  - Academic HTS: diverse portraits.

PMID- 24125505
TI  - Surface water withdrawals for Marcellus Shale gas development: performance of
      alternative regulatory approaches in the Upper Ohio River Basin.
AB  - Almost all of the water used for developing Marcellus Shale gas is withdrawn from
      surface water sources. State environmental and interstate water authorities take
      different approaches to managing these withdrawals. In the Upper Ohio River
      Basin, which covers the western third of Pennsylvania, the Pennsylvania
      Department of Environmental Protection requires that all water sources used for
      development have an approved water management plan. For surface water sources the
      plans stipulate the amount and timing of withdrawals from each source as a
      function of annual streamflow statistics. Neighboring regulatory authorities and
      some environmental groups now favor the use of monthly streamflow statistics to
      establish the conditions for water withdrawals. Our analysis indicates that,
      given the state of flow measurement data in the Upper Ohio River Basin, the
      annual streamflow statistics are more likely to prevent water withdrawals during
      the driest times of the year when aquatic ecosystems are most stressed, and to
      result in fewer and smaller occurrences of computed low-flow ecodeficits. 

PMID- 24125507
TI  - Adjustment, depression, and anxiety in mild cognitive impairment and early
      dementia: a systematic review of psychological intervention studies.
AB  - BACKGROUND: Many people with mild cognitive impairment (MCI) or early dementia
      suffer from concomitant depression and anxiety disorders, which in some cases,
      may be related difficulties adjusting to their diagnosis and associated cognitive
      problems. Successful adjustment and alleviation of depression and anxiety
      symptoms in these people is of critical importance for quality of life and may
      also help prevent, or delay, further cognitive decline. A variety of psychosocial
      intervention approaches has been trialed with this group. METHOD: The literature
      was systematically searched for community-based intervention studies that aim to
      improve depression, anxiety, or adjustment. Studies were included or excluded
      using a priori criteria. Once included, the quality of studies was evaluated
      using pre-set criteria. RESULTS: Seventeen of 925 studies identified through
      literature databases and manual searches met the inclusion criteria. Of these, 16
      were considered to be of at least "adequate quality." These included seven
      randomized controlled trials and eight pre-post studies. A diverse range of
      psychotherapeutic approaches, formats (individual or group), outcome measures,
      inclusion criteria, and cultural contexts were apparent, making comparisons
      between studies challenging. CONCLUSIONS: Several studies have demonstrated
      positive findings in the treatment of depression in older adults with early
      dementia using problem solving and modified cognitive behavior therapy (CBT)
      approaches. Amongst the large range of approaches trialed to improve adjustment
      and quality of life for patients with MCI and early dementia, some approaches,
      such as modified CBT, have shown promise. There is a need for replication studies
      using more rigorous methodology before clear clinical recommendations can be
      made.

PMID- 24125506
TI  - Structure-activity relationships of the N-terminus of calcitonin gene-related
      peptide: key roles of alanine-5 and threonine-6 in receptor activation.
AB  - BACKGROUND AND PURPOSE: The N-terminus of calcitonin gene-related peptide (CGRP)
      is important for receptor activation, especially the disulphide-bonded ring
      (residues 1-7). However, the roles of individual amino acids within this region
      have not been examined and so the molecular determinants of agonism are unknown.
      This study has examined the role of residues 1, 3-6 and 8-9, excluding Cys-2 and
      Cys-7. EXPERIMENTAL APPROACH: CGRP derivatives were substituted with either
      cysteine or alanine; further residues were introduced at position 6. Their
      affinity was measured by radioligand binding and their efficacy by measuring cAMP
      production in SK-N-MC cells and beta-arrestin 2 translocation in CHO-K1 cells at
      the CGRP receptor. KEY RESULTS: Substitution of Ala-5 by cysteine reduced
      affinity 270-fold and reduced efficacy for production of cAMP in SK-N-MCs.
      Potency at beta-arrestin translocation was reduced by ninefold. Substitution of
      Thr-6 by cysteine destroyed all measurable efficacy of both cAMP and beta
      arrestin responses; substitution with either alanine or serine impaired potency.
      Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10-fold
      reductions in potency at both responses. Similar observations were made at a
      second CGRP-activated receptor, the AMY(1(a)) receptor. CONCLUSIONS AND
      IMPLICATIONS: Ala-5 and Thr-6 are key determinants of agonist activity for CGRP.
      Ala-5 is also very important for receptor binding. Residues outside of the 1-7
      ring also contribute to agonist activity.

PMID- 24125508
TI  - Avibactam reverts the ceftazidime MIC90 of European Gram-negative bacterial
      clinical isolates to the epidemiological cut-off value.
AB  - OBJECTIVES: Ceftazidime-avibactam consists of the beta-lactam ceftazidime and the
      novel non-beta-lactam beta-lactamase inhibitor avibactam. The effect of avibactam
      on the ceftazidime MIC frequency distribution of Gram-negative European clinical
      isolates was observed and compared to European Committee for Antimicrobial
      Susceptibility Testing (EUCAST) MIC frequency distributions and epidemiological
      cut-off values (ECOFFs) listed for ceftazidime. METHODS: Ceftazidime and
      ceftazidime-avibactam MICs were determined using Clinical and Laboratory
      Standards Institute (CLSI) reference broth microdilution methods for Pseudomonas
      aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Enterobacter spp.,
      and Proteus mirabilis isolates collected from medical centres in Europe during
      2009. RESULTS: The MIC(90) values for ceftazidime and ceftazidime-avibactam
      against P. aeruginosa isolates from a 2009 European surveillance programme were
      >32 and 8 mg/l, respectively. That is, the presence of avibactam reverted the
      ceftazidime MIC(90) for P. aeruginosa to the ECOFF. Similarly, the MIC(90) values
      for ceftazidime against E. coli, Klebsiella spp., Serratia spp., and P. mirabilis
      were also reduced to the ECOFF by the presence of avibactam. Avibactam reduced
      the ceftazidime MIC(90) value against collected Enterobacter spp. to 1 mg/l (>32
      fold reduction). No ECOFF has been defined for Enterobacter spp. however, it is 1
      mg/l for Enterobacter aerogenes and Enterobacter cloacae. CONCLUSIONS: The
      presence of avibactam reverted the ceftazidime MIC(90) for Gram-negative bacteria
      to the ECOFF.

PMID- 24125509
TI  - Pancreatoscopy for pancreatic duct stones.

PMID- 24125511
TI  - Video demonstration of the rendezvous technique for the treatment of a malignant
      esophagorespiratory fistula.

PMID- 24125510
TI  - Salvage endoscopic submucosal dissection for the esophagus-localized recurrence
      of esophageal squamous cell cancer after definitive chemoradiotherapy.

PMID- 24125512
TI  - The effect of a novel drug-eluting plastic stent on biliary stone dissolution in
      an ex vivo bile perfusion model.
AB  - BACKGROUND: Temporary plastic stent insertion has been considered a safe and
      effective bridge therapy for difficult common bile duct (CBD) stones. Infusing
      chemicals to directly dissolve stones through the bile duct might also be
      effective. However, there are no studies on the efficacy of the combination of
      these 2 approaches. OBJECTIVE: To investigate the efficacy of a novel
      ethylenediaminetetraacetic acid (EDTA) and sodium cholate-eluting plastic stent
      on biliary stones. DESIGN: Ex vivo model by using different doses of active
      ingredient. SETTING AND INTERVENTIONS: An ex vivo bile duct model perfused with
      porcine bile was created. Stents coated with degradable membranes containing
      various concentrations of EDTA and sodium cholate were placed in the model with
      CBD stones. MAIN OUTCOME MEASUREMENTS: The change in the weight of stents and
      stones was measured every week during perfusion until the coated membranes were
      completely biodegraded. RESULTS: The time that the stents required to be fully
      degraded and the efficiency of stone dissolution were positively correlated with
      the percentage of EDTA and sodium cholate in the stent membrane. However, the 50%
      EDTA and sodium cholate stents achieved the greatest percentage of stone weight
      loss when the drugs were completely released. LIMITATIONS: Ex vivo study.
      CONCLUSIONS: The EDTA and sodium cholate-eluting plastic stent effectively
      dissolved CBD stones and has prospect in the therapy for patients with difficult
      CBD stones.

PMID- 24125513
TI  - Treatment of esophageal leaks, fistulae, and perforations with temporary stents:
      evaluation of efficacy, adverse events, and factors associated with successful
      outcomes.
AB  - BACKGROUND: Factors associated with successful endoscopic therapy with temporary
      stents for esophageal leaks, fistulae, and perforations (L/F/P) are not well
      known. OBJECTIVES: To evaluate the safety, efficacy, and outcomes of esophageal
      stenting in these patients and identify factors associated with successful
      closure. DESIGN: Retrospective. SETTING: Academic tertiary referral center.
      PATIENTS: All patients with attempted stent placement for esophageal L/F/P
      between January 2003 and May 2012. INTERVENTION: Esophageal stent placement and
      removal. MAIN OUTCOME MEASUREMENTS: Factors predictive of therapeutic success
      defined as complete closure after index stent removal (primary closure) or after
      further endoscopic stenting (secondary closure). RESULTS: Sixty-seven patients
      with 132 attempted stents for esophageal L/F/P were considered; 13 patients were
      excluded. Among the remaining 54 patients, 117 stents were placed for leaks (29
      patients; 64 stents), fistulae (15 patients; 36 stents), and perforations (10
      patients; 17 stents). Procedural technical success was achieved in all patients
      (100%). Primary closure was successful in 40 patients (74%) and secondary closure
      in an additional 5 (83% overall). On short-term (<3 months) follow-up, 27
      patients (50%) were asymptomatic, whereas 22 (41%) had technical adverse events,
      including stent migration in 15 patients (28%). Factors associated with
      successful primary closure include a shorter time between diagnosis of esophageal
      L/F/P and initial stent insertion (9.03 vs 22.54 days; P = .003), and a smaller
      luminal opening size (P = .002). LIMITATIONS: Retrospective, single-center study.
      CONCLUSIONS: Temporary stents are safe and effective in treating esophageal
      L/F/P. Defect opening size and time from diagnosis to stent placement appear to
      be candidate predictors for successful closure.

PMID- 24125514
TI  - Removal of small colorectal polyps in anticoagulated patients: a prospective
      randomized comparison of cold snare and conventional polypectomy.
AB  - BACKGROUND: The bleeding risk after cold snare polypectomy in anticoagulated
      patients is not known. OBJECTIVE: To compare the bleeding risk after cold snare
      polypectomy or conventional polypectomy for small colorectal polyps in
      anticoagulated patients. DESIGN: Prospective randomized controlled study.
      SETTING: Municipal hospital in Japan. INTERVENTIONS: Anticoagulated patients with
      colorectal polyps up to 10 mm in diameter were enrolled. Patients were randomized
      to polypectomy with either cold snare technique (Cold group) or conventional
      polypectomy (Conventional group) without discontinuation of warfarin. The primary
      outcome measure was delayed bleeding (ie, requiring endoscopic intervention
      within 2 weeks after polypectomy). Secondary outcome measures were immediate
      bleeding and retrieval rate of colorectal polyps. RESULTS: Seventy patients were
      randomized (159 polyps): Cold group (n = 35, 78 polyps) and Conventional group (n
      = 35; 81 polyps). The patients' demographic characteristics including
      international normalized ratio and the number, size, and shape of polyps removed
      were similar between the 2 techniques. Immediate bleeding during the procedure
      was more common with conventional polypectomy (23% [8/35]) compared with cold
      polypectomy (5.7% [2/35]) (P = .042). No delayed bleeding occurred in the Cold
      group, whereas 5 patients (14%) required endoscopic hemostasis in the
      Conventional group (P = .027). Complete polyp retrieval rates were identical (94%
      [73/78] vs 93% [75/81]). The presence of histologically demonstrated injured
      arteries in the submucosal layer with cold snare was significantly less than with
      conventional snare (22% vs 39%, P = .023). LIMITATION: Small sample size, single
      center study. CONCLUSIONS: Delayed bleeding requiring hemostasis occurred
      significantly less commonly after cold snare polypectomy than conventional
      polypectomy despite continuation of anticoagulants. Cold snare polypectomy is
      preferred for removal of small colorectal polyps in anticoagulated patients. (
      CLINICAL TRIAL REGISTRATION NUMBER: NCT 01553565.).

PMID- 24125515
TI  - EUS-guided drainage of a giant hemorrhagic pseudocyst by a through-the-scope
      esophageal metal stent.

PMID- 24125516
TI  - Extraluminal GI stromal tumor of the jejunum diagnosed by EUS at double-balloon
      endoscopy.

PMID- 24125517
TI  - Construction of ultrastable porphyrin Zr metal-organic frameworks through linker
      elimination.
AB  - A series of highly stable MOFs with 3-D nanochannels, namely PCN-224 (no metal,
      Ni, Co, Fe), have been assembled with six-connected Zr6 cluster and
      metalloporphyrins by a linker-elimination strategy. The PCN-224 series not only
      exhibits the highest BET surface area (2600 m(2)/g) among all the reported
      porphyrinic MOFs but also remains intact in pH = 0 to pH = 11 aqueous solution.
      Remarkably, PCN-224(Co) exhibits high catalytic activity for the CO2/propylene
      oxide coupling reaction and can be used as a recoverable heterogeneous catalyst.

PMID- 24125518
TI  - Impact of slow transit constipation on the outcome of laparoscopic ventral
      rectopexy for obstructed defaecation associated with high grade internal rectal
      prolapse.
AB  - AIM: Limited literature exists on whether slow colonic transit adversely
      influences the results of outlet obstruction surgery. We compared the functional
      results of laparoscopic ventral rectopexy (LVR) for obstructed defaecation
      secondary to high grade internal rectal prolapse in patients with normal and slow
      colonic transit. METHOD: Consecutive patients suffering from obstructed
      defaecation associated with an internal rectal prolapse, who underwent an LVR
      between 2007 and 2011, were identified from a prospective database. All patients
      underwent preoperative defaecating proctography, anorectal manometry and colonic
      transit studies. Symptoms were assessed preoperatively and at 12 months after
      operation using a standardized questionnaire incorporating the Patient Assessment
      of Constipation Symptoms (PAC-SYM) questionnaire, the Fecal Incontinence Severity
      Index (FISI), the Patient Assessment of Constipation Quality of Life (PAC-QOL)
      scale and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: In all,
      151 patients underwent LVR, 109 with normal and 42 with slow colonic transit.
      Preoperatively there was no significant difference between the two groups in age,
      sex, PAC-SYM score or FISI score. The PAC-SYM and FISI scores were significantly
      reduced in both groups at 12 months (P < 0.001). When comparing the change from
      baseline of PAC-SYM between patients with and without slow transit constipation,
      a significant difference was observed (P = 0.030) with changes of 58% and 40%.
      Quality of life (GIQLI and PAC-QOL) was equally improved in both groups. Quality
      of life improvement was less in patients with right colonic stasis. CONCLUSION:
      Slow colonic transit has no adverse impact on function and quality of life after
      LVR for obstructed defaecation due to high grade internal rectal prolapse.

PMID- 24125519
TI  - Paracoccidioides brasiliensis infection in domestic rabbits (Oryctolagus
      cuniculus).
AB  - The objective of this study was to evaluate the infection of domestic rabbits by
      Paracoccidioides brasiliensis. Initially two rabbits were experimentally infected
      with P. brasiliensis and the humoral immune response was evaluated by ELISA using
      gp43 as antigen. The two animals showed IgG response against gp43 although no
      signs of disease were observed. The seroepidemiological study was carried out in
      170 rabbits (free range n = 81 and caged n = 89) living in an endemic area for
      human paracoccidioidomycosis and a positivity of 27% was observed in the ELISA
      using gp43 as antigen. The free-range rabbits showed a significantly higher
      positivity (34.6-51.7%) than the caged animals (11.1%). Sentinel rabbits exposed
      to natural infection with P. brasiliensis were followed up for 6 months and a
      seroconversion rate of 83.3% was observed. This is the first report of
      paracoccidioidomycosis in rabbits and suggests that this species can be useful
      sentinels for P. brasiliensis presence in the environment. 

PMID- 24125522
TI  - Bendamustine for indolent non-Hodgkin lymphoma in the front-line or relapsed
      setting: a review of pharmacokinetics and clinical trial outcomes.
AB  - Bendamustine is an agent with mostly alkylating properties, which acts on
      dividing cells through multiple pathways. As an agent with little cross
      resistance with other chemotherapeutic agents, bendamustine has received approval
      for second-line use in relapsed/refractory indolent lymphomas. A growing body of
      data showing good efficacy and acceptable tolerability of bendamustine in first
      line use has led to recognition that this agent has an important role in this
      setting. This article outlines the pharmacology and clinical studies supporting
      the use of bendamustine and discusses the role of this agent in the first- and
      second-line treatment of indolent lymphomas. 

PMID- 24125520
TI  - Implementation of a children's hospital-wide central venous catheter insertion
      and maintenance bundle.
AB  - BACKGROUND: Central venous catheter-associated bloodstream infections in children
      are an increasingly recognized serious safety problem worldwide, but are often
      preventable. Central venous catheter bundles have proved effective to prevent
      such infections. Successful implementation requires changes in the hospital
      system as well as in healthcare professionals' behaviour. The aim of the study is
      to evaluate process and outcome of implementation of a state-of-the-art central
      venous catheter insertion and maintenance bundle in a large university children's
      hospital. METHODS/DESIGN: An interrupted time series design will be used; the
      study will encompass all children who need a central venous catheter. New state
      of-the-art central venous catheter bundles will be developed. The Pronovost-model
      will guide the implementation process. We developed a tailored multifaceted
      implementation strategy consisting of reminders, feedback, management support,
      local opinion leaders, and education. Primary outcome measure is the number of
      catheter-associated infections per 1000 line-days. The process outcome is degree
      of adherence to use of these central venous catheter bundles is the secondary
      outcome. A cost-effectiveness analysis is part of the study. Outcomes will be
      monitored during three periods: baseline, pre-intervention, and post-intervention
      for over 48 months. DISCUSSION: This model-based implementation strategy will
      reveal the challenges of implementing a hospital-wide safety program. This work
      will add to the body of knowledge in the field of implementation. We postulate
      that healthcare workers' willingness to shift from providing habitual care to
      state-of-the-art care may reflect the need for consistent care improvement. Trial
      registration: Dutch trials registry, trial # 3635. TRIAL REGISTRATION: Dutch
      trials registry (http://www.trialregister.nl), trial # 3635.

PMID- 24125523
TI  - Thrombosis in pediatric cancer: identifying the risk factors to improve care.
AB  - Cancer-associated thromboembolism (TE) is now a frequent complication in
      children. The reported prevalence varies from up to 16% of symptomatic to 40% of
      asymptomatic TE in children with cancer. Compared to the general pediatric
      population, children with cancer who develop TE have an increased risk of death,
      TE recurrence, TE-related morbidity and higher potential for utilization of
      health care resources. TE is preventable with anticoagulation therapy. With over
      80% cure rates of childhood cancer, strategies for prevention as well as for
      early diagnosis and optimal treatment of TE in children with cancer are of major
      importance. An understanding of the risk factors predisposing children with
      cancer for development of TE will facilitate development of preventive and
      therapeutic strategies. 

PMID- 24125526
TI  - Flavonoids with alpha-glucosidase inhibitory activities and their contents in the
      leaves of Morus atropurpurea.
AB  - BACKGROUND: This study aims to isolate the alpha-glucosidase inhibitory compounds
      from mulberry leaves (Morus atropurpurea Roxb., Moraceae) and to develop an
      analytical method for quantification of the compounds. METHODS: Four flavonoids,
      rutin (1), isoquercetin (2), kaempferol-3-O-rutinoside (3) and astragalin (4),
      were isolated by column chromatography from mulberry leaf water extracts (MWE).
      The alpha-glucosidase inhibitory activities of MWE and the four isolated
      compounds were evaluated by a microplate-based in vitro assay. The content of the
      isolated flavonoids in M. atropurpurea leaves purchased from different local
      herbal stores or collected in different locations was determined by high
      performance liquid chromatography. RESULTS: The four flavonoids (1-4) showed
      alpha-glucosidase inhibitory activities, with rutin (1) and astragalin (4)
      showing high alpha-glucosidase inhibitory activities (IC50 values of 13.19 +/-
      1.10 and 15.82 +/- 1.11 MUM, respectively). The total contents of the four
      flavonoids were different among eight samples examined, ranging from 4.34 mg/g to
      0.53 mg/g. CONCLUSIONS: The four flavonoids in M. atropurpurea leaves could
      inhibit alpha-glucosidase activity.

PMID- 24125525
TI  - De novo assembly and characterization of leaf transcriptome for the development
      of functional molecular markers of the extremophile multipurpose tree species
      Prosopis alba.
AB  - BACKGROUND: Prosopis alba (Fabaceae) is an important native tree adapted to arid
      and semiarid regions of north-western Argentina which is of great value as
      multipurpose species. Despite its importance, the genomic resources currently
      available for the entire Prosopis genus are still limited. Here we describe the
      development of a leaf transcriptome and the identification of new molecular
      markers that could support functional genetic studies in natural and domesticated
      populations of this genus. RESULTS: Next generation DNA pyrosequencing technology
      applied to P. alba transcripts produced a total of 1,103,231 raw reads with an
      average length of 421 bp. De novo assembling generated a set of 15,814 isotigs
      and 71,101 non-assembled sequences (singletons) with an average of 991 bp and 288
      bp respectively. A total of 39,000 unique singletons were identified after
      clustering natural and artificial duplicates from pyrosequencing reads.Regarding
      the non-redundant sequences or unigenes, 22,095 out of 54,814 were successfully
      annotated with Gene Ontology terms. Moreover, simple sequence repeats (SSRs) and
      single nucleotide polymorphisms (SNPs) were searched, resulting in 5,992 and
      6,236 markers, respectively, throughout the genome. For the validation of the the
      predicted SSR markers, a subset of 87 SSRs selected through functional annotation
      evidence was successfully amplified from six DNA samples of seedlings. From this
      analysis, 11 of these 87 SSRs were identified as polymorphic. Additionally,
      another set of 123 nuclear polymorphic SSRs were determined in silico, of which
      50% have the probability of being effectively polymorphic. CONCLUSIONS: This
      study generated a successful global analysis of the P. alba leaf transcriptome
      after bioinformatic and wet laboratory validations of RNA-Seq data.The limited
      set of molecular markers currently available will be significantly increased with
      the thousands of new markers that were identified in this study. This information
      will strongly contribute to genomics resources for P. alba functional analysis
      and genetics. Finally, it will also potentially contribute to the development of
      population-based genome studies in the genera.

PMID- 24125527
TI  - Cyclic mechanical loading enables solute transport and oxygen supply in bone
      healing: an in vitro investigation.
AB  - Bone healing is a complex process with an increased metabolic activity and
      consequently high demand for oxygen. In the hematoma phase, inflammatory cells
      and mesenchymal stromal cells (MSCs) are initially cut off from direct
      nutritional supply via blood vessels. Cyclic mechanical loading that occurs, for
      example, during walking is expected to have an impact on the biophysical
      environment of the cells but meaningful quantitative experimental data are still
      missing. In this study, the hypothesis that cyclic mechanical loading within a
      physiological range significantly contributes to oxygen transport into the
      fracture hematoma was investigated by an in vitro approach. MSCs were embedded in
      a fibrin matrix to mimic the hematoma phase during bone healing. Construct
      geometry, culture conditions, and parameters of mechanical loading in a
      bioreactor system were chosen to resemble the in vivo situation based on data
      from human studies and a well-characterized large animal model. Oxygen tension
      was measured before and after mechanical loading intervals by a chemical optical
      microsensor. The increase in oxygen tension at the center of the constructs was
      significant and depended on loading time with maximal values of 9.9%+/-5.1%,
      14.8%+/-4.9%, and 25.3%+/-7.2% of normal atmospheric oxygen tension for 5, 15,
      and 30 min of cyclic loading respectively. Histological staining of hypoxic cells
      after 48 h of incubation confirmed sensor measurements by showing an increased
      number of normoxic cells with intermittent cyclic compression compared with
      unloaded controls. The present study demonstrates that moderate cyclic mechanical
      loading leads to an increased oxygen transport and thus to substantially enhanced
      supply conditions for cells entrapped in the hematoma. This link between
      mechanical conditions and nutrition supply in the early regenerative phases could
      be employed to improve the environmental conditions for cell metabolism and
      consequently prevent necrosis.

PMID- 24125528
TI  - Optimization of the magnetoelectric response of poly(vinylidene
      fluoride)/epoxy/Vitrovac laminates.
AB  - The effect of the bonding layer type and piezoelectric layer thickness on the
      magnetoelectric (ME) response of layered poly(vinylidene fluoride)
      (PVDF)/epoxy/Vitrovac composites is reported. Three distinct epoxy types were
      tested, commercially known as M-Bond, Devcon, and Stycast. The main differences
      among them are their different mechanical characteristics, in particular the
      value of the Young modulus, and the coupling with the polymer and Vitrovac
      (Fe39Ni39Mo4Si6B12) layers of the laminate. The laminated composites prepared
      with M-Bond epoxy exhibit the highest ME coupling. Experimental results also show
      that the ME response increases with increasing PVDF thickness, the highest ME
      response of 53 V.cm(-1).Oe(-1) being obtained for a 110 MUm thick PVDF/M-Bond
      epoxy/Vitrovac laminate. The behavior of the ME laminates with increasing
      temperatures up to 90  degrees C shows a decrease of more than 80% in the ME
      response of the laminate, explained by the deteriorated coupling between the
      different layers. A two-dimensional numerical model of the ME laminate composite
      based on the finite element method was used to evaluate the experimental results.
      A comparison between numerical and experimental data allows us to select the
      appropriate epoxy and to optimize the piezoelectric PVDF layer width to maximize
      the induced magnetoelectric voltage. The obtained results show the critical role
      of the bonding layer and piezoelectric layer thickness in the ME performance of
      laminate composites. 

PMID- 24125531
TI  - Metagenomic profiles of antibiotic resistance genes (ARGs) between human impacted
      estuary and deep ocean sediments.
AB  - Knowledge of the origins and dissemination of antibiotic resistance genes (ARGs)
      is essential for understanding modern resistomes in the environment. The
      mechanisms of the dissemination of ARGs can be revealed through comparative
      studies on the metagenomic profiling of ARGs between relatively pristine and
      human-impacted environments. The deep ocean bed of the South China Sea (SCS) is
      considered to be largely devoid of anthropogenic impacts, while the Pearl River
      Estuary (PRE) in south China has been highly impacted by intensive human
      activities. Commonly used antibiotics (sulfamethazine, norfloxacin, ofloxacin,
      tetracycline, and erythromycin) have been detected through chemical analysis in
      the PRE sediments, but not in the SCS sediments. In the relatively pristine SCS
      sediments, the most prevalent and abundant ARGs are those related to resistance
      to macrolides and polypeptides, with efflux pumps as the predominant mechanism.
      In the contaminated PRE sediments, the typical ARG profiles suggest a prevailing
      resistance to antibiotics commonly used in human health and animal farming
      (including sulfonamides, fluoroquinolones, and aminoglycosides), and higher
      diversity in both genotype and resistance mechanism than those in the SCS. In
      particular, antibiotic inactivation significantly contributed to the resistance
      to aminoglycosides, beta-lactams, and macrolides observed in the PRE sediments.
      There was a significant correlation in the levels of abundance of ARGs and those
      of mobile genetic elements (including integrons and plasmids), which serve as
      carriers in the dissemination of ARGs in the aquatic environment. The metagenomic
      results from the current study support the view that ARGs naturally originate in
      pristine environments, while human activities accelerate the dissemination of
      ARGs so that microbes would be able to tolerate selective environmental stress in
      response to anthropogenic impacts. 

PMID- 24125529
TI  - Caenorhabditis elegans in Chinese medicinal studies: making the case for aging
      and neurodegeneration.
AB  - Aging is a progressive process with degenerative changes of various tissues and
      organs. As a classic model organism in genetics and neurobiology, Caenorhabditis
      elegans is also a powerful system in aging and behavioral studies and can be used
      at both the molecular and organismal levels to evaluate potential therapeutics
      for age-related neurodegeneration, owing to its short life span, relative
      simplicity, and high degree of experimental tractability as well as significant
      conservation of disease genes and signaling pathways with humans. We attempt here
      to summarize the use of C. elegans models in exploring traditional Chinese
      medicine for potential remedies against aging and neurodegeneration.

PMID- 24125532
TI  - Leap behavior of ultrasonic standing waves in the liquids.
AB  - The generation and behavior of ultrasonic standing waves was modeled using the
      light cut method for transparent fluid. The oscillations of the fluid surface in
      initial moment of switching on ultrasound and appearance of standing wave channel
      were observed. The effect of continuous fluid depth decrease and increase on the
      behavior of ultrasonic standing wave channel was studied. The ultrasonic standing
      wave channel floated in the liquid between of the crucible bottom and fluid
      surface and discretely changed its height by half ultrasonic wavelength with the
      decrease or increase of the liquid level. This channel had the behavior of a
      "quasi solid state" and damped of convection. 

PMID- 24125533
TI  - Measurements of ultrasound velocity and attenuation in numerical anisotropic
      porous media compared to Biot's and multiple scattering models.
AB  - This article quantitatively investigates ultrasound propagation in numerical
      anisotropic porous media with finite-difference simulations in 3D. The
      propagation media consist of clusters of ellipsoidal scatterers randomly
      distributed in water, mimicking the anisotropic structure of cancellous bone.
      Velocities and attenuation coefficients of the ensemble-averaged transmitted wave
      (also known as the coherent wave) are measured in various configurations. As in
      real cancellous bone, one or two longitudinal modes emerge, depending on the
      micro-structure. The results are confronted with two standard theoretical
      approaches: Biot's theory, usually invoked in porous media, and the Independent
      Scattering Approximation (ISA), a classical first-order approach of multiple
      scattering theory. On the one hand, when only one longitudinal wave is observed,
      it is found that at porosities higher than 90% the ISA successfully predicts the
      attenuation coefficient (unlike Biot's theory), as well as the existence of
      negative dispersion. On the other hand, the ISA is not well suited to study two
      wave propagation, unlike Biot's model, at least as far as wave speeds are
      concerned. No free fitting parameters were used for the application of Biot's
      theory. Finally we investigate the phase-shift between waves in the fluid and the
      solid structure, and compare them to Biot's predictions of in-phase and out-of
      phase motions. 

PMID- 24125534
TI  - 13C NMR spectroscopy for the differentiation of enantiomers using chiral
      solvating agents.
AB  - The utility of (13)C NMR spectroscopy for the differentiation of enantiomers
      using chiral solvating agents (CSA) is stated. Three examples involving the
      enantiodifferentiation of a drug, a metabolite and a reactant in aqueous and
      organic solutions have been chosen to show it. The intrinsic high dispersion of
      (13)C nucleus, as well as the singlet nature of the signals in standard
      experiments makes (13)C NMR experiments a powerful alternative or complement to
      (1)H NMR experiments; specially, when studying pure compounds with complex proton
      spectra or mixtures of compounds, as in chiral metabonomics, where severe
      overlapping exists in proton spectrum. To evaluate and compare the quality of the
      enantioresolution of a NMR signal we introduce the enantiodifferentiation
      quotient, E, that considers the complexity of (1)H multiplets (and in general the
      width) of the original signal. It has been observed that the error in the
      measurement of the enantiomeric molar ratio can be related to the E value. The
      sensitivity and experimental time of a wide range of chiral analyte
      concentrations were also assessed. 

PMID- 24125535
TI  - De novo mutation in the KCNQ1 gene causal to Jervell and Lange-Nielsen syndrome.
AB  - Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive disorder,
      clinically characterized by severe cardiac arrhythmias [due to prolonged QTc
      interval in electrocardiogram (ECG)] and bilateral sensory neural deafness.
      Molecular defects causal to JLNS are either homozygous or compound heterozygous
      mutations, predominantly in the KCNQ1 gene and occasionally in the KCNE1 gene. As
      the molecular defect is bi-allelic, JLNS patients inherit one pathogenic mutation
      causal to the disorder from each parent. In this report, we show for the first
      time that such a disorder could also occur due to a spontaneous de novo mutation
      in the affected individual, not inherited from the parent, which makes this case
      unique unlike the previously reported JLNS cases. 

PMID- 24125536
TI  - Impact of subclinical haemorrhage on the pituitary gland in patients with
      pituitary adenomas.
AB  - OBJECTIVE: Advanced magnetic resonance imaging (MRI) and optical instruments for
      surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas;
      however, the effects of subclinical haemorrhage on pituitary glands remain
      unclear. We sought to clarify the pituitary function in patients with subclinical
      pituitary adenoma haemorrhage (SPAH). DESIGN/PATIENTS: Between January 2006 and
      December 2012, we retrospectively reviewed 328 consecutive patients who underwent
      surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage
      based on both 3 tesla MRI and operative findings, with no clinical symptoms of
      acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre-
      and postoperative provocative tests was investigated in patients categorized into
      three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical
      apoplexy. MEASUREMENTS: The main outcome measure was the incidence of pituitary
      dysfunction. RESULTS: The overall incidence of nonapoplectic adenomas, adenomas
      with SPAH and adenomas with clinical apoplexy was 82.3%, 14.3% and 3.4%,
      respectively. Clinical pituitary apoplexy frequently occurred in male patients
      with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly,
      the incidence of SPAH was significantly higher in the patients with prolactinoma
      (P = 0.0260), including those with relatively small adenomas (P = 0.0007). No
      medications, such as dopamine agonists or somatostatin analogues, were observed
      to affect the occurrence of SPAH. No deterioration of the pituitary function was
      observed in the SPAH patients in comparison with the patients with nonapoplectic
      adenoma, and the size of the haematoma occupying the pituitary adenoma did not
      exhibit any relationships with the deterioration of the pituitary function.
      Furthermore, SPAH caused no deterioration of the pituitary function after a
      surgery based on the postoperative provocation tests. CONCLUSIONS: Subclinical
      pituitary adenoma haemorrhage does not cause any added dysfunction in pituitary
      glands. Signs of haemorrhage in pituitary adenomas do not necessitate immediate
      tumour decompression surgery, if there are no symptoms of acute haemorrhage.

PMID- 24125537
TI  - Reconstruction of a neurocutaneous defect of the proximal phalanx with a
      heterodigital arterialised nerve pedicle flap.
AB  - BACKGROUND: Complex digital injuries involving soft-tissue loss and digital nerve
      defect pose a challenging problem for hand surgeons. The purpose of this study
      was to evaluate the efficacy of transferring the heterodigital arterialised nerve
      pedicle flap for reconstructing the digital neurocutaneous defects and to compare
      the results with those of transferring the cross-finger flap and secondary nerve
      grafting. METHODS: From March 2008 to September 2011, the nerve pedicle flap was
      used in 12 patients who had a combination of soft-tissue and digital nerve
      defects. The injured fingers included four index, four long, three ring and one
      little finger. The mean size of the soft-tissue losses was 2.4*1.9 cm (range,
      2.3*1.3 to 3.2*2.0 cm). The mean flap size was 2.6*2.1 cm (range, 2.5*1.5 to
      3.4*2.2 cm). The length of the nerve defects ranged from 1.5 to 3.8 cm (mean, 2.8
      cm). The nerve defect was reconstructed with transfer of the digital nerve dorsal
      branch. For comparison, we collected a series of 24 patients with similar defects
      treated with the cross-finger flap and secondary free nerve grafting. RESULTS:
      Significant differences were found between the two groups in static two-point
      discrimination (p<.01) and pain (p=.03) in the reconstructed finger. In
      comparison, the study group presented better discriminatory sensation on the
      finger pulp and lower incidence of pain sensibility in the injured finger. There
      was no significant difference in cold intolerance and Semmes-Weinstein
      monofilament. In the study group, the total active motion of the donor fingers
      was similar to that of the opposite hands. CONCLUSIONS: The heterodigital
      arterialised nerve pedicle flap is useful and reliable for reconstructing the
      neurocutaneous defects in the proximal phalanx. Comparable sensory recovery and
      lower pain incidence can be achieved using our nerve pedicle flap instead of
      conventional nerve grafting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 24125538
TI  - Assessment of medical resource utilization for Taiwanese children hospitalized
      for intracranial injuries.
AB  - BACKGROUND: Compared to adults, children and adolescents are at greater risk for
      traumatic brain injury (TBI), with increased severity and prolonged recovery when
      compared to adults. It is a challenge to provide care for those children who are
      at risk for complications of TBI under health care resource constraints. AIM: To
      investigate hospitalization among children with intracranial injuries in terms of
      incidence and factors related to length of stay (LOS) and medical cost. METHODS:
      Data from the National Health Insurance Research Database from 2007-2009 were
      used. In total 8632 children aged <=18 years with acute traumatic intracranial
      injuries caused by accidents were discharged from hospitals in Taiwan. The
      associations between patient and hospital covariates (e.g., age, gender,
      accreditation level of hospital, surgical intervention, and number of comorbid
      conditions) and log-transferred hospitalization cost and length of stay (LOS)
      were examined with multivariable regression analysis and mediation analyses.
      RESULTS: The incidence rate of hospitalization for acute intracranial injury was
      63.3/100,000 per year. Motor vehicle crashes and falls accounted for 63.5% and
      23.8% of intracranial injuries, respectively. The mean LOS for children was 5.0
      days (median, 3 days), incurring a mean direct medical cost of $US 916.70
      (median, $356.2). Boy sustained more injury (64.1%) and greater medicals cost
      ($965) occurred in boys. Patients with subarachnoid subdural and extradural
      haemorrhage tended to have a longer LOS and incur greater medical costs. Surgical
      intervention and type of healthcare institution were also significant predictors
      for medical costs. Additionally, LOS was the dominant mediator for the
      relationship between predictor and medical cost. CONCLUSIONS: Acute intracranial
      injuries among children incur a substantial health care burden. Therefore, health
      authorities need to optimally allocate medical resources in care.

PMID- 24125541
TI  - Stem cells.

PMID- 24125542
TI  - Viral and non-viral gene delivery and its role in pluripotent stem cell
      engineering.

PMID- 24125539
TI  - Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection
      against myocardial ischemia/reperfusion injury in the rat.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its mimetics reduce infarct size
      in the setting of acute myocardial ischemia/reperfusion (I/R) injury. However,
      the short serum half-life of GLP-1 and its mimetics may limit their therapeutic
      use in acute myocardial ischemia. Domain antibodies to serum albumin (AlbudAbs)
      have been developed to extend the serum half-life of short lived therapeutic
      proteins, peptides and small molecules. In this study, we compared the effect of
      a long acting GLP-1 agonist, DPP-IV resistant GLP-1 (7-36, A8G) fused to an
      AlbudAb (GAlbudAb), with the effect of the GLP-1 mimetic, exendin-4 (short half
      life GLP-1 agonist) on infarct size following acute myocardial I/R injury.
      METHODS: Male Sprague-Dawley rats (8-week-old) were treated with vehicle,
      GAlbudAb or exendin-4. Myocardial ischemia was induced 2 h following the final
      dose for GAlbudAb and 30 min post the final dose for exendin-4. In a subgroup of
      animals, the final dose of exendin-4 was administered (1 MUg/kg, SC, bid for 2
      days) 6 h prior to myocardial ischemia when plasma exendin-4 was at its minimum
      concentration (C(min)). Myocardial infarct size, area at risk and cardiac
      function were determined 24 h after myocardial I/R injury. RESULTS: GAlbudAb and
      exendin-4 significantly reduced myocardial infarct size by 28% and 23%
      respectively, compared to vehicle (both p < 0.01 vs. vehicle) after I/R injury.
      Moreover, both GAlbudAb and exendin-4 markedly improved post-ischemic cardiac
      contractile function. Body weight loss and reduced food intake consistent with
      the activation of GLP-1 receptors was observed in all treatment groups. However,
      exendin-4 failed to reduce infarct size when administered 6 h prior to myocardial
      ischemia, suggesting continuous activation of the GLP-1 receptors is needed for
      cardioprotection. CONCLUSIONS: Cardioprotection provided by GAlbudAb, a long
      acting GLP-1 mimetic, following myocardial I/R injury was comparable in
      magnitude, but more sustained in duration than that produced by short-acting
      exendin-4. Very low plasma concentrations of exendin-4 failed to protect the
      heart from myocardial I/R injury, suggesting that sustained GLP-1 receptor
      activation plays an important role in providing cardioprotection in the setting
      of acute myocardial I/R injury. Long-acting GLP-1 agonists such as GAlbudAb may
      warrant additional evaluation as novel therapeutic agents to reduce myocardial
      I/R injury during acute coronary syndrome.

PMID- 24125540
TI  - Proteasome inhibitors: possible novel therapeutic strategy for ischemia
      reperfusion injury?
AB  - INTRODUCTION: The ubiquitin-proteasome system (UPS) is responsible for the
      degradation of misfolded or damaged proteins, regulating inflammatory processes
      and cell cycle progression. The aim of this article is to summarize the currently
      available data regarding the possible utility of proteasome inhibitors (PIs) in
      the treatment of ischemia-reperfusion injury (IRI). AREAS COVERED: Data were
      reviewed from the published literature using the Medline database. The effect of
      PIs on IRI is dependent on the dosage, time of administration (prior to or post
      IRI induction), the affected organ, and the experimental model used. Undoubtedly,
      in most cases PIs' application resulted in attenuated IRI, although it was
      uniformly shown that inhibition of the UPS prior to ischemic preconditioning
      (IPC) abolished the protective effect of IPC in IRI. Mechanism of action involves
      several pathways, including nuclear factor kappa-B (NF-kappaB) inactivation,
      antineutrophil action, decreased intracellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) expression, and the cytoprotective
      proteins eNOS, heme oxigenase 1 and hsp70 up-regulation. EXPERT OPINION: Current
      data are limited, but appear promising with regard to PI consideration as an
      effective future therapeutic strategy for IRI. Nevertheless, further
      investigation is required in terms of safety and validation of the appropriate
      for each agent dosage, in order to establish their possible contribution in human
      IRI.

PMID- 24125543
TI  - Stem cell reprogramming: generation of patient-specific stem cells by somatic
      cell nuclear reprogramming.

PMID- 24125544
TI  - Advances and perspectives in human and mouse embryonic stem cell bioprocessing.

PMID- 24125545
TI  - Derivation, maintenance and cryostorage of human embryonic stem cells.

PMID- 24125547
TI  - Livers cells derived from human embryonic stem cells.

PMID- 24125546
TI  - Epigenetic remodeling and stem cells.

PMID- 24125549
TI  - Size dependence of the structure of organic aerosol.
AB  - The effects of aerosol particles on heterogeneous atmospheric chemistry and
      climate are determined in part by the internal arrangement of compounds within
      the particles. We have used cryo-transmission electron microscopy to investigate
      the phase separation behavior of model organic aerosol composed of ammonium
      sulfate internally mixed with succinic or pimelic acid. We have found that no
      particle with a diameter <170 nm for succinic acid and 270 nm for pimelic acid is
      phase separated. Larger particles adopt a phase separated, partially engulfed
      structure. We therefore demonstrate that phase separation of aerosol particles is
      dependent on particle size and discuss implications for aerosol-climate
      interactions. 

PMID- 24125548
TI  - Epidemiology and predictive factors for early and late mortality in Candida
      bloodstream infections: a population-based surveillance in Spain.
AB  - A prospective, multicentre, population-based surveillance programme for Candida
      bloodstream infections was implemented in five metropolitan areas of Spain to
      determine its incidence and the prevalence of antifungal resistance, and to
      identify predictors of death. Between May 2010 and April 2011, Candida isolates
      were centralized to a reference laboratory for species identification by DNA
      sequencing and for susceptibility testing by EUCAST reference procedure.
      Prognostic factors associated with early (0-7 days) and late (8-30 days) death
      were analysed using logistic regression modelling. We detected 773 episodes:
      annual incidence of 8.1 cases/100 000 inhabitants, 0.89/1000 admissions and
      1.36/10 000 patient-days. Highest incidence was found in infants younger than 1
      year (96.4/100 000 inhabitants). Candida albicans was the predominant species
      (45.4%), followed by Candida parapsilosis (24.9%), Candida glabrata (13.4%) and
      Candida tropicalis (7.7%). Overall, 79% of Candida isolates were susceptible to
      fluconazole. Cumulative mortality at 7 and 30 days after the first episode of
      candidaemia was 12.8% and 30.6%, respectively. Multivariate analysis showed that
      therapeutic measures within the first 48 h may improve early mortality:
      antifungal treatment (OR 0.51, 95% CI 0.27-0.95) and central venous catheter
      removal (OR 0.43, 95% CI 0.21-0.87). Predictors of late death included host
      factors (e.g. patients' comorbid status and signs of organ dysfunction), primary
      source (OR 1.63, 95% CI 1.03-2.61), and severe sepsis or septic shock (OR 1.77,
      95% CI 1.05-3.00). In Spain, the proportion of Candida isolates non-susceptible
      to fluconazole is higher than in previous reports. Early mortality may be
      improved with strict adherence to guidelines.

PMID- 24125550
TI  - Maternal and perinatal consequences of antepartum haemorrhage of unknown origin.
AB  - OBJECTIVE: To explore the risk of adverse maternal and perinatal outcomes in
      women with antepartum bleeding of unknown origin (ABUO). DESIGN: Cohort study
      based on data extracted from the Aberdeen Maternity and Neonatal Databank.
      Exposure was antepartum haemorrhage occurring after the first trimester not
      attributable to placenta praevia or placental abruption. SETTING: Aberdeen
      Maternity Hospital, Aberdeen, Scotland, UK. POPULATION: All primigravidae
      delivering between 1976 and 2010. METHODS: Data were analysed using univariate
      and multivariate statistical methods. MAIN OUTCOME MEASURES: Pre-eclampsia,
      induced labour, mode of delivery, preterm delivery, postpartum haemorrhage,
      admission to neonatal unit, perinatal death. RESULTS: Between 1976 and 2010,
      there were 7517 women with ABUO and 68,423 women without ABUO in the cohort.
      Women with ABUO were more likely to be non-smokers, belong to a lower social
      class, and have a higher body mass index. ABUO was a significant risk factor for
      induced labour (adjusted odds ratio, aOR, 1.23; 95% CI 1.16-1.31), preterm
      delivery at <37 weeks of gestation (aOR 2.30; 95% CI 2.11-2.50), and postpartum
      haemorrhage (aOR 1.15; 95% CI 1.06-1.25). There was no significant association
      detected with pre-eclampsia (aOR 0.93; 95% CI 0.83-1.05). Whereas there was an
      increased risk of low birthweight (aOR 0.90; 95% CI 0.79-1.03) and stillbirth
      (aOR 0.92; 95% CI 0.66-1.30) with ABUO on univariate analysis, once adjusted for
      confounding factors this risk was non-significant. CONCLUSION: Pregnancies
      complicated by ABUO are at a greater risk of preterm delivery and induced labour.
      There was no increase seen in perinatal mortality after adjusting for preterm
      birth.

PMID- 24125551
TI  - Mesenchymal stem cells systemically injected into femoral marrow of dogs home to
      mandibular defects to enhance new bone formation.
AB  - Musculoskeletal diseases cost the U.S. $849 billion annually. To date, there has
      been no proof that remote long bone mesenchymal stem cells (BMSC) can home to
      craniofacial defects for bone regeneration. There has been no report that
      systemic BMSC injection can increase new bone formation in large animals. The
      objectives of this study were to use a sex-mismatched canine model for systemic
      BMSC injection and homing to mandibular defects and to investigate appendicular
      BMSC migration to craniofacial defects to increase new bone formation. Male
      beagle dog BMSC were injected into the femoral marrow cavity of female dogs upon
      which mandibular defects were created. The dogs were sacrificed at 6 weeks. Cells
      with Y chromosome markers were detected in defects of female dogs with systemic
      male BMSC injection, indicating the homing of the transplanted BMSC from femoral
      marrow to the mandibular defect. New bone formation in dogs with systemic BMSC
      injection was 20-40% higher than control without BMSC injection (p<0.05).
      Mineralized new bone percentage was increased by 20-40% due to systemic BMSC
      injection (p<0.05). In conclusion, this study proved that (1) allogeneic BMSC
      injected into long bone marrow are capable of homing to both appendicular and
      craniofacial bone in large animals and (2) systemically injected BMSC can
      significantly increase new bone formation in dog's mandibular defects. These
      results may help advance the understanding of stem cell homing and present a
      therapy to enhance bone repair, which may have a wide applicability to the
      regenerative medicine field.

PMID- 24125552
TI  - Alleles of the homologous recombination gene, RAD59, identify multiple responses
      to disrupted DNA replication in Saccharomyces cerevisiae.
AB  - BACKGROUND: In Saccharomyces cerevisiae, Rad59 is required for multiple
      homologous recombination mechanisms and viability in DNA replication-defective
      rad27 mutant cells. Recently, four rad59 missense alleles were found to have
      distinct effects on homologous recombination that are consistent with separation
      of-function mutations. The rad59-K166A allele alters an amino acid in a conserved
      alpha-helical domain, and, like the rad59 null allele diminishes association of
      Rad52 with double-strand breaks. The rad59-K174A and rad59-F180A alleles alter
      amino acids in the same domain and have genetically similar effects on homologous
      recombination. The rad59-Y92A allele alters a conserved amino acid in a separate
      domain, has genetically distinct effects on homologous recombination, and does
      not diminish association of Rad52 with double-strand breaks. RESULTS: In this
      study, rad59 mutant strains were crossed with a rad27 null mutant to examine the
      effects of the rad59 alleles on the link between viability, growth and the
      stimulation of homologous recombination in replication-defective cells. Like the
      rad59 null allele, rad59-K166A was synthetically lethal in combination with
      rad27. The rad59-K174A and rad59-F180A alleles were not synthetically lethal in
      combination with rad27, had effects on growth that coincided with decreased
      ectopic gene conversion, but did not affect mutation, unequal sister-chromatid
      recombination, or loss of heterozygosity. The rad59-Y92A allele was not
      synthetically lethal when combined with rad27, stimulated ectopic gene conversion
      and heteroallelic recombination independently from rad27, and was mutually
      epistatic with srs2. Unlike rad27, the stimulatory effect of rad59-Y92A on
      homologous recombination was not accompanied by effects on growth rate, cell
      cycle distribution, mutation, unequal sister-chromatid recombination, or loss of
      heterozygosity. CONCLUSIONS: The synthetic lethality conferred by rad59 null and
      rad59-K166A alleles correlates with their inhibitory effect on association of
      Rad52 with double-strand breaks, suggesting that this may be essential for
      rescuing replication lesions in rad27 mutant cells. The rad59-K174A and rad59
      F180A alleles may fractionally reduce this same function, which proportionally
      reduced repair of replication lesions by homologous recombination and growth
      rate. In contrast, rad59-Y92A stimulates homologous recombination, perhaps by
      affecting association of replication lesions with the Rad51 recombinase. This
      suggests that Rad59 influences the rescue of replication lesions by multiple
      recombination factors.

PMID- 24125553
TI  - Factorial validity of the Center for Epidemiologic Studies Depression Scale short
      form in older population in China.
AB  - BACKGROUND: The objective of this study was to explore the factor structure of a
      shortened ten-item Center for Epidemiologic Studies Depression Scale (CES-D 10)
      used in a national survey in China. METHODS: This secondary research is based on
      the wave I (2011) of the China Health Aging Retirement and Longevity Study
      (CHARLS). CHARLS recruited a nationally representative community sample of
      households with members aged 45 years or above. A subsample of 742 respondents
      aged 60 years and older were used for this study. Confirmatory factor analyses
      were conducted to test three competing models and determine the best-fit model
      for the elderly Chinese sample. Factorial invariance across gender was also
      examined. R2 coefficient was used to measure the reliability of each item.
      RESULTS: Confirmatory factor analysis supported the two-factor model as having
      the best fit. Depressive affect and somatic symptoms were the first factor while
      positive affect was loaded as the second factor. The multi-group analysis showed
      that the two-factor structure varied across the male and female groups in China
      (chi2 (df = 86) = 144.13, p < 0.001). Moreover, gender differences were indicated
      by individual item reliability scores, mean score, and prevalence rate of
      depressive symptoms. CONCLUSION: The CES-D 10 Scale indicated adequate
      reliability and validity for the community-dwelling older population in China. In
      addition, the data revealed that perception and expression of depressive feelings
      was different between male and female elderly people.

PMID- 24125555
TI  - Imaging multiple sclerosis outside the brain.

PMID- 24125556
TI  - Differences between conventional and nonconventional MRI techniques in
      Parkinson's disease.
AB  - Magnetic resonance imaging (MRI) provides an in vivo assessment of cortical and
      subcortical regions affected in Parkinson's disease (PD). This review summarizes
      the most important conventional and non-conventional MRI techniques applied in
      this field. Standard neuroimaging techniques have played a marginal role in the
      diagnosis and follow-up of PD, essentially being used only to discriminate
      atypical syndromes from PD, to exclude secondary causes such as vascular lesions,
      and to confirm the absence of specific imaging features found in atypical
      parkinsonisms. However, non-conventional MRI techniques, i.e. new neuroimaging
      approaches such as magnetic resonance spectroscopy, diffusion tensor imaging, and
      functional MRI, may allow the detection of structural, functional and metabolic
      changes useful not only for differential diagnosis, but also for early diagnosis
      and outcome and treatment monitoring in PD. In addition, we illustrate the
      advantages of high-field MRI over lower magnetic fields, highlighting the great
      potential of advanced neuroimaging techniques.

PMID- 24125554
TI  - Mannosylation in Candida albicans: role in cell wall function and immune
      recognition.
AB  - The fungal cell wall is a dynamic organelle required for cell shape, protection
      against the environment and, in pathogenic species, recognition by the innate
      immune system. The outer layer of the cell wall is comprised of glycosylated
      mannoproteins with the majority of these post-translational modifications being
      the addition of O- and N-linked mannosides. These polysaccharides are exposed on
      the outer surface of the fungal cell wall and are, therefore, the first point of
      contact between the fungus and the host immune system. This review focuses on O-
      and N-linked mannan biosynthesis in the fungal pathogen Candida albicans and
      highlights new insights gained from the characterization of mannosylation mutants
      into the role of these cell wall components in host-fungus interactions. In
      addition, we discuss the use of fungal mannan as a diagnostic marker of fungal
      disease. 

PMID- 24125557
TI  - Dermatological and immunological conditions due to nerve lesions.
AB  - Some syndromes are of interest to both neurologists and dermatologists, because
      cutaneous involvement may harbinger symptoms of a neurological disease. The aim
      of this review is to clarify this aspect. The skin, because of its relationships
      with the peripheral sensory nervous system, autonomic nervous system and central
      nervous system, constitutes a neuroimmunoendocrine organ. The skin contains
      numerous neuropeptides released from sensory nerves. Neuropeptides play a precise
      role in cutaneous physiology and pathophysiology, and in certain skin diseases. A
      complex dysregulation of neuropeptides is a feature of some diseases of both
      dermatological and neurological interest (e.g. cutaneous and nerve lesions
      following herpes zoster infection, cutaneous manifestations of carpal tunnel
      syndrome, trigeminal trophic syndrome). Dermatologists need to know when a
      patient should be referred to a neurologist and should consider this option in
      those presenting with syndromes of unclear etiology.

PMID- 24125558
TI  - Development of a high-resolution fat and CSF-suppressed optic nerve DTI protocol
      at 3T: application in multiple sclerosis.
AB  - Clinical trials of neuroprotective interventions in multiple sclerosis require
      outcome measures that reflect the disease pathology. Measures of neuroaxonal
      integrity in the anterior visual pathways are of particular interest in this
      context, however imaging of the optic nerve is technically challenging. We
      therefore developed a 3T optic nerve diffusion tensor imaging protocol
      incorporating fat and cerebrospinal fluid suppression and without parallel
      imaging. The sequence used a scheme with six diffusion-weighted directions, b =
      600 smm(-2) plus one b ~ 0 (b(0)) and 40 repetitions, averaged offline, giving an
      overall scan time of 30 minutes. A coronal oblique orientation was used with
      voxel size 1.17 mm x 1.17 mm x 4 mm, We validated the sequence in 10 MS patients
      with a history of optic neuritis and 11 healthy controls: mean fractional
      anisotropy was reduced in the patients: 0.346(+/-0.159) versus 0.528(+/-0.123),
      p<0.001; radial diffusivity was increased: 0.940(+/-0.370)x10(-6) mm(2) s(-1)
      compared to 0.670(+/- 0.221)x10(-6) mm(2) s(-1) (p<0.01). No significant
      differences were seen for mean diffusivity or mean axial diffusivity.

PMID- 24125559
TI  - Tetrabenazine improves levodopa-induced peak-dose dyskinesias in patients with
      Parkinson's disease.
AB  - Since levodopa-induced peak dyskinesias (LIDs) may reflect, in part, a
      disproportionate phasic release of dopamine from synaptic vesicles, we examined
      the ability of the vesicular depletor tetrabenazine (TBZ) to reduce LIDs in 10
      dyskinetic advanced Parkinson's disease (PD) patients. After basal evaluation,
      the patients received, through a slow titration, oral TBZ twice a day for six
      weeks (up to 50 mg daily) before being re-assessed after a challenge with
      levodopa. The primary outcome measure was the change in the Unified Parkinson's
      Disease Rating Scale (UPDRS) dyskinesia score (items 32 to 34). TBZ was well
      tolerated. A clear treatment effect on LIDs emerged (up to 45%, p<0.05). In two
      patients a little worsening of motor performance necessitated an increase of the
      antiparkinsonian therapy, which did not worsen peak-dose LIDs. The patients
      experienced a clear benefit in terms of their quality of life. In this open-label
      pilot study, orally administered TBZ resulted in objective and subjective
      improvements in LIDs. Larger pharmacological studies are in progress.

PMID- 24125560
TI  - Non-genetic factors associated with the risk of Parkinson's disease in Iranian
      patients.
AB  - The aim of this study was to investigate some of nongenetic factors associated
      with Parkinson's disease (PD) in a sample of Iranian patients. This case-control
      study included 75 patients with idiopathic PD and 75 control patients. The
      patients in the control group were found to have drunk more glasses of tea per
      day than the case group before the onset of their problem (p=0.019). Every extra
      glass of tea per day decreased the risk of PD by 0.8 times (OR=0.8, 95%CI=0.73
      0.97, p=0.02). Each cup of coffee per week decreased the chance of developing PD
      by 0.5 times (OR=0.5, 95%CI=0.28-0.9, p=0.021). A previous history of evening
      work increased PD risk by 4.6 times (OR=4.6, 95%CI=1.29-16.86, p=0.019) while
      major stressful events increased it by 13.5 times (OR=13.5, 95%CI=4.7-38.1,
      p=0.0001). In conclusion, coffee and tea consumption may exert a protective
      effect against PD, while evening work and stress may be risk factors for the
      development of the disease.

PMID- 24125561
TI  - Depression, pain and quality of life in patients with amyotrophic lateral
      sclerosis: a cross-sectional study.
AB  - The complications related to amyotrophic lateral sclerosis (ALS) include pain. A
      higher risk of depression and a negative effect on quality of life (QoL) might be
      expected in ALS patients with pain. The aims of this study were to evaluate the
      prevalence of pain in ALS patients, to compare measures of depression and QoL in
      patients with and without pain, and to study the influence of depression scores
      and pain on the QoL of ALS patients with pain. Forty ALS patients were enrolled,
      and 36 were included in the analysis. Seventy-two percent of patients reported
      pain. Pain intensity was significantly related to a worsening of QoL (p<.05).
      This effect was no longer significant after considering depression scores as a
      covariate. Depression scores significantly decreased QoL (p<.02) and this effect
      remained significant after considering pain intensity as a covariate (p<.05). Our
      study suggests that pain is frequent in ALS patients and that depressive symptoms
      are significantly related to poorer QoL. Clinicians should pay more attention to
      both pain and depressive symptoms in ALS patients considering their effect on
      QoL.

PMID- 24125562
TI  - Psychometric properties of the Italian version of the Scales for Outcomes in
      Parkinson's disease- Cognition (SCOPA-Cog).
AB  - The Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) has been
      shown to be a clinimetrically rigorous and valid instrument for a disease
      oriented neuropsychological assessment of Parkinson's disease (PD) patients. In
      the present study we evaluated the psychometric properties of the Italian version
      of the SCOPA-Cog in 121 PD patients. The scale explores memory, attention, and
      executive and visuospatial functions and takes approximately 20 minutes to
      administer. Data distribution (skewness= -0.23) and internal consistency
      (Cronbach's alpha= 0.78) were satisfactory. Standard error of measurement was
      3.42. The outcome was significantly worse in patients with an abnormal
      Psychometric properties of the Italian version of the Scales for Outcomes in
      Parkinson's disease-Cognition (SCOPA-Cog) score on the Dementia Rating Scale
      (DRS) (SCOPACog mean score 14.6 +/- 5.1 out of a total of 43) with respect to
      cognitively intact subjects (24.2 +/- 4.3) (p<0.0001). The DRS showed good
      convergent validity (Spearman rho= 0.77, p<0.0001), and a high coefficient of
      variation (= 0.34). These findings support the goodness of the Italian SCOPA-Cog
      in terms of metrics and validity.

PMID- 24125564
TI  - Pure akinesia: a kinematic analysis in a case responsive to rotigotine.
AB  - A patient with pure akinesia is described. This rare gait disorder, poorly
      responsive to therapy, is characterized by gait impairment which may be
      associated with handwriting and speech difficulties, in the absence of further
      signs of extrapyramidal involvement. Here, we report the improvement in a patient
      suffering from pure akinesia after low doses of rotigotine, a non-ergolinic
      dopamine agonist, detailing the kinematic analysis before and after the
      treatment. After therapy, an improvement in all of the gait parameters,
      particularly gait speed, was observed with a trend toward normalization. Our case
      report suggests that rotigotine may be a therapeutic option in cases of pure
      akinesia.

PMID- 24125565
TI  - Gestational diabetes mellitus, programing and epigenetics.
AB  - Gestational diabetes mellitus (GDM) is a common medical complication in
      pregnancy. Offspring exposed to maternal hyperglycemia have a higher birth weight
      and are prone to develop metabolic disease in adult life. The intrauterine
      environmental or nutritional status seems to be involved in the fetal programing.
      The concept of "Developmental Origins of Health and Disease" (DOHaD) has been
      widely accepted and it brings new insights into the molecular pathogenesis of
      human diseases. The underlying mechanism is still under discussion and epigenetic
      mechanisms may provide an explanation for the phenomenon. The aim of this review
      is to illustrate the role of epigenetic modifications in the development of
      insulin resistance in metabolic diseases induced by adverse intrauterine
      exposures. Changes in epigenetic mechanism may be an early event in pathogenesis
      and progression of the metabolic disease in humans. Studies on epigenetic
      modifications contribute to our understanding of long-term effects of in utero
      exposure and shed light on the disease prevention and treatment by modulating
      epigenetic changes.

PMID- 24125563
TI  - A rare association of early-onset inclusion body myositis, rheumatoid arthritis
      and autoimmune thyroiditis: a case report and literature review.
AB  - Sporadic inclusion body myositis (sIBM) is a slowly progressive, red-rimmed
      vacuolar myopathy leading to muscular atrophy and progressive weakness; it
      predominantly affects males older than fifty years, and is resistant to
      immunotherapy. It has been described in association with immuno-mediated
      thrombocytopenic purpura, multiple sclerosis, connective tissue disorders and,
      occasionally, rheumatoid arthritis. A 37-year-old man with longstanding
      rheumatoid arthritis and autoimmune thyroiditis with hypothyroidism was referred
      to us with slowly progressive, diffuse muscle weakness and wasting, which had
      initially involved the volar finger flexors, and subsequently also the ankle
      dorsiflexors and knee extensors. Needle electromyography showed typical myopathic
      motor unit potentials, fibrillation and positive sharp waves with normal nerve
      conduction studies. Quadriceps muscle biopsy was suggestive of sIBM. Considering
      data published in the literature, this case may be classified as an early-onset
      form. The patient was treated with long-term intravenous immunoglobulin and
      obtained a substantial stabilization of his muscle strength.

PMID- 24125566
TI  - Dermoscopic features and follow-up changes of acral melanocytic naevi in
      childhood and adolescence.
AB  - BACKGROUND: The dermoscopic features of acral acquired melanocytic naevi have
      been extensively reported in the adult population. Little knowledge is available
      on acral naevi in childhood and adolescence. OBJECTIVES: Firstly, to characterize
      the frequency of dermoscopic features of acral naevi and their distribution
      according to age groups in children and adolescents; and secondly, to analyse the
      type and frequency of their dermoscopic changes over time. METHODS: A
      retrospective evaluation of baseline and follow-up dermoscopic images of acral
      naevi in Italian patients aged 0-18 years was carried out. RESULTS: Dermoscopic
      images of 75 acral naevi (39 in children and 36 in adolescents) in 69 patients
      were evaluated. The parallel furrow was the most common pattern (71%), followed
      by the crista dotted pattern (21%). A difference in the distribution of global
      patterns was observed between children and adolescents (P = 0.02). Combination
      patterns were detected in 32% of lesions, with association of the crista dotted
      and parallel furrow patterns in 62% of these. Follow-up images were available for
      31/75 acral naevi (41%), with a median follow-up period of 32 months (range 4
      85). Morphological variations during follow-up were identified in 61% of lesions.
      Global changes involved mainly naevi with a baseline parallel furrow pattern,
      after a follow-up of > 30 months. A decrease of local criteria during follow-up
      was observed in 48% of lesions. CONCLUSIONS: Parallel furrow and crista dotted
      patterns, either alone or in combination, were the most common dermoscopic
      patterns. Morphological changes during follow-up were frequent, involving mainly
      the parallel furrow pattern with a decrease of local criteria. Recognition of the
      dermoscopic features of acral naevi of children and adolescents is important to
      improve proper management and reduce the number of unnecessary excisions.

PMID- 24125567
TI  - The influence of disease duration, clinical course, and immunosuppressive therapy
      on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis.
AB  - We investigated the impact of disease duration, clinical course and
      immunosuppressive therapy on intrathecal IgG synthesis in multiple sclerosis
      (MS). Cerebrospinal fluid (CSF) was obtained twice, 8-10 years apart, from 20 MS
      patients and 26 healthy controls, and from 22 MS patients before and after two
      years of mitoxantrone treatment. The oligoclonal IgG band patterns changed in 15
      patients at long-term follow-up, but were only influenced in 4 patients by
      mitoxantrone therapy. The CSF B-cell-regulating chemokine CXCL13 correlated with
      intrathecal IgG production suggesting a B-cell-dependence of intrathecal IgG
      synthesis in MS.

PMID- 24125568
TI  - A focus on mast cells and pain.
AB  - Mast cells (MCs) are immunocytes with secretory functions that act locally in
      peripheral tissues to modulate local hemodynamics, nociceptor activation and
      pain. They are also able to infiltrate the central nervous system (CNS),
      especially the spinal cord and the thalamus, but their cerebral function remains
      an enigma. A role in regulating the opening of the blood-brain barrier has been
      proposed. Paracrine-like action of MCs on synaptic transmission might also signal
      a modulation of the nervous system by the immune system. In this review, we
      examine the link between MCs and nociceptive process, at the periphery as well as
      in the CNS. 

PMID- 24125569
TI  - Polysaccharides from medicinal herbs as potential therapeutics for aging and age
      related neurodegeneration.
AB  - Recent studies have uncovered important aging clues, including free radicals,
      inflammation, telomeres, and life span pathways. Strategies to regulate aging
      associated signaling pathways are expected to be effective in the delay and
      prevention of age-related disorders. For example, herbal polysaccharides with
      considerable anti-oxidant and anti-inflammation capacities have been shown to be
      beneficial in aging and age-related neurodegenerative diseases. Polysaccharides
      capable of reducing cellular senescence and modulating life span via telomere and
      insulin pathways have also been found to have the potential to inhibit protein
      aggregation and aggregation-associated neurodegeneration. Here we present the
      current status of polysaccharides in anti-aging and anti-neurodegenerative
      studies.

PMID- 24125570
TI  - New insights into pediatric idiopathic pulmonary hemosiderosis: the French
      RespiRare((r)) cohort.
AB  - BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar
      hemorrhage in children and its pathophysiology remains obscure. Classically,
      diagnosis is based on a triad including hemoptysis, diffuse parenchymal
      infiltrates on chest X-rays, and iron-deficiency anemia. We present the French
      pediatric cohort of IPH collected through the French Reference Center for Rare
      Lung Diseases (RespiRare(r), http://www.respirare.fr). METHODS: Since 2008, a
      national network/web-linked RespiRare(r) database has been set up in 12 French
      pediatric respiratory centres. It is structured as a medical recording tool with
      extended disease-specific datasets containing clinical information relevant to
      all forms of rare lung diseases including IPH. RESULTS: We identified 25 reported
      cases of IPH in children from the database (20 females and 5 males). Among them,
      5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0]
      yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16,
      64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n =
      11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on
      chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage
      indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung
      biopsy (6/25). In screened patients, initial auto-immune screening revealed
      positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear
      antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4,
      28%). All the patients were initially treated by corticosteroids. In 13 cases,
      immunosuppressants were introduced due to corticoresistance and/or major side
      effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory
      outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and
      another with Down syndrome died as a result of severe pulmonary hemorrhage.
      CONCLUSION: The present cohort provides substantial information on clinical
      expression and outcomes of pediatric IPH. Analysis of potential contributors
      supports a role of auto-immunity in disease development and highlights the
      importance of genetic factors.

PMID- 24125571
TI  - [Acute polyradiculoneuropathy revealing systemic lupus erythematosus: an unusual
      presentation with fatal outcome].
AB  - INTRODUCTION: Neurological manifestations of systemic lupus erythematosus are
      common and numerous. They mainly involve the central nervous system, peripheral
      involvement being rare. Acute polyradiculoneuropathy is very uncommon. CASE
      REPORT: We report a 44-year-old man, who presented with acute
      polyradiculoneuropathy revealing systemic lupus erythematosus. Outcome was fatal
      despite treatment with corticosteroids and immunoglobulin. CONCLUSION: Acute
      polyradiculoneuropathy is a very rare manifestation of systemic lupus
      erythematosus and can compromise functional and life prognosis. Early diagnosis
      and management are crucial.

PMID- 24125572
TI  - Aziridine nitrogen inversion by dynamic NMR: activation parameters in a fused
      bicyclic structure.
AB  - The nitrogen inversion of a N-phenyl aziridine fused to a succinimide ring is
      influenced by the presence of a phenyl ring in the succinimide moiety. The endo
      invertomer is favored, showing an unsymmetrical equilibrium in variable (1)H NMR
      studies. 

PMID- 24125573
TI  - Current themes in the neurobiology of language: Highlights from the third annual
      Neurobiology of Language Conference (NLC 2011).

PMID- 24125575
TI  - Glycosaminoglycan degradation by selected reactive oxygen species.
AB  - SIGNIFICANCE: Inflammatory diseases (such as arthritis) of the extracellular
      matrix (ECM) are of considerable socioeconomic significance. There is clear
      evidence that reactive oxygen species (ROS) and nitrogen species released by, for
      instance, neutrophils contribute to the degradation of the ECM. Here we will
      focus on the ROS-induced degradation of the glycosaminoglycans, one important
      component of the ECM. RECENT ADVANCES: The recently developed "anti-TNF-alpha"
      therapy is primarily directed against neutrophilic granulocytes that are powerful
      sources of ROS. Therefore, a more detailed look into the mechanisms of the
      reactions of these ROS is reasonable. CRITICAL ISSUES: Since both enzymes and ROS
      contribute to the pathogenesis of inflammatory diseases, it is very difficult to
      estimate the contributions of the individual species in a complex biological
      environment. This particularly applies as many products are not stable but only
      transient products that decompose in a time-dependent manner. Thus, the
      development of suitable analytical methods as well as the establishment of useful
      biomarkers is a challenging aspect. FUTURE DIRECTIONS: If the mechanisms of ECM
      destruction are understood in more detail, then the development of suitable drugs
      to treat inflammatory diseases will be hopefully much more successful.

PMID- 24125574
TI  - Do temporal processes underlie left hemisphere dominance in speech perception?
AB  - It is not unusual to find it stated as a fact that the left hemisphere is
      specialized for the processing of rapid, or temporal aspects of sound, and that
      the dominance of the left hemisphere in the perception of speech can be a
      consequence of this specialization. In this review we explore the history of this
      claim and assess the weight of this assumption. We will demonstrate that instead
      of a supposed sensitivity of the left temporal lobe for the acoustic properties
      of speech, it is the right temporal lobe which shows a marked preference for
      certain properties of sounds, for example longer durations, or variations in
      pitch. We finish by outlining some alternative factors that contribute to the
      left lateralization of speech perception. 

PMID- 24125576
TI  - Potential bias in research of heart rate variability in fibromyalgia and chronic
      fatigue syndrome.

PMID- 24125577
TI  - Antibody-free LC-MS/MS quantification of rhTRAIL in human and mouse serum.
AB  - The major challenge in targeted protein quantification by LC-MS/MS in serum lies
      in the complexity of the biological matrix with regard to the wide diversity of
      proteins and their extremely large dynamic concentration range. In this study, an
      LC-MS/MS method was developed for the simultaneous quantification of the 60-kDa
      biopharmaceutical proteins recombinant human tumor necrosis factor-related
      apoptosis-inducing ligand wild type (rhTRAIL(WT)) and its death receptor 4 (DR4)
      specific variant rhTRAIL(4C7) in human and mouse serum. Selective enrichment of
      TRAIL was accomplished by immobilized metal affinity chromatography (IMAC), which
      was followed by tryptic digestion of the enriched sample and quantification of a
      suitable signature peptide. For absolute quantification, (15)N-metabolically
      labeled internal standards of rhTRAIL(WT) and rhTRAIL(4C7) were used. Since the
      signature peptides that provided the highest sensitivity and allowed
      discrimination between rhTRAIL(WT) and rhTRAIL(4C7) contained methionine
      residues, we oxidized these quantitatively to their sulfoxides by the addition of
      0.25% (w/w) hydrogen peroxide. The final method has a lower limit of
      quantification of 20 ng/mL (ca. 350 pM) and was fully validated according to
      current international guidelines for bioanalysis. To show the applicability of
      the LC-MS/MS method for pharmacokinetic studies, we quantified rhTRAIL(WT) and
      rhTRAIL(4C7) simultaneously in serum from mice injected intraperitoneally at a
      dose of 5 mg/kg for each protein. This is the first time that two variants of
      rhTRAIL differing by only a few amino acids have been analyzed simultaneously in
      serum, an approach that is not possible by conventional enzyme-linked immuno
      sorbent assay (ELISA) analysis. 

PMID- 24125578
TI  - Should chitosan and tranexamic acid be combined for improved hemostasis after
      sinus surgery?
AB  - Chitosan, a beta-1,4-linked polymer of glucosamine with lesser amounts of N
      acetylglucosamine, has well-recognized hemostatic properties. Chitosan is also
      able to open tight cellular junctions, facilitating paracellular drug transport
      and delivery. Chitosan, through topical application, facilitates the systemic
      delivery of analgesic drugs. Theoretically this ability could be used to enhance
      the local delivery of hemostatic drugs, such as tranexamic acid, improving
      chitosan's role as a topical dressing. Individually a chitosan-dextran gel and
      tranexamic acid have been shown to improve hemostasis after endoscopic sinus
      surgery. A combination of both should lead to improved hemostasis and better
      postsurgical outcomes. The use of a chitosan/tranexamic acid dressing could have
      a wide range of potential beneficial applications in a number of other clinical
      surgical settings. While the initial main application might be as an improved
      external hemostatic dressing, it should also be useful on a range of internal
      surgical wounds. 

PMID- 24125579
TI  - Eosinophilic fasciitis: an uncommon cause of edema.

PMID- 24125580
TI  - Correlations between carotid plaque progression and mechanical stresses change
      sign over time: a patient follow up study using MRI and 3D FSI models.
AB  - BACKGROUND: Increasing evidence suggests that mechanisms governing advanced
      plaque progression may be different from those for early progression and require
      further investigation. Serial MRI data and 3D fluid-structure interaction (FSI)
      models were employed to identify possible correlations between mechanical
      stresses and advanced plaque progression measured by vessel wall thickness
      increase (WTI). Long-term patient follow up was used to gather data and
      investigate if the correlations identified above were reproducible. METHODS: In
      vivo MRI data were acquired from 16 patients in a follow-up study with 2 to 4
      scans for each patient (scan interval: average 18 months and standard deviation
      6.8 months). A total of 38 scan pairs (baseline and follow-up) were formed for
      analysis using the carotid bifurcation as the registration point. 3D FSI models
      were constructed to obtain plaque wall stress (PWS) and flow shear stress (FSS)
      to quantify their correlations with plaque progression. The Linear Mixed-Effects
      models were used to study possible correlations between WTI and baseline PWS and
      FSS with nodal dependence taken into consideration. RESULTS: Of the 38 scan
      pairs, 22 pairs showed positive correlation between baseline PWS and WTI, 1 pair
      showed negative correlation, and 15 pairs showed no correlation. Thirteen
      patients changed their correlation sign (81.25%). Between baseline FSS and WTI,
      16 pairs showed negative correlation, 1 pair showed positive correlation. Twelve
      patients changed correlation sign (75%). CONCLUSION: Our results showed that
      advanced plaque progression had an overall positive correlation with plaque wall
      stress and a negative correlation with flow shear stress at baseline. However,
      long-term follow up showed that correlations between plaque progress and
      mechanical stresses (FSS and PWS) identified for one time period were not re
      producible for most cases (>80%). Further investigations are needed to identify
      the reasons causing the correlation sign changes.

PMID- 24125581
TI  - Urolithins display both antioxidant and pro-oxidant activities depending on assay
      system and conditions.
AB  - The biological effects of polyphenolic ellagitannins are mediated by their
      intestinal metabolites, urolithins. This study investigated redox properties of
      urolithins A and B using ORAC assay, three cell-based assays, copper-initiated
      pro-oxidant activity (CIPA) assay, and cyclic voltammetry. Urolithins were strong
      antioxidants in the ORAC assay, but mostly pro-oxidants in cell-based assays,
      although urolithin A was an antioxidant in cell culture medium. Parent compound
      ellagic acid was a strong extracellular antioxidant, but showed no response in
      the intracellular assay. The CIPA assay confirmed the pro-oxidant activity of
      ellagitannin metabolites. In the cell proliferation assay, urolithins but not
      ellagic acid decreased growth and metabolism of HepG2 liver cells. In cyclic
      voltammetry, the oxidation of urolithin A was partly reversible, but that of
      urolithin B was irreversible. These results illustrate how strongly measured
      redox properties depend on the employed assay system and conditions and emphasize
      the importance of studying pro-oxidant and antioxidant activities in parallel. 

PMID- 24125582
TI  - Early repair of congenital heart disease associated with increased rate of
      attention deficit hyperactivity disorder symptoms.
AB  - BACKGROUND: As more children survive with congenital heart disease, their
      neurodevelopmental outcomes (including attention deficit hyperactivity disorder
      [ADHD]) are becoming increasingly important. The objective of our study was to
      determine if school-aged children who underwent early cardiac surgery for
      congenital heart disease are more likely than healthy control subjects to have
      screening scores on the Swanson, Nolan, and Pelham IV (SNAP-IV) questionnaire
      suggestive of ADHD. METHODS: Children aged 7-15 years who underwent open-heart
      surgery before 1 year of age were identified from the Izaak Walton Killam (IWK)
      Children's Heart Centre Database. Control subjects were recruited from healthy
      volunteers. The SNAP-IV questionnaire was administered to all participants and a
      chart review was performed on all eligible children in the cardiac surgery group.
      Case and control subjects were compared using Fisher's exact test, linear, and
      logistic regression analyses. Potential predictors of a positive screening score
      were sought. RESULTS: A positive screening score was found in 29% (16/56) of the
      surgical group compared with 3% (2/60) of the control group (P < 0.001). Surgical
      and control subjects differed in average overall scores (0.93 vs 0.30; P < 0.001)
      and in scores for hyperactivity (0.83 vs 0.24; P < 0.001) and inattention (1.04
      vs 0.37; P < 0.001). No other significant predictors of a positive screening
      score were identified. The early open-heart surgery participants who responded to
      the questionnaire did not differ in baseline characteristics compared with
      nonresponders. CONCLUSIONS: Children who have open-heart surgery at younger than
      1 year of age are more likely than healthy control subjects to have a SNAP-IV
      score suggestive of ADHD when they reach school age.

PMID- 24125584
TI  - On measurements and their quality. Paper 4: verbal anchors and the number of
      response options in rating scales.
AB  - This is the last in a short series of papers on measurement theory and practice
      with particular relevance to intervention research in nursing, midwifery, and
      healthcare. Understanding how it is that people respond to the questions posed by
      researchers is fundamental to progress in the social and health sciences. For
      decades methodologists in psychology, marketing, education, and survey research
      have studied this issue. In this paper I review this diverse empirical literature
      to synthesize basic principles for creating rating scales which can reduce
      measurement error and increase the quality of resulting data. After introducing a
      theoretical framework known as the cognitive aspects of survey methods (CASM), I
      review the fundamentals of psychological scaling theory and discuss how it has
      been used to study the meanings of verbal response options and provide an
      illustration of how the quality of measurements may be influenced by our choice
      of the verbal phrases we present as response options. Next, I review the research
      on the optimal number of response options to use in various measurement
      situations and how verbal and numeric anchors can combine to influence data
      quality. Finally, I summarize the issues covered and present recommendations for
      best practice when creating and using rating scales in research. 

PMID- 24125583
TI  - Nanoscale ligand spacing influences receptor triggering in T cells and NK cells.
AB  - Bioactive nanoscale arrays were constructed to ligate activating cell surface
      receptors on T cells (the CD3 component of the TCR complex) and natural killer
      (NK) cells (CD16). These arrays are formed from biofunctionalized gold
      nanospheres with controlled interparticle spacing in the range 25-104 nm.
      Responses to these nanoarrays were assessed using the extent of membrane
      localized phosphotyrosine in T cells stimulated with CD3-binding nanoarrays and
      the size of cell contact area for NK cells stimulated with CD16-binding
      nanoarrays. In both cases, the strength of response decreased with increasing
      spacing, falling to background levels by 69 nm in the T cell/anti-CD3 system and
      104 nm for the NK cell/anti-CD16 system. These results demonstrate that immune
      receptor triggering can be influenced by the nanoscale spatial organization of
      receptor/ligand interactions. 

PMID- 24125585
TI  - The nursing practice environment.

PMID- 24125586
TI  - Overview of beverages with anti-aging functions in Chinese market.
AB  - Anti-aging Chinese medicines have been used in traditional beverages to promote
      health and prevent diseases. Interestingly, these functional beverages may be
      used differently between men and women, reflecting the "yin-yang" philosophy of
      Chinese medicine. Modern studies have revealed that some dietary natural products
      can slow aging in model organisms, and functional beverages containing such
      products have recently emerged in Chinese market, challenging the dominance of
      traditional functional beverages. Here we summarize both traditional anti-aging
      herbs and modern natural dietary compounds currently used in functional beverages
      in China, and also briefly outline the underlying mechanisms of the beverages in
      slowing aging process.

PMID- 24125588
TI  - Small-diameter vascular graft engineered using human embryonic stem cell-derived
      mesenchymal cells.
AB  - Despite the progress made thus far in the generation of small-diameter vascular
      grafts, cell sourcing still remains a problem. Human embryonic stem cells (hESCs)
      present an exciting new cell source for the regeneration applications due to
      their high proliferative and differentiation capabilities. In this study, the
      feasibility of creating small-diameter vascular constructs using smooth muscle
      cells (SMCs) differentiated from hESC-derived mesenchymal cells was evaluated. In
      vitro experiments confirmed the ability of these cells to differentiate into
      smooth muscle actin- and calponin-expressing SMCs in the presence of known
      inducers, such as transforming growth factor beta. Human vessel walls were
      constructed by culturing these cells in a bioreactor system under pulsatile
      conditions for 8 weeks. Histological analysis showed that vessel grafts had
      similarities to their native counterparts in terms of cellularity and SMC marker
      expression. However, markers of cartilage and bone tissue were also detected,
      thus raising questions about stable lineage commitment during differentiation and
      calling for more stringent analysis of differentiating cell populations. 

PMID- 24125587
TI  - A tale of two machines: a review of the BLAST meeting, Tucson, AZ, 20-24 January
      2013.
AB  - Since its inception, Bacterial Locomotion and Signal Transduction (BLAST)
      meetings have been the place to exchange and share the latest developments in the
      field of bacterial signal transduction and motility. At the 12th BLAST meeting,
      held last January in Tucson, AZ, researchers from all over the world met to
      report and discuss progress in diverse aspects of the field. The majority of
      these advances, however, came at the level of atomic level structures and their
      associated mechanisms. This was especially true of the biological machines that
      sense and respond to environmental changes.

PMID- 24125589
TI  - Construction and application of a novel hepatocyte-directed vector to
      simultaneous knockdown and overexpression of multiple genes.
AB  - BACKGROUND & AIMS: Liver disease, such as malignancy and hepatitis, often
      correlates with several genetic disorders. We aimed to construct a hepatocyte
      specific vector that could manipulate multiple genes simultaneously. METHODS: We
      selected a highly efficient hepatocyte-specific alpha-foetoprotein (AFP)
      enhancer/albumin promoter (an RNA polymerase II promoter) to express our gene of
      interest and transcribe microRNA-based shRNAs (shRNAmir). Multiple shRNAmirs were
      assembled together in tandem to enhance the gene-silencing effect. By employing
      the AFP enhancer/albumin promoter and inserting an internal ribosome entry site
      (IRES), a hepatocyte-specific, multi-reporter vector that overexpressed both beta
      galactosidase (LacZ) and DsRed2 while simultaneously knocking down both EGFP and
      luciferase expression was successfully constructed and functionally tested in
      vitro. RESULTS: The reporter genes in the multireporter vector were easily
      replaced by immune-related genes to construct the Multi-Vector, which
      overexpressed human interleukin 10 and silenced both CCL5 and CX3CL1 (FKN)
      simultaneously in vivo; visualization of DsRed2 coexpressed to monitor vector
      function in vivo confirmed that the Multi-Vector was successfully introduced into
      the host. Simultaneous manipulation of these multiple genes by the Multi-Vector
      synergistically inhibited acute liver injury induced by Poly I:C/D-GalN injection
      in mice. The multifunctional cassette was also packaged in and successfully
      delivered by an adenoviral vector. CONCLUSIONS: We successfully engineered a
      vector that can simultaneously regulate multiple genes from a single multigene
      containing vector in a hepatocyte-specific manner, suggesting the possibility
      that this method could be extensively and practically utilized in liver gene
      therapy.

PMID- 24125590
TI  - Reducing multi-sensor data to a single time course that reveals experimental
      effects.
AB  - BACKGROUND: Multi-sensor technologies such as EEG, MEG, and ECoG result in high
      dimensional data sets. Given the high temporal resolution of such techniques,
      scientific questions very often focus on the time-course of an experimental
      effect. In many studies, researchers focus on a single sensor or the average over
      a subset of sensors covering a "region of interest" (ROI). However, single-sensor
      or ROI analyses ignore the fact that the spatial focus of activity is constantly
      changing, and fail to make full use of the information distributed over the
      sensor array. METHODS: We describe a technique that exploits the optimality and
      simplicity of matched spatial filters in order to reduce experimental effects in
      multivariate time series data to a single time course. Each (multi-sensor) time
      sample of each trial is replaced with its projection onto a spatial filter that
      is matched to an observed experimental effect, estimated from the remaining
      trials (Effect-Matched Spatial filtering, or EMS filtering). The resulting set of
      time courses (one per trial) can be used to reveal the temporal evolution of an
      experimental effect, which distinguishes this approach from techniques that
      reveal the temporal evolution of an anatomical source or region of interest.
      RESULTS: We illustrate the technique with data from a dual-task experiment and
      use it to track the temporal evolution of brain activity during the psychological
      refractory period. We demonstrate its effectiveness in separating the means of
      two experimental conditions, and in significantly improving the signal-to-noise
      ratio at the single-trial level. It is fast to compute and results in readily
      interpretable time courses and topographies. The technique can be applied to any
      data-analysis question that can be posed independently at each sensor, and we
      provide one example, using linear regression, that highlights the versatility of
      the technique. CONCLUSION: The approach described here combines established
      techniques in a way that strikes a balance between power, simplicity, speed of
      processing, and interpretability. We have used it to provide a direct view of
      parallel and serial processes in the human brain that previously could only be
      measured indirectly. An implementation of the technique in MatLab is freely
      available via the internet.

PMID- 24125592
TI  - Targeted reduction in neurosurgical laboratory utilization: resident-led effort
      at a single academic institution.
AB  - OBJECT: Given economic limitations and burgeoning health care costs, there is a
      need to minimize unnecessary diagnostic laboratory tests. METHODS: The authors
      studied whether a financial incentive program for trainees could lead to fewer
      unnecessary laboratory tests in neurosurgical patients in a large, 600-bed
      academic hospital setting. The authors identified 5 laboratory tests that ranked
      in the top 13 of the most frequently ordered during the 2010-2011 fiscal year,
      yet were least likely to be abnormal or influence patient management. RESULTS: In
      a single year of study, there was a 47% reduction in testing of serum total
      calcium, ionized calcium, chloride, magnesium, and phosphorus. This reduction led
      to a savings of $1.7 million in billable charges to health care payers and
      $75,000 of direct costs to the medical center. In addition, there were no
      significant negative changes in the quality of care delivered, as recorded in a
      number of metrics, showing that this cost savings did not negatively impact
      patient care. CONCLUSIONS: Engaging physician trainees in quality improvement can
      be successfully achieved by financial incentives. Through the resident-led
      quality improvement incentive program, neurosurgical trainees successfully
      reduced unnecessary laboratory tests, resulting in significant cost savings to
      both the medical center and the health care system. Similar programs that engage
      trainees could improve the value of care being provided at other academic medical
      centers.

PMID- 24125593
TI  - Expanding tandem mass spectral libraries of phosphorylated peptides: advances and
      applications.
AB  - The identification of phosphorylated proteins remains a challenge in proteomics,
      partially due to the difficulty in assigning tandem mass (MS/MS) spectra to their
      originating peptide sequences with correct phosphosite localization. Because of
      its advantages in efficiency and sensitivity, spectral library searching is a
      promising alternative to conventional sequence database searching. Our work aims
      to construct the largest collision-induced dissociation (CID) MS/MS spectral
      libraries of phosphorylated peptides in human (Homo sapiens) and four model
      organisms (Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis
      elegans, and Mus musculus) to date, to facilitate phosphorylated peptide
      identification by spectral library searching. We employed state-of-the-art search
      methods to published data and applied two recently published phosphorylation site
      localization tools (PhosphoRS and PTMProphet) to ascertain the phosphorylation
      sites. To further increase the coverage of this library, we predicted "semi
      empirical" spectra for peptides containing known phosphorylation sites from the
      corresponding template unphosphorylated peptide spectra. The performance of the
      spectral libraries built were evaluated and found to be superior to conventional
      database searching in terms of sensitivity. Updated spectral libraries of
      phosphorylated peptides are made freely available for use with the spectral
      search engine SpectraST. The work flow being developed will be used to
      continuously update the libraries when new data become available. 

PMID- 24125594
TI  - [Low diagnostic yield of the 11C-choline PET/CT in the detection of liver
      metastasis from prostate cancer].

PMID- 24125596
TI  - Theoretical studies of ring-opening reactions of phenylcyclobutabenzenol and its
      reactions with alkynes catalyzed by rhodium complexes.
AB  - DFT calculations have been carried out to study the Rh-catalyzed site selective
      ring-opening reactions of phenylcyclobutabenzenol (1a). Our calculations
      supported that the mechanism involves beta-carbon elimination in a rhodium(I)
      phenylcyclobutabenzenolato complex followed by alcoholysis. The favorable beta
      carbon elimination involves the cleavage of the C(sp(2))-C(sp(3))(OH)(Ph) bond in
      1a, which determines the site selectivity. The mechanism and regioselectivity of
      the related Rh-catalyzed insertion reaction of the asymmetric alkyne MeC=CPh with
      phenylcyclobutabenzenol (1a) was also investigated. The key step involves the
      alkyne insertion into the Rh-C sigma bond of a species resulting from the
      favorable beta-carbon elimination in the rhodium(I) phenylcyclobutabenzenolato
      complex. The favorable insertion couples the metal-bonded carbon with the methyl
      substituted carbon of MeC=CPh. 

PMID- 24125595
TI  - Comparison of 99mTc-sestamibi and 11C-methionine PET/CT in the localization of
      parathyroid adenomas in primary hyperparathyroidism.
AB  - AIM: To evaluate the usefulness of (11)C-methionine PET/CT (MET) in the
      localization of the parathyroid adenomas and to compare the results with those
      obtained with the conventional technique in double-phase (99m)Tc-sestamibi
      scintigraphy (MIBI). We evaluated the optimal timing to acquire MET images.
      MATERIAL AND METHODS: A prospective study that included 14 patients (mean age:
      65.5 +/- 9.7 years) with primary hyperparathyroidism (PH) who underwent surgery
      was performed. Mean serum iPTH was 215.8 +/- 108 pg/mL and serum calcium 10.8 +/-
      0.9 mg/dL. MIBI (planar and SPECT) was obtained 10 min and 2-3h after injection
      of 740 MBq (20 mCi) of (99m)Tc-sestamibi. MET was obtained 10 min and 40 min
      after injection of 740 MBq (20 mCi) of (11)C-methionine. MIBI and MET images were
      visually evaluated and compared. A score for 10 min and 40 min MET images from 0
      (no abnormal uptake) to 3 (intense uptake) was assigned. RESULTS: MIBI and MET
      were positive and concordant in 11/14 patients and in 10 of them the parathyroid
      adenoma was correctly localized. In 3/14 MIBI was positive and MET negative (MIBI
      correctly localized the parathyroid adenoma in 2 of them). According to the
      timing of MET imaging acquisition, the 10 min and 40 min acquisition showed the
      same score in 10 patients, it was higher at 10 min acquisition in 3 and in 1 the
      parathyroid adenoma was only detected at 40 min acquisition. CONCLUSION: MIBI
      remains the technique of choice for the localization of parathyroid adenomas in
      patients with PH. MET may play a complementary role in selected patients. Delayed
      acquisition should be included in the MET protocol when the early acquisition is
      negative.

PMID- 24125597
TI  - Thalassemia and the hypercoagulable state.
AB  - Thalassemia, an inherited hemolytic disorder, is associated with a high incidence
      of thrombosis. The major mechanisms underlying thromboembolism (TE) are an
      abnormal red blood cell surface, platelet activation and endothelial cell
      activation. A higher risk of TE is found in splenectomized patients due to
      thrombocytosis and increased abnormal RBCs in the circulation. Regular RBC
      transfusions can reduce the proportion of abnormal RBCs and suppress
      erythropoiesis. Regular transfusion may also reduce levels of circulating
      coagulation markers and reduce elevated pulmonary artery pressure. To prevent
      thromboembolic events, aspirin is now recommended for splenectomized patients
      with thrombocytosis. 

PMID- 24125599
TI  - [HCV prevalence among the populations under the HIV sentinel surveillance data
      from 2009 to 2012 in China].
AB  - OBJECTIVE: To analyze the hepatitis C virus (HCV) prevalence among 8 populations
      in 2009-2012 in China, using the HIV sentinels surveillance data. METHODS: Cross
      sectional studies had been repeatedly conducted on HIV Sentinel Surveillance with
      uniformed questionnaire and collection of venous blood specimen among 8
      populations including drug users (DUs), men who have sex with men(MSM), female
      sex workers(FSW), male STD clinic attendees, male long distance truck drivers,
      male mobile populations, pregnant women and young students from April to June
      2009 to 2012 on the yearly base. Blood testing for HIV, syphilis and HCV
      infections have been routinely performed on all participants of 8 populations
      recruited during the surveillance period. RESULTS: HCV prevalence among drug
      users had been relatively high, between 40.0%-43.0% in 2009-2012. HCV prevalence
      of injection drug users(IDUs)showing a slight increasing trend in the past four
      years from 55.0% in 2009 to 65.0% in 2012. HCV prevalence rates among other 7
      populations maintained low remained less than 1.0% in the past three years.
      CONCLUSION: Data from sentinel surveillance programs showed that HCV prevalence
      of DUs maintained high but the other 7 populations at low levels in the HIV
      sentinel surveillance areas in China. Blood-borne was the most common
      transmission pathways of HCV. IDU was one of the predominant models of HCV
      transmission in China and continued to fuel the HCV epidemics throughout the
      country.

PMID- 24125598
TI  - Snake bites and hemostasis/thrombosis.
AB  - Snake venom toxins have evolved to affect many prey physiological systems
      including hemostasis and thrombosis. These toxins belong to a diverse array of
      protein families and can initiate or inhibit multiple stages of the coagulation
      pathway or platelet aggregation with incredible specificity. Such specificity
      toward vertebrate molecular targets has made them extremely useful for diagnosis
      of human diseases or as molecular scalpels in physiological studies. The large
      number of yet-to-be characterized venoms provides a vast potential source of
      novel toxins and subsequent cardiovascular therapeutics and diagnostic agents. 

PMID- 24125600
TI  - [Epidemiological characteristics of hepatitis C in China, 1997-2011].
AB  - OBJECTIVE: To analyze the epidemiological characteristics and changing trend as
      well as the related affecting factors of hepatitis C in China. METHODS: Data
      analysis was performed based on the case-reporting data of hepatitis C from 1997
      to 2011, using SPSS 19.0. RESULTS: The number of reported cases and incidence of
      hepatitis C had been increasing annually since 1997, especially in 2004. The
      hepatitis C reported incidence increased from 3.03 per 100 000 in 2004, to 12.97
      per 100 000 in 2011. The 15 to 49 age group accounted for more than 50% of all
      the reported cases, seen in every year. The number and proportion of hepatitis C
      reported cases among those over 50 year-olds had an annually increase. From 2005
      to 2011, the number of cases in both urban areas and rural areas increased
      annually, while the urban-rural ratio decreased from 1.47 in 2005 to 0.99 in
      2011. There appeared an increasing trend of hepatitis C reported incidence in
      China, with most of the high reported incidence of hepatitis C fell in the
      northern parts of China. 74.8% of the HCV/HIV co-infected cases had histories of
      intravenous drug use, plasma donation, blood transfusion or surgical operation.
      CONCLUSION: The reported number and incidence of HCV infection had been
      increasing annually. To develop a more realistic control measures for hepatitis
      C, it is necessary to strengthen the monitoring program and carrying out specific
      epidemiological study among target groups and key areas.

PMID- 24125601
TI  - [Study on the incidence and risk factors of HCV infection among heroin addicts
      who were on methadone maintenance treatment in Dehong prefecture,Yunnan
      province].
AB  - OBJECTIVE: To determine the incidence and risk factors of HCV infection among
      heroin addicts who were receiving methadone maintenance treatment(MMT)in Dehong
      prefecture, Yunnan province. METHODS: All heroin addicts who were HCV negative at
      the initiation of MMT in June 2005 through March 2012, in Dehong prefecture, were
      included in this cohort analysis. HCV incidence was calculated and related risk
      factors determined by using Cox proportional hazard regression model. RESULTS: A
      total of 2390 MMT clinic attendants were qualified for this cohort study by March
      2012. 731(30.6%) of them had never received any follow-up HCV testing so were
      recognized as loss to follow-up. The other 1659 (69.4%) participants had received
      at least one follow-up HCV testing and were observed for a total of 3509.12
      person-years(py). During this period 99 new HCV infections or HCV sero-converters
      were identified. The overall HCV incidence was 2.82/100 py and was 3.62/100 py
      for 2006, 5.36/100 py for 2007, 6.71/100 py for 2008, 2.56/100 py for 2009,
      1.90/100 py for 2010, and 0.44/100 py for 2011, respectively. Results from
      multiple regression analysis, using Cox proportional hazard model, indicated that
      after controlling for confounding variables, those who were unemployed, being
      injecting drug users(IDUs)or HIV positive at entry into the MMT program were more
      likely to be newly infected with HCV or HCV sero-converted during the follow-up
      period than those who were peasants, non-IDUs or HIV negative at entry into the
      MMT program(HR = 2.02, 95% CI:1.18-3.48; HR = 9.05, 95% CI:5.49-14.93; HR = 2.12,
      95% CI: 1.37-3.56), respectively. CONCLUSION: The incidence of HCV infection
      among MMT clinic attendants was decreasing since 2009 in Dehong prefecture. Those
      who were unemployed, injecting drug users and HIV positive were at higher risk of
      HCV infection.

PMID- 24125602
TI  - [Epidemiological characteristics of hepatitis C in Henan province].
AB  - OBJECTIVE: To understand the epidemiological characteristics of hepatitis C in
      Henan province. METHODS: Multistage sampling was used to investigate a group of 1
      75 year-old general population, living in 30 districts of 18 cities, Henan
      province. Blood samples were collected and tested for anti-HCV and hepatitis C
      virus(HCV), from April to July 2012. RESULTS: 32 203 persons were investigated.
      Among the general population aged 1 to 75 years old, the overall prevalence rates
      of anti-HCV and HCV RNA were 0.64% and 0.35% respectively. The prevalence rates
      of anti-HCV among males and females were 0.60%, and 0.68% respectively, with the
      rates of HCV RNA as 0.37%, and 0.33% respectively. The prevalence rates of anti
      HCV and HCV RNA were increasing with age. The prevalence rates of anti-HCV and
      HCV RNA in urban area were 0.58% and 0.32%, and in rural area as 0.41%, and 0.19%
      respectively. CONCLUSION: After the implementation of comprehensive measures for
      HCV control and prevention, Henan province became low prevalent for HCV
      infection. Our data revealed that the overall prevalence remained low, but the
      epidemic was severe in some geographical regions in Henan province.

PMID- 24125603
TI  - [Risk of obesity-related gene polymorphism on the incidence and durative of
      childhood obesity].
AB  - OBJECTIVE: To examine the impact of single nucleotide polymorphisms(SNPs)in
      obesity-related genes on the incidence and durative of obesity in childhood and
      adolescence. METHODS: Based on the Beijing Child and Adolescent Metabolic
      Syndrome (BCAMS) Study, 780 school children aged 6 to 16 years were followed-up
      in 2010, and assessed for body size parameters. Venipuncture blood samples were
      collected after a 12-hour overnight fast. Genomic DNA was isolated from
      peripheral blood white cells under the salt fractionation method. SNPs were
      genotyped by ABI 5700 real time PCR(FTO rs9939609)and TaqMan Allelic
      Discrimination Assays with the GeneAmp 7900 Sequence Detection System(Applied
      Biosystems,Foster City, CA, USA) (FTO rs6499640, FAIM2 rs7138803,NPC1 rs1805081,
      MC4R rs17782313, BDNF rs6265, GNPDA2 rs10938397). Both overweight and obesity
      were diagnosed by the Chinese age- and sex- specific body mass index(BMI)
      cutoffs. Two independent sample t-test, Chi-square test and multiple logistic
      regression analysis were performed. RESULTS: During the 6 years follow-up period,
      the incidence of obesity in the total sample 8.5%, and 65.1% individuals had
      persisted their obese status. The genotypes of the SNPs except BDNF rs6265 were
      in Hardy-Weinberg equilibrium in each group (P > 0.05). The incidence rates of
      obesity increased with FTO rs9939609 TT,TA and AA genotypes(chi(2) for trend =
      8.030, P < 0.05). In the non-obese sub-cohort, after adjusted for sex, age at the
      initial time of follow up and residential area, when compared with children
      carrying FTO rs9939609 T-allele, a significantly relative risk of obesity was
      observed for children carrying the rs9939609 A-allele(OR = 2.42, 95%CI:1.31-4.47,
      P = 0.005). In the obese sub-cohort, FTO rs9939609 A-allele was significantly
      associated with durative of obesity (OR = 1.72, 95%CI:1.07-2.77, P = 0.026).
      However, no statistical significant associations were seen between other SNPs(FTO
      rs6499640, FAIM2 rs7138803, NPC1 rs1805081, MC4R rs17782313, GNPDA2
      rs10938397)and the incidence or durative of obesity(all P > 0.05). The genetic
      risk score was associated with the risk of occurrence of obesity(OR = 16.42, 95%
      CI:3.59-75.10, P < 0.001) after adjusted for residential area, sex, age at the
      initial time of follow up and baseline BMI. CONCLUSION: We confirmed the
      association of FTO rs9939609 with incidence and durative of obesity in children.
      Early intervention was recommended on the high risk individuals who carrying more
      risk alleles in obesity-related genes.

PMID- 24125604
TI  - [Relation between uric acid and coronary artery calcification:a community-based
      cross-sectional survey among Beijing natural population].
AB  - OBJECTIVE: To investigate the influence of uric acid on coronary artery
      calcification in the natural population in Beijing. METHODS: From April to July
      2012, 903 subjects from the natural population(aged 37-76 years for men, aged 42
      76 years for women)in Xishan community, Beijing, were selected to accept a survey
      on the risk factors of cardiovascular. Blood tests and CT coronary artery calcium
      scans were carried out. RESULTS: At the 1 Quartile(1 Q), 2 to 3 Quartile(2-3
      Q)and 4 Quartile(4 Q)of uric acid levels, the prevalence rates of coronary artery
      calcium were 37.2% , 45.5% , 60.6% (P<0.001) and the coronary artery calcium
      scores were (109.7+/-333.1)AU, (133.9+/-356.9)AU, (200.8+/-459.4) AU (P <
      0.001)respectively. Data from the univariate logistic regression analysis showed
      that with the increase of uric acid, the prevalence rates of coronary artery
      calcium also increased(OR2-3Q = 1.41, 95% CI:1.02-1.95, P = 0.040; OR4Q = 2.60,
      95% CI:1.78-3.80, P < 0.001). However, the relationship between uric acid and
      coronary artery calcium disappeared when using the multivariate logistic
      regression analysis(OR2-3Q = 0.92, 95% CI: 0.60-1.43, P = 0.713;OR4Q = 1.38, 95%
      CI:0.80-2.39, P = 0.247). CONCLUSION: Uric acid did not seem to be an independent
      risk factor for coronary artery calcium, although the prevalence and extent of
      coronary artery calcium increased along with the increasing trend of uric acid.

PMID- 24125605
TI  - [Study on the attitudes toward suicide among university students in Chongqing].
AB  - OBJECTIVE: To explore the attitudes on suicide and their related factors among
      university students in Chongqing. METHODS: A total of 9808 students from 11
      universities in Chongqing, were chosen under stratified cluster random sampling
      method and had completed a questionnaire survey through the Scale of Public
      Attitudes on Suicide(SPAS). RESULTS: Data showed that the scores of university
      students having negative or neutral attitudes towards questions including
      "suicide is not preventable", "suicidal behavior is not controllable or is caused
      by outside forces" and "suicidal behavior can(or is used to)affect the behavior
      of others'" were 34.28+/-16.44, 35.64+/-19.14 and 36.94+/-16.05 respectively. The
      scores of students taking neutral attitude towards questions as:"similarity of
      attempted and completed suicide", "negative attitudes on the behavior or on the
      person him/her self", "positive aspects of suicide and positive feelings about
      suicides"were 47.38+/-22.01, 51.78+/-17.05 and 37.77+/-18.12 respectively but
      70.77+/-17.21 went to the students who had agreed with "suicide is an important
      social/health problem". Factors as gender, nationality, religion, history of
      attempted suicide and suicide exposure to others appeared having had important
      effects on the attitude towards suicide among college students. CONCLUSION: It is
      necessary to consider above mentioned factors when developing related suicide
      crisis intervention strategy.

PMID- 24125606
TI  - [A comparative study on the status of physique in populations in Chengdu and the
      whole nation in 2010].
AB  - OBJECTIVE: To understand the status of physique and variational tendency of
      population in Chengdu, and comparing to the national level, for the purpose of
      providing evidence in improving the body mass among citizens in Chengdu. METHODS:
      Different groups were selected by cluster random sampling method, with a total of
      5603 samples selected. Body shape, physiological and physical skills were
      measured according to the 2010 Workbook of Public Physique Monitoring Program and
      compared to the results from 2010. T test was used. RESULTS: For body shape,
      height and weight of the people in Chengdu were lower than the national average
      levels. Among them, males aged from 45 to 64 years old were 4.0 cm lower, females
      above 40 years old were 2.0 cm lower in height, when comparing to the national
      average levels with differences on weight as 3.5-6.4 kg for men and 1.7-3.2 kg
      for women. The chest, waist and hip circumferences of males were less than the
      national average levels, but showing at matching levels in women. Upper arm and
      abdominal skinfold in men were less than the national average, but the scapular
      skinfold was larger. Scapular skinfold was larger than the national levels, more
      than 7.1 mm in the 30 to 59 year-olds. Skin folds of the upper arm, shoulder and
      scapular in females were larger than the national levels. Citizens in Chengdu and
      the nation showed matching physiological levels. Physical skill of the adults was
      weaker than the national average level but the quality regarding power of
      gripping and time of reaction were superior in the elderly. CONCLUSION: Levels of
      physique mass in Chengdu citizens were, in general, lower than the national
      average level. Elderly appeared having better physical quality, but not in the
      mid-aged adults. Our data suggested that a great effort should be made to improve
      the health of the mid-aged adults.

PMID- 24125607
TI  - [Causation between occupational prolonged standing time during progestation and
      pregnancy related complications].
AB  - OBJECTIVE: To describe the epidemiological characteristics of profession related
      long-standing behavior during preconception and progestation, and to probe the
      relationship between prolonged standing jobs and the common pregnancy related
      complications among pregnant women, in Ma' anshan city,Anhui province. METHODS:
      In this cohort study, subjects who had their first antenatal examination at Ma'
      anshan Maternal and Child Care Centers were recruited under informed consent,
      from October 2008 to October 2010. All the information were collected through
      questionnaires in the first, second and third trimesters respectively. Three
      questionnaires were filled in by subjects under the guidance of healthcare
      takers. RESULTS: In the study, the 75(th) percentile of prolonged-standing times
      were 4.0 h/d and 3.0 h/d respectively in preconception and progestation. The
      characteristics of pregnant women with low social/economic status, prone to be
      involved in stand-long occupation. Results in logistic regression analysis,
      prolonged-standing jobs during preconception was the risk factor of pregnancy
      induced hypertension and severe anemia. The adjusted odds ratios were 2.05
      (95%CI:1.26-3.31) and 1.38(95%CI:1.03-1.85)respectively. CONCLUSION: Prolonged
      standing jobs appeared to be common occupational exposure to and risks of both
      pregnant woman and their fetus. Exposure to these kinds of jobs during
      preconception could increase the risk of pregnancy-induced hypertension and
      severe anemia. In order to promote maternal health programs, all the related
      occupational risk factors should be valued and avoided during preconception and
      pregnancy.

PMID- 24125608
TI  - [Assessment on the short-term impact regarding the community-based interventions
      to improve physical activities in three urban areas of Hangzhou city].
AB  - OBJECTIVE: To evaluate the short-term impact of comprehensive community based
      intervention on physical activity (PA) of adults living in the three urban
      communities of Hangzhou city. METHODS: Within the framework of Community
      Interventions for Health (CIH) Program, a community trial was conducted in two
      urban areas (Xiacheng district and Gongshu district)and an urban area(Xihu
      district)as control, by a parallel comparison and random grouping based quasi
      experimental design. Two independent questionnaire-based surveys of cross
      sectional samples in the intervention and comparison areas were used to assess
      the short-term impact of the intervention program. RESULTS: A total of 2016
      adults at baseline and 2016 adults at follow-up stages, completed the survey,
      including 1016 adults from the intervention areas and 1000 from the comparison
      area. Over the two-year intervention period, the cognitive level on benefits of
      physical activity in the intervention areas were trending downward. The changes
      observed in the comparison area did not show statistical significance.
      Intervention areas showed a statistically significant increase (1204 vs. 1386, P
      = 0.023) in the level of physical activity(metabolic equivalent, MET
      minutes/week)compared with the comparison area(918 vs. 924, P = 0.201). And
      results remained the same after eliminating the possible effects of age factor.
      CONCLUSION: After a two-year intervention, beneficial changes were noted in the
      intervention areas with respect to the level of physical activity. A community
      based intervention program on physical activity seemed feasible and effective in
      the urban areas of Hangzhou.

PMID- 24125609
TI  - [The influence of familial factors on post rabies exposure vaccination in rural
      habitats].
AB  - OBJECTIVE: To understand the current situation of potential exposure to rabies
      among the rural habitats in Hunan province, and to study the impact related to
      familial factors on post rabies exposure vaccination. METHODS: In total, 40
      villages from 20 townships of 4 counties were selected by multistage sampling
      method. Study samples were selected from these villagers and familial basic
      information and vaccination post rabies exposures were recorded through
      questionnaires. Data were statistically analyzed by SPSS 17.0. RESULTS: Among
      3042 villagers from 864 households being surveyed, 124 person-time exposures were
      found from January, 2009 to October, 2010, with a total exposure rate as 4.08%,
      and the annual average exposure rate as 2.33%. Data from univariate analysis
      showed that the rates on post rabies exposure vaccination were statistically
      correlated with the following four factors:knowledge on the score of rabies
      prevention (chi(2) = 8.260, P = 0.042), whether being involved in the new type of
      rural cooperative medical care(P = 0.035), family disposable cash income in the
      year of 2009(chi(2) = 10.831, P = 0.031), distance between the households and the
      health facilities in towns and townships(chi(2) = 9.071, P = 0.033). Results from
      logistic regression analysis indicated that the score of knowledge on rabies
      prevention(O?R = 1.420, 95% CI:1.055-1.905)and the annual disposable cash income
      of the family in 2009(O?R = 1.480, 95% CI:1.044-2.098)were independent factors
      that influencing the rabies vaccination. CONCLUSION: Strengthening the education
      programs on rabies prevention in rural habitats and increasing family income were
      feasible way to increase the rate of rabies vaccination in rural areas of Hunan
      province.

PMID- 24125610
TI  - [Application of the China Infectious Diseases Automated-alert and Response System
      in Guangxi, 2009-2011].
AB  - OBJECTIVE: To analyze and further improvement the application of the China
      Infectious Diseases Automated-alert and Response System (CIDARS) in Guangxi
      Zhuang Autonomous Region. METHODS: Results related to the amount of signal,
      proportion of signal responded, time to signal response, manner of signal
      verification and on each signal of Guangxi in CIDARS from 2009 to 2011 were
      described. Performance was compared between the periods of pre/ post the
      adjustment of parameters in CIDARS on December 10, 2010. RESULTS: A total of 29
      788 signals were generated on 16 infectious diseases in the system in Guangxi.
      100% signals had been responded with the median time to response as 1.5 hours.
      The average amount of signal per county per week was 1.7;with 624
      signals(2.09%)verified as suspected outbreaks preliminarily and 191 outbreaks of
      9 diseases were finally confirmed by further field investigation. The sensitivity
      of CIDARS was 89.25% , and the timeliness of detection was 2.8 d. After adjusting
      the parameter of CIDARS, the number of signals reduced, and the sensitivity and
      timeliness of detection improved for most of the diseases. CONCLUSION: The
      signals of CIDARS were responded timely, and the performance of CIDARS might be
      improved by adjusting the parameters of early-warning model, which helped enhance
      the ability of outbreaks-detection for local public health departments. However
      the current proportion of false positive signals still seemed to be high,
      suggesting that both the methods and parameters should be improved, according to
      the characteristics of different diseases.

PMID- 24125611
TI  - [The application of China Infectious Diseases Automated-alert and Response System
      in Zhejiang province, 2012].
AB  - OBJECTIVE: To analyze and evaluate the application of China Infectious Diseases
      Automated-alert and Response System(CIDARS)in Zhejiang province. METHODS: Data
      through the monitoring program in 2012 was analyzed descriptively and compared
      with the incidence data in the same period as well information related to public
      health emergency events. RESULTS: A total of 14 292 signals were generated on 28
      kinds of infectious diseases in the system, in Zhejiang province. 100% of the
      signals had been responded and the median time to response was 0.81 hours. 123
      signals (0.86%)were preliminarily verified as suspected outbreaks and 33
      outbreaks were finally confirmed by further field investigation, with a positive
      ratio of 0.23% . Information related to regional distribution showed significant
      differences which reflecting a positive correlation between the numbers of
      diseases and the time of early-warning(r = 0. 97, P < 0.01). Distribution of
      information related to different types of diseases was also significantly
      different, showing a positive correlation between the prevalent strength of the
      disease and the amount of information in a specific area(r = 0.80, P < 0.01).
      CONCLUSION: CIDARS had a good performance which could be used to assist the local
      public health institutions on early detection of possible outbreaks at the early
      stage. However, the effectiveness was different for different regions and
      diseases.

PMID- 24125612
TI  - [Economic costs of both overweight and obesity among Chinese urban and rural
      residents, in 2010].
AB  - OBJECTIVE: Using the latest available data to estimate the direct economic burden
      of overweight and obesity in China. METHODS: 'Cost-of-illness' approach was used
      to calculate the costs of five major non-communicable diseases(NCDs)which were
      associated with overweight and obesity. National data from the 2010 Chinese
      Behavioral Risk Factors Surveillance Survey and the 2008 National Health Service
      Survey were used to compute the Population Attributable Risks(PARs) of overweight
      and obesity for each major NCDs. Costs specific to overweight and obesity were
      obtained by multiplying costs of each disease by the PARs for each NCD. RESULTS:
      In 2010, overweight and obesity were imposing a substantial economic burden on
      China, responsible for 42.9% of the medical and non-medical yearly costs of the
      major NCDs in China, with the amount as 90.768 billion RMB. CONCLUSION: The
      economic costs of overweight and obesity increased over the years, accounting for
      4.5% of the national health expenditure. The high economic burden of overweight
      and obesity implied the need to develop and implement policies that addressing
      the behavior-related risk factors and the obese-genic environment, in order to
      curb the NCDs epidemic in China.

PMID- 24125613
TI  - [Fertility rate and the prediction of future population size in Shaanxi
      province].
AB  - OBJECTIVE: To analyze the fertility rate and to estimate the future population
      size of Shaanxi province, based on data from the sixth national population
      census. METHODS: Fertility rate curve was used to analyze the fertility model and
      the abbreviated life table. The actual fertility rate was used as the main way to
      predict the future population size. General fertility rate was analyzed by factor
      analysis approach. RESULTS: The total fertility rate of Shaanxi province was 1.05
      in 2010 while age-specific fertility rate contributed 101.27% to the general
      fertility rate. The expected population sizes would be 38 122 474 in 2015, 38 432
      931 in 2020 and 38 121 904 in 2025 respectively. CONCLUSION: Birthrate would
      become lower and the population size appearing a negative increase in the year
      2020, in Shaanxi province.

PMID- 24125614
TI  - [Genomic sequences of human infection of avian-origin influenza A(H7N9)virus in
      Zhejiang province].
AB  - OBJECTIVE: To analyze the etiology and genomic sequences of human infection of
      avian-origin influenza A(H7N9)virus from Zhejiang province. METHODS: Viral RNA
      was extracted from patients of suspected H7N9 influenza virus infection and real
      time RT-PCR was conducted for detection of viral RNA. All 8 segments of influenza
      virus were amplified by one-step RT-PCR and genomic sequences were assembled
      using the sequencing data. All the currently available HA and NA genes of the
      novel H7N9 virus, some other HAs from H7 subtype and NAs from N9 subtype were
      downloaded from public database for phylogenetic analysis, using the Mega 5.1
      software. Mutations and variations were analyzed, using the genomic sequence
      data. RESULTS: Reactions for influenza type A, subtype H7 and subtype N9 were all
      positive and all the genomic fragments were amplified for sequencing. After
      alignment, sequences were subjected for phylogenetic analysis. The results
      revealed highest homology with A/duck/Zhejiang/12/2011(H7N3)in HA gene and with
      A/wild bird/Korea/ A14/2011(H7N9)in NA gene of the H7N9 influenza virus. All 6
      genes coding for internal proteins shared highest identities with H9N2 avian
      influenza which were circulated in the Chinese mainland, in the last two years.
      The sequenced virus showed Q226L mutation in HA protein, but E627K was not
      presented in PB2 protein of this virus. The E627K mutation was shared by all the
      other novel H7N9 viruses resulted in human infections through analysis on the
      currently available sequences. CONCLUSION: Using the clinical samples, both
      detection of the viral genes and amplification of all 8 segments of the novel
      H7N9 influenza virus were accomplished. High homology of the novel H7N9 influenza
      viruses was observed by phylogenetic test, using the currently available
      sequences. The virus showed Q226L mutation on HA protein but E627K did not
      present on PB2 protein of this virus.

PMID- 24125615
TI  - [Molecular characterization of Vibrio parahaemolyticus collected from human
      infections in Shenzhen, between 2002 and 2008].
AB  - OBJECTIVE: To determine the occurrence and distribution of specific clones of
      pathogenic Vibrio parahaemolyticus(VP)isolated in Shenzhen and to assess the
      relationship between serotype O3:K6 and the globally distributed pandemic clone.
      METHODS: A total of 1005 VPs isolated from diarrhea patients in 2002-2008 were
      sero-typed. Real-time PCR was used to detect the virulence genes tlh, toxR, tdh,
      trh and orf8 in 281 isolates from 68 different serotypes. The main serotypes were
      typed by pulsed field gel electrophoresis(PFGE). Strains with dominant serotypes
      and PFGE patterns were assayed by GS-PCR and toxRS sequencing for the
      identification of pandemic clone. Multilocus sequence typing(MLST)analysis was
      reserved for exemplary 41 O3 : K6 and O1 : K25 isolates. RESULTS: Seventy-nine
      serotypes were observed among the 1005 isolates, including O3 : K6(57.9%), O4 :
      K8(8.16%), O1 : KUT(5.87%), O1 : K25(5.27%), O4 : K68(1.39%), O1 : K56(1.39%) and
      O9 : K44(0.99%). Most of the strains(99.36%)showed PCR positive to tlh, toxR, and
      tdh but eleven strains were tdh negative. MLST showed that all the 36 O3 : K6
      isolates belonged to ST3 and all the 5 O4 : K8 strains were ST189. These results
      matched the description of the pandemic VP clone. CONCLUSION: A recognizable
      burden of diarrheal illness caused by VP had been seen in Shenzhen. Results from
      serotyping indicated that although there existing a large variety of diversities,
      the dominant serotype appeared to be O3 : K6. VP isolates identified in Shenzhen
      mainly showed as tdh positive but trh negative, in consistent with the current
      pandemic O3 : K6 clone. The pandemic O3 : K6 clone did appear to co-exist with
      other clones of O3 : K6, as well as O4 : K8,O1 : K25. Potential outbreak of VP
      could be monitored through the laboratory-based surveillance programs, suggesting
      that the strategies related to prevention and control of VP should be prioritized
      in Shenzhen.

PMID- 24125616
TI  - [Assessment and application of a molecular diagnostic method on the detection of
      four types of diarrheagenic Escherichia coli].
AB  - OBJECTIVE: To establish and evaluate a molecular diagnostic method for routine
      monitoring of four types of diarrheagenic Escherichia (E.) coli (DEC)and to study
      the distribution of four types of DEC isolated from diarrheal patients in
      Shanghai. METHODS: DEC-PCR standard operation procedure(SOP)had been developed
      for DEC detection and isolation, using the Statens Serum Institute (SSI) DEC PCR
      kits with multiplex PCR technique after verification tests on reference strains.
      Diarrhea specimens from 3 clinical hospitals in Shanghai were tested from June to
      September, 2012. RESULTS: Specificity of the PCR kit was 100% by verification on
      the 26 DEC reference strains. A total number of 218 DEC isolates, including 181
      fermented lactose and 37 unfermented lactose were identified from the 1887 stool
      specimens of diarrhea patients, with positive rate as 11.6%. The most common
      pathogen(54.1%, 118/218)was enteropathogenic E. coli(EPEC), followed by
      enterotoxigenic E. coli(ETEC, 41.3%, 90/218), enteroinvasive E. coli (EIEC, 4.1%,
      9/ 218) and Shigatoxin-producing E. coli(STEC, 0.5%, 1/218)in addition to 18
      Shigella isolates. ETEC dominated in diarrhea patients with foreign residency, as
      well as 1/3 were perinatal stage of neonatal ETEC of all diarrhea cases under the
      age of 5, while EPEC dominated in the Chinese diarrhea patients especially among
      young kids under the age of 2. CONCLUSION: Data was reliable after assessment on
      this molecular diagnostics and seperation procedures used for the routine
      monitoring on four types of DEC, while the diagnosis and reference ability of DEC
      regarding the laboratories net-working on food-borne pathogens need to be built
      up and improved.

PMID- 24125617
TI  - [Correlation between pulsed-field gel electrophoresis profiles and Salmonella
      serotypes].
AB  - OBJECTIVE: To analyze the relationship between pulsed-field gel electrophoresis
      (PFGE)subtyping and serotyping of Salmonella(S.). METHODS: PFGE was performed and
      profiles were analyzed on 1230 Salmonella isolates which comprising the top five
      serotypes including Typhimurium, Enteritidis, Derby, Agona and Senftenberg
      identified in China. The potential predictive relationship between PFGE banding
      patterns and particular serotypes was compared and the discriminatory consensus
      band class markers of individual serotypes were identified. RESULTS: Among all
      the 1230 Salmonella strains, 1149 strains were found assistant with serotyping
      through PFGE cluster analysis, providing the matching accuracy reaching 93.4%.
      For the five serotypes, the positive prediction rate appeared more than 90.0% and
      the negative prediction rate was over 95.0% on serotype cluster prediction.
      CONCLUSION: Results presented in this study were representatives of the top 5
      Salmonella serovars, showing that PFGE cluster analysis could provide clues to
      identity and confirmation of serotypes.

PMID- 24125618
TI  - [Relationship between baseline heart rate and all-cause death in general
      population].
AB  - OBJECTIVE: To investigate the relationship between baseline heart rate(HR) and
      all-cause death(ACD)in general population. METHODS: 93 716 workers with heart
      rate between 40 bpm/min-120 bpm/min and without histories of stroke were selected
      from the '2006-2007 health examination records' in Kailuan and completed the
      electrocardiogram exam. Related information were also gathered. These subjects
      were followed up from July 2006 to December 2010, with the mean time of follow-up
      as 47.5+/-4.3 months. During the follow-up period, the occurrence of all-cause
      death was observed every half a year. RESULTS: (1)The lowest cumulative mortality
      rate was 1.61% in the group with 60-69 bpm/min. The lowest cumulative mortality
      rate was 1.78% in the group of 60-69 bpm/min in men. There was no death events
      observed in women with less than 50 bpm/min and the lowest cumulative mortality
      rate was 0.60% in the group of 80-89 bpm/min in women. (2)Data from Cox
      proportional hazard regression analysis showed that the RR(95%CI)of cumulative
      mortality rates in general population were 1.187 (1.039-1.336), 1.392(1.185
      1.636), 1.733(1.404-2.139)and 2.716 (2.171-3.398)in the groups of 70-79, 80-89,
      90-99 and >=100 bpm/min, respectively. The RRs (95% CI) of cumulative mortality
      in men were 1.227(1.067-1.410), 1.481(1.254-1.750), 1.754 (1.406-2.188)and 2.831
      (2.245-3.571) respectively. In women, when comparing with the group of 80-89
      bpm/min, the RRs (95%CI)of all-cause death were 0.671(0.568-0.793), 0.825(0.703
      0.970) and 1.925 (1.512-2.453)respectively in the groups of 60-69, 70-79 and
      >=100 bpm/min. CONCLUSION: When HR exceeding >=70 bpm/min, the increase of HR
      would also increase the rate of ACD. Results of our study also showed a J-shaped
      curve relation between HR and mortality.

PMID- 24125619
TI  - [Study on the screening program and risk factors of carotid artery stenosis with
      coronary artery disease].
AB  - OBJECTIVE: The purpose of this research project was to evaluate the relationship
      and risk factors between coronary artery disease and carotid artery
      stenosis(CAS), screened by duplex ultra-sonography. METHODS: 1339 patients with
      coronary artery disease were enrolled into this study. All patients performed
      carotid duplex ultra-sonography during hospitalization after coronary artery
      angiography. RESULTS: The overall incidence of CAS was 11.8%(158/1339). Patients
      under older age and having history of stroke, the incidence rates were higher
      than other groups(P < 0.01, P = 0.02). The incidence of CAS in patients with
      multi-vessel lesions was higher than those of diseases involved in one
      vessel(chi(2) = 37.482, P < 0.01). CAS patients having left side major diseases,
      the incidence was higher than those of others(chi(2) = 38.93, P < 0.01). By
      multivariable logistic regression analysis, factors as:older age, having had
      history of stroke, with left side major disease and multivessel lesions etc.
      appeared to be independent predictors of CAS, respectively. CONCLUSION: Patients
      with coronary artery diseases had higher prevalence rates for CAS when suffering
      from multi-vessel lesions or stenosis of left major stem. Factors as being
      elderly, having history of cerebro-vascular diseases were independent predictors
      of CAS in patients with coronary artery diseases.

PMID- 24125620
TI  - [Influence of levocarnitine on heart function and endocrine among patients with
      heart failure].
AB  - OBJECTIVE: To observe the efficacy of levocarnitine in treating elderly patients
      with chronic heart failure and to explore its impact on cardiac function and
      endocrine. METHODS: 120 elderly patients with chronic heart failure were randomly
      divided into observation and control groups, with 60 cases of each. Patients in
      the control group were given conventional anti-heart failure drugs, and those in
      the observation group were given 3 g levocarnitine within 250 ml normal saline
      for intravenous infusion added to what had been given to the control group.
      Efficacy of the two groups was observed after 15 days. RESULTS: The total
      effective rate in observation group was 95.0% , significantly higher than in the
      control group(83.3%), with statistically significant difference(chi(2) = 4.227, P
      < 0.05). After treatment, indicators as LVEDD, LVESD and LVESV in the observation
      group were significantly lower than those in the control group, with
      statistically significant differences(t = 2.256, 2.335, 2.277, P < 0.05). The
      LVEF values were significantly higher than in the control group after treatment,
      with statistically significant difference(t = 2.364, P < 0.05). Serum NT-pro-BNP,
      creatinine and cystatin C values in the observation group after treatment
      appeared significant reduction, when compared to the control group, and the
      difference was statistically significant(t = 2.339, 2.289, 2.315, P < 0.05).
      CONCLUSION: Levocarnitine could significantly improve the cardiac function, and
      reduce the levels of serum NT-pro-BNP, creatinine and cystatin C. Our results
      suggested that it was worthwhile to promote large-scale clinical trials of this
      kind.

PMID- 24125621
TI  - [Application of gene-based logistic kernel-machine regression model on studies
      related to the genome-wide association].
AB  - To explore the gene-based logistic kernel-machine regression model and its
      application in genome-wide association study(GWAS). Using the simulated genome
      wide single-nucleotide polymorphism(SNPs)genotypes data, we proposed a practical
      statistical analysis strategy-named 'the logistic kernel-machine regression
      model', based on the gene levels to assess the association between genetic
      variations and complex diseases. The results from simulation showed that the P
      value of genes in related diseases was the smallest among all the genes. The
      results of simulation indicated that not only it could borrow information from
      different SNPs that were grouped in genes and reducing the degree of freedom
      through hypothesis testing, but could also incorporate the covariate effects and
      the complex SNPs interactions. The gene-based logistic kernel-machine regression
      model seemed to have certain statistical power for testing the association
      between genetic genes and diseases in GWAS.

PMID- 24125622
TI  - [Prevention and control hepatocellular carcinoma in Shanghai during 40 years].

PMID- 24125623
TI  - [Ehrlichia bacteria and ehrlichiosis].

PMID- 24125624
TI  - [Family-based studies on the etiological epidemiology of stroke].

PMID- 24125625
TI  - [Patterns of health care seeking behavior among the suspects of pulmonary
      tuberculosis].

PMID- 24125626
TI  - [Epidemiological evidence on the relationship between selenium and type 2
      diabetes mellitus].

PMID- 24125628
TI  - Impact Factors of Nursing Journals: What Nurses Need to Know.

PMID- 24125627
TI  - Translating science into the next generation meat quality program for Australian
      lamb.
AB  - This paper introduces a series of papers in the form of a special edition that
      reports phenotypic analyses done in parallel with genotypic analyses for the
      Australian Sheep Industry Cooperative Research Centre (Sheep CRC) using data
      generated from the information nucleus flock (INF). This has allowed new
      knowledge to be gained of the genetic, environment and management factors that
      impact on the carcase and eating quality, visual appeal, odour and health
      attributes of Australian lamb meat. The research described involved close
      collaboration with commercial partners across the supply chain in the sire
      breeding as well as the meat processing industries. This approach has enabled
      timely delivery and adoption of research results to industry in an unprecedented
      way and provides a good model for future research. 

PMID- 24125629
TI  - Three cases of sporadic medullary thyroid carcinoma in progression treated with
      sunitinib.

PMID- 24125630
TI  - The thrombotic and arrhythmogenic risks of perioperative NSAIDs.

PMID- 24125631
TI  - Covalent immobilization of mixed proteases, trypsin and chymotrypsin, onto
      modified polyvinyl chloride microspheres.
AB  - A commercially available trypsin-chymotrypsin mixture was covalently immobilized
      onto modified polyvinyl chloride (PVC) microspheres, which were activated by the
      subsequent treatment of PVC microspheres with ethylenediamine and glutaraldehyde.
      The immobilized mixed protease was characterized by FT-IR and SEM analyses.
      Immobilization conditions were optimized by Box-Behnken design and the response
      surface method. The activity of the immobilized mixed protease prepared under
      optimal conditions (pH 6.6, 23  degrees C, 2 h) reached 1341 U/g. Compared with
      the free form, the immobilized enzyme possesses a slightly higher optimal pH
      value and a wider pH-activity profile, superior thermal stability, and a higher
      Km value. Reusability of the immobilized mixed protease indicated that >70% of
      the original activity was retained after having been recycled six times. 

PMID- 24125632
TI  - Molecular events on tooth socket healing in diabetic rabbits.
AB  - Healing of extraction sockets involves complex cellular events such as repair and
      regeneration of tissue. These events are precisely controlled and regulated by
      specific signalling molecules such as transforming growth factor beta (TGF-beta),
      vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP), and
      insulin-like growth factor (IGF), which are well-conserved proteins involved in
      the initial response to injury and repair in soft and hard tissues. We studied 48
      rabbits, which were divided into 3 groups of 16 each: the control group, the
      untreated diabetic group, and the insulin-treated diabetic group. The lower
      incisor of each rabbit was extracted and, after 2, 10, 20, and 30 days of
      healing, the expression of TGFbeta-3, VEGF, IGF-1R, and BMP-4 in the sockets was
      measured immunohistochemically. Rabbits with untreated diabetes expressed less
      TGFbeta-3 than the other groups throughout the healing periods, whereas IGF-1R
      expression was higher than that in the other groups. This increase in IGF-1R
      expression was responsible for increasing the healing time in rabbits in the
      untreated group. The healing of bone in diabetic rabbits that were not treated
      with insulin was prolonged because of a delay in the onset of cell proliferation
      and osteoblast differentiation, and the insulin treatment had a direct effect on
      the expression of TGFbeta-3 and IGF-1R, which accelerated healing of the socket. 

PMID- 24125633
TI  - Anti-stress effects of d-limonene and its metabolite perillyl alcohol.
AB  - Stress is closely linked by its biological mechanisms to inflammation and by its
      consequences to accelerated aging. Stress triggers a hormonal response along the
      hypothalamus-pituitary-adrenal (HPA) axis, which can disrupt the
      ortho/parasympathetic balance essential for a harmonious life. Proper nutrition,
      adequate physical activity, and limiting the harmful influence of stress play
      important roles in avoiding the development of disease and promoting healthy
      aging. d-Limonene, a monoterpene shown to reduce inflammatory parameters in
      several pre-clinical and clinical models, could also produce an anti-stress
      action by altering ortho/parasympathetic parameters as well as central
      neurotransmitter functions. Here we report on a rat model, where a functional
      observational battery (FOB) was performed by submitting animals to non
      pathological stress. d-Limonene or its metabolite perillyl alcohol (POH) were
      administered per os at a dose of 10 mg/kg. FOB tests were performed 1 hr before
      gavage and then at 60, 120, and 180 min. These tests confirmed the stressed
      status of control rats fed vehicle. Conversely, a series of parameters were
      significantly less disturbed in treated rats, who retained a better activity and
      displayed less signs of stress. These effects were more pronounced and sustained
      after ingestion of d-limonene than POH, suggesting the role of endogeneous
      metabolization of the terpene. These studies show that d-limonene exerts, through
      its metabolite POH, a significant anti-stress action measurable by behavioral and
      physiologic parameters under the influence of the nervous system. In addition to
      its anti-inflammatory effects, a beneficial role as an anti-stress substance
      could thus be claimed for d-limonene used as a dietary supplement.

PMID- 24125634
TI  - Nationwide laboratory-based surveillance of invasive beta-haemolytic streptococci
      in Denmark from 2005 to 2011.
AB  - The aim of this work was to describe national surveillance of invasive beta
      haemolytic streptococci (BHS) in Denmark and to report overall trends and major
      findings by groups and types of BHS causing laboratory-confirmed disease from
      2005 to 2011. A total of 3063 BHS isolates were received from 2872 patients.
      Based on confirmed cases the overall annual incidence increased from 6.2 to 8.9
      per 100 000 persons between 2005 and 2011. In 2011 the incidences of group A, B,
      C and G streptococci were 3.1, 2.3, 0.9 and 2.6 per 100 000 persons,
      respectively. An increase was observed for all groups of BHS, but in particular
      for group G in men above 65 years of age. Among group A streptococci (GAS), five
      T-types (1, 28,12, 3,13,B3264 and B3264) represented 71% and five emm-types (1,
      28, 3, 89 and 12) 76% of all isolates. Among group B streptococci (GBS) four
      types (III, Ia, V, Ib) represented 79% of the isolates. Potential coverage for
      future vaccines against GAS and GBS disease was 76% compared with the 26-valent
      GAS vaccine and 89% based on GBS serotypes Ia, Ib, II, III and V. The number of
      reported cases of invasive BHS disease increased in Denmark from 2005 to 2011.
      Nationwide laboratory-based surveillance of BHS is required to monitor
      epidemiological changes, explore potential outbreaks and determine potential
      vaccine coverage.

PMID- 24125635
TI  - Valorization of artichoke wastewaters by integrated membrane process.
AB  - In this work an integrated membrane system was developed on laboratory scale to
      fractionate artichoke wastewaters. In particular, a preliminary ultrafiltration
      (UF) step, based on the use of hollow fibre membranes, was investigated to remove
      suspended solids from an artichoke extract. The clarified solution was then
      submitted to a nanofiltration (NF) step. Two different 2.5 * 21 in. spiral-wound
      membranes (Desal DL and NP030) with different properties were investigated. Both
      membranes showed a high rejection towards the phenolic compounds analysed
      (chlorogenic acid, cynarin and apigenin-7-O-glucoside) and, consequently, towards
      the total antioxidant activity (TAA). On the other hand, the Desal DL membrane
      was characterized by a high rejection towards sugar compounds (glucose, fructose
      and sucrose) (100%) when compared with the NP030 membrane (4.02%). The
      performance of selected membranes in terms of permeate flux, fouling index and
      water permeability recovery was also evaluated. On the base of experimental
      results, an integrated membrane process for the fractionation of artichoke
      wastewaters was proposed. This conceptual process design permitted to obtain
      different valuable products: a retentate fraction (from the NP030 membrane)
      enriched in phenolic compounds suitable for nutraceutical, cosmeceutical or food
      application; a retentate fraction (from the Desal DL membrane), enriched in sugar
      compounds, of interest for food applications; a clear permeate (from the Desal DL
      membrane) which can be reused as process water or for membrane cleaning.

PMID- 24125636
TI  - Tracking the emergence of high affinity aptamers for rhVEGF165 during capillary
      electrophoresis-systematic evolution of ligands by exponential enrichment using
      high throughput sequencing.
AB  - Capillary electrophoresis-systematic evolution of ligands by exponential
      enrichment (CE-SELEX) is a powerful technique for isolating aptamers for various
      targets, from large proteins to small peptides with molecular weights of several
      kilodaltons. One of the unique characteristics of CE-SELEX is the relatively high
      heterogeneity of the ssDNA pools that remains even after multiple rounds of
      selection. Enriched sequences or highly abundant oligonucleotide motifs are
      rarely reported in CE-SELEX studies. In this work, we employed 454 pyrosequencing
      to profile the evolution of an oligonucleotide pool through multiple rounds of CE
      SELEX selection against the target recombinant human vascular endothelial growth
      factor 165 (rhVEGF165). High throughput sequencing allowed up to 3 * 10(4)
      sequences to be obtained from each selected pool and compared to the unselected
      library. Remarkably, the highest abundance contiguous sequence (contig) was only
      present in 0.8% of sequences even after four rounds of selection. Closer analyses
      of the most abundant contigs, the top 1000 oligonucleotide fragments, and even
      the eight original FASTA files showed no evidence of prevailing motifs in the
      selected pools. The sequencing results also provided insight into why many CE
      SELEX selections obtain pools with reduced affinities after many rounds of
      selection (typically >4). Preferential amplification of a particular short
      polymerase chain reaction (PCR) product allowed this nonbinding sequence to
      overtake the pool in later rounds of selection suggesting that further refinement
      of primer design or amplification optimization is necessary. High affinity
      aptamers with 10(-8) M dissociation constants for rhVEGF165 were identified. The
      affinities of the higher abundance contigs were compared with aptamers randomly
      chosen from the final selection pool using affinity capillary electrophoresis
      (ACE) and fluorescence polarization (FP). No statistical difference in affinity
      between the higher abundance contigs and the randomly chosen aptamers was
      observed, supporting the premise that CE-SELEX selects a uniquely heterogeneous
      pool of high affinity aptamers. 

PMID- 24125637
TI  - Valvular heart disease: classic teaching and emerging paradigms.
AB  - Valvular heart disease is both prevalent and increases with age. The final
      pathway of valvular disease is heart failure and sometimes sudden death, so
      clinicians must identify and treat it before these endpoints occur. Noninvasive
      diagnostic modalities such as echocardiography, exercise tolerance testing, and
      cardiac magnetic resonance provide additional quantitative, qualitative, and
      prognostic data. Studies have elucidated predictors of disease progression and
      potential medical therapies, but the niche of valvular disease has benefited
      relatively less from randomized controlled clinical trials than other
      cardiovascular disease fields. New invasive techniques like transcatheter valve
      replacement offer hope for high-risk operative candidates. We review classic
      teaching with current guidelines and emphasize recent advances in disease
      management.

PMID- 24125638
TI  - Practicing 'check the box' medicine.

PMID- 24125640
TI  - Annotation of the pearl oyster genome.
AB  - The initial, manual annotation analysis of the pearl oyster genome is reported in
      the present issue of Zoological Science. Contributors represent a wide array of
      research fields, including bioinformatics, molecular and cellular biology,
      fisheries science, biochemistry, biomineralogy, molluscan biology, evolutionary
      and developmental biology, and paleobiology, reflecting the pearl oyster's broad
      biological and economic importance. The annotated pearl oyster genome paves the
      way for future studies in diverse areas including pearl aquaculture,
      biomineralization, and lophotrochozoan biology. 

PMID- 24125641
TI  - The importance of total genome databases in research on Akoya pearl oyster.
AB  - Pearl is the most valuable form of gem made by organisms and its beauty has been
      considered attractive and precious by people all over the world. Pearl oyster
      aquaculture system, in which a graft from the mantle pallium is transplanted with
      a nucleus into mother pearl oysters, is currently conducted at the industrial
      level. However, it is unclear what molecular mechanisms are involved in this
      system of pearl formation, which produces brilliant and beautiful nacreous
      layers. Since it takes long time to look for the proteins and genes possibly
      participating in the molluskan shell formation, another sophisticated strategy
      has been expected to screen candidate genes. One breakthrough in the latter area
      was the development of next-generation sequencing (NGS) in place of the automated
      Sanger method, the first generation sequencing technique. Using NGS, expressed
      sequence tag (EST) libraries were constructed from pallial mantle and pearl sac,
      which form the nacreous layer, and from the mantle edge, which forms the
      prismatic layer in the Akoya pearl oyster Pinctada fucata. Subsequently, the
      total genome sequence of the Akoya pearl oyster was analyzed. This database,
      together with the EST database mentioned above, is useful for identifying genes
      responsible for superior phenotype characters for pearl oyster aquaculture such
      as fast growth, disease resistance, easy domestication, and ability to produce
      high quality pearls. Subsequent marker-assisted breeding of the Akoya pearl
      oyster should establish strains with superior genotypes, producing even higher
      quality Akoya pearls. 

PMID- 24125639
TI  - Body mass index, waist circumference, physical activity, and risk of hearing loss
      in women.
AB  - BACKGROUND: Acquired hearing loss is highly prevalent, but prospective data on
      potentially modifiable risk factors are limited. In cross-sectional studies,
      higher body mass index (BMI), larger waist circumference, and lower physical
      activity have been associated with poorer hearing, but these have not been
      examined prospectively. METHODS: We examined the independent associations between
      BMI, waist circumference, and physical activity, and self-reported hearing loss
      in 68,421 women in the Nurses' Health Study II from 1989 to 2009. Baseline and
      updated information on BMI, waist circumference, and physical activity was
      obtained from biennial questionnaires. RESULTS: After more than 1.1 million
      person-years of follow-up, 11,286 cases of hearing loss were reported to have
      occurred. Higher BMI and larger waist circumference were associated with
      increased risk of hearing loss. Compared with women with BMI <25 kg/m(2), the
      multivariate-adjusted relative risk (RR) for women with BMI >= 40 was 1.25 (95%
      confidence interval [CI], 1.14-1.37). Compared with women with waist
      circumference <71 cm, the multivariate-adjusted RR for waist circumference >88 cm
      was 1.27 (95% CI, 1.17-1.38). Higher physical activity was related inversely to
      risk; compared with women in the lowest quintile of physical activity, the
      multivariate-adjusted RR for women in the highest quintile was 0.83 (95% CI, 0.78
      0.88). Walking 2 hours per week or more was associated inversely with risk.
      Simultaneous adjustment for BMI, waist circumference, and physical activity
      slightly attenuated the associations but they remained statistically significant.
      CONCLUSIONS: Higher BMI and larger waist circumference are associated with
      increased risk, and higher physical activity is associated with reduced risk of
      hearing loss in women. These findings provide evidence that maintaining healthy
      weight and staying physically active, potentially modifiable lifestyle factors,
      may help reduce the risk of hearing loss.

PMID- 24125642
TI  - A history of the cultured pearl industry.
AB  - During the 18th and 19th centuries, studies of how pearls are formed were
      conducted mainly in Europe. The subsequent pearl culturing experiments conducted
      worldwide in the early 20th century, however, failed to develop into a pearl
      industry. In Japan, however, Kokichi Mikimoto succeeded in culturing blister
      pearls in 1893 under the guidance of Kakichi Mitsukuri, a professor at Tokyo
      Imperial University (now the University of Tokyo) and the first director of the
      Misaki Marine Biological Station, Graduate School of Science, University of
      Tokyo. This success and subsequent developments laid the foundation for the pearl
      farming industry, developed new demand for cultured pearls in the European
      jewelry market, and initiated the full-scale industrialization of pearl
      culturing. In addition, research at the Misaki Marine Biological Station resulted
      in noteworthy advances in the scientific study of pearl formation. Today, pearls
      are cultured worldwide, utilizing a variety of pearl oysters. The pearl farming
      industry, with its unique origins in Japan, has grown into a global industry.
      Recently, the introduction of genome analysis has allowed cultured pearl research
      to make rapid progress worldwide in such areas as the dynamics of mother-of-pearl
      layer formation and biomineralization. This signals another new era in the study
      of pearls. 

PMID- 24125643
TI  - Initiating the mollusk genomics annotation community: toward creating the
      complete curated gene-set of the Japanese Pearl Oyster, Pinctada fucata.
AB  - The genome sequence of the Japanese pearl oyster, the first draft genome from a
      mollusk, was published in February 2012. In order to curate the draft genome
      assemblies and annotate the predicted gene models, two annotation Jamborees were
      held in Okinawa and Tokyo. To date, 761 genes have been surveyed and curated. A
      preparatory meeting and a debriefing were held at the Misaki Marine Biological
      Station before and after the Jamborees. These four events, in conjunction with
      the sequence-decoding project, have facilitated the first series of gene
      annotations. Genome annotators among the Jamboree participants added 22
      functional categories to the annotation system to date. Of these, 17 are included
      in Generic Gene Ontology. The other five categories are specific to molluskan
      biology, such as "Byssus Formation" and "Shell Formation", including
      Biomineralization and Acidic Proteins. A total of 731 genes from our latest
      version of gene models are annotated and classified into these 22 categories. The
      resulting data will serve as a useful reference for future genomic analyses of
      this species as well as comparative analyses among mollusks. 

PMID- 24125644
TI  - MarinegenomicsDB: an integrated genome viewer for community-based annotation of
      genomes.
AB  - We constructed a web-based genome annotation platform, MarinegenomicsDB, to
      integrate genome data from various marine organisms including the pearl oyster
      Pinctada fucata and the coral Acropora digitifera. This newly developed viewer
      application provides open access to published data and a user-friendly
      environment for community-based manual gene annotation. Development on a flexible
      framework enables easy expansion of the website on demand. To date, more than
      2000 genes have been annotated using this system. In the future, the website will
      be expanded to host a wider variety of data, more species, and different types of
      genome-wide analyses. The website is available at the following URL:
      http://marinegenomics.oist.jp.

PMID- 24125645
TI  - The diversity of shell matrix proteins: genome-wide investigation of the pearl
      oyster, Pinctada fucata.
AB  - In molluscs, shell matrix proteins are associated with biomineralization, a
      biologically controlled process that involves nucleation and growth of calcium
      carbonate crystals. Identification and characterization of shell matrix proteins
      are important for better understanding of the adaptive radiation of a large
      variety of molluscs. We searched the draft genome sequence of the pearl oyster
      Pinctada fucata and annotated 30 different kinds of shell matrix proteins. Of
      these, we could identified Perlucin, ependymin-related protein and SPARC as
      common genes shared by bivalves and gastropods; however, most gastropod shell
      matrix proteins were not found in the P. fucata genome. Glycinerich proteins were
      conserved in the genus Pinctada. Another important finding with regard to these
      annotated genes was that numerous shell matrix proteins are encoded by more than
      one gene; e.g., three ACCBP-like proteins, three CaLPs, five chitin synthase-like
      proteins, two N16 proteins (pearlins), 10 N19 proteins, two nacreins, four Pifs,
      nine shematrins, two prismalin-14 proteins, and 21 tyrosinases. This diversity of
      shell matrix proteins may be implicated in the morphological diversity of mollusc
      shells. The annotated genes reported here can be searched in P. fucata gene
      models version 1.1 and genome assembly version 1.0 (
      http://marinegenomics.oist.jp/pinctada_fucata ). These genes should provide a
      useful resource for studies of the genetic basis of biomineralization and
      evaluation of the role of shell matrix proteins as an evolutionary toolkit among
      the molluscs. 

PMID- 24125646
TI  - Genome-wide survey of genes encoding muscle proteins in the pearl oyster,
      Pinctada fucata.
AB  - The mechanisms of contraction of molluscan striated and smooth muscles differ
      from those in vertebrates. Molluscan striated muscles adopt a myosin-linked
      regulation, unlike vertebrates. Smooth muscles in these species show a unique
      form of contraction, in which the tension is maintained for a long time with
      little energy consumption, called catch. The available gene information is
      insufficient to elucidate the mechanism of contraction of molluscan muscles at
      the molecular level. BLAST searching was thus used to annotate genes encoding
      proteins related to muscle contraction in the completely determined genome of the
      pearl oyster Pinctada fucata using partial nucleotide sequences obtained by 3'
      RACE. We identified genes that encode components of the thick-filament, such as
      myosin heavy chain, myosin essential and regulatory light chains, paramyosin and
      twitchin; of the thin-filament, such as actin, tropomyosin, troponin-T, troponin
      I, troponin-C and calponin; and the PKA catalytic subunit, which is a key player
      in the regulation of catch contraction. The analysis indicated that isoforms of
      myosin heavy chain, paramyosin, and calponin are produced by alternative
      splicing. 

PMID- 24125647
TI  - Reproduction-related genes in the pearl oyster genome.
AB  - Molluscan reproduction has been a target of biological research because of the
      various reproductive strategies that have evolved in this phylum. It has also
      been studied for the development of fisheries technologies, particularly
      aquaculture. Although fundamental processes of reproduction in other phyla, such
      as vertebrates and arthropods, have been well studied, information on the
      molecular mechanisms of molluscan reproduction remains limited. The recently
      released draft genome of the pearl oyster Pinctada fucata provides a novel and
      powerful platform for obtaining structural information on the genes and proteins
      involved in bivalve reproduction. In the present study, we analyzed the pearl
      oyster draft genome to screen reproduction-related genes. Analysis was mainly
      conducted for genes reported from other molluscs for encoding orthologs of
      reproduction-related proteins in other phyla. The gene search in the P. fucata
      gene models (version 1.1) and genome assembly (version 1.0) were performed using
      Genome Browser and BLAST software. The obtained gene models were then BLASTP
      searched against a public database to confirm the best-hit sequences. As a
      result, more than 40 gene models were identified with high accuracy to encode
      reproduction-related genes reported for P. fucata and other molluscs. These
      include vasa, nanos, doublesex- and mab-3-related transcription factor, 5
      hydroxytryptamine (5-HT) receptors, vitellogenin, estrogen receptor, and others.
      The set of reproduction-related genes of P. fucata identified in the present
      study constitute a new tool for research on bivalve reproduction at the molecular
      level. 

PMID- 24125648
TI  - A genome-wide survey of genes encoding transcription factors in the Japanese
      pearl oyster, Pinctada fucata: I. homeobox genes.
AB  - Homeobox genes are involved in various aspects of the development of
      multicellular animals, including anterior-posterior patterning of the body plan.
      We performed a genomic survey of homeobox genes in the Japanese pearl oyster,
      Pinctada fucata, and annotated 92 homeobox-containing genes and five homeobox
      less Pax genes. This species possesses 10 or 11 Hox genes. We annotated another
      homeobox genes that cover 77 out of the 111 gene families identified in the
      amphioxus genome. Investigation of these repertoires of homeobox genes will shed
      new light on the comparatively less well-understood lophotrochozoan development. 

PMID- 24125649
TI  - A genome-wide survey of genes encoding transcription factors in Japanese pearl
      oyster Pinctada fucata: II. Tbx, Fox, Ets, HMG, NFkappaB, bZIP, and C2H2 zinc
      fingers.
AB  - To gain a better understanding of molluscan development and its relation to the
      evolution of their unique body plan, we performed a genomic survey of genes
      encoding transcription factors, such as Tbx, Fox, Ets, HMG, NFkappaB, bZIP, and
      C2H2 zinc finger proteins in the Japanese pearl oyster, Pinctada fucata. We
      annotated 133 transcription factor genes. Together with the orthologs of known
      deuterostome genes, we found several orphan genes in each class of transcription
      factor. Some possessed clear orthologs in other species of lophotrochozoans,
      while no counterpart genes were found in the deuterostomes or ecdysozoans. These
      observations suggest that a number of transcription factor genes are unique to
      lophotrochozoans, and thus additional research frontiers remain to be explored
      with regard to such transcription factors. 

PMID- 24125650
TI  - Evolutionary aspects of variability in bHLH orthologous families: insights from
      the pearl oyster, Pinctada fucata.
AB  - Basic helix-loop-helix (bHLH) transcription factors play significant roles in
      multiple biological processes in metazoan cells. In recent work, we showed that
      three orthologous HLH families, pearl, amber, and peridot, have apparently been
      lost in the Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens
      lineages. To further address the gain and loss of bHLH proteins during bilaterian
      evolution, we examined the genome of the pearl oyster, Pinctada fucata, which has
      recently been sequenced. We characterized the putative full set 65 bHLH genes and
      showed that genes previously categorized into the orthologous family PTFb,
      actually fall into two distinct orthologous families, 48-related-1 and 48-related
      2. We also identified a novel orthologous family, clockwork orange. Based on
      these newly identified orthologous family members and on orphan bHLH factors, we
      propose that genes encoding bHLH factors in bilaterians are not as evolutionarily
      stable as previously thought. 

PMID- 24125653
TI  - Poly-L-lysine increases the ex vivo expansion and erythroid differentiation of
      human hematopoietic stem cells, as well as erythroid enucleation efficacy.
AB  - Hematopoietic stem cells (HSCs) are continuously stimulated by physical
      interactions with bone marrow or umbilical cord niches as well as by chemical
      factors found within these niches. The niche can be mimicked by modification of
      the cytokine composition, elasticity, topography, and/or charge. This work
      employed cell culture plates coated with several concentrations of poly-L-lysine
      (PLL), a positively charged synthetic amino-acid chain. Culture substrates that
      employed relatively high initial coating concentrations of PLL significantly
      increased the total number of HSCs during ex vivo expansion of CD34(+) cells, as
      well as erythroid differentiation. Furthermore, the 0.01% PLL substrate
      stimulated enucleation of erythroid cells, leaving behind a number of extruded
      nuclei at the bottom of the culture plate, followed by an increase in the number
      of erythrocytes. Thus, PLL will likely prove useful to enhance the expansion of
      HSCs and erythroid cells, in addition to the generation of red blood cells. 

PMID- 24125654
TI  - The early diversification history of didelphid marsupials: a window into South
      America's "Splendid Isolation".
AB  - The geological record of South American mammals is spatially biased because
      productive fossil sites are concentrated at high latitudes. As a result, the
      history of mammalian diversification in Amazonia and other tropical biomes is
      largely unknown. Here we report diversification analyses based on a time
      calibrated molecular phylogeny of opossums (Didelphidae), a species-rich clade of
      mostly tropical marsupials descended from a Late Oligocene common ancestor.
      Optimizations of habitat and geography on this phylogeny suggest that (1) basal
      didelphid lineages inhabited South American moist forests; (2) didelphids did not
      diversify in dry-forest habitats until the Late Miocene; and (3) most didelphid
      lineages did not enter North America until the Pliocene. We also summarize
      evidence for an Early- to Middle-Miocene mass extinction event, for which
      alternative causal explanations are discussed. To the best of our knowledge, this
      study provides the first published molecular-phylogenetic evidence for mass
      extinction in any animal clade, and it is the first time that evidence for such
      an event (in any plant or animal taxon) has been tested for statistical
      significance. Potentially falsifying observations that could help discriminate
      between the proposed alternative explanations for didelphid mass extinction may
      be obtainable from diversification analyses of other sympatric mammalian groups. 

PMID- 24125651
TI  - An in-silico genomic survey to annotate genes coding for early development
      relevant signaling molecules in the pearl oyster, Pinctada fucata.
AB  - The pearl oyster Pinctada fucata has great potential as a model system for
      lophotrochozoan developmental biology research. Pinctada fucata is an important
      commercial resource, and a significant body of primary research on this species
      has emphasized its basic aquaculture biology such as larval biology and growth,
      aquaculture, pearl formation and quality improvement, shell formation, and
      biomineralization. Recently, a draft genome sequence of this species was
      published, and many experimental resources are currently being developed, such as
      bioinformatics tools, embryo and larva manipulation methods, gene knockdown
      technique, etc. In this paper, we report the results from our genomic survey
      pertaining to gene families that encode developmental signaling ligands (Fgf,
      Hedgehog, PDGF/VEGF, TGFbeta, and Wnt families). We found most of the
      representative genes of major signaling pathways involved in axial patterning, as
      well as copies of the signaling molecule paralogs. Phylogenetic character mapping
      was used to infer a possible evolutionary scenario of the signaling molecules in
      the protostomes, and to reconstruct possible copy numbers of signaling molecule
      coding genes for the ancestral protostome. Our reconstruction suggests that P.
      fucata retains the ancestral protostome gene complement, providing further
      justifications for the use of this taxon as a model organism for developmental
      genomics research. 

PMID- 24125655
TI  - Pictorial essay: tumours and pseudotumours of sacrum.

PMID- 24125656
TI  - Breakages at YWHAE, FAM22A, and FAM22B loci in uterine angiosarcoma: a case
      report with immunohistochemical and genetic analysis.
AB  - Described herein is the first reported case of a uterine angiosarcoma with
      breakages at three loci, YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22). A 62
      year-old postmenopausal woman was found to have endometrial thickening of her
      uterus. An endometrial biopsy indicated a malignant, spindle cell neoplasm. A
      total hysterectomy with bilateral salpingooophorectomy was performed. Histologic
      examination of the uterine specimen showed a malignant tumor consisting of
      irregular rudimentary vascular channels and solid small nests diffusely
      infiltrating to the middle of the myometrial wall. The tumor cells were
      epithelioid, and displayed eosinophilic cytoplasm and vesicular nuclei in some
      areas of the tumor. Immunohistochemically, the tumor cells showed vascular
      differentiation; they were diffusely positive for CD31 and D2-40 but were
      negative for factor VIII and CD34. In the course of the procedure of differential
      diagnoses, we included fluorescence in situ hybridization analysis for detection
      of a FAM22B-YWHAE fusion gene resulting from t(10;17)(q22;p13), recently reported
      in a series of endometrial stromal sarcoma, and unexpectedly identified breakages
      at three loci, i.e. YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22).
      Collectively, these findings suggest that abnormality in the loci of YWHAE,
      FAM22A and FAM22B, which are known to be associated with oncogenesis of
      endometrial stromal sarcoma, may contribute to the development of uterine
      angiosarcoma. 

PMID- 24125657
TI  - Profiling the molecular mechanism of fullerene cytotoxicity on tumor cells by RNA
      seq.
AB  - The interest on functionalized fullerenes in the field of nanomedicine has seen a
      significant increase in the past decade. However, the different methods employed
      to increase C60 solubility profoundly influence the physicochemical properties
      and the toxicological effects of these compounds, thus complicating the
      evaluation of their toxicity and potential therapeutic use. Here we report a
      whole-transcriptome RNA-seq analysis assessing the effect of two fullerenes (1
      and 2) on gene expression in the human MCF7 cell line. Although these two
      compounds had previously been characterized by in vitro studies as having a
      cytotoxic and null effect respectively, to date the mechanisms at the basis of
      this different behavior and, more in general, at the basis of the effect of most
      fullerene derivatives in living cells are still completely unknown. Our data
      evidence that: (a) fullerene 2 caused a significant, time-dependent alteration of
      gene expression, whereas 1 only had a negligible effect; (b) the biological
      processes mostly influenced over the 48h experimental time course were
      transcription, protein synthesis, cell cycle progression and cell adhesion; (c)
      the gene expression signature of 2-treated cells was strikingly similar to those
      induced by selective inhibitors of mTOR signaling, thus suggesting an effect on
      this pathway for fullerene 2. Our work represents the first approach toward the
      application of RNA-seq to the study of the molecular mechanisms underlying the
      interaction of fullerenes with cellular systems and provides an objective view of
      the feasibility and the safety of these nanomaterials for a medical application. 

PMID- 24125658
TI  - Cloning and molecular characterization of BumaMPs1, a novel metalloproteinases
      from the venom of scorpion Buthus martensi Karsch.
AB  - Scorpion venoms metalloproteinase is involved in a number of important
      biological, physiological and pathophysiological processes. In this work, a
      complete sequence of metalloproteinase was first obtained from venom of scorpion
      Buthus martensi and named as BumaMPs1. BumaMPs1 has 393 amino acid residues
      containing with a molecular mass of 44.53 kDa, showing an isoelectric point of
      5.66. The primary sequence analysis indicated that the BumaMPs1 contains a zinc
      binding motif (HELGHNLGISH), methionine-turn motif (YIM), disintegrin-like domain
      (ETCD) and N-glycosylation site. The multiple alignment of its deduced amino acid
      sequence and those of other metalloproteinase showed a high structural similarly,
      mainly among class reprolysin proteases. The phylogenetic analysis showed early
      divergence and independent evolution of BumaMPs1 from other metalloproteinase. 

PMID- 24125659
TI  - Physiological and antioxidant responses of Medicago sativa-rhizobia symbiosis to
      cyanobacterial toxins (Microcystins) exposure.
AB  - Toxic cyanobacteria in freshwaters can induce potent harmful effects on growth
      and development of plants irrigated with contaminated water. In this study, the
      effect of cyanobacteria extract containing Microcystins (MC) on Medicago sativa
      rhizobia symbiosis was investigated in order to explore plants response through
      biomass production, photosynthetic pigment and antioxidant enzymes analysis:
      Peroxidase (POD), Polyphenoloxidase (PPO) and Catalase (CAT). Alfalfa plants were
      inoculated with two endosymbiotic rhizobial strains: RhOL1 (MC less sensitive
      strain) and RhOL3 (MC more sensitive strain), to evaluate the rhizobial
      contribution on the plant response cultured under cyanobacterial toxins stress.
      The two rhizobia strains were identified as Ensifer meliloti by sequence analysis
      of their rrs and atpD genes. The chronic exposure to MC extract showed shoot,
      root and nodules dry weight decrease, in both symbiosis cultures. The rate of
      decline in plants inoculated with RhOL3 was higher than that in symbiosis with
      RhOL1 mainly at 20 MUg L(-1) of MC. Cyanotoxins also reduced photosynthetic
      pigment content and generated an oxidative stress observed at cellular level.
      POD, PPO and CAT activities were significantly increased in leaves, roots and
      nodules of alfalfa plants exposed to MC. These enzyme activities were higher in
      plants inoculated with RhOL3 especially when alfalfa plants were exposed to 20
      MUg L(-1) of MC. The present paper reports new scientific finding related to the
      behavior of rhizobia-M. sativa associations to MC (Microcystins) for later
      recommendation concerning the possible use of these symbiosis face to crops
      exposure to MC contaminated water irrigation. 

PMID- 24125660
TI  - Epidemiology of snakebite in Europe: comparison of data from the literature and
      case reporting.
AB  - A better assessment of the incidence and mortality due to envenomation should
      improve the antivenom supply and consequently management of snakebites.
      Currently, in most countries, notification of snakebite is insufficient and
      irregular. An alternative is to consider data from the literature to estimate the
      incidence and mortality. The gaps and bias resulting from this method can be
      corrected using a meta-analytic model adjusted with a randomized coefficient,
      which provides an average incidence and mortality taking into account the
      relative weight and representativeness of each sample. The aim of the present
      study is to compare the results of the application of the meta-analytic model
      with the national notifications of snakebites in different European countries. To
      achieve this goal, a questionnaire was sent to health services of all European
      countries asking for the incidence, mortality and some parameters defining the
      population at risk of snakebites in Europe. Notifications were compared with the
      results of a recently published meta-analysis of literature data. Results showed
      an acceptable agreement, although significant differences in the incidence of
      snakebites occurred in some countries. The discussion emphasizes the limitations
      regarding notifications and underlines the potential biases that restrict the
      reliability of data from the literature. Finally, pending reliable notification
      of snakebites in all European countries, analyzing data from the literature is
      likely to be an acceptable and simple solution. 

PMID- 24125661
TI  - Mechanism of in vivo anticoagulant and haemolytic activity by a neutral
      phospholipase A(2) purified from Daboia russelii russelii venom: correlation with
      clinical manifestations in Russell's Viper envenomed patients.
AB  - A 13.0 kDa neutral phospholipase A2 (NEUPHOLIPASE) purified from venom of Daboia
      russelii russelii from eastern India was identified by peptide mass
      fingerprinting analysis. It exerted dose-dependent PLA2, anticoagulant and
      indirect haemolytic activities. NEUPHOLIPASE showed preferential binding followed
      by hydrolysis of phosphatidylserine > phosphatidylcholine >>
      phosphatidylethanolamine. Circular dichroism analysis of NEUPHOLIPASE showed a
      high content of alpha helix (54.6%) followed by beta-turn (29.7%) in its
      secondary structure. Gas-chromatographic analysis of plasma from PLA2-treated
      mice suggested preferential hydrolysis of pro-coagulant phospholipid PS was the
      primary mechanism to account for in vivo anticoagulant effect of NEUPHOLIPASE.
      The NEUPHOLIPASE-treated mice blood showed a significant decrease (p < 0.01) in
      WBC as well as RBC counts with a corresponding decline in Hb content due to
      indirect damage to erythrocyte membranes by plasma phospholipids hydrolysis
      products rather than the direct haemolytic activity of PLA2 under study.
      NEUPHOLIPASE was non-lethal to BALB/c mice, however; it was detrimental to liver
      of treated-mice. Pathological symptoms observed in NEUPHOLIPASE-treated mice were
      correlated with the actual clinical manifestations in Russell's Viper envenomed
      patients from eastern India indicating some contribution of NEUPHOLIPASE in
      Russell's Viper venom induced toxicity and pathogenesis. 

PMID- 24125662
TI  - [Focus on the new type oral anticoagulant therapy on prevention and treatment of
      venous thrombosis].

PMID- 24125663
TI  - [Diagnosis and treatment of deepvenous thrombosis].

PMID- 24125664
TI  - [Value of color Doppler ultrasound in the examination of prethrombotic state].
AB  - OBJECTIVE: To explore the clinical value of color Doppler ultrasound in patients
      with prethrombotic state (PTS). METHODS: From October 2011 to November 2012, a
      total of 201 patients were diagnosed with PTS. There were 95 males and 106
      females with an average age of 52 years (range: 15-78). They were divided into
      intervention and observation groups on the basis of drug intervention. And the
      relevant literatures were reviewed and the images of color Doppler ultrasound
      before and after treatment compared. RESULTS: Before treatment, blood flow peak
      rates of common femoral, popliteal and calf intermuscular veins were (0.16 +/-
      0.03), (0.14 +/- 0.03) and (0.13 +/- 0.02) m/s; after treatment, (0.19 +/- 0.03),
      (0.17 +/- 0.03) and (0.15 +/- 0.01) m/s respectively. The peak flow increased and
      sluggish flow decreased or disappeared in 152 PS patients. It indicated a relief
      or an obvious resolution of hypercoagulable state. And the symptom of lower
      extremity soreness was greatly relieved. Among 49 patients without drug
      intervention, severe full-lumen storm floating occurred in 12 cases. And 8 of
      them suffered deep vein thrombosis within 2 weeks. The incidence of thrombus was
      66.7%. CONCLUSION: Color Doppler ultrasound may detect and assess PTS effectively
      so as to guide effective interventions.

PMID- 24125665
TI  - [Clinical analysis of patients with lower extremity deep venous thrombosis
      complicated with inferior vena cava thrombus].
AB  - OBJECTIVE: To explore the clinical profiles of patients with lower extremity deep
      venous thrombosis (DVT) complicated with inferior vena cava (IVC) thrombus and
      summarize their clinical diagnostic and therapeutic experiences. METHODS: The
      clinical characteristics, diagnosis and treatment of 20 hospitalized patients
      with DVT complicated with inferior vena cava thrombus were analyzed
      retrospectively. RESULTS: All of them were of proximal DVT. There were phlegmasia
      cerulea dolens (n = 3), pulmonary embolism (n = 3) and completely occlusion of
      IVC (n = 5). Clinical manifestations were severe. Retrievable inferior vena cava
      filter (IVCF) was implanted for 17 cases. Catheter-directed thrombolysis (CDT)
      through ipsilateral popliteal vein was applied for 7 cases and systemic
      thrombolysis therapy for 8 cases. The effective rate of thrombolysis for fresh
      IVC thrombus was 100%. Among 5 cases with Cockett Syndrome, 3 cases underwent
      balloon dilatation angioplasty and endovascular stenting of iliac vein. And 17
      IVCFs were retrieved successfully within 3 weeks. IVC thrombus disappeared
      completely in 15 cases. CONCLUSION: Systemic or local thrombolysis with
      protective IVCF is a safe and effective therapy for nonocclusive IVC thrombus in
      DVT. And CDT is recommended for symptomatic occlusive IVC thrombus.

PMID- 24125666
TI  - [Roles of short form-36 health survey scale in the evaluation of quality of life
      in patients with deep vein thrombosis].
AB  - OBJECTIVE: To explore the roles of short form-36 health survey scale in the
      evaluation of deep vein thrombosis (DVT) patients. METHODS: A total of 179 DVT
      patients were recruited from Department of Vascular and Thyroid Surgery, First
      Affiliated Hospital, Xinjiang Medical University from June 2009 to March 2013.
      They were surveyed with short form-36 health survey scale. Then the feasibility,
      reliability, validity, responsibility, ceiling effect and floor effect were
      analyzed. RESULTS: Feasibility analysis: completion time was (10.4 +/- 2.9) min
      and finishing rate 100%. Reliability analysis: all split-half reliability
      coefficients and Cronbach's alpha were above 0.8. all internal consistency
      coefficients were above 0.6. Validity analysis: all Pearson coefficients were
      above 0.6. Two principal components were extracted by factor analysis and it
      accounted for 67.011% of total variance. After maximal variance rotation, two
      common factors were generated. And it was almost the same with the theoretic
      structural assumption of scale. Responsibility analysis: all score of every
      degree at post-treatment were higher than at pre-treatment. And it was
      statistically significant (P < 0.01). Ceiling and floor effects: there was
      remarkable ceiling effect on role physical (RP) and emotional role (RE) (24.81%,
      36.62%). Remarkable floor effect on RP was 31.76%. CONCLUSION: Short form-36
      health survey scale is satisfactory in the evaluation of quality of life among
      DVT patients. But specific items need further improvement.

PMID- 24125667
TI  - [Insertion of double inferior vena cava filter in patients with deep venous
      thromboembolism].
AB  - OBJECTIVE: To explore the characteristic, diagnosis and treatment of deep venous
      thromboembolism (DVT) patients with congenital double inferior vena cava.
      METHODS: Retrospective analyses were conducted for the indications, filter types
      and efficacies of vena cava filter insertion in 7 hospitalized DVT patients with
      congenital double inferior vena at our hospital from 2006 to 2012. RESULTS: All
      of them had definite indications for vena cava filter insertion. Temporary and
      permanent vena caval filters were implanted in one subject while retrievable vena
      caval filters in another five subjects. One retrievable filter was replaced by a
      permanent filter due to excessive thrombus entrapped in filter. Other temporary
      or retrievable filters were extracted successfully. All subjects were prescribed
      postoperatively with oral anticoagulants. The follow-up period was 1-72 months.
      No recurrent DVT or pulmonary embolism occurred. CONCLUSION: The complications of
      double inferior vena cava in DVT subjects are often misdiagnosed due to its low
      incidence rate and a lack of clinical manifestations. Fatal pulmonary embolism
      after implantation may be due to an inappropriate location of filter implant. If
      implanted in a proper position, satisfactory outcomes ensue.

PMID- 24125668
TI  - [Effects of metabolic syndrome on multi-vessel lesions of symptomatic
      intracranial atherosclerosis].
AB  - OBJECTIVE: To explore the effects of metabolic syndrome (MS) on multi-vessel
      lesions of symptomatic intracranial atherosclerosis. METHODS: During April 2009
      and October 2010, a total of 139 consecutive hospitalized patients with
      symptomatic intracranial atherosclerosis were recruited to undergo magnetic
      resonance angiography (MRA) or/and CT angiography (CTA) or/and digital
      subtraction angiography (DSA) to measure the stenotic degree and numbers of
      intracranial atherosclerosis. They were divided into 2 groups according to lesion
      numbers: single and multi-vessel lesions. MS was defined by the criteria of the
      Adult Treatment Panel III to examine the incidences of MS. The risk factors were
      analyzed for multi-vessel lesions of symptomatic intracranial atherosclerosis to
      explore the relationship between MS and multi-vessel lesions. RESULTS: Among
      them, 210 intracranial atherosclerotic lesions were documented. Fifty-nine
      (42.4%) patients had two or more lesions (group with multi-vessel lesions). The
      incidence of MS was 70.5%. The rates of MS in groups of single and multi-vessel
      lesions were 56.3% and 89.8% respectively. And statistical significance existed
      between two groups (P < 0.001). Moreover, the number of MS components increased
      gradually with the number of lesions (P < 0.001). For the analysis of individual
      criteria for MS, only abnormal glycemia was found to be associated with multi
      vessel lesions (P = 0.002). And multiple Logistic regression analysis showed that
      MS was associated with multi-vessel lesions of intracranial atherosclerosis (P =
      0.001). CONCLUSIONS: MS is an independent predictor for multi-vessel lesions of
      intracranial atherosclerosis. And its intervention may be an important preventive
      strategy for intracranial multi-vessel atherosclerosis.

PMID- 24125669
TI  - [Characteristics of prospective memory impairments in patients with severe
      traumatic brain injury during recovery stage].
AB  - OBJECTIVE: To explore the characteristics of time-based prospective memory (TBPM)
      and event-based prospective memory (EBPM) in patients with severe traumatic brain
      injury (TBI) during recovery stage. METHODS: A total of 20 patients with severe
      TBI were recruited along with another 20 age, gender and education-matched
      healthy volunteers. The Chinese version of Cambridge Prospective Memory Test was
      used to assess the TBPM and EBPM characteristics. The TBPM score, EBPM score,
      time monitoring frequency, cue finding frequency, and whether or not the
      participants choose to take notes were recorded and compared between patients and
      controls. RESULTS: The TBPM and EBPM scores (9.05 +/- 3.59, 11.35 +/- 2.25
      respectively) of TBI patients were lower than that of controls (14.95 +/- 2.09,
      16.45 +/- 1.54, respectively) (P < 0.05). Compared with the controls, time
      monitoring frequency of the patients[times] was less (1 (1, 2) vs 4 (3, 5.25)
      times) (P < 0.05); cue discovery frequency also less (2 (2, 3) vs 5 (4.25, 5)
      times). And there were fewer note-taking subjects in TBI group (P < 0.05).
      CONCLUSION: With deficits in both the time- and event-based prospective memory,
      the TBI patients have difficulty of finding time or event cue during interference
      and auxiliary memory strategy is rarely utilized to realize the prospective
      memory tasks.

PMID- 24125670
TI  - [Ultrasonic scores of conventional ultrasound and ultrasound elastography in the
      diagnosis of thyroid nodular lesions].
AB  - OBJECTIVE: To explore the values of total ultrasonic scores of conventional
      ultrasound and ultrasound elastography in the diagnosis of thyroid nodular
      lesions. METHODS: A total of 347 thyroid nodules proved by fine-needle aspiration
      cytology (FNAC) and surgery underwent preoperative conventional ultrasound and
      ultrasound elastography. The features on gray scale, color Doppler flow imaging
      (CDFI) and elastograms were documented and total ultrasonic scores recorded.
      RESULTS: Among 347 nodules, 184 nodules were benign and 163 malignant.
      Significant differences of total ultrasonic scores were found between thyroid
      carcinoma and benign nodular lesions including the parameters of nodular shape,
      edge, echoes, sound attenuation, psammous calcifications, internal blood flow and
      ultrasound elastography score. The higher the total ultrasonic scores, the more
      possibility of thyroid carcinoma was. By the analysis of receiver operating
      characteristic curve, the sensitivity, specificity and accuracy of distinguishing
      thyroid carcinoma from benign nodular lesions was 84.0%, 89.6% and 84.9% if the
      cut-off value of total ultrasonic scores was over 4. CONCLUSION: For the
      differential diagnosis of benign and malignant thyroid lesions, the total
      ultrasonic scores of conventional ultrasound and ultrasound elastography can
      offer greater values.

PMID- 24125671
TI  - [Imaging findings of non-contrast CT scan, enhancement and HRCT of pulmonary
      mucosa-associated lymphoid tissue lymphoma].
AB  - OBJECTIVE: To explore the imaging findings of non-contrast CT scan, enhancement
      and HRCT of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS:
      All the patients with pathologically proven pulmonary MALT lymphoma underwent non
      contrast CT scan, of which 7 underwent CT enhancement and 9 had HRCT. CT features
      of 16 patients were retrospectively reviewed. RESULTS: Major CT signs of 16 cases
      were consolidations, nodules and masses, of which 11 had two or more signs and 5
      had only one. Together with them, normal or dilated air bronchograms were seen in
      13 cases, ground-glass opacity (GGO) in 10, interstitial changes and cysts in
      respective 5, partial atelectasis and mediastinal and hilar lymphoadenopathy in
      respective 4, pleural effusion in 2 and MALT lymphoma of tracheobronchial tree in
      1. Multiple lesions were found in 12 cases and solitary lesion in 4 cases.
      Consolidations, greater tubercles and masses mostly had a peribronchovascular
      distribution. Micronodules occurred in a perilymphatic distribution, of which 8
      accompanied other signs.On CT enhancement scans, greater tubercles in the trachea
      had mild enhancement; most of the consolidations and masses had obvious
      enhancement, while greater tubercles mostly mild enhancement. CT angiogram sign
      was found in 3 cases. CONCLUSION: Most cases with pulmonary MALT lymphoma have
      consolidations, greater tubercles and masses with normal or dilated air
      bronchograms which have a peribronchovascular distribution, together with GGO and
      micronodules in a perilymphatic distribution; the distinctive manifestations are
      obvious enhancement with CT angiogram sign. Minority cases have interstitial
      changes, cysts, partial atelectasis, mediastinal and hilar lymphoadenopathy,
      pleural effusion and MALT lymphoma of tracheobronchial tree.

PMID- 24125672
TI  - [Clinical application of multi-slice computed tomography angiography low-dose
      scan in pulmonary veins and left atrium].
AB  - OBJECTIVE: To investigate the clinical application of multi-slice computed
      tomography angiography (MSCTA) low-dose scan in pulmonary veins and left atrium
      and to reduce the radiation dose. METHOD: 100 middle-sized patients underwent
      pulmonary veins and left atrium MSCTA were collected and randomly divided into
      five groups averaged. The tube current were 250 mAs (conventional dose), 200,
      150, 100, and 80 mAs (low dose), respectively. The CT scan length (L), volume CT
      dose index (CTDIvol) and dose length product (DLP) of five groups were recorded
      automatically, and the effective dose(ED) was measured. The signal to noise ratio
      (SNR) and the contrast to noise (CNR) of thoracic aorta at the middle level of
      left atrium were measured to evaluate the image quality objectively. The image
      quality of pulmonary veins and left atrium MSCTA was evaluated by two experienced
      radiologists using double-blind method. The results were analyzed by statistics.
      RESULT: (1) The CTDIvol(mGy), DLP(mGy*cm) and ED decreased evidently with the
      scan dose reduced, and the difference had statistical significance. (2) The image
      quality was mainly excellent and good in 100 mAs and the above, and it was mainly
      good in 80 mAs group. The image quality decreased with mAs reduced. The
      difference of SNR and CNR within five groups had statistical significance. The
      satisfaction degree of subjective evaluation on image quality of the five groups
      was up to 100%. CONCLUSION: On the premise that the image quality confirmed to
      the clinical diagnosis, the low dose scan in pulmonary veins and left atrium SCTA
      can obviously reduce radiation dose, and it had important clinical significance.

PMID- 24125673
TI  - [Prognostic factors and outcomes of Legg-Calve-Perthes disease].
AB  - OBJECTIVE: To determine the prognostic factors and outcomes of Legg-Calve-Perthes
      (LCP) disease. METHODS: A retrospective review was conducted for a total of 144
      LCP patients at Department of Pediatric Orthopedics, Beijing Jishuitan Hospital.
      Their clinical data, such as age, gender, follow-up duration and radiological
      characteristics, were collected and assessed with Stulberg classification scheme.
      RESULTS: The male-to-female ratio was 8.6:1. Their age of onset was 8.06 +/- 2.01
      years and follow-up period 5.90 +/- 2.29 years. There were Stulberg I and II (n =
      52, 36.1%), III type (n = 57, 39.6%) and IV and V type (n = 35, 24.3%). Between
      the low-age ( <= 8) and high-age (>8) groups, the results of lateral pillar
      classification (A, B, C), modified Catterall staging (A, B) and Stulberg
      classification had significant differences (P < 0.005). Logistic regression
      analysis showed that age, lateral pillar classification and lateral half
      dislocation were independent prognostic risk factors. CONCLUSION: Age, lateral
      pillar classification and lateral half dislocation are prognostic factors for
      LCP. And greater age and higher lateral pillar classification denote a worse
      outcome.

PMID- 24125674
TI  - [Clinical efficacy of subtalar joint arthrodesis with percutaneous opposite
      parallel cannulated screws].
AB  - OBJECTIVE: To explore the clinical efficacy of subtalar joint arthrodesis with
      percutaneous opposite parallel cannulated screws for severe subtalar joint
      arthritis. METHODS: A total of 88 patients with 90 feet underwent subtalar joint
      fusion under four different incisions from April 2008 to April 2012. There were
      56 males and 32 females with a mean age of 43.7 (15-74) years. All of them were
      evaluated by radiography or computed tomography (CT) scan and assessed by the
      rating scores of visual analog scale (VAS) and American Orthopedic Foot and Ankle
      Society (AOFAS). RESULTS: Among them, 68 cases were followed up for an average of
      18.5 (6-48) months. Fusion was confirmed on radiography or CT in 67 cases with a
      fusion rate of 98.5%. The mean duration of fusion was 13.8 (6-28) weeks, the mean
      VAS score decreased from 6.00 to 1.03 points (P < 0.05) and the mean AOFAS score
      improved from 57.0 to 80.6 points (P < 0.05) with a good-and-excellent rate of
      80.8%. CONCLUSION: Subtalar joint arthrodesis with percutaneous opposite parallel
      cannulated screws is recommend for severe subtalar joint arthritis. Such a
      procedure has a high fusion rate, excellent clinical outcomes and fewer
      complications.

PMID- 24125675
TI  - [Comparison of blockage effect of axillary brachial plexus block between
      ultrasound guidance alone and ultrasound guidance plus neurostimulation].
AB  - OBJECTIVE: To compare the blockage effect of multiple injection axillary brachial
      plexus blockage between ultrasound guidance alone and ultrasound guidance plus
      neurostimulation. METHODS: Upon the approval of institutional ethical committee,
      a total of 166 patients underwent hand, forearm and distal arm operations under
      axillary brachial plexus blockage from January to May in 2011 at Department of
      Hand Surgery, Beijing Jishuitan Hospital. They were randomly allocated to receive
      either ultrasound guidance plus nerve stimulation (group US-NS, n = 83) or
      ultrasound guidance alone (group US, n = 83) for nerve localization. Ten
      milliliter ropivacaine 0.5% was administered separately on each nerve. Blockage
      time, needle frequency, success rate, onset of sensory and motor blocks,
      procedure-related complications (vascular puncture, acute nerve injury and
      tourniquet pain, etc.) and patient satisfaction were recorded. RESULTS: The
      procedure time was shorter in US group than in US-NS group [(3.3 +/- 1.5) vs (5.3
      +/- 2.0) min, P < 0.01]. The median (range) number of needle frequency of group
      US was lower than that of group US-NS [(4.3 +/- 0.7) vs (5.6 +/- 1.4) temps, P <
      0.01]. No intergroup difference existed in success rate. The onset of complete
      block was shorter in group US-NS than that in group US [(10.6 +/- 6.4) vs (12.7
      +/- 6.9) min, P < 0.05]. Vascular puncture proportion was higher in group US-NS
      than group US (16/83 vs 1/83, P < 0.01). There was no occurrence of tourniquet
      pain. Patient acceptance was similar in two groups. CONCLUSION: Multiple
      injection axillary blockage with ultrasound guidance yield similar success rates
      whether or not combined with nerve stimulation guidance. There appears to be a
      lower incidence rates of complications for ultrasound guidance alone versus
      ultrasound guidance plus neurostimulation.

PMID- 24125676
TI  - [Application of video endoscopic inguinal lymphadenectomy in radical vulvectomy
      for carcinoma].
AB  - OBJECTIVE: To evaluate the feasibility and safety of applying video endoscopic
      inguinal lymphadenectomy via hypogastric subcutaneous approach (VEIL-H) in the
      treatment of vulvar carcinoma. METHODS: From September 2009 to December 2012, 15
      patients with vulvar carcinoma underwent VEIL-H plus radical vulvectomy at many
      participating hospitals. RESULTS: All were treated surgically. Two of them
      underwent laparoscopic pelvic lymphadenectomy (LPL) upon the positive results of
      parotid operations with frozen section. The mean operative duration of VEIL-H
      (bilateral groin) were (80.8 +/- 2.9) minutes. The mean total volume of blood
      loss in VEIL was (5.5 +/- 0.4) ml, the mean drainage duration (6 +/- 2) days and
      the average postoperative hospitalization (11 +/- 4) days. The mean follow-up
      period was 13.0 months. One patient suffered local recurrence at Month 2
      postoperation. CONCLUSION: VEIL-H is both feasible and safe in inguinal
      lymphadenectomy.

PMID- 24125677
TI  - [Association of estrogen receptor beta gene polymorphisms with hypertension in
      postmenopausal women].
AB  - OBJECTIVE: To explore the association between estrogen receptor beta (ERbeta)
      gene polymorphisms and hypertension in postmenopausal women. METHODS: The
      relationship of two polymorphisms (rs944050 and rs4986938) with hypertension was
      examined in 71 postmenopausal women with hypertension and 50 healthy age-matched
      controls. RESULTS: In hypertension and control groups, the ERbeta allelic
      frequencies of A and G were 0.500, 0.500, 0.540, 0.460; 0.077, 0.923, 0.170,
      0.830 respectively. The genotypic distributions of both polymorphisms stayed
      within Hardy-Weinberg equilibrium. For polymorphism rs4986938, statistical
      difference existed between the wild-type genotype and a combination of
      heterozygous and homozygous variant genotypes (P < 0.05). The variant allele A of
      rs4986938 in ERbeta gene decreased the risk of hypertension (OR = 0.41, 95%CI
      0.18-0.92). CONCLUSION: The polymorphism rs4986938 in ERbeta gene was associated
      with an elevated risk of hypertension in Chinese Han postmenopausal women.

PMID- 24125678
TI  - [Surgical treatment of ruptured cerebellar arteriovenous malformations].
AB  - OBJECTIVE: To analyze the clinical characteristics and surgical outcomes of
      ruptured cerebellar arteriovenous malformations (AVM). METHODS: The clinical data
      were retrospectively analyzed for 676 brain AVM patients. Among them, 616 cases
      were treated at Beijing Tiantan Hospital from January 2003 to December 2009 and
      32 cases of them were of cerebellar AVM. Another 60 cases of intracranial AVM
      were managed at Beijing Chaoyang Hospital from January 2003 to December 2011 and
      there were 8 cases of cerebellar AVM. Microsurgery was performed to remove
      hematoma and excise AVM. And the postoperative outcomes were evaluated. RESULTS:
      Statistics analysis of activities of daily living (ADL) scores for 636 cases of
      cerebral AVM and 40 cases of cerebellar AVM showed no significant difference.
      Among 40 cases of cerebellar AVM, hemorrhage occurred first in 35 (87.5%)
      patients. Postoperative re-examinations of computed tomography revealed the
      resolution of hematoma and the absence of re-hemorrhage. Digital subtraction
      angiography (DSA) examinations were performed in 39 cases and no residual nidus
      was observed. Tonsillar herniation occurred preoperatively in 1 case and DSA was
      not re-examined. There were balance dysfunction (n = 3), dysarthria (n = 2) and
      dystaxia and dysphasia (n = 1). The postoperative ADL degrees were I(n = 26),
      II(n = 10), III(n = 3) and IV(n = 1). During a follow-up period of 6 months, no
      re-hemorrhage occurred and there was no worsening function of central nerve
      system. CONCLUSION: Emergency microsurgery is effective in the treatment of
      ruptured cerebellar AVM.

PMID- 24125679
TI  - [Che-1 participates in the regulation of rat cortical neuronal apoptosis and
      axonal regeneration after traumatic brain injury via p53].
AB  - OBJECTIVE: To explore the altered expressions of Che-1 in rat brain cortex and
      relative biological functions after traumatic brain injury. METHODS: According to
      a random number table, a total of 64 male Sprague-Dawley rats were divided into
      normal, sham and trauma group. Then the trauma group was further divided into 6
      phase sub-groups (12 h, 1 d, 3 d, 5 d, 7 d, 14 d) (n = 8 each). The
      craniocerebral injury (CCI) model was established to induce brain trauma at
      different time points. The examinations of Western blot and immunohistochemistry
      were performed to detect the expressions and diffusion changes of Che-1.
      Meanwhile the method of terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling (TUNEL) was employed to examine neuronal apoptosis.
      Additionally, the association of Che-1 with p53, active-caspase-3 and GAP43 was
      tested with Western blot and immunofluorescent staining. RESULTS: Compared with
      the normal and sham groups, the expression of Che-1 peaked at Day 3 post-injury
      (0.817 +/- 0.022, P < 0.05) and it was related with neuronal apoptosis. Moreover,
      the altered expressions of p53, GAP43 and active-caspase-3 were associated with
      the level of Che-1. CONCLUSION: The expression of Che-1 is elevated after brain
      trauma and may be involved in neuronal apoptosis and axonal regeneration through
      p53.

PMID- 24125680
TI  - [Combined application of neural stem cell and self-assembly isoleucine-lysine
      valine-alanine-valine nanofiber gel transplantation in the promotion of function
      recovery of spinal cord injury in rats].
AB  - OBJECTIVE: To observe the effects of neural stem cells (NSC) plus self-assembly
      isoleucine-lysine-valine-alanine-valine (IKVAV) nanofiber gel transplantation on
      the promotion of function recovery of spinal cord injury (SCI) in rats. METHODS:
      A total of 230 SD rats were randomized into gel, NSC, NSC plus self-assembly
      IKVAV nanofiber gel transplantation, normal saline and sham-operation groups.
      Function repair was evaluated by bundle branch block (BBB) score,
      immunofluorescence and Western blot respectively at Day 1, 3, 5, 7, 14, 28, 56
      and 92 post-operation. RESULTS: There were statistically significant differences
      among bundle branch block (BBB) scores of different treatment groups (P < 0.01).
      Moreover, statistical significance existed between each treatment group and
      combined transplantation group (P = 0.000). The expression of glial fibrillary
      acidic protein in combined transplantation group (rats with spinal injury) was
      lower than that in other treatment groups (except for sham operation) and the
      expression of NF-200 in this group was higher than that in other treatment groups
      (except for sham operation). Significant differences existed in the expressions
      of brain-derived neurotrophic factor and nerve growth factor between combined
      transplantation and other treatment groups (P < 0.01). CONCLUSION:
      Transplantation with IKVAV nanofiber gel, NSC and NSC plus self-assembly IKVAV
      nanofiber gel may promote the repair of SCI in rats. But the method of NSC plus
      self-assembly IKVAV nanofiber gel is more effective.

PMID- 24125681
TI  - [Effects on the secretion of reproductive hormones in adult female rats exposed
      to lipopolysaccharide in neonatal life].
AB  - OBJECTIVE: To explore whether neonatal endotoxin challenge alters reproductive
      hormone secretion in adult female rats. METHODS: Rats were intraperitoneally
      injected with lipopolysaccharide (LPS) or normal saline at postnatal days 3 and
      5. At Week 12, the animals underwent bilateral oophorectomy and were exposed to
      LPS or saline. The secretion levels of luteinizing hormone (LH) and estradiol
      were measured. RESULTS: The LPS injection in adult neonatal saline rats caused
      the suppressed secretion of LH and estradiol. However, the decreased secretion of
      both LH and estradiol were much more apparent in adult neonatal LPS-treated rats.
      CONCLUSION: The neonatal LPS challenge alters the secretions of LH and estradiol
      during adulthood. And the mechanism may be mediated by epigenetic programming of
      hypothalamic-pituitary-gonadal axis.

PMID- 24125682
TI  - [Relationship between chemokine axis CXCL12-CXCR4 and epithelial ovarian cancer].
AB  - OBJECTIVE: To explore the relationship between chemokine axis CXCL12-CXCR4 and
      the pathogenesis and severity of epithelial ovarian cancer. METHODS: SKOV3
      transfected with plasmid, SKOV3 transfected with vector and SKOV3 were cultured
      in vitro. Methyl thiazolyl tetrazolium (MTT) was used to analyze the effects of
      different concentrations of CXCL12 on the proliferation, migration and invasion
      of three cell lines and examine the inhibition of neutralizing CXCR4 antibody or
      antagonist AMD3100. And the load and weight of acquired tumor were determined at
      different concentrations of CXCL12. RESULTS: CXCL12 could promote the
      proliferation, migration and invasion of SKOV3/CXCR4 cells in a dose-dependent
      fashion (P < 0.05). The effect on CXCL12 tumorigenesis could be inhibited by
      neutralizing CXCR4 antibody or antagonist AMD3100 (P < 0.05). Significant
      differences existed in the mean survival time, load and weight of metastatic
      tumors among the three nude mice. CONCLUSION: A close correlation exists between
      chemokine axis CXCL12-CXCR4 and the pathogenesis, metastasis of epithelial
      ovarian cancer. The above axis may be an important pathogenic factor of
      epithelial ovarian cancer. And the antibody of CXCL12-CXCR4 is probably effective
      in its management.

PMID- 24125683
TI  - Ion channel stability of Gramicidin A in lipid bilayers: effect of hydrophobic
      mismatch.
AB  - Hydrophobic mismatch which is defined as the difference between the lipid
      hydrophobic thickness and the peptide hydrophobic length is known to be
      responsible in altering the lipid/protein dynamics. Gramicidin A (gA), a 15
      residue beta helical peptide which is well recognized to form ion conducting
      channels in lipid bilayer, may change its structure and function in a hydrophobic
      mismatched condition. We have performed molecular dynamics simulations of gA
      dimer in phospholipid bilayers to investigate whether or not the conversion from
      channel to non-channel form of gA dimer would occur under extreme negative
      hydrophobic mismatch. By varying the length of lipid bilayers from DLPC (1, 2
      Dilauroyl-sn-glycero-3-phosphocholine) to DAPC (1, 2-Diarachidoyl-sn-glycero-3
      phosphocholine), a broad range of mismatch was considered from nearly matching to
      extremely negative. Our simulations revealed that though the ion-channel
      conformation is retained by gA under a lesser mismatched situation, in extremely
      negative mismatched situation, in addition to bilayer thinning, the conformation
      of gA is changed and converted to a non-channel one. Our results demonstrate that
      although the channel conformation of Gramicidin A is the most stable structure,
      it is possible for gA to change its conformation from channel to non-channel
      depending upon the local environment of host bilayers. 

PMID- 24125684
TI  - In vitro model systems for studying the impact of organic chemicals on the skin
      barrier lipids.
AB  - This paper describes two synthetic lipid models designed to replace human stratum
      corneum (SC) in studies of the impact of volatile organic chemicals on the
      molecular organization of the skin barrier lipids. The models built upon
      previously developed self-assembled lipid membranes which have composition and 3D
      organization similar to those of the lipid matrix in SC. In one model the target
      chemicals were incorporated in the lipids before their self-assembly, and in the
      other one they were applied on top of a preformed lipid membrane. The chemicals
      could be incorporated within the model membranes in quantities close to those
      reached within human SC upon heavy surface loading. The dose-dependent effects of
      the chemicals on the lateral molecular organization in the models were
      qualitatively identical to those observed by infrared spectroscopy in human SC.
      The models facilitated the interpretation of X-ray diffraction profiles used to
      determine the nature of the interactions between the chemicals and the lipid
      lamellae and the position of the exogenous molecules within the unit cell of the
      lipid phases. These model systems are suitable for in vitro studies in the areas
      of skin biophysics, dermatology, transdermal drug delivery, and risk assessment. 

PMID- 24125685
TI  - The benefits of rule following: A new account of the evolution of desires.
AB  - A key component of much current research in behavioral ecology, cognitive
      science, and economics is a model of the mind at least partly based on beliefs
      and desires. However, despite this prevalence, there are still many open
      questions concerning both the structure and the applicability of this model. This
      is especially so when it comes to its 'desire' part: in particular, it is not yet
      entirely clear when and why we should expect organisms to be desire-based
      understood so as to imply that they consult explicit tokenings of what they ought
      to do-as opposed to being drive-based-understood so as to imply that they react
      to the world using behavioral reflexes. In this paper, I present the beginnings
      of an answer to this question. To do this, I start by showing that an influential
      recent attempt to address these issues-due to Kim Sterelny-fails to be fully
      successful, as it does not make sufficiently clear what the relative benefits and
      disadvantages of drive-based and desire-based cognitive architectures are. I then
      present an alternative account of this matter based on the idea that organisms
      that can follow explicit behavioral rules (i.e. which have desires) avoid having
      to memorize a large set of state of the world-action connections-which can
      (though need not) be adaptive. Finally, I apply this account to the question of
      what the cognitive value of mental representations should be seen to be; here, I
      conclude that-contrary to some recent claims-relying on mental representations
      can make decision making easier, not harder, but also that-in line with these
      recent claims-whether it does so depends on the details of the case. 

PMID- 24125686
TI  - Exploring the biologically relevant chemical space for drug discovery.
AB  - Both recent studies and our calculation suggest that the physicochemical
      properties of launched drugs changed continuously over the past decades. Besides
      shifting of commonly used properties, the average biological relevance (BR) and
      similarity to natural products (NPs) of launched drugs decreased, reflecting the
      fact that current drug discovery deviated away from NPs. To change the current
      situation characterized by high investment but low productivity in drug
      discovery, efforts should be made to improve the BR of the screening library and
      hunt drugs more effectively in the biologically relevant chemical space.
      Additionally, a multiple dimensional molecular descriptor, named the biologically
      relevant spectrum (BRS) was proposed for quantitative structure-activity
      relationships (QSAR) study or screening library preparation. Prediction models
      for 43 biological activity categories were developed with BRS and support vector
      machine (SVM). In most cases, the overall prediction accuracies were around 95%
      and the Matthew's correlation coefficients (MCC) were over 0.8. Thirty-seven out
      of 48 drug-activity associations were successfully predicted for drugs that
      launched from 2006 to 2012, which were not included in the training data set. A
      web-server named BioRel ( http://ibi.hzau.edu.cn/biorel ) was developed to
      provide services including BR, BRS calculation, activity class, and
      pharmacokinetic property prediction. 

PMID- 24125687
TI  - Correlating Novice Nurses' Perceptions of Nursing Orientation and First-Year
      Support With Direct Preceptor Interventions.

PMID- 24125688
TI  - Safety of the "drain and retain" option for defunctionalized urologic prosthetic
      balloons and reservoirs during artificial urinary sphincter and inflatable penile
      prosthesis revision surgery: 5-year experience.
AB  - OBJECTIVE: To present our 5-year experience using a "drain and retain" option, in
      which existing urologic prosthetic balloons and reservoirs (UPBR) were emptied
      but not removed during routine artificial urinary sphincter (AUS)/inflatable
      penile prosthesis (IPP) reoperation. METHODS: All genitourinary prosthetic
      surgeries by a single surgeon from July 2007 to September 2012 were reviewed.
      Patients were included in the study group if they underwent prosthetic
      replacement (with contralateral new UPBR placement) or subtotal device removal,
      although having their original UPBR drained and retained. Virgin cases, complete
      device removals for gross infection, and revision cases using the original UPBR
      were excluded. The "drain and retain" technique involved defunctionalizing the
      existing UPBR by aspirating all its fluid, placing the tubing on traction, and
      cutting proximally. Postoperative outcomes with specific attention to infection
      were reviewed and compared with patients receiving their first prosthesis
      (control group). RESULTS: A total of 551 urologic prostheses (251 AUS and 300
      IPP) were inserted in 433 men during the 5-year study period. Among 120
      reoperative prosthetic cases, UPBR were drained and retained in 55 (46%). The
      control group consisted of 352 patients undergoing initial AUS (154 cases) and/or
      IPP (236 cases) placement. No difference in infection rate was identified between
      the control group (6 of 390; 1.5%) and the "drain and retain" group (1 of 55;
      1.8%; chi-square = 0.024; P = .88). CONCLUSION: Retention of defunctionalized
      uninfected genitourinary prosthetic balloons and reservoirs does not increase
      complication rate during reoperative AUS and/or IPP surgery.

PMID- 24125689
TI  - Understanding avoidance, refusal, and abandonment of chemotherapy before and
      after cystectomy for bladder cancer.
AB  - OBJECTIVE: To analyze trends in perioperative chemotherapy and optimize use of
      neoadjuvant chemotherapy for bladder cancer. METHODS: From 2005-2012, 284
      consecutive patients underwent robot-assisted radical cystectomy at our facility.
      Patients with disease >= T2 and nodal involvement and positive surgical margins
      were reviewed and considered candidates for referral to medical oncology for
      chemotherapy. The study was conducted in two phases: phase 1 included 242
      consecutive patients between 2005 and 2011, and phase 2 analyzed the effect of
      changes in 42 patients during a 1-year period (2011-2012). RESULTS: In phase 1,
      148 patients (61%) were candidates for neoadjuvant chemotherapy (NAC).
      Consultation for NAC was sought for 44 patients (29%), and 104 (71%) did not
      receive consultation. Of the 44 patients, 36% received NAC, 7% refused, 32% were
      recommended for immediate cystectomy, and 25% did not receive NAC for other
      reasons. Phase 2 was more stringent, with a multidisciplinary approach.
      Significant improvement in referral and NAC use was seen. About 78% vs 30% of
      patients were seen by medical oncology for consideration of NAC before robot
      assisted radical cystectomy and 71% vs 36% received NAC compared with phase 1.
      The NAC utilization rate improved from 10.8% to 55% over 1 year with a diligent
      multidisciplinary approach. Medical comorbidities were the main reason for
      patients not receiving adjuvant chemotherapy (AC; 30% and 33%). CONCLUSION: A
      multidisciplinary approach and coordination of services can help optimize the use
      of neoadjuvant chemotherapy for bladder cancer.

PMID- 24125690
TI  - Editorial comment.

PMID- 24125691
TI  - Defer or treat? Reasons for treatment decisions in patients with chronic
      hepatitis C genotype 1 in the early era of directly acting antiviral agents.
AB  - BACKGROUND: In chronic genotype 1 hepatitis C, telaprevir or boceprevir plus
      peginterferon and ribavirin have become the new standard of care. Aim of this
      study was to identify factors contributing to the decision whether to defer or
      treat with the current triple regimens. METHODS: Prospective assessment of eight
      parameters on 0-4-point scales by the attending physician at a German tertiary
      referral centre between 1st September 2011 and 31st December 2012. RESULTS: 307
      patients were evaluated at least once by one of the 11 hepatologists involved;
      267 patients were considered, but only 163 were recommended to receive triple
      therapy. Multivariate regression analysis revealed that a higher degree of
      fibrosis was most strongly associated with a recommendation for treatment (OR
      2.69), followed by the patients' demand (OR 2.27), presumed efficacy (OR 1.62),
      and tolerability (OR 1.58). A high risk of decompensation was associated with the
      decision to defer (OR 0.39). Speed of progression, compliance, extrahepatic
      manifestation, gender and age were not significantly related to the
      recommendation. Treatment was finally started in 101 patients (32.9%).
      CONCLUSION: In chronic genotype 1 hepatitis C, advanced fibrosis and patients'
      preference are the main rationales to choose treatment rather than deferral in a
      real-life setting.

PMID- 24125692
TI  - A fatigue loading model for investigation of iatrogenic subtrochanteric fractures
      of the femur.
AB  - BACKGROUND: Biomechanics of iatrogenic subtrochanteric femur fractures have been
      examined. Previously-described loading models employed monotonic loading on the
      femoral head, which is limited in emulating physiological features. We
      hypothesize that cyclic loading combined with the engagement of abductor forces
      will reliably cause iatrogenic subtrochanteric fractures. METHODS: Finite element
      analysis determined the effects of adding the abductor muscle forces to the hip
      contact force around holes located in the lateral femoral cortex. Finite element
      analysis predictions were validated by strain gage measurements using SawbonesTM
      femurs (Pacific Research Laboratories, Inc., Vashon, Washington, USA) with or
      without abductor muscle forces. The newly developed physiologically-relevant
      loading model was tested on cadaveric femurs (N=8) under cyclic loading until
      failure. FINDINGS: Finite element analysis showed the addition of the abductor
      muscle forces increased the maximum surface cortical strain by 107% and the
      strain energy density by 332% at the lateral femoral cortex. Strain gages
      detected a 72.9% increase in lateral cortical strain using the combined loading
      model. The cyclic, combined loading led to subtrochanteric fractures through the
      drill hole in all cadaveric femurs. INTERPRETATION: Finite element analysis
      simulations, strain gage measurements, and cyclic loading of fresh-frozen femurs
      indicate the inclusion of abductor forces increases the stress and strain at the
      proximal-lateral femoral cortex. Furthermore, a cyclic loading model that
      incorporates a hip contact force and abductor muscles force creates the
      clinically encountered subtrochanteric fractures in vitro. This physiologically
      relevant loading model may be used to further study iatrogenic subtrochanteric
      femur fractures.

PMID- 24125693
TI  - The heat-inducible essential response regulator WalR positively regulates
      transcription of sigI, mreBH and lytE in Bacillus subtilis under heat stress.
AB  - The actin homolog MreBH governs cell morphogenesis of Bacillus subtilis through
      localization of the cell wall hydrolase LytE. The alternative sigma factor SigI
      of B. subtilis coordinately regulates transcription of mreBH and lytE.
      Transcription of sigI, mreBH and lytE is heat-inducible. The essential response
      regulator WalR (YycF) plays a key role in coordinating cell wall metabolism with
      cell proliferation. We now demonstrate that mreBH is a new member of the WalR
      regulon. We also found that WalR can positively and directly regulate sigI
      transcription under heat stress through a binding site located upstream of the
      sigma(I) promoter of sigI. In addition, we found that a WalR binding site located
      upstream of the SigI binding site in the regulatory region of lytE is important
      for lytE expression under heat stress. Moreover, we found that walR is a new
      member of the heat shock stimulon of B. subtilis. WalR appears to coordinately
      and positively regulate transcription of sigI, mreBH and lytE under heat stress.
      Finally, our work shows for the first time that WalR can stimulate activities of
      sigma(I) promoters under heat stress.

PMID- 24125694
TI  - Motility of Pseudomonas aeruginosa contributes to SOS-inducible biofilm
      formation.
AB  - DNA-damaging antibiotics such as ciprofloxacin induce biofilm formation and the
      SOS response through autocleavage of SOS-repressor LexA in Pseudomonas
      aeruginosa. However, the biofilm-SOS connection remains poorly understood. It was
      investigated with 96-well and lipid biofilm assays. The effects of ciprofloxacin
      were examined on biofilm stimulation of the SOS mutant and wild-type strains. The
      stimulation observed in the wild-type in which SOS was induced was reduced in the
      mutant in which LexA was made non-cleavable (LexAN) and thus SOS non-inducible.
      Therefore, the stimulation appeared to involve SOS. The possible mechanisms of
      inducible biofilm formation were explored by subproteomic analysis of outer
      membrane fractions extracted from biofilms. The data predicted an inhibitory role
      of LexA in flagellum function. This premise was tested first by functional and
      morphological analyses of flagellum-based motility. The flagellum swimming
      motility decreased in the LexAN strain treated with ciprofloxacin. Second, the
      motility-biofilm assay was performed, which tested cell migration and biofilm
      formation. The results showed that wild-type biofilm increased significantly over
      the LexAN. These results suggest that LexA repression of motility, which is the
      initial event in biofilm development, contributes to repression of SOS-inducible
      biofilm formation. 

PMID- 24125695
TI  - Characterization of pbt genes conferring increased Pb2+ and Cd2+ tolerance upon
      Achromobacter xylosoxidans A8.
AB  - The cluster of pbtTFYRABC genes is carried by plasmid pA81. Its elimination from
      Achromobacter xylosoxidans A8 resulted in increased sensitivity towards Pb(2+)
      and Cd(2+). Predicted pbtTRABC products share strong similarities with Pb(2+)
      uptake transporter PbrT, transcriptional regulator PbrR, metal efflux P1-ATPases
      PbrA and CadA, undecaprenyl pyrophosphatase PbrB and its signal peptidase PbrC
      from Cupriavidus metallidurans CH34. Expression of pbtABC or pbtA in a metal
      sensitive Escherichia coli GG48 rendered the strain Pb(2+)-, Cd(2+)- and Zn(2+)
      tolerant and caused decreased accumulation of the metal ions. Accumulation of
      Pb(2+), but not of Cd(2+) or Zn(2+), was promoted in E. coli expressing pbtT.
      Additional genes of the pbt cluster are pbtF and pbtY, which encode the cation
      diffusion facilitator (CDF)-like transporter and a putative fatty acid
      hydroxylase of unknown function, respectively. Expression of pbtF did not confer
      increased metal tolerance upon E. coli GG48, although the protein showed
      measurable Pb(2+)-efflux activity. Unlike the pbtT promoter, promoters of pbtABC,
      pbtF and pbtY contain features characteristic of promoters controlled by metal
      responsive transcriptional regulators of the MerR family. Upregulation of pbtABC,
      pbtF and pbtY upon Pb(2+), Cd(2+) and Zn(2+) exposure was confirmed in wild-type
      Achromobacter xylosoxidans A8. Gel shift assays proved binding of purified PbtR
      to the respective promoters.

PMID- 24125696
TI  - Use of a multi-criteria analysis framework to inform the design of risk based
      general surveillance systems for animal disease in Australia.
AB  - Australia is a major exporter of livestock and livestock products; a trade
      assisted by a favourable animal health status. However, increasing international
      travel and trade, land use changes and climatic change increase the risks of
      exotic and emerging diseases. At the same time, public sector resources for
      managing these risks are static or declining. Animal health authorities in
      Australia identified the need to develop a consistent national approach to
      surveillance that allocates resources according to risk. A study was undertaken
      to assess the relative likelihood of occurrence of eight significant diseases of
      concern to animal health authorities with the aim of producing risk maps to
      better manage animal disease surveillance. The likelihood of disease occurrence
      was considered in terms of the likelihood that a disease is introduced and the
      likelihood that the disease establishes and spreads. Pathways for introduction
      and exposure and for establishment and spread were identified and data layers
      representing the factors contributing to each pathway produced as raster maps. A
      multi-criteria analysis process was used to combine data layers into pathways and
      pathways into likelihood maps using weightings that reflect the relative
      importance of each layer and pathway. The likelihood maps for introduction and
      exposure and for establishment and spread were combined to generate national
      likelihood maps for each disease. To inform Australia's general surveillance
      system that exists to detect any disease of importance, the spatial profiles of
      the eight diseases were subsequently combined using weightings to reflect their
      relative consequences. The result was a map of relative likelihood of occurrence
      of any significant disease. Current surveillance activity was assessed by
      combining data layers for government disease investigations, proximity to vets
      and wildlife disease investigations. Comparison of the overall risk and current
      surveillance maps showed that the distribution of current effort was well matched
      to the distribution of risk. 

PMID- 24125698
TI  - Substituent effects on the catalytic activity of bipyrrolidine-based iron
      complexes.
AB  - The catalytic activity and the selectivity of the new bipyrrolidine-based Fe(II)
      complexes 2.Fe(OTf)2 and 3.Fe(OTf)2 in the oxidation of a series of alkyl and
      alkenyl hydrocarbons as well as of an aromatic sulfide with H2O2 were tested and
      compared with the catalytic efficiency of White's parent complex 1.Fe(OTf)2 in
      order to evaluate the sensitivity of the reaction to electronic effects. 

PMID- 24125697
TI  - Days-lost to training and competition in relation to workload in 263 elite show
      jumping horses in four European countries.
AB  - Orthopaedic, or other, injuries in sports medicine can be quantified using the
      'days-lost to training' concept. Both the training regimen and the surface used
      in training and racing can affect the health of racehorses. Our aim was to
      associate 'days-lost to training' in elite-level show-jumpers to horse
      characteristics, training and management strategies, and the time spent working
      on various training and competition surfaces. We designed a longitudinal study of
      professional riders in four European countries. Data were recorded using training
      diaries. Reasons for days-lost were classified into non-acute and acute
      orthopaedic, medical, hoof-related, and undefined. We produced descriptive
      statistics of training durations, relative to type of training, surfaces used,
      and days-lost. We created zero-inflated negative-binomial random-effects models
      using the overall days-lost as outcome. In the whole dataset, duration variables
      related to training surfaces were analysed as independent. The Swedish data only
      were also used to test whether duration variables were related to competition
      surfaces. Thirty-one riders with 263 horses provided data on 39,028 days at risk.
      Of these, 2357 (6.0%) were days-lost (55% and 22% of these were due to non-acute
      and acute orthopaedic injuries, respectively) in 126 horses. In the all-country
      model, controlling for season, a significant variable was country. Switzerland
      and the UK had lower incidence-rate ratios (IR) compared to Sweden (IRs 0.2 and
      0.03, respectively). Horses with previous orthopaedic problems had almost a
      doubled IR (1.8) of days-lost due to orthopaedic injury, compared to baseline. If
      the horse had jumping training more than 1 min per day at risk the IRs were 6.9-7
      (compared to less than this amount of time); this was, however, likely an effect
      of a small baseline. Variation in training was a protective factor with a dose
      response relationship; the category with the highest variation had an IR of 0.1.
      In the Swedish model, controlling for season, there was an association of year
      (IR 2.8 year 2010). Further, if the horse rested >17-25% of the days at risk, or
      >33% of the DAR2, had IRs 3.5 and 3.0, compared to less time. Horses >= 6 years
      had IRs of 1.8-2.0, compared to younger horses. Limited training use of sand
      surface was a risk-factor (IR 2.2; >4 <= 12 min/day at risk), compared to not
      training on sand. Training/competing on sand-wood was a protective factor (IRs
      0.4-0.5) compared to not using this surface.

PMID- 24125699
TI  - The mitochondrial F1FO-ATPase desensitization to oligomycin by tributyltin is due
      to thiol oxidation.
AB  - The antibiotic oligomycin is known to inhibit mitochondrial F-type ATP synthases.
      The antibiotic inhibits both ATP synthesis and hydrolysis by blocking the H(+)
      translocation through FO which is coupled to the catalytic activity of F1. The
      amphiphilic organotin tri-n-butyltin (TBT), a known mitochondrial poison, can
      penetrate into biological membranes and covalently bind to electron-donor atoms
      of biomolecules such as sulfur. This study aims at exploring the mechanism(s)
      involved in the enzyme desensitization to oligomycin which occurs at
      concentrations >1 MUM TBT. This poorly known effect of TBT, which only appeared
      at temperatures above the break in the Arrhenius plot of the enzyme activity, was
      found to be accompanied by the oxidation of isolated thiol groups of the
      mitochondrial complex. The oligomycin sensitivity was restored by the reducing
      agents glutathione and dithioerythritol and not influenced by antioxidants. The
      whole of data is consistent with the hypothesis that thiol oxidation is caused by
      TBT covalent binding to cysteine residues in a low-affinity site on FO and not by
      other possible oxidative events. According to this putative model, the onset of
      tin-sulfur bonds would trigger conformational changes and weaken the oligomycin
      interaction with FO.

PMID- 24125700
TI  - Self-management of patient body position, pose, and motion using wide-field, real
      time optical measurement feedback: results of a volunteer study.
AB  - PURPOSE: We present the results of a clinical feasibility study, performed in 10
      healthy volunteers undergoing a simulated treatment over 3 sessions, to
      investigate the use of a wide-field visual feedback technique intended to help
      patients control their pose while reducing motion during radiation therapy
      treatment. METHODS AND MATERIALS: An optical surface sensor is used to capture
      wide-area measurements of a subject's body surface with visualizations of these
      data displayed back to them in real time. In this study we hypothesize that this
      active feedback mechanism will enable patients to control their motion and help
      them maintain their setup pose and position. A capability hierarchy of 3
      different level-of-detail abstractions of the measured surface data is
      systematically compared. RESULTS: Use of the device enabled volunteers to
      increase their conformance to a reference surface, as measured by decreased
      variability across their body surfaces. The use of visual feedback also enabled
      volunteers to reduce their respiratory motion amplitude to 1.7 +/- 0.6 mm
      compared with 2.7 +/- 1.4 mm without visual feedback. CONCLUSIONS: The use of
      live feedback of their optically measured body surfaces enabled a set of
      volunteers to better manage their pose and motion when compared with free
      breathing. The method is suitable to be taken forward to patient studies.

PMID- 24125701
TI  - Electrochemical serotonin monitoring of poly(ethylenedioxythiophene):poly(sodium
      4-styrenesulfonate)-modified fluorine-doped tin oxide by predeposition of self
      assembled 4-pyridylporphyrin.
AB  - A 5,10,15,20-tetrakis(4-pyridyl)-21H,23H-porphyrin (TPyP)-modified self-assembled
      functional layer was prepared on a fluorine-doped tin oxide (FTO) substrate. We
      employed a bifunctional molecule, 3-iodopropionate (3IP), to covalently bind TPyP
      to the FTO substrate. The 3IP-monolayered FTO and the TPyP-3IP-bilayered FTO
      electrodes were characterized by cyclic voltammetry, electrochemical impedance
      spectroscopy, and Fourier transform-infrared spectroscopy. Compared to
      conventional electropolymerized poly(ethylenedioxythiophene):poly(sodium 4
      styrenesulfonate) (PEDOT:PSS) film on bare FTO, the PEDOT:PSS film on the TPyP
      3IP-bilayered FTO showed better sensitivity and selectivity in monitoring
      serotonin in the presence of high concentrations of interfering agents such as
      ascorbic acid, urea, D-(+)-glucose, epinephrine, and L-3,4
      dihydroxyphenylalanine. Both PEDOT:PSS films on the bare FTO and the TPyP-3IP
      bilayered FTO showed electrocatalytic effects in serotonin detection, and only
      the TPyP-3IP-based PEDOT:PSS film acted as a pH resistant buffer layer in the
      selective detection of serotonin.

PMID- 24125702
TI  - Editorial comment.

PMID- 24125703
TI  - Retinal visual processing constrains human ocular following response.
AB  - Ocular following responses (OFRs) are the initial tracking eye movements elicited
      at ultra-short latency by sudden motion of a textured pattern. We wished to
      evaluate quantitatively the impact that subcortical stages of visual processing
      might have on the OFRs. In three experiments we recorded the OFRs of human
      subjects to brief horizontal motion of 1D vertical sine-wave gratings restricted
      to an elongated horizontal aperture. Gratings were composed of a variable number
      of abutting horizontal strips where alternate strips were in counterphase. In one
      of the experiments we also utilized gratings occupying a variable number of
      horizontal strips separated vertically by mean-luminance gaps. We modeled retinal
      center/surround receptive fields as a difference of two 2-D Gaussian functions.
      When the characteristics of such local filters were selected in accord with the
      known properties of primate retinal ganglion cells, a single-layer model was
      capable to quantitatively account for the observed changes in the OFR amplitude
      for stimuli composed of counterphase strips of different heights (Experiment 1),
      for a wide range of stimulus contrasts (Experiment 2) and spatial frequencies
      (Experiment 3). A similar model using oriented filters that resemble cortical
      simple cells was also able to account for these data. Since similar filters can
      be constructed from the linear summation of retinal filters, and these filters
      alone can explain the data, we conclude that retinal processing determines the
      response to these stimuli. Thus, with appropriately chosen stimuli, OFRs can be
      used to study visual spatial integration processes as early as in the retina. 

PMID- 24125704
TI  - Development of acquired idiopathic generalized anhidrosis in a case of Vogt
      Koyanagi-Harada disease.

PMID- 24125705
TI  - Simultaneous removal of SO2 and NO2 using a Mg-Al oxide slurry treatment.
AB  - SO2 and NO2 were simultaneously removed from a mixed gas using a Mg-Al oxide
      slurry treatment. Both adsorption to the oxide material itself and dissolution of
      the gases in the aqueous slurry contributed to the removal. A comparison was made
      between removal of the two gases separately and the simultaneous process. The
      removal of SO2 using both the simultaneous and individual process was similar;
      however, the removal of NO2 was lower for the simultaneous process. For the
      individual treatments, SO2 and NO2 were separately dissolved in the Mg-Al oxide
      slurry to produce SO3(2-), NO2(-), and NO3(-), which were subsequently removed by
      the Mg-Al oxide. However, when the simultaneous process was employed, the
      dissolved gases were seen to have a significant effect on each other. It was
      speculated that the production of NO2(-) was increased by the reduction of NO2 by
      SO3(2-). On increasing the quantity of the Mg-Al oxide, or on raising the
      temperature of the system, the removal of SO2 increased, with a concurrent
      decrease in NO2 removal. The increase in removal of SO3(2-) was speculated to
      hinder the conversion of NO2 to NO2(-), therefore decreasing the removal of the
      nitrogen species. The results demonstrate that the Mg-Al oxide slurry was highly
      effective for simultaneously removing NO2 and SO2 from a mixed gas. 

PMID- 24125706
TI  - Occurrence, seasonal variation and inhalation exposure of atmospheric
      organophosphate and pyrethroid pesticides in an urban community in South China.
AB  - The shift in pesticide usage patterns demands a better understanding of the
      occurrence, fate and exposure risk of atmospheric current-use pesticides (CUPs).
      Air samples collected in different seasons from an urban community in Guangzhou,
      China were analyzed to investigate seasonal variation, gas-particle partitioning
      and inhalation exposure of atmospheric organophosphate and pyrethroid pesticides.
      Chlorpyrifos and eight pyrethroids were detected in the air samples and the total
      concentrations of the nine CUPs ranged from 150 to 3816 pg m(-3). Chlorpyrifos
      and cypermethrin were the most dominant CUPs detected in the atmosphere,
      accounting for 68% and 15% of the total CUPs, respectively. Seasonal variation in
      concentration was observed for most CUPs, with peak concentrations occurring in
      summer and fall, which was consistent with their application patterns.
      Partitioning of chlorpyrifos between gas and particle phases was also seasonally
      dependent, with more chlorpyrifos found in the gas phase in summer and fall.
      Additionally, gas-particle partitioning analysis suggested that chlorpyrifos
      might experience long-range transport. Evaluation of potential exposure from
      inhalation of atmospheric CUPs suggested that children, toddlers and infants had
      the highest exposure, but the risk quotients were low for all age groups when
      annual average concentrations were used as exposure metrics. Exposure risk was
      higher in summer and fall than the annual average level due to higher atmospheric
      pesticide concentrations, longer exposure times and more pesticides being in the
      gaseous form.

PMID- 24125707
TI  - PFHxS induces apoptosis of neuronal cells via ERK1/2-mediated pathway.
AB  - Perfluorohexanesulfonate (PFHxS) is one of the most widely distributed
      perfluoroalkyl compounds (PFCs) and its possible neurotoxicity has been
      suggested. However, the effects of PFHxS on neuronal function remain to be
      elucidated. In this study, the effects of PFHxS on neuronal cell death and the
      underlying mechanisms were examined. Cerebellar granule cells (CGCs) were
      isolated from 7-day old rat pups and maintained in culture for additional 7d. The
      apoptotic effects of PFHxS were determined by caspase-3 activity and TUNEL
      staining. PFHxS increased the apoptotic death of CGC in concentration-dependent
      manner. It also increased the activation of ERK1/2, JNK and p38 MAPK with
      different temporal activation. PD98059, an inhibitor of ERK1/2 pathway,
      completely blocked PFHxS-induced apoptosis whereas SP600125, a JNK inhibitor,
      significantly increased the apoptosis, showing their opposite roles in the
      apoptosis of CGCs. Treatment of antioxidants, Trolox or N-acetylcysteine (NAC),
      completely blocked ROS generation by PFHxS but neither of these antioxidants
      prevented PFHxS-induced apoptosis, suggesting that ROS may not play a key role in
      the process of apoptosis. PD98059 prevented ROS accumulation by PFHxS but the
      ERK1/2 activation was not affected by Trolox or NAC. These results indicate that
      ROS is one of downstream targets of ERK1/2, not vice versa. Taken together, PFHxS
      increased apoptosis of CGC in ERK1/2-dependent manner, where downstream pathway
      other than ROS may play a major role. This is a first report that PFHxS induces
      apoptosis of CGC isolated from the developing brain and its possible mode of
      action is associated with ERK1/2 pathway. 

PMID- 24125708
TI  - Endosulfan induced cell death in Sertoli-germ cells of male Wistar rat follows
      intrinsic mode of cell death.
AB  - Health of germ cells may affect production of quality gametes either due to
      endogenous or exogenous factors. Pesticides are among the exogenous factors that
      can enter the organisms through various routes of exposure and also can affect
      the reproductive system of an organism. Endosulfan is an organochlorine
      cyclodiene pesticide used widely for controlling agricultural pests. It has been
      shown to induce reproductive dysfunctions such as sperm abnormalities, reduced
      intracellular spermatid count in exposed organisms. Germ cells being the
      progenitor cells for male gametes and Sertoli cells as their nourishing cells, we
      examined whether endosulfan induces cell death in Sertoli-germ cells of male
      rats. Sertoli-germ cells, isolated from 28 d old male Wistar rats, were exposed
      to endosulfan (2.0, 20.0 and 40.0 MUg mL(-1)) for 24-72 h. Cytotoxicity,
      endosulfan concentration, reactive oxygen species (ROS) generation, oxidative
      stress parameters were measured in these cells in the absence or presence of
      endosulfan for the above mentioned exposure periods and subsequently, cell death
      endpoints were measured. We detected endosulfan in the exposed cells and
      demonstrated increased cell death in exposed Sertoli-germ cells as evidenced by a
      significant increase in annexin-V staining, depolarization of mitochondrial
      membrane, caspase-9 and -3 activities and BAD and PARP cleavage activities and
      DNA ladder formation along with non-significant increase in autophagic cell
      death. The study suggests that endosulfan can cause cell death in exposed Sertoli
      germ cells due to higher oxidative damage with the activation of intrinsic cell
      death pathway which may eventually affect the production of quality gametes.

PMID- 24125709
TI  - C60 reduces the bioavailability of mercury in aqueous solutions.
AB  - The effects of C60 on mercury bioavailability and sorption were investigated at
      different C60 dosages, reaction times, and pH ranges using the merR::luxCDABE
      bioluminescent bioreporter Escherichia coli ARL1. The results demonstrated that
      the bioavailability of mercury (Hg(2+)) decreased with increasing C60 dosage.
      Approximately 30% of aqueous mercury became biologically unavailable 2h after
      interaction with C60 at a mass ratio of C60 to mercury as low as 0.01. However,
      this reduction in bioavailability plateaued at a mass ratio of C60 to mercury of
      10 with a further increase in C60 concentrations resulting in only a 20%
      additional decrease in bioavailability. If this reduction in bioluminescence
      output is attributable to mercury sorption on C60, then each one log-order
      increase in C60 concentration resulted in a 0.86 log-order decrease in the
      mercury partitioning coefficient (Kd). This relationship implies the presence of
      high mercury-affinitive sites on C60. The length of reaction time was found to
      play a more important role than C60 dosage in reducing Hg(2+) bioavailability,
      suggesting an overall slow kinetics of the C60-Hg interactions. In addition,
      lowering the pH from 7.2 to 5.8 decreased mercury bioavailability due likely to
      the increase in mercury's association with C60. These results suggest that C60
      may be useful in capturing soluble mercury and thus reducing mercury biotoxicity.

PMID- 24125710
TI  - Application of excitation and emission matrix fluorescence (EEM) and UV-vis
      absorption to monitor the characteristics of Alizarin Red S (ARS) during electro
      Fenton degradation process.
AB  - Oxidative degradation of Alizarin Red S (ARS) in aqueous solutions by using
      electro-Fenton was studied. At first, effect of operating parameters such as
      current density, aeration rate and initial pH on the degradation of ARS were
      studied by using UV-vis spectrum, respectively. Then, under the optimal operating
      conditions (current density: 10.0mAcm(-2), aeration rate: 1000mLmin(-1), initial
      pH: 2.8), the identification of degradation products of ARS was carried out by
      using GC-MS and HPLC, meanwhile its degradation pathway was proposed according to
      the intermediates. Considering the location, intensity and intensity ratio of
      fluorescence center peak of the ARS in aqueous solution, a convenient and quick
      monitoring method by using excitation-emission matrix fluorescence spectrum
      technology was developed to monitor the degradation degree of ARS through electro
      Fenton process. Furthermore, it is suggested that the developed method would be
      promising for the quick analysis and evaluation of the degradation degree of the
      pollutants with pi-conjugated system. 

PMID- 24125711
TI  - Isolation and characterisation of azoxystrobin degrading bacteria from soil.
AB  - The first strobilurin fungicides were introduced in 1996, and have since been
      used in a vast array of disease/plant systems worldwide. The strobilurins now
      consist of 16 compounds and represent the 2nd most important fungicide group
      worldwide with 15% of the total fungicide market share. Strobilurins are
      moderately persistent in soil, and some degradation products (e.g. azoxystrobin
      acid) have been detected as contaminants of freshwater systems. Little is
      currently known about the transformation processes involved in the biodegradation
      of strobilurins or the microbial groups involved. Using sequential soil and
      liquid culture enrichments, we isolated two bacterial strains which were able to
      degrade the most widely used strobilurin, azoxystrobin, when supplied as a sole
      carbon source. 16S rRNA showed that the strains showed homology to Cupriavidus
      sp. and Rhodanobacter sp. Both isolated strains were also able to degrade the
      related strobilurin compounds trifloxystrobin, pyraclostrobin, and kresoxim
      methyl. An additional nitrogen source was required for degradation to occur, but
      the addition of a further carbon source reduced compound degradation by
      approximately 50%. However, (14)C radiometric analysis showed that full
      mineralisation of azosxystrobin to (14)CO2 was negligible for both isolates. 16S
      rRNA T-RFLP analysis using both DNA and RNA extracts showed that degradation of
      azoxystrobin in soil was associated with shifts in bacterial community structure.
      However, the phylotypes which proliferated during degradation could not be
      attributed to the isolated degraders. 

PMID- 24125712
TI  - Effects of suspended common-scale and nanoscale particles on the survival, growth
      and reproduction of Daphnia magna.
AB  - Suspended particles are a natural component of aquatic ecosystems. This study
      provides a report on the survival, growth and reproduction of common-scale and
      nanoscale particles of Daphnia magna Straus exposed to five types of particles
      (i.e. KN (kaolinite), MN (montmorillonite), MNn (nanoscale MN), NP (natural
      particles), and NPn (nanoscale NP)). The results of the study show that the
      suspended particles elicited a dose-dependent toxicity in KN, MN and MNn, with
      the following toxicity pattern: MN>KN>MNn. On the contrary, NP and NPn did not
      show any harmful effects on the animals. Instead, NP and NPn, especially NPn,
      contributed to the survivorship of the animals. The animals were able to survive
      throughout the 21-day period of bioassays, and when the particle concentration
      reached 600 mg L(-1), they produced many neonates without any addition of food.
      This experimental results also indicated that the nanoscale particles were less
      toxic than the common-scale ones, both for MN and NP. Moreover, the results of
      the 21-day period of bioassays indicated that when the organisms were exposed to
      particles of different size scales, they showed different selection patterns for
      allocating resources. This may be due to the generation of different assimilation
      and digestion patterns.

PMID- 24125713
TI  - Setting the most robust effluent level under severe uncertainty: application of
      information-gap decision theory to chemical management.
AB  - Decisions in ecological risk management for chemical substances must be made
      based on incomplete information due to uncertainties. To protect the ecosystems
      from the adverse effect of chemicals, a precautionary approach is often taken.
      The precautionary approach, which is based on conservative assumptions about the
      risks of chemical substances, can be applied selecting management models and
      data. This approach can lead to an adequate margin of safety for ecosystems by
      reducing exposure to harmful substances, either by reducing the use of target
      chemicals or putting in place strict water quality criteria. However, the
      reduction of chemical use or effluent concentrations typically entails a
      financial burden. The cost effectiveness of the precautionary approach may be
      small. Hence, we need to develop a formulaic methodology in chemical risk
      management that can sufficiently protect ecosystems in a cost-effective way, even
      when we do not have sufficient information for chemical management. Information
      gap decision theory can provide the formulaic methodology. Information-gap
      decision theory determines which action is the most robust to uncertainty by
      guaranteeing an acceptable outcome under the largest degree of uncertainty
      without requiring information about the extent of parameter uncertainty at the
      outset. In this paper, we illustrate the application of information-gap decision
      theory to derive a framework for setting effluent limits of pollutants for point
      sources under uncertainty. Our application incorporates a cost for reduction in
      pollutant emission and a cost to wildlife species affected by the pollutant. Our
      framework enables us to settle upon actions to deal with severe uncertainty in
      ecological risk management of chemicals. 

PMID- 24125714
TI  - The effect of granular ferric hydroxide amendment on the reduction of nitrate in
      groundwater by zero-valent iron.
AB  - The feasibility of using granular ferric hydroxide (GFH) with zero-valent iron
      (Fe(0)) for its potential utility in enhancing nitrate reduction was
      investigated. The addition of 10gL(-1) GFH to 25gL(-1) Fe(0) significantly
      enhanced nitrate removal, resulting in 93% removal of 52.2mg-NL(-1) in 36-h as
      compared to 23% removal with Fe(0) alone. Surface analyses of the reacted
      Fe(0)/GFH revealed the presence of magnetite on the Fe(0) surface, which probably
      served as an electron mediator for nitrate reduction. Addition of GFH to Fe(0)
      also resulted in lower solution pH compared to Fe(0). The rate enhancing effect
      of GFH on nitrate reduction was attributed to the combined effects of magnetite
      formation and pH buffering by GFH. GFH amendment (100gL(-1)) significantly
      increased reduction capacity and longevity of Fe(0) to complete several nitrate
      reduction cycles before inactivation, giving a total nitrate removal of 205mg-NL(
      1), while unamended Fe(0) gave only 20mg-NL(-1) before inactivation during the
      first reduction cycle. The overall result demonstrated the potential utility of
      Fe(0)/GFH system that may be developed into a viable technology for removal of
      nitrate from groundwater. 

PMID- 24125715
TI  - Enhanced removal of dichloroacetonitrile from drinking water by the combination
      of solar-photocatalysis and ozonation.
AB  - In this study, the photocatalytic ozonation process using either UV lamps with a
      wavelength close to a solar wavelength (UVsolar) or natural solar light was
      established to study the effects of the major operating parameters on the removal
      of a toxic disinfection by-product (DBP), dichloroacetonitrile (DCAN), from
      drinking water. Based on the test results of a bench system, the UVsolar/TiO2/O3
      process had the highest DCAN-removal rate among the advanced oxidation processes
      (AOPs). The optimal TiO2 and ozone doses were 1gL(-1) and 1.13gL(-1)h(-1),
      respectively, while room temperature (20 degrees C) produced the highest rate
      constant in the kinetic tests. The kinetic rate constants linearly increased when
      the UVsolar intensity increased in the range 4.6-25Wm(-2); however, it increased
      less at intensities higher than 25Wm(-2). The test results of the outdoor system
      showed that the solar/TiO2/O3 process provided complete removal of DCAN that was
      two times faster and had about 4.6 times higher energy efficiency than with
      solar/TiO2. As a green oxidation technique, solar photocatalytic ozonation could
      be a good alternative for treating recalcitrant and toxic organic pollutants,
      because it has high oxidation potential and low energy consumption compared to
      conventional AOPs. 

PMID- 24125716
TI  - Efficient degradation of contaminants of emerging concerns by a new electro
      Fenton process with Ti/MMO cathode.
AB  - The performance of a new electro-Fenton process with Ti-based mixed metal oxides
      (Ti/MMO) cathode, a dimensionally stable electrode, is evaluated for degrading
      contaminants of emerging concerns (CECs) in aqueous solutions. Bisphenol A
      (422MUgL(-1)) is completely degraded in an undivided cell using Ti/MMO as the
      cathode in the presence of 6.9mgL(-1) Fe(2+) within 20min under conditions of pH
      4 and 25mA. Both bisphenol A degradation and H2O2 production increase with
      decreasing solution pH and increasing current. Ti/MMO cathode is effective for
      reducing O2 to H2O2 and regenerating Fe(2+) from Fe(3+). OH radicals are
      validated to be the predominant reactive oxygen species (ROS) contributing to
      bisphenol A degradation. This new electro-Fenton process is also effective for
      degrading bisphenol A, triclosan and ibuprofen even at a relatively high
      concentration of 5mgL(-1). The partial removals of total organic carbon suggest a
      moderate extent of mineralization. The transformation pathways of the three CECs
      are proposed based on the intermediates identified by HPLC and GC-MS, showing
      that CECs are mainly transformed to nontoxic aliphatic acids. This study
      demonstrates that Ti/MMO can be used as the cathode in the electro-Fenton process
      for degrading CECs at trace levels in waters. 

PMID- 24125717
TI  - Chemical and photochemical degradation of chlorantraniliprole and
      characterization of its transformation products.
AB  - This study aimed at assessing the photodegradation of the insecticide
      chlorantraniliprole (CAP) in deionized water and in tap water amended with humic
      acids and nitrate. Photolysis was carried out under simulated solar or UV-A
      light. CAP (39 MUM) photodegradation was slightly faster in tap water than in
      deionized water with half lives of 4.1 and 5.1 days, respectively.
      Photodegradation rate of CAP was hardly affected by humic acids (up to 100 mg L(
      1)) and nitrate. Photodegradation pattern was different in slightly acidic
      (pH=6.1) deionized water compared to basic (pH=8.0) tap water. Four main
      degradation products have been isolated and characterized spectroscopically, and
      crystal structure was recorded for the first two photodegradation products. CAP
      also degraded in the dark controls, but only at basic pH (23% loss at pH 8.0 in
      tap water after 6 days), resulting in the formation of one single degradation
      product. Our study shows that the degradation of chlorantraniliprole in water is
      a combination of chemical and photochemical reactions, which are highly dependent
      on the pH of the solution.

PMID- 24125718
TI  - Dialysis experiments for assessing the pH-dependent sorption of sulfonamides to
      soil clay fractions.
AB  - Equilibrium dialysis experiments, a novel approach for conducting soil/water
      distribution experiments in environmental samples, were found to be applicable
      for assessing pH-dependent partitioning and to quantify the sorption of three
      sulfonamides, sulfadiazine, sulfadoxine, and sulfacetamide. Clay fractions from
      two agricultural soils including both particulate and dissolved soil matter were
      used in the experiments to achieve a high sorption capacity when varying pH in a
      relevant environmental range. Stabilizing and controlling pH was done by using
      organic buffers. In two clay fractions, Kd for sulfadiazine was determined to be
      43 and 129 L kg(-1), and 1.3 and 4.6 L kg(-1) at pH 4.0 and pH 9.0, respectively.
      This corresponded to Kd for the neutral and ionized form of sulfadiazine,
      respectively. The difference in sulfadiazine sorption between the two clay
      fractions could to some extent be related to the difference in the amount of
      organic carbon. Sorption experiments with sulfacetamide and sulfadoxine also
      exhibited decreasing sorption when increasing pH. At low pH, maximum Kd for
      sulfacetamide and sulfadoxine was determined to be 83 and 211 L kg(-1),
      respectively, while at high pH minimum Kd was 4.8 and 1.2 L kg(-1), respectively.
      Hence, compound speciation was important for the quantity of sorbed sulfonamide,
      which was confirmed by a correlation (R(2)) close to unity, when using the
      experimentally obtained Kd values with a simple model weighing the contribution
      from the neutral and the ionized compound, respectively.

PMID- 24125719
TI  - Characterization and quantification of N-(3-aminopropyl)-N-dodecyl-1,3
      propanediamine biocide by NMR, HPLC/MS and titration techniques.
AB  - The present paper reports the determination of the tri-amine N-(3-aminopropyl)-N
      dodecyl-1,3-propanediamine (TA) present in a raw material called LONZABAC used to
      formulate various, widely used commercial biocides. The active principle, TA, is
      present in LONZABAC together with other molecules at lower concentration levels.
      Three independent analytical approaches, namely solution NMR spectroscopy, liquid
      chromatography coupled to high resolution mass spectrometry (LC/HRMS) and acid
      base titration in mixed solvent, were used to overcome the problem of the non
      availability of the active principle as high purity standard. NMR analysis of raw
      material, using a suitable internal standard, evidenced in all analyzed lots the
      presence of the active principle, the N-dodecyl-1,3-propanediamine (DA) and the n
      dodecylamine (MA) and the absence of non-organic, NMR-inactive species. NMR peak
      integration led to a rough composition of the MA:DA:TA as 1:9:90. The LC/HRMS
      analysis allowed the accurate determination of DA and MA and confirmed in all
      samples the presence of the TA, which was estimated by difference: MA=1.4+/-0.3%,
      DA=11.1+/-0.7%, TA=87.5+/-1.3%. The obtained results were used to setup an easy,
      rapid and cheap acid-base titration method able to furnish a sufficiently
      accurate evaluation of the active principle both in the raw material and in
      diluted commercial products. For the raw material the results were: TA+MA=91.1+/
      0.8% and DA-MA=8.9+/-0.8%, statistically coherent with LC/MS ones. The LC/MS
      approach demonstrated also its great potentialities to recognize trace of the
      biocide components both in environmental samples and in the formulated commercial
      products.

PMID- 24125720
TI  - Possible involvement of Hcn1 ion channel in learning and memory dysfunction in
      SAMP8 mice.
AB  - The senescence-accelerated mouse prone 8 (SAMP8) strain exhibits age-related
      learning and memory deficits (LMD) at 2 months of age. Combined linkage analysis
      of 264 F2 intercross SAMP8 * JF1 mice and RNA-seq analysis identified Hcn1 gene
      out of 29 genes in the LMD region on chromosome 13. Hcn1 in SAMP8 strain showed
      15 times less polyglutamine repetition compared to Japanese fancy mouse 1 (JF1).
      Whole cell patch clamp analysis showed that Hcn1 ion conductivity was
      significantly lower in SAMP8 compared to that of JF1, which may be associated
      with learning and memory deficiency.

PMID- 24125721
TI  - Identification of Rorbeta targets in cultured osteoblasts and in human bone.
AB  - Control of osteoblastic bone formation involves the cumulative action of numerous
      transcription factors, including both activating and repressive functions that
      are important during specific stages of differentiation. The nuclear receptor
      retinoic acid receptor-related orphan receptor beta (Rorbeta) has been recently
      shown to suppress the osteogenic phenotype in cultured osteoblasts, and is highly
      upregulated in bone marrow-derived osteogenic precursors isolated from aged
      osteoporotic mice, suggesting Rorbeta is an important regulator of osteoblast
      function. However the specific gene expression patterns elicited by Rorbeta are
      unknown. Using microarray analysis, we identified 281 genes regulated by Rorbeta
      in an MC3T3-E1 mouse osteoblast cell model (MC3T3-Rorbeta-GFP). Pathway analysis
      revealed alterations in genes involved in MAPK signaling, genes involved in
      extracellular matrix (ECM) regulation, and cytokine-receptor interactions.
      Whereas the identified Rorbeta-regulated ECM genes normally decline during
      osteoblastic differentiation, they were highly upregulated in this non
      mineralizing MC3T3-Rorbeta-GFP model system, suggesting that Rorbeta may exert
      its anti-osteogenic effects through ECM disruption. Consistent with these in
      vitro findings, the expression of both RORbeta and a subset of RORbeta-regulated
      genes were increased in bone biopsies from postmenopausal women (73+/-7 years
      old) compared to premenopausal women (30+/-5 years old), suggesting a role for
      RORbeta in human age-related bone loss. Collectively, these data demonstrate that
      Rorbeta regulates known osteogenic pathways, and may represent a novel
      therapeutic target for age-associated bone loss.

PMID- 24125722
TI  - VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits
      angiogenesis.
AB  - Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required
      for tumor growth and progression. The conventional VEGF-A isoforms have been
      considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated
      by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property,
      exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family
      VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed
      ovarian cancer cells. SKOV3 cells were transfected with pcDNA3.1 empty vector,
      pcDNA3.1-VEGF111b or pcDNA3.1-VEGF165b to collect conditioned mediums
      respectively. VEGF111b overexpression inhibits proliferation, migration and tube
      formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its
      downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The
      anti-angiogenic property depends on the six amino acids of exon 8b of the
      VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti
      angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit
      ovarian tumor growth. 

PMID- 24125723
TI  - Italian albumin usage (or misusage?).

PMID- 24125724
TI  - The Mugello study, a survey of nonagenarians living in Tuscany: design, methods
      and participants' general characteristics.
AB  - BACKGROUND: Previous studies on nonagenarians have widely investigated functional
      and cognitive decline, falls, predictors of mortality, inflammation and aging
      genetics. However, some intriguing domains, such as body composition, daily
      energy expenditure, sleep quality and physical activity, as well as endothelial
      progenitor cells and "omics" fields, such as proteomics or metabolomics, have
      been poorly explored. In this preliminary paper we report design, methods and
      characteristics of participants in the Mugello Study, a survey of nonagenarians
      aimed at filling these gaps. METHODS: 475 non selected nonagenarians, 130 men and
      345 women, mean age 92.6 years +/- SD 2.6, received a visit by a trained
      physician at their residence. Along with the assessment of social, functional and
      cognitive status, reported in this paper, participants also underwent
      instrumental examinations, including body impedance assessment and continuous
      direct calorimetry, and were administered a series of validated questionnaires.
      Further, 385 participants accepted to undergo blood withdrawal. RESULTS: In 52
      cases the visit was conducted in nursing homes. Among the 423 home-living
      participants, 91 lived alone and 77 were not looked after by any caregiver.
      Altogether, 154 participants over 475 were free from disabilities and 266 showed
      Mini Mental State Examination raw scores >= 21. Men showed less disability and
      cognitive impairment (p<0.001, for both). CONCLUSIONS: As a whole, our findings
      are comparable to those reported in other surveys. Future studies, by using the
      Mugello Study database and biologic bank, that will be available to all
      researchers, will shed some more light on the aging process in nonagenarians.

PMID- 24125725
TI  - Endocrine changes, timing of ovulation, ovarian follicular growth and efficacy of
      a novel protocol (Estradoublesynch) for synchronization of ovulation and timed
      artificial insemination in Murrah buffaloes (Bubalus bubalis).
AB  - Experiments were conducted to investigate (1) ovarian follicular growth, timing
      of ovulation and associated endocrine changes (progesterone, estrogen, and LH) in
      cycling, and (2) efficacy in terms of pregnancy rate in cycling and anestrus
      Murrah buffaloes subjected to the Estradoublesynch protocol (prostaglandin
      F2alpha [PGF2alpha] 0, GnRH 2, PGF2alpha 9, estradiol benzoate, EB 10). Twelve
      cycling buffaloes were subjected to the Estradoublesynch protocol and observed
      for ovulation, follicle size, and endocrine changes after EB treatment. Ovulation
      occurred in 12 of 12 buffaloes (100%) at 48.5 +/- 1.6 hours (range, 38.0-56.0)
      after EB treatment. Plasma LH, total estrogen, and progesterone concentrations
      were determined in intensive blood samples collected after EB treatment. Peak LH
      concentration of 34.2 +/- 7.7 ng/mL (range, 17.8-178.5) occurred at 18.3 +/- 0.8
      hours (range, 14.0-22.0) after EB treatment. Peak total estrogen of 50.8 +/- 6.9
      pg/mL (range, 32.3-82.7) occurred 5.7 +/- 1.0 hours (range, 2.0-14.0) after EB
      treatment. Follicle size was gradually increased from second PGF2alpha injection
      (9.7 +/- 0.3 mm; range, 8.0-12.0) until ovulation was detected (12.9 +/- 0.4 mm;
      range, 11.0-15.0). Fourteen cycling and 11 anestrus buffaloes were subjected to
      the Estradoublesynch protocol, with timed artificial insemination (TAI) 48 and 60
      hours after EB treatment, and 58 cycling buffaloes were inseminated after
      spontaneous estrus (control group). Pregnancy rates were 62% for TAI of cycling
      buffaloes, 64% for anestrus buffaloes, and 34.5% for control group. Our
      observations demonstrated that the Estradoublesynch protocol followed by TAI
      satisfactory enhanced pregnancy rates in both cycling and anestrus buffaloes. 

PMID- 24125726
TI  - Predictors of pulmonary hypertension after intermediate-to-high risk pulmonary
      embolism.
AB  - BACKGROUND: Pulmonary embolism (PE) is a common cardiovascular emergency that,
      when combined with chronic thromboembolic pulmonary hypertension (PH), is
      associated with high mortality and morbidity. We aimed to determine the incidence
      of and predisposing factors for the development of PH after a PE episode.
      METHODS: A retrospective study was conducted in 213 patients admitted to an
      intensive care unit with intermediate-to-high risk PE between 2000 and 2010.
      Clinical data at admission were collected and the incidence of PH as assessed by
      echocardiography (estimated pulmonary systolic artery pressure over 40 mmHg) was
      determined. Multivariate analysis was used to determine predictors of development
      of PH. RESULTS: PH was detected in 12.4% of patients after a mean follow-up of
      three years. Only age (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.02
      1.20 per year; p=0.012) and body mass index (HR 1.19, 95% CI 1.04-1.36) per
      kg/m2, p=0.013) emerged as independent predictors of the development of this
      complication during follow-up. CONCLUSIONS: PH after PE was a relatively common
      complication in our series. We identified advanced age and increased body mass
      index as predisposing factors.

PMID- 24125727
TI  - A systematic review of interventions for preventing adolescent intimate partner
      violence.
AB  - PURPOSE: Intimate partner violence (IPV) is a pervasive global health issue
      affecting adolescents. We reviewed randomized controlled trials of interventions
      to reduce physical, sexual, and psychological violence perpetration and
      victimization among adolescents. METHODS: PUBMED, CINAHL, Science Direct, EMbase,
      PsychLIT, ISI Web of Science, Scopus, and the Cochrane database were searched for
      English language papers published up to the end of February 2013. RESULTS: Eight
      articles reporting on six randomized controlled trials were retrieved. Four
      interventions contained both school and community components. We found positive
      intervention effects on IPV perpetration (three studies) and IPV victimization
      (one study). Compared with the studies with no effects on IPV, the effective
      interventions were of longer duration, and were implemented in more than one
      setting. There were quality issues in all six trials. CONCLUSION: Interventions
      targeting perpetration and victimization of IPV among adolescents can be
      effective. Those interventions are more likely to be based in multiple settings,
      and focus on key people in the adolescents' environment. Future trials should
      assess perpetration and victimization of IPV among male and female adolescents
      with and without prior experiences with IPV, taking gender differences into
      account.

PMID- 24125728
TI  - Vinylbenzyl quaternary ammonium-based polymeric monolith with hydrophilic
      interaction/strong anion exchange mixed-mode for pressurized capillary
      electrochromatography.
AB  - A novel polymeric monolith with hydrophilic interaction and strong anion-exchange
      mixed-mode has been fabricated for pressurized capillary electrochromatography by
      an in situ copolymerization of vinylbenzyl trimethylammonium chloride (VBTA) and
      bisphenol A glycerolate dimethacrylate (BisGMA). The optimization of the
      polymerization mixture composition has been investigated, and column
      characteristics in terms of mechanical stability, permeability and
      reproducibility have been studied in detail. Linear responses between back
      pressure and flow rate have been achieved in different solvents. The absolute
      value of swelling propensity (SP) factor for poly(VBTA-co-BisGMA) monolith is
      0.41, and the degree of permeability drop from pure ACN to water is about 45%. An
      acceptable mechanical stability of the column is obtained. The suitable
      reproducibility is also measured with the RSD for day-to-day (n=3) of retention
      time and column efficiency less than 3.3%, and the RSD for batch-to-batch (n=3)
      less than 5.3%, respectively. Under the optimum conditions, the mixed-mode of
      hydrophilic interaction and strong anion-exchange has been carried out, and
      efficient electrochromatography profiling of various polar compounds including
      neutral phenols, negatively charged benzoic acids and positively charged nucleic
      acid bases and nucleosides are achieved, respectively. 

PMID- 24125729
TI  - Citrate versus heparin lock for hemodialysis catheters: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Citrate solution has been suggested as an effective and safe catheter
      lock in hemodialysis. However, whether a citrate lock is superior to a heparin
      lock in preventing catheter-related infections and maintaining catheter patency
      is inconclusive. STUDY DESIGN: A systematic review and meta-analysis was
      performed by searching in PubMed, EMBASE, Ovid, the Cochrane Library, and Web of
      Science databases and major nephrology journals. SETTING & POPULATION: Patients
      receiving hemodialysis with central venous catheters. SELECTION CRITERIA FOR
      STUDIES: Randomized controlled trials comparing citrate locks with heparin locks
      in hemodialysis patients with central venous catheters. INTERVENTION: Locking
      central venous catheters with citrate locks. OUTCOMES: Primary outcomes include
      catheter-related bloodstream infection (CRBSI), exit-site infection, catheter
      removal for poor flow, and thrombolytic treatment. RESULTS: 13 randomized
      controlled trials (1,770 patients, 221,064 catheter-days) met the inclusion
      criteria. Pooled analyses found that citrate locks could significantly reduce the
      incidence of CRBSI (risk ratio [RR], 0.39; 95% CI, 0.27-0.56; P < 0.001).
      Subgroup analysis showed that antimicrobial-containing citrate locks (citrate +
      gentamicin, citrate + taurolidine, and citrate + methylene blue + methylparaben +
      propylparaben) were superior to heparin locks in the prevention of CRBSI (P <
      0.001, P = 0.003, and P = 0.008, respectively), whereas citrate alone failed to
      show a similar advantage (P = 0.2). Low- (1.04%-4%) to moderate-concentration
      (4.6%-7%) citrate locks were associated with decreased CRBSI incidence (P < 0.001
      and P = 0.003, respectively), but patients receiving high-concentration (30%
      46.7%) citrate and heparin locks had similar incidences (P = 0.3). The incidence
      of bleeding episodes (RR, 0.48; 95% CI, 0.30-0.76; P = 0.002) was significantly
      lower in patients receiving citrate locks, whereas both groups were similar in
      terms of exit-site infection (P = 0.2), catheter removal for poor flow (P = 0.9),
      thrombolytic treatment (P = 0.8), all-cause death (P = 0.3), catheter thrombosis
      (P = 0.9), mean catheter duration (P = 0.2), CRBSI-free catheter survival (P =
      0.2), and catheter-related readmission (P = 0.5). LIMITATIONS: All studies used
      in the meta-analysis were performed in Western countries. The applicability of
      our findings to other regions remains to be clarified. CONCLUSIONS: An
      antimicrobial-containing citrate lock is better than a heparin lock in the
      prevention of catheter-related infection, while citrate alone fails to show a
      similar advantage. Citrate locks of low to moderate concentrations, rather than
      high concentration, were superior to heparin locks in preventing CRBSI. Citrate
      locks also might decrease bleeding episodes. No difference has been identified in
      the efficacy to prevent exit-site infection or preserve catheter patency between
      citrate and heparin locks.

PMID- 24125731
TI  - Comparative metabolomics of estrogen receptor positive and estrogen receptor
      negative breast cancer: alterations in glutamine and beta-alanine metabolism.
AB  - Molecular subtyping of breast cancer is necessary for therapy selection and
      mandatory for all breast cancer patients. Metabolic alterations are considered a
      hallmark of cancer and several metabolic drugs are currently being investigated
      in clinical trials. However, the dependence of metabolic alterations on breast
      cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen
      receptor positive (ER+) and 67 estrogen receptor negative (ER-) breast cancer
      tissues were investigated using GC-TOFMS based metabolomics. 19 metabolites were
      detected as altered in a predefined training set (2/3 of tumors) and could be
      validated in a predefined validation set (1/3 of tumors). The metabolite changes
      included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and
      decreases in glutamine in the ER- subtype. Beta-alanine demonstrated the
      strongest change between ER- and ER+ breast cancer (fold change=2.4, p=1.5E-20).
      In a correlation analysis with genome-wide expression data in a subcohort of 154
      tumors, we found a strong negative correlation (Spearman R=-0.62) between beta
      alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis
      confirmed down-regulation of the ABAT protein in ER- breast cancer. In a Kaplan
      Meier analysis of a large external expression data set, the ABAT transcript was
      demonstrated to be a positive prognostic marker for breast cancer (HR=0.6, p=3.2E
      15). BIOLOGICAL SIGNIFICANCE: It is well-known for more than a decade that breast
      cancer exhibits distinct gene expression patterns depending on the molecular
      subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that
      breast cancer exhibits distinct metabolomics patterns depending on ER status. Our
      observation supports the current view of ER+ breast cancer and ER- breast as
      different diseases requiring different treatment strategies. Metabolic drugs for
      cancer including glutaminase inhibitors are currently under development and
      tested in clinical trials. We found glutamate enriched and glutamine reduced in
      ER- breast cancer compared to ER+ breast cancer and compared to normal breast
      tissues. Thus, metabolomics analysis highlights the ER- subtype as a preferential
      target for glutaminase inhibitors. For the first time, we report on a regulation
      of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript
      expression was variable and correlated with ER status. Low ABAT transcript
      expression was associated with low ABAT protein expression and high beta-alanine
      concentration. In a large external microarray cohort, low ABAT expression
      shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER-
      breast cancer.

PMID- 24125730
TI  - Proteomic protease specificity profiling of clostridial collagenases reveals
      their intrinsic nature as dedicated degraders of collagen.
AB  - Clostridial collagenases are among the most efficient degraders of collagen. Most
      clostridia are saprophytes and secrete proteases to utilize proteins in their
      environment as carbon sources; during anaerobic infections, collagenases play a
      crucial role in host colonization. Several medical and biotechnological
      applications have emerged utilizing their high collagenolytic efficiency.
      However, the contribution of the functionally most important peptidase domain to
      substrate specificity remains unresolved. We investigated the active site
      sequence specificity of the peptidase domains of collagenase G and H from
      Clostridium histolyticum and collagenase T from Clostridium tetani. Both prime
      and non-prime cleavage site specificity were simultaneously profiled using
      Proteomic Identification of protease Cleavage Sites (PICS), a mass spectrometry
      based method utilizing database searchable proteome-derived peptide libraries.
      For each enzyme we identified >100 unique-cleaved peptides, resulting in robust
      cleavage logos revealing collagen-like specificity patterns: a strong preference
      for glycine in P3 and P1', proline at P2 and P2', and a slightly looser
      specificity at P1, which in collagen is typically occupied by hydroxyproline.
      This specificity for the classic collagen motifs Gly-Pro-X and Gly-X-Hyp
      represents a remarkable adaptation considering the complex requirements for
      substrate unfolding and presentation that need to be fulfilled before a single
      collagen strand becomes accessible for cleavage. BIOLOGICAL SIGNIFICANCE: We
      demonstrate the striking sequence specificity of a family of clostridial
      collagenases using proteome derived peptide libraries and PICS, Proteomic
      Identification of protease Cleavage Sites. In combination with the previously
      published crystal structures of these proteases, our results represent an
      important piece of the puzzle in understanding the complex mechanism underlying
      collagen hydrolysis, and pave the way for the rational design of specific test
      substrates and selective inhibitors. This article is part of a Special Issue
      entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

PMID- 24125732
TI  - Autoantibody recognition of an N-terminal epitope of hnRNP L marks the risk for
      developing HBV-related hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is associated with a poor prognosis and remains
      one of the leading causes of cancer death worldwide. Tumor-associated antigens
      (TAAs) and autoantibodies have been reported as potential markers in different
      cancers. Here, we employed an immunoproteomic approach to identify TAAs in the
      sera of patients with hepatitis B virus-related HCC (HBV-HCC). Immunoreactive
      spots were excised from 2-DE and analyzed by nano-LC-MS/MS. This analysis
      identified 16 HCC-associated antigens, including hnRNP L. The antigenicity of
      hnRNP L was further validated by immunoblotting using recombinant proteins.
      Autoantibodies against hnRNP L were found in 60% patients with HBV-HCC. Using
      sera from hnRNP L-positive patients, we found that most of these antibodies
      recognized glycine-rich region in the N-terminus of hnRNP L. In addition, high
      titers of autoantibodies against hnRNP L were found in HBV-HCC patients' sera and
      were associated with increased tumor size and reduced survival rate. hnRNP L
      protein was also found highly expressed in HCC tissue. Knockdown of hnRNP L
      significantly suppressed cell growth, migration, and invasion in vitro. Our
      results indicate that an N-terminal epitope of hnRNP L is a potential biomarker
      for the diagnosis of HBV-HCC and show that hnRNP L contributes to HCC
      progression. BIOLOGICAL SIGNIFICANCE: In this paper, we employed an
      immunoproteomic approach to identify TAAs in the sera of patients with hepatitis
      B virus-related HCC (HBV-HCC). We identified hnRNP L as a tumor-associated
      antigen in HBV-relative HCC patients. Glycine-rich region located at the N
      terminus of hnRNP L constitutes the major epitope. We also demonstrated that
      hnRNP L is involved in cell proliferation and metastasis.

PMID- 24125733
TI  - Cholesterol to cholestenone oxidation by ChoG, the main extracellular cholesterol
      oxidase of Rhodococcus ruber strain Chol-4.
AB  - The choG ORF of Rhodococcus ruber strain Chol-4 (referred from now as Chol-4)
      encodes a putative extracellular cholesterol oxidase. In the Chol-4 genome this
      ORF is located in a gene cluster that includes kstD3 and hsd4B, showing the same
      genomic context as that found in other Rhodococcus species. The putative ChoG
      protein is grouped into the class II of cholesterol oxidases, close to the
      Rhodococcus sp. CECT3014 ChoG homolog. The Chol-4 choG was cloned and expressed
      in a CECT3014 DeltachoG host strain in order to assess its ability to convert
      cholesterol into cholestenone. The RT-PCR analysis showed that choG gene was
      constitutively expressed in all the conditions assayed, but a higher induction
      could be inferred when cells were growing in the presence of cholesterol. A Chol
      4 DeltachoG mutant strain was still able to grow in minimal medium supplemented
      with cholesterol, although at a slower rate. A comparative study of the removal
      of both cholesterol and cholestenone from the culture medium of either the wild
      type Chol-4 or its choG deletion mutant revealed a major role of ChoG in the
      extracellular production of cholestenone from cholesterol and, therefore, this
      enzyme may be related with the maintenance of a convenient supply of cholestenone
      for the succeeding steps of the catabolic pathway. 

PMID- 24125734
TI  - MART-10, a less calcemic vitamin D analog, is more potent than 1alpha,25
      dihydroxyvitamin D3 in inhibiting the metastatic potential of MCF-7 breast cancer
      cells in vitro.
AB  - With the recent advance in breast cancer therapy, the survival rate of breast
      cancer patients has improved greatly. In spite of the progress, 25-50% of breast
      cancer patients eventually will develop metastasis. Due to limited early
      detection methods, metastasis is usually diagnosed at the late stages beyond
      recovery likely due to resistance to currently available breast cancer therapies.
      Thus, a new strategy to prevent cancer cell growth and repress tumor metastasis
      is desirable. The active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3
      [1alpha,25(OH)2D3], has anti-invasion and anti-migration properties in pre
      clinical studies, yet its clinical application has been hampered by its
      hypercalcemic side effect. Previously, we have demonstrated that a new class of
      less-calcemic vitamin D analog, 19-nor-2alpha-(3-hydroxypropyl)-1alpha,25
      dihydroxyvitamin D3 (MART-10), is 1000-fold more active than 1alpha,25(OH)2D3 in
      suppressing MCF-7 cells growth through cell cycle arrest and apoptosis induction.
      In the current study, we show for the first time that MART-10 is more active than
      1alpha,25(OH)2D3 in preventing MCF-7 cell invasion and migration likely mediated
      through the upregulation of E-cadherin, and the downregulation of Snail, Slug,
      and Twist, the transcription factors implicated in epithelial-mesenchymal
      transition (EMT), as well as MMP-13. Based on the current in vitro and the highly
      anti-tumor characteristics of MART-10 in a pancreatic xenograft model, MART-10 is
      deemed as a promising candidate for breast cancer treatment. Further in vivo
      animal study comparing MART-10 with 1alpha,25(OH)2D3 and other potent and less
      calcemic analogs of vitamin D is warranted. 

PMID- 24125735
TI  - The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation.
AB  - Maintenance of an adequate vitamin D status, as indicated by the level of
      circulating 25-hydroxyvitamin D (25(OH)D), is associated with higher bone mass
      and decreased risk of fracture. However, the molecular actions of vitamin D
      hormone (1,25(OH)2D3) in bone are complex, and include stimulation of
      osteoclastogenesis via RANK-ligand up-regulation, as well as the inhibition of
      mineralisation. We hypothesise that these divergent data may be reconciled by
      autocrine actions of 1,25(OH)2D3 which effect skeletal maintenance, as opposed to
      endocrine 1,25(OH)2D3 which acts to maintain serum calcium homeostasis. We have
      previously described local metabolism of 1,25(OH)2D3 within osteoblasts, with
      effects on gene expression and cell function. The aim of the current study was to
      investigate potential autocrine actions of 1,25(OH)2D3 within cells that exhibit
      osteocyte-like properties. Late osteoblastic MLO-A5 cells were cultured in the
      presence of 25(OH)D for 9 days with gene expression analysed pre- and post
      mineralisation. Gene expression analysis revealed maturation within this time
      frame to an osteocyte-like stage, evidenced by increased Dmp1 and Phex mRNA
      expression. Expression of Cyp27b1 in 25(OH)D treated MLO-A5 cells was associated
      with elevated media levels of 1,25(OH)2D3 (p<0.05), induction of Cyp24a1
      (p<0.001) and elevated ratios of Opg:Rankl mRNA (p<0.01). Chronic 25(OH)D
      exposure also increased osteocalcin mRNA in MLO-A5 cells, which contrasted with
      the dose-dependent inhibition of osteocalcin mRNA observed with acute treatment
      in MLO-Y4 cells (p<0.01). Treatment of MLO-Y4 cells with 25(OH)D also inhibited
      Phex mRNA expression (p<0.05), whilst Enpp1 gene expression was induced (p<0.01).
      Overall, the current study demonstrates that osteocyte-like cells convert
      physiological levels of 25(OH)D to 1,25(OH)2D3, with changes in gene expression
      that are consistent with increased osteocyte maturation. Although the
      physiological role of local metabolism of 1,25(OH)2D3 within osteocytes requires
      further investigation, the abundance and diverse functions of this cell type
      within bone underscore its potential importance. This article is part of a
      Special Issue entitled '16th Vitamin D Workshop'. 

PMID- 24125736
TI  - Electropolymerized fluorinated aniline-based fiber for headspace solid-phase
      microextraction and gas chromatographic determination of benzaldehyde in
      injectable pharmaceutical formulations.
AB  - In this study, a simple method was developed and validated to detect trace levels
      of benzaldehyde in injectable pharmaceutical formulations by solid-phase
      microextraction coupled with gas chromatography-flame ionization detector.
      Polyaniline was electrodeposited on a platinum wire in trifluoroacetic acid
      solvent by cyclic voltammetry technique. This fiber shows high thermal and
      mechanical stability and high performance in extraction of benzaldehyde.
      Extraction and desorption time and temperature, salt effect and gas
      chromatography parameters were optimized as key parameters. At the optimum
      conditions, the fiber shows good linearity between peak area ratio of
      benzaldehyde/3-chlorobenzaldehyde and benzaldehyde concentration in the range of
      50-800 ng/mL with percent relative standard deviation values ranging from 0.75 to
      8.64% (n = 3). The limits of quantitation and detection were 50 and 16 ng/mL,
      respectively. The method has the requisite selectivity, sensitivity, accuracy and
      precision to assay benzaldehyde in injectable pharmaceutical dosage forms. 

PMID- 24125737
TI  - A SPME-GC/MS procedure for the determination of fatty acid ethyl esters in hair
      for confirmation of abstinence test results.
AB  - Fatty acid ethyl esters (FAEE), direct metabolites of ethanol, are suitable
      alcohol markers that can be detected in different tissues. The determination of
      FAEE in hair can help to evaluate social and excessive alcohol consumption. Due
      to the presence of FAEE in the hair of teetotalers, proving alcohol abstinence
      seems to be impossible. To verify these results, an solid phase micro extraction
      gas chromatography/mass spectrometry procedure for the determination of the four
      FAEE: ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate in hair
      was validated with special focus on low concentration levels. Besides very high
      sensitivity (limits of detection between 0.005 and 0.009 ng/mg), good results for
      linearity, precision and accuracy, recovery and stability were achieved. In
      addition, 73 hair samples with measured ethyl glucuronide (EtG) concentrations
      between 4 and 10 pg/mg were analyzed for FAEE. By using the following cut-offs:
      EtG: 7 pg/mg, FAEE: 0.2 ng/mg a satisfying matching rate of 72.6% was found. This
      shows that FAEE can be determined to verify borderline EtG concentrations even in
      the context of abstinence tests. However, the diversified influencing factors on
      analyte concentrations in hair, which may explain the large deviations between
      EtG and FAEE results observed in some cases, have to be mentioned when interpret
      ambiguous results. 

PMID- 24125738
TI  - Dabigatran in the setting of catheter ablation of atrial fibrillation: the road
      ahead.

PMID- 24125739
TI  - Associations of maternal 25-hydroxyvitamin D in pregnancy with offspring
      cardiovascular risk factors in childhood and adolescence: findings from the Avon
      Longitudinal Study of Parents and Children.
AB  - OBJECTIVE: Lower maternal vitamin D status in pregnancy may be associated with
      increased offspring cardiovascular risk in later life, but evidence for this is
      scant. We examined associations of maternal total 25-hydroxyvitamin D (25(OH)D)
      in pregnancy with offspring cardiovascular risk factors assessed in childhood and
      adolescence. DESIGN: A longitudinal, prospective study. SETTING: The study was
      based on data from mother-offspring pairs in the Avon Longitudinal Study of
      Parents and Children (ALSPAC), a UK prospective population-based birth cohort
      (N=4109). OUTCOME MEASURES: Offspring cardiovascular risk factors were measured
      in childhood (mean age 9.9 years) and in adolescence (mean age 15.4 years): blood
      pressure, lipids, apolipoproteins (at 9.9 years only), glucose and insulin (at
      15.4 years only), C reactive protein (CRP), and interleukin 6 (at 9.9 years only)
      were measured. RESULTS: After adjustments for potential confounders (maternal
      age, education, body mass index (BMI), smoking, physical activity, parity,
      socioeconomic position, ethnicity, and offspring gestational age at 25(OH)D
      sampling; gender, age, and BMI at outcome assessment), maternal 25(OH)D was
      inversely associated with systolic blood pressure (-0.48 mm Hg difference per 50
      nmol/L increase in 25(OH)D; 95% CI -0.95 to -0.01), Apo-B (-0.01 mg/dL
      difference; 95% CI -0.02 to -0.001), and CRP (-6.1% difference; 95% CI -11.5% to 
      0.3%) at age 9.9 years. These associations were not present for risk factors
      measured at 15.4 years, with the exception of a weak inverse association with CRP
      (-5.5% difference; 95% CI -11.4% to 0.8%). There was no strong evidence of
      associations with offspring triglycerides, glucose or insulin. CONCLUSIONS: Our
      findings suggest that fetal exposure to 25(OH)D is unlikely to influence
      cardiovascular risk factors of individuals later in life.

PMID- 24125740
TI  - Staffing and resource adequacy strongly related to RNs' assessment of patient
      safety: a national study of RNs working in acute-care hospitals in Sweden.
AB  - INTRODUCTION: Although registered nurses (RNs) are central in patient care, we
      have not found prior research that specifically addresses how RNs assess the
      safety of patient care at their workplace and how factors in RNs' work
      environment are related to their assessments. This study aims to address these
      issues. METHODS: 9236 RNs working with inpatient care in 79 acute-care hospitals
      in Sweden completed a national population-based survey, including Practice
      Environment Scale of the Nursing Work Index-Revised and items from Agency for
      Healthcare Research and Quality's Hospital Survey on Patient Safety Culture.
      Correlation coefficients (Pearson and Spearman) and proportional odds regression
      were used for analysis. RESULTS: Nursing work environment factors were strongly
      related to RNs' assessments of patient safety. RNs' perception of having adequate
      staffing and resources improved their assessment of patient safety by at least
      two and a half times (OR 2.74 CI 2.52 to 2.97). RNs with a higher level of
      involvement in direct patient care gave a better patient safety grade than RNs
      with a more supervisory role. Most, but not all, patient safety culture items
      were related to RNs' assessed patient safety grade. We found that work experience
      seemed to have no influence on RNs' patient safety assessment. CONCLUSIONS: While
      previous research emphasises patient-to-nurse ratios in strengthening patient
      safety practices, this study complements this by emphasising RNs' own perception
      of having enough staff and resources to provide quality nursing care, as well as
      having good collegial nurse-physician relations and the presence of visible and
      competent nursing leadership-all factors highly related to RNs' assessment of the
      safety of patient care at their workplace.

PMID- 24125741
TI  - Delay between symptom onset and clinic attendance following TIA and minor stroke:
      the BEATS study.
AB  - BACKGROUND: rapid specialist assessment of patients with transient ischaemic
      attack (TIA) reduces the risk of recurrent stroke. National guidelines advise
      that high-risk patients are assessed within 24 h and low-risk patients within 7
      days. AIM: to quantify delay and map pathways taken by patients from symptom
      onset to specialist assessment. DESIGN: retrospective cohort study. SETTING:
      rapid access TIA clinic. METHODS: structured interviews with 278 patients newly
      diagnosed with TIA (222) or minor stroke (56), and examination of medical
      records. RESULTS: of the 133 high-risk TIA patients, 11 (8%) attended the clinic
      within 24 h of symptom onset; of the 89 low-risk TIA patients, 47 (53%) attended
      within 7 days. Median delay between symptom onset and seeking help from a
      healthcare professional (HCP) was 4.0 h (IQR 0.5, 41.3). Delay was less if
      symptoms were correctly interpreted but not reduced by a publicity campaign
      (FAST) to encourage an urgent response. Most patients (156, 56%) first contacted
      a general practitioner (GP) and 46 (17%) called an ambulance or attended the
      emergency department. Over a third (36%) had a second consultation with an HCP
      before attending the clinic, and this was more likely in those presenting to
      paramedics, out of hours GP services or optometry. Time to clinic attendance was
      less if an emergency pathway was used and greater if patients were seen by a
      second HCP. CONCLUSIONS: factors contributing to delay include incorrect
      interpretation of symptoms and failure to invoke emergency services. Delays after
      presentation could be addressed by direct referral by out of hours services,
      paramedics and optometrists.

PMID- 24125742
TI  - Chest compression depth and survival in out-of-hospital cardiac arrest.
AB  - AIM: Outcomes from out-of-hospital cardiac arrest (OHCA) may improve if rescuers
      perform chest compressions (CCs) deeper than the previous recommendation of 38
      51mm and consistent with the 2010 AHA Guideline recommendation of at least 51mm.
      The aim of this study was to assess the relationship between CC depth and OHCA
      survival. METHODS: Prospective analysis of CC depth and outcomes in consecutive
      adult OHCA of presumed cardiac etiology from two EMS agencies participating in
      comprehensive CPR quality improvement initiatives. ANALYSIS: Multivariable
      logistic regression to calculate adjusted odds ratios (aORs) for survival to
      hospital discharge and favorable functional outcome. RESULTS: Among 593 OHCAs,
      136 patients (22.9%) achieved return of spontaneous circulation, 63 patients
      (10.6%) survived and 50 had favorable functional outcome (8.4%). Mean CC depth
      was 49.8+/-11.0mm and mean CC rate was 113.9+/-18.1CCmin(-1). Mean depth was
      significantly deeper in survivors (53.6mm, 95% CI: 50.5-56.7) than non-survivors
      (48.8mm, 95% CI: 47.6-50.0). Each 5mm increase in mean CC depth significantly
      increased the odds of survival and survival with favorable functional outcome:
      aORs were 1.29 (95% CI 1.00-1.65) and 1.30 (95% CI 1.00-1.70) respectively.
      CONCLUSION: Deeper chest compressions were associated with improved survival and
      functional outcome following OHCA. Our results suggest that adhering to the 2010
      AHA Guideline-recommended depth of at least 51mm could improve outcomes for
      victims of OHCA.

PMID- 24125743
TI  - Association of D2-40 and MMP-1 expression with cyst formation in lung metastatic
      lesions of cutaneous angiosarcoma on the scalp: immunohistochemical analysis of
      23 autopsy cases.
AB  - Cutaneous angiosarcoma of the scalp can rapidly develop into pulmonary
      metastasis. The pulmonary metastatic lesions display a unique appearance, so
      called thin-walled cysts, which cause a fatal relapsed pneumothorax by rupturing.
      We analyzed 23 autopsy cases of angiosarcoma with pulmonary metastasis to
      elucidate the mechanism of the thin-walled cyst development. Of the 23 cases of
      cutaneous angiosarcoma of the scalp with pulmonary metastasis, radiological
      examination revealed pulmonary metastatic lesions as thin-walled cysts (39%),
      nodules (39%), mixed cysts and nodules (13%), and ground-glass opacity (9%). All
      the cases but one with cystic metastases were complicated by pneumothorax. The
      cystic lesions were accompanied by podoplanin (D2-40)-positive tumor cells in the
      luminal surface of the cysts. In both primary cutaneous lesions and pulmonary
      metastatic lesions, the D2-40 expression was positive for angiosarcoma cells in
      100% and 92% of the cases, respectively. While the estrogen-regulated gene (ERG)
      expression was also positive for most of the primary and metastatic pulmonary
      angiosarcomas, D2-40 was a more useful marker to differentiate tumor cells from
      the background than was the ERG expression of the vascular endothelium. Matrix
      metalloproteinase-1 (MMP-1) expression was also predominant in primary lesions
      (95%) and pulmonary metastatic lesions (82.6%). Proteinases, like MMP-1, might be
      associated with a developing thin-walled cyst, although there were no differences
      in the MMP-1 expression in either the cystic or nodular metastasis. Two extremely
      aggressive cases showed cystic metastasis with central necrosis that was not
      observed in other cases. These results suggest a pathogenesis of thin-walled
      cysts in some progressive cases. 

PMID- 24125744
TI  - Smoking during pregnancy causes double-strand DNA break damage to the placenta.
AB  - Despite the adverse effects of smoking, many pregnancies are exposed to tobacco
      smoke. Recent studies have investigated whether smoking damages placental DNA by
      measuring DNA adducts. This study investigated whether a more severe lesion,
      double-strand DNA breaks, was also present in the tobacco smoking-exposed
      placenta. Term placentae from women who smoked during their entire pregnancies (n
      = 52), from those who had ceased smoking for at least 4 weeks before delivery
      (previous smokers, n = 34), and from nonsmoking women (n = 150) were examined
      using the DNA double-strand break marker phosphorylated gamma H2AX. The extent of
      DNA damage was assessed according to cell type and additional markers were
      applied for cell fate (apoptosis and DNA repair), and function (human chorionic
      gonadotropin, human placental lactogen, and glucose transporter 1), to
      characterize the effect of the DNA damage on placental integrity. Marked
      phosphorylated gamma H2AX-positive cells occurred in the villous
      syncytiotrophoblast and syncytial knot nuclei in placentae from smokers (P <
      .001). Phosphorylated gamma H2AX foci did not colocalize with the DNA repair
      protein 53BP1, and damaged nuclei had a marked reduction in expression of human
      chorionic gonadotropin, human placental lactogen, and glucose transporter 1.
      Minimal DNA damage, similar to nonsmokers, was present in previous smokers
      including those that had ceased smoking for just over 4 weeks before delivery. In
      summary, smoking during pregnancy was associated with marked double-strand DNA
      break damage to the syncytiotrophoblast. We suggest that smoking cessation is
      important to prevent additional DNA damage and to facilitate DNA repair. 

PMID- 24125745
TI  - Mushroom immunomodulators: unique molecules with unlimited applications.
AB  - For centuries, mushrooms have been used as food and medicine in different
      cultures. More recently, many bioactive compounds have been isolated from
      different types of mushrooms. Among these, immunomodulators have gained much
      interest based on the increasing growth of the immunotherapy sector. Mushroom
      immunomodulators are classified under four categories based on their chemical
      nature as: lectins, terpenoids, proteins, and polysaccharides. These compounds
      are produced naturally in mushrooms cultivated in greenhouses. For effective
      industrial production, cultivation is carried out in submerged culture to
      increase the bioactive compound yield, decrease the production time, and reduce
      the cost of downstream processing. This review provides a comprehensive overview
      on mushroom immunomodulators in terms of chemistry, industrial production, and
      applications in medical and nonmedical sectors. 

PMID- 24125746
TI  - Virus-like particle-based human vaccines: quality assessment based on structural
      and functional properties.
AB  - Human vaccines against three viruses use recombinant virus-like particles (VLPs)
      as the antigen: hepatitis B virus, human papillomavirus, and hepatitis E virus.
      VLPs are excellent prophylactic vaccine antigens because they are self-assembling
      bionanoparticles (20 to 60 nm in diameter) that expose multiple epitopes on their
      surface and faithfully mimic the native virions. Here we summarize the long
      journey of these vaccines from bench to patients. The physical properties and
      structural features of each recombinant VLP vaccine are described. With the
      recent licensure of Hecolin against hepatitis E virus adding a third disease
      indication to prophylactic VLP-based vaccines, we review how the crucial quality
      attributes of VLP-based human vaccines against all three disease indications were
      assessed, controlled, and improved during bioprocessing through an array of
      structural and functional analyses.

PMID- 24125747
TI  - Solitary plaque of the labial commissure with contiguous mucosal involvement: a
      distinct subset of porokeratosis?

PMID- 24125748
TI  - Single port gasless laparoscopy-assisted mini-laparotomic ovarian resection (SP
      GLAMOR): reasonable treatment for large cystic ovarian tumors with suspicion of
      malignancy.
AB  - OBJECTIVES: Recent improvements to both optical and laparoscopic instruments have
      enabled the use of laparoscopic surgery for gynecological procedures as opposed
      to open abdominal surgery. However, laparoscopic surgery has several potential
      limitations, including tumor rupture, spillage, incomplete resection of lesions,
      and trocar insertion site metastasis in surgeries involving large ovarian masses
      with suspicion of malignancy. Here, we report a case series of large ovarian
      cystic tumors that were successfully removed by single port gasless laparoscopy
      assisted mini-laparotomic ovarian resection (SP-GLAMOR), the limitations of which
      were successfully addressed. METHODS: We reviewed the medical records of 31 women
      who visited St. Vincent Hospital from April 2006 until April 2011 and were
      diagnosed with a large cystic ovarian mass with suspicion of malignancy based on
      imaging studies and tumor markers. After diagnosis, all of the women underwent SP
      GLAMOR. RESULTS: The median maximal diameter of cysts, median incision size,
      median surgical duration and median volume of blood loss were 20 cm (range 10.7
      45 cm), 3 cm (range 2.5-4 cm), 100 min (range 45-270 min) and 100mL (range 30-500
      mL), respectively. Four cases were diagnosed as malignant disease on frozen
      sections obtained during the operation, and were converted to open abdominal
      surgery. No major complications were observed. The four patients diagnosed with
      malignant disease also underwent adjuvant chemotherapy. All patients were
      followed up to the time of this report. CONCLUSIONS: The results of our study
      suggest that the SP-GLAMOR procedure is feasible, with potentially decreased
      perioperative morbidity and blood loss, faster recovery and better cosmetic
      results.

PMID- 24125749
TI  - The Wnt/beta-catenin pathway in ovarian cancer: a review.
AB  - OBJECTIVE: Ovarian cancer is the deadliest gynecologic malignancy and the fifth
      leading cause of death from cancer in women in the U.S. Since overall survival
      remains poor, there is a need for new therapeutic paradigms. This paper will
      review the Wnt/beta-catenin pathway as it relates to epithelial ovarian cancer,
      specifically its role in chemoresistance and its potential role as a target for
      chemosensitization. METHODS: A PubMed search was performed for articles published
      pertaining to Wnt/beta-catenin pathway specific to ovarian cancer. Wnt/beta
      catenin signaling pathways play an active role in cancer stem cells (CSCs) and
      carcinogenesis of all ovarian cancer subtypes. Studies also have shown that
      ovarian CSCs are involved in chemoresistance, metastasis, and tumor recurrence.
      RESULTS: Wnt/beta-catenin target genes regulate cell proliferation and apoptosis,
      thereby mediating cancer initiation and progression. The Wnt/beta-catenin pathway
      is one of the major signaling pathways thought to be involved in epithelial-to
      mesenchymal transition (EMT). Alterations affecting Wnt pathway proteins on the
      cell membrane, in the cytoplasm, and in the nucleus have been shown to play
      important roles in the tumorigenesis of ovarian cancer. CONCLUSIONS: Wnt
      signaling is activated in epithelial ovarian cancer. Given the role of the
      Wnt/beta-catenin pathway in carcinogenesis, more pre-clinical studies are
      warranted to further investigate other Wnt inhibitors in ovarian cancer. The Wnt
      pathway should also be investigated as a potential target in the development of
      new drugs for ovarian cancer as a single agent and in combination with
      chemotherapy or other targeted agents.

PMID- 24125750
TI  - Quality of life and treatment response among women with platinum-resistant versus
      platinum-sensitive ovarian cancer treated for progression: a prospective
      analysis.
AB  - OBJECTIVE: Most women with ovarian cancer relapse and undergo further
      chemotherapy however evidence regarding the benefits of this for women with
      platinum-resistant disease is limited. Our objective was to determine whether
      there was a quality of life improvement or treatment response among women treated
      for platinum-resistant recurrent ovarian cancer. METHODS: We combined data from 2
      studies where women treated with chemotherapy for recurrent ovarian cancer
      (n=172) completed a quality of life questionnaire every 3 months. Cancers were
      classified as platinum-resistant if they progressed within 6 months of completing
      first-line chemotherapy. Mixed effects models were used to analyze change in
      quality of life during the first 6 months after second-line chemotherapy.
      RESULTS: One-quarter of women (n=44) were classified as having platinum-resistant
      disease. Overall, their quality of life did not significantly increase or
      decrease, following commencement of second-line chemotherapy (least square mean
      scores=107, 105, 103 at chemotherapy start, 3 and 6 months later, respectively),
      although 26% of these women reported a meaningful increase and 31% reported a
      meaningful decline. One-third of the platinum-resistant group responded (11%
      complete and 21% partial response) to second-line chemotherapy, and this figure
      increased to 54% among the subset (36%) re-treated with platinum-based agents
      with or without other agents. Preliminary analyses suggest that quality of life
      may be higher at chemotherapy initiation in women whose disease responded (median
      score 121 vs 110). CONCLUSIONS: Overall, quality of life appears to be maintained
      in women with platinum-resistant ovarian cancer who receive further chemotherapy
      and some women respond to re-treatment.

PMID- 24125751
TI  - Lymphatic and nerve distribution throughout the parametrium.
AB  - BACKGROUND: Our objective was to concomitantly assess distribution of lymphatic
      and nerve structures in the parametrium. METHODS: Twenty hemipelvises from ten
      fresh cadavers were dissected to differentiate between, three different parts of
      the parametrium: the lateral parametrium, the proximal and the distal part of the
      posterior parametrium. Histologic and immunofluorescence analyses of nerve and
      lymphatic structures were performed using NSE and LYVE-1 staining, respectively.
      The percentage of structures was independently scored as 0 (0%), 1 (1-20%), 2 (20
      50%), 3 (50-80%), 4 (>80%). RESULTS: The lateral parametrium and the proximal
      part of the posterior parametrium contained both nerve (scored 2.25 and 2.50,
      respectively) and lymphatic (scored 2.50 and 2.00, respectively) structures. The
      distal part of the posterior parametrium also contained numerous nerve structures
      (scored 2.00) but lymphatic structures were rare (scored 0.88). No difference in
      nerve distribution was found according to the parts of parametrium while a
      significantly lower distribution of lymphatic vessels was observed in the distal
      part of the posterior parametrium (p=0.03). CONCLUSION: The distal part of the
      posterior parametrium is of high nerve density and low lymphatic density raising
      the issue as to whether it should be removed during radical hysterectomy.

PMID- 24125752
TI  - Impact of age-adjusted Charlson comorbidity score on outcomes for patients with
      early-stage endometrial cancer.
AB  - OBJECTIVES: To determine the impact of Age-Adjusted Charlson Comorbidity (AAC)
      index score on survival outcomes for patients with early stage endometrial
      cancer. METHODS: After IRB-approval, AAC score at time of hysterectomy was
      retrospectively tabulated by physician chart review for 671 patients with 2009
      FIGO stage I-II endometrioid adenocarcinoma. Patients were grouped based on their
      AAC scores as follows: 0-1 (n=204), 2-3 (n=293) and >3 (n=174). Kaplan-Meier and
      log-rank test methods and univariate and multivariate modeling with Cox
      regression analysis was used to determine significant predictors of each survival
      endpoint. RESULTS: After a median follow-up of 85 months, 225 deaths were
      recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and
      Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC
      grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%,
      96.8%, and 94.9% for AAC 0-1; 81.7%, 95.3%, and 89.8% for AAC 2-3: and 56%,
      88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On
      multivariate analyses, higher AAC score, tumor grade, lower uterine segment
      involvement, and lymphovascular space invasion were significantly independent
      predictors for shorter OS, while for DSS and RFS, higher tumor grade and
      lymphovascular space invasion were significant predictors of worse outcome, but
      higher AAC score was not. CONCLUSIONS: Comorbidity score is as important as
      pathological features for predicting overall survival outcomes in patients with
      early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately
      predicted for worse OS. Comorbidity score should be considered in prospective
      clinical trials of endometrial carcinoma.

PMID- 24125753
TI  - Self-collecting a cervico-vaginal specimen for cervical cancer screening: an
      exploratory study of acceptability among medically underserved women in rural
      Appalachia.
AB  - OBJECTIVE: Innovative screening methods such as self-testing for human
      papillomavirus (HPV) may alleviate barriers to cervical cancer screening. The
      purpose of this exploratory study was to determine whether Appalachian Kentucky
      women would be amenable to self-collecting a cervico-vaginal specimen for HPV
      testing. METHODS: Women aged 30-64 who were overdue for guideline-recommended
      cervical cancer screening were recruited from a primary care clinic in
      southeastern Kentucky. The women were asked to self-collect a specimen, using a
      cervico-vaginal brush, based on verbal and printed directions provided by a
      research nurse. All study participants, regardless of laboratory-confirmed HPV
      status, received the same counseling on the importance of cervical cancer
      screening and offered navigation to follow-up Pap testing at the local health
      department. RESULTS: Thirty-one women were approached and recruited to
      participate in the study, indicating a 100% acceptance rate of HPV self-testing.
      Of the 31 women, 26 tested negative for high-risk HPV and five tested positive.
      All of the women with negative results declined nurse navigation to Pap testing,
      whereas four of the five women with positive results accepted nurse navigation
      and received subsequent Pap smear screenings (all results were normal).
      CONCLUSIONS: Among this sample of Appalachian Kentucky women, self-collecting a
      cervico-vaginal specimen for HPV testing was highly acceptable. This exploratory
      study provides impetus for larger studies among high-risk, medically underserved
      women in rural communities. Tailoring alternative cancer screening strategies to
      meet the complex needs of rural women is likely to lead to reductions in cervical
      cancer incidence and mortality among this vulnerable population.

PMID- 24125754
TI  - Expression, purification, and characterization of formaldehyde dehydrogenase from
      Pseudomonas aeruginosa.
AB  - As a member of zinc-containing medium-chain alcohol dehydrogenase family,
      formaldehyde dehydrogenase (FDH) can oxidize toxic formaldehyde to less active
      formate with NAD(+) as a cofactor and exists in both prokaryotes and eukaryotes.
      Most FDHs are well known to be glutathione-dependent in the catalysis of
      formaldehyde oxidation, but the enzyme from Pseudomonas putida is an exception,
      which is independent of glutathione. To identify novel glutathione-independent
      FDHs from other bacterial strains and facilitate the corresponding structural and
      enzymatic studies, high-level soluble expression and efficient purification of
      these enzymes need to be achieved. Here, we present molecular cloning,
      expression, and purification of the FDH from Pseudomonas aeruginosa, which is a
      Gram-negative pathogenic bacterium causing opportunistic human infection. The FDH
      of P. aeruginosa shows high sequence identity (87.97%) with that of P. putida.
      Our results indicated that coexpression with molecular chaperones GroES, GroEL,
      and Tig has significantly attenuated inclusion body formation and improved the
      solubility of the recombinant FDH in Escherichiacoli cells. A purification
      protocol including three chromatographic steps was also established to isolate
      the recombinant FDH to homogeneity with a yield of ~3.2 mg from 1L of cell
      culture. The recombinant P. aeruginosa FDH was properly folded and biologically
      functional, as demonstrated by the mass spectrometric, crystallographic, and
      enzymatic characterizations of the purified proteins.

PMID- 24125755
TI  - FGF2 stimulates osteogenic differentiation through ERK induced TAZ expression.
AB  - TAZ (transcriptional coactivator with PDZ-binding motif) is a transcriptional
      modulator that regulates mesenchymal stem cell differentiation. It stimulates
      osteogenic differentiation while inhibiting adipocyte differentiation. FGFs
      (fibroblast growth factors) stimulate several signaling proteins to regulate
      their target genes, which are involved in cell proliferation, differentiation,
      and cell survival. Within this family, FGF2 stimulates osteoblast differentiation
      though a mechanism that is largely unknown. In this report, we show that TAZ
      mediates FGF2 signaling in osteogenesis. We observed that FGF2 increases TAZ
      expression by stimulating its mRNA expression. Depletion of TAZ using small
      hairpin RNA blocked FGF2-mediated osteogenic differentiation. FGF2 induced TAZ
      expression was stimulated by ERK (extracellular signal-regulated kinase)
      activation and the inhibition of ERK blocked TAZ expression. FGF2 increased
      nuclear localization of TAZ and, thus, facilitated the interaction of TAZ and
      Runx2, activating Runx2-mediated gene transcription. Taken together, these
      results suggest that TAZ is an important mediator of FGF2 signaling in osteoblast
      differentiation. 

PMID- 24125757
TI  - Target-induced electronic switch for ultrasensitive detection of Pb2+ based on
      three dimensionally ordered macroporous Au-Pd bimetallic electrode.
AB  - A novel strategy for selective and sensitive amperometric detections of Pb(2+)
      was proposed based on the three dimensional ordered macroporous (3DOM) Au-Pd
      bimetallic electrode and target-induced methylene blue-single walled carbon
      nanotubes (MB-SWCNTs) as signal reporter. A DNA biosensor was fabricated by
      immobilizing capture probe DNA on the 3DOM Au-Pd bimetallic electrode, which
      further hybridized with the reporter DNA loaded on the MB-SWCNTs adduct upon the
      exposure of Pb(2+), inducing measurable electrochemical signal. Due to the
      dramatic signal amplification by the enhanced immobilization of DNA on the
      surface of 3DOM Au-Pd bimetallic electrode and MB-SWCNTs, coupling the low
      background signal produced by blank solution, ultra-low level (1 * 10(-19)M) of
      Pb(2+) could be detected. Under the optimal conditions, the electrochemical
      signal of the MB increased with the increasing Pb(2+) concentration, exhibiting a
      linear response in the range of 1 * 10(-17)-1 * 10(-4)M. Furthermore, with the
      application of Pb(2+) dependent DNAzyme, the proposed sensing system demonstrated
      high selectivity. This work represented a promising potential for on-site testing
      Pb(2+) in real drinking water and serum sample analysis.

PMID- 24125756
TI  - A comparative study of the bone metabolic response to dried plum supplementation
      and PTH treatment in adult, osteopenic ovariectomized rat.
AB  - Dried plum has been reported to have potent effects on bone in osteopenic animal
      models, but the mechanisms through which bone metabolism is altered in vivo
      remain unclear. To address this issue, a study comparing the metabolic response
      of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken.
      Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or
      ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia
      was confirmed. Treatments were initiated consisting of a control diet (AIN-93M)
      supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group
      receiving PTH. At the end of 6wks of treatment, whole body and femoral bone
      mineral density (BMD) were restored by the two higher doses of dried plum to the
      level of the SHAM group. Trabecular bone volume and cortical thickness were also
      improved with these two doses of dried plum. Dried plum suppressed the OVX
      induced increase in bone turnover as indicated by systemic biomarkers of bone
      metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD).
      Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that
      dried plum restored the OVX-induced increase in cancellous bone formation rate
      (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried
      plum increased endocortical mineral apposition rate (MAR). As expected, PTH
      significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular
      MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone
      resorption associated with OVX. Dried plum up-regulated bone morphogenetic
      protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating
      nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in
      the adult osteopenic OVX animal, the effects of dried plum differ from that of
      PTH in that dried plum primarily suppressed bone turnover with the exception of
      the indices of bone formation at the endocortical surface. 

PMID- 24125758
TI  - In vivo evaluation of a chip based near infrared sensor for continuous glucose
      monitoring.
AB  - In this paper we describe the concept and in vivo results of a minimally
      invasive, chip-based near infrared (NIR) sensor, combined with microdialysis, for
      continuous glucose monitoring. The sensor principle is based on difference
      absorption spectroscopy in selected wavelength bands of the near infrared
      spectrum (1300 nm, 1450 nm, and 1550 nm) in the 1st overtone band. In vitro
      measurements revealed a linear relationship between glucose concentration and the
      integrated difference spectroscopy signal with a coefficient of determination of
      99% in the concentration range of 0-400mg/dl. The absolute error in this case is
      about 5mg/dl, corresponding to a relative error of about 5% for glucose
      concentrations larger than 50mg/dl and about 12% in the hypoglycemic range
      (<50mg/dl). In vivo measurements on 10 patients showed that the NIR-CGM sensor
      data reflects the blood reference values adequately, if a proper calibration and
      a signal drift correction is applied. The mean MARE (mean absolute relative
      error) value taken over all patient data is 13.8%. The best achieved MARE value
      is at 4.8%, whereas the worst lies at 25.8%, leading to a standard deviation of
      5.5%.

PMID- 24125759
TI  - Detection of methicillin-resistant Staphylococcus aureus using a gold
      nanoparticle-based colourimetric polymerase chain reaction assay.
AB  - We report the use of gold nanoparticles (Au NPs) for direct colourimetric
      polymerase chain reaction (PCR) detection of methicillin-resistant Staphylococcus
      aureus (MRSA) in clinical specimens. The colourimetric assay comprised of 2 Au NP
      probes functionalized with Staphylococcus aureus 23S rRNA- and mecA-specific
      oligonucleotides. In this study, 72 clinical samples were tested, which included
      positive blood culture (n=23), urine (n=8), respiratory samples (n=23), as well
      as wound swabs, pus and body fluid (n=18). Results were recorded qualitatively by
      direct visual examination and quantitatively by UV-vis spectrophotometry. Using
      conventional bacterial culture as the gold standard, the sensitivity,
      specificity, positive predictive value and negative predictive value of this
      colourimetric assay were 97.14%, 91.89%, 91.89% and 97.14%, respectively, which
      were comparable to that of commercial real-time PCR assays with a lower cost per
      reaction. Our assay also showed good agreement with bacterial culture
      (kappa=0.889). The overall detection limit was 500 ng target amplicon, which was
      comparable to or better than other similar Au NP biosensors. Interestingly, our
      data revealed the possible relationship between Au NP probe-target hybridization
      site and assay performance, which might provide hints for design of the Au NP
      biosensors for nucleic acid detection. To conclude, our study was the first
      report on the use of Au NP colourimetric assay for direct detection of MRSA in
      various types of clinical specimens. Further evaluation of the assay is needed in
      large-scale trials which can also allow for some modifications to streamline the
      procedures for routine use.

PMID- 24125760
TI  - Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3-5
      chronic kidney disease patients.
AB  - AIM: To determine the associations between insulin resistance, fibroblast growth
      factor 23 (FGF-23), and coronary artery calcification (CAC) in chronic kidney
      disease (CKD) patients. INTRODUCTION: FGF-23 is associated with atherosclerosis
      and cardiovascular disease, but its association with insulin resistance in CKD
      has not been explored. SUBJECTS: Cross sectional study of 72 stage 3-5 CKD
      patients receiving care in Ontario, Canada. MATERIALS AND METHODS: Insulin
      resistance was measured by the homeostasis model assessment of insulin resistance
      (HOMA-IR), FGF-23 was measured by carboxyl terminal enzyme linked immunoassay
      (ctFGF-23) and CAC was measured by multi-slice computed tomography. RESULTS:
      Median HOMA-IR was 2.19MUU/ml (interquartile range 1.19 to 3.94). Patients with
      HOMA-IR>2.2 had greater ctFGF-23 (179.7 vs 109.6; P=0.03), and 40% higher log CAC
      scores (2.09+/-0.87 vs 1.58+/-1.26; P=0.049). Multivariable linear regression
      adjusted for 1,25 dihydroxyvitamin D, kidney function, and parathyroid hormone
      revealed insulin resistance was a risk factor for greater log ctFGF-23 levels
      (log HOMA IR beta=0.37; 95% confidence interval 0.14 to 0.59; P=0.002).
      CONCLUSIONS: Insulin resistant CKD patients demonstrated higher FGF-23 levels,
      and increased CAC, while PO4 levels remained normal, suggesting a potential link
      between insulin resistance and PO4 homeostasis in CKD.

PMID- 24125761
TI  - N-Glycosylation during translation is essential for human arylacetamide
      deacetylase enzyme activity.
AB  - Human arylacetamide deacetylase (AADAC) can hydrolyze clinical drugs such as
      flutamide, phenacetin, and rifamycins. AADAC is a glycoprotein, but the role of
      glycosylation remains unclear. In the present study, we investigated the effect
      of glycosylation on AADAC enzyme activity. Immunoblot analysis of mutant AADACs
      that contained an asparagine (N, Asn) to glutamine (Q, Gln) substitution at
      either residue 78 or 282 (N78Q or N282Q) showed a different migration compared
      with the wild-type protein. A mutant AADAC that contained N to Q substitutions at
      both residue 78 and 282 (N78Q/N282Q) showed a similar migration to AADAC in human
      liver microsomes (HLM) treated with endoglycosidase H (Endo H), which produces
      deglycosylated proteins. This result indicated that AADAC was glycosylated at
      both N78 and N282. Mutant types of AADAC with the N282Q and the N78Q/N282Q
      substitutions showed dramatically lower phenacetin hydrolase activity than did
      the wild-type protein. The treatment of wild-type AADAC-expressing HuH-7 cells
      with tunicamycin, which produces unglycosylated protein, decreased AADAC enzyme
      activity. However, the treatment of the HLM with Endo H caused no decrease of
      AADAC activity. Thus, the oligosaccharide chain, per se, was not important for
      AADAC activity in the mature form. The mutant types of AADAC containing the N282Q
      and the N78Q/N282Q substitutions were not detected by immunoblotting analysis
      after non-reducing SDS-PAGE, suggesting that the glycosylation of AADAC at N282
      was important for proper protein folding. Overall, this study found that the
      translational, but not post-translational, N-glycosylation of AADAC plays a
      crucial role in regulating AADAC enzyme activity. 

PMID- 24125762
TI  - "I am not a skinny toothpick and proud of it": Latina adolescents' ethnic
      identity and responses to mainstream media images.
AB  - Using a quasi-experimental design, 118 Latina girls, ages 13-18, viewed five
      color photographs of White women. Girls viewed either images of sexualized women
      or images of non-sexualized women. After viewing the images, girls were asked to
      complete the sentence stem, "I am..." 20 times. Thirty percent of girls
      spontaneously described their ethnicity in one of their sentence completions.
      Spontaneous use of ethnicity was taken as an indicator of the salience of ethnic
      identity. Among girls who viewed sexualized, thin-ideal White media images,
      spontaneously using an ethnic descriptor was related to more positive
      descriptions of one's own body and appearance. Analyses supported the premise
      that ethnic identity may act as a protective factor, buffering Latina girls from
      the negative effects of viewing sexualized, thin-ideal White media images. 

PMID- 24125763
TI  - Immunological targeting of tumor cells undergoing an epithelial-mesenchymal
      transition via a recombinant brachyury-yeast vaccine.
AB  - The embryonic T-box transcription factor brachyury is aberrantly expressed in a
      range of human tumors. Previous studies have demonstrated that brachyury is a
      driver of the epithelial-mesenchymal transition (EMT), a process associated with
      cancer progression. Brachyury expression in human tumor cells enhances tumor
      invasiveness in vitro and metastasis in vivo, and induces resistance to various
      conventional therapeutics including chemotherapy and radiation. These
      characteristics, and the selective expression of brachyury for a range of human
      tumor types vs. normal adult tissues, make brachyury an attractive tumor target.
      Due to its intracellular localization and the "undruggable" character of
      transcription factors, available options to target brachyury are currently
      limited. Here we report on the development and characterization of an
      immunological platform for the efficient targeting of brachyury-positive tumors
      consisting of a heat-killed, recombinant Saccharomyces cerevisiae (yeast)
      brachyury vector-based vaccine (designated as GI-6301) that expresses the full
      length human brachyury protein. We demonstrate that human dendritic cells treated
      with recombinant yeast-brachyury can activate and expand brachyury-specific CD4+
      and CD8+ T cells in vitro that, in turn, can effectively lyse human tumor cells
      expressing the brachyury protein. Vaccination of mice with recombinant yeast
      brachyury is also shown here to elicit brachyury-specific CD4+ and CD8+ T-cell
      responses, and to induce anti-tumor immunity in the absence of toxicity. Based on
      these results, a Phase I clinical trial of GI-6301 is currently ongoing in
      patients with advanced tumors; to our knowledge, this is the first vaccine
      platform aimed at targeting a driver of tumor EMT that has successfully reached
      the clinical stage. 

PMID- 24125764
TI  - Genetic dissection of complete genomes of Type 2 PRRS viruses isolated in Denmark
      over a period of 15 years.
AB  - Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) was first
      detected in Europe in 1996 co-incident with the introduction of a live attenuated
      vaccine. Since then, only limited ORF5 and ORF7 sequences of Type 2 PRRS viruses
      have been reported throughout Europe. In the present study, the genetic and
      antigenic diversity of 11 complete genomes and 49 ORF5 and 55 ORF7 nucleotide
      sequences obtained from 57 viruses in Denmark from 2003 to 2012 were examined.
      The genetic identity of the 11 complete genomes to the vaccine strain (Ingelvac
      PRRS MLV) ranged between 93.6 and 99.6% while the 49 ORF5 sequences examined were
      94.0-99.8% identical to the vaccine strain. Among the Danish sequences, the
      pairwise nucleotide identity was 90.9-100% and 93.0-100.0% for ORF5 and ORF7,
      respectively. Analysis of the genetic region encoding NSP2 revealed high
      diversity among the Danish viruses with an 86.6-98.9% range in similarity.
      Furthermore, several of the sequenced viruses harbored deletions in the NSP2
      coding region. Phylogenetic analysis in a global Type 2 PRRSV framework
      classified all Danish isolates to a single cluster (sub-lineage 5.1) which
      comprised strains closely-related to the Type 2 prototype isolate VR2332. 

PMID- 24125765
TI  - [Serum total cholesterol levels and eligibility for long-term care insurance: a
      prospective cohort study of the Tsurugaya project].
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      serum total cholesterol levels and certification eligibility for long-term care
      insurance in elderly Japanese individuals. METHODS: The Tsurugaya Project was a
      comprehensive geriatric assessment conducted for community-dwelling elderly
      individuals aged >=70 years in the Tsurugaya area, Sendai, Japan. Of the 2,925
      inhabitants, 958 subjects participated in the Tsurugaya Project. For this
      analysis, we used 827 subjects who gave informed consent and were not qualified
      for long-term care insurance at the time of the baseline survey. Subjects were
      followed up for 6 years. We classified the subjects into 4 quintiles and used the
      fourth quintile (212-230 mg/dL) as a reference for statistical analysis. We used
      Cox proportional hazards model to estimate the hazard ratios (HRs) and 95%
      confidence intervals (CIs) of certification eligibility for long-term care
      insurance according to total cholesterol levels in serum. RESULTS: During 6 years
      of follow-up, a total of 214 subjects were qualified for long-term care insurance
      certification. The lowest serum total cholesterol level (<177 mg/dL) was
      significantly associated with increased eligibility for long-term care insurance
      certification. Compared with the fourth quintile, multivariate HRs (95%CIs) of
      long-term care insurance certification were 1.91 (1.23-2.98), 1.36 (0.85-2.18),
      0.99 (0.62-1.56), 1.38 (0.88-2.17), for <177 mg/dL, 177-194 mg/dL, 195-211 mg/dL,
      and <=231 mg/dL, respectively. Moreover, the association was statistically
      significant even after excluding subjects with a history of liver disease or
      cancer, an abnormality in the liver function test, or high levels of high
      sensitivity C-reactive protein. CONCLUSION: Low serum total cholesterol levels
      were significantly associated with increased eligibility for long-term care
      insurance certification even after adjusting for a variety of confounding
      factors.

PMID- 24125766
TI  - [Prevalence of smoking experience, second-hand smoke, recognition of smoking, and
      effect of anti-smoking education among 7,585 children of 153 elementary schools
      in Saga Prefecture].

PMID- 24125767
TI  - [A cross-sectional study of renal function based on estimated glomerular
      filtration rate and urinary protein levels related to risk factors for
      cardiovascular events and metabolic syndrome in local residents].
AB  - OBJECTIVES: In a cross-sectional study, we investigated renal function based on
      estimated glomerular filtration rate (eGFR) and urinary protein levels from
      Specific Health Examinations in Kitakyushu city related to risk factors for
      cardiovascular events and metabolic syndrome in residents. METHODS:  For this
      study, 21,625 citizens (male/female=8,637/12,988) of Kitakyushu city were
      investigated. Citizens were enrolled in national health insurance and data were
      collected from a database classified for "Specific Health Guidance" by the Kokura
      Medical Association health testing and services center in 2010. RESULTS: As a
      whole, the stage of CKD increased with age, especially among those aged 70-74
      years; 32% were at CKD stage 3. Only 11% of the CKD stage 3 group had a positive
      urinary protein (UP) test. Subjects in stages 3-5 CKD had a higher ratio of
      abdominal obesity, higher systolic and diastolic blood pressure, increased
      fasting blood glucose, HbA1c, and fasting triglyceride levels, and lower levels
      of HDL-C in comparison to subjects with CKD in stages 1-2. These factors increase
      the complication ratio of MetS for subjects in stages 3-5. The group with a
      history of stroke or heart disease had a significantly lower eGFR. CONCLUSION:
      There is a strong relationship between CKD and risk factors for cardiovascular
      events and MetS. It has been indicated that lifestyle modifications, suggested by
      primary care doctors, are very important for the early prevention of CKD. A new
      preventive CKD system in Kitakyushu city, based on a Specific Health Examination,
      began during the fiscal year 2011, and this system is expected to decrease the
      incidence of end-stage renal disease and cardiovascular events.

PMID- 24125768
TI  - [The current state of pediatric palliative care in England: policy and law,
      statistics, funding and service provisions].

PMID- 24125769
TI  - Sublingual microcirculation in patients with intra-abdominal hypertension: a
      pilot study in 15 critically ill patients.
AB  - PURPOSE: The purpose of the study is to clarify whether increased intra-abdominal
      pressure (IAP) is associated with sublingual microcirculatory alterations in
      intensive care patients. METHODS: Fifteen adult, mechanically ventilated patients
      were included if their IAP was at least 12 mm Hg for at least 12 hours within the
      first 3 days after admission to the intensive care unit. Sublingual sidestream
      dark field (SDF) images were recorded twice a day for 7 days. RESULTS: Median
      (interquartile range) IAP at inclusion was 14.5 (12.5-16.0) mm Hg. The total
      vascular density of small vessels at the sublingual area was 13.1 (10.6-14.3) per
      square millimeter at baseline; the proportion of perfused vessels, 78.9% (69.6%
      86.2%); and perfused vessels density, 12.4 (10.8-13.8) per square millimeter. The
      calculated indices suggested relatively good blood flow in the capillaries, with
      a De Backer score of 9.0 (8.3-10.2) and a microvascular blood flow of 3.0 (2.9
      3.0). Blood flow heterogeneity index was 0.3 (0.1-0.5) at study entry. Despite
      that IAP, vasopressors dose, and arterial lactate decreased significantly over
      time, no significant changes were observed in sublingual microvascular density or
      blood flow. Weak correlations of microvascular blood flow (positive) and
      heterogeneity index (negative) were detected with both mean arterial pressure and
      abdominal perfusion pressure. CONCLUSIONS: Neither grade I or II intra-abdominal
      hypertension (IAP from 12 to 18 mm Hg) is associated with significant changes of
      sublingual microcirculation in intensive care patients. Correlation analysis
      indicates better microvascular blood flow at higher mean arterial pressure and
      abdominal perfusion pressure levels.

PMID- 24125770
TI  - Predictors of extraventricular drain-associated bacterial ventriculitis.
AB  - PURPOSE: Bacterial ventriculitis (BV) may develop in patients requiring external
      ventricular drains (EVDs). The purpose of this study was to determine predictors
      of EVD-associated BV onset. MATERIALS AND METHODS: A retrospective review of Duke
      University Hospital patients with EVD device placement between January 2005 and
      May 2010 was conducted. Subject data were captured for predefined variables.
      Outcomes included in-hospital mortality, length of stay, and neurologic status at
      discharge. RESULTS: In 410 subjects with 420 EVDs, the BV rate was 10.2%.
      Univariate analysis indicated that age, sex, positive blood culture, duration of
      EVD placement, and the number of cerebrospinal fluid (CSF) samples taken were
      associated with BV. Of these, the number of CSF samples and sex retained
      significance in multivariable modeling (female: odds ratio, 0.47 [confidence
      interval, 0.23-0.97]; CSF samples: odds ratio, 1.08 [confidence interval 1.01
      1.17]; P = .04; c index = 0.69). In this model, each CSF sample taken expanded
      the likelihood of BV by 8.3%. The most common pathogens were Staphylococcus or
      proprioniobacter (n = 26). Bacterial ventriculitis was associated with an
      increase in hospital length of stay (33 +/- 22.9 days vs 24.6 +/- 20.4 days; P =
      .04) but not mortality. CONCLUSION: An association exists between CSF sampling
      frequency and the development of EVD-associated BV. Larger prospective studies
      should be aimed at identifying causal relationships between these variables.

PMID- 24125771
TI  - Auditory-evoked potentials during coma: do they improve our prediction of
      awakening in comatose patients?
AB  - OBJECTIVE: The mismatch negativity (MMN), an auditory event-related potential,
      has been identified as a good indicator of recovery of consciousness during coma.
      We explored the predictive value of the MMN and other auditory-evoked potentials
      including brainstem and middle-latency potentials for predicting awakening in
      comatose patients after cardiac arrest or cardiogenic shock. MATERIALS AND
      METHODS: Auditory brainstem, middle-latency (Pa wave), and event-related
      potentials (N100 and MMN waves) were recorded in 17 comatose patients and 9
      surgical patients matched by age and coronary artery disease. Comatose patients
      were followed up daily to determine recovery of consciousness and classified as
      awakened and nonawakened. RESULTS: Among the auditory-evoked potentials, the
      presence or absence of MMN best discriminated between patients who awakened or
      those who did not. Mismatch negativity was present during coma in all patients
      who awakened (7/7) and in 2 of those (2/10) who did not awaken. In patients who
      awakened and in whom MMN was detected, 3 of those awakened between 2 and 3 days
      and 4 between 9 and 21 days after evoked potential examination. All awakened
      patients had intact N100 waves and identifiable brainstem and middle-latency
      waves. In nonawakened patients, N100 and Pa waves were detected in 5 cases (50%)
      and brainstem waves in 9 (90%). CONCLUSIONS: The MMN is a good predictor of
      awakening in comatose patients after cardiac arrest and cardiogenic shock and can
      be measured days before awakening encouraging ongoing life support.

PMID- 24125772
TI  - Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co
      poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment.
AB  - Based on the facilitative glucose transporter (GLUT) over-expression on both
      blood-brain barrier (BBB) and glioma cells, 2-deoxy-d-glucose modified
      poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (dGlu-NP)
      were developed as a potential dual-targeted drug delivery system for enhancing
      the BBB penetration via GLUT-mediated transcytosis and improving the drug
      accumulation in the glioma via GLUT-mediated endocytosis. In vitro
      physicochemical characterization of the dual-targeted nanoparticulate system
      presented satisfactory size of 71 nm with uniform distribution, high
      encapsulation efficiency and adequate loading capacity of paclitaxel (PTX).
      Compared with non-glucosylated nanoparticles (NP), a significantly higher amount
      of dGlu-NP was internalized by RG-2 glioma cells through caveolae-mediated and
      clathrin-mediated endocytosis. Both of the transport ratios across the in vitro
      BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were
      significantly greater of dGlu-NP/PTX than that of NP/PTX. In vivo fluorescent
      image indicated that dGlu-NP had high specificity and efficiency in intracranial
      tumor accumulation. The anti-glioblastoma efficacy of dGlu-NP/PTX was
      significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary
      safety tests showed no acute toxicity to hematological system, liver, kidney,
      heart, lung and spleen in mice after intravenous administration at a dose of 100
      mg/kg blank dGlu-NP per day for a week. Therefore, these results indicated that
      dGlu-NP developed in this study could be a potential dual-targeted vehicle for
      brain glioma therapy.

PMID- 24125773
TI  - TGF-beta3-induced chondrogenesis in co-cultures of chondrocytes and mesenchymal
      stem cells on biodegradable scaffolds.
AB  - In this work, it was hypothesized that co-cultures of articular chondrocytes
      (ACs) and mesenchymal stem cells (MSCs) would exhibit enhanced sensitivity to
      chondrogenic stimuli, such as TGF-beta3, and would require a reduced
      concentration of TGF-beta3 to achieve an equivalent level of chondrogenesis
      compared to monocultures of each cell type. Furthermore, it was hypothesized that
      compared to monocultures, the chondrogenic phenotype of AC/MSC co-cultures would
      be more stable upon the removal of TGF-beta3 from the culture medium. These
      hypotheses were investigated by culturing ACs and MSCs alone and in a 1:3 ratio
      on electrospun poly(epsilon-caprolactone) scaffolds. All cell populations were
      cultured for two weeks with 0, 1, 3, or 10 ng/ml of TGF-beta3. After two weeks
      growth factor supplementation was removed, and the constructs were cultured for
      two additional weeks. Cell proliferation, extracellular matrix production, and
      chondrogenic gene expression were evaluated after two and four weeks. The results
      demonstrated that co-cultures of ACs and MSCs require a reduced concentration and
      duration of TGF-beta3 exposure to achieve an equivalent level of chondrogenesis
      compared to AC or MSC monocultures. Thus, the present work implicates that the
      promise of co-cultures for cartilage engineering is enhanced by their robust
      phenotype and heightened sensitivity to TGF-beta3.

PMID- 24125774
TI  - Enhancement of bone regeneration by dual release of a macrophage recruitment
      agent and platelet-rich plasma from gelatin hydrogels.
AB  - Macrophages play an important role in regulating inflammatory responses and
      tissue regeneration. In the present study, their effect on bone remodeling is
      investigated by the simultaneous application of a macrophage recruiting agent,
      SEW2871 of a sphingosine-1 phosphate agonist, and platelet-rich plasma (PRP). The
      non-water soluble SEW2871 was solubilized in water through micelles formation
      with l-lactic acid grafted gelatin, and the resulting micelles with PRP were
      incorporated into gelatin hydrogels. Mixed SEW2871-micelles and PRP were released
      from gelatin hydrogels in a controlled fashion both in vitro and in vivo. In
      vitro migration assay revealed that the presence of PRP synergistically promoted
      SEW2871-induced macrophages migration. When applied to a bone defect of rats, the
      hydrogels incorporating mixed SEW2871-micelles and PRP recruited a higher number
      of macrophages than those hydrogels incorporating either SEW2871-micelles or PRP.
      The hydrogels incorporating mixed SEW2871-micelles and PRP enhanced the level of
      tumor necrosis factor (TNF)-alpha of pro-inflammatory cytokine, 3 days after
      application, while pro-inflammatory responses coupled with a significant increase
      in the expression level of osteoprotegerin (OPG) and interleukin (IL)-10 and
      transforming growth factor (TGF)-beta1 of anti-inflammatory cytokine were
      observed 10 days postoperatively. The hydrogels incorporating mixed SEW2871
      micelles and PRP promoted bone regeneration to a significant great extent
      compared with those incorporating PBS and either SEW2871-micelles or PRP. It is
      concluded that macrophages recruitment contributed to PRP-induced bone
      regeneration.

PMID- 24125775
TI  - Programmed nanoparticles for combined immunomodulation, antigen presentation and
      tracking of immunotherapeutic cells.
AB  - We report programmed nanoparticles (pNPs) that can tailor the immunotherapeutic
      function of primary bone marrow-derived dendritic cells (BMDCs) by ex vivo
      combined immunomodulation and track the in vivo migration of them after injection
      into body. Because DCs are the most effective antigen-presenting cells (APCs)
      that are able to present the antigens to T cells that contribute to tumor
      rejection, the maturation and monitoring of therapeutic DCs are essential for the
      efficient cancer immunotherapy. For combined immunomodulation of DCs, poly
      (lactic-co-glycolic acid) (PLGA) NPs containing both small interfering RNA
      (siRNA) for the knock-down of immune-suppressor gene (signal transducer and
      activator of transcription-3, STAT3) of DCs and an immune response modifier
      (imiquimod, R837) for the activation of DCs through the toll-like receptor 7
      (TLR7) were developed. To deliver tumor antigen-specific information to DCs ex
      vivo and track the migration of DCs in vivo, another type of PLGA NPs containing
      tumor model antigen (ovalbumin, OVA) and near-infrared (NIR) fluorophores
      (indocyanine green, ICG) were also fabricated. These pNPs were taken up
      efficiently by DCs and various cytokines were expressed in matured DCs. DCs
      treated with pNPs also efficiently presented antigen-peptide to CD8 OVA 1.3 T
      cells through cross-presentation. Immunization of mice with these pNPs-treated
      DCs induced OVA-specific cytotoxic T lymphocytes (CTL) activity against the EG7
      OVA tumor model and inhibited tumor growth efficiently. In addition, the
      migration of PLGA NPs-treated DCs to lymph nodes was monitored by NIR imaging
      technique. These multifunctional pNPs represent a promising technology for the
      combined immunomodulation and antigen-specific tumor therapy.

PMID- 24125776
TI  - The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and
      improve efficacy for non-small cell lung cancer therapy.
AB  - Bortezomib (BTZ) is the first clinically approved proteasome inhibitor for
      treating multiple human malignancies. However, the poor water-solubility and low
      stability of BTZ and the emergence of tumor resistance have severely restrained
      its therapeutic efficacy. Herein, we report the application of hollow mesoporous
      silica nanospheres (HMSNs) in encapsulating BTZ for drug delivery. In in vitro
      cell viability assay on human NSCLC H1299 cells, the half-maximum inhibiting
      concentration (IC50) of HMSNs-BTZ was 42% of that for free BTZ in 48 h
      treatments. In vivo tumor-suppression assay further indicated that HMSNs-BTZ (0.3
      mg/kg) showed approximately 1.5 folds stronger anti-tumor activity than free BTZ.
      Furthermore, we report that more potent induction of cell cycle arrest and
      apoptotic cell death, along with promoted activation of Caspase 3 and autophagy
      might mechanistically underlie the improved anti-tumor efficacy of HMSNs-BTZ.
      Finally, the tumor-suppressing effect of HMSNs-BTZ was enhanced in the presence
      of wild-type p53 signaling, suggesting a potential enhancement in clinical
      efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Therefore,
      the HMSNs-based nanoparticles are emerging as a promising platform to deliver
      therapeutic agents for beneficial clinical outcomes through lowering doses and
      frequency of drug administration and reducing potential side effects.

PMID- 24125778
TI  - Efficacy of bacteriophage LISTEXTMP100 combined with chemical antimicrobials in
      reducing Listeria monocytogenes in cooked turkey and roast beef.
AB  - The aim of this study was to verify the effectiveness of the commercially
      available anti-Listeria phage preparation LISTEX(TM)P100 in reducing Listeria
      monocytogenes on ready-to-eat (RTE) roast beef and cooked turkey in the presence
      or absence of the chemical antimicrobials potassium lactate (PL) and sodium
      diacetate (SD). Sliced RTE meat cores at 4 and 10  degrees C were inoculated with
      cold-adapted L. monocytogenes to result in a surface contamination level of
      10(3)CFU/cm(2). LISTEX(TM)P100 was applied at 10(7) PFU/cm(2) and samples taken
      at regular time intervals during the RTE product's shelf life to enumerate viable
      L. monocytogenes. LISTEX(TM)P100 was effective during incubation at 4  degrees C
      with initial reductions of L. monocytogenes of 2.1 log10 CFU/cm(2) and 1.7 log10
      CFU/cm(2), respectively, for cooked turkey and roast beef without chemical
      antimicrobials (there was no significant difference to the initial L.
      monocytogenes reductions in the presence of LISTEX(TM)P100 for cooked turkey
      containing PL and roast beef containing SD-PL). In the samples containing no
      chemical antimicrobials, the presence of phage resulted in lower L. monocytogenes
      numbers, relative to the untreated control, of about 2 log CFU/cm(2) over a 28
      day storage period at 4  degrees C. An initial L. monocytogenes cell reduction of
      1.5 log10 CFU/cm(2) and 1.7 log10 CFU/cm(2), respectively, for cooked turkey and
      roast beef containing no chemical antimicrobials was achieved by the phage at 10 
      degrees C (abusive temperature). At this temperature, the L. monocytogenes cell
      numbers of samples treated with LISTEXTM P100 remained below those of the
      untreated control only during the first 14 days of the experiment for roast beef
      samples with and without antimicrobials. On day 28, the L. monocytogenes numbers
      on samples containing chemical antimicrobials and treated with LISTEX(TM)P100
      stored at 4 and 10  degrees C were 4.5 log10 CFU/cm(2) and 7.5 log10 CFU/cm(2),
      respectively, for cooked turkey, and 1.2 log10 CFU/cm(2) and 7.2 log10 CFU/cm(2),
      respectively, for roast beef. In both cooked turkey samples with and without
      chemical antimicrobials stored at 10  degrees C, the phage-treated samples had
      significantly lower numbers of L. monocytogenes when compared to the untreated
      controls throughout the 28-day storage period (P<0.0001). For roast beef and
      cooked turkey containing chemical antimicrobials treated with LISTEX(TM)P100 and
      stored at 4  degrees C, no more than a 2 log CFU/cm(2) increase of L.
      monocytogenes was observed throughout the stated shelf life of the product. This
      study shows that LISTEX(TM)P100 causes an initial reduction of L. monocytogenes
      numbers and can serve as an additional hurdle to enhance the safety of RTE meats
      when used in combination with chemical antimicrobials.

PMID- 24125777
TI  - Murine xenogeneic models of myelodysplastic syndrome: an essential role for
      stroma cells.
AB  - The objective of is this article is to review murine xenotransplantation models
      for myelodysplastic syndromes (MDS). The difficulties in achieving sustained
      engraftment of MDS cells in immunodeficient mice may lie in innate
      characteristics of the MDS clones and microenvironmental factors. Engraftment of
      very low numbers of CD45(+) clonal MDS cells has been achieved with intravenous
      injection; higher rates of engraftment are obtained via the intramedullary route.
      Coinjection of certain stroma components with hematopoietic cells overcomes
      limitations of intravenous (IV) administration, allowing for engraftment of high
      proportions of human CD45(+) cells in mouse spleen and marrow. Expression of
      CD146 on stroma cells conveys an engraftment-facilitating effect. Clonal MDS
      cells have been propagated for periods beyond 6 months and have been transplanted
      successfully into secondary recipients. Engraftment of human clonal MDS cells
      with stem cell characteristics in immunodeficient mice is greatly facilitated by
      coinjection of stroma/mesenchymal cells, particularly with IV administration.
      CD146 expression on stroma is an essential factor; however, no model develops the
      laboratory and clinical features of human MDS. Additional work is needed to
      determine cellular and noncellular factors required for the full evolution of
      MDS. 

PMID- 24125779
TI  - [Cheek reconstruction].
AB  - We describe the different cheek reconstruction techniques with primary emphasis
      on the superficial layers. In addition to the clinical context, location and size
      of the lesion will be taken into account to choose the best method that will
      optimize the functional and aesthetic results while minimizing potential
      sequelae. Main evaluation criteria include absence of natural orifice
      deformation, scar location, skin cover quality and respect of volumes. 

PMID- 24125780
TI  - [Full thickness reconstruction of the nasal pyramid].
AB  - Nasal lesions, which are often carcinomas, require a histological control of the
      excision sometimes forcing to postpone the reconstruction source of nasal
      mutilation disfiguring. Reconstructive procedures have made steady progress and
      the notion of reconstruction in three planes advocated by Tiersch has been
      improved in a major way by Millard, Burget and Menick, who added an essential
      aesthetic dimension. We present our experience in this field by selecting
      procedures that seem most appropriate and describing the key points of the
      operating process, which remain the guarantee of both therapeutic and aesthetic
      success. 

PMID- 24125781
TI  - Antidepressant-like activity of resveratrol treatment in the forced swim test and
      tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation
      of ERK.
AB  - Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has
      diverse biological activities. There is only limited information about the
      antidepressant-like effect of resveratrol. The present study assessed whether
      resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant
      like effect on the forced swim test (FST) and tail suspension test (TST) in mice
      and examined what its molecular targets might be. The results showed that
      resveratrol administration produced antidepressant-like effects in mice,
      evidenced by the reduced immobility time in the FST and TST, while it had no
      effect on the locomotor activity in the open field test. Resveratrol treatment
      significantly reduced serum corticosterone levels, which had been elevated by the
      FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor
      (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation
      levels in the prefrontal cortex and hippocampus. All of these antidepressant-like
      effects of resveratrol were essentially similar to those observed with the
      clinical antidepressant, fluoxetine. These results suggest that the
      antidepressant-like effects of resveratrol in the FST and TST are mediated, at
      least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK
      phosphorylation expression in the brain region of mice. 

PMID- 24125782
TI  - Synergistic antinociception of propofol-alfentanil combination in mice.
AB  - Drug combination is frequently used in pain treatment, which can produce similar
      analgesia with reduced dosage and side effects. In the present study, we examined
      the effects of co-administration of propofol, a general anesthetic, and
      alfentanil, an opioid analgesic drug, and the types of interactions between them
      in heat induced acute phasic and acetic-acid induced acute tonic pain models
      using the up-and-down method. In both pain models, alfentanil was administered in
      fixed-dose fractions of the 50% effective dose (ED50), and the types of
      interactions were determined by isobolographic analysis. In hot plate test,
      alfentanil (35.6-50.0 MUg/kg, i.v.), propofol (6.5-15.5mg/kg, i.v.), and their
      combinations (80%, 50%, 30% and 10% of a single drug ED50) produce a significant,
      dose-dependent antinociception. In the tail-flick test, alfentanil (35.6-50.0
      MUg/kg, i.v.), propofol (5.0-14.3mg/kg, i.v.), and their combination
      significantly and dose dependently extend the tail-flick latency. In the acetic
      acid induced writhing test, alfentanil (12.5-23.2 MUg/kg, i.p.), propofol (15.0
      28.5mg/kg, i.p.), and their combination significantly and dose dependently reduce
      the frequency of writhing. In all the above pain models, isobolographic analysis
      revealed a significant synergistic interaction between alfentanil and propofol,
      with about 4-fold reduction of doses of both drugs, in comparison with each
      single drug's ED50. These data suggest that the combination of alfentanil and
      propofol synergistically suppresses acute phasic and tonic pain in mice,
      indicating a potential application in pain treatment.

PMID- 24125783
TI  - Chronic treatment with tandospirone, a 5-HT(1A) receptor partial agonist,
      suppresses footshock stress-induced lactate production in the prefrontal cortex
      of rats.
AB  - Serotonin 1A receptor (5-HT1A-R) agonists have been demonstrated to elicit
      antidepressant and anxiolytic effects. Lactate has been considered to play a
      major role in energy metabolism in the brain. Specifically, extracellular lactate
      concentrations (eLAC) have been suggested to reflect neural activity. Mild
      physical (e.g., handling) and non-physical (e.g., psychological) stressors have
      been shown to increase eLAC in several brain regions, including the medial
      prefrontal cortex (mPFC) and basolateral amygdala (BLA). Using in vivo
      microdialysis technique, we measured eLAC in the mPFC and BLA of rats under
      electric footshock stress to clarify the effect of repeated injection procedure
      (saline, once daily for 14 days) as a stressor on brain energy metabolism. Then,
      we examined the effect of chronic treatment with tandospirone, a 5-HT1A-R partial
      agonist, on eLAC during footshock stress in the mPFC. Footshock stress led to an
      increase in eLAC both in the mPFC and BLA in rats without injections. Repeated
      saline injection increased basal eLAC in the BLA, while footshock-induced lactate
      increment was reduced. In the mPFC, repeated saline injection did not affect
      basal eLAC and footshock-induced eLAC increments. Chronic treatment with
      tandospirone, at 0.2 and 1.0 mg/kg/day, but not 2.0 mg/kg/day, attenuated
      footshock stress-induced eLAC elevation in the mPFC. These observations suggest
      that eLAC in the BLA is sensitive to repeated exposure to physical stress. Data
      also indicate chronic treatment with tandospirone diminishes acute energy demands
      during neural activation in the mPFC. The implications of the present findings in
      relation to clinical efficacy of 5-HT1A agonists are discussed.

PMID- 24125784
TI  - Serotonin 1A, 1B, and 7 receptors of the rat medial nucleus accumbens
      differentially regulate feeding, water intake, and locomotor activity.
AB  - Serotonin (5-HT) signaling has been widely implicated in the regulation of
      feeding behaviors in both humans and animal models. Recently, we reported that co
      stimulation of 5-HT1&7 receptors of the anterior medial nucleus accumbens with
      the drug 5-CT caused a dose-dependent decrease in food intake, water intake, and
      locomotion in rats (Pratt et al., 2009). The current experiments sought to
      determine which of three serotonin receptor subtypes (5-HT1A, 5-HT1B, or 5-HT7)
      might be responsible for these consummatory and locomotor effects. Food-deprived
      rats were given 2-h access to rat chow after stimulation of nucleus accumbens 5
      HT1A, 5-HT1B, or 5-HT7 receptors, or blockade of the 5-HT1A or 5-HT1B receptors.
      Stimulation of 5-HT1A receptors with 8-OH-DPAT (at 0.0, 2.0, 4.0, and 8.0 MUg/0.5
      MUl/side) caused a dose-dependent decrease in food and water intake, and reduced
      rearing behavior but not ambulation. In contrast, rats that received the 5-HT1B
      agonist CP 93129 (at 0.0, 1.0, 2.0 and 4.0 MUg/0.5 MUl/side) showed a significant
      dose-dependent decrease in water intake only; stimulation of 5-HT7 receptors (AS
      19; at 0.0, 1.0, and 5.0 MUg/0.5 MUl/side) decreased ambulatory activity but did
      not affect food or water consumption. Blockade of 5-HT1A or 5-HT1B receptors had
      no lasting effects on measures of food consumption. These data suggest that the
      food intake, water intake, and locomotor effects seen after medial nucleus
      accumbens injections of 5-CT are due to actions on separate serotonin receptor
      subtypes, and contribute to growing evidence for selective roles of individual
      serotonin receptors within the nucleus accumbens on motivated behavior.

PMID- 24125785
TI  - Prefrontal hemodynamic changes during cigarette smoking in young adult smokers
      with and without ADHD.
AB  - Individuals with attention-deficit/hyperactivity disorder (ADHD) have elevated
      smoking prevalence and reduced cessation rates compared to the general
      population. However, the effects of cigarette smoking on underlying brain
      activity in smokers with ADHD are not well characterized. Non-invasive near
      infrared spectroscopy (NIRS) was used to characterize how cigarette smoking
      affects prefrontal brain hemodynamics in smokers with and without ADHD.
      Prefrontal changes of oxy- and deoxyhemoglobin (HbO2 and HHb) were measured in
      six male adult smokers with ADHD and six age- and gender-matched control smokers.
      NIRS measurements were separated into four sequential time intervals, i.e.,
      before smoking, during smoking, after smoking, and during a breath hold.
      Prefrontal HbO2 was lower during smoking in smokers with ADHD compared to control
      smokers. More specifically, smokers with ADHD showed decreased prefrontal HbO2
      during smoking compared to breath hold, before and after smoking periods. In
      contrast, control smokers showed increased prefrontal HbO2 from before smoking to
      breath hold. Decreased prefrontal HbO2 in smokers with ADHD may reflect a smoking
      induced change in prefrontal brain activity and microvasculature, which is not
      found in smokers without ADHD. The lower prefrontal HbO2 may be a biomarker for
      increased susceptibility to tobacco smoke in smokers with ADHD. Smoking in
      individuals with ADHD may increase vasoconstriction of cerebral arteries in the
      prefrontal cortex, which may contribute to a reduction in HbO2. The findings
      highlight the importance of smoking cessation, in particular in those smokers who
      use nicotine to self-medicate ADHD symptoms. 

PMID- 24125786
TI  - Animal models of female sexual dysfunction: basic considerations on drugs,
      arousal, motivation and behavior.
AB  - Female sexual dysfunctions are a heterogeneous group of symptoms with unknown but
      probably varying etiology. Social factors may contribute both to the prevalence
      and to the origin of these dysfunctions. The present review focuses on female
      hypoactive sexual desire disorder, sexual arousal disorder and orgasmic disorder.
      These disorders are generally the most common, according to epidemiological
      studies, and they can all be considered as disorders of motivation. An incentive
      motivational model of sexual behavior, applicable to humans as well as to non
      human animals, is described and the dysfunctions placed into the context of this
      model. It is shown that endocrine alterations as well as observable alterations
      in neurotransmitter activity are unlikely causes of the disorders. A potential
      role of learning is stressed. Nevertheless, the role of some transmitters in
      female rodent sexual behavior is analyzed, and compared to data from women,
      whenever such data are available. The conclusion is that there is no direct
      coincidence between effects on rodent copulatory behavior and sexual behavior in
      women. Based on these and other considerations, it is suggested that sexual
      approach behaviors rather than copulatory reflexes in rodents might be of some
      relevance for human sexual behavior, and perhaps even for predicting the effects
      of interventions, perhaps even the effects of drugs. Female copulatory behaviors,
      including the proceptive behaviors, are less appropriate. The common sexual
      dysfunctions in women are not problems with the performance of copulatory acts,
      but with the desire for such acts, by feeling aroused by such acts and
      experiencing the pleasure expected to be caused by such acts. Finally, it is
      questioned whether female sexual dysfunctions are appropriate targets for
      pharmacological treatment. 

PMID- 24125787
TI  - Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced
      antinociceptive effect in formalin test.
AB  - Orexin-A and orexin-B are two neuropeptides selectively synthesized in the
      lateral hypothalamus (LH), a region involved in morphine induced analgesia and
      pain modulation. Furthermore, orexin-A has been reported to produce an analgesic
      effect in pain models, which was blocked by orexin-1 receptor antagonist SB
      334867, but not naloxone. We studied the effects of intracerebroventricular (ICV)
      injection of SB-334867, a selective orexin receptor type-1 antagonist, on
      morphine-induced antinociceptive effect in formalin test in rats. Morphine
      injection at a dose of 1.5mg/kg caused a significant decrease in the formalin
      induced nociceptive behaviors in phase 1, interphase, and phase 2A, whereas at
      doses of 3, 6, and 10mg/kg, a significant reduction in the formalin-induced
      nociceptive behaviors was observed in all phases. The ICV injection of SB-334867
      alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment
      with SB-334867 at a dose of 0.5 nmol significantly attenuated the analgesia
      induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at
      dose 3mg/kg of morphine just phase 2B of formalin test). Also, pre-treatment with
      SB-334867 at a dose of 5 nmol considerably attenuated the morphine-induced
      analgesia (at dose 1.5mg/kg of morphine; phase 1, interphase, and phase 2, at
      dose 3 and 6 mg/kg of morphine just phase 2 of formalin test). Pre-treatment with
      SB-334867 at a dose of 50 nmol remarkably attenuated the morphine-induced
      analgesia (at dose 1.5 and 3mg/kg of morphine; in phase 1, interphase, and phase
      2 and also at dose 6 mg/kg of morphine; phase 1 and phase 2B of formalin test).
      These data suggest that the antinociceptive effects of morphine in formalin test
      might be associated with orexin receptor type-1. Our findings reveal a new role
      for the lateral hypothalamus orexin neurons in the morphine-induced analgesia.

PMID- 24125788
TI  - Benign infantile convulsions associated with mild gastroenteritis: an
      electroclinical study of 34 patients.
AB  - PURPOSE: To analyze the electroclinical features and evolution of patients
      diagnosed with convulsions with mild gastroenteritis (CwG) from southwest China.
      METHODS: We reviewed and analyzed the medical records of 34 patients (13 males)
      diagnosed with CwG and followed-up for at least 12 months. RESULTS: The age of
      onset was 6-29 months and the female/male ratio 1.62. Seizures were generalized
      in 32 cases. Single seizures in 15 cases were <5 min and multiple seizures 24-48
      h after seizure onset were seen in 18 cases. Seizure duration was <1 min in
      32.35%, between 1 and 5 min in 55.88%, and between 5 and 10 min in 8.82% of
      seizures. The average interval between the onset of gastroenteritis and seizures
      was 2.47 days. Rotavirus antigen was positive in stools in 26.47% of cases.
      During the acute phase, diazepam and phenobarbital as first-line treatment were
      effective in 25% and 83.33% of cases, respectively. Fourteen patients showed non
      specific anomalies in the interictal electroencephalography. During 12-36 months
      follow-up, 33 cases showed normal psychomotor development and no seizures.
      CONCLUSIONS: CwG occurred mostly in toddlers. During the acute phase,
      phenobarbital is more effective in controlling seizures. For a good prognosis, it
      is unnecessary to administrate long-term anticonvulsants.

PMID- 24125789
TI  - Validating a vignette-based instrument to study physician decision making in
      trauma triage.
AB  - BACKGROUND: The evidence supporting the use of vignettes to study physician
      decision making comes primarily from the study of low-risk decisions and the
      demonstration of good agreement at the group level between vignettes and actual
      practice. The validity of using vignettes to predict decision making in more
      complex, high-risk contexts and at the individual level remains unknown. METHODS:
      We had previously developed a vignette-based instrument to study physician
      decision making in trauma triage. Here, we measured the retest reliability,
      internal consistency, known-groups performance, and criterion validity of the
      instrument. Thirty-two emergency physicians, recruited at a national academic
      meeting, participated in reliability testing. Twenty-eight trauma surgeons,
      recruited using personal contacts, participated in known-groups testing. Twenty
      eight emergency physicians, recruited from physicians working at hospitals for
      which we had access to medical records, participated in criterion validity
      testing. We measured rates of undertriage (the proportion of severely injured
      patients not transferred to trauma centers) and overtriage (the proportion of
      patients transferred with minor injuries) on the instrument. For physicians
      participating in criterion validity testing, we compared rates of triage on the
      instrument with rates in practice, based on chart review. RESULTS: Physicians
      made similar transfer decisions for cases (kappa = 0.42, P < 0.01) on 2
      administrations of the instrument. Responses were internally consistent (Kuder
      Richardson, 0.71-0.91). Surgeons had lower rates of undertriage than emergency
      physicians (13% v. 70%, P < 0.01). No correlation existed between individual
      rates of under- or overtriage on the vignettes and in practice (r = -0.17, P =
      0.4; r = -0.03, P = 0.85). CONCLUSIONS: The instrument developed to assess trauma
      triage decision making performed reliably and detected known group differences.
      However, it did not predict individual physician performance.

PMID- 24125790
TI  - Better medicine by default.
AB  - BACKGROUND: American health care is transitioning to electronic physician
      ordering. These computerized systems are unique because they allow custom order
      interfaces. Although these systems provide great benefits, there are also
      potential pitfalls, as the behavioral sciences have shown that the very format of
      electronic interfaces can influence decision making. The current research
      specifically examines how defaults in electronic order templates affect
      physicians' treatment decisions and medical errors. METHODS: Forty-five medical
      residents completed order sets for 3 medical case studies. Participants were
      randomly assigned to receive order sets with either "opt-in" defaults (options
      visible but unselected) or "opt-out" defaults (options visible and preselected).
      RESULTS: compare error rates between conditions and examine the type and severity
      of errors most often made with opt-in versus opt-out defaults. Results. Opt-out
      defaults resulted in a greater number of items ordered and specifically increased
      commission errors (overordering) compared with opt-in defaults. However, while
      opt-in defaults resulted in fewer orders, they also increased omission errors.
      When the severity of the errors is taken into account, the default effects seem
      limited to less severe errors. CONCLUSION: The defaults used in electronic order
      sets influence medical treatment decisions when the consequences to a patient's
      health are low. This pattern suggests that physicians cognitively override
      incorrect default choices but only to a point, and it implies tradeoffs that
      maximize accuracy and minimize cognitive effort. Results indicate that defaults
      for low-impact items on electronic templates warrant careful attention because
      physicians are unlikely to override them.

PMID- 24125791
TI  - Age-related variability in performance of a motor action selection task is
      related to differences in brain function and structure among older adults.
AB  - Task performance for behaviors that engage motor cognitive processes may be
      particularly sensitive to age-related changes. One well-studied model of
      cognitive motor function involves engagement of action selection (AS) processes.
      In young adults, task conditions that add AS demands result in increased
      preparation times and greater engagement of bilateral dorsal premotor (PMd) and
      parietal cortices. The current study investigated the behavioral and neural
      response to a change in motor cognitive demands in older adults through the
      addition of AS to a movement task. Sixteen older adults made a joystick movement
      under two conditions during functional magnetic resonance imaging. In the AS
      condition, participants moved right or left based on an abstract rule; in the
      execution only (EO) condition, participants moved in the same direction on every
      trial. Across participants, the AS condition, as compared to the EO condition,
      was associated with longer reaction time and increased activation of left
      inferior parietal lobule. Variability in behavioral response to the AS task
      between participants related to differences in brain function and structure.
      Overall, individuals with poorer AS task performance showed greater activation in
      left PMd and dorsolateral prefrontal cortex and decreased structural integrity of
      white matter tracts that connect sensorimotor, frontal, and parietal regions-key
      regions for AS task performance. Additionally, two distinct patterns of
      functional connectivity were found. Participants with a pattern of decreased
      primary motor-PMd connectivity in response to the AS condition, compared to those
      with a pattern of increased connectivity, were older and had poorer behavioral
      performance. These neural changes in response to increased motor cognitive
      demands may be a marker for age-related changes in the motor system and have an
      impact on the learning of novel, complex motor skills in older adults. 

PMID- 24125793
TI  - Early miscarriage during Sweet's syndrome: uncommon, but probably not
      coincidental.

PMID- 24125794
TI  - Potential of anaerobic digestion for material recovery and energy production in
      waste biomass from a poultry slaughterhouse.
AB  - This study was carried out to assess the material and energy recovery by organic
      solid wastes generated from a poultry slaughterhouse. In a poultry slaughterhouse
      involving the slaughtering of 100,000 heads per day, poultry manure & feather
      from the mooring stage, blood from the bleeding stage, intestine residue from the
      evisceration stage, and sludge cake from the wastewater treatment plant were
      discharged at a unit of 0.24, 4.6, 22.8, and 2.2 Mg day(-1), consecutively. The
      amount of nitrogen obtained from the poultry slaughterhouse was 22.36 kg 1000
      head(-1), phosphate and potash were 0.194 kg 1000 head(-1) and 0.459 kg 1000
      head(-1), respectively. As regards nitrogen recovery, the bleeding and
      evisceration stages accounted for 28.0% and 65.8% of the total amount of
      recovered nitrogen. Energy recovered from the poultry slaughterhouse was 35.4
      Nm(3) 1000 head(-1) as CH4. Moreover, evisceration and wastewater treatment stage
      occupied 88.1% and 7.2% of the total recovered CH4 amount, respectively.

PMID- 24125795
TI  - Experimental investigation of wood combustion in a fixed bed with hot air.
AB  - Waste combustion on a grate with energy recovery is an important pillar of
      municipal solid waste (MSW) management in the Netherlands. In MSW incinerators
      fresh waste stacked on a grate enters the combustion chamber, heats up by
      radiation from the flame above the layer and ignition occurs. Typically, the
      reaction zone starts at the top of the waste layer and propagates downwards,
      producing heat for drying and devolatilization of the fresh waste below it until
      the ignition front reaches the grate. The control of this process is mainly based
      on empiricism. MSW is a highly inhomogeneous fuel with continuous fluctuating
      moisture content, heating value and chemical composition. The resulting process
      fluctuations may cause process control difficulties, fouling and corrosion
      issues, extra maintenance, and unplanned stops. In the new concept the fuel layer
      is ignited by means of preheated air (T>220  degrees C) from below without any
      external ignition source. As a result a combustion front will be formed close to
      the grate and will propagate upwards. That is why this approach is denoted by
      upward combustion. Experimental research has been carried out in a batch reactor
      with height of 4.55 m, an inner diameter of 200 mm and a fuel layer height up to
      1m. Due to a high quality two-layer insulation adiabatic conditions can be
      assumed. The primary air can be preheated up to 350  degrees C, and the secondary
      air is distributed via nozzles above the waste layer. During the experiments,
      temperatures along the height of the reactor, gas composition and total weight
      decrease are continuously monitored. The influence of the primary air speed, fuel
      moisture and inert content on the combustion characteristics (ignition rate,
      combustion rate, ignition front speed and temperature of the reaction zone) is
      evaluated. The upward combustion concept decouples the drying, devolatilization
      and burnout phase. In this way the moisture and inert content of the waste have
      almost no influence on the combustion process. In this paper an experimental
      comparison between conventional and reversed combustion is presented.

PMID- 24125792
TI  - Fearful faces heighten the cortical representation of contextual threat.
AB  - Perception of facial expressions is typically investigated by presenting isolated
      face stimuli. In everyday life, however, faces are rarely seen without a
      surrounding visual context that affects perception and interpretation of the
      facial expression. Conversely, fearful faces may act as a cue, heightening the
      sensitivity of the visual system to effectively detect potential threat in the
      environment. In the present study, we used steady-state visually evoked
      potentials (ssVEPs) to examine the mutual effects of facial expressions (fearful,
      neutral, happy) and affective visual context (pleasant, neutral, threat). By
      assigning two different flicker frequencies (12 vs. 15Hz) to the face and the
      visual context scene, cortical activity to the concurrent stimuli was separated,
      which represents a novel approach to independently tracking the cortical
      processes associated with the face and the context. Twenty healthy students
      viewed flickering faces overlaid on flickering visual scenes, while performing a
      simple change-detection task at fixation, and high-density EEG was recorded.
      Arousing background scenes generally drove larger ssVEP amplitudes than neutral
      scenes. Importantly, background and expression interacted: When viewing fearful
      facial expressions, the ssVEP in response to threat context was amplified
      compared to other backgrounds. Together, these findings suggest that fearful
      faces elicit vigilance for potential threat in the visual periphery. 

PMID- 24125796
TI  - Implantable defibrillators improve survival in patients with mildly symptomatic
      heart failure receiving cardiac resynchronization therapy: analysis of the long
      term follow-up of remodeling in systolic left ventricular dysfunction (REVERSE).
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves
      functional status, and induces reverse left ventricular remodeling in selected
      populations with heart failure. These benefits have been noted with both CRT
      pacemakers as well as those devices with defibrillator backup (CRT-D). However,
      there are little data comparing mortality between these 2 device types. METHODS
      AND RESULTS: REsynchronization reVErses Remodeling in Systolic left vEntricular
      dysfunction (REVERSE) was a multicenter, randomized trial of CRT among patients
      with mild heart failure. Long-term annual follow-up for 5 years was preplanned.
      The present analysis was confined to the 419 patients who were randomized to
      active CRT group. CRT-pacemakers or CRT-D devices were implanted based on
      national guidelines at the time of enrollment, with 74 patients receiving CRT
      pacemaker devices and the remaining 345 patients receiving CRT-D devices. After
      12 months of CRT, changes in the clinical composite score, left ventricular end
      systolic volume index, 6-minute walk time, and quality of life indices were
      similar between CRT pacemaker and CRT-D patients. However, long-term follow-up
      showed lower morality in the CRT-D group. Specifically, multivariable analysis
      showed that CRT-D (hazard ratio, 0.35; P=0.003) was a strong independent
      predictor of survival. Female sex, longer unpaced QRS duration, and smaller
      baseline left ventricular end systolic volume index also were also associated
      with better survival. CONCLUSIONS: REVERSE demonstrated that the addition of
      implantable cardioverter-defibrillator therapy to CRT is associated with improved
      long-term survival compared with CRT pacing alone in mild heart failure. CLINICAL
      TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique Identifier:
      NCT00271154.

PMID- 24125797
TI  - Biokinetic and molecular studies of methanogens in phased anaerobic digestion
      systems.
AB  - The influence of differing operational conditions of two-stage digesters on
      biokinetic characteristics and communities of methanogenic archaea was evaluated.
      Operating temperature of each phase influenced the archaeal communities
      significantly. Also, a strong correlation was observed between community
      composition and temperature and pH. The maximum specific substrate utilization
      rates (k max) of acetoclastic methanogens in the mesophilic and thermophilic 1st
      phases were 11.4 and 22.0 mgCOD mgCOD(-1)d(-1), respectively, whereas
      significantly lower k max values were estimated for the mesophilic and
      thermophilic 2nd-phase digesters which were 7.6 and 16.6 mgCOD mgCOD(-1)d(-1),
      respectively. It appeared that the biokinetic characteristics of the acetoclastic
      methanogen communities were reliant on digester loading rates. Also, higher
      temperature dependency coefficients (theta) were observed for the long retention
      time digesters when compared to the values computed for the 1st-phase digesters.
      Accordingly, the implementation of two sets of biokinetic parameters for
      acetoclastic methanogen will improve modeling of phased anaerobic digesters.

PMID- 24125798
TI  - A novel whole-phase succinate fermentation strategy with high volumetric
      productivity in engineered Escherichia coli.
AB  - The strategic design of this study aims at fermentative succinate production with
      high volumetric productivity in engineered Escherichia coli. An E. coli
      YL106/pSCsfcA was engineered to produce succinate under aerobic, microaerobic and
      anaerobic conditions by derepressing the inhibition of low dissolved oxygen,
      eliminating the NADH competitive pathways, modulating the redistribution of
      metabolic flux, and increasing the transport rate of the sole carbon source
      glucose. Based on this strain, a novel "whole-phase" succinate production
      strategy was further developed, in which the engineered strain was first
      cultivated aerobically, then shifted to microaerobic phase at the end of
      exponential growth, and finally kept in anaerobic phase until the end of
      fermentation. Employing this strategy, the engineered E. coli YL106/pSCsfcA was
      able to produce 85.30 g l(-1) succinate with an overall volumetric productivity
      of 2.13 g l(-1)h(-1). This process offers an efficiently fermentative method for
      industrial succinate production in metabolically engineered E. coli.

PMID- 24125799
TI  - Firebase medicine: extending the Role I aid station.
AB  - The unique nature of counterinsurgency warfare in Afghanistan highlights the
      tactical and technical challenges of the non-contiguous battlefield. Although
      remote military outposts distant from their support hubs help project NATO power,
      they also operate without the advantages of a secure rear area or interior lines
      of communication. Commonly referred to as 'firebases', these outposts typically
      house a platoon or company-sized element and present numerous challenges to the
      delivery of medical care and support. Medical planners and providers can mitigate
      many of these inherent risks through targeted interventions designed to increase
      the capabilities of these remote outposts. These interventions include focused
      higher-level trauma and non-trauma medical training for both medical and non
      medical personnel, expanded equipment lists, ongoing medical education, training
      and rehearsals, and a proven and redundant communications plan. 

PMID- 24125800
TI  - Medical management of Captured Persons.
AB  - In most conflicts there is the potential that there will be Captured Persons
      (CPERS) whose medical care is the responsibility of the capturing army. The
      standard of this care should be to the same standard as that afforded to one's
      own troops. However the medical practicalities of maintaining such standards can
      be difficult. This article reviews the practicalities of the medical care of
      CPERS as part of the UK deployment in Afghanistan on Operation HERRICK. 

PMID- 24125801
TI  - Brachial plexus palsy following a training run with a heavy backpack.
AB  - A 23-year-old male British soldier developed a progressive sensory loss and
      weakness in his right arm during a 12 km training run with a load of
      approximately 70 kg. There was no recovery of his symptoms within 3 months and
      both MRI and USS did not demonstrate a site of compression within the brachial
      plexus. An infraclavicular brachial plexus exploration was performed 11 months
      after injury that indicated an ischaemic neuropathy with post-injury fibrosis.
      Injuries of the brachial plexus secondary to carrying a heavy backpack during
      prolonged periods of exercise are rare, particularly in the infraclavicular
      region. Cases such as this highlight that training regimens within the military
      population should be appraised due to the risk of similar injuries occurring. 

PMID- 24125802
TI  - Specific sleepiness symptoms are indicators of performance impairment during
      sleep deprivation.
AB  - Drivers are not always aware that they are becoming impaired as a result of
      sleepiness. Using specific symptoms of sleepiness might assist with recognition
      of drowsiness related impairment and help drivers judge whether they are safe to
      drive a vehicle, however this has not been evaluated. In this study, 20 healthy
      volunteer professional drivers completed two randomized sessions in the
      laboratory - one under 24h of acute sleep deprivation, and one with alcohol. The
      Psychomotor Vigilance Task (PVT) and a 30min simulated driving task (AusEdTM)
      were performed every 3-4h in the sleep deprivation session, and at a BAC of 0.00%
      and 0.05% in the alcohol session, while electroencephalography (EEG) and eye
      movements were recorded. After each test session, drivers completed the
      Karolinska Sleepiness Scale (KSS) and the Sleepiness Symptoms Questionnaire
      (SSQ), which includes eight specific sleepiness and driving performance symptoms.
      A second baseline session was completed on a separate day by the professional
      drivers and in an additional 20 non-professional drivers for test-retest
      reliability. There was moderate test-retest agreement on the SSQ (r=0.59).
      Significant correlations were identified between individual sleepiness symptoms
      and the KSS score (r values 0.50-0.74, p<0.01 for all symptoms). The frequency of
      all SSQ items increased during sleep deprivation (chi(2) values of 28.4-80.2,
      p<0.01 for all symptoms) and symptoms were related to increased subjective
      sleepiness and performance deterioration. The symptoms "struggling to keep your
      eyes open", "difficulty maintaining correct speed", "reactions were slow" and
      "head dropping down" were most closely related to increased alpha and theta
      activity on EEG (r values 0.49-0.59, p<0.001) and "nodding off to sleep" and
      "struggling to keep your eyes open" were related to slow eye movements (r values
      0.67 and 0.64, p<0.001). Symptoms related to visual disturbance and impaired
      driving performance were most accurate at detecting severely impaired driving
      performance (AUC on ROC curve of 0.86-0.91 for detecting change in lateral lane
      position greater than the change at a BAC of 0.05%). Individual sleepiness
      symptoms are related to impairment during acute sleep deprivation and might be
      able to assist drivers in recognizing their own sleepiness and ability to drive
      safely. 

PMID- 24125803
TI  - Generalized nonlinear models for rear-end crash risk analysis.
AB  - A generalized nonlinear model (GNM)-based approach for modeling highway rear-end
      crash risk is formulated using Washington State traffic safety data. Previous
      studies majorly focused on causal factor identification and crash risk modeling
      using Generalized linear Models (GLMs), such as Poisson regression, Logistic
      regression, etc. However, their basic assumption of a generalized linear
      relationship between the dependent variable (for example, crash rate) and
      independent variables (for example, contribute factors to crashes) established
      via a link function can be often violated in reality. Consequently, the GLM-based
      modeling results could provide biased findings and conclusions. In this research,
      a GNM-based approach is developed to utilize a nonlinear regression function to
      better elaborate non-monotonic relationships between the independent and
      dependent variables using the rear end accident data collected from 10 highway
      routes from 2002 through 2006. The results show for example that truck percentage
      and grade have a parabolic impact: they increase crash risks initially, but
      decrease them after the certain thresholds. Such non-monotonic relationships
      cannot be captured by regular GLMs which further demonstrate the flexibility of
      GNM-based approaches in the nonlinear relationship among data and providing more
      reasonable explanations. The superior GNM-based model interpretations help better
      understand the parabolic impacts of some specific contributing factors for
      selecting and evaluating rear-end crash safety improvement plans. 

PMID- 24125804
TI  - Long-term type 1 diabetes impairs decidualization and extracellular matrix
      remodeling during early embryonic development in mice.
AB  - INTRODUCTION: Endometrial decidualization and associated extracellular matrix
      (ECM) remodeling are critical events to the establishment of the maternal-fetal
      interface and successful pregnancy. Here, we investigated the impact of type 1
      diabetes on these processes during early embryonic development, in order to
      contribute to the understanding of the maternal factors associated to diabetic
      embryopathies. METHODS: Alloxan-induced diabetic Swiss female mice were bred
      after different periods of time to determine the effects of diabetes progression
      on the development of gestational complications. Furthermore, the analyses
      focused on decidual development as well as mRNA expression, protein deposition
      and ultrastructural organization of decidual ECM. RESULTS: Decreased number of
      implantation sites and decidual dimensions were observed in the group mated 90
      110 days after diabetes induction (D), but not in the 50-70D group. Picrosirius
      staining showed augmentation in the fibrillar collagen network in the 90-110D
      group and, following immunohistochemical examination, that this was associated
      with increase in types I and V collagens and decrease in type III collagen and
      collagen-associated proteoglycans biglycan and lumican. qPCR, however,
      demonstrated that only type I collagen mRNA levels were increased in the diabetic
      group. Alterations in the molecular ratio among distinct collagen types and
      proteoglycans were associated with abnormal collagen fibrillogenesis, analyzed by
      transmission electron microscopy. CONCLUSIONS: Our results support the concept
      that the development of pregnancy complications is directly related with duration
      of diabetes (progression of the disease), and that this is a consequence of both
      systemic factors (i.e. disturbed maternal endocrine-metabolic profile) and
      uterine factors, including impaired decidualization and ECM remodeling.

PMID- 24125805
TI  - Analysis of differentially expressed genes in placental tissues of preeclampsia
      patients using microarray combined with the Connectivity Map database.
AB  - Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant
      maternal and neonatal morbidity and mortality. To better understand the
      pathophysiology of PE, the gene expression profiles of placental tissue from 5
      controls and 5 PE patients were assessed using microarray. A total of 224
      transcripts were significantly differentially expressed (>2-fold change and q
      value <0.05, SAM software). Gene Ontology (GO) enrichment analysis indicated that
      genes involved in hypoxia and oxidative and reductive processes were
      significantly changed. Three differentially expressed genes (DEGs) involved in
      these biological processes were further verified by quantitative real-time PCR.
      Finally, the potential therapeutic agents for PE were explored via the
      Connectivity Map database. In conclusion, the data obtained in this study might
      provide clues to better understand the pathophysiology of PE and to identify
      potential therapeutic agents for PE patients.

PMID- 24125806
TI  - The effect of delay in collection and processing on RNA integrity in human
      placenta: experiences from rural Africa.
AB  - This paper examines the relationship between time to processing and RNA quality
      in placentas collected from women in a field setting in rural Gambia. Placental
      samples were collected from the villages and transferred to the laboratory. RNA
      was extracted using Trizol and integrity assessed using the RNA integrity number
      (RIN). Values were inversely correlated with delay in processing. Expression
      levels of candidate genes increased with decreasing RIN. Normalising to a
      housekeeper gene removed this artefact. We propose a cut-off point of 90 min from
      delivery, after which samples cannot be used for gene expression analysis. 

PMID- 24125807
TI  - Cortical and white matter alterations in patients with neuropathic pain after
      spinal cord injury.
AB  - Neuropathic pain is one of the major problems of patients with spinal cord injury
      (SCI), which remains refractory to treatment despite a variety of therapeutic
      approach. Multimodal neuroimaging could provide complementary information for
      brain mechanisms underlying neuropathic pain, which could be based on development
      of more effective treatment strategies. Ten patients suffering from chronic
      neuropathic pain after SCI and 10 healthy controls underwent FDG-PET, T1
      anatomical MRI and diffusion tensor imaging. We found decreases of both
      metabolism and the gray matter volume in the left dorsolateral prefrontal cortex
      in patients compared to healthy controls, as well as hypometabolism in the medial
      prefrontal cortex and gray matter volume loss in bilateral anterior insulae and
      subgenual anterior cingulate cortices. These brain regions are generally known to
      participate in pain modulation by affective and cognitive processes. Decreases of
      mean diffusivity (MD) in the right internal capsule including, cerebral peduncle,
      pre-and post-central white matter, and prefrontal white matter as components of
      the corticospinal and thalamocortical tracts were demonstrated in patients.
      Further, lower MD value of prefrontal white matter was correlated with decreased
      metabolism of medial prefrontal cortex in patients. These results indicated that
      white matter changes imply abnormal pain modulation in patients as well as motor
      impairment. Our study showed the functional and structural multimodal imaging
      modality commonly identified the possible abnormalities in the brain regions
      participating pain modulation in neuropathic pain. Multifaceted imaging studies
      in neuropathic pain could be useful elucidating precise mechanisms of persistent
      pain, and providing future directions for treatment. 

PMID- 24125809
TI  - Protein kinase A regulates the long-term potentiation of intrinsic excitability
      in neonatal trigeminal motoneurons.
AB  - Although much is known about neuronal plasticity in the mammalian hippocampus and
      other cortical neurons, the subcellular mechanisms underlying plasticity at the
      level of motor pools are less well characterized. Protein kinase A (PKA)
      activation plays an essential role in long-term potentiation of intrinsic
      excitability (LTP-IE) in layer V (LV) visual cortical neurons and may be involved
      in other systems as well. Trigeminal motoneurons (TMNs) participate in rhythmical
      motor behaviors, such as suckling, chewing, and swallowing. Using the whole-cell
      patch clamp method and various kinase inhibitors and activators, we investigated
      the mechanism of LTP-IE in neonatal rat TMNs. Ca(2+) depletion using ACSF with
      0mM Ca(2+) or the Ca(2+) chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid
      (BAPTA) blocked the long-lasting increase in intrinsic excitability in TMNs,
      showing that intracellular Ca(2+) during the induction protocol is necessary for
      the induction of LTP-IE. We next used specific inhibitors of PKA, protein kinase
      C, and calcium/calmodulin-dependent protein kinase II during the induction
      protocol. Only the PKA inhibitor H-89 blocked the increase in the firing rate
      induced by the induction protocol. In addition, forskolin, which activates PKA,
      induced a long-lasting increase in excitability that resembled the excitability
      produced by the induction protocol. Thus, we conclude that LTP-IE in TMNs is
      calcium-dependent, and PKA is the primary regulator of this process. 

PMID- 24125808
TI  - Thalamic post-inhibitory bursting occurs in patients with organic dystonia more
      often than controls.
AB  - We now test the hypothesis that post-inhibitory bursting in the human pallidal
      receiving nucleus of the thalamus (ventral oral) mediates inhibitory pallido
      thalamic transmission during dystonia. We have compared thalamic single neuron
      activity in nine patients with organic dystonia to that in a patient with
      psychogenic dystonia (Psyd) and in healthy waking monkeys. In organic dystonia,
      EMG power is commonly concentrated at the lowest frequency of the smoothed
      autopower spectrum (0.39Hz). Therefore, segments of spike trains with a signal-to
      noise ratio >=2 at 0.39Hz were termed dystonia frequency (DF) segments, which
      occurred more commonly during dystonia related to movement. Those with a SNR<2
      were termed non-dystonia frequency (nDF) segments, which were associated with
      spontaneous dystonia. We concentrated on nDF activity since neuronal activity in
      our controls was measured at rest. Neuronal spike trains were categorized into
      those with post-inhibitory bursts (G, grouped), with single spikes (NG, non
      grouped), or with both single spikes and bursts (I, intermediate). nDF spike
      trains in ventral oral had more G category firing in dystonia than in controls.
      The burst rate and the pre-burst silent period in nDF firing of organic dystonia
      were consistently greater than those of both the monkeys and the patient with
      Psyd. The distribution of the pre-burst silent period was bimodal with a longer
      mode of approximately GABAb (gamma amino butyric acid receptor-type b) duration.
      These results demonstrate distinct differences of post-inhibitory bursting in
      organic dystonia versus controls. The presence of inhibitory events consistent
      with GABAb duration suggests interventions for treatment of dystonia. 

PMID- 24125810
TI  - Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal
      cord contributes to chronic visceral pain in rats.
AB  - The roles of spinal N-methyl-d-aspartic acid receptor 2B (NR2B) subunit in
      central sensitization of chronic visceral pain were investigated. A rat model
      with irritable bowel syndrome (IBS) was established by colorectal distention
      (CRD) on post-natal days 8-14. Responses of the external oblique muscle of the
      abdomen to CRD were measured to evaluate the sensitivity of visceral pain in
      rats. The sensitivity of visceral pain significantly increased in IBS-like rats.
      Expressions of spinal NR2B subunit and phosphorylated NR2B subunit significantly
      increased by 50-55% in IBS-like rats when compared with those in control rats. Ro
      25-6981, a selective antagonist of NR2B subunit, has a dose-dependent anti
      allodynic and anti-hyperalgesic effect without causing motor dysfunction in IBS
      like rats. Furthermore, the activation mechanism of the spinal NR2B subunit in
      chronic visceral pain was also investigated. Spinal administration of genistein,
      a specific inhibitor of tyrosine kinases, also decreased the visceral pain
      hypersensitivity of IBS-like rats in a dose-dependent manner. In addition, the
      expression of phosphorylated NR2B subunit was decreased after spinal
      administration of Ro 25-6981 or genistein in IBS-like rats. In conclusion,
      tyrosine kinase activation-induced phosphorylation of NR2B subunit may play a
      crucial role in central sensitization of chronic visceral pain. 

PMID- 24125811
TI  - Jaw-opening and -closing premotoneurons in the nucleus of the solitary tract
      making contacts with laryngeal and pharyngeal afferent terminals in rats.
AB  - This study clarified the neural mechanisms underlying jaw movements in
      pharyngolaryngeal reflexes such as swallowing in rats. After retrograde tracer
      injections into the ventromedial division (Vmovm) of the trigeminal motor nucleus
      (Vmo) containing jaw-opening (JO) motoneurons or into the dorsolateral division
      (Vmodl) of Vmo containing jaw-closing (JC) motoneurons, JO and JC premotoneurons
      were labeled with an ipsilateral predominance in the medial and intermediate
      subnuclei of the rostrocaudal middle two-thirds of the nucleus of the solitary
      tract (Sol); JC premotoneurons were also in the lateral subnucleus of Sol. After
      anterograde tracer injections into the Sol, axons were labeled with an
      ipsilateral predominance in the Vmovm and Vmodl, prominently in the ipsilateral
      Vmovm. After transganglionic tracer applications to the superior laryngeal nerve
      (SLN) or the cervical trunk of the glossopharyngeal nerve (GpN-ct), labeled
      afferents were seen in the medial, intermediate, lateral and interstitial
      subnuclei of Sol at the rostral three-fourths of Sol, indicating considerable
      overlap with the JO and JC premotoneurons in the Sol. Double labeling experiments
      demonstrated contacts between the afferent terminals and the JO and JC
      premotoneurons. The present study has for the first time revealed the
      differential distribution of JO and JC premotoneurons in the Sol and features of
      their projections from the Sol, as well as their connections with SLN and GpN-ct
      afferent inputs. The JO and JC premotoneurons in the Sol may play an important
      role in generation and organization of jaw movements in pharyngolaryngeal
      reflexes evoked by SLN and GpN-ct inputs, such as swallowing. 

PMID- 24125812
TI  - Two patients with a GRIN2A mutation and childhood-onset epilepsy.
AB  - BACKGROUND: N-methyl-D-aspartate is a key neurotransmitter within the central
      nervous system and its dysfunction can play an important role in epilepsy.
      Mutations of genes involving the N-methyl-D-aspartate receptor have been
      implicated in a wide variety of neuropsychiatric disorders including epilepsy,
      specifically, within the glutamate receptor ionotropic N-methyl-D-aspartate 2A
      (GRIN2A). PATIENTS: We report two patients with a glutamate receptor ionotropic N
      methyl-D-aspartate 2A mutation who presented with epilepsy. CONCLUSIONS:
      Individuals with a glutamate receptor ionotropic N-methyl-D-aspartate 2A mutation
      exhibit a broad clinical spectrum.

PMID- 24125813
TI  - Carpal tunnel syndrome in children.
AB  - BACKGROUND: Carpal tunnel syndrome or median neuropathy at the wrist is a rare
      condition in children. Of the reported patients with carpal tunnel syndrome,
      mucopolysaccharidoses and the mucolipidoses are the most common causes. PATIENTS:
      We report 13 patients between the ages of 2 and 17 years of age with carpal
      tunnel syndrome. RESULTS: Mucopolysaccharidoses was the cause in one child. In
      other children, trauma to the median nerve, malformations of the wrist, brachial
      plexopathy, obesity, inherited susceptibility to pressure palsies (PMP 22 gene
      deletion), and family history of median neuropathy at the wrist were identified.
      All patients had hand pain, numbness, and paresthesias in their hands. The nerve
      conduction studies showed prolongation of median sensory nerve latency and distal
      motor latency in median nerve. CONCLUSIONS: Carpal tunnel syndrome occurs in
      children and a variety of risk factors predispose to its occurrence.

PMID- 24125814
TI  - Correcting for demographic variables on the modified telephone interview for
      cognitive status.
AB  - OBJECTIVE: To examine the effect of demographic variables on scores on the
      modified Telephone Interview for Cognitive Status (mTICS) in a healthy cohort and
      develop demographically corrected normative data. DESIGN: Observational. SETTING:
      Primarily academic medical centers. PARTICIPANTS: 576 healthy older adults.
      MEASUREMENTS: mTICS. RESULTS: Age and education significantly correlated with
      mTICS score, and sex differences were also observed on this score. Ethnicity
      differences were not observed. Using regression equations, age, education, and
      sex significantly predicted mTICS total score. CONCLUSIONS: By using these
      corrections, an individual's cognitive status may be more accurately predicted
      with this telephone screening instrument, although clinical validation is needed.

PMID- 24125815
TI  - Racial/ethnic variations in the relation between body mass index and cognitive
      function among older adults.
AB  - OBJECTIVES: The present study examines racial/ethnic variations in the relation
      between body mass index (BMI) and cognitive function among older adults. DESIGN:
      Cross-sectional study of secondary data. SETTING: Data were obtained from the
      2010 Health and Retirement Study. PARTICIPANTS: Racial/ethnic groups analyzed
      were black (n = 546), Hispanic (n = 110), and non-Hispanic white (n = 4,104).
      MEASUREMENTS: BMI was calculated based on self-reported height and weight.
      Cognitive function was measured based on Telephone Interview for Cognitive Status
      Health and Retirement Study version scores. RESULTS: Significant main effects
      were found for both BMI and race/ethnicity, indicating that cognitive function
      varies significantly by both. The BMI * race/ethnicity interaction was also found
      to be significant. The interaction revealed that among the white sample cognitive
      function scores tended to increase as BMI increased whereas the opposite relation
      was observed in the Hispanic sample. The black sample displayed a similar pattern
      as the white sample, although a decrease was observed in cognitive function
      scores once BMI reached obesity. CONCLUSION: The results suggest that the
      relation between BMI and cognitive function does vary by race ethnicity.
      Therefore, it can be concluded that high or low BMI may vary as a risk or
      protective factor for cognitive dysfunction among older adults by race/ethnicity.
      Implications for research and clinical work are discussed.

PMID- 24125817
TI  - [Current situation and problems associated with inactivation of microorganisms in
      water using copper].
AB  - OBJECTIVES: The current situation and problems associated with inactivation of
      microorganisms in water using copper were elucidated. METHODS: A literature
      review was conducted regarding the history and mechanisms of inactivation
      technology using copper, the variety of microorganisms shown to be inactivated by
      these methods in previous experiments, and the efficacy of such technologies for
      the inactivation of microorganisms in water. RESULTS: The use of copper for
      inactivation of microorganisms has a long history. Although the use of copper was
      discontinued temporarily owing to the advent of antibiotics in the 1930s, the
      occurrence of antibiotic-resistant bacteria has resulted in the need for
      different approaches to control pathogenic microorganisms. One such alternative
      is the use of copper. Although the mechanisms underlying the efficacy of copper
      inactivation technology have not yet been elucidated in detail, it has been
      suggested that pathogenic bacteria are inactivated due to the toxicity of copper
      ions and strong oxidation effects of reactive oxygen species. Copper inactivation
      technology is effective against many pathogenic microorganisms that pose a risk
      to public health, such as Legionella pneumophila, Salmonella enterica, and
      Mycobacterium tuberculosis. In recent years, copper inactivation technology has
      been used in various water-related devices, especially water supply pipes in
      buildings. Previous studies have demonstrated that microorganisms can be
      sufficiently inactivated by copper even at concentrations below that specified in
      the Water Quality Standard for Drinking Water. However, some previous studies
      have indicated that the inactivation effect of copper is short-lived. Therefore,
      the development of techniques to maintain a long-term inactivation effect is a
      key concern. In addition, it has been reported that the use of copper pipes
      triggers chlorine decay and results in the formation of chlorine disinfection
      byproducts. Hence, further studies should aim at assessing the risks and benefits
      associated with the use of copper. CONCLUSION: Although the practical issues
      regarding copper inactivation technology are persistent, this method has been
      demonstrated to be efficacious. Therefore, this technology could be expected to
      be used in many devices such as water supply systems in hospitals in the near
      future.

PMID- 24125816
TI  - Race-related differences in depression onset and recovery in older persons over
      time: the health, aging, and body composition study.
AB  - OBJECTIVES: To evaluate race-related differences in depression onset and recovery
      in older persons, overall and by sex, and examine race-related differences in
      mortality according to depression. DESIGN: Prospective cohort study. SETTING:
      General community in pre-designated zip code areas in Memphis, Tennessee, and
      Pittsburgh, Pennsylvania. PARTICIPANTS: 3,075 persons aged 70-79 years at
      baseline in the Health, Aging, and Body Composition study. MEASUREMENTS:
      Depression was assessed at eight time points over 10 years using the 10-item
      Center for Epidemiologic Studies-Depression scale; patients were categorized as
      nondepressed (score less than 8) or depressed (score of 8 or higher). We created
      variables for transitions across each 18-month time interval, namely, from
      nondepressed or depressed to nondepressed, depressed, or death, and determined
      the association between race and the average likelihood of these transitions over
      time. RESULTS: A higher percentage of blacks than whites were depressed at nearly
      all time points. Adjusting for demographics, common chronic conditions, and body
      mass index, blacks had a higher likelihood of experiencing depression onset than
      whites (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.03-1.43); among
      men, blacks were more likely to experience depression onset than whites (OR:
      1.44; 95% CI: 1.24-2.89). Blacks also had a higher likelihood of transitioning
      from nondepressed to death (OR: 1.79; 95% CI: 1.30-2.46). Overall and in sex
      stratified analyses, race was not associated with recovery from depression or
      with the transition from depression to death. CONCLUSION: Our findings highlight
      race differences in depression in older persons and encourage further research on
      the course of depression in older black patients.

PMID- 24125818
TI  - [Introduction of long-term care insurance: changes in service usage].
AB  - OBJECTIVES: With the aging of the population, Japan's long-term care system has
      shifted from a welfare-placement system to a social-insurance system, which is a
      precedent of policies for the elderly. We examined how individuals who used care
      services before the implementation of long-term care insurance (LTCI) (previous
      service users) currently use the LTCI services, with a focus on the processes of
      service use. METHODS: Panel data were obtained from the Nihon University Japanese
      Longitudinal Study of Aging database. These data were collected by interviews
      conducted before (November 1999 and March 2000) and after (November 2001 and
      December 2001) the establishment of LTCI. Among the 3992 individuals who
      participated in these interviews, 416 of the previous service users, aged >=65
      years, were sampled. The outcome measures were the processes of using LTCI
      services (application for LTCI, certification of long-term care need, and
      contract with LTCI service providers). Logistic regression analysis was performed
      to identify individual factors associated with the process of application for
      LTCI. RESULTS: There were 133 LTCI users among the 416 previous service users
      (32.0%). Of the service processes used, 45.5% of previous service users were
      applicants, 85.7% of the applicants were certified individuals, and 88.7% of
      those certified used services with service contracts. The application process was
      significantly easier for individuals with disease (odds ratio[OR], 8.34 : 95%
      confidence interval [CI], 1.86-37.46), those dependent for their instrumental
      activities of daily living (IADL) (OR, 11.21 : 95% CI, 5.22-24.07), those with an
      equivalent income of <1.25 million yen (OR, 2.72 : 95% CI, 1.30-5.69), and those
      who had used respite care (OR, 3.29 : 95% CI, 1.16-9.35) previously. In contrast,
      the application process was significantly difficult for community rehabilitation
      users (OR, 0.38 : 95% CI, 0.17-0.82). CONCLUSION: Only half of the previous
      service users were applicants, and they had severe diseases or were more
      dependent for their IADL. Our findings suggest that many individuals who were
      functionally independent were covered under the welfare-placement system.
      Additionally, low-income individuals did not refrain from applying.

PMID- 24125819
TI  - [A 10-year community intervention for disability prevention and its effect on
      healthy aging in Kusatsu town].

PMID- 24125820
TI  - [Attitude towards power shortage and perceived changes in physical activity].

PMID- 24125821
TI  - [The effect of increasing tobacco tax on tobacco sales in Japan].
AB  - OBJECTIVES: Since the special tobacco tax was established in 1998, the tobacco
      tax and price of tobacco have increased thrice, in 2003, 2006, and 2010,
      respectively. We evaluated the effect of increases in tax on the consumption and
      sales of tobacco in Japan using the annual data on the number of tobacco products
      sold and the total sales from Japan Tobacco, Inc. METHODS: We applied the number
      of tobacco products sold and the total sales per year to a joinpoint regression
      model to examine the trends in the data. This model could help identify the year
      in which a decrease or increase was apparent from the data. In addition, we
      examined the effect of each tax increase while also considering other factors
      that may have caused a decrease in the levels of tobacco consumption using the
      method proposed by Hirano et al. RESULTS: According to the joinpoint regression
      analysis, the number of tobacco products sold started decreasing in 1998, and the
      trends of decrease accelerated to 5% per year, from 2005. Owing to the tax
      increase, tobacco sales reduced by -2.4%, -2.9%, and -10.1% (corrected for the
      effect of the Tohoku Great Earthquake), and price elasticity was estimated as 
      0.30, -0.27, and -0.28 (corrected) in 2003, 2006, and 2010, respectively. The
      effect of tobacco tax increase on the decrease in tobacco sales was greatest in
      2010, while the price elasticity remained almost the same as it was during the
      previous tax increase. CONCLUSION: The sharp hike in tobacco tax in 2010
      decreased the number of tobacco products sold, while the price elasticity in 2010
      was similar to that in 2003 and 2006. Our findings suggest that further increase
      in tobacco tax is needed to reduce the damage caused by smoking in the people of
      Japan.

PMID- 24125822
TI  - Management of short bowel syndrome in infancy.
AB  - Short bowel syndrome (SBS) is a reduction in functioning bowel length which is
      most often a result of surgical resection. Risk factors in the neonatal period
      include necrotising enterocolitis, small bowel atresia and gastroschisis. With
      increasing survival of preterm infants there is an increase in incidence.
      Management is dependent on the use of parenteral nutrition to maintain fluid and
      electrolyte homeostasis and promote growth and development with the longer term
      aim being to promote intestinal adaptation to achieve partial or complete enteral
      autonomy. In this review we discuss the incidence, aetiology, pathophysiology,
      medical and surgical treatments and outcome. 

PMID- 24125823
TI  - The identification of specific disease entities has inspired more research in
      paediatric respiratory medicine.

PMID- 24125824
TI  - In response to: Martinez-Velilla N. GesEPOC guidelines and elderly patients.

PMID- 24125825
TI  - Foreign-body pulmonary embolism.

PMID- 24125826
TI  - Endobronchial ultrasound guided needle sampling without aspiration: and the cell
      block?

PMID- 24125827
TI  - Hydropneumothorax in a patient with bullous emphysema.

PMID- 24125828
TI  - beta-Catenin and cyclin D1 expression in Gli1-independent basal cell carcinomas.

PMID- 24125829
TI  - Reply: One-step nucleic acid amplification assay also predicts axillary lymph
      node status in breast cancer patients: further molecular diagnostic evidence.

PMID- 24125830
TI  - Respiratory virus detection in nasopharyngeal aspirate versus bronchoalveolar
      lavage is dependent on virus type in children with chronic respiratory symptoms.
AB  - BACKGROUND: The comparative yield of respiratory virus detection from
      nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain.
      Furthermore, the significance of virus detection and its relationship to lower
      airway neutrophilic inflammation is poorly studied. OBJECTIVES: To evaluate the
      sensitivity, specificity and predictive values of NPA for detecting respiratory
      viruses in BAL; and to determine the relationship between viruses and lower
      airway neutrophilia in children with non-acute respiratory illness. STUDY DESIGN:
      150 paired NPA and BAL samples were obtained from 75 children aged <18 years
      undergoing flexible bronchoscopy for investigation of chronic respiratory
      symptoms. Viral studies were performed using polymerase chain reaction (PCR).
      Cellularity studies were performed on BALs. Diagnostic parameters of NPA compared
      to BAL and associations between viruses and lower airway %neutrophils were
      evaluated. RESULTS: NPA had a higher yield than BAL for detection of any
      respiratory virus (52 versus 38, respectively). NPA had a high sensitivity (92%)
      and low specificity (57%) for detecting HRV in BAL with poor kappa agreement
      value of 0.398 (95% CI 0.218-0.578, p<0.001). NPA had a fair sensitivity (69%)
      and good specificity (90.3%) for detecting HAdV on BAL, kappa agreement was 0.561
      (95% CI 0.321-0.801, p<0.001). HAdV positivity on NPA, compared to negativity,
      was independently associated with heightened airway neutrophilia [mean difference
      (95% CI): 18 (1,35); p=0.042]. CONCLUSIONS: NPA has a higher yield for
      respiratory virus detection than BAL, however its diagnostic accuracy is
      dependent on viral species. Adenovirus positivity is associated with
      significantly heightened lower airway neutrophilia in children with chronic
      respiratory symptoms.

PMID- 24125831
TI  - New Sicydiinae phylogeny (Teleostei: Gobioidei) inferred from mitochondrial and
      nuclear genes: insights on systematics and ancestral areas.
AB  - The Sicydiinae subfamily (Teleostei: Gobioidei) is the biggest contributor to the
      diversity of fish communities in river systems of tropical islands. These species
      are found in the Indo-Pacific area, the Caribbean region and West Africa. They
      spawn in freshwater, their planktotrophic larvae drift downstream to the sea
      where they develop, before returning to the rivers to grow and reproduce. Hence,
      they are called amphidromous. Their phylogeny has been explored using a total of
      3545 sites from 5 molecular markers (mitochondrial DNA: 16S rDNA, cytochrome
      oxidase I, cytochrome b; nuclear DNA: rhodopsin gene and a nuclear marker
      specially developed for this study, the interferon regulatory factor 2 binding
      protein 1-IRF2PB1). Sequences were obtained for 59 Sicydiinae specimens of 9
      known genera. The Bayesian and maximum likelihood analyses support the monophyly
      of the subfamily as well as the monophylyof all genera except Sicydium, which is
      paraphyletic. Five major clades were identified within this subfamily. One clade
      contained the genus Stiphodon. Another clade contained Sicyopterus, Sicydium and
      Parasicydium with Sicyopterus as sister genus of Sicydium. The non-monophyly of
      Sicydium subclade, because it includes the monotypic genus Parasicydium,
      challenged the validity of Parasicydium genus. Ancestral area reconstruction
      showed that the subfamily emerged in the Central West Pacific region implying
      that previous hypotheses proposing a dispersal route for Sicydiinae into the
      Atlantic Ocean are unsupported by the present analysis. Our results suggest that
      the hypotheses for the dispersal route of the genus Sicydium should be
      reconsidered. 

PMID- 24125832
TI  - Resolving deep lineage divergences in core corvoid passerine birds supports a
      proto-Papuan island origin.
AB  - It is well established that the global expansion of songbirds (Oscines)
      originated in East Gondwana (present day Australo-Papua), and it has been
      postulated that one of the main constituent groups, the "core Corvoidea", with
      more than 750 species, originated in the first islands that emerged where New
      Guinea is now located. However, several polytomous relationships remained within
      the clade, obstructing detailed biogeographical interpretations. This study
      presents a well-resolved family-level phylogeny, based on a dataset of 22 nuclear
      loci and using a suite of partitioning schemes and Maximum Likelihood and
      Bayesian inference methods. Resolving the relationships within the core Corvoidea
      provides evidence for three well-supported main clades, which are in turn sister
      to the New Zealand genus Mohoua. Some monotypic lineages, which have previously
      been considered Incertae sedis, are also placed in a phylogenetic context. The
      well-resolved phylogeny provides a robust framework for biogeographical analyses,
      and provides further support for the hypothesis that core corvoids originated in
      the proto-Papuan island region that emerged north of Australia in the late
      Oligocene/early Miocene. Thus, the core Corvoidea appear to represent a true
      island radiation, which successfully colonized all continents except Antarctica. 

PMID- 24125833
TI  - Effect of defatting on acid hydrolysis rate of maize starch with different
      amylose contents.
AB  - The effect of defatting on the physiochemical properties and the acid hydrolysis
      rate of maize starch with different amylose contents was evaluated in this study.
      The increase in the number of pores and the stripping of starch surface layers
      were observed after defatting by scanning electron microscopy. X-ray diffraction
      spectrum showed that the peaks attributing to the amylose-lipid complex
      disappeared. The relative crystallinity increased by 19% for high-amylose maize
      starch (HMS) on defatting, while the other tested starches virtually unchanged.
      Differential scanning calorimetry study indicated an increase in the thermal
      stability for the defatted starches. Compared with native waxy maize starch, the
      acid hydrolysis rate of the defatted one increased by 6% after 10 days. For
      normal maize starch (NMS) and HMS, the higher rate of hydrolysis was observed
      during the first 5 days. Thereafter, the hydrolysis rate was lower than that of
      their native counterpart. The increase in susceptibility to acid hydrolysis (in
      the first 5 days) was mainly attributed to the defective and porous structures
      formed during defatting process, while the decrease of hydrolysis rate for NMS
      and HMS samples (after the first 5 days) probably resulted from the increase in
      the relative crystallinity. 

PMID- 24125834
TI  - Correlation of ventricular arrhythmias with genotype in arrhythmogenic right
      ventricular cardiomyopathy.
AB  - BACKGROUND: Although mutations of several genes are associated with
      arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation
      between genotype and ventricular arrhythmia features remains unclear. This study
      was aimed to examine the possible association of the 9 known genes of ARVC with
      clinical and electrophysiological characteristics. METHODS AND RESULTS: Ninety
      subjects diagnosed with ARVC who underwent electrophysiological study were
      recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations
      were identified in 57 (63%) subjects. Mutation carriers had more frequent
      clinical ventricular tachycardia (VT; 89% versus 55%; P<0.001) and negative T
      waves in V1 to V3 (61% versus 33%; P=0.016). Subjects with plakophilin-2 (PKP2)
      mutations also had more frequent VT than those without mutations in PKP2.
      Comparison between subjects with multiple and single mutations showed that
      syncope occurred more often in the former group (58% versus 24%; P=0.018). VT was
      significantly more often induced in mutation carriers compared with noncarriers
      (75% versus 39%; P=0.001), as well as in PKP2 mutation carriers compared with
      subjects without PKP2 mutations (80% versus 48%; P=0.002). Induced VT with a rate
      >= 200 bpm was more often documented in mutation carriers (88% versus 54%;
      P=0.013), as well as in PKP2 mutation carriers (91% versus 67%; P=0.041).
      CONCLUSIONS: Pathogenic gene mutations were found in nearly two thirds of
      subjects diagnosed with ARVC. Mutation carriers, especially PKP2, had a higher
      proportion of a history of VT and more inducible fast VT.

PMID- 24125836
TI  - Managers' Perspectives of New Graduates of Accelerated Nursing Programs: How Do
      They Compare with Other Graduates?

PMID- 24125835
TI  - Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant
      and specific anti-cancer agents.
AB  - It is known that flavonoids possess, among others, antioxidant and antitumoral
      properties that depend on their molecular structure. The central objective if
      this study was to investigate the potential antioxidant and antiproliferative
      properties of the flavonol morin and its new oxovanadium(IV) complex (VOmor) that
      was synthesized in order to modify the morin chemical structure. Two osteoblast
      (UMR106 and MC3T3E1), two breast tumor (T47D and SKBR3) and breast epithelial
      cell lines in culture were used for the antitumoral determinations. Additionally,
      a comparative study of their antioxidant capacities using different radicals
      (DPPH, ABTS(+), OH, O2(-), ROO) was performed. Selected mechanisms of action were
      studied using the breast cancer cell lines. Results obtained show that morin and
      its complex behaved as good antioxidant agents for some of the radicals and that
      the complexation improved the behavior with respect to OH and O2(-) radicals
      being morin more effective as ROO scavenger. A considerable variation in
      sensitivity was observed in the breast cancer cells but non-specificity was found
      for the treatment of osteosarcoma. Moreover, the compounds did not affect the
      normal proliferation of the breast epithelial mammal cells. The mechanistic
      studies demonstrated that the complex did not generate reactive oxygen species in
      the cells (confirming the in vitro studies) and did not produce any damage of
      DNA. The plasmatic membrane was observed to be damaged only in the SKBR3 cell
      line. In contrast, the perturbation of the mitochondrial membrane potential and
      the activation of caspase 3/7 for the breast tumor cells revealed an apoptotic
      cell death process. All these results collectively suggested that VOmor complex
      could serve as promising pharmacologically active substance against breast cancer
      treatment. 

PMID- 24125837
TI  - An intelligent approach to nanotechnology.

PMID- 24125838
TI  - CUEDC2 sensitizes chronic myeloid leukemic cells to imatinib treatment.
AB  - CUEDC2, a newly reported protein, has been found to be ubiquitously expressed in
      human tissues and repress NF-kappaB activity. To study the role of CUEDC2 in
      chronic myeloid leukemia (CML), we explored the function of CUEDC2 in CML cells
      through using the CML cell line K562 and its imatinib resistant cells K562/G01.
      K562 cells expressed a relatively higher level of CUEDC2 compared to K562/G01
      cells. Knockdown of CUEDC2 in K562 cells resulted in decreased cell apoptosis
      after imatinib treatment; when CUEDC2 was overexpressed in K562/G01 cells,
      imatinib induced more cell apoptosis. By analyzing the activity of NF-kappaB, the
      results indicated a negative association between the expression of CUEDC2 and NF
      kappaB signaling pathway in these CML cells. Our data suggested that the
      expression level of CUEDC2 has an inverse correlation with imatinib resistance
      and activity of NF-kappaB signaling pathway in CML cells, CUEDC2 could regulate
      imatinib sensitivity in CML cells at least partially through NF-kappaB signaling
      pathway. 

PMID- 24125839
TI  - Steroids, nuclear receptors and breast cancer. Preface.

PMID- 24125840
TI  - Lupinus albus plants acquire mercury tolerance when inoculated with an Hg
      resistant Bradyrhizobium strain.
AB  - One strain of Bradyrhizobium canariense (L-7AH) was selected for its metal
      resistance and ability to nodulate white lupin (Lupinus albus L.) plants, from a
      collection of rhizobial strains previously created from soils of the Almaden
      mining district (Spain) with varying levels of Hg contamination. Plants were
      inoculated with either strain L-7AH (Hg-tolerant) or L-3 (Hg-sensitive, used as
      control), and watered with nutrient solutions supplemented with various
      concentrations (0-200 MUM) of HgCl2 in a growth chamber. L. albus inoculated with
      L-7AH were able to nodulate even at the highest concentration of Hg while those
      inoculated with L-3 had virtually no nodules at Hg concentrations above 25 MUM.
      Plants inoculated with L-7AH, but not those with the control strain, were able to
      accumulate large amounts of Hg in their roots and nodules. Nodulation with L-7AH
      allowed plants to maintain constant levels of both chlorophylls and carotenoids
      in their leaves and a high photosynthetic efficiency, whereas in those inoculated
      with L-3 both pigment content and photosynthetic efficiency decreased
      significantly as Hg concentration increased. Nitrogenase activity of plants
      nodulated with L-7AH remained fairly constant at all concentrations of Hg used.
      Results suggest that this symbiotic pair may be used for rhizoremediation of Hg
      contaminated soils. 

PMID- 24125844
TI  - Associations between fibrocytes and postcontrast myocardial T1 times in
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Fibrocytes are bone marrow-derived mesenchymal progenitors that have
      been linked to various fibrotic disorders. This study was undertaken to
      investigate whether fibrocytes are increased in diffuse myocardial fibrosis in
      humans. METHODS AND RESULTS: Thirty-seven patients with hypertrophic
      cardiomyopathy (HCM) and 20 healthy controls were recruited. Cardiac magnetic
      resonance imaging with postcontrast T1 mapping was performed to non-invasively
      quantify diffuse myocardial fibrosis and these patients were classified into 2
      groups (T1 < 470 ms or T1 >= 470 ms, as likely or unlikely to have diffuse
      fibrosis, respectively). Circulating fibrocytes (CD45+/CD34+/collagen I+) were
      measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were
      cultured for 13 days and fibrocytes were quantitated by flow cytometry
      (CD45+/collagen I+) and real-time PCR (gene expression of matrix proteins).
      Plasma cytokines/chemokines mediating fibrocyte trafficking and differentiation
      were measured by multiplex assays. Circulating fibrocytes were decreased in HCM
      patients compared to controls. The proportion of fibrocytes derived from PBMCs
      was increased in patients with diffuse fibrosis compared with those without or
      controls (31.1 +/- 4.1% versus 18.9 +/- 3.9% and 10.9 +/- 2.0%, P < 0.05 and P <
      0.001, respectively), and the proportion of fibrocytes was inversely correlated
      with T1 time (r = -0.37, P = 0.03). Plasma levels of stromal cell-derived factor
      1 were elevated in patients with diffuse fibrosis compared with those without or
      controls (5131 +/- 271 pg/mL versus 3893 +/- 356 pg/mL and 4172 +/- 185 pg/mL,
      respectively, both P < 0.05). CONCLUSIONS: HCM patients with diffuse fibrosis as
      assessed by postcontrast T1 mapping have elevated plasma SDF and an enhanced
      ability of PBMCs to differentiate into fibrocytes, suggesting that fibrocytes may
      contribute to the pathogenesis of myocardial fibrosis.

PMID- 24125845
TI  - Renal denervation prevents stroke and brain injury via attenuation of oxidative
      stress in hypertensive rats.
AB  - BACKGROUND: Although renal denervation (RD) is shown to reduce blood pressure
      significantly in patients with resistant hypertension, the benefit of RD in
      prevention of stroke is unknown. We hypothesized that RD can prevent the
      incidence of stroke and brain injury in hypertensive rats beyond blood pressure
      lowering. METHODS AND RESULTS: High-salt-loaded, stroke-prone, spontaneously
      hypertensive rats (SHRSP) were divided into 4 groups: (1) control; (2) sham
      operation; (3) bilateral RD; and (4) hydralazine administration to examine the
      effect of RD on stroke and brain injury of SHRSP. RD significantly reduced the
      onset of neurological deficit and death in SHRSP, and this protection against
      stroke by RD was associated with the increase in cerebral blood flow (CBF), the
      suppression of blood-brain barrier disruption, the limitation of white matter
      (WM) lesions, and the attenuation of macrophage infiltration and activated
      microglia. Furthermore, RD significantly attenuated brain oxidative stress, and
      NADPH oxidase subunits, P67 and Rac1 in SHRSP. On the other hand, hydralazine,
      with similar blood pressure lowering to RD, did not significantly suppress the
      onset of stroke and brain injury in SHRSP. Furthermore, RD prevented cardiac
      remodeling and vascular endothelial impairment in SHRSP. CONCLUSIONS: Our present
      work provided the first experimental evidence that RD can prevent hypertensive
      stroke and brain injury, beyond blood pressure lowering, thereby highlighting RD
      as a promising therapeutic strategy for stroke as well as hypertension.

PMID- 24125846
TI  - Comparison of performance achievement award recognition with primary stroke
      center certification for acute ischemic stroke care.
AB  - BACKGROUND: Hospital certification and recognition programs represent 2
      independent but commonly used systems to distinguish hospitals, yet they have not
      been directly compared. This study assessed acute ischemic stroke quality of care
      measure conformity by hospitals receiving Primary Stroke Center (PSC)
      certification and those receiving the American Heart Association's Get With The
      Guidelines-Stroke (GWTG-Stroke) Performance Achievement Award (PAA) recognition.
      METHODS AND RESULTS: The patient and hospital characteristics as well as
      performance/quality measures for acute ischemic stroke from 1356 hospitals
      participating in the GWTG-Stroke Program 2010-2012 were compared. Hospitals were
      classified as PAA+/PSC+ (hospitals n = 410, patients n = 169,302), PAA+/PSC- (n =
      415, n = 129,454), PAA-/PSC+ (n = 88, n = 26,386), and PAA-/PSC- (n = 443, n =
      75,565). A comprehensive set of stroke measures were compared with adjustment for
      patient and hospital characteristics. Patient characteristics were similar by PAA
      and PSC status but PAA-/PSC- hospitals were more likely to be smaller and
      nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC-
      hospitals, intermediate for PAA-/PSC+ hospitals, and lowest for PAA-/PSC-
      hospitals (all-or-none care measure 91.2%, 91.2%, 84.3%, and 76.9%,
      respectively). After adjustment for patient and hospital characteristics,
      PAA+/PSC+, PAA+/PSC-, and PAA-/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47);
      3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all
      indicated stroke performance measures to patients compared with PAA-/PSC-
      hospitals. CONCLUSIONS: While both PSC certification and GWTG-Stroke PAA
      recognition identified hospitals providing higher conformity with care measures
      for patients hospitalized with acute ischemic stroke, PAA recognition was a more
      robust identifier of hospitals with better performance.

PMID- 24125847
TI  - Abnormal calcium cycling and cardiac arrhythmias associated with the human
      Ser96Ala genetic variant of histidine-rich calcium-binding protein.
AB  - BACKGROUND: A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR)
      histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular
      arrhythmia and sudden death in dilated cardiomyopathy. However, the precise
      mechanisms affecting SR function and leading to arrhythmias remain elusive.
      METHODS AND RESULTS: We generated transgenic mice with cardiac-specific
      expression of human Ala96 HRC or Ser96 HRC in the null background to assess
      function in absence of endogenous protein. Ala96 HRC decreased (25% to 30%)
      cardiomyocyte contractility and Ca2+ kinetics compared with Ser96 HRC in the
      absence of any structural or histological abnormalities. Furthermore, the
      frequency of Ca2+ waves was significantly higher (10-fold), although SR Ca2+ load
      was reduced (by 27%) in Ala96 HRC cells. The underlying mechanisms involved
      diminished interaction of Ala96 HRC with triadin, affecting ryanodine receptor
      (RyR) stability. Indeed, the open probability of RyR, assessed by use of
      ryanodine binding, was significantly increased. Accordingly, stress conditions (5
      Hz plus isoproterenol) induced aftercontractions (65% in Ala96 versus 12% in
      Ser96) and delayed afterdepolarizations (70% in Ala96 versus 20% in Ser96). The
      increased SR Ca2+ leak was accompanied by hyperphosphorylation (1.6-fold) of RyR
      at Ser2814 by calmodulin-dependent protein kinase II. Accordingly, inclusion of
      the calmodulin-dependent protein kinase II inhibitor KN93 prevented Ser2814
      phosphorylation and partially reversed the increases in Ca2+ spark frequency and
      wave production. Parallel in vivo studies revealed ventricular ectopy on short
      term isoproterenol challenge and increased (4-fold) propensity to arrhythmias,
      including nonsustained ventricular tachycardia, after myocardial infarction in
      Ala96 HRC mice. CONCLUSIONS: These findings suggest that aberrant SR Ca2+ release
      and increased susceptibility to delayed afterdepolarizations underlie triggered
      arrhythmic activity in human Ala96 HRC carriers.

PMID- 24125848
TI  - Endovascular treatment of bilateral carotid artery pseudoaneurysms after blunt
      carotid injury.
AB  - The detection of blunt carotid artery injures has improved because of more
      aggressive screening protocols. Initial treatment depends on multiple factors;
      however, controversy exists with regard to the treatment of pseudoaneurysmal
      degeneration, especially in this age of endovascular treatment options. Current
      options include anticoagulation, open surgical repair, and endovascular repair.
      We report a rare case of bilateral carotid artery pseudoaneurysm degeneration
      after bilateral carotid artery dissection caused by blunt trauma. 

PMID- 24125849
TI  - Flavones as isosteres of 4(1H)-quinolones: discovery of ligand efficient and dual
      stage antimalarial lead compounds.
AB  - Malaria is responsible for nearly one million deaths annually, and the increasing
      prevalence of multi-resistant strains of Plasmodium falciparum poses a great
      challenge to controlling the disease. A diverse set of flavones, isosteric to
      4(1H)-quinolones, were prepared and profiled for their antiplasmodial activity
      against the blood stage of P. falciparum W2 strain, and the liver stage of the
      rodent parasite Plasmodium berghei. Ligand efficient leads were identified as
      dual stage antimalarials, suggesting that scaffold optimization may afford potent
      antiplasmodial compounds.

PMID- 24125851
TI  - Novel acetamidothiazole derivatives: synthesis and in vitro anticancer
      evaluation.
AB  - A novel series of acetamide derivatives possessing both 2-imino-4-arylthiazoles
      and morpholine or different piperazines were synthesized and characterized by IR,
      (1)H NMR, (13)C NMR, elemental and mass spectral analyses. Twelve compounds were
      granted NSC codes at National Cancer Institute (NCI), USA for anticancer activity
      at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the compounds
      tested, compounds 5a and 6b were found to be the most active candidates of the
      synthesized series. Assessment of toxicities, druglikeness, and drug score
      profiles of compounds 5a and 6b are promising. Some of the synthesized compounds
      showed a good docking score with potential anticancer targets, chosen based on
      pharmacophore mapping of the established derivatives.

PMID- 24125850
TI  - Mastering tricyclic ring systems for desirable functional cannabinoid activity.
AB  - There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the
      treatment of neuropathic pain and other indications. In continuation of our
      ongoing program aiming for the development of new small molecule cannabinoid
      ligands, we have synthesized a novel series of carbazole and gamma-carboline
      derivatives. The affinities of the newly synthesized compounds were determined by
      a competitive radioligand displacement assay for human CB2 cannabinoid receptor
      and rat CB1 cannabinoid receptor. Functional activity and selectivity at human
      CB1 and CB2 receptors were characterized using receptor internalization and
      [(35)S]GTP-gamma-S assays. The structure-activity relationship and optimization
      studies of the carbazole series have led to the discovery of a non-selective CB1
      and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2
      selectivity of this lead compound have led to the discovery of CB2 selective
      compound 64, which robustly internalized CB2 receptors. Compound 64 had potent
      inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain.
      Other potent and CB2 receptor-selective compounds, including compounds 63 and 68,
      and a selective CB1 agonist, compound 74 were also discovered. In addition, we
      identified the CB2 ligand 35 which failed to promote CB2 receptor internalization
      and inhibited compound CP55,940-induced CB2 internalization despite a high CB2
      receptor affinity. The present study provides novel tricyclic series as a
      starting point for further investigations of CB2 pharmacology and pain treatment.

PMID- 24125852
TI  - The post-thaw irradiation of avian spermatozoa with He-Ne laser differently
      affects chicken, pheasant and turkey sperm quality.
AB  - The effects of post-thaw Helium-Neon (He-Ne) laser irradiation on mobility and
      functional integrity of frozen/thawed chicken, pheasant and turkey spermatozoa
      were investigated. Cytochrome C oxidase (COX) activity was also determined as a
      measure of the effect of irradiation on mitochondrial bioenergetics. Semen
      samples from each species were collected, processed and frozen according to the
      pellet procedure. After thawing, each semen sample was divided into two
      subsamples: the first one was the control; the second one was irradiated with a
      single mode continuous He-Ne laser wave (wavelength 632.8 nm; 6 mW; 3.96
      J/cm(2)). Then the samples were assessed for sperm mobility (Accudenz((r)) swim
      down test), viability (SYBR-14/PI staining), osmotic-resistance (HOS test) and
      COX activity. The irradiation was effective P<0.05 increasing sperm motility in
      the turkey semen (0.228 +/- 0.01 compared with 0.294 +/- 0.02). The irradiation
      also caused an increase (P<0.05) of the COX activity in pheasant (+135 +/- 4%)
      and turkey (+116 +/- 4%) sperm, without affecting viability and osmotic
      resistance. The COX was positively correlated (P<0.05) with the viability of
      chicken sperm, however no significant interactions were found between mobility
      and COX activity in the three avian species. Due to the difference in energetic
      metabolism among avian species used in this study, the He-Ne laser irradiation
      has a differential action on bio-stimulation of turkey, chicken and pheasant
      spermatozoa. The present results are the first to elucidate the possibility for
      restoration of motility of cryopreserved avian spermatozoa by bio-stimulation
      provided via He-Ne laser irradiation.

PMID- 24125853
TI  - Impact of seminal plasma superoxide dismutase and glutathione peroxidase on
      cryopreserved buffalo spermatozoa.
AB  - Fifty semen samples were collected from sixteen buffalo-bulls (4-10 years old)
      and evaluated before cryopreservation. The activity of superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) as well
      as the levels of glutathione (GSH) and malondialdehyde (MDA) were assayed in the
      seminal plasma before freezing. Aspartate aminotransferase (AST) activity and
      cholesterol content were assayed in seminal plasma before freezing and after
      thawing. Results revealed the presence of SOD and GPx activities (0.07 +/- 0.01
      U/ml and 14.59 +/- 0.50 nmol/min/ml, respectively) in buffaloes' seminal plasma.
      SOD activity was positively correlated with both of GSH level and GST activity in
      seminal plasma, and showed an inverse relationship with both cholesterol efflux
      and post-thaw abnormal tails of buffalo spermatozoa. A positive correlation was
      found between GPx activity in seminal plasma and abnormal tails and an inverse
      relationship with both post-thaw viability indices and increased motility in
      response to PTx. GST activity showed a positive correlation with the increased
      motility after addition of PTx and negative correlations with both of cholesterol
      level and AST activity. MDA levels were negatively correlated with motility after
      addition of PTx and positive correlations with both post-thaw abnormal acrosomes
      and tails. Buffalo seminal plasma contains high activities of SOD, GPx and GST
      enzymes and GSH levels that have an influence on the functional competence of
      cryopreserved spermatozoa.

PMID- 24125854
TI  - EEG and electrodermal activity in girls with Attention-Deficit/Hyperactivity
      Disorder.
AB  - OBJECTIVE: This study investigated the Hypoarousal Model of Attention
      Deficit/Hyperactivity Disorder (AD/HD) in girls. METHODS: 40 girls with AD/HD and
      40 girl controls (aged 7-12 years) had an eyes-closed resting EEG recorded from
      19 electrodes and Fourier transformed. Estimates for total power, absolute and
      relative power in the delta, theta, alpha, beta and gamma frequency bands, and
      theta/beta ratio were analysed in nine cortical regions. Skin conductance level
      (SCL) was simultaneously recorded. Regression analyses explored relationships
      between symptoms and physiology. RESULTS: Compared with controls, girls with
      AD/HD had globally elevated relative delta, globally reduced absolute beta, and
      globally reduced absolute and relative gamma activity. Girls with AD/HD also had
      lower mean SCL. Inattentive symptoms were predicted by elevated frontal relative
      delta, reduced SCL, and reduced temporal relative gamma activity, while elevated
      hyperactive-impulsive symptoms correlated with elevated frontal relative delta
      activity in both the patient and control groups. CONCLUSIONS: These EEG results
      are comparable with the limited female AD/HD literature. Girls with AD/HD are
      hypoaroused, indicated by reduced SCL, and appear to have an anomalous arousal
      mechanism. Absolute and relative gamma results are similar to previous findings
      in AD/HD children. Symptom correlations with physiology offer intriguing insights
      for future research. SIGNIFICANCE: This is the first study to examine CNS arousal
      exclusively in girls with AD/HD.

PMID- 24125855
TI  - The exhaustibility of Lambert-Eaton myasthenic syndrome.

PMID- 24125856
TI  - Decreased sleep spindle density in patients with idiopathic REM sleep behavior
      disorder and patients with Parkinson's disease.
AB  - OBJECTIVE: To determine whether sleep spindles (SS) are potentially a biomarker
      for Parkinson's disease (PD). METHODS: Fifteen PD patients with REM sleep
      behavior disorder (PD+RBD), 15 PD patients without RBD (PD-RBD), 15 idiopathic
      RBD (iRBD) patients and 15 age-matched controls underwent polysomnography (PSG).
      SS were scored in an extract of data from control subjects. An automatic SS
      detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine
      (SVM) was developed and applied to the PSG recordings. The SS densities in N1,
      N2, N3, all NREM combined and REM sleep were obtained and evaluated across the
      groups. RESULTS: The SS detector achieved a sensitivity of 84.7% and a
      specificity of 84.5%. At a significance level of alpha=1%, the iRBD and PD+RBD
      patients had a significantly lower SS density than the control group in N2, N3
      and all NREM stages combined. At a significance level of alpha=5%, PD-RBD had a
      significantly lower SS density in N2 and all NREM stages combined. CONCLUSIONS:
      The lower SS density suggests involvement in pre-thalamic fibers involved in SS
      generation. SS density is a potential early PD biomarker. SIGNIFICANCE: It is
      likely that an automatic SS detector could be a supportive diagnostic tool in the
      evaluation of iRBD and PD patients.

PMID- 24125857
TI  - EEG-neurofeedback for optimising performance. I: a review of cognitive and
      affective outcome in healthy participants.
AB  - A re-emergence of research on EEG-neurofeedback followed controlled evidence of
      clinical benefits and validation of cognitive/affective gains in healthy
      participants including correlations in support of feedback learning mediating
      outcome. Controlled studies with healthy and elderly participants, which have
      increased exponentially, are reviewed including protocols from the clinic:
      sensory-motor rhythm, beta1 and alpha/theta ratios, down-training theta maxima,
      and from neuroscience: upper-alpha, theta, gamma, alpha desynchronisation.
      Outcome gains include sustained attention, orienting and executive attention, the
      P300b, memory, spatial rotation, RT, complex psychomotor skills, implicit
      procedural memory, recognition memory, perceptual binding, intelligence, mood and
      well-being. Twenty-three of the controlled studies report neurofeedback learning
      indices along with beneficial outcomes, of which eight report correlations in
      support of a meditation link, results which will be supplemented by further
      creativity and the performing arts evidence in Part II. Validity evidence from
      optimal performance studies represents an advance for the neurofeedback field
      demonstrating that cross fertilisation between clinical and optimal performance
      domains will be fruitful. Theoretical and methodological issues are outlined
      further in Part III. 

PMID- 24125859
TI  - Acneiform eruption in a 5-year-old due to vitamin B12 supplementation.

PMID- 24125860
TI  - Peroxiredoxin 2 knockdown by RNA interference inhibits the growth of colorectal
      cancer cells by downregulating Wnt/beta-catenin signaling.
AB  - Peroxiredoxin 2 (Prdx2) has been shown to act as an antioxidant whose main
      function is to reduce hydrogen peroxide (H2O2) in cells, and Prdx2 is abnormally
      elevated in colorectal cancer (CRC). However, the functional significance of this
      up-regulation and the detailed molecular mechanism behind the regulatory effect
      of Prdx2 on the growth of CRC cells have not been elucidated. In this study, we
      demonstrated that Prdx2 knockdown using a lentiviral vector-mediated specific
      shRNA inhibited cell growth, stimulated apoptosis, and augmented the production
      of endogenous reactive oxygen species (ROS). Further, silencing of Prdx2 resulted
      in an altered expression of proteins associated with the Wnt signaling pathway.
      Finally, Prdx2 knockdown contributed to attenuated CRC growth in BALB/c nude
      mice. In conclusion, these findings demonstrate that the regulatory effects of
      Prdx2 can be partially attributed to Wnt/beta-catenin signaling. 

PMID- 24125858
TI  - Auditory verbal hallucinations as atypical inner speech monitoring, and the
      potential of neurostimulation as a treatment option.
AB  - Auditory verbal hallucinations (AVHs) are the experience of hearing voices in the
      absence of any speaker, often associated with a schizophrenia diagnosis.
      Prominent cognitive models of AVHs suggest they may be the result of inner speech
      being misattributed to an external or non-self source, due to atypical self- or
      reality monitoring. These arguments are supported by studies showing that people
      experiencing AVHs often show an externalising bias during monitoring tasks, and
      neuroimaging evidence which implicates superior temporal brain regions, both
      during AVHs and during tasks that measure verbal self-monitoring performance.
      Recently, efficacy of noninvasive neurostimulation techniques as a treatment
      option for AVHs has been tested. Meta-analyses show a moderate effect size in
      reduction of AVH frequency, but there has been little attempt to explain the
      therapeutic effect of neurostimulation in relation to existing cognitive models.
      This article reviews inner speech models of AVHs, and argues that a possible
      explanation for reduction in frequency following treatment may be modulation of
      activity in the brain regions involving the monitoring of inner speech. 

PMID- 24125861
TI  - Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via
      PI3K/Akt/mTOR signaling pathway.
AB  - Autophagy plays an important role in cellular homeostasis through the disposal
      and recycling of cellular components. Cancer stem cells (CSCs) play major roles
      in cancer initiation, progression, and drug resistance. Rottlerin (Rott) is an
      active molecule isolated from Mallotus philippinensis, a medicinal plant used in
      Ayurvedic Medicine for anti-allergic and anti-helminthic treatments, demonstrates
      anticancer activities. However, the molecular mechanisms by which it induces
      autophagy in prostate CSCs have not been examined. The main objective of the
      paper was to examine the molecular mechanisms by which Rott induces autophagy in
      prostate CSCs. Autophagy was measured by the lipid modification of light chain-3
      (LC3) and the formation of autophagosomes. Apoptosis was measured by flow
      cytometer analysis. The Western blot analysis was used to examine the effects of
      Rott on the expression of PI3K, phosphorylation of Akt, phosphorylation of mTOR,
      and phosphorylation of AMPK in pros CSCs. RNAi technology was used to inhibit the
      expression of Beclin-1 and ATG-7. Rott induced the lipid modification of light
      chain-3 (LC3) and the formation of autophagosomes after 24h of Rott treatment in
      prostate CSCs. Rott-treated prostate CSCs induced transition from LC3-I to LC3
      II, a hall mark of autophagy. Rott also induced the expression of Atg5, Atg7,
      Atg12 and Beclin-1 proteins during autophagy. The knock-down of Atg7 and Beclin-1
      blocked Rott-induced autophagy. Furthermore, Rott induced AMPK phosphorylation
      was blocked by 3-MA, Baf and CHX. In addition, inhibition of AMPK expression by
      shRNA blocked Rott induced autophagy. In conclusion, a better understanding of
      the biology of autophagy and the pharmacology of autophagy modulators has the
      potential for facilitating the development of autophagy-based therapeutic
      interventions for prostate cancer. 

PMID- 24125863
TI  - Abscopal effects of radiation therapy: a clinical review for the radiobiologist.
AB  - An "abscopal" effect occurs when localized irradiation perturbs the organism as a
      whole, with consequences that can be either beneficial or detrimental.
      Mechanistic explanations of this effect are challenging. From the oncologist's
      perspective, the term refers to distant tumor regression after localized
      irradiation. On the other hand, from a biologist's point of view, abscopal
      effects include induction of genomic instability, cell death, and oncogenic
      transformation in normal tissues. This conceptual dichotomy is explored in this
      review, with a focus on clinically documented cases of anti-tumor abscopal
      effects and abscopal effects in normal tissues. This review also outlines several
      suggested mechanisms for abscopal effects. 

PMID- 24125864
TI  - Determinants of low referral rates for ophthalmologic examination in people with
      type 2 diabetes in Hungary.
AB  - GPs' and patients' socio-demographic characteristics were investigated as
      possible, determinants of ophthalmologic examination referral rates among type 2
      diabetes mellitus patients. Female GPs were more effective among retinopathy-free
      patients, while male GPs among patients with retinopathy. It could be explained
      by the gender related authority-empathy balance, manifested, through
      communication style.

PMID- 24125862
TI  - Epigenetics and cancer metabolism.
AB  - Cancer cells adapt their metabolism to support proliferation and survival. A
      hallmark of cancer, this alteration is characterized by dysfunctional metabolic
      enzymes, changes in nutrient availability, tumor microenvironment and oncogenic
      mutations. Metabolic rewiring in cancer is tightly connected to changes at the
      epigenetic level. Enzymes that mediate epigenetic status of cells catalyze
      posttranslational modifications of DNA and histones and influence metabolic gene
      expression. These enzymes require metabolites that are used as cofactors and
      substrates to carry out reactions. This interaction of epigenetics and metabolism
      constitutes a new avenue of cancer biology and could lead to new insights for the
      development of anti-cancer therapeutics. 

PMID- 24125865
TI  - Deliverable navigation for multicriteria IMRT treatment planning by combining
      shared and individual apertures.
AB  - We consider the problem of deliverable Pareto surface navigation for step-and
      shoot intensity-modulated radiation therapy. This problem amounts to calculation
      of a collection of treatment plans with the property that convex combinations of
      plans are directly deliverable. Previous methods for deliverable navigation
      impose restrictions on the number of apertures of the individual plans, or
      require that all treatment plans have identical apertures. We introduce
      simultaneous direct step-and-shoot optimization of multiple plans subject to
      constraints that some of the apertures must be identical across all plans. This
      method generalizes previous methods for deliverable navigation to allow for
      treatment plans with some apertures from a collective pool and some apertures
      that are individual. The method can also be used as a post-processing step to
      previous methods for deliverable navigation in order to improve upon their plans.
      By applying the method to subsets of plans in the collection representing the
      Pareto set, we show how it can enable convergence toward the unrestricted (non
      navigable) Pareto set where all apertures are individual. 

PMID- 24125866
TI  - Influence of pH on the survival of Dictyosphaerium chlorelloides populations
      living in aquatic environments highly contaminated with chromium.
AB  - The accommodation of photosynthetic organisms to adverse conditions, such as pH
      changes in the aquatic environment, and their response to aquatic pollutants is
      essential to develop future biosensors. The present study reports the ability of
      both Cr(VI)-sensitive and tolerant Dyctiosphaerium chlorelloides strains to live
      in aqueous solutions highly contaminated with hexavalent chromium under varying
      ranges of pH, by the determination of chromium toxic effects on these strains.
      Studies of cell growth, photosynthetic quantum yield and gross photosynthesis
      rate show that both D. chlorelloides strains are able to survive in alkaline and
      moderately acidified (pH 4.25) aquatic environments. Below this pH value cell
      populations from both strains exposed for short periods of time to Cr(VI) showed
      alterations in the three parameters studied. There were no significant
      differences comparing the response of both strains at pH change in the culture
      medium. However, Cr(VI)-tolerant strain exhibits a better fit to maintain cell
      growth than Cr(VI)-sensitive strain when both were subjected to pH 4.25 in the
      culture medium. The absence of significant differences in photosynthetic activity
      results for both strains suggests that the lower sensitivity exhibited by Cr(VI)
      tolerant strain would be due to cellular morphological changes rather than
      changes in cellular activity. 

PMID- 24125867
TI  - Organochlorine pesticides in fish from Taihu Lake, China, and associated human
      health risk assessment.
AB  - Because contaminants and nutrients always coexist in fish, the risk from
      contaminants and the benefit from nutrients, such as eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) are also concomitant via fish consumption. To
      investigate the risk and benefit via fish consumption, concentrations of
      dichlorodiphenyltrichloroethane and its metabolites (DDTs), and
      hexachlorocyclohexanes (HCHs) in the whole- and portion-muscles of fish from
      Taihu Lake, China, were measured. Based on the contaminant data and nutrients
      from our previous study, and the associated risk and benefit via fish consumption
      were estimated. The concentrations of DDTs and HCHs in the whole-muscles ranged
      from 7.8 * 102 to 3.4*103 pg g-1 ww, and from 67.3 to 300 pg g-1 ww,
      respectively. Of DDTs and HCHs measured, p,p'-DDE and beta-HCH were respectively
      the most abundant pesticides. The composition profiles of DDTs and HCHs suggested
      that the pesticides were mainly historical residues. The benefit-risk quotient
      (BRQ) of EPA+DHA vs. POPs (persistent organic pollutants including data of DDTs,
      HCHs, and those of polychlorinated biphenyls and polybrominated diphenyl ethers
      cited from our previous study) via consumption of fish from Taihu Lake was
      calculated. As a result, to achieve the recommended EPA+DHA intake of 250 mg d-1
      for a healthy adult, the consumption of most fish species from the lake can cause
      cancer and non-cancer risks. However, the fish consumption at the rates of 44.9 g
      d-1 by Chinese would not lead to the risks for most of the species. The results
      also suggested that the risk of consuming silver carp was generally lower than
      other fish species, and those of dorsal muscles were lower than ventral and tail
      muscles.

PMID- 24125868
TI  - Signal regulation involved in sulfur dioxide-induced guard cell apoptosis in
      Hemerocallis fulva.
AB  - Chronic and acute exposure to SO2 is associated with increased risks of various
      damages to plants. In the present study, epidermal strip experiment was employed
      to investigate SO2-induced guard cells apoptosis and the signal regulation in
      Hemerocallis fulva. The results showed that with the increase of treatment
      concentrate of SO2 derivates (a mixture of sodium sulfite and sodium bisulfite,
      3:1, mmol L-1/mmol L-1, 1.0-5.0 mmol L-1), the physiological activity of the
      guard cells declined and cell death occurred. While the concentration of SO2
      derivatives exceeded 2.0 mmol L-1, the percentage of cell death increased
      significantly (P<0.05). Typical features of apoptosis including nuclear
      condensation, nuclear elongation, fragmentation etc. were found. Meanwhile,
      concomitant presence of nitric oxide (NO), reactive oxygen species (ROS) and Ca2+
      level increment appeared. However, SO2-induced cell death can be effectively
      blocked by either of the following substances with their respective optimal
      concentrations: antioxidant ascorbic acid (Asc; 0.05 mmol L-1) or catalase (CAT;
      200 U mL-1), nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-
      tetramethylmidiazoline-1-oxyl-3-oxide (c-PTIO; 0.20 mmol L-1), nitrate reductase
      inhibitor NaN3 (0.20 mmol L-1), Ca2+ chelating agent EGTA (0.05 mmol L-1) or
      plasma membrane Ca2+ channel blocker LaCl3 (0.05 mmol L-1). In addition to a
      significant decrease in cell death rate, a reduction in the levels of reactive
      oxygen species (ROS), NO and Ca2+ was observed. Further study showed that
      compared to treatment with SO2 alone, Asc treatment led to a decrease in NO and
      Ca2+ levels and NaN3 treatment led to a decrease in ROS and Ca2+ levels, but the
      NO and ROS levels of the LaCl3 treatment changed little. All results suggested
      that NO, ROS and Ca2+ were involved in the apoptosis induced by SO2 in H. fulva.
      The process might be related to the burst of NO or ROS, which would activate the
      plasma Ca2+ channel and result in the increase of intercellular Ca2+.

PMID- 24125869
TI  - An ecotoxicological study on tin- and bismuth-catalysed PDMS based coatings
      containing a surface-active polymer.
AB  - Novel films were prepared by condensation curing reaction of a poly(dimethyl
      siloxane) (PDMS) matrix with bismuth neodecanoate and dibutyltin diacetate
      catalysts. An ecotoxicological study was performed on the leachates of the
      coatings using the bacterium Vibrio fischeri, the unicellular alga Dunaliella
      tertiolecta, the crustacean Artemia salina and the fish Sparus aurata (larvae) as
      testing organisms. A copper-based self-polishing commercial paint was also tested
      as reference. The results showed that the tin-catalysed coatings and the copper
      paint were highly toxic against at least two of the four test organisms, whereas
      bismuth-catalysed coatings did not show any toxic effect. Moreover, the same
      biological assessment was also carried out on PDMS coatings containing a surface
      active fluorinated polymer. The toxicity of the entire polymeric system resulted
      only from the tin catalyst used for the condensation curing reaction, as the
      bismuth catalysed coatings incorporating the surface-active polymer remained
      atoxic toward all the tested organisms. 

PMID- 24125870
TI  - Cytotoxic effects of Reactive Blue 33 on Allium cepa determined using Taguchi's
      L8 orthogonal array.
AB  - In this study, Taguchi L8 experimental design was applied to determine cytotoxic
      effects of Reactive Blue 33, which is the most toxic azo reactive dye species, on
      Allium cepa. With this aim, A. cepa test system was performed to achieve targeted
      experimental design with three factors (concentration of dye, pH and volume) in
      two different levels. Toxic conditions were determined considering calculated
      signal-to-noise ratios. "Smaller is better" approach was followed to calculate
      signal-to-noise ratios as it was aimed to obtain lower root lengths. In the work,
      toxic effects of azo dye were also predicted by using the Taguchi method. Taguchi
      model showed that experimental and predicted values were closer to each other
      demonstrating the success of Taguchi approach.

PMID- 24125871
TI  - Impacts of Cu(II) on the kinetics of nitrogen removal during the wastewater
      treatment process.
AB  - The effects of Cu(II) on the substrate removal kinetics, including the COD, NH4+
      N, and NO(x)--N removal, were investigated by batch assays. Results showed that
      Cu(II) loading concentration of 10 mg/L significantly inhibited both the organic
      substrate removal efficiency and its specific removal rate, and the inhibitory
      rate was higher in the nitrification process than in the denitrification process.
      The removal efficiency and the specific uptake rate of NH4+-N would be
      significantly inhibited by the Cu(II) loading concentration of 10 mg/L. As for
      the denitrificantion process, the feeding concentration of Cu(II) no more than 20
      mg/L posed no significant inhibitory effect on the final removal efficiencies of
      NO(x)--N, however, 5 mg/L Cu(II) addition would inhibit the specific nitrogen
      oxides uptake rate by 32.43%. The same Cu(II) loading concentrations caused much
      higher inhibitory rate to the specific uptake rate of the NH4+-N than to that of
      the NO(x)--N. Additionally, the relationships between the Cu(II) loading
      concentrations and their inhibitory rates to the specific removal rate of COD,
      NH4+-N, and NO(x)--N could all be well described by regression equations.

PMID- 24125872
TI  - Do we really want to REACH out to in vitro?
AB  - To comply with international regulations on chemicals, such as REACH
      (registration, evaluation, and authorization of chemicals), an enormous amount of
      toxicity testing is required. Traditional tests will fall short, since these
      strongly rely on in vivo studies, in particular for neurotoxicity. Therefore, a
      shift to alternative/in vitro toxicity testing is essential, in particular for
      neurotoxicity testing. However, the use of in vitro models and in vitro endpoints
      appears far from well accepted. This brief personal view highlights some of the
      concerns regarding in vitro research, e.g. using clonal cell lines such as PC12
      cells and SH-SY5Y cells, to illustrate that many of these concerns may not be
      justified. A better characterization of specific in vitro models as well as a
      better understanding of the motive for using these in vitro models for
      neurotoxicity testing in the scientific community is necessary. The future of
      neurotoxicity testing will involve an increased use of in vitro experiments that
      are carefully designed with respect to compatibility of the exposure paradigm,
      the in vitro model and the chosen endpoint(s). 

PMID- 24125873
TI  - Bone marrow leukaemic transformation of myelodysplastic syndrome revealed by a
      cutaneous Langerhans cell infiltrate: partial response to azacitidine.

PMID- 24125874
TI  - Merkel cell carcinoma of the hand and upper extremity: current trends and
      outcomes.
AB  - Merkel cell carcinomas represent an uncommon yet aggressive skin cancer. We
      sought to identify changes in incidence and predictors of outcomes and survival
      of patients with Merkel cell carcinomas of the hand and upper extremity. The
      Surveillance, Epidemiology and End Results database was used to identify all
      patients with Merkel cell carcinomas of the skin located specifically in the hand
      and upper extremity. Overall, 5211 cases were identified in the period from 1986
      through 2009. The age-adjusted incidence of Merkel cell carcinoma of the hand and
      upper extremity increased from 0.02 cases per 100,000 in 1986 to 0.14 cases per
      100,000 in 2009. The mean age of these patients was 75 years and positive
      regional lymph nodes were identified in 33%. Rate of metastasis was 4.1%. Overall
      survival for the study cohort was 49%. Multivariate analysis identified tumor
      size >5 cm, positive regional lymph nodes and metastasis at diagnosis as
      independent predictors of mortality. The incidence of Merkel cell carcinomas has
      increased substantially over the study period. Overall survival for Merkel cell
      carcinomas of the body and hand and upper extremity is related to tumor size and
      extent of disease at time of clinical presentation. Merkel cell carcinomas of the
      hand and upper extremity tend to be diagnosed at an earlier stage with lower
      rates of regional and systemic spread, and subsequently have a higher overall
      survival rate.

PMID- 24125875
TI  - Changes in three-dimensional speckle-tracking-derived myocardial strain during
      percutaneous coronary intervention.
AB  - BACKGROUND: The aim of this study was to evaluate changes in three-dimensional
      (3D) speckle-tracking-derived myocardial strain during ischemia. METHODS: Twenty
      patients referred for percutaneous coronary intervention were studied (mean age,
      65 +/- 11 years; mean left ventricular ejection fraction, 56 +/- 7%). Of the 20
      study patients, 12 had severe left anterior descending coronary artery stenosis.
      A full-volume apical view using multibeat 3D modality and two-dimensional (2D)
      apical views (four chamber, two chamber, and three chamber) were recorded during
      coronary occlusion before wall motion abnormalities. After percutaneous coronary
      intervention, ultrasound contrast agent was selectively delivered through the
      target lesion to delineate ischemic and peri-ischemic segments (ischemia-adjacent
      segments). Strain values derived from 2D and 3D speckle-tracking echocardiography
      were compared in ischemic and nonischemic segments. RESULTS: Despite no changes
      in wall motion and 2D left ventricular ejection fraction (56 +/- 7% vs 56 +/-
      7%), global longitudinal strain by 2D imaging was impaired during percutaneous
      coronary intervention (-16 +/- 3% vs -14 +/- 3%, P = .01). Similar changes were
      observed for all 3D strain components: -11 +/- 16% for longitudinal (-15 +/- 4%
      vs -13 +/- 4%, P = .03), -13 +/- 25% for circumferential (-15 +/- 4% vs -12 +/-
      4%, P = .02), -12 +/- 16% for area (-25 +/- 5% vs -22 +/- 6%, P = .009), and -12
      +/- 25% for radial global strain (39 +/- 12% vs 33 +/- 12%, P = .04). During
      coronary occlusion, 2D longitudinal peak strain and all 3D peak strain components
      decreased in ischemic segments, while no changes was observed in nonischemic
      segments. In peri-ischemic segments, only 3D longitudinal and area strain were
      impaired during ischemia. CONCLUSIONS: Changes in myocardial deformation related
      to ischemia can be characterized by 3D speckle-tracking echocardiography before
      the stage of wall motion abnormality.

PMID- 24125876
TI  - Systolic and diastolic function assessment in fabry disease patients using
      speckle-tracking imaging and comparison with conventional echocardiographic
      measurements.
AB  - BACKGROUND: Fabry cardiomyopathy is characterized by progressive left ventricular
      hypertrophy (LVH) associated with diastolic dysfunction and is the most common
      cause of death in Fabry disease (FD). However, LVH is not present in all
      subjects, particularly early in disease progression and in female patients.
      Direct assessment of myocardial deformation by strain and strain rate (SR)
      analysis may be sensitive to detect subclinical Fabry cardiomyopathy independent
      of the presence of LVH. METHODS: Systolic (longitudinal, circumferential, and
      radial systolic strain and SR) and diastolic (SR during isovolumic relaxation
      [SR(IVR)] and early diastole and strain at peak transmitral E wave) function was
      assessed in 16 patients with FD using two-dimensional speckle-tracking
      echocardiography. In addition, mean S' and E' mitral annular velocities by
      Doppler tissue imaging were measured. Diastolic filling indices, including
      E/SR(IVR) and E/E' ratios, were calculated. The patients were compared with 24
      healthy age-matched and gender-matched controls. RESULTS: All 16 patients with FD
      had normal left ventricular ejection fractions, and nine patients had LVH.
      Compared with controls, patients with FD had reduced longitudinal systolic strain
      (P < .001) and systolic SR (P = .007), while there were no differences in
      circumferential systolic strain and S'. Diastolic function assessment showed
      reduced longitudinal early diastolic SR (P = .001), SR(IVR) (P < .001), and
      E/SR(IVR) (P < .001), while radial and circumferential diastolic function was not
      affected. Of the conventional diastolic function indices, reductions were seen in
      E (P = .006), E' (P = .021), and E/E' ratio (P < .001). After correcting for LVH,
      only SR(IVR) (P < .001) and E/SR(IVR) (P = .025) remained significantly different
      between patients with FD and controls, with sensitivity of 94% and specificity of
      92% for SR(IVR) of 0.235 sec(-1) (area under the receiver operating
      characteristic curve, 0.953). CONCLUSIONS: Strain and SR analysis is useful in
      identifying patients with FD with reduced myocardial function, with longitudinal
      systolic strain and diastolic isovolumic SR being superior to the other
      echocardiographic measurements of myocardial contraction and relaxation and
      independent of LVH.

PMID- 24125877
TI  - Synthesis and evaluation of N-acylamino acids derivatives of triazenes.
      Activation by tyrosinase in human melanoma cell lines.
AB  - In this research work we report the synthesis of a new series of triazene
      prodrugs designed for Melanocyte-Directed Enzyme Prodrug Therapy (MDEPT). These
      compounds are derived from the N-acyltyrosine amino acid - a good enzyme
      substrate for the tyrosinase enzyme, which is significantly overexpressed in
      melanoma cells. We analysed their chemical stability and plasma enzymatic
      hydrolysis, and we also evaluated the release of the antitumoral drug in the
      presence of the tyrosinase. Subsequently, we performed the evaluation of the
      prodrug cytotoxicity in melanoma cell lines with different levels of tyrosinase
      activity. Prodrug 5c showed the highest cytotoxicity against melanoma cell lines,
      and this effect correlated well with the tyrosinase activity suggesting that
      prodrug cytotoxicity is tyrosinase-dependent. 

PMID- 24125878
TI  - Free thyroxine and thyroid-stimulating hormone reference intervals in very low
      birth weight infants at 3-6 weeks of life with the Beckman Coulter Unicel DxI
      800.
AB  - OBJECTIVES: To establish reference intervals for thyroid stimulating hormone
      (TSH) and free thyroxine (FT4) at 3-6 weeks of age in very low birth weight
      (VLBW) infants with the Beckman Coulter Unicel DxI 800 by gender, birth weight
      (BW) and gestational age (GA) subgroups. DESIGN AND METHODS: A 4 year
      retrospective cohort of 308 VLBW infants (GA=27.9 weeks, BW=992.3g) was studied.
      All blood samples for TSH and FT4 were analyzed using the modified fTSH2 (TSH)
      and two-step competitive enzyme immunoassay (FT4). Reference intervals were
      evaluated according to the most recent Clinical and Laboratory Standards
      Institute (CLSI) guidelines. RESULTS: The study provides non-parametric 95%
      reference intervals with associated 90% confidence intervals for FT4 and TSH
      derived from 308 infants screened at a median of 31 days. The reference intervals
      for this population are TSH=1.14-11.04 mIU/L and FT4=10.9-21.4 pmol/L. TSH
      statistically differed according to birth weight (<1000 g vs 1000-1499 g) while
      FT4 differed according to gender and gestational age at time of testing (<32
      weeks vs >= 32 weeks); however, these differences were not clinically significant
      and a single reference interval for each analyte is reported. CONCLUSION: The
      results of this study highlight the importance and complexity of establishing
      appropriate reference intervals for thyroid function testing for the preterm
      population.

PMID- 24125879
TI  - A possible association of low pepsinogen I and pepsinogen I/II with low and high
      body weight in Japanese men.
AB  - BACKGROUND: It is unknown whether low serum pepsinogen I and pepsinogen I/II
      ratio (PGI-PGI/II), a marker for chronic atrophic gastritis, is associated with
      low or high body weight. METHODS: We investigated the association between low PGI
      PGI/II and both ends of the spectrum of body mass index (BMI) in 819 apparently
      healthy Japanese men aged 20-75 years who received a medical check-up in 2008.
      RESULTS: In univariate analysis, serum pepsinogen I, but not pepsinogen II or
      pepsinogen I/II, was significantly reduced across the increasing BMI categories.
      Multivariate regression analysis showed that, compared with BMI 21.0-22.9
      kg/m(2), BMI of 20.9 kg/m(2) and less or 25.0 kg/m(2) and above was significantly
      associated with low PGI-PGI/II (pepsinogen I<50 ng/ml combined with PG I/II<3.0),
      even after adjustment for relevant confounders. These associations showed a J
      shaped curve against BMI. CONCLUSION: Low PGI-PGI/II may be independently
      associated with both low body weight and obesity in Japanese men.

PMID- 24125880
TI  - Synthesis and activity of novel tetrazole compounds and their pyrazole-4
      carbonitrile precursors against Leishmania spp.
AB  - A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a
      m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were
      synthesized and evaluated as antileishmanials against Leishmania braziliensis and
      Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of
      these compounds was evaluated on the RAW 264.7 cell line. The results showed that
      among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24h=15+/
      0.14 MUM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24h=26+/-0.09 MUM) were
      the most potent against L. braziliensis promastigotes, as compared the reference
      drug pentamidine, which presented IC50=13+/-0.04 MUM. In addition, 4a and 4d
      derivatives were less cytotoxic than pentamidine. However, these tetrazole
      derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each
      of the tested species and were more effective against L.braziliensis than on L.
      amazonensis.

PMID- 24125881
TI  - Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory
      activity.
AB  - The glycopolymers for glycosaminoglycan mimic were synthesized, and the
      inhibitory effects of Alzheimer's beta-secretase (BACE-1) were examined. The
      regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the
      acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The
      glycopolymers were synthesized with acrylamide using radical initiator. The
      glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1,
      and the inhibitory effects were dependent on the sulfation positions. Especially,
      glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect.
      The docking simulation suggested that glycopolymers bind to the active site of
      BACE-1. 

PMID- 24125882
TI  - Development of carbamate-tethered coumarins as phototriggers for caged
      nicotinamide.
AB  - The syntheses of 7-diethylaminocoumarin- or modified DEACM-nicotinamide and 6
      bromo-7-methoxycoumarin- or BMCM-nicotinamide have been accomplished by reaction
      of nicotinoyl isocyanate with the corresponding coumarin allylic alcohol
      derivatives. The resulting compounds contain an N-acyl O-alkyl carbamate as a new
      type of linkage for the caging of nicotinamide with a coumarin phototrigger,
      which undergoes cleavage upon photolysis. Our design of specific caged
      nicotinamides was based upon NBO and TD-FT calculations to predict absorption
      wavelengths and photocleavage potential. This work provides a potentially general
      method for the caging of amides with coumarin photolabile protecting groups. 

PMID- 24125883
TI  - Identification of a series of 1,3,4-trisubstituted pyrazoles as novel hepatitis C
      virus entry inhibitors.
AB  - In this report we describe the identification of novel pyrazole analogs as potent
      hepatitis C virus (HCV) entry inhibitor. The pyrazoles were identified by our
      phenotypic high-throughput screening using infectious HCV. A series of pyrazole
      derivatives was synthesized and evaluated for inhibitory activity against HCV in
      the infectious cell culture system. Through evaluation of selected compounds we
      observed that the pyrazoles did not interfere with HCV RNA replication but with
      viral entry as shown by experiments with HCV replicons and HCV pseudo particles,
      respectively. 

PMID- 24125884
TI  - Modulators of the Sphingosine 1-phosphate receptor 1.
AB  - The Sphingosine 1-phosphate receptor (S1P-R) signaling system has proven to be of
      biological and medical importance in autoimmune settings. S1P1-R is a validated
      drug target for multiple sclerosis (MS) for which FTY720 (Fingolimod), a S1P1,3-5
      R pan-agonist, was recently approved as the first orally active drug for the
      treatment of relapsing-remitting MS. Transient bradycardia and long half-life are
      the FTY720 critical pitfalls. This review provides the latest advances on next
      generation S1P1-R modulators from 2012 up to date, with an overview of the
      chemical structures, structure-activity relationships, and relevant biological
      and clinical properties. 

PMID- 24125885
TI  - Targeting the hydrophobic region of Hsp90's ATP binding pocket with novel 1,3,5
      triazines.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important
      role in regulating the maturation and stabilization of many oncogenic proteins.
      In an attempt to discover a new class of Hsp90 inhibitors, a series of 1,3,5
      triazine compounds were rationally designed, synthesized, and their biological
      activities were evaluated. Compound 3b was found to degrade Hsp90's client
      proteins of Her2, Met and Akt and to induce the expression level of Hsp70. The
      binding mode of 3b in the ATP-binding site of Hsp90 was predicted by the
      molecular docking. 

PMID- 24125886
TI  - Scaffold hopping approach towards various AFQ-056 analogs as potent metabotropic
      glutamate receptor 5 negative allosteric modulators.
AB  - The metabotropic glutamate receptor subtype 5 has evolved into a promising target
      for the treatment of various diseases of the central nervous system, such as
      Fragile X and L-DOPA induced dyskinesia. One of the most advanced clinical
      compound is Novartis' AFQ-056 (Mavoglurant), which served us as a template for a
      scaffold hopping approach, generating a structurally diverse set of potent
      analogs. Both the limited aqueous solubility and the relatively poor metabolic
      stability of AFQ-056 were improved with hexahydrocyclopenta[c]pyrrole derivative
      54a, which proved to be a valuable candidate for further development.

PMID- 24125887
TI  - Fluorescent conjugate of sLe(x)-selective bisboronic acid for imaging
      application.
AB  - Carbohydrate-based biomarkers such as sialyl Lewis X are known to correlate with
      cancer formation and progression. By targeting sialyl Lewis X, we have developed
      a boronolectin-fluorophore conjugate, which was able to selectively label and
      image xenograft (sc) tumor. This represents the very first example that a small
      molecule capable of recognizing a carbohydrate biomarker was used for optical
      imaging application. 

PMID- 24125888
TI  - Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors.
AB  - A class of tripeptidyl transition state inhibitors containing a P1 glutamine
      surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit
      Norwalk virus replication in enzyme and cell based assays. An array of warheads,
      including aldehyde, alpha-ketoamide, bisulfite adduct, and alpha
      hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2
      and 6 possess antiviral activities against noroviruses, human rhinovirus, severe
      acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad
      range of antiviral activities. 

PMID- 24125889
TI  - Novel cancer-targeting SPECT/NIRF dual-modality imaging probe (99m)Tc-PC-1007:
      synthesis and biological evaluation.
AB  - Synthesis, characterization, in vitro and in vivo biological evaluation of a
      heptamethine cyanine based dual-mode single-photon emission computed tomography
      (SPECT)/near infrared fluorescence (NIRF) imaging probe (99m)Tc-PC-1007 is
      described. (99m)Tc-PC-1007 exhibited preferential accumulation in human breast
      cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of (99m)Tc-PC-1007
      was performed in a breast cancer xenograft model. The probe uptake ratio of tumor
      to control (spinal cord) was calculated to be 4.02+/-0.56 at 6 h post injection
      (pi) and 8.50+/-1.41 at 20 h pi (P<0.0001). Pharmacokinetic parameters such as
      blood clearance and organ distribution were assessed.

PMID- 24125890
TI  - The role of glucocorticoids, catecholamines and endocannabinoids in the
      development of traumatic memories and posttraumatic stress symptoms in survivors
      of critical illness.
AB  - Critically ill patients are at an increased risk for traumatic memories and post
      traumatic stress disorder (PTSD). Memories of one or more traumatic events play
      an important part in the symptom pattern of PTSD. Studies in long-term survivors
      of intensive care unit (ICU) treatment demonstrated a clear and vivid recall of
      traumatic experiences and the incidence and intensity of PTSD symptoms increased
      with the number of traumatic memories present. Preclinical evidence has clearly
      shown that the consolidation and retrieval of traumatic memories is regulated by
      an interaction between the noradrenergic, the glucocorticoid and the
      endocannabinoid system. Critically ill patients in the ICU frequently require
      treatment with adrenenergic or glucocorticoid drugs and often receive sedative
      medications; among them propofol is known to influence endocannabinoid signaling.
      Critical illness could therefore represent a useful model for investigating
      adrenergic, glucocorticoid as well as endocannabinoid effects on traumatic memory
      and PTSD development in stressed humans. The endocannabinoid system is an
      important regulator of HPA-axis activity during stress, an effect which has also
      been demonstrated in humans. Likewise, a single nucleotide polymorphism (SNP) of
      the glucocorticoid receptor (GR) gene (the BclI-SNP), which enhances the
      sensitivity of the glucocorticoid receptors to cortisol and possibly HPA-axis
      feedback function, was associated with enhanced emotional memory performance in
      healthy volunteers. The presence of the BclI-SNP increased the risk for traumatic
      memories and PTSD symptoms in patients after ICU therapy and was linked to lower
      basal cortisol levels. A number of small studies have demonstrated that the
      administration of cortisol to critically ill or injured patients results in a
      significant reduction of PTSD symptoms after recovery without influencing the
      number of traumatic memories. These glucocorticoid effects can possibly be
      explained by a cortisol-induced temporary impairment in traumatic memory
      retrieval which has previously been demonstrated in both rats and humans. The
      hypothesis that stress doses of glucocorticoids or the pharmacologic manipulation
      of glucocorticoid-endocannabinoid interaction during traumatic memory
      consolidation and retrieval could be useful for prophylaxis and treatment of PTSD
      after critical illness should be tested in larger controlled studies. 

PMID- 24125891
TI  - Modulation of haloperidol-induced catalepsy in rats by GABAergic neural substrate
      in the inferior colliculus.
AB  - Not only is the inferior colliculus (IC) a highly important center of integration
      within the central auditory pathway, but it may also play a modulatory role in
      sensory-motor circuitry. Previous evidence from our laboratory relating the IC to
      motor behavior shows that glutamate-mediated mechanisms within the IC modulate
      haloperidol-induced catalepsy. The high density of GABAergic receptors in the IC
      led to this study of a possible link between these receptors, haloperidol-induced
      catalepsy, and a possible involvement of the blockade of dopaminergic receptors.
      Catalepsy was evaluated by positioning both forepaws of rats on an elevated
      horizontal wooden bar and recording the time that the animal maintained this
      position. The present study shows that haloperidol-induced catalepsy was enhanced
      by local microinjection into the IC of midazolam (20nmol/0.5MUl), a
      benzodiazepine receptor agonist, whereas animals receiving a microinjection of
      bicuculline (40 or 80ng/0.5MUl), a GABAergic antagonist, showed a reduction in
      the time of catalepsy. However, the microinjection of haloperidol (2.5 or
      5.0MUg/0.5MUl) bilaterally into the IC did not induce catalepsy. Therefore, our
      results suggest the involvement of the IC in the modulation of catalepsy induced
      by haloperidol, even though the dopaminergic mechanisms of the IC are unable to
      induce catalepsy when blocked by the direct microinjection of haloperidol. It is
      thus possible that the IC plays a role in sensorimotor gating and that GABA
      mediated mechanisms are involved. 

PMID- 24125892
TI  - White matter lactate--does it matter?
AB  - About half of the human brain is white matter, characterized by axons covered in
      myelin, which facilitates the high speed of nerve signals from one brain area to
      another. At the time of myelination, the oligodendrocytes that synthesize myelin
      require a large amount of energy for this task. Conditions that deprive the
      tissue of energy can kill the oligodendrocytes. During brain development, the
      oligodendrocytes may use lactate as an alternative source of energy and material
      for myelin formation. Mature oligodendrocytes, however, can release lactate
      through the myelin sheath as nutrient for axons. In addition, lactate carries
      signals as a volume transmitter. Myelin thus seems to serve as a provider of
      substrates and signals for axons, and not as a mere insulator. We review the
      fluxes of lactate in white matter and their significance in brain function. 

PMID- 24125893
TI  - Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin
      American patients.
AB  - In this study, 103 unrelated South-American patients with mucopolysaccharidosis
      type II (MPS II) were investigated aiming at the identification of iduronate-2
      sulfatase (IDS) disease causing mutations and the possibility of some insights on
      the genotype-phenotype correlation The strategy used for genotyping involved the
      identification of the previously reported inversion/disruption of the IDS gene by
      PCR and screening for other mutations by PCR/SSCP. The exons with altered
      mobility on SSCP were sequenced, as well as all the exons of patients with no
      SSCP alteration. By using this strategy, we were able to find the pathogenic
      mutation in all patients. Alterations such as inversion/disruption and
      partial/total deletions of the IDS gene were found in 20/103 (19%) patients.
      Small insertions/deletions/indels (<22 bp) and point mutations were identified in
      83/103 (88%) patients, including 30 novel mutations; except for a higher
      frequency of small duplications in relation to small deletions, the frequencies
      of major and minor alterations found in our sample are in accordance with those
      described in the literature.

PMID- 24125894
TI  - Partial updating of clinical practice guidelines often makes more sense than full
      updating: a systematic review on methods and the development of an updating
      procedure.
AB  - OBJECTIVES: To conduct a systematic review of the methods used to determine when
      and how to update clinical practice guidelines (CPGs) and develop a procedure for
      updating CPGs. STUDY DESIGN AND SETTING: We searched MEDLINE, Embase, and the
      Cochrane Methodology Register for methodological publications on updating CPGs.
      Guideline development manuals were obtained from the Web sites of guideline
      developing organizations. Using the information obtained from these records, a
      procedure for updating CPGs was developed. RESULTS: A total of 5,116 journal
      articles were screened, and seven articles met the criteria for inclusion. Forty
      seven manuals were included; of these, eight included details about the methods
      used to update the guidelines. Most of the included publications focused on
      assessing whether the CPGs needed updating and not on how to update them. The
      developed procedure includes a systematic monitoring system and a scheduled
      process for updating the CPGs, which includes guidance on how to determine the
      type and scope of an update. CONCLUSION: Partial updating often makes more sense
      than updating the whole CPG because topics and recommendations differ in terms of
      the need for updating. Guideline developers should implement a systematic
      updating procedure that includes an ongoing monitoring system that is appropriate
      for the nature of the guideline topics and the capabilities of the developers.

PMID- 24125895
TI  - The Quality of Life Questionnaire Core 30 (QLQ-C30) and Functional Assessment of
      Cancer-General (FACT-G) differ in responsiveness, relative efficiency, and
      therefore required sample size.
AB  - OBJECTIVES: Quality of Life Questionnaire Core 30 (QLQ-C30) and Functional
      Assessment of Cancer Therapy-General (FACT-G) are widely used cancer-specific
      health-related quality of life (HRQOL) questionnaires. We aimed to compare their
      responsiveness with clinically important effects and statistical efficiency to
      detect such effects. STUDY DESIGN AND SETTING: Secondary analysis of QLQ-C30 and
      FACT-G data from a randomized controlled trial of Medical Qigong (n = 162
      heterogeneous cancer patients). Difference in responsiveness (DR) and relative
      efficiency (RE) were calculated for five domains. RESULTS: FACT-G total score was
      more efficient than QLQ-C30 global scale for detecting change within the
      intervention arm [RE = 0.31 (0.083, 0.69)] and comparing change between trial
      arms [RE = 0.17 (0.009, 0.58)]. In the social domain, the QLQ-C30 scale was more
      responsive [DR = 0.28 (0.024, 0.54)] and more efficient within arm only [RE =
      5.25 (1.21, 232.26)]. In the physical, functional/role, and emotional domains,
      neither questionnaire was more responsive or efficient. CONCLUSION: FACT-G would
      require about one-third the sample of QLQ-C30 to detect a given change in overall
      HRQOL, whereas in the social domain, it would require five times the sample size.
      FACT-G won advantage in overall HRQOL by reduced "noise" (smaller standard
      deviation achieved by summing across 27 items), whereas QLQ-C30 won advantage in
      the social domain via a larger "signal" (achieved through well-targeted item
      content).

PMID- 24125896
TI  - Childhood cancer survivor to emerging health professional: carrying on with
      creativity.

PMID- 24125897
TI  - Comfort and performance of power line maintainers' gloves during electrical
      utility work in the cold.
AB  - BACKGROUND: Electrical utility workers wear thick rubber gloves and often work in
      the cold. OBJECTIVE: To document the challenge of working in the cold and the
      effectiveness of different glove/liner combinations in keeping workers' hands
      warm. METHODS: Ten experienced male electrical utility employees worked in a
      controlled temperature walk-in chamber at -20  degrees C for 45 minutes for each
      of five glove conditions: standard five-finger rubber gloves with cotton liners
      and gauntlets, mitten style gloves, a prototype wool liner, and two heating
      options; glove or torso. Dependent measures were maximum grip force, skin
      temperatures, finger dexterity and sensitivity to touch, ratings of perceived
      effort and a rating of thermal sensation. RESULTS: Participants' hand skin
      temperatures decreased, they perceived their hands to be much colder, their
      finger sensitivity decreased and their ratings of perceived exertion increased,
      however their performance did not degrade over the 45 minute trials. The mitten
      style gloves showed a smaller drop in skin temperature for the 3rd and 5th digits
      (p< 0.05) than the other glove conditions. CONCLUSIONS: Mitten style gloves kept
      workers' hands warmer than the standard five finger glove.

PMID- 24125898
TI  - Canadian researchers at WORK: celebrating the career of Dr. Joan Stevenson.

PMID- 24125899
TI  - A journey to make cancer rehabilitation the standard of care.

PMID- 24125900
TI  - Selecting seats for steel industry mobile machines based on seat effective
      amplitude transmissibility and comfort.
AB  - OBJECTIVE: The purpose of this work was to help a steel industry partner select
      the most appropriate of three high end heavy equipment seats to retrofit a number
      of their heavy mobile machines used in the steel making process. PARTICIPANTS:
      The participants included 8 males (22.3 +/- 2.0 yrs.) and 8 females (23.5 +/- 1.8
      yrs.) with no experience operating heavy mobile equipment. METHODS: Previously
      recorded 6-DOF chassis acceleration data from a Pot Hauler (a machine which picks
      up and transports pots of slag) were used to extract six, 20 second
      representative profiles for implementation on a lab-based heavy machine simulator
      (6-DOF Parallel Robotics System Corporation robot). Subjects sat on three heavy
      equipment seats (BeGe7150, Grammar MSG 95G1721, and a 6801 Isringhausen with the
      seat pan cushion retrofitted with a Skydex cushion) mounted on the simulator.
      Each subject completed three trials for each combination of seat (n=3) and
      vibration profile (n=6). Chassis and operator/seat interface vibration were
      measured by 2, 6-DOF vibration transducers. Variables included Seat Effective
      Amplitude Transmissibility (SEAT) (X,Y,Z,Roll,Pitch,Yaw,6DOF Vector Sum) to
      determine if the seat was attenuating or amplifying the vibration, 6-degree of
      freedom (DOF) vibration total value weighted predicted comfort (Avc) (according
      to ISO 2631-1) and operator reported comfort (ORC). RESULTS: Factorial ANOVAs
      revealed significant differences (p < or = 0.05) between seats for all SEAT
      variables but different seats performed better than others depending on the axis.
      Significant differences between males and females were observed for SEAT in X,Y,
      and Pitch as well as for Avs. As expected there were significant differences
      between vibration profiles for all assessed variables. A number of interaction
      effects were observed, the most frequently occurring of which was between seat
      and vibration profile. CONCLUSIONS: Based upon the number of seat and vibration
      profile interactions, results suggest that a single seat is not suited for all
      tested conditions. However, SEAT values for all of the seats tested were
      extremely low (e.g., 6-DOF SEAT < 30%) indicating that all of the seats were
      capable of providing good vibration attenuation.

PMID- 24125901
TI  - Cancer rehabilitation may improve function in survivors and decrease the economic
      burden of cancer to individuals and society.
AB  - BACKGROUND: Cancer and its treatment may cause physical impairments and
      psychological distress in survivors. Rehabilitation is a critical component of
      quality cancer care, returning survivors to their highest functional potential.
      OBJECTIVE: This overview focuses on the benefits of multidisciplinary cancer
      rehabilitation - including improving physical function, reducing psychological
      distress, promoting return to work and, therefore, decreasing the economic burden
      of cancer and its treatment on individuals and society in general. METHODS:
      Relevant literature was identified through a search of the PubMed database and
      reviewed for its relevance to cancer rehabilitation and the topic of this
      article. Search terms included, but were not limited to, cancer rehabilitation,
      cancer prehabilitation, disability, return to work, employment, and unemployment.
      RESULTS: Cancer survivors are less likely to be employed and take more sick leave
      than workers without a history of cancer. Pain, musculoskeletal issues,
      deconditioning, fatigue, balance, psychosocial issues, and lymphedema are most
      amenable to rehabilitation. CONCLUSION: Overall health and the need for work
      accommodations must be addressed in order to improve return to work and
      subsequent productivity in cancer survivors. Survivors are usually best served by
      a multidisciplinary care team comprising members who can address the myriad
      impairments affecting survivor function.

PMID- 24125902
TI  - Effects of tetrachloroethene on the measurement of radon in water with liquid
      scintillation counting method.
AB  - This study investigated the effects of tetrachloroethene (PCE) on radon
      measurements that employed the liquid scintillation counting (LSC) method
      referring to 7500-Rn B of Standard Methods for the Examination of Water and
      Wastewater. Laboratory-produced radon-enriched water was used to compare the
      counting rates of the radon water with and without PCE addition, and groundwater
      samples from a site contaminated by chlorinated solvents were used to investigate
      the application of the laboratory experiments. The results showed that the major
      factor reducing counting efficiency was resulted from the interaction between PCE
      and a cocktail through the quench effect. The counting rate showed an
      exponentially decreasing trend when PCE addition was increased. The results
      indicated that a small addition of PCE reduced the counting rate considerably. An
      alternative energy channel 500-1000 to the optimal channel was suggested to
      attenuate the quench effect on radon measurement. The quench effect was also
      observed on samples from a site contaminated by chlorinated solvents. The
      concepts and procedures presented in this study are a reference for future
      research on the topic of chlorinated solvents or other quench chemicals involving
      in radon measurement. 

PMID- 24125903
TI  - A time dependent behavior of radiocesium from the Fukushima-fallout in
      litterfalls of Japanese flowering cherry trees.
AB  - Radiocesium ((134)Cs + (137)Cs) concentrations, primarily derived from the
      Fukushima accident in March 2011, were measured in litterfalls and green leaves
      of Japanese flowering cherry trees (Prunus x yedoensis cv. Somei-Yoshino). The
      sampling was performed mainly during the defoliation season in 2011 and 2012
      using traps to collect litterfalls before contact with the ground. The average
      radiocesium concentration in litterfalls in 2012 fell to one-third of that in
      2011 (0.43 and 1.2 kBq kg-DW(-1), respectively). Interestingly, the
      concentrations in litterfalls collected in late autumn in both 2011 and 2012
      (0.68 and 0.19 kBq kg-DW(-1), respectively) were significantly lower than those
      in litterfalls collected in the early autumn (1.7 and 1.1 kBq kg-DW(-1),
      respectively). In addition, the reductions in radiocesium concentrations in the
      litterfall were nearly synchronous with those in potassium concentrations (p <=
      0.05). On the contrary, radiocesium concentrations in green leaves were also
      correlated with potassium concentrations; however, the slopes of the regression
      lines between the radiocesium and potassium concentrations were very similar in
      the 2011 litterfalls and the 2012 litterfalls, while the slopes were
      significantly different between these litterfalls and the green leaves.
      Consequently, the correlation between potassium and radiocesium was clear but
      independently observable in each of the litterfalls and the green leaves. It is
      possible that the reduction in radiocesium concentration occurred as a part of
      physiological demand, a translocation of potassium from the leaves to the
      body/twigs. 

PMID- 24125904
TI  - Molecular epidemiology of Staphylococcus aureus bacteremia in children, Spain:
      low risk of methicillin resistance.

PMID- 24125905
TI  - Mechanically tissue-like elastomeric polymers and their potential as a vehicle to
      deliver functional cardiomyocytes.
AB  - One of the major challenges in the field of biomaterials engineering is the
      replication of the non-linear elasticity observed in soft tissues. In the present
      study, non-linearly elastic biomaterials were successfully fabricated from a
      chemically cross-linked elastomeric poly(glycerol sebacate) (PGS) and
      thermoplastic poly(L-lactic acid) (PLLA) using the core/shell electrospinning
      technique. The spun fibrous materials, containing a PGS core and PLLA shell,
      demonstrated J-shaped stress-strain curves, and having ultimate tensile strength,
      rupture elongation, and stiffness constants respectively comparable to muscle
      tissue properties. In vitro evaluations also showed that PGS/PLLA fibrous
      biomaterials possess excellent biocompatibility, capable of supporting human stem
      cell-derived cardiomyocytes over several weeks in culture. Therefore, the
      core/shell electrospun elastomeric materials provide a new potential scaffold to
      support cells in the therapy of a wide range of soft tissues exposed to cyclic
      deformation, such as tendon, ligament, cardiac or smooth muscle and lung
      epithelium. 

PMID- 24125907
TI  - Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion
      membranes of pregnancies complicated by histologic chorioamnionitis.
AB  - OBJECTIVES: To determine whether histologic chorioamnionitis is associated with
      changes in gene expression of TLR-1, -2, -4 and -6, and to describe the
      localization of these receptors in fetal membranes. STUDY DESIGN: A total of 135
      amniochorion membranes with or without histologic chorioamnionitis from preterm
      or term deliveries were included. Fragments of membranes were submitted to total
      RNA extraction. RNA was reverse transcribed and the quantification of TLRs
      expression measured by real time PCR. RESULTS: All amniochorion membranes
      expressed TLR-1 and TLR-4, whereas 99.1% of membranes expressed TLR-2 and 77.4%
      expressed TLR-6. TLR-1 and TLR-2 expressions were significantly higher in
      membranes with histologic chorioamnionitis as compared to membranes without
      chorioamnionitis in preterm pregnancies (p=0.003 and p<0.001, respectively).
      Among the membranes of term pregnancies there were no differences in the
      expressions of such receptors regardless of inflammatory status. Regarding TLR-4
      and TLR-6 expression, there was no difference among membranes with or without
      histologic chorioamnionitis, regardless gestational age at delivery. TLR-1, TLR
      2, TLR-4 and TLR-6 expressions were observed in amniotic epithelial, chorionic
      and decidual cells. CONCLUSION: Amniochorion membranes express TLR-1, TLR-2, TLR
      4 and TLR-6 and increased expression of TLR-1 and TLR-2 is related to the
      presence of histologic chorioamnionitis in preterm pregnancies. This study
      provides further evidence that amniochorion membranes act as a mechanical barrier
      to microorganisms and as components of the innate immune system.

PMID- 24125906
TI  - Microenvironmental regulation of cancer metastasis by miRNAs.
AB  - miRNAs are a class of small, non-coding RNAs that regulate cancer progression,
      especially the processes of invasion and metastasis. Although earlier studies in
      metastasis primarily focused on the impact that miRNAs have on the intrinsic
      properties of cancer cells, recent reports reveal that miRNAs also shape
      interactions between cancer cells and their associated stroma. In this review, we
      discuss current known mechanisms by which miRNAs execute their microenvironmental
      regulation of cancer metastasis, including regulating expression of cell membrane
      bound and secreted proteins or directly transmitting mature miRNAs between
      different cell types. The significance of miRNA-mediated tumor-stroma
      interactions in regulating metastasis suggests that miRNAs may be a potential
      therapeutic target. 

PMID- 24125908
TI  - Ca analysis: an Excel based program for the analysis of intracellular calcium
      transients including multiple, simultaneous regression analysis.
AB  - Here I present an Excel based program for the analysis of intracellular Ca
      transients recorded using fluorescent indicators. The program can perform all the
      necessary steps which convert recorded raw voltage changes into meaningful
      physiological information. The program performs two fundamental processes. (1) It
      can prepare the raw signal by several methods. (2) It can then be used to analyze
      the prepared data to provide information such as absolute intracellular Ca
      levels. Also, the rates of change of Ca can be measured using multiple,
      simultaneous regression analysis. I demonstrate that this program performs
      equally well as commercially available software, but has numerous advantages,
      namely creating a simplified, self-contained analysis workflow. 

PMID- 24125909
TI  - Epidemiology of cycling for exercise, recreation or sport in Australia and its
      contribution to health-enhancing physical activity.
AB  - OBJECTIVES: To provide population estimates and explore trends for recreational
      cycling by subgroups, and to understand the contribution of recreational cycling
      to meeting the physical activity guidelines among Australian adults. DESIGN:
      Repeated cross sectional population surveys. METHODS: Data from the Exercise,
      Recreational and Sport Survey (ERASS) for the years 2001-2009 were used.
      Approximately 13,000 Australian adults (>= 15 years) were interviewed each year
      across all seasons. Data include frequency of cycling during the previous 12
      months and average duration of a cycling session, asked since 2005. Three
      thresholds for meeting the physical activity guidelines were considered using the
      separate categories: achieving >150 min, >300 min, and 5 sessions of 30 min
      cycling per week. RESULTS: The pooled prevalence of recreational cycling was 10%.
      Employed middle-aged men with tertiary education reported the highest prevalence
      of recreational cycling. An increase in cycling was observed over time, mainly
      attributed to an increase in "irregular" cycling (<1/week). Among all cyclists a
      third met the physical activity guidelines of 150 min/week, and less than 20% met
      the guidelines of 300 min/week or 5 sessions of 30 min/week, respectively.
      Although a small group, almost two thirds of those participating in organised or
      partly organised recreational cycling met the guidelines. CONCLUSIONS:
      Recreational cycling is a plausible way to accumulate sufficient health-enhancing
      physical activity. The majority of recreational cyclists do not cycle in
      organised rides. Targeted efforts are needed to exploit the full potential of
      recreational cycling for public health.

PMID- 24125910
TI  - Effect of DNA extraction and sample preservation method on rumen bacterial
      population.
AB  - The comparison of the bacterial profile of intracellular (iDNA) and extracellular
      DNA (eDNA) isolated from cow rumen content stored under different conditions was
      conducted. The influence of rumen fluid treatment (cheesecloth squeezed,
      centrifuged, filtered), storage temperature (RT, -80  degrees C) and
      cryoprotectants (PBS-glycerol, ethanol) on quality and quantity parameters of
      extracted DNA was evaluated by bacterial DGGE analysis, real-time PCR
      quantification and metabarcoding approach using high-throughput sequencing.
      Samples clustered according to the type of extracted DNA due to considerable
      differences between iDNA and eDNA bacterial profiles, while storage temperature
      and cryoprotectants additives had little effect on sample clustering. The numbers
      of Firmicutes and Bacteroidetes were lower (P < 0.01) in eDNA samples. The qPCR
      indicated significantly higher amount of Firmicutes in iDNA sample frozen with
      glycerol (P < 0.01). Deep sequencing analysis of iDNA samples revealed the
      prevalence of Bacteroidetes and similarity of samples frozen with and without
      cryoprotectants, which differed from sample stored with ethanol at room
      temperature. Centrifugation and consequent filtration of rumen fluid subjected to
      the eDNA isolation procedure considerably changed the ratio of molecular
      operational taxonomic units (MOTUs) of Bacteroidetes and Firmicutes.
      Intracellular DNA extraction using bead-beating method from cheesecloth sieved
      rumen content mixed with PBS-glycerol and stored at -80  degrees C was found as
      the optimal method to study ruminal bacterial profile. 

PMID- 24125911
TI  - A faster reconstitution of hematopoiesis after autologous transplantation of
      hematopoietic cells cryopreserved in 7.5% dimethyl sulfoxide if compared to 10%
      dimethyl sulfoxide containing medium.
AB  - Our previous in vitro studies proved a higher clonogenic potential of peripheral
      blood progenitor cells cryopreserved in 7.5% dimethyl sulfoxide (Me2SO) than in
      10% Me2SO containing medium. Based on this findings 7.5% Me2SO cryopreservation
      medium was introduced to our protocol and both the hematopoietic recovery and
      infusion-related toxicity were compared with that obtained with standard 10%
      Me2SO containing solution. Two cohorts of consecutive patients treated with
      autologous hematopoietic stem cell transplantation were included in the analysis:
      56 patients with PBPCs cryopreserved in 7.5% Me2SO solution and 52 patients who
      obtained cells cryopreserved in 10% Me2SO. Both study groups did not differ
      significantly with regard to age, diagnosis, and the number of transplanted
      CD34(+) cells. The time to leukocyte recovery was shorter for patients in the
      7.5% Me2SO treated group than in the 10% one. Reconstitution of platelets and the
      frequency of adverse events did not differ in both groups. Reduction of Me2SO
      concentration from 10% to 7.5% in cryoprotective mixture has a beneficial impact
      on leukocyte recovery. These findings require verification in a prospective,
      randomized trial. 

PMID- 24125913
TI  - In Memory and In Honor of Signe Skott Cooper 1921-2013.

PMID- 24125912
TI  - A model for predicting the permeation of dimethyl sulfoxide into articular
      cartilage, and its application to the liquidus-tracking method.
AB  - Long-term storage of articular cartilage (AC) has excited great interest due to
      the practical surgical significance of this tissue. The liquidus-tracking (LT)
      method developed by Pegg et al. (2006) [29] for vitreous preservation of AC
      achieved reasonable survival of post-warming chondrocytes in situ, but the design
      of the entire procedure was more dependent on trial and error. Mathematical
      modeling would help to better understand the LT process, and thereby make
      possible improvements to attain higher cell survival. Mass transfer plays a
      dominant role in the LT process. In the present study, a diffusion model based on
      the free-volume theory and the Flory-Huggins thermodynamics theory was developed
      to predict the permeation of dimethyl sulfoxide (Me2SO) into AC. A comparison
      between the predicted mean concentration of Me2SO in the AC disc and the
      experimental data over wide temperature and concentration ranges [-30 to 37 
      degrees C, 10 to 64.5% (w/w)] shows that the developed model can accurately
      describe the permeation of Me2SO into AC [coefficient of determination (R(2)):
      0.951-1.000, mean relative error (MRE): 0.8-12.8%]. With this model, the spatial
      and temporal distribution of Me2SO in the AC disc during a loading/unloading
      process can be obtained. Application of the model to Pegg et al.'s LT procedure
      revealed that the liquidus line is virtually not followed for the center part of
      the AC disc. The presently developed model will be a useful tool in the analysis
      and design of the LT method for vitreous preservation of AC.

PMID- 24125914
TI  - Continuing Education and Self-Assessment of Knowledge of Nurse Leaders.

PMID- 24125915
TI  - Biotransformation on the flavonolignan constituents of Silybi Fructus by an
      intestinal bacterial strain Eubacterium limosum ZL-II.
AB  - Eubacterium limosum ZL-II is an anaerobic bacterium with demethylated activity,
      which was isolated from human intestinal bacteria in our previous work. In this
      study, the flavonolignan constituents of Silybi Fructus were biotransformed by E.
      limosum(1) ZL-II, producing four new transformation products - demethylisosilybin
      B (T1), demethylisosilybin A (T2), demethylsilybin B (T3) and demethylsilybin A
      (T4), among which T1 and T2 were new compounds. Their chemical structures were
      identified by ESI-TOF/MS, (1)H NMR, (13)C NMR, HMBC and CD spectroscopic data.
      The bioassay results showed that the transformation products T1-T4 exhibited
      significant inhibitory activities on Alzheimer's amyloid-beta 42 (Abeta42(2))
      aggregation with IC50 values at 7.49 MUM-10.46 MUM, which were comparable with
      that of the positive control (epigallocatechin gallate, EGCG(3), at 9.01 MUM) and
      much lower than those of their parent compounds (at not less than 145.10 MUM).
      The method of biotransformation by E. limosum ZL-II explored a way to develop the
      new and active lead compounds in Alzheimer's disease from Silybi Fructus.
      However, the transformation products T1-T4 exhibited decreased inhibitory
      activities against human tumor cell lines comparing with their parent compounds.

PMID- 24125916
TI  - St. John's Wort seed and feverfew flower extracts relieve painful diabetic
      neuropathy in a rat model of diabetes.
AB  - Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes
      and the few approved therapies for the management of pain have limited efficacy
      and side effects. With the aim to explore and develop new pharmacological
      treatments, we investigated the antihyperalgesic properties of St. John's Wort
      (SJW) and feverfew in streptozotocin (STZ)-diabetic rats. Acute administration of
      a SJW seed extract reversed mechanical hyperalgesia with a prolonged effect. A
      SJW extract obtained from the aerial portion of the plant and a feverfew flower
      extract partially relieved neuropathic pain whereas a feverfew leaf extract was
      ineffective. The antihyperalgesic efficacy of these herbal drugs was comparable
      to that of clinically used antihyperalgesic drugs (carbamazepine, lamotrigine, l
      acetyl-levocarnitine). Further examinations of SJW and feverfew composition
      revealed that hyperforin and hypericin might be responsible for the
      antihyperalgesic properties of SJW whereas the efficacy of feverfew seems to be
      related to the presence of parthenolide. Rats undergoing treatment with SJW and
      feverfew did not show any behavioral side effect or sign of altered locomotor
      activity. Our results suggest that SJW and feverfew extracts may become new
      therapeutic perspectives for painful DPN. 

PMID- 24125917
TI  - [Obstacles perceived by nurses for evidence-based practice: a qualitative study].
AB  - AIMS: To examine the obstacles perceived by nurses to implement an evidence-based
      clinical practice. METHOD: A qualitative study through semi-structured interviews
      conducted in 2010-2011 including 11 nurses purposively selected from public
      hospitals and community centres in Jaen and Cordoba (Spain). A content analysis
      was performed, using Miles and Huberman as a reference and comprising the
      following steps: data reduction, data presentation, and data
      conclusion/verification. Data saturation was reached in these categories
      (obstacles). RESULTS: The obstacles perceived by nurses to introduce an evidence
      based clinical practice (EBCP) were grouped into 3 major categories: obstacles
      related with professionals (routine-based practice, unwilling and stagnant
      attitudes, and lack of training in EBCP), obstacles related to the social context
      (reluctance from other professionals and from patients or families), and
      obstacles related to the organization (obsolete cultures that do not promote
      innovation in nursing care). CONCLUSIONS: This study highlights the persistence
      of various factors that hinder the use of research findings in clinical practice.
      The results underline the need to change the culture of healthcare organizations,
      to motivate professionals, and to break some of the resistance attitudes that
      hinder the implementation of evidence-based practice.

PMID- 24125918
TI  - MDCT findings of a Meckel's diverticulum with ectopic pancreatic tissue.
AB  - A Meckel's diverticulum becomes symptomatic due to complications such as
      hemorrhage or bowel obstruction. The presence of ectopic pancreatic tissue in the
      diverticulum can be associated with such complications. To our knowledge, multi
      detector row CT findings of ectopic pancreatic tissue in a Meckel's diverticulum
      have never been reported. Here, we report the multi-detector row CT features of
      the ectopic pancreatic tissue in a Meckel's diverticulum. 

PMID- 24125919
TI  - Re: "The 'case-chaos study' L adjunct or alternative to conventional case-control
      study methodology".

PMID- 24125920
TI  - Air pollution and preterm premature rupture of membranes: a spatiotemporal
      analysis.
AB  - Preterm premature rupture of membranes (PROM) is the leading identifiable
      predisposing factor for preterm birth. Although maternal exposure to air
      pollution can potentially have an impact on preterm PROM, there is no available
      evidence on such an impact. In this study, based on 5,555 singleton births
      occurring in Barcelona, Spain (2002-2005), we investigated the associations of
      maternal exposure to nitrogen dioxide, nitrogen oxides, and particulate matter
      with aerodynamic diameters of <=2.5 um (PM2.5), 2.5 um-10 um, and <=10 um and
      PM2.5 light absorption with preterm PROM and gestational age at the rupture of
      membranes (ROM). We utilized temporally adjusted land-use regression models to
      predict pollutant levels at each subject's home address during each week of her
      pregnancy. We conducted matched (according to the length of exposure) case
      control analyses to estimate the preterm PROM risk associated with 1
      interquartile-range increase in exposure levels during the entire pregnancy and
      during the last 3 months prior to ROM. We found an increase in preterm PROM risk
      of up to 50% (95% confidence interval: 4, 116) and a 1.3-day (95% confidence
      interval: -1.9, -0.6) reduction in gestational age at ROM associated with PM2.5
      absorbance, nitrogen dioxide exposure, and nitrogen oxide exposure during the
      entire pregnancy and the last 3 months prior to ROM.

PMID- 24125921
TI  - High genetic diversity of Staphylococcus aureus in a tertiary care hospital in
      Southwest Nigeria.
AB  - Phenotypic and genetic characterization of 62 Staphylococcus aureus isolates
      recovered in Nigeria indicated a high proportion of Panton-Valentine leukocidin
      positive isolates and a high genetic diversity among the 22 methicillin-resistant
      S. aureus. This underlines the need for infection control in Africa to prevent
      further dissemination of potentially highly virulent and resistant clones. 

PMID- 24125922
TI  - Carbapenemase-producing Enterobacteriaceae during 2011-12 in the Bolzano area
      (Northern Italy): increasing diversity in a low-endemicity setting.
AB  - The recent (2011-2012) distribution of carbapenemase determinants in
      Enterobacteriaceae was studied in the Bolzano area (Northern Italy). Low
      proportions of carbapenemase producers were found for Escherichia coli (0.2%),
      Citrobacter freundii (1.1%), Klebsiella pneumoniae (1.3%), Klebsiella oxytoca
      (1.6%) and Enterobacter spp (1.8%). Although VIM-1 remained the most common
      carbapenemase, the emergence of K. pneumoniae producing KPC-3 and of E. coli
      producing OXA-48 was observed. Of concern is the spread of the hyperepidemic
      strains E. coli ST131 producing VIM-1 and K. pneumoniae ST258 producing KPC-3.
      Low essential and category agreements between the reference broth microdilution
      and commercial methods were observed for carbapenems. 

PMID- 24125923
TI  - Effectiveness of latex agglutination slide test in the diagnosis of imported
      invasive amoebiasis in the emergency department.
AB  - We compared a latex agglutination test (LAT) with enzyme-linked immunosorbent
      assay and indirect hemagglutination assay in the diagnosis of invasive
      amoebiasis. A retrospective biological records review has included 639 patients
      for whom these three serological tests were performed. The sensitivity of the LAT
      was 97.8% and the specificity was 97%. 

PMID- 24125924
TI  - Strengthening partnership towards excellence in public health.

PMID- 24125925
TI  - Evolution of iodine deficiency disorders control program in India: a journey of
      5,000 years.
AB  - Iodine deficiency disorders (IDD) has been documented since around 5,000 years.
      However, geological factors like frequent glaciations, flooding, and changing of
      course of rivers has led to iodine deficiency in soil. As a result everyone
      remains at risk of IDD, if optimum intake of iodine is not sustained. Evolution
      of the IDD control program in India has been a dynamic process. The model of IDD
      control program in India provides important lessons for successful implementation
      of a national health program. In formulating National Health Programs; policy
      environment, scientific inputs, political will, and institutional structure for
      decision making are necessary but not sufficient. Continuous and dynamic
      generation of reliable and representative state and national level data,
      proactive recognition of values of key stakeholders and addressing them through
      sustained advocacy, development of partnerships among stakeholders, institutional
      continuity, and mentorship are critical for achieving sustainability of results. 

PMID- 24125926
TI  - Role of public health systems in the present health scenario: key challenges.
AB  - The health scenario in our country is rapidly changing, both in terms of the
      public health challenges that we face as well as our response to these
      challenges. As India becomes more and more developed and we have greater means at
      our disposal, our response to our health challenges must reflect our changing
      health and socio-economic status. India faces enormous challenges in the area of
      women's and children's health. India is one of the few countries that have
      recorded substantial decline in maternal mortality. India is still far from
      achieving the target set in the millennium development goals. Despite several
      growth-orientated policies adopted by the government, the widening economic,
      regional, and gender disparities are posing challenges for the health sector.
      About 75% of health infrastructure, medical manpower, and other health resources
      are concentrated in urban areas where 27% of the populations live. To reduce this
      double burden of diseases, public health has to focus on health promotion, and
      disease prevention and control, while taking into consideration the social
      determinant of health. The focus of public health is to bring about change at the
      policy level not only for preventing disease but also for the health promotion
      through organized action at societal level. 

PMID- 24125927
TI  - Quality management in healthcare.
AB  - Clinical governance and better human resource management practices are important
      planks in the current health policies emphasizing quality of patient care. There
      are numerous reasons why it is important to improve quality of healthcare,
      including enhancing the accountability of health practitioners and managers,
      resource efficiency, identifying, and minimizing medical errors while maximizing
      the use of effective care and improving outcomes, and aligning care to what
      users/patients want in addition to what they need. "Quality in health is doing
      the right things for the right people at the right time, and doing them right
      first time and every time." Quality can also refer to the technical quality of
      care, to nontechnical aspects of service delivery such as clients' waiting time
      and staff's attitudes, and to programmatic elements such as policies,
      infrastructure, access, and management. In this oration/article quality
      initiatives like Reproductive and Child Health (RCH) and National Rural Health
      Mission (NRHM) of Government of India (GOI), which concentrate on improving the
      quality of infrastructure of vast rural health facilities including sub-center,
      primary health center, and community health center has been taken into account
      with focus on improving quality of health services also. United Nation Population
      Fund (UNFPA) in collaboration with the GOI has proposed introducing quality
      assurance program for accessing and improving the quality of services at public
      sector health facilities. It is felt that improving the quality of health
      services in public sector will attract the client belonging to low economic
      strata, and surely will help in achieving the goal of the NRHM, that is,
      "Reaching the enriched with quality of health services." 

PMID- 24125928
TI  - Innovations in teaching/learning methods for medical students: research with
      mentoring.
AB  - In this era of evidence-based medicine, innovative teaching learning methods
      coupled with appropriate mentoring are required to make the undergraduate medical
      students interested in the speciality of Community Medicine. Teaching research
      methodology to medical students by a hands-on approach along with mentoring by
      involving them in small, feasible, sustainable, and replicable studies on a topic
      of interest clearly showed renewed interest among students toward the subject. 

PMID- 24125929
TI  - Status of birth preparedness and complication readiness in Uttar Dinajpur
      District, West Bengal.
AB  - CONTEXT: Birth Preparedness and Complication Readiness (BPCR) is crucial in
      averting maternal morbidity and mortality. OBJECTIVES: To find out awareness and
      practices regarding BPCR among pregnant and recently delivered women in Uttar
      Dinajpur, West Bengal. MATERIALS AND METHODS: This is a cross-sectional,
      community-based, mixed methods study. Two-stage, 40 cluster sampling technique
      was used to select three pregnant and six recently delivered women separately.
      Information on socio-demographic variables as well as awareness and practices
      regarding BPCR were collected through semi-structured interview. In-depth
      interviews with one respondent per cluster were also conducted. For statistical
      analysis Z test was used. RESULTS: Around 50% of the respondents planned for
      first antenatal check-up (ANC) within 12 weeks, four or more ANCs and
      institutional delivery. Proportion of women aware of at least one key danger sign
      each of pregnancy, labor, postpartum, and newborn ranged from 12.1% to 37.2%,
      whereas 58.3% knew at least one key component of essential newborn care. Around
      two-thirds and one-third of women, respectively, especially those from backward
      and below poverty line (BPL) families knew about cash incentive and referral
      transport schemes. Proportions of women with first ANC within 12 weeks, four or
      more ANCs, institutional delivery, saving money, identifying transport, and blood
      donor were 50.4%, 33.6%, 46.2%, 40.8%, 27.3%, and 9.6%, respectively. Hindu
      religion, backward castes, BPL status, and education >= 5 years influenced the
      practices except for two regarding ANC. Overall BPCR index of the study
      population was 34.5. CONCLUSION: Preparedness in health system, ensuring
      competence, and motivation of workers are needed for promoting BPCR among the
      study population.

PMID- 24125930
TI  - Transforming public health education in India through networking and
      collaborations: opportunities and challenges.
AB  - A competent and motivated health workforce is indispensable to achieve the best
      health outcomes possible through given available resources and circumstances.
      However, apart from the shortages and unequal distribution, the workforce has
      fallen short of responding to the public health challenges of 21 st century also
      because of primarily the traditional training of health professionals. Although,
      health professionals have made enormous contributions to health and development
      over the past century, the 20 th century educational strategies are unfit to
      tackle 21 st century challenges. One of the key recommendations of the Lancet
      Commission on Education of Health Professionals is to improve health through
      reforms of professional education by establishing networks and partnerships which
      takes advantage of information and communication linkages. The primary goal of
      this manuscript is to highlight the potential of networks and partnerships in
      advancing the agenda of educational reforms to revitalize public health education
      in India. It outlines the current status and expanding scope of public health
      education in India, existing networks of public health professionals and public
      health education institutions in the country, and opportunities, advantages and
      challenges for such networks. Although, we have networks of individuals and
      institutions in the country, there potential to bring about change has still not
      being utilized fully and effectively. Immediate collaborative efforts could be
      directed towards designing and adaptation of competency driven curriculum
      frameworks suitable of addressing public health challenges of 21 st century,
      shifting the current focus of curriculum to multidisciplinary public health
      outlook, developing accreditation mechanisms for both the programs and
      institutions, engaging in creating job opportunities and designing career
      pathways for public health professionals in public and private sector. These
      efforts could certainly be facilitated through existing networks. 

PMID- 24125931
TI  - Descriptive epidemiology of novel influenza A (H1N1), Andhra Pradesh 2009-2010.
AB  - BACKGROUND: The first case of pandemic Influenza A (H1N1) in India was reported
      from Hyderabad, Andhra Pradesh on 16 th May 2009. Subsequently, all suspected
      cases seeking treatment from A (H1N1) treatment centers and their contacts were
      tested. Laboratory confirmed cases were hospitalized and treated with antivirals
      according to national guidelines. We reviewed the surveillance data to assess the
      morbidity and mortality due to A (H1N1) in the state of Andhra Pradesh
      (population-76,210,007) during the period from May 2009 to December 2010.
      MATERIALS AND METHODS: We obtained the line-list of suspected (influenza like
      illness as per World Health Organization case definition) and laboratory
      confirmed cases of A (H1N1) from the state unit of integrated disease
      surveillance project. We analyzed the data to describe the distribution of case
      patients by time, place and person. RESULTS: During May 2009 to December 2010, a
      total of 6527 suspected (attack rate: 8.6/100,000) and 1480 (attack rate:
      1.9/100,000) laboratory confirmed cases were reported from the State. Nearly 90%
      of the suspected and 93% of the confirmed cases was from nine districts of
      Telangana region, which includes Hyderabad. Nearly 65% of total confirmed cases
      were reported from Hyderabad. The attack rate was maximum (2.6/100,000) in the
      age group of 25-49 years. The cases peaked during August-October. 109 case
      patients died (Case fatality ratio: 7%) and most (80%) of these patients had
      comorbid conditions such as diabetes (24%), chronic obstructive pulmonary disease
      (20%), hypertension (11%) and pregnancy (11%). Case fatality was higher (16%)
      among patients who were older than 60 years of age compared with other age
      groups. CONCLUSIONS: In Andhra Pradesh, H1N1 transmission peaked during August
      October months and predominately affected adults. Case fatality was higher in
      patients older than 60 years with comorbid conditions.

PMID- 24125932
TI  - Integration of healthcare programs: a long-term policy perspective for a
      sustainable HIV program for India.
AB  - With the Government of India's initiative to ensure Universal Access to health
      through its flagship program of National Rural Health Mission, the debate on the
      economic efficiency and sustainability of a 'stand-alone' over 'integrated'
      programs has become extremely relevant. This study was conducted with the aim to
      establish opinion on the issue of sustainability of 'stand-alone' HIV program in
      India. Experts working on health policy development and implementation at various
      were interviewed on this issue and majority of experts interviewed were of the
      opinion that a 'stand-alone' HIV program is not sustainable in the long run
      because of inefficient use of resources. Integration of HIV program with the
      general health system is essential but it needs extensive planning. Areas like
      HIV testing centers, prevention of parent to child transmission and sexually
      transmitted infection diagnosis and treatment can be integrated with the general
      health system immediately. 

PMID- 24125933
TI  - Association of child feeding practices with nutritional status of under-two slum
      dwelling children: a community-based study from West Bengal, India.
AB  - A cross-sectional study was conducted among 245 under-two slum-dwelling children
      in Bankura town, West Bengal, to assess their feeding practices and its
      association with nutritional status. Child's gender, number of family members,
      standard of living (SLI), and household food security (HFS) were assessed through
      interview of mothers/ caregivers. Child feeding practices were measured with
      Composite Child Feeding Index comprising of age-appropriate, multiple, infant and
      young child feeding (IYCF) indicators and expressed in standardized IYCF score.
      Weight and length of the children were measured and the nutritional status was
      assessed using World Health Organization Growth Standard 2006. Standardized IYCF
      score was significantly lower in undernourished children than those with normal
      grades. Per unit increase in standardized IYCF score was likely to reduce the
      prevalence of underweight, stunting and wasting by 2-3% after adjusting for other
      variables. Low/ very low HFS, low SLI and female gender were associated with
      underweight and stunting. 

PMID- 24125934
TI  - Reasons for default from treatment of chronic illnesses in a primary healthcare
      program in rural Tamil Nadu.
AB  - Chronic illnesses are an increasing cause of morbidity and mortality in rural
      India. Many patients default from treatment, and exploring their reasons for the
      same may suggest strategies to improve service accessibility and acceptability. A
      qualitative study was conducted of 22 patient interviews, six key informant
      interviews, and two patient focus group discussions for investigating the reasons
      for default at the KC Patty Primary Health Centre and surrounding villages in
      Kodaikanal Taluk, Dindigul district, Tamil Nadu. The reasons included money or
      transport difficulties, frequent travel, feeling healthy, focus on work, fear of
      scolding from clinic staff, medication side effects, preference for alternative
      therapy, and depression. Some reasons were only divulged after an extended
      discussion. Support from families and village-level health workers (VLHWs) were
      also identified as important. Recommendations include more open and patient
      communication between health workers and defaulting patients, in addition to
      recruitment of more VLHWs. 

PMID- 24125935
TI  - Evaluation of adjustment methods used to determine prevalence of low birth-weight
      babies at a rural hospital in Andhra Pradesh, India.
AB  - Accurate reporting of prevalence of low birth weight (LBW) is important for
      monitoring health of a population. LBW is often underestimated in developing
      countries due to heaping of the data at 2.5 kg. UNICEF uses an average adjustment
      factor of 25% to re-classify babies listed as exactly 2.5 kg into the LBW
      category. From October 2009 to February 2010, we weighed 859 consecutive live
      births at a rural hospital in Andhra Pradesh, India, using analog and digital
      scales to evaluate the relative validity of the adjustment factor. Significantly
      more babies weighed exactly 2.5 kg on analog (13.4%) versus digital (2.2%)
      scales, showing heaping. Percentage of LBW by digital method (29.5%) was
      significantly higher compared to the analog method (23%) and with adjustment
      factors (26.4%). Conventional methods of adjusting birth-weight data
      underestimate the prevalence of LBW. Sensitive digital weighing machines or
      better adjustment methods are needed to monitor LBW in developing countries. 

PMID- 24125936
TI  - The effect of the lunar cycle on frequency of births: our experience in Peru.

PMID- 24125937
TI  - Rickettsiosis: a cause of acute febrile illness and value of Weil-Felix test.

PMID- 24125938
TI  - Indigenous medicines: a wake-up slap.

PMID- 24125939
TI  - Metastatic melanoma of the ovary and circulating S100B.

PMID- 24125940
TI  - Evaluation of the effects of ozone on yield of Japanese rice (Oryza sativa L.)
      based on stomatal ozone uptake.
AB  - To evaluate the negative impact of ozone (O3) on Japanese crop plant yield based
      on cumulative stomatal O3 flux, a Japanese rice cultivar, Koshihikari, was
      exposed to O3 in O3-exposure chambers. Stomatal diffusive conductance to water
      vapour were measured during the experimental period. We parameterized and
      improved a stomatal diffusive conductance model by considering seasonal changes
      in stomatal diffusive conductance, as well as the acute effects of O3 on this
      variable. Our adjusted model accounted for 64% of the variation within the data
      set. Based on the results of linear regression analyses of the relationship
      between relative yield and cumulative O3 uptake, the negative impact of O3 on the
      yield of Koshihikari can be evaluated using cumulative O3 uptake with a threshold
      of 10 nmol O3 m(-2) projected leaf area s(-1) and an integration period of -300
      to 100  degrees C days from anthesis. 

PMID- 24125941
TI  - Acyltransferases and transacylases that determine the fatty acid composition of
      glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells
      and model organisms.
AB  - Over one hundred different phospholipid molecular species are known to be present
      in mammalian cells and tissues. Fatty acid remodeling systems for phospholipids
      including acyl-CoA:lysophospholipid acyltransferases, CoA-dependent and CoA
      independent transacylation systems, are involved in the biosynthesis of these
      molecular species. Acyl-CoA:lysophospholipid acyltransferase system is involved
      in the synthesis of phospholipid molecular species containing sn-1 saturated and
      sn-2 unsaturated fatty acids. The CoA-dependent transacylation system catalyzes
      the transfer of fatty acids esterified in phospholipids to lysophospholipids in
      the presence of CoA without the generation of free fatty acids. The CoA-dependent
      transacylation reaction in the rat liver exhibits strict fatty acid specificity,
      i.e., three types of fatty acids (20:4, 18:2 and 18:0) are transferred. On the
      other hand, CoA-independent transacylase catalyzes the transfer of C20 and C22
      polyunsaturated fatty acids from diacyl phospholipids to various
      lysophospholipids, especially ether-containing lysophospholipids, in the absence
      of any cofactors. CoA-independent transacylase is assumed to be involved in the
      accumulation of PUFA in ether-containing phospholipids. These enzymes are
      involved in not only the remodeling of fatty acids, but also the synthesis and
      degradation of some bioactive lipids and their precursors. In this review, recent
      progresses in acyltransferase research including the identification of the
      enzyme's genes are described. 

PMID- 24125942
TI  - Family presence at bedside rounds in the intensive care unit: should we look at
      alternative solutions?

PMID- 24125943
TI  - A rapidly evolving revolution in stem cell biology and medicine.
AB  - The developments arising from human IVF are remarkable. Embryos were studied for
      developmental patterns that have consequences for viability and fertility.
      Growing human blastocysts in vitro allowed further exploration of the
      differentiation of primitive embryonic cells, leading to the discovery of human
      embryonic stem cells (ESC). The availability of perhaps unlimited numbers of
      human ESC could inform the study of differentiation and also provide cells for
      therapies in human regenerative medicine. The developments in cell biology have
      been impressive, including the discovery of induced pluripotent stem cells -
      adult cells transduced by specific transcription factors to behave like human
      ESC. Key regulators of development such as activators or inhibitors of lineage
      progression have also been explored, particularly the fibroblast growth factor,
      Wnt and transforming growth factor beta signalling pathways and miRNA. Such
      regulators can be utilized in algorithms to predict how cells differentiate in
      vitro. Using multistep differentiation protocols, many different cell types can
      be formed and matured into functionally effective cells, some of which are
      already in translational research for clinical applications. Possible future
      developments include destruction of cancer stem cells, reversal of type I
      diabetes, restoration of vision, repair of motor function, cure for HIV/AIDS and
      heart muscle regeneration.

PMID- 24125944
TI  - Neonatal and neurodevelopmental outcome of children aged 3-10 years born
      following assisted oocyte activation.
AB  - Assisted oocyte activation (AOA) using a calcium ionophore has been used for more
      than a decade following intracytoplasmic sperm injection (ICSI) fertilization
      failure. However, since AOA does not mimic precisely the physiological
      fertilization process, concerns exist about its use in human assisted
      reproduction. This study assessed the neonatal and neurodevelopmental outcome of
      children aged >= 3 years who had been born following AOA in our centre. Twenty
      one children participated in the study (81% response rate; mean age 63.6 +/-
      21.07 months). Neonatal data were collected via questionnaires.
      Neurodevelopmental outcome was tested using the Reynell Developmental Language
      Scales or Clinical Evaluation of Language Fundamentals, Wechsler Preschool and
      Primary Scale of Intelligence or Wechsler Intelligence Scale for Children, and
      the Movement Assessment Battery for Children III. Behaviour was scored by the
      Social Communication Questionnaire, the Child Behaviour Checklist and the
      Teachers Report Form. For all tests and questionnaires, the mean outcomes lay
      within the expected ranges. These are first data on the developmental outcome of
      AOA children. The high response rate and the robustness of the tests support the
      data, which are reassuring although still considered preliminary. Therefore, AOA
      should still be performed only in selected couples.

PMID- 24125945
TI  - Aspirin to improve IVF unexplained implantation rates: time for an individualized
      approach.

PMID- 24125946
TI  - Maternal control of genomic imprint maintenance.
AB  - Genomic imprinting is a specialized transcriptional phenomenon that employs
      epigenetic mechanisms to facilitate parental-specific expression. Perturbations
      in parental epigenetic asymmetry can lead to the development of imprinting
      disorders, such as Beckwith-Wiedemann syndrome and Angelman syndrome. DNA
      methylation is one of the most widely studied epigenetic marks that characterizes
      imprinted regions. During gametogenesis and early embryogenesis, imprinted
      methylation undergoes a cycle of erasure, acquisition and maintenance. Gamete and
      embryo manipulations for the purpose of assisted reproduction are performed
      during these reprogramming events and may lead to their disruption. Recent
      studies point to the role of maternal-effect proteins in imprinted gene
      regulation. Studies are now required to increase understanding of how these
      factors regulate genomic imprinting as well as how assisted reproduction
      technologies may alter their function.

PMID- 24125947
TI  - Decreased expression of Wiskott-Aldrich syndrome protein family verprolin
      homologous protein 2 may be involved in the development of pre-eclampsia.
AB  - Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) is
      a protein that mediates actin cytoskeletal reorganization and lamellipodia
      protrusion formation, which are required for cell migration and invasion. The
      primary purpose of this study was to determine whether there is an association
      between reactive oxygen species (ROS) and WAVE2 in pre-eclampsia, and whether
      WAVE2 expression in trophoblast cells is vulnerable to oxidative stress. This
      study observed excessive generation of ROS and decreased expression of WAVE2 in
      pre-eclamptic placentas compared with normotensive controls. Moreover, there was
      a significant negative correlation between ROS and WAVE2 protein in pre-eclamptic
      placenta (P < 0.001). An in-vitro model of hypoxia-reoxygenation (H/R) was used
      to imitate oxidative stress in placental trophoblasts, and it was found that the
      expression of WAVE2 protein in trophoblasts was decreased after H/R treatment.
      Additionally, compared with normoxia, decreased cell proliferation, higher cell
      apoptosis and attenuated cell migration and invasion were detected in
      trophoblasts exposed to H/R. In conclusion, the findings strongly suggest that
      excessive oxidative stress can decrease WAVE2 expression in trophoblasts and that
      the decreased expression of WAVE2 in trophoblast cells may be involved in the
      development of pre-eclampsia.

PMID- 24125949
TI  - Response to "What is the optimal approach to major ABO-incompatible allogeneic
      stem cell transplantation".

PMID- 24125950
TI  - Biological networks 101: computational modeling for molecular biologists.
AB  - Computational modeling of biological networks permits the comprehensive analysis
      of cells and tissues to define molecular phenotypes and novel hypotheses.
      Although a large number of software tools have been developed, the versatility of
      these tools is limited by mathematical complexities that prevent their broad
      adoption and effective use by molecular biologists. This study clarifies the
      basic aspects of molecular modeling, how to convert data into useful input, as
      well as the number of time points and molecular parameters that should be
      considered for molecular regulatory models with both explanatory and predictive
      potential. We illustrate the necessary experimental preconditions for converting
      data into a computational model of network dynamics. This model requires neither
      a thorough background in mathematics nor precise data on intracellular
      concentrations, binding affinities or reaction kinetics. Finally, we show how an
      interactive model of crosstalk between signal transduction pathways in primary
      human articular chondrocytes allows insight into processes that regulate gene
      expression. 

PMID- 24125951
TI  - Sexual differences of imprinted genes' expression levels.
AB  - In mammals, genomic imprinting has evolved as a dosage-controlling mechanism for
      a subset of genes that play critical roles in their unusual reproduction scheme
      involving viviparity and placentation. As such, many imprinted genes are highly
      expressed in sex-specific reproductive organs. In the current study, we sought to
      test whether imprinted genes are differentially expressed between the two sexes.
      According to the results, the expression levels of the following genes differ
      between the two sexes of mice: Peg3, Zim1, Igf2, H19 and Zac1. The expression
      levels of these imprinted genes are usually greater in males than in females.
      This bias is most obvious in the developing brains of 14.5-dpc embryos, but also
      detected in the brains of postnatal-stage mice. However, this sexual bias is not
      obvious in 10.5-dpc embryos, a developmental stage before the sexual
      differentiation. Thus, the sexual bias observed in the imprinted genes is most
      likely attributable by gonadal hormones rather than by sex chromosome complement.
      Overall, the results indicate that several imprinted genes are sexually different
      in terms of their expression levels, and further suggest that the transcriptional
      regulation of these imprinted genes may be influenced by unknown mechanisms
      associated with sexual differentiation. 

PMID- 24125952
TI  - Transcriptome analysis of Capsicum annuum varieties Mandarin and Blackcluster:
      assembly, annotation and molecular marker discovery.
AB  - Next generation sequencing technologies have proven to be a rapid and cost
      effective means to assemble and characterize gene content and identify molecular
      markers in various organisms. Pepper (Capsicum annuum L., Solanaceae) is a major
      staple vegetable crop, which is economically important and has worldwide
      distribution. High-throughput transcriptome profiling of two pepper cultivars,
      Mandarin and Blackcluster, using 454 GS-FLX pyrosequencing yielded 279,221 and
      316,357 sequenced reads with a total 120.44 and 142.54Mb of sequence data
      (average read length of 431 and 450 nucleotides). These reads resulted from
      17,525 and 16,341 'isogroups' and were assembled into 19,388 and 18,057 isotigs,
      and 22,217 and 13,153 singletons for both the cultivars, respectively. Assembled
      sequences were annotated functionally based on homology to genes in multiple
      public databases. Detailed sequence variant analysis identified a total of 9701
      and 12,741 potential SNPs which eventually resulted in 1025 and 1059 genotype
      specific SNPs, for both the varieties, respectively, after examining SNP
      frequency distribution for each mapped unigenes. These markers for pepper will be
      highly valuable for marker-assisted breeding and other genetic studies. 

PMID- 24125953
TI  - Extraordinarily low evolutionary rates of short wavelength-sensitive opsin
      pseudogenes.
AB  - Aquatic organisms such as cichlids, coelacanths, seals, and cetaceans are active
      in UV-blue color environments, but many of them mysteriously lost their abilities
      to detect these colors. The loss of these functions is a consequence of the
      pseudogenization of their short wavelength-sensitive (SWS1) opsin genes without
      gene duplication. We show that the SWS1 gene (BdenS1psi) of the deep-sea fish,
      pearleye (Benthalbella dentata), became a pseudogene in a similar fashion about
      130 million years ago (Mya) yet it is still transcribed. The rates of nucleotide
      substitution (~1.4 * 10(-9)/site/year) of the pseudogenes of these aquatic
      species as well as some prosimian and bat species are much smaller than the
      previous estimates for the globin and immunoglobulin pseudogenes.

PMID- 24125954
TI  - Identifier (ID) elements are not preferentially located to brain-specific genes:
      high ID element representation in other tissue-specific- and housekeeping genes
      of the rat.
AB  - BC1 is a short non-coding RNA from rodents, which is transcribed by RNA pol III.
      Its RNA is highly abundant in the brain, where it exerts a post-transcriptional
      regulatory role in dendrites. Upon transcription, retroposition and insertion,
      BC1 gives rise to a subclass of short interspersed repetitive sequences (SINEs)
      named identifier (ID) elements. IDs can become integrated inside non-coding
      regions of RNA pol II transcription units, and - although challenged by a couple
      of reports - their preferential location to brain-specific genes has been long
      proposed. Furthermore, an additional, cis-regulatory role in the control of brain
      specific pol II-directed transcripts has been suggested for these sequences. In
      this work we used Northern blot and in silico analyses to examine IDs' location
      among pol II transcription units in different tissues, and in housekeeping genes.
      ID sequences appeared distributed in a similar fashion within tissue-specific
      hnRNA populations of the brain, testis and liver, and within housekeeping primary
      transcripts as well. Moreover, when the lengths of the unprocessed transcripts
      were considered, ID representation was higher in housekeeping ones. On the other
      hand, ID elements appeared similarly distributed among the different gene
      regions, with the obvious exclusion of those sequences where strict constraints
      for proper gene expression exist. Altogether, the widespread distribution of ID
      elements in all the analyzed genes - including housekeeping - and in all gene
      regions, suggests a random location, raising questions about the specific cis
      regulatory role of those sequences. 

PMID- 24125955
TI  - Axis-matching excitation pulses for CPMG-like sequences in inhomogeneous fields.
AB  - The performance of the standard CPMG sequence in inhomogeneous fields can be
      improved with the use of broadband excitation and refocusing pulses. Here we
      introduce a new class of excitation pulses, so-called axis-matching excitation
      pulses, that optimize the response for a given refocusing pulse. These new
      excitation pulses are tailored to the refocusing pulses and take their
      imperfections into account. Rather than generating purely transverse
      magnetization, these pulses are designed to generate magnetization pointing along
      the axis of the effective rotation of the refocusing cycle. This approach
      maximizes the CPMG component and minimizes the CP component of the signal.
      Replacing a standard 90 degrees  pulse with a new excitation pulse matched to the
      180 degrees  refocusing pulse increases the signal bandwidth and improves the
      echo amplitudes by 30% in inhomogeneous fields in comparison to the standard CPMG
      sequence. Larger gains are obtained with more advanced refocusing pulses. Recent
      work demonstrated that it is possible to increase the signal to noise ratio (SNR)
      of individual echoes by more than a factor of 1.5 (in power units) without
      increasing the duration or amplitude of the refocusing pulses. This was achieved
      by replacing the standard 180 degrees  refocusing pulse by a short phase
      alternating pulse and the standard 90 degrees  excitation pulse by a broadband
      excitation pulse. We show here that with suitable axis-matching excitation
      pulses, the SNR further increases by over a factor of 2. We discuss the
      underlying theory and present several practical implementations of purely phase
      modulated axis-matching excitation pulses for a number of different refocusing
      pulses that were derived using methods of optimal control. To gain the full
      benefit of these new excitation pulses, it is essential to replace the standard
      phase cycling scheme based on 180 degrees  phase shifts by a new scheme involving
      phase inversion. We tested the new pulses experimentally and observe excellent
      agreement with the theoretical expectations. We also demonstrate that an
      additional benefit of axis-matching excitation pulses is the decrease of the
      transient that appears in the amplitudes of the first few echoes, thus enabling
      better measurements of short relaxation times. 

PMID- 24125956
TI  - Estimation of spin-echo relaxation time.
AB  - In spin-echo-based EPR oximetry, traditional methods to estimate the T2
      relaxation time, which encodes the oxygen concentration of the sample, include
      fitting an exponential to the peaks or the integrated areas of multiple noisy
      echoes. These methods are suboptimal and result in a loss of estimation precision
      for a given acquisition time. Here, we present the maximum likelihood estimate
      (MLE) of T2 from spin-echo data. The MLE provides, for the data considered,
      approximately 3-fold time savings over echo-integration and more than 40-fold
      time savings over peak-picking. A one-dimensional line search results in simple
      computation of the MLE. It is observed that, perhaps counter-intuitively, prior
      knowledge of the lineshape does not yield additional reduction of estimation
      error variance at practical noise levels. The result also illuminates the near
      optimal performance of T2 estimation via principal components calculated by a
      singular value decomposition. The proposed method is illustrated by application
      to simulated and experimental EPR data. 

PMID- 24125958
TI  - Topographies of forensic practice in Imperial Germany.
AB  - This article examines the topography and "cultural machinery" of forensic
      jurisdictions in Imperial Germany. It locates the sites at which boundary
      disputes between psychiatric and legal professionals arose and explores the
      strategies and practices that governed the division of expert labor between them.
      It argues that the over-determined paradigms of 'medicalization' and
      'biologization' have lost much of their explanatory force and that historians
      need to refocus their attention on the institutional and administrative
      configuration of forensic practices in Germany. After first sketching the
      statutory context of those practices, the article explores how contentious
      jurisdictional negotiations pitted various administrative, financial, public
      security, and scientific interests against one another. The article also assesses
      the contested status of psychiatric expertise in the courtroom, as well as post
      graduate forensic psychiatric training courses and joint professional
      organizations, which drew the two professional communities closer together and
      mediated their jurisdictional disputes.

PMID- 24125957
TI  - Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar
      cells by restricting competence.
AB  - During retinal development, photoreceptors and bipolar cells express the
      transcription factor Otx2. Blimp1 is transiently expressed in Otx2+ cells. Blimp1
      deletion results in excess bipolar cell formation at the expense of
      photoreceptors. In principle, Blimp1 could be expressed only in Otx2+ cells that
      are committed to photoreceptor fate. Alternatively, Blimp1 could be expressed
      broadly in Otx2+ cells and silenced to allow bipolar cell development. To
      distinguish between these alternatives, we followed the fate of Blimp1 expressing
      cells using Blimp1-Cre mice and Lox-Stop-Lox reporter strains. We observed that
      Blimp1+ cells gave rise to all photoreceptors, but also to one third of bipolar
      cells, consistent with the latter alternative: that Blimp1 inhibits bipolar
      competence in Otx2+ cells and must be silenced to allow bipolar cell generation.
      To further test this hypothesis, we looked for transitioning rod photoreceptors
      in Blimp1 conditional knock-out (CKO) mice carrying the NRL-GFP transgene, which
      specifically labels rods. Control animals lacked NRL-GFP+ bipolar cells. In
      contrast, about half of the precociously generated bipolar cells in Blimp1 CKO
      mice co-expressed GFP, suggesting that rods become re-specified as bipolar cells.
      Birthdating analyses in control and Blimp1 CKO mice showed that bipolar cells
      were birthdated as early as E13.5 in Blimp1 CKO mice, five days before this cell
      type was generated in the wild-type retina. Taken together, our data suggest that
      early Otx2+ cells upregulate photoreceptor and bipolar genes, existing in a
      bistable state. Blimp1 likely forms a cross-repressive network with pro-bipolar
      factors such that the winner of this interaction stabilizes the photoreceptor or
      bipolar state, respectively. 

PMID- 24125959
TI  - Forensic psychiatric units in Italy from the 1960s to the present.
AB  - This article addresses the long-standing continuities in the history of the
      Italian forensic psychiatric units and views them as the result of conflicting
      forces, interests, mentalities and strategies at the cross-road of forensic
      psychiatry, psychiatry, prison and health services. It focuses on the period from
      the 1960s to the present and deals with, among other issues, the long-term impact
      of the anti-asylum movements and the on-going debate on the 'phasing out' of the
      forensic psychiatric units.

PMID- 24125960
TI  - Quebec proposition of Medical Aid in Dying: a palliative care perspective.
AB  - The government of Quebec (Canada) is poised to adopt a proposition to legalize
      euthanasia in the form of "Medical Aid in Dying," which presents a new option for
      end-of-life care. This proposition arouses concerns among palliative care
      providers. The aim of this article is to provide a palliative care perspective on
      Quebec's proposition to legalize euthanasia. Based on the epistemological and
      methodological framework of critical theory, the following three questions are
      raised: First, in Quebec's current state of the law, is it possible to relieve
      the suffering of end-of-life patients? Second, can the Quebec proposition to
      legalize euthanasia in specific circumstances be harmful? Third, is the Quebec
      proposition on euthanasia compatible with palliative care and social values? In
      conclusion, recommendations and alternatives to the current Quebec proposition
      are suggested. 

PMID- 24125961
TI  - Effects of EPHX1, SCN1A and CYP3A4 genetic polymorphisms on plasma carbamazepine
      concentrations and pharmacoresistance in Chinese patients with epilepsy.
AB  - The pharmacokinetics and pharmacodynamics of carbamazepine (CBZ) vary widely
      among patients with epilepsy. In this study, we sought to investigate the effects
      of genetic polymorphisms of the microsomal epoxide hydrolase (EPHX1), the sodium
      channel alpha subunit type I (SCN1A) and the cytochrome P450 3A4 (CYP3A4) genes
      on plasma CBZ concentrations and pharmacoresistance in Chinese patients with
      epilepsy. The EPHX1 c.337T>C, c.416A>G, SCN1A IVS5-91G>A or CYP3A4*1G
      polymorphisms were detected by polymerase chain reaction-restriction fragment
      length polymorphism approach or direct DNA sequencing in 83 Chinese patients
      treated with CBZ monotherapy. Patients with the variant EPHX1 c.416A>G genotypes
      had higher adjusted plasma CBZ concentrations compared to those with the wild
      type genotype (P<0.05). In contrast, the SCN1A IVS5-91G>A and CYP3A4*1G variant
      alleles had no significant effects on CBZ maintenance doses or adjusted CBZ
      concentrations. There were no associations between all the studied genotypes
      involving EPHX1 c.337T>C, c.416A>G, SCN1A IVS5-91G>A or CYP3A4*1G polymorphisms
      and pharmacoresistance in this patient cohort. These results suggest that the
      EPHX1 c.416A>G polymorphism affects CBZ metabolism in Chinese patients with
      epilepsy. However, whether it contributes to CBZ resistance needs to be further
      investigated in a larger cohort of patients. 

PMID- 24125962
TI  - Inheritance of maladies and the gene fairy.

PMID- 24125963
TI  - Sacrococcygeal neoplastic lesions.
AB  - Sacrococcygeal neoplastic lesions are very rare entities and therefore, a
      diagnostic and therapeutic challenge. They include developmental cysts,
      inflammatory, neurogenic, osseous and miscellaneous lesions. In this review, we
      discuss the incidence, symptoms, characteristics, diagnostic methods and
      treatment strategies of these enigmatic lesions. We have to highlight the high
      index of suspicion that is necessary when dealing with chronic sacrococcygeal
      pain or multiple perianal abscesses or persistent perianal drainage, because any
      misinterpretation may result in unfavorable outcomes.

PMID- 24125964
TI  - Fractionated beam radiotherapy is a special case of continuous beam radiotherapy
      when irradiation time is small.
AB  - Fractionated beam radiotherapy, in other terms, external beam radiotherapy (EBRT)
      and continuous beam radiotherapy or Brachytherapy are two modes of radiotherapy
      techniques. Although in many ways, they appear to be different,
      radiobiologically, with the help of mathematics, it can be proved that the
      biological effective dose (BED) of EBRT is similar to BED of Brachytherapy, when
      irradiation time is small. Here an attempt is made to correlate these two
      predominant modes of radiotherapy techniques.

PMID- 24125965
TI  - Use of microwave in diagnostic pathology.
AB  - Conventional tissue fixation and processing is as old as 100 years and still
      remains the gold standard against which all new technologies and methods need to
      be assessed. Tissue processing is one of the important steps for obtaining good
      thin sections without artifacts. Though conventional tissue-processing methods
      are most commonly followed, they are well-known as very laborious and tedious
      procedures. Microwaves a form of electromagnetic wave-induced heat, when applied
      in histotechnology, reproducibly yields histolologic material of similar or
      superior quality to that provided by conventional processing methods, making it
      more popular in the recent years. A laboratory microwave offers features like
      maximum output of 2000-3000 watts, an in-built source of adjustable temperature
      probe, facility for ventilation of hazardous fumes, but is expensive. Considering
      the usefulness of microwave in histotechnology, i.e., reducing the time required
      for the diagnosis, replacing the conventional equipments of laboratories by
      microwave-guided ones is a remarkable and an acceptable change.

PMID- 24125966
TI  - Matrix metalloproteinases and their tissue inhibitors in gastric cancer as
      molecular markers.
AB  - Gastric cancer is a complex disease that involves a range of biological
      individuals and tumors with histopathological features. The pathogenesis of this
      disease is multi-factorial and includes the interaction of genetic predisposition
      with environmental factors. Gastric cancer is normally diagnosed in advanced
      stages where there are few alternatives to offer and the prognosis is difficult
      to establish. Metastasis is the leading cause of cancer deaths. Identification of
      key genes and signaling pathways involved in metastasis and recurrence could
      predict these events and thereby identify therapeutic targets. In this context,
      the extracellular matrix metalloproteinases (MMPs) and their inhibitors (TIMPs)
      represent a potential prognostic tool, because both genetic families regulate
      growth, angiogenesis, invasion, immune response, epithelial mesenchymal
      transition and cellular survival. Proteolytic parameters based on MMP/TIMP
      expression could be useful in the identification of patients with a high
      probability of developing distant metastases or peritoneal dissemination for each
      degree of histological malignancy. It is also probable that these parameters can
      allow improvement in the extent of surgery and dictate the most suitable therapy.
      We reviewed papers focused on human gastric epithelial cancer as a model and
      focus on the potential use of MMPs and TIMPs as molecular markers; also we
      include literature regarding gastric cancer risk factors, classification systems
      and MMP/TIMP regulation.

PMID- 24125967
TI  - Ascorbic acid glucoside reduces neurotoxicity and glutathione depletion in mouse
      brain induced by nitrotriazole radiosensitazer.
AB  - AIM: To investigate the potential of the anti-oxidant ascorbic acid glucoside (AA
      2G) to modulate neurotoxicity induced by high doses of nitrotriazole
      radiosensitizer. MATERIALS AND METHODS: Male and female C56Bl/6xCBA hybrid mice
      aged 8-14 weeks (weight 18-24 g) were used. Nitrotriazole drug radiosensitizer
      sanazole at a high dose of 2, 1 g/kg was per os administered to induce
      neurotoxicity at mice. Ascorbic acid glucoside was given 30 min before the
      sanazole administration. Serum ascorbic acid, brain glutathione level, as well as
      behavioral performance using open field apparatus were measured. RESULTS:
      Administration of high (non-therapeutic) doses of the nitrotriazole drug sanazole
      results in neurotoxicity in mice as evidenced from behavioral performance,
      emotional activity and depletion of the cellular antioxidant, glutathione, in the
      brain. The serum levels of ascorbic acid was also found reduced in high dose
      sanazole treated animals. Per os administration of ascorbic acid glucoside
      significantly reduced the neurotoxicity. This effect was associated with the
      prevention of glutathione depletion in mouse brain and restoring the ascorbic
      acid level in serum. CONCLUSION: Administration of ascorbic acid glucoside, but
      not ascorbic acid, before sanazole administration protected from sanazole-induced
      neurotoxicity by preventing the decrease in the brain reduced glutathione level
      and providing high level of ascorbic acid in plasma.

PMID- 24125969
TI  - Aberrant expression of trefoil factor 3 is associated with colorectal carcinoma
      metastasis.
AB  - BACKGROUND: Recent evidence has indicated that the trefoil factor family
      possesses pivotal roles in the progression of human cancer. Aberrant expression
      of trefoil factor 3 (TFF3) has been reported to correlate with an aggressive
      tumor phenotype. However, the clinical importance of TFF3 expression in
      colorectal carcinomas (CRCs) has rarely been addressed. PURPOSE: To investigate
      the putative role of TFF3 in colorectal carcinogenesis and progress, and to
      clarify whether TFF3 could be a serum marker for CRCs. MATERIALS AND METHODS:
      Fifty-six CRCs were sequenced for TFF3 mutations; subsets of the primary tumors
      were subjected to real-time quantitative reverse transcription polymerase chain
      reaction (RT-PCR) and immunohistochemistry analyses and serum TFF3 was detected
      by enzyme-linked immunosorbent assay (ELISA) for patients with CRCs. RESULTS: No
      variants were detected in the code area of TFF3; TFF3 mRNA is increased in CRCs
      but not up to statistic significance when compared with paired normal colonic
      mucosa; TFF3 staining by immunohistochemistry in primary CRCs showed that
      increased expression of TFF3 is associated with lymph node metastases(LNM), and
      no significant differences were found with respect to patient's sex, cancer cell
      differentiation and stage. Serum TFF3 is significantly elevated in patients with
      CRCs, especially CRCs with LNM. CONCLUSION: The results indicate that TFF3 point
      mutations seem to be a rare event in colorectal carcinogenesis; TFF3 expression
      may play a role in promoting lymph node metastases of CRCs and serum TFF3 may be
      a potential useful marker for patients with CRCs and their metastases.

PMID- 24125968
TI  - An investigation of the effects of FGFR2 and B7-H4 polymorphisms in breast
      cancer.
AB  - INTRODUCTION: Polymorphisms in FGFR2 are important markers for breast cancer
      susceptibility in the general population. CHEK2 and FGFR2 polymorphisms with
      known susceptibility alleles of BRCA1, BRCA2, PTEN, and TP53, can be investigated
      as potential modifiers of high penetrant risk alleles. Although the B7-H4 gene is
      highly expressed in many different tumors, there is one published study showing
      the association of polymorphisms with breast cancer. We aimed to investigate
      FGFR2 and B7-H4 polymorphisms in breast cancer in the Turkish community.
      MATERIALS AND METHODS: In a group of 31 cases diagnosed with breast cancer and 30
      healthy women with matched ages, the single-nucleotide polymorphisms (SNPs)
      rs1219648, rs2981582 in FGFR2 gene were identified by sequence analysis and the
      SNPs rs10754339, rs10801935, and rs3738414 in the B7-H4 gene were identified by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Statistical analysis was performed using SPSS. RESULTS: Although
      statistically not significant, the frequency of FGFR2 heterozygous polymorphisms
      in the group with breast cancer was detected to be higher. In the B7-H4 SNP
      rs10801935, polymorphic AA, and AG genotype distributions were found in higher
      frequencies in the breast cancer patients. In contrast to the results of a
      published study, the present study shows that B7-H4 rs3738414 polymorphism GG
      genotype was found in higher frequency in the control group than the breast
      cancer group and the result was statistically significant (P=0.018). CONCLUSION:
      Larger scale studies are necessary to determine the prevalence of these
      polymorphisms and association with breast cancer in Turkish community, as this
      study is the first study performed.

PMID- 24125970
TI  - Postoperative treatment of glioblastoma multiforme with radiation therapy plus
      concomitant and adjuvant temozolomide : A mono-institutional experience of 215
      patients.
AB  - OBJECTIVE: To study the clinical results and prognostic factors of patients with
      glioblastoma multiforme (GBM) treated by postoperative radiation therapy (PORT)
      and concomitant temozolomide followed by adjuvant temozolomide. METHODS: From
      2005 to 2008, 215 patients (median age 48 years) with GBM were treated with PORT
      plus temozolomide chemotherapy. Radiation therapy (RT) was employed with a dose
      of 60 Gy in 30 fractions over 6 weeks by conventional fractionation with
      concomitant temozolomide (75 mg/m(2)/day). Adjuvant therapy consisted of 6 cycles
      of temozolomide (150 mg/m(2) for 5 days, 28 days cycle). The primary end point of
      the study was overall survival (OS), and the secondary end points were
      progression free survival (PFS) and toxicity. OS was determined with respect to
      different variables to study the prognostic significance. RESULTS: Median follow
      up was 11 months (range 2-50 months). Median OS and PFS were 13 months and 11
      months respectively. The 1-year and 2-year OS was 44% and 18% respectively. There
      was no statistical significant impact of age, sex, KP score, anatomical location
      and extent of surgery. Presentation without seizures (on univariate analysis) and
      6 cycles of adjuvant temozolomide therapy (on univariate as well as multivariate
      analysis) were found significant prognostic factors. Sixteen patients developed
      grade III-IV neutropenia/thrombocytopenia during the course of RT. CONCLUSION:
      Our results authenticate the role of concomitant and adjuvant temozolomide
      chemotherapy in combination with PORT for the management of GBM patients. We
      strongly recommend complete 6 cycle of adjuvant temozolomide since it
      significantly improved the survival in our study.

PMID- 24125971
TI  - The role of mast cells and angiogenesis in well-differentiated oral squamous cell
      carcinoma.
AB  - OBJECTIVE: Neo-vascularization is vital for an expansion and metastasis of a
      tumor and is influenced by a number of mediators. Mast cells are believed to
      release many pro-angiogenic mediators that may help in tumor expansion and
      invasion. This study describes the role of mast cells and angiogenesis in oral
      squamous cell carcinoma (OSCC). STUDY DESIGN: It was a prospective study in which
      37 biopsies of well-differentiated OSCC were obtained. Micro-vessels were stained
      with cluster of differentiation (CD)-34 and mast cells were counted using the
      Toluidine blue stain. RESULTS: When compared to normal oral mucosal tissue, it
      was seen that micro-vessel density and mast cell density indeed increases
      significantly in squamous cell carcinoma; however, they are not correlated to
      each other. CONCLUSION: This study reports that angiogenesis does increase in
      OSCC and mast cells also invade the peri-tumor tissue, but they are not directly
      correlated.

PMID- 24125972
TI  - Concurrent chemoradiation with weekly cisplatin, docetaxel and gefitinib: A study
      to assess feasibility, toxicity and immediate response.
AB  - OBJECTIVES: Addition of docetaxel in the treatment regimen has shown improvement
      in survival of head and neck squamous cell carcinoma (HNSCC) patients. This study
      was conducted to evaluate the maximum tolerated dose of weekly docetaxel when
      combined with concurrent administration of weekly cisplatin, daily gefitinib, and
      radiation therapy. MATERIALS AND METHODS: 21 patients with newly diagnosed HNSCC
      were included. Radiation therapy was planned to a dose of 66 Gy/33 fractions.
      Doses of cisplatin and gefitinib were kept constant at 30 mg/m(2) and 250 mg
      respectively. Dose of weekly docetaxel started with 5 mg/m(2) and escalated 5
      mg/m(2) up to a maximum of 20 mg/m 2 . Serious adverse event was defined as grade
      3/4 hematological and non-hematological toxicities. RESULTS: All patients (three
      in dose level 1 [5 mg/m(2)], level 2 [10 mg/m(2)] and level 3 [15 mg/m(2)]) did
      not experience any hematological serious adverse events. Weekly docetaxel of 20
      mg/m(2) could not be tolerated with the combination, and we encountered two
      hematological (neutropenia) serious grade 4 adverse event and one grade 3
      mucositis at level 4. Six patients were treated by omitting week 3 chemotherapy
      reducing the number of weekly cycles to a minimum of four. Gefitinib was
      continued throughout the treatment period. All patients tolerated the treatment
      well although with grade 2 hematological/non hematological toxicities.
      CONCLUSION: The maximal tolerated dose of weekly docetaxel added to weekly
      cisplatin and daily gefitinib during concurrent chemoradiation is 15 mg/m(2).
      Toxicity profile is tolerable with a break in the chemotherapy regimen during
      radiation therapy. Aggressive nutritional support is essential prior to this
      regimen.

PMID- 24125973
TI  - Cost analysis of in-patient cancer chemotherapy at a tertiary care hospital.
AB  - AIM: Cancer remains a major health problem in all communities worldwide. Rising
      healthcare costs associated with treating advanced cancers present a significant
      economic challenge. It is a need of the hour that the health sector should devise
      cost-effective measures to be put in place for better affordability of
      treatments. To achieve this objective, information generation through indigenous
      hospital data on unit cost of in-patient cancer chemotherapy in medical oncology
      became imperative and thus hallmark of this study. DESIGN AND SETTING: The
      present prospective hospital based study was conducted in Medical Oncology
      Department of tertiary care teaching hospital. MATERIALS AND METHODS: After
      permission from the Ethical Committee, a prospective study of 6 months duration
      was carried out to study the cost of treatment provided to in-patients in Medical
      Oncology. Direct costs that include the cost of material, labor and laboratory
      investigations, along with indirect costs were calculated, and data analyzed to
      compute unit cost of treatment. RESULTS: The major cost components of in-patient
      cancer chemotherapy are cost of drugs and materials as 46.88% and labor as
      48.45%. The average unit cost per patient per bed day for in-patient chemotherapy
      is Rs. 5725.12 ($125.96). This includes expenditure incurred both by the hospital
      and the patient (out of pocket). CONCLUSION: The economic burden of cancer
      treatment is quite high both for the patient and the healthcare provider.
      Modalities in the form of health insurance coverage need to be established and
      strengthened for pooling of resources for the treatment and transfer of risks of
      these patients.

PMID- 24125974
TI  - Dosimetric comparison between three dimensional treatment planning system, Monte
      Carlo simulation and gel dosimetry in nasopharynx phantom for high dose rate
      brachytherapy.
AB  - PURPOSE: For the treatment of nasopharnx carcinoma (NPC) using brachytherapy
      methods and high-energy photon sources are common techniques. In the common three
      dimensional (3D) treatments planning, all of the computed tomography images are
      assumed homogeneous. This study presents the results of Monte Carlo calculations
      for non-homogeneous nasopharynx phantom, MAGICA normoxic gel dosimetry and 3D
      treatment planning system (TPS). MATERIALS AND METHODS: The head phantom was
      designed with Plexiglas cylinder, head bone, and nasopharynx brachytherapy
      silicon applicator. For the simulations, version 5 of the Monte Carlo N-particle
      transport code (MCNP5) was used. 3D treatment planning was performed in Flexiplan
      software. A normoxic radiosensitive polymer gel was fabricated under normal
      atmospheric conditions and poured into test tubes (for calibration curve) and the
      head phantom. In addition, the head phantom was irradiated with Flexitron
      afterloader brachytherapy machine with (192)Ir source. To obtain calibration
      curves, 11 dosimeters were irradiated with dose range of 0-2000 cGy. Evaluations
      of dosimeters were performed on 1.5T scanner. RESULTS: Two-dimensional iso-dose
      in coronal plan at distances of z = +0.3, -0.3 cm was calculated. There was a
      good accordance between 3D TPS and MCNP5 simulation and differences in various
      distances were between 2.4% and 6.1%. There was a predictable accordance between
      MAGICA gel dosimetry and MCNP5 simulation and differences in various distances
      were between 5.7% and 7.4%. Moreover, there was an acceptable accordance between
      MAGICA gel dosimetry and MCNP5 data and differences in various distances were
      between 5.2% and 9.4%. CONCLUSION: The sources of differences in this comparison
      are divided to calculations variation and practical errors that was added in
      experimental dosimetry. The result of quality assurance of nasopharynx high dose
      rate brachytherapy is consistent with international standards.

PMID- 24125975
TI  - Excision repair cross-complementation group 1 codon 118 polymorphism, micro
      ribonucleic acid and protein expression, clinical outcome of the advanced gastric
      cancer response to first-line FOLFOX-4 in Qinghai-Tibetan plateau population.
AB  - CONTEXT: The excision repair cross-complementation group 1 (ERCC1) codon 118 C/T
      polymorphism has been associated with clinical outcome in cancer patients treated
      with platinum chemotherapy. Ethnic differences in the frequency of this
      polymorphism have been observed in Caucasian and African populations. AIM: The
      aim of this study was to evaluate the frequency and survival benefit of the ERCC1
      codon 118 C/T polymorphism in a high-altitude population with advanced gastric
      cancer. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment
      length polymorphism was used to determine the frequency of ERCC1 118 codon C/T
      polymorphism in 206 advanced gastric cancer patients residing in the high
      altitude Qinghai-Tibetan plateau. The influence of the ERCC1 codon 118 C/T
      polymorphism on its micro ribonucleic acid (mRNA) and protein expression,
      clinicopathological features; response to the platinum-based combination
      chemotherapy, and the outcome was evaluated. STATISTICAL ANALYSIS: The Kaplan
      Meier method was used for survival analysis. The correlation of ERCC1 codon 118
      polymorphism with ERCC1 mRNA and protein expression, clinicopathological
      characteristics, and first-line oxaliplatin, 5-fluorouracil, and leucovorin
      (FOLFOX-4) response was determined by chi(2)-test. RESULTS AND CONCLUSIONS: ERCC1
      codon 118 C/T polymorphism was not associated with ERCC1 mRNA and protein
      expression, FOLFOX-4 response, and progression-free survival (PFS) or overall
      survival (OS). High ERCC1 mRNA and protein expression levels were associated with
      significantly lower FOLFOX-4 responses, PFS, and OS. ERCC1 codon 118 C/T
      polymorphism is not an important prognostic marker for advanced gastric cancer.
      Determination of ERCC1 mRNA and protein levels may be beneficial in predicting
      the response and outcome of FOLFOX-4 therapy in gastric cancer.

PMID- 24125976
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration for the
      diagnosis of intrathoracic lymphadenopathy in patients with extrathoracic
      malignancy: A study in a tuberculosis-endemic country.
AB  - BACKGROUND: Mediastinal lymphadenopathy in patients with malignancy is a common
      clinical problem in tuberculosis-endemic countries. The recently developed
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
      procedure enables direct and real-time aspiration of mediastinal and hilar lymph
      nodes. The aim of the study was to determine the efficacy of EBUS-TBNA results in
      the evaluation of mediastinal lymph nodes in patients with extrathoracic
      malignancy. MATERIALS AND METHODS: Retrospective analysis was performed in 40
      patients with proven (n = 38) or suspected metastasis of unknown origin (n = 2)
      who underwent EBUS-TBNA between July 2007 and August 2011. RESULTS: All 40
      patients successfully underwent EBUS-TBNA and no complications were observed.
      EBUS-TBNA diagnosed metastasis from extrathoracic malignancy in 16 (40%)
      patients, new lung cancer in 2 (5%), reactive lymph node in 9 (22.5%),
      sarcoidosis in 5 (12.5%), anthracosis in 5 (12.5%) and tuberculosis in 3 (7.5%).
      The diagnostic sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV) and accuracy of EBUS-TBNA based on the number of
      patients were 90.0%, 100%, 100%, 90.9% and 95.0%, respectively. In 33 patients
      with available data of fluorodeoxyglucose positron emission tomography
      (PET)/computed tomography (CT) scans, the diagnostic sensitivity, specificity,
      PPV, NPV and accuracy of PET/CT scan based on the number of patients were 94.7%,
      35.7%, 66.6%, 83.3%, and 69.6%, respectively. The association between larger
      lymph node size on EBUS and malignancy of lymph node sample on pathological
      examination was statistically significant (P = 0.018). CONCLUSIONS: EBUS-TBNA is
      a sensitive, specific, minimally invasive and a safe procedure for the diagnosis
      of mediastinal and hilar metastasis from extrapulmonary malignancy in a
      tuberculosis-endemic country.

PMID- 24125977
TI  - Forward versus inverse planning in oropharyngeal cancer: A comparative study
      using physical and biological indices.
AB  - CONTEXT: Possible benefits of inverse planning. AIMS: To analyze possible
      benefits of inverse planning intensity modulated radiation therapy (IMRT) over
      field-in-field 3D conformal radiation therapy (FIF-3DCRT) and to evaluate the
      differences if any, between low (6 Million Volts) and high energy (15 Million
      Volts) IMRT plans. MATERIALS AND METHODS: Ten patients with squamous cell
      carcinoma of oropharynx, previously treated with 6 MV step and shoot IMRT were
      studied. V100, V33, V66 , mean dose and normal tissue complication probabilities
      (NTCP) were evaluated for parotid glands. Maximum dose and NTCP were the
      parameters for spinal cord. STATISTICAL ANALYSIS USED: A two-tailed t-test was
      applied to analyze statistical significance between the different techniques.
      RESULTS: For combined parotid gland, a reduction of 4.374 Gy, 9.343 Gy and 7.883
      Gy were achieved for D100, D66 and D33, respectively in 6 MV-IMRT when compared
      with FIF-3DCRT. Spinal cord sparing was better in 6 MV-IMRT (40.963 +/- 2.650),
      with an average reduction of maximum spinal cord dose by 7.355 Gy from that using
      the FIF-3DCRT technique. The uncomplicated tumor control probabilities values
      were higher in IMRT plans thus leading to a possibility of dose escalation.
      CONCLUSIONS: Though low-energy IMRT is the preferred choice for treatment of
      oropharyngeal cancers, FIF-3DCRT must be given due consideration as a second
      choice for its well established advantages over traditional conventioan
      technique.

PMID- 24125978
TI  - Dosimetric impact of Acuros XB dose calculation algorithm in prostate cancer
      treatment using RapidArc.
AB  - PURPOSE: The purpose of this study is to assess the dosimetric impact of Acuros
      XB dose calculation algorithm (AXB), in comparisons with Anisotropic Analytical
      Algorithm (AAA) calculations in prostate cancer treatment using RapidArc.
      MATERIALS AND METHODS: A computed tomography (CT) dataset of low-risk prostate
      cancer patients treated at Arizona Center for Cancer Care was selected and
      contoured for prostate, seminal vesicles, and organs at risk (OARs)(rectum,
      bladder, and femur heads). Plans were created for 6 MV photon beam using RapidArc
      technique in Eclipse treatment planning system. Dose calculations were performed
      with AAA and AXB for same number of monitor units and identical beam setup. Mean
      and maximum doses to planning target volume (PTV) and OARs were analyzed.
      Additionally, minimum dose to PTV and V100 was analyzed. Finally, point-dose
      difference between planar dose distributions of AAA and AXB plans was
      investigated. RESULTS: The highest dose difference was up to 0.43% (range: 0.05
      0.43%, P> 0.05) for PTV and 1.98% (range: 0.22-1.98%, P> 0.05) for OARs with AAA
      predicting higher dose than AXB. The V100 values of AAA plans (95 %) and AXB
      plans (range: 93.1-97.9 %) had an average difference of 0.89 +/- 1.47% with no
      statistical significance (P = 0.25411). The point-dose difference analysis showed
      that AAA predicted higher dose than AXB at significantly higher percentage (in
      average 94.15) of total evaluated points. CONCLUSION: The dosimetric results of
      this study suggest that the AXB can perform the dose computation comparable to
      AAA in RapidArc prostate cancer treatment plans that are generated by a partial
      single-arc technique.

PMID- 24125979
TI  - Histopathological study of adrenocortical carcinoma with special reference to the
      Weiss system and TNM staging and the role of immunohistochemistry to
      differentiate it from renal cell carcinoma.
AB  - BACKGROUND: Adrenocortical carcinomas (ACC) are rare tumors with an incidence of
      1-2/million/year. They account for 0.05-0.2% of all malignancies. AIMS AND
      OBJECTIVES: This study was aimed to evaluate the Weiss system to diagnose ACCs
      and to compare it with TNM staging. The role of immunohistochemistry (IHC) was
      also evaluated to differentiate ACC from other differential diagnoses especially,
      renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 10 ACCs were
      included from April, 2000 to March, 2012. All the relevant information like
      weight, tumor size, gross features was recorded. Multiple sections were taken for
      histologic examination. Immunomarkers like vimentin, synaptophysin, Melan-A,
      calretinin, inhibin, EMA, cytokeratin, and Ki-67 were used. RESULTS: Out of 10
      cases of ACCs (diagnosed by the Weiss system), the tumors were in TNM stage I (1
      case), stage II (2 cases), stage III (5 cases), and stage IV (2 cases). The Weiss
      score in stages I-IV was 4; 5-7; 6-8; and 5-9 respectively. ACCs were positive
      for vimentin, inhibin, Melan-A, calretinin and negative for EMA and cytokeratin.
      Proliferative index (Ki-67/MIB-1) was >= 20 % (20-65%). CONCLUSION: Both the
      Weiss system and TNM staging are useful in predicting the malignant behavior and
      prognosis of ACC. Weight and tumor size, though originally not included in the
      Weiss system, are also important parameters. In lower stages (stages I and II),
      the Weiss score is low (4-7) while the score is high (6-9) when the tumor is in
      higher stages (stages III and IV). IHC plays a vital role to confirm the
      diagnosis and to exclude the possibility of RCC.

PMID- 24125980
TI  - Evaluation of antitumor efficacy and toxicity of novel 6-nitro-2-(3-chloropropyl)
      1H-benz[de]isoquinoline-1,3-dione in vivo in mouse.
AB  - AIM: This study was aimed to assess the in vivo anti-tumoral potency of the novel
      6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione [Compound 1] that
      has earlier demonstrated excellent cytotoxicity in 15 out of 17 human tumor cell
      lines tested. MATERIALS AND METHODS: Two murine tumors namely Sarcoma-180 (S-180)
      and Ehrlich ascites carcinoma (EAC) were used to measure its in vivo anti-tumor
      activity through the increase in median survival times (MST) of drug treated (T)
      over untreated control (C) mice. Drug-induced toxicity in respect of
      hematological parameters, femoral bone marrow and splenic cellularity as well as
      biochemical parameters and histopathology of liver and kidney were assessed in
      vivo in normal and S-180 bearing mice sequentially on days 9, 14 and 19 following
      drug treatment at the optimum dose of 60 mg/kg administered from day 1 to 7.
      RESULTS: Results revealed significant tumor regression effects in S-180 and EAC
      as T/Cmax values of 138 and 189 were obtained at its optimum dose of 60 mg/kg for
      QD1-7 . Toxicity assay indicated no significant cardiotoxicity, hepatotoxicity or
      nephrotoxicity of the compound in normal and S-180 bearing mice. An initial
      hyposplenic cellularity and the femoral bone marrow suppression effect observed
      on day 9 reached normalcy by day 19. HPLC analysis revealed that it has
      appreciable stability (half-life ~ 3 h) in murine blood plasma in vitro.
      CONCLUSION: Above results justify potential candidature of the compound for
      further drug development.

PMID- 24125981
TI  - Acute radiation pneumonitis after conformational radiotherapy for nonsmall cell
      lung cancer: clinical, dosimetric, and associated-treatment risk factors.
AB  - BACKGROUND: Conformational thoracic radiotherapy (CTR) is a key-treatment in
      locally advanced nonsmall cell lung cancer (LA-NSCLC). Acute radiation
      pneumonitis (ARP) is one of the major complications. AIMS: To evaluate the
      predictors of ARP after CTR in the treatment of LA-NSCLC. MATERIALS AND METHODS:
      A total of 47 consecutive patients (pts) were treated with CTR for LA-NSCLC and
      retrospectively analyzed. The mean total dose of radiation therapy (RT) was 65
      Gy, with respiratory gating (RG) in 19 cases. Induction and concomitant
      chemotherapy was performed in 33 pts (70%) and 41 pts (87%), respectively.
      RESULTS: Eleven pts (23%) had an ARP resulting in death for one pt. In univariate
      analysis, age, sex, pretherapeutic value of forced expiratory volume (FEV), not
      gated radiotherapy and type of concomitant chemotherapy did not appear as
      contributing factors in contrast to the administration of induction gemcitabine (
      p = 0.03). The occurrence of ARP was significantly associated with nontumor lung
      volumes irradiated to 13 Gy (V13, p = 0.04), 20 Gy (V20, p = 0.02), and 25 Gy
      (V25, p = 0.006), the mean lung dose ( p = 0.008) and lung normal tissue
      complication probability (NTCP) ( p = 0.004). In multivariate logistic regression
      analysis, the occurrence of ARP was significantly associated with age >75 years
      (odds ratio (OR) = 16.72, confidence interval (CI) 95% 1.77-157.87) and
      administration of induction gemcitabine (OR = 18.08, CI 95% 1.09-300.08).
      CONCLUSION: ARP is a common acute complication, requiring close posttreatment
      follow-up, particularly for elderly patients. The use of gemcitabine before
      radiation should be avoided. The benefits and risks of CTR must be carefully
      analyzed, according to the dosimetric parameters.

PMID- 24125982
TI  - Carotid sparing hypofractionated tomotherapy in early glottic cancers: Refining
      image guided IMRT to improve morbidity.
AB  - OBJECTIVE: Carotid artery damage has been reported secondary to radiotherapy. We
      report the feasibility of implementing hypofractionated laryngeal irradiation
      using carotid sparing tomotherapy (HT) and analyze the image guidance (IG)
      policy. MATERIALS AND METHODS: Five patients with early glottic cancer (EGC) had
      radiotherapy using 3D conformal technique (conf) while repeat treatment plans
      were produced with helical tomotherapy using carotid sparing techniques (cstomo).
      Inverse and forward planned dose volume histograms were analyzed. Three hundred
      and sixty four daily images of 14 patients having daily Megavoltage head and neck
      CT imaging prior to irradiation were analyzed to assess errors. RESULTS: There
      was no significant difference in the maximum and mean dose to the PTV (P = 0.058,
      0.66). The left / right carotid median doses were significantly less in the
      cstomo plans as compared to conf plans (P = 0.0001/ 0.026). Cstomo plans had
      significantly better PTV Conformity Index (CI) (P = 0.0006) with comparable
      Homogeneity Index. A CTV-PTV margin of 5.3, 4, 5.3 cm in the 3 axes were
      calculated using Van Herks formula. After average shifts from imaging for first 5
      fractions (AS5) were applied to remaining fractions, the residual shifts in the
      calculated CTV-PTV margins reduced to 2.9, and 2.1 in the X, Y axes respectively
      allowing further adaptation of PTV margin from fraction 6. CONCLUSIONS: Carotid
      sparing was possible using cstomo plans with significantly better conformity.
      Applying AS5 could enable us to reduce the PTV (3 mm) margin in X, Y axes for the
      remaining 15 fractions.

PMID- 24125983
TI  - A research about breast cancer detection using different neural networks and K
      MICA algorithm.
AB  - Breast cancer is the second leading cause of death for women all over the world.
      The correct diagnosis of breast cancer is one of the major problems in the
      medical field. From the literature it has been found that different pattern
      recognition techniques can help them to improve in this domain. This paper
      presents a novel hybrid intelligent method for detection of breast cancer. The
      proposed method includes two main modules: Clustering module and the classifier
      module. In the clustering module, first the input data will be clustered by a new
      technique. This technique is a suitable combination of the modified imperialist
      competitive algorithm (MICA) and K-means algorithm. Then the Euclidean distance
      of each pattern is computed from the determined clusters. The classifier module
      determines the membership of the patterns using the computed distance. In this
      module, several neural networks, such as the multilayer perceptron, probabilistic
      neural networks and the radial basis function neural networks are investigated.
      Using the experimental study, we choose the best classifier in order to recognize
      the breast cancer. The proposed system is tested on Wisconsin Breast Cancer (WBC)
      database and the simulation results show that the recommended system has high
      accuracy.

PMID- 24125984
TI  - Expression profiling based on graph-clustering approach to determine colon cancer
      pathway.
AB  - CONTEXT: Colorectal cancer is the second leading cause of cancer deaths
      worldwide. DNA microarray-based technologies allow simultaneous analysis of
      expression of thousands of genes. AIM: To search for important molecular markers
      and pathways that hold great promise for further treatment of patients with
      colorectal cancer. MATERIALS AND METHODS: Here, we performed a comprehensive gene
      level assessment of colorectal cancer using 35 colorectal cancer and 24 normal
      samples. RESULTS: It was shown that AURKA, MT1G, and AKAP12 had a high degree of
      response in colorectal cancer. Besides, we further explored the underlying
      molecular mechanism within these different genes. CONCLUSIONS: The results
      indicated calcium signaling pathway and vascular smooth muscle contraction
      pathway were the two significant pathways, giving hope to provide insights into
      the development of novel therapeutic targets and pathways.

PMID- 24125985
TI  - Oral submucous fibrosis: Comparing clinical grading with duration and frequency
      of habit among areca nut and its products chewers.
AB  - AIMS AND OBJECTIVES: To evaluate the effect of frequency, duration and type of
      areca nut products on the incidence and severity of oral submucous fibrosis
      (OSMF). MATERIALS AND METHODS: Patients with the limited mouth opening and
      associated blanched oral mucosa with palpable fibrous bands were included in this
      study. Biopsies were done and the informed consent was taken from each patient
      included in this study. The tissues were taken from the affected areas and then
      studied histopathologically. The data was analysed statistically using X(2)-test.
      RESULTS: In this present prospective study done in 197 subjects (189 males and 8
      females) who were screened and diagnosed clinically having OSMF with age ranging
      from 22 to 61 years with mean 38.8 years. Gutkha-chewing habit alone was
      identified in 58 subjects and those associated with gutkha and tobacco were 33
      with mean age of 28.2 years and 32.3 years, respectively. The number of people
      getting affected with OSMF is more associated with gutkha and areca nut with the
      P-value of the analysis ranging from 0.05 to 0.01. CONCLUSION: The occurrence of
      OSMF is related to areca nut and its products. The duration and frequency of its
      use and type of areca nut product has effect on the incidence and severity of
      OSMF. Gutkha and pan masala have more deleterious and faster effects on oral
      mucosa. The gutkha-chewing habit along with the other habits does not have any
      significant effect on the rate of occurrence and incidence and severity of the
      OSMF.

PMID- 24125986
TI  - Estimation of patient dose in (18)F-FDG and (18)F-FDOPA PET/CT examinations.
AB  - PURPOSE: To estimate specific organ and effective doses to patients resulting
      from the (18)F-FDG ((18)F-2-deoxy-D-glucose) and (18)F-FDOPA (6-fluoro-((18)F)-L
      3, 4-dihydroxyphenylalanine) PET/CT examinations for whole body and brain.
      MATERIALS AND METHODS: Three protocols for whole body and three for brain PET/CT
      were used. The CTDI values were measured using standard head and body CT phantoms
      and also computed using a software CT-Expo for dose evaluation from the CT
      component. OLINDA software based on MIRD method was used for estimating doses
      from the PET component of the PET/CT examination. RESULTS: The organ doses from
      (18)F-FDG and (18)F-FDOPA whole body and brain PET/CT studies were estimated. The
      total effective dose from a typical protocol of whole body PET/CT examination was
      14.4 mSv for females and 11.8 mSv for male patients from (18)F-FDG, whereas it
      was 11 mSv for female and 9.1 mSv for male patients from (18)F-FDOPA. The total
      effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv
      for females and 5.1 mSv for males from (18)F-FDG whereas it was 3.7 mSv for
      females and 2.8 mSv for males from (18)F-FDOPA. CONCLUSIONS: The effective
      radiation doses from whole body PET/CT examination was approximately 4-8 times
      higher than the background radiation dose from both (18)F-FDG and (18)F-FDOPA
      scans, while it was 1-3 times the background radiation dose from PET/CT scans of
      brain.

PMID- 24125987
TI  - Chronic myeloid leukemia with pregnancy: Successful management of pregnancy and
      delivery with hydroxyurea and imatinib continued till delivery.
AB  - The concomitant occurrence of pregnancy and chronic myeloid leukemia is uncommon.
      We describe the successful management of a 30-year-old G3 P0, A2 woman who was
      diagnosed to have chronic myelogenous leukemia (CML) in the third trimester of
      her pregnancy with intra-uterine growth retardation and oligohydroamnios. She was
      started on hydroxyurea and imatinib, and was continued till delivery and beyond.
      The use of imatinib did not have any adverse effects on the fetus, except for low
      birth weight and low APGAR at birth, but the later progress of the child was
      normal. We conclude that imatinib and hydroxyurea can be continued even at the
      third trimester in a pregnant lady with CML, if necessary.

PMID- 24125988
TI  - Primary bone lymphoma with multiple vertebral involvement.
AB  - A 20-year-old student presented with 2 months history of fever and night sweats,
      15 days history of low backache, progressive weakness of both limbs of 7 days
      duration, and urinary retention for last 24 h. Examination revealed a sensory
      level at D 10 dermatome and grade two power in both the lower limbs with absent
      reflexes. Examination of spine revealed a knuckle at T8 level, which was tender
      on palpation. MRI spine showed erosion of D11-12 and L1 in vertebral bodies with
      destruction of left pedicles, transverse processes and lamina, and a prominent
      psoas abscess. Post gadolinium study revealed ring-enhancing lesions in the D11
      12 and L1 vertebrae as well as the dural sac. Fine needle aspiration cytology
      (FNAC) and bone biopsy demonstrated a non-Hodgkin's lymphoma (NHL, large cell
      high-grade) of the spine (primary), which as per age is the youngest case of NHL
      ever reported in literature with multiple vertebral involvement.

PMID- 24125989
TI  - Imaging of dedifferentiated papillary thyroid carcinoma with left ventricular
      metastasis: A rare presentation of papillary thyroid metastatic disease.
AB  - Cardiac metastasis in thyroid cancer is extremely rare. Iodine-131-d whole-body
      scan has been used widely to detect thyroid metastasis. However, in
      dedifferentiated cases, iodine scan has low diagnostic value particularly for
      diagnosing cardiac metastasis. In the absence of (131)I uptake, (18)F-fluoro-2
      deoxyglucose positron emission tomography ((18)F-FDG PET) can be used as an
      alternative and has a high sensitivity for thyroid metastasis, but still low
      sensitivity for cardiac metastasis. Therefore, meticulous attention to the
      pattern of uptake and comparison with patients' previous studies is critical.
      Additionally, cardiac magnetic resonance imaging (MRI) can provide additional and
      critical information.

PMID- 24125990
TI  - Molecular diagnosis of lymphoblastic leukemia.
AB  - The mixed lineage leukemia (MLL) gene at chromosome band 11q23 is commonly
      involved in reciprocal translocations that is detected in acute leukemia. The MLL
      gene, commonly known as mixed lineage leukemia or myeloid lymphoid leukemia, has
      been independently identified and cloned from the 11q23 breakpoint of acute
      leukemia. We describe a patient with acute lymphoblastic leukemia whose cells had
      shown reciprocal translocation between short arm (p21) of chromosome 2 and long
      arm (q23) of chromosome number 11 [t(2;11) (p21;q23)] by cytogenetic analysis.
      Fluorescence in situ hybridization analysis (FISH) was also performed for
      reconfirmation with a probe for MLL which showed split signals, hybridizing to
      both the derivative 2 and 11 chromosomes. Our study confirmed FISH as the most
      suitable assay for detecting MLL rearrangements because of its sensitivity and
      speed. It recommended that FISH should be used as complementary to conventional
      cytogenetic analysis. In conclusion, evaluation of the t(2;11)(p21;q23) was done
      by molecular clarification and flow cytometry.

PMID- 24125991
TI  - Multifocal thoracic chordoma mimicking a paraganglioma.
AB  - Chordoma of thoracic vertebras is a very rare locally invasive neoplasm with low
      grade malignancy arising from embryonic notochordal remnants. Radical surgery
      remains the cornerstone of the treatment. We describe a case of multifocal T1-T2
      chordoma, without bone and disc involvement, incidentally misdiagnosed as a
      paraganglioma, occurring in a 47-year-old male asymptomatic patient. Neoplasm was
      radically removed by an endocrine surgeon through a right extended cervicotomy. A
      preoperative reliable diagnosis of chordoma, as in the reported case, is often
      difficult. Radical surgery can provide a favorable outcome but, given the high
      rates of local recurrence of this neoplasm, a strict and careful follow-up is
      recommended. Although very rare, chordoma should be suggested in the differential
      diagnosis of the paravertebral cervical masses of unknown origin. Spine surgeon
      consultation and a FNB should be routinely included in the multidisciplinary
      preoperative work-up of these neoplasms.

PMID- 24125992
TI  - Bleomycin induced flagellate erythema: Revisiting a unique complication.
AB  - Bleomycin induced flagellate dermatitis is a rare and unique adverse effect. With
      the declining use of bleomycin, this complication is becoming increasingly
      infrequent in common clinical practice. We herein describe a case of a 22-year
      old Indian male with Hodgkin's lymphoma, Ann Arbor stage IIBEX developing
      flagellate dermatitis following 1(st) cycle of chemotherapy with ABVD regimen.
      The diagnostic dilemma in the illustrative case underscores the importance of
      awareness and prompt identification and treatment of this dermatological toxicity
      in limiting morbidity in patients undergoing bleomycin based combination
      chemotherapy. In patients having severe rash, bleomycin should be expeditiously
      discontinued. Omission of bleomycin does not compromise the treatment outcome in
      the majority of patients with Hodgkin's lymphoma.

PMID- 24125994
TI  - Solid pseudo-papillary tumor of pancreas: A rare case report and review of Indian
      literature.
AB  - Solid pseudo-papillary tumor (SPT) of the pancreas is a rare pancreatic tumor,
      well known for its predilection for young women. As the tumor has favorable
      prognosis, differentiating it from other pancreatic tumors with aggressive
      behavior is necessary. We present a rare case of SPT and review the literature
      about SPT cases published from India.

PMID- 24125993
TI  - Carcinoma lung presenting with choroidal metastasis as initial presentation: a
      rarity.
AB  - Diminished vision due to choroidal metastasis as the primary symptom of lung
      cancer is very uncommon. Here, we report such a presentation in a 54-year-old
      male patient of small cell lung cancer. The outcome is usually dismal with this
      kind of presentation. The patient received systemic chemotherapy as well as
      intravitreal bevacizumab but with no improvement in vision. The patient had been
      given external beam radiotherapy and showed subjective improvement in his ocular
      symptoms.

PMID- 24125995
TI  - Sacral pain as the initial symptom in primary Hodgkin's lymphoma of bone.
AB  - Progressive painless enlargement of peripheral lymph nodes is the most common
      presentation of Hodgkin's lymphoma. The bone involvement is seen particularly in
      the later stages, but very rarely in early stages of the disease. Primary osseous
      Hodgkin lymphoma is exceedingly rare. Here, we report a case of Primary osseous
      Hodgkin lymphoma in a 35-year-old male presenting with osteolytic lesions of
      iliac and sacral bone without other symptoms. Histopathology examination revealed
      Hodgkin's disease. All other investigations (including computed tomography of the
      chest, abdomen and pelvis, bone marrow aspiration) were negative for occult
      disease. Polychemotherapy was started and the symptoms resolved. The case report
      highlights the importance of clinical suspicion of primary Hodgkin lymphoma of
      the bone, especially those involving the pelvis bones.

PMID- 24125996
TI  - Rare case of primary mucinous adenocarcinoma of vagina.
AB  - Here we present a rare case of primary mucinous adenocarcinoma of vagina treated
      successfully with wide local excision and post-operative radiotherapy. There was
      no recurrence even after four years.

PMID- 24125997
TI  - Primary pleural synovial sarcoma: A rare cause of hemorrhagic pleural effusion in
      a young adult.
AB  - This is a case report of a young adult presenting with hemorrhagic pleural
      effusion. Chest CT scan showed loculated pleural effusion with pleural nodule.
      Whole body PET scan showed thickening of pleura with multiple enhancing pleural
      nodules with different metabolic activity. Pleural nodule was biopsied which on
      histopathology showed pleural synovial sarcoma.

PMID- 24125998
TI  - 18F-FDG-PET/CT in a patient with suspected recurrence of germ cell tumor.
AB  - At present, the available clinical practice guidelines for the management of
      patients with germ cell tumor (GCT) assign to Positron Emission Tomography (PET)
      scan a role in the evaluation of the residual mass at the end of the treatment of
      advanced seminoma, while a possible role of this tool in the strategy of follow
      up has not been defined yet. We are presenting a case of a patient treated for a
      GCT with an increase of the marker levels during the follow-up where a PET/CT
      with 18F-FDG was the only noninvasive examination able to correctly identify the
      site of disease recurrence. This case shows how this tool could have a role, in
      addition to morphological examinations, in the management of patients with GCT
      during the follow-up.

PMID- 24125999
TI  - Bilateral adenomyoepithelioma of breast.
AB  - Adenomyoepithelioma is a rare tumor characterized by proliferation of two
      different cell populations. These tumors have a variable biological behavior.
      Majority of them are benign but have a tendency to recur locally. Malignant
      transformation is rare in this disease and distant metastasis is rarer still. We
      report here an unusual case of bilateral adenomyoepithelioma at an unusual age
      and showing a remarkable response to an unconventional drug, tyrosine kinase
      inhibitor "imatinib".

PMID- 24126000
TI  - Hodgkin's lymphoma of the breast.
AB  - Hodgkin's lymphoma of the breast is very rare. We report a case of Hodgkin's
      lymphoma of the breast in a 61 year old post-menopausal female who presented with
      a 3 month history of left breast painless lump. Excision biopsy was done and
      histology showed nodular sclerotic Hodgkin's lymphoma confirmed by
      immunohistochemical staining.

PMID- 24126001
TI  - Osteoid differentiation in mesodermal (mullerian) adenosarcoma of ovary.
AB  - A 55-year-old female presented with abdominal pain and 10 cm mass per abdominal
      examination. Computerized tomography scan of abdomen and pelvis revealed a
      heterogeneously enhancing solid cystic mass right ovarian mass and mild ascites.
      Surgery was performed. Specimens were sent for examination. Microscopic
      examination revealed an admixture of benign but occasionally atypical appearing
      mullerian type glands with sarcomatous stroma. Solid area showed undifferentiated
      tumour cells. Atypical mitoses and necrosis were also seen. Areas with extensive
      benign osteoid surrounded by fibroblastic stroma were also present. Glandular
      component showed positivity for CK-7, AE-1 and EMA while sarcomatous areas showed
      positivity for vimentin only. Mullerian adenosarcoma of ovary with sarcomatous
      overgrowth (SO) having heterologous component was confirmed. Postoperative 3
      cycles of chemotherapy was given and the patient was well till date (three months
      after surgery).

PMID- 24126002
TI  - Co-occurrence of diffuse large B cell non-hodgkin lymphoma and chronic hepatitis
      C in Algerian patients: two case reports.
AB  - For the first time in Algeria, we report on the presentation, diagnosis and
      management of two cases of diffuse large B cell NHL with chronic HCV infection.
      Both Algerian patients came for medical consult without HCV-related symptoms.
      Systematic serological tests to identify HIV and hepatitis B and C infections
      which performed on all patients led to HCV diagnosis. Chemotherapy was given to
      both patients without exacerbation of the HCV infection. These observed cases
      shed new light on the possible pathogenesis of NHL in Algerian population.
      Indeed, in Algeria, HCV may partly been responsible of the unexplained increase
      of NHL incidence in Eastern region of Algeria especially among those who are
      frequently exposed to HCV risk factors (haemodialysis and dental care).
      Furthermore, our observations underscore the importance of prevention programmes
      including screening to control HCV in Algeria.

PMID- 24126003
TI  - Isolated cerebral post-transplant lymphoproliferative disorder in a lymphoma
      recipient.
AB  - Post-transplant lymphoproliferative disorder (PTLD) can occur after solid organ
      transplantation (SOT) or hematopoietic stem cell transplantation (HSCT). The
      majority of PTLDs are related to the reactivation of Epstein-Barr virus (EBV) in
      the lymphoid organs. PLTDs in HSCT recipients tend to present with systemic
      involvement, and isolated PTLD in these patients is rare. Only 14 isolated
      cerebral PTLDs have been reported in HSCT recipients, and none have been reported
      in lymphoma patients. When diagnosing PTLD in a lymphoma patient, it is
      challenging to discriminate between a PTLD that originated from previous disease
      and a newly developed clone and to distinguish between donor and recipient
      origin. In this report, we present the first case of a B-cell lymphoma patient
      who developed isolated PTLD in the CNS, and we confirmed that the PTLD originated
      in a distinct clone and from a different origin. Furthermore, the role of EBV-DNA
      monitoring in such patients is discussed.

PMID- 24126004
TI  - Solid pseudopapillary tumor of pancreas with sickle cell trait: a rare case
      report.
AB  - Solid pseudopapillary tumor of pancreas is a rare pancreatic neoplasm affecting
      young women, has low malignant potential and amenable for surgical excision with
      good long-term survival. Sickle cell trait is benign condition, which involves
      one normal beta-globin chain and one HbS chain. Although it is a benign
      condition, individuals are prone to have rare complications that may predispose
      to death under certain circumstances. We report a rare coexistence of solid
      pseudopapillary tumor of pancreas with sickle cell trait in an 18-year-old female
      who underwent distal pancreatectomy with splenectomy. Histopathological
      examination and haemoglobin electrophoresis confirmed the diagnosis.

PMID- 24126005
TI  - Verruco-papillary lesions in relation to human papilloma virus.
AB  - Plethora of pathologic conditions may affect the normal morphologic
      characteristics and intactness of the oral mucosa, presenting as surface
      alterations.The prevalence of the different types of HPV worldwide has
      implications for the effectiveness of HPV vaccinations against HPV-induced
      carcinogenesis. This article discusses HPV related lesions with emphasis on
      verrucopapillary lesions.

PMID- 24126006
TI  - Recurrence of keratocyst in nevoid basal cell carcinoma syndrome: A major
      diagnostic dilemma for clinicians.
AB  - The odontogenic keratocysts (OKC) usually represent a particular entity that has
      been of interest primarily due to biological aggressiveness and to its frequent
      recurrence. Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin
      syndrome is a hereditary condition characterized by a wide-range of developmental
      abnormalities and a predisposition to neoplasms. There are several possible
      reasons why OKC recur so frequently and require meticulous surgical planning and
      execution. This article has attempted to show that there is a lack of published
      evidence regarding the cause of frequent recurrent of OKC that presented in
      NBCCS. However, the findings of the study revealed differences in opinion
      regarding the treatment modalities, which necessitates further long term clinical
      studies that could precisely document certain reliable guidelines in this point
      of view.

PMID- 24126007
TI  - Plant products for radioprotection: Boon or bane?

PMID- 24126008
TI  - Quorum sensing inhibitors: how strong is the evidence?
AB  - Because of its promising effect as an alternative to antibiotics, quorum sensing
      disruption is an intensively studied field, and there are many studies that
      describe the quorum sensing inhibitory activity of natural and synthetic
      compounds. In this opinion article, we present an overview of recent literature
      with respect to quorum sensing inhibitors. Most of this research is based on
      experiments with quorum sensing signal molecule reporter strains. However, these
      experiments are prone to bias due to other effects compounds may have on reporter
      strains. We argue that researchers should perform adequate control experiments
      and should carefully assess toxicity of the compounds in the bacterial species
      they are working with in order to confirm that what they observe really is quorum
      sensing inhibition. 

PMID- 24126009
TI  - Localized flushing absence after abobotulinum toxin A cosmetic treatment.

PMID- 24126010
TI  - The growth of very-low-birth-weight infants at 5 years old in Taiwan.
AB  - BACKGROUND: The goal of this study was to compare the growth and effect of growth
      on cognitive performance at 5 years of age of a group of very-low-birth-weight
      (VLBW) infants and a group of healthy full-term infants. METHODS: Beginning in
      1995, under the sponsorship of the Premature Baby Foundation, the Society of
      Neonatology, Taiwan, conducted a multicenter follow-up study of VLBW infants in
      Taiwan. The study enrolled 322 VLBW infants and 103 controls for assessment of
      growth data and cognitive performance at several time points from birth through
      to 5 years of age. Growth data were assessed with measurements of weight, height,
      and head circumference taken at the ages of 6 months, 12 months, 24 months, and
      60 months. Cognitive performance was assessed at the age of 5 years. The VLBW
      infants were regarded as "failed" if a measurement was 2 standard deviations
      below the mean measurement of the control group. Neonatal and perinatal data had
      been collected prospectively as part of a longitudinal study. Cognitive
      performance was assessed using the Chinese version of the Wechsler Preschool and
      Primary Scale of Intelligence (WPPSI-R). RESULTS: From 6 months to 5 years, VLBW
      infants had lower weight, height, and head circumference than the controls. Two
      hundred twenty-four VLBW infants (69.6%) returned for assessment at 5 years old.
      Of the 224 VLBW infants, complete sets of measurements of weight, height, and
      head circumference were obtained for 126 cases (56.3%), 127 cases (56.7%), and
      106 cases (47.3%), respectively. Of these, 13 patients (10.3%) failed in weight,
      11 patients (8.7%) failed in height, and 17 patients (16.0%) failed in head
      circumference at the age of 5 years. The mean WPPSI-R scores at the age of 5
      years for VLBW children were: 94.1 +/- 16.4 (performance IQ), 87.2 +/- 12.8
      (verbal IQ), and 89.5 +/- 14.6 (full IQ). All of these values were also lower
      than those of the control group, with the differences being statistically
      significant (p < 0.05). The WPPSI-R scores of VLBW children who failed in head
      circumference were notably lower than those of VLBW children whose head
      circumference had caught up with that of their peers. CONCLUSION: The growth of
      VLBW infants was lower than that of healthy full-term infants through 5 years of
      age. The cognitive performance for VLBW children was also decreased compared to
      that of the control group, and there was an association between slower growth and
      decreased cognitive ability.

PMID- 24126011
TI  - Efficacy of FiO2 increase during the initial resuscitation of premature infants <
      29 weeks: an observational study.
AB  - OBJECTIVE: To evaluate the heart rate (HR) and oxygen saturation (SpO2) at 15
      second intervals within 60 seconds after incremental increases of fractional
      inspired oxygen (FiO2) during resuscitation of infants younger than 29 weeks
      requiring two different forms of ventilatory support. STUDY DESIGN: Retrospective
      observational study. METHODS: Forty-three infants were stabilized, 14 by
      continuous positive airway pressure exclusively (CPAP group), and 29 by positive
      pressure ventilation (PPV group). Both groups received ventilatory support in a
      special bed with two cameras enabling the evaluation of all interventions
      including HR, SpO2, FiO2, positive inflation pressure, and positive end
      expiratory pressure values. FiO2 was commenced at 0.30 and titrated in 0.1-0.2
      increments every 30-60 seconds. The relationships between the incremental
      increases of FiO2 and related SpO2 and HR changes were evaluated. RESULTS:
      Although there was an inverse correlation between initial FiO2 and SpO2 in both
      groups, a significant positive correlation between the incremental increase of
      FiO2 and SpO2 changes after 30 seconds was found only in the CPAP group. Only
      higher initial levels of FiO2 had a positive effect on the improvement in SpO2 in
      the PPV group. CONCLUSION: The efficacy of FiO2 titration in 0.1-0.2 increments
      may be attenuated and delayed in extremely preterm infants required PPV during
      the first 6 minutes of life.

PMID- 24126012
TI  - Mechanistic study on the biological effects of silver and gold nanoparticles in
      Caco-2 cells--induction of the Nrf2/HO-1 pathway by high concentrations of silver
      nanoparticles.
AB  - The most commonly used metal nanoparticles (NPs) across diverse applications,
      including in agro-food applications, include silver (AgNPs) and gold (AuNPs). In
      the present study, we aimed to investigate the biological responses and possible
      toxicological effects of AgNPs and AuNPs in the Caco-2 cells as an in vitro human
      GI tract model. Both AgNPs and AuNPs were internalized into the cytoplasm of Caco
      2 cells, but not within the nucleus and only exposure to high concentrations of
      AgNPs, but not AuNPs, caused acute cytotoxicity and depolarization of the
      mitochondrial membrane potential. In addition, only AgNPs significantly depleted
      the total intracellular glutathione level, induced the activation of the stress
      responsive gene, Nrf2, and dramatically increased the expression of heme
      oxygenase-1 (HO-1). Furthermore, siRNA silencing of Nrf2 transcripts
      significantly reduced the AgNP-induced HO-1 mRNA induction, suggesting a key role
      for Nrf2 in the control of HO-1 expression. Taken together, AgNPs but not AuNPs
      induced acute cytotoxicity and cellular responses via the oxidative stress
      related activation of Nrf2/HO-1 signaling pathway in Caco-2 cells. The expression
      of HO-1 transcripts may be useful as a sensitive marker for safety evaluation of
      AgNPs in the GI tract of humans. 

PMID- 24126013
TI  - Pre-exposure prophylaxis against rabies in children: safety of purified chick
      embryo cell rabies vaccine (Vaxirab N) when administered by intradermal route.
AB  - WHO recommends that children living in highly endemic regions be considered for
      pre-exposure prophylaxis with rabies vaccine, since they will be at continual,
      frequent or increased risk of exposure to the animal bites. The recommendations
      will come from WHO only after it has been proven by many previous scientific
      studies among children which have shown that pre-exposure prophylaxis using
      Purified Chick Embryo Cell Vaccine (PCECV) is safe and well tolerated. This has
      been mentioned in the discussion. The authors have not claimed/nor assumed in any
      part of their manuscript that they are the first to demonstrate the safety of
      purified chick embryo cell rabies vaccine when administered by intradermal route
      for pre-exposure prophylaxis against rabies in children.

PMID- 24126014
TI  - Evaluation of health care workers' knowledge and functioning of blood centres in
      north India: a questionnaire based survey.
AB  - For quality, safety and efficacy of blood components, adequate infrastructure and
      trained manpower are essential requirements. Objective of this study is to
      analyse existing systems of transfusion services in north India, various testing
      methodologies practiced and to assess the level of knowledge of health care
      professionals working at these centres. Participants included laboratory
      technicians and nurses whose knowledge and various practices at blood centres
      were assessed using a questionnaire. Knowledge of those having more experience,
      working at urban blood centres and received an additional training was
      significantly higher. Only a few blood centres are performing all mandatory tests
      on donors' samples. 

PMID- 24126015
TI  - Comparative in vitro and in vivo assessment of toxin neutralization by anti
      tetanus toxin monoclonal antibodies.
AB  - Tetanus is caused by the tetanus neurotoxin (TeNT), a 150 kDa single polypeptide
      molecule which is cleaved into an active two-chain molecule composed of a 50 kDa
      N-terminal light (L) and a 100 kDa C-terminal heavy (H) chains. Recently,
      extensive effort has focused on characterization of TeNT binding receptors and
      toxin neutralization by monoclonal antibodies (mAbs). Toxin binding inhibition
      and neutralization is routinely assessed either in vitro by the ganglioside GT1b
      binding inhibition assay or in vivo using an animal model. These two assay
      systems have never been compared. In the present study, we report
      characterization of eleven mAbs against different parts of TeNT. The toxin
      inhibitory and neutralization activity of the mAbs was assessed in vitro and in
      vivo respectively. Our data demonstrated that seven mAbs bind to fragment C of
      the heavy chain, two mAbs react with the light chain, one mAb recognizes both
      chains and one mAb reacts with neither light chain nor fragment C. Six fragment C
      specific mAbs were able to inhibit TeNT binding to GT1b ganglioside in vitro but
      three failed to neutralize the toxin in vivo. One in vitro inhibitory mAb (1F3E3)
      was found to synergize with the in vivo neutralizing mAbs to reduce toxin lethal
      activity in vivo. Sequencing of the immunoglobulin heavy and light chain variable
      region genes revealed that the three in vivo neutralizing mAbs were derived from
      a common origin. Altogether, our data suggests that fragment C specific mAbs
      contribute to toxin neutralization in both systems, though some of the GT1b
      binding inhibitory mAbs may not be able to neutralize TeNT in vivo. 

PMID- 24126016
TI  - Capacity of HSYA to inhibit nitrotyrosine formation induced by focal ischemic
      brain injury.
AB  - Peroxynitrite-mediated protein tyrosine nitration represents a crucial pathogenic
      mechanism of stroke. Hydroxysafflor yellow A (HSYA) is the most important active
      component of the safflower plant. Here we assess the neuroprotective efficacy of
      HSYA and investigate the mechanism through anti-nitrative pathway. Rats were
      subjected to 60-min ischemia followed by reperfusion. HSYA (2.5-10mg/kg) was
      injected at 1h after ischemia onset. Other groups received HSYA (10mg/kg)
      treatment at 3-9h after onset. Infarct volume, brain edema, and neurological
      score were evaluated at 24h after ischemia. Nitrotyrosine and inducible NO
      synthase (iNOS) expression, as well as NO level (nitrate/nitrite) in ischemic
      cortex was examined within 24h after ischemia. The ability of HSYA to scavenge
      peroxynitrite was evaluated in vitro. Infarct volume was significantly decreased
      by HSYA (P<0.05), with a therapeutic window of 3h after ischemia at dose of
      10mg/kg. HSYA treatment also reduced brain edema and improved neurological score
      (P<0.05). Nitrotyrosine formation was dose- and time-dependently inhibited by
      HSYA. The time window of HSYA in decreasing protein tyrosine nitration paralleled
      its action in infarct volume. HSYA also greatly reduced iNOS expression and NO
      content at 24h after ischemia, suggesting prevention of peroxynitrite generation
      from iNOS. In vitro, HSYA blocked authentic peroxynitrite-induced tyrosine
      nitration in bovine serum albumin and primary cortical neurons. Collectively, our
      results indicated that post-ischemic HSYA treatment attenuates brain ischemic
      injury which is at least partially due to reducing nitrotyrosine formation,
      possibly by the combined mechanism of its peroxynitrite scavenging ability and
      its reduction in iNOS production. 

PMID- 24126017
TI  - Enzymatic generation of the NO/HNO-releasing IPA/NO anion at controlled rates in
      physiological media using beta-galactosidase.
AB  - We introduce a strategy for generating mixtures of nitric oxide (NO) and nitroxyl
      (HNO) at tunable rates in physiological media. The approach involves converting a
      spontaneously HNO/NO-generating ion to a caged (prodrug) form that is essentially
      stable in neutral media, but that can be activated for HNO/NO release by adding
      an enzyme capable of efficiently opening the cage to regenerate the ion. By
      judiciously choosing the enzyme, substrate, and reaction conditions, unwanted
      scavenging of the HNO and NO by the protein can be minimised and the catalytic
      efficiency of the enzyme can be maintained. We illustrate this approach with a
      proof-of-concept study wherein the prodrug is Gal-IPA/NO, a diazeniumdiolate of
      structure iPrHN-N(O)NOR, with R=beta-d-galactosyl. Escherichia coli-derived beta
      d-galactosidase at concentrations of 1.9-15nM hydrolysed 56MUM substrate with
      half-lives of 140-19min, respectively, producing the IPA/NO anion (iPrHN-N(O)NO(
      ), half-life ~3min), which in turn spontaneously hydrolysed to mixtures of HNO
      with NO. Using saturating substrate concentrations furnished IPA/NO generation
      rates that were directly proportional to enzyme concentration. Consistent with
      these data, the enzyme/substrate combination applied to ventricular myocytes
      isolated from wild-type mouse hearts resulted not only in a significant positive
      inotropic effect, but also rescued the cells from the negative inotropy,
      hypercontractions, and occasional cell death seen with the enzyme alone. This
      mechanism represents an alternate approach for achieving controlled fluxes of
      NO/HNO to investigate their biological actions. 

PMID- 24126018
TI  - In vitro organic nitrate bioactivation to nitric oxide by recombinant aldehyde
      dehydrogenase 3A1.
AB  - Organic nitrates (ORNs) are commonly used anti-ischemic and anti-anginal agents,
      which serve as an exogenous source of the potent vasodilator nitric oxide (NO).
      Recently, both mitochondrial aldehyde dehydrogenase-2 (ALDH2) and cytosolic
      aldehyde dehydrogenase-1a1 (ALDH1A1) have been shown to exhibit the ability to
      selectively bioactivate various ORNs in vitro. The objective of the present
      research was to examine the potential role of ALDH3A1, another major cytosolic
      isoform of ALDH, in the in vitro bioactivation of various ORNs, and to estimate
      the enzyme kinetic parameters toward ORNs through mechanistic modeling. The
      extent of bioactivation was assayed by exposing recombinant ALDH3A1 to various
      concentrations of ORNs, and measuring the concentration-time profiles of released
      NO via a NO-specific electrode. Metabolite formation kinetics was monitored for
      nitroglycerin (NTG) using LC/MS/MS. Our results showed that ALDH3A1 mRNA and
      protein were highly expressed in C57BL/6 mouse aortic, cardiac, and hepatic
      tissues, and it was able to release NO from several ORNs, including NTG,
      isosorbide dinitrate (ISDN), isosorbide-2-mononitrate (IS-2-MN), and nicorandil
      with similar Vmax (0.175-0.503nmol/min/mg of ALDH3A1), and Km values of 4.01,
      46.5, 818 and 5.75*10(3)MUM, respectively. However, activation of isosorbide-5
      mononitrate (IS-5-MN) by ALDH3A1 was undetectable in vitro. ALDH3A1 was also
      shown to denitrate NTG, producing primarily glyceryl 1,2-dinitrate (1,2-GDN) in
      preference to glyceryl 1,3-dinitrate (1,3-GDN). Therefore, ALDH3A1 may contribute
      to the bioactivation of ORNs in vivo. 

PMID- 24126019
TI  - General and specific replication profiles are detected in normal human cells by
      genome-wide and single-locus molecular combing.
AB  - Mammalian genomes are replicated under a flexible program, with random use of
      origins and variable fork rates, and many details of the process must be still
      unraveled. Molecular combing provides a set of direct data regarding the
      replication profile of eukaryotic cells: fork rates; organization of the
      replication clusters; proportion of unidirectional forks; and fork dynamics. In
      this study the replication profiles of different primary and immortalized non
      cancer human cells (lymphocytes, lymphoblastoid cells, fibroblasts) were
      evaluated at the whole-genome level or within reference genomic regions harboring
      coding genes. It emerged that these different cell types are characterized by
      specific replication profiles. In primary fibroblasts, a remarkable fraction of
      the mammalian genome was found to be replicated by unidirectional forks, and
      interestingly, the proportion of unidirectional forks further increased in the
      replicating genome along the population divisions. A second difference concerned
      in the proportion of paused replication forks, again more frequent in primary
      fibroblasts than in PBL/lymphoblastoid cells. We concluded that these patterns,
      whose relevance could escape when genomic methods are applied, represent normal
      replication features. In single-locus analyses, unidirectional and paused
      replication forks were highly represented in all genomic regions considered with
      respect to the average estimates referring to the whole-genome. In addition, fork
      rates were significantly lower than whole-genome estimates. Instead, when
      considering the specificities of each genomic region investigated (early to late
      replication, normal or fragile site) no further differentiating features of
      replication profiles were detected. These data, representing the integration of
      genome-wide and single-locus analyses, highlight a large heterogeneity of
      replication profiles among cell types and within the genome, which should be
      considered for the correct use of replication datasets. 

PMID- 24126020
TI  - Subthalamic nucleus deep brain stimulation after bilateral pallidotomy in the
      treatment of generalized dystonia.

PMID- 24126021
TI  - Continuous in-home monitoring of essential tremor.
AB  - BACKGROUND: Essential tremor (ET) is typically measured in the clinic with
      subjective tremor rating scales which require the presence of a clinician for
      scoring and are not appropriate for measuring severity throughout the day. Motion
      sensors can accurately rate tremor severity during a set of predefined tasks in a
      laboratory. METHODS: We evaluated the ability of motion sensors to quantify
      tremor during unconstrained activities at home. 20 ET subjects wore a wireless
      sensor continuously for up to 10 h daily on two days and completed hourly
      standardized tremor assessments involving pre-defined tasks. Mathematical models
      were used to predict tremor rating scores from the sensor data. RESULTS: At home
      tremor scores from hourly standardized assessments correlated with at home tremor
      scores estimated during unconstrained activities immediately following the
      standardized assessments. The hourly standardized assessments did not
      significantly fluctuate throughout the day, while fluctuations in the continuous
      assessments tended to follow changes in voluntary activity level. Both types of
      tremor ratings (standardized and continuous) showed high day-to-day test-retest
      reliability with intraclass correlation coefficients ranging from 0.67 to 0.90
      for continuous ratings and 0.77 to 0.95 for standardized ratings. CONCLUSIONS:
      Results demonstrate the feasibility of continuous monitoring of tremor severity
      at home, which should provide clinicians with a measure of the temporal pattern
      of tremor in the context of daily life and serve as a useful tool for the
      evaluation of novel anti-tremor medications in clinical trials.

PMID- 24126022
TI  - The impact of age and disease duration on the long term outcome of
      neurostimulation of the subthalamic nucleus.
AB  - BACKGROUND: Selection of patients with Parkinson's disease for neurostimulation
      of subthalamic nucleus (STN-DBS) is still poorly studied. AIM: To identify the
      impact of age and disease duration on the outcome of bilateral STN-DBS. METHODS:
      110 operated patients in a single center covering a large range of age and
      disease duration were retrospectively included and followed for up-to 5 years.
      Standardized UPDRS assessments were obtained at 0.5-1 and 3-5 years. Patients
      were stratified into three age groups (<= 55, 56-64 and >= 65 years) and the
      middle age group was further stratified into 2 disease duration subgroups (<15
      years, >= 15 years). RESULTS: The age groups had comparable baseline data except
      for the predefined differences. Compared to baseline early and late intra-group
      "Med Off-Stim On" motor scores were significantly improved for all groups (p <
      0.001). Mood/cognition were significantly improved in younger two groups (p =
      0.008, 0.019) at 0.5-1 year. Inter-group comparisons showed significantly worse
      early and late axial scores for older patients (p < 0.05). All groups had
      comparable postoperative improvement except for the older group which had
      significantly less improvement of early UPDRS-II, late UPDRS-I, and early and
      late PIGD/axial scores. Different disease durations had no effect on the outcome
      except for worse Schwab and England Off-score in longer duration group (p =
      0.02). Side effects of surgery and long-term management were similar. CONCLUSION:
      STN-DBS is an efficient treatment of advanced PD for all treated age-groups.
      Provided strict inclusion criteria are respected, older age and longer disease
      duration are associated with slightly worse effects mainly on L-dopa-resistant
      symptoms.

PMID- 24126023
TI  - Transcallosal diffusion tensor abnormalities in predominant gait disorder
      parkinsonism.
AB  - BACKGROUND: There have been no previous diffusion tensor imaging (DTI) studies
      comparing Parkinson's disease (PD) with postural instability and gait disorder
      (PIGD) parkinsonism. OBJECTIVE: Utilizing DTI with 2-region tractography, we
      conducted a case control study to determine if different brain regions
      representing the neural network of the motor system are differentially affected
      in PIGD compared to PD and controls. METHODS: On a 3 T MR machine, using manual
      ROI (regions of interest) we determined the fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) values on DTI in anatomical brain regions
      representing the extrapyramidal, pyramidal, and transcallosal tracts, aided by 2
      region tractography. FA and ADC were correlated with the Tinetti score (measure
      of gait and balance). RESULTS: Sixty-five subjects (21 PD, 25 PIGD, 19 controls)
      were included in the analysis. We demonstrated greater ADC abnormalities in the
      extrapyramidal, pyramidal and transcallosal motor systems in PIGD compared to
      controls. Multivariate analysis taking into consideration various clinical
      variables showed that the FA (p = 0.02) and ADC (p = 0.001) values in the corpus
      callosum body differentiated PIGD from PD. PIGD with low Tinetti score had a
      lower FA (p = 0.02) and a higher ADC value (corpus callosum body) (p = 0.03)
      compared to those with a high score. CONCLUSIONS: We demonstrated for the first
      time that DTI abnormalities along the transcallosal motor tract in the body of
      the corpus callosum, but not the substantia nigra, differentiated PIGD from PD,
      and the degree of corpus callosum body abnormality correlated with the Tinetti
      score (a measure of risk of falls).

PMID- 24126024
TI  - Acute urinary retention secondary to buprenorphine administration.
AB  - Urinary retention is associated with buprenorphine, particularly with
      epidural/intrathecal delivery. However, it is rare with oral administration. This
      case report illustrates an occurrence of acute urinary retention after initiation
      of oral buprenorphine/naloxone.

PMID- 24126025
TI  - Benign acute childhood myositis--a rare cause of abnormal gait.
AB  - Benign acute childhood myositis is a rare postviral myositis seen in school-aged
      children after a common upper respiratory infection (URI), most commonly caused
      by influenza [J Microbiol Immunol Infect 2004;37:95-98]. Predominantly seen in
      boys, this condition causes bilateral calf tenderness and pain with ambulation,
      often presenting as a refusal to bear weight. To avoid activation within the
      gastroc-soleus complex, the child will frequently compensate with a "Frankenstein
      gait," described as a stiff-legged posture with shuffling gait [CMAJ 2009;181:711
      713]. The child may also walk on his toes or refuse to walk at all. This refusal
      to bear weight can be alarming to both providers and parents, resulting in
      extensive workups. We present the case of a 5-year-old boy who presented to the
      emergency department with a chief complaint of leg pain and refusal to walk.
      Further history revealed a resolved URI approximately 5 days prior. He was noted
      to have an elevated creatinine kinase with no evidence of renal insufficiency. He
      had no progression or complications, and his symptoms resolved spontaneously with
      minimal supportive treatment. Benign acute childhood myositis should be
      considered within the broad differential that surrounds a limping child or one
      who refuses to bear weight. Having insight into the condition with its
      characteristic gait abnormalities and associated URI history can often prevent
      extensive workups and be treated supportively in the outpatient setting.

PMID- 24126027
TI  - An evidence-based checklist to assess neuropsychological outcomes of epilepsy
      surgery: how good is the evidence?
AB  - PURPOSE: We aimed to assess the quality of evidence on neuropsychological
      outcomes after epilepsy surgery (ES). Accordingly, we created an evidence-based
      neuropsychology (EBNP) checklist to assess neuropsychological outcomes and
      applied this tool to studies from a systematic review. METHODS: The EBNP
      checklist was created using clinical expert input, scale development methodology
      for item generation and reduction and inter-rater reliability, and critical
      appraisal guidelines for studies about treatment. The checklist was applied to
      articles obtained through a systematic review of resective ES neuropsychological
      outcomes. The proportion of studies fulfilling the quality criteria and the total
      quality score were used to assess the quality of the evidence. RESULTS: An
      initial 45-item checklist was applied to 147 articles, with excellent inter-rater
      agreement (kappa=0.80). The mean quality score was 23 (SD: 4, range: 12-33).
      There was substantial variability in the percentage of studies meeting the
      criteria for specific items (0-99%). The median proportion of papers fulfilling
      various quality criteria was 1.4% for items related to group comparisons, 37% for
      clinical applicability, 67% for patient description, 78% for outcome assessment,
      and 91% for interventions. Higher quality correlated with longitudinal design,
      reporting presurgical IQ, seizure frequency and antiepileptic drugs, and using
      validated measures of change in individual patients. The final EBNP checklist
      consisted of 19 items. DISCUSSION: The EBNP checklist reliably identified quality
      strengths and threats to validity of neuropsychological outcome studies in ES.
      Studies would be most improved by the inclusion of random allocation to
      interventions or at minimum blinded outcome assessment, empirically based
      measures of reliable change and completeness of reporting of follow-up.

PMID- 24126026
TI  - Consciousness of seizures and consciousness during seizures: are they related?
AB  - Recent advances have been made in the network mechanisms underlying impairment of
      consciousness during seizures. However, less is known about patient awareness of
      their own seizures. Studying patient reports or documentation of their seizures
      is currently the most commonly utilized mechanism to scientifically measure
      patient awareness of seizures. The purpose of this review is to summarize the
      available evidence regarding the accuracy of patient seizure counts and identify
      the variables that may influence unreliable seizure reporting. Several groups
      looking at patient documentation of seizures during continuous EEG monitoring
      show that patients do not report as many as 50% of their seizures. These studies
      also suggest that seizures accompanied by loss of consciousness, arising from the
      left hemisphere or the temporal lobe, or occurring during sleep are associated
      with significantly reduced reporting. Baseline memory performance does not appear
      to have a major influence on the accuracy of seizure report. Further prospective
      studies using validated ictal behavioral testing as well as using correlation
      with newer electrophysiological and neuroimaging techniques for seizure
      localization are needed to more fully understand the mechanisms of underreporting
      of seizures. Better methods to alert caregivers about unrecognized seizures and
      to improve seizure documentation are under investigation.

PMID- 24126028
TI  - Health-related quality of life in adolescents with psychogenic nonepileptic
      seizures.
AB  - The aim of this study was to evaluate the health-related quality of life (HRQoL)
      in adolescents with psychogenic nonepileptic seizures (PNESs) and to identify
      factors affecting the quality of life in these patients. Thirty-four adolescents
      with PNESs were compared to 30 adolescents without any psychiatric disorder. The
      Schedule for Affective Disorders and Schizophrenia for School-Age Children,
      Present and Lifetime Version (K-SADS-PL) was applied to determine comorbid
      psychiatric disorders in the study group and to rule out any psychiatric disorder
      in the control group. The Pediatric Quality-of-Life Inventory (PedsQL) was used
      to assess the HRQoL. Physical HRQoL and psychosocial HRQoL, including emotional
      and school functioning, were found to be significantly lower in adolescents with
      PNESs. In the group with PNESs, the physical HRQoL and total HRQoL of adolescents
      with somatoform disorders other than PNESs and the emotional functioning of
      adolescents with major depressive disorder were worse than those of the
      adolescents without these comorbid psychiatric disorders. Seizure frequency and
      the duration of symptoms were not correlated with HRQoL scores. Treatment
      strategies in adolescents with PNESs should regard comorbid unexplained somatic
      symptoms and psychiatric disorders in addition to the reduction or cessation of
      seizures. 

PMID- 24126029
TI  - Deep brain stimulation in intractable epilepsy: postulated optimal stimulation
      parameters.

PMID- 24126030
TI  - Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin
      C type.
AB  - OBJECTIVE: To describe the long-term ophthalmologic outcomes of patients with
      methylmalonic aciduria and homocystinuria, cobalamin C type (cblC). DESIGN:
      Retrospective case series. PARTICIPANTS: All patients with cblC referred to the
      Department of Ophthalmology of the Centre Hospitalier Universitaire Sainte
      Justine from 1984 through 2012 were studied. Twelve such patients were
      identified. METHODS: Clinical ophthalmic examinations, neuroimaging,
      electroretinography, and the results of MMACHC mutation analysis were reviewed
      retrospectively. MAIN OUTCOME MEASURES: We examined visual acuity, ocular
      alignment, presence of maculopathy and peripheral retinopathy, optic atrophy, and
      nystagmus. Photopic and scotopic electroretinograms were reviewed. We examined
      and compared mutations in the MMACHC gene. Neuroimaging abnormalities were
      compiled when available. RESULTS: Twelve cblC patients were followed up from 2 to
      23 years (average, 10 years). Eleven of 12 patients were diagnosed before the age
      of 1 year (range, birth-2 years). An initial ophthalmic examination was performed
      within the first year of age in 9 of 12 patients. Visual acuity at the time of
      presentation was variable, ranging from light perception to 20/20. Visual acuity
      was worse than 20/100 in 75% (9/12) of patients at last follow-up. Eight patients
      (67%) had obvious maculopathy on fundus examination. Other findings included
      peripheral retinopathy (8/12 [67%]), nystagmus (8/12 [67%]), strabismus (5/12
      [42%]), and optic atrophy (6/12 [50%]). Funduscopic deterioration was documented
      in 1 patient, whereas electrophysiologic changes occurred in 4 patients.
      Neuroimaging results were available in 7 of the patients, revealing corpus
      callosum atrophy (7/7 [100%]) and periventricular white matter loss (6/7 [85%]).
      CONCLUSIONS: Most children in our series had early-onset disease with neurologic
      manifestations and abnormal ophthalmologic examination results. Despite early
      treatment, many early-onset cblC patients have poor visual function.

PMID- 24126031
TI  - Congenital hypertrophy of the retinal pigment epithelium: enhanced-depth imaging
      optical coherence tomography in 18 cases.
AB  - OBJECTIVE: To describe the imaging characteristics of congenital hypertrophy of
      the retinal pigment epithelium (CHRPE). DESIGN: Retrospective, observational case
      series. PARTICIPANTS: Eighteen eyes of 18 patients with CHRPE. METHODS: Review of
      chart, fundus photography, ultrasonography, fundus autofluorescence, infrared
      reflectance (IR) imaging, and enhanced-depth imaging optical coherence tomography
      (EDI-OCT). MAIN OUTCOME MEASURES: Features of CHRPE as analyzed by EDI-OCT.
      RESULTS: The mean age at diagnosis was 48 years (range, 13-73 years). There were
      5 males and 13 females, and 17 Caucasian and 1 African American patients. The
      mean best-corrected visual acuity was 20/22 (range, 20/20-20/40). The CHRPE was
      located in the retinal periphery (n = 16) with intralesional lacunae (n = 14) and
      surrounding nonpigmented (n = 4) and pigmented (n = 14) halo. By ultrasonography,
      the mean CHRPE thickness was 1.0 mm (range, 0.9-1.4 mm). Fundus autofluorescence
      disclosed hypoautofluorescence (n = 18) with lacunae (n = 14) showing
      isoautofluorescence (n = 10) or hypoautofluorescence (n = 4). Infrared
      reflectance imaging displayed hyporeflectivity in the area of pigmentation (n =
      16) and hyperreflectivity within lacunae (n = 14). On EDI-OCT, all 18 lesions
      were flat with a mean basal diameter of 4529 MUm (median, 3707 MUm; range, 697-11
      617 MUm). The mean central sublesional choroidal thickness (126.4 MUm) was not
      different compared with thickness 50 MUm outside the margin (126.8 MUm; P =
      0.99). The retinal pigment epithelium (RPE) was absent (n = 2), thickened (n =
      16), or irregular (n = 15). Of 9 lesions in which lacunae were imaged, 8 showed
      absent RPE. The overlying retinal findings included thinning or absence of the
      outer retina beginning at the ganglion cell layer (n = 1), outer plexiform layer
      (n = 4), outer nuclear layer (n = 12), or inner segment/outer segment junction (n
      = 1). Additional retinal findings included hyperreflective spots (n = 11),
      cystoid edema (n = 5), and subretinal cleft (n = 6). Subretinal cleft
      specifically occurred at the site of absent photoreceptors. CONCLUSIONS:
      Generally, CHRPE displays hypoautoflouorescence and hyporeflectivity with
      hyperreflective lacunae on IR imaging. On EDI-OCT, CHRPE seems flat with
      thickened, irregular RPE and absent RPE within lacunae. A prominent feature is
      outer retinal loss, generally involving the outer nuclear layer to
      photoreceptors, occasionally with a characteristic subretinal cleft.

PMID- 24126032
TI  - The United Kingdom Glaucoma Treatment Study: a multicenter, randomized, double
      masked, placebo-controlled trial: baseline characteristics.
AB  - OBJECTIVE: The United Kingdom Glaucoma Treatment Study (UKGTS) tests the
      hypothesis that treatment with a topical prostaglandin analog, compared with
      placebo, reduces the frequency of visual field (VF) deterioration events in
      patients with open-angle glaucoma (OAG) by 50% over a 2-year period. Additional
      goals are to evaluate study power with novel clinical trial outcomes: (1) VF
      deterioration velocity and (2) VF and quantitative imaging measurements modeled
      as joint outcomes. DESIGN: The UKGTS is a randomized, double-masked, placebo
      controlled, multicenter treatment trial for OAG. PARTICIPANTS: A total of 516
      patients with newly diagnosed (previously untreated) OAG were prospectively
      recruited at 10 UK centers between 2007 and 2010. METHODS: Eligible patients were
      randomly assigned to treatment with latanoprost 0.005% or placebo. The
      observation period was 2 years, with subjects monitored by VF testing,
      quantitative imaging, optic disc photography, and tonometry at 11 visits. MAIN
      OUTCOME MEASURES: The primary outcome measure is time to VF deterioration within
      24 months. Secondary outcomes include the deterioration velocity of VF and
      quantitative imaging measures. RESULTS: The main source of referrals was
      optometrists (88%). A total of 777 subjects were assessed for eligibility, and
      261 were excluded because they did not meet the inclusion criteria or declined to
      participate. The mean age of the 516 participants was 66 years, and 52.9% were
      male; 90.1% of the participants were white, and approximately one third (32.2%)
      reported a family history of glaucoma. A total of 777 eyes were eligible at
      initial assessment. Both eyes were eligible for 265 participants. Mean (standard
      deviation) intraocular pressure (IOP) at baseline for the eyes with better versus
      worse mean deviation (MD) was 18.9 (4.1) and 19.9 (4.7) mmHg, respectively (P =
      0.0053). Some 56.1% of all eligible eyes had IOP <20 mmHg at baseline. The median
      (interquartile range) VF MD for all eligible eyes was -2.9 dB (-1.6 to -4.8 dB).
      CONCLUSIONS: This is the first randomized, placebo-controlled trial to evaluate
      the efficacy of medical treatment in reducing VF deterioration in OAG. The
      baseline characteristics for eligible patients and eyes from this cohort are
      presented and compared with those of previous trials. The baseline
      characteristics are similar to those of the largely population-based Early
      Manifest Glaucoma Trial. The early stage of the glaucoma and relatively low IOP
      at diagnosis suggest remarkably sensitive case findings by community optometrists
      in the United Kingdom.

PMID- 24126033
TI  - Skin lesions in anti-Pm-Scl-70 positive systemic sclerosis-dermatomyositis
      overlap syndrome improve during local PUVA phototherapy.

PMID- 24126034
TI  - Image formation mechanisms of spherical aberration corrected BF STEM imaging
      methods.
AB  - In this study, we explore the formation mechanisms of different spherical
      aberration (C(s))-corrected bright-field (BF) scanning transmission electron
      microscope (STEM) imaging methods. The C(s)-corrected BF STEM imaging modes are
      characterised in detail using simulated images and experimental BF STEM images
      obtained with several types of detectors. The Co3O4 specimen results show that
      the occupancy, the atomic spacing, and the atomic number of the atoms
      constituting the atomic columns control image formation in BF STEM imaging, which
      is used to detect light atomic columns. The middle-angle BF STEM image is crucial
      in image formation by BF STEM imaging.

PMID- 24126035
TI  - Poly(meth)acrylate-based coatings.
AB  - Poly(meth)acrylate coatings for pharmaceutical applications were introduced in
      1955 with the launch of EUDRAGIT((r)) L and EUDRAGIT((r)) S, two types of anionic
      polymers. Since then, by introducing various monomers into their polymer chains
      and thus altering their properties, diverse forms with specific characteristics
      have become available. Today, poly(meth)acrylates function in different parts of
      the gastrointestinal tract and/or release the drug in a time-controlled manner.
      This article reviews the properties of various poly(meth)acrylates and discusses
      formulation issues as well as application possibilities. 

PMID- 24126036
TI  - Progress in film coating.

PMID- 24126037
TI  - Stability of aqueous polymeric controlled release film coatings.
AB  - Aqueous polymeric film coatings provide a great potential to accurately control
      the release rate of a drug from a pharmaceutical dosage form, while avoiding the
      various disadvantages associated with the use of organic solvents. However, long
      term instability of drug release, due to imperfect film formation during coating
      and curing, can be a serious concern. If the coalescence of the particles
      continues during storage, the film permeability can decrease, slowing down drug
      release. Different strategies can be used to effectively avoid this phenomenon,
      including optimized curing conditions, the addition of appropriate additives and
      the use of specific packaging materials. This article gives an overview on the
      current state of the art in this field. Various practical examples are described,
      covering different types of polymer coatings and drugs. The aims are: (i) to
      provide a better understanding of the release patterns and potential changes
      thereof, and (ii) to help identifying strategies allowing for improved long term
      stability for specific types of polymer coatings. 

PMID- 24126038
TI  - A novel lactoferrin-modified beta-cyclodextrin nanocarrier for brain-targeting
      drug delivery.
AB  - The blood-brain barrier (BBB) restricts the transfer and delivery of most drug
      substances to brain. In this study, a novel nano-drug delivery system for brain
      targeting was developed and investigated in vitro and in vivo. Lactoferrin (Lf)
      was selected as a brain-targeting ligand and conjugated to beta-cyclodextrin
      (beta-CD) via the heterobifunctional polyethyleneglycol (PEG) linker NHS-PEG-MAL,
      yielding Lf conjugated beta-cyclodextrin (Lf-CD). UV-vis, FTIR, NMR and
      transmission electron microscopy (TEM) techniques clearly demonstrated the
      successful synthesis of Lf-CD nanoparticles with the average diameter of 92.9 +/-
      16.5 nm. Using near-infrared fluorescent dye IR-775 chloride (IR) as a model
      compound of poorly water-soluble drugs, IR-loaded Lf-CD nanoparticles (Lf-CD/IR)
      were successfully prepared with a high entrapment efficiency of 98.1 +/- 4.8%.
      Biodistribution and pharmacokinetics of Lf-CD/IR were evaluated in KM mice after
      intravenous administration. The results of tissue distribution studies revealed
      that Lf-CD/IR treatment showed greatly improved BBB transport efficiency. In
      addition, AUC0-2h of IR in brain after Lf-CD/IR treatment was seven fold higher
      compared with that of IR treatment without Lf-CD nano-carriers, demonstrating
      that the introduction of Lf-CD drug-delivery system positively resulted in a
      higher AUC located in brain tissue. These results provide evidence that Lf-CD
      nanoparticles could be exploited as a potential brain-targeting drug delivery
      system for hydrophobic drugs and diagnostic reagents which normally fail to pass
      through the BBB.

PMID- 24126039
TI  - Hypertensive posterior reversible encephalopathy syndrome causing posterior fossa
      edema and hydrocephalus.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a well characterized
      entity resulting from the inability of cerebral autoregulation to adequately
      protect the brain from uncontrolled hypertension. It primarily affects the
      occipital lobes, but can also involve the structures in the posterior fossa
      including the brainstem and cerebellum. Treatment usually consists of strict
      blood pressure control, but more aggressive management may be indicated with
      acutely worsening neurological status. We present a patient with hypertensive
      encephalopathy that resulted in hydrocephalus and brainstem compression
      necessitating surgical decompression requiring ventriculostomy and suboccipital
      craniectomy. In rare cases, PRES can present with severe brainstem compression
      requiring emergent posterior fossa decompression. When brainstem signs are
      present on exam, emergent posterior fossa decompression may be safer than
      ventriculostomy alone. 

PMID- 24126040
TI  - Autoimmune retinopathy associated with carcinoid tumour of the small bowel.
AB  - Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic
      condition associated with vision loss. It has been associated with a variety of
      systemic malignancies. The primary clinical presentation is rapid, progressive
      vision loss. Rod and cone dysfunction can cause other associated symptoms, such
      as nyctalopia. Electrophysiological testing and detection of anti-retinal
      antibodies are used to confirm the diagnosis. To our knowledge we describe the
      first patient with CAR associated with a carcinoid tumour of the gastrointestinal
      system. Auto-antibodies against alpha enolase and carbonic anhydrase II were
      detected with western blotting. Electroretinogram findings were consistent with
      rod and cone dysfunction. 

PMID- 24126041
TI  - Quantitative gait analysis of long-term locomotion deficits in classical
      unilateral striatal intracerebral hemorrhage rat model.
AB  - Gait analysis is a systematic collection of quantitative information on bodily
      movements during locomotion. Gait analysis has been employed clinically in stroke
      patients for their rehabilitation planning. In animal studies, gait analysis has
      been employed for the assessment of their locomotive disturbances in ischemic
      stroke, spinal cord injury and Parkinson's disease. The aims of the work reported
      here were to identify the gait parameters, collected from the computer-generated
      CatWalk System, that change after unilateral intracerebral hemorrhage (ICH) in
      the acute stage and long term up to 56 days post-ICH. The results showed that
      with the collagenase-induced unilateral striatal lesion, the rats displayed a
      significant contralateral decrease in print and maximum contact area and paw
      intensity, a diagonal increase in the stance duration of the left front and right
      hind paws, a significant decrease in the stride length of all four limbs, and
      foot pattern instability as reflected by the base of support, support on styles,
      and cadence. These deficits, including those in print area, stance and pressure,
      were demonstrated throughout the long-term period following ICH. The correlations
      between the gait parameters, lesion volume and asymmetrical forelimb use were
      also reported in this paper. This work has provided a systematic description on
      gait parameters in the classical striatal ICH model, which might become an
      essential assessment tool in future studies of pathophysiology and the
      development of novel treatments for experimental unilateral intracerebral
      hemorrhage with gait deficits. 

PMID- 24126043
TI  - Emotion recognition abilities across stimulus modalities in schizophrenia and the
      role of visual attention.
AB  - Emotion can be expressed by both the voice and face, and previous work suggests
      that presentation modality may impact emotion recognition performance in
      individuals with schizophrenia. We investigated the effect of stimulus modality
      on emotion recognition accuracy and the potential role of visual attention to
      faces in emotion recognition abilities. Thirty-one patients who met DSM-IV
      criteria for schizophrenia (n=8) or schizoaffective disorder (n=23) and 30 non
      clinical control individuals participated. Both groups identified emotional
      expressions in three different conditions: audio only, visual only, combined
      audiovisual. In the visual only and combined conditions, time spent visually
      fixating salient features of the face were recorded. Patients were significantly
      less accurate than controls in emotion recognition during both the audio and
      visual only conditions but did not differ from controls on the combined
      condition. Analysis of visual scanning behaviors demonstrated that patients
      attended less than healthy individuals to the mouth in the visual condition but
      did not differ in visual attention to salient facial features in the combined
      condition, which may in part explain the absence of a deficit for patients in
      this condition. Collectively, these findings demonstrate that patients benefit
      from multimodal stimulus presentations of emotion and support hypotheses that
      visual attention to salient facial features may serve as a mechanism for accurate
      emotion identification.

PMID- 24126044
TI  - Asking Questions and Appreciating Inquiry: A Winning Strategy for the Nurse
      Educator and Professional Nurse Learner.

PMID- 24126042
TI  - Using a simple HPLC approach to identify the enzymatic products of UTL-5g, a
      small molecule TNF-alpha inhibitor, from porcine esterase and from rabbit
      esterase.
AB  - UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity,
      nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-alpha
      inhibition among other factors. As a prelude to investigating the metabolites of
      UTL-5g, we set out to identify the enzymatic products of UTL-5g under the
      treatment of both porcine liver esterase (PLE) and rabbit liver esterase (RLE).
      First, a number of mixtures made by UTL-5g and PLE were incubated at 25 degrees
      C. At predetermined time points, individual samples were quenched by
      acetonitrile, vortexed, and centrifuged. The supernatants were then analyzed by
      reversed-phase HPLC (using a C18 column). The retention times and UV/vis spectra
      of individual peaks were compared to those of UTL-5g and its two postulated
      enzymatic products; thus the enzymatic products of UTL-5g were tentatively
      identified. Secondly, a different HPLC method (providing different retentions
      times) was used to cross-check and to confirm the identities of the two enzymatic
      products. Based on the observations, it was concluded that under the treatment of
      PLE, the major enzymatic products of UTL-5g were 5-methyliosxazole-3-carboxylic
      acid (ISOX) and 2,4-dichloroaniline (DCA). Treatment of UTL-5g by RLE also
      provided the same enzymatic products of UTL-5g from esterase. These results
      indicate that the peptide bond in UTL-5g was cleaved by PLE/RLE. Michaelis-Menten
      kinetics showed that the Km values of UTL-5g were 2.07mM with PLE and 0.37mM with
      RLE indicating that UTL-5g had a higher affinity with RLE. In summary, by a
      simple HPLC approach, we have concluded that the peptide bond in UTL-5g was
      cleaved by esterase from either porcine liver or rabbit liver in vitro and
      afforded DCA (at a mole ratio of 1:1) and ISOX. However, further studies are
      needed in order to determine whether UTL-5g is metabolized by microsomal enzymes
      to produce ISOX and DCA. 

PMID- 24126045
TI  - Legislative advocacy: evaluation of a grand rounds intervention for
      pediatricians.
AB  - OBJECTIVE: To evaluate the impact of a Grand Rounds Action Alert (GRAA)
      intervention on the behaviors, knowledge, and attitudes of pediatric grand rounds
      (GR) attendees; and to assess its acceptability. METHODS: A cross-sectional,
      quasi-experimental study was performed at a freestanding children's hospital.
      GRAA on child health legislative topics were presented in the first 2 minutes of
      the pediatric GR session as well as posted outside. Each session included an
      action item, such as writing/signing letters to elected officials or
      informational sheets with legislator contact information. Main outcome measures
      included self-reported behavior, advocacy knowledge, attitudes, and
      acceptability. RESULTS: One year after GRAA implementation, GR attendees with
      high exposure to the intervention were more likely to have written/signed a
      letter to a legislator compared to those with low/no exposure (60% vs 35%, P =
      .016). Those with high exposure were also more knowledgeable regarding financing
      of health care for low-income children (20% vs 5%, P = .027). Attitudes toward
      advocacy at baseline were positive: respondents agreed it is important to remain
      informed about (98%) and advocate for (94%) legislation favorable to children's
      health. Implementing this program was challenging, but the intervention was
      accepted favorably: 93% of respondents agreed that GRAA should continue.
      CONCLUSIONS: GRAA facilitated participation in legislative advocacy behaviors
      while improving self-perceived knowledge of legislative issues relating to
      children's health. They were well received in a large tertiary children's
      hospital.

PMID- 24126046
TI  - Developing a quality and safety curriculum for fellows: lessons learned from a
      neonatology fellowship program.
AB  - Formal training in health care quality and safety has become an important
      component of medical education at all levels, and quality and safety are core
      concepts within the practice-based learning and system-based practice medical
      education competencies. Residency and fellowship programs are rapidly attempting
      to incorporate quality and safety curriculum into their training programs but
      have encountered numerous challenges and barriers. Many program directors have
      questioned the feasibility and utility of quality and safety education during
      this stage of training. In 2010, we adopted a quality and safety educational
      module in our neonatal fellowship program that sought to provide a robust and
      practical introduction to quality improvement and patient safety through a
      combination of didactic and experiential activities. Our module has been
      successfully integrated into the fellowship program's curriculum and has been
      beneficial to trainees, faculty, and our clinical services, and our experience
      suggests that fellowship may be particularly well suited to incorporation of
      quality and safety training. We describe our module and share tools and lessons
      learned during our experience; we believe these resources will be useful to other
      fellowship programs seeking to improve the quality and safety education of their
      trainees. 

PMID- 24126047
TI  - Imaging and histological characterization of a human brain xenograft in pig: the
      first induced glioma model in a large animal.
AB  - The prognosis of glioblastoma remains poor despite significant improvement in
      cytoreductive surgery, external irradiation and new approach of systemic
      treatment as antiangiogenic therapy. One of the issues is the low concentration
      in the infiltrated parenchyma of therapeutic agent administered intravenously
      mainly due to the blood-brain barrier. An intracerebral injection is advocated to
      overpass this barrier, this kind of administration need a low flow and continuous
      injection. The development of sophisticated implanted devices for convection
      enhanced delivery is a mandatory step to have a controlled released of a
      therapeutic agent in glioblastoma treatment. Before testing such a device in a
      clinical trial a serious preclinical studies are required, in order to test it in
      realistic conditions we have develop the first induced high grade glioma model in
      a non-rodent animal: the pig. 21 pigs have been implanted in the parietal lobe
      with human glioblastoma cell lineage under a chemical immunosuppression by
      ciclosporine. A MRI follow up was then realized. 15 pigs have been implanted with
      U87MG, 14 have presented a macroscopic significant tumor, with radiological and
      anatomapathological characteristics of high grade glioma. 6 pigs were implanted
      with G6, stem-like cells tumors of glioblastoma, 1 pig develops a macroscopic
      tumor. This is the first reproducible glioma model in a large animal described,
      it open the way to preclinical studies to test implanted devices in anatomic
      realistic conditions, without the ethical issues of a primate use. 

PMID- 24126048
TI  - Practical approaches to vaccine hesitancy issues in the United States: 2013.
AB  - The intention to delay or avoid vaccines that are recommended by the Advisory
      Committee on Immunization Practices can be described as "vaccine hesitancy."
      While outright refusal of all vaccines is uncommon, hesitancy is seen on a
      regular basis in most primary care offices, resulting in immunization delay and
      prolonged susceptibility to preventable disease. The consequences of vaccine
      hesitancy include the potential for resurgence of vaccine preventable infections.
      Open, honest, and frank discussions with hesitant patients and their families can
      assist in their understanding of the importance of vaccines. While many
      experienced providers are able to do so in an intuitive manner, others may
      benefit from developing a systemic framework for such discussions. An
      understanding of the history and rationale for vaccine hesitancy is a first step
      in regaining lost public confidence in our robust immunization programs. 

PMID- 24126049
TI  - In vitro characterization of acid secretion in the gilthead sea bream (Sparus
      aurata) stomach.
AB  - The gastric acid secretion of juvenile Sparus aurata was characterized in Ussing
      chambers; secretion rates were determined by a pH-stat method at pH5.50 and
      bioelectrical parameters were measured in current-clamped tissues. The basal
      secretion equaled to 535+/-87nmol.cm(-2).h(-1). Serosal carbachol 100MUM produced
      an increase (DeltaJH(+)) of 725+/-133nmol.cm(-2).h(-1) from basal secretion, this
      effect being inhibited by mucosal omeprazole 100MUM. Basal secretion was also
      sensitive to the combination of serosal forskolin (FK) 10MUM+serosal
      isobutylmethylxanthine (IBMX) 100MUM (DeltaJH(+)=793+/-239nmol.cm(-2).h(-1));
      this effect was insensitive to mucosal omeprazole 100mM but inhibited by mucosal
      bafilomycin A1 100nM. The effect of carbachol proceeded within a few minutes
      (<10min), whereas the effect of FK+IBMX was gradual, taking 40min to reach the
      maximum. The addition of mucosal gadolinium (Gd(3+)) 100MUM, a potent calcium
      sensing receptor (CaR) agonist, stimulated the basal secretion (DeltaJH(+)=340+/
      81nmol.cm(-2).h(-1)). The present results indicate that the acid secretion
      mechanism in the sea bream stomach is regulated by muscarinic and CaR-like
      receptors, cAMP is implicated in the signal transduction, and at least two proton
      pumps, a HK-ATPase and a V-ATPase contribute to acid secretion. 

PMID- 24126050
TI  - Genetic variation in niche construction: implications for development and
      evolutionary genetics.
AB  - Niche construction occurs when the traits of an organism influence the
      environment that it experiences. Research has focused on niche-constructing
      traits that are fixed within populations or species. However, evidence
      increasingly demonstrates that niche-constructing traits vary among genotypes
      within populations. Here, we consider the potential implications of genetic
      variation in niche construction for evolutionary genetics. Specifically, genetic
      variation in niche-constructing traits creates a correlation between genotype and
      environment. Because the environment influences which genes and genetic
      interactions underlie trait variation, genetic variation in niche construction
      can alter inferences about the heritability, pleiotropy, and epistasis of traits
      that are phenotypically plastic. The effects of niche construction on these key
      evolutionary parameters further suggest novel ways by which niche construction
      can influence evolution. 

PMID- 24126051
TI  - A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in
      African trypanosomes.
AB  - The genes for all cytoplasmic and potentially all mitochondrial aminoacyl-tRNA
      synthetases (aaRSs) were identified, and all those tested by RNA interference
      were found to be essential for the growth of Trypanosoma brucei. Some of these
      enzymes were localized to the cytoplasm or mitochondrion, but most were dually
      localized to both cellular compartments. Cytoplasmic T. brucei aaRSs were
      organized in a multiprotein complex in both bloodstream and procyclic forms. The
      multiple aminoacyl-tRNA synthetase (MARS) complex contained at least six aaRS
      enzymes and three additional non-aaRS proteins. Steady-state kinetic studies
      showed that association in the MARS complex enhances tRNA-aminoacylation
      efficiency, which is in part dependent on a MARS complex-associated protein
      (MCP), named MCP2, that binds tRNAs and increases their aminoacylation by the
      complex. Conditional repression of MCP2 in T. brucei bloodstream forms resulted
      in reduced parasite growth and infectivity in mice. Thus, association in a MARS
      complex enhances tRNA-aminoacylation and contributes to parasite fitness. The
      MARS complex may be part of a cellular regulatory system and a target for drug
      development. 

PMID- 24126052
TI  - Hyperthermia stress activates heat shock protein expression via propyl isomerase
      1 regulation with heat shock factor 1.
AB  - Heat shock proteins (HSPs), which are members of the chaperone family of
      proteins, are essential factors for cellular responses to environmental
      stressors, such as hyperthermia, and are antiapoptotic. The transcription of HSPs
      is mainly controlled by heat shock transcription factor 1 (HSF1). In response to
      environmental stress, HSF1 forms a trimer, undergoes hyperphosphorylation, and is
      translocated to the nucleus. In this study, we show that upon heat shock
      treatment of cells, a WW domain-containing propyl-isomerase, PIN1, is able to
      colocalize to and associate with phospho-HSF1 at Ser(326) in the nucleus via its
      WW domain. This interaction is required for the DNA-binding activity of HSF1 and
      is consistent with the lower induction of HSPs in PIN1-deficient cells. This
      function of PIN1 is further demonstrated by in vivo refolding and survival
      assays, which have shown that PIN1-deficient cells are temperature sensitive and
      develop apoptosis upon exposure to an environmental challenge. Moreover, the
      reduced levels of HSPs in PIN1-deficient cells resulted in less efficient
      refolding of denatured proteins. Based on our results, we propose a novel role
      for PIN1 whereby it acts as a stress sensor regulating HSF1 activity in response
      to stress on multiple levels through the transcriptional activation of stress
      response elements in embryonic fibroblast cells, tumor cells, and neurons. 

PMID- 24126053
TI  - The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and
      ROCK activities to promote polarized-cancer-cell migration.
AB  - The role of RhoA in promoting directed cell migration has been complicated by
      studies showing that it is activated both in the front and the rear of migrating
      cells. We report here that the RhoA-specific guanine nucleotide exchange factor
      Syx is required for the polarity of actively migrating brain and breast tumor
      cells. This function of Syx is mediated by the selective activation of the RhoA
      downstream effector Dia1, the subsequent reorganization of microtubules, and the
      downregulation of focal adhesions and actin stress fibers. The data argue that
      directed cell migration requires the precise spatiotemporal regulation of Dia1
      and ROCK activities in the cell. The recruitment of Syx to the cell membrane and
      the subsequent selective activation of Dia1 signaling, coupled with the
      suppression of ROCK and activation of cofilin-mediated actin reorganization,
      plays a key role in establishing cell polarity during directed cell migration. 

PMID- 24126054
TI  - Human cells have a limited set of tRNA anticodon loop substrates of the tRNA
      isopentenyltransferase TRIT1 tumor suppressor.
AB  - Human TRIT1 is a tRNA isopentenyltransferase (IPTase) homologue of Escherichia
      coli MiaA, Saccharomyces cerevisiae Mod5, Schizosaccharomyces pombe Tit1, and
      Caenorhabditis elegans GRO-1 that adds isopentenyl groups to adenosine 37 (i6A37)
      of substrate tRNAs. Prior studies indicate that i6A37 increases translation
      fidelity and efficiency in codon-specific ways. TRIT1 is a tumor suppressor whose
      mutant alleles are associated with cancer progression. We report the systematic
      identification of i6A37-containing tRNAs in a higher eukaryote, performed using
      small interfering RNA knockdown and other methods to examine TRIT1 activity in
      HeLa cells. Although several potential substrates contained the IPTase
      recognition sequence A36A37A38 in the anticodon loop, only tRNA(Ser)AGA,
      tRNA(Ser)CGA, tRNA(Ser)UGA, and selenocysteine tRNA with UCA (tRNA([Ser]Sec)UCA)
      contained i6A37. This subset is a significantly more restricted than that for two
      distant yeasts (S. cerevisiae and S. pombe), the only other organisms
      comprehensively examined. Unlike the fully i6A37-modified tRNAs for Ser,
      tRNA([Ser]Sec)UCA is partially (~40%) modified. Exogenous selenium and other
      treatments that decreased the i6A37 content of tRNA([Ser]Sec)UCA led to increased
      levels of the tRNA([Ser]Sec)UCA. Of the human mitochondrion (mt)-encoded tRNAs
      with A36A37A38, only mt tRNAs tRNA(Ser)UGA and tRNA(Trp)UCA contained detectable
      i6A37. Moreover, while tRNA(Ser) levels were unaffected by TRIT1 knockdown, the
      tRNA([Ser]Sec)UCA level was increased and the mt tRNA(Ser)UGA level was
      decreased, suggesting that TRIT1 may control the levels of some tRNAs as well as
      their specific activity. 

PMID- 24126055
TI  - KLF5 activates microRNA 200 transcription to maintain epithelial characteristics
      and prevent induced epithelial-mesenchymal transition in epithelial cells.
AB  - KLF5 is an essential basic transcriptional factor that regulates a number of
      physiopathological processes. In this study, we tested whether and how KLF5
      modulates the epithelial-mesenchymal transition (EMT). Using transforming growth
      factor beta (TGF-beta)- and epidermal growth factor (EGF)-treated epithelial
      cells as an established model of EMT, we found that KLF5 was downregulated during
      EMT and that knockdown of KLF5 induced EMT even in the absence of TGF-beta and
      EGF treatment, as indicated by phenotypic and molecular EMT properties. Array
      based screening suggested and biochemical analyses confirmed that the microRNA
      200 (miR-200) microRNAs, a group of well-established EMT repressors, were
      transcriptionally activated by KLF5 via its direct binding to the GC boxes in miR
      200 gene promoters. Functionally, overexpression of miR-200 prevented the EMT
      induced by KLF5 knockdown or by TGF-beta and EGF treatment, and ectopic
      expression of KLF5 attenuated TGF-beta- and EGF-induced EMT by rescuing the
      expression of miR-200. In mouse prostates, knockout of Klf5 downregulated the miR
      200 family and induced molecular changes indicative of EMT. These findings
      indicate that KLF5 maintains epithelial characteristics and prevents EMT by
      transcriptionally activating the miR-200 family in epithelial cells. 

PMID- 24126056
TI  - Histone H3K27 trimethylation inhibits H3 binding and function of SET1-like H3K4
      methyltransferase complexes.
AB  - Trimethylated histone H3 lysine 4 (H3K4) and H3K27 generally mark
      transcriptionally active and repressive chromatins, respectively. In most cell
      types, these two modifications are mutually exclusive, and this segregation is
      crucial for the regulation of gene expression. However, how this anticorrelation
      is achieved has not been fully understood. Here, we show that removal of the
      H3K27 trimethyl mark facilitates recruitment of SET1-like H3K4 methyltransferase
      complexes to their target genes by eliciting a novel interaction between histone
      H3 and two common subunits, WDR5 and RBBP5, of SET1-like complexes. Consistent
      with this result, H3K27 trimethylation destabilizes interactions of H3 with SET1
      like complexes and antagonizes their ability to carry out H3K4 trimethylation of
      peptide (H3 residues 1 to 36), histone octamer, and mononucleosome substrates.
      Altogether, our studies reveal that H3K27 trimethylation of histone H3 represses
      a previously unrecognized interaction between H3 and SET1-like complexes. This
      provides an important mechanism that directs the anticorrelation between H3K4 and
      H3K27 trimethylation. 

PMID- 24126057
TI  - Extracellular heat shock protein 90 signals through subdomain II and the NPVY
      motif of LRP-1 receptor to Akt1 and Akt2: a circuit essential for promoting skin
      cell migration in vitro and wound healing in vivo.
AB  - Normal cells secrete heat shock protein 90 alpha (Hsp90alpha) in response to
      tissue injury. Tumor cells have managed to constitutively secrete Hsp90alpha
      during invasion and metastasis. The sole function of extracellular Hsp90alpha
      (eHsp90alpha) is to promote cell motility, a critical event for both wound
      healing and tumor progression. The mechanism of promotility action by
      eHsp90alpha, however, has remained elusive. A key issue is whether eHsp90alpha
      still acts as a chaperone outside the cells or is a new and bona fide signaling
      molecule. Here, we have provided evidence that eHsp90alpha utilizes a unique
      transmembrane signaling mechanism to promote cell motility and wound healing.
      First, subdomain II in the extracellular part of low-density lipoprotein receptor
      related protein 1 (LRP-1) receives the eHsp90alpha signal. Then, the NPVY but not
      the NPTY motif in the cytoplasmic tail of LRP-1 connects eHsp90alpha signaling to
      serine 473 but not threonine 308 phosphorylation in Akt kinases. Individual
      knockdown of Akt1, Akt2, or Akt3 revealed the importance of Akt1 and Akt2 in
      eHsp90alpha-induced cell motility. Akt gene rescue experiments suggest that Akt1
      and Akt2 work in concert, rather than independently, to mediate eHsp90alpha
      promotility signaling. Finally, Akt1 and Akt2 knockout mice showed impaired wound
      healing that cannot be corrected by topical application with the eHsp90alpha
      protein. 

PMID- 24126058
TI  - hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1.
AB  - The NAD(+)-dependent deacetylase SirT1 regulates gene silencing and genomic
      stability in response to nutrient deprivation and DNA damage. An important
      regulator of SirT1 in mammalian cells is DBC1 (deleted in breast cancer 1;
      KIAA1967 or CCAR2), which binds to SirT1 and inhibits the deacetylation of
      substrates. Recent studies have revealed that ATM/ATR-mediated phosphorylation of
      DBC1 promotes binding to SirT1. Here we show that DBC1 is modified by acetylation
      on two N-terminal lysine residues (K112 and K215). The MYST family histone
      acetyltransferase hMOF (human MOF) is responsible for DBC1 acetylation.
      Acetylation of K112 and K215 inhibits DBC1-SirT1 binding and increases SirT1
      deacetylase activity. SirT1 also promotes DBC1 deacetylation, suggesting the
      presence of a negative-feedback mechanism that stabilizes the SirT1-DBC1 complex
      and limits SirT1 activity. hMOF binding and acetylation of DBC1 are inhibited
      after DNA damage in an ATM-dependent fashion, contributing to increased SirT1
      DBC1 binding after DNA damage. Furthermore, a DBC1 mutant that mimics the
      acetylated state fails to promote apoptosis after DNA damage. These results
      suggest that acetylation of DBC1 inhibits binding to SirT1 and serves as a
      mechanism that connects DNA damage signaling to SirT1 and cell fate
      determination. 

PMID- 24126059
TI  - CREB3L1 is a metastasis suppressor that represses expression of genes regulating
      metastasis, invasion, and angiogenesis.
AB  - The unfolded protein response (UPR) is activated in response to hypoxia-induced
      stress such as in the tumor microenvironment. This study examined the role of
      CREB3L1 (cyclic AMP [cAMP]-responsive element-binding protein 3-like protein 1),
      a member of the UPR, in breast cancer development and metastasis. Initial
      experiments identified the loss of CREB3L1 expression in metastatic breast cancer
      cell lines compared to low-metastasis or nonmetastatic cell lines. When
      metastatic cells were transfected with CREB3L1, they demonstrated reduced
      invasion and migration in vitro, as well as a significantly decreased ability to
      survive under nonadherent or hypoxic conditions. Interestingly, in an in vivo rat
      mammary tumor model, not only did CREB3L1-expressing cells fail to form
      metastases compared to CREB3L1 null cells but regression of the primary tumors
      was seen in 70% of the animals as a result of impaired angiogenesis. Microarray
      and chromatin immunoprecipitation with microarray technology (ChIP on Chip)
      analyses identified changes in the expression of many genes involved in cancer
      development and metastasis, including a decrease in those involved in
      angiogenesis. These data suggest that CREB3L1 plays an important role in
      suppressing tumorigenesis and that loss of expression is required for the
      development of a metastatic phenotype. 

PMID- 24126060
TI  - Over expression of PPP2R2C inhibits human glioma cells growth through the
      suppression of mTOR pathway.
AB  - PPP2R2C encodes a gamma isoform of the subunit B55 subfamily, which is a
      regulatory subunit of Protein phosphatase type 2A (PP2A). Our study shows that
      PPP2R2C is downregulated in glioma cells and human brain cancer patient samples.
      Overexpression of PPP2R2C inhibited cancer cell proliferation both in vitro and
      in vivo through the suppression of the activity of S6K in the mTOR pathway.
      Moreover, exogenous expression of PPP2R2C promoted the formation of a complex
      with the PP2A-C subunit to further enhance the binding of PP2A-C with S6K. Our
      results suggest that PPP2R2C is a potential tumor suppressor gene in human brain
      cancers. This study will provide novel insight into the development of
      therapeutic strategies in the treatment of human brain tumors.

PMID- 24126062
TI  - An ethnobotanical study of medicinal plants used by the local people of Alasehir
      (Manisa) in Turkey.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper represents the first large-scale
      ethnobotanical study in the Alasehir and its surrounding (Manisa/Turkey). There
      are scarcely any studies for using plants. There is urgency in recording such
      data. This is the first ethnobotanical study in which statistical calculations
      about plants are done by ICF (Informant Consensus Factor) method. This study
      aimed to identify plants collected for medicinal purposes by the local people of
      Alasehir, located in the Aegean Region of Turkey, and to document the traditional
      names, preparation and uses of these plants. MATERIALS AND METHODS: Field study
      was carried out over a period of approximately 2 years (2010-2012) in Alasehir.
      During this period, 137 vascular plant specimens were collected. Demographic
      characteristics of participants, local plant names, utilized parts and
      preparation methods of the plants were investigated and recorded. In the scope of
      the study, medicinal plant species and related information were collected;
      herbarium materials were prepared; and the specimens were entitled. Field
      research was conducted by collecting ethnobotanical information during structured
      and semi-structured interviews with native knowledgeable people in territory. In
      addition, the relative importance value of species was determined and ICF was
      calculated for the medicinal plants included in the study. RESULTS: A total of
      137 medicinal plants belonging to 58 families were identified in the region.
      Among them, 105 species are wild and 32 species are cultivated plant. The most
      dominant medicinal plant families were Asteraceae (>13%), Lamiaceae (>11%),
      Rosaceae (>7%), and Fabaceae (>4%), again; the most common preparations were
      infusion and decoction. It was found that Origanum onites L., Urtica urens,
      Thymus zygioides Griseb., Matricaria chamomilla L., Salvia tomentosa Mill.,
      Cerasus avium (L.), Tilia argentea Desf. ex DC., Hyoscyamus niger L., Urtica
      pilulifera L., Anethum graveolens L., Euphorbia rigida Bieb., Hypericum
      perforatum L., Paliurus spina-christi Mill., Rosa canina L., Viscum album L.
      subsp. austriacum (Wiesb.) Vollman, Silybum marianum (L.) Gaertn., Elymus repens
      (L.) Gould and Juglans regia L. were the most commonly used species. The
      traditional medicinal plants have been mostly used for the treatment respiratory
      tract diseases (14.1%), gastro-intestinal diseases (10%), kidney problems (7.3%),
      diabetes (7.1%), cholesterol (5%), rheumatism (4%), cancer various (4%),
      cardiovascular problems (3.1%) and burn (3%). CONCLUSION: Gathering, processing
      and consuming wild edible plants are still practiced in all the studied Alasehir
      areas. These plants, used in the treatment of many different diseases, are freely
      harvested in this region at abundant amounts. Due to the increasing health
      service facilities in the area, herbal medicine, seemed to be more related to
      health care and disease prevention than cure.

PMID- 24126061
TI  - Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium
      intybus L.): a comparative in vitro study with the effects of caffeic and ferulic
      acids.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Eurasia folk medicine, roots of chicory
      (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In
      vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has
      been shown to increase insulin secretion by pancreatic beta-cells and glucose
      uptake by muscle cells. MATERIALS AND METHODS: In vitro experiments were designed
      to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids,
      to those obtained with NCRAE (50 and 100 ug.mL(-1)) on the three major tissues
      implicated in glycemic regulation (pancreas, muscle and liver). In vivo
      experiments were performed in Wistar rats submitted to a daily intraperitoneal
      injection of NCRAE (3, 15 or 30 mg kg(-1)) for 4 days. On the fourth day, an
      intraperitoneal glucose tolerance test (IPGTT; 1 g kg(-1)) was carried out.
      RESULTS: Our results show that the three compounds we used are able each to
      induce an original response. Caffeic acid mainly promotes a decrease in hepatic
      glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a
      reduction of hepatic glycogenolysis. However, this compound induces an inhibition
      of muscle glucose uptake. NCRAE provokes an increase of insulin release and
      glucose uptake without any effect on hepatic glycogenolysis. We could also show
      that none of these compounds implicates hepatic glucose 6-phosphatase in contrast
      to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is
      able to decrease glucose output from hepatocytes. Our results point out that
      NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in
      vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve
      IP glucose tolerance in a dose-dependent manner and mainly via an insulin
      sensitizing effect. CONCLUSIONS: We conclude that NCRAE presents an
      antihyperglycemic effect essentially due to a peripheral effect on muscle glucose
      uptake.

PMID- 24126063
TI  - Exercising away the blues: can it help multiple sclerosis-related depression?
AB  - The present review focuses on exercise as a treatment for depression in multiple
      sclerosis. While exercise has emerged as a potentially useful treatment in the
      general psychiatry-depression literature, the findings from a small number of
      multiple sclerosis-related treatment trials are equivocal. Methodological
      limitations, including the absence of depression as a primary endpoint,
      characterize all the studies completed to date. Given that limitations in study
      design can be rectified, it is time to put exercise to the test once more.
      Depressed multiple sclerosis patients and those involved in their care are
      looking for guidance here because the prevailing zeitgeist promotes the benefits
      of exercise to mood. But first, some clarity is needed. 

PMID- 24126064
TI  - Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing
      multiple sclerosis: a randomised, controlled phase 3 trial.
AB  - BACKGROUND: In previous studies, teriflunomide significantly reduced the
      annualised relapse rate (ARR) and disability progression. OBJECTIVE: This phase
      3, rater-blinded study (NCT00883337) compared teriflunomide with interferon-beta
      1a (IFNbeta-1a). METHODS: Patients with relapsing multiple sclerosis were
      randomised (1:1:1) to oral teriflunomide 7-or 14 mg, or subcutaneous IFNbeta-1a
      44 ug. The primary composite endpoint was time to failure, defined as first
      occurrence of confirmed relapse or permanent treatment discontinuation for any
      cause. Secondary endpoints included ARR, Fatigue Impact Scale (FIS) and Treatment
      Satisfaction Questionnaire for Medication (TSQM). The study was completed 48
      weeks after the last patient was randomised. RESULTS: Some 324 patients were
      randomised (IFNbeta-1a: 104; teriflunomide 7 mg: 109; teriflunomide 14 mg: 111).
      No difference in time to failure was observed. There was no difference in ARR
      between teriflunomide 14 mg and IFNbeta-1a, but ARR was significantly higher with
      teriflunomide 7 mg. FIS scores indicated more frequent fatigue with IFNbeta-1a,
      though differences were only significant with teriflunomide 7 mg. TSQM scores
      were significantly higher with teriflunomide. There were no unexpected safety
      findings. CONCLUSION: Effects on time to failure were comparable between
      teriflunomide and IFNbeta-1a. There was no difference between teriflunomide 14 mg
      and IFNbeta-1a on ARR, though ARR was higher with teriflunomide 7 mg. The
      teriflunomide safety profile was consistent with previous studies.

PMID- 24126065
TI  - Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis,
      downregulated by interferon treatment, and affected by season.
AB  - BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated disease of the central
      nervous system which responds to therapies targeting circulating immune cells.
      OBJECTIVE: Our aim was to test if the T-cell activation gene expression pattern
      (TCAGE) we had previously described from whole blood was replicated in an
      independent cohort. METHODS: We used RNA-seq to interrogate the whole blood
      transcriptomes of 72 individuals (40 healthy controls, 32 untreated MS). A cohort
      of 862 control individuals from the Brisbane Systems Genetics Study (BSGS) was
      used to assess heritability and seasonal expression. The effect of interferon
      beta (IFNB) therapy on expression was evaluated. RESULTS: The MS/TCAGE
      association was replicated and rationalized to a single marker, ribosomal protein
      S6 (RPS6). Expression of RPS6 was higher in MS than controls (p<0.0004), and
      lower in winter than summer (p<4.6E-06). The seasonal pattern correlated with
      monthly UV light index (R=0.82, p<0.002), and was also identified in the BSGS
      cohort (p<0.0016). Variation in expression of RPS6 was not strongly heritable.
      RPS6 expression was reduced by IFNB therapy. CONCLUSIONS: These data support
      investigation of RPS6 as a potential therapeutic target and candidate biomarker
      for measuring clinical response to IFNB and other MS therapies, and of MS disease
      heterogeneity.

PMID- 24126066
TI  - Racial differences in beliefs of physician prescribing practices for low-cost
      pharmacy options.
AB  - BACKGROUND: Previous studies have reported that certain populations are sensitive
      to high out-of-pocket drug costs, and drug noncompliance leads to poorer health
      outcomes. OBJECTIVE: Our aim was to measure patient awareness of discount
      pharmacy options, cost barriers to medication access, and beliefs about health
      care provider's use of low-cost medications. METHODS: This cross-sectional 17
      item survey was administered to patients in the emergency department of an urban
      trauma center in February 2011. Differences in responses by sex and race groups
      were assessed. A logistic regression model was created to estimate the
      association of sociodemographic factors and medication use with awareness of
      discount pharmacy options. RESULTS: Five hundred and fifty-two surveys were
      analyzed. Among respondents who were prescribed medications within the past year,
      three fourths of patients felt comfortable asking physicians for cheaper
      medicines. Slightly more than half were aware of low-cost pharmacy options, and
      78% of these respondents correctly listed at least one of these pharmacies.
      Caucasian patients were more comfortable than African American patients asking
      for cheaper medicines (82.5% vs. 72.2%; p < 0.05) and were more aware of low-cost
      prescription programs (63.9% vs. 43.5%; p < 0.001). When adjusted for insurance
      status and current medication use, Caucasian patients were 2.7 times more likely
      to name a valid discount pharmacy option compared to African Americans (95%
      confidence interval 1.85-4.07). CONCLUSIONS: This study suggests populations may
      be more uncomfortable initiating a discussion about medication costs and
      selection of lower-cost alternatives. Health care providers may need to develop
      communication strategies in which medication cost is addressed with sensitivity
      and consistency.

PMID- 24126067
TI  - Emergency biliary sonography: utility of common bile duct measurement in the
      diagnosis of cholecystitis and choledocholithiasis.
AB  - BACKGROUND: Measurement of the common bile duct (CBD) has traditionally been
      considered an integral part of gallbladder sonography, but accurate
      identification of the CBD can be difficult for novice sonographers. OBJECTIVE: To
      determine the prevalence of isolated sonographic CBD dilation in emergency
      department (ED) patients with cholecystitis or choledocholithiasis without
      laboratory abnormalities or other pathologic findings on biliary ultrasound.
      METHODS: We conducted a retrospective chart review on two separate ED patient
      cohorts between June 2000 and June 2010. The first cohort comprised all ED
      patients undergoing a biliary ultrasound and subsequent cholecystectomy for
      presumed cholecystitis. The second cohort consisted of all ED patients receiving
      a biliary ultrasound who were ultimately diagnosed with choledocholithiasis.
      Ultrasound data and contemporaneous laboratory values were collected.
      Postoperative gallbladder pathology reports and endoscopic retrograde
      cholangiopancreatography (ERCP) reports were used as the criterion standard for
      final diagnosis. RESULTS: Of 666 cases of cholecystitis, there were 251 (37.7%)
      with a dilated CBD > 6 mm and only 2 cases (0.3%; 95% confidence interval [CI]
      0.0-0.7%) of isolated CBD dilation with an otherwise negative ultrasound and
      normal laboratory values. Of 111 cases of choledocholithiasis, there were 80
      (72.0%) with a dilated CBD and only 1 case (0.9%; 95% CI 0.0-2.7%) with an
      otherwise negative ultrasound and normal laboratory values. CONCLUSION: The
      prevalence of isolated sonographic CBD dilation in cholecystitis and
      choledocholithiasis is <1%. Omission of CBD measurement is unlikely to result in
      missed cholecystitis or choledocholithiasis in the setting of a routine ED
      evaluation with an otherwise normal ultrasound and normal laboratory values.

PMID- 24126068
TI  - Cimex "liketolickus".

PMID- 24126069
TI  - Just another sore throat?

PMID- 24126070
TI  - Slow-onset and fast-onset symptom presentations in acute coronary syndrome (ACS):
      new perspectives on prehospital delay in patients with ACS.
AB  - BACKGROUND: Patient decision delay is the main reason why many patients fail to
      receive timely medical intervention for symptoms of acute coronary syndrome
      (ACS). STUDY OBJECTIVES: This study examines the validity of slow-onset and fast
      onset ACS presentations and their influence on ACS prehospital delay times. A
      fast-onset ACS presentation is characterized by sudden, continuous, and severe
      chest pain, and slow-onset ACS pertains to all other ACS presentations. METHODS:
      Baseline data pertaining to medical profiles, prehospital delay times, and ACS
      symptoms were recorded for all ACS patients who participated in a large multisite
      randomized control trial (RCT) in Dublin, Ireland. Patients were interviewed 2-4
      days after their ACS event, and data were gathered using the ACS Response to
      Symptom Index. RESULTS: Only baseline data from the RCT, N = 893 patients, were
      analyzed. A total of 65% (n = 577) of patients experienced slow-onset ACS
      presentation, whereas 35% (n = 316) experienced fast-onset ACS. Patients who
      experienced slow-onset ACS were significantly more likely to have longer
      prehospital delays than patients with fast-onset ACS (3.5 h vs. 2.0 h,
      respectively, t = -5.63, df 890, p < 0.001). A multivariate analysis of delay
      revealed that, in the presence of other known delay factors, the only independent
      predictors of delay were slow-onset and fast-onset ACS (beta = -.096, p < 0.002)
      and other factors associated with patient behavior. CONCLUSION: Slow-onset ACS
      and fast-onset ACS presentations are associated with distinct behavioral patterns
      that significantly influence prehospital time frames. As such, slow-onset ACS and
      fast-onset ACS are legitimate ACS presentation phenomena that should be seriously
      considered when examining the factors associated with prehospital delay.

PMID- 24126071
TI  - Refractory anti-laminin gamma1 pemphigoid with psoriasis vulgaris successfully
      treated by double-filtration plasmapheresis.

PMID- 24126072
TI  - In vitro growth and maturation of vitrified-warmed bovine oocytes collected from
      early antral follicles.
AB  - Cryopreservation of growing oocytes enriches the choice of timing and location of
      artificial embryo production. However, completion of oocyte growth after warming
      is crucial when using such cryopreserved oocytes. Our research objective was to
      develop a sequential system that incorporates cryopreservation of growing bovine
      oocytes and their subsequent in vitro growth. Oocyte-granulosa cell complexes
      with a mean oocyte diameter of approximately 100 um were vitrified-warmed and
      then cultured for 14 days. The percentage of surviving oocytes following
      cryopreservation and 14-day culture was approximately 80%. More than half of the
      surviving oocytes were capable of maturing to metaphase II after in vitro
      maturation; the rate was comparable to that of control oocytes grown in vitro
      without cryopreservation. Taken together, the combined protocols for
      vitrification-warming of growing oocytes and subsequent in vitro growth can
      produce oocytes capable of undergoing meiotic maturation. 

PMID- 24126073
TI  - Less is more: improving proteostasis by translation slow down.
AB  - Protein homeostasis, or proteostasis, refers to a proper balance between
      synthesis, maturation, and degradation of cellular proteins. A growing body of
      evidence suggests that the ribosome serves as a hub for co-translational folding,
      chaperone interaction, degradation, and stress response. Accordingly, in addition
      to the chaperone network and proteasome system, the ribosome has emerged as a
      major factor in protein homeostasis. Recent work revealed that high rates of
      elongation of translation negatively affect both the fidelity of translation and
      the co-translational folding of nascent polypeptides. Accordingly, by slowing
      down translation one can significantly improve protein folding. In this review,
      we discuss how to target translational processes to improve proteostasis and
      implications in treating protein misfolding diseases. 

PMID- 24126074
TI  - Off-target response of a Wip1 chemical inhibitor in skin keratinocytes.
AB  - BACKGROUND: The wild type p53 inducible phosphatase (Wip1) plays an important
      role in modulating not only stress responses by various environmental stresses,
      but when overexpressed it also impairs the intrinsic tumor surveillance networks
      that are frequently found in a number of cancers including skin cancers. As a
      result, using a pharmacological inhibitor of Wip1 has been suggested to be a
      novel chemotherapeutic approach to recover the innate tumor surveillance in a
      variety of cancers. OBJECTIVE: We studied the effect of a pharmacological
      inhibitor of Wip1 in skin keratinocytes, under a ultra-violet (UV) stress
      condition. METHODS: A human keratinocyte cell line or human epidermal
      keratinocytes were exposed to UV, with or without the sole commercially available
      chemical inhibitor of Wip1, CCT007093; subsequently, we determined the diverse
      stress responses, including apoptosis and the activation of stress signaling.
      RESULTS: We demonstrate that the Wip1 inhibitor unexpectedly attenuated the UV
      mediated apoptotic response in skin keratinocytes, as a consequence of attenuated
      JNK activation and reduced H2AX phosphorylation in both, skin keratinocytes and a
      Wip1-null cell model. On the other hand, the loss of Wip1 expression, either by
      knockout or knockdown in mice or human keratinocytes respectively, promoted
      apoptosis and potentiated H2AX phosphorylation following UV treatment. Of note,
      CCT007093 treatment appeared to promote apoptosis in breast cancer cells and skin
      transformed keratinocytes that ectopically expressed Wip1, demonstrating that the
      effect of CCT007093 differs based on the level of Wip1 expression. CONCLUSION:
      Thus, our studies suggest that the development of a more potent and specific Wip1
      inhibitor is necessary to achieve the desired chemotherapeutic potential and to
      avoid off-target effects.

PMID- 24126076
TI  - Revision rates and complication incidence in single- and multilevel anterior
      cervical discectomy and fusion procedures: an administrative database study.
AB  - BACKGROUND CONTEXT: The natural history of cervical degenerative disease with
      operative management has not been well described. Even with symptomatic and
      radiographic evidence of multilevel cervical disease, it is unclear whether
      single- or multilevel anterior cervical discectomy and fusion (ACDF) procedures
      produce superior long-term outcomes. PURPOSE: To describe national trends in
      revision rates, complications, and readmission for patients undergoing single and
      multilevel ACDF. STUDY DESIGN: Administrative database study. PATIENT SAMPLE:
      Between 2006 and 2010, 92,867 patients were recorded for ACDF procedures in the
      Thomson Reuters MarketScan database. Restricting to patients with >24 months
      follow-up, 28,777 patients fulfilled our inclusion criteria, of which 12,744
      (44%) underwent single-level and 16,033 (56%) underwent multilevel ACDFs. OUTCOME
      MEASURES: Revision rates and postoperative complications. METHODS: We used the
      MarketScan database from 2006 to 2010 to select ACDF procedures based on Current
      Procedural Terminology coding at inpatient visit. Outcome measures were
      ascertained using either International Classification of Disease version 9 or
      Current Procedural Terminology coding. RESULTS: Perioperative complications were
      more common in multilevel procedures (odds ratio [OR], 1.4; 95% confidence
      interval [CI], 1.2-1.6; p<.0001). Single-level ACDF patients had higher rates of
      postoperative cervical epidural steroid injections (OR, 0.88; 95% CI, 0.8-1.0;
      p=.01). Within 30 days after index procedure, the multilevel ACDF cohort was 1.6
      times more likely to have undergone revision (OR, 1.6; 95% CI, 1.1-2.4; p=.02).
      At 2 years follow-up, revision rates were 9.13% in the single-level ACDF cohort
      and 10.7% for multilevel ACDFs (OR, 1.2; 95% CI, 1.1-1.3; p<.0001). In a
      multivariate analysis at 2 years follow-up, patients from the multilevel cohort
      were more likely to have received a surgical revision (OR, 1.1; 95% CI, 1.0-1.2;
      p=.001), to be readmitted into the hospital for any cause (OR, 1.2; 95% CI, 1.1
      1.4; p=.007), and to have suffered complications (OR, 1.3; 95% CI, 1.1-1.5;
      p=.0003). CONCLUSIONS: In this study, we report rates of adverse events and the
      need for revision surgery in patients undergoing single versus multilevel ACDFs.
      Increasing number of levels fused at the time of index surgery correlated with
      increased rate of reoperations. Multilevel ACDF patients requiring additional
      surgery more often underwent more extensive revision surgeries.

PMID- 24126075
TI  - The pathogenesis of nephropathia epidemica: new knowledge and unanswered
      questions.
AB  - Puumala virus (PUUV) causes an acute hemorrhagic fever with renal syndrome
      (HFRS), a zoonosis also called nephropathia epidemica (NE). The reservoir host of
      PUUV is the bank vole (Myodes glareolus). Herein we review the main clinical
      manifestations of NE, acute kidney injury, increased vascular permeability,
      coagulation abnormalities as well as pulmonary, cardiac, central nervous system
      and ocular manifestations of the disease. Several biomarkers of disease severity
      have recently been discovered: interleukin-6, pentraxin-3, C-reactive protein,
      indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen
      activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular
      endothelial growth hormone, complement, bradykinin, cellular immune response and
      other mechanisms in the pathogenesis of NE as well as host genetic factors will
      be discussed. Finally therapeutic aspects and directions for further research
      will be handled. 

PMID- 24126077
TI  - Traumatic bilateral facet dislocation of lumbar spine: "double facet sign".

PMID- 24126078
TI  - Gating charge movement precedes ionic current activation in hERG channels.
AB  - We recently reported gating currents recorded from hERG channels expressed in
      mammalian TSA cells and assessed the kinetics at different voltages. We detected
      2 distinct components of charge movement with the bulk of the charge being
      carried by a slower component. Here we compare our findings in TSA cells with
      recordings made from oocytes using the Cut Open Vaseline Gap clamp (COVG) and go
      on to directly compare activation of gating charge and ionic currents at 0 and
      +60 mV. The data show that gating charge saturates and moves more rapidly than
      ionic current activates suggesting a transition downstream from the movement of
      the bulk of gating charge is rate limiting for channel opening.

PMID- 24126079
TI  - Research gaps in psoriasis: opportunities for future studies.
AB  - Over the past 2 decades, considerable progress has been made to further elucidate
      the complex pathogenesis of psoriasis, facilitating the development of a new
      armamentarium of more effective, targeted therapies. Despite these important
      advances, substantial deficits remain in our understanding of psoriasis and its
      treatment, necessitating further research in many areas. In the sixth section of
      the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in
      research and care were identified. We discuss the most important gaps in research
      that currently exist and make suggestions for studies that should be performed to
      address these deficits. These encompass both basic science and clinical research
      studies, including large, prospective epidemiologic studies to determine the true
      prevalence and natural history of psoriasis; further molecular studies in
      patients with psoriatic and psoriatic arthritis to understand the function of
      psoriasis susceptibility genes and to identify novel therapeutic targets; studies
      to examine the role of environmental factors in the development of psoriasis;
      further investigation of the relationship between psoriasis and cardiometabolic
      disease; studies that examine the role of adjunctive therapies such as
      psychological interventions in appropriate patient groups; and finally, studies
      to identify biomarkers of disease severity and treatment response to optimize
      patient therapy. 

PMID- 24126080
TI  - Walking tests during the exercise training: specific use for the cardiac
      rehabilitation.
AB  - Walk tests, principally the six-minute walk test (6mWT), constitute a safe,
      useful submaximal tool for exercise tolerance testing in cardiac rehabilitation
      (CR). The 6mWT result reflects functional status, walking autonomy and efficacy
      of CR on walking endurance, which is more pronounced in patients with low
      functional capacity (heart failure - cardiac surgery). The 6mWT result is a
      strong predictor of mortality. However, clinically significant changes and
      reliability are still subject to debate - probably because of the ambiguity in
      terms of the target speed (either comfortable or brisk walking). Of the other
      time-based walk tests, the 2-minute-walk test is the only one applicable during
      CR, reserved for patients with severe disabilities by its psychometric
      properties. Fixed-distance tests (principally the 200m fast walk test) and
      incremental shuttle walking, tests explore higher levels of effort and may
      represent a safe and inexpensive alternative to laboratory-based tests during CR.
      These walking tests may be useful for personalizing prescription of training
      programs. However, the minimum clinically significant difference has not yet been
      determined. Lastly, walking tests appear to be potential useful tools in
      promoting physical activity and behavioural changes at home. Thus, validation of
      other walk tests with better psychometric properties will be necessary. 

PMID- 24126081
TI  - Metabolic engineering of Arabidopsis for butanetriol production using bacterial
      genes.
AB  - 1,2,4-butanetriol (butanetriol) is a useful precursor for the synthesis of the
      energetic material butanetriol trinitrate and several pharmaceutical compounds.
      Bacterial synthesis of butanetriol from xylose or arabinose takes place in a
      pathway that requires four enzymes. To produce butanetriol in plants by
      expressing bacterial enzymes, we cloned native bacterial or codon optimized
      synthetic genes under different promoters into a binary vector and stably
      transformed Arabidopsis plants. Transgenic lines expressing introduced genes were
      analyzed for the production of butanetriol using gas chromatography coupled to
      mass spectrometry (GC-MS). Soil-grown transgenic plants expressing these genes
      produced up to 20 ug/g of butanetriol. To test if an exogenous supply of pentose
      sugar precursors would enhance the butanetriol level, transgenic plants were
      grown in a medium supplemented with either xylose or arabinose and the amount of
      butanetriol was quantified. Plants expressing synthetic genes in the arabinose
      pathway showed up to a forty-fold increase in butanetriol levels after arabinose
      was added to the medium. Transgenic plants expressing either bacterial or
      synthetic xylose pathways, or the arabinose pathway showed toxicity symptoms when
      xylose or arabinose was added to the medium, suggesting that a by-product in the
      pathway or butanetriol affected plant growth. Furthermore, the metabolite profile
      of plants expressing arabinose and xylose pathways was altered. Our results
      demonstrate that bacterial pathways that produce butanetriol can be engineered
      into plants to produce this chemical. This proof-of-concept study for
      phytoproduction of butanetriol paves the way to further manipulate metabolic
      pathways in plants to enhance the level of butanetriol production.

PMID- 24126082
TI  - Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides.
AB  - Ginsenosides are the primary bioactive components of ginseng, which is a popular
      medicinal herb and exhibits diverse pharmacological activities. Protopanaxadiol
      is the aglycon of several dammarane-type ginsenosides, which also has anticancer
      activity. For microbial production of protopanaxadiol, dammarenediol-II synthase
      and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH
      cytochrome P450 reductase gene of Arabidopsis thaliana, were introduced into
      Saccharomyces cerevisiae, resulting in production of 0.05 mg/g DCW
      protopanaxadiol. Increasing squalene and 2,3-oxidosqualene supplies through
      overexpressing truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, farnesyl
      diphosphate synthase, squalene synthase and 2,3-oxidosqualene synthase genes,
      together with increasing protopanaxadiol synthase activity through codon
      optimization, led to 262-fold increase of protopanaxadiol production. Finally,
      using two-phase extractive fermentation resulted in production of 8.40 mg/g DCW
      protopanaxadiol (1189 mg/L), together with 10.94 mg/g DCW dammarenediol-II (1548
      mg/L). The yeast strains engineered in this work can serve as the basis for
      creating an alternative way for production of ginsenosides in place of extraction
      from plant sources.

PMID- 24126083
TI  - Mediterranean diet habits in older individuals: associations with cognitive
      functioning and brain volumes.
AB  - To examine the association between dietary habits, cognitive functioning and
      brain volumes in older individuals, data from 194 cognitively healthy individuals
      who participated in the Prospective Investigation of the Vasculature in Uppsala
      Seniors cohort were used. At age 70, participants kept diaries of their food
      intake for 1week. These records were used to calculate a Mediterranean diet
      (MeDi) score (comprising dietary habits traditionally found in Mediterranean
      countries, e.g. high intake of fruits and low intake of meat), with higher scores
      indicating more pronounced MeDi-like dietary habits. Five years later,
      participants' cognitive capabilities were examined by the seven minute screening
      (7MS) (a cognitive test battery used by clinicians to screen for dementia), and
      their brain volumes were measured by volumetric magnetic resonance imaging.
      Multivariate linear regression analyses were constructed to examine the
      association between the total MeDi score and cognitive functioning and brain
      volumes. In addition, possible associations between MeDi's eight dietary features
      and cognitive functioning and brain volumes were investigated. From the eight
      dietary features included in the MeDi score, pertaining to a low consumption of
      meat and meat products was linked to a better performance on the 7MS test
      (P=0.001) and greater total brain volume (i.e. the sum of white and gray matter,
      P=0.03) when controlling for potential confounders (e.g. BMI) in the analysis.
      Integrating all dietary features into the total MeDi score explained less
      variance in cognitive functioning and brain volumes than its single dietary
      component meat intake. These observational findings suggest that keeping to a low
      meat intake could prove to be an impact-driven public health policy to support
      healthy cognitive aging, when confirmed by longitudinal studies. Further, they
      suggest that the MeDi score is a construct that may mask possible associations of
      single MeDi features with brain health domains in elderly populations. 

PMID- 24126084
TI  - Characterization of global gene expression during assurance of lifespan extension
      by caloric restriction in budding yeast.
AB  - Caloric restriction (CR) is the best-studied intervention known to delay aging
      and extend lifespan in evolutionarily distant organisms ranging from yeast to
      mammals in the laboratory. Although the effect of CR on lifespan extension has
      been investigated for nearly 80years, the molecular mechanisms of CR are still
      elusive. Consequently, it is important to understand the fundamental mechanisms
      of when and how lifespan is affected by CR. In this study, we first identified
      the time-windows during which CR assured cellular longevity by switching cells
      from culture media containing 2% or 0.5% glucose to water, which allows us to
      observe CR and non-calorically-restricted cells under the same conditions. We
      also constructed time-dependent gene expression profiles and selected 646 genes
      that showed significant changes and correlations with the lifespan-extending
      effect of CR. The positively correlated genes participated in transcriptional
      regulation, ribosomal RNA processing and nuclear genome stability, while the
      negatively correlated genes were involved in the regulation of several metabolic
      pathways, endoplasmic reticulum function, stress response and cell cycle
      progression. Furthermore, we discovered major upstream regulators of those
      significantly changed genes, including AZF1 (YOR113W), HSF1 (YGL073W) and XBP1
      (YIL101C). Deletions of two genes, AZF1 and XBP1 (HSF1 is essential and was thus
      not tested), were confirmed to lessen the lifespan extension mediated by CR. The
      absence of these genes in the tor1Delta and ras2Delta backgrounds did show non
      overlapping effects with regard to CLS, suggesting differences between the CR
      mechanism for Tor and Ras signaling. 

PMID- 24126085
TI  - Minocycline, often forgotten but preferred to trimethoprim-sulfamethoxazole or
      doxycycline for the treatment of community-acquired meticillin-resistant
      Staphylococcus aureus skin and soft-tissue infections.
AB  - Treatment of uncomplicated skin and soft-tissue abscesses caused by meticillin
      sensitive Staphylococcus aureus or meticillin-resistant S. aureus (MRSA) is
      problematic. Incision and drainage aside, oral antibiotic therapy for
      uncomplicated community-acquired MRSA (CA-MRSA) is limited and frequent choices
      include clindamycin, doxycycline or trimethoprim-sulfamethoxazole (TMP-SMX). The
      most common oral antibiotics used for CA-MRSA are doxycycline or TMP-SMX, which
      often fail to eradicate the infection. With MRSA, in vitro susceptibilities do
      not always predict in vivo effectiveness. In situations where doxycycline or TMP
      SMX fails in the treatment of uncomplicated cutaneous abscesses due to CA-MRSA,
      minocycline is reliably effective. 

PMID- 24126086
TI  - First report of Enterocytozoon bieneusi from dairy cattle in Argentina.
AB  - Fecal specimens were obtained from a total of 70 dairy calves less than two
      months old on 11 municipalities in Buenos Aires, Argentina. After removal of
      fecal debris by sieving and sucrose flotation, specimens were subjected to PCR to
      detect the presence of Enterocytozoon bieneusi. PCR revealed a 14.3% of
      prevalence for E. bieneusi with 10 positive calves from 7 municipalities. Gene
      sequence analysis conducted in all samples positives by PCR revealed the presence
      of six genotypes; four previously reported in cattle as well as humans (D, I, J,
      and BEB4), one never reported in cattle before but previously reported in humans
      (EbpC), and one novel genotype (BEB10). These results constitute the first
      molecular characterization of E. bieneusi in Argentina, and suggest a potential
      risk of zoonotic transmission in this area. 

PMID- 24126087
TI  - Parasite population dynamics in pigs infected with Trichuris suis and
      Oesophagostomum dentatum.
AB  - The aim of the present study was to investigate the population dynamics and
      potential interactions between Trichuris suis and Oesophagostomum dentatum in
      experimentally co-infected pigs, by quantification of parasite parameters such as
      egg excretion, worm recovery and worm location. Forty-eight helminth naive pigs
      were allocated into four groups. Group O was inoculated with 20 O. dentatum
      L3/kg/day and Group T with 10 T. suis eggs/kg/day. Group OT was inoculated with
      both 20 O. dentatum L3/kg/day and 10 T. suis eggs/kg/day, while Group C was kept
      as an uninfected control group. All inoculations were trickle infections
      administered twice weekly and were continued until slaughter. Faecal samples were
      collected from the rectum of all pigs at day 0, and twice weekly from 2 to 9
      weeks post first infection (wpi). Six pigs from each group were necropsied 5 wpi
      and the remaining 6 pigs from each group were necropsied 10 wpi. The faecal egg
      counts (FEC) and total worm burdens of O. dentatum were dramatically influenced
      by the presence of T. suis, with significantly lower mean FECs and worm burdens
      at 5 and 10 wpi compared to single infected pigs. Furthermore, in the presence of
      T. suis we found that O. dentatum was located more posteriorly in the gut. The
      changes in the Trichuris population were less prominent, but faecal egg counts,
      worm counts 5 wpi (57% recovered vs. 39%) and the proportion of infected animals
      at 10 wpi were higher in Group OT compared to Group T. The location of T. suis
      was unaffected by the presence of O. dentatum. These results indicate an
      antagonistic interaction between T. suis and O. dentatum which is dominated by T.
      suis.

PMID- 24126088
TI  - Effect of molecular weight and concentration of legume condensed tannins on in
      vitro larval migration inhibition of Haemonchus contortus.
AB  - The effect of molecular weight of condensed tannins (CT) from a variety of warm
      season perennial legumes commonly consumed by sheep and goats on anthelmintic
      activity has not been previously explored. The objectives of this study were to
      determine if molecular weight of CT from warm-season perennial legumes could
      predict the biological activity of CT relative to anthelmintic activity against
      ivermectin resistant L3 stage Haemonchus contortus (HC) using a larval migration
      inhibition (LMI) assay. A second objective was to determine if CT from warm
      season perennial legumes possess anthelmintic properties against L3 stage (HC).
      Lespedeza stuevei had the greatest concentration of total condensed tannin (TCT;
      11.7%), whereas, with the exception of Arachis glabrata, a CT-free negative
      control, Leucaena retusa had the least TCT (3.3%). Weight-average molecular
      weight of CT ranged from 552 Da for L. stuevei to 1483 Da for Lespedeza cuneata.
      The treatments demonstrating the greatest percent LMI were L. retusa, L. stuevei
      and Acacia angustissima var. hirta (65.4%, 63.1% and 42.2%, respectively). The
      ivermectin treatment had the smallest percent LMI (12.5%) against ivermectin
      resistant L3 HC. There was a weak correlation (R(2)=0.34; P=0.05) between CT MW
      and percent LMI, suggesting that molecular weight of CT is a weak contributing
      factor to CT biological activity as it relates to LMI of L3 stage HC. L. stuevei,
      L. retusa and A. angustissima var. hirta STP5 warrant further evaluation of
      anthelmintic properties in vivo.

PMID- 24126089
TI  - Generalized Taenia crassiceps cysticercosis in a chinchilla (Chinchilla
      lanigera).
AB  - Taenia crassiceps is a cestode parasite that uses carnivores as definitive hosts
      and rodents and rabbits as main intermediate hosts, but other animal species and
      humans may also get infected. One adult male chinchilla (Chinchilla lanigera)
      from an animal shelter in Switzerland presented widespread subcutaneous fluctuant
      swellings extended over the forehead, nose, face and thoracic regions with a
      progressive growth over 3 months. The thoracic swelling was surgically resected,
      and it consisted of numerous 3-4mm small transparent vesicles, mainly confined to
      the subcutaneous tissue, which were morphologically identified as cysticerci of
      T. crassiceps. The diagnosis was confirmed by PCR and DNA sequence analysis of
      fragments of the mitochondrial small subunit rRNA and NADH dehydrogenase subunit
      1 genes. After 1.5 months, due to enlargement of the swollen areas and
      deterioration of the general health condition, the chinchilla was euthanized and
      a necropsy was performed. Thousands of small cysticerci were observed widespread
      in the subcutis, involving underlying musculature of the whole body, in the
      thoracic cavity, larynx, pharynx and in the retropharyngeal region. Additionally,
      three larger metacestodes were detected in the liver and morphologically and
      molecularly identified as Taenia taeniaeformis strobilocerci. The present case
      represents an indicator of the environmental contamination with Taenia eggs,
      highlighting the risk of infection for susceptible animals and humans. Besides
      the clinical relevance for pets, T. crassiceps is a zoonotic parasite and can be
      also cause of severe cysticercosis in humans. 

PMID- 24126090
TI  - Detection of benzimidazole resistance in gastrointestinal nematodes of sheep and
      goats of sub-Himalyan region of northern India using different tests.
AB  - The present investigation was planned with the objective of studying the status
      of benzimidazole (BZ) resistance in gastrointestinal nematodes (GIN) of sheep and
      goats of different agro-climatic zones of sub-Himalyan region of northern India
      using in vivo faecal egg count reduction test (FECRT) and in vitro tests namely
      egg hatch assay (EHA) and larval development assay (LDA). Out of fourteen flocks,
      FECRT detected resistance in eight flocks (two sheep flocks and six goat flocks)
      with FECR% ranging from 54.95 to 90.86. Pre treatment coproculture contained
      predominantly Haemonchus contortus, followed by Trichostrongylus spp.,
      Oesophagostomum and Strongyloides, while post treatment coproculture results
      showed that only H. contortus survived fenbendazole (FBZ) (in FECRT) or
      thiabendazole (TBZ) (in LDA) treatment except in three flocks of Tarai region
      {one sheep flock (Us1), and two goat flocks (Ug1 and Ug5)} where BZ resistant
      Trichostrongylus were also detected. The GIN of those eight farms which were
      found resistant by FECRT were also detected resistant by EHA. Arithmetic mean and
      range of ED50 value of susceptible group was found to be 0.059 MUg/ml and 0.037
      0.096 MUg/ml, respectively, and the same for the resistant group were found to be
      0.119 MUg/ml and 0.101-0.147 MUg/ml, respectively. With LDA, the arithmetic mean
      and range of LC50 value of susceptible group was found 0.0030 MUg/ml and 0.001
      0.005 MUg/ml, respectively, and those of resistant group was found 0.0105 MUg/ml
      and 0.009-0.012 MUg/ml, respectively. The values of Spearman rank correlation
      coefficient indicated that negative correlation was found between FECR% and ED50
      and between FECR% and LC50 while positive correlation existed between ED50 and
      LC50 value and the p-values indicated that these correlations were statistically
      highly significant. In the present study, FECRT and EHA gave comparable results
      with regard to detection of BZ resistance in GIN in sheep and goats. Although
      with LDA, the threshold LC50 value could not be established as for EHA but LDA
      indicated the presence of low level of resistance in GIN of both sheep and goats.
      For effective worm control, regular monitoring for anthelmintic resistance is
      important to know the status of anthelmintic efficacy in a particular agro
      climatic zone. The baseline information thus generated will enable timely
      management of benzimidazoles resistance in GIN.

PMID- 24126091
TI  - Documentation of reproductive health counseling and contraception in women with
      inflammatory bowel diseases.
AB  - OBJECTIVE: Inflammatory bowel diseases (IBD) are commonly diagnosed during
      women's reproductive years. Counseling is important to avoid unintended pregnancy
      in a disease-poor state. We sought to determine reproductive counseling
      documentation by gastroenterologists in women with IBD. METHODS: An electronic
      query identified women, age 18-45, with IBD in an academic gastroenterology
      practice from 2010 to 2012. A random sample (15%) chart review determined
      contraception documentation and content/frequency of reproductive counseling.
      RESULTS: 100 patients were analyzed. Median age was 35 (range 19-45), 53% were
      married, and 69% had Crohn's disease. Median time since IBD diagnosis was 9 years
      (range 1-32) with a 5 visit median (range 1-45) over 31 months (range 1-105). A
      contraceptive method was identified in 24% of all patients. Nineteen patients
      (19%) had documentation of reproductive counseling. Only 1/100 patients had a
      specific reference to using contraception to avoid pregnancy. The remaining
      counseling included (1) medication effects on pregnancy, (2) disease control
      before pregnancy, or (3) mode of delivery planning. CONCLUSIONS: Outside of
      listing contraception as a "current medication", documentation of reproductive
      counseling at gastroenterology visits for IBD is sparse. PRACTICE IMPLICATIONS:
      In light of the importance of reproductive planning for women with IBD, future
      research on incentives and barriers to counseling is warranted.

PMID- 24126092
TI  - The influence of a professional physician network on clinical decision making.
AB  - OBJECTIVE: The aim of this study was to examine the role of physicians'
      professional networks in decision-making processes. METHODS: A professional
      network was examined in three stages: content analysis and categorization of
      discussions concerning decision-making processes, in-depth interviews, and a
      questionnaire. RESULTS: The RAMBAM network has professional as well as social
      roles. On a professional level, physicians seek approval of their initial line of
      reasoning regarding their clinical cases, but will consider other approaches if
      such are suggested by persons of professional repute or if answers are based on
      evidence-based medicine and include referral to a relevant source. On a social
      level, physicians want to be part of their professional community and share
      information and experiences. CONCLUSION: Physicians' professional networks have a
      social role that is expressed by a feeling of belonging to a community, as well
      as a professional role of capturing and disseminating medical knowledge during
      physicians' decision-making processes. Professional networks constitute a unique
      source of tacit knowledge that extends existing formal knowledge resources.
      PRACTICE IMPLICATIONS: The study can increase physicians' awareness of
      professional networks as a unique source of tacit knowledge and can assist in the
      future design of medical professional networks as knowledge resources for medical
      decision making.

PMID- 24126093
TI  - Design and evaluation of xanthine based adenosine receptor antagonists: potential
      hypoxia targeted immunotherapies.
AB  - Molecular modeling techniques were applied to the design, synthesis and
      optimization of a new series of xanthine based adenosine A(2A) receptor
      antagonists. The optimized lead compound was converted to a PEG derivative and a
      functional in vitro bioassay used to confirm efficacy. Additionally, the
      PEGylated version showed enhanced aqueous solubility and was inert to
      photoisomerization, a known limitation of existing antagonists of this class.

PMID- 24126094
TI  - Synthesis and antimicrobial profile of N-substituted imidazolium oximes and their
      monoquaternary salts against multidrug resistant bacteria.
AB  - Two different series of N-substituted imidazolium oximes and their monoquaternary
      salts were synthesized and biologically tested with respect to their ability to
      inhibit growth a diverse panel of antibiotic susceptible Gram-positive and
      antibiotic resistant Gram-negative bacteria as well fungal strains. The newly
      synthesized compounds were analyzed by spectral studies to confirm their
      structure. The preliminary results showed that all compounds tested possess
      promising antimicrobial potential against both susceptible Gram-positive and
      antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC
      values from 0.14 to 100.0 MUg/mL. The structure-activity relationship
      demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary
      salts 6 and 7 attached directly to the imidazolium ring could be essential for
      observed remarkable inhibitory profiles against clinically important pathogens
      Pseudomonas aeruginosa (MIC=0.14 MUg/mL) and Klebsiella pneumoniae (MIC=1.56
      MUg/mL). Furthermore, the broth microdilution assay was then used to investigate
      the antiresistance efficacy of compound 7 against fourteen extended-spectrum beta
      lactamase (ESBL)-producing strains in comparison to eight clinically relevant
      antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging
      between 0.39 and 12.50 MUg/mL against all of ESBL-producing strains, which leads
      to the suggestion that may be interesting candidate for development of new
      antimicrobials to combat multidrug resistant Gram-negative bacteria.

PMID- 24126095
TI  - Synthesis, structure elucidation and in vitro anticancer activities of novel
      derivatives of diethyl (2E)-2-[(2E)-(1-arylimidazolidin-2
      ylidene)hydrazono]succinate and ethyl (4-oxo-8-aryl-4,6,7,8-tetrahydroimidazo[2,1
      c][1,2,4]triazin-3-yl)acetate.
AB  - The worked out and optimized synthesis routes and remarkable antitumour
      activities in vitro of novel polynitrogenated derivatives of diethyl (2E)-2-[(2E)
      (1-arylimidazolidin-2-ylidene)hydrazono]succinate (7-10) and ethyl (4-oxo-8-aryl
      4,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetate (11-16) are
      presented. Small molecules based on the privileged 7,8-dihydroimidazo[2,1
      c][1,2,4]triazin-4(6H)-one scaffold (11-16) were obtained with fairly modest to
      good overall yields by very facile addition reactions of the nucleophilic centred
      1-aryl-2-hydrazonoimidazolidine hydroiodides to diethyl acetylenedicarboxylate
      (DEAD) in the presence of triethylamine (TEA) and a subsequent cyclocondensation
      of the putative intermediate chain hydrazones. Heterobicyclic products 12 and 14
      16 could also be prepared in high overall yields by an effective intramolecular
      cyclocondensation of the isolated stable and antiproliferative active
      heterocyclic hydrazones, namely, diethyl (2E)-2-[(2E)-(1-arylimidazolidin-2
      ylidene)hydrazono]succinates (7-10), performed in refluxing DMF. These
      intermediates are the first products to be formed in the result of an addition of
      the nucleophilic reactants, namely, 1-aryl-2-hydrazonoimidazolidines of the 1-6
      type, bearing the basic nitrogen atom of the hydrazono moiety (N-NH2), to the
      carbon-carbon triple bond of the highly electrophilic alkyne, that is, DEAD.
      Molecular structures of the synthesized compounds (7-16) in the DMSO-d6 solutions
      were verified by (1)H NMR and (13)C NMR spectral data. These were finally
      confirmed based on the advanced 2D HMBC and HMQC NMR experiments, which were
      performed for the two representatives (8 and 11) of the two synthesized sets of
      the bioactive substances. Among the majority of antiproliferative active
      molecules, the disclosed herein ethyl [4-oxo-8-(3-chlorophenyl)-4,6,7,8
      tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl]acetate (14) is proposed as a
      promising lead structure for the design of novel highly selective antitumour
      agents because of the distinctly marked lower cytotoxicity towards the primary
      cell line of normal HSF cells and several-fold higher against cancer cells used.
      A double fluorochrome mix-staining was performed in order to find out about the
      possible mode of action by which this novel small heterobicycle reveals
      remarkable antiproliferative effects in vitro. Taking into account the obtained
      double staining results, this small molecule was identified as capable of
      inducing significantly higher levels of necrotic cells in human cancer cell lines
      (T47D and HeLa) than in normal HSF cells. Furthermore, its cytotoxicity against
      cells was found to be connected to the predominant induction of necrosis over
      apoptosis. 

PMID- 24126096
TI  - Limited risks of major congenital anomalies in children of mothers with IBD and
      effects of medications.
AB  - BACKGROUND & AIMS: Concerns persist about the risk of major congenital anomalies
      in children of women with inflammatory bowel disease (IBD), and whether
      medication use affects risk. We assessed these risks, and variations in use of
      medications by women with IBD before, during, and after pregnancy. METHODS: We
      accessed data on children born to women 15-45 y old from 1990 through 2010, using
      a mother-child linked dataset from an electronic database of primary care records
      containing medical diagnoses, events, and drug prescriptions from across the
      United Kingdom. We identified pregnant women with IBD, and all prescriptions for
      5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were
      extracted from their primary care records. We calculated risks of major
      congenital anomaly in children of mothers with and without IBD, and in children
      exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or
      corticosteroids during their first trimester of fetal development. Logistic
      regression with a generalized estimating equation was used to provide risk
      estimates adjusted for confounders. We calculated proportions of women taking
      medications before, during, and after pregnancy and assessed whether cessation
      was associated with subsequent disease flares. RESULTS: Risks of a major
      congenital anomaly in 1703 children of mothers with IBD and 384,811 children of
      mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an
      adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In
      children of women with IBD, the adjusted odds ratios of a major congenital
      anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5
      aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI,
      0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or
      genital anomalies were found in children of women with IBD; 31.2% of women
      discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6
      mercaptopurine in early pregnancy. The risk of flares later in pregnancy was not
      related to cessation of medication. CONCLUSIONS: We found no evidence that IBD
      during pregnancy or medical therapy for IBD during pregnancy increases the risk
      of a major congenital anomaly in children. Patients should receive appropriate
      guidance on use of medication before and during pregnancy.

PMID- 24126098
TI  - Role of NRSF/REST in the regulation of cardiac gene expression and function.
AB  - Alterations in the cardiac gene program affect both cardiac structure and
      function, and play a key role in the progression of pathological cardiac
      remodeling and heart failure. For instance, reactivation of fetal cardiac genes
      in adults is a consistent feature of cardiac hypertrophy and heart failure.
      Investigation of the transcriptional regulation of cardiac genes revealed a
      transcriptional repressor, neuron-restrictive silencer factor (NRSF), also called
      repressor element-1 silencing factor (REST), to be an important regulator of
      multiple fetal cardiac genes. Inhibition of NRSF in the heart leads to cardiac
      dysfunction and sudden arrhythmic death accompanied by re-expression of various
      fetal genes, including those encoding fetal ion channels, such as the HCN
      channels and T-type Ca(2+) channels. These findings shed light on the crucial
      regulatory function of NRSF in the heart and its importance for maintaining
      normal cardiac integrity.

PMID- 24126097
TI  - Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV
      infection and cirrhosis, allowing for effective antiviral therapy.
AB  - BACKGROUND & AIMS: Thrombocytopenia is common among patients with hepatitis C
      virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and
      dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3
      randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon
      Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease
      (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the
      number of platelets in patients, thereby allowing them to receive initiation or
      maintenance therapy with PEG and RBV. METHODS: Patients with HCV infection and
      thrombocytopenia (platelet count <75,000/MUL) who participated in ENABLE-1 (n =
      715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries,
      received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients
      whose platelet counts reached the predefined minimal threshold for the initiation
      of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the
      antiviral treatment phase, and were assigned randomly (2:1) to groups that
      received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks,
      depending on HCV genotype). The primary end point was sustained virologic
      response (SVR) 24 weeks after completion of antiviral therapy. RESULTS: More
      patients who received eltrombopag than placebo achieved SVRs (ENABLE-1:
      eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo,
      13%; P = .0202). PEG was administered at higher doses, with fewer dose
      reductions, in the eltrombopag groups of each study compared with the placebo
      groups. More patients who received eltrombopag than placebo maintained platelet
      counts of 50,000/MUL or higher throughout antiviral treatment (ENABLE-1, 69% vs
      15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the
      exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%)
      and thromboembolic events, which were more common in the eltrombopag group of
      ENABLE-2. CONCLUSIONS: Eltrombopag increases platelet numbers in thrombocytopenic
      patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise
      ineligible or marginal patients to begin and maintain antiviral therapy, leading
      to significantly increased rates of SVR. Clinical trial no: NCT00516321,
      NCT00529568.

PMID- 24126099
TI  - Impact of vitiligo on the health-related quality of life of 104 adult patients,
      using Dermatology Life Quality Index and stress score: first Egyptian report.

PMID- 24126100
TI  - Biomechanical and biochemical protective effect of low-level laser therapy for
      Achilles tendinitis.
AB  - For three decades, low level laser therapy (LLLT) has been used for treatment of
      tendinitis as well as other musculoskeletal diseases. Nevertheless, the
      biological mechanisms involved remain not completely understood. In this work,
      the effects of LLLT and of the widely used nonsteroidal anti-inflammatory drug,
      diclofenac, have been compared in the case of collagenase-induced Achilles
      tendinitis. Wistar rats were treated with diclofenac or laser therapy. The
      tensile behavior of tendons was characterized through successive loading
      unloading sequences. The method considered 11 characteristic parameters to
      describe the mechanical behavior. It was shown that during the acute inflammatory
      process of the tendon, the mechanical properties were significantly correlated to
      the high levels of MMP-3, MMP-9 and MMP-13 expression presented in a previous
      paper (Marcos, R.L., et al., 2012). The treatment by non-steroidal anti
      inflammatory drugs such as diclofenac sodium produces a low protective effect and
      can affect the short-term biochemical and biomechanical properties. On the
      contrary, it is shown that LLLT exhibits the best results in terms of MMPs
      reduction and mechanical properties recovery. Thus, LLLT looks to be a promising
      and consistent treatment for tendinopathies. 

PMID- 24126101
TI  - Fracture patterns of the growth plate and surrounding bone in the ovine knee
      joint at different ages.
AB  - Fractures of the growth plate region were performed with cadaver specimens
      obtained from the ovine distal femur and proximal tibia. Specimens of 6 different
      ages, ranging from 1 week to 4 years, were investigated in order to determine
      changes in the fracture characteristics. Mechanical properties (crack resistance
      and notch tensile strength), supported by microscopy of the distal tibia
      (thickness of growth plate and its zones, trabecular bone volume ratio) were
      determined. The crack propagated through different regions depending on age,
      which was observed both in microscopy and mechanical tests. In specimens of
      younger animals the fracture typically went through trabecular bone, often
      parallel to the growth plate, and only sometimes through the growth plate
      cartilage. Specimens of older animals fractured directly through the growth plate
      cartilage, while trabecular bone was not affected at all. Adult specimens had
      significantly higher mechanical values than the young ones. The results reveal
      the underlying mechanical properties that induce different fracture patterns of
      the epiphyseal growth plate at different stages of growth. The possibility of
      fractures through trabecular bone parallel to the growth plate in newborns and
      infants should be considered when clinical radiographs of paediatric fractures
      are analysed and classified. 

PMID- 24126102
TI  - Whole prostate D90 and V100: a dose-response analysis of 2000 consecutive (125)I
      monotherapy patients.
AB  - PURPOSE: To examine the relationship between whole prostate dose metrics and
      disease-free survival (DFS) after (125)I low-dose-rate prostate brachytherapy
      (LDR-PB). METHODS AND MATERIALS: Data for the first 2000 LDR-PB monotherapy
      implants were extracted from a database containing patient, tumor, dosimetric,
      and outcomes information. By National Comprehensive Cancer Network criteria, half
      (n = 1006) had low-risk disease and half (n = 990) had intermediate-risk disease
      (four had high-risk disease). Most patients (58.4%) and 75.3% of intermediate
      risk patients received 3 months neoadjuvant and 3 months concomitant androgen
      deprivation therapy (ADT). Univariate and multivariate analyses were conducted
      using recognized prognostic factors and the whole prostate dose metrics D90 (the
      minimum dose received by 90% of the postimplant CT-based prostate volume) and
      V100 (the percent of the postimplant CT-based prostate volume that received at
      least 100% of the prescription dose). RESULTS: The median followup is 5 years
      (maximum, 12.5 years); the 5-, 7-, and 10-year actuarial DFS estimates are 96.0%,
      94.4%, and 93.0%, respectively. Of the recognized prognostic factors, only
      pretreatment prostate-specific antigen (p = 0.012) and Gleason sum (p = 0.010)
      were predictive of DFS. When analyzed as continuous variables, dose metrics were
      not predictive of DFS. However, most nonsignificant trends favored higher doses,
      and D90 values <130 Gy were predictive of an increased risk of recurrence in the
      non-ADT subset (N = 833; log rank, p = 0.018). CONCLUSIONS: Although D90 values
      of <130 Gy were predictive of an increased risk of recurrence in the non-ADT
      subset, neither D90 nor V100, when used as continuous variables, was predictive
      of DFS when applied to the entire cohort or in the subset analysis. This
      observation informs us that dose metrics are not equivalent to oncologic end
      points and must be calibrated against DFS for each physician and each institution
      offering LDR-PB.

PMID- 24126103
TI  - Ammonium stress in Arabidopsis: signaling, genetic loci, and physiological
      targets.
AB  - Ammonium (NH4(+)) toxicity is a significant ecological and agricultural issue,
      and an important phenomenon in cell biology. As a result of increasing soil
      nitrogen input and atmospheric deposition, plants have to deal with unprecedented
      NH4(+) stress from sources below and above ground. In this review, we describe
      recent advances in elucidating the signaling pathways and identifying the main
      physiological targets and genetic loci involved in the effects of NH4(+) stress
      in the roots and shoots of Arabidopsis thaliana. We outline new experimental
      approaches that are being used to study NH4(+) toxicity in Arabidopsis and
      propose an integrated view of behavior and signaling in response to NH4(+) stress
      in the Arabidopsis system. 

PMID- 24126104
TI  - Chlamydia, cyanobiont, or host: who was on top in the menage a trois?
AB  - The endosymbiont hypothesis proposes that photosynthate from the cyanobiont was
      exported to the cytosol of the eukaryote host and polymerized from ADP-glucose
      into glycogen. Chlamydia-like pathogens are the second major source of foreign
      genes in Archaeplastida, suggesting that these obligate intracellular pathogens
      had a significant role during the establishment of endosymbiosis, likely through
      facilitating the metabolic integration between the endosymbiont and the
      eukaryotic host. In this opinion article, we propose that a hexose phosphate
      transporter of chlamydial origin was the first transporter responsible for
      exporting photosynthate out of the cyanobiont. This connection pre-dates the
      recruitment of the host-derived carbon translocators on the plastid inner
      membranes of green and red algae, land plants, and photosynthetic organisms of
      higher order endosymbiotic origin. 

PMID- 24126105
TI  - The involvement of the docking protein Gab1 in mitogenic signalling induced by
      EGF and HGF in rat hepatocytes.
AB  - Grb2-associated binder (Gab) family proteins are docking molecules that can
      interact with receptor tyrosine kinases (RTKs) and cytokine receptors and bind
      several downstream signalling proteins. Studies in several cell types have shown
      that Gab1 may have a role in signalling mediated by the two RTKs epidermal growth
      factor (EGF) receptor (EGFR) and Met, the receptor for hepatocyte growth factor
      (HGF), but the involvement of Gab1 in EGFR and Met signalling has not been
      directly compared in the same cell. We have studied mechanisms of activation and
      role in mitogenic signalling of Gab1 in response to EGF and HGF in cultured rat
      hepatocytes. Gab1, but not Gab2, was expressed in the hepatocytes and was
      phosphorylated upon stimulation with EGF or HGF. Depletion of Gab1, using siRNA,
      decreased the ERK and Akt activation, cyclin D1 expression, and DNA synthesis in
      response to both EGF and HGF. Studies of mechanisms of recruitment to the
      receptors showed that HGF induced co-precipitation of Gab1 and Met while EGF
      induced binding of Gab1 to Grb2 but not to EGFR. Gab1 activation in response to
      both EGF and HGF was dependent on PI3K. While EGF activated Gab1 and Shc equally,
      within the same concentration range, HGF very potently and almost exclusively
      activated Gab1, having only a minimal effect on Shc. Collectively, our results
      strongly suggest that although Gab1 interacts differently with EGFR and Met, it
      is involved in mitogenic signalling mediated by both these growth factor
      receptors in hepatocytes.

PMID- 24126106
TI  - Divalent regulation and intersubunit interactions of human connexin26 (Cx26)
      hemichannels.
AB  - Control of plasma membrane connexin hemichannel opening is indispensable, and is
      achieved by physiological extracellular divalent ion concentrations. Here, we
      explore the differences between regulation by Ca(2+) and Mg(2+) of human
      connexin26 (hCx26) hemichannels and the role of a specific interaction in
      regulation by Ca (2+). To effect hemichannel closure, the apparent affinity of
      Ca(2+) (0.33 mM) is higher than for Mg(2+) (1.8 mM). Hemichannel closure is
      accelerated by physiological Ca(2+) concentrations, but non-physiological
      concentrations of extracellular Mg(2+) are required for this effect. Our recent
      report provided evidence that extracellular Ca(2+) facilitates hCx26 hemichannel
      closing by disrupting a salt bridge interaction between positions D50 and K61
      that stabilizes the open state. New evidence from mutant cycle analysis indicates
      that D50 also interacts with Q48. We find that the D50-Q48 interaction
      contributes to stabilization of the open state, but that it is relatively
      insensitive to disruption by extracellular Ca(2+) compared with the D50-K61
      interaction.

PMID- 24126107
TI  - Retrospective investigation of the remaining teeth status of patients with
      implant-supported fixed partial dentures in unilateral free-end edentulism.
AB  - PURPOSE: This study aimed to compare the various complication-free rates and
      survival rates of remaining teeth among implant-supported fixed dentures (IFDs),
      removable partial dentures (RPDs) and no-restoration (NR) patients with
      unilateral free-end edentulism. MATERIAL AND METHODS: The study subjects were
      selected among those who received prosthodontic treatment at Okayama University
      Dental Hospital for their unilateral free-end edentulism (2 or 3 missing teeth).
      Thirty-three patients were included in the IFD group, 41 matched patients in the
      RPD group, and 10 patients who received RPDs but refused their use were regarded
      as NR group. The remaining dentition was classified into five subcategories in
      relation to the missing portion: adjacent teeth to the missing portion (AD),
      contralateral posterior dentition in the same jaw (CS) and in the opposite jaw
      (CO), ipsilateral opposing posterior dentition (IO), and anterior dentition (AN).
      Complications were defined as tooth extraction, periodontal lesions, periapical
      lesions or loss of retention of the prosthesis and were assessed by one examiner
      based on the hospital chart records. RESULTS: The cumulative complication-free
      rates in the remaining teeth were significantly different among each of the three
      groups (p<0.01), with a significantly lower incidence rate in the IFD group.
      Regarding the cumulative survival rate of the remaining teeth, there was a
      significant difference only between IFD and NR group (p=0.01), especially in the
      CO region (p=0.04). CONCLUSIONS: Stable posterior occlusal support obtained with
      IFD treatment for unilateral free-end edentulism may reduce the incidence of
      complications in the remaining teeth, by decreasing the adverse mechanical
      stress.

PMID- 24126108
TI  - The Society for Vascular Surgery Lower Extremity Threatened Limb Classification
      System: risk stratification based on wound, ischemia, and foot infection (WIfI).
AB  - Critical limb ischemia, first defined in 1982, was intended to delineate a
      subgroup of patients with a threatened lower extremity primarily because of
      chronic ischemia. It was the intent of the original authors that patients with
      diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems
      have been used to classify risk of amputation and likelihood of benefit from
      revascularization by subcategorizing patients into two groups: ischemic rest pain
      and tissue loss. Due to demographic shifts over the last 40 years, especially a
      dramatic rise in the incidence of diabetes mellitus and rapidly expanding
      techniques of revascularization, it has become increasingly difficult to perform
      meaningful outcomes analysis for patients with threatened limbs using these
      existing classification systems. Particularly in patients with diabetes, limb
      threat is part of a broad disease spectrum. Perfusion is only one determinant of
      outcome; wound extent and the presence and severity of infection also greatly
      impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower
      Extremity Guidelines Committee undertook the task of creating a new
      classification of the threatened lower extremity that reflects these important
      considerations. We term this new framework, the Society for Vascular Surgery
      Lower Extremity Threatened Limb Classification System. Risk stratification is
      based on three major factors that impact amputation risk and clinical management:
      Wound, Ischemia, and foot Infection (WIfI). The implementation of this
      classification system is intended to permit more meaningful analysis of outcomes
      for various forms of therapy in this challenging, but heterogeneous population.

PMID- 24126109
TI  - External morphology of the mouthparts of the whitebacked planthopper Sogatella
      furcifera (Hemiptera: Delphacidae), with special reference to the sensilla.
AB  - The whitebacked planthopper, Sogatella furcifera (Horvath), is a major pest of
      rice in Asia, with the adults and larvae sucking the phloem sap and affecting
      plant growth. The ultrastructural morphology of the mouthparts, with distribution
      of sensilla located on the maxillae and labium in adult S. furcifera was observed
      using scanning electron microscopy and illustrated, with a brief discussion of
      their taxonomic and putative functional significance. The gross mouthparts
      comprising an uppermost small cone-shaped labrum, a three-segmented labium with a
      deep longitudinal groove on the anterior side, and a stylet fascicle consisting
      of two mandibular and two maxillary stylets, are consistent with the conventional
      piercing-sucking type of mouth parts found in Hemiptera. The mandibles bear 5
      teeth on the external convex region on the distal extremity. Smooth maxillary
      stylets, interlocked to form a larger food canal and a smaller salivary canal,
      are asymmetrical only in the internal position of longitudinal carinae and
      grooves. Two dendritic canals are also found in each maxilla and one in each
      mandible. The cross-section of the stylet fascicle is oval. The labial tip is a
      rosette shape. Two types of sensilla trichoides, two types of uniporous peg
      sensilla, two pairs of sensilla basiconica and a pair of subapical labial sensory
      organs have been detected at different locations on the labium, specifically the
      labial tip is divided into dorsal paired sensory fields with 9 pairs of uniporous
      peg sensilla and 1 pairs of dome-shaped sensilla, and ventral paired sensory
      fields with 2 pairs of sensilla basiconica.

PMID- 24126110
TI  - Glucose regulates protein kinase CK2 in pancreatic beta-cells and its interaction
      with PDX-1.
AB  - The pancreatic duodenal homeodomain transcription factor PDX-1 plays a pivotal
      role in the development of the pancreas and the maintenance of glucose
      homeostasis by pancreatic beta-cells. Recently, we found that the highly
      conserved, ubiquitously expressed tetrameric Ser/Thr protein kinase CK2, which is
      formed by two catalytic subunits (alpha and/or alpha') and two non-catalytic
      subunits (beta), phosphorylates PDX-1. So far, only little is known about CK2 in
      pancreatic beta-cells and how this enzyme is regulated in these cells. In the
      present study, we found that (i) CK2 binds to PDX-1, (ii) the binding between CK2
      and PDX-1 is regulated by glucose, (iii) glucose modulates the subcellular
      localization of PDX-1 and CK2 and (iv) the kinase activity is also regulated by
      glucose. Our novel data indicate that CK2 is a co-factor of PDX-1 in response to
      glucose in pancreatic beta-cells. 

PMID- 24126111
TI  - Autonomous cure of damaged human intestinal epithelial cells by TLR2 and TLR4
      dependent production of IL-22 in response to Spirulina polysaccharides.
AB  - In order to analyze the damage of human epithelial cells, we used human quasi
      normal FPCK-1-1 cells derived from a colonic polyp in a patient with familial
      adenomatous polyposis as a monolayer, which is co-cultured with peptidoglycan
      (PGN)-stimulated THP-1 cells. Co-cultured FPCK-1-1 cells showed a decreased
      transepithelial electrical resistance (TER) and the lower level of claudin-2.
      When Spirulina complex polysaccharides were added one day before the start of the
      co-culture, there was no decrease of TER and claudin-2 (early phase damage). In
      contrast, when Spirulina complex polysaccharides were added to FPCK-1-1 cells
      after the level of TER had decreased, there was no recovery at the level of
      claudin-2, though the TER level recovered (late phase damage). The mucosa
      reconstitution is suggested to be involved in the recovery from the damaged
      status. Interestingly, autonomous recovery of FPCK-1-1 cells from both the early
      and late phase damage requires the production of IL-22, because anti-IL-22
      antibodies inhibited recovery in these cases. Antibodies against either TLR2 or
      TLR4 inhibited the production of IL-22 from FPCK-1-1 colon epithelial cells,
      suggesting that signals through TLR2 and TLR4 are necessary for autonomous
      recovery of FPCK-1-1 colon epithelial cells by producing IL-22. In conclusion, we
      have established a useful model for the study of intestinal damage and recovery
      using human colon epithelial cells and our data suggest that damage to human
      colon epithelial cells can, at least in part, be recovered by the autonomous
      production of IL-22 in response to Spirulina complex polysaccharides. 

PMID- 24126112
TI  - Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model
      of ovalbumin induced chronic asthma.
AB  - Montelukast, a leukotriene receptor antagonist, is used commercially as a
      maintenance treatment for asthma and to relieve allergic symptoms. In this study,
      we evaluated the protective effects of montelukast against the airway
      inflammation and fibrosis using a murine model of ovalbumin (OVA) induced chronic
      asthma. The animals received OVA challenge three times a week for 4 weeks.
      Montelukast (30 mg/kg) was administrated orally once a day for 4 weeks. The
      administration of montelukast caused a reduction in elevated interleukin (IL)-4,
      IL-13, eotaxin, immunoglobulin (Ig), inflammatory cell infiltration into the
      airways, and mucus production after repeated OVA challenges. To investigate the
      antifibrotic mechanism of montelukast, we examined the expression of profibrotic
      mediators, including vascular endothelial growth factor (VEGF), transforming
      growth factor (TGF)-beta1, and Smad3 proteins in the lung tissue using western
      blotting and immunohistochemistry. The administration of montelukast reduced the
      overexpression of profibrotic proteins in the lung tissue, which was confirmed by
      immnunohistochemistry. These results are consistent with a histopathological
      examination of lung tissue with Masson's trichrome stain. In conclusion, the
      administration of montelukast reduced airway inflammation and pulmonary fibrosis
      by reducing the release of Th2 cytokines and the expression of VEGF, TGF
      beta1/Smad3 in the lung tissue.

PMID- 24126113
TI  - Honey-induced macrophage stimulation: AP-1 and NF-kappaB activation and cytokine
      production are unrelated to LPS content of honey.
AB  - Honey is well known for its wound healing properties although the cellular and
      molecular mechanisms underlying honey-stimulated healing process are still poorly
      understood. The present study was intended to characterize the stimulation of Raw
      264.7 murine macrophages in response to thyme honey. Honey induces significant
      increase in PGE2 production, and overexpression of both COX-2 and TNF-alpha
      (p<0.001). This increase was concomitant with overexpression and activation of
      the AP-1 and NF-kappaB transcription factor subunits. The small LPS content of
      honey could not, by itself, account for the reported observations. These results
      suggest that other thyme honey components participate in the stimulation of
      cytokine production required for effective wound healing process. 

PMID- 24126114
TI  - Amentoflavone inhibits iNOS, COX-2 expression and modulates cytokine profile, NF
      kappaB signal transduction pathways in rats with ulcerative colitis.
AB  - Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative
      stress, leucocyte infiltration and upregulation of pro-inflammatory cytokines.
      The aim of the present study was to examine the effect of amentoflavone on a
      murine model of ulcerative colitis (UC). UC was induced by intracolonic injection
      of 3% acetic acid in male Wistar rats. amentoflavone (10 mg/kg.b.wt) or reference
      drug sulfasalazine (100 mg/kg.b.wt) was administrated intra-peritoneally for 5
      consecutive days before induction of colitis with acetic acid. Administration of
      amentoflavone was found to reduce the extent of inflammatory colonic injury. This
      was manifested by a decrease in the score of mucosal injury, by lowered colonic
      wet weight as well as vascular permeability and diminished lactate dehydrogenase
      (LDH) and myeloperoxidase (MPO) activity reflecting reduced leukocyte
      infiltration. Furthermore, the mucosal content of lipid peroxidation (LPO),
      glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO) activity
      confirms that amentoflavone could significantly inhibit colitis. The treatment
      also reduced significantly the colonic tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta) and IL-6 levels as well as the expression of
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) compared to
      colitis control group. The histopathological studies also confirm the foregoing
      findings. amentoflavone was also able to inhibit the activation and translocation
      of transcription factors, nuclear factor (NF)-kappaB subunits (p65/p50). These
      results suggest that amentoflavone exhibits protective effect in acetic acid
      induced ulcerative colitis which might be due to its modulation of oxidant/anti
      oxidant balance, down-regulation of productions and expressions of pro
      inflammatory cytokines, inflammatory mediators and inhibition of NF-kappaB signal
      transduction pathways.

PMID- 24126115
TI  - The role of TLR2/JNK/NF-kappaB pathway in amyloid beta peptide-induced
      inflammatory response in mouse NG108-15 neural cells.
AB  - The TLR2-mediated neuroinflammatory activation has been involved in the
      pathogenesis of Alzheimer's disease (AD) associated with amyloid beta(Abeta)
      deposition. In neuronal damage, JNK and NF-kappaB pathways contribute to TLR2
      dependent secretion of proinflammatory cytokines. However, the role of
      TLR2/JNK/NF-kappaB pathway on Abeta-induced inflammatory response in nerve cell
      damage remains unclear. In the present study, Abeta1-42 was used to induce mouse
      NG108-15 neural cell injury. The cell viability was detected by
      methylthiazolyldiphenyl-tetrazolium bromide (MTT). The levels of tumor necrosis
      factor (TNF)-alpha, monocyte chemoattractant protein(MCP)-1 and interleukin (IL)
      10 in culture supernatant were measured by ELISA. western blot analysis was
      performed to detect the expressions of JNK and p-65 NF-kappaB proteins.
      Immunofluorescence assay was also performed to examine the p-JNK and p-65 NF
      kappaB activation. As a result, Abeta1-42 incubation for 36 h inhibited
      remarkedly the cell viability of NG108-15, and increased significantly the levels
      of inflammatory cytokines TNF-alpha, MCP-1 and IL-10, as well as enhanced the
      expressions of JNK and p-65 NF-kappaB in western blot analysis and
      immunofluorescence assay. However, the pre-incubation with anti-TLR2 (OPN301, 1
      MUg/ml) or JNK inhibitor SP600125 (10 MUg/ml) prior to Abeta1-42 administration,
      these upregulation events were all reduced. These results suggested that the
      induction of Abeta1-42 on proinflammatory cytokine generation might be associated
      with TLR2-dependent JNK/NF-kappaB signal pathway, at least partially. Our
      findings indicated that blockade of TLR2/JNK/NF-kappaB pathway could be
      beneficial in the pathogenesis of AD.

PMID- 24126117
TI  - Does noninvasive ventilation have a role in chest trauma patients?

PMID- 24126116
TI  - Trends in use of antipsychotics in elderly patients with dementia: Impact of
      national safety warnings.
AB  - Based on evidence of an increased risk of death, drug agencies issued safety
      warnings about the use of second generation antipsychotics (SGAs) in the elderly
      with dementia. The French agency issued a warning in 2004. which was extended to
      all antipsychotics in 2008. Little is known about the impact of these warnings on
      use. We conducted a quasi-experimental study (interrupted time-series) in France,
      for 2003-2011, including subjects aged >=65 with dementia and subjects aged >=65
      without dementia in the EGB database (1/97th representative random sample of
      claims from the main Health Insurance scheme). Outcomes were monthly rates of use
      of antipsychotics (by class and agent) and of five comparison drug classes
      (antidepressants, benzodiazepines, dermatologicals, antidiabetics,
      antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings
      by linear segmented regression. In patients with dementia (n=7169), there was a
      40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The
      reduction began before 2004 and was unaffected by the warnings. Use of first
      generation antipsychotics declined over the period, while use of SGAs increased
      and leveled off from 2007. Use of the five comparison drug classes increased on
      the period. In subjects without dementia (n=91,942), rates of overall
      antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of
      the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%.
      Antipsychotic use decreased in the elderly between 2003 and 2011, especially in
      dementia. The timing of the decrease, however, did not coincide with safety
      warnings. 

PMID- 24126118
TI  - Possible involvement of oxido-nitrosative stress induced neuro-inflammatory
      cascade and monoaminergic pathway: underpinning the correlation between
      nociceptive and depressive behaviour in a rodent model.
AB  - BACKGROUND: Pain and depression are frequent co-morbid disorders. The prevalence
      rate of depression is several times higher in patients with chronic pain than in
      the general population but the mechanism underlying this association is unknown.
      A combination of interactions between neurotransmitters, neuropeptides, oxidative
      and nitrosative stress and cytokines are thought to take part in pathogenesis of
      pain as well as depression. Thus, the aim of the present study was two-fold,
      first to investigate the interplay between nociception and associated depression
      and second to investigate the protective potential of berberine against the
      reserpine-induced nociceptive and depressive behaviour and further to explore the
      role of oxidative-nitrosative stress mediated inflammatory cascade and apoptotic
      signalling pathway in this dyad. METHODS AND RESULTS: Nociception and associated
      depression were induced by administration of reserpine (1mg/kg subcutaneous
      daily) for three consecutive days. This behavioural deficit was integrated with
      decrease in the biogenic amine (dopamine, norepinephrine and serotonin) levels
      along with increased substance P concentration, oxidative-nitrosative stress,
      inflammatory cytokines, NF-kappabeta and caspase-3 levels in different brain
      regions (cortex and hippocampus) of the reserpinised rats. LIMITATION: More
      studies are still warranted in similar rodent models of pain and depression, so,
      that the present findings can be further substantiated to establish the clinical
      effectiveness of berberine in a subset of patients suffering from pain as well as
      depression. CONCLUSION: The findings from the current study suggested that
      reserpine-induced neurochemical alterations and dysregulation of oxidative
      nitrosative stress induced inflammatory cascade underlies the co-morbidity of
      nociceptive behaviour and associated depression in rats.

PMID- 24126119
TI  - [Study of morbidity in Libreville (Gabon) in 2008].
AB  - We studied population morbidity in three neighborhoods in Libreville (Gabon),
      selected to represent the city center, the areas bordering the suburbs, and the
      areas in between. We surveyed 601 households and found that at least one resident
      was ill in 35% of the households. Malaria remains the leading cause of morbidity
      in all three districts, followed by fevers and diarrhea. Thus, the causes of
      morbidity in the general population with Libreville in 2008 matched those of
      hospital morbidity at the national level, where malaria remains the leading cause
      of medical visits. 

PMID- 24126120
TI  - Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the
      colon.
AB  - In colon cancer, the biological significance of lymphatic tumour spread remains a
      matter of debate, which impacts on related questions such as the ideal extent of
      lymphadenectomy and the prognostic significance of lymph node counts. Several
      lines of evidence suggest that metastasis to locoregional nodes occurs early and
      is a stochastic, rather than a stepwise phenomenon, and in essence reflects the
      tumour-host-metastasis relationship. Not surprisingly, therefore, several
      clinical trials failed to identify a survival benefit from extensive
      lymphadenectomy compared to standard resection. The recently described complete
      mesocolic excision technique, which aims to improve survival by maximizing nodal
      clearance, should be subjected to a prospective randomized trial. There has been
      a fairly consistent and intriguing relation between nodal counts and survival in
      colon cancer. Therapeutic effects of more extensive removal of invaded nodes seem
      an unlikely explanation for the observed association. Similarly, several findings
      argue against stage migration as the only or even the most important explanation.
      The available literature shows an extensive array of factors confounding the
      nodal count-survival relationship, which are correlated to the patient's clinical
      characteristics, pathology variables, and factors relating to the individual
      (treating surgeon and pathologist) and institutional healthcare levels. More
      research into the biology of nodal spread and the nodal count-survival
      relationship is indicated and may have important implications for therapy such as
      the further introduction of minimally invasive surgery and the identification of
      novel and potentially modifiable factors impacting on both nodal counts and
      survival. 

PMID- 24126121
TI  - Time for more optimism in metastatic breast cancer?
AB  - Treatment of metastatic breast cancer has substantially changed in the last
      decades. Availability of new cytotoxics and targeted therapies as well as changes
      in treatment philosophy and strategy have all contributed to a significant
      improvement in both survival and patients' quality of life. The multidisciplinary
      approach, personalised treatments based on tumour characteristics, patient's and
      disease history, as well as re-definition of treatment goals, aiming at the
      lowest possible impact on patients' life by replacing aggressive multidrug
      chemotherapy with single-agent cytotoxic treatment or endocrine+/-targeted
      therapies, have all been the bases of the new treatment paradigm. More recently
      the development of the international advanced breast cancer (ABC) consensus
      guidelines have further contributed to this improvement. This review will focus
      on the major achievements and challenges in the different tumour subtypes and
      sites, with a focus on future research topics and trends.

PMID- 24126122
TI  - Hawthorn fruit attenuates atherosclerosis by improving the hypolipidemic and
      antioxidant activities in apolipoprotein e-deficient mice.
AB  - AIMS: The protective effects of hawthorn fruit against atherosclerosis and the
      potential underlying mechanisms of this fruit in improving the hypolipidemic and
      antioxidant activities were investigated in apolipoprotein E-deficient(apoE(-/-))
      mice. METHODS: ApoE(-/-) mice were divided into a control group(n=10) and
      hawthorn fruit group(n=10). The mean size of the lesions in the aortic root was
      assessed, and the serum glucose levels, insulin levels, lipid profiles, total
      antioxidant capacity(T-AOC) and superoxide dismutase(SOD) and glutathione
      peroxidase(GSH-PX) activities were measured. The mRNA levels of hepatic genes
      related to lipid metabolism and antioxidant enzymes were examined. RESULTS: The
      hawthorn fruit group mice developed significantly decreased(p<0.05)
      atherosclerotic lesions. The levels of serum lipids decreased
      significantly(p<0.05) and the levels of cholesterol/triglycerides, including very
      low-density lipoprotein(VLDL) and low-density lipoprotein(LDL), decreased in the
      hawthorn fruit group. The hawthorn fruit mice exhibited significantly increased T
      AOC values and SOD and GSH-PX activities(p<0.05). The hepatic fatty acid
      synthase(FAS) and sterol regulatory element binding protein-1c(SREBP-1c) mRNA
      levels were reduced by 42%(p<0.05) and 23% p<0.05) in the mice fed the hawthorn
      fruit diet compared with that observed in the mice fed a standard diet. However,
      the hepatic hydroxymethylglutaryl CoA reductase(HMG-CoAR) mRNA levels showed no
      significant differences between the two groups. The mRNA expression levels of the
      antioxidant enzymes(SOD1, SOD2, Gpx3) were higher(p<0.05) in the livers of the
      hawthorn fruit diet mice compared with those observed in the control mice.
      CONCLUSIONS: Hawthorn fruit exerts a protective effect against atherosclerosis in
      apoE(-/-) mice by improving the hypolipidemic and antioxidant activities.

PMID- 24126123
TI  - Flow-mediated vasodilation was found to be an independent predictor of changes in
      the carotid plaque status during a 5-year follow-up.
AB  - AIM: It has previously been shown that flow-mediated vasodilation is a predictor
      of the progression of the intima-media thickness (IMT). In the present study, the
      degree of endothelium-dependent vasodilation in both resistance and conduit
      arteries was evaluated as a predictor of the IMT and plaque progression. METHODS:
      In the population-based Prospective Study of the Vasculature in Uppsala
      Seniors(PIVUS) trial(1,016 subjects all 70 years of age), the invasive forearm
      technique using acetylcholine administered in the brachial artery (resistance
      artery, EDV) and the brachial artery ultrasound technique with measurement of
      flow-mediated dilatation (conduit artery, FMD) were evaluated. The IMT and number
      of carotid arteries with plaques (0, 1 or 2) were recorded using ultrasound at
      the baseline investigation and the follow-up visit conducted five years later.
      RESULTS: A total of 760 subjects had valid measurements of the IMT and carotid
      artery plaques at both the investigations conducted at 70 and 75 years of age.
      Neither the FMD nor EDV significantly predicted the change in IMT over five
      years. However, the FMD, but not EDV, was associated with the change in carotid
      plaque burden during the follow-up period, independent of classical risk factors,
      such as gender, waist circumference, fasting blood glucose, systolic and
      diastolic blood pressure, HDL- and LDL-cholesterol, serum triglycerides, BMI and
      smoking (OR 0.81 for a 1 SD change in FMD, 95%CI 0.68 to 0.95, p=0.010).
      CONCLUSIONS: The FMD was found to be a predictor of changes in the carotid plaque
      status, but not IMT, during the 5-year follow-up period, independent of classical
      cardiovascular risk factors.

PMID- 24126124
TI  - Infant diet, gender and the normative development of vagal tone and heart period
      during the first two years of life.
AB  - Relationships between early postnatal diet and the development of cardiac
      regulation were studied using resting vagal tone and heart period measures
      obtained quarterly during infancy and at 2years in 158 breast-fed, 159 milk
      formula-fed, and 148 soy formula-fed infants. Both measures increased across time
      for all groups. Heart period was greater in boys than in girls-particularly in
      soy-fed infants. Higher vagal tone in girls than in boys was not strongly
      influenced by diet. At 1 and 2years measures differed among boys (soy-fed>breast
      fed) but not among girls. Earlier slowing in breast-fed than in formula-fed
      infants in the rate of increase in vagal tone during infancy suggests that the
      timing of this developmental shift is sensitive to early infant diet. Finally,
      the findings do not indicate atypical development of cardiac activity in soy-fed
      infants that might be associated with estrogenic compounds in this formula. 

PMID- 24126125
TI  - The differences in frontal midline theta power between successful and
      unsuccessful basketball free throws of elite basketball players.
AB  - During the preparatory period of motor skill, attention is considered as one of
      the most vital factors for athletic performance. Electroencephalographic (EEG)
      indices, such as occipital alpha, have been employed to explore the psychological
      state during the preparatory period in elite athletes. The main purpose of this
      study was to investigate the differences in frontal midline theta (Fm theta)
      power during the aiming period between successful and unsuccessful basketball
      free throws. Fifteen skilled male basketball players were recruited and asked to
      perform free throws. Electroencephalogram (EEG) data were collected 2seconds
      prior to the initiation of the free throw and segmented into four 0.5-s epochs.
      The lower theta (theta1, 4-6Hz) and upper theta (theta2, 6-8Hz) power values was
      contrasted between the successful and unsuccessful throws. Two 2*4*6
      (performance*time*electrode) ANOVAs with repeated measures were conducted
      separately for theta1 and theta2 power. The results indicate that theta1 power at
      the Fz site and theta2 power at the Fz and the F4 sites fluctuated significantly
      during the preparatory period for an unsuccessful throw when compared with a
      successful throw. Additionally, a higher Fm theta2 power was observed at the
      beginning of the aiming period of a successful throw. This study suggests that a
      stable arousal and a relatively constant amount of attention to the task prior to
      motor execution may facilitate athletic performance. 

PMID- 24126126
TI  - Amphypterygium adstringens anacardic acid mixture inhibits quorum sensing
      controlled virulence factors of Chromobacterium violaceum and Pseudomonas
      aeruginosa.
AB  - BACKGROUND AND AIMS: Quorum sensing (QS) is a process of bacterial cell-cell
      communication that controls a large number of systems affecting pathogenicity.
      Interrupting this communication system can provide nonvirulent pathogenic
      bacteria. The aim of this study was to evaluate the anti-quorum sensing (anti-QS)
      potential of an anacardic acids mixture isolated from Amphipterygium adstringens,
      a medicinal plant known as "cuachalalate", to prevent the onset of bacterial
      infections as an alternate to antibiotics. METHODS: Initially we investigated the
      anti-QS activity of A. adstringens hexane extract (HE) by the inhibition of
      violacein production in Chromobacterium violaceum. From the active HE, an
      anacardic acid mixture (AAM) was obtained. The anti-quorum sensing activity of
      AAM was investigated by the rhamnolipid and pyocyanin production constraint as
      well as decrease of elastase activity, all being quorum sensing-controlled
      virulence factors expressed in the pathogenic bacteria Pseudomonas aeruginosa.
      RESULTS: HE induced a 91.6% of inhibition of the violecin production at 55 MUg/mL
      concentration, whereas AAM showed 94% of inhibition at 166 MUg/mL. In both cases,
      inhibition of violacein production did not affect the viability of the bacterium.
      AAM inhibited pyocyanin (86% at 200 MUg/mL) and rhamnolipid (91% at 500 MUg/mL)
      production in a dose/response form and decrease the elastase (75% at 500 MUg/mL)
      activity in P. aeruginosa without affecting its development. CONCLUSIONS: Because
      an anacardic acids mixture isolated from A. adstringens demonstrated anti-QS, it
      could be further exploited for novel molecules to treat the emerging infections
      of antibiotic-resistant bacterial pathogens.

PMID- 24126127
TI  - Polynucleotide phosphorylase (PNPase) is required for Salmonella enterica serovar
      Typhimurium colonization in swine.
AB  - The pnp gene encodes polynucleotide phosphorylase, an exoribonuclease involved in
      RNA processing and degradation. A mutation in the pnp gene was previously
      identified by our group in a signature-tagged mutagenesis screen designed to
      search for Salmonella enterica serovar Typhimurium genes required for survival in
      an ex vivo swine stomach content assay. In the current study, attenuation and
      colonization potential of a S. Typhimurium pnp mutant in the porcine host was
      evaluated. Following intranasal inoculation with 10(9) cfu of either the wild
      type S. Typhimurium chi4232 strain or an isogenic derivative lacking the pnp gene
      (n = 5/group), a significant increase (p < 0.05) in rectal temperature (fever)
      was observed in the pigs inoculated with wild-type S. Typhimurium compared to the
      pigs inoculated with the pnp mutant. Fecal shedding of the pnp mutant was
      significantly reduced during the 7-day study compared to the wild-type strain (p
      < 0.001). Tissue colonization was also significantly reduced in the pigs
      inoculated with the pnp mutant compared to the parental strain, including the
      tonsils, ileocecal lymph nodes, Peyer's Patch region of the ileum, cecum and
      contents of the cecum (p < 0.05). The data indicate that the pnp gene is required
      for S. Typhimurium virulence and gastrointestinal colonization of the natural
      swine host. 

PMID- 24126128
TI  - Electrical engram: how deep brain stimulation affects memory.
AB  - Deep brain stimulation (DBS) is a surgical procedure involving implantation of a
      pacemaker that sends electric impulses to specific brain regions. DBS has been
      applied in patients with Parkinson's disease, depression, and obsessive
      compulsive disorder (among others), and more recently in patients with
      Alzheimer's disease to improve memory functions. Current DBS approaches are based
      on the concept that high-frequency stimulation inhibits or excites specific brain
      regions. However, because DBS entails the application of repetitive electrical
      stimuli, it primarily exerts an effect on extracellular field-potential
      oscillations similar to those recorded with electroencephalography. Here, we
      suggest a new perspective on how DBS may ameliorate memory dysfunction: it may
      enhance normal electrophysiological patterns underlying long-term memory
      processes within the medial temporal lobe. 

PMID- 24126129
TI  - Information-seeking, curiosity, and attention: computational and neural
      mechanisms.
AB  - Intelligent animals devote much time and energy to exploring and obtaining
      information, but the underlying mechanisms are poorly understood. We review
      recent developments on this topic that have emerged from the traditionally
      separate fields of machine learning, eye movements in natural behavior, and
      studies of curiosity in psychology and neuroscience. These studies show that
      exploration may be guided by a family of mechanisms that range from automatic
      biases toward novelty or surprise to systematic searches for learning progress
      and information gain in curiosity-driven behavior. In addition, eye movements
      reflect visual information searching in multiple conditions and are amenable for
      cellular-level investigations. This suggests that the oculomotor system is an
      excellent model system for understanding information-sampling mechanisms. 

PMID- 24126130
TI  - Interoceptive inference, emotion, and the embodied self.
AB  - The concept of the brain as a prediction machine has enjoyed a resurgence in the
      context of the Bayesian brain and predictive coding approaches within cognitive
      science. To date, this perspective has been applied primarily to exteroceptive
      perception (e.g., vision, audition), and action. Here, I describe a predictive,
      inferential perspective on interoception: 'interoceptive inference' conceives of
      subjective feeling states (emotions) as arising from actively-inferred generative
      (predictive) models of the causes of interoceptive afferents. The model
      generalizes 'appraisal' theories that view emotions as emerging from cognitive
      evaluations of physiological changes, and it sheds new light on the
      neurocognitive mechanisms that underlie the experience of body ownership and
      conscious selfhood in health and in neuropsychiatric illness. 

PMID- 24126131
TI  - Incidental gastric gastrointestinal stromal tumor (GIST) in the excluded stomach
      after Roux- en-Y gastric bypass: a case report and review of the literature.

PMID- 24126132
TI  - Trace elements in scalp hair of children chronically exposed to volcanic activity
      (Mt. Etna, Italy).
AB  - The aim of this survey was to use scalp hair as a biomonitor to evaluate the
      environmental exposure to metals and metalloids of schoolchildren living around
      the Mt. Etna area, and to verify whether the degree of human exposure to trace
      elements is subject to changes in local environmental factors. Twenty trace
      elements were determined in 376 samples of scalp hair from schoolboys (11-13
      years old) of both genders, living in ten towns located around the volcanic area
      of Mt. Etna (Sicily). The results were compared with those (215 samples) from
      children living in areas of Sicily characterized by a different geological
      setting (reference site). As, U and V showed much higher concentrations at the
      volcanic site whereas Sr was particularly more abundant at the reference site.
      Linear Discriminant Analysis (LDA) indicated an Etna factor, made up of V, U and
      Mn, and a second factor, concerning the reference site, characterized by Ni and
      Sr, and to a lesser extent by Mo and Cd. Significant differences in element
      concentrations were also observed among three different sectors of Mt. Etna area.
      Young people living in the Mt. Etna area are naturally exposed to enhanced
      intakes of some metals (V, U, Mn) and non-metals (e.g., As) than individuals of
      the same age residing in other areas of Sicily, characterized by different
      lithologies and not influenced by volcanic activity. The petrographic nature of
      local rocks and the dispersion of the volcanic plume explain the differences,
      with ingestion of water and local food as the most probable exposure pathways.

PMID- 24126133
TI  - Assessment of potential improvements on regional air quality modelling related
      with implementation of a detailed methodology for traffic emission estimation.
AB  - The accuracy and precision of air quality models are usually associated with the
      emission inventories. Thus, in order to assess if there are any improvements on
      air quality regional simulations using detailed methodology of road traffic
      emission estimation, a regional air quality modelling system was applied. For
      this purpose, a combination of top-down and bottom-up approaches was used to
      build an emission inventory. To estimate the road traffic emissions, the bottom
      up approach was applied using an instantaneous emission model (Vehicle Specific
      Power - VSP methodology), and an average emission model (CORINAIR methodology),
      while for the remaining activity sectors the top-down approach was used. Weather
      Research and Forecasting (WRF) and Comprehensive Air quality (CAMx) models were
      selected to assess two emission scenarios: (i) scenario 1, which includes the
      emissions from the top-down approach; and (ii) scenario 2, which includes the
      emissions resulting from integration of top-down and bottom-up approaches. The
      results show higher emission values for PM10, NOx and HC, for scenario 1, and an
      inverse behaviour to CO. The highest differences between these scenarios were
      observed for PM10 and HC, about 55% and 75% higher (respectively for each
      pollutant) than emissions provided by scenario 2. This scenario gives better
      results for PM10, CO and O3. For NO2 concentrations better results were obtained
      with scenario 1. Thus, the results obtained suggest that with the combination of
      the top-down and bottom-up approaches to emission estimation several improvements
      in the air quality results can be achieved, mainly for PM10, CO and O3. 

PMID- 24126134
TI  - Soil ingestion rate determination in a rural population of Alberta, Canada
      practicing a wilderness lifestyle.
AB  - The inadvertent ingestion of contaminated soil can be a major pathway for
      chemical exposure to humans. Few studies to date have quantified soil ingestion
      rates to develop exposure estimates for human health risk assessments (HHRA), and
      almost all of those were for children in suburban/urban environments. Here we
      employed a quantitative mass balance tracer approach on a rural population
      practicing outdoor activities to estimate inadvertent soil ingestion. This study
      followed 9 subjects over a 13 day period in Cold Lake, Alberta, near the largest
      in situ thermal heavy oil (bitumen) extraction operation in the world. The mean
      soil ingestion rate in this study using Al Ce, La, and Si tracers was 32 mg d(
      1), with a 90th percentile of 152 mg d(-1) and median soil ingestion rate of 18
      mg d(-1). These soil ingestion values are greater than the standard recommended
      soil ingestion rates for HHRA from Health Canada, and are similar to soil
      ingestion estimates found in the only other study on a rural population.

PMID- 24126135
TI  - Sex-specific activity and function of hypothalamic nonapeptide neurons during
      nest-building in zebra finches.
AB  - Vertebrate species from fish to humans engage in a complex set of preparatory
      behaviors referred to as nesting; yet despite its phylogenetic ubiquity, the
      physiological and neural mechanisms that underlie nesting are not well known. We
      here test the hypothesis that nesting behavior is influenced by the vasopressin
      oxytocin (VP-OT) peptides, based upon the roles they play in parental behavior in
      mammals. We quantified nesting behavior in male and female zebra finches
      following both peripheral and central administrations of OT and V1a receptor (OTR
      and V1aR, respectively) antagonists. Peripheral injections of the OTR antagonist
      profoundly reduce nesting behavior in females, but not males, whereas comparable
      injections of V1aR antagonist produce relatively modest effects in both sexes.
      However, central antagonist infusions produce no effects on nesting, and OTR
      antagonist injections into the breast produce significantly weaker effects than
      those into the inguinal area, suggesting that antagonist effects are mediated
      peripherally, likely via the oviduct. Finally, immunocytochemistry was used to
      quantify nesting-induced Fos activation of nonapeptide neurons in the
      paraventricular and supraoptic nuclei of the hypothalamus and the medial bed
      nucleus of the stria terminalis. Nest-building induced Fos expression within
      paraventricular VP neurons of females but not males. Because the avian forms of
      OT (Ile(8)-OT; mesotocin) and VP (Ile(3)-VP; vasotocin) exhibit high affinity for
      the avian OTR, and because both peptide forms modulate uterine contractility, we
      hypothesize that nesting-related stimuli induce peptide release from
      paraventricular vasotocin neurons, which then promote female nesting via
      peripheral feedback from OTR binding in the oviduct uterus.

PMID- 24126137
TI  - Mechanisms by which neonatal testosterone exposure mediates sex differences in
      impulsivity in prepubertal rats.
AB  - Neonatal testosterone, either acting directly or through its conversion to
      estradiol, can exert organizational effects on the brain and behavior. The goal
      of the current study was to examine sex differences and determine the role of
      neonatal testosterone on prefrontal cortex-dependent impulsive choice behavior in
      prepubertal rats. Male and female prepubertal rats were tested on the delay-based
      impulsive choice task. Impulsive choice was defined as choosing an immediate
      small food reward over a delayed large reward. In a first experiment to examine
      sex differences, males made significantly more impulsive choices than did
      females. In a second experiment to examine the organizational effects of
      testosterone, females treated with neonatal testosterone made significantly more
      impulsive choices than did control females and their performance was
      indistinguishable from that of control males. In a third experiment to determine
      if the effect of testosterone on performance is due to the actions of androgens
      or estrogens through its conversion to estradiol, males treated neonatally with
      the aromatase inhibitor formestane, which blocks the conversion of testosterone
      to estradiol, females treated neonatally with the non-aromatizable androgen
      dihydrotestosterone, and females treated neonatally with estradiol made
      significantly more impulsive choices than did control females and their
      performance was indistinguishable from that of control males. Results indicate
      that male pubertal rats display increased impulsive choice behavior as compared
      to females, that this sex difference results from organizing actions of
      testosterone during the neonatal period, and that this effect can result from
      both androgenic and estrogenic actions.

PMID- 24126136
TI  - Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure
      predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus
      auratus).
AB  - In the U.S. and worldwide anabolic/androgenic steroid use remains high in the
      adolescent population. This is concerning given that anabolic/androgenic steroid
      use is associated with a higher incidence of aggressive behavior during exposure
      and anxiety during withdrawal. This study uses pubertal Syrian hamsters
      (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral
      relationship exists between anabolic/androgenic steroid-induced aggression and
      anxiety across adolescent exposure and withdrawal. In the first experiment, we
      examined aggression and anxiety during adolescent anabolic/androgenic steroid
      exposure and withdrawal. Adolescent anabolic/androgenic steroid administration
      produced significant increases in aggression and decreases in anxiety during the
      exposure period followed by significant decreases in aggression and increases in
      anxiety during anabolic/androgenic steroid withdrawal. In a second experiment,
      anabolic/androgenic steroid exposed animals were separated into groups based on
      their aggressive response during the exposure period and then tested for anxiety
      during exposure and then for both aggression and anxiety during withdrawal. Data
      were analyzed using a within-subjects repeated measures predictive analysis.
      Linear regression analysis revealed that the difference in aggressive responding
      between the anabolic/androgenic steroid exposure and withdrawal periods was a
      significant predictor of differences in anxiety for both days of testing.
      Moreover, the combined data suggest that the decrease in aggressive behavior from
      exposure to withdrawal predicts an increase in anxiety-like responding within
      these same animals during this time span. Together these findings indicate that
      early anabolic/androgenic steroid exposure has potent aggression- and anxiety
      eliciting effects and that these behavioral changes occur alongside a predictive
      relationship that exists between these two behaviors over time.

PMID- 24126138
TI  - Nrf2 is a potential therapeutic target in radioresistance in human cancer.
AB  - Radiation therapy can effectively kill cancer cells through ROS generation.
      Cancer cells with upregulated antioxidant systems can develop high
      radioresistance ability, and the transcription factor NF-E2-related factor 2
      (Nrf2) is a key regulator of the antioxidant system. Currently, there are
      numerous data indicating the important role of Nrf2 in cancer radioresistance. In
      this review, we summarize the aberrant regulation of Nrf2 in radioresistant cells
      and discuss the effects and underlying mechanism of Nrf2 in promoting
      radioresistance. These findings suggest that Nrf2 might be a potential
      therapeutic target in cancer radiation resistance or a promising radioprotector
      for normal organs during radiation therapy in the future.

PMID- 24126139
TI  - Fennel-like nanoaggregates based on polysaccharide derivatives and their
      application in drug delivery.
AB  - Biodegradable polymeric nanoparticles, which hold hierarchical morphologies, are
      of importance for controlled drug delivery. In this work, nanoparticles with
      fennel-like morphology were prepared from graft copolymers of
      hydroxyethylcellulose and poly(p-dioxane). The effect of microstructure
      parameters on the morphological transition of the nano-aggregates was studied and
      the nanoparticles were investigated as a carrier of hydrophobic drug. The
      morphology and drug release property of the nanoparticles were found to be
      related with the degree of substitution and molecular weight of graft chain of
      the copolymer. 

PMID- 24126140
TI  - Incident fractures in HIV-infected individuals: a systematic review and meta
      analysis.
AB  - OBJECTIVE(S): Some but not all studies indicate that individuals with HIV
      infection are at an increased risk of fracture. We systematically reviewed the
      literature to investigate whether incidence of fracture (both overall and
      fragility) differs between individuals with and without HIV. DESIGN: A systematic
      review and meta-analysis. METHODS: Medline, Scopus and the Cochrane Library
      databases for all studies ever published up to 28 September 2012 and
      electronically available conference abstracts from CROI, ASBMR, IAS and AIDS were
      searched. All studies reporting incidence of all fracture and fragility fracture
      in HIV-infected adults were included. A random effects model was used to
      calculate pooled estimates of incidence rate ratios (IRRs) for studies that
      presented data for HIV-infected and controls. For all studies, incidence rates of
      fracture and predictors of fracture among HIV-infected individuals were
      summarized. RESULTS: Thirteen eligible studies were analysed, of which seven
      included controls. Nine studies reported all incident fractures and 10 presented
      incident fragility fractures. The pooled IRR was 1.58 [95% confidence interval
      (CI) 1.25-2.00] for all fracture and 1.35 (95% CI 1.10-1.65) for fragility
      fracture. Smoking, white race and older age were consistent predictors for
      fragility fractures. CONCLUSION: Our results indicate that HIV infection is
      associated with a modest increase in incident fracture. Future research should
      focus on clarifying risk factors, designing appropriate interventions and the
      long-term implications of this increased risk for an ageing HIV-infected
      population.

PMID- 24126141
TI  - Various conotoxin diversifications revealed by a venomic study of Conus flavidus.
AB  - Conotoxins are peptide neurotoxins produced by predatory cone snails. They are
      mostly cysteine-rich short peptides with remarkable structural diversity. The
      conserved signal peptide sequences of their mRNA-encoded precursors have enabled
      the grouping of known conotoxins into a limited number of superfamilies. However,
      the conotoxins within each superfamily often present variable sequences, cysteine
      frameworks, and post-translational modifications. To understand better how
      conotoxins are diversified, we performed a venomic study with C. flavidus, an
      uninvestigated vermivorous Conus species, by combining transcriptomic and
      proteomic analyses. In order to obtain the full-length conotoxin sequences,
      protease digestion was not performed with the venom extraction prior to spectra
      acquisition via tandem mass spectrometry (MS/MS). Because conotoxins are produced
      from mRNA-encoded precursors by means of proteolytic cleavage, nonspecific
      digestion of precursors was applied during the database search. Special attention
      was also paid in interpreting the MS/MS spectra. All together, these analyses
      identified 69 nonredundant cDNA sequences and 31 conotoxin components with
      confident MS/MS spectra. A new Q-superfamily was also identified. More
      importantly, this study revealed that conotoxin-encoding transcripts are
      diversified by hypermutation, fragment insertion/deletion, and mutation-induced
      premature termination, and that a single mRNA species can produce multiple toxin
      products through alternative post-translational modifications and alternative
      cleavages of the translated precursor. These multiple diversification strategies
      at different levels may explain, at least in part, the diversity of conotoxins,
      and provide the basis for further investigation. 

PMID- 24126142
TI  - Defining the protein-protein interaction network of the human hippo pathway.
AB  - The Hippo pathway, which is conserved from Drosophila to mammals, has been
      recognized as a tumor suppressor signaling pathway governing cell proliferation
      and apoptosis, two key events involved in organ size control and tumorigenesis.
      Although several upstream regulators, the conserved kinase cascade and key
      downstream effectors including nuclear transcriptional factors have been defined,
      the global organization of this signaling pathway is not been fully understood.
      Thus, we conducted a proteomic analysis of human Hippo pathway, which revealed
      the involvement of an extensive protein-protein interaction network in this
      pathway. The mass spectrometry data were deposited to ProteomeXchange with
      identifier PXD000415. Our data suggest that 550 interactions within 343 unique
      protein components constitute the central protein-protein interaction landscape
      of human Hippo pathway. Our study provides a glimpse into the global organization
      of Hippo pathway, reveals previously unknown interactions within this pathway,
      and uncovers new potential components involved in the regulation of this pathway.
      Understanding these interactions will help us further dissect the Hippo signaling
      pathway and extend our knowledge of organ size control. 

PMID- 24126144
TI  - Genomic and systems approaches to translational biomarker discovery in
      immunological diseases.
AB  - The high failure rate of new therapeutic mechanisms tested in clinical
      development has spurred an upsurge in research dedicated to discovering biomarker
      readouts that can improve decision-making. Increasingly, systems biology and
      genomic technologies, such as transcriptional profiling, are being leveraged to
      aid in the discovery of biomarker readouts. For inflammatory and immunological
      diseases, such as rheumatoid arthritis (RA) and asthma, progress has been made in
      developing biomarkers to monitor disease activity, prediction of response to
      therapy, and pharmacodynamic (PD) measurements. In this review, we discuss recent
      successes and challenges in these endeavors, highlighting the importance of human
      clinical studies of standard-of-care treatments in control subjects and patients
      with disease as the most direct path toward identifying useful translational
      biomarkers for clinical development. 

PMID- 24126143
TI  - Quality measures of imaging mass spectrometry aids in revealing long-term
      striatal protein changes induced by neonatal exposure to the cyanobacterial toxin
      beta-N-methylamino-L-alanine (BMAA).
AB  - Many pathological processes are not directly correlated to dramatic alterations
      in protein levels. The changes in local concentrations of important proteins in a
      subset of cells or at specific loci are likely to play a significant role in
      disease etiologies, but the precise location might be unknown, or the
      concentration might be too small to be adequately sampled for traditional
      proteomic techniques. Matrix-assisted laser desorption ionization (MALDI) imaging
      mass spectrometry (IMS) is a unique analytical method that combines analysis of
      multiple molecular species and of their distribution in a single platform. As
      reproducibility is essential for successful biomarker discovery, it is important
      to systematically assess data quality in biologically relevant MALDI IMS
      experiments. In the present study, we applied four simple tools to study the
      reproducibility for individual sections, within-group variation, and between
      group variation of data acquired from brain sections of 21 animals divided into
      three treatment groups. We also characterized protein changes in distinct regions
      of the striatum from six-month-old rats treated neonatally (postnatal days 9-10)
      with the cyanobacterial toxin beta-N-methylamino-l-alanine (BMAA), which has been
      implicated in neurodegenerative diseases. The results showed that optimized
      experimental settings can yield high-quality MALDI IMS data with relatively low
      variation (14% to 15% coefficient of variance) that allow the characterization of
      subtle changes in protein expression in various subregions of the brain. This was
      further exemplified by the dose-dependent reduction of myelin basic protein in
      the caudate putamen and the nucleus accumbens of adult rats neonatally treated
      with BMAA (150 and 460 mg/kg). The reduction in myelin basic protein was
      confirmed through immunohistochemistry and indicates that developmental exposure
      to BMAA may induce structural effects on axonal growth and/or directly on the
      proliferation of oligodendrocytes and myelination, which might be important for
      the previously shown BMAA-induced long-term cognitive impairments. 

PMID- 24126145
TI  - [Results of arthrodiastasis in postraumatic ankle osteoarthritis in a young
      population: prospective comparative study].
AB  - INTRODUCTION: The most common cause of osteoarthritis of the ankle is post
      traumatic, and although tibiotalar arthrodesis remains the surgical gold
      standard, a number of techniques have been described to preserve joint mobility,
      such as joint distraction arthroplasty or arthrodiastasis. OBJECTIVE: To evaluate
      the functional outcome and changes in Visual Analogue Scale (VAS) for pain after
      the application of the distraction arthroplasty for post-traumatic ankle
      osteoarthritis. PATIENTS AND METHODS: A prospective comparative study of a group
      of 10 young patients with post-traumatic ankle osteoarthritis treated by
      synovectomy and arthrodiastasis, compared to a control group of 10 patients
      treated by isolated synovectomy. Results were calculated using the AOFAS scale
      and the VAS for pain before and after treatment. RESULTS: As regards the pain
      measured by VAS, no difference was observed between the two groups before surgery
      (P=.99), but there was a difference at 3 months (P<.001), 6 months (P=.005), and
      12 months (P=.006). No differences were observed in the AOFAS scale between the
      two groups before surgery (P=.99), or at 3 months (P<.99), but there was a
      difference at 6 months (P<.001). CONCLUSIONS: Ankle arthrodiastasis is effective
      in reducing pain in post-traumatic ankle arthropathy, and is superior to isolated
      synovectomy.

PMID- 24126146
TI  - [Tranexamic acid in orthopedic surgery].
AB  - Perioperative bleeding may require blood transfusions, which are sometimes not
      without complications and risks, with the subsequent increase in health care
      costs. Among other prevention methods, treatment with tranexamic acid (ATX) has
      shown to be effective in reducing surgical blood loss, especially in the
      immediate postoperative period. In this regard, studies evaluating ATX in
      orthopedic surgery show that it is effective and safe when administered
      intravenously or intra-articularly. The usual evaluated intravenous doses range
      between 10mg/Kg and 20mg/kg or a fixed dose of 1g to 2g; while intra-articularly,
      it varies between 250 mg and 3g. ATX, as an anti-fibrinolytic has a potential
      thrombotic effect, thus it is contraindicated in those patients at risk or with a
      history of thrombosis. Its topical administration may be safer, but studies are
      needed to confirm this.

PMID- 24126147
TI  - [External stability of the elbow after surgical treatment of epicondylitis.
      Presentation of a case].
AB  - Elbow instability is a difficult to diagnose condition in certain cases, and
      could lead to some problems that limit daily functioning, such as joint blocks,
      bumps, projections, muscle weakness, and persistent pain. A case is presented of
      a patient with a clinical picture of epicondylitis, with a previous history of a
      fall on the affected arm. As there was no improvement after performing
      conventional non-aggressive treatment, surgery was performed on the affected
      tendon. The outcome of this was persistent pain and clinical instability of the
      elbow that ended up requiring surgery to reconstruct the ligament over the
      external complex. In follow-up 6 months after the operation, the clinical
      instability had disappeared, but there was still external discomfort and a 30
      degrees  extension deficit. When faced with a picture of epicondylitis with a
      previous injury that does not respond to conventional therapies, it is important
      to take into account the possibility of an underlying elbow instability, ruling
      this out with a correct physical examination and, where necessary, with the
      appropriate complementary tests. 

PMID- 24126148
TI  - [Inveterate subaxial cervical dislocations: a discussion on the best therapeutic
      strategy].
AB  - It is difficult to decide the appropriate treatment for inveterate cervical
      dislocations because of the difficulty of their reduction, as well as due to the
      risk of inducing iatrogenic injuries during this reduction. The literature on the
      most appropriate surgical strategy for their management is also limited as well
      as controversial. We report one clinical case treated in the Spine Unit of the
      Orthopedic Surgery and Trauma Service of the University Hospital of Santiago de
      Compostela, discussing the currently most used treatment options, the anterior
      posterior-anterior and the posterior-anterior-posterior approach. After analyzing
      the results, it could be concluded that the surgical approach to these lesions is
      generally difficult, with any of two techniques described above being suitable,
      but always with the precaution to remove the entire affected intervertebral disc
      before axial correction maneuvers, thus avoiding the risk of extrusion into the
      medullary canal. After the surgical procedure, a proper release and reduction of
      the joint facets should be performed, sometimes with the need to add osteotomies
      in them.

PMID- 24126149
TI  - Chemotherapy-induced cognitive deficits, white matter pathologies and cytokines.

PMID- 24126150
TI  - Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6
      production in obesity.
AB  - Obesity is considered a chronic inflammatory condition that enhances the risk of
      numerous inflammatory diseases, including diabetes and cardiovascular disease.
      Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents,
      but the exact functions of GCs in obesity-related inflammation are unknown.
      Therefore, the objective of this study was to examine the inhibitory effect of an
      exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced
      IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese
      subjects compared to normal-weight subjects. Blood samples were drawn from 14
      obese (BMI>30 kg/m(2)) and 14 normal-weight (BMI<25 kg/m(2)) subjects. Plasma
      cortisol, TNF-alpha and IL-6 levels, and insulin resistance (HOMA-IR) were
      quantified. Subjects' PBMCs (1*10(6) cells/mL) were isolated and cultured with
      leptin (18.75 and 250 ng/mL) or LPS (10ng/mL) in the presence of DEX (0, 10(-8),
      10(-7), and 10(-6) M), a synthetic GC, for 24 h; IL-6 levels and GC sensitivity
      (IC50) were assessed in the cultured supernatants. No differences in the plasma
      cortisol levels were found between the two groups. We found that obese subjects
      showed greater leptin- and LPS-induced IL-6 production compared to normal-weight
      subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6
      production (IC50) was not different between the two groups. However, the IC50 of
      DEX for LPS-induced was correlated with BMI, waist circumference, and hip
      circumference. These findings suggest that reduced GC sensitivity may be an
      important mechanism in the up-regulation of selected obese inflammation.

PMID- 24126151
TI  - The effects of exercise on vaccination responses: a review of chronic and acute
      exercise interventions in humans.
AB  - Vaccination programs, although feted for success in reducing infectious disease
      morbidity and mortality, are limited by vaccine efficacy, which is particularly
      problematic in populations with reduced immune function. Exercise has been
      identified as a behavioural factor that can improve immune function in some
      settings and cohorts, and therefore, in the setting of vaccination, it may serve
      as an adjuvant for immune responses. Here, we summarise the body of evidence that
      has investigated the effects of chronic or acute exercise interventions on
      vaccination responses. A systematic search of the literature was conducted
      including six major databases. Randomised control trials (RCTs), cross-sectional
      and observational studies that involved a variety of population samples and that
      employed any modality or intensity of acute exercise or chronic training prior to
      vaccine administration and measured any immune response were included. Twenty
      trials met the inclusion criteria for this review. Nine studies investigated the
      effect of acute exercise on the immune response to vaccination, whilst the
      remaining eleven studies investigated the effect of chronic exercise. Most of the
      current published literature suggests that exposure to either acute or chronic
      exercise significantly augments the immune response to vaccination. The clinical
      importance of this adjuvant action of exercise, if any, as well as variability in
      responsiveness across different cohorts, dose-response relationships and the
      optimal exercise modality to employ for this indication deserve further study. 

PMID- 24126152
TI  - Dry eye disease: prevalence, distribution and determinants in a hospital-based
      population.
AB  - OBJECTIVES: To determine the prevalence, distribution and risk factors for dry
      eye disease (DED) in a tertiary ophthalmic outpatient population. METHODS: The
      study was a cross-sectional descriptive hospital-based survey conducted at the
      Eye clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu, between
      September and December, 2011. The participants comprised adult ophthalmic
      outpatients aged 18 years or older. Participants' sociodemographic data were
      obtained. Dry eye disease was assessed subjectively with the Ocular Surface
      Disease Index (OSDI) questionnaire; and objectively with Schirmer's test and Tear
      film Break-up Time (TBUT). An OSDI score of >= 50 with a TBUT of <10s or
      Schirmer's test reading of <10mm was considered diagnostic of DED. Descriptive
      and analytical statistics were performed. In all comparisons, a p<0.05 was
      considered statistically significant. RESULTS: The participants (n=402) comprised
      193 males and 209 females who were aged 50.1 +/- 19.06 SD years (range 18-94
      years). The majorities of the participants were married - 74.1%, possessed formal
      education - 86.0% and were civil servants - 33.6%. The prevalence of DED was
      19.2%. Dry eye disease was significantly associated with age>40 years (OR 1.88,
      95% CI 1.06-3.35, p=0.0004), non-possession of formal education (OR 0.40, 95% CI
      0.21-0.74, p=0.001) but not gender (OR 1.48, 95% CI 0.89-2.46, p=0.158).
      CONCLUSION: The prevalence of DED among ophthalmic outpatients at UNTH, Enugu, is
      comparatively high. Older age and illiteracy are predictors of DED. There is need
      for high index of diagnostic suspicion to prevent sight-threatening complications
      of DED.

PMID- 24126153
TI  - UV-vis light transmittance through tinted contact lenses and the effect of color
      on values.
AB  - PURPOSE: To assess the transmittance, in the 200-700nm electromagnetic radiation
      spectrum, by popularly used tinted soft contact lenses (CLs). METHOD: The spectra
      transmittances of ultraviolet (UV)-blocking (I Day Acuvue Define, Freshlook ONE
      DAY) and non-UV-blocking (Durasoft 3, Tutti, and NeoCosmo) tinted soft CLs were
      tested. The transmittance of each lens, including nine different colors of
      Freshlook CL was recorded on spectrophotometer, and the data used to also
      calculate a UV protection factor (PF) for each lens brand tested, with a higher
      value indicating a higher level of protection. RESULTS: The UV-blocking CLs
      significantly reduced UVC, UVB & UVA transmission and thereby meet the American
      National Standards Institution standard for class 2 UV blockers: a maximum of 30%
      transmittance of UVA and 5% transmittance of UVB wavelengths. In contrast, the
      Durasoft 3, Tutti, and NeoCosmo CLs demonstrated negligible UV-blockage. The
      Acuvue Define CL offered the greatest protection from UVC (PF=69) and UVB
      (PF=55), but with only 35% luminous transmittance, while the Freshlook CL
      (especially gemstone green) offered the best protection from UVA (PF=24) and
      showed about 55% translucency. Overall, the UV-blocking CLs performed equally
      well across the UV spectrum. Different colors of Freshlook CL transmitted
      statistically and clinically significantly different amounts of visible light but
      similar amounts of UVR. CONCLUSION: Freshlook and Acuvue Define CLs which are
      designated as UV-blockers significantly reduced UVR transmission to safe levels
      whereas Tutti, NeoCosmo and Durasoft 3 did not. Transmission within the Freshlook
      CL family was more dependent on color in the visible light spectrum, but not in
      the UV-spectrum, where the gemstone green performing best among the tested
      colors.

PMID- 24126154
TI  - Enhanced start-up of anaerobic facultatively autotrophic biocathodes in
      bioelectrochemical systems.
AB  - Biocathodes in bioelectrochemical systems (BESs) can be used to convert CO2 into
      diverse organic compounds through a process called microbial electrosynthesis.
      Unfortunately, start-up of anaerobic biocathodes in BESs is a difficult and time
      consuming process. Here, a pre-enrichment method was developed to improve start
      up of anaerobic facultatively autotrophic biocathodes capable of using cathodes
      as the electron donor (electrotrophs) and CO2 as the electron acceptor. Anaerobic
      enrichment of bacteria from freshwater bog sediment samples was first performed
      in batch cultures fed with glucose and then used to inoculate BES cathode
      chambers set at -0.4V (versus a standard hydrogen electrode; SHE). After two
      weeks of heterotrophic operation of BESs, CO2 was provided as the sole electron
      acceptor and carbon source. Consumption of electrons from cathodes increased
      gradually and was sustained for about two months in concert with a significant
      decrease in cathode chamber headspace CO2. The maximum current density consumed
      was -34 +/- 4 mA/m(2). Biosynthesis resulted in organic compounds that included
      butanol, ethanol, acetate, propionate, butyrate, and hydrogen gas. Bacterial
      community analyses based on 16S rRNA gene clone libraries revealed Trichococcus
      palustris DSM 9172 (99% sequence identity) as the prevailing species in
      biocathode communities, followed by Oscillibacter sp. and Clostridium sp.
      Isolates from autotrophic cultivation were most closely related to Clostridium
      propionicum (99% sequence identity; ZZ16), Clostridium celerecrescens (98-99%;
      ZZ22, ZZ23), Desulfotomaculum sp. (97%; ZZ21), and Tissierella sp. (98%; ZZ25).
      This pre-enrichment procedure enables simplified start-up of anaerobic
      biocathodes for applications such as electrofuel production by facultatively
      autotrophic electrotrophs.

PMID- 24126155
TI  - Characterization of five terminator regions that increase the protein yield of a
      transgene in Saccharomyces cerevisiae.
AB  - Strong terminator regions could be used to improve metabolically engineered
      yeasts by increasing the target enzyme protein yields above those achieved with
      traditional terminator regions. We recently identified five strong terminator
      regions (RPL41Bt, RPL15At, DIT1t, RPL3t, and IDP1t) in a comprehensive analysis
      of Saccharomyces cerevisiae. The effect of the terminator regions was analyzed by
      measuring the protein production of a linked transgene, and was shown to be twice
      that of a traditional terminator region (PGK1t). Here, we investigated whether
      the activity of the terminator regions is affected by exchange of a strong
      promoter or reporter in the linked transgene, carbon source for cell growth,
      stress factors, host yeast strain, or stage of the growth phase. Our results
      indicate that the activities of all five terminator regions were twice that of
      PGK1t in all conditions tested. In addition, we demonstrated that the strong
      activity of these terminator regions could be used to improve secretory
      production of endoglucanase II derived from Tricoderma ressei, and that the DIT1t
      strain was the best of the five strains for this purpose. We therefore propose
      that DIT1t, and the four other terminator regions, could be applied to the
      development of improved metabolically engineered yeasts.

PMID- 24126156
TI  - [Management of bilateral hand amputations in low-resources setting: the
      Krukenberg procedure is still indicated].
AB  - Double hand amputation leads to complete loss of prehensive function and touch
      sense. Patients become totally dependent on others for survival. In developing
      countries, where sophisticated myoelectric prosthesis are not available, the
      Krukenberg procedure gives to these patients elementary self-sufficiency for
      daily-life. This procedure can be performed in low-resources setting and requires
      minimal rehabilitation. However, patient selection and preparation are critical
      because of an unattractive aesthetic aspect which limits this operation use in
      occidental countries. 

PMID- 24126157
TI  - Brainwide distribution and variance of amyloid-beta deposits in tg-ArcSwe mice.
AB  - Transgenic mice carrying the Arctic (E693G) and Swedish (KM670/6701NL) amyloid
      beta precursor protein (AbetaPP) develop amyloid-beta (Abeta) deposits in the
      brain that resemble Alzheimer's disease neuropathology. Earlier studies of this
      model have documented morphologic features in selected parts of the cerebral
      cortex and hippocampus, but the spatial distribution within the brain and
      variance of Abeta deposits within a group of tg-ArcSwe mice is unknown. Using
      immunohistochemistry and brainwide microscopic analysis of 12-month-old tg-ArcSwe
      mice, we show that Abetax-40 plaque deposits are consistently present in the
      cerebral cortex, hippocampus, and thalamus and variably present in other regions.
      Using quantitative image analysis, we demonstrated that the average Abeta burden
      in the cortex and hippocampus is similar across animals, with coefficients of
      variance of 22% and 25%, respectively. This indicates that interventional studies
      of tg-ArcSwe mice are feasible using region-of-interest comparisons and that
      interventional trials require larger group sizes than commonly used. We also
      present an online atlas providing access to images showing the detailed
      characteristics and spatial distribution patterns of Abetax-40 labeling.

PMID- 24126158
TI  - Human superoxide dismutase 1 overexpression in motor neurons of Caenorhabditis
      elegans causes axon guidance defect and neurodegeneration.
AB  - Strong evidence indicates that mutant Cu, Zn-superoxide dismutase 1 (SOD1) exerts
      toxic effect on motor neurons in amyotrophic lateral sclerosis (ALS). However,
      the nature of mutant SOD1-mediated motor neuron degeneration is poorly
      understood. To provide new insight into the mechanism by which mutant SOD1
      induces motor neuron injury, we developed novel Caenorhabditis elegans models of
      ALS. Expression of human wild type or G93A SOD1 specifically in motor neurons of
      C. elegans caused progressive locomotion defect and paralytic phenotype, which
      recapitulate some characteristic features of ALS including age-dependent motor
      dysfunction and degeneration of motor neurons associated with SOD1 aggregation.
      In addition, the motor neuron loss is independent of cell death protein 3 (CED
      3)/cell death protein 4 (CED-4) caspase pathway. We also found that before motor
      neurons began to die in adulthood, axon guidance defect of motor neuron appeared
      during the development stages. When green fluorescent protein (GFP)-tagged
      proteins related to axon guidance were examined in motor neurons, a significantly
      decreased density and number of GFP-tagged puncta were observed in the transgenic
      worms. Our models mimic axon developmental defect and the adult-onset
      degeneration of motor neurons in ALS. Using this model, we uncovered the cell
      autonomous damage caused by human SOD1 to motor neurons in vivo, and provided a
      new insight into the developmental defect mechanism that may contribute to motor
      neuron degeneration in ALS.

PMID- 24126159
TI  - Clinicogenetic study of GBA mutations in patients with familial Parkinson's
      disease.
AB  - The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease
      (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147
      Japanese familial PD (FPD) patients from 144 families and 100 unrelated control
      subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for
      known Gaucher disease mutations, suggesting that GBA heterozygous mutations are
      strongly associated with FPD (odds ratio = 22.9, 95% confidence interval = 3.1
      171.2). The frequency was significantly higher in autosomal dominant PD (ADPD)
      compared with autosomal recessive PD. According to clinical assessments, PD
      patients with GBA mutations exhibited typical manifestations of PD or dementia
      with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric
      problems and/or cognitive decline. Interestingly, they also presented with
      reduced myocardial (123)I-metaiodobenzylguanidine uptake. Our findings suggest
      that heterozygous GBA mutations are strong risk factors in FPD, especially for
      autosomal dominant PD. Some patients with GBA heterozygous mutations develop
      clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body
      formation, resulting in more severe PD or DLB phenotypes that are inherited in
      families.

PMID- 24126160
TI  - Rare and common variants in the Apolipoprotein E gene in healthy oldest old.
AB  - Apolipoprotein E (APOE) alleles are associated with longevity in genome-wide
      scans, with epsilon4 correlated with shorter life, and epsilon2 with longer life,
      than epsilon3. We hypothesized that rare APOE variants with large individual
      effects might also contribute to long-term good health. The APOE exons and
      promoter were resequenced in DNA samples from 376 healthy oldest old aged >= 85
      yrs with no self-reported history of cancer, cardiovascular disease, diabetes,
      major pulmonary disease or Alzheimer disease ("Super-Seniors") and 376 population
      based controls aged 41-54. Forty variants were observed: 32 were rare (minor
      allele frequency <2%); 9 were nonsynonymous. Controls were more likely to have an
      epsilon4 allele (Pearson chi(2) = 6.61, p = 0.04). Among the Super-Seniors, APOE
      allele status was not associated with body mass index or Mini Mental State
      Examination score. There was no excess of rare APOE variants in healthy oldest
      old compared with midlife controls, or vice-versa; however, this does not rule
      out an effect of some variants on ApoE function. Our findings were consistent
      with epsilon4 being a risk factor for early mortality.

PMID- 24126161
TI  - Absence of A673T variant in APP gene indicates an alternative protective
      mechanism contributing to longevity in Chinese individuals.
AB  - A673T, a rare variant in the amyloid-beta precursor protein gene, shows a
      protective potential against Alzheimer's disease (AD) and age-related cognitive
      decline in an Icelandic population. Although A673T was observed independently in
      a Finnish population, this variant was absent in 8721 Asian subjects. The
      conflicting observations suggest that the contribution of A673T may be confined
      to Europeans and Americans rather than Asians. Nevertheless, A673T confers a
      protective function against AD and thus may be observed only in longevity
      subjects; thus it is not surprising to see its absence when the general
      populations or the patient cohorts were considered. To test whether the A673T
      contributes to the Chinese population, 1237 healthy longevity subjects (mean age
      96.9 years) and 1404 matched younger controls (mean age 44.2 years) were
      genotyped for the variant. Our study failed to observe this variant in either the
      longevity subjects or the controls. Given the previous observation from Asians,
      our results suggest that the A673T variant is not involved in longevity in
      Chinese individuals; some other protective mechanisms may contribute to a lower
      incidence of AD in Chinese nonagenerians and centenarians. 

PMID- 24126162
TI  - Positron emission tomography imaging of 5-hydroxytryptamine1B receptors in
      Parkinson's disease.
AB  - Impairment of the central serotonin system in Parkinson's disease (PD) has been
      shown postmortem and in vivo with positron emission tomography (PET). The aim of
      this PET study was to examine and compare the availability of the 5
      hydroxytryptamine (5-HT)(1B)-receptor subtype in patients with PD and age-matched
      control subjects. Twelve control subjects and 12 PD patients were examined with
      PET using the 5-HT(1B)-radioligand [(11)C]AZ10419369. In PD patients, 5-HT(1B)
      receptor availability in the right orbitofrontal cortex was lower than in control
      subjects. A statistically significant negative correlation between 5-HT(1B)
      receptor availability and age was obtained for the right temporal cortex in
      control subjects and for the right midbrain and left parahippocampal gyrus in PD
      patients. The lower regional 5-HT(1B)-receptor availability is in line with
      previous studies showing a decrease of serotonin imaging markers in PD and
      corroborates a role of the serotonin system in the pathophysiology of PD. The
      demonstrated age effect on 5-HT(1B) receptors suggest a physiologic and PD
      related decline of serotonin function, indicating the importance of controlling
      for age in clinical studies.

PMID- 24126163
TI  - Tissue plasminogen activator arrests Alzheimer's disease pathogenesis.
AB  - The progressive deposition of amyloid-beta (Abeta) in the brain is a pathologic
      feature of Alzheimer's disease (AD). This study was aimed to determine whether
      endogenous tissue plasminogen activator (tPA) modulates the pathogenic process of
      AD. tPA expression and activity developed around amyloid plaques in the brains of
      human amyloid precursor protein-overexpressing Tg2576 mice, which were weakened
      by the genetic ablation of tPA. Although the complete loss of tPA was
      developmentally fatal to Tg2576 mice, tPA-heterozygous Tg2576 mice expressed the
      more severe degenerative phenotypes than tPA wild-type Tg2576 mice, including
      abnormal and unhealthy growth, shorter life spans, significantly enhanced Abeta
      levels, and the deposition of more and larger amyloid plaques in the brain. In
      addition, the expression of synaptic function-associated proteins was
      significantly reduced, which in turn caused a more severe impairment in learning
      and memory performance in Tg2576 mice. Thus, endogenous tPA, preferentially its
      aggregate form, could degrade Abeta molecules and maintain low levels of brain
      Abeta, resulting in the delay of AD pathogenesis. 

PMID- 24126164
TI  - DNAJ mutations are rare in Chinese Parkinson's disease patients and controls.
AB  - Mutations in DNAJC13, DNAJC6 and DNAJC5 have been implicated in Parkinson's
      disease (PD). To determine if rare coding variants in these genes play a role in
      PD risk in the Chinese population, we sequenced all coding exons of the three
      genes in 99 early-onset PD cases and 99 controls, and genotyped 8 missense
      variants in another 711 PD cases and 539 controls. Besides two common missense
      variants that did not show association with PD, the remaining missense variants
      were extremely rare (<0.5%), found in healthy population controls and did not
      show enrichment in PD cases. Our results suggest that missense mutations in
      DNAJC13, DNAJC5 and DNAJC6 do not play a major role in PD in the Chinese
      population. 

PMID- 24126165
TI  - Liver metastases from breast cancer: Surgical resection or not? A case-matched
      control study in highly selected patients.
AB  - AIM: To determine whether, in a highly selected patient population, medical
      treatment combined with surgical resection of liver metastases from breast cancer
      is associated with improved survival compared with medical treatment alone.
      PATIENTS AND METHODS: Between 1988 and 2007, 100 liver resections for metastatic
      breast cancer were performed at Institut Curie, 51 of which met the criteria for
      inclusion in this case-control study. With the exception of bone metastases,
      patients with other distant metastasis sites were excluded. Surgery was only
      performed in patients with stable disease or disease responding to medical
      treatment evaluated by imaging evaluation. Surgical cases were individually
      matched with 51 patients receiving medical treatment only. All patients had 4 or
      fewer resectable liver metastases. The study group was matched with the control
      group for age, year of breast cancer diagnosis, time to metastasis, TNM stage,
      hormone receptor status and breast cancer tumour pathology. RESULTS: Univariate
      analysis confirmed a survival advantage for patients lacking bone metastases and
      axillary lymphadenopathy at the time of breast cancer diagnosis and for
      surgically treated patients. Multivariate analysis indicated that surgery and the
      absence of bone metastases were associated with a better prognosis. A
      multivariate Cox model adapted for paired data showed a RR = 3.04 (CI: 1.87-4.92)
      (p < 0.0001) in favour of surgical treatment. CONCLUSION: Surgical resection of
      liver metastases from primary breast cancer appears to provide a survival benefit
      for highly selected patients.

PMID- 24126166
TI  - Comment to the article: Salvage parenchymal liver transection for patients with
      insufficient volume increase after portal vein occlusion - an extension of the
      ALPPS approach.

PMID- 24126167
TI  - Deterrents to Nurses' Participation in Continuing Professional Development: an
      Integrative Literature Review.

PMID- 24126168
TI  - Association of alcohol consumption with incident hypertension among middle-aged
      and older Japanese population: the Ibarakai Prefectural Health Study (IPHS).
AB  - The objective of this study was to examine the effect of age on the relationship
      between alcohol consumption and incident hypertension in a general Japanese
      population. A cohort of Japanese men (n=37 310) and women (n=78 426) aged 40 to
      79 years who underwent community-based health checkups from 1993 to 2004 and were
      free of hypertension were followed up with annual examinations, including the
      measurement of blood pressure, until the end of 2010. Incident hypertension was
      defined as systolic blood pressure of >=140 mm Hg, diastolic blood pressure of
      >=90 mm Hg, or the initiation of treatment for hypertension. Hazard ratios for
      incident hypertension according to alcohol consumption were estimated using a Cox
      proportional hazards model adjusted for possible confounding variables. A total
      of 45 428 participants (39.3%) developed hypertension (16 155 men and 29 273
      women) for a mean follow-up time of 3.9 (1-18) years. Significant associations
      between alcohol consumption and incident hypertension were found in both sexes
      and age groups (P for trend was <0.001 for men aged 40-59 years and aged 60-79
      years; 0.004 for women aged 40-59 years and 0.026 for women aged 60-79 years). No
      significant interaction with age on the association of alcohol consumption with
      incident hypertension was found in either sex (P for interaction, >0.05). Our
      results suggest that alcohol consumption is a similar risk factor for incident
      hypertension in both the middle-aged and the older populations. 

PMID- 24126169
TI  - The impact of malaria in pregnancy on changes in blood pressure in children
      during their first year of life.
AB  - We established a maternal birth cohort in Ibadan, Nigeria, where malaria is
      hyperendemic, to assess how intrauterine exposure to malaria affected infant
      blood pressure (BP) development. In a local maternity hospital, healthy pregnant
      women had regular blood films for malaria parasites from booking to delivery.
      Growth and BP were measured on 318 babies, all followed from birth to 3 and 12
      months. Main outcomes were standardized measures of anthropometry and change in
      BP to 1 year. Babies exposed to maternal malaria were globally smaller at birth,
      and boys remained smaller at 3 months and 1 year. Change in systolic BP (SBP)
      during the year was greater in boys than in girls (20.9 versus 15.7 mm Hg;
      P=0.002) but greater in girls exposed to maternal malaria (18.7 versus 12.7 mm
      Hg; 95% confidence interval, 1-11 mm Hg; P=0.02). Eleven percent of boys (greater
      than twice than expected) had a SBP >=95th percentile (hypertensive, US
      criteria), of whom 68% had maternal malaria exposure. On regression analysis
      (beta coefficients, mm Hg), sex (boys>girls; beta=4.4; 95% confidence interval,
      1.1-7.7; P=0.01), maternal malaria exposure (3.64; 0.3-6.9; P=0.03), and weight
      change (2.4; 0.98-3.8/1 standard deviation score; P=0.001) all independently
      increased SBP change to 1 year, whereas increase in length decreased SBP (-1.98; 
      3.6 to -0.40). In conclusion, malaria-exposed boys had excess hypertension,
      whereas malaria-exposed girls a greater increase in SBP. Intrauterine exposure to
      malaria had sex-dependent effects on BP, independent of infant growth. Because
      infant-child-adult BP tracking is powerful, a malarial effect may contribute to
      the African burden of hypertension. 

PMID- 24126170
TI  - Childhood Blood Pressure Trends and Risk Factors for High Blood Pressure: The
      NHANES Experience 1988-2008.

PMID- 24126171
TI  - Williams syndrome predisposes to vascular stiffness modified by antihypertensive
      use and copy number changes in NCF1.
AB  - Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin,
      on human chromosome 7. Elastin insufficiency leads to the cardiovascular
      hallmarks of this condition, namely focal stenosis and hypertension.
      Extrapolation from the Eln(+/-) mouse suggests that affected people may also have
      stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac
      death. NCF1, one of the variably deleted Williams genes, is a component of the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is
      involved in the generation of oxidative stress, making it an interesting
      candidate modifier for vascular stiffness. Using a case-control design, vascular
      stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched
      controls. Cases had stiffer conducting vessels than controls (P<0.001), with
      increased stiffness observed in even the youngest children with Williams
      syndrome. Pulse wave velocity increased with age at comparable rates in cases and
      controls, and although the degree of vascular stiffness varied, it was seen in
      both hypertensive and normotensive Williams participants. Use of antihypertensive
      medication and extension of the Williams deletion to include NCF1 were associated
      with protection from vascular stiffness. These findings demonstrate that vascular
      stiffness is a primary vascular phenotype in Williams syndrome and that treatment
      with antihypertensives or agents inhibiting oxidative stress may be important in
      managing patients with this condition, potentially even those who are not overtly
      hypertensive. 

PMID- 24126172
TI  - Opposite predictive value of pulse pressure and aortic pulse wave velocity on
      heart failure with reduced left ventricular ejection fraction: insights from an
      Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival
      Study (EPHESUS) substudy.
AB  - Although hypertension contributes significantly to worsen cardiovascular risk,
      blood pressure increment in subjects with heart failure is paradoxically
      associated with lower risk. The objective was to determine whether pulse pressure
      and pulse wave velocity (PWV) remain prognostic markers, independent of treatment
      in heart failure with reduced left ventricular function. The investigation
      involved 6632 patients of the Eplerenone Post-Acute Myocardial Infarction Heart
      Failure Efficacy and Survival Study. All subjects had acute myocardial infarction
      with left ventricular ejection fraction <40% and signs/symptoms of heart failure.
      Carotid-femoral PWV was measured in a subpopulation of 306 subjects. In the
      overall population, baseline mean arterial pressure <90 mm Hg was associated with
      higher all-cause death (hazard ratio, 1.14 [95% confidence interval, 1.00-1.30];
      P<0.05), whereas higher left ventricular ejection fraction or pulse pressure was
      associated with lower rates of all-cause death, cardiovascular
      death/hospitalization, and cardiovascular death. In the subpopulation, increased
      baseline PWV was associated with worse outcomes (all-cause death: 1.16 [1.03
      1.30]; P<0.05 and cardiovascular deaths: 1.16 [1.03-1.31]; P<0.05), independent
      of age and left ventricular ejection fraction. Using multiple regression
      analysis, systolic blood pressure and age were the main independent factors
      positively associated with pulse pressure or PWV, both in the entire population
      or in the PWV substudy. In heart failure and low ejection fraction, our results
      suggest that pulse pressure, being negatively associated with outcome, is more
      dependent on left ventricular function and thereby no longer a marker of aortic
      elasticity. In contrast, increased aortic stiffness, assessed by PWV, contributes
      significantly to cardiovascular death. 

PMID- 24126173
TI  - Myocardial mineralocorticoid receptor activation by stretching and its functional
      consequences.
AB  - Myocardial stretch triggers an angiotensin II-dependent autocrine/paracrine loop
      of intracellular signals, leading to reactive oxygen species-mediated activation
      of redox-sensitive kinases. Based on pharmacological strategies, we previously
      proposed that mineralocorticoid receptor (MR) is necessary for this stretch
      triggered mechanism. Now, we aimed to test the role of MR after stretch by using
      a molecular approach to avoid secondary effects of pharmacological MR blockers.
      Small hairpin interference RNA capable of specifically knocking down the MR was
      incorporated into a lentiviral vector (l-shMR) and injected into the left
      ventricular wall of Wistar rats. The same vector but expressing a nonsilencing
      sequence (scramble) was used as control. Lentivirus propagation through the left
      ventricle was evidenced by confocal microscopy. Myocardial MR expression, stretch
      triggered activation of redox-sensitive kinases (ERK1/2-p90(RSK)), the consequent
      Na(+)/H(+) exchanger-mediated changes in pHi (HEPES-buffer), and its mechanical
      counterpart, the slow force response, were evaluated. Furthermore, reactive
      oxygen species production in response to a low concentration of angiotensin II
      (1.0 nmol/L) or an equipotent concentration of epidermal growth factor (0.1
      MUg/mL) was compared in myocardial tissue slices from both groups. Compared with
      scramble, animals transduced with l-shMR showed (1) reduced cardiac MR
      expression, (2) cancellation of angiotensin II-induced reactive oxygen species
      production but preservation of epidermal growth factor-induced reactive oxygen
      species production, (3) cancellation of stretch-triggered increase in ERK1/2
      p90(RSK) phosphorylation, (4) lack of stretch-induced Na(+)/H(+) exchanger
      activation, and (5) abolishment of the slow force response. Our results provide
      strong evidence that MR activation occurs after myocardial stretch and is a key
      factor to promote redox-sensitive kinase activation and their downstream
      consequences. 

PMID- 24126174
TI  - Reference values and factors associated with renal resistive index in a family
      based population study.
AB  - Increased renal resistive index (RRI) has been recently associated with target
      organ damage and cardiovascular or renal outcomes in patients with hypertension
      and diabetes mellitus. However, reference values in the general population and
      information on familial aggregation are largely lacking. We determined the
      distribution of RRI, associated factors, and heritability in a population-based
      study. Families of European ancestry were randomly selected in 3 Swiss cities.
      Anthropometric parameters and cardiovascular risk factors were assessed. A renal
      Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of
      both kidneys. We used multilevel linear regression analysis to explore the
      factors associated with RRI, adjusting for center and family relationships. Sex
      specific reference values for RRI were generated according to age. Heritability
      was estimated by variance components using the ASSOC program (SAGE software).
      Four hundred women (mean age+/-SD, 44.9+/-16.7 years) and 326 men (42.1+/-16.8
      years) with normal renal ultrasound had mean RRI of 0.64+/-0.05 and 0.62+/-0.05,
      respectively (P<0.001). In multivariable analyses, RRI was positively associated
      with female sex, age, systolic blood pressure, and body mass index. We observed
      an inverse correlation with diastolic blood pressure and heart rate. Age had a
      nonlinear association with RRI. We found no independent association of RRI with
      diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or
      estimated glomerular filtration rate. The adjusted heritability estimate was 42+/
      8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI
      normal values depend on sex, age, blood pressure, heart rate, and body mass
      index. The significant heritability of RRI suggests that genes influence this
      phenotype. 

PMID- 24126175
TI  - High blood pressure after acute ischemic stroke is associated with poor clinical
      outcomes: Fukuoka Stroke Registry.
AB  - The relationship between the poststroke blood pressure (BP) and functional
      outcomes in patients with acute ischemic stroke is still controversial. The aim
      of the present study was to elucidate the impact of the poststroke BP on the
      clinical outcomes of acute ischemic stroke. Among the patients in the Fukuoka
      Stroke Registry, 1874 patients with first-ever acute ischemic stroke (within 24
      hours of onset) who had been functionally independent before onset were
      prospectively enrolled in the present study. The poststroke BP levels were
      defined as the average values during the 48 hours after onset. The study outcomes
      were a good neurological recovery, neurological deterioration, and a poor
      functional outcome. The higher poststroke BP levels were significantly associated
      with a lower probability of a good neurological recovery and elevated risks of
      neurological deterioration and a poor functional outcome after adjusting for
      potential confounding factors. The multivariate-adjusted odds ratios (95%
      confidence interval) in the highest quintile of systolic BP (versus the lowest
      quintile as a reference) were 0.51 (0.37-0.71) for a good neurological recovery,
      1.92 (1.15-3.27) for neurological deterioration, and 2.51 (1.69-3.74) for a poor
      functional outcome. Similar associations were observed when we applied the
      poststroke diastolic BP or pulse pressure. No evidence of the J-curve phenomenon
      was observed for each association. These results suggest that a high poststroke
      BP was significantly associated with unfavorable clinical outcomes in patients
      with acute ischemic stroke. There was no evidence of the J-curve phenomenon
      between the poststroke BP levels and the clinical outcomes. 

PMID- 24126176
TI  - Equilibrium enzymes in regulatory systems: a problem in scalar-vector transition.

PMID- 24126177
TI  - Hypertension and children: should we be aware?

PMID- 24126178
TI  - Potent antihypertensive action of dietary flaxseed in hypertensive patients.
AB  - Flaxseed contains omega-3 fatty acids, lignans, and fiber that together may
      provide benefits to patients with cardiovascular disease. Animal work identified
      that patients with peripheral artery disease may particularly benefit from
      dietary supplementation with flaxseed. Hypertension is commonly associated with
      peripheral artery disease. The purpose of the study was to examine the effects of
      daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP)
      in peripheral artery disease patients. In this prospective, double-blinded,
      placebo-controlled, randomized trial, patients (110 in total) ingested a variety
      of foods that contained 30 g of milled flaxseed or placebo each day over 6
      months. Plasma levels of the omega-3 fatty acid alpha-linolenic acid and
      enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not
      increase significantly in the placebo group. Patient body weights were not
      significantly different between the 2 groups at any time. SBP was ~ 10 mm Hg
      lower, and DBP was ~ 7 mm Hg lower in the flaxseed group compared with placebo
      after 6 months. Patients who entered the trial with a SBP >= 140 mm Hg at
      baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP
      from flaxseed ingestion. The antihypertensive effect was achieved selectively in
      hypertensive patients. Circulating alpha-linolenic acid levels correlated with
      SBP and DBP, and lignan levels correlated with changes in DBP. In summary,
      flaxseed induced one of the most potent antihypertensive effects achieved by a
      dietary intervention.

PMID- 24126179
TI  - Resistance artery creatine kinase mRNA and blood pressure in humans.
AB  - Hypertension remains the main risk factor for cardiovascular death. Environmental
      and biological factors are known to contribute to the condition, and circulating
      creatine kinase was reported to be the main predictor of blood pressure in the
      general population. This was proposed to be because of high resistance artery
      creatine kinase-BB rapidly regenerating ATP for vascular contractility.
      Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human
      resistance arteries are associated with blood pressure. We isolated resistance
      sized arteries from omental fat donated by consecutive women undergoing uterine
      fibroid surgery. Blood pressure was measured in the sitting position. Vessels of
      13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years
      (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm
      Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative
      real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy
      numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect
      correlation with diastolic blood pressure (correlation coefficient, 0.9; 95%
      confidence interval, 0.6-1.0) and were well correlated with systolic blood
      pressure, with a 90% relative increase in resistance artery creatine kinase B
      mRNA in hypertensives compared with normotensives, normalized copy numbers were,
      respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge,
      this is the first direct evidence suggesting that resistance artery creatine
      kinase mRNA expression levels concur with blood pressure levels, almost doubling
      with hypertension. These findings add to the evidence that creatine kinase might
      be involved in the vasculature's pressor responses. 

PMID- 24126180
TI  - Intracoronary infusion of mononuclear bone marrow-derived stem cells is
      associated with a lower plaque burden after four years.
AB  - AIM: To assess the long-term effects of intracoronary stem cell (SC) infusion
      following acute myocardial infarction (AMI) on the local atherosclerotic process
      at the site of infusion after four years of follow-up. METHODS: We evaluated 18
      post-AMI patients. Group 1 consisted of nine patients given an intracoronary
      injection of autologous mononuclear SC, and group 2 consisted of nine patients
      given a placebo injection. The plaque count, plaque burden (PB) and coronary
      calcium score (CCS) were assessed using multislice 64 CT angiography of the
      coronary tree four years after SC injection. RESULTS: The total PB and CCS along
      the entire coronary segment distal to the site of infusion were significantly
      lower in the SC group (PB-702 mm(3) vs. 1.465 mm(3), p=0.0006; CCS-295 vs. 796,
      p< 0.0001).The mean PB per coronary artery was 112.12 mm(3)+/-16.82 mm(3) for the
      treated arteries vs. 189.56 mm(3)+/-20.98 mm(3) for the untreated arteries
      (p<0.0001), while the mean CCS was 53.12+/-16.4 vs. 106.43+/-10.86 (p<0.0001). In
      the SC group, there were significant differences in the mean PB (87.75 mm(3) vs.
      112.12 mm(2), p= 0.005) and mean CCS (36.87 vs. 53.12, p=0.04) between the
      coronary segment infused with SC and the entire coronary artery. CONCLUSIONS:
      Multislice CT angiography of atheromatous plaques in the coronary tree four years
      after SC infusion in post-AMI patients indicates a significantly lower
      atheromatous plaque burden, as demonstrated by a lower plaque volume and lower
      CCS at the site of stem cell infusion compared with other coronary territories.

PMID- 24126182
TI  - Mucocutaneous leishmaniasis as presentation of HIV infection in Sardinia, insular
      Italy.
AB  - Leishmaniasis is endemic in Sardinia but only cutaneous and visceral cases have
      been reported to date. We report a case of mucocutaneous leishmaniasis as
      presentation of HIV infection in a Sardinian patient who had never visited
      endemic areas. Serological and clinical diagnosis was cytologically and
      histopathologically confirmed. The patient had a good response to treatment with
      liposomal amphotericin combined with highly active antiretroviral therapy without
      recurrences after four years. Our case report highlights the need to better
      assess the circulation of species, risk factors and clinical spectrum of
      Leishmania infection in the Italian Mediterranean islands. 

PMID- 24126181
TI  - Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A
      and cannabinoid CB1 receptors in adolescent BTBR mice.
AB  - Hypothalamic pituitary adrenal (HPA) axis responses to change and social
      challenges during adolescence can influence mental health and behavior into
      adulthood. To examine how HPA tone in adolescence may contribute to
      psychopathology, we challenged male adolescent (5 weeks) and adult (16 weeks)
      BTBR T(+)tf/J (BTBR) and 129S1/SvImJ (129S) mice with novelty in sociability
      tests. In prior studies these strains had exaggerated or altered HPA stress
      responses and low sociability relative to C57BL/6J mice in adulthood. In
      adolescence these strains already exhibited similar or worse sociability deficits
      than adults or age-matched C57 mice. Yet BTBR adolescents were less hyperactive
      and buried fewer marbles than adults. Novelty-induced corticosterone (CORT)
      spikes in adolescent BTBR were double adult levels, and higher than 129S or C57
      mice at either age. Due to their established role in HPA feedback, we
      hypothesized that hippocampal Galphai/o-coupled serotonin 5-HT1A and cannabinoid
      CB1 receptor function might be upregulated in BTBR mice. Adolescent BTBR mice had
      higher hippocampal 5-HT1A density as measured by [(3)H] 8-hydroxy-2-(di-n
      propylamino) tetralin (8-OH-DPAT) binding than C57 mice, and adult BTBR 8-OH-DPAT
      stimulated GTPgammaS binding was higher than in either C57 or 129S mice in this
      region. Further, BTBR hippocampal CB1 density measured by [(3)H]CP55,940 binding
      was 15-20% higher than in C57. CP55,940-stimulated GTPgammaS binding in adult
      BTBR dentate gyrus was 30% higher then 129S (p<0.05), but was not a product of
      greater neuronal or cell density defined by NeuN and DAPI staining. Hence
      hyperactive HPA responsiveness during adolescence may underlie 5-HT1A and CB1
      receptor up-regulation and behavioral phenotype of BTBR mice.

PMID- 24126183
TI  - [Advances in head and neck cancers on behalf of the French Intergroup ORL and
      GORTEC].
AB  - Head and neck cancers are the fifth among the most common cancers in France. Two
      thirds of cases occur at an advanced stage. For advanced disease, progression
      free survival, despite undeniable progress, remains below 50% at three years. The
      last 20 years have been marked by the necessity to identify situations where less
      intense surgery and/or radiotherapy and/or chemotherapy is possible without
      jeopardizing the prognosis, and situations where a therapeutic intensification is
      necessary and results in a gain in survival while better preserving function with
      less toxicity. French cooperative groups gathering radiation oncologists
      (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the
      management of systemic treatments in head and neck cancers (GERCOR) are now
      belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head
      and neck cancers.

PMID- 24126184
TI  - How to address the sample preparation of hydrophilic compounds: Determination of
      entecavir in plasma and plasma ultrafiltrate with novel extraction sorbents.
AB  - Two fast, simple, selective and economical sample preparation methods for the
      determination of entecavir in biological materials available at low amounts are
      reported. The choice of optimal extraction techniques was performed with regard
      to analyte hydrophilicity, sample volumes, selectivity, method recovery and
      rapidity. The compatibility of the eluate with the hydrophilic interaction
      chromatography (HILIC) mobile phase was crucial to allow the elimination of the
      evaporation and reconstitution steps and to obtain acceptable peak shapes.
      Different types of sorbents were employed for the extraction of two biological
      materials (plasma and plasma ultrafiltrate). The mixed-mode polymeric sorbent MCX
      was chosen as a suitable one for the solid phase extraction (SPE) of plasma
      samples. The analytes were eluted with 1ml of the mixture of 5 % ammonium
      hydroxide in ACN:water (95:5). Protein precipitation (PP) with 1ml of ACN was
      used to remove proteins from 500MUl of plasma sample prior to SPE extraction. The
      microextraction by packed sorbent (MEPS) was employed for the cleaning up of
      plasma ultrafiltrate samples due to very small volumes available for the
      analysis. MEPS implemented a novel sorbent based on porous graphitic carbon, semi
      automatic analytical syringe and a small volume of sample (50MUl). The elution
      step was performed using 100MUl of the mixture of 5mM ammonium acetate pH 4.0:ACN
      (25:75). The MEPS eluate was fully compatible with HILIC mobile phase
      subsequently used for the analysis of entecavir, unlike SPE eluate, which had to
      be evaporated and reconstituted in mobile phase. Both analytical methods were
      validated and demonstrated good linearity in a range 1-100ng/ml (r(2)>0.9992) for
      plasma samples and in a range 0.5-100ng/ml (0.9991) for the plasma ultrafiltrate
      samples. Intra-day accuracy expressed as recovery was within the range from 80
      98% for the plasma samples and 97-106% for the plasma ultrafiltrate samples.
      Inter-day accuracy ranged within 81-106% for the plasma and 95-101% for the
      plasma ultrafiltrate samples. The intra-day precision expressed as the % of RSD
      was lower than 4% for both matrices and inter-day precision was lower than 7% for
      plasma and lower than 17% for plasma ultrafiltrate. Method sensitivity reached
      LLOQ of 1ng/ml in plasma and 0.5ng/ml in plasma ultrafiltrate samples. The method
      was applied for the determination of concentration-time profiles of entecavir in
      plasma of the perfusate for rat kidney perfusion and for the measurement of
      concentration of entecavir in plasma ultrafiltrate samples. The results should be
      helpful in the evaluation of excretion mechanism of entecavir. 

PMID- 24126185
TI  - GCN2-like eIF2alpha kinase manages the amino acid starvation response in
      Toxoplasma gondii.
AB  - The apicomplexan protozoan Toxoplasma gondii is a significant human and
      veterinary pathogen. As an obligate intracellular parasite, Toxoplasma depends on
      nutrients provided by the host cell and needs to adapt to limitations in
      available resources. In mammalian cells, translational regulation via GCN2
      phosphorylation of the alpha subunit of eukaryotic translation initiation factor
      2 (eIF2alpha) is a key mechanism for adapting to nutrient stress. Toxoplasma
      encodes two GCN2-like protein kinases, TgIF2K-C and TgIF2K-D. We previously
      showed that TgIF2K-D phosphorylates T. gondii eIF2alpha (TgIF2alpha) upon egress
      from the host cell, which enables the parasite to overcome exposure to the
      extracellular environment. However, the function of TgIF2K-C remained unresolved.
      To determine the functions of TgIF2K-C in the parasite, we cloned the cDNA
      encoding TgIF2K-C and generated knockout parasites of this TgIF2alpha kinase to
      study its function during the lytic cycle. The TgIF2K-C knockout did not exhibit
      a fitness defect compared with parental parasites. However, upon infection of
      human fibroblasts that were subsequently cultured in glutamine-free medium, the
      intracellular TgIF2K-C knockout parasites were impeded for induced
      phosphorylation of TgIF2alpha and showed a 50% reduction in the number of plaques
      formed compared with parental parasites. Furthermore, we found that this growth
      defect in glutamine-free media was phenocopied in parasites expressing only a non
      phosphorylatable TgIF2alpha (TgIF2alpha-S71A), but not in a TgIF2K-D knockout.
      These studies suggest that Toxoplasma GCN2-like kinases TgIF2K-C and TgIF2K-D
      evolved to have distinct roles in adapting to changes in the parasite's
      environment. 

PMID- 24126186
TI  - Population genetic characterisation of dominant Cryptosporidium parvum subtype
      IIaA15G2R1.
AB  - The subtype IIaA15G2R1 at the 60 kDa glycoprotein (gp60) gene locus is the most
      dominant Cryptosporidium parvum infecting dairy cattle and humans in
      industrialised nations. The reasons for its high transmissibility are not clear,
      and it remains to be determined whether this subtype represents a homogeneous
      parasite population. In this study, we sequence-characterised 26 IIaA15G2R
      subtype specimens and 26 non-IIaA15G2R subtype specimens from the United States,
      Canada, United Kingdom and Spain at seven other known polymorphic loci, including
      CP47, CP56, DZ-HRGP, MSC6-5, MSC6-7, RPGR and ZPT. Extensive heterogeneity within
      IIaA15G2R1 and discordance in typing results between gp60 and other genetic
      markers were observed. Results of inter-locus and intra-ZPT linkage
      disequilibrium and recombination analyses indicated that the heterogeneity within
      IIaA15G2R1 and discordance in typing results among genetic loci were largely due
      to the occurrence of genetic recombination, mostly within the gp60 subtype
      IIaA15G2R1. Although there was no clear population diversion between IIaA15G2R
      and non-IIaA15G2R subtypes, results of STRUCTURE and FST analyses suggested the
      presence of at least two subpopulations; subpopulation 1 had an epidemic
      population structure and was widely distributed, whereas subpopulation 2 had a
      clonal population structure and consisted of geographically segregated multilocus
      subtypes. Genetic recombination between epidemic and geographically segregated C.
      parvum populations appeared to be a driving force in the emergence of a hyper
      transmissible IIaA15G2R1 subtype. Genetic recombination was observed even between
      the zoonotic IIa subtype family and anthroponotic subtype family IIc at CP56,
      MSC6-7 and ZPT. Thus, the IIaA15G2R1 subtype at gp60 is likely a fitness marker
      for C. parvum and the wide spread of IIaA15G2R1 subtype around the world is
      probably independent of the sequence characteristics at other genetic loci.

PMID- 24126187
TI  - A multi-dimensional approach to insight and its evolution in first-episode
      psychosis: a 1-year outcome naturalistic study.
AB  - The aim of the study was to describe the evolution of the different dimensions of
      insight at 1 year and its associations with psychopathology and symptomatic
      remission. Participants included 55 patients hospitalized for a first psychosis
      episode and followed up at 6 and 12 months after discharge. Measures included the
      Scale to Assess Unawareness of Mental Disorder and the Positive and Negative
      Syndrome Scale (PANSS). Six dimensions of insight were evaluated, for current
      episode at hospital discharge and at 6 and 12 month FUs and past episode (at 6
      and 12 month follow-ups). Our results show that concerning the current episode,
      only awareness of the social consequences and of the positive symptoms
      significantly improved during follow-up. Insight into the past episode improved
      for awareness of having a mental disorder, the social consequences and the
      positive symptoms of mental illness. Cross-sectional associations between insight
      and PANSS show weak to moderate, albeit significant, associations. Most of the
      dimensions of insight are positively and significantly associated with remission.
      Our findings suggest that the main underlying dimensions of insight evolve
      differently over time, which could suggest different inherent processes. This
      could be useful for developing psychotherapeutic programmes acting upon the
      different aspects of insight. 

PMID- 24126188
TI  - An ecologically valid performance-based social functioning assessment battery for
      schizophrenia.
AB  - Psychiatrists pay more attention to the social functioning outcome of
      schizophrenia nowadays. How to evaluate the real world function among
      schizophrenia is a challenging task due to culture difference, there is no such
      kind of instrument in terms of the Chinese setting. This study aimed to report
      the validation of an ecologically valid performance-based everyday functioning
      assessment for schizophrenia, namely the Beijing Performance-based Functional
      Ecological Test (BJ-PERFECT). Fifty community-dwelling adults with schizophrenia
      and 37 healthy controls were recruited. Fifteen of the healthy controls were re
      tested one week later. All participants were administered the University of
      California, San Diego, Performance-based Skill Assessment-Brief version (UPSA-B)
      and the MATRICS Consensus Cognitive Battery (MCCB). The finalized assessment
      included three subdomains: transportation, financial management and work ability.
      The test-retest and inter-rater reliabilities were good. The total score
      significantly correlated with the UPSA-B. The performance of individuals with
      schizophrenia was significantly more impaired than healthy controls, especially
      in the domain of work ability. Among individuals with schizophrenia, functional
      outcome was influenced by premorbid functioning, negative symptoms and
      neurocognition such as processing speed, visual learning and attention/vigilance.

PMID- 24126189
TI  - No association of endocannabinoid genes with bipolar disorder or lithium response
      in a Sardinian sample.
AB  - Bipolar disorder (BD) is a chronic and severe psychiatric condition with an
      underlying component of genetic susceptibility. Mounting evidence suggests a
      potential role of the endogenous cannabinoid (eCB) system in the pathogenesis of
      BD. Here we investigated the role of genes encoding for key eCB elements on the
      risk of developing BD in a sample of 357BD patients and 422 healthy controls of
      Sardinian ancestry. Using the HapMap CEU population SNP database, we selected 25
      tag Single Nucleotide Polymorphisms (tSNPs) in N-acyl phosphatidylethanolamine
      phospholipase D (NAPE-PLD), cannabinoid receptor 1 (CNR1) and fatty acid amide
      hydrolase (FAAH) genes. No significant association was reported for FAAH or CNR1.
      SNPs rs11487077 and rs6465903 in NAPE-PLD showed nominal association (p=0.033 and
      p=0.026, respectively) with BD, not significant after permutation testing. These
      SNPs were also tested for association with lithium response in 204 BD patients
      characterized for response to long-term lithium treatment, reporting no
      significant findings. As a whole, our results do not support a clear role of
      FAAH, CNR1 and NAPE-PLD in BD and lithium response. Additional studies on
      independent, larger samples are warranted to further explore the involvement of
      the eCB system in BD. 

PMID- 24126190
TI  - Carbamazepine-exposure during gestation and lactation affects pubertal onset and
      spermatic parameters in male pubertal offspring.
AB  - Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells,
      affecting steroidogenesis and causes fetal malformation. The aim of this study
      was to investigate the effects of CBZ on male sexual maturation and other male
      parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding.
      The anogenital distance (AGD) and the anogenital index (AGI) were obtained.
      Testicular descent and preputial separation were also evaluated. The offspring
      was euthanized at PND 41 and 63. The accessory glands were weighed and the testes
      were collected for histopathological, morphometric and sterological analyses. The
      numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an
      increase of AGI and a delay of testicular descent and of preputial separation.
      CBZ also caused a decrease of testosterone level and of sperm count and an
      increase of abnormal sperm. These results indicate that CBZ delays puberty onset
      and affects steroidogenesis and sperm quality. 

PMID- 24126191
TI  - [Medicine supplies in developing countries: saving public medicine procurement
      bodies in Africa].
AB  - What is the future for public medicine procurement bodies in Africa? Who wants
      them to survive? Who wants them to die? Do we want pharmaceutical businesses or
      logistic platforms? 

PMID- 24126192
TI  - Effect of deep brain stimulation on levodopa-induced dyskinesias and striatal
      oscillatory local field potentials in a rat model of Parkinson's disease.
AB  - BACKGROUND: In Parkinson's disease (PD) dyskinesias appear after long-term
      dopaminergic treatment. Deep brain stimulation (DBS) of the subthalamic nucleus
      (STN) or the globus pallidus internus (GPi) is a well-established treatment
      option for both PD symptoms and complications of medication. OBJECTIVE: To
      elucidate physiological mechanisms of the effect of DBS on levodopa-induced
      dyskinesias (LID) we investigated both DBS in the GPi and the centromedian
      parafascicular complex (CM-Pf), which are part of an internal basal ganglia loop
      connecting with the dorsolateral striatum. In particular, we focused on changes
      of oscillatory activity in the dorsolateral striatum, which also presents the
      entrance region of the basal ganglia (BG). METHODS: 6-Hydroxydopamine (6-OHDA)
      hemiparkinsonian (HP) rats and 6-OHDA lesioned HP rats with LID (HP-LID) were
      used to compare the effect of DBS in the entopeduncular nucleus (EPN, the
      equivalent to the human GPi) and the thalamic parafascicular nucleus (Pf, the
      equivalent of the human CM-Pf) on dyskinesias and neuronal oscillatory activity
      of selected frequency bands in the dorsolateral striatum on and off levodopa.
      RESULTS: In HP-LID rats the relative beta and gamma power was lower, while
      relative theta power was higher as compared to HP rats. Chronic DBS of either the
      EPN or the Pf improved dyskinesia scores in HP-LID rats, and no differences in
      oscillatory activity were observed between groups. CONCLUSIONS: Stimulation of
      the Pf has a specific impact on dyskinesias, which is similar to that found after
      EPN stimulation, and which is accompanied by changes of oscillatory activity.

PMID- 24126193
TI  - Active surveillance for small renal masses diagnosed in elderly or comorbid
      patients: looking for the best treatment strategy.
AB  - INTRODUCTION: Aim of this study is to provide our results after long-term active
      surveillance (AS) protocol for small renal masses (SRMs), and to report the
      outcomes of patients who remained in AS compared to those who underwent delayed
      surgical intervention. PATIENTS AND METHODS: We retrospectively reviewed our
      database of 58 patients diagnosed with 60 contrast enhancing SRMs suspicious for
      renal cell carcinoma (RCC). All patients had clinical and radiological follow-up
      every 6 months. We evaluated the differences between patients who remained on AS
      and those who underwent surgical delayed intervention. RESULTS: The mean age was
      75 years, the mean follow-up was 88.5 months. The median initial tumor size at
      presentation was 2.6cm, and the median estimated tumor volume was 8.7cm(3). The
      median linear growth rate of the cohort was 0.7cm/year, and the median volumetric
      growth rate was 8.8 cm(3)/year. Death for metastatic disease occurred in 2
      patients (3.4%). No correlation was found between initial tumor size and size
      growth rate. The mean linear and volumetric growth rates of the group of patients
      who underwent surgery was higher than in those who remained on surveillance (1.9
      vs. 0.4cm/year and 16.1 vs. 4.6 cm(3)/year, respectively; P<.001). CONCLUSIONS:
      Most of SRMs demonstrate to have an indolent course and low metastatic potential.
      Malignant disease could have faster linear and volumetric growth rates, thus
      suggesting the need for a delayed surgical intervention. In properly selected
      patients with low life-expectancy, AS could be a reasonable option in the
      management of SRMs.

PMID- 24126195
TI  - Laparoscopic cystectomy and intracorporeal continent urinary diversion (Mainz II)
      in treatment for interstitial cystitis.
AB  - INTRODUCTION: Interstitial cystitis (IC) is a difficult-to-manage chronic and
      insidious condition. We present a series of patients with IC who failed to
      respond to conservative treatment. The patients underwent total cystectomy with
      completely intracorporeally performed continent urinary diversion (Mainz II
      rectosigmoid pouch) as a radical alternative to the treatment of this condition.
      MATERIAL AND METHODS: Eight patients who fulfilled the clinical criteria for IC
      according to the National Institute of Health and in whom all previous
      conservative treatments had failed between January 2001 and April 2009 were
      operated on. A descriptive analysis was made with the following variables: age,
      surgical risk according to the American Society of Anesthesiology (ASA), total
      surgical time (ST), ST of the cystectomy, ST of the urinary diversion, early and
      late complications, time of hospital stay, bleeding and need of transfusion,
      specimen extraction pathway and uterine sparing. RESULTS: Mean age was 54.25 (+/
      17.8) years, total mean ST 286.4 (+/-44.8) minutes, mean ST of the cystectomy
      86.2 (+/-25.6) minutes, mean ST of the diversion 123.7 (+/-28.6) minutes, mean
      bleeding 321.4 (+/-242.9) cc, mean time of hospital stay 8.3 (+/-1.3) days. Fifty
      percent were ASA I, 37.5% ASA II and 12.5% ASA III. A hysterectomy was made in
      50% of the cases. In 5 cases (62.5%) the bladder was extracted through the rectum
      and in 3 cases (37.5%) through the vagina. The only early complication was
      urinary sepsis in one patient. There was no conversion in the series.
      CONCLUSIONS: Total cystectomy with urethrectomy and intracorporeal continent
      urinary diversion is an effective and definitive alternative for the treatment of
      treatment resistant IC. Their technical difficulty and its learning curve limit
      their application to centers with an extensive experience in laparoscopy.

PMID- 24126194
TI  - Bladder changes after several coverage modalities in the surgically induced model
      of myelomeningocele in lambs.
AB  - OBJECTIVE: To assess the presence of early bladder abnormalities in a prenatally
      corrected and uncorrected animal model of Myelomeningocele (MMC). METHOD: A MMC
      like lesion was surgically created in 18 fetal lambs between the 60th and the
      80th day of gestation. Eight of them did not undergo fetal repair (group A),
      three were repaired with an open two-layer closure (group B), three using
      BioGlue(r) (groupC) and four fetoscopically (group D). At term, bladders were
      examined macroscopically and histopathological changes were assessed using H-E
      and Masson Trichrome. RESULTS: Five animals in group A (5/8, 62%), two in group B
      (2/3, 66%), one in group C (1/3, 33%) and one in group D (1/4, 25%) survived.
      Macroscopically bladders in group A were severely dilated and showed thinner
      walls. Microscopically they showed a thin layer of colagenous tissue (Blue layer.
      BL) lying immediately subjacent to the urothelium. The muscular layers were
      thinner. Non compliant pattern with thick wall and low capacity was also found in
      the non corrected model. Group B and the control showed preservation of muscular
      layers and absence of BL. Groups C and D presented BL but also preservation of
      muscular layers. CONCLUSION: Bladder changes in a surgically-induced model of MMC
      can be described using histopathological data. Both extremes of bladder changes
      can be observed in the model. These changes were completely prevented with open
      fetal surgery and partially with other coverage modalities.

PMID- 24126196
TI  - Synthetic biology: evolution or revolution? A co-founder's perspective.
AB  - In this article, we relate the story of Synthetic Biology's birth, from the
      perspective of a co-founder, and consider its original premise--that
      standardization and abstraction of biological components will unlock the full
      potential of biological engineering. The standardization ideas of Synthetic
      Biology emerged in the late 1990s from a convergence of research on cellular
      computing, and were motivated by an array of applications from tissue
      regeneration to bio-sensing to mathematical programming. As the definition of
      Synthetic Biology has grown to be synonymous with Biological Engineering and
      Biotechnology, the field has lost sight of the fact that its founding premise has
      not yet been validated. While the value of standardization has been proven in
      many other engineering disciplines, none of them involve self-replicating
      systems. The engineering of self-replicating systems will likely benefit from
      standardization, and also by embracing the forces of evolution that inexorably
      shape such systems.

PMID- 24126197
TI  - Guidelines for perioperative haemodynamic optimization.

PMID- 24126198
TI  - Comparing methods to secure external fetal-monitoring devices.
AB  - PURPOSE: To compare two methods of securing external uterine tocodynamometer and
      fetal heart rate (FHR) ultrasound monitors to the abdomen. STUDY DESIGN AND
      METHODS: 100 women were enrolled in a prospective, randomized trial comparing the
      adhesive patch method to the circumferential belt method for securing electronic
      fetal monitoring (EFM) devices during labor. Device efficacies were compared by
      evaluating the EFM time lost due to monitor malpositioning. Investigator
      developed nurse and patient questionnaires were used to assess satisfaction with
      each device. RESULTS: Data from 94 patients and 21 nurses were analyzed. There
      was no significant difference in efficacy between the two devices. There was a
      significant preference for the adhesive patch method in the nurses' assessment of
      EFM positioning, continuous assessment during epidural, and assessment during
      labor and birth, and in the patients' assessment of their mobility and comfort.
      This suggests that the adhesive patch method is equivalent to the circumferential
      method in its primary purpose (its ability to effectively position the EFM
      devices) and preferable over the circumferential method in terms of nurse and
      patient satisfaction. CLINICAL IMPLICATIONS: The adhesive patch method of
      securing fetal-monitoring devices could be welcomed as a suitable alternate to
      the circumferential belt method during labor.

PMID- 24126199
TI  - Association between smoking and p53 mutation in lung cancer: a meta-analysis.
AB  - AIMS: To carry out a meta-analysis on the relationship between smoking and p53
      gene mutation in lung cancer patients. MATERIALS AND METHODS: PubMed, Web of
      Science, ProQest and Medline were searched by using the key words: 'lung cancer
      or lung neoplasm or lung carcinoma', 'p53 mutation' and 'smoking'. According to
      the selection criteria, 15 articles were identified and methodologically analysed
      by stata 12.0 software package. Crude odds ratios with 95% confidence intervals
      calculated using the fixed-effects model were used to assess the strength of
      association between smoking and p53 mutation in lung cancer. RESULTS: In total,
      15 articles with 1770 lung cancer patients were identified; 69.6% of the patients
      were smokers, 30.4% were non-smokers. Overall, smokers with lung cancer had a
      2.70-fold (95% confidence interval 2.04-3.59) higher risk for mutation than the
      non-smokers with lung cancer. In subgroup analyses, the increased risk of p53
      mutation in smokers than in non-smokers was found in the non-small cell lung
      cancer (NSCLC) group (odds ratio = 2.38, 95% confidence interval = 1.71-3.32) and
      in the NSCLC and SCLC group (odds ratio = 3.82, 95% confidence interval = 2.19
      6.69). CONCLUSIONS: This meta-analysis strongly suggests that p53 mutation is
      associated with smoking-induced lung cancer. Smokers with lung cancer had a
      higher risk for p53 mutation than non-smokers.

PMID- 24126200
TI  - Molecular characterization and population structure of blackberry vein banding
      associated virus, new Ampelovirus associated with yellow vein disease.
AB  - Blackberry yellow vein disease is the most important viral disease of blackberry
      in the United States. Experiments were conducted to characterize a new virus
      identified in symptomatic plants. Molecular analysis revealed a genome
      organization resembling Grapevine leafroll-associated virus 3, the type species
      of the genus Ampelovirus in the family Closteroviridae. The genome of the virus,
      provisionally named blackberry vein banding associated virus (BVBaV), consists of
      18,643 nucleotides and contains 10 open reading frames (ORFs). These ORFs encode
      closterovirid signature replication-associated and quintuple gene block proteins,
      as well as four additional proteins of unknown function. Phylogenetic analyses of
      taxonomically relevant products consistently placed BVBaV in the same cluster
      with GLRaV-3 and other members of the subgroup I of the genus Ampelovirus. The
      virus population structure in the U.S. was studied using the replication
      associated polyprotein 1a, heat shock 70 homolog and minor coat proteins of 25
      isolates. This study revealed significant intra-species variation without any
      clustering among isolates based on their geographic origin. Further analyses
      indicated that these proteins are under stringent purifying selections. High
      genetic variability and incongruent clustering of isolates suggested the possible
      involvement of recombination in the evolution of BVBaV. 

PMID- 24126201
TI  - Temporary cerebral revascularization using a radial artery in the hand-eyeshade
      posture: technical note.
AB  - Kamiyama introduced a unique method of temporary cerebral revascularization using
      a radial artery graft (RAG) in his technical review. We tried original method
      with Sugita frame, and pointed out some disadvantages that include to avoid
      taking instruments or hands in and out, stability of hands, and unrestricted
      usage of brain retractors during temporary bypass between radial artery and M2
      potion of middle cerebral artery (RA-M2 bypass). To solve those disadvantages,
      especially for Sugita head frame users, we here present a modified Kamiyama's
      method of temporary cerebral revascularization with the forearm elevated over the
      face like as hand-eyeshade posture. 

PMID- 24126202
TI  - Would it be ethical to use motivational interviewing to increase family consent
      to deceased solid organ donation?
AB  - We explore the ethics of using motivational interviewing (MI), an evidence-based,
      client-centred and directional counselling method, in conversations with next of
      kin about deceased solid organ donation. After briefly introducing MI and
      providing some context around organ transplantation and next of kin consent, we
      describe how MI might be implemented in this setting, with the hypothesis that MI
      has the potential to bring about a modest yet significant increase in next of kin
      consent rates. We subsequently consider the objection that using MI in this
      context would be manipulative. Although we cannot guarantee that MI would never
      be used in a problematically manipulative fashion, we conclude that its use
      would, nevertheless, be permissible as a potential means to increase next of kin
      consent to deceased solid organ donation. We propose that MI be trialled in
      consent situations with next of kin in nations where there is widespread public
      support for organ donation. 

PMID- 24126203
TI  - Directional specificity and encoding of muscle forces and loads by stick insect
      tibial campaniform sensilla, including receptors with round cuticular caps.
AB  - In many systems, loads are detected as the resistance to muscle contractions. We
      studied responses to loads and muscle forces in stick insect tibial campaniform
      sensilla, including a subgroup of receptors (Group 6B) with unusual round
      cuticular caps in oval-shaped collars. Loads were applied in different directions
      and muscle contractions were emulated by applying forces to the tibial flexor
      muscle tendon (apodeme). All sensilla 1) were maximally sensitive to loads
      applied in the plane of joint movement and 2) encoded muscle forces but did not
      discharge to unresisted movements. Identification of 6B sensilla by stimulation
      of cuticular caps demonstrated that receptor responses were correlated with their
      morphology. Sensilla with small cuticular collars produced small extracellular
      potentials, had low thresholds and strong tonic sensitivities that saturated at
      moderate levels. These receptors could effectively signal sustained loads. The
      largest spikes, derived from sensilla with large cuticular collars, had strong
      dynamic sensitivities and signaled a wide range of muscle forces and loads.
      Tibial sensilla are apparently tuned to produce no responses to inertial forces,
      as occur in the swing phase of walking. This conclusion is supported by tests in
      which animals 'stepped' on a compliant surface and sensory discharges only
      occurred in stance. 

PMID- 24126204
TI  - Electrophysiological evidence of early attentional bias to drug-related pictures
      in chronic cannabis users.
AB  - Behavioral and electrophysiological correlates of attentional bias to cannabis
      related cues were investigated in a marijuana dependent group and a non-user
      group employing a drug Stroop task in which cannabis-related, negative and
      neutral images were presented. Behaviorally, cannabis users were less accurate
      during drug-containing blocks than non-users. Electrophysiologically, in chronic
      marijuana-users, an early positive ERP enhancement over left frontal scalp (EAP,
      200-350ms) was present in response to drug-containing blocks relative to negative
      blocks. This effect was absent in the non-user group. Furthermore, drug
      containing blocks gave rise to enhanced voltage of a posterior P300 (300-400ms),
      and a posterior sustained slow wave (LPP, 400-700ms) relative to negative blocks.
      However, such effects were similar between cannabis users and non-users. Brain
      source imaging in cannabis users revealed a generator for the EAP effect to drug
      stimuli in left ventromedial prefrontal cortex/medial orbitofrontal cortex, a
      region active in fMRI studies of drug cue-reactivity and a target of the core
      dopaminergic mesolimbic pathway involved in the processing of substances of
      abuse. This study identifies the timing and brain localization of an ERP
      correlate of early attentional capture to drug-related pictures in chronic
      marijuana users. The EAP to drug cues may identify a new electrophysiological
      marker with clinical implications for predicting abstinence versus relapse or to
      evaluate treatment interventions. 

PMID- 24126205
TI  - Self-regulation and alcohol use involvement: a latent class analysis.
AB  - Although alcohol use can be problematic, research suggests considerable
      heterogeneity in problems across various drinking classes; particularly among the
      heaviest drinking groups. Differences in self-regulation may differentiate
      drinking classes. The current study evaluated differences in emotional and
      behavioral self-regulation across four empirically derived drinking classes.
      Participants (n=1895 college students) completed online measures of demographics,
      alcohol involvement, and self-regulation. Using latent class analysis (LCA), four
      drinking classes were empirically derived. Moderate drinkers were the largest
      class (38.1%) followed by light drinkers (37.4%), heavy drinkers (17.8%), and
      problem drinkers (6.8%). Each class was predicted by self-regulation indicators
      in the LCA. With the exception of urgency, behavioral self-regulation
      distinguished primarily between light drinkers and the other three classes.
      Emotional self-regulation and urgency were not associated with use, but did
      distinguish among the most problematic class. Specifically, emotional instability
      and urgency were higher in the problem use class than all other classes. Overall,
      the findings suggest important differences in behavioral and emotional self
      regulation across drinking classes that differentially contribute to use and
      consequences. Further, the results highlight the importance of examining
      homogenous subpopulations of drinkers that may differ on indices other than
      consumption. 

PMID- 24126206
TI  - An overview of problematic internet use.
AB  - Problematic Internet use (PIU), which has become a global social issue, can be
      broadly conceptualized as an inability to control one's use of the Internet which
      leads to negative consequences in daily life. The aim of this paper is to give a
      brief overview of the gradually evolving body of literature on PIU. This shows
      that the definitions and diagnostic criteria that have been proposed, and the
      assessment tools that have been developed, stress similarities between PIU,
      addictive behaviours and impulse-control disorders. Disagreements regarding
      diagnostic criteria and the lack of large epidemiological studies have resulted
      in difficulties in establishing the prevalence of PIU in the general population.
      Studies suggest high comorbidity rates between PIU and numerous psychiatric
      disorders highlighting the importance of focusing on comorbidity in treatment.
      There is growing evidence that genetic, personality and individual differences in
      automatic and controlled aspects of self-regulation may promote the development
      of PIU. Pharmacological and psychotherapeutic treatments specific to PIU have
      received limited testing in large, rigorous studies however preliminary evidence
      suggests that both psychotropic medications (Escitalopram, Naltrexone and
      Methylphenidate) and cognitive behaviour therapy may have some utility in the
      treatment of PIU. More research is needed on areas which remain unclear and
      contribute to the prognosis of PIU, in particular the temporal relationships
      between psychiatric disorder and PIU, mechanisms of comorbidity and the more
      subtle psychological changes that occur through Internet use. 

PMID- 24126207
TI  - 5-Year trends in the intention to quit smoking amidst the economic crisis and
      after recently implemented tobacco control measures in Greece.
AB  - OBJECTIVES: The objective of the present study was to explore the trends in the
      intention to quit smoking among adults in Greece between 2006 and 2011, a period
      characterized by financial instability and newly endorsed tobacco control
      initiatives. METHODS: Trend analysis of 3 representative national and cross
      sectional surveys, 'Hellas Health I' (2006), "Hellas Health III" (2010) and
      Hellas Health IV (2011). RESULTS: Since 2006, the intention to quit smoking has
      significantly increased among both genders (33.3% [in 2006] to 42.4% [in 2011],
      p=0.002), among respondents aged >54years (26.9% [in 2006] to 45.1% [in 2011],
      p=0.019) and among residents of rural areas (26.4% [in 2006] to 46.7% [in 2011],
      p=0.001). Both highest (32.1% [in 2006] to 49.4% [in 2011], p=0.036) and lowest
      (31.7% to 46.0%, p=0.021) socioeconomic (SE) strata showed an increase in the
      proportion of smokers who intend to quit. However, in 2011, quit attempts were
      more frequent (35.3%, p=0.009) in smokers of high socioeconomic status. Moreover,
      smoking prevalence has significantly decreased (43.1% [in 2006] to 38.1% [in
      2011], p=0.023), mainly among men (52.4% to 45.7%, p=0.037), respondents of low
      socioeconomic status (38.9% to 29.4%, p=0.008) and residents of urban areas
      (45.2% to 37.9%, p=0.005). CONCLUSIONS: Over the past 5years and possibly as a
      combined result of the implemented tobacco control policies and austerity
      measures, the intention to quit smoking has increased among all SE strata,
      however actual quit attempts were higher among those less disadvantaged. Further
      effort should be made to support quit attempts, especially among vulnerable
      populations.

PMID- 24126208
TI  - Microbial degradation of polyfluoroalkyl chemicals in the environment: a review.
AB  - Polyfluoroalkyl chemicals containing perfluoroalkyl moieties have been widely
      used in numerous industrial and commercial applications. Many polyfluoroalkyl
      chemicals are potential perfluoroalkyl acid (PFAA) precursors. When they are
      released to the environment, abiotic and microbial degradation of non-fluorinated
      functionalities, polyfluoroalkyl and perfluoroalkyl moieties can result in
      perfluoroalkyl carboxylic (PFCAs) and sulfonic acids (PFSAs), such as
      perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). These
      highly persistent and ubiquitously detected PFAAs are the subjects of many
      regulations and actions due to their toxic profiles. In order to confidently
      evaluate the environmental fate and effects of these precursors and their links
      to PFSAs and PFCAs, we present the review into the environmental biodegradability
      studies carried out with microbial culture, activated sludge, soil and sediment
      in the past decade. First, we propose that the knowledge gap caused by the lack
      of direct detection of precursor chemicals in environmental samples can be
      bridged by laboratory investigations of important precursors such as
      fluorotelomer-based compounds and perfluoroalkane sulfonamido derivatives. Then
      we evaluate the experimental setups and methodologies, sampling and sample
      preparation methods, and analytical techniques that have been successfully
      applied. Third, we provide the most updated knowledge on quantitative and
      qualitative relationships between precursors and PFSAs or PFCAs, microbial
      degradation pathways, half-lives of precursors, defluorination potential, and
      novel degradation intermediates and products. In the end, we identify knowledge
      gaps and suggest research directions with regard to future biodegradation
      studies, environmental monitoring and ecotoxicological assessment of
      perfluoroalkyl and polyfluoroalkyl chemicals. 

PMID- 24126209
TI  - Tiny disseminated angiomas from childhood.

PMID- 24126210
TI  - Antiviral and antiproliferative effects of canine interferon-lambda1.
AB  - Interferon (IFN)-lambdas, members of the type III IFN group, were recently
      identified in several vertebrates. Although IFN-lambdas have the potential to be
      utilized as antiviral and antitumor agents in veterinary medicine, the biological
      properties of IFN-lambdas have not yet been studied in companion animals. In this
      study, we analyzed the expression of canine IFN-lambdas and their receptors,
      produced a recombinant canine IFN-lambda1 protein, and investigated its antiviral
      and antiproliferative activities using a canine kidney epithelial cell line, MDCK
      cells. MDCK cells were found to express type III IFN molecules, IFN-lambda1 and
      IFN-lambda3, and the receptors, IFNlambdaR1 and IL10R2. IFN-lambda1 was induced
      faster than IFN-lambda3 by stimulation with poly (I:C). His-tagged IFN-lambda1
      protein expressed in Escherichia coli inhibited cytolytic plaque formation by
      influenza A virus infection, and induced the expression of interferon-stimulated
      genes, Mx1 and OAS1, in MDCK cells. In addition, recombinant IFN-lambda1
      inhibited the proliferation of MDCK cells slightly. These effects were observed
      in a dose-dependent manner. These results indicate that canine IFN-lambda1 has
      antiviral effect, and suggest the potential applicability of canine IFN-lambda1
      as a therapeutic agent.

PMID- 24126212
TI  - [Depression according to age and gender: an analysis in a community].

PMID- 24126211
TI  - Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin
      based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1
      dose-escalation study in healthy adults.
AB  - BACKGROUND: Novel influenza viruses continue to pose a potential pandemic threat
      worldwide. In recent years, plants have been used to produce recombinant
      proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on
      recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1)
      strain of influenza virus, has been manufactured using a plant virus-based
      transient expression technology in Nicotiana benthamiana plants and demonstrated
      to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). METHODS:
      A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single
      blind, dose escalation study was conducted to investigate safety, reactogenicity
      and immunogenicity of an HAC1 formulation at three escalating dose levels (15
      MUg, 45 MUg and 90 MUg) with and without Alhydrogel((r)), in healthy adults 18-50
      years of age (inclusive). Eighty participants were randomized into six study
      vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine
      group. Recipients received two doses of vaccine or placebo (except for the
      monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later
      followed by a dose of placebo). RESULTS: The experimental vaccine was safe and
      well tolerated, and comparable to placebo and the approved monovalent H1N1
      vaccine. Pain and tenderness at the injection site were the only local solicited
      reactions reported following vaccinations. Nearly all adverse events were mild to
      moderate in severity. The HAC1 vaccine was also immunogenic, with the highest
      seroconversion rates, based on serum hemagglutination-inhibition and virus
      microneutralization antibody titers, in the 90 MUg non-adjuvanted HAC1 vaccine
      group after the second vaccine dose (78% and 100%, respectively). CONCLUSIONS:
      This is the first study demonstrating the safety and immunogenicity of a plant
      produced subunit H1N1 influenza vaccine in healthy adults. The results support
      further clinical investigation of the HAC1 vaccine as well as demonstrate the
      feasibility of the plant-based technology for vaccine antigen production.

PMID- 24126213
TI  - Structure-function analysis of the DNA translocating portal of the bacteriophage
      T4 packaging machine.
AB  - Tailed bacteriophages and herpesviruses consist of a structurally well conserved
      dodecameric portal at a special 5-fold vertex of the capsid. The portal plays
      critical roles in head assembly, genome packaging, neck/tail attachment, and
      genome ejection. Although the structures of portals from phages phi29, SPP1, and
      P22 have been determined, their mechanistic roles have not been well understood.
      Structural analysis of phage T4 portal (gp20) has been hampered because of its
      unusual interaction with the Escherichia coli inner membrane. Here, we predict
      atomic models for the T4 portal monomer and dodecamer, and we fit the dodecamer
      into the cryo-electron microscopy density of the phage portal vertex. The core
      structure, like that from other phages, is cone shaped with the wider end
      containing the "wing" and "crown" domains inside the phage head. A long "stem"
      encloses a central channel, and a narrow "stalk" protrudes outside the capsid. A
      biochemical approach was developed to analyze portal function by incorporating
      plasmid-expressed portal protein into phage heads and determining the effect of
      mutations on head assembly, DNA translocation, and virion production. We found
      that the protruding loops of the stalk domain are involved in assembling the DNA
      packaging motor. A loop that connects the stalk to the channel might be required
      for communication between the motor and the portal. The "tunnel" loops that
      project into the channel are essential for sealing the packaged head. These
      studies established that the portal is required throughout the DNA packaging
      process, with different domains participating at different stages of genome
      packaging. 

PMID- 24126214
TI  - Body mass index, weight change, and clinical progression in mild cognitive
      impairment and Alzheimer disease.
AB  - The speed and severity of clinical progression after Alzheimer disease (AD)
      diagnosis varies and depends on multiple factors, most not well elucidated. We
      assessed whether body mass index (BMI) and 1-year weight change (WC) are
      associated with clinical progression in amnestic mild cognitive impairment (aMCI)
      and early-stage AD. Longitudinal data comprising 2268 aMCI and 1506 AD
      participants in the National Alzheimer's Coordinating Center's Uniform Data Set
      were used to examine nuances of clinical progression by BMI and WC, as well as
      potential variations in associations by age, sex, BMI (WC model), or
      apolipoprotein E genotype. In aMCI, high BMI (vs. moderate BMI) was associated
      with slower progression; weight loss (vs. no WC) was associated with faster
      progression. In AD, no significant differences were observed in clinical
      progression by BMI or WC. The association between BMI and clinical progression
      varied significantly by apolipoprotein E genotype in AD, and the association
      between WC and clinical progression varied significantly by sex and BMI in aMCI.
      Baseline BMI and 1-year WC in late life may serve as early prognostic indicators
      in aMCI and early-stage AD. If replicated, these results may help in counseling
      patients on anticipated clinical progression and suggest windows of opportunity
      for intervention. 

PMID- 24126215
TI  - The mild cognitive impairment stage of dementia with Lewy bodies and Parkinson
      disease: a comparison of cognitive profiles.
AB  - BACKGROUND: Recent studies have demonstrated that structural and pathologic
      changes are more severe in patients with dementia with Lewy bodies (DLB) than in
      those with Parkinson disease with dementia (PDD). We investigated
      neuropsychological characteristics of patients with mild cognitive impairment
      (MCI) stage of DLB (DLB-MCI) and PD (PD-MCI) based on the hypothesis that the
      pathologic differences between DLB and PDD can influence cognitive profiles in
      the MCI stage of these diseases. METHODS: Baseline demographic characteristics
      and neuropsychological data obtained from patients with DLB-MCI (n=20) and PD-MCI
      (n=46) were compared. RESULTS: The patients with DLB-MCI showed poorer cognitive
      performance in the Stroop, Go-No-Go, and semantic fluency tests compared with
      those with PD-MCI. In addition, patients with DLB-MCI had lower scores on visual
      and verbal memory performance and in the visuospatial domain compared with PD-MCI
      patients. CONCLUSIONS: Our results demonstrate that patients with DLB-MCI have
      more severe cognitive impairment in frontal executive, memory, and visuospatial
      functions than those with PD-MCI. These data suggest that differences in
      pathologic substrates between PDD and DLB may begin in the MCI stage of the 2
      diseases and may lead to differences in cognitive profiles.

PMID- 24126216
TI  - Vascular risk factors and cognitive decline in a population sample.
AB  - We examined several vascular factors in relation to the rates of decline in 5
      cognitive domains in a population-based cohort. In an age-stratified random
      sample (N=1982) aged 65+ years, we assessed at baseline the cognitive domains of
      attention, executive function, memory, language, and visuospatial function, and
      also vascular, inflammatory, and metabolic indices. Random effects models
      generated slopes of cognitive decline over the next 4 years; linear models
      identified vascular factors associated with these slopes, adjusting for
      demographics, baseline cognition, and potential interactions. Several vascular
      risk factors (history of stroke, diabetes, central obesity, C-reactive protein),
      although associated with lower baseline cognitive performance, did not predict
      rate of subsequent decline. APOE*4 genotype was associated with accelerated
      decline in language, memory, and executive functions. Homocysteine elevation was
      associated with faster decline in executive function. Hypertension (history or
      systolic blood pressure >140 mm Hg) was associated with slower decline in memory.
      Baseline alcohol consumption was associated with slower decline in attention,
      language, and memory. Different indices of vascular risk are associated with low
      performance and with rates of decline in different cognitive domains.
      Cardiovascular mechanisms explain at least some of the variance in cognitive
      decline. Selective survival may also play a role. 

PMID- 24126217
TI  - Rituximab-based chemoimmunotherapy prolongs survival of patients with chronic
      lymphocytic leukemia independently of the time of administration.
AB  - BACKGROUND: The combination of purine analogues (PA) and rituximab
      (chemoimmunotherapy) is considered the treatment of choice for CLL. The aim of
      this study was to determine whether chemoimmunotherapy prolonged the overall
      survival in patients with CLL from a single center. PATIENTS AND METHODS: From
      1980 to 2010, 273 patients with CLL received: (1) PA (n = 159); and (2) PA plus
      rituximab (PA+R) (n = 114). All treated patients were included in the analysis,
      regardless of time at which treatment was administered, duration of therapy, and
      response. RESULTS: Patients from the PA and PA+R groups were well balanced for
      demographic, clinical, and biologic features. At 8 years, the survival from
      diagnosis of the PA+R group was 88% (95% confidence interval [CI], 82-94%)
      compared with 68% (95% CI, 60-76%) for the PA group (P < .001). When survival of
      patients treated with PA+R was analyzed according to the time of treatment
      administration (first- [n = 55] vs. second or more lines [n = 59]), no
      significant differences were observed (8-year overall survival 89% vs. 87%,
      respectively; P = .8). CONCLUSION: Chemoimmunotherapy prolonged the survival of
      patients with CLL and this effect was independent of the phase of the disease at
      which treatment was given.

PMID- 24126218
TI  - Mephedrone interactions with cocaine: prior exposure to the 'bath salt'
      constituent enhances cocaine-induced locomotor activation in rats.
AB  - Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs
      of abuse is now commonplace, but knowledge about interactions between these drugs
      is sparse. The present study was designed to test the hypothesis that prior MEPH
      exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine
      (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg),
      or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug
      absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or
      MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine
      challenge produced greater locomotor activity after pretreatment with cocaine or
      MEPH than after pretreatment with saline. METH challenge produced greater
      locomotor activity after METH pretreatment than after saline pretreatment;
      however, locomotor activity in rats pretreated with MEPH or saline and then
      challenged with METH was not significantly different. The locomotor response to
      MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15
      mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced
      locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross
      sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross
      sensitization was not bidirectional and did not extend to METH, suggesting that
      the phenomenon is sensitive to specific psychostimulants. 

PMID- 24126219
TI  - Redefining stage I endometrial cancer: incorporating histology, a binary grading
      system, myometrial invasion, and lymph node assessment.
AB  - OBJECTIVE: We propose a new staging system for stage I endometrial cancer and
      compare its performance to the 1988 and 2009 International Federation of
      Gynecology and Obstetrics (FIGO) systems. METHODS: We analyzed patients with 1988
      FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade
      carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade
      carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas
      (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA.
      Low-grade carcinoma with less than half myometrial invasionIB. High-grade
      carcinoma with no myometrial invasionIC. Low-grade carcinoma with half or greater
      myometrial invasionID. High-grade carcinoma with any myometrial invasion RESULTS:
      Data from 1843 patients were analyzed. When patients were restaged with our
      proposed system, the 5-year overall survival significantly differed (P < 0.001):
      IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1,
      81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate
      for the proposed system was 0.627 (95% confidence interval, 0.590-0.664) and was
      superior to the concordance probability estimate of 0.530 (95% confidence
      interval, 0.516-0.544) for the 2009 FIGO system. CONCLUSIONS: By incorporating
      histological subtype, grade, myometrial invasion, and whether lymph nodes were
      removed, our proposed system for stage I endometrial cancer has a superior
      predictive ability over the 2009 FIGO staging system and provides a novel binary
      grading system (low-grade including endometrioid grade 1-2 lesions; high-grade
      carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid
      carcinomas).

PMID- 24126221
TI  - Current controversies in radiotherapy for nasopharyngeal carcinoma (NPC).
AB  - Radiotherapy has a good track record in the treatment of NPC, yet the late
      toxicity profile and local failure rate for locally advanced disease remain a
      concern. Modern RT techniques incorporating IMRT and IGRT have widened our
      potential in treating NPC more effectively, and shall be regarded as the standard
      of care. Out of the various dose fractionation regimens in IMRT, 70 Gy in 35
      fractions or the mini-SIB proves to be safe in combination with chemotherapy, but
      any further attempt of dose escalation must be tried out with extreme caution to
      avoid severe toxicities. CT-MRI image fusion improves the accuracy of GTV
      delineation, whereas the role of PET-CT has yet to be verified. RTOG definition
      of the CTV provides a reasonable template for the inclusion of sites at risk of
      microscopic involvement, and fine tuning has to be made in the future based on
      careful analysis of the pattern of local failure with long term follow-up.
      Toxicity reduction via radiation volume or dose reduction is tempting, but once
      again it has to be tested under scrutiny. Retrospective data have emerged that
      suggest a benefit of using adaptive IMRT replanning in NPC, however the optimal
      timing or frequency of replanning is still unclear. Future prospective studies
      are thus required to evaluate the cost-effectiveness of adaptive RT and
      streamline the workflow logistics before it can be widely accepted in routine
      practice.

PMID- 24126220
TI  - Sustained delivery of a HIF-1 antagonist for ocular neovascularization.
AB  - Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 (HIF
      1) transcriptional activity by blocking its binding to DNA. Intraocular
      injections of DXR or DNR suppressed choroidal and retinal neovascularization
      (NV), but also perturbed retinal function as demonstrated by electroretinograms
      (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol
      and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when
      placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular
      injection of DXR-PSA-PEG3 nanoparticles (1 or 10 MUg DXR content) reduced HIF-1
      responsive gene products, strongly suppressed choroidal and retinal NV, and did
      not cause retinal toxicity. In transgenic mice that express VEGF in
      photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 MUg DXR
      content) suppressed NV for at least 35 days. Intraocular injection of DXR-PSA
      PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained DXR
      conjugate release with detectable levels in aqueous humor and vitreous for at
      least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate
      formulated into controlled-release particles that maximizes efficacy and duration
      of activity, minimizes toxicity, and provides a promising new chemical entity for
      treatment of ocular NV.

PMID- 24126222
TI  - Oxidative and antioxidative mechanisms in oral cancer and precancer: a review.
AB  - Development of cancer in humans is a multistep process. Complex series of
      cellular and molecular changes participating in cancer development are mediated
      by a diversity of endogenous and exogenous stimuli and important amongst this is
      generation of reactive oxygen species (ROS). Reactive radicals and non-radicals
      are collectively known as ROS. These can produce oxidative damage to the tissues
      and hence are known as oxidants in biological system. Many researchers have
      documented the role of ROS in both initiation and promotion of multistep
      carcinogenesis. To mitigate the harmful effects of free radicals, all aerobic
      cells are endowed with extensive antioxidant defence mechanisms. Lowered
      antioxidant capacity or the oxidant-antioxidant imbalance can lead to oxidative
      damage to cellular macromolecules leading to cancer. Oral cavity cancer is an
      important cancer globally and tobacco is the primary etiological factor in its
      development. Tobacco consumption exposes the oral epithelium to toxic oxygen and
      nitrogen free radicals that can affect host antioxidant defence mechanisms.
      Elevated levels of ROS and Reactive Nitrogen Species (RNS) and lowered
      antioxidants are found in oral precancer and cancer. Protection can be provided
      by various antioxidants against deleterious action of these free radicals.
      Treatment with antioxidants has the potential to prevent, inhibit and reverse the
      multiple steps involved in oral carcinogenesis. This review is an attempt to
      understand the interesting correlation between ROS and RNS mediated cell damage
      and enzymatic and non-enzymatic defence mechanisms involved in oral cancer
      development and its progression and the use of antioxidants in oral cancer
      prevention and treatment. 

PMID- 24126224
TI  - Tailored immunotherapy for HPV positive head and neck squamous cell cancer.
AB  - Human papilloma virus (HPV) associated oropharynx carcinoma (OPC) is increasingly
      common, with a distinct biology from HPV negative OPC. In spite of this better
      prognosis, morbidity is significant and treatment related after effects can be
      debilitating. Because the foreign viral proteins that drive HPV+ cancers are
      known, there are multiple options for tailored immune therapies. Herein we review
      the immunologic basis for disease and emerging immune therapies. The oncogenesis
      of HPV+ SCCHN goes beyond cell cycle deregulation, and relies on the immune
      escape through (E5, E6, and E7) downregulating antigen processing, interferon
      response, as well as STAT-1 signaling. Individual susceptibilities to HPV
      infection may vary. The treatment of HPV+ cancers has had a wide range of
      successes and failures. Perhaps the shining example of immunoprevention has been
      the L1 protein vaccines developed for cervical cancer prevention, however this
      vaccine has not been beneficial for people already infected. Therefore multiple
      strategies have been employed in the cancer therapeutic realm for people with
      existing disease. These agents range from peptides, to viral vectors, to adoptive
      cell therapy. In this review we consider the work done in both SCCHN and cervical
      cancer, as these therapeutic targets are the similar. The listed studies are not
      exhaustive, but rather illustrate experimental design and approach. 

PMID- 24126225
TI  - Reduced epidermal thickness, nerve degeneration and increased pain-related
      behavior in rats with diabetes type 1 and 2.
AB  - To examine the mechanisms contributing to pain genesis in diabetic neuropathy, we
      investigated epidermal thickness and number of intraepidermal nerve fibers in rat
      foot pad of the animal model of diabetes type 1 and type 2 in relation to pain
      related behavior. Male Sprague-Dawley rats were used. Diabetes type 1 was induced
      with intraperitoneal injection of streptozotocin (STZ) and diabetes type 2 was
      induced with a combination of STZ and high-fat diet. Control group for diabetes
      type 1 was fed with regular laboratory chow, while control group for diabetes
      type 2 received high-fat diet. Body weights and blood glucose levels were
      monitored to confirm induction of diabetes. Pain-related behavior was analyzed
      using thermal (hot, cold) and mechanical stimuli (von Frey fibers, number of
      hyperalgesic responses). Two months after induction of diabetes, glabrous skin
      samples from plantar surface of the both hind paws were collected. Epidermal
      thickness was evaluated with hematoxylin and eosin staining. Intraepidermal nerve
      fibers quantification was performed after staining skin with polyclonal antiserum
      against protein gene product 9.5. We found that induction of diabetes type 1 and
      type 2 causes significant epidermal thinning and loss of intraepidermal nerve
      fibers in a rat model, and both changes were more pronounced in diabetes type 1
      model. Significant increase of pain-related behavior two months after induction
      of diabetes was observed only in a model of diabetes type 1. In conclusion,
      animal models of diabetes type 1 and diabetes type 2 could be used in
      pharmacological studies, where cutaneous changes could be used as outcome
      measures for predegenerative markers of neuropathies. 

PMID- 24126223
TI  - Promising systemic immunotherapies in head and neck squamous cell carcinoma.
AB  - Patients with head and neck squamous cell carcinoma (HNSCC) demonstrate poor
      survival and significant treatment morbidity with standard therapy. The immune
      profile in HNSCC, whether caused by carcinogen exposure or human papillomavirus
      (HPV), is notably immunosuppressive. Early clinical trials of immunotherapy in
      HNSCC were troubled by systemic toxicity or difficulties in local administration.
      Now, interest in immunotherapy has been revitalized by mechanistic insights into
      immune evasion by HNSCC, coupled to ongoing development of novel immunotherapies.
      This review will summarize immune escape mechanisms in HNSCC, namely
      downregulation of tumor antigen (TA) presentation, aberrant regulation of the
      signal transducer and activator of transcription (STAT) family, the
      immunosuppressive cytokine milieu, and dysregulation of immune effector cells.
      Therapeutic strategies hypothesized to specifically counter HNSCC
      immunosuppression will then be discussed. We will survey TA- targeted monoclonal
      antibodies (mAb), including the prototype cetuximab, as well as adjunctive
      strategies to enhance antibody-dependent cell-mediated cytotoxicity. We will
      review immunomodulation to restore STAT1/STAT3 activation balance. Examples of
      mAb therapy to block immunosuppressive cytokines, such as interleukin-6 or VEGF,
      will be provided. mAbs which release co-inhibitory T cell receptors such as CTLA
      4 and PD-1, overexpressed in HNSCC, also hold therapeutic promise. Finally, we
      will describe principles for therapeutic vaccination in HPV-associated HNSCC,
      where non-host TAs such as viral oncoproteins represent ideal targets, and HPV
      negative HNSCC, where p53 is a promising target. Insights into immunosuppression
      in HNSCC have elucidated mechanistic targets for immunotherapy. Rational clinical
      investigation may lead to effective stand alone or combinatorial treatment
      approaches. 

PMID- 24126226
TI  - Differential pattern of neuroprotection in lumbar, cervical and thoracic spinal
      cord segments in an organotypic rat model of glutamate-induced excitotoxicity.
AB  - Glutamate-induced excitotoxicity is a major contributor to motor neuron (MN)
      degeneration in disorders such as amyotrophic lateral sclerosis (ALS), stroke and
      spinal cord injury. Numerous in vitro and in vivo models have been developed to
      evaluate the efficacy and mode of action of neuroprotective agents. However, the
      dominance of glutamate receptor-subtype in the different regions of the spinal
      cord in these models has generally been overlooked. This study first compared the
      neuroprotective effect of administering glutamate receptor antagonists, (+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) and 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), into a serum-free excitotoxic organotypic in
      vitro system, on the survival of MNs located in the lumbar area of spinal cord.
      The poor neuroprotection provided by MK-801 (NMDA (N-methyl-D-aspartate)
      antagonist) in comparison to CNQX (AMPA/KA (a-amino-3-hydroxy-5-methyl-4
      isoxazole propionate/kainate) antagonist), raised the hypothesis that the extent
      of engagement by glutamate receptor sub-types in the mechanism of excitotoxicity
      may differ within different populations of MNs. The consequent examination of MN
      susceptibility to glutamate-induced excitotoxicity in relation to the rostro
      caudal level from which MN originated revealed a differential glutamate receptor
      sub-type dominance at different spinal cord regions (i.e. cervical, thoracic and
      lumbar). In the cervical and lumbar regions, the AMPA receptor was the main
      contributor to MN excitotoxicity, whereas in thoracic regions, the NMDA receptor
      was the main contributor. This study provides a new way of looking at mechanisms
      leading to glutamate-induced excitotoxicity in MN and may therefore be important
      for the development of treatment strategies in protection of spinal MNs in
      neurodegenerative disease and traumatic injury.

PMID- 24126227
TI  - The placement of DPP-4 inhibitors in clinical practice recommendations for the
      treatment of type 2 diabetes.
AB  - OBJECTIVE: To review the most recent clinical data on the safety and efficacy of
      dipeptidyl peptidase-4 (DPP-4) inhibitors and to evaluate their position in
      current treatment guidelines and algorithms. METHODS: PubMed searches were
      performed to identify published data regarding both the safety and efficacy of
      DPP-4 inhibitors approved for use in the United States and clinical guidelines
      describing recommendations for their use. RESULTS: In the past 2 years, more than
      100 publications have added clinical trial data on DPP-4 inhibitors to the
      medical literature. Since becoming available in 2006, these agents have
      demonstrated an excellent safety/tolerability profile, and as add-on to
      metformin, DPP-4 inhibitors may have comparable glycemic efficacy as other oral
      agents. As a result, DPP-4 inhibitors have assumed roles in clinical practice
      guidelines and treatment algorithms that are comparable to the sulfonylurea
      class. Advantages of DPP-4 inhibitors include an oral route of administration, a
      mechanism of action based on glucose-stimulated insulin secretion, and a low risk
      of hypoglycemia. The main disadvantage associated with this class is a relatively
      high cost. There is also less clinical experience with DPP-4 agents than classes
      of agents that have been in use for decades; however, long-term data on the
      safety and efficacy of DPP-4 agents will be available in the near future to
      refine their place in therapy. From 2 large clinical trials recently reported,
      EXAMINE and SAVOR, this class of agents does not increase overall adverse
      cardiovascular outcomes nor the risk of pancreatitis or pancreatic cancer.
      CONCLUSION: Based on comparisons of nonglycemic effects such as risk of
      hypoglycemia, weight gain, and durability, DPP-4 inhibitors may be considered as
      an alternative to sulfonylureas. However, direct cost may be a determining factor
      in the choice of therapy.

PMID- 24126228
TI  - Luteoma of pregnancy associated with nearly complete virilization of genetically
      female twins.
AB  - OBJECTIVE: To describe a pregnancy that was complicated by the virilization of
      the mother and two 46XX infants. METHODS: We outline the clinical presentation
      and diagnosis of the virilization of a mother and her twins, reviewing pertinent
      literature. RESULTS: We report the case of a 40-year-old Caucasian female who
      conceived a trichorionic triplet pregnancy through in vitro fertilization (IVF)
      but underwent cytoreduction at 13 weeks of gestation, leaving a diamniotic
      dichorionic twin pregnancy. At 16 weeks of gestation the mother experienced
      increasing acne, facial hair, and deepening of her voice. Due to preeclampsia,
      the twins were delivered via caesarean section at 33 weeks of gestation. The
      infants had male-appearing external genitalia (Prader score IV-V) but no palpable
      gonads. Congenital adrenal hyperplasia was ruled out for both twins and they were
      both found to have a uterus and a 46XX karyotype. Maternal testosterone level was
      elevated at birth (1,981 ng/dL), but the infants had normal levels. Maternal
      testosterone levels returned to normal after delivery, consistent with a luteoma
      of pregnancy, although imaging was negative for a mass. CONCLUSION: This is the
      second reported case of complete virilization associated with a luteoma of
      pregnancy. Whether or not IVF and related procedures increase the risk for a
      luteoma and whether or not fetal reduction procedures disrupt placental
      aromatases and increase the risk of virilization in the face of elevated androgen
      levels are questions that require further research.

PMID- 24126229
TI  - Pasireotide and mifepristone: new options in the medical management of Cushing's
      disease.
AB  - OBJECTIVE: To review and evaluate medical therapies for Cushing's disease (CD),
      with an emphasis on recent clinical trial experience with pasireotide and
      mifepristone, and to discuss the therapeutic potential and appropriate selection
      of these compounds in this patient population. METHODS: Recently published Phase
      III trial data for each compound are reviewed and assessed, and relative benefits
      and risks are examined and compared where possible. RESULTS: Mifepristone and
      pasireotide are both potentially beneficial for CD patients but have greatly
      dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts
      at the level of the pituitary adenoma, reducing cortisol levels through
      inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide
      reduces insulin secretion and incretin hormone response and is associated with
      significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the
      signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2)
      blockade, but this approach raises serum cortisol levels and increases risk for
      adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While
      response to pasireotide can be monitored via measurements of serum, urine, or
      late-night salivary cortisol, evaluation of response to mifepristone is solely
      based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body
      weight/composition). CONCLUSION: Management of persistent CD is challenging, and
      the decision to initiate medical treatment hinges on many factors. Pasireotide
      may be a more attractive option for most patients due to its action at the
      underlying tumor and the ability to monitor biochemical responses. However,
      mifepristone may be more appropriate when it is necessary to avoid or minimize
      risk for hyperglycemia-related complications.

PMID- 24126230
TI  - Complete blood counts are frequently abnormal 1 year after dosimetry-guided
      radioactive iodine therapy for metastatic thyroid cancer.
AB  - OBJECTIVE: Radioactive iodine (RAI) has been associated with hematologic
      abnormalities. Previous research has shown that even a single dose of RAI can
      cause changes in the peripheral complete blood count (CBC). It is unclear if the
      use of dosimetry guidance would prevent the effects of high doses of RAI on bone
      marrow suppression. METHODS: CBC at baseline was compared to a CBC obtained 1
      year after the last RAI treatment in 50 thyroid cancer patients that received
      >=250 mCi RAI during the course of their disease. Cumulative dose, number of
      treatments, patients' age, and the use of external beam radiation therapy (EBRT)
      were considered in the analysis. RESULTS: We observed a small but statistically
      significant decrease in hemoglobin (Hb), hematocrit (Hct), and platelet (Plt)
      counts at 1 year in 50 patients who had received >=250 mCi RAI. We did not find a
      significant change in white blood cell count (WBC). Approximately 60% of patients
      who developed anemia had concomitant WBC and Plt abnormalities. RAI dose, number
      of treatments, and age at diagnosis did not confer a higher risk of bone marrow
      suppression. CONCLUSION: High cumulative activities of RAI administered under
      dosimetric guidance are associated with a small but statistically significant
      decreases in Hb, Hct, and Plt counts. The clinical implications of these changes,
      if any, are unclear. The benefits obtained with high doses of RAI, when
      indicated, are likely to outweigh the minimal hematologic risks observed in the
      present study.

PMID- 24126231
TI  - Recurrent pituitary macroadenoma with increased plasma ACTH precursors that cross
      react in a commonly used ACTH immunoassay.

PMID- 24126232
TI  - Evolving approaches in managing radioactive iodine-refractory differentiated
      thyroid cancer.
AB  - OBJECTIVE: To discuss the approach to care of patients with advanced
      differentiated thyroid cancer (DTC), in particular those with radioactive iodine
      (RAI)-refractory disease, and the transition to systemic treatment. METHODS: A
      PubMed search was conducted using the search terms "radioactive iodine
      refractory, differentiated thyroid cancer and treatment" restricted to a 2000
      2012 timeframe, English language, and humans. Relevant articles were identified
      from the bibliographies of selected references. Four patient cases are presented
      to illustrate the clinical course of RAI-refractory DTC. RESULTS: The current
      standard of care for early stage DTC could include surgery, RAI in some cases,
      and thyroid hormone suppression. For advanced RAI-refractory DTC, clinical
      practice guidelines established by the National Comprehensive Cancer Network and
      the American Thyroid Association recommend, as one option, the use of systemic
      therapy, including kinase inhibitors. Numerous trials are underway to evaluate
      the clinical benefit of these targeted therapies. CONCLUSION: Preliminary results
      are encouraging with respect to the clinical benefit of targeted systemic
      therapies. However, at present there is no consensus on the criteria that define
      RAI-refractory disease and the optimal timing for transition to systemic therapy.
      There remains a need to establish common criteria to enhance patient care and
      enable better comparison across clinical studies.

PMID- 24126233
TI  - Visual vignette.

PMID- 24126234
TI  - Genetic link between heme oxygenase and the signaling pathway of DNA damage in
      Drosophila melanogaster.
AB  - Heme oxygenase (HO) is a rate-limiting step of heme degradation, which catalyzes
      the conversion of heme into biliverdin, iron, and CO. HO has been characterized
      in microorganisms, insects, plants, and mammals. The mammalian enzyme
      participates in adaptive and protective responses to oxidative stress and various
      inflammatory stimuli. The present study reports that eye imaginal disc-specific
      knockdown of the Drosophila HO homologue (dHO) conferred serious abnormal eye
      morphology in adults, resulting in the generation of reactive oxygen species and
      apoptosis in third-instar larvae. Oxidative stress frequently induces DNA lesions
      that are recognized by damage sensors, including ataxia-telangiectasia mutated
      (ATM) and ataxia-telangiectasia and rad3-related (ATR) proteins. The knockdown of
      dHO took place in G0/G1-arrested cells posterior to the morphogenetic furrow and
      thus prevented these cells from entering S-phase, with an increase in the level
      of histone H2A.V, a DNA damage marker. Moreover, the knockdown of dHO resulted in
      the enhancement of the rough eye phenotype in ATM-deficient flies or was lethal
      in ATR-deficient flies. These results indicate that dHO functions in control of
      the signal pathway of DNA damage. On the other hand, genetic crosses with a
      collection of Drosophila deficiency stocks allowed us to identify eight genomic
      regions, each deletion of which caused suppression of the rough eye phenotype
      induced by dHO knockdown. This information should facilitate the identification
      of HO regulators in Drosophila and clarification of the roles of HO in eye
      development. 

PMID- 24126235
TI  - Developmental regulation of neuroligin genes in Japanese ricefish (Oryzias
      latipes) embryogenesis maintains the rhythm during ethanol-induced fetal alcohol
      spectrum disorder.
AB  - Although prenatal alcohol exposure is the potential cause of fetal alcohol
      spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet
      unknown. We have used Japanese ricefish (Oryzias latipes) embryogenesis as an
      animal model of FASD and reported that this model has effectively generated
      several phenotypic features in the cardiovasculature and neurocranial cartilages
      by developmental ethanol exposure which is analogous to human FASD phenotypes. As
      FASD is a neurobehavioral disorder, we are searching for a molecular target of
      ethanol that alters neurological functions. In this communication, we have
      focused on neuroligin genes (nlgn) which are known to be active at the
      postsynaptic side of both excitatory and inhibitory synapses of the central
      nervous system. There are six human NLGN homologs of Japanese ricefish reported
      in public data bases. We have partially cloned these genes and analyzed their
      expression pattern during normal development and also after exposing the embryos
      to ethanol. Our data indicate that the expression of all six nlgn genes in
      Japanese ricefish embryos is developmentally regulated. Although ethanol is able
      to induce developmental abnormalities in Japanese ricefish embryogenesis
      comparable to the FASD phenotypes, quantitative real-time PCR (qPCR) analysis of
      nlgn mRNAs indicate unresponsiveness of these genes to ethanol. We conclude that
      the disruption of the developmental rhythm of Japanese ricefish embryogenesis by
      ethanol that leads to FASD may not affect the nlgn gene expression at the message
      level. 

PMID- 24126236
TI  - Hepatocellular adenomatosis: what should the term stand for!
AB  - In 1985, adenomatosis, a term coined to mean ten or more nodules, was considered
      as a specific entity different from hepatocellular adenoma (HCA) whether single
      or multiple. In the 2000s the term has lost its individuality. The great
      contribution of the classification was to clearly demonstrate that in all
      hepatocellular subtypes and in particular etiologies such as glycogenosis and
      male hormone administration, HCA could be solitary, multiple (<10) or multiple
      (>10: adenomatosis). Management of hepatocellular adenomatosis may not be
      different from solitary or multiple HCA. To keep its specificity in terms of
      management and prognosis compared to solitary or multiple HCA, it is necessary to
      indicate the number of nodules including the combination of three parameters:
      size, location and subtypes. When the classical armentarium to treat nodules is
      not possible or too risky, embolization or liver transplantation remains the only
      therapeutic options. 

PMID- 24126237
TI  - Failure to suppress markers of bone turnover on first-line hormone therapy for
      metastatic prostate cancer is associated with shorter time to skeletal-related
      event.
AB  - BACKGROUND: Elevated markers of bone turnover are prognostic for shorter survival
      in castration-resistant prostate cancer. We aimed to determine the prognostic
      value of bone turnover markers in metastatic hormone-sensitive prostate cancer.
      PATIENTS AND METHODS: Markers of bone turnover (urine deoxypyridinoline [DPD] and
      N-telopeptide, serum bone alkaline phosphatase (AP), and osteocalcin [OC]) from
      baseline and after 6 months of study were assessed in men enrolled in a
      prospective metastatic prostate cancer trial with androgen deprivation therapy
      (ADT) with or without risedronate (ClinicalTrials.gov, NCT00216060). RESULTS:
      Serum samples were collected from 63 patients with bone involvement and a median
      follow-up of 39.7 months. A multivariate model using Cox regression-which
      included prostate-specific antigen (PSA) nadir, bisphosphonate treatment, and
      extent of metastases-showed that suppression of bone turnover markers after 6
      months of therapy compared with baseline was significantly associated with longer
      skeletal-related event (SRE)-free survival. ADT without bisphosphonate therapy
      was also associated with a decline in markers of bone turnover, presumably
      resulting from direct anticancer activity. Elevated baseline bone turnover
      markers were not prognostic. CONCLUSION: Failure to suppress bone turnover while
      receiving ADT, even when otherwise responding to therapy, may identify patients
      with hormone-sensitive metastatic prostate cancer who are destined for a shorter
      time to SREs and progression.

PMID- 24126238
TI  - The validity and utility of the MD Anderson Symptom Inventory in patients with
      prostate cancer: evidence from the Symptom Outcomes and Practice Patterns (SOAPP)
      data from the Eastern Cooperative Oncology Group.
AB  - BACKGROUND: The MD Anderson Symptom Inventory (MDASI) is a psychometrically
      validated patient-reported outcome measure that assesses the severity and impact
      of multiple symptoms related to cancer and its treatment and has the potential to
      guide treatment specific to patients with prostate cancer. Although the original
      MDASI validation study encompassed various cancer types, the instrument's
      psychometric properties have not been examined in a large homogeneous sample of
      patients with prostate cancer. PATIENTS AND METHODS: This study involved
      secondary analysis of data from the nationwide multicenter Eastern Cooperative
      Oncology Group (ECOG) SOAPP (Symptom Outcomes and Practice Patterns) study, which
      enrolled patients from 38 ECOG-affiliated institutions, including 6 academic
      centers and 32 community clinics. Data were used to establish the psychometric
      properties of the MDASI in a subsample of 320 patients with prostate cancer. The
      instrument was administered twice, approximately 1 month apart. RESULTS: The
      MDASI demonstrated good internal consistency and test-retest reliability (with
      Cronbach alphas of >= .84 and intraclass correlations of >= 0.76 for all
      subscales), strong ability to discriminate between clinically different patient
      groups (by performance status, tumor response, and disease stage), and high
      sensitivity in detecting symptom change (with respect to patient-reported quality
      of life [QOL] between the baseline and 1-month follow-up visits). CONCLUSION: The
      MDASI is a valid, reliable, and sensitive symptom-assessment instrument that can
      be used with confidence in descriptive and clinical studies of symptom status in
      patients with prostate cancer.

PMID- 24126239
TI  - Computed tomography characteristics of unresectable primary renal cell carcinoma
      treated with neoadjuvant sunitinib.
AB  - Neoadjuvant sunitinib might downsize unresectable renal cell carcinoma (RCC) and
      enable nephrectomy in a subset of patients. After neoadjuvant sunitinib in 27 RCC
      patients, tumors were resected in 13 patients. Higher attenuation using computed
      tomography (CT) scans and favorable response according to Morphology,
      Attenuation, Size, and Structure (MASS) criteria after 2 cycles of sunitinib were
      independent predictors of subsequent tumor resection. INTRODUCTION: In patients
      with locally advanced and metastatic RCC, selection criteria for nephrectomy are
      imprecise. Neoadjuvant sunitinib might downsize unresectable tumors and enable
      nephrectomy. CT scans of unresectable primary RCCs before and after neoadjuvant
      sunitinib were retrospectively reviewed to identify radiographic features
      associated with patient selection for surgery. PATIENTS AND METHODS: CT scans of
      27 patients with RCC (31 tumors) treated with neoadjuvant sunitinib were
      performed as part of a prospective clinical trial. After neoadjuvant sunitinib,
      tumors were surgically resected in 13 patients (17 tumors) and not resected in 14
      patients (14 tumors). Response to treatment with sunitinib was assessed with
      Response Evaluation Criteria in Solid Tumors and MASS criteria. RESULTS: On the
      contrast-enhanced CT scan before nephrectomy compared with the baseline CT scan,
      88% of resected tumors demonstrated decreased size (median decrease 26%; -2.0 cm;
      P < .001), 88% had decreased attenuation (median decrease 30%; -27 Hounsfield
      units; P = .004), and 76% had increased necrosis (P < .001). Response to
      sunitinib was significantly more favorable (according to MASS criteria) in
      resected than in nonresected tumors (P = .005). In addition, the degree of
      baseline necrosis was less in tumors subsequently resected than in nonresected
      tumors (P = .05). Multivariate analysis showed that higher tumor attenuation
      after 2 cycles of sunitinib therapy and a favorable response (MASS criteria)
      after 2 cycles of sunitinib therapy were independent predictors of subsequent
      tumor resection. CONCLUSION: In unresectable primary RCC tumors, changes in
      select CT parameters after 2 cycles of neoadjuvant sunitinib might be associated
      with the potential for surgical resection.

PMID- 24126240
TI  - L-Methionine inhibits growth of human pancreatic cancer cells.
AB  - We have previously shown that L-methionine inhibits proliferation of breast,
      prostate, and colon cancer cells. This study extends these findings to BXPC-3
      (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the
      reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for
      7 days or for 3 days, followed by 4 days of culture without L-methionine
      (recovery). Cell proliferation, apoptosis, and cell cycle effects were assessed
      by flow cytometry after staining for Ki-67 or annexin V/propidium iodide. Cell
      proliferation was reduced by 31-35% after 7 days of methionine exposure; the
      effect persisted in BXPC-3 and HPAC cells after 4 days of recovery. Methionine
      increased apoptosis by 40-75% in HPAC cells, but not in BXPC-3 cells. Continuous
      exposure to methionine caused accumulation of BXPC-3 cells in the S phase and
      HPAC cells in both the G0/G1 and S phases; however, after 4 days of recovery,
      these effects disappeared. In conclusion, L-methionine inhibits proliferation and
      interferes with the cell cycle of BXPC-3 and HPAC pancreatic cancer cells; the
      effects on apoptosis remarkably persisted after methionine withdrawal. Apoptosis
      was induced only in BXPC-3 cells. Some of the differences in the effects of
      methionine between cell lines may be related to disparate p53 status. These
      findings warrant further studies on the potential therapeutic benefit of L
      methionine against pancreatic cancer. 

PMID- 24126242
TI  - Cooperation promotes the evolution of separate sexes from hermaphrodites with
      unitary growth.
AB  - Most animals have specialized into separate sexes but most plants remain
      hermaphroditic. The underlining cause for this is still unclear. Here we address
      this question by evolutionary stable strategy analysis and exact calculation of
      frequency-dependent selection and genetic drift in geographically structured
      populations. Reproductive investments of hermaphrodites are divided into male and
      female functions, and each sex requires linear investments that increase linearly
      with successful gamete number and reusable investments (RIs) that increase less
      than linearly. Individuals specializing into one sex require RIs of only this sex
      and thus can produce more gametes. However, these gametes suffer strong kin
      competition as they are of the same sex and gamete number of the other sex
      decreases. The success of individuals specializing into one sex requires
      individuals specializing into the other sex to cooperate with them, providing
      them with more opposite-sex gametes and relaxing them of the same-sex
      competition. The evolution of this cooperation does not require two rare
      mutations to happen simultaneously at the same place, because single-sex mutants
      can sparsely spread in a hermaphroditic population with RIs despite genetic drift
      and wait for mutants of the other sex to arise. RI resembles fixed cost in
      previous theories. However, previous theories considered all costs except for
      costs for gametes as fixed costs and this does not capture an important plant
      animal difference; modular growth of sexual organs in most plants and some
      animals promotes reproductive investments to increase linearly with offspring
      number, so their investments in sexual organs are linear investments rather than
      fixed costs. This study shows the evolution of separate sexes from hermaphrodites
      as an example of the evolution of cooperation and mutualism as in harmony games,
      and highlights modular growth as an important factor that prevents most plants
      and some animals from evolving into separate sexes. 

PMID- 24126241
TI  - Enhanced liver autophagic activity improves survival of septic mice lacking
      surfactant proteins A and D.
AB  - Autophagy is a protective cellular mechanism in response to various stresses,
      including sepsis. Sepsis is defined as systemic inflammation by infection.
      Surfactant protein A and D (SP-A and SP-D) are involved in host defense,
      regulation of inflammation, and homeostasis, but their roles in the autophagic
      activity and relevant gene expression in sepsis are unclear. In this study, mice
      lacking SP-A and SP-D (SP-A/D KO mice) and background-matched wild-type (WT)
      C57BL/6 mice underwent either cecal ligation and puncture (CLP) or sham surgery.
      The results showed that SP-A/D KO mice had lower mortality than WT mice in CLP
      sepsis. Liver tissues showed marked pathological changes in both septic SP-A/D KO
      and WT mice 24 hrs after CLP treatment; and quantitative analysis of liver
      histopathology revealed significant difference between septic SP-A/D and septic
      WT mice. SP-A/D KO mice had higher basal and sepsis-induced level of autophagy
      than WT mice (p < 0.05), as judged by Western blot and electron microscopic
      analyses. The expression of 84 autophagy-related genes revealed differential
      basal and sepsis-induced gene expression between SP-A/D KO and WT mice. The
      expression increased in three genes and decreased in four genes in septic WT
      mice, as compared to septic SP-A/D KO mice (p < 0.05). Furthermore, differential
      responses to sepsis between SP-A/D KO and WT mice were found in six signaling
      pathways related to autophagy and apoptosis. Therefore, enhanced autophagic
      activity improves the survival of septic SP-A/D KO mice through the regulation of
      liver autophagy/apoptosis-related gene expression and signaling pathway
      activation. 

PMID- 24126243
TI  - Can front-of-pack labelling schemes guide healthier food choices? Australian
      shoppers' responses to seven labelling formats.
AB  - There is evidence that easily accessible, comprehensible and consistent nutrient
      information on the front of packaged foods could assist shoppers to make
      healthier food choices. This study used an online questionnaire of 4357 grocery
      shoppers to examine Australian shoppers' ability to use a range of front-of-pack
      labels to identify healthier food products. Seven different front-of-pack
      labelling schemes comprising variants of the Traffic Light labelling scheme and
      the Percentage Daily Intake scheme, and a star rating scheme, were applied to
      nine pairs of commonly purchased food products. Participants could also access a
      nutrition information panel for each product. Participants were able to identify
      the healthier product in each comparison over 80% of the time using any of the
      five schemes that provided information on multiple nutrients. No individual
      scheme performed significantly better in terms of shoppers' ability to determine
      the healthier product, shopper reliance on the 'back-of-pack' nutrition
      information panel, and speed of use. The scheme that provided information about
      energy only and a scheme with limited numerical information of nutrient type or
      content performed poorly, as did the nutrition information panel alone (control).
      Further consumer testing is necessary to determine the optimal format and content
      of an interpretive front-of-pack nutrition labelling scheme. 

PMID- 24126244
TI  - Pityriasis rubra pilaris followed by severe herpes simplex 2 infection.

PMID- 24126245
TI  - [Is flu all that which clinically appears as flu?].

PMID- 24126246
TI  - Comparison of arterial and venous whole blood clot initiation, formation, and
      strength by thromboelastography in anesthetized swine.
AB  - Thromboelastography (TEG) analysis was used to determine if differences exist
      between venous and arterial samples in anesthetized swine, using identical
      sampling techniques for each of the samples. We hypothesized that TEG parameters
      would not differ between native whole blood venous and arterial samples. Thirty
      male Landrace swines were included in the study. Both the femoral artery and vein
      were catheterized using standard cut-down techniques and with identically sized
      catheters to rule out any catheter size effects on the results. Standard TEG
      parameters for native whole venous and arterial blood samples (r, K, alpha, MA,
      G, and coagulation index) were measured or calculated, and t-test or Mann-Whitney
      rank-sum test used for comparison when appropriate. Significant differences were
      detected for r (venous < arterial), K (venous < arterial), alpha (venous >
      arterial), and coagulation index (venous > arterial) TEG parameters. No
      significant differences were measured for MA or G. These differences are
      important, especially when temporal changes in TEG are utilized to monitor
      patient stability and fluid therapy protocols using trends in coagulation
      properties. Taken together, these results suggest that clots are more likely to
      form at a faster rate in venous samples compared to arterial samples, but the
      overall clot strength does not differ. Therefore, if TEG analysis is being used
      to monitor coagulation profiles in a patient, care should be taken to use the
      same site and technique if results are to be used for comparative purposes. 

PMID- 24126247
TI  - Combination between mean platelet volume and platelet distribution width to
      predict the prevalence and extent of coronary artery disease: results from a
      large cohort study.
AB  - The aim of the current study was to investigate whether the combination between
      mean platelet volume (MPV) and platelet distribution width (PDW) may improve the
      prognostic information in the prediction of prevalence and extent of coronary
      artery disease (CAD). We measured MPV and PDW in 2330 consecutive patients
      undergoing coronary angiography. Significant CAD was defined as stenosis more
      than 50% in at least one coronary vessel. We additionally measured carotid intima
      media thickness (IMT) in 359 patients. Patients were grouped according to the
      median value of MPV (10.8fl) and PDW (13fl): Group 1 (MPV and PDW < 50th
      percentile; n = 958); Group 2 (MPV or PDW >=50th percentile; n = 288); Group 3
      (MPW and PDW >= 50th percentile; n = 1055). Patients in Group 3 were older (P <
      0.001) with larger prevalence of diabetes (P = 0.024). Combined MPV-PWD was
      significantly associated with baseline glycemia (P < 0.001) and red blood cell
      count (P < 0.0001), but inversely related to platelet count (P < 0.0001).
      Combined MPV-PDW was inversely associated with the presence of thrombus, but
      directly related to the prevalence of chronic occlusion and worse TIMI flow.
      However, combined MPV-MPV was not associated with the prevalence of CAD [odds
      ratio (OR) (95% confidence interval (CI) = 0.99 (0.90-1.09), P = 0.87; adjusted
      OR (95%CI) = 0.95 (0.85-1.05), P = 0.3], or severe CAD [OR (95%CI) = 1.05 (0.95
      1.16), P = 0.3; adjusted OR (95% CI) = 0.97 (0.87-1.08), P = 0.63]. No
      relationship was observed between IMT and the combination of PDW and MPW. This
      study showed that the combined information on MPV and PDW is not related to the
      extent of CAD and carotid IMT. Thus, both MPV and PDW can not be considered as a
      risk factor for CAD. 

PMID- 24126248
TI  - Asymmetrical crying face concomitant with Glanzmann's thrombasthenia.
AB  - We report a case of a 3-month-old Turkish girl who had clinical and laboratory
      features of Glanzmann's thrombasthenia associated with asymmetric crying facies
      (ACF). Although ACF is a minor anomaly, it should not be forgotten that it can be
      accompanied by major congenital anomalies and if this finding is detected, other
      anomalies should be investigated. 

PMID- 24126249
TI  - Correlation between culture-identified bacteria in the middle nasal meatus and CT
      score in patients with chronic rhinosinusitis.
AB  - The aim of this study was to compare bacteriological findings in the middle nasal
      meatus in patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP)
      and without nasal polyps (CRSsNP) and healthy controls, and to investigate the
      correlation between the prevalence of culture-identified bacteria and the
      severity of sinus disease. Bacterial culture was performed using a swab from the
      middle nasal meatus under endoscopic control in 72 patients with CRSwNP, 25
      patients with CRSsNP and 59 healthy controls. Computed tomography (CT) scans were
      graded for severity using the Lund-Mackay scoring system. Patients with more
      severe forms of CRS with and without nasal polyps had significantly higher rates
      of pathogenic bacteria in the middle nasal meatus compared with patients with
      lower CT scores of the paranasal sinuses. There were no significant differences
      in bacterial species among CRSwNP, CRSsNP and control patients. These results
      demonstrate, for the first time, that colonization by pathogenic bacteria in
      patients with CRSwNP and CRSsNP is associated with a more severe form of the
      disease, as assessed by a pre-operative CT scan of the paranasal sinuses. The
      results suggest a role for bacterial infection in the pathogenesis of CRS.
      However, bacteria do not appear to play a role in the development of nasal
      polyposis in patients with CRS. 

PMID- 24126251
TI  - Noise tolerance in a Neocognitron-like network.
AB  - The Neocognitron and its related hierarchical models have been shown to be
      competitive in recognizing handwritten digits and objects. However, the tolerance
      of these models to several types of noise can be low. We will start by briefly
      overviewing some previous results regarding the tolerance of these models.
      Afterwards, we report the higher noise tolerance of the winner-take-all response
      in a hierarchical model over related models. We provide an analysis and
      interpretation of this tolerance under Bayesian decision theory. Finally, we
      report on how to further improve recognition for extremely noisy patterns. 

PMID- 24126252
TI  - Biologically relevant neural network architectures for support vector machines.
AB  - Neural network architectures that implement support vector machines (SVM) are
      investigated for the purpose of modeling perceptual one-shot learning in
      biological organisms. A family of SVM algorithms including variants of maximum
      margin, 1-norm, 2-norm and nu-SVM is considered. SVM training rules adapted for
      neural computation are derived. It is found that competitive queuing memory (CQM)
      is ideal for storing and retrieving support vectors. Several different CQM-based
      neural architectures are examined for each SVM algorithm. Although most of the
      sixty-four scanned architectures are unconvincing for biological modeling four
      feasible candidates are found. The seemingly complex learning rule of a full nu
      SVM implementation finds a particularly simple and natural implementation in
      bisymmetric architectures. Since CQM-like neural structures are thought to encode
      skilled action sequences and bisymmetry is ubiquitous in motor systems it is
      speculated that trainable pattern recognition in low-level perception has evolved
      as an internalized motor programme. 

PMID- 24126250
TI  - Determinants of successful weight loss after using a commercial web-based weight
      reduction program for six months: cohort study.
AB  - BACKGROUND: The Internet is widely available and commonly used for health
      information; therefore, Web-based weight loss programs could provide support to
      large parts of the population in self-guided weight loss. Previous studies showed
      that Web-based weight loss interventions can be effective, depending on the
      quality of the program. The most effective program tools are visual progress
      charts or tools for the self-monitoring of weight, diet, and exercises.
      KiloCoach, a commercial program currently available in German-speaking countries,
      incorporates these features. A previous investigation showed that the program
      effectively supports users in losing weight. OBJECTIVE: We investigated weight
      loss dynamics stratified by weight loss success after 6-month use of KiloCoach.
      Furthermore, we analyzed possible associations between intensity of program use
      and weight loss. The results are intended for tailoring user recommendations for
      weight-loss Internet platforms. METHODS: Datasets of KiloCoach users (January 1,
      2008 to December 31, 2011) who actively used the platform for 6 months or more
      were assigned to this retrospective analysis. Users (N=479) were 42.2% men, mean
      age of 44.0 years (SD 11.7), with a mean body mass index (BMI) of 31.7 kg/m2 (SD
      3.2). Based on the weight loss achieved after 6 months, 3 success groups were
      generated. The unsuccessful group lost <5%, the moderate success group lost 5%
      9.9%, and the high success group lost >=10% of their baseline body weight. At
      baseline, the unsuccessful (n=261, 54.5%), moderate success (n=133, 27.8%), and
      high success (n=85, 17.8%) groups were similar in age, weight, BMI, and gender
      distribution. RESULTS: After 6 months, the unsuccessful group lost 1.2% (SD 2.4),
      the moderate success group lost 7.4% (SD 1.5), and the high success group lost
      14.2% (SD 3.8) of their initial weight (P<.001). Multivariate regression showed
      that early weight loss (weeks 3-4), the total number of dietary protocols, and
      the total number of weight entries were independent predictors for 6-month weight
      reduction (all P<.001) explaining 52% of the variance in weight reduction.
      Sensitivity analysis by baseline carried forward method confirmed all independent
      predictors of 6-month weight loss and reduced the model fit by only 11%. The high
      success group lost weight faster and maintained weight loss more efficiently than
      the other groups (P<.001). Early weight loss was associated with weight
      maintenance after 1 year and 2 years (both P<.001). Weight dynamics did not
      differ between men and women over 6 months when adjusted for baseline and usage
      parameters (P=.91). The percentage of male long-term users was unusually high
      (42.2%). CONCLUSIONS: Our results suggest that early weight loss and close
      program adherence (ie, 5 dietary protocols per week and weekly entering of
      current weight), especially in the early phase of program usage, can improve
      weight loss outcome.

PMID- 24126253
TI  - Short-term and long-term outcomes of serial robotic training for improving upper
      limb function in chronic stroke.
AB  - The aim of this study was to determine short-term and long-term changes in motor
      function in patients with chronic hemiparesis who underwent robot training and to
      evaluate its long-term benefit after 6 months. This was a longitudinal study with
      a 6-month follow-up. The 15 patients included in this study underwent the Fugl
      Meyer test, the Ashworth Scale test, the Frenchay Arm test, and the Box and Block
      test according to the following schedule: immediately before (T1, T3) and after
      each treatment (T2, T4), and 6 months after T4 (T5). There were statistically
      significant improvements in Fugl-Meyer test between T1 and T2 and between T1 and
      T4; the score increased in the Ashworth Scale test for Shoulder between T1 and T3
      and between T1 and T5; a statistically significant decrease was found between T1
      and T2 and between T1 and T4, in the Box and Block test between T1 and T4, and
      also between T1 and T5. This original rehabilitation treatment may contribute
      toward increasing upper limb motor recovery in stable chronic stroke patients. 

PMID- 24126254
TI  - Recent trends for practical rehabilitation robotics, current challenges and the
      future.
AB  - This paper presents and studies various selected literature primarily from
      conference proceedings, journals and clinical tests of the robotic, mechatronics,
      neurology and biomedical engineering of rehabilitation robotic systems. The
      present paper focuses of three main categories: types of rehabilitation robots,
      key technologies with current issues and future challenges. Literature on
      fundamental research with some examples from commercialized robots and new robot
      development projects related to rehabilitation are introduced. Most of the
      commercialized robots presented in this paper are well known especially to
      robotics engineers and scholars in the robotic field, but are less known to
      humanities scholars. The field of rehabilitation robot research is expanding; in
      light of this, some of the current issues and future challenges in rehabilitation
      robot engineering are recalled, examined and clarified with future directions.
      This paper is concluded with some recommendations with respect to rehabilitation
      robots. 

PMID- 24126256
TI  - Source time function properties indicate a strain drop independent of earthquake
      depth and magnitude.
AB  - The movement of tectonic plates leads to strain build-up in the Earth, which can
      be released during earthquakes when one side of a seismic fault suddenly slips
      with respect to the other. The amount of seismic strain release (or 'strain
      drop') is thus a direct measurement of a basic earthquake property, that is, the
      ratio of seismic slip over the dimension of the ruptured fault. Here the analysis
      of a new global catalogue, containing ~1,700 earthquakes with magnitude larger
      than 6, suggests that strain drop is independent of earthquake depth and
      magnitude. This invariance implies that deep earthquakes are even more similar to
      their shallow counterparts than previously thought, a puzzling finding as shallow
      and deep earthquakes are believed to originate from different physical
      mechanisms. More practically, this property contributes to our ability to predict
      the damaging waves generated by future earthquakes. 

PMID- 24126255
TI  - Developmental exposure to valproic acid alters the expression of microRNAs
      involved in neurodevelopment in zebrafish.
AB  - Congenital malformations are a prevalent cause of infant mortality in the United
      States and their induction has been linked to a variety of factors, including
      exposure to teratogens. However, the molecular mechanisms of teratogenicity are
      not fully understood. MicroRNAs are an important group of small, non-coding RNAs
      that regulate mRNA expression. MicroRNA roles in early embryonic development are
      well established, and their disruption during development can cause
      abnormalities. We hypothesized that developmental exposure to teratogens such as
      valproic acid alters microRNA expression profiles in developing embryos. Valproic
      acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy,
      bipolar disorder and migraines. To examine the effects of valproic acid on
      microRNA expression during development, we used zebrafish embryos as a model
      vertebrate developmental system. Zebrafish embryos were continuously exposed to
      valproic acid (1mM) or vehicle control (ethanol) starting from 4h post
      fertilization (hpf) and sampled at 48 and 96hpf to determine the miRNA expression
      profiles prior to and after the onset of developmental defects. At 96hpf, 95% of
      the larvae showed skeletal deformities, abnormal swimming behavior, and
      pericardial effusion. Microarray expression profiling was done using Agilent
      zebrafish miRNA microarrays. Microarray results revealed changes in miRNA
      expression at both time points. Thirteen miRNAs were differentially expressed at
      48hpf and 22 miRNAs were altered at 96hpf. Among them, six miRNAs (miR-16a, 18c,
      122, 132, 457b, and 724) were common to both time points. Bioinformatic target
      prediction and examination of published literature revealed that these miRNAs
      target several genes involved in the normal functioning of the central nervous
      system. These results suggest that the teratogenic effects of valproic acid could
      involve altered miRNA expression. 

PMID- 24126258
TI  - Adnexal torsion: review of the literature.
AB  - Adnexal torsion is one of a few gynecologic surgical emergencies. Misdiagnosis or
      delay in treatment can have permanent sequelae including loss of an ovary with
      effect on future fertility, peritonitis, and even death. A PubMed search was
      performed between 1985 and 2012 for reviews, comparative studies, and case
      reports to provide a review of the epidemiology, risk factors, clinical
      presentation, common laboratory and imaging findings, and treatments of adnexal
      torsion. Common symptoms of torsion include pain, nausea, and vomiting, with
      associated abdominal or pelvic tenderness, and may differ in premenarchal and
      pregnant patients. Laboratory and imaging findings including ultrasound with
      Doppler analysis, computed tomography, and magnetic resonance imaging can assist
      in making the diagnosis but should not trump clinical judgment; normal Doppler
      flow can be observed in up to 60% of adnexal torsion cases. Treatment depends on
      the individual patient but commonly includes detorsion, even if the adnexae
      initially seem necrotic, with removal of any associated cysts or salpingo
      oophorectomy, because recurrence rates are higher with detorsion alone or
      detorsion with only cyst aspiration. 

PMID- 24126257
TI  - The use of barbed suture for laparoscopic hysterectomy and myomectomy: a
      systematic review and meta-analysis.
AB  - We conducted a meta-analysis comparing the efficacy of laparoscopic suturing with
      or without barbed suture for myomectomy or hysterectomy. We used a systematic
      electronic search strategy of published literature using the following databases:
      Cochrane Database of Systematic Reviews, MEDLINE, Embase, and OVID MEDLINE In
      Process & Other Non-Indexed Citations databases. The following medical subject
      heading terms, key words, and their combinations were used: laparoscopy,
      myomectomy, hysterectomy, and barbed suture. Studies in which women undergoing
      laparoscopic myomectomy or hysterectomy using barbed suture or conventional
      suture were selected. The main outcome measures chosen for the current meta
      analysis were operative time, suturing time, estimated blood loss or change in
      hemoglobin level, and degree of suturing difficulty. The results of the meta
      analysis studies were expressed as the standardized mean difference (SMD) with
      95% confidence intervals (CIs). Compared with the use of conventional suture, the
      total operative time of laparoscopic myomectomy (SMD = -0.58; 95% CI, -0.88 to 
      0.28) and the suturing time to close the uterine incision (SMD = -1.38; 95% CI, 
      1.86 to -0.90) were significantly reduced with the use of barbed suture. Meta
      analysis on laparoscopic hysterectomy shows that the time to suture the vaginal
      vault, the total operative time, and the estimated blood loss were comparable
      with or without the use of barbed suture. The degree of suturing difficulty was
      reported in 2 randomized trials. Compared with the use of conventional suture,
      the degree of suturing difficulty was lower with the use of barbed suture (SMD = 
      1.39; 95% CI, -1.83 to -0.95). The use of barbed suture facilitates laparoscopic
      suturing of myomectomy incision and closure of the vaginal vault. Its use is
      associated with a reduced operative time of laparoscopic myomectomy.

PMID- 24126259
TI  - Ultrasound-guided reoperative hysteroscopy for managing global endometrial
      ablation failures.
AB  - STUDY OBJECTIVE: To determine whether ultrasound-guided reoperative hysteroscopy
      can reduce the need for hysterectomy in women experiencing delayed complications
      after global endometrial ablation (GEA) procedures. DESIGN: Retrospective review
      (Canadian Task Force classification III). SETTING: Private physician's office.
      PATIENTS: Fifty women who had experienced a delayed complication after a GEA
      procedure were referred to the author's private practice. INTERVENTION: All 50
      women underwent ultrasound-guided reoperative hysteroscopy in which the uterine
      cavity was fully explored and areas of endometrial growth and other disease were
      identified and excised. MEASUREMENTS AND MAIN RESULTS: Intraoperative
      complications, patient satisfaction, and avoidance of hysterectomy were
      determined. There were no intraoperative or postoperative complications. The mean
      duration of follow-up was 18.1 months (95% confidence interval, 13.8-22.4). Forty
      four of 49 patients (88.9%) were satisfied with the outcome, and further surgery
      was not necessary during the study period. CONCLUSION: Ultrasound-guided
      reoperative hysteroscopy is a safe and effective minimally invasive treatment for
      management of delayed complications after GEA procedures.

PMID- 24126260
TI  - Effect of surgery for endometrioma on ovarian function.
AB  - Endometriosis affects a significant proportion of reproductive-aged women. The
      impact of the disease on ovarian function is an important consideration when
      planning treatment in women who want to retain the potential of future
      childbearing. This review will specifically address the association between
      endometriomas and diminished ovarian reserve, with a particular focus on the
      impact of surgical endometrioma resection on ovarian function. The existing
      literature supports an adverse effect of ovarian endometriomas on spontaneous
      ovulation rates, markers of ovarian reserve, and response to ovarian stimulation,
      although data on clinical pregnancy and live birth rates remain inconsistent.
      Surgical removal of endometriomas may worsen ovarian function by removing healthy
      ovarian cortex or compromising blood flow to the ovary. It is evident that
      surgical excision of endometriomas acutely impairs ovarian function as measured
      by ovarian reserve markers; whether this represents progressive or long term
      impairment remains the subject of ongoing investigation. 

PMID- 24126261
TI  - Hysteroscopic sterilization: 10-year retrospective analysis of worldwide
      pregnancy reports.
AB  - STUDY OBJECTIVE: To identify factors that might contribute to pregnancies
      reported after hysteroscopic sterilization worldwide. DESIGN: Retrospective
      review of commercial data compiled from the MAUDE database, medical literature,
      and manufacturer reports received during commercial distribution of hysteroscopic
      sterilization micro-inserts from 2001 through 2010 (Canadian Taskforce
      classification III descriptive study). MEASUREMENTS AND MAIN RESULTS: From 2001
      through 2010, 497 305 hysteroscopic sterilization kits were distributed
      worldwide, and 748 pregnancies were reported, i.e., 0.15% of the estimated user
      population based on the number of distributed kits. The data were sufficient to
      enable analysis of 508 pregnancies for potential contributing factors and showed
      most to be associated with patient or physician noncompliance (n = 264) or
      misinterpreted confirmation tests (n = 212). Conceptions deemed to have occurred
      within 2 weeks of the procedure and therefore too early for detection were
      identified in 32 cases. CONCLUSION: Although there are limitations to the dataset
      and the study design is retrospective, it represents the largest body of
      cumulative hysteroscopic sterilization data available to date. Of the 748
      pregnancies reported, it is apparent that some might have been prevented with
      greater patient and clinician attention to interim contraceptive use and
      counseling and with more rigorous evaluation and informed interpretation of the
      procedure confirmation tests. Although the estimated pregnancy rate based on such
      a dataset is likely an underestimation, it does suggest that the evaluable field
      performance of hysteroscopic sterilization micro-inserts is consistent with the
      labeled age-adjusted effectiveness of 99.74% at 5 years.

PMID- 24126262
TI  - Failure of the Laryngeal Mask Airway UniqueTM and ClassicTM in the pediatric
      surgical patient: a study of clinical predictors and outcomes.
AB  - BACKGROUND: Although predictors of laryngeal mask airway failure in adults have
      been elucidated, there remains a paucity of data regarding laryngeal mask airway
      failure in children. METHODS: The authors performed a retrospective database
      review of all pediatric patients who received a laryngeal mask anesthetic at
      their institution from 2006 to 2010. Device brands were restricted to LMA
      UniqueTM (Cardinal Health, Dublin, OH) and LMA ClassicTM (LMA North America, San
      Diego, CA), and primary outcome was laryngeal mask failure, defined as any airway
      event requiring device removal and tracheal intubation. Potential risk factors
      were analyzed with both univariate and multivariate techniques and included
      medical history, physical examination, surgical, and anesthetic characteristics.
      RESULTS: Of the 11,910 anesthesia cases performed in the study, 102 cases (0.86%)
      experienced laryngeal mask failure. Common presenting features of laryngeal mask
      failures included leak (25%), obstruction (48%), and patient intolerance such as
      intractable coughing/bucking (11%). Failures occurred before incision in 57% of
      cases and after incision in 43%. Independent clinical associations included
      ear/nose/throat surgical procedure, nonoutpatient admission status, prolonged
      surgical duration, congenital/acquired airway abnormality, and patient transport.
      CONCLUSIONS: The findings of the study support the use of the LMA UniqueTM and
      LMA ClassicTM as reliable pediatric supraglottic airway devices, demonstrating
      relatively low failure rates. Predictors of laryngeal mask airway failure in the
      pediatric surgical population do not overlap with those in the adult population
      and should therefore be independently considered.

PMID- 24126263
TI  - Immobilization with atrophy induces de novo expression of neuronal nicotinic
      alpha7 acetylcholine receptors in muscle contributing to neurotransmission.
AB  - BACKGROUND: Mature acetylcholine receptor (AChR) isoform normally mediates muscle
      contraction. The hypothesis that alpha7AChRs up-regulate during immobilization
      and contribute to neurotransmission was tested pharmacologically using specific
      blockers to mature (waglerin-1), immature (alphaA-OIVA), and alpha7AChRs
      (methyllycaconitine), and nonspecific muscle AChR antagonist, alpha-bungarotoxin.
      METHODS: Mice were immobilized; contralateral limbs were controls. Fourteen days
      later, anesthetized mice were mechanically ventilated. Nerve-stimulated tibialis
      muscle contractions on both sides were recorded, and blockers enumerated above
      sequentially administered via jugular vein. Data are mean +/- standard error.
      RESULTS: Immobilization (N = 7) induced tibialis muscle atrophy (40.6 +/- 2.8 vs.
      52.1 +/- 2.0 mg; P < 0.01) and decrease of twitch tension (34.8 +/- 1.1 vs. 42.9
      +/- 1.5 g; P < 0.01). Waglerin-1 (0.3 +/- 0.05 MUg/g) significantly (P = 0.001; N
      = 9) depressed twitch tension on contralateral (>=97%) versus immobilized side
      (approximately 45%). Additional waglerin-1 (total dose 1.06 +/- 0.12 MUg/g or
      approximately 15.0 * ED50 in normals) could not depress twitch of 80% or greater
      on immobilized side. Immature AChR blocker, alphaA-OIVA (17.0 +/- 0.25 MUg/g) did
      not change tension bilaterally. Administration of alpha-bungarotoxin (N = 4) or
      methyllycaconitine (N = 3) caused 96% or greater suppression of the remaining
      twitch tension on immobilized side. Methyllycaconitine, administered first (N =
      3), caused equipotent inhibition by waglerin-1 on both sides. Protein expression
      of alpha7AChRs was significantly (N = 3; P < 0.01) increased on the immobilized
      side. CONCLUSIONS: Ineffectiveness of waglerin-1 suggests that the twitch tension
      during immobilization is maintained by receptors other than mature AChRs. Because
      alphaA-OIVA caused no neuromuscular changes, it can be concluded that immature
      AChRs contribute minimally to neurotransmission. During immobilization
      approximately 20% of twitch tension is maintained by up-regulation of alpha
      bungarotoxin- and methyllycaconitine-sensitive alpha7AChRs.

PMID- 24126265
TI  - Equivalent efficacy of hydroxyethyl starch 130/0.4 and human serum albumin: if
      nothing is the same, is everything different? The importance of context in
      clinical trials and statistics.

PMID- 24126266
TI  - Effect of rest duration on recovery from repeated exercise in near-market-weight
      pigs.
AB  - The process of transportation can be seen as a succession of stressors, from
      which pigs may not have time to recover before slaughter. The aim of this study
      was to determine the extent to which the duration of the rest time given to near
      market-weight pigs after an initial exposure to exercise affected their recovery
      from subsequent exercise. Eighteen groups of 3 gilts were exercised (Ex1) through
      a standard handling course, including two 19 degrees  ramps, and then were held
      in a holding pen for either 35 (RT35), 75 (RT75), or 150 (RT150) min (Rest Period
      1, RP1). Afterward, pigs were exercised a second time (Ex2) and left to rest for
      150 min. Recovery from Ex2 (Rest Period 2, RP2) was assessed using measures of
      heart rate (HR), respiratory rate (RR), skin temperature (ST), and posture.
      Repeated measures and regression analysis were used to analyze the data. For RT75
      pigs, there were no detrimental effects of Ex2 on HR, RR, and handling time (P >
      0.05, for all) during the exercise and recovery periods. Skin temperature during
      Ex2 was greater than ST during Ex1 (P < 0.001), whereas ST during RP1 did not
      differ from ST during RP2 (P > 0.05). Doubling the rest period did not provide
      any more beneficial effects in regard to RR and HR (P > 0.05 for both) during Ex2
      and RP2 compared to RT75 pigs, as shown by the similar latencies to recover for
      these 2 variables. However, ST did not increase between exercises, and RT150 pigs
      required less time to complete the handling course during Ex2. The results show
      that a lack of rest after an initial exposure to exercise made pigs more
      susceptible to stress during Ex2 and RP2, as demonstrated by greater (P < 0.001
      for all) HR, RR, and ST during RP2 compared to RP1 and Ex2 compared to Ex1. When
      given more than 35 min to rest during RP2, RT35 pigs eventually recovered.
      Latencies of recovery for HR, ST, RR, and posture were all greater (P < 0.05 for
      HR, ST, and RR and P < 0.001 for posture) than those obtained for RT75 and RT150
      pigs. This study highlights that if pigs are not initially given enough rest to
      recover from exercise, a subsequent exposure to the same exercise will cause an
      increase in these physiological variables during exercise and recovery. Further
      research is needed to investigate factors contributing to the quality of rest,
      with a particular focus on conditions not allowing a proper rest on the truck or
      in lairage. 

PMID- 24126267
TI  - Changes in gut microbial populations, intestinal morphology, expression of tight
      junction proteins, and cytokine production between two pig breeds after challenge
      with Escherichia coli K88: a comparative study.
AB  - This study hypothesized that the gut microbial populations, intestinal
      morphology, and cytokine production are differentially altered in 2 different pig
      breeds, namely, Chinese native Jinhua pigs and European Landrace pigs, after
      orally challenge with enterotoxigenic Escherichia coli (ETEC) K88. A total of 12
      Jinhua pigs and 12 Landrace pigs were allocated to either the nonchallenged or
      the challenged groups (6 pigs per group). The challenged pigs were orally
      administered ETEC K88, and their nonchallenged counterparts were given sterile
      Luria-Bertani broth. Selected gut microbial populations, intestinal morphology,
      mRNA expression of tight junction proteins, and the levels of ileal cytokines and
      secretory immunoglobulin A (sIgA) production were measured in Jinhua and Landrace
      pigs. The results showed that the challenged Jinhua pigs exhibited a
      significantly (P < 0.05) lower incidence of diarrhea compared with their Landrace
      counterparts. The Escherichia coli (E.coli) population and the percentage of E.
      coli in the total bacteria population were increased in response to ETEC K88
      challenge in both Jinhua and Landrace pigs. The challenged Landrace pigs shed
      more E. coli (P < 0.05) and had higher percentage of E. coli in the total
      bacteria population in the colon (P < 0.05) compared with their Jinhua
      counterparts. Both pig breeds tended to exhibit greater villous atrophy and crypt
      depth reduction in all of the intestinal segments with challenge. The expression
      of tight junction proteins decreased in response to ETEC K88 challenge in both
      pig breeds. The levels of the proinflammatory cytokines interferon (IFN)-gamma,
      tumor necrosis factor-alpha, and IL-6 and the secretion of sIgA were positively
      altered whereas the levels of the anti-inflammatory cytokine IL-4 and
      transforming growth factor (TGF)-beta were negatively altered by ETEC K88
      challenge in both breeds. Jinhua pigs exhibited significantly higher levels of
      IFN-gamma and TGF-beta (P < 0.05) in the challenged group. Our findings provide
      valuable evidence to explain the differences in the intestinal physiology between
      Jinhua and Landrace pigs; that is, Jinhua pigs appeared to show better growth
      performance, a lower incidence of diarrhea, and a lower extent of immune
      activation in response to ETEC K88 challenge and a higher Lactobacillus
      population, a higher percentage of Lactobacillus in the total bacteria
      population, a higher ratio of Lactobacillus to E. coli, and higher levels of
      tight junction proteins with and without challenge. 

PMID- 24126264
TI  - Perioperative organ injury.
AB  - Despite the fact that a surgical procedure may have been performed for the
      appropriate indication and in a technically perfect manner, patients are
      threatened by perioperative organ injury. For example, stroke, myocardial
      infarction, acute respiratory distress syndrome, acute kidney injury, or acute
      gut injury are among the most common causes for morbidity and mortality in
      surgical patients. In the current review, the authors discuss the pathogenesis of
      perioperative organ injury, and provide select examples for novel treatment
      concepts that have emerged over the past decade. Indeed, the authors are of the
      opinion that research to provide mechanistic insight into acute organ injury and
      identification of novel therapeutic approaches for the prevention or treatment of
      perioperative organ injury represent the most important opportunity to improve
      outcomes of anesthesia and surgery. 

PMID- 24126268
TI  - Assessment of gastrointestinal permeability by lactulose test in sheep after
      repeated indomethacin treatment.
AB  - The aim of the study was to assess the small intestine permeability by using
      lactulose as a sugar probe and blood metabolites in sheep after a challenge with
      repeated indomethacin injections. According to a changeover design, 7 adult sheep
      (4 males and 3 females) were subjected to 4 intramuscular injections (every 12 h)
      of saline [control (CRT); 7 animals] or indomethacin (INDO; 7 animals). Two hours
      after the last injection, 30 g of lactulose were administered orally to both CTR
      and INDO. Blood samples were collected daily for the analysis of the metabolic
      profile and 5 samples were collected at 2-h intervals following lactulose
      ingestion to monitor changes in blood levels of lactulose as an index of
      intestinal permeability. The INDO challenge induced clinical symptoms such as
      lack of appetite, dullness, weakness, depression, and diarrhea with traces of
      blood in the feces. In INDO group, haptoglobin and ceruloplasmin increased (P <
      0.01) after INDO challenge whereas a decrease (P < 0.05) of negative acute phase
      reactants (e.g., cholesterol, albumin, and paraoxonase) was observed. Reactive
      oxygen metabolites increased (P < 0.01) from 60 to 204 h after the INDO challenge
      start, with a decrease of vitamin E concentration from 12 (P < 0.01) to 132 h (P
      < 0.05). Blood lactulose concentrations were increased (P < 0.05) in INDO animals
      and the highest mean values (17.67 ug/mL in INDO vs. 0.17 ug/mL in CRT; P < 0.01)
      were observed 6 h after oral dosage of lactulose. These changes indicate that the
      INDO challenge led to severe inflammatory responses with oxidative stress by
      enhancing small intestinal permeability in sheep that allowed lactulose to enter
      in blood. The results of this experiment demonstrate that lactulose can be used
      as a probe to assess gastrointestinal permeability in adult ruminants to test the
      consequences of stressing conditions on animal welfare. For this purpose, the
      most suitable time for blood sampling is between 2 and 8 h after the oral dosage
      of lactulose. 

PMID- 24126269
TI  - Physiological, behavioral, and serological responses of horses to shaded or
      unshaded pens in a hot, sunny environment.
AB  - Housing recommendations for horses invariably include providing access to shade
      on hot, sunny days, but the potential benefits have not been scientifically
      studied. This experiment measured physiological, behavioral, and serological
      responses of horses confined individually to completely shaded (SH) or completely
      unshaded (SUN) drylot pens during the summer in Davis, CA. Twelve healthy adult
      horses in a crossover design experienced both treatments for 5 d each. Rectal
      temperature, respiration rate, skin temperature, and sweat scores were recorded
      hourly from 1230 to 1730 h daily. Observations were recorded from 1200 to 1800 h
      for proximity to water, foraging, locomotion, and insect avoidance behaviors.
      Daily blood samples were obtained to measure cortisol, hematocrit, and neutrophil
      to-lymphocyte ratio. Automated and handheld sensors were used to record
      environmental conditions. The mean ambient temperature from 1200 to 1800 h during
      the study was 30.6  degrees C. Rectal temperature was greater for horses in SUN
      than for SH (mean 37.8  degrees C and 37.5  degrees C, respectively, SE = 0.06, P
      = 0.002) as was respiration rate (25.5 and 20.5 breaths/min, SE = 1.3, P =
      0.008), and skin temperature (35.6  degrees C and 34.6  degrees C, SE = 0.1, P <
      0.001). Horses in SUN showed sweat in 51.4% of observations vs. 1.1% for horses
      in SH. Horses in SUN spent more time than SH horses standing near their water
      source (34.0% of observations vs. 20.2%, SE = 0.3, P = 0.004). No differences
      were observed for foraging, locomotion, or insect avoidance behavior (P > 0.05).
      Cortisol concentrations were greater in SUN than SH (3.4 and 2.6 MUg/dL,
      respectively, P < 0.001) but remained within the normal range for resting horses.
      No treatment differences were observed for hematocrit or neutrophil-to-lymphocyte
      ratio (P > 0.05). Horses exhibited treatment differences in the physiological
      measures first, most notably in rectal temperature at 1230 h, corresponding to
      peak solar radiation. Behavioral responses followed these physiological changes,
      with treatment differences in time standing near water becoming apparent at 1400
      h as ambient and black globe temperature increased. Our results indicate that
      both the SH and SUN treatment groups exhibited thermoregulatory responses to
      these summer conditions and horses benefited from shade, as it mitigated these
      physiological and behavioral changes. These results are applicable in developing
      best management practices for the care of domestic horses.

PMID- 24126270
TI  - Predicted high-performing piglets exhibit more and larger skeletal muscle fibers.
AB  - Postnatal (muscle) growth potential in pigs depends on the total number and
      hypertrophy of myofibers in skeletal muscle tissue. In a previous study an
      algorithm was developed to predict piglet BW at the end of the nursery period (10
      wk of age) on the basis of BW at birth, at weaning, and at 6 wk of age. The
      objective of this study was to determine whether the differences in growth
      performance between poor (PP) and high (HP) performing piglets could be the
      result of different skeletal muscle properties. Therefore, from a total of 368
      piglets (offspring from Hypor sows bred to TOPIGS sires) 2 groups with a
      divergent growth performance were selected at 6 wk of age: HP (n = 20, predicted
      BW at 10 wk of age 26.8-30.9 kg) and PP (n = 20, predicted BW at 10 wk of age
      16.0-22.9 kg). Piglets were euthanized at 10 wk of age, and samples of the
      semitendinosus muscle (STN) were collected for histochemistry and gene expression
      analysis using quantitative PCR (qPCR). At 10 wk of age, realized BW did not
      differ from predicted BW in either group (P > 0.880). The HP piglets exhibited
      greater ADG and ADFI from 6 to 10 wk and greater BW at birth and 6 and 10 wk of
      age (P <= 0.002) compared with the PP piglets, whereas G:F ratio was similar (P =
      0.417). Superior growth performance of HP piglets was associated with a 1.27-fold
      higher IGF1 plasma concentration at 10 wk compared with the PP piglets (P =
      0.044). The greater weight and muscle cross-sectional area of STN in HP piglets
      was due to a 1.20-fold increase in total muscle fiber number (TFN; P = 0.009) and
      1.34-fold increase in fiber cross-sectional area (FCSA; P = 0.004) compared with
      the PP piglets. The number of myonuclei per red and intermediate fiber was
      greater in HP piglets (P <= 0.097), but the nucleus-to-cytoplasm ratio was
      unaffected by the performance group (P = 0.861). The mRNA expression of
      proliferating cell nuclear antigen (PCNA), paired box 7 (PAX7), myogenic factor 5
      (MYF5), and myogenic differentiation factor (MYOD) did not differ between groups
      (P >= 0.327). However, IGF2-specific mRNA expression was numerically higher in
      the HP piglets (P = 0.101). The greater myofiber number, the higher degree of
      myofiber hypertrophy, and the increased muscular mRNA expression of IGF2 indicate
      that HP piglets exhibit a greater capacity for lean accretion and may grow faster
      until market weight. In summary, pigs that were selected for predicted high BW at
      10 wk of age using a complex selection model had a superior muscularity in terms
      of greater TFN and FCSA, which may be of advantage for lean mass accretion in
      later life and for meat quality. 

PMID- 24126271
TI  - Eating quality of beef from free-range and confined Podolian young bulls.
AB  - The purpose of the present study was to assess the effect of grazing on meat
      quality of young Podolian bulls by using 6 free-ranging (FR) and 6 confined (CON)
      animals slaughtered at 18 mo of age (Exp. 1). A second experiment (Exp. 2) was
      performed the subsequent year where the age at slaughter was 15 mo of age (6
      animals/group). Quantitative descriptive sensory analysis, water-holding capacity
      (WHC; thawing, centrifugation, and cooking losses), and shear force (only in Exp.
      2) were evaluated on LM, aged 8 d. Both experiments showed that CON animals
      produced beef with greater overall beef flavor (P < 0.01 and P < 0.05 in Exp. 1
      and 2, respectively) and odor intensities (P < 0.10 and P < 0.05 in Exp. and 1
      and 2, respectively) and increased malondialdehyde contents (P < 0.01 and P <
      0.05 in Exp. 1 and 2, respectively). In Exp. 2 beef from FR bulls showed higher
      sensory tenderness as compared with CON bulls (P < 0.05) and a lower shear force
      (P < 0.05). In Exp. 1, beef obtained from FR bulls showed lower centrifugation
      and greater thawing losses compared with samples from bulls from group CON (P <
      0.05) whereas rearing system did not affect any WHC variables in Exp. 2. The
      results obtained from the 2 experiments were generally consistent. The different
      results occasionally observed (e.g., sensory tenderness and WHC) is attributed to
      the different ages at slaughter used in the 2 experiments (18 and 15 mo). In
      particular, at an earlier age at slaughter (15 mo) the effect of FR on meat
      quality was beneficial on sensory tenderness and mechanical properties.
      Therefore, given the additional costs of maintaining the bulls for another 3 mo
      when slaughtered at 18 mo of age, a reduced age at slaughter of FR bulls may be
      suggested to avoid the decrement of herbage mass availability inducing the
      consumption of high amounts of concentrate. 

PMID- 24126272
TI  - Postgraze assessment of toxicosis symptoms for steers grazed on toxic endophyte
      infected tall fescue pasture.
AB  - A 2-yr pen experiment was conducted using 12 different crossbred Angus steers
      each year to determine if short-term changes in prolactin concentrations, body
      temperature, and vasoconstriction reflect recovery from fescue toxicosis after
      steers that previously grazed toxic endophyte (Neotyphodium coenophialum)
      infected Kentucky 31 tall fescue [Lolium arundinaceum (Schreb.) Darbysh] are
      placed on nontoxic feed. Groups of 6 steers from toxic endophyte-infected and
      endophyte-free tall fescue grazing treatments were blocked by BW for assignment
      to pens as a randomized complete block design with 2 replications. Two
      environments were implemented by initiating the experiment on 18 August in yr 1
      and on 8 September in yr 2 for durations of 30 and 21 d, respectively. Rectal
      temperatures were recorded, jugular blood was collected for assaying serum
      prolactin, and cross sections of the caudal artery were ultrasonically imaged at
      selected time points to evaluate temporal changes in the response variables.
      Rectal temperatures in steers on the toxic endophyte pasture treatment declined
      (P < 0.05) linearly over time in yr 1 and 2 and were similar (P > 0.10) to those
      on endophyte-free treatment on d 30 in yr 1 and by d 15 in yr 2. Prolactin
      concentrations in steers on the toxic endophyte pasture treatment showed
      curvilinear increases (P < 0.05) over time and were similar (P > 0.10) to steers
      on the endophyte-free treatment by d 15 in yr 1 and by d 10 in yr 2. Luminal
      areas of the caudal artery in toxic endophyte steers were less (P < 0.05) than
      those in endophyte-free steers across all dates in both years. Results indicated
      that rectal temperatures in steers after they are removed from toxic fescue may
      decrease over time, but temporal changes in rectal temperatures could be affected
      more by prevailing ambient temperatures than by actual mitigation of fescue
      toxicosis. Prolactin concentrations in steers after they are removed from toxic
      endophyte tall fescue can increase and stabilize in less than 2 wk, but alkaloid
      induced vasoconstriction that causes a vulnerability to severe heat stress is not
      alleviated within 30 d. 

PMID- 24126273
TI  - Estimating the comparative clinical and economic consequences of tulathromycin
      for treatment of present or anticipated outbreaks of bovine respiratory disease
      in feedlot cattle in the United States.
AB  - The goal of this study was to determine the clinical and economic impact of using
      tulathromycin as first line treatment for bovine respiratory disease (BRD)
      compared with other commonly used antimicrobials. Two decision trees were
      developed simulating the consequences of treating cattle at high risk of
      developing BRD [control model (CM)] or cattle with first clinical BRD episode
      [treatment model (TM)]. As comparators florfenicol and tilmicosin were considered
      in both models whereas enrofloxacin was included in the TM because it was only
      labeled for treatment of BRD at the time of development of the calculators. A
      total of 5 (CM) and 10 (TM) comparative clinical studies that reported efficacy
      data for the selected drugs and indications were identified as suitable for model
      population. The following outcomes were considered: first treatment success,
      number of subsequent BRD treatments, chronics, and mortalities. Cost parameters
      were considered from the perspective of the producer and included treatment costs
      (first treatment and retreatments) and costs of chronics and deaths derived from
      published sources for 2010 (default). The models allowed the estimation of
      clinical and economic consequences according to each individual trial outcomes.
      Treatment with tulathromycin resulted in more first treatment successes and fewer
      removals (chronics and deaths) in all comparisons. The average total number of
      antimicrobial treatments required for the management of BRD was also least with
      tulathromycin as first treatment option. Because of better efficacy, total costs
      over the entire study periods were always lowest with tulathromycin. Depending on
      the study selected as the basis for the efficacy evaluation, cost savings with
      tulathromycin were calculated in the CM between US$21.00 and $47.86 (vs.
      florfenicol) and $11.37 and $72.64 (vs. tilmicosin); cost savings in the TM
      ranged between $28.47 and $143.87 (vs. florfenicol) and $7.75 and $84.91 (vs.
      tilmicosin) as well as between $23.22 and $47.82 (vs. enrofloxacin), with the
      ranges reflecting a variety of settings in different trials. Thus, the higher
      drug costs of tulathromycin were more than offset by reduced BRD treatments,
      chronics, and mortalities in the herd. Fewer BRD episodes in cattle treated with
      tulathromycin not only contributes to overall savings in BRD management but also
      reduces the necessity of repeated antibiotic treatment, supporting prudent use of
      antimicrobials in livestock. 

PMID- 24126274
TI  - Impact of tylosin phosphate and distillers dried grains with solubles on energy
      and nutrient digestibility and flow through the gastrointestinal tract in growing
      pigs.
AB  - The objective of this study was to evaluate the impact of tylosin phosphate (TP)
      on energy and nutrient digestibility and flow through the gastrointestinal tract
      in growing pigs fed corn-soybean meal or corn-soybean meal-distillers dried
      grains with solubles (DDGS) based diets. Eighteen barrows (initial BW = 32.6 +/-
      1.2 kg) were surgically fitted with a T-cannula in the distal ileum and allotted
      to a Youden square design with 6 diets and 3 replicate periods. Treatments were
      arranged in a 2 * 2 factorial: TP (0 vs. 44 mg/kg) and DDGS (0 vs. 25%). Two N
      free dietary treatments (0 vs. 44 mg/kg TP) were also included for determining
      basal ileal endogenous AA losses (IAAend) and the effect of TP on basal IAAend.
      Replicate periods included 4 d of adaptation to treatments and 2 sampling
      periods. Fecal collection occurred on d 5 and 6 and ileal digesta collection
      occurred on d 7 and 8 for sampling period 1 whereas sampling period 2 included
      fecal collection on d 11 and 12 and ileal digesta collection on d 13 and 14.
      Apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD)
      were calculated for DM, energy, and NDF. The AID and standardized ileal
      digestibility (SID) of AA were calculated. Inclusion of DDGS reduced AID (68.0
      vs. 72.8%; P < 0.001) and ATTD (79.9 vs. 85.0%; P < 0.001) of energy. There were
      no effects of TP on energy digestibility. The DDGS inclusion increased the amount
      of GE (1.47 vs. 1.18 Mcal/kg DMI; P < 0.001) and NDF (94 vs. 60 g/kg DMI; P <
      0.001) remaining at the terminal ileum; however, hindgut disappearance of energy
      (0.55 vs. 0.53 Mcal/kg DMI) and NDF (13 vs. 15 g/kg DMI) was similar between the
      corn-soybean meal-DDGS and corn-soybean meal based diets. There were no effects
      of TP on basal IAAend; therefore, SID AA values were calculated using means of
      the 2 N-free diets. The SID of Lys (79.6 vs. 84.1%; P < 0.001) and all other
      indispensible AA, except Leu, was lower in the DDGS diets. Inclusion of TP did
      not influence SID of AA. In conclusion, under the conditions of this experiment,
      TP did not affect digestibility of AA or the digestibility and gastrointestinal
      tract flow of energy and the inclusion of DDGS did not affect the response to TP.

PMID- 24126275
TI  - Bacillus cereus var. Toyoi modulates the immune reaction and reduces the
      occurrence of diarrhea in piglets challenged with Salmonella Typhimurium DT104.
AB  - A feeding trial with sows and their piglets was performed with the probiotic feed
      additive Bacillus cereus var. Toyoi in two consecutive experimental periods. Sows
      (n = 8) were allocated into treatment (Bc) and control (CO) groups. Sows of Bc
      group (n = 4) were fed 3.14 * 10(5) cfu/g Bacillus cereus var. Toyoi with the
      diet from d 87 of pregnancy on. Their piglets received Bacillus cereus var. Toyoi
      supplemented feed (8.7 * 10(5) cfu/g) starting on d 14 of life and further on
      after weaning (6.5 * 10(5) cfu/g), whereas sows and piglets of the CO group
      remained untreated. One day after weaning, piglets from both groups (n = 24 each)
      were challenged orally with Salmonella Typhimurium DT104 (3 * 10(9) viable
      bacteria). Health status, shedding of B. cereus in the feces, and performance of
      the piglets were monitored. At 24 h, 72 h, 6 d, and 28 d postinfection (PI), six
      piglets from each group were euthanized and cell counts of Salmonellae were
      determined in the colon contents, mesenteric lymph nodes, and tonsils. Peripheral
      blood mononuclear cells and jejunal intraepithelial lymphocytes (IEL) were
      analyzed by flow cytometry. The incidence of scours was lower in the Bc group
      than in the CO group (P = 0.004). In addition, the fecal shedding of Salmonella
      was significantly lower in the Bc group at 25 d PI (P = 0.004). Shortly after
      infection, the gammadelta T cells were significantly less frequent in the blood
      of Bc piglets. For both CD8-positive gammadelta T cells (P = 0.033) and CD8
      negative gammadelta T cells (P = 0.028), significant differences were observed.
      Furthermore, 28 d PI piglets from the treated group showed lower numbers of
      gammadelta T cells in the jejunal epithelium (P = 0.036). To investigate the role
      of intestinal gammadelta T cells during the infection with S. Typhimurium, IEL
      were gained from six healthy 40-d-old piglets and infected in vitro with S.
      Typhimurium. CD8beta cells and gammadelta T cells were detected by flow cytometry
      and the infection rates of both populations in the cell suspensions were
      compared. The infection rate (IR) of gammadelta T cells was higher in all six
      cell suspensions than the IR of CD8beta expressing T cells (P = 0.002). In
      conclusion, B. cereus var. Toyoi supplementation of sows and their piglets had a
      positive impact on the health status of the piglets after a challenge with
      Salmonella, likely due to an altered immune response marked by reduced
      frequencies of CD8+ gammadelta T cells in the peripheral blood and the jejunal
      epithelium. 

PMID- 24126276
TI  - Dietary plant extracts improve immune responses and growth efficiency of pigs
      experimentally infected with porcine reproductive and respiratory syndrome virus.
AB  - A study was conducted to evaluate the effects of 3 different plant extracts on
      growth performance and immune responses of weaned pigs experimentally infected
      with porcine reproductive and respiratory syndrome virus (PRRSV). A total of 64
      weaned pigs (7.8 +/- 0.3 kg BW), free of PRRSV, were randomly allotted to 1 of 8
      treatments in a 2 * 4 factorial arrangement with a randomized complete block
      design. Pigs were blocked by initial BW. Sex and ancestry were equalized across
      treatments. The first factor was with or without PRRSV challenge (intranasal
      dose; 10(5) 50% tissue culture infective dose). The second factor was represented
      by 4 diets: a nursery basal diet (CON), 10 mg/kg capsicum oleoresin (CAP), garlic
      botanical (GAR), or turmeric oleoresin (TUR). Pigs were housed in disease
      containment chambers for 28 d [14 d before and after the inoculation (d 0)].
      Blood was collected on d 0, 7, and 14 to measure the total and differential white
      blood cells (WBC), and serum was collected to measure viral load by quantitative
      PCR, PRRSV antibody titer, tumor necrosis factor-alpha (TNF-alpha), IL-1beta, C
      reactive protein (CRP), and haptoglobin (Hp) by ELISA. In the unchallenged group,
      all piglets were PRRSV negative during the overall period postinoculation. All
      data were analyzed using PROC MIXED of SAS. The PRRSV challenge decreased (P <
      0.01) ADG, ADFI, and G:F from d 0 to 14. Feeding TUR improved G:F of the PRRSV
      infected pigs from d 0 to 14. The numbers of WBC and neutrophils were decreased
      (P < 0.05) by PRRSV on d 7 but increased (P < 0.05) by PRRSV on d 14, indicating
      the PRRSV-infected pigs undergo a stage of weak immune responses. Feeding GAR
      increased (P < 0.05) B cells and CD8+ T cells of PRRSV-infected pigs compared
      with the CON. Furthermore, the PRRSV challenge increased (P < 0.05) serum viral
      load, TNF-alpha, and IL-1beta on d 7 and serum viral load, CRP, and Hp on d 14,
      but feeding plant extracts to PRRSV-infected pigs reversed (P < 0.05) this
      increase. Infection with PRRSV increased (P < 0.05) rectal temperature of pigs on
      d 7, 9, and 11, but PRRSV-infected pigs fed plant extracts had lower rectal
      temperature (P < 0.05) than pigs fed the CON, indicating feeding plant extracts
      delayed the fever caused by PRRSV infection. In conclusion, results indicate that
      supplementation with plant extracts reduces the adverse effects of PRRSV by
      improving the immune responses of pigs, and the 3 plant extracts tested here show
      different effects. Supplementation with TUR improved feed efficiency of pigs
      challenged with PRRSV. 

PMID- 24126277
TI  - Molecular value predictions: associations with beef quality, carcass, production,
      behavior, and efficiency phenotypes in Brahman cattle.
AB  - Data from 2 previously published experiments, New South Wales (NSW; n = 161) and
      Western Australia (WA; n = 135), were used to test molecular value predictions
      (MVP), generated from commercially available gene markers, on economically
      important traits of Bos indicus (Brahman) cattle. Favorable tenderness MVP scores
      were associated with reduced shear force values of strip loin (LM) steaks aged 7
      d from Achilles-hung carcasses (P <= 0.06), as well as steaks aged 1 (P <= 0.08)
      or 7 d (P <= 0.07) from carcasses hung from the pelvis (tenderstretch). Favorable
      tenderness MVP scores were also associated with improved consumer tenderness
      ratings for strip loin steaks aged 7 d and either Achilles hung (P <= 0.006) or
      tenderstretched (P <= 0.07). Similar results were observed in NSW for rump (top
      butt; gluteus medius) steaks, with favorable tenderness MVP scores associated
      with more tender (P = 0.006) and acceptable (P = 0.008) beef. Favorable marbling
      MVP scores were associated with improved (P <= 0.021) marbling scores and
      intramuscular fat (IMF) content in the NSW experiment, despite low variation in
      marbling in the Brahman cattle. For the WA experiment, however, there were no (P
      >= 0.71) relationships between marbling MVP and marbling scores or IMF content.
      Although residual (net) feed intake (RFI) was not associated (P = 0.63) with the
      RFI (feed efficiency) MVP, the RFI MVP was adversely associated with LM
      tenderness and acceptability of 7-d-aged Achilles-hung carcasses in NSW (P <=
      0.031) and WA (P <= 0.037). Some other relationships and trends were noted
      between the MVP and the other traits, but few reached statistical significance,
      and none were evident in both experiments. Results from this study provide
      evidence to support the use of the tenderness MVP. The value of the marbling MVP,
      which was associated with marbling in only 1 herd, warrants further evaluation;
      however, there appears to be no evidence to support use of the RFI MVP in Brahman
      cattle. 

PMID- 24126278
TI  - Moisture content in broiler excreta is influenced by excreta nutrient contents.
AB  - High litter moisture content, often referred to as wet litter, is a major problem
      in poultry production. Wet litter is often related to poor management, diseases,
      and digestive problems. In this experiment, the objective was to study the
      relationship between nutrient content and the moisture content of the excreta of
      broilers. A dataset containing 351 observations was built and contained the
      nutrient contents data including moisture content of excreta samples collected in
      8 different broiler feeding trials. A biological based model approach was used to
      create a model with 10 and another one with 14 variables that may explain the
      excreta moisture level response. Subsequently, these models were compared with a
      statistical model that was built automatically and adjusted only if this improved
      the biological model. The R(2) of the 10 variable model was 0.54, in which Zn
      content and the interaction of NDF * K and Ca * P content were negatively
      associated with excreta moisture. Sodium, P, and Ca content and the interaction
      between content of NDF * Na were positively associated with excreta moisture. The
      R(2) of the 14 variable model was 0.58, in which Zn and K content and the
      interaction of NDF * protein and Ca * P content were negatively associated with
      excreta moisture, and Na, protein, P, and Ca content and the interactions in
      contents of NDF * Na, NDF * Zn, and K * Cu were positively associated with
      excreta moisture content. In conclusion, the models confirmed the effect of Na,
      protein, P, and Ca on excreta moisture content. Furthermore, hitherto unknown
      nutrient interactions that contribute to excreta moisture level were identified.
      As excreta levels of most nutrients can be manipulated by adjusting dietary
      nutrient levels, dietary formulation can be adjusted with the findings of this
      analysis to change levels of excreted nutrients and, consequently, also moisture
      output. 

PMID- 24126279
TI  - Quantum-criticality-induced strong Kerr nonlinearities in optomechanical systems.
AB  - We investigate a hybrid electro-optomechanical system that allows us to realize
      controllable strong Kerr nonlinearities even in the weak-coupling regime. We show
      that when the controllable electromechanical subsystem is close to its quantum
      critical point, strong photon-photon interactions can be generated by adjusting
      the intensity (or frequency) of the microwave driving field. Nonlinear optical
      phenomena, such as the appearance of the photon blockade and the generation of
      nonclassical states (e.g., Schrodinger cat states), are demonstrated in the weak
      coupling regime, making the observation of strong Kerr nonlinearities feasible
      with currently available optomechanical technology. 

PMID- 24126280
TI  - Involvement of spinal release of alpha-neo-endorphin on the antinociceptive
      effect of TAPA.
AB  - The antinociceptive effect of i.t.-administered Tyr-d-Arg-Phe-beta-Ala (TAPA), an
      N-terminal tetrapeptide analog of dermorphin, was characterized in ddY mice. In
      the mouse tail-flick test, TAPA administered i.t. produced a potent
      antinociception. The antinociception induced by TAPA was significantly attenuated
      by i.t. pretreatment with the kappa-opioid receptor antagonist nor
      binaltorphimine, as well as by the MU-opioid receptor antagonist beta
      funaltrexamine and the MU1-opioid receptor antagonist naloxonazine. TAPA-induced
      antinociception was also significantly suppressed by co-administration of the MU1
      opioid receptor antagonist Tyr-d-Pro-Phe-Phe-NH2 (d-Pro(2)-endomorphin-2) but not
      by co-administration of the MU2-opioid receptor antagonists Tyr-d-Pro-Trp-Phe-NH2
      (d-Pro(2)-endomorphin-1) and Tyr-d-Pro-Trp-Gly-NH2 (d-Pro(2)-Tyr-W-MIF-1). In
      CXBK mice whose MU1-opioid receptors were naturally reduced, the antinociceptive
      effect of TAPA was markedly suppressed compared to the parental strain C57BL/6ByJ
      mice. Moreover, the antinociception induced by TAPA was significantly attenuated
      by i.t. pretreatment with antiserum against the endogenous kappa-opioid peptide
      alpha-neo-endorphin but not antisera against other endogenous opioid peptides. In
      prodynorphin-deficient mice, the antinociceptive effect of TAPA was significantly
      reduced compared to wild-type mice. These results suggest that the spinal
      antinociception induced by TAPA is mediated in part through the release of alpha
      neo-endorphin in the spinal cord via activation of spinal MU1-opioid receptors. 

PMID- 24126282
TI  - The median raphe nucleus participates in the depressive-like behavior induced by
      MCH: differences with the dorsal raphe nucleus.
AB  - An emerging body of evidence involves the hypothalamic neuropeptide melanin
      concentrating hormone (MCH) in the regulation of emotional states. We have
      reported a pro-depressive effect induced by MCH after its microinjection into the
      dorsal raphe nucleus (DR) evaluated in the forced swimming test (FST) in rats.
      Here we extended this study to the median raphe nucleus (MnR). Firstly, the
      presence of MCH-containing fibers in the rat MnR was analyzed by means of
      immunohistochemistry. Secondly, the behavioral effect induced by the
      microinjection of MCH into the MnR was assessed using the FST. Morphological
      results showed a large density of MCHergic fibers within the MnR. Behavioral
      results indicated that 100 ng of MCH (but not 50 ng) significantly increased the
      immobility time and decreased the swimming time, demonstrating a depressive-like
      effect. In contrast, climbing behavior was not significantly affected. Present
      findings revealed that the MnR neurons participate in the MCHergic control of
      affective-related behavioral responses. However, the behavioral patterns induced
      by MCH in the MnR and DR were different. This could be explained by anatomical
      and physiological differences between both nuclei.

PMID- 24126281
TI  - Endogenous opiates and behavior: 2012.
AB  - This paper is the thirty-fifth consecutive installment of the annual review of
      research concerning the endogenous opioid system. It summarizes papers published
      during 2012 that studied the behavioral effects of molecular, pharmacological and
      genetic manipulation of opioid peptides, opioid receptors, opioid agonists and
      opioid antagonists. The particular topics that continue to be covered include the
      molecular-biochemical effects and neurochemical localization studies of
      endogenous opioids and their receptors related to behavior (Section 2), and the
      roles of these opioid peptides and receptors in pain and analgesia (Section 3);
      stress and social status (Section 4); tolerance and dependence (Section 5);
      learning and memory (Section 6); eating and drinking (Section 7); alcohol and
      drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development
      and endocrinology (Section 9); mental illness and mood (Section 10); seizures and
      neurologic disorders (Section 11); electrical-related activity and
      neurophysiology (Section 12); general activity and locomotion (Section 13);
      gastrointestinal, renal and hepatic functions (Section 14); cardiovascular
      responses (Section 15); respiration and thermoregulation (Section 16); and
      immunological responses (Section 17). 

PMID- 24126283
TI  - Ultrastructural and immunohistopathological evaluation of intravesical ureters
      via electron and light microscopy in children with vesicoureteral reflux.
AB  - PURPOSE: We used immunohistochemical methods and transmission electron microscopy
      to investigate the cytokine profiles and ultrastructural changes in the
      ureterovesical junction of children with primary vesicoureteral reflux. MATERIALS
      AND METHODS: A total of 39 distal intravesical ureters were obtained from 23
      children who underwent ureteroneocystostomy for primary vesicoureteral reflux.
      Ureteral wall smooth muscle organization and transforming growth factor-beta1,
      vascular endothelial growth factor and CD34 were evaluated immunohistochemically
      and compared to controls, which consisted of 10 age matched autopsy specimens.
      Ultrastructural evaluations and morphological descriptions were performed
      semiquantitatively and compared to the published data. RESULTS: Of the patients 6
      (26%) were male and 17 (74%) were female, and mean +/- SD age was 73.2 +/- 34.3
      months (range 12 to 168). There was no correlation between reflux grade and age
      (p = 0.39). Smooth muscle disorganization score differed significantly between
      patients with intravesical ureters and controls (p = 0.01). Transforming growth
      factor-beta1 levels were significantly higher (p = 0.001) and vascular
      endothelial growth factor levels and microvessel densities were significantly
      lower in the patients with reflux compared to controls (both p <0.001). Vascular
      endothelial growth factor, CD34 and transforming growth factor-beta1 levels did
      not correlate with reflux grades (p = 0.84, p = 0.76 and p = 0.10, respectively).
      Urothelium, lamina propria and tunica adventitia appeared normal in the specimens
      for all grades of vesicoureteral reflux using transmission electron microscopy.
      Damage was observed in the muscular layers of the ureterovesical junction,
      especially in patients with grade IV or V reflux. CONCLUSIONS: Primary refluxing
      ureters exhibit immunohistopathological abnormalities compared to normal ureters
      irrespective of reflux grade, and ultrastructural changes are especially severe
      in cases of high grade reflux. These abnormalities can hinder the normal ureteral
      valve mechanism, and may lead to reflux due to smooth muscle dysfunction and
      microvascular alterations.

PMID- 24126284
TI  - Reminiscences of research on the chemistry and biology of natural sterols in
      insects, plants and humans.
AB  - Natural sterols often occur as a heterogeneous mixture of homologs, which had
      disturbed the progress of steroid research. Development and application of GC
      methodology overcame this difficulty and enabled us to obtain detailed sterol
      profiles. Together, fine synthesis of stereo-defined isomers and homologs of
      steroids having oxygenated side chains allowed us to compare them with natural
      samples as well as to investigate structure-activity relationship. Advance of
      HPLC technology also facilitated the determination of the stereochemical
      structure of naturally occurring steroidal compounds, which were obtained only in
      minute amounts. This review highlights three topics out of our steroid research
      that have been performed mainly at Tokyo Institute of Technology around 1970
      1990. These are sterol metabolism in insects focusing on the mechanism of the
      conversion of plant sterols to cholesterol and ecdysone biosynthesis, the
      synthesis and biochemical research of active forms of vitamin D3 derivatives, and
      the synthesis and microanalysis of plant hormone brassinosteroids.

PMID- 24126285
TI  - The biological significance of omega-oxidation of fatty acids.
AB  - The author focuses on the biological significance of omega-oxidation of fatty
      acids. Early studies revealed that there is a subsidiary pathway for beta
      oxidation of fatty acids when beta-oxidation is blocked. Many studies
      demonstrated that the omega-oxidation serves to provide succinyl-CoA for the
      citric acid cycle and for gluconeogenesis under conditions of starvation and
      diabetes. Acylglucosylceramides which are composed of linoleic acid, long chain
      omega-hydroxy fatty acids, eicosasphingenine (or trihydroxyeicosasphingenine) and
      glucose, are responsible for normal epidermal permeability function in the skin.
      It is observed that omega- and (omega-1)-oxidation of fatty acids are related to
      energy metabolism in some laboratory animals such as musk shrews and Mongolian
      gerbils. Studies confirmed that omega- and (omega-1)-oxidation of fatty acids
      play crucial roles in the production of insect pheromones of honeybees and in the
      formation of biopolyesters of higher plants. In addition, the biological
      significance of omega-oxidation of prostaglandins and leukotrienes is described.

PMID- 24126286
TI  - A large hydrothermal reservoir beneath Taal Volcano (Philippines) revealed by
      magnetotelluric observations and its implications to the volcanic activity.
AB  - Taal Volcano is one of the most active volcanoes in the Philippines. The
      magnetotelluric 3D forward analyses indicate the existence of a large high
      resistivity anomaly (~100 Omega.m) with a volume of at least 3 km*3 km*3 km,
      which is capped by a conductive layer (~10 Omega.m), beneath the Main Crater.
      This high resistivity anomaly is hypothesized to be a large hydrothermal
      reservoir, consisting of the aggregate of interconnected cracks in rigid and
      dense host rocks, which are filled with hydrothermal fluids coming from a magma
      batch below the reservoir. The hydrothermal fluids are considered partly in gas
      phase and liquid phase. The presence of such a large hydrothermal reservoir and
      the stagnant magma below may have influences on the volcano's activity. Two
      possibilities are presented. First, the 30 January 1911 explosion event was a
      magmatic hydrothermal eruption rather than a base-surge associated with a phreato
      magmatic eruption. Second, the earlier proposed four eruption series may be
      better interpreted by two cycles, each consisting of series of summit and flank
      eruptions.

PMID- 24126287
TI  - National survey of thrombolytic therapy for acute ischemic stroke in Taiwan 2003
      2010.
AB  - Data on thrombolytic therapy at the national level is scarce in Asia.
      Understanding current practice pattern is important for a policy maker in
      decision making. This cross-sectional study analyzed the utilization pattern of
      thrombolytic therapy for acute ischemic stroke (AIS) in Taiwan from 2003 through
      2010 and identified factors associated with post-therapy intracerebral hemorrhage
      (ICH) and mortality. From the Taiwan National Health Insurance Research Database,
      we retrieved inpatient claims for patients with AIS. The frequency of
      thrombolytic therapy in AIS admissions and its association with the
      characteristics of patients, physicians, and hospitals were analyzed. Factors
      predicting ICH and in-hospital mortality were also analyzed using multiple
      logistic regressions. Of 394,988 patients with AIS, 2385 (.60%) had received
      thrombolytic therapy. The utilization rate increased from .03% in 2003 to 1.51%
      in 2010. Thrombolytic therapy was adopted earlier in a belt of high-frequency
      counties across rural midwestern Taiwan, twice the rate in the Taipei and
      Kaohsiung cities. The neurology specialty and hospital's service volume were the
      most dominant factors related to higher utilization, in addition to weekend
      admission and the patient's age and comorbidities. ICH and in-hospital mortality
      rates were 3.48% and 7.71%, respectively. Patients given thrombolytic therapy in
      hospitals with thrombolysis cases more than the 5.5/year had a lower risk of ICH
      (odds ratio: .53; 95% confidence interval: .31-.88). Compared with most developed
      countries, there is indeed much unmet need for stroke thrombolysis in Taiwan.
      Effective mechanism should be implemented to increase the thrombolysis rate
      safely and improve outcome for patients with AIS. 

PMID- 24126288
TI  - MRI-guided sonothrombolysis of rabbit carotid artery.
AB  - The potential of magnetic resonance imaging-guided focused ultrasound (MRgFUS)
      combined with the thrombolytic drug recombinant tissue plasminogen activator (rt
      PA) to dissolve clots in the carotid of a New Zealand rabbit in vivo is
      evaluated. A spherically focused transducer of 5-cm diameter, focusing at 10 cm
      and operating at 1 MHz, was used. A pulsed ultrasound protocol was used that
      maintains a tissue temperature increase of less than 1  degrees C in the clot
      (called safe temperature). MRgFUS has the potentials to dissolve clots that are
      injected in the carotid of rabbits in vivo. It was found that the time needed for
      opening the carotid artery using ultrasound and rt-PA was decreased compared with
      just using rt-PA. The time needed for opening the artery decreases with
      increasing acoustic intensity. With an intensity of 20 W/cm2 (spatial average
      temporal average), which is not causing artery heating, the time needed to
      completely open the artery was 70 minutes. The proposed protocol was monitored
      using magnetic resonance angiography every 1 minute.

PMID- 24126289
TI  - Prevalence of Fabry disease in stroke patients--a systematic review and meta
      analysis.
AB  - BACKGROUND: Fabry disease is an uncommon but treatable cause of stroke. Enzyme
      replacement therapy helps improve neurologic symptoms. We conducted a systematic
      review and meta-analysis to evaluate the prevalence of Fabry disease in stroke
      patients. METHODS: We searched MEDLINE and EMBASE databases for relevant articles
      published in English up to February 2013. Studies that reported incidence or
      prevalence of Fabry disease in stroke patients were included. Two reviewers
      independently assessed studies to determine eligibility, validity, and quality.
      Meta-analysis was performed to calculate the prevalence of Fabry disease by
      etiology and gender. RESULTS: Nine studies (n = 8302 patients) met the inclusion
      criteria. Eight studies (n = 8148) examined the prevalence of Fabry disease in
      young stroke patients. Overall qualities of included studies were moderate to
      high. The prevalence of Fabry disease ranged from .4% to 2.6% on strokes of any
      etiologies. In cryptogenic stroke, the prevalence ranged from .6% to 11.1%, 4.5%
      in men (95% confidence interval [CI] = 3.2%-6.3%) and 3.4% in women (95% CI =
      1.0%-10.7%). The prevalence of Fabry disease in patients with all etiologies was
      similar in men (.9% [95% CI = .3%-2.3%]) and (1.4% [95% CI = .7%-2.7%]) in women.
      CONCLUSIONS: Fabry disease may explain approximately 1% of all strokes in the
      young, including 3%-5% of cryptogenic strokes. The confirmation of Fabry disease
      may be challenging as there are different criteria for men and women. Early
      recognition of Fabry disease may help initiate the appropriate treatment to
      decrease the risk of subsequent complications.

PMID- 24126293
TI  - Dithienopyrrole-based oligothiophenes for solution-processed organic solar cells.
AB  - Isomeric dicyanovinylene-terminated oligothiophenes 1 and 2 comprising a central
      dithienopyrrole (DTP) unit have been developed for solution-processed small
      molecule organic solar cells (SMOSCs) giving the highest power conversion
      efficiency of 4.8% for DTP-based oligomeric materials.

PMID- 24126290
TI  - Comparison of aspirin response measured by urinary 11-dehydrothromboxane B2 and
      VerifyNow aspirin assay in patients with ischemic stroke.
AB  - BACKGROUND: We looked for the prevalence of aspirin nonresponders, compared the
      results of 2 tests assessing aspirin responses-measurement of urinary 11
      dehydrothromboxane B2 (dTXB2) and VerifyNow Aspirin assay-in patients with
      ischemic stroke, and examined the relationship of aspirin nonresponse and the
      outcomes of the patients. METHODS: One hundred one patients with ischemic stroke
      were prospectively included. Aspirin response was assessed by urinary dTXB2
      measurement and VerifyNow Aspirin assay. The Spearman correlation coefficients
      and kappa statistics were calculated to assess correlation and agreement between
      the 2 tests. The measured outcome was the occurrence of cardiovascular events and
      death. RESULTS: Prevalence of aspirin nonresponders was 40% and 6%, if they were
      measured by urinary dTXB2 and VerifyNow Aspirin assay, respectively. Poor
      correlation in the results between the 2 tests was found (r = .135, P = .190).
      The degree of agreement between the 2 tests in relation to resistance status was
      weak (kappa = .032, P = .590). With a mean follow-up time of 17 months, the
      outcomes occurred significantly higher in aspirin nonresponders who were
      diagnosed by urinary dTXB2 measurement as compared with patients with aspirin
      response (18% versus 2%, odds ratio 8.8, 95% confidence interval 1.18-65.4, P =
      .037). CONCLUSIONS: Our research confirmed poor correlation and lack of agreement
      between the 2 tests. Only aspirin nonresponders who were diagnosed by dTXB2
      measurement were related to having cardiovascular events and death. Further
      research is still needed to identify the best method of diagnosis of aspirin
      nonresponders.

PMID- 24126296
TI  - In situ atomic-scale visualization of oxide islanding during oxidation of Cu
      surfaces.
AB  - Oxidation of Cu occurs via Cu2O islanding on an oxide wetting layer at a critical
      thickness of two atomic layers. The transition from 2D wetting-layer growth to 3D
      oxide islanding is driven energetically arising from the Cu-Cu2O interfacial
      interaction. 

PMID- 24126297
TI  - Taking Charge: Front-Line Nurse Leadership Development.

PMID- 24126295
TI  - The CHANGE study: a healthy-lifestyles intervention to improve rural children's
      diet quality.
AB  - BACKGROUND: Despite the high rates of overweight and obesity among rural
      children, there have been limited interventions reported to improve the diet
      quality of rural, low-income children in the United States. OBJECTIVE: Our aim
      was to evaluate students' diet quality at baseline and after implementing the
      CHANGE (Creating Healthy, Active and Nurturing Growing-Up Environments) study, a
      2-year (2007-2009) randomized, controlled, community- and school-based
      intervention to prevent unhealthy weight gain among rural school-aged children.
      DESIGN: We used a school and community-based group randomized, controlled design.
      PARTICIPANTS/SETTING: Data were collected in eight rural communities in
      California, Kentucky, Mississippi, and South Carolina (one elementary school per
      community). Children in grades 1 to 6 participated in the study (n=432; mean
      age=8.65 years +/- 1.6 years). Students' diets were assessed at baseline (spring
      or early fall 2008) and post intervention (spring 2009) using the Block Food
      Screener for ages 2 to 17 years. STATISTICAL ANALYSES: Mixed-model analysis of
      variance was used to examine the effect of the CHANGE study intervention on
      students' diets. Results were adjusted for corresponding baseline dietary values,
      sex, age, grade, race/ethnicity, and state, with school included as a random
      effect nested within condition. RESULTS: At the end of 1 year, students enrolled
      in the CHANGE study intervention schools consumed significantly more vegetables
      (0.08 cups/1,000 kcal/day; P=0.03) and combined fruits and vegetables (0.22
      cups/1,000 kcal/day; P<0.05) compared with students in control schools. Students
      in the intervention schools also showed a reduction in the average daily dietary
      glycemic index (GI=-1.22; P<0.05) and a trend toward more fruit consumption (0.15
      cups/1,000 kcal/day; P=0.07). There were no significant differences in students'
      consumption of whole grains, legumes, dairy, potatoes/potato products, saturated
      fat, added sugars, or dietary fiber consumption. CONCLUSIONS: The CHANGE study
      enhanced some aspects of rural students' dietary intake. Implementing similar
      interventions in rural America can be promising to support vegetable consumption.

PMID- 24126298
TI  - Detection of the deletion of the STS gene and flanking sequences using polymerase
      chain reaction in a Chinese pedigree: the first case report of X-linked
      ichthyosis associated with testicular microlithiasis.

PMID- 24126299
TI  - Knowledge of pelvic floor disorders in a population of community-dwelling women.
AB  - OBJECTIVE: The objective of the study was to investigate baseline knowledge and
      demographic factors associated with a lack of knowledge about urinary
      incontinence (UI) and pelvic organ prolapse (POP). STUDY DESIGN: This study was a
      community-based, cross-sectional survey of 431 racially and socioeconomically
      diverse women aged 19-98 years. The Prolapse and Incontinence Knowledge
      Questionnaire was used to assess participants' knowledge. Primary endpoints were
      the total number of correct responses on the UI and POP scales, respectively.
      Percentages of individuals answering each item or group of items correctly were
      explored as secondary outcomes. RESULTS: All women lacked knowledge proficiency
      about UI and POP, although knowledge about UI was slightly greater than knowledge
      about POP. Overall, 71.2% of subjects lacked UI proficiency (<80% correct),
      whereas 48.1% lacked proficiency in POP knowledge (<50% correct). Black women
      demonstrated significantly less knowledge about UI and POP than white women, both
      before and after adjustment for age, education, and household income. When
      combined into 1 group, Asian, Hispanic, and other women also showed significantly
      less UI and POP knowledge than white women. Most women who reported symptoms of
      UI had not received treatment for their problems. CONCLUSION: There is a global
      lack of knowledge about UI and POP among community-dwelling women, with more
      pronounced knowledge gaps among nonwhite women. UI and POP are chronic medical
      conditions that should be included in routine screening questions for well-woman
      care. Further studies are needed to explore how best to educate and improve
      women's awareness of these prevalent pelvic floor disorders.

PMID- 24126300
TI  - Evaluation and management of complications from synthetic mesh after pelvic
      reconstructive surgery: a multicenter study.
AB  - OBJECTIVE: The purpose of this study was to describe the evaluation and
      management of synthetic mesh-related complications after surgery for stress
      urinary incontinence (SUI) and/or pelvic organ prolapse (POP). STUDY DESIGN: We
      conducted a multicenter, retrospective analysis of women who attended 4 US
      tertiary referral centers for evaluation of mesh-related complications after
      surgery for SUI and/or POP from January 2006 to December 2010. Demographic,
      clinical, and surgical data were abstracted from the medical record, and
      complications were classified according to the Expanded Accordion Severity
      Classification. RESULTS: Three hundred forty-seven patients sought management of
      synthetic mesh-related complications over the study period. Index surgeries were
      performed for the following indications: SUI (sling only), 49.9%; POP
      (transvaginal mesh [TVM] or sacrocolpopexy only), 25.6%; and SUI + POP (sling +
      TVM or sacrocolpopexy), 24.2%. Median time to evaluation was 5.8 months (range, 0
      65.2). Thirty percent of the patients had dyspareunia; 42.7% of the patients had
      mesh erosion; and 34.6% of the patients had pelvic pain. Seventy-seven percent of
      the patients had a grade 3 or 4 (severe) complication. Patients with TVM or
      sacrocolpopexy were more likely to have mesh erosion and vaginal symptoms
      compared with sling only. The median number of treatments for mesh complications
      was 2 (range, 1-9); 60% of the women required >=2 interventions. Initial
      treatment intervention was surgical for 49% of subjects. Of those treatments that
      initially were managed nonsurgically, 59.3% went on to surgical intervention.
      CONCLUSION: Most of the women who seek management of synthetic mesh complication
      after POP or SUI surgery have severe complications that require surgical
      intervention; a significant proportion require >1 surgical procedure. The pattern
      of complaints differs by index procedure.

PMID- 24126319
TI  - Gelatin-carrageenan hydrogels: role of pore size distribution on drug delivery
      process.
AB  - Naturally occurring biomaterials, such as gelatin and carrageenan are known to
      act as good drug delivering agents. The physical properties of these hydrogels
      are derived from their pore network. The effect of pore size distribution of
      hydrogel on the drug delivery process has been studied in this work. Gelatin
      carrageenan hydrogel has been characterized using DSC, TGA and SEM.
      Thermoporometry technique has been used since it offers the measurement to be
      carried out in native state without drying the sample. Release of quercetin
      (Q,3,5,7,3',4'-pentahydroxyflavone), a member of the flavonoids family, which
      exerts many beneficial health effects has been studied using gelatin-carrageenan
      hydrogel. The addition of gelatin to carrageenan is found to improve the thermal
      stability of the gelatin-carrageenan fibers in the composite hydrogels. The in
      vitro drug release studies have shown that an increase in porosity results in the
      improved drug release. The tuning of pore size distribution for drug delivery
      applications using thermoporometry is feasible. 

PMID- 24126320
TI  - Tailoring the hydrophobicity of graphene for its use as nanopores for DNA
      translocation.
AB  - Graphene nanopores are potential successors to biological and silicon-based
      nanopores. For sensing applications, it is however crucial to understand and
      block the strong nonspecific hydrophobic interactions between DNA and graphene.
      Here we demonstrate a novel scheme to prevent DNA-graphene interactions, based on
      a tailored self-assembled monolayer. For bare graphene, we encounter a paradox:
      whereas contaminated graphene nanopores facilitated DNA translocation well, clean
      crystalline graphene pores very quickly exhibit clogging of the pore. We
      attribute this to strong interactions between DNA nucleotides and graphene,
      yielding sticking and irreversible pore closure. We develop a general strategy to
      noncovalently tailor the hydrophobic surface of graphene by designing a dedicated
      self-assembled monolayer of pyrene ethylene glycol, which renders the surface
      hydrophilic. We demonstrate that this prevents DNA to adsorb on graphene and show
      that single-stranded DNA can now be detected in graphene nanopores with excellent
      nanopore durability and reproducibility. 

PMID- 24126321
TI  - [In vitro study over statins effects on cellular growth curves and its
      reversibility with mevalonate].
AB  - HMG-CoA-Reductase inhibitors, also known as statins, are currently the most
      powerful cholesterol-lowering drugs available on the market. Clinical trials and
      experimental evidence suggest that statins have heavy anti-atherosclerotic
      effects. These are in part consequence of lipid lowering but also result from
      pleiotropic actions of the drugs. These so-called pleiotropic properties affect
      various aspects of cell function, inflammation, coagulation, and vasomotor
      activity. These effects are mediated either indirectly through LDL-c reduction or
      via a direct effect on cellular functions. Although many of the pleiotropic
      properties of statins may be a class effect, some may be unique to certain agents
      and account for differences in their pharmacological activity. So, although
      statins typically have similar effects on LDL-c levels, differences in chemical
      structure and pharmacokinetic profile can lead to variations in pleiotropic
      effects. In this paper we analize the in vitro effects of different statins over
      different cell lines from cells implicated in atherosclerotic process:
      endothelial cells, fibroblasts, and vascular muscular cells. In relation with our
      results we can proof that the effects of different dosis of different statins
      provides singular effects over growth curves of different cellular lines, a
      despite of a class-dependent effects. So, pleiotropic effects and its
      reversibility with mevalonate are different according with the molecule and the
      dosis. 

PMID- 24126322
TI  - Partial aortic root remodeling in case of ascending aortic aneurysms.
AB  - OBJECTIVE: In degenerative ascending aortic aneurysms (AAAs), the pathological
      process may extend into the aortic root, causing aortic regurgitation (AR). As
      often one or two sinuses are involved, ascending aorta replacement should be
      associated with selected sinus replacement. METHODS: Thirty patients (21 men and
      9 women; mean +/- SD age, 70.0 +/- 10.4) were operated on for ascending aorta and
      selected sinus replacement. All patients had degenerative AAA with sinotubular
      junction and partial root dilatation: one or two sinuses of Valsalva were
      involved. Mild to moderate-severe AR was present in all patients. The mean +/- SD
      logistic EuroSCORE 1 was 15.4 +/- 12.5. Twenty patients had ascending aorta
      replacement associated with noncoronary sinus replacement; 8 patients, associated
      with both right and noncoronary sinuses; 1 patient, associated with both left and
      noncoronary sinuses; and 1 patient, associated with left coronary sinus alone.
      RESULTS: There were no hospital or late deaths. No thromboembolic event or
      bleeding complications were reported. Postoperative echocardiography did not show
      significant AR, and computed tomographic scanning revealed a normal positioning
      of the vascular graft in the ascending aorta. CONCLUSIONS: Remodeling of the
      sinotubular junction with selected sinus replacement in degenerative AAA is a
      valuable approach for aortic root remodeling, leading to a significant reduction
      of AR when the aortic leaflets are normal.

PMID- 24126323
TI  - Tumors metastatic to the heart.

PMID- 24126324
TI  - ECG response: October 15, 2013.

PMID- 24126325
TI  - Retinal and choroidal vascular occlusion after fat injection into the temple
      area.

PMID- 24126326
TI  - Shifting calcium plaque in progressive aortic dissection.

PMID- 24126328
TI  - Letter by Hyder and Barbara regarding article, "perioperative dexmedetomidine
      improves outcomes of cardiac surgery".

PMID- 24126329
TI  - Letter from Tripathi et al regarding article, "perioperative dexmedetomidine
      improves outcomes of cardiac surgery".

PMID- 24126330
TI  - Letter by Xue et al regarding article, "perioperative dexmedetomidine improves
      outcomes of cardiac surgery".

PMID- 24126331
TI  - Response to letters regarding article, "perioperative dexmedetomidine improves
      outcomes of cardiac surgery".

PMID- 24126333
TI  - Minimizing complications with the use of acellular dermal matrix for immediate
      implant-based breast reconstruction.
AB  - BACKGROUND: Acellular dermal matrix (ADM) use in implant-based breast
      reconstruction has been associated with higher rates of postoperative seroma and
      infection. This follow-up study was performed to determine whether specific
      modifications in technique are associated with a reduction in the rate of
      complications. METHODS: The authors performed a retrospective analysis of
      immediate ADM-assisted implant-based breast reconstructions performed by the lead
      author (Y.C.) during an 18-month period after instituting specific modifications
      to prevent seroma. These included draining both the submastectomy and sub-ADM
      planes, lowering the threshold for drain removal, and addition of postoperative
      soft compression dressings and surgical bras. A total of 179 implant-based
      reconstructions were evaluated for rates of complications, including infection,
      hematoma, seroma, and skin flap necrosis. These were compared to results of a
      series of 150 similar procedures performed by the lead author before institution
      of the procedural modifications described. RESULTS: Seroma rate decreased from
      18.6% to 4.7% (P = 0.0022), and major infection rate decreased from 7% to 1.9%
      (0.0250). CONCLUSIONS: Although implant-based breast reconstruction using ADM has
      been associated with increased seroma and possible infection rates, the use of
      specific clinical practices designed to prevent seroma has minimized our rate of
      these postoperative complications.

PMID- 24126334
TI  - Trapezial osteotomy for the treatment of trapezial dysplasia.
AB  - Dysplastic trapezium is a condition that is characterized by an exaggerated slant
      (slope) of the distal articular surface of the trapezium in relation to the axis
      of the second metacarpal. Usually, it becomes evident in the late teens and early
      20s with proximolateral subluxation of the base of the first metacarpal and is
      associated with pain at the base of the thumb. It is more common in the dominant
      hand of women, but can affect both hands and either sex. The condition can be
      progressively painful and incapacitating, and those patients will require early
      support with medical treatment. Surgical management is indicated in persistent
      cases. In this study, we aimed at correcting theabnormal trapezial tilt in
      nonarthritic trapeziometacarpal joints by a dorsoradial open wedge osteotomy and
      bone graft, restoring the normal biomechanics around the joint, abolishing the
      abnormal loads sustained by the ligaments, and aiming to prevent the development
      of arthritic changes. 

PMID- 24126335
TI  - Treatment of posttraumatic radial club hand with distraction lengthening.
AB  - The clinical and radiological results of distraction lengthening in cases with
      posttraumatic radial club hand were evaluated. Five patients (3 men and 2 women,
      with average age of 21 years) with traumatic radial shortening (3 patients had
      nonunited fracture of distal end radius with bone loss and 2 patients had short
      radius after malunited fracture of radius or growth arrest of distal radial
      epiphysis, the average shortening was 4.2 cm) were treated with distraction
      lengthening using Ilizarov fixator and hybrid fixation technique. Patients were
      evaluated clinically for hand function and appearance, and radiologically for
      union. The average follow-up was 25 months. The preplanned length was achieved in
      all cases with good union and no bone graft was needed, clinically there was much
      improvement in hand function (the range of motion of the wrist increased and the
      power of hand grip increased) and appearance. Pin tract infection occurred in 3
      cases, broken pin in 1 case, and stiff wrist in 1 case. These complications were
      treated and did not affect the final results. Acquired radial club hand is
      difficult to treat. Treatment with distraction lengthening is a good option with
      excellent results and mild complications that did not affect the overall results.

PMID- 24126336
TI  - Recycling of extracorporeally irradiated autograft for malignant bone tumors:
      long-term follow-up.
AB  - This study was conducted to evaluate the long-term oncological and functional
      outcomes. Forty-two patients (29 men and 13 women) with primary malignant bone
      tumors were included in this study. The procedure consisted of wide en bloc
      resection, clearing the extraosseous soft tissue and medullary content,
      extracorporeal irradiation with a single dose of 50 Gy using linear accelerator,
      and reimplantation using suitable fixation devices. The mean survivor follow-up
      was 54 months (24-174 months). There were 32 (76.2%) patients continuously
      disease free, 7 (16.7%) died of disease, and 3 (7.1%) alive with disease. Local
      recurrence was encountered in 4 (9.5%) patients. Nonunion occurred at 3 (6.4%)
      osteotomy sites. Deep infection developed in 4 (9.5%) cases. There were 13
      patients rated excellent, 17 good, 10 fair, and 2 failures according to the
      Mankin scoring system. The mean ratings of the Musculoskeletal Tumor Society
      score and the Toronto Extremity Salvage Score were 77 and 81, respectively. The
      long-term oncological and functional results are encouraging and suggest that
      extracorporeal irradiation and reimplantation can be a long-lasting biological
      reconstructive technique in properly selected patients. 

PMID- 24126337
TI  - Repair of thumb metacarpophalangeal joint ulnar collateral ligament injuries with
      microanchors.
AB  - INTRODUCTION: Ulnar collateral ligament (UCL) injuries of the metacarpophalangeal
      (MCP) joint of the thumb are common. Complete rupture can be a debilitating
      injury, resulting in decreased grip and pinch strength. PURPOSE: The present
      study evaluated prospectively the functional results of 27 patients who had open
      repair of the UCL of the thumb using microanchors either acutely or delayed (up
      to 9 weeks postinjury). METHODS: Through a standard S-shaped incision over the
      dorsoulnar aspect of the thumb, one or two 1.5-or 1.3-mm microanchors are fixed
      to the base of the proximal phalanx in the footprint of the avulsed ligament and
      used to suture the proximally based flap after temporary pinning of the MCP
      joint. RESULTS: Stability, range of motion, pinch grip, and radiographs were
      evaluated at least 16 months after surgery. The mean time off work was 10 weeks.
      All patients had equal stability and normal pinch grip when comparing with the
      untreated thumb, allowing all patients to return to preinjury activities,
      including sports, except one (96% of cases). At final follow-up, radiographs
      showed no implant complications, no osteoarthritic changes in MCP joints, and
      stress testing showed that all patients had normal stability in the treated thumb
      when compared with the untreated thumb. Only 2 patients complained of a lumpy
      swelling at the ulnar aspect of the MCP joint, one of which was tender.
      CONCLUSIONS: Repair of UCL of the MCP joint of the thumb with this technique is
      an effective, durable, and safe method to allow restoration and maintenance of a
      stable, pain-free thumb.

PMID- 24126338
TI  - Management of upper limb bone defects using free vascularized osteoseptocutaneous
      fibular bone graft.
AB  - Sixteen patients (11 men and 5 women), who formed the basis of the study,
      underwent surgery in the Hand and Reconstruction Microsurgical Unit, Orthopedic
      Department, Sohag Faculty of Medicine, from January 2001 to January 2009.The
      right side was involved in 7 cases and the left side in 9 cases. Average age was
      35.2 years. The causes of bone defects were infected nonunion of both bone
      forearms in 5 cases, infected nonunion of the middle part of radius in 4 cases,
      posttraumatic bone loss of distal radius in 4 cases, and tumor of shaft humerus
      in 3 cases (aneurysmal bone cyst in 1 and osteosarcoma in 2 patients).The
      principle of treatment was debridement and excision of either infected unhealthy
      bone or tumor tissues with wide safety margin.The average bone defect was 8 cm
      (range, 6-14 cm). The defect was bridged by osteoseptocutaneous vascularized
      fibular bone graft. The donor bone was the right fibula in 7 cases and the left
      fibula in 10 cases. Two grafts were used in 1 patient because of soft tissue
      injuries, which included the peroneal vessels during osteotomy. The vascularized
      fibula was fixed by small dynamic compression plate. The operative time ranged
      between 7 and 11 hours. Blood transfusion was indicated in all the cases and its
      average transfusion was 1000 mL. The average follow-up was 84 months. Bone union
      was ultimately obtained in 15 patients except 1 who had failure of the graft.
      Arthrodesis of the distal ulna with the wrist joint was done during the follow
      up. Arthrodesis of the wrist joint was also performed for 1 patient who had loss
      of carpal bones, distal radius, and wrist and finger extensors. The average time
      for union was 3.5 months. The hand function was normal in all cases. Stress
      fracture and fibular donor-site morbidity did not occur in this series. Neither
      shoulders nor elbows were affected postoperatively. There was no recurrence for
      either infection or tumor. 

PMID- 24126339
TI  - Anterior shoulder release and tendon transfer as 1-stage procedure for treatment
      of internal rotation contracture deformity in obstetric brachial plexus injuries.
AB  - PURPOSE: Children who had internal rotation contracture deformities of the
      shoulder secondary to obstetric brachial plexus palsy were studied. The outcomes
      of anterior shoulder release and tendon transfer in 1-stage procedure were
      analyzed. METHODS: Anterior shoulder release and tendon transfer in 2 separate
      incisions as 1 procedure were performed in 76 patients for improvement of
      shoulder function. Anterior shoulder release was performed through the
      deltopectoral incision, starting with the coracoid process that extended 5 cm
      caudally. Osteotomy of the coracoid process subperiosteally with retaining the
      pectoralis minor attached to the periosteum. Z-plasty of the subscapularis and
      resuturing of the pectoralis minor short head of biceps and coracobrachialis to
      their original position were performed in all cases. A separate second incision
      in the posterior axillary fold was carried out to perform rerouting of the
      latissimus dorsi and teres major tendons with a mean follow-up of 5.6 years
      (range, 1-7 years). RESULTS: The average active external rotation with the arm at
      the side increased from -26 + 15 degrees preoperatively to 67 + 17 degrees
      postoperatively (average gain, 85 degrees). The average shoulder abduction
      increased from 46 + 22 degrees preoperatively to 130 + 32 degrees postoperatively
      (average gain, 75 degrees). Mallet score improved from 12.3 to 22.6. CONCLUSIONS:
      Anterior shoulder release combined with latissimus dorsi and teres major
      rerouting significantly improved global shoulder function.

PMID- 24126340
TI  - Salvage of complicated diaphyseal femoral fractures by 1-stage open debridement
      and Ilizarov technique.
AB  - Infected femoral shaft fractures and femoral nonunions are difficult to manage.
      In the presence of associated segmental bony defects, limb length discrepancy, or
      complex deformities, Ilizarov techniques seem to be the ideal choice for
      management. We would like to describe small case series of 3 patients managed
      using Ilizarov techniques: the first patient with infected nonunion of a femoral
      shaft fracture over an interlocking nail, the second patient with infected
      femoral shaft plating, and the third with longstanding femoral shaft hypertrophic
      nonunion who had multiple surgeries and presented at the end with a broken
      intramedullary nail. The principal management in all cases was a single-stage
      aggressive debridement and fixation using circular Ilizarov external fixator or
      hybrid external fixator followed by either segmental bone transport for the first
      2 patients or monofocal compression distraction for the third patient. The end
      result was clinical and radiological union in all patients with equalization of
      the limb length. 

PMID- 24126341
TI  - Split intravascular stents for side-to-end lymphaticovenular anastomosis.
AB  - Supermicrosurgical lymphaticovenular anastomosis (LVA) is becoming the treatment
      of choice for compression-refractory lymphedema. Among various types of LVA, side
      to-end (S-E) LVA is considered to be the most efficient one, because it can
      divert bidirectional lymph flows into venous circulation via 1 anastomosis, but
      is technically difficult. We developed a new technique for safe and easy S-E LVA
      with modified intravascular stenting (IVaS) method. Different from the original
      IVaS method, a lymphatic vessel is pierced by an IVaS before creation of a
      lateral window. The IVaS is cut after window creation and the ends are inserted
      into the lymphatic vessel and the venule respectively, guiding the course of the
      needle throughout the S-E anastomosis procedure. This method makes S-E LVA easier
      without special instruments. 

PMID- 24126342
TI  - Evolution of abdominal wall reconstruction: development of a unified algorithm
      with improved outcomes.
AB  - INTRODUCTION: Ventral hernia repair (VHR) continues to evolve and now frequently
      includes some form of component separation (CS) for large defects. To determine
      the optimal technique for VHR, we evaluated our outcomes before and after we
      refined and simplified our algorithm for repair. METHODS: One hundred five
      consecutive patients undergoing VHR for large midline hernias over 9 years were
      examined. Patients were divided into those operated on after (group 1) and before
      (group 2) the institution of our simplified algorithm. Our algorithm emphasizes
      careful patient selection and a stepwise approach including, but not limited to,
      bilateral CS if appropriate, preservation of large perforators, retrorectus mesh
      placement as appropriate, linea alba or midline fascial closure, and vertical
      panniculectomy. Primary outcomes evaluated included wound infection, dehiscence,
      and hernia recurrence. RESULTS: Seventy-eight (74.3%) patients underwent repair
      using our algorithm (group 1), whereas 27 (25.7%) underwent repair before
      utilization of this algorithm (group 2). Ninety-eight (93.3%) underwent CS,
      whereas 7 (6.7%) underwent another form of VHR. There was no significant
      difference in patient age or defect size. The mean follow-up period in days for
      patients in group 1 and group 2 were 184.02 and 526.06, respectively (P < 0.001).
      Hernia recurrence in group 1 was 2.6% versus 29.6% in group 2 (P < 0.001). The
      incidence of wound infection in group 1 was 10.3%, whereas that in group 2 was
      33.3% (P < 0.001). The rate of wound dehiscence in group 1 was 17.9% versus 25.9%
      in group 2 (P < 0.001). CONCLUSIONS: Simplifying and unifying our algorithm for
      VHR, notably with utilization of CS, has yielded improved results. Recurrence and
      wound healing complications using this approach are favorable compared with
      published outcomes.

PMID- 24126343
TI  - Indocyanine green velocity: lymph transportation capacity deterioration with
      progression of lymphedema.
AB  - Lymph transportation capacity is a critical function maintaining fluid
      circulation. After pelvic cancer treatments, lymph obstruction at the pelvic
      region leads to abnormal lymph circulation, resulting in lymph pump dysfunction.
      Besides lymph circulation, lymph pump function is important for lymphedema
      evaluation. We assessed and analyzed lymph transportation capacity of secondary
      lower extremity lymphedema patients using indocyanine green (ICG) lymphography
      according to corresponding severity stage. Indocyanine green velocity and transit
      time could evaluate lymph pump function; ICG velocity decreases and transit time
      increases as the lymphedema severity stage progresses. Measurement of ICG
      velocity required 5 minutes after the dye injection, whereas that of transit time
      took more than 1 hour in severe cases. Indocyanine green velocity can be easily
      obtained and is recommended for evaluation of lymph pump function compared with
      transit time. Dynamic ICG lymphography, which evaluates both lymph pump function
      and circulation, plays an important role in comprehensive assessment of
      lymphedema pathophysiology. 

PMID- 24126344
TI  - Effect of reverse chimerism on rejection in clinical transplantation.
AB  - Chimerism may enable allografts to survive when immunosuppressive therapy is
      administered at low levels or is even absent. Reverse chimerism (RC) is focused
      on intragraft chimerism that repopulates the allograft with cells of recipient
      origin. We aimed to identify and analyze current clinical evidence on RC and the
      presence of endothelial RC and tissue-specific RC. A total of 33 clinical reports
      on cardiac, kidney, liver, and lung transplants published between 1972 and 2012
      that focused on RC were included in a systematic review. Liver allografts
      presented with the highest percentage of endothelial RC and lung allografts by
      far the lowest. Tissue-specific RC was present in most of the recipients, but at
      very low levels. There were also cardiac and kidney allografts with chimerism,
      but the functionality of the cells of recipient origin was questionable. We were
      unable to determine whether RC was a trigger for or a result of acute rejection.
      Further clinical research should focus on outcomes to evaluate the clinical
      relevance of this form of chimerism in transplantation. 

PMID- 24126346
TI  - Intimate Partner Violence: Screening and Intervention in the Health Care Setting.

PMID- 24126345
TI  - Noradrenaline acting on astrocytic beta2-adrenoceptors induces neurite outgrowth
      in primary cortical neurons.
AB  - The neurotransmitter noradrenaline (NA) has anti-inflammatory properties and
      promotes expression of neurotrophic factors in the central nervous system (CNS)
      via activation of glial adrenoceptors. Here we examined the ability of
      conditioned media (CM) from NA-treated glial cells to impact upon neuronal
      complexity. Primary rat cortical neurons were treated either directly with NA (1
      10 MUM), or treated with CM from NA-stimulated primary mixed glial cells.
      Neuronal complexity was assessed using Sholl analysis. Exposure of neurons to CM
      from NA-stimulated glial cells increased all indices of neuronal complexity,
      whereas direct exposure of neurons to NA did not. CM from NA-stimulated
      astrocytes, but not microglia, also increased neuronal complexity indicating a
      key role for astrocytes. The beta-adrenergic subtype was implicated in this
      response as the increase was blocked by the beta-adrenoceptor antagonist
      propanolol, but not by the alpha-adrenoceptor antagonist phentolamine. CM from
      glial cells treated with the beta2-adrenoceptor agonists salmeterol and
      clenbuterol, but not the beta1-adrenoceptor agonist xamoterol, mimicked the
      ability of NA to increase neuronal complexity. NA induced expression of a range
      of growth factors (BDNF, NGF-beta, GDNF, FGF-2 and IL-6) in glial cells. In
      addition to this, the phosphatidylinositol 3-kinase (PI3K), mitogen activated
      protein kinase (MAPK) and JAK-STAT signalling pathways are implicated in NA CM
      induced neuritic growth as inhibition of these pathways attenuated NA CM-induced
      neuritic growth. In conclusion, this study indicates a novel role for NA acting
      at glial beta2-adrenoceptors to induce neuritic growth through the expression of
      soluble factors that elicit a neurotrophic action and increase neuronal
      complexity.

PMID- 24126348
TI  - Quantifying the binding strength of U(VI) with phthalimidedioxime in comparison
      with glutarimidedioxime.
AB  - Studies of the complexation of U(vi) with amidoxime-related ligands help in the
      development of efficient sorbents for the extraction of uranium from seawater. In
      the present study, the stability constants of the U(vi) complexes with two
      phthalimidedioxime ligands were determined by potentiometry and
      spectrophotometry, and compared with glutarimidedioxime previously studied.
      Density functional theory calculations were performed to identify the most
      probable protonation sites of the ligand and to help interpret the trend in the
      binding strength of the ligands. The phthalimidedioxime complexes were found to
      be 2-3 orders of magnitude weaker than the corresponding glutarimidedioxime
      complexes, which was attributed to the difference between the ligands in the
      electronic and structural properties. The incorporation of the aromatic ring into
      phthalimidedioxime reduces the electron density on the donor atoms of the ligand
      and makes the imidedioxime moiety less complementary for binding UO2(2+)via its
      equatorial plane. Though weaker than glutarimidedioxime, phthalimidedioxime still
      forms fairly strong U(vi) complexes and can still effectively compete with
      carbonate for the complexation of U(vi) at seawater pH and carbonate
      concentration. Due to its higher chemical stability in acidic solutions than that
      of glutarimidedioxime, phthalimidedioxime is a valuable ligand that could have
      potential use in the extraction of U(vi) from seawater. 

PMID- 24126347
TI  - Maintenance of pluripotency in mouse ES cells without Trp53.
AB  - Tumor suppressor Trp53 works as a guardian of the genome in somatic cells. In
      mouse embryonic stem (ES) cells, it was reported that Trp53 represses
      pluripotency-associated transcription factor Nanog to induce differentiation.
      However, since Trp53-null mice develop to term, Trp53 is dispensable for both the
      maintenance and differentiation of the pluripotent stem cell population in vivo,
      suggesting the differential functions of Trp53 in ES cells and embryos. To reveal
      the basis of this discrepancy, here we established a new line of Trp53-null ES
      cells by sequential gene targeting and evaluated their ability to differentiate
      in vitro and in vivo. We found that Trp53-null ES cells had defects in
      differentiation in vitro as reported previously, whereas they were able to
      contribute to normal development in chimeric embryos. These data indicated that
      the requirement of Trp53 for maintaining and executing the ES pluripotency is not
      absolute. 

PMID- 24126349
TI  - Altered residues in key proteins influence the expression and activity of the
      nitrogenase complex in an adaptive CO2 fixation-deficient mutant strain of
      Rhodobacter sphaeroides.
AB  - Previously, the RubisCO-compromised spontaneous adaptive Rhodobacter sphaeroides
      mutant, strain 16PHC, was shown to derepress the expression of genes that encode
      the nitrogenase complex under normal repressive conditions. As a result of this
      adaptation, the active nitrogenase complex restored redox balance, thus allowing
      strain 16PHC to grow under photoheterotrophic conditions in the absence of an
      exogenous electron acceptor. A combination of whole genome pyrosequencing and
      whole genome microarray analyses was employed to identify possible loci
      responsible for the observed phenotype. Mutations were found in two genes, glnA
      and nifA, whose products are involved in the regulatory cascade that controls
      nitrogenase complex gene expression. In addition, a nucleotide reversion within
      the nifK gene, which encodes a subunit of the nitrogenase complex, was also
      identified. Subsequent genetic, physiological and biochemical studies revealed
      alterations that led to derepression of the synthesis of an active nitrogenase
      complex in strain 16PHC. 

PMID- 24126350
TI  - Spa13 of Shigella flexneri has a dual role: chaperone escort and export gate
      activator switch of the type III secretion system.
AB  - The type III secretion apparatus (T3SA) is used by numerous Gram-negative
      pathogens to inject virulence factors into eukaryotic cells. The Shigella
      flexneri T3SA spans the bacterial envelope and its assembly requires the products
      of ~20 mxi and spa genes. Despite progress made in understanding how the T3SA is
      assembled, the role of several predicted soluble components, such as Spa13,
      remains elusive. Here, we show that the secretion defect of the spa13 mutant is
      associated with lack of T3SA assembly which is partly due to the instability of
      the needle component MxiH. In contrast to its Yersinia counterpart, Spa13 is not
      a secreted protein. We identified a network of interactions between Spa13 and the
      ATPase Spa47, the C-ring protein Spa33, and the inner-membrane protein Spa40.
      Moreover, we revealed a Spa13 interaction with the inner-membrane MxiA and showed
      that overexpression of the large cytoplasmic domain of MxiA in the WT background
      shuts off secretion. Lastly, we demonstrated that Spa13 interacts with the
      cleaved form of Spa40 and with the translocator chaperone IpgC, suggesting that
      Spa13 intervenes during the secretion hierarchy switch process. Collectively, our
      results support a dual role of Spa13 as a chaperone escort and as an export gate
      activator switch. 

PMID- 24126351
TI  - Procedures for fetal neuroprotection: use of magnesium sulfate.

PMID- 24126352
TI  - [Maternal and perinatal outcomes in women with decreased amniotic fluid].
AB  - PURPOSE: To determine maternal and perinatal outcomes in pregnant women with low
      amniotic fluid, according to the amniotic fluid index (AFI). METHODS: A cohort
      study conducted on 176 patients admitted to the high risk ward of Instituto de
      Medicina Integral Prof. Fernando Figueira (IMIP), in Recife, Pernambuco, Brazil.
      Amniotic fluid was measured by the amniotic fluid index, and classified as low
      when between 5.1 and 7.9 cm, moderate oligohydramnios between 3.1 and 5.0 cm, and
      severe oligohydramnios when less than or equal to 3.0 cm. To determine the
      difference between the three groups of categorical variables studied the chi
      square and Fisher exact tests were used, when applicable, and for the numerical
      variables the Mann-Whitney test was applied, with the level of significance set
      at 5%. RESULTS: Fetal malformation more frequently occurred when oligohydramnios
      was severe. Hypertensive disorders, however, were associated with moderate
      oligohydramnios. There was similarity between the three groups in relation to
      premature rupture of membranes and other causes. Low amniotic fluid was more
      frequently diagnosed when tested at the gestational age of 32 weeks or earlier.
      Regarding the perinatal outcomes, the incidence of Apgar score <7 in the 1st and
      5th minutes, perinatal death, neonatal jaundice and pulmonary hypoplasia was
      higher when oligohydramnios was moderate to severe. CONCLUSIONS: Maternal and
      perinatal causes and outcomes in pregnant women with low amniotic fluid vary with
      respect to their AFI, severe oligohydramnios being associated with fetal
      malformation and other adverse perinatal outcomes.

PMID- 24126353
TI  - [Prenatal care and birth weight: an analysis in the context of family health
      basic units].
AB  - PURPOSE: To characterize prenatal care and to evaluate the association of its
      adequacy with maternal, socioeconomic and environmental sanitation
      characteristics, as well as the influence of these factors on the birth weight of
      the children. METHODS: The eligible population for the study consisted of all
      women who had children during 2009 and lived in the city of Queimadas at the time
      of data collection. Information was collected with a questionnaire applied to the
      mothers in Family Health Basic Units or in their residence. The prenatal care
      adequacy index (outcome variable) was defined as adequate when the mother
      attended six or more prenatal visits and began monitoring during the first
      trimester of pregnancy (<20 weeks). Hierarchical logistic regression was
      performed to estimate the odds ratios for inadequate prenatal care and a multiple
      linear regression model was used to estimate the effect of adequacy of prenatal
      care and maternal, socioeconomic and environmental sanitation variables on birth
      weight. The statistical program used was Rv2.10.0, with the level of significance
      set at p <5%. RESULTS: Of a total of 199 women studied, 78.4% were classified as
      having received adequate prenatal care. After adjustment for other predictors,
      maternal age of 19 years or less remained as an explanatory variable of
      inadequate prenatal care (OR 4.27, 95%CI 1.10 - 15.89). Even after controlling
      for variables, child's birth weight was negatively associated with water supply
      from a well/spring and burnt/buried garbage, accounting for weight reductions of
      the order of 563.8, 262.0 and 951.9 g, respectively. CONCLUSION: Adequate
      prenatal care can alleviate the influence of socioeconomic disparities related to
      health care. Even in this situation, teenage mothers are more likely to receive
      inadequate prenatal care and low birth weight is favored by improper sanitation
      conditions (such as water supply and garbage disposal).

PMID- 24126354
TI  - Reference range of uterine artery Doppler parameters between the 11th and 14th
      pregnancy weeks in a population sample from Northeast Brazil.
AB  - PURPOSE: To establish reference values for the first trimester uterine artery
      resistance index (UtA-RI) and pulsatility index (UtA-PI) in healthy singleton
      pregnant women from Northeast Brazil. METHODS: A prospective observational cohort
      study including 409 consecutive singleton pregnancies undergoing routine early
      ultrasound screening at 11 - 14 weeks of gestation was performed. The patients
      responded to a questionnaire to assess maternal epidemiological characteristics.
      The left and right UtA-PI and UtA-RI were examined by color and pulsed Doppler by
      transabdominal technique and the mean UtA-PI, mean UtA-RI and the presence of
      bilateral protodiastolic notching were recorded. Quartile regression was used to
      estimate reference values. RESULTS: The mean +/- standard deviation UtA-RI and
      UtA-PI were 0.7 +/- 0.1 and 1.5 +/- 0.5, respectively. When segregated for
      gestation age, mean UtA-PI was 1.6 +/- 0.5 at 11 weeks, 1.5 +/- 0.6 at 12 weeks,
      1.4 +/- 0.4 at 13 weeks and 1.3 +/- 0.4 at 14 weeks' gestation and mean UtA-RI
      was 0.7 +/- 0.1 at 11 weeks, 0.7 +/- 0.1 at 12 weeks, 0.6 +/- 0.1 at 13 weeks and
      0.6 +/- 0.1 at 14 weeks' gestation. Uterine artery bilateral notch was present in
      261 (63.8%) patients. We observed that the 5th and 95th percentiles of the UtA-PI
      and UtA-RI uterine arteries were 0.7 and 2.3 and, 0.5 and 0.8, respectively.
      CONCLUSION: Normal reference range of uterine artery Doppler in healthy singleton
      pregnancies from Northeast Brazil was established. The 95th percentile of UtA-PI
      and UtA-RI values may serve as a cut-off for future prediction of pregnancy
      complications studies (i.e., pre-eclampsia) in Northeast Brazil.

PMID- 24126355
TI  - [Evaluation of perinatal factors that influence the incidence of necrotizing
      enterocolitis in very low birth weight infants].
AB  - PURPOSE: To evaluate the perinatal factors that influence the incidence of
      necrotizing enterocolitis (NEC) in newborns infants (NBI) weighing less than
      1,500 g. METHODS: A prospective study that analyzed all infants with birth weight
      (BW) less than 1,500 g born between January 2006 to December 2010 (n=183). They
      were divided into two groups, i.e. infants diagnosed with NEC (n=18) and infants
      without a diagnosis of NEC (n=165), which were compared in terms of perinatal
      factors that could influence the incidence of NEC. Mean data were compared by
      Student's t-test or nonparametric tests and percentages of categorical variables
      were compared by the chi2 test. When the variables showed differences between
      groups, they were analyzed using logistic regression with the dependent variable
      as the presence of NEC. The statistical package used was SPSS 16.0 for Windows.
      RESULTS: The two groups were similar in terms of most of the clinical and
      demographic neonatal and maternal data, except for the presence of preeclampsia
      (PE), which was higher in patients whose children developed NEC (61.1 versus
      35,6%). The presence of PE increased the chance of occurrence of NEC by 2.84
      times (95%CI 1.0 - 7.7). CONCLUSION: The only factor that can interfere with the
      incidence of NEC in infants of very low birth weight was the presence of PE.
      Awareness of this fact can guide the perinatal team in providing more judicious
      care regarding the prevention of NEC in this specific population.

PMID- 24126356
TI  - [Facial palsy and pregnancy: management and treatment].
AB  - PURPOSE: To compare the degree of peripheral facial palsy of pregnant women and
      puerperae at admission and at discharge and to evaluate related factors. METHODS:
      Retrospective, cross-sectional study, with analysis of medical records of
      pregnant and postpartum women with facial palsy, over a period of 12 months, with
      application of a standardized protocol for patient evaluation and of the House
      Brackmann scale on the occasion of the first visit and at discharge. RESULTS: Six
      patients were identified, mean age of 22.6 years. Five cases were classified as
      stage IV and one as stage II on the House-Brackmann scale, being two of them
      puerperae and four pregnant. All showed improvement on the House-Brackmann scale.
      CONCLUSION: The Bell's palsy has a good prognosis even in pregnant and postpartum
      women, being important to perform the correct treatment to reduce the sequelae in
      this group identified as more susceptible to peripheral facial palsy.

PMID- 24126357
TI  - [Adequacy of the device intrauterine by ultrasound evaluation: postpartum and
      post-abortion insertion versus insertion during the menstrual cycle].
AB  - PURPOSE: To compare by transvaginal ultrasound the position of the intrauterine
      device (IUD) inside the uterine cavity, depending on the time of insertion,
      postpartum and post-abortion, and during the menstrual cycle. METHODS:
      Epidemiologic, observational and cross-sectional study carried out between
      February and July, 2013. A total of 290 women were included, 205 of them with
      insertion during the menstrual cycle and 85 during the postpartum and post
      abortion periods. The independent variables were: age, parity, time of use,
      insertion time, number of returns to family planning, satisfaction with the
      method, wish to continue using the device, symptoms and complications. The
      dependent variable was the adequate position of the IUD inside the uterine
      cavity. The chi2 test with Pearson's correction and the Fisher exact test were
      used for statistical analysis, with the level of significance set at 5%. RESULTS:
      The average age was 29.4 years and the average time of IUD use was 2.7 years;
      39.3% of the women had symptoms associated with the method, the most frequent
      being menorrhagia (44.7%). The degree of satisfaction was 85% and 61.4% of the
      women returned two or more times for consultation about family planning. Age,
      parity and the position of the uterus in the pelvic cavity was not associated
      with a poor position of the IUD inside the uterine cavity (p>0.05). Insertion
      during the menstrual cycle was significantly more associated with a correct
      position of the IUD than postpartum and post-abortion insertion (p<0.028).
      CONCLUSION: Postpartum and post-abortion insertion showed worse results regarding
      the adequacy of IUD position, a fact that was not observed regarding age, parity
      or position of the uterus in the pelvic cavity.

PMID- 24126358
TI  - [Prevalence of Chlamydia trachomatis and risk factors associated with infection
      detected in endocervical sample].
AB  - PURPOSE: It was to determine the prevalence of Chlamydia trachomatis and the risk
      factors associated with infection in endocervical specimens from women seen in
      outpatient Obstetrics and Gynecology. METHODS: Samples of endocervical secretion
      of 200 women treated at the University Hospital of the Federal University of Rio
      Grande were analyzed for the presence of C. trachomatis by polymerase chain
      reaction (PCR) using primers that amplify CT05/CT06 281 base pairs of the main
      outer membrane protein of C. trachomatis. All participants completed a pre-coded
      and self-report questionnaire. Data were analyzed with the SPSS 17.0 software;
      for multivariate analysis it was used Poisson regression. RESULTS: Of the 200
      women who were included in the study, the prevalence of infection with C.
      trachomatis was 11% (22 patients) and these 55 (27.5%) were positive for HPV.
      Risk factors associated with infection by C. trachomatis were: 8 years or less of
      schooling (p<0.001), family income below the poverty level (p=0.005), first
      intercourse at age 15 or less (p=0.04) and being a carrier of the virus HIV
      (p<0.001). After multivariate analysis, only the variables of schooling or less
      than eight years (PR 6.0; 95%CI 1.26 - 29.0; p=0.02) and presence of HIV (RP
      14.1; 95%CI 3.4 - 57.5; p<0.001) remained statistically significant. CONCLUSIONS:
      The prevalence of C. trachomatis in endocervical specimens by PCR was 11%. The
      factors associated with a higher infection by C. trachomatis were lower education
      and being HIV positive.

PMID- 24126359
TI  - Assessing the impact of HER2 status on the antitumor activity of an HSP90
      inhibitor in human tumor xenograft mice using pharmacokinetic-pharmacodynamic
      modeling.
AB  - The purpose of this study is to assess the impact of human epidermal growth
      factor receptor 2 (HER2) status on the antitumor activity of CH5164840, an orally
      available heat shock protein 90 (HSP90) inhibitor, using pharmacokinetic
      pharmacodynamic modeling. Athymic mice, each implanted with one of eight human
      tumor xenografts, were treated with CH5164840 once daily at doses of 3.13 to 50
      mg/kg. Plasma concentrations of CH5164840 were described by a one-compartment
      model with first-order absorption rate. Time profiles of tumor growth inhibition
      in the eight xenograft models were well captured by an indirect response model
      with a maximum tumor-killing rate constant (Emax model). Threshold plasma
      concentrations for tumor stasis, which are determined by multiple pharmacodynamic
      parameters, Emax, EC50 and tumor growth rate constant, were significantly lower
      in HER2-positive tumors (1.96-3.85 uM) than in HER2-negative tumors (4.48-23.4
      uM). The results suggest that CH5164840 was more efficacious in HER2-positive
      tumors than in HER2-negative tumors in terms of the lower effective concentration
      of the drug in preclinical animal models.

PMID- 24126360
TI  - Reduced heterozygosity at intragenic and flanking microsatellites of pfcrt gene
      establishes natural selection based molecular evolution of chloroquine-resistant
      Plasmodium falciparum in India.
AB  - The positive selection of a nucleotide substitution in exon 2 of Plasmodium
      falciparum chloroquine resistance transporter (pfcrt) gene (mutation responsible
      for chloroquine resistance) causes a reduction in variation of neutral loci close
      to the gene. This reduction in allelic diversity around flanking regions of pfcrt
      gene was reported in worldwide chloroquine resistant isolates and referred as
      selective sweep. In Plasmodium falciparum isolates of India, the selective sweep
      in flanking loci of pfcrt gene is well established, however, high allelic
      diversity observed in intragenic microsatellites of pfcrt gene implied an ongoing
      genetic recombination. To understand, if molecular evolution of chloroquine
      resistant P. falciparum isolates in India follow a selective sweep model, we
      analyzed genetic diversity at both seven intragenic and seven flanking
      microsatellites of pfcrt (-24 to +106kb) gene in chloroquine sensitive and
      resistant parasites originating from high and low transmission areas. We observed
      low expected heterozygosity at all loci of resistant pfcrt-haplotypes (He=0-0.77)
      compared to the wild-type (He=0.38-0.96). Resistant SVMNT from high transmission
      areas showed significantly higher mean He (P=0.03, t-test) at both intragenic and
      pfcrt-flanking loci (-24 to +22 kb) in comparison to low transmission areas. Our
      observation of reduction in variation at both intragenic and flanking loci of
      mutant pfcrt gene confirmed the selective sweep model of natural selection in
      chloroquine resistant P. falciparum isolates in India.

PMID- 24126361
TI  - Differential regulation of TLR mediated innate immune response of mouse neuronal
      cells following infection with novel ECSA genotype of Chikungunya virus with and
      without E1:A226V mutation.
AB  - Chikungunya virus (CHIKV) has received global attention due to the series of
      large-scale outbreaks in different parts of the world including Africa, Indian
      Ocean Islands, India and South-East Asia. The appearance of many unusual severe
      manifestations including neurological disorders was reported in post resurgence
      epidemics with implication of novel East Central South African (ECSA) genotype
      with E1:A226V mutation. The molecular mechanism of CHIKV neuropathogenesis is not
      yet understood and very little is known about the host-pathogen interactions. In
      the present study replication kinetics and innate immune response of ECSA
      genotype of CHIKV with and without A226V mutation were determined in mouse
      neuroblastoma cell line (N2a). The 226V mutant strain was more replication
      competent in N2a cells with a peak titer of 10(8)PFU/ml compared to 10(6)PFU/ml
      for A226 virus. Besides, the 226V mutant virus showed relatively less induction
      of antiviral genes i.e. IFN-beta, OAS-3, MX-2, ISG-15 and Toll like receptors 3
      and 7 as compared to non mutant strain (A226). Further pretreatment of N2a cells
      either with Poly I: C, IFN-beta or TNF-alpha resulted in inhibition of CHIKV
      replication hence confirming the role of TLR mediated innate immune response in
      CHIKV pathogenesis. Differential regulation of TLRs and associated down stream
      antiviral genes might have attributed for increased pathogenesis of the 226V
      mutant novel ECSA genotype of CHIKV during the recent epidemics. 

PMID- 24126362
TI  - Translating clinical trials to clinical practice: outcomes of men with metastatic
      castration resistant prostate cancer treated with docetaxel and prednisone in and
      out of clinical trials.
AB  - BACKGROUND: Multiple factors can influence outcomes of patients receiving
      identical interventions in clinical trials and in routine practice. Here, we
      compare outcomes of men with metastatic castrate-resistant prostate cancer
      (mCRPC) treated with docetaxel and prednisone in routine practice and in clinical
      trials. PATIENTS AND METHODS: We reviewed patients with mCRPC treated with
      docetaxel at Princess Margaret Cancer Centre. Primary outcomes were overall
      survival and PSA response rate. Secondary outcomes were reasons for
      discontinuation and febrile neutropenia. Outcomes were compared for men treated
      in routine practice and in clinical trials, and with data from the TAX 327 study.
      RESULTS: From 2001 to 2011, 438 men were treated, of whom 357 received 3-weekly
      docetaxel as first-line chemotherapy: 314 in routine practice and 43 in clinical
      trials. Trial patients were younger and had better performance status. Median
      survival was 13.6 months [95% confidence interval (95% CI) 12.1-15.1 months] in
      routine practice and 20.4 months (95% CI 17.4-23.4 months, P = 0.007) within
      clinical trials, compared with 19.3 months (95% CI 17.6-21.3 months, P < 0.001)
      in the TAX 327 study. PSA response rates were 45%, 54%, and 53%, respectively (P
      = NS). Reasons for treatment discontinuation were similar although trial patients
      received more cycles (median: 6 versus 8 versus 9.5, P < 0.001). Rates of febrile
      neutropenia were 9.6, 0, and 3% (P < 0.001) while rates of death within 30 days
      of last dose were 4%, 0%, and 3%, respectively (P = NS). CONCLUSIONS: Survival of
      patients with mCRPC treated with docetaxel in routine practice is shorter than
      for men included in trials and is associated with more toxicity.

PMID- 24126363
TI  - Breast density: comparison of chest CT with mammography.
AB  - PURPOSE: To (a) perform a pilot study comparing radiologists' reading of breast
      density at computed tomography (CT) of the chest with breast density readings
      from mammography performed in the same patient and (b) compare a subset of these
      with computer-derived measurements of breast density at CT. MATERIALS AND
      METHODS: The institutional review board waived informed consent for this HIPAA
      compliant retrospective review of mammograms and chest CT scans from 206 women
      obtained within 1 year of each other. Two radiologists with expertise in
      interpreting mammographic and CT findings independently reviewed the mammograms
      and CT scans and classified each case into one of the four breast density types
      defined by the Breast Imaging Reporting and Data System of the American College
      of Radiology. Interreader agreements for the mammographic density types and CT
      density grades were determined by using the Cohen weighted kappa statistic. The
      intrareader correlation coefficient was determined in a subset of CT images. In
      another subset of 40 cases, the agreement of the semiautomated computer-derived
      measurements of breast density with the consensus of the two radiologists was
      assessed. RESULTS: Interreader agreement was higher for the CT density grades
      than for the mammographic density types, with 0.79 (95% confidence interval [CI]:
      0.73, 0.85) versus 0.62 (95% CI: 0.54, 0.70). The intrareader reliability of
      breast density grades on CT images was 0.88. The computer-derived breast density
      measurements agreed with those of the radiologists in 36 (90%) cases. When four
      cases were manually adjusted for the complex anatomy, there was agreement for all
      cases. CONCLUSION: Preliminary results suggest that on further validation, breast
      density readings at CT may provide important additional risk information on CT of
      the chest and that computer-derived measurements may be helpful in such
      assessment.

PMID- 24126364
TI  - Pediatric chest and abdominopelvic CT: organ dose estimation based on 42 patient
      models.
AB  - PURPOSE: To estimate organ dose from pediatric chest and abdominopelvic computed
      tomography (CT) examinations and evaluate the dependency of organ dose
      coefficients on patient size and CT scanner models. MATERIALS AND METHODS: The
      institutional review board approved this HIPAA-compliant study and did not
      require informed patient consent. A validated Monte Carlo program was used to
      perform simulations in 42 pediatric patient models (age range, 0-16 years; weight
      range, 2-80 kg; 24 boys, 18 girls). Multidetector CT scanners were modeled on
      those from two commercial manufacturers (LightSpeed VCT, GE Healthcare, Waukesha,
      Wis; SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). Organ
      doses were estimated for each patient model for routine chest and abdominopelvic
      examinations and were normalized by volume CT dose index (CTDI(vol)). The
      relationships between CTDI(vol)-normalized organ dose coefficients and average
      patient diameters were evaluated across scanner models. RESULTS: For organs
      within the image coverage, CTDI(vol)-normalized organ dose coefficients largely
      showed a strong exponential relationship with the average patient diameter (R(2)
      > 0.9). The average percentage differences between the two scanner models were
      generally within 10%. For distributed organs and organs on the periphery of or
      outside the image coverage, the differences were generally larger (average, 3%
      32%) mainly because of the effect of overranging. CONCLUSION: It is feasible to
      estimate patient-specific organ dose for a given examination with the knowledge
      of patient size and the CTDI(vol). These CTDI(vol)-normalized organ dose
      coefficients enable one to readily estimate patient-specific organ dose for
      pediatric patients in clinical settings. This dose information, and, as
      appropriate, attendant risk estimations, can provide more substantive information
      for the individual patient for both clinical and research applications and can
      yield more expansive information on dose profiles across patient populations
      within a practice.

PMID- 24126365
TI  - Lightweight bilayer barium sulfate-bismuth oxide composite thyroid collars for
      superior radiation protection in fluoroscopy-guided interventions: a prospective
      randomized controlled trial.
AB  - PURPOSE: To test whether newer bilayer barium sulfate-bismuth oxide composite
      (XPF) thyroid collars (TCs) provide superior radiation protection and comfort
      during fluoroscopy-guided interventions compared with standard 0.5-mm lead
      equivalent TCs. MATERIALS AND METHODS: Institutional review board approval and
      written informed consent were obtained for this HIPAA-compliant study, and 144
      fluoroscopy-guided vascular interventions were included at one center between
      October 2011 and July 2012, with up to two operators randomly assigned to wear
      XPF (n = 135) or standard 0.5-mm lead-equivalent (n = 121) TCs. Radiation doses
      were measured by using dosimeters placed outside and underneath the TCs. Wearing
      comfort was assessed at the end of each procedure on a visual analog scale (0
      100, with 100 indicating optimal comfort). Adjusted differences in comfort and
      radiation dose reductions were calculated by using a mixed logistic regression
      model and the common method of inverse variance weighting, respectively. RESULTS:
      Patient (height, weight, and body mass index) and procedure (type and duration of
      intervention, operator, fluoroscopy time, dose-area product, and air kerma) data
      did not differ between the XPF and standard groups. Comfort was assessed in all
      256 measurements. On average, the XPF TCs were 47.6% lighter than the standard
      TCs (mean weight +/- standard deviation, 133 g +/- 14 vs 254 g +/- 44; P < .001)
      and had a significantly higher likelihood of a high level of comfort (visual
      analog scale >90; odds ratio, 7.6; 95% confidence interval: 3.0, 19.2; P < .001).
      Radiation dose reduction provided by the TCs was analyzed in 117 data sets (60 in
      the XPF group, 57 in the standard group). The mean radiation dose reductions (ie,
      radiation protection) provided by XPF and standard TCs were 90.7% and 72.4%, with
      an adjusted mean difference of 17.9% (95% confidence interval: 7.7%, 28.1%; P <
      .001) favoring XPF. CONCLUSION: XPF TCs are a lightweight alternative to standard
      0.5-mm lead-equivalent TCs and provide superior radiation protection during
      fluoroscopy-guided interventions.

PMID- 24126366
TI  - Intracranial calcifications and hemorrhages: characterization with quantitative
      susceptibility mapping.
AB  - PURPOSE: To compare gradient-echo (GRE) phase magnetic resonance (MR) imaging and
      quantitative susceptibility mapping (QSM) in the detection of intracranial
      calcifications and hemorrhages. MATERIALS AND METHODS: This retrospective study
      was approved by the institutional review board. Thirty-eight patients (24 male,
      14 female; mean age, 33 years +/- 16 [standard deviation]) with intracranial
      calcifications and/or hemorrhages diagnosed on the basis of computed tomography
      (CT), MR imaging (interval between examinations, 1.78 days +/- 1.31), and
      clinical information were selected. GRE and QSM images were reconstructed from
      the same GRE data. Two experienced neuroradiologists independently identified the
      calcifications and hemorrhages on the QSM and GRE phase images in two randomized
      sessions. Sensitivity, specificity, and interobserver agreement were computed and
      compared with the McNemar test and k coefficients. Calcification loads and
      volumes were measured to gauge intermodality correlations with CT. RESULTS: A
      total of 156 lesions were detected: 62 hemorrhages, 89 calcifications, and five
      mixed lesions containing both hemorrhage and calcification. Most of these lesions
      (146 of 151 lesions, 96.7%) had a dominant sign on QSM images suggestive of a
      specific diagnosis of hemorrhage or calcium, whereas half of these lesions (76 of
      151, 50.3%) were heterogeneous on GRE phase images and thus were difficult to
      characterize. Averaged over the two independent observers for detecting
      hemorrhages, QSM achieved a sensitivity of 89.5% and a specificity of 94.5%,
      which were significantly higher than those at GRE phase imaging (71% and 80%,
      respectively; P < .05 for both readers). In the identification of calcifications,
      QSM achieved a sensitivity of 80.5%, which was marginally higher than that with
      GRE phase imaging (71%; P = .08 and .10 for the two readers), and a specificity
      of 93.5%, which was significantly higher than that with GRE phase imaging (76.5%;
      P < .05 for both readers). QSM achieved significantly better interobserver
      agreements than GRE phase imaging in the differentiation of hemorrhage from
      calcification (kappa: 0.91 vs 0.55, respectively; P < .05). CONCLUSION: QSM is
      superior to GRE phase imaging in the differentiation of intracranial
      calcifications from hemorrhages and with regard to the sensitivity and
      specificity of detecting hemorrhages and the specificity of detecting
      calcifications.

PMID- 24126367
TI  - Rheumatoid arthritis-associated interstitial lung disease: radiologic
      identification of usual interstitial pneumonia pattern.
AB  - PURPOSE: To determine the accuracy of computed tomography (CT) in identifying the
      histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid
      arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS:
      All patients were enrolled into institutional review board-approved longitudinal
      cohorts at their respective institution, and informed consent was obtained at the
      time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n
      = 69) were collected from three tertiary care centers. Two experienced thoracic
      radiologists independently reviewed the CT scans. The CT pattern was categorized
      as definite UIP, possible UIP, or inconsistent with UIP in accordance with
      published criteria. Findings of biopsies were reviewed by an experienced lung
      pathologist. The sensitivity and specificity of definite CT UIP pattern to
      histopathologic UIP pattern were determined. The agreement between radiologists
      was assessed by calculating a kappa score. RESULTS: The histopathologic UIP
      pattern was present in 42 of 69 (61%) patients. Men were more likely than women
      to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69)
      had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96%
      (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive
      value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95%
      CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement
      between radiologists for definite UIP pattern versus not was 87% (kappa = 0.67, P
      < .0001). CONCLUSION: Definite UIP pattern on a CT scan in RA-ILD is highly
      specific and moderately sensitive for histopathologic UIP pattern. CT can
      therefore help accurately identify the UIP pattern in RA-ILD.

PMID- 24126368
TI  - Detection of prefracture hip lesions in atypical subtrochanteric fracture with
      dual-energy x-ray absorptiometry images.
AB  - PURPOSE: To retrospectively assess how often and how early hip dual-energy x-ray
      absorptiometry (DXA) images show prefracture lesions in patients with atypical
      subtrochanteric fracture (ASF) and determine whether DXA images with assessment
      of prodromal symptoms could be used for early ASF prediction. MATERIALS AND
      METHODS: The retrospective research protocol complied with HIPAA and was
      institutional review board approved, with waiver of informed consent. Among 62
      women with ASF, nine without hip DXA images and seven without clear documentation
      of prodromal symptoms were excluded. Serial DXA images of 52 hips in 46 patients
      were included. Among them, 33 hips were assessed with ipsilateral DXA. For this
      ipsilateral group, each hip was assessed for prodromal symptoms and focal
      cortical changes in the lateral subtrochanteric femur cortex at DXA. Overall and
      cumulative detection rates for prodromal symptoms, DXA, and DXA with prodromal
      symptoms were measured and compared with a general linear model for overall
      detection rate and Cox proportional hazard models for cumulative detection rate.
      Thirty-three representative ipsilateral images and 199 images from subjects
      without fractures were reviewed in random order for prefracture lesions by three
      musculoskeletal radiologists independently, and the performance of DXA in ASF
      prediction was assessed. RESULTS: Overall detection rates for DXA, prodromal
      symptoms, and DXA with prodromal symptoms were 61% (20 of 33), 42% (14 of 33),
      and 73% (24 of 33), respectively, in the ipsilateral group. Overall detection
      rate comparisons showed that DXA with prodromal symptoms was superior to
      prodromal symptoms alone (P = .0377). The cumulative detection rate curve for DXA
      with prodromal symptoms was also superior to that of prodromal symptoms alone (P
      = .0018). Sensitivity and specificity of DXA in ASF prediction ranged from 52%
      (17 of 33) to 58% (19 of 33) and 99% (197 of 199) to 100% (199 of 199),
      respectively. CONCLUSION: Assessment of hip DXA images combined with conventional
      assessment of prodromal symptoms enables detection of more ASFs earlier than
      assessment based on prodromal symptoms alone.

PMID- 24126369
TI  - Unresectable hepatocellular carcinoma: randomized controlled trial of
      transarterial ethanol ablation versus transcatheter arterial chemoembolization.
AB  - PURPOSE: To compare effectiveness of transarterial ethanol ablation (TEA) and
      transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular
      carcinoma and determine whether TEA leads to better overall survival and tumor
      response than TACE. MATERIALS AND METHODS: In this institutional review board
      approved preregistered randomized controlled trial (n = 200), informed consent
      was obtained. Primary outcome was overall survival; secondary outcomes were time
      to progression (TTP), progression-free survival (PFS), tumor response at computed
      tomography, and treatment-related toxicity. Eligible patients were randomized at
      a 1:1 ratio. Treatment included transcatheter delivery of ethiodized oil-ethanol
      mixture (2:1 ratio by volume up to 60 mL) for TEA and cisplatin-ethiodized oil
      emulsion (0.5 mg cisplatin per milliliter up to 30 mg), followed by 1-mm gelatin
      sponge pellets, for TACE. Study was terminated after interim analysis (n = 98);
      90 patients were available for analysis. Overall survival, TTP, and PFS were
      analyzed with Kaplan-Meier method; differences were compared with log-rank test.
      RESULTS: Study was terminated prematurely after interim analysis, which showed no
      difference in overall survival; this was unlikely to change with further patient
      accrual. Median overall survival in TEA and TACE was 24.3 months (95% confidence
      interval [CI]: 12.8, 32.7) and 20.1 months (95% CI: 9.3, 31.2), respectively (P =
      .358). Median TTP and PFS for intralesional progression were longer with TEA than
      TACE (TTP, 34.6 months [95% CI: 28.2, 41] vs 26.05 months [95% CI: 18.7, 33.3];
      PFS, 14.8 months [95% CI: 10.2, 19.5] vs 9.3 months [95% CI: 7.1, 11.5]) (P =
      .028 and 0.029, respectively). Complete response rate on a tumor basis was
      persistently and significantly higher with TEA at 3 months (62 of 88 [70%] vs 39
      of 76 [51%], P = .012), 6 months (64 of 88 [73%] vs 41 of 76 [54%], P = .012),
      and 12 months (66 of 88 [75%] vs 45 of 76 [59%], P = .031). CONCLUSION: Although
      there was no significant difference in overall survival, TEA demonstrated better
      complete tumor response, longer time to intralesional progression, and longer
      PFS.

PMID- 24126371
TI  - Irreversible electroporation ablation: creation of large-volume ablation zones in
      in vivo porcine liver with four-electrode arrays.
AB  - PURPOSE: To prospectively determine optimal parameters with which to achieve
      defined large target zones of coagulation by using irreversible electroporation
      (IRE) with four-electrode arrays and the time needed to achieve this treatment
      effect in an in vivo animal model. MATERIALS AND METHODS: This study was approved
      by the animal care and use committee. Ultrasonography (US)-guided IRE ablation (n
      = 90) was performed in vivo in 69 pig livers with an array of four electrodes (18
      gauge) and an electroporation generator. Cardiac-gated 100-usec IRE pulses were
      applied sequentially between the six sets of electrode pairs at 2250-3000 V.
      Multiple algorithms of energy deposition and electrode configuration were
      studied, including interelectrode spacing (1.5-2.5 cm), number of IRE pulses
      applied consecutively to each electrode pair (10, 20, 50, and 100), and number of
      times per cycle each electrode pair was activated (one to 10). Resultant zones of
      treatment were measured with US 1.5-3 hours after IRE and confirmed at gross and
      histopathologic examination. Data and ablation times were compared to determine
      the optimal algorithms with which to achieve 4-7-cm areas of treatment effect in
      the shortest time possible. In addition, the IRE current applied was correlated
      with ablation size. Data were analyzed by using analysis of variance with
      multiple comparisons, t tests, or nonparametric statistics. RESULTS: For 2.5-cm
      spacing, ablation diameter was increased by increasing either the overall time of
      energy application or the number of cycles of 20 pulses (P < .01 for both). IRE
      application of less than four cycles (or continuous IRE application of 100
      pulses) did not result in contiguous ablation. However, sequentially increasing
      the number of cycles of IRE from four to 10 increased both the electrical current
      applied (from 14.4 A +/- 0.4 to 17.6 A +/- 0.7, P = .0004) and ablation diameter
      (from 5.6 cm +/- 0.3 to 6.6 cm +/- 0.3, P = .001). Although division of
      application into cycles did not alter coagulation at 2.0- and 1.5-cm spacing,
      application of energy to diagonal electrode pairs increased coagulation. Thus,
      one 100-pulse cycle (11.0 minutes +/- 1.4) produced 4.8 cm +/- 0.3 of ablation
      for 2.0-cm spacing with diagonal pairs but only 4.1 cm +/- 0.3 of ablation
      without diagonal pairs (7.5 minutes +/- 1.0, P < .03 for both). CONCLUSION: With
      four-electrode arrays, IRE can create large contiguous zones of treatment effect
      in clinically acceptable ablation times; parameters can be tailored to achieve a
      wide range of ablation sizes. Cyclical deposition of IRE application is
      beneficial, particularly for larger interprobe spacing, most likely owing to
      alterations of electrical conductivity that occur after successive applications
      of IRE energy.

PMID- 24126370
TI  - Intravoxel incoherent motion diffusion-weighted MR imaging for characterization
      of focal pancreatic lesions.
AB  - PURPOSE: To evaluate the diagnostic potential of apparent diffusion coefficient
      (ADC) and intravoxel incoherent motion (IVIM)-derived parameters for
      differentiation of common pancreatic tumors, chronic pancreatitis, and normal
      pancreas and for characterization of the malignancy potential of intraductal
      papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS: The institutional
      review board approved this retrospective study, and informed consent was waived.
      Ninety-three consecutive patients with surgically resected and pathologically
      confirmed pancreatic tumors (39 pancreatic adenocarcinomas [PACs], 17
      neuroendocrine tumors [NETs], and 37 IPMNs), seven patients with chronic
      pancreatitis, and 26 patients with a normal pancreas were included in this study.
      All patients underwent pancreatic 3.0-T magnetic resonance imaging, including
      IVIM diffusion-weighted imaging with 10 b values used (from 0 to 1000 sec/mm(2)).
      The ADC, slow component of diffusion (D(slow)), incoherent microcirculation
      (D(fast)), and perfusion fraction (f) were calculated. Steel-Dwass and Mann
      Whitney U tests were used for comparison. The diagnostic performance of the
      parameters was evaluated by using receiver operating characteristic (ROC)
      analysis with Bonferroni correction. RESULTS: Among ADC- and IVIM-derived
      parameters, D(fast) and f values of PACs were significantly lower than those of
      normal pancreas, chronic pancreatitis, and NETs (all P < .05 in post hoc
      analyses). For differentiation of PACs from NETs, f and D(fast) showed a
      significant difference (P < .0001 for both) and were more useful parameters than
      ADC and D(slow) in ROC analysis (all P < .05). Malignant IPMNs had significantly
      lower ADC and D(slow) values and higher D(fast) and f values when compared with
      benign IPMNs (all P < .05). In ROC analysis, f showed the highest area under the
      ROC curve value for distinguishing malignant from benign IPMNs. CONCLUSION: IVIM
      derived perfusion-related parameters could be helpful for the differentiation of
      common malignant tumors in the pancreas and for distinguishing malignant from
      benign IPMNs. D(fast) and f were more valuable parameters in the differentiation
      of PACs from NETs than were ADC and D(slow).

PMID- 24126372
TI  - Background parenchymal signal enhancement ratio at preoperative MR imaging:
      association with subsequent local recurrence in patients with ductal carcinoma in
      situ after breast conservation surgery.
AB  - PURPOSE: To retrospectively investigate whether the background parenchymal
      features around a tumor at preoperative dynamic contrast material-enhanced
      magnetic resonance (MR) imaging are associated with ipsilateral breast tumor
      recurrence (IBTR)-free survival in patients with ductal carcinoma in situ (DCIS)
      after breast conservation surgery. MATERIALS AND METHODS: The institutional
      review board approved this study, and the requirement for informed consent was
      waived. Between 2004 and 2009, 215 consecutive women with pure DCIS who had
      undergone preoperative dynamic contrast-enhanced MR imaging and curative breast
      conservation surgery were identified. Clinical-pathologic features (age,
      menopausal status, presentation of clinical findings, biopsy method, tumor size,
      nuclear grade, hormonal receptor status, margin status, and adjuvant therapy) and
      MR imaging features (lesion size, background parenchymal enhancement grade,
      fibroglandular density, parenchymal signal enhancement ratio [SER] around the
      tumor, lesion type, and lesion kinetics) were analyzed. A Cox proportional
      hazards model was used to determine the association between MR imaging variables
      and IBTR-free survival after controlling for clinical-pathologic variables.
      Reproducibility of SER measurements was evaluated by using the intraclass
      correlation coefficient. RESULTS: There were 15 of 215 (7.0%) IBTR cases (nine
      DCIS cases and six invasive cases) at a median of 36 months (range, 11-61
      months). Multivariate analysis showed that higher parenchymal SER (hazard ratio
      [HR] = 2.028, P < .001 for reader 1; HR = 1.652, P < .001 for reader 2) and
      larger histologic tumor size (HR = 1.360, P = .009 for reader 1; HR = 1.402, P =
      .006 for reader 2) were independent factors associated with worse IBTR-free
      survival. The intraclass correlation coefficient of SER measurements between two
      readers was 0.852 (95% confidence interval: 0.811, 0.885). CONCLUSION: Higher
      parenchymal SER around the tumor at preoperative dynamic contrast-enhanced MR
      imaging and larger histologic tumor size were independent factors associated with
      worse IBTR-free survival in patients with DCIS after breast conservation surgery.

PMID- 24126374
TI  - Antifungal activity of Copaifera langsdorffii Desf oleoresin against
      dermatophytes.
AB  - Dermatophytoses are mycoses that affect keratinized tissues in both humans and
      animals. The aim of this study was to investigate the antifungal activity of the
      oleoresin extracted from Copaifera langsdorffii Desf. against the strains
      Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton
      mentagrophytes ATCC 11481 and Trichophyton rubrum CCT 5507. The antimicrobial
      activity was determined by minimum inhibitory concentration (MIC) and minimum
      fungicidal concentration (MFC) values. Ketoconazole and terbinafine were used as
      reference drugs. The copaiba oleoresin showed moderate fungicidal activity
      against T. mentagrophytes ATCC 11481 (MIC and MFC = 170 MUg mL-1) and weak
      fungicidal activity against T. rubrum CCT 5507 (MIC = 1,360 MUg mL-1 and MFC =
      2,720 MUg mL-1). There was no activity against M. canis ATCC 32903 and M. gypseum
      ATCC 14683. SEM analysis revealed physical damage and morphological alterations
      such as compression and hyphae clustering in the structure of the fungi exposed
      to the action of the oleoresin. The results stimulate the achievement of in vivo
      assays to confirm the benefits of the application of oleoresin extracted from
      copaiba in the treatment of dermatophytosis, both in humans and in animals. 

PMID- 24126373
TI  - Near-identical segregation of mtDNA heteroplasmy in blood, muscle, urinary
      epithelium, and hair follicles in twins with optic atrophy, ptosis, and
      intractable epilepsy.
AB  - IMPORTANCE: Mitochondrial DNA (mtDNA) disorders have emerged as major causes of
      inherited neurologic disease. Despite being well recognized for more than 2
      decades, the clinical presentation continues to broaden. The phenotypic
      heterogeneity is partly owing to different percentage levels of mutant mtDNA
      heteroplasmy in different tissues, but the factors influencing this are poorly
      understood. OBSERVATIONS: This case report describes monozygotic male twins with
      ptosis, optic atrophy, and recent-onset intractable myoclonic epilepsy. The
      assessment of respiratory chain enzyme activities in the muscle from 1 twin
      revealed a severe and isolated defect involving mitochondrial complex I.
      Mitochondrial DNA sequencing revealed a pathogenic m.14487T>C MTND6 mutation,
      which was present at very high levels of heteroplasmy in muscle (84%) and lower
      levels in blood (15%), urinary epithelium (75%), and buccal mucosa (58%). Of
      particular interest, his identical twin was found to harbor very similar levels
      of the m.14487T>C mutation in his blood, urine, buccal mucosa, and hair follicle
      DNA samples, while the presence of low levels in the mother's tissues confirmed
      maternal transmission. CONCLUSIONS AND RELEVANCE: It was shown that m14487T>C can
      also cause the unusual combination of optic atrophy, ptosis, and
      encephalomyopathy leading to intractable seizures. Near-identical heteroplasmy
      levels in different tissues in both siblings support a nuclear genetic mechanism
      controlling the tissue segregation of mtDNA mutations.

PMID- 24126375
TI  - Flavonoid profile of Saskatoon berries (Amelanchier alnifolia Nutt.) and their
      health promoting effects.
AB  - Flavonoids are a significant group of secondary metabolites in plants. Many of
      these compounds are potent antioxidants, being an important part in food products
      derived from the plants. The current status of research on flavonoid compounds in
      the fruit of Saskatoon berries (Amelanchier alnifolia Nutt.) and their health
      promoting effects, including recommended utilization, are reviewed. The major
      classes of flavonoids in the fruit are flavonols (quercetin and rutin), flavanes
      (proanthocyanidin compounds ranging from dimers through to heptamers and even
      higher polymers) and finally anthocyanins. The flavonoids represented the group
      of polyphenols that mostly contributed to the antioxidant activity of Saskatoon
      berries. High content of the flavoinoids antioxidants in the fruit is responsible
      for the observed anti-inflammatory, antidiadiabetic and chemo-protective effects.

PMID- 24126376
TI  - Enzymatic synthesis of highly fluorescent 8-azapurine ribosides using a purine
      nucleoside phosphorylase reverse reaction: variable ribosylation sites.
AB  - Various forms of purine-nucleoside phosphorylase (PNP) were used as catalysts of
      enzymatic ribosylation of selected fluorescent 8-azapurines. It was found that
      the recombinant calf PNP catalyzes ribosylation of 2,6-diamino-8-azapurine in a
      phosphate-free medium, with ribose-1-phosphate as ribose donor, but the
      ribosylation site is predominantly N7 and N8, with the proportion of N8/N7
      ribosylated products markedly dependent on the reaction conditions. Both products
      are fluorescent. Application of the E. coli PNP gave a mixture of N8 and N9
      substituted ribosides. Fluorescence of the ribosylated 2,6-diamino-8-azapurine
      has been briefly characterized. The highest quantum yield, ~0.9, was obtained for
      N9-beta-d-riboside (lambdamax 365 nm), while for N8-beta-d-riboside, emitting at
      ~430 nm, the fluorescence quantum yield was found to be close to 0.4.
      Ribosylation of 8-azaguanine with calf PNP as a catalyst goes exclusively to N9.
      By contrast, the E. coli PNP ribosylates 8-azaGua predominantly at N9, with
      minor, but highly fluorescent products ribosylated at N8/N7. 

PMID- 24126377
TI  - Comparative analysis of click chemistry mediated activity-based protein profiling
      in cell lysates.
AB  - Activity-based protein profiling uses chemical probes that covalently attach to
      active enzyme targets. Probes with conventional tags have disadvantages, such as
      limited cell permeability or steric hindrance around the reactive group. A tandem
      labeling strategy with click chemistry is now widely used to study enzyme targets
      in situ and in vivo. Herein, the probes are reacted in live cells, whereas the
      ensuing detection by click chemistry takes place in cell lysates. We here make a
      comparison of the efficiency of the activity-based tandem labeling strategy by
      using Cu(I)-catalyzed and strain-promoted click chemistry, different ligands and
      different lysis conditions. 

PMID- 24126378
TI  - Size effect of gold nanoparticles in catalytic reduction of p-nitrophenol with
      NaBH4.
AB  - Gold nanoparticles (Au NPs) were prepared by reducing HAuCl4 with NaBH4. Their
      average particle sizes could be tuned in the range of 1.7 and 8.2 nm, by
      adjusting the amount of NaBH4 used during synthesis. The obtained Au NPs
      (colloids) were then loaded onto a commercial Al2O3 support to prepare Au/Al2O3
      catalysts with tunable Au particle sizes. An optimal pH value (5.9) of the Au
      colloid solution was found to be essential for loading Au NPs onto Al2O3 while
      avoiding the growth of Au NPs. Au NPs and Au/Al2O3 catalysts were tested in the
      reduction of p-nitrophenol with NaBH4. Interestingly, the catalytic activity
      depended on the size of Au NPs, being the highest when the average size was 3.4
      nm. Relevant characterization by UV-Vis, TEM, and XRD was conducted. 

PMID- 24126379
TI  - Assessment of the anti-protozoal activity of crude Carica papaya seed extract
      against Trypanosoma cruzi.
AB  - In order to determine the in vivo activity against the protozoan Trypanosoma
      cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds
      were evaluated compared with a control group of allopurinol. The activity of a
      mixture of the three main compounds (oleic, palmitic and stearic acids in a
      proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid
      previously identified in the crude extract of C. papaya was evaluated at doses of
      100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for
      28 days. A significant reduction (p < 0.05) in the number of blood
      trypomastigotes was observed in animals treated with the evaluated doses of the
      C. papaya extract in comparison with the positive control group (allopurinol 8.5
      mg/kg). Parasitemia in animals treated with the fatty acids mixture was also
      significantly reduced (p < 0.05), compared to negative control animals. These
      results demonstrate that the fatty acids identified in the seed extracts of C.
      papaya (from ripe fruit) are able to reduce the number of parasites from both
      parasite stages, blood trypomastigote and amastigote (intracellular stage). 

PMID- 24126380
TI  - Antimicrobial and selected in vitro enzyme inhibitory effects of leaf extracts,
      flavonols and indole alkaloids isolated from Croton menyharthii.
AB  - Croton species are used in folk medicine in the management of infections,
      inflammation and oxidative stress-related diseases. In order to isolate,
      characterize and evaluate the bioactive constituents of Croton menyharthii Pax
      leaf extracts, repeated column fractionation of the ethyl acetate fraction from a
      20% aqueous methanol crude extract afforded three flavonols identified by NMR (1D
      and 2D) spectroscopic methods as myricetrin-3-O-rhamnoside (myricetrin, 1),
      quercetin-3-O-rhamnoside (2) and quercetin (3) along with an indole alkaloid, (E)
      N-(4-hydroxycinnamoyl)-5-hydroxytryptamine, [trans-N-(p-coumaroyl) serotonin, 4].
      All the compounds are reported from the leaf extract of this plant for the first
      time. The crude extracts, four solvent fractions (hexane, DCM, ethyl acetate and
      butanol) and isolated compounds obtained from the leaves were evaluated for their
      inhibitory effects on selected bacteria, a fungus (Candida albicans),
      cyclooxygenase (COX-2), alpha-glucosidase and acetylcholinesterase (AChE).
      Amongst the compounds, quercetin (3) was the most active against Bacillus
      subtilis and Candida albicans while myricetrin-3-O-rhamnoside (1) and trans-N-(p
      coumaroyl) serotonin (4) were the most active compounds against Escherichia coli,
      Klebsiella pneumonia and Staphylococcus aureus. The inhibitory activity of
      myricetrin-3-O-rhamnoside (1) against COX-2 was insignificant while that of the
      other three compounds 2-4 was low. The AChE inhibitory activity of the alkaloid,
      trans-N-(p-coumaroyl) serotonin was high, with a percentage inhibitory activity
      of 72.6% and an IC50 value of 15.0 ug/mL. The rest of the compounds only had
      moderate activity. Croton menyharthii leaf extracts and isolated compounds
      inhibit alpha-glucosidase at very low IC50 values compared to the synthetic drug
      acarbose. Structure activity relationship of the isolated flavonols 1-3 is
      briefly outlined. Compounds 1-4 and the leaf extracts exhibited a broad spectrum
      of activities. This validates the ethnomedicinal use of the plant in folk
      medicine. 

PMID- 24126381
TI  - Silencing of angiotensin-converting enzyme by RNA interference prevents H9c2
      cardiomyocytes from apoptosis induced by anoxia/reoxygenation through regulation
      of the intracellular renin-angiotensin system.
AB  - Inhibition of the angiotensin-converting enzyme (ACE) attenuated apoptotic
      cardiomyocytes induced by ischemic reperfusion (I/R). However, it is difficult to
      evaluate the effects of inhibition of the intracellular ACE in vivo. The
      objective of this study was to determine whether the apoptosis in H9c2
      cardiomyocytes following anoxia/reoxygenation (A/R) would be improved by the
      silencing of intracellular ACE by RNA interference (RNAi). H9c2 cardiomyocytes
      were subjected to A/R 48 h following transfection with ACE-shRNA plasmid. The
      results showed that the gene silencing of intracellular ACE significantly
      inhibited the decrease of cell viability and the increase of apoptotic H9c2
      cardiomyocytes undergoing A/R. Additionally, the gene silencing of intracellular
      ACE significantly promoted the expression of ACE2, decreased caspase-3 activity
      and Bax levels, and enhanced the expression of Bcl-2 in H9c2 cardiomyocytes
      subjected to A/R. The results suggest that the gene silencing of intracellular
      ACE holds great potential in the treatment of cardiomyocyte apoptosis following
      I/R injury through the regulation of the intracellular renin-angiotensin system,
      thereby regulating the intrinsic pathway of apoptosis. 

PMID- 24126382
TI  - Money, well-being, and loss aversion: does an income loss have a greater effect
      on well-being than an equivalent income gain?
AB  - Higher income is associated with greater well-being, but do income gains and
      losses affect well-being differently? Loss aversion, whereby losses loom larger
      than gains, is typically examined in relation to decisions about anticipated
      outcomes. Here, using subjective-well-being data from Germany (N = 28,723) and
      the United Kingdom (N = 20,570), we found that losses in income have a larger
      effect on well-being than equivalent income gains and that this effect is not
      explained by diminishing marginal benefits of income to well-being. Our findings
      show that loss aversion applies to experienced losses, challenging suggestions
      that loss aversion is only an affective-forecasting error. By failing to account
      for loss aversion, longitudinal studies of the relationship between income and
      well-being may have overestimated the positive effect of income on well-being.
      Moreover, societal well-being might best be served by small and stable income
      increases, even if such stability impairs long-term income growth. 

PMID- 24126383
TI  - Linear correlation between the C-H activation barrier and the C-Cu/C-H bond
      dissociation energy gap in Cu-promoted C-H activation of heteroarenes.
AB  - DFT calculations indicate a linear correlation between the C-H activation barrier
      and the C-Cu/C-H bond dissociation energy gap in Cu-promoted C-H activation of
      heteroarenes. 

PMID- 24126384
TI  - Cigarette smoke extract induces the expression of GRP78 in A549 cells via the
      p38/MAPK pathway.
AB  - Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of
      chronic obstructive pulmonary disease. To determine the involvement of glucose
      regulated protein 78 (GRP78) in the cigarette smoke extract (CSE)-induced
      apoptosis of alveolar epithelial cells and the potential mechanisms underlying
      this effect, A549 cells that originate from alveolar type II epithelial cells
      were exposed to various CSE conditions in the present study. GRP78 expression and
      its effect on the apoptosis of A549 cells were investigated using techniques such
      as RT-PCR, western blot analysis, gene knockdown by GRP78 siRNA interference and
      the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The
      activity of the p38/mitogen-activated protein kinase (MAPK) pathway and its
      involvement in GRP78 expression were also analyzed using SB203580, a p38/MAPK
      pathway inhibitor. It was demonstrated that GRP78 expression in the cells was
      significantly upregulated following CSE exposure and a 12-h exposure of 5% CSE
      was the most efficient in inducing GRP78 expression. This CSE-induced GRP78
      expression was significantly attenuated by GRP78 siRNA or by the use of SB203580.
      The downregulation of GRP78 expression by GRP78 siRNA also led to the increased
      expression of caspase-3 and an increased apoptotic index (AI, P<0.05 vs. other
      groups). These results suggested that CSE induced GRP78 expression in A549 cells.
      This study demonstrated that upregulated GRP78 expression may be anti-apoptotic
      effects and the p38/MAPK pathway was involved in the process of CSE-induced GRP78
      expression in A549 cells.

PMID- 24126385
TI  - Expression of activation-induced cytidine deaminase in Bowenoid papulosis.

PMID- 24126386
TI  - Current technological advances in magnetic resonance with critical impact for
      clinical diagnosis and therapy.
AB  - The last 5 years of technological advances with major impact on clinical magnetic
      resonance (MR) are discussed, with greater emphasis on those that are most
      recent. These developments have already had a critical positive effect on
      clinical diagnosis and therapy and presage continued rapid improvements for the
      next 5 years. This review begins with a discussion of 2 topics that encompass the
      breadth of MR, in terms of anatomic applications, contrast media, and MR
      angiography. Subsequently, innovations are discussed by anatomic category,
      picking the areas with the greatest development, starting with the brain, moving
      forward to the liver and kidney, and concluding with the musculoskeletal system,
      breast, and prostate. Two final topics are then considered, which will likely,
      with time, become independent major fields in their own right, interventional MR
      and MR positron emission tomography (PET).The next decade will bring a new
      generation of MR contrast media, with research focused on substantial
      improvements (>100-fold) in relaxivity (contrast effect), thus providing greater
      efficacy, safety, and tissue targeting. Magnetic resonance angiography will see
      major advances because of the use of compressed sensing, in terms of spatial and
      temporal resolution, with movement away from nondynamic imaging. The breadth of
      available techniques and tissue contrast has greatly expanded in brain imaging,
      benefiting both from the introduction of new basic categories of imaging
      techniques, such as readout-segmented echo planar imaging and 3D fast spin echo
      imaging with variable flip angles, and from new refinements specific to anatomic
      areas, such as double inversion recovery and MP2RAGE. Liver imaging has benefited
      from the development of techniques to easily and rapidly assess lipid, and will
      see, overall, a marked improvement in the next 5 years from new techniques on the
      verge of clinical introduction, such as controlled aliasing in parallel imaging
      results in higher acceleration (CAIPIRINHA), with a substantial impact on both
      spatial resolution and scan time. Renal MR is benefiting from the application of
      blood-oxygen-level-dependent imaging, providing an assessment of renal function
      critical for the evaluation of chronic kidney disease. Techniques to reduce metal
      artifact are a major focus of development in musculoskeletal MR and are critical
      for the ever-increasing postsurgical and implant patient population, leading to
      markedly improved imaging of tissue adjacent to metal and diagnosis of infection,
      prosthesis loosening, and postsurgical complications such as fracture. In breast
      MR, scan techniques are continuing to evolve, and the impact of this examination
      on screening for and evaluation and treatment of breast carcinoma is substantial
      with continued expansion of indications. Prostate MR has benefited from
      multiparametric imaging and the application of diffusion-weighted imaging, the
      latter technique also now applied more generally in body imaging, with a
      substantial clinical impact, in particular for the detection of tumor lymph
      nodes. Interventional MR is still early in its development, although well
      established in many centers, possessing great potential in comparison with
      computed tomography (CT) because of superior soft-tissue contrast, real-time
      multiplanar imaging guidance and monitoring, the availability of temperature
      mapping, and the lack of ionizing radiation. And last but not least, MR-PET is in
      its infancy, with the first round of clinical units installed in the past 2 years
      and early clinical experience showing equivalence and, in some instances,
      superiority to PET-CT. As with the field of MR itself, which began when CT was
      already an established modality, MR-PET will likely, in the next decade, become
      an equivalent modality to PET-CT, if not begin to supplant the latter modality. 

PMID- 24126387
TI  - Guide to the assessment of physical activity: Clinical and research applications:
      a scientific statement from the American Heart Association.
AB  - The deleterious health consequences of physical inactivity are vast, and they are
      of paramount clinical and research importance. Risk identification, benchmarks,
      efficacy, and evaluation of physical activity behavior change initiatives for
      clinicians and researchers all require a clear understanding of how to assess
      physical activity. In the present report, we have provided a clear rationale for
      the importance of assessing physical activity levels, and we have documented key
      concepts in understanding the different dimensions, domains, and terminology
      associated with physical activity measurement. The assessment methods presented
      allow for a greater understanding of the vast number of options available to
      clinicians and researchers when trying to assess physical activity levels in
      their patients or participants. The primary outcome desired is the main
      determining factor in the choice of physical activity assessment method. In
      combination with issues of feasibility/practicality, the availability of
      resources, and administration considerations, the desired outcome guides the
      choice of an appropriate assessment tool. The decision matrix, along with the
      accompanying tables, provides a mechanism for this selection that takes all of
      these factors into account. Clearly, the assessment method adopted and
      implemented will vary depending on circumstances, because there is no single best
      instrument appropriate for every situation. In summary, physical activity
      assessment should be considered a vital health measure that is tracked regularly
      over time. All other major modifiable cardiovascular risk factors (diabetes
      mellitus, hypertension, hypercholesterolemia, obesity, and smoking) are assessed
      routinely. Physical activity status should also be assessed regularly. Multiple
      physical activity assessment methods provide reasonably accurate outcome
      measures, with choices dependent on setting-specific resources and constraints.
      The present scientific statement provides a guide to allow professionals to make
      a goal-specific selection of a meaningful physical activity assessment method.

PMID- 24126388
TI  - Structural basis of allosteric interactions among Ca2+-binding sites in a K+
      channel RCK domain.
AB  - Ligand binding sites within proteins can interact by allosteric mechanisms to
      modulate binding affinities and control protein function. Here we present crystal
      structures of the regulator of K+ conductance (RCK) domain from a K+ channel,
      MthK, which reveal the structural basis of allosteric coupling between two Ca2+
      regulatory sites within the domain. Comparison of RCK domain crystal structures
      in a range of conformations and with different numbers of regulatory Ca2+ ions
      bound, combined with complementary electrophysiological analysis of channel
      gating, suggests chemical interactions that are important for modulation of
      ligand binding and subsequent channel opening.

PMID- 24126389
TI  - Autophagy in the pathogenesis of pulmonary disease.
AB  - Autophagy is a process of lysosomal self-degradation that helps to maintain the
      homeostatic balance between the synthesis, degradation and recycling of cellular
      proteins and organelles. Autophagy does not simply function as the machinery for
      supplying amino acids in response to energy demands, it is an adaptive pathway of
      cytoprotection against cellular stressors, including starvation, reactive oxygen
      species (ROS), endoplasmic reticulum (ER) stress and microbial infection.
      Accordingly, autophagy is considered to be the mediator of a variety of cellular
      processes and cell fates, including cell survival and death, cellular senescence
      and immune responses. Due to the organ-specific role of gas exchange, various
      cell types within the lungs are serially exposed to a diverse array of cellular
      stressors, and growing evidence has revealed the crucial involvement of autophagy
      in the pathogenic processes underlying pulmonary diseases. We herein review
      recent findings regarding the role of autophagy in cellular processes and cell
      fates and summarize the role that autophagy appears to play in the pathogenesis
      of pulmonary diseases. 

PMID- 24126390
TI  - Efficacy of catheter ablation for atrial fibrillation in patients with a
      permanent pacemaker for sick sinus syndrome.
AB  - OBJECTIVE: To study the clinical efficacy of catheter ablation for paroxysmal
      atrial fibrillation (AF) in patients with a permanent pacemaker (PM) for sick
      sinus syndrome (SSS). METHODS: Our prospectively established database of patients
      who underwent circumferential pulmonary vein (PV) ablation for paroxysmal AF was
      retrospectively reviewed. A total of 41 patients with a permanent PM for the
      treatment of SSS (SSS+PM group) and 123 age- and gender-matched control subjects
      (on a 1: 3 basis) without SSS or a permanent PM (no-SSS+no-PM group) were
      included in this study. AF recurrence was defined as the occurrence of confirmed
      atrial tachyarrhythmia lasting more than 30 seconds beyond three months after
      catheter ablation in the absence of any antiarrhythmic treatment. RESULTS: During
      a mean follow-up period of 18.3+/-10.6 months (range 3-30 months), 50 patients
      (30.5%) developed recurrence of AF. The recurrence rate was higher in the SSS+PM
      group than in the no-SSS+no-PM group (43.9% vs. 26.3%, p=0.011). A Cox regression
      analysis adjusted for age, valvular heart disease, left atrial (LA) diameter and
      PV isolation identified only SSS and the use of a PM together as an independent
      predictor of recurrence of AF (hazard ratio 2.02, 95% confidence interval 1.10
      3.69, p=0.023). CONCLUSION: Patients with a permanent PM for SSS are at an
      increased risk of recurrence of AF after catheter ablation.

PMID- 24126391
TI  - Cyclophosphamide-induced cardiotoxicity with a prolonged clinical course
      diagnosed on an endomyocardial biopsy.
AB  - A 31-year-old woman with primary mediastinal large B-cell lymphoma refractory to
      conventional chemotherapy was treated with high-dose chemotherapy containing
      cyclophosphamide (CY). Subsequently, she was treated with auto peripheral blood
      stem cell transplantation. Although a complete remission was obtained, heart
      failure developed two months later. Echocardiography showed an impaired systolic
      function with pericardial effusion. A biopsy of the endomyocardial region from
      the left ventricle demonstrated spotty myocardial hemorrhage and myocardial
      fibrosis with disruption and aggregation of mitochondrial cristae. Based on these
      findings, CY-induced cardiotoxicity was diagnosed. The patient was treated with
      conventional therapy for heart failure, which required approximately one year to
      improve her condition. 

PMID- 24126392
TI  - Rapid progression of Graves' ophthalmopathy despite the administration of
      thiamazole.
AB  - A 42-year-old female with body weight loss, finger tremors and ocular discomfort
      was diagnosed with Graves' disease complicated with ophthalmopathy. Thiamazole
      therapy rapidly improved her hyperthyroidism. However, she was admitted to our
      hospital because her eye symptoms acutely deteriorated over a period of two
      weeks. She had ocular immotility, exposure keratitis, conjunctival edema, severe
      proptosis and visual impairment with a high titer of serum thyroid-stimulating
      antibody (TSAb). Methylprednisolone pulse therapy at a dose of 500 mg/day
      improved her eye symptoms. Although the mechanism of the progression of Graves'
      ophthalmopathy has not yet been elucidated, special attention should be paid to
      the occurrence of ophthalmopathy even after the initiation of thiamazole therapy.

PMID- 24126393
TI  - False-positive radioiodine uptake in a functional ovarian cyst in a patient
      treated with total thyroidectomy for papillary cancer.
AB  - False positive radioiodine uptake following thyroidectomy for differentiated
      thyroid cancer has been reported in some cases. A 42-year-old woman was referred
      for ablative radioiodine treatment six weeks after undergoing total thyroidectomy
      for papillary thyroid carcinoma. Posttherapeutic I-131 scintigraphy showed an
      intense hot spot in the left pelvis. Pelvic computed tomography (CT) revealed a
      benign left ovarian mass such as a functional cyst. After menstruation,
      ultrasonographic imaging demonstrated a shrunken ovarian mass. Therefore, we
      diagnosed the patient with a functional cyst that was influenced by hormonal
      fluctuation. It is believed that this is the first case of false-positive
      radioiodine uptake in a functional ovarian cyst. 

PMID- 24126394
TI  - Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with multiple thin
      walled pulmonary cysts: a case report and review of the literature.
AB  - We herein report a rare case of pulmonary mucosa-associated lymphoid tissue (p
      MALT) lymphoma with multiple cystic lesions. A previously healthy 58-year-old
      Japanese woman visited our hospital for an evaluation of abnormal chest computed
      tomography (CT) findings. Chest CT revealed multiple cystic lesions in both
      lungs, and she was diagnosed as having p-MALT lymphoma based on the pathological
      findings. The patient had no underlying autoimmune diseases. She has not received
      any chemotherapy and has been stable for two years. This case suggests that,
      although rare, the possibility of p-MALT lymphoma should be considered in
      patients with multiple cystic lung diseases. 

PMID- 24126395
TI  - Successful treatment with a combination of electrocautery using wire snares and
      gefitinib in patients with EGFR-mutant lung cancer and central airway
      obstruction.
AB  - One-third of lung cancer patients present with life-threatening central airway
      obstruction (CAO). Two elderly patients were referred to our institution with
      symptoms caused by CAO. In each case, thoracic computed tomography and a
      bronchoscopic examination revealed a tumor obstructing the central airway. The
      tumors were resected endoscopically, and the patients' respiratory and
      performance status remarkably improved. Both patients were diagnosed with an
      advanced stage of lung adenocarcinoma harboring epidermal growth factor receptor
      (EGFR) mutations. They received gefitinib monotherapy, with partial responses
      sustained for more than 12 months. Combination therapy with endoscopic tumor
      resection and gefitinib is beneficial in patients with EGFR-mutant lung cancer
      and CAO. 

PMID- 24126396
TI  - Combined unclassifiable interstitial pneumonia and emphysema: a report of two
      cases.
AB  - We herein report two cases of combined pulmonary fibrosis and emphysema (CPFE),
      whose histological patterns of lung pathology could not be categorized into any
      subset of idiopathic interstitial pneumonias(IIPs). Case 1 was a 62-year-old man,
      who presented with dyspnea on exertion and cough. Case 2 was a 51-year-old man
      with a dry cough. The CT findings of both cases fit the definition of CPFE.
      Surgical lung biopsies of both patients revealed alveolar septal widening due to
      collagen deposition, with emphysema and respiratory bronchiolitis mainly in the
      subpleural parenchyma. These cases suggest that the fibrosis of CPFE includes
      smoking-related interstitial fibrosis other than the known histological patterns
      of IIPs. 

PMID- 24126397
TI  - Primary Sjogren syndrome presenting with hemolytic anemia and pure red cell
      aplasia following delivery due to Coombs-negative autoimmune hemolytic anemia and
      hemophagocytosis.
AB  - A 36-year-old woman presented with hemolytic anemia without a reticulocyte
      response 38 days after delivery. A marked reduction in erythroid cells and an
      increase in macrophages with active hemophagocytosis were noted in the bone
      marrow. While conventional Coombs' tests were negative, the level of red blood
      cell (RBC)-bound immunoglobulin G (IgG) was increased. The patient was diagnosed
      with primary Sjogren syndrome (pSS) based on her symptoms, positive anti-SS-A
      antibodies, Coombs-negative autoimmune hemolytic anemia and pure red cell aplasia
      associated with RBC-bound IgG and hemophagocytosis. The unique presentation was
      considered to be a consequence of immunological derangement associated with pSS,
      pregnancy and delivery. 

PMID- 24126398
TI  - Pseudoperipheral palsy due to infarction in the internal capsule.
AB  - Pseudoperipheral palsy can be caused by cerebral cortical infarctions; however,
      it is rarely caused by lacunar infarctions, including those in the posterior limb
      of the internal capsule. Meanwhile, the somatotopic localization of the
      corticospinal tract in the posterior limb of the internal capsule remains
      unknown. We herein report the case of an 81-year-old Japanese woman who presented
      with a left hand drop. Brain magnetic resonance imaging revealed an acute
      infarction as the causative lesion at the inferior level of the anteromedial
      portion of the posterior limb of the right internal capsule. This case report
      indicates the topography of hand fibers in the internal capsule. 

PMID- 24126399
TI  - Hypokalemic paralysis as a presenting manifestation of primary Sjogren's syndrome
      accompanied by vitamin D deficiency.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease characterized by
      progressive lymphocyte infiltration of the exocrine glands. Overt or latent renal
      tubular acidosis (RTA) is a common extraglandular manifestation of pSS.Vitamin D
      deficiency is associated with autoimmune disorders; however, the potential
      correlation between pSS and vitamin D deficiency is rarely discussed. The current
      patient presented with distal RTA, hypocalcemia, and hypophosphatemia that were
      found to be secondary to both vitamin D deficiency and pSS. In patients diagnosed
      with both distal RTA and vitamin D deficiency, clinicians should consider
      autoimmune diseases such as pSS, as a possible underlying etiology. 

PMID- 24126400
TI  - Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and
      upper airway obstruction.
AB  - Streptococcus pneumoniae is a rare pathogen of sepsis in patients with
      antithyroid drug-induced agranulocytosis. We herein describe a case of
      antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and
      upper airway obstruction. A 27-year-old woman who was previously prescribed
      methimazole for nine months presented with a four-day history of a sore throat.
      She nearly choked and was diagnosed with febrile agranulocytosis. She was
      successfully treated with intubation, intravenous antibiotics and granulocyte
      colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency
      airway management, treatment of sepsis and the administration of granulocyte
      colony-stimulating factor can improve the clinical course of antithyroid drug
      induced pneumococcal sepsis in patients with airway obstruction. 

PMID- 24126401
TI  - Radial mycotic aneurysm complicated with infective endocarditis caused by
      Streptococcus sanguinis.
AB  - Peripheral mycotic aneurysm is a rare complication of infective endocarditis. We
      herein report the case of a 61-year-old man with a mycotic aneurysm in the left
      brachial artery, that appeared during treatment with antibiotics against
      infective endocarditis caused by Streptococcus sanguinis. After confirming the
      collateral blood flow on arteriography, we resected the aneurysm and performed
      valvuloplasty, annuloplasty and coronary artery bypass grafting. The patient has
      been in good condition without complications, such as motor dysfunction or
      neuropathy. 

PMID- 24126402
TI  - Hyperimmunoglobulin E syndrome-like symptoms in a hemodialysis patient who
      developed multiple subcutaneous Staphylococcus aureus abscesses.
AB  - Hyperimmunoglobulin E syndrome (HIES) is sporadically triggered by de novo
      genetic mutations of the signal transducer and activator of transcription 3
      (STAT3). Dialysis patients frequently exhibit HIES-like symptoms including
      elevated IgE levels and recurrent bacterial infections. We herein report the case
      of a 74-year-old man on hemodialysis (HD) who developed marked IgE elevation and
      multiple subcutaneous cold Staphylococcus aureus abscesses. We are the first to
      report that a dialysis patient presented with HIES-like symptoms without the
      characteristic facies or bone and connective tissue abnormalities. A STAT3 gene
      analysis was conducted as part of the differential diagnosis. 

PMID- 24126403
TI  - Intrahepatic arterioportal fistula.

PMID- 24126404
TI  - Anomalous hepatic and pulmonary venous drainages.

PMID- 24126405
TI  - Lung adenocarcinoma presenting with diffuse multiloculated cystic lesions.

PMID- 24126406
TI  - Giant pneumatocele with lung herniation.

PMID- 24126407
TI  - Koilonychia in a patient with subacute iron-deficiency anemia.

PMID- 24126408
TI  - Neurosyphilis presenting as frontal and mesial temporal encephalitis.

PMID- 24126409
TI  - Hemorrhagic Wallenberg syndrome.

PMID- 24126410
TI  - Late-occurring paradoxical reaction masquerading as treatment failure for
      tuberculous adenitis.

PMID- 24126411
TI  - Central nervous system infection caused by cryptococcus.

PMID- 24126412
TI  - Smoking and the renal functional status of patients should be defined clearly in
      order to assess atherosclerosis and metabolic syndrome.

PMID- 24126413
TI  - Response letter regarding the article "significance of the presence of metabolic
      syndrome in patients with asymptomatic arteriosclerosis affecting the aorta and
      the cerebral, extra-cranial carotid and coronary arteries".

PMID- 24126415
TI  - A microfluidic platform for chemical stimulation and real time analysis of
      catecholamine secretion from neuroendocrine cells.
AB  - Release of neurotransmitters and hormones by calcium-regulated exocytosis is a
      fundamental cellular process that is disrupted in a variety of psychiatric,
      neurological, and endocrine disorders. As such, there is significant interest in
      targeting neurosecretion for drug and therapeutic development, efforts that will
      be aided by novel analytical tools and devices that provide mechanistic insight
      coupled with increased experimental throughput. Here, we report a simple,
      inexpensive, reusable, microfluidic device designed to analyze catecholamine
      secretion from small populations of adrenal chromaffin cells in real time, an
      important neuroendocrine component of the sympathetic nervous system and
      versatile neurosecretory model. The device is fabricated by replica molding of
      polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the
      master. Microfluidic inlet channels lead to an array of U-shaped "cell traps",
      each capable of immobilizing single or small groups of chromaffin cells. The
      bottom of the device is a glass slide with patterned thin film platinum
      electrodes used for electrochemical detection of catecholamines in real time. We
      demonstrate reliable loading of the device with small populations of chromaffin
      cells, and perfusion/repetitive stimulation with physiologically relevant
      secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked
      catecholamine secretion was reproducible over multiple rounds of stimulation, and
      graded as expected to different concentrations of secretagogue or removal of
      extracellular calcium. Overall, we show this microfluidic device can be used to
      implement complex stimulation paradigms and analyze the amount and kinetics of
      catecholamine secretion from small populations of neuroendocrine cells in real
      time. 

PMID- 24126416
TI  - Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death
      induction upon temozolomide and quercetin treatment.
AB  - The aim of the present study was to investigate whether silencing of Hsp27 or
      Hsp72 expression in glioblastoma multiforme T98G and anaplastic astrocytoma
      MOGGCCM cells increases their sensitivity to programmed cell death induction upon
      temozolomide and/or quercetin treatment. Transfection with specific siRNA was
      performed for the Hsp gene silencing. As revealed by microscopic observation and
      flow cytometry, the inhibition of Hsp expression was correlated with severe
      apoptosis induction upon the drug treatment studied. No signs of autophagy were
      detected. This was correlated with a decreased mitochondrial membrane potential,
      increased level of cytochrome c in the cytoplasm, and activation of caspase 3 and
      caspase 9. All these results suggest that the apoptotic signal was mediated by an
      internal pathway. Additionally, in a large percentage of cells treated with
      temozolomide, with or without quercetin, granules within the ER system were
      found, which was accompanied by an increased level of caspase 12 expression. This
      might be correlated with ER stress. Quercetin and temozolomide also changed the
      shape of nuclei from circular to "croissant like" in both transfected cell lines.
      Our results indicate that blocking of Hsp27 and Hsp72 expression makes T98G cells
      and MOGGCCM cells extremely vulnerable to apoptosis induction upon temozolomide
      and quercetin treatment and that programmed cell death is initiated by an
      internal signal. 

PMID- 24126417
TI  - Carbamazepine suppresses calpain-mediated autophagy impairment after
      ischemia/reperfusion in mouse livers.
AB  - Onset of the mitochondrial permeability transition (MPT) plays a causative role
      in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing
      reperfusion injury remain disappointing. Autophagy is a lysosome-mediated,
      catabolic process that timely eliminates abnormal or damaged cellular
      constituents and organelles such as dysfunctional mitochondria. I/R induces
      calcium overloading and calpain activation, leading to degradation of key
      autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved
      anticonvulsant drug, has recently been reported to increase autophagy. We
      investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers
      from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo
      I/R, respectively. Cell death, intracellular calcium, calpain activity, changes
      in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial
      membrane potential after I/R were analyzed in the presence and absence of 20 MUM
      CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal
      microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT
      and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed
      that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of
      autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized
      mice demonstrated that CBZ substantially reversed autophagic defects and
      mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium
      overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1
      depletion, defective autophagy, onset of the MPT and cell death after I/R.

PMID- 24126419
TI  - Humeral avulsions of the inferior glenohumeral ligament complex involving the
      axillary pouch in professional baseball players.
AB  - INTRODUCTION: Humeral avulsion of the inferior glenohumeral ligament is a rare
      injury in athletes and can involve different parts of the complex. Axillary pouch
      avulsion, in particular, has only recently been recognized in the literature, but
      has never been described in professional baseball pitchers. MATERIALS AND
      METHODS: A retrospective review of professional baseball players presenting to
      our institution over 5 years was performed. Patients with Bankart lesions or
      fractures were excluded. Preoperative MRI was retrospectively correlated with the
      clinical and arthroscopic findings, as available. RESULTS: Four professional
      baseball pitchers were identified, all who had axillary pouch humeral avulsions
      of the inferior glenohumeral ligament. There was a concomitant avulsion of the
      anterior band in one patient. Associated findings included labral tears (n = 2)
      and partial thickness tear of the rotator cuff (n = 2). Three patients ultimately
      had their axillary pouch avulsions repaired at most recent follow-up.
      CONCLUSIONS: APHAGL lesions can be seen in overhead athletes such as baseball
      pitchers and should be carefully considered as a potential cause of disability.
      Appropriate diagnosis is important to ultimately elucidate the optimal management
      of these lesions.

PMID- 24126420
TI  - [Scientificize the debt].

PMID- 24126418
TI  - Analysis of changes in hepatic gene expression in a murine model of tolerance to
      acetaminophen hepatotoxicity (autoprotection).
AB  - Pretreatment of mice with a low hepatotoxic dose of acetaminophen (APAP) results
      in resistance to a subsequent, higher dose of APAP. This mouse model, termed APAP
      autoprotection was used here to identify differentially expressed genes and
      cellular pathways that could contribute to this development of resistance to
      hepatotoxicity. Male C57BL/6J mice were pretreated with APAP (400mg/kg) and then
      challenged 48h later with 600mg APAP/kg. Livers were obtained 4 or 24h later and
      total hepatic RNA was isolated and hybridized to Affymetrix Mouse Genome MU430_2
      GeneChip. Statistically significant genes were determined and gene expression
      changes were also interrogated using the Causal Reasoning Engine (CRE). Extensive
      literature review narrowed our focus to methionine adenosyl transferase-1 alpha
      (MAT1A), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), flavin-containing
      monooxygenase 3 (Fmo3) and galectin-3 (Lgals3). Down-regulation of MAT1A could
      lead to decreases in S-adenosylmethionine (SAMe), which is known to protect
      against APAP toxicity. Nrf2 activation is expected to play a role in protective
      adaptation. Up-regulation of Lgals3, one of the genes supporting the Nrf2
      hypothesis, can lead to suppression of apoptosis and reduced mitochondrial
      dysfunction. Fmo3 induction suggests the involvement of an enzyme not known to
      metabolize APAP in the development of tolerance to APAP toxicity. Subsequent
      quantitative RT-PCR and immunochemical analysis confirmed the differential
      expression of some of these genes in the APAP autoprotection model. In
      conclusion, our genomics strategy identified cellular pathways that might further
      explain the molecular basis for APAP autoprotection. 

PMID- 24126421
TI  - Bone histomorphometry revisited.
AB  - Bone histomorphometry is defined as a quantitative evaluation of bone micro
      architecture, remodelling and metabolism. Bone metabolic assessment is based on a
      dynamic process, which provides data on bone matrix formation rate by
      incorporating a tetracycline compound. In the static evaluation, samples are
      stained and a semi-automatic technique is applied in order to obtain bone
      microarchitectural parameters such as trabecular area, perimeter and width. These
      parameters are in 2D, but they can be extrapolated into 3D, applying a
      stereological formula. Histomorphometry can be applied to different areas;
      however, in recent decades it has been a relevant tool in monitoring the effect
      of drug administration in bone. The main challenge for the future will be the
      development of noninvasive methods that can give similar information. In the
      herein review paper we will discuss the general principles and main applications
      of bone histomorphometry. 

PMID- 24126422
TI  - Denosumab: recent update in postmenopausal osteoporosis.
AB  - Postmenopausal osteoporosis is a major concern to public health. Fractures are
      the major clinical consequence of osteoporosis and are associated with
      substantial morbidity, mortality and health care costs. Bone strength
      determinants such as bone mineral density and bone quality parameters are
      determined by life-long remodeling of skeletal tissue. Receptor activator of
      nuclear factor-kB ligand (RANKL) is a cytokine essential for osteoclast
      differentiation, activation and survival. Denosumab (Prolia(r)) is a fully human
      monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis,
      being recently approved for the treatment of postmenopausal osteoporosis in women
      at a high or increased risk of fracture by the FDA in the United States and by
      the European Medicines Agency in Europe since June 2010. FREEDOM, DECIDE and
      STAND are the phase 3 trials comparing denosumab with placebo and alendronate in
      postmenopausal osteoporosis. The authors aim to update denosumab role in
      postmenopausal osteoporosis with a physiopathological review.

PMID- 24126423
TI  - [Neonatal lupus erythematosus - review of pathophysiology and clinical
      implications].
AB  - Neonatal lupus erythematosus is a rare disease that can affect different organs,
      mainly the skin and heart. In either asymptomatic pregnant women or with
      autoimmune pathology who carry antibodies directed to Ro/SSA, La/SSB and RNP, the
      transplacentar passage of these autoantibodies after the 16th week of gestation
      may cause transient lesions in target organs. The majority regress as the
      maternal antibodies are cleared from the circulation, except for heart lesions
      where fibrosis can induce definitive lesions. Although the importance of these
      antibodies in the pathophysiology of neonatal lupus is well recognized, their
      presence is not sufficient for the development of the disease and other factors,
      such as genetic and environmental factors, must be recognized. Most
      manifestations are benign and limited. Atrioventricular block is an exception
      because it carries a significant mortality and morbidity, emphasizing the value
      of an early diagnosis. The disease can carry a higher risk of autoimmune disease
      in the child and its mother when asymptomatic. Currently, the main focus of the
      investigation of neonatal lupus erythematosus lies on the search for reliable
      markers that predict the specific involvement of fetal organs and for a safe and
      effective treatment to prevent definitive lesions.

PMID- 24126424
TI  - Falls in Portuguese older people: procedures and preliminary results of the study
      Biomechanics of Locomotion in the Elderly.
AB  - AIM: The aims of this study were to: (1) present preliminary results about the
      evaluation of the procedures (physical activity and functional fitness tests)
      followed in the baseline period of our research program, (2) present a
      preliminary characterization of Portuguese older people regarding
      sociodemographic, health, physical activity (PA) and functional fitness (FF)
      variables (3) identify, within those parameters, the ones which are determinant
      to predict falls in Portuguese older adults. MATERIAL AND METHODS: 647 subjects
      aged over 65 years were randomly recruited in Lisbon and Tagus Valley area.
      Trained interviewers administered: (1) a standardized questionnaire that included
      sociodemographic, health and falls parameters; (2) YPAS questionnaire for PA and
      (3) six FF tests (30sec Chair-Stand and 8 foot Up&Go from SFT battery and items 4
      7 from FAB Scale).Reproducibility and convergent validity of the FF and PA tests
      were determined by ICC and Pearson correlations. Logistic regression analysis was
      used to model fall occurrence considering three different fall groups (non
      fallers (NF - 0 falls), fallers (F - 1 fall) and recurrent fallers (RF - >1
      fall). RESULTS: FF and PA tests showed to have a good convergent validity and
      reproducibility, giving us confidence about the results obtained.Approximately
      37% of the elderly tested fell during the previous year. From these, 41% were RF.
      Our results showed that age is not a risk factor for falling and that health and
      FF variables are the most determinant factors to assess fall risk. CONCLUSION:
      According to the results, falls might not be an inevitable consequence of age,
      but instead, mainly associated with poor health and functionality. Moreover, PA
      seems to play a key role in this process, not only because a higher level of PA
      will lead to a better functionality, but also because PA was found to be a
      protective factor for both episodic and recurrent falls.

PMID- 24126425
TI  - [Pigmented Villonodular Synovitis: a diagnostic challenge. Review of 28 cases].
AB  - OBJECTIVE: Pigmented Villonodular Synovitis (PVNS) is a benign and uncommon
      clinical entity, characterized by excessive proliferation of synovial membrane of
      joints, tendon sheaths and bursas. The objective of this study was to evaluate
      demographic and clinical parameters, diagnostic and treatment procedures and the
      outcome of 28 patients with PVNS. MATERIAL AND METHODS: Retrospective study of
      the histologically proven cases of PVNS, diagnosed between January 1998 and April
      2010 in the Orthopaedics Department of Coimbra University Hospital. Clinical data
      were reviewed for each patient and the following parameters were evaluated:
      gender, age at diagnosis, initial clinical symptoms and site of onset, symptom
      duration, main imaging findings (x-ray and magnetic resonance imaging of the
      involved structure), histological features of the lesion, treatment, follow-up
      duration, evidence of recurrence and time between surgery and recurrence.
      RESULTS: A total of 28 patients with histologically proven PVNS were included.
      The majority of patients were female (53.6%) and the mean age at the time of
      diagnosis was 39.2 +/- 19.1 years (mean +/- SD). The time between onset of
      symptoms and diagnosis was un- known in one patient and, in the other 27
      patients, mean delay in diagnosis was 24.4 +/- 20.5 months (mean +/- SD). The
      knee was the most frequently affected site (75% of the cases). Pain and
      progressive local swelling sensation were the most frequent symptoms at onset (in
      82.1% and 71.4% of the cases, respectively). Joint x-ray identified abnormalities
      in only 17.8% of the patients. Magnetic resonance imaging (MRI) of the affected
      structure identified the presence of synovial membrane proliferation in all cases
      and extra-articular extension of the lesion and bone erosions in 39.1% and 34.8%,
      respectively. Diagnosis was histologically proven in all cases (27 with synovial
      joint origin and 1 with tenosynovial origin). Subtotal synovectomy, total
      synovectomy, local excision of the lesion, synovectomy associated with
      arthroplasty and synovectomy associated with arthrodesis were performed in 53.6%,
      21.4%, 10.7%, 7.1% and 3.6% of the cases, respectively. Local recurrence occurred
      in 25% of the patients, with a mean time of recurrence of 60.8 months after
      surgery. CONCLUSION: In PVNS patients, the non-specific symptoms often contribute
      to a delay in establishing a diagnosis. As in the majority of the reported
      studies, in this study the knee was also the most commonly affected articular
      site. Although the x-ray of the affected joint revealed abnormalities in just a
      few number of patients,MRI identified the presence of synovial membrane
      proliferation in all cases, proving its value in the diagnostic approach to this
      entity. However, only the histological study of the lesion allows establishing a
      definitive diagnosis.

PMID- 24126426
TI  - Ibandronate-associated ischemic colitis: case report.
AB  - Ibandronate is considered to be a safe drug, and the few reported side-effects in
      the digestive system are usually related to the upper gastrointestinal tract.
      Large bowel lesions associated to ibandronate use in humans have not been
      reported. We describe the case of a 52-year-old female with two episodes of lower
      abdominal pain after the intake of oral ibandronate. The second pain episode was
      followed by hematochezia with endoscopic and histological evidence of sigmoid
      ischemia. No other possible causes of colonic ischemia were found. After a short
      hospital admission, there was a complete clinical, endoscopic and histological
      recovery. Ibandronate was withdrawn and the patient reported no further
      gastrointestinal complaints. This is the first reported case of colon bleeding
      related to the use of Ibandronate. 

PMID- 24126427
TI  - [Mandibular osteomyelitis in a patient with ankylosing spondylitis with severe
      axial and peripheral involvement].
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects mainly
      the axial skeletal system, causing pain and functional incapacity. The peripheral
      joint involvement occurs in 30 to 40% of cases. Osteomyelitis of the mandible was
      relatively common before the advent of preventive antibiotic therapy and
      restorative dentistry. Currently, the infection of the facial bones is a rare
      condition, being the odontogenic infection the most responsible for cases with
      mandibular involvement. The authors report the case of a EA patient, with severe
      peripheral involvement, which progressed to osteomyelitis of the jaw, secondary
      to the odontogenic infection due to delay in diagnosis and treatment. 

PMID- 24126428
TI  - Cutaneous manifestations of neonatal lupus: a case report.
AB  - Neonatal Lupus Erythematosus (NLE) is a rare disease associated with placental
      transport of maternal anti-Ro/La and/or anti-U1RNP antibodies into the fetal
      circulation and characterized by cardiac, cutaneous, hematologic and hepatic
      manifestations. The most serious complication of NLE is complete heart block and
      cardiomyopathy. The maternal connective tissue disorder has been systemic lupus
      erythematosus (SLE) or Sjogren syndrome in most cases, however approximately 50%
      of mothers are asymptomatic at the time of diagnosis, testing positive only
      against Ro and/ or U1RNP auto-antibodies. We describe a case of neonatal lupus
      erythematosus and review the clinical and laboratory manifestations of this rare
      disease.

PMID- 24126429
TI  - [Descamative interstitial pneumonia in a patient with undifferentiated connective
      tissue disease].
AB  - A 49 year-old Caucasian male, smoker (15 pack-year), had at the beginning of his
      disease an additive, symmetric polyarthritis, affecting predominantly the small
      joints of the hands, wrists, shoulders and tibiotarsal joints. The autoimmune
      study revealed ANA and anti-ribosomal P protein antibodies positivity. An
      undifferentiated connective tissue disease was diagnosed and treatment with
      deflazacort, naproxen and hydroxychloroquine was begun. Two years later, he
      starts exertional dyspnea, without other respiratory symptoms. A chest high
      resolution computerized tomography scan was performed, evidencing diffuse "ground
      glass" opacities. Respiratory functional study showed low diffusion capacity. The
      bronchoalveolar lavage (BAL) revealed a neutrophilic and eosinophilic (20%)
      alveolitis, which was not associated with peripheral blood eosinophilia. The
      definitive diagnosis was obtained by a surgical lung biopsy, which showed
      features consistent with Descamative Interstitial Pneumonia (DIP). This rare
      entity is referred as a smoke-related disease. The debate about an eventual
      association of DIP with autoimmune diseases and BAL eosinophilia is discussed by
      the authors based on the present clinical case features. 

PMID- 24126430
TI  - [Cervical spine involvement in juvenile idiopathic arthritis].

PMID- 24126431
TI  - The WWOX tumor suppressor gene in endometrial adenocarcinoma.
AB  - Endometrial cancer is a lethal malignancy, the causes of which remain to be
      determined. The aim of the present study, carried out on tumor samples from 79
      patients, was to evaluate the role of the WWOX tumor suppressor gene in
      endometrial adenocarcinoma. The expression levels of WWOX and its protein content
      were assessed in normal endometrium and cancer samples. Quantitative PCR was used
      to assess the correlation between the expression levels of WWOX and the genes
      involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction
      (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription
      regulation (TP73, NCOR1). The relationship between loss of hetero-zygosity (LOH)
      and WWOX mRNA levels was also investigated using high resolution melting. Results
      of the present study demonstrated a positive correlation of WWOX expression with
      BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX
      ratio. The results also showed that loss of heterozygosity at two analyzed loci
      of the WWOX gene is frequent in patients with endometrial cancer and that WWOX
      expression levels are lower in tumor samples than in normal tissue. In
      conclusion, WWOX may be involved in endometrial cancer. 

PMID- 24126432
TI  - [Nalmefene: a novel pharmacotherapeutic option for alcoholism].
AB  - Relapses into alcoholism are becoming more frequent even after long-term
      psychotherapy and social therapy. Previous evidence-based pharmacotherapy was
      limited to administration of acamprosate and the opioid antagonist naltrexone.
      Both forms of therapy have not become well established in Germany. The European
      Medicine Agency (EMA) has now approved a further opioid antagonist, nalmefene
      which is an antagonist of the u-opioid receptor just as naltrexon and is also a
      partial agonist of kappa receptors. The preclinical and clinical investigations
      carried out with nalmefene are presented. It seems to be interesting that in the
      therapy studies relevant to approval, nalmefene was not administered for support
      of abstinence but as an"as needed"medication for reduction of drink volume.

PMID- 24126433
TI  - Apigenin sensitizes colon cancer cells to antitumor activity of ABT-263.
AB  - Apigenin is an edible plant-derived flavonoid that shows modest antitumor
      activities in vitro and in vivo. Apigenin treatment resulted in cell growth
      arrest and apoptosis in various types of tumors by modulating several signaling
      pathways. In the present study, we evaluated interactions between apigenin and
      ABT-263 in colon cancer cells. We observed a synergistic effect between apigenin
      and ABT-263 on apoptosis of colon cancer cells. ABT-263 alone induced limited
      cell death while upregulating expression of Mcl-1, a potential mechanism for the
      acquired resistance to ABT-263. The presence of apigenin antagonized ABT-263
      induced Mcl-1 upregulation and dramatically enhanced ABT-263-induced cell death.
      Meanwhile, apigenin suppressed AKT and ERK activation. Inactivation of either AKT
      or ERK by lentivirus-transduced shRNA or treatment with specific small-molecule
      inhibitors of these pathways enhanced ABT-263-induced cell death, mirroring the
      effect of apigenin. Moreover, the combination response was associated with
      upregulation of Bim and activation of Bax. Downregulation of Bax eliminated the
      synergistic effect of apigenin and ABT-263 on cell death. Xenograft studies in
      SCID mice showed that the combined treatment with apigenin and ABT-263 inhibited
      tumor growth by up to 70% without obvious adverse effects, while either agent
      only inhibited around 30%. Our results demonstrate a novel strategy to enhance
      ABT-263-induced antitumor activity in human colon cancer cells by apigenin via
      inhibition of the Mcl-1, AKT, and ERK prosurvival regulators.

PMID- 24126435
TI  - Lateral spin transfer torque induced magnetic switching at room temperature
      demonstrated by x-ray microscopy.
AB  - Changing and detecting the orientation of nanomagnetic structures, which can be
      used for durable information storage, needs to be developed towards true
      nanoscale dimensions for keeping up the miniaturization speed of modern
      nanoelectronic components. Therefore, new concepts for controlling the state of
      nanomagnets are currently in the focus of research in the field of
      nanoelectronics. Here, we demonstrate reproducible switching of a purely metallic
      nanopillar placed on a lead that conducts a spin-polarized current at room
      temperature. Spin diffusion across the metal-metal (Cu to CoFe) interface between
      the pillar and the lead causes spin accumulation in the pillar, which may then be
      used to set the magnetic orientation of the pillar. In our experiments, the
      detection of the magnetic state of the nanopillar is performed by direct imaging
      via scanning transmission x-ray microscopy (STXM). 

PMID- 24126434
TI  - Redirecting apoptosis to aponecrosis induces selective cytotoxicity to pancreatic
      cancer cells through increased ROS, decline in ATP levels, and VDAC.
AB  - Pancreatic cancer cell lines with mutated ras underwent an alternative form of
      cell death (aponecrosis) when treated concomitantly with clinically achievable
      concentrations of arsenic trioxide, ascorbic acid, and disulfiram (Antabuse;
      AAA). AAA's major effects are mediated through generation of intracellular
      reactive oxygen species (ROS) and more than 50% decline in intracellular ATP. N
      acetyl cysteine and a superoxide dismutase mimetic prevented aponecrosis and
      restored intracellular ATP levels. DIDS (4,4'-diisothiocyanatostilbene-2, 2'
      disulfonic acid), the pan- Voltage-Dependent Anion Channel (VDAC), -1, 2, 3
      inhibitor and short hairpin RNA (shRNA) to VDAC-1 blocked cell death and ROS
      accumulation. In vivo exposure of AAA led to a 62% reduction in mean tumor size
      and eliminated tumors in 30% of nude mice with PANC-1 xenografts. We concluded
      that early caspase-independent apoptosis was shifted to VDAC-mediated "targeted"
      aponecrosis by the addition of disulfiram to arsenic trioxide and ascorbic acid.
      Conceptually, this work represents a paradigm shift where switching from
      apoptosis to aponecrosis death pathways, also known as targeted aponecrosis,
      could be utilized to selectively kill pancreatic cancer cells resistant to
      apoptosis.

PMID- 24126436
TI  - Renal sympathetic denervation therapy in the real world: results from the
      Heidelberg registry.
AB  - INTRODUCTION: Renal sympathetic denervation (RDN) is a novel treatment option in
      patients with treatment-resistant arterial hypertension. A subset of recently
      published randomized and non-randomized trials indicates that RDN leads to
      sustained lowering of blood pressure (BP) under controlled study conditions.
      However, registry data that allow evaluation of safety and efficacy in a real
      world setting are largely missing. METHODS: Sixty-three consecutive patients with
      treatment-resistant hypertension underwent RDN with the radiofrequency-based
      SymplicityTM catheter. As part of our prospective registry, treatment efficacy
      and safety were monitored after 3, 6, and 12 months. RESULTS: At 6 months follow
      up, office systolic BP significantly improved by 19 + 23 mmHg as compared to
      baseline, while diastolic BP values reduced by 6 + 13 mmHg (p < 0.05). One year
      after RDN, office BP levels further improved (26 + 25 mmHg in systolic BP and 9 +
      13 mmHg in diastolic BP, respectively), even though 19 patients had reduced the
      number and/or dosage of antihypertensive agents. The response rate, defined as
      reduction of office systolic BP of >= 10 mmHg, was 73% after 6 months. Baseline
      BP was the only significant predictor of blood pressure response, whereas no
      correlation was found between the number of ablation points and the individual
      changes in office blood pressure. Interestingly, patients with challenging renal
      anatomy profited somewhat less from the procedure than those with "normal" renal
      anatomy. Procedure related adverse events occurred in three patients (4.7%) and
      were limited to vascular access complications. CONCLUSIONS: RDN with the
      SymplicityTM system is safe and effective in patients with treatment-resistant
      hypertension also in a real-world setting.

PMID- 24126437
TI  - B-type natriuretic peptide: distribution in the general population and the
      association with major cardiovascular and coronary events--the Heinz Nixdorf
      Recall Study.
AB  - BACKGROUND: A B-type natriuretic peptide (BNP) threshold of 100 pg/ml is used in
      practice for identification of heart failure, but data about the "normal"
      distribution of BNP in a large population in primary prevention are rare. We
      aimed to characterize the BNP distribution in a healthy subset of a population
      based cohort and to evaluate the association of elevated BNP levels with major
      events. METHODS: In a first step, we determined gender-specific distribution and
      90th percentiles of BNP in participants who were at baseline free from known
      determinants of increased BNP, i.e. cardiovascular disease, hypertension or
      chronic kidney disease. Consecutively, the association of BNP levels above these
      90th percentiles with subsequent cardiovascular and coronary events was assessed
      in the entire cohort. RESULTS: In the BNP-normal sub-sample (n = 1,639), we
      defined gender-specific 90th percentile of BNP (31.3 pg/ml for men, 45.5 pg/ml
      for women). From overall 3,697 subjects (mean age 59.4, 52.4 % female), 194
      subjects developed a major cardiovascular event and 122 myocardial infarction
      during a mean follow-up period of 8.0 +/- 1.5 years. The 90th percentiles derived
      from the normal subset as threshold showed strong associations with major events
      in the entire cohort even after adjusting for traditional risk factors: hazard
      ratio (95% CI): 1.86 (1.37; 2.53), p < 0.0001 for cardiovascular, and 1.77 (1.19;
      2.62), p = 0.005 for coronary events. CONCLUSION: The gender-specific 90th
      percentile of BNP (31 pg/ml for males and 45 pg/ml for females) obtained from a
      BNP-normal sub-sample is associated with incident major cardiovascular and
      coronary events, suggesting that even BNP values lower than 100 pg/ml could imply
      prognostic information in the general population.

PMID- 24126438
TI  - Mitochondrial DNA mutation load: chance or destiny?

PMID- 24126439
TI  - Renal histopathology during experimental septic acute kidney injury and recovery.
AB  - OBJECTIVES: Our understanding of septic acute kidney injury is limited. We
      therefore assessed renal histopathological changes induced by septic acute kidney
      injury and their evolution during recovery. DESIGN: Prospective experimental
      study. SETTING: Physiology Research Institute. SUBJECTS: Twenty-two Merino sheep.
      INTERVENTION: We induced septic acute kidney injury by continuous i.v. infusion
      of Escherichia coli. We studied histology, immunohistochemistry, markers of
      apoptosis, and expression of nitric oxide synthase isoforms and hypoxia-inducible
      factor-1alpha. Analysis was performed on kidneys from normal sheep, sheep with
      septic acute kidney injury, and sheep after recovery from septic acute kidney
      injury. MEASUREMENTS AND MAIN RESULTS: In normal, septic, and recovery sheep,
      respectively, serum creatinine was (median) 82 (interquartile range, 70-85), 289
      (171-477), and 70 (51-91) MUmol/L and renal blood flow was 270 +/- 42, 653 +/-
      210, and 250 +/- 49 mL/min. There were no histological differences between
      baseline, acute kidney injury, and recovery sheep. There was no evidence of
      macrophage or myofibroblast infiltration, no evidence of caspase-3 cleavage to
      suggest activation of apoptotic pathways, and no increase in neutrophil
      gelatinase-associated lipocalin to suggest tubular injury. Similarly,
      quantification of apoptosis revealed no differences between the normal and septic
      groups (normal: median, 3; interquartile range, 0-5 cells per visual field and
      septic acute kidney injury: median, 3.5; interquartile range, 0-8 cells per
      visual field; p = 0.618), but in the recovery group, there was increased
      apoptosis (median, 14; interquartile range, 4-34 cells per visual field; p =
      0.002). Expression of all nitric oxide synthase subtypes increased significantly
      in the renal cortex during septic acute kidney injury but tended to decrease in
      the medulla. Medullary hypoxia-inducible factor gene expression decreased from
      1.00 (95% CI, 0.74-1.36) to 0.26 (95% CI, 0.09-0.76) in recovery (p = 0.0106).
      Both inducible nitric oxide synthase and neuronal nitric oxide synthase
      expressions correlated with renal blood flow. CONCLUSION: The lack of any tubular
      injury or increased apoptosis, the increased expression of all cortical nitric
      oxide synthase isoforms, and the link between inducible nitric oxide synthase and
      neuronal nitric oxide synthase with renal blood flow suggest in this experimental
      model that severe sepsis acute kidney injury can develop in the absence of
      histological or immunohistological changes and may be functional in nature.

PMID- 24126440
TI  - Propofol impairs neurogenesis and neurologic recovery and increases mortality
      rate in adult rats after traumatic brain injury.
AB  - OBJECTIVE: Limited data are available on the influence of sedation for critical
      care therapy with the widely used anesthetic propofol on recovery from acute
      traumatic brain injury. To establish the influence of propofol on endogenous
      neurogenesis and functional recovery after traumatic brain injury, rats were
      sedated with propofol either during or 2 hours after experimental traumatic brain
      injury. DESIGN: Randomized controlled animal study. SETTING: University research
      laboratory. SUBJECTS: One hundred sixteen male Sprague Dawley rats.
      INTERVENTIONS: Mechanical brain lesion by controlled cortical impact.
      MEASUREMENTS AND MAIN RESULTS: This study investigated the dose-dependent
      influence of propofol (36 or 72 mg/kg/hr) either during controlled cortical
      impact induction or in a delayed application protocol 2 hours after experimental
      traumatic brain injury. Infusion of propofol resulted in 1) aggravation of
      neurologic dysfunction, 2) increased 28-day mortality rate, and 3) impaired
      posttraumatic neurogenesis (5-bromo-2-deoxyuridine + NeuN-positive cells).
      Application of propofol during trauma induction afforded a significant stronger
      effect in the high-dose group compared with low-dose propofol. In the posttrauma
      protocol, animals were sedated with sevoflurane during the controlled cortical
      impact injury, and propofol was given after an awake phase. In these animals,
      propofol increased mortality rate and impaired neurologic function and
      neurogenesis compared with animals without delayed propofol anesthesia.
      CONCLUSIONS: The results show that propofol may prevent or limit reparative
      processes in the early-phase postinjury. The results therefore indicate that
      anesthetics may be potentially harmful not only in very young mammalians but also
      in adult animals following acute cerebral injuries. The results provide first
      evidence for an altered sensitivity for anesthesia-related negative effects on
      neurogenesis, functional outcome, and survival in adult rats with brain lesions.

PMID- 24126441
TI  - Hypothermic liquid ventilation prevents early hemodynamic dysfunction and
      cardiovascular mortality after coronary artery occlusion complicated by cardiac
      arrest in rabbits.
AB  - OBJECTIVES: Ultrafast and whole-body cooling can be induced by total liquid
      ventilation with temperature-controlled perfluorocarbons. Our goal was to
      determine whether this can afford maximal cardio- and neuroprotections through
      cooling rapidity when coronary occlusion is complicated by cardiac arrest.
      DESIGN: Prospective, randomized animal study. SETTING: Academic research
      laboratory. SUBJECTS: Male New Zealand rabbits. INTERVENTIONS: Chronically
      instrumented rabbits were submitted to coronary artery occlusion and ventricular
      fibrillation. After 8 minutes of cardiac arrest, animals were resuscitated and
      submitted to a normothermic follow-up (control group) or to 3 hours of mild
      hypothermia induced by total liquid ventilation (total liquid ventilation group)
      or by combination of cold saline infusion and cold blankets application (saline
      group). Coronary reperfusion was permitted 40 minutes after the onset of
      occlusion. After awakening, rabbits were followed up during 7 days. MEASUREMENTS
      AND MAIN RESULTS: Ten animals were resuscitated in each group. In the control
      group, all animals secondarily died of cardiac/respiratory failure (8 of 10) or
      neurological dysfunction (2 of 10). In the saline group, the target temperature
      of 32 degrees C was achieved within 30-45 minutes after cooling initiation. This
      slightly reduced infarct size versus control (41% +/- 16% vs 54% +/- 8% of risk
      zone, respectively; p < 0.05) but failed to significantly improve cardiac output,
      neurological recovery, and survival rate (three survivors, six death from
      cardiac/respiratory failure, and one from neurological dysfunction). Conversely,
      the 32 degrees C temperature was achieved within 5-10 minutes in the total liquid
      ventilation group. This led to a dramatic reduction in infarct size (13% +/- 4%;
      p < 0.05 vs other groups) and improvements in cardiac output, neurological
      recovery, and survival (eight survivors, two deaths from cardiac/respiratory
      failure). CONCLUSIONS: Achieving hypothermia rapidly is critical to improve the
      cardiovascular outcome after cardiac arrest with underlying myocardial
      infarction.

PMID- 24126442
TI  - Effect of intermittent phrenic nerve stimulation during cardiothoracic surgery on
      mitochondrial respiration in the human diaphragm.
AB  - OBJECTIVES: Recent studies have shown that brief periods of mechanical
      ventilation in animals and humans can lead to ventilator-induced diaphragmatic
      dysfunction, which includes muscle atrophy, reduced force development, and
      impaired mitochondrial function. Studies in animal models have shown that short
      periods of increased diaphragm activity during mechanical ventilation support can
      attenuate ventilator-induced diaphragmatic dysfunction but corresponding human
      data are lacking. The purpose of this study was to examine the effect of
      intermittent diaphragm contractions during cardiothoracic surgery, including
      controlled mechanical ventilation, on mitochondrial respiration in the human
      diaphragm. DESIGN: Within subjects repeated measures study. SETTING: Operating
      room in an academic health center. PATIENTS: Five subjects undergoing elective
      cardiothoracic surgery. INTERVENTIONS: In patients (age 65.6 +/- 6.3 yr)
      undergoing cardiothoracic surgery, one phrenic nerve was stimulated hourly (30
      pulses/min, 1.5 msec duration, 17.0 +/- 4.4 mA) during the surgery. Subjects
      received 3.4 +/- 0.6 stimulation bouts during surgery. Thirty minutes following
      the last stimulation bout, samples of diaphragm muscle were obtained from the
      anterolateral costal regions of the stimulated and inactive hemidiaphragms.
      MEASUREMENTS AND MAIN RESULTS: Mitochondrial respiration was measured in
      permeabilized muscle fibers with high-resolution respirometry. State III
      mitochondrial respiration rates (pmol O2/s/mg wet weight) were 15.05 +/- 3.92 and
      11.42 +/- 2.66 for the stimulated and unstimulated samples, respectively (p <
      0.05). State IV mitochondrial respiration rates were 3.59 +/- 1.25 and 2.11 +/-
      0.97 in the stimulated samples and controls samples, respectively (p < 0.05).
      CONCLUSION: These are the first data examining the effect of intermittent
      contractions on mitochondrial respiration rates in the human diaphragm following
      surgery/mechanical ventilation. Our results indicate that very brief periods
      (duty cycle ~1.7%) of activity can improve mitochondrial function in the human
      diaphragm following surgery/mechanical ventilation.

PMID- 24126443
TI  - Soy soluble polysaccharide induces apoptosis in HCT-116 human colon cancer cells
      via reactive oxygen species generation.
AB  - Previous studies have suggested that soy sauce contains specific bioactive
      components and various biological activities of soy sauce have been observed. Soy
      soluble polysaccharide (SSPS), a predominant bioactive compound in soy sauce, has
      numerous pharmacological actions, including anti-inflammatory and
      immunomodulating activities. In the current study, the apoptotic effects of SSPS
      were investigated in HCT-116 human colon cancer cells. Treatment with SSPS
      significantly inhibited cell growth in a concentration-dependent manner by
      inducing apoptosis but not necrosis. This induction was associated with the
      generation of reactive oxygen species (ROS), mitochondrial dysfunction,
      activation of caspases and cleavage of the poly (ADP-ribose) polymerase protein.
      Induction of apoptotic cell death of HCT-116 cells by SSPS showed a correlation
      with the downregulation of members of the inhibitor of apoptosis protein family,
      including X-linked inhibitor of apoptosis protein and antiapoptotic Bcl-2, and
      upregulation of Bax and Bad. Administration of N-acetyl-L-cysteine, a scavenger
      of ROS, significantly decreased SSPS-induced apoptosis. These results indicate a
      critical role of signaling cascades involving a ROS-mediated caspase pathway in
      the anticancer effects of SSPS.

PMID- 24126444
TI  - Scaling up routine HIV testing at specialty clinics: assessing the effectiveness
      of an academic detailing approach.
AB  - INTRODUCTION: Scaling up routine HIV testing represents a key component of the
      National HIV/AIDS Strategy. Barriers to routine HIV testing have limited
      widespread adoption. Although many patients visit specialty care providers, few
      efforts to increase routine HIV testing in specialty care settings have been
      made. We report on use of a survey of barriers to routine testing coupled with
      academic detailing-type educational sessions to increase routine testing at
      specialty clinics in Chicago's main safety-net health system. METHODS: We devised
      a survey to assess specialty provider knowledge, attitudes, and barriers to
      routine HIV testing. We administered this at 3 specialty clinics. Each clinic's
      survey responses informed content for academic detailing-type presentations to
      each clinic's medical providers. We provide descriptive statistics summarizing
      survey responses. We report changes in the HIV testing rates and use logistic
      regression to examine associations between time period and odds of testing at
      each clinic. RESULTS: Specialty clinic providers demonstrated varying knowledge
      regarding routine HIV testing guidelines-with trauma providers having the least
      knowledge. Concerns regarding arranging follow-up for patients with positive
      results was the most cited barrier to testing. Two of the 3 specialty clinics
      experienced significant increases in routine HIV testing, whereas the third
      specialty service, which uses more rotating residents, had downtrending routine
      testing rates. DISCUSSION: The increase in routine HIV testing in 2 of 3
      specialty services suggests that academic detailing-type interventions can
      improve routine testing uptake in public safety-net specialty care settings and
      may represent a useful component to incorporate into system-wide scale-up
      efforts.

PMID- 24126445
TI  - Barriers and facilitators of linkage to HIV primary care in New York City.
AB  - One in 5 people living with HIV are unaware of their status; they account for an
      estimated 51% of new infections. HIV transmission can be reduced through a "Test
      and Treat" strategy, which can decrease both viral load and risk behaviors.
      However, linkage of newly diagnosed HIV-positive persons to care has proved
      challenging. We report quantitative and qualitative data on linkage to care from
      HIV testing sites that partnered with the New York City Department of Health and
      Mental Hygiene to implement "The Bronx Knows" (TBK), an initiative that tested
      607,570 residents over 3 years. During TBK, partner agencies reported the
      aggregate number of HIV tests conducted, the number of confirmed positives
      (overall and new), and the number of confirmed positives linked to medical care.
      We conducted qualitative interviews with directors of 24 of 30 TBK HIV testing
      agencies to identify linkage barriers and selected 9 for case studies. Barriers
      to linkage fell into 3 domains: (1) health care system factors (long wait for
      provider appointments, requirement of a positive confirmatory test before
      scheduling an appointment, system navigation, and disrespect to patients); (2)
      social factors (HIV stigma); and (3) characteristics of risk populations (eg,
      mental illness, homelessness, substance use, and immigrant). Best practices for
      linkage included networking among community organizations, individualized care
      plans, team approach, comprehensive and coordinated care services, and patient
      peer navigation. Research and public health implications are discussed.

PMID- 24126446
TI  - Linkage to HIV care in San Francisco: implications of measure selection.
AB  - In this article, we describe a process of the San Francisco collaboration to
      select optimal measures of linkage to care in response to the Enhanced
      Comprehensive HIV Prevention Planning program of the Centers for Disease Control
      and Prevention and to understand the implications of measure selection and the
      challenges of accessing data sources to measure outcomes along the HIV care
      continuum. Challenges identified are the variety of definitions of linkage to
      care and the nonintegrative nature of the multiple data systems necessary to
      measure linkage to care and other continuum outcomes. The choice of linkage
      measures, which at the extremes is a choice between higher-resolution measures
      based on clinical visit data in a subset of patients vs. a lower-resolution proxy
      measure based on surveillance data, has key implications. Choosing between the
      options needs to be informed by the primary use of the measure. For representing
      trends in the overall performance and response to interventions, more
      generalizable measures based on surveillance data are optimal. For identifying
      barriers to linkage to care for specific populations and potential intervention
      targets within the linkage process, higher-resolution measures of linkage that
      include clinical, laboratory, and social work visit information are optimal.
      Cataloging the different data systems along the continuum and observations of
      challenges of data sharing between the systems highlighted the promise of
      integrated data management systems that span HIV surveillance and care systems.
      Such integrated data management systems would have the ability to support
      detailed investigation and would provide simplified data to match newly
      developed, cross-agency Health and Human Service measures of HIV care continuum
      outcomes.

PMID- 24126447
TI  - Behind the cascade: analyzing spatial patterns along the HIV care continuum.
AB  - BACKGROUND: Successful HIV treatment as prevention requires individuals to be
      tested, aware of their status, linked to and retained in care, and virally
      suppressed. Spatial analysis may be useful for monitoring HIV care by identifying
      geographic areas with poor outcomes. METHODS: Retrospective cohort of 1704 people
      newly diagnosed with HIV identified from Philadelphia's Enhanced HIV/AIDS
      Reporting System in 2008-2009, with follow-up to 2011. Outcomes of interest were
      not linked to care, not linked to care within 90 days, not retained in care, and
      not virally suppressed. Spatial patterns were analyzed using K-functions to
      identify "hot spots" for targeted intervention. Geographic components were
      included in regression analyses along with demographic factors to determine their
      impact on each outcome. RESULTS: Overall, 1404 persons (82%) linked to care; 75%
      (1059/1404) linked within 90 days; 37% (526/1059) were retained in care; and 72%
      (379/526) achieved viral suppression. Fifty-nine census tracts were in hot spots,
      with no overlap between outcomes. Persons residing in geographic areas identified
      by the local K-function analyses were more likely to not link to care [adjusted
      odds ratio 1.76 (95% confidence interval: 1.30 to 2.40)], not link to care within
      90 days (1.49, 1.12-1.99), not be retained in care (1.84, 1.39-2.43), and not be
      virally suppressed (3.23, 1.87-5.59) than persons not residing in the identified
      areas. CONCLUSIONS: This study is the first to identify spatial patterns as a
      strong independent predictor of linkage to care, retention in care, and viral
      suppression. Spatial analyses are a valuable tool for characterizing the HIV
      epidemic and treatment cascade.

PMID- 24126448
TI  - "Working together to reach a goal": MSM's perceptions of dyadic HIV care for same
      sex male couples.
AB  - INTRODUCTION: Same-sex serodiscordant male dyads represent a high-priority risk
      group, with approximately one to two thirds of new HIV infections among men who
      have sex with men attributable to main partnerships. Early initiation and
      adherence to highly active antiretroviral therapy is a key factor in HIV
      prevention and treatment; however, adherence to highly active antiretroviral
      therapy in the United States is low, with poor retention throughout the continuum
      of care. This study examines the perceptions of dyadic HIV treatment of men who
      have sex with men across the continuum of care to understand the preferences for
      how care may be sought with a partner. METHODS: We conducted 5 focus group
      discussions in Atlanta, GA, with 35 men who reported being in same-sex male
      partnerships. Participants discussed perceptions of care using scenarios of a
      hypothetical same-sex male couple who recently received serodiscordant or
      seroconcordant HIV-positive results. Verbatim transcripts were segmented
      thematically and systematically analyzed to examine patterns in responses within
      and between participants and focus group discussions. RESULTS: Participants
      identified the need for comprehensive dyadic care and differences in care for
      seroconcordant HIV-positive versus serodiscordant couples. Participants described
      a reciprocal relationship between comprehensive dyadic care and positive
      relationship dynamics. This combination was described as reinforcing commitment,
      ultimately leading to increased accountability and treatment adherence.
      DISCUSSION: Results indicate that the act of same-sex male couples "working
      together to reach a goal" may increase retention to HIV care across the continuum
      if care is comprehensive, focuses on both individual and dyadic needs, and
      promotes positive relationship dynamics.

PMID- 24126449
TI  - Early evidence from California on transitions to a reformed health insurance
      system for persons living with HIV/AIDS.
AB  - BACKGROUND: Many uninsured people living with HIV/AIDS (PLWHA) will obtain
      managed health insurance coverage when the Affordable Care Act (ACA) is
      implemented in January 2014. Since 2011, California has transitioned PLWHA to
      Medicaid managed care (MMC) and to the Low-Income Health Program (LIHP).
      OBJECTIVES: To draw lessons for the ACA implementation from the transitions into
      MMC and the LIHP. METHODS: Surveys about clients and services provided before and
      after the transition to MMC and the LIHP were sent to 43 HIV service providers.
      Usable responses were obtained from 18 (42%). RESULTS: Although total client
      loads were similar in the pre- (January 2011) and posttransition periods (June
      2012), many clients transitioned from fee-for-service (FFS) Medicaid to MMC. Over
      this period, responding agencies served 43.5% fewer PLWHA in FFS Medicaid,
      whereas the share of PLWHA covered by MMC rose from 16.9% to 55.5%. Managed care
      covered a smaller number of services than either FFS Medicaid or Ryan White
      sites. Ryan White providers reported that 53% of the clients they served in
      January 2011 had transitioned to the LIHPs. Nonetheless, they continued to
      provide services to many of these clients, and Ryan White caseloads did not
      decline. CONCLUSIONS: PLWHA enrolled in the MMC continue to depend on Ryan White
      sites to supply the full range of services that will allow them to take full
      advantage of increased access to care under ACA.

PMID- 24126450
TI  - HIV medical providers' perceptions of the use of antiretroviral therapy as
      nonoccupational postexposure prophylaxis in 2 major metropolitan areas.
AB  - INTRODUCTION: In 2005, the Centers for Disease Control and Prevention expanded
      its recommendation of postexposure prophylaxis (PEP) use in the workplace to
      include nonoccupational exposures (nPEP). The availability and extensive use of
      nPEP have not achieved widespread acceptance among health-care providers of high
      risk populations, and public health and primary care agencies have been sparse in
      their implementation of nPEP promotion, protocols, and practices. METHODS: We
      conducted a survey of HIV providers (n = 142, response rate = 61%) in Miami-Dade
      County (Florida) and the District of Columbia that focused on their knowledge,
      attitudes, beliefs, and practices related to the delivery of nPEP. We then
      analyzed differences in survey responses by site and by history of prescribing
      nPEP using bivariate and multivariate logistic regression. RESULTS: More District
      of Columbia providers (59.7%) reported ever prescribing nPEP than in Miami
      (39.5%, P < 0.048). The majority of practices in both cities did not have a
      written nPEP protocol and rarely or never had patients request nPEP.
      Multivariable analysis for history of prescribing nPEP was dominated by having
      patients request nPEP [odds ratio (OR) = 21.53] and the belief that nPEP would
      lead to antiretroviral resistance (OR = 0.14) and having a written nPEP protocol
      (OR = 7.49). DISCUSSION: Our findings are consistent with earlier studies showing
      the underuse of nPEP as a prevention strategy. The significance of having a
      written nPEP protocol and of patient requests for nPEP speaks to the importance
      of using targeted strategies to promote widespread awareness of the use of HIV
      antiretroviral medications as a prevention intervention.

PMID- 24126451
TI  - Assessing HIV testing and linkage to care activities and providing academic
      support to public health authorities in Houston, TX.
AB  - BACKGROUND: Health departments often have little knowledge of HIV testing and
      linkage activities outside of those they directly fund. Many health departments
      also have limited access to outside academic expertise. METHODS: We conducted a
      survey of health organizations in the Houston/Harris County region to determine
      the number of HIV tests completed in 2011, activities that organizations
      conducted to promote linkage to care for persons newly diagnosed with HIV, and
      barriers to linkage to care. We also convened a Scientific Advisory Council to
      advise the local health department on HIV prevention activities. RESULTS: In
      2012, 55 of 84 organizations (65.5%) completed the survey and 43 of those 55
      organizations reported conducting HIV testing, so were included in this analysis.
      Organizations reported conducting 210,565 HIV tests in 2011 and 50.9% under
      health department contract. The median number of tests per organization was 1045
      (interquartile ratio: 159-3520). More than 90% of the organizations used active
      linkage to care methods, but only 46.5% had written linkage to care protocols.
      Barriers to linkage to care most often reported were client refusal followed by
      staff capacity and funding limitations. The Scientific Advisory Council provided
      valuable informal expertise to the local health department. CONCLUSIONS: Half of
      the HIV testing in the Houston/Harris County region is conducted without local
      health department funding, and half the organizations conducting HIV testing have
      linkage to care protocols. The findings of the study and Scientific Advisory
      Council advice have helped the health department with policy, procedures,
      evaluation tools, and technical assistance offerings.

PMID- 24126452
TI  - Dystrophic epidermolysis bullosa pruriginosa in a mother and daughter
      successfully treated by low dose cyclosporine.

PMID- 24126453
TI  - Disruption of glutamate receptor-interacting protein in nucleus accumbens
      enhances vulnerability to cocaine relapse.
AB  - Trafficking and stabilization of AMPA receptors at synapses in response to
      cocaine exposure is thought to be critical for expression of cocaine addiction
      and relapse. Glutamate receptor-interacting protein (GRIP) is a neuronal
      scaffolding protein that stabilizes GluA2 AMPARs at synapses but its role in
      cocaine addiction has not been examined. The current study demonstrates that
      conditional deletion of GRIP within the nucleus accumbens potentiates cue-induced
      reinstatement of cocaine seeking without affecting operant learning, locomotor
      activity, or reinstatement of natural reward seeking. This is the first study to
      demonstrate a role for accumbal GRIP in behavior. Electrophysiological recordings
      revealed increased rectification of AMPAR-mediated currents in the nucleus
      accumbens and increased AMPAR sensitivity to the GluA2-lacking AMPAR antagonist,
      1-naphthylacetyl spermine, indicative of an increased contribution of GluA2
      lacking calcium-permeable AMPARs. In addition, accumbal GRIP deletion was
      associated with blunted long-term depression, similar to what is seen following
      cocaine self-administration. Taken together, these results indicate that GRIP may
      modulate addictive phenotypes through its regulation of synaptic AMPARs by
      controlling their subunit composition and susceptibility to LTD. These effects
      are associated with changes in vulnerability to cocaine relapse and highlight
      GRIP as a novel target for the development of cocaine addiction therapeutics. 

PMID- 24126455
TI  - The peer review congresses: improving peer review and biomedical publication.

PMID- 24126454
TI  - Aversive learning in adolescents: modulation by amygdala-prefrontal and amygdala
      hippocampal connectivity and neuroticism.
AB  - Neuroticism involves a tendency for enhanced emotional and cognitive processing
      of negative affective stimuli and a propensity to worry and be anxious. It is
      known that this trait modulates fear learning and the activation of brain regions
      involved in it such as the amygdala, hippocampus, and prefrontal cortex and their
      connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents
      participated in functional magnetic resonance imaging (fMRI) of aversive
      pavlovian differential delay conditioning. An unpleasant sound served as
      unconditioned stimulus (US) and pictures of neutral male faces as conditioned
      stimuli (CS+ followed by the US in 50% of the cases; CS- never followed by the
      US). During acquisition (CS+/- differentiation), higher levels of neuroticism
      were associated with a stronger interaction between the right amygdala and the
      right hippocampus as well as the right amygdala and prefrontal cortical regions,
      specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and
      anterior cingulate cortex. The association of stronger conditionability of fear
      and connectivity of brain regions related to consolidation of fear associations
      and neuroticism points to underlying mechanisms of the enhanced propensity for
      anxiety disorders in highly neurotic participants. This is especially important
      in adolescence, a vulnerable time for the onset of mental disorders such as
      anxiety disorders. 

PMID- 24126456
TI  - The histamine H4 receptor mediates inflammation and Th17 responses in preclinical
      models of arthritis.
AB  - OBJECTIVE: The histamine H4 receptor (H4R) has been shown to drive inflammatory
      responses in models of asthma, colitis and dermatitis, and in these models it
      appears to affect both innate and adaptive immune responses. In this study, we
      used both H4R-deficient mice and a specific H4R antagonist, JNJ 28307474, to
      investigate the involvement of the H4R in mouse arthritis models. METHODS: H4R
      deficient mice and wild-type mice administered the H4R antagonist were studied in
      models of collagen antibody-induced arthritis (CAIA) and collagen-induced
      arthritis (CIA). The impact on Th17 cells was assessed by restimulation of
      inguinal lymphocytes in the disease or immunisation models and with in vitro
      stimulation of whole blood. RESULTS: Both H4R-deficient mice and mice treated
      with the H4R antagonist exhibited reduced arthritis disease severity in both CAIA
      and CIA models. This was evident from the reduction in disease score and in joint
      histology. In the CIA model, treatment with the H4R antagonist reduced the number
      of interleukin (IL)-17 positive cells in the lymph node and the total production
      of IL-17. Th17 cell development in vivo was reduced in H4R-deficient mice or in
      mice treated with an H4R antagonist. Finally, treatment of both mouse and human
      blood with an H4R antagonist reduced the production of IL-17 when cells were
      stimulated in vitro. CONCLUSIONS: These results implicate the H4R in disease
      progression in arthritis and in the production of IL-17 from Th17 cells. This
      work supports future clinical exploration of H4R antagonists for the treatment of
      rheumatoid arthritis.

PMID- 24126457
TI  - International recommendations for the assessment of autoantibodies to cellular
      antigens referred to as anti-nuclear antibodies.
AB  - Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune
      diseases, and have been determined by indirect immunofluorescence assay (IIFA)
      for decades. As the demand for ANA testing increased, alternative techniques were
      developed challenging the classic IIFA. These alternative platforms differ in
      their antigen profiles, sensitivity and specificity, raising uncertainties
      regarding standardisation and interpretation of incongruent results. Therefore,
      an international group of experts has created recommendations for ANA testing by
      different methods. Two groups of experts participated in this initiative. The
      European autoimmunity standardization initiative representing 15 European
      countries and the International Union of Immunologic Societies/World Health
      Organization/Arthritis Foundation/Centers for Disease Control and Prevention
      autoantibody standardising committee. A three-step process followed by a Delphi
      exercise with closed voting was applied. Twenty-five recommendations for
      determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific
      antibodies (19-23) and validation of methods (24-25) were created. Significant
      differences between experts were observed regarding recommendations 24-25
      (p<0.03). Here, we formulated recommendations for the assessment and
      interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a
      reference method, and the importance of defining nuclear and cytoplasmic
      staining, were emphasised, while the need to incorporate alternative automated
      methods was acknowledged. Various approaches to overcome discrepancies between
      methods were suggested of which an improved bench-to-bedside communication is of
      the utmost importance. These recommendations are based on current knowledge and
      can enable harmonisation of local algorithms for testing and evaluation of ANA
      and related autoantibodies. Last but not least, new more appropriate
      terminologies have been suggested. 

PMID- 24126459
TI  - Transfection activity and the mechanism of pDNA-complexes based on the hybrid of
      low-generation PAMAM and branched PEI-1.8k.
AB  - Cationic polymers have been regarded as promising non-viral gene carriers because
      of their advantages over viral gene vectors, such as low cost, a high level of
      safety and easy manipulation. However, their poor transfection efficiency in the
      presence of serum and high toxicity are still limiting issues for clinical
      applications. In addition, the lack of adequate understanding of the gene
      delivery mechanism hinders their development to some extent. In this study, new
      polycations (PAPEs) consisting of a low generation polyamidoamine (PAMAM) core
      and branched polyethyleneimine (PEI-1.8k) outer layers were synthesized and their
      transfection activity and mechanism were studied. PAPEs were characterized by
      FTIR, (1)H NMR and gel permeation chromatography. PAPEs were able to self
      assemble with pDNA and form spherical nanoparticles with sizes of 70-204 nm and
      zeta potentials of 13-33 mV. Importantly, the PAPE-pDNA complexes displayed lower
      cytotoxicity and higher transfection activity than PEI 25k in various cell lines,
      specifically in the presence of serum. The transfection mechanism was evaluated
      by endocytosis inhibition with specific inhibitors, time-dependent transfection,
      and intracellular trafficking inspection by CLSM. The high levels of transgene
      expression mediated by PAPEs were attributed to caveolae-mediated cellular
      uptake, the reduced entry into lysosomes and the entry into the nucleus through
      mitosis. 

PMID- 24126460
TI  - Spectrophotometric and ultrasensitive DNA bioassay by circular-strand
      displacement polymerization reaction.
AB  - We demonstrated a new spectrophotometric DNA detection approach based on a
      circular strand-displacement polymerization reaction for the quantitative
      detection of sequence specific DNA. In this assay, the hybridization of an
      immobilized hairpin probe on the microtiter plate, to target DNA, results in a
      conformational change and leads to a stem separation. A short primer thus anneals
      with the open stem and triggers a polymerization reaction, allowing a cyclic
      reaction comprising the release of target DNA and hybridization of the target
      with the remaining immobilized hairpin probe. Through this cyclical process, a
      large number of duplex DNA complexes are produced. Finally, the biotin modified
      duplex DNA products can be detected via the HRP catalyzed substrate 3,3',5,5'
      tetramethylbenzidine using a spectrophotometer. As a proof of concept, a short
      DNA sequence (20-nt) related to the South East Asia (SEA) type deletion of alpha
      thalassemia was chosen as the model target. This proposed assay has a very high
      sensitivity and selectivity with a dynamic response ranging from 0.1 fM to 10 nM
      and the detection limit was 8 aM. It can be performed within 2 hours, and it can
      differentiate target SEA DNA from wild-type DNA. By substituting the hairpin
      probes used in the present work, this assay can be used to detect other subtypes
      of genetic disorders. 

PMID- 24126462
TI  - A conceptual framework for managing modifiable risk factors for cardiovascular
      diseases in Fiji.
AB  - AIMS: The current review will look at modifiable lifestyle (physical inactivity,
      poor nutrition, risky alcohol behavior and cigarette smoking) and cardio
      metabolic (obesity, diabetes mellitus, high cholesterol and high blood pressure)
      cardiovascular disease (CVD) risk factors among Indigenous-Fijian and Indo-Fijian
      subgroups. A framework for monitoring and managing these risk factors will be
      presented. METHODS: National health surveys were identified where available.
      Electronic databases identified sources for filling missing data. The most
      relevant data were identified, organized and synthesized. RESULTS: Compared to
      Indo-Fijians, Indigenous-Fijians have higher rates of obesity (17% vs 11%) and
      hypertension (21% vs 16%), but lower rates of diabetes mellitus (12% vs 21%) and
      high cholesterol (33% vs 39%). Indigenous-Fijians report higher rates of
      prescribed physical activity (25% vs 21%), but poorer recommended vegetable
      intake (48% vs 56%), greater risky alcohol behavior (17% vs 15%) and a much
      greater prevalence of cigarette smoking (45% vs 24%). Both Indigenous-Fijians and
      Indo-Fijians report a low prevalence of recommended fruit intake (17% vs 15%).
      CONCLUSIONS: Fiji is progressing through demographic and epidemiological
      transitions, including a decline in infectious diseases and improved life
      expectancy. However, in concert with other developing nations, 'modernization' is
      accompanied by increased mortality from non-communicable diseases, with CVD being
      the most prevalent. This transition has been associated with changes to socio
      cultural aspects of Fiji, including poor lifestyle choices that may contribute to
      a cluster of cardio-metabolic conditions which precede CVD.

PMID- 24126463
TI  - Evaluation and management of pulseless pink/pale hand syndrome coexisting with
      supracondylar fractures of the humerus in children.
AB  - Elbow region fractures are the most common injuries in children. Among them,
      supracondylar fractures of the humerus are the most frequent. Massive
      displacement of the fractured bone causes severe injury to the soft tissue of
      that particular region. As a result, various types of injuries to the brachial
      artery such as entrapment, laceration, spasm of the vessel, and the presence of
      an intimal tear or thrombus formation are usually observed. The main goal of this
      study was to present our approach to children with supracondylar humerus
      fractures associated with brachial artery injuries. We would especially like to
      emphasize the necessity for other conservative or operative treatment concerning
      pulseless hand symptoms coexisting with supracondylar fractures of the humeral
      bone in children population. Data from 67 children were evaluated in our study.
      Supracondylar fractures were classified according to the Gartland's scale. All
      patients had displaced extension type III injuries. During our follow-up study,
      we used Flynn's grading system to evaluate functions of the elbow joint, forearm
      and wrist. Mean follow-up was 18 months; range, 13 months to 4 years. In the
      follow-up study, very good or good results were achieved in all 32 patients
      treated conservatively together with 6 patients with pulseless pink hand symptom.
      Very good or good results were achieved in 88% of 35 patients operated on.
      Children who, after satisfactory closed reduction, have a well-perfused hand but
      absent radial pulse do not necessarily require routine exploration of the
      brachial artery. Conservative treatment should be applied unless additional signs
      of vascular compromise appear. Thus, exploration of the cubital fossa should be
      performed only if circulation is not restored by closed reduction.

PMID- 24126465
TI  - Churg-Strauss syndrome: an uncommon cause of intracerebral hemorrhage.

PMID- 24126464
TI  - Increased killing of SCCVII squamous cell carcinoma cells after the combination
      of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3
      activity and ceramide synthase 1 upregulation.
AB  - Photodynamic therapy (PDT) is not always effective as an anticancer treatment,
      therefore, PDT is combined with other anticancer agents for improved efficacy.
      The combination of dasatinib and PDT with the silicone phthalocyanine
      photosensitizer Pc 4 was assessed for increased killing of SCCVII mouse squamous
      cell carcinoma cells, a preclinical model of head and neck squamous cell
      carcinoma, using apoptotic markers and colony formation as experimental end
      points. Because each of these treatments regulates the metabolism of the
      sphingolipid ceramide, their effects on mRNA levels of ceramide synthase, a
      ceramide-producing enzyme, and the sphingolipid profile were determined. PDT +
      dasatinib induced an additive loss of clonogenicity. Unlike PDT alone or PDT +
      dasatinib, dasatinib induced zVAD-fmk-dependent cell killing. PDT or dasatinib
      induced caspase-3 activation was potentiated after the combination. PDT alone
      induced mitochondrial depolarization, and the effect was inhibited after the
      combination. Annexin V+ and propidium iodide+ cells remained at control levels
      after treatments. In contrast to PDT alone, dasatinib induced upregulation of
      ceramide synthase 1 mRNA, and the effect was enhanced after the combination.
      Dasatinib induced a modest increase in C20:1- and C22-ceramide but had no effect
      on total ceramide levels. PDT increased the levels of 12 individual ceramides and
      total ceramides, and the addition of dasatinib did not affect these increases.
      PDT alone decreased substantially sphingosine levels and inhibited the activity
      of acid ceramidase, an enzyme that converts ceramide to sphingosine. The data
      suggest that PDT-induced increases in ceramide levels do not correlate with
      ceramide synthase mRNA levels but rather with inhibition of ceramidase. Cell
      killing was zVAD-fmk-sensitive after dasatinib but not after either PDT or the
      combination and enhanced cell killing after the combination correlated with
      potentiated caspase-3 activation and upregulation of ceramide synthase 1 mRNA but
      not the production of ceramide. The data imply potential significance of the
      combination for cancer treatment.

PMID- 24126466
TI  - Wohlfahrtiimonas larvae sp. nov., isolated from the larval gut of Hermetia
      illucens (Diptera: Stratiomyidae).
AB  - A novel, Gram-negative, facultative anaerobic, motile and short rod-shaped
      bacterium, strain KBL006(T) was isolated from the larval gut of Hermetia
      illucens, Black soldier fly. The 16S rRNA gene sequence of strain KBL006(T)
      showed 96.4 % similarity to that of Wohlfahrtiimonas chitiniclastica S5(T).
      Strain KBL006(T) grew optimally at 30  degrees C, at pH 8.0 and in the presence
      of 1-2 % (w/v) NaCl. Oxidase activity and catalase activity were positive. The
      major fatty acids were C18:1 omega7c, C14:0, and C16:0. The major respiratory
      quinone was ubiquinone-8 (Q-8). The major polar lipids were
      phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol, and
      two phospholipids. The G+C content of the genomic DNA was 45.2 mol%. Based on
      these polyphasic data, strain KBL006(T) is considered to represent a novel
      species in the genus Wohlfahrtiimonas, for which the name Wohlfahrtiimonas larvae
      sp. nov. is proposed. The type strain is KBL006(T) (= KACC 16839(T) = JCM
      18424(T)). 

PMID- 24126467
TI  - Nonomuraea shaanxiensis sp. nov., a novel actinomycete isolated from a soil
      sample.
AB  - A novel actinomycete, strain NEAU-st1(T), was isolated from a soil sample
      collected in Shaanxi province, Northwest China and characterized using a
      polyphasic approach. 16S rRNA gene sequence similarity studies showed that strain
      NEAU-st1(T) belongs to the genus Nonomuraea, being most closely related to
      Nonomuraea rosea GW12687(T) (98.91 %), Nonomuraea solani NEAU-Z6(T) (98.44 %),
      Nonomuraea rhizophila YIM67092(T)(98.24 %) and Nonomuraea monospora PT708(T)
      (98.02 %); similarities to sequences of other type strains of the genus
      Nonomuraea were lower than 98 %. Both tree-making algorithms used also supported
      the position that strain NEAU-st1(T) formed a distinct clade with its most
      closely related species. Morphological and physiological characteristics
      confirmed that the strain belongs to the genus Nonomuraea and distinguished it
      from its most closely related species. DNA-DNA hybridization further
      differentiated strain NEAU-st1(T) from its nearest phylogenetic neighbours. These
      results suggested that strain NEAU-st1(T) represents a novel species of the genus
      Nonomuraea, for which the name Nonomuraea shaanxiensis sp. nov. is proposed. The
      type strain is NEAU-st1(T) (=CGMCC 4.7096(T) = DSM 45877(T)). 

PMID- 24126469
TI  - The new UEMS-EACCME criteria for accreditation of live educational events (LEEs):
      another step forward to improve the quality of continuing medical education (CME)
      in Europe.

PMID- 24126468
TI  - Diffusion and perfusion correlates of the 18F-MISO PET lesion in acute stroke:
      pilot study.
AB  - PURPOSE: Mapping the ischaemic penumbra in acute stroke is of considerable
      clinical interest. For this purpose, mapping tissue hypoxia with (18)F
      misonidazole (FMISO) PET is attractive, and is straightforward compared to (15)O
      PET. Given the current emphasis on penumbra imaging using diffusion/perfusion MR
      or CT perfusion, investigating the relationships between FMISO uptake and
      abnormalities with these modalities is important. METHODS: According to a
      prospective design, three patients (age 54-81 years; admission NIH stroke scale
      scores 16-22) with an anterior circulation stroke and extensive penumbra on CT-
      or MR-based perfusion imaging successfully completed FMISO PET, diffusion
      weighted imaging and MR angiography 6-26 h after stroke onset, and follow-up
      FLAIR to map the final infarction. All had persistent proximal occlusion and a
      poor outcome despite thrombolysis. Significant FMISO trapping was defined voxel
      wise relative to ten age-matched controls and mapped onto coregistered maps of
      the penumbra and irreversibly damaged ischaemic core. RESULTS: FMISO trapping was
      present in all patients (volume range 18-119 ml) and overlapped mainly with the
      penumbra but also with the core in each patient. There was a significant (p <=
      0.001) correlation in the expected direction between FMISO uptake and perfusion,
      with a sharp FMISO uptake bend around the expected penumbra threshold.
      CONCLUSION: FMISO uptake had the expected overlap with the penumbra and
      relationship with local perfusion. However, consistent with recent animal data,
      our study suggests FMISO trapping may not be specific to the penumbra. If
      confirmed in larger samples, this preliminary finding would have potential
      implications for the clinical application of FMISO PET in acute ischaemic stroke.

PMID- 24126470
TI  - Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in
      refractory psychosis.
AB  - Refractory psychosis units currently have little information regarding which
      symptoms profiles should be expected to respond to treatment. In the current
      study, we provide this information using structural equation modeling of Positive
      and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a
      sample of 610 patients admitted to a treatment refractory psychosis program at a
      Canadian tertiary care unit between 1990 and 2011. The hypothesized five
      dimensional structure of the PANSS fit the data well at both admission and
      discharge, and the latent variable scores are reported as a function of symptom
      dimension and diagnostic category. The results suggest that, overall, positive
      symptoms (POS) responded to treatment better than all other symptoms dimensions,
      but for the schizoaffective and bipolar groups, greater response on POS was
      observed relative to the schizophrenia and major depression groups. The major
      depression group showed the most improvement on negative symptoms and emotional
      distress, and the bipolar group showed the most improvement on disorganization.
      Schizophrenia was distinct from schizoaffective disorder in showing reduced
      treatment response on all symptom dimensions. These results can assist refractory
      psychosis units by providing information on how PANSS symptom dimensions respond
      to treatment and how this depends on diagnostic category. 

PMID- 24126471
TI  - All placebos are not created equally.

PMID- 24126473
TI  - Process evaluation of software using the international classification of external
      causes of injuries for collecting burn injury data at burn centers in the United
      States.
AB  - Detailed information on the cause of burns is necessary to construct effective
      prevention programs. The International Classification of External Causes of
      Injury (ICECI) is a data collection tool that allows comprehensive categorization
      of multiple facets of injury events. The objective of this study was to conduct a
      process evaluation of software designed to improve the ease of use of the ICECI
      so as to identify key additional variables useful for understanding the
      occurrence of burn injuries, and compare this software with existing data
      collection practices conducted for burn injuries. The authors completed a process
      evaluation of the implementation and ease of use of the software in six U.S. burn
      centers. They also collected preliminary burn injury data and compared them with
      existing variables reported to the American Burn Association's National Burn
      Repository (NBR). The authors accomplished their goals of 1) creating a data
      collection tool for the ICECI, which can be linked to existing operational
      programs of the NBR, 2) training registrars in the use of this tool, 3)
      establishing quality-control mechanisms for ensuring accuracy and reliability, 4)
      incorporating ICECI data entry into the weekly routine of the burn registrar, and
      5) demonstrating the quality differences between data collected using this tool
      and the NBR. Using this or similar tools with the ICECI structure or key selected
      variables can improve the quantity and quality of data on burn injuries in the
      United States and elsewhere and thus can be more useful in informing prevention
      strategies. 

PMID- 24126474
TI  - The true meshing ratio of skin graft meshers.
AB  - Skin meshing is frequently used in the coverage of extensive burn injuries as
      well as other skin and soft tissue wounds. This technique allows coverage of more
      extensive areas with smaller donor sites and prevents fluid from collecting
      beneath the skin grafts. The devices used to achieve this expansion differ in
      their technology and the use of skin carriers. In addition, many of the devices
      permit meshing at single or multiple ratios depending upon the device chosen.
      Although commonly used, there have been few definitive studies analyzing the
      actual expansion ratios achieved by many of these devices. The purpose of this
      study was to measure the actual meshing ratios achieved using some of the most
      commonly used skin meshers. The authors used split-thickness cadaveric skin
      samples provided by the regional tissue bank to compare the area of skin both
      before and after meshing to determine the actual expansion ratio and compared
      that with the ratio claimed by the device manufacturer. For all ratios greater
      than 1:1, the extent of actual expansion was significantly less than that
      expected for each device (P < .001). In addition, using devices that claimed to
      yield increasingly greater expansion ratios resulted in increasingly greater
      discrepancies between the area predicted by the device manufacturer and the
      actual surface area of skin (P < .01). These findings suggest that there is great
      variability in the expected and observed expansion ratios achieved by skin graft
      meshing devices. This has significant applicability to practice as it is likely
      to affect surgical decisions related to estimating the extent of donor area
      needed to cover skin and soft tissue defects. 

PMID- 24126475
TI  - [Monitoring of radiological interventions].

PMID- 24126476
TI  - Metabolism: Jet lag prevented in mutant mice.

PMID- 24126477
TI  - Obesity: Hsp60 integrates central crosstalk.

PMID- 24126478
TI  - Diabetes: Efficacy of dapagliflozin associated with renal function.

PMID- 24126479
TI  - Pain: Opioid use in patients undergoing bariatric surgery.

PMID- 24126480
TI  - Obesity: Can inflammatory status define metabolic health?
AB  - A recent study shows that inflammation could be the underlying factor that
      determines the differences in metabolic profiles between subgroups of obesity. An
      improved understanding and characterization of these subgroups should help to
      develop innovative approaches to treat obesity.

PMID- 24126482
TI  - Neuroendocrinology: Mitofusins and energy balance.

PMID- 24126483
TI  - Sulforaphane protects hearts from early injury after experimental
      transplantation.
AB  - BACKGROUND: Oxidative stress is a major factor in the development of ischemia
      reperfusion injury (IRI) after heart transplantation. The isothiocyanate found in
      broccoli - sulforaphane (SFN) - is an indirect antioxidant that acts by inducing
      Nrf2-dependent Phase 2 enzymes, such as NAD(P)H-quinone oxidoreductase 1,
      glutathione reductase, glutathione peroxidase, and the cardioprotective enzymes,
      haemoxygenase-1 (HO-1) and thioredoxin (Trx-1), participate in adaptive and
      protective responses to oxidative stress and various inflammatory stimuli. The
      aim of this study was to ameliorate IRI following heart transplants by recipient
      preconditioning. MATERIAL AND METHODS: Male Lewis rats were randomly divided into
      groups of n=10 animals each for heart donation. Heart grafts underwent 18 hours
      of cold storage in histidine-tryptophanketoglutarate (HTK) solution.
      Preconditioning of recipients with sulforaphane was performed 24 hours before
      transplantation. RESULTS: SFN significantly decreased serum levels of TnT, CK, CK
      MB, LDH, AST, and ALT, which correlated with better graft function scores and
      improved survival prognosis. Pretreated recipients showed significantly decreased
      expression of iNOS, caspase 3, and HIF-1a. CONCLUSIONS: Our results indicate that
      recipient preconditioning with SFN protects the heart from IRI after experimental
      transplantation.

PMID- 24126481
TI  - Diagnosis and management of Graves disease: a global overview.
AB  - Graves disease is an autoimmune disorder characterized by goitre, hyperthyroidism
      and, in 25% of patients, Graves ophthalmopathy. The hyperthyroidism is caused by
      thyroid hypertrophy and stimulation of function, resulting from interaction of
      anti-TSH-receptor antibodies (TRAb) with the TSH receptor on thyroid follicular
      cells. Measurements of serum levels of TRAb and thyroid ultrasonography represent
      the most important diagnostic tests for Graves disease. Management of the
      condition currently relies on antithyroid drugs, which mainly inhibit thyroid
      hormone synthesis, or ablative treatments ((131)I-radiotherapy or thyroidectomy)
      that remove or decrease thyroid tissue. None of these treatments targets the
      disease process, and patients with treated Graves disease consequently experience
      either a high rate of recurrence, if receiving antithyroid drugs, or lifelong
      hypothyroidism, after ablative therapy. Geographical differences in the use of
      these therapies exist, partially owing to the availability of skilled thyroid
      surgeons and suitable nuclear medicine units. Novel agents that might act on the
      disease process are currently under evaluation in preclinical or clinical
      studies, but evidence of their efficacy and safety is lacking. 

PMID- 24126484
TI  - Measurements with the new PHE neutron survey instrument.
AB  - A novel design of survey instrument has been developed to accurately estimate
      ambient dose equivalent from neutrons with energies in the range from thermal to
      20 MeV. The device features moderating and attenuating layers to ease measurement
      of fast and intermediate energy neutrons, combined with guides that channel low
      energy neutrons to the single, central detector. A prototype of this device has
      been constructed and exposed to a set of calibration fields: the resulting
      measured responses are presented and discussed here, and compared against Monte
      Carlo data. A simple simulated workplace neutron field has also been developed to
      test the device. 

PMID- 24126485
TI  - Photon doses in NPL standard neutron fields.
AB  - Standard neutron fields are invariably accompanied by a photon component due to
      the neutron-generating reactions and secondary neutron interactions in the
      surrounding environment. A set of energy-compensated Geiger-Muller (GM) tubes and
      electronic personal dosemeters (EPDs) have been used to measure the photon dose
      rates in a number of standard radionuclide and accelerator-based neutron fields.
      The GM tubes were first characterised in standard radioisotope and X-ray photon
      fields and then modelled using MCNP to determine their photon dose response as a
      function of energy. Values for the photon-to-neutron dose equivalent ratios are
      presented and compared with other published values. 

PMID- 24126486
TI  - Measurement of neutron ambient dose equivalent in carbon-ion radiotherapy with an
      active scanned delivery system.
AB  - In ion beam radiotherapy, secondary neutrons contribute to an undesired dose
      outside the target volume, and consequently the increase of secondary cancer risk
      is a growing concern. In this study, neutron ambient dose equivalents in carbon
      ion radiotherapy (CIRT) with an active beam delivery system were measured with a
      rem meter, WENDI-II, at National Institute of Radiological Sciences. When the
      same irradiation target was assumed, the measured neutron dose with an active
      beam was at most ~15 % of that with a passive beam. This percentage became
      smaller as larger distances from the iso-centre. Also, when using an active beam
      delivery system, the neutron dose per treatment dose in CIRT was comparable with
      that in proton radiotherapy. Finally, it was experimentally demonstrated that the
      use of an active scanned beam in CIRT can greatly reduce the secondary neutron
      dose. 

PMID- 24126487
TI  - Bonner sphere measurements of 241Am-B and 241Am-F neutron energy spectra unfolded
      using high-resolution a priori data.
AB  - High-resolution neutron energy spectra, covering the entire energy range of
      interest, for two standard radionuclide neutron sources ((241)Am-B and (241)Am-F)
      have been derived from Bonner sphere measurements by using high-resolution a
      priori data in the unfolding process. In each case, two a priori spectra were
      used, one from a two-stage calculation and also one from a combination of the
      calculated spectrum with a high-resolution measured spectrum. The unfolded
      spectra are compared with those published elsewhere and show significant
      differences from the ISO- and IAEA-recommended spectra for (241)Am-B and (241)Am
      F, respectively. Values for the fluence-average energy and fluence-to-dose
      equivalent conversion coefficients are presented for the new spectra, and the
      implications of the new spectra for the emission rates of the sources when
      measured by the manganese bath technique are also determined. 

PMID- 24126489
TI  - Review: evidence-based psychotherapies are more effective than usual care for
      young people with psychopathology: effects are influenced by location of care and
      participant characteristics.

PMID- 24126488
TI  - Review: psychotherapy, somatic therapy and pharmacotherapy are all more effective
      than control for the treatment of PTSD.

PMID- 24126490
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans formed from sucralose at high
      temperatures.
AB  - Sucralose is a widely-used artificial high-intensity sweetener. Although doubts
      have been raised about the safety of sucralose by several researchers, it can
      still be found in a broad range of foods and beverages worldwide, including in
      baked goods. Sucralose may decompose at high temperatures, and participate in
      chlorination reactions, generating highly toxic compounds. Here, we demonstrate
      that heating sucralose at high temperatures in stainless steel or other metal
      utensils in the presence of rust (Al2O3, Fe2O3, and CuO) produces polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). PCDD/Fs were found in smoke
      generated during the heating of sucralose and in the residues after heating. CuO
      enhanced the PCDD/F yield in comparison with Al2O3 and Fe2O3. 

PMID- 24126491
TI  - Cytotoxicity of Vitex agnus-castus fruit extract and its major component,
      casticin, correlates with differentiation status in leukemia cell lines.
AB  - We have demonstrated that an extract from the ripe fruit of Vitex agnus-castus
      (Vitex) exhibits cytotoxic activities against various types of solid tumor cells,
      whereas its effects on leukemia cells has not been evaluated to date. In this
      study, the effects of Vitex and its major component, casticin, on leukemia cell
      lines, HL-60 and U-937, were investigated by focusing on proliferation, induction
      of apoptosis and differentiation. Identification and quantitation by NMR
      spectroscopy showed that casticin accounted for approximate 1% weight of Vitex.
      Dose-dependent cytotoxicity of Vitex and casticin was observed in both cell
      lines, and HL-60 cells were more sensitive to the cytotoxicity of Vitex/casticin
      compared to U-937 cells. Furthermore, compared to unstimulated HL-60 cells,
      phorbol 12-myristate 13-acetate (PMA)- and 1,25-dihydroxyvitamin D3 (VD3)
      differentiated HL-60 cells acquired resistance to Vitex/casticin based on the
      results from cell viability and apoptosis induction analysis. Since the HL-60
      cell line is more immature than the U-937 cell line, these results suggested that
      the levels of cytotoxicity of Vitex/casticin were largely attributed to the
      degree of differentiation of leukemia cells; that is, cell lines with less
      differentiated phenotype were more susceptible than the differentiated ones. RT
      PCR analysis demonstrated that PMA upregulated the expression of intercellular
      adhesion molecule-1 (ICAM-1) in HL-60 cells, and that anti-ICAM-1 monoclonal
      antibody not only abrogated PMA-induced aggregation and adhesion of the cells but
      also restored its sensitivity to Vitex. These results suggested that ICAM-1 plays
      a crucial role in the acquired resistance in PMA-differentiated HL-60 cells by
      contributing to cell adhesion. These findings provide fundamental insights into
      the clinical application of Vitex/casticin for hematopoietic malignancy.

PMID- 24126492
TI  - Toward mobile 3D visualization for structural biologists.
AB  - Technological advances in crystallography have led to the ever-rapidly increasing
      number of biomolecular structures deposited in public repertoires. This
      undoubtedly shifts the bottleneck of structural biology research from obtaining
      high-quality structures to data analysis and interpretation. The recently
      available glasses-free autostereoscopic laptop offers an unprecedented
      opportunity to visualize and study 3D structures using a much more affordable,
      and for the first time, portable device. Together with a gamepad re-programmed
      for 3D structure controlling, we describe how the gaming technologies can deliver
      the output 3D images for high-quality viewing, comparable to that of a passive
      stereoscopic system, and can give the user more control and flexibility than the
      conventional controlling setup using only a mouse and a keyboard. 

PMID- 24126493
TI  - kappa-carrageenan induces the disruption of intestinal epithelial Caco-2
      monolayers by promoting the interaction between intestinal epithelial cells and
      immune cells.
AB  - kappa-carrageenan (kappa-CGN) is an important food additive that has been
      demonstrated to induce colitis in animal models. In the present study, the
      effects of kappa-CGN were assessed using an in vitro co-culture system that
      contained intestinal epithelial Caco-2 cells and activated macrophage-like THP-1
      cells. The results demonstrated that in single cultures of Caco-2 and THP-1 cells
      treated with kappa-CGN, the cytotoxicity and the secretion levels of IL-1beta, IL
      6 and TNF-alpha were low. In the co-culture system, however, kappa-CGN treatment
      resulted in apoptosis and reduced the transepithelial electrical resistance of
      the Caco-2 cell monolayers. The secretion levels of TNF-alpha, IL-1beta and IL-6
      from the two cell types were increased significantly by kappa-CGN treatment.
      Furthermore, pretreatment of the co-culture system with anti-TNF receptor 1
      antibody suppressed the kappa-CGN-induced apoptosis and attenuated the changes in
      the levels of IL-6 and IL-1beta in the Caco-2 monolayers. This study indicated
      that kappa-CGN-induced TNF-alpha secretion is the main contributor to cellular
      damage in Caco-2 monolayers exposed to kappa-CGN.

PMID- 24126495
TI  - Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and
      phytochrome signaling pathways in Arabidopsis.
AB  - Seedling development including hypocotyl elongation is a critical phase in the
      plant life cycle. Light regulation of hypocotyl elongation is primarily mediated
      through the blue light photoreceptor cryptochrome and red/far-red light
      photoreceptor phytochrome signaling pathways, comprising regulators including
      COP1, HY5, and phytochrome-interacting factors (PIFs). The novel phytohormones,
      strigolactones, also participate in regulating hypocotyl growth. However, how
      strigolactone coordinates with light and photoreceptors in the regulation of
      hypocotyl elongation is largely unclear. Here, we demonstrate that strigolactone
      inhibition of hypocotyl elongation is dependent on cryptochrome and phytochrome
      signaling pathways. The photoreceptor mutants cry1 cry2, phyA, and phyB are
      hyposensitive to strigolactone analog GR24 under the respective monochromatic
      light conditions, while cop1 and pif1 pif3 pif4 pif5 (pifq) quadruple mutants are
      hypersensitive to GR24 in darkness. Genetic studies indicate that the enhanced
      responsiveness of cop1 to GR24 is dependent on HY5 and MAX2, while that of pifq
      is independent of HY5. Further studies demonstrate that GR24 constitutively up
      regulates HY5 expression in the dark and light, whereas GR24-promoted HY5 protein
      accumulation is light- and cryptochrome and phytochrome photoreceptor-dependent.
      These results suggest that the light dependency of strigolactone regulation of
      hypocotyl elongation is likely mediated through MAX2-dependent promotion of HY5
      expression, light-dependent accumulation of HY5, and PIF-regulated components. 

PMID- 24126496
TI  - Effect of teenage motherhood on cognitive outcomes in children: a population
      based cohort study.
AB  - OBJECTIVE: To examine the association between teenage motherhood and cognitive
      development at 5 years. DESIGN: Data from Millennium Cohort Study, a prospective,
      nationally representative UK cohort of 18 818 infants born between 2000 and 2001.
      PARTICIPANTS: 12 021 (64%) mother-child pairs from white, English-speaking,
      singleton pregnancies were included. METHODS: Cognitive ability at 5 years was
      measured by the British Ability Scales II. Difference in mean cognitive scores
      across maternal age groups was estimated using linear regression, with adjustment
      for potential confounders and mediators. RESULTS: 617 (5%) children were born to
      mothers aged <=18 years. Our analysis revealed that children of teenage mothers
      had significantly lower cognitive scores compared with children of mothers aged
      25-34 years: difference in mean score for verbal ability -8.9 (-10.88 to -6.86,
      p<0.001); non-verbal ability -7.8 (-10.52 to -5.19, p<0.001); spatial ability 
      4.7 (-6.39 to -3.07, p<0.001), which is equivalent to an average delay of 11, 7
      and 4 months, respectively. After adjustment for perinatal and sociodemographic
      factors, the effect of young maternal age on non-verbal and spatial ability mean
      scores was attenuated. A difference persisted in the mean verbal ability scores 
      3.8 (-6.34 to -1.34, p=0.003), equivalent to an average delay of 5 months.
      CONCLUSIONS: Results suggest that the difference observed in the initial analyses
      for non-verbal and spatial skills are almost entirely explained by marked
      inequalities in sociodemographic circumstances and perinatal risk. However, there
      remains a significant adverse effect on verbal abilities in the children born to
      teenage mothers.

PMID- 24126497
TI  - Benefits of early intramedullary nailing in femoral metastases.
AB  - PURPOSE: Pathological fractures of the long bones are common complications of
      metastatic disease; however, the outcome of different surgical techniques for the
      treatment of these fractures has not been clearly defined. The aim of this study
      was to evaluate differences in prophylactic and therapeutic intramedullary
      nailing in femoral metastasic implants. METHODS: Sixty-five patients with
      metastasis of the femur were analysed retrospectively (37 females; 28 males)
      between 1995 and 2011 (follow-up 15 months). Forty-four presented with
      pathological fractures and 21 impending fractures (Mirel >=7). The operative
      treatments used were intramedullary fixation with reamed long Gamma nails. The
      studied parameters were survival, radiological and analytical findings, and
      functional outcomes. RESULTS: Prophylactic nailing resulted in immediate
      postoperative deaths in 5% vs. 11.4% in therapeutic, and one technical
      complication was detected in each group. Among the surviving patients 75.9% of
      the fractures and 100 % of impending lesions were able to walk after the
      operation. The mean survival time was 11 months in the therapeutic (range 1-49)
      and 14 in the prophylactic group (1-34). The prophylactic intramedullary nails
      required a lower transfusion rate (1.4 concentrates vs. 3.0), mobilised earlier
      (day 4.0 vs. 9.7) and needed a shorter hospital stay (eight days vs. 16 days)
      compared to therapeutic nails (p < 0.05). CONCLUSION: Femoral intramedullary
      nailing of metastasic lesions provides satisfactory results both clinically and
      radiologically. Early treatment of the metastases prevents fractures and gives
      better results, improving life quality of these patients.

PMID- 24126498
TI  - Improved kinematics of total knee replacement following partially navigated
      modified gap-balancing technique.
AB  - PURPOSE: Navigation-based total knee arthroplasty (TKA) has proven its value for
      restoration of the limb axis. However, patient-orientated results after TKA show
      a wide variation from the correct implantation technique. Nonphysiological
      kinematics without posterior femoral rollback and tibial internal rotation in
      flexion could be one reason for this. We postulated that a modified gap-balancing
      technique with navigation of the tibia alone, in comparison to a conventional
      navigated technique, would: (1) obtain lateral femoral rollback, (2) alter
      condylar liftoff without midflexion instability, (3) significantly differ in
      femoral and tibial cuts, (4) not be inferior in leg-axis restoration and (5) be
      comparable in clinical short-term scores. METHODS: In this prospective study, we
      compared in vivo navigation-based kinematics pre- and postoperatively of 40
      consecutive TKA comprising 21 conventional navigation-based TKA and 19 TKA with
      the modified gap-balancing technique and a reduced navigation workflow. All cuts
      were double checked and compared with cuts proposed by the navigation system.
      Clinical results were assessed preoperatively and six months postoperatively.
      RESULTS: The modified gap-balancing technique resulted in significantly increased
      lateral femoral rollback (mean 16.3 mm) and lateral condylar liftoff (mean 1.3
      mm) compared to the conventional group. The modified technique comprised an
      average of 2.1 mm less distal femoral resection and an average of 4 degrees  less
      external rotation and 3.5 degrees  more flexion of the femoral component compared
      with the control group. Average tibial resection height was 1.1 mm greater and
      average tibial slope was 0.5 degrees  elevated compared to the control group. A
      neutral leg axis was achieved in all cases. Results showed no significant
      differences in clinical scores between groups. CONCLUSION: A partial navigation
      solely of the tibial cut can securely restore the leg axis. Modification of the
      surgical technique can possibly reproduce more physiological knee kinematics with
      higher lateral femoral rollback in flexion without midflexion instability. This
      might help reduce postoperative problems with the new implant and thus reduce the
      amount of unsatisfactory results. Despite equal short-term results, mid- to long
      term results are needed to prove whether or not this correlates with better
      clinical results and at least equal implant longevity.

PMID- 24126499
TI  - Ponseti method for late presentation of clubfoot.

PMID- 24126502
TI  - [Update on first-line and relapse chemotherapy for testicular cancer].
AB  - Germ-cell cancer (GCC) is still the most common cancer diagnosis in men between
      the ages of 20 and 45 years with an increasing incidence. Due to effective and
      standardized algorithms that have been developed to stratify patients into
      different risk groups, remarkable progress has been made in the medical treatment
      of testicular cancer with an overall cure rate of 88%. The application of
      surgery, radiotherapy and chemotherapy, the choice of chemotherapy agents as well
      as treatment duration is defined in international consensus guidelines. The
      guidelines are based on histology, tumor stages and presence or absence of
      already known and well-established risk factors. These stringent parameters
      guarantee the optimal curative treatment options for each GCC patient and can
      avoid overtreatment as well as undertreatment. For patients with early stage
      disease, careful consideration between possible side effects due to an adjuvant
      therapy and the expected relapse rate must be made, whereas in advanced tumor
      stages the optimal sequence of chemotherapy, surgery and radiotherapy is the
      focus. In patients who progress or relapse after first-line therapy, the issue of
      optimal treatment represents a particular challenge and is far more complex. It
      needs to take into account the analysis of special prognostic variables for a
      further risk-tailored therapy. A careful weighting between the chosen regimen and
      the often higher rate of treatment failure in contrast to increased toxic side
      effects is mandatory.The disregard of accurate risk stratification and
      application of accepted treatment standards for patients with GCC at the time of
      initial diagnosis or at relapse is associated with developing more extensive
      disease and more intensive treatment. It also results in lower cure rates with
      the need for further therapy or leads to death of the patient without ever having
      had a chance for cure.

PMID- 24126501
TI  - Couples, pairs, and clusters: mechanisms and implications of centromere
      associations in meiosis.
AB  - Observations of a wide range of organisms show that the centromeres form
      associations of pairs or small groups at different stages of meiotic prophase.
      Little is known about the functions or mechanisms of these associations, but in
      many cases, synaptonemal complex elements seem to play a fundamental role. Two
      main associations are observed: homology-independent associations very early in
      the meiotic program-sometimes referred to as centromere coupling-and a later
      association of homologous centromeres, referred to as centromere pairing or
      tethering. The later centromere pairing initiates during synaptonemal complex
      assembly, then persists after the dissolution of the synaptonemal complex. While
      the function of the homology-independent centromere coupling remains a mystery,
      centromere pairing appears to have a direct impact on the chromosome segregation
      fidelity of achiasmatic chromosomes. Recent work in yeast, Drosophila, and mice
      suggest that centromere pairing is a previously unappreciated, general meiotic
      feature that may promote meiotic segregation fidelity of the exchange and non
      exchange chromosomes. 

PMID- 24126503
TI  - [Neoadjuvant, adjuvant and palliative chemotherapy of penile cancer].
AB  - Data on the treatment of advanced penile carcinoma especially for chemotherapy
      are very limited. Due to the results of recent studies there has been a shift to
      taxan/cisplatinum based regimens. Initial case reports also showed a response to
      targeted therapy especially antibodies against epidermal growth factor receptor
      (EGFR). Nevertheless, a curative treatment by medicinal approaches alone does not
      appear to be possible for metastatic penile cancer and can be only cured by
      multimodal approaches, including neoadjuvant and adjuvant chemotherapy and
      salvage lymph node dissection. Palliative chemotherapy of advanced penile cancer
      has to be individually adapted and weighed against best supportive care for the
      final decision. 

PMID- 24126504
TI  - Meta-analysis of the prevalence, incidence and natural history of critical limb
      ischemia.
AB  - AIM: Critical limb ischemia (CLI) is a significant morbid condition among the
      elderly. The epidemiology and natural history of this condition are poorly
      defined. METHODS: Systematic review and meta-analysis of studies evaluating the
      prevalence, incidence and natural history of CLI were performed. RESULTS: Six
      studies reported on the prevalence of severe lower limb ischemia (ABI <0.60,
      ankle pressure <70 mmHg or Fontaine III-IV) in 82,923 subjects and its pooled
      prevalence was 800/100,000 population (95%CI 300-1400). The Oxford Vascular Study
      assessed the incidence of vascular events in the general population and estimated
      an incidence of CLI of 22/100,000 population per year (95%CI 17-28). Two studies
      reported an incidence of CLI in subjects >65 years old of 113 and 200/100,000
      population per year, respectively. Nine studies reported on the treatment
      strategy in 2144 legs with CLI: the pooled rate of any revascularization
      procedure was 70.4%, of primary amputation 8.4%, and of conservative treatment
      20.3%. After conservative treatment for CLI, one-year pooled leg salvage rate was
      57.4% (95%CI 45.1-69.7%, ten studies reporting on 734 legs included), survival
      75.4% (95%CI 59.2-91.6%, four studies included) and amputation-free survival
      51.4% (95%CI 32.7-71.2%, five studies included). CONCLUSION: The incidence of CLI
      in the elderly is rather high. Series reporting on treatment strategies in these
      patients showed that a revascularization is attempted in 70% of cases.
      Conservative treatment in patients with unreconstructable CLI, high operative
      risk and/or refusing any revascularization procedure is associated with
      acceptable one year leg salvage.

PMID- 24126505
TI  - Medical therapy for critical limb ischemia and the diabetic foot: an update.
AB  - Critical limb ischemia is the most severe manifestation of chronic peripheral
      artery disease (PAD). The goal of medical care is to provide symptomatic relief
      in patients who are unsuitable for percutaneous or surgical revascularization and
      to reduce systemic cardiovascular risk. PAD is a common manifestation of systemic
      atherosclerosis and is associated with significant morbidity and mortality. PAD
      represents a marker for premature cardiovascular events. Patients with PAD, even
      in the absence of a history of myocardial infarction or ischemic stroke, have
      approximately the same relative risk of death from cardiovascular causes as do
      patients with a history of coronary or cerebrovascular disease alone. The
      PARTNERS study demonstrated that patients with PAD were less likely to receive
      appropriate treatment for their atherosclerotic risk factors than those who were
      being treated for coronary artery disease. The long term prognosis of patients
      with PAD is significantly worse than for patients with coronary artery disease
      alone. Newer therapies are being investigated to treat patients with critical
      limb ischemia who are unsuitable candidates for revascularization, and these will
      be discussed briefly. 

PMID- 24126506
TI  - Endovascular first as "preliminary approach" for critical limb ischemia and
      diabetic foot.
AB  - The treatment of the critical limb ischemia (CLI) and diabetic foot (DB) is still
      object of discussion and the gold standard for revascularization has not yet been
      identified. In these two decades the introduction of endovascular procedures had
      a large impact on the surgical revascularization and were added to the practice
      of vascular surgeons in patients who cannot be candidates for a bypass. This may
      be due to significant comorbidities, a reduced life expectancy, infection or
      gangrene in the possible sites of distal anastomoses, the unavailability of
      suitable veins, or the absence of an adequate "landing zone" for the distal part
      of the bypass. Various studies have evaluated the role of PTA in DF and CLI that
      resulted favourable in terms of feasibility, technical efficacy, the reduced
      number of complications, and limb salvage rates. Anyway, long-term patency is
      better after bypass surgery than after angioplasty, which is burdened by a high
      restenosis rate. In our experience we tried to practice endovascular approach as
      a first choice. If the procedure cannot be concluded safely, we continue the
      intervention surgically or use a hybrid approach. The endovascular-first strategy
      seems to be the future regardless of comorbidity of the patient and the degree of
      pathology. The vascular surgeon remains the only specialist that can decide the
      correct intervention without pressure or been forced and, last but not least, the
      only one who can independently perform hybrid interventions. 

PMID- 24126507
TI  - Tips and tricks for a correct "endo approach".
AB  - The world is facing an epidemic of diabetes, consequently in the next years
      critical limb ischemia due to diabetic artery disease will become a major issue
      for vascular and endovascular operators. Revascularization is a key therapy in
      these patients because reestablishing an adequate blood supply to the wound is
      essential for healing avoiding a major amputation. In this paper, we summarize
      our experience in endovascular treatment of diabetic critical limb ischemia,
      focusing of the main technical challenges in treating below-the-knee vessels. We
      describe the following topics: 1) targets of the revascularization therapy:
      "complete" versus "partial" revascularization and the concept of wound related
      artery. Every procedure must be tailored on technically realistic strategies and
      on the general patient status; 2) the antegrade femoral access using both, the X
      ray and the ultrasound guided techniques; 3) the chronic total occlusions
      crossing strategy proposing a step-by-step approach: endoluminal, subintimal,
      retrograde approaches. Particular attention has been given to the different
      retrograde approaches: pedal-plantar loop technique, trans-collateral approaches
      and the different types of retrograde puncture. For each step we provide a
      complete description of the technical details and of the suitable devices.
      Eventually we in brief describe: 3) acute result optimization and 4) prevention
      of restenosis. 

PMID- 24126508
TI  - New devices for a better endovascular approach.
AB  - The endovascular approach has known a great evolution in terms of vessel patency
      and treatment possibilities. Longer and more complex lesions with a difficult
      anatomy can be addressed by a range of endovascular tools. However, to maintain
      the patency of the treated lesion is the true challenge. In order to fulfill
      these long-term expectations, newer devices have been developed. The drug-coated
      balloon combines local drug uptake with no residual material after treatment. To
      maintain patency and prevent recoil of the arterial wall, the drug-eluting stent
      has been created to offer stent support with an antiproliferative drug. The main
      drawbacks of the drug-coated balloon and the drug-eluting stent are being
      addressed by the drug-eluting absorbable scaffold. The initial scaffolding
      support in combination with the drug release during a prolonged period, poses the
      same advantages while the scaffold is being metabolized over time. This
      continuing evolution in endovascular tools paves the way to an endovascular
      treatment for the majority of peripheral artery diseases. 

PMID- 24126509
TI  - Open surgery for chronic limb ischemia: a review.
AB  - This review considers the role of the different revascularization strategies in
      patients with chronic limb ischemia (CLI) and reveals that clinical evidence
      guiding therapeutic decision-making in CLI is poor and only careful basic
      recommendations can be made. For diffuse aortoiliac disease with occlusion of the
      aorta, aortobifemoral bypass remains the best option if the patient is fit for
      open surgery. Unilateral iliac occlusion should be treated by primary stenting,
      but an iliofemoral bypass may be the best option when the disease extends down to
      the common and deep femoral arteries. For infrainguinal revascularisation, bypass
      using the saphenous vein remains the best option for patients with occlusion of
      the superficial femoral artery >25 cm and for patients with multiple occlusions
      of the infrapopliteal arteries. In the absence of leg veins, arm veins should be
      used. Prosthetic grafts are the last option. Endovascular techniques are
      recommended in patients with short arterial lesions and limited life expectancy
      <2 years. Finally some patients with CLI are best treated by primary amputation.
      In conclusion, this review demonstrates that neither an endo- first nor a bypass
      first attitude is appropriate in patients with CLI and suggests that these
      patients should be cared for by specialists in a multidisciplinary center in
      order to preserve their life and limbs, to conduct clinical trials and to control
      costs. 

PMID- 24126511
TI  - Management of ischemic diabetic foot.
AB  - Diabetic foot pathology represent the more disabling complication of diabetes.
      More the 1 million of diabetes patients undergo a lower limb amputation per year;
      85% of these amputation are preceded by un ulcer that can be avoided by a
      prevention program. Critical limb ischemia (CLI), the only independent cause of
      major amputation in diabetic population, can be correctly treated when an early
      diagnosis is made. Both endoluminal and surgical revascularization procedures can
      be applied in diabetes with high rate of success when performed by skilled
      operator. Infection of diabetic foot, in particular in patients suffering from
      peripheral artery disease (PVD), may rapidly evolves in severe local or systemic
      infection putting the patient at high risk of major amputation or death. Together
      with an early diagnosis of infection and ischemia it is mandatory to apply a
      correct medical and surgical treatment protocol with the aim to control infection
      and to improve blood perfusion to the foot. In case of infection surgical
      procedure should be applied first while revascularization procedure will follow
      soonest. Antibiotic therapy should be chosen considering different local
      biological pattern and different type of infection. Reconstructive surgery, the
      last step in treatment of any diabetic foot lesion, must obtain a functional
      residual foot or a stump that will allow the patient to go back walking soonest
      with residual good walking capacity. 

PMID- 24126510
TI  - The role of hybrid procedures in the treatment of critical limb ischemia.
AB  - Patients affected by critical limb ischemia (CLI) represent a complex and high
      risk clinical problem, and a multidisciplinary approach is often demanded. The
      amputation rate in patients affected by CLI is still high. Introduction of
      endovascular procedure shook up the CLI concept of treatment. The increasing
      experience of Vascular Surgeons in endovascular technique forced these specialist
      to match classic surgical skills and endovascular tools in order to achieve the
      best treatment for each patients. The combination of the two techniques
      identifies the hybrid procedure. Aim of this paper is to define indication,
      necessity and results of the hybrid procedure in patients suffering from CLI. 

PMID- 24126512
TI  - The diabetic foot: a review.
AB  - Diabetic foot ulceration (DFU) is among the most frequent complications of
      diabetes. Neuropathy and ischaemia are the initiating factors and infection is
      mostly a consequence. We have shown in this review that any DFU should be
      considered to have vascular impairment. DFU will generally heal if the toe
      pressure is >55 mmHg and a transcutaneous oxygen pressure (TcPO2) <30 mmHg has
      been considered to predict that a diabetic ulcer may not heal. The decision to
      intervene is complex and made according to the symptoms and clinical findings. If
      both an endovascular and a bypass procedure are possible with an equal outcome to
      be expected, endovascular treatments should be preferred. Primary and secondary
      mid-term patency rates are better after bypass, but there is no difference in
      limb salvage. Bedridden patients with poor life expectancy and a non
      revascularisable leg are indications for performing a major amputation. A deep
      infection is the immediate cause of amputation in 25% to 50% of diabetic
      patients. Patients with uncontrolled abscess, bone or joint involvement,
      gangrene, or necrotising fasciitis have a "foot-at risk" and need prompt surgical
      intervention with debridement and revascularisation. As demonstrated in this
      review, foot ulcer in diabetic is associated with high mortality and morbidity.
      Early referral, non-invasive vascular testing, imaging and intervention are
      crucial to improve DFU healing and to prevent amputation. Diabetics are eight to
      twenty-four times more likely than non-diabetics to have a lower limb amputation
      and it has been suggested that a large part of those amputations could be avoided
      by an early diagnosis and a multidisciplinary approach. 

PMID- 24126513
TI  - The multilayer flow modulator stent for the treatment of arterial aneurysms.
AB  - AIM: The purpose of this manuscript was to: 1) report our experience with the
      Multilayer Flow Modulator (MFM) for the treatment of peripheral, visceral and
      aortic aneurysms; 2) review the published literature regarding the outcomes of
      patients treated with the MFM; and 3) develop initial treatment guidelines
      regarding the MFM. METHODS: We reviewed our clinical experience with the MFM in
      58 high surgical risk patients. Thirty-one peripheral (PAAs), 9 visceral (VAAs)
      and 18 aortic aneurysms (10 thoracoabdominal [TAAA]; 8 abdominal) were treated.
      In addition, the PubMed database through April 2013, along with relevant websites
      and scientific presentations at international meetings, were quered regarding the
      MFM. Seventeen articles and 3 presentations were identified. Data regarding 178
      patients treated with the MFM were included for analysis including 57 PAAs, 31
      VAAs and 90 complex degenerative aortic lesions. Outcomes including technical
      success, 30-day mortality, endoleak rate and aneurysm-related survival were
      studied. RESULTS: In our experience, there were 47 males and the mean age was 62
      years (16-80). In patients with PAAs and VAAs, technical success with the MFM was
      100%. At 30 days, there were no deaths. Initial MFM patency was 97.5% (39/40)
      with patency of the thrombosed MFM successfully restored. Longer-term follow-up
      (mean 16 +/- 8 months) demonstrated progressive thrombosis and shrinkage of the
      aneurysm sacs and all side-branches were patent. In patients with aortic
      aneurysms, technical success was 100%, with no complications and no deaths at 30
      days. Longer-term follow-up (8 +/- 7 months) demonstrated aneurysm-related
      survival of 100%, all-cause survival of 83.3%, intervention-free survival of 100%
      and 100% patency of the side branches. The longest duration for aneurysm sac
      thrombosis was 18 months. A significant mean diameter reduction was observed at 6
      months (17.3 mm for the transversal maximal diameter and 13.83 mm for the antero
      posterior diameter) in the TAAA group. In the literature review, there was 100%
      technical success and a 97.7% 30-day survival rate in patients with PAAs and VAAs
      treated with the MFM. In follow-up (range 5-26 months), there were no aneurysm
      related deaths or aneurysm ruptures and the overall survival was 95.5%. Complete
      aneurysm exclusion was observed in 94.3% of the patients with significant
      aneurysm shrinkage in 83% of the patients. Nine (10%) MFMs occluded with most
      occlusions resulting from pre-existing conditions. Patency of 5 occluded MFMs
      were restored and 4 occluded MFMs were not treated and were asymptomatic. All
      covered side branches were patent except in a patient with thrombophilia who also
      had an occluded MFM. The treatment of complex aortic degenerative lesions with
      MFM demonstrates a 95.5% 30-day survival with 2 aneurysm ruptures for
      contrindicated use (previously ruptured aneurysm; mycotic aneurysm). Over the
      follow-up (range 3-28 months), all-cause survival was 87.8% and aneurysm-related
      survival was 96.7% (1 late rupture due to a type 1 endoleak). Side branches were
      patent for 97.7% of the treated cases and a 13.3% endoleak rate was reported.
      There were no neurological, renal or respiratory complications. Complete
      exclusion and size stability were achieved for most of the cases. CONCLUSION:
      Clinical experience with the MFM is increasing. The MFM has been used to treat
      many types of aneurysms including peripheral, visceral and aortic. Early results
      suggest that use of the MFM can help prevent aneurysm-related mortalities while
      maintining branch vessel patency. Additional study and investigation is needed.

PMID- 24126514
TI  - Current status of Hemobahn/Viabahn endografts for treatment of popliteal
      aneurysms.
AB  - The aim of the present study was to review the literature reporting the use of
      the Hemobahn/Viabahn endograft (W. L. Gore and Assoc Inc., Flagstaff, AZ, USA)
      for endovascular treatment of popliteal artery aneurysms (PAA). A PubMed database
      search was performed looking for studies reporting endovascular treatment of PAA
      with the Hemobahn/Viabahn endograft within the period January 2000-December 2012.
      All relevant studies were independently assessed and all references were examined
      for potentially missed relevant reports. Studies were included if they reported
      experience with five patients or more. Eight studies with 222 patients (mean age
      72.4 years, 92.3% male) and 251 PAA (mean diameter 2.9 mm, 14.3% symptomatic)
      were included. Thirteen cases (5.2%) were treated on an urgent basis, including
      three cases of ruptured PAA and 10 cases of acute limb ischemia. Initial
      technical success was 99.2%. The mean number of implanted endografts/PAA was 1.8
      (range 1-4). Thirty-day mortality was 1 (0.4%) patient. Perioperative
      complications occurred in 1.6%, consisting of three access site hematomas and one
      acute endograft thrombosis. Cumulative mean follow-up duration was 36.9 months.
      During this period, a total of 46 endograft failures (42 occlusions, 4 stenoses)
      were observed within a mean postoperative time interval of 10.8 months.
      Cumulative primary and secondary patency rates were 85.6% and 93.4% at one year,
      and 78.5% and 90.4% at 2 years, respectively. Limb salvage rate during follow-up
      was 99.2%. Endoleak was noticed in 15 (6%) cases and endograft migration in 13
      (5.2%) cases. Endograft fracture was reported in 14 (5.6%) cases, resulting in
      occlusion in six patients, and in type III and IV endoleaks in two patients.
      Secondary intervention during follow-up was required in 47 (18.7%) cases,
      including 32 reinterventions for endograft occlusion, four for endograft
      stenosis, and 11 for endoleak repair. Endovascular PAA repair with the
      Hemobahn/Viabahn endograft is feasible and safe yielding excellent initial
      technical success rates, minimum perioperative mortality and morbidity, and mid
      term patency and limb salvage rates comparable to open surgery. These results
      suggest that a significant proportion of patients might benefit from endovascular
      PAA repair. 

PMID- 24126515
TI  - Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of
      psychiatric disorders.
AB  - Structural brain abnormalities are central to schizophrenia (SZ), but it remains
      unknown whether they are linked to dysmaturational processes crossing diagnostic
      boundaries, aggravating across disease stages, and driving the neurodiagnostic
      signature of the illness. Therefore, we investigated whether patients with SZ (N
      = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N =
      57), and individuals in at-risk mental states for psychosis (ARMS; N = 89)
      deviated from the trajectory of normal brain maturation. This deviation was
      measured as difference between chronological and the neuroanatomical age (brain
      age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine
      learning system trained to individually estimate age from the structural magnetic
      resonance imagings of 800 healthy controls. Group-level analyses showed that
      BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and
      the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated
      with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second,
      BrainAGE increased across at-risk, recent onset, and recurrent states of SZ.
      Finally, BrainAGE predicted both patient status as well as negative and
      disorganized symptoms. These findings suggest that an individually quantifiable
      "accelerated aging" effect may particularly impact on the neuroanatomical
      signature of SZ but may extend also to other mental disorders. 

PMID- 24126516
TI  - Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection.
AB  - Porphyromonas gingivalis, a major periodontopathogen, is involved in the
      pathogenesis of periodontitis. Interleukin-1beta (IL-1beta), a proinflammatory
      cytokine, regulates innate immune responses and is critical for the host defense
      against bacterial infection. However, excessive IL-1beta is linked to periodontal
      destruction. IL-1beta synthesis, maturation, and secretion are tightly regulated
      by Toll-like receptor (TLR) signaling and inflammasome activation. We found much
      higher levels of inflammasome components in the gingival tissues from patients
      with chronic periodontitis than in those from healthy controls. To investigate
      the molecular mechanisms by which P. gingivalis infection causes IL-1beta
      secretion, we examined the characteristics of P. gingivalis-induced signaling in
      differentiated THP-1 cells. We found that P. gingivalis induces IL-1beta
      secretion and inflammatory cell death via caspase-1 activation. We also found
      that P. gingivalis-induced IL-1beta secretion and pyroptic cell death required
      both NLRP3 and AIM2 inflammasome activation. The activation of the NLRP3
      inflammasome was mediated by ATP release, the P2X7 receptor, and lysosomal
      damage. In addition, we found that the priming signal via TLR2 and TLR4
      activation precedes P. gingivalis-induced IL-1beta release. Our study provides
      novel insight into the innate immune response against P. gingivalis infection
      which could potentially be used for the prevention and therapy of periodontitis. 

PMID- 24126517
TI  - Insulin treatment modulates the host immune system to enhance Pseudomonas
      aeruginosa wound biofilms.
AB  - Diabetes affects 25.8 million people in the United States, or 8.3% of the
      population, and these numbers are even higher in developing countries. Diabetic
      patients are more susceptible to the development of chronic wounds with
      debilitating bacterial infections than nondiabetics. Previously, we compared the
      ability of the opportunistic pathogen Pseudomonas aeruginosa to cause biofilm
      associated infections in chronic wounds of diabetic and nondiabetic mice (C.
      Watters, K. DeLeon, U. Trivedi, J. A. Griswold, M. Lyte, K. J. Hampel, M. J.
      Wargo, and K. P. Rumbaugh, Med. Microbiol. Immunol. 202:131-141, 2013).
      Unexpectedly, we observed that insulin-treated diabetic mice had significantly
      more biofilm in their wounds, which correlated with higher antibiotic tolerance.
      Here, we investigated whether insulin treatment modulates the diabetic immune
      system to favor P. aeruginosa biofilm formation. Utilizing a murine chronic wound
      model, we found that DNA protected P. aeruginosa in the wounds of insulin-treated
      diabetic mice from antibiotic treatment. We also observed increased numbers of
      neutrophils, reduced numbers of macrophages, and increased cell death in the
      wounds of diabetic mice on insulin therapy. Taken together, these data suggest
      that high levels of lysed neutrophils in the wounds of diabetic mice on insulin,
      combined with fewer macrophages to remove the cellular debris, contribute to
      increased DNA levels, which enhance P. aeruginosa biofilms. 

PMID- 24126518
TI  - Brucella melitensis T cell epitope recognition in humans with brucellosis in
      Peru.
AB  - Brucella melitensis, one of the causative agents of human brucellosis, causes
      acute, chronic, and relapsing infection. While T cell immunity in brucellosis has
      been extensively studied in mice, no recognized human T cell epitopes that might
      provide new approaches to classifying and prognosticating B. melitensis infection
      have ever been delineated. Twenty-seven pools of 500 major histocompatibility
      complex class II (MHC-II) restricted peptides were created by computational
      prediction of promiscuous MHC-II CD4(+) T cell derived from the top 50 proteins
      recognized by IgG in human sera on a genome level B. melitensis protein
      microarray. Gamma interferon (IFN-gamma) and interleukin-5 (IL-5) enzyme-linked
      immunospot (ELISPOT) analyses were used to quantify and compare Th1 and Th2
      responses of leukapheresis-obtained peripheral blood mononuclear cells from
      Peruvian subjects cured after acute infection (n = 9) and from patients who
      relapsed (n = 5). Four peptide epitopes derived from 3 B. melitensis proteins
      (BMEI 1330, a DegP/HtrA protease; BMEII 0029, type IV secretion system component
      VirB5; and BMEII 0691, a predicted periplasmic binding protein of a peptide
      transport system) were found repeatedly to produce significant IFN-gamma ELISPOT
      responses in both acute-infection and relapsing patients; none of the peptides
      distinguished the patient groups. IL-5 responses against the panel of peptides
      were insignificant. These experiments are the first to systematically identify B.
      melitensis MHC-II-restricted CD4(+) T cell epitopes recognized by the human
      immune response, with the potential for new approaches to brucellosis diagnostics
      and understanding the immunopathogenesis related to this intracellular pathogen. 

PMID- 24126519
TI  - Secondary lymphoid organ homing phenotype of human myeloid dendritic cells
      disrupted by an intracellular oral pathogen.
AB  - Several intracellular pathogens, including a key etiological agent of chronic
      periodontitis, Porphyromonas gingivalis, infect blood myeloid dendritic cells
      (mDCs). This infection results in pathogen dissemination to distant inflammatory
      sites (i.e., pathogen trafficking). The alteration in chemokine-chemokine
      receptor expression that contributes to this pathogen trafficking function,
      particularly toward sites of neovascularization in humans, is unclear. To
      investigate this, we utilized human monocyte-derived DCs (MoDCs) and primary
      endothelial cells in vitro, combined with ex vivo-isolated blood mDCs and serum
      from chronic periodontitis subjects and healthy controls. Our results, using
      conditional fimbria mutants of P. gingivalis, show that P. gingivalis infection
      of MoDCs induces an angiogenic migratory profile. This profile is enhanced by
      expression of DC-SIGN on MoDCs and minor mfa-1 fimbriae on P. gingivalis and is
      evidenced by robust upregulation of CXCR4, but not secondary lymphoid organ (SLO)
      homing CCR7. This disruption of SLO-homing capacity in response to respective
      chemokines closely matches surface expression of CXCR4 and CCR7 and is consistent
      with directed MoDC migration through an endothelial monolayer. Ex vivo-isolated
      mDCs from the blood of chronic periodontitis subjects, but not healthy controls,
      expressed a similar migratory profile; moreover, sera from chronic periodontitis
      subjects expressed elevated levels of CXCL12. Overall, we conclude that P.
      gingivalis actively "commandeers" DCs by reprogramming the chemokine receptor
      profile, thus disrupting SLO homing, while driving migration toward inflammatory
      vascular sites. 

PMID- 24126521
TI  - New frontiers in type III secretion biology: the Chlamydia perspective.
AB  - Members of the order Chlamydiales comprise a group of exquisitely evolved
      parasites of eukaryotic hosts that extends from single-celled amoeba to mammals.
      The most notable are human pathogens and include the agent of oculogenital
      disease Chlamydia trachomatis, the respiratory pathogen C. pneumoniae, and the
      zoonotic agent C. psittaci. All of these species are obligate intracellular
      bacteria that develop within parasitophorous vesicles termed inclusions. This
      demanding lifestyle necessitates orchestrated entry into nonphagocytic cells,
      creation of a privileged intracellular niche, and subversion of potent host
      defenses. All chlamydial genomes contain the coding capacity for a nonflagellar
      type III secretion system, and this mechanism has arisen as an essential
      contributor to chlamydial virulence. The emergence of tractable approaches to the
      genetic manipulation of chlamydiae raises the possibility of explosive progress
      in understanding this important contributor to chlamydial pathogenesis. This
      minireview considers challenges and recent advances that have revealed how
      chlamydiae have maintained conserved aspects of T3S while exploiting
      diversification to yield a system that exerts a fundamental role in the unique
      biology of Chlamydia species. 

PMID- 24126522
TI  - Rapid nutritional remodeling of the host cell upon attachment of Legionella
      pneumophila.
AB  - Upon entry of Legionella pneumophila into amoebas and macrophages, host-mediated
      farnesylation of the AnkB effector enables its anchoring to the Legionella
      containing vacuole (LCV) membrane. On the LCV, AnkB triggers docking of K(48)
      linked polyubiquitinated proteins that are degraded by the host proteasomes to
      elevate cellular levels of amino acids needed for intracellular proliferation.
      Interference with AnkB function triggers L. pneumophila to exhibit a starvation
      response and differentiate into the nonreplicative phase in response to the basal
      levels of cellular amino acids that are not sufficient to power intracellular
      proliferation of L. pneumophila. Therefore, we have determined whether the
      biological function of AnkB is temporally and spatially triggered upon bacterial
      attachment to the host cell to circumvent a counterproductive bacterial
      differentiation into the nonreplicative phase upon bacterial entry. Here, we show
      that upon attachment of L. pneumophila to human monocyte-derived macrophages
      (hMDMs), the host farnesylation and ubiquitination machineries are recruited by
      the Dot/Icm system to the plasma membrane exclusively beneath sites of bacterial
      attachment. Transcription and injection of ankB is triggered by attached
      extracellular bacteria followed by rapid farnesylation and anchoring of AnkB to
      the cytosolic side of the plasma membrane beneath bacterial attachment, where
      K(48)-linked polyubiquitinated proteins are assembled and degraded by the
      proteasomes, leading to a rapid rise in the cellular levels of amino acids. Our
      data represent a novel strategy by an intracellular pathogen that triggers rapid
      nutritional remodeling of the host cell upon attachment to the plasma membrane,
      and as a result, a gratuitous surplus of cellular amino acids is generated to
      support proliferation of the incoming pathogen. 

PMID- 24126523
TI  - Protein antigens increase the protective efficacy of a capsule-based vaccine
      against Staphylococcus aureus in a rat model of osteomyelitis.
AB  - Staphylococcus aureus is an invasive bacterial pathogen, and antibiotic
      resistance has impeded adequate control of infections caused by this microbe.
      Moreover, efforts to prevent human infections with single-component S. aureus
      vaccines have failed. In this study, we evaluated the protective efficacy in rats
      of vaccines containing both S. aureus capsular polysaccharides (CPs) and
      proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus
      toxoid and administered to rats alone or together with domain A of clumping
      factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were
      delivered according to a preventive or a therapeutic regimen, and their
      protective efficacy was evaluated in a rat model of osteomyelitis. Addition of
      dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial
      load and bone morphological changes compared with immunization with either
      conjugate vaccine alone. Both the prophylactic and therapeutic regimens were
      protective. Immunization with dHla together with a pneumococcal conjugate vaccine
      used as a control did not reduce staphylococcal osteomyelitis. The emergence of
      unencapsulated or small-colony variants during infection was negligible and
      similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5
      or CP8 conjugate vaccine enhanced its efficacy against S. aureus osteomyelitis,
      indicating that the inclusion of multiple antigens will likely enhance the
      efficacy of vaccines against both chronic and acute forms of staphylococcal
      disease. 

PMID- 24126524
TI  - In vitro infection of bovine monocytes with Mycoplasma bovis delays apoptosis and
      suppresses production of gamma interferon and tumor necrosis factor alpha but not
      interleukin-10.
AB  - Mycoplasma bovis is one of the major causative pathogens of bovine respiratory
      complex disease (BRD), which is characterized by enzootic pneumonia, mastitis,
      pleuritis, and polyarthritis. M. bovis enters and colonizes bovine respiratory
      epithelial cells through inhalation of aerosol from contaminated air. The nature
      of the interaction between M. bovis and the bovine innate immune system is not
      well understood. We hypothesized that M. bovis invades blood monocytes and
      regulates cellular function to support its persistence and systemic
      dissemination. We used bovine-specific peptide kinome arrays to identify cellular
      signaling pathways that could be relevant to M. bovis-monocyte interactions in
      vitro. We validated these pathways using functional, protein, and gene expression
      assays. Here, we show that infection of bovine blood monocytes with M. bovis
      delays spontaneous or tumor necrosis factor alpha (TNF-alpha)/staurosporine
      driven apoptosis, activates the NF-kappaB p65 subunit, and inhibits caspase-9
      activity. We also report that M. bovis-infected bovine monocytes do not produce
      gamma interferon (IFN-gamma) and TNF-alpha, although the level of production of
      interleukin-10 (IL-10) is elevated. Our findings suggest that M. bovis takes over
      the cellular machinery of bovine monocytes to prolong bacterial survival and to
      possibly facilitate subsequent systemic distribution. 

PMID- 24126525
TI  - Ethanolamine and choline promote expression of putative and characterized
      fimbriae in enterohemorrhagic Escherichia coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important food-borne
      pathogen responsible for disease outbreaks worldwide. In order to colonize the
      human gastrointestinal (GI) tract and cause disease, EHEC must be able to sense
      the host environment and promote expression of virulence genes essential for
      adherence. Ethanolamine (EA) is an important metabolite for EHEC in the GI tract,
      and EA is also a signal that EHEC uses to activate virulence traits. Here, we
      report that EA influenced EHEC adherence to epithelial cells and fimbrial gene
      expression. Quantitative reverse transcriptase PCR indicated that EA promoted the
      transcription of the genes in characterized and putative fimbrial operons.
      Moreover, putative fimbrial structures were produced by EHEC cells grown with EA
      but not in medium lacking EA. Additionally, we defined two previously
      uncharacterized EA-regulated fimbrial operons, loc10 and loc11. We also tested
      whether choline or serine, both of which are also components of cell membranes,
      activated fimbrial gene expression. In addition to EA, choline activated fimbrial
      gene expression in EHEC. These findings describe for the first time the
      transcription of several putative fimbrial loci in EHEC. Importantly, the
      biologically relevant molecules EA and choline, which are abundant in the GI
      tract, promoted expression of these fimbriae. 

PMID- 24126526
TI  - Hexa-acylated lipid A is required for host inflammatory response to Neisseria
      gonorrhoeae in experimental gonorrhea.
AB  - Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted infection
      characterized by inflammation of the cervix or urethra. However, a significant
      subset of patients with N. gonorrhoeae remain asymptomatic, without evidence of
      localized inflammation. Inflammatory responses to N. gonorrhoeae are generated by
      host innate immune recognition of N. gonorrhoeae by several innate immune
      signaling pathways, including lipooligosaccharide (LOS) and other pathogen
      derived molecules through activation of innate immune signaling systems,
      including toll-like receptor 4 (TLR4) and the interleukin-1beta (IL-1beta)
      processing complex known as the inflammasome. The lipooligosaccharide of N.
      gonorrhoeae has a hexa-acylated lipid A. N. gonorrhoeae strains that carry an
      inactivated msbB (also known as lpxL1) gene produce a penta-acylated lipid A and
      exhibit reduced biofilm formation, survival in epithelial cells, and induction of
      epithelial cell inflammatory signaling. We now show that msbB-deficient N.
      gonorrhoeae induces less inflammatory signaling in human monocytic cell lines and
      murine macrophages than the parent organism. The penta-acylated LOS exhibits
      reduced toll-like receptor 4 signaling but does not affect N. gonorrhoeae
      mediated activation of the inflammasome. We demonstrate that N. gonorrhoeae msbB
      is dispensable for initiating and maintaining infection in a murine model of
      gonorrhea. Interestingly, infection with msbB-deficient N. gonorrhoeae is
      associated with less localized inflammation. Combined, these data suggest that
      TLR4-mediated recognition of N. gonorrhoeae LOS plays an important role in the
      pathogenesis of symptomatic gonorrhea infection and that alterations in lipid A
      biosynthesis may play a role in determining symptomatic and asymptomatic
      infections. 

PMID- 24126527
TI  - Bacterially expressed full-length recombinant Plasmodium falciparum RH5 protein
      binds erythrocytes and elicits potent strain-transcending parasite-neutralizing
      antibodies.
AB  - Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is
      an essential merozoite ligand that binds with its erythrocyte receptor, basigin.
      PfRH5 is an attractive malaria vaccine candidate, as it is expressed by a wide
      number of P. falciparum strains, cannot be genetically disrupted, and exhibits
      limited sequence polymorphisms. Viral vector-induced PfRH5 antibodies potently
      inhibited erythrocyte invasion. However, it has been a challenge to generate full
      length recombinant PfRH5 in a bacterial-cell-based expression system. In this
      study, we have produced full-length recombinant PfRH5 in Escherichia coli that
      exhibits specific erythrocyte binding similar to that of the native PfRH5
      parasite protein and also, importantly, elicits potent invasion-inhibitory
      antibodies against a number of P. falciparum strains. Antibasigin antibodies
      blocked the erythrocyte binding of both native and recombinant PfRH5, further
      confirming that they bind with basigin. We have thus successfully produced full
      length PfRH5 as a functionally active erythrocyte binding recombinant protein
      with a conformational integrity that mimics that of the native parasite protein
      and elicits potent strain-transcending parasite-neutralizing antibodies. P.
      falciparum has the capability to develop immune escape mechanisms, and thus,
      blood-stage malaria vaccines that target multiple antigens or pathways may prove
      to be highly efficacious. In this regard, antibody combinations targeting PfRH5
      and other key merozoite antigens produced potent additive inhibition against
      multiple worldwide P. falciparum strains. PfRH5 was immunogenic when immunized
      with other antigens, eliciting potent invasion-inhibitory antibody responses with
      no immune interference. Our results strongly support the development of PfRH5 as
      a component of a combination blood-stage malaria vaccine. 

PMID- 24126528
TI  - Yersinia enterocolitica inhibits Salmonella enterica serovar Typhimurium and
      Listeria monocytogenes cellular uptake.
AB  - Yersinia enterocolitica biovar 1B employs two type three secretion systems
      (T3SS), Ysa and Ysc, which inject effector proteins into macrophages to prevent
      phagocytosis. Conversely, Salmonella enterica serovar Typhimurium uses a T3SS
      encoded by Salmonella pathogenicity island 1 (SPI1) to actively invade cells that
      are normally nonphagocytic and a second T3SS encoded by SPI2 to survive within
      macrophages. Given the distinctly different outcomes that occur with regard to
      host cell uptake of S. Typhimurium and Y. enterocolitica, we investigated how
      each pathogen influences the internalization outcome of the other. Y.
      enterocolitica reduces S. Typhimurium invasion of HeLa and Caco-2 cells to a
      level similar to that observed using an S. Typhimurium SPI1 mutant alone.
      However, Y. enterocolitica had no effect on S. Typhimurium uptake by J774.1 or
      RAW264.7 macrophage-like cells. Y. enterocolitica was also able to inhibit the
      invasion of epithelial and macrophage-like cells by Listeria monocytogenes. Y.
      enterocolitica mutants lacking either the Ysa or Ysc T3SS were partially
      defective, while double mutants were completely defective, in blocking S.
      Typhimurium uptake by epithelial cells. S. Typhimurium encodes a LuxR homolog,
      SdiA, which detects N-acylhomoserine lactones (AHLs) produced by Y.
      enterocolitica and upregulates the expression of an invasin (Rck) and a putative
      T3SS effector (SrgE). Two different methods of constitutively activating the S.
      Typhimurium SdiA regulon failed to reverse the uptake blockade imposed by Y.
      enterocolitica. 

PMID- 24126529
TI  - Erythropoietin protects against murine cerebral malaria through actions on host
      cellular immunity.
AB  - Cerebral malaria (CM) is associated with excessive host proinflammatory responses
      and endothelial activation. The hematopoietic hormone erythropoietin (EPO)
      possesses neuroprotective functions in animal models of ischemic-hypoxic,
      traumatic, and inflammatory injuries. In the Plasmodium berghei ANKA model of
      experimental CM (ECM), recombinant human EPO (rhEPO) has shown evident protection
      against ECM. To elucidate the mechanism of EPO in this ECM model, we investigated
      the effect of rhEPO on host cellular immune responses. We demonstrated that
      improved survival of mice with ECM after rhEPO treatment was associated with
      reduced endothelial activation and improved integrity of the blood-brain barrier.
      Our results revealed that rhEPO downregulated the inflammatory responses by
      directly inhibiting the levels and functions of splenic dendritic cells.
      Conversely, rhEPO treatment led to significant expansion of regulatory T cells
      and increased expression of the receptor cytotoxic T lymphocyte antigen 4 (CTLA
      4). The data presented here provide evidence of the direct effect of rhEPO on
      host cellular immunity during ECM. 

PMID- 24126530
TI  - Cross-reactive immune responses as primary drivers of malaria chronicity.
AB  - The within-host dynamics of an infection with the malaria parasite Plasmodium
      falciparum are the result of a complex interplay between the host immune system
      and parasite. Continual variation of the P. falciparum erythrocyte membrane
      protein (PfEMP1) antigens displayed on the surface of infected red blood cells
      enables the parasite to evade the immune system and prolong infection. Despite
      the importance of antigenic variation in generating the dynamics of infection,
      our understanding of the mechanisms by which antigenic variation generates long
      term chronic infections is still limited. We developed a model to examine the
      role of cross-reactivity in generating infection dynamics that are comparable to
      those of experimental infections. The hybrid computational model we developed is
      attuned to the biology of malaria by mixing discrete replication events, which
      mimics the synchrony of parasite replication and invasion, with continuous
      interaction with the immune system. Using simulations, we evaluated the dynamics
      of a single malaria infection over time. We then examined three major mechanisms
      by which the dynamics of a malaria infection can be structured: cross-reactivity
      of the immune response to PfEMP1, differences in parasite clearance rates, and
      heterogeneity in the rate at which antigens switch. The results of our
      simulations demonstrate that cross-reactive immune responses play a primary role
      in generating the dynamics observed in experimentally untreated infections and in
      lengthening the period of infection. Importantly, we also find that it is the
      primary response to the initially expressed PfEMP1, or small subset thereof, that
      structures the cascading cross-immune dynamics and allows for elongation of the
      infection. 

PMID- 24126531
TI  - MBL2 variations and malaria susceptibility in Indian populations.
AB  - Human mannose-binding lectin (MBL) encoded by the MBL2 gene is a pattern
      recognition protein and has been associated with many infectious diseases,
      including malaria. We sought to investigate the contribution of functional MBL2
      gene variations to Plasmodium falciparum malaria in well-defined cases and in
      matched controls. We resequenced the 8.7 kb of the entire MBL2 gene in 434
      individuals clinically classified with malaria from regions of India where
      malaria is endemic. The study cohort included 176 patients with severe malaria,
      101 patients with mild malaria, and 157 ethnically matched asymptomatic
      individuals. In addition, 830 individuals from 32 socially, linguistically, and
      geographically diverse endogamous populations of India were investigated for the
      distribution of functional MBL2 variants. The MBL2 -221C (X) allelic variant is
      associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9,
      corrected P value [P(Corr)] = 0.0036; severe malaria OR = 1.6, P(Corr) = 0.02).
      The exon1 variants MBL2*B (severe malaria OR = 2.1, P(Corr) = 0.036; mild versus
      severe malaria OR = 2.5, P(Corr) = 0.039) and MBL2*C (mild versus severe malaria
      OR = 5.4, P(Corr) = 0.045) increased the odds of having malaria. The exon1
      MBL2*D/*B/*C variant increased the risk for severe malaria (OR = 3.4, P(Corr) =
      0.000045). The frequencies of low MBL haplotypes were significantly higher in
      severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%).
      The MBL2*LYPA haplotypes confer protection, whereas MBL2*LXPA increases the
      malaria risk. Our findings in Indian populations demonstrate that MBL2 functional
      variants are strongly associated with malaria and infection severity. 

PMID- 24126532
TI  - Hemoglobin receptor protein from Porphyromonas gingivalis induces interleukin-8
      production in human gingival epithelial cells through stimulation of the mitogen
      activated protein kinase and NF-kappaB signal transduction pathways.
AB  - Periodontitis is an inflammatory disease of polymicrobial origin affecting the
      tissues supporting the tooth. The oral anaerobic bacterium Porphyromonas
      gingivalis, which is implicated as an important pathogen for chronic
      periodontitis, triggers a series of host inflammatory responses that promote the
      destruction of periodontal tissues. Among the virulence factors of P. gingivalis,
      hemoglobin receptor protein (HbR) is a major protein found in culture
      supernatants. In this study, we investigated the roles of HbR in the production
      of inflammatory mediators. We found that HbR induced interleukin-8 (IL-8)
      production in the human gingival epithelial cell line Ca9-22. p38 mitogen
      activated protein kinase (MAPK) and extracellular signal-related kinase 1/2
      (Erk1/2) were activated in HbR-stimulated Ca9-22 cells. Inhibitors of p38 MAPK
      (SB203580) and Erk1/2 (PD98059) blocked HbR-induced IL-8 production.
      Additionally, HbR stimulated the translocation of NF-kappaB-p65 to the nucleus,
      consistent with enhancement of IL-8 expression by activation of the NF-kappaB
      pathway. In addition, small interfering RNA (siRNA) targeting activating
      transcription factor 2 (ATF-2) or cyclic AMP-response element-binding protein
      (CREB) inhibited HbR-induced IL-8 production. Moreover, pretreatment with
      SB203580 and PD98059 reduced HbR-induced phosphorylation of CREB and ATF-2,
      respectively. Combined pretreatment with an inhibitor of NF-kappaB (BAY11-7082)
      and SB203580 was more efficient in inhibiting the ability of HbR to induce IL-8
      production than pretreatment with either BAY11-7082 or SB203580 alone. Thus, in
      Ca9-22 cells, the direct activation of p38 MAPK and Erk1/2 by HbR caused the
      activation of the transcription factors ATF-2, CREB, and NF-kappaB, thus
      resulting in the induction of IL-8 production. 

PMID- 24126533
TI  - Differentiation of antigen-specific T cells with limited functional capacity
      during Mycobacterium tuberculosis infection.
AB  - Despite the generation of Mycobacterium tuberculosis-specific T cell immune
      responses during the course of infection, only 5 to 10% of exposed individuals
      develop active disease, while others develop a latent infection. This phenomenon
      suggests defective M. tuberculosis-specific immunity, which necessitates more
      careful characterization of M. tuberculosis-specific T cell responses. Here, we
      longitudinally analyzed the phenotypes and functions of M. tuberculosis-specific
      T cells. In contrast to the functional exhaustion of T cells observed after
      chronic infection, M. tuberculosis-specific CD8(+) T cells differentiated into
      either effector (CD127(lo) CD62L(lo)) or effector memory (CD127(hi) CD62L(lo))
      cells, but not central memory cells (CD127(hi) CD62L(hi)), with low programmed
      death 1 (PD-1) expression, even in the presence of high levels of bacteria.
      Additionally, M. tuberculosis-specific CD8(+) and CD4(+) T cells produced
      substantial levels of tumor necrosis factor alpha (TNF-alpha) and gamma
      interferon (IFN-gamma), but not interleukin 2 (IL-2), upon in vitro
      restimulation. Among M. tuberculosis-specific CD8(+) T cells, CD127(hi) effector
      memory cells displayed slower ongoing turnover but greater survival potential. In
      addition, these cells produced more IFN-gamma and TNF-alpha and displayed lytic
      activity upon antigen stimulation. However, the effector function of M.
      tuberculosis-specific CD8(+) CD127(hi) effector memory T cells was inferior to
      that of canonical CD8(+) CD127(hi) memory T cells generated after acute
      lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate
      that M. tuberculosis-specific T cells can differentiate into memory T cells
      during the course of M. tuberculosis infection independent of the bacterial
      burden but with limited functionality. These results provide a framework for
      further understanding the mechanisms of M. tuberculosis infection that can be
      used to develop more effective vaccines. 

PMID- 24126534
TI  - Do hospitals really reward glitz but not quality?

PMID- 24126535
TI  - Difference in the recurrence rate between right- and left-sided colon cancer: a
      17-year experience at a single institution.
AB  - PURPOSE: The prognostic differences between right- and left-sided colon cancer
      are controversial. This study aimed to clarify the clinical difference between
      right- and left-sided colon cancer. METHODS: We enrolled 820 patients with stage
      I/II/III colon cancer who underwent radical surgery with curative intent. We
      explored the impact of the tumor location on the postoperative disease-free
      survival (DFS) rate using the univariate and multivariate analyses. RESULTS:
      Right-sided disease occurred in 399 of the 820 patients. The mean follow-up
      period was 55.8 +/- 34.9 months. The pathological stage distribution was as
      follows: stage I 261 patients; stage II 283; and stage III 251. There were no
      significant differences in the five-year DFS of the overall populations (right
      88.6%; left 89.4%; P = 0.231). The subgroup analyses demonstrated that patients
      with stage I right-sided colon cancer had a significantly better 5-year DFS rate
      than did those with left-sided disease (100 vs. 95.2%, P = 0.034). There were no
      significant differences in the distributions of the first recurrent sites (P =
      0.559). CONCLUSIONS: The tumor location may contribute to postoperative tumor
      recurrence. However, these effects were inconsistent across tumor stages. Our
      results provide a better understanding of the prognostic disparity between tumor
      locations; this may improve patient consent and postoperative surveillance.

PMID- 24126536
TI  - Characterization of the small RNA transcriptome in plant-microbe
      (Brassica/Erwinia) interactions by high-throughput sequencing.
AB  - Non-coding, small RNAs (sRNAs) have been identified in a wide spectrum of
      organisms ranging from bacteria to humans; however, the role and mechanisms of
      these sRNA in plant immunity is largely unknown. To determine possible roles of
      sRNA in plant-pathogen interaction, we carried out a high-throughput sRNA
      sequencing of Brassica campestris using non-infected plants and plants infected
      with Erwinia carotovora. Consistent with our hypothesis that distinct classes of
      host sRNAs alerts their expression levels in response to infection, we found
      that: (1) host 28-nt sRNAs were strongly increased under pathogen infection; and
      (2) a group of host sRNAs homologous to the pathogen genome also accumulated at
      significantly higher level. Our data thus suggest several distinct classes of the
      host sRNAs may enhance their function by up-regulation of their
      expression/stability in response to bacterial pathogen challenges. 

PMID- 24126539
TI  - Silver nanoparticles: a novel radiation sensitizer for glioma?
AB  - Malignant gliomas are the most common primary intracranial tumors with a dismal
      prognosis. Previous investigations by our group demonstrated the radiosensitizing
      effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the
      present study was to evaluate the efficacy of intratumoral administration of
      AgNPs in combination with a single dose of ionizing radiation at clinically
      relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20
      MUg/10 MUl) were stereotactically administered on day 8 after tumor implantation.
      One day after AgNP injection, rats bearing glioma received 10 Gy radiation. The
      mean survival times were 100.5 and 98 days, the corresponding percent increase in
      life spans was 513.2% and 497.7%, and the cure rates were 41.7 and 38.5% at 200
      days for the 10 and 20 MUg AgNPs and radiation combination groups, respectively.
      In contrast, the mean survival times for irradiated controls, 10 and 20 MUg AgNPs
      alone, and untreated controls were 24.5, 16.1, 19.4, and 16.4 days, respectively.
      Furthermore, a cooperative antiproliferative and proapoptotic effect was obtained
      when gliomas were treated with AgNPs followed by radiotherapy. Our results showed
      the therapeutic efficacy of AgNPs in combination with radiotherapy without
      apparent systemic toxicity, suggesting the clinical potential of AgNPs in
      improving the outcome of malignant glioma radiotherapy. 

PMID- 24126537
TI  - Natural history of Huntington disease.
AB  - IMPORTANCE: Understanding the natural history of Huntington disease will inform
      patients and clinicians on the disease course and researchers on the design of
      clinical trials. OBJECTIVE: To determine the longitudinal change in clinical
      features among individuals with Huntington disease compared with controls.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective, longitudinal cohort study at 44
      research sites in Australia (n = 2), Canada (n =4), and the United States (n =
      38). Three hundred thirty-four individuals with clinically manifest Huntington
      disease who had at least 3 years of annually accrued longitudinal data and 142
      controls consisting of caregivers and spouses who had no genetic risk of
      Huntington disease. MAIN OUTCOMES AND MEASURES: Change in movement, cognition,
      behavior, and function as measured by the Unified Huntington's Disease Rating
      Scale, the Mini-Mental State Examination, and vital signs. RESULTS: Total motor
      score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by
      0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI,
      0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by
      the product of frequency and severity score on the Unified Huntington's Disease
      Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional
      capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with
      controls, baseline body mass index was lower in those with Huntington disease
      (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P
      < .001). CONCLUSIONS AND RELEVANCE: Over 3 years, the cardinal features of
      Huntington disease all declined in a monotonic manner. These data quantify the
      natural history of the disease and may inform the design of trials aimed at
      reducing its burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00313495.

PMID- 24126541
TI  - It is possible: quality measurement during serious illness.

PMID- 24126540
TI  - Hypoxia reduces CD138 expression and induces an immature and stem cell-like
      transcriptional program in myeloma cells.
AB  - Although CD138 expression is a hallmark of plasma cells and myeloma cells,
      reduced CD138 expression is occasionally found. However, the mechanisms
      underlying CD138 downregulation in myeloma cells remain unclear. Previous reports
      suggest that the bone marrow microenvironment may contribute to CD138
      downregulation. Among various factors in the tumor microenvironment, hypoxia is
      associated with tumor progression, poor clinical outcomes, dedifferentiation and
      the formation of cancer stem cell niches in solid tumors. Since recent findings
      showed that progression of multiple myeloma (MM) delivers hypoxia within the bone
      marrow, we hypothesized that CD138 expression may be regulated by hypoxia. In the
      present study, we examined whether the expression of CD138 and transcription
      factors occurred in myeloma cells under hypoxic conditions. MM cell lines (KMS
      12BM and RPMI 8226) were cultured under normoxic or hypoxic conditions for up to
      30 days. Changes in the phenotype and the expression of surface antigens and
      transcription factors were analyzed using flow cytometry, RT-PCR and western
      blotting. All-trans retinoic acid (ATRA) was used to examine the phenotypic
      changes under hypoxic conditions. The expression levels of CD138, CS1 and plasma
      cell-specific transcription factors decreased under hypoxic conditions, while
      those of CD20, CXCR4 and B cell-specific transcription factors increased compared
      with those under normoxic conditions. Stem cell-specific transcription factors
      were upregulated under hypoxic conditions, while no difference was observed in
      ALDH activity. The reduced CD138 expression under hypoxic conditions recovered
      when cells were treated with ATRA, even under hypoxic conditions, along with
      decreases in the expression of stem cell-specific transcription factor.
      Interestingly, ATRA treatment sensitized MM cells to bortezomib under hypoxia. We
      propose that hypoxia induces immature and stem cell-like transcription phenotypes
      in myeloma cells. Taken together with our previous observation that decreased
      CD138 expression is correlated with disease progression, the present data suggest
      that a hypoxic microenvironment affects the phenotype of MM cells, which may
      correlate with disease progression. 

PMID- 24126542
TI  - Expression of neuronal protein Kidins220/ARMS in the spleen and peripheral blood
      of mice following airway allergen challenge.
AB  - Nerve growth factor (NGF), combined with the high-affinity tyrosine kinase
      receptor A (TrkA), has been reported to be involved in the pathogenesis of
      asthma. Ankyrin-rich membrane spanning/transmembrane substrate of protein kinase
      D (ARMS/Kidins220), a TrkA-binding protein, modulates the NGF signaling pathway.
      The aim of the present study was to investigate the expression of Kidins220/ARMS
      and the effect NGF has on the protein in the spleen and peripheral blood,
      following airway allergen challenge in mice. BALB/c mice were sensitized and
      challenged with ovalbumin. The effects of NGF on Kidins220/ARMS in the spleen and
      peripheral blood of mice were assessed by administering anti-NGF antibody.
      Expression of ARMS, interleukin (IL)-1beta and IL-4 in the spleen and peripheral
      blood was observed by reverse transcription-polymerase chain reaction, western
      blot analysis and immunohistochemistry. Pathological changes in the bronchi and
      lung tissues were examined by hematoxylin and eosin staining. Results showed that
      Kidins220/ARMS, IL-1beta and IL-4 were overexpressed in the spleen and peripheral
      blood following allergen challenge, compared with the control mice. Moreover,
      following treatment with anti-NGF, the levels of Kidins220/ARMS, IL-1beta and IL
      4 in the mice were downregulated. Therefore, the results of the present study
      showed that Kidins220/ARMS is expressed in the spleen and peripheral blood of
      normal BALB/c mice and may participate in the immuno-inflammation of asthma
      through the NGF-mediated signaling pathway.

PMID- 24126543
TI  - Can genotype be used to tailor treatment of obesity? State of the art and
      guidelines for future studies and applications.
AB  - Current treatments for losing weight based mainly on diet and exercise are, in
      general, unsuccessful. So, as an alternative to the general strategy of one-size
      fits-all, a more individualized approach is proposed through the so-called
      Personalised Medicine in which genotype data are used to personalize treatment
      and to optimize the results. This paper examines the current situation of the
      evidence on the influence of the genotype in modulating the association between
      diet or exercise on obesity and weight-related measures. Most of these studies
      are observational studies, as there are far fewer experimental ones assessing
      short-term weight-loss or its long-term maintenance. Many more studies are
      therefore required for that purpose. Having reviewed the results of the studies
      undertaken to date, we can say that huge progress has been made in identifying
      polymorphisms in genes related with obesity and that there is a great consistency
      of the influence of the FTO gene on the same, while for other variants, there is
      less consistency. Moreover, the results on gene-diet and gene-physical activity
      interactions in determining obesity phenotypes are very heterogeneous, so an
      important recommendation is to standardize the methodology for undertaking these
      studies. Furthermore, an important lack of replication has been observed
      suggesting undetected higher-level interactions and/or experimental caveats.
      Therefore, the current evidence level of applying genotype data to obesity
      treatment is at its early stages. Nevertheless, future prospects are encouraging
      and to make this come true, several guidelines are proposed for carrying out new
      studies on applications in clinical practice. 

PMID- 24126544
TI  - Bariatric and metabolic surgery.
AB  - In the beginning of the 21st century obesity still represents health, social and
      economical threat for most of economically wealthy countries worldwide. Estimated
      direct costs for obesity and related comorbidities treatment exceed 5% of the
      total health care costs both in the US and in European Union. However, in
      addition there are obesity-related indirect costs linked to more frequent work
      sickness leave, higher unemployment rates and overall lower productivity of obese
      patients. Surgical treatment of obesity (bariatric surgery) is the most effective
      long-term treatment modality for those patients suffering from higher degrees of
      obesity. Bariatric surgery has not only positive effects on weight loss, but is
      also extremely effective in improving or resolving many of obesity-related
      comorbidities, which have evolved rapidly into the so-called metabolic surgery.
      T2DM may serve as excellent example of metabolic, obesity-related comorbidity
      which can be treated with bariatric-metabolic procedure even without direct
      relation to weight loss. In such cases bariatric surgery evolves into metabolic
      surgery. Thus metabolic operations (namely from the malabsorptive end) deeply
      influence hormonal secretion especially in the proximal part of small bowel,
      change parametres of entero-insular axis and have positive influence on insulin
      secretion, sensitivity and on the entire complex of glucose tolerance. Nowadays
      we can witness dramatic changes in perception of T2DM from bariatric surgeons,
      diabetologists, and many other medical specialists. T2DM has evolved from
      primarily medical disease into a condition where surgeons may play a more active
      role in the management of the diabetic patient. However, it has to be stressed
      that metabolic treatment of T2DM and other metabolic disorders need
      multidisciplinary approach and collaboration and that surgeon should play very
      important role as a multidisciplinary team member, however metabolic surgery
      should not yet be considered as stand-alone treatment modality. 

PMID- 24126545
TI  - Obesity drug therapy.
AB  - Obesity is a chronic disease, and it requires chronic therapy. Hypertension,
      dyslipidemia, diabetes and cardiovascular diseases are leading causes of
      mortality in the modern world. All of them are strongly linked to obesity. While
      treating obesity, those conditions are also managed. Obese patients should always
      be treated through lifestyle interventions, though the results of such
      interventions are modest. Pharmacotherapy is a second step in the treatment of
      obesity, approved only when weight loss targets were not reached through
      lifestyle intervention. During the history of antiobesity drugs, many of them
      were withdrawn because of their side effects. Various guidelines recommend
      prescribing drug therapy for obesity through consideration of the potential
      benefits and limitations. Orlistat deactivates intestinal lipase and inhibits
      intestinal fat lipolysis. It is actually the only drug on the European market
      approved for the treatment of obesity. Orlistat therapy reduces weight to a
      modest extent, but it reduces the incidence of diabetes beyond the result
      achieved with lifestyle changes. Recently, some effective antiobesity drugs like
      sibutramine and rimonabant have been removed from the market due to their side
      effects. The new combination of topimarate and fentermine is approved in the US
      but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity
      is still an unresolved question. 

PMID- 24126547
TI  - Cancer recurrence in papillary thyroid microcarcinoma: a multivariate analysis on
      231 patients with a 12-year follow-up.
AB  - AIM: Papillary thyroid microcarcinoma (PMC) is considered a common disease with a
      good prognosis and low rate of recurrence but the extension of initial surgical
      treatment and the need of completion thyroidectomy are still controversial. Aim
      of this study is the assessment of the prognostic factors that are predictive of
      cancer recurrence on a large controlled series of patients with a prolonged
      follow-up. METHODS: A total of 231 patients with PMC were followed up for a
      median period of 12 years (range 5-35 years). The patients included 54 males and
      177 females, with a mean age at the time of first diagnosis of 45.7+/-12.7 years.
      RESULTS: At presentation 158 patients had no metastases, whereas 73 had lymph
      node metastases and 1 had bone metastases. Surgery included 177 total
      thyroidectomies and 54 lobectomies. Eighty-four patients underwent lymph node
      dissection, and 131 patients were treated with radioiodine therapy. The disease
      recurred in 15 patients (6.5%): 5 cases of local recurrence, all of which in the
      contralateral lobe after lobectomy, 13 cases of lymph-node metastases, and 2
      cases of lung metastases. Multivariate analysis showed that two parameters were
      predictive for local recurrence: age <45 years (P=0.05; RR: 6.9; 95% CI: 1.59
      29.9) and evidence of lymph-node metastases at presentation (P=0.03; RR: 3.24;
      95% CI: 1.17-8.55) CONCLUSION: Total or near-total thyroidectomy seems to reduce
      the risk of local recurrences in non-incidental PMC. Prophylactic dissection of
      central compartment nodes in the absence of clinically evident metastases seems
      not to change the risk of recurrence. In incidental PTMC without multifocality,
      extracapsular extension or histologically-proven lymph node metastases, lobectomy
      is associated with a very low risk of recurrence. Follow-up with neck
      ultrasonography seems advisable at yearly intervals, as recurrences may present
      from less than one year until several years after thyroidectomy. Radioiodine
      ablation of thyroid remnants should be considered only in young patients in
      presence of multifocal tumors, histologically-proven metastatic lymph nodes to
      the significantly higher risk of recurrence.

PMID- 24126548
TI  - Non-surgical management of thyroid abscess with ultrasound-guided fine-needle
      application of an antibiotic followed by sclerotization with absolute alcohol.
AB  - Thyroid abscess is a relatively rare yet dramatic condition of the thyroid gland
      requiring immediate therapeutic intervention. Traditionally, more or less
      aggressive surgical approaches and administration of broad-spectrum antibiotics
      have been used. Clinically less severe disease allows non-surgical treatment as
      well. The case report describes successful treatment of a large abscess of
      iatrogenic origin after biopsy of a cystic cavity. A combination of broad
      spectrum antibiotics was used based on culture results, administered both orally
      and by repeated application directly into the abscess cavity using an ultrasound
      guided fine-needle approach. Concurrent repeated evacuation of the cavity
      replaced drainage. Ultimately, a small residual cavity with sterile contents was
      managed by sclerotization with absolute alcohol. Clinical condition permitting,
      thyroid abscess may be successfully treated by repeated application of a targeted
      antibiotic, using a fine needle and ultrasound guidance, directly into the
      abscess cavity, with repeated evacuation replacing drainage. 

PMID- 24126546
TI  - Stress and eating behaviors.
AB  - Obesity is a heterogeneous construct that, despite multiple and diverse attempts,
      has been difficult to treat. One conceptualization gaining media and research
      attention in recent years is that foods, particularly hyperpalatable (e.g., high
      fat, high sugar) ones, may possess addictive qualities. Stress is an important
      factor in the development of addiction and in addiction relapse, and may
      contribute to an increased risk for obesity and other metabolic diseases.
      Uncontrollable stress changes eating patterns and the salience and consumption of
      hyperpalatable foods; over time, this could lead to changes in allostatic load
      and trigger neurobiological adaptations that promote increasingly compulsive
      behavior. This association may be mediated by alterations in the hypothalamic
      pituitary-adrenal (HPA) axis, glucose metabolism, insulin sensitivity, and other
      appetite-related hormones and hypothalamic neuropeptides. At a neurocircuitry
      level, chronic stress may affect the mesolimbic dopaminergic system and other
      brain regions involved in stress/motivation circuits. Together, these may
      synergistically potentiate reward sensitivity, food preference, and the wanting
      and seeking of hyperpalatable foods, as well as induce metabolic changes that
      promote weight and body fat mass. Individual differences in susceptibility to
      obesity and types of stressors may further moderate this process. Understanding
      the associations and interactions between stress, neurobiological adaptations,
      and obesity is important in the development of effective prevention and treatment
      strategies for obesity and related metabolic diseases. 

PMID- 24126549
TI  - A comparative study on the effects of type I and type II diabetes on learning and
      memory deficit and hippocampal neuronal loss in rat.
AB  - AIM: In addition to learning and memory impairments, diabetes may also brings
      about neuronal loss in different regions of the brain specially hippocampus. In
      this line, the present study was conducted to investigate the effects of type I
      (T1D) and type II (T2D) diabetes on cognitive function and hippocampal neuronal
      density in rat. METHODS: Three groups of male Wistar rats (N.=6) were regarded as
      control, T1D and T2D. T1D was induced by 60 mg/kg body weight of STZ injection
      and T2D by 10% fructose treatment through drinking water. Two months after the
      induction of both types of diabetes, learning abilities and memory retention of
      animals were measured using Morris Water Maze and shuttle box. All animals were
      perfused afterwards and their brains processed for stereological examination of
      hippocampal neuronal density. RESULTS: In parallel to significant decrease in
      learning and memory scores, T1D showed a meaningful reduction in hippocampal
      neuronal density, when compared to control group. In T2D, the reductions of
      cognitive scores as well as hippocampal neuronal density were not significant,
      when compared to control and T1D. CONCLUSION: Although both types of diabetes led
      to neuronal loss and spatial learning and memory dysfunction, these abnormalities
      were more obvious in T1D, while they are probably age-related and duration
      dependent in T2D.

PMID- 24126550
TI  - Cardiovascular risk factors, carotid artery intima media thickness, and HSCRP
      levels in patients with impaired glucose metabolism.
AB  - AIM: The aim of this paper was to compare serum high sensitivity C-reactive
      protein (HsCRP) levels and carotid artery intima-media thickness (CIMT) of
      patients with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
      with that in control subjects. METHODS: Ninety-six subjects with prediabetes, 48
      with IFG, of mean age 50.7+/-11.3 years, and 48 with IGT, of mean age 50.9+/-12.3
      years, were enrolled, along with 44 age-, sex-, and body mass index-matched
      controls with normal glucose tolerance. Serum HsCRP, lipid profile, insulin
      levels and the homeostasis model assessment of insulin resistance (HOMA-IR) was
      evaluated. High-resolution B-mode ultrasonography was performed. RESULTS: Serum
      HsCRP levels were significantly elevated in pre-diabetic patients when compared
      with that of control subjects. Median HsCRP values were 3.1 mg/L in IFG group,
      3.47 mg/L in IGT group, and 1.5 mg/L in the controls (P<0.001). CIMT was
      significantly higher in pre-diabetic groups than that in the control group (IFG:
      0.612+/-0.09; IGT: 0.625+/-0.1; control: 0.517+/-0.09, P<0.001). CIMT and HsCRP
      levels were similar in pre-diabetic groups. CIMT values were positively
      correlated with HsCRP (r=0.793, P=0.000), age (r=0.435, P=0.000), waist-hip ratio
      (r=0.170, P=0.044), fasting plasma glucose (r=0.302, P=0.000), HOMA-IR (r=0.173,
      P=0.041), and low-density lipoprotein cholesterol (r=0.168, P=0.047) levels.
      CONCLUSION: Both IFG and IGT were associated with increased cardiovascular risk
      as assessed by serum hsCRP levels and CIMT. In contrast to previous studies, risk
      appears to be the same in the two categories of prediabetes.

PMID- 24126551
TI  - Effects of physical exercise on the female reproductive system.
AB  - The excess in physical activity could be closely linked to considerable negative
      consequences on the whole body. These dysfunctions called as "female athlete
      triad"' by the American College of Sports Medicine (ACSM) include amenorrhea,
      osteoporosis and disorder eating. The female athlete triad poses serious health
      risks, both on the short and on the long term, to the overall well-being of
      affected individuals. Sustained low energy availability can impair health,
      causing many medical complications within skeletal, endocrine, cardiovascular,
      reproductive and central nervous system. On the contrary, several studies have
      shown, that physical activity improves cardiovascular risk factors, hormonal
      profile and reproductive function. These improvements include a decrease in
      abdominal fat, blood glucose, blood lipids and insulin resistance, as well as
      improvements in menstrual cyclicity, ovulation and fertility, decreases in
      testosterone levels and Free Androgen Index (FAI) and increases in sex hormone
      binding globulin (SHBG). Other studies reported that physical activity improved
      self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate
      the effect of physical exercise on female reproductive system and viceversa the
      impact of hormonal status on physical activity and metabolism. In addition this
      review supports the idea that physical exercise is a helpful tool for the
      management of obesity, prevention of cardiovascular, metabolic diseases and
      female reproductive organs related diseases (e.g. breast cancer). When the excess
      in physical activity leads up to the female athlete triad, it is imperative to
      treat each component of the triad by employing both pharmacological and non
      pharmacological treatments. 

PMID- 24126552
TI  - Fields of application of continuous subcutaneous insulin infusion in the
      treatment of diabetes and implications in the use of rapid-acting insulin
      analogues.
AB  - In western countries, diabetes mellitus, because of macrovascular and
      microvascular complications related to it, is still an important cause of death.
      Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of
      mortality than healthy patients. Since the Diabetes Control and Complications
      Trial (DCCT) established how an intensive therapy is necessary to prevent
      diabetes mellitus complications, many studies have been conducted to understand
      which method is able to reach an optimal metabolic control. In the past 30 years
      continuous subcutaneous insulin infusion established/introduced as a validate
      alternative to multiple daily injections. Several trials demonstrated that, when
      compared to MDI, CSII brings to a better metabolic control, in terms of a
      reduction of glycated hemoglobin and blood glucose variability, hypoglycemic
      episodes and improvement in quality of life. Because of their pharmacokinetic and
      pharmacodynamic characteristics, rapid-action insulin analogues are imposed as
      best insulin to be used in CSII. The rapid onset and the fast reached peak make
      them better mimic the way how pancreas secretes insulin. CSII by pump is not free
      from issues. Catheter occlusions, blockages, clogs can arrest insulin
      administration. The consequent higher levels of glycemic values, can easily bring
      to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a
      rapid analogue obtained by aminoacidic substitution. It is as effective as lispro
      and glulisine in gaining a good metabolic control and even better in reducing
      glucose variability. Some studies tried to compare rapid analogues in terms of
      stability. Obtained data are controversial. An in vivo study evidenced higher
      stability or glulisine, while studies in vitro highlighted a higher safety of
      aspart. Nowadays it is not possible to assess which analogues is safer. When the
      infusion set is changed every 48 hours equivalent rates of occlusions have been
      observed. 

PMID- 24126553
TI  - Polyendocrine syndrome type 3C in a family from Pakistan.
AB  - In type 3 polyendocrine syndrome (PAS3), autoimmune thyroiditis occurs with other
      organ-specific autoimmune disease, but not with autoimmune adrenalitis. In this
      report we described a family from Pakistan in which mother and three daughters
      were affected by a PAS3. We studied a family from Pakistan: Father MMu age 44,
      mother KN aged 44, three daughters MM age 20, MH age 16 and MA age 14 and a son
      MU age 18. These subjects were tested for thyroids function, metabolic function,
      adrenal function, autoimmune disease. In this family the four females were shown
      hypothyroidism with presence of anti thyroid autoantibodies (AA) and high TSH
      serum concentration in association with the presence of anti transglutaminase AA.
      Moreover KN, MM and MH were positive for anti nuclear AA (granular pattern) and
      for antibodies against Saccaromyces cerevisiae. MM was positive for AA against
      nuclear extractable antigens (SSA and SSB) too. No diabetes or pernicious anemia
      were observed. Adrenal and Pituitary function were normal. PAS 3C is an uncommon
      disease. In this family from Pakistan we observed a PAS3C in the four female
      members: mother and three daughters while father and son were unaffected.

PMID- 24126554
TI  - Evaluation of parathyroid levels and bone densitometry after cinacalcet treatment
      in severe primary hyperparathyroidism.

PMID- 24126555
TI  - Spontaneous chiral resolution directed by symmetry restriction and pi-pi
      interaction.
AB  - In order to understand and rationally construct homochiral self-assembled
      structures from racemic molecules, two novel crystalline metal-organic frameworks
      with chiral cavities were developed. The homochirality of the layers in both MOFs
      was achieved by forming strong coordinate bonds between the C3-symmetric
      cyclotriveratrylene and Zn4O(CO2)6 cluster. By changing weak pi-pi interactions
      between organic building blocks, the achiral assembly of ZnCTV-1 was successfully
      transformed into a chiral assembly in ZnCTV-2. This study demonstrated a possible
      route for designing the synthesis of chiral MOF through weak interactions. 

PMID- 24126556
TI  - The distribution of self-reported psychotic-like experiences in non-psychotic
      help-seeking mental health patients in the general population; a factor mixture
      analysis.
AB  - PURPOSE: Factor mixture analysis (FMA) and item response mixture models in the
      general population have shown that the psychosis phenotype has four classes. This
      study attempted to replicate this finding in help-seeking people accessing mental
      health services for symptoms of non-psychotic mental disorders. METHODS: All
      patients (18-35 years old) referred for non-psychotic mental health problems to
      the secondary mental healthcare service in The Hague between February 2008 to
      February 2010 (N = 3,694), were included. Patients completed the Prodromal
      Questionnaire (PQ). Hybrid latent class analysis was applied to explore the
      number, size and symptom profiles of the classes. RESULTS: The FMA resulted in
      four classes. Class 1 (N = 1,039, 28.1%) scored high on conceptual
      disorganization, inattention and mood disorder. Patients in Class 2 (N = 619,
      16.8%) endorsed almost all PQ-items, were more often screened as being psychotic
      or at high risk of developing psychosis, without care takers noticing. In Class 3
      (N = 1,747, 47.3%) perplexity, paranoia and negative symptoms were more
      prevalent. Patients were more often at high risk of developing psychosis. Class 4
      (N = 286, 7.7%) represented the 'normative' group with low probabilities for all
      items. DISCUSSION: The results support the hypothesis that a representation in
      four classes of psychotic-like experiences can also be applied in a help-seeking
      population.

PMID- 24126557
TI  - Gender differences in association between psychological distress and detailed
      living arrangements among Japanese older adults, aged 65-74 years.
AB  - PURPOSE: Past studies have shown that living alone is detrimental to older
      adults' mental health. However, there has been little focus on how older adults'
      psychological distress differed by more detailed living arrangement, as well as
      by gender. The present study investigates various living arrangements in
      association with psychological distress among older men and women. METHODS: Data
      from community-dwelling Japanese older adults were collected through a mail
      survey (n = 1,807, aged 65-74 years, 51.5 % men). Psychological distress level
      was measured using Kessler's six-item psychological distress scale. Living
      arrangements were categorized into four groups; "living with spouse only",
      "living with spouse and other family", "living with other family without spouse"
      or "living alone". Multiple logistic regression analyses were used to examine the
      associations of living arrangements with psychological distress level. RESULTS:
      Older adults living alone were observed to have higher psychological distress. In
      addition, gender-stratified analyses showed that higher distress levels were
      observed among older men living with family, but without a spouse (OR: 2.85, 95 %
      CI: 1.51-5.39). In contrast, higher distress was observed among older women
      living with spouse and other family (OR: 1.53, 95 % CI: 1.03-2.28). CONCLUSIONS:
      Psychological distress in older Japanese adults was associated with living
      arrangements, but such associations differed by gender. The association of living
      with a spouse on older men's mental health was striking, while living with any
      family was found to be rather important for older women, aged 65-74 years.

PMID- 24126558
TI  - "The psychological skeleton in the closet": mortality after a sibling's suicide.
AB  - PURPOSE: To study the association between loss of an adult sibling due to suicide
      and mortality from various causes up to 18 years after bereavement. METHODS: We
      conducted a follow-up study between 1981 and 2002, based on register data
      representing the total population of Swedes aged 25-64 years (n = 1,748,069).
      RESULTS: An elevated mortality rate from all causes was found among men (RR 1.26;
      95 % CI: 1.14-1.40) and women (1.27; 1.11-1.45) who had experienced a sibling's
      suicide. The standardized rate ratio of suicide of bereaved to non-bereaved
      persons was 2.46 (1.86-3.24) among men and 3.25 (2.28-4.65) among women. We also
      found some indications of an interrelation between sibling suicide and subsequent
      deaths from external causes other than suicide in men (1.77; 1.34-2.34) and
      deaths from cardiovascular disease in women (1.37; 0.99-1.91). An elevated all
      cause mortality rate was found after the first year of bereavement in men, while
      bereaved women experienced higher mortality rates during the first 2 years and
      after 5 years of bereavement. CONCLUSIONS: Our study provides support for adverse
      health effects among survivors associated with sibling loss due to suicide.
      Sibling suicides were primarily associated with suicide in bereaved survivors,
      although there was an increased mortality rate from discordant causes, which
      strengthens the possibility that the observed associations might not be entirely
      due to shared genetic causes.

PMID- 24126559
TI  - Gastric cancer: new biologic therapy effective as second-line treatment in
      gastric cancer.

PMID- 24126560
TI  - IBD: role of the pathologist in the diagnosis and management of IBD.

PMID- 24126561
TI  - Management of paediatric GERD.
AB  - Paediatric GERD is complicated to manage, as symptoms are diverse and often
      difficult to interpret. In infants, regurgitation is a common physiological
      condition. Nevertheless, when it occurs frequently (>4 times per day) and causes
      the infant distress, parents often seek medical help. In children 2-10 years of
      age, GERD is often considered to cause extra-oesophageal symptoms, despite the
      absence of hard evidence. Diagnostic investigations often lack solid validation
      and the signs and symptoms of GERD overlap with those of cow's milk protein
      allergy and eosinophillic oesophagitis. Reassurance, dietary treatment and
      positional adaptations are recommended for troublesome infant reflux. Anti-acid
      medication, mainly PPIs, is over-used in infants even though, in many children,
      reflux is not an acid-related condition. Moreover, evidence is increasing that
      PPIs cause adverse events such as gastroenteritis and respiratory tract
      infections. Management in children older than 10 years is similar to that in
      adults. Using prokinetics to treat nonerosive reflux disease remains only a
      promising theoretical concept, as no such molecule is currently available. Today,
      the adverse effects of each prokinetic molecule largely outweigh its potential
      benefit. Laparoscopic surgery is indicated in children who have life-threatening
      symptoms or in cases of drug dependence. 

PMID- 24126562
TI  - Transplantation: 3D printing of the liver in living donor liver transplantation.

PMID- 24126563
TI  - Small intestine: mucus-is it time to change your gut reaction?

PMID- 24126565
TI  - Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.
AB  - Xanthine oxidase is an important source of reactive oxygen species; so, it may
      play a role in the pathogenesis of endothelium dysfunction and its consequences.
      Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study
      aimed to investigate possible effects of allopurinol on nitroglycerin tolerance,
      vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic
      rings obtained from male Wistar rats, the effect of allopurinol was examined on
      nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by
      using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium
      nitroprusside, and nitroglycerin) were also measured and compared between tissues
      treated with and without allopurinol. All 3 concentrations of allopurinol (50,
      100, and 150 MUM) significantly acted against the development of nitroglycerin
      induced tolerance in comparison with controls. In terms of vasoconstriction and
      vasorelaxation, the effect of allopurinol was significant only on carbachol
      induced (endothelium related) vasorelaxation in a dose-dependent manner. In
      conclusion, although allopurinol had no significant effect on the contractile
      response of the aorta, in accord with the previous data, it significantly
      intensified endothelium-dependent vasodilation. The inhibitory effect of
      allopurinol against the development of nitrate-induced tolerance may suggest its
      clinical benefit and is worth to be studied more extensively.

PMID- 24126566
TI  - The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone on NF-kappaB and the
      inflammatory response during myocardial ischemia reperfusion injury in rats.
AB  - The aim of this study was to investigate the effect of 17-methoxyl-7-hydroxy
      benzene-furanchalcone (MHBFC) on nuclear factor-kappa-binding (NF-kappaB) and the
      inflammatory response in rats with myocardial ischemia reperfusion injury
      (MI/RI). Sprague-Dawley rats were randomly divided into 7 groups, and the rat
      MI/RI model was established by the ligation of the left anterior descending for
      30 minutes followed by ligation release for 1 hour. Areas of myocardial
      infarction were measured using Evans blue-2,3,5-Triphenyltetrazolium chloride
      (TTC) staining. Levels of malondialdehyde, glutathione peroxidase, and total
      superoxide dismutase were assessed. Release of interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), and interleukin-10 (IL-10) was measured by means of an
      enzyme-linked immunosorbent assay. NF-kappaBp65 and intercellular adhesion
      molecule-1 protein expression and caspase-3 and adenine nucleotide translocator-1
      messenger RNA expression were evaluated by immunohistochemistry and reverse
      transcription polymerase chain reaction, respectively. Pretreatment with MHBFC
      decreased the infarction areas, the malondialdehyde, IL-1beta and IL-6 levels,
      the expression of caspase-3, NF-kappaBp65, and intercellular adhesion molecule-1.
      Further, MHBFC increased total superoxide dismutase and glutathione peroxidase
      activities, the release of IL-10, and the expression of adenine nucleotide
      translocator-1 messenger RNA compared with the results of the model group. The
      experiment showed that MHBFC protected the heart against MI/RI possibly by
      reducing lipid peroxidation damage while inhibiting the activity of NF-kappaBp65
      and the inflammatory response.

PMID- 24126564
TI  - Pharmacological agents for NASH.
AB  - NASH is a common liver disease that increases liver-related mortality and reduces
      survival. The need for optimal management of NASH is therefore a priority for
      today's practicing hepatologist. The rationale for specific pharmacological
      therapy for NASH is based on the potential for disease progression and the
      difficulties that many patients have successfully implementing, in the long term,
      diet and lifestyle changes. Even in those that succeed, limited evidence exists
      that severe liver injury in patients with NASH can be reversed by diet and
      lifestyle measures alone. This Review provides a personal and critical assessment
      of the histological efficacy and safety of agents tested in randomized trials in
      patients with NASH. 

PMID- 24126567
TI  - Tolerability and pharmacokinetics of ACT-280778, a novel nondihydropyridine dual
      L/T-type calcium channel blocker: early clinical studies in healthy male subjects
      using adaptive designs.
AB  - ACT-280778 is a novel nondihydropyridine dual L/T-type calcium channel blocker.
      Two clinical studies (AC-067-101 and AC-067-102) were conducted to characterize
      its safety, tolerability, and pharmacokinetics in healthy male subjects after
      oral administration of single and multiple doses. Both trials were single-center,
      randomized, double-blind, placebo-controlled, adaptive design, ascending-dose
      studies, in which ACT-280778 was administrated as single doses of 2, 5, 15, or 40
      mg, or as once-daily doses of 5 or 15 mg for 7 days. Single and multiple doses up
      to and including 15 mg were well tolerated, and no serious or severe adverse
      event was reported in either study. A single dose of 40 mg was associated with
      abnormal electrocardiogram findings resulting in the discontinuation of further
      treatment at this dose or higher doses. ACT-280778 was rapidly absorbed, and
      larger than dose-proportional increases of the maximum plasma concentration and
      area under the plasma concentration-time curve were observed. Food intake delayed
      the time to maximum plasma concentration and doubled exposure. Urinary excretion
      of unchanged ACT-280778 was negligible, and accumulation at steady state was
      modest. Overall, pharmacokinetic and tolerability profiles of ACT-280778 observed
      in these 2 studies warranted further evaluation of ACT-280778 in a proof-of
      concept study in patients with hypertension.

PMID- 24126568
TI  - Perioperative levosimendan therapy is associated with a lower incidence of acute
      kidney injury after cardiac surgery: a meta-analysis.
AB  - OBJECTIVE: Levosimendan is a calcium sensitizer that enhances myocardial
      contractility without increasing myocardial oxygen use. Limited data are
      available on its renal-protective effect, and no statistically significant
      effects have been found. A meta-analysis was conducted for randomized studies to
      show whether perioperative levosimendan use could reduce acute kidney injury
      (AKI) in patients undergoing cardiac surgery. DATA SOURCES: BioMed Central,
      PubMed EMBASE, and the Cochrane Central Register of Controlled Trials were
      searched for pertinent studies. STUDY SELECTION: Randomized trials that compared
      levosimendan versus placebo or any other control in cardiac surgery with data on
      AKI were included. Exclusion criteria were duplicate publications, nonadult
      studies, oral administration of levosimendan, and studies with no data on AKI.
      DATA EXTRACTION: Study endpoints, study design, population, clinical setting,
      levosimendan dosage, and treatment duration were extracted. DATA SYNTHESIS: Data
      from 529 patients in 5 randomized trials were analyzed. The analysis showed that
      levosimendan decreased postoperative incidence of AKI in the levosimendan group.
      CONCLUSIONS: This analysis suggests that levosimendan might reduce renal injury
      in adult patients undergoing cardiac surgery. More prospective randomized studies
      are needed to further demonstrate the benefits of levosimendan on renal
      protection in cardiac surgery.

PMID- 24126569
TI  - Minimally invasive versus open surgery for acute Achilles tendon rupture: a
      systematic review.
AB  - INTRODUCTION: This review provides a comprehensive description of clinical,
      functional outcomes, and complications after open and minimally invasive surgery
      for Achilles tendon ruptures. SOURCES OF DATA: We systematically searched Medline
      (PubMED), EMBASE, CINHAL, Cochrane, Sports Discus and Google scholar databases
      using the combined keywords 'open repair', 'percutaneous surgery', 'minimally
      invasive surgery' 'Achilles tendon rupture', 'complications', 'infections',
      'wound disorders' to identify articles published in English, Spanish, French and
      Italian. AREAS OF AGREEMENT: Twelve studies fulfilled our inclusion criteria. Six
      studies were retrospective, five were randomized controlled trials and one was a
      prospective investigation. Of a total of 781 patients, 375 underwent open repair
      and 406 percutaneous surgery. Different procedures were performed for open and
      minimally invasive repair. AREAS OF CONTROVERSY: The range of motion was
      significantly greater after percutaneous repair than open surgery. The number of
      complications that occurred after open surgery was higher than after minimally
      invasive surgery. GROWING POINTS: Minimally invasive surgery is less expensive
      and less time demanding. AREAS TIMELY FOR DEVELOPING RESEARCH: Minimally invasive
      and open surgery of the Achilles tendon are grossly equivalent. However,
      iatrogenic neurological complications are more frequent after percutaneous
      repair. Novel percutaneous repairs have been proposed to minimize the risk of
      sural nerve injury.

PMID- 24126570
TI  - Cognitive emotion regulation strategies and neuroticism in relation to depressive
      symptoms following burn injury: a longitudinal study with a 2-year follow-up.
AB  - Sustaining burns is considered a stressful life event that has the power to
      elicit depressive symptoms. This study aimed to identify predictors of depressive
      symptoms by investigating the role of demographic variables, the number of
      operations (burn severity), neuroticism, and cognitive emotion regulation styles
      as possible influencing factors. Data from 242 patients with burns were analyzed
      employing latent growth modeling. The level of depressive symptoms across the 2
      year interval was associated with burn severity, higher levels of neuroticism and
      rumination, and lower levels of positive refocusing. Notably, rumination partly
      mediated the effect of neuroticism on the course of depressive symptoms.
      Correlational analysis suggested a specific effect of burn severity on
      rumination. The results indicate that screening for symptoms of depression,
      rumination, and neuroticism in burn patients is useful. Early interventions
      focusing on cognitive restructuring could assist in improving the cognitive
      emotional adaptation process following a burn event. 

PMID- 24126571
TI  - Impact of rituximab trials on the treatment of ANCA-associated vasculitis.
AB  - ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders
      characterized by a chronic relapsing course. Induction therapy is usually
      effective, but 70% of patients will relapse and 20% develop refractory disease.
      In the relapsing and refractory subgroups, treatment is complicated by the
      cumulative exposure to toxic drugs that contribute to poor long-term outcomes.
      The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the
      success of this targeted therapy has contributed to the evidence supporting a
      central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness
      originated from small, prospective trials and retrospective surveys conducted in
      AAV patients with relapsing and refractory disease; high remission rates
      permitted the reduction of glucocorticoids (GCS) doses and withdrawal of
      immunosuppressives. There has been controversy over the effectiveness of RTX in
      patients with predominantly granulomatous manifestations, where response rates
      have varied between studies, in part due to different RTX dosing regimens. These
      studies were followed by comparison of RTX against cyclophosphamide (CYC) for
      remission induction of new or relapsing AAV in two randomized trials, which led
      to the licensing of RTX for this indication. Subsequent attention has been turned
      to the use of RTX as a relapse prevention agent, to the potential for GCS sparing
      and to RTX-associated toxicity. We will discuss the impact that the results of
      RTX clinical trials have had on the management of AAV patients. 

PMID- 24126572
TI  - Integrating the management of Ruaha landscape of Tanzania with local needs and
      preferences.
AB  - Sustainable management of landscapes with multiple competing demands such as the
      Ruaha Landscape is complex due to the diverse preferences and needs of
      stakeholder groups involved. This study uses conjoint analysis to assess the
      preferences of representatives from three stakeholder groups-local communities,
      district government officials, and non-governmental organizations-toward
      potential solutions of conservation and development tradeoffs facing local
      communities in the Ruaha Landscape of Tanzania. Results demonstrate that there is
      little consensus among stakeholders about the best development strategies for the
      Ruaha region. This analysis suggests a need for incorporating issues deemed
      important by these various groups into a development strategy that aims to
      promote conservation of the Ruaha Landscape and improve the livelihood of local
      communities. 

PMID- 24126573
TI  - Motor cortical inhibition in ADHD: modulation of the transcranial magnetic
      stimulation-evoked N100 in a response control task.
AB  - The N100 component, evoked by transcranial magnetic stimulation (TMS) and
      electroencephalography is associated with the activation of inhibitory cortical
      circuits and has recently been suggested as a potential marker of inhibition in
      attention-deficit/hyperactivity disorder (ADHD). The aim of the present ADHD
      study was to investigate the modulation of the TMS-N100 in go and nogo trials of
      a response control task considering stages of response preparation, activation,
      execution and inhibition. Eighteen children with ADHD and 19 typically developing
      children, aged 10-14 years, were assessed. TMS was delivered over the left motor
      cortex, the TMS-N100 was measured at electrode P3. The TMS-N100 was determined at
      rest and at different time points (50 ms before S2; 150, 300 and 500 ms after S2)
      in a cued go/nogo task (S1-S2 paradigm). Correlations between the TMS-N100
      measures, MEP-related TMS measures (e.g., short-interval intracortical
      inhibition) and performance measures were calculated. At rest, the amplitude of
      TMS-N100 was not found to be significantly reduced in the ADHD group. During the
      go/nogo task, children with ADHD showed a smaller increase of TMS-N100 amplitude
      in go trials and a smaller decrease after inhibiting a response. In go trials, a
      lower TMS-N100 was associated with a smaller variability of reaction times. A
      smaller TMS-N100 modulation extends the picture of cortical inhibition deficits
      in ADHD. Findings suggest a functional involvement of the mechanisms underlying
      the TMS-N100 at the motor output stage.

PMID- 24126574
TI  - Age estimation of immature human skeletal remains from the diaphyseal length of
      the long bones in the postnatal period.
AB  - Age at death in immature human skeletal remains has been estimated from the
      diaphyseal length of the long bones, but few studies have actually been designed
      specifically for the purpose of age estimation and those which have, show
      important caveats. This study uses regression and classical calibration to model
      the relationship between age and diaphyseal length of the six long bones, in a
      sample of 184 known sex and age individuals (72 females and 112 males), younger
      than 13 years of age, selected from Portuguese and English skeletal collections.
      Age estimation models based on classical calibration were obtained for each of
      the six long bones, and separately for each sex and for the sexes combined, and
      also for the entire sample and when it is subdivided into two subsamples at the
      age of 2 years. Comparisons between inverse and classical calibration show there
      is a systematic bias in age estimations obtained from inverse calibration. In the
      classical calibration models, the length of the femur provides the most accurate
      estimates of age. Age estimates are more accurate for the male subsample and for
      individuals under the age of 2 years. These results and a test of previously
      published methods caution against inverse calibration as a technique for
      developing age estimation methods even from the immature skeleton. Age estimation
      methods developed using cemetery collections of identified human skeletons should
      not be uncritically applied to present-day populations from the same region since
      many populations have experienced dramatic secular trends in growth and adult
      height over the last century.

PMID- 24126575
TI  - Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell
      line.
AB  - Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression
      of estrogen receptor, progesterone receptor and human epidermal growth factor
      receptor 2. Clinically, TNBC patients are treated with cytotoxic drugs including
      5-fluorouracil (5-FU). However, TNBCs develop resistance to such drugs after a
      series of treatments. To elucidate the mechanisms of drug resistance,
      establishment of drug-resistant cancer cell lines should be one of the most
      useful model systems. However, 5-FU-resistant TNBC cell lines have not been
      previously reported. In this study, we established a 5-FU-resistant cell line,
      MDA-MB-231/5-FU, from the human TNBC cell line MDA-MB-231, by repeated exposure
      to stepwise increases in the concentration of 5-FU. The IC50 value of 5-FU for
      MDA-MB-231/5-FU was 5.5-fold that for the parental cells. The MDA-MB-231/5-FU
      cell line acquired resistance to not only 5-FU, but also vinorelbine, paclitaxel
      and gemcitabine. Additionally, we performed iTRAQ-based quantitative proteomics
      in MDA-MB-231/5-FU cells and the parental cells in order to characterize MDA-MB
      231/5-FU. The proteins upregulated in the newly established cells were mainly
      classified into the categories of 'DNA recombination', 'cell cycle', 'complex
      assembly', 'cytoskeleton organization', 'transport' and 'negative regulation of
      cell death'. These proteins may be related to mechanisms of drug resistance in
      TNBCs. Our established MDA-MB-231/5-FU cell line should be a useful tool for
      identifying new mechanisms of drug resistance and new drug targets in TNBCs.

PMID- 24126577
TI  - Development of an ex vivo lymph node explant model for identification of novel
      molecules active against Leishmania major.
AB  - Leishmaniasis is a vector-borne zoonotic infection affecting people in tropical
      and subtropical regions of the world. Current treatments for cutaneous
      leishmaniasis are difficult to administer, toxic, expensive, and limited in
      effectiveness and availability. Here we describe the development and application
      of a medium-throughput screening approach to identify new drug candidates for
      cutaneous leishmaniasis using an ex vivo lymph node explant culture (ELEC)
      derived from the draining lymph nodes of Leishmania major-infected mice. The ELEC
      supported intracellular amastigote proliferation and contained lymph node cell
      populations (and their secreted products) that enabled the testing of compounds
      within a system that mimicked the immunopathological environment of the infected
      host, which is known to profoundly influence parasite replication, killing, and
      drug efficacy. The activity of known antileishmanial drugs in the ELEC system was
      similar to the activity measured in peritoneal macrophages infected in vitro with
      L. major. Using the ELEC system, we screened a collection of 334 compounds, some
      of which we had demonstrated previously to be active against L. donovani, and
      identified 119 hits, 85% of which were confirmed to be active by determination of
      the 50% effective concentration (EC50). We found 24 compounds (7%) that had an in
      vitro therapeutic index (IVTI; 50% cytotoxic/effective concentration [CC50]/EC50)
      > 100; 19 of the compounds had an EC50 below 1 MUM. According to PubChem searchs,
      17 of those compounds had not previously been reported to be active against
      Leishmania. We expect that this novel method will help to accelerate discovery of
      new drug candidates for treatment of cutaneous leishmaniasis. 

PMID- 24126578
TI  - New 2-thiopyridines as potential candidates for killing both actively growing and
      dormant Mycobacterium tuberculosis cells.
AB  - From in vivo observations, a majority of M. tuberculosis cells in latently
      infected individuals are in a dormant and probably nonculturable state, display
      little metabolic activity, and are phenotypically resistant to antibiotics.
      Despite many attempts, no specific antimicrobials effective against latent
      tuberculosis have yet been found, partly because of a lack of reliable and
      adequate in vitro models for screening of drug candidates. We propose here a
      novel in vitro model of M. tuberculosis dormancy that meets the important
      criteria of latency, namely, nonculturability of cells, considerable reduction of
      metabolic activity, and significant phenotypic resistance to the first-line
      antibiotics rifampin and isoniazid. Using this model, we found a new group of 2
      thiopyridine derivatives that had potent antibacterial activity against both
      actively growing and dormant M. tuberculosis cells. By means of the model of M.
      tuberculosis nonculturability, several new 2-thiopyridine derivatives were found
      to have potent antitubercular activity. The compounds are effective against both
      active and dormant M. tuberculosis cells. The bactericidal effects of compounds
      against dormant M. tuberculosis was confirmed by using three different in vitro
      models of tuberculosis dormancy. The model of nonculturability could be used as a
      reliable tool for screening drug candidates, and 2-thiopyridine derivatives may
      be regarded as prominent compounds for further development of new drugs for
      curing latent M. tuberculosis infection. 

PMID- 24126579
TI  - Terbinafine in combination with other antifungal agents for treatment of
      resistant or refractory mycoses: investigating optimal dosing regimens using a
      physiologically based pharmacokinetic model.
AB  - Terbinafine is increasingly used in combination with other antifungal agents to
      treat resistant or refractory mycoses due to synergistic in vitro antifungal
      activity; high doses are commonly used, but limited data are available on
      systemic exposure, and no assessment of pharmacodynamic target attainment has
      been made. Using a physiologically based pharmacokinetic (PBPK) model for
      terbinafine, this study aimed to predict total and unbound terbinafine
      concentrations in plasma with a range of high-dose regimens and also calculate
      predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine
      concentrations accumulated significantly during the first 28 days of treatment;
      the area under the concentration-time curve (AUC)/MIC ratios and AUC for the
      free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of
      treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose
      regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken
      every 12 h provided the highest systemic exposure; on day 7 of treatment, the
      predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin)
      were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard
      dose regimen of 250 mg once daily. Close agreement was seen between the
      concentrations predicted by the PBPK model and the observed concentrations,
      indicating good predictive performance. This study provides the first report of
      predicted terbinafine exposure in plasma with a range of high-dose regimens. 

PMID- 24126580
TI  - Optimization of pyrrolamides as mycobacterial GyrB ATPase inhibitors: structure
      activity relationship and in vivo efficacy in a mouse model of tuberculosis.
AB  - Moxifloxacin has shown excellent activity against drug-sensitive as well as drug
      resistant tuberculosis (TB), thus confirming DNA gyrase as a clinically validated
      target for discovering novel anti-TB agents. We have identified novel inhibitors
      in the pyrrolamide class which kill Mycobacterium tuberculosis through inhibition
      of ATPase activity catalyzed by the GyrB domain of DNA gyrase. A homology model
      of the M. tuberculosis H37Rv GyrB domain was used for deciphering the structure
      activity relationship and binding interactions of inhibitors with mycobacterial
      GyrB enzyme. Proposed binding interactions were later confirmed through cocrystal
      structure studies with the Mycobacterium smegmatis GyrB ATPase domain. The most
      potent compound in this series inhibited supercoiling activity of DNA gyrase with
      a 50% inhibitory concentration (IC50) of <5 nM, an MIC of 0.03 MUg/ml against M.
      tuberculosis H37Rv, and an MIC90 of <0.25 MUg/ml against 99 drug-resistant
      clinical isolates of M. tuberculosis. The frequency of isolating spontaneous
      resistant mutants was ~10(-6) to 10(-8), and the point mutation mapped to the M.
      tuberculosis GyrB domain (Ser208 Ala), thus confirming its mode of action. The
      best compound tested for in vivo efficacy in the mouse model showed a 1.1-log
      reduction in lung CFU in the acute model and a 0.7-log reduction in the chronic
      model. This class of GyrB inhibitors could be developed as novel anti-TB agents. 

PMID- 24126581
TI  - Preclinical characterization of GSK2336805, a novel inhibitor of hepatitis C
      virus replication that selects for resistance in NS5A.
AB  - GSK2336805 is an inhibitor of hepatitis C virus (HCV) with picomolar activity on
      the standard genotype 1a, 1b, and 2a subgenomic replicons and exhibits a modest
      serum shift. GSK2336805 was not active on 22 RNA and DNA viruses that were
      profiled. We have identified changes in the N-terminal region of NS5A that cause
      a decrease in the activity of GSK2336805. These mutations in the genotype 1b
      replicon showed modest shifts in compound activity (<13-fold), while mutations
      identified in the genotype 1a replicon had a more dramatic impact on potency.
      GSK2336805 retained activity on chimeric replicons containing NS5A patient
      sequences from genotype 1 and patient and consensus sequences for genotypes 4 and
      5 and part of genotype 6. Combination and cross-resistance studies demonstrated
      that GSK2336805 could be used as a component of a multidrug HCV regimen either
      with the current standard of care or in combination with compounds with different
      mechanisms of action that are still progressing through clinical development. 

PMID- 24126582
TI  - Frequency of fks mutations among Candida glabrata isolates from a 10-year global
      collection of bloodstream infection isolates.
AB  - Among 119 echinocandin non-wild-type (non-WT) Candida glabrata strains from two
      global surveys, mutations in fks hot spots (HSs) were detected in 28 (from 7
      countries and 8 U.S. states): 24 strains (85.7%) had non-WT MICs for micafungin,
      22 (78.6%) for anidulafungin, and 25 (89.3%) for caspofungin. The most common FKS
      substitutions among non-WT strains were at positions F659 (n = 7) and S663 (n =
      7). Three isolates displaying WT MIC results had F625Y, L630I, and D632Y
      substitutions or non-HS mutations. Mutations that have been reported to decrease
      the echinocandin binding to the 1,3-beta-d-glucan synthase were categorized as
      resistant by applying the new CLSI breakpoint criteria for all three
      echinocandins. 

PMID- 24126583
TI  - Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for
      treating Stenotrophomonas maltophilia bacteremia?
AB  - A retrospective study was conducted to evaluate the efficacy of levofloxacin in
      the treatment of Stenotrophomonas maltophilia bacteremia. The 30-day mortality
      rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and
      levofloxacin treatment groups. Adverse events related to antibiotics occurred
      more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to
      levofloxacin-resistant S. maltophilia strains developed in patients treated with
      levofloxacin. Our data suggest that levofloxacin can be a useful alternative
      option for treating S. maltophilia infections. 

PMID- 24126584
TI  - Outpatient antibiotic use in France between 2000 and 2010: after the nationwide
      campaign, it is time to focus on the elderly.
AB  - Antibiotic overconsumption is the main force driving the emergence of multidrug
      resistant bacterial strains. To promote better antibiotic use in France, a
      nationwide campaign has been run every year from October to March since 2002. In
      2007, it was shown that winter outpatient antibiotic consumption had decreased by
      26.5% compared to the 2000-2002 baseline period. Here, we quantified outpatient
      antibiotic use between 2000 and 2010 as a follow-up analysis of the nationwide
      campaign. Reimbursed outpatient antibiotic prescriptions were extracted from
      computerized French National Health Insurance databases. Entire series and age
      group and antibiotic class analyses were computed. Time series analyses used
      autoregressive moving-average models with exogenous variables and intervention
      functions. Two periods were considered: October to March "campaign" periods and
      April to September "warm" periods. Compared to the precampaign (2000-2002)
      baseline period, the numbers of weekly antibiotic prescriptions per 1,000
      inhabitants during campaign periods decreased until winter 2006 to 2007 (-30%
      [95% confidence interval {CI}, -36.3 to -23.8%]; P < 0.001) and then stabilized
      except for individuals >60 years of age, for whom prescriptions reached the
      precampaign level. During the warm periods from April to September, no
      significant differences were estimated compared to the baseline level for the
      entire series, but seniors had an increasing trend that became significant as of
      2005, reaching +21% (95% CI, +12.9 to +29.6%) in 2009 (P < 0.0001). These results
      highlight the need for a better understanding of antibiotic use by the elderly,
      requiring research with targeted and tailored public health actions for this
      population. 

PMID- 24126585
TI  - Reevaluation of ceftazidime dosing recommendations in patients on continuous
      ambulatory peritoneal dialysis.
AB  - While intraperitoneal (i.p.) ceftazidime is commonly used to treat continuous
      ambulatory peritoneal dialysis (CAPD)-related infections, the ability of i.p.
      regimens to achieve critical pharmacodynamic targets in both blood and dialysate
      has not been reported. To understand the pharmacodynamic profile of ceftazidime
      during CAPD, data were obtained from a single-dose pharmacokinetic (PK) i.p.
      ceftazidime study that included 10 CAPD patients who received i.p. ceftazidime at
      15 mg/kg of body weight. The probability of target attainment (concentrations
      maintained above the MIC for >60% of the dosing interval [60% T > MIC]) was
      determined for six simulated regimens. A 3-compartment model with each dialysis
      dwell modeled as a separate differential equation was fit to ceftazidime
      concentrations using BigNPAG. Embedded with the final PK model, serum and
      dialysate concentration-time profiles of ceftazidime at 1, 1.5, and 2 g i.p.
      every 24 h (q24h) to q48h were simulated using ADAPT 5. The mean population
      pharmacokinetic parameters were as follows: apparent volume of the central
      compartment (Vc), 7.57 liter; apparent volume of the peritoneal cavity (Vpd),
      2.44 liter; clearance from the central compartment (CL), 0.379 liter/h;
      intercompartmental transfer rate constants (first order) between the central and
      peripheral compartments (k12 and k21), 4.66 and 4.88 h(-1), respectively; and
      intercompartmental transfer rate constants (first order) between the central and
      peritoneal compartments (k13 and k31), 0.111 and 0.227 h(-1), respectively. In
      serum, the probability of target attainment for MICs of <=8 mg/liter exceeded 90%
      for 1.5 to 2 g i.p. q24h to q48h. However, no tested regimen provided adequate
      dialysate exposure at MICs of >=8 mg/liter on day 1 without the use of a 3-g
      loading dose (post hoc analysis). On day 2, 1.5 to 2 g i.p. q24h or 2 g i.p. q48h
      provided adequate exposure in the peritoneal cavity. These results should be
      validated in the presence of infection. Ceftazidime i.p. at 1.5 or 2 g q24h to
      q48h is recommended for nonperitoneal infections. For peritonitis, a 3-g load
      with maintenance dosing of 1 to 2 g i.p. q24h or 2 g i.p. q48h is recommended. 

PMID- 24126586
TI  - Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium
      tuberculosis.
AB  - Drug efflux is an important resistance mechanism in Mycobacterium tuberculosis.
      We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of
      bedaquiline and clofazimine to M. tuberculosis by 8- to 16-fold. This exquisite
      susceptibility was noted among drug-susceptible and drug-resistant clinical
      isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and
      clofazimine, and efflux may emerge as a resistance mechanism to these drugs. 

PMID- 24126588
TI  - Bending the curve on cardiovascular risk.

PMID- 24126587
TI  - KAY-2-41, a novel nucleoside analogue inhibitor of orthopoxviruses in vitro and
      in vivo.
AB  - The availability of adequate treatments for poxvirus infections would be valuable
      not only for human use but also for veterinary use. In the search for novel
      antiviral agents, a 1'-methyl-substituted 4'-thiothymidine nucleoside, designated
      KAY-2-41, emerged as an efficient inhibitor of poxviruses. In vitro, KAY-2-41 was
      active in the micromolar range against orthopoxviruses (OPVs) and against the
      parapoxvirus orf. The compound preserved its antiviral potency against OPVs
      resistant to the reference molecule cidofovir. KAY-2-41 had no noticeable
      toxicity on confluent monolayers, but a cytostatic effect was seen on growing
      cells. Genotyping of vaccinia virus (VACV), cowpox virus, and camelpox virus
      selected for resistance to KAY-2-41 revealed a nucleotide deletion(s) close to
      the ATP binding site or a nucleotide substitution close to the substrate binding
      site in the viral thymidine kinase (TK; J2R) gene. These mutations resulted in
      low levels of resistance to KAY-2-41 ranging from 2.7- to 6.0-fold and cross
      resistance to 5-bromo-2'-deoxyuridine (5-BrdU) but not to cidofovir. The
      antiviral effect of KAY-2-41 relied, at least in part, on activation
      (phosphorylation) by the viral TK, as shown through enzymatic assays. The
      compound protected animals from disease and mortality after a lethal challenge
      with VACV, reduced viral loads in the serum, and abolished virus replication in
      tissues. In conclusion, KAY-2-41 is a promising nucleoside analogue for the
      treatment of poxvirus-induced diseases. Our findings warrant the evaluation of
      additional 1'-carbon-substituted 4'-thiothymidine derivatives as broad-spectrum
      antiviral agents, since this molecule also showed antiviral potency against
      herpes simplex virus 1 in earlier studies. 

PMID- 24126589
TI  - Lupus nephritis: Ancestry, genetic risk and health disparities.
AB  - The disease manifestations and outcomes in lupus nephritis are exceptionally
      heterogeneous. In particular, some ethnic populations are disproportionately
      affected by the most severe forms of the disease. A new study exploring NF-kappaB
      dysregulation and its associated genetic variants might help explain the link
      between ancestry and outcomes in lupus nephritis.

PMID- 24126590
TI  - Proteinuria: Tubular handling of albumin-degradation or salvation?
AB  - In a recent study using transgenic mice with inducible podocyte-specific
      expression of tagged albumin, Tenten and colleagues report transtubular transport
      of albumin, possibly mediated by the neonatal Fc receptor. This study raises
      several questions about the physiological importance of this potential pathway
      and the implications for albuminuria in renal disease.

PMID- 24126591
TI  - Chronic kidney disease: classification of CKD should be about more than
      prognosis.
AB  - Cystatin C continues to show its superiority over serum creatinine in predicting
      mortality among patients with chronic kidney disease (CKD). This superiority is,
      in part, due to the non-glomerular filtration rate (GFR) determinants of cystatin
      C associating with CKD risk factors and outcomes. The definition and
      classification of CKD should not exclusively equate cystatin C with GFR.

PMID- 24126592
TI  - Polycystic kidney disease: TGF-beta signalling and vascular complications in
      ADPKD.

PMID- 24126593
TI  - Diabetes: efficacy of dapagliflozin associated with renal function.

PMID- 24126594
TI  - End-stage renal disease: Link between prehypertension and risk of ESRD grows
      stronger.

PMID- 24126595
TI  - Transforming growth factor-beta1 induces bronchial epithelial cells to
      mesenchymal transition by activating the Snail pathway and promotes airway
      remodeling in asthma.
AB  - Airway remodeling is characterized by airway wall thickening, subepithelial
      fibrosis, increased smooth muscle mass, angiogenesis and an increase in mucous
      glands, which may lead to a chronic and obstinate asthma with pulmonary function
      depression. In the present study, we observed substantially thickened lung tissue
      with extensive fibrosis in ovalbumin-sensitized mice, which was interrelated with
      transforming growth factor-beta1 (TGF-beta1) expression in bronchoalveolar lavage
      fluid. In vitro experiments further demonstrated that TGF-beta1 resulted in
      epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, which was
      characterized by the expected decrease in E-cadherin expression and the increase
      in vimentin and alpha-smooth muscle actin expression, as well as the associated
      increase in Snail expression at mRNA and protein levels. Furthermore, the
      downregulation of Snail by small interfering RNA (siRNA) attenuated the TGF-beta1
      induced EMT-like phenotype. Of note, a significantly increased synthesis of
      fibronectin was observed following TGF-beta1 treatment, which further supported
      the hypothesis that EMT is a pivotal factor in peribronchial fibrosis. In
      combination, the results indicated that myofibroblasts deriving from bronchial
      epithelial cells via EMT may contribute to peribronchial fibrosis and that Snail
      may be an important factor in this phenomenon.

PMID- 24126596
TI  - Managing an extreme peri-implantitis.
AB  - AIM: Peri-implantitis leads to gradual peri-implant bone loss. Severe and extreme
      cases lead to complete implant failure and imply lost implants have to be
      removed. The aim of the present report is to present a case where an extreme peri
      implantitis, causing complete peri-implant bone loss, was managed successfully.
      METHODS: A patient already rehabilitated with a prosthesis supported by two
      implants at positions 3.4 and 3.6 presented with severe peri-implantitis
      affecting both implants. Initial probing depths were 11 and 9 mm respectively.
      Implant at position 3.4 showed a bone-implant gap >=3 mm all around it, but was
      kept firmly in place by the prosthesis, still supported by the other implant. The
      patient refused to have her prosthesis removed. In an attempt to save it anyway,
      after debridement, sandblasting and decontamination of both implant surfaces an
      enzyme-deantigenic collagenic bone substitute was grafted. Controls followed at
      1, 3, 5 and 12 months after surgery. RESULTS: Radiographic exams showed radio
      opacity at the grafted sites to gradually increase over time. Postoperative
      probing depth gain, 7 and 6 mm respectively at position 3.4 and 3.6 remained
      unchanged at all follow-up controls. After 12 months the patient is asymptomatic
      and the failed implant can be considered restored. CONCLUSION: The way we managed
      this extreme peri-implantitis case has allowed to give clinical success even if,
      to comply to the patient's will, the best clinical, evidence-based treatment, was
      not performed. The implant that was otherwise lost was successfully recovered. As
      an hypothesis, a new osseointegration process could have occurred between the
      implant and the newly formed bone.

PMID- 24126597
TI  - Evaluation of the cephalometrics modification of growing Class II Division I
      patients after treatment with the PUL appliance: a pilot study.
AB  - AIM: The aim of this preliminary study was to evaluate short-term dentoskeletal
      changes obtained with a functional appliance for Class II Division I
      malocclusions called propulsor universal light (PUL). METHODS: Fifteen Class II
      Division 1 patients (10.6+/-1.2 years) were consecutively treated by one expert
      operator with PUL appliance and they were compared with a longitudinal group of
      Class II Division I untreated patients (9.9+/-1.9 years) matched for pubertal
      growth spurt stage and sex. Lateral cephalograms were taken before PUL therapy
      and at the end of treatment. The mean duration of treatment was 11.2+/-0.3
      months; t-test or Mann-Whitney U-test was used (P <0.05). RESULTS: Statistically
      significant reduction of the overjet, WITS and ANB was noticed in treated group
      as well as a significant improvement of CoGo and Ramus. CONCLUSION: Class II
      Division I malocclusion in the short term was efficiently treated by PUL
      appliance with both skeletal and dentoalveolar changes.

PMID- 24126598
TI  - Treatment of seriously compromised teeth: decision- making criteria and treatment
      options.
AB  - The aim of this article was to describe the case of a patient who presented to
      our attention with severe periodontal disease, complicated by furcation
      involvement on elements 16 and 17. In addition, the radiographic exam revealed
      the presence of a deep intrabony defect distal to tooth 15. Surgical therapy is
      performed after the resolution of the endodontic component of the intra-bony
      defect on the element 15 and consists on osteoplasty and ostectomy on 16, guided
      tissue regeneration (GTR) on 15, extraction of 17 and bi-laminar connective
      tissue graft for the coverage of the recession on tooth 13. The patient is
      visited monthly and 9 months after surgery, the definitive metal-ceramic crown is
      delivered and adapted to tooth 16. At 18 months, the patient's periodontal
      situation is re-evaluated and the pocket depth results healthy (probing depth of
      tooth 15=2 mm). The surgical practices reported in this work allowed for
      functional and esthetic rehabilitation of periodontally compromised teeth. The
      RSR and the GTR represent conservative surgery that allow the preservation of
      compromised dental elements and if properly performed, guarantee excellent
      survival rates of the elements in the arch. For these reasons, when it is
      possible, the RSR and the GTR are a valid alternative to implantology and are to
      be considered as the first therapeutic option in the treatment plan. 

PMID- 24126599
TI  - Surgical treatment of extensive complex odontoma in the mandible by corticotomy.
      A case report.
AB  - Odontomas represent the most prevalent odontogenic tumors in the jaw. The
      treatment of choice is surgical removal, usually performed by conventional
      techniques involving ostectomies to expose the tumor. In this paper, the authors
      describe, through the report of a case of complex odontoma located in the
      mandibular angle, a more conservative surgical technique called corticotomy, in
      which the bone removed for access to the tumor (buccal cortical) is repositioned
      and fixed by titanium plates of 1.5 mm. 

PMID- 24126600
TI  - Brown tumor of hyperparathyroidism involving craniomaxillofacial region: a rare
      case report and literature review.
AB  - Central giant cell granuloma (CGCG) is a benign, non-odontogenic bone lesion of
      jaw. The condition is relatively infrequent and affects mainly children and young
      adults with a certain predominance among females and exhibits variable
      aggressiveness. Giant cell lesion associated with hyperparathyroidism is known as
      Brown tumor. Brown tumor is one of the bony complications of hyperparathyroidism.
      It is a giant cell granuloma which occurs in osteitis fibrosis cystica. It
      represents the terminal stage of the bone remodelling processes occurring as a
      result of peritrabecular fibrosis and osteoclastic activity. The mandible is the
      predominantly affected site in the maxillofacial area. Maxillary involvement is
      rare. The incidence of Brown tumor associated with hyperparathyroidism is rare
      (0.1%). Here, an extremely rare case of a 20 year old female patient with Brown
      tumor in her maxilla and mandible associated with primary hyperparathyroidism was
      presented. A thorough diagnostic work up showed presence of tumor mass in
      mandible and maxilla and elevated serum alkaline phosphatase and parathormone
      level and the patient was treated for both hyperparathyroidism and Brown tumor
      were discussed. The importance of different radiological evaluation methods and
      the consultation between the oral and maxillofacial surgeons, dentists,
      endocrinologists and radiologists were emphasized. 

PMID- 24126601
TI  - A simple one-step PCR walking method and its application of bacterial rRNA for
      sequencing identification.
AB  - There are many PCR walking methods applied currently, and they all have examples
      of successful application in organisms which are more complex than bacteria.
      However, to a certain extent, it will be more convenient for researchers if the
      complicated operation and poor specificity for bacteria can be improved. Here, we
      introduced an improved one-step PCR walking method of bacteria. Using a specific
      primer of the known sequence together with a universal semi-random primer, the
      unknown sequence adjacent to a known sequence can be obtained easily by just one
      ordinary round PCR. The products can be gel-purified and directly sequenced.
      Specific primers were designed according to the gene sequence of bacterial rRNA,
      and the variable and adjacent gene sequences were obtained by this method. The
      sequence analysis of the product showed that it can improve the resolution of
      bacterial identification to the species level. 

PMID- 24126602
TI  - Extracellular DNA inhibits Salmonella enterica Serovar Typhimurium and S.
      enterica Serovar Typhi biofilm development on abiotic surfaces.
AB  - Extracellular DNA (eDNA) was identified and characterized in a 2-day-old biofilms
      developed by Salmonella enterica ser. Typhimurium SR-11 and S. enterica ser.
      Typhi ST6 using confocal laser scanning microscopy (CLSM) and enzymatic
      extraction methods. Results of microtitre plate assay and CLSM analysis showed
      both Salmonella strains formed significantly more biofilms in the presence of
      DNase I; Furthermore, a remarkable decrease of biofilm formation was observed
      when eDNA was added in the inoculation. However, for the pre-established biofilms
      on polystyrene and glass, no significant difference was observed between the
      DNase I treated biofilm and the corresponding non-treated controls. In
      conclusion, these results demonstrate that eDNA is a novel matrix component of
      Salmonella biofilms. This is the first evidence for the presence of eDNA and its
      inhibitive and destabilizing effect during biofilm development of S. enterica
      ser. Typhimurium and S. enterica ser. Typhi on abiotic surfaces. 

PMID- 24126604
TI  - Palladium nanoparticles deposited on silanized halloysite nanotubes: synthesis,
      characterization and enhanced catalytic property.
AB  - Palladium (Pd) nanoparticles were deposited on the surface of halloysite
      nanotubes (HNTs) modified with gamma-aminopropyltriethoxysilane (APTES) to
      produce Pd/NH2-HNTs nanocomposites. The results indicated that Pd nanoparticles
      were densely immobilized onto NH2-HNTs with an average diameter of ~ 3 nm. The Pd
      distribution on the surface of silanized HNTs showed much more uniform, and the
      Pd nanoparticle size became smaller compared with those directly deposited onto
      HNTs without silanization. Systematic characterization demonstrated that APTES
      were chemically bonded onto HNTs, and further confirmed the bond formation
      between Pd and -NH2 groups, which could ensure the firm deposit of Pd
      nanoparticles on the surface of silanized HNTs. The as-synthesized Pd/NH2-HNTs
      exhibited an excellent catalytic activity in the liquid-phase hydrogenation of
      styrene to ethylbenzene with full conversion within 30 min. The mechanism of the
      deposit of Pd nanoparticles on silanized HNTs was also investigated. 

PMID- 24126603
TI  - Immunogenicity of hypothetical highly conserved proteins as novel antigens in
      Anaplasma marginale.
AB  - Anaplasma marginale is a tick-transmitted Gram-negative intraerythrocytic
      bacterium and the etiological agent of bovine Anaplasmosis. Even though
      considerable research efforts have been undertaken, Anaplasmosis vaccine
      development remains a challenging field. Outer-membrane-specific antigens
      responsible for the ability of more complex immunogens could have a significant
      role in the protective response. Thus, the identification of outer-membrane
      antigens represents a major goal in the development of bacterial vaccines.
      Considering that 40 % of the annotated proteins in A. marginale remain as
      hypothetical, we selected three candidate antigens, AM1108, AM127, and AM216
      based on experimental evidence, in silico structure prediction of beta-barrel
      outer membrane, and orthology clustering. Sequence alignment and analysis
      demonstrated a high degree of conservation for the three proteins between the
      isolates from Argentina compared to the American strains. We confirmed the
      transcription of the three genes in the intraerythrocytic stage. AM1108 and AM216
      recombinant proteins elicited specific T-cell response proliferation and a
      significant rise in TNF-alpha and IFN-gamma transcript levels, respectively. Only
      AM1108 was able to be recognized by specific antibodies from infected bovines.
      This study allowed the identification of new candidate components of the outer
      membrane fraction of A. marginale. Further studies will be required to analyze
      their potential as effective antigens for being included in rational vaccine
      strategies. 

PMID- 24126605
TI  - Rapid atomic layer deposition of silica nanolaminates: synergistic catalysis of
      Lewis/Bronsted acid sites and interfacial interactions.
AB  - Rapid atomic layer deposition (RALD) has been applied to prepare various
      nanolaminates with repeated multilayer structures. The possible reaction pathways
      for RALD of the Al2O3/SiO2 nanolaminate using trimethylaluminum (TMA) and
      tris(tert-butoxy)silanol (TBS) are investigated by using density functional
      theory (DFT) calculations. The introduction of a Lewis-acid catalyst, TMA, can
      result in the formation of the catalytic site, which accelerates the propagation
      of the siloxane polymer. The rate-determining step of whole RALD is the
      elimination of isobutene of the tert-butoxy groups. The Bronsted acid site of
      [AlO4] can catalyze the elimination of isobutene. At the same time, the
      interfacial interactions, such as hydrogen bonding interactions between tert
      butoxy groups and the surface, further catalyze the elimination of isobutene and
      accelerate SiO2 RALD reactions. The synergistic catalysis of Lewis/Bronsted acid
      sites and interfacial interactions may be applied in the RALD fabrication of
      other silica nanolaminates, such as HfO2/SiO2, ZrO2/SiO2, and TiO2/SiO2, in
      microelectronics, catalysis, energy storage, and conversion. 

PMID- 24126606
TI  - White matter integrity alterations in young healthy adults reporting childhood
      trauma: A diffusion tensor imaging study.
AB  - OBJECTIVE: To date, insufficient studies have focused on the relationship between
      childhood trauma and white matter integrity changes in healthy subjects. The aim
      of the present study was to explore the potential effects of childhood trauma on
      white matter microstructural changes by using voxel-based diffusion tensor
      imaging (DTI) to examine alterations in fractional anisotropy (FA) values in a
      group of young healthy adults. METHODS: A total of 21 healthy adults with a
      history of childhood trauma exposures and 21 age- and sex-matched individuals
      without childhood trauma were recruited in the present study. The Childhood
      Trauma Questionnaire was used to assess five aspects of childhood trauma
      exposures. DTI data were obtained on a Philips 3.0-Tesla scanner. Voxel-based
      analysis was conducted to compare white matter FA values between groups. RESULTS:
      Adults with self-reported childhood trauma experiences showed decreased white
      matter FA values in the genu and body of the corpus callosum and the left
      occipital fusiform gyrus (p < 0.001 uncorrected, voxel > 100). There was no
      significant difference in FA values between individuals with single and multiple
      childhood trauma exposures at the defined threshold. CONCLUSION: Our findings
      suggest that childhood trauma is associated with reduced microstructural
      integrity of the white matter in adulthood. These effects are still evident even
      in the absence of current psychiatric or medical symptoms, which may represent
      the vulnerability for developing mental disorders after childhood trauma
      experiences.

PMID- 24126607
TI  - Phenomenological predictors of psychosocial function in bipolar disorder: is
      there evidence that social cognitive and emotion regulation abnormalities
      contribute?
AB  - OBJECTIVES: Neurocognitive ability and mood have often been discussed as
      contributing mechanisms to the severe psychosocial dysfunction experienced in
      bipolar disorder (BD). In contrast, there has been little discussion on the
      contribution of social cognition or emotion regulation. This paper aims to assert
      a potential role for these constructs in psychosocial functioning in BD, with an
      overarching goal to highlight the necessary importance of considering them in
      future research examining psychosocial outcomes in the disorder. METHODS: This
      paper provides a theoretical synthesis of available and indirect evidence for an
      influence of (1) social cognition and (2) emotion regulation on psychosocial
      functioning; it acknowledges important clinical questions that need addressing,
      and discusses how current research might be translated to improve the treatment
      of psychosocial dysfunction in BD. RESULTS: Given their assumed roles in
      facilitating social interactions and modulating behaviours, it is certainly
      plausible that abnormalities in social cognition and emotion regulation are
      detrimental to psychosocial functioning. Currently, there is only minimal direct
      evidence examining their influence, although existing BD studies are
      preliminarily supportive of relationships between these constructs. CONCLUSIONS:
      There are reasonable theoretical grounds, supported by indirect and preliminary
      evidence, to suggest that social cognition and emotion regulation may be
      important in the prediction of psychosocial outcome in BD. However, this
      proposition is limited by the paucity of empirical research directly examining
      this matter.

PMID- 24126609
TI  - Unpublished studies hold twice as much data on drugs as those in public domain,
      study finds.

PMID- 24126608
TI  - Mutations in VRK1 associated with complex motor and sensory axonal neuropathy
      plus microcephaly.
AB  - IMPORTANCE: Patients with rare diseases and complex clinical presentations
      represent a challenge for clinical diagnostics. Genomic approaches are allowing
      the identification of novel variants in genes for very rare disorders, enabling a
      molecular diagnosis. Genomics is also revealing a phenotypic expansion whereby
      the full spectrum of clinical expression conveyed by mutant alleles at a locus
      can be better appreciated. OBJECTIVE: To elucidate the molecular cause of a
      complex neuropathy phenotype in 3 patients by applying genomic sequencing
      strategies. DESIGN, SETTING, AND PARTICIPANTS: Three affected individuals from 2
      unrelated families presented with a complex neuropathy phenotype characterized by
      axonal sensorimotor neuropathy and microcephaly. They were recruited into the
      Centers for Mendelian Genomics research program to identify the molecular cause
      of their phenotype. Whole-genome, targeted whole-exome sequencing, and high
      resolution single-nucleotide polymorphism arrays were performed in genetics
      clinics of tertiary care pediatric hospitals and biomedical research
      institutions. MAIN OUTCOMES AND MEASURES: Whole-genome and whole-exome sequencing
      identified the variants responsible for the patients' clinical phenotype.
      RESULTS: We identified compound heterozygous alleles in 2 affected siblings from
      1 family and a homozygous nonsense variant in the third unrelated patient in the
      vaccinia-related kinase 1 gene (VRK1). In the latter subject, we found a common
      haplotype on which the nonsense mutation occurred and that segregates in the
      Ashkenazi Jewish population. CONCLUSIONS AND RELEVANCE: We report the
      identification of disease-causing alleles in 3 children from 2 unrelated families
      with a previously uncharacterized complex axonal motor and sensory neuropathy
      accompanied by severe nonprogressive microcephaly and cerebral dysgenesis. Our
      data raise the question of whether VRK1 mutations disturb cell cycle progression
      and may result in apoptosis of cells in the nervous system. The application of
      unbiased genomic approaches allows the identification of potentially pathogenic
      mutations in unsuspected genes in highly genetically heterogeneous and
      uncharacterized neurological diseases.

PMID- 24126611
TI  - Effect of exercise training and weight loss on platelet reactivity in overweight
      patients with coronary artery disease.
AB  - PURPOSE: Obesity is associated with increased platelet reactivity. Greater
      platelet reactivity presages adverse events in patients with coronary artery
      disease (CAD). We investigated whether exercise training and weight loss reduce
      platelet reactivity in overweight subjects with CAD. METHODS: Study subjects (N =
      46) were enrolled in a prospective randomized study of exercise training and
      behavioral weight loss, which contrasted the amount of exercise performed (750
      vs. >3000 kcal/week). Platelet reactivity was assessed with the use of flow
      cytometry as the percentage of platelets expressing P-selectin or capable of
      binding fibrinogen in response to 1 MUM adenosine diphosphate in blood before and
      after a 4-month program of exercise and behavioral weight loss. Markers of
      inflammation (high-sensitivity C-reactive protein), procoagulant activity (tissue
      plasminogen activator, plasminogen activator inhibitor 1), insulin sensitivity,
      body composition, physical activity, and fitness were also recorded. RESULTS:
      Platelet reactivity as assessed by P-selectin expression was decreased after
      exercise training and weight loss in study participants (from 34 +/- 17% to 29 +/
      17%; P = .01). The decrease was more pronounced in women (by 13% vs. 2% in men;
      P < .01). The change in platelet reactivity was not independently associated with
      measures of body composition or fitness. After controlling for exercise group and
      gender, the change in platelet reactivity was associated with changes in high
      sensitivity C-reactive protein (r = 0.46) and insulin sensitivity (r = 0.46).
      CONCLUSIONS: In overweight patients with CAD, exercise training and weight loss
      are associated with a decrease in platelet reactivity that may predict an
      improved prognosis.

PMID- 24126613
TI  - Safety and tolerability of sublingual immunotherapy in clinical trials and real
      life.
AB  - PURPOSE OF REVIEW: Sublingual immunotherapy (SLIT) is effective in allergic
      rhinitis and asthma. Apart from its efficacy, safety is crucial as this treatment
      is usually self-administered at home. Tolerability also plays a pivotal role, as
      mild local reactions, although not life-threatening, may represent a risk for
      treatment withdrawal and can therefore negatively affect clinical outcomes. The
      present study addresses this issue by reviewing double-blind, placebo-controlled,
      randomized trials and real-life studies. RECENT FINDINGS: The number of life
      threatening SLIT-related reactions is negligible. SLIT-related adverse events are
      not always consistently reported nor uniformly classified in published studies.
      However, systemic reactions are rare and side effects mostly consist of mild,
      self-limiting local reactions. No treatment-related risk factors for adverse
      events have been clearly defined, as far as type of allergen, dose or schedule.
      SUMMARY: SLIT provides an optimal safety profile both in children and in adults.
      Apart from life-threatening reactions, the lack of standardization of adverse
      events reporting may account for the wide variability of the prevalence of side
      effects in clinical trials and in real-life setting. It can lead to a possible
      underestimation of adverse events, concerning, in particular, local reactions.
      Since poor tolerability may affect adherence and cause treatment discontinuation,
      adopting shared strategies in order to recognize, grade and manage adverse events
      is mandatory.

PMID- 24126612
TI  - Human primary immunodeficiencies causing defects in innate immunity.
AB  - PURPOSE OF REVIEW: There have been exciting recent advances in identifying new
      mutations that cause human primary immunodeficiencies which impact innate immune
      defences. In this review, we will highlight the most important and influential
      advances published in the last 18 months related to the defects of the innate
      immune system. We will also provide clinical context to facilitate the
      incorporation of these discoveries into clinical practice. RECENT FINDINGS: We
      will specifically focus on three areas that have seen recent significant
      advances: defects in Toll-like receptor signalling that enhance susceptibility to
      viral infection, particularly herpes simplex encephalitis; defects in innate
      immunity that impact phagocyte function predisposing to mycobacterial infection;
      and the discovery of genes responsible for isolated congenital asplenia. SUMMARY:
      The field of innate immunodeficiency has benefited greatly from the recent
      improvements in genome sequencing technology and has advanced dramatically in the
      last 18 months. For clinicians confronted with patients with suspected innate
      immunodeficiency, these new discoveries not only increase the likelihood that a
      patient will receive a specific molecular diagnosis and tailored therapy, but
      also add significant complexity to the diagnostic workup. Future challenges will
      include identifying accurate, cost-effective diagnostic approaches to these novel
      immunodeficiencies, so these impressive advances in our understanding of innate
      immunity can be translated into improved health outcomes for our affected
      patients and their families.

PMID- 24126610
TI  - Distributed corpus callosum involvement in amyotrophic lateral sclerosis: a
      deterministic tractography study using q-ball imaging.
AB  - Diffusion tensor imaging (DTI) has become a useful tool for investigating early
      white matter (WM) abnormalities in motor neuron disease. Furthermore, fiber
      tracking packages that apply multi-tensorial algorithms, such as q-ball imaging
      (QBI), have been proposed as alternative approaches to overcome DTI limitations
      in depicting fiber tracts with different orientations within the same voxel. We
      explored motor and extra-motor WM tract abnormalities in phenotypically
      heterogeneous amyotrophic lateral sclerosis (ALS) cases aiming to establish a
      consistent QBI-based WM signature of disease. We performed a whole-brain, QBI
      tract-based spatial statistics analysis with deterministic tractography of genu,
      body and splenium of corpus callosum (CC) and corticospinal tracts (CST) in 20
      ALS patients (12 classical and 8 lower motor neuron variants) compared to 20
      healthy controls. Mean tract length, fiber volume and density, and generalized
      fractional anisotropy were extracted and related to clinical indices of pyramidal
      impairment (upper motor neuron score), disease disability (ALS functional rating
      scale-revised) and progression. ALS patients showed significantly decreased fiber
      density and volume, and increased tract length in all regions of CC and left CST
      (p < 0.05, corrected). In CC body, pyramidal impairment was inversely correlated
      to fiber density (p = 0.01), while in CC splenium, clinical disability (p = 0.01)
      and progression (p = 0.02) were inversely correlated to tract length. Our
      findings further suggest that QBI tractography might represent a promising
      approach for investigating structural alterations in neurodegenerative diseases
      and confirm that callosal involvement is a consistent feature of most ALS
      variants, significantly related to both pyramidal dysfunction and disease
      disability.

PMID- 24126614
TI  - B-cell memory and primary immune deficiencies: interleukin-21 related defects.
AB  - PURPOSE OF REVIEW: The purpose of this study is to describe recent advances in
      our understanding of the role of interleukin-21 (IL-21) in B-cell maturation, and
      how defects in IL-21 receptor (IL-21R) signalling pathways (IL
      21R/gammac/JAK3/STAT3) are related to primary immune deficiencies. RECENT
      FINDINGS: Abnormal signalling through IL-21R/gammac/JAK3/STAT3 pathway has been
      related to decreased specific antibody responses following vaccination, and to
      increased susceptibility to encapsulated bacterial infections. This is manifested
      in the hyper-IgE syndrome, X-linked and JAK3-related severe combined
      immunodeficiency (SCID) and loss-of-function mutations in the IL-21R gene. Common
      variable immunodeficiency is associated with impaired in-vitro development of
      peripheral blood mononuclear cells or purified B-cells into memory or CD38 B
      cells following addition of IL-21. SUMMARY: IL-21 is a key cytokine in
      development of B-cells into immunoglobulin-secreting cells. Abnormal signalling
      through the IL-21R/gammac/JAK3/STAT3 pathway leads to defective humoral immune
      responses to both T-dependent and T-independent antigens and impairs the
      establishment of long-lasting B-cell memory. Studies involving patients with
      hyper-IgE syndrome demonstrated the nonredundant role of STAT3 in B-cell
      production of high-affinity specific antibodies, while total serum
      immunoglobulins could be maintained through STAT3-independent activation of AID
      (activation-induced cytidine-deaminase). IL-21 related defects may also be
      associated with reduced natural killer (NK)-cell cytotoxicity and TH17 cytokine
      production, indicating that abnormalities in the IL-21-IL-21R pathway have
      profound effects on crucial immune responses.

PMID- 24126615
TI  - Subcutaneous immunoglobulin replacement therapy: the European experience.
AB  - PURPOSE OF REVIEW: Rapid subcutaneous immunoglobulin (SCIg) infusions have been
      used as an important method of delivering replacement immunoglobulin (Ig) to
      patients with primary immune deficiencies (PIDs) in Europe over the last 25
      years. This review provides a comprehensive interpretation of the literature
      relating to the administration of SCIg and the services that have been developed
      alongside. RECENT FINDINGS: Using rates of at least 20 ml/h per infusion site and
      simultaneous sites, the infusion time once per week is short (1-2 h in adults)
      and using small portable pumps, the child or adult is free for other activities
      during the therapy. The rapid SCIg infusions have been documented as well
      tolerated, efficacious and acceptable to infants and their parents, children,
      adults and elderly patients, and more recently to patients with autoimmunity
      requiring immunomodulatory Ig doses. SUMMARY: As part of PID diagnostic and
      management services, educational programmes for self-infusion of both intravenous
      Ig and SCIg at home have been developed throughout Europe, resulting in increased
      patient compliance and patient empowerment as well as cost-savings for healthcare
      providers.

PMID- 24126616
TI  - Skeletal manifestations of treatment of breast cancer on premenopausal women.
AB  - With increasing use of screening mammography and more effective adjuvant systemic
      therapies, the majority of women diagnosed with early stage breast cancer will be
      long-term survivors and experience personal cures. Among the common side effects
      of adjuvant therapies is treatment-related bone loss, primarily as a result of
      estrogen deprivation. Whereas this occurs in both postmenopausal and
      premenopausal women, this brief review will focus on pre- or perimenopausal women
      when initially diagnosed with breast cancer. An important distinction is between
      those women who retain ovarian function despite cancer or preventative treatments
      and the more common situation of premenopausal women who as result of cancer
      treatments undergo ovarian failure or early menopause. Some women with treatment
      related ovarian failure will have sufficient treatment-related bone loss to be at
      increased risks of subsequent nontraumatic fractures and/or osteoporosis and will
      be candidates for antiresorptive treatments. The noncancer treatment risk
      factors, screening and treatments for the management of osteopenia and
      osteoporosis are generally the same in postmenopausal women with and without
      breast cancer. However, premenopausal women with relatively rapid onset of
      treatment-related ovarian failure and bone loss pose several challenges.
      Awareness of treatment-related bone loss and risks of subsequent osteoporosis is
      a high priority in an ever-increasing population of breast cancer survivors. 

PMID- 24126618
TI  - An active one-lobe pulmonary simulator with compliance control for medical
      training in neonatal mechanical ventilation.
AB  - Mechanical ventilation is a current support therapy for newborns affected by
      respiratory diseases. However, several side effects have been observed after
      treatment, making it mandatory for physicians to determine more suitable
      approaches. High fidelity simulation is an efficient educational technique that
      recreates clinical experience. The aim of the present study is the design of an
      innovative and versatile neonatal respiratory simulator which could be useful in
      training courses for physicians and nurses as for mechanical ventilation. A
      single chamber prototype, reproducing a pulmonary lobe both in size and function,
      was designed and assembled. Volume and pressure within the chamber can be tuned
      by the operator through the device control system, in order to simulate both
      spontaneous and assisted breathing. An innovative software-based simulator for
      training neonatologists and nurses within the continuing medical education
      program on respiratory disease management was validated. Following the clinical
      needs, three friendly graphic user interfaces were implemented for simulating
      three different clinical scenarios (spontaneous breathing, controlled breathing
      and triggered/assisted ventilation modalities) thus providing physicians with an
      active experience. The proposed pulmonary simulator has the potential to be
      included in the range of computer-driven technologies used in medical training,
      adding novel functions and improving simulation results. 

PMID- 24126617
TI  - The use of train of four monitoring for clinical evaluation of the axillary
      brachial plexus block.
AB  - The axillary approach of brachial plexus anesthesia is the most commonly used
      technique for forearm and hand surgery. Dynamometer is known as objective test
      for the clinical assessment of motor block of the nerves in brachial plexus
      block. However, the use of this device may not always be practical in operating
      room. The train-of-four (TOF) test is a non-invasive peripheral nerve stimulator
      that shows the level of motor block of muscle relaxants. The aim of the study is
      to investigate the use of TOF testing as a peripheral nerve stimulator for
      objective clinical evaluation of motor block at axillary brachial plexus block.
      44 patients were randomized according to the development of partial or complete
      motor in the axillary brachial plexus block. The nerves were selectively
      localized by nerve stimulation and ultrasound guidance. After obtaining an
      appropriate peripheral motor response, predetermined volumes of bupivacaine were
      selectively injected to the 4 nerves. Sensory, motor block levels and TOF values
      were measured at 10th, 20th, 30th minutes immediately after the axillary brachial
      plexus block. TOF values were gradually decreased and significant difference was
      observed between the development of a complete and partial motor block at 30th
      minute. TOF values were also significantly less in patients of complete sensory
      block than the patients of partial sensory block at 30th minute. The use of TOF
      monitoring may be beneficial to assess the objective clinical effect of motor
      block in the patients with axillary brachial plexus nerve block. 

PMID- 24126619
TI  - Autophagy sensitivity of neuroendocrine lung tumor cells.
AB  - Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including
      low-grade typical and intermediate-grade atypical carcinoid, high-grade large
      cell NE carcinoma and small cell lung carcinoma. Currently, no effective
      treatments are available to cure NE lung tumors, demanding identification of
      biological features specific to these tumors. Here, we report that autophagy has
      an important role for NE lung tumor cell proliferation and survival. We found
      that the expression levels of the autophagy marker LC3 are relatively high in a
      panel of lung tumor cell lines expressing high levels of neuron-specific enolase
      (NSE), a key NE marker in lung tumors. In response to bafilomycin A1 and
      chloroquine, NE lung tumor cells exhibited cytotoxicity whereas non-NE lung tumor
      cells exhibited cytostasis, indicating a distinct role of autophagy for NE lung
      tumor cell survival. Intriguingly, in certain NE lung tumor cell lines, the
      levels of processed LC3 (LC3-II) were inversely correlated with AKT activity.
      When AKT activity was inhibited using AKTi or MK2206, the levels of LC3-II and
      SQSTM1/p62 were increased. In contrast, torin 1, rapamycin or mTOR knockdown
      increased p62 levels, suggesting that these two pathways have opposing effects on
      autophagy in certain NE lung tumors. Moreover, inhibition of one pathway resulted
      in reduced activity of the other, suggesting that these two pathways crosstalk in
      the tumors. These results suggest that NE lung tumor cells share a common feature
      of autophagy and are more sensitive to autophagy inhibition than non-NE lung
      tumor cells.

PMID- 24126620
TI  - Aortic valve area assessed with 320-detector computed tomography: comparison with
      transthoracic echocardiography.
AB  - To evaluate the diagnostic accuracy of aortic valve area (AVA) assessment with
      320-detector Computed Tomography (MDCT) compared to transthoracic
      echocardiography (TTE) in a population with mild to severe aortic valve stenosis.
      AVA was estimated in 169 patients by planimetry on MDCT images (AVA(MDCT)) and by
      the continuity equation with TTE (AVA(TTE)). To generate a reference AVA
      (AVA(REF)) we used the stroke volume from MDCT divided by the velocity time
      integral from CW Doppler by TTE (according to the continuity equation: stroke
      volume in LVOT = stroke volume passing the aortic valve). AVA(REF) was used as
      the reference to compare both measures against, since it bypasses the assumption
      of LVOT being circular in the continuity equation and the potential placement
      error of PW Doppler in the LVOT. The mean (+/-SD) age of the patients was 71 (+/
      9) years, 113 (67%) were males. Mean AVA(TTE) was 0.93 (+/-0.33) cm(2), mean
      AVA(MDCT) was 0.99 (+/-0.36) cm(2) and mean AVA(REF) was 1.00 (+/-0.39) cm(2).
      The mean difference between AVA(TTE) and AVA(MDCT) was -0.06 cm(2), p = 0.001,
      mean difference between AVA(TTE) and AVA(REF) was -0.06 cm(2), p < 0.001, and
      mean difference between AVA(MDCT) and AVA(REF) was -0.01 cm(2), p = 0.60.
      Calcification of the aortic valve quantified by Agatston score, significantly
      decreased the correlation between AVA(MDCT) and AVA(REF), (r low Agatston = 0.90,
      r high Agatston = 0.57). MDCT measured AVA is slightly larger than AVA measured
      by TTE (0.06 cm(2)). The accuracy and precision errors on AVA measurements are
      comparable for MDCT and TTE. Valvular calcification may primarily affect the
      accuracy of AVA(MDCT).

PMID- 24126621
TI  - Detection of respiratory viruses using a multiplex real-time PCR assay in
      Germany, 2009/10.
AB  - The aim of this study was to determine the prevalence of respiratory viruses and
      to prospectively evaluate the performance of the fast-track diagnostics (FTD)
      respiratory pathogens multiplex PCR assay shortly after the 2009/10 influenza
      pandemic. Highly sensitive monoplex real-time PCR assays served as references.
      Discrepant results were further analyzed by the xTAG RVP Fast assay. A total of
      369 respiratory samples from children and adults were collected prospectively in
      Germany from December 2009 until June 2010. The sensitivity and specificity of
      the FTD assay after resolution of discrepant results was 92.2 % and 99.5 %,
      respectively. Lowest specificity of the FTD assay was observed for human
      bocavirus. Multiple detections were recorded in 33/369 (8.9 %) of the samples by
      monoplex PCR and in 43/369 (11.7 %) using the FTD assay. The most prevalent
      viruses were respiratory syncytial virus and human metapneumovirus. Only pandemic
      influenza virus A/H1N1 (2009), and not seasonal influenza virus, was detected.
      Viruses other than influenza virus accounted for the majority of acute
      respiratory infections. The FTD assay can be easily implemented in general
      diagnostic laboratories and facilitate the optimization of patient-management
      schemes. 

PMID- 24126622
TI  - Presenting quantitative information about placebo rates to patients.

PMID- 24126623
TI  - Epilepsy: Genetic variant in subtype of MTLE.

PMID- 24126624
TI  - Epilepsy: Guidelines on vagus nerve stimulation for epilepsy.

PMID- 24126626
TI  - Infectious disease: Conjugate vaccine is effective against serogroup A
      meningococcal meningitis.

PMID- 24126625
TI  - Neurothrombectomy in the treatment of acute ischaemic stroke.
AB  - Major ischaemic stroke is a leading cause of morbidity and mortality in
      industrialized countries. For patients with acute stroke, fast and effective
      vessel recanalization is important for successful treatment. Neurothrombectomy-
      that is, angiographically performed mechanical thrombus removal from intracranial
      arteries--results in higher recanalization rates than with pharmaceutical
      thrombolysis alone, but the value of this treatment in terms of clinical outcome
      remains to be established. This article summarizes the history of intra-arterial
      stroke treatment, outlines the recent developments and the different techniques
      used, and discusses the results of current studies on neurothrombectomy. Owing to
      the high morphological and clinical variability of stroke, careful patient
      selection in future randomized controlled trials will be crucial for assessment
      of the true potential of neurothrombectomy.

PMID- 24126628
TI  - Neuro-oncology: Novel molecular targets in treatment of glioblastoma.

PMID- 24126627
TI  - NURR1 in Parkinson disease--from pathogenesis to therapeutic potential.
AB  - In Parkinson disease (PD), affected midbrain dopamine (DA) neurons lose specific
      dopaminergic properties before the neurons die. How the phenotype of DA neurons
      is normally established and the ways in which pathology affects the maintenance
      of cell identity are, therefore, important considerations. Orphan nuclear
      receptor NURR1 (NURR1, also known as NR4A2) is involved in the differentiation of
      midbrain DA neurons, but also has an important role in the adult brain. Emerging
      evidence indicates that impaired NURR1 function might contribute to the
      pathogenesis of PD: NURR1 and its transcriptional targets are downregulated in
      midbrain DA neurons that express high levels of the disease-causing protein alpha
      synuclein. Clinical and experimental data indicate that disrupted NURR1 function
      contributes to induction of DA neuron dysfunction, which is seen in early stages
      of PD. The likely involvement of NURR1 in the development and progression of PD
      makes this protein a potentially interesting target for therapeutic intervention.

PMID- 24126630
TI  - Genetics: Utility of next-generation sequencing in ataxias.

PMID- 24126631
TI  - Direct measurements of non-ionic attraction and nanoscaled lubrication in
      biomimetic composites from nanofibrillated cellulose and modified
      carboxymethylated cellulose.
AB  - There is a growing interest to design biomimetic self-assembled composite films
      from renewable resources aimed at a combination of high toughness, strength and
      stiffness. However, the relationship between interfacial interactions of the
      components and the mechanical performance of the composite is still poorly
      understood. In this work we present evidence of the link between mechanical
      performance of carbohydrate-based composites with nanolubrication and with direct
      surface forces between the hard and soft domain in the system. Our approach was
      to use nanofibrillated cellulose (NFC) as the major reinforcing domain and to
      modify it by adsorption of a small amount of soft polyethylene glycol grafted
      carboxymethyl cellulose (CMC-g-PEG). The effect of the soft polymer on direct
      normal and friction forces in air between cellulose surfaces was evaluated using
      colloidal probe microscopy. The fibrillar structure of the NFC thin film affected
      the frictional behaviour; when decreasing load, the friction between pure
      cellulose surfaces increased, suggesting partial pull-out of fibrils, a
      phenomenon not observed for non-fibrillar cellulose substrates. Adsorption of CMC
      g-PEG on both surfaces decreased the friction considerably but adhesion was still
      high. The symmetric system, having both cellulose substrates covered with the
      polymer, was compared to asymmetric systems where only one surface was covered
      with the polymer. Furthermore, a free standing composite film was prepared by non
      ionic self-assembly of NFC and CMC-g-PEG with 99 : 1 weight-ratio; the mechanical
      properties of the macroscopic films were related to the nanoscaled interactions
      between the components. The composition studied showed excellent mechanical
      properties which do not follow the simple rule of mixture. Thus, a synergy in the
      direct surface forces and mechanical properties was found. This approach offers a
      robust path to aid in the efficient design of next generation biomimetic
      composites. 

PMID- 24126629
TI  - The epidemiology of ALS: a conspiracy of genes, environment and time.
AB  - Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive
      neurodegenerative disease of motor neurons, resulting in worsening weakness of
      voluntary muscles until death from respiratory failure occurs after about 3
      years. Although great advances have been made in our understanding of the genetic
      causes of ALS, the contribution of environmental factors has been more difficult
      to assess. Large-scale studies of the clinical patterns of ALS, individual
      histories preceding the onset of ALS, and the rates of ALS in different
      populations and groups have led to improved patient care, but have not yet
      revealed a replicable, definitive environmental risk factor. In this Review, we
      outline what is currently known of the environmental and genetic epidemiology of
      ALS, describe the current state of the art with respect to the different types of
      ALS, and explore whether ALS should be considered a single disease or a syndrome.
      We examine the relationship between genetic and environmental risk factors, and
      propose a disease model in which ALS is considered to be the result of
      environmental risks and time acting on a pre-existing genetic load, followed by
      an automatic, self-perpetuating decline to death. 

PMID- 24126632
TI  - Revised Atlanta and determinant-based classification: application in a
      prospective cohort of acute pancreatitis patients.
AB  - OBJECTIVES: Atlanta classification (Atlanta 1992) of acute pancreatitis (AP) has
      several limitations. Two new classification systems were recently proposed: the
      Atlanta reclassification (Atlanta 2012) and the determinant-based classification
      (DBC). The aim of our study was to: (i) determine the association between
      different severity categories and clinical outcomes and (ii) perform a head-to
      head comparison between Atlanta 1992, Atlanta 2012, and DBC in predicting these
      clinical outcomes. METHODS: A total of 256 prospectively enrolled patients were
      assigned a severity category for all three classifications. Five clinical
      outcomes were evaluated: mortality, intensive care unit (ICU) admission and
      length of stay (LOS), need for interventions, and hospital LOS. Pairwise testing
      between severity grades within a classification system was performed using
      Fisher's exact and Kruskal-Wallis tests. Predictive accuracies were evaluated
      using area under the ROC curve (AUC) and Somer's D co-efficient. RESULTS:
      Overall, higher grades of severity were associated with worse clinical outcomes
      for all three classification systems. Atlanta 2012 and DBC performed better than
      Atlanta 1992 and were comparable in predicting mortality (AUC 0.89 for both vs.
      0.76, P<0.001), ICU admission (AUC 0.91 for both vs. 0.80, P<0.001), and ICU LOS
      (Somer's D 0.21 and 0.28 vs. 0.07, P<0.05). DBC performed better in predicting
      need for interventions (AUC 0.93 vs. 0.85, P<0.001), whereas Atlanta 2012
      performed better in predicting hospital LOS (Somer's D 0.43 vs. 0.37, P=0.04).
      CONCLUSIONS: Atlanta 2012 and DBC severity categories accurately reflected
      clinical outcomes in our cohort and were superior to Atlanta 1992. These novel
      classification systems can guide the selection of homogeneous patient populations
      for clinical research and provide an accurate spectrum of disease severity
      categories in the clinical setting.

PMID- 24126633
TI  - EMerging BiomARKers in Inflammatory Bowel Disease (EMBARK) study identifies fecal
      calprotectin, serum MMP9, and serum IL-22 as a novel combination of biomarkers
      for Crohn's disease activity: role of cross-sectional imaging.
AB  - OBJECTIVES: In Crohn's disease (CD), clinical symptoms correspond poorly to
      inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall
      inflammation would be useful to monitor disease activity. The EMBARK study
      evaluated disease activity in patients with ulcerative colitis (UC) and CD, and
      used endoscopy with or without cross-sectional imaging for biomarker discovery.
      METHODS: UC (n=107) and CD (n=157) patients were characterized and underwent
      ileocolonoscopy (ICO). A subset of CD patients (n=66) also underwent computed
      tomography enterography (CTE). ICO and CTE were scored by a gastroenterologist
      and radiologist who incorporated findings of inflammation into a single score
      (ICO-CTE) for patients that underwent both procedures. Serum and fecal biomarkers
      were evaluated for association with the Mayo Clinic endoscopy score in UC
      patients and with ICO alone or ICO-CTE in CD patients. Individual biomarkers with
      a moderate degree of correlation (P<=0.3) were evaluated using multivariate
      analysis with model selection using a stepwise procedure. RESULTS: In UC, ordinal
      logistic regression using Mayo Clinic endoscopy subscore selected the combination
      of fecal calprotectin and serum matrix metalloproteinase 9 (MMP9; pseudo
      R(2)=0.353). In CD, we found that use of the ICO-CTE increased specificity of
      known biomarkers. Using ICO-CTE as the dependent variable for biomarker
      discovery, the selected biomarkers were the combination of fecal calprotectin,
      serum MMP9, and serum IL-22 (r=0.699). CONCLUSIONS: Incorporation of both ICO and
      CTE into a single measure increased biomarker performance in CD. Combinations of
      fecal calprotectin and serum MMP9 for UC, and combinations of fecal calprotectin,
      serum MMP9, and serum interleukin-22 in CD, demonstrated the strongest
      association with imaging/endoscopy-defined inflammation.

PMID- 24126634
TI  - Two-dimensional stimulated resonance Raman spectroscopy study of the Trp-cage
      peptide folding.
AB  - We report a combined molecular dynamics (MD) and ab initio simulation study of
      the ultrafast broadband ultraviolet (UV) stimulated resonance Raman (SRR) spectra
      of the Trp-cage mini protein. Characteristic two dimensional (2D) SRR features of
      various folding states are identified. Structural fluctuations erode the cross
      peaks and the correlation between diagonal peaks is a good indicator of the alpha
      helix formation. 

PMID- 24126635
TI  - Robertkochia marina gen. nov., sp. nov., of the family Flavobacteriaceae,
      isolated from surface seawater, and emended descriptions of the genera Joostella
      and Galbibacter.
AB  - A Gram-staining-negative, orange-pigmented, strictly aerobic, carotenoid
      producing, rod-shaped, non-flagellated, non-spore-forming bacterium, motile by
      gliding, designated strain CC-AMO-30D(T), was isolated from surface seawater
      collected near Taichung harbour, Taiwan. Strain CC-AMO-30D(T) shared pairwise 16S
      rRNA gene sequence similarities of 94.8, 93.7 and 92.5% with the type strains of
      the type species of the genera Joostella, Pustulibacterium and Galbibacter,
      respectively, and formed a distinct monophyletic lineage in phylogenetic trees.
      The major fatty acids (>= 5% of total) were iso-C15 : 1 G, iso-C15 : 0, iso-C17 :
      0 3-OH, iso-C15 : 0 3-OH, iso-C16 : 0 and anteiso-C15 : 0. The polar lipid
      profile consisted of phosphatidylethanolamine, four unidentified lipids, two
      unidentified aminolipids and an unidentified phospholipid. The major polyamine
      was the triamine sym-homospermidine. The DNA G+C content was 47.1 mol% and the
      predominant respiratory quinone was menaquinone-6 (MK-6). Based on the
      phylogenetic distinctiveness and distinguishing phenotypic characteristics,
      strain CC-AMO-30D(T) represents a novel genus and species of the family
      Flavobacteriaceae, for which the name Robertkochia marina gen. nov., sp. nov. is
      proposed; the type strain of the type species Robertkochia marina is CC-AMO
      30D(T) ( = JCM 18552(T) = BCRC 80469(T)). Emended descriptions of the genera
      Joostella and Galbibacter are also proposed.

PMID- 24126636
TI  - Zunongwangia mangrovi sp. nov., isolated from mangrove (Avicennia marina)
      rhizosphere, and emended description of the genus Zunongwangia.
AB  - A Gram-stain-negative, strictly aerobic, slightly halophilic, non-motile and rod
      shaped bacterial strain, designated P2E16(T), was isolated from mangrove
      (Avicennia marina) rhizosphere, collected at Devipattinam mangroves, Tamil Nadu,
      India. Strain P2E16(T) grew optimally at pH 7.0-8.0, at 25-28  degrees C and in
      the presence of 2-3% (w/v) NaCl. 16S rRNA gene analysis showed that strain
      P2E16(T) was phylogenetically closely related to the genus Zunongwangia, with
      Zunongwangia profunda SM-A87(T) as the closest related type strain (98.2% 16S
      rRNA gene sequence similarity) and less than 93% 16S rRNA gene sequence
      similarity to all other members of the family Flavobacteriaceae. Strain P2E16(T)
      contained MK-6 as the major respiratory quinone, phosphatidylethanolamine as the
      predominant polar lipid and iso-C(15 : 0) (17.8%), iso-C(17 : 0) 3-OH (15.1%),
      C(15 : 0) (12.8%), iso-C(17 : 1)omega9c (9.8%), iso-C(15 : 1) G (9.0%), and
      summed feature 3 (comprising C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH; 7.1%) as
      the major fatty acids. The DNA G+C content was 34.3 mol%. Differential phenotypic
      properties, together with the phylogenetic distinctiveness and low DNA-DNA
      relatedness demonstrated that strain P2E16(T) was distinct from the type strain
      of Zunongwangia profunda. On the basis of these presented data, strain P2E16(T)
      is considered to represent a novel species of the genus Zunongwangia, for which
      the name Zunongwangia mangrovi sp. nov. is proposed. The type strain is P2E16(T)
      ( = DSM 24499(T) = LMG 26237(T) = KCTC 23496(T)). An emended description of the
      genus Zunongwangia is also provided.

PMID- 24126637
TI  - Wickerhamomyces sylviae f.a., sp. nov., an ascomycetous yeast species isolated
      from migratory birds.
AB  - In the present work, we investigated the phylogenetic position and phenotypic
      characteristics of eight yeast isolates collected from migratory birds on the
      island of Ustica, Italy. A phylogenetic analysis based on the D1/D2 region of the
      large-subunit rRNA gene showed that all isolates clustered as a single separate
      lineage within the Wickerhamomyces clade. They exhibited distinct morphological
      and physiological characteristics and were clearly separated from their closest
      relatives, Wickerhamomyces lynferdii, Wickerhamomyces anomalus and
      Wickerhamomyces subpelliculosus, in blastn searches. On the basis of the
      isolation source, physiological features and molecular strain typing carried out
      with randomly amplified polymorphic DNA (RAPD)-PCR and minisatellite-primed (MSP)
      PCR analysis, the isolates were identified as strains of the same species. The
      name Wickerhamomyces sylviae f.a., sp. nov. is proposed to accommodate these
      novel strains; the type strain is U88A2(T) ( = PYCC 6345(T) = CBS 12888(T)). The
      MycoBank number is MB 804762. 

PMID- 24126638
TI  - Tumor necrosis factor-alpha induces ADAMTS-4 expression in human osteoarthritis
      chondrocytes.
AB  - Tumor necrosis factor (TNF)-alpha and a disintegrin and metalloproteinase with
      thrombospondin motifs 4 (ADAMTS-4) are important in osteoarthritis (OA) cartilage
      degradation. In the present study, we explored the interaction between the two
      proteins by examining the effect of TNF-alpha on ADAMTS-4 expression and activity
      in osteoarthritic chondrocytes. Human osteoarthritic chondrocytes were treated
      with TNF-alpha in different concentrations (5, 15, 30, 45 and 60 ng/ml) for
      different lengths of time (1, 6, 12, 18 and 24 h) with or without the TNF
      receptor 1 (TNFR1) inhibitor SPD304 or different kinase inhibitors. TNF-alpha
      increased the ADAMTS-4 mRNA level in a statistically significant dose- and time
      dependent manner within 18 h, which was reflected in the dose-dependent induction
      of the ADAMTS-4 promoter activity, ADAMTS-4 protein expression and ADAMTS-4
      activity. SPD304 (50 uM) and p38 mitogen-activated protein kinase (MAPK) siRNA
      and inhibitor PD169316 (25 uM) completely eradicated the promoting effect of TNF
      alpha on ADAMTS-4 expression and activity. TNF-alpha induces ADAMTS-4 expression
      and activity in human osteoarthritic chondrocytes at the transcriptional level
      via TNFR1 by a p38 MAPK-dependent mechanism. To the best of our knowledge, this
      is the first evidence of crosstalk between TNF-alpha and ADAMTS-4 in relation to
      OA cartilage degradation, which adds novel insight into the pathophysiology of OA
      and cartilage degradation.

PMID- 24126639
TI  - Tribulations of stroke trials.

PMID- 24126640
TI  - Endovascular treatment of unruptured and ruptured brain arteriovenous
      malformations with Onyx18: a monocentric series of 84 patients.
AB  - BACKGROUND: Brain arteriovenous malformations (AVMs) are a rare pathology, and
      their treatment is discussed. The development of techniques and materials in
      endovascular, radiosurgical, and neurosurgical fields led to higher rates of
      complete occlusions and good clinical outcomes. MATERIALS AND METHODS: 84
      patients (52 men, 32 women; mean age 38.2 years; range, 9-70 years) were treated
      at our institution with Onyx18 from 2001 to 2011. Patients treated with other
      embolic agents, with micro-AVMs, were not included in the analysis. RESULTS:
      Complete occlusion was achieved in 27/84 patients (32.2%), in 40/84 (47.6%) brain
      AVMs occlusion of 80-90% of the nidus was obtained, and in 17/84 (20.3%) cases
      <80% of the nidus was occluded. Intraprocedural adverse events occurred in 11/84
      patients (13.1%), and overall mortality and disabling permanent morbidity were
      2.3% (2/84) and 4.7% (4/84), respectively. CONCLUSIONS: Endovascular treatment
      may be considered a safe and effective approach in superficial small brain AVMs
      in addition to surgery, mostly in ruptured AVMs. The therapeutic strategy should
      be to cure small and medium AVMs with endovascular treatment alone or combined
      treatment. Large unruptured AVMs (Spetzler-Martin grades IV-V) should be treated
      with target embolization of high flow fistulas or intranidal aneurysms.

PMID- 24126641
TI  - Prevalence and risk factors of lumbar spondylolisthesis in elderly Chinese men
      and women.
AB  - OBJECTIVE: A screening survey for osteoporotic fractures in men and women in Hong
      Kong represents the first large-scale prospective population-based study on bone
      health in elderly (>=65 years) Chinese men and women. This study aims to identify
      the prevalence and potential risk factors of lumbar spondylolisthesis in these
      subjects. METHODS: The lateral lumbar radiographs of 1,994 male and 1,996 female
      patients were analysed using the Meyerding classification. RESULTS: Amongst the
      men, 380 (19.1%) had at least one spondylolisthesis and 43 (11.3%) had slips at
      two or more levels; 283 had anterolisthesis, 85 had retrolisthesis, whereas 12
      subjects had both anterolisthesis and retrolisthesis. Amongst the women, 499
      (25.0%) had at least one spondylolisthesis and 69 (13.8%) had slips at two or
      more levels; 459 had anterolisthesis, 34 had retrolisthesis, whereas 6 subjects
      had both anterolisthesis and retrolisthesis. Advanced age, short height, higher
      body mass index (BMI), higher bone mineral density (BMD) and degenerative
      arthritis are associated with spondylolisthesis. Lower Physical Activity Scale
      for the Elderly (PASE) score was associated with spondylolisthesis in men; higher
      body weight, angina and lower grip strength were associated with
      spondylolisthesis in women. CONCLUSION: The male/female ratio of lumbar
      spondylolisthesis prevalence was 1:1.3 in elderly Chinese. Men are more likely to
      have retrolisthesis. KEY POINTS: * The prevalence of spondylolisthesis is 19.1%
      in elderly Chinese men. * The prevalence of spondylolisthesis is 25.0% in elderly
      Chinese women. * Men are more likely to have retrolisthesis. * Anterolisthesis is
      most commonly seen at the L4/L5 level. * Retrolisthesis is most commonly seen at
      the L3/L4 level.

PMID- 24126642
TI  - Radiation dose reduction in cerebral CT perfusion imaging using iterative
      reconstruction.
AB  - OBJECTIVES: To investigate whether iterative reconstruction (IR) in cerebral CT
      perfusion (CTP) allows for 50% dose reduction while maintaining image quality
      (IQ). METHODS: A total of 48 CTP examinations were reconstructed into a standard
      dose (150 mAs) with filtered back projection (FBP) and half-dose (75 mAs) with
      two strengths of IR (middle and high). Objective IQ (quantitative perfusion
      values, contrast-to-noise ratio (CNR), penumbra, infarct area and
      penumbra/infarct (P/I) index) and subjective IQ (diagnostic IQ on a four-point
      Likert scale and overall IQ binomial) were compared among the reconstructions.
      RESULTS: Half-dose CTP with high IR level had, compared with standard dose with
      FBP, similar objective (grey matter cerebral blood volume (CBV) 4.4 versus 4.3
      mL/100 g, CNR 1.59 versus 1.64 and P/I index 0.74 versus 0.73, respectively) and
      subjective diagnostic IQ (mean Likert scale 1.42 versus 1.49, respectively). The
      overall IQ in half-dose with high IR level was scored lower in 26-31%. Half-dose
      with FBP and with the middle IR level were inferior to standard dose with FBP.
      CONCLUSION: With the use of IR in CTP imaging it is possible to examine patients
      with a half dose without significantly altering the objective and diagnostic IQ.
      The standard dose with FBP is still preferable in terms of subjective overall IQ
      in about one quarter of patients. KEY POINTS: * Computed tomography perfusion
      (CTP) is increasingly important in ischaemia imaging. * Radiation exposure of CTP
      is a drawback. * Iterative reconstruction (IR) allows reduction of radiation dose
      in unenhanced head CT. * CTP IR enables 50% dose reduction without altering
      objective and diagnostic quality.

PMID- 24126644
TI  - Hospital report cards for hospital-acquired pressure ulcers: how good are the
      grades?
AB  - BACKGROUND: Value-based purchasing programs use administrative data to compare
      hospitals by rates of hospital-acquired pressure ulcers (HAPUs) for public
      reporting and financial penalties. However, validation of these data is lacking.
      OBJECTIVE: To assess the validity of the administrative data used to generate
      HAPU rates by comparing the rates generated from these data with those generated
      from surveillance data. DESIGN: Retrospective analysis of 2 million all-payer
      administrative records from 448 California hospitals and quarterly hospitalwide
      surveillance data from 213 hospitals from the Collaborative Alliance for Nursing
      Outcomes (as publicly reported on the CalHospitalCompare Web site). SETTING: 196
      acute care hospitals with at least 6 months of available administrative and
      surveillance data. PATIENTS: Nonobstetric adults discharged in 2009.
      MEASUREMENTS: Hospital-specific HAPU rates were computed as the percentage of
      discharged adults (from administrative data) or examined adults (from
      surveillance data) with at least 1 stage II or greater HAPU (HAPU2+).
      Categorization of hospital performance based on administrative data was compared
      with the grade assigned when surveillance data were used. RESULTS: When
      administrative data were used, the mean hospital-specific HAPU2+ rate was 0.15%
      (95% CI, 0.13% to 0.17%); when surveillance data were used, the rate was 2.0%
      (CI, 1.8% to 2.2%). Among the 49 hospitals with HAPU2+ rates in the highest
      (worst) quartile from administrative data, use of the surveillance data set
      resulted in performance grades of "superior" for 3 of these hospitals, "above
      average" for 14, "average" for 15, and "below average" for 17. LIMITATION: Data
      are from 1 state and 1 year. CONCLUSION: Hospital performance scores generated
      from HAPU2+ rates varied considerably according to whether administrative or
      surveillance data were used, suggesting that administrative data may not be
      appropriate for comparing hospitals. PRIMARY FUNDING SOURCE: Agency for
      Healthcare Research and Quality.

PMID- 24126645
TI  - Prevalence of unruptured cerebral aneurysms in Chinese adults aged 35 to 75
      years: a cross-sectional study.
AB  - BACKGROUND: The reported prevalence of unruptured cerebral aneurysms (UCAs)
      varies widely. OBJECTIVE: To measure the prevalence of UCAs by using 3
      dimensional time-of-flight magnetic resonance angiography in adults aged 35 to 75
      years. DESIGN: Cross-sectional study done between June 2007 and June 2011.
      SETTING: Two communities chosen at random from 2 districts (1 urban and 1
      suburban) in Shanghai, China. PARTICIPANTS: 4813 adults aged 35 to 75 years.
      MEASUREMENTS: Three-dimensional time-of-flight magnetic resonance angiography,
      interpreted by 3 observers blinded to the participants' information, was used to
      identify the location and size of UCAs and to estimate the overall, age-specific,
      and sex-specific prevalence. RESULTS: 369 UCAs were found in 336 participants
      (130 men and 206 women); 4477 participants had no evidence of UCAs. The
      prevalence was 7.0% overall (95% CI, 6.3% to 7.7%), with 5.5% for men (CI, 4.6%
      to 6.4%) and 8.4% for women (CI, 7.3% to 9.5%). The overall prevalence of UCAs
      was higher in women than in men (P < 0.001) and peaked at ages 55 to 64 years in
      men and women. The UCAs were mostly located in the internal carotid artery (81%),
      and 90.2% had a maximum diameter less than 5 mm. Mean diameter was larger in
      women than in men (3.7 mm vs. 3.2 mm; P < 0.009). LIMITATION: Participants were
      from 2 communities selected from 2 districts in Shanghai, and adults older than
      75 years were not studied. CONCLUSION: The overall prevalence of UCAs was 7.0% in
      Chinese adults aged 35 to 75 years, and most lesions had a diameter less than 5
      mm. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

PMID- 24126646
TI  - Albumin dialysis with a noncell artificial liver support device in patients with
      acute liver failure: a randomized, controlled trial.
AB  - BACKGROUND: Albumin dialysis with the Molecular Adsorbent Recirculating System
      (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be
      beneficial in acute liver failure (ALF). OBJECTIVE: To determine whether MARS
      improves survival in ALF. DESIGN: Randomized, controlled trial.
      (ClinicalTrials.gov: NCT00224705). SETTING: 16 French liver transplantation
      centers. PATIENTS: 102 patients with ALF. INTERVENTION: Conventional treatment (n
      = 49) or MARS with conventional treatment (n = 53), stratified according to
      whether paracetamol caused ALF. MEASUREMENTS: 6-month survival and secondary end
      points, including adverse events. RESULTS: 102 patients (mean age, 40.4 years
      [SD, 13]) were in the modified intention-to-treat (mITT) population. The per
      protocol analysis (49 conventional, 39 MARS) included patients with at least 1
      session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8%
      to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P
      = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional
      treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol
      population. In patients with paracetamol-related ALF, the 6-month survival rate
      was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1%
      to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients
      had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non
      paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ
      between groups. LIMITATION: The short delay from randomization to liver
      transplantation (median, 16.2 hours) precludes definitive efficacy or safety
      evaluations. CONCLUSION: This randomized trial of MARS in patients with ALF was
      unable to provide definitive efficacy or safety conclusions because many patients
      had transplantation before administration of the intervention. Acute liver
      failure not caused by paracetamol was associated with greater 6-month patient
      survival. PRIMARY FUNDING SOURCE: Assistance Publique-Hopitaux de Paris.

PMID- 24126647
TI  - Advanced wound care therapies for nonhealing diabetic, venous, and arterial
      ulcers: a systematic review.
AB  - BACKGROUND: Nonhealing ulcers affect patient quality of life and impose a
      substantial financial burden on the health care system. PURPOSE: To
      systematically evaluate benefits and harms of advanced wound care therapies for
      nonhealing diabetic, venous, and arterial ulcers. DATA SOURCES: MEDLINE (1995 to
      June 2013), the Cochrane Library, and reference lists. STUDY SELECTION: English
      language randomized trials reporting ulcer healing or time to complete healing in
      adults with nonhealing ulcers treated with advanced therapies. DATA EXTRACTION:
      Study characteristics, outcomes, adverse events, study quality, and strength of
      evidence were extracted by trained researchers and confirmed by the principal
      investigator. DATA SYNTHESIS: For diabetic ulcers, 35 trials (9 therapies) met
      eligibility criteria. There was moderate-strength evidence for improved healing
      with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to
      2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared
      with standard care and low-strength evidence for platelet-derived growth factors
      and silver cream compared with standard care. For venous ulcers, 20 trials (9
      therapies) met eligibility criteria. There was moderate-strength evidence for
      improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared
      with standard care and low-strength evidence for biological dressing and a
      biological skin equivalent compared with standard care. One small trial of
      arterial ulcers reported improved healing with a biological skin equivalent
      compared with standard care. Overall, strength of evidence was low for ulcer
      healing and low or insufficient for time to complete healing. LIMITATIONS: Only
      studies of products approved by the U.S. Food and Drug Administration were
      reviewed. Studies were predominantly of fair or poor quality. Few trials compared
      2 advanced therapies. CONCLUSION: Compared with standard care, some advanced
      wound care therapies may improve the proportion of ulcers healed and reduce time
      to healing, although evidence is limited. PRIMARY FUNDING SOURCE: Department of
      Veterans Affairs, Veterans Health Administration, Office of Research and
      Development, Quality Enhancement Research Initiative.

PMID- 24126648
TI  - Lifestyle interventions for patients with and at risk for type 2 diabetes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The effect of multifaceted lifestyle interventions on clinically
      oriented outcomes across a spectrum of metabolic risk factors and abnormal
      glucose is unclear. PURPOSE: To systematically review the effectiveness of
      lifestyle interventions on minimizing progression to diabetes in high-risk
      patients or progression to clinical outcomes (such as cardiovascular disease and
      death) in patients with type 2 diabetes. DATA SOURCES: 5 electronic databases
      (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION: Two
      reviewers independently identified randomized, controlled trials of lifestyle
      interventions (>=3 months' duration) that included exercise, diet, and at least 1
      other component; the comparator was standard care. DATA EXTRACTION: One reviewer
      extracted and a second verified data. Two reviewers independently assessed
      methodological quality. DATA SYNTHESIS: Nine randomized, controlled trials with
      patients who were at risk for diabetes and 11 with patients who had diabetes were
      included. Seven studies reported that lifestyle interventions decreased the risk
      for diabetes from the end of intervention up to 10 years after it. In patients
      with diabetes, 2 randomized, controlled trials (which included pharmacotherapy)
      reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to
      1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to
      pool. One trial reported improvement in microvascular outcomes at 13-year follow
      up. LIMITATION: Most trials focused on surrogate measures (such as weight change,
      blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION:
      Comprehensive lifestyle interventions effectively decrease the incidence of type
      2 diabetes in high-risk patients. In patients who already have type 2 diabetes,
      there is no evidence of reduced all-cause mortality and insufficient evidence to
      suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING
      SOURCE: Agency for Healthcare Research and Quality.

PMID- 24126649
TI  - Corpulence and correspondence: President William H. Taft and the medical
      management of obesity.
AB  - This article analyzes the letters exchanged as part of the clinical weight
      management of President William H. Taft, one of the first public figures in U.S.
      history to be defined popularly in terms of his pathologic obesity. In 1905, Taft
      hired Dr. Nathaniel E. Yorke-Davies, an English diet expert, to supervise a
      weight-loss plan. Taft corresponded extensively with Yorke-Davies over the next
      10 years, receiving and responding to courses of treatment via post. This
      correspondence is one of the few archival collections documenting physician and
      patient perspectives on the treatment of obesity, and it took place at the
      precise moment when obesity began to be framed as both a serious and medically
      manageable condition. This intimate clinical history of the 27th president and
      10th chief justice of the Supreme Court offers a unique opportunity to examine in
      detail the history of the obesity experience in the United States, and it sheds
      light on the almost-timeless challenges of creating and maintaining long-term
      treatment courses for conditions like obesity.

PMID- 24126650
TI  - Pressure ulcers: even the grading of facilities fails.

PMID- 24126651
TI  - Super-Storm Sandy and the human element.

PMID- 24126652
TI  - Observation versus initial treatment for prostate cancer.

PMID- 24126653
TI  - Observation versus initial treatment for prostate cancer.

PMID- 24126654
TI  - Statin toxicity from macrolide antibiotic coprescription.

PMID- 24126655
TI  - Statin toxicity from macrolide antibiotic coprescription.

PMID- 24126656
TI  - What is our plan for acute unscheduled care?

PMID- 24126657
TI  - What is our plan for acute unscheduled care?

PMID- 24126658
TI  - Summaries for patients. How common are unruptured brain aneurysms in adults?

PMID- 24126659
TI  - ACP Journal Club. Mandibular advancement device and CPAP did not differ for
      health outcomes in obstructive sleep apnea.

PMID- 24126660
TI  - ACP Journal Club. Review: Approved and some off-label preventive drugs reduce
      migraine frequency in episodic migraine.

PMID- 24126661
TI  - ACP Journal Club. Review: NSAIDs increase GI and CV events; coxibs increase
      mortality.

PMID- 24126662
TI  - ACP Journal Club. Review: Yoga reduces low back pain and back-specific
      disability.

PMID- 24126663
TI  - ACP Journal Club. Apixaban was noninferior to enoxaparin plus warfarin in
      patients with acute venous thromboembolism.

PMID- 24126664
TI  - ACP Journal Club. Review: Bariatric surgery improves weight and glycemia in
      nonmorbidly obese adults with diabetes.

PMID- 24126665
TI  - ACP Journal Club. A lifestyle intervention did not reduce cardiovascular outcomes
      in overweight or obese patients with type 2 diabetes.

PMID- 24126666
TI  - ACP Journal Club. Adding clopidogrel to aspirin after TIA or minor ischemic
      stroke reduced stroke without increasing bleeding.

PMID- 24126667
TI  - ACP Journal Club. In adults with acute ICH, intensive BP management did not
      reduce death or major disability.

PMID- 24126668
TI  - ACP Journal Club. Review: Probiotics prevent C. difficile-associated diarrhea in
      patients using antibiotics.

PMID- 24126669
TI  - ACP Journal Club. Adding rifaximin to lactulose increased reversal and decreased
      mortality in hepatic encephalopathy.

PMID- 24126670
TI  - ACP Journal Club. Review: Antibiotic prophylaxis on removal of urinary catheters
      reduces symptomatic urinary tract infections.

PMID- 24126671
TI  - Winter wheat cells subjected to freezing temperature undergo death process with
      features of programmed cell death.
AB  - Programmed cell death is a process defined as genetically regulated self
      destruction or cell suicide. It can be activated by different internal and
      external factors, but few studies have investigated whether this process occurs
      under cold and freezing temperatures. In this study, a freezing treatment (-8 
      degrees C for 6 h) induced cell death with features of programmed cell death in
      suspension cultures of winter wheat (Triticum aestivum L.). This process occurred
      for 10 days after cold exposure. The death of cells in culture was slow and
      prolonged, and was accompanied by protoplast shrinkage, DNA fragmentation, and an
      increase in the level of reactive oxygen species. Other changes observed after
      the freezing treatment included an increase in the respiration rate, changes in
      mitochondrial transmembrane potential (?Psi m ), and the release of cytochrome c
      from mitochondria into the cytosol. These findings indicated that mitochondria
      are involved in the cell death process that occurs after a freezing treatment in
      cells of winter wheat. 

PMID- 24126672
TI  - Critical illness in homeless persons is poorly studied: a systematic review of
      the literature.

PMID- 24126673
TI  - Raising positive end-expiratory pressures in ARDS to achieve a positive
      transpulmonary pressure does not cause hemodynamic compromise.

PMID- 24126674
TI  - Effects of adaptive degrees of trust on coevolution of quantum strategies on
      scale-free networks.
AB  - We study the impact of adaptive degrees of trust on the evolution of cooperation
      in the quantum prisoner's dilemma game. In addition to the strategies, links
      between players are also subject to evolution. Starting with a scale-free
      interaction network, players adjust trust towards their neighbors based on
      received payoffs. The latter governs the strategy adoption process, while trust
      governs the rewiring of links. As soon as the degree of trust towards a neighbor
      drops to zero, the link is rewired to another randomly chosen player within the
      network. We find that for small temptations to defect cooperators always
      dominate, while for intermediate and strong temptations a single quantum strategy
      is able to outperform all other strategies. In general, reciprocal trust remains
      within close relationships and favors the dominance of a single strategy. Due to
      coevolution, the power-law degree distributions transform to Poisson
      distributions. 

PMID- 24126675
TI  - A Novel Ratiometric Fluorescent Mercury Probe Based on Deprotonation-ICT
      Mechanism.
AB  - A new NBD-rhodamine dye (1) was developed as a colorimetric and ratiometric
      fluorescent chemosensor for Hg(2+) with good selectivity in aqueous ethanol
      solutions under neutral to basic conditions. Sensor 1 showed absorption at 468 nm
      and a weak emission at 529 nm (phi F  = 0.063) in ethanol/aqueous tris buffer
      (9:1, v/v) of pH 9.17 solution. Bathochromic shifts in both absorption (492 nm)
      and fluorescence spectra (569 nm, phi F  = 0.129), respectively upon addition of
      2 equiv. of Hg(2+) were observed. The ring-opening reaction of the spirolactam
      form to the corresponding xanthene form was not found. The interaction of Hg(2+)
      with chemosensor 1 resulted in the deprotonation of the secondary amine
      conjugated to the NBD component so that the electron-donating ability of the N
      atom was enhanced. Deprotonation-ICT mechanism of secondary amines was suggested
      for the ratiometric fluorescent chemosensing for Hg(2+). 

PMID- 24126676
TI  - Differential effectiveness of placebo treatments: a systematic review of migraine
      prophylaxis.
AB  - IMPORTANCE: When analyzing results of randomized clinical trials, the treatment
      with the greatest specific effect compared with its placebo control is considered
      to be the most effective one. Although systematic variations of improvements in
      placebo control groups would have important implications for the interpretation
      of placebo-controlled trials, the knowledge base on the subject is weak.
      OBJECTIVE: To investigate whether different types of placebo treatments are
      associated with different responses using the studies of migraine prophylaxis for
      this analysis. DESIGN, SETTING, AND PARTICIPANTS: We searched relevant sources
      through February 2012 and contacted the authors to identify randomized clinical
      trials on the prophylaxis of migraine with an observation period of at least 8
      weeks after randomization that compared an experimental treatment with a placebo
      control group. We calculated pooled random-effects estimates according to the
      type of placebo for the proportions of treatment response. We performed meta
      regression analyses to identify sources of heterogeneity. In a network meta
      analysis, direct and indirect comparisons within and across trials were combined.
      Additional analyses were performed for continuous outcomes. EXPOSURE: Active
      migraine treatment and the placebo control conditions. MAIN OUTCOMES AND
      MEASURES: Proportion of treatment responders, defined as having an attack
      frequency reduction of at least 50%. Other available outcomes in order of
      preference included a reduction of 50% or greater in migraine days, the number of
      headache days, or headache score or a significant improvement as assessed by the
      patients or their physicians. RESULTS: Of the 102 eligible trials, 23 could not
      be included in the meta-analyses owing to insufficient data. Sham acupuncture
      (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37
      0.77]) were associated with a more pronounced reduction of migraine frequency
      than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only
      significant predictors of response in placebo groups in multivariable analyses (P
      = .005 and P = .001, respectively). Network meta-analysis confirmed that more
      patients reported response in sham acupuncture groups than in oral
      pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]).
      Corresponding analyses for continuous outcomes showed similar findings.
      CONCLUSIONS AND RELEVANCE: Sham acupuncture and sham surgery are associated with
      higher responder ratios than oral pharmacological placebos. Clinicians who treat
      patients with migraine should be aware that a relevant part of the overall effect
      they observe in practice might be due to nonspecific effects and that the size of
      such effects might differ between treatment modalities.

PMID- 24126677
TI  - Effects of Japanese herbal medicine Sairei-to on murine experimental autoimmune
      uveitis.
AB  - PURPOSE: It has been suggested thatSairei-to (TJ114), a traditional Japanese
      herbal medicine, has immunomodulatory activities. To evaluate the effects of
      TJ114 on uveitis, we examined the effectiveness of oral administration in a
      murine model of experimental autoimmune uveitis (EAU). METHODS: Murine EAU was
      induced by subcutaneous injection of human inter-photoreceptor retinoid-binding
      protein (IRBP) peptide mixed with complete Freund's adjuvant. In the TJ114
      treated group, 2 g/kg was administrated orally from 0 to 20 days after
      immunization. Clinical scoring, histopathological scoring of EAU, cell
      proliferation, cytokine assessment, and adoptive transfer experiment of splenic T
      cells into naive mice were performed. RESULTS: EAU development occurred in 32 of
      38 mice (86 %) in the untreated group and 12 of 33 (36 %) in the TJ114-treated
      group. The clinical scores for EAU in the vehicle-treated and TJ114-treated
      groups were 1.56 +/- 1.65 and 0.59 +/- 0.63 respectively, at 14 days after
      immunization (p < 0.01, Mann-Whitney U-test), and 2.26 +/- 1.56 and 0.75 +/- 1.31
      respectively at 21 days (p < 0.001, Mann-Whitney U-test), while the
      histopathological scores at 21 days were 1.47 +/- 1.42 and 0.54 +/- 0.84
      respectively (p < 0.01, Mann-Whitney U-test). Interferon (IFN)-gamma and tumor
      necrosis factor (TNF)-alpha production by cervical lymph node cells obtained from
      the TJ114-treated group were significantly reduced as compared with those from
      the vehicle-treated group (p < 0.01, Student's unpaired t-test). Moreover, the
      levels of C-C motif chemokine 2 (CCL2) and IFN-gamma were significantly reduced
      in splenocytes of TJ114-treated mice as compared with the vehicle-treated group
      (p < 0.01, Student's unpaired t-test). Mice that received adoptive transfer of
      splenic T cells from TJ114-treated EAU mice caused significantly lower severity
      of EAU compared to those that received from vehicle-treated EAU mice. CONCLUSION:
      Oral administration of TJ114 has an inhibitory effect on a murine model of EAU,
      possibly via reduction in cytokine production by helper type-1 T cells.

PMID- 24126678
TI  - Clinical and histological features of epiretinal membrane after diabetic
      vitrectomy.
AB  - PURPOSE: To investigate the clinical, histopathological, and surgical features of
      the epiretinal membrane (ERM) after diabetic vitrectomy (DV). METHODS: From
      August 2007 to January 2010, clinical charts of consecutive proliferative
      diabetic retinopathy (PDR) cases with significant post-DV ERM, defined as
      thickened membrane causing macular distortion and vision decrease, were enrolled
      as the study group; PDR cases without post-DV ERM in 24 months follow-up served
      as the control group. Factors associated with post-DV ERM formation,
      morphological and visual changes before and after ERM surgery, and
      histopathological features were analyzed. RESULTS: Sixteen eyes were in the ERM
      group, while 60 eyes were in the control group. Active PDR (p < 0.001),
      fibrovascular proliferation (FVP) grade (p = 0.001), post-DV hemorrhage (p =
      0.012), and residual fibrovascular stump (p = 0.002) were factors significantly
      associated with post-DV ERM. Most membranes (87.5 %) developed within 12 months,
      were widespread beyond the arcade (81.3 %), and connected with retinal vessels
      (87.5 %). After surgery, significant VA improvement was achieved. ERM recurrence
      was noted in six eyes (37.5 %). Histopathological examinations of ERMs in six
      cases showed abundant collagen fibers with epithelial cells. Immunohistochemical
      staining with CD 34 demonstrated the presence of vascular endothelium in two of
      the six specimens. CONCLUSION: The post-DV ERM is a complex tissue with variable
      vascularity that often presents with widespread distribution, rapid progression,
      and causes macular distortion. Associated risk factors include active PDR, high
      FVP grade, post-DV hemorrhage, and residual fibrovascular stumps. Membrane
      removal surgery may be beneficial in selected cases, but recurrence is not
      uncommon.

PMID- 24126679
TI  - Mean platelet volume measurement protocol should be standardized for diabetic
      retinopathy.

PMID- 24126680
TI  - Optical near-field excitation at commercial scanning probe microscopy tips: a
      theoretical and experimental investigation.
AB  - A systematic study of the influence of the excitation angle, the light
      polarization and the coating thickness of commercial SPM tips on the field
      enhancement in an apertureless scanning near-field optical microscope is
      presented. A new method to optimize the alignment of the electric field vector
      along the major tip axis by measuring the resonance frequency was developed. The
      simulations were performed with a MNPBEM toolbox based on the Boundary Element
      Method (BEM). The influence of the coating thickness was investigated for the
      first time. Coatings below 40 nm showed a drastic influence both on the resonance
      wavelength and the enhancement. A shift to higher angles of incidence for the
      maximum enhancement could be observed for greater tip radii. 

PMID- 24126681
TI  - Identification and characterization of a defective CYP3A4 genotype in a kidney
      transplant patient with severely diminished tacrolimus clearance.
AB  - Cytochrome P450 3A4 (CYP3A4) is a major drug-metabolizing enzyme that is widely
      investigated. So far, no homozygous inactive variant has been described. We
      report on a 19-year-old kidney transplant patient suffering from Alport syndrome,
      who experienced unexpected high tacrolimus plasma trough levels during
      immunosuppressant therapy. Because nonadherence, liver failure, or drug-drug
      interactions could be excluded, we hypothesized a diminished metabolism of the
      drug caused by mutations in the main detoxification enzyme, CYP3A4. Exome
      sequencing revealed a novel single-nucleotide polymorphism (c.802C>T) resulting
      in a premature stop codon in CYP3A4 exon 5. Accordingly, no CYP3A4 protein could
      be detected in kidney biopsy tissue, and there was lack of expression in HepG2
      cells transiently transfected with the mutated CYP3A4. In addition, the patient
      harbored inactive CYP3A5*3, resulting in loss of function of the entire CYP3A
      locus, explaining the deteriorated tacrolimus clearance. This is, to our
      knowledge, the first case of a complete failure of CYP3A4 in humans. 

PMID- 24126682
TI  - Novel therapeutic approaches for hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people
      worldwide and is often complicated by cirrhosis and hepatocellular carcinoma.
      Morbidity and mortality are decreased with the successful treatment of chronic
      HCV infection. The current standard of care in the treatment for genotype 1
      chronic HCV is pegylated interferon (IFN)-alfa, termed PEG, and ribavirin (RBV)
      in conjunction with a protease inhibitor, either telaprevir or boceprevir, which
      results in 67-75% sustained viral response rates. Increased understanding of the
      HCV has allowed further development of new direct-acting antiviral (DAA) agents
      against the HCV and has also allowed the development of IFN-free oral treatment
      regimens. We anticipate the approval in late 2013 of the first nucleotide
      polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination
      with a 12-week regimen of PEG+RBV for genotypes 1, 4, 5, and 6. Most of the
      promising new DAA regimens are discussed herein.

PMID- 24126683
TI  - Parthenolide induces superoxide anion production by stimulating EGF receptor in
      MDA-MB-231 breast cancer cells.
AB  - The sesquiterpene lactone parthenolide (PN) has recently attracted considerable
      attention because of its anti-microbial, anti-inflammatory and anticancer
      effects. However, the mechanism of its cytotoxic action on tumor cells remains
      scarcely defined. We recently provided evidence that the effect exerted by PN in
      MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen
      species (ROS). The present study shows that PN promoted the phosphorylation of
      EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1
      h of incubation with 25 uM PN and reached a peak at 8-16 h. This effect seemed to
      be a consequence of ROS production, because N-acetylcysteine (NAC), a powerful
      ROS scavenger, prevented the increment of phospho-EGFR levels. In addition
      fluorescence analyses performed using dihydroethidium demonstrated that PN
      stimulated the production of superoxide anion already at 2-3 h of incubation and
      the effect further increased prolonging the time of treatment, reaching a peak at
      8-16 h. Superoxide anion production was markedly hampered by apocynin, a well
      known NADPH oxidase (NOX) inhibitor, suggesting that the effect was dependent on
      NOX activity. The finding that AG1478, an EGFR kinase inhibitor, substantially
      blocked both EGFR phosphorylation and superoxide anion production strongly
      suggested that phosphorylation of EGFR can be responsible for the activation of
      NOX with the consequent production of superoxide anion. Therefore, EGFR
      phosphorylation can exert a key role in the production of superoxide anion and
      ROS induced by PN in MDA-MB-231 cells.

PMID- 24126684
TI  - Competition between antiferromagnetism and ferromagnetism in Sr2RuO4 probed by Mn
      and Co doping.
AB  - Spin-triplet superconductivity in Sr2RuO4 has attracted enormous interest. Like
      other unconventional superconductors, superconductivity in Sr2RuO4 is in close
      proximity to magnetic instability. Undoped Sr2RuO4 exhibits incommensurate
      antiferromagnetic (AFM) fluctuations, which can evolve into static, short-range
      AFM order via Ti doping. Moreover, weak ferromagnetic (FM) coupling in Sr2RuO4
      has also been suggested by NMR/neutron scattering experiments and studies on Ca2
      xSrxRuO4 and Sr2-yLayRuO4, implying orbital dependent magnetism. We report bulk
      static, short-range FM order in Sr2RuO4 triggered by <2% Co doping, showing
      superconductivity in Sr2RuO4 is much closer to FM instability than previously
      reported in Ca2-xSrxRuO4. We also find Mn doping can effectively establish
      incommensurate AFM order, with TN ~ 50 K for 3% Mn doping. These new results
      place Sr2RuO4 in a unique situation where superconductivity lies directly on the
      borderline of two distinct magnetic states, highlighting the important role of
      competing magnetic fluctuations in determining superconducting properties of
      Sr2RuO4. 

PMID- 24126685
TI  - The quality of supportive cancer care in the veterans affairs health system and
      targets for improvement.
AB  - IMPORTANCE: Characterizing the quality of supportive cancer care can guide
      quality improvement. OBJECTIVE: To evaluate nonhospice supportive cancer care
      comprehensively in a national sample of veterans. DESIGN, SETTING, AND
      PARTICIPANTS: Using a retrospective cohort study design, we measured evidence
      based cancer care processes using previously validated indicators of care quality
      in patients with advanced cancer, addressing pain, nonpain symptoms, and
      information and care planning among 719 veterans with a 2008 Veterans Affairs
      Central Cancer Registry diagnosis of stage IV colorectal (37.0%), pancreatic
      (29.8%), or lung (33.2%) cancer. MAIN OUTCOMES AND MEASURES: We abstracted
      medical records from diagnosis for 3 years or until death among eligible veterans
      (lived >= 30 days following diagnosis with >= 1 Veterans Affairs hospitalization
      or >= 2 Veterans Affairs outpatient visits). Each indicator identified a clinical
      scenario and an appropriate action. For each indicator for which a veteran was
      eligible, we determined whether appropriate care was provided. We also determined
      patient-level quality overall and by pain, nonpain symptoms, and information and
      care planning domains. RESULTS: Most veterans were older (mean age, 66.2 years),
      male (97.2%), and white (74.3%). Eighty-five percent received both inpatient and
      outpatient care, and 92.5% died. Overall, the 719 veterans triggered a mean of
      11.7 quality indicators (range, 1-22) and received a mean 49.5% of appropriate
      care. Notable gaps in care were that inpatient pain screening was common (96.5%)
      but lacking for outpatients (58.1%). With opioids, bowel prophylaxis occurred for
      only 52.2% of outpatients and 70.5% of inpatients. Few patients had a timely
      dyspnea evaluation (15.8%) or treatment (10.8%). Outpatient assessment of fatigue
      occurred for 31.3%. Of patients at high risk for diarrhea from chemotherapy,
      24.2% were offered appropriate antidiarrheals. Only 17.7% of veterans had goals
      of care addressed in the month after a diagnosis of advanced cancer, and 63.7%
      had timely discussion of goals following intensive care unit admission. Most
      decedents (86.4%) were referred to palliative care or hospice before death.
      Single- vs multiple-fraction radiotherapy should have been considered in 28
      veterans with bone metastasis, but none were offered this option. CONCLUSIONS AND
      RELEVANCE: These care gaps reflect important targets for improving the patient
      and family experience of cancer care.

PMID- 24126686
TI  - Antipsychotic prescription filling in patients with schizophrenia or
      schizoaffective disorder.
AB  - OBJECTIVE: Assessment of factors influencing antipsychotic prescription fills in
      the early phase of schizophrenia or schizoaffective disorder. METHODS: We used
      the Swedish Patient Register to identify patients younger than 45 years with a
      first hospitalization for schizophrenia or schizoaffective disorder between 2006
      and 2007 (904 patients). Data on medication were obtained from the Prescribed
      Drug Register. Filling a prescription of an antipsychotic drug after discharge
      was used to estimate medication adherence. In Cox regression models, we studied
      sex, country of birth, metropolitan residence, educational level, age, duration
      of hospitalization, history of substance use disorder, and previous use of
      antipsychotic drugs as predictors for antipsychotic fills. RESULTS: Among all
      patients, 53.1% (95% confidence interval [CI] 49.9%-56.4%) had filled an
      antipsychotic prescription within 1 week from discharge. After 6 months, the
      proportion had increased to 80.2% (95% CI, 77.4%-82.8%) with no further increase
      thereafter. Prescription filling of an antipsychotic drug was primarily
      associated with antipsychotic use before the hospitalization (hazard ratio, 1.64;
      95% CI, 1.33-2.03; for patients with access to antipsychotic drugs at admission
      compared with no previous use) and with longer hospitalization (hazard ratio,
      1.60; 95% CI, 1.27-2.02 for 15-28 days compared with shorter hospitalization).
      CONCLUSIONS: Among patients who filled a prescription of an antipsychotic drug
      after discharge, the majority did so within 1 week. Previous adherent use of
      antipsychotic drugs and longer hospitalization may be predictors of primary
      adherence to antipsychotic drug treatment in schizophrenia or schizoaffective
      disorder.

PMID- 24126688
TI  - Spectrum and frequencies of mutations in the MFN2 gene and its phenotypical
      expression in Czech hereditary motor and sensory neuropathy type II patients.
AB  - The axonal type of Charcot-Marie-Tooth (CMT) disorders is genetically
      heterogeneous, therefore the causal mutation is unlikely to be observed, even in
      clinically well characterized patients. Mitofusin-2 (MFN2) gene mutations are the
      most frequent cause of axonal CMT disorders in a number of populations. There are
      two phenotypes; early onset, which is severe and late onset, which is a milder
      phenotype. A cohort of 139 unrelated Czech patients with axonal neuropathy was
      selected for sequencing and multiplex ligation-dependent probe amplification
      analysis (MLPA) testing of the MFN2 gene. A total of 11 MFN2 mutations were
      detected, with eight pathogenic mutations and three potentially rare benign
      polymorphisms. MLPA testing in 64 unrelated patients did not detect any exon
      duplication or deletion. The frequency of the pathogenic mutations detected in
      Czech hereditary motor and sensory neuropathy type II (HMSN II) patients was
      7.2%. Early onset was more frequent among pathogenic mutation cases. Therefore we
      propose to examine the MFN2 gene mainly in patients with early and severe axonal
      CMT.

PMID- 24126689
TI  - High-intensity pulse light sintering of silver nanowire transparent films on
      polymer substrates: the effect of the thermal properties of substrates on the
      performance of silver films.
AB  - Silver nanowire (AgNW) films with a random mesh structure have attracted
      considerable attention as high-performance flexible transparent electrodes that
      can replace the expensive and brittle ITO-sputtered films widely used in
      displays, touch screens, and solar cells. Methods such as heating, pressure
      treatment, and light treatment are usually used to obtain an optically
      transparent and electrically conductive film comparable to those of commercial
      ITO. However, the adhesion between the AgNW film and the substrate is so weak
      that other overcoatings or extra treatments are necessary. Here, a high-intensity
      pulsed light (HIPL) sintering technique was developed to rapidly and simply
      sinter the AgNW film and thus achieve strong adhesion and even high conductivity
      on these flexible polymer substrates which will be widely applied to the printing
      of electronic devices. The conductivity of the AgNW film closely depended on the
      thermal performance of substrates, and the adhesion was determined by the soft
      state of the substrate surface originating from the glass transition or melting
      of substrates with light intensity. The rapid sintering technique can be
      popularized to fabricate new devices on these polymer substrates by considering
      the thermal properties of the substrate to improve the performance of devices. 

PMID- 24126690
TI  - The patient with a history of congenital heart disease who is to undergo
      ambulatory surgery.
AB  - PURPOSE OF REVIEW: There is a strong pressure to widen the indications of
      ambulatory anaesthesia in children. Making a decision concerning a child with a
      history of cardiac disease is often difficult. The aim of this review is to give
      practical recommendations to help the anaesthesiologist recognize potentially
      dangerous situations in children with a history of cardiac disease. RECENT
      FINDINGS: The anaesthetic care of a child with a history of heart disease
      presenting for an ambulatory procedure includes three steps: understanding the
      pathophysiology of the child's current haemodynamic status, checking whether
      he/she is actually eligible for outpatient anaesthesia and planning the safest
      anaesthetic plan, accordingly. The concept of congenital heart disease nowadays
      includes not only congenital heart defects but also congenital dysrythmias such
      as congenital long QT and Brugada syndromes, and acquired lesions such as
      sequellae of Kawasaki disease. Children with a partially corrected or palliated
      cardiac defect tolerate poorly hypovolaemia, systemic hypotension and hypoxaemia.
      They should thus not undergo on an ambulatory basis procedures during or after
      which such problems can occur. Moreover, postoperative analgesia should be
      carefully planned with the parents. SUMMARY: A child whose cardiac disease has
      been corrected, who is developing well, has no exercise restriction and undergoes
      regular cardiologic follow-up does not present more risks than any normal
      American Society of Anesthesiologists physical status 1-2 child. Any other
      situation requires close communication with the child's paediatric cardiologist
      to evaluate the risks of both anaesthesia and outpatient care, and make an
      individualized decision accordingly.

PMID- 24126691
TI  - Beyond the caudal: truncal blocks an alternative option for analgesia in
      pediatric surgical patients.
AB  - PURPOSE OF REVIEW: To discuss and compare the more commonly used truncal blocks
      with neuraxial techniques in children undergoing a variety of thoracic, abdominal
      and urological procedures. RECENT FINDINGS: Owing to the advent of
      ultrasonography and its increasing use in regional anesthesia, there has been a
      renewed interest in implementing these techniques in children for intraoperative
      and postoperative pain management. SUMMARY: The use of regional anesthesia
      particularly with ultrasound guidance is an integral part of pain management
      during the intraoperative and postoperative period in children who undergo
      surgery. Its use is essential in improving patient pain control and overall
      satisfaction as well as decreasing hospital stay and reducing hospital admission
      after surgery. Truncal blocks serve as an excellent alternative to neuraxial
      blockade, in patients who have a contraindication to neuraxial blockade, patients
      undergoing a unilateral procedure and those in an outpatient ambulatory setting
      undergoing routine procedures, wherein the adverse effects of neuraxial blockade
      such as motor weakness, difficulty ambulating, urinary retention, increased
      nausea and vomiting, may delay same day discharge.

PMID- 24126692
TI  - The changing landscape of anesthesia education: is Flipped Classroom the answer?
AB  - PURPOSE OF REVIEW: Educators in the specialty of anesthesiology are facing a
      number of challenges. A new generation of residents are entering the specialty
      and they have unique learning styles and expectations. The new duty hour
      regulations also encroach on the time available to the residents for education.
      In the last decade, a number of models for teaching and learning have been
      proposed to tackle these issues. RECENT FINDINGS: Recent research has looked at
      learning gains and acceptability of online material in medical education as well
      as specific models that can be implemented to address the challenges. SUMMARY:
      The 'Flipped Classroom' model seems to combine the best of both worlds. It allows
      the learner to assimilate basic information (lower order cognitive skills) from
      material that is placed online, allowing asynchronous learning. It frees up the
      teacher to use the face-to-face interaction time in the operating room and
      classroom for training the student in advanced concepts (higher order cognitive
      skills). This model allows efficient and effective use of time and technology,
      but involves the redesign of how in person time between faculty and residents are
      spent, along with the faculty development to effectively engage this new type of
      curriculum.

PMID- 24126693
TI  - It is time to broaden our vision in medical education.

PMID- 24126694
TI  - Lanthanum carbonate stimulates bone formation in a rat model of renal
      insufficiency with low bone turnover.
AB  - Control of phosphate is important in the management of chronic kidney disease
      with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non
      calcium phosphate-binding agent, has recently been introduced; however, it
      remains to be determined whether it has any beneficial or deleterious effect on
      bone remodeling. In the present study, the effects of lanthanum carbonate were
      examined in an animal model that mimics low turnover bone disease in CKD, i.e.,
      thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a
      constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH
      5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis
      revealed that both bone formation and resorption were markedly suppressed in the
      TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment
      with lanthanum carbonate was associated with the stimulation of bone formation
      but not an acceleration of bone resorption. Lanthanum treatment caused a robust
      stimulation of bone formation with an activation of osteoblasts on the endosteal
      surface of femoral diaphysis, leading to an increase in cortical bone volume.
      Thus, lanthanum carbonate has the potential to stimulate bone formation in cases
      of CKD-MBD with suppressed bone turnover. 

PMID- 24126695
TI  - Effect of liver dysfunction on circulating sclerostin.
AB  - Sclerostin is a Wnt inhibitor produced specifically by osteocytes. It decreases
      bone formation by repressing osteoblast differentiation and proliferation.
      Whether circulating sclerostin level is affected by liver function is not
      currently clear. The aim of the study was to evaluate this relationship. Our
      cross-sectional study included 47 patients with liver cirrhosis and 50 healthy
      controls. Serum sclerostin level was analyzed by ELISA. Serum sclerostin levels
      were significantly higher in patients with cirrhosis than in controls (50.8 +/-
      38.2 vs. 35.1 +/- 8.8 pmol/L, p = 0.008). After further adjustment for age, sex,
      body mass index, serum creatinine, and presence of diabetes, cirrhosis patients
      had higher sclerostin than controls. Subgroup analysis found that patients with
      Child-Pugh class B or C had higher sclerostin levels than patients with class A
      or controls after adjusting for multiple confounding factors. Multiple regression
      analysis showed that gender (p = 0.022), presence of diabetes (p < 0.001),
      albumin (p = 0.010), and serum creatinine (p = 0.037) were independent factors
      for circulating sclerostin level. Circulating sclerostin was higher in patients
      with advanced liver cirrhosis than in healthy controls or patients with early
      liver cirrhosis. The elevated sclerostin levels clearly correlated with markers
      of liver dysfunction such as albumin. The relationship between circulating
      sclerostin and liver function indicates a possible role of the liver in
      sclerostin metabolism.

PMID- 24126696
TI  - Color degradation of acrylic resin denture teeth as a function of liquid diet:
      ultraviolet-visible reflection analysis.
AB  - The effect of different beverages on acrylic resin denture teeth color
      degradation is evaluated. Ten acrylic resin denture teeth brands were evaluated:
      Art Plus (AP), Biolux (BX), Biotone IPN (BI), Magister (MG), Mondial 6 (MD),
      Premium 6 (PR), SR Vivodent PE (SR), Trilux (TR), Trubyte Biotone (TB), and Vipi
      Dent Plus (VP). Teeth were immersed in staining solutions (coffee, cola, and
      orange juice) or artificial saliva (control) (n=6) for 1, 7, 15, or 30 days.
      Specimen colors were evaluated spectrophotometrically based on the Commission
      Internationale d'Eclairage L*a*b* system. Color differences (DeltaE) were
      calculated between the baseline and post-staining results. Data were evaluated by
      analysis of variance and Tukey test (alpha = 0.05). BI (1.82 +/- 0.95) and TR
      (1.78 +/- 0.72) teeth exhibited the greatest DeltaE values, while BX (0.88 +/-
      0.43) and MD (1.09 +/- 0.44) teeth were the lowest, regardless of solution and
      measurement period, and were different from BI and TR teeth (P < 0.05). Cola and
      coffee promoted higher denture teeth color alterations than orange juice and
      saliva (P < 0.05). Saliva generated the lowest denture teeth color alterations.
      Greater immersion times caused higher denture teeth color changes. The lifespan
      of removable dentures and the aesthetic satisfaction of several edentulous
      patients may be increased with the use of stain-resistant artificial denture
      teeth.

PMID- 24126697
TI  - Induction of p53 expression and apoptosis by a recombinant dual-target MDM2/MDMX
      inhibitory protein in wild-type p53 breast cancer cells.
AB  - The tumor suppressor gene p53 is often inactivated in breast cancer cells due to
      gene mutation or overexpression of its repressors (such as murine double minute 2
      and murine double minute X). Inhibitors of murine double minute 2 (MDM2) and
      murine double minute X (MDMX) could lead to tumor suppression by restoration of
      p53 activity and such an approach is a promising strategy for future control of
      breast cancer. This study aimed to investigate the feasibility of the recombinant
      MDM2 and MDMX inhibitory protein in control of breast cancer in vitro. A cell
      permeable dual-target MDM2/MDMX inhibitory protein was expressed in E. coli and
      incubated with p53 wild-type breast cancer cells. The data showed that this
      recombinant MDM2/MDMX inhibitory protein reduced the viability of MCF-7 and ZR-75
      30 breast cancer cell lines and promoted cell cycle arrest and apoptosis by
      activation and stabilization of the p53 protein. Mechanistically, this MDM2/MDMX
      inhibitory protein increased the expression of p21, Bax and puma proteins, and
      inhibitory expression of MDM2 and MDMX proteins. This recombinant protein showed
      a better in vitro effect than that of nutlin-3alpha, a small molecule MDM2
      inhibitor. The data further support the hypothesis that targeting of the p53 gene
      pathway could effectively control breast cancer.

PMID- 24126698
TI  - Adsorptive removal of Cr(vi) from wastewater by alpha-FeOOH hierarchical
      structure: kinetics, equilibrium and thermodynamics.
AB  - A novel hollow urchin-like alpha-FeOOH hierarchical structure was fabricated via
      a one-pot hydrothermal procedure without using any templates, surfactants or
      organic raw materials. An inside-out amorphous ripening mechanism was proposed to
      unravel its structural evolution. The kinetics, equilibrium and thermodynamics of
      its adsorptive removal of Cr(vi) from wastewater were comprehensively
      investigated. It was found that the adsorption process can be depicted using a
      pseudo-second-order model, and a high adsorption capacity of 58.97 mg g(-1) was
      obtained from the equilibrium adsorption isotherm. Also, the thermodynamic
      parameters (i.e., enthalpy, entropy and Gibbs free energy) at different
      temperatures were acquired to reveal a spontaneous adsorption process, with both
      physical and chemical characteristics. 

PMID- 24126699
TI  - Bone: Hedgehog signalling linked to heterotopic ossification in POH.

PMID- 24126700
TI  - Connective tissue diseases: Integrins crucial for the onset of fibrosis in
      systemic sclerosis--a new therapeutic target?

PMID- 24126702
TI  - Well-organized raspberry-like Ag@Cu bimetal nanoparticles for highly reliable and
      reproducible surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman scattering (SERS) is ideally suited for probing and
      mapping surface species and incipient phases on fuel cell electrodes because of
      its high sensitivity and surface-selectivity, potentially offering insights into
      the mechanisms of chemical and energy transformation processes. In particular,
      bimetal nanostructures of coinage metals (Au, Ag, and Cu) have attracted much
      attention as SERS-active agents due to their distinctive electromagnetic field
      enhancements originated from surface plasmon resonance. Here we report excellent
      SERS-active, raspberry-like nanostructures composed of a silver (Ag) nanoparticle
      core decorated with smaller copper (Cu) nanoparticles, which displayed enhanced
      and broadened UV-Vis absorption spectra. These unique Ag@Cu raspberry
      nanostructures enable us to use blue, green, and red light as the excitation
      laser source for surface-enhanced Raman spectroscopy (SERS) with a large
      enhancement factor (EF). A highly reliable SERS effect was demonstrated using
      Rhodamine 6G (R6G) molecules and a thin film of gadolinium doped ceria. 

PMID- 24126701
TI  - Psychological predictors of anterior cruciate ligament reconstruction outcomes: a
      systematic review.
AB  - PURPOSE: Lack of return to sport following anterior cruciate ligament (ACL)
      reconstruction often occurs despite adequate restoration of knee function, and
      there is growing evidence that psychological difference among patients may play
      an important role in this discrepancy. The purpose of this review is to identify
      baseline psychological factors that are predictive of clinically relevant ACL
      reconstruction outcomes, including return to sport, rehab compliance, knee pain,
      and knee function. METHODS: A systematic search was performed in PubMed, Google
      Scholar, CINAHL, UptoDate, Cochrane Reviews, and SportDiscus, which identified
      1,633 studies for potential inclusion. Inclusion criteria included (1)
      prospective design, (2) participants underwent ACL reconstruction, (3)
      psychological traits assessed at baseline, and (4) outcome measures such as
      return to sport, rehabilitation compliance, and knee symptoms assessed.
      Methodological quality was evaluated with a modified Coleman score with several
      item-specific revisions to improve relevance to injury risk assessment studies in
      sports medicine. RESULTS: Eight prospective studies were included (modified
      Coleman score 63 +/- 4.9/90, range 55-72). Average study size was 83 +/- 42
      patients with median 9-month follow-up (range 3-60 months). Measures of self
      efficacy, self-motivation, and optimism were predictive of rehabilitation
      compliance, return to sport, and self-rated knee symptoms. Pre-operative stress
      was negatively predictive, and measures of social support were positively
      predictive of knee symptoms and rehabilitation compliance. Kinesiophobia and pain
      catastrophizing at the first rehabilitation appointment did not predict knee
      symptoms throughout the early rehabilitation phase (n.s.). CONCLUSIONS: Patient
      psychological factors are predictive of ACL reconstruction outcomes. Self
      confidence, optimism, and self-motivation are predictive of outcomes, which is
      consistent with the theory of self-efficacy. Stress, social support, and athletic
      self-identity are predictive of outcomes, which is consistent with the global
      relationship between stress, health, and the buffering hypothesis of social
      support.

PMID- 24126703
TI  - Children with asthma and their families' viewpoints on spiritual and
      psychological resources in adaptation with the disease.
AB  - Recognition of the spiritual and psychological needs of children and their
      families with chronic asthma disease may be helpful in a successful coping with
      their problems in order to control over the condition. In a qualitative content
      analysis study, nine children with moderate to severe asthma and 10 parents were
      studied in order to discover the resources of compatibility of them. The
      participants were chosen purposefully and they were asked some semi-structure
      questions about their experiences. The spiritual and psychological experiences of
      the participants were divided into two main categories as follows: (1) contrive
      to religious-belief consisting of three sub-categories known as "religious
      rituals, believe in a divine predestination, and Islamic-based patience," and (2)
      psycho-intellectual management that includes the five sub-categories of "psycho
      intellectual attention, maintaining family's mental peace, reduction in negative
      burden of disease, satisfaction from optimal treatment, and matching internal
      desires with disease conditions." It is recommended that heath care providers by
      reinforcing parent's and children's religious and spiritual backgrounds and
      according to child's cognitive development at this age provide a suitable
      foreground through necessary instructions for children and their families in
      order to spiritual growth and suitable adaptation with disease. 

PMID- 24126704
TI  - miR-21 is a critical therapeutic target for renal fibrosis.

PMID- 24126705
TI  - An education program for risk factor management after an acute coronary syndrome:
      a randomized clinical trial.
AB  - IMPORTANCE: Lifestyle improvements after an acute coronary syndrome reduce
      cardiovascular risk but are difficult to achieve. OBJECTIVE: To determine whether
      a nurse-led or dietician-led cardiovascular risk factor education program would
      improve risk factor reduction over the long term after an acute coronary
      syndrome. DESIGN, SETTING, AND PARTICIPANTS: The Reseau Insuffisance Cardiaque
      (RESICARD) PREVENTION: study was a 2-arm, parallel-group, multicenter, randomized
      clinical trial at 6 tertiary care hospitals in France. Patients hospitalized in a
      cardiac intensive care unit for an acute coronary syndrome with at least 1
      lifestyle risk factor (current smoking, sedentary lifestyle, or overweight or
      obesity) were randomized according to a computer-generated list with sequentially
      numbered, sealed envelopes. INTERVENTION: Patients underwent an education program
      in a unique non-hospital setting (a House of Education) or were treated according
      to physicians' usual standard of care. MAIN OUTCOMES AND MEASURES: The primary
      outcome was a composite that included at least 1 of the following: smoking
      cessation, at least 3 hours per week of physical activity, at least 5% reduction
      in weight, and at least 4% reduction in waist circumference. Patients were
      followed up for 1 year. An intent-to-treat analysis was performed. RESULTS From
      June 21, 2006, to July 30, 2008, a total of 251 patients were randomized to the
      House of Education and 251 to conventional care. The 2 groups did not differ
      significantly at 12 months in the primary composite outcome (51.8% vs 49.8%
      success rate; adjusted relative risk [aRR], 1.11; 95% CI, 0.90-1.37) or with
      correction of all risk factors (aRR, 1.22; 95% CI, 0.89-1.66). Similarly, the 2
      groups did not differ by physical activity (aRR, 1.05; 95% CI, 0.92-1.21),
      smoking cessation (aRR, 0.99; 95% CI, 0.87-1.13), and weight or waist reduction
      (aRR, 1.07; 95% CI, 0.84-1.36). CONCLUSIONS AND RELEVANCE: Compared with
      conventional care, the House of Education did not result in superior improvement
      in lifestyle-related cardiovascular risk factors after an acute coronary
      syndrome. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00337480.

PMID- 24126706
TI  - Transferring protection: adenosine as the Lone Ranger? : editorial to: "Remote
      cardioprotection by transfer of coronary effluent from ischemic preconditioned
      rabbit heart preserves mitochondrial integrity and function via adenosine
      receptor activation" by C.H. Leung et al.

PMID- 24126708
TI  - Association of common genetic variants of HOMER1 gene with levodopa adverse
      effects in Parkinson's disease patients.
AB  - Levodopa is the most effective symptomatic therapy for Parkinson's disease, but
      its chronic use could lead to chronic adverse outcomes, such as motor
      fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with
      pivotal function in glutamate transmission, which has been related to the
      pathogenesis of these complications. This study investigates whether
      polymorphisms in the HOMER1 gene promoter region are associated with the
      occurrence of the chronic complications of levodopa therapy. A total of 205
      patients with idiopathic Parkinson's disease were investigated. Patients were
      genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with
      Taqman assays. The rs4704559 G allele was associated with a lower prevalence of
      dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426
      0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899,
      P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role
      for the development of levodopa adverse effects. 

PMID- 24126707
TI  - Genetic variation in OPRD1 and the response to treatment for opioid dependence
      with buprenorphine in European-American females.
AB  - Two commonly prescribed treatments for opioid addiction are methadone and
      buprenorphine. Although these drugs show some efficacy in treating opioid
      dependence, treatment response varies among individuals. It is likely that
      genetic factors have a role in determining treatment outcome. This study analyses
      the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding
      the delta-opioid receptor, on treatment outcome in 582 opioid addicted European
      Americans randomized to either methadone or buprenorphine/naloxone (Suboxone)
      over the course of a 24-week open-label clinical trial. Treatment outcome was
      assessed as the number of missed or opioid-positive urine drug screens over the
      24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1
      were significantly associated with treatment outcome in either treatment arm.
      However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520)
      that predicted treatment outcome in females treated with buprenorphine. Females
      with the AA or AG genotypes at rs581111 had significantly worse outcomes than
      those with the GG genotype when treated with buprenorphine (P=0.03, relative risk
      (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the
      AA genotype had a significantly worse outcome than those with the CC genotype
      when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were
      detected in males. These findings suggest that rs581111 and rs52920 may be useful
      when considering treatment options for female opioid addicts, however,
      confirmation in an independent sample is warranted. 

PMID- 24126709
TI  - Selectivity of Ni(II) and Zn(II) binding to Sporosarcina pasteurii UreE, a
      metallochaperone in the urease assembly: a calorimetric and crystallographic
      study.
AB  - Urease is a nickel-dependent enzyme that plays a critical role in the
      biogeochemical nitrogen cycle by catalyzing the hydrolysis of urea to ammonia and
      carbamate. This enzyme, initially synthesized in the apo form, needs to be
      activated by incorporation of two nickel ions into the active site, a process
      driven by the dimeric metallochaperone UreE. Previous studies reported that this
      protein can bind different metal ions in vitro, beside the cognate Ni(II). This
      study explores the metal selectivity and affinity of UreE from Sporosarcina
      pasteurii (Sp, formerly known as Bacillus pasteurii) for cognate [Ni(II)] and
      noncognate [Zn(II)] metal ions. In particular, the thermodynamic parameters of
      SpUreE Ni(II) and Zn(II) binding have been determined using isothermal titration
      calorimetry. These experiments show that two Ni(II) ions bind to the protein
      dimer with positive cooperativity. The high-affinity site involves the conserved
      solvent-exposed His(100) and the C-terminal His(145), whereas the low-affinity
      site comprises also the C-terminal His(147). Zn(II) binding to the protein,
      occurring in the same protein regions and with similar affinity as compared to
      Ni(II), causes metal-driven dimerization of the protein dimer. The crystal
      structure of the protein obtained in the presence of equimolar amounts of both
      metal ions indicates that the high-affinity metal binding site binds Ni(II)
      preferentially over Zn(II). The ability of the protein to select Ni(II) over
      Zn(II) was confirmed by competition experiments in solution as well as by
      analysis of X-ray anomalous dispersion data. Overall, the thermodynamics and
      structural parameters that modulate the metal ion specificity of the different
      binding sites on the protein surface of SpUreE have been established. 

PMID- 24126710
TI  - Mechanisms of antiplatelet activity of nifedipine: role of peroxisome
      proliferator-activated receptor-beta-gamma-dependent processes.
AB  - OBJECTIVE: Nifedipine, an L-type calcium channel blocker, is widely used in the
      treatment of hypertension and coronary heart diseases, and also exhibits an
      antiplatelet activity. Activation of peroxisome proliferator-activated receptors
      (PPARs; alpha, beta/delta, and gamma) inhibits the platelet aggregation.
      Therefore, the purpose of this study was to evaluate the contribution of PPAR
      mediated processes to the antiplatelet activity of nifedipine. METHODS AND
      RESULTS: We assessed human platelet aggregation by using an aggregometer and
      measured several platelet activating markers and related signaling pathways in
      platelets treated with nifedipine in the presence or absence of PPAR agonists.
      Nifedipine treatment (1, 5  MUmol/l) dose-dependently increased the activity and
      intracellular expression of PPAR-beta/-gamma by inhibiting the release of PPAR
      beta/-gamma from activated platelets. Nifedipine treatment also upregulated
      cyclic 3',5'-cyclic monophosphate (GMP)/protein kinase G (PKG) expression, and
      increased PI(3)K/Akt pathway, endothelial nitric oxide synthase, and soluble
      guanylyl cyclase activities. In the presence of a selective PPAR-beta antagonist
      (GSK0660) or PPAR-gamma antagonist (GW9662), the inhibitory effects of nifedipine
      on collagen-induced platelet aggregation, intracellular Ca mobilization, and
      protein kinase C (PKC-alpha) activation were abrogated. Similarly, PPAR-beta
      gamma antagonists markedly attenuated nifedipine-mediated upregulation of nitric
      oxide/cyclic GMP/PKG cascade. In a mouse model of thrombosis, the administration
      of nifedipine substantially inhibited fluorescein sodium-induced vessel thrombus
      formation; however, the antithrombotic effect was considerably reduced in the
      presence of PPAR-beta/-gamma antagonists. CONCLUSION: This study is the first to
      show that the PPAR-beta/-gamma-dependent upregulation of PI(3)K/Akt/nitric
      oxide/cyclic GMP/PKG pathway and the inhibition of PKC-alpha activity and
      intracellular Ca(+) mobilization in platelets may be the mechanisms underlying
      the antiplatelet and antithrombotic activities of nifedipine.

PMID- 24126711
TI  - Undiagnosed hypertension among young adults with regular primary care use.
AB  - OBJECTIVE: Young adults meeting hypertension diagnostic criteria have a lower
      prevalence of a hypertension diagnosis than middle-aged and older adults. The
      purpose of this study was to compare the rates of a new hypertension diagnosis
      for different age groups and identify predictors of delays in the initial
      diagnosis among young adults who regularly use primary care. METHODS: A 4-year
      retrospective analysis included 14 970 patients, at least 18 years old, who met
      clinical criteria for an initial hypertension diagnosis in a large, Midwestern,
      academic practice from 2008 to 2011. Patients with a previous hypertension
      diagnosis or prior antihypertensive medication prescription were excluded. The
      probability of diagnosis at specific time points was estimated by Kaplan-Meier
      analysis. Cox proportional hazard models (hazard ratio; 95% confidence interval)
      were fit to identify predictors of delays to an initial diagnosis, with a
      subsequent subset analysis for young adults (18-39 years old). RESULTS: After 4
      years, 56% of 18-24-year-olds received a diagnosis compared with 62% (25-31-year
      olds), 68% (32-39-year-olds), and more than 70% (>=40-year-olds). After
      adjustment, 18-31-year-olds had a 33% slower rate of receiving a diagnosis (18-24
      years hazard ratio 0.66, 0.53-0.83; 25-31 years hazard ratio 0.68, 0.58-0.79)
      compared with adults at least 60 years. Other predictors of a slower diagnosis
      rate among young adults were current tobacco use, white ethnicity, and non
      English primary language. Young adults with diabetes, higher blood pressures, or
      a female provider had a faster diagnosis rate. CONCLUSION: Provider and patient
      factors are critical determinants of poor hypertension diagnosis rates among
      young adults with regular primary care use.

PMID- 24126712
TI  - Determinants of left ventricular hypertrophy in patients with recent diagnosis of
      essential hypertension.
AB  - OBJECTIVE: Development of left ventricular hypertrophy (LVH) is a multifactorial
      phenomenon. We retrospectively assessed the risk factors for LVH in patients with
      recent diagnosis of essential hypertension. METHODS: We analysed 1518
      participants with recent diagnosis of essential hypertension (<=2 years). The
      duration of hypertension was established after cross-checking the patients'
      history and the records of the general practitioners'. The following
      cardiovascular (CV) risk factors were considered: age (men >55 years, women >65
      years), SBP >140  mmHg, DBP >90  mmHg, obesity, diabetes, hypercholesterolemia,
      low or high-density lipoprotein (HDL)-cholesterol (men <40  m/dl, women <50 
      mg/dl), and chronic kidney disease (CKD). RESULTS: Age, prevalence of metabolic
      diseases, CKD, and the severity of hypertension were higher in patients with LVH.
      One hundred twenty-two (8%) patients did not have CV risk factors, whereas 288
      (19%), 472 (31.1%), 351 (23.1%) and 285 (18.8%) patients had one, two, three and
      more than three CV risk factors, respectively. At univariate analysis, CV risk
      factors for LVH where found to be sex, age, SBP, low HDL-cholesterol, obesity,
      diabetes, CKD, and metabolic syndrome. In the multivariate analysis, the
      independent predictors of LVH were found to be sex, age, SBP, obesity and
      diabetes. A significant correlation was found between indexed left ventricular
      mass and body mass index (r(2) = 0.167), age (r(2) = 0.077) and SBP (r (2)=
      0.055). CONCLUSION: This study reveals that, in patients with recent diagnosis of
      essential hypertension obesity represents the most important modifiable CV risk
      factor for LVH.

PMID- 24126713
TI  - Lack of difference between nebivolol/hydrochlorothiazide and
      metoprolol/hydrochlorothiazide on aortic wave augmentation and central blood
      pressure.
AB  - BACKGROUND: The vasodilating beta-blocker nebivolol is thought to be superior in
      lowering wave reflection and central blood pressure (BP) compared to
      nonvasodilating beta-blockers. The results from studies comparing nebivolol with
      either metoprolol or atenolol, with or without hydrochlorothiazide (HCTZ), are
      not unequivocal. METHODS: We examined the effects of nebivolol 5 mg and
      metoprolol 100 mg with HCTZ 12.5 mg on aortic wave augmentation, central BP and
      hemodynamics using a randomized, double-blind, crossover design. We included 22
      patients (17 men, age 59.9 +/- 6.4 years) with office SBP of 155 +/- 16 mmHg and
      DBP of 93 +/- 10 mmHg. Radial applanation tonometry and noninvasive, continuous
      finger arterial BP measurement was performed at baseline and after 4 weeks of
      treatment with either drug regimen, separated by a 4-week washout period.
      RESULTS: Neither treatment affected aortic wave augmentation significantly.
      Augmentation index increased 1.0 +/- 7.8% (P = 0.5) for nebivolol/HCTZ and 2.4 +/
      6.6% (P = 0.07) for metoprolol/HCTZ. Nebivolol/HCTZ lowered central SBP by 15.8
      +/- 14.9 mmHg and DBP 10.5 +/- 8.4 mmHg, and with metoprolol/HCTZ by 13.5 +/-
      12.3 mmHg for SBP and 9.5 +/- 6.8 mmHg for DBP (all P < 0.001). Heart rate was
      lowered 8.1 +/- 5.4 beats/min by nebivolol/HCTZ and 8.6 +/- 4.9 beats/min by
      metoprolol/HCTZ. Peripheral BP was reduced to a similar extent as central BP.
      Peripheral BP decreased by 16.3 +/- 14.9 mmHg systolic and 10.1 +/- 8.2 mmHg
      diastolic with nebivolol/HCTZ, and by 15.2 +/- 13.0 mmHg systolic and 9.1 +/- 6.9
      mmHg diastolic with metoprolol/HCTZ. Both treatment modalities had a similar
      effect on stroke volume, cardiac output, left-ventricular contractility and
      peripheral resistance. CONCLUSION: Nebivolol was not superior to metoprolol in
      reducing aortic wave augmentation or central BP when combined with HCTZ.

PMID- 24126714
TI  - Stereotyped distribution of midbody remnants in early C. elegans embryos requires
      cell death genes and is dispensable for development.

PMID- 24126715
TI  - Structure reveals that BAK1 as a co-receptor recognizes the BRI1-bound
      brassinolide.

PMID- 24126716
TI  - Aerosolized antibiotics: do they add to the treatment of pneumonia?
AB  - PURPOSE OF REVIEW: The increasing rate of ventilator-associated pneumonia (VAP)
      caused by multidrug-resistant pathogens warrants the development of new treatment
      strategies. Carefully engineered delivery systems are undergoing evaluation to
      test the hypothesis that aerosolized administration of antibiotics will provide
      high local concentrations and fast clearance, which in turn may improve efficacy
      and decrease the risk of microbial resistance. RECENT FINDINGS: Recent studies
      indicate that aerosolized delivery systems for specially formulated antibiotics
      yield high local concentrations with rapid clearance and low systemic exposure.
      Preliminary clinical studies reveal that aerosolized delivery of antibiotics is
      well tolerated and active, when combined with intravenous antibiotics. No single
      aerosolized antibiotic is likely to provide broad-spectrum activity against both
      Gram-negative and Gram-positive bacteria. SUMMARY: Large multicenter trials are
      needed to determine whether preliminary findings will translate to improved
      clinical activity and decreased microbial resistance in VAP patients, and to
      optimize the use of aerosolized antibiotics.

PMID- 24126717
TI  - Antimicrobial stewardship's new weapon? A review of antibiotic allergy and
      pathways to 'de-labeling'.
AB  - PURPOSE OF REVIEW: The continued emergence of multiresistant pathogens and
      widespread antimicrobial use has led to a greater emphasis on antimicrobial
      stewardship programs. Concurrently, an increased awareness of the rising number
      of antibiotic allergy labels and impact on antimicrobial use has surfaced. The
      integration of antibiotic allergy de-labeling and antimicrobial stewardship
      programs may be a pathway worthy of further focus and investigation. RECENT
      FINDINGS: Recent literature has evaluated the efficacy of antibiotic allergy
      management (historical de-labeling, in-vitro testing, skin prick testing,
      intradermal testing, and oral challenges) and impact of antibiotic allergy labels
      on patient outcome. The importance of true and perceived antibiotic allergy cross
      reactivity in the setting of beta-lactam allergies has been highlighted. The
      impact of dedicated antibiotic allergy de-labeling clinics, inpatient antibiotic
      allergy testing, and integrated antimicrobial stewardship programs has been
      recently appraised. SUMMARY: More recent literature supports that appropriate
      antibiotic allergy in-vitro and in-vivo testing and subsequent antibiotic allergy
      de-labeling, particularly in regard to beta-lactams, can decrease broad-spectrum
      antibiotic use, costs, patient length of stay, and mortality. Integration of
      antibiotic allergy management into the decision support systems of inpatient and
      outpatient antimicrobial stewardship programs represents an important opportunity
      to further improve measured outcomes from antibiotic utilization.

PMID- 24126719
TI  - Azole resistance in Aspergillus fumigatus: a growing public health concern.
AB  - PURPOSE OF REVIEW: Reports from the end of the 2000s forced the medical community
      to take azole resistance in Aspergillus fumigatus into account. Not only patients
      with chronic aspergillus disease, who develop resistance during long-term azole
      treatment, but also azole-naive patients are at risk, owing to the presence of
      resistant strains in the environment. The purpose of this review is to overview
      the latest findings concerning the origin, evolution, and implications of azole
      resistance in A. fumigatus. RECENT FINDINGS: TR34/L98H is the predominant
      resistance mechanism of environmental origin in A. fumigatus. Recent
      epidemiological data show that this mechanism is an expanding problem, with
      reports from China, Iran, and India. However, the TR34/L98H strains from the
      Middle East are genotypically different from the European isolates; their
      emergence is, therefore, not due to simple geographical spread of the 'European'
      isolates. A new environmental resistance mechanism, TR46/Y121F/T289A, was
      detected in the Netherlands, conferring voriconazole resistance. In patients
      chronically treated with triazoles, the spectrum of resistance has become more
      diverse, with the emergence of non-CYP51A-mediated mechanisms. Central
      registration of treatment and outcome data of patients with resistant aspergillus
      disease are needed. SUMMARY: Azole resistance in A. fumigatus is evolving to a
      global health problem.

PMID- 24126718
TI  - Update on mucormycosis pathogenesis.
AB  - PURPOSE OF REVIEW: Mucormycosis is an increasingly common fungal infection with
      unacceptably high mortality. The recent sequencing genome projects of Mucorales
      and the development of gene manipulation have enabled significant advances in
      understanding the pathogenesis of mucormycosis. Therefore, we review the
      pathogenesis of mucormycosis and highlight potential development of novel
      diagnostic and therapeutic modalities against this lethal disease. RECENT
      FINDINGS: Much of the work has been focused on the role of iron uptake in the
      virulence of Mucorales. Additionally, host receptors and fungal ligands involved
      in the process of tissue invasion as well as sporangiospore size and sex loci and
      their contribution to virulence of Mucorales are discussed. Finally, the role of
      innate and adaptive immunity in protection against Mucorales and new evidence
      about drug-induced apoptosis in these fungi are discussed. SUMMARY: Recent
      discoveries introduce several potentially novel diagnostic and therapeutic
      modalities, which are likely to improve management and outcome for mucormycosis.
      Future preclinical and clinical research is warranted to develop these diagnostic
      and therapeutic strategies.

PMID- 24126720
TI  - Fungal endocarditis.
AB  - PURPOSE OF REVIEW: Fungal endocarditis remains a rare disease occurring mostly in
      patients with predisposing host conditions. Regarding its poor prognosis because
      of severe complications, there is an urgent need for properly established
      treatment guidelines and prophylaxis for patients at risk. In this review we
      provide up-to-date information on treatment recommendations, and discuss recent
      case reports on fungal endocarditis and challenges in prophylaxis and treatment.
      RECENT FINDINGS: Over the last year, an increase in cases caused by non-albicans
      species of Candida and other fungi like Fusarium solani, Lodderomyces
      elongisporus and Exophiala dermatitidis was reported. They were treated
      individually in case-by-case approaches, lacking randomized controlled trials
      and, mostly, treatment recommendations. SUMMARY: The scarcity of fungal
      endocarditis demands a high index of suspicion and knowledge of the group of at
      risk patients. Diagnosis aggressively pursued by echocardiography and multiple
      blood cultures or surgical specimens has the potential to improve outcome.
      Candida endocarditis should be treated immediately, including surgical treatment
      in combination with liposomal amphotericin B or caspofungin with optional
      addition of flucytosine. Aspergillus endocarditis requires rapid surgery and
      voriconazole.

PMID- 24126721
TI  - New opportunities for control of dengue virus.
AB  - PURPOSE OF REVIEW: Dengue is a rapidly spreading vector-borne disease estimated
      to infect 400 million people worldwide. To date, there are no licensed treatments
      or vaccines. The last few years have seen significant developments in dengue
      control strategies. In this review, we will address four key areas: vaccines,
      vector control, antivirals and immunotherapeutics. RECENT FINDINGS: The first
      generation of dengue vaccines is able to induce good serological responses in
      test individuals. However, the recent Sanofi-Pasteur trial in Thailand found that
      a good serological response did not correlate with clinical protection. This
      trial did not demonstrate an increase in cases of severe disease following
      immunization, suggesting that concerns over vaccine-related immune enhancement
      may have been overcome. The bacterium Wolbachia appears to control dengue
      proliferation in Aedes mosquitoes, and field studies are underway. A large number
      of antivirals are in early-stage development and may prove useful in epidemics.
      Monoclonal antibodies have been postulated to have a clinical role. Whether their
      clinical application is feasible has yet to be seen. SUMMARY: Marked improvements
      in our knowledge of dengue have been made over the recent years. Sadly, clinical
      application remains some years away.

PMID- 24126722
TI  - Photosynthetic assimilation of 14C into amino acids in potato (Solanum tuberosum)
      and asparagine in the tubers.
AB  - Asparagine is the predominant free amino acid in potato tubers and the present
      study aimed to establish whether it is imported from the leaves or synthesised in
      situ. Free amino acid concentrations are important quality determinants for
      potato tubers because they react with reducing sugars at high temperatures in the
      Maillard reaction. This reaction produces melanoidin pigments and a host of aroma
      and flavour volatiles, but if free asparagine participates in the final stages,
      it results in the production of acrylamide, an undesirable contaminant. 14CO2 was
      supplied to a leaf or leaves of potato plants (cv. Saturna) in the light and
      radioactivity incorporated into amino acids was determined in the leaves, stems,
      stolons and tubers. Radioactivity was found in free amino acids, including
      asparagine, in all tissues, but the amount incorporated in asparagine transported
      to the tubers and stolons was much less than that in glutamate, glutamine, serine
      and alanine. The study showed that free asparagine does not play an important
      role in the transport of nitrogen from leaf to tuber in potato, and that the high
      concentrations of free asparagine that accumulate in potato tubers arise from
      synthesis in situ. This indicates that genetic interventions to reduce free
      asparagine concentration in potato tubers will have to target asparagine
      metabolism in the tuber.

PMID- 24126723
TI  - Global gene expression in rice blast pathogen Magnaporthe oryzae treated with a
      natural rice soil isolate.
AB  - The rhizospheric microbiome is comprised of many microbes, some of which reduce
      the virulence of their phytopathogenic neighbors; however, the mechanisms
      underlying these interactions are largely unknown. Rice soil isolate Pseudomonas
      chlororaphis EA105 strongly inhibits Magnaporthe oryzae's in vitro growth by
      restricting fungal diameter as well as inhibiting the formation of the
      appressorium, required for penetration. We were interested in elucidating M.
      oryzae's response to EA105 treatment, and utilized a microarray approach to
      obtain a global perspective of EA105 elicited changes in this pathogen. Based on
      this analysis, three genes of interest were knocked out in M. oryzae 70-15, and
      their sensitivity to EA105 treatment as well as their ability to infect rice was
      determined. Priming rice plants with EA105 prior to M. oryzae infection decreased
      lesion size, and the mutants were tested to see if this effect was retained. A
      null 70-15 mutant in a trichothecene biosynthesis gene showed less susceptibility
      to bacterial treatment, forming more appressoria than the parental type 70-15. A
      similar pattern was seen in a null mutant for a stress-inducible protein,
      MGG_03098. In addition, when this mutant was inoculated onto the leaves of EA105
      primed rice plants, lesions were reduced to a greater extent than in 70-15,
      implicating the lack of this gene with an increased ISR response in rice.
      Understanding the global effect of biocontrol bacteria on phytopathogens is a key
      for developing successful and lasting solutions to crop loss caused by plant
      diseases and has the potential to greatly increase food supply. 

PMID- 24126724
TI  - Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney
      disease.
AB  - Rosiglitazone (ROG) has been shown to exert beneficial effects on glycemic
      control and renal protection. Circulatory fibroblast growth factor-23 (FGF-23) is
      a novel independent risk factor for chronic kidney disease (CKD) progression. The
      current study focused on how ROG impacts on injury of the kidney, and whether FGF
      23 is involved in the process. A total of 24 male Sprague Dawley rats, weighing
      250-280 g, were divided into four groups (n=6 per group): i) Normal; ii) ROG
      controls, treated with ROG (10 mg/kg/day); iii) CKD models, treated with adenine
      (200 mg/kg/day); and iv) ROG treatment, treated with ROG (10 mg/kg/day) and
      adenine (200 mg/kg/day). The rats were sacrificed after four weeks, and serum,
      urine and kidney tissues were collected. The data revealed that the serum levels
      of inorganic phosphate (Pi), intact parathyroid hormone (iPTH) and FGF-23 were
      significantly higher in the CKD models compared with those in the normal group
      (P<0.01), while ROG significantly reduced the serum levels of Pi, iPTH and FGF-23
      (P<0.01). The ratio of protein/creatine (Cr) in the urine and the serum levels of
      Cr, blood urea nitrogen and uric acid were significantly increased in the CKD
      models compared with the normal group (P<0.01), however, ROG significantly
      reduced these parameters (P<0.05). Furthermore, ROG significantly alleviated the
      tubule interstitial damage index of the CKD models in comparison with that of the
      controls. These results indicated that ROG mitigates the lesions of chronic
      kidney disease induced by adenine, and that the system of Pi-PTH-FGF-23 may
      contribute to this process. The possible mechanisms underlying this process
      require confirmation in future studies.

PMID- 24126725
TI  - Method for rapid multidiameter single-fiber reflectance and fluorescence
      spectroscopy through a fiber bundle.
AB  - We have recently demonstrated a means for quantifying the absorption and
      scattering properties of biological tissue through multidiameter single-fiber
      reflectance (MDSFR) spectroscopy. These measurements can be used to correct
      single-fiber fluorescence (SFF) spectra for the influence of optical properties,
      enabling quantification of intrinsic fluorescence. In our previous work, we have
      used a series of pinholes to show that selective illumination and light
      collection using a coherent fiber bundle can simulate a single solid-core optical
      fiber with variable diameter for the purposes of MDSFR spectroscopy. Here, we
      describe the construction and validation of a clinical MDSFR/SFF spectroscopy
      system that avoids the limitations encountered with pinholes and free-space
      optics. During one measurement, the new system acquires reflectance spectra at
      the effective diameters of 200, 600, and 1000 MUm, and a fluorescence spectrum at
      an effective diameter of 1000 MUm. From these spectra, we measure the absolute
      absorption coefficient, MU(a), reduced scattering coefficient, MU'(s'), phase
      function parameter, gamma, and intrinsic fluorescence, QMU(a,x)(f), across the
      measured spectrum. We validate the system using Intralipid- and polystyrene
      sphere-based scattering phantoms, with and without the addition of the absorber
      Evans Blue. Finally, we demonstrate the combined MDSFR/SFF of phantoms with
      varying concentrations of Intralipid and fluorescein, wherein the scattering
      properties are measured by MDSFR and used to correct the SFF spectrum for
      accurate quantification of QMU(a,x)(f).

PMID- 24126726
TI  - Platelet-derived growth factor C and calpain-3 are modulators of human melanoma
      cell invasiveness.
AB  - The molecular mechanisms responsible for the elevated metastatic potential of
      malignant melanoma are still not fully understood. In order to shed light on the
      molecules involved in the acquisition by melanoma of a highly aggressive
      phenotype, we compared the gene expression profiles of two cell clones derived
      from the human cutaneous metastatic melanoma cell line M14: a highly invasive
      clone (M14C2/MK18) and a clone (M14C2/C4) with low ability to invade the
      extracellular matrix (ECM). The highly invasive phenotype of M14C2/MK18 cells was
      correlated with overexpression of neuropilin-1, activation of a vascular
      endothelial growth factor (VEGF)-A/VEGFR-2 autocrine loop and secretion of matrix
      metalloprotease-2. Moreover, in an in vivo murine model, M14C2/MK18 cells
      displayed a higher growth rate as compared with M14C2/C4 cells, even though in
      vitro both clones possessed comparable proliferative potential. Microarray
      analysis in M14C2/MK18 cells showed a strong upregulation of platelet-derived
      growth factor (PDGF)-C, a cytokine that contributes to angiogenesis, and
      downregulation of calpain-3, a calcium-dependent thiol-protease that regulates
      specific signalling cascade components. Inhibition of PDGF-C with a specific
      antibody resulted in a significant decrease in ECM invasion by M14C2/MK18 cells,
      confirming the involvement of PDGF-C in melanoma cell invasiveness. Moreover, the
      PDGF-C transcript was found to be upregulated in a high percentage of human
      melanoma cell lines (17/20), whereas only low PDGF-C levels were detected in a
      few melanocytic cultures (2/6). By contrast, inhibition of calpain-3 activity in
      M14C2/C4 control cells, using a specific chemical inhibitor, markedly increased
      ECM invasion, strongly suggesting that downregulation of calpain-3 plays a role
      in the acquisition of a highly invasive phenotype. The results indicate that PDGF
      C upregulation and calpain-3 downregulation are involved in the aggressiveness of
      malignant melanoma and suggest that modulators of these proteins or their
      downstream effectors may synergise with VEGF-A therapies in combating tumour
      associated angiogenesis and melanoma spread.

PMID- 24126727
TI  - Is anatomical failure following anterior vaginal repair associated with weak
      native vaginal tissues? A biomechanical and immunohistochemical study.
AB  - INTRODUCTION AND HYPOTHESIS: This study was performed to determine whether
      anatomical recurrence of cystocoele 1 year after anterior vaginal repair is
      related to biomechanical properties and/or the content of collagen in the vaginal
      wall and epithelial tissues. METHODS: In this prospective, observational study in
      a UK teaching hospital, we assessed women undergoing surgery for symptomatic
      anterior compartment prolapse. Outcome measures were anatomical recurrence,
      biomechanical strength and collagen content in vaginal tissues. In part one of
      the study, 42 women underwent biomechanical testing of full-thickness anterior
      vaginal wall tissue samples to determine the elastic moduli and yield stress. In
      part two, 59 women underwent immunohistochemical testing of anterior vaginal wall
      tissue samples to determine tissue content of procollagen I; collagen types I,
      III, V; and matrix metalloproteinases 1 and 2 (MMP-1 and 2). Results were then
      compared with anatomical outcome at 1 year postsurgery. RESULTS: Differences in
      yield strain in all outcome groups (optimal, satisfactory and unsatisfactory)
      were not statistically significant. Considerable variation was found in collagen
      type I in both satisfactory and unsatisfactory groups. There was no difference or
      correlation with procollagen, collagen types III and V, and MMP-1 and recurrence
      of pelvic organ prolapse (POP) between groups. There was a weak correlation
      between collagen type I and higher yield stress in both groups. CONCLUSIONS:
      Anatomical failure of anterior repair does not appear to be related to the
      biomechanical strength or collagen content of the anterior vaginal wall.

PMID- 24126729
TI  - Paediatric urology: cuff-only AUS for refractory neurogenic incontinence.

PMID- 24126730
TI  - Prostate cancer: radium-223: a new treatment option for bone-metastatic CRPC.

PMID- 24126731
TI  - Vesicoureteral reflux--the role of bladder and bowel dysfunction.
AB  - Vesicoureteral reflux (VUR) is a significant risk factor for clinical
      pyelonephritis and renal scarring. In 2010, the American Urological Association
      (AUA) reported that bladder and bowel dysfunction (BBD), which is common in
      patients with VUR, increases the risk of breakthrough UTI in children receiving
      antibiotic prophylaxis, reduces the success rate for endoscopic injection
      therapy, and increases the risk of postoperative UTI, irrespective of the
      surgical success rate for VUR. Accordingly, physicians are strongly recommended
      to investigate BBD in their patients with VUR. Symptoms and signs of BBD include
      urinary frequency and urgency, prolonged voiding intervals, daytime wetting,
      perineal and penile pain, holding manoeuvres (posturing to prevent wetting),
      constipation, and encopresis. Primary assessment tools include the Pediatric
      Symptom Checklist, urinalysis, urine culture, bladder diary, measurement of the
      postvoid residual urine volume, Dysfunctional Voiding Symptom Score, uroflow with
      electromyography, and Bristol Stool Form Score. The Rome III criteria can also be
      used for diagnostic assessment of bowel function. Treatment of BBD should be
      individualized, directed at symptomatic and objective improvement, and can
      include behavioural modification, biofeedback, selective use of anticholinergics
      and alpha-blockers, and bowel management. 

PMID- 24126736
TI  - Outstanding mechanical properties of monolayer MoS2 and its application in
      elastic energy storage.
AB  - The structural and mechanical properties of graphene-like honeycomb monolayer
      structures of MoS2 (g-MoS2) under various large strains are investigated using
      density functional theory (DFT). g-MoS2 is mechanically stable and can sustain
      extra large strains: the ultimate strains are 0.24, 0.37, and 0.26 for armchair,
      zigzag, and biaxial deformation, respectively. The in-plane stiffness is as high
      as 120 N m(-1) (184 GPa equivalently). The third, fourth, and fifth order elastic
      constants are indispensable for accurate modeling of the mechanical properties
      under strains larger than 0.04, 0.07, and 0.13 respectively. The second order
      elastic constants, including in-plane stiffness, are predicted to monotonically
      increase with pressure while the Poisson ratio monotonically decreases with
      increasing pressure. With the prominent mechanical properties including large
      ultimate strains and in-plane stiffness, g-MoS2 is a promising candidate of
      elastic energy storage for clean energy. It possesses a theoretical energy
      storage capacity as high as 8.8 MJ L(-1) and 1.7 MJ kg(-1), or 476 W h kg(-1),
      larger than a Li-ion battery and is environmentally friendly. 

PMID- 24126735
TI  - Infection: targeted IL-12 resets the immune response to gonorrhoea.

PMID- 24126737
TI  - Nano-aggregates of cobalt nickel oxysulfide as a high-performance electrode
      material for supercapacitors.
AB  - Nano-aggregates of cobalt nickel oxysulfide (CoNi)OxSy have been synthesized by
      hydrothermal processing and exhibited specific and areal capacitance as high as
      592 F g(-1) and 1628 mF cm(-2), respectively, at a current density of 0.5 A g(
      1)/1.375 mA cm(-2). They also show high capacitance retention upon extended
      cycling at high rates. 

PMID- 24126738
TI  - Practice Makes Perfect: Tips for Successful Institutional Review Board
      Submissions.

PMID- 24126739
TI  - Psychometric properties of a German parent rating scale for oppositional defiant
      and conduct disorder (FBB-SSV) in clinical and community samples.
AB  - The Fremdbeurteilungsbogen fur Storungen des Sozialverhaltens (FBB-SSV) is a
      commonly used DSM- and ICD-based rating scale for disruptive behaviour problems
      in Germany. This study examined the psychometric properties of the FBB-SSV rated
      by parents in both a clinical sample (N = 596) and a community sample (N = 720)
      of children aged 4-17 years. Results indicate that the FBB-SSV is internally
      consistent (alpha = .69-.90). Principal component analyses produced two-factor
      structures that are largely consistent with the distinction between oppositional
      defiant disorder (ODD) and conduct disorder (CD). Diagnostic accuracy was
      examined using receiver operating characteristic analyses, which showed that the
      FBB-SSV is excellent at discriminating children with ODD/CD from those in the
      community sample (AUC = .91). It has satisfactory diagnostic accuracy for
      detecting ODD/CD in the clinical sample (AUC = .76). Overall, the results show
      that the FBB-SSV is a reliable and valid instrument. This finding provides
      further support for the clinical utility of DSM- and ICD-based rating scales. 

PMID- 24126740
TI  - This special issue contains several papers on clinical trials, exemplifying Ross
      Prentice's influence. Preface.

PMID- 24126741
TI  - Epidermal growth factor enhances androgen receptor-mediated bladder cancer
      progression and invasion via potentiation of AR transactivation.
AB  - Androgen receptor (AR) plays a critical role in bladder cancer (BCa) development.
      Our early studies found AR knock-out mice (with few androgens and deleted AR)
      failed to develop BCa, yet 50% of castrated mice (with few androgens and existing
      AR) still developed BCa in an N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
      carcinogen-induced BCa mouse model, suggesting the existing AR in BCa of
      castrated mice may still play important roles in promoting BCa development at the
      castration level of androgens. The mechanism underlying this and/or which factors
      potentiate AR function at the castration level of androgen remains unclear.
      Epidermal growth factor (EGF), a key player in BCa progression, has been
      demonstrated to be able to potentiate AR transactivation in prostate cancer. In
      the present study, we found that EGF could increase BCa cell growth, migration
      and invasion in the presence of AR under the low amount of androgen and EGF was
      able to potentiate AR transactivation through EGFR by activating PI3K/AKT and
      MAPK pathway at castration androgen level. The increased suppression effects by
      EGFR inhibitor of PD168393 on AR function after addition of anti-androgen,
      Casodex, further suggested AR might play a key role in the effects of EGF on BCa
      progression and metastasis. Collectively, our results indicate that EGF may be
      able to potentiate AR transactivation that leads to enhancing BCa progression,
      which may help us to develop a better therapeutic approach to treat BCa via
      targeting both EGF and AR signaling. 

PMID- 24126742
TI  - Isolation and biological activities of an endophytic Mortierella alpina strain
      from the Antarctic moss Schistidium antarctici.
AB  - The Antarctic endophytic fungus (strain ITA1-CCMA 952) was isolated from the moss
      Schistidium antarctici found in Admiralty Bay, King George Island, Antarctica.
      Strain ITA1-CCMA 952 was assigned to the specie Mortierella alpina by
      phylogenetic analysis based on 18S rRNA gene sequences. This strain produces high
      levels of polyunsaturated fatty acids (PUFAs), including y-(gamma) linolenic acid
      and arachidonic acid, which when combined represents 48.3% of the total fatty
      acid content. Fungal extracts demonstrated strong antioxidant activity with the
      EC50 value of 48.7 MUg mL(-1) and also a strong antibacterial activity, mainly
      against the following bacteria: Escherichia coli, with a MIC of 26.9 MUg mL(-1)
      and Pseudomonas aeruginosa and Enterococcus faecalis, both with a MIC of 107 MUg
      mL(-1). A GC-MS analysis of the chloroform fraction obtained from the crude
      extract revealed the presence of potential antimicrobials (Pyrrolo[1,2-a]pyrazine
      1,4-dione, hexahydro-3-(2-methylpropyl) and Pyrrolo[1,2-a]pyrazine-1,4-dione,
      hexahydro-3-(phenylmethyl)) as the major compounds. Therefore, the M. alpina
      strain ITA1-CCMA 952 is a promising fungus for the biotechnological production of
      antibiotics, antioxidant substances and PUFAs. This study highlights the need for
      more research in extreme environments, such as Antarctica.

PMID- 24126743
TI  - Compensation of chief executive officers at nonprofit US hospitals.
AB  - IMPORTANCE: Hospital chief executive officers (CEOs) can shape the priorities and
      performance of their organizations. The degree to which their compensation is
      based on their hospitals' quality performance is not well known. OBJECTIVE: To
      characterize CEO compensation and examine its relation with quality metrics.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study.
      Participants included 1877 CEOs at 2681 private, nonprofit US hospitals. MAIN
      OUTCOMES AND MEASURES: We used linear regression to identify hospital structural
      characteristics associated with CEO pay. We then determined the degree to which a
      hospital's performance on financial metrics, technologic metrics, quality
      metrics, and community benefit in 2008 was associated with CEO pay in 2009.
      RESULTS: The CEOs in our sample had a mean compensation of $595,781 (median,
      $404,938) in 2009. In multivariate analyses, CEO pay was associated with the
      number of hospital beds overseen ($550 for each additional bed; 95% CI, 429-671;
      P < .001), teaching status ($425,078 more at major teaching vs nonteaching
      hospitals; 95% CI, 315,238-534,918; P < .001), and urban location. Hospitals with
      high levels of advanced technologic capabilities compensated their CEOs $135,862
      more (95% CI, 80,744-190,990; P < .001) than did hospitals with low levels of
      technology. Hospitals with high performance on patient satisfaction compensated
      their CEOs $51,706 more than did those with low performance on patient
      satisfaction (95% CI, 15,166-88,247; P = .006). We found no association between
      CEO pay and hospitals' margins, liquidity, capitalization, occupancy rates,
      process quality performance, mortality rates, readmission rates, or measures of
      community benefit. CONCLUSIONS AND RELEVANCE: Compensation of CEOs at nonprofit
      hospitals was highly variable across the country. Compensation was associated
      with technology and patient satisfaction but not with processes of care, patient
      outcomes, or community benefit.

PMID- 24126744
TI  - The New Zealand health system after 75 years: let's stop and smell the roses.

PMID- 24126745
TI  - Severe Clostridium difficile infection in New Zealand associated with an emerging
      strain, PCR-ribotype 244.
AB  - AIM: To compare disease severity and clinical outcome of Clostridium difficile
      infection (CDI) due to PCR-ribotype (RT) 244 with CDI due to other strains
      present in Auckland. METHOD: A retrospective, case-control study was conducted.
      Ten cases with CDI due to RT 244 were compared with 20 controls infected with
      other C. difficile strains. RT 244 isolates were further analysed for
      antimicrobial susceptibility, binary toxin genes and mutations in the tcdC gene.
      RESULTS: Cases were significantly more likely to have severe disease than
      controls (OR 9.33; p=0.015). 50% of cases had community-associated CDI compared
      with 15% of controls (p=0.078). All RT 244 isolates produced binary toxin and had
      a single-base pair deletion in tcdC at position 117. CONCLUSION: C. difficile RT
      244 is a newly recognised strain in New Zealand. It shares several features that
      characterise RT 027. Given its propensity to cause severe community-associated
      disease, a heightened awareness of this strain is needed to ensure early testing
      in patients admitted from the community with identified risk factors for CDI.

PMID- 24126746
TI  - Contribution by primary health nurses and general practitioners to the Diabetes
      Annual Review (Get Checked) programme in Auckland, New Zealand.
AB  - AIM: To describe primary health care (practice and specialist) nurses involvement
      in the government-funded annual diabetes review 'Get Checked' programme and the
      division of care between nurses and general practitioners in Auckland, New
      Zealand. METHOD: Of the total 911 practice and specialist nurses identified and
      working in the greater Auckland region, 276 (30%) were randomly selected and
      invited to undertake a self-administered questionnaire and telephone interview in
      2006-8. RESULTS: An 86% response rate was achieved. Over 60% of practice nurses
      and over half of specialist nurses participate in 'Get Checked' reviews. Of those
      nurses, 40% of practice and 70% specialist nurses, reported completing over half
      of the total number of 'Get Checked' reviews at their practice. Of the nurses
      sampled who work in general practice (n=198), 38% reported that 'nurses mostly
      complete' the reviews, 45% stated that 'nurses and doctors equally complete' them
      and 17% reported that only 'doctors' did so. For the nurses who reported that
      'nurses and doctors equally complete' the reviews (n=89), most nurses undertake
      blood pressure measurements (90%), weigh patients (88%), give lifestyle advice
      (87%), examine patient's feet (73%), and 44% carried out the complete review of
      the patients they consult. CONCLUSION: These findings show the 'Get Checked'
      programme was successful in engaging practice and community-based specialist
      nurses in the community management of diabetes and has revealed positive
      relationships between nurses and doctors, extended roles for nurses and the
      importance of engaging nurses in the design of health care programmes.

PMID- 24126747
TI  - Registered nurse assessment and treatment of skin sepsis in New Zealand schools:
      the development of protocols.
AB  - BACKGROUND: Skin infection is the commonest medical cause of hospitalisation in
      school children. Disadvantaged children, usually Maori or Pacific, have high
      rates of preventable diseases. AIM: To improve access to early treatment for skin
      infections using nurse-led school clinics in South Auckland, including provision
      of antibiotics under delegated standing orders. METHOD: Evidence-based protocols
      for the recognition and treatment of skin sepsis were developed following a
      literature search. A training package was developed for health professionals
      involved and outcome data were collected from a pilot study in which the
      protocols were trialled. RESULTS: An algorithm for diagnosis of skin infections
      was adapted from Steer et al (Bull World Health Organ. 2009;87:173-9). Fusidic
      acid ointment was recommended as first-line treatment for localised impetigo.
      Twice daily oral cephalexin was recommended for extensive impetigo and
      cellulitis, for palatability and simplicity of dosing. Fifty-six episodes of skin
      infection received treatment under standing orders in the first 15 weeks of the
      pilot study. CONCLUSION: Robust evidence to determine optimal choice, dosage and
      duration of antibiotic therapy for skin sepsis in children is lacking. The
      algorithms described are consistent with available evidence and provide a
      pragmatic approach for use in registered nurse (RN)-led school clinics.

PMID- 24126748
TI  - Malignant hypertension: a preventable emergency.
AB  - The Waitemata Hypertension Clinic Database 2009-2012 (Auckland, New Zealand) was
      searched for patients meeting the definition of Malignant Hypertension. Eighteen
      of 565 patients met the criteria. All patients had essential hypertension which
      was either undiagnosed, untreated or undertreated. Most cases responded
      satisfactorily to standard drug therapy, but a number were left with significant
      chronic kidney disease. Malignant hypertension is a life-threatening disease
      which should be entirely preventable with regular blood pressure checks in
      primary care. 

PMID- 24126749
TI  - Can we improve the prevention and detection of congenital abnormalities? An audit
      of early pregnancy care in New Zealand.
AB  - AIM: To determine whether there were "quality gaps" in the provision of care
      during pregnancies that resulted in a perinatal death due to congenital
      abnormality. METHOD: Perinatal deaths from congenital cardiovascular, central
      nervous system or chromosomal abnormality in 2010 were identified
      retrospectively. Data were extracted by retrospective clinical note review and
      obtained by independent review of ultrasound scans. RESULTS: There were 137
      perinatal deaths due to a congenital cardiovascular (35), central nervous system
      (29) or chromosomal abnormality (73). First contact with a health professional
      during pregnancy was predominantly with a general practitioner. First contact
      occurred within 14 weeks in 85% of pregnancies and there was often a significant
      delay before booking. Folate supplements were taken by 7% pre-conceptually and
      54% of women in the antenatal period. There were 20 perinatal deaths from neural
      tube defects that could potentially have been prevented through the use of pre
      conceptual folate. Antenatal screening was offered to 75% of the women who
      presented prior to 20 weeks and 84% of these undertook at least one of the
      available antenatal screening tests. Review of ultrasound images found five
      abnormalities could have been detected earlier. CONCLUSION: Delay in booking or
      failure to offer screening early were the most common reasons for delay in
      diagnosis of screen detectable abnormalities. The preventative value and timing
      of (pre-conceptual) folate needs emphasis.

PMID- 24126750
TI  - IgE-mediated food allergy--diagnosis and management in New Zealand children.
AB  - AIM: To summarise the diagnosis and management of IgE-mediated food allergy (FA)
      in New Zealand children. METHOD: A review of the scientific literature and
      subsequent consensus development. RESULTS: FA is a common problem in New Zealand
      children with management necessitating accurate diagnosis, appropriate risk
      management, and reassessment over time. CONCLUSION: This paper highlights the
      importance of a structured approach to diagnosis and management of FA in New
      Zealand children, guided by appropriately skilled health professionals.

PMID- 24126751
TI  - Questions about New Zealand's health system in 2013, its 75th anniversary year.
AB  - New Zealand's health system turns 75 in September, 2013. This article suggests
      that it is a time for celebration but also reflection on whether we have achieved
      the aims of the 1938 Social Security Act which laid out a set of principles for
      health care delivery. The article looks at questions of access, equity and
      service integration. It outlines why the health system we have today is shaped
      the way it is, and asks whether we should recommit to the original 1938 aims or
      develop a new set of principles for our health system. 

PMID- 24126752
TI  - Scalp involvement by Sarcoptes scabiei var hominis resembling seborrhoeic
      dermatitis in two immunocompromised patients with systemic lupus erythematosus.
AB  - Scabies is a common condition in New Zealand but scalp infestation by the mite is
      not often considered. Topical treatments traditionally do not involve the scalp.
      We report two cases of immunocompromised patients with systemic lupus
      erythematosus (SLE) who had scalp infestation clinically mimicking seborrhoeic
      dermatitis. 

PMID- 24126753
TI  - Medical image. A rare complication of cytarabine therapy.

PMID- 24126754
TI  - Medical image. Short metacarpal and metatarsals.

PMID- 24126755
TI  - Medical image. Systemic retinoids for recurrent keratoacanthomas.

PMID- 24126756
TI  - The legacy of Percy Pease.

PMID- 24126757
TI  - RMO patient safety forums in New Zealand: agents for change.

PMID- 24126760
TI  - CIZ1 regulates the proliferation, cycle distribution and colony formation of RKO
      human colorectal cancer cells.
AB  - Cip1-interacting zinc finger protein 1 (CIZ1) is a nuclear protein that was
      observed to bind to p21Cip1/Waf1. p21Cip1/Waf1 regulates the cell cycle and is
      associated with colorectal cancer (CRC) progression. However, the effect of CIZ1
      on CRC cells remains unclear. In the present study, CIZ1 was observed to be
      highly expressed in RKO human CRC cells. Silencing of CIZ1 using small
      interfering RNA (siRNA) suppressed RKO cell proliferation. Flow cytometric
      analysis demonstrated that knockdown of CIZ1 decreased the percentage of cells in
      the S phase and increased the ratio of cells in the G0/G1 phase in parallel with
      upregulated cell apoptosis. Moreover, the number and size of RKO cell colonies
      was repressed by knockdown of the CIZ1 gene. These results suggested that CIZ1
      may be involved in colon cancer progression by regulating cell proliferation,
      cell cycle, apoptosis and colony formation. Furthermore, CIZ1-siRNA may provide a
      novel tool for CRC investigation and therapy.

PMID- 24126759
TI  - The sex bias in systemic sclerosis: on the possible mechanisms underlying the
      female disease preponderance.
AB  - Systemic sclerosis is a multifactorial and heterogeneous disease. Genetic and
      environmental factors are known to interplay in the onset and progression of
      systemic sclerosis. Sex plays an important and determinant role in the
      development of such a disorder. Systemic sclerosis shows a significant female
      preponderance. However, the reason for this female preponderance is incompletely
      understood. Hormonal status, genetic and epigenetic differences, and lifestyle
      have been considered in order to explain female preponderance in systemic
      sclerosis. Sex chromosomes play a determinant role in contributing to systemic
      sclerosis onset and progression, as well as in its sex-biased prevalence. It is
      known, in fact, that X chromosome contains many sex- and immuno-related genes,
      thus contributing to immuno tolerance and sex hormone status. This review focuses
      mainly on the recent progress on epigenetic mechanisms--exclusively linked to the
      X chromosome--which would contribute to the development of systemic sclerosis.
      Furthermore, we report also some hypotheses (dealing with skewed X chromosome
      inactivation, X gene reactivation, acquired monosomy) that have been proposed in
      order to justify the female preponderance in autoimmune diseases. However,
      despite the intensive efforts in elucidating the mechanisms involved in the
      pathogenesis of systemic sclerosis, many questions remain still unanswered.

PMID- 24126758
TI  - Quantitative peripheral blood perturbations of gammadelta T cells in human
      disease and their clinical implications.
AB  - Human gammadelta T cells, which play innate and adaptive, protective as well as
      destructive, roles in the immune response, were discovered in 1986, but the
      clinical significance of alterations of the levels of these cells in the
      peripheral blood in human diseases has not been comprehensively reviewed. Here,
      we review patterns of easily measurable changes of this subset of T cells in
      peripheral blood from relevant publications in PubMed and their correlations with
      specific disease categories, specific diagnoses within disease categories, and
      prognostic outcomes. These collective data suggest that enumeration of gammadelta
      T cells and their subsets in the peripheral blood of patients could be a useful
      tool to evaluate diagnosis and prognosis in the clinical setting. 

PMID- 24126762
TI  - Molecular fossils probe life's origins. Research into molecular fossils and
      modern viruses is shedding light on the evolution of archaea, prokaryotes and
      eukaryotes.

PMID- 24126761
TI  - hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance
      of genome integrity.
AB  - Prim-pol is a recently identified DNA primase-polymerase belonging to the
      archaeao-eukaryotic primase (AEP) superfamily. Here, we characterize a previously
      unrecognized prim-pol in human cells, which we designate hPrimpol1 (human primase
      polymerase 1). hPrimpol1 possesses primase and DNA polymerase activities in
      vitro, interacts directly with RPA1 and is recruited to sites of DNA damage and
      stalled replication forks in an RPA1-dependent manner. Cells depleted of
      hPrimpol1 display increased spontaneous DNA damage and defects in the restart of
      stalled replication forks. Both RPA1 binding and the primase activity of
      hPrimpol1 are required for its cellular function during DNA replication. Our
      results indicate that hPrimpol1 is a novel factor involved in the response to DNA
      replication stress. 

PMID- 24126764
TI  - Toward a role model.

PMID- 24126763
TI  - Nucleosome sliding by Chd1 does not require rigid coupling between DNA-binding
      and ATPase domains.
AB  - Chromatin remodellers are ATP-dependent motor proteins that physically reposition
      and reorganize nucleosomes. Chd1 and Iswi-type remodellers possess a DNA-binding
      domain (DBD) needed for efficient nucleosome mobilization; however, it has not
      been clear how this domain physically contributes to remodelling. Here we show
      that the Chd1 DBD promotes nucleosome sliding simply by tethering the remodeller
      to nucleosome substrates. Nucleosome sliding activity was largely resistant to
      increasing length and flexibility of the linker connecting the DBD and ATPase
      motor, arguing that the ATPase motor does not shift DNA onto the nucleosome by
      pulling on the DBD. 

PMID- 24126765
TI  - Bone complications in patients with Cushing's syndrome: looking for clinical,
      biochemical, and genetic determinants.
AB  - SUMMARY: This is the first study examining the impact of both clinical,
      biochemical, and genetic determinants in the occurrence of bone complications in
      patients with overt Cushing's syndrome (CS). It demonstrates that the degree and
      duration of hypercortisolism seem to play a major role in bone loss and fractures
      development in these patients. INTRODUCTION: Bone loss and fractures are a common
      complication of CS. We investigate the role of gender, disease etiology,
      duration, and degree of hypercortisolism as well as the impact of glucocorticoid
      receptor (GR) polymorphisms on the development of bone complications in CS.
      METHODS: Fifty-two patients with active CS (38 Cushing's disease and 14 with
      cortisol-secreting adrenal adenoma) were genotyped for GR polymorphisms (BclI,
      N363S, ER22/23EK, and A3669G). In all patients, clinical, hormonal, and
      biochemical markers of bone turnover, densitometric parameters [lumbar spine and
      left femur bone mineral density (BMD), T-score, Z-score] as well as the
      prevalence of bone demineralization and both vertebral and peripheral fractures
      were assessed. RESULTS: No differences were found in bone complications according
      to gender, disease etiology, and genetic variants distribution. Fractured
      patients compared to non-fractured ones showed increased levels of urinary free
      cortisol (UFC) and a more compromised densitometric profile. UFC levels
      correlated with the occurrence of vertebral fractures (r = 0.43, p = 0.009) while
      midnight serum cortisol correlated with L1-L4 BMD values (r = -0.35, p = 0.04).
      Disease duration correlated with the presence of peripheral fractures (r = 0.36,
      p = 0.04). CONCLUSIONS: While GR gene variants as well as gender and disease
      etiology seem not to play a role, the degree and duration of hypercortisolism
      seem to be the major determinants of bone loss and fractures in this group of
      patients. More investigations are needed to understand the real impact of these
      determinants on the development of bone complications in patients with
      hypercortisolism.

PMID- 24126766
TI  - Serum vitamin D and C-reactive protein levels are independently associated with
      diastolic dysfunction.
AB  - BACKGROUND AND AIM: Vitamin D deficiency is common and may contribute to
      cardiovascular diseases. We hypothesized that serum 25-hydroxyvitamin D [25(OH)D]
      levels would be inversely associated with inflammation and with diastolic
      dysfunction. We therefore investigated the link between serum vitamin D levels
      (i) echocardiographic measures and (ii) inflammatory parameters. METHODS: The
      cross-sectional study included 281 patients who were referred to coronary
      angiography for stable angina pectoris. Patients were recruited between December
      2010 and November 2011. Patients with established congestive heart failure, gout,
      chronic kidney disease (estimated glomeruler filtration rate <60 mL/min per 1.73
      m), and acute infection were not included. We measured serum 25(OH)D levels, C
      reactive protein and fibrinogen levels. A radioimmunoassay procedure was used to
      measure 25(OH)D (DiaSorin, Stillwater, MN). We also performed standardized left
      ventricular (LV) echocardiograms, and echocardiographic data were used for
      classification of systolic and diastolic dysfunction. We analyzed the relation
      between serum levels of 25(OH)D and inflammatory markers and echocardiographic
      measures of LV mass and diastolic dysfunction. RESULTS: At baseline, subjects had
      a mean age of 59.5 +/- 10 years, and 43.4% were women. Left ventricular mass
      index, left atrial diameter, isovolumic relaxation time, and E/E' ratio were
      significantly higher in patients with lower 25(OH)D levels. In ordinal logistic
      regression analysis, higher 25(OH)D was negatively associated only with LV mass
      index (odds ratio [OR], 0.965; 95% confidence interval [95% CI], 0.939-0.992; P =
      0.015), isovolumic relaxation time (OR, 0.962; 95% CI, 0.939-0.985; P = 0.001),
      E/E' ratio (OR, 0.874; 95% CI, 0.811-0.942; P = 0.008), and C-reactive protein
      (OR, 0.802; 95% CI, 0.668-0.962; P = 0.021). CONCLUSIONS: Serum levels of 25(OH)D
      are significantly associated with LV diastolic dysfunction and LV mass index,
      although the effect size is rather small. Longitudinal studies in larger
      populations are needed to establish firmly or refute a causal relationship
      between vitamin D levels and diastolic dysfunction and LV mass index.

PMID- 24126767
TI  - The relationship between platelet collagen receptor glycoprotein VI and no-reflow
      phenomenon in patients with acute ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to determine whether admission soluble
      glycoprotein VI (sGP-VI) level is associated with no-reflow phenomenon (NRP)
      after primary percutaneous coronary intervention (P-PCI) in patients with acute
      ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 178
      consecutive patients admitted to our hospital for a first STEMI and undergoing P
      PCI within 12 hours of onset of symptoms were enrolled. The patients were divided
      into 2 groups (NRP group and reflow group). Admission sGP-VI plasma levels were
      measured by enzyme-linked immunosorbent assay. RESULTS: Of the 178 patients who
      underwent P-PCI, 41 patients (23%) developed NRP. The patients in the reflow
      group had higher levels of sGP-VI compared with the patients in the NRP group
      (38.5 +/- 21.0 vs 21.9 +/- 11.9 ng/mL, P < 0.001). The sensitivity and
      specificity values of the sGP-VI levels were 90% and 49%, respectively (cutoff
      value was <= 25). In the multivariate logistic regression analyses, sGP-VI levels
      of 25 ng/mL or lower, higher peak troponin T levels and body mass index value,
      amount of opaque of greater than 250 mL, and lesion length of greater than 13.5
      mm were independent predictors of angiographic NRP. CONCLUSIONS: Lower admission
      sGP-VI levels are associated with NRP in patients with STEMI undergoing P-PCI.
      This outcome may open new therapeutic facility in the setting of P-PCI.

PMID- 24126771
TI  - Do physicians have an obligation to disclose the uncertainty about harms or just
      the harms?

PMID- 24126768
TI  - Change in DASH diet score and cardiovascular risk factors in youth with type 1
      and type 2 diabetes mellitus: The SEARCH for Diabetes in Youth Study.
AB  - Youth with diabetes are at an increased risk of cardiovascular disease (CVD).
      Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has been
      shown to improve CVD risk. In this study, we evaluated whether changes in diet
      quality as characterized by DASH are associated with changes in CVD risk factors
      in youth with diabetes over time. Longitudinal mixed models were applied to data
      from 797 participants in the SEARCH for Diabetes in Youth Study representing
      three time points: baseline, 12- and 60-month follow-up. Data were restricted to
      youth whose diabetes was first diagnosed in 2002-2005. DASH-related adherence was
      poor and changed very little over time. However, an increase in DASH diet score
      was significantly associated with a decrease in HbA1c levels in youth with type 1
      diabetes (beta=-0.20, P-value=0.0063) and a decrease in systolic blood pressure
      among youth with type 2 diabetes (beta=-2.02, P-value=0.0406). Improvements in
      dietary quality may be beneficial in youth with type 1 or type 2 diabetes.
      However, further work in larger groups of youth with type 1 and 2 diabetes is
      desirable. 

PMID- 24126772
TI  - Variability in vitamin D content among products for multivitamin and mineral
      supplements.

PMID- 24126773
TI  - Do physicians have an obligation to disclose the uncertainty about harms or just
      the harms?--Reply.

PMID- 24126774
TI  - The inferior vena cava filter.

PMID- 24126775
TI  - The inferior vena cava filter.

PMID- 24126776
TI  - The inferior vena cava filter.

PMID- 24126777
TI  - The inferior vena cava filter--reply.

PMID- 24126778
TI  - Toward electronic medical record alerts that consume less physician time.

PMID- 24126782
TI  - Toward electronic medical record alerts that consume less physician time--reply.

PMID- 24126783
TI  - IGF-1 gene-modified muscle-derived stem cells are resistant to oxidative stress
      via enhanced activation of IGF-1R/PI3K/AKT signaling and secretion of VEGF.
AB  - Reactive oxygen species (ROS)-induced oxidative stress increases in skeletal
      muscle with aging and decreases the viability of implanted cells. Type 1 insulin
      like growth factor (IGF-1) promotes the survival of skeletal muscle cells under
      oxidative stress. It is unknown whether IGF-1 protects muscle-derived stem cells
      (MDSCs) from oxidative stress. In this study, we genetically engineered rat MDSCs
      to overexpress IGF-1 and determined cell viability, apoptosis, and VEGF secretion
      under oxidative stress. Overexpression of IGF-1 prevented MDSCs from H2O2-induced
      caspase-dependent apoptotic cell death by upregulating the PI3K/AKT pathway,
      accompanied with an increase of NF-kappaB, p-NF-kappaB, Bcl-2, and VEGF, as well
      as a decrease of Bax. In contrast, pre-administration of picropodophyllinb,
      wortmannin, 1L-6-hydroxymethyl-chiro-inositol-2-((R)-2-O-methyl-3-O
      octadecylcarbonate), or pyrrolidine-dithiocarbamate, specific inhibitors of IGF
      1R, PI3K, AKT, and NF-kappaB, respectively, followed by treatment with H2O2,
      resulted in cell death of MDSCs. Our data indicated that IGF-1 suppresses
      apoptosis and enhances the paracrine function of MDSCs under oxidative stress via
      enhancing IGF-1R/PI3K/AKT signaling. Thus, IGF-1 gene-modified MDSCs present a
      potential application in the treatment of muscle wasting, such as urethra
      intrinsic sphincter deficiency. 

PMID- 24126784
TI  - Silencing Pax3 by shRNA inhibits the proliferation and differentiation of duck
      (Anas platyrhynchos) myoblasts.
AB  - The Pax3 gene has been proven to play a crucial role in determining myogenic
      progenitor cell fate during embryonic myogenesis; however, the molecular role of
      Pax3 in myoblast development during later stages of myogenesis is unknown. We
      hypothesized that Pax3 would function in myoblast proliferation and
      differentiation; therefore, we employed three short hairpin RNAs (shRNAs)
      (shRNA1, shRNA2, and shRNA3) that target Pax3 to characterize the function of
      Pax3 in duck myoblast development. The mRNA and protein expression levels of Pax3
      in duck myoblasts were detected using real-time PCR and Western blotting. Cell
      proliferation was assessed using the MTT and BrdU assays, while cell
      differentiation was assayed using immunofluorescence labeling with a MyoG
      antibody. Additionally, folic acid (FA), which is a rescue tool, was added into
      the medium of duck myoblasts to indirectly examine the function of Pax3 on duck
      myoblast proliferation and differentiation. The results revealed that one of the
      shRNA vectors, shRNA1, could significantly and stably reduce the expression of
      Pax3 (P < 0.05). Silencing Pax3 by shRNA1 significantly reduced the proliferation
      and differentiation of duck myoblasts (P < 0.05) due to downregulated expression
      of myogenic regulator factors. These trends could be rescued by adding FA; and
      Pax7, a paralog gene of Pax3, was involved in those processes. Overall, Pax3 had
      a positive function in duck myoblast proliferation and differentiation by
      modulating the expression of myogenic regulation factors, and shRNA targeting of
      Pax3 might be a new approach for understanding the function of Pax3 in the
      development of diverse tissues. 

PMID- 24126785
TI  - Statins in pregnancy.
AB  - PURPOSE OF REVIEW: The use of statins in women of reproductive age to prevent
      adverse cardiovascular events is on the rise. This is attributed to an increase
      in metabolic risk factors such as obesity, raised lipids, diabetes and high blood
      pressure. Statins are contraindicated in pregnancy because of the perceived
      increased risk of congenital abnormalities to the foetus. We evaluated the
      evidence, including published reviews and primary studies, on the safety of
      statins in pregnancy and assessed the benefits to the mother. RECENT FINDINGS:
      The risk of major congenital abnormalities from exposure to statins in pregnancy
      is similar to the background risk of the population. No specific pattern of
      abnormalities was observed. Existing studies are small with limitations in their
      quality. Preliminary evidence suggests a beneficial role for statins in
      preventing preeclampsia. SUMMARY: There is no evidence to demonstrate that use of
      statins in pregnancy increases the risk of foetal abnormalities. The findings
      were limited by the poor quality and reporting of existing studies.

PMID- 24126786
TI  - Stroke during pregnancy and pre-eclampsia.
AB  - PURPOSE OF REVIEW: Stroke is a life-threatening condition whose frequency is
      increased during pregnancy, in particular in the two first weeks of the
      puerperium. Pre-eclampsia/eclampsia is a disorder that enhances this risk. The
      purpose of this review is to summarize existing data regarding the association,
      diagnosis as well as management for stroke in pre-eclampsia or eclampsia. RECENT
      FINDINGS: In about one third of stroke cases during pregnancy or puerperium, pre
      eclampsia or eclampsia is concomitantly diagnosed. In these women, hemorrhagic
      stroke is more common than ischemic stroke, probably as a result of severe
      hypertension. Clinical presentation may vary but severe headache is the most
      common symptom. Neuroimaging techniques are warranted to identify affected cases.
      Prevention is based on blood pressure adjustment and thromboprophylaxis. SUMMARY:
      The risk of stroke should be taken into consideration in women with a diagnosis
      of pre-eclampsia or eclampsia. In particular, women with neurologic symptoms
      should be promptly evaluated, blood pressure should be adjusted and
      thromboprophylaxis should be started.

PMID- 24126787
TI  - Cost-effectiveness analyses and their role in improving healthcare strategies.
AB  - PURPOSE OF REVIEW: In this era of healthcare reform, attention is focused on
      increasing the quality of care and access to services, while simultaneously
      reducing the cost. Economic evaluations can play an important role in translating
      research to evidence-based practice and policy. RECENT FINDINGS: Cost
      effectiveness analysis (CEA) and its utility for clinical and policy decision
      making among U.S. obstetricians and gynecologists is reviewed. Three case
      examples demonstrating the value of this methodology in decision making are
      considered. A discussion of the methodologic principles of CEA, the advantages,
      and the limitations of the methodology are presented. SUMMARY: CEA can play an
      important role in evidence-based decision making, with value for clinicians and
      policy makers alike. These studies are of particular interest in the field of
      obstetrics and gynecology, in which uncertainty from epidemiologic or clinical
      trials exists, or multiple perspectives need to be considered (maternal,
      neonatal, and societal). As with all research, it is essential that economic
      evaluations are conducted according to established methodologic standards.
      Interpretation and application of results should occur with a clear understanding
      of both the value and the limitations of economic evaluations.

PMID- 24126788
TI  - The environment as a strategic healthcare partner.
AB  - PURPOSE OF REVIEW: To describe the growing-consensus opinion regarding the
      contribution of natural processes - 'nature' - to human health. Globally, natural
      environments are becoming smaller and critically degraded because of various
      human-related factors. Consequently, some of the 'free' health benefits nature
      confers are being lost. This is especially problematic for people in rural areas
      with limited access to clinical services whose lives depend closely upon nature.
      RECENT FINDINGS: In 2001, an assessment of the world's 'ecosystems' was initiated
      - the Millennium Ecosystem Assessment. It explored ecosystem changes and their
      subsequent effects in various locales on human well being, including health.
      Global Burden of Disease studies have also revealed the importance of
      environmental factors to health, in some countries in particular. Not
      coincidentally, geographic areas in the two research efforts overlap. Despite
      this, convincing research describing how conserving healthy environments may
      positively affect human health remains lacking. SUMMARY: Establishing ecosystem
      human health causal linkages via traditional epidemiological approaches is
      challenging. Innovative research initiatives are beginning to increase our
      understanding and appreciation of nature's role as a provider of health,
      rendering conservation potentially a healthcare strategy. Transdisciplinary
      university teaching is also playing a role in broadening the awareness of these
      important linkages and developing research skills to meet the challenge.

PMID- 24126789
TI  - A high-sensitivity near-infrared phototransistor based on an organic bulk
      heterojunction.
AB  - High-gain photodetectors with near-infrared (NIR) sensitivity are critical for
      biomedical applications such as photoplethysmography and optical coherence
      tomography where detected optical signals are relatively weak. Current
      photodetection technologies rely on avalanche photodiodes and photomultipliers to
      achieve high sensitivity. These devices, however, require a high operation
      voltage and are not compatible with CMOS based read-out circuits (ROCs). In this
      work we demonstrate a solution-proceeded NIR phototransistor structure based on a
      bulk heterojunction (BHJ) of a narrow bandgap polymer, poly(N-alkyl diketopyrrolo
      pyrrole dithienylthieno[3,2-b]thiophene) (DPP-DTT), and [6,6]-phenyl-C61-butyric
      acid methylester (PCBM). The device exhibits ultrahigh responsivity (~5 * 10(5) A
      W(-1)) as well as wide tunability (>1 * 10(4)) of photoconductive gain. Using the
      current-voltage and transient photocurrent measurements we show that the high
      responsivity is due to the combined effects of fast transport of holes in the
      polymer matrix and slow detrapping of electrons from the isolated PCBM domains.
      The wide gain tunability and the efficient suppression of noise current are
      achieved through the use of the optically tunable gate terminal. We demonstrate
      that our phototransistor can be used as the detection unit in a
      photoplethysmography sensor for non-invasive, continuous finger pulse wave
      monitoring. The high-sensitivity of the phototransistor allows the use of a low
      power light source, thus reducing the overall power consumption of the sensor.
      This, together with the solution processibility and the simple device
      configuration (which is compatible with conventional ROCs), make the
      phototransistor a very promising component for the next generation low-cost,
      mobile biomedical devices for health monitoring and remote diagnostics. 

PMID- 24126790
TI  - How long do I have?

PMID- 24126791
TI  - Activation of estrogen receptors with E2 downregulates peroxisome proliferator
      activated receptor gamma in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and
      occurs more often in men than in women; however, little is known about its
      underlying molecular mechanisms. The present study investigated the effect of
      estrogen receptor (ER)alpha and ERbeta on peroxisome proliferator-activated
      receptor gamma (PPARgamma) expression in Hep3B cells. We examined PPARgamma,
      ERalpha and ERbeta mRNA and protein expression by RT-PCR and western blotting. In
      order to determine whether PPARgamma plays a central role in HCC, we screened for
      PPARgamma expression in liver cancer patient tissues and differentially
      differentiated HCC cell lines (HA22T, Huh-7, Hep3B and HepG2). We found that
      PPARgamma expression was highly expressed in liver cancer tissues and in Hep3B
      cells. Furthermore, overexpression of ERalpha and ERbeta was found to decrease
      PPARgamma expression at the transcriptional as well as at the translational level
      in a ligand-dependent manner. In summary, the present study demonstrated that
      both ERalpha and beta were sufficient to inhibit PPARgamma and provide a valuable
      therapeutic option for the treatment of HCC patients.

PMID- 24126792
TI  - Crystal structure of the Psb28 accessory factor of Thermosynechococcus elongatus
      photosystem II at 2.3 A.
AB  - Members of the Psb28 family of proteins are accessory factors implicated in the
      assembly and repair of the photosystem II complex. We present here the crystal
      structure of the Psb28 protein (Tlr0493) found in the thermophilic cyanobacterium
      Thermosynechococcus elongatus at a resolution of 2.3 A. Overall the crystal
      structure of the Psb28 monomer is similar to the solution structures of C
      terminally His-tagged Psb28-1 from Synechocystis sp. PCC 6803 obtained previously
      by nuclear magnetic resonance spectroscopy. One new aspect is that Escherichia
      coli-expressed T. elongatus Psb28 is able to form dimers in solution and packs as
      a dimer of dimers in the crystal. Analysis of wild type and mutant strains of
      Synechocystis 6803 by blue native-polyacrylamide gel electrophoresis suggests
      that Psb28-1, the closest homologue to T. elongatus Psb28 in this organism, also
      exists as an oligomer in vivo, most likely a dimer. In line with the prediction
      based on the crystal structure of T. elongatus Psb28, the addition of a 3* Flag
      tag to the C-terminus of Synechocystis 6803 Psb28-1 interferes with the
      accumulation of the Psb28-1 oligomer in vivo. In contrast, the more distantly
      related Psb28-2 protein found in Synechocystis 6803 lacks the residues that
      stabilize dimer formation in the T. elongatus Psb28 crystal and is detected as a
      monomer in vivo. Overall our data suggest that the dimer interface in the Psb28
      crystal might be physiologically relevant. 

PMID- 24126793
TI  - Identification of specific reversal agents for Leishmania ABCI4-mediated antimony
      resistance by flavonoid and trolox derivative screening.
AB  - OBJECTIVES: To identify reversal agents for the Leishmania ABCI4 transporter that
      confers resistance to antimony. METHODS: Selective ABCI4 inhibitors among a
      series of 15 flavonoid and trolox derivatives or analogues were investigated by
      evaluating their ability to reverse antimony resistance in Leishmania parasites
      overexpressing ABCI4. Among the compounds screened, N-ethyltrolox carboxamide
      (compound D2) produced the highest reversal activity. In order to optimize the
      activity of D2, we synthesized a series of 10 derivatives by condensation of
      various amines with trolox. RESULTS: Analysis of antimony resistance reversal
      activity showed that N-propyltrolox carboxamide (compound D4) was the most potent
      ABCI4 inhibitor, with reversal activity being maintained in the intracellular
      amastigote stage. In addition, trolox derivatives significantly reverted the
      resistance to zinc protoporphyrin. The mechanism of action of these active
      derivatives was found to be related to significant reversion of Sb(III) and zinc
      protoporphyrin accumulation and to a decrease in drug efflux. CONCLUSIONS: Our
      findings suggest that trolox derivatives D2 and D4 could be considered to be
      specific reversal agents targeting the Leishmania ABCI4 transporter. The
      structure-activity relationship obtained in the present study highlights the
      importance of the size and length of the alkyl substituent linked to trolox.
      Furthermore, the structural data obtained provide valuable information for the
      further development of new, even more specific and potent Leishmania ABCI4
      reversal agents.

PMID- 24126794
TI  - Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in
      preventing malaria in pregnancy: the potential of 5-methyl-tetrahydrofolate.
AB  - Malaria remains the leading cause of mortality and morbidity in children under
      the age of 5 years and pregnant women. To counterbalance the malaria burden in
      pregnancy, an intermittent preventive treatment strategy has been developed. This
      is based on the use of the antifolate sulfadoxine/pyrimethamine, taken at
      specified intervals during pregnancy, and reports show that this approach reduces
      the malaria burden in pregnancy. Pregnancy is also associated with the risk of
      neural tube defects (NTDs), especially in women with low folate status, and folic
      acid supplementation is recommended in pregnancy to lower the risk of NTDs. Thus,
      in malaria-endemic areas, pregnant women have to take both antifolate medication
      to prevent malaria and folic acid to lower the risk of NTDs. However, the
      concomitant use of folate and antifolate is associated with a decrease in
      antifolate efficacy, exposing pregnant women to malaria. Thus, there is genuine
      concern that this strategy may not be appropriate. We have reviewed work carried
      out on malaria folate metabolism and antifolate efficacy in the context of folate
      supplementation. This review shows that: (i) the folate supplementation effect on
      antifolate efficacy is dose-dependent, and folic acid doses required to protect
      pregnant women from NTDs will not decrease antifolate activity; and (ii) 5-methyl
      tetrahydrofolate, the predominant form of folate in the blood circulation, could
      be administered (even at high dose) concomitantly with antifolate without
      affecting antifolate efficacy. Thus, strategies exist to protect pregnant women
      from malaria while maintaining adequate folate levels in the body to reduce the
      occurrence of NTDs. 

PMID- 24126795
TI  - Selective deprotonation of oxazole and photoelectron imaging of the oxazolide
      anion.
AB  - A photoelectron imaging study of the oxazolide anion obtained by selective
      deprotonation of oxazole at the C2 position is reported. The photodetachment
      transitions observed at 355, 392, and 532 nm are assigned to the ground state of
      the neutral oxazolyl sigma radical. A Franck-Condon analysis of this transition
      aids in the first determination of the adiabatic electron affinity of oxazolyl,
      EA = 2.21 +/- 0.02 eV. A vibrational progression with a frequency of 890 +/- 80
      cm(-1) is observed, corresponding to an in-plane ring distortion mode. The
      photoelectron angular distributions are analyzed using the mixed s-p model,
      shedding light on the hybrid character of the anion HOMO. 

PMID- 24126796
TI  - Predicting utility scores for prostate cancer: mapping the Prostate Cancer Index
      to the Patient-Oriented Prostate Utility Scale (PORPUS).
AB  - BACKGROUND: The Prostate Cancer Index (PCI) is a health profile instrument that
      measures health-related quality of life with six subscales: urinary, sexual, and
      bowel function and bother. The Patient-Oriented Prostate Utility Scale (PORPUS-U)
      measures utility (0=dead and 1=full health). Utility is a preference-based
      approach to measure health-related quality of life, required for decision
      analyses and cost-effectiveness analyses. We developed a function to estimate
      PORPUS-U utilities from PCI scores. METHODS: The development data set included
      676 community-dwelling prostate cancer (PC) survivors who completed the PCI and
      PORPUS-U by mail. We fit three linear regression models: one used original PORPUS
      U scores and two used log-transformed PORPUS-U scores, one with a hierarchy
      constraint and one without. The model selection was performed using stepwise
      selection and fivefold cross validation. The validation data included 248 PC
      outpatients with three assessments on the PCI and PORPUS-U. Scores were
      retransformed for validation, with Duan's smearing estimator applied to correct
      potential bias. The predictive ability of the models was assessed with R(2), root
      mean square error (RMSE) and by comparing predicted and observed utilities.
      RESULTS: The best-fitting model used the log-transformed PORPUS-U with no
      hierarchy constraint. The R(2) was 0.72. The RMSE ranged from 0.040 to 0.061 for
      the three validation data sets. Differences between predicted and observed
      utilities ranged from 0.000 to 0.006 but predicted utilities overestimated the
      lowest 5% of observed PORPUS-U scores and underestimated the highest observed
      scores. CONCLUSIONS: Our algorithm can calculate PORPUS-U utility scores from PCI
      scores, thus supplementing descriptive quality of life measures with utility
      scores in PC patients. Utilities derived from mapping algorithms are useful for
      assigning utility to groups of patients but are less accurate at predicting
      utility of individual patients. We are exploring statistical methods to improve
      the mapping of utilities from descriptive instruments.

PMID- 24126797
TI  - Performance of multiparametric MRI in men at risk of prostate cancer before the
      first biopsy: a paired validating cohort study using template prostate mapping
      biopsies as the reference standard.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has the potential
      to serve as a non-invasive triage test for men at risk of prostate cancer. Our
      objective was to determine the performance characteristics of mpMRI in men at
      risk before the first biopsy using 5 mm template prostate mapping (TPM) as the
      reference standard. METHODS: One hundred and twenty-nine consecutive men with
      clinical suspicion of prostate cancer, who had no prior biopsy, underwent mpMRI
      (T1/T2-weighted, diffusion-weighting, dynamic contrast enhancement) followed by
      TPM. The primary analysis used were as follows: (a) radiological scores of
      suspicion of >=3 attributed from a five-point ordinal scale, (b) a target
      condition on TPM of any Gleason pattern >=4 and/or a maximum cancer core length
      of >=4 mm and (c) two sectors of analysis per prostate (right and left prostate
      halves). Secondary analyses evaluated the impact of changing the mpMRI score
      threshold to >=4 and varying the target definition for clinical significance.
      RESULTS: One hundred and forty-one out of 258 (55%) sectors of analysis showed
      'any cancer' and 77/258 (30%) had the target histological condition for the
      purpose of deriving the primary outcome. Median (with range) for age, PSA, gland
      volume and number of biopsies taken were 62 years (41-82), 5.8 ng ml(-1) (1.2
      20), 40 ml (16-137) and 41 cores (20-93), respectively. For the primary outcome
      sensitivity, specificity, positive and negative predictive values and area under
      the receiver-operating curve (with 95% confidence intervals) were 94% (88-99%),
      23% (17-29%), 34% (28-40%), 89% (79-98%) and 0.72 (0.65-0.79), respectively.
      CONCLUSIONS: MpMRI demonstrated encouraging diagnostic performance
      characteristics in detecting and ruling out clinically significant prostate
      cancer in men at risk, who were biopsy naive.

PMID- 24126799
TI  - Developing regulatory strategy for microbicides.
AB  - Ever since the discovery that a virus was responsible for AIDS, prevention of HIV
      infection has been a drug/vaccine development target in therapeutic research.
      Microbicide products are a viable, globally applicable option; however, to date,
      no product has been approved anywhere in the world. Development of such a product
      will need to account for the changing disease landscape and will need to leverage
      available regulatory pathways to gain approvals in the developed world and
      emerging markets. In countries where the regulatory pathway is not clear which is
      the case in several emerging markets, sponsors will need to employ a flexible
      approach to gather and meet local regulatory requirements and ultimately gain
      product approvals. 

PMID- 24126798
TI  - Third-line rescue therapy with bismuth-containing quadruple regimen after failure
      of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.
AB  - BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor
      (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy
      with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To
      evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen
      in patients with two consecutive eradication failures. METHODS: Prospective
      multicenter study of patients in whom 1st treatment with PPI-clarithromycin
      amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd
      eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth
      subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to
      500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.).
      Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy.
      Compliance was determined through questioning and recovery of empty medication
      envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS:
      Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 %
      uninvestigated-functional dyspepsia) were initially included, and two were lost
      to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol
      and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58
      72 %). Adverse effects were reported in 22 % of patients, the most common being
      nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %),
      none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an
      acceptable third-line strategy and a safe alternative after two previous H.
      pylori eradication failures with standard clarithromycin- and levofloxacin
      containing triple therapies.

PMID- 24126800
TI  - The role of epithelial mesenchymal transition markers in thyroid carcinoma
      progression.
AB  - Understanding the molecular mechanisms involved in thyroid cancer progression may
      provide targets for more effective treatment of aggressive thyroid cancers.
      Epithelial mesenchymal transition (EMT) is a major pathologic mechanism in tumor
      progression and is linked to the acquisition of stem-like properties of cancer
      cells. We examined expression of ZEB1 which activates EMT by binding to the E-box
      elements in the E-cadherin promoter, and expression of E-cadherin in normal and
      neoplastic thyroid tissues in a tissue microarray which included 127 neoplasms
      and 10 normal thyroid specimens. Thyroid follicular adenomas (n = 32), follicular
      thyroid carcinomas (n = 28), and papillary thyroid carcinomas (n = 57) all
      expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic
      thyroid carcinomas (ATC, n = 10) were negative for E-cadherin, but positive for
      ZEB1. A validation set of 10 whole sections of ATCs showed 90 % of cases positive
      for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines
      (normal thyroid, NTHY-OR13-1; PTC, TPC-1, and ATC, THJ-21T) showed that the ATC
      cell line expressed the highest levels of ZEB1 while the normal thyroid cell line
      expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed
      that Smad7 mRNA was significantly higher in ATC than in any other group (p <
      0.05). These results indicate that ATCs show evidence of EMT including decreased
      expression of E-cadherin and increased expression of ZEB1 compared to well
      differentiated thyroid carcinomas and that increased expression of Smad7 may be
      associated with thyroid tumor progression. 

PMID- 24126801
TI  - Osteoprotegerin promotes the proliferation of chondrocytes and affects the
      expression of ADAMTS-5 and TIMP-4 through MEK/ERK signaling.
AB  - The involvement of osteoprotegerin (OPG) in bone metabolism has previously been
      established; however, whether OPG regulates chondrocytes directly and exerts
      precise cellular and molecular effects on chondrocytes remains to be determined.
      Thus, the present study aimed to investigate the direct effect of OPG on the
      viability, proliferation and functional consequences of chondrocytes. Primary
      chondrocytes were isolated from the knee of Sprague-Dawley rats. Passage 1
      chondrocytes were identified by toluidine blue staining and used in the
      experiments. The cell proliferation induced by OPG at various concentrations was
      measured by a Cell Counting kit-8 (CCK-8) assay. Following pretreatment with
      mitogen-activated/extracellular signal-regulated kinase kinase (MEK) inhibitor
      U0126, extracellular signal-regulated kinase (ERK) inhibitor PD098059, and P38
      mitogen-activated protein kinase (P38MAPK) inhibitor SB203580 for 30 min,
      chondrocytes were treated with OPG, and CCK-8 was performed. The cellular signals
      of MAPKs, including ERK, P38MAPK and c-Jun N-terminal protein kinase (JNK), were
      investigated by western blot analysis following treatment with OPG. The
      functional consequences following treatment with soluble OPG were analyzed by
      qPCR and western blot analysis. OPG increased chondrocyte proliferation with
      maximal effect at 10 ng/ml, and induced the phosphorylation of MEK and ERK but
      not P38MAPK or JNK. Suppression of ERK activity via PD098095 inhibited OPG
      induced chondrocyte proliferation. Administration of OPG significantly
      downregulated ADAMTS-5 and upregulated tissue inhibitor of metalloproteinase
      (TIMP)-4 production, but had no effect on the expression of TIMP-1, -2 and -3,
      insulin-like growth factor I, transforming growth factor-beta, basic fibroblast
      growth factor, bone morphogenetic protein-2, collagen II, aggrecan and ADAMTS-4.
      Suppression of ERK activity via PD098095 inhibited the alteration of ADAMTS-5 and
      TIMP-4 expression induced by OPG. OPG therefore regulated the proliferation of
      chondrocytes via MEK/ERK signaling, and directly affected chondrocytes by
      influencing the expression profile of ADAMTS-5 and TIMP-4.

PMID- 24126802
TI  - Au(144-x)Pd(x)(SR)60 nanomolecules.
AB  - Au144-xPdx(SR)60 alloy nanomolecules were synthesized and characterized by ESI
      mass spectrometry to atomic precision. The number of Pd atoms can be varied by
      changing the incoming metal ratio and plateaus at 7 Pd atoms. Based on the
      proposed 3-shell structure of Au144(SR)60, we hypothesize that the Pd atoms are
      selectively incorporated into the central Au12 icosahedral core. 

PMID- 24126803
TI  - A panel of four immunohistochemical markers (CK7, CK20, TTF-1, and p63) allows
      accurate diagnosis of primary and metastatic lung carcinoma on biopsy specimens.
AB  - Accurate classification of lung cancer, as well as the differentiation between
      primary and metastatic carcinoma to the lung, mostly performed on biopsy or fine
      needle aspiration specimens, is critical for decisions on therapy and for
      determining prognosis. The limited amount of biopsy material available for
      morphological assessment has stimulated attempts to improve diagnostic accuracy
      through the use of immunohistochemistry (IHC), but an optimal IHC diagnostic
      algorithm has not been firmly established. We evaluated, on a retrospective
      series of biopsy specimens, the performance of a four-antibody IHC panel for
      accurate subclassification of non-small cell lung carcinoma (NSCLC) and for
      identification of metastatic carcinoma. Tumor morphology was assessed and IHC for
      CK7, CK20, TTF-1, and p63 was performed according to a two-step algorithm.
      Matched resection specimens served as gold standard and were compared with the
      corresponding biopsy. Of 443 biopsy specimens studied, 325 were diagnosed as
      primary carcinoma of the lung, 198 (44.7 %) as adenocarcinoma, 9 (2 %) as
      possibly adenosquamous carcinoma, 127 (28.7 %) as squamous cell carcinoma, and 40
      (9 %) as NSCLC not further classifiable. Ten cases (2.3 %) were classified as
      adenocarcinoma of unknown origin and 58 (13 %) as metastasis. Importantly, of the
      primary lung adenocarcinomas, 35 (17.7 %) had been considered on clinical grounds
      as a metastasis from a previously diagnosed primary tumor. Of the 55 cases
      submitted to surgical resection in 47 (85.5 %) the biopsy diagnosis was
      confirmed, revealing substantial agreement (kappa value = 0.757). Our two-step
      approach allows for accurate subclassification of NSCLC and also to distinguish
      between primary lung adenocarcinoma and metastasis, notably of colorectal
      adenocarcinoma, with crucial implications for appropriate patient management.

PMID- 24126804
TI  - Islet xenotransplantation from genetically engineered pigs.
AB  - PURPOSE OF REVIEW: Pigs have emerged as potential sources of islets for clinical
      transplantation. Wild-type porcine islets (adult and neonatal) transplanted into
      the portal vein have successfully reversed diabetes in nonhuman primates.
      However, there is a rapid loss of the transplanted islets on exposure to blood,
      known as the instant blood-mediated inflammatory reaction (IBMIR), as well as a T
      cell response that leads to rejection of the graft. RECENT FINDINGS: Genetically
      modified pig islets offer a number of potential advantages, particularly with
      regard to reducing the IBMIR-related graft loss and protecting the islets from
      the primate immune response. Emerging data indicate that transgenes specifically
      targeted to pig beta cells using an insulin promoter (in order to maximize target
      tissue expression while limiting host effects) can be achieved without
      significant effects on the pig's glucose metabolism. SUMMARY: Experience with the
      transplantation of islets from genetically engineered pigs into nonhuman primates
      is steadily increasing, and has involved the deletion of pig antigenic targets to
      reduce the primate humoral response, the expression of transgenes for human
      complement-regulatory and coagulation-regulatory proteins, and manipulations to
      reduce the effect of the T-cell response. There is increasing evidence of the
      advantages of using genetically engineered pigs as sources of islets for future
      clinical trials.

PMID- 24126805
TI  - Vascularized composite allotransplantation: towards tolerance and the importance
      of skin-specific immunobiology.
AB  - PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) is
      increasingly utilized in the restoration of complex injuries and tissue loss.
      Acute skin-targeted rejection episodes are common and concerns remain regarding
      the risks of conventional immunosuppression. We review current immunosuppressive
      regimens for VCA, progress with immunomodulatory and tolerance protocols, and
      highlight recent advances in cutaneous immunobiology which will have significant
      implications for future development in the field. RECENT FINDINGS: Advances in
      induction protocols have demonstrated effective prevention of early graft loss in
      hand transplantation, although long-term outcomes are still pending. Furthermore,
      recent findings in leukocyte populations within the skin and their mechanisms of
      communication reveal that considerable numbers of resident T-effector memory
      cells, including a T-regulatory subset, exist, and that epidermal Langerhans'
      cells communicate with these cells, mediating both immunity and tolerance to
      maintain skin homeostasis. SUMMARY: The majority of VCA centers utilize antibody
      mediated induction, followed by double or triple-agent maintenance
      immunosuppression. A clinical trial of a minimal-immunosuppression protocol based
      on bone marrow infusion reports encouraging interim results, but long-term follow
      up will be required. Skin remains the primary target of rejection in VCA. New
      data demonstrate extensive T-cell memory resident in skin, and complex
      interactions between these cells and epidermal Langerhans' cells will have
      implications for VCA rejection and tolerance, and warrant further investigation
      in the allogeneic setting.

PMID- 24126806
TI  - Successes and lessons learned after more than a decade of upper extremity and
      face transplantation.
AB  - PURPOSE OF REVIEW: This review aims to present the most recent updates on face
      and upper-extremity allotransplantation. RECENT FINDINGS: To date, 27 face and
      more than 89 upper-extremity allotransplantations have been performed. Both the
      face and hand transplants restored form, function and patients' social
      integration. The complications were comparable with solid organs; however, face
      transplantation, as well as the combination of face and double hand
      transplantation, presented with significant morbidity and mortality. Evidence of
      chronic rejection was confirmed in hand transplants, but it has not been reported
      yet for facial transplantation. Novel immunosuppressive protocols have allowed a
      decrease in the number and dosages of traditional immunosuppressants. With
      increased awareness that following face and hand transplantation, the return of
      function is more important than anatomical restoration of the missing parts,
      there has been an important shift in the ethical debate weighing the risks and
      benefits of face and hand allotransplantation. SUMMARY: Early results after face
      and upper extremity transplantation are promising, with 5-year survival rates
      greater than in solid organ transplants. However, these procedures still need to
      be closely monitored and the outcome data should be rigorously reported to the
      central patient registry database to allow continuous surveillance.

PMID- 24126807
TI  - Vascularized composite allografts and solid organ transplants: similarities and
      differences.
AB  - PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) is a
      treatment for complex tissue injuries and defects of extremities and face. During
      the past thirteen years, more than 100 VCA cases have been reported. Form and
      function restored with VCA have exceeded the results achieved with conventional
      surgical techniques. The review summarized the development in VCA over the past
      12 months with references of and comparison with solid organ transplantation.
      RECENT FINDINGS: The highlights reported in the latest publications included a
      better understanding of topical immunosuppressants for prevention and treatment
      of VCA rejection, mechanisms of chronic rejection and minimization of
      immunosuppressive maintenance treatment using a cell-based protocol in human
      upper-extremity transplantation. SUMMARY: We herein summarize the progress made
      in VCA in the last year with a focus on new clinical immunosuppressive strategies
      and novel targets for immunosuppression and immunomodulation including the
      application of mesenchymal stem cells for transplant tolerance.

PMID- 24126810
TI  - ABO blood groups and risk for progressive multifocal leukoencephalopathy.

PMID- 24126813
TI  - Dimensional dependence of phonon transport in freestanding atomic layer systems.
AB  - Due to the fast development of nanotechnology, we have the capability of
      manipulating atomic layer systems such as graphene, hexagonal boron nitride and
      dichalcogenides. The major concern in the 2-dimensional nanostructures is how to
      preserve their exceptional single-layer properties in 3-dimensional bulk
      structures. In this study, we report that the extreme phonon transport in
      graphene is highly affected by the graphitic layer stacking based on experimental
      investigation of the thermal conduction in few-layer graphene, 1-7 layers thick,
      suspended over holes of various diameters. We fabricate freestanding axisymmetric
      graphene structures without any perturbing substrate, and measure the in-plane
      transport property in terms of thermal conduction by using Raman spectroscopy.
      From the difference in susceptibility to substrate effect, size effect on hot
      spot temperature variation and layer number dependence of thermal conductivity,
      we show that the graphitic membranes with 2 or more layers have characteristics
      similar to 3-dimensional graphite, which are very different from those of 2
      dimensional graphene membranes. This implies that the scattering of out-of-plane
      phonons by interlayer atomic coupling could be a key mechanism governing the
      intrinsic thermal property. 

PMID- 24126814
TI  - Association of TNF-alpha -308 G > A and ACE I/D gene polymorphisms in
      hemodialysis patients with arteriovenous fistula thrombosis.
AB  - PURPOSE: Tumor necrosis factor-alpha (TNF - alpha) -308 G > A promoter
      polymorphism seems to be associated with adverse clinical outcome in hemodialysis
      patients (HD). Angiotensin-converting enzyme (ACE) gene may be the causative
      factor contributing to the deterioration of renal functions. The aim of this
      study was to investigate the relationship between vascular access failure and the
      genetic polymorphisms of ACE and TNF-alpha gene. METHODS: We enrolled and
      genotyped 47 HD patients with arteriovenous fistula (AVF) thrombosis, 51 HD
      patients without AVF thrombosis, and 40 healthy controls. The genotypes of these
      polymorphisms were determined by polymerase chain reaction and restriction
      fragment length polymorphism. RESULTS: The genotype distribution of TNF-alpha 
      308 G > A in patients with thrombosis was significantly different from the
      patients without thrombosis (p = 0.008). There was no significant difference
      between the two groups in terms of ACE I/D polymorphism (p = 0.213). CONCLUSION:
      Our results propose that TNF-alpha -308 G > A genotype may be a potential genetic
      marker on HD patients with AVF thrombosis.

PMID- 24126815
TI  - Patient satisfaction and its discontents.

PMID- 24126816
TI  - CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in
      human adipose tissue, both increasing after weight loss.
AB  - OBJECTIVE: FSP27 KO mice showed enhanced expression of mitochondrial genes,
      increased mitochondrial activity and smaller lipid droplets. Here, we aimed to
      investigate lipid droplet protein (CIDEC/FSP27 and perilipinA (PLIN1)) gene
      expression in human adipose tissue in association with obesity, insulin
      resistance and mitochondrial gene expression. DESIGN AND SUBJECTS: In cohort 1,
      CIDEC/FSP27, PLIN1, adipogenic (FASN, ACACA, PPARG, GLUT4) and mitochondrial
      (PPARGC1A, PPARGC1B, TFAM, MT-CO3) gene expression were analyzed in 171 adipose
      tissue samples (88 visceral adipose tissue (VAT) and 83 subcutaneous adipose
      tissue (SAT) depots) and in a time course experiment in human subcutaneous and
      visceral preadipocytes using real-time PCR. In cohort 2, the effects of bariatric
      surgery-induced weight loss were also evaluated in six caucasian morbidly obese
      women. Additionally, in cohort 2 FSP27 and PLIN1 protein levels were measured
      using western blotting. RESULTS: CIDEC/FSP27 (1.03+/-0.52 vs 0.49+/-0.23 relative
      gene expression unit (R.U.), P<0.0001) and PLIN1 (1.32+/-0.82 vs 0.63+/-0.42
      R.U., P<0.0001) gene were significantly more expressed in SAT than in VAT. In
      VAT, CIDEC/FSP27 and PLIN1 gene expression decreased with body mass index,
      percent fat mass, fasting glucose, fasting insulin, HOMA and were positively
      associated with adipogenic (PPARG, GLUT4, FASN and ACACA) and mitochondrial
      biogenesis (PPARGC1A, PPARGC1B, TFAM and MT-CO3)-related genes. Mitochondrial
      gene expression increased during adipocyte differentiation in parallel to FSP27
      and PLIN1 and other adipogenic genes. After bariatric surgery-induced weight
      loss, PLIN1 and CIDEC/FSP27 gene and protein expression in SAT increased
      significantly in parallel to adipogenic and mitochondrial genes. CONCLUSION:
      These findings suggest a positive functional interaction between CIDEC/FSP27,
      PLIN1 and mitochondrial biogenesis-related genes in human adipose tissue.

PMID- 24126817
TI  - Stem cell-based therapy for neonatal lung disease: it is in the juice.
AB  - Bronchopulmonary dysplasia, the chronic lung disease of prematurity, is the most
      common complication in extremely premature infants (born before 28 wk gestation).
      Despite advances in perinatal care, modern clinical management remains devoid of
      therapies specifically promoting lung repair and lung growth. Recent progress in
      stem cell biology has uncovered the promise of stem/progenitor cells to repair
      damaged organs. Contrary to the original theory that stem cells engraft and
      repopulate the damaged organ, evidence suggests that stem cells act via a
      paracrine mechanism. This review highlights the preclinical evidence for the
      therapeutic potential of cell-based therapies in animal models of neonatal
      chronic lung injury and the multiple therapeutic avenues offered by soluble stem
      cell-derived factors. 

PMID- 24126818
TI  - Chlorhexidine inhibits L1 cell adhesion molecule-mediated neurite outgrowth in
      vitro.
AB  - BACKGROUND: Chlorhexidine is a skin disinfectant that reduces skin and mucous
      membrane bacterial colonization and inhibits organism growth. Despite numerous
      studies assessing chlorhexidine safety in term infants, residual concerns have
      limited its use in hospitalized neonates, especially low-birth-weight preterm
      infants. The aim of this study was to assess the potential neurotoxicity of
      chlorhexidine on the developing central nervous system using a well-established
      in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion
      molecule (L1) as neurite outgrowth-promoting substrates. METHODS: Cerebellar
      granule neurons are plated on poly L-lysine, L1, or laminin. Chlorhexidine,
      hexachlorophene, or their excipients are added to the media. Neurons are grown
      for 24 h, fixed, and neurite length is measured. RESULTS: Chlorhexidine
      significantly reduced the length of neurites grown on L1 but not on laminin.
      Chlorhexidine concentrations as low as 125 ng/ml statistically significantly
      reduced neurite length on L1. Hexachlorophene did not affect neurite length.
      CONCLUSION: Chlorhexidine at concentrations detected in the blood following
      topical applications in preterm infants specifically inhibited L1-mediated
      neurite outgrowth of cerebellar granule neurons. It is now vital to determine
      whether the blood-brain barrier is permeable to chlorhexidine in preterm infants.

PMID- 24126819
TI  - Increased production of interleukin-10 in children with Down syndrome upon ex
      vivo stimulation with Streptococcus pneumoniae.
AB  - BACKGROUND: Children with Down syndrome (DS) have an increased susceptibility to
      infections, due to altered humoral and/or cellular immunity. The aim of the study
      was to determine the cytokine production in whole blood of children with DS upon
      stimulation with heat-killed Streptococcus pneumoniae and lipopolysaccharide
      (LPS), in comparison with their healthy siblings. METHODS: Whole blood of 61
      children with DS and 57 of their healthy siblings was stimulated with 200 ng/ml
      LPS and 4 * 10(7) colony-forming units/ml S. pneumoniae during 6, 24, and 48 h.
      Concentrations of pro- and anti-inflammatory cytokines, tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, and IL-10 were
      determined at all time points. RESULTS: Children with DS show an increased IL-10
      production upon stimulation with S. pneumoniae compared to their healthy
      siblings. At most time points, no significant differences were seen in cytokine
      production upon stimulation with LPS. CONCLUSION: Children with DS may be prone
      to a severe course of pneumococcal pneumonia, because of an increased anti
      inflammatory response.

PMID- 24126820
TI  - Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of
      hepatic arterial branches in biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is an infantile disorder characterized by
      progressive sclerosing cholangiopathy leading to biliary obstruction. First-line
      treatment of BA is hepatoportoenterostomy, the prognosis of which is related to
      age at surgery and to histological variables such as extent of fibrosis and
      ductular reaction. Hepatic arterial medial thickening (MT) suggests an
      arteriopathy in BA pathogenesis. We evaluated the expression of angiopoietin
      (ANGPT)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like
      domains 2 (TIE2) system in liver samples obtained from patients with BA,
      correlating it with MT, variables associated with disease severity, and
      postoperative prognosis. METHODS: ANGPT1, ANGPT2, and TIE2 expression levels were
      assessed by quantitative PCR in liver samples obtained from BA patients (n = 23)
      at portoenterostomy and age-matched infants with intrahepatic cholestasis (IHC; n
      = 7). Histological variables were morphometrically assessed. RESULTS: ANGPT1 and
      ANGPT2 were overexpressed in BA in comparison with IHC (P = 0.024 and P = 0.029,
      respectively). In BA, ANGPTs expression was positively correlated with MT
      (ANGPT1: rs = 0.59, P = 0.013; ANGPT2: rs = 0.52, P = 0.032), not with the
      variables associated with disease severity. TIE2 and ANGPTs expression levels
      were negatively correlated (ANGPT1: rs = -0.73, P < 0.001; ANGPT2: rs = -0.54, P
      = 0.007). CONCLUSION: In BA, there is overexpression of both ANGPT1 and ANGPT2,
      which is correlated with MT but not with age at portoenterostomy or with the
      histological variables associated with disease severity at the time of procedure.

PMID- 24126821
TI  - Mechanistic insight into the photocatalytic hydrogenation of 4-nitroaniline over
      band-gap-tunable CdS photocatalysts.
AB  - CdS photocatalysts with tunable band gaps (2.17-2.32 eV) were successfully
      prepared by a solvothermal method. Photocatalytic hydrogenation of 4-nitroaniline
      over the obtained samples was evaluated in the presence of HCO2NH4 as a hole
      scavenger upon purging with N2 under visible light irradiation (lambda >= 420
      nm). The CdS sample prepared by CdCl2 and sulfur powder in ethylenediamine showed
      excellent catalytic activity, giving 100% of 4-nitroaniline conversion and 95% of
      p-phenylenediamine selectivity after 35 min of visible light irradiation. The
      results of electron spin resonance revealed that its photoexcited holes could
      efficiently react with HCO2(-) ions within HCO2NH4 molecules to produce CO2(-)
      radicals with strong reductive abilities. Furthermore, photoexcited electrons of
      the obtained sample exhibited relatively strong reductive abilities as compared
      to other CdS samples. Therefore, this sample showed the highest catalytic
      activity among the CdS samples for the photocatalytic hydrogenation of 4
      nitroaniline. 

PMID- 24126822
TI  - Nano-structured ternary niobium titanium nitrides as durable non-carbon supports
      for oxygen reduction reaction.
AB  - A novel, highly stable, non-carbon support system for the oxygen reduction
      reaction (ORR) has been discovered in the form of nano-structured (NbxTi1-x)Ns (x
      = 0.25 and 0.5). Template-free, solid-solid separation synthetic approaches have
      been used for preparing these materials. The (NbxTi1-x)N materials have high
      specific surface area and better electronic conductivity than carbon-based
      supports. 

PMID- 24126823
TI  - Aberrant O-GlcNAc-modified proteins expressed in primary colorectal cancer.
AB  - O-GlcNAcylation is a post-translational modification of serine and threonine
      residues which is dynamically regulated by 2 enzymes; O-GlcNAc transferase (OGT)
      and O-GlcNAcase (OGA) that catalyze the addition and removal of a single N
      acetylglucosamine (GlcNAc) molecule, respectively. This modification is thought
      to be a nutrient sensor in highly proliferating cells via the hexosamine
      biosynthesis pathway, a minor branch of glycolysis. Although emerging evidence
      suggests that O-GlcNAc modification is associated with many types of cancer,
      identification of O-GlcNAc-modified proteins and their role in cancer remain
      unexplored. In the present study, we demonstrated that O-GlcNAcylation is
      increased in primary colorectal cancer tissues, and that this augmentation is
      associated with an increased expression of OGT levels. Using 2-dimensional O
      GlcNAc immunoblotting and LC-MS/MS analysis, 16 proteins were successfully
      identified and 8 proteins showed an increase in O-GlcNAcylation, including
      cytokeratin 18, heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1),
      hnRNP H, annexin A2, annexin A7, laminin-binding protein, alpha-tubulin and
      protein DJ-1. Among these identified proteins, annexin A2 was further confirmed
      to show overexpression of O-GlcNAc in all cancer samples. The results, therefore,
      indicate that aberrant O-GlcNAcylation of proteins is associated with colorectal
      cancer and that identification of O-GlcNAc-modified proteins may provide novel
      biomarkers of cancer.

PMID- 24126824
TI  - Biological properties of bone marrow-derived early and late endothelial
      progenitor cells in different culture media.
AB  - Ex vivo expansion of endothelial progenitor cells (EPCs) may be a promising
      strategy to overcome the clinical problem of limited cell numbers. As the culture
      medium is the key for the cell characteristics, the effects of different culture
      media on EPCs were investigated in the present study. Rat bone marrow mononuclear
      cells were cultured in different media, including M-199 media with 20% fetal
      bovine serum (FBS) and bovine pituitary extract (M1); M-199 media with 10% FBS,
      20 ng/ml vascular endothelial growth factor (VEGF) and 10 ng/ml basic fibroblast
      growth factor (bFGF; M2) or epidermal growth medium (EGM)-2MV media. The cell
      morphology and biological functions, such as proliferation, adhesion, migration,
      tube formation and nitric oxide (NO) production were subsequently assayed in
      vitro. Moreover, endothelial biomarkers and apoptosis were also analyzed. The
      results showed that endothelial-like cells appeared in all of the culture
      systems. First-passage cells, namely early EPCs, tended to form colonies in M2
      and EGM-2MV media but showed a fusiform shape in M1 media. The 3rd or 4th
      generation EPCs, namely late EPCs, cultured in EGM-2MV media exhibited increased
      adhesion, migration, tube formation and NO production as compared with EPCs in M1
      or M2 media. Furthermore, late EPCs cultured in EGM-2MV expressed higher levels
      of endothelial cell markers, such as von Willibrand factor (vWF)and CD31, but
      relatively greater levels of apoptosis were observed. In conclusion, cell culture
      conditions, for example the medium used, affects the biological properties of
      bone marrow-derived early and late EPCs.

PMID- 24126825
TI  - Molecular docking of thiamine reveals similarity in binding properties between
      the prion protein and other thiamine-binding proteins.
AB  - Prion-induced diseases are a global health concern. The lack of effective therapy
      and 100% mortality rates for such diseases have made the prion protein an
      important target for drug discovery. Previous NMR experimental work revealed that
      thiamine and its derivatives bind the prion protein in a pocket near the N
      terminal loop of helix 1, and conserved intermolecular interactions were noted
      between thiamine and other thiamine-binding proteins. Furthermore, water-mediated
      interactions were observed in all of the X-ray crystallographic structures of
      thiamine-binding proteins, but were not observed in the thiamine-prion NMR study.
      To better understand the potential role of water in thiamine-prion binding, a
      docking study was employed using structural X-ray solvent. Before energy
      minimization, docked thiamine assumed a "V" shape similar to some of the known
      thiamine-dependent proteins. Following minimization with NMR-derived restraints,
      the "F" conformation was observed. Our findings confirmed that water is involved
      in ligand stabilization and phosphate group interaction. The resulting refined
      structure of thiamine bound to the prion protein allowed the 4-aminopyrimidine
      ring of thiamine to pi-stack with Tyr150, and facilitated hydrogen bonding
      between Asp147 and the amino group of 4-aminopyrimidine. Investigation of the pi
      stacking interaction through mutation of the tyrosine residue further revealed
      its importance in ligand placement. The resulting refined structure is in good
      agreement with previous experimental restraints, and is consistent with the
      pharmacophore model of thiamine-binding proteins.

PMID- 24126826
TI  - Exploration of various electronic properties along the reaction coordinate for
      hydration of Pt(II) and Ru(II) complexes; the CCSD, MPx, and DFT computational
      study.
AB  - In the study behavior of molecular electrostatic potential, averaged local
      ionization energy, and reaction electronic flux along the reaction coordinate of
      hydration process of three representative Ru(II) and Pt(II) complexes were
      explored using both post-HF and DFT quantum chemical approximations. Previously
      determined reaction mechanisms were explored by more detailed insight into
      changes of electronic properties using omegaB97XD functional and MP2 method with
      6-311++G(2df,2pd) basis set and CCSD/6-31(+)G(d,p) approach. The dependences of
      all examined properties on reaction coordinate give more detailed understanding
      of the hydration process. 

PMID- 24126827
TI  - Coupling of mechanical and electronic properties of carbon nanotubes.
AB  - Because of the potential importance of carbon nanotubes (CNT) in renewable energy
      and other fields, molecular orbital ab initio calculations are used to study the
      relation between mechanical and electronic properties of such structures. We
      estimate a modulus of elasticity of 1.3 TPa and find out that the mechanism of
      CNT structure deformation is dependent on their chirality. Armchair and chiral
      nanotubes have ductile deformation fracture while zigzag have both ductile and
      brittle; on the other hand armchair nanotubes fracture and form two caps while
      chiral nanotubes adopt a helical-structure conformation. In addition, the energy
      gap between occupied and unoccupied molecular orbitals increases when nanotubes
      are under plastic deformation. This strong coupling between mechanical and
      electrical properties can be used to tune CNT mechanically to specific electronic
      bandgaps, affecting directly their electromagnetic absorption properties. 

PMID- 24126828
TI  - Pattern electroretinogram to detect glaucoma: comparing the PERGLA and the PERG
      Ratio protocols.
AB  - AIM: To detect early glaucoma, Porciatti and Ventura suggested in 2004 the
      pattern electroretinogram (PERG) protocol "PERGLA" with the following features:
      (1) skin electrodes, (2) steady-state reversal (15 rps) of horizontal 1.6 cpd
      gratings and (3) Fourier-based analysis. We compared this to our "PERG Ratio"
      protocol which uses (1) corneal (DTL) electrodes, (2) nearly the same reversal
      rate, but 2 check sizes of 0.8 degrees  and 16 degrees  and (3) Fourier-based
      analysis using the ratio of amplitudes to the 2 check sizes. METHODS: We examined
      16 eyes with glaucoma (age 64 +/- 7 years) and a control group (n = 13, age 59 +/
      8 years). Responses to all stimuli were simultaneously recorded with both
      electrode types using PERGLA-type gratings and checkerboards as necessary for the
      PERG Ratio. RESULTS: The median intra-individual test-retest coefficient of
      variation in normals pooled across stimuli for skin was 10.0 (95 % CI 1-85 %) and
      for DTL 9.95 (0.5-49 %), and they are thus nearly identical. The amplitudes
      obtained from skin were on average 30 % of those with DTL; the skin's signal-to
      noise ratio (SNR) was 66 % of DTL electrodes. Glaucoma detection was assessed via
      receiver operating characteristics (ROCs). Using skin electrodes, ROC area-under
      curve (AUC) was 72/76/72 % using gratings (PERGLA), checks or the PERG Ratio,
      respectively. Using DTL electrodes, the ROC areas were 60/67/77 %; the last value
      corresponds to the PERG Ratio protocol. CONCLUSIONS: Our results suggest that
      skin electrodes are a valid alternative to corneal electrodes: their advantages
      being no direct eye contact and smaller normal amplitude range compared to DTL;
      disadvantages: amplitude reduced to 30 % of DTL and SNR ratio reduced to 66 % of
      DTL. Efficacy in detecting glaucoma was a little higher with the PERG Ratio
      protocol (ROC AUC: 77 %, PERGLA: 72 %), but not significantly so.

PMID- 24126829
TI  - Magnet ingestions in children: a shared responsibility.

PMID- 24126830
TI  - Diagnostic and therapeutic utility of double-balloon enteroscopy in children.
AB  - OBJECTIVES: Diagnostic and therapeutic benefits of double-balloon enteroscopy
      (DBE) have been documented in adults, with few data available on pediatric
      patients. We evaluated the diagnostic and therapeutic utility of DBE in children.
      METHODS: A prospective assessment of 113 DBE procedures in 58 consecutive
      children younger than 18 years (36 boys, 22 girls; median age 12.7 years, range 1
      18 years) was performed for a variety of suspected small bowel (SB) disorders
      from January 2008 to August 2012 in a tertiary referral center for pediatric
      patients. All of the children had undergone upper gastrointestinal endoscopy and
      ileocolonoscopy. A total of 19 patients had undergone radiological investigations
      for SB (n = 11 magnetic resonance imaging; n = 5 barium enterography; n = 3
      computed tomography) and 54 patients had undergone wireless capsule endoscopy
      (WCE). RESULTS: The overall median (range) examination time was 92.5 (45-275)
      minutes. The median (range) estimated insertion length of SB distal to pylorus
      was 230 (80-450) cm and proximal to ileocecal valve was 80 (5-275) cm. The common
      indications for DBE were polyposis syndromes (n = 21) and obscure
      gastrointestinal bleeding (n = 16). The findings included polyps (n = 19),
      mucosal ulcers and erosions (n = 8), submucosal elevations with white nodules (n
      = 4), and angioma/angiodysplasia (n = 2). The overall diagnostic yield for SB
      lesions using DBE was 70.7% (41/58) and for WCE was 77.7% (42/54).
      Endotherapeutic intervention was successfully used in 46.5% (n = 27/58). The
      endoscopic, medical, and surgical contributions to change in management by DBE
      were 72.4% (n = 42/58). Three complications (5.2%) were noted with uneventful
      recovery. CONCLUSIONS: The diagnostic yield of DBE was comparable to WCE, but
      with the addition of therapeutic possibility and histological yield. We believe
      this technique could be a valuable addition to existing endoscopic techniques,
      complementary to WCE, and may be considered as an alternative diagnostic and
      therapeutic option in the SB in children.

PMID- 24126831
TI  - Toilet refusal syndrome in preschool children: do different subtypes exist?
AB  - OBJECTIVES: Toilet refusal syndrome (TRS) is a common, benign disorder in
      toddlers defined by the use of diapers and refusal of toilet for defaecation, but
      has not been described systematically in preschool children yet. The aim of the
      study was to analyse and identify possible subgroups of TRS. METHODS:
      Retrospective analysis of all of the consecutive children with TRS presented as
      outpatients in a clinic for elimination disorders. Patients had received a
      detailed paediatric and child psychiatric assessment, including the Child
      Behavior Checklist questionnaire. Three typical case vignettes are presented of
      TRS with constipation, oppositional defiant disorder, and sibling rivalry.
      RESULTS: Twenty-five children (10 boys) with a mean age of 5.2 (3.4-7.3) years
      were included-representing 2.5% of all of the children (n = 1001) presented. They
      had high rates of constipation (60%) and elimination disorders (24%-44%). Child
      psychiatric International Classification of Diseases-10th Edition disorders were
      common (40%) and heterogeneous, with significantly more boys affected, but no
      differences between children with and without constipation. CONCLUSIONS: This
      study shows that TRS occurs also in older preschool (and even school) children.
      At this later age, it is associated with constipation and behavioural disorders.
      The case vignettes show differences in therapy and may represent different
      subgroups of TRS. TRS is associated with constipation, elimination disorders, and
      psychiatric disorders. Owing to this variety of comorbid disorders, different
      therapeutic approaches are needed. A general screening for behavioural symptoms
      is recommended.

PMID- 24126832
TI  - Dual functions of Lactobacillus acidophilus NCFM as protection against rotavirus
      diarrhea.
AB  - OBJECTIVE: The aim of the study was to examine the dose effects of Lactobacillus
      acidophilus (LA) NCFM strain on rotavirus-specific antibody and B-cell responses
      in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV).
      METHODS: Pigs were inoculated with AttHRV vaccine in conjunction with high-dose
      LA (14 doses, total 2.2 * 10(6) colony-forming units [CFU]), intermediate-dose LA
      (MidLA) (9 doses, total 3.2 * 10(9) CFU), low-dose LA (LoLA) (5 doses, total 2.1
      * 10(6) CFU), or without LA feeding. Protection against rotavirus shedding and
      diarrhea was assessed upon challenge with a virulent HRV. Rotavirus-specific
      immunoglobulin A (IgA) and IgG antibodies in serum and rotavirus-specific IgA and
      IgG antibody-secreting cells (ASCs) and memory B cells in ileum, spleen, and
      blood of the pigs were measured and compared among treatment groups. RESULTS: The
      MidLA, but not high-dose LA or LoLA, significantly reduced rotavirus diarrhea
      (MidLA-only group) and significantly improved the protection conferred by AttHRV
      vaccine (MidLA + AttHRV group). Associated with the increased protection, MidLA
      significantly enhanced rotavirus-specific antibody, ASCs, and memory B-cell
      responses to AttHRV vaccine. High-dose LA or LoLA did not enhance virus-specific
      antibody and ASC responses, and hence did not improve the vaccine efficacy.
      CONCLUSIONS: These findings highlight the importance of dose selection and
      indicate that certain specific lactobacilli strains at the appropriate dose have
      the dual function of reducing rotavirus diarrhea and enhancing the immunogenicity
      and protective efficacy of rotavirus vaccines.

PMID- 24126833
TI  - Disease activity is an important factor for indeterminate interferon-gamma
      release assay results in children with inflammatory bowel disease.
AB  - BACKGROUND: Interferon-gamma release assay (IGRA) is widely used for screening of
      latent tuberculosis (TB) before and during biological therapy (BT). An
      indeterminate result of IGRA represents a limitation in the management of
      inflammatory bowel disease (IBD). Data on factors influencing IGRA results are
      scarce in children. The aim of the study was to identify factors influencing IGRA
      results in children with IBD. METHODS: Seventy-two children with IBD (59 Crohn
      disease, 11 ulcerative colitis, 2 IBD-unclassified) indicated for BT were tested
      for TB infection (history, TB skin test, chest radiograph, IGRA; QuantiFERON-TB
      Gold in tube [QFT]) and consecutively retested using QFT in 1-year intervals.
      RESULTS: We recorded 165 results of QFT (3% positive, 87% negative, and 10%
      indeterminate results). During follow-up we identified 4 conversions of negative
      QFT to positivity (3%) and 4 reversions (4%). Patients with indeterminate results
      of QFT had significantly lower actual weight-for-height z score (P = 0.022),
      higher platelet count (P = 0.00017), and lower levels of serum albumin (P =
      0.015) compared with patients with positive or negative QFT. Indeterminate QFT
      was associated with corticosteroid treatment, BT, and disease activity, but not
      with treatment by immunomodulators. In a subanalysis of patients with Crohn
      disease alone, Pediatric Crohn's Disease Activity Index was identified as single
      independent risk factor for indeterminate results (P = 0.00037). CONCLUSIONS:
      Although corticosteroid treatment is traditionally considered to be the main risk
      factor for indeterminate results of IGRA, the disease activity of IBD has even
      more profound effects on the results.

PMID- 24126834
TI  - Breast-feeding and weaning practices in the DONALD study: age and time trends.
AB  - OBJECTIVES: Besides influencing short- and long-term health status, infant
      feeding practices are known to have an effect on later food preferences. This
      study aimed to identify present trends in breast-feeding duration and weaning
      practices with special focus on preparation methods of complementary food (CF),
      that is, homemade and commercial CF. METHODS: In total, 1419 three-day weighed
      diet records collected between 2004 and 2012 from 366 children of the German
      DOrtmund Nutritional and Anthropometric Longitudinally Designed study ages 6 to
      24 months were analysed. Full (n = 339) and total breast-feeding duration (n =
      344) was collected by questionnaire. To investigate age and time trends, logistic
      regression and polynomial mixed regression models were used. RESULTS: Infants
      born between 2008 and 2012 were 3.3-fold less likely to be fully breast-fed for
      >=4 months than those born before 2004 (P < 0.0001). Overall, 59.3% commercial,
      21.1% homemade, and 19.6% combined CF was consumed by the study sample. Subjects
      with high commercial CF consumption (percentage of commercial CF > median 62%)
      were significantly older (P < 0.0001), showed shorter full and total breast
      feeding duration (P < 0.0001), and were more likely to have mothers with a lower
      educational status (P = 0.01). Both commercial and homemade CF showed opposing,
      nonlinear age trends. No time trends could be found. CONCLUSIONS: Decreasing
      duration of full breast-feeding should encourage health care providers to further
      promote longer breast-feeding duration. With the constantly high consumption of
      commercial CF at all ages, nutritional adequacy of both homemade and commercial
      CF needs to be investigated closer, as does their long-term influence on health
      and dietary habits, for example, fruit and vegetable intake.

PMID- 24126835
TI  - Receptor architecture of visual areas in the face and word-form recognition
      region of the posterior fusiform gyrus.
AB  - Recently, two extrastriate visual areas on the posterior fusiform gyrus, areas
      FG1 and FG2, were identified based on cytoarchitectonical criteria (Caspers et
      al. in Brain Struct Funct 218:511-526, 2013a). They are located within the object
      related ventral visual stream at the transition between early and higher-order
      (category-specific) visual areas. FG2 has a topographical position which is best
      comparable to the face or visual word-form recognition area. However, the precise
      function of FG2 is presently unknown. Since transmitter receptors are key
      molecules of neurotransmission, we analysed the regional and laminar distribution
      of 15 different receptor binding sites by means of quantitative in vitro receptor
      autoradiography. Significant differences between receptor densities of both areas
      were found for NMDA, GABAB, M3, nicotinic alpha4/beta2 and 5-HT1A receptors as
      well as for GABAA associated benzodiazepine binding sites. These results support
      the cytoarchitectonic segregation of FG1 and FG2 into two distinct cortical
      areas. In addition, principal component and hierarchical cluster analyses of the
      multireceptor data of both fusiform areas and 24 visual, auditory, somatosensory
      and multimodal association areas not only revealed the typical receptor
      architectonic characteristics of visual areas for FG1 and FG2, but also suggest
      their putative function as object recognition regions due to the similarity of
      their receptor fingerprints with those of areas of the ventral visual stream.
      Furthermore, FG1 and FG2 build a cluster with the multimodal association areas of
      the inferior parietal lobule. This underlines their hierarchically high position
      in the visual system of the human cerebral cortex.

PMID- 24126836
TI  - A novel functional imidazole fluorescent ionic liquid: simple and efficient
      fluorescent probes for superoxide anion radicals.
AB  - Novel imidazole fluorescent ionic liquids with anthracene groups (ImS-FILA) were
      synthesized for the first time to act as fluorescent probes. They were developed
      for the determination of superoxide anion radicals (O2 (*-)) in an aqueous
      system. O2 (*-) was produced by pyrogallol autoxidation. The fluorescence of ImS
      FILA was quenched by superoxide anion radicals. The pi-bond structure of the
      fluorescent molecules was oxidized and damaged. This method is very simple and
      sensitive. The linear range of sensitivity was 1-70 MUM ImS-FILA, and the
      detection limit for reactive oxygen species was 0.1 MUM. This method was used to
      detect superoxide radicals in papaya and garlic, with satisfactory results.
      Further work is needed to demonstrate the utility of this method in detecting
      reactive oxygen species in a biological aqueous system. 

PMID- 24126837
TI  - Probing high-affinity 11-mer DNA aptamer against Lup an 1 (beta-conglutin).
AB  - Aptamers are synthetic nucleic acids with great potential as analytical tools.
      However, the length of selected aptamers (typically 60-100 bases) can affect
      affinity, due to the presence of bases not required for interaction with the
      target, and therefore, the truncation of these selected sequences and
      identification of binding domains is a critical step to produce potent aptamers
      with higher affinities and specificities and lowered production costs. In this
      paper we report the truncation of an aptamer that specifically binds to beta
      conglutin (Lup an 1), an anaphylactic allergen. Through comparing the predicted
      secondary structures of the aptamers, a hairpin structure with a G-rich loop was
      determined to be the binding motif. The highest affinity was observed with a
      truncation resulting in an 11-mer sequence that had an apparent equilibrium
      dissociation constant (K D) of 1.7 * 10(-9) M. This 11-mer sequence was
      demonstrated to have high specificity for beta-conglutin and showed no cross
      reactivity to other lupin conglutins (alpha-, delta-, gamma-conglutins) and
      closely related proteins such as gliadin. Finally, the structure of the truncated
      11-mer aptamer was preliminarily elucidated, and the GQRS Mapper strongly
      predicted the presence of a G-quadruplex, which was subsequently corroborated
      using one-dimensional NMR, thus highlighting the stability of the truncated
      structure.

PMID- 24126838
TI  - Infrared spectroscopic study of stereo-controlled poly(N-isopropylacrylamide)
      with an extended chain conformation induced by adsorption on a gold surface.
AB  - Poly(N-isopropylacrylamide) (PNiPAM) compounds with various diad tacticities were
      prepared, and the molecular interaction properties in a thin film deposited on a
      gold surface were analyzed using infrared spectroscopy. The intramolecular and
      intermolecular interactions were found to depend on the tacticity, and only
      atactic (diad ratio 46 %) PNiPAM exhibits poor molecular interaction even in the
      bulk sample. On the other hand, the same series of compounds dissolved in an
      acetone solution were spread on a gold surface to form a thin film. In the
      dissolution process, the polymer molecules are relaxed via solvation, and they
      are bound to the gold surface by a molecular interaction to form a submonolayer
      thin film. In the thin film, the molecular interaction with the gold surface via
      the N-H group was monitored in the infrared spectra only for a nearly isotactic
      (m = 90) PNiPAM by an apparent shift of the N-H stretching vibration band. This
      shift was confirmed by changing the degree of hydrophilicity of the gold surface:
      a larger shift is found on a gold surface with stronger hydrophilicity. As a
      result, the conformation of a nearly isotactic molecule is found to be extended
      by the interaction with the gold surface, which works to immobilize the molecule.

PMID- 24126839
TI  - Analysis of free and bound phenolics in wine and grapes by GC-MS after automated
      SPE.
AB  - The results of validation of a method for the analysis of free and bound
      phenolics in wine and grapes are presented. Wine and grape extracts are
      fractionated by automated solid-phase extraction on Bond Elut PPL cartridges to
      give free and bound phenolic fractions. Bound fractions are subjected to acid
      hydrolysis, and the phenolics released are recovered by solid-phase extraction on
      Bond Elut PPL cartridges. The fractions are further purified by automated solid
      phase extraction on Bond Elut silica cartridges. After derivatisation to form
      trimethylsilyl ethers, the phenolics are determined by gas chromatography-mass
      spectrometry with selected ion monitoring. The method is suitable for robust,
      high-throughput monitoring of the concentrations of phenolics that can affect the
      palatability of wine. 

PMID- 24126840
TI  - Development and validation of a microfluidic chip-based nano-liquid
      chromatography-triple quadrupole tandem mass spectrometry method for a sensitive
      and reliable quantification of 7-ethyl-10-hydroxycamptothecin (SN38) in mouse
      plasma.
AB  - There is an increasing need for more sensitive analytical methods in
      pharmacokinetic studies, for example, for phase 0 clinical trials. A novel HPLC
      Chip-triple quadrupole mass spectrometer method (HPLC Chip-MS/MS method) for the
      quantification of 7-ethyl-10-hydroxycamptothecin (SN38) was developed, validated,
      and employed to the pharmacokinetic analysis of SN38 in ICR mice. Protein
      precipitation with a ratio of plasma/acetonitrile of 1:10 was chosen as the
      sample processing method. The nano-electrospray inserted in the microfluidic chip
      operated in positive mode, and selected reaction monitoring was used for
      quantification. Our bioanalytical method met all essential validation parameters
      selectivity, accuracy, precision, dilution integrity, calibration curve, matrix
      effect, recovery, and different stability tests (benchtop, freeze-thaw,
      autosampler stability). The calibration curves (weight 1/x (2)) were linear for
      the range 50-10,000 pg/mL. Clogging was not observed until the end of the
      lifetime of the microfluidic chip (350-400 injections), and carryover was
      practically eliminated through the introduction of a step gradient elution
      program. After intraperitoneal injection of 0.1 mg/kg irinotecan, SN38
      concentration could be measured up to 6 h with accuracy and precision. Thus, we
      developed a new, very sensitive HPLC Chip-MS/MS method for the determination of
      plasma SN38 that has been validated in compliance with guidelines from different
      regulation authorities.

PMID- 24126841
TI  - Thyroid metastases from squamous cell carcinoma of gallbladder.

PMID- 24126842
TI  - Cell proliferation and expression of connexins differ in melanotic and amelanotic
      canine oral melanomas.
AB  - Melanoma is a malignant neoplasm occurring in several animal species, and is the
      most frequently found tumor in the oral cavity in dogs. Melanomas are classified
      into two types: melanotic and amelanotic. Prior research suggests that human
      amelanotic melanomas are more aggressive than their melanotic counterparts. This
      study evaluates the behavior of canine melanotic and amelanotic oral cavity
      melanomas and quantifies cell proliferation and the expression of connexins.
      Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs
      during clinical procedures at the Veterinary Hospital of the School of Veterinary
      Medicine and Animal Science of the University of Sao Paulo, Brazil. After
      diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed
      the gross melanotic or amelanotic characteristics and tumors were classified
      according to the WHO. HMB45 or Melan A immunostainings were performed to confirm
      the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by
      counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26
      and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs
      bearing amelanotic melanomas presented a shorter lifespan in comparison to those
      with melanotic melanomas. Cell proliferation was significantly higher in
      amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly
      reduced in amelanotic melanomas. The results presented here suggest that oral
      cavity melanotic and amelanotic melanomas differ regarding their behavior, cell
      proliferation and connexin expression in dogs, indicating a higher aggressiveness
      of amelanotic variants.

PMID- 24126843
TI  - Bone morphogenetic protein signaling suppresses wound-induced skin repair by
      inhibiting keratinocyte proliferation and migration.
AB  - Bone morphogenetic protein (BMP) signaling plays a key role in the control of
      skin development and postnatal remodeling by regulating keratinocyte
      proliferation, differentiation, and apoptosis. To study the role of BMPs in wound
      induced epidermal repair, we used transgenic mice overexpressing the BMP
      downstream component Smad1 under the control of a K14 promoter as an in vivo
      model, as well as ex vivo and in vitro assays. K14-caSmad1 (transgenic mice
      overexpressing a constitutively active form of Smad1 under K14 promoter) mice
      exhibited retarded wound healing associated with significant inhibition of
      proliferation and increased apoptosis in healing wound epithelium. Furthermore,
      microarray and quantitative real-time reverse-transcriptase-PCR (qRT-PCR)
      analyses revealed decreased expression of a number of cytoskeletal/cell motility
      associated genes including wound-associated keratins (Krt16, Krt17) and Myosin VA
      (Myo5a), in the epidermis of K14-caSmad1 mice versus wild-type (WT) controls
      during wound healing. BMP treatment significantly inhibited keratinocyte
      migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded
      migration compared with WT controls. Finally, small interfering RNA (siRNA)
      mediated silencing of BMPR-1B in primary mouse keratinocytes accelerated cell
      migration and was associated with increased expression of Krt16, Krt17, and Myo5a
      compared with controls. Thus, this study demonstrates that BMPs inhibit
      keratinocyte proliferation, cytoskeletal organization, and migration in
      regenerating skin epithelium during wound healing, and raises a possibility for
      using BMP antagonists for the management of chronic wounds. 

PMID- 24126844
TI  - Fibronectin peptides that bind PDGF-BB enhance survival of cells and tissue under
      stress.
AB  - Stressors after injury from a multitude of factors can lead to cell death. We
      have identified four fibronectin (FN) peptides: two from the first FN type III
      repeat (FNIII1), one from the 13th FN type III repeat (FNIII13), and one from FN
      variable region (IIICS), which when tethered to a surface acted as platelet
      derived growth factor-BB (PDGF-BB) enhancers to promote cell survival. One of the
      FNIII1 peptides and its smallest (14-mer) bioactive form (P12) were also active
      in solution. Specifically, P12 bound PDGF-BB (KD=200 nM), enhanced adult human
      dermal fibroblast (AHDF) survival under serum starvation, oxidative or
      endoplasmic reticulum stressors, and limited burn-injury progression in a rat hot
      comb model. Furthermore, P12 inhibited endoplasmic reticulum stress-induced c-Jun
      N-terminal kinase (JNK) activation. Although many growth factors have been found
      to bind FN directly or indirectly, here we identify peptide sequences of growth
      factor-binding sites in FN. The finding of these peptides further delineated how
      the extracellular matrix protein FN can support cell survival. As the peptide P12
      is active in either soluble form or tethered to a substrate, it will have
      multifactorial uses as a bioactive peptide by itself or in tissue engineering.

PMID- 24126845
TI  - Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8
      mediated immune responses after skin scarification with vaccinia virus.
AB  - Skin scarification (s.s.) with vaccinia virus (VACV) is essential for generation
      of an optimal protective T-cell memory immune response. Dendritic cells (DCs),
      which are professional antigen-presenting cells, are required for naive T-cell
      priming and activation. At least three subsets of skin-resident DC have been
      identified: Langerhans cells (LCs), dermal Langerin+ DC (Lang+ dDC), and dermal
      Langerin- DC (Lang- dDC). Using Langerin-diphtheria toxin receptor mice and
      established mouse model of VACV delivered by s.s., we demonstrated that Lang+
      dDC, but not LC, are absolutely required for the induction of a rapid and robust
      antigen-specific CD8+ T-cell response after s.s. with VACV. The depletion of
      Lang+ dDC led to a significant delay in the priming and proliferation of antigen
      specific CD8+ T cells. Moreover, CD8+ T cells generated after VACV s.s. in the
      absence of Lang+ dDC lacked effector cytotoxic functions both in vitro and in
      vivo. While s.s.-immunized wild-type and LC-depleted mice controlled the
      progression of OVA257-264 expressing T-cell lymphoma EG7 (injected
      intradermally), the depletion of Lang+ dDC led to rapid lymphoma progression and
      mortality. These data indicate that of all skin DC subsets, Lang+ dDC is the most
      critical for the generation of robust CD8+ T-cell immunity after s.s. with VACV.

PMID- 24126846
TI  - OVO homolog-like 1, a target gene of the Wnt/beta-catenin pathway, controls hair
      follicle neogenesis.

PMID- 24126848
TI  - Delaying vaccination is not a safer choice.

PMID- 24126847
TI  - Potassium channel in the mitochondria of human keratinocytes.
AB  - The activation of mitochondrial potassium channels induces cytoprotection in
      various cell types. Hence, the identification of ion channels present in the
      inner mitochondrial membrane of keratinocytes is important in distinguishing
      possible protective mechanisms in these cells. In this paper, inner membrane
      mitochondrial ion channels of the human keratinocyte HaCaT cell line were
      investigated using a patch-clamp technique. We observed potassium-selective
      channel activity with a conductance of 83 pS at positive voltages. The I-V curve
      indicates that the observed channel has rectifying properties. Moreover, the
      channel activity was inhibited by acidic pH and 1 mM lidocaine. Using reverse
      transcriptase-PCR, we found an mRNA transcript for the TASK-3 (tandem pore domain
      acid-sensitive K channels) channel. We observed co-localization of the TASK-3
      protein and a mitochondrial marker in the mitochondria of HaCaT cells.
      Additionally, we showed that TASK-3 knockdown HaCaT cells markedly decreased
      viability after UVB radiation exposure compared with control cells. In summary,
      the single-channel activity and properties of a mitochondrial potassium channel
      in a keratinocyte HaCaT cell line have been described. 

PMID- 24126850
TI  - Relation between cervical and thoracic spinal canal stenosis and the development
      of spinal cord decompression sickness in recreational scuba divers.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVES: The intent of this
      study was to investigate the relationships between vertebral degenerative changes
      resulting in spinal canal stenosis, spinal cord lesions and the development of
      spinal cord decompression sickness (DCS) in scuba divers. SETTING: Referral
      hyperbaric facility, Toulon, France. METHODS: We examined 33 injured divers less
      than 50 years old by cervical and thoracic MRI and compared them with 34 matched
      control divers. The number of intervertebral disk abnormalities and the degree of
      canal compression were analyzed on T2-weighted sagittal images using a validated
      grading system developed recently. The presence and the distribution of
      hyperintense cord lesions in relation with the accident and the recovery status
      at 6 months were also assessed. RESULTS: Canal spinal narrowing was more common
      in injured divers than in controls (79% vs. 50%, OR=3.7 [95% CI, 1.3-10.8],
      P=0.021). We found a significant linear association between the extent of canal
      stenosis, multisegmental findings and the development of spinal cord
      decompression sickness. MRI intramedullary lesions were significantly more
      frequent in divers with incomplete recovery (OR=16 [95% CI, 2.6-99], P=0.0014),
      but statistical analysis failed to demonstrate a significant relationship between
      canal compression, signal cord abnormalities and a negative clinical outcome.
      CONCLUSIONS: These results suggest that divers with cervical and thoracic spinal
      canal stenosis, mainly due to disk degeneration, are at increased risk for the
      occurrence of spinal cord decompression sickness.

PMID- 24126851
TI  - Frequency and age effects of secondary health conditions in individuals with
      spinal cord injury: a scoping review.
AB  - STUDY DESIGN: Scoping review. OBJECTIVES: To gain a better understanding of the
      prevalence, course and association with age of secondary health conditions in
      individuals with spinal cord injury (SCI). SETTING: Seattle, Washington, USA.
      METHODS: We performed searches of electronic databases for studies published from
      1986-2011 that provided information regarding the prevalence, course or
      associations with age and duration of secondary health conditions in individuals
      with SCI. RESULTS: Ninety-two studies were included. The findings indicate that:
      (1) individuals with SCI experience a number of secondary health conditions, many
      of which occur at a higher rate in those with SCI than the normative population;
      (2) the most common conditions or symptoms are pain, bowel and bladder regulation
      problems, muscle spasms, fatigue, esophageal symptom and osteoporosis; (3) a
      number of conditions, including cardiovascular disease, diabetes, bone mineral
      density loss, fatigue and respiratory complications or infections, occur with
      higher frequency in older individuals or those with longer SCI duration, relative
      to younger individuals or those with shorter SCI duration; and (4) there is a
      marked lack of longitudinal research examining the natural course of health
      conditions in individuals aging with SCI. CONCLUSIONS: The findings support the
      conclusion that individuals with SCI show signs of 'premature aging' in different
      organ systems. Longitudinal research is needed to understand when problems are
      most likely to emerge, and to develop and test the efficacy of interventions to
      prevent these health conditions and their negative impact.

PMID- 24126852
TI  - A systematic review on bowel management and the success rate of the various
      treatment modalities in spina bifida patients.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To determine the different treatment
      modalities aimed at achieving fecal continence in spina bifida (SB) patients and
      their effectiveness. SETTING: International literature. METHOD: Electronic
      databases were searched ('Pubmed', 'Web of science', 'CINAHL' and 'Cochrane')
      identifying studies published since the mid-eighties and screened for relevance
      according to the Centre for Reviews and Dissemination procedure guidelines. A
      total of 37 studies were selected for inclusion. RESULTS: Studies on toilet
      sitting, biofeedback, anal plug, retrograde colon enemas (RCE) and antegrade
      colon enemas were found. Fecal continence was achieved in 67% of SB patients
      using conservative methods (n=509). In patients using RCE (n=190) an 80%
      continence rate was reached. Patients following surgical treatment (n=469)
      reached an 81% continence rate, however, 23% needed redo surgery because of
      complications. Better fecal continence was associated with an improved quality of
      life, which was negatively influenced by the amount of time spent on bowel
      management. CONCLUSION: Evidence favors an individually tailored stepwise
      approach with surgery as a final step in case of failure of conservative
      measures. Continued specialized support throughout life remains important to
      maintain continence. Cross-over and comparative trials are needed in order to
      optimize treatment.

PMID- 24126853
TI  - Ambulatory assistive devices and walking performance in patients with incomplete
      spinal cord injury.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: To primarily explore types of
      ambulatory assistive device (AAD) used and secondarily describe walking
      performance in independent ambulatory patients with spinal cord injury (SCI) who
      walked without and with various AADs as determined using walking speed and
      distance walked in 6 min. SETTING: A tertiary rehabilitation center and community
      hospitals, Thailand. METHODS: The data of 195 independent ambulatory patients
      with SCI were used to describe the use of an AAD. Among these, only 140 subjects
      were assessed for their walking speed and distance walked in 6 min. RESULTS: More
      than half of the subjects (64%) walked with an AAD in which most of them used a
      standard walker (45%), followed by a single-tip cane (11%) and bilateral crutches
      (8%), respectively. The walking speed and distance showed significant differences
      among the groups (P<0.001), except those who used walker versus crutches, and
      those who used crutches versus cane (P>0.05). Among the significant variables,
      types of AAD used had the greatest influence on walking speed and distance of the
      subjects. CONCLUSION: More than half of ambulatory subjects with SCI walked with
      an AAD in which most of them used a standard walker. However, the non-significant
      differences of walking performance between the groups may suggest the
      heterogeneity of walking ability in subjects who used the same type of AAD.
      Therefore, a method to facilitate the use of an AAD with less supportive ability
      would increase levels of independence for the patients.

PMID- 24126854
TI  - Hereditary spastic paraplegia is not associated with C9ORF72 repeat expansions in
      a Danish cohort.
AB  - OBJECTIVES: Hereditary spastic paraplegia (HSP) is a heterogeneous group of
      neurodegenerative disorders characterized by a progressive gait disorder, lower
      limb spasticity, hyper-reflexia, weakness and extensor plantar responses.
      Recently, large intronic hexanucleotide repeat expansions (GGGGCC) in C9ORF72
      have been found to cause frontotemporal dementia (FTD), amyotrophic lateral
      sclerosis and FTD with motor neuron disease. Owing to the overlapping phenotypes
      among HSP, amyotrophic lateral sclerosis and FTD with motor neuron disease along
      with shared pathological findings, we hypothesized that C9ORF72 expansions might
      be a genetic risk factor or modifier of HSP. METHODS: Clinically characterized
      HSP patients were investigated for elongations in the hexanucleotide repeat of
      C9ORF72. RESULTS: Upon analyses of the repeat lengths in the C9ORF72 gene in a
      Danish cohort of HSP patients, we found no expansions. CONCLUSION: We conclude
      that HSP is most likely not associated with repeat expansions in C9ORF72.

PMID- 24126855
TI  - Conversion chemotherapy followed by hepatic resection in colorectal cancer with
      initially unresectable liver-limited metastases.
AB  - The best management choice in colorectal cancer patients with unresectable liver
      only metastases should be represented by conversion chemotherapy aiming to reduce
      liver cancer deposits, thereby permitting curative surgery. Forty-eight
      consecutive stage IV colorectal cancer patients were treated with different
      chemotherapeutic regimens including biological drugs. Objective responses to
      chemotherapy were seen in 27 patients (56.2%; 95% CI 42.1-70.2%). Four patients
      (8.3%) showed complete response, 23 patients (47.9%) partial and 13 patients
      (27.1%) stable response. Eight patients (16.7%) progressed. The conversion rate
      was 35.4% (95% CI 21.8-48.9%) with 17 patients suitable for liver resection. Four
      complete responder patients refused surgery. The remaining 13 patients underwent
      curative hepatic resection (resection rate 27.1%; 95% CI 14.5-39.6%). The
      likelihood of a successful conversion chemotherapy appeared significantly related
      to the best response and to the K-Ras status. Wild-type K-Ras patients undergoing
      cetuximab therapy showed the best conversion rate. The four-year survival rate
      was significantly enhanced in converted compared to non-converted patients (57.1
      and 0%, respectively), and in resected compared to non-resected patients (53.3
      and 10.1%, respectively). Synchronous metastases and no conversion were shown to
      be the only covariates independently associated with a poorer long-term outcome.
      The possibility of curative liver surgery significantly prolongs outcome for
      colorectal cancer patients with unresectable liver-limited metastases.
      Prospective randomized trials are required to define the conversion rates with
      biological drugs.

PMID- 24126856
TI  - Advances in the genetics of eye diseases.
AB  - PURPOSE OF REVIEW: An update on heritable eye disease will allow informed patient
      counseling and improved patient care. RECENT FINDINGS: New loci and genes have
      been associated with identifiable heritable ocular traits. Molecular genetic
      analysis is available for many of these genes either as part of research or for
      clinical testing. The advent of gene array technologies has enabled screening of
      samples for known mutations in genes linked to various disorders. Exomic
      sequencing has proven to be particularly successful in research protocols in
      identifying the genetic causation of rare genetic traits by pooling patient
      resources and discovering new genes. Further, genetic analysis has led
      improvement in patient care and counselling, as exemplified by the continued
      advances in our treatment of retinoblastoma. SUMMARY: Patients and families are
      commonly eager to participate in either research or clinical testing to improve
      their understanding of the cause and heritability of an ocular condition. Many
      patients hope that testing will then lead to appropriate treatments or cures. The
      success of gene therapy in the RPE65 form of Leber congenital amaurosis has
      provided a brilliant example of this hope; that a similar trial may become
      available to other patients and families burdened by genetic disease.

PMID- 24126858
TI  - How to access and process FDA drug approval packages for use in research.

PMID- 24126857
TI  - beta-FeOOH nanorod bundles with highly enhanced round-trip efficiency and
      extremely low overpotential for lithium-air batteries.
AB  - beta-FeOOH nanorod (NR) catalysts prepared by ultrasonic-irradiated chemical
      synthesis enabled lithium-air cells to have high round-trip efficiency and
      extremely low overpotential as well as an outstanding rate capability. Good
      catalytic activities of the beta-FeOOH NR bundle could be ascribed to its crystal
      structure, which consists of 2 * 2 tunnels formed by edge- and corner-sharing
      Fe(O,OH)6 octahedra as well as to its one-dimensional morphology, which makes the
      configured electrode highly porous, indicating that the -OOH-based catalyst can
      be a good substitute for oxide-base catalysts in lithium-air batteries. The
      ultrasonic-irradiated chemical synthesis suggested here may be a good solution to
      optimize the morphology of catalyst materials for maximum catalytic activity. 

PMID- 24126859
TI  - A difficult case of atopic eczema.

PMID- 24126860
TI  - Nearly a third of children in India want to smoke when they grow up, study finds.

PMID- 24126861
TI  - Government takes lessons from medicine to embed evidence into policies.

PMID- 24126862
TI  - Checking GP patients' citizenship would be "bureaucratic nightmare," says GP
      leader.

PMID- 24126864
TI  - Incoherent dynamic light scattering by dilute dispersions of spherical particles:
      wavelength-dependent dynamics.
AB  - Dynamic light scattering (DLS) was performed on dilute suspensions of colloidal
      particles, where the scattering intensity was minimised by ellipsometric optics
      as in ellipsometric light scattering. Measurements at minimum intensity settings
      are dominated by the incoherent scattering properties, i.e. the deviations from
      the average scattering properties. The observed relaxation dynamics does not vary
      with the scattering angle, but depends on the wavelength lambda of the employed
      light. Therefore, the process has a lambda-dependence beyond the dependence
      included in the scattering vector. Such incoherent ellipsometric DLS could be
      applied to determine the residence time of particles in volumes with an extension
      comparable to lambda, and to obtain detailed information on the dynamics of
      complex systems which is usually hidden by the dominating diffusive process. 

PMID- 24126863
TI  - Interleukin-1beta upregulates matrix metalloproteinase-13 gene expression via c
      Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells.
AB  - Matrix metalloproteinase-13 (MMP-13) is crucial in the cleavage and remodeling of
      the extracellular matrix (ECM), and its expression levels are decreased following
      the induction of liver fibrosis. The aim of the present study was to investigate
      the role of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein
      kinase (MAPK) in interleukin (IL)-1beta-mediated MMP-13 gene expression in rat
      hepatic stellate cells (HSCs). In the present study, we demonstrated that IL
      1beta is capable of activating JNK and p38 in a time-dependent manner and the
      inhibition of the JNK pathway is able to increase MMP-13 mRNA expression;
      however, the inhibition of the p38 MAPK pathway is capable of inhibiting MMP-13
      gene expression. These data demonstrate that IL-1beta is able to promote MMP-13
      mRNA expression in rat HSCs and the JNK and p38 MAPK pathways were involved in
      this process. In summary, IL-1beta-induced MMP-13 mRNA expression is possibly
      mediated by cytoplasmic JNK and p38 MAPK pathways, and they play a distinct role
      in this process. Thus, the JNK and p38 MAPK pathway co-operatively mediate MMP-13
      mRNA expression in rat HSCs.

PMID- 24126865
TI  - Sex differences in co-occurring conditions of children with autism spectrum
      disorders.
AB  - This study investigated differences in co-occurring diagnoses made in females
      compared to males with autism spectrum disorders in 913 children (746 males and
      167 females) living in the United States with a current autism spectrum disorder
      diagnosis identified via caregiver-reported data from the National Survey of
      Children's Health 2007. The results indicated that overall, females had
      significantly fewer reported autism spectrum disorder co-occurring conditions
      than males. Females, compared to males, with a current autism spectrum disorder
      diagnosis had lower rates of past learning disorder, current mild learning
      disorder, and past anxiety diagnoses. Females with a current autism spectrum
      disorder diagnosis were more likely than males to have been diagnosed with a
      speech problem in the past, while males with a current autism spectrum disorder
      diagnosis were more likely than females to have a current diagnosis of a mild
      learning disability and a past diagnosis of learning disability. In addition,
      males with a current autism spectrum disorder diagnosis were more likely than
      females to have two or more co-occurring diagnoses. These findings provide
      insight into trends in sex differences in autism spectrum disorder co-occurring
      conditions. 

PMID- 24126866
TI  - The cost-effectiveness of supported employment for adults with autism in the
      United Kingdom.
AB  - Adults with autism face high rates of unemployment. Supported employment enables
      individuals with autism to secure and maintain a paid job in a regular work
      environment. The objective of this study was to assess the cost-effectiveness of
      supported employment compared with standard care (day services) for adults with
      autism in the United Kingdom. Thus, a decision-analytic economic model was
      developed, which used outcome data from the only trial that has evaluated
      supported employment for adults with autism in the United Kingdom. The main
      analysis considered intervention costs, while cost-savings associated with
      changes in accommodation status and National Health Service and personal social
      service resource use were examined in secondary analyses. Two outcome measures
      were used: the number of weeks in employment and the quality-adjusted life year.
      Supported employment resulted in better outcomes compared with standard care, at
      an extra cost of L18 per additional week in employment or L5600 per quality
      adjusted life year. In secondary analyses that incorporated potential cost
      savings, supported employment dominated standard care (i.e. it produced better
      outcomes at a lower total cost). The analysis suggests that supported employment
      schemes for adults with autism in the United Kingdom are cost-effective compared
      with standard care. Further research needs to confirm these findings. 

PMID- 24126867
TI  - Inversion effects in the perception of the moving human form: a comparison of
      adolescents with autism spectrum disorder and typically developing adolescents.
AB  - The "body inversion effect" refers to superior recognition of upright than
      inverted images of the human body and indicates typical configural processing.
      Previous research by Reed et al. using static images of the human body shows that
      people with autism fail to demonstrate this effect. Using a novel task in which
      adults, adolescents with autism, and typically developing adolescents judged
      whether walking stick figures-created from biological motion recordings and shown
      at seven orientations between 0 degrees  and 180 degrees -were normal or
      distorted, this study shows clear effects of stimulus inversion. Reaction times
      and "inverse efficiency" increased with orientation for normal but not distorted
      walkers, and sensitivity declined with rotation from upright for all groups.
      Notably, the effect of stimulus inversion was equally detrimental to both groups
      of adolescents suggesting intact configural processing of the body in motion in
      autism spectrum disorder. 

PMID- 24126868
TI  - The contribution of epigenetics to understanding genetic factors in autism.
AB  - Autism spectrum disorder is a grouping of neurodevelopmental disorders
      characterized by deficits in social communication and language, as well as by
      repetitive and stereotyped behaviors. While the environment is believed to play a
      role in the development of autism spectrum disorder, there is now strong evidence
      for a genetic link to autism. Despite such evidence, studies investigating a
      potential single-gene cause for autism, although insightful, have been highly
      inconclusive. A consideration of an epigenetic approach proves to be very
      promising in clarifying genetic factors involved in autism. The present article
      is intended to provide a review of key findings pertaining to epigenetics in
      autism in such a way that a broader audience of individuals who do not have a
      strong background in genetics may better understand this highly specific and
      scientific content. Epigenetics refers to non-permanent heritable changes that
      alter expression of genes without altering the DNA sequence itself and considers
      the role of environment in this modulation of gene expression. This review
      provides a brief description of epigenetic processes, highlights evidence in the
      literature of epigenetic dysregulation in autism, and makes use of noteworthy
      findings to illustrate how a consideration of epigenetic factors can deepen our
      understanding of the development of autism. Furthermore, this discussion will
      present a promising new way for moving forward in the investigation of genetic
      factors within autism. 

PMID- 24126869
TI  - Three-item Direct Observation Screen (TIDOS) for autism spectrum disorder.
AB  - We compared ratings on the Three-Item Direct Observation Screen test for autism
      spectrum disorders completed by pediatric residents with the Social Communication
      Questionnaire parent reports as an augmentative tool for improving autism
      spectrum disorder screening performance. We examined three groups of children (18
      60 months) comparable in age (18-24 month, 24-36 month, 36-60 preschool
      subgroups) and gender distribution: n = 86 with Diagnostic and Statistical Manual
      of Mental Disorders (4th ed., text rev.) autism spectrum disorders; n = 76 with
      developmental delay without autism spectrum disorders; and n = 97 with typical
      development. The Three-Item Direct Observation Screen test included the following
      (a) Joint Attention, (b) Eye Contact, and (c) Responsiveness to Name. The parent
      Social Communication Questionnaire ratings had a sensitivity of .73 and
      specificity of .70 for diagnosis of autism spectrum disorders. The Three-Item
      Direct Observation Screen test item Joint Attention had a sensitivity of .82 and
      specificity of .90, Eye Contact had a sensitivity of .89 and specificity of .91,
      and Responsiveness to Name had a sensitivity of .67 and specificity of .87. In
      the Three-Item Direct Observation Screen test, having at least one of the three
      items positive had a sensitivity of .95 and specificity of .85. Age, diagnosis of
      autism spectrum disorder, and developmental level were important factors
      affecting sensitivity and specificity. The results indicate that augmentation of
      autism spectrum disorder screening by observational items completed by trained
      pediatric-oriented professionals can be a highly effective tool in improving
      screening performance. If supported by future population studies, the results
      suggest that primary care practitioners will be able to be trained to use this
      direct procedure to augment screening for autism spectrum disorders in the
      community.

PMID- 24126870
TI  - Exploring the 'fractionation' of autism at the cognitive level.
AB  - Autism spectrum disorders are defined by difficulties across a range of areas:
      social and communication difficulties and restricted and repetitive behaviours
      and interests. It has been suggested that this triad of symptoms cannot be
      explained by a single cause at the genetic, neural or cognitive level. This
      article reviews the evidence for a 'fractionable' autism triad at the cognitive
      level, highlighting questions for future research. 

PMID- 24126871
TI  - Social conformity and autism spectrum disorder: a child-friendly take on a
      classic study.
AB  - Perhaps surprisingly, given the importance of conformity as a theoretical
      construct in social psychology and the profound implications autism has for
      social function, little research has been done on whether autism is associated
      with the propensity to conform to a social majority. This study is a modern,
      child-friendly implementation of the classic Asch conformity studies. The
      performance of 15 children with autism was compared to that of 15 typically
      developing children on a line judgement task. Children were matched for age,
      gender and numeracy and literacy ability. In each trial, the child had to say
      which of three lines a comparison line matched in length. On some trials,
      children were misled as to what most people thought the answer was. Children with
      autism were much less likely to conform in the misleading condition than
      typically developing children. This finding was replicated using a continuous
      measure of autism traits, the Autism Quotient questionnaire, which showed that
      autism traits negatively correlated with likelihood to conform in the typically
      developing group. This study demonstrates the resistance of children with autism
      to social pressure. 

PMID- 24126873
TI  - Developing a Nursing Personnel Policy to Address Body Art Using an Evidence-Based
      Model.

PMID- 24126872
TI  - Correction.

PMID- 24126874
TI  - Cancer cachexia: getting to the heart of the matter.

PMID- 24126875
TI  - Comparison of pathology of chronic total occlusion with and without coronary
      artery bypass graft.
AB  - AIMS: The aim of our study was to investigate chronic total occlusion (CTO) in
      human coronary arteries to clarify the difference between CTO with prior coronary
      artery bypass graft (CABG) and those without prior CABG. METHODS AND RESULTS: A
      total of 95 CTO lesions from 82 patients (61.6 +/- 14.0 years, male 87.8%) were
      divided into the following three groups: CTO with CABG (n = 34) (CTO+CABG), CTO
      without CABG--of long-duration (n = 49) (LD-CTO) and short-duration (n = 12) (SD
      CTO). A histopathological comparison of the plaque characteristics of CTO,
      proximal and distal lumen morphology, and negative remodelling between groups was
      performed. A total of 1127 sections were evaluated. Differences in plaque
      characteristics were observed between groups as follows: necrotic core area was
      highest in SD-CTO (18.6%) (LD-CTO: 7.8%; CTO+CABG: 4.5%; P = 0.02); calcified
      area was greatest in CTO+CABG (29.2%) (LD-CTO: 16.8%; SD-CTO: 12.1%; P = 0.009);
      and negative remodelling was least in SD-CTO [remodelling index (RI) 0.86]
      [CTO+CABG (RI): 0.72 and LD-CTO (RI): 0.68; P < 0.001]. Approximately 50% of
      proximal lumens showed characteristics of abrupt closure, whereas the majority of
      distal lumen patterns were tapered (79%) (P < 0.0001). CONCLUSION: These
      pathological differences in calcification, negative remodelling, and presence of
      necrotic core along with proximal and distal tapering, which has been associated
      with greater success, help explain the differences in success rates of
      percutaneous coronary intervention in CTO patients with and without CABG.

PMID- 24126876
TI  - A novel clinical risk prediction model for sudden cardiac death in hypertrophic
      cardiomyopathy (HCM risk-SCD).
AB  - AIMS: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac
      death (SCD) in young adults. Current risk algorithms provide only a crude
      estimate of risk and fail to account for the different effect size of individual
      risk factors. The aim of this study was to develop and validate a new SCD risk
      prediction model that provides individualized risk estimates. METHODS AND
      RESULTS: The prognostic model was derived from a retrospective, multi-centre
      longitudinal cohort study. The model was developed from the entire data set using
      the Cox proportional hazards model and internally validated using bootstrapping.
      The cohort consisted of 3675 consecutive patients from six centres. During a
      follow-up period of 24 313 patient-years (median 5.7 years), 198 patients (5%)
      died suddenly or had an appropriate implantable cardioverter defibrillator (ICD)
      shock. Of eight pre-specified predictors, age, maximal left ventricular wall
      thickness, left atrial diameter, left ventricular outflow tract gradient, family
      history of SCD, non-sustained ventricular tachycardia, and unexplained syncope
      were associated with SCD/appropriate ICD shock at the 15% significance level.
      These predictors were included in the final model to estimate individual
      probabilities of SCD at 5 years. The calibration slope was 0.91 (95% CI: 0.74,
      1.08), C-index was 0.70 (95% CI: 0.68, 0.72), and D-statistic was 1.07 (95% CI:
      0.81, 1.32). For every 16 ICDs implanted in patients with >=4% 5-year SCD risk,
      potentially 1 patient will be saved from SCD at 5 years. A second model with the
      data set split into independent development and validation cohorts had very
      similar estimates of coefficients and performance when externally validated.
      CONCLUSION: This is the first validated SCD risk prediction model for patients
      with HCM and provides accurate individualized estimates for the probability of
      SCD using readily collected clinical parameters.

PMID- 24126877
TI  - Immunity strikes: heart failure as a systemic disease.

PMID- 24126878
TI  - Higher levels of advanced glycation endproducts in human carotid atherosclerotic
      plaques are associated with a rupture-prone phenotype.
AB  - AIMS: Rupture-prone atherosclerotic plaques are characterized by inflammation and
      a large necrotic core. Inflammation is linked to high metabolic activity.
      Advanced glycation endproducts (AGEs) and their major precursor methylglyoxal are
      formed during high metabolic activity and can have detrimental effects on
      cellular function and may induce cell death. Therefore, we investigated whether
      plaque AGEs are increased in human carotid rupture-prone plaques and are
      associated with plaque inflammation and necrotic core formation. METHODS AND
      RESULTS: The protein-bound major methylglyoxal-derived AGE 5-hydro-5
      methylimidazolone (MG-H1) and N(epsilon)-(carboxymethyl)lysine (CML) were
      measured in human carotid endarterectomy specimens (n = 75) with tandem mass
      spectrometry. MG-H1 and CML levels were associated with rupture-prone plaques,
      increased protein levels of the inflammatory mediators IL-8 and MCP-1 and with
      higher MMP-9 activity. Immunohistochemistry showed that AGEs accumulated
      predominantly in macrophages surrounding the necrotic core and co-localized with
      cleaved caspase-3. Intra-plaque comparison revealed that glyoxalase-1 (GLO-1),
      the major methylglyoxal-detoxifying enzyme, mRNA was decreased (-13%, P < 0.05)
      in ruptured compared with stable plaque segments. In line, in U937 monoctyes, we
      found reduced (GLO-1) activity (-38%, P < 0.05) and increased MGO (346%, P <
      0.05) production after stimulation with the inflammatory mediator TNF. Direct
      incubation with methylglyoxal increased apoptosis up to two-fold. CONCLUSION:
      This is the first study showing that AGEs are associated with human rupture-prone
      plaques. Furthermore, this study suggests a cascade linking inflammation, reduced
      GLO-1, methylglyoxal- and AGE-accumulation, and subsequent apoptosis. Thereby,
      AGEs may act as mediators of the progression of stable to rupture-prone plaques,
      opening a window towards novel treatments and biomarkers to treat cardiovascular
      diseases.

PMID- 24126879
TI  - Expression of concern. 'Guidelines: Pre-operative Cardiac Risk Assessment and
      Perioperative Cardiac Management in Non-Cardiac Surgery', [Eur Heart J (2009) 30
      (22), 2769-2812; doi:10.1093/eurheartj/ehp337].

PMID- 24126881
TI  - Pentaerythrityl tetranitrate (PETN): a better nitrate?

PMID- 24126880
TI  - Stress echo applications beyond coronary artery disease.
AB  - Stress echocardiography is an established method for the diagnosis and prognostic
      stratification of coronary artery disease. In the last few years, the tremendous
      technological and conceptual versatility of this technique has been increasingly
      applied in challenging diagnostic fields. Today, in the echocardiography
      laboratory we can detect not only ischaemia from coronary artery stenosis, but
      can also recognize abnormalities of the coronary microvessels, myocardium, heart
      valves, pulmonary circulation, alveolar-capillary barrier, and right ventricle.
      Therefore, we evaluate coronary arteries as well as coronary microvascular
      disease (associated with diabetes and hypertension), suspected or overt dilated
      cardiomyopathy, systolic and diastolic heart failure, hypertrophic
      cardiomyopathy, athletes' hearts, valvular heart disease, congenital heart
      disease, incipient or overt pulmonary hypertension, and heart transplant patients
      for early detection of chronic or acute rejection as well as potential donors for
      better selection of suitable donor hearts. From a stress echo era with a one-fits
      all approach (wall motion by 2D-echo in the patient with known or suspected
      coronary artery disease) now we have moved on to an omnivorous, next-generation
      laboratory employing a variety of technologies (from M-Mode to 2D and pulsed,
      continuous and colour Doppler, to lung ultrasound and real-time 3D echo, 2D
      speckle tracking and myocardial contrast echo) on patients covering the entire
      spectrum of severity (from elite athletes to patients with end-stage heart
      failure) and ages (from children with congenital heart disease to the elderly
      with low-flow, low-gradient aortic stenosis). For each patient, we can tailor a
      dedicated stress protocol with a specific method to address a particular
      diagnostic question. Provided that the acoustic window is acceptable and the
      necessary expertise available, stress echocardiography is useful and convenient
      in many situations, from valvular to congenital heart disease, and whenever there
      is a mismatch between symptoms during stress and findings at rest. Increasing
      societal concern regarding cost, environment and radiation risks of medical
      imaging will lead to a preferential application of ultrasound over competing
      techniques, due to its unsurpassed versatility, portability, absence of
      radiation, and low cost. 

PMID- 24126882
TI  - HIV and the heart: the impact of antiretroviral therapy: a global perspective.
AB  - From a global perspective, cardiovascular disease (CVD) in human immunodeficiency
      virus (HIV) may result from cardiac involvement upon presentation of
      opportunistic infections in the presence of advanced immunosuppression, be a
      consequence of HIV-induced immune activation or derive from antiretroviral
      therapy-associated dyslipidaemia and insulin resistance. Indeed, in developed
      countries with unlimited access to antiretroviral therapy CVD has become one of
      the major causes of death in HIV. Therefore, cardiovascular risk reduction and
      lifestyle modifications are essential and careful selection of the antiretroviral
      drugs according to underlying cardiovascular risk factors of great importance. In
      developing countries with delayed roll-out of antiretroviral therapy pericardial
      disease (often related to TB), HIV-associated cardiomyopathy, and HIV-associated
      pulmonary hypertension are the most common cardiac manifestations in HIV. In
      Africa, the epicentre of the HIV epidemic, dynamic socio-economic and lifestyle
      factors characteristic of epidemiological transition appear to have positioned
      the urban African community at the cross-roads between historically prevalent and
      'new' forms of CVD, such as coronary artery disease. In this context,
      cardiovascular risk assessment of HIV-infected patients will become a critical
      element of care in developing countries similar to the developed world, and
      access to antiretroviral therapy with little or no impact on lipid and glucose
      metabolism of importance to reduce CVD in HIV. 

PMID- 24126884
TI  - The use of elements as a substitute for biomass in toxicokinetic studies in small
      organisms.
AB  - Determining pollutant concentrations in the tissues of experimental test
      organisms is necessary for understanding uptake and excretion mechanisms of
      toxicants. Using small organisms can make the determination of organism biomass
      inaccurate. We here propose the use of selected tissue element contents as a
      proxy for tissue biomass. Forty different elements were determined in tissues of
      the two worm species Enchytraeus crypticus and Caenorhabditis elegans derived
      from cultures exposed to combinations of varying temperatures and sublethal
      concentrations of Cu and Cd. Three criteria were used to select good biomass
      indicators: The element concentration must (1) be present in concentrations above
      the limit of quantification of the analytical method, (2) must be stable and (3)
      must not be affected by the treatment. If the organisms are believed to have
      significant amounts of soil in their gut, the element must also be present at
      higher concentrations in the tissue compared to the soil. The three elements K,
      Mg and P all lived up to the first three criteria for both worm species, showing
      correlation coefficients between element content and tissue biomass of 0.97, 0.96
      and 0.97 (n = 25) and 0.997, 0.998 and 0.992 (n = 10) for K, Mg and P in the E.
      crypticus and C. elegans, respectively. Only P would be an appropriate biomass
      indicator for organisms with a soil gut uptake assuming the tissue concentrations
      in soil eating organisms are similar to those measured in the present study.
      Using Mg as a biomass indicator on a verification dataset of Cu and Cd uptake in
      E. crypticus, compared to giving Cu and Cd content per individual organism,
      decreased the coefficient of variation from 31 +/- 21 to 21 +/- 17 % and from 34
      +/- 22 to 9.3 +/- 6.4 % for tissue Cu and Cd, respectively. We therefore conclude
      that the use of an element as a biomass indicator can reduce tissue concentration
      variability.

PMID- 24126883
TI  - Oxidative stress as a mechanism for toxicity of 2,4-dichlorophenoxyacetic acid
      (2,4-D): studies with goldfish gills.
AB  - The effects of exposure to the widely used herbicide, 2,4-dichlorophenoxyacetic
      acid (2,4-D), at environmentally permitted (1 mg L(-1)), slightly toxic (10 mg L(
      1)), and highly toxic (100 mg L(-1)) concentrations were analyzed in gills of
      goldfish, Carassius auratus, a popular fish model for ecotoxicological research.
      Fish were exposed to the pesticide in water for 96 h and an additional group of
      fish were treated by the highest 2,4-D concentration and then allowed to recover
      for further 96 h. Among markers of oxidative stress, goldfish exposure to 2,4-D
      did not affect carbonyl protein levels in the gills, but fish exposure to 100 mg
      L(-1) of 2,4-D enhanced lipid peroxide concentrations (by 58 %) and oxidized
      glutathione levels (by 49 %), the latter also significantly increasing (by 33 %)
      oxidized/total glutathione ratio. Activities of three enzymes of antioxidant
      defence also increased under 2,4-D exposure: superoxide dismutase (by 29-35 %),
      catalase (by 41 %), and glutathione peroxidase (by 19-33 %). Activities of other
      antioxidant associated enzymes as well as other potential markers of stress (e.g.
      aminotransferase enzymes, acetylcholinesterase, lactate metabolism) showed little
      or no response in gills to 2,4-D exposure. However, virtually all affected
      parameters returned to control values during recovery period. A combination of
      selected indices of oxidative stress and antioxidant defence, measured in fish
      gills, may provide to be effective biomarkers to assess environmental hazards of
      2,4-D to freshwater ecosystems.

PMID- 24126886
TI  - Surgical morbidity and mortality in obturator hernia: a 10-year retrospective
      risk factor evaluation.
AB  - Obturator hernia is a rare condition occurring predominantly in elderly, thin,
      female patients and causes significant morbidity and mortality. Due to obscure
      presenting symptoms and signs, diagnosis and management are often delayed. While
      previous studies have attributed the high mortality to the delay in diagnosis,
      current literature remains controversial about this issue. The aim of this study
      was to identify peri-operative risk factors associated with mortality in patients
      with obturator hernia at our hospital. METHODS: We retrospectively reviewed our
      series of 20 consecutive patients who underwent surgical repair of 21 obturator
      herniae and examined their clinical characteristics and post-operative outcomes.
      RESULTS: Overall mortality rate was 47.6 %. Survivors did not differ from non
      survivors in terms of basic demographics and operative parameters (operative
      time, blood loss and the need for intestinal resection). The use of computed
      tomography for pre-operative diagnosis was associated with reduced need for bowel
      resection, but did not result in shorter time to operation or improved morbidity
      and mortality. Our series demonstrated that early timing of surgery alone did not
      improve operative outcome. The absence of bowel motion and a high serum urea
      level at the time of operation were independent factors for mortality.
      CONCLUSIONS: Obturator hernia remains a highly lethal surgical emergency.
      Adequate peri-operative resuscitation may be the key to further improvement in
      surgical outcomes.

PMID- 24126885
TI  - Bone marrow-derived mesenchymal stem cells protect against cisplatin-induced
      acute kidney injury in rats by inhibiting cell apoptosis.
AB  - Acute kidney injury (AKI) is a common syndrome with a high mortality and
      morbidity rate. Recent developments in stem cell research have shown great
      promise for the treatment of AKI. The aim of this study was to investigate the
      therapeutic potential and anti-apoptotic mechanisms of action of bone marrow
      derived mesenchymal stem cells (BM-MSCs) in the treatment of AKI induced by
      cisplatin in vivo and in vitro. In vivo, adult male Sprague-Dawley rats (n=24)
      were administered BM-MSCs intravenously one day after cisplatin injection. The
      rats were sacrificed four days after the cisplatin injection and the effects of
      BM-MSCs on cisplatin-induced AKI, as well as the anti-apoptotic mechanisms
      involved were investigated. In vitro, NRK-52E cells, a rat renal proximal tubular
      cell line, were incubated in conditioned medium or complete medium in the
      presence or absence of cisplatin, followed by cell proliferation and apoptosis
      assays. The infusion of BM-MSCs preserved renal function, ameliorated renal
      tubular lesions, reduced apoptosis and accelerated tubular cell regeneration in
      the rats with cisplatin-induced AKI. The infusion of BM-MSCs also inhibited the
      activation of two mitogen-activated protein kinases, p38 and ERK, downregulated
      the expression of Bax and cleaved caspase-3, and upregulated the expression of
      Bcl-2. BM-MSC-conditioned medium improved NRK-52E cell viability and inhibited
      apoptosis. In conclusion, our results demonstrate that injecting rats with BM
      MSCs protects renal function and structure in cisplatin-induced AKI by inhibiting
      cell apoptosis in vivo. BM-MSC-conditioned medium protects renal cells from
      apoptosis induced by cisplatin in vitro. Hence, the infusion of BM-MSCs should be
      considered as a possible therapeutic strategy for the treatment of AKI. 

PMID- 24126887
TI  - Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces
      proliferation and promotes apoptosis in gastric cancer.
AB  - Our previous findings revealed that FGFR4 may be a novel therapeutic target for
      gastric cancer. The aim of the present study was to explore the effects of a
      combination of PD173074 (PD) and 5-fluorouracil (5-Fu) on the biological behavior
      of gastric cancer cell lines and the relevant mechanisms involved. MKN45, a
      gastric cancer cell line, was treated with each single agent alone or a
      combination of FGF19, PD and 5-Fu. Then, a series of functional assays were
      performed using CCK-8 assay and flow cytometry. Western blot analysis was used to
      determine the expression of signaling pathway and downstream-related molecules in
      the MKN45 cells following the different treatments. As the concentration of PD
      and 5-Fu increased, the cell viability gradually decreased; the viability of the
      combination group was less than the viability following single administration.
      Western blot analysis showed that FGFR4 expression was weak in the 5-Fu-treated
      groups when compared with the control. PD markedly increased the apoptosis rate
      of MKN45 cells when compared to the control; the apoptosis rate in the cells
      treated with the combination of PD and 5-Fu was higher than that in the cells
      following single treatment. Furthermore, PD reduced the expression of p-ERK and
      Bcl-xl and increased caspase-3 expression. Inhibition of the activity of FGFR4
      may be the main mechanisms of PD effect while 5-Fu reduced FGFR4 expression.
      Furthermore, the effects of the combination of 5-Fu and PD in inhibiting
      proliferation, increasing apoptosis and arresting cell cycle were superior to
      these effects following the single agent treatments, suggesting that the two
      drugs applied in combination may contribute to the effective treatment of gastric
      cancer. 

PMID- 24126888
TI  - Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse
      model of alcohol and high-fat diet-induced liver injury.
AB  - Endoplasmic reticulum (ER) stress is an important pathogenic mechanism for
      alcoholic (ALD) and nonalcoholic fatty liver disease (NAFLD). Iron overload is an
      important cofactor for liver injury in ALD and NAFLD, but its role in ER stress
      and associated stress signaling pathways is unclear. To investigate this, we
      developed a murine model of combined liver injury by co-feeding the mildly iron
      overloaded, the hemochromatosis gene-null (Hfe(-/)) mouse ad libitum with ethanol
      and a high-fat diet (HFD) for 8 weeks. This co-feeding led to profound
      steatohepatitis, significant fibrosis, and increased apoptosis in the Hfe(-/-)
      mice as compared with wild-type (WT) controls. Iron overload also led to
      induction of unfolded protein response (XBP1 splicing, activation of IRE-1alpha
      and PERK, as well as sequestration of GRP78) and ER stress (increased CHOP
      protein expression) following HFD and ethanol. This is associated with a muted
      autophagic response including reduced LC3-I expression and impaired conjugation
      to LC3-II, reduced beclin-1 protein, and failure of induction of autophagy
      related proteins (Atg) 3, 5, 7, and 12. As a result of the impaired autophagy,
      levels of the sequestosome protein p62 were most elevated in the Hfe(-/-) group
      co-fed ethanol and HFD. Iron overload reduces the activation of adenosine
      monophosphate protein kinase associated with ethanol and HFD feeding. We conclude
      that iron toxicity may modulate hepatic stress signaling pathways by impairing
      adaptive cellular compensatory mechanisms in alcohol- and obesity-induced liver
      injury.

PMID- 24126891
TI  - Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against
      ventilator-induced lung injury.
AB  - Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress
      injury and alveolar cell apoptosis, but the underlying mechanisms are poorly
      understood. We examined the effects of hypercapnic acidosis on the role of
      apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal
      kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high
      pressure ventilation stimulated rat lungs. Rats were ventilated with a peak
      inspiratory pressure (PIP) of 30 cmH2O for 4 h and randomly given FiCO2 to
      achieve normocapnia (PaCO2 at 35-45 mm Hg) or hypercapnia (PaCO2 at 80-100 mm
      Hg); normally ventilated rats with PIP of 15 cmH2O were used as controls. Lung
      injury was quantified by gas exchange, microvascular leaks, histology, levels of
      inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the
      ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar
      epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation.
      The results showed that injurious ventilation caused significant lung injury,
      including deteriorative oxygenation, changes of histology, and the release of
      inflammatory cytokines. In addition, the high-pressure mechanical stretch also
      induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated
      these responses, suppressing the ASK1 signal pathways with its downstream kinase
      phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia
      can attenuate cell apoptosis and oxidative stress damage in rat lungs during
      injurious ventilation, at least in part, due to the suppression of the ASK1
      JNK/p38 MAPK pathways.

PMID- 24126890
TI  - Low doses of celecoxib attenuate gut barrier failure during experimental
      peritonitis.
AB  - The intestinal barrier becomes compromised during systemic inflammation, leading
      to the entry of luminal bacteria into the host and gut origin sepsis.
      Pathogenesis and treatment of inflammatory gut barrier failure is an important
      problem in critical care. In this study, we examined the role of cyclooxygenase-2
      (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut
      barrier failure during experimental peritonitis in mice. I.p. injection of LPS or
      cecal ligation and puncture (CLP) increased the levels of COX-2 and its product
      prostaglandin E2 (PGE2) in the ileal mucosa, caused pathologic sloughing of the
      intestinal epithelium, increased passage of FITC-dextran and bacterial
      translocation across the barrier, and increased internalization of the tight
      junction (TJ)-associated proteins junction-associated molecule-A and zonula
      occludens-1. Luminal instillation of PGE2 in an isolated ileal loop increased
      transepithelial passage of FITC-dextran. Low doses (0.5-1 mg/kg), but not a
      higher dose (5 mg/kg) of the specific COX-2 inhibitor Celecoxib partially
      ameliorated the inflammatory gut barrier failure. These results demonstrate that
      high levels of COX-2-derived PGE2 seen in the mucosa during peritonitis
      contribute to gut barrier failure, presumably by compromising TJs. Low doses of
      specific COX-2 inhibitors may blunt this effect while preserving the homeostatic
      function of COX-2-derived prostanoids. Low doses of COX-2 inhibitors may find use
      as an adjunct barrier-protecting therapy in critically ill patients.

PMID- 24126889
TI  - Melanoma stem cells and metastasis: mimicking hematopoietic cell trafficking?
AB  - Malignant melanoma is a highly metastatic cancer that bears responsibility for
      the majority of skin cancer-related deaths. Amidst the research efforts to better
      understand melanoma progression, there has been increasing evidence that hints at
      a role for a subpopulation of virulent cancer cells, termed malignant melanoma
      stem or initiating cells (MMICs), in metastasis formation. MMICs are
      characterized by their preferential ability to initiate and propagate tumor
      growth and their selective capacity for self-renewal and differentiation into
      less tumorigenic melanoma cells. The frequency of MMICs has been shown to
      correlate with poor clinical prognosis in melanoma. In addition, MMICs are
      enriched among circulating tumor cells in the peripheral blood of cancer
      patients, suggesting that MMICs may be a critical factor in the metastatic
      cascade. Although these links exist between MMICs and metastatic disease, the
      mechanisms by which MMICs may advance metastatic progression are only beginning
      to be elucidated. Recent studies have shown that MMICs express molecules critical
      for hematopoietic cell maintenance and trafficking, providing a possible
      explanation for how circulating MMICs could drive melanoma dissemination. We
      therefore propose that MMICs might fuel melanoma metastasis by exploiting homing
      mechanisms commonly utilized by hematopoietic cells. Here we review the
      biological properties of MMICs and the existing literature on their metastatic
      potential. We will discuss possible mechanisms by which MMICs might initiate
      metastases in the context of established knowledge of cancer stem cells in other
      cancers and of hematopoietic homing molecules, with a particular focus on
      selectins, integrins, chemokines and chemokine receptors known to be expressed by
      melanoma cells. Biological understanding of how these molecules might be utilized
      by MMICs to propel the metastatic cascade could critically impact the development
      of more effective therapies for advanced disease. 

PMID- 24126892
TI  - Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment
      through its anti-inflammation and -apoptosis actions in aged mice.
AB  - Although the underlying mechanisms of isoflurane-induced cognitive impairments
      remain largely to be determined, neuronal inflammation and apoptosis are thought
      to be major contributors. Resveratrol is a naturally available herbal compound
      for the treatment of inflammatory and neurodegenerative diseases. We therefore
      aimed to investigate the effects of resveratrol on the isoflurane-induced
      cognitive impairments and the associated hippocampal inflammation responses and
      neuronal apoptosis in the aged mice. Fifteen-month-old male C57BL/6 mice received
      2 h of 1.5 % isoflurane or oxygen exposure 24 h after the intraperitoneal
      injection of resveratrol or saline daily for 7 consecutive days. Here, we showed
      that the isoflurane anesthesia decreased the freezing time to context
      significantly at 48 h after the isoflurane exposure in the fear conditioning
      test. The hippocampal levels of IL-1beta, TNF-alpha, NLRP3, cleaved caspase-3,
      and Bax increased significantly while the hippocampal levels of IkBalpha and Bcl
      2 decreased significantly at 6 and/or 48 h after the isoflurane anesthesia. All
      these effects induced by isoflurane were attenuated by resveratrol pretreatment.
      However, the isoflurane anesthesia had no significant effect on the hippocampal
      Sirt1. In conclusion, our results suggest that resveratrol attenuates the
      hippocampus-dependent cognitive impairment induced by isoflurane anesthesia
      through its anti-inflammation and anti-apoptosis effects in aged mice.

PMID- 24126894
TI  - High school physical educators' and sport coaches' knowledge of resistance
      training principles and methods.
AB  - The purpose of this study was to determine the level of knowledge that current
      and preservice high school (HS) physical educators and sport coaches possess
      regarding the principles and methods involved in youth resistance training (RT)
      and to determine if that knowledge was acceptable based on a predetermined
      criterion (passing score). A panel of 10 experts in RT or sport pedagogy used a
      Delphi technique to create a 90-question assessment (examination) that was
      administered to 287 HS physical educators and sport coaches and 140 university
      physical education teacher education (PETE) students. An analysis of the results
      revealed that neither group demonstrated the minimal knowledge necessary to
      design, implement, and supervise RT programs based on a passing score of 75%: HS
      physical educators/coaches, mean = 59.30, SD = 14.30, 95% confidence interval
      (CI) = 57.64-60.96], t(286) = -18.61, p = 0.000; university PETE students, mean =
      56.61, SD = 16.59, 95% CI = 53.84-59.38, t(139) = -13.12, p = 0.000. The pass
      rate for physical educators and sport coaches was 14.3% and for university PETE
      students it was 20.7%. The results of this study indicate that both current and
      preservice physical educators and sport coaches need additional education and
      training specific to the design and implementation of RT programs for HS
      students. Given that school districts typically require their educators attend in
      service training programs, it may be advisable to develop an in-service program
      that allows both current and preservice HS physical educators and sport coaches
      to earn an RT certification that specifically addresses the unique physical and
      psychosocial needs of school-aged youth.

PMID- 24126893
TI  - Mamestra configurata nucleopolyhedrovirus-A transcriptome from infected host
      midgut.
AB  - Infection of an insect by a baculovirus occurs in two distinct phases, an initial
      infection of host midgut by occlusion-derived virions (ODVs) and subsequent
      systemic infection of other tissues by budded virions (BV). A vast majority of
      investigations of the infection process have been restricted to cell culture
      studies using BV that emulate the systemic phase of infection. This is one of the
      first studies to investigate baculovirus gene expression in ODV infected midgut
      cells. We have focused on the critical first phase of in vivo infection by
      Mamestra configurata nucleopolyhedrovirus-A in M. configurata larvae, using qPCR
      and RNAseq mass sequencing to measure virus gene expression in midgut cells. The
      earliest genes detected by each method had significant overlap, including known
      early genes as well as genes unique to MacoNPV-A and genes of unknown function.
      The RNAseq data also revealed a large range of expression levels across all ORFs,
      which could not be measured using qPCR. This dataset provides a first whole
      genome transcriptomic analysis of viral genes required for virus infection in
      vivo and will provide the basis for functionally analyzing specific genes that
      may be critical elements in baculovirus midgut infectivity and host range.

PMID- 24126895
TI  - The effect of sodium bicarbonate ingestion on back squat and bench press exercise
      to failure.
AB  - This study examined the acute effects of NaHCO3 ingestion on repetitions to
      failure and rating of perceived exertion in the back squat and bench press in
      trained men. Eight resistance-trained men took part in this double-blind,
      randomized crossover experimental study whereby they ingested NaHCO3 (0.3 g.kg(
      1) body mass) or placebo (sodium chloride NaCl: 0.045 g.kg(-1) body mass)
      solution 60 minutes before completing a bout of resistance exercise (3 sets of
      bench press and back squat exercise to failure at an intensity of 80% 1
      repetition maximum). Experimental conditions were separated by at least 48 hours.
      Participants completed more repetitions to failure in the back squat after NaHCO3
      ingestion (p = 0.04) but not for bench press (p = 0.679). Mean +/- SD of total
      repetitions was 31.3 +/- 15.3 and 24.6 +/- 16.2 for back squat and 28.7 +/- 12.2
      and 26.7 +/- 10.2 for bench press in NaHCO3 and placebo conditions, respectively.
      Repetitions to failure decreased as set increased for the back squat and bench
      press (p = 0.001, both). Rating of perceived exertion significantly increased
      with set for the back squat and bench press (p = 0.002, both). There was no
      significant change in blood lactate across time or between conditions. There were
      however treatment * time interactions for blood pH (p = 0.014) and blood HCO3
      concentration (p = 0.001). After ingestion, blood pH and HCO3 (p = 0.008)
      concentrations were greater for the NaHCO3 condition compared with the placebo
      condition (p < 0.001). The results of this study suggest that sodium bicarbonate
      ingestion can enhance resistance exercise performance using a repetition to
      failure protocol in the first exercise in a resistance exercise session.

PMID- 24126896
TI  - The Influence of Load and Speed on Individuals' Movement Behavior.
AB  - Because individuals' movement patterns have been linked to their risk of future
      injury, movement evaluations have become a topic of interest. However, if
      individuals adapt their movement behavior in response to the demands of a task,
      the utility of evaluations comprising only low-demand activities could have
      limited application with regard to the prediction of future injury. This
      investigation examined the impact of load and speed on individuals' movement
      behavior. Fifty-two firefighters performed 5 low-demand (i.e., light load, low
      movement speed) whole-body tasks (i.e., lift, squat, lunge, push, and pull). Each
      task was then modified by increasing the speed, external load, or speed and load.
      Select measures of motion were used to characterize the performance of each task,
      and comparisons were made between conditions. The participants adapted their
      movement behavior in response to the external demands of a task (64 and 70% of
      all the variables were influenced [p <= 0.05] by changing the load and speed,
      respectively), but in a manner unique to the task and type of demand. The
      participants exhibited greater spine and frontal plane knee motion in response to
      an increase in speed when compared with increasing loads. However, there were a
      large number of movement strategies exhibited by individual firefighters that
      differed from the group's response. The data obtained here imply that individuals
      may not be physically prepared to perform safely or effectively when a task's
      demands are elevated simply because they exhibit the ability to perform a low
      demand activity with competence. Therefore, movement screens comprising only low
      demand activities may not adequately reflect an individual's capacity, or their
      risk of injury, and could adversely affect any recommendations that are made for
      training or job performance.

PMID- 24126897
TI  - Acute effects of an ascending intensity squat protocol on vertical jump
      performance.
AB  - The purpose of this study was to examine the acute effects of an ascending
      intensity squat protocol consisting of single-repetition exercises on subsequent
      vertical jump performance. Fourteen college weightlifters attended 2 testing
      sessions: squat (SQ) and control (CON) conditions. In the SQ condition, squat
      exercises with incremental loads (20% 1 repetition maximum [RM], 40% 1RM, 60%
      1RM, 80% 1RM, and maximal isometric [MI] half-squat exercise) were performed with
      a time interval of 3 minutes after submaximal cycling and static stretching.
      Maximum vertical jump height was measured at the beginning of the session and
      after cycling, static stretching, and each squat exercise in the SQ condition. In
      the CON condition, vertical jump height was measured at the same times with the
      subject resting on a chair after cycling and stretching. Vertical jump height
      gradually increased after 60% 1RM, 80% 1RM, and MI half-squat exercises compared
      with baseline values (i.e., first trial of vertical jump), whereas no change was
      observed in the CON condition. These results suggest that an ascending intensity
      squat protocol consisting of single-repetition exercises of sufficient intensity
      can be useful for athletes who require high muscular power.

PMID- 24126898
TI  - Validity and reliability of the Hawaii anaerobic run test.
AB  - This study examined the reliability and validity of the Hawaii anaerobic run test
      (HART) by comparing anaerobic capacity measures obtained to those during the
      Wingate Anaerobic Test (WAnT). Ninety-six healthy physically active volunteers
      (age, 22.0 +/- 2.8 years; height, 163.9 +/- 9.5 cm; body mass, 70.6 +/- 14.7 kg;
      body fat %, 19.29 +/- 5.39%) participated in this study. Each participant
      performed 2 anaerobic capacity tests: the WAnT and the HART by random assignment
      on separate days. The reliability of the HART was calculated from 2 separate
      trials of the test and then determined through intraclass correlation
      coefficients (ICCs). Blood samples were collected, and lactate was analyzed both
      pretest and posttest for each of the 2 exercise modes. Heart rate and rate of
      perceived exertion were also measured pre- and post-exercise. Hawaii anaerobic
      run test peak and mean momentum were calculated as body mass times highest or
      average split velocity, respectively. Intraclass correlation coefficients between
      trials of the HART for peak and mean momentum were 0.98 and 0.99, respectively
      (SEM = 18.8 and 25.7, respectively). Validity of the HART was established through
      comparison of momentum on the HART with power on the WAnT. High correlations were
      found between peak power and peak momentum (r = 0.88), as well as mean power and
      mean momentum (r = 0.94). The HART was considered to be a reliable test of
      anaerobic power. The HART was also determined to be a valid test of anaerobic
      power when compared with the WAnT. When testing healthy college-aged individuals,
      the HART offers an easy and inexpensive alternative maximal effort anaerobic
      power test to other established tests.

PMID- 24126899
TI  - The effect of ankle taping on the ground reaction force in vertical jump
      performance.
AB  - The purpose of this study was to investigate the effects of closed basket weave
      (CBW) ankle taping on the vertical ground reaction force during the contact phase
      before the take-off in vertical jump performance. We hypothesized that ankle
      taping would limit the capability for explosive force generation during the
      contact phase before the take-off in jump performance. Twelve healthy young men
      (age, 20.2 +/- 1.3 years; height, 1.76 +/- 0.05 m; body mass, 66.1 +/- 6.1 kg;
      mean +/- SD) performed a vertical jump performance on a force plate without (CON)
      or with ankle taping (CBW technique) of the right ankle joint. Vertical jump
      ability was assessed using 2 styles of vertical jump with no arm swing: a
      countermovement jump (CMJ) and squat jump (SJ). From the vertical ground reaction
      force (GRF), maximum jump height, vertical impulse (VI), rate of force
      development, maximum GRF (GRFmax), and time-series GRF (GRFts) during the contact
      phase before the take-off in jump performance were determined. Jump height was
      significantly lower for CBW (36.6 +/- 6.6 cm) than CON (38.1 +/- 6.7 cm) in CMJ,
      but not in SJ. Rate of force development and GRFts at 35, 40, 45, 50, 55, 60, and
      65% of total time of the contact phase in jumping performance were also
      significantly smaller for CBW than CON in CMJ, but not in SJ. Conversely, VI and
      GRFmax were not significantly different between the groups in either jump
      condition. These results suggest that ankle taping impairs CMJ performance,
      because of a decreased ability to develop large force rapidly on the ground
      before the take-off.

PMID- 24126900
TI  - Lower-body determinants of running economy in male and female distance runners.
AB  - A variety of training approaches have been shown to improve running economy in
      well-trained athletes. However, there is a paucity of data exploring lower-body
      determinants that may affect running economy and account for differences that may
      exist between genders. Sixty-three male and female distance runners were assessed
      in the laboratory for a range of metabolic, biomechanical, and neuromuscular
      measures potentially related to running economy (ml.kg(-1).min(-1)) at a range of
      running speeds. At all common test velocities, women were more economical than
      men (effect size [ES] = 0.40); however, when compared in terms of relative
      intensity, men had better running economy (ES = 2.41). Leg stiffness (r = -0.80)
      and moment arm length (r = 0.90) were large-extremely largely correlated with
      running economy and each other (r = -0.82). Correlations between running economy
      and kinetic measures (peak force, peak power, and time to peak force) for both
      genders were unclear. The relationship in stride rate (r = -0.27 to -0.31) was in
      the opposite direction to that of stride length (r = 0.32-0.49), and the
      relationship in contact time (r = -0.21 to -0.54) was opposite of that of flight
      time (r = 0.06-0.74). Although both leg stiffness and moment arm length are
      highly related to running economy, it seems that no single lower-body measure can
      completely explain differences in running economy between individuals or genders.
      Running economy is therefore likely determined from the sum of influences from
      multiple lower-body attributes.

PMID- 24126901
TI  - B cells: depletion or functional modulation in rheumatic diseases.
AB  - PURPOSE OF REVIEW: The availability of drugs directly and indirectly targeting
      the B cells has refocussed attention on the role of B lymphocytes in rheumatic
      autoimmune/inflammatory diseases (RAIDs), but their distinct therapeutic
      potential for certain diseases remains to be further assessed. RECENT FINDINGS:
      Although additional drugs are currently in clinical development targeting surface
      molecules (CD19, CD20, CD22, etc.) and cytokines (IL-6, IL-21, BAFF and APRIL)
      with key effects on B cell/plasma cell survival and differentiation,
      respectively, recent studies have also provided further insights into the effects
      of currently available drugs on protective immunity and mechanisms of the
      initiation and progression of RAIDs (i.e. rituximab, belimumab, mycophenolate and
      azathioprine). A key aspect of B-cell-directed drugs is their impact on
      continuous immune activation and chronic maintenance which may differ between
      individual RAIDs. SUMMARY: The translational advances in the area of B-cell
      depleting therapies and more sophisticated approaches to modulate key B-cell
      functions, such as blocking B-cell receptor downstream effects, interfering with
      the differentiation and survival of antigen-experienced memory B and plasma cells
      are of central interest. Differences in the efficacy and safety profiles of B
      cell depletion compared with B-cell-modulating therapies (including antigen
      specific tolerance induction) need to be further delineated.

PMID- 24126902
TI  - Emergence of sandflies (Phlebotominae) in Austria, a Central European country.
AB  - The possible existence of autochthonous sandfly populations in Central Europe
      north of the Alps has long been excluded. However, in the past years, sandflies
      have been documented in Germany, Belgium, and recently, also in Austria, close to
      the Slovenian border. Moreover, autochthonous human Leishmania and Phlebovirus
      infections have been reported in Central Europe, particularly in Germany. From
      2010 to 2012, sandfly trapping (740 trap nights) was performed at 53 different
      capture sites in Austria using battery-operated CDC miniature light traps. Sites
      were chosen on the basis of their climate profile in the federal states Styria,
      Burgenland, and Lower Austria. Sandfly specimens found were transferred to 70%
      ethanol for conservation. Identification was based on morphological characters of
      the male genitalia and the female spermathecae, respectively. Altogether, 24
      specimens, 22 females and 2 males, all identified as Phlebotomus
      (Transphlebotomus) mascittii Grassi, 1908, were found at six different sampling
      sites in all three federal states investigated. The highest number of catches was
      made on a farm in Lower Austria. Altogether, the period of sandfly activity in
      Austria was shown to be much longer than presumed, the earliest capture was made
      on July 3rd and the latest on August 28th. Sandflies have been autochthonous in
      Austria in small foci probably for long, but in the course of global warming,
      further spreading may be expected. Although P. mascittii is only an assumed
      vector of Leishmania spp.-data on its experimental transmission capacity are
      still lacking-the wide distribution of sandflies in Austria, a country thought to
      be free of sandflies, further supports a potential emergence of sandflies in
      Central Europe. This is of medical relevance, not only with respect to the
      transmission of Leishmania spp. for which a reservoir is given in dogs, but also
      with respect to the phleboviruses.

PMID- 24126903
TI  - Appropriateness of age thresholds for respiratory syncytial virus
      immunoprophylaxis in moderate-preterm infants: a cohort study.
AB  - IMPORTANCE Recommendations concerning the appropriate age threshold for
      respiratory syncytial virus (RSV) prophylaxis in moderate-preterm infants are
      highly debated. OBJECTIVE To determine the age at which moderate-preterm infants'
      risk of RSV hospitalization has decreased to the risk observed in low-risk term
      infants. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of Florida
      and Texas Medicaid fee-for-service billing records matched to birth certificates
      from Medicaid beneficiaries aged 0 to 12 months with a sibling younger than 5
      years and without other indications for RSV prophylaxis between January 1, 1999,
      and December 31, 2004. EXPOSURES For each state, we used discrete time survival
      analysis to develop age trend models for RSV hospitalizations for 2 groups:
      moderate-preterm infants (32-34 weeks' gestational age) and term infants (37-41
      weeks' gestational age). MAIN OUTCOMES AND MEASURES Age at which preterm infants'
      risk of RSV hospitalization equaled the risk for term infants at age 1 month.
      RESULTS Our cohort included 247,566 eligible infants with 5322 RSV
      hospitalizations. Preterm status doubled the risk for RSV hospitalization in both
      Florida (odds ratio = 2.41; 95% CI, 1.85-3.12) and Texas (odds ratio = 1.94; 95%
      CI, 1.64-2.30). Preterm infants' risk of RSV hospitalization was similar to that
      for 1-month-old term infants at ages 4.2 months (95% CI, 2.5-5.7) in Florida and
      4.5 months (95% CI, 2.8-6.4) in Texas. CONCLUSIONS AND RELEVANCE The age at which
      moderate-preterm infants showed RSV hospitalization risk similar to their healthy
      term counterparts supports the more restrictive age thresholds in RSV
      immunoprophylaxis recommendations. Further studies are warranted to investigate
      the age-dependent risk of RSV hospitalization in other RSV risk groups.

PMID- 24126904
TI  - Template electrosynthesis of tailored-made helical nanoswimmers.
AB  - We demonstrate a template electrosynthesis for large-scale low-cost preparation
      of remarkably small magnetically driven tailored-made helical nanoswimmers that
      display efficient propulsion behavior and hold considerable promise for future
      miniature devices in the human body. 

PMID- 24126905
TI  - Large animal model for retroperitoneal lymphatic and lung metastasis.
AB  - Retroperitoneal lymph node and lung metastasis are important prognostic factors
      for gynecologic cancer. The present study aimed to develop a new animal model for
      retroperitoneal lymph node and lung metastasis. VX2 squamous cell carcinoma tumor
      tissues were injected into the left gastrocnemius muscle of 38 healthy female New
      Zealand white rabbits. Animals were randomized into three groups according to day
      of sacrifice: 1, day 19; 2, day 22; and 3, day 25. Implanted primary tumor
      (IPTu), left and right retroperitoneal lymph node volumes and lung wet weights
      were measured on the day of sacrifice. The IPTu and left and right
      retroperitoneal lymph node volumes increased in a time-dependent manner. In
      addition, the proportion of animals with metastasis to the left peritoneal lymph
      nodes and the number of nodes involved increased over time. For days 19, 22 and
      25, the proportion of animals with nodal metastasis was 58.3, 84.6 and 100%,
      respectively, and the number of affected nodes (range) was 3 (2-3), 3 (3-5) and 4
      (4-5), respectively. No metastasis was detected in the right peritoneal lymph
      nodes. Metastasis to the lungs also increased with time, but was not
      statistically significant at days 19, 22 and 25 with metastasis present in 33.3,
      38.5 and 76.9% of animals, respectively. Rates of metastases to the left
      retroperitoneal lymph nodes and lungs were found to positively correlate with the
      volumes (r=0.416 and 0.449, respectively). The current study assessed the
      characterization of a rabbit VX2 carcinoma model. This animal model is likely to
      be useful for evaluating retroperitoneal lymph node and lung metastasis.

PMID- 24126906
TI  - Treatment of wastewater containing arsenic using Rhazya stricta as a new
      adsorbent.
AB  - The effective removal of heavy metals from aqueous wastes is among the most
      important issues for many industrialized countries. Removal of arsenic (As) from
      aqueous solutions was studied using Rhazia stricta biomass. The batch experiments
      are carried out to investigate the effect of the significant process parameters
      such as pH, contact time, solute concentration and adsorbent dose. The optimum pH
      required for maximum adsorption was found to be 5. The equilibrium data for the
      adsorption of As(V) on R. stricta are tested with various adsorption isotherm
      models such as Langmuir, Freundlich, Tempkin and Generalized equation. Results
      indicate the following order to fit the isotherm: Langmuir (1 and 2) > Tempkin >
      Generalized form > Freundlich. A comparison of two kinetic models showed that our
      data fitted well to the Elovich model.

PMID- 24126908
TI  - UV/H2O2 oxidation of arsenic and terbuthylazine in drinking water.
AB  - Arsenic is a widespread contaminant in the environment. The intake of water
      containing high concentrations of arsenic could have serious impact on human
      health, such as skin and lung cancer. In the European Union, thus, also in Italy,
      the arsenic limit in drinking water is 10 MUg L(-1). Several water remediation
      treatment technologies are available for arsenic removal. For some processes, the
      removal efficiencies can be improved after an oxidation step. Most full-scale
      applications are based on conventional oxidation processes for chemical
      micropollutant removal. However, if water contains arsenic and refractory organic
      contaminants, the advanced oxidation processes could be considered. The aim of
      this work was to investigate the effectiveness of ultraviolet (UV) radiation
      alone and in combination with hydrogen peroxide for the oxidation of arsenic and
      terbuthylazine (TBA). The experimental tests were performed in groundwater at the
      laboratory scale (0.1 mg L(-1) As(III) and 10 MUg L(-1) TBA). Hydrogen peroxide
      alone (15 mg L(-1)) was ineffective on both arsenic and TBA oxidation; the 253.7
      nm radiation alone did not oxidize arsenic(III), but photolyzed efficiently TBA
      (52 % removal yield at a UV dose of 1,200 mJ cm(-2)). The UV/H2O2 advanced
      oxidation (UV dose 600-2,000 mJ cm(-2), 5-15 mg L(-1) H2O2) was the most
      effective process for the oxidation of both arsenic and TBA, with observed
      oxidation efficiencies of 85 and 94 %, respectively, with 5 mg L(-1) H2O2 and a
      UV dose of 2,000 mJ cm(-2). 

PMID- 24126907
TI  - Organochlorine pesticide contamination in marine organisms of Yantai coast,
      northern Yellow Sea of China.
AB  - To evaluate the contamination of organochlorine pesticides (OCPs) in marine
      organisms and their potential health risk on consumers in the northern Yellow Sea
      of China, mollusks, wild shrimps, and crabs were collected from the Yantai coast,
      and the OCP contents in the samples were analyzed and compared. The results
      indicate that all the samples have been contaminated by OCPs, and OCP
      concentrations varied in individual species and in sampling sites. Among the
      studied OCPs, ?HCH and ?DDT concentrations ranged from 0.91 to 13.92 ng g(-1) and
      from 10.16 to 411.19 ng g(-1), respectively. Meretrix was highly enriched with
      HCHs, while the highest DDT concentration was found in Crassostrea. For the OCP
      isomers, beta-HCH was the predominant isomer of HCHs, and p,p'-DDE concentration
      was much higher than other isomers of DDTs. The concentrations of other OCPs
      (HCB, t-CHL, endrin, and mirex) were relatively low. For the shrimp and crab
      samples, Alpheus distinguendus samples accumulated a higher level of HCHs but
      lower DDTs than Oratosquilla aratoria and Carcinoplax vestitus in all sampling
      areas. HCHs in the samples of contrast area were not significantly lower than
      that of the sewage outfall area and port area, whereas DDTs in the samples of
      contrast area were relatively lower than that of the other two areas. Generally,
      all the OCP contents in the samples are in the range of the edible hygienic
      criteria except the total concentration of DDTs in Crassostrea. 

PMID- 24126909
TI  - Silencing HCCR2 expression inhibits the proliferation of leukemia cells by
      inducing apoptosis and promoting cell cycle arrest.
AB  - The human cervical cancer oncogene (HCCR2) has been found to be overexpressed in
      a variety of human malignant tumors cells, and its function is related to cell
      cycle progression and survival. However, the molecular mechanisms of action of
      HCCR2 in leukemia remain unclear. In this study, we used the RNA interference
      strategy to investigate the effects of HCCR2 knockdown in the K562 leukemia cell
      line, and to explore the potential mechanisms involved. Following transfection
      with small interfering RNA (siRNA) targeting HCCR2 (HCCR2-siRNA), we examined the
      effects of HCCR2 knockdown on cell morphology, cell proliferation, cell cycle
      progression and apoptosis in K562 cells. Morphological changes were evaluated by
      Wright-Giemsa staining. Cell cycle progression and apoptosis were measured by
      flow cytometry. The expression levels of genes related to the cell cycle and
      apoptosis were detected by quantitative RT-PCR (qRT-PCR) and western blot
      analysis. HCCR2 expression at the mRNA and protein level was significantly
      decreased following transfection with plasmids expressing HCCR2-siRNA. Silencing
      HCCR2 expression significantly suppressed cell proliferation, induced G1 cell
      cycle arrest and promoted the apoptosis of K562 cells. Additionally, we found
      that the expression of Bax, p53 and p21 was significantly increased, while Bcl-2
      expression was significantly decreased in the HCCR2-siRNA-transfected cells.
      However, the expression of p27 was not affected. These results suggest that the
      HCCR2 gene plays an important role in the tumorigenesis of leukemia, thus making
      it an attractive therapeutic target for acute leukemia. 

PMID- 24126910
TI  - Sporadic colon cancer murine models demonstrate the value of autoantibody
      detection for preclinical cancer diagnosis.
AB  - Although autoantibody detection has been proposed for diagnosis of colorectal
      cancer, little is known about their initial production and development
      correlation with cancer progression. Azoxymethane/dextran sodium sulfate
      (AOM/DSS)-treated mice developed colon adenocarcinoma in the distal colon similar
      to human sporadic colon cancer. We assessed this model together with AOM and DSS
      only models for their applicability to early detection of cancer. All AOM/DSS
      treated mice produced autoantibodies to tumor-associated antigens analogous to
      those observed in human colon cancer patients. Autoantibody response was related
      to tumor antigen overexpression. Cancer autoantibodies were detected 21 days
      after starting treatment, when no malignant histopathological features were
      detectable, and they increased according to tumor progression. When
      carcinogenesis was induced separately by AOM or DSS, only those mice that
      developed malignant lesions produced significant levels of autoantibodies. These
      findings demonstrate that autoantibody development is an early event in
      tumorigenesis and validates its use for preclinical colon cancer diagnosis. 

PMID- 24126911
TI  - Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1)
      expression through activation of protein kinase B and mitogen-activated protein
      kinase kinase pathways.
AB  - Mitogen-activated protein kinase phosphatase-1 (MKP-1), also known as dual
      specificity phosphatase-1 (DUSP-1), plays a crucial role in the deactivation of
      MAPKs. Several drugs with immune-suppressive properties modulate MKP-1 expression
      as part of their mechanism of action. We investigated the effect of mTOR
      inhibition through rapamycin and a dual mTOR inhibitor (AZD2014) on MKP-1
      expression. Low dose rapamycin led to a rapid activation of both AKT and ERK
      pathways with a subsequent increase in MKP-1 expression. Rapamycin treatment led
      to phosphorylation of CREB, transcription factor 1 (ATF1), and ATF2, three
      transcription factors that bind to the cyclic AMP-responsive elements on the Mkp
      1 promoter. Inhibition of either the MEK/ERK or the AKT pathway attenuated
      rapamycin-mediated MKP-1 induction. AZD2014 did not activate AKT but activated
      the ERK pathway, leading to a moderate MKP-1 induction. Using bone marrow-derived
      macrophages (BMDMs) derived from wild-type (WT) mice or mice deficient in AKT1
      and AKT2 isoforms or BMDM from targeted deficiency in MEK1 and MEK2, we show that
      rapamycin treatment led to an increased MKP1 expression in BMDM from WT but
      failed to do so in BMDMs lacking the AKT1 isoform or MEK1 and MEK2. Importantly,
      rapamycin pretreatment inhibited LPS-mediated p38 activation and decreased nitric
      oxide and IL-6 production. Our work provides a conceptual framework for the
      observed immune modulatory effect of mTOR inhibition. 

PMID- 24126912
TI  - WhiB7, an Fe-S-dependent transcription factor that activates species-specific
      repertoires of drug resistance determinants in actinobacteria.
AB  - WhiB-like (Wbl) proteins are well known for their diverse roles in
      actinobacterial morphogenesis, cell division, virulence, primary and secondary
      metabolism, and intrinsic antibiotic resistance. Gene disruption experiments
      showed that three different Actinobacteria (Mycobacterium smegmatis, Streptomyces
      lividans, and Rhodococcus jostii) each exhibited a different whiB7-dependent
      resistance profile. Heterologous expression of whiB7 genes showed these
      resistance profiles reflected the host's repertoire of endogenous whiB7-dependent
      genes. Transcriptional activation of two resistance genes in the whiB7 regulon,
      tap (a multidrug transporter) and erm(37) (a ribosomal methyltransferase),
      required interaction of WhiB7 with their promoters. Furthermore, heterologous
      expression of tap genes isolated from Mycobacterium species demonstrated that
      divergencies in drug specificity of homologous structural proteins contribute to
      the variation of WhiB7-dependent drug resistance. WhiB7 has a specific
      tryptophan/glycine-rich region and four conserved cysteine residues; it also has
      a peptide sequence (AT-hook) at its C terminus that binds AT-rich DNA sequence
      motifs upstream of the promoters it activates. Targeted mutagenesis showed that
      these motifs were required to provide antibiotic resistance in vivo.
      Anaerobically purified WhiB7 from S. lividans was dimeric and contained 2.1 +/-
      0.3 and 2.2 +/- 0.3 mol of iron and sulfur, respectively, per protomer
      (consistent with the presence of a 2Fe-2S cluster). However, the properties of
      the dimer's absorption spectrum were most consistent with the presence of an
      oxygen-labile 4Fe-4S cluster, suggesting 50% occupancy. These data provide the
      first insights into WhiB7 iron-sulfur clusters as they exist in vivo, a major
      unresolved issue in studies of Wbl proteins. 

PMID- 24126913
TI  - Proline scanning mutagenesis reveals a role for the flap endonuclease-1 helical
      cap in substrate unpairing.
AB  - The prototypical 5'-nuclease, flap endonuclease-1 (FEN1), catalyzes the essential
      removal of single-stranded flaps during DNA replication and repair. FEN1
      hydrolyzes a specific phosphodiester bond one nucleotide into double-stranded
      DNA. This specificity arises from double nucleotide unpairing that places the
      scissile phosphate diester on active site divalent metal ions. Also related to
      FEN1 specificity is the helical arch, through which 5'-flaps, but not continuous
      DNAs, can thread. The arch contains basic residues (Lys-93 and Arg-100 in human
      FEN1 (hFEN1)) that are conserved by all 5'-nucleases and a cap region only
      present in enzymes that process DNAs with 5' termini. Proline mutations (L97P,
      L111P, L130P) were introduced into the hFEN1 helical arch. Each mutation was
      severely detrimental to reaction. However, all proteins were at least as stable
      as wild-type (WT) hFEN1 and bound substrate with comparable affinity. Moreover,
      all mutants produced complexes with 5'-biotinylated substrate that, when captured
      with streptavidin, were resistant to challenge with competitor DNA. Removal of
      both conserved basic residues (K93A/R100A) was no more detrimental to reaction
      than the single mutation R100A, but much less severe than L97P. The ability of
      protein-Ca(2+) to rearrange 2-aminopurine-containing substrates was monitored by
      low energy CD. Although L97P and K93A/R100A retained the ability to unpair
      substrates, the cap mutants L111P and L130P did not. Taken together, these data
      challenge current assumptions related to 5'-nuclease family mechanism. Conserved
      basic amino acids are not required for double nucleotide unpairing and appear to
      act cooperatively, whereas the helical cap plays an unexpected role in hFEN1
      substrate rearrangement. 

PMID- 24126914
TI  - An intramolecular chaperone inserted in bacteriophage P22 coat protein mediates
      its chaperonin-independent folding.
AB  - The bacteriophage P22 coat protein has the common HK97-like fold but with a
      genetically inserted domain (I-domain). The role of the I-domain, positioned at
      the outermost surface of the capsid, is unknown. We hypothesize that the I-domain
      may act as an intramolecular chaperone because the coat protein folds
      independently, and many folding mutants are localized to the I-domain. The
      function of the I-domain was investigated by generating the coat protein core
      without its I-domain and the isolated I-domain. The core coat protein shows a
      pronounced folding defect. The isolated I-domain folds autonomously and has a
      high thermodynamic stability and fast folding kinetics in the presence of a
      peptidyl prolyl isomerase. Thus, the I-domain provides thermodynamic stability to
      the full-length coat protein so that it can fold reasonably efficiently while
      still allowing the HK97-like core to retain the flexibility required for
      conformational switching during procapsid assembly and maturation. 

PMID- 24126915
TI  - Structural basis of substrate conversion in a new aromatic peroxygenase:
      cytochrome P450 functionality with benefits.
AB  - Aromatic peroxygenases (APOs) represent a unique oxidoreductase sub-subclass of
      heme proteins with peroxygenase and peroxidase activity and were thus recently
      assigned a distinct EC classification (EC 1.11.2.1). They catalyze, inter alia,
      oxyfunctionalization reactions of aromatic and aliphatic hydrocarbons with
      remarkable regio- and stereoselectivities. When compared with cytochrome P450,
      APOs appear to be the choice enzymes for oxyfunctionalizations in organic
      synthesis due to their independence from a cellular environment and their greater
      chemical versatility. Here, the first two crystal structures of a heavily
      glycosylated fungal aromatic peroxygenase (AaeAPO) are described. They reveal
      different pH-dependent ligand binding modes. We model the fitting of various
      substrates in AaeAPO, illustrating the way the enzyme oxygenates polycyclic
      aromatic hydrocarbons. Spatial restrictions by a phenylalanine pentad in the
      active-site environment govern substrate specificity in AaeAPO. 

PMID- 24126919
TI  - Desire for social contact, not empathy, may explain "rescue" behavior in rats.
AB  - Ben-Ami Bartal et al. (Science 334:1427-1430, 2011) showed that a rat in an open
      space (free rat) would touch the front door of a restraining tube to open its
      rear door, thereby enabling a rat trapped within (trapped rat) to enter a larger
      space that was farther away from the free rat. Since opening the rear door
      distanced the trapped rat from the free rat, Ben-Ami Bartal et al. argued free
      rat behavior could not be motivated by the pursuit of social contact. Instead,
      this rat was empathically motivated, its goal being to reduce the presumed
      distress of the rat trapped in the restraining tube. In two experiments, we show
      that (a) a free rat will not learn to touch the front door to open the rear door
      when it is the first condition of the experiment; (b) over time, a trapped rat
      will often return to a restraining tube despite its presumed aversiveness; and
      (c) a free rat experienced in touching the front door will continue to touch it
      even if touching does not free the trapped rat. We explain these results and Ben
      Ami Bartal et al.'s in terms of two processes, neophobia and the pursuit of
      social contact. When first placed in a restraining tube, neophobia causes the
      trapped rat to escape the tube when the rear door is opened. Across sessions,
      neophobia diminishes, permitting the rats' pursuit of social contact to emerge
      and dominate free- and trapped-rat behavior.

PMID- 24126916
TI  - Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel organic anion
      transporting polypeptide.
AB  - The organic anion-transporting polypeptide (OATP/Oatp) superfamily includes a
      group of polyspecific transporters that mediate transport of large amphipathic,
      mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are
      involved in the disposition and elimination of numerous physiological and foreign
      compounds. However, in non-mammalian species, the functional properties of Oatps
      remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain
      insights into the functional and structural evolution of the OATP1/Oatp1
      superfamily. We show that diversification of the OATP1/Oatp1 family occurs after
      the emergence of jawed fish and that the OATP1A/Oatp1a and OATP1B/Oatp1b
      subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in
      teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to
      mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological
      role in transport and balance of steroid hormones. Oatp1d1 activity is dependent
      upon pH gradient, which could indicate bicarbonate exchange as a mode of
      transport. Our analysis of evolutionary conservation and structural properties
      revealed that (i) His-79 in intracellular loop 3 is conserved within OATP1/Oatp1
      family and is crucial for the transport activity; (ii) N-glycosylation impacts
      membrane targeting and is conserved within the OATP1/Oatp1 family with Asn-122,
      Asn-133, Asn-499, and Asn-512 residues involved; (iii) the evolutionarily
      conserved cholesterol recognition interaction amino acid consensus motif is
      important for membrane localization; and (iv) Oatp1d1 is present in dimeric and
      possibly oligomeric form in the cell membrane. In conclusion, we describe the
      first detailed characterization of a new Oatp transporter in zebrafish, offering
      important insights into the functional evolution of the OATP1/Oatp1 family and
      the physiological role of Oatp1d1. 

PMID- 24126920
TI  - Manipulation of walnuts to facilitate opening by the great spotted woodpecker
      (Picoides major): is it tool use?
AB  - True tool use has been documented in some bird species, but to our knowledge, it
      has not been shown in woodpeckers. Here, we investigated the ability of Picoides
      major to open nuts of Juglans mandshurica by consistently inserting walnuts
      between tree branches in a specific position that facilitated nut opening. As
      seen in these birds, we showed that woodpeckers removed 96% of the nuts of J.
      mandshurica from experimental seed trays and inserted each nut in a precise
      position that specifically allowed nut cracking. When we inserted nuts in an
      alternative position, woodpeckers manipulated and repositioned nuts to allow nut
      opening. In contrast, when we inserted the nuts in positions preferred for nut
      opening, woodpeckers did not alter their position and instead opened the nuts. We
      suggest that the origin of this behavior, as in other forms of tool use, likely
      requires a higher cognitive ability in these birds.

PMID- 24126921
TI  - An update on the importance of monitoring serum magnesium in advanced disease
      patients.
AB  - PURPOSE OF REVIEW: Patients with advanced diseases are exposed to many causes of
      hypomagnesaemia, the most frequent being pharmacological causes through the
      administration of chemotherapy, antibiotics, proton pump inhibitors, and so on.
      The objective of this review is to demonstrate the importance of measuring
      magnesium levels in the blood of these patients. RECENT FINDINGS: In the last
      decade, studies have been published showing a direct relationship between low
      levels of magnesium and nonspecific symptoms including pain that is difficult to
      control. Nevertheless, hypomagnesaemia is still being omitted as a differential
      diagnosis in many such patients. SUMMARY: A review of recently published studies
      regarding the clinical presentation of hypomagnesaemia in patients with advanced
      cancer and other chronic diseases is presented. Many of the clinical conditions
      are reportedly alleviated with intravenous or even oral magnesium administration.
      The presence of nonspecific neurological signs and risk factors for
      hypomagnesaemia could serve as an indication that serum magnesium should be
      determined in these patients.

PMID- 24126922
TI  - Mitigation of CO poisoning on functionalized Pt-TiN surfaces.
AB  - It has been previously reported that the system of single Pt atoms embedded in N
      vacancy (V(N)) sites on the TiN(100) surface (Pt-TiN) could be a promising
      catalyst for proton exchange membrane fuel cells (PEM FCs). The adsorption of
      molecules on Pt-TiN is an important step, when it is incorporated as the anode or
      cathode of PEM FCs. Utilizing first principles calculations based on density
      functional theory, systematic investigations are performed on the adsorption of
      several atomic and molecular species on the Pt-TiN system, as well as the co
      adsorption of them. The favorable binding sites and adsorption energies of
      several molecular species, namely carbon dioxide (CO2), carbon monoxide (CO),
      oxygen (O2), hydrogen (H2), hydroxyl (OH), an oxygen atom (O), and a hydrogen
      atom (H), are explored. For each, the adsorption energy and preferred binding
      site are identified and the vibrational frequencies calculated. It is found that
      CO2, CO and H prefer the Pt top site while OH and O favorably adsorb on the Ti
      top site. When CO and OH are co-adsorbed on the Pt-TiN(100) surface, OH weakens
      the adsorption of CO. The weakening effect is enhanced by increasing the coverage
      of OH. A similar behavior occurs for H and OH co-adsorption on the Pt-TiN(100)
      surface. Because co-adsorption with OH and H species weakens the adsorption of CO
      on Pt-TiN, it is expected that the acid and base conditions in PEM FCs could
      mitigate CO poisoning on functionalized Pt-TiN surfaces.

PMID- 24126923
TI  - Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with
      poor prognosis of patients with resected non-small cell lung cancer.
AB  - Specific and sensitive enough molecular biomarkers are lacking to accurately
      predict the survival of non-small cell lung cancer (NSCLC) patients. ARHGEF5 and
      Src have been shown to play an important role in tumorigenesis. However, the
      involvement of ARHGEF5 and Src in NSCLC remains unknown. Therefore, we evaluated
      the expression of ARHGEF5 and Src in resected NSCLC tissues and the correlation
      of co-expression of ARHGEF5 and Src and the prognosis of patients with resected
      NSCLC. Positive expression of ARHGEF5 was detected in 133 cases of 193 patients
      (68.91%). A total of 193 NSCLC patients (male: 145; female: 48; average age:
      61.84 years; age range: 31-84) were enrolled in this study, of which 99 cases
      were squamous cell carcinomas (SCCs) (51.30%) and 94 cases were adenocarcinomas
      (ADCs) (48.70%). The expression of ARHGEF5 was mainly located in the cytoplasm of
      tumor cells, but not in the corresponding adjacent lung tissues. The levels of
      ARHGEF5 were significantly associated with age, differentiation and tumor stage.
      ARHGEF5 protein expression was associated with Src protein expression in NSCLC
      (chi(2) = 11.874, P<0.01) and in ADC (chi(2) = 12.194, P<0.01), but not in SCC.
      Co-immunoprecipitation revealed that there was a physical interaction between Src
      and ARHGEF5 in lung cancer cells. The patients with ARHGEF5(+)/Src(+) had a
      shorter survival time compared with the other patients (29.37 months versus 39.90
      months, P = 0.029). In conclusion, ARHGEF5/Src can be considered as a prognostic
      biomarker and a therapeutic target for patients with resected NSCLC.

PMID- 24126925
TI  - Specificity of psychosis, mania and major depression in a contemporary family
      study.
AB  - There has been increasing attention to the subgroups of mood disorders and their
      boundaries with other mental disorders, particularly psychoses. The goals of the
      present paper were (1) to assess the familial aggregation and co-aggregation
      patterns of the full spectrum of mood disorders (that is, bipolar,
      schizoaffective (SAF), major depression) based on contemporary diagnostic
      criteria; and (2) to evaluate the familial specificity of the major subgroups of
      mood disorders, including psychotic, manic and major depressive episodes (MDEs).
      The sample included 293 patients with a lifetime diagnosis of SAF disorder,
      bipolar disorder and major depressive disorder (MDD), 110 orthopedic controls,
      and 1734 adult first-degree relatives. The diagnostic assignment was based on all
      available information, including direct diagnostic interviews, family history
      reports and medical records. Our findings revealed specificity of the familial
      aggregation of psychosis (odds ratio (OR)=2.9, confidence interval (CI): 1.1
      7.7), mania (OR=6.4, CI: 2.2-18.7) and MDEs (OR=2.0, CI: 1.5-2.7) but not
      hypomania (OR=1.3, CI: 0.5-3.6). There was no evidence for cross-transmission of
      mania and MDEs (OR=.7, CI:.5-1.1), psychosis and mania (OR=1.0, CI:.4-2.7) or
      psychosis and MDEs (OR=1.0, CI:.7-1.4). The strong familial specificity of
      psychotic, manic and MDEs in this largest controlled contemporary family study
      challenges the growing assertion that the major types of mood disorders are
      manifestations of a common underlying diathesis. 

PMID- 24126924
TI  - A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced
      fear.
AB  - Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the
      bodily responses to stressors, yet there is no clear relationship between the
      levels of these hormones and stress-associated mental illnesses such as
      posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be
      involved in this effect of stress. Here we used a rodent model of PTSD in which
      rats repeatedly exposed to a stressor display heightened fear learning following
      auditory Pavlovian fear conditioning. Our results show that stress-related
      increases in circulating ghrelin, a peptide hormone, are necessary and sufficient
      for stress-associated vulnerability to exacerbated fear learning and these
      actions of ghrelin occur in the amygdala. Importantly, these actions are also
      independent of the classic HPA stress axis. Repeated systemic administration of a
      ghrelin receptor agonist enhanced fear memory but did not increase either
      corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala
      infusion of a ghrelin receptor agonist produced a similar enhancement of fear
      memory. Ghrelin receptor antagonism during repeated stress abolished stress
      related enhancement of fear memory without blunting stress-induced corticosterone
      release. We also examined links between ghrelin and growth hormone (GH), a major
      downstream effector of the ghrelin receptor. GH protein was upregulated in the
      amygdala following chronic stress, and its release from amygdala neurons was
      enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in
      the amygdala was also sufficient to increase fear. Finally, virus-mediated
      overexpression of a GH receptor antagonist was sufficient to block the fear
      enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin
      requires GH in the amygdala to exert fear-enhancing effects. These results
      suggest that ghrelin mediates a novel branch of the stress response and highlight
      a previously unrecognized role for ghrelin and growth hormone in maladaptive
      changes following prolonged stress. 

PMID- 24126926
TI  - Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia
      and autism spectrum disorders.
AB  - Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex
      neurodevelopmental disorders that may share an underlying pathology suggested by
      shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147
      ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes
      were primarily selected for their function in the synapse and were categorized
      as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate
      Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors
      and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function
      (LoF) variants that are predicted to severely disrupt protein-coding sequence
      were detected among 2 861 rare variants. We found an excess of LoF variants in
      the combined cases compared with controls (P=0.02). This effect was stronger when
      analysis was limited to singleton LoF variants (P=0.0007) and the excess was
      present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category,
      Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in
      cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was
      identified in an ASD case adding to the growing evidence that this is an
      important risk gene for the disorder. These data support synapse formation and
      maintenance as key molecular mechanisms for SZ and ASD. 

PMID- 24126927
TI  - Role of brain transmigrating neutrophils in depression-like behavior during
      systemic infection.
AB  - Peripheral inflammation induces transmigration of interleukin (IL)-1beta
      expressing neutrophils to the brain. We investigated the possibility that this
      presents a new route of immune-to-brain communication by assessing their role in
      sickness behaviors relevant for mood disorders. Mice treated with
      lipopolysaccharide (LPS) developed despair-like behavior, and administration of
      an anti-polymorphonuclear antibody abolished LPS-induced despair-like and asocial
      behaviors, which correlated with the levels of IL-1beta expression in the brain.
      These behavioral changes were directly mediated by the energy-regulating hormone,
      leptin. Increasing the concentration of endogenous leptin during obesity
      exacerbated, whereas its neutralization using a specific antiserum attenuated
      sickness behaviors and importantly the neutrophil transmigrating process. Our
      results indicate a role for peripheral neutrophils in conveying inflammatory
      signals to the brain, which appears to be dependent on the energy status of the
      organism. This constitutes a novel mechanism of immune-to-brain communication
      relevant to mood disorders.

PMID- 24126928
TI  - Life events: a complex role in the timing of suicidal behavior among depressed
      patients.
AB  - Suicidal behavior is often conceptualized as a response to overwhelming stress.
      Our model posits that given a propensity for acting on suicidal urges, stressors
      such as life events or major depressive episodes (MDEs) determine the timing of
      suicidal acts. Depressed patients (n=415) were assessed prospectively for suicide
      attempts and suicide, life events and MDE over 2 years. Longitudinal data were
      divided into 1-month intervals characterized by MDE (yes/no), suicidal behavior
      (yes/no) and life event scores. Marginal logistic regression models were fit,
      with suicidal behavior as the response variable and MDE and life event score in
      either the same or previous month, respectively, as time-varying covariates.
      Among 7843 person-months, 33% had MDE and 73% had life events. MDE increased the
      risk for suicidal behavior (odds ratio (OR)=4.83, P?0.0001). Life event scores
      were unrelated to the timing of suicidal behavior (OR=1.06 per 100 point
      increase, P=0.32), even during a MDE (OR=1.12, P=0.15). However, among those
      without borderline personality disorder (BPD), both health- and work-related life
      events were key precipitants, as was recurrent MDE, with a 13-fold effect. The
      relationship of life events to suicidal behavior among those with BPD was more
      complex. Recurrent MDE was a robust precipitant for suicidal behavior, regardless
      of BPD comorbidity. The specific nature of life events is key to understanding
      the timing of suicidal behavior. Given unanticipated results regarding the role
      of BPD and study limitations, these findings require replication. Of note, that
      MDE, a treatable risk factor, strongly predicts suicidal behaviors is cause for
      hope. 

PMID- 24126929
TI  - BDNF-TrkB signaling through Erk1/2 MAPK phosphorylation mediates the enhancement
      of fear memory induced by glucocorticoids.
AB  - Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC)
      enhances contextual fear memories through the activation of the Erk1/2(MAPK)
      signaling pathway. However, the molecular mechanism mediating this effect of GC
      remains unknown. Here we used complementary molecular and behavioral approaches
      in mice and rats and in genetically modified mice in which the GR was
      conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling
      pathway as the upstream molecular effectors of GR-mediated phosphorylation of
      Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These
      findings complete our knowledge of the molecular cascade through which GC enhance
      contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK)
      signaling pathways as one of the core effectors of stress-related effects of GC.

PMID- 24126930
TI  - Independence of familial transmission of mania and depression: results of the
      NIMH family study of affective spectrum disorders.
AB  - The goal of this study is to investigate the familial transmission of the
      spectrum of bipolar disorder in a nonclinical sample of probands with a broad
      range of manifestations of mood disorders. The sample included a total of 447
      probands recruited from a clinically enriched community screening and their 2082
      adult living and deceased first-degree relatives. A best estimate diagnostic
      procedure that was based on either direct semistructured interview or structured
      family history information from multiple informants regarding non-interviewed
      relatives was employed. Results revealed that there was specificity of familial
      aggregation of bipolar I (BP I; odds ratio (OR)=8.40; 3.27-20.97; h2=0.83) and
      major depressive disorder (OR=2.26; 1.58-3.22; h2=0.20), but not BP II. The
      familial aggregation of BP I was primarily attributable to the familial
      specificity of manic episodes after adjusting for both proband and relative
      comorbid anxiety and substance use disorders. There was no significant cross
      aggregation between mood disorder subtypes suggesting that the familial
      transmission of manic and major depressive episodes is independent despite the
      high magnitude of comorbidity between these mood states. These findings confirm
      those of earlier studies of the familial aggregation of bipolar disorder and
      major depression in the first nonclinical sample, and the largest family study of
      bipolar disorder in the USA using contemporary nonhierarchical diagnostic
      criteria for mood and anxiety disorders. The results suggest that these major
      components of bipolar disorder may represent distinct underlying pathways rather
      than increasingly severe manifestations of a common underlying diathesis.
      Therefore, dissection of the broad bipolar phenotype in genetic studies could
      actually generate new findings that could index novel biologic pathways
      underlying bipolar disorder. 

PMID- 24126932
TI  - A survey of rare coding variants in candidate genes in schizophrenia by deep
      sequencing.

PMID- 24126931
TI  - Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant
      efficacy with minimal psychotomimetic adverse effects.
AB  - Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been
      found to induce rapid and robust antidepressant-like effects in rodent models and
      in treatment-refractory depressed patients. However, the marked acute
      psychological side effects of ketamine complicate the interpretation of both
      preclinical and clinical data. Moreover, the lack of controlled data
      demonstrating the ability of ketamine to sustain the antidepressant response with
      repeated administration leaves the potential clinical utility of this class of
      drugs in question. Using quantitative electroencephalography (qEEG) to
      objectively align doses of a low-trapping NMDA channel blocker, AZD6765
      (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel
      blockers to produce antidepressant efficacy without psychotomimetic and
      dissociative side effects. Furthermore, using placebo-controlled data, we show
      that the antidepressant response to NMDA channel blockers can be maintained with
      repeated and intermittent drug administration. Together, these data provide a
      path for the development of novel glutamatergic-based therapeutics for treatment
      refractory mood disorders. 

PMID- 24126933
TI  - Microscale investigations of the fate of heavy metals associated to iron-bearing
      particles in a highly polluted stream.
AB  - As it flows through a dense steelmaking area, the Fensch River does transport
      iron-rich particles and colloids, displaying high contents in metallic
      contaminants (Zn, Cr, Pb, Cu, Ni, and As). Chemical analysis using inductively
      coupled plasma mass spectrometry (ICP-MS) was carried out on three compartments
      waters, suspended materials, and sediments-along the river linear. The variations
      of metallic trace element concentrations along the river were shown to be
      partially related to external inputs (industrial and domestic wastewaters and
      urban surfaces leaching). However, some discrepancies of element partitioning
      were evidenced. Pb, Cu, and Mn tend to concentrate in suspended particulate and
      in dissolved fraction, while Cr and As follow the trend of Fe and concentrate
      within sediments of the most downstream station, just before the junction with
      Moselle waters. Zn appears strongly associated to iron-rich particles, resulting
      in a decrease of its concentration in waters for the last station. Along the
      Fensch linear, the variation of metal partitioning between water and particulate
      phases is accompanied with strong modifications of the nature and mineralogy of
      iron-rich particles, as evidenced by microanalyses using electron and X-ray
      beams. The combination of bulk analyses using ICP-MS and microanalyses applied to
      the three compartments allowed us to propose a three-step process "settling
      weathering-resuspension" to explain Zn partitioning. 

PMID- 24126934
TI  - Solubilization of municipal sewage waste activated sludge by novel lytic
      bacterial strains.
AB  - Extracellular polymeric substances (EPS) are an extracellular matrix found in
      sludge which plays a crucial role in flocculation by interacting with the organic
      solids. Therefore, to enhance pretreatment of sludge, EPS have to be removed. In
      this study, EPS were removed with a chemical extractant, NaOH, to enhance the
      bacterial pretreatment. A lysozyme secreting bacterial consortium was isolated
      from the waste activated sludge (WAS). The result of density gradient gel
      electrophoresis (DGGE) analysis revealed that the isolated consortium consists of
      two strains. The two novel strains isolated were named as Jerish03 (NCBI
      accession number KC597266) and Jerish 04 (NCBI accession number KC597267) and
      they belong to the genus Bacillus. Pretreatment with these novel strains enhances
      the efficiency of the aerobic digestion of sludge. Sludge treated with the
      lysozyme secreting bacterial consortium produced 29 % and 28.5 % increase in
      suspended solids (SS) reduction and chemical oxygen demand (COD) removal compared
      to the raw activated sludge (without pretreatment) during aerobic digestion. It
      is specified that these two novel strains had a high potential to enhance WAS
      degradation efficiency in aerobic digestion.

PMID- 24126936
TI  - Effect of age on the risk of Fever and seizures following immunization with
      measles-containing vaccines in children.
AB  - IMPORTANCE The first dose of live attenuated measles-containing vaccines is
      associated with an increased risk of febrile seizures 7 to 10 days following
      immunization among 12- to 23-month-old children. The combination measles, mumps,
      rubella, and varicella vaccine is associated with a 2-fold increased risk of
      febrile seizures 7 to 10 days following immunization compared with the separately
      administered measles, mumps, and rubella and varicella vaccines. It is unknown
      whether the magnitude of these increased risks depends on age at immunization.
      OBJECTIVE To examine the potential modifying effect of age on the risk of fever
      and seizures following immunization with measles-containing vaccines. DESIGN,
      SETTING, AND PARTICIPANTS Retrospective cohort study at 8 Vaccine Safety Datalink
      sites of a total of 840,348 children 12 to 23 months of age who had received a
      measles-containing vaccine from 2001 through 2011. EXPOSURES Any measles
      containing vaccines and measles-containing vaccines by type. MAIN OUTCOMES AND
      MEASURES Fever and seizure events occurring during a 42-day postimmunization
      observation period. RESULTS In the analysis of any measles-containing vaccines,
      the increased risk of seizures during the 7- to 10-day risk interval, using the
      remainder of the observation period as the control interval, was significantly
      greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable
      risk, 9.5 excess cases per 10,000 doses; 95% CI, 7.6-11.5) than among younger
      children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess
      cases per 10,000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization
      fever was significantly greater among older children than among younger children;
      however, its attributable risk was not. In the analysis of vaccine type, measles,
      mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in
      the risk of fever and 2-fold increase in the risk of seizures compared with
      measles, mumps, and rubella vaccine administered with or without varicella
      vaccine in both younger and older children. CONCLUSIONS AND RELEVANCE Measles
      containing vaccines are associated with a lower increased risk of seizures when
      administered at 12 to 15 months of age. Findings of this study that focused on
      safety outcomes highlight the importance of timely immunization of children with
      the first dose of measles-containing vaccines.

PMID- 24126937
TI  - Hematological and gill histopathological changes in iridescent shark, Pangasius
      hypophthalmus (Sauvage, 1878) exposed to sublethal diazinon and deltamethrin
      concentrations.
AB  - The effect of two insecticides, diazinon and deltamethrin, was investigated on
      hematological parameters and gill morphology in iridescent shark, Pangasius
      hypophthalmus. Fish were exposed to 0.5 and 1 ppm diazinon as well as 0.015 and
      0.020 ppm deltamethrin over a 7-day period. Both insecticides caused
      leukocytosis, lymphopenia, neutrophilia as well as increases in red blood cell
      (RBC), hematocrit (Ht), hemoglobin (Hb) and mean corpuscular volume (MCV).
      Morphological gill damages were observed in fish exposed to both pesticides. It
      is suggested that diazinon and deltamethrin changed immune function and induced
      gill damages which could be the reason of increase in RBC, Ht, Hb and MCV in
      iridescent shark. 

PMID- 24126938
TI  - Studies on the role of osteopontin-1 in endometrial cancer cell lines.
AB  - BACKGROUND: Osteopontin-1 is a well characterized protein in many tumour
      entities. Multiple roles in the processes invasion, metastasis and angiogenesis
      of tumours are attributed to osteopontin-1. The putative role of osteopontin-1
      has not been characterized for endometrial cancer. MATERIAL AND METHODS: We
      investigated multiple endometrial cancer cell lines for osteopontin-1 mRNA- and
      protein-expression. Osteopontin-1 dependent effects were analysed in vitro by
      siRNA inhibition. RESULTS: All endometrial cell lines expressed osteopontin-1.
      Expression of osteopontin-1 was successfully inhibited by specific siRNA. Cells
      with reduced osteopontin-1 expression showed decreased migration in the Boyden
      chamber assay and invasion was reduced in the wound-healing assay. Osteopontin-1
      seems to play a role in apoptotic processes of endometrial cancer cells.
      Inhibition of osteopontin-1 expression was associated with an increased
      susceptibility for radiation therapy. CONCLUSION: Osteopontin-1 seems to play a
      role in endometrial cancer. Inhibition of osteopontin-1 expression leads to a
      higher susceptibility for radiation therapy. Our results suggest that a reduced
      expression of osteopontin-1 in endometrial cancer could inhibit the development
      of invasion and metastasis in these cells.

PMID- 24126939
TI  - Time management in radiation oncology: evaluation of time, attendance of medical
      staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO
      trial.
AB  - PURPOSE: In order to evaluate resource requirements, the German Society of
      Radiation Oncology (DEGRO) recorded the times needed for core procedures in the
      radio-oncological treatment of various cancer types within the scope of its QUIRO
      trial. The present study investigated the personnel and infrastructural resources
      required in radiotherapy of prostate cancer. METHODS: The investigation was
      carried out in the setting of definitive radiotherapy of prostate cancer patients
      between July and October 2008 at two radiotherapy centers, both with well-trained
      staff and modern technical facilities at their disposal. Personnel attendance
      times and room occupancy times required for core procedures (modules) were each
      measured prospectively by two independently trained observers using time
      measurements differentiated on the basis of professional group (physician,
      physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated
      radiotherapy (IMRT). RESULTS: Total time requirements of 983 min for 3D-cRT and
      1485 min for step-and-shoot IMRT were measured for the technician (in terms of
      professional group) in all modules recorded and over the entire course of
      radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical
      specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the
      physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was
      significant, although variations in time spans occurred primarily as a result of
      various problems during patient treatment. CONCLUSION: This investigation has
      permitted, for the first time, a realistic estimation of average personnel and
      infrastructural requirements for core procedures in quality-assured definitive
      radiotherapy of prostate cancer. The increased time needed for IMRT applies to
      the step-and-shoot procedure with verification measurements for each irradiation
      planning.

PMID- 24126940
TI  - Exploration of miRNA families for hypotheses generation.
AB  - Technological improvements have resulted in increased discovery of new microRNAs
      (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families
      are important because they suggest a common sequence or structure configuration
      in sets of genes that hint to a shared function. Exploratory tools to enhance
      investigation of characteristics of miRNA families and the functions of family
      specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly
      web-based tool that allows customized interrogation and comparisons of miRNA
      families for hypotheses generation, and comparison of per-species chromosomal
      distribution of miRNA genes in different families. This study illustrates
      hypothesis generation using miRNAVISA in seven species. Our results unveil a
      subclass of miRNAs that may be regulated by genomic imprinting, and also suggest
      that some miRNA families may be species-specific, as well as chromosome- and/or
      strand-specific. 

PMID- 24126941
TI  - Quantification of serum SOX2 DNA with FQ-PCR potentially provides a diagnostic
      biomarker for lung cancer.
AB  - Sex-determining region Y-box 2 (SOX2), as a subunit of transcription and
      reprogramming factor, plays a critical role in the development and progression of
      many malignancies, including lung cancer through gene amplification. In the
      present study, we aimed to quantify the levels of serum SOX2 DNA, analyze its
      diagnostic value and compare it with existing clinical parameters in lung cancer,
      and purpose to provide a novel tumor marker for lung cancer. Serum DNA was
      extracted from 94 lung cancer patients, 10 benign lung diseases, and 30 healthy
      volunteers, and then the levels of SOX2 DNA were quantified using real-time
      fluorescent quantitative polymerase chain reaction (FQ-PCR). The data were
      analyzed by statistical software SPSS14.0. The present results show that serum
      SOX2 DNA level in lung cancer group was higher compared to the levels in benign
      lung diseases group (u = 102.0, p < 0.001) or healthy group (u = 140.0, p <
      0.001), and it was closely associated with TNM stage, histopathological type, and
      tumor size (p = 0.031, p = 0.012, and p = 0.010, respectively). However, serum
      SOX2 DNA levels of lung cancer patients were not associated with age, gender,
      smoking status, lymph node metastasis, or tumor differentiation (p > 0.05). ROC
      curve showed a sensitivity of 78.9% and a specificity of 82.5% for the ability of
      serum SOX2 DNA to detect lung cancer at the cutoff value of 1,078.3 copies/ul.
      Furthermore, we assessed the associations of serum SOX2 levels with clinical
      existing lung tumor markers, such as squamous cell carcinoma antigen, cytokeratin
      fragment 21-1, and neuron-specific enolase. The sensitivity was increased from
      24.9, 66.1, and 39.1 to 84.2, 92.8, and 87.5%, respectively, by the combination
      of serum SOX2 DNA. Taken together, quantification of serum SOX2 DNA by FQ-PCR may
      serve as a novel accessory diagnostic tool for the clinical screening and
      detection of lung cancer.

PMID- 24126942
TI  - Biochemical basis of cancer chemoprevention and/or chemotherapy with ginsenosides
      (Review).
AB  - Cancer still imposes a global threat to public health. After decades of research
      on cancer biology and enormous efforts in developing anticancer therapies, we now
      understand that the majority of cancers can be prevented. Bioactive
      phytochemicals present in edible plants have been shown to reduce the risk of
      various types of cancer. Ginseng (Panax ginseng C.A. Meyer), which contains a
      wide variety of saponins, known as ginsenosides, is an age-old remedy for human
      ailments, including cancer. Numerous laboratory-based studies have revealed the
      anticancer properties of ginsenosides, which compel tumor cells to commit
      suicide, arrest the proliferation of cancer cells in culture and inhibit
      experimentally-induced tumor formation in laboratory animals. Ginsenosides have
      been reported to inhibit tumor angiogenesis, as well as the invasion and
      metastasis of various types of cancer cells. Moreover, ginsenosides as
      combination therapy enhance the sensitivity of chemoresistant tumors to
      clinically used chemotherapeutic agents. This review sheds light on the molecular
      mechanisms underlying the cancer chemopreventive and/or chemotherapeutic activity
      of ginsenosides and their intestinal metabolites with particular focus on the
      modulation of cell signaling pathways associated with oxidative stress,
      inflammation, cell proliferation, apoptosis, angiogenesis and the metastasis of
      cancer cells. 

PMID- 24126943
TI  - Efficacy of photodynamic therapy for treatment of basal cell carcinoma in organ
      transplant recipients.
AB  - Photodynamic therapy (PDT) is an established treatment for superficial basal cell
      carcinoma (BCC). Organ transplant recipients (OTRs) are at increased risk of BCC.
      We investigated the efficacy of PDT in OTRs and compared the recurrence rate to
      the non-transplanted population. We conducted a retrospective casenote review of
      all patients undergoing PDT for the treatment of BCC in our centre from 2003 to
      2013. Three hundred and twenty-two BCCs from 103 patients underwent PDT during
      this period. There is no significant difference in BCC recurrence following PDT
      in OTRs (22.6 %) versus non-transplant patients (15.2 %) (p = 0.18). PDT is an
      efficacious treatment for BCC in OTRs with no significant evidence of inferiority
      compared to non-transplanted patients. Our findings require corroboration in a
      larger study. 

PMID- 24126944
TI  - Comparing patient and parent recall of 90-day and 30-day migraine disability
      using elements of the PedMIDAS and an Internet headache diary.
AB  - AIM: The aim of this article is to compare 90-day and 30-day recall of Pediatric
      Migraine Disability Assessment (PedMIDAS) elements and headache frequency against
      daily entries from an Internet headache diary among pediatric patients and their
      parents. METHODS: In a prospective cohort study, patients aged 10-18 years with
      episodic migraine or probable migraine completed a 90-day Internet-based headache
      diary that incorporated PedMIDAS questions. Following the 90-day diary period,
      patients and parents completed modified PedMIDAS instruments to assess 90-day and
      30-day recall. Intraclass correlation coefficients (ICC) were calculated to
      measure recall reliability. The Kruskal-Wallis and Jonckheere-Terpstra tests were
      used to explore recall accuracy as it relates to each participant's self-reported
      confidence in recall and to patient age. RESULTS: Fifty-two subjects completed 90
      consecutive diary entries. Comparing 30-day to 90-day recall of PedMIDAS
      elements, ICC scores improved by 26.2% (patients) and 17.5% (parents). Patients
      had better recall than their parents for all study measures. Self-reported
      confidence in recall and patient age had limited and inconsistent effects on
      recall accuracy. CONCLUSION: The optimal recall interval to assess migraine
      disability must balance recall accuracy with generalizability across a range of
      headache frequencies. When compared to daily diary entries, recall accuracy of
      PedMIDAS elements and headache frequency improves at 30 days compared to 90 days.
      Parent report of migraine disability should not be used as a replacement for
      patient report.

PMID- 24126945
TI  - Stimulation of dural vessels excites the SI somatosensory cortex of the cat via a
      relay in the thalamus.
AB  - AIM: We carried out experiments in cats to determine the thalamo-cortical
      projection sites of trigeminovascular sensory neurons. METHODS: 1) We stimulated
      the middle meningeal artery (MMA) with C-fibre intensity electrical shocks and
      made field potential recordings over the somatosensory cortical surface. 2) We
      then recorded neurons in the ventroposteromedial (VPM) nucleus of the thalamus in
      search of neurons which could be activated from the skin, MMA and superior
      sagittal sinus. 3) Finally, we attempted to antidromically activate the neurons
      found in stage 2 by stimulating the responsive cortical areas revealed in stage
      1. RESULTS: VPM neurons received trigeminovascular input, input from the V1
      facial skin and could also be activated by electrical stimulation of the
      somatosensory cortex. VPM neurons activated from the cortex responded with short
      and invariant latencies (6.7 +/- 7.7 msec mean and SD). They could follow high
      rates of stimulation and sometimes showed collision with orthodromic action
      potentials. CONCLUSIONS: We conclude that somatosensory (SI) cortical stimulation
      excites trigeminovascular VPM neurons antidromically. In consequence, these VPM
      neurons project to the somatosensory cortex. These findings may help to explain
      the ability of migraineurs with headache in the trigeminal distribution to
      localise their pain to a particular region in this distribution.

PMID- 24126946
TI  - Prevalence and clinical characteristics of headache in adolescents: a Croatian
      epidemiological study.
AB  - BACKGROUND: Headaches are often under-diagnosed in adolescents. The aim of this
      study was to examine the one-year prevalence of primary headaches among high
      school students in the city of Zagreb, the capital of Croatia. METHODS: This was
      a population-based, cross-sectional study. A total of 2350 questionnaires
      consisting of questions on demographic data, the presence and clinical
      characteristics of headaches were distributed among students in eight high
      schools; 2057 (87.5%) questionnaires were eligible for analysis. RESULTS: The
      mean age of the students was 17.2 +/- 1.2 years; 50.2% were female. The
      prevalence of recurrent headache was 30.1% (620/2057), girls 35.1%, boys 25.2%.
      Among students with headache, 291 (46.9%) had migraine, and 329 (53.1%) had
      tension-type headaches (TTHs). The mean frequency of headaches was 5.66 per month
      in girls and 4.42 in boys; mean duration of a headache attack was 8.94 hours in
      girls and 8.37 hours in boys (NS). Unilateral headache was present in 31.6%,
      throbbing quality in 22.6%, dull in 34.4% of students; 22.4% had severe intensity
      and 70.3% moderate. Nausea was present in 4.0% always and in 14.7% frequently
      (girls 18.8%), photophobia in 41.3%, phonophobia in 63.2%, osmophobia in 23.9%
      (NS among genders). Almost 30% of students were disabled and stayed at home, more
      frequently boys. Girls (33.4%) were more likely to take drugs for every attack;
      number per month was 3.7. The results of this study showed that the prevalence of
      migraine among adolescents in Croatia was 16.5% for girls and 11.8% for boys; the
      prevalence of TTH was 18.4% for girls and 13.4% for boys. CONCLUSIONS: The
      prevalence of self-reported headache among high school students in Zagreb is
      relatively high. Significant gender differences in frequency and clinical
      characteristics were observed. Primary headaches among adolescents are an
      important public health problem and should receive more attention from school and
      health authorities.

PMID- 24126947
TI  - Cytotoxic T-lymphocyte-associated antigen-4 polymorphisms and susceptibility to
      cervical cancer: a meta-analysis.
AB  - Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) polymorphisms have been
      examined for associations with cervical cancer in various countries. The results,
      however, are inconclusive. The present study aimed to explore whether CTLA-4 +49
      A/G, -318 C/T and CT60 G/A polymorphisms confer susceptibility to cervical
      cancer. A meta-analysis was performed with 7,794 subjects included in 15 case
      control studies that were published up to January 1, 2013. The results from the
      meta-analysis indicated that there were no significant associations between the
      risk of cervical cancer and the three studied polymorphisms [+49 A/G: Odds ratio
      (OR), 0.94 and 95% confidence interval (CI), 0.82-1.07 for GG+AG vs. AA; -318
      C/T: OR, 1.33 and 95% CI, 0.82-2.16 for TT+TC vs. CC; and CT60: OR, 0.98 and 95%
      CI, 0.72-1.33 for AA+AG vs. GG]. Stratified analyses by ethnicity for the +49 A/G
      and -318 C/T polymorphisms suggested that Asian populations had a decreased risk
      of cervical cancer for the +49 A/G polymorphism (OR, 0.75 and 95% CI, 0.58-0.97
      for GG+AG vs. AA), but an increased risk for the -318 C/T polymorphism (OR, 2.02
      and 95% CI, 1.36-3.00 for TC vs. CC). In summary, the current meta-analysis
      showed that the +49 A/G and -318 C/T polymorphisms in CTLA-4 constitute risk
      factors for cervical cancer.

PMID- 24126949
TI  - Hydrodeoxygenation by deuterium gas--a powerful way to provide insight into the
      reaction mechanisms.
AB  - This study demonstrates the use of isotopic labelling and NMR to study the HDO
      process. As far as we know, this is the first reported effort to trace the
      incorporation of hydrogen in the HDO process of lignin pyrolysis oil thereby
      providing key fundamental insight into its reaction mechanism. 

PMID- 24126950
TI  - Practical guidance for charting ethics consultations.
AB  - It is generally accepted that appropriate documentation of activities and
      recommendations of ethics consultants in patients' medical records is critical.
      Despite this acceptance, the bioethics literature is largely devoid of guidance
      on key elements of an ethics chart note, the degree of specificity that it should
      contain, and its stylistic tenor. We aim to provide guidance for a variety of
      persons engaged in clinical ethics consultation: new and seasoned ethics
      committee members who are new to ethics consultation, students and trainees in
      clinical ethics, and those who have significant experience with ethics
      consultation so that they can reflect on their practice. Toward the goal of
      promoting quality charting practices in ethics consultations, we propose
      recommendations on a broad array of questions concerning clinical ethics
      consultation chart notes, including whether and when to write a chart note, and
      practical considerations for the tenor, purpose, and content of a chart note. Our
      broader aim is to promote discussion about good charting practices in clinical
      ethics, with the hope of contributing to clear standards of excellence in
      clinical ethics consultation. 

PMID- 24126951
TI  - [Implementation of a patient data management system. Effects on intensive care
      documentation].
AB  - BACKGROUND: Patient data management systems (PDMS) enable digital documentation
      on intensive care units (ICU). A commercial PDMS was implemented in a 25-bed ICU
      replacing paper-based patient charting. The ICU electronic patient record is
      completely managed inside the PDMS. It compiles data from vital signs monitors,
      ventilators and further medical devices and facilitates some drug dose and fluid
      balance calculations as well as data reuse for administrative purposes.
      Ventilation time and patient severity scoring as well as coding of diagnoses and
      procedures is supported. Billing data transferred via interface to the central
      billing system of the hospital. Such benefits should show in measurable
      parameters, such as documented ventilator time, number of coded diagnoses and
      procedures and others. These parameters influence reimbursement in the German DRG
      system. Therefore, measurable changes in cost and reimbursement data of the ICU
      were expected. MATERIAL AND METHODS: A retrospective analysis of documentation
      quality parameters, cost data and mortality rate of a 25-bed surgical ICU within
      a German university hospital 3 years before (2004-2006) and 5 years after (2007
      2011) PDMS implementation. Selected parameters were documented electronically,
      consistently and reproducibly for the complete time span of 8 years including
      those years where no electronic patient recording was available. The following
      parameters were included: number of cleared DRG, cleared ventilator time, case
      mix (CM), case mix index (CMI), length of stay, number of coded diagnoses and
      procedures, detailed overview of a specific procedure code based on daily Apache
      II and TISS Core 10 scores, mortality, total ICU costs and revenues and partial
      profits for specific ICU procedures, such as renal replacement therapy and blood
      products. RESULTS: Systematic shifts were detected over the study period, such as
      increasing case numbers and decreasing length of stay as well as annual
      fluctuations in severity of disease seen in the CM and CMI. After PDMS
      introduction, the total number of coded diagnoses increased but the proportion of
      DRG relevant diagnoses dropped significantly. The number of procedures increased
      (not significantly) and the number of procedures per case did not rise
      significantly. The procedure 8-980 showed a significant increase after PDMS
      introduction whereas the DRG-relevant proportion of those procedures dropped
      insignificantly. The number of ventilator-associated DRG cases as well as the
      total ventilator time increased but not significantly. Costs and revenues
      increased slightly but profit varied considerably from year to year in the 5
      years after system implementation. A small increase was observed per case, per
      nursing day and per case mix point. Additional revenues for specific ICU
      procedures increased in the years before and dropped after PDMS implementation.
      There was an insignificant increase in ICU mortality rate from 7.4 % in the year
      2006 (before) to 8.5 % in 2007 (after PDMS implementation). In the following
      years mortality dropped below the base level. CONCLUSION: The implementation of
      the PDMS showed only small effects on documentation of reimbursement-relevant
      parameters which were too small to set off against the total investment. The
      method itself, a long-term follow-up of different parameters proved successful
      and can be adapted by other organizations. The quality of results depends on the
      availability of long-term parameters in good quality. No significant influence of
      PDMS on mortality was found.

PMID- 24126952
TI  - Leptin and its receptor expression in dental and periodontal tissues of primates.
AB  - Leptin and its receptor (OBR) have attracted much attention since their
      discovery. They have been reported to play central roles in energy balance, the
      immune-inflammatory response and bone metabolism. Evidence indicates that leptin
      and OBR are associated with inflammatory diseases of dental and periodontal
      tissues. The first step for establishing this is to determine the expression of
      leptin and OBR in these tissues. Our study is the first to examine systematically
      the expression of leptin and OBR in dental and periodontal tissues of monkeys
      (Macaca fascicularis) by immunohistochemistry and in primary cultured cells,
      isolated from human dental and periodontal tissues, by reverse transcription plus
      the polymerase chain reaction and immunocytochemistry. Our results show that
      leptin and OBR are constitutively expressed and widely distributed in dental and
      periodontal tissues of primates. Their immunoreaction is especially strong in
      junctional epithelium, a unique front-line defense around teeth and in
      mineralizing areas of the dental pulp and periodontal ligament. The expression of
      the long and also functional form of OBR (OBRb) indicates that leptin has a
      direct effect on these cells. Thus, we can reasonably infer that leptin and OBR
      exert effects on defense, mineralization and angiogenesis in dental and
      periodontal tissues of primates. 

PMID- 24126948
TI  - Multiple courses of antenatal corticosteroids for preterm birth study: outcomes
      in children at 5 years of age (MACS-5).
AB  - IMPORTANCE: A single course of antenatal corticosteroid therapy is recommended
      for pregnant women at risk of preterm birth between 24 and 33 weeks' gestational
      age. However, 50% of women remain pregnant 7 to 14 days later, leading to the
      question of whether additional courses should be given to women remaining at risk
      for preterm birth. The Multiple Courses of Antenatal Corticosteroids for Preterm
      Birth Study (MACS) was an international randomized clinical trial that compared
      multiple courses of antenatal corticosteroids with a single course in women at
      risk of preterm birth. OBJECTIVE: To determine the effects of single vs multiple
      courses of antenatal corticosteroid therapy on death or neurodevelopmental
      disability (neuromotor, neurosensory, or neurocognitive/neurobehavioral function)
      at 5 years of age in children whose mothers participated in MACS. Our secondary
      aims were to determine the effect on height, weight, head circumference, blood
      pressure, intelligence, and specific cognitive (visual, spatial, and language)
      skills. DESIGN, SETTING, AND PARTICIPANTS: Cohort follow-up study of children
      seen between June 2006 and May 2012 at 55 centers. In total, 1724 women (2141
      children) were eligible for the study, of whom 1728 children (80.7% of the 2141
      eligible children) participated and 1719 children contributed to the primary
      outcome. INTERVENTION: Single and multiple courses of antenatal corticosteroid
      therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was death or survival
      with a neurodevelopmental disability in 1 of the following domains: neuromotor
      (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for
      visual/hearing aids), or neurocognitive/neurobehavioral function (abnormal
      attention, memory, or behavior). RESULTS: There was no significant difference
      between the groups in the risk of death or neurodevelopmental disability: 217 of
      871 children (24.9%) in the multiple-courses group vs 210 of 848 children (24.8%)
      in the single-course group (odds ratio, 1.02 [95% CI, 0.81 to 1.29]; P = .84).
      CONCLUSIONS AND RELEVANCE: Multiple courses, compared with a single course, of
      antenatal corticosteroid therapy did not increase or decrease the risk of death
      or disability at 5 years of age. Because of a lack of strong conclusive evidence
      of short-term or long-term benefits, it remains our opinion that multiple courses
      not be recommended in women with ongoing risk of preterm birth. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00187382.

PMID- 24126953
TI  - Proteome wide reduction in AGE modification in streptozotocin induced diabetic
      mice by hydralazine mediated transglycation.
AB  - The non-enzymatic reaction between glucose and protein can be chemically reversed
      by transglycation. Here we report the transglycation activity of hydralazine
      using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated
      transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in
      streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein
      glycation, as well as presence of hydralazine-glucose conjugate in urine of
      diabetic mice treated with hydralazine. Hydralazine down regulated the expression
      of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and
      super oxide dismutase (SOD). These findings will provide a new dimension for
      developing intervention strategies for the treatment of glycation associated
      diseases such as diabetes complications, atherosclerosis, and aging. 

PMID- 24126954
TI  - Fate of ventricular and valve performance following early bidirectional Glenn
      procedure after Norwood operation controlled for hypoplastic left heart syndome
      anatomic subtype.
AB  - The Norwood operation (NO) with a right ventricle (RV)-to-pulmonary artery (PA)
      shunt (NRVPA) is reportedly associated with early hemodynamic advantage. Shunt
      strategy has been implicated in ventricular function. Outcomes after NRVPA
      compared with classic procedure as part of a strategy involving early
      bidirectional Glenn (BDG) procedure were analyzed with reference to RV,
      tricuspid, and neoaortic valve performance. Between January 2005 and December
      2010, 128 neonates with hypoplastic left heart syndrome (HLHS) underwent NO.
      Controlled for aortic/mitral stenosis (AS-MS) subtype, 28 patients underwent
      NRVPA (group A), and 26 patients had classic procedure (group B). The patients
      with a non-HLHS single-ventricle anatomy and those who had undergone a hybrid
      approach for HLHS were excluded from the study. The mean age at NO was 6.8 +/-
      3.5 days in group A and 6.9 +/- 3.6 days in group B. Transthoracic
      echocardiographic evaluation (TTE) after NO (TTE-1) at the midinterval between NO
      and BDG (TTE-2), before BDG (TTE-3), before Fontan (TTE-4), and at the last
      follow-up evaluation (TTE-5) was undertaken. Cardiac catheterization was used to
      assess hemodynamic parameters before the Glenn and Fontan procedures. The
      operative, interstage, and pre-Fontan survival rates for AS-MS after NO were
      respectively 88.1 % (90.3 % in group A vs. 84.7 % in group B; p = 0.08), 82.5 %
      (82.7 % in group A vs. 81.8 % in group B; p = 0.9), and 80.7 % (79.5 % in group A
      vs. 81.8 % in group B; p = 0.9). The median follow-up period was 39.6 months
      (interquartile range 2.7-4.9 months). The RV global function, mid- and
      longitudinal indexed dimensions, fractionated area change before BDG (TTE-1, TTE
      2, TTE-3) and after BDG (TTE-4, TTE-5), and right ventricular end-diastolic
      pressure did not differ statistically between the groups (p > 0.05). No
      statistically significant difference in tricuspid or neoaortic intervention was
      found between the groups (p > 0.05). Controlled for the AS-MS HLHS subtype, shunt
      strategy showed no midterm survival or hemodynamic (ventricular or valve) impact.
      At midterm, the follow-up need for neoaortic or tricuspid valve surgical
      intervention was not affected by shunt selection. The structural ventricular
      adaptation after reversal of shunt physiology was irrespective of shunt strategy.

PMID- 24126955
TI  - Author reply to comment on "atorvastatin safety in Kawasaki disease patients with
      coronary artery aneurysms".

PMID- 24126956
TI  - Stricter rules and powers will help prevent another NHS scandal, says CQC chief.

PMID- 24126957
TI  - UK should adopt cheap methods of healthcare delivery from poorer countries.

PMID- 24126959
TI  - Providing high quality of care drives physician satisfaction, US study says.

PMID- 24126958
TI  - EMA confirms that hydroxyethyl starch solutions should not be used in critically
      ill, sepsis, or burns patients.

PMID- 24126961
TI  - Regulation of neuronal toxicity of beta-amyloid oligomers by surface ATP
      synthase.
AB  - Alzheimer disease (AD) is characterized by the accumulation of amyloid-beta
      (Abeta) protein and intracellular neurofibrillary tangles. Previous studies have
      shown that Abeta aggregation is one of the most important initiating factors in
      the pathogenesis of AD. Oligomers of Abeta cause neurotoxicity, synaptic
      dysfunction and memory impairments that underlie AD. An increasing number of
      studies have shown that oligomeric Abeta may bind with a number of surface
      proteins to mediate its neuronal toxicity. Previously, it was shown that ATP
      synthase is present on the cell surface and binds with oligomeric Abeta. In the
      present study, ATP synthase was confirmed to be present on the surface of neurons
      and oligomeric Abeta was observed to induce neuron damage and expression of
      amyloid precursor protein (APP) and Fe65 increase. Results showed that inhibition
      of surface ATP synthase may reduce the neuronal damage by LDH release assay and
      decrease APP and Fe65 expression by immunofluorescence and western blot analysis.
      These results confirmed that the cell surface ATP synthase is a binding protein
      for Abeta on neural cells and suggested that the surface ATP synthase may be
      involved in the neurotoxic effects of oligomeric Abeta and may be an intervening
      target of pathogenesis of AD.

PMID- 24126962
TI  - The role of apoptosis in immune hyporesponsiveness following AAV8 liver gene
      transfer.
AB  - Gene therapy provides a significant opportunity to treat a variety of inherited
      and acquired diseases. However, adverse immune responses toward the adeno
      associated virus (AAV) antigens may limit its success. The mechanisms responsible
      for immunity or tolerance toward AAV-encoded transgene products remain poorly
      defined. Studies in mice demonstrate that AAV2/8 gene transfer to liver is
      associated with immunological hyporesponsiveness toward both AAV vector and
      antigenic transgene product. To evaluate the role of activation-induced cell
      death (AICD) and cytokine withdrawal (intrinsic cell death) in the deletion of
      mature T lymphocytes, we compared immunological responses in hepatic AAV2/8
      transfer in murine recipients lacking the Fas receptor, and recipients
      overexpressing Bcl-xL, to WT murine counterparts. Prolonged transgene expression
      was dependent on both Fas signaling and Bcl-xL-regulated apoptosis in T cells.
      Abrogation of intrinsic cell death enhanced Th1 responses, whereas AICD
      functioned to limit neutralizing antibody production toward AAV2/8. In addition,
      immune hyporesponsiveness and stable transgene expression was dependent on
      upregulation of FasL expression on transduced hepatocytes and a corresponding
      apoptosis of infiltrating Fas (+) cells. These data provide evidence that both
      AICD and apoptosis due to cytokine withdrawal of lymphocytes are essential for
      immune hyporesponsiveness toward hepatic AAV2/8-encoded transgene product in the
      setting of liver gene transfer.

PMID- 24126964
TI  - Fatty acid mobilization and comparison to milk fatty acid content in northern
      elephant seals.
AB  - A fundamental feature of the life history of true seals, bears and baleen whales
      is lactation while fasting. This study examined the mobilization of fatty acids
      from blubber and their subsequent partitioning into maternal metabolism and milk
      production in northern elephant seals (Mirounga angustirostris). The fatty acid
      composition of blubber and milk was measured in both early and late lactation.
      Proportions of fatty acids in milk and blubber were found to display a high
      degree of similarity both early and late in lactation. Seals mobilized an
      enormous amount of lipid (~66 kg in 17 days), but thermoregulatory fatty acids,
      those that remain fluid at low temperatures, were relatively conserved in the
      outer blubber layer. Despite the stratification, the pattern of mobilization of
      specific fatty acids conforms to biochemical predictions. Long chain (>20C)
      monounsaturated fatty acids (MUFAs) were the least mobilized from blubber and the
      only class of fatty acids that showed a proportional increase in milk in late
      lactation. Polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs)
      were more mobilized from the blubber, but neither proportion increased in milk at
      late lactation. These data suggest that of the long chain MUFA mobilized, the
      majority is directed to milk synthesis. The mother may preferentially use PUFA
      and SFA for her own metabolism, decreasing the availability for deposition into
      milk. The potential impacts of milk fatty acid delivery on pup diving development
      and thermoregulation are exciting avenues for exploration.

PMID- 24126963
TI  - A review of the multi-level adaptations for maximizing aerobic dive duration in
      marine mammals: from biochemistry to behavior.
AB  - Marine mammals exhibit multi-level adaptations, from cellular biochemistry to
      behavior, that maximize aerobic dive duration. A dive response during aerobic
      dives enables the efficient use of blood and muscle oxygen stores, but it is
      exercise modulated to maximize the aerobic dive limit at different levels of
      exertion. Blood volume and concentrations of blood hemoglobin and muscle
      myoglobin are elevated and serve as a significant oxygen store that increases
      aerobic dive duration. However, myoglobin is not homogeneously distributed in the
      locomotory muscles and is highest in areas that produce greater force and consume
      more oxygen during aerobic swimming. Muscle fibers are primarily fast and slow
      twitch oxidative with elevated mitochondrial volume densities and enhanced
      oxidative enzyme activities that are highest in areas that produce more force
      generation. Most of the muscle mitochondria are interfibriller and homogeneously
      distributed. This reduces the diffusion distance between mitochondria and helps
      maintain aerobic metabolism under hypoxic conditions. Mitochondrial volume
      densities and oxidative enzyme activities are also elevated in certain organs
      such as liver, kidneys, and stomach. Hepatic and renal function along with
      digestion and assimilation continue during aerobic dives to maintain
      physiological homeostasis. Most ATP production comes from aerobic fat metabolism
      in carnivorous marine mammals. Glucose is derived mostly from gluconeogenesis and
      is conserved for tissues such as red blood cells and the central nervous system.
      Marine mammals minimize the energetic cost of swimming and diving through body
      streamlining, efficient, lift-based propulsive appendages, and cost-efficient
      modes of locomotion that reduce drag and take advantage of changes in buoyancy
      with depth. Most dives are within the animal's aerobic dive limit, which
      maximizes time underwater and minimizes recovery time at the surface. The result
      of these adaptations is increased breath-hold duration and enhanced foraging
      ability that maximizes energy intake and minimizes energy output while making
      aerobic dives to depth. These adaptations are the long, evolutionary legacy of an
      aquatic lifestyle that directly affects the fitness of marine mammal species for
      different diving abilities and environments.

PMID- 24126965
TI  - Longer electromechanical delay impairs hamstrings explosive force versus
      quadriceps.
AB  - INTRODUCTION: Explosive neuromuscular performance refers to the ability to
      rapidly increase force in response to neuromuscular activation. The lower
      explosive force production of the hamstrings relative to the quadriceps could
      compromise knee joint stability and increase the risk of anterior cruciate
      ligament injury. However, the time course of the rise in explosive force of the
      hamstrings and quadriceps from their initial activation, and thus the explosive
      hamstrings-to-quadriceps (H/Q) force ratio, has not been documented. METHODS: The
      neuromuscular performance of 20 untrained males was assessed during a series of
      isometric knee flexion and extension contractions, with force and surface EMG of
      the hamstrings and quadriceps recorded during explosive and maximum voluntary
      contractions. Hamstrings force was expressed relative to quadriceps force to
      produce hamstring-to-quadriceps ratios of explosive H/Q force and H/Q maximum
      voluntary force. For the explosive contractions, agonist electromechanical delay
      (EMD), agonist and antagonist neural activation were assessed. RESULTS: The
      quadriceps was 79% stronger than the hamstrings, but quadriceps explosive force
      was up to 480% greater than the hamstrings from 25 to 50 ms after first
      activation. Consequently, the explosive H/Q force ratio was very low at 25 and 50
      ms (0%-17%) and significantly different from H/Q maximum voluntary force ratio
      (56%). Hamstrings EMD was 95% greater than quadriceps EMD (44.0 vs 22.6 ms),
      resulting in a 21-ms later onset of force in the hamstrings that appeared to
      explain the low explosive H/Q force ratio in the early phase of activation.
      CONCLUSIONS: Prolonged hamstrings EMD appears to impair early phase (0-50 ms)
      explosive force production relative to the quadriceps and may render the knee
      unstable and prone to anterior cruciate ligament injury during this period.

PMID- 24126966
TI  - Associations of motor and cardiovascular performance with academic skills in
      children.
AB  - PURPOSE: We investigated the associations of cardiovascular and motor performance
      in grade 1 with academic skills in grades 1-3. METHODS: The participants were 6-
      to 8-yr-old children with complete data in grades 1-2 for 174 children and in
      grade 3 for 167 children. Maximal workload during exercise test was used as a
      measure of cardiovascular performance. The shuttle run test (SRT) time, the
      errors in balance test, and the number of cubes moved in box and block test (BBT)
      were measures of motor performance. Academic skills were assessed using reading
      fluency, reading comprehension, and arithmetic skill tests. RESULTS: Among boys,
      longer SRT time was associated with poorer reading fluency in grades 1-3 (beta = 
      0.29 to -0.39, P < 0.01), reading comprehension in grades 1-2 (beta = -0.25 to 
      0.29, P < 0.05), and arithmetic skills in grades 1-3 (beta = -0.33 to -0.40, P <
      0.003). Poorer balance was related to poorer reading comprehension (beta = -0.20,
      P = 0.042). The smaller number of cubes moved in BBT was related to poorer
      reading fluency in grades 1-2 (beta = 0.23-0.28, P < 0.03), reading comprehension
      in grade 3 (beta = 0.23, P = 0.037), and arithmetic skills in grades 1-2 (beta =
      0.21-0.23, P < 0.043). Among girls, longer SRT time was related to poorer reading
      fluency in grade 3 (beta = -0.27, P = 0.027) and arithmetic skills in grade 2
      (beta = -0.25, P = 0.040). The smaller number of cubes moved in BBT was
      associated with worse reading fluency in grade 2 (beta = 0.26, P = 0.030).
      Cardiovascular performance was not related to academic skills. CONCLUSIONS:
      Poorer motor performance was associated with worse academic skills in children,
      especially among boys. These findings emphasize early identification of children
      with poor motor performance and actions to improve these children's motor
      performance and academic skills during the first school years.

PMID- 24126967
TI  - Interventions to increase physical activity in middle-age women at the workplace:
      a randomized controlled trial.
AB  - PURPOSE: A four-group randomized controlled trial evaluated the impact of
      distinct workplace interventions to increase the physical activity (PA) and to
      reduce anthropometric parameters in middle-age women. METHODS: One-hundred and
      ninety-five women age 40-50 yr who were employees from a university hospital and
      physically inactive at their leisure time were randomly assigned to one of four
      groups: minimal treatment comparator (MTC; n = 47), pedometer-based individual
      counseling (PedIC; n = 53), pedometer-based group counseling (PedGC; n = 48), and
      aerobic training (AT; n = 47). The outcomes were total number of steps (primary
      outcome), those performed at moderate intensity (>= 110 steps per minute), and
      weight and waist circumference (secondary outcomes). Evaluations were performed
      at baseline, at the end of a 3-month intervention, and 3 months after that. Data
      were presented as delta [(after 3 months-baseline) or (after 6 months-baseline)]
      and 95% confidence interval. To detect the differences among the groups, a one
      way ANOVA and a Holm-Sidak post hoc test was used (P < 0.05). The Cohen effect
      size was calculated, and an intention-to-treat approach was performed. RESULTS:
      Only groups using pedometers (PedIC and PedGC) increased the total number of
      steps after 3 months (P < 0.05); however, the increase observed in PedGC group
      (1475 steps per day) was even higher than that in PedIC (512 steps per day, P <
      0.05) with larger effect size (1.4). The number of steps performed at moderate
      intensity also increased only in the PedGC group (845 steps per day, P < 0.05).
      No PA benefit was observed at 6 months. Women submitted to AT did not modify PA
      daily life activity but reduced anthropometric parameters after 3 and 6 months (P
      < 0.05). CONCLUSIONS: Our results show that in the workplace setting, pedometer
      based PA intervention with counseling is effective increasing daily life number
      of steps, whereas AT is effective for weight loss.

PMID- 24126968
TI  - Patients with diabetes in cardiac rehabilitation: attendance and exercise
      capacity.
AB  - PURPOSE: Diabetes increases mortality after myocardial infarction, but
      participation in cardiac rehabilitation (CR) reduces this risk. Our objectives
      were to examine whether attendance at CR and changes in cardiorespiratory fitness
      differed according to diabetic status and sex. METHODS: Retrospective cohort
      study of patients referred for CR in Calgary between 1996 and 2010.
      Cardiorespiratory fitness in metabolic equivalents (METs) was estimated by
      maximal exercise testing at baseline, at the end of the 12-wk CR program, and 1
      yr after CR. RESULTS: Among 7036 nondiabetic and 1546 diabetic patients who
      started, 84.9% of nondiabetic versus 79.5% of diabetic patients completed CR (P <
      0.0001). The difference between diabetic and nondiabetic patients was greater in
      women (81.7% vs 72.1%, P < 0.0001) than that in men (86.0% vs 82.5%, P = 0.004).
      Patients without diabetes were more likely to return for the 1-yr assessment
      (53.7% vs 42.7%, P < 0.0001), and nondiabetic women were more likely than
      diabetic women to attend the 1-yr follow-up (44.3% vs 31.7%, P < 0.0001). Change
      in cardiorespiratory fitness from baseline to 12 wk was +1.0 METs in nondiabetic
      men, +0.9 METS in diabetic men, +0.9 METs in nondiabetic women, and +0.7 METs in
      diabetic women (within-group change; P = 0.0009). Changes in cardiorespiratory
      fitness at 1 yr compared with baseline were +0.9, +0.6, +0.9, and +0.5 METS,
      respectively (within-group change, P = 0.0001). CONCLUSIONS: Patients with
      diabetes, especially females, were less likely than patients without diabetes to
      complete CR and attend follow-up. Among patients who attended 1-yr follow-up,
      changes in cardiorespiratory fitness were not as well maintained in diabetic
      patients as in nondiabetic patients. Identifying barriers and targeting CR
      adherence interventions to patients with diabetes may help improve outcomes.

PMID- 24126969
TI  - Physical activity and improved diastolic function in spinal cord-injured
      subjects.
AB  - PURPOSE: Subjects with spinal cord injury (SCI) have been reported to present
      impaired left ventricular (LV) diastolic function in comparison with able-bodied
      (AB) ones. The present study investigated the effect of regular physical activity
      on the cardiac structure and function of SCI subjects. METHODS: Fifty-eight SCI
      men (29 sedentary [SCI-S] and 29 athletes [SCI-A]) and 29 AB men were cross
      sectionally evaluated by clinical, laboratory, hemodynamic, and echocardiographic
      analysis. All enrolled subjects were normotensive, nondiabetic, nonsmoker, and
      normolipemic, and the studied groups presented similar age and body mass index.
      RESULTS: SCI-S presented similar LV structural and systolic parameters but higher
      E/Em (8.0 +/- 0.5) and lower Em/Am (1.18 +/- 0.09) ratios than SCI-A and AB (E/Em
      = 6.4 +/- 0.3 and 5.9 +/- 0.3, respectively; Em/Am = 1.57 +/- 0.12 and 1.63 +/-
      0.08, respectively; all P < 0.05 compared with SCI-S). Analysis of SCI
      individuals according to injury level revealed that tetraplegic athletes had
      similar features compared with sedentary tetraplegic subjects, except for higher
      Em (10.9 +/- 0.6 vs 8.6 +/- 0.7 cm s, P < 0.05) and lower E/Em ratio (6.3 +/- 0.4
      vs 8.8 +/- 0.8, P < 0.05), whereas paraplegic athletes had similar features
      compared with sedentary paraplegic individuals, except for higher LV end
      diastolic diameter (49.4 +/- 1.4 vs 45.0 +/- 1.0 mm, P < 0.05) and Em/Am ratio
      (1.69 +/- 0.20 vs 1.19 +/- 0.08, P < 0.05) and lower LV relative wall thickness
      (0.330 +/- 0.012 vs 0.369 +/- 0.010, P < 0.05) and heart rate (67.1 +/- 4.2 vs
      81.9 +/- 2.8 bpm, P < 0.05). CONCLUSION: Regular physical activity is associated
      with improved LV diastolic function in SCI subjects and might exert distinct
      cardiac structural effects in tetraplegic and paraplegic subjects.

PMID- 24126970
TI  - The dual role of autophagy in chondrocyte responses in the pathogenesis of
      articular cartilage degeneration in osteoarthritis.
AB  - The present study aimed to analyze the responses to autophagy in osteoarthritis
      (OA) and aging chondrocytes in order to elucidate the role of autophagy in the
      pathogenesis of OA. We used multiple assays to confirm that autophagic activity
      was downregulated in chondrocytes of aged articular cartilage. Surprisingly, we
      found that the expression of autophagy-related proteins was not decreased in the
      tissues of patients with OA. We also observed that rapamycin-induced autophagy
      prevented the accumulation of subdiploid cells in young chondrocytes, while it
      induced cell death by autophagy in OA chondrocytes. Our results demonstrate that
      autophagic activity decreases with aging, and may be responsible for the
      cytoprotective effects in young cartilage. However, we found that autophagic
      activity in patients with OA was higher than in the aging group, and reported
      autophagic cell death in OA chondrocytes. These results suggest that autophagy
      plays both a cytoprotective and death-promoting role in the pathogenesis of OA. 

PMID- 24126972
TI  - Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor
      alpha and colonic mucosa interleukin-1beta, interleukin-6 levels in ulcerative
      colitis rats.
AB  - OBJECTIVE: To investigate the effects of Modified Sanhuang Decoction (, MSD)
      enema on the serum tumor necrosis factor alpha (TNF-alpha) and colonic mucosa
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6) levels in experimental
      ulcerative colitis (UC) rats. METHODS: Forty-five male Wistar rats were randomly
      divided into 4 groups: normal group (n=12), model group (n=11),
      salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was
      induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in
      the normal group and model group were clystered with 0.9% normal saline, while in
      the SASP group and MSD group were clystered with SASP and MSD enema,
      respectively. After drug administration (10 mL/kg body weight, for 7 days),
      colonic gross changes and colonic mucosa histology were observed, serum TNF-alpha
      and colonic mucosa IL-1beta, IL-6 levels were tested by enzyme linked
      immunosorbent assay and radioimmunoassay, respectively. RESULTS: As compared with
      the normal group, the experimental UC rats, the colonic mucosal damage index
      scores (CMDIs), histopathological scores (HS) and the serum TNF-alpha and colonic
      mucosa IL-1beta, IL-6 levels significantly increased (P<0.05 or P<0.01). In the
      MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared.
      The CMDIs, HS, the serum TNF-alpha and colonic mucosa IL-1beta, IL-6 levels in
      the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with
      the model group. The CMDIs in the MSD group were lower than that in the SASP
      group (P<0.05), but there were no significant differences in HS, serum TNF-alpha
      or colonic mucosa IL-1beta, IL-6 levels between the MSD and SASP groups.
      CONCLUSION: MSD enema can improve colonic mucosa impairment and decrease serum
      TNF-alpha and colonic mucosa IL-1beta, IL-6 levels in experimental UC.

PMID- 24126973
TI  - The teacher-disciple tradition and secret teaching in Chinese medicine.
AB  - The ancient teacher-disciple tradition is regarded as one of the most celebrated
      practices within the Chinese medicine world. Such traditions of secrecy, private
      wisdom and honor are deeply rooted in the theories of Confucianism. This paper
      only explores the surface of this ancient culture, by investigating relevant
      popular ancient texts and common Chinese proverbs, as well as utilizing personal
      experiences, in order to reflect on how the ancient Chinese perceived such
      practices within their own society and how secret teaching was passed on from
      teacher to student, including the revelation of secret formulas and their
      importance and how that tradition differs from our modern-day perspectives.
      Various rare manuscripts from the author's personal library are employed in order
      to provide relative examples of the importance of secret knowledge, and how these
      secrets applied in the traditional healing. 

PMID- 24126971
TI  - Fenproporex increases locomotor activity and alters energy metabolism, and mood
      stabilizers reverse these changes: a proposal for a new animal model of mania.
AB  - Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce
      mania-like behaviors in animals. In the present study, we intend to present a new
      animal model of mania. In order to prove through face, construct, and predictive
      validities, we evaluated behavioral parameters (locomotor activity, stereotypy
      activity, and fecal boli amount) and brain energy metabolism (enzymes citrate
      synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III,
      and IV of the mitochondrial respiratory chain; and creatine kinase) in rats
      submitted to acute and chronic administration of fenproporex, treated with
      lithium (Li) and valproate (VPA). The administration of Fen increased locomotor
      activity and decreased the activity of Krebs cycle enzymes, mitochondrial
      respiratory chain complexes, and creatine kinase, in most brain structures
      evaluated. In addition, treatment with mood stabilizers prevented and reversed
      this effect. Our results are consistent with the literature that demonstrates
      behavioral changes and mitochondrial dysfunction caused by psychostimulants.
      These findings suggest that chronic administration of Fen may be a potential
      animal model of mania. 

PMID- 24126974
TI  - Effect of Qingxuan Granule () on blood pressure variability of hypertensive
      patients with and without obstructive sleep apnea.
AB  - OBJECTIVE: To observe the effect of Qingxuan Granule () on blood pressure
      variability of hypertensive patients with and without obstructive sleep apnea
      (OSA). METHODS: This study was a stratified, randomized, doubled-blind, placebo
      controlled clinical trial. Ninety mild and moderate hypertensive patients with
      yin deficiency and yang hyperactivity syndrome were enrolled. Each patient
      received portable sleep monitoring for OSA diagnosis and 24-h ambulatory blood
      pressure monitoring (ABPM) for blood pressure diagnosis. According to the OSA
      diagnosis, the hypertensive patients were assigned to two subgroups, one with OSA
      (group A), the other without OSA (group B); and in each subgroup, the patients
      were randomly assigned to the treatment group (group A1 or group B1) and control
      group (group A2 or group B2). All of the patients were treated by Amlodpine
      Besylate, in addition, Qingxuan Granule was given to the treatment group (group
      A1 or group B1), and placebo was given to the control group (group A2 or group
      B2), respectively. After a 2-month treatment, each patient received portable
      sleep monitoring and 24-h ABPM again, the difference (D-value) of the blood
      pressure, and OSA index between pre-treatment and post-treatment were analyzed by
      covariance analysis in a generalized linear model. In this model, D-value was
      accepted as dependent variable Y, which was affected by treatment method
      (considered as factor a), the base level of all indices before treatment
      (considered as factor b), and OSA condition (considered as factor c). RESULTS:
      The following indices declined more in total treatment groups (groups A1+B1) than
      in total control groups (groups A2+B2, P a<0.05): 24-h systolic blood pressure
      (SBP) standard deviation (SD), daytime SBP SD, night time SBP SD, 24-h diastolic
      blood pressure (DBP) SD, 24-h DBP coefficient variation (CV), daytime DBP SD,
      night time DBP SD, and heart rate; the following indices declined less in the
      patients with OSA than those without OSA (P a<0.05): night time SBP, 24-h SBP SD,
      daytime SBP SD, night time SBP SD, 24-h DBP SD, 24-h DBP CV, daytime DBP SD,
      night time DBP SD, night time DBP CV, and heart rate; and the following indices
      increased less in the patients with OSA than those without OSA (P b<0.05): night
      time SBP fall rate, night time DBP fall rate. No significant difference was found
      in OSA' indices after taking Qingxuan Granule (P>0.05), with the exception that
      hypopnea index decreased and hypopnea improved (P<0.05). CONCLUSIONS: For
      hypertensive patients, Qingxuan Granule could improve the blood pressure
      variability, and this effect could be weakened by OSA; also Qingxuan Granule
      could improve hypopnea in OSA patients.

PMID- 24126977
TI  - Meta-analysis of oral Chinese herbal medicine as an adjuvant treatment in
      relieving pain secondary to bone metastases.
AB  - OBJECTIVE: To assess the effectiveness of oral Chinese herbal medicine (CHM) in
      relieving pain secondary to bone metastases in patients. METHODS: The searched
      electronic literature databases included both English and Chinese articles
      published in the MEDLINE, EMBASE, Wanfang database and China National Knowledge
      Infrastructure (up to December 2012). The studies included randomized controlled
      trials (RCTs) comparing CHM plus conventional treatment with conventional
      treatment alone for patients with pain secondary to bone metastases. The outcomes
      were the odds ratio (OR) with 95% confidence intervals (CI) for the pain-relief
      rate and adverse events. RESULTS: A total of 16 RCTs involving 1,008 patients
      were identified and analyzed. All of the included RCTs were associated with a
      moderate to high risk of bias. In the metaanalysis, CHM plus conventional
      treatment increased the pain-relief rate compared with the conventional treatment
      alone (OR, 2.59; 95% CI 1.95 to 3.45). In subgroup analysis, the pooled OR of the
      pain-relief rate of CHM plus conventional treatment compared with conventional
      treatment was 3.11 (95% CI 2.01 to 4.79) for CHM plus bisphosphonates, 2.24 (95%
      CI 1.33 to 3.78) for CHM plus analgesics, 2.28 (95% CI 1.09 to 4.79) for CHM plus
      radiotherapy, and 2.22 (95% CI 0.95 to 5.15) for CHM plus analgesics and
      bisphosphonates. The adverse events included nausea, vomiting, dizziness, fever,
      and constipation. No serious adverse events were reported in any of the included
      studies. CONCLUSIONS: CHM interventions appear to have beneficial effects on pain
      secondary to bone metastases in patients. However, published efficacy trials are
      small in size to draw any firm conclusions.

PMID- 24126975
TI  - Anti-inflammatory and Antimicrobial Effects of Anthocyanin Extracted from Black
      Soybean on Chronic Bacterial Prostatitis Rat Model.
AB  - OBJECTIVE: To investigated the anti-inflammatory and antimicrobial effects of
      anthocyanins extracted from black soybean on the chronic bacterial prostatitis
      (CBP) rat model. METHODS: The Sprague-Dawley rats were divided into 4 groups,
      including control, ciprofloxacin, anthocyanins and anthocyanins with
      ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial
      suspension (Escherichia coli Z17 O2:K1:H-) into Sprague-Dawley rats was conducted
      to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and
      histological analysis on the prostate were analyzed for each group. RESULTS: The
      use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed
      statistically significant decreases in bacterial growth and improvements in the
      reduction of prostatic inflammation compared with the control group (P<0.05). The
      anthocyanins with ciprofloxacin group showed a statistically significant decrease
      in bacterial growth and improvement in prostatic inflammation compared with the
      ciprofloxacin group (P<0.05). CONCLUSIONS: These results suggest that
      anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a
      synergistic effect with ciprofloxacin. Therefore, we suggest that the combination
      of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a
      higher rate of treatment success.

PMID- 24126976
TI  - The role of Chinese medicine in clinical oncology.
AB  - Chinese Medicine (CM) has been used for several thousand years, playing an
      important role in the prevention and treatment of diseases including cancer. In
      the recent four decades, a number of CM herbs have aroused extreme interest in
      the world-isolating anticancer components from medicinal herbs, using them as
      biological response modifiers, and most recently as angiogenesis inhibitors. The
      present review reports both the experimental and clinical results obtained in the
      field of clinical oncology, especially conducted by our group. The review also
      presents the possible future of integration of CM and modern medicine in basic
      research and clinical practice, especially when CM used as adjuvant and
      maintenance therapy. 

PMID- 24126979
TI  - Research Activities and Perceptions of Barriers to Research Utilization Among
      Turkish Nurses.

PMID- 24126978
TI  - Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer
      cells in vitro.
AB  - Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer
      in women and is the leading cause of cancer-related mortality among women. It is
      extremely rare but highly lethal in men. The deubiquitinating enzyme USP39 plays
      important roles in mRNA processing, and our previous data showed that high levels
      of USP39 are selectively present in different types of human breast tumor cells.
      The potential of USP39 as a therapeutic target for breast cancer was
      investigated. The expression levels of USP39 protein in 23 breast cancer
      specimens were quantified using an immunohistochemical assay and were found to
      have high levels in human breast cancer tissues when compared to these levels in
      normal breast tissues. In the breast cancer cell line MCF-7, USP39 expression was
      knocked down by a lentiviral short hairpin RNA (shRNA) delivery system. The RNA
      interference (RNAi)-mediated downregulation of USP39 expression markedly reduced
      the proliferative and colony forming ability of MCF-7 cells. In addition, the
      inhibition of USP39 induced G0/G1-phase arrest and apoptosis of the cells. These
      results suggest that USP39 may act as an oncogenic factor in breast cancer and
      could be a potential molecular target for breast cancer gene therapy. 

PMID- 24126980
TI  - Pediatric polysomnography for sleep-disordered breathing prior to tonsillectomy:
      a guideline review.
AB  - Snoring and other signs of sleep-disordered breathing (SDB) represent a common
      management challenge for the pediatrician, pulmonologist, anesthesiologist, and
      otolaryngologist. In 2011, the American Academy of Otolaryngology-Head and Neck
      Surgery published a clinical practice guideline for the treatment of patients
      with SDB. This guideline provides indications for polysomnography use in patients
      with SDB. In this article, we discuss the management of SDB in pediatric
      patients, which relies on the accurate assessment of symptoms of SDB,
      identification of comorbidities known to increase the severity of SDB, and
      appropriate preoperative assessment of the patient.

PMID- 24126981
TI  - Childhood obstructive sleep apnea syndrome: a review of the 2012 American Academy
      of Pediatrics guidelines.
AB  - On a busy day at the pediatric office, child health care practitioners may see
      children of different ages present with symptoms such as inattentiveness,
      hyperactivity, aggression, behavioral problems, excessive sleepiness, difficulty
      waking up in the morning, learning problems, frequent awakening at night,
      restless sleep, morning headaches, and nocturnal enuresis. Children with these
      symptoms may be underweight or morbidly obese; healthy; or suffering from asthma,
      seasonal allergies, or other ailments. What they will likely have in common is a
      fairly well-known and yet under-recognized condition - obstructive sleep apnea
      syndrome (OSA). The American Academy of Pediatrics first published "Clinical
      Practice Guideline: Diagnosis and Management of Childhood Obstructive Sleep Apnea
      Syndrome" in 2002. However, with the increase in obstructive sleep apnea syndrome
      research, they revised these guidelines in 2012. These new guidelines evaluate
      obstructive sleep apnea syndrome diagnostic techniques, describe available
      treatment options, and provide follow-up recommendations. This article explores
      those revisions.

PMID- 24126982
TI  - Prader-Willi syndrome and sleep-disordered breathing.
AB  - Prader-Willi Syndrome is a complex neurogenetic disorder characterized by
      appetite dysregulation, obesity with decreased muscle mass and increased fat
      mass, behavioral problems, various endocrinopathies, and sleep and respiratory
      abnormalities. Respiratory issues include both central and obstructive sleep
      apnea, excessive daytime sleepiness, narcolepsy, and impaired ventilatory
      control. There is some controversy as to whether growth hormone treatment, which
      is the standard of care for patients with Prader-Willi Syndrome, exacerbates or
      ameliorates the sleep-disordered breathing issues associated with this syndrome.
      The natural history of sleep and breathing issues and the issues surrounding
      growth hormone treatment on sleep-disordered breathing are discussed.

PMID- 24126983
TI  - Pediatric obesity, metabolic syndrome, and obstructive sleep apnea syndrome.
AB  - The prevalence of obesity in the pediatric population has dramatically increased
      in the last 30 years. While the adverse health effects of obesity have long been
      recognized in adults, many of these complications are now understood to begin in
      early childhood. Obese children and adolescents are significantly more likely
      than their peers of healthy weight to suffer from obstructive sleep apnea and
      metabolic syndrome. In turn, affected individuals may experience myriad serious
      clinical sequelae; neuro-cognitive, psychiatric, cardiovascular, and
      endocrinologic complications have each been extensively documented. Thus, the
      spectrum of obesity-related disease represents a serious but preventable threat
      to personal and family wellness; additionally, it is a source of considerable
      health care expenditure and represents a national and international health
      crisis. The optimal care of these patients will be best achieved through the
      pediatric health care provider's timely recognition of these clinical problems
      and knowledge of appropriate intervention strategies.

PMID- 24126984
TI  - Just a scary dream? A brief review of sleep terrors, nightmares, and rapid eye
      movement sleep behavior disorder.
AB  - The clinical spectrum of sleep disorders in children is broad, ranging from
      primary snoring and obstructive sleep apnea (OSA) syndrome to complex sleep
      related behaviors and movement disorders. Although snoring and OSA typically
      receive significant attention and discussion, other biologically based sleep
      disorders are as common, if not more common, in children. A general pediatrician
      is frequently presented with the complaint of sleep talking, sleep walking, or
      abnormal movements during sleep. Even more alarming is the presentation of the
      child suddenly and explosively screaming during sleep. Such complaints fall under
      the category of parasomnias. Exclusive to sleep and wake-to-sleep transitions,
      these parasomnias include arousals with abnormal motor, behavioral, autonomic, or
      sensory symptoms. Parasomnias can be noticeably dissimilar in clinical
      manifestations, but most share biologic characteristics. Three parasomnias
      associated with loud vocalizations associated with sleep that can present to
      general practitioners include sleep terrors, nightmares, and rapid eye movement
      sleep behavior disorder (RBD). Although usually benign, these sleep disorders can
      be disruptive and even potentially dangerous to the patient and can often be
      threatening to quality of life. In this article, we describe the clinical
      features of some of these disorders and how to differentiate between their
      alarming presentations.

PMID- 24126985
TI  - A sleepy topic.

PMID- 24126987
TI  - Reimbursement for primary care mental health.

PMID- 24126988
TI  - A 4-year-old boy with a yellow bump on his knee.

PMID- 24126989
TI  - Taking a 'PASS' on alternative immunization schedules.

PMID- 24126990
TI  - A 14-year old boy with sore throat and syncope.

PMID- 24126991
TI  - Sleep disorders in children.

PMID- 24126992
TI  - Acne in childhood: an update.

PMID- 24126994
TI  - A conversation with Robert Listernick, MD. Interview by Stanford T. Shulman.

PMID- 24126996
TI  - [Field trial on the simultaneous vaccination against porcine circovirus type 2
      (PCV2) and Mycoplasma hyopneumoniae].
AB  - OBJECTIVE: The objective of the present study was to investigate whether a
      combined or concurrent application of two vaccines against Mycoplasma
      hyopneumoniae (M. hyo.) and porcine circovirus type 2 (PCV2) in suckling piglets
      can be as effective as the single use of both products. MATERIAL AND METHODS: A
      total of 598 piglets were allocated to five groups. In the 1st and 3rd weeks of
      life the placebo Porcilis(r) Diluvac forte and the two vaccines Porcilis(r) M HYO
      ("M HYO") and Porcilis(r) PCV ("PCV") were administered according to the
      following scheme: group A: placebo/PCV; group B: M HYO/M HYO; group C:
      placebo/placebo; group D: M HYO/M HYO + PCV (combined single dose); group E:
      placebo/M HYO + PCV (different injection sites). Lung lesions due to M. hyo.
      infection were recorded at slaughter, and average daily weight gain, morbidity,
      mortality, serum PCV2 load and specific humoral immune responses were compared
      between the groups. Local and systemic side effects were recorded. RESULTS:
      Sporadic impairment of the herd health status due to piglet diarrhoea (n = 111)
      from the 1st to 3rd weeks of life were not associated with M. hyo. or PCV2. A
      tendency towards a higher average daily weight gain was found in vaccinated pigs
      compared to the control group. Slight differences between groups in terms of lung
      lesions, morbidity and mortality were not significant. M. hyo. and PCV2 antibody
      titers were significantly higher in vaccinated than in non-vaccinated pigs. One
      pig from both group A (PCV2) and group C (placebo) displayed local reactions at
      the vaccination site. CONCLUSION AND CLINICAL RELEVANCE: A positive effect on
      animal health can be achieved by vaccination against M. hyo. and PCV2 in herds
      with suboptimal health status. A simultaneous vaccination either by a combined or
      concurrent application has no negative effect on health status. Simultaneous
      vaccination yielded the same positive effect on average daily weight gain as
      single vaccinations. Therefore, a simultaneous vaccination against M. hyo. and
      PCV2, which reduces workload and is beneficial for animal welfare, can be
      recommended.

PMID- 24126997
TI  - Relation between intravascular electrolyte level and course of parturition in
      dairy cows.
AB  - OBJECTIVE: To determine the intravascular electrolyte status in dairy cows with
      respect to age and different courses of parturition to clarify etiological
      factors influencing peri- or intrapartal imbalances of electrolyte homeostasis.
      MATERIAL AND METHODS: A total of 64 cows at birth were evaluated (primiparous n =
      34, pluriparous n = 30). Thirty-three cows showed normal delivery, while 31 cows
      had a complicated birth. Blood samples were collected intra partum (i. p.) and 2,
      4, 6, 8, 12, 16, 24 h post partum (p. p.) as well as [2, 3, 4, 5, 7, 10 days p.
      p. and levels of total calcium (Catotal), ionized calcium (Caion), inorganic
      phosphate (Pa), Mg, Na, K, Cl were determined. RESULTS: The results revealed that
      electrolytes show great fluctuation during and immediately p. p. in relation to
      age. Already during parturition pluriparous cows had a lower Catotal and Pa
      concentration compared to primiparous animals. Cows with dystocia exhibited a
      more intensive and longer lasting decrease of Ca compared to cows with normal
      birth. In relation to age and severity of birth Pa concentration showed a
      differing but basically typical course for this electrolyte. Mg, Na, K and Cl
      concentrations were higher during and immediately after birth compared to p. p.
      values. Until day 10 p. p. these electrolyte concentrations declined more in
      older cows with dystocia compared to younger animals. However, the influence of
      dystocia on concentration of these electrolytes was milder in contrast to Ca and
      Pa. CONCLUSIONS: In summary, primarily older cows are predisposed to imbalances
      of electrolyte homeostasis intra partum and at the beginning of the lactation.
      These changes are potentiated in case of complications during parturition.
      Intravascular Catotal, Caion as well as Pa are most severely affected. CLINICAL
      RELEVANCE: These results may constitute the basis for a comprehensive
      metaphylaxis during the peripartal period, especially in cows after dystocia, to
      positively influence the early convalescence phase.

PMID- 24126998
TI  - Establishment of a practical sperm penetration test for bovine semen.
AB  - OBJECTIVE: Several methods for evaluating semen quality have been developed in
      addition to traditional semen analysis. Most of these methods are very complex
      and require expensive technical equipment as well as special knowledge to be
      performed. The aim of this study was to establish an easy and cost-effective
      sperm penetration test for bovine semen using artificial media. Additionally a
      standard procedure for test performance should be figured out. MATERIAL AND
      METHODS: In the first part of the study four different capillary tubes or
      pipettes were evaluated in order to determine the most appropriate one to use in
      the penetration test. In the second part of the study the tubes were filled with
      different compositions of polyacrylamide gel and subsequently incubated at 37.5 
      degrees C for 30 minutes. Sperm penetration was then evaluated using a phase
      contrast microscope, measuring the penetration distance of the first, the first
      motile and the five vanguard motile spermatozoa as well as determining the number
      of sperm cells cumulated per low power field (LPF) at three distinct distances in
      the tube. RESULTS: Non-heparinised haematocrit capillary tubes were the most
      appropriate tubes for performance of sperm penetration test as 100% of used
      capillaries were evaluable after incubation and size of the capillaries allowed a
      simple handling and good visualisation of migrated spermatozoa. Best results were
      achieved with 1.9% polyacrylamide gel containing phosphate-buffered saline.
      Measuring the penetration distance of the vanguard motile sperm cell can be
      recommended for test evaluation. CONCLUSION: A sperm penetration test with 1.9%
      polyacrylamide using non-heparinised capillary tubes was established. Results
      showed high reproducibility, the procedure is simple to carry out and only
      requires a phase contrast microscope.

PMID- 24126999
TI  - [Comparison of different electrocardiographic techniques for the detection of
      arrhythmias in horses].
AB  - OBJECTIVE: The aim of the study was to extend the range of the
      electrocardiographic examination in horses, evaluating the practicability of
      special electrocardiographic techniques (exercise- and Holter-ECG) and comparing
      these with more common techniques (resting-ECG) in equine medicine. MATERIAL AND
      METHODS: Electrocardiographic examination (resting-ECG for 1 minute, exercise-ECG
      and Holter-ECG) was performed in 20 horses without any clinical or
      echocardiographic findings and in 80 patients with abnormal findings (valvular
      regurgitation and/or atrial fibrillation). RESULTS: In comparison with the
      resting-ECG, the exercise-ECG demonstrated more atrial and ventricular premature
      beats, while the Holter-ECG had a higher detection rate of 2nd degree
      atrioventricular or sinuatrial blocks, and of ventricular and atrial premature
      depolarisations (p < 0.001). In comparison to the exercise-ECG, the Holter-ECG
      registered more 2nd degree atrioventricular blocks (p < 0.001) and ventricular (p
      < 0.001) or atrial premature contractions (p < 0.01). Atrial fibrillation was
      detected in every recorded ECG-type, but Holter-ECG provided additional
      information. Three of 16 horses with atrial fibrillation had R-on-T-episodes
      during Holter-monitoring. In addition to more common findings in the ECG, Holter
      monitoring detected a 2nd degree atrioventricular block associated with an
      adjacent ventricular escape beat in a horse without any clinical or
      echocardiographic findings. An accelerated idioventricular rhythm was identified
      in a horse without any clinical or echocardiographic findings and in a horse with
      mitral valve insufficiency. CONCLUSION AND CLINICAL RELEVANCE: The Holter-ECG is
      a useful tool in the evaluation of heart disease and could supply additional
      information when compared to the usual diagnostic electrocardiographic procedures
      used in horses. Exercise-ECG should not be replaced by Holter-ECG, however,
      Holter-EGC can provide additional diagnostic value.

PMID- 24127000
TI  - [Significance of the dry period for the development and prevention of new
      infections of the bovine mammary gland].
AB  - The dry period poses an extraordinarily high risk of new infections for the
      bovine mammary gland. Environmental pathogens are of particular importance during
      this time. Normally, an infection during the dry period does not cause clinical
      symptoms, but is often responsible for clinical mastitis in the first weeks of
      lactation. Reducing new infections in dry cows can significantly decrease
      mastitis incidence in early lactation. During the course of the dry period, the
      new infection rate does not remain constant, but peaks immediately after drying
      off and shortly before calving. The chance of a new infection is influenced
      multifactorially by the animal, pathogen and environment. In this context, the
      closure of the teat canal using a keratin plug is very important. There are
      different approaches to antibiotic dry cow treatment. Either all udder quarters
      of all dry cows are treated (blanket dry-cow treatment) or just the udder of
      animals with a proven infection or an increased somatic cell count (selective dry
      cow treatment). In the latter case, all udder quarters of an animal may be
      treated or just the one in which the infection or the increased somatic cell
      count was found. Instead of, or as a supplement to antibiotic treatment, teat
      sealers can be used. They support or take over the function of the keratin plug
      by closing the teat canal. In addition, there are some alternative methods to
      prevent new infections. Nevertheless, reducing the risk of infection is of
      primary importance. For this purpose, there are numerous options for improving
      hygiene in the environment of dry cows. 

PMID- 24127001
TI  - [Tenesmus and stranguria in a heifer caused by a urachal cyst in the bladder
      wall].
AB  - A 10-month-old Brown Swiss heifer was referred to our clinic be- cause of
      pollakiuria, stranguria and tenesmus. Ultrasonography and endoscopy revealed a
      cyst-like lesion at the apex of the urinary bladder. The apex of the bladder was
      surgically removed with the patient in dorsal recumbency under general
      anaesthesia. Histological examination revealed a cyst lined with urothelium in
      the wall of the urinary bladder. The heifer was discharged 9 days after surgery.
      According to the owner's information the animal did not show any clinical signs 6
      months later. 

PMID- 24127003
TI  - What did I know?

PMID- 24127002
TI  - The multivariate egg: quantifying within- and among-clutch correlations between
      maternally derived yolk immunoglobulins and yolk androgens using multivariate
      mixed models.
AB  - Egg components are important mediators of prenatal maternal effects in birds and
      other oviparous species. Because different egg components can have opposite
      effects on offspring phenotype, selection is expected to favour their mutual
      adjustment, resulting in a significant covariation between egg components within
      and/or among clutches. Here we tested for such correlations between maternally
      derived yolk immunoglobulins and yolk androgens in great tit (Parus major) eggs
      using a multivariate mixed-model approach. We found no association between yolk
      immunoglobulins and yolk androgens within clutches, indicating that within
      clutches the two egg components are deposited independently. Across clutches,
      however, there was a significant negative relationship between yolk
      immunoglobulins and yolk androgens, suggesting that selection has co-adjusted
      their deposition. Furthermore, an experimental manipulation of ectoparasite load
      affected patterns of covariance among egg components. Yolk immunoglobulins are
      known to play an important role in nestling immune defence shortly after
      hatching, whereas yolk androgens, although having growth-enhancing effects under
      many environmental conditions, can be immunosuppressive. We therefore speculate
      that variation in the risk of parasitism may play an important role in shaping
      optimal egg composition and may lead to the observed pattern of yolk
      immunoglobulin and yolk androgen deposition across clutches. More generally, our
      case study exemplifies how multivariate mixed-model methodology presents a
      flexible tool to not only quantify, but also test patterns of (co)variation
      across different organisational levels and environments, allowing for powerful
      hypothesis testing in ecophysiology. 

PMID- 24127004
TI  - The density difference between tissue and neural probes is a key factor for glial
      scarring.
AB  - A key to successful chronic neural interfacing is to achieve minimal glial
      scarring surrounding the implants, as the astrocytes and microglia may
      functionally insulate the interface. A possible explanation for the development
      of these reactions is mechanical forces arising between the implants and the
      brain. Here, we show that the difference between the density of neural probes and
      that of the tissue, and the resulting inertial forces, are key factors for the
      development of the glial scar. Two probes of similar size, shape, surface
      structure and elastic modulus but differing greatly in density were implanted
      into the rat brain. After six weeks, significantly lower astrocytic and
      microglial reactions were found surrounding the low-density probes, approaching
      no reaction at all. This provides a major key to design fully biocompatible
      neural interfaces and a new platform for in vivo assays of tissue reactions to
      probes with differing materials, surface structures, and shapes. 

PMID- 24127005
TI  - Brain-derived neurotrophic factor expression in dorsal root ganglia of a lumbar
      spinal stenosis model in rats.
AB  - This study aimed to investigate the expression of brain-derived neurotrophic
      factor (BDNF) in dorsal root ganglia (DRG) of a rat model of lumbar spinal
      stenosis (LSS). Adult male rats were divided into the operation and sham
      operation groups. The operation group was comprised of the rat models of LSS.
      Walking distance and BDNF expression levels in DRG were measured in the two
      groups at different time points. The total BDNF protein levels and positive cell
      mean optical density (MOD) values in the operation group were significantly
      higher at each time point compared with that of the sham operation and
      preoperative control groups (P<0.05). The total BDNF protein levels and MOD
      values following sport in the operation group were significantly higher compared
      with those prior to sport (P<0.05). In the sham operation group, BDNF protein
      levels and MOD values before and after sport at each time point showed no
      significant differences than those of the operation group (P>0.05). Moreover,
      BDNF protein levels and MOD values in the operation group indicated a negative
      correlation with walking distance. The present study demonstrated that the
      expression of BDNF in rat models of LSS increased with time and was associated
      with a decrease in walking distance. BDNF was therefore important for the process
      of intermittent claudication caused by LSS.

PMID- 24127006
TI  - Diagnosis and management of Down syndrome.
AB  - Down syndrome is the commonest chromosomal disorder causing mild to moderate
      intellectual disability, yet it is one of the neglected disorder amongst
      practicing physicians. Children with Down syndrome when intervened early by
      speech therapy, physiotherapy and occupational therapy and given proper medical
      attention for different health issues, can have a better long term outcome as
      compared to other genetic causes of intellectual disability. This paper would
      help the general practitioners to identify children with Down syndrome and to
      manage the common problems associated with this condition. 

PMID- 24127007
TI  - A novel frameshift mutation in TWIST2 gene causing Setleis syndrome.
AB  - The authors report on a child with Setleis syndrome (OMIM 227260). She is born to
      a consanguineous couple with bitemporal scar like defects resembling forceps
      marks. She had other classical features resembling autosomal recessive Setleis
      syndrome. The authors identified a novel homozygous deletion of a single
      nucleotide (c.91delC) in TWIST2 gene leading to the premature truncation of
      protein (p.R31GfsX71). Umbilical hernia and genital anomalies are being reported
      for the first time with this condition. This is the fourth mutation proven family
      of Setleis syndrome. 

PMID- 24127008
TI  - Comparison of non verbal learning difficulties in preschoolers born preterm with
      the term born peers.
AB  - OBJECTIVES: To identify the incidence and pattern of specific areas of non verbal
      learning deficits (NVLD) associated with preterm and term born peers and also to
      evaluate influence of gestational age on cognition, motor, language and behavior
      in preterm and term infants. METHODS: Children were screened for prematurity by
      giving parents a comprehensive questionnaire covering the family details, birth
      history, medical history and school performance. After finding their suitability,
      the children were picked randomly using the lottery method. Hundred children born
      moderately preterm were allocated in Group B and 100 term born children were
      recruited in Group A. Participants of both the groups were evaluated using the
      First STEP- screening test to evaluate preschoolers. RESULTS: This study revealed
      that there was significant difference between both the preterm and the control
      group in all the domains of First STEP and there was 10 % incidence of NVLD in
      preterm born preschoolers. CONCLUSIONS: Thus, the gestational age influences the
      cognitive, motor, behavior and academic performance in the preschoolers, thereby
      increasing the incidence of NVLD in preterm than the term born peers.

PMID- 24127010
TI  - A novel cancer therapeutic using thrombospondin 1 in dendritic cells.
AB  - Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor
      growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in
      dendritic cells (DCs) influences tumor progression. We investigated tumor growth
      and immune mechanism by downregulation of TSP-1 in dendritic cells.
      Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced
      anticancer therapeutic effects. Tumor-infiltrating CD4(+) and CD8(+) T cells were
      increased after the administration of TSP-1 shRNA. The expression of interleukin
      12 and interferon-gamma in the lymph nodes was enhanced by injection of TSP-1
      shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the
      tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of
      CD8(+) T cells. Injection of CD11c(+) TSP-1-knockout (TSP-1-KO) bone marrow
      derived DCs (BMDCs) delayed tumor growth in tumor-bearing mice. Similarly,
      antitumor activity induced by TSP-1-KO BMDCs was abrogated by depletion of CD8(+)
      T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP
      family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1
      shRNA functioned as an immunotherapeutic adjuvant to augment the therapeutic
      efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs
      produces an effective antitumor response that is opposite to the protumor effects
      by silencing of TSP-1 within tumor cells. 

PMID- 24127011
TI  - Age impacts the pattern of care for elderly patients with rectal cancer.
AB  - PURPOSE: This study analyzed the current approaches for rectal cancer treatment
      in elderly patients. METHODS: We retrospectively studied 240 rectal cancer
      patients who had undergone radiotherapy from 2000 to 2008. The ages of the
      patients ranged from 65 and 75 years (group A, n = 127) and older than 75 years
      (group B, n = 113). The distribution of the Charlson comorbidity index was
      similar between the two groups, but the ECOG performance status (PS) differed
      between the groups (66 % of the patients of group A were PS 0, and 40 % were PS 0
      in group B (p < 0.0001)). The tumor stages were comparable between groups.
      RESULTS: The median age of the patients was 74.3 years (range 65-90.6). Treatment
      was discussed during a multidisciplinary cancer team meeting before treatment for
      55 % of the cases in group A and 73 % of the cases in group B (p < 0.001), and
      treatment proposals were in accordance with guidelines in 96 % of the cases in
      group A and 76 % of the cases in group B (p < 0.001). Group B patients received
      slightly less concurrent chemotherapy (35 vs. 30 % for group A; p = 0.54), more
      hypofractionated radiotherapy (41 vs. 54 % for group A; p = 0.064), less surgery
      (92 vs. 80 % for group A; p = 0.014), and less adjuvant chemotherapy (34 vs. 10 %
      for group A; p < 0.001). Finally, 80 % of the patients in group A and 60 % of the
      patients in group B received treatment in accordance with guidelines (p = 0.007)
      and in the logistic regression model. Non-metastatic patients who were aged below
      75 years were predicted for conformal management (HR = 0.323; 95 % CI = 0.152
      0.684) irrespective of their performance status, comorbidity, or disease stage.
      CONCLUSIONS: Treatment proposals and administered therapy differed according to
      age.

PMID- 24127012
TI  - Synergistic effect of EMS1-shRNA and sorafenib on proliferation, migration,
      invasion and endocytosis of SMMC-7721.
AB  - To investigate the synergistic effect of EMS1-PSilencer4.1-shRNA (EMS1-shRNA) and
      sorafenib on biological behaviors of HCC cell line SMMC-7721. EMS1-shRNA was
      constructed and transfected into SMMC-7721 cells. Decreased levels of
      EMS1/cortactin were tested in RT-QPCR and Western blot assay. Proliferation,
      migration, invasion, and endocytosis of SMMC-7721 were tested through CCK8 assay,
      scratch test, transwell invasion assay and transferrin endocytosis assay,
      respectively. Raf-1 was detected by Western blot assay. HCC xenograft model was
      prepared to observe tumor growth. Animals were euthanized and their subcutaneous
      lesions were weighed. Then the tissues were fixed and paraffin sections were
      prepared. Cortactin and PCNA (a proliferation marker) were then detected by
      immunohistochemistry. As compared with untreated group, the levels of EMS1 gene
      and cortactin protein in EMS1-shRNA-transfected group were significantly reduced;
      Among EMS1-shRNA-transfected group, sorafenib-treated group and combined group,
      the levels of proliferation at 48 h were reduced to 83.69, 57.18, 41.94 %; the
      levels of migration were reduced to 49.69, 60.83, and 21. 67 %; the levels of
      invasion were reduced to 42.97, 53.65, 18.18 %; the levels of endocytosis were
      reduced to 37.15, 97.95 % (p > 0.05), 20.68 % (p < 0.05, respectively). Western
      blot assay showed levels of Raf-1 were reduced to 68.56, 59.09, 21.90 %. The
      tumor volume and weight of nude mice HCC xenograft tumors were reduced
      significantly either (p < 0.05, respectively). Immunohistochemistry showed levels
      of cortactin and PCNA were reduced to 35.69, 93.84, 23.68 and 87.69, 43.84, 33.68
      % in each group, respectively. The biological behaviors of SMMC-7721 were
      inhibited in the presence of EMS1-shRNA and sorafenib both alone and in
      combination. The combination of the agents improved the curative effect over
      either single agent, showing synergetic effect.

PMID- 24127013
TI  - The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone
      sarcomas (Review).
AB  - Bone sarcomas, which comprise less than 1% of all human malignancies, are a group
      of relatively rare mesenchymal-derived tumors. They are mainly composed of
      osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in
      adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to
      the high propensity for lung metastasis, which is the leading cause of mortality
      in patients with bone sarcomas. Chemokines are a superfamily of small pro
      inflammatory chemoattractant cytokines which can bind to specific G protein
      coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also
      designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its
      cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7),
      with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the
      activation of several downstream signaling pathways that regulate tumor
      progression and metastasis. In this review, the structure and function of CXCL12
      and its receptors, CXCR4 and CXCR7, as well as many factors affecting their
      expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated
      protein kinase (MAPK) pathways are the two most important downstream pathways
      regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone
      sarcomas, including tumor cells and samples and the correlation between
      CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also
      discussed. In addition, we review the involvement of the CXCL12-CXCR4/CXCR7 axis
      in the growth and metastasis of bone sarcomas and the targeting of this axis in
      preclinical studies. 

PMID- 24127014
TI  - [Squamous cell carcinoma developing in oral lichen planus].
AB  - Oral lichen planus is a mucosal inflammatory disease whose pathogenesis is
      unclear. The chronic inflammation leads to development of a squamous cell
      carcinoma in 1-2% of the patients; we present an exemplary case. 

PMID- 24127015
TI  - Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under
      recognized condition.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life
      threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs
      include prolonged fever, organomegaly, and persistent unexplained cytopenias. In
      spite of the well known diagnostic criteria put forth by HLH society, this
      continues to pose great diagnostic challenge in both pediatric and adult
      intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29,
      40, and 17 years) and 3 pediatric (2 males, 1 female, aged 1 month, 6 months, and
      12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic
      criteria. Definite evidence of hemophagocytosis was noted in 4 patients on
      initial bone marrow examination. The underlying etiologies were as follows:
      Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset
      juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous
      snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and
      Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was
      presumed to have been exacerbated by administration of granulocyte monocyte
      colony stimulating factor (GMCSF) for severe neutropenia. Two patients died with
      disseminated intravascular coagulation (DIC) and multi organ failure within few
      days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and
      etoposide was started in one patient only. Due to lack of specificity of
      diagnostic criteria, diagnosing and differentiating HLH from its closest
      mimickers like sepsis/septic shock may be quite challenging in critically ill
      patients. Therefore, increasing awareness among physicians is essential for early
      diagnosis and effective therapy to reduce the mortality. 

PMID- 24127016
TI  - In utero magnetic resonance imaging for diagnosis of dural venous sinus ectasia
      with thrombosis in the fetus.
AB  - BACKGROUND: Dural venous sinus ectasia with thrombosis (DVSET) in the fetus is a
      rare condition that can be diagnosed prenatally with the use of fetal MR imaging,
      yet with limited indication of long-term clinical significance. OBJECTIVE: To
      describe and evaluate the diagnostic value of fetal MR imaging in the prenatal
      diagnosis of dural venous sinus ectasia with thrombosis and its clinical
      significance. MATERIALS AND METHODS: We report a series of nine fetuses with
      dural venous sinus ectasia with thrombosis. The mothers, located in four feto
      maternal centres, were referred for fetal MR imaging due to space occupying
      lesions identified on second-trimester antenatal ultrasound. RESULTS: In all but
      one case the dural venous sinus ectasia with thrombosis was in the vicinity of
      the venous confluence (VC) with various extension in the posterior dural sinuses.
      Antenatal follow-up imaging was performed in seven cases and showed progression
      in one, stable appearances in one and regression in five cases. Three pregnancies
      were terminated. In the remaining six cases there was no reported neurological
      deficit at up to 44 months of clinical follow-up. CONCLUSION: This is among the
      largest series of postnatal clinical follow-up in cases of prenatal diagnosis of
      dural venous sinus ectasia with thrombosis in the literature. Clinical follow-up
      suggests a good prognosis when antenatal follow-up shows partial or complete
      thrombus resolution.

PMID- 24127017
TI  - Molecular crowding-facilitated synthesis of DNA-templated Ag nanoclusters with
      enhanced fluorescence emission and quantum yield.
AB  - Molecular crowding was found to significantly facilitate synthesis of DNA
      templated Ag nanoclusters, which offered an effective and general strategy for
      preparation of Ag nanoclusters with improved fluorescence emission and quantum
      yield. 

PMID- 24127018
TI  - Strain effects on oxygen transport in tetragonal zirconium dioxide.
AB  - Temperature accelerated dynamics and molecular dynamics simulations are used to
      investigate the strain effects on oxygen interstitial and vacancy migration in
      tetragonal zirconium dioxide. At zero external strain, the anisotropic migration
      mechanisms of oxygen defects are characterized. At non-zero strains, both the
      crystal structure and defect migration barriers are modified by strain. Under
      compressive strains, the defect migration barrier increases with the increasing
      strain for both interstitials and vacancies. The crystal structure transforms
      from a tetragonal to a nearly cubic fluorite structure. Accordingly, the defect
      migration becomes nearly isotropic. Under dilative strains, the migration barrier
      first decreases then increases with increasing strain for both types of defects.
      The tetragonal phase transforms to a lower symmetry structure that is close to
      the orthorhombic phase. In turn, the defect migration becomes highly anisotropic.
      Under both compressive and dilative strains, interstitials respond to strain more
      strongly than vacancies. At small dilative strains, an oxygen interstitial has
      comparable diffusivity to a vacancy, suggesting that both types of defects can
      contribute to oxygen transport, if they are present. Although currently no
      previous result is available to validate oxygen interstitial diffusion behavior,
      the trend of strain effects on oxygen vacancy diffusion is in good agreement with
      available experimental and theoretical studies in the literature. 

PMID- 24127019
TI  - Incidence and clinical impact of respiratory viruses in adults with cystic
      fibrosis.
AB  - BACKGROUND: Viral respiratory infection (VRI) is a common cause of pulmonary
      exacerbations in children with cystic fibrosis (CF). The importance of VRI in
      adult CF populations is unclear. OBJECTIVE: To determine the incidence and
      clinical impact of VRI among adults with CF. METHODS: One hundred adults with CF
      were followed up prospectively for 12 months. Sputum, nose swabs and throat swabs
      were collected every 2 months and at onset of pulmonary exacerbation. PCR assays
      for adenovirus, influenza A&B, human metapneumovirus, parainfluenza 1-3,
      respiratory syncytial virus and human rhinovirus were performed on each sample.
      Symptom scores, spirometry and inflammatory markers were measured at each visit.
      RESULTS: One or more respiratory viruses were detected in 191/626 (30.5%) visits.
      Human rhinovirus accounted for 72.5% of viruses. Overall incidence of VRI was
      1.66 (95% CI 1.39 to 1.92) cases/patient-year. VRI was associated with increased
      risk of pulmonary exacerbation (OR=2.19; 95% CI 1.56 to 3.08; p<0.001) and
      prescription of antibiotics (OR=2.26; 95% CI 1.63 to 3.13; p<0.001). Virus
      positive visits were associated with higher respiratory symptom scores and
      greater C-reactive protein levels. Virus-positive exacerbations had a lower acute
      fall in FEV1 than virus-negative exacerbations (12.7% vs 15.6%; p=0.040). The
      incidence of exacerbations, but not VRI, was associated with greater lung
      function decline over 12 months (-1.79% per pulmonary exacerbation/year; 95% CI 
      3.4 to -0.23; p=0.025). CONCLUSION: VRI is common in adults with CF and is
      associated with substantial morbidity. Respiratory viruses are a potential
      therapeutic target in CF lung disease.

PMID- 24127020
TI  - Connective tissue disease related fibrotic lung disease: high resolution computed
      tomographic and pulmonary function indices as prognostic determinants.
AB  - PURPOSE: To determine high resolution computed tomography (HRCT) patterns and
      pulmonary function indices which are associated with increased mortality in
      patients with connective tissue disease related fibrotic lung disease (CTD-FLD).
      METHODS: HRCTs from 168 patients with CTD-FLD were scored by 2 observers for a
      variety of HRCT patterns and traction bronchiectasis. A radiological diagnosis of
      usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia
      (NSIP) or indeterminate was also assigned. Using Cox regression analysis,
      associations with mortality were identified. Honeycombing and traction
      bronchiectasis scores were converted to binary absence/presence scores and also
      tested. A subgroup analysis of patients with biopsy material (n=51) was performed
      by classifying patients according to radiological and histopathological
      diagnoses, as concordant UIP, discordant UIP and fibrotic NSIP. The prognostic
      separation of this classification was also evaluated. RESULTS: Severity of
      traction bronchiectasis (HR 1.10, p=0.001, 95% CIs 1.04 to 1.17), increasing
      extent of honeycombing (HR 1.08, p=0.021, 95% CI 1.03 to 1.13) and reduction in
      DLco (HR 0.97, p=0.013, 95% CI 0.95 to 0.99) were independently associated with
      increased mortality. Interobserver agreement and prognostic strength were higher
      for binary traction bronchiectasis scores (weighted kappa (kappaw)=0.69, HR 4.00,
      p=0.001, 95%CI 1.19 to 13.38), than binary honeycombing scores (kappaw=0.50, HR
      2.87, p=0.022, 95% CI 1.53 to 5.43). The radiological-histopathological
      classification was strongly associated with increased mortality (HR 2.74,
      p<0.001, 95% CI 1.57 to 4.77) and patients with discordant UIP had a better
      prognosis than concordant UIP but worse prognosis than fibrotic NSIP.
      CONCLUSIONS: Severity of traction bronchiectasis, extent of honeycombing and DLco
      are strongly associated with mortality in CTD-FLD. Interobserver agreement for
      traction bronchiectasis is higher than for honeycombing. In CTD-FLD, radiological
      diagnosis has survival implications in biopsy proven UIP.

PMID- 24127021
TI  - Rhinovirus-induced interferon production is not deficient in well controlled
      asthma.
AB  - BACKGROUND: Defective rhinovirus (RV)-induced interferon (IFN)-beta and IFN
      lambda production and increased RV replication have been reported in primary
      human bronchial epithelial cells (HBECs) from subjects with asthma. How universal
      this defect is in asthma is unknown. Additionally, the IFN subtypes induced by RV
      infection in primary HBECs have not been comprehensively investigated. OBJECTIVE:
      To study RV induction of IFN-alpha, IFN-beta and IFN-lambda and RV replication in
      HBECs from subjects with atopic asthma and healthy controls. METHODS: HBECs were
      obtained from subjects with asthma and healthy controls and infected with RV16
      and RV1B, and cells and supernatants harvested at 8, 24 and 48h. IFN proteins
      were analysed by ELISA and IFN mRNA and viral RNA expression by quantitative PCR.
      Virus release was assessed in cell supernatants. RESULTS: IFN-beta and IFN-lambda
      were the only IFNs induced by RV in HBECs and IFN-lambda protein induction was
      substantially greater than IFN-beta. Induction of IFN-lambda1 mRNA by RV16 at 48h
      was significantly greater in HBECs from subjects with asthma; otherwise there
      were no significant differences between subjects with asthma and controls in RV
      replication, or in induction of type I or III IFN protein or mRNA. CONCLUSIONS:
      IFN-lambda and, to a lesser degree, IFN-beta are the major IFN subtypes induced
      by RV infection of HBECs. Neither defective IFN induction by RV nor increased RV
      replication was observed in the HBECs from subjects with well controlled asthma
      reported in this study.

PMID- 24127022
TI  - Authors' response to Walker et al.

PMID- 24127023
TI  - The 'anatomic shunt test' in clinical practice; contemporary description of test
      and in-service evaluation.
AB  - The 100% oxygen shunt test for detecting right-to-left anatomical shunting was
      originally described 70 years ago. However, its clinical value is not yet
      established. We conducted an audit in 80 patients undergoing the test between
      1996 and 2012 in a tertiary referral centre. A significant difference (p=0.02)
      existed between the median shunt percentages where anatomical shunting was
      identified (10.2%) and absent (5.0%). The area under the curve for a ROC plot was
      0.70. A shunt percentage of 8.3 had a sensitivity of 80% and specificity of 75%
      for detection of an anatomic shunt. We conclude the test is satisfactory for the
      first-line investigation for anatomic shunting.

PMID- 24127024
TI  - The agro-ecological suitability of Atriplex nummularia and A. halimus for biomass
      production in Argentine saline drylands.
AB  - The choice of the best species to cultivate in semi-arid and arid climates is of
      fundamental importance, and is determined by many factors, including temperature
      and rainfall, soil type, water availability for irrigation and crop purposes.
      Soil or water salinity represents one of the major causes of crop stress. Species
      of the genus Atriplex are characterized by high biomass productivity, high
      tolerance to drought and salinity, and high efficiency in use of solar radiation
      and water. Based on a search of the international literature, the authors outline
      an agro-climatic zoning model to determine potential production areas in
      Argentina for Atriplex halimus and Atriplex numularia. Using the agroclimatic
      limits presented in this work, this model may be applied to any part of the
      world. When superimposed on the saline areas map, the agroclimatic map shows the
      suitability of agro-ecological zoning for both species for energy purposes on
      land unsuitable for food production. This innovative study was based on the
      implementation of a geographic information system that can be updated by further
      incorporation of complementary information, with consequent improvement of the
      original database. 

PMID- 24127025
TI  - [Comparison of susceptibility artifacts generated by microchips with different
      geometry at 1.5 Tesla magnet resonance imaging. A phantom pilot study referring
      to the ASTM standard test method F2119-07].
AB  - OBJECTIVE: Ferromagnetic material in microchips, used for animal identification,
      causes local signal increase, signal void or distortion (susceptibility artifact)
      on MR images. To measure the impact of microchip geometry on the artifact's size,
      an MRI phantom study was performed. MATERIAL AND METHODS: Microchips of the
      labels Datamars(r), Euro-I.D.(r) and Planet-ID(r) (n  =  15) were placed
      consecutively in a phantom and examined with respect to the ASTM Standard Test
      Method F2119-07 using spin echo (TR 500 ms, TE 20 ms), gradient echo (TR 300 ms,
      TE 15 ms, flip angel 30 degrees ) and otherwise constant imaging parameters
      (slice thickness 3 mm, field of view 250 x 250 mm, acquisition matrix 256 x 256
      pixel, bandwidth 32 kHz) at 1.5 Tesla. Image acquisition was undertaken with a
      microchip positioned in the x- and z-direction and in each case with a phase
      encoding direction in the y- and z-direction. The artifact size was determined
      with a) a measurement according to the test method F2119-07 using a homogeneous
      point operation, b) signal intensity measurement according to Matsuura et al. and
      c) pixel counts in the artifact according to Port and Pomper. RESULTS: There was
      a significant difference in artifact size between the three microchips tested
      (Wilcoxon p = 0.032). A two- to three-fold increase in microchip volume generated
      an up to 76% larger artifact, depending on the sequence type, phase-encoding
      direction and chip position to B0. CONCLUSION AND CLINICAL RELEVANCE: The smaller
      the microchip geometry, the less is the susceptibility artifact. Spin echoes (SE)
      generated smaller artifacts than gradient echoes (GE). In relation to the spatial
      measurement of the artifact, the switch in phase-encoding direction had less
      influence on the artifact size in GE- than in SE-sequences. However, the artifact
      shape and direction of SE-sequences can be changed by altering the phase. The
      artifact size, caused by the microchip, plays a major clinical role in the
      evaluation of MRI from the head, shoulder and neck regions.

PMID- 24127026
TI  - The Rivalta's test as a diagnostic variable in feline effusions--evaluation of
      optimum reaction and storage conditions.
AB  - OBJECTIVE: The Rivalta's test is used to diagnose feline infectious peritonitis
      (FIP) in cats with effusion. Only little information on the influence of sample
      storage and reaction conditions on test results is available, and diagnostic
      sensitivity and specificity to diagnose FIP vary considerably between few
      available studies. This study determined the influence of storage of effusion,
      modifications on reaction conditions, and inter-observer variation. MATERIAL AND
      METHODS: The Rivalta's test was repeated up to 21 days after storage at room
      temperature, in the refrigerator, or freezer. The test was performed by two
      independent, blinded investigators. It was also performed using different volumes
      of acetic acid, different acids, and different kinds of water. RESULTS: Even
      after storage for 21 days, test results were comparable. While inter-observer
      variation revealed substantial disagreement, different modifications in
      performance showed no major influence on test outcome. CONCLUSION: The Rivalta's
      test seems to be a very robust test concerning storage conditions. Modifications
      in reaction condition also do not substantially influence outcome. However, the
      test is subjective and depends on the evaluating person.

PMID- 24127027
TI  - [Results of a survey regarding the publication of scientific results in German
      speaking countries].
AB  - OBJECTIVE: Veterinarians should conduct diagnostic and therapeutic procedures
      according to the most recent and scientifically proven methods. Therefore, a
      rapid and effective transfer of scientific information is crucial. An important
      link between science and practice are findings published in scientific journals.
      The productivity of scientists is often measured referring to the number of
      papers published in reputable journals. Because many of these journals publish in
      the English language, it is possible that results from German research may never
      reach German veterinarians or only after a delay. MATERIAL AND METHODS: Using an
      online questionnaire, faculty members (professors and scientific assistants) from
      Germany, Austria and Switzerland were asked how they had published their results
      during the previous 5 years. Furthermore, they were asked to identify the factors
      influencing their choice of journal for publication. RESULTS: A total of 118
      respondents completed the questionnaire. Nearly two thirds had published ten or
      more papers during the previous 5 years. More than half of these were published
      in the English language. Most participants consider the peer review process
      suitable for enhancing the quality of publications. The impact factor is seen as
      a fair indicator for the quality of a paper while considered an important factor
      for the choice of a journal for publication of the respondents own results.
      CONCLUSION AND CLINICAL RELEVANCE: According to the data, respondents prefer to
      publish their results in the English language and in journals with a high impact
      factor. Therefore, veterinarians may never receive this information via German
      journals or only after a delay. One possible solution could be a regularly
      published practice-oriented compilation of relevant scientific findings.

PMID- 24127028
TI  - [Radiographic findings in raptors affected with a mycosis of the respiratory
      tract].
AB  - OBJECTIVE: Summary of typical radiographic signs in birds of prey with
      aspergillosis compared to signs previously established in parrots. MATERIALS AND
      METHODS: Evaluation of radiographs of 110 falcons (Falco spp.) with aspergillosis
      confirmed by endoscopy. RESULTS: Compared to parrots primarily subtle
      radiographic signs were detected in falcons (especially inhomogeneously increased
      radiodensities of the airsacs/lungs). Two typical signs for diseased falcons
      consisted of the poor delineation of the cardiac silhouette and the line-shaped
      increased radiodensity of the caudal lung border. Radiographic diagnosis of the
      lung is limited due to the strong flight musculature. CONCLUSION: The varying
      results between avian species can be explained by the different radiographic
      anatomy, husbandry conditions and x-ray technique (digital versus analog).
      CLINICAL RELEVANCE: A pet bird-experienced practitioner should be aware of
      specific radiographic signs in birds of prey suspected of having aspergillosis.

PMID- 24127029
TI  - [Examinations on the pharmacokinetics and compatibility of enalapril in racing
      pigeons].
AB  - OBJECTIVE: It was the aim of this study to examine the compatibility and the
      pharmacokinetics of the angiotensin converting enzyme inhibitor enalapril after
      oral application in racing pigeons and Amazons, and to contribute to a safe
      dosage regime of this drug in birds. MATERIAL AND METHODS: For the examination of
      drug compatibility, three groups of pigeons (n = 8 each) received enalapril into
      the crop at a dose of 5 or 10 mg/kg body weight, or placebo, respectively. Health
      status, and water and food consumption were monitored regularly, and clinical,
      hematological and blood-chemical parameters were determined. To determine a
      suitable starting dosage, birds were treated with enalapril at a dose of 2.5
      mg/kg (first trial) and 1.25 mg/kg (second trial), and blood samples were
      collected at defined time points. Using high performance liquid chromatography
      (HPLC), the enalapril concentration in the plasma samples was determined.
      RESULTS: Drug application did not cause any significant drug-related difference
      between the groups. Nearly all measured parameters were found to be within normal
      physiological ranges. Only for hematocrit was a slight but significant increase
      found for the group treated with 5 mg/kg enalapril. In pigeons, after application
      of 2.5 mg/kg enalapril, the maximum plasma concentration was found in the first
      sample taken (388.2 +/- 174.1 mg/kg). The application of 1.25 mg/kg resulted in a
      maximum concentration of 116.1 +/- 70.2 ng/ml after 30 minutes in pigeons. In the
      Amazon birds, the maximum value was found after 1 hour (first sampling) of 43.3
      +/-6.0 ng/ml. In all examinations, the enalapril concentration was <15 ng/ml
      after 8 hours. The terminal half-life was 2.68 hours for pigeons and 2.36 hours
      for Amazons. CONCLUSION: The results underline the good compatibility of
      enalapril after oral administration in healthy pigeons. A starting dosage of 1.25
      mg/kg enalapril given twice daily can be recommended. CLINICAL RELEVANCE: The
      study provides basic data (compatibility and pharmacokinetics) for the
      application of enalapril in birds such as the racing pigeon.

PMID- 24127030
TI  - [Nematode infections of the respiratory tract in dogs in Germany].
AB  - Recent studies have shown that the risk of lungworm infection may have increased
      in dogs in Germany in recent years. Analysis of the fecal examination of dogs has
      shown that Angiostrongylus vasorum, Crenosoma vulpis and Eucoleus aerophilus are
      endemic in Germany. Infections with A. vasorum were diagnosed in 223 of the
      examined dogs. A total of 102 A. vasorum-positive dogs were located in Baden
      Wuerttemberg, 65 in North Rhine-Westphalia, 27 in Saarland, 15 in Bavaria, 7 in
      Rhineland-Palatinate, 5 in Hessen and 2 in Brandenburg. A total of 170 dogs were
      infected with C. vulpis, 54 of which came from North Rhine-Westphalia, 40 from
      Baden-Wuerttemberg, 30 from Bavaria, 17 from Rhineland-Palatinate, 17 from
      Saarland, 9 from Hessen and 1 each from Lower Saxony, Berlin and Mecklenburg
      Western Pomerania. Infections with E. aerophilus were detected in 83 dogs, of
      which 23 lived in Baden-Wuerttemberg, 20 in North Rhine-Westphalia, 17 in
      Bavaria, 11 in Rhineland-Palatinate, 7 in Hessen, 4 in Saarland and 1 in
      Mecklenburg-Western Pomerania. Lungworm infections in dogs appear to be well
      established in Germany. The aim of the study presented was to assess the main
      facts, occurrence, geographical distribution, clinical signs, diagnosis and
      therapy of lungworm infections in dogs. 

PMID- 24127031
TI  - Ultrasound-aided diagnosis of an insulinoma in a cat.
AB  - A 15-year old, neutered female, domestic shorthaired cat was presented for
      evaluation of a 3-month history of paroxysmal falling over and trembling. In
      laboratory work the cat displayed a mild hypoglycemia. Ultrasound revealed a
      nodule in the left pancreatic lobe and surgical excision was performed. The
      histological diagnosis was an insulinoma. To the authors knowledge this is the
      first ultrasound description of an insulinoma in a cat. Up to date the cat has a
      survival time of 32 months without recurrence of symptoms. 

PMID- 24127032
TI  - [Subclinical alveolar echinococcosis in a dog initially showing clinical features
      of leptospirosis].
AB  - A 3.5-year-old male Labrador retriever dog showed a short history of illness
      characterized by vomiting, apathy, and fever. Ultrasonographically, large nodular
      liver masses of high echogenicity were noted in both left and right liver lobes.
      Cytological and bacteriological examinations revealed a neutrophilic hepatitis
      without detectable agents. During treatment with doxycycline a four-fold decrease
      of serum titers to Leptospira (L.) icterohaemorrhagiae and L. sejroe was detected
      in paired serum samples by use of the complement-fixation test. The dog remained
      without clinical signs and no significant biochemical changes were recorded.
      However, ultrasonsographic examinations showed a progression of the hepatic
      lesions, presenting now as nodular parts with high echogenicity and cavernous
      parts with lower echogenicity. Diagnostic laparotomy was performed and the dog
      was euthanized due to severity of hepatic lesions. Histopathologically, a severe
      chronic granulomatous hepatitis with numerous parasitic structures was diagnosed.
      Morphology of the parasitic structures was comparable to the metacestode stage of
      Echinococcus multilocularis. 

PMID- 24127033
TI  - [Musculotendinopathy of the gastrocnemius muscle in a Labrador Retriever. A case
      report].
AB  - Musculotendinopathy at the origin of the gastrocnemius muscle is a rare disease
      mostly described in herding dogs. The etiology is based on repeated myotendinous
      strain of the muscle in athletic dogs. Clinically, the patient displays chronic
      pelvic limb lameness and pain at the lateral fabella during palpation of this
      area. There is no instability of the stifle present. Radiographic findings
      (osteophyte formation at the origin of the muscle and the lateral fabella)
      support the potential diagnosis. Magnetic resonance tomography shows edematous
      changes and enhancement after intravenous application of contrast agent in the
      area of the origin of the lateral gastrocnemius head. With conservative treatment
      (i. e. leash confinement, NSAID application and physiotherapy) the prognosis is
      good. This case report describes clinical findings, diagnostic imaging, therapy
      and long-term outcome of an athletic Labrador Retriever presented with this
      disease. 

PMID- 24127034
TI  - Masculine men articulate less clearly.
AB  - In previous research, acoustic characteristics of the male voice have been shown
      to signal various aspects of mate quality and threat potential. But the human
      voice is also a medium of linguistic communication. The present study explores
      whether physical and vocal indicators of male mate quality and threat potential
      are linked to effective communicative behaviors such as vowel differentiation and
      use of more salient phonetic variants of consonants. We show that physical and
      vocal indicators of male threat potential, height and formant position, are
      negatively linked to vowel space size, and that height and levels of circulating
      testosterone are negatively linked to the use of the aspirated variant of the
      alveolar stop consonant /t/. Thus, taller, more masculine men display less
      clarity in their speech and prefer phonetic variants that may be associated with
      masculine attributes such as toughness. These findings suggest that vocal signals
      of men's mate quality and/or dominance are not confined to the realm of voice
      acoustics but extend to other aspects of communicative behavior, even if this
      means a trade-off with speech patterns that are considered communicatively
      advantageous, such as clarity and indexical cues to higher social class. 

PMID- 24127035
TI  - Strong adhesiveness of a new biodegradable hydrogel glue, LYDEX, for use on
      articular cartilage.
AB  - AIM: Until recently, only fibrin glue has been available for clinical usage to
      repair articular cartilage, although its adhesiveness is not strong enough for
      use with articular cartilage, and it is derived from human blood and thus carries
      the risk of contamination. Recently, LYDEX, a new biodegradable hydrogel glue,
      has come onto the market. The purpose of this study was to evaluate the adhesive
      strength and cytotoxicity of LYDEX when used on articular cartilage. MATERIALS
      AND METHODS: The differing adhesive strengths of collagen membrane and articular
      cartilage with LYDEX versus with fibrin glue were measured using a tensile
      tester. In addition, the cytotoxicity of LYDEX in vitro was evaluated. The
      cytotoxicity of LYDEX for the articular cartilage of rats was evaluated
      histopathologically. RESULTS: The adhesive strength of LYDEX was significantly
      stronger than that of fibrin glue, giving values about 3.8 times higher. LYDEX
      has no discernible effect on normal articular cartilage. CONCLUSIONS: Our study
      is the first to assess the usefulness and safety of LYDEX for use on articular
      cartilage.

PMID- 24127036
TI  - Shear bond strength of self-adhering flowable composite on dentin with and
      without application of an adhesive system.
AB  - PURPOSE: The aim of this study was to evaluate the shear bond strength (SBS) of
      conventional and self-adhering flowable resin composites on the dentin surfaces
      of primary and permanent teeth and to evaluate the effect of the application of
      an adhesive system under self-adhering flowable resin composite on SBS. METHODS:
      Prepared permanent and primary tooth dentin surfaces were randomly distributed
      into 3 groups according to application protocols as follows: group 1: Vertise
      Flow; group 2: OptiBond + Filtek Ultimate; and group 3: OptiBond + Vertise Flow.
      A universal testing machine was used to measure SBS of prepared specimens, and
      data were analyzed using 1-way ANOVA and Tukey test. RESULTS: Statistically
      significant differences were observed among all groups for primary and permanent
      teeth (P<0.05). The highest values were observed in group 2, followed by group 3,
      in both permanent and primary teeth. SBSs of all groups were significantly higher
      for permanent teeth than for primary teeth (P<0.05). CONCLUSION: Although SBS
      values of Vertise Flow groups were lower than those for conventional flowable
      resin composite groups, with further developments in material technology, self
      adhering materials could be promising materials especially for pediatric
      dentistry.

PMID- 24127037
TI  - Application of polymer nanocomposites in the nanomedicine landscape: envisaging
      strategies to combat implant associated infections.
AB  - This review article presents an overview of the potential biomedical application
      of polymer nanocomposites arising from different chemistries, compositions, and
      constructions. The interaction between the chosen matrix and the filler is of
      critical importance. The existing polymer used in the biomedical arena includes
      aliphatic polyesters such as polylactide (PLA), poly(epsilon-caprolactone) (PCL),
      poly(p-dioxanone) (PPDO), poly(butylenes succinate) (PBS),
      poly(hydroxyalkanoate)s, and natural biopolymers such as starch, cellulose,
      chitin, chitosan, lignin, and proteins. The nanosized fillers utilized to
      fabricate the nanocomposites are inorganic, organic, and metal particles such as
      clays, magnetites, hydroxyapatite, nanotubes chitin whiskers, lignin, cellulose,
      Au, Ag, Cu, etc. These nanomaterials are taking root in a variety of diverse
      healthcare applications in the sector of nanomedicine including the domain of
      medical implants and devices. Despite sterilization and aseptic procedures the
      use of these biomedical devices and prosthesis to improve the patient's 'quality
      of life' is facing a major impediment because of bacterial colonization causing
      nosocomial infection, together with the multi-drug-resistant 'super-bugs' posing
      a serious threat to its utility. This paper discusses the current efforts and key
      research challenges in the development of self-sterilizing nanocomposite
      biomaterials for potential application in this area.

PMID- 24127038
TI  - Associations between vascular endothelial growth factor polymorphisms and
      prostate cancer risk: a meta-analysis.
AB  - Angiogenesis is crucial for the development and metastasis of common cancers, and
      vascular endothelial growth factor (VEGF) is a key mediator in the process of
      angiogenesis. Numerous studies assessed the associations of VEGF 1154G/A and
      2578C/A polymorphisms with prostate cancer risk, but the results were
      inconsistent. We performed a meta-analysis to investigate the possible
      associations. Relevant studies were searched in PubMed and Embase databases. The
      pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to
      evaluate the associations. Finally, eight individual case-control studies from
      seven publications were finally included into the meta-analysis. There were a
      total of 3,879 cases and 4,285 controls from those eight studies. Meta-analysis
      of those four case-control studies for VEGF 1154G/A polymorphism showed that VEGF
      1154G/A polymorphism was weakly associated with risk of prostate cancer under the
      allele model (A versus G: OR = 0.68, 95 % CI 0.46-1.00, P = 0.05). Meta-analysis
      of four case-control studies for VEGF 2578C/A polymorphism showed that there was
      an association between VEGF 2578C/A polymorphism and prostate cancer under the
      recessive model (AA versus CC/CA: OR = 1.53, 95 % CI 1.01-2.30, P = 0.04).
      However, there was no obvious association in the other comparison models.
      Therefore, there is limited evidence for the associations of VEGF 1154G/A and
      2578C/A polymorphisms with prostate cancer risk, and more studies are needed to
      further assess the associations above.

PMID- 24127039
TI  - WW domain containing oxidoreductase induces apoptosis in gallbladder-derived
      malignant cell by upregulating expression of P73 and PUMA.
AB  - Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide.
      WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can
      suppress proliferation of a variety of tumors. However, little was known about
      the relationships between WWOX and gallbladder cancer. In the current study, we
      intended to investigate the tumor suppressive role of WWOX in gallbladder
      malignant cells both in vitro and in vivo, and explore the potential mechanism of
      tumor toxic function of WWOX. Our results have shown that WWOX triggerred
      apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm.
      We also have found that Bax has been upregulated after overexpression of WWOX,
      whereas, Bcl-2 was downregulated by WWOX. To further validate the results in
      vivo, we evaluated the tumor suppressive role of WWOX in mouse model of
      gallbladder cancer. The results have shown that the proliferation of the tumor
      was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were
      upregulated in target tissues. The mice models administrated with WWOX have shown
      better prognosis than mice in negative control groups. The results from our study
      indicated that WWOX could be used as a therapeutic agent in the gene therapy of
      gallbladder cancer.

PMID- 24127040
TI  - miR-133a suppresses ovarian cancer cell proliferation by directly targeting
      insulin-like growth factor 1 receptor.
AB  - The microRNA miR-133a is dysregulated in many types of cancer, but the underlying
      mechanism remains largely unknown. In this study, we showed that the expression
      level of miR-133a was reduced in ovarian cancer tissues compared with normal
      ovaries. Ectopic expression of miR-133a significantly inhibited ovarian cancer
      cell proliferation and colony formation, and induced G1-phase cell cycle arrest,
      whereas decreased miR-133a expression dramatically enhanced cell proliferation
      and colony formation. Importantly, miR-133a overexpression suppressed in vivo
      tumor growth in nude mice models. Through in silico search, we found that the 3'
      untranslated region (UTR) of insulin-like growth factor 1 receptor (IGF1R)
      contains an evolutionarily conserved miR-133a binding site. miR-133a
      overexpression repressed IGF1R-3'UTR reporter activity, and reduced the mRNA and
      protein levels of endogenous IGF1R. Rescue experiments showed that ectopic
      expression of IGF1R significantly promoted the proliferation of ovarian cancer
      cells stably overexpressing miR-133a. Taken together, these findings indicate
      that miR-133a is an important regulator in ovarian cancer, and that its
      suppressive effects are mediated by targeting IGF1R. 

PMID- 24127041
TI  - Polymorphisms in ESR1 and FLJ43663 are associated with breast cancer risk in the
      Han population.
AB  - Breast cancer is a heterogeneous disease which is influenced by genetic,
      environmental, and lifestyle factors. Genetic susceptibility is likely to be due
      to variants conferring more moderate risks. To identify susceptibility alleles,
      we conducted a case-control association study in 185 breast cancer cases and 199
      controls in the Han population. We genotyped 14 tagging single nucleotide
      polymorphisms previously implicated in breast cancer using Sequenom MassARRAY SNP
      genotyping method and identified rs3734805 in the ESR1 gene and rs2048672 in the
      FLJ43663 gene were associated with breast cancer risk. Allele "C" of rs3734805
      was associated with increased breast cancer progression by chi (2) test and
      additive model analysis (OR = 1.36; 95% CI, 1.01-1.82; p = 0.042). Using
      recessive model analysis, we found that genotype "GG" of rs2048672 was the
      protective genotype during breast cancer progression (OR = 0.55; 95% CI, 0.32
      0.95; p = 0.029). Our results provide additional insights into the opposing roles
      of the ESR1 and FLJ43663 genes in breast cancer onset and progression.

PMID- 24127043
TI  - Post-anastomotic rectovesical fistula: endoscopic treatment by OTSC ((r)).

PMID- 24127042
TI  - Pathways of Toxicity.
AB  - Despite wide-spread consensus on the need to transform toxicology and risk
      assessment in order to keep pace with technological and computational changes
      that have revolutionized the life sciences, there remains much work to be done to
      achieve the vision of toxicology based on a mechanistic foundation. To this end,
      a workshop was organized to explore one key aspect of this transformation - the
      development of Pathways of Toxicity as a key tool for hazard identification based
      on systems biology. Several issues were discussed in depth in the workshop: The
      first was the challenge of formally defining the concept of a Pathway of Toxicity
      (PoT), as distinct from, but complementary to, other toxicological pathway
      concepts such as mode of action (MoA). The workshop came up with a preliminary
      definition of PoT as "A molecular definition of cellular processes shown to
      mediate adverse outcomes of toxicants". It is further recognized that normal
      physiological pathways exist that maintain homeostasis and these, sufficiently
      perturbed, can become PoT. Second, the workshop sought to define the adequate
      public and commercial resources for PoT information, including data,
      visualization, analyses, tools, and use-cases, as well as the kinds of efforts
      that will be necessary to enable the creation of such a resource. Third, the
      workshop explored ways in which systems biology approaches could inform pathway
      annotation, and which resources are needed and available that can provide
      relevant PoT information to the diverse user communities.

PMID- 24127044
TI  - Invited comment on Warrier et al: hereditary colorectal cancer screening and
      management practices by colorectal surgeons.

PMID- 24127045
TI  - [The new face of ENT allergology].

PMID- 24127046
TI  - [The NTP in allergy research : open questions regarding nasal provocation tests
      using allergens].
AB  - The nasal provocation test (NPT) is a simple procedure with high specificity and
      sensitivity that is used in the investigation of allergic and nonallergic
      diseases. Uniform standards are of particular importance in the clinical setting
      and for the comparability of clinical and basic allergy research. These standards
      should cover the composition, dosage and pharmacological formulation of
      provocative substances (e.g. allergen extracts), the necessity of titration,
      allergen application methods and the evaluation criteria for a positive NPT
      reaction. Detection of various mediators and cytokines in nasal discharge can be
      very useful in the late phase reactions. NPT finds specific applications in
      studies of local IgE secretion in the nasal mucosa, the diagnosis of analgesic
      intolerance and in assessments of the efficacy of specific immunotherapies.
      Additional parameters warranting further evaluation include provocation with cold
      dry air in nasal hyperreactivity patients and nasal nitric oxide formation.
      Determination of nasal blood flow during NPT provides an additional clinical
      parameter. 

PMID- 24127047
TI  - [Immunotherapy of allergic rhinitis without allergens? : new options for
      immunomodulation by vaccination with virus-like particles and CpG motifs].
AB  - BACKGROUND: Allergen-specific immunotherapy is generally accepted as the only
      causal therapy for allergic rhinitis. Up to now there has been a dogma in
      immunotherapy for inhalation allergies that at least allergen components are
      necessary for effective therapy. This dogma could, however, be swayed by current
      results of effective immunotherapy without allergens. Virus-like particles (VLP)
      represent a novel and interesting aspect for immunotherapy for inhalation
      allergies. AIM: Initial experiences with successful immunotherapy without
      allergens are available. This article describes the currently available clinical
      experiences with bacteriophage VLPs filled with oligonucleotides which contain
      CpG motifs with tumor antigens on the surface for the treatment of allergic
      rhinitis. RESULTS: Vaccination with VLPs was found to be well tolerated,
      immunogenic and effective for prophylactic treatment of various infections.
      Bacteriophage VLPs filled with CpG motifs with tumor antigens on the surface led
      clinically to an induction of specific T-cells in tumor patients and were
      successfully implemented as adjuvants during prophylactic vaccinations.
      CONCLUSION: The VLP technique in combination with the use of CpG motifs could
      contribute to the causal treatment of complex diseases, such as malignancies,
      autoimmune diseases and allergies.

PMID- 24127048
TI  - [Aspects of avoiding recurrence after endoscopic dacryocystorhinostomy].

PMID- 24127049
TI  - [Bleeding tumor of the auricle].

PMID- 24127050
TI  - [Medical examination: preparation for ENT specialisation : part 11].

PMID- 24127051
TI  - [Management of postoperative pain in ear-nose-throat surgery].
AB  - The degree of pain following different types of ear-nose-throat surgery varies
      greatly and must be adjusted on an individual basis. Post-operative pain therapy
      can be classified into basic pain therapy and additive pain therapy (as needed).
      Effective pain therapy can lead to lower morbidity and to considerable economic
      advantages. The subjective pain intensity experienced by patient should be the
      basis for the dose adaptation and is essential for rapid recovery. 

PMID- 24127053
TI  - [Willingness to accept an Internet-based mobility platform in different age
      cohorts. Empiric results of the project S-Mobil 100].
AB  - BACKGROUND: The aim of the project S-Mobil 100 is to develop and implement a
      prototype of an internet-based, generation-appropriate mobility platform in the
      model region Siegen-Wittgenstein. In the context of an empirical preliminary
      study, use of technology, experience with technology, general attitudes towards
      technology, general technology commitment, and the willingness to accept the
      mobility platform were investigated in different age cohorts. PATIENTS AND
      METHODS: The investigation was carried out using a written survey based on a
      standardized questionnaire. The sample of 358 persons aged 40-90 years was
      divided in four age cohorts (40-54, 55-64, 65-74, and 75 + years). RESULTS: Our
      results show a high willingness to accept the mobility platform in the overall
      sample. Age, residence, income, and general technology commitment were
      significant predictors for the judgment of the platform. CONCLUSION: Although
      there were group differences in accepting the mobility platform, the older
      cohorts are also open-minded towards this new technology.

PMID- 24127052
TI  - Occupational therapy for elderly. Evidence mapping of randomised controlled
      trials from 2004-2012.
AB  - OBJECTIVE: Previous systematic reviews on occupational therapy for elderly
      included studies until 2003. The present evidence mapping summarizes recent
      evidence for the efficacy of occupational therapy with older persons based on
      randomised controlled trials from 2004-2012. METHOD: An electronic search in
      Cochrane and Medline databases identified publications of randomised controlled
      trials on occupational therapy interventions for persons>=65 years old. Two
      raters independently extracted data and analysed the quality of samples,
      interventions and outcome evalutations according to PRISMA criteria. RESULTS: In
      all, 136 abstracts were identified and 48 studies analysed, from these 12 on
      stroke, 15 on falls and mobility, 7 on dementia, 4 on prevention and 10 on other
      conditions. Reports of adverse events and evaluations of costs and long-term
      outcomes are frequently lacking. CONCLUSION: The most promising fields for
      further research are primary and secondary prevention in persons with stroke,
      falls or mobility problems and tertiary prevention in persons with dementia.
      Future trials should be conducted and reported according to consented reporting
      guidelines of the equator network.

PMID- 24127054
TI  - Food-dependent exercise-induced anaphylaxis: is wheat unique?
AB  - This review draws comparisons between wheat-dependent exercise-induced
      anaphylaxis (WDEIA) and other food-dependent exercise-induced anaphylaxis
      (FDEIAs) and discusses the importance of co-factors in its pathophysiology. FDEIA
      remains an enigmatic condition since it was first described 30 years ago. The
      sporadic and unpredictable nature of its reactions has puzzled clinicians and
      scientists for decades, but recent studies on WDEIA have enlightened us about the
      pathophysiology of this condition. The identification of defined allergic
      epitopes such as Tri a 19, alpha-gliadin, beta-gliadin and gamma-gliadin in WDEIA
      enables it to become the perfect model for studying FDEIA, but WDEIA is by no
      means a unique condition. On a larger scale, FDEIA represents a crucial link
      between IgE-mediated and anaphylactoid reactions and provides supportive evidence
      for the concept of 'summation anaphylaxis' and the need to overcome the 'allergen
      threshold'. Future work should focus on identifying more of the FDEIA epitopes
      and understanding their distinct molecular properties. The development of a
      biomarker in order to identify patients susceptible to co-factor influences would
      be invaluable. 

PMID- 24127055
TI  - Cloning, phylogeny, and regional expression of a Y5 receptor mRNA in the brain of
      the sea lamprey (Petromyzon marinus).
AB  - The NPY receptors known as Y receptors are classified into three subfamilies, Y1,
      Y2, and Y5, and are involved in different physiological functions. The Y5
      receptor is the only member of the Y5 subfamily, and it is present in all
      vertebrate groups, except for teleosts. Both molecular and pharmacological
      studies show that Y5 receptor is highly conserved during vertebrate evolution.
      Furthermore, this receptor is widely expressed in the mammalian brain, including
      the hypothalamus, where it is thought to take part in feeding and homeostasis
      regulation. Lampreys belong to the agnathan lineage, and they are thought to have
      branched out between the two whole-genome duplications that occurred in
      vertebrates. Therefore, they are in a key position for studies on the evolution
      of gene families in vertebrates. Here we report the cloning, phylogeny, and brain
      expression pattern of the sea lamprey Y5 receptor. In phylogenetic studies, the
      lamprey Y5 receptor clusters in a basal position, together with Y5 receptors of
      other vertebrates. The mRNA of this receptor is broadly expressed in the lamprey
      brain, being especially abundant in hypothalamic areas. Its expression pattern is
      roughly similar to that reported for other vertebrates and parallels the
      expression pattern of the Y1 receptor subtype previously described by our group,
      as it occurs in mammals. Altogether, these results confirm that a Y5 receptor is
      present in lampreys, thus being highly conserved during the evolution of
      vertebrates, and suggest that it is involved in many brain functions, the only
      known exception being teleosts.

PMID- 24127056
TI  - Empowering Nurses to Participate in Ethical Decision-Making at the Bedside.

PMID- 24127057
TI  - Knee Arthroscopy Cohort Southern Denmark (KACS): protocol for a prospective
      cohort study.
AB  - BACKGROUND: Meniscus surgery is a high-volume surgery carried out on 1 million
      patients annually in the USA. The procedure is conducted on an outpatient basis
      and the patients leave the hospital a few hours after surgery. A critical
      oversight of previous studies is their failure to account for the type of
      meniscal tears. Meniscus tears can be categorised as traumatic or non-traumatic.
      Traumatic tears (TT) are usually observed in younger, more active individuals in
      an otherwise 'healthy' meniscus and joint. Non-traumatic tears (NTT) (ie,
      degenerative tears) are typically observed in the middle-aged (35-55 years) and
      older population but the aetiology is largely unclear. Knowledge about the
      potential difference of the effect of arthroscopic meniscus surgery on patient
      symptoms between patients with traumatic and NTT is sparse. Furthermore, little
      is known about the natural time course of patient perceived pain, function and
      quality of life after meniscus surgery and factors affecting these outcomes. The
      aim of this prospective cohort study is to investigate the natural time course of
      patient-reported outcomes in patients undergoing meniscus surgery, with
      particular emphasis on the role of type of symptom onset. METHODS/DESIGN: This
      prospective cohort study enrol patients assigned for meniscus surgery. At the
      baseline (PRE surgery), patient characteristics are assessed using an email-based
      questionnaire also comprising several validated questionnaires assessing general
      health, knee-specific characteristics and patient's expectations of the surgery.
      Follow-up will be conducted at 12 and 52 weeks after meniscus surgery. The major
      outcomes will be differences in changes, from before to 52 weeks after surgery,
      in each of the five domains on the Knee injury and Osteoarthritis Outcome Score
      (KOOS) between patients undergoing surgery for traumatic compared with non
      traumatic meniscus tears. DISSEMINATION: The study findings will be disseminated
      in peer-reviewed journals and presented at national and international
      conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier:
      NCT01871272.

PMID- 24127058
TI  - Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Hospital-acquired pneumonia remains the most lethal and expensive
      nosocomial infection worldwide. Optimal therapy remains controversial. We aimed
      to compare mortality and clinical response outcomes in patients treated with
      either linezolid or vancomycin. DESIGN: Systematic review and meta-analysis. DATA
      SOURCES: PubMed, EMBASE, Cochrane Library, American College of Physicians Journal
      Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and
      critical care meetings were searched through April 2013. ELIGIBILITY CRITERIA FOR
      SELECTING STUDIES: All randomised clinical trials comparing linezolid to
      vancomycin for hospital-acquired pneumonia. DATA EXTRACTION: Preferred reporting
      items for systematic reviews and meta-analyses guidelines were followed. One
      author extracted the data and two authors rechecked and verified all data.
      RESULTS: Nine randomised trials with a total of 4026 patients were included. The
      adjusted absolute mortality risk difference (RD) between linezolid and vancomycin
      was 0.01% (95% CI -2.1% to 2.1%; p=0.992; I(2)=13.5%. The adjusted absolute
      clinical response difference was 0.9% (95% CI -1.2% to 3.1%; p=0.409; I(2)=0%.
      The risk of both microbiological (RD=5.6%, 95% CI -2.2% to 13.3%; p=0.159;
      I(2)=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI -4.1%
      to 16.9%; p=0.230; I(2)=0%) eradication were not different between linezolid and
      vancomycin. Gastrointestinal side effects were more frequent with linezolid
      (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal
      failure, thrombocytopenia and drug discontinuation due to adverse events. Our
      sample size provided 99.9% statistical power to detect differences between drugs
      regarding clinical response and mortality. CONCLUSIONS: Linezolid and vancomycin
      have similar efficacy and safety profiles. The high statistical power and the
      near-zero efficacy difference between both antibiotics demonstrates that no drug
      is superior for the treatment of hospital-acquired pneumonia.

PMID- 24127059
TI  - We Know in Part: James McCosh on Evolution and Christian Faith.
AB  - James McCosh (1811-1894), president of Princeton College from 1868 to 1888,
      played a significant role in the American reception of evolution in the late
      1800s - he was one of the more prominent clergyman to assuage the public's fears
      of evolution while incorporating evolution into a conservative Christian
      worldview. McCosh was a prolific writer, whose books document his intellectual
      journey from hostility to acceptance of evolution. Three things will stand out in
      this overview that have not been emphasized in detail in other works: (1) James
      McCosh's perspective on evolution dramatically changed over time; (2) McCosh's
      motivations for engaging in the evolution-religion debate serve to clear up
      confusion regarding McCosh's final position on evolution; and (3) the theological
      and philosophical basis for McCosh's acceptance of evolution was established
      while McCosh was still hostile to evolution. His theological background therefore
      'pre-adapted' him for evolution, and he was able to preach theology and evolution
      without substantially altering his theology. 

PMID- 24127060
TI  - Reply to: Doppler sonography as a potential screening tool for preanaesthetic
      evaluation.

PMID- 24127061
TI  - Analgesic efficacy of ultrasound-guided adductor canal blockade after
      arthroscopic anterior cruciate ligament reconstruction.

PMID- 24127062
TI  - Thermoelectric properties of spark-plasma sintered nanoparticular FeSb2 prepared
      via a solution chemistry approach.
AB  - Nanoparticular FeSb2 was prepared in solution from cyclopentadienyl iron(ii)
      dicarbonyl dimer [Fe(Cp(CO)2)]2 and antimony nanoparticles. Spark plasma
      sintering was used as consolidation method to maintain the particle size. The
      thermoelectric performance of FeSb2 is limited by its high thermal conductivity.
      In this work, the thermal conductivity was suppressed by nearly 80% compared to
      the bulk value by introducing grain boundary scattering of phonons on the
      nanoscale. The thermoelectric properties of the consolidated FeSb2 emphasize the
      possibility of altering thermal transport of promising thermoelectric compounds
      by phonon scattering by engineering the interfaces at the nanoscale. 

PMID- 24127063
TI  - Clinical implications of the SETBP1 mutation in patients with primary
      myelodysplastic syndrome and its stability during disease progression.
AB  - Mutations of the SET binding protein 1 (SETBP1) gene have been identified in
      patients with myeloid neoplasms, but the clinical relevance of this mutation and
      its association with other gene mutations in myelodysplastic syndrome (MDS) and
      the stability during disease progression remains unclear. Mutations in SETBP1
      gene at exon 4 were analyzed by polymerase chain reaction and direct sequencing
      in 430 MDS patients. The results were correlated with clinical features,
      cytogenetics, gene mutations and treatment outcomes. SETBP1 mutations were
      identified in 14 (3.3%) of the 430 patients with primary MDS based on the FAB
      classification and 8 (2.4%) of the 333 patients based on the WHO classification.
      The SETBP1 mutation was closely associated with higher white blood cell counts,
      isochromosome of 17q, monosomy 7, and mutations of ASXL1, EZH2 and SRSF2. With a
      median follow-up of 43.9 months, MDS patients, based on either the FAB or WHO
      classification, had a significantly poorer overall survival (OS) if they harbored
      SETBP1 mutation. Further, SETBP1 mutation was an independent poor prognostic
      factor for OS (HR = 1.842, CI 95%, 1.1018-3.332, P = 0.043) irrespective of age,
      sex, and the International Prognostic Scoring System. Sequential analysis showed
      that the original SETBP1 mutations in the eight SETBP1-mutated patients studied
      were retained while two of the 101 SETBP1-wild patients acquired novel SETBP1
      mutations during follow-ups. The SETBP1 mutation is associated with poor
      prognosis in MDS. The mutation can be acquired during the clinical course
      suggesting it may play a role in disease progression.

PMID- 24127064
TI  - Strontium-89 for prostate cancer with bone metastases: the potential of cancer
      control and improvement of overall survival.
AB  - OBJECTIVE: Strontium-89 (Sr-89) has been considered to have a tumoricidal effect
      with minimal adverse events. However, few reports have investigated these effects
      in detail. In this study, we examined the tumoricidal and pain-relief effects of
      Sr-89 on prostate cancer with bone metastasis as well as survival. METHODS: A
      retrospective study was performed involving 31 prostate cancer patients with bone
      metastasis treated with Sr-89. Using PSA as an evaluation criterion of cancer
      control, patients were divided into PSA responder and non-responder groups, and
      the survival rates of these groups were compared. In addition, using the total
      amount of painkillers administered as an evaluation criterion of pain relief,
      patients were divided into pain responder and non-responder groups, and the
      survival rates of these groups were also compared. As secondary investigation
      items, age, PSA (ng/ml), pain site, extent of the disease, the presence or
      absence of castration-resistant prostatic cancer (CRPC), the presence or absence
      of a past medical history of treatment with docetaxel in CRPC cases, Gleason
      Score, hemoglobin (g/dl), platelet (Plt) (/MUl), serum carboxyterminal
      telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l)
      were investigated. RESULTS: Longer survival was expected for the PSA responder
      group than for the PSA non-responder group, and whether the spine was the pain
      site and the presence or absence of CRPC were useful as predictors of this. Plt
      was suggested to be a useful indicator. Furthermore, the survival time was
      significantly longer in the pain responder group than in the pain non-responder
      group, and whether the pain site was present in the spine was considered to be a
      predictor; however, no significant difference was noted in any of the items
      assumed to be biomarkers. CONCLUSIONS: Sr-89 has the potential to control PSA and
      prolong survival. A large-scale prospective study of the therapeutic effect of Sr
      89 is expected.

PMID- 24127065
TI  - GuaLou GuiZhi decoction inhibits LPS-induced microglial cell motility through the
      MAPK signaling pathway.
AB  - Microglial activation plays an important role in neroinflammation following
      ischemic stroke. Activated microglial cells can then migrate to the site of
      injury to proliferate and release substances which induce secondary brain damage.
      It has been shown that microglial migration is associated with the activation of
      the mitogen-activated protein kinase (MAPK) signaling pathways. The Chinese
      formula, GuaLou GuiZhi decoction (GLGZD), has long been administered in clinical
      practice for the treatment of post-stroke disabilities, such as muscular
      spasticity. In a previous study, we demonstrated that the anti-inflammtory
      effects of GLGZD were mediated by the TLR4/NF-kappaB pathway in
      lipopolysaccharide (LPS)-stimulated microglial cells. Therefore, in this study,
      we evaluated the role of GLGZD in microglial migration by performing scratch
      wound assays and migration assays. We wished to elucidate the cellular and
      molecular mechanisms elicited by this TCM formula in microglial-induced
      inflammation by evaluating the release and expression of chemotactic cytokines
      [monocyte chemo-attractant protein-1 (MCP-1), macrophage inflammatory protein
      1alpha (MIP-1alpha) and interleukin (IL)-8] by ELISA and quantitative PCR. Our
      results revealed that the migration of microglial cells was enhanced in the
      presence of LPS (100 ng/ml); however, GLGZD (100 ug/ml) significantly inhibited
      cell motility and the production of chemokines through the inhibition of the
      activation of the p38 and c-Jun N-terminal protein kinase (JNK) signaling
      pathway. We demonstrate the potential of GLGZD in the modulation of microglial
      motility by investigating the effects of GLGZD on microglial migration induced by
      LPS. Taken together, our data suggest that GLGZD per se cannot trigger microglial
      motility, whereas GLGZD impedes LPS-induced microglial migration through the
      activation of the MAPK signaling pathway. These results provide further evidence
      of the anti-inflammatory effects of GLGZD and its potential for use in the
      treatment of ischemic stroke. 

PMID- 24127066
TI  - Succinic acid production from corn stalk hydrolysate in an E. coli mutant
      generated by atmospheric and room-temperature plasmas and metabolic evolution
      strategies.
AB  - AFP111 is a spontaneous mutant of Escherichia coli with mutations in the glucose
      specific phosphotransferase system, pyruvate formate lyase system, and
      fermentative lactate dehydrogenase system, created to reduce byproduct formation
      and increase succinic acid accumulation. In AFP111, conversion of xylose to
      succinic acid only generates 1.67 ATP per xylose, but requires 2.67 ATP for
      xylose metabolism. Therefore, the ATP produced is not adequate to accomplish the
      conversion of xylose to succinic acid in chemically defined medium. An E. coli
      mutant was obtained by atmospheric and room-temperature plasmas and metabolic
      evolution strategies, which had the ability to use xylose and improve the
      capacity of cell growth. The concentration of ATP in the mutant was 1.33-fold
      higher than that in AFP111 during xylose fermentation. In addition, under
      anaerobic fermentation with almost 80 % xylose from corn stalk hydrolysate, a
      succinic acid concentration of 21.1 g l(-1) was obtained, with a corresponding
      yield of 76 %. 

PMID- 24127067
TI  - Activating the expression of bacterial cryptic genes by rpoB mutations in RNA
      polymerase or by rare earth elements.
AB  - Since bacteria were found to contain genes encoding enzymes that synthesize a
      plethora of potential secondary metabolites, interest has grown in the activation
      of these cryptic pathways. Homologous and heterologous expression of these
      cryptic secondary metabolite-biosynthetic genes, often "silent" under ordinary
      laboratory fermentation conditions, may lead to the discovery of novel secondary
      metabolites. We review current progress on this topic, describing concepts for
      activating silent genes. We especially focus on genetic manipulation of
      transcription and translation, as well as the utilization of rare earth elements
      as a novel method to activate the silent genes. The possible roles of silent
      genes in bacterial physiology are also discussed. 

PMID- 24127068
TI  - Actinomycetes biosynthetic potential: how to bridge in silico and in vivo?
AB  - Actinomycetes genome sequencing and bioinformatic analyses revealed a large
      number of "cryptic" gene clusters coding for secondary metabolism. These gene
      clusters have the potential to increase the chemical diversity of natural
      products. Indeed, reexamination of well-characterized actinomycetes strains
      revealed a variety of hidden treasures. Growing information about this metabolic
      diversity has promoted further development of strategies to discover novel
      biologically active compounds produced by actinomycetes. This new task for
      actinomycetes genetics requires the development and use of new approaches and
      tools. Application of synthetic biology approaches led to the development of a
      set of strategies and tools to satisfy these new requirements. In this review, we
      discuss strategies and methods to discover small molecules produced by these
      fascinating bacteria and also discuss a variety of genetic instruments and
      regulatory elements used to activate secondary metabolism cryptic genes for the
      overproduction of these metabolites. 

PMID- 24127070
TI  - DNA assembly techniques for next-generation combinatorial biosynthesis of natural
      products.
AB  - Natural product scaffolds remain important leads for pharmaceutical development.
      However, transforming a natural product into a drug entity often requires
      derivatization to enhance the compound's therapeutic properties. A powerful
      method by which to perform this derivatization is combinatorial biosynthesis, the
      manipulation of the genes in the corresponding pathway to divert synthesis
      towards novel derivatives. While these manipulations have traditionally been
      carried out via restriction digestion/ligation-based cloning, the shortcomings of
      such techniques limit their throughput and thus the scope of corresponding
      combinatorial biosynthesis experiments. In the burgeoning field of synthetic
      biology, the demand for facile DNA assembly techniques has promoted the
      development of a host of novel DNA assembly strategies. Here we describe the
      advantages of these recently developed tools for rapid, efficient synthesis of
      large DNA constructs. We also discuss their potential to facilitate the
      simultaneous assembly of complete libraries of natural product biosynthetic
      pathways, ushering in the next generation of combinatorial biosynthesis. 

PMID- 24127069
TI  - Merging chemical ecology with bacterial genome mining for secondary metabolite
      discovery.
AB  - The integration of chemical ecology and bacterial genome mining can enhance the
      discovery of structurally diverse natural products in functional contexts. By
      examining bacterial secondary metabolism in the framework of its ecological
      niche, insights into the upregulation of orphan biosynthetic pathways and the
      enhancement of the enzyme substrate supply can be obtained, leading to the
      discovery of new secondary metabolic pathways that would otherwise be silent or
      undetected under typical laboratory cultivation conditions. Access to these new
      natural products (i.e., the chemotypes) facilitates experimental genotype-to
      phenotype linkages. Here, we describe certain functional natural products
      produced by Xenorhabdus and Photorhabdus bacteria with experimentally linked
      biosynthetic gene clusters as illustrative examples of the synergy between
      chemical ecology and bacterial genome mining in connecting genotypes to
      phenotypes through chemotype characterization. These Gammaproteobacteria share a
      mutualistic relationship with nematodes and a pathogenic relationship with
      insects and, in select cases, humans. The natural products encoded by these
      bacteria distinguish their interactions with their animal hosts and other
      microorganisms in their multipartite symbiotic lifestyles. Though both genera
      have similar lifestyles, their genetic, chemical, and physiological attributes
      are distinct. Both undergo phenotypic variation and produce a profuse number of
      bioactive secondary metabolites. We provide further detail in the context of
      regulation, production, processing, and function for these genetically encoded
      small molecules with respect to their roles in mutualism and pathogenicity. These
      collective insights more widely promote the discovery of atypical orphan
      biosynthetic pathways encoding novel small molecules in symbiotic systems, which
      could open up new avenues for investigating and exploiting microbial chemical
      signaling in host-bacteria interactions. 

PMID- 24127071
TI  - Associations between PTPN2 polymorphisms and susceptibility to ulcerative colitis
      and Crohn's disease: a meta-analysis.
AB  - OBJECTIVE: Ulcerative colitis (UC) and Crohn's disease (CD) result from an
      interaction between genetic and environmental factors. Though several
      polymorphisms have been identified in PTPN2, their roles in the incidence of UC
      and CD are conflicting. This meta-analysis was aimed to clarify the impact of
      these polymorphisms on UC and CD risk. METHOD: PubMed, EMBASE, Cochrane Library
      and CBM were searched until 23 July 2013 for eligible studies on three PTPN2
      polymorphisms: rs2542151, rs1893217 and rs7234029. Data were extracted, and
      pooled odd ratios (ORs) as well as 95 % confidence intervals (95 % CIs) were
      calculated. CONCLUSION: The meta-analysis indicated that rs2542151, rs1893217 and
      rs1893217 were associated with increased CD risk, while the former was associated
      with increased UC risk. The differences in age of onset and ethnic groups may
      influence the associations. Gene-gene and gene-environment interactions should be
      investigated in the future. RESULTS: Seventeen studies with 18,308 cases and
      20,406 controls were included. Significant associations were found between
      rs2542151 polymorphism and CD susceptibility (OR = 1.22, 95 % CI, 1.15-1.30, I
      (2) = 32 %), as well as between rs2542151 and UC susceptibility (OR = 1.16, 95 %
      CI, 1.07-1.25, I (2) = 39 %). A similar result was found in Caucasians, but not
      in Asians. Moreover, a significant increase in CD risk for all carriers of the
      minor allele of rs1893217 (OR = 1.45, 95 % CI, 1.23-1.70, I (2) = 0 %) and
      rs7234029 (OR = 1.36, 95 % CI, 1.16-1.59, I (2) = 0 %) were found. For children,
      the rs1893217 polymorphism appeared to confer susceptibility to CD (OR = 1.56, 95
      % CI, 1.28-1.89, I (2) = 0 %).

PMID- 24127072
TI  - Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated
      RAW 264.7 cells.
AB  - OBJECTIVES AND DESIGN: Chlorogenic acid, which belongs to the polyphenols, is an
      anti-oxidant and anti-obesity agent. In this study, we investigated the role of
      chlorogenic acid in inflammation. MATERIALS AND METHODS: Anti-inflammatory
      effects of chlorogenic acid were examined in lipopolysaccharide (LPS)-stimulated
      murine RAW 264.7 macrophages and BV2 microglial cells. We observed the level of
      various inflammation markers such as nitric oxide (NO), inducible NO synthase
      (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and chemokine (C-X-C motif)
      ligand 1 (CXCL1) under LPS treatment with or without chlorogenic acid. To clarify
      the specific effect of chlorogenic acid, we evaluated the adhesion activity of
      macrophages and ninjurin1 (Ninj1) expression level in macrophages. Finally, we
      confirmed the activation of the nuclear factor-kappaB (NF-kappaB) signaling
      pathway, which is one of the most important transcription factors in the
      inflammatory process. RESULTS: Chlorogenic acid significantly inhibited not only
      NO production but also the expression of COX-2 and iNOS, without any
      cytotoxicity. Chlorogenic acid also attenuated pro-inflammatory cytokines
      (including IL-1beta and TNF-alpha) and other inflammation-related markers such as
      IL-6 in a dose-dependent manner. Additionally, endotoxin-induced adhesion of
      macrophages and the expression level of ninjurin1 (Ninj1) were decreased by
      chlorogenic acid. Finally, chlorogenic acid inhibited the nuclear translocation
      of NF-kappaB. CONCLUSIONS: Chlorogenic acid may be beneficial for the prevention
      and treatment of anti-inflammatory diseases.

PMID- 24127073
TI  - A 1,100-year-old founder effect mutation in IL12B gene is responsible for
      Mendelian susceptibility to mycobacterial disease in Tunisian patients.
AB  - Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder
      predisposing apparently healthy individuals to infections caused by weakly
      virulent mycobacteria such as bacille Calmette-Guerin (BCG), environmental
      mycobacteria, and poorly virulent Salmonella strains. IL-12p40 deficiency is the
      first reported human disease due to a cytokine gene defect and is one of the
      deficiencies that cause MSMD. Nine mutant alleles only have been identified in
      the IL12B gene, and three of them are recurrent mutations due to a founder effect
      in specific populations. IL-12p40 deficiency has been identified especially in
      countries where consanguinity is high and where BCG vaccination at birth is
      universal. We investigated, in such settings, the clinical, cellular, and
      molecular features of six IL-12p40-deficient Tunisian patients having the same
      mutation in IL12B gene (c.298_305del). We found that this mutation is inherited
      as a common founder mutation arousing ~1,100 years ago. This finding facilitates
      the development of a preventive approach by genetic counseling and prenatal
      diagnosis especially in affected families. 

PMID- 24127075
TI  - Localised corrosion in aluminium alloy 2024-T3 using in situ TEM.
AB  - An approach to carry out chemical reactions using aggressive gases in situ in a
      transmission electron microscope (TEM), at ambient pressures of 1.5 bar using a
      windowed environmental cell, called a nanoreactor, is presented here. The
      nanoreactor coupled with a specially developed holder with platinum tubing
      permits the usage of aggressive chemicals like hydrochloric acid (HCl). 

PMID- 24127074
TI  - The opposite prognostic significance of nuclear and cytoplasmic p21 expression in
      resectable gastric cancer patients.
AB  - BACKGROUND: Protein p21(Cip1/Waf1) is a cyclin-dependent kinase inhibitor, which
      plays important roles in cell cycle arrest, senescence, and apoptosis.
      Interestingly, the nuclear and cytoplasmic p21 executes various functions in the
      cell. In this study, we investigated the prognostic impact of subcellular p21
      expression in gastric cancer (GC). METHODS: Expressions of subcellular p21 was
      assessed by immunohistochemistry using a tissue microarray in a training cohort
      and it went into a second testing cohort and finally to a validating cohort.
      Prognostic and predictive role of subcellular p21 expression status was
      evaluated. We also studied the roles of subcellular p21 in GC cell migration and
      invasion. RESULTS: Nuclear and cytoplasmic p21 protein levels were significantly
      reduced and increased in GC lesions compared with adjacent non-cancerous tissues,
      respectively. Low nuclear p21 or high cytoplasmic p21 expression significantly
      correlated with shorter overall survival (OS), as well as with clinicopathologic
      characteristics in patients. Multivariate regression analysis showed that low
      nuclear and high cytoplasmic p21 expression, separately and together, were
      independent negative markers of OS. Finally, we found that nuclear p21 inhibits
      but cytoplasmic p21 promotes cell migration and invasion abilities. CONCLUSIONS:
      These findings suggest that nuclear and cytoplasmic p21 protein expression in
      tumor are novel candidate prognostic markers in resectable human gastric
      carcinoma, and they exert distinct roles in cell migration and invasion.

PMID- 24127076
TI  - [Spinal injuries in children and adolescents].
AB  - Pediatric cervical spine injuries are rare. Knowledge of possible types of
      injury, physiological development and anomalies is necessary in order to not
      overlook the injury and to initiate suitable therapy. Description of the clinical
      assessment, Management of diagnostics and therapy of specific injuries. Based on
      a selective literature search and taking into consideration our own experience,
      typical injuries at the upper and lower cervical spine in pediatric patients are
      depicted. In the presence of neurological deficits, identification of the cause
      is crucial. Odontoid fractures and injuries to the second cervical vertebra are
      common in upper cervical spine injuries, compression fractures and facet joint
      dislocation injuries are common in lower cervical spine injuries. Depending on
      the location of the injury and on the grade of instability, specific therapy,
      including conservative treatment (orthosis, halo fixation) and operative
      treatment (internal fixation, fusion) might be necessary. 

PMID- 24127077
TI  - [Postoperative implant-associated osteomyelitis of the shoulder: Hardware
      retaining revision concept using temporary drainage].
AB  - BACKGROUND: Posttraumatic and postoperative osteomyelitis (PPO) is a subgroup of
      bone infections with increasing importance. However, to date no standardized
      reoperation concept exists particularly for patients with PPO of the shoulder
      region. Therefore the purpose of this study was to evaluate a revision concept
      including debridement, irrigation, and insertion of temporary drainage with
      hardware retention until healing. PATIENTS AND METHODS: A total of 31 patients
      with PPO were included with a proximal humerus fracture (n = 14), clavicle
      fracture (n = 10), or AC-joint separation (n = 7). In all, 27 of these patients
      could be followed for > 1 year. RESULTS: Hardware retention until fracture or
      ligament healing could be achieved in > 83%. Six patients required follow-up
      debridement due to recurrent infections, but then were unremarkable. Clinical
      outcome showed excellent Constant scores (91.6 +/- 2.8). CONCLUSION: A cost
      efficient, simple, and successful revision concept for patients with PPO of the
      shoulder region is described.

PMID- 24127078
TI  - Socioeconomic driving factors of nitrogen load from food consumption and
      preventive measures.
AB  - To diagnose environmental nitrogen (N) load from food consumption and to suggest
      preventive measures, this study identified relationships between nitrogen load
      from food consumption and driving factors by examining six representative
      countries and regions for the period 1970-2009 as an example. The logarithmic
      mean Divisia index technique was used to disassemble nitrogen load growth into
      four driving factors: population, economic activity, food intensity of the
      economy, and nitrogen content of food. In all study areas, increased economic
      activity was the main factor driving nitrogen load increase. The positive effect
      of population growth was relatively small but not negligible and changes in food
      intensity had a decreasing effect on nitrogen load. Changes in nitrogen content
      of food varied between areas. Broad strategies to reduce and mitigate nitrogen
      loading and decouple nitrogen load from economic growth in both developed and
      developing countries are suggested. 

PMID- 24127079
TI  - The Brazilian Unified National Health System 25 years later.

PMID- 24127080
TI  - The crisis of health workforce.

PMID- 24127081
TI  - [The Citizen Constitution and the 25th anniversary of the Brazilian Unified
      National Health System (SUS)].
AB  - This article, celebrating the 25th anniversary of Brazil's 1988 Constitution,
      aims to review the country's social policy development, discuss political
      projects, and analyze challenges for the sustainability of the Unified National
      Health System (SUS). Based on public policymaking studies, the article revisits
      the origins of liberal social policy, focused on social assistance, and analyzes
      the hegemony of U.S. policies targeting poverty and their repercussions for
      universal policies. After identifying the formulation of political projects in
      Brazil's democratic transition, it discusses their implications during the
      various Administrations since 1988, along with the difficulties faced by the
      National Health System. The article concludes that the political forces occupying
      government in the last two decades have failed to present a project for the
      country on the same level as those who drafted the Citizen Constitution. 

PMID- 24127082
TI  - [Debate on the paper by Paim].

PMID- 24127083
TI  - [Health reform enforcement through social participation].

PMID- 24127084
TI  - [Shelf life of SUS Health System].

PMID- 24127085
TI  - [Long days last a hundred years].

PMID- 24127086
TI  - [The 25th anniversary of SUS Health System: disenchantment or opportunity?].

PMID- 24127087
TI  - [Criticism, history and the country we want: comments on Paim's article].

PMID- 24127088
TI  - [Nostalgia for the future or a health system in democratic times].

PMID- 24127089
TI  - [Trends on social and health politics in Brazil after 1988].

PMID- 24127090
TI  - [The author replies].

PMID- 24127091
TI  - Possibilities and challenges for physical and social environment research in
      Brazil: a systematic literature review on health behaviors.
AB  - This systematic review analyzed articles focused on the relationship between
      environment (physical, built, perceived, and social) and smoking, alcohol
      drinking, physical activity, diet, and obesity in Brazil. Studies published
      between 19952011 were retrieved from seven databases and hand searches. Based on
      the 42 articles reviewed, gaps were identified and recommendations were made for
      future research. Despite a growing number of studies, the Brazilian literature is
      still limited. The increase of articles in 2010-2011 coincided with the
      diversification of lifestyles studied, although physical activity domain remains
      predominant. Most studies analyzed neighborhood settings and used subjective
      measures for lifestyle and for environment. The presence of recreational
      facilities was the main physical environment aspect studied, while safety from
      crime was the prominent social environment factor. More research is needed to
      yield a rich body of evidence that leads to theoretical and methodological
      advances, and that supports interventions aimed at creating healthy environments.

PMID- 24127092
TI  - [Factors associated with Brucella canis seropositivity in kennels of two regions
      of Antioquia, Colombia].
AB  - The objectives of this study were to determine Brucella canis seroprevalence in
      dogs and in humans living near kennels and to explore risk factors associated
      with seropositivity. Twenty kennels were included in a serological survey with
      RSAT-2ME, and samples were collected from 428 dogs and 91 humans. An interview
      was applied to determine risk factors, and the data were analyzed using logistic
      regression. Seroprevalence was 15% in dogs and 9% in humans. Factors associated
      with current canine seropositivity were: history of canine seropositivity, non
      culling of seropositive dogs, history of abortion, poor hygiene and personal
      protection during reproductive service, and unsafe procedures during care for
      abortions. Protective factors included: rural location of kennels, ease of
      cleaning kennels, pre-mating RSAT-2ME, and safe procedures during care for
      delivery. Factors associated with seropositive status in humans were: kennels
      located in Valle de Aburra and urban location. 

PMID- 24127093
TI  - Built environment and social environment: associations with overweight and
      obesity in a sample of Brazilian adults.
AB  - The aim of this study was to assess associations between the built environment
      and social environment and excess weight in an urban population. Participants
      were selected from the Surveillance System for Risk Factors for Chronic Diseases
      (VIGITEL). The study used data from the city of Belo Horizonte, Minas Gerais
      State, Brazil. A total of 3,425 interviews from the years 2008 and 2009 were
      used. Georeferenced data on parks, squares, and locations for physical exercise,
      population density, and food stores were used to assess the built environment.
      Description of the social environment used income and homicide rate for the
      neighborhood. Environmental variables associated independently with excess weight
      were population density, presence of parks, squares, and locations for physical
      exercise, and self-reported presence of locations for physical exercise. The
      findings show that residential neighborhood characteristics are associated with
      excess weight in urban adults. 

PMID- 24127094
TI  - [Processes in the construction of the Brazilian National Health Promotion
      Policy].
AB  - We investigated the processes involved in the construction of the Brazilian
      National Health Promotion Policy (PNPS) through the analysis of three documents
      produced by the Ministry of Health from 2002 to 2005 and the final text of the
      National Health Promotion Policy, approved in 2006. We interviewed five subjects
      who participated in drafting the PNPS, three of whom were Ministry of Health
      administrators, plus two researchers. The documents were explored with discourse
      analysis. The article contributes to the debate on the development of the PNPS.
      Health promotion showed various points of disagreement, which led to the delay in
      the document's final approval. International induction via funding proved to be a
      crucial element for defining the final wording of the PNPS, reestablishing the
      emphasis (subject to criticism) on lifestyle changes in its "Actions". The
      article highlights the negotiated consensus that led to the creation of the PNPS
      Management Committee, with participation by various sub-sectors, an innovative
      structure within the Ministry of Health. 

PMID- 24127095
TI  - [Prevalence of blood donation and associated factors in Florianopolis, Southern
      Brazil: a population-based study].
AB  - The main objectives of this study were to estimate the prevalence of blood
      donation and to identify associated factors. A populated-based cross-sectional
      study was carried out (n = 1,720) including subjects 20 to 59 years of age in
      Florianopolis, Santa Catarina State, Brazil. Blood donation any time in life and
      in the previous year was reported by 30.6% and 6.2% of respondents, respectively.
      Among the latter, 31.8% reported repeat donation (at least twice in the previous
      year), 80.4% reported voluntary donation, and 15.9% replacement donation.
      Multivariate Poisson regression (p < 0.05) showed that male gender, black or
      brown self-reported skin color, higher age group, higher educational level, and
      living with other blood donors were all associated with ever donating blood,
      whereas younger age, single marital status, and higher educational level were
      associated with donating in the previous year. We found higher prevalence of
      blood donation in the previous year and higher percentage of young donors in this
      group, as well as lower percentage of replacement donors than previously reported
      in Brazil. 

PMID- 24127096
TI  - Living conditions and access to health services by Bolivian immigrants in the
      city of Sao Paulo, Brazil.
AB  - Bolivian immigrants in Brazil experience serious social problems: precarious work
      conditions, lack of documents and insufficient access to health services. The
      study aimed to investigate inequalities in living conditions and access to health
      services among Bolivian immigrants living in the central area of Sao Paulo,
      Brazil, using a cross-sectional design and semi-structured interviews with 183
      adults. According to the data, the immigrants tend to remain in Brazil, thus
      resulting in an aging process in the group. Per capita income increases the
      longer the immigrants stay in the country. The majority have secondary schooling.
      Work status does not vary according to time since arrival in Brazil. The
      immigrants work and live in garment sweatshops and speak their original
      languages. Social networks are based on ties with family and friends. Access to
      health services shows increasing inclusion in primary care. The authors conclude
      that the immigrants' social exclusion is decreasing due to greater access to
      documentation, work (although precarious), and the supply of health services from
      the public primary care system. 

PMID- 24127097
TI  - [Contributions by integrative community therapy to users of Psychosocial Care
      Centers (CAPS) and family members: thematic oral history].
AB  - The aim of this study was to analyze contributions by integrative community
      therapy to behavior changes in users of Psychosocial Care Centers (CAPS). This
      was a comprehensive-interpretative study with a qualitative approach, based on
      thematic oral history. The study site was the Caminhar Center in Joao Pessoa,
      Paraiba State, Brazil. The study material was produced with interviews conducted
      with six subjects and was discussed using thematic analysis as proposed by
      Minayo, providing the basis for two major thematic lines: integrative community
      therapy as a liberating praxis and changes that make the difference. The
      subjects' stories revealed significant changes in the personal, professional, and
      community fields, based on their inclusion in the integrative community therapy
      circles, a strategy that promoted the recovery of processes of natural
      socialization that constitute human life. The use of integrative community
      therapy was clearly related to proposals for the participants' psychosocial
      integration and rehabilitation. 

PMID- 24127098
TI  - [Self-efficacy and physical activity in adolescents in Curitiba, Parana State,
      Brazil].
AB  - This study aimed to examine the association between physical activity and self
      efficacy in adolescents. A school-based survey was conducted with 1,698
      adolescents from Curitiba, Parana State, Brazil. Physical activity was evaluated
      as weekly frequency (days per week) of moderate or vigorous physical activity.
      Self-efficacy was analyzed as the sum of a 10-item scale. The association between
      self-efficacy and physical activity was tested by Poisson regression (p < 0.05),
      stratified by gender. Among boys, only high self-efficacy was associated with all
      categories of physical activity (p < 0.001), while for girls moderate and high
      levels of self-efficacy were associated with all categories of physical activity
      (p < 0.001). In conclusion, self-efficacy showed a positive association with
      physical activity in adolescents, although the relationship was more consistent
      in girls. The finding is important for designing interventions to promote
      physical activity in this age group. 

PMID- 24127099
TI  - Representations of nurses regarding sexuality of women treated for breast cancer
      in Brazil.
AB  - The development of new treatments has improved survival and quality of life among
      cancer patients. Nurses are expected to answer questions and to provide
      orientation regarding patients' sexuality since it is an important aspect of
      life. The main objective of this paper is to understand the representations of
      sexuality among nurses working with women who survive breast cancer after
      diagnosis and during treatment assuming that their representations may affect
      communication with the patient. This is a qualitative study using an in-depth
      guideline which involved interviews with 28 nurses living and working in the
      southeast of Brazil. The narratives were submitted to a content analysis and
      categories of representations were identified and are discussed here. Several
      representations of sexuality were found in the nurses' discourses. Some of the
      nurses' representations may be expected to hinder their ability to provide
      helpful orientation regarding the sexual lives of these patients. 

PMID- 24127100
TI  - [A Bayesian model to investigate excess mortality during the dengue epidemic in
      Greater Metropolitan Rio de Janeiro, Brazil, in 2007-2008].
AB  - The aim of this study was to investigate excess mortality from dengue in Greater
      Metropolitan Rio de Janeiro, Brazil, during an epidemic in 2007-2008. A Poisson
      dynamic model was tested to predict the number of deaths during these epidemic
      years. Inference was conducted with a Bayesian approach. Excess mortality was
      detected in March 2008 in children < 15 years. In addition, the highest number of
      reported dengue cases in Rio de Janeiro was in March and April 2008. Since the
      increase in mortality should be preceded by an increase in morbidity, one can
      hypothesize that there was excess mortality from dengue in children during the
      epidemic in Greater Metropolitan Rio de Janeiro in March 2008. 

PMID- 24127101
TI  - The Appraisal of Self-Care Agency Scale - Revised (ASAS-R): adaptation and
      construct validity in the Brazilian context.
AB  - This study presents the psychometric properties of the Brazilian version of the
      Appraisal of Self-Care Agency Scale - Revised (ASAS-R). The sample was made up of
      627 subjects (69.8% women) aged between 18 and 88 years (mean = 38.3; SD = 13.26)
      from 17 Brazilian states. Exploratory factor analysis of part of the sample (n1 =
      200) yielded a three-factor solution which showed adequate levels of reliability.
      Two confirmatory factor analyses of the other part of the sample (n2 = 427)
      tested both the exploratory and the original model. The analysis of convergent
      validity using the Subjective Happiness Scale, the Satisfaction with Life Scale,
      and the 36-item Short Form Health Survey Version 2 (SF-36v2) demonstrated
      adequate levels of validity. A significant correlation was found between levels
      of self-care agency and age, level of education and income. The analysis of
      sample members with chronic disease (n = 134) showed that higher levels of self
      care agency indicated lower levels of negative impact of the chronic illness in
      the individual's everyday life. 

PMID- 24127102
TI  - [Folic acid intake before and after mandatory fortification: a population-based
      study in Sao Paulo, Brazil].
AB  - This study analyzed folic acid intake before and since mandatory fortification.
      Dietary data were collected by 24-hour recall in a health survey in Sao Paulo
      (ISA-Capital) in 2003 and 2007-2008, stratifying the population according to life
      stage and gender. Estimated average requirement (EAR) and tolerable upper intake
      level (UL) were used to assess intake. Prevalence of inadequate folic acid intake
      decreased in all groups, especially adolescents and adult males (72% to < 1% and
      76% to 6%, respectively) but remained high in adult women (38%). Beans were the
      main source of folic acid before fortification. With fortification, bread became
      the main source, but beans remained important. Fortification was successful
      (increased intake within safe levels), but it raised concerns about the high
      proportion in the target group (adult women) who still fail to meet the
      recommended intake.

PMID- 24127103
TI  - [A systematic social observation tool: methods and results of inter-rater
      reliability].
AB  - Systematic social observation has been used as a health research methodology for
      collecting information from the neighborhood physical and social environment. The
      objectives of this article were to describe the operationalization of direct
      observation of the physical and social environment in urban areas and to evaluate
      the instrument's reliability. The systematic social observation instrument was
      designed to collect information in several domains. A total of 1,306 street
      segments belonging to 149 different neighborhoods in Belo Horizonte, Minas
      Gerais, Brazil, were observed. For the reliability study, 149 segments (1 per
      neighborhood) were re-audited, and Fleiss kappa was used to access inter-rater
      agreement. Mean agreement was 0.57 (SD = 0.24); 53% had substantial or almost
      perfect agreement, and 20.4%, moderate agreement. The instrument appears to be
      appropriate for observing neighborhood characteristics that are not time
      dependent, especially urban services, property characterization, pedestrian
      environment, and security. 

PMID- 24127104
TI  - [Evaluating the implementation of Information System on Live Births in
      municipalities of Minas Gerais, Brazil].
AB  - This study evaluated the degree of implementation of the Information System on
      Live Births (SINASC) and its relationship to the organizational context in
      municipalities (counties) of Minas Gerais State, Brazil, in 2010. The sample
      included 132 municipalities that had healthcare facilities providing childbirth
      care and the decentralized SINASC. Data collection used a semi-structured
      questionnaire. Degree of implementation was defined by a scoring system with
      different weights for each indicator, according to the respective levels of
      importance assigned to them, using the following classification: adequate,
      inadequate, and critical. Data analysis used the median as the summary measure
      and the Pearson chi-square test for comparison of proportions. SINASC is not
      adequately implemented in the majority of the municipalities in the sample.
      Population size and quality of the municipal administration did not influence the
      degree of implementation. In terms of organization of information in the SINASC,
      the structure was evaluated as better than the process. Limitations included lack
      of qualified staff, unsatisfactory collection and completion of certificates of
      live birth, underutilization of data, and limited publication of the information.

PMID- 24127105
TI  - Physical activity indicators in adults from a state capital in the South of
      Brazil: a comparison between telephone and face-to-face surveys.
AB  - The aim of this study was to compare estimates of prevalence of physical activity
      indicators and associated sociodemographic factors obtained from telephone and
      face-to-face interviews with adults. Data from a cross-sectional populationbased
      survey of adults living in Florianopolis, Santa Catarina State, Brazil was
      compared to data collected through the telephonic system VIGITEL. There was no
      significant difference between the results from telephone interviews (n = 1,475)
      and face-to-face interviews (n = 1,720) with respect to prevalence of sufficient
      leisure time physical activity (19.3% versus 15.5%, respectively), sufficient
      leisure time and/or commuting physical activity (35.1% versus 29.1%,
      respectively) and physical inactivity (16.2% versus 12.6%, respectively). Some
      differences were observed with respect to the sociodemographic factors associated
      with leisure time and/or commuting physical activity and physical inactivity. The
      two techniques yielded generally similar results with respect to prevalence and
      sociodemographic factors associated to physical activity indicators. 

PMID- 24127106
TI  - [Epidemiological characteristics of AIDS cases in persons aged 60 years or older,
      Pernambuco State, Brazil, 1998 to 2008].
AB  - Changes have occurred in the world scenario in recent years due to declining
      fertility and mortality, and longevity has thus appeared as a real phenomenon.
      Sexuality of the elderly is viewed with various prejudices. The current study
      characterized AIDS cases in persons 60 years or older in Pernambuco State,
      Brazil, reported to the State Health Department from January 1, 1998, to December
      31, 2008. A cross-sectional descriptive study was performed with data from the
      Information System on Diseases of Notification (SINAN). In 1998 the AIDS
      incidence rate in the target age bracket was 1.6 cases per 100 thousand,
      increasing to 4.8 per 100 thousand in 2008, or an increase of 200%. There is thus
      an evident need to develop measures for prevention, diagnosis, and patient care
      specifically targeting the elderly, since sexuality in this age bracket is still
      enshrouded by myths and taboos. 

PMID- 24127107
TI  - Relative effectiveness of dominant versus non-dominant hand position for
      rescuer's side of approach during chest compressions between right-handed and
      left-handed novice rescuers.
AB  - INTRODUCTION: The major components affecting high quality cardiopulmonary
      resuscitation (CPR) have been defined as the ability of the rescuer, hand
      position, position of the rescuer and victim, depth and rate of chest
      compressions, and fatigue. Until now, there have been no studies on dominant
      versus non-dominant hand position and the rescuer's side of approach. This study
      was designed to evaluate the effectiveness of hand position and approach side on
      the quality of CPR between right-handed (RH) and left-handed (LH) novice
      rescuers. MATERIAL AND METHODS: 44 health science university students with no
      previous experience of basic life support (BLS) volunteered for the study. We
      divided volunteers into two groups by handedness. Adult BLS was performed on a
      manikin for 2 min in each session. The sequences were randomly performed on the
      manikin's left side of approach (Lap) with the rescuer's left hand in contact
      with the sternum (Lst), Lap/Rst, Rap/Lst and Rap/Rst. RESULTS: We compared the
      quality of chest compressions between the RH and LH groups according to
      predetermined positions. A significant decrease in mean compression depth between
      the two groups was only observed when rescuers performed in the Rap/Lst scenario,
      regardless of hand dominance. The frequency of correct hand placement also
      significantly decreased in the Lap/Rst position for the LH group. CONCLUSIONS:
      The performance of novice rescuers during chest compressions is influenced by the
      position of the dominant hand and the rescuer's side of approach. In CPR training
      and real world situations, a novice rescuer, regardless of handedness, should
      consider hand positions for contacting the sternum identical to the side of
      approach after approaching from the nearest and most accessible side, for optimal
      CPR performance.

PMID- 24127108
TI  - Internet usage and knowledge of radiation health effects and preventive
      behaviours among workers in Fukushima after the Fukushima Daiichi nuclear power
      plant accident.
AB  - BACKGROUND: The Fukushima Daiichi nuclear power plant accident (FDNPPA) was the
      world's second largest nuclear power plant accident. At the time that it
      occurred, internet usage prevalence in Japan was as high as 80%. OBJECTIVES: To
      compare health knowledge on radiation and preventive behaviour between internet
      users and non-users among adults employed in industries in Fukushima after the
      nuclear disaster. METHODS: We conducted a cross-sectional questionnaire study
      among adults employed in industries in Fukushima 3-5 months after the FDNPPA.
      Targets were 1394 regular workers who took part in health seminars provided by
      the Fukushima Occupational Health Promotion Center. After applying the selection
      criteria, there were 1119 eligible participants. The questionnaire asked for
      personal characteristics and main sources of information about the FDNPPA, as
      well as health knowledge on radiation and preventive behaviours following the
      nuclear accident. We assessed the contribution of each variable using logistic
      regression analysis. RESULTS: Among the eligible respondents, 637 workers (56.9%)
      were internet users and 482 (43.1%) were non-users. Internet users had more
      health knowledge than non-users (average 4.6 radiation-related health conditions
      in internet users vs 3.6 conditions in non-users) and more preventive behaviours
      (average 2.6 behaviours in internet users vs 1.9 in non-users). According to
      logistic regression analyses, internet usage was positively associated with
      greater health knowledge on radiation (OR 1.13; 95% CI 1.08 to 1.20) and more
      preventive behaviours (OR 1.14; 95% CI 1.07 to 1.23). CONCLUSIONS: Internet usage
      was significantly and positively associated with greater health knowledge and
      more preventive behaviours. The internet is a useful method of distributing
      information to the general public in emergency situations such as a nuclear
      disaster.

PMID- 24127109
TI  - Regulating aging in adult stem cells with microRNA.
AB  - Aging can be defined as the result of accumulated cellular damage and
      deregulation of the epigenome. These changes cause impaired cell maintenance
      systems, reduced tissue regeneration, weakening of the immune system and
      increased risk of malignancy. The higher mortality rate in older individuals is a
      result of these pathologies. The study of age-related changes in adult stem cells
      and their regenerative potential is crucial to our understanding of the physical
      deterioration of organs and tissues. The growing interest and knowledge in the
      field of microRNAs adds a further dimension to this field of research. MicroRNAs
      are important posttranscriptional regulators of gene expression. They co-regulate
      stem cell properties such as potency, differentiation, self-renewal and
      senescence. Various cell systems, e.g. defense mechanisms against reactive oxygen
      radicals (ROS), DNA repair and apoptosis are regulated by microRNAs. These
      properties and the assumption that microRNAs act as some kind of general switch
      make them highly relevant in aging research. 

PMID- 24127110
TI  - [Vaccination in the elderly].
AB  - The aging immune system, so-called immunosenescence, is well documented as the
      cause of increased infection rates and severe, often complicated course of
      infections in the elderly with increased morbidity and mortality rates.
      Furthermore, it can lead to decreased efficacy of vaccination. The administration
      of more immunogenic vaccines can be beneficial in the elderly. Implementing
      vaccination recommendations for the elderly by STIKO can reduce burden of
      infectious diseases by prevention of infection or reduction of severity of
      infection. The following vaccinations are recommended by STIKO for all persons
      aged 60 and above: annual influenza vaccination (additionally all nursing home
      residents independently of age), once only pneumococcal polysaccharide
      vaccination, completion of tetanus and diphtheria (Td) vaccination as well as
      regular revaccination. All adults should be vaccinated against pertussis with
      Tdap vaccine once. Meanwhile, pneumococcal conjugate vaccine is allowed for
      administration in adults but is not recommended by STIKO yet. A lifelong course
      of vaccination may help to attenuate the effect of immunosenescence. 

PMID- 24127112
TI  - [On the death of Professor Thorsten Nikolaus].

PMID- 24127117
TI  - Non-pharmacological interventions for preventing venous insufficiency in a
      standing worker population.
AB  - BACKGROUND: Chronic venous insufficiency (CVI) is a common problem, affecting up
      to 50% of the population in industrialised countries. It is a chronic condition
      which, if untreated, can progress to serious complications that in turn can
      interfere with working ability. Standing at work is a known risk factor for CVI,
      yet the true effect of non-pharmacological preventive strategies remains unknown.
      This is an update of a review first published in 2012. OBJECTIVES: To assess the
      efficacy of non-pharmacological strategies and devices to prevent CVI in a
      standing worker population. SEARCH METHODS: For this update the Cochrane
      Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the
      Specialised Register (last searched September 2013) and CENTRAL (2013, Issue 8).
      We also handsearched reference lists of relevant studies. SELECTION CRITERIA:
      Randomised and non-randomised controlled trials that recruited standing workers
      to evaluate non-pharmacological devices or strategies used to prevent CVI were
      eligible for inclusion. Trials had to report an objective measure of clinical
      features of CVI or complaints associated with this condition in order to be
      included. DATA COLLECTION AND ANALYSIS: Selection of the trials, quality
      assessment and data abstraction were completed independently by two review
      authors. We resolved disagreements by discussion. Only one trial was eligible for
      inclusion in the review so we did not perform meta-analyses. MAIN RESULTS: The
      primary outcomes of this review were clinical features of CVI and its associated
      symptoms. No new included studies were identified for this update. One
      prospective cross-over trial was included in this review. It measured the effect
      of no compression followed by two phases with different gradients of compression
      stockings on symptoms in 19 female flight attendants who were required to stand,
      almost continuously, for long periods of time. The included study provided some
      evidence that compression stockings improved symptoms of leg fatigue in standing
      workers. However, the strength of the evidence in this review is weak as it is
      based on only one very small trial which was at high risk of bias. The included
      study did not address any of the secondary outcomes including quality of life or
      economic impact of the interventions. Nor did the study report the length of time
      that the population were required to stand at work. Furthermore, no trials were
      found which measured the effectiveness of other non-pharmacological interventions
      or strategies aimed at preventing CVI in standing workers. AUTHORS' CONCLUSIONS:
      Due to the extremely limited number of trials, there is insufficient evidence to
      draw any conclusions about the effectiveness of non-pharmacological interventions
      for preventing CVI in standing workers. Further large-scale studies examining all
      possible non-pharmacological interventions and outcomes are required.

PMID- 24127118
TI  - Long-acting beta2-agonists for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease
      that causes progressive symptoms of breathlessness, cough and mucus build-up. It
      is the fourth or fifth most common cause of death worldwide and is associated
      with significant healthcare costs.Inhaled long-acting beta2-agonists (LABAs) are
      widely prescribed to manage the symptoms of COPD when short-acting agents alone
      are no longer sufficient. Twice-daily treatment with an inhaled LABA is aimed at
      relieving symptoms, improving exercise tolerance and quality of life, slowing
      decline and even improving lung function and preventing and treating
      exacerbations. OBJECTIVES: To assess the effects of twice-daily long-acting beta2
      agonists compared with placebo for patients with COPD on the basis of clinically
      important endpoints, primarily quality of life and COPD exacerbations. SEARCH
      METHODS: We searched the Cochrane Airways Group trials register,
      ClinicalTrials.gov and manufacturers' websites in June 2013. SELECTION CRITERIA:
      Parallel, randomised controlled trials (RCTs) recruiting populations of patients
      with chronic obstructive pulmonary disease. Studies were required to be at least
      12 weeks in duration and designed to assess the safety and efficacy of a long
      acting beta2-agonist against placebo. DATA COLLECTION AND ANALYSIS: Data and
      characteristics were extracted independently by two review authors, and each
      study was assessed for potential sources of bias. Data for all outcomes were
      pooled and subgrouped by LABA agent (formoterol 12 MUg, formoterol 24 MUg and
      salmeterol 50 MUg) and then were separately analysed by LABA agent and subgrouped
      by trial duration. Sensitivity analyses were conducted for the proportion of
      participants taking inhaled corticosteroids and for studies with high or uneven
      rates of attrition. MAIN RESULTS: Twenty-six RCTs met the inclusion criteria,
      randomly assigning 14,939 people with COPD to receive twice-daily LABA or
      placebo. Study duration ranged from three months to three years; the median
      duration was six months. Participants were more often male with moderate to
      severe symptoms at randomisation; mean forced expiratory volume in 1 second
      (FEV1) was between 33% and 55% predicted normal in the studies, and mean St
      George's Respiratory Questionnaire score (SGRQ) ranged from 44 to 55 when
      reported.Moderate-quality evidence showed that LABA treatment improved quality of
      life on the SGRQ (mean difference (MD) -2.32, 95% confidence interval (CI) -3.09
      to -1.54; I(2) = 50%; 17 trials including 11,397 people) and reduced the number
      of exacerbations requiring hospitalisation (odds ratio (OR) 0.73, 95% CI 0.56 to
      0.95; I(2) = 10%; seven trials including 3804 people). In absolute terms, 18
      fewer people per 1000 were hospitalised as the result of an exacerbation while
      receiving LABA therapy over a weighted mean of 7 months (95% CI 3 to 31 fewer).
      Scores were also improved on the Chronic Respiratory Disease Questionnaire (CRQ),
      and more people receiving LABA treatment showed clinically important improvement
      of at least four points on the SGRQ.The number of people who had exacerbations
      requiring a course of oral steroids or antibiotics was also lower among those
      taking LABA (52 fewer per 1000 treated over 8 months; 95% CI 24 to 78 fewer,
      moderate quality evidence).Mortality was low, and combined findings of all
      studies showed that LABA therapy did not significantly affect mortality (OR 0.90,
      95% CI 0.75 to 1.08; I(2) = 21%; 23 trials including 14,079 people, moderate
      quality evidence). LABA therapy did not affect the rate of serious adverse events
      (OR 0.97, 95% CI 0.83 to 1.14; I(2) = 34%, moderate quality evidence), although
      there was significant unexplained heterogeneity, especially between the two
      formoterol doses.LABA therapy improved predose FEV1 by 73 mL more than placebo
      (95% CI 48 to 98; I(2) = 71%, low quality evidence), and people were more likely
      to withdraw from placebo than from LABA therapy (OR 0.74, 95% CI 0.69 to 0.80;
      I(2) = 0%). Higher rates of withdrawal in the placebo arm may reduce our
      confidence in some results, but the disparity is more likely to reduce the
      magnitude of difference between LABA and placebo than inflate the true effect;
      removing studies at highest risk of bias on the basis of high and unbalanced
      attrition did not change conclusions for the primary outcomes. AUTHORS'
      CONCLUSIONS: Moderate-quality evidence from 26 studies showed that inhaled long
      acting beta2-agonists are effective over the medium and long term for patients
      with moderate to severe COPD. Their use is associated with improved quality of
      life and reduced exacerbations, including those requiring hospitalisation.
      Overall, findings showed that inhaled LABAs did not significantly reduce
      mortality or serious adverse events.

PMID- 24127119
TI  - Investigation of functionalized alpha-chloroalkyllithiums for a stereospecific
      reagent-controlled homologation approach to the analgesic alkaloid (-)
      epibatidine.
AB  - Four putative functionalized alpha-chloroakyllithiums RCH2CHLiCl, where
      R=CHCH2(18 a), CCH (18 b), CH2OBn (18 c), and CH[O(CH2)2O] (18 d), were generated
      in situ by sulfoxide-lithium exchange from alpha-chlorosulfoxides, and
      investigated for the stereospecific reagent-controlled homologation (StReCH) of
      phenethyl and 2-chloropyrid-5-yl (17) pinacol boronic esters. Deuterium labeling
      experiments revealed that alpha-chloroalkyllithiums are quenched by proton
      transfer from their alpha-chlorosulfoxide precursors and it was established that
      this effect compromises the yield of StReCH reactions. Use of alpha-deuterated
      alpha-chlorosulfoxides was discovered to ameliorate the problem by retarding the
      rate of acid-base chemistry between the carbenoid and its precursor. Carbenoids
      18 a and 18 b showed poor StReCH efficacy, particularly the propargyl group
      bearing carbenoid 18 b, the instability of which was attributed to a facile 1,2
      hydride shift. By contrast, 18 d, a carbenoid that benefits from a stabilizing
      interaction between O and Li atoms gave good StReCH yields. Boronate 17 was chain
      extended by carbenoids 18 a, 18 b, and 18 d in 16, 0, and 68% yield,
      respectively; alpha-deuterated isotopomers D-18 a and D-18 d gave yields of 33
      and 79% for the same reaction. Double StReCH of 17 was pursued to target
      contiguous stereodiads appropriate for the total synthesis of (-)-epibatidine
      (15). One-pot double StReCH of boronate 17 by two exposures to (S)-D-18 a (<=66 %
      ee), followed by work-up with KOOH, gave the expected stereodiad product in 16%
      yield (d.r.~67:33). The comparable reaction using two exposures to (S)-D-18 d
      (<=90% ee) delivered the expected bisacetal containing stereodiad (R,R)-DD-48 in
      40% yield (>=98% ee, d.r.=85:15). Double StReCH of 17 using (S)-D-18 d (<=90% ee)
      followed by (R)-D-18 d (<=90% ee) likewise gave (R,S)-DD-48 in 49% yield (>=97%
      ee, d.r.=79:21). (R,S)-DD-48 was converted to a dideuterated isotopomer of a
      synthetic intermediate in Corey's synthesis of 15.

PMID- 24127120
TI  - Genetic susceptibility to nosocomial pneumonia, acute respiratory distress
      syndrome and poor outcome in patients at risk of critical illness.
AB  - Genetic susceptibility may partially explain the clinical variability observed
      during the course of similar infections. To establish the contribution of genetic
      host factors in the susceptibility to critical illness, we genotyped 750 subjects
      (419 at high risk of critical illness) for 14 single nucleotide polymorphisms
      (SNPs) in the xenobiotics detoxification/oxidative stress and vascular
      homeostasis metabolic pathways. In the group of nosocomial pneumonia (NP; 268
      patients) the risk of acute respiratory distress syndrome (ARDS) is significantly
      higher for the carriers of CYP1A1 rs2606345 T/T genotypes and AhR rs2066853 G/A
      A/A genotypes. AGTR1 rs5186 allele C is more common among NP non-survivors. The
      duration of stay in intensive care units (ICU) is higher for NP patients with
      ABCB1 rs1045642-T allele. The cumulative effect of the risk alleles in the genes
      comprising two sets of genes partners (xenobiotics detoxification: CYP1A1, AhR
      and RAS family: ACE, AGT, AGTR1) is associated with the development of both NP
      and ARDS. 

PMID- 24127121
TI  - Piperlonguminine downregulates endothelial protein C receptor shedding in vitro
      and in vivo.
AB  - Endothelial cell protein C receptor (EPCR) plays an important role in coagulation
      and inflammation. EPCR can be shed from the cell surface, and this is mediated by
      tumor necrosis factor-alpha-converting enzyme (TACE). Piperlonguminine (PL), an
      important component of Piper longum fruits, is known to exhibit
      antihyperlipidemic, antiplatelet, and antimelanogenesis activities. However,
      little is known about the effects of PL on EPCR shedding. Here, we investigated
      this issue by monitoring the effects of PL on phorbol-12-myristate 13-acetate
      (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and
      underlying mechanisms. PL induced potent inhibition of PMA, and CLP induced EPCR
      shedding through suppression of TACE expression. And treatment with PL resulted
      in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases
      (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, PL might have
      potential as an anti-sEPCR shedding reagent against PMA- and CLP-mediated EPCR
      shedding. 

PMID- 24127122
TI  - Low PIP4K2B expression in human breast tumors correlates with reduced patient
      survival: A role for PIP4K2B in the regulation of E-cadherin expression.
AB  - Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase beta (PIP4K2B) directly
      regulates the levels of two important phosphoinositide second messengers,
      PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has
      been linked to the regulation of gene transcription, to TP53 and AKT activation,
      and to the regulation of cellular reactive oxygen accumulation. However, its role
      in human tumor development and on patient survival is not known. Here, we have
      interrogated the expression of PIP4K2B in a cohort (489) of patients with breast
      tumor using immunohistochemical staining and by a meta-analysis of gene
      expression profiles from 2,999 breast tumors, both with associated clinical
      outcome data. Low PIP4K2B expression was associated with increased tumor size,
      high Nottingham histological grade, Ki67 expression, and distant metastasis,
      whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan
      Meier curves showed that both high and low PIP4K2B expression correlated with
      poorer patient survival compared with intermediate expression. In normal (MCF10A)
      and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression,
      using short hairpin RNA interference-mediated knockdown, led to a decrease in the
      transcription and expression of the tumor suppressor protein E-cadherin (CDH1).
      In MCF10A cells, knockdown of PIP4K2B enhanced TGF-beta-induced epithelial to
      mesenchymal transition (EMT), a process required during the development of
      metastasis. Analysis of gene expression datasets confirmed the association
      between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and
      enhancement of TGF-beta-induced EMT by reduced PIP4K2B expression might, in part,
      explain the association between low PIP4K2B expression and poor patient survival.

PMID- 24127123
TI  - Clinical performance of contrast enhanced abdominal pediatric MRI with fast
      combined parallel imaging compressed sensing reconstruction.
AB  - PURPOSE: To deploy clinically, a combined parallel imaging compressed sensing
      method with coil compression that achieves a rapid image reconstruction, and
      assess its clinical performance in contrast-enhanced abdominal pediatric MRI.
      MATERIALS AND METHODS: With Institutional Review Board approval and informed
      patient consent/assent, 29 consecutive pediatric patients were recruited. Dynamic
      contrast-enhanced MRI was acquired on a 3 Tesla scanner using a dedicated 32
      channel pediatric coil and a three-dimensional SPGR sequence, with pseudo-random
      undersampling at a high acceleration (R = 7.2). Undersampled data were
      reconstructed with three methods: a traditional parallel imaging method and a
      combined parallel imaging compressed sensing method with and without coil
      compression. The three sets of images were evaluated independently and blindly by
      two radiologists at one siting, for overall image quality and delineation of
      anatomical structures. Wilcoxon tests were performed to test the hypothesis that
      there was no significant difference in the evaluations, and interobserver
      agreement was analyzed. RESULTS: Fast reconstruction with coil compression did
      not deteriorate image quality. The mean score of structural delineation of the
      fast reconstruction was 4.1 on a 5-point scale, significantly better (P < 0.05)
      than traditional parallel imaging (mean score 3.1). Fair to substantial
      interobserver agreement was reached in structural delineation assessment.
      CONCLUSION: A fast combined parallel imaging compressed sensing method is
      feasible in a pediatric clinical setting. Preliminary results suggest it may
      improve structural delineation over parallel imaging.

PMID- 24127124
TI  - Development of azo-based fluorescent probes to detect different levels of
      hypoxia.
AB  - Let it shine: New hypoxia-sensitive fluorescent probes were developed; they
      consist of a rhodamine moiety with an azo group directly conjugated to the
      fluorophore. Because of an ultrafast conformational change around the N?N bond,
      the compounds are nonfluorescent under normoxia. However, under hypoxia, the azo
      group is reduced, and a strongly fluorescent rhodamine derivative is released. 

PMID- 24127127
TI  - Usefulness of India ink artifact in steady-state free precession pulse sequences
      for detection and quantification of intramyocardial fat.
AB  - PURPOSE: In steady state free precession (SSFP) images acquired with a repetition
      time/echo time (TR/TE) ~ 2, fat is surrounded by a black boundary, called "India
      Ink" artifact. Indian Ink artifact may improve detection of intramyocardial fat.
      Aims of this study were: (i) to assess the accuracy of SSFP technique for the
      detection of fat metaplasia in remote myocardial infarction (RMI); (ii) to
      evaluate the inter- and intraobserver reproducibility for the quantification of
      intramyocardial fat using SSFP and fast spin echo/short TI inversion recovery
      (FSE/STIR) techniques. MATERIALS AND METHODS: A total of 200 patients (age 64 +/-
      10 years) with RMI (>1000 days) underwent MRI using a 1.5 Tesla (T) scanner. SSFP
      images (with a TR/TE ~2), FSE and STIR images were acquired in short and long
      axis views. Fat was detected in FSE/STIR and SSFP images and its extent manually
      measured . The inter- and intraobserver agreement for the quantification of fat
      metaplasia using both the SSFP image and the FSE images was evaluated. RESULTS:
      Left ventricle intramyocardial fat was detected in SSFP images of 95 patients
      (47.5%) and in FSE/STIR images of 84 patients (42%). A very good agreement was
      found using the SSFP technique between investigators. CONCLUSION: SSFP sequence
      with TR/TE=2 is a valuable technique for identifying and quantifying the presence
      of fat tissue within the left ventricle myocardium in RMI.

PMID- 24127125
TI  - Periprosthetic osteolysis after total hip replacement: molecular pathology and
      clinical management.
AB  - Periprosthetic osteolysis is a serious complication of total hip replacement
      (THR) in the medium to long term. Although often asymptomatic, osteolysis can
      lead to prosthesis loosening and periprosthetic fracture. These complications
      cause significant morbidity and require complex revision surgery. Here, we review
      advances in our understanding of the cell and tissue response to particles
      produced by wear of the articular and non-articular surfaces of prostheses. We
      discuss the molecular and cellular regulators of osteoclast formation and bone
      resorptive activity, a better understanding of which may lead to pharmacological
      treatments for periprosthetic osteolysis. We describe the development of imaging
      techniques for the detection and measurement of osteolysis around THR prostheses,
      which enable improved clinical management of patients, provide a means of
      evaluating outcomes of non-surgical treatments for periprosthetic osteolysis, and
      assist in pre-operative planning for revision surgery. Finally, there have been
      advances in the materials used for bearing surfaces to minimise wear, and we
      review the literature regarding the performance of these new materials to date. 

PMID- 24127126
TI  - Cat's whiskers flavonoid attenuated oxidative DNA damage and acute inflammation:
      its importance in lymphocytes of patients with rheumatoid arthritis.
AB  - Cleome gynandra L. (Capparidaceae) is one of the vegetables commonly known as
      'Hurhur' and 'Karaila' in India, 'Pe Hua Tsai' in China and "Cat's whiskers" in
      English. Present study was aimed to characterize previously isolated Cat's
      whiskers flavonoid as 5-hydroxy-3, 7, 4' -trimethoxyflavone (5HTMF) and to
      evaluate its effect on carrageenan-induced acute inflammation in rats and
      hydrogen peroxide induced DNA damage in mouse macrophages. The ex vivo effect of
      5HTMF upon generation of free radicals in the mononuclear lymphocytes of patients
      with rheumatoid arthritis (RA) was also evaluated. 5HTMF not only reduce the
      swelling of hind paw in rats from 1 to 3 h of carrageenan injection but also
      decreased serum nitric oxide (NO) production. Toxic hydrogen peroxide induced
      oxidative DNA damage that was significantly decreased by 5HTMF. Though oxidative
      stress is a potential biomarker for determining disease activity in patients with
      RA, surprisingly 5HTMF inhibited the superoxide, hydroxyl and NO radicals in the
      isolated peripheral blood mononuclear lymphocytes of patients with RA. From the
      above study, it may be concluded 5HTMF attenuated acute inflammation by
      inhibiting NO and by protecting the oxidative DNA damage due to hydrogen peroxide
      scavenging property. It was also equally effective in scavenging the free
      radicals in lymphocytes of patients with RA. Collectively, our results indicate
      that 5HTMF as well as leafy vegetable of Cat's whiskers may be a promising
      nontoxic food alternative in attenuating the oxidative stress, meriting further
      studies on other human inflammatory cells. 

PMID- 24127128
TI  - Expression and purification of a human anti-cyclin D1 single-chain variable
      fragment antibody AD5 and its characterization.
AB  - Cyclin D1 plays an important role in cell cycle progression. Increasing evidence
      indicates that cyclin D1 is overexpressed in the majority of tumor cells and has
      become a potential target for tumor therapy. However, little research has been
      done on the specific inhibition of cyclin D1 for cancer therapy. With the rapid
      development of the phage display antibody library technique, single-chain
      variable fragment (scFv) antibodies have emerged, which have tremendous
      application prospects in cancer therapy and diagonosis. In this study, a human
      scFv binding specifically to cyclin D1 (AD5) that was derived from a human semi
      synthetic scFv phage library was expressed in the soluble form in Escherichia
      coli (E. coli) HB2151 cells. To characterize AD5, soluble AD5 was purified
      successfully through ammonium sulfate precipitation and affinity chromatography
      from the culture supernatant of AD5/HB2151. ELISA assay revealed that purified
      soluble AD5 could specifically bind to human recombinant cyclin D1 with
      approximately (1.19+/-0.056) x 107 M-1 affinity constant and showed approximately
      52% competitive inhibition with the anti-cyclin D1 polyclonal antibody for
      binding to cyclin D1 in vitro. These results suggest that the scFv antibody
      against cyclin D1 may be a novel potential tool for targeting cyclin D1 in cancer
      therapy and diagnosis. 

PMID- 24127130
TI  - Spatiotemporal analysis of land use and land cover change in the Brazilian
      Amazon.
AB  - This paper provides a comparative analysis of land use and land cover (LULC)
      changes among three study areas with different biophysical environments in the
      Brazilian Amazon at multiple scales, from per-pixel, polygon, census sector, to
      study area. Landsat images acquired in the years of 1990/1991, 1999/2000, and
      2008/2010 were used to examine LULC change trajectories with the post
      classification comparison approach. A classification system composed of six
      classes - forest, savanna, other-vegetation (secondary succession and
      plantations), agro-pasture, impervious surface, and water, was designed for this
      study. A hierarchical-based classification method was used to classify Landsat
      images into thematic maps. This research shows different spatiotemporal change
      patterns, composition and rates among the three study areas and indicates the
      importance of analyzing LULC change at multiple scales. The LULC change analysis
      over time for entire study areas provides an overall picture of change trends,
      but detailed change trajectories and their spatial distributions can be better
      examined at a per-pixel scale. The LULC change at the polygon scale provides the
      information of the changes in patch sizes over time, while the LULC change at
      census sector scale gives new insights on how human-induced activities (e.g.,
      urban expansion, roads, and land use history) affect LULC change patterns and
      rates. This research indicates the necessity to implement change detection at
      multiple scales for better understanding the mechanisms of LULC change patterns
      and rates.

PMID- 24127129
TI  - Laboratory tests for paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder that
      is often suspected in a patient presenting with non-immune hemolytic anemia
      associated with pancytopenia or venous thrombosis. This disorder is a consequence
      of acquired somatic mutations in the phosphatidylinositol glycan class A (PIG-A)
      gene in the hematopoietic stem cells (HSC) of patients. The presence of these
      mutations leads to production of blood cells with decreased glycosyl
      phosphatidylinositol-anchored cell surface proteins, making red blood cells
      derived from the clone more sensitive to complement mediated hemolysis. The
      diagnosis of PNH may be difficult in some cases due a low proportion of PNH cells
      in the blood and occasionally due to difficulties in selecting the most
      appropriate diagnostic studies. The latest generation of tests allow for
      detection of very small populations of PNH cells, for following the natural
      course and response to therapy of the disease, and for helping to decide when to
      initiate therapy with monoclonal antibody targeting the terminal complement
      protein C5 (Eculizumab), anticoagulation, and in some cases allogeneic HSC
      transplant. In this article, we review the different diagnostic tests available
      to clinicians for PNH diagnosis.

PMID- 24127132
TI  - Strategies for improved 3D small-tip fast recovery imaging.
AB  - PURPOSE: Small-tip fast recovery (STFR) imaging is a recently proposed steady
      state sequence that has similar image contrast as balanced steady-state free
      precession but has the potential to simultaneously remove banding artifacts and
      transient fluctuation. STFR relies on a "tip-up" radiofrequency (RF) pulse
      tailored to the accumulated phase during the free precession (data acquisition)
      interval, designed to bring spins back to the longitudinal axis, thereby
      preserving transverse magnetization as longitudinal magnetization for the next
      pulse repetition time. We recently proposed an RF-spoiled STFR sequence suitable
      for thin slab imaging, however, in many applications, e.g., functional magnetic
      resonance imaging or isotropic-resolution structural imaging, three-dimensional
      (3D) steady-state imaging is desirable. Unfortunately, 3D STFR imaging is
      challenging due to the need for 3D tailored RF pulses. Here, we propose new
      strategies for improved 3D STFR imaging, based on (i) unspoiled imaging, and (ii)
      joint design of nonslice-selective tip-down/tip-up RF pulses. THEORY AND METHODS:
      We derive an analytic signal model for the proposed unspoiled STFR sequence, and
      propose two strategies for designing the 3D tailored tip-down/tip-up RF pulses.
      We validate the analytic results using phantom and in vivo imaging experiments.
      RESULTS: Our analytic model and imaging experiments demonstrate that the proposed
      unspoiled STFR sequence is less sensitive to tip-up excitation error compared to
      the corresponding spoiled sequence, and may, therefore, be an attractive
      candidate for 3D imaging. The proposed "joint" RF pulse design method, in which
      we formulate the tip-down/tip-up RF pulse design task as a magnitude least
      squares problem, produces modest improvement over a simpler "Separate" design
      approach. Using the proposed unspoiled sequence and joint RF pulse design, we
      demonstrate proof-of-principle 3D STFR brain images with balanced steady-state
      free precession-like signal properties but with reduced banding. CONCLUSION:
      Using the proposed unspoiled sequence and joint RF pulse design, STFR brain
      images in a 3D region of interest with balanced steady-state free precession-like
      signal properties but with reduced banding can be obtained.

PMID- 24127134
TI  - Differences in tip visibility and nerve block parameters between two echogenic
      needles during a simulation study with inexperienced anesthesia trainees.
AB  - Needle tip visualization during ultrasound-guided regional anesthesia (UGRA) is
      necessary for safety and efficacy. However, disruption of the image of the needle
      tip driven toward the target is a general problem, especially for beginners. The
      purpose of this study was to compare performance parameters between using the
      Sonoplex and Stimuplex D-Plus echogenic needles in a simulated ultrasound-guided
      interventional task by inexperienced anaesthesia residents. After a standardized
      training session, 28 anesthesiology residents performed simulated nerve blocks in
      a beef phantom with each needle. All ultrasound images were digitally stored for
      analysis. The absolute time the needle tip was in view, total procedure time, and
      angle of needle insertion were subsequently measured objectively by two single
      investigators. The procedures that used the Sonoplex echogenic needle had
      significantly better tip visibility and shorter total procedure time at insertion
      angles between 42 degrees  and 64 degrees  relative to the phantom surface. We
      have demonstrated that inexperienced users who used the Sonoplex echogenic needle
      were able to complete the procedure more quickly. Needles with improved
      visibility would be a very useful addition to UGRA for inexperienced users. 

PMID- 24127135
TI  - A new efficient method for synaptic vesicle quantification reveals differences
      between medial prefrontal cortex perforated and nonperforated synapses.
AB  - Communication between neurons is mediated by the release of neurotransmitter
      containing vesicles from presynaptic terminals. Quantitative characterization of
      synaptic vesicles can be highly valuable for understanding mechanisms underlying
      synaptic function and plasticity. We performed a quantitative ultrastructural
      analysis of cortical excitatory synapses by mean of a new, efficient method, as
      an alternative to three-dimensional (3D) reconstruction. Based on a hierarchical
      sampling strategy and unequivocal identification of the region of interest,
      serial sections from excitatory synapses of medial prefrontal cortex (mPFC) of
      six Sprague-Dawley rats were acquired with a transmission electron microscope.
      Unbiased estimates of total 3D volume of synaptic terminals were obtained through
      the Cavalieri estimator, and adequate correction factors for vesicle profile
      number estimation were applied for final vesicle quantification. Our analysis was
      based on 79 excitatory synapses, nonperforated (NPSs) and perforated (PSs)
      subtypes. We found that total number of docked and reserve-pool vesicles in PSs
      significantly exceeded that in NPSs (by, respectively, 77% and 78%). These
      differences were found to be related to changes in size between the two subtypes
      (active zone area by 86%; bouton volume by 105%) rather than to postsynaptic
      density shape. Positive significant correlations were found between number of
      docked and reserve-pool vesicles, active zone area and docked vesicles, and
      bouton volume and reserve pool vesicles. Our method confirmed the large size of
      mPFC PSs and a linear correlation between presynaptic features of typical
      hippocampal synapses. Moreover, a greater number of docked vesicles in PSs may
      promote a high synaptic strength of these synapses.

PMID- 24127133
TI  - B Lymphocytes in obesity-related adipose tissue inflammation and insulin
      resistance.
AB  - Obesity-related insulin resistance is a chronic inflammatory condition that often
      gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro
      inflammatory T cells and macrophages in promoting local inflammation in tissues
      such as visceral adipose tissue (VAT) leading to insulin resistance. More
      recently, B cells have emerged as an additional critical player in orchestrating
      these processes. B cells infiltrate VAT and display functional and phenotypic
      changes in response to diet-induced obesity. B cells contribute to insulin
      resistance by presenting antigens to T cells, secreting inflammatory cytokines,
      and producing pathogenic antibodies. B cell manipulation represents a novel
      approach to the treatment of obesity-related insulin resistance and potentially
      to the prevention of T2D. This review summarizes the roles of B cells in
      governing VAT inflammation and the mechanisms by which these cells contribute to
      altered glucose homeostasis in insulin resistance. 

PMID- 24127136
TI  - Efficacy of initial Basal-supported oral therapy with sitagliptin in untreated
      type 2 diabetes.
AB  - INTRODUCTION: The present study assessed the efficacy of initial basal-supported
      oral therapy (BOT) with sitagliptin for achievement of glycemic control and
      subsequent switching from BOT to sitagliptin-based oral therapy. METHODS:
      Nineteen recently diagnosed type 2 diabetic patients who had received no
      antidiabetic medication in the previous 2 years were sequentially examined for
      the 24-week study. Patients were initially treated with a combination of insulin
      glargine and sitagliptin. Sitagliptin was initiated and maintained at a dose of
      50 mg/day, and insulin glargine was started at a dose of 4 U at bedtime and
      adjusted if needed. RESULTS: During the 24-week treatment period, 12 patients
      (63%) achieved HbA1c levels <7% (mean BOT duration 13.7 +/- 5.6 weeks) and
      switched from BOT to sitagliptin monotherapy or in combination with metformin
      (achievers). The remaining seven patients (37%) failed to achieve HbA1c levels
      <7% (non-achievers) and continued on BOT. Both FPG and HbA1c in achievers
      significantly dropped at 4, 8, 12 and 24 weeks from baseline, while those in non
      achievers significantly decreased at 12 and 24 weeks from baseline, but failed to
      reach target glycemic control. There were statistically significant differences
      in FPG at 4, 8, 12 and 24 weeks and in HbA1c at 8, 12 and 24 weeks between
      achievers and non-achievers. Body weight and BMI in achievers were significantly
      reduced at 12 and 24 weeks, but those in non-achievers did not change
      significantly. Dosage of concomitant insulin during BOT was significantly lower
      in achievers compared to non-achievers. Non-achievers had a similar CPI, a
      measure of insulin secretion capacity, to achievers, but significantly showed an
      insulin resistance index (value of 20/[fasting CPR * FPG]), in comparison to
      achievers. CONCLUSION: Initiating BOT with sitagliptin followed by sitagliptin
      based oral therapy is a useful option in untreated and poorly controlled patients
      with type 2 diabetes.

PMID- 24127137
TI  - Bridging the gap between genetic associations and molecular mechanisms for type 2
      diabetes.
AB  - Type 2 diabetes is a global pandemic for which there is currently no disease
      modifying treatment. New and targeted therapeutics are greatly needed, but
      progress in identifying novel targets for therapeutic intervention is severely
      hampered by poor understanding of disease pathogenesis. Over the past 6 years,
      the success of genome-wide association studies has led to an unprecedented
      increase in the number of loci robustly associating with type 2 diabetes risk.
      Each of these signals offers the opportunity to uncover biological insights into
      disease pathogenesis, which, if harnessed effectively, hold the promise to
      deliver new pathways for therapeutic intervention, strategies for patient
      stratification, and potentially, biomarkers for identifying those at greatest
      risk of developing diabetes. We review the progress that has been made and the
      approaches being adopted and discuss the inherent challenges in moving from
      association signals, which largely map to poorly annotated sequence, to
      transcripts, mechanisms, and disease biology. 

PMID- 24127139
TI  - A convenient and selective palladium-catalyzed aerobic oxidation of alcohols.
AB  - An efficient procedure for the oxidation of primary and secondary alcohols to
      aldehydes and ketones, respectively, with molecular oxygen under ambient
      conditions has been achieved. By applying catalytic amounts of Pd(OAc)2 in the
      presence of tertiary phosphine oxides (O=PR3) as ligands, a variety of substrates
      are selectively oxidized without formation of ester byproducts. Spectroscopic
      investigations and DFT calculations suggest stabilization of the active
      palladium(II) catalyst by phosphine oxide ligands.

PMID- 24127138
TI  - Design and application of specific 16S rDNA-targeted primers for assessing
      endophytic diversity in Dendrobium officinale using nested PCR-DGGE.
AB  - Novel specific 16S rDNA-targeted primers were successfully designed and applied
      to the characterization of endophytic diversity in Dendrobium officinale. Using
      the popular universal bacterial primers 27f/1492r, the fragments of chloroplast
      and mitochondrion 16S/18S rDNA were amplified from D. officinale. They shared
      high nucleotide identity with the chloroplast 16S rDNAs (99-100 %) and with the
      mitochondrion 18S rDNAs (93-100 %) from various plants, respectively, and both
      shared 73-86 % identities with the bacterial 16S rDNA sequences in GenBank. The
      current bacterial universal primers, including 27f/1492r, match well with the
      chloroplast and mitochondrion 16S/18S rDNAs, which accordingly renders these
      primers not useful for endophytic diversity analysis. Novel 16S rDNA-targeted
      primers fM1 (5'-CCGCGTGNRBGAHGAAGGYYYT-3') and rC5 (5'-TAATCCTGTTTGCTCC CCAC-3')
      were designed, which show good specificity compared to the 16S/18S rDNAs of D.
      officinale, and perfect universality within bacteria except for Cyanobacteria.
      The primers fM1/rC5, together with 515f-GC/rC5, which overlaps the whole V4
      region of 16S rDNA, were subjected to nested polymerase chain reaction denaturing
      gradient gel electrophoresis (PCR-DGGE) to analyze the diversity of endophytic
      bacteria in D. officinale from three different sources in China. The results
      showed diversities in roots and stems of the plants from all three locations.
      Altogether, 29 bands were identified as bacteria, with the dominant group being
      Proteobacteria and the dominant genus being Burkholderia, some of which commonly
      has the function of nitrogen fixation and thus may play potentially important
      roles in D. officinale. Therefore, the nested PCR-DGGE method based on the novel
      primers provides a good alternative for investigating the communities and roles
      of endophytes in D. officinale. 

PMID- 24127140
TI  - Abuse of the Epworth Sleepiness Scale.

PMID- 24127141
TI  - Impact of treatment with continuous positive airway pressure (CPAP) on weight in
      obstructive sleep apnea.
AB  - STUDY OBJECTIVE: To determine the impact of continuous positive airway pressure
      (CPAP) on weight change in persons with obstructive sleep apnea (OSA). DESIGN
      SETTING AND PARTICIPANTS: The Apnea Positive Pressure Long-term Efficacy Study
      (APPLES) was a 6-month, randomized, double-blinded sham-controlled multicenter
      clinical trial conducted at 5 sites in the United States. Of 1,105 participants
      with an apnea hypopnea index >= 10 events/ hour initially randomized, 812 had
      body weight measured at baseline and after 6 months of study. INTERVENTION: CPAP
      or Sham CPAP. MEASUREMENTS: Body weight, height, hours of CPAP or Sham CPAP use,
      Epworth Sleepiness Scale score. RESULTS: Participants randomized to CPAP gained
      0.35 +/- 5.01 kg, whereas those on Sham CPAP lost 0.70 +/- 4.03 kg (mean +/- SD,
      p = 0.001). Amount of weight gain with CPAP was related to hours of device
      adherence, with each hour per night of use predicting a 0.42 kg increase in
      weight. This association was not noted in the Sham CPAP group. CPAP participants
      who used their device >= 4 h per night on >= 70% of nights gained the most weight
      over 6 months in comparison to non-adherent CPAP participants (1.0 +/- 5.3 vs. 
      0.3 +/- 5.0 kg, p = 0.014). CONCLUSIONS: OSA patients using CPAP may gain a
      modest amount of weight with the greatest weight gain found in those most
      compliant with CPAP. COMMENTARY: A commentary on this article appears in this
      issue on page 995. CITATION: Quan SF; Budhiraja R; Clarke DP; Goodwin JL;
      Gottlieb DJ; Nichols DA; Simon RD; Smith TW; Walsh JK; Kushida CA. Impact of
      treatment with continuous positive airway pressure (CPAP) on weight in
      obstructive sleep apnea.

PMID- 24127142
TI  - Weigh the options before starting CPAP.

PMID- 24127143
TI  - Mortality of patients with obstructive sleep apnea in Korea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with diverse health
      risks, including death. However, the role of OSA as a risk factor for death has
      never been studied in Asians. This study is aimed at evaluating the influence of
      OSA on the mortality in Korean sleep clinic population. METHODS: A total of 2,240
      patients who underwent in-laboratory full-night polysomnography due to snoring or
      sleep apnea were included. The patients were categorized based on apnea-hypopnea
      index (AHI)/hour. Death records were provided from the Statistics Korea. A Cox
      proportional hazard regression model and Kaplan-Meier survival curve were used
      for analysis and demonstration of the all-cause mortality and cardiovascular
      mortality. RESULTS: The all-cause mortality risk adjusted for age, sex, body mass
      index, diabetes, hypertension, cardiovascular diseases, and previous history of
      stroke was significantly associated with the increased severity of OSA. The
      adjusted hazard ratio (HR) for all-cause mortality in the severe OSA group (AHI
      >= 30) vs. reference group (5 < AHI) was 2.47 (95% confidence interval [CI], 1.09
      5.57) and the adjusted HR for cardiovascular mortality was 4.66 (CI 1.03-21.08).
      After adjusting for whether the patients were treated or untreated, the HR for
      all-cause and cardiovascular mortality in the severe OSA group vs. reference
      group were 2.14 (p = 0.079) and 4.19 (p = 0.076), respectively. CONCLUSIONS: The
      present study showed that the increased mortality was also associated with the
      increased severity of OSA in Koreans as shown in the studies performed in the
      Western countries.

PMID- 24127144
TI  - Serum inflammatory markers in obstructive sleep apnea: a meta-analysis.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been linked to and is
      associated with increased cardiovascular and cerebrovascular morbidity. Ongoing
      inflammatory responses play an important role in this association. Multiple small
      size studies addressing the profile of the inflammatory markers in OSA are
      available therefore we performed a meta-analysis. METHODS: Systematic review of
      medical literature was conducted using PubMed, Cochrane, and EMBASE databases
      from 1968 to 2011 by utilizing the key words obstructive sleep apnea, C-Reactive
      protein, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6),
      interleukin 8 (IL-8), intercellular adhesion molecule (ICAM), vascular cell
      adhesion molecule (VCAM) and Selectins. Inclusion criteria were: full text
      English articles; studies with adult population; reported values for at least one
      of the markers of interest; with at least two separate groups (subjects with OSA
      and control group); OSA was defined as AHI of >= 5/h. RESULTS: Five hundred and
      twelve studies were reviewed for inclusion with 51 studies pooled for analysis
      (30 studies for CRP, 19 studies for TNF-alpha, 8 studies for ICAM, 18 studies for
      IL-6, six studies for VCAM and 5 studies for Selectins). The levels of
      inflammatory markers were higher in patients with OSA compared to control group.
      Standardized pooled Mean differences were calculated to be 1.77 for CRP, 1.03 for
      TNF-alpha, 2.16 for IL-6, 4.22 for IL-8, 2.93 for ICAM, 1.45 for Selectins and
      2.08 for VCAM. CONCLUSIONS: In this meta-analysis, the levels of systemic
      inflammatory markers were found to be higher in OSA patients compared to control
      subjects.

PMID- 24127145
TI  - Excessive daytime sleepiness increases the risk of motor vehicle crash in
      obstructive sleep apnea.
AB  - STUDY OBJECTIVES: (1) To describe the incidence rate of motor vehicle crashes
      (MVCs) in patients with obstructive sleep apnea (OSA); and (2) to investigate MVC
      risk factors in OSA patients. METHODS: A retrospective case-series observational
      study was conducted using data from the West Australian Sleep Health Study at a
      tertiary hospital-based sleep clinic. Participants were patients (N = 2,673)
      referred for assessment of suspected sleep disordered breathing. Questionnaire
      data were collected including age, sex, years of driving, near-misses and MVCs,
      sleepiness, and consumption of alcohol and caffeinated drinks. Overnight
      laboratory-based polysomnography was performed using standard methodology.(1)
      Poisson univariate and negative binomial multivariable regression models were
      used to investigate associations between risk factors and MVC and near-miss risk
      in patients with untreated OSA. RESULTS: In patients with untreated OSA, the
      crash rate was 0.06 MVC/person-year compared with the general community crash
      rate of 0.02 MVC/person-year. The rate ratio comparing very sleepy men with
      normal men was 4.68 (95% CI 3.07, 7.14) for near-misses and 1.27 (95% CI 1.00,
      1.61) for crashes, after adjusting for confounders. In women there was a
      significant association with sleepiness score (p = 0.02) but no dose effect
      across quartiles. CONCLUSIONS: Untreated OSA is associated with an increased risk
      of near-misses in men and women and an increased risk of MVCs in very sleepy men.
      There is a strong association between excessive daytime sleepiness and increased
      report of near-misses. Our data support the observation that it is those patients
      with increased sleepiness regardless of OSA severity who are most at risk.

PMID- 24127146
TI  - Medicare long-term CPAP coverage policy: a cost-utility analysis.
AB  - STUDY OBJECTIVES: CPAP is an effective treatment for OSA that may reduce health
      care utilization and costs. Medicare currently reimburses the costs of long-term
      CPAP therapy only if the patient is adherent during a 90-day trial. If not,
      Medicare requires a repeat polysomnogram (PSG) and another trial which seems
      empirically not cost-effective. We modeled the cost-effectiveness of current
      Medicare policy compared to an alternative policy (clinic-only) without the
      adherence criterion and repeat PSG. DESIGN: Cost-utility and cost-effectiveness
      analysis. SETTING: U.S. Medicare Population. PATIENTS OR PARTICIPANTS: N/A.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We created a decision tree modeling
      (1) clinic only follow-up vs. (2) current Medicare policy. Costs were assigned
      based on Medicare reimbursement rates in 2012. Sensitivity analyses were
      conducted to test our assumptions. We estimated cumulative costs, overall
      adherence, and QALY gained for a 5-year time horizon from the perspective of
      Medicare as the payer. Current Medicare policy is more costly than the clinic
      only policy but has higher net adherence and improved utility. Current Medicare
      policy compared to clinic-only policy costs $30,544 more per QALY. CONCLUSIONS:
      Current CMS policy promotes early identification of those more likely to adhere
      to CPAP therapy by requiring strict adherence standards. The policy effect is to
      deny coverage to those unlikely to use CPAP long-term and prevent wasted
      resources. Future studies are needed to measure long-term adherence in an elderly
      population with and without current adherence requirements to verify the cost
      effectiveness of a policy change.

PMID- 24127147
TI  - EEG power during waking and NREM sleep in primary insomnia.
AB  - OBJECTIVE: Pathophysiological models of insomnia invoke the concept of 24-hour
      hyperarousal, which could lead to symptoms and physiological findings during
      waking and sleep. We hypothesized that this arousal could be seen in the waking
      electroencephalogram (EEG) of individuals with primary insomnia (PI), and that
      waking EEG power would correlate with non-REM (NREM) EEG. METHODS: Subjects
      included 50 PI and 32 good sleeper controls (GSC). Five minutes of eyes closed
      waking EEG were collected at subjects' usual bedtimes, followed by
      polysomnography (PSG) at habitual sleep times. An automated algorithm and visual
      editing were used to remove artifacts from waking and sleep EEGs, followed by
      power spectral analysis to estimate power from 0.5-32 Hz. RESULTS: We did not
      find significant differences in waking or NREM EEG spectral power of PI and GSC.
      Significant correlations between waking and NREM sleep power were observed across
      all frequency bands in the PI group and in most frequency bands in the GSC group.
      CONCLUSIONS: The absence of significant differences between groups in waking or
      NREM EEG power suggests that our sample was not characterized by a high degree of
      cortical arousal. The consistent correlations between waking and NREM EEG power
      suggest that, in samples with elevated NREM EEG beta activity, waking EEG power
      may show a similar pattern.

PMID- 24127148
TI  - Loss of rapid eye movement sleep atonia in patients with REM sleep behavioral
      disorder, narcolepsy, and isolated loss of REM atonia.
AB  - STUDY OBJECTIVES: To compare the amounts of REM sleep without atonia (RSWA)
      between patients with REM sleep behavior disorder (RBD), "isolated loss of REM
      atonia," narcolepsy, and control subjects and determine if there were threshold
      values for the amount of RSWA that differentiate each group from controls.
      METHODS: Retrospective analyses of polysomnography (PSG) records were used
      employing strict quantitative criteria for the measurement of phasic and tonic
      EMG activity during REM sleep. The PSG recordings of 47 individuals were analyzed
      (RBD 16, isolated loss of REM atonia 11, narcolepsy 10, control 10). RESULTS:
      Patients with the diagnosis of isolated loss of REM atonia had significantly
      lower levels of EMG activity during REM sleep than those with RBD but higher than
      control subjects. RSWA was higher in narcolepsy than in loss of REM atonia but
      lower than for RBD patients. Receiver operating characteristic (ROC) curves
      provided threshold values with high specificity and sensitivity in all patient
      groups with a cutoff value >= 1.22% (100% correctly classified) for phasic and >=
      3.17% for tonic (92% correctly classified) EMG activity in RBD. CONCLUSION:
      Quantification of REM sleep EMG activity can successfully differentiate RBD and
      isolated loss of REM atonia patients from controls. The consistently increased
      amount of RSWA in patients with narcolepsy indicates that this can be an
      additional marker for a diagnosis of narcolepsy. Longitudinal studies of patients
      with isolated loss of REM atonia are needed to evaluate if these patients are at
      risk of developing RBD or neurodegenerative disorders.

PMID- 24127149
TI  - Short duration of sleep is associated with hyperleptinemia in Taiwanese adults.
AB  - BACKGROUND: Higher plasma levels of leptin have been associated with increased
      cardiometabolic risk. The aim of this study was to investigate the association
      between short duration of sleep and hyperleptinemia in Taiwanese adults. METHODS:
      We examined the association between duration of sleep and hyperleptinemia in 254
      men and women recruited from the physical examination center at a regional
      hospital in southern Taiwan. Hyperleptinemia was defined as a plasma leptin level
      of 8.13 ng/mL and above. Short sleep duration was defined as < 6.5 h/day.
      Multiple logistic regression analysis was used to assess the association between
      short duration of sleep and hyperleptinemia. RESULTS: In females, short duration
      of sleep (< 6.5 h/day; OR = 2.15, 95% CI = 0.99-4.78), greater hip circumference
      (OR = 3.00, CI = 1.13-8.78), higher percent body fat (OR = 1.75, CI = 1.07-2.95),
      and higher white blood cell counts (OR = 1.67, CI = 1.26-2.28) were associated
      with an increased risk of hyperleptinemia. In males, greater body weight was
      significantly associated with an increased risk of hyperleptinemia (OR = 3.55,
      95% CI = 1.46-10.23). There was also a trend of association (p = 0.096) between
      short duration of sleep and an increased risk of hyperleptinemia (OR = 4.98, 95%
      CI = 0.80-42.40). CONCLUSIONS: In this study of healthy Taiwanese adults, short
      duration of sleep was significantly associated with hyperleptinemia in women, and
      the association was independent of adiposity.

PMID- 24127150
TI  - The association between sleep duration and self-rated health in the Korean
      general population.
AB  - STUDY OBJECTIVES: Sleep duration is recognized as one of the most common issues
      in modern society. Self-rated health is a commonly used subjective health measure
      based on a single question asking individuals to rate their general health on a
      four- or five-point scale. However, few studies have examined the relationship
      between sleep duration and self-rated health. Here, we examined the association
      between sleep duration and poor self-rated health, using a large representative
      sample of the general Korean adult population. DESIGN: We conducted a cross
      sectional study of 15,252 participants in the Korea National Health and Nutrition
      Examination Survey IV (2007-2009) who were aged 19 years and older. Sleep
      duration was categorized as <= 5, 6, 7, 8, or >= 9 hours. The main outcome of
      interest was poor self-rated health (n = 3,705, 19.7%). Multiple logistic
      regression analysis was performed to examine the association between sleep
      duration and self-rated health. RESULTS: We found both short (<= 5 h) and long
      (>= 9 h) sleep duration to be associated with poor self-rated health independent
      of sociodemographic, health risk, and health status variables. Compared with 7-h
      sleep duration, the multivariate odds of poor self-rated health were 1.358 times
      higher (95% CI 1.167-1.580) with short sleep duration and 1.322 times higher (95%
      CI 1.091-1.601) with long sleep duration. This association persisted in subgroup
      analyses of gender, body mass index, and age by gender. CONCLUSIONS: In a large
      representative sample of the Korean general adult population, compared with sleep
      duration of 7 hours, we found a positive association between short and long sleep
      duration and poor self-rated health in Korean adults. Furthermore, the
      association between sleep duration and poor self-rated health was consistently
      present in subgroups divided by gender, age, and BMI.

PMID- 24127152
TI  - Presenting symptoms in pediatric restless legs syndrome patients.
AB  - OBJECTIVE: The diagnosis restless legs syndrome (RLS) in children depends on the
      history told by the child and his parents. The description of symptoms given by
      the child himor herself is most important. Additional criteria are, among others,
      the results of polysomnography (PSG). Description of the presenting symptoms is
      the aim of the study. METHODS: Survey in two European pediatric sleep centers of
      presenting symptoms in children who after a detailed work-up proved to have RLS.
      RESULTS: Fifty-two percent of the 31 children presented with symptoms similar to
      those mentioned in the "four questions" relevant for the diagnosis of RLS. In the
      other patients the description included often very colourful wordings, such as
      "ants or spiders in the legs, legs want to kick, need to stretch." All children
      were tired or sleepy during daytime and nearly all reported an urge to move.
      Insomnia was mentioned by 61% of the patients. The presenting symptoms did not
      differ significantly from those mentioned in a previous study in the US, but did
      so when compared to adults with RLS. PSG revealed an abnormal periodic limb
      movement index in 81% of the children. CONCLUSIONS: The description of presenting
      symptoms in children with the final diagnosis of RLS differs from that in adults.
      The results of this European study corroborate those from the US.

PMID- 24127151
TI  - Restless legs syndrome in an appalachian primary care population: prevalence,
      demographic and lifestyle correlates, and burden.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common and distressing sensorimotor
      disorder of unknown etiology. While the epidemiology of RLS has been examined in
      several North American and European studies, research on RLS and RLS burden in
      poor, rural populations, including those residing in Appalachia, remains sparse.
      In this study, we investigated RLS prevalence in an Appalachian primary care
      population and examined the association of RLS to demographic factors, lifestyle
      characteristics, sleep quality, and mood disorders. METHODS: Participants of this
      anonymous survey study were community-dwelling adults aged >= 18 years visiting
      one of 4 West Virginia primary care clinics. Data gathered included detailed
      information on sleep patterns, demographic characteristics, lifestyle factors,
      and health/medical history; the survey also included questions specific to RLS
      diagnosis and severity. Response rates were excellent, with 68% of eligible
      adults contacted returning completed surveys (N = 1,424/2,087). Pregnant women (N
      = 65) and those with missing data on key variables (N = 142) were excluded from
      the analyses. RESULTS: Of the 1,217 participants included in the final analytic
      sample, 19.6% (18.2% with symptoms at least once/month) met the 4 IRLSSG
      diagnostic criteria in the absence of positional discomfort or leg cramps; 14.5%
      reported RLS symptoms at least once/week and 10.1% indicated symptoms >= 3*/week.
      Excluding respondents with diabetes, kidney disease, or anemia reduced these
      rates only slightly. Those with RLS were more likely to be older, female, lower
      income, unemployed, disabled, non-Hispanic white, and less likely to be college
      educated than those without RLS. Mood and sleep impairment were significantly
      elevated in those with RLS; after adjustment for demographic and lifestyle
      characteristics, health history, and other factors, those with RLS remained
      significantly more likely to indicate a history of depression (adjusted odds
      ratio [OR] = 1.9; 95% confidence interval [CI] = 1.4, 2.6) and anxiety (OR = 1.6,
      CI 1.1, 2.2), to report sleep impairment both 4 (OR = 2.4, CI 1.6, 3.7) and 7
      days/week (OR = 1.8, CI 1.3, 2.4), and a mean sleep duration < 5 h/night (OR =
      1.7, CI 1.2, 2.3). These associations increased in both strength and magnitude
      with increasing symptom frequency (p's for trend <= 0.01). CONCLUSIONS: Findings
      of this preliminary anonymous survey study suggest that RLS prevalence is high in
      this Appalachian primary care population and that RLS is associated with
      significant burden in terms of both mood and sleep impairment.

PMID- 24127153
TI  - Sleep technologists educational needs assessment: a survey of polysomnography,
      electroneurodiagnostic technology, and respiratory therapy education program
      directors.
AB  - STUDY OBJECTIVES: In this study, we assessed the community and educational needs
      for sleep technologists by surveying program directors of nationally accredited
      polysomnography, electroneurodiagnostic technology, and respiratory care
      educational programs. Currently, little is known about our educational capacity
      and the need for advanced degrees for sleep medicine technical support. METHODS:
      A questionnaire was developed about current and future community and educational
      needs for sleep technologists. The questionnaire was sent to directors of CAAHEP
      accredited polysomnography and electroneurodiagnostic technology programs
      (associate degree and certificate programs), and directors of CoARC-accredited
      respiratory therapy associate degree and bachelor degree programs (n = 358).
      Qualitative and quantitative data were collected via an internet survey tool.
      Data analysis was conducted with the IBM SPSS statistical package and included
      calculating means and standard deviations of the frequency of responses.
      Qualitative data was analyzed and classified based on emerging themes. RESULTS:
      One hundred seven of 408 program directors completed the survey. Seventy-four
      percent agreed that demand for qualified sleep technologists will increase, yet
      50% of those surveyed believe there are not enough educational programs to meet
      the demand. Seventy-eight percent of those surveyed agreed that the educational
      requirements for sleep technologists will soon increase; 79% of those surveyed
      believe sleep centers have a need for technologists with advanced training or
      specialization. CONCLUSIONS: Our study shows educators of associate and
      certificate degree programs believe there is a need for a bachelor's degree in
      sleep science and technology.

PMID- 24127154
TI  - Bears and bubbles: prognosticating the future of sleep technologists.

PMID- 24127155
TI  - Improvement of restless legs syndrome by varenicline as antismoking treatment.
AB  - Varenicline is a partial agonist at the alpha4beta2 nicotinic acetylcholine
      receptor effective as smoking cessation pharmacotherapy. We present a familial
      case of severe restless legs syndrome (RLS) resistant to polytherapy who showed a
      consistent and effective amelioration of RLS symptoms after introduction of
      varenicline as antismoking drug.

PMID- 24127156
TI  - "Nocturnal seizures" in idiopathic pulmonary arterial hypertension.
AB  - The usual differential diagnoses of nocturnal events in children include
      parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic
      jerks, periodic limb movements of sleep, and sleep disordered breathing. We
      report a previously healthy young girl who presented to the sleep clinic for
      evaluation of nocturnal events which were diagnosed as medically refractory
      nocturnal seizures. It was not until a syncopal event occurred in the daytime,
      which prompted referral for cardiac evaluation, the diagnosis of idiopathic
      pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should
      consider IPAH in the differential diagnosis of nocturnal events in children.

PMID- 24127157
TI  - Master's-level practitioners as cognitive behavioral therapy for insomnia
      providers: an underutilized resource.
AB  - Despite the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in
      treating chronic insomnia, it remains underutilized. Lack of appropriately
      trained CBT-I providers is a major reason. Master's-level practitioners (MLPs)
      may, in addition to doctoral-level psychologists, be uniquely positioned to fill
      this role, based not only on "goodness of professional fit" but also given a
      handful of studies showing these individuals' care outcomes meet or exceed
      standard outcomes. However, the ability of MLPs to provide CBT-I will be
      significantly restricted until a clear pathway is established that extends from
      training opportunities to credentialing. Further questions remain about how to
      attract and incorporate MLPs into established practices.

PMID- 24127158
TI  - A patient with intractable attacks of cataplexy.

PMID- 24127159
TI  - Sex-biased weaning and early childhood diet among middle holocene hunter
      gatherers in Central California.
AB  - This article evaluates age of weaning and early childhood diets of eight males
      and nine females from a Middle Holocene (4300-3000 BP) site in Central
      California, CA-CCO-548. All individuals died as adults. delta(15) N values from
      serial sections of dentin collagen in first molars suggest females were fully
      weaned, on average, by 3.6 years of age, about 0.4 years later than males in the
      sample, suggesting possible greater parental investment in female offspring.
      However, throughout childhood females consumed lower trophic-level foods than
      males. This could indicate greater investment in males through provisioning of
      higher quality foods, or alternatively, some degree of independent foraging by
      males starting as early as 2 to 3 years of age. Even as adults, these same males
      and females consumed a different range of foods as indicated by their bone
      collagen delta(13) C and delta(15) N values. Overall, the data suggest children
      were enculturated early into their respective gendered diets, with girls
      consuming greater amounts of plant foods and boys consuming greater amounts of
      higher-trophic level fish and meat protein.

PMID- 24127160
TI  - Xanthine oxido-reductase, free radicals and cardiovascular disease. A critical
      review.
AB  - Free radical mediated pathologies occupy a special place in medical semiology and
      in mechanistic interpretation of diseases. Free radicals, or better reactive
      oxygen species (ROS) or reactive nitrogen species (RNS) play also an important
      role in cell signaling. This is the basis of the ambivalent (Jekyll-Hyde)
      situation of ROS in biology and pathology. Aging itself is attributed by a
      popular theory to free radicals. A number of ROS-scavenging substances and
      procedures were described without however reaching credibility for their
      therapeutic value. An interesting exception is the xanthine oxido-reductase
      produced ROS and their role in cardiovascular disease. Allopurinol inhibition of
      xanthine oxido-reductase was shown to be efficient in some cases of
      cardiovascular diseases. Another important aspect of xanthine oxido-reductase
      produced ROS is their antibacterial capacity considered to be of importance with
      newborns fed on milk rich in this enzyme as well as at the gastrointestinal
      barrier. This ambivalent role of xanthine oxido-reductase justifies this review
      on the basic enzymatic mechanisms involved, derived ROS production, their role in
      the above mentioned biological processes and especially the interest of the
      inhibition of this enzyme as a preventive or curative measure in some
      cardiovascular pathologies.

PMID- 24127162
TI  - Mutations in CDKN2C (p18) and CDKN2D (p19) may cause sporadic parathyroid
      adenoma.

PMID- 24127161
TI  - Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral
      stimulated Raman scattering microscopy.
AB  - A finger on the pulse: Current molecular analysis of cells and tissues routinely
      relies on separation, enrichment, and subsequent measurements by various assays.
      Now, a platform of hyperspectral stimulated Raman scattering microscopy has been
      developed for the fast, quantitative, and label-free imaging of biomolecules in
      intact tissues using spectroscopic fingerprints as the contrast mechanism. 

PMID- 24127163
TI  - Treatment of spider veins of the lower extremity with a novel 532 nm KTP laser.
AB  - BACKGROUND AND OBJECTIVES: This study investigated a novel, high-power, 532 nm
      frequency-doubled Nd:YAG, KTP laser with contact cooling for the treatment of
      spider veins of the lower extremities. STUDY: Twenty female subjects with
      Fitzpatrick skin types I-III, were treated to 79 sites using the 532 nm
      wavelength of a dual-wavelength 532/1,064 nm laser (Excel V, Cutera, Brisbane,
      CA) with a 5 mm-diameter spot, fluences ranging from 13 to 15 J/cm(2) , and a
      pulse-duration of 40 milliseconds. Two treatments were performed 12 weeks apart.
      Photographs were taken at baseline and 12 weeks following the final treatment.
      Improvement was assessed by two independent physicians reviewing photographs in a
      blinded fashion using a 5-point improvement scale. RESULTS: All subjects
      demonstrated improvement resulting in a median improvement of 2.5 (one-sample
      Wilcoxon signed rank test, 95% CI: 1.9-2.9, P = 0.000). The reviewers were highly
      consistent (kappa of 0.85), and highly accurate (kappa of 0.85) in identification
      of "after photograph" and they were highly consistent in grading improvement.
      Subjects and the treating physician reported "significant" to "very significant"
      (~51 to 100%) improvement in 75% and 69% of subjects, respectively. Post
      inflammatory hyper-pigmentation was seen in 2% of sites (1/64). No serious
      adverse effects reported. All subjects tolerated the treatments well (mean pain
      score of 2.9/10). CONCLUSION: Treatment of spider veins of the leg with a novel
      532 nm KTP laser was found to be safe and effective, with minimal discomfort and
      adverse effects in Fitzpatrick skin types I-III.

PMID- 24127164
TI  - Using self-management to improve the reciprocal social conversation of children
      with autism spectrum disorder.
AB  - Individuals with autism spectrum disorders often exhibit difficulties with
      reciprocal social conversation, engaging in limited verbal exchanges, even when
      language structures are intact. This study employed a multiple baseline design to
      examine the effectiveness of a self-management intervention targeting (1) on
      topic responsiveness to a conversational partner; (2) expansion of the
      conversational topic; and (3) on-topic question asking. Results demonstrated
      improved reciprocal social conversation through elaborated responses and on-topic
      question asking, which generalized and maintained. Social validity measures by
      naive observers indicated that the intervention led to meaningful improvements
      during conversation, including interest, naturalness, and desirability as a
      conversational partner. 

PMID- 24127166
TI  - Symptoms of autism among children with congenital deafblindness.
AB  - Associations between congenital deafness or blindness and autism have been found.
      The main consequences of congenital sensory impairment, being barriers for
      communication, language and social interaction development, may lead to symptoms
      of autism. To date only few studies have been reported concerning individuals
      with congenital deafblindness. This study examines symptoms of autism among 71
      children with congenital deafblindness using the Autism Behavior Checklist. The
      cohort of children with congenital deafblindness was found to have symptoms of
      autism on a level similar to children with another developmental disorder than
      autism for example intellectual disability. No association was found between
      severity of congenital sensory impairment and severity or type of symptoms of
      autism. 

PMID- 24127165
TI  - Use of transcranial magnetic stimulation in autism spectrum disorders.
AB  - The clinical, social and financial burden of autism spectrum disorder (ASD) is
      staggering. We urgently need valid and reliable biomarkers for diagnosis and
      effective treatments targeting the often debilitating symptoms. Transcranial
      magnetic stimulation (TMS) is beginning to be used by a number of centers
      worldwide and may represent a novel technique with both diagnostic and
      therapeutic potential. Here we critically review the current scientific evidence
      for the use of TMS in ASD. Though preliminary data suggests promise, there is
      simply not enough evidence yet to conclusively support the clinical widespread
      use of TMS in ASD, neither diagnostically nor therapeutically. Carefully designed
      and properly controlled clinical trials are warranted to evaluate the true
      potential of TMS in ASD. 

PMID- 24127167
TI  - Characteristics of mild dengue virus infection in Thai children.
AB  - A four-year longitudinal cohort and geographic cluster study in rural Thailand
      was conducted to characterize the clinical spectrum of dengue virus (DENV)
      infection. Symptomatic DENV infections in the cohort were detected by active
      school absence-based surveillance that triggered cluster investigations around
      ill cohort children. Data from 189 cohort children with symptomatic DENV
      infection and 126 contact children in the clusters with DENV infection were
      analyzed. Of infected contacts, only 19% were asymptomatic; 81% were symptomatic,
      but only 65.9% reported fever. Symptom-based case definitions were unreliable for
      diagnosis. Symptomatic infections in contacts were milder with lower DENV RNA
      levels than the cohort. Infections in contacts with fever history were more
      likely to have detectable DENV RNA than infections without fever history. Mild
      infections identified by cluster investigations account for a major proportion of
      all DENV infections. These findings are relevant for disease burden assessments,
      transmission modeling, and determination of vaccine impact.

PMID- 24127168
TI  - Primary prophylaxis of disseminated histoplasmosis in HIV patients in French
      Guiana: arguments for cost effectiveness.
AB  - Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS)
      and AIDS-related deaths in French Guiana. Cohort data were used to determine
      whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts
      < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12%
      of patients died, 60% were aware of their human immunodeficiency virus (HIV)
      infection and adherence was only 50%, primary prophylaxis would prevent 1 death
      and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533
      per life-year saved, 4,415 Euros per averted case, when only counting the costs
      of itraconazole prophylaxis. Taking into account the total costs of
      hospitalization showed that primary prophylaxis would allow a savings of 185,178
      Euros per year. Even in a scenario of low adherence, primary prophylaxis would be
      cost-effective in French Guiana, and presumably in the rest of the Guianas and
      the Amazon.

PMID- 24127169
TI  - Apoptosis in larval and frog skin of Rana pipiens, R. catesbeiana, and
      Ceratophrys ornata.
AB  - Apoptosis (programmed cell death) occurs during normal development of anurans in
      organs such as gills, gut, and tail. For example, apoptotic cells have been
      reported in the luminal epithelium along the length of the digestive tract of
      both larvae and frogs; however, timing of the peak number of such cells varies in
      different species. The purpose of the present study was to ascertain whether
      apoptosis also varies by species during metamorphic restructuring of the skin (as
      larval epithelium is replaced by adult epidermis). To determine this, cross
      sections of dorsal skin from representative larval stages and frogs of Rana
      pipiens, R. catesbeiana, and Ceratophrys ornata were incubated with monoclonal
      antibody against active caspase-3, one of the main enzymes in the apoptotic
      cascade. We observed apoptotic cells in the epidermis of the skin of the three
      species and found that such cells were more numerous in larval stages than in
      frogs and more abundant in the two ranid species than in C. ornata. These results
      contribute to our understanding of metamorphic changes in anuran skin.

PMID- 24127170
TI  - Bemiparin versus unfractionated heparin as bridging therapy in the perioperative
      management of patients on vitamin K antagonists: the BERTA study.
AB  - BACKGROUND AND OBJECTIVE: The management of patients on vitamin K antagonist
      therapy who require an invasive procedure is problematic. A randomised,
      controlled, double-blind clinical trial was designed to compare the efficacy and
      safety of bemiparin, a low molecular weight heparin (LMWH), with unfractionated
      heparin (UFH) as bridging therapy: the BERTA (BEmiparin Randomised Trial on
      bridging Anticoagulants) study. METHODS: Two hundred and six patients on long
      term oral anticoagulation therapy (OAT) requiring an invasive procedure were
      randomized to receive bridging therapy with bemiparin + matching placebo or UFH.
      OAT was resumed on day 1. The study medication was continued for 5-6 days after
      the procedure. The primary efficacy endpoint was the combined incidence of
      arterial and venous thromboembolic events. The primary safety endpoint was the
      incidence of major bleeding within 10 days after the invasive procedure. RESULTS:
      There were no thromboembolic events in the bemiparin group, but two events (2.2
      %) occurred in the UFH group. No major bleeding occurred in either group, but
      minor bleeding occurred in four patients (4.3 %) and six patients (6.1 %) in the
      bemiparin and UHF groups, respectively. No deaths and no cases of severe
      thrombocytopenia occurred during the whole study period. CONCLUSION: Despite its
      small size, the BERTA study is the first randomised, double-blind clinical trial
      comparing UFH with a fixed high-risk thromboprophylactic dose of an LMWH as
      bridging therapy. There were no thromboembolic events and fewer bleeding episodes
      in the bemiparin group than in the UFH group, hence we suggest that bemiparin is
      at least as safe as UFH as bridging therapy.

PMID- 24127172
TI  - Repeatability of diffusion-weighted imaging in rectal cancer.
AB  - PURPOSE: Serial diffusion-weighted MRI (DW-MRI) measurements of the apparent
      diffusion coefficient (ADC) of rectal tumors are used for rectal cancer response
      evaluation after neo-adjuvant treatment. In this study, we determined the
      repeatability of DW-MRI to distinguish therapy-related response from measurement
      variations. MATERIALS AND METHODS: In 18 patients with rectal cancer on five
      consecutive days, 1.5 Tesla (T) MR imaging was performed including two identical
      DW-MRI sequences. The repeatability of the tumor ADC measurements and the
      intraobserver ADC variation were depicted in a Bland-Altman plot. The
      repeatability coefficient was calculated as the range of ADC values of two
      identical DWI measurements for 95% of subjects. It was expressed as percentage of
      the mean ADC value. RESULTS: Three females and 15 males were included. The mean
      tumor ADC value was 1.15 * 10(-3) mm(2)/s (SD 0.07 * 10(-3) mm(2)). The
      repeatability coefficient of the ADC value was 9.8% and for the intraobserver
      repeatability 4.7%. CONCLUSION: In serial DW-MRI for rectal cancer treatment
      response evaluation, a repeatability coefficient of 9.8% has to be considered to
      account for measurement variations in rectal tumor ADC. These variations
      represent observer judgement and patient and MR spectrometer induced variations.

PMID- 24127171
TI  - Probiotic-fermented purple sweet potato yogurt activates compensatory IGF
      IR/PI3K/Akt survival pathways and attenuates cardiac apoptosis in the hearts of
      spontaneously hypertensive rats.
AB  - Apoptosis is recognized as a predictor of adverse outcomes in subjects with
      cardiac diseases. The aim of this study was to explore the effects of probiotic
      fermented purple sweet potato yogurt (PSPY) with high gamma-aminobutyric acid
      (GABA) content on cardiac apoptosis in spontaneously hypertensive rat (SHR)
      hearts. The rats were orally adminsitered with 2 different concentrations of PSPY
      (10 and 100%) or captopril, 15.6 mg/kg, body weight (BW)/day. The control group
      was administered distilled water. DAPI and TUNEL staining were used to detect the
      numbers of apoptotic cells. A decrease in the number of TUNEL-positive cardiac
      myocytes was observed in the SHR-PSPY (10 and 100%) groups. In addition, the
      levels of key components of the Fas receptor- and mitochondrial-dependent
      apoptotic pathways were determined by western blot analysis. The results revealed
      that the levels of the key components of the Fas receptor- and mitochondrial
      dependent apoptotic pathway were significantly decreased in the SHR-captopril,
      and 10 and 100% PSPY groups. Additionally, the levels of phosphorylated insulin
      like growth factor-I receptor (p-IGF-IR) were increased in SHR hearts from the
      SHR-control group; however, no recovery in the levels of downstream signaling
      components was observed. In addition, the levels of components of the
      compensatory IGF-IR-dependent survival pathway (p-PI3K and p-Akt) were all highly
      enhanced in the left ventricles in the hearts form the SHR-10 and 100% PSPY
      groups. Therefore, the oral administration of PSPY may attenuate cardiomyocyte
      apoptosis in SHR hearts by activating IGF-IR-dependent survival signaling
      pathways. 

PMID- 24127175
TI  - Effectiveness of classroom response systems within an active learning
      environment.
AB  - In nursing education, the inclusion of pedagogical tools is necessary to
      transform Millennial classrooms. One such pedagogical tool currently offered is
      classroom response systems (CRS). The purpose of this study was to evaluate the
      effectiveness of CRS as a pedagogical tool in improving nursing students'
      examination performance within an active learning environment. A pretest-posttest
      design was used to determine whether there was a relationship between the use of
      CRS (independent variable) and nursing students' examination performance in a
      first-year Professional Practice course (dependent variable). Paired t tests
      revealed no greater improvement in posttest scores. Therefore, the use of CRS
      technology was not effective in increasing nursing students' examination scores
      in the Professional Practice course. Additional research is needed to provide
      adequate understanding of the effectiveness of CRS within the nursing education
      classroom.

PMID- 24127173
TI  - Novel genetic models of osteoporosis by overexpression of human RANKL in
      transgenic mice.
AB  - Receptor activator of NF-kappaB ligand (RANKL) plays a key role in osteoclast
      induced bone resorption across a range of degenerative bone diseases, and its
      specific inhibition has been recently approved as a treatment for women with
      postmenopausal osteoporosis at high or increased risk of fracture in the United
      States and globally. In the present study, we generated transgenic mice
      (TghuRANKL) carrying the human RANKL (huRANKL) genomic region and achieved a
      physiologically relevant pattern of RANKL overexpression in order to establish
      novel genetic models for assessing skeletal and extraskeletal pathologies
      associated with excessive RANKL and for testing clinical therapeutic candidates
      that inhibit human RANKL. TghuRANKL mice of both sexes developed early-onset bone
      loss, and the levels of huRANKL expression were correlated with bone resorption
      and disease severity. Low copy Tg5516 mice expressing huRANKL at low levels
      displayed a mild osteoporotic phenotype as shown by trabecular bone loss and
      reduced biomechanical properties. Notably, overexpression of huRANKL, in the
      medium copy Tg5519 line, resulted in severe early-onset osteoporosis
      characterized by lack of trabecular bone, destruction of the growth plate,
      increased osteoclastogenesis, bone marrow adiposity, increased bone remodeling,
      and severe cortical bone porosity accompanied by decreased bone strength. An even
      more severe skeletal phenotype developed in the high copy Tg5520 founder with
      extensive soft tissue calcification. Model validation was further established by
      evidence that denosumab, an antibody that inhibits human but not murine RANKL,
      fully corrected the hyper-resorptive and osteoporotic phenotypes of Tg5519 mice.
      Furthermore, overexpression of huRANKL rescued osteopetrotic phenotypes of RANKL
      defective mice. These novel huRANKL transgenic models of osteoporosis represent
      an important advance for understanding the pathogenesis and treatment of high
      turnover bone diseases and other disease states caused by excessive RANKL.

PMID- 24127176
TI  - Professional writing in nursing education: creating an academic-community writing
      center.
AB  - Contemporary professional nursing requires competency in both oral and written
      communication. Outside of writing for publication, instructional methods to teach
      professional writing in baccalaureate nursing programs are not well documented in
      the literature. The need for professional writing, coupled with the need to
      diversify the workforce with students from varying ethnic and educational
      backgrounds, creates some additional challenges to meet programmatic requirements
      for scholarly, evidence-based writing outcomes. As two new prelicensure programs
      were initiated, a comprehensive assessment was conducted that included student
      focus groups and writing assessment tools to assess writing quality and student
      support needs. As a result of these data, faculty implemented curricular and
      instructional revisions and created a writing center that was staffed by older
      adult volunteers who had careers in writing. The processes, tools, and
      preliminary outcomes of these faculty-initiated changes to improve student
      support for writing are presented.

PMID- 24127177
TI  - Principles and practices of social entrepreneurship for nursing.
AB  - Although social justice and action for change are among the nursing profession's
      core values, curricular content on social entrepreneurship for nurses is not as
      well developed as it is in the educational programs for students in business,
      engineering, or public policy. This article describes an undergraduate honors
      elective course in social entrepreneurship offered at New York University College
      of Nursing. The course uses a seminar format and incorporates content from the
      humanities, business, and service-learning, with the goal of promoting
      participants' understanding of the sources of inequality in the United States and
      providing the requisite skills to promote effective nursing action for social
      change.

PMID- 24127178
TI  - Alexithymia and burnout in nursing students.
AB  - Although previous studies have indicated an association between alexithymia and
      burnout, they have not controlled for well-established organizational factors,
      depression, and coping mechanisms that could confound the relationship. This
      study investigated the association between alexithymia and occupational burnout.
      One hundred eighty-three nursing students were assessed up to 3 months before
      graduating from their program. Alexithymia was measured with the Toronto
      Alexithymia Scale, occupational burnout was measured with the Maslach Burnout
      Inventory, work-related factors were measured with the Areas of Worklife Survey,
      depression was measured with Beck Depression Inventory-II, and coping strategies
      were measured with the COPE Dispositional Inventory. Hierarchical multiple
      regressions indicated that externally oriented thinking style was significantly
      associated with personal accomplishment and depersonalization after adjusting for
      depression, coping, and work-related factors. The results indicate that only a
      single aspect of the alexithymia construct serves as a possibly independent
      predisposing factor for specific burnout dimensions.

PMID- 24127179
TI  - Comparison of second-degree and traditional undergraduate nursing students' sense
      of belonging during clinical placements.
AB  - Second-degree undergraduate nursing programs are proliferating throughout Canada.
      Although these shorter programs are attracting students from a variety of
      disciplines and professions, a sense of belonging and the meaning or implications
      of belongingness have not been examined for this unique nursing student cohort. A
      survey design, using the Belongingness Scale-Clinical Placement Experience
      questionnaire, explores second-degree nursing students' sense of belonging,
      compared with that of 4-year undergraduate nursing students. Overall, second
      degree nursing students experienced a sense of belonging during clinical
      placements to a lesser degree than their counterparts in a traditional nursing
      program. Providing second-degree students with opportunities to know and create
      partnerships with nurse educators and staff while on placements, as well as
      providing them with feedback presented in positive terms, will help these
      students flourish and engender a greater sense of belonging.

PMID- 24127180
TI  - Promoting therapeutic communication and patient-centered care using standardized
      patients.
AB  - This article describes an assignment designed to incorporate the Quality and
      Safety Education for Nurses (QSEN) competency of patient-centered care into a
      simulation activity aimed to improve therapeutic communication skills in
      psychiatric nursing. During this pilot activity, students engaged in an
      interaction with an actor trained to portray an individual with mental illness.
      Students viewed their video-recorded interaction to identify communication
      techniques used and completed a self-evaluation examining their strengths and
      areas for improvement. Faculty and actors provided feedback to students during a
      faculty-led debriefing held to discuss the use of therapeutic communication and
      care focused on the knowledge, skills, and attitudes necessary to provide quality
      patient-centered care. Desired learning outcomes included the demonstration of
      therapeutic communication and assessment skills, empathy and caring, and
      addressing patient values, preferences, and beliefs.

PMID- 24127181
TI  - Evaluating dedicated education units for clinical education quality.
AB  - Dedicated education units (DEUs) have emerged as an important clinical education
      innovation within academic practice partnerships. However, rigorous evaluation
      has not been conducted previously. This article presents findings from a
      randomized, controlled, multiyear, multisite study comparing the clinical
      education quality for students educated in either the DEU innovation or
      traditional clinical education model within the same nursing course. The
      evaluation occurred within a larger study focusing on teaching capacity, faculty
      work life, and educational quality at one large, urban university collaborating
      with three agency partners. To examine learning outcomes, the question posed was,
      "In what ways, if any, does the DEU intervention, when compared to traditional
      clinical education, enhance educational quality?" Results indicate that
      educational quality and learning gains are significantly more positive for
      students clinically instructed in DEUs. Findings will be of interest to education
      and practice leaders seeking to enhance the quality of clinical teaching,
      learning, and nursing practice.

PMID- 24127182
TI  - Service-learning in baccalaureate nursing education: a literature review.
AB  - Service-learning is an educational pedagogy that provides students with an
      opportunity to apply classroom learning to real-world situations, while meeting a
      specific community need. The purpose of this literature review is to identify
      what type of baccalaureate nursing courses utilize service-learning, to determine
      the level at which baccalaureate nursing students are being engaged in service
      learning, and to evaluate the efficacy of service-learning to meet curricular
      objectives. Suggestions are made for instructors who are considering integrating
      service-learning into their curriculum.

PMID- 24127183
TI  - Metachronous cancer following Hartman procedure for obstructing sigmoid cancer:
      don't forget the rectal stump!

PMID- 24127184
TI  - Treatment with anti-tumor necrosis factor biologic agents in human T lymphotropic
      virus type I-positive patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the response to and safety of anti-tumor necrosis
      factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)-positive
      patients with rheumatoid arthritis (RA). METHODS: Therapeutic response was
      evaluated in 10 HTLV-I-positive and 20 HTLV-I-negative patients with RA (sex and
      age matched) at 3 months after the beginning of anti-TNF therapy using the
      European League Against Rheumatism improvement criteria. As secondary end points,
      the discontinuation rate of anti-TNF therapy and its safety, especially the
      development of adult T cell leukemia (ATL), were evaluated over a 2-year period.
      RESULTS: Significantly higher baseline levels of C-reactive protein (CRP) were
      observed in HTLV-I-positive patients than in HTLV-I-negative patients (P =
      0.0003). The response rate to anti-TNF therapy was lower in HTLV-I-positive
      patients than in HTLV-I-negative patients. The median CRP level, erythrocyte
      sedimentation rate, and Disease Activity Score in 28 joints at 3 months after
      anti-TNF treatment in HTLV-I-positive patients were significantly higher than in
      HTLV-I- negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The
      discontinuation rate due to insufficient response was significantly higher in
      HTLV-I-positive patients than in HTLV-I-negative patients (P = 0.013). During the
      2-year observation period, no patients developed ATL. CONCLUSION: These data
      suggest that HTLV-I-positive patients with RA had higher inflammation and greater
      resistance to anti-TNF treatment than HTLV-I-negative patients. Further study is
      necessary to determine whether HTLV-I infection should be measured when anti-TNF
      agents are administered to patients with RA, especially in areas were HTLV-I is
      endemic.

PMID- 24127186
TI  - Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects
      from tumor progression and metastasis.
AB  - Proteolytic maturation of various precursor proteins by the proprotein convertase
      Furin is now considered as a crucial step in tumor progression and metastasis.
      Here, we report the repression of the malignant and metastatic potential of
      carcinoma cells by the prodomain region of Furin (ppFurin), a naturally occurring
      inhibitor of this convertase. Overexpression of ppFurin in carcinoma cells in a
      stable manner significantly reduced their convertase activity and ability to
      mediate processing of the Furin cancer-related substrates platelet-derived growth
      factor (PDGF)-A and insulin-like growth factor-I receptor precursors. Unprocessed
      platelet-derived growth factor-A produced by ppFurin expressing cells failed to
      induce the activation of Akt in the platelet-derived growth factor receptor
      expressing cells NIH BALB/c-3T3 and treatment of ppFurin expressing cells with
      insulin-like growth factor-I failed to induce Akt phosphorylation, compared with
      controls. The malignant potential of ppFurin expressing cells was significantly
      reduced as revealed by the loss of anchorage-independent growth and survival that
      associated their increased chemosensitivity. In vivo, comparative studies
      revealed that expression of ppFurin in the carcinoma cells MDA-MB-231 and CT-26
      cells inhibited tumor growth when subcutaneously inoculated in nude mice. The use
      of an experimental liver colorectal metastasis model revealed the reduced ability
      of metastatic carcinoma CT-26 cells to colonize the liver in response to
      intrasplenic/portal inoculation. Further analyses revealed reduced Furin activity
      in tumors derived from intrasplenic inoculated mice with ppFurin expressing CT-26
      cells. This finding highlights the role of Furin in the malignant and metastatic
      potential of tumor cells and suggests the possible consideration of using its
      naturally occurring inhibitor ppFurin in anticancer therapy.

PMID- 24127185
TI  - "Unresectable" vulval cancers: is neoadjuvant chemotherapy the way forward?
AB  - Squamous cell carcinoma of the vulva is an uncommon gynaecological malignancy,
      but the incidence is increasing. A significant proportion of patients present
      with locally advanced disease, and management can prove challenging because of
      the size and/or location of the tumour. Surgery forms the mainstay of treatment,
      but the role of neoadjuvant therapy in minimizing morbidity is under
      investigation. Although chemotherapy alone has been largely neglected in favour
      of chemoradiotherapy, concerns about the toxicity of trimodality therapy and
      suboptimal results, particularly in node-positive patients, have led to renewed
      interest in neoadjuvant chemotherapy (NACT). A review of the available literature
      illustrates that NACT can produce dramatic responses, but operability rates and
      overall survival differ widely. The effect is dependent on as yet unidentified
      factors, although we speculate that age and tumour biology are important. Further
      work is required to delineate the optimal NACT regimen and the patient
      population(s) most likely to benefit from this practice. 

PMID- 24127187
TI  - Genome-wide analysis associates familial colorectal cancer with increases in copy
      number variations and a rare structural variation at 12p12.3.
AB  - Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a
      large number of genetic risk factors involved in CRC have not been understood.
      Copy number variations (CNVs) might partly contribute to the 'missing
      heritability' of CRC. An increased overall burden of CNV has been identified in
      several complex diseases, whereas the association between the overall CNV burden
      and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs
      on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the
      Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial
      CRC patients compared with healthy controls, especially for CNVs larger than 50kb
      (case/control ratio = 1.66, P = 0.025). In addition, we discovered for the first
      time a novel structural variation at 12p12.3 and determined the breakpoints by
      strategic PCR and sequencing. This 12p12.3 structural variation was found in four
      of 2862 CRC cases but not in 6243 healthy controls (P = 0.0098). RERGL gene
      (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation,
      sharing most of the conserved regions with its close family member RERG tumor
      suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a
      novel CRC-related gene. In conclusion, this is the first study to reveal the
      contribution of the overall burden of CNVs to familial CRC risk and identify a
      novel rare structural variation at 12p12.3 containing RERGL gene to be associated
      with CRC. 

PMID- 24127189
TI  - West Nile virus introduction into the New World.

PMID- 24127190
TI  - Brainstem PML lesion mimicking MS plaque in a natalizumab-treated MS patient.

PMID- 24127188
TI  - PrPc is temporospatially expressed in molar development of rats.
AB  - Odontogenesis, tooth development, is derived from two tissue components: ectoderm
      and neural crest-derived mesenchyme. Cyto-differentiation of odontogenic cells
      during development involves time-dependent and sequential regulation of genetic
      programs. This study was conducted to detect molecules implicated in cyto
      differentiation of developing molar germs of rats. Differential display-PCR
      revealed that PrP(c) was differentially expressed between cap/early bell-staged
      germs (maxillary 3rd molar germs) and root formation-staged germs (maxillary 2nd
      molar germs) at postnatal day 9. Both levels of PrP(c) mRNA and protein
      expression were higher in the root formation stage than the cap/early bell stage
      and increased in a time-dependent manner. Immunofluorescence revealed for the
      first time that PrP(c) was not localized in the enamel organ, but localized in
      dental follicular cells for the development of the periodontal ligament and
      cementum as well as odontoblasts, both of which are of neural crest origin. These
      results suggest that the physiological functions of the PrP(c) in tooth
      development may be implicated in the differentiation of neural crest-derived
      mesenchyme including the periodontal tissues for root formation rather than
      epithelial tissue.

PMID- 24127191
TI  - Right brain: how to treat the untreatable.

PMID- 24127192
TI  - Evidence-based guideline: Treatment of parenchymal neurocysticercosis: report of
      the Guideline Development Subcommittee of the American Academy of Neurology.

PMID- 24127193
TI  - Teaching neuroimages: FDG-PET imaging in primary diffuse leptomeningeal
      gliomatosis.

PMID- 24127194
TI  - Teaching neuroimages: ectopic posterior pituitary.

PMID- 24127195
TI  - Long-term efficacy of linear-scanning 808 nm diode laser for hair removal
      compared to a scanned alexandrite laser.
AB  - BACKGROUND AND OBJECTIVE: Alexandrite and diode lasers are commonly used for hair
      removal. To date, the available spot sizes and repetition rates are defining
      factors in terms of penetration depth, treatment speed, and efficacy. Still,
      larger treatment areas and faster systems are desirable. To compare the efficacy,
      tolerability, and subject satisfaction of a continuously linear-scanning 808 nm
      diode laser with an alexandrite 755 nm laser for axillary hair removal. STUDY
      DESIGN: A total of 31 adults with skin types I-IV received 6 treatments at 4-week
      intervals with a 755 nm alexandrite laser (right axilla) and a continuously
      linear-scanning 808 nm diode laser (left axilla). Axillary hair density was
      assessed using a computerized hair detection system. RESULTS: There was a
      significant reduction in axillary hair after the 6th treatment (P < 0.05) on both
      sides (left, 808 nm: hair clearance of 72.16%; right, 755 nm: hair clearance of
      71.30%). The difference in reduction between the two lasers was not significant,
      but both were persistant at 18 months follow-up (left: hair clearance of 73.71%;
      right: hair clearance of 71.90%). Erythema and perifollicular edema were more
      common after alexandrite laser treatment, but all side effects were transient.
      While 62.50% of patients reported more pain in response to treatment with the new
      diode laser, all patients rated treatment with either laser tolerable.
      CONCLUSION: Treatment with either the alexandrite or the linear-scanning diode
      laser results in significant, comparable, persistent (at least 18 months)
      axillary hair reduction among individuals with skin types I-IV.

PMID- 24127197
TI  - Interstitial deletion of 3p22.3p22.2 encompassing ARPP21 and CLASP2 is a
      potential pathogenic factor for a syndromic form of intellectual disability: a co
      morbidity model with additional copy number variations in a large family.
AB  - We describe a family in which four individuals (the mother and three children)
      presented with an overlapping phenotype of minor physical anomalies and
      intellectual disability. Four previously unreported copy number variants were
      found inherited either from the affected mother or from the healthy father,
      consisting of a 3p22.3p22.2 deletion (2.5 Mb), a 3p24.3 deletion (0.55 Mb), a
      6q22.31 duplication (0.74 Mb), all maternally inherited, and an 18q11.2
      duplication (0.276 Mb) which was paternally inherited. The deletions on
      chromosome 3 were both found to segregate with the disease. However, being the
      0.55 Mb deleted segment on 3p24.3 devoid of genes, we considered that the 2.5 Mb
      deletion on 3p22.3p22.2 acts as major pathogenic rearrangement in this condition.
      Among the transcribed genes residing in this interval, ARPP21 and CLASP2 are
      proposed as good candidate genes on the basis of their functional properties. A
      co-morbidity role for the other small rearrangements detected in the affected
      individuals in association with the 3p22.3p22.2 deletion is also suggested,
      according to a second-side model of pathogenesis.

PMID- 24127196
TI  - Arene C-H amination at nickel in terphenyl-diphosphine complexes with labile
      metal-arene interactions.
AB  - The meta-terphenyl diphosphine, m-P2, 1, was utilized to support Ni centers in
      the oxidation states 0, I, and II. A series of complexes bearing different
      substituents or ligands at Ni was prepared to investigate the dependence of metal
      arene interactions on oxidation state and substitution at the metal center.
      Complex (m-P2)Ni (2) shows strong Ni(0)-arene interactions involving the central
      arene ring of the terphenyl ligand both in solution and the solid state. These
      interactions are significantly less pronounced in Ni(0) complexes bearing L-type
      ligands (2-L: L=CH3CN, CO, Ph2CN2), Ni(I)X complexes (3-X: X=Cl, BF4, N3,
      N3B(C6F5)3), and [(m-P2)Ni(II)Cl2] (4). Complex 2 reacts with substrates, such as
      diphenyldiazoalkane, sulfur ylides (Ph2 S=CH2 ), organoazides (RN3: R=para
      C6H4OMe, para-C6H4CF3, 1-adamantyl), and N2O with the locus of observed
      reactivity dependent on the nature of the substrate. These reactions led to
      isolation of an eta(1)-diphenyldiazoalkane adduct (2-Ph2CN2), methylidene
      insertion into a Ni-P bond followed by rearrangement of a nickel-bound phosphorus
      ylide (5) to a benzylphosphine (6), Staudinger oxidation of the phosphine arms,
      and metal-mediated nitrene insertion into an arene C-H bond of 1, all derived
      from the same compound (2). Hydrogen-atom abstraction from a Ni(I)-amide (9) and
      the resulting nitrene transfer supports the viability of Ni-imide intermediates
      in the reaction of 1 with 1-azido-arenes.

PMID- 24127198
TI  - In vivo examination of the morphology of the tendinous inscription of the human
      semitendinosus muscle: gender and joint position effects.
AB  - A tendinous inscription divides the semitendinosus muscle in two parts and it may
      have an effect on its function. The purpose of this study was to determine the
      effects of joint position and gender on the tendinous inscription morphology.
      Ultrasonography scans were taken from 76 young males and females at rest, in nine
      combinations of hip and knee joint angles. The length of the tendinous
      inscription arms and the angles formed by the two arms (apex angle), the
      tendinous inscription with the superficial (surface angle), and deep (deep angle)
      aponeurosis were determined. The tendinous inscription was clearly visible in 70
      (out of 76) subjects. Analysis of variance designs showed that increasing hip
      flexion angle from 0 to 90 degrees  increased the long arm and muscle thickness
      but decreased the short tendinous inscription arm (P < 0.05). Changing knee
      flexion angle from 0 to 90 degrees  was accompanied by a longer tendinous
      inscription arm and an increased apex angle (P < 0.05). Long arm length and
      muscle thickness significantly increased from the shortest (hip 0 degrees  - knee
      90 degrees ) to the longest muscle lengths (hip 0 degrees  - knee 90 degrees ).
      Males had a significantly higher surface, apex, and deep angle and a lower
      normalized tendinous inscription long arm than females (P < 0.05). These results
      indicate that the effect of the tendinous inscription (if any) on semitendinous
      muscle function depends on hip and knee joint angle while it may be gender
      dependent.

PMID- 24127200
TI  - A phase 2 study of naproxen submicron particle capsules in patients with post
      surgical dental pain.
AB  - BACKGROUND: Naproxen is an NSAID with documented efficacy in pain management;
      however, it is associated with serious dose-related adverse events. A lower-dose
      naproxen drug product with comparable efficacy to commercially available naproxen
      could address these concerns. We studied the efficacy and safety of naproxen
      submicron particle capsules in patients with acute post-surgical dental pain.
      METHODS: A phase 2, multicenter, randomized, single-dose study (NCT01229228)
      enrolled 254 patients (18-34 years old) undergoing third molar extraction.
      Patients who experienced moderate-to-severe pain <=6 h following surgery received
      naproxen submicron particle capsules 200 or 400 mg, naproxen tablets 250 or 500
      mg, or placebo. The primary efficacy parameter was patient-reported total pain
      relief over 0-12 h following administration of study medication. Secondary
      efficacy parameters included patient-reported total pain relief over 0-4 and 0-8
      h; pain intensity assessments from 0 to 4, 0 to 8, and 0 to 12 h; and time to
      onset of analgesia. Safety and tolerability were also assessed. RESULTS: Naproxen
      submicron particle capsules 200 mg (25.9 +/- 2.0; 95% CI 21.9-29.8), naproxen
      tablets 250 mg (24.4 +/- 2.0; 95% CI 20.4-28.3), naproxen submicron particle
      capsules 400 mg (31.9 +/- 2.0; 95% CI 28.1-35.8), and naproxen tablets 500 mg
      (28.5 +/- 2.0; 95% CI 24.7-32.4) groups experienced greater pain relief over 12 h
      compared with placebo (P < 0.001). Similar trends were observed for secondary
      outcomes of total pain relief over 0-4, 0-8 h, and time to onset of analgesia.
      Adverse events were generally similar across all treatment groups. CONCLUSION:
      Lower-dose naproxen submicron particle capsules provided effective analgesia in
      acute post-surgical dental pain and warrant further evaluation as a potentially
      promising treatment for acute pain conditions.

PMID- 24127199
TI  - Proangiogenic microtemplated fibrin scaffolds containing aprotinin promote
      improved wound healing responses.
AB  - Survival of tissue engineered constructs after implantation depends heavily on
      induction of a vascular response in host tissue, promoting a quick anastomosis of
      the cellular graft. Additionally, implanted constructs typically induce fibrous
      capsule formation, effectively preventing graft integration with host tissue.
      Previously we described the development of a high density microtemplated fibrin
      scaffold for cardiac tissue engineering applications with tunable degradation and
      mechanical properties which promoted seeded cell survival and organization in
      vitro (Thomson et al., Tissue Eng Part A, 2013). Scaffold degradation in vitro
      was controllable by addition of the serine protease inhibitor aprotinin and/or
      the fibrin cross-linker Factor XIII (FXIII). The goal of this study was to assess
      host tissue responses to these fibrin scaffold formulations by determining
      effects on scaffold degradation, angiogenic responses, and fibrous capsule
      formation in a subcutaneous implant model. Aprotinin significantly decreased
      scaffold degradation over 2 weeks of implantation. A significant increase in
      capillary infiltration of aprotinin implants was found after 1 and 2 weeks, with
      a significantly greater amount of capillaries reaching the interior of aprotinin
      scaffolds. Interestingly, after 2 weeks the aprotinin scaffolds had a
      significantly thinner, yet apparently more cellular fibrous capsule than
      unmodified scaffolds. These results indicate aprotinin not only inhibits fibrin
      scaffold degradation, but also induces significant responses in the host tissue.
      These included an angiogenic response resulting in increased vascularization of
      the scaffold material over a relatively short period of time. In addition,
      aprotinin release from scaffolds may reduce fibrous capsule formation, which
      could help promote improved integration of cell-seeded scaffolds with host
      tissue. 

PMID- 24127202
TI  - Challenges in diagnosing Muckle-Wells syndrome: identifying two distinct
      phenotypes.
AB  - OBJECTIVE: The diagnosis of Muckle-Wells syndrome (MWS) remains challenging due
      to the clinical heterogeneity and lack of diagnostic criteria. The aims of this
      study were to describe key elements of the diagnostic evaluation process in MWS
      and compare identified variables between patients diagnosed in childhood and
      adulthood. METHODS: A cohort study of consecutive patients with a clinical and
      genetic diagnosis of MWS was conducted at 2 reference centers for
      autoinflammatory diseases. Demographic information, clinical presentation, access
      to care, and preclinical evaluation variables were captured. Presenting symptoms
      were compared between groups of patients diagnosed in childhood and adulthood.
      Prediction analysis explored variables associated with late diagnosis.
      Correspondence analysis identified clinical phenotypes. RESULTS: A total of 34
      MWS patients were included (16 males, 18 females) and median age at diagnosis was
      31.5 years (range 0.5-75 years). Patients diagnosed during childhood reported
      musculoskeletal symptoms (62%), rash (62%), fever (54%), and abdominal pain
      (31%). Those diagnosed as adults described musculoskeletal symptoms (86%), rash
      (67%), hearing loss (52%), and fatigue (29%). Hearing loss was associated with
      late diagnosis, while access-to-care variables were not predictive.
      Correspondence analysis identified distinct clinical phenotypes as follows: an
      "inflammatory phenotype" (most commonly seen in patients diagnosed in childhood
      and characterized by relapsing fever and abdominal pain), an intermediate
      phenotype, and an "organ-disease" phenotype in patients diagnosed during
      adulthood and characterized by fatigue and hearing loss. CONCLUSION: Distinct
      clinical phenotypes were identified in patients with MWS. These are closely
      related to age at diagnosis. The presence of these phenotypes has to be
      considered when developing diagnostic criteria for MWS.

PMID- 24127203
TI  - P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated
      oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk
      HPV-infection in head and neck papillomas and laryngeal dysplasias.
AB  - Human papillomavirus (HPV) is a risk factor for the development of benign and
      malignant mucosal head and neck lesions. P16(INK4A) is often used as a surrogate
      marker for HPV-infection, although there is still controversy with respect its
      reliability. Our aim was to determine if p16(INK4A) overexpression can accurately
      predict both high-risk and low-risk-HPV-presence in (pre)malignant and benign
      head and neck lesions. P16(INK4A) immunohistochemistry was performed on paraffin
      embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC),
      14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal
      papillomas. PCR, enzyme-immunoassay and FISH analysis were used to assess HPV
      presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10
      (71%) were HPV16-positive, respectively. All tonsillar papillomas were HPV
      negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive
      for HPV6 or -11. P16(INK4A) immunohistochemistry revealed a strong nuclear and
      cytoplasmic staining in 50 out of 51 HPV16-positive and 5 out of 111 HPV-negative
      OPSCC (p < 0.0001) and in all HPV16-positive tonsillar dysplasias, whereas highly
      variable staining patterns were detected in the papillomas and laryngeal
      dysplasias, irrespective of the HPV-status. In addition, the latter lesions
      generally showed a higher nuclear than cytoplasmic p16(INK4A) immunostaining
      intensity. In conclusion, our data show that strong nuclear and cytoplasmic
      p16(INK4A) overexpression is a reliable surrogate indicator for HPV16 in OPSCC
      and (adjacent) dysplasias. For HPV6 or -11-positive and HPV-negative benign and
      premalignant lesions of the tonsil and larynx, however, p16(INK4A) immunostaining
      is highly variable and cannot be recommended to predict HPV-presence.

PMID- 24127204
TI  - Dynamic contrast enhanced-MRI in rectal cancer: Inter- and intraobserver
      reproducibility and the effect of slice selection on pharmacokinetic analysis.
AB  - PURPOSE: To assess inter- and intraobserver reproducibility of DCE-MRI
      measurements and possible differences between two directly adjacent slices.
      MATERIALS AND METHODS: DCE-MRI measurements of 30 patients with histologically
      proven rectal carcinoma were performed on a 1.5 Tesla (T) MR system during
      intravenous contrast agent application before and after neoadjuvant
      radiochemotherapy with two directly adjacent slices used for calculation per
      patient. Images were analyzed semiquantitatively (parameters TTP and MITR) and
      quantitatively using the Brix compartment model (parameters kep and A) by two
      different observers and at two different time points. The concordance correlation
      coefficient was calculated for every parameter in intra-/interobserver comparison
      and slice comparison. RESULTS: Median relative differences below 10% for all
      parameters and high values of the concordance correlation coefficient (CCC) were
      found for most pharmacokinetic parameters in inter-/intraobserver comparison and
      slice comparison, with the exception of the parameter A before therapy in intra-/
      interobserver comparison (CCC: 0.315/0.452) and kep before therapy in
      intraobserver comparison (CCC: 0.362). CONCLUSION: Our results indicate good
      inter- and intraobserver reproducibility for most pharmacokinetic parameters and
      for the two adjacent slices measured. However, as there were some parameters that
      demonstrated poor correlation, testing for reproducibility and a multiobserver
      approach might be considered whenever using pharmacokinetic parameters as
      biomarkers.

PMID- 24127205
TI  - Covalent attachment of porphyrins and ferrocenes to electrode surfaces through
      direct anodic oxidation of terminal ethynyl groups.
AB  - One with the surface: A method is presented for electrode modification with
      terminal alkynes and alkenes. Direct oxidation of these moieties leads to
      efficient grafting onto glassy carbon, gold, platinum, and indium tin oxide
      surfaces. Various ferrocenes and 5,10,15,20-(4-ethynylphenyl)porphyrin were
      attached in this way. 

PMID- 24127206
TI  - Physicochemical property of starch-pectin conjugates with resistance to enzymatic
      activity.
AB  - BACKGROUND: In view of the high nutritional values and bioactivities of resistant
      starch and pectin, it would be a good choice to chemically combine pectin and
      starch to give a new type of chemically modified resistant starch. RESULT: A new
      type of chemically modified resistant starch has been prepared by cross-linking
      starch and pectin using sodium trimetaphosphate. Starch-pectin conjugates can
      well prevent the hydrolysis catalysed by different enzymes, such as alpha
      amylase, amyloglucosidase, pancreatin as well as beta-amylase and glucosidase.
      Although the conjugates do not change the crystal type of starch, they increase
      the degree of crystallinity. Moreover, thermal stability and structural
      homogeneity of the conjugates are positively correlated with double-helical order
      in the crystalline region. CONCLUSION: This study gives a new method for the
      preparation of resistant starch-pectin conjugates which can be widely used as a
      new type of food additive in the industry.

PMID- 24127207
TI  - Evaluation of endobronchial ultrasound-guided fine-needle aspirations (EBUS-FNA):
      correlation with adequacy and histologic follow-up.
AB  - BACKGROUND: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) is
      a minimally invasive modality for diagnosing mediastinal lesions. When
      determining adequacy, EBUS-FNAs are evaluated for diagnostic material or
      sufficient lymphoid tissue. In this study, the authors evaluated their experience
      with EBUS-FNAs and correlated the findings with adequacy and histologic follow
      up. METHODS: EBUS-FNAs were retrospectively reviewed over a 3-year period and
      correlated with the clinicopathologic findings, adequacy, and histologic follow
      up. RESULTS: In total, 593 EBUS-FNAs were obtained from 356 patients, including
      420 (71%) satisfactory (SAT) cases, 107 (18%) less than optimal (LTO) cases, and
      66 (11%) unsatisfactory (UNSAT) cases. The overall diagnostic yield was 71%, and
      the mediastinal (N2) lymph nodes had better yield (72%) than the peripheral
      intrapulmonary and hilar (N1) lymph nodes (64%). Histologic follow-up was
      available in 203 cases (34%), and malignancy was identified in 7 UNSAT cases
      (23%), 6 LTO-negative cases (11%), and 4 SAT cases (3%) with a negative cytologic
      diagnosis. In the suboptimal cases with follow-up, 79% were benign and 21% were
      malignant on follow-up, including 25 (14%) with fibrosis or hyalinization. The
      sensitivity, specificity, and positive and negative predictive values in the
      study were 80%, 100%, 100%, and 95%, respectively. CONCLUSIONS: The current data
      demonstrated that EBUS-FNA has good sensitivity, high specificity, and a higher
      diagnostic yield for N2 lymph nodes compared with N1 lymph nodes. The data also
      illustrate the finding that suboptimal cases have a greater risk of false
      negative diagnoses and a 21% chance of malignancy, including processes with
      fibrosis or hyalinization.

PMID- 24127208
TI  - Silver-catalyzed hydrogenation of aldehydes in water.

PMID- 24127209
TI  - Clinical pharmacokinetics of clopidogrel and its metabolites in patients with
      cardiovascular diseases.
AB  - BACKGROUND AND OBJECTIVE: Approximately 5-40 % of patients treated with
      clopidogrel do not display an adequate antiplatelet response. Clopidogrel
      resistance may be caused by insufficient drug absorption or impaired metabolic
      activation of the drug. The aim of this study was to evaluate the
      pharmacokinetics of clopidogrel and its metabolites in plasma samples from
      patients treated with high and low doses of clopidogrel, to obtain a possible
      explanation for antiplatelet resistance. METHODS: The study included patients
      receiving either a single 300 mg loading dose of clopidogrel (n = 17) or a 75 mg
      dose (n = 45) for at least 7 days before sample collection. The concentrations of
      clopidogrel and its metabolites-the inactive H3 and the pharmacologically active
      H4 isomers of the thiol metabolite and the inactive carboxylic acid metabolite-in
      plasma samples (stabilized with 2-bromo-3'-methoxyacetophenone) from three
      patients after 300 mg and from 41 patients after 75 mg of the drug were
      determined using a validated high-performance liquid chromatography method with
      tandem mass spectrometry. The non-stabilized samples from the remaining patients
      were analysed using a validated capillary electrophoresis method. The calculated
      concentrations were used to determine the pharmacokinetic parameters of the
      analytes. The pharmacodynamic response to clopidogrel treatment, expressed as
      adenosine diphosphate-induced platelet aggregation, was measured using a
      Multiplate analyser. RESULTS: The pharmacokinetic parameter values for the H3 and
      H4 isomers determined in the studied group of patients treated with clopidogrel
      75 mg (maximum plasma concentration [C max] 5.29 +/- 5.54 and 7.13 +/- 6.32 ng/mL
      for H3 and H4, respectively; area under the plasma concentration-time curve from
      time zero to time t [AUC t ] 7.37 +/- 6.71 and 11.30 +/- 9.58 ng.h/mL for H3 and
      H4, respectively) were lower than those reported in healthy volunteers, according
      to the literature data. Platelet aggregation measured with a Multiplate analyser
      ranged between 37 and 747 AU.min. A significant correlation was found between the
      C max of the active H4 isomer and platelet aggregation (p = 0.025). CONCLUSION:
      The C max of the active H4 isomer and platelet aggregation measured by the
      Multiplate analyser may serve as markers of the patient response to clopidogrel
      therapy.

PMID- 24127210
TI  - Antimalarial drug resistance in Bangladesh, 1996-2012.
AB  - Malaria remains an important health problem in Bangladesh, with approximately 14
      million people at risk. Antimalarial drug resistance is a major obstacle to the
      control of malaria in endemic countries. In 2012, Bangladesh reported an
      estimated 29 522 malaria episodes, of which 94% were reported as being caused by
      Plasmodium falciparum. In this study, we reviewed and summarized antimalarial
      drug resistance data from Bangladesh published until June 2013. We searched
      published sources for data referring to any type of P. falciparum drug resistance
      (in vivo, in vitro, or molecular) and found 169 articles published in peer
      reviewed journals. Of these, 143 articles were excluded because they did not meet
      our inclusion criteria. After detailed review of the remaining 26 articles, 14
      were selected for evaluation. Published studies indicate that P. falciparum shows
      varying levels of resistance to chloroquine, mefloquine and sulfadoxine
      pyrimethamine. Combination therapy of chloroquine and primaquine has proven
      ineffective and combinations of sulfadoxine-pyrimethamine with either quinine or
      chloroquine have also shown poor efficacy. Recent studies indicate that
      artemisinin derivatives, such as artesunate, remain highly efficacious in
      treating P. falciparum malaria. Available data suggest that artemisinins,
      quinine, doxycyline, mefloquine-artesunate and azithromycin-artesunate
      combination therapy remain efficacious in the treatment of P. falciparum malaria
      in Bangladesh. 

PMID- 24127211
TI  - Yohanns Bellaiche: Mastering multiscale morphology. Interview by Caitlin Sedwick.

PMID- 24127212
TI  - Nonrandom template segregation: a way to break the symmetry of stem cells.
AB  - Whether DNA segregates in a biased way has been a subject of intense controversy
      and debate. Although highly provocative in its biological implications, if true,
      technical problems have limited researchers from drawing firm conclusions from
      the data. Elabd et al. (2013. J. Cell Biol.
      http://dx.doi.org/10.1083/jcb.201307110/DC1) now show a high frequency of
      nonrandom template segregation during differentiation of embryonic stem cells
      using rigorous experimentation and implicate the methyltransferase Dnmt3 as a key
      regulator of this process. 

PMID- 24127213
TI  - Cell biology in neuroscience: cellular and molecular mechanisms underlying
      presynapse formation.
AB  - Synapse formation is a highly regulated process that requires the coordination of
      many cell biological events. Decades of research have identified a long list of
      molecular components involved in assembling a functioning synapse. Yet how the
      various steps, from transporting synaptic components to adhering synaptic
      partners and assembling the synaptic structure, are regulated and precisely
      executed during development and maintenance is still unclear. With the
      improvement of imaging and molecular tools, recent work in vertebrate and
      invertebrate systems has provided important insight into various aspects of
      presynaptic development, maintenance, and trans-synaptic signals, thereby
      increasing our understanding of how extrinsic organizers and intracellular
      mechanisms contribute to presynapse formation. 

PMID- 24127214
TI  - Nutrient-sensing pathways and metabolic regulation in stem cells.
AB  - Stem cells exert precise regulation to maintain a balance of self-renewal and
      differentiation programs to sustain tissue homeostasis throughout the life of an
      organism. Recent evidence suggests that this regulation is modulated, in part,
      via metabolic changes and modifications of nutrient-sensing pathways such as mTOR
      and AMPK. It is becoming increasingly clear that stem cells inhibit oxidative
      phosphorylation in favor of aerobic glycolysis for energy production. Recent
      progress has detailed the molecular mechanisms of this metabolic phenotype and
      has offered insight into new metabolic pathways that may be involved in stem cell
      homeostasis. 

PMID- 24127215
TI  - DNA methyltransferase-3-dependent nonrandom template segregation in
      differentiating embryonic stem cells.
AB  - Asymmetry of cell fate is one fundamental property of stem cells, in which one
      daughter cell self-renews, whereas the other differentiates. Evidence of
      nonrandom template segregation (NRTS) of chromosomes during asymmetric cell
      divisions in phylogenetically divergent organisms, such as plants, fungi, and
      mammals, has already been shown. However, before this current work, asymmetric
      inheritance of chromatids has never been demonstrated in differentiating
      embryonic stem cells (ESCs), and its molecular mechanism has remained unknown.
      Our results unambiguously demonstrate NRTS in asymmetrically dividing,
      differentiating human and mouse ESCs. Moreover, we show that NRTS is dependent on
      DNA methylation and on Dnmt3 (DNA methyltransferase-3), indicating a molecular
      mechanism that regulates this phenomenon. Furthermore, our data support the
      hypothesis that retention of chromatids with the "old" template DNA preserves the
      epigenetic memory of cell fate, whereas localization of "new" DNA strands and de
      novo DNA methyltransferase to the lineage-destined daughter cell facilitates
      epigenetic adaptation to a new cell fate. 

PMID- 24127216
TI  - The formins Cdc12 and For3 cooperate during contractile ring assembly in
      cytokinesis.
AB  - Both de novo-assembled actin filaments at the division site and existing
      filaments recruited by directional cortical transport contribute to contractile
      ring formation during cytokinesis. However, it is unknown which source is more
      important. Here, we show that fission yeast formin For3 is responsible for node
      condensation into clumps in the absence of formin Cdc12. For3 localization at the
      division site depended on the F-BAR protein Cdc15, and for3 deletion was
      synthetic lethal with mutations that cause defects in contractile ring formation.
      For3 became essential in cells expressing N-terminal truncations of Cdc12, which
      were more active in actin assembly but depended on actin filaments for
      localization to the division site. In tetrad fluorescence microscopy, double
      mutants of for3 deletion and cdc12 truncations were severely defective in
      contractile ring assembly and constriction, although cortical transport of actin
      filaments was normal. Together, these data indicate that different formins
      cooperate in cytokinesis and that de novo actin assembly at the division site is
      predominant for contractile ring formation. 

PMID- 24127217
TI  - Whole-genome screening identifies proteins localized to distinct nuclear bodies.
AB  - The nucleus is a unique organelle that contains essential genetic materials in
      chromosome territories. The interchromatin space is composed of nuclear
      subcompartments, which are defined by several distinctive nuclear bodies believed
      to be factories of DNA or RNA processing and sites of transcriptional and/or
      posttranscriptional regulation. In this paper, we performed a genome-wide
      microscopy-based screening for proteins that form nuclear foci and characterized
      their localizations using markers of known nuclear bodies. In total, we
      identified 325 proteins localized to distinct nuclear bodies, including nucleoli
      (148), promyelocytic leukemia nuclear bodies (38), nuclear speckles (27),
      paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodies (5), Polycomb bodies
      (2), and uncharacterized nuclear bodies (64). Functional validation revealed
      several proteins potentially involved in the assembly of Cajal bodies and
      paraspeckles. Together, these data establish the first atlas of human proteins in
      different nuclear bodies and provide key information for research on nuclear
      bodies. 

PMID- 24127218
TI  - Interdependence of muscle atrophy and bone loss induced by mechanical unloading.
AB  - Mechanical unloading induces muscle atrophy and bone loss; however, the time
      course and interdependence of these effects is not well defined. We subjected 4
      month-old C57BL/6J mice to hindlimb suspension (HLS) for 3 weeks, euthanizing 12
      to 16 mice on day (D) 0, 7, 14, and 21. Lean mass was 7% to 9% lower for HLS
      versus control from D7-21. Absolute mass of the gastrocnemius (gastroc) decreased
      8% by D7, and was maximally decreased 16% by D14 of HLS. mRNA levels of Atrogin-1
      in the gastroc and quadriceps (quad) were increased 99% and 122%, respectively,
      at D7 of HLS. Similar increases in MuRF1 mRNA levels occurred at D7. Both
      atrogenes returned to baseline by D14. Protein synthesis in gastroc and quad was
      reduced 30% from D7-14 of HLS, returning to baseline by D21. HLS decreased
      phosphorylation of SK61, a substrate of mammalian target of rapamycin (mTOR), on
      D7-21, whereas 4E-BP1 was not lower until D21. Cortical thickness of the femur
      and tibia did not decrease until D14 of HLS. Cortical bone of controls did not
      change over time. HLS mice had lower distal femur bone volume fraction (-22%) by
      D14; however, the effects of HLS were eliminated by D21 because of the decline of
      trabecular bone mass of controls. Femur strength was decreased approximately 13%
      by D14 of HLS, with no change in tibia mechanical properties at any time point.
      This investigation reveals that muscle atrophy precedes bone loss during
      unloading and may contribute to subsequent skeletal deficits. Countermeasures
      that preserve muscle may reduce bone loss induced by mechanical unloading or
      prolonged disuse. Trabecular bone loss with age, similar to that which occurs in
      mature astronauts, is superimposed on unloading. Preservation of muscle mass,
      cortical structure, and bone strength during the experiment suggests muscle may
      have a greater effect on cortical than trabecular bone.

PMID- 24127219
TI  - Assessment of the genotoxic and carcinogenic potentials of 3-aminothiophene
      derivatives using in vitro and in silico methodologies.
AB  - Thiophene derivatives, a class of compounds widely used in products such as
      pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern.
      Indeed, the thiophene ring is often considered as a structural moiety that may be
      involved in toxic effects in humans. We primarily focus on the
      genotoxic/mutagenic and carcinogenic potentials of the methyl 3-amino-4
      methylthiophene-2-carboxylate (1), a precursor of the articaine local anesthetic
      (4) which falls within the scope of the European REACH (Registration, Evaluation,
      Authorisation and restriction of CHemicals) legislation. To discern some
      structure-toxicity relationships, we also studied two related compounds, namely
      the 3-amino 4-methylthiophene (2) and the 2-acetyl 4-chlorothiophene (3).
      Techniques employed to assess mutagenic and DNA-damaging effects involved the
      Salmonella mutagenicity assay (or Ames test) and the single-cell gel
      electrophoresis assay (or Comet assay). In the range of tested doses, none of
      these derivatives led to a positive response in the Ames tests and DNA damage was
      only observed in the Comet assay after high concentration exposure of 2. The
      study of their carcinogenic potential using the in vitro SHE (Syrian Hamster
      Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A
      combination of experimental data with in silico predictions of the reactivity of
      thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize
      possible pathways leading to these toxicological profiles.

PMID- 24127220
TI  - Nickel dichalcogenide hollow spheres: controllable fabrication, structural
      modification, and magnetic properties.
AB  - Magnetize your chemistry! A facile hydrothermal synthetic route was developed for
      the synthesis of uniform NiS2 hollow spheres, which could be transformed into
      NiSe2 and NiTe2 hollow spheres through a chemical conversion process.
      Furthermore, NiS and NiO hollow spheres could be selectively obtained by
      calcination of NiS2 hollow spheres at different temperatures. 

PMID- 24127221
TI  - Optimal sequencing of anti-HER2 therapy throughout the continuum of HER2-positive
      breast cancer: evidence and clinical considerations.
AB  - With the advent of the monoclonal antibody trastuzumab over 2 decades ago for
      breast cancer therapy, the outcome of patients with human epidermal growth factor
      receptor (HER) 2-positive disease has improved dramatically. Based on its
      substantial efficacy and good tolerability, trastuzumab has become the
      therapeutic gold standard for early as well as advanced breast cancer.
      Nevertheless, despite adjuvant trastuzumab, patients do experience recurrence and
      require further anti-HER2-targeted therapy. Next to the small molecule tyrosine
      kinase inhibitor lapatinib, which was the first approved therapy option after
      trastuzumab failure, several new anti-HER2 agents are currently already available
      for clinical use [i.e. pertuzumab, T-DM1 (trastuzumab emtansine)] or are still
      being evaluated (e.g. afatinib, neratinib). Recent evidence from neoadjuvant as
      well as metastatic therapy suggests that dual blockade may be superior to single
      agent HER2 blockade. While the number of available or potential therapies has
      increased considerably, no additional predictive biomarkers beyond HER2 have been
      validated for the use of the different anti-HER2 therapies. Moreover, novel
      therapeutic concepts such as the antibody-drug conjugate T-DM1 warrant excellent
      determination methodology for HER2 and suggest re-evaluation of tumor biology
      upon first metastasis. The clinical challenge remains to optimally choose,
      utilize, and sequence anti-HER2 therapy in early as well as metastatic breast
      cancer. This article will provide evidence-based guidance for sequencing anti
      HER2 therapy throughout the continuum of breast cancer therapy. 

PMID- 24127222
TI  - beta-Adrenoceptor modulation in chronic obstructive pulmonary disease: present
      and future perspectives.
AB  - The common coexistence of chronic obstructive pulmonary disease (COPD) and
      cardiovascular disease (CVD) presents several therapeutic constraints that have
      not been comprehensively investigated. Pharmacologic modulation of beta
      adrenoceptor (beta-AR) function is one of the critical issues in the treatment of
      these patients because inhaled beta(2)-AR agonists may induce adverse events in
      patients with COPD, mainly in those with coexisting CVD. Moreover, the use of
      beta-AR blockers has traditionally been contraindicated in COPD, mainly because
      of the potential for acute bronchospasm and increased airway hyperresponsiveness
      after their administration. However, there now appears to be good evidence that
      beta-AR blockers are not only safe but may have benefits in COPD that extend
      beyond a reduction in cardiovascular mortality. This article starts with a
      succinct outline of the evolution in our understanding of beta-AR modulation in
      COPD, touching on treatment of COPD with beta-AR agonists and the issues of beta
      AR blockade and cardioselectivity in patients with comorbid CVD. We then
      summarize the current evidence for a COPD benefit from beta-AR blockers and
      hypothesize on the mode of action. Finally, we provide a view of the future
      landscape in terms of therapeutic possibilities and what still needs to be
      resolved, based on our opinion.

PMID- 24127223
TI  - Enzalutamide: a review of its use in metastatic, castration-resistant prostate
      cancer.
AB  - Enzalutamide (MDV3100, XTANDI((r))) is an androgen receptor inhibitor that is
      indicated for the treatment of metastatic, castration-resistant, prostate cancer
      (mCRPC) that has progressed despite treatment with docetaxel. This article
      reviews the pharmacology, efficacy and tolerability of enzalutamide relevant to
      this indication. In a randomized, double-blind, placebo-controlled,
      multinational, phase III trial in patients with mCRPC progressing after docetaxel
      therapy, enzalutamide significantly prolonged overall survival (OS), delayed
      prostate specific antigen progression and prolonged radiographic progression-free
      survival and time to the first skeletal event. The median OS was 18.4 months in
      the enzalutamide group and 13.6 months in the placebo group, which represents a
      37 % reduction in the mortality risk in the enzalutamide group. Enzalutamide was
      also associated with significant benefits in health-related quality of life and
      in pain palliation. Enzalutamide was generally as well tolerated as placebo
      during the trial, with most adverse events at a mild or moderate level of
      severity. Enzalutamide carries a small increased risk of seizures that appears to
      be dose-dependent. Enzalutamide is an efficacious and well tolerated treatment
      for this severe, rapidly progressive disease.

PMID- 24127224
TI  - Liquid coordination complexes formed by the heterolytic cleavage of metal
      halides.

PMID- 24127226
TI  - Role of magnetic resonance diffusion-weighted imaging in differentiating lacrimal
      masses.
AB  - PURPOSE: To evaluate the role of magnetic resonance (MR) diffusion-weighted
      imaging (DWI) in discriminating lacrimal masses, including neoplastic and
      nonneoplastic entities. MATERIALS AND METHODS: Forty-four patients with lacrimal
      masses underwent conventional MRI and DWI. The apparent diffusion coefficient
      (ADC) values of each mass and the ipsilateral temporal lobe were measured and the
      ratios of the lesion to temporal lobe ADC were calculated. RESULTS: Pleomorphic
      adenomas had significantly higher ADC values (1.37 +/- 0.22 * 10(-3) mm(2) /sec)
      and ADC ratios (1.85 +/- 0.34) than malignant tumors (1.03 +/- 0.19 * 10(-3)
      mm(2) /sec, 1.37 +/- 0.27) (P < 0.001), inflammatory pseudotumors (0.9 +/- 0.08 *
      10(-3) mm(2) /sec, 1.19 +/- 0.07) (P < 0.01), reactive lymphoid hyperplasias
      (RLHs) (0.6 +/- 0.06 * 10(-3) mm(2) /sec, 0.79 +/- 0.07) (P < 0.001), and
      lymphomas (0.55 +/- 0.06 * 10(-3) mm(2) /sec, 0.74 +/- 0.08) (P < 0.001). RLHs
      and lymphomas had significantly lower ADC values and ADC ratios than malignant
      tumors (P < 0.05) and inflammatory pseudotumors (P < 0.05). An ADC value of less
      than 1.14 * 10(-3) mm(2) /sec and an ADC ratio of less than 1.6 were optimal for
      differentiating malignant tumors from benign tumors (sensitivity: 80 and 90%,
      specificity: 100 and 88.9%, respectively). An ADC value of less than 0.76 * 10(
      3) mm(2) /sec and an ADC ratio of less than 1.0 were optimal for distinguishing
      lymphoproliferative disorders from inflammatory pseudotumors (sensitivity: 100%,
      specificity: 100% for both). CONCLUSION: DWI can help differentiate lacrimal
      masses and provides a potential clinical tool for noninvasive tissue
      characterization.

PMID- 24127228
TI  - Tumor volumetry as a prognostic factor in the management of T4a laryngeal cancer.
AB  - OBJECTIVES/HYPOTHESIS: The role of tumor volume in T4a laryngeal cancer remains
      unclear among different treatment modalities. Using tumor volumetry, we
      investigated the impact of primary tumor volume on this subset of patients. STUDY
      DESIGN: Retrospective cohort study of 62 T4a laryngeal cancer patients. METHODS:
      From October 2002 to September 2010, 48 patients were treated with definitive
      chemoradiation therapy (CRT), and 14 patients had undergone total laryngectomy.
      Tumor volume was calculated and was correlated with the overall survival (OS),
      progression-free survival (PFS), and local control rate (LCR) data of each
      treatment group. RESULTS: The 5-year OS, PFS, and LCR were significantly lower in
      the CRT group with tumor volume >= 15 cm(3) (22.5% vs. 48.7%, P = 0.009; 32.2%
      vs. 64.3%, P = 0.003; 45.2% vs. 67.3%, P = 0.039). Multivariate analysis showed
      that tumor volume was an independent poor prognosticator for OS, PFS, and LCR in
      the CRT group. For tumor volume >= 15 cm(3) , total laryngectomy provided a
      significantly higher 5-year OS and PFS (54.5% vs. 22.5%, P = 0.039; 80.0% vs.
      32.2%, P = 0.017) than for those tumors treated with definitive CRT. CONCLUSIONS:
      Patients with T4a laryngeal cancer with primary tumor volume >= 15 cm(3) had
      poorer survival outcomes after definitive CRT compared with total laryngectomy.
      It was also an independent poor prognosticator on LCR, PFS, and OS for those
      receiving definitive CRT. For patients with tumor volume >= 15 cm(3), total
      laryngectomy provided a better survival outcome than definitive CRT.

PMID- 24127225
TI  - Identification of novel candidate gene loci and increased sex chromosome
      aneuploidy among infants with conotruncal heart defects.
AB  - Congenital heart defects (CHDs) are common malformations, affecting four to eight
      per 1,000 total births. Conotruncal defects are an important pathogenetic subset
      of CHDs, comprising nearly 20% of the total. Although both environmental and
      genetic factors are known to contribute to the occurrence of conotruncal defects,
      the causes remain unknown for most. To identify novel candidate genes/loci, we
      used array comparative genomic hybridization to detect chromosomal
      microdeletions/duplications. From a population base of 974,579 total births born
      during 1999-2004, we screened 389 California infants born with tetralogy of
      Fallot or d-transposition of the great arteries. We found that 1.7% (5/288) of
      males with a conotruncal defect had sex chromosome aneuploidy, a sevenfold
      increased frequency (relative risk = 7.0; 95% confidence interval 2.9-16.9). We
      identified eight chromosomal microdeletions/duplications for conotruncal defects.
      From these duplications and deletions, we found five high priority candidate
      genes (GATA4, CRKL, BMPR1A, SNAI2, and ZFHX4). This is the initial report that
      sex chromosome aneuploidy is associated with conotruncal defects among boys.
      These chromosomal microduplications/deletions provide evidence that GATA4, SNAI2,
      and CRKL are highly dosage sensitive genes involved in outflow tract development.
      Genome wide screening for copy number variation can be productive for identifying
      novel genes/loci contributing to non-syndromic common malformations.

PMID- 24127229
TI  - Morphological development of testes in ostrich (Struthio camelus) embryo.
AB  - Although the histological structure of ostrich testis has been studied, very
      little information is currently available on the embryonic development of this
      organ. The aim of this study was to determine the sequence of the histological
      changes in diverse components of the testis in ostrich embryo from embryonic day
      (E) 20 to E42. The main findings were categorized into four histological
      features, i.e., development of sex cords, interstitial tissue and rete ducts, and
      the appearance of defective septa. While the lumen of sex cords, tunica
      albuginea, capsular rete ducts and Leydig cell precursors appeared at E26, the
      filum-shaped defective septa were visible at E36. The emersion of the lumen in
      the primary sex cords and formation of capsular rete ducts in the ostrich embryo
      is considerably different from that in other birds. However, tunica albuginea and
      Leydig cell precursors appeared in a similar pattern to those of other birds. An
      interesting observation was that the primordial germ cell (PGC)-like cells were
      completely distinct, while the capsular rete ducts were formed by trapping of
      some Sertoli cell aggregations in the tunica albuginea. This suggests that
      similar to the primary sex cords, the capsular rete ducts may originate from the
      Sertoli cell aggregations which had corralled some PGCs. Stereological
      estimations in the ostrich embryo testis showed the major proportion of testis is
      occupied by the seminiferous tubules, which is unlike the fowl embryo testis. 

PMID- 24127232
TI  - Structures of class B G protein-coupled receptors: prospects for drug discovery.
AB  - New members in the GPCR photo gallery! Crystal structures of class B G protein
      coupled receptors, which bind peptide hormones, have been solved [see picture of
      the corticotropin-releasing factor receptor 1 (blue) and a bound allosteric
      nonpeptide antagonist (green)]. The structures provide a basis for a rational
      design of better drugs for diabetes, osteoporosis, migraine, or depression. 

PMID- 24127231
TI  - Rapid determination of quetiapine in blood by gas chromatography-mass
      spectrometry. Application to post-mortem cases.
AB  - A simple, fast and sensitive method for the determination of quetiapine in human
      blood has been developed and validated. The method involved a basic liquid-liquid
      extraction procedure and subsequent analysis by gas chromatography-mass
      spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro
      acetamide and chorotrimethylsilane (99 : 1). The methods of validation included
      linearity with a correlation coefficient > 0.99 over the range 0.02-1 ug ml(-1),
      intra- and interday precision (always < 12%) and accuracy (mean relative error
      always < 12%) to meet the bioanalytical acceptance criteria. The limit of
      detection was 0.005 ug ml(-1). The procedure was further applied to post mortems
      from the Institute of Legal Medicine, University of Santiago de Compostela.

PMID- 24127230
TI  - Injectable foams for regenerative medicine.
AB  - The design of injectable biomaterials has attracted considerable attention in
      recent years. Many injectable biomaterials, such as hydrogels and calcium
      phosphate cements (CPCs), have nanoscale pores that limit the rate of cellular
      migration and proliferation. While introduction of macroporosity has been
      suggested to increase cellular infiltration and tissue healing, many conventional
      methods for generating macropores often require harsh processing conditions that
      preclude their use in injectable foams. In recent years, processes such as
      porogen leaching, gas foaming, and emulsion-templating have been adapted to
      generate macroporosity in injectable CPCs, hydrogels, and hydrophobic polymers.
      While some of the more mature injectable foam technologies have been evaluated in
      clinical trials, there are challenges remaining to be addressed, such as the
      biocompatibility and ultimate fate of the sacrificial phase used to generate
      pores within the foam after it sets in situ. Furthermore, while implantable
      scaffolds can be washed extensively to remove undesirable impurities, all of the
      components required to synthesize injectable foams must be injected into the
      defect. Thus, every compound in the foam must be biocompatible and noncytotoxic
      at the concentrations utilized. As future research addresses these critical
      challenges, injectable macroporous foams are anticipated to have an increasingly
      significant impact on improving patient outcomes for a number of clinical
      procedures.

PMID- 24127233
TI  - Myofilament protein carbonylation contributes to the contractile dysfunction in
      the infarcted LV region of mouse hearts.
AB  - AIMS: The region-specific mechanical function of left ventricular (LV) murine
      cardiomyocytes and the role of phosphorylation and oxidative modifications of
      myofilament proteins were investigated in the process of post-myocardial
      infarction (MI) remodelling 10 weeks after ligation of the left anterior
      descending (LAD) coronary artery. METHODS AND RESULTS: Permeabilized murine
      cardiomyocytes from the remaining anterior and a remote non-infarcted inferior LV
      area were compared with those of non-infarcted age-matched controls. Myofilament
      phosphorylation, sulfhydryl (SH) oxidation, and carbonylation were also assayed.
      Ca(2+) sensitivity of force production was significantly lower in the anterior
      wall (pCa50: 5.81 +/- 0.03, means +/- SEM, at 2.3 um sarcomere length) than that
      in the controls (pCa50: 5.91 +/- 0.02) or in the MI inferior area (pCa50: 5.88 +/
      0.02). The level of troponin I phosphorylation was lower and that of myofilament
      protein SH oxidation was higher in the anterior location relative to controls,
      but these changes did not explain the differences in Ca(2+) sensitivities. On the
      other hand, significantly higher carbonylation levels, [e.g. in myosin heavy
      chain (MHC) and actin] were observed in the MI anterior wall [carbonylation index
      (CI), CIMHC: 2.06 +/- 0.46, CIactin: 1.46 +/- 0.18] than in the controls (CI: 1).
      In vitro Fenton-based myofilament carbonylation in the control cardiomyocytes
      also decreased the Ca(2+) sensitivity of force production irrespective of the
      phosphorylation status of the myofilaments. Furthermore, the Ca(2+) sensitivity
      correlated strongly with myofilament carbonylation levels in all investigated
      samples. CONCLUSION: Post-MI myocardial remodelling involves increased
      myofibrillar protein carbonylation and decreased Ca(2+) sensitivity of force
      production, leading potentially to contractile dysfunction in the remaining
      cardiomyocytes of the infarcted area.

PMID- 24127234
TI  - What is fibromyalgia, how is it diagnosed, and what does it really mean?

PMID- 24127235
TI  - Morphofunctional changes of female germinal epithelium to support spermatozoa
      along the annual reproductive cycle in an inseminating catfish (Trachelyopterus
      galeatus, Auchenipteridae).
AB  - The reproductive system of some fish species presents elaborate mechanisms by
      which the females store spermatozoa inside their ovaries, keeping them viable for
      fertilization for an extended period of time. However, as intriguing as this
      sperm storage is, it is not yet understood how the sperm can remain viable in the
      ovary. Aiming to understand this phenomenon, the epithelium covering the ovarian
      lamellae, that is, the germinal epithelium, of the Cangati (Trachelyopterus
      galeatus), an inseminating catfish, was evaluated taking into account the
      different stages of the annual reproductive cycle. The germinal epithelium
      morphology changed during the annual reproductive cycle, presumably in
      preparation to receive the spermatozoa and keep them viable until fertilization.
      There was a progressive increase of the epithelium height. Also the number of
      intercellular junctions, desmosomes, and extended tight junctions, apparently
      increased forming chains that could be regarded as a barrier to isolate the sperm
      from the female immune system. Synthetic organelles were active releasing
      cytoplasmic granules and secretion in the epithelial enfolds in which the
      spermatozoa were deeply embedded. Concomitantly, oogonium nests were formed in
      the germinal epithelium during early folliculogenesis.

PMID- 24127236
TI  - Interaction of allergy history and antibodies to specific varicella-zoster virus
      proteins on glioma risk.
AB  - Glioma is the most common cancer of the central nervous system but with few
      confirmed risk factors. It has been inversely associated with chicken pox,
      shingles and seroreactivity to varicella virus (VZV), as well as to allergies and
      allergy-associated IgE. The role of antibody reactivity against individual VZV
      antigens has not been assessed. Ten VZV-related proteins, selected for high
      immunogenicity or known function, were synthesized and used as targets for
      antibody measurements in the sera of 143 glioma cases and 131 healthy controls
      selected from the San Francisco Bay Area Adult Glioma Study. Glioma cases
      exhibited significantly reduced seroreactivity compared to controls for six
      antigens, including proteins IE63 [odds ratio (OR) = 0.26, 95% confidence
      interval (CI): 0.12-0.58, comparing lowest quartile to highest) and the VZV
      unique protein ORF2p (OR = 0.44, 95% CI: 0.21-0.96, lowest quartile to highest).
      When stratifying the study population into those with low and high self-reported
      allergy history, VZV protein seroreactivity was only associated inversely with
      glioma among individuals self-reporting more than two allergies. The data provide
      insight into both allergy and VZV effects on glioma: strong anti-VZV reactions in
      highly allergic individuals are associated with reduced occurrence of glioma.
      This result suggests a role for specificity in the anti-VZV immunity in brain
      tumor suppression for both individual VZV antigens and in the fine-tuning of the
      immune response by allergy. Anti-VZV reactions may also be a biomarker of
      effective CNS immunosurveillance owing to the tropism of the virus. 

PMID- 24127238
TI  - Ethical issues in HIV prevention research with people who inject drugs.
AB  - BACKGROUND: Injection drug use continues to significantly contribute to new
      infections with HIV. Moreover, conducting HIV prevention research with people who
      inject drugs (PWIDs) can be complicated for an array of practical, social, legal,
      and ethical reasons. It is critical that these research efforts are sensitive to
      the particular vulnerabilities associated with injection drug use as well as
      those related to being at risk of acquiring HIV so as to minimize harm to
      participants in research. PURPOSE: To describe how we addressed some of these
      ethical challenges during the course of a large-scale multinational randomized
      HIV prevention trial involving PWIDs, which was successfully completed. METHODS:
      The ethical issues encountered during the life cycle of the trial were cataloged
      by the principal investigator, study coordinator, and ethicist working on the
      trial. Relevant study documents were then reviewed to provide pertinent details.
      The ethical issues unique to the trial were then described. RESULTS: Before
      implementation, the trial faced particularly complex challenges related to the
      vulnerability of PWIDs, where HIV seroincidence rates in the population were high
      and legal policies and stigma regarding injection drug use was severe.
      Accordingly, a rapid policy assessment was commissioned, and a series of
      community engagement activities were conducted. During the trial, in addition to
      using careful standard operating procedures regarding all aspects of trial
      conduct and extensive staff training, the trial standardized informed consent
      procedures and assessed them. Furthermore, social harms were monitored along with
      physical harms and adverse events. Following the decision to close the study, it
      was critical to develop an orderly and safe process for closing it. The issue of
      post-trial access to the study medication and a complex intervention also
      surfaced for consideration. LIMITATIONS: The issues described in this article are
      necessarily limited to how they manifested themselves within the context of a
      particular trial that was conducted in two countries. In addition, other
      stakeholders may have divergent views on the ethical issues described and may
      also have identified additional ethical issues that would warrant examination.
      CONCLUSIONS: Adopting similar approaches to addressing ethical issues in future
      research promises to facilitate this work so that needed strategies to prevent
      HIV infection among PWIDs can be safely and appropriately tested. Future trials
      enrolling PWIDs who are at risk of detainment should identify ways of mapping
      closely their experiences and perceptions in order to better apprehend some of
      the ethical issues at stake. In addition, scholarly and policy work needs to
      address the ethical issues related to post-trial access to multi-modal
      interventions that may be desired by participants, but are not shown to be
      effective in achieving the primary outcomes of the study.

PMID- 24127237
TI  - Deficiency of Sef is associated with increased postnatal cortical bone mass by
      regulating Runx2 activity.
AB  - Sef (similar expression to fgf genes) is a feedback inhibitor of fibroblast
      growth factor (FGF) signaling and functions in part by binding to FGF receptors
      and inhibiting their activation. Genetic studies in mice and humans indicate an
      important role for fibroblast growth factor signaling in bone growth and
      homeostasis. We, therefore, investigated whether Sef had a function role in
      skeletal acquisition and remodeling. Sef expression is increased during
      osteoblast differentiation in vitro, and LacZ staining of Sef+/- mice showed high
      expression of Sef in the periosteum and chondro-osseous junction of neonatal and
      adult mice. Mice with a global deletion of Sef showed increased cortical bone
      thickness, bone volume, and increased periosteal perimeter by micro-computed
      tomography (micro-CT). Histomorphometric analysis of cortical bone revealed a
      significant increase in osteoblast number. Interestingly, Sef-/- mice showed very
      little difference in trabecular bone by micro-CT and histomorphometry compared
      with wild-type mice. Bone marrow cells from Sef-/- mice grown in osteogenic
      medium showed increased proliferation and increased osteoblast differentiation
      compared with wild-type bone marrow cells. Bone marrow cells from Sef-/- mice
      showed enhanced FGF2-induced activation of the ERK pathway, whereas bone marrow
      cells from Sef transgenic mice showed decreased FGF2-induced signaling. FGF2
      induced acetylation and stability of Runx2 was enhanced in Sef-/- bone marrow
      cells, whereas overexpression of Sef inhibited Runx2-responsive luciferase
      reporter activity. Bone marrow from Sef-/- mice showed enhanced hematopoietic
      lineage-dependent and osteoblast-dependent osteoclastogenesis and increased bone
      resorptive activity relative to wild-type controls in in vitro assays, whereas
      overexpression of Sef inhibited osteoclast differentiation. Taken together, these
      studies indicate that Sef has specific roles in osteoblast and osteoclast
      lineages and that its absence results in increased osteoblast and osteoclast
      activity with a net increase in cortical bone mass.

PMID- 24127240
TI  - Quantitative analysis of five tobacco-specific N-nitrosamines in urine by liquid
      chromatography-atmospheric pressure ionization tandem mass spectrometry.
AB  - A liquid chromatography tandem mass spectrometry (LC/MS/MS) method was developed
      and validated for the determination of five total tobacco-specific N-nitrosamines
      (TSNA), including free and conjugated forms in urine. The limits of detection for
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N'-nitrosonornicotine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, N'-nitrosoanatabine and N'
      nitrosoanabasine were 0.6, 0.6, 10.0, 0.4 and 0.4 pg/mL, respectively, with a
      linear calibration range of up to 20,000 pg/mL. Intra- and inter-day precision
      for TSNA measurements ranged from 0.82 to 3.67% and from 2.04 to 7.73%
      respectively. For total TSNAs, the beta-glucuronidase amount was optimized for
      hydrolysis time and yield. Different liquid chromatography columns and mobile
      phases with different pH conditions were evaluated. The validated method was then
      applied to 50 smoker and 30 nonsmoker urine samples. Our results suggest that
      this sensitive and relatively simple analytical method is suitable for
      application to epidemiological investigations of health risks associated with the
      exposure to tobacco smoke or secondhand smoke in both smokers and nonsmokers.

PMID- 24127241
TI  - An actinide Zintl cluster: a tris(triamidouranium)MU3-eta2:eta2:eta2
      heptaphosphanortricyclane and its diverse synthetic utility.

PMID- 24127239
TI  - Assessing patient preferences for treatment options and process of care in
      inflammatory bowel disease: a critical review of quantitative data.
AB  - Inflammatory bowel disease (IBD), consisting of both Crohn's disease (CD) and
      ulcerative colitis (UC), are chronic inflammatory conditions of the intestinal
      tract. As there is no cure for either CD or UC, patients with these conditions
      face numerous treatment decisions regarding their disease. The aim of this review
      is to evaluate literature regarding quantitative studies of patient preferences
      in therapy for IBD with a focus on the emerging technique of stated preference
      and its application in IBD. Numerous simple survey-based studies have been
      performed evaluating IBD patients' preferences for medication frequency, mode of
      delivery, potential adverse events, etc., as well as variations in these
      preferences. These studies are limited, however, as they are purely descriptive
      in nature with limited quantitative information on the relative value of
      treatment alternatives. Time trade-off and standard-gamble studies have also been
      utilized to quantify patient utility for various treatment options or outcomes.
      However, these types of studies suffer from inaccurate assumptions regarding
      patient choice behavior. Stated preference is an emerging robust methodology
      increasingly utilized in health care that can determine the relative utility for
      a therapy option as well as its specific attributes (such as efficacy or adverse
      side effects). Stated preference techniques have begun to be applied in IBD and
      offer an innovative way of examining the numerous therapy options these patients
      and their providers face. 

PMID- 24127242
TI  - Refill adherence and self-reported adverse drug reactions and sub-therapeutic
      effects: a population-based study.
AB  - PURPOSE: To assess refill adherence to dispensed oral long-term medications among
      the adult population and to investigate whether the percentages of self-reported
      adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for
      medications with adequate refill adherence, oversupply, and undersupply. METHOD:
      Survey responses on self-reported ADRs and STEs were linked to the Swedish
      Prescribed Drug Register in a cross-sectional population-based study. Refill
      adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications
      was measured using the continuous measure of medication acquisition (CMA). The
      percentages of self-reported ADRs and STEs were compared between medications with
      adequate refill adherence (CMA 0.8-1.2), oversupply (CMA > 1.2), and undersupply
      (CMA < 0.8). RESULTS: The study included 1827 persons, and the refill adherence
      was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti
      diabetic medications. Overall, 65.7% of the medications had adequate refill
      adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self
      reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs
      and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs. CONCLUSIONS: Adequate refill
      adherence was found in two thirds of the medication therapies. ADRs and STEs were
      unexpectedly equally commonly reported for medications with adequate refill
      adherence, oversupply, and undersupply. These results suggest that a better
      understanding of patients' refill behaviors and their perceived medication
      adverse outcomes is needed and should be considered in improving medication
      management. The impact of individual and healthcare factors that may influence
      the association between refill adherence and reported medication adverse outcomes
      should be investigated in future studies.

PMID- 24127243
TI  - Association of knee confidence with pain, knee instability, muscle strength, and
      dynamic varus-valgus joint motion in knee osteoarthritis.
AB  - OBJECTIVE: To investigate associations between self-reported knee confidence and
      pain, self-reported knee instability, muscle strength, and dynamic varus-valgus
      joint motion during walking. METHODS: We performed a cross-sectional analysis of
      baseline data from 100 participants with symptomatic and radiographic medial
      tibiofemoral compartment osteoarthritis (OA) and varus malalignment recruited for
      a randomized controlled trial. The extent of knee confidence, assessed using a 5
      point Likert scale item from the Knee Injury and Osteoarthritis Outcome Score,
      was set as the dependent variable in univariable and multivariable ordinal
      regression, with pain during walking, self-reported knee instability, quadriceps
      strength, and dynamic varus-valgus joint motion during walking as independent
      variables. RESULTS: One percent of the participants were not troubled with lack
      of knee confidence, 17% were mildly troubled, 50% were moderately troubled, 26%
      were severely troubled, and 6% were extremely troubled. Significant associations
      were found between worse knee confidence and higher pain intensity, worse self
      reported knee instability, lower quadriceps strength, and greater dynamic varus
      valgus joint motion. The multivariable model consisting of the same variables
      significantly accounted for 24% of the variance in knee confidence (P < 0.001).
      CONCLUSION: Worse knee confidence is associated with higher pain, worse self
      reported knee instability, lower quadriceps muscle strength, and greater dynamic
      varus-valgus joint motion during walking. Since previous research has shown that
      worse knee confidence is predictive of functional decline in knee OA, addressing
      lack of knee confidence by treating these modifiable impairments could represent
      a new therapeutic target.

PMID- 24127244
TI  - Seasonal lectin binding variations of thumb pad in the frog (Pelophylax
      ridibundus).
AB  - The thumb pad is one of the most common secondary sexual characteristics in
      frogs. Although it is known that amphibian skin has affinity for several lectins,
      there is no report regarding lectin-binding affinity of the thumb pad or its
      structural components. This study investigated localization and seasonal
      variation of specific carbohydrate moieties of glycoconjugates in both the
      epidermal and dermal components of the frog thumb pad at the light microscopic
      level using lectin histochemistry. The study consisted of four seasonal groups of
      the frog species, Pelophylax ridibundus (Synonym of Rana ridibunda): active,
      prehibernating, hibernating and posthibernating. Four horseradish peroxidase
      conjugated lectins were employed. It was found that dolichos biflorus agglutinin
      (DBA), wheat germ agglutinin (WGA), and ulex europaeus (UEAI) gave positive
      reactions in both epidermal layers and breeding glands. These three lectins bound
      specific secretory cells in the breeding glands, and the distribution of the
      cells and epithelial lectin reactions exhibited seasonal changes. In addition,
      UEA-I and peanut agglutinin (PNA) showed an affinity in granular glands and the
      granular zone of mixed glands. Generally, epidermal lectin binding showed dense
      affinity during the posthibernation period. DBA, UEA-I, and WGA-specific cells in
      the mucous gland decreased gradually until the posthibernation period. These
      findings suggest that differences of lectin binding in the thumb pad may be
      related to functional activities and, thus, seasonal adaptations. Moreover, the
      presence of specific lectin-binding cells in the breeding glands indicated that
      they consisted of heterogeneous secretory cell composition or that the cells were
      at different secretory stages.

PMID- 24127245
TI  - 1961: from there to here: The Journal of Clinical Pharmacology and a new editor.

PMID- 24127246
TI  - Microtubules and actin crosstalk in cell migration and division.
AB  - Crosstalk between the actin cytoskeleton and microtubules promotes symmetry break
      to polarize cells for division, shape changes, and migration. These cellular
      events are crucial for forming tissues, and drive the metastasis of cancer cells.
      Rho GTPases mediate the formation of different types of F-actin that confer
      changes in cortical tension and contraction, and can be regulated by
      microtubules. For example, central spindle microtubules of the mitotic spindle
      stimulate RhoA activity to form long, unbranched F-actin that is crosslinked by
      nonmuscle myosin to form the contractile ring in the equatorial plane of the
      cell. There is greater cortical tension in this area of the cell in comparison to
      the poles, where the formation of short, branched F-actin is favored. In
      migrating cells, growing microtubules that reach into the leading edge promote
      Rac activation and the formation of short, branched F-actin for lamellipodia
      formation. A common theme that is emerging in many fields is that feedback can
      also occur from the cortex to alter microtubule stability. In this manner, cells
      can dynamically respond to intrinsic or extrinsic cues to ensure that their
      division plane is always coupled with the segregation of DNA and cell fate
      determinants, or that they migrate properly to form a tissue.

PMID- 24127247
TI  - A lithium-rich compound Li7Mn(BO3)3 containing Mn2+ in tetrahedral coordination:
      a cathode candidate for lithium-ion batteries.

PMID- 24127248
TI  - The impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy on
      survival in patients with a history of breast cancer--a population-based data
      linkage study.
AB  - Prophylactic surgery including hysterectomy and bilateral salpingo-oophorectomy
      (BSO) is recommended in breast cancer susceptibility gene (BRCA)-positive women,
      whereas in women from the general population, hysterectomy plus BSO may increase
      the risk of overall mortality. The effect of hysterectomy plus BSO on women
      previously diagnosed with breast cancer is unknown. We used data from a
      population-base data linkage study of all women diagnosed with primary breast
      cancer in Queensland, Australia between 1997 and 2008 (n = 21,067). We fitted
      flexible parametric breast cancer-specific and overall survival models with 95%
      confidence intervals (also known as Royston-Parmar models) to assess the impact
      of risk-reducing surgery (removal of uterus, one or both ovaries). We also
      stratified analyses by age 20-49 and 50-79 years, respectively. Overall, 1,426
      women (7%) underwent risk-reducing surgery (13% of premenopausal women and 3% of
      postmenopausal women). No women who had risk-reducing surgery compared to 171 who
      did not have risk-reducing surgery developed a gynaecological cancer. Overall,
      3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy
      plus BSO was associated with significantly reduced risk of death overall
      [adjusted hazard ration (HR), 0.69; 95% confidence interval (CI), 0.53-0.89; p =
      0.005]. Risk reduction was greater among premenopausal women, whose risk of death
      halved (HR, 0.45; 95% CI, 0.25-0.79; p < 0.006). This was largely driven by
      reduction in breast cancer-specific mortality (HR, 0.43; 95% CI, 0.24-0.79; p <
      0.006). This population-based study found that risk-reducing surgery halved the
      mortality risk for premenopausal breast cancer patients. Replication of our
      results in independent cohorts and subsequently randomised trials are needed to
      confirm these findings. 

PMID- 24127249
TI  - Feasibility, acceptability and findings from a pilot randomized controlled
      intervention study on the impact of a book designed to inform patients about
      cancer clinical trials.
AB  - This study was conducted to assess the feasibility, acceptability, and changes in
      knowledge among cancer patients assigned to receive a 160-page book on
      experimental cancer therapies and clinical trials. We enrolled 20 patients with
      cancer who had never participated in a clinical trial and randomly assigned them
      to receive the book either during week 1 or week 4 of the study. We collected
      baseline patient demographic and cancer-related information as well as knowledge
      about cancer clinical trials at week 0. Follow-up surveys were administered at
      weeks 3 and 6 for both study groups. Comparisons were made within and between
      groups randomized to receive the book early (at week 1) to those who received it
      later (at week 4). One hundred percent of data were captured in both groups at
      baseline, which decreased to 77.8% by week 6. The vast majority of participants
      found the book moderately or very useful (89% in the Early Group at week 3 and
      95.5% in the Late Group at week 6). Within group pairwise comparisons found
      significant difference between baseline and week 6 in content-specific knowledge
      scores among participants in the Late Group [79% versus 92.1%, p = 0.01). Global
      knowledge scores increased significantly for variables reflecting knowledge that
      promotes decisions to participate in clinical trials. Providing published reading
      material to patients with cancer is both feasible and acceptable. Offering
      information to patients about cancer clinical trials, using a book designed for
      patients with cancer may influence knowledge related to decision to participate
      in clinical trials.

PMID- 24127250
TI  - Sleepless in Seattle... The International Cancer Education Conference.

PMID- 24127251
TI  - Anion sensing by solution- and surface-assembled osmium(II) bipyridyl rotaxanes.
AB  - We report the preparation of [2]rotaxanes containing an electrochemically and
      optically active osmium(II) bipyridyl macrocyclic component mechanically bonded
      with cationic pyridinium axles. Such interlocked host systems are demonstrated to
      recognise and sense anionic guest species as shown by (1)H NMR, luminescence and
      electrochemical studies. The rotaxanes can be surface assembled on to gold
      electrodes through anion templation under click copper(I)-catalysed Huisgen
      cycloaddition conditions to form rotaxane molecular films, which, after template
      removal, respond electrochemically and selectively to chloride.

PMID- 24127252
TI  - Function-based assessment of structural similarity measurements using metal co
      factor orientation.
AB  - Structure comparison is widely used to quantify protein relationships. Although
      there are several approaches to calculate structural similarity, specifying
      significance thresholds for similarity metrics is difficult due to the inherent
      likeness of common secondary structure elements. In this study, metal co-factor
      location is used to assess the biological relevance of structural alignments. The
      distance between the centroids of bound co-factors adds a chemical and function
      relevant constraint to the structural superimposition of two proteins. This
      additional dimension can be used to define cut-off values for discriminating
      valid and spurious alignments in large alignment sets. The hypothesis underlying
      our approach is that metal coordination sites constrain structural evolution,
      thus revealing functional relationships between distantly related proteins. A
      comparison of three related nitrogenases shows the sequence and fold constraints
      imposed on the protein structures up to 18 A away from the centers of their bound
      metal clusters.

PMID- 24127255
TI  - Unusual labial glands in snakes of the genus Geophis Wagler, 1830 (Serpentes:
      Dipsadinae).
AB  - Geophis belongs to the goo-eating dipsadine assemblage of snakes that are known
      to feed exclusively on earthworms, snails, and slugs. Although the unusual
      feeding strategies of the goo-eating dipsadines are well known (but poorly
      documented), little attention has been paid to their internal anatomy. Here, we
      describe a new and noteworthy morphological and histochemical condition of the
      infralabial glands in three species of Geophis (G. brachycephalus, G. nasalis and
      G. semidoliatus), all earthworm feeders. Their infralabial glands are constituted
      of two distinct parts: an anterolateral portion composed of mucous and seromucous
      cells that stretches from the tip of the dentary to the corner of the mouth, and
      a tubular posteromedial portion that is exclusively seromucous. The anterolateral
      portion receives fibers of the levator anguli oris muscle that attaches on its
      posterodorsal extremity while the posteromedial portion extends posteriorly to
      the corner of the mouth where it receives fibers of the adductor mandibulae
      externus medialis muscle. Furthermore, the posteromedial portion of the
      infralabial gland is constituted by large acini filled with secretion that is
      periodic acid-Schiff positive. These acini release their secretion directly into
      a large lumen located in the middle of the glandular portion. In the three
      species examined, the supralabial glands show a traditional configuration, being
      constituted of mucous and seromucous cells and retaining an enlarged part in its
      caudal region that resembles a Duvernoy's gland. The presence in Geophis of an
      expanded lumen in part of the infralabial gland that is compressed by an adjacent
      muscle suggests a more specialized role for the secretion produced by these
      glands that may not be related to envenomation but rather to prey transport and
      mucus control.

PMID- 24127254
TI  - Structure-guided RP-HPLC chromatography of diastereomeric alpha-helical peptide
      analogs substituted with single amino acid stereoisomers.
AB  - An alpha-helical model peptide (Ac-EAEKAAKE-X-EKAAKEAEK-amide) was used as a
      template to examine the efficacy of conventional reversed-phase high-performance
      liquid chromatography (RP-HPLC) in separating peptide analogs with single
      substitutions (at position X) of diasteromeric amino acids Ile, allo-Ile, d-Ile
      and d-allo-Ile. We compared differences in peptide retention behavior on a C8
      column and a C18 column at different temperatures. We demonstrated how subtle
      differences in peptide secondary structure affected by the different
      substitutions of amino acids with identical overall hydrophobicity enabled
      effective resolution of these peptide analogs. We also demonstrated the ability
      of RP-HPLC to separate Ile- and allo-Ile-substituted analogs of a 26-residue
      alpha-helical antimicrobial peptide (AMP), with the substitution site towards the
      C-terminus of the alpha-helix. These peptides show different values of
      antibacterial activity and hemolytic activity, and different selectivity against
      bacteria and human cells. Our results underline the ability of RP-HPLC to resolve
      even difficult diasteromeric peptide mixtures as well as its value in monitoring
      very subtle hydrophobicity changes in de novo-designed AMP.

PMID- 24127256
TI  - Developmental and genetic perspectives on Pierre Robin sequence.
AB  - Pierre Robin sequence (PRS) is a craniofacial anomaly comprising mandibular
      hypoplasia, cleft secondary palate and glossoptosis leading to life-threatening
      obstructive apnea and feeding difficulties during the neonatal period. The
      respiratory issues require careful management and in severe cases may require
      extended stays in neonatal intensive care units and surgical intervention such as
      lengthening the lower jaw or tracheotomy to relieve airway obstruction. These
      feeding and respiratory complications frequently continue well into childhood,
      affecting not only growth and development but also impacting on long term
      educational attainment. The diagnosis of PRS depends on readily recognizable
      clinical features but the phenotypic similarity of many PRS individuals conceals
      considerable etiological heterogeneity. Defects in the growth of the mandible sit
      at the core of PRS and the natural history of PRS can be classified into two
      major streams: primary defects of mandibular outgrowth and elongation and issues
      that are external to the mandibular skeleton but that secondarily impact on its
      growth. These altered developmental trajectories appear to be driven by a range
      of influences including defects in cartilage growth, neuromuscular function and
      fetal constraint. Various genetic and cytogenetic associations have been made
      with PRS and the diversity of these associations highlights the fact that there
      are numerous ways to arrive at this common phenotypic endpoint.

PMID- 24127257
TI  - Which factors predict proposal and uptake of psychological counselling after
      BRCA1/2 test result disclosure?
AB  - OBJECTIVE: The aim of this study is to prospectively determine the factors
      contributing to whether unaffected women from BRCA1/2 families reported that
      clinicians proposed psychological consultations and that they had attended these
      consultations during the genetic testing process. METHODS: A prospective study
      was performed on a national cohort, using self-administered questionnaires to
      determine the rates of proposal and use of psychological services at the time of
      BRCA1/2 test result disclosure (N = 533) and during the first year after
      disclosure (N = 478) among unaffected French women from BRCA1/2 families who had
      undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out
      using logistic regression models fitted using generalized estimation equations,
      with the genetic testing centre as the clustering variable. RESULTS: At the time
      of BRCA1/2 test result disclosure, a psychological consultation was proposed by
      cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N =
      301), respectively (p < 0.001). One year after disclosure, 21% of the carriers
      had consulted a psychologist, versus 9% of the noncarriers (p < 0.001). Both the
      proposal and the uptake depended on the women's BRCA1/2 mutation carrier status
      (proposal adjusted odds ratio (AOR): 4.9; 95% confidence interval (CI) 3.4-7.2;
      uptake AOR: 2.2; 95% CI 1.2-4.0), their level of education (proposal AOR: 1.7;
      95% CI 1.1-2.7; uptake AOR: 4.5; 95% CI 1.7-12.1) and the distress they
      experienced about their genetic test results (proposal AOR: 1.02; 95% CI 1.01
      1.03; uptake AOR: 1.04; 95% CI 1.02-1.06) CONCLUSIONS: Determinants of the
      proposal/uptake of psychological consultations in the BRCA1/2 testing process
      highlight the need for inventive strategies to reach the different types of
      women's profiles.

PMID- 24127258
TI  - Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity.
AB  - The NS5A protein plays a critical role in the replication of HCV and has been the
      focus of numerous research efforts over the past few years. NS5A inhibitors have
      shown impressive in vitro potency profiles in HCV replicon assays, making them
      attractive components for inclusion in all oral combination regimens. Early work
      in the NS5A arena led to the discovery of our first clinical candidate, MK-4882
      [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin-2-yl)-1H-imidazol-2
      yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical proof-of-concept
      studies in HCV-infected chimpanzees harboring chronic genotype 1 infections
      resulted in significant decreases in viral load after both single- and multiple
      dose treatments, viral breakthrough proved to be a concern, thus necessitating
      the development of compounds with increased potency against a number of genotypes
      and NS5A resistance mutations. Modification of the MK-4882 core scaffold by
      introduction of a cyclic constraint afforded a series of tetracyclic inhibitors,
      which showed improved virologic profiles. Herein we describe the research efforts
      that led to the discovery of MK-8742, a tetracyclic indole-based NS5A inhibitor,
      which is currently in phase 2b clinical trials as part of an all-oral, interferon
      free regimen for the treatment of HCV infection. 

PMID- 24127259
TI  - The availability, pricing and affordability of three essential asthma medicines
      in 52 low- and middle-income countries.
AB  - BACKGROUND: Almost 300 million people suffer from asthma, yet many in low- and
      middle-income countries have difficulty accessing essential asthma medicines.
      Availability, price and affordability of medicines are likely to affect access.
      Very few studies have included asthma medicines, particularly inhaled
      corticosteroids, in these countries. Reflections about international reference
      prices (IRPs) are generally absent from pricing studies, yet some IRPs may be
      masking the extent of access problems. OBJECTIVES: Our objective was to determine
      the availability, pricing and affordability of beclometasone, budesonide and
      salbutamol, the three asthma medicines on the World Health Organization's Model
      List of Essential Medicines (EML) in selected low- and middle-income countries
      and to reflect on the appropriateness of using IRPs. METHODS: A cross-sectional
      pricing survey was conducted in 52 countries. Data were collected on country
      demographics including national currency, $US exchange rate and daily wage of the
      lowest-paid unskilled government worker. Pricing and availability data were
      collected for salbutamol, beclometasone and budesonide in two private retail
      pharmacies, the national procurement centre and a main public hospital. RESULTS:
      Availability was particularly poor for corticosteroids, and worse in national
      procurement centres and main hospitals. The surveyed strength of beclometasone
      was only on the EML of ten countries. Considerable variability was found in
      pricing and affordability across countries. Procurement systems appeared largely
      inefficient when Asthma Drug Facility prices were applied as references. Some
      countries appear to be subsidising asthma medicines, making them free or less
      expensive for patients, while other countries are applying very high margins,
      which can significantly increase the price for patients unless a reimbursement
      system exists. CONCLUSIONS: Findings raise important policy concerns.
      Availability of inhaled corticosteroids is poor; many EMLs are not updated; IRPs
      can be misleading; health systems and patients are paying more than necessary for
      asthma medicines, which are unaffordable for many patients in many countries.

PMID- 24127260
TI  - Causes of retrograde flow in fish keratocytes.
AB  - Confronting motile cells with obstacles doubling as force sensors we tested the
      limits of the driving actin and myosin machinery. We could directly measure the
      force necessary to stop actin polymerization as well as the force present in the
      retrograde actin flow. Combined with detailed measurements of the retrograde flow
      velocity and specific manipulation of actin and myosin we found that actin
      polymerization and myosin contractility are not enough to explain the cells
      behavior. We show that ever-present depolymerization forces, a direct entropic
      consequence of actin filament recycling, are sufficient to fill this gap, even
      under heavy loads.

PMID- 24127261
TI  - Asymptomatic hematuria associated with urinary polyomavirus infection in
      immunocompetent patients.
AB  - Unlike the case for immunodeficient patients, little is known about polyomavirus
      (PV) infection in immunocompetent patients. PV infection in immunocompetent
      individuals has been reported sporadically, but little is known about
      asymptomatic hematuria. To determine the clinical significance and prevalence of
      urinary PV infection in immunocompetent patients, a total of 95 individuals
      admitted to Seoul St. Mary's hospital were investigated. Sixty-four patients were
      enrolled for evaluation of asymptomatic hematuria, and 31 healthy individuals
      served as controls. Clinical screening for PV infection was performed by urine
      cytology analysis by liquid-based preparation and urine RT-PCR for BK virus (BKV)
      and JC virus (JCV), respectively. The average age of the patients in the PV(+) -
      and PV(-) -groups with asymptomatic hematuria were 60 years and 46 years,
      respectively. Urine cytology analysis revealed decoy cells in 37/64 hematuria
      patients (38.9%), but not in healthy controls. They were more prevalent in male
      patients. Eighty-two patients (86.3%) had PV viruria, viz., 54/64 patients in the
      hematuria group and 28/31 in the control group. Interestingly, 28/31 (90.3%)
      cases in the healthy control group were positive for PV viruria, which exceeded
      the number in the hematuria group (84.4%). PV viruria was associated primarily
      with JCV, rather than BKV. PV viruria, including JCV viruria, correlated with
      urine decoy cells and increased age. In conclusion, urinary PV infection is
      common in immunocompetent patients with asymptomatic hematuria and is age
      related. These data may provide an insight into the pathogenesis and future
      treatment of asymptomatic hematuria associated with urinary PV infection in
      immunocompetent patients.

PMID- 24127263
TI  - Enantioselective copper-catalyzed conjugate addition of trimethylaluminum to
      beta,gamma-unsaturated alpha-ketoamides: efficient access to gamma-methyl
      substituted carbonyl compounds.

PMID- 24127264
TI  - Showcasing Differences Between Quality Improvement, Evidence-Based Practice, and
      Research.

PMID- 24127266
TI  - Exploring the viability of using online social media advertising as a recruitment
      method for smoking cessation clinical trials.
AB  - INTRODUCTION: The aim of the present study was to explore the viability of using
      social media as a recruitment tool in a clinical research trial. Sociodemographic
      data and smoking characteristics were assessed in 266 participants recruited to
      investigate the effectiveness of a behavioral support program for smoking
      cessation. METHODS: For analysis, participants were separated into 2 groups based
      on whether they were recruited either using traditional means (flyers, word of
      mouth, or newspaper advertisement; n = 125, 47.0%) or by advertisements in online
      social media (n = 138, 51.9%). RESULTS: Participants recruited via social media
      were significantly younger, but there were no differences in other socioeconomic
      variables or smoking characteristics compared with participants recruited via
      other traditional means. CONCLUSIONS: The findings of the present study suggest
      that using online social media is a viable recruitment method for smoking studies
      and compliments other more traditional recruitment methods.

PMID- 24127265
TI  - Factors associated with smoking cessation in early and late pregnancy in the
      smoking, nicotine, and pregnancy trial: a trial of nicotine replacement therapy.
AB  - INTRODUCTION: Previous studies have found partners' smoking status, multiparity,
      and nicotine dependence to be associated with smoking cessation in pregnancy.
      However, no studies have investigated influences on cessation among women using
      nicotine replacement therapy (NRT). We analyzed data from a trial of NRT in
      pregnancy to determine factors associated with shorter- and longer-term
      cessation. METHODS: Data were collected at baseline, 1 month, and delivery from
      1,050 pregnant women. Two multivariable logistic models for validated cessation
      at 1 month and delivery were created with a systematic strategy for selection of
      included factors. RESULTS: All findings are from multivariable analyses. At 1
      month, odds of cessation were greater among those who completed full time
      education at >16 years of age (odds ratio [OR] = 1.82, 95% confidence interval CI
      = 1.24-2.67, p = .002) but they were lower in women with higher baseline cotinine
      levels (OR = 0.93, 95% CI = 0.90-0.95, p < .001). At delivery, the odds of
      cessation were greater among those who completed full time education at >16 years
      of age (OR = 1.89, 95% CI = 1.16-3.07, p = 0.010) but were inversely associated
      with higher baseline cotinine levels (OR = 0.96, 95% CI = 0.92-0.99, p = .010).
      CONCLUSIONS: Women who are better educated and have lower pretreatment cotinine
      concentrations had higher odds of stopping smoking and factors associated with
      shorter and longer term cessation were similar.

PMID- 24127267
TI  - A positive feedback loop between STAT3 and cyclooxygenase-2 gene may contribute
      to Helicobacter pylori-associated human gastric tumorigenesis.
AB  - Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric
      diseases including chronic gastritis and gastric cancer. However, the
      pathogenesis of this carcinogenic bacterium has not been completely elucidated.
      Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3
      dependent COX-2 expression both in vitro and in vivo. STAT3 upregulates COX-2 by
      binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates
      IL-6/STAT3 signaling under basal conditions and during H. pylori infection. These
      findings suggest that a positive feedback loop between STAT3 and COX-2 exists in
      the basal condition and H. pylori infectious condition. Immunohistochemical
      staining revealed that H. pylori-positive gastritis tissues exhibited markedly
      higher levels of pSTAT3(Tyr705) than H. pylori-negative ones. High pSTAT3(Tyr705)
      levels are correlated with intestinal metaplasia and dysplasia, suggesting
      pSTAT3(Tyr705) may be useful in the early detection of gastric tumorigenesis.
      Additionally, a strong positive correlation between STAT3/pSTAT3(Tyr705) levels
      and COX-2 expression was identified in gastritis and gastric cancer tissues.
      Together, these findings provide new evidence for a positive feedback loop
      between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new
      approaches for early detection and effective therapy of gastric cancer

PMID- 24127268
TI  - Prevalence of vitamin D deficiency in patients with foot and ankle injuries.
AB  - BACKGROUND: Vitamin D deficiency has been identified as one of the most common
      causes of fragility fractures and poor fracture healing. Although rates of
      vitamin D deficiency have been delineated in various orthopaedic populations,
      little is known about the prevalence of vitamin D deficiency in patients with
      foot and ankle disorders. The goal of this study was to identify the prevalence
      of vitamin D deficiency in patients with a low energy fracture of the foot or
      ankle. METHODS: Over a 6-month period, a serum 25-OH vitamin D level was obtained
      from consecutive patients with a low energy ankle fracture, fifth metatarsal base
      fracture, or stress fracture of the foot or ankle. For comparative purposes,
      vitamin D levels in patients with an ankle sprain and no fracture were also
      examined. RESULTS: The study cohort included 75 patients, of which 21 had an
      ankle fracture, 23 had a fifth metatarsal base fracture, and 31 had a stress
      fracture. The mean age was 52 (range, 16-80) years. Thirty-five of the fracture
      patients (47%) had an insufficient vitamin D level (below the recommended level
      of 30 ng/mL), and 10 of the patients (13%) had a level that was deficient (< 20
      ng/mL). Vitamin D levels were significantly lower in those with a fracture than
      in those with an ankle sprain (P = .02). In the fracture cohort, the factors
      significantly associated with vitamin D insufficiency in the multivariate
      analysis were smoking (P = .03), obesity (P = .003), and other medical risk
      factors for vitamin D deficiency (P = .03). CONCLUSION: Hypovitaminosis D was
      common among patients with a foot or ankle injury seen at our institution.
      Patients with a low energy fracture of the foot or ankle were at particular risk
      for low vitamin D, especially if they smoked, were obese, or had other medical
      risk factors. Given that supplementation with vitamin D (+/- calcium) has been
      shown to reduce the risk of fragility fractures and improve fracture healing,
      monitoring of 25-OH vitamin D and supplementation should be considered in
      patients with fractures. LEVEL OF EVIDENCE: Level III, prospective case control.

PMID- 24127269
TI  - Non-contrast 3D MR lymphography of retroperitoneal lymphatic aneurysmal
      dilatation: a continuous spectrum of change from normal variants to cystic
      lymphangioma.
AB  - OBJECTIVE: Our objective was to demonstrate the characteristic features of
      retroperitoneal lymphatic aneurysmal dilatation with three-dimensional (3D)
      magnetic resonance (MR) lymphography. CONCLUSION: Three-dimensional MR
      lymphography demonstrates that retroperitoneal lymphatic aneurysmal dilatation
      exhibits a continuous spectrum of change from normal variants to lymphatic
      aneurysmal dilatation and so-called cystic lymphangioma. MAIN MESSAGE: * Non
      contrast MR lymphography with very heavily T2-weighted fast spin echo sequences
      is a useful non-invasive technique without the need of contrast medium injection
      to obtain a unique evaluation of the lymphatic system * To prove the lymphatic
      origin of a cystic formation, it is essential to demonstrate the communication
      with retroperitoneal lymphatic vessels * 3D MR lymphography demonstrates that
      retroperitoneal lymphatic aneurysmal dilatation exhibits a continuous spectrum of
      change from normal variants to lymphatic aneurysmal dilatation and so-called
      cystic lymphangioma.

PMID- 24127270
TI  - The strategy of ESR and Insights into Imaging regarding the application for an
      impact factor.

PMID- 24127273
TI  - The pre-treatment prevalence and types of sexual dysfunction among patients
      diagnosed with prostate cancer.
AB  - Erectile dysfunction (ED) following prostate cancer therapy is a common condition
      that is well documented in literature. Despite the significant focus placed on ED
      and prostate cancer, very little is known regarding the baseline prevalence of
      other aspects of sexual dysfunction (SD) in this specific cohort of patients. The
      objective of the current manuscript was to assess the prevalence of subtypes of
      SD, including ED, ejaculatory dysfunction (EjD) and decreased libido among men
      with newly diagnosed prostate cancer. To achieve this objective, patients
      presenting to our clinic with a new diagnosis of prostate cancer from July 2011
      and May 2012 completed the Male Sexual Health Questionnaire (MSHQ) to assess
      baseline sexual function. A total of 60 patients completed an MSHQ, with a mean
      age of 60.28 +/- 6.25 (range 44-73 years). Of patients surveyed, 14% reported no
      sexual activity within the previous month, while 53% had sex at least once
      weekly. The percentage of patients reporting ED, EjD and decreased sexual desire
      >=50% of the time was 37, 26 and 48% respectively. Eleven to 18% of patients
      reported that these symptoms were 'very' or 'extremely' bothersome. Patients
      noted dissatisfaction with the quality of their sexual relationship, frequency of
      sexual activity and quality of sex in 18, 31 and 20%, respectively. Overall
      findings suggest that patients with newly diagnosed prostate cancer experience a
      high rate of SD at baseline. Knowledge of these prevalence rates may assist
      physicians managing patient's expectations with planned therapies. 

PMID- 24127271
TI  - Imaging in rheumatology: reconciling radiology and rheumatology.
AB  - Imaging in rheumatology was in the past largely confined to radiographs of the
      hands and sacroiliac joints (SIJs) helping to establish the diagnosis and then
      monitoring disease progression. Radiographs are not very sensitive for early
      inflammation in inflammatory rheumatic disorders and the demand on imaging
      services was therefore limited. However, over the last 10-15 years new drugs and
      new technologies have brought new challenges and opportunities to rheumatology
      and radiology as specialties. New drug treatments allow more effective treatment,
      preventing many complications. Early diagnosis and disease monitoring has become
      the challenge for the rheumatologist and radiologist alike. The best possible
      patient outcome is only achieved if the two specialties understand each other's
      viewpoint. This article reviews the role of imaging-in particular radiography,
      magnet resonance imaging, computer tomography, ultrasound and nuclear medicine
      for the diagnosis and monitoring of rheumatological disorders, concentrating on
      rheumatoid arthritis, inflammatory spondylarthropathies and gout. Teaching Points
      * New drugs for the treatment of inflammatory disorders has led to greatly
      improved outcomes. * Imaging often allows for earlier diagnosis of inflammatory
      disorders. * Early diagnosis and treatment can often prevent the development of
      crippling disease manifestations. * Tailored imaging examinations are best
      achieved by consultation of rheumatologist and radiologist. 

PMID- 24127274
TI  - Timing of cranial suture closure in placental mammals: phylogenetic patterns,
      intraspecific variation, and comparison with marsupials.
AB  - Used as markers of postnatal growth closure sequences of 22 ectocranial sutures
      and synchondroses were recorded in a sample of 1161 skulls belonging to 38
      species from all major placental clades: Afrotheria, Xenarthra, Laurasiatheria
      and Euarchontoglires (Boreoeutheria). The maximum closure level, which is not
      significantly correlated to body mass, is higher in Afrotheria and Xenarthra than
      in Boreoeutheria. Only the basioccipito-basisphenoid and the basioccipito
      exoccipital synchondroses close in all species sampled, the supraoccipito
      exoccipital and the inter-parietal sutures do in most species. Parsimov retrieved
      more heterochronic shifts for Afrotheria and Xenarthra than for Boreoeutheria.
      The amount of intraspecific variation differs among the species sampled being
      high among xenarthran species and low among afrotherians. Specimens (162)
      representing 12 marsupial genera were also analysed. Placentals exhibit a larger
      number of suture closures than marsupials and in both groups the sutures at the
      base of the skull are the first to fuse starting with the basioccipito
      exoccipital.

PMID- 24127275
TI  - Origin of the superior performance of (thio)squaramides over (thio)ureas in
      organocatalysis.
AB  - The Diels-Alder cycloaddition of anthracene and nitrostyrene catalyzed by the
      squaramide-derived aminocatalysts (Sq) recently reported by Jorgensen and co
      workers (Angew. Chem. 2012, 124, 10417; Angew. Chem. Int. Ed. 2012, 51, 10271)
      has been studied by using modern tools of computational quantum chemistry. This
      catalyst is compared with analogous urea-, thiourea-, and thiosquaramide-derived
      aminocatalysts. Ultimately, a thiosquar-amide-derived catalyst is predicted to
      result in the lowest free-energy barrier, while retaining the same high degree of
      enantioselectivity as Sq. This stems in part from the superior hydrogen-bonding
      ability of thiosquaramides, compared to squaramides and (thio)ureas. We also
      examine the hydrogen-bonding ability of (thio)ureas and (thio)-squaramides in
      model complexes. In contrast to previous work, we show that aromaticity does not
      contribute significantly to the enhanced hydrogen-bonding interactions of
      squaramides. Overall, thiosquaramide, which has not been explored in the context
      of either organocatalysis or molecular recognition, is predicted to lead to
      strong, co-planar hydrogen bonds, and should serve as a potent hydrogen-bonding
      element in a myriad of applications.

PMID- 24127276
TI  - Small-molecule modulators for epigenetics targets.
AB  - A capital conference: Influencing epigenetic mechanisms may be highly relevant
      for future therapies of various diseases such as cancer, inflammation, and
      metabolic disorders. Leading experts in the field gathered in Berlin on June 5-6,
      2013 at a Bayer HealthCare Life Science Workshop to share recent success stories
      and to discuss future trends. 

PMID- 24127278
TI  - Registered Nurses' Perspectives on the New Graduate Working in the Emergency
      Department or Critical Care Unit.

PMID- 24127277
TI  - Genotype and clinical care correlations in craniosynostosis: findings from a
      cohort of 630 Australian and New Zealand patients.
AB  - Craniosynostosis is one of the most common craniofacial disorders encountered in
      clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30%
      and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the
      fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the
      difference in detection rates likely to be related to different study populations
      within craniofacial centers. Here we present results from molecular testing of an
      Australia and New Zealand cohort of 630 individuals with a diagnosis of
      craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and
      FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of
      TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations
      (36%). Among the 80 mutations, 17 novel sequence variants were detected in three
      of the four genes screened. In addition to the proband cohort there were 96
      individuals who underwent predictive or prenatal testing as part of family
      studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated
      syndromes were predictive for mutation detection. We also show a statistically
      significant association between splice site mutations in FGFR2 and a clinical
      diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with
      FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in
      the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation
      analysis is a useful strategy to maximize the success of molecular diagnosis for
      individuals with craniosynostosis.

PMID- 24127279
TI  - Evaluation and treatment recommendations for acute injuries to the ankle
      syndesmosis without associated fracture.
AB  - Ankle ligamentous injuries are commonly seen in athletes in a variety of sports.
      Surveys of physicians and trainers of professional sports teams have identified
      syndesmotic injuries as among the most difficult to treat. In particular,
      injuries of the ankle syndesmosis have been strongly linked with a prolonged
      recovery and increased time to return to play. Due to sudden external rotation
      with the tibiotalar joint in dorsiflexion, these structures are commonly injured
      in association with fractures of the distal fibula. Surgery is indicated in cases
      with associated fractures and ligamentous instability, but optimal treatment for
      syndesmosis injuries without an associated fracture is less clear. A thorough
      history and physical examination, as well as appropriate imaging, are necessary
      to effectively diagnose and classify the injury. For stable injuries, short-term
      immobilization and functional rehabilitation is recommended. Unstable Grade 2 and
      3 injuries require surgical fixation. Debate currently exists over rigid screw
      fixation versus suture button techniques as the ideal fixation method. 

PMID- 24127280
TI  - Large scale study of HPV genotypes in cervical cancer and different cytological
      cervical specimens in Thailand.
AB  - Identification of high-risk HPV genotypes in patients is essential for
      vaccination and prevention programs while the geographic distribution of cervical
      cancer varies widely. HPV 16 is the major cause of cervical cancer followed by
      HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study,
      the distribution of HPV genotypes in cervical specimens from women living in
      Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct
      sequencing. The 716 specimens were grouped according to their cytological grades;
      100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade
      squamous intraepithelial lesions, and 416 specimens of cervical cancer. The
      results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV
      genotypes in Thailand, respectively. With respect to age, women below the age of
      26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high
      prevalence of high-risk HPV DNA and abnormal cytology were usually found in women
      between 26 and 45 years while cervical cancer was detected mainly in women above
      the age of 45 years. To increase protection efficiency, a vaccine including HPV
      52 and HPV 58 should be offered to Asian women, and primary HPV screening should
      start at 26-30 years of age.

PMID- 24127281
TI  - Observing the formation and the reactivity of an octahedral iron(V) nitrido
      complex in real time.
AB  - Give me five: Time-resolved Fourier-transform IR spectroscopy is used to time
      resolve the formation and the reaction dynamics of a fourfold symmetrical nitrido
      iron(V) complex (light blue C, red Fe, blue N) in liquid solution under
      physiological and technologically relevant conditions. 

PMID- 24127282
TI  - The FOXE1 locus is a major genetic determinant for familial nonmedullary thyroid
      carcinoma.
AB  - Thyroid cancer is the most common endocrine malignancy and nonmedullary thyroid
      carcinoma (NMTC) represents 90% of all cases. NMTC risk in first-degree relatives
      of affected cases is elevated fivefold to ninefold. Familial NMTC (FNMTC)
      accounts for about 3-7% of all thyroid tumors and is a more aggressive clinical
      entity than its sporadic counterparts. Linkage analysis on high-risk families
      performed a decade ago mapped several susceptibility loci, but did not lead to
      the identification of high-penetrance causal germline mutations. More recently, a
      genome-wide association study (GWAS) identified common single nucleotide
      polymorphisms (SNPs) affecting the risk of sporadic NMTC. We sought to verify if
      the newly identified genetic risk factors for NMTC are relevant for FNMTC as
      well. We genotyped 23 SNPs at 11 candidate loci in 672 subjects belonging to 133
      pedigrees with at least two NMTC cases. Statistical analysis was performed using
      family-based association tests, modified quasi-likelihood score and logistic
      normal models. SNPs at 9q22.33 near FOXE1 showed convincing evidence of
      association with NMTC risk in these high-risk families. The other tested loci
      resulted negative. These findings confirm the importance of the SNPs identified
      by recent GWAS on sporadic NMTC on FNMTC as well. However, the proposed FOXE1
      causal variants do not show the strongest association signal. Moreover, mutation
      screening of the FOXE1 coding sequence in the FNMTC cases did not identify rarer
      causal variants, suggesting that other yet unidentified variants at this locus
      are involved in FNMTC etiology. 

PMID- 24127283
TI  - Resegmentation in the Mexican axolotl, Ambystoma mexicanum.
AB  - The segmental series of somites in the vertebrate embryo gives rise to the axial
      skeleton. In amniote models, single vertebrae are derived from the sclerotome of
      two adjacent somites. This process, known as resegmentation, is well-studied
      using the quail-chick chimeric system, but the presumed generality of
      resegmentation across vertebrates remains poorly evaluated. Resegmentation has
      been questioned in anamniotes, given that the sclerotome is much smaller and
      lacks obvious differentiation between cranial and caudal portions. Here, we
      provide the first experimental evidence that resegmentation does occur in a
      species of amphibian. Fate mapping of individual somites in the Mexican axolotl
      (Ambystoma mexicanum) revealed that individual vertebrae receive cells from two
      adjacent somites as in the chicken. These findings suggest that large size and
      segmentation of the sclerotome into distinct cranial and caudal portions are not
      requirements for resegmentation. Our results, in addition to those for zebrafish,
      indicate that resegmentation is a general process in building the vertebral
      column in vertebrates, although it may be achieved in different ways in different
      groups.

PMID- 24127285
TI  - Real Sociedad Espanola de Quimica prizes 2013.

PMID- 24127287
TI  - Tris(tetraceno)triquinacenes: synthesis and photophysical properties of threefold
      linearly extended tribenzotriquinacenes.
AB  - The linear extension of the rigid, C(3v)-symmetrical carbon framework of
      tribenzotriquinacene (TBTQ) along its three wings is reported. The key step of
      the extension procedure consists of a Diels-Alder reaction of three ortho
      quinodimethane units generated in situ at the triquinacene core. The use of 1,4
      naphthoquinone provides a facile and particularly efficient access to
      tris(tetraceno)-annellated triquinacenes. The steady-state photophysical
      properties of these new oligotetracenes bearing three mutually orthogonal
      chomophores are determined and analyzed by DFT calculations.

PMID- 24127286
TI  - Silymarin suppresses the PGE2 -induced cell migration through inhibition of EP2
      activation; G protein-dependent PKA-CREB and G protein-independent Src-STAT3
      signal pathways.
AB  - Silymarin has been known as a chemopreventive agent, and possesses multiple anti
      cancer activities including induction of apoptosis, inhibition of proliferation
      and growth, and blockade of migration and invasion. However, whether silymarin
      could inhibit prostaglandin (PG) E2 -induced renal cell carcinoma (RCC) migration
      and what are the underlying mechanisms are not well elucidated. Here, we found
      that silymarin markedly inhibited PGE2 -stimulated migration. PGE2 induced G
      protein-dependent CREB phosphorylation via protein kinase A (PKA) signaling, and
      PKA inhibitor (H89) inhibited PGE2 -mediated migration. Silymarin reduced PGE2 
      induced CREB phosphorylation and CRE-promoter activity. PGE2 also activated G
      protien-independent signaling pathways (Src and STAT3) and silymarin reduced PGE2
      -induced phosphorylation of Src and STAT3. Inhibitor of Src (Saracatinib)
      markedly reduced PGE2 -mediated migration. We found that EP2, a PGE2 receptor, is
      involved in PGE2 -mediated cell migration. Down regulation of EP2 by EP2 siRNA
      and EP2 antagonist (AH6809) reduced PGE2 -inudced migration. In contrast, EP2
      agonist (Butaprost) increased cell migration and silymarin effectively reduced
      butaprost-mediated cell migration. Moreover, PGE2 increased EP2 expression
      through activation of positive feedback mechanism, and PGE2 -induced EP2
      expression, as well as basal EP2 levels, were reduced in silymarin-treated cells.
      Taken together, our study demonstrates that silymarin inhibited PGE2 -induced
      cell migration through inhibition of EP2 signaling pathways (G protein dependent
      PKA-CREB and G protein-independent Src-STAT3).

PMID- 24127288
TI  - Frequency of sexual activity and cardiovascular risk in subjects with erectile
      dysfunction: cross-sectional and longitudinal analyses.
AB  - Erectile dysfunction (ED) is risk factor for cardiovascular (CV) events. The
      relationship between sexual activity and incident major adverse cardiovascular
      events (MACE) in subjects at high CV risk is conflicting and never investigated
      in ED subjects. The aim of this study was to investigate relationships between
      frequency of sexual attempts and incident MACE and to retrospectively explore its
      main determinants in subjects with sexual dysfunction. A consecutive series of
      2187 subjects (mean age 49.9 +/- 11.6 years old) attending the Outpatient Clinic
      for sexual dysfunction was retrospectively studied. A subset of the previous
      sample (N = 1687) was enrolled in a longitudinal study. Frequency of sexual
      intercourse (coital and non-coital) was assessed using a standard question
      ('During the last 3 months how many sexual attempts per month did you have?'). In
      the whole sample, sexual attempts were an age- and testosterone-dependent
      phenomenon, while no association between frequency of sexual intercourse and ED
      or premature and delayed ejaculation, was observed. However, when the same
      analysis was performed according to age tertiles (I = 17-46, II = 47-59, III = 60
      88 years old), ED was significantly associated with a higher risk of reduced
      sexual intercourse in younger (hazard ratio = 1.857 [1.066-3.234]; p = 0.029),
      but not in middle-aged or older individuals. The marital component, as assessed
      by SIEDY Scale 2, played a major role in regulating sexual frequency in all age
      bands. Depressive symptoms represent another independent risk factor for reduced
      sexual activity (adj r = -0.139; p < 0.0001), in an age-dependent manner. When
      longitudinal data were analysed, a higher frequency of sexual intercourse
      significantly reduced the risk of MACE even after adjusting for known CV risk
      factors for this cohort. Identifying among mild-to-moderate ED subjects those
      with lower frequency of sexual activity might provide an opportunity to modify
      their behaviour and to discover subthreshold comorbidities, possibly preventing
      forthcoming CV events. 

PMID- 24127289
TI  - Rapid and simultaneous detection of vitamin D receptor gene polymorphisms by a
      single ARMS-PCR assay.
AB  - BACKGROUND: Vitamin D has various roles in many biological actions such as
      calcium homeostasis, cell proliferation, and cell differentiation to many target
      tissues. These effects are mediated by the active form of vitamin D, 1,25(OH)2D3,
      which binds to a cytoplasmic protein called vitamin D receptor (VDR). VDR gene
      has four common single nucleotide polymorphisms (SNPs) that are defined by the
      presence of restriction sites for FokI (F/f), TaqI (T/t), BsmI (B/b), and ApaI
      (A/a). The association of VDR gene polymorphisms with several diseases has been
      investigated. In most studies, VDR genotyping was performed by polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) assays, which are
      cumbersome and time consuming, and their results are sometimes difficult to
      interpret. OBJECTIVE: We modified previously reported primers for VDR genotyping
      and set up a single amplification-refractory mutation system (ARMS)-PCR method
      for simultaneous genotyping of four common VDR polymorphisms. METHODS: In this
      study, 218 DNA samples were analyzed for VDR genetic variants by this ARMS-PCR
      technique; 136 of them were re-genotyped by PCR-RFLP assays to compare genotyping
      results. RESULT: We obtained allelic frequencies of 69 vs. 31 % for F/f, 34 vs.
      66 % for B/b, 70 vs. 30 % for T/t, and 52 vs. 48 % for A/a in this sample of the
      Iranian population. In addition, comparisons of the results of these two methods
      showed good uniformity in VDR genotypes; although, in some samples, ambiguity in
      restriction patterns was present. CONCLUSION: As ARMS-PCR is more rapid,
      economic, and user friendly than PCR-RFLP, its substitution would be welcomed in
      disease association and pharmacogenetic studies of VDR variants.

PMID- 24127290
TI  - Significant impact of non-B HIV-1 variants genetic diversity in Gabon on plasma
      HIV-1 RNA quantitation.
AB  - Evaluations of HIV-1 RNA viral load assays are lacking in Central Africa. The
      main objective of our study was to assess the reliability of HIV-1 RNA results
      obtained with three different assays for samples collected in Gabon. A total of
      137 plasma specimens were assessed for HIV-1 RNA using the Abbott RealTime HIV
      1(r) and Nuclisens HIV-1 EasyQ(r) version 2.0 assays. It included HIV-1 non-B
      samples (n = 113) representing six subtypes, 10 CRFs and 18 URFs from patients
      infected with HIV-1 and treated with antiretrovirals that were found HIV-1 RNA
      positive (>=300 copies/ml) with the Generic HIV viral load(r) assay; and samples
      (n = 24) from untreated individuals infected with HIV-1 but showing undetectable
      (<300 copies/ml) results with the Biocentric kit. For samples found positive with
      the Generic HIV viral load(r) test, correlation coefficients obtained between the
      three techniques were relatively low (R = 0.65 between Generic HIV viral load(r)
      and Abbott RealTime HIV-1(r), 0.50 between Generic HIV viral load(r) and
      Nuclisens HIV-1 EasyQ(r), and 0.66 between Abbott RealTime HIV-1(r) and Nuclisens
      HIV-1 EasyQ(r)). Discrepancies by at least one log10 were obtained for 19.6%,
      33.7%, and 20% of samples, respectively, irrespective of genotype. Most of
      samples (22/24) from untreated study patients, found negative with the Biocentric
      kit, were also found negative with the two other techniques. In Central Africa,
      HIV-1 genetic diversity remains challenging for viral load testing. Further
      studies are required in the same area to confirm the presence of HIV-1 strains
      that are not amplified with at least two different viral load assays.

PMID- 24127291
TI  - Reply to Chirumbolo.

PMID- 24127292
TI  - Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and
      dendrimer generation to temperature sensitivity.
AB  - Dendrimers are synthetic macromolecules with unique structure, which are a
      potential scaffold for peptides. Elastin is one of the main components of
      extracellular matrix and a temperature-sensitive biomacromolecule. Previously,
      Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an
      elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers
      using different length peptides and different dendrimer generations were
      synthesized to control the temperature dependency. The elastin-mimetic dendrimers
      formed beta-turn structure by heating, which was similar to the elastin-like
      peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition,
      largely depending on the peptide length and slightly depending on the dendrimer
      generation. The elastin-mimetic dendrimers formed aggregates after the phase
      transition. The endothermal peak was observed in elastin-mimetic dendrimers with
      long peptides, but not with short ones. The peptide length and the dendrimer
      generation are important factors to tune the temperature dependency on the
      elastin-mimetic dendrimer.

PMID- 24127294
TI  - Design and generation of highly diverse fluorinated fragment libraries and their
      efficient screening with improved (19) F NMR methodology.
AB  - Fragment screening performed with (19) F NMR spectroscopy is becoming
      increasingly popular in drug discovery projects. With this approach, libraries of
      fluorinated fragments are first screened using the direct-mode format of the
      assay. The choice of fluorinated motifs present in the library is fundamental in
      order to ensure a large coverage of chemical space and local environment of
      fluorine (LEF). Mono- and poly-fluorinated fragments to be included in the
      libraries for screening are selected from both in-house and commercial
      collections, and those that are ad hoc designed and synthesized. Additional
      fluorinated motifs to be included in the libraries derive from the fragmentation
      of compounds in development and launched on the market, and compounds contained
      in other databases (such as Integrity, PDB and ChEMBL). Complex mixtures of
      highly diverse fluorine motifs can be rapidly screened and deconvoluted in the
      same NMR tube with a novel on the fly combined procedure for the identification
      of the active molecule(s). Issues and problems encountered in the design,
      generation and screening of diverse fragment libraries of fluorinated compounds
      with (19) F NMR spectroscopy are analyzed and technical solutions are provided to
      overcome them. The versatile screening methodology described here can be
      efficiently applied in laboratories with limited NMR setup and could potentially
      lead to the increasing role of (19) F NMR in the hit identification and lead
      optimization phases of drug discovery projects. 

PMID- 24127295
TI  - Catalytic enantioselective Michael addition of alpha-aryl-alpha-isocyanoacetates
      to vinyl selenone: synthesis of alpha,alpha-disubstituted alpha-amino acids and
      (+)- and (-)-trigonoliimine A.

PMID- 24127293
TI  - Biophysically defined and cytocompatible covalently adaptable networks as
      viscoelastic 3D cell culture systems.
AB  - Presented here is a cytocompatible covalently adaptable hydrogel uniquely capable
      of mimicking the complex biophysical properties of native tissue and enabling
      natural cell functions without matrix degradation. Demonstrated is both the
      ability to control elastic modulus and stress relaxation time constants by more
      than an order of magnitude while predicting these values based on fundamental
      theoretical understanding and the simulation of muscle tissue and the
      encapsulation of myoblasts. 

PMID- 24127297
TI  - Notable plesiomorphies and notable specializations: head structure of the
      primitive "tongue moth" Acanthopteroctetes unifascia (Lepidoptera:
      Acanthopteroctetidae).
AB  - The Acanthopteroctetidae are one of the first-originated family-group lineages
      within "tongue moths" (Lepidoptera-Glossata). The purpose of this study is to
      provide a comprehensive account (based on whole mount preparations, serial
      sections, and Scanning electron microscopy) of the cephalic structure of an adult
      exemplar of the family, to supplement the sparse available information. Notable
      plesiomorphies include the retention of frontal retractors of the narrow labrum,
      a high supraocular index linked to strong development of cranio-mandibular ad-
      and abductors, and perhaps the unusually short but still coilable (just ca. 1.5
      turns) galeal "tongue." Notable specializations (probably mostly family
      autapomorphies) include a complement of large sensilla placodea on the male
      antennae, an apical attachment of the long dorsal tentorial arm to the cranium,
      an extreme reduction of the single-segmented labial palps, a particularly strong
      subgenal bridge and a surface structure of near-parallel ridges on the ommatidial
      corneae. The presence of sizable saccular mandibular (type 1) glands opening into
      the adductor apodeme is unexpected, no counterparts being known from neighboring
      taxa. The same is true for ventral salivarium dilator muscles originating on the
      prelabium; and tentatively suggested to be homologues of the extrinsic palp
      flexors (the insertion shift being related to loss of original function due to
      palp reduction), rather than to the ventral salivarium muscles of more basal
      insects. A complete "deutocerebral loop"' may or may not be developed, as is true
      for a mutual appression of the optic lobe and circumoesophageal
      connective/suboesophageal ganglion, enclosing the anterior tentorial arm between
      them; a suboesophageal innervation of the retrocerebral complex was not observed.
      No characters bearing on the monophyly of the Coelolepida were identified. The
      scapo-pedicellar articulation with a scapal process and a smooth intercalary
      sclerite is reminiscent of conditions in Neopseustidae, but remains debatable as
      a synapomorphy of the two families.

PMID- 24127298
TI  - Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in
      patients with solid tumors: a systematic review and meta-analysis of clinical
      trials.
AB  - Gastrointestinal (GI) events have been described with sorafenib, sunitinib and
      pazopanib in cancer patients. We performed an up-to-date meta-analysis to
      determine the incidence and relative risk (RR) in patients with cancer treated
      with these agents. PubMed databases were searched for articles published till May
      2013. Eligible studies were selected according to PRISMA statement. Summary
      incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects
      models based on the heterogeneity of selected studies. A total of 6,447 patients
      were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and
      4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066
      breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors
      and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When
      stratified by tumor type (RCC vs. non-RCC), the difference among the incidences
      of GI events was significant for diarrhea (p < 0.001) and vomiting (p = 0.006),
      that resulted higher in RCC patients. In RCC patients, sorafenib registered the
      lower incidence and RR of all grades GI events. The difference was statistically
      significant for sorafenib versus sunitinib-related all and high-grade events (p <
      0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and
      high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib
      and pazopanib is associated with a significant increase in the risk of GI events
      in patients with cancer, and frequent clinical monitoring should be emphasized
      when managing these three and newer VEGFR TKIs. 

PMID- 24127299
TI  - New Fe(I) -Fe(I) complex featuring a rotated conformation related to the [2
      Fe](H) subsite of [Fe-Fe] hydrogenase.
AB  - Rotated geometry: The first example of a dinuclear iron(I)-iron(I) complex
      featuring a fully rotated geometry related to the active site of [Fe-Fe]
      hydrogenase is reported. 

PMID- 24127300
TI  - Using videovoice methods to enhance community outreach and engagement for the
      National Children's Study.
AB  - The National Children's Study (NCS) is a prospective observational study
      examining the effects of environmental influences on child health and development
      in the United States. Videovoice is a health advocacy and promotion methodology
      wherein participants use participatory videography and interviewing techniques to
      identify issues of concern, communicate knowledge, and advocate for community
      health. This study describes a videovoice project, implemented in six Cook
      County, IL, communities targeted by the NCS for participant recruitment. A 6
      week, videovoice training was conducted to train and empower NCS community
      outreach and engagement personnel. Pre/post evaluations were administered, and
      participant footage was qualitatively analyzed to identify overarching themes
      informing future outreach. Participants reported significant increases (p < .05)
      in videography/photography skills, community outreach/communication abilities,
      and awareness of important community health issues. Major themes included the
      following: high community knowledge of local health issues, low community
      knowledge of the NCS, and identification of barriers to participation. Two
      promotional videos were created to address these barriers and educate communities
      about the NCS. A 6-week, videovoice project was effective in training NCS
      community outreach personnel and enhancing NCS community engagement within six
      target Cook County, IL, communities via the production of community-engaged NCS
      promotional videos. 

PMID- 24127301
TI  - Implementation of a tailored kiosk-based injury prevention program in pediatric
      primary care.
AB  - This study identified behavioral and organizational barriers and facilitators
      related to the implementation of a clinic-based pediatric injury prevention
      program. Safe N' Sound (SNS), an evidence-based tailored injury prevention
      program designed for pediatric primary care, was implemented in five pediatric
      clinics in North Carolina. Office managers participated in structured interviews;
      health care providers participated in focus groups. Waiting room observations
      were conducted in participating clinics. Qualitative data captured perceptions of
      program implementation, including experience in integrating the program into
      clinical practice, usage by parents and providers, and recommendations for
      improving implementation. Reported facilitators of program use included
      usefulness and likeability of customized materials by parents and physicians and
      alignment with clinic priorities for injury prevention. Barriers included
      perceived staff burden despite the program's low staff requirements.
      Consequently, practices experienced difficulty integrating the program into the
      waiting room environment and within existing staff roles. Recommendations
      included formalizing staff roles in implementation. Waiting room observations
      supported greater technology maintenance and staff involvement. Findings suggest
      a dynamic relationship between program implementation and the adopting
      organization. In addition to considering characteristics of the intervention,
      environment, and personnel in intervention development, implementation may
      require customization to the organization's capacity. 

PMID- 24127302
TI  - Molecular diversity of HIV-1 and surveillance of transmitted drug resistance
      variants among treatment Naive patients, 5 years after active introduction of
      HAART in Kuala Lumpur, Malaysia.
AB  - Expansion of antiretroviral treatment programs have led to the growing concern
      for the development of antiretroviral drug resistance. The aims were to assess
      the prevalence of drug resistant HIV-1 variants and to identify circulating
      subtypes among HAART-naive patients. Plasma specimens from N = 100 HIV+ HAART
      naive adult were collected between March 2008 and August 2010 and viral RNA were
      extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and
      checked for transmitted drug resistance mutations. Phylogenetic reconstruction
      and recombination analysis were performed to determine the genotypes. Based on
      the WHO consensus guidelines, none of the recruited patients had any transmitted
      drug resistance mutations. When analyzed against the Stanford guidelines, 35% of
      patients had at least one reported mutation that may reduce drug susceptibility
      to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may
      affect current first line therapy was V179D (3%), which may lead to reduced
      susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were
      CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms
      (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype
      B' were observed, among them a cluster of three isolates that could form a novel
      circulating recombinant form (CRF) candidate. Transmitted drug resistance
      prevalence among HAART-naive patients was low in this cohort of patients in Kuala
      Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic
      diversity, continued molecular surveillance can identify the persistent emergence
      of HIV-1 URF and novel CRF with significant epidemiological impact.

PMID- 24127303
TI  - Structural characterization and bioactivity evaluation of an acidic proteoglycan
      extract from Ganoderma lucidum fruiting bodies for PTP1B inhibition and anti
      diabetes.
AB  - A water-soluble PTP1B inhibitor, named FYGL-a, was fractionated for structure
      investigation and bioactivity evaluation. FYGL-a is an ingredient of a reported
      antihyperglycemia extract from Ganoderma Lucidum fruiting bodies. Composition
      analysis indicated that FYGL-a was a 100.2 kDa acidic proteoglycan, consisting of
      85 +/- 2% heteropolysaccharide chain with rhamnose, galactose, glucose, and
      glucuronic acid residues in a mole ratio of 1.0:3.7:3.9:2.0, and the 15 +/- 2%
      protein moiety of FYGL-a was covalently bonded to the polysaccharide chain in O
      linkage type via threonine residues. The complete sequence of FYGL-a was
      characterized systematically by periodate oxidation, Smith degradation,
      methylation analysis, (1)H & (13)C 1D NMR, and 2D NMR (HSQC, HMBC, NOESY, COSY, &
      TOCSY). The chemical structure of FYGL-a was determined as following, which may
      play special role in the competitive inhibition of PTP1B and antihyperglycemia
      potency.

PMID- 24127304
TI  - Increasing participation in cervical cancer screening: offering a HPV self-test
      to long-term non-attendees as part of RACOMIP, a Swedish randomized controlled
      trial.
AB  - RACOMIP is a population-based, randomized trial of the effectiveness and cost
      effectiveness of different interventions aimed at increasing participation in a
      well-run cervical cancer screening program in western Sweden. In this article, we
      report results from one intervention, offering non-attendees a high-risk human
      papillomavirus (HPV) self-test. Comparison was made with standard screening
      invitation routine or standard routine plus a telephone call. Women (8,800), aged
      30-62, were randomly selected among women without a registered Pap smear in the
      two latest screening rounds. These women were randomized 1:5:5 to one of three
      arms: 800 were offered a high-risk HPV self-test, 4,000 were randomized to a
      telephone call (reported previously) and 4,000 constituted a control group
      (standard screening invitation routine). Results were based on intention to treat
      analysis and cost-effectiveness was calculated as marginal cost per cancer case
      prevented. The endpoint was the frequency of testing. The total response rate in
      the self-testing arm was 24.5%, significantly higher than in the telephone arm
      (18%, RR 1.36, 95% CI 1.19-1.57) and the control group (10.6%, RR 2.33, 95% CI
      2.00-2.71). All nine women who tested positive for high-risk HPV attended for a
      cervical smear and colposcopy. From the health-care sector perspective, the
      intervention will most likely lead to no additional cost. Offering a self-test
      for HPV as an alternative to Pap smears increases participation among long-term
      non-attendees. Offering various screening options can be a successful method for
      increasing participation in this group. 

PMID- 24127305
TI  - Management of osteoarthritis in general practice in Australia.
AB  - OBJECTIVE: To describe management of osteoarthritis (OA) of the hip (OA-hip) and
      knee (OA-knee) by Australian general practitioners (GPs). METHODS: We analyzed
      data from the Bettering the Evaluation and Care of Health program, from April 1,
      2005 to March 31, 2010. Patient and GP characteristics and encounter management
      data were extracted. Data were classified by the International Classification of
      Primary Care, version 2, and summarized using descriptive statistics and 95%
      confidence intervals around point estimates. RESULTS: There were 489,900 GP
      encounters at which OA was managed (rate of 26.4 per 1,000 encounters). OA-hip
      was managed at a rate of 2.3 per 1,000 encounters (n = 1,106, 8.6% OA) and OA
      knee at a rate of 6.2 per 1,000 (n = 3,058, 23.7% OA). The encounter management
      rate per 1,000 for OA-hip was higher among non-metropolitan dwellers (2.85 per
      1,000 versus 1.97 per 1,000) and lower for non-English-speaking people (1.53 per
      1,000 encounters versus 2.39 per 1,000). The rate for OA-knee was higher for non
      English-speaking background (8.50 per 1,000 encounters versus 6.24 per 1,000) and
      lower among indigenous people (3.16 per 1,000 encounters versus 6.46 per 1,000).
      Referral to an orthopedic surgeon was the most frequently used nonpharmacologic
      management (OA-knee 17.4 per 100 contacts and OA-hip 17.7 per 100), followed by
      advice, education, and counselling. As first-line treatment, medication
      prescription rates (OA-knee 78.7 per 100 contacts and OA-hip 73.2 per 100) were
      substantially higher than rates of lifestyle management (OA-knee 20.7 per 100
      contacts and OA-hip 14.8 per 100). CONCLUSION: OA-hip and OA-knee encounters and
      management differ. Nonpharmacologic treatments as first-line management were low
      compared with pharmacologic management rates, and surgical referral rates were
      high. However, lack of longitudinal data limits definitive assessment of
      appropriateness of care.

PMID- 24127306
TI  - Prognostic value of ZAP-70 expression in chronic lymphocytic leukemia as assessed
      by quantitative polymerase chain reaction and flow cytometry.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a disorder in which the tempo
      of disease progression is highly variable, and prognostic markers that can be
      utilized at diagnosis are regarded as clinically important. Currently, there are
      several prognostic factors, such as immunoglobulin heavy chain (IgVH) mutational
      status, and ZAP-70 protein expression in neoplastic B-cells, that have
      demonstrated significant discriminative power in the prognostication of CLL. They
      are, however, largely unavailable in the routine diagnostic laboratory setting.
      METHODS: In this study, we characterized the IgVH status and ZAP-70 expression by
      molecular techniques in a cohort of 108 patients with CLL, and correlated these
      results with three different methods of ZAP-70 expression by flow cytometry. We
      then assessed the results of these methods in terms of prognostic power as
      characterized by time to first treatment (TTFT). RESULTS: By comparing three
      different flow cytometry methods using receiver-operator curve (ROC) analysis, we
      identified that by utilizing a corrected mean fluorescence intensity (CorrMFI)
      algorithm for assessing ZAP-70 expression, there was good correlation with both
      IgVH mutational status, and ZAP-70 expression as assessed by qPCR. We were also
      able to show that ZAP-70 expression, as assessed by both qPCR and the CorrMFI
      method, was prognostic of TTFT. CONCLUSIONS: While confirmation in a larger
      patient cohort, with longer follow-up is required, we believe that the CorrMFI
      represents the most promising method currently available in a routine diagnostic
      setting for the assessment of ZAP-70 expression in CLL patients.

PMID- 24127307
TI  - Clinical characterization and molecular classification of 12 Korean patients with
      pseudohypoparathyroidism and pseudopseudohypoparathyroidism.
AB  - CONTEXT: Pseudohypoparathyroidism (PHP) is defined as resistance toward
      parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare
      disorders resulting from genetic and epigenetic aberrations within or upstream of
      the GNAS locus. This study investigated the clinical characteristics and
      performed a molecular analysis of PHP and PPHP. METHODS: A total of 12 patients
      with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with
      PPHP) were characterized using both clinical and molecular methods. Clinical
      features included the presenting symptoms, Albright hereditary osteodystrophy
      features, and resistance to hormones. Comprehensive analysis of the GNAS and
      STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP.
      RESULTS: All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients
      showed resistance toward TSH, in addition to PTH. In most patients with PHP, when
      the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia
      were associated with a significant increase in serum PTH levels. One patient with
      PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to
      human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed
      5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss
      of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP
      Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of
      exon A/B on the maternal allele. No patients revealed paternal disomy among 4
      patients with PHP-Ib. CONCLUSIONS: Identification of the molecular causes of PHP
      and PPHP explains their distinctive clinical features and enables confirmation of
      the diagnosis and exact genetic counseling.

PMID- 24127308
TI  - Genetic variants of BANK1 gene in autoimmune thyroid diseases: a case-control
      association study.
AB  - OBJECTIVE: To investigate BANK1 gene variation, and its association with
      autoimmune thyroid disease and clinical features. METHOD: We genotyped 3 single
      nucleotide polymorphisms (SNPs) rs10516487, rs3733197 and rs4522865 of BANK1 gene
      in 667 patients with autoimmune thyroid diseases (417 with Graves' disease and
      250 with Hashimoto's thyroiditis) and 301 healthy controls. The Matrix Assisted
      Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS)
      Platform was used to detect the 3 SNPs. RESULTS: There was a significant
      association in rs3733197 A allele and AITD patients (P=0.043). SNP rs3733197 A
      allele was found in 29.63% chromosome of AITD patients who are 18 years old or
      below, compared with 19.90% chromosome in those 19 years or above (P=0.017). Also
      SNP rs3733197 A allele showed a significant association in HT patients when
      compared with controls (P=0.031, OR=0.73 and 95% CI=0.55-0.97). Stratification
      for specific autoantibodies in AITD patients TGAb positive when compared with SE
      (shared epitope) positive showed a significant association in rs3733197 SNP
      (P=0.010, OR=0.68 and 95%=CI 0.51-0.91). However, no significant association was
      found between 3 SNPs and GD. CONCLUSION: Our findings suggest the existence of
      association between BANK1 gene and AITD thus adding BANK1 gene to the list of the
      predisposing genes to AITD.

PMID- 24127309
TI  - Brain anatomy of the marine tardigrade Actinarctus doryphorus (Arthrotardigrada).
AB  - Knowledge of tardigrade brain structure is important for resolving the
      phylogenetic relationships of Tardigrada. Here, we present new insight into the
      morphology of the brain in a marine arthrotardigrade, Actinarctus doryphorus,
      based on transmission electron microscopy, supported by scanning electron
      microscopy, conventional light microscopy as well as confocal laser scanning
      microscopy. Arthrotardigrades contain a large number of plesiomorphic characters
      and likely represent ancestral tardigrades. They often have segmented body
      outlines and each trunk segment, with its paired set of legs, may have up to five
      sensory appendages. Noticeably, the head carries numerous cephalic appendages
      that are structurally equivalent to the sensory appendages of the trunk segments.
      Our data reveal that the brain of A. doryphorus is partitioned into three paired
      lobes, and that these lobes exhibit a more pronounced separation as compared to
      that of eutardigrades. The first brain lobe in A. doryphorus is located
      anteriodorsally, with the second lobe just below it in an anterioventral
      position. Both of these two paired lobes are located anterior to the buccal tube.
      The third pair of brain lobes are situated posterioventrally to the first two
      lobes, and flank the buccal tube. In addition, A. doryphorus possesses a
      subpharyngeal ganglion, which is connected with the first of the four ventral
      trunk ganglia. The first and second brain lobes in A. doryphorus innervate the
      clavae and cirri of the head. The innervations of these structures indicate a
      homology between, respectively, the clavae and cirri of A. doryphorus and the
      temporalia and papilla cephalica of eutardigrades. The third brain lobes
      innervate the buccal lamella and the stylets as described for eutardigrades.
      Collectively, these findings suggest that the head region of extant tardigrades
      is the result of cephalization of multiple segments. Our results on the brain
      anatomy of Actinarctus doryphorus support the monophyly of Panarthropoda.

PMID- 24127310
TI  - Aptamer-guided caging for selective masking of protein domains.

PMID- 24127311
TI  - Use of a visual analog scale for evaluation of bother from pelvic organ prolapse.
AB  - OBJECTIVES: A specified anatomical degree of prolapse may cause no bother in one
      individual and a severe form of bother in another. The aim of this study was to
      determine the factors contributing to the degree of bother due to a given degree
      of prolapse, to help with the clinical evaluation of patients and planning of
      preventive intervention trials and surgical treatment. METHODS: Consecutive
      patient records of 654 women who had attended a urogynecology unit between August
      2011 and December 2012 were reviewed. All patients underwent a standardized
      interview, clinical examination and four-dimensional translabial ultrasound scan.
      The degree of bother was evaluated using a visual analog scale. RESULTS: Six
      hundred and thirty-six women were included in the analysis, with ultrasound data
      available for cystocele, rectocele and enterocele descent and rectocele depth
      measurements and 442 for uterine descent. 313 women (49.2%) had subjective
      symptoms of female pelvic organ prolapse at a mean bother score of 6.0 +/- 2.6.
      Average bother score for the complete dataset was 3.0 +/- 3.5. Parity, vaginal
      delivery, levator avulsion, any significant clinical prolapse or prolapse seen on
      ultrasound were associated with prolapse bother and all clinical and ultrasound
      measures of pelvic organ descent remained significant or near significant on
      multivariate analysis. CONCLUSIONS: Quantification of prolapse bother using a
      visual analog scale is valid and repeatable and may represent a simple tool for
      use in clinical practice.

PMID- 24127312
TI  - Evolution of etching kinetics and directional transition of nanowires formed on
      pyramidal microtextures.
AB  - Two-scale roughened silicon (Si) textures are considered promising architectures
      for versatile applications because of their excellent self-cleaning, light
      trapping, and biosensing capacities. In this study, we explore the directional
      control of nanowires formed on pyramidal microtextures through a single-step
      metal-assisted chemical etching (MACE). The measured current density of Si
      dissolution at catalytic etching enables quantitative monitoring of the etching
      kinetics of nanowire formation. The preferential orientation of fabricated
      nanowires on {111}-plane pyramidal textures was found to positively correlate
      with the molar ratio of [AgNO3 ] to ([AgNO3 ]+[HF]), referred to as rho. A
      distinct transition from <100> to <111> axial directions at rho>=0.2 and
      rho=0.07, respectively, was revealed. The <111>-oriented nanowires on the
      pyramidal microtextures exhibited an excellent antireflection performance, with a
      reflectivity as low as 1.2% at 600 nm. The results of this study may aid the
      design for the development of high-performance Si-based optoelectronic devices.

PMID- 24127313
TI  - Helical self-assembly of optically active phthalocyanine derivatives: effect of
      Zn-O coordination bond on morphology and handedness of nanostructures.
AB  - Two optically active phthalocyanine derivatives with eight peripheral chiral (S)
      4'-(2-methylbutoxy)biphenyl moieties on the beta-position of the phthalocyanine
      ring are synthesized. The circular dichroism (CD) spectra show signals in the Q
      absorption region for both compounds 1 and 2 in chloroform solution, indicating
      the effective chiral-information transfer from the peripheral chiral (S)-4'-(2
      methylbutoxy)biphenyl side chains to the phthalocyanine chromophore at the
      molecular level. Their self-assembling properties are further investigated by
      using electronic absorption and Fourier transform infrared spectroscopy,
      transmission electronic microscopy, scanning electronic microscopy, X-ray
      diffraction, and X-ray photoelectron spectroscopy. Experimental results reveal
      the effect of the metal-coordination bond on molecular packing models in these
      nanostructures, which in turn results in the self-assembled nanostructures with
      different morphologies, from nanosheets for 1 to helical nanofibers for 2. In
      addition, good semiconducting properties of the nanostructures fabricated from
      phthalocyanine derivatives 1 and 2 are revealed by current-voltage measurements. 

PMID- 24127316
TI  - Heterozygote of PLCE1 rs2274223 increases susceptibility to human papillomavirus
      infection in patients with esophageal carcinoma among the Kazakh populations.
AB  - The involvement of human papillomavirus (HPV) in the carcinogenesis of esophageal
      squamous carcinoma remains undetermined. However, three genome-wide association
      studies of esophageal cancer have identified a shared susceptibility locus at
      10q23 (rs2274223: A5780G) in phospholipase C epsilon 1 (PLCE1). The current study
      aims to present a comprehensive and novel spectrum about the HPV genotype
      distribution of esophageal carcinoma in Kazakhs and assess its association with
      PLCE1 polymorphisms. The HPV genotypes in 183 patients with esophageal cancer and
      89 controls selected from the Kazakh population were evaluated using the HPV gene
      chip. The PLCE1 rs2274223 variant was genotyped in esophageal carcinoma patients
      by MALDI-ToF Mass Spectrometry. The presence of seven HPV genotypes in esophageal
      carcinoma tissues-including HPV 16, 18, 35, 52, 6, 11, 43-was significantly
      higher at 31.7% than those in controls at 9.0% (P < 0.001). Such presence was
      strongly associated with increased risk of esophageal carcinoma (OR 4.70; 95% CI
      2.13-10.36). Among all HPV genotypes detected, HPV16 was the most common genotype
      identified (29.0%, OR 4.13; 95% CI 1.87-9.13), which is significantly associated
      with well-differentiated esophageal carcinoma (P = 0.037). HPV-positive patients
      were generally younger than HPV-negative patients (70.1% vs. 29.3%, P = 0.013).
      PLCE1 rs2274223 genotypes AG and AG/GG were significantly associated with HPV
      positive patients with esophageal carcinoma (OR 2.05, 95% CI 1.03-4.08 and OR
      1.98, 95% CI 1.02-3.84, respectively). These findings suggest that heterozygote
      of PLCE1 rs2274223 increases susceptibility to HPV infection in patients with
      esophageal carcinoma among the Kazakh populations.

PMID- 24127317
TI  - Molecular phenotype of the foci in multifocal invasive breast carcinomas:
      intertumoral heterogeneity is related to shorter survival and may influence the
      choice of therapy.
AB  - BACKGROUND: Multiple synchronous, ipsilateral, invasive foci of breast carcinomas
      are frequent and are associated with a poorer prognosis. Few studies have
      investigated the prognostic and therapeutic implications of heterogeneity of such
      foci. METHODS: The authors reviewed the tumor type, grade, and size of all
      invasive foci in a series of 110 multifocal breast carcinomas documented on large
      format slides. Molecular phenotype was determined by immunohistochemistry in
      tissue microarray blocks using 3 classification systems. The survival of patients
      who had tumors with microscopic (tumor type and/or grade) heterogeneity and of
      those who had tumors with phenotypic heterogeneity was compared with the survival
      of patients who had multifocal homogeneous tumors using Kaplan-Meier curves. The
      hazard ratio of dying from breast cancer was also calculated. RESULTS:
      Intertumoral heterogeneity in tumor type and grade was detected in 16 of 110
      tumors (14.6%) and in 6 of 110 tumors (5.5%), respectively. The molecular
      phenotype of invasive tumor foci within the same breast differed in 10% to 12.7%
      of patients (11-14 of 110 tumors), depending on the classification system used.
      Patients who had phenotypically heterogeneous, multifocal cancers had a greater
      risk of dying from disease (HR=2.879; 95%CI=1.084-7.649; P = .034) and had
      significantly shorter survival (P = .016). Phenotypic differences were most
      common in patients who had tumors that were homogeneous in terms of tumor type
      (11 of 18 tumors) and histology grade (14 of 18 tumors). Phenotyping additional
      tumor foci had the potential to influence the therapeutic decisions in up to 8
      patients. CONCLUSIONS: Phenotyping more than 1 invasive focus of multifocal
      breast carcinomas only if the individual foci deviate microscopically appears to
      be insufficient, because phenotypic intertumoral heterogeneity may be observed in
      microscopically identical foci and has potential prognostic and therapeutic
      consequences.

PMID- 24127318
TI  - Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in
      mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.
AB  - Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell
      lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in
      MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1alpha) may regulate FoxP3
      expression; however, it is unknown whether HIF-1alpha is expressed in the CD4(+)
      T cells of MF patients and how it could affect the expression of FoxP3.
      Therefore, we evaluated the expression of HIF-1alpha and FoxP3 in CD4(+) T cells
      obtained from the skin lesions of MF patients. We found increased cell
      proliferation and an increase in CD4(+) T cells with an aberrant phenotype among
      early stage MF patients. HIF-1alpha was overexpressed in these CD4(+) T cells. In
      addition, we found a decrease in the percentage of FoxP3(+) cells both in the
      skin of MF patients, when compared with control skin samples, and with disease
      progression. In addition, a negative correlation was established between HIF
      1alpha and FoxP3 expression. Skin HIF-1alpha expression in MF patients correlated
      with the extent of the affected area and increased with the disease progression.
      Finally, we showed that ex vivo inhibition of HIF-1alpha degradation increases
      the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that
      overexpression of HIF-1alpha affects the levels of FoxP3 in MF patients, which
      could have relevant implications in terms of disease outcome. 

PMID- 24127319
TI  - Application of a Tenax model to assess bioavailability of polychlorinated
      biphenyls in field sediments.
AB  - Recent literature has shown that bioavailability-based techniques, such as Tenax
      extraction, can estimate sediment exposure to benthos. In a previous study by the
      authors, Tenax extraction was used to create and validate a literature-based
      Tenax model to predict oligochaete bioaccumulation of polychlorinated biphenyls
      (PCBs) from sediment; however, its ability to assess sediment remediation was
      unknown. The present study further tested the Tenax model by examining the
      impacts of remediation on surface sediment concentrations, Tenax extractable
      concentrations, and tissue concentrations of laboratory-exposed Lumbriculus
      variegatus. Tenax extractable concentration was an effective exposure metric to
      evaluate changes in Lumbriculus exposure preremediation and postremediation, with
      75% of the postremediation data corresponding to the Tenax model. At nondredged
      sites, bioaccumulation was better predicted by the Tenax model, with 86% of the
      data falling within the 95% confidence intervals, than at dredged sites, for
      which only 64% of the data fit the Tenax model. In both pre- and postdredge
      conditions, when the model failed, it was conservative, predicting higher PCB
      concentrations than observed in the oligochaetes, particularly for the postdredge
      data. The present study advances understanding of the applicability of the Tenax
      model for use when examining systems that may have undergone significant
      disturbances. The Tenax model provides a unique tool for quickly quantifying
      potential exposure to benthic organisms.

PMID- 24127322
TI  - General and selective C-3 alkylation of indoles with primary alcohols by a
      reusable Pt nanocluster catalyst.
AB  - The platinum rule: Heterogeneous, additive-free C-3 selective alkylation of
      indoles by aliphatic and aromatic alcohols proceeded under transfer hydrogenation
      conditions with the reusable Pt/theta-Al2 O3 catalyst (see scheme; TON=turnover
      number). 

PMID- 24127323
TI  - A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in
      Patients with Bone Marrow Failure.
AB  - Background: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal
      hematopoietic stem cell disorder, is characterized by chronic, uncontrolled
      complement activation leading to intravascular hemolysis and an inflammatory
      prothrombotic state. The EXPLORE study aimed to determine the prevalence of
      undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome
      (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH
      clone size on hemolysis. Methods: Patients, selected from medical office chart
      reviews, had blood samples collected for hematologic panel testing and for flow
      cytometry detection of PNH clones. Results: Granulocyte PNH clones >= 1% were
      detected in 199 of all 5398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of
      4401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher
      sensitivity analyses detected PNH clones >= 0.01% in 167 of 1746 patients from
      all groups (9.6%) and in 22 of 1225 MDS patients (1.8%), 116 of 294 AA patients
      (39.5%), and 4 of 54 other BMF patients (7.8%). Among patients with PNH clones >=
      1%, median clone size was smaller in patients with AA (5.1%) than in those with
      MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate
      dehydrogenase levels (a marker for intravascular hemolysis) >= 1.5 * upper limit
      of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%).
      Conclusions: These results confirm the presence of PNH clones in high-risk
      patient groups and suggest that screening of such patients may facilitate patient
      management and care. (c) 2013 Clinical Cytometry Society.

PMID- 24127324
TI  - Rectification in nanoscale devices based on an asymmetric five-coordinate
      iron(III) phenolate complex.

PMID- 24127325
TI  - Graphene analogues of inorganic layered materials.
AB  - The discovery of graphene has created a great sensation in chemistry, physics,
      materials science, and related areas. The unusual properties of graphene have
      aroused interest in other layered materials, such as molybdenum sulfide and boron
      nitride. In the last few years, single- as well as few-layer as well as
      chalcogenides and other inorganic materials have been prepared and characterized
      by a variety of methods. These materials possess interesting properties, and some
      have potential applications. This Review provides an up-to-date account of these
      emerging two-dimensional nanomaterials. Not only are the synthesis and
      characterization covered, but also important aspects such as spectroscopic and
      optical properties, magnetic and electrical properties, as well as applications.
      Salient features of the composites formed from the layered inorganic structures
      with graphene and polymers are presented along with a brief description of
      borocarbonitrides. 

PMID- 24127326
TI  - Fetal lung volume and quantification of liver herniation by magnetic resonance
      imaging in isolated congenital diaphragmatic hernia.
AB  - OBJECTIVE: To determine associations between fetal lung and liver herniation
      volumes measured by magnetic resonance imaging (MRI) and mortality/need for
      extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital
      diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI
      parameters with two-dimensional ultrasound lung measurements. METHODS: A
      retrospective review of medical records of all fetuses with isolated CDH
      evaluated between January 2004 and July 2012 was performed. The following MRI
      parameters were measured at 20-32 weeks: observed/expected total fetal lung
      volume (o/e-TLV), predicted pulmonary volume (PPV), percentage of liver herniated
      into the fetal thorax (%LH) and the liver/thoracic volume ratio (LiTR). These
      were compared with the ultrasound-determined lung-to-head ratio (LHR) and the
      observed/expected LHR (o/e-LHR) in the same cohort. The predictive value of MRI
      and ultrasound parameters for mortality and the need for ECMO was evaluated by
      univariate, multivariate and factor analysis and by receiver-operating
      characteristics curves. RESULTS: Eighty fetuses with isolated CDH were evaluated.
      Overall mortality was 18/80 (22.5%). Two newborns died a few hours after birth.
      ECMO was performed in 29/78 (37.2%) newborns, with a survival rate of 48.3%
      (14/29). The side of the diaphragmatic defect was not associated with mortality
      (P = 0.99) or the need for ECMO (P = 0.48). Good correlation was observed among
      o/e-TLV, PPV, LHR and o/e-LHR as well as between %LH and LiTR (r = 0.89; P <
      0.01); however, fetal lung measurements and measures of liver herniation were not
      correlated (all P > 0.05). All parameters were statistically associated with
      mortality or the need for ECMO. The best combination of measurements to predict
      mortality was o/e-TLV and %LH, with 83% accuracy. CONCLUSION: Mortality and the
      need for ECMO in neonates with isolated CDH can be best predicted using a
      combination of MRI o/e-TLV and %LH.

PMID- 24127327
TI  - Pilot study of etanercept in patients with refractory juvenile dermatomyositis.
AB  - OBJECTIVE: To evaluate the efficacy of etanercept in patients with juvenile
      dermatomyositis (DM) refractory to standard treatment. METHODS: Nine patients
      with juvenile DM prospectively received etanercept 0.4 mg/kg subcutaneous twice
      weekly concurrently with baseline medications for 12 weeks. Patients were
      reevaluated 12 weeks (week 24) after stopping etanercept. Outcome measures
      included a validated Disease Activity Score (DAS), serum muscle enzymes,
      Childhood Myositis Assessment Scale (CMAS), and nailfold capillaroscopy (NFC).
      RESULTS: Six patients completed all visits; 2 patients completed through week 12
      and 1 patient stopped after the fifth etanercept dose due to marked worsening of
      a rash. At week 12, 7 patients had a mild decrease in DAS and 1 patient noted
      worsening of the DAS. At week 24, 1 patient remained stable, 2 patients had
      worsening of the DAS, and 3 patients had improvement of the DAS (1 patient with
      inactive disease), including the patient who worsened while receiving etanercept.
      This patient and the patient who stopped (worsening rash) both had the tumor
      necrosis factor alpha (TNFalpha) 308A allele. There was a trend of worsening NFC
      at week 12, while at week 24 improvement of NFC was noted. There was no
      appreciable change in serum muscle enzymes or CMAS throughout the study.
      CONCLUSION: In this trial of patients with refractory juvenile DM, etanercept did
      not demonstrate appreciable improvement and some patients noted worsening of
      disease. Caution should be taken when recommending TNF receptor inhibitors to
      patients with active symptoms of juvenile DM, and close followup is warranted.
      Further investigation of the interaction of the TNFalpha-308A polymorphism and
      type I interferon is needed to define the mechanism of TNF blockade in juvenile
      DM.

PMID- 24127328
TI  - Coexistence of hepatitis B surface antigen and antibody to hepatitis B surface
      may increase the risk of hepatocellular carcinoma in chronic hepatitis B virus
      infection: a retrospective cohort study.
AB  - The simultaneous detection of hepatitis B surface antigen (HBsAg) and antibody to
      hepatitis B surface (anti-HBs) is unusual in chronic hepatitis B virus (HBV)
      infection, but may be related with more advanced liver diseases. This
      retrospective long-term cohort study was aimed to investigate whether coexistence
      of HBsAg and anti-HBs may increase the risk of hepatocellular carcinoma (HCC) in
      chronic HBV infection. A total of 1,042 non-HCC patients were recruited and
      followed up for a median 4.3 years (range 1.0-22 years). Univariate and
      multivariate analyses were performed to identify the risk factors for HCC
      development. The prevalence of coexistence of HBsAg and anti-HBs was 7.0%
      (73/1,042). In univariate analysis, the 5-, 10-, and 15-year cumulative
      incidences of HCC were significantly higher in coexistence group than in HBsAg
      only group (12.7%, 23.4%, 69.4% vs. 4.9%, 13%, 20.6%, respectively; P = 0.008).
      In multivariate analysis, coexistence of HBsAg and anti-HBs [Hazard ratio (HR),
      2.001; 95% confidence interval (CI), 1.023-3.912; P = 0.043] as well as male
      gender [HR, 1.898; 95% CI, 0.31-0.896; P = 0.018], age over 40 years [HR, 14.56;
      95% CI, 4.499-47.08; P = 0.0001], and cirrhosis [HR, 7.995; 95% CI, 4.756-13.439;
      P = 0.0001] was identified as the independent factor for HCC development. Also,
      the cumulative incidence of HCC increased in proportion to the number of the risk
      factors. In conclusion, coexistence of HBsAg and anti-HBs may increase
      independently the risk of HCC development in chronic HBV infection. Therefore,
      consideration of HCC development is required in patients with coexistence of
      HBsAg and anti-HBs.

PMID- 24127329
TI  - Are serotonergic system genes associated to smoking cessation therapy success in
      addition to CYP2A6?
AB  - Despite progress made in the treatment of tobacco dependence, currently available
      treatments are effective for only a fraction of smokers. The aim of this study
      was to evaluate the association between the effectiveness of treatment with
      nicotine or bupropion in heavy smokers (n=70), and 6 candidate polymorphisms in
      CYP2A6, 5-HTT and HTR2A genes. Analysis revealed a significant association
      between "favourable" genotype combination carriers (CYP2A6 "slow metabolizer" or
      5HTT L-allele or HTR2A-1438GG) and nicotine treatment outcome (OR=2.69, 95%
      CI=1.28-5.64). Genetic variations in CYP2A6 gene or genotypes associated with
      reduced synaptic serotonin activity may influence the success of smoking
      cessation treatment. 

PMID- 24127330
TI  - Interactions between mercury and phytoplankton: speciation, bioavailability, and
      internal handling.
AB  - The present review describes and discusses key interactions between mercury (Hg)
      and phytoplankton to highlight the role of phytoplankton in the biogeochemical
      cycle of Hg and to understand direct or indirect Hg effects on phytoplankton.
      Phytoplankton are exposed to various Hg species in surface waters. Through Hg
      uptake, phytoplankton affect the concentration, speciation, and fate of Hg in
      aquatic systems. The mechanisms by which phytoplankton take up Hg are still not
      well known, but several studies have suggested that both facilitated transport
      and passive diffusion could be involved. Once internalized, Hg will impact
      several physiological processes, including photosynthesis. To counteract these
      negative effects, phytoplankton have developed several detoxification strategies,
      such as the reduction of Hg to elemental Hg or its sequestration by intracellular
      ligands. Based on the toxicological studies performed so far in the laboratory,
      Hg is unlikely to be toxic to phytoplankton when they are exposed to
      environmentally relevant Hg concentrations. However, this statement should be
      taken with caution because questions remain as to which Hg species control Hg
      bioavailability and about Hg uptake mechanisms. Finally, phytoplankton are
      primary producers, and accumulated Hg will be transferred to higher consumers.
      Phytoplankton are a key component in aquatic systems, and their interactions with
      Hg need to be further studied to fully comprehend the biogeochemical cycle of Hg
      and the impact of this ubiquitous metal on ecosystems.

PMID- 24127331
TI  - An anthropomorphic design for a minimally invasive surgical system based on a
      survey of surgical technologies, techniques and training.
AB  - BACKGROUND: Over the past century, abdominal surgery has seen a rapid transition
      from open procedures to less invasive methods, such as robot-assisted minimally
      invasive surgery (MIS). This study aimed to investigate and discuss the needs of
      MIS in terms of instrumentation and to inform the design of a novel instrument.
      METHODS: A survey was conducted among surgeons regarding their opinions on
      surgical training, surgical systems, how satisfied they were with them and how
      easy they were to use. A concept for MIS robotic instrumentation was then
      developed and a series of focus groups with surgeons were run to discuss it. The
      initial prototype of the robotic instruments, herein demonstrated, comprises
      modular rigid links with soft joints actuated by shape memory alloy helix
      actuators; these instruments are controlled using a sensory hand exoskeleton.
      RESULTS: The results of the survey, as well as those of the focus groups, are
      presented here. A first prototype of the system was built and initial laboratory
      tests have been conducted in order to evaluate this approach. CONCLUSIONS: The
      analysed data from both the survey and the focus groups justify the chosen
      concept of an anthropomorphic MIS robotic system which imitates the natural
      motion of the hands.

PMID- 24127332
TI  - A miRNA signature associated with human metastatic medullary thyroid carcinoma.
AB  - MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that control gene
      expression by targeting mRNA and triggering either translational repression or
      RNA degradation. The objective of our study was to evaluate the involvement of
      miRNAs in human medullary thyroid carcinoma (MTC) and to identify the markers of
      metastatic cells and aggressive tumour behaviour. Using matched primary and
      metastatic tumour samples, we identified a subset of miRNAs aberrantly regulated
      in metastatic MTC. Deregulated miRNAs were confirmed by quantitative real-time
      PCR and validated by in situ hybridisation on a large independent set of primary
      and metastatic MTC samples. Our results uncovered ten miRNAs that were
      significantly expressed and deregulated in metastatic tumours: miR-10a, miR-200b/
      200c, miR-7 and miR-29c were down-regulated and miR-130a, miR-138, miR-193a-3p,
      miR-373 and miR-498 were up-regulated. Bioinformatic approaches revealed
      potential miRNA targets and signals involved in metastatic MTC pathways.
      Migration, proliferation and invasion assays were performed in cell lines treated
      with miR-200 antagomirs to ascertain a direct role for this miRNA in MTC
      tumourigenesis. We show that the members of miR-200 family regulate the
      expression of E-cadherin by directly targeting ZEB1 and ZEB2 mRNA and through the
      enhanced expression of tumour growth factor beta (TGFbeta)-2 and TGFbeta-1.
      Overall, the treated cells shifted to a mesenchymal phenotype, thereby acquiring
      an aggressive phenotype with increased motility and invasion. Our data identify a
      robust miRNA signature associated with metastatic MTC and distinct biological
      processes, e.g., TGFbeta signalling pathway, providing new potential insights
      into the mechanisms of MTC metastasis.

PMID- 24127333
TI  - A global analysis of multitrial data investigating quality of life and symptoms
      as prognostic factors for survival in different tumor sites.
AB  - BACKGROUND: The objective of this study was to examine the prognostic value of
      baseline health-related quality of life (HRQOL) for survival with regard to
      different cancer sites using 1 standardized and validated patient self-assessment
      tool. METHODS: In total, 11 different cancer sites pooled from 30 European
      Organization for Research and Treatment of Cancer (EORTC) randomized controlled
      trials were selected for this study. For each cancer site, univariate and
      multivariate Cox proportional hazards modeling was used to assess the prognostic
      value (P< .05) of 15 HRQOL parameters using the EORTC Core Quality of Life
      Questionnaire (QLQ-C30). Models were adjusted for age, sex, and World Health
      Organization performance status and were stratified by distant metastasis.
      RESULTS: In total, 7417 patients completed the EORTC QLQ-C30 before
      randomization. In brain cancer, cognitive functioning was predictive for
      survival; in breast cancer, physical functioning, emotional functioning, global
      health status, and nausea and vomiting were predictive for survival; in
      colorectal cancer, physical functioning, nausea and vomiting, pain, and appetite
      loss were predictive for survival; in esophageal cancer, physical functioning and
      social functioning were predictive for survival; in head and neck cancer,
      emotional functioning, nausea and vomiting, and dyspnea were predictive for
      survival; in lung cancer, physical functioning and pain were predictive for
      survival; in melanoma, physical functioning was predictive for survival; in
      ovarian cancer, nausea and vomiting were predictive for survival; in pancreatic
      cancer, global health status was predictive for survival; in prostate cancer,
      role functioning and appetite loss were predictive for survival; and, in testis
      cancer, role functioning was predictive for survival. CONCLUSIONS: The current
      results demonstrated that, for each cancer site, at least 1 HRQOL domain provided
      prognostic information that was additive over and above clinical and
      sociodemographic variables.

PMID- 24127335
TI  - Ring-closing metathesis reactions: interpretation of conversion-time data.
AB  - Conversion-time data were recorded for various ring-closing metathesis (RCM)
      reactions that lead to five- or six-membered cyclic olefins by using different
      precatalysts of the Hoveyda type. Slowly activated precatalysts were found to
      produce more RCM product than rapidly activated complexes, but this comes at the
      price of slower product formation. A kinetic model for the analysis of the
      conversion-time data was derived, which is based on the conversion of the
      precatalyst (Pcat) into the active species (Acat), with the rate constant k(act),
      followed by two parallel reactions: 1) the catalytic reaction, which utilizes
      Acat to convert reactants into products, with the rate k(cat), and 2) the
      conversion of Acat into the inactive species (Dcat), with the rate k(dec). The
      calculations employ two experimental parameters: the concentration of the
      substrate (c(S)) at a given time and the rate of substrate conversion (
      dc(S)/dt). This provides a direct measure of the concentration of Acat and
      enables the calculation of the pseudo-first-order rate constants k(act), k(cat),
      and k(dec) and of k(S) (for the RCM conversion of the respective substrate by
      Acat). Most of the RCM reactions studied with different precatalysts are
      characterized by fast k(cat) rates and by the k(dec) value being greater than the
      k(act) value, which leads to quasistationarity for Acat. The active species
      formed during the activation step was shown to be the same, regardless of the
      nature of different Pcats. The decomposition of Acat occurs along two parallel
      pathways, a unimolecular (or pseudo-first-order) reaction and a bimolecular
      reaction involving two ruthenium complexes. Electron-deficient precatalysts
      display higher rates of catalyst deactivation than their electron-rich relatives.
      Slowly initiating Pcats act as a reservoir, by generating small stationary
      concentrations of Acat. Based on this, it can be understood why the use of
      different precatalysts results in different substrate conversions in olefin
      metathesis reactions.

PMID- 24127334
TI  - Tact training versus bidirectional intraverbal training in teaching a foreign
      language.
AB  - The current study involved an evaluation of the emergence of untrained verbal
      relations as a function of 3 different foreign-language teaching strategies. Two
      Spanish-speaking adults received foreign-language (English) tact training and
      native-to-foreign and foreign-to-native intraverbal training. Tact training and
      native-to-foreign intraverbal training resulted in the emergence of a greater
      number of untrained responses, and may thus be more efficient than foreign-to
      native intraverbal training. 

PMID- 24127336
TI  - Laboratory findings in patients with avian-origin influenza A (H7N9) virus
      infections.
AB  - Reports describing the laboratory findings associated with human H7N9 infections
      are limited. In this study, the laboratory findings of 39 patients with confirmed
      H7N9 infection were analyzed retrospectively. Patients were enrolled following
      admission to The First Affiliated Hospital, College of Medicine, Zhejiang
      University, the primary hospital for the treatment of patients with H7N9
      infections in Zhejiang province in China between March and April in 2013.
      Hematological abnormalities included leukopenia, lymphopenia, thrombocytopenia
      with prolonged prothrombin time (PT) and activated partial thromboplastin time
      (APTT) as well as elevation of D-dimer levels. Biochemical abnormalities included
      elevated serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST),
      creatine kinase (CK), alanine aminotransferase (ALT) activities, and increased C
      reactive protein (CRP) concentration, as well as hyponatremia, hypokalemia,
      hypocalcemia, hypoproteinemia, and hypoalbuminemia. Arterial blood gas analysis
      revealed reduced arterial oxygen (PaO2) and carbon dioxide pressures (PaCO2). The
      data obtained in this study indicate that such abnormal laboratory features
      exhibited during the early stage of infection are common but not pathognomonic
      for the novel avian-origin influenza A strain H7N9; therefore, these features do
      not to allow the definitive differentiation of H7N9 infection from those of other
      viruses.

PMID- 24127337
TI  - Low-level laser therapy (810 nm) protects primary cortical neurons against
      excitotoxicity in vitro.
AB  - Excitotoxicity describes a pathogenic process whereby death of neurons releases
      large amounts of the excitatory neurotransmitter glutamate, which then proceeds
      to activate a set of glutamatergic receptors on neighboring neurons (glutamate, N
      methyl-D-aspartate (NMDA), and kainate), opening ion channels leading to an
      influx of calcium ions producing mitochondrial dysfunction and cell death.
      Excitotoxicity contributes to brain damage after stroke, traumatic brain injury,
      and neurodegenerative diseases, and is also involved in spinal cord injury. We
      tested whether low level laser (light) therapy (LLLT) at 810 nm could protect
      primary murine cultured cortical neurons against excitotoxicity in vitro produced
      by addition of glutamate, NMDA or kainate. Although the prevention of cell death
      was modest but significant, LLLT (3 J/cm(2) delivered at 25 mW/cm(2) over 2 min)
      gave highly significant benefits in increasing ATP, raising mitochondrial
      membrane potential, reducing intracellular calcium concentrations, reducing
      oxidative stress and reducing nitric oxide. The action of LLLT in abrogating
      excitotoxicity may play a role in explaining its beneficial effects in diverse
      central nervous system pathologies.

PMID- 24127339
TI  - Enhancement of chemical stability and crystallinity in porphyrin-containing
      covalent organic frameworks by intramolecular hydrogen bonds.
AB  - A strong bond: A strategy based on intramolecular hydrogen-binding interactions
      in 2D covalent organic frameworks (COFs) is shown to improve the crystallinity,
      porosity, and chemical stability of the material. The concept is validated by
      removing the hydrogen-bonding interaction in the methoxy analog which showed a
      lower stability and crystallinity. 

PMID- 24127338
TI  - Postprandial fatty acid specific changes in circulating oxylipins in lean and
      obese men after high-fat challenge tests.
AB  - SCOPE: Circulating oxylipins may affect peripheral tissues and are assumed to
      play an important role in endothelial function. They are esterified in
      triglyceride-rich lipoproteins that are increased after a high-fat (HF) meal,
      depending on BMI and fatty acid (FA) type. Yet, it is unclear which oxylipins
      appear in circulation after HF meals differing in FA composition. METHODS AND
      RESULTS: In a double-blind randomized crossover challenge study, we characterized
      the postprandial oxylipin response after different HF challenges in lean and
      obese men receiving HF milkshakes, either high in saturated FAs (SFA),
      monounsaturated FAs (MUFA), or omega 3 (n-3) polyunsaturated FAs (PUFA). Plasma
      oxylipin profiles were significantly altered at 2 and 4 h after shake consumption
      when compared to baseline. Eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) derived oxylipins increased after n-3 PUFA shake consumption. MUFA shake
      consumption increased levels of cytochrome P450 mediated oxylipins. SFA shake
      consumption led to strong increases in linoleic acid (LA) derived HODEs. No
      differences were observed between lean and obese individuals at baseline and
      after any shake consumption. CONCLUSION: We are the first demonstrating acute
      effects on circulating oxylipins after HF meal challenges. These changes were
      strongly influenced by different dietary FAs and may affect endothelial function.

PMID- 24127340
TI  - The dataset for protein-RNA binding affinity.
AB  - We have developed a non-redundant protein-RNA binding benchmark dataset derived
      from the available protein-RNA structures in the Protein Database Bank. It
      consists of 73 complexes with measured binding affinity. The experimental
      conditions (pH and temperature) for binding affinity measurements are also listed
      in our dataset. This binding affinity dataset can be used to compare and develop
      protein-RNA scoring functions. The predicted binding free energy of the 73
      complexes from three available scoring functions for protein-RNA docking has a
      low correlation with the binding Gibbs free energy calculated from Kd.

PMID- 24127341
TI  - Mechanisms of autocatalysis.
AB  - Self-replication is a fundamental concept. The idea of an entity that can
      repeatedly create more of itself has captured the imagination of many thinkers
      from von Neumann to Vonnegut. Beyond the sciences and science fiction,
      autocatalysis has found currency in economics and language theory, and has raised
      ethical fears memorably summed up by the "gray goo" trope. Autocatalysis is
      central to the propagation of life and intrinsic to many other biological
      processes. This includes the modern conception of evolution, which has radically
      altered humanity's image of itself. Organisms can be thought of as imperfect self
      replicators which produce closely-related species, allowing for selection and
      evolution. Hence, any consideration of self-replication raises one of the most
      profound questions of all: what is life? Minimal self-replicating systems have
      been studied with the aim of understanding the principles underlying living
      systems, allowing us to refine our concepts of biological fitness and chemical
      stability, self-organization and emergence, and ultimately to discover how
      chemistry may become biology. 

PMID- 24127342
TI  - Decline in hand bone mineral density indicates increased risk of erosive change
      in early rheumatoid arthritis.
AB  - OBJECTIVE: Despite better disease suppression with combination disease-modifying
      antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have
      progressive erosive disease. The objective of this study was to determine whether
      hand bone mineral density (BMD) loss in the first 6 months of treatment indicates
      increased risk of erosions at 12 months. METHODS: Patients with DMARD-naive early
      RA receiving treat-to-target therapy were studied (n = 106). Hand BMD was
      measured at baseline and 6 months by dual x-ray absorptiometry. Hand and feet
      radiographs were performed at baseline and 12 months and scored using the van der
      Heijde modification of the Sharp method. A K-means clustering algorithm was used
      to divide patients into 2 groups: the BMD loss group or the no loss group,
      according to their absolute change in BMD from baseline to 6 months. Multiple
      regression analysis (hurdle model) was performed to determine the risk factors
      for both erosive disease and erosion scores. RESULTS: Hand BMD loss at 6 months
      was associated with erosion scores at 12 months (P = 0.021). In a multiple
      regression analysis, hand BMD loss (P = 0.046) and older age at onset (>=50
      years; P = 0.014) were associated with erosive disease, whereas baseline erosion
      scores (P = 0.001) and anti-cyclic citrullinated peptide (P = 0.024) were
      correlated with erosion severity/progression. CONCLUSION: In RA patients
      receiving treat-to-target therapy, early hand BMD loss could identify patients
      who are at risk of developing erosive disease at 12 months, potentially allowing
      intensification of treatment to prevent erosive damage.

PMID- 24127343
TI  - [Magic bullet: transmediastinal gunshot wound].

PMID- 24127344
TI  - "Anatomy and imaging": 10 years of experience with an interdisciplinary teaching
      project in preclinical medical education - from an elective to a curricular
      course.
AB  - PURPOSE: Presentation of an interdisciplinary, interactive, tutor-based
      preclinical teaching project called "Anatomy and Imaging". MATERIALS AND METHODS:
      Experience report, analysis of evaluation results and selective literature
      review. RESULTS: From 2001 to 2012, 618 students took the basic course (4 periods
      per week throughout the semester) and 316 took the advanced course (2 periods per
      week). We reviewed 557 (return rate 90.1 %) and 292 (92.4 %) completed evaluation
      forms of the basic and the advanced course. Results showed overall high
      satisfaction with the courses (1.33 and 1.56, respectively, on a 5-point Likert
      scale). The recognizability of the relevance of the course content for medical
      training, the promotion of the interest in medicine and the quality of the
      student tutors were evaluated especially positively. CONCLUSION: The "Anatomy and
      Imaging" teaching project is a successful concept for integrating medical imaging
      into the preclinical stage of medical education. The course was offered as part
      of the curriculum in 2013 for the first time. "Anatomia in mortuis" and "Anatomia
      in vivo" are not regarded as rivaling entities in the delivery of knowledge, but
      as complementary methods.

PMID- 24127345
TI  - Percutaneous transhepatic and transsplenic portal vein access: embolization of
      the puncture tract using amplatzer vascular plugs.
AB  - PURPOSE: To report on first results of the embolization of transhepatic and
      transsplenic puncture tracts using an Amplatzer Vascular Plug (AVP) after
      percutaneous portal vein intervention. MATERIALS AND METHODS: Embolization of
      transhepatic and transsplenic puncture tracts with AVP was attempted in 5
      patients (3 females; age range: 3 - 71 years). Portal vein access was gained by a
      transhepatic (n = 4) or transsplenic (n = 1) approach, and stenosis (n = 2) or
      thrombosis (n = 3) of the portal vein was successfully treated by percutaneous
      stenting or thrombus aspiration and thrombolysis using 6 to 10 French sheaths.
      Due to the relatively large bore and/or short transparenchymal puncture tracts,
      it was considered favorable to use AVPs as an embolic agent. The medical records,
      the radiological reports and images of these 5 patients were retrospectively
      evaluated. RESULT: In three cases one AVP II (diameter, 4 mm), in one case one
      AVP IV (diameter, 4 mm) and in one case two AVPs II (diameter, 8 and 6 mm) were
      used for embolization of the puncture tract. In all five cases embolization was
      technically successful. There was no bleeding from the puncture tract. During a
      median follow-up of 14 months (range, 21 days to 21 months), one patient
      developed a focal liver abscess adjacent to the AVP which was successfully
      treated by antimicrobial and drainage therapy. There were no further embolization
      related complications. CONCLUSION: AVPs are suited to embolize large bore and/or
      short transhepatic and transsplenic puncture tracts effectively, safely, and
      precisely. Caution is required in patients with an increased risk for infectious
      complications. KEY POINTS: * Embolization of transhepatic and transsplenic
      puncture tracts with AVPs is feasible* Large and/or short puncture tracts can be
      effectively embolized with AVPs* The risk of infectious complications has to be
      considered Citation Format: * Dollinger M, Goessmann H, Mueller-Wille R et al.
      Percutaneous Transhepatic and Transsplenic Portal Vein Access: Embolization of
      the Puncture Tract Using Amplatzer Vascular Plugs. Fortschr Rontgenstr 2014; 186:
      142 - 150.

PMID- 24127346
TI  - Intravenous aflibercept in patients with platinum-resistant, advanced ovarian
      cancer: results of a randomized, double-blind, phase 2, parallel-arm study.
AB  - BACKGROUND: In this randomized phase 2 study, the authors assessed the efficacy
      and safety of intravenous aflibercept at 2 different doses (2 mg/kg or 4 mg/kg)
      in patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian
      tube cancer who developed disease progression after receiving topotecan and/or
      pegylated liposomal doxorubicin. METHODS: Patients were randomized to receive
      intravenous aflibercept at a dose of either 2 mg/kg or 4 mg/kg every 2 weeks
      until they developed disease progression or significant toxicity. The primary
      endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response
      rates (overall response rate [ORR] = complete responses plus partial responses)
      and to test the null hypothesis (ORR, >5%). Secondary endpoints included time to
      tumor progression, safety, progression-free survival/overall survival, drug
      pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort
      were planned based on a Simon 2-stage design, and, if those patients responded,
      then enrollment could extend to 200 patients. Tumor radiographic response was
      assessed by investigators and by an independent review committee. RESULTS: After
      the first 84 evaluable patients, 8 unconfirmed partial responders were noted
      (ORR, 10%) across both arms; the Independent Data Monitoring Committee
      recommended continuing blinded accrual. At study completion, 215 evaluable
      patients were accrued, including 1 responder of 106 patients (0.9%) in the 2
      mg/kg cohort and 5 responders of 109 patients (4.6%) in the 4-mg/kg cohort
      according to the independent review committee. The clinical benefit rate (ORR
      plus stable disease >6 months) was 12.3% and 11% in the 2-mg/kg and 4-mg/kg
      cohorts, respectively. Treatment-related grade 3 and 4 adverse events included
      hypertension (25.5% and 27.5% in the 2-mg/kg and 4-mg/kg cohorts, respectively),
      proteinuria (9.4% and 7.3%, respectively), and fatigue (5.7% and 3.7%,
      respectively). The gastrointestinal perforation rate was low (3 patients; 1.4%).
      CONCLUSIONS: Aflibercept at a dose of either 2 mg/kg or 4 mg/kg was generally
      well tolerated but did not meet the primary endpoint for response.

PMID- 24127347
TI  - Direct manipulation of tool-like masters for controlling a master-slave surgical
      robotic system.
AB  - BACKGROUND: Robotic-assisted minimally invasive surgery (MIS) can benefit both
      patients and surgeons. However, the learning curve for robotically assisted
      procedures can be long and the total system costs are high. Therefore, there is
      considerable interest in new methods and lower cost controllers for a surgical
      robotic system. METHODS: In this study, a knife-master and a forceps-master,
      shaped similarly to a surgical knife and forceps, were developed as input devices
      for control of a master-slave surgical robotic system. In addition, a safety
      strategy was developed to eliminate the master-slave orientation difference and
      stabilize the surgical system. RESULTS: Master-slave tracking experiments and a
      ring-and-bar experiment showed that the safety tracking strategy could ensure
      that the robot system moved stably without any tremor in the tracking motion.
      Subjects could manipulate the surgical tool to achieve the master-slave operation
      with less training compared to a mechanical master. CONCLUSIONS: Direct
      manipulation of the small, light and low-cost surgical tools to control a robotic
      system is a possible operating mode. Surgeons can operate the robotic system in
      their own familiar way, without long training. The main potential safety issues
      can be solved by the proposed safety control strategy.

PMID- 24127348
TI  - Comparison of nanorod-structured Li[Ni0.54 Co0.16 Mn0.30 ]O2 with conventional
      cathode materials for Li-ion batteries.
AB  - We successfully synthesized a safe, high-capacity cathode material specifically
      engineered for EV applications with a full concentration gradient (FCG) of Ni and
      Co ions at a fixed Mn content throughout the particles. The electrochemical and
      thermal properties of the FCG Li[Ni(0.54)Co(0.16)Mn(0.30)]O2 were evaluated and
      compared to those of conventional Li[Ni(0.5) Co(0.2) Mn(0.3)]O2 and
      Li[Ni(1/3)Co(1/3)Mn(1/3)]O2 materials. It was found that the FCG
      Li[Ni(0.54)Co(0.16)Mn(0.30)]O2 demonstrated a higher discharge capacity and a
      superior lithium intercalation stability compared to Li[Ni(0.5) Co(0.2)Mn(0.3)]O2
      and Li[Ni(1/3)Co(1/3)Mn(1/3)]O2 over all of the tested voltage ranges. The
      results of electrochemical impedance spectroscopy and transition-metal
      dissolution demonstrate that the microstructure of primary particle with rod
      shaped morphology plays an important role in reducing metal dissolution, which
      thereby decreases the charge transfer resistance as a result of stabilization of
      the host structure.

PMID- 24127349
TI  - Facile iron-mediated dispersant-free suspension polymerization of methyl
      methacrylate via reverse ATRP in water.
AB  - An iron-mediated reverse ATRP of methyl methacrylate (MMA) is successfully
      carried out in water in the absence of any dispersants, using a water-soluble
      2,2'-azobis(2-methylpropionamidine) dihydrochloride (V-50) as the initiator and
      the stabilizer, and using an oil-soluble N,N-butyldithiocarbamate ferrum (Fe(S2
      CN(C4 H9 )2 )3 ) as the catalyst without adding any additional ligands. Micron
      sized PMMA particles with UV light-sensitive -S2 CN(C4 H9 )2 end group are
      obtained, and monomer droplet nucleation and suspension polymerization mechanism
      are proposed. Polymerization results demonstrated typical "living"/controlled
      characteristics of ATRP: first-order polymerization kinetics, linear increase of
      molecular weights with monomer conversion and narrow molecular weight
      distributions for the resultant PMMA particles. NMR spectroscopy and chain
      extension experiments under UV light irradiation confirm the attachment and
      livingness of UV light-sensitive -S2 CN(C4 H9 )2 group in the chain end. 

PMID- 24127350
TI  - Controlling mechanical properties of cell-laden hydrogels by covalent
      incorporation of graphene oxide.
AB  - Graphene-based materials are useful reinforcing agents to modify the mechanical
      properties of hydrogels. Here, an approach is presented to covalently incorporate
      graphene oxide (GO) into hydrogels via radical copolymerization to enhance the
      dispersion and conjugation of GO sheets within the hydrogels. GO is chemically
      modified to present surface-grafted methacrylate groups (MeGO). In comparison to
      GO, higher concentrations of MeGO can be stably dispersed in a pre-gel solution
      containing methacrylated gelatin (GelMA) without aggregation or significant
      increase in viscosity. In addition, the resulting MeGO-GelMA hydrogels
      demonstrate a significant increase in fracture strength with increasing MeGO
      concentration. Interestingly, the rigidity of the hydrogels is not significantly
      affected by the covalently incorporated GO. Therefore, this approach can be used
      to enhance the structural integrity and resistance to fracture of the hydrogels
      without inadvertently affecting their rigidity, which is known to affect the
      behavior of encapsulated cells. The biocompatibility of MeGO-GelMA hydrogels is
      confirmed by measuring the viability and proliferation of the encapsulated
      fibroblasts. Overall, this study highlights the advantage of covalently
      incorporating GO into a hydrogel system, and improves the quality of cell-laden
      hydrogels. 

PMID- 24127351
TI  - Bringing the science of proteins into the realm of organic chemistry: total
      chemical synthesis of SEP (synthetic erythropoiesis protein).
AB  - Erythropoietin, commonly known as EPO, is a glycoprotein hormone that stimulates
      the production of red blood cells. Recombinant EPO has been described as
      "arguably the most successful drug spawned by the revolution in recombinant DNA
      technology". Recently, the EPO glycoprotein molecule has re-emerged as a major
      target of synthetic organic chemistry. In this article I will give an account of
      an important body of earlier work on the chemical synthesis of a designed EPO
      analogue that had full biological activity and improved pharmacokinetic
      properties. The design and synthesis of this "synthetic erythropoiesis protein"
      was ahead of its time, but has gained new relevance in recent months. Here I will
      document the story of one of the major accomplishments of synthetic chemistry in
      a more complete way than is possible in the primary literature, and put the work
      in its contemporaneous context. 

PMID- 24127352
TI  - Triblock polyphiles through click chemistry: self-assembled thermotropic cubic
      phases formed by micellar and monolayer vesicular aggregates.
AB  - Three series of triblock polyphiles consisting of a rigid 4-phenyl-1,2,3-triazole
      or 1,4-diphenyl-1,2,3-triazole core with three lipophilic and flexible alkoxyl
      chains at one end and a polar glycerol group at the opposite end were synthesized
      by copper-catalyzed azide-alkyne click reactions. Their mesophase behavior was
      studied by polarizing optical microscopy, differential scanning calorimetry, and
      XRD. Depending on alkyl chain length and core length, a transition from hexagonal
      columnar to Pm3n-type cubic phases was observed. In the cubic phases, the
      molecules are organized as spherical objects. Remarkably, compounds with a longer
      core unit have a higher tendency to form these cubic phases, and their stability
      is strongly enhanced over those of the compounds with a shorter core, despite
      longer cores having a smaller cone angle and therefore being expected to disfavor
      the formation of spherical objects. There is a large difference in the number of
      molecules involved in the spherical aggregates formed by compounds with long and
      short cores. Whereas the aggregates in the cubic phases of the compounds with
      short rod units are small and could be regarded as micellar, the long-core
      compounds form much larger aggregates which are regarded as a kind of monolayer
      vesicular aggregate.

PMID- 24127353
TI  - Association of thrombotic microangiopathy and intimal hyperplasia with bleeding
      post-renal biopsy in antiphospholipid antibody-positive patients.
AB  - OBJECTIVE: Renal biopsy remains the gold standard investigation for both
      diagnostic and prognostic purposes in the clinical management of lupus nephritis.
      However, it is not without potentially significant complications. The objectives
      of this study were to determine the rate of significant bleeding post-renal
      biopsy in patients with lupus nephritis and to identify risk factors associated
      with hemorrhagic complications. METHODS: Clinical data were retrospectively
      collected on 215 renal biopsies performed over a 13-year period (1999-2012).
      Patients were categorized into 3 groups: a diagnosis of systemic lupus
      erythematosus (SLE) alone, SLE with coexisting antiphospholipid syndrome (APS),
      or a diagnosis of SLE with either positive anticardiolipin antibodies and/or
      lupus anticoagulant (LAC) without clinical APS manifestations. RESULTS: Major
      bleeding complications were significantly more common in those with coexisting
      APS and/or antiphospholipid antibodies (aPL). LAC, presence of thrombotic
      microangiopathy (TMA) on renal biopsy, older age at the time of the biopsy (age
      >40 years), and elevated serum creatinine (>400 MUmoles/liter) were independent
      risk factors for increased risk of bleeding. TMA and severe fibrous intimal
      hyperplasia on renal biopsy were significantly more prevalent in those who
      developed severe bleeding complications. CONCLUSION: Based on these findings,
      lupus nephritis patients with coexisting APS, positive LAC, and histologic
      evidence of TMA and/or fibrous intimal hyperplasia are at increased risk of
      bleeding post-renal biopsy. aPL should be checked in all lupus nephritis patients
      before undergoing renal biopsy, as this subset of patients warrants particular
      caution pre- and postprocedure.

PMID- 24127354
TI  - Molecular docking cannot accurately predict drug off-target effects: implications
      for the role of voriconazole in the exacerbation of myasthenia gravis.

PMID- 24127355
TI  - Pocket infections of cardiac implantable electronic devices treated by negative
      pressure wound therapy.
AB  - AIMS: Managing an infection of the pocket of a cardiac implantable electronic
      device (CIED) is frequently challenging. The wound is often treated with a drain
      or wet-to-dry dressings that allow healing by secondary intention. Such treatment
      can prolong the hospital stay and can frequently result in a disfiguring scar.
      Negative pressure wound therapy (NPWT) has been frequently used to promote the
      healing of chronic or infected surgical wounds. Here we describe the first series
      of 28 patients in which NPWT was successfully used to treat CIED pocket
      infections. METHODS AND RESULTS: After removal of the CIED and debridement of the
      pocket, a negative pressure of 125 mmHg continuously applied to the wound through
      an occlusive dressing. Negative pressure wound therapy was continued for a median
      of 5 days (range 2-15 days) and drained an average of 260 mL sero-sanguineous
      fluid (range 35-970 mL). At the conclusion of NPWT, delayed primary closure of
      the pocket was performed with 1-0 prolene mattress sutures. The median length of
      stay after CIED extraction was 11.0 days (range 2-43 days). Virtually all
      infected pockets healed without complications and without evidence of recurrent
      infection over a median follow-up of 49 days (range 10-752 days). One patient
      developed a recurrent infection when NPWT was discontinued prematurely and a new
      device was implanted at the infected site. CONCLUSION: We conclude that NPWT is a
      safe and effective means to promote healing of infected pockets with a low
      incidence of recurrent infection and a satisfactory cosmetic result.

PMID- 24127356
TI  - Permanent porosity derived from the self-assembly of highly luminescent molecular
      zinc carbonate nanoclusters.

PMID- 24127357
TI  - Collaborative action around implementation in Collaborations for Leadership in
      Applied Health Research and Care: towards a programme theory.
AB  - OBJECTIVES: In theory, greater interaction between researchers and practitioners
      should result in increased potential for implementation. However, we know little
      about whether this is the case, or what mechanisms might operate to make it
      happen. This paper reports findings from a study that is identifying and tracking
      implementation mechanisms, processes, influences and impacts in real time, over
      time in the Collaborations for Leadership in Applied Health Research and Care
      (CLAHRCs). METHODS: This is a longitudinal, realist evaluation case study. The
      development of the conceptual framework and initial hypotheses involved
      literature reviewing and stakeholder consultation. Primary data were collected
      through interviews, observations and documents within three CLAHRCs, and analysed
      thematically against the framework and hypotheses. RESULTS: The first round of
      data collection shows that the mechanisms of collaborative action, relationship
      building, engagement, motivation, knowledge exchange and learning are important
      to the processes and outcomes of CLAHRCs' activity, including their capacity for
      implementation. These mechanisms operated in different contexts such as competing
      agendas, availability of resources and the CLAHRCs' brand. Contexts and
      mechanisms result in different impact, including the CLAHRCs' approach to
      implementation, quality of collaboration, commitment and ownership, and degree of
      sharing and managing knowledge. CONCLUSION: Emerging features of a middle range
      theory of implementation within collaboration include alignment in organizational
      structures and cognitive processes, history of partnerships, responsiveness and
      resilience in rapidly changing contexts. CLARHCs' potential to mobilize knowledge
      may be further realized by how they develop insights into their function as
      collaborative entities.

PMID- 24127358
TI  - From what we know to what we do: lessons learned from the translational CLAHRC
      initiative in England.
AB  - OBJECTIVES: There exists a translation gap between academic research and clinical
      practice in health care systems. One policy-driven initiative to address the
      translation gap in England are the Collaborations for Leadership in Applied
      Health Research and Care (CLAHRCs), funded by the National Institute of Health
      Research (NIHR). These aim to bring together NHS organizations and universities
      to accelerate the translation of evidence-based innovation into clinical
      practice. Our aim was to draw out lessons for policy-makers regarding the
      mobilization of such initiatives. METHODS: Qualitative semi-structured interviews
      with 174 participants across nine CLAHRCs plus in-depth case studies across four
      CLAHRCs. Those interviewed were staff who were central to the CLAHRCs including
      senior managers and directors, junior and senior academics, and health care
      practitioners. RESULTS: Social positions of the CLAHRC leaders, conceived as
      institutional entrepreneurs, together with the antecedent conditions for CLAHRC
      bids, had an impact on the vision for a CLAHRC. The process of envisioning
      encompassed diagnostic and prognostic framing. Within the envisioning process,
      the utilization of existing activities and established relationships in the
      CLAHRC bid influenced early mobilization. However, in some cases, it led to a
      translational 'lock in' towards established models regarding applied research.
      CONCLUSIONS: The CLAHRC experiment in England holds important lessons for policy
      makers regarding how to address the translation gap. First, policy makers need to
      consider whether they set out a defined template for translational initiatives or
      whether variation is encouraged. We might expect a degree of learning from pilot
      activities within a CLAHRC that allows for greater clarity in the design of
      subsequent translational initiatives. Second, policy makers and practitioners
      need to understand the importance of both antecedent conditions and the social
      position of senior members of a CLAHRC (institutional entrepreneurs) leading the
      development of a bid. Whilst established and well-known clinical academics are
      likely to be trusted to lead CLAHRCs, and the presence of pre-existing
      organizational relationships are important for mobilization, privileging these
      aspects may constrain more radical change.

PMID- 24127359
TI  - Urologists' referral attitude for sacral neuromodulation for treating refractory
      idiopathic overactive bladder syndrome: discrete choice experiment.
AB  - AIMS: To investigate urologists' referral attitude for sacral neuromodulation
      (SNM) for treating refractory idiopathic overactive bladder syndrome (OAB) and to
      quantify the weight they attribute to clinical parameters to refrain from SNM
      referral. METHODS: We set up a vignette study using a discrete-choice design. The
      questionnaires were distributed at two national urological meetings. RESULTS: One
      hundred eight urologists completed the questionnaire. Three parameters were
      significantly associated with the decision to refrain from referral: absolute
      contraindications for SNM (anatomical low bladder compliance, current urinary
      tract infection, progressive neurological disease, urinary tumors) had the
      strongest association (0.78, 95% CI 0.58 to 0.97; P < 0.001), followed by cardiac
      pacemaker (0.24, 95% CI 0.08 to 0.39; P = 0.003), and diabetes mellitus (0.19,
      95% CI 0.06 to 0.32; P = 0.006). On the other hand, urologists considered fecal
      incontinence as an important parameter for referral (-0.16, 95% CI -0.29 to 
      0.04; P = 0.011). Current medication with antimuscarinics and polyuria played no
      role in the decision. Results in a subgroup of 24 neuro-urologists/functional
      urologists were similar but non-critical parameters were not associated with the
      decision to refrain from SNM referral. CONCLUSIONS: Besides absolute
      contraindications, other non-critical parameters such as cardiac pacemaker or
      diabetes mellitus influence urologists' decision to refrain from referral for
      SNM. We believe that the use of decision tools will help urologists identifying
      patients benefiting from SNM and therefore we call for broad dissemination of
      such tools into clinical practice.

PMID- 24127360
TI  - Early and long-term effect of thoracic endovascular aortic repair for Stanford B
      aortic dissection.
AB  - BACKGROUND: Uncomplicated Stanford B acute aortic dissection (AAD) is generally
      treated with medical management; whereas complicated dissections require surgery
      or thoracic endovascular aortic repair (TEVAR). Studies have demonstrated that
      long-term outcomes with medical management are suboptimal. Therefore, we sought
      to investigate the early and long-term clinical efficacy of TEVAR for Stanford B
      AAD. MATERIALS AND METHODS: From March 2004 to January 2008, 63 consecutive
      patients were treated and retrospectively placed into either one of the two
      groups, the TEVAR group (n = 42) and the medicine group (n = 21). All TEVAR
      procedures were performed in the acute phase. The changes of true and false lumen
      diameter were monitored with computed tomography angiography examinations in the
      thoracic aorta at the level of the stented segment at long-term follow-up.
      RESULTS: As compared with the medicine group, the age at intervention in the
      TEVAR group was higher (p < 0.05), and they also had more patent false lumen in
      this group. Patients in the TEVAR group had significantly longer hospital stays
      than those in the medicine group (p < 0.01). The incidence of the early events
      was not significantly different between the two groups. The incidence of aortic
      related late events and late death were significantly higher in the medicine
      group than those in the TEVAR group. Log-rank tests demonstrated that patients
      treated with medical management had significantly more late adverse events than
      did those treated with TEVAR (p < 0.01). At 1-year follow-up, the true lumen
      diameter in the thoracic aorta at the level of the stented segment increased
      significantly after TEVAR, and the mean reduction of false lumen diameter was
      highly significant. The remodeling was stable at 3 and 5 years after TEVAR.
      CONCLUSION: Patients with Stanford B AAD treated with TEVAR experienced fewer
      late adverse events than those treated with medical management, TEVAR could be an
      effective treatment for Stanford B AAD.

PMID- 24127361
TI  - Remote Targets for Right Coronary Artery Bypass: Distal Trunk or Posterior
      Descending Artery Grafting.
AB  - BACKGROUND: Choosing a good anastomotic site is crucial during surgical
      revascularization of the right coronary artery (RCA) system. In many instances of
      distal and/or sequential main trunk disease, either the right posterior
      descending coronary artery (RPDA) or distal part of the right main coronary
      artery (DRCA) is preferred as the target vessel. In this article, the saphenous
      vein graft (SVG) patency is compared between these two main targets in the long
      term. MATERIALS AND METHODS: Postoperative control coronary angiograms were
      obtained and assessed from 452 patients undergoing conventional on-pump coronary
      artery bypass grafting with either a DRCA (n = 305) or a RPDA graft (n = 147)
      after an average postoperative period of 5.8 +/- 4.3 years (range: 2 months-20
      years; a total of 2,627 patient-years). RESULTS: The overall graft patency was
      60%. The 15-year patency rate was better for the DRCA grafts than that for the
      RPDA grafts (32 +/- 5% vs. 19 +/- 6%, respectively; p = 0.001), irrespective of
      target vessel caliber. Other factors adversely influencing the long-term graft
      patency were poor target vessel quality (p = 0.002) and hypercholesterolemia (p =
      0.01). On the other hand, target vessel diameter, diabetes mellitus,
      hypertension, chronic renal insufficiency, obesity, peripheral arterial disease,
      or SVG quality were not associated with poor long-term graft patency in these
      patients having distal-type RCA disease. CONCLUSIONS: In the presence of distal
      and/or sequential right coronary disease, DRCA may be the target vessel of choice
      for bypass grafting, rather than the RPDA, mainly for better long-term SVG
      patency rates in this location.

PMID- 24127362
TI  - Sternocostal dislocation following open correction of pectus excavatum-"stairway
      phenomenon": complication management by means of sternocostal locking titanium
      plate osteosynthesis.
AB  - INTRODUCTION: Some open surgical methods describe complete sternocostal
      dissection with subsequent resynthesis. Lack of consolidation with painful
      sternocostal instability and retrosternal dislocation of sternal rib tips are
      possible complications. MATERIALS AND METHODS: Seven patients with symptomatic
      unilateral sternocostal dislocation were included in this study. After diagnosis,
      confirmed by three-dimensional computed tomography (CT), patients underwent open
      surgery. All affected ribs were reset and fixed to the sternum with the aid of
      titanium implants. RESULTS: The patients had, on average, unilateral dislocation
      of 3.4 rib joints with 15.4 mm retrosternal dislocation, which was fixed with 2.3
      plates. A titanium splint was also employed. The recurrent nature of the problem
      made procedures very time-consuming (average operation time: 3 hours 25 minutes).
      One patient suffered strong intraoperative bleeding requiring transfusion of
      blood products and access enlargement. Follow-up examinations showed high patient
      satisfaction (grade of 1.7; rating scale 1-6). Remaining rib instabilities were
      observed just as infrequently as were material failures. The sternocostal rib
      splint in the costal cartilage became loose and was removed. One patient
      exhibited a pectoral muscle asymmetry. No other complications were observed.
      CONCLUSION: The term "stairway phenomenon" describes the dislocation of
      sternocostal joints. Observed after open pectus excavatum correction it can
      trigger substantial physical complaints. Thus, preserving those joints during
      pectus repair is strongly recommended. Locking titanium plates are a safe
      alternative to sternocostal suture fixation and is characterized by high patient
      satisfaction.

PMID- 24127363
TI  - Photocatalytic hydrogen production using models of the iron-iron hydrogenase
      active site dispersed in micellar solution.
AB  - Iron-thiolate complexes of the type [Fe2 (MU-bdt)(CO)6-x P(OMe3 )x ] (bdt=S2 C6
      H4 =benzenedithiolate, x<=2) are simplified models of iron-iron hydrogenase
      enzymes. Recently, we have shown that these water-insoluble organometallic
      complexes, when included into micelles formed by sodium dodecyl sulfate (SDS),
      are good catalysts for the electrochemical production of hydrogen in aqueous
      solutions at pH<6. We herein report that the all-CO derivative [Fe2 (MU-bdt)(CO)6
      ] (1), owing to its comparatively low reduction potential, is also a robust
      molecular catalyst for visible-light-driven production of H2 in aqueous SDS
      solutions at pH 10.5. Irradiation at lambda=455 nm of a system consisting of
      complex 1, Eosin Y as a sensitizer, and triethylamine as an electron donor
      produced up to 0.86 mL of H2 in 4.5 h, corresponding to a turnover number of 117
      mol of H2 per mol of catalyst. In the presence of a large excess of sensitizer,
      the production of H2 lasted for more than 30 h, stressing the relative stability
      of complex 1 under the photocatalytic conditions used herein. Thermodynamic
      considerations and UV/Vis spectroscopy experiments suggest that the catalytic
      cycle begins with the photo-driven reduction of complex 1. The reduced
      intermediate reacts with a proton source to yield iron hydride. Subsequent
      reduction and protonation steps produce H2 , regenerating the starting complex.
      As a result, the iron-thiolate complex 1 is a versatile proton reduction catalyst
      that can utilize either solar or electrical energy inputs, providing a starting
      point for the construction of noble metal-free molecular systems for renewable H2
      production.

PMID- 24127364
TI  - Quality of life in patients with K-RAS wild-type colorectal cancer: the CO.20
      phase 3 randomized trial.
AB  - BACKGROUND: The CO.20 trial randomized patients with K-RAS wild-type,
      chemotherapy-refractory, metastatic colorectal cancer to receive cetuximab (CET)
      plus brivanib alaninate (BRIV) or CET plus placebo (CET/placebo). METHODS:
      Quality of life (QoL) was assessed using the European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and at 2,
      4, 6, 8, 12, 16, and 24 weeks until disease progression. Predefined coprimary QoL
      endpoints were time to deterioration (first worsening from baseline of >= 10
      points) on the Physical Function (PF) and Global (GHS) scales. RESULTS: Of 750
      randomized patients, 721 (358 of whom received CET/BRIV) were assessable for QoL.
      QoL compliance and baseline PF and GHS scores did not differ by treatment arm.
      The median time to deterioration was 1.6 months versus 1.1 months for GHS (P
      =.02) and 5.6 months versus 1.7 months for PF (P <.0001) favoring CET/placebo.
      Secondary analysis favored CET/placebo for QOL response on the PF, Cognitive
      Function, Fatigue, Nausea, Appetite, and Diarrhea scales. A greater percentage of
      patients on the CET/BRIV arm had PF worsening at 6 weeks (31% vs 17%). Clinical
      adverse events of >= grade 3 were more common with CET/BRIV than with
      CET/placebo, including fatigue (25% vs 11%), hypertension, rash, diarrhea,
      abdominal pain, dehydration, and anorexia. CONCLUSIONS: Compared with
      CET/placebo, the combination of CET/BRIV worsened time to QoL deterioration for
      patients with K-RAS wild-type, chemotherapy-refractory, metastatic colorectal
      cancer on the PF and GHS scales of European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire C30. This result may be due to
      higher rates of fatigue and gastrointestinal adverse events.

PMID- 24127365
TI  - Micellar cathodes from self-assembled nitroxide-containing block copolymers in
      battery electrolytes.
AB  - This contribution describes the synthesis of block copolymers containing
      electrochemically active blocks, their micellization, and finally their use as
      micellar cathodes in a lithium battery. The self-assembly of the synthesized
      poly(styrene)-block-poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl methacrylate) (PS
      b-PTMA) diblock copolymers is realized in a typical battery electrolyte made of 1
      m lithium trifluoromethanesulfonate dissolved in a mixture of ethylene
      carbonate/diethyl carbonate/dimethyl carbonate(1:1:1, in volume). Dynamic light
      scattering and atomic force micro-scopy indicate the formation of well-defined
      spherical micelles with a PS core and a PTMA corona. The electrochemical
      properties of those micelles are further investigated. Cyclic voltammograms show
      a reversible redox reaction at 3.6 V (vs Li(+) /Li). The charge/discharge
      profiles indicate a flat and reversible plateau around 3.6 V (vs Li(+) /Li).
      Finally, the cycling performances of the micellar cathodes are demonstrated. Such
      self-assembled block copolymers open new opportunities for nanostructured organic
      radical batteries. 

PMID- 24127366
TI  - Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability.
AB  - AIMS: Mirabegron, the first beta3 -adrenoceptor agonist to enter clinical
      practice, has a different mechanism of action from antimuscarinic agents. This
      review presents data on the efficacy, safety, and tolerability of mirabegron in
      studies conducted to date. METHODS: All clinical data on mirabegron that are
      currently in the public domain are included, including some in-press manuscripts.
      RESULTS: In Phase III clinical trials in patients with overactive bladder (OAB),
      mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy
      in treating the symptoms of OAB, including micturition frequency, urgency
      incontinence, and urgency. Significant improvements in micturition frequency,
      urgency incontinence, and mean volume voided/micturition were seen as early as
      the first assessment (week 4) for mirabegron 50 and 100 mg, and were maintained
      throughout treatment. Responder analyses showed a significant improvement with
      mirabegron 50 and 100 mg in terms of dry rates, >=50% reduction in mean number of
      incontinence episodes/24 hr, and the proportion of patients with <=8
      micturitions/24 hr at final visit. The benefit of mirabegron 50 and 100 mg was
      also evident in patients >=65 years of age, and in both treatment-naive patients
      and those who previously discontinued antimuscarinic therapy. These data
      therefore demonstrate a clinically meaningful benefit with mirabegron in the
      objective endpoints of OAB. Assessment of measures of health-related quality of
      life and treatment satisfaction showed that patients perceived treatment with
      mirabegron as meaningful. In OAB clinical trials of up to 12 months mirabegron
      appeared to be well tolerated. The most common adverse events (AEs) observed with
      mirabegron in clinical trials of up to 12 months were hypertension,
      nasopharyngitis, and urinary tract infection. The incidence of dry mouth was
      similar to placebo, and was between three and fivefold less than for tolterodine
      extended release 4 mg. Since dry mouth is the most bothersome AE associated with
      antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron
      may be a valuable treatment option for these patients. CONCLUSIONS: In Phase III
      clinical trials, mirabegron at daily doses of 25, 50, and 100 mg demonstrated
      significant efficacy in treating symptoms of OAB and, at doses of 50 and 100 mg,
      demonstrated significant improvements versus placebo on key secondary endpoints,
      as early as the first assessment (week 4), and these were maintained throughout
      treatment. In OAB clinical trials of up to 12 months, mirabegron appeared to be
      well tolerated.

PMID- 24127367
TI  - A photoreducible copper(II)-tren complex of practical value: generation of a
      highly reactive click catalyst.
AB  - A detailed study on the photoreduction of the copper(II) precatalyst 1 to
      generate a highly reactive cuprous species for the copper(I)-catalyzed alkyne
      azide cycloaddition (CuAAC) click reaction is presented. For the photoactive
      catalyst described herein, the activation is driven by a photoinduced electron
      transfer (PET) process harnessing a benzophenone-like ketoprofenate chromophore
      as a photosensitizer, which is equally the counterion. The solvent is shown to
      play a major role in the Cu(II) to Cu(I) reduction process as the final electron
      source, and the influence of the solvent nature on the photoreduction efficiency
      has been studied. Particular attention was paid to the use of water as a
      potential solvent, aqueous media being particularly appealing for CuAAC
      processes. The ability to solubilize the copper-tren complexes in water through
      the formation of inclusion complexes with beta-CDs is demonstrated. Data is also
      provided on the fate of the copper(I)-tren catalytic species when reacting with
      O2, O2 being used to switch off the catalysis. These data show that partial
      oxidation of the secondary benzylamine groups of the ligand to benzylimines
      occurs. Preliminary results show that when prolonged irradiation times are
      employed a Cu(I) to Cu(0) over-reduction process takes place, leading to the
      formation of copper nanoparticles (NPs). Finally, the main objective of this work
      being the development of photoactivable catalysts of practical value for the
      CuAAC, the catalytic, photolatent, and recycling properties of 1 in water and
      organic solvents are reported.

PMID- 24127368
TI  - Synthesis of a novel fluorescent probe based on 7-nitrobenzo-2-oxa-1,3-diazole
      skeleton for the rapid determination of vitamin B12 in pharmaceuticals.
AB  - A new fluorescent probe, 4-N,N-di(2-hydroxyethyl)imino-7-nitrobenzo-2-oxa-1,3
      diazole (HINBD) was synthesized in a single step with reasonably good yield. The
      water-soluble HINBD emits strongly in the visible region (lambdaex  = 479 nm,
      lambdaem  = 545 nm) and is stable over a wide range of pH values. It was found
      that vitamin B12 (VB12 ) had the ability to quench the fluorescence of HINBD, and
      the quenched fluorescence intensity was proportional to the concentration of VB12
      . A method for VB12 determination based on the quenching fluorescence of HINBD
      was thus established. Interference effects of various substances, including
      sugars, vitamins, amino acids, inorganic cations and some organic substances have
      been studied. Under optimal conditions, the linear range is 0.0-2.4 * 10(-5) 
      mol/L. The determination limit is 8.3 * 10(-8)  mol/L. The method was applied to
      measure VB12 in pharmaceutical preparations with satisfactory results.

PMID- 24127369
TI  - Canine olfactory detection of malignant melanoma.
AB  - Our patient is a 75-year-old man who presented after his pet dog licked
      persistently at an asymptomatic lesion behind his right ear. Examination revealed
      a nodular lesion in the postauricular sulcus. Histology confirmed malignant
      melanoma, which was subsequently excised. Canine olfactory detection of human
      malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to
      explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate
      and skin cancers. Further research in this area may facilitate the development of
      a highly accurate aid to diagnosis for many malignancies, including melanoma. 

PMID- 24127371
TI  - Single extremely large loose body in olecranon fossa in a young patient.

PMID- 24127370
TI  - Febrile ulceronecrotic Mucha-Habermann disease.
AB  - The Mucha-Habermann disease is an inflammatory disease of the skin and is a
      variant of pityriasis lichenoides et varioliformis acuta. We describe the case of
      a 64-years-old woman who was admitted for erysipelas of the face. Despite
      treatment, evolution was marked by the appearance of a necrotising ulcerative
      area in the centre of the erysipelas associated with local oedema and headache. A
      skin biopsy revealed a pityriasis lichenoides et varioliformis acuta.
      Corticosteroids led to a rapid stabilisation of lesions, and after 6 months the
      patient shows only a small area of frontal hypopigmentation. The aetiology
      remains uncertain. There is no established standard treatment. We would like to
      draw attention of the medical and surgical specialists to this rare disease. The
      diagnosis should be considered in a necrotic lesion associated with rapid
      expansion of systemic and peripheral cutaneous signs. Diagnosis must be
      considered to avoid unnecessary debridement and extensive scars. 

PMID- 24127372
TI  - Recanalization of acute carotid stent occlusion using Penumbra 4Max aspiration
      catheter: technical report and review of rescue strategies for acute carotid
      stent occlusion.
AB  - Carotid artery stenting (CAS) has become a widely used treatment for carotid
      artery stenosis, especially in high-risk patients. Acute in-stent and distal
      protection device occlusion are potentially catastrophic complications of this
      procedure. Previously described rescue strategies have included administration of
      antiplatelet agents (eg, abciximab) with/without thrombolytics and removal of the
      filter. Here we describe the successful resolution of in-stent occlusion by
      mechanical thrombolysis using the Penumbra 4Max aspiration catheter. Distal flow
      was subsequently restored with minimal residual stenosis. The patient did not
      suffer any consequent neurological deficits. The different strategies that could
      be used in this critical situation are reviewed. 

PMID- 24127373
TI  - An unusually high troponin I result in association with Legionella infection.
AB  - A 77-year-old man presented himself with shortness of breath that was initially
      felt to be due to an acute coronary event, largely due to a very elevated
      troponin I result and his medical history. He subsequently showed evidence to
      suggest a significant pneumonia. The most likely candidate organism responsible,
      from the history and test results, appeared to be Legionella. We present the case
      for a spuriously and extremely elevated troponin I result, being at least in part
      due the production of heterophil antibodies by Legionella. 

PMID- 24127374
TI  - Role of serial MRI assessment in the management of an abdominal pregnancy.
AB  - A 33-year-old woman was admitted to the hospital with an abdominal pregnancy at a
      gestational age of 20 weeks. An initial MRI mapping of fetal location and
      placental vascular invasion was obtained. The patient refused surgical
      intervention until fetal survival would be possible. Serial MRIs were essential
      in timing delivery and avoiding an emergency surgical situation. The baby was
      delivered at 24 weeks with the assistance of a multidisciplinary surgical team.
      The mother as well as the baby survived. This case report highlights the role of
      serial MRI evaluations in the diagnosis and expectant management of an abdominal
      pregnancy. It also highlights the importance of interdisciplinary communication
      for a successful outcome. 

PMID- 24127375
TI  - Shortness of breath, fever and abdominal pain in a 21-year-old student.
AB  - A 21-year-old patient presented with a 3-day history of shortness of breath,
      productive cough, fatigue, fevers and night sweats, associated with right upper
      quadrant pain. He had an appendicectomy 3 months previously. The CT images showed
      a right subphrenic collection, which was indenting the right lobe of the liver,
      with an appendicolith in the middle. He underwent laparoscopic surgery where the
      abscess was drained and the appendicolith was retrieved. The patient had an
      uncomplicated postoperative period and was discharged soon afterwards.
      Complications from spilled appendicoliths have been reported previously. Retained
      appendicoliths and gallstones can act as niduses for infection, and thus cause
      symptoms at a later stage. Surgical notes should include the findings of
      appendicoliths, and in the event where retrieval is not possible, a clear record
      of this must be made, and the patient along with the general practitioner need to
      be informed. 

PMID- 24127376
TI  - Adrenocortical carcinoma with tumour thrombus extension to right atrium: a rare
      finding in uncommon tumour.

PMID- 24127378
TI  - Beau's lines in postpartum period and hyperparathyroidism.

PMID- 24127377
TI  - Inhaled beta-agonist therapy and respiratory muscle fatigue as under-recognised
      causes of lactic acidosis.
AB  - A 49-year-old man with chronic obstructive pulmonary disease (COPD) presented
      with significant tachypnoea, fevers, productive cough and increased work of
      breathing for the previous 4 days. Laboratory data showed elevated lactate of 3.2
      mEq/L. Continuous inhaled ipratropium and albuterol nebuliser treatments were
      administered. Lactate levels increased to 5.5 and 3.9 mEq/L, at 6 and 12 h,
      respectively. No infectious source was found and the lactic acidosis cleared as
      the patient improved. The lactic acidosis was determined to be secondary to
      respiratory muscle fatigue and inhaled beta-agonist therapy, two under-recognised
      causes of lactic acidosis in patients presenting with respiratory distress.
      Lactic acidosis is commonly used as a clinical marker for sepsis and shock, but
      in the absence of tissue hypoperfusion and severe hypoxia, alternative
      aetiologies for elevated levels should be sought to avoid unnecessary and
      potentially harmful medical interventions. 

PMID- 24127379
TI  - 3-Methyl-4-oxa-5-azahomoadamantane: alkoxyamine-type organocatalyst for alcohol
      oxidation.

PMID- 24127380
TI  - Interval sampling methods and measurement error: a computer simulation.
AB  - A simulation study was conducted to provide a more thorough account of
      measurement error associated with interval sampling methods. A computer program
      simulated the application of momentary time sampling, partial-interval recording,
      and whole-interval recording methods on target events randomly distributed across
      an observation period. The simulation yielded measures of error for multiple
      combinations of observation period, interval duration, event duration, and
      cumulative event duration. The simulations were conducted up to 100 times to
      yield measures of error variability. Although the present simulation confirmed
      some previously reported characteristics of interval sampling methods, it also
      revealed many new findings that pertain to each method's inherent strengths and
      weaknesses. The analysis and resulting error tables can help guide the selection
      of the most appropriate sampling method for observation-based behavioral
      assessments. 

PMID- 24127381
TI  - Non-invasive chromosome test raises new questions in prenatal diagnosis about the
      significance of ultrasound and questions about new screening strategies.

PMID- 24127382
TI  - [DEGUM guidelines for amniocentesis and chorionic villus sampling].

PMID- 24127383
TI  - Tackling obesity: the challenge of obesity management for practice nurses in
      primary care.
AB  - BACKGROUND: Nurses in primary care, who see a large proportion of the population,
      are well placed to discuss weight with patients and offer management advice.
      Interventions to promote weight loss have shown that there are effective ways of
      making small changes for patients. OBJECTIVES: To use qualitative semi-structured
      interviews to explore how practice nurses manage obesity within primary care and
      to identify good practice and explore barriers to achieving effective management.
      METHODS: Eighteen semi-structured interviews were conducted with practice nurses
      within two local health board areas in South Wales. Interviews were audio
      recorded, transcribed and analysed qualitatively using a thematic approach.
      RESULTS: Nurses described two roles. One role was providing obesity management to
      patients who had co-morbid conditions and were seen regularly in chronic disease
      clinics. All nurses perceived that these patients needed their weight addressing
      routinely. The other role was to broach the subject with overweight but healthy
      patients. Nurses were of divided opinion whether to address obesity with these
      patients and what primary care had to offer. Weight management advice, when
      given, lacked consistency of approach. CONCLUSIONS: Broaching the subject of
      weight opportunistically with healthy but overweight patients may require a
      deeper appreciation of their motivations for change and discussion beyond future
      health risks. These patients also need clearer follow up to monitor their
      progress with weight loss. All overweight patients also need clearer guidance
      tailored to their own particular circumstances as to how to lose weight. For
      patients being counselled about their weight, interventions that promote
      consistency of advice are advocated to improve care.

PMID- 24127384
TI  - Complete Bordetella avium, Bordetella hinzii and Bordetella trematum lipid A
      structures and genomic sequence analyses of the loci involved in their
      modifications.
AB  - Endotoxin is recognized as one of the virulence factors of the Bordetella avium
      bird pathogen, and characterization of its structure and corresponding genomic
      features are important for an understanding of its role in pathogenicity and for
      an improved general knowledge of Bordetella spp virulence factors. The structure
      of the biologically active part of B. avium LPS, lipid A, is described and
      compared to those of another bird pathogen, opportunistic in humans, Bordetella
      hinzii, and to that of Bordetella trematum, a human pathogen. Sequence analyses
      showed that the three strains have homologues of acyl-chain modifying enzymes
      PagL, PagP and LpxO, of the 1-phosphatase LpxE, in addition to LgmA, LgmB and
      LgmC, which are required for the glucosamine modification. MALDI mass
      spectrometry identified a high amount of glucosamine substituting the phosphate
      groups of B. avium lipid A; this modification was absent from B. hinzii and B.
      trematum. The acylation patterns of the three lipid As were similar, but they
      differed from those of Bordetella pertussis and Bordetella parapertussis. They
      were also found to be close to the lipid A structure of Bordetella
      bronchiseptica, a mammalian pathogen, only differing from the latter by the
      degree of hydroxylation of the branched fatty acid. 

PMID- 24127385
TI  - Inflammatory changes of the lumbar spine in children and adolescents with
      enthesitis-related arthritis: magnetic resonance imaging findings.
AB  - OBJECTIVE: To describe and profile abnormalities of the lumbar spine in a cohort
      of patients with enthesitis-related arthritis (ERA) as compared to a control
      group of adolescents with mechanical back pain. METHODS: We performed a
      retrospective review of magnetic resonance imaging (MRI) lumbar spine scans of 79
      patients (58 cases, 21 controls). The study was covered by institutional review
      board approval and informed consent was obtained for review of all clinical
      investigations. Images were reviewed by an expert MRI reader who was blinded to
      clinical details. The presence or absence of morphologic features of enthesitis,
      apophyseal joint synovitis, and inflammation of posterior elements was assessed
      at each lumbar vertebral level. The apophyseal joint inflammation was graded from
      0 to 3 using a grading system that was adapted from one used in adults with
      inflammatory facet osteoarthropathy. STATA software was used for data analysis.
      RESULTS: One or more abnormalities of the lumbar spine were found in 39 (67%) of
      58 cases and sacroiliitis was present in 45 (78%) of the cases. Apophyseal joint
      synovitis was seen in 22 (38%) cases and in 1 (5%) control patient. This
      difference was highly significant (P = 0.004). Inflammatory changes in the
      interspinous ligaments were seen in a higher percentage of cases than controls
      and this observation was of statistical significance (P = 0.04). CONCLUSION:
      Statistically significant inflammation of the lumbar apophyseal joints and
      interspinous ligaments was seen in our cohort of ERA patients, most of whom have
      concurrent sacroiliitis. This could be contributing to back pain in these
      patients.

PMID- 24127386
TI  - Reduced graphene oxide/InGaZn mixed oxide nanocomposite photocatalysts for
      hydrogen production.
AB  - A series of reduced graphene oxide and indium-gallium-zinc mixed oxide (RGO/IGZ)
      nanocomposites were successfully synthesised by a simple one-step hydrothermal
      method. The as-synthesised nanocomposites were characterised by crystallographic,
      microscopic, and spectroscopic methods to explore the robust photocatalytic
      activity of the prepared materials. XRD patterns confirmed the formation of
      highly pure, single-phase, hexagonal In2 Ga2 ZnO7 with no impurity-related peaks.
      All the photocatalysts absorbed visible light as observed from the diffuse
      reflectance UV/Vis spectra. The electron-hole recombination is effectively
      minimised by the formation of an RGO/metal oxide nanocomposite, which was
      successfully derived from a photoluminescence (PL) study and photoelectrochemical
      measurements. The decoration of IGZ nanocrystals onto reduced graphene sheets
      leads to significant quenching of its luminescent intensity, dramatically
      improved photocurrent generation (33 times more than neat IGZ) and significantly
      enhanced photostability. The high photocatalytic activity for H2 production is
      explained by the strong interaction between the IGZ nanocrystals with RGO sheets,
      low PL intensity, high photocurrent and large surface area. 

PMID- 24127387
TI  - Effects of sales promotions, weight status, and impulsivity on purchases in a
      supermarket.
AB  - OBJECTIVE: Several environmental factors contribute to increased food consumption
      and play a role in the prevalence of obesity, like portion size, accessibility
      and relative price of high caloric foods, food commercials, and sales promotions.
      However, not everyone seems equally sensitive to these environmental cues and
      both obesity and impulsivity appears to play a role. METHODS: In this study, food
      purchases in an internet supermarket are tested in 118 participants, with or
      without sales promotions for snack foods. Both weight status and response
      inhibition, an index of impulsivity, are measured. RESULTS: Participants with
      less inhibitory control purchased in total more calories from the internet
      supermarket then participants with more inhibitory control. In addition, sales
      promotion, weight status, and inhibitory control appeared to interact in their
      effect on snack food purchases: participants with less inhibitory control and
      overweight bought more calories of snacks in the sales promotions condition, but
      not in the control condition. For the other participants, with normal weight
      and/or high inhibitory control, sales promotions had no effect on their purchases
      of calories of snacks. CONCLUSIONS: It seems that especially the combination of
      low inhibitory control and overweight makes participants vulnerable for
      environmental cues.

PMID- 24127388
TI  - Is fibromyalgia diagnosed with new criteria considerably different from
      fibromyalgia diagnosed with old criteria? Comment on the article by Wolfe et al.

PMID- 24127389
TI  - Let there be light: photo-cross-linked block copolymer nanoparticles.
AB  - Polymeric nanoparticles are prepared by selectively cross-linking a photo
      sensitive dimethylmaleimide-containing block of a diblock copolymer via UV
      irradiation. A well-defined photo-cross-linkable block copolymer is prepared via
      reversible addition-fragmentation chain transfer (RAFT) polymerization of a
      dimethylmaleimide-functional acrylamido monomer containing photoreactive pendant
      groups with a poly(N,N-dimethylacrylamide) (PDMA) macro-chain transfer agent. The
      resulting amphiphilic block copolymers form micelles in water with a hydrophilic
      PDMA shell and a hydrophobic photo-cross-linkable dimethylmaleimide-containing
      core. UV irradiation results in photodimerization of the dimethylmaleimide groups
      within the micelle cores to yield core-cross-linked aggregates. Alternatively, UV
      irradiation of homogeneous solutions of the block copolymer in a non-selective
      solvent leads to in situ nanoparticle formation. 

PMID- 24127390
TI  - XeF(2) /fluoride acceptors as versatile one-electron oxidants.
AB  - No phlogiston but xenon is released when XeF2 /F(-) acceptors act as new one
      electron oxidants. F(-) acceptors are Lewis acids BF3 , B(C6 F5 )3 , and
      Al{OC(CF3 )3 }3 , and silyl derivatives TfOSiMe3 , Tf2 NSiMe3 , Me3 Si(+)  B(C6
      F5 )4 (-) , and Me3 Si(+)  CHB11 Cl11 (-) . The anions BF4 (-) , TfO(-) , Tf2 N(
      ) , FB(C6 F5 )3 (-) , FAl{OC(CF3 )3 }3 (-) , B(C6 F5 )4 (-) , or CHB11 Cl11 (-)
      can be introduced into oxidation products of R2 E2 (E=S, Se, Te), [FeCp2 ],
      [(FeCpS)4 ], tetrathiafulvalene, thianthrene, and (2,4-Br2 C6 H3 )3 N. 

PMID- 24127392
TI  - Cholinesterase inhibitors and Pisa syndrome: a pharmacovigilance study.
AB  - STUDY OBJECTIVES: Case reports suggest a relationship between cholinesterase
      inhibitors (ChEIs) and Pisa syndrome (PS), also known as pleurothotonus, a form
      of dystonia, but this relationship has not been systematically examined. Our
      objective was to estimate the adjusted reporting ratios of PS with donepezil,
      rivastigmine, and galantamine in the United States Food and Drug Administration
      (FDA) Adverse Event Reporting System (FAERS) database. DESIGN: Retrospective
      analysis of adverse event reports in the FAERS database. PATIENTS: Patients with
      drug-related adverse events in the FAERS database. MEASUREMENTS AND MAIN RESULTS:
      The Gamma Poisson Shrinker algorithm was used to estimate the empirical Bayes
      geometric mean (EBGM) along with the lower and upper 90% confidence interval (CI)
      limits (EB05 and EB95, respectively), as measures of the adjusted reporting ratio
      of PS in patients taking ChEIs. EB05 > 2.0 was used as the cutoff for
      significance for the signals. The EBGM (EB05) was 37.9 (30) for all ChEIs, 25.6
      (17.6) for donepezil, 76.4 (50.3) for galantamine, and 33.7 (21.2) for
      rivastigmine. All adverse event signals were strongly significant based on the a
      priori set EB05 cutoff. The female:male ratio in the reported cases was 2:1. No
      significant signals were found between ChEIs and other dystonias. About half of
      the ChEI users were also taking concomitant antipsychotics. CONCLUSION: Although
      FAERS data cannot establish causality due to reporting biases, our findings
      support a potential dopaminergic-cholinergic imbalance as an underlying mechanism
      for PS and may help increase clinician awareness, early identification, and
      treatment of ChEI-related dystonias.

PMID- 24127391
TI  - Cigarette smoking is associated with an increased risk of biochemical disease
      recurrence, metastasis, castration-resistant prostate cancer, and mortality after
      radical prostatectomy: results from the SEARCH database.
AB  - BACKGROUND: The current study was conducted to analyze the association between
      cigarette smoking and metastasis (the primary outcome) as well as time to
      biochemical disease recurrence (BCR), metastasis, castration-resistant prostate
      cancer (CRPC), and prostate cancer-specific and overall mortality (secondary
      outcomes) after radical prostatectomy among men from the Shared Equal Access
      Regional Cancer Hospital cohort. METHODS: A retrospective analysis was performed
      of 1450 subjects for whom smoking status was available from preoperative notes.
      Analysis of baseline characteristics by smoking status was performed using the
      chi-square and rank sum tests. The association between smoking status and time to
      the event was analyzed using Kaplan-Meier plots, the log-rank test, and Cox and
      competing risk models. RESULTS: A total of 549 men (33%) men were active smokers
      and 1121 (67%) were nonsmokers at the time of surgery. Current smokers were
      younger and had a lower body mass index, higher prostate-specific antigen level,
      and more extracapsular extension and seminal vesicle invasion (all P<.05). A
      total of 509 patients, 26 patients, 30 patients, 18 patients, and 217 patients,
      respectively, experienced BCR, metastasis, CRPC, prostate cancer-related death,
      and any-cause death over a median follow-up of 62 months, 75 months, 61 months,
      78 months, and 78 months, respectively. After adjusting for preoperative
      features, active smoking was found to be associated with an increased risk of BCR
      (hazards ratio [HR], 1.25; P=.024), metastasis (HR, 2.64; P=.026), CRPC (HR,
      2.62; P=.021), and overall mortality (HR, 2.14; P<.001). Similar results were
      noted after further adjustment for postoperative features, with the exception of
      BCR (HR, 1.10; P=.335), metastasis (HR, 2.51; P=.044), CRPC (HR, 2.67; P=.015),
      and death (HR, 2.03; P<.001). CONCLUSIONS: Among patients undergoing radical
      prostatectomy, cigarette smoking was associated with an increased risk of
      metastasis. In addition, smoking was associated with a higher risk of BCR, CRPC,
      and overall mortality. If confirmed, these data suggest that smoking is a
      modifiable risk factor in patients with aggressive prostate cancer.

PMID- 24127393
TI  - Palladium-catalyzed synthesis of benzofurans and coumarins from phenols and
      olefins.

PMID- 24127394
TI  - Postoperative monitoring of local and free flaps with contrast-enhanced
      ultrasound (CEUS)--analysis of 112 patients.
AB  - PURPOSE: Tissue defects are a common problem in trauma surgery and oncology. Flap
      transplantation is often the only therapy to cover such defects. Several
      monitoring systems are currently available but none has made it to the clinical
      routine. The aim of this study was to assess perfusion disturbances of local and
      free flaps using contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: 112
      patients were examined during the first 72 hours after operation. CEUS was
      performed by one experienced examiner with a linear transducer (6 - 9 MHz,
      LOGIQE9/GE) after a bolus injection of 2.4 ml sulfohexa-fluoride microbubbles
      (SonoVue(r), Bracco, Italy). Retrospective vascular perfusion was quantified by
      evaluating the stored DICOM cine loops using the perfusion software QONTRAST(r)
      (Bracco, Italy). Over a total penetration depth of 3 cm, every centimeter was
      analyzed separately. 27 complications were observed. Complete flap loss was only
      seen in 4 cases, while 23 flaps had to undergo minor revision and survived.
      RESULTS: Regarding the complete flap size, quantitative analysis showed
      significantly higher perfusion values in patients without complications compared
      to patients with complications: PEAK 16.5 vs. 10.0 (p = 0.001), TTP 32.6 vs. 22.2
      (p = 0.001), RBV: 738.8 vs. 246.2 (p < 0.001), RBF 17.5 vs. 10.1 (p < 0.001) and
      MTT 43.1 vs. 29.5 (p = 0.001). Analysis of the correlation of the different flap
      types, age, sex and etiology of the tissue defect to the complication rate showed
      no statistical correlation. CONCLUSION: CEUS was capable of detecting vascular
      disturbances after flap transplantation. TTP, RBV and MTT seem to be the most
      accurately parameters and are not susceptible to malfunction during measurement.

PMID- 24127395
TI  - A comparison of slow, uphill and fast, level walking on lower extremity
      biomechanics and tibiofemoral joint loading in obese and nonobese adults.
AB  - We determined if slow, uphill walking (0.75 m/s, 6 degrees ) reduced tibiofemoral
      (TF) loading compared to faster, level walking (1.50 m/s) in obese and nonobese
      adults. We collected kinematic, kinetic, and electromyographic data as 9
      moderately obese and 10 nonobese participants walked on a dual-belt instrumented
      treadmill. We used OpenSim to scale a musculoskeletal model and calculate joint
      kinematics, kinetics, muscle forces, and TF forces. Compressive TF forces were
      greater in the obese adults during both speed/grade combinations. During level
      walking, obese participants walked with a straighter leg than nonobese
      participants, resulting in early stance vasti muscle forces that were similar in
      the obese and nonobese participants. Early stance peak compressive TF forces were
      reduced by 23% in obese (2,352 to 1,811 N) and 35% in nonobese (1,994 to 1,303 N)
      individuals during slow, uphill walking compared to brisk level walking. Late
      stance peak TF forces were similar across speeds/grades, but were greater in
      obese (~2,900 N) compared to nonobese (~1,700 N) individuals. Smaller early
      stance TF loads and loading rates suggest that slow, uphill walking may be
      appropriate exercise for obese individuals at risk for musculoskeletal pathology
      or pain.

PMID- 24127396
TI  - Facet-dependent catalytic activity of Cu2O nanocrystals in the one-pot synthesis
      of 1,2,3-triazoles by multicomponent click reactions.
AB  - We report the highly facet-dependent catalytic activity of Cu2O nanocubes,
      octahedra, and rhombic dodecahedra for the multicomponent direct synthesis of
      1,2,3-triazoles from the reaction of alkynes, organic halides, and NaN3. The
      catalytic activities of clean surfactant-removed Cu2O nanocrystals with the same
      total surface area were compared. Rhombic dodecahedral Cu2O nanocrystals bounded
      by {110} facets were much more catalytically active than Cu2O octahedra exposing
      {111} facets, whereas Cu2O nanocubes displayed the slowest catalytic activity.
      The superior catalytic activity of Cu2O rhombic dodecahedra is attributed to the
      fully exposed surface Cu atoms on the {110} facet. A large series of 1,4
      disubstituted 1,2,3-triazoles have been synthesized in excellent yields with high
      regioselectivity under green conditions by using these rhombic dodecahedral Cu2O
      catalysts, including the synthesis of rufinamide, an antiepileptic drug,
      demonstrating the potential of these nanocrystals as promising heterogeneous
      catalysts for other important coupling reactions.

PMID- 24127397
TI  - An evaluation of factors that influence children's instruction following.
AB  - Behavior that resembles instruction following might sometimes be under stimulus
      control of extraneous variables. We evaluated the effects of some of these
      variables (i.e., presence of relevant objects, associations between instructions
      and object sets) with 3 children with intellectual disabilities. In Experiment 1,
      we assessed whether subjects were more likely to follow instructions that
      required object manipulation and whether subjects were more likely to follow
      these instructions when only relevant objects were present. All subjects were
      more likely to follow instructions that required object manipulation when only
      relevant objects were present. In Experiment 2, we evaluated whether instruction
      following would be less likely if the same object set was associated with
      multiple instructions, and found this to be the case for 2 of 2 subjects.
      Findings highlight the need to train instruction following under different
      conditions to ensure that responding comes under stimulus control of the
      instructions. 

PMID- 24127398
TI  - Optimization of b-value distribution for biexponential diffusion-weighted MR
      imaging of normal prostate.
AB  - PURPOSE: To determine the optimal b-value distribution for biexponential
      diffusion-weighted imaging (DWI) of normal prostate using both a computer
      modeling approach and in vivo measurements. MATERIALS AND METHODS: Optimal b
      value distributions for the fit of three parameters (fast diffusion Df, slow
      diffusion Ds, and fraction of fast diffusion f) were determined using Monte-Carlo
      simulations. The optimal b-value distribution was calculated using four
      individual optimization methods. Eight healthy volunteers underwent four repeated
      3 Tesla prostate DWI scans using both 16 equally distributed b-values and an
      optimized b-value distribution obtained from the simulations. The b-value
      distributions were compared in terms of measurement reliability and repeatability
      using Shrout-Fleiss analysis. RESULTS: Using low noise levels, the optimal b
      value distribution formed three separate clusters at low (0-400 s/mm2), mid-range
      (650-1200 s/mm2), and high b-values (1700-2000 s/mm2). Higher noise levels
      resulted into less pronounced clustering of b-values. The clustered optimized b
      value distribution demonstrated better measurement reliability and repeatability
      in Shrout-Fleiss analysis compared with 16 equally distributed b-values.
      CONCLUSION: The optimal b-value distribution was found to be a clustered
      distribution with b-values concentrated in the low, mid, and high ranges and was
      shown to improve the estimation quality of biexponential DWI parameters of in
      vivo experiments.

PMID- 24127399
TI  - Pentalenes--from highly reactive antiaromatics to substrates for material
      science.
AB  - Antimatter: Once studied primarily for their antiaromatic properties, pentalenes
      are rapidly becoming important pi-systems for novel electronic materials. Recent
      developments in this area are summarized. 

PMID- 24127400
TI  - M1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver
      lesions; a possible analysis for hepato-pathology.
AB  - "Classically activated macrophages (M1)" and "alternatively activated macrophages
      (M2)", which appear in injured tissues, control either inflammation or
      remodeling. The mechanism remains unclear. To clarify the M1-/M2-macrophage
      polarization in acute liver injury, M1- and M2-related factors were analysed in
      F344 rats by a single injection of TAA (300 mg/kg BW), and liver samples were
      collected on post injection (PI) hour 10 and days 1 to 10. Macrophage
      immunophenotypes were analyzed by single and double immunolabeling. M1-/M2
      related factors were analyzed by real-time RT-PCR. On PI hour 10 (when
      centrilobular lesions were not still developed), expressions of IFN-gamma, TNF
      alpha, IL-1beta, and IL-6 for M1, and IL-4 for M2 were already increased,
      followed by increased expressions of IL-10 and TGF-beta1 for M2 on PI days 1-3
      with development of centrilobular lesions and subsequent reparative fibrosis. On
      PI hour 10, CD204+ and MHC class II+ macrophages already increased in the intact
      periportal/Glisson's sheath regions, accompanied by an increased number of
      granzyme B+ NK cells. Reactive cells at PI hour 10 might produce M1-related
      factors. In addition to these macrophages, CD68+ and CD163+ macrophages, and CD3+
      T cells appeared in the injured centrilobular region on PI days 1-3; there were
      macrophages reacting simultaneously to CD68/MHC class II, CD163/MHC class II,
      CD68/CD204, CD163/CD204, and MHC class II/CD204 in varying degrees. Although
      CD68+ and CD163+ macrophages are regarded as M1- and M2-types, respectively, the
      double labeling indicated that macrophage immunophenotypes are interchangeable in
      injured regions and subsequent fibrosis. An M1-/M2-macrophage paradigm would be
      useful to analyze hepatotoxicity and to understand the pathogenesis.

PMID- 24127401
TI  - Revealing interaction between sulfobutylether-beta-cyclodextrin and reserpine by
      chemiluminescence and site-directed molecular docking.
AB  - The host-guest interaction between sulfobutylether-beta-cyclodextrin (SBE-beta
      CD) and reserpine (RSP) is described using flow injection-chemiluminescence (FI
      CL) and site-directed molecular docking methods. It was found that RSP could
      inhibit the CL intensity produced by a luminol/SBE-beta-CD system. The decrease
      in CL intensity was logarithmic over an RSP concentration range of 0.03 to 700.0
      nM, giving a regression equation of ?I = 107.1lgCRES  + 186.1 with a detection
      limit of 10 pM (3sigma). The CL assay was successfully applied in the
      determination of RSP in injection, saliva and urine samples with recoveries in
      the range 93.5-106.1%. Using the proposed CL model, the binding constant (KCD-R )
      and the stoichiometric ratio of SBE-beta-CD/RSP were calculated to be 7.4 * 10(6)
      M(-1) and 1 : 1, respectively. Using molecular docking, it was confirmed that
      luminol binds to the small cavity of SBE-beta-CD with a nonpolar interaction,
      while RSP targeted the larger cavity of SBE-beta-CD and formed a 1 : 1 complex
      with hydrogen bonds. The proposed new CL method has the potential to become a
      powerful tool for revealing the host-guest interaction between CDs and drugs, as
      well as monitoring drugs with high sensitivity.

PMID- 24127402
TI  - Modified Gaussian estimation for correlated binary data.
AB  - In this paper, we develop a Gaussian estimation (GE) procedure to estimate the
      parameters of a regression model for correlated (longitudinal) binary response
      data using a working correlation matrix. A two-step iterative procedure is
      proposed for estimating the regression parameters by the GE method and the
      correlation parameters by the method of moments. Consistency properties of the
      estimators are discussed. A simulation study was conducted to compare 11
      estimators of the regression parameters, namely, four versions of the GE, five
      versions of the generalized estimating equations (GEEs), and two versions of the
      weighted GEE. Simulations show that (i) the Gaussian estimates have the smallest
      mean square error and best coverage probability if the working correlation
      structure is correctly specified and (ii) when the working correlation structure
      is correctly specified, the GE and the GEE with exchangeable correlation
      structure perform best as opposed to when the correlation structure is
      misspecified. 

PMID- 24127403
TI  - Alexithymia, depression, inflammation, and pain in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: We previously reported that depression and inflammation have
      independent effects on pain severity in patients with rheumatoid arthritis (RA).
      Alexithymia is a personality trait characterized by deficits in cognitive
      processing and regulation of emotions. A broad association between alexithymia
      and various health problems has been suggested, including depression,
      inflammation, and pain. The objective of this study was to examine the
      independent influence of alexithymia on pain perception and its relationship to
      depression and inflammation. METHODS: We evaluated 213 RA outpatients who
      completed self-administered questionnaires, including the Beck Depression
      Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto
      Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog
      scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were
      measured to quantify inflammation severity. RESULTS: An initial significant
      positive association between the TAS-20 score and pain severity (P = 0.01) lost
      significance after controlling for BDI-II score and CRP level using regression
      analysis. An interaction was observed among alexithymia, depression, and
      inflammation with regard to perceived pain. Among those without alexithymia, pain
      severity increased linearly with the CRP tertile levels regardless of the
      presence of depression (P < 0.001 for trend). No linear association between pain
      severity and CRP level was observed among those with alexithymia. Moreover,
      depressed patients with alexithymia (BDI-II score >=14 and TAS-20 score >=61)
      reported severe pain even at low CRP levels. CONCLUSION: Alexithymia might have a
      substantial role in pain perception as well as depression in patients with RA. A
      biopsychosocial approach is essential to achieve better pain control.

PMID- 24127405
TI  - Realistic energy surfaces for real-world systems: an IMOMO CCSD(T):DFT scheme for
      rhodium-catalyzed hydroformylation with the 6-DPPon ligand.
AB  - The hydroformylation of terminal alkenes is one of the most important
      homogeneously catalyzed processes in industry, and the atomistic understanding of
      this reaction has attracted enormous interest in the past. Herein, the whole
      catalytic cycle for rhodium-catalyzed hydroformylation with the 6
      diphenylphosphinopyridine-(2H)-1-one (6-DPPon) ligand 1 was studied. This
      catalytic transformation is challenging to describe computationally, since two
      requirements must be met: 1) changes in the hydrogen-bond network must be modeled
      accurately and 2) bond-formation/bond-breaking processes in the coordination
      sphere of the rhodium center must be calculated accurately. Depending on the
      functionals used (BP86, B3LYP), the results were found to differ strongly.
      Therefore, the complete cycle was calculated by using highly accurate CCSD(T)
      computations for a PH3 model ligand. By applying an integrated molecular orbital
      plus molecular orbital (IMOMO) method consisting of CCSD(T) as high level and DFT
      as low-level method, excellent agreement between the two functionals was
      achieved. To further test the reliability of the calculations, the energetic-span
      model was used to compare experimentally derived and computed activation
      barriers. The accuracy of the new IMOMO method apparently makes it possible to
      predict the catalytic potential of real-world systems.

PMID- 24127406
TI  - Multiplex detection of DNA mutations by the fluorescence fingerprint spectrum
      technique.
AB  - A fingerprint spectrum technique that utilizes cationic conjugated-polymer-based
      fluorescence resonance energy transfer (FRET) is used for multiplex detection of
      DNA mutations. This method detects as low as 5 % mutation of the total DNA. Ten
      PIK3CA mutations originating from 30 clinical breast cancer samples could be
      detected. 

PMID- 24127404
TI  - Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin
      degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T
      lymphocytes.
AB  - Varieties of transforming growth factor-beta (TGF-beta) antagonists have been
      developed to intervene with excessive TGF-beta signalling activity in cancer.
      Activin receptor-like kinase5 (ALK5) inhibitors antagonize TGF-beta signalling by
      blocking TGF-beta receptor-activated Smad (R-Smad) phosphorylation. Here we
      report the novel mechanisms how ALK5 inhibitors exert a therapeutic effect on a
      mouse B16 melanoma model. Oral treatment with a novel ALK5 inhibitor, EW-7197
      (2.5 mg/kg daily) or a representative ALK5 inhibitor, LY-2157299 (75 mg/kg bid)
      suppressed the progression of melanoma with enhanced cytotoxic T-lymphocyte (CTL)
      responses. Notably, ALK5 inhibitors not only blocked R-Smad phosphorylation, but
      also induced ubiquitin-mediated degradation of the common Smad, Smad4 mainly in
      CD8(+) T cells in melanoma-bearing mice. Accordingly, T-cell-specific deletion of
      Smad4 was sufficient to suppress the progression of melanoma. We further
      identified eomesodermin (Eomes), the T-box transcription factor regulating CTL
      functions, as a specific target repressed by TGF-beta via Smad4 and Smad3 in
      CD8(+) T cells. Thus, ALK5 inhibition enhances anti-melanoma CTL responses
      through ubiquitin-mediated degradation of Smad4 in addition to the direct
      inhibitory effect on R-Smad phosphorylation.

PMID- 24127407
TI  - CreER(T2) expression from within the c-Kit gene locus allows efficient inducible
      gene targeting in and ablation of mast cells.
AB  - Mast cells are abundantly situated at contact sites between the body and its
      environment, such as the skin and, especially during certain immune responses, at
      mucosal surfaces. They mediate allergic reactions and degrade toxins as well as
      venoms. However, their roles during innate and adaptive immune responses remain
      controversial and it is likely that major functions remain to be discovered.
      Recent developments in mast cell-specific conditional gene targeting in the mouse
      promise to enhance our understanding of these fascinating cells. To complete the
      genetic toolbox to study mast cell development, homeostasis and function, it is
      imperative to inducibly manipulate their gene expression. Here, we report the
      generation of a novel knock-in mouse line expressing a tamoxifen-inducible
      version of the Cre recombinase from within the endogenous c-Kit locus. We
      demonstrate highly efficient and specific inducible expression of a fluorescent
      reporter protein in mast cells both in vivo and in vitro. Furthermore, induction
      of diphtheria toxin A expression allowed selective and efficient ablation of mast
      cells at various anatomical locations, while other hematopoietic cells remain
      unaffected. This novel mouse strain will hence be very valuable to study mast
      cell homeostasis and how specific genes influence their functions in physiology
      and pathology. 

PMID- 24127408
TI  - Binding study of lysozyme with Al(III) using chemiluminescence analysis.
AB  - The binding behavior of lysozyme with Al(III) is described using luminol as a
      luminescence probe by flow injection-chemiluminescence (FI-CL) analysis. It was
      found that the CL intensity of the luminol-lysozyme reaction could be markedly
      enhanced by Al(III), and the increase in CL intensity was linear with the Al(III)
      concentration over the range 0.3-30.0  pg  mL(-1) , with a detection limit of 0.1
      pg  mL(-1) (3sigma). Based on the interaction model of lysozyme with Al(III),
      lg[(I - I0 )/(2I0  - I)] = lgK + nlg[M], the binding constant K = 6.84 * 10(6)  L
      mol(-1) and the number of binding sites (n) = 0.76. The relative standard
      deviations were 3.2, 2.4 and 2.0% for 10.0, 20.0 and 30.0  pg  mL(-1) Al(III) (n
      = 7), respectively. This new method was successfully applied to continuous,
      quantitative monitoring of picogram level Al(III) in human saliva following oral
      intake of compound aluminum hydroxide tablets. It was found that Al(III) in
      saliva reached a maximum of 101.2  ng  mL(-1) at 3.0 h. The absorption rate
      constant ka , elimination rate constant k and half-life time t1/2 of Al(III) were
      1.378  h(-1) , 0.264  h(-1) and 2.624  h, respectively.

PMID- 24127409
TI  - Connective tissue growth factor (CTGF/CCN2) negatively regulates BMP-2 induced
      osteoblast differentiation and signaling.
AB  - Connective tissue growth factor (CTGF/CCN2) and bone morphogenetic protein (BMP)
      2 are both produced and secreted by osteoblasts. Both proteins have been shown to
      have independent effects in regulating osteoblast proliferation, maturation and
      mineralization. However, how these two proteins interact during osteoblast
      differentiation remains unknown. In this study, we utilized two cell culture
      model systems, osteoblasts derived from CTGF knockout (KO) mice and osteoblasts
      infected with an adenovirus which over-expresses CTGF (Ad-CTGF), to investigate
      the effects of CTGF and BMP-2 on osteoblast development and function in vitro.
      Contrary to a previously published report, osteoblast maturation and
      mineralization were similar in osteogenic cultures derived from KO and WT
      calvaria in the absence of BMP-2 stimulation. Interestingly, in KO and WT
      osteoblast cultures stimulated with BMP-2, the KO osteoblasts exhibited enhanced
      osteoblast differentiation. This increase in osteoblast differentiation was
      accompanied by increased protein levels of phosphorylated Smad 1/5/8 and mRNA
      expression levels of bone morphogenetic protein receptor Ib. We also examined
      osteoblast differentiation in cultures that were infected with an adenoviral-CTGF
      vector (Ad-CTGF) and in controls. Continuous over-expression of CTGF resulted in
      decreased osteoblast maturation and mineralization in both unstimulated and BMP-2
      stimulated cultures. Impaired osteoblast differentiation in cultures over
      expressing CTGF was accompanied by decreased protein levels of phosphorylated
      Smad 1/5/8. Collectively, the data from these studies demonstrate that CTGF acts
      to negatively regulate BMP-2 induced signaling and osteoblast differentiation,
      and warrant additional studies to determine the precise mechanism(s) responsible
      for this effect. J. Cell. Physiol. 229: 672-681, 2014. (c) 2013 Wiley
      Periodicals, Inc. 

PMID- 24127410
TI  - An approach to benzophosphole oxides through silver- or manganese-mediated
      dehydrogenative annulation involving C-C and C-P bond formation.
AB  - Benzophosphole construction was achieved through the Ag(I) -mediated
      dehydrogenative annulation of phenylphosphine oxides with internal alkynes in a
      process involving C?C and C?P bond formation. A wide range of asymmetrical
      phenylacetylenes could be employed and the reactions proceeded with perfect
      regioselectivity. Moreover, the annulation could be conducted even at room
      temperature when a Mn(III) promoter was used in place of Ag(I) . 

PMID- 24127411
TI  - Rectal cancer: dynamic contrast-enhanced MRI correlates with lymph node status
      and epidermal growth factor receptor expression.
AB  - PURPOSE: To evaluate correlations between dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) and clinicopathologic data as well as immunostaining
      of the markers of angiogenesis epidermal growth factor receptor (EGFR) and CXC
      motif chemokine receptor 4 (CXCR4) in patients with rectal cancer. MATERIALS AND
      METHODS: Presurgical DCE-MRI was performed in 41 patients according to a
      standardized protocol. Two quantitative parameters (k21 , A) were derived from a
      pharmacokinetic two-compartment model, and one semiquantitative parameter (TTP)
      was assessed. Standardized surgery and histopathologic examinations were
      performed in all patients. Immunostaining for EGFR and CXCR4 was performed and
      evaluated with a standardized scoring system. RESULTS: DCE-MRI parameter A
      correlated significantly with the N category (P = 0.048) and k21 with the
      occurrence of synchronous and metachronous distant metastases (P = 0.029). A
      trend was shown toward a correlation between k21 and EGFR expression (P = 0.107).
      A significant correlation was found between DCE-MRI parameter TTP and the
      expression of EGFR (P = 0.044). DCE-MRI data did not correlate with CXCR4
      expression. CONCLUSION: DCE-MRI is a noninvasive method which can characterize
      microcirculation in rectal cancer and correlates with EGFR expression. Given the
      relationship between the dynamic parameters and the clinicopathologic data, DCE
      MRI data may constitute a prognostic indicator for lymph node and distant
      metastases in patients with rectal cancer.

PMID- 24127412
TI  - Aptamer-based thrombin assay on microfluidic platform.
AB  - A facile and sensitive aptamer-based protocol has been developed for protein
      assay on microfluidic platform with fluorescence detection using an off-chip
      microarray scanner. Aptamer-functionalized magnetic beads were used to capture
      thrombin that binds to a second aptamer fluorescently labeled by Cy3.
      Experimental conditions, such as incubation time and temperature, washing time,
      interfering proteins, and aptamer, etc., were optimized for the microchip method.
      This work demonstrated there was a good relationship between fluorescence
      intensity and thrombin concentration in the range of 65-1000 ng/mL with the RSD
      less than 8%. Notably, an analysis only needs 1 MUL volume of sample injection
      and this system can capture extremely tiny amount thrombin (0.4 fmol). This
      method has been successfully applied to assay of thrombin in human serum with the
      recovery of 79.74-95.94%. 

PMID- 24127413
TI  - Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR
      483-5p as a potential biomarker.
AB  - BACKGROUND: MicroRNAs (miRNA) are abundant in the circulation and play a central
      role in diverse biologic processes; they may be useful for early diagnosis of
      hepatocellular carcinoma. METHODS: We conducted a two-phase, case-control study
      (20 pairs for the discovery set and 49 pairs for the validation set) to test the
      hypothesis that genome-wide dysregulation of circulating miRNAs differentiates
      hepatocellular carcinoma cases from controls. Taqman low-density arrays were used
      to examine genome-wide miRNA expression for the discovery set, and quantitative
      real-time PCR was used to validate candidate miRNAs for both discovery and
      validation sets. RESULTS: Sixty-six miRNAs were found to be significantly
      overexpressed in plasma of hepatocellular carcinoma cases compared with controls
      after adjusting for false discovery rate (P < 0.05). A volcano plot indicated
      that seven miRNAs had greater than 2-fold case-control differences with P < 0.01.
      Four significant miRNAs (miR-150, miR-30c, miR-483-5p, and miR-520b) detectable
      in all samples with varied expression levels were further validated in a
      validation set. MiR-483-5p was statistically significantly overexpressed in
      hepatocellular carcinoma cases compared with controls (3.20 vs. 0.82, P <
      0.0001). Hepatocellular carcinoma risk factors and clinic-pathological
      characteristics did not influence miR-483-5p expression. The combination of
      plasma miR-483-5p level and hepatitis C virus status can significantly
      differentiate hepatocellular carcinoma cases from controls with an area under the
      curve of 0.908 (P < 0.0001). The sensitivity and specificity were, respectively,
      75.5% and 89.8%. CONCLUSIONS: These preliminary results suggest the importance of
      dysregulated circulating miR-483-5p as a potential hepatocellular carcinoma
      biomarker. IMPACT: Confirmation of aberrant expression of miR-483-5p in a large
      prospective hepatocellular carcinoma study will provide support for its
      application to hepatocellular carcinoma detection.

PMID- 24127414
TI  - Body mass index and microsatellite instability in colorectal cancer: a population
      based study.
AB  - BACKGROUND: Previous studies reported a positive association of body mass index
      (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI
      high) colorectal cancer. However, information from population-based studies
      conducted in representative age groups is so far limited. METHODS: We conducted a
      population-based case-control study (DACHS) in Southern Germany, including 1,215
      patients with incident colorectal cancer and 1,891 matched controls with no upper
      age limit. Information on risk factors of colorectal cancer was obtained in
      standardized interviews. Microsatellite instability was analyzed using a
      mononucleotide marker panel. RESULTS: Median age among cases was 69 years, and
      115 cases were classified MSI-high (9.5%). In multivariate analyses, BMI was
      positively associated with both risk of MSI-high colorectal cancer [per 5
      kg/m(2): OR, 1.71; 95% confidence interval (CI), 1.35-2.17] and risk of MSS
      colorectal cancer (OR, 1.20; 95% CI, 1.07-1.33). The association with MSI-high
      colorectal cancer was limited to women (OR, 2.04; 95% CI, 1.50-2.77; P
      interaction = 0.02) and most pronounced among ever users of postmenopausal
      hormone replacement therapy (OR, 4.68; 95% CI, 2.36-9.30; P interaction = 0.01).
      In case-only analyses, BMI was more strongly associated with MSI-high colorectal
      cancer than with MSS colorectal cancer among women (OR, 1.84; 95% CI, 1.13-1.82;
      P interaction = 0.01). CONCLUSIONS: This population-based study confirms previous
      findings of increased risk of MSS colorectal cancer with obesity between both
      sexes and suggests that overweight and obesity may also be associated with
      increased risk of MSI-high colorectal cancer among women. IMPACT: These findings
      extend available data on the association of BMI and microsatellite instability in
      colorectal cancer and may suggest a link between overweight and obesity with
      sporadic MSI-high colorectal cancer in women.

PMID- 24127416
TI  - Comparison of composite measures of disease activity in psoriatic arthritis using
      data from an interventional study with golimumab.
AB  - OBJECTIVE: To compare the performance of the Psoriatic Arthritis Disease Activity
      Score (PASDAS), the Arithmetic Mean of the Desirability Function (AMDF), the
      Composite Psoriatic Disease Activity Index (CPDAI), and the Disease Activity
      Index for Psoriatic Arthritis (DAPSA) in the GO-REVEAL data set. The Disease
      Activity Score using 28 joints (DAS28) was used as a comparator. METHODS: The GO
      REVEAL study did not allow full computation of all the composite scores (a
      modified version of CPDAI was used). The performance of the scores at baseline
      and followup (weeks 14 and 24) was compared using effect sizes. RESULTS: All
      indices could distinguish response to treatment at 14 and 24 weeks. Effect sizes
      at 24 weeks for the 50 mg (100 mg) golimumab doses were 2.18 (2.36), 2.08 (2.36),
      1.09 (1.41), 1.80 (1.78), and 1.13 (1.18) for PASDAS, AMDF, modified CPDAI,
      DAS28, and DAPSA, respectively. Comparison of 24-week values across the 3
      treatment groups (placebo, golimumab 50 mg, and golimumab 100 mg) by an analysis
      of covariance using the baseline values as covariates gave the following F
      statistics: PASDAS 18.3, AMDF 19.6, modified CPDAI 9.4, DAS28 13.6, and DAPSA
      7.9; all of these are highly significant. When the analysis was confined to the 2
      golimumab treatment groups, there were no significant between-treatment group
      differences with any of the composite measures. CONCLUSION: PASDAS and AMDF were
      better able to distinguish treatment effect, having larger effect sizes at 24
      weeks. PASDAS, AMDF, and modified CPDAI better reflected domains such as skin,
      enthesitis, and dactylitis.

PMID- 24127415
TI  - A major role for RCAN1 in atherosclerosis progression.
AB  - Atherosclerosis is a complex inflammatory disease involving extensive vascular
      vessel remodelling and migration of vascular cells. As RCAN1 is implicated in
      cell migration, we investigated its contribution to atherosclerosis. We show
      RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed
      in lesional macrophages, endothelial cells and vascular smooth muscle cells and
      was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1
      regulates CD36 expression and its genetic inactivation reduced atherosclerosis
      extension and severity in Apoe(-/-) mice. This effect was mechanistically linked
      to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage
      migration and increased lesional IL-10 and mannose receptor expression. Moreover,
      Apoe(-/-) Rcan1(-/-) macrophages expressed higher-than-Apoe(-/-) levels of anti
      inflammatory markers. We previously showed that Rcan1 mediates aneurysm
      development and that its expression is not required in haematopoietic cells for
      this process. However, transplantation of Apoe(-/-) Rcan1(-/-) bone-marrow (BM)
      cells into Apoe(-/-) recipients confers atherosclerosis resistance. Our data
      define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that
      therapies aimed at inhibiting RCAN1 expression or function might significantly
      reduce atherosclerosis burden. 

PMID- 24127417
TI  - Cyclodextrin-assisted synthesis of a metallosupramolecular terbium(III) polymer
      and its fluorescence properties and chiral recognition.
AB  - Hold and connect! Inclusion of a bridging ligand into cyclodextrin (CD), followed
      by the addition of Tb(III) leads to a polyrotaxane-type metallosupramolecular
      polymer (see figure, L=4,4'-biphenyldicarboxylic acid). This polymer can
      recognize chirality and differentiate enantiomers by fluorescence and circular
      dichroism spectral changes. 

PMID- 24127418
TI  - Letter to the editor, "the amazing odontoblast: activity, autophagy, and aging".

PMID- 24127419
TI  - Response to letter to the editor, "the amazing odontoblast: activity, autophagy,
      and aging": why rename the amazing odontoblast?

PMID- 24127420
TI  - Total synthesis and biological evaluation of jerantinine E.

PMID- 24127421
TI  - Response to "High BMI at diagnosis is associated with inferior survival in
      patients with osteosarcoma".

PMID- 24127422
TI  - Nuclear spin isomers of ethylene: enrichment by chemical synthesis and
      application for NMR signal enhancement.

PMID- 24127423
TI  - Decreased bone formation and increased osteoclastogenesis cause bone loss in
      mucolipidosis II.
AB  - Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused
      by missorting of lysosomal proteins and the subsequent lysosomal storage of
      undegraded macromolecules. Although affected children develop disabling skeletal
      abnormalities, their pathogenesis is not understood. Here we report that MLII
      knock-in mice, recapitulating the human storage disease, are runted with
      accompanying growth plate widening, low trabecular bone mass and cortical
      porosity. Intralysosomal deficiency of numerous acid hydrolases results in
      accumulation of storage material in chondrocytes and osteoblasts, and impaired
      bone formation. In osteoclasts, no morphological or functional abnormalities are
      detected whereas osteoclastogenesis is dramatically increased in MLII mice. The
      high number of osteoclasts in MLII is associated with enhanced osteoblastic
      expression of the pro-osteoclastogenic cytokine interleukin-6, and
      pharmacological inhibition of bone resorption prevented the osteoporotic
      phenotype of MLII mice. Our findings show that progressive bone loss in MLII is
      due to the presence of dysfunctional osteoblasts combined with excessive
      osteoclastogenesis. They further underscore the importance of a deep skeletal
      phenotyping approach for other lysosomal diseases in which bone loss is a
      prominent feature. 

PMID- 24127424
TI  - The synthesis of methylated, phosphorylated, and phosphonated 3'-aminoacyl
      tRNA(Sec) mimics.
AB  - The twenty first amino acid, selenocysteine (Sec), is the only amino acid that is
      synthesized on its cognate transfer RNA (tRNA(Sec)) in all domains of life. The
      multistep pathway involves O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase
      (SepSecS), an enzyme that catalyzes the terminal chemical reaction during which
      the phosphoseryl-tRNA(Sec) intermediate is converted into selenocysteinyl
      tRNA(Sec). The SepSecS architecture and the mode of tRNA(Sec) recognition have
      been recently determined at atomic resolution. The crystal structure provided
      valuable insights that gave rise to mechanistic proposals that could not be
      validated because of the lack of appropriate molecular probes. To further improve
      our understanding of the mechanism of the biosynthesis of selenocysteine in
      general and the mechanism of SepSecS in particular, stable tRNA(Sec) substrates
      carrying aminoacyl moieties that mimic particular reaction intermediates are
      needed. Here, we report on the accurate synthesis of methylated, phosphorylated,
      and phosphonated serinyl-derived tRNA(Sec) mimics that contain a hydrolysis
      resistant ribose 3'-amide linkage instead of the natural ester bond. The
      procedures introduced allow for efficient site-specific methylation and/or
      phosphorylation directly on the solid support utilized in the automated RNA
      synthesis. For the preparation of (S)-2-amino-4-phosphonobutyric acid
      oligoribonucleotide conjugates, a separate solid support was generated.
      Furthermore, we developed a three-strand enzymatic ligation protocol to obtain
      the corresponding full-length tRNA(Sec) derivatives. Finally, we developed an
      electrophoretic mobility shift assay (EMSA) for rapid, qualitative
      characterization of the SepSecS-tRNA interactions. The novel tRNA(Sec) mimics are
      promising candidates for further elucidation of the biosynthesis of
      selenocysteine by X-ray crystallography and other biochemical approaches, and
      could be attractive for similar studies on other tRNA-dependent enzymes.

PMID- 24127425
TI  - A cortical network for the encoding of object change.
AB  - Understanding events often requires recognizing unique stimuli as alternative,
      mutually exclusive states of the same persisting object. Using fMRI, we examined
      the neural mechanisms underlying the representation of object states and object
      state changes. We found that subjective ratings of visual dissimilarity between a
      depicted object and an unseen alternative state of that object predicted the
      corresponding multivoxel pattern dissimilarity in early visual cortex during an
      imagery task, while late visual cortex patterns tracked dissimilarity among
      distinct objects. Early visual cortex pattern dissimilarity for object states in
      turn predicted the level of activation in an area of left posterior ventrolateral
      prefrontal cortex (pVLPFC) most responsive to conflict in a separate Stroop color
      word interference task, and an area of left ventral posterior parietal cortex
      (vPPC) implicated in the relational binding of semantic features. We suggest that
      when visualizing object states, representational content instantiated across
      early and late visual cortex is modulated by processes in left pVLPFC and left
      vPPC that support selection and binding, and ultimately event comprehension. 

PMID- 24127426
TI  - Sex differences in the limit to deficit accumulation in late middle-aged and
      older Chinese people: results from the Beijing Longitudinal Study of Aging.
AB  - BACKGROUND: On average, as people age, they accumulate more health deficits and
      have an increased risk of death. The deficit accumulation-based frailty index
      (FI) can quantify health and its outcomes in aging. Previous studies have
      suggested that women show higher FI values than men and that the highest FI score
      (the "limit to frailty") occurs at a value of FI ~ 0.7. Even so, gender
      differences in the limit to frailty have not been reported. METHODS: Data for
      this analysis were obtained from the Beijing Longitudinal Study of Aging that
      involved 3,257 community-dwelling Chinese people, aged 55+ years at baseline. The
      main outcome measure was 5-year mortality. An FI consisting of 35 health-related
      variables was constructed. The absolute and 99% FI limits were calculated for
      different age groups and analyzed by sex. RESULTS: The mean level of the FI
      increased with age and was lower in men than in women (F = 67.87, p < .001). The
      99% FI limit leveled off slightly earlier with a relatively lower value in men
      (60 years; 0.44 +/- 0.02) compared with that in women (65 years; 0.52 +/- 0.04).
      The highest absolute FI value was 0.61 in men and 0.69 in women. In both groups,
      people with an FI greater than or equal to the 99% limit showed close to 100%
      mortality by 5 years. CONCLUSION: Compared with men, women appeared to better
      tolerate deficits in health, yielding both relatively lower mortality and higher
      limit values to the FI. Even so, the FI did not exceed 0.7 in any individual.

PMID- 24127427
TI  - Serum carboxymethyl-lysine, disability, and frailty in older persons: the
      Cardiovascular Health Study.
AB  - BACKGROUND: Advanced glycation endproducts are biologically active compounds that
      accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML),
      a ubiquitous human advanced glycation endproduct, has been associated with age
      related conditions and mortality. Our objective was to ascertain the relationship
      between CML and geriatric outcomes (disability and frailty) in a large cohort of
      older men and women. METHODS: In 1996-1997, serum CML was measured in 3,373
      Cardiovascular Health Study participants (mean age 78.1 +/- 4.8 years).
      Disability, defined as difficulty in any of six activities of daily living, was
      assessed every 6-12 months for 14 years. Frailty was defined according to five
      standard criteria at the 1996-1997 visit. Cox proportional hazard models
      estimated the relationship between CML and incident disability (N = 2,643).
      Logistic regression models estimated the relationship between CML and prevalent
      frailty. RESULTS: Adjusting for multiple potential confounders, higher CML was
      associated with incident disability (hazard ratio per standard deviation [225
      ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with
      higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48),
      but the relationship was attenuated by adjustment for cognitive status, kidney
      function, and arthritis. CML was not associated with frailty in women.
      CONCLUSIONS: Higher serum CML levels in late life are associated with incident
      disability and prevalent frailty. Further work is needed to understand CML's
      value as a risk stratifier, biomarker, or target for interventions that promote
      healthy aging.

PMID- 24127428
TI  - Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with
      men.
AB  - BACKGROUND: Adults aging with HIV infection are at risk for age-related
      comorbidities and syndromes, such as frailty. The objective of this study was to
      evaluate the expression and predictors of the frailty phenotype (FP) among HIV
      infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men. METHODS: A
      prospective, observational cohort study was nested in the Multicenter AIDS Cohort
      Study from October 2007-September 2011. FP conversion was defined as the onset of
      FP over two consecutive study visits. Adjusted odds ratios and 95% confidence
      intervals ([,]) for FP conversion were estimated using logistic regression models
      with generalized estimating equations. RESULTS: Of 10,571 completed study visits
      from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV-
      men, respectively (p = .002). The proportion of FP+ visits increased with age
      regardless of HIV status, but was significantly greater in HIV+ compared to HIV-
      men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by
      participants, 5% (537) were classified as FP conversion, and 45% of the men with
      FP conversion had only one FP+ study visit. FP conversion was significantly
      associated with a history of AIDS (adjusted odds ratios = 2.26 [1.50, 3.39], but
      not with HIV+ alone (adjusted odds ratios = 1.26 [0.98, 1.64]). Among men who had
      one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two
      comorbidities. CONCLUSIONS: These findings suggest that expression of the FP can
      be measured in men who have sex with men with and without HIV infection and
      reflects multisystem dysfunction in this population; further investigations are
      needed to better understand clinical utility.

PMID- 24127429
TI  - Aging-associated reductions in lipolytic and mitochondrial proteins in mouse
      adipose tissue are not rescued by metformin treatment.
AB  - Mitochondrial enzyme expression is reduced in adipose tissue from old mice, yet
      little is known regarding mechanisms that could be mediating, or interventions
      that could be used, to reverse these changes. The purpose of this study was to
      examine the relationship between lipolytic and fatty acid reesterification
      enzymes, 5' adenosine monophosphate-activated protein kinase and mitochondrial
      proteins in adipose tissue from young versus old mice. A second aim was to
      determine whether metformin treatment could rescue the age-associated decline in
      adipose tissue mitochondrial proteins. Approximately 22-month-old male C57BL/6
      mice were fed a diet with or without 0.5% metformin for 8 weeks. Compared with
      young mice (~11 wk of age), the protein content/phosphorylation of hormone
      sensitive lipase, adipose tissue triglyceride lipase, and phosphoenolpyruvate
      carboxykinase were reduced in old mice. This was paralleled by increases in the
      plasma nonesterified fatty acid:glycerol ratio and reductions in adipose tissue
      5' adenosine monophosphate-activated protein kinase activity and select
      mitochondrial proteins in old mice. There were no differences in these variables
      when comparing adipose tissue from young and 6-month-old mice. While metformin
      improved glucose homeostasis, it did not increase 5' adenosine monophosphate
      activated protein kinase phosphorylation or mitochondrial enzymes. Our findings
      demonstrate a co-ordinated down regulation of lipolytic, reesterification, and
      mitochondrial enzymes in adipose tissue with aging that is unresponsive to
      metformin treatment. 

PMID- 24127430
TI  - High BMI at diagnosis is not associated with inferior survival in patients with
      osteosarcoma. A report from the Cooperative Osteosarcoma Study Group.

PMID- 24127432
TI  - Age-related neurochemical changes in the rhesus macaque cochlear nucleus.
AB  - Neurochemical changes in the expression of various proteins within the central
      auditory system have been associated with natural aging. These changes may
      compensate in part for the loss of auditory sensitivity arising from two
      phenomena of the aging auditory system: cochlear histopathologies and increased
      excitability of central auditory neurons. Recent studies in the macaque monkey
      have revealed age-related changes in the density of nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase (NADPHd) and parvalbumin (PV)-positive
      cells within the inferior colliculus and superior olivary complex. The cochlear
      nucleus (CN), which is the first central auditory nucleus, remains unstudied.
      Since the CN participates in the generation of the auditory brainstem response
      (ABR) and receives direct innervation from the cochlea, it serves as an ideal
      nucleus to compare the relationship between these neurochemical changes and the
      physiological and peripheral changes of the aging auditory system. We used
      stereological sampling to calculate the densities of NADPHd and PV reactive
      neurons within the three subdivisions of the CN in middle-aged and aged rhesus
      macaques. Regression analyses of these values with ABR properties and cochlear
      histopathologies revealed relationships between these cell types and the changing
      characteristics of the aging auditory system. Our results indicate that NADPHd
      expression does change with age in a specific subdivision of the CN, but PV does
      not. Conversely, PV expression correlated with ABR amplitudes and outer hair cell
      loss in the cochlea, but NADPHd did not. These results indicate that NADPHd and
      PV may take part in distinct compensatory efforts of the aging auditory system.

PMID- 24127434
TI  - Correction.

PMID- 24127433
TI  - Subcellular transcriptomics-dissection of the mRNA composition in the axonal
      compartment of sensory neurons.
AB  - RNA localization is a regulatory mechanism that is conserved from bacteria to
      mammals. Yet, little is known about the mechanism and the logic that govern the
      distribution of RNA transcripts within the cell. Here, we present a novel organ
      culture system, which enables the isolation of RNA specifically from NGF
      dependent re-growing peripheral axons of mouse embryo, sensory neurons. In
      combination with massive parallel sequencing technology, we determine the
      subcellular localization of most transcripts in the transcriptome. We found that
      the axon is enriched in mRNAs that encode secreted proteins, transcription
      factors, and the translation machinery. In contrast, the axon was largely
      depleted from mRNAs encoding transmembrane proteins, a particularly interesting
      finding, since many of these gene products are specifically expressed in the tip
      of the axon at the protein level. Comparison of the mitochondrial mRNAs encoded
      in the nucleus with those encoded in the mitochondria, uncovered completely
      different localization pattern, with the latter much enriched in the axon
      fraction. This discovery is intriguing since the protein products encoded by the
      nuclear and mitochondrial genome form large co-complexes. Finally, focusing on
      alternative splice variants that are specific to axonal fractions, we find short
      sequence motifs that are enriched in the axonal transcriptome. Together our
      findings shed light on the extensive role of RNA localization and its
      characteristics.

PMID- 24127435
TI  - Moving Forward With a Clear Definition of Continuing Competence.

PMID- 24127437
TI  - Molecular neuroanatomy and chemoarchitecture of the neurosecretory preoptic
      hypothalamic area in zebrafish larvae.
AB  - The paraventricular nucleus (PVN) in mammals is the main hypothalamic nucleus
      controlling hormone release in the pituitary and plays pivotal roles in
      homeostasis. While the location of a PVN-homologous region has been described in
      adult fish as the neurosecretory preoptic area (NPO), this region has not been
      clearly defined in larval zebrafish due to the difficulty in defining
      cytoarchitectonic nuclear boundaries in the larval brain. Here we identify the
      precise location of the larval zebrafish NPO using conserved transcription factor
      and neuropeptide gene expressions. Our results identify the dorsal half of the
      preoptic-hypothalamic orthopedia a (otpa) domain as the larval NPO and the
      homologous region to the mammalian PVN. Further, by reconstructing the locations
      of cells producing zebrafish neuropeptides found in the mammalian PVN (CCK, CRH,
      ENK, NTS, SS, VIP, OXT, AVP), we provide the first 3D arrangement map of NPO
      neuropeptides in the larval zebrafish brain. Our results show striking
      conservation of transcription factor expression (otp, arx, dlx5a, isl1) in and
      around the NPO/PVN together with neuropeptide expression within it. Finally, we
      describe the exact anatomical location of cells producing Oxt and Avp in the
      adult zebrafish. Thus, our results identify the definitive borders and extent of
      the PVN homologous region in larval zebrafish and serve as an important basis for
      cross-species comparisons of PVN/NPO structure and function.

PMID- 24127438
TI  - What is an anatomy ontology?

PMID- 24127436
TI  - Pulmonary outcomes in survivors of childhood central nervous system malignancies:
      a report from the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Adult survivors of childhood central nervous system (CNS) tumors may
      be at risk for pulmonary dysfunction. This study enumerates the incidence of
      pulmonary dysfunction and explores associations between craniospinal irradiation
      (CSI) and pulmonary dysfunction among survivors of childhood CNS tumors. METHODS:
      Participants included Childhood Cancer Survivor Study (CCSS) cohort members
      treated for CNS malignancies when <age 21, who survived 5+ years, and sibling
      comparisons. Medical records were abstracted and participants completed
      questionnaires that asked about the nature and timing of pulmonary dysfunction.
      Incidence rates were calculated, and Poisson regression, adjusted for
      chemotherapy exposures, was used to evaluate associations between CSI and
      pulmonary dysfunction. RESULTS: Survivor participants (N = 1,653) were 54.7%
      male, median age at diagnosis 7.6 (range 0-21), and median time from cohort entry
      18.5 (range 3.3-33.9) years. The incidence of pulmonary dysfunction (per 1,000
      person years) was 9.1 (95% CI 7.8-10.6) for emphysema/obliterative bronchiolitis
      and >3.0 for asthma, chronic cough and need for extra oxygen. Rates of fibrosis
      (RR 2.0, 95% CI 1.0-3.9), chest wall abnormalities (RR 19.0, 95% CI 4.2-85.7),
      chronic cough (RR 1.6, 95% CI 1.2-2.1) and need for supplemental oxygen (RR 2.5,
      95% CI 1.9-3.3) were higher among survivors than among siblings. Survivors
      treated with CSI were 10.4 (95% CI 7.6-14.4) times more likely than those not
      exposed to report chest wall deformity. CONCLUSION: Adult survivors of CNS
      malignancy have high rates of pulmonary dysfunction 5+ years after diagnosis.
      Survivors treated with CSI should be monitored for pulmonary disease to permit
      early interventions.

PMID- 24127440
TI  - Classic case of unicentric mixed-type Castleman's disease.

PMID- 24127439
TI  - BIRC5 (survivin) splice variant expression correlates with refractory disease and
      poor outcome in pediatric acute myeloid leukemia: a report from the Children's
      Oncology Group.
AB  - BACKGROUND: The inhibitor-of-apoptosis protein survivin, encoded by BIRC5,
      regulates apoptosis, cell division and proliferation. Several survivin splice
      variants have been described however, the prognostic significance of their
      expression has not been well defined in pediatric acute myeloid leukemia (AML).
      PROCEDURE: Quantitative expression analyses of BIRC5 mRNA (n = 306) and survivin
      transcript splice variants (n = 90) were performed on diagnostic bone marrow
      samples from children with de novo AML treated on the clinical trials CCG-2961
      and AAML03P1, then correlated with disease characteristics and clinical outcome.
      RESULTS: Total BIRC5 expression did not correlate with clinical outcome. Fragment
      length analysis and sequencing of the entire BIRC5 transcript demonstrated three
      splice variants. The most prominent product, wild-type survivin, was expressed in
      all samples tested. Two minor transcripts were present in 90 patients treated on
      CCG-2961; survivin-2B and a novel variant, survivin-DeltaEx2, characterized by
      deletion of BIRC5 exon II. A high 2B/DeltaEx2 expression ratio (>=1) correlated
      with increased diagnostic WBC count, monocytic phenotype, +8 cytogenetics, lower
      complete remission (45% [n = 10] vs. 88% [n = 59], P < 0.001) and higher
      induction failure rates (23% [n = 5] vs. 3% [n = 2], P = 0.009). Consistent with
      this poor induction response, patients with a 2B/DeltaEx2 ratio >=1 had inferior
      5-year survival rates (OS 36% vs. 60%, P = 0.011; EFS 23% vs. 53% at 5 years, P =
      0.001) and appear to have increased relapse risk (P = 0.056). Subset analyses
      suggest that relative over-expression of 2B, rather than under-expression of
      DeltaEx2 determines clinical response. CONCLUSIONS: High survivin-2B/DeltaEx2
      ratios are associated with refractory disease and inferior survival in childhood
      AML. Survivin splice variant expression warrants prospective evaluation in
      clinical trials.

PMID- 24127441
TI  - Evolution of clinical trial design in early drug development: systematic review
      of expansion cohort use in single-agent phase I cancer trials.
AB  - PURPOSE: To evaluate the use and objectives of expansion cohorts in phase I
      cancer trials and to explore trial characteristics associated with their use.
      METHODS: We performed a systematic review of MEDLINE and EMBASE, limiting studies
      to single-agent phase I trials recruiting adults and published after 2006.
      Eligibility assessment and data extraction were performed by two reviewers. Data
      were assessed descriptively, and associations were tested by univariable and
      multivariable logistic regression. RESULTS: We identified 611 unique phase I
      cancer trials, of which 149 (24%) included an expansion cohort. The trials were
      significantly more likely to use an expansion cohort if they were published more
      recently, were multicenter, or evaluated a noncytotoxic agent. Objectives of the
      expansion cohort were reported in 74% of trials. In these trials, safety (80%),
      efficacy (45%), pharmacokinetics (28%), pharmacodynamics (23%), and patient
      enrichment (14%) were cited as objectives. Among expansion cohorts with safety
      objectives, the recommended phase II dose was modified in 13% and new toxicities
      were described in 54% of trials. Among trials aimed at assessing efficacy, only
      11% demonstrated antitumor activity assessed by response criteria that was not
      previously observed during dose escalation. CONCLUSION: The utilization of
      expansion cohorts has increased with time. Safety and efficacy are common
      objectives, but 26% fail to report explicit aims. Expansion cohorts may provide
      useful supplementary data for phase I trials, particularly with regard to
      toxicity and definition of recommended dose for phase II studies.

PMID- 24127442
TI  - Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in
      older patients with newly diagnosed acute myeloid leukemia: results of a
      randomized phase III trial by the EORTC and GIMEMA consortium (AML-17).
AB  - PURPOSE: This randomized trial evaluated the efficacy and toxicity of sequential
      gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly
      diagnosed acute myeloid leukemia (AML). PATIENTS AND METHODS: Patients (n = 472)
      age 61 to 75 years were randomly assigned to induction chemotherapy with
      mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6
      mg/m(2) on days 1 and 15). In remission, patients received two consolidation
      courses with or without GO (3 mg/m(2) on day 0). The primary end point was
      overall survival (OS). RESULTS: The overall response rate was comparable between
      the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were
      higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow
      up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no
      GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end
      points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities
      were greater in the GO arm. Treatment with GO provided no benefit in any
      prognostic subgroup, with the possible exception of patients age < 70 years with
      secondary AML, but outcomes were significantly worse in the oldest age subgroup
      because of a higher risk of early mortality. CONCLUSION: As used in this trial,
      the sequential combination of GO and standard chemotherapy provides no benefit
      for older patients with AML and is too toxic for those age >= 70 years.

PMID- 24127443
TI  - Tumor-infiltrating lymphocyte grade in primary melanomas is independently
      associated with melanoma-specific survival in the population-based genes,
      environment and melanoma study.
AB  - PURPOSE: Although most hospital-based studies suggest more favorable survival
      with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is
      uncertain whether TILs provide prognostic information beyond existing melanoma
      staging definitions. We addressed the issue in an international population-based
      study of patients with single and multiple primary melanomas. PATIENTS AND
      METHODS: On the basis of the Genes, Environment and Melanoma (GEM) study, we
      conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330
      invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or
      brisk). The odds of TIL grades associated with clinicopathologic features and
      survival by TIL grade were examined. RESULTS: Independent predictors (P < .05)
      for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and
      for brisk TIL grade, they were age, site, Breslow thickness, and radial growth
      phase. Nonbrisk and brisk TIL grades were each associated with lower American
      Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend)
      < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade
      (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade
      (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex,
      site, and AJCC tumor stage. CONCLUSION: At the population level, higher TIL grade
      of primary melanoma is associated with a lower risk of death as a result of
      melanoma independently of tumor characteristics currently used for AJCC tumor
      stage. We conclude that TIL grade deserves further prospective investigation to
      determine whether it should be included in future AJCC staging revisions.

PMID- 24127444
TI  - Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as
      first-line treatment of acute promyelocytic leukemia: a multicenter randomized
      controlled trial.
AB  - PURPOSE: This randomized, multicenter, phase III noninferiority trial was
      designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide
      (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF)
      compared with intravenous arsenic trioxide (ATO) as both induction and
      maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL).
      PATIENTS AND METHODS: In all, 242 patients with APL were randomly assigned (1:1)
      to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid
      (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission
      (CR), all patients received three courses of consolidation chemotherapy and
      maintenance treatment with sequential ATRA followed by either RIF or ATO for 2
      years. The primary end point was the rate of disease-free survival (DFS) at 2
      years, which was assessed for noninferiority with a 10% noninferiority margin.
      RESULTS: The median follow-up time was 39 months. DFS at 2 years was 98.1% (106
      of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS
      difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS
      difference was greater than the -10% noninferiority margin, confirming
      noninferiority (P < .001). No significant differences were noted between the RIF
      and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall
      survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were
      similar in the two groups. CONCLUSION: Oral RIF plus ATRA is not inferior to
      intravenous ATO plus ATRA as first-line treatment of APL and may be considered as
      a routine treatment option for appropriate patients.

PMID- 24127445
TI  - Restoring antitumor immunity via PD-1 blockade after autologous stem-cell
      transplantation for diffuse large B-cell lymphoma.

PMID- 24127446
TI  - Trastuzumab-related cardiotoxicity among older patients with breast cancer.
AB  - PURPOSE: The use of trastuzumab in the adjuvant setting improves outcomes but is
      associated with cardiotoxicity manifested as congestive heart failure (CHF). The
      rates and risk factors associated with trastuzumab-related CHF among older
      patients are unknown. PATIENTS AND METHODS: Breast cancer patients at least 66
      years old with full Medicare coverage, diagnosed with stage I-III breast cancer
      between 2005 and 2009, and treated with chemotherapy were identified in the SEER
      Medicare and in the Texas Cancer Registry-Medicare databases. The rates and risk
      factors associated with CHF were evaluated. Chemotherapy, trastuzumab use,
      comorbidities, and CHF were identified using International Classification of
      Diseases, version 9, and Healthcare Common Procedure Coding System codes.
      Analyses included descriptive statistics and Cox proportional hazards models.
      RESULTS: In total, 9,535 patients were included, of whom 2,203 (23.1%) received
      trastuzumab. Median age of the entire cohort was 71 years old. Among trastuzumab
      users, the rate of CHF was 29.4% compared with 18.9% in nontrastuzumab users (P <
      .001). Trastuzumab users were more likely to develop CHF than nontrastuzumab
      users (hazard ratio [HR], 1.95; 95% CI, 1.75 to 2.17). Among trastuzumab-treated
      patients, older age (age > 80 years; HR, 1.53; 95% CI, 1.16 to 2.10), coronary
      artery disease (HR, 1.82; 95% CI, 1.34 to 2.48), hypertension (HR, 1.24; 95% CI,
      1.02 to 1.50), and weekly trastuzumab administration (HR, 1.33; 95% CI, 1.05 to
      1.68) increased the risk of CHF. CONCLUSION: In this large cohort of older breast
      cancer patients, the rates of trastuzumb-related CHF are higher than those
      reported in clinical trials. Among patients treated with trastuzumab, those with
      cardiac comorbidities and older age may be at higher risk. Further studies need
      to confirm the role that the frequency of administration plays in the development
      of trastuzumab-related CHF.

PMID- 24127447
TI  - Level of HER2 gene amplification predicts response and overall survival in HER2
      positive advanced gastric cancer treated with trastuzumab.
AB  - PURPOSE: Previous studies have highlighted the importance of an appropriate human
      epidermal growth factor receptor 2 (HER2) evaluation for the proper
      identification of patients eligible for treatment with anti-HER2 targeted
      therapies. Today, the relationship remains unclear between the level of HER2
      amplification and the outcome of HER2-positive gastric cancer treated with first
      line chemotherapy with trastuzumab. The aim of this study was to determine
      whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio
      and HER2 gene copy number could significantly predict some benefit in overall
      survival and response to therapy in advanced gastric cancer treated with
      trastuzumab-based chemotherapy. PATIENTS AND METHODS: Ninety patients with
      metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy
      were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy
      number (GCN) for discriminating positive results in terms of response and
      prolonged survival were determined using receiver operating characteristic curves
      analyses. RESULTS: In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27
      to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80)
      were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff
      value discriminating sensitive and refractory patients (P = .005). Similarly, the
      optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005),
      and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the
      optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02).
      CONCLUSION: The level of HER2 gene amplification significantly predicts
      sensitivity to therapy and overall survival in advanced gastric cancer treated
      with trastuzumab-based chemotherapy.

PMID- 24127448
TI  - PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and
      pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients
      with platinum-resistant ovarian cancer.
AB  - PURPOSE: Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that
      binds to the folate receptor (FR), which is expressed on the majority of
      epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide
      combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The
      utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in
      selecting patients likely to benefit from vintafolide was also examined. PATIENTS
      AND METHODS: Women with recurrent platinum-resistant ovarian cancer who had
      undergone <= two prior cytotoxic regimens were randomly assigned at a 2:1 ratio
      to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without
      vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide
      scanning was optional. The primary objective was to compare progression-free
      survival (PFS) between the groups. RESULTS: The intent-to-treat population
      comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide
      plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41
      to 0.96; P = .031). The greatest benefit was observed in patients with 100% of
      lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD
      alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR
      positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873),
      whereas patients with disease that did not express FR experienced no PFS benefit
      (HR, 1.806). CONCLUSION: Vintafolide plus PLD is the first combination to
      demonstrate an improvement over standard therapy in a randomized trial of
      patients with platinum-resistant ovarian cancer. Etarfolatide can identify
      patients likely to benefit from vintafolide.

PMID- 24127449
TI  - Association between the prevalence of symptoms and health-related quality of life
      in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort
      study.
AB  - PURPOSE: We investigated the association between prevalence of symptoms and
      health-related quality of life (HRQOL) in adult survivors of childhood cancer
      enrolled in the St Jude Lifetime Cohort study. METHODS: Eligibility criteria
      include childhood malignancy treated at St Jude, survival >= 10 years from
      diagnosis, and current age >= 18 years. Study participants were 1,667 survivors
      (response rate = 65%). Symptoms were self-reported by using a comprehensive
      health questionnaire and categorized into 12 classes: cardiac; pulmonary;
      motor/movement; pain in head; pain in back/neck; pain involving sites other than
      head, neck, and back; sensation abnormalities; disfigurement; learning/memory;
      anxiety; depression; and somatization. HRQOL was measured by using
      physical/mental component summary (PCS/MCS) and six domain scores of the Medical
      Outcomes Study 36-Item Short-Form Health Survey. Multivariable regression
      analysis was performed to investigate associations between symptom classes and
      HRQOL. Cumulative prevalence of symptom classes in relation to time from
      diagnosis was estimated. RESULTS: Pain involving sites other than head, neck and
      back, and disfigurement represented the most frequent symptom classes, endorsed
      by 58.7% and 56.3% of survivors, respectively. Approximately 87% of survivors
      reported multiple symptom classes. Greater symptom prevalence was associated with
      poorer HRQOL. In multivariable analysis, symptom classes explained up to 60% of
      the variance in PCS and 56% of the variance in MCS; demographic and clinical
      variables explained up to 15% of the variance in PCS and 10% of the variance in
      MCS. Longer time since diagnosis was associated with higher cumulative prevalence
      in all symptom classes. CONCLUSION: A large proportion of survivors suffered from
      many symptom classes, which was associated with HRQOL impairment.

PMID- 24127450
TI  - Delivering high-quality and affordable care throughout the cancer care continuum.
AB  - The national cost of cancer care is projected to reach $173 billion by 2020,
      increasing from $125 billion in 2010. This steep upward cost trajectory has
      placed enormous an financial burden on patients, their families, and society as a
      whole and raised major concern about the ability of the health care system to
      provide and sustain high-quality cancer care. To better understand the cost
      drivers of cancer care and explore approaches that will mitigate the problem, the
      National Cancer Policy Forum of the Institute of Medicine held a workshop
      entitled "Delivering Affordable Cancer Care in the 21st Century" in October 2012.
      Workshop participants included bioethicists, health economists, primary care
      physicians, and medical, surgical, and radiation oncologists, from both academic
      and community settings. All speakers expressed a sense of urgency about the
      affordability of cancer care resulting from the future demographic trend as well
      as the high cost of emerging cancer therapies and rapid diffusion of new
      technologies in the absence to evidence indicating improved outcomes for
      patients. This article is our summary of presentations at the workshop that
      highlighted the overuse and underuse of screening, treatments, and technologies
      throughout the cancer care continuum in oncology practice in the United States. 

PMID- 24127451
TI  - Lapatinib versus placebo added to paclitaxel in first-line human epidermal growth
      factor receptor 2-positive metastatic breast cancer: ethical lessons not learned
      from Africa.

PMID- 24127453
TI  - Reply to F. Ades.

PMID- 24127452
TI  - Disabling immune tolerance by programmed death-1 blockade with pidilizumab after
      autologous hematopoietic stem-cell transplantation for diffuse large B-cell
      lymphoma: results of an international phase II trial.
AB  - PURPOSE: The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped
      by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune
      surveillance. The reconstituting immune landscape after autologous hematopoietic
      stem-cell transplantation (AHSCT) may be particularly favorable for breaking
      immune tolerance through PD-1 blockade. PATIENTS AND METHODS: We conducted an
      international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in
      patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte
      subsets. Patients received three doses of pidilizumab beginning 1 to 3 months
      after AHSCT. RESULTS: Sixty-six eligible patients were treated. Toxicity was
      mild. At 16 months after the first treatment, progression-free survival (PFS) was
      0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high
      risk patients who remained positive on positron emission tomography after salvage
      chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35
      patients with measurable disease after AHSCT, the overall response rate after
      pidilizumab treatment was 51%. Treatment was associated with increases in
      circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting
      an on-target in vivo effect of pidilizumab. CONCLUSION: This is the first
      demonstration of clinical activity of PD-1 blockade in DLBCL. Given these
      results, PD-1 blockade after AHSCT using pidilizumab may represent a promising
      therapeutic strategy in this disease.

PMID- 24127456
TI  - Electrochemotherapy with intravenous bleomycin injection: an observational study
      in superficial squamous cell carcinoma in cats.
AB  - The aim of this study was to evaluate the efficacy and safety of
      electrochemotherapy (ECT) with bleomycin for treatment of squamous cell carcinoma
      (SCC) in cats. Between March 2008 and October 2011, 11 cats with 17 superficial
      SCC nodules in different clinical stages (ranging from Tis to T4), located on
      nasal planum (6/11), pinnae (3/11) and both locations (2/11), were included in a
      prospective non-randomised study. Sixteen of 17 SCC nodules were treated with ECT
      (15/16 with single session and in one case with two sessions); one nodule was
      surgically removed. Altogether, complete response (CR) was achieved for 81.8%
      (9/11) cats and 87.5% (14/16) nodules, lasting from 2 months up to longer than 3
      years. Only 2/9 cats in which CR was initially observed, had recurrence 2 and 8
      months after the ECT procedure. In the remaining two cats with highly
      infiltrative spread into adjacent tissues, progression of the disease was
      observed, despite ECT, and both were euthanased 4 and 5 months after the
      procedure. ECT in cats was well tolerated and no evident local or systemic side
      effects were observed. The results of this study suggest that ECT is a highly
      effective and safe method of local tumour control of feline cutaneous SCCs. It
      should be considered as an alternative treatment option, especially when other
      treatment approaches are not acceptable by the owners, owing to their
      invasiveness, mutilation or high cost. 

PMID- 24127454
TI  - Hematopoietic cell transplantation-specific comorbidity index predicts inpatient
      mortality and survival in patients who received allogeneic transplantation
      admitted to the intensive care unit.
AB  - PURPOSE: To investigate the prognostic value of the Hematopoietic Cell
      Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received
      transplantation admitted to the intensive care unit (ICU). PATIENTS AND METHODS:
      We investigated the association of HCT-CI with inpatient mortality and overall
      survival (OS) among 377 patients who were admitted to the ICU within 100 days of
      allogeneic stem-cell transplantation (ASCT) at our institution. HCT-CI scores
      were collapsed into four groups and were evaluated in univariate and multivariate
      analyses using logistic regression and Cox proportional hazards models. RESULTS:
      The most common pretransplantation comorbidities were pulmonary and cardiac
      diseases, and respiratory failure was the primary reason for ICU admission. We
      observed a strong trend for higher inpatient mortality and shorter OS among
      patients with HCT-CI values >= 2 compared with patients with values of 0 to 1 in
      all patient subsets studied. Multivariate analysis showed that patients with HCT
      CI values >= 2 had significantly higher inpatient mortality than patients with
      values of 0 to 1 and that HCT-CI values >= 4 were significantly associated with
      shorter OS compared with values of 0 to 1 (hazard ratio, 1.74; 95% CI, 1.23 to
      2.47). The factors associated with lower inpatient mortality were ICU admission
      during the ASCT conditioning phase or the use of reduced-intensity conditioning
      regimens. The overall inpatient mortality rate was 64%, and the 1-year OS rate
      was 15%. Among patients with HCT-CI scores of 0 to 1, 2, 3, and >= 4, the 1-year
      OS rates were 22%, 17%, 18%, and 9%, respectively. CONCLUSION: HCT-CI is a
      valuable predictor of mortality and survival in critically ill patients after
      ASCT.

PMID- 24127457
TI  - Ejaculation training, seminal alkaline phosphatase and semen preservation through
      cooling in a milk-based extender in domestic cats.
AB  - The purpose of this report is to describe (1) the training of domestic cats in
      ejaculation into an artificial vagina (AV), (2) alkaline phosphatase (AP)
      concentrations in whole ejaculates, and (3) the in vitro effect of a skimmed-milk
      plus egg yolk (SM-Y) extender on feline spermatozoa incubated at 4oC. Five post
      pubertal cats were trained to ejaculate into an AV three times a week for 20 mins
      in the presence of a teaser queen. Fifty AV-obtained ejaculates were macro- and
      microscopically assessed, and the AP therein measured by optimized colorimetry.
      Eighty AV-obtained ejaculates were pooled, diluted in SM-Y extender [80% (v/v)
      skimmed milk, 20% (v/v) egg yolk, and antibiotics], stored at 4 degrees C and
      evaluated daily for 6 days. All the animals could be trained to ejaculate,
      although the interval up to the first AV ejaculation varied from 1.5 to 5.5
      months (mean 3.9 months). The final performance at collection ranged from
      excellent to poor and was inversely related to the training period required in
      all cases. The mean AP concentration in whole ejaculates was 20,645.6 +/-
      4405U/l, which was not correlated with the concentration of spermatozoa. Most
      seminal parameters [(%); total (77 +/- 2.3) and progressive (62.7 +/- 3.4)
      motility, live sperm (91.8 +/- 1.2), intact plasmalemma (83.5 +/- 2.6), normal
      acrosomes (83.5 +/- 2.6), pH (6.6 +/- 0.0) and osmolarity (mOsm/l; 321 +/- 5.2)],
      though decreasing during storage in the cold, remained within values compatible
      with in vivo fertilization for 2 days. 

PMID- 24127458
TI  - Detection of serum antibodies against Bartonella species in cats with
      sporotrichosis from Rio de Janeiro, Brazil.
AB  - Cat scratch disease is a zoonosis caused by Bartonella species, transmitted to
      humans through scratches or bites from infected cats and via direct contact with
      infected feces. Sporotrichosis, caused by the fungal complex Sporothrix, is
      transmitted by traumatic inoculation of the fungus. Cats are important in
      zoonotic transmission. Serum samples from 112 domestic cats with sporotrichosis
      and 77 samples from healthy cats were analyzed by indirect immunofluorescence
      assay (IFA), using the commercial kit Bartonella henselae IFA IgG (Bion). The
      presence of antibodies against feline leukemia virus (FeLV) and of feline
      immunodeficiency virus (FIV) core antigens was detected using the commercial kit
      Snap Combo FIV-FeLV (Idexx). The group of animals with sporotrichosis contained
      93 males with a median age of 22 months, eight (7.1%) of which were positive for
      FIV and 15 (13.4%) for FeLV. The group of animals without sporotrichosis
      contained 36 males with a median age 48 months, 10 (13.0%) of which were positive
      for FIV and eight (10.4%) for FeLV. Of the 112 cats with sporotrichosis and 77
      cats without mycosis, 72 (64.3%) and 35 (45.5%), respectively, were IFA reactive.
      No association was found between age, sex, FIV/FeLV and the presence of
      antibodies to Bartonella species. The results suggest that the study population
      can be considered a potential source of zoonotic infection for both diseases. 

PMID- 24127459
TI  - Aging in Sweden: local variation, local control.
AB  - Aging in Sweden has been uniquely shaped by its history-most notably the long
      tradition of locally controlled services for older adults. We considered how
      local variations and local control shape the experience of aging in Sweden and
      organized the paper into 3 sections. First, we examine aging in Sweden along
      demography, economy, and housing. Next, we trace the origins and development of
      the Swedish welfare state to consider formal supports (service provision) and
      informal supports (caregiving and receipt of care). Finally, we direct
      researchers to additional data resources for understanding aging in Sweden in
      greater depth. Sweden was one of the first countries to experience rapid
      population aging. Quality of life for a majority of older Swedes is high. Local
      control permits a flexible and adaptive set of services and programs, where
      emphasis is placed on improving the quality and targeting of services that have
      already reached a plateau as a function of population and expenditures. 

PMID- 24127461
TI  - Condylar fractures of the proximal and middle phalanges.
AB  - We describe the treatment of 74 patients with phalangeal condylar fractures.
      Twelve patients presenting with undisplaced fractures were initially treated
      nonoperatively; of these, five displaced, requiring fixation. The remaining seven
      patients, all children, united uneventfully. Sixty-two patients presenting with
      displaced fractures were treated with internal fixation using a single lag screw
      through a lateral approach. The patients were treated semi-electively on a day
      surgery unit. Twenty-seven patients with unicondylar fractures, all operated on
      within 2 weeks of injury, regained full range of movement. Thirty-eight patients
      had loss of extension (range 10-35 degrees ) with fixed flexion contractures at
      the proximal interphalangeal and thumb interphalangeal joints and extensor lag at
      the distal interphalangeal joints (overall mean extension loss 10 degrees ).
      Although fixation was technically easier during the first week, a delay of 2
      weeks before fixation made little difference to the outcome. In our experience,
      fractures can be taken down and fixed internally even 8 weeks after injury. If
      nonoperative treatment is initially embarked upon, close monitoring is required
      with weekly radiographs up to 3 weeks, as these fractures will frequently
      displace. 

PMID- 24127462
TI  - Surgical technique for management of symptomatic digital clubbing.

PMID- 24127463
TI  - A prospective case-control study to compare the sensitivity and specificity of
      the grind and traction-shift (subluxation-relocation) clinical tests in
      osteoarthritis of the thumb carpometacarpal joint.
AB  - The diagnosis of osteoarthritis of the thumb carpometacarpal joint is made
      predominantly by correlating examination findings with patients' symptoms and
      radiographs. The importance of clinical examination is enhanced due to the poor
      correlation between radiological severity of osteoarthritis of this joint and
      symptoms. Despite the importance of clinical examination findings, no previous
      studies have analyzed the traction-shift test nor compared clinical tests for
      this diagnosis. In this prospective case-control study the relative performance
      of the commonly used grind and traction-shift (subluxation-relocation) tests were
      compared in 30 patients and 30 unaffected controls. The traction-shift test had
      greater sensitivity (66.7%) and specificity (100%) than the grind test (30% and
      96.7%, respectively), whilst also demonstrating superior positive (100%) and
      negative (75%) predictive value than the grind test (90% and 58%, respectively).
      Therefore, we believe this to be the superior clinical test for osteoarthritis of
      the carpometacarpal joint of the thumb. 

PMID- 24127464
TI  - Isolated second toe transfer after total amputation of the left fifth finger in a
      professional guitar player.

PMID- 24127465
TI  - Contact areas of the scaphoid and lunate with the distal radius in neutral and
      extension: correlation of falling strategies and distal radial anatomy.
AB  - The functional neutral of wrist movement is about 10 degrees  extension yet the
      distal radius has a volar tilt. This has not previously been explained. Assuming
      that the contact area between the carpus and the distal radius increased in wrist
      extension this would also help stabilize the carpus on the distal radius in
      positions where typically there is greater loading. To test this hypothesis we
      reconstructed three-dimensional structures of the carpal bones and distal radius
      using computed tomography scans of 13 normal wrists. The contact areas of the
      scaphoid with the distal radius were measured and were found progressively
      increased from flexion 20 degrees , neutral, extension 20 degrees , to extension
      40 degrees . The maximal increases in the contact area of the scaphoid and the
      distal radius was at full wrist extension. No significant changes in the contact
      areas of the lunate with the distal radius were found between the different
      positions. The contact characteristics provide greater stability to the carpus on
      the distal radius, and to help spread forces from impact to the wrist reducing
      the transmitted peak forces and thus the risk of distal radius and carpal
      injuries. 

PMID- 24127467
TI  - Cognitive behavior therapy for pediatric functional abdominal pain: a randomized
      controlled trial.
AB  - OBJECTIVE: This randomized controlled trial investigated the effectiveness of a 6
      session protocolized cognitive behavior therapy (CBT) compared with 6 visits to a
      pediatrician (intensive medical care; IMC) for the treatment of pediatric
      functional abdominal pain (FAP). METHODS: One hundred four children aged 7 to 18
      were randomized to CBT or IMC. CBT was delivered primarily by trained master's
      degree students in psychology; IMC was delivered by pediatricians or pediatric
      gastroenterologists. Assessments were performed pretreatment, posttreatment, and
      at 6- and 12-month follow-up. Primary outcomes were level of abdominal pain (AP)
      as reported on questionnaires and diaries. Secondary outcomes were other
      gastrointestinal complaints, functional disability, other somatic complaints,
      anxiety, depression, and quality of life. RESULTS: Both CBT and IMC resulted in a
      significant decrease in AP (P < .001), but no significant difference was found
      between the treatments in their effectiveness (P > .05 for all end points).
      According to the questionnaire-derived data, 1 year after treatment, 60% of
      children that received CBT had significantly improved or recovered, versus 56.4%
      of children receiving IMC, which did not significantly differ (P = .47). These
      percentages were 65.8% versus 62.8% according to the diary-derived data, which
      also did not significantly differ (P = .14). Additionally, nearly all secondary
      outcomes improved after treatment. CONCLUSIONS: CBT was equally effective as IMC
      in reducing AP in children with FAP. More research into the specific working
      mechanisms of CBT for pediatric FAP is needed.

PMID- 24127466
TI  - Complementary and conventional medicine use among youth with recurrent headaches.
AB  - OBJECTIVE: To identify prevalence and patterns of complementary and alternative
      medicine (CAM) use among youth with recurrent headaches (HA) and evaluate
      associations with co-occurring health problems and limitations as well as with
      the use and expenditures for conventional medical care. METHODS: Variables were
      constructed for youth aged 10 to 17 by using linked data from the 2007 National
      Health Interview Survey and the 2008 Medical Expenditures Panel Survey.
      Bivariate, logistic, and 2-part regression analyses were used. RESULTS: Of the
      10.6% of youth experiencing HA, 29.6% used CAM, rising to 41% for the many HA
      sufferers who also experienced difficulties with emotions, concentration,
      behavior, school attendance, or daily activities. Biologically based products
      (16.2%) and mind-body therapies (13.3%) were most commonly used, especially by
      the 86.4% of youth with HA experiencing at least 1 other chronic condition.
      Compared with non-CAM users, youth with HA who used CAM also had higher
      expenditures for and use of most types of conventional care. CONCLUSIONS: CAM use
      is most common among youth with HA experiencing multiple chronic conditions and
      difficulties in daily functioning. Associations among CAM use, multiple chronic
      conditions, and higher use of conventional care highlight the need for medical
      providers to routinely ask about CAM use to meet the complex health needs of
      their patients and facilitate the optimal integration of care. Research is needed
      to identify models for coordinating complementary and conventional care within a
      medical home and to understand the health benefits or risks associated with CAM
      use in conjunction with conventional treatments for patients with HA.

PMID- 24127468
TI  - End-stage kidney disease after pediatric nonrenal solid organ transplantation.
AB  - OBJECTIVES: Adult solid organ transplant (SOT) recipients commonly develop
      advanced kidney disease; however, the burden of end-stage kidney disease (ESKD)
      in children after SOT is not well-described. The objectives of this study were to
      determine the incidence of ESKD after pediatric SOT and the relative risk by SOT
      type. METHODS: Retrospective multicenter cohort study of children, ages <= 18
      years, who received SOTs from 1990 through 2010 using Scientific Registry of
      Transplant Recipients data linked to the US Renal Data System. We performed a
      competing risks analysis to determine cumulative incidence of ESKD (chronic
      dialysis or kidney transplant), treating death as a competing risk, and fit a
      multivariable Cox regression model to assess hazard of ESKD by organ type.
      RESULTS: The cohort included 16,604 pediatric SOT recipients (54% liver, 34%
      heart, 6% lung, 6% intestine, and 1% heart-lung). During a median follow-up of
      6.2 years (interquartile range 2.2-12.1), 426 (3%) children developed ESKD.
      Compared with liver transplant recipients, in whom the incidence of ESKD was 2.1
      cases per 1000 person-years, in adjusted analyses the highest risk of ESKD was
      among intestinal (hazard ratio [HR] 7.37, P < .001), followed by lung (HR 5.79, P
      < .001) and heart transplant recipients (HR 1.79, P < .001). CONCLUSIONS: In a 20
      year national cohort of pediatric SOT recipients, the risk of ESKD was highest
      among intestinal and lung transplant recipients. The burden of earlier stages of
      chronic kidney disease is probably much higher; modifiable risk factors should be
      targeted to prevent progressive kidney damage in this high-risk population.

PMID- 24127469
TI  - Off-label topical calcineurin inhibitor use in children.
AB  - OBJECTIVE: To assess off-label use of the topical calcineurin inhibitors (TCIs),
      tacrolimus and pimecrolimus, in children during periods before and after
      regulatory action by the US Food and Drug Administration (FDA) in 2005. METHODS:
      We identified new pediatric (age <20 years) users of topical tacrolimus or
      pimecrolimus in US Medicaid from 2001 to 2009, and examined the annual rate of
      drug use (pre- and postregulatory action) by age. We assessed medical claims for
      diagnoses consistent with an indication for a TCI, and assessed prescriptions for
      evidence of first-line atopic dermatitis therapy use before TCI initiation.
      RESULTS: There were 57,664 eligible pediatric tacrolimus users and 425,242
      eligible pediatric pimecrolimus users at baseline. The rate of TCI use decreased
      substantially after FDA regulatory action. The proportion of new users younger
      than 2 years of age significantly decreased for both tacrolimus (36.7% to 22.5%,
      P < .001) and pimecrolimus (47.0% to 33.7%, P < .001) after regulatory actions.
      Previous use of topical corticosteroids increased by ~ 7% for both TCIs from the
      pre- to postregulatory period. However, after regulatory actions, there was only
      a small increase in the proportion of tacrolimus or pimecrolimus users with an
      atopic dermatitis or eczema diagnosis before drug initiation, and high strength
      use of tacrolimus was unchanged. CONCLUSIONS: The rate of TCI use in children
      younger than 2 years of age fell substantially after FDA regulatory action in
      2005. Off-label use of TCI as first-line therapy changed little.

PMID- 24127470
TI  - Physical activity in children attending preschools.
AB  - OBJECTIVE: To identify correlates of objectively measured moderate and vigorous
      physical activity (MVPA) in children during preschool attendance. METHODS: This
      cross-sectional study included data from 426 apparently healthy Danish children
      (49.5% boys), 5 to 6 years of age enrolled in 42 randomly selected preschools.
      The percentage of time spent in MVPA (>= 574 counts/15 second) during preschool
      attendance was measured using ActiGraph accelerometers over 4.3 preschool days in
      May and June in 2009. Thirty-seven potential correlates across the child,
      preschool staff, and preschool environment domains were tested for associations
      with MVPA. RESULTS: The final multivariate model identified 9 significant
      correlates of MVPA. Preterm birth, vegetation on the playground, and rainy days
      were negatively associated with MVPA, whereas child motor coordination, location
      of preschool building on the playground, gender (boys), percentage afternoon
      hours, and size of indoor area per child were positively associated with MVPA.
      The direction of the significant association with the parental mean education
      level was unclear. CONCLUSIONS: We identified a number of new modifiable
      correlates of MVPA during preschool attendance. The positive association with
      size of indoor area per child and location of the preschool building on the
      playground seem important correlates to be targeted in future studies.

PMID- 24127471
TI  - Changes in bedtime schedules and behavioral difficulties in 7 year old children.
AB  - OBJECTIVES: Causal links between disrupted sleep and behavioral problems in
      nonclinical populations are far from clear. Research questions were as follows:
      Are bedtime schedules associated with behavioral difficulties? Do effects of
      bedtime schedules on behavior build up over early childhood? Are changes in
      bedtime schedules linked to changes in behavior? METHODS: Data from 10,230 7-year
      olds from the UK Millennium Cohort Study, with bedtime data collected at 3, 5,
      and 7 years, and behavioral difficulties scores as rated by mothers and teachers
      were analyzed. RESULTS: Children with nonregular bedtimes had more behavioral
      difficulties. There was an incremental worsening in behavioral scores as exposure
      through early childhood to not having regular bedtimes increased: mother rated
      (nonregular any 1 age, beta = 0.53; nonregular any 2 ages, beta = 1.04;
      nonregular all 3 ages, beta = 2.10, P < .001) and teacher rated (beta = 0.22,
      beta = 0.73, beta = 1.85, P < .001). Difference in differences analysis showed
      that for children who changed from nonregular to regular bedtimes there were
      clear nontrivial, statistically significant improvements in behavioral scores: A
      change between age 3 and 7 corresponded to a difference of beta = -0.63, and a
      change between age 5 and 7 corresponded to a difference of beta = -1.02). For
      children who changed from regular to nonregular bedtimes between ages 5 and 7
      there was a statistically significant worsening in scores, beta = 0.42.
      CONCLUSIONS: Having regular bedtimes during early childhood is an important
      influence on children's behavior. There are clear opportunities for interventions
      aimed at supporting family routines that could have important impacts on health
      throughout life.

PMID- 24127472
TI  - Reliability of transcutaneous bilirubin devices in preterm infants: a systematic
      review.
AB  - BACKGROUND AND OBJECTIVE: Transcutaneous bilirubin (TcB) devices are widely used
      for the estimation of serum bilirubin levels in term and near-term infants. Our
      objective was to review the diagnostic accuracy of TcB devices in preterm
      infants. METHODS: Medline, Embase, Cochrane library, Cumulative Index to Nursing
      and Allied Health Literature, and Scopus were searched (from database inception
      date until December 2012). Additional citations were identified by using the
      bibliographies of selected articles and from conference proceedings. The studies
      were included if they compared TcB with total serum bilirubin in preterm infants
      before phototherapy and presented data as correlation coefficients or as Bland
      Altman difference plots. Data were extracted by 1 reviewer and checked for
      accuracy by the second reviewer. An assessment tool (quality assessment of
      diagnostic accuracy studies) was used for risk of bias assessments. RESULTS:
      Twenty-two studies met the inclusion criteria; 21 studies reported results as
      correlation coefficients, with pooled estimates of r = 0.83 for each site of
      measurement. Pooled estimates in infants <32 weeks' gestation were similar to the
      overall preterm population (r = 0.89 [95% confidence interval: 0.82-0.93]). For
      the 2 commonly used TcB devices (ie, JM103 and BiliCheck), the results were
      comparable at the forehead site, although the JM103 device exhibited better
      correlation at the sternum. Analysis of the Bland-Altman plots (13 studies)
      revealed negligible bias in measurement at the forehead or sternum site by using
      either the JM-103 or BiliCheck device; however, the JM-103 device exhibited
      better precision than the BiliCheck (SD for TcB - total serum bilirubin
      differences: 24.3 and 31.98 umol/L, respectively). CONCLUSIONS: The TcB devices
      reliably estimated bilirubin levels in preterm infants and could be used in
      clinical practice to reduce blood sampling.

PMID- 24127473
TI  - Higher-hazard, no benefit research involving children: parental perspectives.
AB  - OBJECTIVES: US regulations allow local institutional review boards to approve
      greater than minimal risk, no-benefit research when the research enrolls children
      with the condition under study but not when it enrolls healthy children. We aim
      to describe the opinions of parents regarding higher-hazard, no-benefit research
      METHODS: Quantitative and qualitative interviews with parents of children without
      heart disease or chronic medical conditions (no heart disease [noHD], n = 30),
      children with fully correctable heart disease (FCHD, n = 30), and children with
      life-altering heart disease (LAHD, n = 30). RESULTS: Parents of children with
      heart disease endorse higher-hazard, no-benefit heart disease research more
      strongly than noHD parents. Eight of 30 noHD parents, 19 of 30 FCHD parents, and
      26 of 30 LAHD parents reported willingness to enroll their children in a heart
      disease research study involving an otherwise unnecessary chest radiograph (P <
      .01). There was no difference among groups in willingness to enroll their
      children in a similar study focused on childhood cancer. Twenty-two of 30 FCHD
      and 30 of 30 LAHD parents reported that parents have a responsibility to enroll
      their children in medical research to help future children with heart disease.
      Twenty-one of 30 noHD parents, 29 of 30 FCHD parents, and 30 of 30 LAHD parents
      feel able to evaluate the risks of medical research (P = .01). CONCLUSIONS:
      Parental opinions regarding higher-hazard, no-benefit research align with federal
      regulations. Parental willingness to enroll their children in higher-hazard, no
      benefit research is driven in part by a sense of obligation to a community of
      families affected by childhood heart disease.

PMID- 24127474
TI  - Nocardia brasiliensis infection mimicking juvenile idiopathic arthritis in a 4
      year-old girl.
AB  - Nocardia are ubiquitous environmental saprophytes that cause pneumonia and
      disseminated disease in immunocompromised patients. They can also cause localized
      cutaneous and soft tissue infections in healthy people after direct percutaneous
      inoculation. Nocardia arthritis is rare in both forms of the disease. Here we
      present the first published case of a child with septic arthritis caused by N
      brasiliensis. Importantly, this otherwise well 4-year-old girl had no known
      history of trauma but presented with transient cutaneous lesions and a 6-week
      history of arthritis involving the right fourth digit proximal interphalangeal
      joint without accompanying fever or raised systemic inflammatory markers. She
      received a diagnosis of juvenile idiopathic arthritis and underwent
      antiinflammatory and immunosuppressant therapy. After 2 months she developed
      frank septic arthritis, which necessitated a surgical joint washout, from which
      an intraoperative swab grew N brasiliensis. The patient received 6 months of high
      dose trimethoprim-sulfamethoxazole and remains well more than 4 years after
      treatment. This unusual case highlights the importance of considering an indolent
      infection from slow-growing organisms, including Nocardia, when diagnosing the
      oligoarthritis subtype of juvenile idiopathic arthritis. This is especially
      relevant when a single joint is involved and response to antiinflammatory therapy
      is suboptimal because antiinflammatory agents may mask evolving signs of
      infection. 

PMID- 24127475
TI  - Rare bleeding disorders in children: identification and primary care management.
AB  - Bleeding symptoms are common in healthy children but occasionally may indicate an
      underlying congenital or acquired bleeding diathesis. The rare bleeding disorders
      (RBDs) comprise inherited deficiencies of coagulation factors I (congenital
      fibrinogen deficiencies), II, V, VII, X, XI, and XIII and combined factor
      deficiencies, most notably of factors V and VIII and of vitamin K-dependent
      factors. These disorders often manifest during childhood and may present with
      recurrent or even serious or life-threatening bleeding episodes, particularly
      during the neonatal period. Accordingly, primary care and other nonhematologist
      pediatric providers should be familiar with the clinical presentation and initial
      evaluation of these rare disorders. Bleeding manifestations generally vary within
      the same RBD and may be indistinguishable from 1 RBD to another or from other
      more common bleeding disorders. Serious bleeding events such as intracranial
      hemorrhage may be heralded by less serious bleeding symptoms. The results of
      initial coagulation studies, especially prothrombin time and activated partial
      thromboplastin time, are often helpful in narrowing down the potential factor
      deficiency, with factor XIII deficiency being an exception. Consultation with a
      hematologist is advised to facilitate accurate diagnosis and to ensure proper
      management and follow-up. The approach to bleeding episodes and invasive
      procedures is individualized and depends on the severity, frequency, and, in the
      case of procedures, likelihood of bleeding. Prophylaxis may be appropriate in
      children with recurrent serious bleeding and specifically after life-threatening
      bleeding episodes. When available, specific purified plasma-derived or
      recombinant factor concentrates, rather than fresh frozen plasma or
      cryoprecipitate, are the treatment of choice. 

PMID- 24127476
TI  - Pulmonary capillaritis in monozygotic twin boys.
AB  - Pulmonary hemorrhage can be classified as either proximal or distal (alveolar).
      Causes of proximal hemorrhage include infection, foreign body aspiration,
      pulmonary embolus, trauma, vascular malformation, and pulmonary hypertension.
      Causes of distal or diffuse alveolar hemorrhage are divided by the histologic
      presence or absence of capillaritis, which is characterized by inflammation of
      the alveolar interstitium and pulmonary capillary structure. Pulmonary
      capillaritis is a rare event in children and is associated with higher morbidity
      and mortality than diffuse alveolar hemorrhage without capillaritis. This is a
      report of 17-month-old previously healthy monozygotic twins presenting
      simultaneously with diffuse alveolar hemorrhage, pulmonary capillaritis, and an
      otherwise negative serologic workup. This suggests a role of genetic
      predisposition in this rare disease. 

PMID- 24127477
TI  - The Red Book through the ages.
AB  - The first edition of the Red Book was published in 1938. Since then, there have
      been numerous advances in the fields of infectious diseases and public health
      that have decreased morbidity and mortality of infants, children, and
      adolescents. Over the years, emerging pathogens and disease complexes have been
      described, sophisticated diagnostic techniques developed, advances in
      antimicrobial therapy have occurred, and immunizations have been implemented to
      prevent previously deadly diseases. Of the 18 diseases or organisms in the 1938
      edition, 13 are now vaccine-preventable. Since inception of the Red Book, the
      aims of the editors have been to keep pace with these innovations and to continue
      to inform the medical community. These goals have made the Red Book a fundamental
      resource for pediatricians and other health care professionals in terms of
      guiding diagnosis, therapy, and prevention of infectious diseases. The list of 18
      diseases or organisms originally described in the 1938 Red Book has expanded to
      include over 160 diseases or organisms in the 2012 edition. The pace of
      biomedical discovery, as well as the amount of information available and the
      number of methods for its delivery, will continue to accelerate in the future.
      Integration of information into future editions of the Red Book will ensure that
      practitioners continue to rely on the Red Book in its various electronic formats
      for clinical guidance and support. 

PMID- 24127478
TI  - RSV immunoprophylaxis: does the benefit justify the cost?

PMID- 24127479
TI  - Effect of palivizumab prophylaxis on subsequent recurrent wheezing in preterm
      infants.
AB  - BACKGROUND AND OBJECTIVES: Palivizumab effectively prevents severe respiratory
      syncytial virus (RSV) disease in preterm infants. Our objective was to test
      whether palivizumab prophylaxis given to preterm infants during the first RSV
      season reduces the incidence of subsequent recurrent wheezing up to 3 years of
      life. METHODS: We conducted an observational prospective multicenter (52
      registered hospitals in Japan) case-control study in preterm infants with a
      gestational age between 33 and 35 weeks followed for 3 years. During the 2007
      2008 RSV season, the decision to administer palivizumab was made based on
      standard medical practice. In April 2008, 52 hospitals were recruited. Study
      participants were prospectively followed to the age of 3 years. Parents of study
      subjects reported the infants' physician's assessment of recurrent wheezing, used
      a report card and a novel mobile phone-based reporting system by using the
      Internet. The primary end point was the incidence of physician-diagnosed
      recurrent wheezing. RESULTS: Of 444 preterm infants enrolled, 349 received
      palivizumab during the first 6 months of life and 95 infants did not. Physician
      diagnosed recurrent wheezing was observed in 6.4% and 18.9% of infants in the
      treated and untreated groups, respectively (P < .001). This difference remained
      significant after adjustment for known risk factors of recurrent wheezing (P <
      .001). CONCLUSIONS: Palivizumab prophylaxis administered to preterm infants 33 to
      35 weeks' gestational age is associated with a significantly lower incidence of
      recurrent wheezing during the first 3 years of life.

PMID- 24127480
TI  - Improving depression screening for adolescents with type 1 diabetes.
AB  - OBJECTIVE: Depression is common among adolescents, but rates increase
      significantly in the presence of chronic health conditions. Outpatient screening
      for depression is recommended but rarely formally conducted due to barriers of
      implementation. METHODS: To provide a model for depression screening of youth
      with chronic health conditions, a standard process using a self-administered
      electronic version of the Children's Depression Inventory (CDI) was developed.
      Quality improvement methodology and traditional analytic approaches were used to
      test the feasibility and outcomes of routine screening in patients 13 to 17 years
      of age with type 1 diabetes. RESULTS: Of the 528 eligible adolescents, 509 (96%)
      received at least 1 depression screen during the first year. The process was
      tested and refined in over 1200 patient encounters, which resulted in an increase
      in depression screening rates from <5% to a median of 85% over the initial 12
      months. Both patients and staff reported acceptance of screening on qualitative
      surveys. Elevated CDI scores (>= 16) were found in 8% of the sample; moderate
      scores (10-15) in 12% of the sample. Low risk scores were found in 80% of the
      sample. Higher CDI scores correlated with lower blood glucose monitoring
      frequency and higher hemoglobin A1c, confirming the link between more depression
      symptoms and poorer diabetes management and control. Suicidal ideation was
      endorsed in 7% of the population. CONCLUSIONS: Systematic depression screening in
      adolescents with type 1 diabetes can be reliably implemented with clinically
      significant results. A systematic approach, such as described in this study, can
      serve as a model for other chronic health conditions.

PMID- 24127482
TI  - How university students with reading difficulties are supported in achieving
      their goals.
AB  - We examine (a) what social ties university students with a history of reading
      difficulty (RD) report assisting them to achieve their goals, (b) outlets
      available for developing social ties, (c) resources mobilized within these
      relationships, and (d) the impact of social ties' status on academic achievement.
      Participants were 107 university students with RD who were currently completing
      or had recently completed a university degree. Results showed that university
      students with RD named friends, parents, and significant others (e.g.,
      boy/girlfriend, spouse) as social ties most often. Personal social ties were
      developed through social media networking sites and within close relationships,
      and institutional social ties through academic centers and university general
      services, among others. Resources mobilized among personal and institutional
      social ties included emotional and social support, advice and planning, writing
      and studying help, and goal setting. Institutional social ties also afforded job
      search assistance, accommodations, skill development, financial support, and
      mental health services. Finally, the status of employed, but not student, social
      ties explained academic achievement. 

PMID- 24127481
TI  - Gunshot injuries in children served by emergency services.
AB  - OBJECTIVE: To describe the incidence, injury severity, resource use, mortality,
      and costs for children with gunshot injuries, compared with other injury
      mechanisms. METHODS: This was a population-based, retrospective cohort study
      (January 1, 2006-December 31, 2008) including all injured children age <= 19
      years with a 9-1-1 response from 47 emergency medical services agencies
      transporting to 93 hospitals in 5 regions of the western United States. Outcomes
      included population-adjusted incidence, injury severity score >= 16, major
      surgery, blood transfusion, mortality, and average per-patient acute care costs.
      RESULTS: A total of 49,983 injured children had a 9-1-1 emergency medical
      services response, including 505 (1.0%) with gunshot injuries (83.2% age 15-19
      years, 84.5% male). The population-adjusted annual incidence of gunshot injuries
      was 7.5 cases/100,000 children, which varied 16-fold between regions. Compared
      with children who had other mechanisms of injury, those injured by gunshot had
      the highest proportion of serious injuries (23%, 95% confidence interval [CI]
      17.6-28.4), major surgery (32%, 95% CI 26.1-38.5), in-hospital mortality (8.0%,
      95% CI 4.7-11.4), and costs ($28,510 per patient, 95% CI 22,193-34,827).
      CONCLUSIONS: Despite being less common than other injury mechanisms, gunshot
      injuries cause a disproportionate burden of adverse outcomes in children,
      particularly among older adolescent males. Public health, injury prevention, and
      health policy solutions are needed to reduce gunshot injuries in children.

PMID- 24127483
TI  - Genetic lesions associated with chronic lymphocytic leukemia transformation to
      Richter syndrome.
AB  - Richter syndrome (RS) derives from the rare transformation of chronic lymphocytic
      leukemia (CLL) into an aggressive lymphoma, most commonly of the diffuse large B
      cell lymphoma (DLBCL) type. The molecular pathogenesis of RS is only partially
      understood. By combining whole-exome sequencing and copy-number analysis of 9 CLL
      RS pairs and of an extended panel of 43 RS cases, we show that this aggressive
      disease typically arises from the predominant CLL clone by acquiring an average
      of ~20 genetic lesions/case. RS lesions are heterogeneous in terms of load and
      spectrum among patients, and include those involved in CLL progression and
      chemorefractoriness (TP53 disruption and NOTCH1 activation) as well as some not
      previously implicated in CLL or RS pathogenesis. In particular, disruption of the
      CDKN2A/B cell cycle regulator is associated with ~30% of RS cases. Finally, we
      report that the genomic landscape of RS is significantly different from that of
      de novo DLBCL, suggesting that they represent distinct disease entities. These
      results provide insights into RS pathogenesis, and identify dysregulated pathways
      of potential diagnostic and therapeutic relevance. 

PMID- 24127484
TI  - Pathogenic CD4+ T cells recognizing an unstable peptide of insulin are directly
      recruited into islets bypassing local lymph nodes.
AB  - In the nonobese diabetic mouse, a predominant component of the autoreactive
      CD4(+) T cell repertoire is directed against the B:9-23 segment of the insulin B
      chain. Previous studies established that the majority of insulin-reactive T cells
      specifically recognize a weak peptide-MHC binding register within the B:9-23
      segment, that to the 12-20 register. These T cells are uniquely stimulated when
      the B:9-23 peptide, but not the insulin protein, is offered to antigen presenting
      cells (APCs). Here, we report on a T cell receptor (TCR) transgenic mouse (8F10)
      that offers important new insights into the biology of these unconventional T
      cells. Many of the 8F10 CD4(+) T cells escaped negative selection and were highly
      pathogenic. The T cells were directly recruited into islets of Langerhans, where
      they established contact with resident intra-islet APCs. Immunogenic insulin had
      to be presented in order for the T cells to localize and cause disease. These T
      cells bypassed an initial priming stage in the pancreatic lymph node thought to
      precede islet T cell entry. 8F10 T cells induced the production of antiinsulin
      antibodies and islets contained immunoglobulin (IgG) deposited on beta cells and
      along the vessel walls. 

PMID- 24127486
TI  - Transient regulatory T cell ablation deters oncogene-driven breast cancer and
      enhances radiotherapy.
AB  - Rational combinatorial therapeutic strategies have proven beneficial for the
      management of cancer. Recent success of checkpoint blockade in highly immunogenic
      tumors has renewed interest in immunotherapy. Regulatory T (T reg) cells densely
      populate solid tumors, which may promote progression through suppressing anti
      tumor immune responses. We investigated the role of T reg cells in murine mammary
      carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in
      Foxp3(DTR) knockin mice. T reg cell ablation resulted in significant determent of
      primary and metastatic tumor progression. Importantly, short-term ablation of T
      reg cells in advanced spontaneous tumors led to extensive apoptotic tumor cell
      death. This anti-tumor activity was dependent on IFN-gamma and CD4(+) T cells but
      not on NK or CD8(+) T cells. Combination of T reg cell ablation with CTLA-4 or PD
      1/PD-L1 blockade did not affect tumor growth or improve the therapeutic effect
      attained by T reg cell ablation alone. However, T reg cell targeting jointly with
      tumor irradiation significantly reduced tumor burden and improved overall
      survival. Together, our results demonstrate a major tumor-promoting role of T reg
      cells in an autochthonous model of tumorigenesis, and they reveal the potential
      therapeutic value of combining transient T reg cell ablation with radiotherapy
      for the management of poorly immunogenic, aggressive malignancies. 

PMID- 24127487
TI  - Transcription repressor Bach2 is required for pulmonary surfactant homeostasis
      and alveolar macrophage function.
AB  - Pulmonary alveolar proteinosis (PAP) results from a dysfunction of alveolar
      macrophages (AMs), chiefly due to disruptions in the signaling of granulocyte
      macrophage colony-stimulating factor (GM-CSF). We found that mice deficient for
      the B lymphoid transcription repressor BTB and CNC homology 2 (Bach2) developed
      PAP-like accumulation of surfactant proteins in the lungs. Bach2 was expressed in
      AMs, and Bach2-deficient AMs showed alterations in lipid handling in comparison
      with wild-type (WT) cells. Although Bach2-deficient AMs showed a normal
      expression of the genes involved in the GM-CSF signaling, they showed an altered
      expression of the genes involved in chemotaxis, lipid metabolism, and alternative
      M2 macrophage activation with increased expression of Ym1 and arginase-1, and the
      M2 regulator Irf4. Peritoneal Bach2-deficient macrophages showed increased Ym1
      expression when stimulated with interleukin-4. More eosinophils were present in
      the lung and peritoneal cavity of Bach2-deficient mice compared with WT mice. The
      PAP-like lesions in Bach2-deficient mice were relieved by WT bone marrow
      transplantation even after their development, confirming the hematopoietic origin
      of the lesions. These results indicate that Bach2 is required for the functional
      maturation of AMs and pulmonary homeostasis, independently of the GM-CSF
      signaling. 

PMID- 24127488
TI  - Down-regulation of PLCgamma2-beta-catenin pathway promotes activation and
      expansion of myeloid-derived suppressor cells in cancer.
AB  - Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by
      suppressing antitumor T cell responses in many cancers. Although the mechanism of
      T cell inhibition is established, the pathways leading to MDSC accumulation in
      bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear.
      We demonstrate that down-regulation of PLCgamma2 signaling in MDSCs is
      responsible for their aberrant expansion during tumor progression. PLCgamma2(-/-)
      MDSCs show stronger immune-suppressive activity against CD8(+) T cells than WT
      MDSCs and potently promote tumor growth when adoptively transferred into WT mice.
      Mechanistically, PLCgamma2(-/-) MDSCs display reduced beta-catenin levels, and
      restoration of beta-catenin expression decreases their expansion and tumor
      growth. Consistent with a negative role for beta-catenin in MDSCs, its deletion
      in the myeloid population leads to MDSC accumulation and supports tumor
      progression, whereas expression of beta-catenin constitutively active reduces
      MDSC numbers and protects from tumor growth. Further emphasizing the clinical
      relevance of these findings, MDSCs isolated from pancreatic cancer patients show
      reduced p-PLCgamma2 and beta-catenin levels compared with healthy controls,
      similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down
      regulation of PLCgamma2-beta-catenin pathway occurs in mice and humans and leads
      to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic
      beta-catenin blockade as anti-cancer therapy. 

PMID- 24127489
TI  - A common rejection module (CRM) for acute rejection across multiple organs
      identifies novel therapeutics for organ transplantation.
AB  - Using meta-analysis of eight independent transplant datasets (236 graft biopsy
      samples) from four organs, we identified a common rejection module (CRM)
      consisting of 11 genes that were significantly overexpressed in acute rejection
      (AR) across all transplanted organs. The CRM genes could diagnose AR with high
      specificity and sensitivity in three additional independent cohorts (794
      samples). In another two independent cohorts (151 renal transplant biopsies), the
      CRM genes correlated with the extent of graft injury and predicted future injury
      to a graft using protocol biopsies. Inferred drug mechanisms from the literature
      suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for
      nontransplant indications, could regulate specific CRM genes and reduce the
      number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched
      mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of
      the CRM genes, significant reduction of graft-infiltrating cells, and extended
      graft survival. We further validated the beneficial effect of atorvastatin on
      graft survival by retrospective analysis of electronic medical records of a
      single-center cohort of 2,515 renal transplant patients followed for up to 22 yr.
      In conclusion, we identified a CRM in transplantation that provides new
      opportunities for diagnosis, drug repositioning, and rational drug design. 

PMID- 24127492
TI  - Development of a Model Home Health Nurse Internship Program for New Graduates:
      Key Lessons Learned.

PMID- 24127493
TI  - Affecting Change Through Continuing Education: Improving Vaccine Administration
      Technique.

PMID- 24127491
TI  - The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow.
AB  - Neutrophils are recruited from the blood to sites of inflammation, where they
      contribute to immune defense but may also cause tissue damage. During
      inflammation, neutrophils roll along the microvascular endothelium before
      arresting and transmigrating. Arrest requires conformational activation of the
      integrin lymphocyte function-associated antigen 1 (LFA-1), which can be induced
      by selectin engagement. Here, we demonstrate that a subset of P-selectin
      glycoprotein ligand-1 (PSGL-1) molecules is constitutively associated with L
      selectin. Although this association does not require the known lectin-like
      interaction between L-selectin and PSGL-1, the signaling output is dependent on
      this interaction and the cytoplasmic tail of L-selectin. The PSGL-1-L-selectin
      complex signals through Src family kinases, ITAM domain-containing adaptor
      proteins, and other kinases to ultimately result in LFA-1 activation. The PSGL-1
      L-selectin complex-induced signaling effects on neutrophil slow rolling and
      recruitment in vivo demonstrate the functional importance of this pathway. We
      conclude that this is a signaling complex specialized for sensing adhesion under
      flow. 

PMID- 24127495
TI  - The 2013 Karl Meyer Award and Rosalind Kornfeld Award from the Society for
      Glycobiology.

PMID- 24127498
TI  - Certainty in medicine: a moving target.

PMID- 24127490
TI  - Pten loss in the bone marrow leads to G-CSF-mediated HSC mobilization.
AB  - The phosphatase and tumor suppressor PTEN inhibits the phosphoinositol-3-kinase
      (PI3K) signaling pathway and plays a key role in cell growth, proliferation,
      survival, and migration. Pten conditional deletion using MxCre or Scl-CreER(T)
      leads to splenomegaly and leukemia formation, which occurs after the relocation
      of normal hematopoietic stem cells (HSCs) from the bone marrow to the spleen.
      Unexpectedly, dormant HSCs in the bone marrow do not enter the cell cycle upon
      Pten loss, they do not lose self-renewal activity, and they are not exhausted.
      Instead, Pten deficiency causes an up-regulation of the PI3K pathway in myeloid
      cells, but not in HSCs. Strikingly, myeloid cells secrete high levels of G-CSF
      upon Pten loss, leading to the mobilization of HSCs from the bone marrow and
      accumulation in the spleen. After deletion of Pten in mice lacking G-CSF, the
      splenomegaly, myeloproliferative disease, and splenic HSC accumulation are
      rescued. Our data show that although PTEN has little if any role in normal HSCs,
      it is essential to prevent overt G-CSF production by myeloid and stromal cells
      which otherwise causes HSCs to relocate to the spleen followed by lethal leukemia
      initiation. 

PMID- 24127499
TI  - Bone as a regulator of glucose metabolism.
AB  - For a long time the only functions attributed to the skeleton were locomotion and
      calcium storage. Over the last decade, this view has changed. Genetic studies in
      mice have shown that bone metabolism is regulated by the autonomic nervous system
      and interacts with energy metabolism and reproduction. Osteocalcin, one of the
      main organic ingredients of the bone matrix, was discovered to stimulate insulin
      production by the pancreas, as well as energy expenditure and insulin
      sensitivity. Administration of recombinant osteocalcin to mice on a high fat diet
      decreased weight gain and insulin resistance. These unanticipated results
      stimulated studies on osteocalcin and glucose metabolism in humans. This review
      will discuss these clinical studies and their perspective for the future. 

PMID- 24127500
TI  - The increasing incidence of anal cancer: can it be explained by trends in risk
      groups?
AB  - BACKGROUND: Anal cancer incidence is gradually increasing. The cause of this
      increase is not exactly known. This systematic literature review aimed to
      investigate the trend in time of anal cancer incidence and to find an explanation
      for the supposed increase. METHODS: The TRIP database and PubMed were searched
      for trends in time in incidence of anal cancer in the general population, for
      risk factors and risk groups for anal cancer, and for incidence trends in time in
      these risk groups. RESULTS: Age-adjusted incidence rates have increased in all
      Western countries during the last decades, up to 2.2% per year. Infection with
      the oncogenic human papilloma virus is the most important aetiological factor.
      Besides increasing age, other risk factors have been identified: smoking, sexual
      practices, in particular receptive anal intercourse, and being human
      immunodeficiency virus (HIV) positive. The standardised incidence ratio (SIR) is
      significantly increased in HIV-positive men who have sex with men (MSM) (SIR
      77.8), organ transplant recipients (SIR approx. 6) and women with a history of
      cervical cancer (SIR 6) or cervical intraepithelial neoplasia (SIR 16). Absolute
      numbers of HIV-positive MSM and organ transplant recipients have increased
      significantly in the last decades. CONCLUSION: The increasing incidence of anal
      cancer can be partially explained by an increase in the incidence rate in and
      absolute number of the most important risk group: HIV-positive MSM. The
      increasing number of renal transplant recipients probably also contributes.
      Further studies should answer the question whether these risk groups would
      benefit from preventive screening for anal cancer.

PMID- 24127501
TI  - Iron deficiency before and after bariatric surgery: the need for iron
      supplementation.
AB  - Hepcidin inhibits the iron export from duodenal cells and liver cells into the
      plasma and therefore plays a key role in controlling iron homeostasis. In obese
      patients, elevated cytokine production stimulates hepcidin synthesis, causing
      iron to be retained as ferritin in e.g. macrophages (functional iron deficiency).
      In addition, patients often develop iron deficiency after bariatric surgery due
      to malabsorption, which may cause anaemia and thereby lead to complaints such as
      fatigue. In these patients, the absorption of iron may be disrupted because the
      reduction of Fe3+ by gastric acid into Fe2+ (the form that is easily absorbed) is
      not so effective after stomach reduction. Iron absorption is further reduced
      after malabsorptive interventions as a result of bypassing the duodenum and the
      proximal part of the small intestine, where the absorption takes place. Oral iron
      supplements often have little effect after bariatric surgery. Intravenous
      supplements of iron can restore the iron status rapidly after bariatric surgery,
      resulting in fewer symptoms such as fatigue.

PMID- 24127502
TI  - The aetiology of community-acquired pneumonia and implications for patient
      management.
AB  - PURPOSE: Understanding which pathogens are associated with clinical manifestation
      of community-acquired pneumonia (CAP) is important to optimise treatment. We
      performed a study on the aetiology of CAP and assessed possible implications for
      patient management in the Netherlands. METHODS: Patients with CAP attending the
      emergency department of a general hospital were invited to participate in the
      study. We used an extensive combination of microbiological techniques to
      determine recent infection with respiratory pathogens. Furthermore, we collected
      data on clinical parameters and potential risk factors. RESULTS: From November
      2007 through January 2010, 339 patients were included. Single bacterial infection
      was found in 39% of these patients, single viral infection in 12%, and mixed
      bacterial-viral infection in 11%. Streptococcus pneumoniae was the most
      frequently identified pathogen (22%; n=74). Infection with atypical bacteria was
      detected in 69 (20%) of the patients. CONCLUSION: Initial empirical antibiotics
      should be effective against S. pneumoniae, the most common pathogen identified in
      CAP patients. The large proportion of patients with infection with atypical
      bacteria points to the need for improved diagnostic algorithms including atypical
      bacteria, especially since these atypical bacteria are not covered by the first
      choice antibiotic treatment according to the recently revised Dutch guidelines on
      the management of CAP.

PMID- 24127504
TI  - What about this finger?

PMID- 24127503
TI  - Plasmodium falciparum malaria recrudescence occurring 2.5 years after leaving an
      endemic country.
AB  - Malaria tropica is almost exclusively diagnosed within two months after returning
      from an endemic country. We present here a male patient with severe P. falciparum
      malaria diagnosed 2.5 years after returning from Burkina-Faso. We speculate that
      our patient was chronically infected with PF malaria for more than 2 years, with
      an undetectable parasite index and without symptoms. Because of waning immunity
      clinically overt PF malaria was able to develop. This case illustrates the
      importance of malaria suspicion as a cause of illness in immigrants from malaria
      endemic countries. Even when these immigrants did not travel for a long time,
      malaria should be considered in patients with typical symptoms. 

PMID- 24127505
TI  - A 56-year-old man with tongue lesions.

PMID- 24127506
TI  - An uncommon cause of portal vein thrombosis.

PMID- 24127507
TI  - Skin marks in Surinamese people.

PMID- 24127508
TI  - Keeping venomous snakes in the Netherlands: a harmless hobby or a public health
      threat?
AB  - OBJECTIVE: To describe the incidence of venomous snakebites and the hospital
      treatment thereof (if any) amongst private individuals who keep venomous snakes
      as a hobby. STRUCTURE: Descriptive study. METHOD: Private keepers of venomous
      snakes were invited via the social media Facebook, Hyves, Twitter, Google Plus,
      Linked In and two large discussion forums to fill in an online questionnaire on a
      purely voluntary and anonymous basis. RESULTS: In the period from 1 September
      2012 to 31 December 2012, 86 questionnaires were completed by individuals who
      keep venomous snakes as a hobby. One-third of the venomous snake keepers stated
      that they had at some point been bitten by a venomous snake. Out of those, two
      thirds needed hospital treatment and one-third of those bitten required at least
      one, sometimes more, doses of antiserum. The chances of being bitten increased
      the more venomous snakes a person kept. An inventory of the collections of
      venomous snakes being kept further revealed that no antiserum exists for 16 of
      the species, including for the most commonly held venomous snake, the coral
      cobra. CONCLUSION: Keeping venomous snakes as a hobby is not without danger.
      Although in the majority of snakebite cases no antiserum had to be administered,
      there is nevertheless a significant risk of morbidity and sequelae. Preventing
      snakebites in the first place remains the most important safety measure since
      there are no antiserums available for a substantial number of venomous snakes.

PMID- 24127509
TI  - Prolonged hypocalcaemia after pamidronate infusion in Riedel's thyroiditis
      associated hypoparathyroidism.

PMID- 24127510
TI  - The challenge of multidisciplinary research: improving diabetic pregnancy
      together.

PMID- 24127511
TI  - Roseburia hominis: a novel guilty player in ulcerative colitis pathogenesis?

PMID- 24127512
TI  - Molecular and biochemical analysis of the first ARA6 homologue, a RAB5 GTPase,
      from green algae.
AB  - RAB5 GTPases are important regulators of endosomal membrane traffic in yeast,
      plants, and animals. A specific subgroup of this family, the ARA6 group, has been
      described in land plants including bryophytes, lycophytes, and flowering plants.
      Here, we report on the isolation of an ARA6 homologue in a green alga. CaARA6
      (CaRABF1) from Chara australis, a member of the Characeae that is a close
      relative of land plants, encodes a polypeptide of 237 aa with a calculated
      molecular mass of 25.4 kDa, which is highly similar to ARA6 members from
      Arabidopsis thaliana and other land plants and has GTPase activity. When
      expressed in Nicotiana benthamiana leaf epidermal cells, fluorescently tagged
      CaARA6 labelled organelles with diameters between 0.2 and 1.2 um, which co
      localized with fluorescently tagged AtARA6 known to be present on multivesicular
      endosomes. Mutations in the membrane-anchoring and GTP-binding sites altered the
      localization of CaARA6 comparable to that of A. thaliana ARA6 (RABF1). In
      characean internodal cells, confocal immunofluorescence and immunogold electron
      microscopy with antibodies against AtARA6 and CaARA6 revealed ARA6 epitopes not
      only at multivesicular endosomes but also at the plasma membrane, including
      convoluted domains (charasomes), and at the trans-Golgi network. Our findings
      demonstrate that ARA6-like proteins have a more ancient origin than previously
      thought. They indicate further that ARA6-like proteins could have different
      functions in spite of the high similarity between characean algae and flowering
      plants.

PMID- 24127513
TI  - How succulent leaves of Aizoaceae avoid mesophyll conductance limitations of
      photosynthesis and survive drought.
AB  - In several taxa, increasing leaf succulence has been associated with decreasing
      mesophyll conductance (g M) and an increasing dependence on Crassulacean acid
      metabolism (CAM). However, in succulent Aizoaceae, the photosynthetic tissues are
      adjacent to the leaf surfaces with an internal achlorophyllous hydrenchyma. It
      was hypothesized that this arrangement increases g M, obviating a strong
      dependence on CAM, while the hydrenchyma stores water and nutrients, both of
      which would only be sporadically available in highly episodic environments. These
      predictions were tested with species from the Aizoaceae with a 5-fold variation
      in leaf succulence. It was shown that g M values, derived from the response of
      photosynthesis to intercellular CO2 concentration (A:C i), were independent of
      succulence, and that foliar photosynthate delta(13)C values were typical of C3,
      but not CAM photosynthesis. Under water stress, the degree of leaf succulence was
      positively correlated with an increasing ability to buffer photosynthetic
      capacity over several hours and to maintain light reaction integrity over several
      days. This was associated with decreased rates of water loss, rather than
      tolerance of lower leaf water contents. Additionally, the hydrenchyma contained
      ~26% of the leaf nitrogen content, possibly providing a nutrient reservoir. Thus
      the intermittent use of C3 photosynthesis interspersed with periods of no
      positive carbon assimilation is an alternative strategy to CAM for succulent taxa
      (Crassulaceae and Aizoaceae) which occur sympatrically in the Cape Floristic
      Region of South Africa. 

PMID- 24127515
TI  - Does aphid salivation affect phloem sieve element occlusion in vivo?
AB  - To protect against loss of photo-assimilate-rich phloem sap, plants have evolved
      several mechanisms to plug phloem sieve tubes in response to damage. In many
      Fabaceae, each sieve element contains a discrete proteinaceous body called a
      forisome, which, in response to damage, rapidly transforms from a condensed
      configuration that does not impede the flow of sap to a dispersed configuration
      that plugs the sieve element. Aphids and other specialized phloem sap feeders can
      ingest phloem sap from a single sieve element for hours or days, and to do this,
      they must be able to suppress or reverse phloem plugging. A recent study provided
      in vitro evidence that aphid saliva can reverse forisome plugs. The present study
      tested this hypothesis in vivo by inducing forisome plugs which triggered aphids
      to switch behaviour from phloem sap ingestion to salivation into the sieve
      element. After salivating into the sieve element for various periods of time, the
      aphids were instantaneously cryofixed (freeze fixed) in situ on their leaf. The
      state of the forisome was then determined in the penetrated sieve element and in
      nearby non-penetrated sieve elements which served as controls for sieve elements
      not subjected to direct aphid salivation. Forisomes were almost always in close
      contact with the stylet tips and thus came into direct contact with the saliva.
      Nonetheless, forisome plugs in the penetrated sieve element did not revert back
      to a non-plugging state any faster than those in neighbouring sieve elements that
      were not subjected to direct aphid salivation. 

PMID- 24127514
TI  - Biochemical and physiological characterization of fut4 and fut6 mutants defective
      in arabinogalactan-protein fucosylation in Arabidopsis.
AB  - Arabinogalactan-proteins (AGPs) are highly glycosylated hydroxyproline-rich
      glycoproteins present in plant cell walls. AGPs are characterized by arabinose
      /galactose-rich side chains, which define their interactive molecular surface.
      Fucose residues are found in some dicotyledon AGPs, and AGP fucosylation is
      developmentally regulated. We previously identified Arabidopsis thaliana FUT4 and
      FUT6 genes as AGP-specific fucosyltransferases (FUTs) based on their enzymatic
      activities when heterologously expressed in tobacco (Nicotiana tabacum) BY2
      suspension-cultured cells. Here, the functions of FUT4 and FUT6 and the
      physiological roles of fucosylated AGPs were further investigated using
      Arabidopsis fut4, fut6, and fut4/fut6 mutant plants. All mutant plants showed no
      phenotypic differences compared to wild-type plants under physiological
      conditions, but showed reduced root growth in the presence of elevated NaCl.
      However, roots of wild-type and fut4 mutant plants contained terminal fucose
      epitopes, which were absent in fut6 and fut4/fut6 mutant plants as indicated by
      eel lectin staining. Monosaccharide analysis showed fucose was present in wild
      type leaf and root AGPs, but absent in fut4 leaf AGPs and in fut4/fut6 double
      mutant leaf and root AGPs, indicating that FUT4 was required for fucosylation of
      leaf AGPs while both FUT4 and FUT6 contributed to fucosylation of root AGPs.
      Glycome profiling of cell wall fractions from mutant roots and leaves showed
      distinct glycome profiles compared to wild-type plants, indicating that fucosyl
      residues on AGPs may regulate intermolecular interactions between AGPs and other
      wall components. The current work exemplifies the possibilities of refinement of
      cell wall structures by manipulation of a single or a few cell wall biosynthetic
      genes. 

PMID- 24127516
TI  - Complexes of D-type cyclins with CDKs during maize germination.
AB  - The importance of cell proliferation in plant growth and development has been
      well documented. The majority of studies on basic cell cycle mechanisms in plants
      have been at the level of gene expression and much less knowledge has accumulated
      in terms of protein interactions and activation. Two key proteins, cyclins and
      cyclin-dependent kinases (CDKs) are fundamental for cell cycle regulation and
      advancement. Our aim has been to understand the role of D-type cyclins and type A
      and B CDKs in the cell cycle taking place during a developmental process such as
      maize seed germination. Results indicate that three maize D-type cyclins-D2;2,
      D4;2, and D5;3-(G1-S cyclins by definition) bind and activate two different types
      of CDK-A and B1;1-in a differential way during germination. Whereas CDKA-D-type
      cyclin complexes are more active at early germination times than at later times,
      it was surprising to observe that CDKB1;1, a supposedly G2-M kinase, bound in a
      differential way to all D-type cyclins tested during germination. Binding to
      cyclin D2;2 was detectable at all germination times, forming a complex with
      kinase activity, whereas binding to D4;2 and D5;3 was more variable; in
      particular, D5;3 was only detected at late germination times. Results are
      discussed in terms of cell cycle advancement and its importance for seed
      germination. 

PMID- 24127517
TI  - Elicitors from the endophytic fungus Trichoderma atroviride promote Salvia
      miltiorrhiza hairy root growth and tanshinone biosynthesis.
AB  - Biotic elicitors can be used to stimulate the production of secondary metabolites
      in plants. However, limited information is available on the effects of biotic
      elicitors from endophytic fungi on their host plant. Trichoderma atroviride D16
      is an endophytic fungus isolated from the root of Salvia miltiorrhiza and
      previously reported to produce tanshinone I (T-I) and tanshinone IIA (T-IIA).
      Here, the effects of extract of mycelium (EM) and the polysaccharide fraction
      (PSF), produced by T. atroviride D16, on the growth and secondary metabolism of
      S. miltiorrhiza hairy roots are reported. The results indicated that both EM and
      PSF promoted hairy root growth and stimulated the biosynthesis of tanshinones in
      hairy roots. EM slightly suppressed the accumulation of phenolic acids, while PSF
      had no significant influence on the accumulation of these compounds. When
      comparing the effects of EM versus PSF, it was concluded that PSF is one of the
      main active constituents responsible for promoting hairy root growth, as well as
      stimulating biosynthesis of tanshinones in the hairy root cultures. Moreover, the
      transcriptional activity of genes involved in the tanshinone biosynthetic pathway
      increased significantly with PSF treatment. Thus, PSF from endophytic T.
      atroviride D16 affected the chemical composition of the host plant by influencing
      the expression of genes related to the secondary metabolite biosynthetic pathway.
      Furthermore, treatment with PSF can be effectively utilized for large-scale
      production of tanshinones in the S. miltiorrhiza hairy root culture system. 

PMID- 24127518
TI  - Ocean acidification alleviates low-temperature effects on growth and
      photosynthesis of the red alga Neosiphonia harveyi (Rhodophyta).
AB  - This study aimed to examine interactive effects between ocean acidification and
      temperature on the photosynthetic and growth performance of Neosiphonia harveyi.
      N. harveyi was cultivated at 10 and 17.5  degrees C at present (~380 uatm),
      expected future (~800 uatm), and high (~1500 uatm) pCO2. Chlorophyll a
      fluorescence, net photosynthesis, and growth were measured. The state of the
      carbon-concentrating mechanism (CCM) was examined by pH-drift experiments (with
      algae cultivated at 10  degrees C only) using ethoxyzolamide, an inhibitor of
      external and internal carbonic anhydrases (exCA and intCA, respectively).
      Furthermore, the inhibitory effect of acetazolamide (an inhibitor of exCA) and
      Tris (an inhibitor of the acidification of the diffusive boundary layer) on net
      photosynthesis was measured at both temperatures. Temperature affected
      photosynthesis (in terms of photosynthetic efficiency, light saturation point,
      and net photosynthesis) and growth at present pCO2, but these effects decreased
      with increasing pCO2. The relevance of the CCM decreased at 10  degrees C. A pCO2
      effect on the CCM could only be shown if intCA and exCA were inhibited. The
      experiments demonstrate for the first time interactions between ocean
      acidification and temperature on the performance of a non-calcifying macroalga
      and show that the effects of low temperature on photosynthesis can be alleviated
      by increasing pCO2. The findings indicate that the carbon acquisition mediated by
      exCA and acidification of the diffusive boundary layer decrease at low
      temperatures but are not affected by the cultivation level of pCO2, whereas the
      activity of intCA is affected by pCO2. Ecologically, the findings suggest that
      ocean acidification might affect the biogeographical distribution of N. harveyi.

PMID- 24127519
TI  - Nurses' Knowledge and Attitudes Regarding Pain Management in Hospitalized Adults.

PMID- 24127524
TI  - Sensing charges of the Ciona intestinalis voltage-sensing phosphatase.
AB  - Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs)
      is conferred by a voltage-sensing domain (VSD) located in the N terminus. These
      VSDs are constituted by four putative transmembrane segments (S1 to S4)
      resembling those found in voltage-gated ion channels. The putative fourth segment
      (S4) of the VSD contains positive residues that likely function as voltage
      sensing elements. To study in detail how these residues sense the plasma membrane
      potential, we have focused on five arginines in the S4 segment of the Ciona
      intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that
      four arginine-to-histidine mutants, namely R223H to R232H, mediate voltage
      dependent proton translocation across the membrane, indicating that these
      residues transit through the hydrophobic core of Ci-VSP as a function of the
      membrane potential. These observations indicate that the charges carried by these
      residues are sensing charges. Furthermore, our results also show that the
      electrical field in VSPs is focused in a narrow hydrophobic region that separates
      the extracellular and intracellular space and constitutes the energy barrier for
      charge crossing. 

PMID- 24127525
TI  - A point mutation in the human Slo1 channel that impairs its sensitivity to omega
      3 docosahexaenoic acid.
AB  - Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA)
      at nanomolar concentrations reversibly activate human large-conductance Ca(2+)-
      and voltage-gated K(+) (Slo1 BK) channels containing auxiliary beta1 or beta4
      subunits in cell-free patches. Here we examined the action of DHA on the Slo1
      channel without any auxiliary subunit and sought to elucidate the biophysical
      mechanism and the molecular determinants of the DHA sensitivity. Measurements of
      ionic currents through human Slo1 (hSlo1) channels reveal that the stimulatory
      effect of DHA does not require activation of the voltage or Ca(2+) sensors.
      Unlike gating of the hSlo1 channel, that of the Drosophila melanogaster Slo1
      (dSlo1) channel is unaltered by DHA. Our mutagenesis study based on the
      differential responses of human and dSlo1 channels to DHA pinpoints that Y318
      near the cytoplasmic end of S6 in the hSlo1 channel is a critical determinant of
      the stimulatory action of DHA. The mutation Y318S in hSlo1, which replaces Y with
      S as found in dSlo1, greatly diminishes the channel's response to DHA with a 22
      carbon chain whether beta1 or beta4 is absent or present. However, the responses
      to alpha-linolenic acid, an omegea-3 fatty acid with an 18-carbon chain, and to
      arachidonic acid, an omega-6 fatty acid with a 20-carbon chain, remain unaffected
      by the mutation. Y318 in the S6 segment of hSlo1 is thus an important determinant
      of the electrophysiological response of the channel to DHA. Furthermore, the
      mutation Y318S may prove to be useful in dissecting out the complex lipid
      mediated modulation of Slo1 BK channels. 

PMID- 24127526
TI  - The role of transmembrane channel-like proteins in the operation of hair cell
      mechanotransducer channels.
AB  - Sound stimuli elicit movement of the stereocilia that make up the hair bundle of
      cochlear hair cells, putting tension on the tip links connecting the stereocilia
      and thereby opening mechanotransducer (MT) channels. Tmc1 and Tmc2, two members
      of the transmembrane channel-like family, are necessary for mechanotransduction.
      To assess their precise role, we recorded MT currents elicited by hair bundle
      deflections in mice with null mutations of Tmc1, Tmc2, or both. During the first
      postnatal week, we observed a normal MT current in hair cells lacking Tmc1 or
      Tmc2; however, in the absence of both isoforms, we recorded a large MT current
      that was phase-shifted 180 degrees , being evoked by displacements of the hair
      bundle away from its tallest edge rather than toward it as in wild-type hair
      cells. The anomalous MT current in hair cells lacking Tmc1 and Tmc2 was blocked
      by FM1-43, dihydrostreptomycin, and extracellular Ca(2+) at concentrations
      similar to those that blocked wild type. MT channels in the double knockouts
      carried Ca(2+) with a lower permeability than wild-type or single mutants. The MT
      current in double knockouts persisted during exposure to submicromolar Ca(2+),
      even though this treatment destroyed the tip links. We conclude that the Tmc
      isoforms do not themselves constitute the MT channel but are essential for
      targeting and interaction with the tip link. Changes in the MT conductance and
      Ca(2+) permeability observed in the absence of Tmc1 mutants may stem from loss of
      interaction with protein partners in the transduction complex. 

PMID- 24127530
TI  - Rocking the Boat: Challenges Ahead for Continuing Education Providers.

PMID- 24127527
TI  - Keeping you healthy: BK channel activation by omega-3 fatty acids.

PMID- 24127528
TI  - Who needs tip links? Backwards transduction by hair cells.

PMID- 24127531
TI  - Health-related quality of life in Turner syndrome and the influence of key
      features.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQoL) in a group of girls
      with Turner syndrome (TS) and determine its relation to key features of the
      condition. METHODS: HRQoL was assessed with the short-form health survey (SF-36).
      RESULTS: Of the 35 girls, 32 [mean (SD) age: 16.7 (2.61) years], of whom 28
      (87.6%) received growth hormone therapy, agreed to participitate. Compared with
      the general population, girls with TS have lower scores in the physical
      functioning domain of HRQoL. However, they have similar HRQoL as their peers in
      other dimensions. There was a negative and significant association between the
      postmenarchal status and the social functioning domain of HRQoL. Age at growth
      hormone treatment initiation has a negative impact on the general health domain.
      Age at growth hormone initiation, bone mineral apparent density (BMAD) and the
      prevalence of skeletal anomalies negatively influence the vitality domain. HRQoL
      scores in the physical function domain were negatively associated with BMAD and
      positively associated with height. CONCLUSION: Compared with the general
      population, Irish girls with TS have similar HRQoL in most of domains as their
      peers. Postmenarchal status, height, age at growth hormone initiation, BMAD and
      skeletal anomalies showed significant association with at least one domain of
      HRQOL.

PMID- 24127532
TI  - Leprechaunism (Donohue syndrome): report of a case in a newborn.

PMID- 24127533
TI  - The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and
      PITX2 in familial and sporadic thyroid hemiagenesis.
AB  - BACKGROUND: The molecular mechanisms leading to the formation of the two thyroid
      symmetrical lobes, which are impaired in thyroid hemiagenesis (TH), are little
      known. OBJECTIVE: The aim of this work was to search for mutations in thyroid
      developmental candidate genes HOXA3, HOXB3, HOXD3 and PITX2. METHODS: Total DNA
      from peripheral blood was extracted and then the entire coding region of all
      these genes was amplified by polymerase chain reaction and direct sequencing.
      RESULTS: Herein we describe familial cases of TH in two generations (proband and
      his father), in addition to other two sporadic cases. We have found polymorphisms
      in the HOXB3 (rs2229304), HOXD3 (rs34729309, rs1051929, c.543-199G>T and c.543
      34G>A; and a new synonymous variant, NP_008829.3:p.314;C>G) and PITX2
      (c.45+76C>T) genes, but no deleterious mutations. CONCLUSION: These results
      suggest the existence of other left-right thyroid asymmetry candidate genes in
      humans such as classical Mendelian mutation-causing disease, as well as other
      etiopathogenic mechanisms such as epigenetic modifications, especially for
      sporadic hemiagenesis.

PMID- 24127534
TI  - Children and adolescents with type 1 diabetes mellitus have a sixfold greater
      risk for prolonged QTc interval.
AB  - BACKGROUND: QT-wave abnormalities have been detected in type 1 diabetes mellitus
      (T1DM). Prolongation of the heart rate corrected QT interval (QTc) has been
      associated with cardiovascular mortality. We evaluated how often QT/QTc
      abnormalities are present in youth with T1DM and if they are associated with
      disease parameters. METHODS: Sixty-two T1DM youngsters and equal age- and gender
      matched controls were studied. Demographic, anthropometric, and laboratory data
      were determined. QT was measured on a 12-lead resting electrocardiogram. QTc was
      calculated using Bazett's formula. RESULTS: T1DM patients had significantly
      longer QT/QTc than controls, but significance disappeared after adjustment for
      confounders. Abnormally prolonged QTc>=440 ms was observed six times more
      frequently in those with T1DM. QT was correlated with age, age at disease onset,
      but not with glycated hemoglobin or diabetes duration; QTc was only correlated
      with pubertal stage. CONCLUSIONS: T1DM youths have a sixfold increased risk for
      QT/QTc prolongation and should have regular follow-up for cardiac autonomic
      dysfunction.

PMID- 24127535
TI  - Radiologic manifestation of a BCS1L-mutated patient.
AB  - There are various phenotypes of mutations in BCS1L which encode a mitochondrial
      inner membrane protein that facilitates the insertion of Rieske iron-sulfur
      protein into respiratory chain complex III. Herein we report the radiologic
      findings of a patient with bc1 synthesis-like (BCS1L) gene mutation who was
      presented with convulsions.

PMID- 24127536
TI  - A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism.
AB  - Mutations in DUOX2 have been reported to cause congenital hypothyroidism (CH),
      and our aim in this study was to determine the genetic basis of CH in two
      affected individuals coming from a consanguineous family. Because CH is usually
      inherited in autosomal recessive manner in consanguineous/multicase families, we
      adopted a two-stage strategy of genetic linkage studies and targeted sequencing
      of the candidate genes. First, we investigated the potential genetic linkage of
      the family to any known CH locus using microsatellite markers and then screened
      for mutations in linked genes by Sanger sequencing. The family showed potential
      linkage to DUOX2 locus and we detected a nonsense mutation (R434X) in both cases
      and the mutation segregated with disease status in the family. This study
      highlights the importance of molecular genetic studies in the definitive
      diagnosis and classification of CH, and it also suggests a new clinical testing
      strategy using next-generation sequencing in all primary CH cases.

PMID- 24127537
TI  - Visual callosal connections: role in visual processing in health and disease.
AB  - Visual cortical areas in the two sides of the brain are interconnected by
      interhemispheric fibers passing through the splenium of the corpus callosum. In
      this review, we summarize data concerning the anatomical features of visual
      callosal connections, their roles in basic visual processing, and how their
      alterations contribute to visual deficits in different human neuropathologies.
      Splenial fibers represent a population of excitatory axons with varying
      diameters, which interconnect cortical columns with similar functional properties
      (i.e., same orientation selectivity) in the two hemispheres. Their branches
      activate simultaneously distinct iso-oriented columns in the contralateral
      hemisphere, thus mediating forms of stimulus-dependent interhemispheric
      synchronization. Callosal branches also make synapses onto GABAergic cells,
      resulting in an inhibitory modulation of visual processing that involves both iso
      oriented and cross-oriented cortical networks. Interhemispheric inhibition
      appears to predominate at short latencies following callosal activation, whereas
      excitation becomes more robust with increasing delays. These callosal effects are
      dynamically adapted to the incoming visual activity, so that stimuli providing
      only weak afferent input are facilitated by callosal pathways, whereas strong
      visual input via the retinogeniculate pathway tends to be offset by transcallosal
      inhibition. We also review data highlighting the contribution of callosal input
      activity to maturation of visual function during early 'critical periods' in
      brain development and describe how interhemispheric transfer of visual
      information is rerouted in cases of callosal agenesis or following splenial
      damage. Finally, we provide an overview of alterations in splenium anatomy or
      function that may be at the basis of visual defects in several pathologic
      conditions.

PMID- 24127539
TI  - Calcium-dependent mechanisms mediate the vasorelaxant effects of Tridax
      procumbens (Lin) aqueous leaf extract in rat aortic ring.
AB  - BACKGROUND: Tridax procumbens leaf extract has a folk reputation as an
      antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant
      effect on smooth muscles. The present study was designed to investigate the role
      of calcium in the vasorelaxant effect of this extract. METHODS: Concentration
      response studies with noradrenaline (NA), KCl and CaCl2 were carried out in rat
      aortic rings with and without the extract in physiological salt solution (PSS)
      (n=6 each). Also, the role of intracellular calcium mobilization was studied by
      measuring the phasic response to NA in Ca2+-free N,N-ethylene glycol tetraacetic
      acid (EGTA) PSS (n=6). RESULTS: The results showed that the contractile responses
      to either NA or KCl were attenuated (p<0.05) in the presence of the extract.
      Also, the extract attenuated the contractile response to CaCl2 in the presence of
      NA or KCl (p<0.05) in the Ca2+-free EGTA PSS, while the phasic response to NA was
      significantly (p<0.05) diminished. CONCLUSIONS: These results suggest that the
      vasorelaxant effect of T. procumbens leaf extract may be mediated by a non
      specific, non-competitive inhibition of Ca2+ influx as well as by inhibition of
      Ca2+ mobilization from intracellular stores. This implies that it may contain
      vasorelaxant agents that may have calcium antagonistic potential.

PMID- 24127538
TI  - Evaluation of in vitro aldose reductase inhibitory potential of alkaloidal
      fractions of Piper nigrum, Murraya koenigii, Argemone mexicana, and Nelumbo
      nucifera.
AB  - BACKGROUND: Aldose reductase is primarily involved in development of long-term
      diabetic complications due to increased polyol pathway activity. The synthetic
      aldose reductase inhibitors are not very successful clinically. Therefore, the
      natural sources may be exploited for safer and effective aldose reductase
      inhibitors. METHODS: In the present study, the aldose reductase inhibitory
      potential of hydroalcoholic and alkaloidal extracts of Piper nigrum, Murraya
      koenigii, Argemone mexicana, and Nelumbo nucifera was evaluated. The
      hydroalcoholic and alkaloidal extracts of the selected plants were prepared. The
      different concentrations of hydroalcoholic and alkaloidal extracts of these
      plants were evaluated for their goat lens aldose reductase inhibitory activity
      using dl-glyceraldehyde as substrate. The aldose reductase inhibitory potential
      of extracts was assessed in terms of their IC50 value. RESULTS: Amongst the
      hydroalcoholic extracts, the highest aldose reductase inhibitory activity was
      shown by P. nigrum (IC50 value 35.64+/-2.7 MUg/mL) followed by M. koenigii (IC50
      value 45.67+/-2.57 MUg/mL), A. mexicana (IC50 value 56.66+/-1.30 MUg/mL), and N.
      nucifera (IC50 value 59.78+/-1.32 MUg/mL). Among the alkaloidal extracts, highest
      inhibitory activity was shown by A. mexicana (IC50 value 25.67+/-1.25 MUg/mL),
      followed by N. nucifera (IC50 value 28.82+/-1.85 MUg/mL), P. nigrum (IC50 value
      30.21+/-1.63 MUg/mL), and M. koenigii (IC50 value 35.66+/-1.64 MUg/mL).
      CONCLUSIONS: It may be concluded that the alkaloidal extracts of these plants
      possess potent aldose reductase inhibitory activity and may be therapeutically
      exploited in diabetes-related complications associated with increased activity of
      aldose reductase.

PMID- 24127540
TI  - Methylglyoxal causes endothelial dysfunction: the role of endothelial nitric
      oxide synthase and AMP-activated protein kinase alpha.
AB  - BACKGROUND: Methylglyoxal is a major precursor in the formation of advanced
      glycation end products and is associated with the pathogenesis of diabetes
      related vascular complications. The aim of this study was to evaluate whether
      methylglyoxal induces endothelial dysfunction and to determine the contributors
      involved in this process. METHODS: Rat thoracic aortic rings were treated for 24
      h with 100 MUM methylglyoxal by using an organ culture method. A cumulative dose
      response curve to acetylcholine was obtained to determine endothelium-dependent
      relaxation. The protein levels of endothelial nitric oxide synthase (eNOS) and
      its phosphorylated form at the serine 1177 site [p-eNOS (Ser1177)], heat shock
      protein 90 (Hsp90), AMP-activated protein kinase alpha (AMPKalpha) and its
      phosphorylated form at the threonine 172 site [p-AMPKalpha (Thr172)] were
      evaluated. Superoxide production was determined by lucigenin-chemiluminescence.
      RESULTS: Treatment with 100 MUM methylglyoxal for 24 h decreased acetylcholine
      induced vascular relaxation. The levels of eNOS and p-eNOS (Ser1177) were reduced
      while no effect on Hsp90 was observed. Levels of p-AMPKalpha (Thr172) were
      significantly decreased without any change in total AMPKalpha protein levels.
      Superoxide level was not affected by methylglyoxal treatment. CONCLUSIONS: In rat
      aortic rings, methylglyoxal determines a reduction in endothelium-dependent
      relaxation. This effect seems to be mediated via a reduction in p-eNOS (Ser1177)
      and p-AMPKalpha (Thr172).

PMID- 24127541
TI  - The role of oxidative stress during inflammatory processes.
AB  - Abstract The production of various reactive oxidant species in excess of
      endogenous antioxidant defense mechanisms promotes the development of a state of
      oxidative stress, with significant biological consequences. In recent years,
      evidence has emerged that oxidative stress plays a crucial role in the
      development and perpetuation of inflammation, and thus contributes to the
      pathophysiology of a number of debilitating illnesses, such as cardiovascular
      diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all
      stages of the inflammatory response, including the release by damaged tissues of
      molecules acting as endogenous danger signals, their sensing by innate immune
      receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the
      activation of signaling pathways initiating the adaptive cellular response to
      such signals. In this article, after summarizing the basic aspects of redox
      biology and inflammation, we review in detail the current knowledge on the
      fundamental connections between oxidative stress and inflammatory processes, with
      a special emphasis on the danger molecule high-mobility group box-1, the TLRs,
      the NLRP-3 receptor, and the inflammasome, as well as the transcription factor
      nuclear factor-kappaB. 

PMID- 24127542
TI  - Septin 9 amplification and isoform-specific expression in peritumoral and tumor
      breast tissue.
AB  - Septins are a large family of GTP-binding proteins abnormally expressed in many
      solid tumors. Septin 9 (SEPT9) in particular has been found overexpressed in
      diverse human tumors including breast, head and neck, ovarian, endometrial,
      kidney, and pancreatic cancer. Although we previously reported SEPT9
      amplification in breast cancer, we now show specifically that high-grade breast
      carcinomas, the subtype with worst clinical outcome, exhibit a significant
      increase in SEPT9 copy number when compared with other tumor grades. We also
      present, for the first time, a sensitive and quantitative measure of seven
      (SEPT9_v1 through SEPT9_v7) isoform variant mRNA levels in mammary epithelial
      cells. SEPT9_v1, SEPT9_v3, SEPT9_v6, and SEPT9_v7 isoforms were expressed at the
      highest levels followed by SEPT9_v2 and SEPT9_v5, whereas SEPT9_v4 was almost
      undetectable. Although most of the isoforms were upregulated in primary tumor
      tissues relative to the patient-matched peritumoral tissues, SEPT9_v4 remained
      the lowest expressing isoform. This comprehensive analysis of SEPT9 provides
      substantial evidence for increased SEPT9 expression as a consequence of genomic
      amplification and is the first study to profile SEPT9_v1 through SEPT9_v7 isoform
      specific mRNA expression in tumor and nontumor tissues from patients with breast
      cancer.

PMID- 24127543
TI  - Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and
      reproducibility.
AB  - BACKGROUND: We have developed a PCR-based tool that measures a 51-gene panel for
      identification of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) in
      peripheral blood. This manuscript assesses the robustness (performance metrics)
      of this tool with a specific focus on the effects of individual parameters
      including collection, storage, acid suppressive medication [proton pump inhibitor
      (PPI)], age, sex, race and food on accuracy. METHODS: Performance metrics were
      evaluated using a gold standard (mRNA derived from three individual human
      neuroendocrine tumor cell lines) and clinical samples using qPCR. RESULTS: One
      hundred percent of the 51 transcripts were amplified in the gold standard (NEN
      cell line-derived mRNA) (CQ<35, average efficiency 1.94). The inter- and intra
      assay variations were 1%-2%. In clinical samples, 50 of 51 targets (98%) were
      amplified. The inter- and intra-assay reproducibility ranged between 0.4% and
      1.2%. The coefficient of variation (CV) was 5.3%. Expression of the reference
      gene, ALG9, was robust [low variation, low M-value, high (99.5%) PCR efficiency]
      and unaffected by sample processing. Test meals, long-term PPI use (>1 year),
      age, sex and ethnicity had no effect on the signature. Expression of two genes,
      ALP2 and CD59 correlated strongly with RNA integrity (R=0.72, p<0.001) and could
      be used to assess storage and processing. CONCLUSIONS: The 51 marker gene
      signature was robust and reproducible, exhibiting acceptable inter- and intra
      assay metrics (<5%). Feeding, PPI intake, age, sex and ethnicity do not affect
      the signature. Expression levels of APLP2 and CD59 are effective surrogate
      markers of proper sample collection and processing.

PMID- 24127544
TI  - Effects of dinuclear berenil-platinum(II) complexes on fibroblasts redox status.
AB  - PURPOSE: Platinum(II) complex anticarcinogenic mechanisms are associated with
      changes in the cellular redox status of cancer as well as healthy cells.
      Therefore, the goal of the present study was to investigate oxidative
      modifications in cellular components following fibroblast exposure to novel
      dinuclear berenil-platinum(II) complexes. MATERIAL AND METHOD: ROS levels,
      antioxidant parameters level/activity, and damage to DNA, lipids, and proteins,
      including pro-apoptotic and anti-apoptotic factors in human skin fibroblasts
      following berenil-platinum(II) complex treatments i.e.
      Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)4, Pt2(2
      picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4- picoline)4(berenil)2
      were examined. RESULTS: Treatment of fibroblasts with platinum(II) complexes has
      shown that all compounds enhance total ROS and superoxide anion generation as
      well as change the activity of antioxidant enzymes such as superoxide dismutase,
      catalase, glutathione peroxidase and glutathione reductase and decrease in the
      level of non-enzymatic antioxidants (GSH, vitamin C, E and A). Such a situation
      is conducive to oxidative stress formation and oxidative modifications of
      cellular macromolecules and to increase in the expression of proapoptotic
      proteins. Pt2(isopropylamine)4(berenil)2 elicited the most damage, which resulted
      in oxidative modification of cellular components. The therapeutic use of this
      complex would cause considerable side effects in patients, therefore the agent
      lacks drug potential; however Pt2(piperazine)4(berenil)2 and Pt2(2
      picoline)4(berenil)2 exhibited reduced redox and increased apoptotic profiles
      compared to cisplatin. CONCLUSION: Results of this paper and preliminary data
      show that Pt2(2-picoline)4(berenil)2 is less dangers than cisplatin to
      fibroblasts and more disruptive than cisplatin to breast cancer cell metabolism,
      and therefore it is a promising candidate for use in future anticancer drug
      strategies.

PMID- 24127545
TI  - Exact nonparametric confidence bands for the survivor function.
AB  - A method to produce exact simultaneous confidence bands for the empirical
      cumulative distribution function that was first described by Owen, and
      subsequently corrected by Jager and Wellner, is the starting point for deriving
      exact nonparametric confidence bands for the survivor function of any positive
      random variable. We invert a nonparametric likelihood test of uniformity,
      constructed from the Kaplan-Meier estimator of the survivor function, to obtain
      simultaneous lower and upper bands for the function of interest with specified
      global confidence level. The method involves calculating a null distribution and
      associated critical value for each observed sample configuration. However, Noe
      recursions and the Van Wijngaarden-Decker-Brent root-finding algorithm provide
      the necessary tools for efficient computation of these exact bounds. Various
      aspects of the effect of right censoring on these exact bands are investigated,
      using as illustrations two observational studies of survival experience among non
      Hodgkin's lymphoma patients and a much larger group of subjects with advanced
      lung cancer enrolled in trials within the North Central Cancer Treatment Group.
      Monte Carlo simulations confirm the merits of the proposed method of deriving
      simultaneous interval estimates of the survivor function across the entire range
      of the observed sample. This research was supported by the Natural Sciences and
      Engineering Research Council (NSERC) of Canada. It was begun while the author was
      visiting the Department of Statistics, University of Auckland, and completed
      during a subsequent sojourn at the Medical Research Council Biostatistics Unit in
      Cambridge. The support of both institutions, in addition to that of NSERC and the
      University of Waterloo, is greatly appreciated.

PMID- 24127546
TI  - On the effects of malaria treatment on parasite drug resistance--probability
      modelling of genotyped malaria infections.
AB  - We compare the frequency of resistant genes of malaria parasites before treatment
      and at first malaria incidence after treatment. The data come from a clinical
      trial at two health facilities in Tanzania and concerns single nucleotide
      polymorphisms (SNPs) at three positions believed to be related to resistance to
      malaria treatment. A problem is that mixed infections are common, which both
      obscures the underlying frequency of alleles at each locus as well as the
      associations between loci in samples where alleles are mixed. We use
      combinatorics and quite involved probability methods to handle multiple
      infections and multiple haplotypes. The infection with the different haplotypes
      seemed to be independent of each other. We showed that at two of the three
      studied SNPs, the proportion of resistant genes had increased after treatment
      with sulfadoxine-pyrimethamine alone but when treated in combination with
      artesunate, no effect was noticed. First recurrences of malaria associated more
      with sulfadoxine-pyrimethamine alone as treatment than when in combination with
      artesunate. We also found that the recruited children had two different ongoing
      malaria infections where the parasites had different gene types.

PMID- 24127547
TI  - Chemical and pharmacological standardization of Ashwagandhadi lehyam: an
      ayurvedic formulation.
AB  - Standardization is an important measurement for ensuring the quality control of
      herbal drugs. It has become essential to develop reliable, specific and sensitive
      quality control methods. One of the prime ingredients of Ashwagandhadi lehyam is
      Withania somnifera L. Dunal (Solanaceae) (ashwagandha). In the present study,
      Ashwagandhadi lehyam was formulated and the quality assessment of the formulation
      was based on phytochemical screening and physico-chemical evaluation.
      Ashwagandhadi lehyam was formulated according to a working formula and subjected
      to phytochemical screening by FTIR analysis and HPTLC fingerprinting, heavy metal
      determination by AAS, determination of alcohol content, tested for Escherichia
      coli, Staphylococcus aureus, aerobic bacteria, yeasts and mould, oral toxicity
      studies and anti-epileptic activity by MES method. The physico-chemical studies
      showed total ash content as 6.45%, extractive values and some trace elements such
      as lead, mercury, cadmium and arsenic with 3.2, 0.05, 0.18 and 0.48 ppm,
      respectively. FTIR and HPTLC studies revealed the presence of functional groups
      of withanolides in Ashwagandhadi lehyam, resulting in its chemical
      standardization. The formulation exhibited less epileptic seizures in various
      phases when compared with that of standard phenytoin and found to possess better
      anti-inflammatory activity, thus making it biologically standardized. The physico
      chemical and pharmacological analysis to standardize Ashwagandhadi lehyam
      confirmed its use as a safe anti-inflammatory agent and for various seizure
      disorders.

PMID- 24127548
TI  - Phylogeography of the dark fruit-eating bat Artibeus obscurus in the Brazilian
      Amazon.
AB  - Artibeus obscurus (Mammalia: Chiroptera) is endemic to South America, being found
      in at least 18 Brazilian states. Recent studies revealed that different
      populations of this genus present distinct phylogeographic patterns; however,
      very little is known on the population genetics structure of A. obscurus in the
      Amazon rainforest. Here, using a fragment (1010bp) of the mitochondrial gene
      cytochrome b from 87 samples, we investigated patterns of genetic divergence
      among populations of A. obscurus from different locations in the Brazilian Amazon
      rainforest and compared them with other Brazilian and South American regions.
      Analysis of molecular variance (AMOVA), fixation index (Fst) analysis, and
      phylogeographic patterns showed divergence between two major monophyletic groups,
      each one corresponding to a geographic region associated with the Atlantic and
      Amazon forest biomes. The Atlantic forest clusters formed a monophyletic group
      with a high bootstrap support and a fragmented distribution that follows the
      pattern predicted by the Refuge Theory. On the other hand, a different scenario
      was observed for the Amazon forest, where no fragmentation was identified. The
      AMOVA results revealed a significant geographic heterogeneity in the distribution
      of genetic variation, with 70% found within populations across the studied
      populations (Fst values ranging from 0.05864 to 0.09673; phiST = 0.55). The
      intrapopulational analysis revealed that one population (Braganca) showed
      significant evidence of population expansion, with the formation of 2 distinct
      phylogroups, suggesting the occurrence of a subspecies or at least a different
      population in this region. These results also suggest considerable heterogeneity
      for A. obscurus in the Amazon region.

PMID- 24127549
TI  - Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate
      cancer.
AB  - Histone variants seem to play a major role in gene expression regulation. In
      prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes'
      upregulation. SIRT1, which may act either as tumor suppressor or oncogene,
      reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and
      this mechanism might be impaired in prostate cancer cells due to sirtuin 1
      downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z
      and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found
      that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript
      level in primary prostate cancer and high-grade prostatic intraepithelial
      neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in
      prostate cancer cell lines resulted in almost complete absence of H2A.Z.
      Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition
      prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate
      cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or
      combined with 5-aza-2'-deoxycytidine, increased H2AFZ transcript, although with a
      concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein
      levels increased after exposure. ChIP revealed an increase of activation marks
      within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with
      nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by
      resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay
      showed that exposure to epigenetic modifying drugs fostered the interaction
      between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation
      in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly
      histone post-translational modifications, are likely involved and impair sirtuin
      1-mediated downregulation of H2A.Z via proteasome-mediated degradation.
      Epigenetic modifying drugs in conjunction with enzymatic modulators are able to
      restore the normal functions of sirtuin 1 and might constitute relevant tools for
      targeted therapy of prostate cancer patients. 

PMID- 24127550
TI  - DHH-RHEBL1 fusion transcript: a novel recurrent feature in the new landscape of
      pediatric CBFA2T3-GLIS2-positive acute myeloid leukemia.
AB  - Childhood Acute Myeloid Leukemia (AML) is a clinically and genetically
      heterogeneous malignant disease. Despite improvements in outcome over the past
      decades, the current survival rate still is approximately 60-70%. Cytogenetic,
      recurrent genetic abnormalities and early response to induction treatment are the
      main factors predicting clinical outcome. While the majority of children carry
      recurrent chromosomal translocations, 20% of patients do not show any
      recognizable cytogenetic alteration and are defined to have cytogenetically
      normal AML (CN-AML). This subset of patients is characterized by a significant
      heterogeneity in clinical outcome, which is influenced by factors only recently
      started to be identified. In this respect, genome-wide analyses have been used
      with the aim of defining the full array of genetic lesions in CN-AML. Recently,
      through whole-transcriptome massively parallel sequencing of seven cases of
      pediatric CN-AML, we identified a novel recurrent CBFA2T3-GLIS2 fusion,
      predicting poorer outcome. However, since the expression of CBFA2T3-GLIS2 fusion
      in mice is not sufficient for leukemogenesis, we speculated that further unknown
      abnormalities could contribute to both cancer transformation and response to
      treatment. Thus, we analyzed, by whole-transcriptome sequencing, 4 CBFA2T3-GLIS2
      positive patients, as well as 4 CN-AML patients. We identified a new fusion
      transcript in the CBFA2T3-GLIS2-positive patients, involving Desert Hedgehog
      (DHH), a member of Hedgehog family, and Ras Homologue Enrich in Brain Like 1
      (RHEBL1), a gene coding for a small GTPase of the Ras family. Through the
      screening of a validation cohort of 55 additional pediatric AML patients, we
      globally detected DHH-RHEBL1 fusion in 8 out of 20 (40%) CBFA2T3-GLIS2-rearranged
      patients. Gene expression analysis performed on RNA-seq data revealed that DHH
      RHEBL1-positive patients exhibited a specific signature. These 8 patients had an
      8-year overall survival worse than that of the remaining 12 CBFA2T3-GLIS2
      rearranged patients not harboring DHH-RHEBL1 fusion (25% vs 55%, respectively,
      P=0.1). Taken together, these findings are unprecedented and indicate that the
      DHH-RHEBL1 fusion transcript is a novel recurrent feature in the changing
      landscape of CBFA2T3-GLIS2-positive childhood AML. Moreover, it could be
      instrumental in the identification of a subgroup of CBFA2T3-GLIS2-positive
      patients with a very poor outcome. 

PMID- 24127552
TI  - Education in High-Performing Hospitals: Using the Baldrige Framework to
      Demonstrate Positive Outcomes.

PMID- 24127551
TI  - Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal
      survival.
AB  - Glioblastoma (GBM) is the most malignant brain tumor where patients' survival is
      only 14.6 months, despite multimodal therapy with debulking surgery, concurrent
      chemotherapy and radiotherapy. There is an urgent, unmet need for novel,
      effective therapeutic strategies for this devastating disease. Although several
      immunotherapies are under development for the treatment of GBM patients, the use
      of natural killer (NK) cells is still marginal despite this being a promising
      approach to treat cancer. In regard of our knowledge on the role of NG2/CSPG4 in
      promoting GBM aggressiveness we investigated the potential of an innovative
      immunotherapeutic strategy combining mAb9.2.27 against NG2/CSPG4 and NK cells in
      preclinical animal models of GBM. Multiple immune escape mechanisms maintain the
      tumor microenvironment in an anti-inflammatory state to promote tumor growth,
      however, the distinct roles of resident microglia versus recruited macrophages is
      not elucidated. We hypothesized that exploiting the cytokine release capabilities
      of activated (NK) cells to reverse the anti-inflammatory axis combined with
      mAb9.2.27 targeting the NG2/CSPG4 may favor tumor destruction by editing pro-GBM
      immune responses. Combination treatment with NK+mAb9.2.27 diminished tumor growth
      that was associated with reduced tumor proliferation, increased cellular
      apoptosis and prolonged survival compared to vehicle and monotherapy controls.
      The therapeutic efficacy was mediated by recruitment of CCR2low macrophages into
      the tumor microenvironment, increased ED1 and MHC class II expression on
      microglia that might render them competent for GBM antigen presentation, as well
      as elevated IFN-gamma and TNF-alpha levels in the cerebrospinal fluid compared to
      controls. Depletion of systemic macrophages by liposome-encapsulated clodronate
      decreased the CCR2low macrophages recruited to the brain and abolished the
      beneficial outcomes. Moreover, mAb9.2.27 reversed tumor-promoting effects of
      patient-derived tumor-associated macrophage/microglia(TAM) ex vivo.Taken
      together, these findings indicate thatNK+mAb9.2.27 treatment may be an amenable
      therapeutic strategy to treat NG2/CSPG4 expressing GBMs. We provide a novel
      conceptual approach of combination immunotherapy for glioblastoma. The results
      traverse beyond the elucidation of NG2/CSPG4 as a therapeutic target, but
      demonstrate a proof of concept that this antibody may hold potential for the
      treatment of GBM by activation of tumor infiltrated microglia/macrophages. 

PMID- 24127553
TI  - Lyn mitigates mouse airway remodeling by downregulating the TGF-beta3 isoform in
      house dust mite models.
AB  - Chronic airway remodeling is a serious consequence of asthma, which is caused by
      complex but largely unknown mechanisms. Despite versatile functions, the role of
      Lyn in chronic airway remodeling remains undefined. Using Lyn(-/-) mice, we show
      that continual exposure (for 8 wk) of house dust mite extracts induced a severe
      phenotype of chronic airway remodeling, including exacerbated mucus production,
      collagen deposition, dysregulated cytokine secretion, and elevated inflammation.
      Strikingly, a significant increase in TGF-beta3 rather than TGF-beta1 was
      observed in Lyn(-/-) mouse lungs compared with lungs in wild-type mice.
      Furthermore, TGF-beta3 neutralizing Abs not only inhibited the expression of
      STAT6 and Smad2/3 but also decreased phosphorylation of Smad2 and NF-kappaB in
      Lyn(-/-) mouse lungs. In addition, both recombinant and adenoviral TGF-beta3
      significantly promoted epithelial-to-mesenchymal transition and intensified
      collagen I production and MUC5AC expression. Further examination of chronic
      asthma patients showed that a decreased Lyn correlated with the severity of
      airway inflammation and mucus hypersecretion. Finally, Lyn may critically
      regulate airway remodeling by directly interacting with TGF-beta3. Collectively,
      these findings revealed that Lyn regulates TGF-beta3 isoform and modulates the
      development of airway remodeling, which may have therapeutic implications for
      severe chronic asthma. 

PMID- 24127554
TI  - Disparate epitopes mediating protective heterologous immunity to unrelated
      viruses share peptide-MHC structural features recognized by cross-reactive T
      cells.
AB  - Closely related peptide epitopes can be recognized by the same T cells and
      contribute to the immune response against pathogens encoding those epitopes, but
      sometimes cross-reactive epitopes share little homology. The degree of structural
      homology required for such disparate ligands to be recognized by cross-reactive
      TCRs remains unclear. In this study, we examined the mechanistic basis for cross
      reactive T cell responses between epitopes from unrelated and pathogenic viruses,
      lymphocytic choriomeningitis virus (LCMV) and vaccinia virus. Our results show
      that the LCMV cross-reactive T cell response toward vaccinia virus is dominated
      by a shared asparagine residue, together with other shared structural elements
      conserved in the crystal structures of K(b)-VV-A11R and K(b)-LCMV-gp34. Based on
      analysis of the crystal structures and the specificity determinants for the cross
      reactive T cell response, we were able to manipulate the degree of cross
      reactivity of the T cell response, and to predict and generate a LCMV cross
      reactive response toward a variant of a null OVA-derived peptide. These results
      indicate that protective heterologous immune responses can occur for disparate
      epitopes from unrelated viruses. 

PMID- 24127556
TI  - Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen
      cross-presentation and robust type I IFN secretion.
AB  - Plasmacytoid dendritic cells (pDCs) play a crucial role in initiating immune
      responses by secreting large amounts of type I IFNs. Currently, the role for
      human pDCs as professional APCs in the cross-presentation of exogenous Ags is
      being re-evaluated. Human pDCs are equipped with a broad repertoire of Ag uptake
      receptors and an efficient Ag-processing machinery. In this study, we set out to
      investigate which receptor can best be deployed to deliver Ag to pDCs for Ag
      (cross-)presentation. We show that targeting nanoparticles to pDCs via the C-type
      lectins DEC-205, DC immunoreceptor, blood DC Ag-2, or the FcR CD32 led to uptake,
      processing, and (cross-) presentation of encapsulated Ag to both CD4(+) and
      CD8(+) T cells. This makes these receptors good candidates for potential in vivo
      targeting of pDCs by nanocarriers. Notably, the coencapsulated TLR7 agonist R848
      efficiently activated pDCs, resulting in phenotypical maturation as well as
      robust IFN-alpha and TNF-alpha production. Taken together, their cross
      presentation capacity and type I IFN production to further activate components of
      both the innate and adaptive immune system mark pDCs as inducers of potent
      antitumor responses. These findings pave the way to actively recruit human pDCs
      for cellular cancer immunotherapy. 

PMID- 24127555
TI  - Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor
      KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses.
AB  - KIR2DL4 (CD158d) is a distinct member of the killer cell Ig-like receptor (KIR)
      family in human NK cells that can induce cytokine production and cytolytic
      activity in resting NK cells. Soluble HLA-G, normally expressed only by fetal
      derived trophoblast cells, was reported to be a ligand for KIR2DL4; however,
      KIR2DL4 expression is not restricted to the placenta and can be found in
      CD56(high) subset of peripheral blood NK cells. We demonstrated that KIR2DL4 can
      interact with alternative ligand(s), expressed by cells of epithelial or
      fibroblast origin. A genome-wide high-throughput siRNA screen revealed that
      KIR2DL4 recognition of cell-surface ligand(s) is directly regulated by heparan
      sulfate (HS) glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1). KIR2DL4 was found
      to directly interact with HS/heparin, and the D0 domain of KIR2DL4 was essential
      for this interaction. Accordingly, exogenous HS/heparin can regulate cytokine
      production by KIR2DL4-expressing NK cells and HEK293T cells (HEK293T-2DL4), and
      induces differential localization of KIR2DL4 to rab5(+) and rab7(+) endosomes,
      thus leading to downregulation of cytokine production and degradation of the
      receptor. Furthermore, we showed that intimate interaction of syndecan-4 (SDC4)
      HS proteoglycan (HSPG) and KIR2DL4 directly affects receptor endocytosis and
      membrane trafficking. 

PMID- 24127557
TI  - Reduced T cell-dependent humoral immune response in microsomal prostaglandin E
      synthase-1 null mice is mediated by nonhematopoietic cells.
AB  - Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that specifically
      catalyzes the conversion of PGH2 to PGE2. We showed that mPGES-1 null mice had a
      significantly reduced incidence and severity of collagen-induced arthritis
      compared with wild-type (WT) mice associated with a marked reduction in Abs to
      type II collagen. In this study, we further elucidated the role of mPGES-1 in the
      humoral immune response. Basal levels of serum IgM and IgG were significantly
      reduced in mPGES-1 null mice. Compared with WT mice, mPGES-1 null mice exhibited
      a significant reduction of hapten-specific serum Abs in response to immunization
      with the T cell-dependent (TD) Ag DNP-keyhole limpet hemocyanin. Immunization
      with the T cell-independent type 1 Ag trinitrophenyl-LPS or the T cell
      independent type 2 Ag DNP-Ficoll revealed minimal differences between strains.
      Germinal center formation in the spleen of mPGES-1 null and WT mice were similar
      after immunization with DNP-keyhole limpet hemocyanin. To determine whether the
      effect of mPGES-1 and PGE2 was localized to hematopoietic or nonhematopoietic
      cells, we generated bone marrow chimeras. We demonstrated that mPGES-1 deficiency
      in nonhematopoietic cells was the critical factor for reduced TD Ab production.
      We conclude that mPGES-1 and PGE2-dependent phenotypic changes of
      nonhematopoietic/mesenchymal stromal cells play a key role in TD humoral immune
      responses in vivo. These findings may have relevance to the pathogenesis of
      rheumatoid arthritis and other autoimmune inflammatory diseases associated with
      autoantibody formation. 

PMID- 24127558
TI  - Cooperativity of CD44 and CD49d in leukemia cell homing, migration, and survival
      offers a means for therapeutic attack.
AB  - A CD44 blockade drives leukemic cells into differentiation and apoptosis by
      dislodging from the osteogenic niche. Because anti-CD49d also supports
      hematopoietic stem cell mobilization, we sought to determine the therapeutic
      efficacy of a joint CD49d/CD44 blockade. To unravel the underlying mechanism, the
      CD49d(-) EL4 lymphoma was transfected with CD49d or point-mutated CD49d,
      prohibiting phosphorylation and FAK binding; additionally, a CD44(-) Jurkat
      subline was transfected with murine CD44, CD44 with a point mutation in the ezrin
      binding site, or with cytoplasmic tail-truncated CD44. Parental and transfected
      EL4 and Jurkat cells were evaluated for adhesion, migration, and apoptosis
      susceptibility in vitro and in vivo. Ligand-binding and Ab-blocking studies
      revealed CD44-CD49d cooperation in vitro and in vivo in adhesion, migration, and
      apoptosis resistance. The cooperation depends on ligand-induced proximity such
      that both CD44 and CD49d get access to src, FAK, and paxillin and via lck to the
      MAPK pathway, with the latter also supporting antiapoptotic molecule liberation.
      Accordingly, synergisms were only seen in leukemia cells expressing wild-type
      CD44 and CD49d. Anti-CD44 together with anti-CD49d efficiently dislodged EL4
      CD49d/Jurkat-CD44 in bone marrow and spleen. Dislodging was accompanied by
      increased apoptosis susceptibility that strengthened low-dose chemotherapy, the
      combined treatment most strongly interfering with metastatic settlement and being
      partly curative. Ab treatment also promoted NK and Ab-dependent cellular
      cytotoxicity activation, which affected leukemia cells independent of CD44/CD49d
      tail mutations. Thus, mostly owing to a blockade of joint signaling, anti-CD44
      and anti-CD49d hamper leukemic cell settlement and break apoptosis resistance,
      which strongly supports low-dose chemotherapy. 

PMID- 24127561
TI  - Sequence analysis of hepatitis C virus from patients with relapse after a
      sustained virological response: relapse or reinfection?
AB  - BACKGROUND: A sustained virological response (SVR) is the major end point of
      therapy for chronic hepatitis C virus (HCV) infection. Late relapse of infection
      is rare and poorly characterized. Three of 103 patients with a SVR treated at the
      National Institutes of Health had late relapse. We evaluated HCV RNA sequences in
      serum and liver tissue to distinguish relapse from reinfection. METHODS: Per
      patient, 10-22 clones of amplified 5' untranslated region were evaluated in
      pretreatment and relapse serum specimens and in liver biopsy specimens obtained
      during SVR. Genotypes and sequence diversity were evaluated. Four patients whose
      infection relapsed before they reached a SVR (ie, the early relapse group) were
      used as a comparison. RESULTS: Results of tests for detection of serum HCV RNA in
      all patients with late relapse were repeatedly negative during the first 24 weeks
      after therapy but became positive 8, 75, and 78 months after SVR. Reinfection
      risk factors were absent in 2 of 3 patients. In all patients with early or late
      relapse, apart from minor variations, the original HCV sequence was present
      before treatment and after relapse. All liver biopsy specimens from patients with
      late relapse were HCV RNA positive at SVR, with sequences nearly identical to
      those of specimens obtained at other time points. CONCLUSIONS: Sequence
      comparisons suggest that reappearance of HCV RNA years after a SVR can be from
      relapse of the initial viral infection rather than reinfection from a different
      virus.

PMID- 24127562
TI  - Hepatitis C virus infection: when is a cure not a cure?

PMID- 24127563
TI  - Using High-Fidelity Simulation to Develop Nurse-Physician Teams.

PMID- 24127564
TI  - A cell-body groove housing the new flagellum tip suggests an adaptation of
      cellular morphogenesis for parasitism in the bloodstream form of Trypanosoma
      brucei.
AB  - Flagella are highly conserved organelles present in a wide variety of species. In
      Trypanosoma brucei the single flagellum is necessary for morphogenesis, cell
      motility and pathogenesis, and is attached along the cell body. A new flagellum
      is formed alongside the old during the cell division cycle. In the (insect)
      procyclic form, the flagella connector (FC) attaches the tip of the new flagellum
      to the side of the old flagellum, ensuring faithful replication of cell
      architecture. The FC is not present in the bloodstream form of the parasite. We
      show here, using new imaging techniques including serial block-face scanning
      electron microscopy (SBF-SEM), that the distal tip of the new flagellum in the
      bloodstream form is embedded within an invagination in the cell body plasma
      membrane, named the groove. We suggest that the groove has a similar function to
      the flagella connector. The groove is a mobile junction located alongside the
      microtubule quartet (MtQ) and occurred within a gap in the subpellicular
      microtubule corset, causing significant modification of microtubules during
      elongation of the new flagellum. It appears likely that this novel form of
      morphogenetic structure has evolved to withstand the hostile immune response in
      the mammalian blood.

PMID- 24127565
TI  - Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated
      keratinocytes.
AB  - Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the
      development of skin cancer. To elucidate the initial signaling during UV-induced
      damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis
      induction. UVA, but not UVB, induced plasma membrane damage, which was repaired
      by Ca(2+)-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in
      extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two
      hours after UVA irradiation, we detected activation of caspase-8, which was
      reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and
      apoptosis was reduced by prevention of endocytosis and by the use of cathepsin
      inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte
      response to UVA and is followed by cathepsin-dependent activation of caspase-8.
      The findings have implications for the understanding of UV-induced skin damage
      and emphasize that UVA and UVB initiate apoptosis through different signaling
      pathways in keratinocytes.

PMID- 24127566
TI  - Phosphorylation of moesin by Jun N-terminal kinase is important for podosome
      rosette formation in Src-transformed fibroblasts.
AB  - Podosomes are actin-based membrane protrusions that facilitate extracellular
      matrix degradation and motility of invasive cells. Podosomes can self-organize
      into large rosette-like structures in Src-transformed fibroblasts, osteoclasts
      and some highly invasive cancer cells. However, the mechanism of this assembly
      remains obscure. In this study, we show that the suppression of Jun N-terminal
      kinase (JNK) by the JNK inhibitor SP600125 or short-hairpin RNA inhibited
      podosome rosette formation in SrcY527F-transformed NIH3T3 fibroblasts. In
      addition, SrcY527F was less able to induce podosome rosettes in JNK1-null or JNK2
      null mouse embryo fibroblasts than in wild-type counterparts. The kinase activity
      of JNK was essential for promoting podosome rosette formation but not for its
      localization to podosome rosettes. Moesin, a member of the ERM (ezrin, radixin
      and moesin) protein family, was identified as a substrate of JNK. We show that
      the phosphorylation of moesin at Thr558 by JNK was important for podosome rosette
      formation in SrcY527F-transformed NIH3T3 fibroblasts. Taken together, our results
      unveil a novel role of JNK in podosome rosette formation through the
      phosphorylation of moesin.

PMID- 24127568
TI  - Oncogene PKCepsilon controls INrf2-Nrf2 interaction in normal and cancer cells
      through phosphorylation of INrf2.
AB  - The INrf2 (Keap1)-Nrf2 cell sensor complex has a crucial role in protection
      against chemical- and radiation-induced oxidative stress and cellular
      transformation. INrf2, in association with Cul3-Rbx1, ubiquitylates and degrades
      Nrf2. Exposure to stressors leads to stabilization of Nrf2 and the coordinated
      activation of cytoprotective proteins and cellular protection. However, the
      molecular signal(s) that regulate control of Nrf2 by INrf2 remain elusive. In
      this report, we demonstrate that phosphorylation of INrf2 at Ser599 and Ser602 by
      the oncoprotein PKCepsilon is essential for INrf2-Nrf2 interaction, and the
      subsequent ubiquitylation and degradation of Nrf2. Inhibition of PKCepsilon,
      knockdown of PKCepsilon and the INrf2S602A mutant all failed to phosphorylate
      INrf2, leading to loss of the INrf2-Nrf2 interaction, Nrf2 degradation and
      enhanced cytoprotection and drug resistance. Molecular modeling analyses revealed
      that phosphorylation of S599 exposes the deeply buried S602 for phosphorylation
      and enhanced INrf2-Nrf2 interaction. Analysis of human lung and liver tumor
      protein arrays showed lower PKCepsilon and higher Nrf2 levels, which presumably
      promoted cancer cell survival and drug resistance. In conclusion, phosphorylation
      of INrf2 by PKCepsilon leads to regulation of Nrf2, with significant implications
      for the survival of cancer cells, which often express lower levels of PKCepsilon.

PMID- 24127567
TI  - Insulin receptor isoform switching in intestinal stem cells, progenitors,
      differentiated lineages and tumors: evidence that IR-B limits proliferation.
AB  - Despite evidence for the impact of insulin on intestinal epithelial physiology
      and pathophysiology, the expression patterns, roles, and regulation of insulin
      receptor (IR) and IR isoforms in the intestinal epithelium are not well
      characterized. IR-A is thought to mediate the proliferative effects of insulin or
      insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be
      the metabolic receptor for insulin in specialized tissues. This study used a
      novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial
      stem cells (IESCs), progenitors, enteroendocrine cells and differentiated
      lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human
      intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that
      there is differential expression of IR-A or IR-B in stem and tumor cells versus
      differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell
      proliferation. Our findings provide evidence that IR-B expression is
      significantly lower in highly proliferative IESCs and progenitor cells versus
      post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus
      differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly
      tumorigenic CRC cells. These differences in IR-B were accompanied by altered
      levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR
      alternative splicing. Forced IR-B expression in subconfluent and undifferentiated
      Caco-2 cells reduced proliferation and increased biomarkers of differentiation.
      Our findings indicate that the impact of insulin on different cell types in the
      intestinal epithelium might differ depending on relative IR-B IR-A expression
      levels and provide new evidence for the roles of IR-B to limit proliferation of
      CRC cells.

PMID- 24127569
TI  - Characterisation of Weibel-Palade body fusion by amperometry in endothelial cells
      reveals fusion pore dynamics and the effect of cholesterol on exocytosis.
AB  - Regulated secretion from endothelial cells is mediated by Weibel-Palade body
      (WPB) exocytosis. Plasma membrane cholesterol is implicated in regulating
      secretory granule exocytosis and fusion pore dynamics; however, its role in
      modulating WPB exocytosis is not clear. To address this we combined high
      resolution electrochemical analysis of WPB fusion pore dynamics, by amperometry,
      with high-speed optical imaging of WPB exocytosis following cholesterol depletion
      or supplementation in human umbilical vein endothelial cells. We identified
      serotonin (5-HT) immunoreactivity in WPBs, and VMAT1 expression allowing
      detection of secreted 5-HT as discrete current spikes during exocytosis. A high
      proportion of spikes (~75%) had pre-spike foot signals, indicating that WPB
      fusion proceeds via an initial narrow pore. Cholesterol depletion significantly
      reduced pre-spike foot signal duration and increased the rate of fusion pore
      expansion, whereas cholesterol supplementation had broadly the reverse effect.
      Cholesterol depletion slowed the onset of hormone-evoked WPB exocytosis, whereas
      its supplementation increased the rate of WPB exocytosis and hormone-evoked
      proregion secretion. Our results provide the first analysis of WPB fusion pore
      dynamics and highlight an important role for cholesterol in the regulation of WPB
      exocytosis. 

PMID- 24127570
TI  - Crystal structures of an archaeal oligosaccharyltransferase provide insights into
      the catalytic cycle of N-linked protein glycosylation.
AB  - Oligosaccharyltransferase transfers an oligosaccharide chain to the asparagine
      residues in proteins. The archaeal and eubacterial oligosaccharyltransferases are
      single subunit membrane enzymes, referred to as "AglB" (archaeal glycosylation B)
      and "PglB" (protein glycosylation B), respectively. Only one crystal structure of
      a full-length PglB has been solved. Here we report the crystal structures of the
      full-length AglB from a hyperthermophilic archaeon, Archaeoglobus fulgidus. The
      AglB and PglB proteins share the common overall topology of the 13 transmembrane
      helices, and a characteristic long plastic loop in the transmembrane region. This
      is the structural basis for the formation of the catalytic center, consisting of
      conserved acidic residues coordinating a divalent metal ion. In one crystal form,
      a sulfate ion was bound next to the metal ion. This structure appears to
      represent a dolichol-phosphate binding state, and suggests the release mechanism
      for the glycosylated product. The structure in the other crystal form corresponds
      to the resting state conformation with the well-ordered plastic loop in the
      transmembrane region. The overall structural similarity between the distantly
      related AglB and PglB proteins strongly indicates the conserved catalytic
      mechanism in the eukaryotic counterpart, the STT3 (stauroporine and temperature
      sensitivity 3) protein. The detailed structural comparison provided the dynamic
      view of the N-glycosylation reaction, involving the conversion between the
      structured and unstructured states of the plastic loop in the transmembrane
      region and the formation and collapse of the Ser/Thr-binding pocket in the C
      terminal globular domain. 

PMID- 24127571
TI  - Testing the cation-hydration effect on the crystallization of Ca-Mg-CO3 systems.
AB  - Dolomite and magnesite are simple anhydrous calcium and/or magnesium carbonate
      minerals occurring mostly at Earth surfaces. However, laboratory synthesis of
      neither species at ambient temperature and pressure conditions has been proven
      practically possible, and the lack of success was assumed to be related to the
      strong solvation shells of magnesium ions in aqueous media. Here, we report the
      synthesis of MgCO3 and MgxCa(1-x)CO3 (0 < x < 1) solid phases at ambient
      conditions in the absence of water. Experiments were carried out in dry organic
      solvent, and the results showed that, although anhydrous phases were readily
      precipitated in the water-free environment, the precipitates' crystallinity was
      highly dependent on the Mg molar percentage content in the solution. In specific,
      magnesian calcite dominated in low [Mg(2+)]/[Ca(2+)] solutions but gave way to
      exclusive formation of amorphous MgxCa(1-x)CO3 and MgCO3 in high
      [Mg(2+)]/[Ca(2+)] and pure-Mg solutions. At conditions of [Mg(2+)]/[Ca(2+)] = 1,
      both nanocrystals of Ca-rich protodolomite and amorphous phase of Mg-rich MgxCa(1
      x)CO3 were formed. These findings exposed a previously unrecognized intrinsic
      barrier for Mg(2+) and CO3(2-) to develop long-range orders at ambient conditions
      and suggested that the long-held belief of cation-hydration inhibition on
      dolomite and magnesite mineralization needed to be reevaluated. Our study
      provides significant insight into the long-standing "dolomite problem" in
      geochemistry and mineralogy and may promote a better understanding of the
      fundamental chemistry in biomineralization and mineral-carbonation processes. 

PMID- 24127572
TI  - Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells,
      evoking antitumor immune responses in humans.
AB  - CD4(+) Treg cells expressing the transcription factor FOXP3 (forkhead box P3) are
      abundant in tumor tissues and appear to hinder the induction of effective
      antitumor immunity. A substantial number of T cells, including Treg cells, in
      tumor tissues and peripheral blood express C-C chemokine receptor 4 (CCR4). Here
      we show that CCR4 was specifically expressed by a subset of terminally
      differentiated and most suppressive CD45RA(-)FOXP3(hi)CD4(+) Treg cells
      [designated effector Treg (eTreg) cells], but not by CD45RA(+)FOXP3(lo)CD4(+)
      naive Treg cells, in peripheral blood of healthy individuals and cancer patients.
      In melanoma tissues, CCR4(+) eTreg cells were predominant among tumor
      infiltrating FOXP3(+) T cells and much higher in frequency compared with those in
      peripheral blood. With peripheral blood lymphocytes from healthy individuals and
      melanoma patients, ex vivo depletion of CCR4(+) T cells and subsequent in vitro
      stimulation of the depleted cell population with the cancer/testis antigen NY-ESO
      1 efficiently induced NY-ESO-1-specific CD4(+) T cells. Nondepletion failed in
      the induction. The magnitude of the responses was comparable with total removal
      of FOXP3(+) Treg cells by CD25(+) T-cell depletion. CCR4(+) T-cell depletion also
      augmented in vitro induction of NY-ESO-1-specific CD8(+) T cells in melanoma
      patients. Furthermore, in vivo administration of anti-CCR4 mAb markedly reduced
      the eTreg-cell fraction and augmented NY-ESO-1-specific CD8(+) T-cell responses
      in an adult T-cell leukemia-lymphoma patient whose leukemic cells expressed NY
      ESO-1. Collectively, these findings indicate that anti-CCR4 mAb treatment is
      instrumental for evoking and augmenting antitumor immunity in cancer patients by
      selectively depleting eTreg cells. 

PMID- 24127573
TI  - DNA-uptake machinery of naturally competent Vibrio cholerae.
AB  - Natural competence for transformation is a mode of horizontal gene transfer that
      is commonly used by bacteria to take up DNA from their environment. As part of
      this developmental program, so-called competence genes, which encode the
      components of a DNA-uptake machinery, are expressed. Several models have been
      proposed for the DNA-uptake complexes of competent bacteria, and most include a
      type IV (pseudo)pilus as a core component. However, cell-biology-based approaches
      to visualizing competence proteins have so far been restricted to Gram-positive
      bacteria. Here, we report the visualization of a competence-induced pilus in the
      Gram-negative bacterium Vibrio cholerae. We show that piliated cells mostly
      contain a single pilus that is not biased toward a polar localization and that
      this pilus colocalizes with the outer membrane secretin PilQ. PilQ, on the other
      hand, forms several foci around the cell and occasionally colocalizes with the
      dynamic cytoplasmic-traffic ATPase PilB, which is required for pilus extension.
      We also determined the minimum competence regulon of V. cholerae, which includes
      at least 19 genes. Bacteria with mutations in those genes were characterized with
      respect to the presence of surface-exposed pili, DNA uptake, and natural
      transformability. Based on these phenotypes, we propose that DNA uptake in
      naturally competent V. cholerae cells occurs in at least two steps: a pilus
      dependent translocation of the incoming DNA across the outer membrane and a pilus
      independent shuttling of the DNA through the periplasm and into the cytoplasm. 

PMID- 24127574
TI  - Crystal structure of Bacillus subtilis GabR, an autorepressor and transcriptional
      activator of gabT.
AB  - Bacillus subtilis GabR is a transcription factor that regulates gamma
      aminobutyric acid (GABA) metabolism. GabR is a member of the understudied
      MocR/GabR subfamily of the GntR family of transcription regulators. A typical
      MocR/GabR-type regulator is a chimeric protein containing a short N-terminal
      helix-turn-helix DNA-binding domain and a long C-terminal pyridoxal 5'-phosphate
      (PLP)-binding putative aminotransferase domain. In the presence of PLP and GABA,
      GabR activates the gabTD operon, which allows the bacterium to use GABA as
      nitrogen and carbon sources. GabR binds to its own promoter and represses gabR
      transcription in the absence of GABA. Here, we report two crystal structures of
      full-length GabR from B. subtilis: a 2.7-A structure of GabR with PLP bound and
      the 2.55-A apo structure of GabR without PLP. The quaternary structure of GabR is
      a head-to-tail domain-swap homodimer. Each monomer comprises two domains: an N
      terminal winged-helix DNA-binding domain and a C-terminal PLP-binding type I
      aminotransferase-like domain. The winged-helix domain contains putative DNA
      binding residues conserved in other GntR-type regulators. Together with
      sedimentation velocity and fluorescence polarization assays, the crystal
      structure of GabR provides insights into DNA binding by GabR at the gabR and gabT
      promoters. The absence of GabR-mediated aminotransferase activity in the presence
      of GABA and PLP, and the presence of an active site configuration that is
      incompatible with stabilization of the GABA external aldimine suggest that a GabR
      aminotransferase-like activity involving GABA and PLP is not essential to its
      primary function as a transcription regulator. 

PMID- 24127575
TI  - Reduced choice-related activity and correlated noise accompany perceptual
      deficits following unilateral vestibular lesion.
AB  - Signals from the bilateral vestibular labyrinths work in tandem to generate
      robust estimates of our motion and orientation in the world. The relative
      contributions of each labyrinth to behavior, as well as how the brain recovers
      after unilateral peripheral damage, have been characterized for motor reflexes,
      but never for perceptual functions. Here we measure perceptual deficits in a
      heading discrimination task following surgical ablation of the neurosensory
      epithelium in one labyrinth. We found large increases in heading discrimination
      thresholds and large perceptual biases at 1 wk postlesion. Repeated testing
      thereafter improved heading perception, but vestibular discrimination thresholds
      remained elevated 3 mo postlesion. Electrophysiological recordings from the
      contralateral vestibular and cerebellar nuclei revealed elevated neuronal
      discrimination thresholds, elevated neurometric-to-psychometric threshold ratios,
      and reduced trial-by-trial correlations with perceptual decisions ["choice
      probabilities" (CPs)]. The relationship between CP and neuronal threshold was
      shallower, but not significantly altered, suggesting that smaller CPs in lesioned
      animals could be largely attributable to greater neuronal thresholds.
      Simultaneous recordings from pairs of neurons revealed that correlated noise
      among neurons was also reduced following the lesion. Simulations of a simple
      pooling model, which takes into account the observed changes in tuning slope and
      correlated noise, qualitatively accounts for the elevated psychophysical
      thresholds and neurometric-to-psychometric ratios, as well as the decreased CPs.
      Thus, cross-labyrinthine interactions appear to play important roles in enhancing
      neuronal and perceptual sensitivity, strengthening interneuronal correlations,
      and facilitating correlations between neural activity and perceptual decisions. 

PMID- 24127576
TI  - Essential role for mammalian apurinic/apyrimidinic (AP) endonuclease Ape1/Ref-1
      in telomere maintenance.
AB  - The major mammalian apurinic/apyrimidinic endonuclease Ape1 is a multifunctional
      protein operating in protection of cells from oxidative stress via its DNA
      repair, redox, and transcription regulatory activities. The importance of Ape1
      has been marked by previous work demonstrating its requirement for viability in
      mammalian cells. However, beyond a requirement for Ape1-dependent DNA repair
      activity, deeper molecular mechanisms of the fundamental role of Ape1 in cell
      survival have not been defined. Here, we report that Ape1 is an essential factor
      stabilizing telomeric DNA, and its deficiency is associated with telomere
      dysfunction and segregation defects in immortalized cells maintaining telomeres
      by either the alternative lengthening of telomeres pathway (U2OS) or telomerase
      expression (BJ-hTERT), or in normal human fibroblasts (IMR90). Through the
      expression of Ape1 derivatives with site-specific changes, we found that the DNA
      repair and N-terminal acetylation domains are required for the Ape1 function at
      telomeres. Ape1 associates with telomere proteins in U2OS cells, and Ape1
      depletion causes dissociation of TRF2 protein from telomeres. Consistent with
      this effect, we also observed that Ape1 depletion caused telomere shortening in
      both BJ-hTERT and in HeLa cells. Thus, our study describes a unique and
      unpredicted role for Ape1 in telomere protection, providing a direct link between
      base excision DNA repair activities and telomere metabolism. 

PMID- 24127577
TI  - Hemoglobin-derived porphyrins preserved in a Middle Eocene blood-engorged
      mosquito.
AB  - Although hematophagy is found in ~14,000 species of extant insects, the fossil
      record of blood-feeding insects is extremely poor and largely confined to
      specimens identified as hematophagic based on their taxonomic affinities with
      extant hematophagic insects; direct evidence of hematophagy is limited to four
      insect fossils in which trypanosomes and the malarial protozoan Plasmodium have
      been found. Here, we describe a blood-engorged mosquito from the Middle Eocene
      Kishenehn Formation in Montana. This unique specimen provided the opportunity to
      ask whether or not hemoglobin, or biomolecules derived from hemoglobin, were
      preserved in the fossilized blood meal. The abdomen of the fossil mosquito was
      shown to contain very high levels of iron, and mass spectrometry data provided a
      convincing identification of porphyrin molecules derived from the oxygen-carrying
      heme moiety of hemoglobin. These data confirm the existence of taphonomic
      conditions conducive to the preservation of biomolecules through deep time and
      support previous reports of the existence of heme-derived porphyrins in
      terrestrial fossils.

PMID- 24127578
TI  - Placebo improves pleasure and pain through opposite modulation of sensory
      processing.
AB  - Placebo analgesia is often conceptualized as a reward mechanism. However, by
      targeting only negative experiences, such as pain, placebo research may tell only
      half the story. We compared placebo improvement of painful touch (analgesia) with
      placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a
      crossover design. Somatosensory processing was decreased during placebo analgesia
      and increased during placebo hyperhedonia. Both placebo responses were associated
      with similar patterns of activation increase in circuitry involved in emotion
      appraisal, including the pregenual anterior cingulate, medial orbitofrontal
      cortex, amygdala, accumbens, and midbrain structures. Importantly, placebo
      induced coupling between the ventromedial prefrontal cortex and periaqueductal
      gray correlated with somatosensory decreases to painful touch and somatosensory
      increases to pleasant touch. These findings suggest that placebo analgesia and
      hyperhedonia are mediated by activation of shared emotion appraisal
      neurocircuitry, which down- or up-regulates early sensory processing, depending
      on whether the expectation is reduced pain or increased pleasure. 

PMID- 24127579
TI  - Loss of estrogen-related receptor alpha promotes hepatocarcinogenesis development
      via metabolic and inflammatory disturbances.
AB  - Estrogen-related receptor alpha (ERRalpha) is a key regulator of mitochondrial
      function and metabolism essential for energy-driven cellular processes in both
      normal and cancer cells. ERRalpha has also been shown to mediate bone-derived
      macrophage activation by proinflammatory cytokines. However, the role of ERRalpha
      in cancer in which inflammation acts as a tumor promoter has yet to be
      investigated. Herein we show that global loss of ERRalpha accelerates the
      development of diethylnitrosamine (DEN)-induced hepatocellular carcinoma.
      Biochemical and metabolomics studies revealed that loss of ERRalpha promotes
      hepatocyte necrosis over apoptosis in response to DEN due to a deficiency in
      energy production. We further show that increased hepatocyte death and associated
      compensatory proliferation observed in DEN-injured ERRalpha-null livers is
      concomitant with increased nuclear factor kappaB (NF-kappaB)-dependent
      transcriptional control of cytokine expression in Kupffer cells. In particular,
      we demonstrate that loss of ERRalpha-dependent regulation of the NF-kappaB
      inhibitor IkappaBalpha leads to enhanced NF-kappaB activity and cytokine gene
      activation. Our work thus shows that global loss of ERRalpha activity promotes
      hepatocellular carcinoma by independent but synergistic mechanisms in hepatocytes
      and Kupffer cells, implying that pharmacological manipulation of ERRalpha
      activity may have a significant clinical impact on carcinogen-induced cancers. 

PMID- 24127580
TI  - MDMX contains an autoinhibitory sequence element.
AB  - MDM2 and MDMX are homologous proteins that bind to p53 and regulate its activity.
      Both contain three folded domains and ~70% intrinsically disordered regions.
      Previous detailed structural and biophysical studies have concentrated on the
      isolated folded domains. The N-terminal domains of both exhibit high affinity for
      the disordered N-terminal of p53 (p53TAD) and inhibit its transactivation
      function. Here, we have studied full-length MDMX and found a ~100-fold weaker
      affinity for p53TAD than does its isolated N-terminal domain. We found from NMR
      spectroscopy and binding studies that MDMX (but not MDM2) contains a conserved,
      disordered self-inhibitory element that competes intramolecularly for binding
      with p53TAD. This motif, which we call the WWW element, is centered around
      residues Trp200 and Trp201. Deletion or mutation of the element increased binding
      affinity of MDMX to that of the isolated N-terminal domain level. The self
      inhibition of MDMX implies a regulatory, allosteric mechanism of its activity.
      MDMX rests in a latent state in which its binding activity with p53TAD is masked
      by autoinhibition. Activation of MDMX would require binding to a regulatory
      protein. The inhibitory function of the WWW element may explain the oncogenic
      effects of an alternative splicing variant of MDMX that does not contain the WWW
      element and is found in some aggressive cancers.

PMID- 24127581
TI  - DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a
      unique mechanism.
AB  - DIM (3,3'-diindolylmethane), a small molecule compound, is a proposed cancer
      preventive agent that can be safely administered to humans in repeated doses. We
      report that administration of DIM in a multidose schedule protected rodents
      against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing
      was initiated before or up to 24 h after radiation. Physiologic submicromolar
      concentrations of DIM protected cultured cells against radiation by a unique
      mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a
      nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress.
      Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM
      induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced
      ATM signaling and NF-kappaB activation. DIM also caused activation of ATM in
      rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of
      protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not
      protect human breast cancer xenograft tumors against radiation under the
      conditions tested. In tumors, ATM was constitutively phosphorylated and was not
      further stimulated by radiation and/or DIM. Our findings suggest that DIM is a
      potent radioprotector and mitigator that functions by stimulating an ATM-driven
      DDR-like response and NF-kappaB survival signaling. 

PMID- 24127582
TI  - Direct transfer of graphene onto flexible substrates.
AB  - In this paper we explore the direct transfer via lamination of chemical vapor
      deposition graphene onto different flexible substrates. The transfer method
      investigated here is fast, simple, and does not require an intermediate transfer
      membrane, such as polymethylmethacrylate, which needs to be removed afterward.
      Various substrates of general interest in research and industry were studied in
      this work, including polytetrafluoroethylene filter membranes, PVC, cellulose
      nitrate/cellulose acetate filter membranes, polycarbonate, paraffin, polyethylene
      terephthalate, paper, and cloth. By comparing the properties of these substrates,
      two critical factors to ensure a successful transfer on bare substrates were
      identified: the substrate's hydrophobicity and good contact between the substrate
      and graphene. For substrates that do not satisfy those requirements,
      polymethylmethacrylate can be used as a surface modifier or glue to ensure
      successful transfer. Our results can be applied to facilitate current processes
      and open up directions for applications of chemical vapor deposition graphene on
      flexible substrates. A broad range of applications can be envisioned, including
      fabrication of graphene devices for opto/organic electronics, graphene membranes
      for gas/liquid separation, and ubiquitous electronics with graphene. 

PMID- 24127583
TI  - Differentiated kidney epithelial cells repair injured proximal tubule.
AB  - Whether kidney proximal tubule harbors a scattered population of epithelial stem
      cells is a major unsolved question. Lineage-tracing studies, histologic
      characterization, and ex vivo functional analysis results conflict. To address
      this controversy, we analyzed the lineage and clonal behavior of fully
      differentiated proximal tubule epithelial cells after injury. A CreER(T2)
      cassette was knocked into the sodium-dependent inorganic phosphate transporter
      SLC34a1 locus, which is expressed only in differentiated proximal tubule.
      Tamoxifen-dependent recombination was absolutely specific to proximal tubule.
      Clonal analysis after injury and repair showed that the bulk of labeled cells
      proliferate after injury with increased clone size after severe compared with
      mild injury. Injury to labeled proximal tubule epithelia induced expression of
      CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative
      epithelial stem cells in the human kidney. Similar results were observed in
      cultured proximal tubules, in which labeled clones proliferated and expressed
      dedifferentiation and injury markers. When mice with completely labeled kidneys
      were subject to injury and repair there was no dilution of fate marker despite
      substantial proliferation, indicating that unlabeled progenitors do not
      contribute to kidney repair. During nephrogenesis and early kidney growth, single
      proximal tubule clones expanded, suggesting that differentiated cells also
      contribute to tubule elongation. These findings provide no evidence for an
      intratubular stem-cell population, but rather indicate that terminally
      differentiated epithelia reexpress apparent stem-cell markers during injury
      induced dedifferentiation and repair. 

PMID- 24127584
TI  - A Drosophila model of closed head traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a substantial health issue worldwide, yet the
      mechanisms responsible for its complex spectrum of pathologies remains largely
      unknown. To investigate the mechanisms underlying TBI pathologies, we developed a
      model of TBI in Drosophila melanogaster. The model allows us to take advantage of
      the wealth of experimental tools available in flies. Closed head TBI was
      inflicted with a mechanical device that subjects flies to rapid acceleration and
      deceleration. Similar to humans with TBI, flies with TBI exhibited temporary
      incapacitation, ataxia, activation of the innate immune response,
      neurodegeneration, and death. Our data indicate that TBI results in death shortly
      after a primary injury only if the injury exceeds a certain threshold and that
      age and genetic background, but not sex, substantially affect this threshold.
      Furthermore, this threshold also appears to be dependent on the same cellular and
      molecular mechanisms that control normal longevity. This study demonstrates the
      potential of flies for providing key insights into human TBI that may ultimately
      provide unique opportunities for therapeutic intervention. 

PMID- 24127585
TI  - Crystal structure of a glucose/H+ symporter and its mechanism of action.
AB  - Glucose transporters are required to bring glucose into cells, where it is an
      essential energy source and precursor in protein and lipid synthesis. These
      transporters are involved in important common diseases such as cancer and
      diabetes. Here, we report the crystal structure of the Staphylococcus epidermidis
      glucose/H(+) symporter in an inward-facing conformation at 3.2-A resolution. The
      Staphylococcus epidermidis glucose/H(+) symporter is homologous to human glucose
      transporters, is very specific and has high avidity for glucose, and is inhibited
      by the human glucose transport inhibitors cytochalasin B, phloretin, and
      forskolin. On the basis of the crystal structure in conjunction with mutagenesis
      and functional studies, we propose a mechanism for glucose/H(+) symport and
      discuss the symport mechanism versus facilitated diffusion. 

PMID- 24127586
TI  - Putative megaenzyme DWA1 plays essential roles in drought resistance by
      regulating stress-induced wax deposition in rice.
AB  - Drought stress is a major limiting factor for crop production. Cuticular wax
      plays an important role in preventing water loss from drought stress. However,
      the genetic control of cuticular wax deposition under drought stress conditions
      has not been characterized. Here, we identified a rice gene Drought-Induced Wax
      Accumulation 1 (DWA1) encoding a very large protein (2,391 aa in length)
      containing multiple enzymatic structures, including an oxidoreductase-like
      domain; a prokaryotic nonribosomal peptide synthetase-like module, including an
      AMP-binding domain; and an allene oxide synthase-like domain. This previously
      unreported putative megaenzyme is conserved in vascular plants. A dwa1 KO mutant
      was highly sensitive to drought stress relative to the WT. DWA1 was
      preferentially expressed in vascular tissues and epidermal layers and strongly
      induced by drought stress. The dwa1 mutant was impaired in cuticular wax
      accumulation under drought stress, which significantly altered the cuticular wax
      composition of the plant, resulting in increased drought sensitivity. The mutant
      had reduced levels of very-long-chain fatty acids, and plants overexpressing DWA1
      showed elevated levels of very-long-chain fatty acids relative to the WT. The
      expression of many wax-related genes was significantly suppressed in dwa1 under
      drought conditions. The AMP-binding domain exhibited in vitro enzymatic activity
      in activating long-chain fatty acids to form acyl-CoA. Our results suggest that
      DWA1 controls drought resistance by regulating drought-induced cuticular wax
      deposition in rice. This finding may have significant implications for improving
      the drought resistance of crop varieties. 

PMID- 24127587
TI  - A test of Darwin's naturalization hypothesis in the thistle tribe shows that
      close relatives make bad neighbors.
AB  - Invasive species have great ecological and economic impacts and are difficult to
      control once established, making the ability to understand and predict invasive
      behavior highly desirable. Preemptive measures to prevent potential invasive
      species from reaching new habitats are the most economically and environmentally
      efficient form of management. Darwin's naturalization hypothesis predicts that
      invaders less related to native flora are more likely to be successful than those
      that are closely related to natives. Here we test this hypothesis, using the weed
      rich thistle tribe, Cardueae, in the California Floristic Province, a
      biodiversity hotspot, as our study system. An exhaustive molecular phylogenetic
      approach was used, generating and examining more than 100,000 likely phylogenies
      of the tribe based on nuclear and chloroplast DNA markers, representing the most
      in-depth reconstruction of the clade to date. Branch lengths separating invasive
      and noninvasive introduced taxa from native California taxa were used to
      represent phylogenetic distances between these groups and were compared at
      multiple biogeographical scales to ascertain whether invasive thistles are more
      or less closely related to natives than noninvasive introduced thistles are.
      Patterns within this highly supported clade show that not only are introduced
      thistles more closely related to natives more likely to be invasive, but these
      invasive species are also evolutionarily closer to native flora than by chance.
      This suggests that preadaptive traits are important in determining an invader's
      success. Such rigorous molecular phylogenetic analyses may prove a fruitful means
      for furthering our understanding of biological invasions and developing
      predictive frameworks for screening potential invasive taxa. 

PMID- 24127588
TI  - Musical agency reduces perceived exertion during strenuous physical performance.
AB  - Music is known to be capable of reducing perceived exertion during strenuous
      physical activity. The current interpretation of this modulating effect of music
      is that music may be perceived as a diversion from unpleasant proprioceptive
      sensations that go along with exhaustion. Here we investigated the effects of
      music on perceived exertion during a physically strenuous task, varying musical
      agency, a task that relies on the experience of body proprioception, rather than
      simply diverting from it. For this we measured psychologically indicated exertion
      during physical workout with and without musical agency while simultaneously
      acquiring metabolic values with spirometry. Results showed that musical agency
      significantly decreased perceived exertion during workout, indicating that
      musical agency may actually facilitate physically strenuous activities. This
      indicates that the positive effect of music on perceived exertion cannot always
      be explained by an effect of diversion from proprioceptive feedback. Furthermore,
      this finding suggests that the down-modulating effect of musical agency on
      perceived exertion may be a previously unacknowledged driving force for the
      development of music in humans: making music makes strenuous physical activities
      less exhausting. 

PMID- 24127589
TI  - Bispecific small molecule-antibody conjugate targeting prostate cancer.
AB  - Bispecific antibodies, which simultaneously target CD3 on T cells and tumor
      associated antigens to recruit cytotoxic T cells to cancer cells, are a promising
      new approach to the treatment of hormone-refractory prostate cancer. Here we
      report a site-specific, semisynthetic method for the production of bispecific
      antibody-like therapeutics in which a derivative of the prostate-specific
      membrane antigen-binding small molecule DUPA was selectively conjugated to a
      mutant alphaCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine,
      at a defined site. Homogeneous conjugates were generated in excellent yields and
      had good solubility. The efficacy of the conjugate was optimized by modifying the
      linker structure, relative binding orientation, and stoichiometry of the ligand.
      The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100
      pM), good serum half-life, and potent in vivo activity in prophylactic and
      treatment xenograft mouse models. This semisynthetic approach is likely to be
      applicable to the generation of additional bispecific agents using drug-like
      ligands selective for other cell-surface receptors.

PMID- 24127590
TI  - A naturally occurring insertion of a single amino acid rewires transcriptional
      regulation by glucocorticoid receptor isoforms.
AB  - In addition to guiding proteins to defined genomic loci, DNA can act as an
      allosteric ligand that influences protein structure and activity. Here we
      compared genome-wide binding, transcriptional regulation, and, using NMR, the
      conformation of two glucocorticoid receptor (GR) isoforms that differ by a single
      amino acid insertion in the lever arm, a domain that adopts DNA sequence-specific
      conformations. We show that these isoforms differentially regulate gene
      expression levels through two mechanisms: differential DNA binding and altered
      communication between GR domains. Our studies suggest a versatile role for DNA in
      both modulating GR activity and also in directing the use of GR isoforms. We
      propose that the lever arm is a "fulcrum" for bidirectional allosteric signaling,
      conferring conformational changes in the DNA reading head that influence DNA
      sequence selectivity, as well as conferring changes in the dimerization domain
      that connect functionally with remote regulatory surfaces, thereby influencing
      which genes are regulated and the magnitude of their regulation. 

PMID- 24127591
TI  - Chromatin stretch enhancer states drive cell-specific gene regulation and harbor
      human disease risk variants.
AB  - Chromatin-based functional genomic analyses and genomewide association studies
      (GWASs) together implicate enhancers as critical elements influencing gene
      expression and risk for common diseases. Here, we performed systematic chromatin
      and transcriptome profiling in human pancreatic islets. Integrated analysis of
      islet data with those from nine cell types identified specific and significant
      enrichment of type 2 diabetes and related quantitative trait GWAS variants in
      islet enhancers. Our integrated chromatin maps reveal that most enhancers are
      short (median = 0.8 kb). Each cell type also contains a substantial number of
      more extended (>= 3 kb) enhancers. Interestingly, these stretch enhancers are
      often tissue-specific and overlap locus control regions, suggesting that they are
      important chromatin regulatory beacons. Indeed, we show that (i) tissue
      specificity of enhancers and nearby gene expression increase with enhancer
      length; (ii) neighborhoods containing stretch enhancers are enriched for
      important cell type-specific genes; and (iii) GWAS variants associated with
      traits relevant to a particular cell type are more enriched in stretch enhancers
      compared with short enhancers. Reporter constructs containing stretch enhancer
      sequences exhibited tissue-specific activity in cell culture experiments and in
      transgenic mice. These results suggest that stretch enhancers are critical
      chromatin elements for coordinating cell type-specific regulatory programs and
      that sequence variation in stretch enhancers affects risk of major common human
      diseases.

PMID- 24127592
TI  - Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host
      lipid composition.
AB  - In the representative gut bacterium Lactobacillus plantarum, we identified genes
      encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty
      acids and revealed in detail the metabolic pathway that generates hydroxy fatty
      acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans
      fatty acids as intermediates. Furthermore, we observed these intermediates,
      especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids
      were much higher in specific pathogen-free mice than in germ-free mice,
      indicating that these fatty acids are generated through polyunsaturated fatty
      acids metabolism of gastrointestinal microorganisms. These findings suggested
      that lipid metabolism by gastrointestinal microbes affects the health of the host
      by modifying fatty acid composition. 

PMID- 24127593
TI  - Cytosolic reducing power preserves glutamate in retina.
AB  - Glutamate in neurons is an important excitatory neurotransmitter, but it also is
      a key metabolite. We investigated how glutamate in a neural tissue is protected
      from catabolism. Flux analysis using (13)C-labeled fuels revealed that retinas
      use activities of the malate aspartate shuttle to protect >98% of their glutamate
      from oxidation in mitochondria. Isolation of glutamate from the oxidative pathway
      relies on cytosolic NADH/NAD(+), which is influenced by extracellular glucose,
      lactate, and pyruvate. 

PMID- 24127594
TI  - Reward-based hypertension control by a synthetic brain-dopamine interface.
AB  - Synthetic biology has significantly advanced the design of synthetic trigger
      controlled devices that can reprogram mammalian cells to interface with complex
      metabolic activities. In the brain, the neurotransmitter dopamine coordinates
      communication with target neurons via a set of dopamine receptors that control
      behavior associated with reward-driven learning. This dopamine transmission has
      recently been suggested to increase central sympathetic outflow, resulting in
      plasma dopamine levels that correlate with corresponding brain activities. By
      functionally rewiring the human dopamine receptor D1 (DRD1) via the second
      messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing
      cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator
      modules, we have designed a synthetic dopamine-sensitive transcription controller
      that reversibly fine-tunes specific target gene expression at physiologically
      relevant brain-derived plasma dopamine levels. Following implantation of circuit
      transgenic human cell lines insulated by semipermeable immunoprotective
      microcontainers into mice, the designer device interfaced with dopamine-specific
      brain activities and produced a systemic expression response when the animal's
      reward system was stimulated by food, sexual arousal, or addictive drugs. Reward
      triggered brain activities were able to remotely program peripheral therapeutic
      implants to produce sufficient amounts of the atrial natriuretic peptide, which
      reduced the blood pressure of hypertensive mice to the normal physiologic range.
      Seamless control of therapeutic transgenes by subconscious behavior may provide
      opportunities for treatment strategies of the future. 

PMID- 24127595
TI  - Restoring the sense of touch with a prosthetic hand through a brain interface.
AB  - Our ability to manipulate objects dexterously relies fundamentally on sensory
      signals originating from the hand. To restore motor function with upper-limb
      neuroprostheses requires that somatosensory feedback be provided to the
      tetraplegic patient or amputee. Given the complexity of state-of-the-art
      prosthetic limbs and, thus, the huge state space they can traverse, it is
      desirable to minimize the need for the patient to learn associations between
      events impinging on the limb and arbitrary sensations. Accordingly, we have
      developed approaches to intuitively convey sensory information that is critical
      for object manipulation--information about contact location, pressure, and timing
      -through intracortical microstimulation of primary somatosensory cortex. In
      experiments with nonhuman primates, we show that we can elicit percepts that are
      projected to a localized patch of skin and that track the pressure exerted on the
      skin. In a real-time application, we demonstrate that animals can perform a
      tactile discrimination task equally well whether mechanical stimuli are delivered
      to their native fingers or to a prosthetic one. Finally, we propose that the
      timing of contact events can be signaled through phasic intracortical
      microstimulation at the onset and offset of object contact that mimics the
      ubiquitous on and off responses observed in primary somatosensory cortex to
      complement slowly varying pressure-related feedback. We anticipate that the
      proposed biomimetic feedback will considerably increase the dexterity and
      embodiment of upper-limb neuroprostheses and will constitute an important step in
      restoring touch to individuals who have lost it.

PMID- 24127596
TI  - Structural basis for KIT receptor tyrosine kinase inhibition by antibodies
      targeting the D4 membrane-proximal region.
AB  - Somatic oncogenic mutations in the receptor tyrosine kinase KIT function as major
      drivers of gastrointestinal stromal tumors and a subset of acute myeloid
      leukemia, melanoma, and other cancers. Although treatment of these cancers with
      tyrosine kinase inhibitors shows dramatic responses and durable disease control,
      drug resistance followed by clinical progression of disease eventually occurs in
      virtually all patients. In this report, we describe inhibitory KIT antibodies
      that bind to the membrane-proximal Ig-like D4 of KIT with significant overlap
      with an epitope in D4 that mediates homotypic interactions essential for KIT
      activation. Crystal structures of the anti-KIT antibody in complex with KIT D4
      and D5 allowed design of affinity-matured libraries that were used to isolate
      variants with increased affinity and efficacy. Isolated antibodies showed KIT
      inhibition together with suppression of cell proliferation driven by ligand
      stimulated WT or constitutively activated oncogenic KIT mutant. These antibodies
      represent a unique therapeutic approach and a step toward the development of
      "naked" or toxin-conjugated KIT antibodies for the treatment of KIT-driven
      cancers. 

PMID- 24127597
TI  - Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation
      after RNA virus infection.
AB  - Nod-like receptor family, pyrin domain-containing 3 (NLRP3), is involved in the
      early stages of the inflammatory response by sensing cellular damage or distress
      due to viral or bacterial infection. Activation of NLRP3 triggers its assembly
      into a multimolecular protein complex, termed "NLRP3 inflammasome." This event
      leads to the activation of the downstream molecule caspase-1 that cleaves the
      precursor forms of proinflammatory cytokines, such as interleukin 1 beta (IL
      1beta) and IL-18, and initiates the immune response. Recent studies indicate that
      the reactive oxygen species produced by mitochondrial respiration is critical for
      the activation of the NLRP3 inflammasome by monosodium urate, alum, and ATP.
      However, the precise mechanism by which RNA viruses activate the NLRP3
      inflammasome is not well understood. Here, we show that loss of mitochondrial
      membrane potential [DeltaPsi(m)] dramatically reduced IL-1beta secretion after
      infection with influenza, measles, or encephalomyocarditis virus (EMCV). Reduced
      IL-1beta secretion was also observed following overexpression of the
      mitochondrial inner membrane protein, uncoupling protein-2, which induces
      mitochondrial proton leakage and dissipates DeltaPsi(m). DeltaPsi(m) was required
      for association between the NLRP3 and mitofusin 2, a mediator of mitochondrial
      fusion, after infection with influenza virus or EMCV. Importantly, the knockdown
      of mitofusin 2 significantly reduced the secretion of IL-1beta after infection
      with influenza virus or EMCV. Our results provide insight into the roles of
      mitochondria in NLRP3 inflammasome activation. 

PMID- 24127598
TI  - Observation of orientation-dependent electron transfer in molecule-surface
      collisions.
AB  - Molecules typically must point in specific relative directions to participate
      efficiently in energy transfer and reactions. For example, Forster energy
      transfer favors specific relative directions of each molecule's transition dipole
      [Forster T (1948) Ann Phys 2(1-2):55-75] and electron transfer between gas-phase
      molecules often depends on the relative orientation of orbitals [Brooks PR, et
      al. (2007) J Am Chem Soc 129(50):15572-15580]. Surface chemical reactions can be
      many orders of magnitude faster than their gas-phase analogs, a fact that
      underscores the importance of surfaces for catalysis. One reason surface
      reactions can be so fast is the labile change of oxidation state that commonly
      takes place upon adsorption, a process involving electron transfer between a
      solid metal and an approaching molecule. By transferring electrons to or from the
      adsorbate, the process of bond weakening and/or cleavage is initiated, chemically
      activating the reactant [Yoon B, et al. (2005) Science 307(5708):403-407]. Here,
      we show that the vibrational relaxation of NO--an example of electronically
      nonadiabatic energy transfer that is driven by an electron transfer event [Gadzuk
      JW (1983) J Chem Phys 79(12):6341-6348]--is dramatically enhanced when the
      molecule approaches an Au(111) surface with the N atom oriented toward the
      surface. This represents a rare opportunity to investigate the steric influences
      on an electron transfer reaction happening at a surface.

PMID- 24127600
TI  - Development of socio-emotional competence in bonobos.
AB  - Social and emotional skills are tightly interlinked in human development, and
      both are negatively impacted by disrupted social development. The same interplay
      between social and emotional skills, including expressions of empathy, has
      received scant attention in other primates however, despite the growing interest
      in caring, friendships, and the fitness benefits of social skills. Here we
      examine the development of socio-emotional competence in juvenile bonobos (Pan
      paniscus) at a sanctuary in the Democratic Republic of the Congo, focusing on the
      interplay between various skills, including empathy-related responding. Most
      subjects were rehabilitated orphans, but some were born at the sanctuary and
      mother-reared there. We observed how juveniles with different rearing backgrounds
      responded to stressful events, both when the stress affected themselves (e.g., a
      lost fight) or others (e.g., witnessing the distress of others). The main
      dependent variable was the consolation of distressed parties by means of calming
      body contact. As in children, consolation was predicted by overall social
      competence and effective emotion regulation, as reflected in the speed of
      recovery from self-distress and behavioral measures of anxiety. Juveniles more
      effective at self-regulation were more likely to console others in distress, and
      such behavior was more typical of mother-reared juveniles than orphans. These
      results highlight the interplay between the development of social and emotional
      skills in our ape relatives and the importance of the mother-offspring bond in
      shaping socio-emotional competence. 

PMID- 24127599
TI  - Dynamic model for the coordination of two enhancers of broad by EGFR signaling.
AB  - Although it is widely appreciated that a typical developmental control gene is
      regulated by multiple enhancers, coordination of enhancer activities remains
      poorly understood. We propose a mechanism for such coordination in Drosophila
      oogenesis, when the expression of the transcription factor Broad (BR) evolves
      from a uniform to a two-domain pattern that prefigures the formation of two
      respiratory eggshell appendages. This change reflects sequential activities of
      two enhancers of the br gene, early and late, both of which are controlled by the
      epidermal growth factor receptor (EGFR) pathway. The late enhancer controls br in
      the appendage-producing cells, but the function of the early enhancer remained
      unclear. We found that the early enhancer is essential for the activity of the
      late enhancer and induction of eggshell appendages. This requirement can be
      explained by a mechanism whereby the BR protein produced by the early enhancer
      protects the late enhancer from EGFR-dependent repression. We illustrate this
      complex mechanism using a computational model that correctly predicts the wild
      type dynamics of BR expression and its response to genetic perturbations. 

PMID- 24127601
TI  - ELL, a novel TFIIH partner, is involved in transcription restart after DNA
      repair.
AB  - DNA lesions that block transcription may cause cell death even when repaired, if
      transcription does not restart to reestablish cellular metabolism. However,
      transcription resumption after individual DNA-lesion repair remains poorly
      described in mechanistic terms and its players are largely unknown. The general
      transcription factor II H (TFIIH) is a major actor of both nucleotide excision
      repair subpathways of which transcription-coupled repair highlights the interplay
      between DNA repair and transcription. Using an unbiased proteomic approach, we
      have identified the protein eleven-nineteen lysine-rich leukemia (ELL) as a TFIIH
      partner. Here we show that ELL is recruited to UV-damaged chromatin in a Cdk7-
      dependent manner (a component of the cyclin-dependent activating kinase
      subcomplex of TFIIH). We demonstrate that depletion of ELL strongly hinders RNA
      polymerase II (RNA Pol II) transcription resumption after lesion removal and DNA
      gap filling. Lack of ELL was also observed to increase RNA Pol II retention to
      the chromatin during this process. Identifying ELL as an essential player for RNA
      Pol II restart during cellular DNA damage response opens the way to obtaining a
      mechanistic description of transcription resumption after DNA repair. 

PMID- 24127602
TI  - Nitric oxide mediates local activity-dependent excitatory synapse development.
AB  - Learning related paradigms play an important role in shaping the development and
      specificity of synaptic networks, notably by regulating mechanisms of spine
      growth and pruning. The molecular events underlying these synaptic rearrangements
      remain poorly understood. Here we identify NO signaling as a key mediator of
      activity-dependent excitatory synapse development. We find that chronic blockade
      of NO production in vitro and in vivo interferes with the development of
      hippocampal and cortical excitatory spine synapses. The effect results from a
      selective loss of activity-mediated spine growth mechanisms and is associated
      with morphological and functional alterations of remaining synapses. These
      effects of NO are mediated by a cGMP cascade and can be reproduced or prevented
      by postsynaptic expression of vasodilator-stimulated phosphoprotein phospho
      mimetic or phospho-resistant mutants. In vivo analyses show that absence of NO
      prevents the increase in excitatory synapse density induced by environmental
      enrichment and interferes with the formation of local clusters of excitatory
      synapses. We conclude that NO plays an important role in regulating the
      development of excitatory synapses by promoting local activity-dependent spine
      growth mechanisms. 

PMID- 24127603
TI  - Catalytically powered dynamic assembly of rod-shaped nanomotors and passive
      tracer particles.
AB  - Nano- and microscale motors powered by catalytic reactions exhibit collective
      behavior such as swarming, predator-prey interactions, and chemotaxis that
      resemble those of biological microorganisms. A quantitative understanding of the
      catalytically generated forces between particles that lead to these behaviors has
      so far been lacking. Observations and numerical simulations of pairwise
      interactions between gold-platinum nanorods in hydrogen peroxide solutions show
      that attractive and repulsive interactions arise from the catalytically generated
      electric field. Electrokinetic effects drive the assembly of staggered doublets
      and triplets of nanorods that are moving in the same direction. None of these
      behaviors are observed with nanorods composed of a single metal. The motors also
      collect tracer microparticles at their head or tail, depending on the charge of
      the particles, actively assembling them into close-packed rafts and aggregates of
      rafts. These motor-tracer particle interactions can also be understood in terms
      of the catalytically generated electric field around the ends of the nanorod
      motors. 

PMID- 24127604
TI  - Single-molecule imaging of the functional crosstalk between surface NMDA and
      dopamine D1 receptors.
AB  - Dopamine is a powerful modulator of glutamatergic neurotransmission and NMDA
      receptor-dependent synaptic plasticity. Although several intracellular cascades
      participating in this functional dialogue have been identified over the last few
      decades, the molecular crosstalk between surface dopamine and glutamate NMDA
      receptor (NMDAR) signaling still remains poorly understood. Using a combination
      of single-molecule detection imaging and electrophysiology in live hippocampal
      neurons, we demonstrate here that dopamine D1 receptors (D1Rs) and NMDARs form
      dynamic surface clusters in the vicinity of glutamate synapses. Strikingly, D1R
      activation or D1R/NMDAR direct interaction disruption decreases the size of these
      clusters, increases NMDAR synaptic content through a fast lateral redistribution
      of the receptors, and favors long-term synaptic potentiation. Together, these
      data demonstrate the presence of dynamic D1R/NMDAR perisynaptic reservoirs
      favoring a rapid and bidirectional surface crosstalk between receptors and set
      the plasma membrane as the primary stage of the dopamine-glutamate interplay. 

PMID- 24127606
TI  - BcsA and BcsB form the catalytically active core of bacterial cellulose synthase
      sufficient for in vitro cellulose synthesis.
AB  - Cellulose is a linear extracellular polysaccharide. It is synthesized by membrane
      embedded glycosyltransferases that processively polymerize UDP-activated glucose.
      Polymer synthesis is coupled to membrane translocation through a channel formed
      by the cellulose synthase. Although eukaryotic cellulose synthases function in
      macromolecular complexes containing several different enzyme isoforms,
      prokaryotic synthases associate with additional subunits to bridge the periplasm
      and the outer membrane. In bacteria, cellulose synthesis and translocation is
      catalyzed by the inner membrane-associated bacterial cellulose synthase (Bcs)A
      and BcsB subunits. Similar to alginate and poly-beta-1,6 N-acetylglucosamine,
      bacterial cellulose is implicated in the formation of sessile bacterial
      communities, termed biofilms, and its synthesis is likewise stimulated by cyclic
      di-GMP. Biochemical studies of exopolysaccharide synthesis are hampered by
      difficulties in purifying and reconstituting functional enzymes. We demonstrate
      robust in vitro cellulose synthesis reconstituted from purified BcsA and BcsB
      proteins from Rhodobacter sphaeroides. Although BcsA is the catalytically active
      subunit, the membrane-anchored BcsB subunit is essential for catalysis. The
      purified BcsA-B complex produces cellulose chains of a degree of polymerization
      in the range 200-300. Catalytic activity critically depends on the presence of
      the allosteric activator cyclic-di-GMP, but is independent of lipid-linked
      reactants. Our data reveal feedback inhibition of cellulose synthase by UDP but
      not by the accumulating cellulose polymer and highlight the strict substrate
      specificity of cellulose synthase for UDP-glucose. A truncation analysis of BcsB
      localizes the region required for activity of BcsA within its C-terminal membrane
      associated domain. The reconstituted reaction provides a foundation for the
      synthesis of biofilm exopolysaccharides, as well as its activation by cyclic-di
      GMP. 

PMID- 24127605
TI  - Tissue factor pathway inhibitor-alpha inhibits prothrombinase during the
      initiation of blood coagulation.
AB  - Tissue factor (TF) pathway inhibitor (TFPI) is a well-characterized activated
      factor X (FXa)-dependent inhibitor of TF-initiated coagulation produced in two
      alternatively spliced isoforms, TFPIalpha and TFPIbeta. The TFPIalpha C terminus
      has a basic sequence nearly identical to a portion of the factor V (FV) B domain
      necessary for maintaining FV in an inactive conformation via interaction with an
      acidic region of the B domain. We demonstrate rapid inhibition of prothrombinase
      by TFPIalpha mediated through a high-affinity exosite interaction between the
      basic region of TFPIalpha and the FV acidic region, which is retained in FXa
      activated FVa and platelet FVa. This inhibitory activity is not mediated by
      TFPIbeta and is lost upon removal of the acidic region of FVa by thrombin. The
      data identify a previously undescribed, isoform-specific anticoagulant function
      for TFPIalpha and are a unique description of physiologically relevant inhibition
      of prothrombinase. These findings, combined with previous descriptions of
      differential expression patterns of TFPIalpha and TFPIbeta in platelets and
      endothelial cells, suggest that the TFPI isoforms may act through distinct
      mechanisms to inhibit the initial stages of intravascular coagulation, with
      TFPIbeta acting to dampen TF expressed on the surface of vascular cells, whereas
      TFPIalpha dampens the initial prothrombinase formed on the activated platelet
      surface. 

PMID- 24127607
TI  - ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63.
AB  - Squamous cell carcinoma (SCC) is highly malignant and refractory to therapy. The
      majority of existing mouse SCC models involve multiple gene mutations. Very few
      mouse models of spontaneous SCC have been generated by a single gene deletion.
      Here we report a haploinsufficient SCC mouse model in which exon 3 of the Tp53BP2
      gene (a p53 binding protein) was deleted in one allele in a BALB/c genetic
      background. Tp53BP2 encodes ASPP2 (ankyrin repeats, SH3 domain and protein rich
      region containing protein 2). Keratinocyte differentiation induces ASPP2 and its
      expression is inversely correlated with p63 protein in vitro and in vivo. Up
      regulation of p63 expression is required for ASPP2(Deltaexon3/+) BALB/c mice to
      develop SCC, as heterozygosity of p63 but not p53 prevents them from developing
      it. Mechanistically, ASPP2 inhibits DeltaNp63 expression through its ability to
      bind IkappaB and enhance nuclear Rel/A p65, a component of the NF-kappaB
      transcription complex, which mediates the repression of p63. Reduced ASPP2
      expression associates with tumor metastasis and increased p63 expression in human
      head and neck SCCs. This study identifies ASPP2 as a tumor suppressor that
      suppresses SCC via inflammatory signaling through NF-kappaB-mediated repression
      of p63. 

PMID- 24127608
TI  - MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization
      by repressing the palmitoylation enzyme, DHHC9.
AB  - MicroRNA-134 (miR-134) serves as a widely accepted model for microRNA function in
      synaptic plasticity. In this model, synaptic activity stimulates miR-134
      expression, which then regulates dendrite growth and spine formation. By using a
      ratiometric microRNA sensor, we found, unexpectedly, that miR-134 activity in
      cortical neurons was restricted to interneurons. Using an assay designed to trap
      microRNA-mRNA complexes, we determined that miR-134 interacted directly with the
      mRNA encoding the palmitoylation enzyme, DHHC9. This enzyme is known to
      palmitoylate H-Ras, a modification required for proper membrane trafficking.
      Treatment with bicuculline, a GABAA receptor antagonist, decreased DHHC9
      expression in somatostatin-positive interneurons and membrane localization of an
      H-Ras reporter in a manner that depended on miR-134. Thus, although miR-134 has
      been proposed to affect all types of neurons, we showed that functionally active
      miR-134 is produced in only a selected population of neurons where it influences
      the expression of targets, such as DHHC9, that regulate membrane targeting of
      critical signaling molecules. 

PMID- 24127610
TI  - Corpus callosum fibre disruption in Marchiafava-Bignami disease.

PMID- 24127611
TI  - When a bruise is not just a bruise.

PMID- 24127609
TI  - PHYTOCHROME-DEPENDENT LATE-FLOWERING accelerates flowering through physical
      interactions with phytochrome B and CONSTANS.
AB  - In flowering plants, light is one of the major environmental stimuli that
      determine the timing of the transition from the vegetative to reproductive phase.
      In Arabidopsis, phytochrome B (phyB); phyA; cryptochrome 2; and flavin-binding,
      KELCH repeat, F-BOX 1 are major photoreceptors that regulate flowering. Unlike
      phyA; cryptochrome 2; and flavin-binding, KELCH repeat, F-BOX 1, phyB delays
      flowering mainly by destabilizing the CONSTANS (CO) protein, whose reduction
      leads to decreased expression of a florigen gene, flowering locus T. However, it
      remains unclear how the phyB-mediated CO destabilization is mechanistically
      regulated. Here, we identify a unique phytochrome-dependent late-flowering (PHL)
      gene, which is mainly involved in the phyB-dependent regulation of flowering.
      Plants with mutant phl exhibited a late-flowering phenotype, especially under
      long-day conditions. The late-flowering phenotype of the phl mutant was
      completely overridden by a phyB mutation, indicating that PHL normally
      accelerates flowering by countering the inhibitory effect of phyB on flowering.
      Accordingly, PHL physically interacted with phyB both in vitro and in vivo in a
      red light-dependent manner. Furthermore, in the presence of phyB under red light,
      PHL interacted with CO as well. Taken together, we propose that PHL regulates
      photoperiodic flowering by forming a phyB-PHL-CO tripartite complex.

PMID- 24127612
TI  - Veterans' health care considerations for today's nursing curricula.
AB  - Although there have been several wars and conflicts since World War I, the
      escalating numbers of veterans since that time is now evident. Extraordinary
      survival results have evolved from effective triage, trauma treatment, and
      recovery maneuvers during Operation Iraqi Freedom and Operation New Dawn (OIF) in
      Iraq and Operation Enduring Freedom (OEF) in Afghanistan. Yet even with those
      results, the number of physical and mentally wounded individuals exceeded 32,000
      from OIF and 16,000 from OEF. How will we help these service men and women meet
      the special challenges they may face after discharge from the military? This
      article presents a rationale for content integration, health concerns, and
      realistic educational suggestions for faculty as they prepare professional nurses
      to care for these veterans and their families. Future nurses need to be prepared
      to care for this patient population in community health care systems.

PMID- 24127614
TI  - Evaluation of a Workplace Bullying Cognitive Rehearsal Program in a Hospital
      Setting.

PMID- 24127613
TI  - Physiological differences during decision making between experienced nurses and
      nursing students: a pilot study.
AB  - The purpose of this quasi-experimental pilot study was to explore the difference
      in sympathetic activity between groups of experienced nurses and nursing students
      during a clinical scenario. Eleven female, senior-level nursing students and 10
      female nurses with more than 5 years of nursing experience participated in a
      computer-generated scenario, while simultaneously having their skin conductance
      recorded. Experienced nurses generated significantly more skin conductance
      responses than did the nursing students, and they had a higher score on the
      clinical scenario. The presence of a bodily signal was found to occur
      statistically more often in experienced nurses than in nursing students during
      clinical decision making, which has theoretical and practical implications for
      nurse educators who seek to aid students in developing sound decision making.

PMID- 24127615
TI  - A Multi-State Assessment of Employer-Sponsored Quality Improvement Education for
      Early-Career Registered Nurses.

PMID- 24127617
TI  - Optical determination of intracellular water in apoptotic cells.
AB  - Intracellular water plays a critical role in apoptotic and necrotic cell death.
      We describe a method for quantifying cell water by application of two previously
      described variants of transmission microscopy. By taking two axially displaced
      brightfield images, the phase shift of the transmitted wave was computed using
      the transport-of-intensity equation. At the same time, cell thickness was
      determined by transmission through an externally applied dye ('transmission
      through-dye' microscopy); switching between these two imaging modalities was
      accomplished by simply changing the illumination wavelength. The sets of data
      thus obtained allow computation of the refractive index and cell water content
      within individual cells. The method was illustrated using cells treated with
      apoptotic agents staurosporine and actinomycin D and with necrosis inducer
      ionomycin. Water imaging allows discrimination between apoptotic volume decrease
      due to dehydration from that due to detachment of apoptotic bodies and can be
      used on samples where cell volume determination alone would be difficult or
      insufficient.

PMID- 24127616
TI  - Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition.
AB  - A functional role of the cerebellar nodulus and ventral uvula (lobules X and
      IXc,d of the vermis) for vestibular processing has been strongly suggested by
      direct reciprocal connections with the vestibular nuclei, as well as direct
      vestibular afferent inputs as mossy fibres. Here we have explored the types of
      neurons in the macaque vestibular nuclei targeted by nodulus/ventral uvula
      inhibition using orthodromic identification from the caudal vermis. We found that
      all nodulus-target neurons are tuned to vestibular stimuli, and most are
      insensitive to eye movements. Such non-eye-movement neurons are thought to
      project to vestibulo-spinal and/or thalamo-cortical pathways. Less than 20% of
      nodulus-target neurons were sensitive to eye movements, suggesting that the
      caudal vermis can also directly influence vestibulo-ocular pathways. In general,
      response properties of nodulus-target neurons were diverse, spanning the whole
      continuum previously described in the vestibular nuclei. Most nodulus-target
      cells responded to both rotation and translation stimuli and only a few were
      selectively tuned to translation motion only. Other neurons were sensitive to net
      linear acceleration, similar to otolith afferents. These results demonstrate
      that, unlike the flocculus and ventral paraflocculus which target a particular
      cell group, nodulus/ventral uvula inhibition targets a large diversity of cell
      types in the vestibular nuclei, consistent with a broad functional significance
      contributing to vestibulo-ocular, vestibulo-thalamic and vestibulo-spinal
      pathways.

PMID- 24127618
TI  - Important considerations for protein analyses using antibody based techniques:
      down-sizing Western blotting up-sizes outcomes.
AB  - Western blotting has been used for protein analyses in a wide range of tissue
      samples for >30 years. Fundamental to Western blotting success are a number of
      important considerations, which unfortunately are often overlooked or not
      appreciated. Firstly, lowly expressed proteins may often be better detected by
      dramatically reducing the amount of sample loaded. Single cell (fibre) Western
      blotting demonstrates the ability to detect proteins in small sample sizes, 5-10
      MUg total mass (1-3 MUg total protein). That is an order of magnitude less than
      often used. Using heterogeneous skeletal muscle as the tissue of representation,
      the need to undertake Western blotting in sample sizes equivalent to single fibre
      segments is demonstrated. Secondly, incorrect results can be obtained if samples
      are fractionated and a proportion of the protein of interest inadvertently
      discarded during sample preparation. Thirdly, quantitative analyses demand that a
      calibration curve be used. This is regardless of using a loading control, which
      must be proven to not change with the intervention and also be appropriately
      calibrated. Fourthly, antibody specificity must be proven using whole tissue
      analyses, and for immunofluorescence analyses it is vital that only a single
      protein is detected. If appropriately undertaken, Western blotting is reliable,
      quantitative, both in relative and absolute terms, and extremely valuable.

PMID- 24127619
TI  - Endogenous and maximal sarcoplasmic reticulum calcium content and calsequestrin
      expression in type I and type II human skeletal muscle fibres.
AB  - The relationship between sarcoplasmic reticulum (SR) Ca(2+) content and
      calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre
      lysing assay was used to quantify the endogenous Ca(2+) content and maximal
      Ca(2+) capacity of the SR in skinned segments of type I and type II fibres from
      vastus lateralis muscles of young healthy adults. Western blotting of individual
      fibres showed the great majority contained either all fast or all slow isoforms
      of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that
      the strontium sensitivity of the force response was closely indicative of the
      troponin C isoform present. The endogenous SR Ca(2+) content was slightly lower
      in type I compared to type II fibres (0.76 +/- 0.03 and 0.85 +/- 0.02 mmol Ca(2+)
      per litre of fibre, respectively), with virtually all of this Ca(2+) evidently
      being in the SR, as it could be rapidly released with a caffeine-low [Mg(2+)]
      solution (only 0.08 +/- 0.01 and <0.07 mmol l(-1), respectively, remaining). The
      maximal Ca(2+) content that could be reached with SR Ca(2+) loading was 1.45 +/-
      0.04 and 1.79 +/- 0.03 mmol l(-1) in type I and type II fibres, respectively (P <
      0.05). In non-lysed skinned fibres, where the SR remained functional, repeated
      cycles of caffeine-induced Ca(2+) release and subsequent Ca(2+) reloading
      similarly indicated that (i) maximal SR Ca(2+) content was lower in type I fibres
      than in type II fibres (P < 0.05), and (ii) the endogenous Ca(2+) content
      represented a greater percentage of maximal content in type I fibres compared to
      type II fibres (~59% and 41%, respectively, P < 0.05). Type II fibres were found
      on average to contain ~3-fold more CSQ1 and ~5-fold less CSQ2 than type I fibres
      (P < 0.001). The findings are consistent with the SR Ca(2+) content
      characteristics in human type II fibres being primarily determined by the CSQ1
      abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2.

PMID- 24127623
TI  - Development of Simulated Chest Compression Videos for Objective Evaluation of CPR
      Instructors.

PMID- 24127620
TI  - Important role of mucosal serotonin in colonic propulsion and peristaltic
      reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1.
AB  - Although there is general agreement that mucosal 5-hydroxytryptamine (5-HT) can
      initiate peristaltic reflexes in the colon, recent studies have differed as to
      whether or not the role of mucosal 5-HT is critical. We therefore tested the
      hypothesis that the secretion of 5-HT from mucosal enterochromaffin (EC) cells is
      essential for the manifestation of murine colonic peristaltic reflexes. To do so,
      we analysed the mechanisms underlying faecal pellet propulsion in isolated colons
      of mice lacking tryptophan hydroxylase 1 (Tph1(-/-) mice), which is the rate
      limiting enzyme in the biosynthesis of mucosal but not neuronal 5-HT. We used
      video analysis of faecal pellet propulsion, tension transducers to record colonic
      migrating motor complexes (CMMCs) and intracellular microelectrodes to record
      circular muscle activity occurring spontaneously or following intraluminal
      distension. When compared with control (Tph1(+/+)) mice, Tph1(-/-) animals
      exhibited: (1) an elongated colon; (2) larger faecal pellets; (3) orthograde
      propulsion followed by retropulsion (not observed in Tph1(+/+) colon); (4) slower
      in vitro propulsion of larger faecal pellets (28% of Tph1(+/+)); (5) CMMCs that
      infrequently propagated in an oral to anal direction because of impaired
      descending inhibition; (6) reduced CMMCs and inhibitory responses to intraluminal
      balloon distension; (7) an absence of reflex activity in response to mucosal
      stimulation. In addition, (8) thin pellets that propagated along the control
      colon failed to do so in Tph1(-/-) colon; and (9) the 5-HT3 receptor antagonist
      ondansetron, which reduced CMMCs and blocked their propagation in Tph1(+/+) mice,
      failed to alter CMMCs in Tph1(-/-) animals. Our observations suggest that mucosal
      5-HT is essential for reflexes driven by mucosal stimulation and is also
      important for normal propagation of CMMCs and propulsion of pellets in the
      isolated colon.

PMID- 24127622
TI  - Randomized controlled trial of mindfulness-based stress reduction for
      prehypertension.
AB  - OBJECTIVE: Mindfulness-based stress reduction (MBSR) is an increasingly popular
      practice demonstrated to alleviate stress and treat certain health conditions.
      MBSR may reduce elevated blood pressure (BP). Treatment guidelines recommend life
      style modifications for BP in the prehypertensive range (systolic BP [SBP] 120
      139 mm Hg or diastolic BP [DBP] 80-89 mm Hg), followed by antihypertensives if BP
      reaches hypertensive levels. MBSR has not been thoroughly evaluated as a
      treatment of prehypertension. A randomized clinical trial of MBSR for high BP was
      conducted to determine whether BP reductions associated with MBSR exceed those
      observed for an active control condition consisting of progressive muscle
      relaxation (PMR) training. METHODS: Fifty-six men (43%) and women (57%) averaging
      (standard deviation) 50.3 (6.5) years of age (91% white) with unmedicated BP in
      the prehypertensive range were randomized to 8 weeks of MBSR or PMR delivered in
      a group format. Treatment sessions were administered by one treatment provider
      and lasted approximately 2.5 hours each week. Clinic BP was the primary outcome
      measure. Ambulatory BP was a secondary outcome measure. RESULTS: Analyses were
      based on intent to treat. Patients randomized to MBSR exhibited a 4.8-mm Hg
      reduction in clinic SBP, which was larger than the 0.7-mm Hg reduction observed
      for PMR (p = .016). Those randomized to MBSR exhibited a 1.9-mm Hg reduction in
      DBP compared with a 1.2-mm Hg increase for PMR (p = .008). MBSR did not result in
      larger decreases in ambulatory BP than in PMR. CONCLUSIONS: MBSR resulted in a
      reduction in clinic SBP and DBP compared with PMR. Trial Registration
      ClinicalTrials.gov identifier: NCT00440596.

PMID- 24127625
TI  - Reflecting on Research: Sharpening Nurses' Focus Through Engaged Learning.

PMID- 24127626
TI  - Educating Australian Registered Nurses in Comprehensive Health Assessment: A
      Pilot Study.

PMID- 24127627
TI  - Preparation of (-)-Nutlin-3 using enantioselective organocatalysis at decagram
      scale.
AB  - Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful
      platform for the development of cancer chemotherapeutics, stimulated by the
      Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with
      wild-type p53. The lack of efficient methods for the enantioselective synthesis
      of cis-imidazolines, however, has limited their more general use. Our disclosure
      of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to
      prepare larger amounts of this tool used widely in cancer biology. Key to the
      decagram-scale synthesis described here was the discovery of a novel bis(amidine)
      organocatalyst that provides high enantioselectivity at warmer reaction
      temperature (-20  degrees C) and low catalyst loadings. Further refinements to
      the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and
      elimination of all but three chromatographic purifications. 

PMID- 24127628
TI  - Spatially controlled photochemical peptide and polymer conjugation on
      biosurfaces.
AB  - An efficient phototriggered Diels-Alder conjugation is utilized to graft in an
      effective and straightforward approach poly(trifluoro ethyl methacrylate) (Mn =
      3700 Da, D = 1.27) and a model peptide (GIGKFLHS) onto thin hyaluronan films and
      cellulose surfaces. The surfaces were functionalized with an o-quinodimethane
      moiety - capable of releasing a caged diene - via carbodiimide mediated coupling.
      The o-quinodimethane group is employed as a photoactive linker to tether
      predefined peptide/polymer strands in a spatially controlled manner onto the
      biosurface by photoenol ligation. An in-depth characterization employing XPS, ToF
      SIMS, SPR, ellipsometry, and AFM was conducted to evidence the effectiveness of
      the presented approach. 

PMID- 24127630
TI  - Effect of magnesium on calcium and oxalate ion binding.
AB  - BACKGROUND AND PURPOSE: Magnesium (Mg(2+)) has been shown to be a kidney stone
      inhibitor; however, the exact mechanism of its effect is unknown. Using
      theoretical models, the interactions of calcium and oxalate were examined in the
      presence of Mg(2+). METHODS: Molecular dynamics simulations were performed with
      NAMD and CHARMM27 force field. The interaction between calcium (Ca(2+)) and
      oxalate (Ox(2-)) ions was examined with and without magnesium. Concentrations of
      calcium and oxalate were 0.1 M and 0.03 M, respectively, and placed in a cubic
      box of length ~115 Angstrom. Na(+) and Cl(-) ions were inserted to meet system
      electroneutrality. Mg(2+) was then placed into the box at physiologic
      concentrations and the interaction between calcium and oxalate was observed. In
      addition, the effect of citrate and pH were examined in regard to the effect of
      Mg(2+) inhibition. Each system was allowed to run until a stable crystalline
      structure was formed. RESULTS: The presence of Mg(2+) reduces the average size of
      the calcium oxalate and calcium phosphate aggregates. This effect is found to be
      Mg(2+) concentration-dependent. It is also found that Mg(2+) inhibition is
      synergistic with citrate and continues to be effective at acidic pH levels.
      CONCLUSION: The presence of magnesium ions tends to destabilize calcium oxalate
      ion pairs and reduce the size of their aggregates. Mg(2+) inhibitory effect is
      synergistic with citrate and remains effective in acidic environments. Further
      studies are needed to see if this can be applied to in vivo models as well as
      extending this to other stone inhibitors and promoters.

PMID- 24127631
TI  - Comparing radiation exposure between ablative therapies for small renal masses.
AB  - PURPOSE: The purpose of this study was to evaluate the amount of radiation
      exposure patients with small renal masses undergoing percutaneous cyroablation
      (PCA) or percutaneous radiofrequency ablation (PRFA) received during treatment
      and follow up. MATERIALS AND METHODS: A retrospective review was conducted on all
      patients with small renal masses <4 cm treated with PCA or PRFA over a 7-year
      period in a single academic center. Preoperative, operative, and post-operative
      variables were collected and compared. Radiation exposure received during
      treatment and 1 year of follow up were also determined for each modality.
      Statistical analysis was conducted using SPSS V.17 (SPSS, Chicago, IL). The
      groups were compared using the Mann-Whitney U and Pearson Chi-Square tests.
      Statistical significance was considered at p<0.05. RESULTS: There was no
      significant difference in pretreatment parameters or oncologic outcomes. The
      average PCA treatment radiation exposure was 39.7 mSv (15.5-133.4 mSv) compared
      with 22.2 mSv (8.1-67.7 mSv) for PRFA (p=0.001). During the initial year after
      treatment, the estimated mean treatment and follow-up radiation exposure for PCA
      was 134.5 mSv, compared with 117 mSv for RFA when routine computerized tomography
      imaging was employed. CONCLUSION: To our knowledge, this is the first published
      study that quantifies radiation exposure in PCA and PRFA treatment for small
      renal masses. These relatively high radiation exposures should be included in the
      informed consent for these procedures. In addition, caution should be employed
      when applying these technologies in young patients who are most susceptible to
      long-term radiation damage.

PMID- 24127632
TI  - Genomic signatures of BRCA1 but not BRCA2 associated high-grade serous carcinoma
      resemble basal-like breast cancer.

PMID- 24127633
TI  - Manipulating chiral transmission by gate geometry: switching in graphene with
      transmission gaps.
AB  - We explore the chiral transmission of electrons across graphene heterojunctions
      for electronic switching using gate geometry alone. A sequence of gates is used
      to collimate and orthogonalize the chiral transmission lobes across multiple
      junctions, resulting in negligible overall current. The resistance of the device
      is enhanced by several orders of magnitude by biasing the gates into the bipolar
      npn doping regime, even as the ON state in the homogeneous nnn regime remains
      highly conductive. The mobility is preserved because the switching involves the
      suppression of transmission over a range of energy (transmission gap) instead of
      a structural band gap that would reduce the number of available channels of
      conduction. Under a different biasing scheme (npn to npp), this transmission gap
      can be made highly gate tunable, allowing a subthermal turn-on that beats the
      Landauer bound on switching energy, limiting present-day digital electronics. 

PMID- 24127634
TI  - Unifying expression scale for peptide hydrophobicity in proteomic reversed phase
      high-pressure liquid chromatography experiments.
AB  - As an initial step in our efforts to unify the expression of peptide retention
      times in proteomic liquid chromatography-mass spectrometry (LC-MS) experiments,
      we aligned the chromatographic properties of a number of peptide retention
      standards against a collection of peptides commonly observed in proteomic
      experiments. The standard peptide mixtures and tryptic digests of samples of
      different origins were separated under the identical chromatographic condition
      most commonly employed in proteomics: 100 A C18 sorbent with 0.1% formic acid as
      an ion-pairing modifier. Following our original approach (Krokhin, O. V.; Spicer,
      V. Anal. Chem. 2009, 81, 9522-9530) the retention characteristics of these
      standards and collection of tryptic peptides were mapped into hydrophobicity
      index (HI) or acetonitrile percentage units. This scale allows for direct
      visualization of the chromatographic outcome of LC-MS acquisitions, monitors the
      performance of the gradient LC system, and simplifies method development and
      interlaboratory data alignment. Wide adoption of this approach would
      significantly aid understanding the basic principles of gradient peptide RP-HPLC
      and solidify our collective efforts in acquiring confident peptide retention
      libraries, a key component in the development of targeted proteomic approaches.

PMID- 24127635
TI  - Complementarity to an miRNA seed region is sufficient to induce moderate
      repression of a target transcript in the unicellular green alga Chlamydomonas
      reinhardtii.
AB  - MicroRNAs (miRNAs) are 20-24 nt non-coding RNAs that play important regulatory
      roles in a broad range of eukaryotes by pairing with mRNAs to direct post
      transcriptional repression. The mechanistic details of miRNA-mediated post
      transcriptional regulation have been well documented in multicellular model
      organisms. However, this process remains poorly studied in algae such as
      Chlamydomonas reinhardtii, and specific features of miRNA biogenesis, target mRNA
      recognition and subsequent silencing are not well understood. In this study, we
      report on the characterization of a Chlamydomonas miRNA, cre-miR1174.2, which is
      processed from a near-perfect hairpin RNA. Using Gaussia luciferase (gluc)
      reporter genes, we have demonstrated that cre-miR1174.2 is functional in
      Chlamydomonas and capable of triggering site-specific cleavage at the center of a
      perfectly complementary target sequence. A mismatch tolerance test assay, based
      on pools of transgenic strains, revealed that target hybridization to nucleotides
      of the seed region, at the 5' end of an miRNA, was sufficient to induce moderate
      repression of expression. In contrast, pairing to the 3' region of the miRNA was
      not critical for silencing. Our results suggest that the base-pairing
      requirements for small RNA-mediated repression in C. reinhardtii are more similar
      to those of metazoans compared with the extensive complementarity that is typical
      of land plants. Individual Chlamydomonas miRNAs may potentially modulate the
      expression of numerous endogenous targets as a result of these relaxed base
      pairing requirements.

PMID- 24127636
TI  - Latent class analysis of a series of 717 patients with vitiligo allows the
      identification of two clinical subtypes.
AB  - Non-segmental vitiligo (NSV) is an enigmatic disease with various clinical
      courses. To empirically identify underlying subtypes of NSV, we performed latent
      class analysis (LCA) of 717 consecutive patients with NSV seen between 2006 and
      2012 and were analyzed. Median age was 32 yrs (14-45), median age at NSV onset
      was 18 yrs (8-32), and median NSV duration 5 yrs (0.75-78.5). A two-class model
      showed the best fit. Of the 717 patients, 280 (39%) belonged to LC1 and 437 (61%)
      to LC2. LC1 patients had high probabilities for early disease onset (<12 yrs),
      halo nevi, family history of premature hair greying, Koebner phenomenon, previous
      episodes of repigmentation, and family history of vitiligo. By contrast, LC2
      patients were characterized by a late disease onset (after or at the age of 12
      yrs, median age of 30 yrs) and acrofacial localization without any lesions on
      trunk or limbs. These two LCA classes (LC1, 'prepubertal onset'; LC2, 'post
      pubertal onset') may help refining results from genome-wide association studies
      (GWAS) and allow a more accurate genotype-phenotype correlation and help defining
      more directed treatment protocols.

PMID- 24127637
TI  - Magnetic poles determinations and robustness of memory effect upon solubilization
      in a Dy(III)-based single ion magnet.
AB  - The [Dy(tta)3(L)] complex behaves as a single ion magnet both in its crystalline
      phase and in solution. Experimental and theoretical magnetic anisotropy axes
      perfectly match and lie along the most electro-negative atoms of the coordination
      sphere. Both VSM and MCD measurements highlight the robustness of the complex,
      with persistence of the memory effect even in solution up to 4 K. 

PMID- 24127638
TI  - Different neurodevelopmental symptoms have a common genetic etiology.
AB  - BACKGROUND: Although neurodevelopmental disorders are demarcated as discrete
      entities in the Diagnostic Statistical Manual of mental disorders, empirical
      evidence indicates that there is a high degree of overlap among them. The first
      aim of this investigation was to explore if a single general factor could account
      for the large degree of observed overlap among neurodevelopmental problems, and
      explore whether this potential factor was primarily genetic or environmental in
      origin. The second aim was to explore whether there was systematic covariation,
      either genetic or environmental, over and above that contributed by the potential
      general factor, unique to each syndrome. METHOD: Parents of all Swedish 9- and 12
      year-old twin pairs born between 1992 and 2002 were targeted for interview
      regarding problems typical of autism spectrum disorders, ADHD and other
      neurodevelopmental conditions (response rate: 80 percent). Structural equation
      modeling was conducted on 6,595 pairs to examine the genetic and environmental
      structure of 53 neurodevelopmental problems. RESULTS: One general genetic factor
      accounted for a large proportion of the phenotypic covariation among the 53
      symptoms. Three specific genetic subfactors identified 'impulsivity,' 'learning
      problems,' and 'tics and autism,' respectively. Three unique environment factors
      identified 'autism,' 'hyperactivity and impulsivity,' and 'inattention and
      learning problems,' respectively. CONCLUSION: One general genetic factor was
      responsible for the wide-spread phenotypic overlap among all neurodevelopmental
      symptoms, highlighting the importance of addressing broad patient needs rather
      than specific diagnoses. The unique genetic factors may help guide diagnostic
      nomenclature, whereas the unique environmental factors may highlight that
      neurodevelopmental symptoms are responsive to change at the individual level and
      may provide clues into different mechanisms and treatments. Future research would
      benefit from assessing the general factor separately from specific factors to
      better understand observed overlap among neurodevelopmental problems.

PMID- 24127639
TI  - Divergent metabolic responses of Apostichopus japonicus suffered from skin
      ulceration syndrome and pathogen challenge.
AB  - Skin ulceration syndrome (SUS) is the main limitation in the development of
      Apostichopus japonicus culture industries, in which Vibrio splendidus has been
      well documented as one of the major pathogens. However, the intrinsic mechanisms
      toward pathogen challenge and disease outbreak remain largely unknown at the
      metabolic level. In this work, the metabolic responses were investigated in
      muscles of sea cucumber among natural SUS-diseased and V. splendidus-challenged
      samples. The pathogen did not induce obvious biological effects in A. japonicus
      samples after infection for the first 24 h. An enhanced energy storage (or
      reduced energy demand) and immune responses were observed in V. splendidus
      challenged A. japonicus samples at 48 h, as marked by increased glucose and
      branched chain amino acids, respectively. Afterward, infection of V. splendidus
      induced significant increases in energy demand in A. japonicus samples at both 72
      and 96 h, confirmed by decreased glucose and glycogen, and increased ATP.
      Surprisingly, high levels of glycogen and glucose and low levels of threonine,
      alanine, arginine, glutamate, glutamine, taurine and ATP were founded in natural
      SUS-diseased sea cucumber. Our present results provided essential metabolic
      information about host-pathogen interaction for sea cucumber, and informed that
      the metabolic biomarkers induced by V. splendidus were not usable for the
      prediction of SUS disease in practice. 

PMID- 24127640
TI  - Understanding the role of different conductive polymers in improving the
      nanostructured sulfur cathode performance.
AB  - Lithium sulfur batteries have brought significant advancement to the current
      state-of-art battery technologies because of their high theoretical specific
      energy, but their wide-scale implementation has been impeded by a series of
      challenges, especially the dissolution of intermediate polysulfides species into
      the electrolyte. Conductive polymers in combination with nanostructured sulfur
      have attracted great interest as promising matrices for the confinement of
      lithium polysulfides. However, the roles of different conductive polymers on the
      electrochemical performances of sulfur electrode remain elusive and poorly
      understood due to the vastly different structural configurations of conductive
      polymer-sulfur composites employed in previous studies. In this work, we
      systematically investigate the influence of different conductive polymers on the
      sulfur cathode based on conductive polymer-coated hollow sulfur nanospheres with
      high uniformity. Three of the most well-known conductive polymers, polyaniline
      (PANI), polypyrrole (PPY), and poly(3,4-ethylenedioxythiophene) (PEDOT), were
      coated, respectively, onto monodisperse hollow sulfur nanopsheres through a
      facile, versatile, and scalable polymerization process. The sulfur cathodes made
      from these well-defined sulfur nanoparticles act as ideal platforms to study and
      compare how coating thickness, chemical bonding, and the conductivity of the
      polymers affected the sulfur cathode performances from both experimental
      observations and theoretical simulations. We found that the capability of these
      three polymers in improving long-term cycling stability and high-rate performance
      of the sulfur cathode decreased in the order of PEDOT > PPY > PANI. High specific
      capacities and excellent cycle life were demonstrated for sulfur cathodes made
      from these conductive polymer-coated hollow sulfur nanospheres. 

PMID- 24127641
TI  - Screening colonoscopy in HIV-infected patients: high rates of mucosal
      abnormalities in a German HIV-infected cohort.
AB  - OBJECTIVES: Because of the improved life expectancy provided by successful
      antiretroviral combination therapy, preventive health measures in HIV-infected
      patients have assumed increasing importance. To date, no data exist on rates of
      mucosal abnormalities detected by screening colonoscopy in > 50-year-old HIV
      infected patients in Germany. The aim of this study was to obtain such data.
      METHODS: A screening colonoscopy was offered to 159 HIV-infected patients (age >
      50 years) who presented for HIV standard of care visits at the infectious
      diseases out-patient clinic at the university hospital in Bonn over a 1-year
      period from February 2010. Pearson's chi(2) test, Fisher's exact test and the
      Mann-Whitney U-test were used for statistical analysis. RESULTS: Fifty-one
      patients (32.1%) had undergone a screening colonoscopy in the past 10 years, and
      45 patients (28.3%) were eventually screened in the observation period. The
      median age of the 96 screened patients (86% male and 14% female) was 58 years
      [interquartile range (IQR) 54-64 years]. Overall, endoscopic abnormalities were
      found in 61% of patients. Histological examination showed tubular adenomas in
      21.9% of patients, tubulovillous adenomas in 3.1% and serrated adenomas in 1%.
      Hyperplastic polyps were found in 15.6% of patients, a nonspecific colitis in
      16.7% and diverticulosis in 12.5%. In four cases there was even an early-stage
      carcinoma (two anal, one rectal and one colon cancer). In univariate analysis, no
      significant differences with regard to immune status, highly active
      antiretroviral therapy, family history, personal risk factors or comedication
      were found between patients with dysplastic and normal mucosas. CONCLUSIONS: The
      high acceptance rate of screening colonoscopy and the in comparison with the HIV
      negative population comparably higher rate of abnormalities in this cohort of HIV
      infected patients justify enhanced implementation of screening colonoscopy in
      clinical practice.

PMID- 24127642
TI  - Generalized pustular psoriasis triggered by infliximab in two patients with
      Crohn's disease.

PMID- 24127643
TI  - Vascular endothelial growth factor receptor 1 expression in nasal polyp tissue.
AB  - BACKGROUND: Edema represents a key feature of nasal polyp (NP) disease. Members
      of the vascular endothelial growth factor (VEGF) family may be involved, but the
      precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their
      receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive. OBJECTIVE:
      Exploring the expression of VEGF family members and their receptors and their
      correlation with clinical, radiological, and edema markers in NP. METHODS: The
      expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n =
      23) and control tissue (n = 22) at mRNA and protein level. Edema was evaluated by
      measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were
      scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined
      by real-time RT-PCR. Cell suspensions from NP (n = 10) and control tissue (n =
      12) were stimulated in vitro with IL-1beta or TNFalpha. RESULTS: mRNA expression
      of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue.
      Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin
      content (VEGF-B: P = 0.0208; VEGFR1: P = 0.0293), CT scan scores (VEGF-B: P =
      0.0075; VEGFR1: P = 0.0068), and IL-5 mRNA (VEGF-B: P = 0.0027; VEGFR1: P =
      0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL
      1beta or TNFalpha significantly reduced the expression of VEGFR2 in control
      tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric
      oxide production in NP macrophages (P < 0.05). CONCLUSION: Expression levels of
      VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and
      therefore represent potential therapeutic targets.

PMID- 24127644
TI  - Transgenic expression of pectin methylesterase inhibitors limits tobamovirus
      spread in tobacco and Arabidopsis.
AB  - Plant infection by a virus is a complex process influenced by virus-encoded
      factors and host components which support replication and movement. Critical
      factors for a successful tobamovirus infection are the viral movement protein
      (MP) and the host pectin methylesterase (PME), an important plant counterpart
      that cooperates with MP to sustain viral spread. The activity of PME is modulated
      by endogenous protein inhibitors (pectin methylesterase inhibitors, PMEIs). PMEIs
      are targeted to the extracellular matrix and typically inhibit plant PMEs by
      forming a specific and stable stoichiometric 1:1 complex. PMEIs counteract the
      action of plant PMEs and therefore may affect plant susceptibility to virus. To
      test this hypothesis, we overexpressed genes encoding two well-characterized
      PMEIs in tobacco and Arabidopsis plants. Here, we report that, in tobacco plants
      constitutively expressing a PMEI from Actinidia chinensis (AcPMEI), systemic
      movement of Tobacco mosaic virus (TMV) is limited and viral symptoms are reduced.
      A delayed movement of Turnip vein clearing virus (TVCV) and a reduced
      susceptibility to the virus were also observed in Arabidopsis plants
      overexpressing AtPMEI-2. Our results provide evidence that PMEIs are able to
      limit tobamovirus movement and to reduce plant susceptibility to the virus. 

PMID- 24127646
TI  - Alkynyl complexes of high-valence clusters. synthesis and luminescence properties
      of [Mo6I8(C=CC(O)OMe)6]2-, the first complex with exclusively organometallic
      outer ligands in the family of octahedral {M6X8} clusters.
AB  - The reaction of [Mo6I14](2-) with methyl propiolate HC=CC(O)OMe in the presence
      of Ag(+) and Et3N yielded the new luminescent complex [Mo6I8(C=CC(O)OMe)6](2-),
      the first fully organometallic complex in the family of octahedral {M6X8}
      clusters. The cluster was crystallized as tetraphenylphosphonium salt and
      characterized by X-ray single-crystal diffraction and elemental analyses, mass
      spectrometry, (13)C NMR, UV-vis, and luminescence spectroscopies. 

PMID- 24127645
TI  - Cytology in nipple aspirate fluid during a randomized soy food intervention among
      premenopausal women.
AB  - Because soy food consumption may influence breast tissue activity, we examined
      its effect on the presence of epithelial cells in nipple aspirate fluid (NAF). In
      a randomized, crossover design, 82 premenopausal women completed a high-soy and a
      low-soy diet for 6 mo each, separated by a 1-mo washout period. They provided NAF
      samples at baseline, 6 mo, and 13 mo during the midluteal phase of the menstrual
      cycle. Papanicolaou-stained cytology slides (for 33 women at baseline, 24 at low
      soy, and 36 at high-soy) were evaluated in women with sufficient NAF. Mixed
      models evaluated the effect of the high-soy diet on epithelial cytology as
      compared to baseline and the low-soy diet. At the end of the high-soy diet,
      cytological subclass had decreased in 8 (24%) and increased in 3 (9%) women as
      compared to baseline, whereas the respective values were 3 (14%) and 6 (29%) for
      the low-soy diet samples (P = 0.32). Only the change in subclass indicated a
      trend in lower cytological class (P = 0.06). Contrary to an earlier report, the
      number of NAF samples with hyperplastic epithelial cells did not increase after a
      soy intervention in amounts consumed by Asians. 

PMID- 24127647
TI  - Risk factors for epilepsy in Nigerians - a cross-sectional case-control study.
AB  - OBJECTIVE: The identification of risk factors that predispose to development of
      epilepsy is crucial to its primary prevention. This study evaluated the risks
      conferred by some predisposing factors. PATIENTS AND METHODS: This cross
      sectional analytical study assessed the relative contributions of various risk
      factors to development of epilepsy in 244 adult Nigerians with epilepsy compared
      with equal number of age- and sex-matched controls. Odds ratio and Fisher exact
      test were used to express significant association. RESULTS: Birth asphyxia (OR
      6.87), recurrent childhood febrile convulsions (OR 5.74), central nervous system
      (CNS) infections (OR 3.38), head trauma (OR 1.82), rural dwelling without health
      care access (OR 2.44), and history of epilepsy in first-degree relatives (OR
      3.44) were identified as significant risk factors for epilepsy. CONCLUSIONS:
      Prompt diagnosis and appropriate treatment for febrile diseases and CNS
      infections, use of head helmets and car seat belts would contribute to reduced
      incidence.

PMID- 24127648
TI  - The clinical significance of drug-drug interactions in the era of direct-acting
      anti-viral agents against chronic hepatitis C.
AB  - BACKGROUND: Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C
      infection became a potential challenge with the introduction of direct-acting
      anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs)
      telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P
      glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.
      AIM: To analyse the risk for DDIs in patients with chronic HCV genotype 1
      infection considered for PI treatment at a tertiary referral centre. METHODS: The
      first 115 consecutive patients selected for a PI therapy at Hannover Medical
      School were included. All changes to co-medication before and during PI treatment
      were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites
      and the respective prescribing information. RESULTS: Out-patient medication
      contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11).
      The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients.
      Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs
      newly prescribed during anti-viral therapy were considerable in 42% of the
      patients. Suspected DDIs were managed by dose adjustments and discontinuation of
      co-medication in 7% and 21% of the patients respectively. CONCLUSIONS: Many
      patients with chronic HCV genotype 1 infection are affected by potential DDIs if
      treated with a protease inhibitor, but only in a minority of cases co-medication
      is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but
      well manageable by a careful review of the patient's drug chart and monitoring
      during treatment.

PMID- 24127649
TI  - Donor pre-treatment in clinical kidney transplantation: a critical appraisal.
AB  - Kidney transplantation represents one of the medical achievements of the 20th
      century. However, its continued success is limited by the increasing shortage of
      donor grafts. As a result, more kidney grafts from marginal donors are being
      considered for transplantation, with concomitantly more initial graft injury and
      limited organ and patient survival. This has led to an increased need for
      interventions aiming to optimize and preserve graft quality. Interventions within
      the donor may protect against ischemia/reperfusion injury, and therefore, donor
      pre-treatment is a promising strategy to increase graft function and survival.
      During the last decade, diverse donor pre-treatment interventions have been
      explored in animal studies. Moreover, the first human trials concerning donor pre
      treatment in kidney transplantation have provided encouraging results.
      Unfortunately, it remains difficult to determine how and where to intervene in
      the multifactorial and complex processes that affect the donor kidney. Moreover,
      ethical matters play a critical role in donor interventions, and pre-treatment
      should principally not have any potentially unfavorable effects on other organs
      to be transplanted or on the living donor. This review provides an overview of
      promising therapeutical strategies for donor pre-treatment in kidney
      transplantation and discusses the clinical trials that have been conducted thus
      far. 

PMID- 24127650
TI  - Context dependent memory in two learning environments: the tutorial room and the
      operating theatre.
AB  - BACKGROUND: Psychologists have previously demonstrated that information recall is
      context dependent. However, how this influences the way we deliver medical
      education is unclear. This study aimed to determine if changing the recall
      context from the learning context affects the ability of medical students to
      recall information. METHODS: Using a free recall experimental model, fourteen
      medical student participants were administered audio lists of 30 words in two
      separate learning environments, a tutorial room and an operating theatre. They
      were then asked to recall the words in both environments. While in the operating
      theatre participants wore appropriate surgical clothing and assembled around an
      operating table. While in the tutorial room, participants dressed casually and
      were seated around a table. Students experienced the same duration (15 minutes)
      and disruption in both environments. RESULTS: The mean recall score from the 28
      tests performed in the same environment was 12.96 +/- 3.93 (mean, SD). The mean
      recall score from the 28 tests performed in an alternative environment to the
      learning episode was 13.5 +/- 5.31(mean, SD), indicating that changing the recall
      environment from the learning environment does not cause any statistical
      difference (p=0.58). The average recall score of participants who learned and
      recalled in the tutorial room was 13.0 +/- 3.84 (mean, SD). The average recall
      score of participants who learnt and recalled in the operating theatre was 12.92
      +/- 4.18 (mean, SD), representing no significant difference between the two
      environments for learning (p=0.4792). CONCLUSIONS: The results support the
      continued use of tutorial rooms and operating theatres as appropriate
      environments in which to teach medical students, with no significant difference
      in information recall seen either due to a same context effect or specific
      context effect.

PMID- 24127652
TI  - The crystal structure of Pseudomonas putida azoreductase - the active site
      revisited.
AB  - The enzymatic degradation of azo dyes begins with the reduction of the azo bond.
      In this article, we report the crystal structures of the native azoreductase from
      Pseudomonas putida MET94 (PpAzoR) (1.60 A), of PpAzoR in complex with
      anthraquinone-2-sulfonate (1.50 A), and of PpAzoR in complex with Reactive Black
      5 dye (1.90 A). These structures reveal the residues and subtle changes that
      accompany substrate binding and release. Such changes highlight the fine control
      of access to the catalytic site that is required by the ping-pong mechanism, and
      in turn the specificity offered by the enzyme towards different substrates. The
      topology surrounding the active site shows novel features of substrate
      recognition and binding that help to explain and differentiate the substrate
      specificity observed among different bacterial azoreductases. 

PMID- 24127651
TI  - Lower mortality following pulmonary adverse events and sepsis with ticagrelor
      compared to clopidogrel in the PLATO study.
AB  - In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with
      acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel
      but the mechanisms for this mortality reduction remain uncertain. We analysed
      adverse events (AEs) consistent with either pulmonary infection or sepsis, and
      subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or
      clopidogrel. AEs occurring within 7 days of last dose of study medication were
      defined as "on-treatment". Serial measurements of blood leukocyte counts, C
      reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary
      AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331
      respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p <
      0.001), particularly in those who remained on study medication three days after
      AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in
      the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the
      clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1
      month post-discontinuation. C-reactive protein increased more at discharge in the
      ticagrelor group (28.0 +/- 38.0 vs. 26.1 +/- 36.6 mg/l; p < 0.001) and
      interleukin-6 remained higher during the first month of treatment with
      ticagrelor. We conclude that the mortality risk following pulmonary AEs and
      sepsis in acute coronary syndrome patients appears to be lower during ticagrelor
      compared to clopidogrel therapy. Further work should assess whether ticagrelor
      and clopidogrel have differential effects on immune signalling.

PMID- 24127653
TI  - Quantification of microbial risks to human health caused by waterborne viruses
      and bacteria in an urban slum.
AB  - AIMS: To determine the magnitude of microbial risks from waterborne viruses and
      bacteria in Bwaise III in Kampala (Uganda), a typical slum in Sub-Saharan Africa.
      METHODS AND RESULTS: A quantitative microbial risk assessment (QMRA) was carried
      out to determine the magnitude of microbial risks from waterborne pathogens
      through various exposure pathways in Bwaise III in Kampala (Uganda). This was
      based on the concentration of Escherichia coli O157:H7, Salmonella spp.,
      rotavirus (RV) and human adenoviruses F and G (HAdV) in spring water, tap water,
      surface water, grey water and contaminated soil samples. The total disease burden
      was 680 disability-adjusted life years (DALYs) per 1000 persons per year. The
      highest disease burden contribution was caused by exposure to surface water open
      drainage channels (39%) followed by exposure to grey water in tertiary drains
      (24%), storage containers (22%), unprotected springs (8%), contaminated soil (7%)
      and tap water (0.02%). The highest percentage of the mean estimated infections
      was caused by E. coli O157:H7 (41%) followed by HAdV (32%), RV (20%) and
      Salmonella spp. (7%). In addition, the highest infection risk was 1 caused by
      HAdV in surface water at the slum outlet, while the lowest infection risk was
      2.71 * 10(-6) caused by E. coli O157:H7 in tap water. CONCLUSIONS: The results
      show that the slum environment is polluted, and the disease burden from each of
      the exposure routes in Bwaise III slum, with the exception of tap water, was much
      higher than the WHO reference level of tolerable risk of 1 * 10(-6) DALYs per
      person per year. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study
      provide guidance to governments, local authorities and nongovernment
      organizations in making decisions on measures to reduce infection risk and the
      disease burden by 10(2) to 10(5) depending on the source of exposure to achieve
      the desired health impacts. The infection risk may be reduced by sustainable
      management of human excreta and grey water, coupled with risk communication
      during hygiene awareness campaigns at household and community level. The data
      also provide a basis to make strategic investments to improve sanitary conditions
      in urban slums.

PMID- 24127654
TI  - Are statins 'IDEAL' for non-alcoholic fatty liver disease?
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease and cause of elevated serum liver enzyme activities in the developed
      world. Obesity, diabetes mellitus (DM), and dyslipidaemia, common components of
      the metabolic syndrome (MetS), are frequently associated with NAFLD; 75-100% of
      patients with MetS or DM have NAFLD. NAFLD is characterized by hepatic
      triglyceride (TG) infiltration in the absence of alcohol abuse or chronic liver
      disease. NAFLD includes a spectrum of conditions varying from steatosis to
      steatosis with inflammation [steatohepatitis (NASH)], necrosis, fibrosis or
      cirrhosis that rarely progresses to hepatocellular carcinoma. NAFLD and NASH are
      the hepatic manifestations of MetS and are associated with increased
      cardiovascular disease (CVD) risk. Most NAFLD/NASH patients die from CVD rather
      than from liver disease. There is no universally accepted treatment for NAFLD.

PMID- 24127655
TI  - Epigallocatechin-3-gallate inhibits hepatoblastoma growth by reactivating the Wnt
      inhibitor SFRP1.
AB  - Activation of Wnt signaling plays a central role in the formation of
      hepatoblastoma (HB), the most common pediatric liver cancer. Blocking this
      pathway with specific inhibitors is currently the target of various research
      endeavours. This study provides evidence that the naturally occurring flavonoid
      epigallocatechin-3-gallate (EGCG) is highly effective against HB growth through
      inhibition of Wnt signaling. We demonstrate that EGCG has a strong cytotoxic
      effect on HB cells in a time- and dose-dependent manner by impinging on cell
      viability, while leaving normal fibroblasts unaffected. Apoptotic features,
      including morphological changes, caspase 3 activity, and proteolytic cleavage of
      poly(ADP-ribose) polymerase, were frequently found in EGCG-treated HB cells,
      thereby suggesting involvement of the mitochondrial intrinsic apoptotic pathway.
      We furthermore show that EGCG effectively inhibits Wnt signaling, as evidenced by
      down-regulation of Wnt-responsive reporter gene activity and expression of the
      Wnt target genes MYC and CCND1. Interestingly, EGCG induced reexpression of the
      tumor suppressor gene SFRP1, which is transcriptionally silenced in HB cells and
      known to down-regulate Wnt signaling. Considering the lack of toxic effects on
      normal cells, EGCG should be preclinically validated as an adjuvant therapy in
      vivo with the ultimate goal of determining its efficacy in human trials. 

PMID- 24127657
TI  - Learning and personality types are related in cavies (Cavia aperea).
AB  - The evolution and maintenance of consistent individual differences, so called
      animal personalities, have attracted much research interest over the past
      decades. Variation along common personality traits, such as boldness or
      exploration, is often associated with risk-reward trade-offs. Individuals that
      are bolder and hence take more risks may be more successful in acquiring
      resources over the short term. Cautious individuals taking fewer risks may, on
      the other hand, live longer, but may also gather fewer resources over the short
      term. According to recent theory, individual differences in personality may be
      functionally related to individual differences in cognitive performance (i.e.,
      the way in which individuals acquire or use information). Individual differences
      in the acquisition speed of cognitively challenging tasks are often associated
      with a speed-accuracy trade-off. Accuracy can be improved by investing more time
      in the decision-making process or, conversely, decisions can be made more quickly
      at the cost of making more mistakes. Hence, the speed-accuracy trade-off often
      involves a risk-reward trade-off. We tested whether 3 personality traits,
      boldness, activity, and aggressiveness, are correlated with individual learning,
      associative learning speed, and behavioral flexibility as assessed by reversal
      learning in wild cavies (Cavia aperea). We found strong positive relationships
      between all personality traits and learning speed, whereas flexibility was
      negatively associated with aggressiveness. Our results support the hypothesis
      that performance reflects individual differences in personality in a predictable
      way.

PMID- 24127658
TI  - Quantification of fluoride in food by microwave acid digestion and fluoride ion
      selective electrode.
AB  - To quantify fluoride in food it is necessary to extract the fluoride from the
      matrix. Dry ashing (alkali fusion) and facilitated diffusion are the methods most
      commonly used, but their application requires lengthy treatments. The present
      study proposes the use of a microwave oven and 7 mol/L nitric acid for simple,
      rapid digestion of foods for fluoride analysis. The analyte is subsequently
      quantified by fluoride ion-selective electrode. The various steps of the method
      were optimized and an in-house validation was performed. The limit of
      quantification (0.130 mg/kg), trueness (92%), recovery (84-101%), and precision
      (1-8%) were determined. These analytical characteristics are satisfactory and
      show the suitability of the method for analysis of fluoride in foods of various
      kinds. The method's ease of application and the use of equipment normally found
      in food analysis laboratories may help to further increase research on fluoride
      concentrations in foods consumed by the population. 

PMID- 24127659
TI  - Exploitation of long-lived 3IL excited states for metal-organic photodynamic
      therapy: verification in a metastatic melanoma model.
AB  - Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized,
      characterized according to their photophysical and photobiological properties,
      and evaluated for their collective potential as photosensitizers for metal
      organic photodynamic therapy. The dyads in this series possess lowest-lying (3)IL
      based excited states with lifetimes that can be tuned from 22 to 270 MUs in fluid
      solution and from 44 to 3440 MUs in glass at 77 K. To our knowledge, these
      excited-state lifetimes are the longest reported for Ru(II)-based dyads
      containing only one organic chromophore and lacking terminal diimine groups.
      These excited states proved to be extremely sensitive to trace amounts of oxygen,
      owing to their long lifetimes and very low radiative rates. Herein, we
      demonstrate that (3)IL states of this nature are potent photodynamic agents,
      exhibiting the largest photocytotoxicity indices reported to date with nanomolar
      light cytotoxicities at very short drug-to-light intervals. Importantly, these
      new agents are robust enough to maintain submicromolar PDT in pigmented
      metastatic melanoma cells, where the presence of melanin in combination with low
      oxygen tension is known to compromise PDT. This activity underscores the
      potential of metal-organic PDT as an alternate treatment strategy for challenging
      environments such as malignant melanoma. 

PMID- 24127660
TI  - High-content pSTAT3/1 imaging assays to screen for selective inhibitors of STAT3
      pathway activation in head and neck cancer cell lines.
AB  - The oncogenic transcription factor signal transducer and activator of
      transcription 3 (STAT3) is hyperactivated in most cancers and represents a
      plausible therapeutic target. In the absence of STAT3-selective small-molecule
      inhibitors, we sought to develop pSTAT3/1 high-content imaging (HCS) assays to
      screen for selective inhibitors of STAT3 pathway activation in head and neck
      squamous cell carcinomas (HNSCC) tumor cell lines. Based on the expression of the
      interleukin-6 (IL-6)Ralpha and gp130 subunits of the IL-6 receptor complex and
      STAT3, we selected the Cal33 HNSCC cell line as our model. After developing image
      acquisition and analysis procedures, we rigorously investigated the cytokine
      activation responses to optimize the dynamic ranges of both assays and
      demonstrated that the pan-Janus kinase inhibitor pyridone 6 nonselectively
      inhibited pSTAT3 and pSTAT1 activation with 50% inhibition concentrations of 7.19
      +/- 4.08 and 16.38 +/- 8.45 nM, respectively. The optimized pSTAT3 HCS assay
      performed very well in a pilot screen of 1,726 compounds from the Library of
      Pharmacologically Active Compounds and the National Institutes of Health clinical
      collection sets, and we identified 51 inhibitors of IL-6-induced pSTAT3
      activation. However, only three of the primary HCS actives selectively inhibited
      STAT3 compared with STAT1. Our follow-up studies indicated that the nonselective
      inhibition of cytokine induced pSTAT3 and pSTAT1 activation by G-alpha
      stimulatory subunit-coupled G-protein-coupled receptor agonists, and forskolin
      was likely due to cyclic adenosine monophosphate-mediated up-regulation of
      suppressors of cytokine signaling 3. Azelastine, an H1 receptor antagonist
      approved for the treatment of seasonal allergic rhinitis, nonallergic vasomotor
      rhinitis, and ocular conjunctivitis, was subsequently confirmed as a selective
      inhibitor of IL-6-induced pSTAT3 activation that also reduced the growth of HNSCC
      cell lines. These data illustrate the power of a chemical biology approach to
      lead generation that utilizes fully developed and optimized HCS assays as
      phenotypic screens to interrogate specific signaling pathways.

PMID- 24127662
TI  - Diagnosis and treatment of schistosomiasis in children in the era of intensified
      control.
AB  - In the current era of intensified and integrated control against schistosomiasis
      and other neglected tropical diseases, there is a need to carefully rethink and
      take into consideration disease-specific issues pertaining to the diagnosis,
      prevention, control and local elimination. Here, we present a comprehensive
      overview about schistosomiasis including recent trends in the number of people
      treated with praziquantel and the latest developments in diagnosis and control.
      Particular emphasis is placed on children. Identified research needs are offered
      for consideration; namely, expanding our knowledge about schistosomiasis in
      preschool-aged children, assessing and quantifying the impact of schistosomiasis
      on infectious and noncommunicable diseases, developing new antischistosomal drugs
      and child-friendly formulations, designing and implementing setting-specific
      control packages and developing highly sensitive, but simple diagnostic tools
      that are able to detect very light infections in young children and in people
      living in areas targeted for schistosomiasis elimination. 

PMID- 24127661
TI  - Development of a high-throughput screening cancer cell-based luciferase refolding
      assay for identifying Hsp90 inhibitors.
AB  - The 90 kDa heat-shock protein (Hsp90) and other cochaperones allow for proper
      folding of nascent or misfolded polypeptides. Cancer cells exploit these
      chaperones by maintaining the stability of mutated and misfolded oncoproteins and
      allowing them to evade proteosomal degradation. Inhibiting Hsp90 is an attractive
      strategy for cancer therapy, as the concomitant degradation of multiple
      oncoproteins may lead to effective anti-neoplastic agents. Unfortunately, early
      clinical trials have been disappointing with N-terminal Hsp90 inhibitors, as it
      is unclear whether the problems that plague current Hsp90 inhibitors in clinical
      trials are related to on-target or off-target activity. One approach to overcome
      these pitfalls is to identify structurally diverse scaffolds that improve Hsp90
      inhibitory activity in the cancer cell milieu. Utilizing a panel of cancer cell
      lines that express luciferase, we have designed an in-cell Hsp90-dependent
      luciferase refolding assay. The assay was optimized using previously identified
      Hsp90 inhibitors and experimental novobiocin analogues against prostate, colon,
      and lung cancer cell lines. This assay exhibits good interplate precision (% CV),
      a signal-to-noise ratio (S/N) of >=7, and an approximate Z-factor ranging from
      0.5 to 0.7. Novobiocin analogues that revealed activity in this assay were
      examined via western blot experiments for client protein degradation, a hallmark
      of Hsp90 inhibition. Subsequently, a pilot screen was conducted using the
      Prestwick library, and two compounds, biperiden and ethoxyquin, revealed
      significant activity. Here, we report the development of an in-cell Hsp90
      dependent luciferase refolding assay that is amenable across cancer cell lines
      for the screening of inhibitors in their specific milieu.

PMID- 24127663
TI  - pH- and solute-dependent adsorption of single-wall carbon nanotubes onto
      hydrogels: mechanistic insights into the metal/semiconductor separation.
AB  - The gel separation of single-wall carbon nanotubes (SWCNTs) suspended in sodium
      dodecyl sulfate (SDS) is expected to be one of the most successful methods of
      large-scale and high-purity separation. Understanding the mechanism of the gel
      separation helps improve the quality and quantity of separation and reveals the
      colloidal behaviors of SWCNTs, which reflects their band structures. In this
      study, we characterize the pH- and solute-dependent adsorption of SWCNTs onto
      agarose and Sephacryl hydrogels and provide a mechanistic model of the
      metal/semiconductor separation. The adsorbability of SWCNTs is substantially
      reduced under acidic pH conditions. Importantly, the pH dependence differs
      between metallic and semiconducting species; therefore, the adsorbability is
      related to the band-structure-dependent oxidation of the SWCNTs. Oxidation
      confers positive charges on SWCNTs, and these charges enhance the electrostatic
      interactions of the SWCNTs with SDS, thereby leading to the condensation of SDS
      on the SWCNTs. This increase in SDS density reduces the interactions between the
      SWCNTs and hydrogels. Under highly basic conditions, such as pH ~12.5, or in the
      presence of salts, the adsorption is dissociative because of the condensation of
      SDS on the SWCNTs through electrostatic screening by counterions. Desorption of
      the SWCNTs from the hydrogels due to the addition of urea implies a hydrophobic
      interface between SDS-dispersed SWCNTs and the hydrogels. These results suggest
      that the metal/semiconductor separation can be explained by the alteration of the
      interaction between SDS-dispersed SWCNTs and the hydrogels through changes in the
      conformation of SDS on the SWCNTs depending on the SWCNTs' band structures. 

PMID- 24127664
TI  - Ultrafast two-dimensional infrared spectroscopy of guanine-cytosine base pairs in
      DNA oligomers.
AB  - NH and OH stretching excitations of hydrated double-stranded DNA oligomers
      containing guanine-cytosine (GC) base pairs in a Watson-Crick geometry are
      studied by two-dimensional (2D) infrared spectroscopy. The 2D spectra measured at
      a low hydration level (~4 water molecules/base pair) are dominated by NH stretch
      contributions from the NH2 groups of G and C and the NH group of G. Partially
      hydrated NH2 groups display red-shifted NH stretch frequencies and a mixing of
      the wave functions of the two local NH oscillators via the mechanical vibrational
      coupling. The NH stretch lifetimes are of the order of 200-300 fs. Weak couplings
      exist between NH stretch oscillators within a base pair, while interactions
      between neighboring GC pairs in the double helix are negligible. The absence of
      spectral diffusion on a 1 ps time scale suggests a relatively rigid structure of
      the hydrogen bonds between DNA and residual water molecules. 2D spectra recorded
      with fully hydrated DNA oligomers exhibit NH and OH stretch contributions with a
      weak influence of water fluctuations on the NH stretch lineshapes. The
      femtosecond spectral diffusion of OH stretch excitations is slower than that in
      bulk H2O and originates from structural fluctuations of the water shell and the
      formation of a vibrationally hot ground state by vibrational relaxation. We
      compare our findings with measurements on hydrated adenine-thymine DNA oligomers
      and anhydrous GC base pairs in solution. 

PMID- 24127665
TI  - Stimuli-responsive poly(caprolactone) vesicles for dual drug delivery under the
      gastrointestinal tract.
AB  - We report the first example of carboxylic functionalized poly(caprolactone) (PCL)
      block copolymer vesicles as a novel dual drug delivery pH responsive vehicle for
      oral administration under the gastrointestinal (GI) tract. A new carboxylic
      functionalized caprolactone monomer was custom designed through multistep organic
      reactions and polymerized under controlled ROP using polyethylene glycol (PEG
      2000) to produce amphiphilic diblocks, PEG-b-CPCLx, with x = 25, 50, 75, and 100.
      These carboxylic PCL block copolymers were self-organized into 100-250 nm
      vesicular assemblies in water. The size and shape of the vesicular assemblies
      were confirmed by light scattering, zeta potential, and electron microscopes.
      These vesicles were capable of loading both hydrophilic molecules (Rhodamine B,
      Rh-B) and hydrophobic drugs such as ibuprofen (IBU) and camptothecin (CPT) in the
      core and layer, respectively. These pH-responsive PCL vesicles were stable in
      strong acidic conditions (pH < 2.0, stomach) and ruptured to release the loaded
      cargoes under neutral or basic pH (7.0 <= pH, similar to that of small
      intestine). The drug release kinetics under simulated GI tract revealed that the
      individual drug loaded vesicles followed the combination of diffusion and erosion
      pathway, whereas the dual drug loaded vesicles predominantly followed the
      diffusion controlled process. Thus, the custom designed PCL vesicles open up new
      area of pH stimuli responsive polymer vehicles for delivering multiple drugs in
      oral drug delivery which are yet to be explored for biomedical applications.

PMID- 24127666
TI  - Idiopathic eruptive macular pigmentation following a Christmas tree pattern.

PMID- 24127667
TI  - Effect of prolonged general anesthesia with sevoflurane and laparoscopic surgery
      on gastric and small bowel propulsive motility and pH in dogs.
AB  - OBJECTIVE: To determine if general anesthesia with sevoflurane and laparoscopic
      surgery changed gastric and small bowel propulsive motility or pH in dogs. STUDY
      DESIGN: Prospective, controlled trial. ANIMALS: Twelve, 19-24 months old, female,
      Treeing Walker Hound dogs, weighing 23-30 kg. METHODS: Dogs were anesthetized for
      a median of 8.5 hours during another study to determine the minimum alveolar
      concentration of sevoflurane using a visceral stimulus. Gastric and small bowel
      motility were determined using a sensor capsule that measures pressure, pH and
      temperature. Gastric transit time and motility index were calculated. For 8/12
      dogs, gastric motility, pH and transit time were measured. In 4/12 dogs, small
      bowel motility and pH were measured. RESULTS: Anesthesia decreased gastric and
      small bowel motility but did not change luminal pH. Mean gastric contraction
      force decreased from median (range) 11 (8-20) to 3 (1-10) mmHg (p < 0.01) and
      gastric motility index decreased from 0.63 (0-1.58) to 0 (0-0.31; p = 0.01).
      Frequency of contractions did not change, 3.7 (1.6-4.4) versus 2.8 (0.1-5.1)
      contractions minute(-1) (p = 0.1). Gastric motility returned to normal 12-15
      hours following anesthesia. Gastric emptying was prolonged from 12 (5.3-16) to 49
      (9.75-56.25) hours (p < 0.01). Mean small bowel contraction force decreased from
      34 (24-37) to 3 (0.9-17) mmHg (p < 0.02) and motility index decreased from 3.75
      (1-4.56) to 0 (0-1.53; p = 0.02). Frequency of contractions did not change, 0.5
      (0.3-1.4) versus 1.4 (0.3-4.6) contractions minute(-1) (p = 0.11). Small bowel
      motility returned within 2 hours after anesthesia. Laparoscopy did not result in
      changes to gastric or small bowel parameters beyond those produced by general
      anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: The force of gastric and small
      bowel contractions decreased during sevoflurane anesthesia for laparoscopy.
      Although gastric motility returned to normal within 12-15 hours the impairment of
      gastric emptying lasted 30-40 hours, predisposing dogs to postoperative ileus.

PMID- 24127668
TI  - Positive impact of chronic graft-versus-host disease on the outcome of patients
      with de novo myelodysplastic syndrome after allogeneic hematopoietic cell
      transplantation: a single-center analysis of 115 patients.
AB  - To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors
      for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic
      cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with
      MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo
      HCT at our center. Eighty one patients received reduced-intensity conditioning
      (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although
      the RIC group was significantly older and included more patients with poor
      cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between
      the two groups. In a multivariate analysis, covariates associated with a worse OS
      were the French-American-British stage of refractory anemia excess blasts in
      transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20%
      or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark
      analyses, we found that the presence of cGVHD significantly improved OS in high
      risk patients or the RIC group. However, there was no difference in OS between
      those with and without cGVHD among low-risk MDS patients. These findings suggest
      that the graft-versus-leukemia effect may be more beneficial in high-risk
      patients who do not receive intensive preparative regimens. 

PMID- 24127670
TI  - Jim Peters--sportsman, soldier, surgeon.
AB  - Jim Peters, a country boy who excelled academically and in the sporting arena was
      a Victorian urological pioneer. His passion for teaching and belief in the
      development of Australasian urology resulted in the establishment of two of
      Melbourne's earliest Urology Units (which are now major academic University
      departments), the creation of a formal urological training program and the
      promotion of Australian urology within the International urological community. 

PMID- 24127671
TI  - The role of magnetic resonance imaging in the diagnosis and management of
      prostate cancer.
AB  - BACKGROUND: The diagnosis of prostate cancer has long been plagued by the absence
      of an imaging tool that reliably detects and localises significant tumours.
      Recent evidence suggests that multi-parametric MRI could improve the accuracy of
      diagnostic assessment in prostate cancer. This review serves as a background to a
      recent USANZ position statement. It aims to provide an overview of MRI techniques
      and to critically review the published literature on the clinical application of
      MRI in prostate cancer. TECHNICAL ASPECTS: The combination of anatomical (T2
      weighted) MRI with at least two of the three functional MRI parameters - which
      include diffusion-weighted imaging, dynamic contrast-enhanced imaging and
      spectroscopy - will detect greater than 90% of significant (moderate to high
      risk) tumours; however MRI is less reliable at detecting tumours that are small
      (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher
      anatomical resolution provided by 3-Tesla magnets and endorectal coils may
      improve the accuracy, particularly in primary tumour staging. SCREENING: The use
      of mpMRI to determine which men with an elevated PSA should undergo biopsy is
      currently the subject of two large clinical trials in Australia. MRI should be
      used with caution in this setting and then only in centres with established uro
      radiological expertise and quality control mechanisms in place. There is
      sufficient evidence to justify using MRI to determine the need for repeat biopsy
      and to guide areas in which to focus repeat biopsy. IMAGE-DIRECTED BIOPSY: MRI
      directed biopsy is an exciting concept supported by promising early results, but
      none of the three proposed techniques have so far been proven superior to
      standard biopsy protocols. Further evidence of superior accuracy and core
      efficiency over standard biopsy is required, before their costs and complexities
      in use can be justified. TREATMENT SELECTION AND PLANNING: When used for primary
      tumour staging (T-staging), MRI has limited sensitivity for T3 disease, but its
      specificity of greater than 95% may be useful in men with intermediate-high risk
      disease to identify those with advanced T3 disease not suitable for nerve sparing
      or for surgery at all. MRI appears to be of value in planning dosimetry in men
      undergoing radiotherapy, and in guiding selection for and monitoring on active
      surveillance.

PMID- 24127672
TI  - Penile cancer and phallus preservation strategies: a review of current
      literature.
AB  - Penile cancer is a rare malignancy in most developed nations but its management
      can have significant anatomical, functional and psychological effects in
      patients. Whilst total penectomy used to be widely practiced, it is associated
      with significant psychological consequences pertaining to body image and
      masculinity, with loss of sexual function and the ability to void upright. Recent
      advances in surgical techniques and technologies has allowed for many organ
      sparing techniques with acceptable psychosexual and oncological outcomes. Factors
      to be considered in phallus preservation treatment include: local invasion,
      tumour stage and the ability to achieve complete oncological control. Topical
      chemotherapeutic agents, laser ablation, radiotherapy, Mohs micrographic surgery,
      glansectomy and partial penectomy have been frequently used to interfere as
      little as possible with functional anatomy without compromising local cancer
      control. The difficulty with these phallus-preserving techniques is the potential
      risk of disease recurrence both locally and distally. Providing that patients are
      suitable for penile-sparing therapy, have been informed adequately on risk of
      tumour recurrence and are willing to commit to rigorous close surveillance, good
      functional outcome as well as oncological control can be achieved. 

PMID- 24127673
TI  - Metaplastic conditions of the bladder.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD? Urologists are often
      confronted with cystoscopic appearances that at times are abnormal but non
      specific, may mimic urothelial carcinoma or in some instances are quite bizarre
      given the clinical scenarios in which they occur (e.g. changes associated with a
      catheter will be more obvious than a de-novo presentation of cystitis cystica).
      Metaplasias of the bladder urothelium make up the majority of such cases.
      Furthermore, when confronted with a pathological diagnosis of a metaplasia within
      the bladder- what are the implications for the patient and how should they be
      followed-up? This review provides a concise summary of the pathological features
      of the various metaplasias that occur in the bladder and briefly describes their
      current treatment and requirement for follow-up. Metaplasia of the bladder
      urothelium occurs commonly in response to local injury. Usually the changes are
      reversible, but some conditions may be premalignant. This review describes the
      different metaplastic entities and their clinical significance. Most importantly,
      keratinising squamous metaplasia is a precursor to the development of bladder
      cancer, and requires treatment and long term follow up. The role of intestinal
      metaplasia in the development of cancer is uncertain, and these patients require
      follow-up until further evidence is obtained on the outcome of this entity.

PMID- 24127674
TI  - Diagnostic challenges in the evaluation of persistent or recurrent urinary
      incontinence after artificial urinary sphincter (AUS) implantation in patients
      after prostatectomy.
AB  - There is a lack of information pertaining to the postoperative evaluation in
      patients with artificial urinary sphincter (AUS) implants who complain and
      continue to have urinary incontinence (UI). Two types of UI can occur after the
      activation of an AUS device these are: early or initial (persistent) UI, and
      delayed (recurrent) UI. There are many causes of persistent and/or recurrent UI
      and these can sometimes overlap. The potential causes include improper and/or
      accidental operation of the pump-control unit, overactive bladder, cuff atrophy,
      cuff erosion, improper cuff size and pressure-regulating balloon unit, as well as
      device malfunctions. The diagnostic evaluation in men with persistent and/or
      recurrent UI after AUS implantation requires sufficient understanding of the AUS
      mechanics and is a step-wise and logical process with careful history and
      thorough clinical evaluation. Once a diagnosis is made, patients should be
      counselled and appropriate treatment instituted. 

PMID- 24127675
TI  - Contemporary management of renal cell carcinoma (RCC) in Victoria: implications
      for longer term outcomes and costs.
AB  - OBJECTIVE: To describe the contemporary patterns of care for renal cell carcinoma
      (RCC) using a whole of population series from Victoria. PATIENTS AND METHODS:
      Retrospective review of medical records of all patients diagnosed and treated for
      RCC in Victoria in 2009. Patients were identified via the State-wide Victorian
      Cancer Registry. Patient demographic characteristics, symptoms, stage, and first
      line treatment were assessed. Associations between case residential location
      (metropolitan or rural) and treatment were examined using multivariate logistic
      regression after adjusting for age, sex, socioeconomic status, treatment in
      private or public hospital and comorbidity. RESULTS: Data were obtained for 499
      of 577 eligible patients. In all, 413 patients (83%) underwent surgery.
      Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I
      pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of
      Stage I RCC In multivariate analysis, regional patients were less likely to
      receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18-0.85) for
      Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR
      0.06, 95% CI 0.01-0.41). Multidisciplinary team meetings were recorded for only
      25% of patients and 3% were enrolled in a clinical trial. CONCLUSION: Most
      contemporary patients diagnosed with RCC are still treated with RN, including
      those with smaller tumours amenable to PN. This may impact future outcomes,
      including increased risk of chronic kidney disease and its potential financial
      healthcare burden. Patterns of treatment also appear to differ between
      metropolitan and regional populations.

PMID- 24127676
TI  - Editorial comment on 'Contemporary management of renal cell carcinoma in
      Victoria: implications for longer term outcomes and costs'.

PMID- 24127677
TI  - Non-invasive urodynamics predicts outcome prior to surgery for prostatic
      obstruction.
AB  - OBJECTIVE: To assess whether the penile cuff non-invasive urodynamic test serves
      as an effective diagnostic tool for predicting outcomes prior to disobstructive
      surgery for men presenting with voiding lower urinary tract symptoms. Patients
      with proven urodynamic obstruction do better after surgery. The current gold
      standard, invasive pressure-flow studies, imposes cost, resource demand,
      discomfort and inconvenience to patients. PATIENTS AND METHODS: Patients
      undergoing surgery for prostatic obstruction at Palmerston North Hospital had pre
      operative non-invasive urodynamics and completed an International Prostate
      Symptom Score (IPSS). Catheterised patients were excluded. Two months post
      operatively they completed a further IPSS score. An improvement of seven or
      greater was defined as a clinically successful outcome. Results were compared
      with the outcome predicted by the nomogram supplied with the urodynamic device.
      RESULTS: Data was obtained for 62 patients with mean age 70 years (range 49 to 86
      years; SD 9 years). Follow-up was complete for all patients. Thirty-eight
      patients underwent transurethral resection and 24 holmium laser enucleation of
      the prostate. Mean IPSS score was 21 (range 5 to 35; SD 6) pre-operatively and 11
      (range 1 to 31; SD 9) post-operatively. Thirty-five patients were predicted
      obstructed and 27 not obstructed. 94% of those predicted obstructed had a
      successful outcome (p < 0.01). 70% predicted as not obstructed did not have a
      successful outcome after surgery (p < 0.01). CONCLUSION: The penile cuff test is
      an exciting adjunct in the decision to proceed to surgery for prostatic
      obstruction. Patients predicted to be obstructed have an excellent likelihood of
      a good surgical outcome, yet 30% of those shown not to be obstructed will still
      do well. Whilst numbers in our study are small, outcomes compare favourably with
      published results on invasive urodynamic methods.

PMID- 24127678
TI  - Changes in upper urinary tract stone composition in Australia over the past 30
      years.
AB  - OBJECTIVES: To investigate upper urinary tract stone composition rates in
      Australia To investigate changes in stone composition in Australia over the past
      30 years PATIENTS AND METHODS: The Institute for Clinical Pathology and Medical
      Research (ICPMR) database was used to obtain - stone composition statistics from
      2009-2011 Historical comparisons of stone composition rates were obtained from
      previous Australian studies; Rofe; 1981, and Baker; 1993 for epidemiological data
      from the 1970s and 1980s respectively. Stone composition data was separated into
      gender and age-groups RESULTS: From the 791 stones analysed between 2009 and
      2011, calcium oxalate remains the dominant type accounting for 64% of stones in
      our dataset, which compares to 68% from both the 1970s and 1980s. Uric acid
      stones contributed 16% of contemporary stone compositions, comparable to 16% in
      the 1970s and 17% in the 1980s. Struvite stones showed a decreasing trend from
      14% in the 1970s, to 12% in the 1980s and 7% in the current data. For struvite
      stones, while the female 21-30 age-group was the most prolific for struvite stone
      formation in the 1980s, the peak group in contemporaneous records is 61-70 year
      old men. CONCLUSION: Stone composition in Australia has remained relatively
      static over the past 30 years. Modifications in diet and body habitus have not
      resulted in significant changes in the proportion of uric acid and calcium
      oxalate stones detected. The decreasing trend in the proportion of struvite
      stones most likely reflects improved management of urinary tract infections
      within the Australian population.

PMID- 24127679
TI  - A randomised single-blind comparison of the effectiveness of Tristel Fuse
      (chlorine dioxide) as an office-based fluid soak, with Cidex OPA (ortho
      phthaldehyde) using an automated endoscopic reprocessor (AER) as high-level
      disinfection for flexible cystoscopes.
AB  - OBJECTIVE: To compare the effectiveness, safety and cost of Tristel Fuse
      (chlorine dioxide) with Cidex OPA (ortho-phthaldehyde; 1,2
      benzenedicarboxaldehyde) in an automated endoscopic reprocessor (AER) for high
      level disinfection of flexible cystoscopes. PATIENTS AND METHODS: A randomised
      single-blind study comparing the high-level disinfectants Tristel Fuse as a
      simple office-based soak and Cidex OPA using an AER was performed. Participants
      were 'blinded' to the agent used for disinfection of the flexible cystoscopes.
      All patients had negative mid-stream urine at baseline, (MSU) no symptoms
      suggestive of urinary tract infection (UTI) on the day of investigation, no
      recent antibiotic use or current indwelling urinary catheter. Patients who
      underwent cystoscopic biopsy during the procedure were excluded. A urine analysis
      was done before and 3-5 days after cystoscopy and multiple equipment cultures
      were performed. The Urogenital Distress Inventory (UDI-6 + two questions from the
      'long-form'), symptom and quality-of-life scores were assessed before and after
      cystoscopy as were ease-of-use assessments and a full cost analysis. RESULTS: In
      all, 180 of 465 screened participants were randomised 1:1 and the mean age was
      72.1 years, 17% were females and 57% of procedures were performed for bladder
      tumour surveillance. The urine analysis was positive in 5.4% of patients in each
      group and 29% (Tristel) vs 20% (Cidex) of patients had urinary leukocyturia (p =
      ns) after cystoscopy. The turnover (minutes per cycle) was 7.5 (Tristel) vs 26.7
      (Cidex). The per-procedure costs were $11.67 (American dollars) for Tristel Fuse
      and $21.82 for Cidex OPA with fixed costs of $4788 for Tristel Fuse and $60,514
      for Cidex OPA. CONCLUSIONS: Tristel Fuse appears to be as effective and more cost
      effective than Cidex OPA for high-level disinfection of flexible cystoscopes.
      This has significant cost implications for the office urologist.

PMID- 24127680
TI  - USANZ: Time-trends in use and impact on outcomes of perioperative chemotherapy in
      patients treated with radical cystectomy for urothelial bladder cancer.
AB  - OBJECTIVE: To review time-trends in the use of perioperative chemotherapy and its
      impact on oncological outcomes in patients with bladder urothelial cancer (UC) at
      a single tertiary institution. PATIENTS AND METHODS: Using electronic and paper
      medical records, 89 patients were identified who underwent radical cystectomy
      with or without perioperative chemotherapy between 2004 and 2011 at Austin Health
      in Melbourne, Australia. Patient demographics, clinico-pathological
      characteristics and details of recurrence and death were assessed by
      retrospective chart review. Survival analysis was carried out using the Kaplan
      Meier method, with the impact of predictors assessed using Cox proportional
      hazard models. RESULTS: The median (range) age of this cohort was 65 (37-84)
      years, and 66 (74%) patients were male. Pathologic features included 68 (76%)
      pure UC, 21 (24%) mixed UC and 84 (94%) high grade tumours. On clinical staging,
      63 (71%) patients had muscle-invasive bladder cancer (cT-stage >= T2), of whom 11
      (17%) received neoadjuvant chemotherapy, with an increasing trend in use over
      time. Following radical cystectomy, pT-stage >= T3 and/or node positive were
      identified in 35 (39%) patients, of whom 16 (46%) received adjuvant chemotherapy.
      In addition, five patients with stage pT2 received adjuvant chemotherapy. Of the
      total cohort of patients, 31 (35%) suffered recurrences, and 33 died, 27 from
      urothelial carcinoma. On multivariate analysis, after adjusting for age, pT-stage
      and pN-stage, perioperative chemotherapy was associated with a significantly
      lower risk of recurrence [relative risk (RR) 0.41, p < 0.05], but not death from
      cancer or all causes. CONCLUSIONS: Perioperative chemotherapy, and in particular
      neoadjuvant chemotherapy, remains relatively under-utilised at our institution
      despite recent increases. The significant reduction in the risk of recurrence
      following treatment with perioperative chemotherapy with radical cystectomy
      highlights the importance of multi-modality treatment in bladder UC. Identifying
      barriers to more widespread implementation of perioperative chemotherapy is
      critical for enhancing outcomes in patients with bladder UC.

PMID- 24127681
TI  - Total synthesis, stereochemical assignment, and biological activity of all known
      (-)-trigonoliimines.
AB  - A full account of our concise and enantioselective total syntheses of all known (
      )-trigonoliimine alkaloids is described. Our retrobiosynthetic analysis of these
      natural products enabled identification of a single bistryptamine precursor as a
      precursor to all known trigonoliimines through a sequence of transformations
      involving asymmetric oxidation and reorganization. Our enantioselective syntheses
      of these alkaloids enabled the revision of the absolute stereochemistry of (-)
      trigonoliimines A, B, and C. We report that trigonoliimines A, B, C and
      structurally related compounds showed weak anticancer activities against HeLa and
      U-937 cells. 

PMID- 24127682
TI  - Pattern recognition analysis for hepatotoxicity induced by acetaminophen using
      plasma and urinary 1H NMR-based metabolomics in humans.
AB  - Drug-induced liver injury (DILI) is currently an increasingly relevant health
      issue. However, available biomarkers do not reliably detect or quantify DILI
      risk. Therefore, the purpose of this study was to comparatively evaluate plasma
      and urinary biomarkers obtained from humans treated with acetaminophen (APAP)
      using a metabolomics approach and a proton nuclear magnetic resonance (NMR)
      platform. APAP (3 g/day, two 500 mg tablets every 8 h) was administered to 20
      healthy Korean males (age, 20-29 years) for 7 days. Urine was collected daily
      before and during dosing and 6 days after the final dose. NMR spectra of these
      urine samples were analyzed using principal component analysis (PCA) and partial
      least-squares-discrimination analysis. Although the activities of aspartate
      aminotransferase and lactate dehydrogenase were significantly increased 7 days
      post-APAP treatment, serum biochemical parameters of aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase, total bilirubin, gamma-glutamyl
      transpeptidase, and lactate dehydrogenase were within normal range of hepatic
      function. However, urine and plasma (1)H NMR spectroscopy revealed different
      clustering between predosing and after APAP treatment for global metabolomic
      profiling through PCA. Urinary endogenous metabolites of trimethylamine-N-oxide,
      citrate, 3-chlorotyrosine, phenylalanine, glycine, hippurate, and glutarate as
      well as plasma endogenous metabolites such as lactate, glucose, 3
      hydroxyisovalerate, isoleucine, acetylglycine, acetone, acetate, glutamine,
      ethanol, and isobutyrate responded significantly to APAP dosing in humans.
      Urinary and plasma endogenous metabolites were more sensitive than serum
      biochemical parameters. These results might be applied to predict or screen
      potential hepatotoxicity caused by other drugs using urinary and plasma (1)H NMR
      analyses. 

PMID- 24127683
TI  - Water-soluble Co(III) complexes of substituted phenanthrolines with cell
      selective anticancer activity.
AB  - Transition metal complexes with substituted phenanthrolines as ligands represent
      potential anticancer products without the drawbacks of platinum complexes that
      are currently marketed. Here, we report the synthesis and cell selective
      anticancer activity of five new water-soluble Co(III) complexes with methyl
      substituted phenanthroline ligands. The complexes were characterized by elemental
      analysis, NMR, FAB-mass spectrometry, FTIR, electronic spectroscopy, and single
      crystal X-ray diffraction. Possible interaction of these complexes with DNA was
      assessed by a combination of circular dichroism, UV-vis spectroscopy titration,
      and ethidium bromide displacement assay, and the results indicated that DNA
      interaction is weak for these complexes. Cellular uptake and cytotoxicity of
      complexes at low concentrations were assessed by flow cytometry on PC-3 cells,
      while their effect on intracellular mitochondrial function was measured by MTS
      assay on HeLa and PC-3 cell lines. These complexes showed selective cytotoxicity
      with a significantly higher effect on intracellular mitochondrial function in PC
      3 cells than in HeLa cells. At low concentrations, complex 2 had the highest
      cytotoxic effect on PC-3 cells, inducing around 38% cell death, and the
      correlation of cytotoxicity of these complexes to their hydrophobicity indicates
      that an appropriate value of the hydrophobicity is essential for high antitumor
      activity. 

PMID- 24127684
TI  - Focal nodular hyperplasia: a review of current indications for and outcomes of
      hepatic resection.
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) is a common benign disease of the
      liver with no recognized potential for malignant transformation. The term
      describes an entity of lobular proliferation of normally differentiated
      hepatocytes, frequently around a central fibrous scar. Two key issues influence
      surgical decision making in FNH: diagnostic certainty, and symptomatic
      assessment. METHODS: A systematic review of studies reporting hepatic resections
      of FNH was performed. Indications and outcomes in adult populations were examined
      with a focus on diagnostic workup, patient selection and operative mortality and
      morbidity. RESULTS: Diagnostic modalities in the majority of studies involved
      ultrasound and computed tomography. Fewer than half employed magnetic resonance
      imaging (MRI). In instances in which MRI was not available, diagnostic accuracy
      was inferior. CONCLUSIONS: Percutaneous biopsy should be avoided to prevent the
      risk for tumour seeding. Patients presenting with asymptomatic definitive FNH can
      be safely managed conservatively. In symptomatic patients surgical resection is a
      safe and effective treatment for which acceptable rates of morbidity (14%) and
      zero mortality are reported. However, evidence of symptom resolution is reported
      with conservative strategies. Diagnostic uncertainty remains the principal valid
      indication for FNH resection, but only in patients in whom contrast-enhanced MRI
      forms part of preoperative assessment.

PMID- 24127685
TI  - Concepts of functioning and health important to children with an obstetric
      brachial plexus injury: a qualitative study using focus groups.
AB  - AIMS: The aims of this study were to explore and understand the perspectives of
      children with an obstetric brachial plexus injury (OBPI) regarding functioning
      and health, and to create an overview of problems and difficulties that patients
      encounter in daily life. METHOD: We conducted a focus group study with 48
      children (25 male, 23 female), aged 8 to 18 years, with an OBPI. Eleven open
      ended questions regarding problems or difficulties in daily life were asked in
      group sessions with 4 to 7 children within the same age range. These group
      sessions were tape-recorded and transcribed verbatim. All problems and
      difficulties mentioned in each focus group were linked to corresponding
      categories of the International Classification of Functioning, Disability and
      Health - Children & Youth Version (ICF-CY). RESULTS: Eight focus groups were
      conducted. A total of 143 unique ICF-CY categories were identified. Of these
      categories, 61 (43%) were related to the ICF-CY component 'activities and
      participation', 31 (22%) were related to 'body functions', 29 (20%) were related
      to 'environmental factors', and 22 (15%) were related to 'body structures'.
      INTERPRETATION: This study shows that children with OBPI experience difficulties
      in all areas of functioning, as well as in both environmental and personal
      factors.

PMID- 24127686
TI  - A dynamic method for the investigation of induced state metabolic capacities as a
      function of temperature.
AB  - BACKGROUND: Science-based recombinant bioprocess designs as well as the design of
      statistical experimental plans for process optimization (Design of Experiments,
      DoE) demand information on physiological bioprocess boundaries, such as the onset
      of acetate production, adaptation times, mixed feed metabolic capabilities or
      induced state maximum metabolic rates as at the desired cultivation temperature.
      Dynamic methods provide experimental alternatives to determine this information
      in a fast and efficient way. Information on maximum metabolic capabilities as a
      function of temperature is needed in case a reduced cultivation temperature is
      desirable (e.g. to avoid inclusion body formation) and an appropriate feeding
      profile is to be designed. RESULTS: Here, we present a novel dynamic method for
      the determination of the specific growth rate as a function of temperature for
      induced recombinant bacterial bioprocesses. The method is based on the control of
      the residual substrate concentration at non-limiting conditions with dynamic
      changes in cultivation temperature. The presented method was automated in respect
      to information extraction and closed loop control by means of in-line Fourier
      Transformation Infrared Spectroscopy (FTIR) residual substrate measurements and
      on-line first principle rate-based soft-sensors. Maximum induced state metabolic
      capabilities as a function of temperature were successfully extracted for a
      recombinant E. coli C41 fed-batch bioprocess without the need for sampling in a
      time frame of 20 hours. CONCLUSIONS: The presented method was concluded to allow
      the fast and automated extraction of maximum metabolic capabilities (specific
      growth rate) as a function of temperature. This complements the dynamic toolset
      necessary for science-based recombinant bacterial bioprocess design and DoE
      design.

PMID- 24127687
TI  - Early and sustained improvement with vilazodone in adult patients with major
      depressive disorder: post hoc analyses of two phase III trials.
AB  - OBJECTIVE: To retrospectively examine the timing of depressive symptom
      improvement in patients treated with vilazodone, a selective serotonin reuptake
      inhibitor (SSRI) and 5-HT1A partial agonist. RESEARCH DESIGN AND METHODS: Post
      hoc analyses were conducted on pooled data from two phase III, multicenter, 8
      week, double-blind, randomized, controlled trials (RCTs) of vilazodone 40 mg/day
      or placebo in adult patients with major depressive disorder (MDD). CLINICAL TRIAL
      REGISTRATION: Randomized controlled trial 1: ClinicalTrials.gov identifier:
      NCT00285376, http://ClinicalTrials.gov/ct2/show/NCT00285376 ; randomized
      controlled trial 2: ClinicalTrials.gov identifier: NCT00683592,
      http://ClinicalTrials.gov/ct2/show/NCT00683592. MAIN OUTCOME MEASURES: Montgomery
      Asberg Depression Rating Scale (MADRS) total score least squares (LS) mean change
      from baseline to Week 8; MADRS single items LS mean change from baseline; MADRS
      responder analyses: response = >=50% reduction in baseline score; cumulative
      response = proportion of patients at each assessment who achieved response that
      was sustained at all subsequent weeks; sustained response = >=50% reduction in
      baseline MADRS total score at last two visits; and sustained response plus MADRS
      score <=12 at the last two visits of the study. RESULTS: LS mean difference
      (LSMD) and 95% confidence interval (95% CI) for change from baseline to Week 8
      was significantly greater in favor of vilazodone versus placebo (-2.8 [-4.1 to 
      1.4]; p < 0.0001); differences between vilazodone and placebo were statistically
      significant beginning at Week 1. Early improvement in depressive symptoms was
      suggested by statistically significant separation from placebo on seven of ten
      MADRS single items as early as Week 1 or Week 2. A significantly greater
      proportion of vilazodone patients achieved response using all responder criteria,
      with early and sustained improvement consistently observed. CONCLUSIONS: Early
      and sustained improvement of depressive symptoms was retrospectively observed in
      patients treated with vilazodone; early findings may be related to overall
      treatment outcomes.

PMID- 24127688
TI  - Structure, biochemical characterization and analysis of the pleomorphism of
      carboxylesterase Cest-2923 from Lactobacillus plantarum WCFS1.
AB  - The hydrolase fold is one of the most versatile structures in the protein realm
      according to the diversity of sequences adopting such a three-dimensional
      architecture. In the present study, we clarified the crystal structure of the
      carboxylesterase Cest-2923 from the lactic acid bacterium Lactobacillus plantarum
      WCFS1 refined to 2.1 A resolution, determined its main biochemical
      characteristics and also carried out an analysis of its associative behaviour in
      solution. We found that the versatility of a canonical alpha/beta hydrolase fold,
      the basic framework of the crystal structure of Cest-2923, also extends to its
      oligomeric behaviour in solution. Thus, we discovered that Cest-2923 exhibits a
      pH-dependent pleomorphic behaviour in solution involving monomers, canonical
      dimers and tetramers. Although, at neutral pH, the system is mainly shifted to
      dimeric species, under acidic conditions, tetrameric species predominate. Despite
      these tetramers resulting from the association of canonical dimers, as is
      commonly found in many other carboxylesterases from the hormone-sensitive lipase
      family, they can be defined as 'noncanonical' because they represent a different
      association mode. We identified this same type of tetramer in the closest
      relative of Cest-2923 that has been structurally characterized: the sugar
      hydrolase YeeB from Lactococcus lactis. The observed associative behaviour is
      consistent with the different crystallographic results for Cest-2923 from
      structural genomics consortia. Finally, the presence of sulfate or acetate
      molecules (depending on the crystal form analysed) in the close vicinity of the
      nucleophile Ser116 allows us to identify interactions with the putative oxyanion
      hole and deduce the existence of hydrolytic activity within Cest-2923 crystals.

PMID- 24127689
TI  - Effect of multiple infections with white spot syndrome virus and Vibrio
      anguillarum on Pacific white shrimp Litopenaeus vannamei (L.): mortality and
      viral replication.
AB  - Multiple infections are commonly found in practical shrimp culture and may cause
      more serious consequences than infections by one pathogen only. Therefore, this
      study was conducted to evaluate the effect of multiple infections with white spot
      syndrome virus (WSSV) and Vibrio anguillarum on Pacific white shrimp Litopenaeus
      vannamei (L.), mortality, WSSV replication in vivo and host immune response. In
      the WSSV single-infection group (WSSV load, 2 * 10(2) copies MUL(-1)), mean
      cumulative mortality was 29.2%. In the V. anguillarum single-infection group,
      cumulative mortality was 12.5% when shrimp were challenged by 10(5) CFU mL(-1) of
      bacteria. In the co- and super-infection groups, 37.5% and 50% cumulative
      mortalities, respectively, were observed at a lower bacterial concentration of
      10(3) CFU mL(-1), suggesting that shrimp with multiple infections died earlier
      and more frequently than singly infected shrimp. WSSV load after injection was
      tracked over time by TaqMan quantitative PCR. WSSV load increased more rapidly in
      the multiple-infection groups than in the single-infection group. Additionally,
      mRNA expression of the genes encoding prophenoloxidase 1 and 2, which are closely
      involved in innate immunity in shrimp, was down-regulated more extensively in
      multiple-infection groups than in single-infection groups, as indicated by
      quantitative reverse-transcription PCR.

PMID- 24127690
TI  - Single-molecule electric revolving door.
AB  - This work proposes a new type of molecular machine, the single-molecule electric
      revolving door, which utilizes conductance dependence upon molecular conformation
      as well as destructive quantum interference. We perform electron transport
      simulations in the zero-bias limit using the Landauer formalism together with
      density functional theory. The simulations show that the open- and closed-door
      states, accompanied by significant conductance variation, can be operated by an
      external electric field. The large on-off conductance ratio (~10(5)) implies that
      the molecular machine can also serve as an effective switching device. The
      simultaneous control and detection of the door states can function at the
      nanosecond scale, thereby offering a new capability for molecular-scale devices.

PMID- 24127691
TI  - Rates and predictors of response to anti-viral treatment for hepatitis C virus in
      HIV/HCV co-infection in a nationwide study of 619 patients.
AB  - BACKGROUND: The effectiveness of anti-viral treatment for hepatitis C virus (HCV)
      in HIV/HCV co-infected patients in 'real world', clinical practice is unclear.
      AIMS: To determine the rates and predictors of sustained virological response
      (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and
      ribavirin in HIV/HCV co-infected patients. METHODS: We identified all HIV/HCV co
      infected patients who received anti-viral treatment with PEG-IFN and ribavirin in
      the Veterans Affairs healthcare system nationally between 2002 and 2009 (n =
      665). RESULTS: Sustained virological response was achieved in 21.6% overall,
      16.7% among patients with genotype 1 HCV (n = 491) and 44% among patients with
      genotype 2 or 3 HCV (n = 116). Among genotype 1-infected patients,
      characteristics that were negatively associated with SVR independently included
      baseline HCV viral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI
      0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)],
      baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine
      aminotransferase ratio >=1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR
      0.41 (0.2-0.9)]; characteristics positively associated with SVR included a
      starting dose of ribavirin >=1000-1200 mg/day [AOR 2.0 (1.1-3.7)] and
      erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3
      infected patients, only erythropoietin use was an independent predictor of SVR
      [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800 mg/day was not
      associated with SVR. CONCLUSIONS: Sustained virological response rates achieved
      with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical
      practice. The use of erythropoietin was the most important, modifiable factor
      associated with SVR.

PMID- 24127692
TI  - Next-generation sequencing, FISH mapping and synteny-based modeling reveal
      mechanisms of decreasing dysploidy in Cucumis.
AB  - In the large Cucurbitaceae genus Cucumis, cucumber (C. sativus) is the only
      species with 2n = 2x = 14 chromosomes. The majority of the remaining species,
      including melon (C. melo) and the sister species of cucumber, C. hystrix, have 2n
      = 2x = 24 chromosomes, implying a reduction from n = 12 to n = 7. To understand
      the underlying mechanisms, we investigated chromosome synteny among cucumber, C.
      hystrix and melon using integrated and complementary approaches. We identified 14
      inversions and a C. hystrix lineage-specific reciprocal inversion between C.
      hystrix and melon. The results reveal the location and orientation of 53 C.
      hystrix syntenic blocks on the seven cucumber chromosomes, and allow us to infer
      at least 59 chromosome rearrangement events that led to the seven cucumber
      chromosomes, including five fusions, four translocations, and 50 inversions. The
      12 inferred chromosomes (AK1-AK12) of an ancestor similar to melon and C. hystrix
      had strikingly different evolutionary fates, with cucumber chromosome C1
      apparently resulting from insertion of chromosome AK12 into the centromeric
      region of translocated AK2/AK8, cucumber chromosome C3 originating from a
      Robertsonian-like translocation between AK4 and AK6, and cucumber chromosome C5
      originating from fusion of AK9 and AK10. Chromosomes C2, C4 and C6 were the
      result of complex reshuffling of syntenic blocks from three (AK3, AK5 and AK11),
      three (AK5, AK7 and AK8) and five (AK2, AK3, AK5, AK8 and AK11) ancestral
      chromosomes, respectively, through 33 fusion, translocation and inversion events.
      Previous results (Huang, S., Li, R., Zhang, Z. et al., , Nat. Genet. 41, 1275
      1281; Li, D., Cuevas, H.E., Yang, L., Li, Y., Garcia-Mas, J., Zalapa, J., Staub,
      J.E., Luan, F., Reddy, U., He, X., Gong, Z., Weng, Y. 2011a, BMC Genomics, 12,
      396) showing that cucumber C7 stayed largely intact during the entire evolution
      of Cucumis are supported. Results from this study allow a fine-scale
      understanding of the mechanisms of dysploid chromosome reduction that has not
      been achieved previously. 

PMID- 24127693
TI  - Effects of dietary apigenin on tumor latency, incidence and multiplicity in a
      medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced
      breast cancer model.
AB  - Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly administered
      to postmenopausal women for hormone replacement therapy and has been associated
      with increased risk of breast cancer. MPA has been shown to accelerate the
      development of mammary tumors in a 7,12-dimethylbenz(a)anthracene (DMBA)-induced
      breast cancer animal model. Previously, we have shown that intraperitoneally
      administered apigenin effectively treated and prevented the progression of MPA
      accelerated breast cancer in DMBA-induced and xenograft mammary cancer models.
      Here we used the DMBA model to examine the chemopreventive effect of dietary
      apigenin against MPA-accelerated tumors with 3 different levels of apigenin
      (0.02%, 0.1%, and 0.5% w/w) incorporated into a phytoestrogen-free diet. Results
      showed that 0.1% dietary apigenin reduced MPA-dependent tumor incidence; however,
      the same dietary level increased tumor multiplicity in animals that developed
      tumors. Neither 0.02% nor 0.5% dietary apigenin reduced MPA-dependent tumor
      incidence or latency, and tumor multiplicity increased significantly in response
      to 0.5% apigenin. These results contrast with previous chemopreventive effects
      observed when apigenin was administered intraperitoneally, suggesting that route
      of administration may influence its action. Consequently, until further research
      clarifies the effect of dietary apigenin on progestin-accelerated mammary tumors,
      caution should be exercised when considering the flavonoid as a dietary
      supplement for preventing hormone-dependent breast cancer. 

PMID- 24127694
TI  - Atypical sneezing attack induced by lateral medullary infarction.

PMID- 24127695
TI  - DNA-catalyzed hydrolysis of esters and aromatic amides.
AB  - We previously reported that DNA catalysts (deoxyribozymes) can hydrolyze DNA
      phosphodiester linkages, but DNA-catalyzed amide bond hydrolysis has been
      elusive. Here we used in vitro selection to identify DNA catalysts that hydrolyze
      ester linkages as well as DNA catalysts that hydrolyze aromatic amides, for which
      the leaving group is an aniline moiety. The aromatic amide-hydrolyzing
      deoxyribozymes were examined using linear free energy relationship analysis. The
      hydrolysis reaction is unaffected by substituents on the aromatic ring (rho ~ 0),
      suggesting general acid-catalyzed elimination as the likely rate-determining step
      of the addition-elimination hydrolysis mechanism. These findings establish that
      DNA has the catalytic ability to achieve hydrolysis of esters and aromatic amides
      as carbonyl-based substrates, and they suggest a mechanism-based approach to
      achieve DNA-catalyzed aliphatic amide hydrolysis. 

PMID- 24127696
TI  - Hydroxymethylfurfural: a possible emergent cause of honey bee mortality?
AB  - Hydroxymethylfurfural (HMF), a common product of hexose degradation occurring
      during the Maillard reaction and caramelization, has been found toxic for rats
      and mice. It could cause a potential health risk for humans due to its presence
      in many foods, sometimes exceeding 1 g/kg (in certain dried fruits and caramel
      products), although the latter still is controversial. HMF can also be consumed
      by honey bees through bad production batches of sugar syrups that are offered as
      winter feeding. In Belgium, abnormal losses of honey bee colonies were observed
      in colonies that were fed with syrup of inverted beet sugar containing high
      concentrations of HMF (up to 475 mg/kg). These losses suggest that HMF could be
      implicated in bee mortality, a topic that so far has received only little
      attention. This paper reviews the current knowledge of the presence of HMF in
      honey bee environment and possible consequences on bee mortality. Some lines of
      inquiry for further toxicological analysis are likewise proposed. 

PMID- 24127697
TI  - Hypoxia promotes danger-mediated inflammation via receptor for advanced glycation
      end products in cystic fibrosis.
AB  - RATIONALE: Hypoxia regulates the inflammatory-antiinflammatory balance by the
      receptor for advanced glycation end products (RAGE), a versatile sensor of damage
      associated molecular patterns. The multiligand nature of RAGE places this
      receptor in the midst of chronic inflammatory diseases. OBJECTIVES: To
      characterize the impact of the hypoxia-RAGE pathway on pathogenic airway
      inflammation preventing effective pathogen clearance in cystic fibrosis (CF) and
      elucidate the potential role of this danger signal in pathogenesis and therapy of
      lung inflammation. METHODS: We used in vivo and in vitro models to study the
      impact of hypoxia on RAGE expression and activity in human and murine CF, the
      nature of the RAGE ligand, and the impact of RAGE on lung inflammation and
      antimicrobial resistance in fungal and bacterial pneumonia. MEASUREMENTS AND MAIN
      RESULTS: Sustained expression of RAGE and its ligand S100B was observed in murine
      lung and human epithelial cells and exerted a proximal role in promoting
      inflammation in murine and human CF, as revealed by functional studies and
      analysis of the genetic variability of AGER in patients with CF. Both hypoxia and
      infections contributed to the sustained activation of the S100B-RAGE pathway,
      being RAGE up-regulated by hypoxia and S100B by infection by Toll-like receptors.
      Inhibiting the RAGE pathway in vivo with soluble (s) RAGE reduced pathogen load
      and inflammation in experimental CF, whereas sRAGE production was defective in
      patients with CF. CONCLUSIONS: A causal link between hyperactivation of RAGE and
      inflammation in CF has been observed, such that targeting pathogenic inflammation
      alleviated inflammation in CF and measurement of sRAGE levels could be a useful
      biomarker for RAGE-dependent inflammation in patients with CF.

PMID- 24127698
TI  - Effect of cognitive training on the expression of brain-derived neurotrophic
      factor in lymphocytes of mild cognitive impairment patients.
AB  - To identify biomarkers associated with cognitive stimulation of mild cognitive
      impairment (MCI) patients, we performed quantitative real-time reverse
      transcriptase polymerase chain reaction for brain-derived neurotrophic factor
      (BDNF) mRNA in peripheral lymphocytes of MCI and healthy subjects undergoing a
      multi-component cognitive training (CT) program. CT determined a significant
      decrease of BDNF mRNA levels in MCI (fold change=0.31) as compared to healthy
      subjects (fold change=0.86). It has been reported that in MCI there is an
      increase of BDNF serum levels, and our findings could indicate a positive effect
      of CT in restoring pre-disease levels of expression.

PMID- 24127699
TI  - Accuracy of tympanic and forehead thermometers in private paediatric practice.
AB  - AIM: To compare infrared tympanic and infrared contact forehead thermometer
      measurements with traditional rectal digital thermometers. METHODS: A total of
      254 children (137 girls) aged one to 24 months (median 7 months) consulting a
      private paediatric practice because of fever were prospectively recruited. Body
      temperature was measured using the three different devices. RESULTS: The median
      and interquartile range for rectal, tympanic and forehead thermometers were 37.6
      (37.1-38.4) degrees C, 37.5 (37.0-38.1) degrees C and 37.5 (37.1-37.9) degrees C,
      respectively (p < 0.01). The limits of agreement in the Bland-Altman plots were 
      0.73 to +1.04 degrees C for the tympanic thermometer and -1.18 to +1.64 degrees C
      for the forehead thermometer. The specificity of both the tympanic and forehead
      thermometers for detecting fever above 38 degrees C was good, but sensitivity was
      low. Forehead measurements were susceptible to the use of a radiant warmer.
      CONCLUSION: Both the tympanic and forehead devices recorded lower temperatures
      than the rectal thermometers. The limits of agreement were particularly wide for
      the forehead thermometer and considerable for the tympanic thermometer. In the
      absence of valid alternatives, because of the ease to use and little degree of
      discomfort, tympanic thermometers can still be used with some reservations.
      Forehead thermometers should not be used in paediatric practice.

PMID- 24127700
TI  - Non-emergency department interventions to reduce ED utilization: a systematic
      review.
AB  - OBJECTIVES: Recent health policy changes have focused efforts on reducing
      emergency department (ED) visits as a way to reduce costs and improve quality of
      care. This was a systematic review of interventions based outside the ED aimed at
      reducing ED use. METHODS: This study was designed as a systematic review. We
      reviewed the literature on interventions in five categories: patient education,
      creation of additional non-ED capacity, managed care, prehospital diversion, and
      patient financial incentives. Studies written in English, with interventions
      administered outside of the ED, and a comparison group where ED use was an
      outcome, were included. Two independent reviewers screened search results using
      MEDLINE, Cochrane, OAIster, or Scopus. The following data were abstracted from
      included studies: type of intervention, study design, population, details of
      intervention, effect on ED use, effect on non-ED health care use, and other
      health and financial outcomes. Quality of individual articles was assessed using
      Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      guidelines. RESULTS: Of 39 included studies, 34 were observational and five were
      randomized controlled trials. Two of five studies on patient education found
      reductions in ED use ranging from 21% to 80%. Out of 10 studies of additional non
      ED capacity, four showed decreases of 9% to 54%, and one a 21% increase. Both
      studies on prehospital diversion found reductions of 3% to 7%. Of 12 studies on
      managed care, 10 had decreases ranging from 1% to 46%. Nine out of 10 studies on
      patient financial incentives found decreases of 3% to 50%, and one a 34%
      increase. Nineteen studies reported effect on non-ED use with mixed results.
      Seventeen studies included data on health outcomes, but 13 of these only included
      data on hospitalizations rather than morbidity and mortality. Seven studies
      included data on cost outcomes. According to the GRADE guidelines, all studies
      had at least some risk of bias, with four moderate quality, one low quality, and
      34 very low quality studies. CONCLUSIONS: Many studies have explored
      interventions based outside the ED to reduce ED use in various populations, with
      mixed evidence. Approximately two-thirds identified here showed reductions in ED
      use. The interventions with the greatest number of studies showing reductions in
      ED use include patient financial incentives and managed care, while the greatest
      magnitude of reductions were found in patient education. These findings have
      implications for insurers and policymakers seeking to reduce ED use.

PMID- 24127701
TI  - HINTS outperforms ABCD2 to screen for stroke in acute continuous vertigo and
      dizziness.
AB  - OBJECTIVES: Dizziness and vertigo account for about 4 million emergency
      department (ED) visits annually in the United States, and some 160,000 to 240,000
      (4% to 6%) have cerebrovascular causes. Stroke diagnosis in ED patients with
      vertigo/dizziness is challenging because the majority have no obvious focal
      neurologic signs at initial presentation. The authors sought to compare the
      accuracy of two previously published approaches purported to be useful in bedside
      screening for possible stroke in dizziness: a clinical decision rule (head
      impulse, nystagmus type, test of skew [HINTS]) and a risk stratification rule
      (age, blood pressure, clinical features, duration of symptoms, diabetes [ABCD2]).
      METHODS: This was a cross-sectional study of high-risk patients (more than one
      stroke risk factor) with acute vestibular syndrome (AVS; acute, persistent
      vertigo or dizziness with nystagmus, plus nausea or vomiting, head motion
      intolerance, and new gait unsteadiness) at a single academic center. All
      underwent neurootologic examination, neuroimaging (97.4% by magnetic resonance
      imaging [MRI]), and follow-up. ABCD2 risk scores (0-7 points), using the
      recommended cutoff of >=4 for stroke, were compared to a three-component eye
      movement battery (HINTS). Sensitivity, specificity, and positive and negative
      likelihood ratios (LR+, LR-) were assessed for stroke and other central causes,
      and the results were stratified by age. False-negative initial neuroimaging was
      also assessed. RESULTS: A total of 190 adult AVS patients were assessed (1999
      2012). Median age was 60.5 years (range = 18 to 92 years; interquartile range
      [IQR] = 52.0 to 70.0 years); 60.5% were men. Final diagnoses were vestibular
      neuritis (34.7%), posterior fossa stroke (59.5% [105 infarctions, eight
      hemorrhages]), and other central causes (5.8%). Median ABCD2 was 4.0 (range = 2
      to 7; IQR = 3.0 to 4.0). ABCD2 >= 4 for stroke had sensitivity of 61.1%,
      specificity of 62.3%, LR+ of 1.62, and LR- of 0.62; sensitivity was lower for
      those younger than 60 years old (28.9%). HINTS stroke sensitivity was 96.5%,
      specificity was 84.4%, LR+ was 6.19, and LR- was 0.04 and did not vary by age.
      For any central lesion, sensitivity was 96.8%, specificity was 98.5%, LR+ was
      63.9, and LR- was 0.03 for HINTS, and sensitivity was 99.2%, specificity was
      97.0%, LR+ was 32.7, and LR- was 0.01 for HINTS "plus" (any new hearing loss
      added to HINTS). Initial MRIs were falsely negative in 15 of 105 (14.3%)
      infarctions; all but one was obtained before 48 hours after onset, and all were
      confirmed by delayed MRI. CONCLUSIONS: HINTS substantially outperforms ABCD2 for
      stroke diagnosis in ED patients with AVS. It also outperforms MRI obtained within
      the first 2 days after symptom onset. While HINTS testing has traditionally been
      performed by specialists, methods for empowering emergency physicians (EPs) to
      leverage this approach for stroke screening in dizziness should be investigated.

PMID- 24127702
TI  - The distribution of the h-index among academic emergency physicians in the United
      States.
AB  - BACKGROUND: Hirsch's h-index (h) attempts to measure the combined academic impact
      and productivity of a scientist by counting the number of publications by an
      author, ranked in descending order by number of citations, until the paper number
      equals the number of citations. This approach provides a natural number or index
      of the number of publications and the number of citations per publication. H was
      first described in physics and was demonstrated to be highly predictive of
      continued academic activity, including recognized measures of scientific
      excellence such as membership in the National Academy of Sciences and being a
      Nobel laureate. Citation rates, research environments, and years of experience
      all affect h, making any comparisons appropriate only for scientists working in
      the same field for a similar time period. The authors are unaware of any report
      describing the distribution of h among academic emergency physicians (AEPs).
      OBJECTIVES: The objective was to describe the distribution of h for AEPs and to
      determine whether Hirsch's demonstration of the h-index as a predictor of
      continued scholarly activity among physicists would also apply to AEPs. METHODS:
      Academic EPs were identified from lists provided on allopathic U.S. emergency
      medicine (EM) residency program websites. "Harzing's Publish or Perish," a free
      program available on the Web that queries Google Scholar, was used to calculate h
      for each AEP. Agreement between raters was analyzed on a subset of 100 EPs. An
      analysis of the 20 EPs with the top h-indices was performed to characterize the
      entire body of their scholarly work, and their h-indices were calculated at 12
      and 24 years into their careers. RESULTS: A total of 4,744 AEPs from 136 programs
      were evaluated. Nine programs did not publicly list the faculty at their
      institutions and were excluded. A linear weighted kappa was used to measure rater
      concordance, with agreement of 98.3% and kappa = 0.92 (95% confidence interval
      [CI] = 0.861 to 0.957). The majority of AEPs had h-indices of zero or one (59%),
      85% had h-indices less than six, 95% less than 13, and 99% less than 24. Ten
      percent of AEPs had h/(years in publication) of 0.5 or greater. For the top 20
      EPs, the mean (+/- standard deviation [+/-SD]) h-index increased from 7.6 (+/
      4.6) to 23.5 (+/-9.4) between years 12 and 24. The mean (+/-SD) increase in h
      index was 15.8 (+/-7.6). CONCLUSIONS: The h-index can be used to characterize the
      academic productivity of AEPs. An h/year of 0.5 or greater is characteristic of
      the most productive EPs and represents only 10% of all AEPs. The 12-year h-index
      of top-performing EPs was strongly related to their future academic productivity.
      The distribution of h among EPs may provide a means for individual investigators
      and academic leaders to evaluate performance and identify EPs with future success
      in EM research.

PMID- 24127703
TI  - Best Evidence in Emergency Medicine (BEEM) rater scores correlate with
      publications' future citations.
AB  - BACKGROUND: The "BEEM" (best evidence in emergency medicine) rater scale was
      created for emergency physicians (EPs) to evaluate the physician-derived clinical
      relevance score of recently published, emergency medicine (EM)-related studies.
      BEEM therefore is designed to help make EPs aware of studies most likely to
      confirm or change current clinical practice. OBJECTIVES: The objective was to
      validate the BEEM rater score as a predictor of literature citation, using a
      bibliometric construct of clinical relevance to EM based on author-, document-,
      and journal-level measures (first and last author h-indices, number of authors
      including corporate and group authors, citations from date of publication to
      2011, and journal impact factor scores) and study characteristics (design,
      category, and sample size). METHODS: Each month from 2007 through 2012,
      approximately 200 EPs from around the world voluntarily reviewed the titles and
      conclusions of recently published EM-related studies identified by BEEM faculty
      via the McMaster Health Information Research Unit. Using the BEEM rater scale, a
      reliable seven-item instrument that evaluates the clinical relevance of studies,
      raters independently assigned BEEM scores to approximately 10 to 20 articles each
      month. Two investigators independently abstracted the bibliometric indices for
      these articles. A citation rate for each article was calculated by dividing the
      Thomson Reuters Web of Science (WoS) total citation count by the number of years
      in publication. BEEM rater scores were correlated with the citation rate using
      Spearman's rho. The performance of the BEEM rater score was assessed for each
      article using negative binomial regression with composite citation count as the
      criterion standard, while controlling for other independent bibliometric
      variables in three models. RESULTS: The BEEM raters evaluated 605 articles with a
      mean (+/-SD) BEEM score of 3.84 (+/-0.7) and a median BEEM score of 3.85
      (interquartile range = 3.38 to 4.30). Articles were primarily therapeutic (59%)
      and diagnostic (27%), with various designs, including 37% systematic reviews, 32%
      randomized controlled trials (RCTs), and 30% observational designs. The citation
      rate and BEEM rater score correlated positively (0.144), while the BEEM rater
      score and the Journal Citation Report (JCR) impact factor score were minimally
      correlated (0.053). In the first model, the BEEM rater score significantly
      predicted WoS citation rate (p < 0.0001) with an odds ratio (OR) of 1.24 (95%
      confidence interval [CI] = 1.106 to 1.402). In subsequent models adjusting for
      the JCR impact factor score, the h-indices of the first and last authors, number
      of authors, and study design, the BEEM rater score was not significant (p =
      0.08). CONCLUSIONS: To the best of our knowledge, the BEEM rater score is the
      only known measure of clinical relevance. It has a high interrater reliability
      and face validity and correlates with future citations. Future research should
      assess this instrument against alternative constructs of clinical relevance.

PMID- 24127704
TI  - Derivation of an abbreviated instrument for use in emergency department low back
      pain research: the five-item Roland Morris Questionnaire.
AB  - OBJECTIVES: Low back pain (LBP) is a common reason for emergency department (ED)
      visits in the United States. Pain and functional outcomes after ED visits for LBP
      tend to be poor. ED-based clinical LBP research is hampered by complexity of
      available outcome instruments, which can be time-consuming to administer. The
      purpose of this investigation was to determine if a shorter version of the well
      validated and commonly used Roland Morris Disability Questionnaire (RMDQ) would
      retain the original 24-item instrument's ability to assess functional outcomes
      accurately in ED patients with LBP. METHODS: The authors used deidentified data
      obtained from a prospective LBP cohort study, which enrolled 674 patients during
      index ED visits for LBP, and followed them by telephone 1 week and 3 months
      later. Five items were selected from the original 24 items of the RMDQ using
      regression techniques. Internal consistency of the abbreviated scale was measured
      using Cronbach's alpha. The strength of association between the five-item scale
      (RM5) and the parent scale was determined at baseline, 1 week, and 3 months. The
      association between change in the parent scale and change in the RM5 and the
      change in RM5 that was most closely associated with a minimum clinically
      significant difference on the RMDQ were also determined. RESULTS: The Cronbach's
      alpha for the RM5 was 0.88 (95% confidence interval [CI] = 0.87 to 0.89) at
      baseline, 0.96 (95% CI = 0.96 to 0.96) at 7 days, and 0.97 (95% CI = 0.97 to
      0.97) at 3 months. The Pearson correlation coefficient for the RM5 versus the
      parent scale was 0.93 (R(2)  = 0.86) at baseline, 0.98 (R(2)  = 0.96) at 1 week,
      and 0.98 (R(2)  = 0.96) at 3 months. The correlations between change from
      baseline in the abbreviated scale and the parent scale were 0.95 (R(2)  = 0.90)
      and 0.96 (R(2)  = 0.92) at 7 days and 3 months, respectively. A one-point change
      in the RM5 has a sensitivity of 96% (95% CI = 93% to 98%) and a specificity of
      92% (95% CI = 89% to 94%) for the minimum clinically significant change on the
      RMDQ. CONCLUSIONS: An abbreviated five-item version of the RMDQ was developed.
      Pending independent validation, this shortened instrument should streamline ED
      based low back pain research.

PMID- 24127705
TI  - Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in
      a rat model.
AB  - OBJECTIVES: The anticoagulant dabigatran has no reversal agent and may cause life
      threatening bleeding in patients with trauma or closed-space hemorrhage.
      Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in
      serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its
      anticoagulant effects are concentration dependent. The study objective was to
      determine if ILE therapy reverses dabigatran's anticoagulant effects. METHODS:
      Twenty rats were selected at random, 10 in the ILE group and 10 in a normal
      saline (NS) control group. Animals had a baseline tail bleeding time (T0),
      followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a
      second tail bleed time measurement was performed, followed by a 7-minute infusion
      of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was
      obtained. An ILE-only group of five animals had bleeding times assessed prior to
      (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures
      analysis of variance modeling the effect of time, group, and the interaction of
      group and time on bleed times was conducted. RESULTS: There was a significant
      within-subject change in bleeding time across the assessment points (F(2,36) =
      33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or
      an interaction between group and assessment point on mean bleeding time (F(2,36)
      = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5
      seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95%
      CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control
      group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5
      seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55
      seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average
      bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased
      significantly at T15 to 237 seconds (95% CI = 161 to 313 seconds; p = 0.02).
      CONCLUSIONS: The anticoagulant effects of dabigatran are not reversed with ILE
      therapy. Although ILE itself significantly prolonged bleeding times, when
      administered to dabigatran-anticoagulated rats, bleeding times did not change
      significantly. There may be a complex interaction of ILE with dabigatran that
      this study was not able to elucidate.

PMID- 24127706
TI  - When coverage expands: children's health insurance program as a natural
      experiment in use of health care services.
AB  - BACKGROUND: Expanding insurance coverage is designed to improve access to primary
      care and reduce use of emergency department (ED) services. Whether expanding
      coverage achieves this is of paramount importance as the United States prepares
      for the Affordable Care Act. OBJECTIVES: Emergency and outpatient department use
      was examined after the State Children's Health Insurance Program (CHIP) coverage
      expansion, focusing on adolescents (a major target group for CHIP) versus young
      adults (not targeted). The hypothesis was that coverage would increase use of
      outpatient services, and ED use would decrease. METHODS: Using the National
      Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory
      Medical Care Survey (NHAMCS), the years 1992-1996 were analyzed as baseline and
      then compared to use patterns in 1999-2009, after the CHIP launch. Primary
      outcomes were population-adjusted annual visits to ED versus nonemergency
      outpatient settings. Interrupted time series were performed on use rates to ED
      and outpatient departments between adolescents (11 to 18 years old) and young
      adults (19 to 29 years old) in the pre-CHIP and CHIP periods. Outpatient-to-ED
      ratios were calculated and compared across time periods. A stratified analysis by
      payer and sex was also performed. RESULTS: The mean number of outpatient
      adolescent visits increased by 299 visits per 1,000 persons (95% confidence
      interval [CI] = 140 to 457), while there was no statistically significant
      increase in young adult outpatient visits across time periods. There was no
      statistically significant change in the mean number of adolescent ED visits
      across time periods, while young adult ED use increased by 48 visits per 1,000
      persons (95% CI = 24 to 73). The adolescent outpatient-to-ED ratio increased by
      1.0 (95% CI = 0.49 to 1.6), while the young adults ratio decreased by 0.53 across
      time periods (95% CI = -0.90 to -0.16). CONCLUSIONS: Since CHIP, adolescent non
      ED outpatient visits have increased, while ED visits have remained unchanged. In
      comparison to young adults, expanding insurance coverage to adolescents improved
      use of health care services and suggests a shift to non-ED settings. Expanding
      insurance through the Affordable Care Act of 2010 will likely increase use of
      outpatient services, but may not decrease ED volumes.

PMID- 24127708
TI  - Parental anxiety at initial acute presentation is not associated with prolonged
      symptoms following pediatric concussion.
AB  - OBJECTIVES: Anxiety modulates symptom perception in adults following concussion,
      prolonging the time to full recovery. The authors sought to determine whether
      parental anxiety was associated with persistent postconcussive symptoms (PCS) in
      their children following concussion. METHODS: A prospective observational cohort
      with 98 children aged 5 to 17 years following concussion participated from a
      tertiary pediatric emergency department (ED). The main exposure was parental
      anxiety at the time of acute presentation following pediatric concussion,
      measured using the self-administered, validated Spielberger State-Trait Anxiety
      Inventory-State Anxiety Scale (STAI-S). The primary outcome measured was presence
      of PCS in the child at 1 month, per the validated Post-Concussive Symptom
      Inventory (PCSI). Secondary outcome measures included parental anxiety score over
      time, school absenteeism, and return to sports. Data were collected during the
      initial ED visit and at 3-day, 7-day, 2-week, 1-month, and 3-month follow-ups.
      RESULTS: Of 98 children enrolled, 27% (95% confidence interval [CI] = 19% to 36%)
      developed PCS at 1 month. No significant associations were detected between
      parental anxiety at the index visits and the number of previous pediatric
      concussions (p = 0.73), sex (p = 0.61), loss of consciousness (p = 0.43), history
      of migraines (p = 0.31), or history of anxiety diagnosed in the patients (p =
      0.09). A significant association was noted between patient diagnosis of attention
      deficit hyperactivity disorder (ADHD) and parental anxiety at the index visits (p
      = 0.001). Parental anxiety at acute presentation was not associated with
      children's prolonged symptoms at 1 month (p = 0.63). Parental anxiety remained
      elevated in parents whose children had prolonged symptoms compared to those
      parents whose children's symptoms resolved (median = 30, interquartile range
      [IQR] = 22 to 44; and median = 21, IQR = 20 to 25, respectively; p < 0.001).
      Initial parental anxiety presentation was not associated with school absenteeism
      (p = 0.23) or not returning to sport or gym class (p = 0.89). There were no
      significant effects involving ADHD alone (p = 0.44) or together with baseline
      parental anxiety (p = 0.36 for ADHD and p = 0.55 for anxiety) using logistic
      regression analysis to examine potential predictive effects of child's ADHD
      combined with parental anxiety at the index visit on persistent symptoms at 1
      month. CONCLUSIONS: Parental anxiety at time of acute presentation does not
      appear to be associated with prolongation of postconcussive symptoms in their
      children. However, parents of persistently symptomatic children remain
      significantly more anxious than those whose children's symptoms have resolved.
      Future research should attempt to reduce the familial burden of concussion
      through expectation management strategies.

PMID- 24127707
TI  - U.S. trends in computed tomography use and diagnoses in emergency department
      visits by patients with symptoms suggestive of pulmonary embolism, 2001-2009.
AB  - OBJECTIVES: Using computed tomography (CT) to evaluate patients with chest
      symptoms is common in emergency departments (EDs). This article describes recent
      trends of CT use in U.S. EDs for patients presenting with symptoms common to
      acute pulmonary embolism (PE). METHODS: The 2001-2009 National Hospital
      Ambulatory Medical Care Survey (NHAMCS), a nationally representative survey of
      U.S. ED encounters, was used for data collection. Patients with at least one of
      three complaints (chest pain, dyspnea, or hemoptysis) were categorized into the
      chest symptom study (CSS) group. The yearly increases in CT use for the
      complaints were tabulated first, then linear regression analysis was used to
      calculate average rates of increases in CT use between 2001 and 2007, the years
      where CT use increased, for the overall population and among specific subgroups.
      The ratios of the number of visits when CT was ordered and there was a target
      diagnosis relative to the total number of visits with CT in the CSS group
      (diagnosis/CT ratio) were calculated for PE and pneumonia. RESULTS: Annual CT
      rates for the CSS group increased from 2.6% in 2001 to 13.2% in 2007,
      subsequently leveling off at approximately 12.5% in 2008 and 2009. The average
      growth rate of CT use for the CSS group was 28.1% (95% confidence interval [CI] =
      20.9% to 35.7%) per year between 2001 and 2007. Testing rates for all subgroups
      increased. The lowest growth rate was among Hispanic patients, whose CT rates
      grew 14.2% (95% CI = 5.7% to 23.5%) per year. The highest growth rate was in
      nonurban hospitals, at 43.1% (95% CI = 15.2% to 77.8%) per year. Patients triaged
      as nonurgent received the fewest CTs, compared to those who should be seen in 2
      hours or less. With regard to sources of payment, the self-pay subgroup
      experienced the highest rate of increase at 35.1% (95% CI = 18.6% to 53.9%). The
      PE diagnosis/CT ratio from 2002 to 2009 was 2.7% for the CSS group. The pneumonia
      diagnosis/CT ratio grew from 5.8% in 2002 to 2005 to 7.8% in 2006 to 2009.
      CONCLUSIONS: Computed tomography use in ED visits by patients with chest symptoms
      increased dramatically from 2001 to 2007 and seems to have leveled off in
      subsequent years. The low PE diagnosis-to-CT ratio suggests that EDs may need to
      promote evidence-based use of CT.

PMID- 24127709
TI  - Intranasal ketamine for analgesia in the emergency department: a prospective
      observational series.
AB  - OBJECTIVES: The objective was to examine the feasibility, effectiveness, and
      adverse effect profile of intranasal ketamine for analgesia in emergency
      department (ED) patients. METHODS: This was a prospective observational study
      examining a convenience sample of patients aged older than 6 years experiencing
      moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or
      greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores
      were recorded on a standard 100-mm VAS by trained investigators at baseline, then
      every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30
      minutes. The primary outcome was the number and proportion of patients
      experiencing clinically significant reductions in VAS pain scores, defined as VAS
      reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the
      median reduction in VAS, the median time required to achieve a 13 mm reduction in
      VAS, vital sign changes, and adverse events. Continuous data are reported with
      medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used
      to assess changes in VAS scores. Adverse effects are reported with proportions
      and 95% confidence intervals (CIs). RESULTS: Forty patients were enrolled with a
      median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for
      primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30
      minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes
      was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5
      minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse
      effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95%
      CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%),
      nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%;
      95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to
      13%). All adverse effects were transient and none required intervention. There
      were no changes in vital signs requiring clinical intervention. CONCLUSIONS:
      Intranasal ketamine reduced VAS pain scores to a clinically significant degree in
      88% of ED patients in this series. Adverse effects were minor and transient.
      Intranasal ketamine may have a role in the provision of effective, expeditious
      analgesia to ED patients.

PMID- 24127710
TI  - Emergency medicine residents' self-assessments play a critical role when
      receiving feedback.
AB  - OBJECTIVES: Emergency medicine (EM) faculty often aim to improve resident
      performance by enhancing the quality and delivery of feedback. The acceptance and
      integration of external feedback is influenced by multiple factors. However, it
      is interpreted through the "lens" of the learner's own self-assessment. Ideally,
      following an educational activity with feedback, a learner should be able to
      generate and act upon specific learning goals to improve performance. Examining
      the source of generated learning goals, whether from one's self-assessment or
      from external feedback, might shed light on the factors that lead to improvement
      and guide educational initiatives. Using a standard oral board scenario, the
      objective of this study was to determine the effects that residents' self
      assessment and specific feedback from faculty have on not only the generation of
      learning goals but also the execution of these goals for performance improvement.
      METHODS: In this cross-sectional educational study at four academic programs, 72
      senior EM residents participated in a standardized oral board scenario. Following
      the scenario, residents completed a self-assessment form. Next, examiners used a
      standardized checklist to provide both positive and negative feedback.
      Subsequently, residents were asked to generate "SMART" learning goals (specific,
      measurable, attainable, realistic, and time-bound). The investigators categorized
      the learning goals as stemming from the residents' self-assessments, feedback, or
      both. Within 4 weeks, the residents were asked to recall their learning goals and
      describe any actions taken to achieve those goals. These were grouped into
      similar categories. Descriptive statistics were used to summarize the data.
      RESULTS: A total of 226 learning goals were initially generated (mean +/- SD =
      3.1 +/- 1.3 per resident). Forty-seven percent of the learning goals were
      generated by the residents' self-assessments only, while 27% were generated by
      the feedback given alone. Residents who performed poorly on the case incorporated
      feedback more often than high performers when generating learning goals. Follow
      up data collection showed that 62 residents recalled 89 learning goals, of which
      52 were acted upon. On follow-up, the numbers of learning goals from self
      assessment and feedback were equal (25% each, 13 of 52), while the greatest
      number of reportedly executed learning goals came from self-assessments and
      feedback in agreement (40%). CONCLUSIONS: Following feedback on an oral board
      scenario, residents generated the majority of their learning goals from their own
      self-assessments. Conversely, at the follow-up period, they recalled an increased
      number of learning goals stemming from feedback, while the largest proportion of
      learning goals acted upon stemmed from both feedback and self-assessments in
      agreement. This suggests that educators need to incorporate residents' self
      assessments into any delivered feedback to have the greatest influence on future
      learning goals and actions taken to improve performance.

PMID- 24127711
TI  - Reducing emergency department utilization: is this the answer?

PMID- 24127712
TI  - Diagnosing dizziness: we are teaching the wrong paradigm!

PMID- 24127713
TI  - Promoting stewardship of academic productivity in emergency medicine: using the h
      index to advance beyond the impact factor.

PMID- 24127714
TI  - Early serum acetaminophen levels: how soon is too soon?

PMID- 24127715
TI  - Negative predictive value of acetaminophen concentrations within four hours of
      ingestion.
AB  - OBJECTIVES: The objective was to ascertain whether acetaminophen (APAP)
      concentrations less than 100 MUg/mL obtained between 1 and 4 hours after acute
      ingestion accurately predict a nontoxic 4-hour concentration. METHODS: The
      authors performed a multicenter, prospective cohort study involving five
      emergency departments (EDs) participating in the ToxIC Research Network. Data
      were collected from May 2009 to December 2011. Patients with APAP concentrations
      <100 MUg/mL drawn between 1 and 4 hours after acute ingestions, and
      concentrations drawn 4 or more hours after ingestions, were included in the
      study. Exclusion criteria included initial concentration >100 MUg/mL, initial
      APAP concentration drawn prior to 1 hour, two undetectable APAP concentrations,
      the second concentration drawn prior to 4 hours, and unknown time of ingestion.
      Toxic concentrations 4 or more hours after ingestion were defined as
      concentrations that plotted above the 150 MUg/mL line on the Rumack-Matthew
      nomogram. RESULTS: Data were collected on 83 patients who met inclusion criteria.
      Of the 83 patients with APAP concentrations <100 MUg/mL between 1 and 4 hours,
      one patient (1.2%) had a >= 4-hour toxic concentration. Negative predictive value
      (NPV) for an APAP concentration <100 MUg/mL obtained between 1 and 4 hours after
      an acute ingestion was 98.8% (95% confidence interval [CI] = 93.5% to 99.8%).
      CONCLUSIONS: An APAP concentration of <100 MUg/mL obtained between 1 and 4 hours
      after ingestion has a high NPV for excluding toxic ingestion. We do not recommend
      reliance on concentrations obtained between 1 and 4 hours to exclude toxicity,
      because of a potential false-negative rate of 6.5%.

PMID- 24127716
TI  - Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in
      rabbit clomipramine toxicity.
AB  - OBJECTIVES: Liposome (LIP)-like lipid dispersions have emerged as useful
      detoxification vehicles in vitro. The authors compare resuscitation with tailored
      LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a
      rabbit model of clomipramine toxicity. METHODS: Sedated, instrumented New Zealand
      white rabbits underwent clomipramine infusion at 3.2 mg/kg/min to 50% baseline
      mean arterial pressure (MAP) and then at 1.6 mg/kg/min for 30 minutes. BIC (3
      mL/kg 8.4%), ILE (3 mL/kg 20%), or LIP (24 mg/kg) were infused as rescue
      treatments at toxicity and were repeated at 10 minutes (n = 5 in each group).
      RESULTS: Thirty-minute MAP was greatest in ILE-treated animals: 61 mm Hg ILE
      (interquartile range [IQR] = 49 to 64 mm Hg), 43 mm Hg LIP (IQR = 36.5 to 49 mm
      Hg), and 10 mm Hg BIC (IQR = 10 to 44 mm Hg; all p = 0.02). Two of the five BIC
      treated animals survived to 30 minutes, compared with all five of the ILE-treated
      animals and all five of the LIP-treated animals (p = 0.044). CONCLUSIONS: Both
      ILE and LIPs improved hemodynamic recovery compared with bicarbonate in
      clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was
      observed in the ILE group.

PMID- 24127717
TI  - Near-infrared spectroscopy assessment of tissue saturation of oxygen in torsed
      and healthy testes.
AB  - OBJECTIVES: The objective was to assess whether testicular torsion is associated
      with low testicular tissue saturation of oxygen (StO2 ) as measured by
      transscrotal near-infrared spectroscopy (NIRS) and to compare the differences in
      NIRS values between testicles of the same patient, both in patients with
      testicular torsion and in healthy controls. METHODS: This was an observational
      study of healthy controls and patients with surgically confirmed testicular
      torsion who were recruited from males under 30 years of age presenting to the
      emergency department (ED). The hypothesis was that the difference in NIRS values
      for the control's two testicles would be zero, and that the difference between
      the torsed and healthy testicles on an individual patient would not be zero.
      Based on animal data, the study was powered to detect an absolute difference of
      StO2 of 47%. RESULTS: The mean StO2 for the left control patients' testicles was
      73.6% (95% confidence interval [CI] = 68.0% to 79.1%) and the mean StO2 for the
      right controls' testicles for controls was 73.6% (95% CI = 66.9% to 80.4%; n =
      17). The absolute difference in NIRS StO2 for left minus right for each
      individual was 3.5% (95% CI = 1.8% to 5.4%), which was significantly different (p
      = 0.0007), and refuted the hypothesis that there was no significant difference in
      StO2 between left and right testes in healthy patients. In the testicular torsion
      group, the torsed side had a mean StO2 of 82.8% (95% CI = 68.7% to 96.9%), and
      the contralateral nontorsed testes had a mean of 85.8% (95% CI = 72.3% to 99.3%).
      The mean StO2 difference, nontorsed minus torsed was 3.0% (range = -1% to 9%, 95%
      CI = -2% to 8%; p = 0.174), refuting the hypothesis that torsed testes would
      demonstrate significantly lower values for StO2 . CONCLUSIONS: While pilot animal
      investigations support a potential role for transscrotal NIRS for the detection
      of testicular torsion, this first clinical translation of animal findings reveals
      that the investigated, transcutaneous, reflectance geometry NIRS device failed to
      demonstrate symmetric oxygenation of left and right testes in healthy controls
      and also failed to demonstrate depressed tissue saturation of oxygen values in
      patients with confirmed testicular torsion. While limited by a small sample size,
      other problems such as inability to calibrate depth of measurement of StO2 may
      have led to falsely elevated readings in patients with torsion.

PMID- 24127720
TI  - The vanishing target sign: confirmation of intraluminal needle position for
      ultrasound guided vascular access.

PMID- 24127721
TI  - Diagnostic and prognostic value of circulating tumor-related DNA in cancer
      patients.
AB  - Qualitative and quantitative analysis of circulating cell-free DNA (cfDNA) is an
      emerging non-invasive blood biomarker utilized to assess tumor progression and to
      evaluate prognosis, diagnosis and response to treatment. There is a need to
      develop cfDNA biomarkers to avoid complex risk-prone biopsy procedures for
      primary or metastatic tumors. Given the challenges associated with inter- and
      intra-tumor heterogeneity, the implementation of genome-wide cfDNA analysis will
      become an important avenue to understand tumor progression and therapeutic
      settings, not only for predominant, but also for under-represented tumor
      subclones with specific genomic aberrations. We summarize the latest publications
      in cfDNA analysis, including a metric analysis of clinical trials and new high
      throughput technology applied to cfDNA analysis in clinical oncology. 

PMID- 24127723
TI  - Engineering a hollow nanocontainer platform with multifunctional molecular
      machines for tumor-targeted therapy in vitro and in vivo.
AB  - In order to selectively target malignant cells and eliminate severe side effects
      of conventional chemotherapy, biocompatible and redox-responsive hollow
      nanocontainers with tumor specificity were fabricated. The mechanized
      nanocontainers were achieved by anchoring mechanically interlocked molecules,
      i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles
      via disulfide bonds as intermediate linkers for intracellular glutathione
      triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food
      and Drug Administration approved tetraethylene glycol chains, alpha-cyclodextrin,
      and folic acid. In this study, folate groups on the mechanized hollow
      nanocontainers act as both the tumor-targeting agents and stoppers of the
      [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin
      loaded mechanized nanocontainers could selectively induce the apoptosis and death
      of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability
      to tumor tissues in vitro and inhibited the tumor growth with minimal side
      effects in vivo. The present controlled and targeted drug delivery system paves
      the way for developing the next generation of nanotherapeutics toward efficient
      cancer treatment. 

PMID- 24127724
TI  - Investigating the role of (2S,4R)-4-hydroxyproline in elastin model peptides.
AB  - Post-translational modifications play a key role in defining the biological
      functions of proteins. Among them, the hydroxylation of proline producing the
      (2S,4R)-4-hydroxyproline (Hyp) is one of the most frequent modifications observed
      in vertebrates, being particularly abundant in the proteins of the extracellular
      matrix. In collagen, hydroxylation of proline plays a critical role, conferring
      the correct structure and mechanical strength to collagen fibers. In elastin, the
      exact role of this modification is not yet understood. Here we show that Hyp
      containing elastin polypeptides have flexible molecular structures, analogously
      to proline-containing polypeptides. In turn, the self-assembly of the elastin
      peptides is significantly altered by the presence of Hyp, evidencing different
      supramolecular structures. Also the in vitro susceptibility to protease digestion
      is changed. These findings give a better insight into the elastic fiber formation
      and degradation processes in the extracellular matrix. Furthermore, our results
      could contribute in defining the subtle role of proline structural variants in
      the folding and self-assembly of elastin-inspired peptides, helping the rational
      design of elastin biomaterials. 

PMID- 24127725
TI  - Molecular cloning of type I collagen cDNA and nutritional regulation of type I
      collagen mRNA expression in grass carp.
AB  - Grass carp (Ctenopharyngodon idellus) are important Chinese freshwater fish, and
      in China, the faba bean has been used as the sole food source for grass carp to
      transform them into crisp grass carp. Because of this, crisp grass carp has
      become an economically important fish because of its increased muscle hardness.
      To study the nutritional regulation of type I collagen in faba bean-fed grass
      carp, we isolated type I collagen alpha 2 (COL1A2) on the basis of our isolation
      of COL1A1. The COL1A2 cDNA was found to be 4899 bp in length and included a 4059
      bp coding sequence (CDS) and encoded a polypeptide of 1352 AA. The protein
      peptide molecular weight was 127.39 kD, and the theoretical isoelectric point was
      9.37. The COL1A2 protein possessed five alpha-helixes, eight beta-sheets, 16
      regions of triple helical repeats, 21 low-complexity regions, 10 function domains
      and two zinc-binding sites; however, no calcium-binding sites were observed. The
      mRNA expression of COL1A1 and COL1A2 was assessed in eight tissues (muscle,
      hepatopancreas, intestine, gills, skin, fin, kidney and spleen) from grass carp
      and crisp grass carp by semi-quantitative RT-PCR. Expression of COL1A1 in the
      muscle, intestines and skin of crisp grass carp was higher than that in grass
      carp, and expression of COL1A2 in the muscle, gills, fin and skin of crisp grass
      carp was higher than that in grass carp. In the muscle of crisp grass carp,
      expression of COL1A1 and COL1A2 was higher than that in grass carp, which was
      further confirmed by real-time PCR, and collagen content also was enhanced. These
      results demonstrated that type I collagen was closely related to the increased
      muscle hardness of faba bean-fed grass carp. 

PMID- 24127726
TI  - The conformational landscape of an intrinsically disordered DNA-binding domain of
      a transcription regulator.
AB  - Delineating the conformational features of intrinsically disordered proteins
      (IDPs) is an area of work that challenges current experimental and simulation
      protocols. It is therefore imperative to combine multiple methodologies to arrive
      at a coherent picture of the heterogeneous IDP ensembles. Here, we present a
      comprehensive study drawing from structure-based statistical mechanical model,
      explicit-solvent MD and implicit-solvent REMD simulations, and mutational
      analysis to characterize, in combination with experimental observables, the
      functional landscape of the intrinsically disordered DNA-binding domain (DBD) of
      the Escherichia coli transcription regulator CytR in its free-state. The
      resulting landscape of CytR DBD populates multiple distinct conformations and
      shows signs of residual frustration from native interactions that are critical
      for promoting partial structure in the DNA-binding second helix. We thus find
      evidence for a unique combination of conformational selection and induced-fit
      mechanism that enables CytR to bind DNA. Functionally deficient mutations affect
      the IDP landscape in a nontrivial manner highlighting the importance of using an
      ensemble-based structural representation of IDPs. In effect, our results reveal a
      functional role for structural frustration, and provide a novel avenue to
      characterize IDP landscapes combining simple structural probes and multimodel
      approaches. 

PMID- 24127722
TI  - Practitioner review: maternal mood in pregnancy and child development-
      implications for child psychology and psychiatry.
AB  - BACKGROUND: The empirical base suggesting a link between prenatal maternal
      anxiety, stress or depression and cognitive, behavioral, and biological outcomes
      in the infant and child has increased dramatically in the past 10 years. METHODS:
      In this review, we consider the relevance of prenatal maternal mood for child
      mental health practitioners; the empirical base for a likely causal impact of the
      link between prenatal anxiety, depression, or stress and child outcomes; the
      degree to which the available evidence is sufficient for informing or altering
      clinical practice; and the possible role of prenatal interventions for promoting
      child health and development. A selective review of PubMed, Cochrane Library and
      other sources was undertaken. FINDINGS: Clinically significant links between
      maternal prenatal distress and child behavioral and cognitive outcomes have been
      reported; predictions to stress physiology, immunology, and neurodevelopment have
      been reported but the effect sizes and clinical significance is less clear.
      Several candidate mechanisms have been proposed, with some supporting evidence.
      Many behavioral treatments for prenatal maternal distress exist, but their
      application to promoting child health is largely unknown. CONCLUSIONS: Research
      on maternal prenatal distress is a good example of translational research and
      offers a strong paradigm for promoting interdisciplinary clinical research on
      child health and development.

PMID- 24127727
TI  - Immune response involving the bulge region in addition to telogen conversion
      contributes to hair loss in a case of atypical drug-induced hypersensitivity
      syndrome.

PMID- 24127728
TI  - A systematic review of ordinal scales used to classify the eating and drinking
      abilities of individuals with cerebral palsy.
AB  - AIM: The aim of this review was to examine systematically the scope, validity,
      and reliability of ordinal scales used to classify the eating and drinking
      ability of people with cerebral palsy (CP). METHOD: Six electronic databases were
      searched to identify measures used to classify eating and drinking ability; in
      addition, two databases were used to track citations of key texts. The constructs
      assessed by each measure were examined in relation to the World Health
      Organization International Classification of Functioning, Disability and Health.
      Evidence of validity and reliability of the identified scales was appraised from
      peer-reviewed studies using standard criteria. RESULTS: Fifteen scales were
      identified in 23 papers. Clinician or researcher assessment was required for 13
      scales; nine scales made use of information from parents and carers through
      interviews or questionnaires. Eight scales used the terms mild, moderate, and
      severe (with varying definitions) to describe different aspects of eating and
      drinking impairment. There was an assessment of either content validity and/or
      reliability for five scales; however, none met the recommended psychometric
      quality standards. INTERPRETATION: Currently, there is a lack of evidence of the
      validity and reliability of ordinal scales of functional eating and drinking
      abilities of people with CP.

PMID- 24127729
TI  - Narrative processing in typically developing children and children with early
      unilateral brain injury: seeing gesture matters.
AB  - Narrative skill in kindergarteners has been shown to be a reliable predictor of
      later reading comprehension and school achievement. However, we know little about
      how to scaffold children's narrative skill. Here we examine whether the quality
      of kindergarten children's narrative retellings depends on the kind of narrative
      elicitation they are given. We asked this question with respect to typically
      developing (TD) kindergarten children and children with pre- or perinatal
      unilateral brain injury (PL), a group that has been shown to have difficulty with
      narrative production. We compared children's skill in retelling stories
      originally presented to them in 4 different elicitation formats: (a) wordless
      cartoons, (b) stories told by a narrator through the auditory modality, (c)
      stories told by a narrator through the audiovisual modality without co-speech
      gestures, and (e) stories told by a narrator in the audiovisual modality with co
      speech gestures. We found that children told better structured narratives in
      response to the audiovisual + gesture elicitation format than in response to the
      other 3 elicitation formats, consistent with findings that co-speech gestures can
      scaffold other aspects of language and memory. The audiovisual + gesture
      elicitation format was particularly beneficial for children who had the most
      difficulty telling a well-structured narrative, a group that included children
      with larger lesions associated with cerebrovascular infarcts.

PMID- 24127730
TI  - Investigation of poorer bladder cancer survival in women in NSW, Australia: a
      data linkage study.
AB  - OBJECTIVE: To investigate the associations of a range of personal and clinical
      variables with bladder cancer survival in men and women in NSW to see if we could
      explain why bladder cancer survival is consistently poorer in women than in men.
      PATIENTS AND METHODS: All 6880 cases of bladder cancers diagnosed in NSW between
      2000 and 2008 were linked to hospital separation data and to deaths. Separate Cox
      proportional hazards regression models of hazard of bladder cancer death were
      constructed for those who did or did not undergo cystectomy. RESULTS: A total of
      16% of patients with bladder cancer underwent cystectomy (16% of men and 15% of
      women). Women who underwent cystectomy were 26% more likely to die than men
      (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.59) after adjustment
      for age, stage, time from diagnosis to cystectomy, distance from treatment
      facility and country of birth. None of the above covariates had a material effect
      on the difference in hazard between women and men; however, when stratified by a
      history of cystitis, the adjusted hazard was 55% higher in women (HR 1.55, 95% CI
      1.15-2.10) than in men with a history of cystitis while, in the absence of this
      history, there was no difference in the hazard between men and women (HR 0.99,
      95% CI 0.57-1.70). This apparent modification of the effect of sex on bladder
      cancer outcome was not seen in patients treated only by resection: the adjusted
      HRs in women relative to men were 1.10 (95% CI 0.92-1.31) in those with a history
      of cystitis and 1.21 (95% CI 0.98-1.50) in those without. A history of haematuria
      did not modify appreciably the association of sex with bladder cancer outcome.
      CONCLUSION: Women's poorer survival from bladder cancer compared with that of men
      remains unexplained; however, the possibility that some factor associated with a
      history of cystitis may contribute to or explain the poorer outcome in women
      merits further investigation.

PMID- 24127731
TI  - Deeper understanding of biological tissue: quantitative correlation of MALDI-TOF
      and Raman imaging.
AB  - In order to achieve a comprehensive description of biological tissue, spectral
      information about proteins, lipids, nucleic acids, and other biochemical
      components need to be obtained concurrently. Different analytical techniques may
      be combined to record complementary information of the same sample. Established
      techniques, which can be utilized to elucidate the biochemistry of tissue samples
      are, for instance, MALDI-TOF-MS and Raman microscopic imaging. With this
      contribution, we combine these two techniques for the first time. The combination
      of both techniques allows the utilization and interpretation of complementary
      information (i.e., the information about the protein composition derived from the
      Raman spectra with data of the lipids analyzed by the MALDI-TOF measurements).
      Furthermore, we demonstrate how spectral information from MALDI-TOF experiments
      can be utilized to interpret Raman spectra. 

PMID- 24127732
TI  - Triangular exchange interaction patterns in K3Fe6F19: an iron potassium fluoride
      with a complex tungsten bronze related structure.
AB  - The synthesis and structural and magnetic characterizations of K3Fe6F19, a new
      iron potassium fluoride with a complex tungsten bronze related structure, are
      presented. This phase was found during the investigation of relatively low
      temperature (600  degrees C) synthesis conditions of classical tetragonal
      tungsten bronze (TTB) fluorides and can be considered an intermediate that forms
      at this temperature owing to faster crystallization kinetics. The K3Fe6F19
      compound has an orthorhombic structure (space group Cmcm (63), a = 7.6975(3) A, b
      = 18.2843(7) A, c = 22.0603(9) A) related to the TTB one, where the perovskite
      cage is substituted by a large S-shaped channel simultaneously occupied by two
      potassium atoms. The magnetic structure, characterized by magnetization
      measurements on an oriented single crystal and powder neutron diffraction, is
      dominated by the presence of interconnected double stripes of antiferromagnetic
      triangular exchange interaction patterns alternately rotated in clock- and
      anticlockwise fashion. The magnetic order takes place in a wide temperature
      range, by increasing progressively the interaction dimensionality. 

PMID- 24127733
TI  - A comparison in dogs of medetomidine, with or without MK-467, and the combination
      acepromazine-butorphanol as premedication prior to anaesthesia induced by
      propofol and maintained with isoflurane.
AB  - OBJECTIVE: To compare the haemodynamic effects of three premedicant regimens
      during propofol-induced isoflurane anaesthesia. STUDY DESIGN: Prospective,
      randomized cross-over study. ANIMALS: Eight healthy purpose-bred beagles aged 4
      years and weighing mean 13.6 +/- SD 1.9 kg. METHODS: The dogs were instrumented
      whilst under isoflurane anaesthesia prior to each experiment, then allowed to
      recover for 60 minutes. Each dog was treated with three different premedications
      given intravenously (IV): medetomidine 10 MUg kg-1 (MED), medetomidine 10 MUg kg
      1 with MK-467 250 MUg kg-1 (MMK), or acepromazine 0.01 mg kg-1 with butorphanol
      0.3 mg kg-1 (AB). Anaesthesia was induced 20 minutes later with propofol and
      maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac
      output, arterial blood pressures (ABP), central venous pressure (CVP),
      respiratory rate, inspired oxygen fraction, rectal temperature (RT) and
      bispectral index (BIS) were measured and arterial and venous blood gases
      analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen
      delivery index (DO2 I), systemic oxygen consumption index (VO2 I) and oxygen
      extraction (EO2) were calculated. Times to extubation, righting, sternal
      recumbency and walking were recorded. The differences between treatment groups
      were evaluated with repeated measures analysis of covariance. RESULTS: HR, CI,
      DO2 I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI,
      EO2, RT and arterial lactate were significantly higher with MED than with MMK and
      AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI,
      SVRI, DO2 I, VO2 I, EO2, T, BIS and blood lactate did not differ significantly
      between MMK and AB. The times to extubation, righting, sternal recumbency and
      walking were significantly shorter with MMK than with MED and AB. CONCLUSIONS AND
      CLINICAL RELEVANCE: MK-467 attenuates certain cardiovascular effects of
      medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of
      MMK are very similar to those of AB.

PMID- 24127734
TI  - Spin transfer torque in a graphene lateral spin valve assisted by an external
      magnetic field.
AB  - Spin-based devices are widely discussed for post-complementary metal-oxide
      semiconductor (CMOS) applications. A number of spin device ideas propose using
      spin current to carry information coherently through a spin channel and
      transfering it to an output magnet by spin transfer torque. Graphene is an ideal
      channel material in this context due to its long spin diffusion length, gate
      tunable carrier density, and high carrier mobility. However, spin transfer torque
      has not been demonstrated in graphene or any other semiconductor material as of
      yet. Here, we report the first experimental measurement of spin transfer torque
      in graphene lateral nonlocal spin valve devices. Assisted by an external magnetic
      field, the magnetization reversal of the ferromagnetic receiving magnet is
      induced by pure spin diffusion currents from the input magnet. The magnetization
      switching is reversible between parallel and antiparallel configurations,
      depending on the polarity of the applied charged current. The presented results
      are an important step toward developing graphene-based spin logic and
      understanding spin-transfer torque in systems with tunneling barriers. 

PMID- 24127735
TI  - NSAID-sparing effect of glucosamine hydrochloride in patients with knee
      osteoarthritis: an analysis of data from a French database.
AB  - OBJECTIVE: Knee osteoarthritis (OA) is a major cause of pain, functional
      limitation, and reduced quality-of-life, particularly in older adults. This study
      evaluated the 'real world' NSAID-sparing effect of glucosamine (specifically
      Structoflex(r)) in patients with knee OA compared with a control population of
      patients who did not receive a slow-acting symptomatic anti-osteoarthritis agent.
      RESEARCH DESIGN AND METHODS: This analysis was conducted over a 1-year follow-up
      period. Data were sourced from the French Disease Analyzer (IMS Lifelink EMRTM)
      database. MAIN OUTCOME MEASURES: The primary measure was the NSAID-sparing effect
      produced by Structoflex(r) compared with a matched control group. Secondary
      measures included an evaluation of the change in the number of general
      practitioner visits and use of other medicinal products related to knee OA.
      RESULTS: A total of 11,772 patients (67.66% female) were included in the analysis
      (436 and 11,336 patients in the Structoflex(r) and control groups, respectively).
      Most patients were aged 50-65 years (58.72%); 19.5% of patients were aged >76
      years. At study inclusion, 51.61% of patients had experienced OA for <1 year.
      Prior to starting Structoflex(r), 51.61% of patients had received an NSAID
      prescription. Significantly more patients who were receiving an NSAID at the time
      of starting Structoflex(r) discontinued their NSAID treatment during the follow
      up period compared with patients in the control group (32% vs 23%; p = 0.0452).
      During the 1-year follow-up period, the total mean duration of NSAID prescription
      (30.39 +/- 38.64 days vs 37.82 +/- 54.62 days; p = 0.0109) and the mean number of
      days (calculated using Defined Daily Dose) on NSAID (45.12 +/- 49.03 days vs
      53.00 +/- 71.14 days; p = 0.0333) was significantly lower in Structoflex(r)
      treated patients compared with control group patients. CONCLUSIONS: This large
      'real world' analysis demonstrated a significant NSAID-sparing effect of
      glucosamine in patients with knee OA.

PMID- 24127737
TI  - The proto-oncogene JUN is a target of the heat shock transcription factor HSF1.
AB  - The transcription factor activator protein-1 (AP-1) participates in many aspects
      of cell physiology, such as cellular proliferation, transformation, and death. AP
      1 is a dimeric complex that primarily contains Jun and Fos family members. Here,
      we report that JUN is a target of heat shock transcription factor HSF1. HSF1 is
      the master regulator of genes encoding molecular chaperones, and is involved in
      cellular processes such as the stress response, cell differentiation, aging and
      carcinogenesis. In HeLa cells, JUN transcription was rapidly induced by heat
      treatment. We found that HSF1 bound to the JUN promoter and was necessary for its
      efficient response to heat shock. In heat-shocked cells, c-Jun-mediated gene
      expression was induced slowly following accumulation of c-Jun protein. Forced
      expression of active HSF1 in cells resulted in an increase in c-Jun expression
      and activation of c-Jun target genes. These results show that HSF1 regulates JUN
      expression, thereby modulating AP-1 activity. 

PMID- 24127738
TI  - Nationwide prevalence of inflammatory bowel disease in Sweden: a population-based
      register study.
AB  - BACKGROUND: Regional studies on inflammatory bowel disease (IBD) suggest an
      increasing prevalence over time, but no nationwide estimate has been published so
      far. AIM: To estimate the IBD prevalence in 2010 in Sweden overall, by disease,
      and in specific patient segments. METHODS: Patients were identified according to
      international classification codes for ulcerative colitis and Crohn's disease in
      in-patient care (1987-2010), day surgery and nonprimary out-patient care (1997
      2010) in the nationwide Swedish Patient Register. RESULTS: Requiring two or more
      diagnoses of IBD in nonprimary care, a total of 61 344 individuals with physician
      diagnosed IBD were alive in Sweden in 2010 (mean age 50 years; 51% men),
      corresponding to a prevalence of 0.65% (95% CI, 0.65-0.66). The prevalence
      increased with age, and peaked in women at ages 50-59 years and in men at ages 60
      69 years. Adding the requirement of IBD as main (vs. main or contributory)
      diagnosis code, or diagnosis from an internal medicine/gastroenterology/surgery
      department did not change the prevalence estimate. Prevalence of actively treated
      disease (defined as two or more IBD-related visits, of which one occurred in
      2010, plus at least one dispensed prescription of IBD-related drugs in 2010) was
      0.27% (95% CI, 0.27-0.28). CONCLUSIONS: The Swedish nationwide register-based IBD
      prevalence was higher compared with previous Swedish and international estimates.
      While prevalence estimates were robust across different case definitions, once
      two or more visits were required, only about one-third of prevalent patients were
      drawing resources from specialised care in 2010.

PMID- 24127736
TI  - Long-term testosterone therapy in hypogonadal men ameliorates elements of the
      metabolic syndrome: an observational, long-term registry study.
AB  - AIM: The goal of this study was to determine if long-term testosterone (T)
      therapy in men with hypogonadism, henceforth referred to as testosterone
      deficiency (TD), ameliorates or improves metabolic syndrome (MetS) components.
      METHODS: We performed a cumulative registry study of 255 men, aged between 33 and
      69 years (mean 58.02 +/- 6.30) with subnormal plasma total T levels (mean: 9.93
      +/- 1.38; range: 5.89-12.13 nmol/l) as well as at least mild symptoms of TD
      assessed by the Aging Males' symptoms scale. All men received treatment with
      parenteral T undecanoate 1000 mg (Nebido((r)) , Bayer Pharma, Berlin, Germany),
      administered at baseline and 6 weeks and thereafter every 12 weeks for up to 60
      months. Lipids, glucose, liver enzymes and haemoglobin A1c analyses were carried
      out in a commercial laboratory. Anthropometric measurements were also made
      throughout the study period. RESULTS: Testosterone therapy restored physiological
      T levels and resulted in reductions in total cholesterol (TC) [7.29 +/- 1.03 to
      4.87 +/- 0.29 mmol/l (281.58 +/- 39.8 to 188.12 +/- 11.31 mg/dl)], low-density
      lipoprotein cholesterol [4.24 +/- 1.07 to 2.84 +/- 0.92 mmol/l (163.79 +/- 41.44
      to 109.84 +/- 35.41 mg/dl)], triglycerides [3.14 +/- 0.58 to 2.16 +/- 0.13 mmol/l
      (276.16 +/- 51.32 to 189.78 +/- 11.33 mg/dl)] and increased high-density
      lipoprotein levels [1.45 +/- 0.46 to 1.52 +/- 0.45 mmol/l (56.17 +/- 17.79 to
      58.85 +/- 17.51 mg/dl)] (p < 0.0001 for all). There were marked reductions in
      systolic and diastolic blood pressure, blood glucose, haemoglobin A1c , C
      reactive protein (6.29 +/- 7.96 to 1.03 +/- 1.87 U/l), alanine aminotransferase
      and aspartate aminotransferase (p < 0.0001 for all). CONCLUSIONS: Long-term T
      therapy, at physiological levels, ameliorates MetS components. These findings
      strongly suggest that T therapy in hypogonadal men may prove useful in reducing
      the risk of cardiometabolic diseases.

PMID- 24127739
TI  - Extracorporeal membrane oxygenation for refractory acute respiratory distress
      syndrome in severe malaria.
AB  - BACKGROUND: Severe malaria may be complicated by the acute respiratory distress
      syndrome (ARDS), which is associated with a high mortality. In the present
      report, a series of three cases of imported malaria complicated by refractory
      severe ARDS supported with extracorporeal membrane oxygenation (ECMO) is
      presented. METHODS: One female and two male adult patients (ages 39 to 53) were
      included. Two patients had Plasmodium falciparum infection and one patient had
      Plasmodium vivax and Plasmodium ovale co-infection. Anti-malarial therapy
      consisted in intravenous quinine (in two patients) and intravenous quinidine (in
      one patient), plus clindamycin or doxycycline. RESULTS: Despite lung protective
      ventilation, a conservative strategy of fluid management, corticosteroids (two
      patients), prone position (two patients) and inhaled nitric oxide (one patient),
      refractory severe ARDS supervened (PaO2 to FiO2 ratio 68) and venovenous ECMO was
      then initiated. In one patient, a bicaval dual-lumen cannula was inserted; in the
      two other patients, a two-site configuration was used. Two patients survived to
      hospital-discharge (duration of ECMO support: 8.5 days) and one patient died from
      nosocomial sepsis and multi-organ failure after 40 days of ECMO support.
      CONCLUSIONS: ECMO support allowed adequate oxygenation and correction of
      hypercapnia under lung protective ventilation, therefore reducing ventilator
      induced lung injury. ECMO referral should be considered early in malaria
      complicated by severe ARDS refractory to conventional treatment.

PMID- 24127741
TI  - Substituent effects on energetics of peptide-carboxylate hydrogen bonds as
      studied by 1H NMR spectroscopy: implications for enzyme catalysis.
AB  - Substituent effects in N-H...O hydrogen bonds were estimated by comparing the
      acidities of two series of model compounds: N-benzoylanthranilic acids (A) and 4
      benzoylamidobenzoic acids (B). Intramolecular N-H...O hydrogen bonds were found
      to be present in the A series of compounds, while B acids were used as control
      models. The respective pK(a) values for A and B acids were determined
      experimentally in DMSO solution using proton NMR spectroscopy. With X = H, the
      pK(a) for A and B acids were observed to be 7.6 and 11.6, respectively, a
      difference of 4.0 units (DeltapK(a)). However, with X = p-NO2, the DeltapK(a)
      value between A and B acids increased to 4.7 units: the pK(a) values for A and B
      acids were determined as 6.7 and 11.4, respectively. The DeltapK(a) values
      between A and B acids as a function of the X substituents were studied in 10
      other examples. The effects of X substituents in A acids could be predicted on
      the basis of the observed linear Hammett correlations, and the sensitivity of
      each substituent effect was found to be comparable to those observed for the
      ionization of substituted benzoic acids (rho = 1.04 for A acids, and rho = 1.00
      for benzoic acids).

PMID- 24127740
TI  - Ellagic acid and embelin affect key cellular components of pancreatic
      adenocarcinoma, cancer, and stellate cells.
AB  - Ellagic acid is a polyphenolic phytochemical present in many fruits and nuts with
      anticancer properties demonstrated in experimental tumor studies. Embelin is a
      benzoquinone phytochemical isolated from the Japanese herb Ardisiae Japonicae and
      has been shown to induce apoptosis in cancer cells. We found that ellagic acid
      and embelin each dose-dependently increased apoptosis and inhibited proliferation
      in human pancreatic cancer cells, MIA PaCa-2 and HPAF-II cells, and in pancreatic
      stellate cells, which are progenitors of pancreatic cancer desmoplasia. In each
      of these cell types, combinations of ellagic acid and embelin at low micromolar
      concentrations (0.5-3 MUM) induced synergistic increases in apoptosis and
      decreases in proliferation. Ellagic acid decreased NF-kappaB transcriptional
      activity, whereas embelin decreased STAT-3 phosphorylation and protein expression
      of its downstream target survivin in cancer cells. In vivo dietary ellagic acid
      alone or in combination with embelin decreased tumor size and tumor cellularity
      in a subcutaneous xenograft mouse model of pancreatic cancer. These results show
      that ellagic acid and embelin interact with divergent intracellular signaling
      pathways resulting in augmentation of apoptosis and inhibition of proliferation
      at low micromolar concentrations for the key cellular components of pancreatic
      adenocarcinoma.

PMID- 24127742
TI  - CT perfusion mismatch in subacute stroke: oligemia or luxury perfusion? Response
      to persistent benign oligemia causes ct perfusion mismatch in patients with
      intracranial large artery occlusive disease during subacute stroke.

PMID- 24127743
TI  - Measuring the unmet supportive care needs of cancer support persons: the
      development of the support person's unmet needs survey--short form.
AB  - Few rigorous measures of unmet needs have been developed for cancer support
      persons. This study describes the development of a short version of the Support
      Person's Unmet Needs Survey (SPUNS). Cancer survivors [n = 1589, 612 (52%) men,
      mean age of 62.5 years, SD 11.5] 1-5 years post diagnosis and recruited through
      three Canadian population-based cancer registries were asked to pass a survey
      package on to their principal support person. Surveys were returned by 1183
      support persons. The survey included the long form of the SPUNS, which contains
      78 items. Fifty-two items were deleted using a combination of expert opinion and
      statistical criteria. Analysis of the remaining items revealed a five-factor
      structure. The original factors were retained with the exception of a merging of
      the personal and emotional needs subscales. Cronbach's alpha co-efficients for
      all subscales were >= 0.87, and intraclass correlation of domain scores of the
      short and long versions of the SPUNS were high. The SPUNS short form was able to
      discriminate between support persons of survivors who had (n = 147), and those
      who had not received treatment in the past month (n = 969). At just 26 items, it
      is likely to have strong clinical and research applicability.

PMID- 24127744
TI  - Pustulotic arthro-osteitis associated with palmoplantar pustulosis.
AB  - Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by
      sterile pustules predominantly involving the palms and soles of middle-aged
      women. PPP frequently develops or exacerbates following focal infections, such as
      tonsillitis, odontogenic infection and sinusitis, either with or without
      arthralgia and/or extra-palmoplantar lesions. Pustulotic arthro-osteitis (PAO) is
      a joint comorbidity of PPP, most often affecting the anterior chest wall. PAO is
      sometimes regarded as the same entity as synovitis, acne, pustulosis,
      hyperostosis and osteitis (SAPHO) syndrome, and may be a subtype or incomplete
      type of SAPHO syndrome; however, there are several differences. In Japanese
      patients, PPP with PAO is frequently seen, whereas SAPHO syndrome in the true
      meaning is rare. A difference of incidence depending on race suggests that
      different genetic backgrounds may be responsible for susceptibility to these
      disorders. Bacterial infection, especially Propionibacterium acnes, is suggested
      to play an important role in the pathogenesis of SAPHO syndrome. P. acnes is
      responsible for acne, however, bacterium is unassociated with PPP skin lesions
      which are characterized by sterile pustules. On the other hand, PAO is frequently
      triggered by focal infection, and treatment of focal infection results in
      dramatic effects on the release of joint pain. This paper reviews current
      insights into the clinicopathophysiology of PAO, and discusses its possible
      mechanisms in comparison with SAPHO syndrome.

PMID- 24127745
TI  - Hybrid of Co(3)Sn(2)@Co nanoparticles and nitrogen-doped graphene as a lithium
      ion battery anode.
AB  - A facile strategy was designed for the fabrication of hybrid of Co3Sn2@Co
      nanoparticles (NPs) and nitrogen-doped graphene (NG) sheets through a
      hydrothermal synthesis, followed by annealing process. Core-shell architecture of
      Co3Sn2@Co pin on NG is designed for the dual encapsulation of Co3Sn2 with
      adaptable ensembles of Co and NG to address the structural and interfacial
      stability concerns facing tin-based anodes. In the resulted unique architecture
      of Co3Sn2@Co-NG hybrid, the sealed cobalt cover prevents the direct exposer of Sn
      with electrolyte because of encapsulated structure and keeps the structural and
      interfacial integrity of Co3Sn2. However, the elastically strong, flexible and
      conductive NG overcoat accommodates the volume changes and therefore brings the
      structural and electrical stabilization of Co3Sn2@Co NPs. As a result, Co3Sn2@Co
      NG hybrid exhibits extraordinary reversible capacity of 1615 mAh/g at 250 mA/g
      after 100 cycles with excellent capacity retention of 102%. The hybrid bears
      superior rate capability with reversible capacity of 793.9 mAh/g at 2500 mA/g and
      Coulombic efficiency nearly 100%. 

PMID- 24127746
TI  - The interactive roles of zinc and calcium in mitochondrial dysfunction and
      neurodegeneration.
AB  - Zinc has been implicated in neurodegeneration following ischemia. In analogy with
      calcium, zinc has been proposed to induce toxicity via mitochondrial dysfunction,
      but the relative role of each cation in mitochondrial damage remains unclear.
      Here, we report that under conditions mimicking ischemia in hippocampal neurons -
      normal (2 mM) calcium plus elevated (> 100 MUM) exogenous zinc - mitochondrial
      dysfunction evoked by glutamate, kainate or direct depolarization is, despite
      significant zinc uptake, primarily governed by calcium. Thus, robust
      mitochondrial ion accumulation, swelling, depolarization, and reactive oxygen
      species generation were only observed after toxic stimulation in calcium
      containing media. This contrasts with the lack of any mitochondrial response in
      zinc-containing but calcium-free medium, even though zinc uptake and toxicity
      were strong under these conditions. Indeed, abnormally high, ionophore-induced
      zinc uptake was necessary to elicit any mitochondrial depolarization. In calcium-
      and zinc-containing media, depolarization-induced zinc uptake facilitated cell
      death and enhanced accumulation of mitochondrial calcium, which localized to
      characteristic matrix precipitates. Some of these contained detectable amounts of
      zinc. Together these data indicate that zinc uptake is generally insufficient to
      trigger mitochondrial dysfunction, so that mechanism(s) of zinc toxicity must be
      different from that of calcium.

PMID- 24127747
TI  - Electrospun blends of gelatin and gelatin-dendrimer conjugates as a wound
      dressing and drug-delivery platform.
AB  - In this work, we report a new nanofiber construct based on electrospun blends of
      gelatin and gelatin-dendrimer conjugates. Highly branched star-shaped
      polyamidoamine (PAMAM) dendrimer G3.5 was covalently conjugated to gelatin via
      EDC/NHS chemistry. Blends of gelatin and gelatin-dendrimer conjugates mixed with
      various loading levels of silver acetate (0, 0.83, 1.65, and 3.30% w/w) were
      successfully electrospun into nanofiber constructs (NCs). The NCs were further
      converted into semi-interpenetrating networks (sIPNs) with photoreactive
      polyethylene glycol diacrylate (Mn = 575 g mol(-1)) (PEG DA575). They were
      characterized in terms of fiber morphology, diameter, pore size, permeability,
      degradation, and mechanical properties. The resulting sIPN NCs retained nanofiber
      morphology, possessed similar fiber diameters to counterpart NCs, and gained
      improved structural stability. The sIPN NCs also showed good swelling capacity
      owing to porous structures and were permeable to aqueous solutions. Silver
      containing sIPN NCs allowed sustained silver release and showed antimicrobial
      activity against two common types of pathogens, Staphylococcus aureus and
      Pseudomonas aeruginosa. Incorporation of dendrimers into the gelatin nanofibers
      through covalent conjugation not only expands drug loading capacity of nanofiber
      constructs but also provides tremendous flexibility for developing
      multifunctional electrospun dressing materials. 

PMID- 24127748
TI  - A nanosensor for ultrasensitive detection of oversulfated chondroitin sulfate
      contaminant in heparin.
AB  - Heparin has been extensively used as an anticoagulant for the last eight decades.
      Recently, the administration of a contaminated batch of heparin caused 149 deaths
      in several countries including USA, Germany, and Japan. The contaminant
      responsible for the adverse effects was identified as oversulfated chondroitin
      sulfate (OSCS). Here, we report a rapid, ultrasensitive method of detecting OSCS
      in heparin using a nanometal surface energy transfer (NSET) based gold-heparin
      dye nanosensor. The sensor is an excellent substrate for heparitinase enzyme, as
      evidenced by ~70% recovery of fluorescence from the dye upon heparitinase
      treatment. However, the presence of OSCS results in diminished fluorescence
      recovery from the nanosensor upon heparitinase treatment, as the enzyme is
      inhibited by the contaminant. The newly designed nanosensor can detect as low as
      1 * 10(-9) % (w/w) OSCS making it the most sensitive tool to date for the
      detection of trace amounts of OSCS in pharmaceutical heparins.

PMID- 24127749
TI  - Frequency of the off-label use of monoclonal antibodies in clinical practice: a
      systematic review of the literature.
AB  - BACKGROUND: The monoclonal antibodies represent novel therapeutic options for
      many clinical entities. This study aimed to study the frequency of the off-label
      use to total use of different monoclonal antibodies in clinical practice.
      METHODS: This study systematically searched the PubMed and Scopus databases for
      relevant studies. RESULTS: Fifteen studies were considered eligible for inclusion
      in this review. Eight of the included studies referred to the off-label use of
      anti-neoplastic monoclonal antibodies, three referred to immunosuppressive ones,
      and four to other types of monoclonal antibodies. The most studied anti
      neoplastic monoclonal antibody was rituximab; which was prescribed off-label at a
      frequency varying between 16-75%, mostly for an unapproved diagnosis. Bevacizumab
      was prescribed off-label for age-related macular degeneration more often than
      ranibizumab, the approved monoclonal antibody for this condition. Of the
      immunosuppressive monoclonal antibodies, infliximab was used off-label in an
      average of 15.4% (range=2.8-25%) and adalimumab in 10.5% (range=0-15.4% in
      different years). CONCLUSION: The frequency of off-label use of different types
      of monoclonal antibodies varies, but appears to be considerably high for specific
      monoclonal antibodies or indications. In certain examples, this might reflect
      implementation into clinical practice of relevant scientific data, albeit not of
      the strength or quality that suffices for receipt of regulatory approval. In
      others, it might relate to the sub-optimal effectiveness and considerable
      toxicity of the conventional therapies. Still, the clinician should bear in mind
      the potential costs and toxicity that can be associated with off-label use of
      monoclonal antibodies.

PMID- 24127751
TI  - Is the detection of circulating tumor cells in locally advanced pancreatic cancer
      a useful prognostic marker?
AB  - Evaluation of: Bidard FC, Huguet F, Louvet C et al. Circulating tumor cells in
      locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the
      LAP 07 trial. Ann. Oncol. 24(8), 2057-2061 (2013). Circulating tumor cells (CTCs)
      may be shed from the primary tumor and lead to metastatic disease. This evaluated
      article reports on CTCs in locally advanced pancreatic cancer (LAPC). By
      assessing CTCs from peripheral blood prior to any treatment and after 2 months of
      chemotherapy, 11% of patients had detectable CTCs. These patients had a poorer
      overall survival. With such low numbers of CTCs detected in LAPC patients, it is
      unclear whether CTCs can actually contribute toward tumor invasiveness and spread
      in such an aggressive cancer. Although this is a well-designed study, the small
      number of patients with detectable CTCs means that the statistical power is not
      great enough to make firm conclusions. Therefore, this expensive assay needs
      further investigation before being used a prognostic marker in patients with
      LAPC. 

PMID- 24127750
TI  - Volatiles produced by soil-borne endophytic bacteria increase plant pathogen
      resistance and affect tritrophic interactions.
AB  - Volatile organic compounds (VOCs) released by soil microorganisms influence plant
      growth and pathogen resistance. Yet, very little is known about their influence
      on herbivores and higher trophic levels. We studied the origin and role of a
      major bacterial VOC, 2,3-butanediol (2,3-BD), on plant growth, pathogen and
      herbivore resistance, and the attraction of natural enemies in maize. One of the
      major contributors to 2,3-BD in the headspace of soil-grown maize seedlings was
      identified as Enterobacter aerogenes, an endophytic bacterium that colonizes the
      plants. The production of 2,3-BD by E. aerogenes rendered maize plants more
      resistant against the Northern corn leaf blight fungus Setosphaeria turcica. On
      the contrary, E. aerogenes-inoculated plants were less resistant against the
      caterpillar Spodoptera littoralis. The effect of 2,3-BD on the attraction of the
      parasitoid Cotesia marginiventris was more variable: 2,3-BD application to the
      headspace of the plants had no effect on the parasitoids, but application to the
      soil increased parasitoid attraction. Furthermore, inoculation of seeds with E.
      aerogenes decreased plant attractiveness, whereas inoculation of soil with a
      total extract of soil microbes increased parasitoid attraction, suggesting that
      the effect of 2,3-BD on the parasitoid is indirect and depends on the composition
      of the microbial community.

PMID- 24127752
TI  - On-chip evaluation of neutrophil activation and neutrophil-endothelial cell
      interaction during neutrophil chemotaxis.
AB  - Neutrophils are always surrounded by/interacting with other components of the
      immune system; however, the current mechanistic understanding of neutrophil
      function is largely based on how neutrophils respond to a single chemical signal
      in a simplified environment. Such approaches are unable to recapitulate the in
      vivo microenvironment; thus, cell behavior may not fully represent the
      physiological behavior. Herein, we exploit a microfluidic model of the complex in
      vivo milieu to investigate how cell-cell interactions influence human neutrophil
      migration and surface marker expression. Neutrophil migration against a
      bacterially derived chemoattractant (formyl-met-leu-phe, fMLP), with and without
      preactivation by interleukins (interleukin-2 or interleukin-6), was evaluated in
      the presence and absence of endothelial support cells. Preactivation by
      interleukins or interaction with endothelial cells resulted in altered migration
      rates compared to naive neutrophils, and migration trajectories deviated from the
      expected movement toward the fMLP signal. Interestingly, interaction with both
      interleukins and endothelial cells simultaneously resulted in a slight
      compensation in the deviation-on endothelial cells, 34.4% of untreated
      neutrophils moved away from the fMLP signal, while only 15.2 or 22.2%
      (interleukin-2-or interleukin-6-activated) of preactivated cells moved away from
      fMLP. Neutrophils interacting with interleukins and/or endothelial cells were
      still capable of prioritizing the fMLP signal over a competing chemoattractant,
      leukotriene B4 (LTB4). Fluorescence imaging of individual human neutrophils
      revealed that neutrophils treated with endothelial-cell-conditioned media showed
      up-regulation of the surface adhesion molecules cluster determinant 11b and 66b
      (CD11b and CD66b) upon stimulation. On the other hand, CD11b and CD66b down
      regulation was observed in untreated neutrophils. These results leverage single
      cell analysis to reveal that the interaction between neutrophils and endothelial
      cells is involved in surface marker regulation and thus chemotaxis of
      neutrophils. This study brings new knowledge about neutrophil chemotaxis in the
      context of cell-to-cell communications, yielding both fundamental and
      therapeutically relevant insight.

PMID- 24127753
TI  - The interleukin-6-type cytokine oncostatin M induces aryl hydrocarbon receptor
      expression in a STAT3-dependent manner in human HepG2 hepatoma cells.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor
      that mediates the toxicity of dioxins, polycyclic aromatic hydrocarbons and
      related environmental pollutants. Besides drug metabolism, several studies have
      provided evidence that the AHR and its downstream targets trigger important
      developmental, physiological and pathophysiological processes. However, in
      contrast to the molecular mechanisms of AHR-dependent signaling pathways, the
      transcriptional regulation of the AHR gene itself is as yet only marginally
      understood. We found that the pleiotropic interleukin (IL)-6-type cytokine
      oncostatin M (OSM) is an inducer of AHR mRNA and protein expression in human
      HepG2 hepatocarcinoma cells. Analyses of the human AHR promoter revealed the
      existence of a putative signal transducer and activator of transcription (STAT)
      binding element 5'-upstream of the transcription start site. By means of site
      directed mutagenesis, inhibitor experiments and electrophoretic mobility shift
      assays, we demonstrated that this STAT motif is recognized by STAT3 to regulate
      basal and cytokine-inducible AHR expression in HepG2 cells. The identification of
      the AHR as a downstream target of IL-6-type cytokine-stimulated STAT3 signaling
      may contribute to a better understanding of the multiple facets of AHR during
      development, physiology and disease. 

PMID- 24127754
TI  - Ultrafast nonlinear control of progressively loaded, single plasmonic
      nanoantennas fabricated using helium ion milling.
AB  - We demonstrate milling of partial antenna gaps and narrow conducting bridges with
      nanometer precision using a helium ion beam microscope. Single particle
      spectroscopy shows large shifts in the plasmonic mode spectrum of the milled
      antennas, associated with the transition from capacitive to conductive gap
      loading. A conducting bridge of nanometer height is found sufficient to shift the
      antenna from the capacitive to the conductive coupling regime, in agreement with
      circuit theory. Picosecond pump-probe spectroscopy reveals an enhanced nonlinear
      response for partially milled antennas, reaching an optimum value for an
      intermediate bridge height. Our results show that manipulation of the antenna
      load can be used to increase the nonlinear response of plasmonic antennas. 

PMID- 24127755
TI  - Primary esophageal adenosquamous carcinoma: a retrospective analysis of 24 cases.
AB  - Primary adenosquamous carcinoma (ASC) of the esophagus is a rare kind of
      malignancy characterized by mixed glandular and squamous differentiation as well
      as a propensity for aggressive clinical behavior. Data on the evaluation of the
      clinicopathological features and the prognosis of patients suffering from this
      malignancy are few because of the rarity of this disease. We conducted a
      retrospective review of 24 patients with primary esophageal ASC among 6546
      esophageal cancer patients who underwent transthoracic esophagectomy in our
      hospital. The clinicopathological presentation, diagnosis, treatment, and
      prognostic factors of the patients were respectively investigated. The Kaplan
      Meier method and the log rank test were used to calculate and compare overall
      survival (OS). The Cox proportional hazards model was employed to identify
      independent prognostic factors. There were 18 males and 6 females with a median
      age of 60 years (range: 40-78 years). The clinical symptoms, macroscopic type, as
      well as the radiological and endoscopic features of esophageal ASC were similar
      to those of esophageal squamous cell carcinoma. Sixteen (88.9%) of the 18 cases
      who underwent preoperative esophagoscopic biopsy were misdiagnosed as
      adenocarcinoma or squamous cell carcinoma. The overall median follow-up period
      was 36 months, and the median survival time was 32 months. The 1, 3, 5-year OS
      rates were 75.0%, 48.5%, and 19.4%, respectively. Univariate analysis showed that
      gender (P=0.047), lymph node metastasis (P=0.007), and TNM stage (P=0.037) were
      important factors associated with OS of the 22 patients who underwent radical
      resection. Multivariate analysis showed that the pathological N stage was the
      only independent prognostic factor (P=0.031, hazard ratio [HR], 5.369, 95%
      confidence interval [CI], 1.167-24.700). These results suggest that esophageal
      ASC is an uncommon disease prone to be misdiagnosed by endoscopic biopsy.
      Surgical resection is the primary treatment, but the prognosis of ASC is usually
      poorer than conventional squamous cell carcinoma. Lymph node metastasis is an
      independent prognostic factor after radical resection.

PMID- 24127756
TI  - The national employment guarantee scheme and inequities in household spending on
      food and non-food determinants of health in rural India.
AB  - INTRODUCTION: Inequities in a population in spending on food and non-food items
      can contribute to disparities in health status. The Mahatma Gandhi National Rural
      Employment Guarantee Scheme (MGNREGS) was launched in rural India in 2006, aimed
      at providing at least 100 days of manual work to a member in needy households.
      METHODS: We used nationally representative data from the consumer expenditure
      surveys of 2004-05 and 2009-10 and the employment survey of 2009-10 conducted by
      National Sample Survey Organisation to assess the effect of MGNREGS in reducing
      inequities in consumption of food and non-food items between poor and non-poor
      households in the states of India. Variations among the states in implementation
      of MGNREGS were examined using the employment and unemployment survey data, and
      compared with official programme data up to 2012-13. Inequity in spending on food
      and non-food items was assessed using the ratio of monthly per capita consumer
      expenditure (MPCE) between the most vulnerable (labourer) and least vulnerable
      categories of households. RESULTS: The survey data suggested 1.42 billion person
      days of MGNRGES employment in the 2009-10 financial year, whereas the official
      programme data reported 2.84 billion person-days. According to the official data,
      the person-days of MGNRGES employment decreased by 43.3% from 2009-10 to 2012-13
      for the 9 large less developed states of India. Survey data revealed that the
      average number of MGNREGS work days in a year per household varied from 42 days
      in Rajasthan to less than 10 days in 14 of the 20 major states in India in 2009
      10. Rajasthan with the highest implementation of MGNRGES among the 9 less
      developed states of India had the highest relative decline of 10.4% in the food
      spending inequity from 2004-05 to 2009-10 between the most vulnerable and less
      vulnerable households. The changes in inequity for non-food spending did not have
      any particular pattern across the less developed states. In the most vulnerable
      category, the households in Rajasthan that got 100 or more days of work in a year
      under MGNREGS had a 25.9% increase in MPCE. CONCLUSION: MGNREGS seems to have
      contributed to the reduction in food consumption inequity in rural Rajasthan in
      2009-10, and has the potential of making a similar contribution with higher level
      of implementation of this programme in other states. Non-food consumption
      inequities benefited less from MGNRGES until 2009-10. The reported decrease in
      the MGNRGES employment person-days in the less developed states of India from
      2009-10 to 2012-13 is of concern.

PMID- 24127757
TI  - Effects of dexmedetomidine and xylazine on cardiovascular function during total
      intravenous anaesthesia with midazolam and ketamine and recovery quality and
      duration in horses.
AB  - OBJECTIVES: To compare cardiovascular effects and recovery quality and duration
      of total intravenous anaesthesia (TIVA) with xylazine-ketamine-midazolam or
      dexmedetomidine-ketamine-midazolam. STUDY DESIGN: Prospective, randomized
      experimental cross-over trial. ANIMALS: Eight adult warmblood horses. METHODS:
      After sedation with acepromazine and either xylazine [0.5 mg kg(-1) ,
      intravenously (IV)] or dexmedetomidine (3.5 MUg kg(-1) IV) anaesthesia was
      induced with ketamine and midazolam and maintained with a constant rate infusion
      (CRI) of xylazine (1 mg kg(-1)  hour(-1) ) [XKM] or dexmedetomidine (7 MUg kg(-1)
      hour(-1) ) [DKM] in combination with midazolam (0.1 mg kg(-1)  hour(-1) ), and
      ketamine infusion (initially 3 mg kg(-1)  hour(-1) ) for 120 minutes. Ketamine
      infusion rate was increased in response to positive reactions to electrical
      nociceptive stimulation performed every 30 minutes. Heart rate (HR), mean
      arterial blood pressure (MAP) and cardiac output (Qt) were measured before
      treatment (baseline), after sedation (not Qt), and during anaesthesia. Xylazine,
      dexmedetomidine, midazolam and ketamine kinetics were calculated, from plasma
      drug concentrations. Twenty minutes after end of TIVA, flumazenil (0.01 mg kg(-1)
      IV) was administered. Recovery quality and duration were assessed. Two-way
      analysis of variance with repeated measurements or Wilcoxon signed rank test as
      relevant were used to analyse data with an alpha of 5%. RESULTS: Compared to
      baseline, MAP did not change, while similar, but limited, decreases in HR and Qt
      were observed in both TIVA's. Mean ketamine doses of 3.7 mg kg(-1)  hour(-1) were
      required with both treatments. Plasma concentrations of dexmedetomidine and
      xylazine showed high intra- and inter-individual changes with elimination half
      lifes of 46 +/- 7 minutes and 64 +/- 13 minutes, respectively. Recovery quality
      was good to excellent with mean duration of 37 +/- 16 and 46 +/- 21 minutes after
      stopping TIVA with XKM and DKM, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      Both drug combinations are suitable to maintain anaesthesia for two hours, with
      good cardiovascular and good to excellent recovery conditions.

PMID- 24127758
TI  - Visual disorders in children with cerebral palsy: is the picture still 'blurred'?

PMID- 24127759
TI  - The creation of virtual teeth with and without tooth pathology for a virtual
      learning environment in dental education.
AB  - PURPOSE: To describe the development and opportunities for implementation of
      virtual teeth with and without pathology for use in a virtual learning
      environment in dental education. MATERIAL AND METHODS: The creation of virtual
      teeth begins by scanning a tooth with a cone beam CT. The resulting scan consists
      of multiple two-dimensional grey-scale images. The specially designed software
      program ColorMapEditor connects these two-dimensional images to create a three
      dimensional tooth. With this software, any aspect of the tooth can be modified,
      including its colour, volume, shape and density, resulting in the creation of
      virtual teeth of any type. RESULTS: This article provides examples of realistic
      virtual teeth with and without pathology that can be used for dental education.
      ColorMapEditor offers infinite possibilities to adjust and add options for the
      optimisation of virtual teeth. DISCUSSION: Virtual teeth have unlimited
      availability for dental students, allowing them to practise as often as required.
      Virtual teeth can be made and adjusted to any shape with any type of pathology.
      Further developments in software and hardware technology are necessary to refine
      the ability to colour and shape the interior of the pulp chamber and surface of
      the tooth to enable not only treatment but also diagnostics and thus create a
      greater degree of realism. CONCLUSION: The creation and use of virtual teeth in
      dental education appears to be feasible but is still in development; it offers
      many opportunities for the creation of teeth with various pathologies, although
      an evaluation of its use in dental education is still required.

PMID- 24127760
TI  - Failing to fail: clinicians' experience of assessing underperforming dental
      students.
AB  - INTRODUCTION: Anecdotal evidence within a UK dental school indicated that staff's
      grading did not always match their evaluation of students' clinical proficiency.
      The invalid assessment of underperforming students, which has considerable
      ramifications, has been reported internationally for students of nursing and
      medicine, but a database search revealed no accounts for dental education. AIM:
      To develop an understanding of clinicians' approaches to assessing
      underperforming dental students. METHODOLOGY: Seventeen clinical staff were
      interviewed (eleven females, six males). Interviews were recorded and transcribed
      verbatim. A grounded theory methodology was used, with simultaneous data
      collection and analysis. The main analytical technique was constant comparison.
      FINDINGS: Participants' shared basic problem was Assessing undergraduate
      students, expressed as how they evaluated and used the assessment system or
      perceived others to do so. The core category, which explains what clinical staff
      do to manage their difficulties with assessment, was identified as Failing to
      Fail and has three subcategories: Evaluating the Assessment System, Shielding the
      Student and Protecting Myself. CONCLUSION: This study has substantiated the
      complexity of failing to fail and confirmed that some causes are shared across
      healthcare professions, although insufficient staff discussion, the avoidance of
      confrontation and the impact of negative student attitude are not reported
      elsewhere or are minor findings. It is recommended that clinical staff receive
      additional training in assessment and that they are made more aware of their
      learning needs, their attitudes and beliefs. Increased discussion between staff
      about assessment and about students known to be in difficulty is essential.

PMID- 24127761
TI  - Psychometric properties of the Greek version of the Toronto Composite Empathy
      Scale in Greek dental students.
AB  - INTRODUCTION: Empathy levels of health practitioners are related to patient
      satisfaction and treatment outcomes. The Toronto Composite Empathy Scale (TCES)
      was recently developed to assess cognitive and emotional empathy levels in both
      professional and personal spheres, and tested in an English-speaking sample of
      dental students. The aim of this study was to examine the psychometrics of the
      Greek version of the TCES. MATERIALS AND METHODS: The TCES was translated into
      Greek and administered to all of the dental students at Aristotle University of
      Thessaloniki. A random subset of students completed the questionnaire twice for
      test-retest analysis. RESULTS: Nearly all (96.5%) of the students completed the
      questionnaire. The internal consistencies of each of the four subscales were
      generally acceptable (Cronbach's alphas: 0.676-0.805), and the scale showed good
      discriminant and convergent validities (r's for discriminant validity: 0.217 and
      0.103; r's for convergent validity: 0.595 and 0.700). Test-retest reliabilities
      ranged from 0.478 to 0.779. After eliminating items that fell on both cognitive
      and emotional factors, a rotated factor analysis indicated that the items loaded
      on two cognitive and three emotional factors. DISCUSSION: Our results indicate
      that the Greek version of the TCES has good psychometric properties. The factor
      analysis indicates that the emotional and cognitive aspects of empathy are
      distinct, supporting the need to address both aspects in studies of empathy.
      CONCLUSIONS: The Greek version of the TCES is a reliable and valid tool for the
      measurement of cognitive and emotional empathy, in both professional and personal
      life, in Greek dental students.

PMID- 24127762
TI  - Medical students' child oral-health-related knowledge, practices and attitudes.
AB  - OBJECTIVE: This study evaluated medical interns' oral health knowledge, and other
      factors influencing their ability and willingness to perform oral-health-related
      practices for high-caries-risk children. METHODS: A 15-item survey was emailed to
      all eligible graduating fifth-year medical students at King Khalid University
      Hospital to address these areas of interest. Chi-square statistics and logistic
      regression models were used to analyse data. RESULTS: One-hundred and twenty-one
      (49%) usable surveys were returned from two mailings. On questions regarding
      comfort levels when performing oral-health-related practices on children under
      age 3, physicians noted high levels of comfort with all specified oral health
      practices. Regarding satisfaction of students with medical training, the majority
      of respondents (87.5%) rated their medical training as fair or poor in preparing
      them for oral health assessments compared to only 35%, 29% and 7% of respondents
      giving fair or poor ratings to child abuse identification, caring for special
      needs patients and primary care paediatric practice, respectively. Additionally,
      although 90% of respondents noted that the role of primary physicians in
      counselling/referring children with oral health was important, 60% did not agree
      with the AAPD and AAP guidelines that state that all children should be referred
      to a dentist by 12 months of age. Multivariate logistic regression analyses
      revealed several statistically significant variables that predict the likelihood
      of performing various oral-health-related practices. The choice of public-health
      oriented future clinical goals, the level of oral health knowledge, how interns
      rated their oral health training in medical school and the average number of
      children seen per week, all--to varying degrees--proved important predicator
      variables for the likelihood of performing them once in practice. CONCLUSIONS:
      More oral-health-related training of medical students seems warranted and could
      improve their interest in providing oral-health-related screening and referrals
      in practice. Increasing student exposure to child patients and increasing
      exposures to oral health knowledge and problems could be targeted towards
      students interested in primary care and public health to use resources most
      efficiently in the effort to combat the growing caries levels amongst young
      children in Saudi Arabia.

PMID- 24127763
TI  - Practising case-based learning in oral medicine for dental students in China.
AB  - INTRODUCTION: Teacher-centred education dominates dental education in China.
      Student-centred education has recently been introduced in the School of
      Stomatology, Wuhan University, and the effectiveness of such methods needs to be
      tested. The purpose of this study is to compare the learning outcomes of case
      based learning (CBL) and lecture-based education (LBE) in an oral medicine
      curriculum. MATERIALS AND METHODS: We chose oral leukoplakia as the learning
      subject for dental students. Forty fourth-year dental students participated in
      the study. First, they were presented to basic knowledge of oral leukoplakia and
      related oral mucosal diseases. Then, they were divided into a CBL group (n=20)
      and an LBE group (n=20) by random numbers. The groups experienced the remaining
      course in separate groups. All students answered a questionnaire on their
      satisfaction with the education and the same standardised written test to analyse
      their learning outcomes. RESULTS: Both CBL and LBE courses were well accepted by
      students according to the satisfactory scores of the questionnaire. The test
      scores of the CBL group (90.00+/-6.69) were significantly higher (P<0.01) than
      those of the LBE group (83.00+/-6.77). The percentage of high test score (test
      score>=85) of the CBL group (85%) was also significantly higher (P<0.01) than
      that of the LBE group (45%). CONCLUSIONS: In this example, CBL was found to be
      more effective than LBE to teach dental students. These findings suggest that CBL
      should be added in our future oral medicine curriculum for dental students.

PMID- 24127764
TI  - The influence of a clinical rural placement programme on the work location of new
      dental graduates from the University of Sydney, NSW, Australia.
AB  - INTRODUCTION: In Australia, as in many other countries there is a disparity in
      the number of dentists working in rural locations compared with metropolitan
      areas, and this is a growing problem. The aim of the research was to monitor the
      location of recent graduates who undertook a rural clinical placement whilst in
      the final year of Sydney Dental School, to determine whether it influenced their
      choice of job location. MATERIALS AND METHODS: Students who graduated in 2008 and
      2009 were followed up to ascertain their working location. Forty per cent of the
      2009 graduates participated in a rural placement during their undergraduate
      degree and 60% did not. In 2008, none of the students went on a rural placement
      as the scheme had not been implemented. The Australian Health Practitioner
      Regulation Agency (AHPRA) internet website was used to find the working location
      of the graduates. The rural, remote and metropolitan areas (RRMA) classification
      system was used to classify which areas of Australia were metropolitan, regional,
      rural and remote zones. RESULTS: The graduates of 2008 and 2009 were followed up
      in 2011 and 2012 to ascertain their working location. In 2011, 12.7% of the 2008
      graduates were employed in a rural location compared to 27.6% of the entire 2009
      graduating class. In 2011, of those 2009 graduates who participated in the rural
      placement programme, 44.8% were working in a rural or remote region compared to
      17% of the graduates who did not participate. In 2012, the second follow-up found
      that 18.6% of the 2008 graduates were working in a rural location compared to
      25.9% of all the 2009 graduates. In 2012, 43.3% of the 2009 rural placement
      participants were found to be working in a rural location compared to 14.9% of
      the non-participants. CONCLUSIONS: The study followed up recent dental graduates'
      working locations to provide longitudinal evidence of the influence of an
      undergraduate rural placement programme on their work choices. It was found that
      a higher proportion of graduates who participated in the rural placement
      programme were working in a rural location when compared with those who had not
      been offered a placement.

PMID- 24127765
TI  - Reflective folios for dental hygiene students: what do they tell us about a
      residential aged care student placement experience?
AB  - INTRODUCTION: Community-based education programmes provide students with an
      experiential learning opportunity in a real-life context. The purpose of this
      study was to examine reflective journals to identify students' experiences and
      perceived learning during a 12-week placement programme in residential aged care
      facilities (RACF) on the NSW Central Coast, Australia. METHODOLOGY: All final
      year dental hygiene students from the University of Newcastle, Australia attended
      an aged care orientation workshop prior to commencing the RACF student placement
      programme. Throughout the placement, students were asked to record their
      educational experiences in reflective journals. Student reflections were based on
      the 'Gibbs Reflective Cycle', diarising experiences and feelings. Qualitative
      data was analysed using the constant comparative method and unitised to identify
      emergent themes. RESULTS: Sixty-seven students completed reflective journals
      during the placement programme; emergent themes indicated students felt ill
      prepared for the placement programme despite attending the orientation workshop.
      They were apprehensive and nervous prior to commencement of the placement. The
      general consensus after week 6 was that the placement became a more positive
      experience where students began to feel comfortable in the RACF environment and
      residents, and staff started to respond more positively to their presence.
      Overall, they thought the placement was challenging and confronting, but had
      improved their skills and knowledge in care of older people and increased their
      confidence in working with other healthcare professionals. CONCLUSION: The
      reflective journals provided students with the opportunity to record and reflect
      on their experience and perceived learning during the placement programme.
      Student reflections identified negative experiences at the commencement of the
      placement, suggesting a need for additional orientation prior to the RACF
      programme.

PMID- 24127766
TI  - Second and third year oral health and dental student perceptions of future
      professional work.
AB  - OBJECTIVES: To explore and compare the ways dental and oral health students
      characterise their future professional work (FPW) at the end of their second and
      third professional years. MATERIALS AND METHODS: Questionnaires were given to a
      cohort group of 48 dental students and 31 oral health students at the end of
      their second and third professional years at the University of Otago. Students'
      characterisations of their FPW were identified using an inductive approach, and
      the emphasis on each characterisation was confirmed using a 'weighted' table.
      RESULTS: Dental student response rates were 92% (in 2010) and 85% (in 2011); and
      oral health student response rates were 100% (in 2011) and 97% (in 2011).
      Students characterised their FPW in ten broad ways: in reference to treatment
      related concerns, patient-related concerns, oral health promotion, oral health
      education, disease prevention and monitoring, communication, teamwork,
      maintaining an ideal clinical environment, maintaining a sense of self and
      improving quality of life. In both years, dental students emphasised treatment
      related concerns as central to their FPW and dealing with patient-related
      concerns as a primary source of difficulty. Oral health students emphasised oral
      health promotion, oral health education, disease prevention and monitoring and
      restorative tasks as central to their FPW and dealing with patient-related
      concerns as a primary source of difficulty. CONCLUSION: Students' broad
      perceptions of their FPW changed little as they progressed through their
      programmes; however, their responses suggested the need for greater attention
      within their programmes to patient management and teamwork.

PMID- 24127768
TI  - The cardiovascular effects of glucagon-like peptide-1 receptor agonists: a trial
      sequential analysis of randomized controlled trials.
AB  - WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists
      are a new class of antidiabetic drugs. Their wider use for the treatment of
      patients with type 2 diabetes mellitus has led to concerns about its
      cardiovascular effects. However, the robustness of data leading to those concerns
      is unclear. The purpose of this study is to systematically assess the robustness
      of the available evidence on the adverse cardiovascular effects of GLP-1 receptor
      agonists in patients with type 2 diabetes. METHODS: The Cochrane library,
      MEDLINE, EMBASE and www.clinicaltrials.gov were searched from inception through
      to 25 January 2013. Randomized controlled trials (RCTs) were selected if they
      compared GLP-1 receptor agonists with placebo or other drugs with a duration >=12
      weeks. Mantel-Haenszel odds ratio (MH-OR) of cardiovascular events with 95%
      confidence interval (CI) was estimated using a random effects model. Trial
      sequential analysis based on required information size with an assumption of
      plausible reductions in relative risk in the low-bias trials, 5% risk of a type I
      error and 20% risk of a type II error was used to explore the robustness of
      available evidence. RESULTS: Fifty-eight trials were included in the analysis (10
      466 patients receiving GLP-1 receptor agonists and 7138 patients receiving
      comparators, respectively). Overall, the OR for cardiovascular events with GLP-1
      receptor agonists was 0.52 (95% CI: 0.27-0.99) compared with placebo and 0.84
      (95% CI: 0.52-1.36) with active controls. Trial sequential analyses showed that
      the actual accumulated sample size was only 11% (7445 of 65 212) and 13% (10 157
      of 79 198) of the required information size for placebo-controlled trials and
      active-controlled trials, respectively. These results indicate that there is
      still insufficient evidence on cardiovascular events. WHAT IS NEW AND CONCLUSION:
      GLP-1 receptor agonists do not seem to show any increased risk of cardiovascular
      events However, the available data from RCTs remain insufficient to confirm an
      absence of detrimental effect. More long-term trials and population-based studies
      are required to provide the necessary reassurance on the cardiovascular safety of
      GLP-1 receptor agonists.

PMID- 24127769
TI  - Cardiac function and arterial indices in infants born small for gestational age:
      analysis by speckle tracking.
AB  - AIM: To compare strain indices between small for gestational age (SGA) infants
      and asymptomatic appropriate for gestational age (AGA) infants and to ascertain
      correlations with arterial biophysical properties. METHODS: In this prospective
      observational echocardiographic study, 20 inborn term SGA infants weighing <3rd
      centile for gestational age were compared with 20 AGA infants. Demographic and
      echocardiographic data were analysed regarding cardiac strain and strain rate and
      arterial indices (stiffness, impedance and strain elastic modulus). Correlations
      between variables were assessed using Pearson's coefficient of correlation.
      RESULTS: Ponderal index was significantly lower in SGA infants (24.6 +/- 2.9 vs.
      29.5 +/- 2.5). Left ventricular global longitudinal strain (GLS) was noted to be
      significantly impaired in the SGA infants (-15.9% +/- 2.1 vs. -21.3% +/- 2.8, p <
      0.001). A basal to apical gradient was noted in segmental strain. Arterial
      biophysical measurements were significantly altered in the SGA infants.
      Significant correlations were noted between GLS and arterial stiffness (r = -0.4,
      p = 0.03), weight-indexed stiffness (r = -0.45, p = 0.02) and pressure-strain
      elastic modulus (r = -0.49, p = 0.01). CONCLUSION: Impairment in myocardial
      deformation was noted in the presence of altered arterial biophysical properties
      in the SGA infants.

PMID- 24127770
TI  - Jugular versus femoral short-term catheterization and risk of infection in
      intensive care unit patients. Causal analysis of two randomized trials.
AB  - RATIONALE: When subclavian access is not possible, controversy exists between the
      internal jugular and femoral sites for the choice of central-venous access in
      intensive care unit patients. OBJECTIVES: To compare infection and colonization
      rates of short-term jugular and femoral catheters. METHODS: Using data from two
      multicenter studies, we compared femoral and internal jugular for the risks of
      catheter-related bloodstream infection, major catheter-related infection, and
      catheter-tip colonization. We also compared the rates of dressing disruption and
      skin colonization. We used marginal structural models with inverse probability of
      treatment weighting to adjust on indication bias. MEASUREMENTS AND MAIN RESULTS:
      We included 2,128 patients (2,527 catheters and 19,481 catheter-days). We found
      no difference in catheter-related bloodstream infection (internal jugular 1.0 vs.
      femoral 1.1 per 1,000 catheter-days; hazard ratio [HR], 0.63 [0.25-1.63]; P =
      0.34), major catheter-related infection (internal jugular 1.8 vs. femoral 1.4 per
      1,000 catheter-days; HR, 0.91 [0.38-2.18]; P = 0.34), and colonization (internal
      jugular 11.6 vs. femoral 12.9 per 1,000 catheter-days; HR, 0.80 [0.25-1.63]; P =
      0.15). However, colonization was higher with femoral for female (HR, 0.39 [0.24
      0.63]; P < 0.001) and, at the significance limit, catheter maintained for more
      than 4 days (HR, 0.73 [0.53-1.01]; P = 0.05). The absence of benefit of internal
      jugular before Day 5 was related to a higher skin colonization at the internal
      jugular site for catheters removed before Day 5. After the fourth day, dressing
      disruption became more frequent with femoral catheters and may explain the
      subsequent risk of catheter colonization. Differences in cutaneous and catheter
      colonization between internal jugular and femoral was suppressed by the use of
      chlorhexidine-impregnated dressings. CONCLUSIONS: Femoral and internal jugular
      accesses lead to similar risks of catheter infection. Internal jugular might be
      preferred for female, nonchlorhexidine-impregnated dressings users, and when
      catheters are left in place more than 4 days. Both sites are acceptable when a
      subclavian approach is not feasible. Clinical trial registered with
      www.clinicaltrials.gov (NCT00417235 and NCT01189682).

PMID- 24127771
TI  - Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol
      dendrimers.
AB  - Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via
      microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules
      as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated
      dendrimers. To produce copper-free antioxidant dendrimers for biological
      applications, Cu(I) was substituted with copper granules. Copper granules were
      ineffective at both room temperature and under reflux conditions (<5% yield).
      However, they were an excellent catalyst when dendrimer synthesis was performed
      under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass
      analysis of the antioxidant dendrimers obtained with this method showed virtually
      no copper contamination (9 ppm), which was the same as the background level. The
      synthesized antioxidants, free from copper contamination, demonstrated potent
      radical scavenging with IC50 values of less than 3 MUM in the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)
      catalyzed click chemistry showed a high level of copper contamination (4800 ppm)
      and no detectable antioxidant activity. 

PMID- 24127772
TI  - Benefits of simultaneous laparoscopic resection of primary colorectal cancer and
      liver metastases.
AB  - INTRODUCTION: Recently, consensus on the optimal strategy for resectable
      synchronous colorectal liver metastases (LM) seems to have shifted toward
      simultaneous resection. However, there are still relatively few reports about
      simultaneous laparoscopic resection. The aim of this study is to evaluate the
      outcomes of patients who underwent simultaneous laparoscopic resection. METHODS:
      We evaluated 14 patients who underwent simultaneous resection of primary
      colorectal cancer and LM in our hospital from 2004 to 2012. Patients were
      selected by matched pair analysis based on the number of LM (<=4) and tumor size
      (<=5 cm). We divided them into two groups: the simultaneous laparoscopic
      resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the
      simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n
      = 7). Clinical and oncologic outcomes were compared between the groups. RESULTS:
      The Lap-S patients were significantly older than the Open-S patients. The mean
      operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The
      mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the
      Open-S group (496 mL). There was no surgical mortality in either group. The
      incidence of postoperative complications in the Lap-S and Open-S groups was 12.3%
      and 33.0%, respectively. The mean postoperative hospital stay was significantly
      shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There
      was no significant difference in long-term survival between the two groups.
      CONCLUSION: Lap-S patients had equivalent long-term outcomes to Open-S patients.
      Therefore, given its technical feasibility and safety, Lap-S may be one of the
      most promising options in selected patients.

PMID- 24127773
TI  - Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for
      robot-assisted laparoscopic surgery.
AB  - OBJECTIVE: To assess critical heat spread of cautery instruments used in robot
      assisted laparoscopic (RAL) surgery. MATERIALS AND METHODS: Thermal spread along
      bovine musculofascial tissues was examined by infrared camera, histology and
      enzyme assay. Currently used monopolar, bipolar and ultrasonic laparoscopic
      instruments were investigated at various power settings and application times.
      The efficacy of using an additional Maryland clamp as a heat sink was evaluated.
      A temperature of 45  degrees C was considered the threshold temperature for
      possible nerve damage. RESULTS: Monopolar instruments exhibited a mean (sem)
      critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s,
      the spread was >20 mm. For adjustable bipolar instruments the mean (sem) critical
      thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s. The PK
      and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8
      (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm.
      Application of an additional Maryland clamp as a heat sink, significantly reduced
      the thermal spread. Histomorphometric analyses and enzyme assay supported these
      findings. CONCLUSIONS: All coagulation devices used in RAL surgery have distinct
      thermal spreads depending on power setting and application time. Cautery may be
      of concern due to lateral temperature spread, causing potential damage to
      sensitive structures including nerves. Our results provide surgeons with a
      resource for educated decision-making when using coagulation devices during
      robotic procedures.

PMID- 24127775
TI  - High-grade mucoepidermoid carcinoma of the columella successfully reconstructed
      using bilateral nasolabial flaps set up in a sandwich shape and an auricular
      cartilage graft after surgical resection.
AB  - Mucoepidermoid carcinoma (MEC) usually originates from the salivary glands.
      However, there has been no report on mucoepidermoid carcinoma of the columella.
      In this study, we report the case of a high-grade MEC of the columella that was
      successfully reconstructed after surgical resection with bilateral nasolabial
      flaps set up in a sandwich shape and an auricular cartilage graft. A 66-year-old
      man presented with a nodule on the columella. Histological findings were
      suggestive of a high-grade mucoepidermoid carcinoma. Wide excision was performed,
      and the defects of the columella and the nasal floor were reconstructed with
      bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage
      graft. The postoperative cosmetic result was good with excellent tissue texture.
      The reconstructed columella had an appropriate, not bulky, width as well as
      satisfactory height and depth. This reconstructive technique is particularly
      useful for correcting the large defect of the columella with nasal septum and/or
      nasal floor defects. 

PMID- 24127774
TI  - Role of IL-4Ralpha during acute schistosomiasis in mice.
AB  - Schistosomiasis is an important parasitic disease that causes major host
      morbidity and mortality in endemic areas. Research conducted in mouse models of
      schistosomiasis has provided great insights and understanding of how host
      protective immunity is orchestrated and key cellular populations involved in this
      process. Earlier studies using cytokine-deficient mice demonstrated the
      importance of IL-4 and IL-10 in mediating host survival during acute
      schistosomiasis. Subsequent studies employing transgenic mice carrying cell
      specific deletion of IL-4Ralpha generated using the Cre/LoxP recombination system
      have been instrumental in providing more in-depth understanding of the mechanisms
      conferring host resistance to Schistosoma mansoni infection. In this review, we
      will summarize the contributions of IL-4/IL-13-responsive cellular populations in
      host resistance during acute schistosomiasis and their role in limiting tissue
      pathology. 

PMID- 24127776
TI  - Protonation-induced chromism of pyridylethynyl-appended [core+exo]-type Au8
      clusters. Resonance-coupled electronic perturbation through pi-conjugated group.
AB  - A series of [core+exo]-type Au8 clusters bearing two alkynyl ligands on the exo
      gold atoms ([Au8(dppp)4(C=CR)2](2+), 2-6) were synthesized by the reaction of
      [Au8(dppp)4](2+) (1) with alkynyl anions. Although the C=C moieties directly
      attached to the Au8 units did not affect the optical properties arising from
      intracluster transitions, the pyridylethynyl-bearing clusters (4-6) exhibited
      reversible visible absorption and photoluminescence responses to
      protonation/deprotonation events of the terminal pyridyl moieties. The chromism
      behaviors and proton-binding constants of these clusters were highly dependent on
      the relative position of the pyridine nitrogen atom, such that the 2-pyridyl (4)
      and 4-pyridyl (6) isomers showed more pronounced responses than the 3-pyridyl
      isomer (5). These results suggest that the resonance-coupled movement of the
      positive charge upon protonation is involved in the optical responses, where the
      formation of extended charged resonance structures causes significant
      perturbation effects on the electronic properties of the Au8 unit and also
      contributes to the high binding affinities. 

PMID- 24127777
TI  - Dendrimer space exploration: an assessment of dendrimers/dendritic scaffolding as
      inhibitors of protein-protein interactions, a potential new area of
      pharmaceutical development.

PMID- 24127779
TI  - Investigating the association of lactation history and postmenopausal breast
      cancer risk in the Women's Health Initiative.
AB  - Prolonged lactation (>=24 mo) has been associated with reduced breast cancer
      risk. This research examined this association in postmenopausal women in the
      Women's Health Initiative (WHI) Hormone Trial (HT) and Observational Study (OS).
      This retrospective cohort analysis included 69,358 predominantly overweight
      (65.4%), white (83.2%) postmenopausal women without breast cancer. Women in the
      HT were randomized to 0.625 mg conjugated equine estrogen (CEE), 0.625 CEE + 2.5
      mg medroxyprogesterone acetate (CEE/MPA), or placebo. OS participants had no
      restrictions on hormone use. Lactation history was assessed via WHI Reproductive
      History Questionnaire. Most women breastfed at least 1 mo (58.0%); 35.4%
      breastfed 1-2 children; and 6.5% stated having breastfed >=24mo. Women in the HT
      CEE who breastfed their first child between 20-24 yr of age demonstrated a
      nonsignificant decreased risk of breast cancer (HR: 0.62; 95% CI: 0.38, 1.01). OS
      participants who reported CEE/MPA hormone use and age of first breastfeeding >=30
      yr showed a significant increased risk of breast cancer (HR: 1.66; 95% CI: 1.14,
      2.41). Risk was increased if age of last breastfeeding was >=35yr (HR: 1.50; 95%
      CI: 1.05, 2.14). This research did not demonstrate a significantly decreased risk
      of postmenopausal breast cancer in women who breastfed for >=24 mo during their
      lifetime. 

PMID- 24127781
TI  - Effect of the 12-gene colon cancer assay results on adjuvant treatment
      recommendations in patients with stage II colon cancer.
AB  - INTRODUCTION: The 12-gene colon cancer Recurrence Score assay is a clinically
      validated predictor of recurrence risk in stage II colon cancer patients. A
      survey was performed characterizing the assay's impact on treatment
      recommendations for these patients. METHODS: US medical oncologists (n = 346) who
      ordered the assay for >=3 stage II colon cancer patients were asked to complete a
      web-based survey regarding their most recent such patient. Physicians surveyed
      represented users of the assay within the first 2 years of commercial
      availability which may include 'early adopters'. RESULTS: Most of 116 eligible
      physicians were in community practice (86%), with median 14.5 years' experience
      (range = 2-40). Mean patient age was 61 years (range = 32-85); 81% had T3
      disease, and 38% had comorbidities. Of 76 patients tested for mismatch
      repair/microsatellite-instability (MMR/MSI), 13 (17%) were MMR-deficient/MSI
      high; 46 (61%) MMR-proficient/MSI-low; and 17 (22%) unknown. Most patients (84%)
      had >=12 nodes examined. Median Recurrence Score result was 20 (range = 1-77).
      Before assay, treatment recommendations were specified for 92 (79%) patients,
      with no recommendation for 24 (21%). Of the 92 with pre-assay recommendations,
      chemotherapy was planned for 52 (57%) and observation for 40 (43%); the assay
      changed recommendations for 27 (29%). Treatment intensity decreased for 18 (67%)
      and increased for nine (33%) patients; it was more likely to decrease for lower
      Recurrence Score values and increase for higher values (p < 0.001). CONCLUSION:
      For stage II colon cancer patients receiving Recurrence Score testing, 29% of
      treatment recommendations were changed. Use of the assay may lead to reductions
      in treatment intensity. Study limitations include retrospective design, data
      gathering during the first 2 years of assay availability only, and potential non
      representativeness of respondents.

PMID- 24127780
TI  - Regulation of the high-affinity choline transporter activity and trafficking by
      its association with cholesterol-rich lipid rafts.
AB  - The sodium-coupled, hemicholinium-3-sensitive, high-affinity choline transporter
      (CHT) is responsible for transport of choline into cholinergic nerve terminals
      from the synaptic cleft following acetylcholine release and hydrolysis. In this
      study, we address regulation of CHT function by plasma membrane cholesterol. We
      show for the first time that CHT is concentrated in cholesterol-rich lipid rafts
      in both SH-SY5Y cells and nerve terminals from mouse forebrain. Treatment of SH
      SY5Y cells expressing rat CHT with filipin, methyl-beta-cyclodextrin (MbetaC) or
      cholesterol oxidase significantly decreased choline uptake. In contrast, CHT
      activity was increased by addition of cholesterol to membranes using cholesterol
      saturated MbetaC. Kinetic analysis of binding of [(3)H]hemicholinium-3 to CHT
      revealed that reducing membrane cholesterol with MbetaC decreased both the
      apparent binding affinity (KD) and maximum number of binding sites (Bmax ); this
      was confirmed by decreased plasma membrane CHT protein in lipid rafts in cell
      surface protein biotinylation assays. Finally, the loss of cell surface CHT
      associated with lipid raft disruption was not because of changes in CHT
      internalization. In summary, we provide evidence that CHT association with
      cholesterol-rich rafts is critical for transporter function and localization.
      Alterations in plasma membrane cholesterol cholinergic nerve terminals could
      diminish cholinergic transmission by reducing choline availability for
      acetylcholine synthesis. The sodium-coupled choline transporter CHT moves choline
      into cholinergic nerve terminals to serve as substrate for acetylcholine
      synthesis. We show for the first time that CHT is concentrated in cholesterol
      rich lipid rafts, and decreasing membrane cholesterol significantly reduces both
      choline uptake activity and cell surface CHT protein levels. CHT association with
      cholesterol-rich rafts is critical for its function, and alterations in plasma
      membrane cholesterol could diminish cholinergic transmission by reducing choline
      availability for acetylcholine synthesis.

PMID- 24127782
TI  - Gold nanocrystal labeling allows low-density lipoprotein imaging from the
      subcellular to macroscopic level.
AB  - Low-density lipoprotein (LDL) plays a critical role in cholesterol transport and
      is closely linked to the progression of several diseases. This motivates the
      development of methods to study LDL behavior from the microscopic to whole-body
      level. We have developed an approach to efficiently load LDL with a range of
      diagnostically active nanocrystals or hydrophobic agents. We performed focused
      experiments on LDL labeled with gold nanocrystals (Au-LDL). The labeling
      procedure had minimal effect on LDL size, morphology, or composition. Biological
      function was found to be maintained from both in vitro and in vivo experiments.
      Tumor-bearing mice were injected intravenously with LDL, DiR-LDL, Au-LDL, or a
      gold-loaded nanoemulsion. LDL accumulation in the tumors was detected with whole
      body imaging methods, such as computed tomography (CT), spectral CT, and
      fluorescence imaging. Cellular localization was studied with transmission
      electron microscopy and fluorescence techniques. This LDL labeling procedure
      should permit the study of lipoprotein biointeractions in unprecedented detail. 

PMID- 24127784
TI  - Long-term survival of high quality sperm: insights into the sperm proteome of the
      honeybee Apis mellifera.
AB  - In the social bees, ants, and wasps, females (queens) mate only during a brief
      period early in their lives and afterward store a lifetime supply of sperm in a
      specialized organ, the spermatheca. In some species, stored sperm can remain
      viable for several decades and is used by queens to fertilize millions of eggs.
      The physiological adaptations that allow this prolonged survival are unknown. To
      unravel them, we conducted proteomic analyses on the sperm of the honeybee Apis
      mellifera to define proteins that are bee-specific or highly divergent from
      sequences in the sperm proteomes of flies or mammals and might therefore be
      associated with long-term sperm survival. We identified a honeybee sperm proteome
      of 336 members and defined the subset of proteins or protein networks that cannot
      be discerned in the sperm proteomes of fruit flies and humans. This subset
      contained a significant number of proteins that are predicted to act in enzyme
      regulation or in nucleic acid binding and processing. From our analysis we
      conclude that long-term survival of sperm in social insects could be underpinned
      by substantial changes in only a specific subset of sperm proteins that allow
      physiological adaptation to storage. The unexpected preponderance of proteins
      predicted to be involved in transcriptional processes and enzyme regulation
      suggest these are the primary targets of this adaptation. 

PMID- 24127783
TI  - Hepatitis C virus-specific cellular immune responses in sustained virological
      responders with viral persistence in peripheral blood mononuclear cells.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV)-RNA detection in peripheral blood
      mononuclear cells (PBMCs) after recovery from HCV infection, is a type of occult
      HCV infection although is unclear how the viral persistence in PBMCs affects HCV
      specific T-cell responses. The aim of this study was to investigate if cellular
      immune responses are modified by HCV persistence in PBMCs. METHODS: HCV-specific
      CD4(+) and CD8(+) T-cell responses against six HCV peptides, situated within the
      non-structural (NS) proteins NS3, NS4b and NS5b, were measured by flow cytometry
      through intracellular detection of gamma interferon (IFN-gamma) or interleukin 4
      (IL-4) and CD69 expression- in 27 sustained virological responders (SVR): 13 with
      and 14 without occult HCV infection in PBMCs, detected by strand-specific real
      time PCR. Ten healthy individuals and 14 chronically infected patients with
      viraemia, were included as controls. RESULTS: SVR without occult infection showed
      a higher percentage of activated CD4(+) cells against peptides belonging to NS3
      (p124, p153) and NS5b (p257, p294), activated CD8(+) cells against NS3 (p124,
      p153, p158) and NS5b-p294, as well as an elevated percentage of CD4(+) cells
      releasing IFN-gamma + IL-4 against NS3-p153, and by CD8(+) cells against NS3
      (p124, p153). SVR without occult infection showed a higher percentage of
      activation and release of IFN-gamma + IL-4 by both cell subpopulations than the
      two group of controls, in contrast to SVR with occult infection. CONCLUSION: The
      lower HCV-specific T-cell response found in SVR with occult infection indicates
      that the immune response may be impaired when the virus persists in PBMCs.

PMID- 24127785
TI  - Strong anion determination in biological fluids by capillary electrophoresis for
      clinical diagnostics.
AB  - New methods for quantitative analysis of strong anions are required for
      diagnostic testing of human diseases. Current techniques suffer from poor
      selectivity and/or long analysis times that are not amenable for labile anions in
      high-saline or volume-restricted samples. We introduce a rapid assay (<5 min)
      based on capillary electrophoresis (CE) with indirect UV detection for
      simultaneous analysis of sulfate, sulfite, and chloride in human urine, plasma,
      and sweat specimens. Remarkable selectivity for strong anions is achieved by
      using an acidic background electrolyte under reversed polarity that results in
      electrokinetic rejection of matrix interferences at the capillary inlet. A dual
      co-ion probe system consisting of 5 mM naphthalene disulfonate (NDS) and 5 mM
      naphthalene trisulfonate (NTS) in 0.4 M formic acid, pH 2.0 is developed for
      detection of UV transparent anions (S/N ~ 3, 60 MUM with a 25 MUm inner diameter
      fused-silica capillary) with good peak symmetry and baseline stability. Due to
      the chemical reactivity of sulfite, dilute formaldehyde is used as a reagent to
      form an acid-stable hydroxymethylsulfonate adduct. Method validation confirmed
      excellent linearity (R(2) > 0.999), good accuracy (mean bias ~7%), and acceptable
      long-term reproducibility (CV < 10%) over 20 days. The assay allows for artifact
      free determination of sulfate and sulfite with consistent results for chloride
      when compared to standard electrochemical methods (R(2) > 0.975). Preliminary
      data suggest that kidney-stone formers have lower urinary sulfate excretion
      relative to non-kidney-stone patient controls (p = 0.0261). CE offers a selective
      yet robust platform for routine analysis of strong anions that is needed for
      confirmatory testing of cystic fibrosis, sulfite oxidase deficiency,
      urolithiasis, and other disorders of sulfur metabolism and/or anion transport. 

PMID- 24127786
TI  - Zener tunneling and photocurrent generation in quasi-metallic carbon nanotube pn
      devices.
AB  - We investigate the electronic and optoelectronic properties of quasi-metallic
      nanotube pn-devices, which have smaller band gaps than most known bulk
      semiconductors. These carbon nanotube-based devices deviate from conventional
      bulk semiconductor device behavior due to their low-dimensional nature. We
      observe rectifying behavior based on Zener tunneling of ballistic carriers
      instead of ideal diode behavior, as limited by the diffusive transport of
      carriers. We observe substantial photocurrents at room temperature, suggesting
      that these quasi-metallic pn-devices may have a broader impact in optoelectronic
      devices. A new technique based on photocurrent spectroscopy is presented to
      identify the unique chirality of nanotubes in a functional device. This chirality
      information is crucial in obtaining a theoretical understanding of the underlying
      device physics that depends sensitively on nanotube chirality, as is the case for
      quasi-metallic nanotube devices. A detailed model is developed to fit the
      observed I-V characteristics, which enables us to verify the band gap from these
      measurements as well as the dimensions of the insulating tunneling barrier
      region. 

PMID- 24127787
TI  - Determinants of gross motor function of young children with cerebral palsy: a
      prospective cohort study.
AB  - AIM: The aim of this study was to test a model of determinants of gross motor
      function of young children with cerebral palsy (CP). METHOD: Four hundred and
      twenty-nine children with CP (242 males, 187 females; mean age 3 y 2 mo, SD 11
      mo) representing all levels of the Gross Motor Function Classification System
      (GMFCS) participated. Children in levels I to II and III to V were classified as
      Groups 1 and 2 respectively. Distribution of CP was quadriplegia, 44%;
      hemiplegia, 24%; diplegia, 23%; triplegia, 6%; and monoplegia, 2% (data not
      available for 1%). Impairment and motor function data were collected by reliable
      assessors; parents completed questionnaires on health conditions and adaptive
      behavior. Seven months later, parents were interviewed about family life and
      services received. One year after the study onset, motor function was re
      evaluated. Analysis involved structural equation modeling. RESULTS: The well
      fitting model explained 58% and 75% of the variance in motor function at study
      completion for Groups 1 and 2 respectively. Primary impairments (spasticity,
      quality of movement, postural stability, and distribution of involvement;
      beta=0.52-0.68) and secondary impairments (strength, range of motion limitations,
      and reduced endurance; beta=0.25-0.26) explained the most variance. Adaptive
      behavior was a significant determinant only for Group 2 (beta=0.21) and
      participation in community programs was significant only in Group 1 (beta=0.13).
      INTERPRETATION: Motor function is supported by optimizing body structures and
      function for all children and enhancing adaptive behavior for children with
      greater motor challenges.

PMID- 24127788
TI  - Reduced burden of very large and rare CNVs in bipolar affective disorder.
AB  - OBJECTIVES: Large, rare chromosomal copy number variants (CNVs) have been shown
      to increase the risk for schizophrenia and other neuropsychiatric disorders
      including autism, attention-deficit hyperactivity disorder, learning
      difficulties, and epilepsy. Their role in bipolar disorder (BD) is less clear.
      There are no reports of an increase in large, rare CNVs in BD in general, but
      some have reported an increase in early-onset cases. We previously found that the
      rate of such CNVs in individuals with BD was not increased, even in early-onset
      cases. Our aim here was to examine the rate of large rare CNVs in BD in
      comparison with a new large independent reference sample from the same country.
      METHODS: We studied the CNVs in a case-control sample consisting of 1,650 BD
      cases (reported previously) and 10,259 reference individuals without a known
      psychiatric disorder who took part in the original Wellcome Trust Case Control
      Consortium (WTCCC) study. The 10,259 reference individuals were affected with six
      non-psychiatric disorders (coronary artery disease, types 1 and 2 diabetes,
      hypertension, Crohn's disease, and rheumatoid arthritis). Affymetrix 500K array
      genotyping data were used to call the CNVs. RESULTS: The rate of CNVs > 100 kb
      was not statistically different between cases and controls. The rate of very
      large (defined as > 1 Mb) and rare (< 1%) CNVs was significantly lower in
      patients with BD compared with the reference group. CNV loci associated with
      schizophrenia were not enriched in BD and, in fact, cases of BD had the lowest
      number of such CNVs compared with any of the WTCCC cohorts; this finding held
      even for the early-onset BD cases. CONCLUSIONS: Schizophrenia and BD differ with
      respect to CNV burden and association with specific CNVs. Our findings support
      the hypothesis that BD is etiologically distinct from schizophrenia with respect
      to large, rare CNVs and the accompanying associated neurodevelopmental
      abnormalities.

PMID- 24127789
TI  - Abstracts of the XXVI Congress of the Spanish Society for Clinical Pharmacology.
      October 17-18, 2013. Cadiz, Spain.

PMID- 24127790
TI  - Daily parenting engagement among new mothers and fathers: the role of romantic
      attachment in dual-earner families.
AB  - We investigated the association of prenatal assessments of mothers' and fathers'
      self-reported romantic attachment anxiety and avoidance with the time mothers and
      fathers reported in proximity-focused and exploration-focused engagement with
      their infants at 9 months postpartum. Our sample of 136 dual-earner couples came
      from a larger longitudinal study of the transition to parenthood. Time in
      proximity-focused (interactions that emphasize physical or emotional connection)
      and exploration-focused (activities that stimulate and build knowledge of the
      world) engagement on workdays and nonworkdays were measured using time diaries.
      Using actor-partner interdependence models, we found significant across-partners
      associations between romantic attachment and parental engagement. In particular,
      analyses revealed interesting interactions: fathers higher in avoidance spent
      more time in exploration-focused engagement on workdays when mothers were more
      anxious, whereas mothers higher in anxiety spent more time in proximity-focused
      engagement on nonworkdays when fathers were more avoidant. Moreover, fathers
      demonstrated a compensatory pattern of engagement in response to mother's greater
      attachment anxiety or avoidance. Findings support the utility of studying
      romantic attachment within a family system and extend the literature on
      correlates of early parental engagement.

PMID- 24127791
TI  - Cobalt-free nickel rich layered oxide cathodes for lithium-ion batteries.
AB  - We propose a feasibility of Co-free Ni-rich Li(Ni(1-x)Mn(x))O2 layer compound.
      Li(Ni(1-x)Mn(x))O2 (0.1 <= x <= 0.5) have been synthesized by a coprecipitation
      method. Rietveld refinement of X-ray diffraction and microscopic studies reveal
      dense and spherical secondary particles of highly crystalline phase with low
      cation mixing over the whole compositions, implying successful optimization of
      synthetic conditions. Electrochemical test results indicated that the Co-free
      materials delivered high capacity with excellent capacity retention and
      reasonable rate capability. In particular, Li(Ni0.9Mn0.1)O2, which possesses the
      lowest cation mixing in the Li layers among samples, exhibited exceptionally high
      rate capacity (approximately 149 mAh g(-1) at 10 C rate) at 25  degrees C and
      high discharge capacity upon cycling under a severe condition, in the voltage
      range of 2.7-4.5 V at 55  degrees C. The cation mixing in Li(Ni0.9Mn0.1)O2
      increased slightly even after the extensive cycling at the elevated temperature,
      which is ascribed to the structural integrity induced from the optimized
      synthetic condition using the coprecipitation.

PMID- 24127792
TI  - A study of the eigenvectors of the low-frequency vibrational modes in crystalline
      adenosine via high pressure Raman spectroscopy.
AB  - High-pressure Raman spectroscopy has been used to study the eigenvectors and
      eigenvalues of the vibrational modes of crystalline adenosine at 295 K by
      evaluating the logarithmic derivative of the vibrational frequency with respect
      to pressure: [Formula: see text]. Crystalline samples of molecular materials such
      as adenosine will have vibrational modes that are localized within a molecular
      unit ("internal" modes) as well as modes in which the molecular units vibrate
      against each other ("external" modes). The value of the logarithmic derivative is
      found to be a diagnostic probe of the nature of the eigenvector of the
      vibrational modes. Stretching modes which are predominantly internal to the
      molecule have low logarithmic derivatives while external modes have higher
      logarithmic derivatives. Particular interest is paid to the low-frequency (<=150
      cm(-1)) modes. Based on the pressure dependence of its logarithmic derivative, a
      mode near 49 cm(-1) is identified as internal mode. The other modes below 400 cm(
      1) have pressure dependences of their logarithmic derivatives consistent with
      being either (1) modes which are mainly external, meaning that the molecules of
      the unit cell vibrate against each other in translational or librational motions
      (or linear combinations thereof), or (2) torsional or bending modes involving a
      large number of atoms, mainly within a molecule. The modes above 400 cm(-1) all
      have pressure dependences of their logarithmic derivatives consistent with being
      mainly internal modes. 

PMID- 24127793
TI  - Allergic to autotaxin. A new role for lysophospholipase d and lysophosphatidic
      Acid in asthma?

PMID- 24127794
TI  - The future of nature versus nurture in understanding chronic obstructive
      pulmonary disease.

PMID- 24127795
TI  - Receptor for advanced glycation end products and soluble receptor for advanced
      glycation end products: a balancing act in chronic obstructive pulmonary disease?

PMID- 24127796
TI  - Liberating brain-injured patients from mechanical ventilation. learning from
      healthcare delivery science.

PMID- 24127797
TI  - Community-acquired pneumonia versus healthcare-associated pneumonia. The
      returning pendulum.

PMID- 24127798
TI  - Emergence of obstructive sleep apnea phenotyping. From weak to strong!

PMID- 24127799
TI  - Update in tuberculosis and nontuberculous mycobacterial disease 2012.
AB  - In 2012, new publications in the Journal described both the predictive value of
      the new IFN-gamma release assays for diagnosis of latent tuberculosis (TB), but
      also provided evidence that these new tests cannot be interpreted simply as
      positive or negative, as initially hoped. Surgical masks can reduce transmission
      of TB infection, but other measures such as state-wide implementation of targeted
      testing and treatment of latent TB or active case finding require substantial and
      sustained effort to successfully reduce TB morbidity and mortality. A
      quasiexperimental study revealed that a package of social interventions could
      substantially reduce risk of TB disease in heavily exposed (and infected)
      children in the preantibiotic era. A study in a high-TB burden setting suggested
      that a new rapid drug-susceptibility test for TB may be more practical for
      implementation than traditional culture-based phenotypic tests. And two studies
      of TB vaccines revealed that currently used bacillus Calmette-Guerin strains vary
      in their ability to affect correlates of immunogenicity, whereas a new candidate
      vaccine, MVA85A, was safe and immunogenic in adults. Studies of nontuberculous
      mycobacteria (NTM) described a rapid rise in the prevalence and spatial
      clustering of NTM in the United States over the past decade. Although risk
      factors for pulmonary NTM such as advanced age and low BMI are known, the
      mechanisms underlying infection and disease remain mysterious. Four studies of
      therapy of NTM disease highlighted the pressing need for well-designed
      international randomized controlled trials to improve our management of NTM
      disease. 

PMID- 24127800
TI  - Lung-on-a-chip microdevice, right ventricular dysfunction as a predictor of
      survival, and lung ultrasound in community-acquired pneumonia.

PMID- 24127801
TI  - Congenital pulmonary airway malformation presenting as unilateral cystic lung
      disease.

PMID- 24127802
TI  - Amphotericin B in severe fungal infections: a critical reappraisal of the
      evidence.

PMID- 24127803
TI  - Reply: continuous infusion of amphotericin B deoxycholate for the treatment of
      life-threatening Candida infections.

PMID- 24127804
TI  - Continuous infusion of amphotericin B deoxycholate for the treatment of life
      threatening Candida infections.

PMID- 24127805
TI  - Stage shift in computed tomography screening: possible role of indolent cancers,
      "histology shift," and overdiagnosis.

PMID- 24127806
TI  - Reply: stage distribution of lung cancers detected by computed tomography
      screening in the NELSON Trial.

PMID- 24127807
TI  - Tropheryma whipplei pneumonia in a patient with HIV-2 infection.

PMID- 24127808
TI  - Nonischemic myocardial changes detected by cardiac magnetic resonance in critical
      care patients with sepsis.

PMID- 24127809
TI  - Plasma chemokines in early wheezers predict the development of allergic asthma.

PMID- 24127810
TI  - Neonatal airway colonization is associated with troublesome lung symptoms in
      infants.

PMID- 24127812
TI  - Nontuberculous empyema necessitatis.

PMID- 24127811
TI  - An official American Thoracic Society/European Respiratory Society statement: key
      concepts and advances in pulmonary rehabilitation.
AB  - BACKGROUND: Pulmonary rehabilitation is recognized as a core component of the
      management of individuals with chronic respiratory disease. Since the 2006
      American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on
      Pulmonary Rehabilitation, there has been considerable growth in our knowledge of
      its efficacy and scope. PURPOSE: The purpose of this Statement is to update the
      2006 document, including a new definition of pulmonary rehabilitation and
      highlighting key concepts and major advances in the field. METHODS: A
      multidisciplinary committee of experts representing the ATS Pulmonary
      Rehabilitation Assembly and the ERS Scientific Group 01.02, "Rehabilitation and
      Chronic Care," determined the overall scope of this update through group
      consensus. Focused literature reviews in key topic areas were conducted by
      committee members with relevant clinical and scientific expertise. The final
      content of this Statement was agreed on by all members. RESULTS: An updated
      definition of pulmonary rehabilitation is proposed. New data are presented on the
      science and application of pulmonary rehabilitation, including its effectiveness
      in acutely ill individuals with chronic obstructive pulmonary disease, and in
      individuals with other chronic respiratory diseases. The important role of
      pulmonary rehabilitation in chronic disease management is highlighted. In
      addition, the role of health behavior change in optimizing and maintaining
      benefits is discussed. CONCLUSIONS: The considerable growth in the science and
      application of pulmonary rehabilitation since 2006 adds further support for its
      efficacy in a wide range of individuals with chronic respiratory disease.

PMID- 24127813
TI  - Transcatheter closure of coronary arterial fistula in children and adolescents.
AB  - BACKGROUND: Transcatheter closure of coronary arterial fistula (CAF) is being
      utilized increasingly as an alternative to surgical closure, but most of the
      literature on transcatheter closure of CAF in children and adolescents consists
      of case reports and reports of small series. The aim of this study was therefore
      to describe our experience of percutaneous closure of CAF in children and
      adolescents. METHODS: Between April 1998 and December 2012, 37 children and
      adolescents with congenital CAF underwent percutaneous transcatheter closure.
      After aortic root angiography and selective coronary angiography, a guidewire was
      positioned to the fistula. In some cases, an arteriovenous wire loop (AV loop)
      was created. The sheath passed along the wire to the site of the desired
      occlusion of the fistula. One or more occlusion devices were selected to embolize
      the fistula. RESULTS: Occlusion devices were placed in 33 procedures (32
      patients). Occlusion was unsuccessful in five patients. Duct occluders were
      placed in 12 procedures, coils in 11 (10 patients), muscular ventricular septal
      occluders in six, and vascular plugs in four procedures. The tricuspid valve was
      injured in two patients. One patient with a giant CAF aneurysm had a thrombosis
      within the aneurysm after transcatheter closure. There were no deaths, fistula
      dissection or myocardial infarction. CONCLUSION: Transcatheter closure of CAF is
      feasible in anatomically suitable cases, but injury to the tricuspid valve
      involved with AV loop methods can occur in closure procedures, and thrombus
      formation is possible in the blind pouch of the residual fistula after closure.
      Long-term follow up after fistula closure is necessary.

PMID- 24127814
TI  - Selected family characteristics are associated with adolescents' subjective
      health complaints.
AB  - AIM: This national study of schoolchildren in Greece investigated the association
      between adolescents' subjective health complaints (SHC) and a number of family
      characteristics. METHODS: Questionnaires were completed by a random, school-based
      sample of children from 12 to 18 years of age, and one of their parents (76.6%
      mothers), in 2003. Data from 1041 adolescent-parent pairs were analysed. Multiple
      linear regression analysis was used to assess the associations between the
      adolescent's SHC and the following characteristics: parent's marital status,
      parent's physical and mental health status, parent's worries about their child's
      SHC, the parent-child relationship, family cohesion, family socio-economic status
      and the adolescent's sex and age. RESULTS: The analysis showed that the
      adolescents' SHC were independently and significantly correlated with poor
      parental subjective mental health status, poor quality parent-child relationships
      and parental worry. There were also associations between levels of SHC and female
      and older adolescents. CONCLUSION: Certain family features can be seen as
      potential contributing factors to SHC in adolescence and should therefore
      constitute complementary targets for prevention and treatment planning.

PMID- 24127815
TI  - Hyponatraemia in cancer patients on an inpatient rehabilitation unit.
AB  - This study identifies the incidence of hyponatraemia in cancer patients on an
      inpatient rehabilitation unit and examines the association between admission
      hyponatraemia and rehabilitation length of stay (LOS), functional outcome, and
      survival. After institutional review committee's approval, we retrospectively
      reviewed medical records of 295 consecutive patients who were admitted to this
      inpatient cancer rehabilitation unit between 27 January 2009 through 31 July 2010
      in a tertiary cancer centre. The incidence of hyponatraemia in cancer patients
      admitted to our inpatient rehabilitation unit was 41.4%. Median rehabilitation
      LOS for patients with mild (Na 130-134 mEq/L) and moderate-severe (Na < 130
      mEq/L) hyponatraemia was 11 and 15 days, respectively, which was significantly
      longer than patients with eunatraemia (10 days; P = 0.03). Functional
      Independence Measure gain for ambulation and transfers during inpatient
      rehabilitation stay was not significantly different between three different
      patient groups. We concluded that large portion of patients who require acute
      inpatient rehabilitation presented with hyponatraemia, which is associated with
      prolonged rehabilitation LOS. Whether aggressive management of hyponatraemia will
      shorten rehabilitation stay needs further study.

PMID- 24127817
TI  - Kink characterization and modeling in transmembrane protein structures.
AB  - Kinks have been observed to provide important functional and structural features
      for membrane proteins. Despite their ubiquity in membrane proteins, and their
      perceived importance, no protein modeling methods explicitly considers kinks. In
      spite of the limited data for transmembrane proteins, we were able to develop a
      knowledge-based modeling method for introducing kinks, which we demonstrate can
      be exploited in modeling approaches to improve the quality of models. The work
      entailed a thorough analysis of the available high resolution membrane protein
      structures, concomitantly demonstrating the complexity of the structural
      considerations for kink prediction. Furthermore, our results indicate that there
      are systematic and significant differences in the sequence as well as the
      structural environment between kinked and nonkinked transmembrane helices. To the
      best of our knowledge, we are reporting a method for modeling kinks for the first
      time. 

PMID- 24127816
TI  - A cross-sectional analysis of light at night, neighborhood sociodemographics and
      urinary 6-sulfatoxymelatonin concentrations: implications for the conduct of
      health studies.
AB  - BACKGROUND: There is accumulating evidence that circadian disruption, mediated by
      alterations in melatonin levels, may play an etiologic role in a wide variety of
      diseases. The degree to which light-at-night (LAN) and other factors can alter
      melatonin levels is not well-documented. Our primary objective was to evaluate
      the degree to which estimates of outdoor environmental LAN predict 6
      sulftoxymelatonin (aMT6s), the primary urinary metabolite of melatonin. We also
      evaluated other potential behavioral, sociodemographic, and anthropomorphic
      predictors of aMT6s. METHODS: Study participants consisted of 303 members of the
      California Teachers Study who provided a 24-hour urine specimen and completed a
      self-administered questionnaire in 2000. Urinary aMT6s was measured using the
      Buhlmann ELISA. Outdoor LAN levels were estimated from satellite imagery data
      obtained from the U.S. Defense Meteorological Satellite Program's (DMSP)
      Operational Linescan System and assigned to study participants' geocoded
      residential address. Information on other potential predictors of aMT6s was
      derived from self-administered surveys. Neighborhood socioeconomic status (SES)
      was based on U.S. Census block group data. RESULTS: Lower aMT6s levels were
      significantly associated with older age, shorter nights, and residential
      locations in lower SES neighborhoods. Outdoor sources of LAN estimated using low
      dynamic range DMSP data had insufficient variability across urban neighborhoods
      to evaluate. While high-dynamic range DMSP offered much better variability, it
      was not significantly associated with urinary aMT6s. CONCLUSIONS: Future health
      studies should utilize the high-dynamic range DMSP data and should consider other
      potential sources of circadian disruption associated with living in lower SES
      neighborhoods.

PMID- 24127818
TI  - Influence of baseline variables on changes in International Prostate Symptom
      Score after combined therapy with dutasteride plus tamsulosin or either
      monotherapy in patients with benign prostatic hyperplasia and lower urinary tract
      symptoms: 4-year results of the CombAT study.
AB  - OBJECTIVE: To examine, using post hoc analysis, the influence of baseline
      variables on changes in international prostate symptom score (IPSS), maximum
      urinary flow rate (Qmax ) and IPSS quality of life (QoL) in patients with
      moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic
      hyperplasia (BPH) treated with either the alpha-blocker tamsulosin or the dual 5
      alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4
      year Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS:
      CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study
      in 4844 men >=50 years of age with a clinical diagnosis of BPH by medical history
      and physical examination, an IPSS >=12 points, prostate volume (PV) >=30 mL,
      total serum PSA level >=1.5 ng/mL, and Qmax >5 mL/s and <=15 mL/s with a minimum
      voided volume >=125 mL. Eligible subjects were randomized to receive oral daily
      tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Baseline
      variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80;
      >=80 mL), PSA level (1.5 to <2.5; 2.5 to <4; >=4 ng/mL), age (median: <66, >=66
      years), IPSS (median: <16, >=16; IPSS thresholds, <20, >=20), IPSS QoL score
      (question 8, Q8) (median: <4, >=4), Qmax (median: <10.4, >=10.4 mL/s), BPH impact
      index (BII) (median: <5, >=5) and body mass index (BMI, median: <26.8, >=26.8
      kg/m(2) ). Within each baseline variable subgroup, changes in IPSS, Qmax and IPSS
      QoL Q8 from baseline were evaluated using a generalized linear model with effects
      for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post-baseline
      assessment up to and including the month 48 visit using a last observation
      carried forward approach. The treatment comparisons of combination therapy vs
      dutasteride and combination therapy vs tamsulosin were performed from the general
      linear model with statistical significance defined as P <= 0.01. RESULTS:
      Combination therapy resulted in a significantly greater improvement from baseline
      IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The
      benefit of combination therapy over dutasteride was confined to groups with lower
      baseline PV (<60 mL) and PSA (<4 ng/mL). In groups with baseline PV >=60 mL and
      PSA >=4 ng/mL, dutasteride and combination therapy show similar improvements in
      symptoms. Combination therapy resulted in significantly improved Qmax compared
      with tamsulosin but not dutasteride monotherapy. Qmax improvement appeared to
      increase with PV and PSA level in combination therapy subjects. The proportion of
      subjects with an IPSS QoL <=2 (at least mostly satisfied) at 48 months was
      significantly higher with combination therapy than with dutasteride for subgroups
      with PV 40-60 mL and PSA level <4 ng/mL and than with tamsulosin for all PSA
      subgroups and PV subgroups >=40 mL. CONCLUSIONS: CombAT data support the use of
      long-term combination therapy with dutasteride and tamsulosin in patients
      considered at risk for progression of BPH, as determined by high PV (>=30 mL) and
      high PSA (>=1.5 ng/mL). Combination therapy, dutasteride monotherapy and
      tamsulosin monotherapy all improved Qmax , but to different extents (combination
      therapy > dutasteride >> tamsulosin), suggesting that dutasteride contributes
      most to the Qmax benefit in combination therapy. Combination therapy provided
      consistent improvement over tamsulosin in LUTS across all analysed baseline
      variables at 48 months. Compared with dutasteride, the superiority of combination
      therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL.

PMID- 24127819
TI  - Cobalt-catalyzed diastereoselective synthesis of C-furanosides. Total synthesis
      of (-)-isoaltholactone.
AB  - An array of C-aryl and C-vinyl furanosides were prepared in good yields and
      diastereoselectivities from C-halogeno furanosides either with aryl Grignard or
      with vinyl Grignard using the convenient Co(acac)3/TMEDA catalytic system. This
      method is illustrated by the total synthesis of the (-)-isoaltholactone. 

PMID- 24127820
TI  - Acylgermanes: photoinitiators and sources for Ge-centered radicals. insights into
      their reactivity.
AB  - Acylgermanes have been shown to act as efficient photoinitiators. In this
      investigation we show how dibenzoyldiethylgermane 1 reacts upon photoexcitation.
      Our real-time investigation utilizes femto- and nanosecond transient absorption,
      time-resolved EPR (50 ns), photo-chemically induced dynamic nuclear polarization,
      DFT calculations, and GC-MS analysis. The benzoyldiethylgermyl radical G* is
      formed via the triplet state of parent 1. On the nanosecond time scale this
      radical can recombine or undergo hydrogen-transfer reactions. Radical G* reacts
      with butyl acrylate at a rate of 1.2 +/- 0.1 * 10(8) and 3.2 +/- 0.2 * 10(8) M(
      1) s(-1), in toluene and acetonitrile, respectively. This is ~1 order of
      magnitude faster than related phosphorus-based radicals. The initial germyl and
      benzoyl radicals undergo follow-up reactions leading to oligomers comprising Ge-O
      bonds. LC-NMR analysis of photocured mixtures containing 1 and the sterically
      hindered acrylate 3,3-dimethyl-2-methylenebutanoate reveals that the products
      formed in the course of a polymerization are consistent with the intermediates
      established at short time scales.

PMID- 24127821
TI  - An Outbreak of Sheep Pox in Zabajkalskij kray of Russia.
AB  - In this study, we investigated recent sheep pox outbreaks that occurred in
      Ononsky and Borzunsky regions of Zabajkalskij kray of Russia. The outbreaks
      involved in 2756 animals of which 112 were infected and 3 were slaughtered.
      Samples of injured skin of infected sheep were analysed by electron microscopy
      and CaPV-specific P32 gene amplification. Following sequence analysis of entire
      P32 gene showed that both specimens were identical to the sequence of several
      sheep poxvirus isolates from China and India. The close location of China to the
      last decade's Russian outbreaks suggest that possible future outbreaks in Russia
      could occur along the border regions with countries where sheep and goat pox are
      not controlled. 

PMID- 24127822
TI  - Anti-type VII collagen autoantibodies, detected by enzyme-linked immunosorbent
      assay, fluctuate in parallel with clinical severity in patients with
      epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering
      disease caused by autoantibodies against type VII collagen. An enzyme-linked
      immunosorbent assay (ELISA) is currently available to detect autoantibodies in
      EBA. There have been reports suggesting generically that ELISA indices reflect
      EBA disease severity; however, there is, as yet, no conclusion as to whether
      ELISA indices fluctuate with disease activity over time in each EBA patient. This
      study aimed to investigate whether ELISA titers fluctuate with EBA disease
      activity and to validate the clinical significance of checking ELISA values in
      EBA by monitoring type VII collagen ELISA titers and disease severity, evaluated
      in terms of numbers of blisters and erosions as a clinical score, over time in
      three Japanese patients with EBA. All three cases in this study, which were
      treated successfully, showed titers of anti-type VII collagen autoantibodies
      detected by ELISA that fluctuated in parallel with disease activity. Especially
      in case 1, we could determine that the expanding erosions were not due to flare
      ups of EBA because the ELISA indices stayed low, although new lesions continued
      to appear. In fact, control of infection and nutrition helped the lesions to
      become epithelialized. In conclusion, we found that repeated ELISA measurements
      are useful in monitoring disease activity and making decisions in EBA treatment
      plans. 

PMID- 24127823
TI  - Adenoviruses types, cell receptors and local innate cytokines in adenovirus
      infection.
AB  - Adenovirus is a common infectious pathogen in both children and adults. It is a
      significant cause of morbidity in immunocompetent people living in crowded living
      conditions and of mortality in immunocompromised hosts. It has more recently
      become a popular vehicle for gene therapy applications. The host response to wild
      type infection and gene therapy vector exposure involves both virus entry
      receptor and the innate immune systems. Cell-mediated recognition of viruses via
      capsid components has received significant attention, principally thought to be
      regulated by the coxsackievirus-adenovirus receptor (CAR), CD46, integrins and
      heparin sulfate-containing proteoglycans. Antiviral innate immune responses are
      initiated by the infected cell, which activates the interferon response to block
      viral replication, while simultaneously releasing chemokines to attract
      neutrophils and NK cells. This review discusses the innate immune response
      primarily during wild-type adenovirus infection because this serves as the basis
      for understanding the response during both natural infection and exposure to
      adenovirus vectors. 

PMID- 24127824
TI  - A role for Waldeyer's ring in immunological response to allergens.
AB  - OBJECTIVE: Adenoids, tubal tonsil, palatine tonsil, and lingual tonsil are
      immunological organs included in the Waldeyer's ring, the basic function of which
      is the antibody production to common environmental antigens. Adenoidal
      hypertrophy (AH) is a major medical issue in children, and adenoidectomy is still
      the most used treatment worldwide. The response of adenoids to allergens is a
      good model to evaluate their immunological function. This report assessed the
      immunological changes in adenoid tissues from children with allergic rhinitis
      (AR) undergoing sublingual immunotherapy (SLIT). METHODS: Adenoid samples from 16
      children (seven males, nine females, mean age 7.12 years) with AH and clinical
      indication to adenoidectomy were collected. Of them, five children were not
      allergic and 11 had house dust mite and grass pollen-induced AR. Among allergic
      children, in four AR was treated by antihistamines while in seven AR was treated
      by high-dose SLIT during 4-6 months. The evaluation addressed the T helper 1
      (Th1), Th2, and Th3 cells by performing a PCR array on mRNA extracted from
      adenoid samples. RESULTS: In non-allergic children, a typical Th1 pattern was
      found. SLIT induced a strong down-regulation of genes involved in Th2 and Th1
      activation and function. In particular, in SLIT-treated allergic children IL-4,
      CCR2, CCR3, and PTGDR2 (Th2 related genes) and CD28, IL-2, and INHA (Th1 related
      genes) expression was reduced, compared with children treated with
      antihistamines. CONCLUSIONS: These preliminary findings warrant investigation in
      trials including larger numbers of patients, but indicate that hypertrophic
      adenoids of allergic children have the typical response to the specific allergen
      administered by SLIT. This should suggest that one should reconsider the
      immunological role of adenoids.

PMID- 24127825
TI  - Public health significance of bipolar disorder: implications for early
      intervention and prevention.
AB  - OBJECTIVES: Early intervention and preventive strategies have become major
      targets of research and service development in psychiatry over the last few
      years. Compared to schizophrenia, bipolar disorder (BD) has received limited
      attention in this regard. In this paper, we review the available literature in
      order to explore the public health significance of BD and the extent to which
      this may justify the development of early intervention strategies for this
      disorder. METHODS: The main computerized psychiatric literature databases were
      accessed. This included Medline and PsychInfo, using the following keywords:
      bipolar, early intervention, staging model, burden, caregiver, public health, and
      manic depression. RESULTS: BD is often recurrent and has an impact that goes well
      beyond symptomatic pathology. The burden it incurs is linked not only to its
      cardinal clinical features, but also to cognitive dysfunction, poor functional
      outcome, poor physical health, high rate of comorbidities, and suicide. At a
      societal level, BD induces enormous direct and indirect costs and has a major
      impact on caregivers. The available literature reveals a usually long delay
      between illness onset and the start of treatment, and the absence of specific
      guidelines for the treatment of the early phase of BD. CONCLUSIONS: Considering
      the major impact of BD on patients and society, there is an urgent need for the
      development of early intervention strategies aimed at earlier detection and more
      specific treatment of the early phase of the disorder.

PMID- 24127826
TI  - Assessment of autism in children with visual impairment.

PMID- 24127827
TI  - Enhanced minority carrier lifetimes in GaAs/AlGaAs core-shell nanowires through
      shell growth optimization.
AB  - The effects of AlGaAs shell thickness and growth time on the minority carrier
      lifetime in the GaAs core of GaAs/AlGaAs core-shell nanowires grown by metal
      organic chemical vapor deposition are investigated. The carrier lifetime
      increases with increasing AlGaAs shell thickness up to a certain value as a
      result of reducing tunneling probability of carriers through the AlGaAs shell,
      beyond which the carrier lifetime reduces due to the diffusion of Ga-Al and/or
      impurities across the GaAs/AlGaAs heterointerface. Interdiffusion at the
      heterointerface is observed directly using high-angle annular dark field scanning
      transmission electron microscopy. We achieve room temperature minority carrier
      lifetimes of 1.9 ns by optimizing the shell growth with the intention of reducing
      the effect of interdiffusion. 

PMID- 24127828
TI  - N-acyldithieno[3,2-b:2',3'-d]pyrrole-based low-band-gap conjugated polymer solar
      cells with amine-modified [6,6]-phenyl-C61-butyric acid ester cathode
      interlayers.
AB  - Efficient low-band-gap polymers are one key component for constructing tandem
      solar cells with other higher-band-gap materials to harvest wide absorption of
      the solar spectrum. The N-acyldithieno[3,2-b:2',3'-d]pyrrole (DTP) building block
      is used for making low-band-gap polymers. It is attractive because of its strong
      donating ability and relatively low highest-occupied-molecular-orbital level in
      comparison with the N-alkyl DTP building block. However, additional solubilizing
      groups on the accepting units are needed for soluble donor-acceptor polymers
      based on the N-alkanoyl DTP building block. Combining N-benzoyl DTP with a 4,7
      dithieno-2,1,3-benzothiadiazole building block, a polymer with a low band gap of
      1.44 eV, delivers a high short-circuit current of 17.1 mA/cm(2) and a power
      conversion efficiency of 3.95%, which are the highest for the devices with DTP
      containing materials. Herein, an alcohol-soluble diamine-modified fullerene
      cathode interfacial layer improved the device efficiency significantly more than
      the mono-amine analogue. 

PMID- 24127829
TI  - Reversible chirality control in peptide-functionalized gold nanoparticles.
AB  - We report the induction of chiroptical properties in 2 nm diameter gold
      nanoparticles passivated with short peptides characterized by the Aib-l-Ala
      repetition in their sequence. The nanoparticles present relevant ECD signals in
      the 300-650 nm wavelength region, corresponding to the gold nanoparticle's
      quantized electronic structure. Although the only chiral amino acid present in
      the peptide sequences is l-Ala, the particles show mirror image spectra like
      those of enantiomers according to the number of amino acids in the main chain
      (odd or even). Such a behavior appears to be strongly influenced by the secondary
      structure assumed by the peptides when passivating the nanoparticles and vanishes
      when the sequence is long enough to assume a 310-helix conformation. Moreover,
      chirality control is a reversible process and can be deactivated or reactivated
      by increasing or decreasing the temperature. 

PMID- 24127832
TI  - Vaccination in patients with disorders of the muscle and neuromuscular junction.
AB  - Neuromuscular diseases cover a broad spectrum of conditions that have important
      differences. Infections are frequently associated with severe complications,
      mainly because the neurological involvement can cause the aspiration of
      respiratory secretions and be significantly worsened by progressive respiratory
      and/or cardiovascular disease and immunosuppressive therapy. Preventing
      infectious diseases in patients with disorders of the muscle and neuromuscular
      junction is clinically important and vaccines play an important role in this
      regard. The majority of experts recommend that patients with these disorders
      should receive the same vaccinations as those recommended for healthy subjects,
      with special attention being given to the fact that two doses of measles, mumps,
      rubella (MMR) and varicella vaccines should be administered before beginning
      immunosuppressive therapy. In addition, annual influenza vaccination and
      pneumococcal vaccination are recommended for almost all patients with disorders
      of the muscle and neuromuscular junction. 

PMID- 24127833
TI  - Dielectric barrier electrospray-polarity cycle and trigger.
AB  - The parameters influencing the combination of the dielectric barrier electrospray
      (DB-ES) with an ion trap mass spectrometer are investigated. Two approaches are
      presented: the application of different polarity cycles in the DB electrospray
      high voltage signal and the triggering of it to an output signal received by the
      mass spectrometer. Both approaches are addressed to improve the detection
      sensitivity over the sensitivity of conventional nano ES. 

PMID- 24127834
TI  - Acute outcomes after introduction of a standardized clinical assessment and
      management plan (SCAMP) for balloon aortic valvuloplasty in congenital aortic
      stenosis.
AB  - INTRODUCTION: Standardization of care can reduce practice variation, optimize
      resource utilization, and improve clinical outcomes. We have created a
      standardized clinical assessment and management plan (SCAMP) for patients having
      balloon aortic valvuloplasty (BAV) for congenital aortic stenosis (AS). This
      study compares acute outcomes of BAV at our institution before and after
      introduction of this SCAMP. METHODS: In this retrospective matched cohort study,
      each SCAMP patient was matched to four historical controls. Outcomes were
      categorized based on the combination of residual AS and aortic regurgitation (AR)
      as: (1) Optimal: gradient <= 35 mm Hg and trivial or no AR; (2) Adequate:
      gradient <= 35 mm Hg and mild AR; (3) Inadequate: gradient > 35 mm Hg and/or
      moderate or severe AR. RESULTS: All 23 SCAMP patients achieved a residual AS
      gradient <= 35 mm Hg; the median residual AS gradient for the SCAMP group was
      lower (25 [10-35] mm Hg) than in matched controls (30 [0-65] mm Hg; P = 0.005).
      The two groups did not differ with regard to degree of AR grade after BAV.
      Compared with controls, SCAMP patients were more likely to have an optimal result
      and less likely to have an inadequate result (52% vs. 34% and 17% vs. 45%,
      respectively; P = 0.02) CONCLUSIONS: A SCAMP for BAV resulted in optimal acute
      results in half of the initial 23 patients enrolled, and outcomes in this group
      were better than those of matched historical controls. Whether these improved
      acute outcomes translate into better long-term outcomes for this patient
      population remains to be seen.

PMID- 24127835
TI  - N-Hydroxycinnamide derivatives of osthole presenting genotoxicity and
      cytotoxicity against human colon adenocarcinoma cells in vitro and in vivo.
AB  - Osthole is extracted from the Chinese herbs Cnidium monnieri and Angelica
      pubescens, and it was found to have antitumor activity in vitro and in vivo. A
      series of osthole derivatives have been synthesized, and the N-hydroxycinnamide
      derivatives of osthole, WJ1376-1 and WJ1398-1 were found to have the greatest
      potential against human colon adenocarcinoma cells. In contrast to the parental
      osthole, both WJ1376-1 and WJ1398-1 were found to induce multinucleation and
      polyploidy by microscopic observation and flow cytometry. WJ1376-1 and WJ1398-1
      significantly activated ataxia telangiectasia and rad3 related (ATR) kinase,
      which triggered activation of the checkpoint kinase 2 (Chk2) signaling pathway
      and then down regulated Cdc25 phosphatase and Cdc2/cyclin B kinase activities.
      WJ1376-1 and WJ1398-1 also inhibited the phosphorylation of Aurora A kinase,
      which is associated with important processes during mitosis. The presence of a
      "comet" DNA fragment and phosphorylation of p53 at Ser 15 clearly indicated that
      DNA damage occurred with WJ1376-1 and WJ1398-1 treatment. WJ1376-1 and WJ1398-1
      ultimately induced apoptosis as evidenced by the upregulation of Bad and
      activation of caspases-3, -7, and -9. Furthermore, WJ1376-1 and WJ1398-1 also
      showed a great effect in attenuating tumor growth without affecting the body
      weight of xenograft nude mice. Taken together, these results suggest that the
      toxic activities of WJ1376-1 and WJ1398-1 were dissimilar to that of the parental
      osthole, which can induce cell polyploidy and G2/M cell cycle arrest in colon
      adenocarcinoma cells and may provide a potential therapeutic target for colon
      cancer treatment in the future. 

PMID- 24127836
TI  - Application of D-optimal experimental design method to optimize the formulation
      of O/W cosmetic emulsions.
AB  - OBJECTIVE: This study investigates the application of D-optimal mixture
      experimental design in optimization of O/W cosmetic emulsions. Cetearyl glucoside
      was used as a natural, biodegradable non-ionic emulsifier in the relatively low
      concentration (1%), and the mixture of co-emulsifiers (stearic acid, cetyl
      alcohol, stearyl alcohol and glyceryl stearate) was used to stabilize the
      formulations. METHODS: To determine the optimal composition of co-emulsifiers
      mixture, D-optimal mixture experimental design was used. Prepared emulsions were
      characterized with rheological measurements, centrifugation test, specific
      conductivity and pH value measurements. RESULTS: All prepared samples appeared as
      white and homogenous creams, except for one homogenous and viscous lotion co
      stabilized by stearic acid alone. Centrifugation testing revealed some phase
      separation only in the case of sample co-stabilized using glyceryl stearate
      alone. The obtained pH values indicated that all samples expressed mild acid
      value acceptable for cosmetic preparations. Specific conductivity values are
      attributed to the multiple phases O/W emulsions with high percentages of fixed
      water. Results of the rheological measurements have shown that the investigated
      samples exhibited non-Newtonian thixotropic behaviour. To determine the influence
      of each of the co-emulsifiers on emulsions properties, the obtained results were
      evaluated by the means of statistical analysis (ANOVA test). On the basis of
      comparison of statistical parameters for each of the studied responses, mixture
      reduced quadratic model was selected over the linear model implying that
      interactions between co-emulsifiers play the significant role in overall
      influence of co-emulsifiers on emulsions properties. CONCLUSION: Glyceryl
      stearate was found to be the dominant co-emulsifier affecting emulsions
      properties. Interactions between the glyceryl stearate and other co-emulsifiers
      were also found to significantly influence emulsions properties. These findings
      are especially important as they can be used for development of the product that
      meets users' requirements, as represented in the study.

PMID- 24127837
TI  - The Aeromonas salmonicida subsp. salmonicida exoproteome: global analysis,
      moonlighting proteins and putative antigens for vaccination against furunculosis.
AB  - BACKGROUND: Aeromonas salmonicida subsp. salmonicida, the etiologic agent of
      furunculosis, is a major pathogen of fisheries worldwide. Despite the
      identification of several virulence factors the pathogenesis is still poorly
      understood. We have used high-throughput proteomics to display the differences
      between in vitro secretome of A. salmonicida wild-type (wt, hypervirulent,
      JF5054) and T3SS-deficient (isogenic DeltaascV, extremely low-virulent, JF2747)
      strains in exponential (GP) and stationary (SP) phases of growth. RESULTS: Among
      the different experimental conditions we obtained semi-quantitative values for a
      total of 2136 A. salmonicida proteins. Proteins of specific A. salmonicida
      species were proportionally less detected than proteins common to the Aeromonas
      genus or those shared with other Aeromonas species, suggesting that in vitro
      growth did not induce the expression of these genes. Four detected proteins which
      are unidentified in the genome of reference strains of A. salmonicida were
      homologous to components of the conjugative T4SS of A. hydrophila pRA1 plasmid.
      Polypeptides of three proteins which are specific to the 01-B526 strain were also
      discovered. In supernatants (SNs), the number of detected proteins was higher in
      SP (326 for wt vs 329 for mutant) than in GP (275 for wt vs 263 for mutant). In
      pellets, the number of identified proteins (a total of 1536) was approximately
      the same between GP and SP. Numerous highly conserved cytoplasmic proteins were
      present in A. salmonicida SNs (mainly EF-Tu, EF-G, EF-P, EF-Ts, TypA, AlaS,
      ribosomal proteins, HtpG, DnaK, peptidyl-prolyl cis-trans isomerases, GAPDH,
      Enolase, FbaA, TpiA, Pgk, TktA, AckA, AcnB, Mdh, AhpC, Tpx, SodB and PNPase), and
      several evidences support the theory that their extracellular localization was
      not the result of cell lysis. According to the Cluster of Orthologous Groups
      classification, 29% of excreted proteins in A. salmonicida SNs were currently
      poorly characterized. CONCLUSIONS: In this part of our work we elucidated the
      whole in vitro exoproteome of hypervirulent A. salmonicida subsp. salmonicida and
      showed the secretion of several highly conserved cytoplasmic proteins with
      putative moonlighting functions and roles in virulence. All together, our results
      offer new information about the pathogenesis of furunculosis and point out
      potential candidates for vaccine development.

PMID- 24127838
TI  - Penile vibratory stimulation in the recovery of urinary continence and erectile
      function after nerve-sparing radical prostatectomy: a randomized, controlled
      trial.
AB  - OBJECTIVE: To examine the effect of penile vibratory stimulation (PVS) in the
      preservation and restoration of erectile function and urinary continence in
      conjunction with nerve-sparing radical prostatectomy (RP). PATIENTS AND METHODS:
      The present study was conducted between July 2010 and March 2013 as a randomized
      prospective trial at two university hospitals. Eligible participants were
      continent men with an International Index of Erectile Function-5 (IIEF-5) score
      of at least 18, scheduled to undergo nerve-sparing RP. Patients were randomized
      to a PVS group or a control group. Patients in the PVS group were instructed in
      using a PVS device (FERTI CARE((r)) vibrator). Stimulation was performed at the
      frenulum once daily by the patients in their own homes for at least 1 week before
      surgery. After catheter removal, daily PVS was re-initiated for a period of 6
      weeks. Participants were evaluated at 3, 6 and 12 months after surgery with the
      IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to
      one pad daily for security reasons only were considered continent. The study was
      registered at http://clinicaltrials.gov/ (NCT01067261). RESULTS: Data from 68
      patients were available for analyses (30 patients randomized to PVS and 38
      patients randomized to the control group). The IIEF-5 score was highest in the
      PVS group at all time points after surgery with a median score of 18 vs 7.5 in
      the control group at 12 months (P = 0.09), but the difference only reached
      borderline significance. At 12 months, 16/30 (53%) patients in the PVS group had
      reached an IIEF-5 score of at least 18, while this was the case for 12/38 (32%)
      patients in the control group (P = 0.07). There were no significant differences
      in the proportions of continent patients between groups at 3, 6 or 12 months. At
      12 months 90% of the PVS patients were continent, while 94.7% of the control
      patients were continent (P = 0.46). CONCLUSION: The present study did not
      document a significant effect of PVS. However, the method proved to be acceptable
      for most patients and there was a trend towards better erectile function with
      PVS. More studies are needed to explore this possible effect further.

PMID- 24127839
TI  - 'Naked' and hydrated conformers of the conserved core pentasaccharide of N-linked
      glycoproteins and its building blocks.
AB  - N-glycosylation of eukaryotic proteins is widespread and vital to survival. The
      pentasaccharide unit -Man3GlcNAc2- lies at the protein-junction core of all
      oligosaccharides attached to asparagine side chains during this process. Although
      its absolute conservation implies an indispensable role, associated perhaps with
      its structure, its unbiased conformation and the potential modulating role of
      solvation are unknown; both have now been explored through a combination of
      synthesis, laser spectroscopy, and computation. The proximal -GlcNAc-GlcNAc- unit
      acts as a rigid rod, while the central, and unusual, -Man-beta-1,4-GlcNAc-
      linkage is more flexible and is modulated by the distal Man-alpha-1,3- and Man
      alpha-1,6- branching units. Solvation stiffens the 'rod' but leaves the distal
      residues flexible, through a beta-Man pivot, ensuring anchored projection from
      the protein shell while allowing flexible interaction of the distal portion of N
      glycosylation with bulk water and biomolecular assemblies. 

PMID- 24127840
TI  - Coxiella burnetii Shedding by Farmed Red Deer (Cervus elaphus).
AB  - Wildlife and notably deer species--due to the increasing relevance of deer
      farming worldwide--may contribute to the maintenance of Coxiella burnetii, the
      causal agent of Q fever. Currently, there are no precedents linking exposure to
      deer species with human Q fever cases. However, a human case of Q fever was
      recently diagnosed in a red deer (Cervus elaphus) farm, which led us to
      investigate whether deer could be a source for environmental contamination with
      C. burnetii and ascertain the implication of C. burnetii in reproductive failure
      in the farm. Blood serum and vaginal swabs were collected from hinds either
      experiencing or not reproductive failure and tested to detect the presence of
      antibodies and DNA, respectively, of C. burnetii, Chlamydia abortus, Neospora
      caninum and Toxoplasma gondii. Serology and PCR results suggest C. burnetii was
      the primary cause of the reproductive failure. We identified vaginal shedding of
      C. burnetii in hinds, confirming red deer as a source of Q fever zoonotic
      infection.

PMID- 24127841
TI  - Rhodium-catalyzed decarboxylative and dehydrogenative coupling of maleic acids
      with alkynes and alkenes.
AB  - The dehydrogenative coupling of maleic acids with alkynes proceeds smoothly
      accompanied by decarboxylation under rhodium catalysis to produce variously
      substituted alpha-pyrone derivatives. The catalyst system is also applicable to
      the coupling with 1,3-diynes and alkenes. 

PMID- 24127842
TI  - Reactive hyperaemia index as a marker of endothelial dysfunction in children with
      Crohn's disease is significantly lower than healthy controls.
AB  - AIM: Patients with inflammatory bowel disease (IBD) are prone to cardiovascular
      disorders, although there is little research to support this assertion, and other
      data are controversial in children. We aimed to determine the extent of premature
      atherosclerosis in Crohn's disease (CD) by measuring reactive hyperaemia index
      (RHI) as a functional marker of endothelial dysfunction (ED). METHODS: Twenty-one
      patients with CD and twelve healthy matched subjects were enrolled in the study.
      Diagnosis was based on the standard clinical, endoscopic and histological
      criteria, including the Paediatric Crohn's disease Activity Index. ED was
      assessed using the plethysmographic RHI, combined with specific biochemical
      markers of ED. RESULT: RHI values were significantly lower in the patients with
      CD than the controls (p < 0.05). E-selectin (p < 0.05), asymmetric
      dimethylarginine (p < 0.01) and high-sensitive CRP (p < 0.05), but not vascular
      cells adhesive molecule-1 values, were significantly increased in the CD subjects
      compared with the control group. CONCLUSION: Significantly decreased RHI and
      elevated plasma levels of specific biochemical parameters seems to be related to
      systemic inflammation and ED in children with CD. Our results support the
      hypothesis regarding RHI and ED in paediatric CD. This combined method assessment
      might be a useful tool for detection of ED and stratification of cardiovascular
      risk in patients with CD.

PMID- 24127843
TI  - Adherence to physical activity guidelines among cancer support group
      participants.
AB  - Physical activity is recommended after cancer diagnosis for physical function,
      quality of life and survival benefits. This study provided preliminary data on
      the prevalence of physical activity among adult men and women with cancer in the
      UK. As part of a national survey of cancer support group participation,
      questionnaires including items on leisure-time physical activity and demographic
      information were completed by 748 cancer survivors. Overall, 395 (52.8%)
      participants reported no weekly moderate or vigorous intensity physical activity,
      221 (29.5%) reported some activity but below minimum recommendations and 132
      (17.6%) were meeting published guidelines. Gender, health status and socio
      economic status were independently associated with meeting guidelines. Among
      participants in good or fair health who were not meeting guidelines, 59.9%
      thought that they ought to be more physically active. In conclusion, overall
      levels of physical activity are low among cancer survivors in the UK. However,
      the majority of insufficiently active participants showed awareness of the need
      to increase their activity, and may be receptive to interventions for promoting
      physical activity in this population. 

PMID- 24127844
TI  - Targeting histidine side chains in molecular design through nitrogen-halogen
      bonds.
AB  - Halogen bonds are directional noncovalent interactions that can be used to target
      electron donors in a protein binding site. In this study, we employ quantum
      chemical calculations to explore halogen...nitrogen contacts involving histidine
      side chains. We characterize the energetics on the MP2 level of theory using SCS
      MP2 and CCSD(T)/CBS as reference calculations and elucidate their energy profile
      in suboptimal geometries. We derive simple rules allowing medicinal chemists and
      chemical biologists to easily determine preferred areas of interaction in a
      binding site and exploit them for scaffold decoration and design. Our work shows
      that nitrogen-halogen bonds are valuable interactions that are this far
      underexploited in patent applications, lead structure, and clinical candidate
      selection. We highlight their potential to increase binding affinities and
      suggest that they can significantly contribute to inducing and tuning subtype
      selectivities. 

PMID- 24127846
TI  - Late preterm birth is associated with short-term morbidity but not with adverse
      neurodevelopmental and physical outcomes at 1 year.
AB  - We compared the neonatal and infant outcomes at one year (Bayley mental and
      psychomotor development index, and physical growth) of babies who were (n = 63)
      or were not (n = 100) delivered prior to 37 weeks in women admitted in threatened
      late preterm labor (34-35(+6) weeks) with a cervix <=15 mm. The women were part
      of a clinical trial to investigate the tocolytic effect of the oxytocin
      antagonist barusiban. Babies born late preterm (34-36(+6) weeks) had a
      significantly increased risk of short-term morbidity (hepatobiliary disorders,
      respiratory disorders, metabolic disorders, nervous system disorders, infection;
      p < 0.05 for each) compared with those born at term, but there were no
      significant differences in the neurodevelopmental and physical outcomes at one
      year (p > 0.05 for both one-year outcomes).

PMID- 24127847
TI  - Layer-by-layer fabrication of oriented porous thin films based on porphyrin
      containing metal-organic frameworks.
AB  - We report the synthesis and characterization of two thin films (DA-MOF and L2
      MOF) of porphyrin-based MOFs on functionalized surfaces using a layer-by-layer
      (LbL) approach. Profilometry measurements confirm that the film thickness
      increases systematically with number of growth cycles. Polarization excitation
      and fluorescence measurements indicate that the porphyrin units are
      preferentially oriented, while X-ray reflectivity scans point to periodic
      ordering. Ellipsometry measurements show that the films are highly porous. Since
      there are currently few methods capable of yielding microporous MOFs containing
      accessible free-base porphyrins, it is noteworthy that the LbL growth permits
      direct MOF incorporation of unmetalated porphyrins. Long-range energy transfer is
      demonstrated for both MOF films. The findings offer useful insights for
      subsequent fabrication of MOF-based solar energy conversion devices. 

PMID- 24127845
TI  - Immunosenescence and immune response in organ transplantation.
AB  - The immune system undergoes a complex and continuous remodeling with aging.
      Immunosenescence results into both quantitative and qualitative changes of
      specific cellular subpopulations that have major impact on allorecognition and
      alloresponse, and consequently on graft rejection and tolerance. Here, we are
      going to review the immunological changes associated with the aging process
      relevant for transplantation. Interventions to selectively target changes
      associated with the senescence process seem promising therapeutic strategies to
      improve transplantation outcome. 

PMID- 24127848
TI  - Antibiotic drugs aminoglycosides cleave DNA at abasic sites: shedding new light
      on their toxicity?
AB  - Abasic sites are probably the most common lesions in DNA resulting from the
      hydrolytic cleavage of glycosidic bonds that can occur spontaneously and through
      DNA alkylation by anticancer agents, by radiotherapy, and during the repair
      processes of damaged nucleic bases. If not repaired, the abasic site can be
      mutagenic or lethal. Thus, compounds able to specifically bind and react at
      abasic sites have attracted much attention for therapeutic and diagnostic
      purposes. Here, we report on the efficient cleavage activity of characteristic
      antibiotic drugs of the major aminoglycosides (AG) family at abasic sites
      introduced either by depurination in a plasmidic DNA or site specifically in a
      synthetic oligonucleotide. Among the antibiotic AG drugs selected for this study,
      neomycin B is the most efficient (a 0.1 MUM concentration induces 50% cleavage of
      an abasic site containing DNA). This cleavage activity could be related to
      aminoglycoside toxicity but also find medicinal applications through potentiation
      of cancer radiotherapy and chemotherapy with alkylating drugs. In the search for
      antibiotic and antiviral agents, we have previously described the synthesis of
      derivatives of the small aminoglycoside neamine, which corresponds to rings I and
      II of neomycin B constituted of four rings. The cleavage activity at abasic sites
      of four of these neamine derivatives is also reported in the present study. One
      of them appeared to be much more active than the parent compound neamine with
      cleavage efficiency close to that of neomycin. 

PMID- 24127849
TI  - Case of congenital dermatofibrosarcoma protuberans: change of clinical features
      and pathological findings over 10 years.

PMID- 24127850
TI  - Mobilizing and evaluating anticancer T cells: pitfalls and solutions.
AB  - Immunotherapy is a promising means to fight cancer, prompting a steady increase
      in clinical trials and correlative laboratory studies in this field. As antitumor
      T cells play central roles in immunity against malignant diseases, most
      immunotherapeutic protocols aim to induce and/or strengthen their function.
      Various treatment strategies have elicited encouraging clinical responses;
      however, major challenges have been uncovered that should be addressed in order
      to fully exploit the potential of immunotherapy. Here, we outline pitfalls for
      the mobilization of antitumor T cells and offer solutions to improve their
      therapeutic efficacy. We provide a critical perspective on the main methodologies
      used to characterize T-cell responses to cancer therapies, with a focus on
      discrepancies between T-cell attributes measured in vitro and protective
      responses in vivo. This review altogether provides recommendations to optimize
      the design of future clinical trials and highlights important considerations for
      the proficient analysis of clinical specimens available for research. 

PMID- 24127851
TI  - Are prophylactic antibiotics necessary in patients with preoperative sterile
      urine undergoing ureterorenoscopic lithotripsy?
AB  - OBJECTIVE: To compare the efficacy of prophylactic antibiotics in reducing post
      surgical infections in patients undergoing ureterorenoscopic lithotripsy (URSL).
      PATIENTS AND METHODS: The study was a double-blind, prospective, randomized
      controlled trial. Between 2009 and 2012, 212 patients with preoperative sterile
      urine undergoing URSL were randomly allocated, in a ratio of 1:1:1:1, to receive
      prophylactic antibiotics with single-dose i.v. cefazolin (1 g), ceftriaxone (1 g)
      or oral levofloxacin (500 mg), or no treatment (control group), respectively.
      Urine analysis and urine cultures were obtained between postoperative days 5 and
      7. Pyuria was defined as >=10 white blood cells/high power field. Significant
      bacteriuria was defined as >=100,000 colony-forming units uropathogens/mL.
      Febrile urinary tract infection (fUTI) was defined as a body temperature of 38.5 
      degrees C with pyuria or significant bacteriuria <=7 days after surgery. RESULTS:
      In total, 206 patients were eligible for analysis. The rates of postoperative
      pyuria were significantly lower in patients with prophylaxis than in the control
      group (48.4 vs 64.7%, P = 0.04). Patients receiving prophylaxis with levofloxacin
      and ceftriaxone had a significantly lower risk of pyuria compared with the
      control group (52.0 and 36.5 vs 64.7%, respectively; P < 0.05). The rates of
      bacteriuria and fUTI tended to be lower in patients with prophylaxis, although
      the difference was not significant (4.5 vs 11.8%, P = 0.09, 1.3 vs 5.9%, P =
      0.09). There was no significant difference in rates of bacteriuria and fUTI
      between the four groups. Patients with proximal stones had a higher risk of
      developing postoperative fUTI (odds ratio 9.35; P = 0.03). CONCLUSION: Antibiotic
      prophylaxis significantly reduces the incidence of pyuria after URSL and tends to
      diminish the risk of bacteriuria and fUTI.

PMID- 24127852
TI  - A low-marker density implementation of genomic selection in aquaculture using
      within-family genomic breeding values.
AB  - BACKGROUND: Genomic selection can increase genetic gain within aquaculture
      breeding programs, but the high costs related to high-density genotyping of a
      large number of individuals would make the breeding program expensive. In this
      study, a low-cost method using low-density genotyping of pre-selected candidates
      and their sibs was evaluated by stochastic simulation. METHODS: A breeding scheme
      with selection for two traits, one measured on candidates and one on sibs was
      simulated. Genomic breeding values were estimated within families and combined
      with conventional family breeding values for candidates that were pre-selected
      based on conventional BLUP breeding values. This strategy was compared with a
      conventional breeding scheme and a full genomic selection program for which
      genomic breeding values were estimated across the whole population. The effects
      of marker density, level of pre-selection and number of sibs tested and genotyped
      for the sib-trait were studied. RESULTS: Within-family genomic breeding values
      increased genetic gain by 15% and reduced rate of inbreeding by 15%. Genetic gain
      was robust to a reduction in marker density, with only moderate reductions, even
      for very low densities. Pre-selection of candidates down to approximately 10% of
      the candidates before genotyping also had minor effects on genetic gain, but
      depended somewhat on marker density. The number of test-individuals, i.e.
      individuals tested for the sib-trait, affected genetic gain, but the fraction of
      the test-individuals genotyped only affected the relative contribution of each
      trait to genetic gain. CONCLUSIONS: A combination of genomic within-family
      breeding values, based on low-density genotyping, and conventional BLUP family
      breeding values was shown to be a possible low marker density implementation of
      genomic selection for species with large full-sib families for which the costs of
      genotyping must be kept low without compromising the effect of genomic selection
      on genetic gain.

PMID- 24127853
TI  - A prospective study of diagnostic conversion of major depressive disorder to
      bipolar disorder in pregnancy and postpartum.
AB  - OBJECTIVES: The aim of the present study was to determine the rate of, and risk
      factors for, a change in diagnosis from major depressive disorder to bipolar
      disorder, and from bipolar II disorder to bipolar I disorder in pregnancy and
      postpartum. METHODS: Patients with a prior history of major depressive disorder
      or bipolar II disorder were recruited between 24 and 28 weeks' gestation and
      followed through to one year postpartum. Diagnostic interviews were conducted
      using the Structured Clinical Interview for DSM-IV at study intake and repeated
      using the Mini-International Psychiatric Interview at one, three, six, and 12
      months after childbirth. Fisher's exact test was used to assess the association
      between various risk factors and diagnostic switch. RESULTS: A total of 146
      participants completed the intake interview and at least one follow-up interview
      postpartum. Of these, 92 were diagnosed with major depressive disorder and 54
      with bipolar II disorder at intake. Six women (6.52%) experienced a diagnostic
      change from major depressive disorder to bipolar II disorder during the first six
      months after childbirth. There were no cases of switching to bipolar I disorder,
      but in one participant the diagnosis changed from bipolar II disorder to bipolar
      I disorder during the three months after childbirth. Bipolar switch was
      associated with a family history of bipolar disorder. CONCLUSIONS: The postpartum
      period appears to be a time of high risk for a new onset of hypomania in women
      with major depressive disorder. Our rate of diagnostic switching to bipolar II
      disorder (6.52%) is at least 11- to 18-fold higher than the rates of switching in
      similar studies conducted in both men and women.

PMID- 24127854
TI  - pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica
      nanoparticles encapsulated in a copolymer-lipid bilayer.
AB  - A pH and thermo dual-controllable composite structure was developed as a
      triggerable drug delivery carrier. In such a drug carrier, a mesoporous silica
      nanoparticle (MSN) acts as the drug loading core, while a layer of copolymer
      lipid serves as the dual-responsive gating shell. Specifically, the copolymer
      lipid bilayer consists of natural phospholipids (soy phosphatidylcholine, SPC)
      and the poly(N-isopropylacrylamide-methacrylic acid-octadecyl acrylate) (p(NIPAM
      MAA-ODA)) copolymer. With this structure, a high drug loading capacity and a
      sustained release effect could be provided by the MSN core, while a pH and thermo
      dual-responsive releasing ability could be offered by the copolymer-lipid
      bilayer. In addition, the introduction of SPC instead of the traditionally used
      phospholipids (such as dioleoyl phosphatidylethanolamine (DOPE) or dipalmitoyl
      phosphatidylcholine (DPPC)) results in a much lower cost and a better serum
      stability. Using doxorubicin (DOX) as the drug model, our results confirmed that
      either pH or temperature can trigger the drug release. However, much more drugs
      could be released by simultaneously controlling the pH and temperature.
      Furthermore, after being cocultured with cancer cells (MCF-7), the drug carriers
      transported DOX into the cells and exhibited a pH-sensitive release behavior.
      Since most tumor sites usually exhibit a more acidic environment or a higher
      temperature, the pH- and thermo-responsive releasing ability of this drug carrier
      is particularly useful and important for the targeted release at the tumor
      region. Thus, due to the powerful controlled releasing ability, the
      straightforward preparation method, and low cost, the demonstrated nanocarrier
      will have potential applications in controllable drug delivery and cancer
      therapy. 

PMID- 24127855
TI  - Compact aperiodic metallic groove arrays for unidirectional launching of surface
      plasmons.
AB  - The ever-increasing power of computers and the development of new optimization
      methodologies have enabled the ability to design complex aperiodic devices, which
      can outperform periodic ones and offer new functionalities. Here, we describe the
      realization of an ultracompact aperiodic grating coupler capable of selectively
      launching surface plasmon polaritons (SPPs) in a desired direction. We use a
      transfer matrix model to facilitate the rapid optimization of such structures. We
      demonstrate both numerically and experimentally that a structure consisting of
      five subwavelength grooves patterned into silver can unidirectionally launch SPPs
      in the visible spectral range with a record right-to-left contrast ratio of 55.
      The general design principles behind this study can readily be extended to a
      great diversity of sophisticated aperiodic nanophotonic structures. 

PMID- 24127856
TI  - N-methyl-D-aspartate receptor antibody-associated movement disorder without
      encephalopathy.
AB  - N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is a well-recognized
      clinico-immunological syndrome that presents with a movement disorder, cognitive
      decline, psychiatric symptoms, and epileptic seizures. A pure monosymptomatic
      presentation is rare; however, some patients present predominantly with a
      movement disorder in the absence of encephalopathy. Here, we describe three
      paediatric patients with an NMDAR antibody-mediated movement disorder: a 5-year
      old female with acute onset hemichorea, a 10-year-old female with generalized
      chorea, and a 12-year-old male with abdominal myoclonus. These patients did not
      develop the characteristic encephalopathy syndrome seen in NMDAR encephalitis,
      but all three had other associated subtle cognitive deficits. The patients
      demonstrated good responses to immunotherapy. 

PMID- 24127857
TI  - Prevalence of MRSA colonization in Japanese neonatal care unit patients in 2011.
AB  - BACKGROUND: The neonatal intensive care unit (NICU) is a high-risk setting for
      transmission of methicillin-resistant Staphylococcus aureus (MRSA). The recent
      prevalence of colonization with MRSA in patients and its control measures are
      unknown in Japanese NICU. We investigated the prevalence of MRSA colonization in
      patients and measures to control and prevent health-care-associated transmission
      in Japanese NICU in 2011. METHODS: A nationwide survey was performed in
      facilities certified as training hospitals for neonatologists. Data in NICU and
      growing care units (GCU) were collected and analyzed regarding surveillance
      cultures for MRSA and the proportion of MRSA-colonized patients in September
      2011. Trends in the proportion of MRSA-colonized patients and the measures to
      control and prevent health-care-associated MRSA transmission were investigated in
      the surveyed NICU in 2000, 2003, and 2011. RESULTS: A total of 168 NICU and 158
      GCU were analyzed. The proportions of NICU and GCU that conducted regular
      surveillance cultures for MRSA were 81% and 66%, respectively. MRSA colonization
      was not found in 53% of NICU and in 45% of GCU. The percentage of NICU reported
      to be free of MRSA colonization increased over time. Use of alcohol-based hand
      rub and gloves by clinical staff and cohorting for identified MRSA-positive
      patients became more common in 2011 than in 2000 or 2003. CONCLUSIONS:
      Approximately half of Japanese NICU did not observe any patients with MRSA
      colonization in September 2011. Control and prevention measures have changed to
      use of alcohol-based hand rub and gloves in the last decade.

PMID- 24127858
TI  - Synthesis of C-glycosyl pyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as a scaffold
      for check point kinase 1 inhibitors.
AB  - Indolocarbazole natural products are known to possess a variety of biological
      activities that hold promise as cancer chemotherapeutic agents. We newly designed
      C-glycosyl pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione derivatives 7 and 8, which
      are natural-product-like scaffolds. Compounds 7 and 8 were stereoselectively and
      efficiently synthesized using beta-selective C-allylation, Heck reaction, and
      thermal 6pi-electron cyclization/oxidative aromatization. Their potential as Chk1
      inhibitors was investigated, and 7 and 8 exhibited an inhibitory activity with
      IC50 values of 0.5-9.5 MUM, which is good activity for scaffolds. The key
      intermediate 23 was obtained by five steps from d-ribose in 33% overall yield by
      this synthetic route, which would enable us to prepare a range of analogues in
      order to investigate further structure-activity relationship studies in the
      optimization process. 

PMID- 24127859
TI  - The 2014 Danish references from birth to 20 years for height, weight and body
      mass index.
AB  - AIM: To construct new Danish growth charts for 0- to 20-year-olds and to compare
      them with Danish references from 1982 and with World Health Organization (WHO)
      standards for children aged 0-5 years from 2006, by applying similar inclusion
      and exclusion criteria. METHODS: Anthropometric data from three contemporary
      Danish population-based studies were combined. References for height were based
      on healthy Caucasian children born at term. A total of 12,671 height measurements
      (8055 in boys and 4616 in girls) were included. Reference charts were developed
      using the generalised additive models for location, scale and shape. RESULTS:
      From prepubertal ages, a secular increase in height was observed for both
      genders. The differences were most pronounced in puberty, and final heights were
      increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In
      boys, but not girls an upward shift in body mass index (BMI) above median levels
      was found. Reference curves for height were superimposable with standard curves
      based on the selective WHO criteria. Danish children were longer/taller and
      heavier and they had larger head circumferences than those reported in the recent
      multiethnic WHO standards. CONCLUSION: We recommend national implementation of
      these contemporary 2014 Danish references for anthropometric measurements.

PMID- 24127860
TI  - Primary medulla oblongata germinomas: two case reports and review of the
      literature.
AB  - An intracranial germinoma is a tumor that is sensitive to radiotherapy. As
      medulla oblongata germinomas are extremely rare, determining an accurate
      preoperative diagnosis is challenging. Two cases of medulla oblongata lesions
      were surgically treated, and a postoperative diagnosis of germinoma was
      determined in both of the cases. The tumor in one patient completely resolved
      after a treatment course consisting of surgical intervention, radiotherapy and
      chemotherapy; the other patient, who did not receive any type of adjuvant
      treatment after surgery, suffered from tumor relapse and died from pneumonia 8
      months following surgery. A preoperative diagnosis of medulla oblongata germinoma
      is difficult because of the lack of specific clinical signs and symptoms. If the
      correct diagnosis is reached, patients can have a favorable prognosis with proper
      evaluation and treatment. An invasive operation can potentially lesion and impair
      the function of the medulla oblongata, which is fatal to the patient.

PMID- 24127861
TI  - Management of patent ductus arteriosus in preterm infants--where do we stand?
AB  - Patent ductus arteriosus (PDA) in preterm infants is a controversial topic in the
      management of preterm neonates. There are no generally accepted guidelines for
      diagnosis, treatment, and follow-up of PDA, and few publications have covered the
      whole topic or have been conclusively summarized to give a proper direction for
      the treating physician. Major issues remain to be clarified, both with respect to
      diagnosis and treatment. The definition of hemodynamic significance varies
      because of different use of echocardiographic criteria and uncertainty about the
      role of biomarkers. The detailed risks and benefits of available treatment
      alternatives are still under investigation. There has been a general shift in the
      management of PDA in preterm neonates from the "aggressive approach" to a more
      "conservative approach," but the effects of this strategy on morbidity in a
      longer time perspective are not fully known. An individualized therapeutic
      strategy with special emphasis on identification of hemodynamically significance
      seems to be the way forward. In this review we put forward the scientific
      background in favor of a seemingly growing body of evidence against active
      treatment, but we raise caution against shying away from all forms of treatment
      or instituting them too late. Finally, we try to integrate the current knowledge
      into suggestions for the management of PDA in premature infants. 

PMID- 24127862
TI  - Proceedings from the 9th Annual Meeting of International Society for Medical
      Publication Professionals Roundtable Session: key insights.
AB  - INTRODUCTION: During the 9th Annual Meeting of the International Society for
      Medical Publication Professionals (ISMPP, April 29-May 1, 2013 in Baltimore, MD),
      ~650 participants attended two of 13 available roundtable sessions. Participants
      included medical publication professionals from industry, communication agencies,
      and journals. DISCUSSION TOPICS: Roundtable participants discussed how to best
      interpret and implement various guidances, such as Good Publication Practices 2
      (GPP2), the International Committee of Medical Journal Editors (ICMJE)
      guidelines, and the Physician Payment Sunshine Act. The impact of and compliance
      with Corporate Integrity agreements (CIAs) on medical publication planning
      practices was debated. Roundtable participants also discussed ways of advancing
      both advocacy for the medical publication professional field and internal and
      external collaborations. The development of review manuscripts, publications from
      regions newly emerging in publication planning, medical devices publications, and
      real-world experience publications were discussed. Participants also considered
      the benefits and uncertainties of new technologies in medical publications such
      as multimedia and social media. SUMMARY: This is the first ever article to be
      published following the well-attended ISMPP roundtable sessions. The objective of
      this manuscript is to summarize key learnings that will aid continued discussions
      about challenges and opportunities facing medical publication professionals.

PMID- 24127865
TI  - Shape and size controlled synthesis of MOF nanocrystals with the assistance of
      ionic liquid mircoemulsions.
AB  - In this work, the La-metal-organic frameworks (La-MOFs) were synthesized using
      lanthanum(III) nitrate and 1,3,5-benzenetricarboxylic acid (BTC) in H2O-in-1
      butyl-3-methylimidazolium hexafluorophosphate (bmimPF6), bmimPF6-in-water, and
      the bicontinuous microemulsions stabilized by surfactant TX-100. The MOFs
      prepared were characterized by scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), powder X-ray diffraction (XRD), thermal gravimetric
      analysis (TGA), and FT-IR methods, and the microstructures of the microemulsions
      in the H2O/bmimPF6/TX-100 system were studied by small-angle X-ray scattering
      (SXAS) technique. It was shown that the dispersed droplets in the water-in
      bmimPF6, bicontinuous and bmimPF6-in-water microemulsions were spherical,
      lamellar, and cylindrical, respectively. The shapes of the La-MOFs synthesized
      were similar to that of the droplets in the corresponding microemulsions. This
      indicated that the morphology of MOFs could be controlled by the microstructures
      of the microemulsions. On the basis of the systematic experimental results, the
      mechanism for controlling the morphology of the MOFs was proposed. 

PMID- 24127863
TI  - Glycosyltransferases and glycosaminoglycans in bleomycin and transforming growth
      factor-beta1-induced pulmonary fibrosis.
AB  - Glycosaminoglycan (GAG) chains of proteoglycans (PGs) play important roles in
      fibrosis through cell-matrix interactions and growth factor binding in the
      extracellular matrix. We investigated the expression and regulation of PG core
      protein (versican) and key enzymes (xylosyltransferase [XT]-I, beta1,3
      glucuronosyltransferase [GlcAT]-I, chondroitin-4-sulfotransferase [C4ST])
      implicated in synthesis and sulfation of GAGs in bleomycin (BLM) and adenovirus
      transforming growth factor (TGF)-beta1-induced lung fibrosis in rats. We also
      studied the role of GlcAT-I or TGF-beta1 and the signaling pathways regulating PG
      GAG production in primary lung fibroblasts isolated from saline- or BLM-instilled
      rats. The mRNA for XT-I, GlcAT-I, C4ST, and versican was increased in the lung 14
      days after BLM injury. In vitro studies indicate that fibrotic lung fibroblasts
      (FLFs) expressed more XT-I, C4ST, and chondroitin sulfate (CS)-GAGs than did
      normal lung fibroblasts at baseline. TGF-beta1 enhanced the expression of XT-I,
      C4ST-I, and versican in normal lung fibroblasts, whereas SB203580 or SB431542, by
      targeting p38 mitogen-activated protein kinase or TGF-beta type-1
      receptor/activin receptor-like kinase 5, respectively, attenuated the response to
      both TGF-beta1 and FLFs on PG-GAG expression. Neutralizing anti-TGF-beta1
      antibody abrogated FLF-conditioned medium-stimulated expression of XT-I, GlcAT-I,
      versican, and CS-GAG. Forced expression of TGF-beta1 in vivo enhanced versican,
      XT-I, GlcAT-I, and C4ST-I expression and PG-GAG deposition in rat lungs. Finally,
      induced expression of GlcAT-I gene in rat lung fibroblasts increased GAG
      synthesis by these cells. Together, our results provide new insights into the
      basis for increased PG-GAG deposition in lung fibrosis; inhibition of TGF-beta1
      mediated or fibrosis-induced PG-GAG production by activin receptor-like kinase
      5/p38 inhibitors may contribute to antifibrotic activity. 

PMID- 24127866
TI  - MyD88 knockout mice develop initial enlarged periapical lesions with increased
      numbers of neutrophils.
AB  - AIM: To characterize the formation and progression of experimentally induced
      periapical lesions in teeth of MyD88 knockout (MyD88 KO) mice compared with wild
      type (WT) mice. METHODOLOGY: Periapical lesions were induced in the mandibular
      first molars of 30 WT and 30 MyD88 KO mice. After 7, 21 and 42 days, the animals
      were euthanized and the mandibles were subjected to histotechnical processing.
      Histological sections were stained with haematoxylin and eosin (HE), TRAP
      histoenzymology, Brown and Brenn staining and immunohistochemistry (RANK, RANKL,
      OPG). Data were subjected to statistical analysis by the nonparametric Mann
      Whitney and Kruskal-Wallis tests and the Dunn post-test, using the SPSS software,
      version 17.0 (alpha = 0.05). RESULTS: Regarding the periapical lesion size, the
      MyD88 KO group had significantly higher values than the WT group in the periods
      of 7 (P = 0.001) and 21 days (P = 0.05). A larger number of neutrophils in the
      MyD88 KO group were observed (P = 0.01 at 7 days, P = 0.004 at 21 days and P <
      0.001 at 42 days). Regarding the number of osteoclasts, no statistically
      significant difference was observed between the groups at any of the experimental
      periods (P = 0.884 at 7 days, P = 0.506 at 21 days and P = 0.211 at 42 days).
      CONCLUSIONS: In the absence of MyD88, the animals had larger periapical lesions,
      with a severe inflammatory infiltrate and a significantly larger number of
      neutrophils.

PMID- 24127867
TI  - Making up intelligence scales: De Sanctis's and Binet's tests, 1905 and after.
AB  - Sante De Sanctis (1862-1935) and Alfred Binet (1857-1911), the latter in
      collaboration with Theodore Simon (1873-1960), introduced their intelligence
      tests to the scientific community at the Fifth International Congress of
      Psychology, held in Rome in 1905 on April 26-30. The cultural and political
      contexts within which De Sanctis and Binet developed their respective
      intelligence tests showed certain similarities. Nevertheless, De Sanctis's
      intelligence test and Binet's test did differ in certain respects. The objective
      of this article is to understand the differences and similarities between the
      Parisian and the Roman contexts in relation to mental testing, and to investigate
      the theoretical-methodological contributions of each. In addition, the article
      analyzes the "diversity" of De Sanctis's context and test, which did not
      influence the international psychology. (PsycINFO Database Record (c) 2014 APA,
      all rights reserved). 

PMID- 24127868
TI  - Agency-communion and interest in prosocial behavior: social motives for
      assimilation and contrast explain sociocultural inconsistencies.
AB  - Identifying the "prosocial personality" is a classic project in personality
      psychology. However, personality traits have been elusive predictors of prosocial
      behavior, with personality-prosociality relations varying widely across
      sociocultural contexts. We propose the social motives perspective to account for
      such sociocultural inconsistencies. According to this perspective, a focal
      quality of agency (e.g., competence, independence, openness) is the motive to
      swim against the social tide-agentic social contrast. Conversely, a focal quality
      of communion (e.g., warmth, interdependence, agreeableness) is the motive to swim
      with the social tide-communal social assimilation. We report two cross-sectional
      studies. Study 1 (N = 131,562) defined social context at the country level (11
      European countries), whereas Study 2 (N = 56,395) defined it at the country level
      (11 European countries) and the city level (296 cities within these countries).
      Communion predicted interest in prosocial behavior comparatively strongly in
      sociocultural contexts where such interest was common and comparatively weakly
      where such interest was uncommon. Agency predicted interest in prosocial behavior
      comparatively strongly in sociocultural contexts where such interest was uncommon
      and comparatively weakly where such interest was common. The results supported
      the social motives perspective. Also, the findings help to reestablish the
      importance of personality for understanding prosociality. 

PMID- 24127869
TI  - Misdescription of packaged foods: a case study from the United Arab Emirates.
AB  - Food misdescription has become of paramount importance as consumers come into
      contact daily with a great variety of foods. The controversies surrounding
      genetically modified organism (GMO) labelling and malpractices in the food chain
      have forced regulatory authorities to authenticate food from production to
      consumption. This paper reports the results of a surveillance programme conducted
      in the United Arab Emirates (UAE) market to assess the status of food
      misdescription and authenticity. A DNA test was used to screen random samples of
      processed meat products bought from supermarkets in the UAE. A total of 246
      samples were analysed from different geographical locations. The majority of
      samples showed a high standard of legal compliance, with over 95% confirmed for
      authenticity. However, 5% of samples were found to contain undeclared species. In
      conclusion, this study confirms the presence of undeclared food in the UAE
      market. Regular surveillance and monitoring programmes along with strict
      implementation of the Food and Adulteration Act may alleviate misdescription
      issues to a greater extent. 

PMID- 24127870
TI  - Four mild but refractory cases of pemphigus foliaceus successfully treated with
      intravenous immunoglobulin.
AB  - Intravenous immunoglobulin (IVIG) is a potential second line of therapy for
      pemphigus, with increasing evidence of its effectiveness and safety, although
      oral corticosteroids remain the first treatment for pemphigus. IVIG is usually
      applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV).
      Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein
      1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant
      to corticosteroids and require long-term treatment to control the disease,
      leading to various adverse effects. IVIG was used in patients with relatively
      mild PF, who were resistant to therapies with corticosteroids and dapsone. We
      assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured
      anti-Dsg1 antibody indices by enzyme-linked immunosorbent assay, before and 4
      months after IVIG. Four Japanese female PF patients (57.3 +/- 8.6 years) were
      treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days)
      in combination with the previous therapies. Within 1-2 months of addition of
      IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also
      markedly decreased. For 2 years after IVIG, no apparent exacerbation was
      observed. Anti-Dsg1 antibody indices decreased in all cases during the 2 years.
      IVIG could be a potential treatment for not only severe cases of PV but also mild
      and refractory cases of PF. IVIG may trigger the shift from intractable condition
      to remission via non-pathogenic anti-Dsg1 antibodies or some mechanisms excluding
      anti-Dsg1 antibody.

PMID- 24127872
TI  - Feedlots and pollution-a growing threat to water resources of agro-production
      zone in Argentina.

PMID- 24127871
TI  - An update on the use of laser technology in skin vaccination.
AB  - Vaccination via skin often induces stronger immune responses than via muscle.
      This, in line with potential needle-free, painless delivery, makes skin a very
      attractive site for immunization. Yet, despite decades of effort, effective skin
      delivery is still in its infant stage and safe and potent adjuvants for skin
      vaccination remain largely undefined. We have shown that laser technologies
      including both fractional and non-fractional lasers can greatly augment vaccine
      induced immune response without incurring any significant local and systemic side
      effects. Laser illumination at specific settings can accelerate the motility of
      antigen-presenting cells or trigger release of 'danger' signals stimulating the
      immune system. Moreover, several other groups including the authors explore laser
      technologies for needle-free transcutaneous vaccine delivery. As these laser
      mediated resurfacing technologies are convenient, safe and cost-effective, their
      new applications in vaccination warrant clinical studies in the very near future.

PMID- 24127873
TI  - Targeting botulinum A cellular toxicity: a prodrug approach.
AB  - The botulinum neurotoxin light chain (LC) protease has become an important
      therapeutic target for postexposure treatment of botulism. Hydroxamic acid based
      small molecules have proven to be potent inhibitors of LC/A with nanomolar Ki
      values, yet they lack cellular activity conceivably due to low membrane
      permeability. To overcome this potential liability, we investigated two prodrug
      strategies, 1,4,2-dioxazole and carbamate, based on our 1
      adamantylacetohydroxamic acid scaffold. The 1,4,2-dioxazole prodrug did not
      demonstrate cellular activity, however, carbamates exhibited cellular potency
      with the most active compound displaying an EC50 value of 20 MUM. Cellular
      trafficking studies were conducted using a "fluorescently silent" prodrug that
      remained in this state until cellular uptake was complete, which allowed for
      visualization of the drug's release inside neuronal cells. In sum, this research
      sets the stage for future studies leveraging the specific targeting and delivery
      of these prodrugs, as well as other antibotulinum agents, into neuronal cells.

PMID- 24127874
TI  - The portfolio method as management support for patients with major depression.
AB  - AIMS AND OBJECTIVES: To describe how patients with major depression in
      psychiatric outpatient care use the portfolio method and whether the method helps
      the patients to understand their depression. BACKGROUND: Major depressive
      disorder is an increasing problem in society. Learning about one's depression has
      been demonstrated to be important for recovery. If the goal is better
      understanding and management of depression, learning must proceed on the
      patient's own terms, based on the patient's previous understanding of their
      depression. Learning must be aligned with patient needs if it is to result in
      meaningful and useful understanding. DESIGN: Each patient's portfolio consisted
      of a binder. Inside the binder, there was a register with predetermined flaps and
      questions. The patients were asked to work with the questions in the sections
      that built the content in the portfolio. METHODS: Individual interviews with
      patients (n = 5) suffering from major depression according to Diagnostic and
      Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) (American
      Psychiatric Association 1994) were repeatedly conducted between April 2008 and
      August 2009 in two psychiatric outpatient clinics in western Sweden. Data were
      analysed using latent content analysis. RESULTS: The results showed that the
      portfolio was used by patients as a management strategy for processing and
      analysis of their situation and that a portfolio's structure affects its
      usability. The patients use the portfolio for reflection on and confirmation of
      their progress, to create structure in their situation, as a management strategy
      for remembering situations and providing reminders of upcoming activities.
      CONCLUSIONS: Using a clearly structured care portfolio can enable participation
      and patient learning and help patients understand their depression. RELEVANCE TO
      CLINICAL PRACTICE: The portfolio method could provide a tool in psychiatric
      nursing that may facilitate patient understanding and increase self-efficacy.

PMID- 24127876
TI  - Tunable Rashba effect in two-dimensional LaOBiS2 films: ultrathin candidates for
      spin field effect transistors.
AB  - Rashba spin splitting is a two-dimensional (2D) relativistic effect closely
      related to spintronics. However, so far there is no pristine 2D material to
      exhibit enough Rashba splitting for the fabrication of ultrathin spintronic
      devices, such as spin field effect transistors (SFET). On the basis of first
      principles calculations, we predict that the stable 2D LaOBiS2 with only 1 nm of
      thickness can produce remarkable Rashba spin splitting with a magnitude of 100
      meV. Because the medium La2O2 layer produces a strong polar field and acts as a
      blocking barrier, two counter-helical Rashba spin polarizations are localized at
      different BiS2 layers. The Rashba parameter can be effectively tuned by the
      intrinsic strain, while the bandgap and the helical direction of spin states
      sensitively depends on the external electric field. We propose an advanced Datta
      Das SFET model that consists of dual gates and 2D LaOBiS2 channels by selecting
      different Rashba states to achieve the on-off switch via electric fields. 

PMID- 24127875
TI  - Impact of maternal negative affectivity on light alcohol use and binge drinking
      during pregnancy.
AB  - OBJECTIVES: To investigate whether maternal negative affectivity, a tendency to
      frequent negative emotions and views, is associated with light alcohol use and
      binge drinking during pregnancy. DESIGN: Cohort. SETTING: Norway 1999-2008.
      POPULATION: The study includes complete information on 66 111 pregnant women and
      their partners. METHODS: We used data from the Norwegian Mother and Child Cohort
      study (MoBa) representing 39% of the pregnant population. MAIN OUTCOME MEASURES:
      Light alcohol use (0.5-2 units one to four times per month) and binge drinking
      (an intake of 5 alcohol units or more) measured with the Alcohol Use Disorder
      Identification Test-Consumption (AUDIT-C). RESULTS: For each unit increase in
      maternal negative affectivity the odds for light alcohol use increased with 27%
      in the first trimester [95% confidence interval (CI) 1.19-1.36], and 28% in the
      second trimester (95% CI 1.18-1.39). With respect to binge drinking, each unit
      increase in maternal negative affectivity was associated with 55% higher odds in
      the first trimester (95% CI 1.44-1.67), and 114% higher odds in the second
      trimester (95% CI 1.70-2.69). CONCLUSIONS: Negative affectivity is associated
      with both light alcohol use and binge drinking during pregnancy. The mechanisms
      mediating the relation between negative affectivity and alcohol use in pregnancy
      should be investigated further.

PMID- 24127877
TI  - Development of a pretreatment system for the analysis of atmospheric reduced
      sulfur compounds.
AB  - A new pretreatment system was used to evaluate a technology to analyze reduced
      sulfur compounds (RSCs). To conduct this research, a self-developed custom dryer
      (Desolvator) and a thermal desorber system (TDS) were installed in the front of
      GC/PFPD. The syringe pump inside the TDS was devised in such a way that it can be
      desorbed in a relatively low desorption temperature and low vacuum (730 Pa). When
      comparing water removal efficiency of the Desolvator and frequently used Nafion
      dryer, the removal efficiency of the Desolvator stood between 94.6 and 96.1%,
      considerably higher and more stable than the Nafion dryer (81.3-94.5%). Moreover,
      analyses were made under various conditions in order to minimize the loss of
      samples when analyzing sulfur compounds using the TDS, and it was determined that
      adsorption temperatures less than -25  degrees C and a flow rate of 50 mL/min
      were appropriate for the efficient analysis of these sulfur compounds. Moreover,
      the desorption flow rate and the degree of a vacuum were found to be significant
      variables for the RSCs desorption. Besides, it was observed that a peculiar peak
      was formed by thermal decomposition when some sulfur compounds were rapidly
      desorbed at high desorption temperatures. 

PMID- 24127878
TI  - Costimulatory pathways in kidney transplantation: pathogenetic role, clinical
      significance and new therapeutic opportunities.
AB  - Costimulatory pathways play a key role in immunity, providing the second signal
      required for a full activation of adaptive immune response. Different
      costimulatory families (CD28, TNF-related, adhesion and TIM molecules),
      characterized by structural and functional analogies, have been described.
      Costimulatory molecules modulate T cell activation, B cell function, Ig
      production, cytokine release and many other processes, including atherosclerosis.
      Patients suffering from renal diseases present significant alterations of the
      costimulatory pathways, which might make them particularly liable to infections.
      These alterations are further pronounced in patients undergoing kidney
      transplantation. In these patients, different costimulatory patterns have been
      related to distinct clinical features. The importance that costimulation has
      gained during the last years has led to development of several pharmacological
      approaches to modulate this critical step in the immune activation. Different
      drugs, mainly monoclonal antibodies targeting various costimulatory molecules
      (i.e. anti-CD80, CTLA-4 fusion proteins, anti-CD154, anti-CD40, etc.) were
      designed and tested in both experimental and clinical studies. The results of
      these studies highlighted some criticisms, but also some promising findings and
      now costimulatory blockade is considered a suitable strategy, with belatacept (a
      CTLA-4 fusion protein) being approved as the first costimulatory blocker for use
      in renal transplantation. In this review, we summarize the current knowledge on
      costimulatory pathways in the setting of kidney transplantation. We describe the
      principal costimulatory molecule families, their role and clinical significance
      in patients undergoing renal transplantation and the new therapeutic approaches
      that have been developed to modulate the costimulatory pathways. 

PMID- 24127879
TI  - Incidence and prediction of outcome in hypoxic-ischemic encephalopathy in Japan.
AB  - BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the most critical
      pathologic conditions in neonatal medicine due to the potential for neurological
      deficits in later life. We investigated the incidence of term infants with
      moderate or severe HIE in Japan and identified prognostic risk factors for poor
      outcome in HIE. METHODS: Data on 227 infants diagnosed with moderate or severe
      HIE and born between January and December 2008 were collected via nationwide
      surveys from 263 responding hospitals. Using logistic regression, we examined the
      relationship between maternal, antepartum, intrapartum, and neonatal risk factors
      and clinical outcome at 18 months following birth. RESULTS: In Japan, the
      incidence of moderate or severe HIE was 0.37 per 1000 term live births. Outborn
      births, low Apgar score at 5 min, use of epinephrine, and low cord blood pH were
      intrapartum factors significantly associated with neurodevelopmental delay and
      death at 18 months. Serum lactate, lactate dehydrogenase, aspartate
      aminotransferase, alanine aminotransferase (all, P < 0.001) and creatine kinase
      (P = 0.002) were significantly higher in infants with poor outcome compared to
      those with favorable outcomes. Abnormal brain magnetic resonance imaging (MRI),
      an important prognostic factor, was significantly associated with poor outcome
      (odds ratio, 11.57; 95% confidence interval: 5.66-23.64; P < 0.001). CONCLUSIONS:
      Risk factors predicting poor outcome in HIE include outborn birth, low Apgar
      score at 5 min, use of epinephrine, laboratory abnormalities, and abnormal MRI
      findings.

PMID- 24127880
TI  - Endoscopic submucosal dissection for gastric cancer in elderly Japanese patients:
      an observational study of financial costs of treatment based on a national
      administrative database.
AB  - OBJECTIVE: There is currently little information on the medical economic outcomes
      of endoscopic submucosal dissection (ESD) for gastric cancer (GC) in elderly
      patients. This study therefore aimed to investigate the medical economic outcomes
      of ESD in elderly patients with GC using a national administrative database.
      METHODS: A total of 27 385 patients treated with ESD for GC were referred to 867
      hospitals in Japan from 2009 to 2011. We collected data from the national
      administrative database and divided them into two groups according to age:
      elderly patients (>=80 years; n = 5525) and non-elderly patients (<80 years; n =
      21 860). We compared ESD-related complications, risk-adjusted length of stay
      (LOS) and medical costs during hospitalization between elderly and non-elderly
      patients. RESULTS: There was no significant difference in ESD-related
      complications between elderly and non-elderly patients (4.3% vs 3.9%, P = 0.152).
      However, significant differences were observed in mean LOS and medical costs
      during hospitalization between the two groups (P < 0.001). Multiple linear
      regression analysis showed that elderly patients experienced a significantly
      longer LOS and higher medical costs. The unstandardized coefficient for LOS in
      elderly patients was 2.71 days (95% confidence interval [CI] 2.59-2.84, P <
      0.001), while that for medical costs during hospitalization was USD952.1 (95% CI
      847.7-1056.5, P < 0.001). CONCLUSIONS: LOS and medical costs during
      hospitalization were significantly higher in elderly patients undergoing ESD for
      GC than in non-elderly patients, although there was no difference in the
      incidence of ESD-related complications.

PMID- 24127881
TI  - Postnatal nutrition in extremely low birth weight infants and its impact on
      growth until the age of 6 years.
AB  - AIM: To examine the impact of postnatal nutrition on long-term growth in
      extremely low birth weight infants. METHOD: Retrospective analysis of postnatal
      nutrition and observational study of growth in 52 ELBW infants until the age of
      six. RESULTS: Changes (Delta) in weight and length standard deviation scores
      (SDS) between birth to term correlated with protein intake (r(w) = 0.36; p =
      0.009; r(L) = 0.35; p = 0.01), whereas DeltaHC correlated with lipid intake
      (r(HC) = 0.38; p = 0.005). Analysis of various intervals (0-2, 3-5, 6-8 and 9-11
      weeks) only showed significant impact on growth for energy (r = 0.3; p < 0.05)
      and lipids (r = 0.23; p < 0.05) at 6-8 weeks. No significant correlations were
      found between postnatal nutritional parameters and long-term growth. However,
      postnatal growth restraint was negatively associated with length SDS (r = -0.34;
      p = 0.015) and body mass index SDS (r = -0.34; p = 0.018) at the age of six.
      Infants with postnatal growth restraint (n = 25) caught up more in length (+1.78
      SDS) than in weight (+0.43 SDS), whereas small for gestational age infants (n =
      8) caught up more in weight (+1.35 SDS) than in length (+1.07 SDS). This
      difference remained significant at the age of six. CONCLUSION: Although no direct
      association between postnatal nutrition and long-term growth was found, weight at
      discharge was a strong predictor for long-term growth.

PMID- 24127882
TI  - Cyclooxygenase-2 inhibitor suppresses tumour progression of prostate cancer bone
      metastases in nude mice.
AB  - OBJECTIVE: To assess whether celecoxib, a selective cyclooxygenase-2 (COX-2)
      inhibitor with anti-cancer properties, has an inhibitory effect on tumour
      establishment and progression of prostate cancer (PCa) bone metastases. MATERIALS
      AND METHODS: PC-3 stable luciferase-expressing cells were injected into male nude
      mice by intracardiac (i.c.) and intratibial (i.t.) injections, and the effect of
      celecoxib on bone metastases was then recorded using bioluminescence image
      analysis. In cases of chemoprevention, mice received 3 mg/kg celecoxib from 1
      week before cell implantation until the end of the study, and to test the
      therapeutic effect, mice received celecoxib 1 week after cell implantation until
      the end of the study. Tumour tissue samples were histologically examined and COX
      2 expression was quantified at the protein level. RESULTS: Celecoxib
      significantly decreased cell viability and the proliferation of human PCa cells
      in vitro in a dose-dependent manner. Bone metastases were detected after i.c.
      injection in nude mice. Celecoxib (15 ppm) administered before i.c. injection did
      not inhibit the cellular metastatic potential, as the numbers of bone metastases
      were similar in both groups. However, celecoxib did decrease metastatic
      progression in the osseous environment when cells were injected directly into the
      tibia (P < 0.05). At the protein level, COX-2 expression was significantly
      decreased in the celecoxib treatment group (P < 0.01). CONCLUSION: In a
      preclinical mice model, celecoxib administered orally at the standard human dose
      inhibits the progression of established PCa bone metastases.

PMID- 24127884
TI  - Tandem Blaise/retro-Blaise reaction for the nitrile-mediated regioselective
      intermolecular addition of unstabilized zinc ester enolates (Reformatsky
      reagents) to 1-alkynes and 1,3-enynes.
AB  - We report the novel use of a nitrile as a mediator to achieve the regioselective
      intermolecular addition of unstabilized zinc ester enolates (Reformatsky
      reagents) to 1-alkynes and 1,3-enynes. This reaction is made possible by a
      reversible addition of enolates to a nitrile (Blaise reaction), generating a zinc
      aza-enolate that, unlike zinc ester enolates, can add intermolecularly to 1
      alkynes and 1,3-enynes. Subsequent removal of the nitrile through a retro-Blaise
      reaction generates the targeted addition product. This method is combined with a
      Diels-Alder reaction and subsequent oxidative aromatization, providing a tandem
      one-pot de novo construction of alpha-arylated alkanoates from Reformatsky
      reagents. 

PMID- 24127883
TI  - Economic aspects of implementing genomic evaluations in a pig sire line breeding
      scheme.
AB  - BACKGROUND: Replacing pedigree-based BLUP evaluations by genomic evaluations in
      pig breeding schemes can result in greater selection accuracy and genetic gains,
      especially for traits with limited phenotypes. However, this methodological
      change would generate additional costs. The objective of this study was to
      determine whether additional expenditures would be more profitably devoted to
      implementing genomic evaluations or to increasing phenotyping capacity while
      retaining traditional evaluations. METHODS: Stochastic simulation was used to
      simulate a population with 1050 breeding females and 50 boars that was selected
      for 10 years for a breeding goal with two uncorrelated traits with heritabilities
      of 0.4. The reference breeding scheme was based on phenotyping 13 770 candidates
      per year for trait 1 and 270 sibs of candidates per year for trait 2, with
      selection based on pedigree-based BLUP estimated breeding values. Increased
      expenditures were allocated to either increasing the phenotyping capacity for
      trait 2 while maintaining traditional evaluations, or to implementing genomic
      selection. The genomic scheme was based on two training populations: one for
      trait 2, consisting of phenotyped sibs of the candidates whose number increased
      from 1000 to 3430 over time, and one for trait 1, consisting of the selection
      candidates. Several genomic scenarios were tested, where the size of the training
      population for trait 1, and the number of genotyped candidates pre-selected based
      on their parental estimated breeding value, varied. RESULTS: Both approaches
      resulted in higher genetic trends for the population breeding goal and lower
      rates of inbreeding compared to the reference scheme. However, even a very marked
      increase in phenotyping capacity for trait 2 could not match improvements
      achieved with genomic selection when the number of genotyped candidates was
      large. Genotyping just a limited number of pre-selected candidates significantly
      reduced the extra costs, while preserving most of the benefits in terms of
      genetic trends and inbreeding. Implementing genomic evaluations was the most
      efficient approach when major expenditure was possible, whereas increasing
      phenotypes was preferable when limited resources were available. CONCLUSIONS:
      Economic decisions on implementing genomic evaluations in a pig nucleus
      population must take account of population characteristics, phenotyping and
      genotyping costs, and available funds.

PMID- 24127885
TI  - Liquid crystalline perylene diimide outperforming nonliquid crystalline
      counterpart: higher power conversion efficiencies (PCEs) in bulk heterojunction
      (BHJ) cells and higher electron mobility in space charge limited current (SCLC)
      devices.
AB  - In this work, we propose the application of liquid crystalline acceptors as a
      potential means to improve the performances of bulk heterojunction (BHJ) organic
      solar cells. LC-1, a structurally-simple perylene diimide (PDI), has been adopted
      as a model for thorough investigation. It exhibits a broad temperature range of
      liquid crystalline (LC) phase from 41  degrees C to 158  degrees C, and its LC
      properties have been characterized by differental scanning calorimetry (DSC),
      polarization optical microscopy (POM), and X-ray diffraction (XRD). The BHJ
      devices, using P3HT:LC-1 (1:2) as an organic photovoltaic active layer undergoing
      thermal annealing at 120  degrees C, shows an optimized efficiency of 0.94 %. By
      contrast, the devices based on PDI-1, a nonliquid crystalline PDI counterpart,
      only obtain a much lower efficiency of 0.22%. Atomic force microscopy (AFM)
      images confirm that the active layers composed of P3HT:LC-1 have smooth and
      ordered morphology. In space charge limited current (SCLC) devices fabricated via
      a spin-coating technique, LC-1 shows the intrinsic electron mobility of 2.85 *
      10(-4) cm(2)/(V s) (at 0.3 MV/cm) which is almost 5 times that of PDI-1 (5.83 *
      10(-5) cm(2)/(V s)) under the same conditions for thermal annealing at 120 
      degrees C. 

PMID- 24127886
TI  - Prevalence of metabolic syndrome in hypertriglyceridaemic patients: higher than
      it may appear.

PMID- 24127887
TI  - Dental pulp stem cells immobilized in alginate microspheres for applications in
      bone tissue engineering.
AB  - AIM: To immobilize dental pulp stem cells (DPSC) in alginate microspheres and to
      determine cell viability, proliferation, stem cell characteristics and osteogenic
      potential of the immobilized DPSCs. METHODOLOGY: Human DPSCs isolated from the
      dental pulp were immobilized in 1% w/v alginate microspheres. Viability and
      proliferation of immobilized DPSCs were determined by trypan blue and MTT assay,
      respectively. Stem cell characteristics of DPSCs post immobilization were
      verified by labelling the cells with CD73 and CD90. Osteogenic potential of
      immobilized DPSCs was assessed by the presence of osteocalcin. Alizarin red
      staining and O-cresolphthalein complexone method confirmed and quantified calcium
      deposition. A final reverse transcriptase PCR evaluated the expression of
      osteogenic markers - ALP, Runx-2 and OCN. RESULTS: More than 80% of immobilized
      DPSCs were viable throughout the 3-week study. Proliferation appeared controlled
      and consistent unlike DPSCs in the control group. Presence of CD73 and CD90
      markers confirmed the stem cell nature of immobilized DPSCs. The presence of
      osteocalcin, an osteoblastic marker, was confirmed in the microspheres on day 21.
      Mineralization assays showed high calcium deposition indicating elevated
      osteogenic potential of immobilized DPSCs. Osteogenic genes- ALP, Runx-2 and OCN
      were also upregulated in immobilized DPSCs. Surprisingly, immobilized DPSCs in
      the control group cultured in conventional stem cell media showed upregulation of
      osteogenic genes and expressed osteocalcin. CONCLUSION: Dental pulp stem cells
      immobilized in alginate hydrogels exhibit enhanced osteogenic potential while
      maintaining high cell viability both of which are fundamental for bone tissue
      regeneration.

PMID- 24127888
TI  - The role and reliability of the Psychopathy Checklist-Revised in U.S. sexually
      violent predator evaluations: a case law survey.
AB  - The civil commitment of offenders as sexually violent predators (SVPs) is a
      highly contentious area of U.S. mental health law. The Psychopathy Checklist
      Revised (PCL-R) is frequently used in mental health evaluations in these cases to
      aid legal decision making. Although generally perceived to be a useful assessment
      tool in applied settings, recent research has raised questions about the
      reliability of PCL-R scores in SVP cases. In this report, we review the use of
      the PCL-R in SVP trials identified as part of a larger project investigating its
      role in U.S. case law. After presenting data on how the PCL-R is used in SVP
      cases, we examine the reliability of scores reported in these cases. We located
      214 cases involving the PCL-R, 88 of which included an actual score and 29 of
      which included multiple scores. In the 29 cases with multiple scores, the
      intraclass correlation coefficient for a single evaluator for the PCL-R scores
      was only .58, and only 41.4% of the difference scores were within 1 standard
      error of measurement unit. The average score reported by prosecution experts was
      significantly higher than the average score reported by defense-retained experts,
      and prosecution experts reported PCL-R scores of 30 or above in nearly 50% of the
      cases, compared with less than 10% of the cases for defense witnesses (kappa =
      .29). In conjunction with other recently published findings demonstrating the
      unreliability of PCL-R scores in applied settings, our results raise questions as
      to whether this instrument should be admitted into SVP proceedings.

PMID- 24127889
TI  - Archival analyses of eyewitness identification test outcomes: what can they tell
      us about eyewitness memory?
AB  - Several archival studies of eyewitness identification have been conducted, but
      the results have been inconsistent and contradictory. We identify some avoidable
      pitfalls that have been present in previous analyses and present new data that
      address these pitfalls. We explored associations among various estimator
      variables and lineup outcomes for 833 "real life" lineups, including 588 lineups
      in which corroborating evidence of the suspect's guilt existed. Suspect
      identifications were associated with exposure duration, viewing distance, and the
      age of the witness. Nonidentifications were associated with the number of
      perpetrators. We also consider some of the inherent, unavoidable limitations with
      archival studies and consider what such studies can really tell researchers. We
      conclude that differences in sampling prohibit sensible comparisons between the
      results of laboratory and archival studies, and that the informational value of
      archival studies is actually rather limited.

PMID- 24127890
TI  - Gender differences in recidivism rates for juvenile justice youth: the impact of
      sexual abuse.
AB  - Young female offenders represent a growing number of young offenders. Studies
      have shown that youth in the juvenile justice system, particularly young females,
      report higher rates of lifetime sexual abuse than their nonoffending peers. The
      aim of this study was to examine gender differences in risk factors for
      recidivism, including a history of sexual abuse, among a juvenile court clinic
      sample. Findings suggest that, even after accounting for previously identified
      risk factors for recidivism such as prior legal involvement and conduct problems,
      a history of sexual abuse is the most salient predictor of recidivism for young
      female offenders, but not for males. The development of gender-responsive
      interventions to reduce juvenile recidivism and continued legal involvement into
      adulthood may be warranted.

PMID- 24127891
TI  - Interrogations, confessions, and guilty pleas among serious adolescent offenders.
AB  - In the present study, we examined (a) the prevalence and characteristics of
      youths' true and false admissions (confessions and guilty pleas), (b) youths'
      interrogation experiences with police and lawyers, and (c) whether youths'
      interrogation experiences serve as situational risk factors for true and false
      admissions. We interviewed 193 14- to 17-year-old males (M = 16.4) incarcerated
      for serious crimes. Over 1/3 of the sample (35.2%) claimed to have made a false
      admission to legal authorities (17.1% false confession; 18.1% false guilty plea),
      and 2/3 claimed to have made a true admission (28.5% true confession; 37.3% true
      guilty plea). The majority of youth said that they had experienced high-pressure
      interrogations (e.g., threats), especially with police officers. Youth who
      mentioned experiencing "police refusals" (e.g., of a break to rest) were more
      likely to report having made both true and false confessions to police, whereas
      only false confessions were associated with claims of long interrogations (>2 hr)
      and being questioned in the presence of a friend. The number of self-reported
      high-pressure lawyer tactics was associated with false, but not true, guilty
      pleas. Results suggest the importance of conducting specialized trainings for
      those who interrogate youth, recording interrogations, placing limits on lengthy
      and manipulative techniques, and exploring alternative procedures for questioning
      juvenile suspects.

PMID- 24127892
TI  - Crime and substance misuse in adjudicated delinquent youth: the worst of both
      worlds.
AB  - The purpose of this study was to determine whether comorbid offending and
      substance misuse in previously adjudicated delinquents correlated better with
      measures of concurrent antisocial cognition and personality and subsequent
      criminality and substance misuse than offending or substance misuse alone. A
      sample of 1,177 youths was divided into four groups based on self-reported crime
      and substance misuse data from Wave 4 (ages 16-21) of the Pathways to Desistance
      study (Mulvey, 2012): a no-crime and substance-misuse (NCS) group, a crime-only
      (CO) group, a substance-misuse-only (SO) group, and a crime and substance-misuse
      (C&S) group. As predicted, youths in the C&S group earned significantly higher
      scores on concurrent measures of neuroticism, grandiosity/manipulation,
      callousness/unemotionality, impulsivity/irresponsibility, and moral
      disengagement, and significantly lower scores on measures of agreeableness,
      conscientiousness, impulse control, suppression of aggression, and consideration
      of others than did youths in the other three groups. Prospective analyses
      revealed that C&S participants engaged in more subsequent crime and experienced
      more substance-related social problems than participants in the other three
      groups and reported significantly more substance-related dependency symptoms and
      episodes of alcohol/drug treatment than participants in the NCS and CO groups.
      Hence, previously adjudicated youths who experienced problems with crime and
      substances in late adolescence/early adulthood were at increased risk for
      concurrent antisocial cognition and personality problems and subsequent crime and
      substance-misuse problems compared with participants in the other three groups.
      The prospective effects were found to be partially mediated by antisocial
      cognition in the form of moral disengagement.

PMID- 24127893
TI  - Procedural justice versus risk factors for offending: predicting recidivism in
      youth.
AB  - Theories of procedural justice suggest that individuals who experience respectful
      and fair legal decision-making procedures are more likely to believe in the
      legitimacy of the law and, in turn, are less likely to reoffend. However, few
      studies have examined these relationships in youth. To begin to fill this gap in
      the literature, in the current study, the authors studied 92 youth (67 male, 25
      female) on probation regarding their perceptions of procedural justice and
      legitimacy, and then monitored their offending over the subsequent 6 months.
      Results indicated that perceptions of procedural justice predicted self-reported
      offending at 3 months but not at 6 months, and that youths' beliefs about the
      legitimacy of the law did not mediate this relationship. Furthermore, procedural
      justice continued to account for unique variance in self-reported offending over
      and above the predictive power of well-established risk factors for offending
      (i.e., peer delinquency, substance abuse, psychopathy, and age at first contact
      with the law). Theoretically, the current study provides evidence that models of
      procedural justice developed for adults are only partially replicated in a sample
      of youth; practically, this research suggests that by treating adolescents in a
      fair and just manner, justice professionals may be able to reduce the likelihood
      that adolescents will reoffend, at least in the short term.

PMID- 24127894
TI  - Major mental illness and violence history as predictors of institutional
      misconduct and recidivism: main and interaction effects.
AB  - The purpose of this study was to ascertain whether major mental illness (MMI) and
      violence history (VH) interact in their effect on institutional misconduct and
      recidivism. MMI and VH were measured in two overlapping groups of male medium
      security federal prisoners and correlated with institutional misconduct and
      recidivism. Age and the main effect of MMI were significant predictors of general
      and aggressive infractions in 2,627 male prison inmates before the MMI * VH
      interaction term was entered into a Cox regression equation. Once the interaction
      term was entered into the equation, the MMI * VH interaction predicted relative
      hazard (risk) but neither main effect (MMI, VH) was significant. There was no
      interaction effect, however, when age, prior substance abuse, MMI, VH, and the
      MMI * VH interaction were used to predict general and aggressive recidivism in a
      group of 1,163 male inmates previously released from custody. Age and the VH main
      effect achieved significance in both recidivism analyses whereas the MMI main
      effect failed to achieve significance in either analysis. Whereas major mental
      illness was not a risk factor for future antisocial behavior in current and
      former prison inmates, when paired with a history of violence it predicted
      increased risk of general and aggressive institutional misconduct. Violence
      history, on the other hand, was a consistent predictor of recidivism. These
      results indicate that it may be advisable to review both mental health and
      violence history when screening inmates as a prelude to managing concomitant MMI
      and violence propensity.

PMID- 24127895
TI  - Young children's understanding that promising guarantees performance: the effects
      of age and maltreatment.
AB  - Two studies, with 102 nonmaltreated 3- to 6-year-old children and 96 maltreated 4
      to 7-year-old children, examined children's understanding of the relative
      strengths of "I promise," "I will," "I might," and "I won't," to determine the
      most age-appropriate means of eliciting a promise to tell the truth from child
      witnesses. Children played a game in which they chose which of 2 boxes would
      contain a toy after hearing story characters make conflicting statements about
      their intent to place a toy in each box (e.g., one character said "I will put a
      toy in my box" and the other character said "I might put a toy in my box").
      Children understood "will" at a younger age than "promise." Nonmaltreated
      children understood that "will" is stronger than "might" by 3 years of age and
      that "promise" is stronger than "might" by 4 years of age. The youngest
      nonmaltreated children preferred "will" to "promise," whereas the oldest
      nonmaltreated children preferred "promise" to "will." Maltreated children
      exhibited a similar pattern of performance, but with delayed understanding that
      could be attributed to delays in vocabulary. The results support a modified oath
      for children: "Do you promise that you will tell the truth?".

PMID- 24127896
TI  - Field reliability of the Psychopathy Checklist-Revised among life sentenced
      prisoners in Sweden.
AB  - Although typically described as reliable and valid, the Psychopathy Checklist
      Revised (PCL-R) has come under some criticism by researchers in the last half
      decade due to evidence of poor interrater reliability and adversarial allegiance
      being reported in applied settings in North America. This study examines the
      field reliability of the PCL-R using a naturalistic test-retest design among a
      sample of Swedish life sentenced prisoners (N = 27) who had repeatedly been
      assessed as part of their application to receive a reduced prison term. The
      prisoners, who were assessed by a team of forensic evaluators retained by an
      independent government authority, had spent on average 14 years in prison with a
      mean time from Assessment 1 to Assessment 2 of 2.33 years. The overall
      reliability of the PCL-R (ICC(A1)) was .70 for the total score and .62 and .76
      for Factor 1 and 2 scores, respectively. Facet 1-3 scores ranged from .54 to .60,
      whereas Facet 4 was much higher (.90). Reliability of individual items was quite
      variable, ranging from .23 to .80. In terms of potential causes of unreliability,
      both high and low PCL-R scores at the initial assessment tended to regress toward
      the mean at the time of the second evaluation. Our results are in line with
      previous research demonstrating concerns regarding the reliability of the PCL-R
      within judicial settings, even among independent evaluation teams not retained by
      a particular side in a case. Collectively, these findings question whether the
      interpersonal (Facet 1) and affective (Facet 2) features tapped by the PCL-R are
      reliable enough to justify their use in legal proceedings.

PMID- 24127897
TI  - Predicting involvement in prison gang activity: street gang membership, social
      and psychological factors.
AB  - The aim of this study was to examine whether street gang membership,
      psychological factors, and social factors such as preprison experiences could
      predict young offenders' involvement in prison gang activity. Data were collected
      via individual interviews with 188 young offenders held in a Young Offenders
      Institution in the United Kingdom. Results showed that psychological factors such
      as the value individuals attached to social status, a social dominance
      orientation, and antiauthority attitudes were important in predicting young
      offenders' involvement in prison gang activity. Further important predictors
      included preimprisonment events such as levels of threat, levels of individual
      delinquency, and levels of involvement in group crime. Longer current sentences
      also predicted involvement in prison gang activity. However, street gang
      membership was not an important predictor of involvement in prison gang activity.
      These findings have implications for identifying prisoners involved in prison
      gang activity and for considering the role of psychological factors and group
      processes in gang research.

PMID- 24127898
TI  - Effect of blockade of the EGF system on wound healing in patients vaccinated with
      CIMAvax(r) EGF.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) signaling system is
      frequently unbalanced in human malignancies due to increased ligand production,
      receptor overexpression, receptor mutations, and/or cross-talk with other
      receptor systems. For this reason, the EGFR is an attractive target for
      anticancer therapy. The epidermal growth factor also plays an important role in
      regulating multiple facets of cutaneous wound healing, including inflammation,
      wound contraction, proliferation, migration, and angiogenesis. In the Center of
      Molecular Immunology, a cancer vaccine is produced (CIMAvax(r) EGF) that blocks
      the binding of EGF to its receptor. This blockade causes a significant inverse
      association between the anti-EGF antibody titers and EGF concentration. Around
      1,500 patients with non-small cell lung cancer have been treated, showing that
      this vaccine is safe, immunogenic, increases survival and improves quality of
      life. Taking into account the therapeutic benefits of CIMAvax(r) EGF vaccination
      and the role of EGF-EGFR system in the wound healing process, we decided to
      conduct a retrospective research with the aim of determining the effect to the
      CIMAvax(r) EGF vaccine on the wound healing process in patients undergoing
      surgical treatment. METHODS: Medical records of 452 vaccinated patients were
      reviewed and only six patients receiving surgical treatment were identified.
      Further information about these six patients was obtained from source documents,
      including medical records and operative reports using an observational list that
      included different variables. Post-surgical wound healing complications were
      identified using the National Cancer Institute Common Toxicity Criteria for
      Adverse Events (NCI-CTC) version 3.0. RESULTS: None of the six patients operated
      on presented adverse events related to the wound healing, that is to say, no
      wound dehiscence, wound infection, delayed wound healing, fistula formation,
      abscess formation or hemorrhage/bleeding associated with surgery during treatment
      with CIMAvax(r) EGF occurred. CONCLUSIONS: These results suggest that the use of
      CIMAvax(r) EGF does not produce a deleterious effect in the wound healing
      process.

PMID- 24127899
TI  - The EAL-like protein STM1697 regulates virulence phenotypes, motility and biofilm
      formation in Salmonella typhimurium.
AB  - The ubiquitous second messenger c-di-GMP regulates the switching of bacterial
      lifestyles from motility to sessility and acute to chronic virulence to adjust
      bacterial fitness to altered environmental conditions. Conventionally, EAL
      proteins being c-di-GMP phosphodiesterases promote motility and acute virulence
      phenotypes such as invasion into epithelial cells and inhibit biofilm formation.
      We report here that in contradiction, the EAL-like protein STM1697 of Salmonella
      typhimurium suppresses motility, invasion into HT-29 epithelial cell line and
      secretion of the type three secretion system 1 effector protein SipA, whereas it
      promotes rdar biofilm formation and CsgD expression. STM1697 can, however,
      functionally replace the EAL-like protein STM1344 and vice versa, whereby both
      proteins neither degrade nor bind c-di-GMP. Like STM1344, STM1697 suppresses the
      transcription of class 2 and class 3 flagella regulon genes by binding to FlhD, a
      component of the master regulator of the flagella regulon FlhD4 C2 and act
      additively under numerous conditions. Interestingly, the interaction interface of
      STM1697 with FlhD2 is distinct from its paralogue STM1344. We predict that the
      stand alone EAL domain proteins STM1697 and STM1344 belong to a subclass of EAL
      domain proteins in S. typhimurium, which are all involved in motility, biofilm
      and virulence regulation through interaction with proteins that regulate flagella
      function. 

PMID- 24127900
TI  - Skin tag of the nipple with blister formation: two case reports.

PMID- 24127901
TI  - Support utilization by partners of self-identified sex addicts.
AB  - This online survey examined the support resources used by partners of sex
      addicts. Partners (N = 92) answered questions about which sources of support they
      found most useful, relationship functioning, and demographic and background
      variables. Partners rated therapists, spirituality, support groups, and friends
      as most useful; and the mate, their children, and their other family members as
      least useful. Participants indicated that they used intrapersonal
      religious/spiritual activities (e.g., prayer and meditation) more than
      interpersonal religious/spiritual activities (e.g., religious services and
      support groups). Older partners sought more religious/spiritual support, and more
      educated partners rated therapy as more useful. Rating the mate as useful was
      most strongly associated with positive relationship outcomes. The authors
      conclude with recommendations for working with partners of sex addicts. 

PMID- 24127902
TI  - Open and robot-assisted radical retropubic prostatectomy in men receiving ongoing
      low-dose aspirin medication: revisiting an old paradigm?
AB  - OBJECTIVE: To assess blood loss, transfusion rates and 90-day complication rates
      in patients receiving ongoing 100 mg/day aspirin medication and undergoing open
      radical prostatectomy (RP) or robot-assisted RP (RARP). PATIENTS AND METHODS:
      Between February 2010 and August 2011, 2061 open RPs and 400 RARPs were
      performed. All patients received low-molecular-weight heparin for thrombembolism
      prophylaxis. Aspirin intake during surgery was recorded in 137 patients (5.5%).
      Descriptive statistics and multivariable analyses after propensity-score matching
      for balancing potential differences in patients with and without aspirin
      medication were used to assess the risk of blood loss above the median in
      patients undergoing open RP or RARP. RESULTS: The median blood loss in the open
      RP cohort with and without aspirin medication was 750 and 700 mL, respectively,
      and in the RARP cohort it was 200 and 150 mL, respectively. Within the same
      cohorts, transfusions were administered in 21 and 8% and 0 and 1% of patients,
      respectively. The 90-day complication rates in patients with ongoing aspirin
      medication were 5.8, 4.4, 7.3 and 0% for Clavien grades I, II, III and IV
      complications, respectively. In multivariable analyses and after propensity-score
      matching, prostate volume (odds ratio 1.03; 95% CI 1.02-1.04; P < 0.01) but not
      ongoing aspirin medication achieved independent predictor status for the risk of
      blood loss above the median. CONCLUSIONS: Major surgery such as open RP and RARP
      can be safely performed in patients with ongoing aspirin medication without
      greater blood loss. Higher 90-day complication rates were not detected in such
      patients. Differences in transfusion rates between the groups receiving and not
      receiving ongoing aspirin medication may be explained by a higher proportion of
      patients with coronary artery disease in the group receiving ongoing aspirin
      medication. This comorbidity may result in a higher peri-operative threshold for
      allogenic blood transfusion.

PMID- 24127903
TI  - Have we neglected the role of fetal endothelium in transplacental transport?
AB  - Maternal-to-fetal transfer of nutrient and other substances occurs across the
      placental barrier (PB) which is made up of endothelial cells (EC) on the fetal
      side and the syncytiotrophoblast (STB) on the maternal side. Numerous studies
      were conducted to explore the transport characteristics across the STB layer,
      which is also considered as the major resistance for maternal-to-fetal exchange
      of materials. In contrast the layer of EC has received very little attention if
      at all. A recently developed viable co-culture model of the PB revealed
      significant resistance of the EC layer for maternal-to-fetal transfer of glucose.
      This argues for a major contribution of the EC to overall transplacental transfer
      of nutrients. Accordingly, it is recommended to fill the void of knowledge and
      expand our understanding on the role of the feto-placental endothelium for
      transplacental transport characteristics. 

PMID- 24127904
TI  - Microneedle-mediated intrascleral delivery of in situ forming thermoresponsive
      implants for sustained ocular drug delivery.
AB  - OBJECTIVES: This paper describes use of minimally invasive hollow microneedle
      (HMN) to deliver in situ forming thermoresponsive poloxamer-based implants into
      the scleral tissue to provide sustained drug delivery. METHODS: In situ forming
      poloxamer formulations were prepared and investigated for their rheological
      properties. HMN devices 400, 500 and 600 MUm in height were fabricated from
      hypodermic needles (i.e. 27, 29 and 30 G) and tested for depth of penetration
      into rabbit sclera. Maximum force and work required to expel different volumes of
      poloxamer formulations was also investigated. Release of fluorescein sodium (FS)
      from intrasclerally injected implants was also investigated. Optical coherence
      tomography (OCT) was used to examine implant localisation and scleral pore
      closure. KEY FINDINGS: Poloxamer formulations showed Newtonian behaviour at 20
      degrees C and pseudoplastic (shear-thinning) behaviour at 37 degrees C. Maximum
      force and work required to expel different volumes of poloxamer formulations with
      different needles ranged from 0.158 to 2.021 N and 0.173 to 6.000 N,
      respectively. OCT showed intrascleral localisation of implants and scleral pore
      closure occurred within 2-3 h. Sustain release of FS was noticed over 24 h and
      varied with depth of implant delivery. CONCLUSIONS: This study shows that the
      minimally invasive HMN device can localise in situ forming implants in the
      scleral tissue and provide sustained drug delivery.

PMID- 24127905
TI  - Repeatability and reliability of human eye in visual shade selection.
AB  - Deficiencies in the human visual percep-tion system have challenged the
      efficiency of the visual shade-matching protocol. The aim of this study was to
      evaluate the repeatability and reliability of human eye in visual shade
      selection. Fifty-four volunteering dentists were asked to match the shade of an
      upper right central incisor tooth of a single subject. The Vita 3D-Master shade
      guide was used for the protocol. Before each shade-matching procedure, the
      definitive codes of the shade tabs were hidden by an opaque strip and the shade
      tabs were placed into the guide randomly. The procedure was repeated 1 month
      later to ensure that visual memory did not affect the results. The L*, a* and b*
      values of the shade tabs were measured with a dental spectrophotometer (Vita
      Easyshade) to produce quantitative values to evaluate the protocol. The paired
      samples t-test and Pearson correlation test were used to compare the 1st and 2nd
      selections. The Yates-corrected chi-square test was use to compare qualitative
      values. Statistical significance was accepted at P < 0.05. Comparing baseline and
      1st month records, statistical significance (P < 0.001) was found among
      qualitative data regarding repeatability on a yes/no (1/0) basis, revealing a
      very low percentage of repeatability (11.1%). Comparing baseline and 1st month
      records, statistical significance was not found (P = 0.000) among the L*, a*, b*
      and DeltaE variables. These results indicate that dentists perform insufficiently
      regarding repeatability in visual shade matching, but they are able to select
      clinically acceptable shades. 

PMID- 24127906
TI  - The Self-assessment for Organizational Capacity Instrument for evidence-informed
      health policy: preliminary reliability and validity of an instrument.
AB  - BACKGROUND: Health policymakers work in organizations that involve multiple
      competing demands and limited time to make decisions. Influential international
      policy organizations continue to publish guidance and recommendations without the
      use of high-quality research evidence. Few studies have described the process
      with which governments, including health ministries, use evidence to support
      health policymaking decisions. Research is needed to better understand the
      psychometric properties of instruments that assess health policy organizations'
      capacity to use research evidence. AIM: The purpose of this study was to assess
      the preliminary psychometric properties of an instrument which assesses
      organizational capacity for evidence use. METHODS: The instrument was
      administered by telephone survey from January to June 2011 using a purposeful
      sample of 57 Canadian health policymakers (policy analyst and senior management
      levels). Reliability of the instrument was assessed with Cronbach's alpha
      coefficient and item-to-total correlation for internal consistency; interitem
      coefficients were used to identify particular item redundancy. Discriminant
      validity was assessed using the known-group comparison approach, with the
      independent sample t-test to assess subscale responses of policy analysts and
      senior managers. FINDINGS: Cronbach's alpha indicated acceptable internal
      consistency across its subscales. Discriminant validity analysis revealed a
      statistically significant difference between policy analysts and senior managers
      for one subscale. LINKING EVIDENCE TO ACTION: Our study provides a first look at
      the Self-assessment for Organizational Capacity Instrument's psychometric
      properties and demonstrates that this instrument can be useful when evaluating
      government and other organizations' use of evidence to inform decision making.
      Further testing of this instrument is needed using large and varied samples of
      policymakers, from policy analysts to senior managers, across varied policymaking
      contexts. This instrument can be a starting point for government and related
      organizations to better understand how well it supports evidence use, including
      its acquisition, appraisal, and use in health policy decision making.

PMID- 24127908
TI  - Turkish nursing students' knowledge of and attitudes towards patients with
      HIV/AIDS.
AB  - AIMS AND OBJECTIVES: To assess nursing students' knowledge of and attitudes
      towards such patients and to determine the variables associated with students'
      knowledge and attitudes towards them. BACKGROUND: Improving nurses' and nursing
      students' knowledge and attitudes towards patients with HIV/AIDS is vital for
      providing quality care for such patients. DESIGN: This descriptive, cross
      sectional study was conducted at three nursing schools located in two different
      cities in Turkey. The inclusion criteria for the nursing students were as
      follows: being at least 18 years old; being a first-, second-, third- or fourth
      year nursing student; and giving consent to participate in the research. METHODS:
      The sample comprised 580 nursing students. The study used three data collection
      tools: (1) the Student Socio-Demographic Questionnaire, (2) the HIV/AIDS
      Knowledge Questionnaire and (3) the HIV/AIDS Attitude Questionnaire. RESULTS:
      Participants' knowledge was found to be insufficient, particularly with regard to
      HIV transmission routes. They generally had positive attitudes towards patients
      with HIV/AIDS. However, they expressed some concerns and were hesitant about
      working with AIDS and HIV-positive patients. CONCLUSIONS: The current results
      reveal that nursing students still have misconceptions and a lack of knowledge of
      HIV/AIDS and that their attitudes need to be improved. RELEVANCE TO CLINICAL
      PRACTICE: Improving education programmes about HIV/AIDS and using information
      sources effectively may contribute to better knowledge and more desirable
      attitudes towards HIV/AIDS.

PMID- 24127907
TI  - Functional analysis of the rodent CK1tau mutation in the circadian clock of a
      marine unicellular alga.
AB  - BACKGROUND: Casein Kinase 1 (CK1) is one of few proteins known to affect cellular
      timekeeping across metazoans, and the naturally occurring CK1tau mutation
      shortens circadian period in mammals. Functional conservation of a timekeeping
      function for CK1 in the green lineage was recently identified in the green marine
      unicell Ostreococcus tauri, in spite of the absence of CK1's transcriptional
      targets known from other species. The short-period phenotype of CK1tau mutant in
      mammals depends specifically on increased CK1 activity against PERIOD proteins.
      To understand how CK1 acts differently upon the algal clock, we analysed the
      cellular and proteomic effects of CK1tau overexpression in O. tauri. RESULTS:
      Overexpression of the CK1tau in O. tauri induces period lengthening identical to
      overexpression of wild-type CK1, in addition to resistance to CK1 inhibitor
      IC261. Label-free quantitative mass spectrometry of CK1tau overexpressing algae
      revealed a total of 58 unique phospho-sites that are differentially responsive to
      CK1tau. Combined with CK1 phosphorylation site prediction tools and previously
      published wild-type CK1-responsive peptides, this study results in a highly
      stringent list of upregulated phospho-sites, derived from proteins containing
      ankyrin repeats, kinase proteins, and phosphoinositide-binding proteins.
      CONCLUSIONS: The identical phenotype for overexpression of wild-type CK1 and
      CK1tau is in line with the absence of critical targets for rodent CK1tau in O.
      tauri. Proteomic analyses reveal that two thirds of previously reported CK1
      overexpression-responsive phospho-sites are shared with CK1tau. These results
      indicate that the two alleles are functionally indiscriminate in O. tauri, and
      verify the identified cellular CK1 target proteins in a minimal circadian model
      organism.

PMID- 24127909
TI  - Selecting for function: solution synthesis of magnetic nanopropellers.
AB  - We show that we can select magnetically steerable nanopropellers from a set of
      carbon coated aggregates of magnetic nanoparticles using weak homogeneous
      rotating magnetic fields. The carbon coating can be functionalized, enabling a
      wide range of applications. Despite their arbitrary shape, all nanostructures
      propel parallel to the vector of rotation of the magnetic field. We use a simple
      theoretical model to find experimental conditions to select nanopropellers which
      are predominantly smaller than previously published ones. 

PMID- 24127910
TI  - Transcriptional and epigenetic modulation of human rhinovirus-induced CXCL10
      production by cigarette smoke.
AB  - Human rhinovirus (HRV) triggers exacerbations of asthma and chronic obstructive
      pulmonary disease. Cigarette smoking is the primary risk factor for the
      development of chronic obstructive pulmonary disease, and 25% of individuals with
      asthma smoke. Smokers experience both longer and more severe colds. We previously
      showed that cigarette smoke extract (CSE) inhibited HRV-induced expression of a
      range of epithelial antiviral molecules. Here, we use CXCL10 as a model antiviral
      gene to examine the mechanisms by which CSE inhibits epithelial antiviral
      immunity. HRV-induced CXCL10 transcription depends on activation of NF-KB and IFN
      regulatory factor-1 (IRF-1), and we now also implicate two signal transducer and
      activator of transcription (STAT) consensus sequences in the CXCL10 promoter in
      HRV-induced CXCL10 expression. CSE inhibited HRV-induced activation and nuclear
      translocation/binding of both NF-KB, and IRF-1 to their respective recognition
      sequences in the CXCL10 promoter. HRV also induced formation of complexes at the
      STAT region in the CXCL10 promoter, and HRV-induced activation of STAT-1 was
      inhibited by CSE. In addition, CSE inhibited HRV-induced chromatin accessibility
      around the transcriptional start site of the CXCL10 promoter. Although CSE
      inhibited HRV-induced expression of both the viral double-stranded RNA sensors,
      retinoic acid-inducible gene-I and melanoma differentiation-associated gene (MDA)
      5, only specific short interfering RNA (siRNA) to MDA5, but not nontargeting
      siRNA, or siRNA to retinoic acid-inducible gene-I, inhibited HRV-induced CXCL10
      induction. We conclude that CSE reduces chromatin accessibility and inhibits
      viral signaling via NF-KB, IRF-1, STAT-1, and MDA5. Thus, we show that CSE can
      simultaneously modulate multiple pathways linked to innate immune responses to
      HRV infection. 

PMID- 24127911
TI  - Two outbreaks of ESBL-producing Klebsiella pneumoniae in a neonatal intensive
      care unit.
AB  - BACKGROUND: In the present study, two epidemic episodes of extended spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae in the neonatal intensive care
      unit (NICU) were evaluated. METHODS: Routine and surveillance culture samples
      were taken from seven neonates with signs of infection in the NICU of Selcuk
      University Faculty of Medicine between 10 March and 25 April 2011, and between 11
      June and 30 September 2011. RESULTS: ESBL-producing K. pneumoniae strains were
      isolated in six different samples (one wound, one blood, and four cerebrospinal
      fluid cultures) of the three neonates in the first episode and in 11 different
      samples (seven blood and four cerebrospinal fluid cultures) of the four neonates
      in the second episode. ESBL-producing K. pneumoniae was isolated from inguinal,
      axillar region, and stool samples of the nine colonized neonates in the second
      episode. It was determined on pulse field gel electrophoresis that all strains
      originated from two clones. CONCLUSIONS: The deficiencies in the infection
      control measures in an NICU may transform into an epidemic rapidly. Therefore,
      periodic training, observation, and monitoring of compliance are important.

PMID- 24127913
TI  - Opioids in headache.
AB  - Opioid analgesics have long been used to treat head pain of various types. This
      has been increasing to a significant degree over the past 25 years because of a
      trend for more liberal use of opioids in non-malignant pain. Opioid treatment for
      acute headache, as well as prophylactically for refractory chronic headache, is
      controversial. There are a number of adverse effects associated with acute and
      chronic opioid treatment. Tolerance, dependence, and addiction are prominent
      issues. This article attempts to analyze the benefits and disadvantages for
      opioids in the management of migraine and other headache disorders, relying on
      known properties of this class of medication as well as clinical data. It will
      mainly focus on 2 topics: the use of opioid medication for the acute treatment of
      migraine attacks and continuous prophylactic use for refractory chronic migraine.

PMID- 24127914
TI  - Real world COPD: association of morning symptoms with clinical and patient
      reported outcomes.
AB  - This research examined the prevalence of morning symptoms and their relationship
      with health status, exacerbations and daily activity in patients with chronic
      obstructive pulmonary disease (COPD). Data on 1489 patients were analysed from a
      European and USA sample. Results were tested for significance (p < 0.05) using
      Mann-Whitney and regression modelling accounting for age, gender, body mass
      index, comorbidities, symptom severity, smoking status and medication adherence.
      Morning symptoms were experienced by 39.8% of patients. Controlling for potential
      confounders, morning symptoms were significantly associated with higher COPD
      assessment test scores (p < 0.001) and exacerbation frequency (p < 0.001), more
      frequent worsening of symptoms without consulting a Health Care Professional (p =
      0.008), and increased impact on normal daily activities (p = 0.007); and in the
      working population, a significantly greater impact on getting up and ready for
      the day (p < 0.001) and significantly more days off work per year (p < 0.001).
      Our research concluded that in patients with COPD, morning symptoms are
      associated with poorer health status, impaired daily activities and increased
      risk of exacerbation in affected patients compared with those patients without
      morning symptoms. Improved control of patients' morning symptoms may lead to
      substantial reduction in COPD impact and frequency of exacerbations, and enable
      patients to increase daily activities, particularly early morning activities.
      This could, in turn, enable working patients with COPD to be more productive in
      the workplace.

PMID- 24127915
TI  - Brachial plexus palsy after a left-side modified radical mastectomy with
      immediate latissimusdorsi flap reconstruction: report of a case.
AB  - Brachial plexus injury is a rare complication during operation and anesthesia; it
      can occur as a result of various mechanisms such as inappropriate positioning,
      over-abduction and stretching the upper limbs. Brachial plexus injury can cause
      the poor function of the upper limb before recovery, and sometimes serious injury
      is unable to completely recovered the function permanently. Here, we report a
      female breast cancer patient who sustained a left brachial plexus palsy after
      modified radical mastectomy with immediate breast reconstruction with
      latissimusdorsi flap (LDF). The patient had fully recovered with normal function
      of her left upper limb six months postoperation after conservative treatment.

PMID- 24127916
TI  - Genetics and preterm birth.
AB  - Although the etiology of preterm birth is incompletely understood, phenotype
      classifications combined with recent technologies such as genome-wide association
      studies and next-generation sequencing could lead to discovering genotypes
      associated with preterm birth. Identifying genetic contributions will allow for
      genetic screening tests to predict or detect pregnancies with potential for
      preterm birth. In this article we discuss current knowledge regarding phenotype
      classifications, genotypes, and their associations with preterm birth. 

PMID- 24127917
TI  - Improvements to direct quantitative analysis of multiple microRNAs facilitating
      faster analysis.
AB  - Studies suggest that patterns of deregulation in sets of microRNA (miRNA) can be
      used as cancer diagnostic and prognostic biomarkers. Establishing a "miRNA
      fingerprint"-based diagnostic technique requires a suitable miRNA quantitation
      method. The appropriate method must be direct, sensitive, capable of simultaneous
      analysis of multiple miRNAs, rapid, and robust. Direct quantitative analysis of
      multiple microRNAs (DQAMmiR) is a recently introduced capillary electrophoresis
      based hybridization assay that satisfies most of these criteria. Previous
      implementations of the method suffered, however, from slow analysis time and
      required lengthy and stringent purification of hybridization probes. Here, we
      introduce a set of critical improvements to DQAMmiR that address these technical
      limitations. First, we have devised an efficient purification procedure that
      achieves the required purity of the hybridization probe in a fast and simple
      fashion. Second, we have optimized the concentrations of the DNA probe to
      decrease the hybridization time to 10 min. Lastly, we have demonstrated that the
      increased probe concentrations and decreased incubation time removed the need for
      masking DNA, further simplifying the method and increasing its robustness. The
      presented improvements bring DQAMmiR closer to use in a clinical setting. 

PMID- 24127920
TI  - Training the translational research teams of the future: UC Davis-HHMI
      Integrating Medicine into Basic Science program.
AB  - There is a need for successful models of how to recruit, train, and retain bench
      scientists at the earliest stages of their careers into translational research.
      One recent, promising model is the University of California Davis Howard Hughes
      Medical Institute Integrating Medicine into Basic Science (HHMI-IMBS) program,
      part of the HHMI Med into Grad initiative. This paper outlines the HHMI-IMBS
      program's logic, design, and curriculum that guide the goal of research that
      moves from bedside to bench. That is, a curriculum that provides graduate
      students with guided translational training, clinical exposure, team science
      competencies, and mentors from diverse disciplines that will advance the students
      careers in clinical translational research and re-focusing of research to answer
      clinical dilemmas. The authors have collected data on 55 HHMI-IMBS students to
      date. Many of these students are still completing their graduate work. In the
      current study the authors compare the initial two cohorts (15 students) with a
      group of 29 control students to examine the program success and outcomes. The
      data indicate that this training program provides an effective, adaptable model
      for training future translational researchers. HHMI-IMBS students showed improved
      confidence in conducting translational research, greater interest in a future
      translational career, and higher levels of research productivity and
      collaborations than a comparable group of predoctoral students. 

PMID- 24127921
TI  - Differential gene expression reveals mitochondrial dysfunction in an imprinting
      center deletion mouse model of Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder caused by deficiency of
      imprinted gene expression from the paternal chromosome 15q11-15q13 and clinically
      characterized by neonatal hypotonia, short stature, cognitive impairment,
      hypogonadism, hyperphagia, morbid obesity, and diabetes. Previous clinical
      studies suggest that a defect in energy metabolism may be involved in the
      pathogenesis of PWS. We focused our attention on the genes associated with energy
      metabolism and found that there were 95 and 66 mitochondrial genes differentially
      expressed in PWS muscle and brain, respectively. Assessment of enzyme activities
      of mitochondrial oxidative phosphorylation complexes in the brain, heart, liver,
      and muscle were assessed. We found the enzyme activities of the cardiac
      mitochondrial complexes II+?III were up-regulated in the PWS imprinting center
      deletion mice compared to the wild-type littermates. These studies suggest that
      differential gene expression, especially of the mitochondrial genes may
      contribute to the pathophysiology of PWS.

PMID- 24127922
TI  - Researching together: a CTSA partnership of academicians and communities for
      translation.
AB  - BACKGROUND: The Colorado Clinical and Translational Sciences Institute (CCTSI)
      aims to translate discovery into clinical practice. The Partnership of
      Academicians and Communities for Translation (PACT) represents a robust campus
      community partnership. METHODS: The CCTSI collected data on all PACT activities
      including meeting notes, staff activity logs, stakeholder surveys and interviews,
      and several key component in-depth evaluations. Data analysis by Evaluation and
      Community Engagement Core and PACT Council members identified critical shifts
      that changed the trajectory of community engagement efforts. RESULTS: Ten
      "critical shifts" in six broad rubrics created change in the PACT. Critical
      shifts were decision points in the development of the PACT that represented
      quantitative and qualitative changes in the work and trajectory. Critical shifts
      occurred in PACT management and leadership, financial control and resource
      allocation, and membership and voice. DISCUSSION: The development of a campus
      community partnership is not a smooth linear path. Incremental changes lead to
      major decision points that represent an opportunity for critical shifts in
      developmental trajectory. We provide an enlightening, yet cautionary, tale to
      others considering a campus-community partnership so they may prepare for crucial
      decisions and critical shifts. The PACT serves as a genuine foundational platform
      for dynamic research efforts aimed at eliminating health disparities.

PMID- 24127923
TI  - Research participation by low-income and racial/ethnic minority groups: how
      payment may change the balance.
AB  - Minorities are underenrolled in clinical research trials, and one-third of trials
      are underenrolled overall. The role of payment has not been studied at the
      national level as an explanation for enrollment patterns. Our objective was to
      examine the distribution of self-reported previous research participation across
      different sociodemographic groups; to assess the public's perception of fair
      payment for a low-risk medicine trial and the association between requested
      payment and sociodemographic characteristics; to estimate the amount of payment
      for a medication trial to achieve proportional representation of minorities and
      different socioeconomic groups. This was a cross-sectional study with nationally
      representative data collected in 2011 by the C.S. Mott Children's Hospital
      National Poll on Children's Health. To determine the relationship between
      perceived fair payment and individual-level characteristics, we used
      multivariable linear regression. With 60% participation rate, in a sample of
      2,150 respondents 11% (n = 221) of the sample had previously participated in
      medical research. Requested payment differed significantly by racial/ethnic group
      with Hispanics requesting more payment than non-Hispanic whites (0.37 [95%CI
      0.02, 0.72]) In contrast to payment at $49, $149, and $249, payment at $349
      yielded proportional representation of racial/ethnic minority groups. Hispanics
      requested higher payment for research participation, suggesting a possible
      explanation for their underenrollment.

PMID- 24127924
TI  - Effect of hydrogen-rich water on oxidative stress, liver function, and viral load
      in patients with chronic hepatitis B.
AB  - OBJECTIVE: To investigate effects of hydrogen-rich water (HRW) on oxidative
      stress, liver function and HBV DNA in patients with chronic hepatitis B (CHB).
      METHODS: Sixty patients with CHB were randomly assigned into routine treatment
      group or hydrogen treatment group in which patients received routine treatment
      alone or additional oral HRW (1200-1800 mL/day, twice daily), respectively, for 6
      consecutive weeks. Serum oxidative stress, liver function, and HBV DNA level were
      detected before and after treatment. Thirty healthy subjects served as controls.
      RESULTS: When compared with controls, oxidative stress was obvious in CHB
      patients, and the liver function also significantly impaired. After treatment,
      the oxidative stress remained unchanged in routine treatment group, but markedly
      improved in hydrogen treatment group. The liver function was improved
      significantly and the HBV DNA reduced markedly after corresponding treatments.
      Although a significant difference was noted in the oxidative stress between two
      groups after treatment, the liver function and HBV DNA level were comparable
      after treatment and both had improved tendencies. CONCLUSION: HRW significantly
      attenuates oxidative stress in CHB patients, but further study with long-term
      treatment is required to confirm the effect of HRW on liver function and HBV DNA
      level.

PMID- 24127925
TI  - Mentor training within academic health centers with Clinical and Translational
      Science Awards.
AB  - Multiple studies highlight the benefits of effective mentoring in academic
      medicine. Thus, we sought to quantify and characterize the mentoring practices at
      academic health centers (AHCs) with Clinical and Translational Science Awards
      (CTSA). Here we report findings pertaining specifically to mentor training at the
      level of the KL2 mentored award program, and at the broader institutional level.
      We found only four AHCs did not provide any form of training. One-time
      orientation was most prevalent at the KL2 level, whereas formal face-to-face
      training was most prevalent at the institutional level. Despite differences in
      format usage, there was general consensus at both the KL2 and institutional level
      about the topics of focus of face-to-face training sessions. Lower-resource
      training formats utilized at the KL2 level may reveal a preference for
      preselection of qualified mentors, while institutional selection of resource
      heavy formats may be an attempt to raise the mentoring qualifications of the
      academic community as a whole. The present work fits into the expanding landscape
      of academic mentoring literature and sets the framework for future longitudinal,
      outcome studies focused on identifying the most efficient strategies to develop
      effective mentors. 

PMID- 24127926
TI  - Different cellular localization of NF-kappaB p65 expression as an indicator of
      different prognoses of stage I-III gastric cancer patients.
AB  - BACKGROUND: Nuclear factor-kappaB p65 (NF-kappaB p65) may play a significant role
      as a biomarker in tumor progression and metastasis. However, the correlation
      between cellular localization of NF-kappaB p65 expression and the prognosis of
      gastric cancer (GC) patients has not been studied. The present study was designed
      to investigate the location of NF-kappaB p65 expression in GC, and evaluate its
      correlation with clinicopathological parameters of GC patients. METHODS: NF
      kappaB p65 expressions in GC tissue and corresponding nonmalignant tissue from
      gastrectomy of 115 stage I-III GC patients were detected by immunohistochemistry.
      In addition, correlations between the staining results and the clinicopathologic
      features and survival of the GC patients were analyzed. RESULTS: The percentage
      of NF-kappaB p65 expression in GC tissue and the corresponding nonmalignant
      tissue was 73.9% and 46.80%, respectively. No significant correlation was found
      between NF-kappaB p65 expression and the clinicopathologic parameters. Cox
      univariate analysis indicated that both nuclear staining and cytoplasmic staining
      of NF-kappaB p65 expression correlated with the prognosis of GC patients (log
      rank, p = 0.0182; p = 0.0144, respectively). CONCLUSION: High nuclear expression
      of NF-kappaB p65 is an independent prognostic marker predicting a better
      survival, while high cytoplasmic staining indicates a worse prognosis of GC
      patients.

PMID- 24127927
TI  - Initiation of aspirin therapy modulates angiogenic protein levels in women with
      breast cancer receiving tamoxifen therapy.
AB  - Aspirin has a range of antineoplastic properties linked to inhibition of
      cyclooxygenase enzymes in tumor cells, platelet inhibition and to inhibition of
      angiogenesis. We undertook a prospective study to determine the influence of a 45
      day course of aspirin therapy on circulating and intraplatelet levels of selected
      proangiogenic (vascular endothelial growth factor [VEGF]) and antiangiogenic
      (thrombospondin-1 [TSP-1]) proteins, and platelet protein release in women
      diagnosed with breast cancer who were receiving tamoxifen therapy. Initiation of
      aspirin therapy increases serum and intraplatelet levels of TSP-1 without a
      corresponding increase in VEGF levels. Following aspirin therapy, VEGF levels
      decreased (relative to pretreatment levels) while TSP-1 returned to pretreatment
      levels. Plasma TSP-1 and VEGF levels did not change on aspirin therapy. Aspirin
      use also decreased thrombin receptor mediated release of TSP-1 and VEGF from
      platelets. The selective impact on platelet angiogenic protein content and
      release supports one mechanism by which aspirin can modify the angiogenic balance
      in women receiving tamoxifen therapy. Aspirin therapy appears to favor an overall
      antiangiogenic balance in women with breast cancer who are receiving tamoxifen
      therapy. 

PMID- 24127928
TI  - Assessing research interest and capacity in community health centers.
AB  - OBJECTIVE: Community health centers (CHCs) have great potential to participate in
      the development of evidence-based primary care but face obstacles to engagement
      in clinical translational research. METHODS: To understand factors associated
      with CHC interest in building research infrastructure, Harvard Catalyst and the
      Massachusetts League of Community Health Centers conducted an online survey of
      medical directors in all 50 Massachusetts CHC networks. RESULTS: Thirty-two (64%)
      medical directors completed the survey representing 126 clinical sites. Over 80%
      reported that their primary care providers (PCPs) were slightly to very
      interested in future clinical research and that they were interested in building
      research infrastructure at their CHC. Frequently cited barriers to participation
      in research included financial issues, lack of research skills, and lack of
      research infrastructure. In bivariate analyses, PCP interest in future clinical
      research and a belief that involvement in research contributed to PCP retention
      were significantly associated with interest in building research infrastructure.
      CONCLUSION: CHCs critical role in caring for vulnerable populations ideally
      positions them to raise relevant research questions and translate evidence into
      practice. Our findings suggest a high interest in engagement in research among
      CHC leadership. CTSAs have a unique opportunity to support local CHCs in this
      endeavor.

PMID- 24127929
TI  - Construction of a US fibromyalgia registry using the Fibromyalgia Research Survey
      criteria.
AB  - Utilizing billing records, we identified patients seen at Mayo Clinic with a
      diagnosis or history of fibromyalgia who were then contacted for enrollment in a
      fibromyalgia research registry. Fibromyalgia was confirmed through medical record
      review. Eligible patients were mailed an invitation that included a demographic
      questionnaire and the Fibromyalgia Research Survey. The Fibromyalgia Research
      Survey yields a widespread pain score (scale range 0-19) and a symptom severity
      score (scale range 0-12). A total of 4,034 patients returned the completed
      survey; 92.8% were female, their mean age was 57.4 (+/-13.4), and 83.7% were from
      the Midwest region of the United States. The mean widespread pain score for all
      participants was 11.3 (+/-4.5) and the mean symptom severity score was 8.2 (+/
      2.4), indicating moderate-to-severe fibromyalgia symptoms, which is not unusual
      for patients presenting to a tertiary care center. Using a systematic process, we
      describe the creation of a fibromyalgia registry for future research. 

PMID- 24127930
TI  - Catechol-O-methyltransferase genotype modulates opioid release in decision
      circuitry.
AB  - Impulsivity, a risk factor for substance abuse disorders, is modulated by the
      Val158 variant of the catechol-O-methyltransferase (COMT) gene. Rodent studies
      have shown that opioids enhance impulsivity. Furthermore, alcohol consumption
      leads to endogenous opioid release in the cortex and nucleus accumbens (NAc), and
      this opioid release is correlated with greater positive hedonic effect. Using the
      selective mu opioid receptor radioligand [11C] carfentanil, we find that,
      following alcohol consumption, individuals with the COMT Val158 allele have
      greater opioid release in the right NAc but less release in medial orbital
      frontal cortex (OFC). These data suggest that genetic regulation of dopamine
      levels can affect alcohol consumption in part by modulating endogenous opioid
      release in specific brain regions implicated in reward, which in turn promotes
      impulsive choice.

PMID- 24127931
TI  - Provider's perspectives on building research and quality improvement capacity in
      primary care: a strategy to improve workforce satisfaction.
AB  - OBJECTIVES: Safety-net populations are underrepresented in research and quality
      improvement (QI) studies despite the fact that safety-net providers are uniquely
      positioned to engage in translational research. This study aimed to understand
      the current level of interest in, experience with, predicted career satisfaction
      associated with, and barriers experienced in conducting research and QI among
      primary care providers (PCPs) at 18 safety-net practices in the Boston,
      Massachusetts area. METHODS: The Harvard Catalyst Safety-net Infrastructure
      Initiative partnered with staff at a large academic public hospital system,
      including 15 primary care sites, to develop and administer an online survey. This
      survey was then adapted and administered at three other academically affiliated
      community health centers. RESULTS: Of the 260 providers surveyed, 136 (52%)
      responded. Nearly 80% reported interest in conducting either QI projects or
      clinical research and 95% of them believed it would enhance their career
      satisfaction. However, 63% did not report prior experience or training in
      research or QI and 93% reported at least one barrier to engagement. CONCLUSION:
      While supporting safety-net PCPs' engagement in research and/or QI may improve
      career satisfaction there are numerous barriers that must be addressed to achieve
      this goal.

PMID- 24127932
TI  - Drug design and discovery: translational biomedical science varies among
      countries.
AB  - Drug design and discovery is an innovation process that translates the outcomes
      of fundamental biomedical research into therapeutics that are ultimately made
      available to people with medical disorders in many countries throughout the
      world. To identify which nations succeed, exceed, or fail at the drug
      design/discovery endeavor--more specifically, which countries, within the context
      of their national size and wealth, are "pulling their weight" when it comes to
      developing medications targeting the myriad of diseases that afflict humankind-
      we compiled and analyzed a comprehensive survey of all new drugs (small molecular
      entities and biologics) approved annually throughout the world over the 20-year
      period from 1991 to 2010. Based upon this analysis, we have devised prediction
      algorithms to ascertain which countries are successful (or not) in contributing
      to the worldwide need for effective new therapeutics.

PMID- 24127933
TI  - Strategies for mentor matching: lessons learned.
AB  - Mentoring serves to guide early stage researchers toward opportunities which can
      further their careers. The most beneficial mentoring experience occurs when both
      the mentor and mentee share a common background and have appropriate
      expectations. Our CTSA serves individuals in a five state region with widely
      disparate needs and we have often struggled to provide appropriate guidance for
      those requesting mentoring services. Here we present an overview of our past
      mentor identification strategy along with a proposed new direction to increase
      flexibility, sustainability and better serve researchers in our region. 

PMID- 24127935
TI  - h-BN monolayer on the Ni(111) surface: a potential catalyst for oxidation.
AB  - The hexagonal boron nitride (h-BN) is traditionally considered to be inert. In
      sharp contrast to the inert behavior of free-standing hexagonal boron nitride (h
      BN), we propose the catalytic property of h-BN monolayer on Ni(111) substrate
      using first-principles density functional theory investigation. The interaction
      of O2 molecule with the h-BN/Ni(111) substrate results in nondissociative
      adsorption of the molecule along with elongation of the O-O bond. This can be
      considered as the activated state of the O2 molecule. Further interaction of this
      complex viz O2-h-BN/Ni(111) with an incoming CO molecule leads to the spontaneous
      formation of CO2. Interestingly, the CO adsorption on the h-BN/Ni(111) substrate
      was found to be unfavorable, thereby implying the oxidation of CO selectively
      through Eley-Rideal (ER) mechanism. 

PMID- 24127937
TI  - Lessons learned and challenges posed in cancer genetics. Introduction.

PMID- 24127938
TI  - Telomeres and human health.
AB  - Telomeres are the tips of chromosomes and consist of proteins and hexanucleotide
      tandem repeats of DNA. The DNA repeats are shortened at each mitotic division of
      normal cells, and the telomere length chronicles how many divisions the cell has
      undergone. Thus, telomere length is a marker of fundamental biological pathways.
      It has been possible to measure telomere length for more than 20 years, and it
      has been established that telomere length is associated with age, sex and
      lifestyle factors. Here, the current knowledge of telomere length as a biomarker
      of disease susceptibility and mortality will be reviewed. In addition, technical
      difficulties and the reasons why measurement of telomeres has still not been
      introduced into routine clinical practice will be discussed. Findings from recent
      studies conducted in many thousands of individuals indicate that telomere length
      is not-or at best only marginally-independently associated with risk of common
      disorders such as cardiovascular, pulmonary and neoplastic diseases. However, in
      sufficiently powered studies, short telomeres are repeatedly and independently
      found to be associated with increased risk of early death in the general
      population or in subsets of individuals. This indicates that measurement of
      telomeres could be a valuable prognostic biomarker in many clinical settings.
      However, whether short telomeres are a causal factor for or simply a marker of
      increased risk of early death must be determined. Finally, how Mendelian
      randomization studies could clarify this issue, and which clinical studies might
      be carried out to refine this very promising biomarker for routine clinical use
      will be considered. 

PMID- 24127939
TI  - Lessons from postgenome-wide association studies: functional analysis of cancer
      predisposition loci.
AB  - In the last few years, genome-wide association studies (GWASs) have identified
      hundreds of predisposition loci for several types of human cancers. Recent
      progress has been made in determining the underlying mechanisms through which
      different single-nucleotide polymorphisms (SNPs) affect predisposition to cancer.
      Although there has been much debate about the clinical utility of GWASs, less
      attention has been paid to how GWASs and post-GWASs functional analysis have
      contributed to understanding the aetiology of cancer. Most common variants
      associated with cancer risk are localized in nonprotein-coding regions
      highlighting transcriptional regulation as a common theme in the mechanism of
      cancer predisposition. Here, we outline strategies to functionally dissect
      predisposition loci and discuss their limitations as well as challenges for
      future studies. 

PMID- 24127940
TI  - Identification of biomarkers for apoptosis in cancer cell lines using
      metabolomics: tools for individualized medicine.
AB  - BACKGROUND: Metabolomics is a versatile unbiased method to search for biomarkers
      of human disease. In particular, one approach in cancer therapy is to promote
      apoptosis in tumour cells; this could be improved with specific biomarkers of
      apoptosis for monitoring treatment. We recently observed specific metabolic
      patterns in apoptotic cell lines; however, in that study, apoptosis was only
      induced with one pro-apoptotic agent, staurosporine. OBJECTIVE: The aim of this
      study was to find novel biomarkers of apoptosis by verifying our previous
      findings using two further pro-apoptotic agents, 5-fluorouracil and etoposide,
      that are commonly used in anticancer treatment. METHODS: Metabolic parameters
      were assessed in HepG2 and HEK293 cells using the newborn screening assay adapted
      for cell culture approaches, quantifying the levels of amino acids and
      acylcarnitines with mass spectrometry. RESULTS: We were able to identify
      apoptosis-specific changes in the metabolite profile. Moreover, the amino acids
      alanine and glutamate were both significantly up-regulated in apoptotic HepG2 and
      HEK293 cells irrespective of the apoptosis inducer. CONCLUSION: Our observations
      clearly indicate the potential of metabolomics in detecting metabolic biomarkers
      applicable in theranostics and for monitoring drug efficacy.

PMID- 24127941
TI  - Public health genomics and personalized prevention: lessons from the COGS
      project.
AB  - Using the principles of public health genomics, we examined the opportunities and
      challenges of implementing personalized prevention programmes for cancer at the
      population level. Our model-based estimates indicate that polygenic risk
      stratification can potentially improve the effectiveness and cost-effectiveness
      of screening programmes. However, compared with 'one-size-fits-all' screening
      programmes, personalized screening adds further layers of complexity to the
      organization of screening services and raises ethical, legal and social
      challenges. Before polygenic inheritance is translated into population screening
      strategy, evidence from empirical research and engagement with and education of
      the public and the health professionals are needed. 

PMID- 24127942
TI  - Why is it so difficult to identify a single indicator of water stress in plants?
      A proposal for a multivariate analysis to assess emergent properties.
AB  - Because of the complexity of plant responses to water deficit, researchers have
      attempted to identify simplified models to understand critical aspects of the
      problem by searching for single indicators that would enable evaluations of the
      effects of environmental changes on the entire plant. However, this reductionist
      approach, which is often used in plant sciences, makes it difficult to
      distinguish systemic emergent behaviours. Currently, a new class of models and
      epistemology have called attention to the fundamental properties of complex
      systems. These properties, termed 'emergent', are observed at a large scale of
      the system (top hierarchical level) but cannot be observed or inferred from
      smaller scales of observation in the same system. We propose that multivariate
      statistical analysis can provide a suitable tool to quantify global responses to
      water deficit, allowing a specific and partially quantitative assessment of
      emergent properties. Based on an experimental study, our results showed that the
      classical approach of the individual analysis of different data sets might
      provide different interpretations for the observed effects of water deficit.
      These results support the hypothesis that a cross-scale multivariate analysis is
      an appropriate method to establish models for systemic understanding of the
      interactions between plants and their changing environment.

PMID- 24127944
TI  - Vulva or Aidoio: Latin or Greek but avoid hybrid terms.

PMID- 24127943
TI  - A critical appraisal of complications of percutaneous nephrolithotomy in
      paediatric patients using adult instruments.
AB  - OBJECTIVE: To evaluate the complications (using the CROES Clavien scoring system)
      and various factors affecting them in children undergoing percutaneous
      nephrolithotomy (PCNL). PATIENTS AND METHODS: We analysed prospectively
      maintained data of paediatric PCNL (patients <=17 years) from January 2008 to
      December 2012. Stone complexity was defined according to validated Guy's stone
      score (GSS). Procedures were performed in the prone position by experienced
      urologists. The tract was dilated (24-30F) under fluoroscopic guidance, and an
      adult rigid nephroscope complemented with a cystoscope/ureteroscope were used.
      Complications were recorded according to the CROES-Clavien score, recently
      defined by the Clinical Research Office of the Endourological Society (CROES)
      Study Group. RESULTS: The study group comprised 158 procedures performed in 153
      children (98 boys and 55 girls), with a mean (range) age 10.03 +/- 4.51 (2-17)
      years. The mean (range) stone burden was 376.68 +/- 265.23 (150-2400) mm(2) . The
      distribution of cases according to the GSS was 31% grade I, 35.4% grade II, 19%
      grade III, and 14.6% grade IV. The stone-free rate of PCNL monotherapy was 85.4%,
      which increased to 93.7% after relook PCNL/extracorporeal shock wave lithotripsy.
      In all, 62 children (39.2%) had operative complications; 84% were minor, i.e.
      Clavien grade 1/2, and managed conservatively. Stone size, GSS, tract size,
      number of punctures and operation duration were significantly associated with
      complications on univariate analysis (P < 0.05). However, on multivariate
      logistic regression analysis, operation duration was the only independent risk
      factor associated with complications (95% confidence interval: 1.013-1.065, odds
      ratio = 1.04; P = 0.038). CONCLUSIONS: Percutaneous nephrolithotomy in children
      using adult instruments is an effective and safe procedure for managing simple as
      well as complex renal calculi. Assignment of specific Clavien scores to all
      possible PCNL complications by the CROES PCNL Study Group have improved precision
      in reporting complications in a standard objective format, including the minor
      ones. Such models are very useful for making inter-observer comparisons to obtain
      clinically relevant inferences. Mean operation duration is the only independent
      factor affecting complications of the procedure.

PMID- 24127945
TI  - The normal vulva in medical textbooks.
AB  - When a healthy woman expresses concerns about her vulva, the doctor's response
      should be informed by clinical knowledge. For many doctors, accumulation of such
      knowledge would have begun with undergraduate teaching and medical textbooks. The
      aim of this study is to examine the information on female genital morphology in
      medical textbooks. A total of 59 gynaecology and anatomy textbooks were searched
      for information on the dimensions of vulval constitutent parts. No textbook gave
      measurements for all vulval structures. Vaginal length was reported in 21/59
      textbooks, clitoral size in 15/59 and labia minora in 1/59. Where measurements
      appear, they suggest narrower ranges than recent reports. Information of vulval
      morphology is scanty and inaccurate in medical textbooks. The general lack of
      professional resources means that doctors may consciously or non-consciously rely
      upon personal experiences and popular culture to form their opinions, as do their
      patients. 

PMID- 24127946
TI  - Terminology and diagnosis of vulval pain.
AB  - Accurate terminology to allow meaningful understanding of aetiology, diagnosis
      and management of vulval pain continues to evolve. The most recent classification
      has been endorsed by the International Society for the Study of Vulvovaginal
      Disease, and is discussed. In theory, we should replace 'vulvodynia' by
      'aidoiodynia', as per this issue's associated Editorial. 

PMID- 24127947
TI  - Perioperative morbidity associated with abdominal myomectomy compared with total
      abdominal hysterectomy for uterine fibroids.
AB  - The aim of the study was to systematically review and summarise existing evidence
      related to the perioperative morbidity associated with abdominal myomectomy in
      comparison with abdominal hysterectomy for uterine fibroids. A review of MEDLINE
      and EMBASE was carried out. The primary outcome was the major morbidity rate and
      secondary outcomes were uterine size, estimated blood loss, blood transfusion,
      operating time and duration of hospital stay. The results identified six
      observational studies including 1520 participants. All studies scored moderately
      on the N-OQA scale and were limited to a uterine size of up to 18 weeks. There
      was no significant difference in the rate of major morbidity (RR 0.94; 95% CI =
      0.31, 2.81; p = 0.91) between the two operations. It was concluded that based on
      variable quality data from retrospective cohort studies, abdominal myomectomy and
      hysterectomy appear to have similar major morbidity rates for the uterine size up
      to 16-18 weeks. Well-designed trials with a standardised morbidity outcome and
      including uterine size greater than 18 weeks are required. 

PMID- 24127948
TI  - Fibrochondrogenesis: prenatal diagnosis and outcome.
AB  - We studied 20 cases with fibrochondrogenesis (FCG) diagnosed prenatally. Four
      cases were diagnosed at our fetal unit, and 16 cases were identified through a
      review of literature (in English). The prenatal diagnosis of FCG was made in 4/20
      (20%). Six (30%) patients opted for termination of pregnancy (TOP). A total of 13
      cases delivered at term. Four (30.8%) had a caesarean section. Four neonates
      (30.7%) were stillborn and seven (53.8%) neonates died within 3 months. Two
      infants survived beyond 3 years of age, but both had severe global developmental
      delay. A molecular study of the surviving children revealed two null homozygous
      mutations in COL11A1 [c.4084C > T (p.R1362X) and c.3708 + c.437T > G]. We
      concluded that the prenatal diagnosis of fibrochondrogenesis is feasible.
      Fibrochondrogenesis is usually a fatal disease and survivors suffer from severe
      physical and neurological impairment. 

PMID- 24127949
TI  - Hydatoxi lualba: the worm that wasn't!
AB  - Pre-eclampsia is a disorder that occurs only during pregnancy and the postpartum
      period and affects both the mother and the unborn child. Affecting at least 5-8%
      of all pregnancies, it can be a rapidly progressive condition characterised by
      hypertension and proteinuria. Oedema, sudden weight gain, headaches and changes
      in vision are important symptoms. However, some women with rapidly advancing
      disease report few symptoms. 

PMID- 24127950
TI  - Maternal obesity and gestational weight gain.
AB  - The aim of the study was to analyse gestational weight gain (GWG) according to
      body mass index (BMI) category and to explore the relationship between GWG and
      pregnancy complications. Women were recruited in the 1st trimester. Weight and
      height were measured and BMI calculated. Weight was measured at 38 weeks'
      gestation and GWG calculated. Clinical details were obtained prospectively. Of
      the 604 women recruited, 45.5% were primigravidas and 25.2% were obese. The
      overall mean GWG was 11.6 kg (SD 6.0). In obese women, the mean GWG was 10.4 kg
      (SD 7.5) compared with 12.6 kg (SD 5.7) in the normal BMI category (p < 0.001).
      Maternal obesity but not increased GWG was associated with an increased risk of
      induction of labour, caesarean section and pre-eclampsia. It was concluded that
      obese women were more likely to exceed GWG recommendations, despite lower GWG
      than non-obese women. Maternal obesity and not GWG increased the risk of
      pregnancy complications. 

PMID- 24127951
TI  - Ultrasound management and clinical outcome of twin pregnancies.
AB  - The rate of multiple pregnancies is showing a significant increase in Western
      countries. Twin gestations should be considered a high-risk condition because
      they are responsible for a disproportionate amount of overall perinatal morbidity
      and mortality. We used a specialised ultrasound protocol based on chorionicity to
      monitor 44 twin pregnancies (61% dichorionic diamniotic (DD) and 39%
      monochorionic diamniotic (MD)). Adverse pregnancy outcomes and pre-term
      deliveries were more common in MD pregnancies than in DD pregnancies; the rate of
      extreme pre-term delivery (< 32 weeks) was almost three-times higher in MD than
      in DD pregnancies (41% vs 15%) and perinatal complications were more frequent in
      MD than in DD pregnancies (59% vs 22%), but fetal anomalies were more frequent in
      DD than in MD pregnancies (30% vs 24%). Periodic ultrasound follow-up would
      predict the pregnancies that are at greater risk for fetal and neonatal
      complications and these should be monitored more closely. 

PMID- 24127952
TI  - Progesterone use after successful treatment of threatened pre-term delivery.
AB  - Pre-term delivery is the leading cause of neonatal morbidity, mortality and long
      term sequels. This is an open label randomised controlled trial with women with
      confirmed threatened pre-term labour (TPTL) after efficient tocolytic therapy
      with atosiban. The main outcome measure of this study was the latency period
      until delivery and secondary outcomes were the number of recurrent episodes of
      TPTL and fetal and maternal morbidity. Patients were assigned to treatment or
      control groups using a computer generated randomisation table. The treatment
      group received 200 mg vaginal progesterone daily until delivery and the control
      group received no therapy or placebo. The study cohort comprised 52 pregnant
      women, 26 in each arm, showing similar characteristics; the treatment group had a
      longer latency period until delivery and this was statistically significant (55
      vs 38 days, p = 0.024). This study points to the benefits of the vaginal
      administration of progesterone, especially in prolonging latency period until
      delivery. 

PMID- 24127953
TI  - Transabdominal cerclage placement in patients with prior uterine incisions: risk
      of scar disruption.
AB  - The object of this study was to describe pregnancy outcomes in women who had a
      transabdominal cerclage (TAC) placed after a prior uterine incision due to
      caesarean section or hysterotomy. This is a retrospective observational study of
      57 women referred to a maternal-fetal medicine specialist (JES) for TAC placement
      after a previous uterine incision from 1989-2012. Pregnancy outcomes post-TAC
      placement are reported, including gestational age at delivery, survival rate and
      complications directly related to labour and the previous uterine scar. Of 51
      women who had a prior uterine incision and were pregnant at TAC, 49 (96.1%)
      delivered viable infants at a mean gestational age of 35.9 weeks. One patient had
      intrauterine fetal demise at 16 weeks for causes likely unrelated to TAC and
      another had uterine rupture associated with a unicornuate uterus and advancing
      labour at 31 weeks. This study includes women with low transverse incisions,
      classical uterine incisions and higher order multiples. It was concluded that in
      women with a prior uterine incision, placement of a TAC is associated with low
      risk (2%) of uterine rupture. 

PMID- 24127954
TI  - Impact of fetal pulse oximetry and ST analysis surveillance withdrawal on rates
      of obstetric surgery and frequency of low birth umbilical artery pH: a cause of
      rising caesarean rates?
AB  - A retrospective observational study on a sample of 13,413 deliveries analysed the
      effect of a withdrawal of the CTG additional diagnostic methods of fetal hypoxia
      (fetal pulse oximetry and ST analysis of the fetal ECG) on operative delivery
      rates and frequency of the umbilical arterial pH < 7.15. Following the
      withdrawal, obstetricians are more likely to perform caesarean sections for fetal
      hypoxia (OR 2.23, 95% CI 1.94-2.55, p < 0.0001) and labour dystocia (OR 1.45, 95%
      CI 1.18-1.77, p = 0.0003), which increases the overall caesarean rate (OR 1.49,
      95% CI 1.38-1.61, p < 0.0001), although decreases the incidence of birth
      umbilical arterial pH < 7.15 (OR 0.43, 95% CI 0.22-0.85, p = 0.015). This also
      leads to the significant decline in overall frequency of instrumental vaginal
      deliveries (OR 0.58, 95% CI 0.48-0.71). In order to decrease the overall
      caesarean rate, obstetricians need to be supported by more accurate and possibly
      automated diagnostic tools for intrapartum fetal hypoxia. 

PMID- 24127955
TI  - Assessment of interdisciplinary communication for Category 1 caesarean sections.
AB  - We assessed how often the urgency of Category 1 caesarean sections was
      incorrectly recorded by the anaesthetic and theatre teams. Category 1 caesarean
      sections were identified over a 15-month period (September 2010 to November
      2011), from the daily audit of emergency caesarean sections undertaken by the
      obstetric team. The categories of urgency as recorded by the attending
      anaesthetist and theatre team were noted for each case. There were 236 Category 1
      caesarean sections identified, of which 47 were incorrectly recorded as Category
      2 by either the anaesthetist alone (34), the theatre team alone (1) or both (12).
      Where the category of urgency was correctly recorded, 11.6% of cases had a
      decision-to-delivery interval of more than 30 min compared with 27.7% of cases
      recorded as Category 2 (p = 0.01, Fisher's exact test). 

PMID- 24127956
TI  - Quantification of risk of emergency caesarean during labour after one previous
      caesarean section.
AB  - In its 2007 guideline, the Royal College of Obstetricians and Gynaecologists
      (RCOG) recommends vaginal birth after caesarean (VBAC) as safer than repeat
      elective caesarean sections. However, this document does not give details of risk
      of emergency caesarean section for women accepting VBAC. An emergency caesarean
      is associated with increased maternal and neonatal morbidity, and women do
      consider the eventuality of emergency delivery when deciding mode of delivery. We
      sought to quantify this risk by designing a retrospective cohort study in a
      consultant-led unit. While higher than average rates of successful planned VBAC
      were achieved, the odds of emergency caesarean delivery were increased in women
      undergoing VBAC (OR 3.0, 95% CI 1.2-7.6, p = 0.03). Odds of requiring a Category
      1 emergency caesarean were markedly raised. Our data adds to the VBAC literature
      by quantifying the risk of Category 1 or 2 emergency caesarean section for women
      entering labour who have delivered by caesarean section once previously, giving
      the odds of emergency caesarean section on entering labour compared with women
      without a scar. This gives further information to those counselling women about
      birth after caesarean section. 

PMID- 24127957
TI  - Effect of early skin-to-skin contact on breast-feeding.
AB  - We examined the effect of early skin-to-skin contact (SSC) on breast-feeding at 1
      month after delivery, in Japanese women. We reviewed the obstetric records of
      healthy nulliparous women with vaginal singleton delivery at 37-41 weeks'
      gestation, at the Japanese Red Cross Katsushika Maternity Hospital and between 1
      February and 30 November 2011, there was a total of 403 women who planned to
      breast-feed their babies at birth. Of these, 272 women (67.5%) initiated early
      SSC in the delivery room and 131 women (32.5%) did not initiate early SSC. There
      were no significant differences in the obstetric characteristics and birth
      outcomes between the two groups of women with and without initiating early SSC.
      However, the rate of exclusive breast-feeding at 1 month after delivery in the
      group of women following early SSC (59.6%, 162/272) was significantly higher than
      that in the group of women without early SSC (45.8%, 60/131; crude OR 1.74, 95%
      CI 1.1-2.7, p = 0.009). The current results may support the benefit of early SSC
      in Japanese women after vaginal delivery. 

PMID- 24127958
TI  - Factors influencing the outcome of intrauterine insemination (IUI): age, clinical
      variables and significant thresholds.
AB  - The aim was to investigate the influence of various biological factors upon the
      outcome of intrauterine insemination (IUI). The total IUI history (856 cycles) of
      352 couples was studied. Live-birth showed a strong negative correlation with
      female age but no correlation with male age. Antimullerian hormone (AMH) and
      antral follicle count (AFC) correlated negatively with female age, and follicle
      stimulating hormone (FSH) correlated positively. Significant thresholds were
      found for all three variables, and also for total motile count (TMC) in the
      prepared sperm. Calculating pregnancy losses per positive pregnancy showed a
      strong correlation with increasing female age. This was highly significant for
      biochemical losses but not for fetal heart miscarriages. Male age had no effect
      on rate of pregnancy loss. In conclusion, female age, FSH, AMH and TMC are good
      predictive factors for live-birth and therefore relate to essential in vivo steps
      in the reproductive process. 

PMID- 24127959
TI  - Clinical outcome, fertility and uterine artery Doppler scans in women with
      obstetric bilateral internal iliac artery ligation or embolisation.
AB  - The objective of our study was to report on the clinical outcome, fertility and
      uterine artery Doppler scans in patients with major postpartum haemorrhage,
      treated with bilateral internal iliac artery ligation or embolisation. We
      performed an observational analysis of successful bilateral internal iliac artery
      ligation or embolisation for postpartum haemorrhage in a tertiary hospital
      between 2001 and 2006. Clinical data and other medical/ surgical manoeuvres were
      recorded. Fertility data, menstrual cycle characteristics and uterine artery
      Doppler scans were assessed. Our success rate in bleeding control was 81%. Three
      patients got pregnant again 13, 16 and 23 months after the procedure. The one
      patient whose uterine artery was not identified in the Doppler scan was the only
      one who presented with secondary infertility. Three patients presented with
      secondary dysmenorrhoea. We concluded that internal iliac artery occlusion is an
      effective fertility-sparing procedure for postpartum haemorrhage. The absence of
      uterine revascularization could be a negative factor in future reproduction. Due
      to our limited sample size, larger studies are required to confirm these
      findings. 

PMID- 24127960
TI  - User's acceptability of OvuSense: a novel vaginal temperature sensor for
      prediction of the fertile period.
AB  - Measuring changes in core body temperature provides a valid method to detect
      ovulation and increase fertility. 'OvuSense' is a novel vaginal sensor that can
      predict the fertility window by recording and analysing the changes in
      intravaginal temperature records. This study aimed to determine patients
      'acceptability and satisfaction after using OvuSense'. We approached 13 women to
      complete a patient satisfaction survey after using OvuSense in a prospective,
      longitudinal, comparative study, to test its validity and accuracy in detecting
      ovulation over a minimum period of three cycles. All 13 women agreed to
      participate in this survey. The majority of the participants found the usage of
      the reader to be very easy; 76.9% of the women said it was extremely comfortable
      to use the device during the night and 76.9% found the idea of using the
      intravaginal reader to be very convenient. Overall, 69.2% of women were extremely
      satisfied using the device. The idea of detecting intravaginal core body
      temperature changes appears to be highly acceptable by women. 

PMID- 24127961
TI  - Effect of depression and anxiety on the success of pelvic floor muscle training
      for pelvic floor dysfunction.
AB  - The objective of this study was to determine the impact of the psychiatric
      symptoms of anxiety and depression, as assessed by validated questionnaires on
      the success of pelvic floor muscle training (PFMT). A prospective observational
      study was carried out by the Uro-gynaecological Physiotherapy Department at the
      Singleton Hospital, Swansea. A total of 108 consecutive women with pelvic floor
      dysfunction were referred for physiotherapy and admitted to the 6-month
      physiotherapy programme. They underwent subjective and objective assessments of
      their pelvic floor and psychological health at the beginning and end of the
      programme. A strong correlation was noted between the severity of anxiety and
      depression symptoms and the severity of their pelvic floor dysfunction. Following
      physiotherapy, apart from sexual function, all domains of pelvic floor
      dysfunction showed significant improvement. Based on the severity of their
      anxiety/depression symptoms, the patients were stratified into three groups. The
      group of patients that benefitted most had either no or only mild
      anxiety/depression. This study raises the question of whether a targeted approach
      should be undertaken for managing patients who, in addition to their pelvic floor
      dysfunction, demonstrate psychiatric symptoms. 

PMID- 24127962
TI  - Endovaginal ultrasound-assisted pain mapping in endometriosis and chronic pelvic
      pain.
AB  - The objective of this study was to determine if the combination of tenderness
      guided endovaginal ultrasound and digital pelvic exam (i.e. EVUS-assisted exam)
      for preoperative pain mapping, in cases without nodules or endometriomas,
      increases sensitivity/specificity for laparoscopic findings. This was a
      retrospective review of women with chronic pelvic pain +/- infertility with
      preoperative pain mapping exam prior to laparoscopy (n = 97, 2006-7). Predictor
      variables (EVUS-assisted exam vs digital pelvic exam alone, for pain mapping)
      were coded as tender vs non-tender. Primary outcome was findings on laparoscopy
      (e.g. endometriosis or adhesions) and was coded as abnormal vs normal. We found
      that EVUS-assisted exam had greater sensitivity (0.81, 95% CI: 0.70-0.89) for
      abnormal laparoscopy compared with digital pelvic exam alone (0.58, 95% CI: 0.46
      0.69) (McNemar's test, p < 0.001). Specificity was limited for both types of pain
      mapping (0.22, 95% CI: 0.08-0.44 for EVUS-assisted; and 0.39, 95% CI: 0.20-0.61
      for digital), with no significant difference (p = 0.13). In conclusion, in the
      absence of nodules or endometriomas, EVUS-assisted exam increases sensitivity,
      but with no benefit in specificity, for prediction of abnormal laparoscopy. 

PMID- 24127963
TI  - Laparoscopic vs robotic-assisted surgery for endometrial carcinoma in a centre
      with long laparoscopic experience.
AB  - Surgical outcomes and costs of laparoscopic and robotic hysterectomy for the
      treatment of endometrial carcinoma were compared in a centre with lengthy
      experience with laparoscopic surgery. The robotic cohort (n = 67) had a longer
      operative time than the laparoscopic cohort (n = 150) (p < 0.0001). Lymph node
      yields were similar for both surgical modalities, but the median of estimated
      blood loss was lower in the robotic group (50 ml vs 100 ml; p < 0.0001). The
      proportion of patients with hospital stay > 2 days and rate of overall
      complications were similar in both groups. Operative costs were (Euros) ?1,680
      and ?3,860 for the laparoscopic and robotic procedure, respectively. We conclude
      that robotic technology is feasible but does not provide short-term benefits for
      the treatment of endometrial carcinoma in a centre where laparoscopy has been
      established as the standardised minimally invasive surgical method. 

PMID- 24127964
TI  - Apoptosis through regulation of Bcl-2, Bax and Mcl-1 expressions in endometriotic
      cyst lesions and the endometrium of women with moderate to severe endometriosis.
AB  - The aim of the study was to evaluate apoptosis through regulation of Bcl-2, Bax
      and Mcl-1 proteins by comparing their expressions in endometriotic cyst lesions
      and the endometrium of the patients with moderate to severe endometriosis. This
      is a cross-sectional study of 30 women in reproductive age with a clinical or
      sonographic suspicion of endometrioma, who underwent laparoscopy. Bcl-2
      expression was positive both in cystic endometriotic lesions and endometrium, and
      its expression was significantly reduced in the cystic endometriotic lesions (p <
      0.0001). There was a significant difference in Bcl-2 expression between cystic
      endometriotic stromal cells and endometrial stromal cells (p < 0.0001). Bax
      expression was positive both in cystic endometriotic lesions and endometrium, and
      its expression was significantly lower in the endometrium (p < 0.0001). There was
      a significant difference in Bax expression between cystic endometriotic stromal
      cells and endometrial stromal cells (p = 0.03). Mcl-1 expression was positive
      both in cystic endometriotic lesions and endometrium, and its expression was
      significantly lower in the cystic endometriotic lesions (p = 0.003). Apoptosis
      may play a role in the pathophysiology of endometriosis by potentially
      contributing to the survival of regurgitating endometrial cells in the peritoneal
      cavity. 

PMID- 24127965
TI  - The role of cytology and other prognostic factors in endometrial cancer.
AB  - The clinical and prognostic value of positive cytology in women with endometrial
      cancer remains uncertain. The aim of our retrospective observational study was to
      determine whether in women with disease confined to the uterus, positive
      peritoneal cytology adversely affects disease-free (DFS) or overall survival
      (OS); to assess whether positive or negative cytology affects survival in women
      irrespective of stage and to assess whether the use of hysteroscopy or Pipelle
      for diagnosis affected cytology positivity rates. We have shown that median DFS
      and OS were almost identical for tumours confined to the uterus with and without
      positive peritoneal cytology. Women with tumours extending to the serosa or
      adnexa had a non-statistically significant shorter survival in comparison with
      women with stage I disease and negative cytology. Out of 59 women that had their
      cancer diagnosis based on a Pipelle biopsy of the endometrium, five had positive
      peritoneal washings. A total of 150 women had pre-treatment hysteroscopy; seven
      of these had positive peritoneal washings. There was no significant difference in
      the rates of positive cytology between these groups (4.6% vs 8.4%). In our cohort
      of un-staged women, positive peritoneal cytology did not adversely affect
      prognosis when disease was confined to the uterus. 

PMID- 24127966
TI  - Spontaneous coronary artery dissection in pregnancy.

PMID- 24127967
TI  - Pregnancy in a patient with a bioprosthetic tricuspid valve.

PMID- 24127968
TI  - Successful twin pregnancy in a 46,XY pure gonadal dysgenesis.

PMID- 24127969
TI  - Budd-Chiari syndrome during puerperium requiring liver transplantation.

PMID- 24127970
TI  - Vaginal delivery after augmentation cystoplasty and Mitrofanoff's procedure for
      incontinence following traumatic bladder neck transection.

PMID- 24127971
TI  - Splenic rupture: first case of successful conservation after caesarean delivery
      and anticoagulation.

PMID- 24127972
TI  - Right upper quadrant pain? Think outside the liver: a case of diaphragmatic
      perihepatic endometriosis.

PMID- 24127973
TI  - Abdominal compartment syndrome: a rare complication of an ovarian tumour.

PMID- 24127974
TI  - Acute presentation of clitoral phimosis in a 16-year-old girl.

PMID- 24127975
TI  - Advanced carcinoma of the cervix in a 17-year-old girl.

PMID- 24127976
TI  - Incidental finding of recurrent adenocarcinoma of the cervix during simple
      hysterectomy for menorrhagia.

PMID- 24127977
TI  - Ovarian hyperstimulation syndrome as a differential diagnosis to molar pregnancy.

PMID- 24127978
TI  - Re: Al-Sawaf A, El-Mazny A, Shohayeb A. 2013. A randomised controlled trial of
      sublingual misoprostol and intramuscular oxytocin for prevention of postpartum
      haemorrhage. Journal of Obstetrics and Gynaecology 33:277-279.

PMID- 24127983
TI  - Does periosteal scraping of the third metacarpal bone reduce the incidence of
      'bucked shins' in young Thoroughbred racehorses?
AB  - REASONS FOR PERFORMING STUDY: The occurrence of bucked shins in young
      Thoroughbred racehorses in North America is high. Although an altered training
      regime has demonstrated a significant decrease in this condition, trainers can be
      opposed to altering something as fundamental as their training routine.
      Periosteal scraping of the third metacarpal bone (McIII) is a putative
      prophylactic technique used to prevent bucked shins; therefore, a study to
      investigate the validity of the procedure is warranted. OBJECTIVES: To
      investigate whether prophylactic McIII scraping: 1) reduces the incidence of
      bucked shins in juvenile Thoroughbred horses at race speeds (breeze); and 2)
      allows increased cumulative breeze miles before the onset of disease. STUDY
      DESIGN: Nonrandomised prospective clinical study. METHODS: One hundred and
      seventy yearling Thoroughbreds from one farm, under one trainer, were enrolled in
      this study over one training season; 85 horses were treated and 85 horses were
      control animals. Horses were observed for bucked shins over 5 cumulative breeze
      miles. The objectives were evaluated by comparing incidence rates and Kaplan
      Meier plots. RESULTS: The incidence rate for bucked shins was 0.059 cases per
      breezed mile in the treatment group, compared with 0.103 cases per breezed mile
      in the control group. Comparison of Kaplan-Meier plots of breeze miles for the 2
      groups demonstrated a significant difference between groups (P = 0.035). Horses
      that developed bucked shins following periosteal shin scraping breezed an average
      of 3.52 miles before the onset of disease, compared to 2.50 miles for horses not
      prophylactically treated (P = 0.005). CONCLUSIONS: Periosteal McIII scraping
      reduced the incidence rate of bucked shins. The procedure allowed treated horses
      to breeze greater cumulative distances before an incident but failed to prevent
      the disease over the long term. Further investigation into this commonly used
      prophylactic technique is required.

PMID- 24127985
TI  - Prevalence and correlates of childhood sexual abuse in adults consulting for
      sexual problems.
AB  - The main objectives of the study were to assess the prevalence of childhood
      sexual abuse in individuals consulting for sexual therapy and to explore the
      association between a history of childhood sexual abuse and psychological and
      couple functioning. A sample of 218 adults receiving sex therapy completed
      questionnaires assessing depressive and anxious symptomatology, as well as dyadic
      adjustment. Prevalence of childhood sexual abuse was high in women (56%) and men
      (37%), and clients with a history of childhood sexual abuse were more likely to
      report psychological and relationship problems. Findings should aware clinicians
      of the need to assess sexual trauma and related outcomes. 

PMID- 24127984
TI  - Bortezomib enhances fatty liver preservation in Institut George Lopez-1 solution
      through adenosine monophosphate activated protein kinase and Akt/mTOR pathways.
AB  - OBJECTIVES: The aim of this study is to investigate the protective mechanisms
      induced by bortezomib added to Institut George Lopez (IGL)-1 preservation
      solution to protect steatotic livers against cold ischaemia reperfusion injury
      and to examine whether these mechanisms occur through the activation of adenosine
      monophosphate activated protein kinase (AMPK), Akt/mTOR pathways. METHODS:
      Steatotic livers from obese rats were preserved for 24 h (at 4  degrees C) in IGL
      1 solution with or without bortezomib (100 nM) or pretreated with AMPK inhibitor
      adenine 9-alpha-D-arabinofuranoside and preserved in IGL-1 + bortezomib. Livers
      were then perfused for 2 h at 37  degrees C. Liver injury (alanine
      aminotransferase/aspartate aminotransferase) and function (bile production and
      vascular resistance) were measured. Also, Akt/mTOR, phosphorylated AMPK (pAMPK)
      and apoptosis were determined by Western blot analyses. KEY FINDINGS: Bortezomib
      addition to IGL-1 solution significantly reduced steatotic liver injury, improved
      graft function and decreased liver apoptosis. These benefits were diminished by
      the pretreatment of obese rats with AMPK inhibitor Ara. Western blot analyses
      showed a significant increase in pAMPK after ischaemia and reperfusion. We also
      observed a significant phosphorylation of Akt in IGL-1 +bortezomib group that, in
      turn, induced the phosphorylation of mTOR and glycogen synthase kinase 3beta.
      CONCLUSIONS: Bortezomib, at low and non toxic concentration, is a promising
      additive to IGL-1 solution for steatotic liver preservation. Its protective
      effect is due to the activation of AMPK and Akt/mTOR pathways.

PMID- 24127986
TI  - Type I error and statistical power of the Mantel-Haenszel procedure for detecting
      DIF: a meta-analysis.
AB  - This article presents a meta-analysis of studies investigating the effectiveness
      of the Mantel-Haenszel (MH) procedure when used to detect differential item
      functioning (DIF). Studies were located electronically in the main databases,
      representing the codification of 3,774 different simulation conditions, 1,865
      related to Type I error and 1,909 to statistical power. The homogeneity of effect
      size distributions was assessed by the Q statistic. The extremely high
      heterogeneity in both error rates (I2 = 94.70) and power (I2 = 99.29), due to the
      fact that numerous studies test the procedure in extreme conditions, means that
      the main interest of the results lies in explaining the variability in detection
      rates. One-way analysis of variance was used to determine the effects of each
      variable on detection rates, showing that the MH test was more effective when
      purification procedures were used, when the data fitted the Rasch model, when
      test contamination was below 20%, and with sample sizes above 500. The results
      imply a series of recommendations for practitioners who wish to study DIF with
      the MH test. A limitation, one inherent to all meta-analyses, is that not all the
      possible moderator variables, or the levels of variables, have been explored.
      This serves to remind us of certain gaps in the scientific literature (i.e.,
      regarding the direction of DIF or variances in ability distribution) and is an
      aspect that methodologists should consider in future simulation studies.

PMID- 24127987
TI  - Switching principal component analysis for modeling means and covariance changes
      over time.
AB  - Many psychological theories predict that cognitions, affect, action tendencies,
      and other variables change across time in mean level as well as in covariance
      structure. Often such changes are rather abrupt, because they are caused by
      sudden events. To capture such changes, one may repeatedly measure the variables
      under study for a single individual and examine whether the resulting
      multivariate time series contains a number of phases with different means and
      covariance structures. The latter task is challenging, however. First, in many
      cases, it is unknown how many phases there are and when new phases start. Second,
      often a rather large number of variables is involved, complicating the
      interpretation of the covariance pattern within each phase. To take up this
      challenge, we present switching principal component analysis (PCA). Switching PCA
      detects phases of consecutive observations or time points (in single subject
      data) with similar means and/or covariation structures, and performs a PCA per
      phase to yield insight into its covariance structure. An algorithm for fitting
      switching PCA solutions as well as a model selection procedure are presented and
      evaluated in a simulation study. Finally, we analyze empirical data on
      cardiorespiratory recordings.

PMID- 24127988
TI  - Cognitive diagnostic assessment via Bayesian evaluation of informative diagnostic
      hypotheses.
AB  - There exist diverse approaches that can be used for cognitive diagnostic
      assessment, such as mastery testing, constrained latent class analysis, rule
      space methodology, diagnostic cognitive modeling, and person-fit analysis. Each
      of these approaches can be used within 1 of the 4 psychometric perspectives on
      diagnostic testing discussed by Borsboom (2008), that is, the dimensional,
      diagnostic, constructivist, and causal system perspectives. Bayesian evaluation
      of informative diagnostic hypotheses is an alternative for each of the other
      approaches that is more flexible in the diagnostic hypotheses that can be
      evaluated, and it can be used in each of the 4 psychometric perspectives on
      diagnostic testing. After being formulated, informative diagnostic hypotheses are
      evaluated by means of the Bayes factor using only the data from the person to be
      diagnosed. Already, relatively small diagnostic tests render Bayes factors that
      provide convincing evidence in favor of 1 of the diagnostic hypotheses under
      consideration.

PMID- 24127989
TI  - Nanostructuring thin polymer films with optical near fields.
AB  - In the present work, we report on the application of optical near fields to
      nanostructuring of poly(trimethylene terephthalate) (PTT) thin films. By exposure
      to a single ultraviolet nanosecond laser pulse, the spatial intensity modulation
      of the near-field distribution created by a silica microsphere is imprinted into
      the films. Setting different angles of incidence of the laser, elliptical or
      circular periodic ring patterns can be produced with periods as small as half the
      laser wavelength used. These highly complex patterns show optical and
      topographical contrast and can be characterized by optical microscopy (OM) and
      atomic force microscopy (AFM). We demonstrate the key role of the laser
      wavelength and coherence length in achieving smooth, extended patterns in PTT by
      using excimer laser (193 nm) and Nd:YAG laser (266 nm) pulses. Reference
      experiments performed in Ge2Sb2Te5 (GST) demonstrate that nanopatterning in PTT
      is triggered by ablation as opposed to GST, in which nanopatterning originates
      from laser-induced phase change, accompanied by a small topographical contrast.
      The experiments presented in this work demonstrate the suitability of optical
      near fields for structuring polymer films, opening up new possibilities for
      nanopatterning and paving the way for potential applications where optical near
      fields and polymer nanostructures are involved. 

PMID- 24127990
TI  - Effect of a non-forage fiber of red bean hulls on ruminal mat characteristics,
      chewing activity and milk production in dairy cows.
AB  - The evaluation of red bean hulls (RBH) as a non-forage fiber source on ruminal
      mat formation, chewing activity and milk production was determined using two
      experiments. In experiment 1, four non-lactating, rumen-cannulated Holstein cows
      were offered a control diet of 60.1% forage, and an RBH diet of 51.6% forage and
      9.4% RBH. Although the neutral detergent fiber (NDF) intake was higher with the
      RBH diet than the control diet, the physically effective NDF (peNDF) intake was
      lower. The rumination period tended to be longer with the RBH diet than with the
      control diet and the ruminal mat was formed even when the RBH diet was consumed.
      Ruminal fermentation parameters were not affected by treatment. In experiment 2,
      40 lactating cows were fed a control diet of 53.4% forage or an RBH diet of 50.3%
      forage and 8.1% RBH. Dry matter intake, chewing activity and milk production were
      not affected by diet. Cows sorted against NDF in the control diet, but not in the
      RBH diet. It is concluded that normal ruminal function can be maintained because
      the ruminal mat was stratified and rumination activity was not reduced even when
      a low peNDF diet that contained RBH was given to dairy cows. 

PMID- 24127991
TI  - Potential enhanced ability of giant squid to detect sperm whales is an exaptation
      tied to their large body size.
AB  - It has been hypothesized that sperm whale predation is the driver of eye size
      evolution in giant squid. Given that the eyes of giant squid have the size
      expected for a squid this big, it is likely that any enhanced ability of giant
      squid to detect whales is an exaptation tied to their body size. Future studies
      should target the mechanism behind the evolution of large body size, not eye
      size. Reconstructions of the evolutionary history of selective regime, eye size,
      optical performance, and body size will improve the understanding of the
      evolution of large eyes in large ocean animals. 

PMID- 24127992
TI  - Combination of an intrauterine balloon and the "holding the cervix" technique for
      hemostasis of postpartum hemorrhage and for prophylaxis of acute recurrent
      uterine inversion.

PMID- 24127993
TI  - Management of avulsions in Switzerland 2007-2010.
AB  - INTRODUCTION: More than 50% of all European children suffer a dental injury (DI),
      for which the emergency treatment is usually carried out by a general dentist.
      The aim of this survey was to assess the management of avulsions in Switzerland
      as the common treatment procedures used by Swiss dentists in such cases. As yet
      there are no published data on the treatment of DI in Switzerland. MATERIALS AND
      METHODS: A 15-item questionnaire was distributed to all members of the Swiss
      Dental Society containing questions about the dentists' profile, the distribution
      of dental injuries they had encountered affecting permanent teeth, especially
      avulsions, the number of treated avulsions and questions about how the dentists
      had treated an avulsion in the past 3 years. RESULTS: The response rate was 41%
      (n = 1350). On average, two avulsions per practitioner had been seen in the past
      3 years. The dental practitioners who encountered cases of tooth avulsion treated
      an average of 2.8 avulsions in that time frame. Most dentists applied
      conventional intraoral root canal treatment, which was performed on average 9
      days after replantation. As the intracanal dressing, calcium hydroxide was used
      by 69.8% and Ledermix(r) by 49.3%, while Asphaline(r) was used by only 1.8%
      (multiple answers were possible). Seventy-eight percent (78.1%) of the
      respondents had received postgraduate dental trauma education. Dentists with such
      an education used Ledermix(r) significantly more often (P = 0.002), and the time
      until pulp extirpation was significantly shorter (P < 0.001). The favorite splint
      after replantation was the Titanium Trauma Splint(r), followed by the wire
      composite splint and the bracket splint, while the aligner was used very rarely.
      The average splinting time was 11.2 days. Eighty-one percent (81.1%) of the
      respondents had a tooth rescue box in their office, 41.1% had Emdogain(r), 25.9%
      had tetracycline for local application, and 14.7% had steroids for local
      application available. CONCLUSION: Although only a few patients with avulsions
      had presented in Swiss dental offices in the past 3 years, their treatment was
      closely aligned to current guidelines.

PMID- 24127994
TI  - Vinylnitrene formation from 3,5-diphenyl-isoxazole and 3-benzoyl-2-phenylazirine.
AB  - Photolysis of 1 in argon-saturated acetonitrile yields 2, whereas in oxygen
      saturated acetonitrile small amounts of benzoic acid and benzamide are formed in
      addition to 2. Similarly, photolysis of 2 in argon-saturated acetonitrile results
      in 1 and a trace amount of 3, whereas in oxygen-saturated acetonitrile the major
      product is 1 in addition to the formation of small amounts of benzoic acid and
      benzamide. Laser flash photolysis of 1 results in an absorption due to triplet
      vinylnitrene 4 (broad absorption with lambda(max) at 360 nm, tau = 1.8 MUs,
      acetonitrile) that is formed with a rate constant of 1.2 * 10(7) s(-1) and decays
      with a rate constant of 5.6 * 10(5) s(-1). Laser flash photolysis of 2 in argon
      saturated acetonitrile likewise results in the formation of triplet vinylnitrene
      4 but also ylide 5 (lambda(max) at 440 nm, tau = 13 MUs). The rate constant for
      forming 4 in argon-saturated acetonitrile is 1.6 * 10(7) s(-1). In oxygen
      saturated acetonitrile, vinylnitrene 4 reacts to form the peroxide radical 6
      (lambda(max) 360 nm, ~0.7 MUs, acetonitrile) at a rate of 2 * 10(9) M(-1) s(-1).
      Density functional theory calculations were performed to aid in the
      characterization of vinylnitrene 4 and peroxide 6 and to support the proposed
      mechanism for the formation of these intermediates.

PMID- 24127995
TI  - Clinical, radiological, histological and molecular characteristics of paediatric
      epithelioid glioblastoma.
AB  - AIMS: A few case series in adults have described the characteristics of
      epithelioid glioblastoma (e-GB), one of the rarest variants of this cancer. We
      evaluated clinical, radiological, histological and molecular characteristics in
      the largest series to date of paediatric e-GB. METHODS: Review of clinical
      characteristics and therapy, imaging studies and histology was performed in
      patients younger than 22 years with e-GB seen at our institution over 15 years.
      Sequencing of hotspot mutations and fluorescence in situ hybridization of
      relevant genes were undertaken. RESULTS: Median age at diagnosis of six patients
      was 7.6 years. Tumours originated in the cerebral cortex (n = 2) or diencephalon
      (n = 4). Three patients presented with acute, massive haemorrhage and three had
      leptomeningeal dissemination at diagnosis. Paediatric e-GB had the typical
      histological characteristics seen in adult tumours. Universal immunoreactivity
      for INI1 and lack of diverse protein expression were seen in all cases. One
      tumour had a chromosome 22q loss. Three tumours (50%) harboured a BRAF: p.V600E.
      One thalamic tumour had an H3F3A p.K27M. All patients received radiation therapy
      with (n = 3) or without chemotherapy (n = 3). All patients experienced tumour
      progression with a median survival of 169 days. One patient with nonmetastatic
      disease had early leptomeningeal progression. Two patients had symptomatic tumour
      spread outside the central nervous system (CNS) through a ventriculoperitoneal
      shunt. One additional patient had widespread metastases outside the CNS
      identified at autopsy. CONCLUSIONS: Paediatric e-GBs are rare cancers with an
      aggressive behaviour that share histological and genetic characteristics with
      their adult counterparts. BRAF inhibition is a potential treatment for these
      tumours.

PMID- 24127996
TI  - Chronic productive cough is associated with death in smokers with early COPD.
AB  - Cough and phlegm are common in COPD. Previous studies have shown conflicting
      evidence regarding their association with mortality and lung function. We sought
      to better understand how cough and phlegm impact mortality and lung function in
      COPD. We analyzed data from the Lung Health Study, consisting of 5,887 smokers
      with mild to moderate airflow obstruction followed longitudinally. We assessed
      the association between baseline symptoms of cough alone, phlegm alone, and cough
      and phlegm with 12.5-year mortality and annual lung function decline. Average age
      at entry was 48.5 years (+/- 6.8) with 63% males and 4% African Americans. Cough
      alone was present in 17%, phlegm alone in 12%, while 31% had both. Neither
      symptom alone was associated with death, but the combination was associated with
      increased risk of death after adjustment for age, gender, race, smoking status at
      year 5, pack-years smoked, randomization group, baseline FEV1 percent predicted
      (HR 1.27, 95% CI 1.02-1.59). Individuals with cough and phlegm together more
      commonly died of respiratory causes than those without. Cough with phlegm was
      associated with 48 mL lower baseline FEV1 (95% CI -90, -6), while neither symptom
      alone was associated with baseline FEV1. No symptom was associated with FEV1
      longitudinally. Cough and phlegm together are associated with mortality and lung
      function decrement in mild-to-moderate COPD, independent of lung function and
      smoking status. Respiratory causes of death are common among those with cough and
      phlegm. Such information can help to identify subsets of individuals with COPD
      having higher risk for adverse outcomes.

PMID- 24127997
TI  - Nanoemulsions and nonwoven fabrics carrying AgNPs: antibacterial but may be
      cytotoxic.
AB  - Abstract The aim of this study is to prepare nonwoven fabrics carrying silver
      nanoparticles (AgNPs), and to investigate their antibacterial activities and
      cytotoxicities in parallel. AgNPs were impregnated from their nanoemulsions onto
      two commercially available nonwoven fabrics: pure-cotton fabrics (PCF) and
      polyester/viscous fabrics (PVF), by a simple adsorption (dipping) and were then
      heat stabilized. PCF exhibited stronger antibacterial effects on both
      Staphylococcus aureus and Escherichia coli. In-vitro cell culture studies
      demonstrated that AgNPs nanoemulsions and also fabrics carrying them were
      cytotoxic on L929-fibroblasts in all concentrations used here (6.25-400 ppm) in
      different extends. Only the fabrics loaded with AgNPs using nanoemulsion with the
      lowest concentration of 6.25 ppm exhibited low cytotoxicity but were still
      antibacterial. 

PMID- 24127998
TI  - Redox homeostasis is compromised in vivo by the metabolites accumulating in 3
      hydroxy-3-methylglutaryl-CoA lyase deficiency in rat cerebral cortex and liver.
AB  - 3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a disorder biochemically
      characterized by the predominant accumulation of 3-hydroxy-3-methylglutarate
      (HMG), 3-methylglutarate (MGA), 3-methylglutaconate and 3-hydroxyisovalerate in
      tissues and biological fluids of the affected patients. Neurological symptoms and
      hepatopathy are commonly found in HL deficiency, especially during metabolic
      crises. Since the mechanisms of tissue damage in this disorder are not well
      understood, in the present study we evaluated the ex vivo effects of acute
      administration of HMG and MGA on important parameters of oxidative stress in
      cerebral cortex and liver from young rats. In vivo administration of HMG and MGA
      provoked an increase of carbonyl and carboxy-methyl-lysine formation in cerebral
      cortex, but not in liver, indicating that these metabolites induce protein
      oxidative damage in the brain. We also verified that HMG and MGA significantly
      decreased glutathione concentrations in both cerebral cortex and liver, implying
      a reduction of antioxidant defenses. Furthermore, HMG and MGA increased 2',7'
      dichlorofluorescin oxidation, but did not alter nitrate and nitrite content in
      cerebral cortex and liver, indicating that HMG and MGA effects are mainly
      mediated by reactive oxygen species. HMG and MGA also increased the activities of
      superoxide dismutase and catalase in cerebral cortex and liver, whereas MGA
      decreased glutathione peroxidase activity in cerebral cortex. Our present data
      showing a disruption of redox homeostasis in cerebral cortex and liver caused by
      in vivo administration of HMG and MGA suggest that this pathomechanism may
      possibly contribute to the brain and liver abnormalities observed in HL-deficient
      patients.

PMID- 24127999
TI  - Role of premixed insulin analogues in the treatment of patients with type 2
      diabetes mellitus: a narrative review.
AB  - Because of the progressive nature of type 2 diabetes mellitus (T2DM), insulin
      therapy will eventually become necessary in most patients. Recent evidence
      suggests that maintaining optimal glycemic control by early insulin therapy can
      reduce the risk of microvascular and macrovascular complications in patients with
      T2DM. The present review focuses on relevant clinical evidence supporting the use
      of premixed insulin analogues in T2DM when intensifying therapy, and as starter
      insulins in insulin-naive patients. Our aim is to provide relevant facts and
      clinical evidence useful in the decision-making process of treatment selection
      and individualized treatment goal setting to obtain sustained blood glucose
      control. 

PMID- 24128000
TI  - Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of
      nitroimidazole-sulfonamides/sulfamides/sulfamates.
AB  - A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate
      moieties were designed and synthesized as radio/chemosensitizing agent targeting
      the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new
      compounds were nanomolar inhibitors of these isoforms. Crystallographic studies
      on the complex of hCA II with the lead sulfamide derivative of this series
      clarified the binding mode of this type of inhibitors in the enzyme active site
      cavity. Some of the best nitroimidazole CA IX inhibitors showed significant
      activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and
      HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in
      cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX
      containing tumors. Such CA inhibitors, specifically targeting the tumor
      associated isoforms, are candidates for novel treatment strategies against
      hypoxic tumors overexpressing extracellular CA isozymes. 

PMID- 24128001
TI  - Intravenous immunoglobulin modulates the expansion and cytotoxicity of CD8+ T
      cells.
AB  - Intravenous immunoglobulin (IVIg) is successfully used in the treatment of
      autoimmune diseases involving self-reactive CD8(+) T cells. However, its direct
      influence on the cytotoxic response remains unknown. Using an antigen cross
      presentation assay and a mouse model of ovalbumin (OVA) immunization, we showed
      that IVIg decreases the in vitro activation, proliferation and cytokine secretion
      of OVA-specific CD8(+) T cells (OT-I), as well as the in vivo generation of OVA
      specific CD8(+) T cells. In addition, IVIg significantly decreases the proportion
      of perforin- and CD107a-expressing CD8(+) T cells, and inhibits the cytotoxic
      activity of OVA-activated OT-I cells. The interference of IVIg with the CD8(+) T
      cell response is associated with T-cell receptor blockade, therefore reducing the
      interaction between effector and target cells. A similar blockade is observed on
      human CD8(+) T cells, suggesting that the observations reported here could apply
      to the IVIg-mediated improvement of CD8(+) T-cell-mediated autoimmune conditions
      in human patients. 

PMID- 24128002
TI  - Continuing to care.

PMID- 24128003
TI  - Removal of ruthenium using a silica gel supported reagent.
AB  - A solid-supported isocyanide ligand was developed to destroy active metathesis
      catalysts and to remove ruthenium byproducts from metathesis reactions. This
      method was able to significantly reduce the concentration of residual ruthenium
      from the organic products of several alkene and ene-yne metathesis reactions,
      under a variety of different conditions. 

PMID- 24128005
TI  - When the body is past fixing: caring for bodies, caring for people.
AB  - AIMS AND OBJECTIVES: To discuss the social context within which end-of-life
      nursing care takes place and to consider palliative options of last resort and
      the differences between societal and professional views on these. BACKGROUND: The
      distinction between life and death is not so straightforward as was once the
      case. Resuscitation and the increasing capability of intensive care to 'save'
      patients have implications for nursing practice in a society where there is an
      increasing demand that individuals should be able to choose the time of their
      death. METHODS: This is a discursive paper. CONCLUSIONS: There are differences
      between the professional view on end-of-life options and the societal debates
      calling for a more libertarian approach. The problem for professionals is that
      the call for choice of the individual involves a different approach to end-of
      life care, an approach that does not sit well with current professional ethics.
      One way forward might be a gradual reconsidering of what end-of-life care might
      reasonably encompass. RELEVANCE TO CLINICAL PRACTICE: Nurses are the healthcare
      workers who have the most prolonged and intimate contact with bodies. The way in
      which we conceptualise the body is central to much of the work carried out in the
      transition between life and death and is an important part of nursing.

PMID- 24128004
TI  - WTP for a QALY and health states: More money for severer health states?
AB  - BACKGROUND: In economic evaluation, cost per quality-adjusted life year (QALY) is
      generally used as an indicator for cost-effectiveness. Although JPY 5 million to
      6 million (USD 60, 000 to 75,000) per QALY is frequently referred to as a
      threshold in Japan, do all QALYs have the same monetary value? METHODS: To
      examine the relationship between severity of health status and monetary value of
      a QALY, we obtained willingness to pay (WTP) values for one additional QALY in
      eight patterns of health states. We randomly sampled approximately 2,400
      respondents from an online panel. To avoid misunderstanding, we randomly
      allocated respondents to one of 16 questionnaires, with 250 responses expected
      for each pattern. After respondents were asked whether they wanted to purchase
      the treatment, double-bounded dichotomous choice method was used to obtain WTP
      values. RESULTS: The results clearly show that the WTP per QALY is higher for
      worse health states than for better health states. The slope was about JPY -1
      million per 0.1 utility score increase. The mean and median WTP values per QALY
      for 16 health states were JPY 5 million, consistent with our previous survey. For
      respondents who wanted to purchase the treatment, WTP values were significantly
      correlated with household income. CONCLUSION: This survey shows that QALY based
      on the EQ-5D does not necessarily have the same monetary value. The WTP per QALY
      should range from JPY 2 million (USD 20,000) to JPY 8 million (USD 80,000),
      corresponding to the severity of health states.

PMID- 24128006
TI  - Absence of gender-based differences in outcome of patients with hospital-acquired
      pneumonia.
AB  - BACKGROUND: The objective of this analysis was to evaluate the association
      between gender and clinical outcomes in intensive care unit (ICU) patients with
      hospital-acquired pneumonia (HAP) since data thus far are controversial. METHODS:
      Data from a convenience sample of ICU patients with HAP, including ventilator
      associated and health care-associated pneumonia, were retrospectively collected
      from four academic institutions (Improving Medicine through Pathway Assessment of
      Critical Therapy in Hospital-Acquired Pneumonia [IMPACT-HAP] study). Outcomes
      included 28-day mortality, clinical failure at day 14, hospital and ICU length of
      stay (LOS), and duration of mechanical ventilation. We compared baseline
      characteristics and performed multivariate analysis to identify factors
      independently associated with mortality. RESULTS: Among 416 patients, 271 were
      men and 145 were women. Women were older (62.4+/-16.9 vs. 55.7+/-16.5 years,
      p<0.001) and more critically ill, with Acute Physiology and Chronic Health
      Evaluation (APACHE) II scores of 21 vs. 19 (p=0.004). Day-28 mortality was 30%
      for women and 24% for men (p=0.25). Increased 28-day mortality was associated
      with severity of illness, age, ventilator-associated pneumonia, vascular disease,
      and hospital LOS prior to pneumonia diagnosis. No significant differences were
      found in the distribution of bacteria pathogens or in clinical failure rates (36%
      vs. 31%) between genders. Duration in days of mechanical ventilation, ICU LOS and
      hospital LOS after the diagnosis of pneumonia were not significantly different
      between men and women. Analyzing data for women based on presumed pre- or
      postmenopausal status (age breakpoint of 50 years), showed an increased in ICU
      LOS (15 vs. 25 days; p=0.0026) and hospital LOS (22 vs. 30 days; p=0.05) for
      women <=50 years. No differences were noted in 28-day mortality (24.3% vs. 13.1%;
      p=0.18) in women <=50 years of age. CONCLUSIONS: In ICU patients with pneumonia,
      female gender was not associated with worse outcomes or increased resource
      utilization compared to male gender. Further studies are needed to evaluate
      menopausal status and outcomes in women with pneumonia.

PMID- 24128007
TI  - Close relationships between polar auxin transport and graviresponse in plants.
AB  - Gravitational force on Earth is one of the major environmental factors affecting
      plant growth and development. Spacecraft and the International Space Station
      (ISS), and a three-dimensional (3-D) clinostat have been available to clarify the
      effects of gravistimulation on plant growth and development in space and on
      ground conditions, respectively. Under a stimulus-free environment such as space
      conditions, plants show a growth and developmental habit designated as
      'automorphosis' or 'automorphogenesis'. Recent studies in hormonal physiology,
      together with space and molecular biology, have demonstrated the close
      relationships between automorphosis and polar auxin transport. Reduced polar
      auxin transport in space conditions, or induced by the application of polar auxin
      transport inhibitors, substantially induced automorphosis or automorphosis-like
      growth and development, indicating that polar auxin transport is responsible for
      graviresponse in plants. This concise review covers graviresponse in plants and
      automorphosis observed in space conditions, and polar auxin transport related to
      graviresponse in etiolated Alaska and ageotropum pea seedlings. Molecular aspects
      of polar auxin transport clarified in recent studies are also described. 

PMID- 24128008
TI  - Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase
      (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.
AB  - Protein kinase C-related kinases (PRKs) are members of the protein kinase C
      superfamily of serine-threonine kinases and can be activated by binding to
      members of the Rho family of GTPases via a Rho-binding motif known as an HR1
      domain. Three tandem HR1 domains reside at the N-terminus of the PRKs. We have
      assessed the ability of the HR1a and HR1b domains from the three PRK isoforms
      (PRK1, PRK2, and PRK3) to interact with the three Rho isoforms (RhoA, RhoB, and
      RhoC). The affinities of RhoA and RhoC for a construct encompassing both PRK1 HR1
      domains were similar to those for the HR1a domain alone, suggesting that these
      interactions are mediated solely by the HR1a domain. The affinities of RhoB for
      both the PRK1 HR1a domain and the HR1ab didomain were higher than those of RhoA
      or RhoC. RhoB also bound more tightly to the didomain than to the HR1a domain
      alone, implicating the HR1b domain in the interaction. As compared with PRK1 HR1
      domains, PRK2 and PRK3 domains bind less well to all Rho isoforms. Uniquely,
      however, the PRK3 domains display a specificity for RhoB that requires both the C
      terminus of RhoB and the PRK3 HR1b domain. The thermal stability of the HR1a and
      HR1b domains was also investigated. The PRK2 HR1a domain was found to be the most
      thermally stable, while PRK2 HR1b, PRK3 HR1a, and PRK3 HR1b domains all exhibited
      lower melting temperatures, similar to that of the PRK1 HR1a domain. The lower
      thermal stability of the PRK2 and PRK3 HR1b domains may impart greater
      flexibility, driving their ability to interact with Rho isoforms. 

PMID- 24128009
TI  - Asthma among workers in healthcare settings: role of disinfection with quaternary
      ammonium compounds.
AB  - INTRODUCTION: An increased incidence of asthma has been reported among healthcare
      workers. The role of quaternary ammonium compounds (QACs), commonly used in
      cleaning/disinfection products, has not been clearly defined. The aim of this
      study was to analyse associations between asthma and occupational exposure to
      disinfectants, especially QACs. METHODS: The study was performed on a stratified
      random sample of the various healthcare departments of 7 healthcare settings. The
      study included: questionnaire, physical examination and specific IgE assays.
      Occupational exposure assessment was performed by means of a work questionnaire,
      workplace studies and a review of products ingredients. Data were analysed by
      logistic regression. RESULTS: Response rate was 77%; 543 workers (89% female)
      participated; 37.1% were registered nurses (RNs), 16.4% auxiliary nurses (ANs),
      17.3% cleaners; 32.8% were atopic. 335 participants were exposed to QACs. Nursing
      professionals reported a significantly higher risk of reported physician
      diagnosed asthma and, for RNs, of nasal symptoms at work than administrative
      staff working in healthcare sector. This risk was particularly marked during
      disinfection tasks and when exposure to QACs. Exposure to QACs increased
      significantly the risk of reported physician-diagnosed asthma and nasal symptoms
      at work (adjusted OR = 7.5 and 3.2, respectively). No significant association was
      found with other exposures such as latex glove use, chlorinated products/bleach
      or glutaraldehyde. CONCLUSION: RNs and ANs presented a higher risk of reported
      asthma than administrative staff. The highest risk was associated with tasks
      involving dilution of disinfection products by manual mixing, suggesting possible
      exposure to repeated peaks of concentrated products known to be strong
      respiratory irritants. Workplace interventions should be conducted to more
      clearly determine QAC exposure and improve disinfection procedures.

PMID- 24128010
TI  - Positive surgical margins: rate, contributing factors and impact on further
      treatment: findings from the Prostate Cancer Registry.
AB  - OBJECTIVE: To describe the characteristics of patients with and without positive
      surgical margins (PSMs) and to analyse the impact of PSMs on secondary cancer
      treatment after radical prostatectomy (RP), with short-term follow-up. PATIENTS
      AND METHODS: We analysed data from 2385 consecutive patients treated using RP,
      who were notified to the Prostate Cancer Registry by 37 hospitals in Victoria,
      Australia between August 2008 and February 2012. Independent and multivariate
      models were constructed to predict the likelihood of PSMs. Independent and
      multivariate predictors of secondary treatment after RP in the initial 12 months
      after diagnosis were also assessed. RESULTS: Data on PSM status were collected
      for 2219/2385 (93%) patients. In total 592/2175 (27.2%) RPs resulted in PSMs;
      102/534 (19.1%) in the low-risk group, 317/1218 (26.0%) in the intermediate-risk
      group, 153/387 (39.5%) in the high-risk group, and 9/11 (81.8%) in the very-high
      risk disease group of patients. Patients having surgery in a hospital where <10
      RPs occur each year were significantly more likely to have a PSM (incidence rate
      ratio [IRR] 1.44, 95% confidence interval [CI] 1.07-1.93) and those in the
      intermediate-, high- or very-high-risk groups (IRR 1.34, 95% CI 1.09-1.65, P =
      0.007, IRR 1.96, 95% CI 1.57-2.45, P < 0.001 and IRR 3.81, 95% CI 2.60-5.60, P <
      0.001, respectively) were significantly more likely to have a PSM than those in
      the low-risk group (IRR 2.50, 95% CI 1.23-5.11, P = 0.012). Patients with PSMs
      were significantly less likely to have been treated at a private hospital than a
      public hospital (IRR 0.76, 95% CI 0.63-0.93, P = 0.006) or to have undergone
      robot-assisted RP (IRR 0.69, 95% CI 0.55-0.87; P = 0.002) than open RP. Of the
      2182 patients who underwent RP in the initial 12 months after diagnosis, 1987
      (91.1%) received no subsequent treatment, 123 (5.6%) received radiotherapy, 47
      (2.1%) received androgen deprivation therapy (ADT) and 23 (1.1%) received a
      combination of radiotherapy and ADT. Two patients (0.1%) received chemotherapy
      combined with another treatment. At a multivariate level, predictors of
      additional treatment after RP in the initial 12 months included having a PSM
      compared with a negative surgical margin (odds ratio [OR] 5.61, 95% CI 3.82-8.22,
      P < 0.001); pT3 compared with pT2 disease (OR 4.72, 95% CI 2.69-8.23, P < 0.001);
      and having high- or very-high-risk disease compared with low-risk disease (OR
      4.36, 95% CI 2.24-8.50, P < 0.001 and OR 4.50, 95% CI 1.34-15.17, P = 0.015,
      respectively). Patient age, hospital location and hospital type were not
      associated with secondary treatment. Patients undergoing robot-assisted RP were
      significantly less likely to receive additional treatment than those receiving
      open RP (OR 0.59, 95% CI 0.39-0.88, P = 0.010). CONCLUSIONS: These data indicate
      an important association between hospital status and PSMs, with patients who
      underwent RP in private hospitals less likely than those in public hospitals to
      have a PSM. Patients treated in lower-volume hospitals were more likely to have a
      PSM and less likely to receive additional treatment after surgery in the initial
      12 months, and robot-assisted RP was associated with fewer PSMs than was open RP
      in this non-randomized observational study. PSM status and pathological T3
      disease are both important and independent predictors of secondary cancer
      treatment for patients undergoing RP. A robot-assisted RP approach appears to
      decrease the likelihood of subsequent treatment, when compared with the open
      approach.

PMID- 24128011
TI  - Strengthening alginate/polyacrylamide hydrogels using various multivalent
      cations.
AB  - We successfully synthesized a family of alginate/polyacrylamide hydrogels using
      various multivalent cations. These hydrogels exhibit exceptional mechanical
      properties. In particular, we discovered that the hydrogels cross-linked by
      trivalent cations are much stronger than those cross-linked by divalent cations.
      We demonstrate stretchability and toughness of the hydrogels by inflating a
      hydrogel sheet into a large balloon, and the elasticity by using a hydrogel block
      as a vibration isolator in a forced vibration test. The excellent mechanical
      properties of these hydrogels may open up applications for hydrogels. 

PMID- 24128012
TI  - Iodide-catalyzed synthesis of N-nitrosamines via C-N cleavage of nitromethane.
AB  - An iodide-catalyzed process to synthesize N-nitrosamines has been developed using
      TBHP as the oxidant. The mild catalytic system succeeded in cleaving the carbon
      nitrogen bond in nitromethane. This methodology uses commercially available,
      inexpensive catalysts and oxidants and has a wide substrate scope and operational
      simplicity. 

PMID- 24128014
TI  - Correlation between supra-sternal Doppler cardiac output (USCOM) measurements and
      chest radiological features.
AB  - Cardiac output can be measured non-invasively using supra-sternal Doppler (USCOM,
      Sydney, NSW, Australia). However, scanning can be difficult in practice in older
      patients, the reason for which has not been elucidated previously. Chest
      radiographs from 60 previously studied anaesthetised patients were reviewed and
      scored for aortic unfolding, enlargement and calcification, and cardiac
      enlargement. Corresponding supra-sternal Doppler scans were graded as easy or
      difficult using the Cattermole scoring system. Twenty patients who were difficult
      to scan, aged 60-88 years, had mean (SD) radiological scores of 5.9 (2.5) out of
      12, while 20 adult controls, 40-60 years, and 20 older patients who were easy to
      scan, 60-80 years, had radiological scores of 0.9 (1.1) and 1.7 (1.4),
      respectively (p < 0.001). Over 75% of the patients who were difficult to scan had
      two or more radiological features suggestive of aortic unfolding and cardiac
      enlargement. Morphological or anatomical changes associated with ageing within
      the upper chest play an important part in the success of using supra-sternal
      Doppler in older patients.

PMID- 24128013
TI  - Molecular analysis of subtilase cytotoxin genes of food-borne Shiga toxin
      producing Escherichia coli reveals a new allelic subAB variant.
AB  - BACKGROUND: The open reading frames of subAB genes and their flanking regions of
      18 food-borne Shiga toxin-producing E. coli (STEC) strains were analyzed.
      RESULTS: All but one subAB open reading frames (ORF) were complete in all STEC
      strains. The subAB1 genes of nine STEC strains were located on large plasmids.
      The subAB2 allele (here designated subAB2-1), which was recently described by
      others to be present in the Subtilase-Encoding PAI (SE-PAI) was found in 6 STEC
      strains. A new chromosomal subAB2 variant, designated subAB2-2 was detected in 6
      strains and was linked to a chromosomal gene hypothetically encoding an outer
      membrane efflux protein (OEP). Three STEC strains contained both subAB2 variants.
      DNA analysis indicated sequence conservation in the plasmid-located alleles and
      sequence heterogeneity among the chromosomal subAB2 genes. CONCLUSIONS: The
      results of this study have shown that 18 subAB-PCR positive STEC strains contain
      complete subAB open reading frames. Furthermore, the new allelic variant subAB2-2
      was described, which can occur in addition to subAB2-1 on a new chromosomal
      locus.

PMID- 24128015
TI  - 'Foiling' pulse oximetry interference.

PMID- 24128016
TI  - Sugammadex in anticipated difficult airways(1.).

PMID- 24128017
TI  - Sugammadex in anticipated difficult airways(2.).

PMID- 24128018
TI  - Sugammadex in anticipated difficult airways(3.).

PMID- 24128019
TI  - Sugammadex in anticipated difficult airways(4.).

PMID- 24128020
TI  - Sugammadex in anticipated difficult airways(5.).

PMID- 24128021
TI  - A reply.

PMID- 24128022
TI  - Preservative-free bicarbonate for epidural top-up(1.).

PMID- 24128023
TI  - Preservative-free bicarbonate for epidural top-up(3.).

PMID- 24128024
TI  - Preservative-free bicarbonate for epidural top-up(2.).

PMID- 24128025
TI  - A reply.

PMID- 24128026
TI  - 'Unbalanced' anaesthesia and a non-isolated forearm technique?

PMID- 24128027
TI  - A reply.

PMID- 24128028
TI  - Evaluation of oxygen concentrators.

PMID- 24128029
TI  - Does STOP-BANG really predict postoperative critical care admission?

PMID- 24128030
TI  - A reply.

PMID- 24128031
TI  - Re-introduction of the Eschmann Tracheal Tube Introducer.

PMID- 24128032
TI  - Intracuff pressure comparison between ProSeal((r)) and Supreme((r)) laryngeal
      mask airways.

PMID- 24128033
TI  - Speed of onset of spinal vs general anaesthesia for caesarean section.

PMID- 24128034
TI  - Good communication and outcome after anaesthesia.

PMID- 24128035
TI  - Knots to secure airway devices.

PMID- 24128036
TI  - Associations among attachment, sexuality, and marital satisfaction in adult
      Chilean couples: a linear hierarchical models analysis.
AB  - This study aimed to explore the associations among attachment system type, sexual
      satisfaction, and marital satisfaction in adult couples in stable relationships.
      Participants were 294 couples between the ages of 20 and 70 years who answered
      self-administered questionnaires. Hierarchical linear modeling revealed that the
      anxiety and avoidance, sexual satisfaction, and marital satisfaction dimensions
      were closely related. Specifically, the avoidance dimension, but not the anxiety
      dimension, corresponded to lower levels of sexual and marital satisfaction.
      Moreover, for the sexual satisfaction variable, an interaction effect was
      observed between the gender of the actor and avoidance of the partner, which was
      observed only in men. In the marital satisfaction dimension, effects were
      apparent only at the individual level; a positive relation was found between the
      number of years spent living together and greater contentment with the
      relationship. These results confirm the hypothetical association between
      attachment and sexual and marital satisfaction and demonstrate the relevance of
      methodologies when the unit of analysis is the couple.

PMID- 24128037
TI  - How do tablet properties influence swallowing behaviours?
AB  - OBJECTIVES: Behavioural performance of tablet swallowing was evaluated with
      different tablet conditions in terms of size, number and surface coating.
      METHODS: Four different types of tablets were prepared: small or large, and with
      or without a surface coating. Fourteen normal male adults were instructed to
      swallow the prepared tablets with 15 ml of water. The number of tablets in one
      trial was changed from one to three. To evaluate swallowing and tablet transport,
      electromyographic activity was recorded in the left suprahyoid muscles, and
      videofluorographic images were examined. KEY FINDINGS: All tablet conditions
      (size, number and surface coating) affected the swallowing performance in terms
      of total number of swallows, electromyographic burst patterns and location of
      remaining tablets. Increases in the size and number of tablets increased the
      number of swallows and electromyographic burst area and duration. In addition,
      all of these parameters increased while swallowing tablets without a coating
      compared with tablets with a coating. Location of the remaining tablets was
      mainly within the mouth. CONCLUSIONS: This study only clarified the normal
      pattern of tablet swallowing under several conditions in healthy subjects, but
      the results may facilitate comprehensive evaluation and treatment planning in
      terms of administering medication to dysphagic patients.

PMID- 24128038
TI  - Trends in adolescent sexual behavior, impact of information, and attitudes about
      HIV/AIDS in Portugal.
AB  - There is a recent decline in HIV in a significant number of countries due to the
      adoption of preventive sexual behaviors, which demonstrates that HIV reduction is
      possible. The goal of this research was to deepen knowledge of preventive sexual
      behavior in adolescents, including knowledge and attitudes about HIV/AIDS, and
      assessing whether they changed from 2002 to 2010. Data were collected through a
      self-administered questionnaire from the Portuguese sample of the Health Behavior
      in School-aged Children, a collaborative WHO study. The study provided national
      representative data of 10,587 Portuguese adolescents attending 8th and 10th
      grade. In terms of preventive behaviors, results showed an increasing trend
      regarding the percentage reporting first sexual intercourse at 14 years old or
      more and condom use at last intercourse and a stabilized trend concerning having
      had intercourse, contraceptive pill use at last intercourse and having had
      intercourse under the influence of alcohol or drugs. Nevertheless, results showed
      a systematic decreasing trend in terms of knowledge and attitudes. This suggested
      that sex education programs are still too limited to teaching sessions, strongly
      homogenized in their content and inadequate to enhance knowledge and attitudes
      regarding HIV, let alone personal and social skills of different target groups.

PMID- 24128039
TI  - Lingzhiols, unprecedented rotary door-shaped meroterpenoids as potent and
      selective inhibitors of p-Smad3 from Ganoderma lucidum.
AB  - (+)-Lingzhiol and (-)-lingzhiol, a pair of rotary door-shaped meroterpenoidal
      enantiomers, were isolated from Ganoderma lucidum. Their structures were
      identified by spectroscopic methods and X-ray diffraction crystallography.
      Lingzhiol bears an unusual 5/5/6/6 ring system characteristic of sharing a C-3'-C
      7' axis. Biological evaluation showed that (+)-lingzhiol or (-)-lingzhiol could
      selectively inhibit the phosphorylation of Smad3 in TGF-beta1-induced rat renal
      proximal tubular cells and activate Nrf2/Keap1 in mesangial cells under diabetic
      conditions. 

PMID- 24128040
TI  - Haplotype C of growth hormone (GH) gene in Japanese Black cattle: structure of GH
      protein and a novel method for detection of the gene.
AB  - From a series of studies on single nucleotide polymorphisms (SNPs) in the bovine
      growth hormone (GH) gene of Japanese Black cattle, the type-C (127(Val) and
      172(Met) ) that is specific for this breed has been intensively focused upon
      because of the economic importance for carcass traits, such as intramuscular
      oleic acid contents. In the present study, we intended to analyze the 3-D
      structure of GH of haplotype C, and developed a novel method to detect the type C
      gene. Three-D analysis of the type C protein showed that the amino acid residues
      (127(Val) and 172(Met) ), which are present in the third and fourth helixes,
      respectively, and are important for binding with GH receptors, are shifted to
      deeper positions in the molecule compared with that for type A (127(Leu) and
      172(Thr) ), implying the alteration of binding interaction with receptors. A
      novel, efficient and cost-effective method (Dot-blot-SNP technique) for type C
      genotyping was successfully established, of which the basal method was a reported
      genotyping of SNPs for a large number of plants, reducing the cost to 10% or less
      of direct sequencing. 

PMID- 24128041
TI  - Diminished time-based, but undiminished event-based, prospective memory among
      intellectually high-functioning adults with autism spectrum disorder: relation to
      working memory ability.
AB  - OBJECTIVE: Prospective memory (PM) is the ability to remember to carry out an
      intended action. Working memory is the ability to store information in mind while
      processing potentially distracting information. The few previous studies of PM in
      autism spectrum disorder (ASD) have yielded inconsistent findings. Studies of
      working memory ability in ASD have suggested a selective impairment of "visual
      working memory." However, it remains unclear whether any such impairment is the
      result of diminished (domain-specific; visual/verbal) storage capacity or
      diminished (domain-general) processing capacity. We aim to clarify these issues
      and explore the relation between PM and working memory in ASD. METHOD: Seventeen
      adults with ASD and 17 age- and IQ-matched comparison participants completed
      experimental measures of both event-based (perform action x when event y occurs)
      and time-based (perform action a at time b) PM, plus a self-report measure of PM
      skills. Participants also completed a working memory test battery. RESULTS:
      Participants with ASD self-reported diminished PM skill, and showed diminished
      performance on the time-based, but not event-based, PM task. On the working
      memory test battery, visual but not verbal storage capacity was diminished among
      participants with ASD, as was processing ability. Whereas visual storage was
      associated with event-based PM task performance among comparison participants,
      verbal storage was associated among ASD participants. CONCLUSIONS: ASD appears to
      involve a selective deficit in time-based PM and a selective difficulty with
      aspects of working memory that depend on the storage of visual information.
      However, event-based PM may be achieved through compensatory strategies in ASD.

PMID- 24128043
TI  - Structural and biochemical characterization of a bifunctional ketoisomerase/N
      acetyltransferase from Shewanella denitrificans.
AB  - Unusual N-acetylated sugars have been observed on the O-antigens of some Gram
      negative bacteria and on the S-layers of both Gram-positive and Gram-negative
      bacteria. One such sugar is 3-acetamido-3,6-dideoxy-alpha-d-galactose or Fuc3NAc.
      The pathway for its production requires five enzymes with the first step
      involving the attachment of dTMP to glucose-1-phosphate. Here, we report a
      structural and biochemical characterization of a bifunctional enzyme from
      Shewanella denitificans thought to be involved in the biosynthesis of dTDP
      Fuc3NAc. On the basis of a bioinformatics analysis, the enzyme, hereafter
      referred to as FdtD, has been postulated to catalyze the third and fifth steps in
      the pathway, namely, a 3,4-keto isomerization and an N-acetyltransferase
      reaction. For the X-ray analysis reported here, the enzyme was crystallized in
      the presence of dTDP and CoA. The crystal structure shows that FdtD adopts a
      hexameric quaternary structure with 322 symmetry. Each subunit of the hexamer
      folds into two distinct domains connected by a flexible loop. The N-terminal
      domain adopts a left-handed beta-helix motif and is responsible for the N
      acetylation reaction. The C-terminal domain folds into an antiparallel flattened
      beta-barrel that harbors the active site responsible for the isomerization
      reaction. Biochemical assays verify the two proposed catalytic activities of the
      enzyme and reveal that the 3,4-keto isomerization event leads to the inversion of
      configuration about the hexose C-4' carbon. 

PMID- 24128044
TI  - Can mandibular bone resorption predict hip fracture in elderly women? A
      systematic review of diagnostic test accuracy.
AB  - OBJECTIVES: The aim of this systematic review was to determine the diagnostic
      accuracy of the mandibular cortical width measurements and porosity in detecting
      hip osteoporosis. BACKGROUND: All of the included studies used measurements on
      panoramic radiographs. MATERIALS AND METHODS: Studies were included if they
      compared the radiographic measurements (or index tests) with central dual energy
      X-ray absorptiometry (DXA) of the hip as the reference standard. A measure of
      diagnostic accuracy such as sensitivity and specificity or area under the
      receiver operating characteristic curve was also required for inclusion. RESULTS:
      Seven studies were identified. Meta-analysis was not possible because of the
      heterogeneity of the studies. The studies all demonstrated moderate diagnostic
      accuracy. CONCLUSION: If a patient with a thin or porous mandibular cortex is
      identified by a chance radiographic finding, additional clinical risk factors
      need to be considered and the patient referred for further investigation with DXA
      where necessary.

PMID- 24128045
TI  - Clinical allergy. Managing generalized interferon-induced eruptions and the
      effectiveness of desensitization.
AB  - BACKGROUND: We evaluated the value of skin tests and the efficacy of a 12-step
      desensitization protocol to pegylated interferon (IFN) in patients with
      generalized drug eruptions due to IFNs. METHODS: A retrospective study (1998
      2009) was followed by a cross-sectional clinical study conducted prospectively
      (2009-2011). All patients received a dermatological clinical examination and skin
      tests. Twelve-step IFN desensitization was proposed for patient with active
      hepatitis C and no alternative therapy. RESULTS: Twenty-six patients (13 males,
      mean age, 53.5 years) had generalized reactions to IFNs; 21 were treated with IFN
      alpha and 5 with IFN-beta. Moreover, 21 patients had skin tests. Intradermal
      tests (IDTs) were positive after an average of 72 h. Cross-reactivity between peg
      IFN-alpha2a and peg-IFN-alpha2b was observed in 5/10 cases in the prospective
      study. In 16 of 26 cases, IFN treatment was stopped. In 8 of 16 cases of diffuse
      eczematous drug eruption, treatment was continued. The corticosteroid and
      antihistamine were sufficient in 4/8 cases. In three other cases, topical
      tacrolimus was highly effective. In 3 of 16 cases in which treatment were
      stopped, patients underwent the early resumption of peg-IFN-alpha. These three
      patients had positive tests with peg-IFN-alpha2a and peg-IFN-alpha2b and
      successfully completed the tolerance induction protocol for peg-IFN-alpha2b.
      Tolerance induction involved a weekly dose of peg-IFN and a gradual increase in
      the recovery of an antiviral C. Clinical tolerance was excellent, and the
      patients' viral load C became negative. CONCLUSIONS: Our study demonstrates the
      benefit of allergy testing in cases of generalized drug reactions to IFN, cross
      reactivities in a single class of IFNs and the importance of delayed IDT reading.
      We report for the first time the effectiveness of 12-step desensitization with
      peg-IFN.

PMID- 24128047
TI  - Trophic shift, not collapse.

PMID- 24128046
TI  - Oridonin ring A-based diverse constructions of enone functionality:
      identification of novel dienone analogues effective for highly aggressive breast
      cancer by inducing apoptosis.
AB  - Oridonin (1) has attracted considerable attention in recent years because of its
      unique and safe anticancer pharmacological profile. Nevertheless, it exhibits
      moderate to poor effects against highly aggressive cancers including triple
      negative and drug-resistant breast cancer cells. Herein, we report the rational
      design and synthesis of novel dienone derivatives with an additional alpha,beta
      unsaturated ketone system diversely installed in the A-ring based on this class
      of natural scaffold that features dense functionalities and stereochemistry-rich
      frameworks. Efficient and regioselective enone construction strategies have been
      established. Meanwhile, a unique 3,7-rearrangement reaction was identified to
      furnish an unprecedented dienone scaffold. Intriguingly, these new analogues have
      been demonstrated to significantly induce apoptosis and inhibit colony formation
      with superior antitumor effects against aggressive and drug-resistant breast
      cancer cells in vitro and in vivo while also exhibiting comparable or lower
      toxicity to normal human mammary epithelial cells in comparison with 1. 

PMID- 24128048
TI  - Heredity of restless legs syndrome in a pregnant population.
AB  - OBJECTIVE: To synthesize published research on genetic and heredity findings
      related to restless legs syndrome (RLS) in a pregnant population. DATA SOURCES:
      PubMed, CINAHL, and PsycINFO databases and reference lists from published
      articles. STUDY SELECTION: Literature searches were conducted for primary
      research studies published in English on the genetic and heredity findings of RLS
      in pregnant populations. DATA EXTRACTION: Study characteristics and findings
      related to genetic and heredity aspects of RLS in a pregnant population. DATA
      SYNTHESIS: Five data-based articles met the criteria for study inclusion. Study
      findings comprised Level-2 and Level-3 evidence. Four of the five studies were
      larger population studies and contained a subset of pregnant participants. Parity
      and family history were important predictors of RLS proband status. Probands
      reported symptoms were often initiated during or after pregnancy. CONCLUSIONS:
      Symptoms of RLS for female probands are often initiated during pregnancy or after
      childbirth. A history of RLS in a previous pregnancy and family history of RLS
      were strong predictors of RLS in the current pregnancy. Future research on
      genetic associations of RLS in pregnancy is warranted.

PMID- 24128049
TI  - Factors associated with oral hygiene practices among adults with systemic
      sclerosis.
AB  - OBJECTIVE: To identify factors associated with oral hygiene practices in adults
      with systemic sclerosis (SSc). METHODS: In this cross-sectional study, 178
      dentate adults with SSc received an oral examination which included measurement
      of oral aperture, assessment of manual dexterity to perform oral hygiene, as well
      as completion of the Center of Epidemiological Studies Depression (CES-D) Scale
      and an oral health-related questionnaire. RESULTS: Multivariable logistic
      regression modelling showed male, minority and high CES-D scores (i.e. clinically
      significant symptoms of depression) were associated with less likelihood of
      participants brushing teeth at least twice daily, but the presence of self
      reported dry mouth symptoms increased the likelihood of toothbrushing. Having a
      dental visit in the past 12 months and use of an adapted flossing or interdental
      cleaning device were significantly associated with daily dental flossing;
      however, having difficulty flossing teeth reduced the likelihood of daily
      flossing. CONCLUSIONS: Overall, demographic variables were strongly associated
      with toothbrushing frequency, whereas flossing self-efficacy and barriers were
      strongly associated with dental flossing frequency in adults with SSc. The
      results suggest that dental health professionals should take mental health into
      consideration when educating patients with SSc to improve their oral hygiene and
      consider making referrals for patients exhibiting suspected clinically
      significant depressive symptoms to mental health professionals for further
      evaluation and treatment. In addition, an appropriate adapted flossing or
      interdental cleaning device should be recommended to increase dental flossing
      practices in this patient population.

PMID- 24128050
TI  - In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions:
      potential role of antioxidants.
AB  - Over the last decades, oxidative stress has been described as a deleterious
      phenomenon contributing to numerous noncommunicable diseases such as
      cardiovascular disease, diabetes, and cancers. As many authors ascribed the
      healthy effect of fruit and vegetable consumption mainly to their antioxidant
      contents, it has been hypothesized that their protection could occur from the
      gut. Therefore, the aim of this study was to develop an original and
      physiological model of nanoemulsions to study lipid peroxidation within the
      intestine and to assess the properties of potential antioxidants in this setting.
      Several nanoemulsions were compared in terms of physical characteristics and
      reactivity to 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced
      oxidation. Formulations included different types of lipids, a detergent (a
      conjugated bile salt or sodium dodecyl sulfate) and, finally, lipophilic
      antioxidants. Hemin and myoglobin were also tested as relevant potential
      oxidants. Fatty acid (FA) peroxidation was monitored by gas chromatography while
      malondialdehyde and antioxidant contents were measured by HPLC. Investigated
      nanoemulsions were composed of spherical or cylindrical mixed micelles, the
      latter being the least resistant to oxidation. In the experimental conditions,
      AAPH was the only efficient oxidant. Alpha-tocopherol and lutein significantly
      slowed FA degradation from 4 to 1 MUM, respectively. On the contrary, beta
      carotene did not show any protective capacity at 4 MUM. In conclusion, the tested
      nanoemulsions were appropriate to assess antioxidant capacity during the
      intestinal phase of digestion.

PMID- 24128051
TI  - Gemcitabine sensitizes lung cancer cells to Fas/FasL system-mediated killing.
AB  - Gemcitabine is a chemotherapy agent commonly used in the treatment of non-small
      cell lung cancer (NSCLC) that has been demonstrated to induce apoptosis in NSCLC
      cells by increasing functionally active Fas expression. The aim of this study was
      to evaluate the Fas/Fas ligand (FasL) system involvement in gemcitabine-induced
      lung cancer cell killing. NSCLC H292 cells were cultured in the presence or
      absence of gemcitabine. FasL mRNA and protein were evaluated by real-time PCR,
      and by Western blot and flow cytometry, respectively. Apoptosis of FasL
      expressing cells was evaluated by flow cytometry, and caspase-8 and caspase-3
      activation by Western blot and a colorimetric assay. Cytotoxicity of lymphokine
      activated killer (LAK) cells and malignant pleural fluid lymphocytes against H292
      cells was analysed in the presence or absence of the neutralizing anti-Fas ZB4
      antibody, by flow cytometry. Gemcitabine increased FasL mRNA and total protein
      expression, the percentage of H292 cells bearing membrane-bound FasL (mFasL) and
      of mFasL-positive apoptotic H292 cells, as well as caspase-8 and caspase-3
      cleavage. Moreover, gemcitabine increased CH11-induced caspase-8 and caspase-3
      cleavage and proteolytic activity. Cytotoxicity of LAK cells and pleural fluid
      lymphocytes was increased against gemcitabine-treated H292 cells and was
      partially inhibited by ZB4 antibody. These results demonstrate that gemcitabine:
      (i) induces up-regulation of FasL in lung cancer cells triggering cell apoptosis
      via an autocrine/paracrine loop; (ii) induces a Fas-dependent apoptosis mediated
      by caspase-8 and caspase-3 activation; (iii) enhances the sensitivity of lung
      cancer cells to cytotoxic activity of LAK cells and malignant pleural fluid
      lymphocytes, partially via Fas/FasL pathway. Our data strongly suggest an active
      involvement of the Fas/FasL system in gemcitabine-induced lung cancer cell
      killing.

PMID- 24128052
TI  - The mediating effect of severity of client aggression on burnout between hospital
      inpatient and community residential staff who support adults with intellectual
      disabilities.
AB  - AIMS AND OBJECTIVES: To compare exposure to client aggressive behaviour,
      perceived self-efficacy in managing this behaviour and burnout between community
      residential group home and specialised hospital inpatient staff who provide care
      for adults with intellectual disabilities (ID). To assess the mediating role of
      aggression exposure on burnout in these two staff groups. BACKGROUND: Aggressive
      behaviour is a common indication for admission to hospital so these staff
      typically experience more frequent and severe forms compared to staff working in
      the community. There have been mixed results in few studies examining burnout and
      perceived self-efficacy between these two groups. DESIGN: This study used a
      demographically matched sample of cross-sectional survey data from community
      residential group home and hospital staff who care for adults with ID in Ontario,
      Canada. METHODS: Exposure to aggression, perceived self-efficacy and burnout were
      compared for 42 matched pairs using descriptive statistics. A mediation analysis
      was used to examine the role of aggression severity in the relationship between
      care setting and burnout. RESULTS: Hospital staff were exposed to more severe
      client aggression and scored higher in emotional exhaustion (EE). There were no
      differences in perceived self-efficacy. Severity of aggression was a partial
      mediator of the higher EE among hospital staff. CONCLUSIONS: Exposure to more
      severe forms of client aggression among hospital staff contributes, at least in
      part, to them feeling more emotionally exhausted. This study contributes to
      further understanding exposure to aggression in these different settings and the
      impact it can have on emotional outcomes. RELEVANCE TO CLINICAL PRACTICE: There
      may be a role for policy and resource development aimed at reducing aggression
      and preventing or managing the associated emotional consequences. This is
      particularly true in hospitals, where aggression is most severe.

PMID- 24128053
TI  - Molecular identification of cryptic bumblebee species from degraded samples using
      PCR-RFLP approach.
AB  - The worldwide decline and local extinctions of bumblebees have raised a need for
      fast and accurate tools for species identification. Morphological characters are
      often not sufficient, and molecular methods have been increasingly used for
      reliable identification of bumblebee species. Molecular methods often require
      high-quality DNA which makes them less suitable for analysis of low-quality or
      older samples. We modified the PCR-RFLP protocol for an efficient and cost
      effective identification of four bumblebee species in the subgenus Bombus s. str.
      (B. lucorum, B. terrestris, B. magnus and B. cryptarum). We used a short partial
      mitochondrial COI fragment (446 bp) and three diagnostic restriction enzymes
      (Hinf I, Hinc II and Hae III) to identify species from degraded DNA material.
      This approach allowed us to efficiently determine the correct species from all
      degraded DNA samples, while only a subset of samples 64.6% (31 of 48) resulted in
      successful amplification of a longer COI fragment (1064 bp) using the previously
      described method. This protocol can be applied for conservation and management of
      bumblebees within this subgenus and is especially useful for fast species
      identification from degraded samples. 

PMID- 24128054
TI  - Mucosal reactive oxygen species are required for antiviral response: role of Duox
      in influenza a virus infection.
AB  - AIMS: Influenza A virus (IAV), a major airborne pathogen, is closely associated
      with significant morbidity and mortality. The primary target for influenza virus
      replication is the respiratory epithelium, which reacts to infection by mounting
      a multifaceted antiviral response. A part of this mucosal host defense is the
      generation of reactive oxygen species (ROS) by NADPH oxidases. Duox1 and Duox2
      are the main ROS-producing enzymes in the airway epithelium, but their
      contribution to mammalian host defense is still ill defined. RESULTS: To gain a
      better understanding of Duox function in respiratory tract infections, human
      differentiated lung epithelial cells and an animal model were used to monitor the
      effect of epithelial ROS on IAV propagation. IAV infection led to coordinated up
      regulation of Duox2 and Duox-mediated ROS generation. Interference with H2O2
      production and ROS signaling by oxidase inhibition or H2O2 decomposition
      augmented IAV replication. A nuclear pool of Duox enzymes participated in the
      regulation of the spliceosome, which is critical for alternative splicing of
      viral transcripts and controls the assembly of viable virions. In vivo silencing
      of Duox increased the viral load on intranasal infection with 2009 pandemic H1N1
      influenza virus. INNOVATION: This is the first study conclusively linking Duox
      NADPH oxidases with the antiviral mammalian immune response. Further, ROS
      generated by Duox enzymes localized adjacent to nuclear speckles altered the
      splicing of viral genes. CONCLUSION: Duox-derived ROS are host protective and
      essential for counteracting IAV replication.

PMID- 24128055
TI  - The effect of extension and loading of the carpus on radial rotation.
AB  - OBJECTIVE: To describe the direction and magnitude of the rotation of the radius
      relative to the ulna during extension of the carpus and to describe the effect of
      carpal extension on internal and external rotation of the radius relative to the
      ulna. STUDY DESIGN: In vitro experiment. ANIMALS: Cadaveric canine thoracic limbs
      (n = 11). METHODS: Eleven thoracic limbs were collected from 6 healthy mixed
      breed dogs of medium build. Each specimen was radiographed to ensure that the
      carpal and elbow joints were free of pathology. The elbow joint was
      disarticulated and the distal thoracic limb was prepared for biomechanical
      testing. Each specimen was stripped of soft tissue, leaving the soft tissues
      around the proximal aspect of the radius and ulna intact. The interosseous
      ligament, pronator teres muscle, and all the soft tissues distal to the distal
      metaphysis of the radius were also left intact. In the 1st part of the study, the
      rotation of the radius relative to the ulna was measured while extending the
      carpal joint using a system of weights and pulleys attached to the manus. In the
      2nd part of the study, the internal and external rotation of the radius relative
      to the ulna was performed by applying an internal and external rotational load to
      the radius using a system of weights and pulleys attached to the radius. The
      internal and external rotation of the radius was measured with the carpus
      unloaded and with the carpus extended by applying a load of 5 kg to the manus.
      RESULTS: Extension of the carpus resulted in internal rotation of the radius
      relative to the ulna. With the carpus extended under a maximum load of 2 kg, the
      mean (+/- SD) internal rotation of the radius was 4.3 +/- 2.1 degrees  for all
      specimens. With the carpus unloaded, the mean internal and external rotation of
      the radius was 11.5 +/- 2.9 degrees  and 22.5 +/- 7.7 degrees  for all specimens,
      respectively. With the carpus loaded (extended under 5 kg load), the mean
      internal and external rotation of the radius was 3.3 +/- 1.2 degrees  and 7.3 +/-
      2.0 degrees  for all specimens, respectively. The difference between internal and
      external rotation with the carpus loaded and unloaded was significant.
      CONCLUSION: Extending the carpus results in internal rotation, and proximal
      translation of the radius relative to the ulna. Loading the carpus in extension
      decreases the internal and external rotation of the radius relative to the ulna.
      A better understanding of the interaction between the carpus and the elbow may
      improve our understanding of the pathogenesis of elbow dysplasia.

PMID- 24128056
TI  - Superannuation retirement balances: a surprising outcome.
AB  - AIM: Although the guaranteed superannuation system is believed by many to provide
      a safe and adequate source of funds in retirement, some will be unpleasantly
      surprised. The aim of this paper is to demonstrate the significant effect of the
      economic cycle on the final accumulated balance in superannuation retirement
      accounts. METHOD: A Monte Carlo simulation is used to illustrate the variance in
      outcomes that can be expected for a hypothetical individual. RESULTS: The
      expected accumulated superannuation balances for two hypothetical individuals are
      estimated. The spread of outcomes is used to illustrate the problem of using only
      the mean of the distribution as a predictor of wealth in the retirement years.
      CONCLUSIONS: Many retirees rely on superannuation to fund their retirement.
      However regular contributions to superannuation does not ensure a predictable
      outcome, and active management of contributions is required if retirement goals
      are to be met.

PMID- 24128057
TI  - Copper(I)/ABNO-catalyzed aerobic alcohol oxidation: alleviating steric and
      electronic constraints of Cu/TEMPO catalyst systems.
AB  - Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically
      unhindered primary alcohols and electronically activated substrates, but they
      show reduced reactivity with aliphatic and secondary alcohols. Here, we report a
      catalyst system, consisting of ((MeO)bpy)Cu(I)(OTf) and ABNO ((MeO)bpy = 4,4'
      dimethoxy-2,2'-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that
      mediates aerobic oxidation of all classes of alcohols, including primary and
      secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency.
      The catalyst exhibits broad functional group compatibility, and most reactions
      are complete within 1 h at room temperature using ambient air as the source of
      oxidant.

PMID- 24128058
TI  - Professional exposure to basaltic rock dust: assessment by the Vibrio fischeri
      ecotoxicological test.
AB  - BACKGROUND: A recent study demonstrates that inhalation of airborne particulate
      from Mount Etna eruptions may induce fibrotic lung disease. The occupational
      exposure of construction workers from the Etna area, who excavate building sites
      and use basalt dust to make mortar, has never been assessed. METHODS: Samples of
      basalt, volcanic ash, basalt + cement and cement dust were collected on the
      construction site of a subway tunnel, ground to dust and subjected to the
      Microtox((r)) solid-phase test to evaluate the toxicity of dust suspensions.
      Samples were investigated by scanning electron microscopy equipped with energy
      dispersive X-ray analysis (EDX). Minerals were identified and characterized by
      their morphology and elemental composition. RESULTS: The elements found most
      frequently were C, Na, Mg, Al, Si, K, Ca, Ti, Mn, Fe and O. All four dusts were
      toxic: basalt and ash were significantly less toxic than basalt + cement and
      cement, which shared a similar and very high degree of toxicity. Higher Fe, Ca
      and Mg concentrations were associated with greater toxicity. CONCLUSIONS: The
      risk related to long-term occupational exposure to various dusts on constructions
      sites in the Mount Etna area should be further assessed.

PMID- 24128059
TI  - A logistic normal multinomial regression model for microbiome compositional data
      analysis.
AB  - Changes in human microbiome are associated with many human diseases. Next
      generation sequencing technologies make it possible to quantify the microbial
      composition without the need for laboratory cultivation. One important problem of
      microbiome data analysis is to identify the environmental/biological covariates
      that are associated with different bacterial taxa. Taxa count data in microbiome
      studies are often over-dispersed and include many zeros. To account for such an
      over-dispersion, we propose to use an additive logistic normal multinomial
      regression model to associate the covariates to bacterial composition. The model
      can naturally account for sampling variabilities and zero observations and also
      allow for a flexible covariance structure among the bacterial taxa. In order to
      select the relevant covariates and to estimate the corresponding regression
      coefficients, we propose a group l1 penalized likelihood estimation method for
      variable selection and estimation. We develop a Monte Carlo expectation
      maximization algorithm to implement the penalized likelihood estimation. Our
      simulation results show that the proposed method outperforms the group l1
      penalized multinomial logistic regression and the Dirichlet multinomial
      regression models in variable selection. We demonstrate the methods using a data
      set that links human gut microbiome to micro-nutrients in order to identify the
      nutrients that are associated with the human gut microbiome enterotype. 

PMID- 24128061
TI  - Palladacycle-catalyzed methylenecyclopropanation of bicyclic alkenes with
      propiolates.
AB  - An efficient way to access functionalized methylenecyclopropanes has been
      developed by palladacycle-catalyzed cyclopropanation of bicyclic alkenes with
      propiolates in high yields. The structure of the palladacycle was kept intact in
      the reaction, shown by (31)P NMR spectrum studies. A rational mechanism has been
      proposed with a deuterium-labeled experiment. The usefulness of the
      functionalized methylenecyclopropanes has also been demonstrated. 

PMID- 24128060
TI  - PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum
      usitatissimum L.) mutant population and TILLinG platform for forward and reverse
      genetics.
AB  - BACKGROUND: Flax (Linum usitatissimum L.) is an economically important fiber and
      oil crop that has been grown for thousands of years. The genome has been recently
      sequenced and transcriptomics are providing information on candidate genes
      potentially related to agronomically-important traits. In order to accelerate
      functional characterization of these genes we have generated a flax EMS mutant
      population that can be used as a TILLinG (Targeting Induced Local Lesions in
      Genomes) platform for forward and reverse genetics. RESULTS: A population of
      4,894 M2 mutant seed families was generated using 3 different EMS concentrations
      (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping
      and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and
      1,552 families (38.5%) showed a visual developmental phenotype (stem size and
      diameter, plant architecture, flower-related). The majority of these families
      showed more than one phenotype. Mutant phenotype data are organised in a database
      and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb).
      Preliminary screens were also performed for atypical fiber and seed phenotypes.
      Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for
      subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to
      validate the collection for reverse genetics, DNA pools were screened for two
      genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase
      (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations
      in the C3H and CAD genes, respectively. The average mutation rate was calculated
      as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five
      out of the 52 flax cad mutant families containing missense or codon stop
      mutations showed the typical orange-brown xylem phenotype observed in CAD down
      regulated/mutant plants in other species. CONCLUSIONS: We have developed a flax
      mutant population that can be used as an efficient forward and reverse genetics
      tool. The collection has an extremely high mutation rate that enables the
      detection of large numbers of independant mutant families by screening a
      comparatively low number of M2 families. The population will prove to be a
      valuable resource for both fundamental research and the identification of
      agronomically-important genes for crop improvement in flax.

PMID- 24128062
TI  - Evaluation of the perinatal grief intensity scale in the subsequent pregnancy
      after perinatal loss.
AB  - OBJECTIVES: To evaluate the reliability and validity of the Perinatal Grief
      Intensity Scale (PGIS) for identifying a woman's grief intensity in the immediate
      subsequent pregnancy after a miscarriage, stillbirth, or neonatal death.
      DESIGN/SETTING/PARTICIPANTS: A web-based approach was used to collect data from
      227 pregnant women after each woman had experienced a perinatal loss in her
      previous pregnancy. METHODS: Participants completed a demographic information
      form and the 14-item PGIS. RESULTS: Cronbach's alphas for the PGIS total scale
      and subscales were high: 0.75 (PGIS total), 0.80 (Reality), 0.82 (Confront
      Others), and 0.80 (Congruence), which indicated good internal consistency
      reliability. Validity was supported by factor analysis of the PGIS, which
      accounted for 66.94% of the total variance. Mothers in the neonatal death group
      experienced more intense grief, as measured by the PGIS, when compared with
      mothers in the miscarriage or stillbirth groups. CONCLUSIONS: Data from this
      study provided initial support for the reliability and validity of the PGIS in
      women in their immediate subsequent pregnancies after perinatal loss as well as
      the concepts of the grief intensity theoretical framework.

PMID- 24128063
TI  - A Comparative Study of the Photosensitizer Penetration into Artificial Caries
      Lesions in Dentin Measured by the Confocal Raman Microscopy.
AB  - This study utilized the confocal Raman microspectroscopy (CRM) technique for the
      first time to investigate the degree of the penetration of toluidine blue-orto
      (TBO) in artificial caries lesions produced by two distinct caries-inducing
      models. The dentin specimens (n = 10) were divided into three groups: control, in
      vitro and in situ. Thereafter, the lesion depth and the demineralization level
      were evaluated by cross-sectional microhardness (CSMH). CRM mapping across the
      dentin surface was assessed after the dye application. The CSMH and CRM data were
      analyzed by t-test and ANOVA, respectively (P < 0.05). The values of the lesion
      depth and the demineralization areas were higher for in situ samples (P < 0.05).
      The TBO penetration values (MUm) for the control, in vitro and in situ groups
      were 44.8 +/- 5.6, 46.1 +/- 4.5 and 51.2 +/- 8.5, respectively. There were no
      statistically significant differences among the groups (P > 0.05). The rate of
      TBO penetration was detected up to about <50 MUm and the demineralization level
      did not influence the results. These results have showed promising parameters to
      develop new protocols for deep caries lesions management using photodynamic
      antimicrobial chemotherapy.

PMID- 24128064
TI  - Analysis and assay of oseltamivir-resistant mutants of influenza neuraminidase
      via direct observation of drug unbinding and rebinding in simulation.
AB  - The emergence of influenza drug resistance is a major public health concern. The
      molecular basis of resistance to oseltamivir (Tamiflu) is investigated using a
      computational assay involving multiple 500 ns unrestrained molecular dynamics
      (MD) simulations of oseltamivir complexed with mutants of H1N1-2009 influenza
      neuraminidase. The simulations, accelerated using graphics processors (GPUs), and
      using a fully explicit model of water, are of sufficient length to observe
      multiple drug unbinding and rebinding events. Drug unbinding occurs during
      simulations of known oseltamivir-resistant mutants of neuraminidase. Molecular
      level rationalizations of drug resistance are revealed by analysis of these
      unbinding trajectories, with particular emphasis on the dynamics of the mutant
      residues. The results indicate that MD simulations can predict weakening of
      binding associated with drug resistance. In addition, visualization and analysis
      of binding site water molecules reveal their importance in stabilizing the
      binding mode of the drug. Drug unbinding is accompanied by conformational
      changes, driven by the mutant residues, which results in flooding of a key pocket
      containing tightly bound water molecules. This displaces oseltamivir, allowing
      the tightly bound water molecules to be released into bulk. In addition to the
      role of water, analysis of the trajectories reveals novel behavior of the
      structurally important 150-loop. Motion of the loop, which can move between an
      open and closed conformation, is intimately associated with drug unbinding and
      rebinding. Opening of the loop occurs coincidentally with drug unbinding, and
      interactions between oseltamivir and the loop seem to aid in the repositioning of
      the drug back into an approximation of its original binding mode on rebinding.
      The similarity of oseltamivir to a transition state analogue for neuraminidase
      suggests that the dynamics of the loop could play an important functional role in
      the enzyme, with loop closing aiding in binding of the substrate and loop opening
      aiding the release of the product. 

PMID- 24128065
TI  - Sexuality in later life: examining beliefs and perceptions of undergraduate
      students.
AB  - Understanding students' beliefs and perceptions of sex/sexuality in later life
      can reduce and prevent ageist myths and stereotypes. The objective of this study
      was to gauge undergraduate students' knowledge of several myths, stereotypes, and
      facts regarding sex/sexuality in later life, including lesbian, gay, bisexual,
      and transgendered (LGBT) older adults. More than 85% of students held a positive
      view of sex/sexuality in later life with 65% believing that they would engage in
      sexual activity past age 80 (N=125). Correct responses to true/false questions
      were higher for those with a positive perspective on aging, and recognizing that
      sexual behavior does not cease to be important with aging was the strongest
      predictor of holding a positive view on sexuality in later life. No significant
      differences were observed from responses regarding LGBT older adults or
      constraints to sexuality in long term care facilities. The positive perceptions
      among students in the current study suggest an increased acceptance of sexuality
      and diversity that should be maintained in university curricula.

PMID- 24128066
TI  - Kinetic analysis of the HBTM-catalyzed esterification of an enantiopure secondary
      alcohol.
AB  - A detailed kinetic analysis of the homobenzotetramisole-mediated esterification
      of the enantiopure secondary alcohol (1R,2S)-2-phenylcyclohexanol is presented.
      The results of this analysis show that the reaction is first order in the
      homobenzotetramisole catalyst, first order in (1R,2S)-2-phenylcyclohexanol, and
      first order in propionic anhydride. Initial rates, the turnover frequency of the
      catalyst, and "different excess" plots were utilized in this evaluation.
      Additionally, a "same excess" plot revealed no noticeable catalyst decomposition
      or product inhibition during the course of the reaction. 

PMID- 24128067
TI  - Effect of cashew nut shell liquid on metabolic hydrogen flow on bovine rumen
      fermentation.
AB  - Effect of cashew nut shell liquid (CNSL), a methane inhibitor, on bovine rumen
      fermentation was investigated through analysis of the metabolic hydrogen flow
      estimated from concentrations of short-chain fatty acids (SCFA) and methane.
      Three cows were fed a concentrate and hay diet without or with a CNSL-containing
      pellet. Two trials were conducted using CNSL pellets blended with only silica
      (trial 1) or with several other ingredients (trial 2). Methane production was
      measured in a respiration chamber system, and energy balance and nutrient
      digestibility were monitored. The estimated flow of metabolic hydrogen
      demonstrated that a part of metabolic hydrogen was used for hydrogen gas
      production, and a large amount of it flowed into production of methane and SCFA
      in both trial 1 and 2, when CNSL was administered to the bovine rumen. The
      results obtained by regression analyses showed that the effect of CNSL supply on
      methane reduction was coupled with a significant (P < 0.01) decrease of acetate
      and a significant (P < 0.01) increase of propionate and hydrogen gas. These
      findings reveal that CNSL is able to reduce methane and acetate production, and
      to increase hydrogen gas and propionate production in vivo. 

PMID- 24128068
TI  - Determination of protein-ligand binding constants of a cooperatively regulated
      tetrameric enzyme using electrospray mass spectrometry.
AB  - This study highlights the benefits of nano electrospray ionization mass
      spectrometry (nanoESI-MS) as a fast and label-free method not only for
      determination of dissociation constants (KD) of a cooperatively regulated enzyme
      but also to better understand the mechanism of enzymatic cooperativity of
      multimeric proteins. We present an approach to investigate the allosteric
      mechanism in the binding of inhibitors to the homotetrameric enzyme fructose 1,6
      bisphosphatase (FBPase), a potential therapeutic target for glucose control in
      type 2 diabetes. A series of inhibitors binding at an allosteric site of FBPase
      were investigated to determine their KDs by nanoESI-MS. The KDs determined by ESI
      MS correlate very well with IC50 values in solution. The Hill coefficients
      derived from nanoESI-MS suggest positive cooperativity. From single-point
      measurements we could obtain information on relative potency, stoichiometry,
      conformational changes, and mechanism of cooperativity. A new X-ray crystal
      structure of FBPase tetramer binding ligand 3 in a 4:4 stoichiometry is also
      reported. NanoESI-MS-based results match the current understanding of the
      investigated system and are in agreement with the X-ray structural data, but
      provide additional mechanistic insight on the ligand binding, due to the better
      dynamic resolution. This method offers a powerful approach for studying other
      proteins with allosteric binding sites, as well. 

PMID- 24128069
TI  - Nutritional assessment of patients with acute leukemia during induction
      chemotherapy: association with hospital outcomes.
AB  - Cancer-related malnutrition causes morbidity and reduced survival. The aim of
      this study was to evaluate the nutritional and inflammatory status of patients
      with acute leukemia in association with duration of neutropenic fever (DNF) and
      length of hospital stay (LHS) during induction chemotherapy. Fifty-five patients
      with acute lymphoblastic leukemia (ALL) (n = 28) and acute myeloid leukemia (AML)
      (n = 27) completed the study. There were significant differences between the two
      groups according to LHS and DNF (p = 0.022 and p = 0.012, respectively): both had
      a longer period in patients with AML. The patients were statistically different
      according to body mass index (BMI), pre-albumin, high-sensitivity C-reactive
      protein (hs-CRP) and patient-generated subjective global assessment (PG-SGA)
      score (p = 0.049, p = 0.028, p < 0.001, p = 0.030). In patients with ALL, serum
      albumin and pre-albumin levels were associated with LHS and DNF, respectively.
      Moreover, PG-SGA score was associated with DNF. In patients with AML, BMI and
      second pre-albumin level < 10 mg/dL were associated with DNF. Pre-albumin was the
      common indicator for chemotherapy-related complications in patients with both ALL
      and AML. Early nutritional assessment can help to find patients with acute
      leukemia who need nutritional support, and it may contribute to better outcome
      and less toxicity.

PMID- 24128070
TI  - Application of emerging biomarkers of acute kidney injury in development of
      kidney-sparing polypeptide-based antibiotics.
AB  - Polypeptide antibiotics, such as polymyxins and aminoglycosides, are essential
      for treatment of life-threatening Gram-negative infections. Acute kidney injury
      (AKI) attributed to treatment with these agents severely limits their clinical
      application. Because standard biomarkers (serum creatinine [sCRE] and blood urea
      nitrogen [BUN]) feature limited sensitivity, the development of novel biomarkers
      of AKI is important. Here, we compared the performance of standard and emerging
      biomarkers of AKI for the detection of nephrotoxicity caused by polymyxin B
      across multiple species (rat, dog and monkey). Further, we applied a biomarker
      driven strategy for selection of new kidney-sparing polymyxin analogs. Polymyxin
      B treatment produced dose-dependent kidney injury observed as proximal tubular
      degeneration/regeneration and necrosis across all species. Dogs and monkeys had
      similar biomarker profiles that included increases of both standard (sCRE and
      BUN) and emerging (urinary neutrophil gelatinase-associated Lipocalin [NGAL] and
      urinary kidney injury molecule 1 [KIM-1]) biomarkers of AKI. In contrast, only
      urinary NGAL and urinary KIM-1 were sufficiently capable of detecting kidney
      injury in rats. Because rats provide a feasible model for screening compounds in
      drug development, we utilized urinary NGAL as a sensitive biomarker of AKI to
      screen and rank order compounds in a 2-day toxicity study. To our knowledge, this
      study provides a first example of successfully applying biomarkers of AKI in drug
      development.

PMID- 24128071
TI  - Protective effect of intranasal immunization with Neospora caninum membrane
      antigens against murine neosporosis established through the gastrointestinal
      tract.
AB  - Neospora caninum is an Apicomplexa parasite that in the last two decades was
      acknowledged as the main pathogenic agent responsible for economic losses in the
      cattle industry. In the present study, the effectiveness of intranasal
      immunization with N. caninum membrane antigens plus CpG adjuvant was assessed in
      a murine model of intragastrically established neosporosis. Immunized mice
      presented a lower parasitic burden in the brain on infection with 5 * 10(7)
      tachyzoites, showing that significant protection was achieved by this
      immunization strategy. Intestinal IgA antibodies raised by immunization markedly
      agglutinated live N. caninum tachyzoites whereas previous opsonization with IgG
      antibodies purified from immunized mice sera reduced parasite survival within
      macrophage cells. Although an IgG1 : IgG2a ratio < 1 was detected in the
      immunized mice before and after infection, indicative of a predominant T helper
      type 1 immune response, no increased production of interferon-gamma was detected
      in the spleen or mesenteric lymph nodes of the immunized mice. Altogether, these
      results show that mucosal immunization with N. caninum membrane proteins plus CpG
      adjuvant protect against intragastrically established neosporosis and indicate
      that parasite-specific mucosal and circulating antibodies have a protective role
      against this parasitic infection.

PMID- 24128072
TI  - Effective treatment of metastatic renal cell carcinoma with topical imiquimod
      therapy.

PMID- 24128073
TI  - Back to the future: past and future era-based schematic support and associative
      memory for prices in younger and older adults.
AB  - Older adults typically display various associative memory deficits, but these
      deficits can be reduced when conditions allow for the use of prior knowledge or
      schematic support. To determine how era-specific schematic support and future
      simulation might influence associative memory, we examined how younger and older
      adults remember prices from the past as well as the future. Younger and older
      adults were asked to imagine the past or future, and then studied items and
      prices from approximately 40 years ago (market value prices from the 1970s) or 40
      years in the future. In Experiment 1, all items were common items (e.g., movie
      ticket, coffee) and the associated prices reflected the era in question, whereas
      in Experiment 2, some item-price pairs were specific to the time period (e.g.,
      typewriter, robot maid), to test different degrees of schematic support. After
      studying the pairs, participants were shown each item and asked to recall the
      associated price. In both experiments, older adults showed similar performance as
      younger adults in the past condition for the common items, whereas age-related
      differences were greater in the future condition and for the era-specific items.
      The findings suggest that in order for schematic support to be effective, recent
      (and not simply remote) experience is needed in order to enhance memory. Thus,
      whereas older adults can benefit from "turning back the clock," younger adults
      better remember future-oriented information compared with older adults, outlining
      age-related similarities and differences in associative memory and the efficient
      use of past and future-based schematic support.

PMID- 24128074
TI  - How do negative self-perceptions of aging become a self-fulfilling prophecy?
AB  - Recent studies have provided considerable evidence on long-term effects of self
      perceptions of aging (SPA) on indicators of successful aging such as health or
      life satisfaction. To date, little is known about the mechanisms underlying these
      effects. This study therefore examined whether negative SPA impair the use of
      self-regulation strategies that include selection, optimization, and compensation
      (SOC) in case of a serious health event and thus turn into self-fulfilling
      prophecies for health and life satisfaction. Based on a longitudinal nationwide
      study with 2 measurement points over a 6-month period in 309 older people (65+
      years of age) with multiple illnesses, 2 major findings emerged: First, the
      occurrence of a serious health event predicted increased use of SOC strategies,
      which in turn predicted higher self-rated health and life satisfaction. Second,
      this effect was moderated by negative SPA, that is, in case of a serious health
      event, the perception that aging is associated with physical losses led to lower
      use of SOC strategies promoting a healthy lifestyle (B = -0.43, SE = 0.15, p <
      .01). These findings contribute to a better understanding of the underlying
      mechanisms of SPA on health by showing that negative SPA as associated with
      physical losses might impair health-related strategies that are important for
      maintaining a healthy lifestyle. Future intervention studies could attempt to
      challenge negative SPA to support effective strategy use in older adults with
      serious illnesses.

PMID- 24128076
TI  - Entity versus incremental theories predict older adults' memory performance.
AB  - The authors examined whether older adults' implicit theories regarding the
      modifiability of memory in particular (Studies 1 and 3) and abilities in general
      (Study 2) would predict memory performance. In Study 1, individual differences in
      older adults' endorsement of the "entity theory" (a belief that one's ability is
      fixed) or "incremental theory" (a belief that one's ability is malleable) of
      memory were measured using a version of the Implicit Theories Measure (Dweck,
      1999). Memory performance was assessed with a free-recall task. Results indicated
      that the higher the endorsement of the incremental theory, the better the free
      recall. In Study 2, older and younger adults' theories were measured using a more
      general version of the Implicit Theories Measure that focused on the
      modifiability of abilities in general. Again, for older adults, the higher the
      incremental endorsement, the better the free recall. Moreover, as predicted,
      implicit theories did not predict younger adults' memory performance. In Study 3,
      participants read mock news articles reporting evidence in favor of either the
      entity or incremental theory. Those in the incremental condition outperformed
      those in the entity condition on reading span and free-recall tasks. These
      effects were mediated by pretask worry such that, for those in the entity
      condition, higher worry was associated with lower performance. Taken together,
      these studies suggest that variation in entity versus incremental endorsement
      represents a key predictor of older adults' memory performance.

PMID- 24128075
TI  - A randomized study of reinforcing ambulatory exercise in older adults.
AB  - Many older adults do not meet physical activity recommendations and suffer from
      health-related complications. Reinforcement interventions can have pronounced
      effects on promoting behavior change; this study evaluated the efficacy of a
      reinforcement intervention to enhance walking in older adults. Forty-five
      sedentary adults with mild to moderate hypertension were randomized to 12-week
      interventions consisting of pedometers and guidelines to walk 10,000 steps/day or
      that same intervention with chances to win $1-$100 prizes for meeting
      recommendations. Patients walked an average of about 4,000 steps/day at baseline.
      Throughout the intervention, participants in the reinforcement intervention met
      walking goals on 82.5% +/- 25.8% of days versus 55.3% +/- 37.1% of days in the
      control condition, p < .01. Even though steps walked increased significantly in
      both groups relative to baseline, participants in the reinforcement condition
      walked an average of about 2,000 more steps/day than participants in the control
      condition, p < .02. Beneficial effects of the reinforcement condition relative to
      the control condition persisted at a 24-week follow-up evaluation, p < .02,
      although steps/day were lower than during the intervention period in both groups.
      Participants in the reinforcement intervention also evidenced greater reductions
      in blood pressure and weight over time and improvements in fitness indices, ps <
      .05. This reinforcement-based intervention substantially increased walking and
      improved clinical parameters, suggesting that larger-scale evaluations of
      reinforcement-based interventions for enhancing active lifestyles in older adults
      are warranted. Ultimately, economic analyses may reveal reinforcement
      interventions to be cost-effective, especially in high-risk populations of older
      adults.

PMID- 24128077
TI  - Withanolide-based steroids from the cultured soft coral Sinularia brassica.
AB  - Seven novel withanolides, sinubrasolides A-G (1-7), have been isolated from the
      cultured soft coral Sinularia brassica. The structures of the new metabolites
      were determined by extensive spectroscopic analyses, and the absolute
      configuration of 1 was established by X-ray crystallographic analysis. The
      cytotoxicities of compounds 1-7 against a limited panel of cancer cell lines also
      were determined. 

PMID- 24128078
TI  - Tooth loss, chewing efficiency and cognitive impairment in geriatric patients.
AB  - BACKGROUND: Patients with dementia have poorer oral health and fewer teeth than
      their peers without cognitive impairment. OBJECTIVE: The hypothesis of this study
      is that the number of natural teeth and the chewing efficiency are associated
      with cognitive functioning. METHODS: This cross-sectional study included 29
      patients diagnosed with dementia aged 75 years or older and 22 controls who were
      either cognitively normal (n = 19) or with mild cognitive impairment (n = 3).
      Neuropsychological, nutritional and dental assessments were performed. The
      chewing efficiency was evaluated with a two-colour mixing test. RESULTS: Demented
      patients and controls presented with a mean of 4.9 and 6.5 teeth, respectively
      (n.s.). The number of natural teeth was not associated with dementia (p = 0.553).
      Same results were found for age (p = 0.746) and sex (p = 0.901). The chewing
      efficiency by visual inspection proved worse in participants with dementia than
      in the controls (p < 0.011) and explained 9.3% of the variance in the diagnosis
      of dementia. Neither dental state nor chewing efficiency was related to the
      nutritional state. CONCLUSION: Chewing efficiency seems stronger associated with
      cognitive impairment than the number of teeth. Hence, in a more holistic approach
      for the geriatric assessment, the dental examination may be complemented by a
      chewing efficiency test.

PMID- 24128079
TI  - Sequencing-based gene network analysis provides a core set of gene resource for
      understanding thermal adaptation in Zhikong scallop Chlamys farreri.
AB  - Marine organisms are commonly exposed to variable environmental conditions, and
      many of them are under threat from increased sea temperatures caused by global
      climate change. Generating transcriptomic resources under different stress
      conditions are crucial for understanding molecular mechanisms underlying thermal
      adaptation. In this study, we conducted transcriptome-wide gene expression
      profiling of the scallop Chlamys farreri challenged by acute and chronic heat
      stress. Of the 13 953 unique tags, more than 850 were significantly
      differentially expressed at each time point after acute heat stress, which was
      more than the number of tags differentially expressed (320-350) under chronic
      heat stress. To obtain a systemic view of gene expression alterations during
      thermal stress, a weighted gene coexpression network was constructed. Six modules
      were identified as acute heat stress-responsive modules. Among them, four modules
      involved in apoptosis regulation, mRNA binding, mitochondrial envelope formation
      and oxidation reduction were downregulated. The remaining two modules were
      upregulated. One was enriched with chaperone and the other with microsatellite
      sequences, whose coexpression may originate from a transcription factor binding
      site. These results indicated that C. farreri triggered several cellular
      processes to acclimate to elevated temperature. No modules responded to chronic
      heat stress, suggesting that the scallops might have acclimated to elevated
      temperature within 3 days. This study represents the first sequencing-based gene
      network analysis in a nonmodel aquatic species and provides valuable gene
      resources for the study of thermal adaptation, which should assist in the
      development of heat-tolerant scallop lines for aquaculture. 

PMID- 24128081
TI  - Kinetic and thermodynamic selectivity of intermolecular C-H activation at
      [Tp'Rh(PMe3)]. How does the ancillary ligand affect the metal-carbon bond
      strength?
AB  - Tp'Rh(PMe3)(CH3)H was synthesized as a precursor to produce the coordinatively
      unsaturated fragment [Tp'Rh(PMe3)], which reacts with benzene, mesitylene, 3,3
      dimethyl-1-butene, 2-methoxy-2-methylpropane, 2-butyne, acetone, pentane,
      cyclopentane, trifluoroethane, fluoromethane, dimethyl ether, and difluoromethane
      at ambient temperature to give only one product in almost quantitative yield in
      each case. All of the complexes Tp'Rh(PMe3)(R)H were characterized by NMR
      spectroscopy, and their halogenated derivatives were fully characterized by NMR
      spectroscopy, elemental analysis, and X-ray crystallography. The active species
      [Tp'Rh(PMe3)] was also able to activate the alkynyl C-H bond of terminal alkynes
      to give activation products of the type Tp'Rh(PMe3)(C=CR)H (R = t-Bu, SiMe3,
      hexyl, CF3, Ph, p-MeOC6H4, and p-CF3C6H4). The measured relative rhodium-carbon
      bond strengths display two linear correlations with the corresponding carbon
      hydrogen bond strengths, giving a slope of 1.54 for alpha-unsubstituted
      hydrocarbons and a slope of 1.71 for substrates with alpha-substitution. Similar
      trends of energy correlations were established by DFT calculated metal-carbon
      bond strengths for the same groups of substrates. 

PMID- 24128080
TI  - Comparison of clinical examinations of back disorders and humans' evaluation of
      back pain in riding school horses.
AB  - BACKGROUND: Questionnaires are a common tool to assess people's opinion on a
      large scale or to sound them out about their subjective views. The caretakers'
      opinion about animals' "personality" has been used in many studies. The aim of
      the present study was to assess whether the owners' subjective evaluation was
      effective to detect back disorders. Back disorders have been shown to have a high
      prevalence in working horses. Caretakers from 17 riding schools (1
      caretaker/school, 161 horses) were given a questionnaire about their horses'
      health status, including back disorders. Out of these 161 horses, 59 were
      subjected to manual palpation of the spine and 102 were subjected to sEMG
      examination all along the spine. RESULTS: The results showed that subjective
      caretaker-reported evaluation via questionnaire survey was not efficient to
      detect back disorders: only 19 horses (11.8%) were reported as suffering from
      back pain, whereas the experimenters' evaluation detected 80 of them (49.7%) as
      suffering from back disorders. While most caretakers under-evaluated back
      disorders, a few "over-evaluated" it (more horses reported as affected than found
      via clinical evaluations). Horses were less prone to present back disorders when
      under the care of these "over-attentive" caretakers. CONCLUSIONS: This study
      showed that back pain is difficult to evaluate, even for professionals, and that
      subjective evaluations using a questionnaire is not valid in this case. The
      results also highlighted the real need for observational training (behaviours,
      postures) outside and during riding.

PMID- 24128082
TI  - Correlation of morphological markers of chromosomal instability in fine needle
      aspiration cytology with grade of breast cancer.
AB  - OBJECTIVE: The aim of the present study was to investigate morphological markers
      of chromosomal instability (CI) in relation to cytological grade of breast cancer
      in fine needle aspiration cytology (FNAC) specimens. METHODS: Herein we selected
      55 cases of invasive ductal carcinoma diagnosed on FNAC. Representative
      haematoxylin and eosin (H&E)-stained smears were chosen to count chromatin
      bridges, multipolar mitoses per smear, and micronuclei and nuclear budding per
      1000 carcinoma cells. The cases were also graded by two independent observers as
      grade I, II and III. The CI markers were correlated with the grade of breast
      carcinomas. RESULTS: Out of 55 carcinomas, nine were grade I, nine grade II and
      37 grade III. While none of the grade I carcinomas showed chromosomal bridges,
      the number per smear was 0.4 (+/- 0.7) and 3.1 (+/- 2.5) for grade II and III
      carcinomas, respectively. No multipolar mitoses were observed in grade I or II
      carcinomas; the number per smear was 3.7 (+/-3.0) in grade III carcinomas. The
      mean number per 1000 malignant cells of micronuclei was 1.2 (+/-1.7), 3.7 (+/
      2.1) and 12.2 (+/-5.1) and of nuclear buds was 2.3 (+/-3.2), 4.7 (+/-2.1) and
      12.4 (+/-4.7) in grade I, II and III carcinomas, respectively. There was a
      significant increase in the mean numbers of chromatin bridges, micronuclei and
      nuclear buds in grade I, II and III carcinomas (anova test; P < 0.001).
      CONCLUSION: This is the first study of four morphological markers of CI in FNAC
      smears of breast cancer. This study establishes strong correlation of these
      markers with other criteria for cytological grading.

PMID- 24128084
TI  - Identification of KIT activating mutations in paediatric solitary mastocytoma.
AB  - AIMS: Mastocytosis is an abnormal mast cell proliferation involving one or more
      organs, in particular the skin and bone marrow. In children, disease is usually
      limited to the skin, with three distinct clinical presentations: urticaria
      pigmentosa, diffuse cutaneous mastocytosis and solitary mastocytoma. Although the
      KIT D816V mutation is typically found in adult-onset mastocytosis, it is less
      commonly seen in childhood-onset mastocytosis, and the frequency of KIT mutations
      in paediatric solitary mastocytoma is poorly documented. METHODS AND RESULTS: In
      this study we analysed KIT exons 8, 9, 11, 13 and 17 in nine cases of paediatric
      solitary mastocytoma using a laboratory-developed Sanger sequencing assay. A KIT
      mutation was identified in six cases (67%), including three with the D816V
      mutation typical of adult-onset disease, and another three with an internal
      tandem duplication (p.A502_Y503dup) in exon 9, previously described in
      gastrointestinal stromal tumour. CONCLUSIONS: Paediatric solitary mastocytoma is
      frequently associated with KIT activating mutations, in keeping with a clonal
      process. KIT mutational status appears insufficient to explain the divergent
      biology of childhood and adult-onset disease.

PMID- 24128085
TI  - Self-assembly of peptide-amphiphile forming helical nanofibers and in situ
      template synthesis of uniform mesoporous single wall silica nanotubes.
AB  - A lysine based peptide amphiphile (PA) is designed and synthesized for efficient
      water immobilization. The PA with a minimum gelation concentration (MGC) of 1%
      w/v in water shows prolonged stability and can also efficiently immobilize
      aqueous mixtures of some other organic solvents. The presence of a free amine
      induced pH dependency of the gelation as the PA could form hydrogel at a pH range
      of 1-8 but failed to do so above that pH. Various spectroscopic and microscopic
      experiments such as steady state fluorescence, NMR, IR, CD, and FESEM reveal the
      presence of hydrophobic interaction, hydrogen bond, and pi-pi stacking
      interaction in the self-assembly process. The self-aggregation has been
      correlated with the design of the molecule to show the involvement of
      supramolecular forces and the hierarchical pathway. While the L analogue formed
      left-handed helical nanofibers, the other enantiomer showed opposite helicity.
      Interestingly the equimolar mixture of the isomers failed to form any fibrous
      aggregate. Although fibers formed at a subgel concentration, no helical nature
      was observed at this stage. The length and thickness of the fibers increased with
      increase in the gelator concentration. The nanofibers formed by the gelator are
      used as a template to prepare mesoporous single wall silica nanotubes (SWSNTs) in
      situ in plain water without the requirement of any organic solvent as well as any
      external hydrolyzing agent. The SWSNTs formed are open at both ends, are few
      micrometers in length, and have an average diameter of ~10 nm. The BET isotherm
      showed a type IV hysteresis loop suggesting mesoporous nature of the nanotubes.

PMID- 24128086
TI  - The validity of the diagnosis of inflammatory arthritis in a large population
      based primary care database.
AB  - BACKGROUND: Large population-based databases based on electronic medical records
      (EMRs) of patients in primary care are a useful data source to investigate
      morbidity and health care utilization. Diagnoses recorded in EMRs are doctor
      defined, but their validity can be disputed. In this study we investigated the
      validity of the diagnosis inflammatory arthritis (IA), a group of chronic
      rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis and
      ankylosing spondylitis, in primary care based EMRs. METHODS: In five general
      practices, participating in the Netherlands Information Network of General
      Practice (LINH), EMRs of 219 patients with a diagnostic code of IA were
      systematically reviewed on characteristics which are not routinely extracted for
      the LINH database. The diagnosis IA was confirmed when we found, based on a
      correspondence with a medical specialist, the following diagnoses in the free
      text fields of the EMR: oligoarthritis, polyarthritis, rheumatoid arthritis
      and/or spondyloarthropathy. These results were used to determine the validity of
      the diagnosis IA in EMRs and to develop an algorithm to improve diagnostic
      validity. RESULTS: From the 219 patients diagnosed as IA in the database, the
      diagnosis IA was confirmed in 155 patients (70.8%). The algorithm, which resulted
      in a group of patients with as many as possible confirmed IA-diagnosed patients
      without excluding too many patients from our dataset, was when patients fulfilled
      at least one of the following three criteria: 1) a repeat prescription for a
      disease-modifying antirheumatic drug (DMARD) and/or biological agent, 2) >= four
      contacts or one episode with a diagnostic code for IA, combined with at least two
      IA-related prescriptions (excluding DMARDs/biological agents), and 3) age at
      diagnosis >= 61 years. After applying this algorithm, the percentage of correctly
      diagnosed IA patients increased from 71% to 78% reducing the size of our study
      population by 36%. CONCLUSIONS: Based on additional diagnostic information, the
      diagnosis IA from EMRs of patients in primary care is sufficiently valid when
      using the proposed algorithm. After applying the algorithm, the percentage of
      correctly diagnosed IA patients increased from 71% to 78%.

PMID- 24128088
TI  - Evaluation of effects of multiple candidate genes (LEP, LEPR, MC4R, PIK3C3, and
      VRTN) on production traits in Duroc pigs.
AB  - We evaluated multiple effects of genetic variations of five candidate loci (LEP,
      LEPR, MC4R, PIK3C3 and VRTN) on four production traits (average daily weight gain
      (ADG); backfat thickness (BFT); loin eye muscle area (EMA); and intramuscular fat
      content (IMF)) in a closed nucleus herd of pure Duroc pigs. Polymorphisms in
      LEPR, MC4R and PIK3C3 had significant single gene effects on ADG and BFT. The
      additive genetic variance in ADG and BFT (16.99% and 22.51%, respectively) was
      explained by genetic effects of these three loci. No correlations were observed
      between the LEP genotype and production traits in this study. Although we
      detected marginally epistatic interactions between LEPR and PIK3C3 on the eye
      muscle area, there were no significant epistatic effects on any traits among all
      loci pairs. These results suggest that LEPR, MC4R, PIK3C3 and VRTN may
      independently influence growth rate and fat deposition. Furthermore, the
      statistical models for predicting the breeding values of each trait had the
      lowest Akaike's information criterion values when considering the effect of the
      MC4R, LEPR, PIK3C3 and VRTN genotype simultaneously. These results suggest that
      LEPR, MC4R, PIK3C3 and VRTN are useful markers for accurately predicting breeding
      values in Duroc pigs. 

PMID- 24128089
TI  - A review on novel vesicular drug delivery: proniosomes.
AB  - Nanotechnology has brought a revolution in the field of science, which has
      subsequently lead to development of novel dosage forms such as niosomes,
      liposomes and proniosomes. Proniosomes overcome the demerits involved with
      niosomal and liposomal drug delivery systems. Proniosomes are liquid crystalline
      compact niosome hybrids which upon hydration form niosomes. They help in reducing
      physical stability problems involved with niosomes such as leaking, fusion,
      aggregation and provide convenience in dosing, distribution, transportation and
      storage showing improved results than conventional niosomes. This review focuses
      on different aspects of proniosome such as preparation, characterization, drug
      release, applications, merits, demerits, present scenario in market and future
      trends.

PMID- 24128087
TI  - Metabolic control of the epigenome in systemic Lupus erythematosus.
AB  - Epigenetic mechanisms are proposed to underlie aberrant gene expression in
      systemic lupus erythematosus (SLE) that results in dysregulation of the immune
      system and loss of tolerance. Modifications of DNA and histones require
      substrates derived from diet and intermediary metabolism. DNA and histone
      methyltransferases depend on S-adenosylmethionine (SAM) as a methyl donor. SAM is
      generated from adenosine triphosphate (ATP) and methionine by methionine
      adenosyltransferase (MAT), a redox-sensitive enzyme in the SAM cycle. The
      availability of B vitamins and methionine regulate SAM generation. The DNA of SLE
      patients is hypomethylated, indicating dysfunction in the SAM cycle and
      methyltransferase activity. Acetyl-CoA, which is necessary for histone
      acetylation, is generated from citrate produced in mitochondria. Mitochondria are
      also responsible for de novo synthesis of flavin adenine dinucleotide (FAD) for
      histone demethylation. Mitochondrial oxidative phosphorylation is the dominant
      source of ATP. The depletion of ATP in lupus T cells may affect MAT activity as
      well as adenosine monophosphate (AMP) activated protein kinase (AMPK), which
      phosphorylates histones and inhibits mechanistic target of rapamycin (mTOR). In
      turn, mTOR can modify epigenetic pathways including methylation, demethylation,
      and histone phosphorylation and mediates enhanced T-cell activation in SLE.
      Beyond their role in metabolism, mitochondria are the main source of reactive
      oxygen intermediates (ROI), which activate mTOR and regulate the activity of
      histone and DNA modifying enzymes. In this review we will focus on the sources of
      metabolites required for epigenetic regulation and how the flux of the underlying
      metabolic pathways affects gene expression.

PMID- 24128090
TI  - Assessing the causal effect of organ transplantation on the distribution of
      residual lifetime.
AB  - Because the number of patients waiting for organ transplants exceeds the number
      of organs available, a better understanding of how transplantation affects the
      distribution of residual lifetime is needed to improve organ allocation. However,
      there has been little work to assess the survival benefit of transplantation from
      a causal perspective. Previous methods developed to estimate the causal effects
      of treatment in the presence of time-varying confounders have assumed that
      treatment assignment was independent across patients, which is not true for organ
      transplantation. We develop a version of G-estimation that accounts for the fact
      that treatment assignment is not independent across individuals to estimate the
      parameters of a structural nested failure time model. We derive the asymptotic
      properties of our estimator and confirm through simulation studies that our
      method leads to valid inference of the effect of transplantation on the
      distribution of residual lifetime. We demonstrate our method on the survival
      benefit of lung transplantation using data from the United Network for Organ
      Sharing. 

PMID- 24128091
TI  - Tropical marginal seas: priority regions for managing marine biodiversity and
      ecosystem function.
AB  - Tropical marginal seas (TMSs) are natural subregions of tropical oceans
      containing biodiverse ecosystems with conspicuous, valued, and vulnerable
      biodiversity assets. They are focal points for global marine conservation because
      they occur in regions where human populations are rapidly expanding. Our review
      of 11 TMSs focuses on three key ecosystems-coral reefs and emergent atolls, deep
      benthic systems, and pelagic biomes-and synthesizes, illustrates, and contrasts
      knowledge of biodiversity, ecosystem function, interaction between adjacent
      habitats, and anthropogenic pressures. TMSs vary in the extent that they have
      been subject to human influence-from the nearly pristine Coral Sea to the heavily
      exploited South China and Caribbean Seas-but we predict that they will all be
      similarly complex to manage because most span multiple national jurisdictions. We
      conclude that developing a structured process to identify ecologically and
      biologically significant areas that uses a set of globally agreed criteria is a
      tractable first step toward effective multinational and transboundary ecosystem
      management of TMSs. 

PMID- 24128092
TI  - Residues flanking scissile bonds in Factor VIII modulate rates of cleavage and
      proteolytic activation catalyzed by Factor Xa.
AB  - Factor Xa (FXa) proteolytically activates Factor VIII (FVIII) by cleaving P1
      residues Arg(372), Arg(740), and Arg(1689). The Arg(372) site represents the rate
      limiting step for procofactor activation, whereas cleavage at Arg(740) is a fast
      step. FXa also catalyzes inactivating cleavages that occur on a slower time scale
      than the activating ones. To assess the role of sequences flanking the Arg(372)
      and Arg(740) sites, recombinant FVIII variants in which P3-P3' sequences were
      swapped individually or in combination were prepared. Replacing the Arg(372)
      flanking sequence with that from the Arg(740) site increased the rate of cleavage
      at Arg(372), as judged by the ~5-fold increased rate in A1 subunit generation,
      and reduced the FVIIIa-dependent lag time for in situ FXa generation. The
      reciprocal swap yielded a nearly 2-fold increase in the rate of Arg(372)
      cleavage, while the combined double-swap variant showed a 10-fold rate increase
      at that site, consistent with the individual effects being additive. Although
      this cleavage represents the slow step for activation, the rate of this reaction
      appeared to be ~9-fold greater than the rate of the primary inactivating cleavage
      at Arg(336) in generating the A1(336) product. Interestingly, replacement of the
      Arg(372) flanking sequence with the Arg(740) sequence combined with an
      Arg(740)Gln mutation yielded both more rapid cleavage of the Arg(372) site and
      accelerated inactivating cleavages within the A1 subunit. These results indicate
      that flanking sequences in part modulate the reaction rates required for
      procofactor activation and influence the capacity of FXa as an initial activator
      of FVIII rather than an inactivator.

PMID- 24128093
TI  - Environmentally benign synthesis of indeno[1,2-b]quinolines via an intramolecular
      Povarov reaction.
AB  - A new synthetic route to indeno[1,2-b]quinolines via reactions of o
      propargylbenzaldehydes with N-aryl amines based on an intramolecular aza-Diels
      Alder (Povarov) reaction has been developed. This method offers several
      advantages such as no requirement for an oxidant, high efficiency, and a wide
      reaction scope. 

PMID- 24128094
TI  - [Co-payment and the hospital pharmacy].

PMID- 24128095
TI  - [Challenges and opportunities of aging and chronicity for the hospital
      pharmacist].

PMID- 24128096
TI  - [Infectious events during the first year of treatment with an antagonist of the
      tumor necrosis factor].
AB  - OBJECTIVE: To assess the incidence of severe infections in patients treated with
      anti-TNF-??drugs, during the first year of treatment with these drugs. MATERIALS
      AND METHOD: Retrospective observational study carried out at a general hospital
      from a sample of patients receiving their first anti-TNF-??drug, according to
      approved indications, to treat a rheumatic disease. Each patient follow-up lasted
      for 2 years: the year before receiving the drug and the year after starting on
      this therapy. We considered those severe infectious events requiring hospital
      admission. A cohort study was performed before-after. The incidence rates of
      number of events (infections) per 100,000 inhabitants/year for the first
      treatment year and the previous year (control period) were calculated. The
      relative risk was calculated. RESULTS: We included 196 patients. Twelve severe
      infectious events were recorded during the first treatment year, with a relative
      risk of 2.4. The biological drug most frequently associated to infection was
      Adalimumab. All patients having an infection had been previously or concomitantly
      treated with Methotrexate, and 90.6% with glucocorticosteroids. The main location
      of the infection was the respiratory system (58.3%), and the gram-positive
      microorganisms were the most frequent (58.3%). CONCLUSIONS: The use of anti-TNF
      ??drugs, and mainly Adalimumab, represents a risk factor for suffering severe
      infections, mainly at the respiratory tract, produced by gram-positive
      microorganisms. The use of immunosuppressive drugs such as Methotrexate and
      glucocorticosteroids seems to increase the risk for such events.

PMID- 24128097
TI  - [Efficiency of initiation with ambrisentan versus bosentan in the treatment of
      pulmonary arterial hypertension].
AB  - OBJECTIVE: To evaluate the efficiency of initiation with endothelin receptor
      antagonists, ambrisentan or bosentan, followed by sequential combination with
      phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary
      arterial hypertension, from the Spanish National Health System perspective.
      METHODS: A Markov model was developed based on the four New York Heart
      Association functional classes. A panel of three experts reached a consensus on
      patient management based on clinical practice. Patients revised their treatment
      every 12 weeks, based on their health status and previous medication records.
      Pharmacological treatment costs and costs associated with very frequent adverse
      events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in
      qualityadjusted life years (QALY). A probabilistic sensitivity analysis was
      performed. RESULTS: No clinically relevant differences in QALY per-patient and
      year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902,
      respectively. Initiation with ambrisentan resulted in lower pharmacological
      treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In
      the sensitivity analysis, initiation with ambrisentan resulted in a negative
      significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no
      significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101].
      CONCLUSIONS: Initiation with ambrisentan followed by sequential combination with
      phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at
      lower costs than initiation with bosentan.

PMID- 24128098
TI  - [Quantitative analysis of drug expenditures variability in dermatology units].
AB  - BACKGROUND: Variability in adjusted drug expenditures among clinical departments
      raises the possibility of difficult access to certain therapies at the time that
      avoidable expenditures may also exist. Nevertheless, drug expenditures are not
      usually applied to clinical practice variability analysis. AIMS: To identify and
      quantify variability in drug expenditures in comparable dermatology department of
      the Servicio Andaluz de Salud. METHODS: Comparative economic analysis regarding
      the drug expenditures adjusted to population and health care production in 18
      dermatology departments of the Servicio Andaluz de Salud. The 2012 cost and
      production data (homogeneous production units -HPU-)were provided by Inforcoan,
      the cost accounting information system of the Servicio Andaluz de Salud. RESULTS:
      The observed drug expenditure ratio ranged from 0.97?/inh to 8.90?/inh and from
      208.45?/HPU to 1,471.95?/ HPU. The Pearson correlation between drug expenditure
      and population was 0.25 and 0.35 for the correlation between expenditure and
      homogeneous production (p=0.32 and p=0,15, respectively), both Pearson
      coefficients confirming the lack of correlation and arelevant degree of
      variability in drug expenditures. CONCLUSION: The quantitative analysis of
      variability performed through Pearson correlation has confirmed the existence of
      drug expenditure variability among comparable dermatology departments.

PMID- 24128099
TI  - [Prescription analysis of continuous home care oxygen therapy after intervention
      pharmaceutical].
AB  - OBJECTIVES: Analyze developments in the clinical adequacy of prescribing
      continuous home oxygen therapy to current regulations in the Andalusian Health
      Service. METHODOLOGY: Were reviewed in a previous study requirements and
      continuing new domiciliary oxygen therapy conducted from January 2008 to December
      2009. It constituted a Monitoring Committee Multidisciplinary and turned to
      analyzing the appropriateness of prescribing after two pharmaceutical
      interventions from April 2011 to March 2012. Statistical analysis was performed
      by SPSS 15.0 for Windows, the dependent variable being the correct blade
      adjustment to the first prescription and then, and as independent prescribing
      different units. In cases in which the prescribing correct sheet, variables were
      analyzed mandatory. RESULTS: 163 prescriptions were checked manually with a rate
      of compliance with the regulations of 66.30%, slightly higher than the results of
      the previous study (55.72% in 2008, 47.70% in 2009). The intervention did not
      achieve a greater degree the outlook for lack of financial and material
      resources, affecting one of the fundamental objectives were patient reviews.
      CONCLUSIONS: Pharmaceutical intervention has ensured that the prescription
      conforms to the rules and perform better, but has not been able to control the
      issue of revisions to rely on other medical and administrative units requesting
      increased technological and human resources to facilitate control.

PMID- 24128100
TI  - [Potential drug interactions in patients with sepsis admitted to the intensive
      care unit].
AB  - OBJECTIVE: To analyze, detect and classify potential drug interactions in
      patients with sepsis admitted to the intensive care unit. METHODS: This
      prospective observational cohort study of septic patients was conducted between
      April 2010 and August 2011. Data collection included demographic characteristics,
      clinical features, and analysis of pharmacotherapy. RESULTS: Of 86 patients, 80%
      had potential drug interactions, with a mean of 1.84 +/- 1.09 interaction per
      patient. Regarding the classification of drug interactions, 64.2% had a
      pharmacodynamic profile, 60% were of major severity, 53.3% had a rapid onset of
      action, and 53.8% had good documentation. The prevalence of interactions was
      associated with age, number of drugs prescribed, and length of stay in the
      intensive care unit (p < 0.001). CONCLUSION: This study showed that drug
      interactions represent an important clinical concern in septic patients admitted
      to intensive care units.

PMID- 24128101
TI  - Assessment of new drugs in a tertiary hospital using a standardized tool.
AB  - OBJECTIVE: To describe the profile of new drugs evaluated by the Pharmacy and
      Therapeutics committee in a tertiary hospital using a standardized tool, the
      Guideline for the Introduction of New Drugs in the Formulary (GINF form), as main
      objective. MATERIALS AND METHODS: Retrospective observational study of drugs was
      assessed during 2008-2011. Variables related to the drug, the request, and the
      result of the evaluation were collected based on information contained in the
      GINF form and in the assessment reports. RESULTS: 63 of 75 assessed drugs (84%)
      were included in the hospital formulary. Only one drug (1%) was included without
      any restrictions. The rest of them were included as therapeutic equivalents (23%)
      or under specific recommendations (61%). Half of the drugs (6) not included had
      insufficient evidence of effectiveness compared with current treatments.
      Haematology and Medical Oncology were found to be the most active medical
      services in the application process. There was a high prevalence of drugs that
      had more than one advanced clinical trial (phase III and/or phase IV).
      Furthermore, 28% of assessed drugs were associated with a financial burden of
      more than ?10,000 per year for our hospital. Highquality information was provided
      by applicants to the P&T committee for drugs that were finally included. However,
      the relationship between the information provided to the P&T committee and its
      decision was not statistical significance. CONCLUSION: The requests received were
      primarily related to drugs intended for parenteral use and most of them were
      antineoplastic drugs. The medical departments most heavily represented were
      Haematology and Oncology.

PMID- 24128102
TI  - [Assessment of the utilization of angiotensin receptor blockers in hypertension].
AB  - OBJECTIVE: To assess the degree in which the utilization of angiotensin receptor
      blockers (ARBs) in our Healthcare Area fits the criteria proposed by the
      Autonomous Community of Madrid (CAM) before setting "Plan de Actuacion de ARA-II"
      ("Action Plan ARA-II"). To study the indications for which are prescribed and to
      identify those factors that can show influence in prescription. METHODS: Drug
      utilization study of the type indication-prescription, descriptive and
      transversal, for which ARBs-treated and hypertensive patients admitted to a
      University General Hospital for a study period of 3 months were selected. Based
      on the clinical situations summarized in the CAM Document "Criterios para
      establecer el lugar en la terapeutica de los antagonistas de los receptores de la
      angiotensina II" ("Criteria for the place of angiotensin receptor blockers in the
      therapeutic"), a percentage of patients with "appropriate prescription" and
      "inadequate prescription" of ARBs was calculated and analyzed in order to
      determine if the age and the sex were related to the type of prescription or the
      main indications for which they had been prescribed. RESULTS: Out of the 153
      patients included in the study, 67.3% had a "inadequate prescription", 47.6% of
      them due to an ARBs prescription as the first drug inhibitor of the
      reninangiotensin- aldosterone system and 34.0% owing to a poor control of blood
      pressure with angiotensin-converting enzyme inhibitors (ACEi). There were no
      statistically significant differences found either by age or sex in the type of
      prescription or in the main indications for which they were prescribed.
      CONCLUSIONS: The adequacy of the criteria for the utilisation of ARBs Document
      occurred in 32.7% of cases. In addition, factors such as age and sex did not seem
      to affect the type of prescription. Misconceptions of superiority of ARBs versus
      ACEi were evidenced as well.

PMID- 24128104
TI  - [Visa at a tertiary hospital].
AB  - OBJECTIVE: To analyze the visa application process and his activity at a tertiary
      hosipital. MATERIAL AND METHODS: Descriptive study of the drug s visa activity
      during the period April 2011-April 2012. We designed a database and defined
      categories on the study variables: patients and recipes. For patients admitted to
      the Visa Unit, issues detected were recorded based on a previously established
      classification. RESULTS: 6738 patients were included. They involved the visa of
      8,465 recipes. The visa was applied to 170 drugs and nutrition products
      different, being the majority Tacrolimus. During this period, we detected a total
      of 420 incidents being the most frequent "No clinical document" (46.67%) and the
      "Formal completion errors" (28.57%). CONCLUSIONS: This work has allowed a more
      detailed analysis of the activity, the types of incidents and the identification
      of areas for improvement.

PMID- 24128103
TI  - [Retrospective analysis of omalizumab in patients with severe allergic asthma].
AB  - OBJECTIVE: To assess the efficacy and safety profile of omalizumab treatment. The
      conditions under which omalizumab was prescribed agreed with those in Xolair(r)
      drug information: age > 12 years old, severe uncontrolled asthma, FEV1 < 80%, IgE
      30-700 UI/ml and positive test results for perennial allergens. METHODS:
      Asthmatic patients treated with omalizumab between January 2010 and July 2011
      were evaluated retrospectively. Age, sex, weight, IgE level, concomitant asthma
      medications, change in FEV1, emergency department visits, hospitalizations,
      asthma exacerbations and corticosteroids bursts were recorded before and after
      omalizumab initiation. A 1.5- year period was chosen. RESULTS: A total of 22
      patients were included. The mean weight of subjects was 73 Kg (range, 51-102).
      Mean IgE was 203 UI/ml (range, 30-992) and mean FEV1 60% (range, 30-93%) at
      baseline. Adverse events were observed in 4 patients. There were no significant
      changes in FEV1 values after omalizumab treatment but omalizumab was associated
      with a reduction in concomitant asthma medications use in 14 patients and
      improvements in global asthma control in 12. CONCLUSION: In these patients add-on
      therapy with omalizumab reduced asthma exacerbations and emergency visits or
      hospitalizations. Only 55% of patients significantly improved global asthma
      control and no significant changes in FEV1 were observed.

PMID- 24128105
TI  - [Review of enteral drugs administration for viral diseases: HIV, HBV and HCV].
AB  - INTRODUCTION: Patients infected with HIV demographic have changed in recent years
      and sometimes, co-infections with hepatitis virus B and C are common. Due to
      their longer survival, these patients often present diseases or undergo surgical
      procedures that preclude the intake of drugs, requiring the use of the enteral
      administration. This practice, however, may fail due to the lack of adherence,
      unsuitable drug blood concentrations caused by malabsorption or interactions, and
      dosage errors. We aim to develop management guidelines for antiviral drugs
      enteral administration. MATERIAL AND METHODS: We reviewed the technical
      specifications of drugs used in HIV, HBV or HCV. A search was conducted in
      Pubmed(r) database and Micromedex(r), manufacturers were contacted for futher
      information and other related literature was reviewed. RESULTS: The results are
      shown in table 1. DISCUSSION: Although in pharmaceutical practice crushing
      tablets is common, sometimes suspension of crushed drugs in water is not
      completely appropriate for enteral administration, because this practice may
      alter the bioavailability of drugs, which may modify the therapeutic effect.
      There is currently not enough evidence that supports the practice of crushed and
      suspension of drugs exposed in this study. Therefore, the bioavailability of
      different formulations should be studied more carefully, especially of recent
      marketing drugs.

PMID- 24128106
TI  - [Eltrombopag for the treatment of thrombocytopenia in patients with chronic
      hepatitis C: two case reports].

PMID- 24128108
TI  - [McHutchison's legacy and adherence in hepatitis C].

PMID- 24128107
TI  - [Toxicodermia by bendamustine: development of a desensization protocol].

PMID- 24128109
TI  - [Arterial occlusion associated with interaction between ritonavir and ergotamine
      in HIV patient].

PMID- 24128111
TI  - Graphene--the mother of two-dimensional (2-D) materials.

PMID- 24128110
TI  - [Ponatinib: new option for the treatment of resistant chronic myeloid leukemia].

PMID- 24128112
TI  - Synthesis of Ex(n)Box cyclophanes.
AB  - A rapid and efficient synthesis of the extended bipyridinium-based class of
      cyclophanes--that is, Ex(n)Box(4+) (n = 0-3), where n is the number of p
      phenylene rings inserted between the pyridinium rings--is demonstrated, resulting
      in much higher yields of products along with a reduced output of oligomeric
      byproducts. Although each cyclophane can be synthesized readily without the use
      of a precise stoichiometric amount of template, ExBox(4+) can be prepared in 66%
      yield (following crystallization) using six equivalents of pyrene in a template
      directed protocol. This new methodology has been employed to synthesize, in
      modest yield, a nearly 2.5 nm long cyclophane consisting of 12 aromatic rings.

PMID- 24128113
TI  - Maternal breastfeeding self-efficacy and the breastfeeding behaviors of newborns
      in the practice of exclusive breastfeeding.
AB  - OBJECTIVES: To explore the maternal breastfeeding self-efficacy of Chinese women,
      the breastfeeding behaviors of newborns, and the relationship with breastfeeding
      outcomes at 6 weeks postpartum. DESIGN: Descriptive correlation study. SETTING:
      Postnatal ward of a regional maternity hospital PARTICIPANTS: All postnatal
      Chinese women who were admitted from mid-February 2010 to mid-March 2010 with the
      intention of breastfeeding. METHODS: The Infant Breastfeeding Assessment Tool
      (IBFAT) was used to assess neonatal breastfeeding behaviors, and a modified
      Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form (MBSES-SF)
      was used to examine the breastfeeding self-efficacy of mothers. RESULTS: A total
      of 199 postnatal women were recruited. At 6 weeks postpartum, 85 (42.7%) infants
      were bottle-fed, 66 (33.2%) were complementary breastfed, and 48 (24.1%) were
      exclusively breastfed. The significant contributing factors for exclusive
      breastfeeding were women who planned to breastfeed for at least 6 months (odds
      ratio [OR] = 5.537, 95% confidence interval [CI] [2.430, 12.619], p <= 0.001),
      women with a high level of breastfeeding self-efficacy (OR =, 7.776, 95% CI
      [2.546, 23.748], p <= 0.001), and those women whose infants had high-IBFAT scores
      (OR = 2.381, 95% CI [1.019, 5.562], p = .045). CONCLUSIONS: Maternal
      breastfeeding confidence and newborn breastfeeding behavior are strong predictors
      of breastfeeding duration as well as exclusivity. Health care professionals
      should monitor the breastfeeding behavior of newborns and not only provide
      mothers with the factual information on breastfeeding but help also them to
      develop maternal confidence in breastfeeding before they are discharged.

PMID- 24128115
TI  - Meroterpenoids with diverse ring systems from the sponge-associated fungus
      Alternaria sp. JJY-32.
AB  - Fifteen meroterpenoids (1-15) with diverse ring systems including an
      unprecedented oxaspiro[5.5]nonane-fused cyclohexenone (1), hydrogenated
      benzofurans (2-5), hydrogenated chromans (6, 7), hydrogenated
      cyclopenta[b]chromans (8-11), and four monocyclic structures (12-15) were
      isolated from the sponge-associated fungus Alternaria sp. JJY-32. The structures
      were elucidated by detailed spectroscopic analysis, including 2D NMR and
      electronic circular dichroism (ECD) calculations, and assisted by chemical
      derivatizations. On the basis of supplementation experiments with specific enzyme
      inhibitors and putative precursors, a shikimate-isoprenoid hybrid biosynthetic
      pathway is proposed. The NF-kappaB inhibitory activities of 1-15 were tested, and
      all of them, except 6 and 7 (IC50 > 100 MUM), showed activities with IC50 values
      ranging from 39 to 85 MUM in RAW264.7 cells.

PMID- 24128116
TI  - Continuous flow analysis method for determination of dissolved reactive
      phosphorus in ice cores.
AB  - Phosphorus (P) is an essential macronutrient for all living organisms. Phosphorus
      is often present in nature as the soluble phosphate ion PO4(3-) and has
      biological, terrestrial, and marine emission sources. Thus PO4(3-) detected in
      ice cores has the potential to be an important tracer for biological activity in
      the past. In this study a continuous and highly sensitive absorption method for
      detection of dissolved reactive phosphorus (DRP) in ice cores has been developed
      using a molybdate reagent and a 2-m liquid waveguide capillary cell (LWCC). DRP
      is the soluble form of the nutrient phosphorus, which reacts with molybdate. The
      method was optimized to meet the low concentrations of DRP in Greenland ice, with
      a depth resolution of approximately 2 cm and an analytical uncertainty of 1.1 nM
      (0.1 ppb) PO4(3-). The method has been applied to segments of a shallow firn core
      from Northeast Greenland, indicating a mean concentration level of 2.74 nM (0.26
      ppb) PO4(3-) for the period 1930-2005 with a standard deviation of 1.37 nM (0.13
      ppb) PO4(3-) and values reaching as high as 10.52 nM (1 ppb) PO4(3-). Similar
      levels were detected for the period 1771-1823. Based on impurity abundances, dust
      and biogenic particles were found to be the most likely sources of DRP deposited
      in Northeast Greenland. 

PMID- 24128114
TI  - Comparative transcriptional analysis of three human ligaments with distinct
      biomechanical properties.
AB  - One major aim of regenerative medicine targeting the musculoskeletal system is to
      provide complementary and/or alternative therapeutic approaches to current
      surgical therapies, often involving the removal and prosthetic substitution of
      damaged tissues such as ligaments. For these approaches to be successful,
      detailed information regarding the cellular and molecular composition of
      different musculoskeletal tissues is required. Ligaments have often been
      considered homogeneous tissues with common biomechanical properties. However,
      advances in tissue engineering research have highlighted the functional relevance
      of the organisational and compositional differences between ligament types,
      especially in those with higher risks of injury. The aim of this study was to
      provide information concerning the relative expression levels of a subset of key
      genes (including extracellular matrix components, transcription factors and
      growth factors) that confer functional identity to ligaments. We compared the
      transcriptomes of three representative human ligaments subjected to different
      biomechanical demands: the anterior cruciate ligament (ACL); the ligamentum teres
      of the hip (LT); and the iliofemoral ligament (IL). We revealed significant
      differences in the expression of type I collagen, elastin, fibromodulin,
      biglycan, transforming growth factor beta1, transforming growth interacting
      factor 1, hypoxia-inducible factor 1-alpha and transforming growth factor beta
      induced gene between the IL and the other two ligaments. Thus, considerable
      molecular heterogeneity can exist between anatomically distinct ligaments with
      differing biomechanical demands. However, the LT and ACL were found to show
      remarkable molecular homology, suggesting common functional properties. This
      finding provides experimental support for the proposed role of the LT as a hip
      joint stabiliser in humans. 

PMID- 24128117
TI  - A new minor homoisoflavonoid from Caesalpinia sappan.
AB  - Homoisoflavonoid is a special type of flavonoid with the perspectives of both
      chemical diversity and significant biological activities. During our ongoing
      studies on the discovery of novel homoisoflavonoids from traditional Chinese
      medicines, a new minor 3,4-di-O-substituted homoisoflavonoid, 3',4-di-O
      methylepisappanol (1), was isolated from Caesalpinia sappan, and its structure
      was determined to be (3R,4R)-3,7-dihydroxy-3-(3'-methoxy-4'-hydroxybenzyl)-4
      methoxychroman by various spectroscopic analyses. Meanwhile, a known xanthone
      derivate, 2-methoxy-3-hydroxyxanthone (2) was also isolated, which is the first
      example from the genus Caesalpinia. 

PMID- 24128119
TI  - Two-role model of an interaction network of free-living gamma-proteobacteria from
      an oligotrophic environment.
AB  - Antagonistic interactions are frequently observed among bacteria in the
      environment and result in complex networks, which could promote co-existence, and
      therefore promote biodiversity. We analysed interactions of aquatic bacteria
      isolated by their ability to grow in Pseudomonas isolation agar from Churince,
      Cuatro Cienegas, Mexico. In the resulting network, highly antagonistic and highly
      sensitive strains could be distinguished, forming a largely hierarchical
      structure. Most of the highly antagonistic strains belonged to the genus
      Pseudomonas. The network was sender-determined, which means that the antagonist
      strains had a larger influence on its structure than the sensitive ones. Very few
      interactions were necessary to connect all strains, implying that the network was
      'small world'. The network was highly nested, having a core of highly interacting
      strains, with which the less antagonistic or highly sensitive interact. A
      probabilistic model was built, which captured most features of the network.
      Biological interpretation of the model implied a state in which many different
      antagonistic mechanisms were present, and most strains were resistant to them.
      Our work shows that strains of Pseudomonas from the water column at Cuatro
      Cienegas have the potential to interact antagonistically with many closely
      related strains and that these interactions are usually not reciprocal. 

PMID- 24128118
TI  - Utility of the REBA MTB-Rifa(r) assay for rapid detection of rifampicin resistant
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Drug-resistant tuberculosis (TB), including resistance to both
      rifampicin (RIF) and isoniazid (INH) referred to as multidrug-resistant
      tuberculosis (MDR-TB), has become an increasing global threat in recent years.
      Effective management of patients infected with MDR-TB strains requires
      identifying such patients by performing conventional drug-susceptibility testing
      (DST) on bacteria isolated from sputum, a process that can take up to 2 months.
      This delay in diagnosis can result in worsening and continued transmission of MDR
      TB. Molecular methods that rely upon nucleic acid amplification of specific
      alleles known to be associated with resistance to specific drugs have been
      helpful in shortening the time to detect drug resistant TB. METHODS: We
      investigated the utility of the REBA MTB-Rifa(r), a commercially available line
      probe assay (LPA) for detecting rifampicin (RIF) resistance in the RIF resistance
      determining region (RRDR) of the rpoB gene. Altogether, 492 Mycobacterium
      tuberculosis (M. tuberculosis) clinical isolates and additional 228 smear- and
      culture-positive sputum samples with confirmed M. tuberculosis were collected
      from subjects with suspected MDR-TB in South Korea. The results were compared
      with conventional phenotypic DST and sequencing of the rpoB gene. RESULTS: A
      total of 215 of the 492 isolates were resistant to RIF by conventional DST, and
      of which 92.1% (198/215) were MDR-TB strains. The REBA MTB-Rifa(r) assay
      identified RIF resistance in 98.1% (211/215) of these isolates but failed to
      identify resistance in four phenotypically RIF resistant isolates. These four
      isolates lacked mutations in the RRDR but three were confirmed to be MDR-TB
      strains by sequencing. The sensitivity and specificity of this test for clinical
      isolates was thus 98.1% (211/215) and 100% (277/277), respectively. When applied
      directly to 228 smear positive sputum samples, the sensitivity and the
      specificity of REBA MTB-Rifa(r) assay was 100% (96/96, 132/132), respectively.
      CONCLUSIONS: These findings support the use of the REBA MTB-Rifa(r) assay for
      rapid detection of RIF resistance on clinical isolates and smear positive sputum
      samples. The results also suggest that RIF resistance is a good surrogate marker
      of MDR-TB in South Korea and the need to add more probes to other LPAs which can
      cover newly identified mutations relevant to RIF resistance.

PMID- 24128120
TI  - The association between three promoter polymorphisms of IL-10 and inflammatory
      bowel diseases (IBD): a meta-analysis.
AB  - AIM: To assess the relationship of the Interleukin-10 (IL-10) -1082G/A
      (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) polymorphism with
      inflammatory bowel disease (IBD) by means of meta-analysis. METHODS: Published
      data addressing the association between polymorphism of the IL-10 with Crohn's
      disease (CD) and Ulcerative colitis (UC) were selected from electronic databases.
      A total of 17 studies including 4132 cases and 5109 controls were included in
      this meta-analysis which detected whether -1082G/A, -819C/T and -592C/A
      polymorphism were associated with CD or UC susceptibility. RESULT: The IL-10 
      819C/T and -519C/A variant allele observed a significant association with UC (OR
      1.16, 95%CI 1.03-1.31 and OR 1.19, 95%CI 1.03-1.38) not CD while there is no
      significant association between -1082G/A and UC or CD. CONCLUSION: The IL-10 
      819C/T and -592C/A polymorphisms contribute to susceptibility to UC, but IL-10 
      1082G/A polymorphism neither associated with CD nor UC.

PMID- 24128121
TI  - The influence of borderline personality features on inpatient adolescent suicide
      risk.
AB  - Suicide is a leading cause of death among adolescents and suicidal behavior is
      one of the primary risk factors for youth psychiatric hospitalizations. A number
      of studies indicate that depression and substance abuse are associated with
      suicide risk in this population, but less is known about the role of borderline
      personality features or their incremental influence over other known risk factors
      in indicating suicidal behavior among adolescents. This study examined whether
      borderline features were associated with suicide risk when controlling for
      symptoms of depression and substance abuse in a sample of adolescents
      hospitalized in an inpatient psychiatric facility. Self-report data from 477
      adolescent psychiatric inpatients were used to test hypotheses about the
      association of borderline features with suicide risk after controlling for other
      common risk factors. Borderline features were significantly related to suicide
      risk even after accounting for symptoms of depression and substance abuse. These
      findings underscore the clinical value of routinely assessing borderline features
      among adolescents.

PMID- 24128122
TI  - Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for
      brain targeting.
AB  - The central nervous system (CNS) is an immunological privileged sanctuary site
      providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective
      in reducing plasma viral levels, cannot eradicate the virus completely from the
      body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB)
      leads to insufficient delivery. Therefore, developing a novel approaches
      enhancing the CNS delivery of anti-HIV drugs are required for the treatment of
      neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for
      enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is
      a protease inhibitor which is a poorly soluble drug widely used as antiretroviral
      drug, with oral bioavailability is about 4%. The spontaneous emulsification
      method was used to prepare drug-loaded o/w nanoemulsion, which was characterized
      by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation
      studies were performed using sheep nasal mucosa. The optimized NE showed a
      significant increase in drug permeation rate compared to the plain drug
      suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no
      significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution
      studies show higher drug concentration in brain after intranasal administration
      of NE than intravenous delivered PDS. The higher percentage of drug targeting
      efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for
      optimized NE indicated effective CNS targeting of SQVM via intranasal route.
      Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport
      of drug in the CNS at larger extent after intranasal administration as NE.

PMID- 24128123
TI  - Utility and pattern of positivity of p40 in the diagnosis of squamous cell
      carcinoma of the lung by cytology: the first study on fine needle aspiration
      smears.
AB  - OBJECTIVE: Immunohistochemistry for p40 has emerged as a clinically applicable
      tool with high sensitivity and specificity to distinguish lung adenocarcinoma and
      squamous cell carcinoma (SCC). It appears to be an excellent marker for squamous
      differentiation. Although application of p40 in cell blocks has been reported,
      its expression has not been described in cytology smears. The aim was to study
      the expression of p40 in fine needle aspirates of SCC of the lung and to analyse
      differences in immunoreactivity in variably differentiated SCC. METHODS: The
      study used aspirates of lung masses diagnosed as SCC over a period of 2 years.
      p40 immunocytochemistry was performed on destained Papanicolaou smears. Nuclear
      staining was semi-quantitatively evaluated as 0, 1 + , 2 +  and 3 +  based on the
      percentage positivity of tumour cells and was correlated with differentiation of
      the tumour. Adequate unmatched histology (50 biopsies) and cytology (25 smears)
      controls were taken for comparison. RESULTS: A total of 45 cases of primary and
      five cases of metastatic pulmonary SCC were identified. There were 17 well, 24
      moderately and nine poorly differentiated SCC. p40 immunoreactivity was 2-3 +  in
      all moderate and poorly differentiated tumours, however, negative to 1 +  in all
      well-differentiated carcinomas (P < 0.0001). CONCLUSION: p40 immunostain is a
      valuable stain in identifying lung SCCs and works well in aspiration smears. The
      pattern of positivity varies with the differentiation of the tumour and is seen
      prominently in higher grade SCC where in practice the need arises for
      distinguishing them from either poorly differentiated adenocarcinomas or non
      small cell carcinoma, not otherwise specified.

PMID- 24128124
TI  - Additive-mediated electrochemical synthesis of platelike copper crystals for
      methanol electrooxidation.
AB  - A room-temperature electrochemical approach to synthesizing anisotropic platelike
      copper microcrystals and nanocrystals in the presence of potassium bromide is
      presented. Morphological and elemental characterization was performed using SEM,
      TEM, and XRD to confirm the anisotropic morphology and crystal structure of the
      synthesized copper particles. A possible mechanism for explaining the anisotropic
      crystal growth is proposed on the basis of the preferential adsorption of bromide
      ions to selective crystal faces. The shape-dependent electrocatalytic property of
      copper particles is demonstrated by its enhanced catalytic activity for methanol
      oxidation. Further development of such anisotropic copper particles localized on
      an electrode surface will lead us to find a suitable alternative for noble metal
      based electrocatalysts for the methanol oxidation reaction relevant to fuel
      cells. 

PMID- 24128125
TI  - Benefits of sensory garden and horticultural activities in dementia care: a
      modified scoping review.
AB  - AIMS AND OBJECTIVES: To provide a review on the benefits associated with the use
      of sensory gardens and horticultural activities in dementia care. BACKGROUND:
      Maintaining quality of life is important in dementia care. Sensory gardens and
      horticultural activities are increasingly used in dementia care, yet their
      benefits are uncertain. DESIGN: A modified scoping review with descriptive
      analysis of selected empirical studies. METHODS: Systematic searches in Amed,
      CINAHL, MEDLINE, ISI Web of Science, Embase and Scopus were used. Search terms
      were the free-text concepts 'healing garden', 'horticultural therapy',
      'restorative garden' and 'wander garden' which were combined with dementia and
      Alzheimer. RESULTS: Sixteen studies were included with included participants
      ranging from eight to 129 participants. Research designs were case studies (n =
      2), survey (n = 1), intervention studies with pretest/post-test design (n = 11)
      and randomised controlled studies (n = 2). Of these 16 studies, eight examined
      the benefits of sensory gardens, seven examined horticultural therapy or
      therapeutic horticulture and one examined the use of plants indoors. This study
      offers a review of the research addressing benefits of sensory gardens,
      therapeutic horticulture, horticultural therapy and other purposeful use of
      plants in dementia care. The reported findings are mainly on issues related to
      behaviour, affect and well-being. The findings are in general mutually
      supportive, however, with some contradictory findings. In addition, sleep
      pattern, well-being and functional level seem to improve. CONCLUSIONS: These
      types of nonpharmacological interventions may improve well-being and affect and
      reduce the occurrence of disruptive behaviour. Additionally, the use of
      psychotropic drugs, incidents of serious falls, sleep and sleep pattern also seem
      to improve. RELEVANCE TO CLINICAL PRACTICE: To further improve the use of the
      existing or planned gardens, an educational programme for staff that also
      includes skill training is recommended.

PMID- 24128126
TI  - Small but thick enough--the Arabidopsis hypocotyl as a model to study secondary
      growth.
AB  - The continuous production of vascular tissues through secondary growth results in
      radial thickening of plant organs and is pivotal for various aspects of plant
      growth and physiology, such as water transport capacity or resistance to
      mechanical stress. It is driven by the vascular cambium, which produces inward
      secondary xylem and outward secondary phloem. In the herbaceous plant Arabidopsis
      thaliana (Arabidopsis), secondary growth occurs in stems, in roots and in the
      hypocotyl. In the latter, radial growth is most prominent and not obscured by
      parallel ongoing elongation growth. Moreover, its progression is reminiscent of
      the secondary growth mode of tree trunks. Thus, the Arabidopsis hypocotyl is a
      very good model to study basic molecular mechanisms of secondary growth. Genetic
      approaches have succeeded in the identification of various factors, including
      peptides, receptors, transcription factors and hormones, which appear to
      participate in a complex network that controls radial growth. Many of these
      players are conserved between herbaceous and woody plants. In this review, we
      will focus on what is known about molecular mechanisms and regulators of vascular
      secondary growth in the Arabidopsis hypocotyl. 

PMID- 24128127
TI  - Unique echocardiographic markers of anomalous origin of the left coronary artery
      from the pulmonary artery (ALCAPA) in the adult.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital heart defect in adults. We report a 38-year-old male
      presenting with exertional syncope. He was referred for the evaluation of
      multiple muscular ventricular septal defects diagnosed on an outpatient
      echocardiogram. Echocardiography revealed mild left ventricular enlargement,
      abnormal flow-pattern in the ventricular septum and dilatation of the right
      coronary artery. Pulsed-wave Doppler with sample volume placed in the coronary
      ostium showed systolic coronary flow predominancy. This unique finding is
      characteristic for ALCAPA and can differentiate it from other coronary anomalies.
      Coronary angiography confirmed ALCAPA syndrome. Surgical correction was planned. 

PMID- 24128129
TI  - Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward -
      report on the lymphoma workshop of the XVIth meeting of the European Association
      for Haematopathology and the Society for Hematopathology.
AB  - Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among
      the broad category of non-Hodgkin lymphomas. Owing to the lack of specific
      genetic alterations in the vast majority, most currently defined entities show
      overlapping morphological and immunophenotypic features, and therefore pose a
      challenge to the diagnostic pathologist. In the light of recent immunophenotypic,
      cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell
      lymphomas, the focus of the lymphoma workshop of the European Association for
      Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in
      October 2012 was to refine existing diagnostic criteria and clarify the borders
      between overlapping entities. The panel reviewed over 200 submitted cases, which
      were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T
      follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell
      lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell
      neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative
      diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post
      transplant lymphoproliferative disorders, and mimics. This report summarizes the
      discussions and conclusions of the workshop, which question current diagnostic
      criteria and provide recommendations for refining existing classifications. 

PMID- 24128128
TI  - Relationship between lymph node ratio and cancer-specific survival in a
      contemporary series of patients with penile cancer and lymph node metastases.
AB  - OBJECTIVE: To evaluate the association between lymph node ratio (LNR) and cancer
      specific survival (CSS) in a population of patients with penile cancer and lymph
      node metastases (LNM). PATIENTS AND METHODS: We evaluated 81 patients with
      pathologically determined LNM who were surgically treated at our institution
      between 2000 and 2012. We considered LNR both as a continuously coded and as a
      categorically coded variable. The minimum-P-value approach was used to determine
      the most significant LNR threshold. The Kaplan-Meier method was used to determine
      CSS rates, and univariable and multivariable Cox regression models were fitted to
      test the predictors of CSS. RESULTS: The median (interquartile range [IQR])
      numbers of positive and removed lymph nodes were 2 (1-4) and 22 (13-30),
      respectively. The median (IQR) LNR was 10.3 (6.3-16.6)% and the most significant
      LNR threshold was 22%. The median (IQR) follow-up was 26 (16-62) months. Overall,
      the 5-year CSS rate was 50.5%. After stratification according to LNR, 5-year CSS
      rates were 65.2% vs 9.6% in patients with LNR < 22% vs LNR >= 22%, respectively
      (P < 0.001). In multivariable Cox regression models, after adjusting for several
      established prognostic factors, LNR was as independent predictor of CSS
      (P<=0.012). Finally, LNR significantly improved the accuracy of multivariable Cox
      regression models by 4.9-10.5%. CONCLUSIONS: Although further investigations are
      needed to evaluate the relationship between tumour burden and treatment
      intensity, LNR may represent a powerful predictor of CSS in patients with penile
      cancer and pathologically determined LNM.

PMID- 24128130
TI  - Reliability in somatic cell count measurement of clinical mastitis milk using
      DeLaval cell counter.
AB  - Somatic cell counts (SCC) measurements are typically performed using quantitative
      methods, such as the Breed method (Breed) and the Fossomatic method (FSCC). The
      DeLaval cell counter (DCC) developed recently is a quantitative somatic cell
      counter with a low initial cost and superior portability. However, since the DCC
      was specifically developed for measuring SCC of <= 4 * 10(6) cells/mL milk from
      bulk tanks or individual cows, its reliability for estimating SCC that exceed
      this concentration has not yet been clarified. This study therefore examined
      whether it is possible to accurately measure SCC by diluting milk samples with
      initial SCC of 4 * 10(6) cells/mL, as seen in clinical mastitis milk. We
      collected milk samples from 99 quarters of 99 Holstein cows with clinical
      mastitis. These milk samples were diluted 10-fold with saline and thoroughly
      mixed before performing SCC measurement with the DCC. The correlation
      coefficients of SCC measured by the FSCC, Breed and DCC methods indicated strong
      correlations between each pair of methods. The findings showed that DCC can be
      used to identify bovine clinical mastitis milk and is useful as a quantitative
      SCC measurement device on farm sites.

PMID- 24128131
TI  - Beating heart mitral valve repair for a patient with previous coronary bypass: a
      case report and review of the literature.
AB  - Mitral valve reoperation, through a median sternotomy, for a patient with patent
      coronary bypass grafts is technically challenging and carries higher
      postoperative morbidity and mortality than a primary operation. We present a case
      of mitral valve repair using a beating heart technique under normothermic
      cardiopulmonary bypass that was performed 3 years after a coronary artery bypass
      operation. A limited (10 cm) right thoracotomy was made and cardiopulmonary
      bypass was conducted using the ascending aortic and femoral venous cannulation.
      The left atrium was opened while beating was maintained. Triangular resection of
      the prolapsed portion of the posterior leaflet and ring annuloplasty were
      performed. Completeness of the repair was verified by direct visualization under
      beating condition and transesophageal echocardiogram. This technique is a safe
      and feasible option for a mitral valve reoperation that excludes re-sternotomy,
      extensive pericardial dissection and aortic clamping, thereby minimizes risks of
      bleeding, graft injury and myocardial damage.

PMID- 24128132
TI  - Dual kidney transplant: a single-center experience and review of the literature.
AB  - OBJECTIVES: Adult dual kidney transplant is a strategy to overcome the imbalance
      between limited nephron mass supplied from an older donor and a recipient with a
      metabolic request. MATERIALS AND METHODS: In our report, we review the literature
      and present our single-center experience. From June 2007 until July 2012, nine
      hundred twenty-eight single and seventeen dual kidney transplants from deceased
      donors were performed. RESULTS: The average donor was 71.5 +/- 3.6 years of age
      with an average serum creatinine, creatinine clearance, and an average number of
      sclerotic glomeruli, 106.1 +/- 44.2 MUmol/L, 0.97 +/- 0.37 mL/s, and 22.4 +/-
      14.2. Immediate graft function and acute rejection episodes were observed in 75%
      and 6% of patients. The overall patient survival rates at 1 and 2 years after
      transplant were 93%. The overall graft survival rates at 1 and 2 years were 88%.
      CONCLUSIONS: Previous studies and our single-center experience suggest that the
      dual transplant procedure may help improve results of kidney transplants from
      expanded criteria donors and extend the donor pool by using kidneys that would be
      discarded otherwise.

PMID- 24128133
TI  - Antibody-mediated rejection and treatment in pediatric patients: one center's
      experience.
AB  - OBJECTIVES: Antibody-mediated rejection is a rare complication that often results
      in the loss of the kidney graft. Treatment options include plasmapheresis,
      intravenous immunoglobulin, and use of rituximab. MATERIALS AND METHODS: We
      retrospectively evaluated the data files from 86 pediatric renal transplant
      patients over the last 5 years. A biopsy was taken for each rejection episode.
      RESULTS: Seven patients (7.7%) developed antibody-mediated rejection. All
      patients with antibody-mediated rejection had histologic evidence of severe acute
      humoral rejection and extensive C4d staining in peritubular capillaries. Staining
      was diffuse (involving > 50% of peritubular capillaries) for 4 biopsies, and it
      was focal (involving < 50% of peritubular capillaries) for 3 biopsies. Twelve
      biopsies demonstrated at least 1 histologic feature associated with acute humoral
      rejection. Donor-specific antibodies were evaluated in recipients. The mean peak
      panel reactive antibody class 1 was 7.16% (range, 0%-86%). The mean time between
      rejection episodes and the transplant was 16.9 +/- 13.5 months. All patients were
      treated with high-dose intravenous methylprednisolone and intravenous
      immunoglobulin. Three patients recovered renal function rapidly after this
      treatment. Donor-specific antibodies were negative in these patients. Five
      sessions of plasmapheresis were used simultaneously in these 4 patients. In 3
      resistant patients, rituximab was prescribed after plasmapheresis and intravenous
      immunoglobulin. The presence of donor-specific antibodies was demonstrated in 4
      patients. Two patients were refractory to antibody-mediated rejection treatment
      and lost their transplants. One patient had interstitial fibrosis and tubular
      atrophy during the 16th month after her antibody-mediated rejection. Graft
      survival in patients with antibody-mediated rejection at the end of 1 year was
      71.4%. CONCLUSIONS: Early diagnosis and treatment with plasmapheresis,
      intravenous immunoglobulin, and rituximab may resolve antibody-mediated
      rejection. Although effective therapy is available for acute antibody-mediated
      rejection, the allograft remains at risk for chronic antibody-mediated rejection
      and shortened survival.

PMID- 24128134
TI  - Sirolimus conversion may suppress viral replication in hepatitis C virus-positive
      renal transplant candidates.
AB  - OBJECTIVES: Hepatitis C virus in renal transplant recipients is an independent
      risk factor for sickness and death. It has been shown that one might limit
      hepatitis C virus progression in liver transplant recipients with sirolimus-based
      immunosuppression. The mammalian target of rapamycin is an influential molecule
      for the anti-hepatitis C virus action of interferon. We report our experience
      with sirolimus conversion in hepatitis C virus-positive patients with chronic
      allograft nephropathy regarding hepatic and hematologic effects that might affect
      its future use. MATERIALS AND METHODS: Twenty-five patients who had received
      renal transplants with anti-hepatitis C virus-positive and normal liver function
      were enrolled. Ten patients had allograft dysfunction because of cyclosporine
      nephrotoxicity. Sirolimus was initiated at 2 mg/d and adjusted to 6 to 8 ng/mL.
      Cyclosporine was gradually tapered and then stopped; 15 patients were used as a
      control group. Sirolimus-related hepatitis was defined as a rise in liver
      transferases or alkaline phosphatase or bilirubin over twice the upper limit of
      normal. Viral replication was defined as elevated liver enzymes and increasing
      viral load and/or biopsy-proven hepatitis C virus active hepatitis. RESULTS:
      After conversion, there was a reduction of hemoglobin and hematocrit. In 1
      patient, the immunosuppressive regimen was changed back to cyclosporine owing to
      anemia and hepatotoxicity leading to prompt return of hematocrit and liver
      enzymes to their original values. One of 10 antihepatitis C virus-positive
      patients (10.0%) developed sirolimus-associated hepatotoxicity, compared with 2
      patients in the control group (13%). Sirolimus patients showed a significant
      decrease in the HCV PCR levels from 700 000 to 400 000 IU/mL; P < .001, compared
      to 680 000 to 660 000 IU/mL in cyclosporine patients; P = NS, with comparable
      levels of transaminases CONCLUSIONS: Our data suggest that sirolimus has the
      potential to suppress viral replication in hepatitis C virus-positive renal
      transplant candidates.

PMID- 24128135
TI  - First liver transplant in Qatar: an evolving program facing many challenges.
AB  - OBJECTIVES: Beginning to do liver transplants in a developing country is
      challenging. We report on the first few liver transplants performed in Qatar and
      discuss future exceptions and challenges facing our program. MATERIALS AND
      METHODS: The first liver transplant was performed in Qatar on December 6, 2011.
      Since starting the program, 4 deceased-donor liver transplants have been
      performed in Qatar. All recipients underwent a standard deceased-donor liver
      transplant procedure, which included a duct-to-duct biliary anastomosis without a
      veno-venous bypass. All liver transplants were performed at the Hamad Medical
      Corporation by a local team of surgeons without external assistance. RESULTS: The
      4 patients were all men, with a median age of 56 years (age range, 46-63 y).
      Indications for liver transplant included hepatitis C cirrhosis in 2 patients,
      and 1 patient with hepatitis B cirrhosis with hepatocellular carcinoma, and the
      other patient with cryptogenic liver cirrhosis. Median amount of blood transfused
      was 6 units (range, 0-10 U); median time spent in the intensive care unit was 2
      days (range, 2-5 d); median amount of time spent in the hospital was 10 days
      (range, 9-16 d). All 4 recipients have survived after a median follow-up of 438
      days (range, 33-602 d) and are enjoying a healthy life, with no significant
      posttransplant complications. CONCLUSIONS: A deceased-donor liver transplant can
      be performed in Qatar with no external assistance. However, a severe organ
      shortage remains the biggest obstacle facing us. Efforts should be directed
      toward improving the number and quality of available deceased donors in Qatar.
      Meanwhile, live-donor liver transplant may be the only way for us, going forward,
      to prevent deaths on the waiting list.

PMID- 24128136
TI  - Renal recovery after conversion to an everolimus-based immunosuppression in early
      and late heart transplant recipients: a 12-month analysis.
AB  - OBJECTIVES: Calcineurin inhibitor-induced nephrotoxicity reduces long-term
      patient survival after heart transplant. Proliferation signal inhibitors, in
      combination with or replacing calcineurin inhibitors, may preserve or improve
      renal function. We evaluated the effect of calcineurin inhibitor-reduction and
      withdrawal in everolimus-based immunosuppression on renal function after a heart
      transplant. MATERIALS AND METHODS: Twenty-four patients with creatinine clearance
      < 1 mL/s (60 mL/min) were switched from tacrolimus and mycophenolate mofetil to
      low-dose tacrolimus/everolimus if their heart transplant was <= 1 year ago (group
      1, n=13) and to everolimus/mycophenolate mofetil if their heart transplant was >
      1 year ago (group 2, n=11). Serum creatinine levels and calculated creatinine
      clearance were analyzed up to 12 months after conversion. RESULTS: The switch in
      immunosuppression was associated with a significant decrease/increase of serum
      creatinine/creatinine clearance in both groups between baseline and month 12
      (group 1, creatinine, 221.0 +/- 70.7 to 159.1 +/- 44.2 MUmol/L (2.5 +/- 0.8 to
      1.8 +/- 0.5 mg/dL); creatinine clearance, 0.75 +/- 0.45 to 1.01 +/- 0.50 mL/s
      (45.1 +/- 26.7 to 60.5 +/- 29.7 mL/min) (P < .01 each); group 2, creatinine,
      247.5 +/- 79.6 to 159.1 +/- 44.2 MUmol/L (2.8 +/- 0.9 to 1.8 +/- 0.5 mg/dL),
      creatinine clearance, 0.57 +/- 0.23 to 0.93 +/- 0.33 mL/s (34.1 +/- 13.8 to 55.7
      +/- 19.6 mL/min) [P < .05 each]) with no significant group difference in the
      creatinine and the creatinine clearance levels after switching. No acute
      rejections or deaths occurred during the 12-month follow-up. Four patients
      (36.4%) from group 2 and 1 patient (7.7%) from group 1 discontinued everolimus
      because of adverse events. CONCLUSIONS: Everolimus allows calcineurin inhibitor
      reduction and withdrawal after a heart transplant, resulting in improved renal
      function. However, adverse effects are common and lead to a high reconversion
      rate.

PMID- 24128137
TI  - Coexisting or underlying risk factors of hepatic veno-occlusive disease in
      pediatric hematopoietic stem cell transplant recipients receiving prophylaxis.
AB  - OBJECTIVES: To evaluate the characteristics of veno-occlusive disease in
      pediatric hematopoietic stem cell transplant recipients, and their effect as a
      prophylactic regimen on severity and outcome. MATERIALS AND METHODS: This study
      included 204 allogeneic hematopoietic stem cell transplants performed on 187
      children whose data retrospectively described the risk factors, prophylaxis, and
      treatment modalities of veno-occlusive disease. A prophylactic regimen composed
      of enoxaparin versus ursodeoxycholic acid and vitamin E was given to 167 of 204
      patients. RESULTS: Veno-occlusive disease developed in 22 patients (10.8%).
      Nineteen patients experienced veno-occlusive disease despite this prophylactic
      regimen. The prophylaxis seemed ineffective in preventing veno-occlusive disease
      (P = .657). Regarding risk factors, oral busulphan use, liposomal amphotericin B
      vancomycin treatment, and total parenteral nutrition were associated with an
      increased risk of veno-occlusive disease. Conversely, renal impairment also was
      associated with increased mortality in patients with veno-occlusive disease. The
      mortality rate in the first 100 days after a hematopoietic stem cell transplant
      was higher in the patients with veno-occlusive disease than it was in those
      without the disease. CONCLUSIONS: Our prophylactic regimen may have played a role
      in the fairly low incidence of veno-occlusive disease in a pediatric population
      with high-risk features.

PMID- 24128138
TI  - Trimethoprim/sulfamethoxazole-related acute psychosis in the second course of
      treatment after a stem cell transplant: case report and literature review.
AB  - The case report describes a woman who has an acute psychosis episode during the
      second course of trimethoprim/sulfamethoxazole therapy, after having an
      allogeneic hematopoietic stem cell transplant that favored a dose-related effect
      of this adverse effect. 

PMID- 24128139
TI  - Specific microorganism strains for achieving specific health targets in children
      undergoing hematopoietic stem cell transplant.

PMID- 24128141
TI  - Pregnancy-induced remodelling and enhanced endothelium-derived hyperpolarization
      type vasodilator activity in rat uterine radial artery: transient receptor
      potential vanilloid type 4 channels, caveolae and myoendothelial gap junctions.
AB  - In pregnancy, the vasculature of the uterus undergoes rapid remodelling to
      increase blood flow and maintain perfusion to the fetus. The present study
      determines the distribution and density of caveolae, transient receptor potential
      vanilloid type 4 channels (TRPV4) and myoendothelial gap junctions, and the
      relative contribution of related endothelium-dependent vasodilator components in
      uterine radial arteries of control virgin non-pregnant and 20-day late-pregnant
      rats. The hypothesis examined is that specific components of endothelium
      dependent vasodilator mechanisms are altered in pregnancy-related uterine radial
      artery remodelling. Conventional and serial section electron microscopy were used
      to determine the morphological characteristics of uterine radial arteries from
      control and pregnant rats. TRPV4 distribution and expression was examined using
      conventional confocal immunohistochemistry, and the contribution of endothelial
      TRPV4, nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type
      activity determined using pressure myography with pharmacological intervention.
      Data show outward hypertrophic remodelling occurs in uterine radial arteries in
      pregnancy. Further, caveolae density in radial artery endothelium and smooth
      muscle from pregnant rats was significantly increased by ~94% and ~31%,
      respectively, compared with control, whereas caveolae density did not differ in
      endothelium compared with smooth muscle from control. Caveolae density was
      significantly higher by ~59% on the abluminal compared with the luminal surface
      of the endothelium in uterine radial artery of pregnant rats but did not differ
      at those surfaces in control. TRPV4 was present in endothelium and smooth muscle,
      but not associated with internal elastic lamina hole sites in radial arteries.
      TRPV4 fluorescence intensity was significantly increased in the endothelium and
      smooth muscle of radial artery of pregnant compared with control rats by ~2.6-
      and 5.5-fold, respectively. The TRPV4 signal was significantly higher in the
      endothelium compared with the smooth muscle in radial artery of both control and
      pregnant rats, by ~5.7- and 2.7-fold, respectively. Myoendothelial gap junction
      density was significantly decreased by ~37% in radial artery from pregnant
      compared with control rats. Pressure myography with pharmacological intervention
      showed that NO contributes ~80% and ~30%, and the EDH-type component ~20% and
      ~70% of the total endothelium-dependent vasodilator response in radial arteries
      of control and pregnant rats, respectively. TRPV4 plays a functional role in
      radial arteries, with a greater contribution in those from pregnant rats. The
      correlative association of increased TRPV4 and caveolae density and role of EDH
      type activity in uterine radial artery of pregnant rats is suggestive of their
      causal relationship. The decreased myoendothelial gap junction density and lack
      of TRPV4 density at such sites is consistent with their having an integral,
      albeit complex, interactive role in uterine vascular signalling and remodelling
      in pregnancy. 

PMID- 24128140
TI  - Acetylation of lysine 92 improves the chaperone and anti-apoptotic activities of
      human alphaB-crystallin.
AB  - alphaB-Crystallin is a chaperone and an anti-apoptotic protein that is strongly
      expressed in many tissues, including the lens, retina, heart, and kidney. In the
      human lens, several lysine residues in alphaB-crystallin are acetylated. We have
      previously shown that such acetylation is predominant at lysine 92 (K92) and
      lysine 166 (K166). We have investigated the effect of lysine acetylation on the
      structure and functions of alphaB-crystallin by the specific introduction of an
      N(epsilon)-acetyllysine (AcK) mimic at K92. The introduction of AcK slightly
      altered the secondary and tertiary structures of the protein. The introduction of
      AcK also resulted in an increase in the molar mass and hydrodynamic radius of the
      protein, and the protein became structurally more open and more stable than the
      native protein. The acetyl protein acquired higher surface hydrophobicity and
      exhibited 25-55% higher chaperone activity than the native protein. The acetyl
      protein had more client protein binding per subunit of the protein and higher
      binding affinity relative to that of the native protein. The acetyl protein was
      at least 20% more effective in inhibiting chemically induced apoptosis than the
      native protein. Molecular modeling suggests that acetylation of K92 makes the
      "alpha-crystallin domain" more hydrophobic. Together, our results reveal that the
      acetylation of a single lysine residue in alphaB-crystallin makes the protein
      structurally more stable and improves its chaperone and anti-apoptotic
      activities. Our findings suggest that lysine acetylation of alphaB-crystallin is
      an important chemical modification for enhancing alphaB-crystallin's protective
      functions in the eye. 

PMID- 24128143
TI  - Bayesian spatial transformation models with applications in neuroimaging data.
AB  - The aim of this article is to develop a class of spatial transformation models
      (STM) to spatially model the varying association between imaging measures in a
      three-dimensional (3D) volume (or 2D surface) and a set of covariates. The
      proposed STM include a varying Box-Cox transformation model for dealing with the
      issue of non-Gaussian distributed imaging data and a Gaussian Markov random field
      model for incorporating spatial smoothness of the imaging data. Posterior
      computation proceeds via an efficient Markov chain Monte Carlo algorithm.
      Simulations and real data analysis demonstrate that the STM significantly
      outperforms the voxel-wise linear model with Gaussian noise in recovering
      meaningful geometric patterns. Our STM is able to reveal important brain regions
      with morphological changes in children with attention deficit hyperactivity
      disorder. 

PMID- 24128144
TI  - Validation of the postnatal perceived stress inventory in a French speaking
      population of primiparous women.
AB  - OBJECTIVE: To develop a Postnatal Perceived Stress Inventory (PNPSI) and assess
      its psychometric properties. DESIGN: Cross-sectional quantitative study. SETTING:
      One nurse-managed labor and delivery unit in a university hospital in a major
      metropolitan area. PARTICIPANTS: One hundred seventy-nine (179) primiparous
      French speaking women who gave birth at term. METHODS: The PNPSI was validated at
      6 weeks postpartum. Its predictive validity for depression and anxiety was
      assessed at the same time. RESULTS: The exploratory analysis revealed a 19-item
      structure divided into six factors. This inventory has good internal consistency
      (Cronbach's alpha = .815). The predictive validity shows that the PNPSI
      significantly predicts depression and anxiety at 6 weeks postpartum, and that
      certain factors are particularly prominent. CONCLUSION: The PNPSI's psychometric
      properties make it a useful tool for future research to evaluate interventions
      for perceived stress during the postnatal period. Its predictive power for
      depression indicates that it is also a promising tool for clinical settings.

PMID- 24128145
TI  - Cyclic 3-alkyl pyridinium alkaloid monomers from a New Zealand Haliclona sp.
      marine sponge.
AB  - Bioassay and NMR approaches have been used to guide the isolation of one known
      and two new cyclic 3-alkyl pyridinium alkaloid (3-APA) monomers from the New
      Zealand marine sponge Haliclona sp. The new compounds, dehydrohaliclocyclins C
      (3) and F (4), are the first reported examples of cyclic 3-APA monomers with
      unsaturation in the alkyl chain. The known compound haliclocyclin C (2) was also
      isolated from a mixture with 4. The structures of compounds 2-4 were elucidated
      using NMR spectroscopy, mass spectrometry, and chemical degradation. 

PMID- 24128146
TI  - StreamingTrim 1.0: a Java software for dynamic trimming of 16S rRNA sequence data
      from metagenetic studies.
AB  - Next-generation sequencing technologies are extensively used in the field of
      molecular microbial ecology to describe taxonomic composition and to infer
      functionality of microbial communities. In particular, the so-called barcode or
      metagenetic applications that are based on PCR amplicon library sequencing are
      very popular at present. One of the problems, related to the utilization of the
      data of these libraries, is the analysis of reads quality and removal (trimming)
      of low-quality segments, while retaining sufficient information for subsequent
      analyses (e.g. taxonomic assignment). Here, we present StreamingTrim, a DNA reads
      trimming software, written in Java, with which researchers are able to analyse
      the quality of DNA sequences in fastq files and to search for low-quality zones
      in a very conservative way. This software has been developed with the aim to
      provide a tool capable of trimming amplicon library data, retaining as much as
      taxonomic information as possible. This software is equipped with a graphical
      user interface for a user-friendly usage. Moreover, from a computational point of
      view, StreamingTrim reads and analyses sequences one by one from an input fastq
      file, without keeping anything in memory, permitting to run the computation on a
      normal desktop PC or even a laptop. Trimmed sequences are saved in an output
      file, and a statistics summary is displayed that contains the mean and standard
      deviation of the length and quality of the whole sequence file. Compiled
      software, a manual and example data sets are available under the BSD-2-Clause
      License at the GitHub repository at https://github.com/GiBacci/StreamingTrim/. 

PMID- 24128147
TI  - New phenanthrene derivatives with nitric oxide inhibitory and radical-scavenging
      activities from Pholidota imbricata Hook.
AB  - One new phenanthrene derivative phoimbrtol A (1) with seven known compounds,
      loddigesiinol B (2), shanciol B (3), (-)-medioresinol (4), (-)-pinoresinol (5),
      quercetin 3-O-beta-L-arabinofuranoside (6), luteolin 7-O-beta-glucoside (7) and
      platycaryanin D (8) have been isolated from the ethyl acetate extract of the air
      dried whole plant of Pholidota imbricata Hook. Their inhibitory effects on nitric
      oxide (NO) production and 1,1-diphenyl-2-picrylhydrazil (DPPH) radical scavenging
      activity were examined. Among these compounds, 8 exhibited the most potent
      activity at NO production inhibitory assay and DPPH radical scavenging assay,
      stronger than those of the familiar antioxidative agents, quercetin and
      resveratrol.

PMID- 24128148
TI  - Attentional bias for nondrug reward is magnified in addiction.
AB  - Attentional biases for drug-related stimuli play a prominent role in addiction,
      predicting treatment outcomes. Attentional biases also develop for stimuli that
      have been paired with nondrug rewards in adults without a history of addiction,
      the magnitude of which is predicted by visual working-memory capacity and
      impulsiveness. We tested the hypothesis that addiction is associated with an
      increased attentional bias for nondrug (monetary) reward relative to that of
      healthy controls, and that this bias is related to working-memory impairments and
      increased impulsiveness. Seventeen patients receiving methadone-maintenance
      treatment for opioid dependence and 17 healthy controls participated.
      Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11; Patton,
      Stanford, & Barratt, 1995), visual working-memory capacity was measured as the
      ability to recognize briefly presented color stimuli, and attentional bias was
      measured as the magnitude of response time slowing caused by irrelevant but
      previously reward-associated distractors in a visual-search task. The results
      showed that attention was biased toward the distractors across all participants,
      replicating previous findings. It is important to note, this bias was
      significantly greater in the patients than in the controls and was negatively
      correlated with visual working-memory capacity. Patients were also significantly
      more impulsive than controls as a group. Our findings demonstrate that patients
      in treatment for addiction experience greater difficulty ignoring stimuli
      associated with nondrug reward. This nonspecific reward-related bias could
      mediate the distracting quality of drug-related stimuli previously observed in
      addiction.

PMID- 24128149
TI  - The effects of alcohol expectancy priming on group bonding.
AB  - According to alcohol expectancy theory, drinking-related information is stored in
      memory and, when cue activated, influences alcohol-related behavior. Priming of
      alcohol cues and expectancies has been shown to elicit both drinking and
      nonconsumptive behavior associated with alcohol consumption, such as willingness
      to meet with a stranger and aggression. These social influence effects have been
      shown to be moderated by individual differences in alcohol expectancies. In the
      present study, we tested whether an alcohol prime would facilitate social group
      bonding even in the absence of consumption, and whether such group bonding would
      be moderated by individually held social expectancies. One hundred twenty
      undergraduates (75% female) completed an alcohol expectancy measure prior to
      participation. Participants were primed with either alcohol or neutral beverage
      words and completed a collaborative group activity followed by questionnaires
      measuring perceived group cohesion. Several interactions were found between
      condition and expectancy reflecting that those in the alcohol prime condition
      with higher social alcohol expectancies reported greater cohesion on task
      related, but not emotion-related, group measures. These findings underscore the
      complexity of the impact of expectancy and social behavior on drinking: the
      priming of alcohol expectancies may activate aspects of pro-social behavior,
      which may influence drinking, which in turn may feedback to positively reinforce
      social expectancies.

PMID- 24128151
TI  - Direct measurements of effect of counterion concentration on mechanical
      properties of cationic vesicles.
AB  - Theoretical analyses of charged membranes in aqueous solutions have long
      predicted that the electric double layer surrounding them contributes
      significantly to their mechanical properties. Here we report the first, direct
      experimental measurements of the effect of counterion concentration on the
      bending and area expansion modulus of cationic surfactant vesicles. Using the
      classical technique of micropipet aspiration coupled with a modified experimental
      protocol that is better suited for cationic vesicles, we successfully measure the
      mechanical properties of a double-tailed cationic surfactant,
      diethylesterdimethyl ammonium chloride (diC18:1 DEEDMAC) in CaCl2 solutions. It
      is observed that the area expansion modulus of the charged membrane exhibits no
      measurable dependence on the counterion concentration, in accordance with
      existing models of bilayer elasticity. The measured bending modulus, however, is
      found to vary nonmonotonically and exhibits a minimum in its variation with
      counterion concentration. The experimental results are interpreted based on
      theoretical calculations of charged and bare membrane mechanics. It is determined
      that the initial decrease in bending modulus with increasing counterion
      concentration may be attributed to a decreasing double layer thickness, while the
      subsequent increase is likely due to an increasing membrane thickness. These
      mechanical moduli measurements qualitatively confirm, for the first time,
      theoretical predictions of a nonmonotonic behavior and the opposing effects of
      ionic strength on the bending rigidity of charged bilayers. 

PMID- 24128150
TI  - DNA methylation within the I.4 promoter region correlates with CYPl19A1 gene
      expression in human ex vivo mature omental and subcutaneous adipocytes.
AB  - BACKGROUND: DNA methylation at specific CpG sites within gene promoter regions is
      known to regulate transcriptional activity in vitro. In human adipose tissue,
      basal transcription of the aromatase (CYP19A1) gene is driven primarily by the
      I.4 promoter however the role of DNA methylation in regulating expression in ex
      vivo mature adipocytes is unknown. This observational study reports the
      correlation of DNA methylation within the I.4 promoter region of human mature
      subcutaneous and omental adipocytes with aromatase expression and body
      composition measures. METHODS: Omental and subcutaneous adipose tissue were
      collected from 25 obese subjects undergoing bariatric surgery and the mature
      adipocyte fraction purified. DNA methylation status of 5 CpG sites within a 550
      base pair region encompassing the transcription start site (TSS) of promoter I.4
      was determined using pyrosequencing. Relative aromatase and I.4 promoter specific
      mRNA expression was determined by qRT-PCR and whole body DXA performed in 25
      participants. RESULTS: Site-specific DNA methylation varied from 21 +/- 10% to 81
      +/- 11%. In omental adipocytes percentage methylation at the I.4.1 and I.4.2 CpG
      sites, but not other nearby sites, was negatively correlated with relative
      aromatase mRNA expression (R = - 0.52, P = 0.017 and R = - 0.52, P = 0.015). In
      contrast subcutaneous adipocytes percentage DNA methylation at the I.4.3 and
      I.4.5 sites were positively correlated with relative aromatase mRNA expression (R
      = 0.47, P = 0.022 and R = 0.55, P = 0.004). In a small subset of patients DNA
      methylation at the I.4.5 site was also positively correlated with whole body lean
      mass, bone mineral content and density. CONCLUSIONS: In conclusion in mature
      adipocytes, the primary source of estradiol after menopause, increasing DNA
      methylation was correlated with aromatase mRNA expression and thus estradiol
      biosynthesis. These findings support a tissue-specific epigenetic regulation of
      the basal promoter activity in mature adipocytes; the mechanisms influencing this
      regulation and its physiological role remain to be elucidated.

PMID- 24128152
TI  - Two demyelinating diseases in the brain of a single patient, PML and MS: how to
      minimize 'one' while treating the 'other'.

PMID- 24128153
TI  - Recent advances in immunotherapy: the active treatment of food allergy on the
      horizon.

PMID- 24128156
TI  - Characterizing wheeze phenotypes to identify endotypes of childhood asthma, and
      the implications for future management.
AB  - It is now a commonly held view that asthma is not a single disease, but rather a
      set of heterogeneous diseases sharing common symptoms. One of the major
      challenges in treating asthma is understanding these different asthma phenotypes
      and their underlying biological mechanisms. This review gives an epidemiological
      perspective of our current understanding of the different phenotypes that develop
      from birth to childhood that come under the umbrella term 'asthma'. The review
      focuses mainly on publications from longitudinal birth cohort studies where the
      natural history of asthma symptoms is observed over time in the whole population.
      Identifying distinct pathophysiological mechanisms for these different phenotypes
      will potentially elucidate different asthma endotypes, ultimately leading to more
      effective treatment and management strategies. 

PMID- 24128157
TI  - Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance
      and impact on treatment response.
AB  - TNF inhibitors and anti-p40IL12/23 monoclonal antibodies are efficacious
      treatments for moderate-to-severe psoriasis. However, the formation of anti-drug
      antibodies (ADA) with biologics may prevent patients from achieving a full
      clinical response. ADA have been reported in patients treated with etanercept,
      infliximab, adalimumab or ustekinumab at rates of 0-18.3%, 5.4-43.6%, 8.8-44.8%
      and 3.8-5.4%, respectively. Antibodies against etanercept have no apparent
      effects on clinical response, whereas antibodies against infliximab or adalimumab
      have been associated with diminished clinical response. The significance of ADA
      against ustekinumab is yet to be determined. Data regarding management strategies
      to counteract ADA formation and their effects are limited in psoriasis patients.
      However, some evidence suggests that concomitant immunomodulators such as
      methotrexate may suppress ADA development in psoriasis. ADA specific to one
      biologic do not appear to carry cross-linking potential with other biologic
      agents. ADA formation needs to be considered as a possible factor contributing to
      diminished response from biologic agents. 

PMID- 24128158
TI  - Common variable immunodeficiency in adults: current diagnostic protocol and
      laboratory measures.
AB  - Common variable immunodeficiency (CVID) is one of the most common symptomatic
      primary immune defects in adults. Unfortunately, the diagnosis of CVID is often
      delayed because of its variable presentations and manifestations. Sincere efforts
      from experts in the field of primary immunodeficiency disorders all over the
      world have made us wiser regarding the clinical features, associated
      complications and long-term outcome of the disease. However, a systematic
      compilation of diagnostic protocols and laboratory measures is desirable. The
      present review highlights in brief the immunological and molecular defects
      characterizing adult CVID along with a comprehensive discussion on currently
      followed laboratory criteria and methods used to identify these cases. The
      article may benefit the clinicians, immunologists, infectious disease
      specialists, pulmonary medicine specialists, gastroenterologists, dermatologists
      and other physicians who are involved in the team management of the patients with
      CVID. 

PMID- 24128155
TI  - Clinical view on the importance of dendritic cells in asthma.
AB  - Allergic asthma is characterized by airway hyperresponsiveness and inflammation
      and may lead to airway remodeling in uncontrolled cases. Genetic predisposition
      to an atopic phenotype plays a major component in the pathophysiology of asthma.
      However, with tremendous role of epigenetic factors and environmental stimuli in
      precipitating an immune response, the underlying pathophysiological mechanisms
      are complicated. Dendritic cells are principal antigen-presenting cells and
      initiators of the immune response in allergic asthma. Their phenotype, guided by
      multiple factors may dictate the immune reaction to an allergic or tolerogenic
      response. Involvement of the local cytokine milieu, microbiome and interplay
      between immune cells add dimension to the fate of immune response. In addition to
      allergen exposure, these factors modulate DC phenotype and function. In this
      article, integration of many factors and pathways associated with the recruitment
      and activation of DCs in the pathophysiology of allergic asthma is presented in a
      clinical and translational manner. 

PMID- 24128159
TI  - Novel advances in the diagnosis and treatment of neuromyelitis optica: is there a
      need to redefine the gold standard?
AB  - Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous
      system characterized by severe attacks of optic neuritis and myelitis and, unlike
      multiple sclerosis, was initially thought to spare the brain in the early stages.
      The term NMO spectrum disorder (NMOSD) was recently used to qualify restricted
      forms of the disorder, which include recurrent optic neuritis, relapsing
      transverse myelitis and some encephalitic/brainstem presentations associated with
      positive aquaporin4 antibodies. It was also recently found that other
      immunological targets such as myelin oligodendrocyte glycoprotein (MOG) may be
      associated with seronegative NMO patients. In the present study, we detail the
      moving concept of NMOSD from the recent years and propose some therapeutic
      strategies that are clearly different compared with multiple sclerosis treatment.

PMID- 24128160
TI  - Cardiovascular comorbidities in antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is an autoimmune disease characterized by venous and/or
      arterial thrombosis and/or recurrent fetal loss and the presence of
      antiphospholid antibodies. Among the causes of death of antiphospholipid syndrome
      there are the myocardial infarction and stroke. Comorbidities could worsen the
      evolution of these patients, and the knowledge about these situations could
      prevent or minimizethe risks associated with the disease. In this article, we
      review the literature about cardiovascular comorbidities, such as traditional
      risk factors for atherosclerosis, metabolic syndrome and vitamin D deficiency,
      and how these could influence the prognosis of antiphospholipid syndrome
      patients. 

PMID- 24128161
TI  - Advances in hematopoietic stem cell transplantation for primary immunodeficiency.
AB  - The transplantation of hematopoietic stem cells in patients with primary
      immunodeficiencies has improved significantly over the last 40 years. In
      favorable circumstances when there is minimal or no infection present, no end
      organ damage and the availability of a well HLA-matched donor, survival and cure
      reaches 90%. Barriers to further success include late identification of disease,
      with accumulation of infection- and inflammation-related organ damage, stem cell
      manipulation when there is no HLA-matched donor, toxicity of conditioning
      regimens and prediction and treatment of graft-versus-host disease. This review
      will outline recent developments in conditioning regimens, stem cell source
      manipulation and early detection and treatment of graft-versus-host disease, with
      a particular emphasis on patients with primary immunodeficiency. 

PMID- 24128162
TI  - Psoriasis vulgaris associated with Vogt-Koyanagi-Harada syndrome.

PMID- 24128163
TI  - False action memories in older adults: relationship with executive functions?
AB  - Merely observing another person performing an action can make young people later
      misremember having performed this action themselves (the observation-inflation
      effect). We examined this type of memory error in healthy older adults. Overall,
      both young and older adult groups showed robust observation inflation. Although
      the number of people committing observation-inflation errors did not differ
      between age groups, those older adults who were prone to this illusion showed a
      greater observation-inflation effect compared to the corresponding young. At the
      same time, observation also had beneficial effects on subsequent action memory,
      especially in older adults. Surprisingly, executive functioning was not
      correlated with the degree to which older adults made observation-inflation
      errors, but it was related to the degree to which older adults benefited from
      observation. We consider accounts of observation inflation based on source
      monitoring, familiarity misattribution, and motor simulation.

PMID- 24128164
TI  - Epigenetic dysregulation in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease
      that affects multiple organs and is characterized by episodic flares and elevated
      morbidity. The etiology of SLE is only partly known. In this context, recent
      attention has been paid to the importance of environmentally induced epigenetic
      modifications as significant contributors to the disease pathogenesis in
      genetically predisposed individuals. Here we review what is currently known on
      the role of epigenetics in SLE, and the investigations aimed at possibly
      targeting epigenetic mechanisms and/or related biomarkers to improve the
      monitoring, management and, ultimately, the prognosis of SLE.

PMID- 24128165
TI  - Rational defect passivation of Cu2ZnSn(S,Se)4 photovoltaics with solution
      processed Cu2ZnSnS4:Na nanocrystals.
AB  - An effective defect passivation route has been demonstrated in the rapidly
      growing Cu2ZnSn(S,Se)4 (CZTSSe) solar cell device system by using Cu2ZnSnS4:Na
      (CZTS:Na) nanocrystals precursors. CZTS:Na nanocrystals are obtained by
      sequentially preparing CZTS nanocrystals and surface decorating of Na species,
      while retaining the kesterite CZTS phase. The exclusive surface presence of
      amorphous Na species is proved by X-ray photoluminescence spectrum and
      transmission electron microscopy. With Na-free glasses as the substrate, CZTS:Na
      nanocrystal-based solar cell device shows 50% enhancement of device performance
      (~6%) than that of unpassivated CZTS nanocrystal-based device (~4%). The enhanced
      electrical performance is closely related to the increased carrier concentration
      and elongated minority carrier lifetime, induced by defect passivation. Solution
      incorporation of extrinsic additives into the nanocrystals and the corresponding
      film enables a facile, quantitative, and versatile approach to tune the defect
      property of materials for future optoelectronic applications. 

PMID- 24128166
TI  - Clinical outcome and cyclo-oxygenase-2 expression in five dogs with solar
      dermatitis/actinic keratosis treated with firocoxib.
AB  - BACKGROUND: The conversion of arachidonic acid into prostaglandin is catalysed by
      the cyclo-oxygenases (COX-1/COX-2). Several studies indicate that COX-2 is
      overexpressed in actinic keratosis in humans and dogs. Firocoxib is a COX-2
      selective inhibitor that blocks the biochemical activity of COX-2.
      HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of firocoxib (5 mg/kg orally once
      daily) for the treatment of dogs with solar dermatitis/actinic keratosis.
      METHODS: Firocoxib 5 mg/kg was given orally once daily for 180 days to five dogs
      with clinical signs and histopathological lesions consistent with solar
      dermatitis/actinic keratosis. On days 0, 50 and 180, the severity of erythema,
      skin shine, induration and the number of comedones were evaluated by a clinical
      scoring system. On the same days, samples were collected for histopathology from
      'target lesions' and COX-2 expression was evaluated by immunohistochemistry.
      RESULTS: The clinical follow-up showed that four of five dogs improved with the
      treatment; improvement in terms of histological findings was correlated with the
      regularization of the epidermal proliferation rather than the recovery of dermal
      changes. CONCLUSIONS AND CLINICAL IMPORTANCE: A role for COX-2 might thus be
      hypothesized in the pathogenesis of canine solar dermatitis.

PMID- 24128167
TI  - Velocity dependent passive sampling for monitoring of micropollutants in dynamic
      stormwater discharges.
AB  - Micropollutant monitoring in stormwater discharges is challenging because of the
      diversity of sources and thus large number of pollutants found in stormwater.
      This is further complicated by the dynamics in runoff flows and the large number
      of discharge points. Most passive samplers are nonideal for sampling such systems
      because they sample in a time-integrative manner. This paper reports test of a
      flow-through passive sampler, deployed in stormwater runoff at the outlet of a
      residential-industrial catchment. Momentum from the water velocity during runoff
      events created flow through the sampler resulting in velocity dependent sampling.
      This approach enables the integrative sampling of stormwater runoff during
      periods of weeks to months while weighting actual runoff events higher than no
      flow periods. Results were comparable to results from volume-proportional samples
      and results obtained from using a dynamic stormwater quality model (DSQM). The
      paper illustrates how velocity-dependent flow-through passive sampling may
      revolutionize the way stormwater discharges are monitored. It also opens the
      possibility to monitor a larger range of discharge sites over longer time periods
      instead of focusing on single sites and single events, and it shows how this may
      be combined with DSQMs to interpret results and estimate loads over extended time
      periods. 

PMID- 24128168
TI  - Impact of the type of ureteroileal anastomosis on renal function measured by
      diuretic scintigraphy: long-term results of a prospective randomized study.
AB  - OBJECTIVE: To determine the long-term effects of the direct refluxing-type
      ureteroileal anastomosis technique with those of an antireflux technique on
      individual renal units, using diuretic scintigraphy in a prospectively randomized
      study. PATIENTS AND METHODS: Between 2002 and 2006, a prospective randomized
      study was conducted on 102 patients undergoing radical cystectomy and urinary
      diversion. In every patient, both ureters were randomized to be implanted using a
      direct refluxing technique or an antireflux, serous-lined extramural tunnel
      (SLET) technique. Renal function (RF) was evaluated using (99m)Tc-MAG-3 diuretic
      scintigraphy. The serial changes in corrected glomerular filtration rate (cGFR)
      for each technique and for each side were compared. RESULTS: Over a median follow
      up of 6 years, the patients in both the direct refluxing and the SLET technique
      groups were found to have a significant reduction in mean (SD) cGFR between
      baseline and last follow-up: cGFR decreased from 59.4 (12.4) to 45.6 (15.3)
      mL/min (P < 0.001) and from 54.3 (11.2) to 46.3 (12.8) mL/min (P = 0.002),
      respectively. Five patients (4.9%) in the SLET group developed obstruction (four
      left-sided and one right-sided) compared with one (0.9%) in the direct refluxing
      group (right-sided). The onset of obstruction was noted 1-7 months after radical
      cystectomy. There was no significant difference between the groups in reductions
      in cGFR across the timepoints. Comparison of the two techniques according to the
      side of ureter implantation showed that the direct refluxing technique trended
      towards better functional outcomes on the left side. CONCLUSIONS: There was no
      observed difference in the RF of individual renal units between the SLET and the
      direct refluxing groups in the long term. The need to incorporate an antireflux
      technique should be questioned and tailored according to the surgeon's experience
      and confidence.

PMID- 24128169
TI  - Daniel has fallen into a muddy puddle--schadenfreude or sympathy?
AB  - The present study investigated the experience of schadenfreude among children.
      Participants were 4- to 8-year-old children (n = 100) who were told stories of
      another child experiencing a misfortune while pursuing a morally positive versus
      morally negative goal. Schadenfreude, sympathy, and helping behaviour towards the
      suffering child were assessed. Results showed that beginning at the age of 4,
      emotional and behavioural reactions towards a misfortune of another child were
      predicted by the moral valence of the other child's goal. Furthermore, morally
      negative goals decreased helping behaviour and morally positive goals increased
      helping behaviour. Multilevel mediation analysis revealed that the relation
      between goal valence and helping behaviour was mediated by both schadenfreude and
      sympathy. However, those effects were especially pronounced in older children.

PMID- 24128170
TI  - National and ethnic identification, intergroup attitudes, and sport participation
      in the context of the London Olympics.
AB  - In the run-up to the 2012 London Olympics, the sense of national identity was
      salient. We tested children (N = 401) aged 5-15 years living near the Olympic
      site on national (British) and ethnic identification, national ingroup and
      outgroup attitudes, and sport participation. It was found that the strength of
      British identification peaked at age 9 years, but the strength of ethnic
      identification remained stable with age. Both liking for, and stereotyping of,
      different national groups diverged from age 9 years, but whilst stereotyping
      remained diverged liking converged by 15 years. The in group was one of the most
      liked, but one of the least positively stereotyped groups. Sport participation
      declined with age and was higher among boys, whilst the lowest socio-economic
      group showed the greatest discrepancy between normal and recent reported
      participation. The strength of British identification was associated with liking
      for, and stereotyping of, the British as well as sport participation, but the
      degree of associations varied between different groups of children.

PMID- 24128171
TI  - Fulfilment of intention and desire in children's judgements of emotion for
      sociomoral events.
AB  - This study investigated whether children appreciate that enacting an intention
      can emotionally affect an agent separately from whether the agent's desire is
      fulfilled. Children ages 5-11 years and adults heard several vignettes about an
      agent who intended to take another child's toy in which the agent's intention was
      either enacted or blocked and desire was fulfilled or unfulfilled. The effect of
      intention on judgements of the agent's emotion varied according to desire
      fulfilment and age. Overall, participants judged that an agent who acted
      intentionally to fulfil a desire felt happier than an agent whose intention was
      blocked. When the agent's desire was unfulfilled, the effect of enacting an
      intention varied by age. Five- to 6-year-olds judged that acting intentionally
      could decrease the negative emotion associated with an unfulfilled desire. The
      findings show relatively early appreciation of intentionality in children's
      judgements of emotion. Happy victimizer attributions decreased between 5 and 8
      years, but attributions of positive emotion to transgressors did not vary by
      intentionality. The relationships between intentionality, agency, and emotion are
      discussed.

PMID- 24128172
TI  - The relationships between quantity-number competencies, working memory, and
      phonological awareness in 5- and 6-year-olds.
AB  - In this study, the interdependencies among phonological awareness, verbal working
      memory components, and early numerical skills in children 1 year before school
      entry are addressed. Early numerical skills were conceptualized as quantity
      number competencies (QNC) at both basic (QNC Level 1) and advanced (QNC Level 2)
      levels. In a sample of 1,343 children aged 5 and 6, structural equation modelling
      provided support for the isolated number words hypothesis (Krajewski & Schneider,
      2009, J. Exp. Child Psychol., 103, 516-531). This hypothesis claims that
      phonological awareness contributes to the acquisition of QNC Level 1, such as
      learning the number word sequence, but not of QNC Level 2, which requires the
      linkage of number words to quantities. In addition, phonological awareness relied
      on verbal working memory, especially with regard to the phonological loop,
      central executive, and episodic buffer. The results were congruent with the idea
      that phonological awareness mediates the impact of verbal working memory on QNCs.
      The relationships between verbal working memory, phonological awareness, and QNCs
      were comparable in monolingual and bilingual children.

PMID- 24128173
TI  - Object processing for action across childhood.
AB  - Human adults process and select the opportunities for action in their environment
      rapidly, efficiently, and effortlessly. While several studies have revealed
      substantial improvements in object recognition skills, motor abilities, and
      control over the motor system during late childhood, surprisingly little is known
      about how object processing for action develops during this period. This study
      addresses this issue by investigating how the ability to ignore actions
      potentiated by a familiar utensil develops between ages 6 and 10 years. It is the
      first study to demonstrate that (1) the mechanisms that transform a graspable
      visual stimulus into an object-appropriate motor response are in place by the
      sixth year of life and (2) graspable features of an object can facilitate and
      interfere with manual responses in an adult-like manner by this age. The results
      suggest that there may be distinct developmental trajectories for the ability to
      ignore motor responses triggered by visual affordances and the stimulus response
      compatibility effects typically assessed with Simon tasks.

PMID- 24128174
TI  - Low-frequency human platelet antigens as triggers for neonatal alloimmune
      thrombocytopenia.
AB  - BACKGROUND: Twenty-four low-frequency human platelet antigens (LFHPAs) have been
      implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We
      performed studies to define more fully how often these antigens trigger maternal
      immunization leading to NAIT. STUDY DESIGN AND METHODS: In a Phase 1 study,
      fathers of selected NAIT cases not resolved by serologic testing but thought to
      have a high likelihood of NAIT on clinical and serologic grounds were typed for
      LFHPAs by DNA sequencing. In a Phase 2 study, high-throughput methods were used
      to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of
      1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a
      population racially/ethnically similar to the fathers. RESULTS: In Phase 1,
      LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found
      in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal
      samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the
      populations studied and was the only LFHPA that was significantly more common in
      fathers than in mothers of affected infants (p = 0.02). CONCLUSIONS: Maternal
      immunization against recognized LFHPAs accounts for only a small fraction of the
      cases of apparent NAIT not resolved by standard serologic testing. Typing of the
      fathers of such cases for LFHPAs is likely to be rewarding only when a maternal
      antibody specific for a paternal platelet glycoprotein is demonstrated and/or
      there is compelling clinical evidence for NAIT.

PMID- 24128175
TI  - Competition between Forster resonance energy transfer and electron transfer in
      stoichiometrically assembled semiconductor quantum dot-fullerene conjugates.
AB  - Understanding how semiconductor quantum dots (QDs) engage in photoinduced energy
      transfer with carbon allotropes is necessary for enhanced performance in solar
      cells and other optoelectronic devices along with the potential to create new
      types of (bio)sensors. Here, we systematically investigate energy transfer
      interactions between C60 fullerenes and four different QDs, composed of CdSe/ZnS
      (type I) and CdSe/CdS/ZnS (quasi type II), with emission maxima ranging from 530
      to 630 nm. C60-pyrrolidine tris-acid was first coupled to the N-terminus of a
      hexahistidine-terminated peptide via carbodiimide chemistry to yield a C60
      labeled peptide (pepC60). This peptide provided the critical means to achieve
      ratiometric self-assembly of the QD-(pepC60) nanoheterostructures by exploiting
      metal affinity coordination to the QD surface. Controlled QD-(pepC60)N
      bioconjugates were prepared by discretely increasing the ratio (N) of pepC60
      assembled per QD in mixtures of dimethyl sulfoxide and buffer; this mixed
      organic/aqueous approach helped alleviate issues of C60 solubility. An extensive
      set of control experiments were initially performed to verify the specific and
      ratiometric nature of QD-(pepC60)N assembly. Photoinitiated energy transfer in
      these hybrid organic-inorganic systems was then interrogated using steady-state
      and time-resolved fluorescence along with ultrafast transient absorption
      spectroscopy. Coordination of pepC60 to the QD results in QD PL quenching that
      directly tracks with the number of peptides displayed around the QD. A detailed
      photophysical analysis suggests a competition between electron transfer and
      Forster resonance energy transfer from the QD to the C60 that is dependent upon a
      complex interplay of pepC60 ratio per QD, the presence of underlying spectral
      overlap, and contributions from QD size. These results highlight several
      important factors that must be considered when designing QD-donor/C60-acceptor
      systems for potential optoelectronic and biosensing applications. 

PMID- 24128176
TI  - Tension pneumothorax, is it a really life-threatening condition?
AB  - BACKGROUND: Tension pneumothorax is a life-threatening occurrence that is
      infrequently the consequence of spontaneous pneumothorax. The aim of this study
      was to identify the risk factors for the development of tension pneumothorax and
      its effect on clinical outcomes. METHODS: We reviewed patients who were admitted
      with spontaneous pneumothorax between August 1, 2003 and December 31, 2011.
      Electronic medical records and the radiological findings were reviewed with chest
      x-ray and high-resolution computed tomography scans that were retrieved from the
      Picture Archiving Communication System. RESULTS: Out of the 370 patients included
      in this study, tension pneumothorax developed in 60 (16.2%). The bullae were
      larger in patients with tension pneumothorax than in those without (23.8 +/- 16.2
      mm vs 16.1 +/- 19.1 mm; P = 0.007). In addition, the incidence of tension
      pneumothorax increased with the lung bulla size. Fibrotic adhesion was more
      prevalent in the tension pneumothorax group than in that without (P = 0.000). The
      bullae were large in patients with fibrotic adhesion than in those without
      adhesion (35.0 +/- 22.3 mm vs 10.4 +/- 11.5 mm; P = 0.000). On multivariate
      analysis, the size of bullae (odds ratio (OR) = 1.03, P = 0.001) and fibrotic
      adhesion (OR = 10.76, P = 0.000) were risk factors of tension pneumothorax.
      Hospital mortality was 3.3% in the tension pneumothorax group and it was not
      significantly different from those patients without tension pneunothorax (P =
      0.252). CONCLUSIONS: Tension pneumothorax is not uncommon, but clinically fatal
      tension pneumothorax is extremely rare. The size of the lung bullae and fibrotic
      adhesion contributes to the development of tension pneumothorax.

PMID- 24128177
TI  - Genetics at the verge of extinction: insights from the Iberian lynx.
AB  - Population viability might become compromised by the loss of genetic diversity
      and the accumulation of inbreeding resulting from population decline and
      fragmentation. The Iberian lynx (Lynx pardinus) provides a paradigmatic example
      of a species at the verge of extinction, and because of the well-documented and
      different demographic histories of the two remaining populations (Donana and
      Andujar), it provides the opportunity to evaluate the performance of analytical
      methods commonly applied to recently declined populations. We used mitochondrial
      sequences and 36 microsatellite markers to evaluate the current genetic status of
      the species and to assess the genetic signatures of its past history.
      Mitochondrial diversity was extremely low with only two haplotypes, alternatively
      fixed in each population. Both remnant populations have low levels of genetic
      diversity at microsatellite markers, particularly the population from Donana, and
      genetic differentiation between the two populations is high. Bayesian coalescent
      based methods suggest an earlier decline starting hundreds of years ago, while
      heterozygosity excess and M-ratio tests did not provide conclusive and consistent
      evidence for recent bottlenecks. Also, a model of gene flow received overwhelming
      support over a model of pure drift. Results that are in conflict with the known
      recent demography of the species call for caution in the use of these methods,
      especially when no information on previous demographic history is available.
      Overall, our results suggest that current genetic patterns in the Iberian lynx
      are mainly the result of its recent decline and fragmentation and alerts on
      possible genetic risks for its persistence. Conservation strategies should
      explicitly consider this threat and incorporate an integrated genetic management
      of wild, captive and re-introduced populations, including genetic restoration
      through translocations. 

PMID- 24128178
TI  - When does tool use become distinctively human? Hammering in young children.
AB  - This study examines the development of hammering within an ontogenetic and
      evolutionary framework using motion-capture technology. Twenty-four right-handed
      toddlers (19-35 months) wore reflective markers while hammering a peg into a peg
      board. The study focuses on the motor characteristics that make tool use uniquely
      human: wrist involvement, lateralization, and handle use. Older children showed
      more distally controlled movements, characterized by relatively more reliance on
      the wrist, but only when hammering with their right hand. Greater age, use of the
      right hand, and more wrist involvement were associated with higher accuracy;
      handle use did not systematically change with age. Collectively, the results
      provide new insights about the emergence of hammering in young children and when
      hammering begins to manifest distinctively human characteristics.

PMID- 24128179
TI  - Value of speckle tracking for the assessment of right ventricular function in
      patients operated on for tetralogy of fallot. Comparison with magnetic resonance
      imaging.
AB  - BACKGROUND: Right ventricular (RV) function is a major prognostic factor in
      patients (pts) with operated tetralogy of Fallot (TOF). We compared the results
      of RV speckle tracking (two-dimensional [2D] strain) with those of magnetic
      resonance imaging (MRI) in this setting. METHODS: At transthoracic echocardiogram
      (echo), RV fractional area change (RVFAC), tricuspid annular plane systolic
      excursion (TAPSE), velocity of S-wave at tricuspid annulus with tissue Doppler,
      and 2D strain (longitudinal maximal systolic strain) were recorded. Their results
      were compared to RV indexed end-diastolic volume (EDV), indexed end-systolic
      volume (ESV), and RV ejection fraction (EF) at MRI. RESULTS: Twenty-two pts (16
      M) aged 11-62 years (mean 23.2 +/- 10.8) were included. Parameters of RV systolic
      function were as follows: RVFAC = 40 +/- 10%, TAPSE = 18 +/- 4 mm, S-wave = 10 +/
      0.2 cm/sec, and RV EF at MRI = 43 +/- 11%. Global RV systolic strain was -15.5
      +/- 4.2%, free wall strain was -15.1 +/- 6.3%, and septal strain was -15.8 +/-
      3.8% on average for the whole group. Echo indexed RV end-diastolic area
      correlated with EDV at MRI (r = 0.73), as well as echo indexed RV end-systolic
      area and ESV at MRI (r = 0.71). Global RV 2D strain correlated well with RV EF at
      MRI: r = 0.68; P < 0.05, and with ESV at MRI: r = 0.63. Feasibility, intra- and
      inter-observer reproducibility of 2D strain were adequate. CONCLUSIONS: Speckle
      tracking is a promising method to estimate RV systolic function in pts operated
      on for TOF.

PMID- 24128180
TI  - DNA metabarcoding multiplexing and validation of data accuracy for diet
      assessment: application to omnivorous diet.
AB  - Ecological understanding of the role of consumer-resource interactions in natural
      food webs is limited by the difficulty of accurately and efficiently determining
      the complex variety of food types animals have eaten in the field. We developed a
      method based on DNA metabarcoding multiplexing and next-generation sequencing to
      uncover different taxonomic groups of organisms from complex diet samples. We
      validated this approach on 91 faeces of a large omnivorous mammal, the brown
      bear, using DNA metabarcoding markers targeting the plant, vertebrate and
      invertebrate components of the diet. We included internal controls in the
      experiments and performed PCR replication for accuracy validation in
      postsequencing data analysis. Using our multiplexing strategy, we significantly
      simplified the experimental procedure and accurately and concurrently identified
      different prey DNA corresponding to the targeted taxonomic groups, with >= 60% of
      taxa of all diet components identified to genus/species level. The systematic
      application of internal controls and replication was a useful and simple way to
      evaluate the performance of our experimental procedure, standardize the selection
      of sequence filtering parameters for each marker data and validate the accuracy
      of the results. Our general approach can be adapted to the analysis of dietary
      samples of various predator species in different ecosystems, for a number of
      conservation and ecological applications entailing large-scale population level
      diet assessment through cost-effective screening of multiple DNA metabarcodes,
      and the detection of fine dietary variation among samples or individuals and of
      rare food items.

PMID- 24128181
TI  - Continuous flow generation and reactions of anhydrous diazomethane using a Teflon
      AF-2400 tube-in-tube reactor.
AB  - A continuous process for generation, separation, and reactions of anhydrous
      diazomethane in a tube-in-tube reactor was developed. The inner tube of the
      reactor is made of hydrophobic, gas-permeable Teflon AF-2400. The diazomethane is
      formed in the inner tube and then diffuses through the permeable membrane into
      the outer chamber and subsequently reacts in the solution carried within. This
      technique allows safe and scalable reactions with dry diazomethane to be
      performed on a laboratory scale. 

PMID- 24128183
TI  - G/U and certain wobble position mismatches as possible main causes of amino acid
      misincorporations.
AB  - A mass spectrometry-based method was developed to measure amino acid
      substitutions directly in proteins down to a level of 0.001%. When applied to
      recombinant proteins expressed in Escherichia coli, monoclonal antibodies
      expressed in mammalian cells, and human serum albumin purified from three human
      subjects, the method revealed a large number of amino acid misincorporations at
      levels of 0.001-0.1%. The detected misincorporations were not random but involved
      a single-base difference between the codons of the corresponding amino acids. The
      most frequent base differences included a change from G to A, corresponding to a
      G(mRNA)/U(tRNA) base pair mismatch during translation. We concluded that under
      balanced nutrients, G(mRNA)/U(tRNA) mismatches at any of the three codon
      positions and certain additional wobble position mismatches (C/U and/or U/U) are
      the main causes of amino acid misincorporations. The hypothesis was tested
      experimentally by monitoring the levels of misincorporation at several amino acid
      sites encoded by different codons, when a protein with the same amino acid
      sequence was expressed in E. coli using 13 different DNA sequences. The observed
      levels of misincorporation were different for different codons and agreed with
      the predicted levels. Other less frequent misincorporations may occur due to
      G(DNA)/U(mRNA) mismatch during transcription, mRNA editing, U(mRNA)/G(tRNA)
      mismatch during translation, and tRNA mischarging. 

PMID- 24128182
TI  - Cause of death in mild cognitive impairment: a prospective study (NEDICES).
AB  - BACKGROUND AND PURPOSE: Previous studies have reported the occurrence of
      increased mortality rates among individuals with mild cognitive impairment (MCI),
      but possible links between MCI subtypes and cause-specific mortality need to be
      explored. To examine short-term mortality (5 years), long-term mortality (13
      years) and cause-specific mortality of individuals over 65 years of age suffering
      from MCI compared with cognitively unimpaired individuals in the Neurological
      Disorders in Central Spain (NEDICES) cohort. METHODS: Mild cognitive impairment
      was classified using standardized psychometric and functional assessment in
      accordance with diagnostic convention. Cox's proportional hazards models,
      adjusted by sociodemographics and comorbidity factors, were used to assess the
      risk of death at 5 and 13 years of MCI subtypes compared with a reference group
      of older people without cognitive impairment (N = 2329). Causes of death were
      obtained from the National Population Register of Spain. RESULTS: There were 1484
      deceased individuals at 13 years. MCI subtypes were defined as amnestic single
      domain (N = 259), amnestic multiple domain (N = 197) and non-amnestic (N = 641).
      After adjusting for covariates, only the amnestic multiple domain MCI subtype
      showed an increased hazard ratio (HR) for mortality at 5 years versus the
      reference group. However, the HR for mortality at 13 years was increased for all
      MCI subtypes. The HR by MCI subtype was 1.19 in the non-amnestic subtype (95% CI
      1.05-1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10-1.56) and
      1.67 in the amnestic multiple domain subtype (95% CI 1.38-2.02). In terms of
      cause-specific mortality, the chance of death from dementia was statistically
      higher in all MCI subtypes. CONCLUSION: Amnestic multiple domain MCI showed the
      greatest risk of mortality in comparison with other MCI subtypes at different
      intervals. Dementia was the only cause-specific mortality that was increased in
      MCI individuals.

PMID- 24128184
TI  - More intense experiences, less intense forecasts: why people overweight
      probability specifications in affective forecasts.
AB  - We propose that affective forecasters overestimate the extent to which
      experienced hedonic responses to an outcome are influenced by the probability of
      its occurrence. The experience of an outcome (e.g., winning a gamble) is
      typically more affectively intense than the simulation of that outcome (e.g.,
      imagining winning a gamble) upon which the affective forecast for it is based. We
      suggest that, as a result, experiencers allocate a larger share of their
      attention toward the outcome (e.g., winning the gamble) and less to its
      probability specifications than do affective forecasters. Consequently, hedonic
      responses to an outcome are less sensitive to its probability specifications than
      are affective forecasts for that outcome. The results of 6 experiments provide
      support for our theory. Affective forecasters overestimated how sensitive
      experiencers would be to the probability of positive and negative outcomes
      (Experiments 1 and 2). Consistent with our attentional account, differences in
      sensitivity to probability specifications disappeared when the attention of
      forecasters was diverted from probability specifications (Experiment 3) or when
      the attention of experiencers was drawn toward probability specifications
      (Experiment 4). Finally, differences in sensitivity to probability specifications
      between forecasters and experiencers were diminished when the forecasted outcome
      was more affectively intense (Experiments 5 and 6).

PMID- 24128185
TI  - Divided we stand: three psychological regions of the United States and their
      political, economic, social, and health correlates.
AB  - There is overwhelming evidence for regional variation across the United States on
      a range of key political, economic, social, and health indicators. However, a
      substantial body of research suggests that activities in each of these domains
      are typically influenced by psychological variables, raising the possibility that
      psychological forces might be the mediating or causal factors responsible for
      regional variation in the key indicators. Thus, the present article examined
      whether configurations of psychological variables, in this case personality
      traits, can usefully be used to segment the country. Do regions emerge that can
      be defined in terms of their characteristic personality profiles? How are those
      regions distributed geographically? And are they associated with particular
      patterns of key political, economic, social, and health indicators? Results from
      cluster analyses of 5 independent samples totaling over 1.5 million individuals
      identified 3 robust psychological profiles: Friendly & Conventional, Relaxed &
      Creative, and Temperamental & Uninhibited. The psychological profiles were found
      to cluster geographically and displayed unique patterns of associations with key
      geographical indicators. The findings demonstrate the value of a geographical
      perspective in unpacking the connections between microlevel processes and
      consequential macrolevel outcomes.

PMID- 24128186
TI  - Narcissistic admiration and rivalry: disentangling the bright and dark sides of
      narcissism.
AB  - We present a process model that distinguishes 2 dimensions of narcissism:
      admiration and rivalry. We propose that narcissists' overarching goal of
      maintaining a grandiose self is pursued by 2 separate pathways, characterized by
      distinct cognitive, affective-motivational, and behavioral processes. In a set of
      7 studies, we validated this 2-dimensional model using the newly developed
      Narcissistic Admiration and Rivalry Questionnaire (NARQ). We showed that
      narcissistic admiration and rivalry are positively correlated dimensions, yet
      they have markedly different nomological networks and distinct intra- and
      interpersonal consequences. The NARQ showed the hypothesized 2-dimensional
      multifaceted structure as well as very good internal consistencies (Study 1, N =
      953), stabilities (Study 2, N = 93), and self-other agreements (Study 3, N = 96).
      Narcissistic admiration and rivalry showed unique relations to the Narcissistic
      Personality Inventory (NPI), the Big Five, self-esteem, pathological narcissism,
      and other narcissism-related traits like Machiavellianism, psychopathy, self
      enhancement, and impulsivity (Study 4, Ns = 510-1,814). Despite the positive
      relation between admiration and rivalry, the 2 differentially predicted general
      interpersonal orientations and reactions to transgressions in friendships and
      romantic relationships (Study 5, N = 1,085), interpersonal perceptions during
      group interactions (Study 6, N = 202), and observed behaviors in experimental
      observations (Study 7, N = 96). For all studies, the NARQ outperformed the
      standard measure of narcissism, the NPI, in predicting outcome measures. Results
      underscore the utility of a 2-dimensional conceptualization and measurement of
      narcissism.

PMID- 24128187
TI  - Settling for less out of fear of being single.
AB  - The present research demonstrates that fear of being single predicts settling for
      less in romantic relationships, even accounting for constructs typically examined
      in relationship research such as anxious attachment. Study 1 explored the content
      of people's thoughts about being single. Studies 2A and 2B involved the
      development and validation of the Fear of Being Single Scale. Study 2C provided
      preliminary support for the hypothesis that fear of being single predicts
      settling for less in ongoing relationships, as evidenced by greater dependence in
      unsatisfying relationships. Study 3 replicated this effect in a longitudinal
      study demonstrating that fear of being single predicts lower likelihood of
      initiating the dissolution of a less satisfying relationship. Studies 4A and 4B
      explored the predictive ability of fear of being single for self-reported dating
      standards. Across both samples, fear of being single was unrelated to self
      reported standards for a mate, with the exception of consistently higher
      standards for parenting. Studies 5 and 6 explored romantic interest in targets
      that were manipulated to vary in responsiveness and physical attractiveness.
      These studies found that fear of being single consistently predicted romantic
      interest in less responsive and less attractive dating targets. Study 7 explored
      fear of being single during a speed-dating event. We found that fear of being
      single predicted being less selective in expressing romantic interest but did not
      predict other daters' romantic interest. Taken together, the present research
      suggests that fear of being single is a meaningful predictor of settling for less
      in relationships.

PMID- 24128188
TI  - Sex differences in the implications of partner physical attractiveness for the
      trajectory of marital satisfaction.
AB  - Do men value physical attractiveness in a mate more than women? Scientists in
      numerous disciplines believe that they do, but recent research using speed-dating
      paradigms suggests that males and females are equally influenced by physical
      attractiveness when choosing potential mates. Nevertheless, the premise of the
      current work is that sex differences in the importance of physical attractiveness
      are most likely to emerge in research on long-term relationships. Accordingly,
      the current work drew from 4 independent, longitudinal studies to examine sex
      differences in the implications of partner physical attractiveness for
      trajectories of marital satisfaction. In all 4 studies, both partners' physical
      attractiveness was objectively rated at baseline, and both partners reported
      their marital satisfaction up to 8 times over the first 4 years of marriage.
      Whereas husbands were more satisfied at the beginning of the marriage and
      remained more satisfied over the next 4 years to the extent that they had an
      attractive wife, wives were no more or less satisfied initially or over the next
      4 years to the extent that they had an attractive husband. Most importantly, a
      direct test indicated that partner physical attractiveness played a larger role
      in predicting husbands' satisfaction than predicting wives' satisfaction. These
      findings strengthen support for the idea that sex differences in self-reported
      preferences for physical attractiveness do have implications for long-term
      relationship outcomes.

PMID- 24128189
TI  - Expression of a type 2 diacylglycerol acyltransferase from Thalassiosira
      pseudonana in yeast leads to incorporation of docosahexaenoic acid beta-oxidation
      intermediates into triacylglycerol.
AB  - Glycerolipids of the marine diatom Thalassiosira pseudonana are enriched
      particularly with eicosapentaenoic acid (EPA), and also with an appreciable level
      of docosahexaenoic acid (DHA). The present study describes the functional
      characterization of a type 2 diacylglycerol acyltransferase (DGAT2, EC 2.3.1.20)
      from T. pseudonana, designated TpDGAT2, which catalyzes the final step of
      triacylglycerol (TAG) synthesis. Heterologous expression of this gene restored
      TAG formation in a yeast mutant devoid of TAG biosynthesis. TpDGAT2 was also
      shown to exert a large impact on the fatty acid profile of TAG. Its expression
      caused a 10-12% increase of 18:1 and a concomitant decrease of 16:0 relative to
      that of AtDGAT1(Arabidopsis thaliana). Furthermore, in the presence of the very
      long-chain polyunsaturated fatty acids (VLCPUFA) EPA and DHA, TAG formed by
      TpDGAT2 displayed three- to six-fold increases in the percentage of VLCPUFA
      relative to that of AtDGAT1 even though TpDGAT2 conferred much lower TAG
      synthetic activities than Arabidopsis DGAT1. Strikingly, when fed DHA, the yeast
      mutant expressing TpDGAT2 incorporated high levels of EPA and DHA isomers derived
      from DHA beta-oxidation. In contrast, no such phenomenon occurred in the cells
      expressing AtDGAT1. These results suggested that, in addition to the role in
      breaking down storage lipids, yeast peroxisomes also contribute to lipid
      synthesis by recycling acyl-CoAs when a fatty acyl assembly system is available
      to capture and utilize the fatty acyl pools generated via beta-oxidation. Our
      study hence illustrated a case where the efficiency and substrate preference of
      an acyltransferase can elicit far reaching metabolic adjustments that affect TAG
      composition.

PMID- 24128190
TI  - Newborn screening policy and practice issues for nurses.

PMID- 24128191
TI  - Mood and objective and subjective measures of sleep during late pregnancy and the
      postpartum period.
AB  - This study examined the association between measures of objective sleep (OS) and
      subjective sleep (SS) to postpartum mood in healthy women from the third
      trimester of pregnancy to 10 to 12 weeks postpartum. Twenty-nine pregnant women
      completed self-report measures of mood and SS, and wore actigraphs for 7
      continuous days during the third trimester (Time 1), within 15 days (Time 2), and
      10 to 12 weeks postpartum (Time 3). The subjective perception of marked daytime
      dysfunction was associated with low mood during Time 1 and Time 3. Poor nighttime
      SS was related to low mood only at Time 2, whereas poor nighttime OS influenced
      stress during the same assessment time. These data indicate a stronger
      association between postpartum mood and the subjective perception of sleep than
      with OS quality and duration in healthy, non-depressed women, and highlight the
      awareness of poor daytime functioning as a significant contributor to new
      mothers' emotional wellbeing. 

PMID- 24128193
TI  - Difficulties and barriers in diagnosing Fabry disease: what can be learnt from
      the literature?
AB  - INTRODUCTION: Fabry disease (FD) is an X-linked disorder of glycosphingolipid
      metabolism caused by deficiency of the lysosomal enzyme alpha galactosidase A.
      Clinical features include neuropathic pain, rash, proteinuria renal failure,
      stroke and cardiomyopathy accompanied by a reduced life expectancy. Patients
      report an average delay of > 10 years between symptom onset and diagnosis.
      Newborn screening studies suggest a much higher prevalence than that found on
      population studies supporting the notion that FD is under-diagnosed. AREAS
      COVERED: Four key challenges in the diagnosis of FD and strategies to overcome
      them are discussed. The clinical features of FD are highly heterogeneous
      resulting in patients presenting to many different specialists, often with non
      specific symptoms with a wide differential diagnosis. The pathophysiological
      mechanisms underlying this are poorly understood and the prediction of
      pathogenicity on the basis of gene mutation analysis can be problematic. While
      the availability of treatment adds an impetus to make the correct diagnosis, our
      understanding of when and if treatment may be required in a specific individual
      is incomplete. EXPERT OPINION: Improving diagnostic rates of FD requires a
      greater awareness of the disorder among physicians to whom patients may present,
      new strategies to determine the pathogenicity of novel mutations and a greater
      understanding of the natural history of FD across the phenotypic spectrum.
      Collaborative clinical and laboratory research is vital in furthering knowledge
      of the underlying mechanisms of this disorder and how they may be impacted by
      current or future therapies.

PMID- 24128194
TI  - Effects of butorphanol versus dexmedetomidine sedation on intradermal allergen
      and histamine responses in dogs with atopic dermatitis.
AB  - BACKGROUND: Sedation is commonly used during intradermal testing (IDT). Morphine
      and its derivatives have long been avoided because of their histamine-releasing
      effects. HYPOTHESIS/OBJECTIVES: Butorphanol, an opioid agonist/antagonist, will
      not adversely affect IDT in dogs. ANIMALS: Ten client-owned dogs diagnosed with
      atopic dermatitis. METHODS: Dogs were randomized to be sedated with butorphanol
      (0.4 mg/kg) or dexmedetomidine (5 MUg/kg). Routine IDT along with intradermal
      injections of various dilutions of histamine were performed on the lateral
      thorax, followed 7 days later by the alternative sedative and IDT on the opposite
      side. The injection sites were subjectively scored and objectively measured by
      one investigator, blinded to the sedatives, and compared between groups. RESULTS:
      When the mean wheal diameters from the objective measurements of all antigens,
      including saline and histamine dilutions, were compared, butorphanol was
      associated with significantly smaller reactions than dexmedetomidine (P =
      0.0001). There was a high level of agreement between sedatives when positive
      reactions subjectively scored as >=3+ were compared (kappa = 0.91). When mean
      wheal diameters of histamine at concentrations of 1:100,000, 1:400,000,
      1:1,600,000 and 1:6,400,000 were compared, there were no significant differences
      between sedative types. Moreover, the percentage agreement when comparing
      subjective interpretation of all histamine dilutions between sedations was high
      (kappa = 0.90). However, there was only 69% agreement beyond chance when
      objective and subjective interpretations of all antigens were compared between
      sedative groups. CONCLUSIONS: Although butorphanol resulted in significantly
      smaller wheal size in comparison to dexmedetomidine, it did not affect the
      overall subjective interpretation of the results of IDT.

PMID- 24128195
TI  - Morningness-eveningness and treatment response in major depressive disorder.
AB  - In a large, prospective, 8-week open study of 721 outpatients receiving
      agomelatine treatment for a current major depressive episode (MDE), morningness
      eveningness (Composite Scale of Morningness) was assessed before and after
      treatment to investigate possible changes in morningness-eveningness after
      treatment and evaluate whether morningness-eveningness at baseline predicted
      treatment response. A change towards morningness was observed after treatment.
      This change was greater in responders than non-responders. Moreover, being a
      morning type at baseline was an independent predictor of response to treatment.
      Once thought to be a trait variable, morningness-eveningness is a potential
      treatment target that should be systematically assessed in MDE patients. 

PMID- 24128196
TI  - Moderation of genetic and environmental influences on diurnal preference by age
      in adult twins.
AB  - Diurnal preference changes across the lifespan. However, the mechanisms
      underlying this age-related shift are poorly understood. The aim of this twin
      study was to determine the extent to which genetic and environmental influences
      on diurnal preference are moderated by age. Seven hundred and sixty-eight
      monozygotic and 674 dizygotic adult twin pairs participating in the University of
      Washington Twin Registry completed the reduced Morningness-Eveningness
      Questionnaire as a measure of diurnal preference. Participants ranged in age from
      19 to 93 years (mean = 36.23, SD = 15.54) and were categorized on the basis of
      age into three groups: younger adulthood (19-35 years, n = 1715 individuals),
      middle adulthood (36-64 years, n = 1003 individuals) and older adulthood (65+
      years, n = 168 individuals). Increasing age was associated with an increasing
      tendency towards morningness (r = 0.42, p < 0.001). Structural equation modeling
      techniques parsed the variance in diurnal preference into genetic and
      environmental influences for the total sample as well as for each age group
      separately. Additive genetic influences accounted for 52%[46-57%], and non-shared
      environmental influences 48%[43-54%], of the total variance in diurnal
      preference. In comparing univariate genetic models between age groups, the best
      fitting model was one in which the parameter estimates for younger adults and
      older adults were equated, in comparison with middle adulthood. For younger and
      older adulthood, additive genetic influences accounted for 44%[31-49%] and non
      shared environmental influences 56%[49-64%] of variance in diurnal preference,
      whereas for middle adulthood these estimates were 34%[21-45%] and 66%[55-79%],
      respectively. Therefore, genetic influences on diurnal preference are attenuated
      in middle adulthood. Attenuation is likely driven by the increased importance of
      work and family responsibilities during this life stage, in comparison with
      younger and older adulthood when these factors may be less influential in
      determining sleep-wake timing. These findings have implications for studies aimed
      at identifying specific non-shared environmental influences, as well as molecular
      genetic studies aimed at identifying specific polymorphisms associated with
      diurnal preference. 

PMID- 24128198
TI  - Habitat-former effects on prey behaviour increase predation and non-predation
      mortality.
AB  - Habitat-forming species can influence mortality on associated species via
      altering structural and non-structural abiotic conditions. Importantly, these
      effects can occur simultaneously and in opposite directions, although how they
      contribute to the net outcomes for predator-prey interactions remain unexplored.
      Seagrasses often have positive effects on associated fauna because their
      structure directly reduces predator encounter rates. However, we identified a
      'risky' behaviour (shallower burial) in an infaunal bivalve at a high seagrass
      cover--likely induced by non-structural abiotic change--suggesting positive
      effects may be outweighed by risky behaviours. We determined whether the physical
      structure of the seagrass interacted with burial behaviour of clams to determine
      the predation and non-predation mortality and whether these interactions were
      mediated by the cover of the seagrass. Surveys on an intertidal sand flat in
      Tasmania, Australia showed that the highest densities of a dominant bivalve,
      Katelysia scalarina, occurred at low (33%) seagrass cover, but the lowest
      densities and the highest proportion of unburied clams occurred at high (100%)
      cover. A field experiment manipulating burial depth, seagrass cover and predator
      access demonstrated that unburied clams suffered very high predation and non
      predation mortality compared to buried clams (~4x higher), which outweighed any
      positive effects of the seagrass structure in reducing predator access. Being
      unburied also had non-lethal consequences with surviving unburied clams having a
      reduced tissue biomass compared to buried clams. In this system, predation was
      driven by the availability of prey when they undertake a risky behaviour (shallow
      burial). However, significant changes in behaviour may only occur once a
      threshold of habitat-former density is reached. In this instance, changes in
      behaviour were likely due to seagrass effects on sediment redox potential, which
      decreased significantly above 33% seagrass cover. Our findings demonstrate that
      the negative effects of a habitat-former on the behaviour of associated species,
      via alteration of non-structural abiotic conditions, can outweigh any positive
      effects provided by increasing habitat structure as is commonly reported for
      habitat-formers.

PMID- 24128197
TI  - NMR investigation of the role of osteocalcin and osteopontin at the organic
      inorganic interface in bone.
AB  - Mechanical resilience of bone tissue decreases with age. The ability to
      comprehensively probe and understand bone properties could help alleviate this
      problem. One important aspect of bone quality that has recently been made evident
      is the presence of dilatational bands formed by osteocalcin (OC) and osteopontin
      (OPN), which contribute to fracture toughness. However, experimental evidence of
      the structural role of these two proteins at the organic-mineral interface in
      bone is still needed. Solid state nuclear magnetic resonance (SSNMR) is emerging
      as a useful technique in probing molecular level aspects of bone. Here, we
      present the first SSNMR study of bone tissue from genetically modified mice
      lacking OC and/or OPN. Probing the mineral phase, the organic matrix and their
      interface revealed that, despite the absence of OC and OPN, the organic matrix
      and mineral were well preserved, and the overall exposure of collagen to
      hydroxyapatite (HA) nanoparticles was hardly affected. However, the proximity to
      the HA surface was slightly increased for a number of bone components including
      less abundant amino acids like lysine, suggesting that this is how the tissue
      compensates for the lack of OC and OPN. Taken together, the NMR data supports the
      recently proposed model, in which the contribution of OC-OPN to fracture
      toughness is related to their presence at the extrafibrillar organic-mineral
      interfaces, where they reinforce the network of mineralized fibrils and form
      dilatational bands. In an effort toward further understanding the structural role
      of individual amino acids of low abundance in bone, we then explored the
      possibility of specific (13)C enrichment of mouse bone, and report the first
      SSNMR spectra of 97% (13)C lysine-enriched tissue. Results show that such
      isotopic enrichment allows valuable molecular-level structural information to be
      extracted, and sheds light on post-translational modifications undergone by
      specific amino acids in vivo. 

PMID- 24128199
TI  - Coexistence of linear morphea and nodular mucinosis.

PMID- 24128200
TI  - A simple equation: safe staffing equals safe care.
AB  - Dozens of campaigners including MPs attended a parliamentary reception co-hosted
      by Nursing Standard last week on behalf of the Safe Staffing Alliance, the expert
      group set up as part of our Care campaign. Everyone was keen to associate
      themselves with an organisation that has highlighted the importance of employing
      the right number and mix of staff in all healthcare settings. 

PMID- 24128201
TI  - Senior nurses convince MPs to back campaign for safe staffing.
AB  - Members of the Commons health committee were among MPs and peers who signed up to
      a campaign on safe staffing levels at a high-profile event held by senior nurses
      in the Houses of Parliament last week. 

PMID- 24128207
TI  - Unions to fight DH's call for another pay freeze.
AB  - Nursing unions are braced for a battle with the Department of Health following
      its calls to curb pay increases for nurses and other NHS staff. 

PMID- 24128208
TI  - Quality of NHS care has remained high, despite financial pressures.
AB  - Healthcare associated infection rates have dropped, cancer patients receive
      treatment quicker and hip fracture patients have lower mortality rates, but
      greater focus is needed on preventing emergency admissions, according to an
      analysis of NHS care. 

PMID- 24128214
TI  - Don't wait to report child abuse, implores leading academic.
AB  - All nurses have a professional and personal duty to safeguard children, an
      eminent nurse in the field of child protection said last week. 

PMID- 24128216
TI  - MP expresses disbelief at inability of NMC to accept fees in instalments.
AB  - The Nursing and Midwifery Council was reprimanded by an influential group of MPs
      last week over its failure to introduce a system that would allow nurses and
      midwives to pay their annual L100 registration fee in instalments. 

PMID- 24128218
TI  - Transgressing the code - why fitness to practise is an undergraduate issue.
AB  - More than 800 nursing students have been subject to disciplinary proceedings by
      their universities in the past three years, Nursing Standard can reveal. 

PMID- 24128224
TI  - Headaches.

PMID- 24128225
TI  - Rate my care.
AB  - The Friends and Family Test asks patients on hospitals wards and in emergency
      departments to indicate whether they would recommend the service to their loved
      ones. Critics says the test is flawed and its results are distorted, while others
      argue that it produces useful feedback.

PMID- 24128227
TI  - Triumph of the trolley.
AB  - Concerned about knee and back injuries, community nurse Linda Harris designed a
      footbath trolley that allows her to care for patients with leg ulcers without
      putting herself at risk. Thanks to the height-adjustable trolley, she no longer
      has to kneel on the floor to wash patients' feet at her leg ulcer clinic.

PMID- 24128226
TI  - Who pays for the pastor?

PMID- 24128234
TI  - Starting out - a patient derived great comfort from the spiritual care I
      provided.
AB  - While I was working a shift in a care home as part of a five-week clinical
      placement, one of the residents became concerned that his failing memory was
      causing him to forget the words to the Lord's Prayer. 

PMID- 24128240
TI  - No pay rise, no holiday bonus - how can we balance work and home life?

PMID- 24128241
TI  - The government is treating us as if we were the enemy within.

PMID- 24128242
TI  - What sort of future do the best and brightest have in nursing?

PMID- 24128243
TI  - Carrot and stick - Whitehall's dual approach to flu-jab uptake.

PMID- 24128245
TI  - Practice nursing is the way to go for masters of many trades.

PMID- 24128246
TI  - Cultural change must accompany technological advancement.

PMID- 24128247
TI  - I did not intend to demean hospice at home professionals.

PMID- 24128248
TI  - Understanding grounded theory.
AB  - Grounded theory is a systematic research approach involving the discovery of
      theory through data collection and analysis. In particular, the focus is on
      uncovering patterns in social life that individuals might or might not be aware
      of. This article provides a practical overview of grounded theory to guide the
      research process in this area. The article is aimed at the nurse researcher who
      has some knowledge of grounded theory and/or is considering using this method of
      inquiry. 

PMID- 24128249
TI  - Non-pharmacological treatments for patients with depression.
AB  - Depression is a common mental health disorder. People with physical health
      problems are at increased risk of depression, which adversely affects quality of
      life, worsens disabilities and is associated with increased mortality. Several
      treatments are available for people with depression, and these are commonly
      delivered using a stepped-care or matched and stepped-care model. Structured self
      help and guided self-help interventions should be offered when depression is
      diagnosed. If these treatments are not effective, high-intensity interventions
      such as face-to-face talking therapies should be offered. Nurses have many
      existing competencies with which to recognise depression and can treat depression
      with additional training and supervision. 

PMID- 24128250
TI  - Late stage dementia.

PMID- 24128251
TI  - Prevention and management of neuropathic diabetic foot ulcers.
AB  - Peripheral neuropathy is a common complication of diabetes that can reduce
      patients' quality of life, and is a major risk factor for foot ulceration and
      limb amputation. This article outlines the aetiological and pathological factors
      involved in the development of diabetic foot ulceration through the use of a case
      study. The role of diabetes foot screening is explored as a preventive measure,
      and the importance of risk assessment and stratification, and appropriate
      referral are discussed. 

PMID- 24128252
TI  - The role of nutrition in preventing pressure ulcers.
AB  - Old age, pressure ulcers and malnutrition may co-exist. Wounds in older people
      may already be slow to heal as a result of compromised skin integrity, which
      occurs as part of the normal ageing process. Malnutrition is also more common in
      older people, and evidence has shown that inadequate nutrition may lead to
      impaired and prolonged wound healing. This article explores the relationship
      between nutrition and wound healing, and promotes optimum nutrition in old age as
      an essential component of effective wound management. 

PMID- 24128253
TI  - Route to satisfaction.
AB  - Getting your dream job begins with introspection, according to John Lees, author
      of How to Get a Job You'll Love. 'The starting point is understanding yourself
      better,' he says. 'Think about the things you like to do, the kinds of people you
      like to be around. Review your experience. What did you enjoy most? What do you
      find memorable?' 

PMID- 24128254
TI  - Bridge of knowledge.
AB  - Link nurses are a bridge between specialist and general nurses, nurturing
      relationships and bringing knowledge from their specialist colleagues to
      encourage good specialist practice in general care environments. 

PMID- 24128256
TI  - Think you could do a PhD?
AB  - Talking to my researcher colleagues has shown me that the main motivation for
      nurses to undertake a doctorate is a belief that evidence-based practice is so
      important that nurses should dedicate time to it. 

PMID- 24128257
TI  - Student life - compassionate to the core.
AB  - Earlier this year, journalist Christina Patterson spoke to 200 nursing students
      and staff from the BSc Nursing programme at the University of York and asked:
      'How do nurses keep compassion alive?' 

PMID- 24128258
TI  - Two distinct sensing pathways allow recognition of Klebsiella pneumoniae by
      Dictyostelium amoebae.
AB  - Recognition of bacteria by metazoans is mediated by receptors that recognize
      different types of microorganisms and elicit specific cellular responses. The
      soil amoebae Dictyostelium discoideum feeds upon a variable mixture of
      environmental bacteria, and it is expected to recognize and adapt to various food
      sources. To date, however, no bacteria-sensing mechanisms have been described. In
      this study, we isolated a Dictyostelium mutant (fspA KO) unable to grow in the
      presence of non-capsulated Klebsiella pneumoniae bacteria, but growing as
      efficiently as wild-type cells in the presence of other bacteria, such as
      Bacillus subtilis. fspA KO cells were also unable to respond to K. pneumoniae and
      more specifically to bacterially secreted folate in a chemokinetic assay, while
      they responded readily to B. subtilis. Remarkably, both WT and fspA KO cells were
      able to grow in the presence of capsulated LM21 K. pneumoniae, and responded to
      purified capsule, indicating that capsule recognition may represent an
      alternative, FspA-independent mechanism for K. pneumoniae sensing. When LM21
      capsule synthesis genes were deleted, growth and chemokinetic response were lost
      for fspA KO cells, but not for WT cells. Altogether, these results indicate that
      Dictyostelium amoebae use specific recognition mechanisms to respond to different
      K. pneumoniae elements. 

PMID- 24128259
TI  - Fire-induced population reduction and landscape opening increases gene flow via
      pollen dispersal in Pinus halepensis.
AB  - Population reduction and disturbances may alter dispersal, mating patterns and
      gene flow. Rather than taking the common approach of comparing different
      populations or sites, here we studied gene flow via wind-mediated effective
      pollen dispersal on the same plant individuals before and after a fire-induced
      population drop, in a natural stand of Pinus halepensis. The fire killed 96% of
      the pine trees in the stand and cleared the vegetation in the area. Thirteen
      trees survived in two groups separated by ~80 m, and seven of these trees had
      serotinous (closed) prefire cones that did not open despite the fire. We analysed
      pollen from closed pre and postfire cones using microsatellites. The two groups
      of surviving trees were highly genetically differentiated, and the pollen they
      produced also showed strong among-group differentiation and very high kinship
      both before and after the fire, indicating limited and very local pollen
      dispersal. The pollen not produced by the survivors also showed significant
      prefire spatial genetic structure and high kinship, indicating mainly within
      population origin and limited gene flow from outside, but became spatially
      homogeneous with random kinship after the fire. We suggest that postfire gene
      flow via wind-mediated pollen dispersal increased by two putative mechanisms: (i)
      a drastic reduction in local pollen production due to population thinning,
      effectively increasing pollen immigration through reduced dilution effect; (ii)
      an increase in wind speeds in the vegetation-free postfire landscape. This
      research shows that dispersal can alleviate negative genetic effects of
      population size reduction and that disturbances might enhance gene flow, rather
      than reduce it.

PMID- 24128262
TI  - Systems medicine: opportunities and challenges for systems biology approaches.
AB  - Technological advance have not only dramatically accelerated progress in medical
      knowledge and practice, but also revealed the enormous complexity of diseases and
      pathogenetic mechanisms. Can systems biology approaches and computational
      modelling help defeat the challenge of exploding complexity? Four review articles
      discuss the challenges and opportunities for such systems level approaches in
      medicine, pathology and drug development. 

PMID- 24128261
TI  - Using random walks to identify cancer-associated modules in expression data.
AB  - BACKGROUND: The etiology of cancer involves a complex series of genetic and
      environmental conditions. To better represent and study the intricate genetics of
      cancer onset and progression, we construct a network of biological interactions
      to search for groups of genes that compose cancer-related modules. Three cancer
      expression datasets are investigated to prioritize genes and interactions
      associated with cancer outcomes. Using a graph-based approach to search for
      communities of phenotype-related genes in microarray data, we find modules of
      genes associated with cancer phenotypes in a weighted interaction network.
      RESULTS: We implement Walktrap, a random-walk-based community detection
      algorithm, to identify biological modules predisposing to tumor growth in 22
      hepatocellular carcinoma samples (GSE14520), adenoma development in 32 colorectal
      cancer samples (GSE8671), and prognosis in 198 breast cancer patients (GSE7390).
      For each study, we find the best scoring partitions under a maximum cluster size
      of 200 nodes. Significant modules highlight groups of genes that are functionally
      related to cancer and show promise as therapeutic targets; these include
      interactions among transcription factors (SPIB, RPS6KA2 and RPS6KA6), cell-cycle
      regulatory genes (BRSK1, WEE1 and CDC25C), modulators of the cell-cycle and
      proliferation (CBLC and IRS2) and genes that regulate and participate in the map
      kinase pathway (MAPK9, DUSP1, DUSP9, RIPK2). To assess the performance of
      Walktrap to find genomic modules (Walktrap-GM), we evaluate our results against
      other tools recently developed to discover disease modules in biological
      networks. Compared with other highly cited module-finding tools, jActiveModules
      and Matisse, Walktrap-GM shows strong performance in the discovery of modules
      enriched with known cancer genes. CONCLUSIONS: These results demonstrate that the
      Walktrap-GM algorithm identifies modules significantly enriched with cancer
      genes, their joint effects and promising candidate genes. The approach performs
      well when evaluated against similar tools and smaller overall module size allows
      for more specific functional annotation and facilitates the interpretation of
      these modules.

PMID- 24128260
TI  - Behind the wheel and on the map: Genetic and environmental associations between
      drunk driving and other externalizing behaviors.
AB  - Drunk driving, a major contributor to alcohol-related mortality, has been linked
      to a variety of other alcohol-related (e.g., Alcohol Dependence, early age at
      first drink) and non-alcohol-related externalizing behaviors. In a sample of 517
      same-sex twin pairs from the National Longitudinal Study of Adolescent Health, we
      examined 3 conceptualizations of the etiology of drunk driving in relation to
      other externalizing behaviors. A series of behavioral-genetic models found
      consistent evidence for drunk driving as a manifestation of genetic
      vulnerabilities toward a spectrum of alcohol-related and non-alcohol-related
      externalizing behaviors. Most notably, multidimensional scaling analyses produced
      a genetic "map" with drunk driving located near its center, supporting the
      strength of drunk driving's genetic relations with a broad range of externalizing
      behaviors. In contrast, nonshared environmental associations with drunk driving
      were weaker and more diffuse. Drunk driving may be a manifestation of genetic
      vulnerabilities toward a broad externalizing spectrum.

PMID- 24128263
TI  - Health systems innovation: addressing the dynamics of multilayered 'complex
      bundles' of knowledge.

PMID- 24128264
TI  - Development of an Arabis alpina genomic contig sequence data set and application
      to single nucleotide polymorphisms discovery.
AB  - The alpine plant Arabis alpina is an emerging model in the ecological genomic
      field which is well suited to identifying the genes involved in local adaptation
      in contrasted environmental conditions, a subject which remains poorly understood
      at molecular level. This study presents the assembly of a pool of A. alpina
      genomic fragments using next-generation sequencing technologies. These contigs
      cover 172 Mb of the A. alpina genome (i.e. 50% of the genome) and were shown to
      contain sequences giving positive hits against 96% of the 458 CEGMA core genes
      (Core Eukaryotic Genes Mapping Approach), a set of highly conserved eukaryotic
      genes. Regions presenting high nucleic sequence identity with 77% of the close
      relative Arabidopsis thaliana's genes were found with an unbiased distribution
      across the different functional categories of A. thaliana genes. This new
      resource was tested using a resequencing assay to identify polymorphic sites.
      Sixteen samples were successfully analysed and 127,041 single-nucleotide
      polymorphisms identified. This contig data set will contribute to improving our
      understanding of the ecology of Arabis alpina, thus constituting an important
      resource for future ecological genomic studies.

PMID- 24128265
TI  - Positive vascular wall margins have minimal impact on cancer outcomes in patients
      with non-metastatic renal cell carcinoma (RCC) with tumour thrombus.
AB  - OBJECTIVE: To evaluate the impact of microscopically positive vascular margins on
      recurrence and cancer-specific survival (CSS) in patients with renal cell
      carcinoma (RCC) with venous thrombus PATIENTS AND METHODS: We reviewed the
      records from the period 1993 to 2009 of consecutive patients treated surgically
      for RCC with venous tumour thrombus at the University of Texas MD Anderson Cancer
      Center. Patients with metastatic disease, positive soft tissue margins or gross
      residual disease at time of thrombectomy were excluded. The primary outcome
      measures were local or systemic disease recurrence, and CSS. Univariate and
      multivariate analysis were used to evaluate whether microscopically positive
      vascular margins were associated with RCC recurrence or CSS after nephrectomy
      with thrombectomy. RESULTS: A total of 256 patients with RCC were identified with
      a median (interquartile range) follow-up of 36.7 (18.4-63.5) months. Microscopic
      tumour was present at the margin of resection in 47 patients (18.4%). The median
      recurrence-free interval was significantly shorter in patients with positive
      vascular margins: 22.1 vs 70.2 months (P = 0.009). The rate of local recurrence
      was higher in patients with positive vein margins: 12.8 vs 4.3% (P < 0.01). Local
      recurrence without concomitant systemic recurrence was identified in only two of
      256 (0.8%) patients. Patients with positive vascular margins had significantly
      worse CSS times compared with patients with negative vascular margins: 37.7 vs
      93.0 months (P = 0.004). In multivariable analysis, positive vascular margins
      were found to be independently predictive of local recurrence but not of systemic
      recurrence or CSS. CONCLUSIONS: Complete surgical excision should always be
      attempted because positive vascular wall margins increase local recurrence rates.
      Invasion of RCC into the vein wall at the resection margin is associated with
      aggressive tumour biology, and the majority of patients with positive vascular
      wall margins experience systemic recurrence.

PMID- 24128266
TI  - Evidence-based medicine: the design and interpretation of noninferiority clinical
      trials in veterinary medicine.
AB  - Noninferiority trials are clinical studies designed to demonstrate that an
      investigational drug is at least as effective as an established treatment within
      a predetermined margin. They are conducted, in part, because of ethical concerns
      of administering a placebo to veterinary patients when an established effective
      treatment exists. The use of noninferiority trial designs has become more common
      in veterinary medicine with the increasing number of established veterinary
      therapeutics and the desire to eliminate potential pain or distress in a placebo
      controlled study. Selecting the appropriate active control and an a priori
      noninferiority margin between the investigational and active control drug are
      unique and critical design factors for noninferiority studies. Without reliable
      historical knowledge of the disease response in the absence of treatment and of
      the response to the selected active control drug, proper design and
      interpretation of a noninferiority trial is not possible. Despite the appeal of
      conducting noninferiority trials to eliminate ethical concerns of placebo
      controlled studies, there are real limitations and possible ethical conundrums
      associated with noninferiority trials. The consequences of incorrect study
      conclusions because of poor noninferiority trial design need careful attention.
      Alternative trial designs to typical noninferiority studies exist, but these too
      have limitations and must also be carefully considered. 

PMID- 24128267
TI  - Predictive validity of social support relative to psychological well-being in men
      with spinal cord injury.
AB  - PURPOSE: Compare predictive validity (relative to psychological well-being) of
      long and short versions of 2 measures of social support for persons with spinal
      cord injury (SCI). RESEARCH METHOD: Sixty-nine men with SCI completed (a) a long
      and short version of the Interpersonal Support Evaluation List (ISEL), (b) a
      structured interview regarding the frequency with which a person receives 11
      kinds of support from each of their most important supporters (maximum of 5), and
      (c) a global measure of the same 11 kinds of support. Approximately 3 years later
      they completed 4 measures of psychological well-being--the Center for
      Epidemiologic Studies Depression scale (CESD), the Life Satisfaction Index A
      (LSIA), the Perceived Stress Scale (PSS), and the Rosenberg Self-Esteem Scale
      (RSES). Comparisons were made among the social support measures with regard to
      their ability to predict each of the 4 measures of psychological well-being at a
      later point in time. RESULTS: The long version of the ISEL had more predictive
      power than the long version of the structured interview. CONCLUSIONS: The long
      version of the ISEL is a good choice for measuring social support in persons with
      SCI and the short ISEL may be an acceptable choice when minimizing respondent
      burden is critical if the number of response options is increased to 4.

PMID- 24128268
TI  - Dimensions of coping in chronic pain patients: factor analysis and cross
      validation of the German version of the Coping Strategies Questionnaire (CSQ-D).
AB  - PURPOSE: The Coping Strategies Questionnaire (CSQ) by Rosenstiel and Keefe (1983)
      is one of the most widely used measures of coping strategies in pain patients,
      although its construct and factorial validity is dissatisfying. Verra, Angst,
      Lehmann, and Aeschlimann (2006) translated the full measure, which assesses eight
      different coping strategies, into German (CSQ-D). Our aim was to identify stable
      latent dimensions and present a shorter and more valid version of the CSQ-D.
      METHODS: A principal axes factor analysis (PFA) and a confirmatory factor
      analysis (CFA) were performed for specification and cross-validation of the new
      model. Thus, two independent samples of patients with fibromyalgia-like symptoms
      (n = 321, n = 162) completed questionnaire batteries that included the CSQ-D and
      measures of fibromyalgia (FM) impact, pain, depression, and anxiety. RESULTS: The
      most interpretable result appeared to be a six-factor model with an acceptable
      fit. The first four factors, (1) Catastrophizing, (2) Ignoring Pain, (3)
      Diversion, and (4) Reinterpreting Pain, resemble the original scales by
      Rosenstiel and Keefe (1983). The Praying or Hoping scale split up into distinct
      (5) Praying and (6) Hoping dimensions. Except Praying, all coping strategies were
      significantly associated with measures of psychological health outcomes, pain,
      overall FM impact, or social support. CONCLUSIONS: The new short form, called CSQ
      DS, is a valid and reliable instrument, composed of 26 items and assessing six
      coping strategies. Future investigations are recommended to further prove both
      the external and construct validity of the CSQ-DS.

PMID- 24128269
TI  - Accessing crisis intervention services after brain injury: a mixed methods study.
AB  - PURPOSE: To understand empirically the perceived barriers to accessing crisis
      intervention services for individuals with acquired brain injury. METHOD: This
      action research design encompassed two phases of mixed methods data collection
      and analysis. Phase one consisted of the electronic distribution of a survey
      comprised primarily of quantitative items, launched to a nonrandom sample of 226
      providers with a response rate of 49% (n = 110). Phase two entailed seven focus
      group interviews with 25 participants, designed to add explanatory power to phase
      one results. RESULTS: Quantitative results revealed an array of major barriers
      significant to persons with brain injury, such as funding for services,
      coexisting diagnoses, and limited self-advocacy. Organizationally specific
      barriers included funding for services, limited training and education, and
      systems resources (e.g., personnel). Adding depth and insight, qualitative
      findings triangulated with these results, also highlighting the prevalence of the
      funding barrier and pointing to additional barriers relative to the individual,
      the family, and external stigma. CONCLUSIONS: The need for convenient, cost
      effective, and applicable training and education is paramount. Opportunities for
      interagency cross training and education, particularly around risk assessment,
      psychosocial adjustment symptoms, and the biomechanical causes of psychiatric
      symptoms may alleviate perceived disconnections, improve provider confidence, and
      mitigate crises. Developing interprofessional teams of providers to maximize
      access to services, either face-to-face or virtual, is integral. These
      perspectives highlight opportunities to improve access to services and to
      strengthen relationships across providers and agencies.

PMID- 24128270
TI  - Papillary fibroelastoma of the pulmonary valve--a systematic review.
AB  - The pulmonary valve is the least affected site for valvular papillary
      fibroelastoma. With increasing use of routine echocardiography and other
      modalities of imaging, pulmonary valve papillary fibroelastomas (PVPFE) are being
      recognized more frequently. PVPFE is more often an incidental diagnosis and
      symptomatic patients usually present with shortness of breath. Embolic phenomena
      and right ventricular outflow tract obstruction are the most serious
      complications of PVPFE. Since PVPFE is rare, the purpose of this systematic
      review is to address demographic characteristics, the clinical presentation,
      management, and outcome of this benign tumor of the pulmonary valve. 

PMID- 24128271
TI  - Optimizing the properties of the protein corona surrounding nanoparticles for
      tuning payload release.
AB  - We manipulate the passive release rates of DNA payloads on protein coronas formed
      around nanoparticles (NPs) by varying the corona composition. The coronas are
      prepared using a mixture of hard and soft corona proteins. We form coronas around
      gold nanorods (NRs), nanobones (NBs), and carbon nanotubes (CNTs) from human
      serum (HS) and find that tuning the amount of human serum albumin (HSA) in the NR
      coronas (NR-HS-DNA) changes the payload release profile. The effect of buffer
      strength, HS concentration, and concentration of the cetyltrimethylammonium
      bromide (CTAB) passivating the NP surfaces on passive release is explored. We
      find that corona properties play an important role in passive release, and
      concentrations of CTAB, HS, and phosphate buffer used in corona formation can
      tune payload release profiles. These advances in understanding protein corona
      properties bring us closer toward developing a set of basic design rules that
      enable their manipulation and optimization for particular biological
      applications. 

PMID- 24128272
TI  - Prospective study of mobilization kinetics up to 18 hours after late-afternoon
      dosing of plerixafor.
AB  - BACKGROUND: The current FDA-approved time interval between plerixafor dosing and
      apheresis initiation is approximately 11 hours, but this time interval is
      impractical for most care providers. Few studies have examined mobilization
      kinetics beyond 11 hours in multiple myeloma (MM) and non-Hodgkin's lymphoma
      (NHL) patients. Therefore, this study's intent was to analyze an interval of 17
      to 18 hours between plerixafor dosing and apheresis initiation. STUDY DESIGN AND
      METHODS: In 11 patients with MM or NHL, 240 MUg/kg plerixafor was administered at
      5 p.m. on Day 4 of granulocyte-colony-stimulating factor (G-CSF) mobilization.
      Peripheral blood (PB) CD34+ and CD34+CD38- concentrations were enumerated every 2
      hours until 7 a.m. and immediately before apheresis on Day 5, for a total
      interval time of 17 to 18 hours after plerixafor. Data were analyzed using mixed
      model analysis of repeated measures and paired t testing. RESULTS: Ten of the 11
      subjects achieved a CD34+ product count of more than 2 * 10(6) /kg with a single
      leukapheresis procedure. All 10 had a preplerixafor PB CD34+ concentration
      ([CD34+]) of at least 10/MUL. PB [CD34+] was not different between 10 and 18
      hours after plerixafor (p = 0.8). In contrast, PB CD34+CD38- concentrations
      significantly increased from 10 to 18 hours after plerixafor (p = 0.03).
      CONCLUSIONS: In MM and NHL patients with adequate preplerixafor [CD34+],
      leukapheresis initiated 14 to 18 hours after plerixafor and G-CSF mobilization
      may not impair adequate CD34+ collection and may increase more primitive
      CD34+CD38- collection. In this subset of patients, late-afternoon dosing of
      plerixafor at 5 p.m. with initiation of next-day apheresis as late as 11 a.m.
      appears feasible without loss of efficacy.

PMID- 24128273
TI  - Smart "lanthano" proteins for phospholipid sensing.
AB  - Metal-ion-mediated interactions between calcium-binding peripheral proteins and
      membrane phospholipids is a key feature of multiple cell signaling processes. The
      molecular basis for the interaction involves the displacement of inner-sphere
      water molecules on calcium ions by phosphate groups of the phospholipids. On the
      basis of this fundamental mechanism, we have devised a novel "turn-on" optical
      sensing strategy for anionic phospholipids by using a lanthanide reconstituted
      protein. The "lanthano" protein turns on selectively in the presence of a crucial
      signaling phospholipid, phosphatidylserine, by affording a 6 times enhancement in
      lanthanide luminescence. The "turn-on" sensing strategy was distinctly validated
      by direct evidence for the water-displacement mechanism via lifetime
      measurements. 

PMID- 24128274
TI  - Remarkable behavior of a bifunctional alkynylborane zirconocene complex toward
      donor ligands and acetylenes.
AB  - Treatment of a [(trimethylsilylethynyl)alkenyl]ZrCp2 complex with Piers' borane
      [HB(C6F5)2] resulted in the clean formation of the Zr/B complex [eta(2)-(C6F5)2B
      C=C-SiMe3]ZrCp2 (3). This compound shows some unique reaction patterns. With a
      variety of typical donor ligands (carbon monoxide, an isonitrile, a nitrile, THF
      d8,) it forms the respective adducts 5 (four examples characterized by X-ray
      diffraction). Toward terminal alkynes (RC=CH) compound 3 behaves as a Zr(II)
      metal Lewis base/boron Lewis acid frustrated Lewis pair (FLP) and undergoes
      typical regioselective 1,2-Zr/B addition reactions to yield the
      metallaheterocyclic products 7 (four examples characterized by X-ray
      diffraction). Compound 3 also undergoes characteristic 1,4-Zr/B FLP addition to a
      silyl-substituted conjugated enyne (to give 9) and also to 1,4
      bis(trimethylsilyl)butadiyne to yield a metallacyclic butatriene derivative 10
      (both 9 and 10 were characterized by X-ray diffraction). Eventually, compound 3
      reacted with mes2P-C=CH to give the metallacycloallenoid product 15, which was
      probably formed by means of 1,2-Zr/B FLP addition followed by alkynyl shift from
      boron to zirconium and reductive coupling. Treatment of 3 with tolane gave the
      closely related zirconacycloallenoid complex 16 by carbon carbon coupling. Both
      the products 15 and 16 were characterized by X-ray diffraction. 

PMID- 24128275
TI  - Structural destabilization of DNA duplexes containing single-base lesions
      investigated by nanopore measurements.
AB  - The influence of DNA duplex structural destabilization introduced by a single
      base-pair modification was investigated by nanopore measurements. A series of 11
      modified base pairs were introduced into the context of an otherwise
      complementary DNA duplex formed by a 17-mer and a 65-mer such that the
      overhanging ends comprised poly(dT)23 tails, generating a representative set of
      duplexes that display a range of unzipping mechanistic behaviors and kinetic
      stabilities. The guanine oxidation products 8-oxo-7,8-dihydroguanine (OG),
      guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp) were paired with either
      cytosine (C), adenine (A), or 2,6-diaminopurine (D) to form modified base pairs.
      The mechanism and kinetic rate constants of duplex dissociation were determined
      by threading either the 3' or 5' overhangs into an alpha-hemolysin (alpha-HL)
      channel under an electrical field and measuring the distributions of unzipping
      times at constant force. In order of decreasing thermodynamic stability (as
      measured by duplex melting points), the rate of duplex dissociation increases,
      and the mechanism evolves from a first-order reaction to two sequential first
      order reactions. These measurements allow us to rank the kinetic stability of
      lesion-containing duplexes relative to the canonical G:C base pair in which the
      OG:C, Gh:C, and Sp:C base pairs are, respectively, 3-200 times less stable. The
      rate constants also depend on whether unzipping was initiated from the 3' versus
      5' side of the duplex. The kinetic stability of these duplexes was interpreted in
      terms of the structural destabilization introduced by the single base-pair
      modification. Specifically, a large distortion of the duplex backbone introduced
      by the presence of the highly oxidized guanine products Sp and Gh leads to a
      rapid two-step unzipping. The number of hydrogen bonds in the modified base pair
      plays a lesser role in determining the kinetics of duplex dissociation. 

PMID- 24128277
TI  - Lersivirine - a new drug for HIV infection therapy.
AB  - INTRODUCTION: Lersivirine (UK-453,061) is a novel second-generation non
      nucleoside reverse transcriptase inhibitor (NNRTI). It binds reverse
      transcriptase in a distinct way leading to a unique resistance profile. The
      development of lersivirine was recently stopped in Phase IIb clinical
      development. AREAS COVERED: This article describes the background of lersivirine,
      its pharmacodynamic and pharmacokinetic profile and its clinical efficacy in HIV
      infected patients. Moreover, the authors review its resistance profile in
      addition to its possible interactions with coadministered drugs and safety and
      tolerability. The authors' evaluation is based on the articles retrieved from a
      Medline in addition to abstracts from major HIV conferences and workshops
      addressing lersivirine. EXPERT OPINION: The authors believe that lersivirine has
      therapeutic potential for HIV-infected individuals with viral strains resistant
      against first-line NNRTIs. However, no large, well-powered studies have been
      conducted so far, which assess noninferiority against established antiretroviral
      agents. In February 2013, the developing company behind lersivirine halted
      further development as it was decided that it would not provide an improvement
      over existing therapies; perhaps this is an opportunity missed.

PMID- 24128278
TI  - Heart rate and heart rate variability modification in chronic insomnia patients.
AB  - Chronic insomnia is highly prevalent in the general population, provoking
      personal distress and increased risk for psychiatric and medical disorders.
      Autonomic hyper-arousal could be a pathogenic mechanism of chronic primary
      insomnia. The aim of this study was to investigate autonomic activity in patients
      with chronic primary insomnia by means of heart rate variability (HRV) analysis.
      Eighty-five consecutive patients affected by chronic primary insomnia were
      enrolled (38 men and 47 women; mean age: 53.2 +/- 13.6). Patients were compared
      with a control group composed of 55 healthy participants matched for age and
      gender (23 men and 32 women; mean age: 54.2 +/- 13.9). Patients underwent an
      insomnia study protocol that included subjective sleep evaluation, psychometric
      measures, and home-based polysomnography with evaluation of HRV in wake before
      sleep, in all sleep stages, and in wake after final awakening. Patients showed
      modifications of heart rate and HRV parameters, consistent with increased
      sympathetic activity, while awake before sleep and during Stage-2 non-REM sleep.
      No significant differences between insomniacs and controls could be detected
      during slow-wave sleep, REM sleep, and post-sleep wake. These results are
      consistent with the hypothesis that autonomic hyper-arousal is a major pathogenic
      mechanism in primary insomnia, and confirm that this condition is associated with
      an increased cardiovascular risk. 

PMID- 24128280
TI  - Using genomic tools to maintain diversity and fitness in conservation programmes.
AB  - Conservation programmes aim at maximizing the survival probability of
      populations, by minimizing the loss of genetic diversity, which allows
      populations to adapt to changes, and controlling inbreeding increases. The best
      known strategy to achieve these goals is optimizing the contributions of the
      parents to minimize global coancestry in their offspring. Results on neutral
      scenarios showed that management based on molecular coancestry could maintain
      more diversity than management based on genealogical coancestry when a large
      number of markers were available. However, if the population has deleterious
      mutations, managing using optimal contributions can lead to a decrease in
      fitness, especially using molecular coancestry, because both beneficial and
      harmful alleles are maintained, compromising the long-term viability of the
      population. We introduce here two strategies to avoid this problem: The first one
      uses molecular coancestry calculated removing markers with low minor allele
      frequencies, as they could be linked to selected loci. The second one uses a
      coancestry based on segments of identity by descent, which measures the
      proportion of genome segments shared by two individuals because of a common
      ancestor. We compare these strategies under two contrasting mutational models of
      fitness effects, one assuming many mutations of small effect and another with few
      mutations of large effect. Using markers at intermediate frequencies maintains a
      larger fitness than using all markers, but leads to maintaining less diversity.
      Using the segment-based coancestry provides a compromise solution between
      maintaining diversity and fitness, especially when the population has some
      inbreeding load. 

PMID- 24128281
TI  - Tumoral calcinosis in systemic sclerosis associated with multicentric Castleman's
      disease.

PMID- 24128276
TI  - Intravascular immunity as a key to systemic vasculitis: a work in progress,
      gaining momentum.
AB  - Vascular inflammation contributes to the defence against invading microbes and to
      the repair of injured tissues. In most cases it resolves before becoming
      apparent. Vasculitis comprises heterogeneous clinical entities that are
      characterized by the persistence of vascular inflammation after it has served its
      homeostatic function. Most underlying mechanisms have so far remained elusive.
      Intravascular immunity refers to the surveillance of the vasculature by
      leucocytes that sense microbial or sterile threats to vessel integrity and
      initiate protective responses that entail most events that determine the clinical
      manifestations of vasculitis, such as end-organ ischaemia, neutrophil
      extracellular traps generation and thrombosis, leucocyte extravasation and
      degranulation. Understanding how the resolution of vascular inflammation goes
      awry in patients with systemic vasculitis will facilitate the identification of
      novel pharmacological targets and bring us a step closer in each patient to the
      selection of more effective and less toxic treatments. 

PMID- 24128282
TI  - Demographic responses of a site-faithful and territorial predator to its
      fluctuating prey: long-tailed skuas and arctic lemmings.
AB  - Environmental variability, through interannual variation in food availability or
      climatic variables, is usually detrimental to population growth. It can even
      select for constancy in key life-history traits, though some exceptions are
      known. Changes in the level of environmental variability are therefore important
      to predict population growth or life-history evolution. Recently, several cyclic
      vole and lemming populations have shown large dynamical changes that might affect
      the demography or life-histories of rodent predators. Skuas constitute an
      important case study among rodent predators, because of their strongly saturating
      breeding productivity (they lay only two eggs) and high degree of site fidelity,
      in which they differ from nomadic predators raising large broods in good rodent
      years. This suggests that they cannot capitalize on lemming peaks to the same
      extent as nomadic predators and might be more vulnerable to collapses of rodent
      cycles. We develop a model for the population dynamics of long-tailed skuas
      feeding on lemmings to assess the demographic consequences of such variable and
      non-stationary prey dynamics, based on data collected in NE Greenland. The model
      shows that populations of long-tailed skua sustain well changes in lemming
      dynamics, including temporary collapses (e.g. 10 years). A high floater-to
      breeder ratio emerges from rigid territorial behaviour and a long-life
      expectancy, which buffers the impact of adult abundance's decrease on the
      population reproductive output. The size of the floater compartment is affected
      by changes in both mean and coefficient of variation of lemming densities (but
      not cycle amplitude and periodicity per se). In Greenland, the average lemming
      density is below the threshold density required for successful breeding
      (including during normally cyclic periods). Due to Jensen's inequality, skuas
      therefore benefit from lemming variability; a positive effect of environmental
      variation. Long-tailed skua populations are strongly adapted to fluctuating
      lemming populations, an instance of demographic lability in the reproduction
      rate. They are also little affected by poor lemming periods, if there are enough
      floaters, or juveniles disperse to neighbouring populations. The status of
      Greenland skua populations therefore strongly depends upon floater numbers and
      juvenile movements, which are not known. This reveals a need to intensify colour
      ringing efforts on the long-tailed skua at a circumpolar scale.

PMID- 24128283
TI  - Audiovestibular functions in noninsulin-dependent diabetes mellitus.
AB  - CONCLUSION: This study supports the proposition that vestibular dysfunction and
      sensorineural hearing loss (SNHL) may be considered among the complications due
      to noninsulin-dependent diabetes mellitus (NIDDM). OBJECTIVE: The aim of this
      study was to evaluate the audiovestibular functions in patients with NIDDM and to
      determine if there is any correlation between audiovestibular dysfunction and the
      duration of the disease. METHODS: A total of 104 patients diagnosed with NIDDM
      and 104 nondiabetic control subjects made up the study group. Diabetic patients
      were also divided into subgroups of <=7 years and >7 years according to the
      duration of the disease. Pure-tone audiometry (PTA), speech recognition scores
      (SRS), impedance audiometry, and vestibular function tests (VFT) were performed
      for all of the patients. RESULTS: Hearing thresholds in all frequencies (except
      at 500 Hz for bone conduction) and SRS values were statistically significant in
      patients with NIDDM and control subjects, but there was no statistically
      significant difference according to the duration of the disease. Statistically
      significant alterations were present in VFT in patients with NIDDM compared with
      the control subjects. In the diabetic group, only failure in the saccade test was
      statistically significant according to the duration of the disease.

PMID- 24128284
TI  - Surgical results of the intraoral approach for plunging ranula.
AB  - CONCLUSIONS: The intraoral approach for removal of the plunging ranula is a safe
      and effective surgical approach as a primary treatment modality for plunging
      ranula. OBJECTIVES: Although sclerotherapy is applied for plunging ranula, it can
      be primarily treated with surgery such as marsupialization, simple excision, and
      transcervical excision. This study was performed to assess the results of the
      intraoral approach for the treatment of plunging ranula. METHODS: This
      prospective clinical study comprised a total of 23 patients with plunging ranula
      treated by the intraoral approach. RESULTS: All patients had complete removal of
      the sublingual gland with evacuation of cystic fluid. The cystic wall of the
      ranula could be dissected completely in only four patients, and in eight patients
      it was only possible to drain the cystic fluid. However, in 11 patients we could
      not dissect the cystic wall completely. Rupture of ranula developed in all
      patients during the intraoral dissection. Recurrence was not detected in any of
      the patients during the median follow-up period of 14 months after the intraoral
      excision. There were no complications or external scarring.

PMID- 24128285
TI  - Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit
      tumor growth and metastasis.
AB  - BACKGROUND: Endostatin (ES) inhibits endothelial cell proliferation, migration,
      invasion, and tube formation. It also shows antiangiogenesis and antitumor
      activities in several animal models. Endostatin specifically targets tumor
      vasculature to block tumor growth. Lidamycin (LDM), which consists of an active
      enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a
      member of chromoprotein family of antitumor antibiotics with extremely potent
      cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin
      (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the
      combined capability targeting tumor vasculature and tumor cell by respective ES
      and LDM moiety. METHODS: In this study, we designed and obtained two new
      endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP
      ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the
      wound healing assay and tube formation assay and the cytotoxicity of their
      enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was
      used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human
      lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was
      evaluated with human lung carcinoma PG-BE1 xenograft and the experimental
      metastasis model of 4T1-luc breast cancer. RESULTS: ES-LDP and LDP-ES disrupted
      the formation of endothelial tube structures and inhibited endothelial cell
      migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth
      and metastasis. ES-LDP and ES show higher binding capability than LDP to lung
      carcinoma; in addition, ES-LDP and ES share similar binding capability.
      Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated
      significant efficacy against lung carcinoma xenograft in athymic mice.
      CONCLUSIONS: The ES-based fusion protein therapy provides some fundamental
      information for further drug development. Targeting both tumor vasculature and
      tumor cells by endostatin-based fusion proteins and their enediyne-energized
      analogs probably provides a promising modality in cancer therapy.

PMID- 24128286
TI  - Ecological momentary assessment of the effects of craving and affect on risk for
      relapse during substance abuse treatment.
AB  - The primary goals of this study were to use ecological momentary assessment (EMA)
      to examine the extent to which proximal factors (cravings and affect) were
      temporally associated with relapse, and to assess the role of distal factors
      (e.g., coping styles) in moderating these associations. We also examined whether
      using EMA procedures impacted relapse rates. A sample of 100 male (n = 66) and
      female (n = 34) patients entering outpatient treatment for substance abuse
      completed a baseline assessment of substance dependence, stress, social support,
      coping styles, family history of substance abuse, and self-efficacy. Half of the
      participants were randomly assigned to receive training in using a handheld
      computer to respond to 3 random prompts each day for 4 months regarding cravings,
      affect, and substance use. All participants completed 2- and 4-month follow-up
      assessments of substance use. Results showed that using EMA procedures did not
      influence relapse rates. Hierarchical linear modeling showed that individuals who
      reported an increase in cravings on a given prompt were 14 times more likely to
      report relapse on the subsequent prompt than individuals who did not experience
      an increase in cravings. In addition, women, older individuals, and individuals
      who use distraction and disengagement as coping styles were at increased risk for
      relapse when experiencing an increase in cravings. Individuals who use acceptance
      as a coping style were at decreased risk for relapse when experiencing an
      increase in cravings. The study highlights the importance of tailoring treatments
      to address the needs of particular individuals and risk factors.

PMID- 24128287
TI  - Concordant and discordant alcohol, tobacco, and marijuana use as predictors of
      marital dissolution.
AB  - This study examined concordant and discrepant alcohol, tobacco, and marijuana use
      among couples to determine whether they predicted marital separation or divorce
      over 9 years. The study recruited 634 couples as they applied for their marriage
      licenses; we assessed them at that time and reassessed them with mailed
      questionnaires at their first, second, fourth, seventh, and ninth wedding
      anniversaries. Approximately 60% of the men and women were European American, and
      approximately 33% were African American. The frequency of drinking to
      intoxication and binge drinking (more than 5 drinks in an occasion) was assessed,
      as was the use of cigarettes and marijuana. At each assessment, each member of
      the couple was asked about the occurrence of marital separations and divorce.
      Bivariate analyses indicated that tobacco and marijuana use, whether discrepant
      or concordant, were associated with marital disruptions. However, discrepant
      heavy drinking was associated with disruptions, but concordant heavy drinking was
      not. Concordant and discordant marijuana use were not associated with divorce
      when analyses controlled for alcohol and tobacco use. Concordant and discordant
      tobacco use was not associated with divorce when analyses controlled for
      sociodemographic and personality factors. However, discrepant alcohol use was
      related to divorce after controlling for the other substances in 1 analysis and
      after controlling for the sociodemographic factors in a separate analysis.
      Tobacco and marijuana use were related to divorce through their associations with
      other variables. However, results suggest that discrepant alcohol use may lead to
      marital disruptions and should be addressed with couples seeking marital
      treatment.

PMID- 24128288
TI  - Urgency traits and problematic substance use in adolescence: Direct effects and
      moderation of perceived peer use.
AB  - Negative and positive urgency are facets of trait impulsivity that have been
      identified as possible risk factors for problematic substance use. Relationships
      between these traits and substance use measures have not yet been widely
      investigated in adolescents. In the current study, a sample of 270 adolescent
      students completed self-report measures of impulsivity-related traits, their
      alcohol and cannabis use, problematic use, and perceived peer use. Zero-inflated
      negative binomial regression models indicated that both urgency traits accounted
      for significant variance in problematic alcohol and cannabis use scores, even
      after accounting for nonurgency impulsivity traits and typical substance
      consumption. Furthermore, both urgency traits moderated the positive association
      between perceived peer alcohol use and individual problematic use. Results
      indicate that the urgency traits show a direct association with problematic
      substance use in adolescence, and that high urgency adolescents who believe their
      peers drink high levels of alcohol may be at increased risk of problematic
      alcohol use.

PMID- 24128289
TI  - Brain reward region responsivity of adolescents with and without parental
      substance use disorders.
AB  - The present study tested the competing hypotheses that adolescents at risk for
      future substance abuse and dependence by virtue of parental substance use
      disorders show either weaker or stronger responsivity of brain regions implicated
      in reward relative to youth without parental history of substance use disorders.
      Adolescents (n = 52) matched on demographics with and without parental substance
      use disorders, as determined by diagnostic interviews, who denied substance use
      in the past year were compared on functional MRI (fMRI) paradigms assessing
      neural response to receipt and anticipated receipt of monetary and food reward.
      Parental-history-positive versus -negative adolescents showed greater activation
      in the left dorsolateral prefrontal cortex and bilateral putamen, and less
      activation in the fusiform gyrus and inferior temporal gyrus in response to
      anticipating winning money, as well as greater activation in the left midbrain
      and right paracentral lobule, and less activation in the right middle frontal
      gyrus in response to milkshake receipt. Results indicate that adolescents at risk
      for future onset of substance use disorders show elevated responsivity of brain
      regions implicated in reward, extending results from 2 smaller prior studies that
      found that individuals with versus without parental alcohol use disorders showed
      greater reward region response to anticipated monetary reward and pictures of
      alcohol. Collectively, results provide support for the reward surfeit model of
      substance use disorders, rather than the reward deficit model.

PMID- 24128290
TI  - Patterns of change in affect and adrenocortical activity over an extended period
      of smoking abstinence.
AB  - This study examined patterns of change in postcessation withdrawal symptoms and
      basal adrenocortical activity of smokers who were abstinent over a 4-week period
      (n = 18) and those who relapsed within the first week (n = 35). Participants
      interested in smoking cessation attended a prequit assessment in which they
      completed multiple forms associated with smoking withdrawal and provided a saliva
      sample for cortisol and cotinine measures. Then, the participants were asked to
      set a quit day and were required to abstain from smoking for at least 24 hours.
      After that, the participants attended four weekly follow-up support sessions
      during which self-report measures on withdrawal symptoms and tobacco use and
      saliva samples were collected. Smoking status was confirmed biochemically. We
      found that, overall, the abstinent smokers reported lower withdrawal symptoms,
      craving, and negative affect than relapsed smokers. Further exploratory analysis
      indicated that prequit withdrawal severity was lower in those who were abstinent
      than in those who eventually relapsed. Craving and physical symptoms in
      abstainers decreased as distress in relapsers increased during the follow-up
      period. Smoking urges diminished in both groups. Reported numbers of cigarettes
      per day after the failure of a quit attempt were lower than their precessation
      baseline. Cortisol did not differ by group or by time. Despite using a cross
      sectional method, these results may suggest individual differences in negative
      symptoms while smoking regularly, and abstinence may be associated with reduction
      of craving and physical symptoms. The findings also suggested that relapsers may
      not immediately bring back their regular smoking habit after having relapsed.

PMID- 24128291
TI  - Longitudinal change mechanisms for substance use and illegal activity for
      adolescents in treatment.
AB  - The current study investigated: (a) the relationships of exposure to the
      Adolescent Community Reinforcement Approach (A-CRA) with reductions in substance
      use, illegal activity, and juvenile justice system involvement in adolescents
      diagnosed with a substance use disorder, and (b) the pathways by which reductions
      in the target behaviors were achieved. This study is a secondary data analysis of
      longitudinal data from a large-scale implementation effort for A-CRA. The sample
      consisted of 1,467 adolescents who presented to substance use treatment and
      reported past-year engagement in illegal activity. Participants had an average
      age of 15.8 years (SD = 1.3) and were 25% female, 14% African American, 29%
      Hispanic, 35% Caucasian, 16% mixed ethnicity, and 6% other ethnicity. Path
      analyses provided support that participation in A-CRA had a significant, direct
      association with reduced substance use; a significant, indirect association with
      reduced illegal activity through reductions in substance use; and a significant
      indirect association with reduced juvenile justice system involvement through
      reductions in both substance use and illegal activity. In addition, post hoc
      analyses using a bootstrapping strategy provided evidence that reductions in
      substance use partially mediated the relationship between A-CRA and illegal
      activity.

PMID- 24128292
TI  - Staff commitment to providing tobacco dependence in drug treatment: Reliability,
      validity, and results of a national survey.
AB  - Although most people in treatment for illicit drug use smoke cigarettes, few
      facilities offer any form of treatment for tobacco dependence. One reason for
      this may be that drug treatment staff have varying levels of commitment to treat
      tobacco. We developed and validated a 14-item Tobacco Treatment Commitment Scale
      (TTCS), using 405 participants in leadership positions in drug treatment
      facilities. We first conducted a confirmatory factor analysis to evaluate 4 a
      priori domains suggested by our original set of 38 items-this did not produce a
      good fit (comparative fit index [CFI] = 0.782, root mean square error of
      approximation [RMSEA] = 0.067). We then conducted a series of exploratory factor
      analyses to produce a more precise and reliable scale. The final confirmatory
      factor analysis indicated a 3-factor solution, produced a good fit (CFI = 0.950,
      RMSEA = 0.058), and had substantial unified reliability of 0.975. The final TTCS
      contained 14 items in 3 domains: "Tobacco is less harmful than other drugs,"
      "It's not our job to treat tobacco," and "Tobacco treatment will harm clients."
      These constructs account for most of the variance in the survey items and emerged
      as major sentiments driving staff commitment to providing tobacco services. The
      TTCS can be used to understand the role of staff attitudes in the adoption of
      tobacco services in this important treatment setting.

PMID- 24128294
TI  - Old-aged case of indolent grade III lymphomatoid granulomatosis successfully
      treated only with oral prednisolone.

PMID- 24128293
TI  - What are other parents saying? Perceived parental communication norms and the
      relationship between alcohol-specific parental communication and college student
      drinking.
AB  - This study examined parents' normative perceptions of other college parents'
      alcohol-specific communication, and how parents' perceived communication norms
      and alcohol-specific communication relate to student drinking outcomes. A sample
      of 457 student-parent dyads were recruited from a midsize university. Students
      completed Web-based assessments of alcohol-related attitudes and behaviors.
      Parents completed alcohol-specific measures of communication norms and parent
      child communication, including communication content (i.e., targeted
      communication) and frequency of communication. Results indicated that parents
      overestimated how much other parents talked to their college students about the
      frequency and quantity of alcohol use, but underestimated how often parents
      initiated conversations about alcohol. In a path model, perceived communication
      norms positively predicted both targeted communication and frequency of
      communication. Perceived communication norms and targeted communication
      negatively predicted students' attitude toward alcohol use. In contrast, more
      frequent communication predicted students holding more approving attitudes toward
      alcohol. The relationship between parents' perceived communication norms and
      students' drinking behaviors was mediated by the parental communication variables
      and student attitudes. Tests of indirect effects were undertaken to examine
      meditational processes. The findings underscore relations involving parental
      perceived communication norms and parents' own alcohol communication and their
      children's drinking outcomes. The complex relationships of different types of
      parental communication and student outcomes warrant further research.

PMID- 24128295
TI  - The role of social environment on parental care: offspring benefit more from the
      presence of female than male helpers.
AB  - Investment in offspring depends on the costs and benefits to the carer, which can
      vary with sex and social status. Investment also depends on the effort of others
      by allowing for compensation (load-lightening), with biparental care studies
      showing that this depends on the state and type of the other carer. By contrast,
      studies on cooperative breeders have solely focussed on the effects of group size
      rather than its composition (i.e. social environment). Here we propose and
      provide the first test of the 'Social Environment' hypothesis, that is, how the
      characteristics (here the sex) of other helpers present in the group affect
      parental care and how this in turn affects offspring fitness in cooperatively
      breeding red-winged fairy-wrens (Malurus elegans). Breeders provisioned nestlings
      at a higher rate than helpers, but there was no sex difference in provisioning
      rate. Compensation to increasing group size varied little with sex and status,
      but strongly depended on social environment. All group members reduced their
      provisioning rates in response to an increasing number of male (load-lightening),
      but not female helpers (additive care). As a result, nestlings received more food
      and grew faster in the presence of female helpers. The increased nestling growth
      did convey a fitness advantage due to a higher post-fledging survival to
      adulthood. Our study provides the first evidence that parental care can depend on
      social environment. This could be an important overlooked aspect to explain
      variation in parental care in cooperative breeders in general and in particular
      the enormous variation between the sexes, which we reveal in a literature
      overview. 

PMID- 24128296
TI  - OsACA6, a P-type IIB Ca2+ ATPase promotes salinity and drought stress tolerance
      in tobacco by ROS scavenging and enhancing the expression of stress-responsive
      genes.
AB  - Calcium (Ca2+) regulates several signalling pathways involved in growth,
      development and stress tolerance. Cellular Ca2+ homeostasis is achieved by the
      combined action of channels, pumps and antiporters, but direct evidence for a
      role of Ca2+ATPase pumps in stress tolerance is lacking. Here we report the
      characterization of a Ca2+ ATPase gene (OsACA6) from Oryza sativa, and elucidate
      its functions in stress tolerance. OsACA6 transcript levels are enhanced in
      response to salt, drought, abscisic acid and heat. In vivo localization
      identified plasma membranes as an integration site for the OsACA6-GFP fusion
      protein. Using transgenic tobacco lines, we demonstrate that over-expression of
      OsACA6 is triggered during salinity and drought stresses. The enhanced tolerance
      to these stresses was confirmed by changes in several physiological indices,
      including water loss rate, photosynthetic efficiency, cell membrane stability,
      germination, survival rate, malondialdehyde content, electrolyte leakage and
      increased proline accumulation. Furthermore, over-expressing lines also showed
      higher leaf chlorophyll and reduced accumulation of H2O2 and Na+ ions compared to
      the wild-type. Reduced accumulation of reactive oxygen species (ROS) was observed
      in transgenic lines. The increased proline accumulation and ROS scavenging enzyme
      activities in transgenic plants over-expressing OsACA6 efficiently modulate the
      ROS machinery and proline biosynthesis through an integrative mechanism.
      Transcriptional profiling of these plants revealed altered expression of genes
      encoding many transcription factors, stress- and disease-related proteins, as
      well as signalling components. These results suggest that Ca2+ ATPases have
      diverse roles as regulators of many stress signalling pathways, leading to plant
      growth, development and stress tolerance.

PMID- 24128298
TI  - Efficacy of AST-120 in dogs with chronic idiopathic enteropathies.
AB  - BACKGROUND: Chronic idiopathic enteropathies (CIE) in dogs are complex diseases
      of unknown origin. AST-120 is a spherical carbon adsorbent preparation with a
      high adsorption ability for low molecular substances. OBJECTIVES: Evaluation of
      the clinical efficacy of AST-120 in dogs with CIE. ANIMALS: Ten client-owned dogs
      with mild (n = 7) to moderate (n = 3) CIE. METHODS: Explorative, prospective,
      randomized, placebo-controlled, double-blinded pilot study. Dogs with chronic
      diarrhea and no or insufficient response to an elimination diet were included.
      The dogs received either AST-120 (n = 5) or placebo (n = 5) for a duration of 21
      days. The canine inflammatory bowel disease activity index (CIBDAI) was used to
      assess disease severity at baseline and clinical outcome after 3 weeks of
      treatment. Furthermore, changes in body weight and the parameters stool
      consistency and frequency were compared within and between groups. RESULTS: The
      mean CIBDAI score decreased from 5.6 (SD 1.5) to 2.0 (SD 1.2) in the AST-120
      group (P = .125) and from 4.8 (SD .8) to 3.6 (SD 2.3) in the placebo group (P =
      .688). Compared with baseline, posttreatment CIBDAI scores decreased more than
      60% in 4/5 dogs treated with AST-120 and in 1/5 dogs treated with placebo (P =
      .206). Changes in CIBDAI scores, body weights, stool consistency, and frequency
      within and between groups did not achieve statistical significance after 3 weeks
      of treatment. No adverse effects of AST-120 were noted. CONCLUSIONS AND CLINICAL
      IMPORTANCE: This study investigated potential efficacy of AST-120 as an
      alternative therapy in dogs with mild-to-moderate CIE.

PMID- 24128300
TI  - Understanding mental and physical fatigue complaints in those with depression and
      insomnia.
AB  - Fatigue is a concern for both people with insomnia and with depression, yet it
      remains poorly understood. Participants (N = 62) included those meeting
      Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision)
      criteria for insomnia and major depressive disorder (MDD). Multiple regression
      examined sleep, mood, activity, and cognitive factors as predictors of mental and
      physical fatigue. Only the cognitive factors (i.e., unhelpful beliefs about sleep
      and symptom-focused rumination) were predictive of both physical and mental
      fatigue. Beliefs about not being able to function and needing to avoid activities
      after a poor night of sleep were related to both types of fatigue. Targeting
      these beliefs via cognitive therapy and encouraging patients to test maladaptive
      beliefs about sleep may enhance fatigue response in those with MDD and insomnia. 

PMID- 24128299
TI  - Reflex fluorescence in situ hybridization assay for suspicious urinary cytology
      in patients with bladder cancer with negative surveillance cystoscopy.
AB  - OBJECTIVE: To assess the ability of reflex UroVysion fluorescence in situ
      hybridization (FISH) testing to predict recurrence and progression in patients
      with non-muscle-invasive bladder cancer (NMIBC) with suspicious cytology but
      negative cystoscopy. PATIENTS AND METHODS: Patients under NMIBC surveillance were
      followed with office cystoscopy and urinary cytology every 3-6 months. Between
      March 2007 and February 2012, 500 consecutive patients with suspicious cytology
      underwent reflex FISH analysis. Clinical and pathological data were reviewed
      retrospectively. Predictors for recurrence, progression and findings on
      subsequent cystoscopy (within 2-6 months after FISH) were evaluated using
      univariate and multivariate Cox regression. RESULTS: In all, 243 patients with
      suspicious cytology also had negative surveillance cystoscopy. Positive FISH was
      a significant predictor of recurrence (hazard ratio [HR] = 2.35, 95% confidence
      interval [CI]: 1.42-3.90, P = 0.001) in multivariate analysis and for progression
      (HR = 3.01, 95% CI: 1.10-8.21, P = 0.03) in univariate analysis, compared with
      negative FISH. However, positive FISH was not significantly associated with
      evidence of tumour on subsequent surveillance cystoscopy compared with negative
      FISH (odds ratio = 0.8, 95% CI: 0.26-2.74, P = 1). CONCLUSIONS: Positive FISH
      predicts recurrence and progression in patients under NMIBC surveillance with
      suspicious cytology but negative cystoscopy. However, there was no association
      between the FISH result and tumour recurrence in the immediate follow-up period.
      Reflex FISH testing for suspicious cytology might have limited ability to modify
      surveillance strategies in NMIBC.

PMID- 24128301
TI  - Diabetes mellitus in Jamaica: sex differences in burden, risk factors, awareness,
      treatment and control in a developing country.
AB  - OBJECTIVE: The objective of this study was to provide valid estimates of the
      burden of and risk factors for diabetes mellitus by sex in Jamaica, a
      predominantly Black, middle-income and developing country. METHODS: The Jamaica
      Health and Lifestyle Survey 2008 examined a nationally representative sample of
      2848 Jamaicans aged 15-74. Parameter estimates and 95% confidence intervals [CI]
      were weighted for non-response as well as age and sex of the source population.
      Sex differences in risk factors and diabetes prevalence, awareness, treatment and
      control were estimated in multivariable models. Population-attributable fractions
      (PAFs) of obesity on diabetes mellitus were estimated in both sexes. RESULTS: The
      prevalence of diabetes mellitus was 7.9% (95% CI: 6.7-9.1%), significantly higher
      in women than men 9.3% vs. 6.4% (P = 0.02) and increasing with age. Seventy-six
      percentage of persons with diabetes mellitus were aware of their status; urban
      women and rural men were less likely to be aware. Diabetes control (43% overall)
      was less common in higher-income men, but more common in higher-income women.
      Persons without health insurance were less likely to control their diabetes. The
      prevalence of diabetes risk factors was higher in women than men. Increased waist
      circumference (>=94 cm [men]/>=80 cm [women]), overweight/obesity (body mass
      index >= 25 kg/m(2)) and low physical activity/inactivity were associated with
      PAFs for diabetes mellitus of 27%, 37% and 15%, respectively, in men and 77%, 54%
      and 24%, respectively, in women. CONCLUSIONS: Prevalence of diabetes mellitus and
      its risk factors is high in Jamaica, especially among women, and national
      programmes to stem the diabetes mellitus epidemic should take these sex
      differences into consideration.

PMID- 24128302
TI  - Laparoscopic elective sigmoidectomy for diverticular disease: a plea for
      standardization of the procedure.

PMID- 24128303
TI  - Dissecting the contribution of thrombin exosite I in the recognition of thrombin
      binding aptamer.
AB  - Thrombin plays a pivotal role in the coagulation cascade; therefore, it
      represents a primary target in the treatment of several blood diseases. The 15
      mer DNA oligonucleotide 5'-GGTTGGTGTGGTTGG-3', known as thrombin binding aptamer
      (TBA), is a highly potent inhibitor of the enzyme. TBA folds as an antiparallel
      chair-like G-quadruplex structure, with two G-tetrads surrounded by two TT loops
      on one side and a TGT loop on the opposite side. Previous crystallographic
      studies have shown that TBA binds thrombin exosite I by its TT loops, T3T4 and
      T12T13. In order to get a better understanding of the thrombin-TBA interaction,
      we have undertaken a crystallographic characterization of the complexes between
      thrombin and two TBA mutants, TBADeltaT3 and TBADeltaT12, which lack the
      nucleobase of T3 and T12, respectively. The structural details of the two
      complexes show that exosite I is actually split into two regions, which
      contribute differently to TBA recognition. These results provide the basis for a
      more rational design of new aptamers with improved therapeutic action. 

PMID- 24128304
TI  - Axially chiral dicarboxylic acid catalyzed activation of quinone imine ketals:
      enantioselective arylation of enecarbamates.
AB  - The synthetic utility of quinone imine ketals in the context of asymmetric
      catalysis was disclosed for the first time. By expanding the utility of chiral
      Bronsted acid catalysis to the electrophilic activation of quinone imine ketals,
      we succeeded in the development of highly enantioselective arylation of
      encarbamates to give alpha-amino-beta-aryl ethers wherein quinone imine ketals
      act as functionalized aromatic ring surrogate. Further transformations of the
      products were also examined to establish procedures to provide chiral beta-aryl
      amines and alpha-aryl esters. 

PMID- 24128305
TI  - Drivers of population genetic differentiation in the wild: isolation by dispersal
      limitation, isolation by adaptation and isolation by colonization.
AB  - Empirical population genetic studies have been dominated by a neutralist view,
      according to which gene flow and drift are the main forces driving population
      genetic structure in nature. The neutralist view in essence describes a process
      of isolation by dispersal limitation (IBDL) that generally leads to a pattern of
      isolation by distance (IBD). Recently, however, conceptual frameworks have been
      put forward that view local genetic adaptation as an important driver of
      population genetic structure. Isolation by adaptation (IBA) and monopolization
      (M) posit that gene flow among natural populations is reduced as a consequence of
      local genetic adaptation. IBA stresses that effective gene flow is reduced among
      habitats that show dissimilar ecological characteristics, leading to a pattern of
      isolation by environment. In monopolization, local genetic adaptation of initial
      colonizing genotypes results in a reduction in gene flow that fosters the
      persistence of founder effects. Here, we relate these different processes driving
      landscape genetic structure to patterns of IBD and isolation by environment
      (IBE). We propose a method to detect whether IBDL, IBA and M shape genetic
      differentiation in natural landscapes by studying patterns of variation at
      neutral and non-neutral markers as well as at ecologically relevant traits.
      Finally, we reinterpret a representative number of studies from the recent
      literature by associating patterns to processes and identify patterns associated
      with local genetic adaptation to be as common as IBDL in structuring regional
      genetic variation of populations in the wild. Our results point to the importance
      of quantifying environmental gradients and incorporating ecology in the analysis
      of population genetics. 

PMID- 24128306
TI  - Human sorCS1 binds sortilin and hampers its cellular functions.
AB  - Sortilin and sorCS1 [sortilin-related Vps10p (vacuolar protein sorting/targeting
      protein 10) domain-containing receptor 1], both members of the Vps10p-D (Vps10p
      domain) receptor family, are synthesized as precursor proteins and are converted
      into their mature form by enzymatic cleavage of a short N-terminal propeptide.
      SorCS1 does not bind its propeptide, but sortilin is able to bind not just its
      own propeptide, but also that of sorCS1. In the present study we show that the
      propeptide region of sorCS1 contains two separate sites for binding to sortilin
      and that only one of these sites is removed from human (as opposed to mouse)
      sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding
      N-terminus, which allows formation of a complex between the two receptors in
      solution and on cell membranes. Furthermore, we find that the interaction with
      sorCS1 has a pronounced effect on sortilin's ability to mediate the cellular
      uptake of alternative ligands, and to hamper its facilitation of CNTF (ciliary
      neutrophic factor) signalling and the induction of phosphorylated STAT3 (signal
      transducer and activator of transcription 3). Thus the present study reveals a
      novel regulatory mechanism and suggest an entirely new role for sorCS1 as a
      modulator of sortilin function. 

PMID- 24128308
TI  - Re Letter to the editor re: Compalati E, Canonica GW. Efficacy and safety of
      rupatadine for allergic rhinoconjunctivitis: a systematic review of randomized,
      double-blind, placebo-controlled studies with meta-analysis. Curr Med Res Opin
      2013 Jul 5.

PMID- 24128309
TI  - Varying substituents and solvents to maximize the luminescence from
      [Ru(trpy)(bpy)CN]+ derivatives.
AB  - Ruthenium(II) in combination with monodentate, bidentate, and tridentate ligands
      has proven to be a useful design for a variety of applications, but the majority
      of systems are virtually nonluminescent in solution. The goal of this work has
      been to design luminescent forms with practicable emission quantum yields, and
      the focus has been on [Ru(X-T)(dmeb)CN](+) systems, where X-T denotes 2,2':6',2"
      terpyridine bearing substituent X at the 4'-position and dmeb denotes [2,2'
      bipyridine]-4,4'-dicarboxylic acid, dimethyl ester. Results show that varying the
      pi-electron-donating ability of the 4'-X substituent is an effective way to tune
      the energy and lifetime of the charge-transfer (CT) emission. The lifetime
      achieved in a room-temperature, fluid solution is as high as 175 ns, depending on
      the 4'-substituent and the solvent employed because the excited state is very
      polar. That represents a 20-fold improvement in lifetime relative to that of the
      prototype, [Ru(trpy)(bpy)CN](+), one of the earliest examples found to be
      luminescent in a fluid solution. A simple theoretical model proves to be capable
      of rationalizing all the experimental lifetimes. It suggests that, with the dmeb
      ligand available to accept the electron, enhancing the donor ability of the 4'-X
      substituent lowers the energy of the (3)CT state and reduces the likelihood of
      thermally activated decay via a higher-energy d-d state. However, direct
      nonradiative decay to the ground state begins to reduce the excited-state
      lifetime whenever the emission maximum shifts beyond 750 nm. Within those limits,
      there is inevitably a maximal attainable lifetime, regardless of the method of
      tuning. 

PMID- 24128307
TI  - Test-retest reliability of amygdala response to emotional faces.
AB  - In the current study, we evaluated the test-retest reliability of amygdala
      response using an emotional face-matching task that has been widely used to
      examine pathophysiology and treatment mechanisms in psychiatric populations.
      Activation within the fusiform face area (FFA) was also examined. Twenty-seven
      healthy volunteers completed a variation of the face-matching paradigm developed
      by Hariri et al. (2000) at two time points approximately 90 days apart. Estimates
      of test-retest reliability of amygdala response to fearful faces were moderate,
      whereas angry and happy faces showed poor reliability. Test-retest reliability of
      the FFA was moderate to strong, regardless of facial affect. Collectively, these
      findings indicate that the reliability of the BOLD MR signal in the amygdala
      varies substantially by facial affect. Efforts to improve measurement precision,
      enlarge sample sizes, or increase the number of assessment occasions seem
      warranted.

PMID- 24128310
TI  - Peak myocardial acceleration during isovolumic relaxation time predicts the
      occurrence of rehospitalization in chronic heart failure: data from the Daunia
      heart failure registry.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) may be useful in identifying subjects at
      higher risk among patients with chronic heart failure (CHF). The clinical role of
      new developed TDI parameters, however, still needs to be documented. METHODS: A
      total of 113 consecutive patients with CHF enrolled in the Daunia heart failure
      registry underwent echocardiography assessment and were followed prospectively
      for 234 +/- 262 days. Conventional echocardiography and TDI parameters were
      calculated. We also calculated peak myocardial acceleration during isovolumic
      relaxation time (pIVA[r]) derived from TDI (pIVV(r)/AT). RESULTS: Subjects
      readmitted for worsening HF were characterized by lower levels of pIVA(r) (0.8 +/
      0.3 vs. 1.3 +/- 0.5 m/s(2) , P < 0.001). pIVA(r) levels predicted the incidence
      of readmission for worsening HF during follow-up (HR 0.78, 95% confidence
      interval 0.64-0.96, P < 0.05), even after multivariable analysis. The assessment
      of pIVA(r) in addition to left ventricular ejection fraction (LVEF) and E/E'
      provided additional prognostic value (Log Rank P < 0.05). The presence of
      abnormal pIVA(r), LVEF, and E/E' levels identified subjects with a higher risk of
      hospitalization for worsening dyspnea during follow-up than those with 2 abnormal
      marker levels or 0-1 (Log Rank P < 0.05). CONCLUSIONS: Peak myocardial
      acceleration during isovolumic relaxation time may represent an independent
      adjunctive tool for the risk stratification of patients with CHF.

PMID- 24128312
TI  - Mandibular reconstruction using custom-made titanium mesh tray and particulate
      cancellous bone and marrow harvested from bilateral posterior ilia.
AB  - The objective of this study is to evaluate usefulness of mandibular
      reconstructions using a custom-made titanium mesh (Ti-mesh) tray and particulate
      cancellous bone and marrow (PCBM). A consecutive nine patients who underwent
      mandibular reconstruction were enrolled in this study. They were five men and
      four women (mean age: 53.9 years). Virtual reality simulation was performed using
      computer software based on the pre-operative computed tomography data. A 3
      dimensional (3-D) skull model was constructed using a 3-D printer. A tray was
      custom-made from a Ti-mesh sheet bent to adapt to the model. After PCBM
      harvesting from bilateral posterior ilia, the tray was fixed to the host bone.
      New bone formation and configuration of the reconstructed mandible were assessed
      radiologically. Complications were recorded in each patient during the follow-up
      period. Patients, satisfaction with post-operative facial contour was evaluated
      using a visual analogue scale (VAS score, range = 0-100). In six of nine
      patients, excellent new bone formation was recognised and expected results were
      radiologically achieved. Complications occurred in four patients. These
      complications included Ti-mesh fracture, Ti-mesh exposure in the oral cavity, and
      delayed infection. Mean VAS score on patient satisfaction was 77.6. Although the
      data are preliminary, the results suggest that this method is clinically useful.

PMID- 24128313
TI  - Misinformation, disinformation, and violent conflict: from Iraq and the "War on
      Terror" to future threats to peace.
AB  - The dissemination and control of information are indispensable ingredients of
      violent conflict, with all parties involved in a conflict or at war seeking to
      frame the discussion on their own terms. Those attempts at information control
      often involve the dissemination of misinformation or disinformation (i.e.,
      information that is incorrect by accident or intent, respectively). We review the
      way in which misinformation can facilitate violent conflicts and, conversely, how
      the successful refutation of misinformation can contribute to peace. We
      illustrate the relevant cognitive principles by examining two case studies. The
      first, a retrospective case, involves the Iraq War of 2003 and the "War on
      Terror." The second, a prospective case, points to likely future sources of
      conflict arising from climate change and its likely consequences.

PMID- 24128311
TI  - Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial
      antibodies in non-obese diabetic (NOD).B6 (Idd10/Idd18) mice.
AB  - Several epidemiological studies have demonstrated that patients with primary
      biliary cirrhosis (PBC) have a higher incidence of urinary tract infections (UTI)
      and there is significant homology of the immunodominant mitochondrial
      autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2),
      between mammals and bacteria. Previous work has demonstrated that non-obese
      diabetic (NOD).B6 Idd10/Idd18 infected with Novosphingobium aromaticivorans
      developed liver lesions similar to human PBC. It was postulated that the biliary
      disease was dependent upon the presence of the unique N. aro glycosphingolipids
      in activating natural killer T (NK T) cells. To address this issue, we infected
      NOD.B6 Idd10/Idd18 mice with either Escherichia coli, N. aro or use of a
      phosphate-buffered saline (PBS) vehicle control and serially followed animals for
      the appearance of liver pathology and anti-mitochondrial autoantibodies (AMA). Of
      striking importance, the biliary disease of E. coli-infected mice was more severe
      than N. Aro-infected mice and the titre of AMA was higher in E. coli-infected
      mice. Furthermore, the immunopathology did not correlate with the ability of
      bacterial extracts to produce antigen-dependent activation of NK T cells. Our
      data suggest that the unique glycosphingolipids of N. aro are not required for
      the development of autoimmune cholangitis. Importantly, the data highlight the
      clinical significance of E. coli infection in a genetically susceptible host, and
      we suggest that the appearance of autoimmune cholangitis is dependent upon
      molecular mimicry. These data highlight that breach of tolerance to PDC-E2 is
      probably the first event in the natural history of PBC in genetically susceptible
      hosts. 

PMID- 24128314
TI  - Contributions of psychology to war and peace.
AB  - The contributions of American psychologists to war have been substantial and
      responsive to changes in U.S. national security threats and interests for nearly
      100 years. These contributions are identified and discussed for four periods of
      armed conflict: World Wars I and II, the Cold War, and the Global War on Terror.
      In contrast, about 50 years ago, largely in reaction to the threat of nuclear
      war, some psychologists in the United States and around the world broke with the
      tradition of supporting war and began focusing their scholarship and activism on
      the prevention of war and promotion of peace. Today, peace psychology is a
      vibrant area of psychology, with theory and practice aimed at understanding,
      preventing, and mitigating both episodes of organized violence and the pernicious
      worldwide problem of structural violence. The growth, scope, and content of peace
      psychology are reviewed along with contributions to policies that promote peace,
      social justice, and human well-being.

PMID- 24128315
TI  - Bringing science to bear--on peace, not war: elaborating on psychology's
      potential to promote peace.
AB  - We argue that psychological and contextual factors play important roles in
      bringing about, facilitating, and escalating violent conflict. Yet rather than
      conclude that violent conflict is inevitable, we believe psychology's
      contributions can extend beyond understanding the origins and nature of violent
      conflict, to promote nonviolence and peace. In this article, we summarize
      psychological perspectives on the conditions and motivations underlying violent
      conflict. Drawing on this work, we then discuss psychological and contextual
      factors that can mitigate violence and war and promote nonviolence and peace.

PMID- 24128316
TI  - Intergroup contact as a tool for reducing, resolving, and preventing intergroup
      conflict: evidence, limitations, and potential.
AB  - We propose that intergroup contact provides an effective means by which to
      reduce, resolve, and prevent conflict of all kinds, including violent conflict.
      We review the vast literature on the effectiveness of intergroup contact and
      discuss when and how it reduces prejudice. We also discuss key features of
      successful interventions, highlighting examples from conflict zones around the
      world. Rather than accepting, as some scholars do, that conflict is inevitable,
      we argue that intergroup contact, in its various forms, can play a pivotal and
      preemptive role in conflict prevention. We suggest that a blunt application of
      contact theory, particularly when groups are of unequal status, can have some
      unfortunate consequences, and contact interventions can, and should, be designed
      to overcome these pitfalls. We argue that, ultimately, contact is a powerful tool
      that needs to be used alongside other means of conflict reduction, resolution,
      and prevention in order to frame sound public policy and build lasting peace.

PMID- 24128317
TI  - Destined to die but not to wage war: how existential threat can contribute to
      escalation or de-escalation of violent intergroup conflict.
AB  - War means threat to people's lives. Research derived from terror management
      theory (TMT) illustrates that the awareness of death leads people to defend
      cultural ingroups and their worldviews to attain a sense of symbolic immortality
      and thereby buffer existential anxiety. This can result in hostile effects of
      mortality salience (MS), such as derogation of outgroup members, prejudice,
      stereotyping, aggression, and racism, which, in turn, can lead to the escalation
      of violent intergroup conflict and, thus, the escalation of war. Yet, escalation
      of destructive conflict following MS is not automatic. Instead, research on TMT
      suggests that MS does not necessarily result in conflict and intolerance but can
      also foster positive tendencies, such as intergroup fairness or approval of
      pacifism, depending on how existential threat is perceived, whether the need for
      symbolic self-transcendence is satisfied, which social norms are salient, and how
      social situations are interpreted. In the present article, we review current TMT
      research with the aim of reconciling the seemingly contradictory findings of
      hostile and peaceful reactions to reminders of death. We present a terror
      management model of escalation and de-escalation of violent intergroup conflicts,
      which takes into account the interaction between threat salience and features of
      the social situation. We also discuss possible intervention strategies to
      override detrimental consequences of existential threat and argue that war is not
      the inevitable consequence of threat.

PMID- 24128318
TI  - Terrorism--a (self) love story: redirecting the significance quest can end
      violence.
AB  - Jean-Jacques Rousseau's concepts of self-love (amour propre) and love of self
      (amour de soi meme) are applied to the psychology of terrorism. Self-love is
      concern with one's image in the eyes of respected others, members of one's group.
      It denotes one's feeling of personal significance, the sense that one's life has
      meaning in accordance with the values of one's society. Love of self, in
      contrast, is individualistic concern with self-preservation, comfort, safety, and
      the survival of self and loved ones. We suggest that self-love defines a
      motivational force that when awakened arouses the goal of a significance quest.
      When a group perceives itself in conflict with dangerous detractors, its ideology
      may prescribe violence and terrorism against the enemy as a means of significance
      gain that gratifies self-love concerns. This may involve sacrificing one's self
      preservation goals, encapsulated in Rousseau's concept of love of self. The
      foregoing notions afford the integration of diverse quantitative and qualitative
      findings on individuals' road to terrorism and back. Understanding the
      significance quest and the conditions of its constructive fulfillment may be
      crucial to reversing the current tide of global terrorism.

PMID- 24128319
TI  - Building a peaceful society: origins, prevention, and reconciliation after
      genocide and other group violence.
AB  - The 20th century was a century of genocide and other great violence between
      groups within societies. Already at the beginning of the 21st century, there have
      been mass killings, civil wars, violent conflict, and terrorism. This article
      summarizes influences that tend to lead to intense group violence. It then
      considers prevention, stressing early prevention--and reconciliation as an aspect
      of prevention--and focusing on central principles and practices. The principles
      include developing positive orientations to previously devalued groups; healing
      from past victimization and promoting altruism born of suffering; moderating
      respect for authority; creating constructive ideologies; promoting understanding
      of the origins of violence, its impact, and avenues to prevention; promoting
      truth, justice, and a shared history; and raising inclusively caring, morally
      courageous children. Practices related to all of these are also discussed. The
      article stresses the role of progressive change, that is, of psychological,
      behavioral, and social evolution, in both extreme violence and positive relations
      between groups; the role of passive bystanders in the unfolding of violence; and
      the role of active bystandership in the prevention of violence, in the promotion
      of reconciliation, and in the development of harmonious societies. It emphasizes
      psychological processes but notes the importance of creating societal
      institutions. The author cites findings from both laboratory research and case
      studies, reviews interventions and their evaluation in Rwanda, and points to the
      need for further research.

PMID- 24128320
TI  - Contributions of positive psychology to peace: toward global well-being and
      resilience.
AB  - In this article, we analyze the relationship between positive psychology and
      peace psychology. We discuss how positive emotions, engagement, meaning, personal
      well-being, and resilience may impact peace at different levels, ranging from the
      personal and interpersonal to community, national, and global peace. First, we
      argue that an individual's positive experiences, personal well-being, and
      personal resilience, as defined in current positive psychology, may in fact
      contribute to personal and interpersonal peace but can also entail detrimental
      consequences for other individuals, communities, and nations. Second, we describe
      how peace psychology contains traces of positive psychology, especially with its
      focus on the pursuit of social justice. Third, reviewing and extending the
      concept of community resilience, we outline directions for further conceptual and
      empirical work in positive psychology inspired by peace psychology. Such work
      would do well to transcend positive psychology's current bias toward
      individualism and nationalism and to conceptualize well-being and resilience at
      the level of the "global community." This extended "positive peace psychology"
      perspective would have important implications for our understanding of how to
      overcome oppression and work toward global peace.

PMID- 24128323
TI  - Bullous pemphigoid and dermatitis herpetiformis association: a genetic
      predisposition.

PMID- 24128322
TI  - Influence of zoledronic acid on disseminated tumor cells in bone marrow and
      survival: results of a prospective clinical trial.
AB  - BACKGROUND: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of
      breast cancer patients is associated with reduced clinical outcome.
      Bisphosphonate treatment was shown to eradicate DTC from BM in several studies.
      This controlled randomized open-label multi-center study aimed to investigate the
      influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients
      (Clinical Trial Registration Number: NCT00172068). METHODS: Patients with primary
      breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL
      plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n =
      46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using
      the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC
      numbers at 12 months and 24 months versus baseline, as well as patient outcomes
      were evaluated. RESULTS: 86 patients could be included into survival analysis
      (median follow-up: 88 months, range: 8-108 mths). Patients in the control group
      were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%,
      p = 0.106). 15% of patients in the control group presented with relapse whereas
      only 8% of ZOL group patients developed metastatic or recurrent disease during
      follow-up (p = 0.205). At 24 months, 16% of patients from the control group were
      still DTC positive, whereas all patients treated with ZOL became DTC negative (p
      = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had
      significantly shorter overall survival (p = 0.011). CONCLUSIONS: Bisphosphonate
      therapy contributes to eradication of disseminated tumor cells. The positive
      influence of bisphosphonates on survival in the adjuvant setting may be due to
      their effects on DTC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal
      Residual Disease in the Bone Marrow (MRD-1)].

PMID- 24128324
TI  - Experimental characterization of C-X...Y-C (X = Br, I; Y = F, Cl) halogen-halogen
      bonds.
AB  - Using FTIR and Raman spectroscopy, we investigated the formation of halogen
      bonded complexes of the trifluorohalomethanes CF3Cl, CF3Br, and CF3I with the
      halomethanes CH3F and CH3Cl and the haloethanes C2H5F and C2H5Cl dissolved in
      liquid krypton. For CF3Br and CF3I, evidence was found for the formation of C
      X...F and C-X...Cl halogen bonded 1:1 complexes. Using spectra recorded at
      different temperatures, we determined the complexation enthalpies for the
      complexes to be -7.0(3) kJ mol(-1) for CF3Br.CH3F, -7.6(1) kJ mol(-1) for
      CF3I.CH3F, -5.9(2) kJ mol(-1) for CF3Br.CH3Cl, -8.3(3) kJ mol(-1) for CF3I.CH3Cl,
      -7.1(1) kJ mol(-1) for CF3Br.C2H5F, -8.7(2) kJ mol(-1) for CF3I.C2H5F, -6.5(2) kJ
      mol(-1) for CF3Br.C2H5Cl, and -8.8(3) kJ mol(-1) for CF3I.C2H5Cl. For all halogen
      bonded complexes with a fluorine-electron donor, a blue shift ranging from +0.6
      to +1.5 cm(-1) was observed for the C-X stretching mode. The results from the
      cyrospectroscopic study are compared with ab initio calculations at the MP2/aug
      cc-pVDZ(-PP) level. 

PMID- 24128325
TI  - Low birth weight: causes and consequences.
AB  - During our phylogenetic evolution we have selected genes, the so called thrifty
      genes, that can help to maximize the amount of energy stored from every consumed
      calorie. An imbalance in the amount of stored calories can lead to many diseases.
      In the early 80's the distinguished English epidemiologist David Barker,
      formulated a hypothesis suggesting that many events that occur during the
      intrauterine life and early in infancy can influence the occurrence of many
      diseases that will develop in adulthood. This theory proposes that under
      nutrition and other insult or adverse stimulus in utero and during infancy can
      permanently change the body's structure, physiology and metabolism. The lasting
      or lifelong effects of under-nutrition will depend on the period in the
      development at which it occurs. The clues that led Barker to his conclusions
      started to be discovered when he was studying the temporal trends in the
      incidence of ischemic heart disease in England and Wales. Examining data found in
      The Hertfordshire records, collected in the beginning of the last century, he
      found that the rates of mortality by ischemic heart disease was much higher in
      children born in less affluent counties and mostly in those with low birth
      weight. After his initial findings a myriad of diseases have been found to be
      linked to low birth weight and under-nutrition in utero and in the neonatal
      period. These diseases were then nominated adult diseases with fetal origin.
      Epidemiological studies that led to these findings suggest that in utero and
      early postnatal life have critical importance for long-term programming of health
      and disease, opening unique chances for primary prevention of chronic diseases. 

PMID- 24128327
TI  - Parental separation/divorce in childhood and partnership outcomes at age 30.
AB  - BACKGROUND: Previous research has found that children exposed to
      separation/divorce may also experience relationship problems in adulthood. The
      aim of this investigation was to examine this issue in a birth cohort of over 900
      New Zealand children studied to age 30. METHODS: Data were gathered over the
      course of the Christchurch Health and Development Study (CHDS). The CHDS is a 30
      year longitudinal study of a birth cohort of 1265 children born in Christchurch
      (NZ) in 1977. The data collected included the following: (a) timing and number of
      parental separations and divorces from birth to 15 years; (b) partnership
      outcomes (16-30 years) of the number of cohabiting/marriage partnerships;
      positive partner relations; negative partner relations; partner
      adjustment/conduct problems; and interpartner violence victimization and
      perpetration; and (c) potential covariate factors. RESULTS: Study findings showed
      the presence of significant associations between childhood parental
      separations/divorces and number of cohabiting/marriage partnerships (16-30 years)
      (p < .001), negative partner relations (p = .021), extent of partner
      adjustment/conduct problems (p < .001), and perpetration of interpartner violence
      (p = .018). Childhood parental separation/divorce explained less than 2.5% of the
      variance in partnership outcomes. These associations were explained statistically
      by a series of covariate factors associated with childhood parental
      separation/divorce including parental history of illicit drug use, childhood
      sexual abuse, childhood conduct problems (7-9 years), interparental conflict and
      violence, childhood physical punishment/maltreatment, family socio-economic
      status at the child's birth, and parental history of criminality. Tests of gender
      interaction showed that the effect of childhood parental separations/divorces may
      be the same for males and females. Analysis of the number of childhood parental
      separations/divorces experienced into three age groups (birth to 5, 5-10 years
      and 10-15 years) yielded similar results. CONCLUSIONS: These findings suggest
      that the general associations between childhood parental separation/divorce and
      partner relationships in adulthood reflect the consequences of various contextual
      factors that are associated with childhood parental separation.

PMID- 24128326
TI  - Sporadic naturally occurring melanoma in dogs as a preclinical model for human
      melanoma.
AB  - Melanoma represents a significant malignancy in humans and dogs. Different from
      genetically engineered models, sporadic canine melanocytic neoplasms share
      several characteristics with human disease that could make dogs a more relevant
      preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur
      in the oral cavity, with a subset having intra-epithelial malignant melanocytes
      mimicking the in situ component of human mucosal melanoma. The spectrum of canine
      melanocytic neoplasia includes benign lesions with some analogy to nevi, as well
      as invasive primary melanoma, and widespread metastasis. Growing evidence of
      distinct subtypes in humans, differing in somatic and predisposing germ-line
      genetic alterations, cell of origin, epidemiology, relationship to ultraviolet
      radiation and progression from benign to malignant tumors, may also exist in
      dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit
      mutations uncommonly, compared with human cutaneous melanomas, although both
      species share AKT and MAPK signaling activation. We conclude that there is
      significant overlap in the clinical and histopathological features of canine and
      human mucosal melanomas. This represents opportunity to explore canine oral
      cavity melanoma as a preclinical model. 

PMID- 24128328
TI  - A beta-glucuronosyltransferase from Arabidopsis thaliana involved in biosynthesis
      of type II arabinogalactan has a role in cell elongation during seedling growth.
AB  - We have characterized a beta-glucuronosyltransferase (AtGlcAT14A) from
      Arabidopsis thaliana that is involved in the biosynthesis of type II
      arabinogalactan (AG). This enzyme belongs to the Carbohydrate Active Enzyme
      database glycosyltransferase family 14 (GT14). The protein was localized to the
      Golgi apparatus when transiently expressed in Nicotiana benthamiana. The soluble
      catalytic domain expressed in Pichia pastoris transferred glucuronic acid (GlcA)
      to beta-1,6-galactooligosaccharides with degrees of polymerization (DP) ranging
      from 3-11, and to beta-1,3-galactooligosaccharides of DP5 and 7, indicating that
      the enzyme is a glucuronosyltransferase that modifies both the beta-1,6- and beta
      1,3-galactan present in type II AG. Two allelic T-DNA insertion mutant lines
      showed 20-35% enhanced cell elongation during seedling growth compared to wild
      type. Analyses of AG isolated from the mutants revealed a reduction of GlcA
      substitution on Gal-beta-1,6-Gal and beta-1,3-Gal, indicating an in vivo role of
      AtGlcAT14A in synthesis of those structures in type II AG. Moreover, a relative
      increase in the levels of 3-, 6- and 3,6-linked galactose (Gal) and reduced
      levels of 3-, 2- and 2,5-linked arabinose (Ara) were seen, suggesting that the
      mutation in AtGlcAT14A results in a relative increase of the longer and branched
      beta-1,3- and beta-1,6-galactans. This increase of galactosylation in the mutants
      is most likely caused by increased availability of the O6 position of Gal, which
      is a shared acceptor site for AtGlcAT14A and galactosyltransferases in synthesis
      of type II AG, and thus addition of GlcA may terminate Gal chain extension. We
      discuss a role for the glucuronosyltransferase in the biosynthesis of type II AG,
      with a biological role during seedling growth. 

PMID- 24128329
TI  - A sequential sampling account of response bias and speed-accuracy tradeoffs in a
      conflict detection task.
AB  - Signal Detection Theory (SDT; Green & Swets, 1966) is a popular tool for
      understanding decision making. However, it does not account for the time taken to
      make a decision, nor why response bias might change over time. Sequential
      sampling models provide a way of accounting for speed-accuracy trade-offs and
      response bias shifts. In this study, we test the validity of a sequential
      sampling model of conflict detection in a simulated air traffic control task by
      assessing whether two of its key parameters respond to experimental manipulations
      in a theoretically consistent way. Through experimental instructions, we
      manipulated participants' response bias and the relative speed or accuracy of
      their responses. The sequential sampling model was able to replicate the trends
      in the conflict responses as well as response time across all conditions.
      Consistent with our predictions, manipulating response bias was associated
      primarily with changes in the model's Criterion parameter, whereas manipulating
      speed-accuracy instructions was associated with changes in the Threshold
      parameter. The success of the model in replicating the human data suggests we can
      use the parameters of the model to gain an insight into the underlying response
      bias and speed-accuracy preferences common to dynamic decision-making tasks.

PMID- 24128330
TI  - Incremental detection rate of prostate cancer by real-time elastography targeted
      biopsies in combination with a conventional 10-core biopsy in 1024 consecutive
      patients.
AB  - OBJECTIVE: To quantify the incremental detection rate (DR) of a targeted biopsy
      in addition to a randomized 10-core biopsy. PATIENTS AND METHODS: This
      retrospective study analysed 1024 patients who consecutively underwent a four
      core real-time elastography (RTE) targeted biopsies in addition to a randomized
      10-core transrectal ultrasonography (TRUS)-guided biopsy in a primary or rebiopsy
      setting. The overall DR, the DR of a 10-core randomized, RTE targeted biopsy and
      the incremental DR were calculated. RESULTS: Overall, randomized and RTE targeted
      biopsy DRs (for the combination, the 10-core and the four-core RTE biopsy scheme)
      were 46.2% (n = 473), 39.1% (n = 400) and 29.0% (n = 297), respectively. Four
      core RTE targeted biopsies detected an additional 73 patients not detected by the
      10-core randomized biopsies (increase in the overall DR of 7.1%). This
      represented a relative increase in DR of 18.3%. The incremental DR was better in
      rebiopsy patients (24.8%) than in patients having their first biopsy (14.7%).
      Within all patients diagnosed by RTE targeted biopsy only, 34 patients harboured
      significant Gleason 4 or 5 prostate cancer (PCa), diagnosed by four-core RTE
      biopsy only. Moreover, PCa with a Gleason grade of 4 or 5 was detected by four
      core RTE biopsies in 30 patients, who showed low-grade PCa <= Gleason 3 only in
      the systematic 10-core biopsy. CONCLUSIONS: Real-time elastography targeted
      biopsy seems to be an appropriate method for increasing the DR of PCa.
      Nevertheless, RTE targeted biopsies missed a high proportion of patients with PCa
      and should therefore be considered as an addition to randomized biopsies.

PMID- 24128332
TI  - Autotaxin as a novel, tissue-remodeling-related factor in regressing corpora
      lutea of cycling rats.
AB  - Autotaxin (ATX) generates lysophosphatidic acid (LPA) from glycerophospholipid
      via lysophospholipase D (lysoPLD) activity in cooperation with phospholipase A.
      We studied its expression and possible functional roles in the ovary of
      nonfertile cycling rats. Immunohistochemistry revealed that ATX was located
      predominantly in luteal steroidogenic cells of corpora lutea (CL), but not in any
      follicles. ATX expression was modest in the newest generation of CL and augmented
      in older generations undergoing structural regression. ATX expression in the
      whole ovary and lysoPLD activity in circulating blood did not alter during the
      estrous cycle. Among the LPA receptors examined (LPA1-4 ), LPA4 was densely
      present on migratory cells, probably phagocytes, at degenerative foci within
      regressing CL. Bolus administration of anti-ATX IgG or LPA into ovarian bursa in
      vivo had little effect on the apoptotic cell death of luteal cells, as evaluated
      by cleaved caspase 3 expression, but led to altered numbers of neutrophils and
      macrophages in regressing CL, as evaluated by immunological detection of each
      cell marker. These treatments, together with bromodeoxy uridine, revealed a
      stimulatory effect of the ATX/LPA pathway on fibroblast proliferation in
      regressing CL. The results indicate that ATX is increasingly expressed by
      structurally regressing CL and has definite local action on phagocyte recruitment
      and fibroblast proliferation which are responsible for tissue remodeling. 

PMID- 24128333
TI  - Debate on HES safety is important, but must be based on facts.
AB  - The Scandinavian Starch for Severe Sepsis / Septic Shock (6S) trial showed that
      hydroxyethyl starch was harmful compared to Ringer's acetate in patients with
      severe sepsis when used according to clinical practice and in alignment with the
      recommendations by the manufactures and authorities. The different interpretation
      by Chapell and Jacob's rely on misreading of the trial publication and is not
      supported by the trial data. Several hypotheses may be made regarding less
      harmful ways of using HES in critically ill patients, but clinicians, guideline
      committee members and authorities need to acknowledge that such safer ways have
      not yet been identified. 

PMID- 24128334
TI  - In vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs.
AB  - BACKGROUND: Confocal endomicroscopy (CEM) is an endoscopic technology that
      permits in vivo cellular and subcellular imaging of the gastrointestinal mucosa.
      OBJECTIVE: To determine the feasibility of CEM to evaluate small intestinal
      mucosal topologic morphology in dogs and to characterize the appearance in
      healthy dogs. ANIMALS: Fourteen clinically healthy research colony dogs. METHODS:
      Experimental study. Dogs were anesthetized for standard endoscopic evaluation of
      the small intestine followed by CEM. Two fluorophores were used to provide
      contrast: fluorescein (10% solution, 15 mg/kg IV) before administration of
      topical acriflavine (0.05% solution) via an endoscopy spray catheter. A minimum
      of 5 sites within the small intestine were assessed and at each location,
      sequential adjustment of imaging depth allowed collection of a three-dimensional
      volume equivalent to an 'optical biopsy'. CEM-guided pinch biopsies were obtained
      for histologic examination. RESULTS: CEM provided high-quality in vivo cellular
      and subcellular images. Intravenous administration of fluorescein provided
      sufficient contrast to allow assessment of the vasculature, cellular cytoplasmic
      features and goblet cell numbers, and distribution. Topical application of
      acriflavine preferentially stained cellular nucleic acids, allowing evaluation of
      nuclear morphology. Quality of captured images was occasionally affected by
      motion artifact, but improved with operator experience. CONCLUSION AND CLINICAL
      IMPORTANCE: CEM provides in vivo images that allow for cellular and subcellular
      assessment of intestinal mucosal morphology during endoscopy. This has
      implications for aiding in vivo diagnosis of gastrointestinal disease.

PMID- 24128335
TI  - Use of cannula ileostomy to protect a low colorectal anastomosis in patients
      having preoperative neoadjuvant chemoradiotherapy.
AB  - AIM: This study evaluated the efficacy and safety of ileal diversion, using a
      tracheal cannula, to protect from a low colorectal anastomosis in patients
      treated with neoadjuvant chemoradiotherapy. METHOD: Fifty patients who presented
      with rectal cancer and who had accepted neoadjuvant chemoradiotherapy were
      included. All underwent a low anterior resection with ileal diversion by either
      tracheal cannula ileostomy (n = 28) or conventional loop ileostomy (n = 22).
      Demographics, clinical features and operation data were recorded. RESULTS: Two
      patients developed anastomotic dehiscence after completion of the cannula
      ileostomy but neither patient required any further operation. There was no
      difference in anastomotic dehiscence, peritonitis or requirement for further
      surgery in patients treated with cannula ileostomy and loop ileostomy.
      CONCLUSION: Cannula ileostomy is a safe, quick, effective and convenient means of
      intestinal diversion after low anterior resection. Its obvious advantage over
      loop ileostomy is a reduced overall hospital stay and avoidance of the need to
      close the stoma.

PMID- 24128336
TI  - The influence of vitamin A status on iron-deficiency anaemia in anaemic
      adolescent schoolgirls in Myanmar.
AB  - OBJECTIVE: The present study was conducted to investigate reasons for the high
      prevalence of anaemia among adolescent schoolgirls and to elucidate the role of
      vitamin A in contributing to Fe-deficiency anaemia (IDA). DESIGN: Among 1269
      schoolgirls who were previously screened for anaemia (Hb < 120 g/l), 391 anaemic
      girls were further assessed for Fe, vitamin A and subclinical inflammation
      status. Fe and vitamin A indicators were corrected for inflammation and were
      compared in the Fe-deficient and non-deficient groups as well as between those
      with and without inflammation. Logistic regression was done to determine whether
      vitamin A status and subclinical inflammation were risk factors for Fe
      deficiency. The differences in Fe status among tertiles of vitamin A
      concentrations were assessed using ANOVA. SETTING: Myanmar. SUBJECTS: Adolescent
      schoolgirls (n 391). RESULTS: One-third of the anaemia (30.4%) was IDA.
      Prevalence of low vitamin A status (serum retinol <1.05 MUmol/l) was 31.5%. Fe
      and vitamin A status were significantly different between the IDA and non-IDA
      groups and also based on their inflammation status. Logistic regression showed
      that low vitamin A status was a significant predictor for being Fe deficient (OR
      = 1.81; 95% CI 1.03, 3.19 and OR = 2.31; 1.31, 4.07 in the middle (1.056-1.298
      MUmol/l) and low (<=1.056 MUmol/l) vitamin A tertiles, respectively). ANOVA
      showed that better Fe status was associated with a higher concentration of serum
      retinol but only in IDA. CONCLUSIONS: Fe deficiency was not the main cause of
      anaemia in the present population. The role of vitamin A as well as other
      micronutrients should be taken into account in addressing the problem of anaemia.

PMID- 24128337
TI  - Copper sulfide nanocrystals with tunable composition by reduction of covellite
      nanocrystals with Cu+ ions.
AB  - Platelet-shaped copper sulfide nanocrystals (NCs) with tunable Cu stoichiometry
      were prepared from Cu-rich covellite (Cu1.1S) nanoplates through their reaction
      with a Cu(I) complex ([Cu(CH3CN)4]PF6) at room temperature. Starting from a
      common sample, by this approach it is possible to access a range of compositions
      in these NCs, varying from Cu1.1S up to Cu2S, each characterized by a different
      optical response: from the metallic covellite, with a high density of free
      carriers and strong localized surface plasmon resonance (LSPR), up to Cu2S NCs
      with no LSPR. In all these NCs the valency of Cu in the lattice stays always
      close to +1, while the average -1 valency of S in covellite gradually evolves to 
      2 with increasing Cu content; i.e., sulfur is progressively reduced. The addition
      of copper to the starting covellite NCs is similar to the intercalation of metal
      species in layered transition metal dichalcogenides (TMDCs); i.e., the chalcogen
      chalcogen bonds holding the layers are progressively broken to make room for the
      intercalated metals, while their overall anion sublattice does not change much.
      However, differently from the TMDCs, the intercalation in covellite NCs is
      sustained by a change in the redox state of the anion framework. Furthermore, the
      amount of Cu incorporated in the NCs upon reaction is associated with the
      formation of an equimolar amount of Cu(II) species in solution. Therefore, the
      reaction scheme can be written as: Cu1.1S + 2gammaCu(I) -> Cu1.1+gammaS +
      gammaCu(II). 

PMID- 24128341
TI  - Light-enhanced displacement of methyl acrylate from iron carbonyl: investigation
      of the reactive intermediate via rapid-scan Fourier transform infrared and
      computational studies.
AB  - The thermal displacement of methyl acrylate from Fe(CO)4(eta(2)-CH2=CHCOOMe) by
      phosphine ligands is a relatively slow reaction requiring several hours at
      elevated temperatures. In the present study, it is observed that photolysis of
      the tetracarbonyl complex with UV light activates the process such that the
      reaction is complete within a few seconds. This rate enhancement is due to the
      formation of an intermediate eta(4) complex where the organic C=O and C=C units
      of methyl acrylate occupy axial and equatorial coordination sites on the Fe
      center, respectively, following photochemical CO loss. The displacement of methyl
      acrylate from this photolytically generated intermediate is facile with a
      remarkably low barrier of 8.7 kcal/mol. Density functional theory calculations
      support these experimental observations. 

PMID- 24128338
TI  - Detecting adaptive trait loci in nonmodel systems: divergence or admixture
      mapping?
AB  - Mapping adaptive trait loci (ATL) underlying ecological divergence is an
      essential step towards understanding the processes that generate phenotypic
      diversity. Technological advances have made it possible to sequence exomes in
      nonmodel systems, providing an efficient means of analysing functional genetic
      variants. Divergence scans of genetic markers for outlier loci, or 'divergence
      mapping', have been used to map locally adapted genes, but this approach is
      likely to be underpowered when background divergence is elevated. Genotype
      phenotype association tests in admixed populations, or 'admixture mapping', may
      provide a useful approach for mapping locally adapted loci when neutral
      divergence is high. To determine the power and limits of divergence mapping, we
      simulated exomes containing a single ATL across two parental populations of
      varying neutral divergence, estimated divergence and quantified the power to
      identify the ATL. We found that divergence mapping had very high power when
      background FST is <0.2, but decreased dramatically above this level. To evaluate
      the utility of admixture mapping, we simulated exomes from admixed populations,
      then simulated phenotypes, conducted genotype-phenotype association tests and
      found that even two generations of random mating after admixture could provide
      high mapping power in scenarios where pure divergence mapping was ineffective
      (FST = 0.35). Moreover, admixture mapping had high power across all levels of
      divergence after 20 generations since admixture. Together with high-throughput
      exome sequencing, admixture mapping could be used to map ATL in systems such as
      Heliconius butterflies or Gryllus crickets when experimental design and
      analytical approach are chosen accordingly.

PMID- 24128339
TI  - Differences in physician and patient perceptions about insulin therapy for
      management of type 2 diabetes: the DAWN Japan study.
AB  - OBJECTIVE: To better understand patient resistance to initiation of insulin
      therapy, this study examined the perception gap concerning initiation of insulin
      therapy between individuals with type 2 diabetes and their physicians by using
      data from the DAWN Japan study. METHODS: The DAWN Japan study is a multi-center,
      questionnaire-based survey, conducted between 2004-2005. Patients recommended to
      start insulin therapy (n = 148) answered a questionnaire by rating degree of
      agreement with 16 statements concerning insulin therapy on a 5-point scale (1:
      strongly disagree to 5: strongly agree). Ratings of 1 and 2 were categorized as
      'disagree' with a statement, and 3, 4, and 5 as 'agree'. Their attending
      physicians (n = 68) selected statements which could be associated with patient's
      concerns about insulin therapy. RESULTS: Nearly all the patients agreed with the
      statements 'I don't want to inject myself for the rest of my life' (95%), and 'I
      don't want to be bothered with doing injections' (90%); fewer than half agreed
      with 'My friendships may suffer' (46%), and 'I don't understand why insulin is
      necessary for me' (45%). Estimation by the physicians and the actual perceptions
      patients reported differed significantly for 13 statements. Physicians seemed to
      particularly under-estimate the impact associated with social aspects of insulin
      use (e.g., 'I don't want to be different from others', 55% patients vs 7%
      physicians). On the contrary, the statement 'Injections are painful' was the only
      concern over-estimated by the physicians. CONCLUSIONS: It was demonstrated that
      differences in perceptions regarding insulin therapy exist between physicians and
      patients, particularly in terms of social impacts. The data, obtained in 2004,
      may not precisely reflect the present situation, but still represents a barrier
      to insulin therapy widely held by patients and physicians. These results suggest
      that appropriate understanding of patients' concerns about insulin therapy is
      important to encourage timely insulin initiation.

PMID- 24128342
TI  - Identification of a binding element for the cytoplasmic regulator FROUNT in the
      membrane-proximal C-terminal region of chemokine receptors CCR2 and CCR5.
AB  - Chemokine receptors mediate the migration of leucocytes during inflammation. The
      cytoplasmic protein FROUNT binds to chemokine receptors CCR2 [chemokine (C-C
      motif) receptor 2] and CCR5, and amplifies chemotactic signals in leucocytes.
      Although the interaction between FROUNT and chemokine receptors is important for
      accurate chemotaxis, the interaction mechanism has not been elucidated. In the
      present study we identified a 16-amino-acid sequence responsible for high
      affinity binding of FROUNT at the membrane-proximal C-terminal intracellular
      region of CCR2 (CCR2 Pro-C) by yeast two-hybrid analysis. Synthesized peptides
      corresponding to the CCR2 Pro-C sequence directly interacted with FROUNT in
      vitro. CCR2 Pro-C was predicted to form an amphipathic helix structure. Residues
      on the hydrophobic side are completely conserved among FROUNT-binding receptors,
      suggesting that the hydrophobic side is the responsible element for FROUNT
      binding. The L316T mutation to the hydrophobic side of the predicted helix
      decreased the affinity for FROUNT. Co-immunoprecipitation assays revealed that
      the CCR2 L316T mutation diminished the interaction between FROUNT and full-length
      CCR2 in cells. Furthermore, this mutation impaired the ability of the receptor to
      mediate chemotaxis. These findings provide the first description of the
      functional binding element in helix 8 of CCR2 for the cytosolic regulator FROUNT
      that mediates chemotactic signalling.

PMID- 24128343
TI  - Less small airway dysfunction in asymptomatic bronchial hyperresponsiveness than
      in asthma.
AB  - BACKGROUND: Bronchial hyperresponsiveness (BHR) can be present in subjects
      without any respiratory symptoms. Little is known about the role of the small
      airways in asymptomatic subjects with BHR. METHODS: We investigated small airway
      function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea
      scores at baseline and during a methacholine provocation test in 15 subjects with
      asymptomatic BHR, 15 asthma patients, and 15 healthy controls. RESULTS: At
      baseline, small airway function (R5 -R20 and X5 ) was comparable between subjects
      with asymptomatic BHR and healthy controls, whereas asthma patients showed small
      airway dysfunction as reflected by higher R5 -R20 and lower X5 values. During
      methacholine provocation, small airway dysfunction was more severe in asthma
      patients than in subjects with asymptomatic BHR. Interestingly, a higher increase
      in small airway dysfunction during methacholine provocation was associated with a
      higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not
      in asthma patients. CONCLUSION: Subjects with asymptomatic BHR may experience
      fewer symptoms in daily life because they have less small airway dysfunction.

PMID- 24128345
TI  - Evidence of unlimited-capacity surface completion.
AB  - Capacity limitations of perceptual surface completion were assessed using a
      simultaneous-sequential method. Observers searched among multiple surfaces
      requiring perceptual completion in front of other objects (modal completion) or
      behind other objects (amodal completion). In the simultaneous condition, all
      surfaces were presented at once, whereas in the sequential condition, they
      appeared in subsets of 2 at a time. For both modal and amodal surface completion,
      performance was as good in the simultaneous condition as in the sequential
      condition, indicating that surface completion unfolds independently for multiple
      surfaces across the visual field (i.e., has unlimited capacity). We confirmed
      this was due to the formation of surfaces defined by the pacmen inducers, and not
      simply to the detection of individual features of the pacmen inducers. These
      results provide evidence that surface-completion processes can be engaged and
      unfold independently for multiple surfaces across the visual field. In other
      words, surface completion can occur through unlimited-capacity processes. These
      results contribute to a developing understanding of capacity limitations in
      perceptual processing more generally.

PMID- 24128344
TI  - Sex and inflammation in respiratory diseases: a clinical viewpoint.
AB  - This review discusses sex differences in the prognosis of acute or chronic
      inflammatory diseases. The consequences of severe inflammation vary in relation
      to sex, depending on illness duration. In the majority of acute diseases, males
      present higher mortality rates, whereas continuous chronic inflammation
      associated with tissue damage is more deleterious in females. The recruitment of
      cells, along with its clinical expression, is more significant in females, as
      reflected by higher inflammatory markers. Given that estrogens or androgens are
      known to modulate inflammation, their different levels in males and females
      cannot account for the sexual dimorphism observed in humans and animals from
      birth to death with regard to inflammation. Numerous studies evaluated receptors,
      cytokine production, and clinical outcomes in both animals and humans, revealing
      that estrogens clearly modulate the immune response, but the results are
      contradictory and difficult to link to hormone concentrations. Even in
      prepubescent children, the presentation of acute pneumonia or chronic diseases
      mimics the adult pattern. Several genes located on the X chromosome have been
      shown to encode molecules involved in inflammation. Moreover, 10% to 15% of the
      genes from silenced X chromosome may escape inhibition. Females are also a mosaic
      of cells with genes from either paternal or maternal X chromosome. Therefore,
      polymorphism of X-linked genes would result in the presence of two cell
      populations with distinct regulatory arsenals, providing females with greater
      diversity to fight against infectious challenges, in comparison with the uniform
      cell populations in hemizygous males. The similarities observed between males and
      Turner syndrome patients using an endotoxin stimulation model support the
      difference in gene expression between monosomy and disomy for the X chromosome.
      Considering the enhanced inflammation in females, cytokine production may be
      assumed to be higher in females than males. Even if all results are not clear
      cut, nonetheless, many studies have reported higher cytokine levels in both male
      humans and animals than in females. High IL-6 levels in males correlated with
      poorer prognosis and shorter longevity. A sound understanding of the basic
      regulatory mechanisms responsible for these gender differences may lead to new
      therapeutic targets. 

PMID- 24128346
TI  - The interaction between stimulus-driven and goal-driven orienting as revealed by
      eye movements.
AB  - It is generally agreed that attention can be captured in a stimulus-driven or in
      a goal-driven fashion. In studies that investigated both types of capture, the
      effects on mean manual response time (reaction time [RT]) are generally additive,
      suggesting two independent underlying processes. However, potential interactions
      between the two types of capture may fail to be expressed in manual RT, as it
      likely reflects multiple processing steps. Here we measured saccadic eye
      movements along with manual responses. Participants searched a target display for
      a red letter. To assess contingent capture, this display was preceded by an
      irrelevant red cue. To assess stimulus-driven capture, the target display could
      be accompanied by the simultaneous onset of an irrelevant new object. At the
      level of eye movements, the results showed strong interactions between cue
      validity and onset presence on the spatiotemporal trajectories of the saccades.
      However, at the level of manual responses, these effects cancelled out, leading
      to additive effects on mean RT. We conclude that both types of capture influence
      a shared spatial orienting mechanism and we provide a descriptive computational
      model of their dynamics.

PMID- 24128347
TI  - The effects of statins on the mevalonic acid pathway in recombinant yeast strains
      expressing human HMG-CoA reductase.
AB  - BACKGROUND: The yeast Saccharomyces cerevisiae can be a useful model for studying
      cellular mechanisms related to sterol synthesis in humans due to the high
      similarity of the mevalonate pathway between these organisms. This metabolic
      pathway plays a key role in multiple cellular processes by synthesizing sterol
      and nonsterol isoprenoids. Statins are well-known inhibitors of 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGR), the key enzyme of the cholesterol synthesis
      pathway. However, the effects of statins extend beyond their cholesterol-lowering
      action, since inhibition of HMGR decreases the synthesis of all products
      downstream in the mevalonate pathway. Using transgenic yeast expressing human
      HMGR or either yeast HMGR isoenzyme we studied the effects of simvastatin,
      atorvastatin, fluvastatin and rosuvastatin on the cell metabolism. RESULTS:
      Statins decreased sterol pools, prominently reducing sterol precursors content
      while only moderately lowering ergosterol level. Expression of genes encoding
      enzymes involved in sterol biosynthesis was induced, while genes from nonsterol
      isoprenoid pathways, such as coenzyme Q and dolichol biosynthesis or protein
      prenylation, were diversely affected by statin treatment. Statins increased the
      level of human HMGR protein substantially and only slightly affected the levels
      of Rer2 and Coq3 proteins involved in non-sterol isoprenoid biosynthesis.
      CONCLUSION: Statins influence the sterol pool, gene expression and protein levels
      of enzymes from the sterol and nonsterol isoprenoid biosynthesis branches and
      this effect depends on the type of statin administered. Our model system is a
      cheap and convenient tool for characterizing individual statins or screening for
      novel ones, and could also be helpful in individualized selection of the most
      efficient HMGR inhibitors leading to the best response and minimizing serious
      side effects.

PMID- 24128348
TI  - Chicken single-chain antibody fused to alkaline phosphatase detects Aspergillus
      pathogens and their presence in natural samples by direct sandwich enzyme-linked
      immunosorbent assay.
AB  - A sensitive and specific analytical method to detect ubiquitous aflatoxigenic
      Aspergillus pathogens is essential for monitoring and controlling aflatoxins.
      Four highly reactive chicken single-chain variable fragments (scFvs) against
      soluble cell wall proteins (SCWPs) from Aspergillus flavus were isolated by phage
      display. The scFv antibody AfSA4 displayed the highest activity toward both A.
      flavus and A. parasiticus and specifically recognized a surface target of their
      cell walls as revealed by immunofluorescence localization. Molecular modeling
      revealed a unique compact motif on the antibody surface mainly involving L-CDR2
      and H-CDR3. As measured by surface plasmon resonance, AfSA4 fused to alkaline
      phosphatase had a higher binding capability and 6-fold higher affinity compared
      with AfSA4 alone. Immunoblot analyses showed that the fusion had good binding
      capacity to SCWP components from the two fungal species. Direct sandwich enzyme
      linked immunosorbent assays with mouse antiaspergillus monoclonal antibody mAb2A8
      generated in parallel as a capture antibody revealed that the detection limit of
      the two fungi was as low as 10(-3) MUg/mL, 1000-fold more sensitive than that
      reported previously (1 MUg/mL). The fusion protein was able to detect fungal
      concentrations below 1 MUg/g of maize and peanut grains in both artificially and
      naturally contaminated samples, with at least 10-fold more sensitivity than that
      reported (10 MUg/g) thus far. Thus, the fusion can be applied in rapid, simple,
      and specific diagnosis of Aspergillus contamination in field and stored food/feed
      commodities. 

PMID- 24128349
TI  - Framingham Risk Score underestimates cardiovascular disease risk in severe
      psoriatic patients: implications in cardiovascular risk factors management and
      primary prevention of cardiovascular disease.
AB  - Severe psoriasis has been associated with increase cardiovascular mortality, due
      to a higher prevalence of traditional cardiovascular risk factors and premature
      atherosclerosis, as a consequence of its systemic inflammation. Recently, it has
      been estimated that severe psoriasis may confer an increased 6.2% on long-term
      risk of cardiovascular disease based on Framingham Risk Score, which can have
      practical implications in the treatment of cardiovascular risk factors and
      primary prevention of cardiovascular disease, as treatment guidelines account for
      the risk of cardiovascular disease in treatment goals. The aim of this study was
      to analyze the influence of the attributable risk of severe psoriasis on long
      term risk of cardiovascular disease and its implication on the correct treatment
      of cardiovascular risk factors and primary prevention of cardiovascular disease
      on a real-world cohort of patients. One hundred severe psoriasis patients without
      psoriatic arthritis or previous cardiovascular disease were evaluated and it was
      found that more than half of the patients were reclassified to a higher
      cardiovascular risk category with important clinical implications on the correct
      management of their cardiovascular risk factors and primary prevention of
      cardiovascular disease, as a considerable proportion of patients with
      hypertension, hypercholesterolemia and coronary heart disease equivalent risk
      were not being correctly managed. 

PMID- 24128350
TI  - Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty
      years of research and new directions.
AB  - The advent of the selective cholinergic toxin, 192 IgG-saporin, dramatically
      shaped subsequent research on the role of the basal forebrain in learning and
      memory. In particular, several articles (including the authors' 1995 Behavioral
      Neuroscience paper; M. G. Baxter, D. J. Bucci, L. K., Gorman, R. G. Wiley, & M.
      Gallagher, 1995) revealed that selective removal of basal forebrain cholinergic
      neurons had surprisingly little effect on spatial learning and memory. Here, as
      part of the series commemorating the 30th anniversary of Behavioral Neuroscience,
      we describe how our earlier findings prompted a reconsideration of the
      cholinergic contribution to cognitive function and also led to several new
      research directions, including renewed interest in basal forebrain GABA-ergic
      neurons and cholinergic contributions to neurocognitive development. The authors
      also describe how the successful use of 192 IgG-saporin led to the development
      and popularity of a wide range of selective new neurotoxic agents. Finally, they
      consider the utility of the permanent lesion approach in the wake of new
      transgenic and optogenetic methods.

PMID- 24128351
TI  - Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on
      learning and memory in rats.
AB  - Male Long-Evans rats were given injections of either 192 IgG-saporin, an
      apparently selective toxin for basal forebrain cholinergic neurons (LES), or
      vehicle (CON) into either the medial septum and vertical limb of the diagonal
      band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and
      substantia innominata (nBM/SI). Place discrimination in the Morris water maze
      assessed spatial learning, and a trial-unique matching-to-place task in the water
      maze assessed memory for place information over varying delays. MS/VDB-LES and
      nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the
      place discrimination, but were mildly impaired relative to CON rats in
      performance of the memory task even at the shortest delay, suggesting a
      nonmnemonic deficit. These results contrast with effects of less selective
      lesions, which have been taken to support a role for basal forebrain cholinergic
      neurons in learning and memory.

PMID- 24128352
TI  - Early environments, glucocorticoid receptors, and behavioral epigenetics.
AB  - In 1985, a brief report published in Behavioral Neuroscience established the link
      between neonatal handling and concentrations of hippocampal glucocorticoid
      receptors (GR) in the adult rat, suggesting a neurobiological basis for the
      attenuated stress reactivity observed in handled versus nonhandled offspring. To
      celebrate the 30th anniversary of Behavioral Neuroscience, this article explores
      the research that preceded and followed from this brief but significant
      publication. Changes in hippocampal GR induced by handling were determined to be
      the outcome of a cascade of cellular and molecular events involving thyroid
      hormones, serotonin turnover, and transcription factor binding to the Nr3c1 gene,
      leading to increased GR mRNA and protein. Though many hypotheses were proposed
      for the "handling effect," the role of handling-induced changes in maternal care,
      particularly pup licking/grooming (LG), generated a productive scientific
      framework for understanding the handling phenomenon. Indeed, LG has since been
      demonstrated to alter GR levels through the signaling pathways described for
      handling. Moreover, epigenetic mechanisms have been discovered to play a critical
      role in the effects of early life experience and particularly in the regulation
      of Nr3c1. Overall, the research avenues that have evolved from the initial
      finding of handling-induced changes in GR have broad applications to our
      understanding of plasticity, resilience, and the transmission of traits across
      generations.

PMID- 24128353
TI  - Early postnatal handling alters glucocorticoid receptor concentrations in
      selected brain regions.
AB  - Norway rat pups were either handled (H) or undisturbed (nonhandled, NH) in the
      period between birth and weaning on Day 21. Following weaning, half of the
      animals in each group were housed socially (Soc), and half were housed in
      isolation (Isol). At 120-150 days of age, all animals were sacrificed, and the
      following regions were dissected and frozen at -70  degrees C until the time of
      assay: frontal cortex, hippocampus, hypothalamus, amygdala, septum, and
      pituitary. [3H]Dexamethasone (3H Dex) binding in each region was examined by an
      in vitro, cytosol, receptor assay. 3H Dex binding was significantly higher in the
      hippocampus of both H-Soc and H-Isol than in NH groups. In the frontal cortex, 3H
      Dex binding was higher in the H-Soc animals than in the H-Isol and NH-Isol
      animals. There were no significant handling or housing effects found in the
      amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling
      appears to influence the development of the glucocorticoid receptor system in the
      hippocampus and frontal cortex. These results are discussed as providing a
      possible mechanism for some of the previously reported effects of early handling
      on the development of the pituitary-adrenal response to stress.

PMID- 24128355
TI  - Hippocampus, time, and memory.
AB  - Five experiments were conducted to determine the effects of hippocampal damage on
      timing and the memory for temporal events. In Experiments 1-3, rats were trained
      to discriminate between auditory signals that differed in both duration (2 or 8
      s) and rate (2 or 16 cycles/s). Half of the rats were trained to discriminate
      duration, and half were trained to discriminate rate. After rats acquired the
      relevant discrimination, signals with intermediate durations and rates were
      presented to obtain psychophysical functions that related signal duration and/or
      rate to response choice. Rats then received either lesions of the fimbria-fornix
      or control operations. Postoperatively, the accuracy of duration and rate
      discriminations as measured by the difference limen (DL) was unaffected by the
      lesion, but the point of subjective equality (PSE) was shifted to a shorter
      duration and a slower rate by the lesion in Experiment 1. Both rats with lesions
      and rats with control operations showed cross-modal transfer of duration and rate
      from the auditory signals used in training to visual signals used in testing in
      Experiment 2. A 5-s delay was imposed between the end of a signal and the
      opportunity to respond in Experiment 3. The delay served as a retention interval
      for the rats trained in the rate discrimination, and the rats with fimbria-fornix
      lesions were selectively impaired by the addition of the delay as measured by an
      increase in the DL. The delay did not serve as a retention interval for rats
      trained in the duration discrimination because they were able to continue timing
      through the delay. A peak procedure was employed in Experiment 4. The maximum
      response rate of control rats was approximately at the time of scheduled
      reinforcement (20 s), but the maximum response rate of rats with fimbria-fornix
      lesions was reliably earlier than the time of scheduled reinforcement. When a 5-s
      gap was imposed in the signal, control rats summed the signal durations before
      and after the gap, whereas rats with fimbria-fornix lesions showed no retention
      of the signal duration prior to the gap. Experiment 5 continued the testing of
      the rats used in Experiments 1-4 and showed that rats with lesions had an
      impairment in a test of spatial working memory in an eight-arm radial maze. Taken
      together, these results demonstrate that a fimbria-fornix lesion interferes with
      temporal and spatial working memory, reduces the remembered time of reinforcement
      stored in reference memory, and has no effect on the animal's sensitivity to
      stimulus duration.

PMID- 24128356
TI  - An essential memory trace found.
AB  - I argue here that we have succeeded in localizing an essential memory trace for a
      basic form of associative learning and memory--classical conditioning of discrete
      responses learned with an aversive stimulus--to the anterior interpositus nucleus
      of the cerebellum. We first identified the entire essential circuit, using eyelid
      conditioning as the model system, and used reversible inactivation, during
      training, of critical structures and pathways to localize definitively the
      essential memory trace. In recognition of the 30th anniversary of Behavioral
      Neuroscience, I highlight 1 paper (Tracy, Thompson, Krupa, & Thompson, 1998) that
      was particularly significant for the progress of this research program. In this
      review, I present definitive evidence that the essential memory trace for eyelid
      conditioning is localized to the cerebellum and to no other part of the essential
      circuit, using electrical stimulation of the pontine nuclei-mossy fibers
      projecting to the cerebellum as the conditional stimulus (CS; it proved to be a
      supernormal stimulus resulting in much faster learning than with any peripheral
      CS) and using an electrical stimulus to the output of the cerebellum as a test,
      which did not change. Pontine patterns of projection to the cerebellum were
      confirmed with retrograde labeling techniques.

PMID- 24128354
TI  - Hippocampus, time, and memory--a retrospective analysis.
AB  - In 1984, there was considerable evidence that the hippocampus was important for
      spatial learning and some evidence that it was also involved in duration
      discrimination. The article "Hippocampus, Time, and Memory" (Meck, Church, &
      Olton, 1984), however, was the first to isolate the effects of hippocampal damage
      on specific stages of temporal processing. In this review, to celebrate the 30th
      anniversary of Behavioral Neuroscience, we look back on factors that contributed
      to the long-lasting influence of this article. The major results were that a
      fimbria-fornix lesion (a) interferes with the ability to retain information in
      temporal working memory, and (b) distorts the content of temporal reference
      memory, but (c) did not decrease sensitivity to signal duration. This was the
      first lesion experiment in which the results were interpreted by a well-developed
      theory of behavior (scalar timing theory). It has led to extensive research on
      the role of the hippocampus in temporal processing by many investigators. The
      most important ones are the development of computational models with plausible
      neural mechanisms (such as the striatal beat-frequency model of interval timing),
      the use of multiple behavioral measures of timing, and empirical research on the
      neural mechanisms of timing and temporal memory using ensemble recording of
      neurons in prefrontal-striatal-hippocampal circuits.

PMID- 24128357
TI  - Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during
      classical conditioning of the eyeblink response in the rabbit.
AB  - Electrical stimulation thresholds required to elicit eyeblinks with either
      pontine or cerebellar interpositus stimulation were measured before and after
      classical eyeblink conditioning with paired pontine stimulation (conditioned
      stimulus, CS) and corneal airpuff (unconditioned stimulus, US). Pontine
      stimulation thresholds dropped dramatically after training and returned to
      baseline levels following extinction, whereas interpositus thresholds and input
      output functions remained stable across training sessions. Learning rate,
      magnitude of threshold change, and electrode placements were correlated. Pontine
      projection patterns to the cerebellum were confirmed with retrograde labeling
      techniques. These results add to the body of literature suggesting that the pons
      relays CS information to the cerebellum and provide further evidence of synaptic
      plasticity in the cerebellar network.

PMID- 24128358
TI  - Differential effects of the cannabinoid agonist WIN55,212-2 on delay and trace
      eyeblink conditioning.
AB  - Central cannabinoid-1 receptors (CB1R) play a role in the acquisition of delay
      eyeblink conditioning (EBC) but not trace EBC in humans and animals. However, it
      is not clear why trace conditioning is immune to the effects of cannabinoid
      receptor compounds. The current study examined the effects of variants of delay
      and trace conditioning procedures to elucidate the factors that determine the
      effects of CB1R agonists on EBC. In Experiment 1, rats were administered the
      cannabinoid agonist WIN55,212-2 during delay, long-delay, or trace conditioning.
      Rats were impaired during delay and long-delay, but not trace conditioning; the
      impairment was greater for long-delay than delay conditioning. Trace conditioning
      was further examined in Experiment 2 by manipulating the trace interval and
      keeping constant the conditioned stimulus (conditional stimulus [CS]) duration.
      It was found that when the trace interval was 300 ms or less, WIN55,212-2
      administration impaired the rate of learning. Experiment 3 tested whether the
      trace interval duration or the relative durations of the CS and trace interval
      were critical parameters influencing the effects of WIN55,212-2 on EBC. Rats were
      not impaired with a 100-ms CS, 200-ms trace paradigm but were impaired with a
      1,000-ms CS, 500-ms trace paradigm, indicating that the duration of the trace
      interval does not matter, but the proportion of the interstimulus interval
      occupied by the CS relative to the trace period is critical. Taken together, the
      results indicate that cannabinoid agonists affect cerebellar learning when the CS
      is longer than the trace interval.

PMID- 24128359
TI  - Acute early-life stress results in premature emergence of adult-like fear
      retention and extinction relapse in infant rats.
AB  - Recent studies have shown that chronic early life stress results in precocious
      expression of the adult-like phenotype of fear retention and inhibition. However,
      it is unknown whether the experience of acute early trauma has the same effects
      as exposure to chronic early stress. In the present study, a 24-hr period of
      maternal deprivation on postnatal day (P) 9 was used as an acute early life
      stressor. In infancy (P16-17), maternally deprived and standard-reared rats were
      conditioned to fear a noise paired with shock. In Experiments 1 and 2, fear to
      the noise was then extinguished before rats were tested for context-mediated fear
      renewal or stress-induced fear reinstatement. In Experiments 3a and 3b,
      conditioned rats were tested for fear retention 1, 7, or 14 days after training.
      Whereas standard-reared infants exhibited relapse-resistant extinction and
      infantile amnesia (i.e., behaviors typical of their age), maternally deprived
      infants exhibited the renewal and reinstatement effects (i.e., relapse-prone
      extinction) and showed good retention of fear over the 7- and 14-day intervals
      (i.e., infantile amnesia was reduced). In other words, similar to rats exposed to
      chronic early life stress, rats exposed to acute early stress expressed an adult
      like profile of fear retention and inhibition during infancy. These findings
      suggest that similar mechanisms might be involved in the effects of acute and
      chronic stress on emotional development, and may have implications for our
      understanding and treatment of emotional disorders associated with early
      adversity.

PMID- 24128360
TI  - Environmental rearing effects on impulsivity and reward sensitivity.
AB  - Previous research has indicated that rearing in an enriched environment may
      promote self-control in an impulsive choice task. To further assess the effects
      of rearing environment on impulsivity, 2 experiments examined locomotor activity,
      impulsive action, impulsive choice, and different aspects of reward sensitivity
      and discrimination. In Experiment 1, rats reared in isolated or enriched
      conditions were tested on an impulsive choice procedure with a smaller-sooner
      versus a larger-later reward, revealing that the isolated rats valued the smaller
      sooner reward more than the enriched rats. A subsequent reward challenge was
      presented in which the delay to the 2 rewards was the same but the magnitude
      difference remained. The enriched rats did not choose the larger reward as often
      as the isolated rats, reflecting poorer reward discrimination. Impulsive action
      was assessed using a differential-reinforcement-of-low-rate task, which revealed
      deficits in the enriched rats. In Experiment 2, rats reared in isolated,
      standard, or enriched conditions were tested on reward contrast and reward
      magnitude sensitivity procedures. The rats were presented with 2 levers that
      delivered different magnitudes of food on variable interval 30-s schedules.
      Across all tests, the enriched and social rats displayed more generalized
      responding to the small-reward lever, but a similar response to the large-reward
      lever, compared with the isolated rats. This confirmed the results of Experiment
      1, indicating poorer reward discrimination in the enriched condition compared
      with the isolated condition. The results suggest that enrichment may moderate
      reward generalization/discrimination processes through alterations in incentive
      motivational processes.

PMID- 24128361
TI  - Sexually dimorphic recruitment of dopamine neurons into the stress response
      circuitry.
AB  - Several previous studies in mammalian systems have shown sexually dimorphic
      behaviors, neuroendocrine changes, and alterations in neurotransmitter release in
      response to stress. In addition, men and women are differentially vulnerable to
      stress-related pathologies, which have led to the hypothesis that the stress
      response circuitry differs depending on sex. The authors used the genetic
      tractability of Drosophila to manipulate pre- or postsynaptic dopamine signaling
      in transgenic animals, which were assayed for several parameters of locomotion
      and heart rate following exposure to 2 environmental stressors: starvation and
      oxidative stress. Their results show significant differences in the stress
      response for males and females by analyzing heart rate, centering time, and high
      mobility in addition to other locomotor parameters with translational relevance.
      These data demonstrate that both pre- and postsynaptic neurons are differentially
      recruited into the dopaminergic stress response circuitry for males and females.
      The results also show that the response circuits differ depending on the stressor
      and behavioral output. Furthermore, the authors' studies provide a translatable
      Drosophila model for further elucidation of factors involved in the sexually
      dimorphic recruitment of neurons into the stress response circuitry.

PMID- 24128364
TI  - High energy diets prevent the enhancing effects of emotional arousal on memory.
AB  - Over the past five decades, per capita caloric intake has increased by
      approximately 28% in the United States. Excessive intake of calories from fats
      and sugars (high energy diets; HEDs) negatively impacts hippocampal-dependent
      memory. These deleterious effects of HEDs on hippocampal function involve HED
      induced decreases in neuronal growth factors, neurogenesis, and synaptic
      plasticity. Given that HEDs also alter responses to emotional arousal, the
      present experiment determined whether the effects of HEDs on memory depend on the
      emotional arousal produced by the memory task during encoding. Rats were fed a
      high fat/sugar cafeteria-style diet for 4 weeks and then tested in a low or high
      emotional arousal version of a spatial object place recognition task. The results
      demonstrated that the HED prevented the memory-enhancing effects of emotional
      arousal. Thus, altered responses to emotional arousal likely contribute to HED
      induced memory impairments, particularly in stressful memory tasks such as the
      spatial water maze.

PMID- 24128363
TI  - Fischer rats are more sensitive than Lewis rats to the suppressive effects of
      morphine and the aversive kappa-opioid agonist spiradoline.
AB  - Data have suggested that rats avoid intake of an otherwise palatable saccharin
      cue when paired with a drug of abuse, at least, in part, because the value of the
      taste cue pales in anticipation of the availability of the highly rewarding drug.
      Earlier support for this hypothesis was provided by the finding that, relative to
      the less sensitive Fischer rats, Lewis rats exhibit greater avoidance of a
      saccharin cue when paired with a rewarding sucrose or cocaine unconditioned
      stimulus (US), but not when paired with the aversive agent, lithium chloride.
      More recent data, however, have shown that Fischer rats actually exhibit greater,
      not less, avoidance of the same saccharin cue when morphine serves as the US.
      Therefore, Experiment 1 evaluated morphine-induced suppression of intake of the
      taste cue in Lewis and Fischer rats when the morphine US was administered
      subcutaneously, rather than intraperitoneally. Experiment 2 examined the effect
      of strain on the suppression of intake of the saccharin cue when paired with
      spiradoline, a selective kappa-opioid receptor agonist. The results confirmed
      that Fischer rats are more responsive to the suppressive effects of morphine than
      Lewis rats, and that Fischer rats also exhibit greater avoidance of the saccharin
      cue when paired with spiradoline, despite the fact that spiradoline is devoid of
      reinforcing properties. Taken together, the data suggest that the facilitated
      morphine-induced suppression observed in Fischer rats, compared with Lewis rats,
      may reflect an increased sensitivity to the aversive, kappa-mediated properties
      of opiates.

PMID- 24128365
TI  - Relationship between oxytocin receptor genotype and recognition of facial
      emotion.
AB  - The ability to understand thoughts and feelings of another person is an important
      prerequisite for successful social interaction. One part of this ability is the
      recognition of emotions in the face of the counterpart. Knowledge on genetic
      contributions to emotion recognition is still scarce. In the present study, 105
      healthy participants were experimentally tested for their ability to recognize
      complex emotions in faces. As prior studies outlined the importance of the
      oxytocin system for emotion recognition, the functional rs2268498 polymorphism on
      the OXTR-gene was investigated. Although there were no differences in reaction
      times between genotype groups, carriers of the T-allele exhibited more accurate
      recognition skills than subjects carrying the CC-genotype. There was no influence
      of gender or age. Results support recent findings, demonstrating the importance
      of the oxytocin system for affect processing and related social behavior.

PMID- 24128366
TI  - Are object affordances fully automatic? A case of covert attention.
AB  - Inspired in part by Gibson's (1979) ecological approach to perception, current
      neurocognitive theories of action suggest that the simple viewing of an object
      can automatically elicit motor programs for specific acts. However, the degree to
      which such affordances should be considered truly automatic is unknown. Here we
      explored the generation of motor plans afforded by pairs of cue objects that were
      viewed peripherally under different attentional states. Participants focused
      centrally while attending to just one of two peripheral cue objects that together
      had a strong significance for pinching, grasping, or both. They were instructed
      to ignore the objects and instead give power or precision grip responses to
      subsequent changes in background color. The data showed a significant interaction
      between type of response and type of object, indicating that object affordances
      are perceived even in nonfoveal vision. Critically, the generation of affordances
      was modulated by the locus of attention: Motor preparation was biased toward the
      attended object when two different categories of object appeared in the same
      trial, but the generation of affordances was also influenced by unattended
      stimuli. This finding demonstrates that object-action priming is not completely
      automatic, instead being constrained by processes of perceptual selection.

PMID- 24128367
TI  - Sleep quality in healthy older people: relationship with 1H magnetic resonance
      spectroscopy markers of glial and neuronal integrity.
AB  - The hippocampus and thalamus assume a significant role in the overnight
      consolidation of memories, a process that is negatively impacted by sleep
      disruption. Emerging evidence suggests that disturbances of sleep in older people
      may co-occur with underlying neurobiological changes. This study sought to assess
      glial and neuronal integrity in these regions in relation to subjective sleep
      disturbance in a healthy older sample. Forty-three healthy older people (mean age
      = 70, SD = 5.0) were assessed clinically and medically and screened for cognitive
      and depressive symptoms, as well as sleep disturbance. Single voxel hippocampal
      and thalamus metabolite ratios of N-acetyl aspartate (NAA) and myo-inositol (mI)
      with total creatine (Cr + PCr) were measured using magnetic resonance
      spectroscopy at 3-Tesla. Higher hippocampal mI/Cr + PCr ratios were significantly
      correlated with poorer self-reported sleep quality (r = .42, p < .01) and less
      sleep efficiency (r = -0.42, p < .01) as recorded by the Pittsburgh Sleep Quality
      Index (Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). No other significant
      correlations were observed within the hippocampus or within the thalamus. These
      results indicate that in healthy older people, subjective sleep disturbance may
      be associated with glial alterations in the hippocampus. Future research is now
      needed to examine these associations with respect to objective sleep measures and
      overnight memory consolidation.

PMID- 24128369
TI  - Measurement of left and right atrial volume in patients undergoing ablation for
      atrial arrhythmias: comparison of a manual versus semiautomatic algorithm of real
      time 3D echocardiography.
AB  - AIMS: Real time full-volume 3D echocardiography (3DE) allows rapid and
      noninvasive measurement of left (LA) and right atrial (RA) volume without
      geometric assumptions. Different algorithms from different commercial providers
      are available. Older software requires manual tracing of endocardial contours.
      Recently, software with semiautomatic endocardial contour-finding algorithms has
      become available, which considerably speeds up the procedure. Our aim was to
      compare, in the same dataset, both LA and RA volumes determined by an algorithm
      involving manual tracing to the corresponding volumes obtained by an algorithm
      with semiautomatic contour detection. METHODS: Maximal atrial volumes were
      measured in 88 patients using a multiplane interpolation method algorithm based
      on manual planimetry of 8 slices. These volumes were compared with volumes
      determined by the QLAB 8.1 software using semiautomatic border detection.
      RESULTS: Linear regression showed excellent correlation between volumes
      determined by manual and by semiautomatic software for both LA and RA (r(2) =
      0.90 and 0.89, respectively, P < 0.001). Bland-Altman analysis of manual versus
      semiautomatic volume determination showed narrow 95% limits of agreement (-15.9
      to +12.0 mL for LA volume and -13.9 to +12.2 mL for RA volume) with a minimal
      bias of -1.9 +/- 7.0 mL and -0.8 +/- 6.5 mL, respectively, by the semiautomatic
      method. CONCLUSION: The semiautomatic border detection method shows excellent
      correlation for maximal LA and RA volume determination compared to the more time
      consuming, multiplane interpolation method, with only slight underestimation. The
      results indicate that values of LA and RA volumes obtained by either algorithm
      can be compared, for example, during follow-up examinations.

PMID- 24128370
TI  - Agrobacterium T-DNA-encoded protein Atu6002 interferes with the host auxin
      response.
AB  - Several genes in the Agrobacterium tumefaciens transferred (T)-DNA encode
      proteins that are involved in developmental alterations, leading to the formation
      of tumours in infected plants. We investigated the role of the protein encoded by
      the Atu6002 gene, the function of which is completely unknown. Atu6002 expression
      occurs in Agrobacterium-induced tumours, and is also activated on activation of
      plant cell division by growth hormones. Within the expressing plant cells, the
      Atu6002 protein is targeted to the plasma membrane. Interestingly, constitutive
      ectopic expression of Atu6002 in transgenic tobacco plants leads to a severe
      developmental phenotype characterized by stunted growth, shorter internodes,
      lanceolate leaves, increased branching and modified flower morphology. These
      Atu6002-expressing plants also display impaired response to auxin. However, auxin
      cellular uptake and polar transport are not significantly inhibited in these
      plants, suggesting that Atu6002 interferes with auxin perception or signalling
      pathways. 

PMID- 24128371
TI  - On the size and structure of helium snowballs formed around charged atoms and
      clusters of noble gases.
AB  - Helium nanodroplets doped with argon, krypton, or xenon are ionized by electrons
      and analyzed in a mass spectrometer. HenNgx(+) ions containing up to seven noble
      gas (Ng) atoms and dozens of helium atoms are identified; the high resolution of
      the mass spectrometer combined with advanced data analysis make it possible to
      unscramble contributions from isotopologues that have the same nominal mass but
      different numbers of helium or Ng atoms, such as the magic He20(84)Kr2(+) and the
      isobaric, nonmagic He41(84)Kr(+). Anomalies in these ion abundances reveal
      particularly stable ions; several intriguing patterns emerge. Perhaps most
      astounding are the results for HenAr(+), which show evidence for three distinct,
      solid-like solvation shells containing 12, 20, and 12 helium atoms. This
      observation runs counter to the common notion that only the first solvation shell
      is solid-like but agrees with calculations by Galli et al. for HenNa(+) [J. Phys.
      Chem. A 2011, 115, 7300] that reveal three shells of icosahedral symmetry.
      HenArx(+) (2 <= x <= 7) ions appear to be especially stable if they contain a
      total of n + x = 19 atoms. A sequence of anomalies in the abundance distribution
      of HenKrx(+) suggests that rings of six helium atoms are inserted into the
      solvation shell each time a krypton atom is added to the ionic core, from Kr(+)
      to Kr3(+). Previously reported strong anomalies at He12Kr2(+) and He12Kr3(+) [Kim
      , J. H.; et al. J. Chem. Phys. 2006, 124, 214301] are attributed to a
      contamination. Only minor local anomalies appear in the distributions of
      HenXex(+) (x <= 3). The distributions of HenKr(+) and HenXe(+) show strikingly
      similar, broad features that are absent from the distribution of HenAr(+);
      differences are tentatively ascribed to the very different fragmentation dynamics
      of these ions.

PMID- 24128372
TI  - MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain
      of ZNF274 as a feedback mechanism.
AB  - The ACE2 (angiotensin-converting enzyme 2)/Ang-(1-7) [angiotensin-(1-7)]/MAS axis
      of the RAS (renin-angiotensin system) has emerged as a pathway of interest in
      treating both cardiovascular disorders and cancer. The MAS protein is known to
      bind to and be activated by Ang-(1-7); however, the mechanisms of this activation
      are just starting to be understood. Although there are strong biochemical data
      regarding the regulation and activation of the AT1R (angiotensin II type 1
      receptor) and the AT2R (angiotensin II type 2 receptor), with models of how AngII
      (angiotensin II) binds each receptor, fewer studies have characterized MAS. In
      the present study, we characterize the MAS promoter and provide a potential
      feedback mechanism that could compensate for MAS degradation following activation
      by Ang-(1-7). Analysis of ENCODE data for the MAS promoter revealed potential
      epigenetic control by KRAB (Kruppel-associated box)/KAP-1 (KRAB-associated
      protein-1). A proximal promoter construct for the MAS gene was repressed by the
      SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2,
      SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. The KRAB
      KAP-1 complex can be tyrosine-nitrated, causing the dissociation of the KAP-1
      protein and thus a potential loss of epigenetic control. Activation of MAS can
      lead to an increase in nitric oxide, suggesting a feedback mechanism for MAS on
      its own promoter. The results of the present study provide a more complete view
      of MAS regulation and, for the first time, suggest biochemical outcomes for
      nitration of the KRAB domain. 

PMID- 24128373
TI  - Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in
      dogs with myxomatous mitral valve disease and congestive heart failure.
AB  - BACKGROUND: Pimobendan and benazepril are frequently used with diuretics to treat
      dogs in congestive heart failure (CHF) caused by myxomatous mitral valve disease
      (MMVD). AIM: To compare the short-term effects of pimobendan versus benazepril on
      pump function, heart size, and neuroendocrine profile in dogs with CHF caused by
      MMVD. ANIMALS: Sixteen client-owned dogs. MATERIAL AND METHODS: Seven-day
      prospective single-blinded study of dogs stabilized on furosemide monotherapy,
      randomized to pimobendan (0.4-0.6 mg/kg/day) or benazepril (0.25-1.0 mg/kg/day).
      Dogs had first-pass radionuclide angiocardiography, and heart size was measured
      by radiography and echocardiography. Circulating neuroendocrine hormones were
      measured. RESULTS: Baseline variables did not differ between treatment groups.
      Greater decreases in the pimobendan than in the benazepril group were found for
      heart rate (P = .001), heart rate-normalized pulmonary transit time (P = .02),
      left atrial size (P = .03), and systolic and diastolic left ventricular diameters
      (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02,
      respectively), whereas ejection fraction increased more (P = .02) in the
      pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial
      natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups,
      plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type
      (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P
      = .02) and plasma vasopressin (P = .01) decreased in the benazepril group.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan improves short-term cardiac
      function more than benazepril in dogs with CHF caused by MMVD. Pimobendan
      treatment enables the heart to work at smaller end-systolic and diastolic
      dimensions while maintaining adequate forward stroke volume. Some of the
      treatment responses found in neuroendocrine profile might have therapeutic
      relevance.

PMID- 24128375
TI  - Proteome profiling of the dimorphic fungus Penicillium marneffei extracellular
      proteins and identification of glyceraldehyde-3-phosphate dehydrogenase as an
      important adhesion factor for conidial attachment.
AB  - Despite being the most important thermal dimorphic fungus causing systemic
      mycosis in Southeast Asia, the pathogenic mechanisms of Penicillium marneffei
      remain largely unknown. By comparing the extracellular proteomes of P. marneffei
      in mycelial and yeast phases, we identified 12 differentially expressed proteins
      among which glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and heat shock
      protein 60 (HSP60) were found to be upregulated in mycelial and yeast phases
      respectively. Based on previous findings in other pathogens, we hypothesized that
      these two extracellular proteins may be involved in adherence during P. marneffei
      host interaction. Using inhibition assays with recombinant GAPDH (rGAPDH)
      proteins and anti-rGAPDH sera, we demonstrated that adhesion of P. marneffei
      conidia to fibronectin and laminin was inhibited by rGAPDH or rabbit anti-rGAPDH
      serum in a dose-dependent manner. Similarly, a dose-dependent inhibition of
      conidial adherence to A549 pneumocytes by rGAPDH or rabbit anti-rGAPDH serum was
      observed, suggesting that P. marneffei GAPDH can mediate binding of conidia to
      human extracellular matrix proteins and pneumocytes. However, HSP60 did not
      exhibit similar inhibition on conidia adherence, and neither GAPDH norHSP60
      exhibited inhibition on adherence to J774 or THP-1 macrophage cell lines. This
      report demonstrates GAPDH as an adherence factor in P. marneffei by mediating
      conidia adherence to host bronchoalveolar epithelium during the early
      establishment phase of infection. 

PMID- 24128376
TI  - Medical malpractice claims in relation to colorectal malignancy in the national
      health service.

PMID- 24128374
TI  - The impact of patients' gender, race, and age on health care professionals' pain
      management decisions: an online survey using virtual human technology.
AB  - BACKGROUND: Previous literature indicates that biases exist in pain ratings.
      Healthcare professionals have been found to use patient demographic cues such as
      sex, race, and age when making decisions about pain treatment. However, there has
      been little research comparing healthcare professionals' (i.e., physicians and
      nurses) pain decision policies based on patient demographic cues. METHODS: The
      current study used virtual human technology to examine the impact of patients'
      sex, race, and age on healthcare professionals' pain ratings. One hundred and
      ninety-three healthcare professionals (nurses and physicians) participated in
      this online study. RESULTS: Healthcare professionals assessed virtual human
      patients who were male and African American to be experiencing greater pain
      intensity and were more willing to administer opioid analgesics to them than to
      their demographic counterparts. Similarly, nurses were more willing to administer
      opioids make treatment decisions than physicians. There was also a significant
      virtual human-sex by healthcare professional interaction for pain assessment and
      treatment decisions. The sex difference (male>female) was greater for nurses than
      physicians. CONCLUSIONS: Results replicated findings of previous studies using
      virtual human patients to assess the effect of sex, race, and age in pain
      decision-making. In addition, healthcare professionals' pain ratings differed
      depending on healthcare profession. Nurses were more likely to rate pain higher
      and be more willing to administer opioid analgesics than were physicians.
      Healthcare professionals rated male and African American virtual human patients
      as having higher pain in most pain assessment and treatment domains compared to
      their demographic counterparts. Similarly the virtual human-sex difference
      ratings were more pronounced for nurses than physicians. Given the large number
      of patients seen throughout the healthcare professionals' careers, these pain
      practice biases have important public health implications. This study suggests
      attention to the influence of patient demographic cues in pain management
      education is needed.

PMID- 24128377
TI  - Widespread phenotypic and genetic divergence along altitudinal gradients in
      animals.
AB  - Altitudinal gradients offer valuable study systems to investigate how adaptive
      genetic diversity is distributed within and between natural populations and which
      factors promote or prevent adaptive differentiation. The environmental clines
      along altitudinal gradients tend to be steep relative to the dispersal distance
      of many organisms, providing an opportunity to study the joint effects of
      divergent natural selection and gene flow. Temperature is one variable showing
      consistent altitudinal changes, and altitudinal gradients can therefore provide
      spatial surrogates for some of the changes anticipated under climate change.
      Here, we investigate the extent and patterns of adaptive divergence in animal
      populations along altitudinal gradients by surveying the literature for (i)
      studies on phenotypic variation assessed under common garden or reciprocal
      transplant designs and (ii) studies looking for signatures of divergent selection
      at the molecular level. Phenotypic data show that significant between-population
      differences are common and taxonomically widespread, involving traits such as
      mass, wing size, tolerance to thermal extremes and melanization. Several lines of
      evidence suggest that some of the observed differences are adaptively relevant,
      but rigorous tests of local adaptation or the link between specific phenotypes
      and fitness are sorely lacking. Evidence for a role of altitudinal adaptation
      also exists for a number of candidate genes, most prominently haemoglobin, and
      for anonymous molecular markers. Novel genomic approaches may provide valuable
      tools for studying adaptive diversity, also in species that are not amenable to
      experimentation. 

PMID- 24128378
TI  - Analytical approaches for the characterization and identification of olive (Olea
      europaea) oil proteins.
AB  - Proteins in olive oil have been scarcely investigated probably due to the
      difficulty of working with such a lipidic matrix and the dramatically low
      abundance of proteins in this biological material. Additionally, this scarce
      information has generated contradictory results, thus requiring further
      investigations. This work treats this subject from a comprehensive point of view
      and proposes the use of different analytical approaches to delve into the
      characterization and identification of proteins in olive oil. Different
      extraction methodologies, including capture via combinational hexapeptide ligand
      libraries (CPLLs), were tried. A sequence of methodologies, starting with off-gel
      isoelectric focusing (IEF) followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) or high-performance liquid chromatography (HPLC) using
      an ultraperformance liquid chromatography (UPLC) column, was applied to profile
      proteins from olive seed, pulp, and oil. Besides this, and for the first time, a
      tentative identification of oil proteins by mass spectrometry has been attempted.

PMID- 24128379
TI  - Integration of health services improves multiple healthcare outcomes among HIV
      infected people who inject drugs in Ukraine.
AB  - BACKGROUND: People who inject drugs (PWID) experience poor outcomes and fuel HIV
      epidemics in middle-income countries in Eastern Europe and Central Asia. We
      assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which
      despite international recommendations, is neither widely available nor
      empirically examined. METHODS: A 2010 cross-sectional study randomly sampled 296
      HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in
      Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO)
      settings are available. ICL settings provide onsite HIV, addiction, and
      tuberculosis services, NCLs only treat addiction, and HROs provide counseling,
      needles/syringes, and referrals, but no opioid substitution therapy (OST). The
      primary outcome was receipt of quality healthcare, measured using a quality
      healthcare indicator (QHI) composite score representing percentage of eight
      guidelines-based recommended indicators met for HIV, addiction and tuberculosis
      treatment. The secondary outcomes were individual QHIs and health-related quality
      of-life (HRQoL). RESULTS: On average, ICL-participants had significantly higher
      QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8%
      versus 37.0%, p<0.001) even after controlling for potential confounders. Compared
      to NCL-participants, ICL-participants were significantly more likely to receive
      antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4 <= 200
      (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus
      41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001).
      Subjects receiving OST had significantly higher HRQoL than those not receiving it
      (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL
      participants. CONCLUSIONS: These findings suggest that OST alone improves quality
      of-life, while receiving care in integrated settings collectively and
      individually improves healthcare quality indicators for PWID.

PMID- 24128380
TI  - Estimation of usual occasion-based individual drinking patterns using diary
      survey data.
AB  - BACKGROUND: In order to successfully address excessive alcohol consumption it is
      essential to have a means of measuring the drinking patterns of a nation. Owing
      to the multi-dimensional nature of drinking patterns, usual survey methods have
      their limitations. The aim of this study was to make use of extremely detailed
      diary survey data to demonstrate a method of combining different survey measures
      of drinking in order to reduce these limitations. METHODS: Data for 1724
      respondents of the 2000/01 National Diet and Nutrition Survey was used to obtain
      a drinking occasion dataset, by plotting the respondent's blood alcohol content
      over time. Drinking frequency, level and variation measures were chosen to
      characterise drinking behaviour and usual behaviour was estimated via statistical
      methods. RESULTS: Complex patterns in drinking behaviour were observed amongst
      population subgroups using the chosen consumption measures. The predicted
      drinking distribution combines diary data equivalent coverage with a more
      accurate proportion of non-drinkers. CONCLUSIONS: This statistical analysis
      provides a means of obtaining average consumption measures from diary data and
      thus reducing the main limitation of this type of data for many applications. We
      hope that this will facilitate the use of such data in a wide range of
      applications such as risk modelling, especially for acute harms, and burden of
      disease studies.

PMID- 24128381
TI  - Achieving smoking abstinence is associated with decreased cocaine use in cocaine
      dependent patients receiving smoking-cessation treatment.
AB  - BACKGROUND: Past research suggests that a significant relationship exists between
      cigarette smoking and illicit-stimulant abuse. The present study evaluated the
      association between achieving smoking abstinence in response to smoking-cessation
      treatment (SCT) and illicit-stimulant abstinence in cocaine- and/or
      methamphetamine-dependent participants. METHODS: Secondary analysis of a
      randomized, 10-week trial conducted at 12 substance use disorder (SUD) treatment
      programs. Two hundred and sixty seven adults, meeting DSM-IV-TR criteria for
      cocaine and/or methamphetamine-dependence and interested in quitting smoking were
      randomized to SUD treatment as usual plus SCT consisting of weekly individual
      smoking cessation counseling, extended-release (XL) bupropion (300 mg/day),
      nicotine inhaler, and contingency management for smoking abstinence. Illicit
      stimulant-abstinence was measured by self-report and urine drug screens. Smoking
      abstinence was assessed via self-report and carbon monoxide levels. RESULTS: A
      significant effect was found for the cocaine-dependent subsample (N=147) in which
      participants who stopped smoking were abstinent for illicit stimulants an average
      of 78.2% of the post-smoking-quit weeks (weeks 4-10) relative to 63.6% in
      participants who continued smoking (X(2)(1)=8.55, p<.01, d=0.36). No significant
      effects were found for the sample as a whole (N=249) or for the methamphetamine
      dependent subsample (N=102). CONCLUSIONS: The present results suggest that
      cocaine-dependent patients achieving smoking abstinence in response to SCT might
      evidence not only improved smoking outcomes but improved cocaine-use outcomes as
      well. Future research to replicate this finding appears warranted.

PMID- 24128382
TI  - Fast mapping of the cobalt-valence state in Ba0.5Sr0.5Co0.8Fe0.2O3-d by electron
      energy loss spectroscopy.
AB  - A fast method for determination of the Co-valence state by electron energy loss
      spectroscopy in a transmission electron microscope is presented. We suggest the
      distance between the Co-L3 and Co-L2 white-lines as a reliable property for the
      determination of Co-valence states between 2+ and 3+. The determination of the Co
      L2,3 white-line distance can be automated and is therefore well suited for the
      evaluation of large data sets that are collected for line scans and mappings.
      Data with a low signal-to-noise due to short acquisition times can be processed
      by applying principal component analysis. The new technique was applied to study
      the Co-valence state of Ba0.5Sr0.5Co0.8Fe0.2O3-d (BSCF), which is hampered by the
      superposition of the Ba-M4,5 white-lines on the Co-L2,3 white-lines. The Co
      valence state of the cubic BSCF phase was determined to be 2.2+ (+/-0.2) after
      annealing for 100 h at 650 degrees C, compared to an increased valence state of
      2.8+ (+/-0.2) for the hexagonal phase. These results support models that
      correlate the instability of the cubic BSCF phase with an increased Co-valence
      state at temperatures below 840 degrees C. 

PMID- 24128383
TI  - Directed formation of a ferrocenyl-decorated organotin sulfide complex and its
      controlled degradation.
AB  - Attachment of ferrocenyl (Fc) units to an organo-functionalized precursor yielded
      the Fc-decorated complex [(R(Fc)Sn)4Sn6S10] [1; R(Fc) = CMe2CH2C(Me)?N
      N?C(Me)Fc], which shows different ligand dynamics in solution than in the solid
      state, as confirmed by NMR spectroscopy and by cyclic and differential pulse
      voltammetry. The addition of different amounts of hydrochloric acid to a solution
      of 1 produced the derivatives [(R(Fc)SnCl2)2S] (2) and [R(Fc)SnCl3.HCl] (3), the
      latter of which acts as a precursor to the formation/recovery of 2 or 1,
      respectively. 

PMID- 24128384
TI  - Visible-light-induced water splitting based on two-step photoexcitation between
      dye-sensitized layered niobate and tungsten oxide photocatalysts in the presence
      of a triiodide/iodide shuttle redox mediator.
AB  - Water splitting into H2 and O2 under visible light was achieved using simple
      organic dyes such as coumarin and carbazole as photosensitizers on an n-type
      semiconductor for H2 evolution, a tungsten(VI) oxide (WO3) photocatalyst for O2
      evolution, and a triiodide/iodide (I3(-)/I(-)) redox couple as a shuttle electron
      mediator between them. The results on electrochemical measurements revealed that
      the oxidized states of the dye molecules having an oligothiophene moiety (two or
      more thiophene rings) in their structures are relatively stable even in water and
      possess sufficiently long lifetimes to exhibit reversible oxidation-reduction
      cycles, while the carbazole system required more thiophene rings than the
      coumarin one to be substantially stabilized. The long lifetimes of the oxidized
      states enabled these dye molecules to be regenerated to the original states by
      accepting an electron from the I(-) electron donor even in an aqueous solution,
      achieving sustained H2 and I3(-) production from an aqueous KI solution under
      visible light irradiation when they were combined with an appropriate n-type
      semiconductor, ion-exchangeable layered niobate H4Nb6O17. The use of H4Nb6O17
      loaded with Pt cocatalyst inside the interlayer allowed the water reduction to
      proceed preferentially with a steady rate even in the presence of a considerable
      amount of I3(-) in the solution, due to the inhibited access of I3(-) to the
      reduction site, Pt particles inside, by the electrostatic repulsion between the
      I3(-) anions and the negatively charged (Nb6O17)(4-) layers. It was also revealed
      that the WO3 particles coloaded with Pt and IrO2 catalysts exhibited higher rates
      of O2 evolution than the WO3 particles loaded only with Pt in aqueous solutions
      containing a considerable amount of I(-), which competitively consumes the holes
      and lowers the rate of O2 evolution on WO3 photocatalysts. The enhanced O2
      evolution is certainly due to the improved selectivity of holes toward water
      oxidation on IrO2 cocatalyst, instead of undesirable oxidation of I(-).
      Simultaneous evolution of H2 and O2 under visible light was then achieved by
      combining the Pt/H4Nb6O17 semiconductor sensitized with the dye molecules having
      an oligothiophene moiety, which can stably generate H2 and I3(-) from an aqueous
      KI solution, with the IrO2-Pt-loaded WO3 photocatalyst that can reduce the I3(-)
      back to I(-) and oxidize water to O2. 

PMID- 24128385
TI  - Long term results of Epi-LASIK and LASEK for myopia.
AB  - PURPOSE: To evaluate the long term clinical and confocal results of mechanical
      (Epi-LASIK) versus alcohol-assisted laser epithelial keratomileusis (LASEK) for
      correction of myopia. SETTING: Gazi University Medical School, Department of
      Ophthalmology, Ankara, Turkey. DESIGN: Retrospective study. METHODS: Twenty-two
      eyes treated with LASEK and twenty eyes treated with Epi-LASIK were evaluated
      with a mean follow-up duration of 45 months. Mechanical separation of the
      epithelium was performed with Lasitome epithelial separator, and alcohol-assisted
      separation with 25s application of 18% alcohol. Laser ablation was performed with
      the ESIRIS laser. All patients were examined daily until epithelial closure; at
      1, 3, 6, and 12 months; and every year subsequently. Main outcome measures were
      uncorrected visual acuity (UCVA), manifest refraction, haze, and gray scale value
      in confocal microscopy, efficacy and safety indexes. RESULTS: Preoperative myopic
      spherical equivalent refraction was -4.65 +/- 1.74 D in the LASEK and -3.87 +/-
      1.30 D in the Epi-LASIK-treated eyes (p=0.36). Of both LASEK and Epi-LASIK
      treated eyes, 95% achieved 20/25 or better final UCVA. The grade of haze and mean
      gray scale value in confocal microscopy were similar in LASEK and Epi-LASIK
      treated eyes at all postoperative periods. The efficacy index was 0.94 in LASEK
      group and 0.96 in Epi-LASIK group (p=0.44). The safety index was 1.01 in LASEK
      group and 1.02 in Epi-LASIK group (p=0.42). CONCLUSIONS: Both LASEK and Epi-LASIK
      offer safe and effective correction of myopia in the long term.

PMID- 24128386
TI  - GPs opinions and perceptions of chiropractic in Sweden and Norway: a descriptive
      survey.
AB  - BACKGROUND: In Sweden, chiropractic is not included in mainstream health care. In
      Norway chiropractic is a recognized health care profession. The aim of this study
      was to explore the perceptions of chiropractic among Swedish and Norwegian
      General Practitioners (GPs). METHODS: Eight hundred surveys in each country were
      distributed randomly by post to Swedish and Norwegian GPs offices. The survey
      contained two main sections: Experiences and opinions about chiropractic and
      referral patterns. The data were then described and compared between the
      countries. RESULTS: In Sweden the response rate was 44.8% and in Norway 45.3%.
      More than half of the Swedish GPs participating in this study stated that they
      had poor knowledge about chiropractic, while just a tenth of Norwegian GPs stated
      the same. Nearly all Norwegian GPs had some experience of chiropractic treatment
      whilst a fairly large number of the Swedish GPs said that they had no experience
      at all of chiropractic. It was twice as common for GPs in Norway to refer
      patients to a chiropractor as compared to Sweden. However, Swedish and Norwegian
      GPs agreed that chiropractors were competent to treat musculo-skeletal conditions
      with an adequate education to be part of mainstream medicine. CONCLUSIONS:
      Swedish and Norwegian GPs agree that chiropractors are competent to treat
      musculoskeletal conditions. However, there are many differences in GPs
      perceptions of chiropractic between the two countries and the overall picture
      indicates that chiropractic is more accepted and recognised as a health care
      profession in Norway.

PMID- 24128387
TI  - Simultaneous determination of concanavalin A and peanut agglutinin by dual-color
      quantum dots.
AB  - In this work, we designed a novel detection strategy to realize simultaneous
      determination of multiplex lectin by labeling glucosamine (G1) and galactosamine
      (G2) with different-colored semiconductor quantum dots (QDs). On the basis of the
      agglutination of the aminosugar-labeled QDs induced by the exclusive binding
      between the lectin and sugar on the QDs surfaces, the fluorescence emission of
      the QDs supernatant after centrifugation decreased with relevant lectin
      concentration [i.e., when concanavalin A (Con A) exists alone], only green color
      fluorescence emission from QDs-G1 supernatant decreased, so it is peanut
      agglutinin (PNA) and red color fluorescence emission from QDs-G2. Moreover, since
      QDs can be simultaneously excited with multiple fluorescence colors and have a
      larger Stokes shift than organic fluorophores, when both Con A and PNA are
      present in the sample, both of the green and red color fluorescence emission from
      QDs-G1 and QDs-G2 supernatant would decrease, thus realizing the simultaneous
      determination of Con A and PNA. The detection limits of Con A and PNA are 0.30
      and 0.18 nM (3sigma), respectively. Furthermore, the present detection method not
      only can determine the protein/lectins by fluorescence spectral method but also
      can realize visualization detection by UV lamp illumination. To the best of our
      knowledge, this is the first report of such analytical method in multiple and
      simultaneous lectin detection. 

PMID- 24128388
TI  - Inferring conjunctive probabilities from noisy samples: evidence for the
      configural weighted average model.
AB  - Judging whether multiple events will co-occur is an important aspect of everyday
      decision making. The underlying probabilities of occurrence are usually unknown
      and have to be inferred from experience. Using a rigorous, quantitative model
      comparison, we investigate how people judge the conjunctive probabilities of
      multiple events to co-occur. In 2 experiments, participants had to repeatedly
      choose between pairs of 2 conjunctive events (represented as 2 gambles). To
      estimate the probability that both events occur, they had access to a small
      sample of information. The 1st experiment consisted of a balanced set of gambles,
      whereas in the 2nd experiment, the gambles were constructed such that the models
      maximally differed in their predictions. A hierarchical Bayesian approach used
      for estimating the models' parameters and for testing the models against each
      other showed that the majority of participants were best described by the
      configural weighted average model. This model performed best in predicting
      people's choices, and it assumes that constituent probabilities are ranked by
      importance, weighted accordingly, and added up. The cognitive modeling approach
      provides an understanding of the cognitive processes underlying people's
      conjunctive probability judgments.

PMID- 24128389
TI  - Influence of renal function on long-term graft survival and patient survival in
      renal transplant recipients.
AB  - OBJECTIVES: Renal function post kidney transplantation is an outcome of interest
      for both clinicians and regulators evaluating immunosuppressive treatments post
      transplantation. The current review sought to provide a synopsis of currently
      available literature examining the relationship between post-transplantation
      renal function and long-term graft survival and patient survival. METHODS: A
      systematic literature review was performed using the PubMed, EMBASE and Cochrane
      Library databases. The search strategy was designed based on high level Medical
      Subject Heading (MeSH) terms and designed to capture studies published in English
      to 2012 and identified a total of 2683 unique hits; for inclusion studies were
      required to have >100 patients. Following two rounds of screening, a total of 27
      studies were included in the final review (26 of which were identified via the
      literature review and one study was identified via searches of the reference
      sections of included studies). RESULTS: The consensus among studies was that
      lower post-transplantation GFR, in particular 12 month GFR, was consistently and
      significantly associated with an increased risk for overall graft loss, death
      censored graft loss and all-cause mortality in both univariate and multivariate
      analyses. The magnitude of the association between reduced GFR and outcomes was
      greater for death-censored graft loss versus overall graft loss and for graft
      loss in comparison with overall patient mortality. The predictive utility of GFR
      alone in predicting long-term outcomes was reported to be limited. CONCLUSIONS:
      Lower GFR and greater rates of decline in GFR post-transplantation are associated
      with an increased risk for graft loss (overall and death-censored) and all-cause
      mortality; however, the predictive utility of GFR alone in predicting long-term
      outcomes is limited.

PMID- 24128390
TI  - [Etravirine in clinical practice: Experience in 151 non-naive patients].
AB  - BACKGROUND: There are limited data on etravirine (ETV) use in routine clinical
      practice. METHODS: The reasons, efficacy and tolerability of its use are
      retrospectively reviewed. RESULTS: Overall, 151patients started a regimen
      containing ETV. The main reasons for prescription were toxicity and virological
      failure. After a median follow-up of 16months 76.2% of the patients had an
      undetectable viral load. Patients with detectable HIV-RNA at baseline had a
      greater risk of failure (31.7% vs 18%; P=.05). CONCLUSION: ETV is safe, effective
      and durable.

PMID- 24128391
TI  - Characteristics related to TMJ arthralgia, visualized by magnetic resonance
      imaging (3.0 Tesla).
AB  - PATIENTS: Six women, with ages ranging from 52 to 64 years old, clinically
      evaluated (Research Diagnostic Criteria for Temporomandibular Disorders) by a
      single examiner were submitted to MRI (3.0 T). They had only arthralgia
      diagnosis. The images were evaluated by two radiologists who were not informed
      about the patients' clinical conditions, in which discs displacements,
      osteophytes and morphological irregularities, as well as completely normal
      images, i.e., without any characteristics were identified. DISCUSSION: TMJ
      arthralgia can be caused by various conditions, few of which are objectively
      observed when investigating its causes or diagnose temporomandibular disorders
      (TMD). In some cases, imaging exams can detect some conditions and magnetic
      resonance imaging (MRI) is commonly used for this purpose. Here, the MRI (3.0 T)
      enabled a detailed visualization of the structures of the TMJ, allowing the
      characterization of the symptomology in some cases. Despite, some images were
      completely normal. CONCLUSION: This case report detected some features seen on
      the MRI that justified a clinical diagnosis arthralgia, not associated with other
      clinical diagnosis. However, the detailed clinical examination should be
      sovereign even in the face of equipment with advanced technology.

PMID- 24128393
TI  - Mesoporous metal-nitrogen-doped carbon electrocatalysts for highly efficient
      oxygen reduction reaction.
AB  - A family of mesoporous nonprecious metal (NPM) catalysts for oxygen reduction
      reaction (ORR) in acidic media, including cobalt-nitrogen-doped carbon (C-N-Co)
      and iron-nitrogen-doped carbon (C-N-Fe), was prepared from vitamin B12 (VB12) and
      the polyaniline-Fe (PANI-Fe) complex, respectively. Silica nanoparticles, ordered
      mesoporous silica SBA-15, and montmorillonite were used as templates for
      achieving mesoporous structures. The most active mesoporous catalyst was
      fabricated from VB12 and silica nanoparticles and exhibited a remarkable ORR
      activity in acidic medium (half-wave potential of 0.79 V, only ~58 mV deviation
      from Pt/C), high selectivity (electron-transfer number >3.95), and excellent
      electrochemical stability (only 9 mV negative shift of half-wave potential after
      10,000 potential cycles). The unprecedented performance of these NPM catalysts in
      ORR was attributed to their well-defined porous structures with a narrow mesopore
      size distribution, high Brunauer-Emmett-Teller surface area (up to 572 m(2)/g),
      and homogeneous distribution of abundant metal-Nx active sites.

PMID- 24128392
TI  - The target gene of tae-miR164, a novel NAC transcription factor from the NAM
      subfamily, negatively regulates resistance of wheat to stripe rust.
AB  - microRNA (miRNA) participates in various physiological and biochemical processes
      in plants by regulating corresponding target genes. NAC [NAM (no apical
      meristem), ATAF (Arabidopsis transcription activation factor) and CUC (cup-shaped
      cotyledon)] transcription factors, usually as the targets of miR164, play
      important roles in the regulation of plant development and responses to abiotic
      and biotic stresses. In a previous study, the target gene of tae-miR164 in wheat
      was sequenced through degradome sequencing. In this study, we isolated the full
      length cDNA of the candidate target gene, which is a NAC transcription factor
      gene in the NAM subfamily, and designated it as TaNAC21/22 after bioinformatics
      analysis. The interaction between TaNAC21/22 and tae-miR164 was confirmed
      experimentally through co-transformation of both genes in tobacco leaves.
      Transcript accumulation of TaNAC21/22 and tae-miR164 showed contrasting divergent
      expression patterns in wheat response to Puccinia striiformis f. sp. tritici
      (Pst). TaNAC21/22 was confirmed to be located in the nucleus and could function
      as a transcriptional activator. Silencing of the individual gene showed that
      TaNAC21/22 negatively regulates resistance to stripe rust. These results indicate
      that the target of tae-miR164, a novel NAC transcription factor from the NAM
      subfamily of wheat, plays an important role in regulating the resistance of host
      plants to stripe rust. 

PMID- 24128394
TI  - Assessment of N2O emission from a photobioreactor treating ammonia-rich swine
      wastewater digestate.
AB  - This study investigated the interactions between naturally occurring bacteria and
      the microalgae Chlorella vulgaris within a lab scale photobioreactor treating
      ammonia-rich swine wastewater digestate effluent. Nitrification and
      denitrification were assessed by targeting ammonia monoxygenases (amoA), nitrate
      (narG), nitrite (nirS), nitric oxide (norB) and nitrous oxide (nosZ) reductases
      genes. Oxygen produced from microalgae photosynthesis stimulated nitrification.
      Under limiting carbon availability (i.e., <1.44 for mg TOC/mg NO2-N and 1.72 for
      mg TOC/mg NO3-N), incomplete denitrification led to accumulation of NO2 and NO3.
      Significant N2O emission (up to 118 MUg N2O-N) was linked to NO2 metabolism in
      Chlorella. The addition of acetate as external carbon source recovered
      heterotrophic denitrification activity suppressing N2O emission. Effluent methane
      concentrations trapped within photobioreactor was removed concomitantly with
      ammonia. Overall, closed photobioreactors can be built to effectively remove
      nitrogen and mitigate simultaneously greenhouse gases emissions that would occur
      otherwise in open microalgae-based wastewater treatment systems.

PMID- 24128395
TI  - Selective production of chemicals from biomass pyrolysis over metal chlorides
      supported on zeolite.
AB  - Direct biomass conversion into chemicals remains a great challenge because of the
      complexity of the compounds; hence, this process has attracted less attention
      than conversion into fuel. In this study, we propose a simple one-step method for
      converting bagasse into furfural (FF) and acetic acid (AC). In this method,
      bagasse pyrolysis over ZnCl2/HZSM-5 achieved a high FF and AC yield (58.10%) and
      a 1.01 FF/AC ratio, but a very low yield of medium-boiling point components.
      However, bagasse pyrolysis using HZSM-5 alone or ZnCl2 alone still remained large
      amounts of medium-boiling point components or high-boiling point components. The
      synergistic effect of HZSM-5 and ZnCl2, which combines pyrolysis, zeolite
      cracking, and Lewis acid-selective catalysis results in highly efficient bagasse
      conversion into FF and AC. Therefore, our study provides a novel, simple method
      for directly converting biomass into high-yield useful chemical. 

PMID- 24128396
TI  - Responses of anaerobic granule and flocculent sludge to ceria nanoparticles and
      toxic mechanisms.
AB  - Effects of CeO2-NPs on anaerobic fermentation were investigated from the
      processes of acidification and methanation with anaerobic granule sludge and
      anaerobic flocculent sludge as the targets. Results showed that acidification
      process was more sensitive to CeO2-NPs than methanation process. Both types of
      sludge produced less short-chain fatty acid compared to the control, with a
      reduction of 15-19% for the flocculent sludge at the dosage of 5, 50 and 150 mg
      CeO2-NPs/g-VSS, and a reduction of 35% for the granular sludge at 150 mg CeO2
      NPs/g-VSS. CeO2-NPs caused no inhibition to methanation process. Most of CeO2-NPs
      distributed on the surface of sludge as revealed by fluorescence labeled CeO2
      NPs. The toxicity of CeO2-NPs to anaerobic sludge did not result from reactive
      oxygen species. Physical penetration and membrane reduction may be important
      toxic mechanisms.

PMID- 24128397
TI  - Alkaline pretreatment for enhancement of biogas production from banana stem and
      swine manure by anaerobic codigestion.
AB  - The objective of this research was to propose and investigate the availability of
      digested banana stem (BS) to produce biogas. Squeezed BS with less moisture
      content was used for biogas production through a combination of NaOH
      pretreatment, solid-state fermentation, and codigestion technologies. NaOH doses
      were optimized according to biogas fermentation performance, and the best dose
      was 6% (by weight) based on the total solid (TS) of BS. Under this condition, the
      lignin, cellulose, and hemicellulose contents decreased from 18.36%, 32.36% and
      14.6% to 17.10%, 30.07%, and 10.65%, respectively, after pretreatment. After
      biogas digestion, TS and volatile solid (VS) reductions of the codigestion were
      48.5% and 70.4%, respectively, and the biogas and methane yields based on VS
      loading were 357.9 and 232.4 mL/g, which were 12.1% and 21.4%, respectively,
      higher than the control. Results indicated that the proposed process could be an
      effective method for using BS to produce biogas.

PMID- 24128398
TI  - Enhancement of Taihu blue algae anaerobic digestion efficiency by natural
      storage.
AB  - Taihu blue algae after different storage time from 0 to 60 d were anaerobic
      fermented to evaluate their digestibility and process stability. Results showed
      that anaerobic digestion (AD) of blue algae under 15 d natural storage led to the
      highest CH4 production of 287.6 mL g(-1) VS at inoculum substrate ratio 2.0,
      demonstrating 36.69% improvement comparing with that from fresh algae. Storage of
      blue algae led to cell death, microcystins (MCs) release and VS reduction by
      spontaneous fermentation. However, it also played an important role in removing
      algal cell wall barrier, pre-hydrolysis and pre-acidification, leading to the
      improvement in CH4 yield. Closer examination of volatile fatty acids (VFA)
      variation, VS removal rates and key enzymes change during AD proved short storage
      time (<= 15 d) of blue algae had higher efficiencies in biodegradation and
      methanation. Furthermore, AD presented significant biodegradation potential for
      MCs released from Taihu blue algae.

PMID- 24128399
TI  - Rapid synthesis of propyl caffeate in ionic liquid using a packed bed enzyme
      microreactor under continuous-flow conditions.
AB  - Propyl caffeate has the highest antioxidant activity among caffeic acid alkyl
      esters, but its industrial production via enzymatic transesterification in batch
      reactors is hindered by a long reaction time (24h). To develop a rapid process
      for the production of propyl caffeate in high yield, a continuous-flow
      microreactor composed of a two-piece PDMS in a sandwich-like microchannel
      structure was designed for the transesterification of methyl caffeate and 1
      propanol catalyzed by Novozym 435 in [B mim][CF3SO3]. The maximum yield (99.5%)
      in the microreactor was achieved in a short period of time (2.5h) with a flow
      rate of 2 MUL/min, which kinetic constant Km was 16 times lower than that of a
      batch reactor. The results indicated that the use of a continuous-flow packed bed
      enzyme microreactor is an efficient method of producing propyl caffeate with an
      overall yield of 84.0%.

PMID- 24128400
TI  - Effects of green liquor pretreatment on the chemical composition and enzymatic
      digestibility of rice straw.
AB  - Green liquor (Na2S+Na2CO3, GL) pretreatment is a proven pathway to improve the
      enzymatic saccharification for the production of bioethanol. In this work, the
      effects of GL pretreatment on the chemical composition and enzymatic
      digestibility of rice straw at various total titratable alkali (TTA) charge and
      temperature were investigated. The GL pretreatment showed excellent performance
      in high polysaccharides retention and delignification selectivity. Under the
      optimized GL pretreatment condition (4% TTA charge, 20% sulfidity and 140 degrees
      C), 92.5% of glucan, 82.4% of xylan and 81.6% of arabinan in rice straw were
      recovered with a delignification of 39.4%. The maximum sugar yields of 83.9%,
      69.6% and 78.0%, respectively for glucan, xylan and total sugar, were achieved at
      the same GL pretreatment condition with an enzyme loading of 40 FPU/g-substrate.
      The results suggested that GL pretreatment is a practicable method for rice straw
      to enhance enzymatic saccharification for bioethanol production.

PMID- 24128401
TI  - Activated carbon from biochar: influence of its physicochemical properties on the
      sorption characteristics of phenanthrene.
AB  - The relationship between physicochemical properties of biochar-based activated
      carbons and its adsorption was investigated using an aromatic model compound,
      phenanthrene. Solid-state (13)C NMR analysis indicated more condensed aromatic
      structures when pyrolysis temperature increased or after activation process
      induced. The increasing aromaticity and non-protonated carbon fraction of the
      activated biochar treated at 300 degrees C amounted to 14.7% and 24.0%,
      respectively, compared to 7.4% and 4.4% for biochar treated at 700 degrees C. The
      surface area and pore volume were reduced with the increase in pyrolysis
      temperature, but increased after activation. Surface characteristics correlated
      with the initial sorption rate and equilibrium concentration of phenanthrene, but
      not with the aromaticity. Solid-state (2)H NMR for phenanthrene-d10 saturated
      activated biochars, however, showed substantial difference in molecular mobility,
      which might be due to the high aromaticity of the activated biochars. Overall,
      these results provide an opportunity to manipulate the characteristics of biomass
      based adsorbents based on the application needs. 

PMID- 24128402
TI  - Predicting kinetic model of biogas production and biodegradability organic
      materials: biogas production from vinasse at variation of COD/N ratio.
AB  - The biogas fermentation of vinasse (TS 7.015 +/- 0.007%) was investigated within
      a wide range of COD (Chemical Oxygen Demand)/N (Total Nitrogen) ratio. Urea (46%
      nitrogen content) was added into substrate to adjust COD/N ratio of 400/7-700/7.
      This study used batch anaerobic digesters in laboratory-scale that were operated
      at room temperature in 60 days. The results showed that control variable, 400/7,
      500/7, 600/7, 700/7 generated total biogas of 107.45, 123.87, 133.82, 139.17,
      113.27 mL/g COD and had the value of COD removal of 31.274 +/- 0.887, 33.483 +/-
      0.266, 36.573 +/- 1.689, 38.088 +/- 0.872, 32.714 +/- 0.881%, respectively.
      Variable with COD/N ratio of 600/7 was the best variable. In the kinetic model of
      biogas production, variable with COD/N of 600/7 had kinetic constant of A (mL/g
      COD), MU (mL/g COD.day), lambda (days) of 132.580, 15.200, 0.213, respectively.
      The model equation of kinetic of biodegradability organic materials obtained was
      [formula in text].

PMID- 24128403
TI  - Recirculation or artificial aeration in vertical flow constructed wetlands: a
      comparative study for treating high load wastewater.
AB  - Vertical subsurface-flow constructed wetlands at pilot-scale have been applied to
      treat high hydraulic and organic loads by implementing the following
      configurations: (1) intermittent recirculation of the treated wastewater from the
      bottom to the top of the bed, (2) intermittent artificial aeration supplied at
      the bottom of the bed and (3) the combination of both. These configurations were
      operated with a saturated bottom layer for a 6h-treatment phase, followed by a
      free drainage phase prior to a new feeding. COD removal efficiency was 85-90% in
      all the configurations and removed loads were 54-70 gCOD m(-2)d(-1). The aerated
      and recirculated wetland resulted in a higher total nitrogen removal (8.6 gN m(
      2)d(-1)) due to simultaneous nitrification/denitrification, even in the presence
      of intermittent aeration (6.8 Nm(3)m(-2)d(-1)). The extra investment needed for
      implementing aeration/recirculation would be compensated for by a reduction of
      the surface area per population equivalent, which decreased to 1.5m(2)/PE.

PMID- 24128404
TI  - Direct and efficient xylitol production from xylan by Saccharomyces cerevisiae
      through transcriptional level and fermentation processing optimizations.
AB  - In this study, four engineered Saccharomyces cerevisiae carrying xylanase, beta
      xylosidase and xylose reductase genes by different transcriptional regulations
      were constructed to directly convert xylan to xylitol. According to the results,
      the high-copy number plasmid required a rigid selection for promoter
      characteristics, on the contrast, the selection of promoters could be more
      flexible for low-copy number plasmid. For cell growth and xylitol production,
      glucose and galactose were found more efficient than other sugars. The semi
      aerobic condition and feeding of co-substrates were taken to improve the yield of
      xylitol. It was found that the strain containing high-copy number plasmid had the
      highest xylitol yield, but it was sensitive to the change of fermentation.
      However, the strain carrying low-copy number plasmid was more adaptable to
      different processes. By optimization of the transcriptional regulation and
      fermentation processes, the xylitol concentration could be increased of 1.7 folds
      and the yield was 0.71 g xylitol/g xylan.

PMID- 24128405
TI  - Utilization of rice husks modified by organomultiphosphonic acids as low-cost
      biosorbents for enhanced adsorption of heavy metal ions.
AB  - Novel biosorbent materials (RH-2 and RH-3) obtained from agricultural waste
      materials rice husks (RH-1) were successfully developed through fast and facile
      esterification reactions with hydroxylethylidenediphosphonic acid and
      nitrilotrimethylenetriphosphonic acid, respectively. The present paper reported
      the feasibility of using RH-1, RH-2 and RH-3 for removal of heavy metals from
      simulated wastewater, the results revealed that the adsorption property of
      functionalized rice husks with organotriphosphonic acid RH-3 for Au(III) was very
      excellent, especially for gold ions. The combined effect of initial solution pH,
      RH-3 dosage and initial Au(III) concentration was investigated using response
      surface methodology (RSM), the results showed that initial Au(III) concentration
      exerted stronger influence on Au(III) uptake than initial pH and biomass dosage.
      The analysis of variance (ANOVA) of the quadratic model demonstrated that the
      model was highly significant, and under the optimum process conditions, the
      maximum adsorption capacity could reach 3.25 +/- 0.07 mmol/g that is higher than
      other reported adsorbents.

PMID- 24128406
TI  - Considerations for community-based mHealth initiatives: insights from three
      Beacon Communities.
AB  - Mobile health (mHealth) is gaining widespread attention for its potential to
      engage patients in their health and health care in their daily lives. Emerging
      evidence suggests that mHealth interventions can be used effectively to support
      behavior change, but numerous challenges remain when implementing these programs
      at the community level. This paper provides an overview of considerations when
      implementing community-based mHealth initiatives, based on the experiences of
      three Beacon Communities across the United States that have launched text
      messaging (short message service, SMS) pilot programs aimed at diabetes risk
      reduction and disease management. The paper addresses lessons learned and
      suggests strategies to overcome challenges related to developing text message
      content, conducting marketing and outreach, enrolling participants, engaging
      providers, evaluating program effectiveness, and sustaining and scaling the
      programs. 

PMID- 24128407
TI  - Clinical staging: a necessary step in the development of improved animal models
      of mood disturbance?
AB  - Recently, it has been suggested that the clinical staging approach be considered
      a serious alternative framework for conceptualising mood related psychopathology.
      The fundamental difference between clinical staging and the now dominant
      categorical diagnostic framework is that the entire illness trajectory becomes
      relevant, as opposed to simply the end-stage. The concept of disease trajectory
      has significant implications for animal models of psychopathology, and
      particularly for animal models of depression. This article will introduce and
      discuss the implications of the clinical staging approach for those undertaking
      research using animal models of mood disturbance. 

PMID- 24128408
TI  - Undercalibrating in goal-directed therapy?

PMID- 24128409
TI  - Degree of discrepancy between HbA1c and glycemia in variant hemoglobin is smaller
      when HbA1c is measured by new-type Arkray HPLC compared with old-type HPLC.
AB  - OBJECTIVES: Although variant hemoglobin mainly demonstrates inappropriate HbA1c
      values measured by high-performance liquid chromatography (HPLC), these values
      differ depending on the HPLC model. In the 1990s, old-type HPLC models were
      replaced with new-type HPLC models which could separate stable HbA1c from labile
      HbA1c and modified hemoglobin. This study compared HbA1c values in subjects with
      variant hemoglobin measured using old-type Arkray HPLC (HA-8150) and new-type
      Arkray HPLC (HA-8160 or HA-8180). DESIGN AND METHODS: This study included non
      diabetic subjects with apparently low HbA1c values who had variant hemoglobins
      due to a beta-chain heterozygous mutation. HbA1c was measured by old-type HPLC in
      28 subjects with 12 variant hemoglobins (group 1) and new-type HPLC in six
      subjects with four variant hemoglobins (group 2). When HbA1c was measured by HPLC
      (HPLC-HbA1c), HbA1c measured by immunoassay (IA-HbA1c) and glycated albumin (GA)
      were also measured. RESULTS: IA-HbA1c and GA did not significantly differ between
      both groups. However, HPLC-HbA1c in group 2 was significantly higher than that in
      group 1 (group 1: 2.9 +/- 0.7% vs. group 2: 3.7 +/- 0.2%, P = 0.006).
      CONCLUSIONS: When HbA1c in subjects with variant hemoglobin is measured by new
      type Arkray HPLC, the degree of discrepancy between HbA1c and glycemia is smaller
      compared with that measured by old-type HPLC.

PMID- 24128410
TI  - New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold:
      synthesis, antiproliferative activities against melanoma cell lines, kinase
      inhibition, and in silico studies.
AB  - Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8
      amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative
      activities against ten melanoma cell lines were tested. Compounds 1l, 2l, 3c, and
      4c showed the highest potency against A375P cell line with IC50 values in sub
      micromolar scale. Compound 4c was equipotent to Vemurafenib against A375P. In
      addition, compounds 1l, 2a, and 2l showed high potency over the NCI-9 tested
      melanoma cell line panel. The IC50 values of compounds 1l and 2l were in 2-digit
      nanomolar scale over four and five cell lines, respectively. Compound 2l showed
      high, dose-dependent inhibition of ERK kinase. ADME profiling showed that
      compounds 1l, 2l, 3c, 4c, and 5b are estimated to be orally bioavailable. 

PMID- 24128411
TI  - Maternal and fetal alternative complement pathway activation in early severe
      preeclampsia.
AB  - PROBLEM: We sought to determine whether alternative complement activation
      fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood
      in cases of severe preeclampsia (PE) compared with normotensive controls. METHOD
      OF STUDY: This was a cross-sectional study of women admitted at >=24 weeks
      gestation with or without severe PE. Maternal plasma was collected at the time of
      enrollment. Umbilical venous cord and intervillous space blood were collected at
      delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared
      between cases and controls. RESULTS: Median Bb levels were higher in the maternal
      plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 +/- 1.03
      versus 0.65 +/- 0.23 MUg/mL, P < 0.001. In umbilical venous plasma, Bb levels
      were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48
      +/- 1.40 versus 1.01 +/- 0.57 MUg/mL, P = 0.01. CONCLUSION: Activation fragment
      Bb is increased in the maternal and umbilical venous blood of cases of severe PE
      when compared with normotensive controls. These data provide support for
      alternative complement pathway involvement in the pathogenesis of severe PE and
      demonstrate that alternative complement activation occurs not only in the
      maternal but also in the fetal compartment.

PMID- 24128412
TI  - The exostosin family: proteins with many functions.
AB  - Heparan sulfates are complex sulfated molecules found in abundance at cell
      surfaces and in the extracellular matrix. They bind to and influence the activity
      of a variety of molecules like growth factors, proteases and morphogens and are
      thus involved in various cell-cell and cell-matrix interactions. The mammalian
      EXT proteins have glycosyltransferase activities relevant for HS chain
      polymerization, however their exact role in this process is still confusing. In
      this review, we summarize current knowledge about the biochemical activities and
      some proposed functions of the members of the EXT protein family and their roles
      in human disease. 

PMID- 24128413
TI  - Liver stiffness-based optimization of hepatocellular carcinoma risk score in
      patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: CU-HCC score is accurate to predict hepatocellular carcinoma
      (HCC) in chronic hepatitis B (CHB) patients. However, diagnosis of cirrhosis may
      be incorrect based on ultrasonography, leading to some errors in HCC prediction.
      This study aimed to evaluate the accuracy of LSM-HCC score, refined from CU-HCC
      score with liver stiffness measurement (LSM) using transient elastography to
      predict HCC. METHODS: A prospective cohort study of 1555 consecutive CHB patients
      referred for transient elastography examination; 1035 and 520 patients randomly
      assigned to training and validation cohorts, respectively. Clinical cirrhosis of
      CU-HCC score was substituted by LSM and analyzed with multivariable Cox
      regression analysis with other parameters. RESULTS: During a mean follow-up of 69
      months, 38 patients (3.7%) in the training cohort and 17 patients (3.4%) in the
      validation cohort developed HCC. A new LSM-HCC score composed of LSM, age, serum
      albumin and hepatitis B virus (HBV) DNA levels were derived, which ranges from 0
      to 30. Areas under receiver operating characteristic curves of LSM-HCC score were
      higher than those of CU-HCC score (0.83-0.89 vs. 0.75-0.81). By applying the
      cutoff value of 11, the score excluded future HCC with high negative predictive
      value (99.4%-100%) at 5 years. CONCLUSIONS: LSM-HCC score constructed from LSM,
      age, serum albumin and HBV DNA level is accurate to predict HCC in CHB patients.

PMID- 24128414
TI  - Characteristics, risk factors, and mortality of cirrhotic patients hospitalized
      for hepatic encephalopathy with and without acute-on-chronic liver failure
      (ACLF).
AB  - BACKGROUND & AIMS: In spite of the high incidence of hepatic encephalopathy (HE)
      in cirrhosis, there are few observational studies. METHODS: We performed an
      analysis to define the characteristics of HE and associated features using the
      database of the Canonic Study. Clinical, laboratory and survival data of 1348
      consecutive cirrhotic patients admitted with an acute decompensation were
      compared according to the presence (n=406) or absence of HE and of acute-on
      chronic liver failure (ACLF) (n=301). RESULTS: HE development was independently
      associated with previous HE episodes; survival probabilities worsen in relation
      to the presence and grade of HE. There were marked differences between HE
      associated (n=174) and not associated (n=286) to ACLF. HE not associated with
      ACLF occurred in older cirrhotics, inactive drinkers, without severe liver
      failure or systemic inflammatory reaction and in relation to diuretic use. In
      contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently
      alcoholics, with severe liver failure and systemic inflammatory reaction, and in
      relation to bacterial infections, active alcoholism and/or dilutional
      hyponatremia. Prognosis was relatively preserved in the first and extremely poor
      in the second group. Independent risk factors of mortality in patients with HE
      were age, bilirubin, INR, creatinine, sodium, and HE grade. CONCLUSIONS: In
      cirrhosis, previous HE identifies a subgroup of patients that is especially
      vulnerable for developing new episodes of HE. The course of HE appears to be
      different according to the presence of ACLF.

PMID- 24128415
TI  - 1 and 5 year survival estimates for people with cirrhosis of the liver in
      England, 1998-2009: a large population study.
AB  - BACKGROUND & AIMS: Large, population-based studies that have included the full
      spectrum of cirrhosis estimating survival, taking into account time-at-risk are
      lacking. We aimed to report 1- and 5-year average survival rates for people with
      cirrhosis to be used in a clinical and healthcare policy setting. METHODS: We
      used the Clinical Practice Research Datalink and linked English Hospital Episode
      Statistics to identify adult cases of cirrhosis from January 1998 to December
      2009. We estimated 1- and 5-year survival according to whether time-at-risk was
      ambulatory or followed an emergency hospital admission related to liver disease,
      stratified by age, sex, and aetiology to be used in a clinical setting. We used a
      multivariate Cox-proportional hazards model with a time-varying variable,
      adjusted for Baveno IV stage of cirrhosis at diagnosis, age, aetiology, and sex.
      RESULTS: We identified 5118 incident cases. Average survival probabilities at 1-
      and 5-years were 0.84 (95% CI 0.83-0.86) and 0.66 (95% CI 0.63-0.68) for the
      ambulatory group and 0.55 (95% CI 0.53-0.57) and 0.31 (95% CI 0.29-0.33)
      following hospitalisation, respectively. A hospital admission at diagnosis or
      subsequently for liver disease substantially impaired prognosis independent of
      stage of cirrhosis (HR=2.78, 95% CI 2.53, 3.06). CONCLUSIONS: Emergency
      hospitalisation for liver disease heralds a downturn in a patient's outlook
      independent of their stage of cirrhosis. Our results provide population-based
      clinically translatable estimates of prognosis for the purposes of healthcare
      delivery and planning and communication to patients.

PMID- 24128416
TI  - PTPRO plays a dual role in hepatic ischemia reperfusion injury through feedback
      activation of NF-kappaB.
AB  - BACKGROUND & AIMS: Nuclear factor-kappaB (NF-kappaB) activation in hepatocytes
      and macrophages appeared as a double-edged-sword in hepatic ischemia reperfusion
      (IR) injury. Protein tyrosine phosphatase receptor type O (PTPRO) was recently
      identified as a potential activator of c-Src, which can in turn activate the NF
      kappaB pathway. In this study, we aimed to determine the change and function of
      PTPRO in hepatocytes and macrophages during IR. METHODS: Clinical patients with
      benign liver condition undergoing liver surgery were recruited in our study. Wild
      type (WT) and ptpro(-/-) C57BL/6 mice were processed to construct hepatic IR
      models. Isolated mouse hepatocytes and macrophages were treated with peroxide or
      TNFalpha in vitro. RESULTS: In human and mouse IR models, PTPRO level was
      decreased in the early phase but reversed in the late phase. In vitro studies
      demonstrated that NF-kappaB up-regulated PTPRO transcription. Using ptpro(-/-)
      mice and primary cells, we found that PTPRO deficiency resulted in reduction of
      NF-kappaB activation in both hepatocytes and macrophages and was correlated to c
      Src phosphorylation; PTPRO in hepatocytes alleviated, but PTPROt in macrophages
      exacerbated IR injury. CONCLUSIONS: PTPRO activates NF-kappaB in a positive
      feedback manner, and plays a dual role in hepatic IR injury.

PMID- 24128417
TI  - Victory and defeat at Heraclea - treating hepatitis C infection following liver
      transplantation with telaprevir and boceprevir.

PMID- 24128418
TI  - Genetically humanized mice recapitulate the entire hepatitis C virus life cycle.

PMID- 24128419
TI  - Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal
      recessive lethal fetal ciliopathy phenotype.
AB  - Gene discovery using massively parallel sequencing has focused on phenotypes
      diagnosed postnatally such as well-characterized syndromes or intellectual
      disability, but is rarely reported for fetal disorders. We used family-based
      whole-exome sequencing in order to identify causal variants for a recurrent
      pattern of an undescribed lethal fetal congenital anomaly syndrome. The clinical
      signs included intrauterine growth restriction (IUGR), severe microcephaly, renal
      cystic dysplasia/agenesis and complex brain and genitourinary malformations. The
      phenotype was compatible with a ciliopathy, but not diagnostic of any known
      condition. We hypothesized biallelic disruption of a gene leading to a defect
      related to the primary cilium. We identified novel autosomal recessive truncating
      mutations in KIF14 that segregated with the phenotype. Mice with autosomal
      recessive mutations in the same gene have recently been shown to have a
      strikingly similar phenotype. Genotype-phenotype correlations indicate that the
      function of KIF14 in cell division and cytokinesis can be linked to a role in
      primary cilia, supported by previous cellular and model organism studies of
      proteins that interact with KIF14. We describe the first human phenotype, a novel
      lethal ciliary disorder, associated with biallelic inactivating mutations in
      KIF14. KIF14 may also be considered a candidate gene for allelic viable ciliary
      and/or microcephaly phenotypes. 

PMID- 24128420
TI  - Optimizing antimicrobial prescribing: Are clinicians following national trends in
      methicillin-resistant staphylococcus aureus (MRSA) infections rather than local
      data when treating MRSA wound infections.
AB  - BACKGROUND: Clinicians often prescribe antimicrobials for outpatient wound
      infections before culture results are known. Local or national MRSA rates may be
      considered when prescribing antimicrobials. If clinicians prescribe in response
      to national rather than local MRSA trends, prescribing may be improved by making
      local data accessible. We aimed to assess the correlation between outpatient
      trends in antimicrobial prescribing and the prevalence of MRSA wound infections
      across local and national levels. METHODS: Monthly MRSA positive wound culture
      counts were obtained from The Surveillance Network, a database of antimicrobial
      susceptibilities from clinical laboratories across 278 zip codes from 1999-2007.
      Monthly outpatient retail sales of linezolid, clindamycin, trimethoprim
      sulfamethoxazole and cephalexin from 1999-2007 were obtained from the IMS Health
      XponentTM database. Rates were created using census populations. The proportion
      of variance in prescribing that could be explained by MRSA rates was assessed by
      the coefficient of determination (R2), using population weighted linear
      regression. RESULTS: 107,215 MRSA positive wound cultures and 106,641,604
      antimicrobial prescriptions were assessed. The R2 was low when zip code-level
      antimicrobial prescription rates were compared to MRSA rates at all levels. State
      level prescriptions of clindamycin and linezolid were not correlated with state
      MRSA rates. The variance in state-level prescribing of clindamycin and linezolid
      was correlated with national MRSA rates (clindamycin R2 = 0.17, linezolid R2 =
      0.22). CONCLUSIONS: Clinicians may rely on national, not local MRSA data when
      prescribing clindamycin and linezolid for wound infections. Providing local
      resistance data to prescribing clinicians may improve antimicrobial prescribing
      and would be a possible target for future interventions.

PMID- 24128421
TI  - Positive and negative meanings are simultaneously ascribed to colorectal cancer:
      relationship to quality of life and psychosocial adjustment.
AB  - OBJECTIVE: Experiencing cancer can give rise to existential concerns causing
      great distress, and consequently drive individuals to make sense of what cancer
      may mean to their lives. To date, meaning-based research in the context of cancer
      has largely focused on one possible outcome of this process, the emergence of
      positive meanings (e.g. post-traumatic growth). However, negative meanings may
      also be ascribed to cancer, simultaneously with positive meanings. This study
      focused on the nature of the co-existence of positive and negative meanings in a
      sample of individuals diagnosed with colorectal cancer to find out whether
      negative meaning had an impact on quality of life and psychosocial adjustment
      above and beyond positive meaning. METHODS: Participants were given
      questionnaires measuring meaning-made, quality of life, and psychological
      distress. Semi structured interviews were conducted with a subgroup from the
      original sample. RESULTS: Hierarchical multiple regression analyses revealed that
      negative meaning-made (i.e. helplessness) was a significant predictor of poor
      quality of life and increased levels of depression/anxiety above and beyond
      positive meaning-made (i.e. life meaningfulness, acceptance, and perceived
      benefits). Correlational analyses and interview data revealed that negative
      meaning-made was mainly associated with physical and functional disability, while
      positive meaning-made was mostly related to emotional and psychological well
      being. SIGNIFICANCE OF RESULTS: Meanings of varying valence may simultaneously be
      ascribed to cancer as it impacts different life dimensions, and they may
      independently influence quality of life and psychosocial adjustment. The presence
      of positive meaning was not enough to prevent the detrimental effects of negative
      meaning on psychosocial adjustment and quality of life among individuals taking
      part in this study. Future attention to negative meaning is warranted, as it may
      be at least as important as positive meaning in predicting psychosocial
      adjustment and quality of life following a cancer diagnosis.

PMID- 24128422
TI  - Progesterone elicits an inhibitory effect upon LPS-induced innate immune response
      in pre-labor human amniotic epithelium.
AB  - PROBLEM: Infection of human fetal membranes elicits secretion of pro-inflammatory
      modulators through its innate immune capacities. We investigated the effect of
      lipopolysacharide (LPS) and progesterone (P4) upon expression of TLR-4/MyD88,
      TNFalpha, IL-6, IL-8, IL-10, and HBD2 on the human amniotic epithelium. METHOD OF
      STUDY: Explants of the human amniotic epithelium were pre-treated with 0.01, 0.1,
      and 1.0 MUM of P4; then cotreated with 1000 ng/mL LPS. TLR-4 was immuno-detected,
      and concentrations of MyD88, TNFalpha, IL-6, IL-8, IL-10, and HBD2 were
      quantified by ELISA. RESULTS: P4 significantly reduced the expression of LPS
      induced TLR-4/MyD88. LPS increased the concentrations of TNFalpha, IL-6, IL-8, IL
      10, and HBD2 by factors of 30-, eight, three, three, and fivefold, respectively.
      P4 at 1.0 MUM was the most effective dose to blunt the secretion of TNFalpha, IL
      6, and HBD-2. RU-486 blocks the effect of P4. CONCLUSION: P4 inhibited LPS
      induced TLR-4/MyD88 and pro-inflammatory factors in the human amniotic
      epithelium. These results could explain partially how P4 can protect the amniotic
      region of fetal membranes and generate a compensatory mechanism that limits the
      secretion of pro-inflammatory modulators, which could jeopardize the immune
      privilege during pregnancy.

PMID- 24128423
TI  - Image guidance protocols: balancing imaging parameters against scan time.
AB  - OBJECTIVE: Optimisation of imaging protocols is essential to maximise the use of
      image-guided radiotherapy. This article evaluates the time for daily online
      imaging with TomoTherapy(r) (Accuray(r), Sunnyvale, CA), separating mechanical
      scan acquisition from radiographer-led image matching, to estimate the time
      required for a clinical research study (VoxTox). METHODS: Over 5 years, 18 533
      treatments were recorded for 3 tumour sites of interest (prostate, head and neck
      and central nervous system). Data were collected for scan length, number of CT
      slices, slice thickness, scan acquisition time and image matching time. RESULTS:
      The proportion of coarse thickness scans increased over time, with a move of
      making coarse scans as the default. There was a strong correlation between scan
      time and scan length. Scan acquisition requires 40 s of processing time. For
      coarse scans, each additional centimetre requires 8 s for acquisition. Image
      matching takes approximately 1.5 times as long, so each additional centimetre
      needs 20 s extra in total. Modest changes to the imaging protocol have minimal
      impact over the course of the day. CONCLUSION: This work quantified the effect of
      changes to clinical protocols required for research. The results have been found
      to be reassuring in the busy National Institutes of Health department. ADVANCES
      IN KNOWLEDGE: This novel method of data collection and analysis provides evidence
      of the minimal impact of research on clinical turnover. Whilst the data relate
      specifically to TomoTherapy, some aspects may apply to other platforms in the
      future.

PMID- 24128425
TI  - Knowing a sexual assault victim or perpetrator: a stratified random sample of
      undergraduates at one university.
AB  - Rape awareness and prevention programs are common on college campuses and a
      potentially useful way to reach large numbers of young adults. One largely
      unexamined potential mediator or moderator of program effectiveness is the
      personal knowledge of student audiences. In this study, we assess the prevalence
      of knowing a victim and, notably, a perpetrator of sexual assault. A stratified
      random sample of 2,400 undergraduates was recruited for an online survey about
      sexual assault. A total of 53.5% participated and yielded a sample representative
      of the student body. Sixteen questions were modified from the Sexual Experiences
      Survey to assess whether participants knew a victim of any one of eight types of
      sexual assault. Findings indicate that students begin college with considerable
      personal knowledge of sexual assault victimization and perpetration. Nearly two
      thirds (64.5%) reported that they know one or more women who were a victim of any
      one of eight types of sexual assault, and over half (52.4%) reported that they
      know one or more men who perpetrated any of the types of sexual assault. Most
      students reported knowing victims and perpetrators of multiple types of assault.
      Knowledge varied substantially by gender and ethnicity. Students' preexisting
      personal knowledge should be included in assessments of program effectiveness
      and, ideally, in program design. 

PMID- 24128424
TI  - Cerebral tissue oxygenation impairment during experimental cerebral malaria.
AB  - Ischemia and hypoxia have been implicated in cerebral malaria (CM) pathogenesis,
      although direct measurements of hypoxia have not been conducted. C57BL/6 mice
      infected with Plasmodium berghei ANKA (PbA) develop a neurological syndrome known
      as experimental cerebral malaria (ECM), whereas BALB/c mice are resistant to ECM.
      In this study, intravital microscopy methods were used to quantify hemodynamic
      changes, vascular/tissue oxygen (O2) tension (PO2), and perivascular pH in vivo
      in ECM and non-ECM models, employing a closed cranial window model. ECM mice on
      day 6 of infection showed marked decreases in pial blood flow, vascular
      (arteriolar, venular), and perivascular PO2, perivascular pH, and systemic
      hemoglobin levels. Changes were more dramatic in mice with late-stage ECM
      compared with mice with early-stage ECM. These changes led to drastic decreases
      in O2 delivery to the brain tissue. In addition, ECM animals required a greater
      PO2 gradient to extract the same amount of O2 compared with non-infected animals,
      as the pial tissues extract O2 from the steepest portion of the blood O2
      equilibrium curve. ECM animals also showed increased leukocyte adherence in
      postcapillary venules, and the intensity of adhesion was inversely correlated
      with blood flow and O2 extraction. PbA-infected BALB/c mice displayed no
      neurological signs on day 6 and while they did show changes similar to those
      observed in C57BL/6 mice (decreased pial blood flow, vascular/tissue PO2,
      perivascular pH, hemoglobin levels), non-ECM animals preserved superior perfusion
      and oxygenation compared with ECM animals at similar anemia and parasitemia
      levels, resulting in better O2 delivery and O2 extraction by the brain tissue. In
      conclusion, direct quantitative assessment of pial hemodynamics and oxygenation
      in vivo revealed that ECM is associated with severe progressive brain tissue
      hypoxia and acidosis.

PMID- 24128426
TI  - Assessing the reliability and validity of the Chinese Sexual Assault Symptom
      Scale (C-SASS): scale development and validation.
AB  - The purpose of this research is to establish and verify the psychometric and
      structural properties of the self-report Chinese Sexual Assault Symptom Scale (C
      SASS) to assess the trauma experienced by Chinese victims of sexual assault. An
      earlier version of the C-SASS was constructed using a modified list of the same
      trauma symptoms administered to an American sample and used to develop and
      validate the Sexual Assault Symptom Scale II (SASS II). The rationale of this
      study is to revise the earlier version of the C-SASS, using a larger and more
      representative sample and more robust statistical analysis than in earlier
      research, to permit a more thorough examination of the instrument and further
      confirm the dimensions of sexual assault trauma in Chinese victims of rape. In
      this study, a sample of 418 victims from northern Taiwan was collected to confirm
      the reliability and validity of the C-SASS. Exploratory factor analysis yielded
      five common factors: Safety Fears, Self-Blame, Health Fears, Anger and Emotional
      Lability, and Fears About the Criminal Justice System. Further tests of the
      validity and composite reliability of the C-SASS were provided by the structural
      equation modeling (SEM). The results indicated that the C-SASS was a brief,
      valid, and reliable instrument for assessing sexual assault trauma among Chinese
      victims in Taiwan. The scale can be used to evaluate victims in sexual assault
      treatment centers around Taiwan, as well as to capture the characteristics of
      sexual assault trauma among Chinese victims. 

PMID- 24128428
TI  - 'Herbal' but potentially hazardous: an analysis of the constituents and smoke
      emissions of tobacco-free waterpipe products and the air quality in the cafes
      where they are served.
AB  - BACKGROUND: There are limited data on the composition and smoke emissions of
      'herbal' shisha products and the air quality of establishments where they are
      smoked. METHODS: Three studies of 'herbal' shisha were conducted: (1) samples of
      'herbal' shisha products were chemically analysed; (2) 'herbal' and tobacco
      shisha were burned in a waterpipe smoking machine and main and sidestream smoke
      analysed by standard methods and (3) the air quality of six waterpipe cafes was
      assessed by measurement of CO, particulate and nicotine vapour content. RESULTS:
      We found considerable variation in heavy metal content between the three products
      sampled, one being particularly high in lead, chromium, nickel and arsenic. A
      similar pattern emerged for polycyclic aromatic hydrocarbons. Smoke emission
      analyses indicated that toxic byproducts produced by the combustion of 'herbal'
      shisha were equivalent or greater than those produced by tobacco shisha. The
      results of our air quality assessment demonstrated that mean PM2.5 levels and CO
      content were significantly higher in waterpipe establishments compared to a
      casino where cigarette smoking was permitted. Nicotine vapour was detected in one
      of the waterpipe cafes. CONCLUSIONS: 'Herbal' shisha products tested contained
      toxic trace metals and PAHs levels equivalent to, or in excess of, that found in
      cigarettes. Their mainstream and sidestream smoke emissions contained carcinogens
      equivalent to, or in excess of, those of tobacco products. The content of the air
      in the waterpipe cafes tested was potentially hazardous. These data, in
      aggregate, suggest that smoking 'herbal' shisha may well be dangerous to health.

PMID- 24128427
TI  - What are the sales practices of internet cigar vendors in China?
AB  - OBJECTIVE: To estimate the number of websites selling cigars in China and to
      examine their sales and marketing practices. METHODS: Comprehensive searches were
      conducted using three keyword terms and two popular internet search engines. A
      total of 6000 sites were examined. Two raters examined the content of each site
      using a standardised coding instrument to assess geographic location, presence of
      warnings, products sold, and promotional strategies. RESULTS: We identified 106
      internet cigar vendors, which were located in 16 cities, with most of them being
      located in developed cities (eg, Shanghai, Guangzhou, Hong Kong). Only 6.6% of
      internet cigar vendors featured health warnings, and 14.2% featured minimum age
      of sale warnings. More than 80% of sites sold large cigars, 34.9% sold small or
      mini cigars, 42.5% sold cigarettes, 28.3% sold tobacco leaves, and 73.6% sold
      cigar accessories. Third-party online payment was the most frequently accepted
      payment method. Scanned images of cigars or cigar boxes (92.5%), reduced prices
      (84.0%), and diffusion of cigar-related information (67.9%) were the most
      frequently used promotional strategies.+ CONCLUSIONS: Internet cigar vendors
      undermine tobacco control policies and pose many challenges for tobacco control
      advocates in China. New legislation and enforcement should address these issues.

PMID- 24128429
TI  - Controversies in endocrinology: On the need for universal thyroid screening in
      pregnant women.
AB  - There is a well-known controversy among scientific societies regarding the
      recommendation to screen for thyroid dysfunction (TD) during pregnancy. Although
      several studies have shown an association between maternal subclinical
      hypothyroidism and/or hypothyroxinemia with obstetric problems and/or
      neurocognitive impairment in the offspring, there is only limited evidence on the
      possible positive effects of thyroxine (T4) treatment in such cases. Despite the
      scarcity of this evidence, there is a widespread agreement among clinicians on
      the need for treatment of clinical hypothyroidism during pregnancy and the risks
      that could arise due to therapeutic abstention. As maternal TD is a quite
      prevalent condition, easily diagnosed and for which an effective and safe
      treatment is available, some scientific societies have proposed to assess thyroid
      function during the first trimester of pregnancy and ideally before week 10 of
      gestational age. Given the physiologic changes of thyroid function during
      pregnancy, hormone assessment should be performed using trimester-specific
      reference values ideally based on locally generated data as geographic variations
      have been detected. Screening of TD should be based on an initial determination
      of TSH performed early during the first trimester and only if abnormal should it
      be followed by either a free or total T4 measurement. Furthermore, adequate
      iodine supplementation during pregnancy is critical and if feasible it should be
      initiated before the woman attempts to conceive. 

PMID- 24128430
TI  - The therapeutic outcome to intravenous steroid therapy for active Graves'
      orbitopathy is influenced by the time of response but not polymorphisms of the
      glucocorticoid receptor.
AB  - BACKGROUND: Glucocorticoids are the mainstay of immunosuppression for active
      moderate-severe Graves' orbitopathy (GO). AIM: To analyze the response to therapy
      and the contribution of glucocorticoid receptor (GR) gene polymorphisms to the
      therapeutic outcome of intravenous glucocorticoids (IVGC) in active moderate
      severe GO. METHODS: we have studied 58 patients treated with 7.5 g i.v.
      methylprednisolone (cumulative dose). ophthalmological assessment was performed
      at baseline and at 6-8, 12-16, and 24-30 weeks after the first infusion. Three GR
      gene polymorphisms, ER22/23EK, N363S, and BCL1, which have been associated to
      variable sensitivity to steroids, were studied in 43/58 patients. The therapeutic
      outcomes defined as: i) reduction of the clinical activity score (CAS) >=2 points
      or ii) reduction of proptosis >=2 mm or iii) improvement of diplopia according to
      the Gorman score were also studied in relation to treatment schedule, age,
      gender, duration of thyroid or GO, smoking habits, and serum TSH-receptor
      autoantibodies levels. RESULTS: In total, 70% of patients responded and had GO
      inactivation (CAS <4) as early as 6-8 weeks. At 12-16 weeks, the proportion of
      patients who became inactive increased by another 10% up to a total of 80%.
      ER22/23EK and N363S polymorphisms were present only in about 7%, while the Bcl1
      variant was present in 30% of patients; no significant association of any of the
      GR polymorphisms with either the therapeutic response or the occurrence of side
      effects was observed. CONCLUSIONS: Most patients with active GO respond to IVGC
      as early as 6-8 weeks of therapy and the analyzed GR polymorphisms do not
      influence the therapeutic effect of steroids. Questions arise about the need of
      continuing therapy up to 12 weeks in nonresponders. We suggest that these
      patients may be switched to other treatments alone or in combination with
      steroids.

PMID- 24128431
TI  - The relationship between circulating estradiol and thyroid autoimmunity in males.
AB  - INTRODUCTION: Although autoimmune thyroid disease is less common in males, it is
      unclear whether estrogen contributes to the difference in susceptibility among
      males. OBJECTIVE: To examine whether circulating estradiol (E2) is related to
      thyroid autoimmunity in males. PATIENTS AND METHODS: One-thousand two-hundred and
      sixty-three males aged 15-94 years were studied. Serum levels of E2, TSH receptor
      antibody (TRAb), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody
      (TgAb), free thyroxine (FT4), and TSH were measured by ELISA. RESULTS:
      Circulating E2 varied widely in males, ranging 18.4-403.7 pmol/l with a mean
      value of 136.2+/-51.7 pmol/l. E2 increased with age (r=0.18, P<0.001). No
      relationship between E2 and BMI was found. When comparing the difference in E2
      according to the test results of TRAb, TPOAb, and TgAb, it was found that E2 was
      significantly higher in subjects with positive TRAb (TRAb positive, E2=170.3+/
      59.8 pmol/l; TRAb negative, E2=134.0+/-50.6 pmol/l; P<0.001). No difference in E2
      was demonstrated according to the results of TPOAb or TgAb. Logistic regression
      analysis showed that E2 was a determinant of positive TRAb, independent of age
      and BMI. There was no relationship between serum E2 and TSH or FT4. However, E2
      was negatively related to TSH (r=-0.45, P<0.01) in subjects whose TSH levels fell
      below the reference range (0.3-4.2 mIU/l). CONCLUSION: Higher circulating E2 is
      related to thyroid autoimmunity in males as reflected by positive TRAb.

PMID- 24128432
TI  - The prince and the pauper: which one is real? The problem of secondary mutation
      during mutagenesis in Streptococcus pyogenes.

PMID- 24128433
TI  - The value and validation of broad spectrum biosensors for diagnosis and
      biodefense.
AB  - Broad spectrum biosensors capable of identifying diverse organisms are
      transitioning from the realm of research into the clinic. These technologies
      simultaneously capture signals from a wide variety of biological entities using
      universal processes. Specific organisms are then identified through bioinformatic
      signature-matching processes. This is in contrast to currently accepted molecular
      diagnostic technologies, which utilize unique reagents and processes to detect
      each organism of interest. This paradigm shift greatly increases the breadth of
      molecular diagnostic tools with little increase in biochemical complexity,
      enabling simultaneous diagnostic, epidemiologic, and biothreat surveillance
      capabilities at the point of care. This, in turn, offers the promise of increased
      biosecurity and better antimicrobial stewardship. Efficient realization of these
      potential gains will require novel regulatory paradigms reflective of the
      generalized, information-based nature of these assays, allowing extension of
      empirical data obtained from readily available organisms to support broader
      reporting of rare, difficult to culture, or extremely hazardous organisms. 

PMID- 24128434
TI  - Russian and Soviet forensic psychiatry: troubled and troubling.
AB  - Russian forensic psychiatry is defined by its troubled and troubling relationship
      to an unstable state, a state that was not a continuous entity during the modern
      era. From the mid-nineteenth century, Russia as a nation-state struggled to
      reform, collapsed, re-constituted itself in a bloody civil war, metastasized into
      a violent "totalitarian" regime, reformed and stagnated under "mature socialism"
      and then embraced capitalism and "managed democracy" at the end of the twentieth
      century. These upheavals had indelible effects on policing and the administration
      of justice, and on psychiatry's relationship with them. In Russia, physicians
      specializing in medicine of the mind had to cope with rapid and radical changes
      of legal and institutional forms, and sometimes, of the state itself. Despite
      this challenging environment, psychiatrists showed themselves to be active
      professionals seeking to guide the transformations that inevitably touched their
      work. In the second half of the nineteenth century debates about the role of
      psychiatry in criminal justice took place against a backdrop of increasingly
      alarming terrorist activity, and call for revolution. While German influence,
      with its preference for hereditarianism, was strong, Russian psychiatry was
      inclined toward social and environmental explanations of crime. When revolution
      came in 1917, the new communist regime quickly institutionalized forensic
      psychiatry. In the aftermath of revolution, the institutionalization of forensic
      psychiatry "advanced" with each turn of the state's transformation, with profound
      consequences for practitioners' independence and ethical probity. The abuses of
      Soviet psychiatry under Stalin and more intensively after his death in the 1960s
      80s remain under-researched and key archives are still classified. The return to
      democracy since the late 1980s has seen mixed results for fresh attempts to
      reform both the justice system and forensic psychiatric practice.

PMID- 24128435
TI  - [Inclusion-body myositis].
AB  - Sporadic inclusion-body myositis (sIBM) presents in average at the sixth decade
      of life and affects three men for one woman. It is a non-lethal, slowly
      progressive but disabling disease. Except the striated muscles, no other organs
      (such as the interstitial lung) are involved. The phenotype of this myopathy is
      particular since it involves the axial muscles (camptocormia, swallowing
      dysfunction) and limb girdle (notably the quadriceps) but also the distal muscles
      (in particular the fingers' and wrists' flexors) in a bilateral but non
      symmetrical manner. The clinical presentation is then very suggestive of the
      diagnosis, which remains to be proven by a muscle biopsy. Histological features
      defining the diagnosis associate endomysial inflammatory infiltrates with
      frequent invaded fibres (the myositis) and amyloid deposits generally
      accompanying rimmed vacuoles (the inclusions). There is still today a debate to
      know if this disease is at its beginning a degenerative or an auto-immune
      condition. Nonetheless, usual immunosuppressive drugs (corticosteroids,
      azathioprine, methotrexate) or polyvalent immunoglobulines remain ineffective and
      even may worsen the handicap. Some controlled randomized trials will soon be
      launched for this condition, but for now, the best therapeutic approach to slow
      down the rapidity of progression of the disease is to maintain muscle exercise
      with the help of the physiotherapists. 

PMID- 24128436
TI  - Preparation of porous styrenics-based monolithic layers for thin layer
      chromatography coupled with matrix-assisted laser-desorption/ionization time-of
      flight mass spectrometric detection.
AB  - Monolithic 50 MUm thin poly(4-methylstyrene-co-chloromethylstyrene-co
      divinylbenzene) layers attached to 6.0 cm * 3.3 cm glass plates have been
      prepared, using a thermally initiated polymerization process. These layers had a
      well-defined porous structure with a globular morphology demonstrated with SEM
      images and exhibited superhydrophobic properties characterized with a water
      contact angle of 157 degrees . They were then used for thin-layer chromatography
      of peptides and proteins fluorescently labeled with fluorescamine. The spots of
      individual separated compounds were visualized using UV light, and their
      identities were confirmed with a matrix-assisted laser desorption/ionization time
      of flight mass spectrometry. The presence of chloromethylstyrene units in the
      polymer enabled hypercrosslinking via a Friedel-Crafts alkylation reaction, and
      led to monoliths with much larger surface areas, which were suitable for
      separations of small dye molecules.

PMID- 24128437
TI  - Ultrathin-yttrium phosphate-shelled polyacrylate-ferriferrous oxide magnetic
      microspheres for rapid and selective enrichment of phosphopeptides.
AB  - Rapid and selective enrichment of phosphopeptides from complex biological samples
      is essential and challenging in phosphorylated proteomics. We present the direct
      growth of the ultrathin YPO4 shell on the surface of polyacrylate capped
      secondary Fe3O4 microspheres (PA-Fe3O4@YPO4) for the rapid and selective trapping
      phosphopeptides from complex samples. The prepared PA-Fe3O4@YPO4 could be rapidly
      harvested in the presence of an applied magnetic field and easily re-dispersed in
      solutions after removing the external magnet. The ultrathin YPO4 shell on super
      hydrophilic PA-Fe3O4 has the advantages of fast adsorption/desorption dynamics
      and low non-specific adsorption, thus trapping of phosphopeptides from the
      tryptic digests mixture of beta-casein/BSA with molar ratio of 1/300 is achieved
      in 20s adsorption/desorption time. Two phosphopeptides can still be detected with
      a signal to noise ratio (S/N) over 3 when the amount of beta-casein was as low as
      8 fmol.

PMID- 24128438
TI  - Estrogen response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the
      coexistence of multiple estrogen-deprivation resistant mechanisms.
AB  - The acquisition of estrogen-deprivation resistance and estrogen receptor (ER)
      signal-independence in ER-positive breast cancer is one of the crucial steps in
      advancing the aggressiveness of breast cancer; however, this has not yet been
      elucidated in detail. To address this issue, we established several estrogen
      deprivation-resistant (EDR) breast cancer cell lines from our unique MCF-7 cells,
      which had been stably transfected with an ERE-GFP reporter plasmid. Three cell
      lines with high ER activity and another 3 cell lines with no ER activity were
      established from cell cloning by monitoring GFP expression in living cells. The
      former three ERE-GFP-positive EDR cell lines showed the overexpression of ER and
      high expression of several ER-target genes. Further analysis of intracellular
      signaling factors revealed a marked change in the phosphorylation status of
      ERalpha on Ser167 and Akt on Thr308 by similar mechanisms reported previously;
      however, we could not find any changes in MAP-kinase factors. Comprehensive
      phospho-proteomic analysis also indicated the possible contribution of the Akt
      pathway to the phosphorylation of ERalpha. On the other hand, constitutive
      activation of c-Jun N-terminal kinase (JNK) was observed in ERE-GFP-negative EDR
      cells, and the growth of these cells was inhibited by a JNK inhibitor. An IGF1R
      specific inhibitor diminished the phosphorylation of JNK, which suggested that a
      novel signaling pathway, IGF1R-JNK, may be important for the proliferation of ER
      independent MCF-7 cells. These results indicate that ER-positive breast cancer
      cells can acquire resistance by more than two mechanisms at a time, which
      suggests that multiple mechanisms may occur simultaneously. This finding also
      implies that breast cancers with different resistance mechanisms can
      concomitantly occur and mingle in an individual patient, and may be a cause of
      the recurrence of cancer. 

PMID- 24128439
TI  - DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response
      variation.
AB  - Factors contributing to the variability of serum 25-hydroxyvitamin D [25(OH)D] in
      response to a given dose of vitamin D supplementation are largely unknown. We
      examined whether DNA methylation levels of Cytochrome P450 (CYP) enzymes (CYP2R1,
      CYP24A1, CYP27A1, and CYP27B1) are potential biomarkers predicting vitamin D
      response variation. We randomized 446 white postmenopausal women to a calcium and
      vitamin D (1100IU/day) intervention for at least 12 months. From these subjects,
      18 with the highest 12-month increase in serum 25(OH)D were selected as
      "responders." Another 18 with the lowest 12-month increase in serum 25(OH)D were
      selected as "non-responders." DNA methylation levels between the groups were
      compared. To validate findings in the first study, association between DNA
      methylation levels and vitamin D response variation was studied in another 145
      extended independent white postmenopausal women. In the first study, compared to
      non-responders, responders had significantly lower baseline DNA methylation
      levels in the promoter region of CYP2R1 (8% in the responders vs. 30% in the non
      responders, P=0.004), and CYP24A1 (13% in the responders vs. 32% in the non
      responders, P=0.001). In the validation study, for CYP2R1, baseline DNA
      methylation levels at eight CpG sites were negatively associated with 12-month
      increases in serum 25(OH)D (P<0.05). For CYP24A1, baseline DNA methylation levels
      at two CpG sites were also negatively associated with vitamin D response
      variation (r=-0.151, P=0.011; r=-0.131, P=0.025). These negative associations
      were consistent with the first study's results. Our findings indicate that
      baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D
      response variation. This article is part of a Special Issue entitled '16th
      Vitamin D Workshop'. 

PMID- 24128441
TI  - Preliminary separation and purification of resveratrol from extract of peanut
      (Arachis hypogaea) sprouts by macroporous adsorption resins.
AB  - In the present study, the separation and purification characteristics of
      resveratrol from extract of peanut sprouts (PSE) on 11 macroporous adsorption
      resins were investigated. The results showed that ADS-5 offered better adsorption
      and desorption capacity for resveratrol than other tested resins. From the static
      experiments with ADS-5 resin, we found that the experimental data fitted best to
      the pseudo-second-order kinetics model and Langmuir isotherm model, and the
      adsorption was a spontaneous and endothermic process. The separation and
      purification parameters of resveratrol from PSE were optimised by dynamic
      adsorption/desorption experiments with the column packed with ADS-5 resin. Under
      the optimal conditions, after one run treatment with ADS-5 resin, the content of
      resveratrol in the product was increased 17.9-fold from 1.32% to 23.60%, with a
      recovery yield of 88.33%. The results demonstrated that ADS-5 resin was a
      promising basis for large-scale preliminary separation and purification of
      resveratrol from PSE. 

PMID- 24128440
TI  - Recent progress in synthetic and biological studies of GPI anchors and GPI
      anchored proteins.
AB  - Covalent attachment of glycosylphosphatidylinositols (GPIs) to the protein C
      terminus is one of the most common posttranslational modifications in eukaryotic
      cells. In addition to anchoring surface proteins to the cell membrane, GPIs also
      have many other important biological functions, determined by their unique
      structure and property. This account has reviewed the recent progress made in
      disclosing GPI and GPI-anchored protein biosynthesis, in the chemical and
      chemoenzymatic synthesis of GPIs and GPI-anchored proteins, and in understanding
      the conformation, organization, and distribution of GPIs in the lipid membrane. 

PMID- 24128442
TI  - Phytochemical and physical-chemical analysis of Polish willow (Salix spp.) honey:
      identification of the marker compounds.
AB  - The case study of Polish Salix spp. honey was compared with published data on
      willow honey from other regions. GC-FID/MS (after HS-SPME and ultrasonic solvent
      extraction) and targeted HPLC-DAD were applied. Phenolic content, FRAP/DPPH
      assays and the colour coordinates were determined spectrophotometrically. Beside
      ubiquitous linalool derivatives, borneol (up to 10.9%), bicyclic monoterpenes
      with pinane skeleton (pinocarvone up to 10.6%, myrtenal up to 4.8% and verbenone
      up to 3.4%) and trans-beta-damascenone (up to 13.0%) dominated in the headspace.
      The main compounds of the extractives were vomifoliol (up to 39.6%) and methyl
      syringate (up to 16.5%) along with not common 4-hydroxy-3-(1
      methylethyl)benzaldehyde (up to 11.1%). Abscisic acid (ABA) was found (up to 53.7
      mg/kg) with the isomeric ratio (Z,E)-ABA:(E,E)-ABA=1:2. The honey exhibited low
      antioxidant potential with pale yellow colour. The composition of Polish willow
      honey is similar to Mediterranean willow honeys with several relevant
      differences.

PMID- 24128443
TI  - Characterization of seed and skin polyphenolic extracts of two red grape
      cultivars grown in Croatia and their sensory perception in a wine model medium.
AB  - A study of proanthocyanidin and anthocyanin composition and concentrations in
      seed and skin extracts of two Croatian native red grape cultivars (Plavac mali
      and Babic) by HPLC-UV-Fluo/MS analysis was conducted in this work. A sensory
      analysis of extracts astringency and bitterness intensity was also performed. In
      the seeds, Babic showed generally higher concentrations of proanthocyanidins,
      while in the skins, Plavac mali showed higher concentrations of proanthocyanidins
      and anthocyanins. Babic proanthocyanidin seed fractions, greater in polymer size
      and percentage of galloylation, were perceived to be significantly more
      astringent. Babic proanthocyanidin skin fractions, greater in polymer size and
      lower in percentage of galloylation and prodelphinidins, were perceived to be
      significantly bitterer, but only in polymeric fractions. A positive correlation
      was found between the degree of polymerization, the percentage of galloylation
      and astringency intensity in the seeds. A negative correlation was found between
      the percentage of prodelphinidins and bitterness intensity in the skins. 

PMID- 24128444
TI  - Effect of storage time and temperature on the physicochemical and sensory
      characteristics of commercial apricot jam.
AB  - Storage conditions are important factors for jam quality. The objective of this
      study was to monitor the physicochemical stability and sensorial profile of
      apricot jam during storage for 60 days at 5  degrees C, 25  degrees C and 37 
      degrees C. For that purpose, special attention was paid to total soluble solids
      (TSS), titratable acidity (TA), colour, free amino acids (FAA), total sugars (TS)
      and hydroxymethylfurfural (HMF). The decreasing parameter for jam at the end of
      storage under 5  degrees C, 25  degrees C and 37  degrees C, respectively, were
      16.81%, 34.30% and 56.01% for FAA, and 5.52%, 9.02% and 7.46% for TS; likewise,
      the increasing were 19.81%, 22.94% and 25.07% for TA, 3.15%, 4.08% and 4.47% for
      TSS, 15.96%, 112.76% and 150% for HMF. Jam stability was better at 5  degrees C
      than 25  degrees C and 37  degrees C. The interaction time-temperature factor had
      significant effects on pH, TS, FAA and HMF, unlike TA, TSS and sensorial profile.

PMID- 24128445
TI  - Preparation and evaluation of ionic liquid-calixarene solid-phase microextraction
      fibres for the determination of triazines in fruit and vegetable samples.
AB  - A new ionic liquid (IL)-calixarene coated solid-phase microextraction (SPME)
      fibre has been synthesized on the surface of quartz fibre by the sol-gel method.
      The coated fibre has been coupled with gas chromatography-flame ionisation
      detector (GC-FID) for the determination of triazines in fruit and vegetable
      samples. The operation parameters including sample volume, extraction time,
      extraction temperature, desorption time, and sample pH have been investigated and
      optimised. Under the optimum conditions, the limits of detection of atrazine,
      simazine, ametryn, and cyanazine based on three times of standard deviations of
      blank by seven replications are 3.3, 4.4, 8.8, and 13.0 MUg kg(-1), respectively.
      The intra-day and inter-day relative standard deviations are less than 7.2% and
      9.9%. The proposed method has been successfully applied to the determination of
      the four triazines in fruit and vegetable samples and the accuracy is assessed
      through recovery experiments.

PMID- 24128446
TI  - ACE-inhibitory activity of enzymatic protein hydrolysates from lupin and other
      legumes.
AB  - The objective of this investigation was to compare the angiotensin converting
      enzyme (ACE)-inhibitory activity of the hydrolysates obtained by pepsin digestion
      of proteins of some legumes, such as chickpea, common bean, lentil, lupin, pea,
      and soybean, by using the same experimental procedure. The ACE-inhibitory
      activity was measured by using the tripeptide hippuryl-histidyl-leucine (HHL), as
      model peptide, and HPLC-DAD, as analytical method. The peptide mixtures of all
      legumes were active, with soybean and lupin the most efficient, with IC50 values
      of 224 and 226 MUg/ml, respectively. Considering the promising results obtained
      with lupin, and aiming to identify the protein(s) that release(s) the peptides
      responsible for the activity, the peptides obtained from the pepsin digestion of
      some industrial lupin protein isolates and purified protein fractions were
      tested. The most active mixture, showing an IC50 value of 138 MUg/ml, was
      obtained hydrolysing a mixture of lupin alpha+beta conglutin.

PMID- 24128447
TI  - Determination of eight triazine herbicide residues in cereal and vegetable by
      micellar electrokinetic capillary chromatography with on-line sweeping.
AB  - A new method was developed for the determination of eight triazine herbicide
      residues in cereal and vegetable samples by on-line sweeping technique in
      micellar electrokinetic capillary chromatography (MEKC). Some factors affecting
      analyte enrichment and separation efficiency were examined. The optimum buffer
      was composed of 25 mM borate, 15 mM phosphate, 40 mM sodium dodecylsulfate (SDS)
      and 3% (v/v) of 1-propanol at pH 6.5. The separation voltage was 20 kV and the
      sample was injected at 0.5 psi for 240 s. The detection wavelength was set at 220
      nm with the capillary temperature being at 25  degrees C. Under the optimized
      conditions, the enrichment factors were achieved from 479 to 610. The limits of
      detection (LODs, S/N = 3) ranged from 0.02 to 0.04 ng/g and the limits of
      quantification (LOQs) of eight triazine herbicides were all 0.1 ng/g. The average
      recoveries of spiked samples were 82.8-96.8%. This method has been successfully
      applied to the determination of the triazine herbicide residues in cereal and
      vegetable samples.

PMID- 24128448
TI  - A new dual plasmid calibrator for the quantification of the construct specific GM
      canola Oxy-235 with duplex real-time PCR.
AB  - To overcome the difficulties of obtaining the Certified Reference Material (CRM)
      and according to the key documents of the European Union Reference Laboratory (EU
      RL), a new standard reference molecule containing the construct specific of the
      canola event Oxy-235 (3'-junction Nitrilase/Tnos) and the canola endogenous
      reference gene (acety-CoA-carboxylase) was constructed and used for duplex real
      time quantitative analysis. The limits of detection (LOD) were less than 5
      Haploid Genome Copy (HGC) and the limits of quantification (LOQ) were about 10
      HGC. Furthermore, mixed GM and non-GM canola samples were analysed with duplex
      QRT-PCR to evaluate the performance criteria as required for validation
      procedures in the EU-RL, namely, the precision and the accuracy. The accuracy
      expressed as bias ranged from 2% to 10% and the precision (repeatability and
      reproducibility) expressed as the RSDr and RSDR was from 2.2 to 5.12 and 2.15 to
      5.46 respectively. All these indicated that the developed construct specific
      method and the reference molecule are suitable for the identification and the
      quantification of the canola event Oxy-235. 

PMID- 24128449
TI  - Assessment of free radicals scavenging activity of seven natural pigments and
      protective effects in AAPH-challenged chicken erythrocytes.
AB  - The purpose of this study was to compare the antioxidant capacities of seven
      natural pigments including the fat-soluble pigments curcumin, lycopene, lutein
      and beta-carotene and water-soluble pigments--betalain, capsanthin and cyanidin-3
      rutinoside relative to a commonly-used synthetic food antioxidant BHA. The
      antioxidant capacities of seven pigments and BHA were evaluated based on their
      ability to quench several free radicals, including DPPH, ABTS, O2(.-), H2O2 as
      well as using FRAP assay. Specifically, curcumin and cyanidin-3-rutinoside, which
      showed the highest antioxidant capacities, were further investigated using a
      chicken erythrocyte model. After separating pretreatments of the two pigments,
      AAPH was added to the erythrocyte-pigment medium to induce oxidative stress. Then
      the attenuation effects of the two pigments on AAPH-induced oxidative damage in
      chicken erythrocytes were assessed. It was found that both curcumin and cyanidin
      3-rutinoside significantly attenuated apoptosis and hemolysis, decreased MDA
      content, and increased T-SOD activity in a time- and dose- dependent manner.

PMID- 24128450
TI  - Anti-diabetic and antihypertensive activities of two flaxseed protein hydrolysate
      fractions revealed following their simultaneous separation by electrodialysis
      with ultrafiltration membranes.
AB  - Flaxseed protein hydrolysate has been fractionated by electrodialysis with two
      ultrafiltration membranes (20 and 50 kDa) stacked in the system for the recovery
      of two specific cationic peptide fractions (KCl-F1 and KCl-F2). After 360 min of
      treatment, peptide migration increased as a function of time in KCl compartments.
      Moreover, the use of two different ultrafiltration membrane allowed concentration
      of the 300-400 and 400-500 Da molecular weight range peptides in the KCl-F1 and
      KCl-F2 fractions, respectively, compared to the initial hydrolysate. After mass
      spectrometry analysis, higher amounts of low molecular weight peptides were
      recovered in the KCl-F2 compartment while relatively higher molecular weight
      peptides were more detected in the KCl-F1 compartment. Amino acid analysis showed
      that His, Lys and Arg were especially concentrated in the KCl compartments.
      Finally, glucose-transport assay demonstrated that the KCl-F2 fraction increased
      glucose uptake while oral administration of KCl-F1 and final FPH decreased
      systolic blood pressure.

PMID- 24128451
TI  - Quantification of glucosinolates, anthocyanins, free amino acids, and vitamin C
      in inbred lines of cabbage (Brassica oleracea L.).
AB  - We profiled and quantified glucosinolates (GSLs), anthocyanins, free amino acids,
      and vitamin C metabolites in forty-five lines of green and red cabbages. Analysis
      of these distinct cabbages revealed the presence of 11 GSLs, 13 anthocyanins, 22
      free amino acids, and vitamin C. GSL contents were varied amongst the different
      lines of cabbage. The total GSL content was mean 10.6 MUmol/g DW, and sinigrin
      was the predominant GSL accounted mean 4.0 MUmol/g DW (37.7% of the total)
      followed by glucoraphanin (1.9) and glucobrassicin (2.4). Amongst the 13
      anthocyanins, cyanidin 3-(sinapoyl) diglucoside-5-glucoside levels were the
      highest. The amounts of total free amino acids in green cabbage lines ranged
      365.9 mg/100g fresh weight (FW) to 1089.1mg/100g FW. Vitamin C levels were much
      higher in red cabbage line (129.9 mg/100g FW). Thus, the amounts of GSLs,
      anthocyanins, free amino acids, and vitamin C varied widely, and the variations
      in these compounds between the lines of cabbage were significant.

PMID- 24128452
TI  - Effect of MeJA treatment on polyamine, energy status and anthracnose rot of
      loquat fruit.
AB  - The effect of methyl jasmonate (MeJA) on changes in polyamines content and energy
      status and their relation to disease resistance was investigated. Freshly
      harvested loquat fruit were treated with 10 MUmol l(-1) MeJA and wound inoculated
      with Colletotrichum acutatum spore suspension (1.0 * 10(5) spores ml(-1)) after
      24h, and then stored at 20  degrees C for 6 days. MeJA treatment significantly
      reduced decay incidence. MeJA treated fruit manifested higher contents of
      polyamines (putrescine, spermidine and spermine) compared with the control fruit,
      during storage. MeJA treatment also maintained higher levels of adenosine
      triphosphate, and suppressed an increase in adenosine monophosphate content in
      loquat fruit. These results suggest that MeJA treatment may inhibit anthracnose
      rot by increasing polyamine content and maintaining the energy status.

PMID- 24128453
TI  - Serum albumin forms a lactoferrin-like soluble iron-binding complex in presence
      of hydrogen carbonate ions.
AB  - The iron-lactoferrin complex is a common food ingredient because of its iron
      solubilizing capability in the presence of hydrogen carbonate ions. However, it
      is unclear whether the formation of a stable iron-binding complex is limited to
      lactoferrin. In this study, we investigated the effects of bovine serum albumin
      (BSA) on iron solubility and iron-catalyzed lipid oxidation in the presence of
      hydrogen carbonate ions. BSA could solubilize >100-fold molar equivalents of iron
      at neutral pH, exceeding the specific metal-binding property of BSA. This iron
      solubilizing capability of BSA was impaired by thermally denaturing BSA at >= 70 
      degrees C for 10 min at pH 8.5. The resulting iron-BSA complex inhibited iron
      catalyzed oxidation of soybean oil in a water-in-oil emulsion measured using the
      Rancimat test. Our study is the first to show that BSA, like lactoferrin, forms a
      soluble iron-binding complex in the presence of hydrogen carbonate ions.

PMID- 24128454
TI  - Antioxidant activity and bioactive compounds of lettuce improved by espresso
      coffee residues.
AB  - The antioxidant activity and individual bioactive compounds of lettuce,
      cultivated with 2.5-30% (v/v) of fresh or composted espresso spent coffee
      grounds, were assessed. A progressive enhancement of lettuce's antioxidant
      capacity, evaluated by radical scavenging effect and reducing power, was
      exhibited with the increment of fresh spent coffee amounts, while this pattern
      was not so clear with composted treatments. Total reducing capacity also
      improved, particularly for low spent coffee concentrations. Additionally, very
      significant positive correlations were observed for all carotenoids in plants
      from fresh spent coffee treatments, particularly for violaxanthin, evaluated by
      HPLC. Furthermore, chlorophyll a was a good discriminating factor between control
      group and all spent coffee treated samples, while vitamin E was not significantly
      affected. Espresso spent coffee grounds are a recognised and valuable source of
      bioactive compounds, proving herein, for the first time, to potentiate the
      antioxidant pool and quality of the vegetables produced. 

PMID- 24128455
TI  - Anti-staling effects of beta-glucan and barley flour in wheat flour chapatti.
AB  - Chapatti making behaviour of wheat flour containing barley flour (28%, 56% and
      84%) or beta-glucan (1.5%, 3.0% and 4.5%) and their effect on staling of chapatti
      was studied. The dough water absorption increased significantly up to 76.7% and
      78.3% upon incorporation of barley flour and beta-glucan, respectively. Bake loss
      significantly increased (up to 20%) upon incorporation of barley flour but was
      not significantly affected by beta-glucan. The peak (PV) and final viscosity (FV)
      significantly increased upon incorporation of barley flour (up to 105% and 65%),
      whereas incorporating beta-glucan decreased the PV and FV by 20.3% and 20.6%,
      respectively. The stored chapatties exhibited higher pasting viscosities compared
      to the fresh chapatties. Incorporation of barley flour exhibited a gradual
      increase in the enthalpy of gelatinisation (DeltaHgel), similarly beta-glucan at
      1.5% increased the DeltaHgel. Retrogradation was lowered by 23.7%, 41.5% and
      63.5% by barley flour and by 19.9%, 27.4% and 44.8% by beta-glucan. 

PMID- 24128456
TI  - Simultaneous separation and determination of five organic acids in beverages and
      fruits by capillary electrophoresis using diamino moiety functionalized silica
      nanoparticles as pseudostationary phase.
AB  - A kind of novel diamino moiety functionalized silica nanoparticles with the
      diameter of ~110 nm was successfully prepared and characterised by transmission
      electron microscope (TEM) and elemental analysis. Capillary electrophoresis (CE)
      with this kind of nanoparticles as pseudostationary phase was developed for the
      simultaneous analysis of five organic acids in beverage and fruit samples. The
      effects of pH, buffer concentration, and nanoparticles concentration on
      separation were carefully investigated. Five organic acids were baseline
      separated in 5 min under optimum experimental conditions. The precisions for five
      replicate separations of a standard mixture solution were 2.71-6.13% for peak
      area and 1.22-1.93% for migration time respectively. The detection limits were
      7.5, 0.15, 0.23, 0.33 and 10.0mg/L for citric acid, salicylic acid, benzoic acid,
      sorbic acid and ascorbic acid, respectively. The developed method was applied to
      the simultaneous analysis of five analytes in beverage and fruit samples and
      certified reference materials with satisfactory results.

PMID- 24128457
TI  - Strategies to improve the solubility and stability of stilbene antioxidants: a
      comparative study between cyclodextrins and bile acids.
AB  - Aiming at the development of an active food packaging, the goal of this study was
      to increase stilbenes (resveratrol (RV), pterostilbene (PT) and pinosylvin (PS))
      aqueous solubility and stability using hydropropyl-cyclodextrins (HP-CDs) and
      bile salts. To evaluate stilbene concentration, an HPLC-DAD method was validated.
      Stilbene solubility was improved by the formation of inclusion complexes and
      micellar systems with higher solubility values obtained for the inclusion
      complexes with cyclodextrins. Inclusion complexes revealed a 1:1 stoichiometry
      for RV and PT and a 1:2 for PS. Solid state characterisation was carried out
      using X-ray diffraction, Fourier transform infrared spectroscopy and differential
      scanning calorimetry. (1)H NMR studies were also performed to characterise the
      prepared complexes. Photostability studies revealed that CDs were able to
      increase stilbene photostability at 4  degrees C. This work showed that stable
      stilbene solutions can be achieved using hydroxypropyl-CDs, contributing for
      their incorporation in several materials for the food and pharmaceutical
      industries.

PMID- 24128458
TI  - Evaluation of aroma differences between high-salt liquid-state fermentation and
      low-salt solid-state fermentation soy sauces from China.
AB  - Two types of Chinese soy sauce, high-salt liquid-state fermentation soy sauce
      (HLFSS) and low-salt solid-state fermentation soy sauce (LSFSS), were used to
      investigate their differences in aroma profile by headspace solid-phase
      microextraction (HS-SPME) and gas chromatography-olfactometry/mass spectrometry
      (GC-O/MS). Results from descriptive sensory analysis showed that the alcoholic,
      cooked potato-like and caramel-like attributes were significantly higher in
      HLFSS, while LSFSS exhibited significantly higher sour and burnt attributes. In
      addition, aroma extract dilution analysis (AEDA) revealed 37 and 33 odour-active
      regions for HLFSS and LSFSS, respectively. Ethanol, 3-methyl-1-butanol,
      phenylacetaldehyde, 4-ethyl-2-methoxyphenol, 2-methoxy-4-vinylphenol and 3
      (methylthio)propanal detected in HLFSS showed the highest flavour dilution (FD)
      factors, while 3-methylbutanal, phenylacetaldehyde and ethyl propanoate possessed
      the highest FD factors in LSFSS. Therefore, the traditional Chinese soy sauce
      HLFSS contained more complex volatiles and exhibited a richer aromatic profile
      compared with LSFSS. 

PMID- 24128459
TI  - Characteristics of lipid and fatty acid of marine gastropod Turbo cornutus: high
      levels of arachidonic and n-3 docosapentaenoic acid.
AB  - Phosphatidylethanolamine and phosphatidylcholine were major components in the
      foot lipids of the turban shell Turbo cornutus, while triacylglycerol was the
      major one in its viscera, which demonstrate the high level of lipid in all
      specimens. The major polyunsaturated fatty acids (PUFA) in the major lipid
      classes of T. cornutus were 20:4n-6 (arachidonic acid; ARA), 20:5n-3
      (ecosapentaenoic acid; EPA), 22:4n-6, and 22:5n-3 (docosapentaenoic acid; n-3
      DPA), with very low levels of 22:6n-3 (docosahexaenoic acid; DHA). The unusual
      high levels of ARA, 22:4n-6, and n-3 DPA found in both the triacylglycerols and
      phospholipids of all specimens suggest the influence of dietary algae on its
      tissue lipids. In the polar lipids, the total PUFA content was consistently high,
      with n-6 PUFA compensating for the fluctuation in the total n-3 PUFA levels. T.
      cornutus concentrated high levels of ARA in the visceral lipids from the dietary
      algae whose lipid content were very low. The viscera may effectively serve as a
      source of ARA for infant formulas. High levels of ARA, EPA, and n-3 DPA in the
      phospholipids of T. cornutus were observed. T. cornutus is a healthful marine
      food containing high levels of n-3 DPA. 

PMID- 24128460
TI  - The fortification of tea with sweeteners and milk and its effect on in vitro
      antioxidant potential of tea product and glutathione levels in an animal model.
AB  - Several studies have demonstrated that tea flavonoids protect cells and tissues
      against free radicals which have been implicated in the etiology of oxidative
      stress-related disease disorders. However, black tea is commonly consumed with
      additives that could otherwise affect the bioavailability of the active tea
      molecules. In this study, the biochemical parameters of Kenyan teas were
      determined and the effect of added milk and sweeteners on the antioxidant
      activity of Kenyan teas was investigated. The effect of tea antioxidants on
      glutathione (GSH) was also evaluated in vivo in a time series study using Swiss
      mice. Green teas had the highest levels of total polyphenols, total and
      individual catechins, while black teas had high levels of total thearubigins,
      total theaflavins and theaflavin fractions. The antioxidant activity was high in
      green teas though some of the black teas were as efficacious as the green teas.
      The addition of milk, sugar and honey significantly (p<0.05) decreased the
      antioxidant activity of tea in a concentration-dependent manner. Addition of the
      sweetener, stevia (Stevia rebaudiana Bertoni), showed no significant (p>0.05)
      influence on the antioxidant activity of tea and therefore can be recommended as
      a preferred sweetener for tea. Significantly (p<0.001) higher levels of GSH were
      observed in plasma than in other tissues. GSH levels were generally highest 2h
      after tea consumption, which indicates the need to repeatedly take tea every 2h
      to maximise its potential health benefits. 

PMID- 24128461
TI  - Jack bean urease inhibition by crude juices of Allium and Brassica plants.
      Determination of thiosulfinates.
AB  - The aim of this study was the elucidation of the inhibitory influence of Allium
      (garlic, onion, leek) and Brassica (cabbage, Brussels sprouts) plants juices, on
      jack bean urease activity. Concentrations of thiosulfinates, the compounds
      responsible for the inhibition, were determined in studied materials. The
      kinetics and mechanism of the inhibitions were investigated. Biphasic, time
      dependent courses of the inhibition reactions were observed for all tested Allium
      and Brussels sprouts from Brassica. The cabbage material caused the monophasic
      course of the inhibition. In the presence of dithiothreitol, a total reactivation
      of the inhibited urease proceeded for the tested plants except for the onion. The
      onion juice modified urease, regained only half of the initial activity. The
      irreversible contribution was related to the presence of 1-propanethial-S-oxide,
      cepaenes and zwiebelanes formed in the onion juice. It was found that the thermal
      processing of the plant juices, results in the decrease of thiosulfinates
      concentration, as well as the efficiency of urease inhibition. 

PMID- 24128462
TI  - Novel solid phase extraction method for the analysis of 5-nitroimidazoles and
      metabolites in milk samples by capillary electrophoresis.
AB  - A new sample treatment has been developed for the extraction of 5-nitroimidazole
      (5-NDZ) drugs in milk samples previous to their determination by micellar
      electrokinetic chromatography (MEKC). Fat removing and protein precipitation were
      simultaneously carried out by the addition of trichloroacetic acid (TCA) and
      subsequent centrifugation. Clean-up and off-line concentration were achieved by a
      novel solid-phase extraction (SPE) method employing mixed cation exchange (MCX)
      cartridges, obtaining an off-line concentration factor of 18. Analyses were
      performed in less than 18 min employing 20mM phosphate buffer (pH 6.5) and 150 mM
      SDS as background electrolyte (BGE). During the separation procedure a
      temperature of 20  degrees C and a voltage of 25 kV (normal mode) were applied.
      Due to sweeping effects, an on-line concentration was achieved for all the
      studied compounds and detection limits lower than 1.8 MUg L(-1) were obtained.
      This method has been successfully applied to milk samples of different origins,
      including raw ewe milk.

PMID- 24128463
TI  - Effect of vacuum roasting on acrylamide formation and reduction in coffee beans.
AB  - Coffea arabica beans were roasted in an oven at 200  degrees C for increasing
      lengths of time under vacuum (i.e. 0.15 kPa). The samples were then analysed for
      colour, weight loss, acrylamide concentration and sensory properties. Data were
      compared with those obtained from coffee roasted at atmospheric pressure (i.e.
      conventional roasting), as well as at atmospheric pressure for 10 min followed by
      vacuum treatment (0.15 kPa; i.e. conventional-vacuum roasting). To compare the
      different treatments, weight loss, colour and acrylamide changes were expressed
      as a function of the thermal effect received by the coffee beans during the
      different roasting processes. Vacuum-processed coffee with medium roast degree
      had approximately 50% less acrylamide than its conventionally roasted
      counterpart. It was inferred that the low pressure generated inside the oven
      during the vacuum process exerted a stripping effect preventing acrylamide from
      being accumulated. Vacuum-processed coffee showed similar colour and sensory
      properties to conventionally roasted coffee.

PMID- 24128464
TI  - Preparation and antioxidant potential of maillard reaction products from (MRPs)
      chitooligomer.
AB  - Maillard reaction products (MRPs) were prepared from a chitooligomer solution by
      heating at 80  degrees C for different times. A time-dependent increase in UV
      absorbance, browning, and fluorescence was observed upon heating, indicating
      formation of MRPs with heating of the chitooligomer solution. The formation was
      also evidenced by Fourier transform infrared and molecular weight distribution,
      using gel permeation chromatography. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and
      2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS(+))-scavenging
      activities, and MRPs, reducing power increased significantly (p<0.05) with an
      increase in heating time of the chitooligomer solution. MRPs240 was formed after
      240 min of heating and showed an inhibitory concentration required for 50%
      scavenging (IC50) value of 118 MUg/ml (against DPPH), 266 MUM ascorbic acid
      equivalent (AE)/mg MRPs240 (against ABTS(+)), and 521 MUM AE/mg MRPs240 (against
      reducing power). MRPs240 exhibited lipid peroxidation inhibition activity in a
      linoleic acid emulsion, and the malondialdehyde concentration decreased from 29.6
      to 8.4 MUM. In addition, MRPs showed protection ability against the oxidative
      stress induced by H2O2 in Chang liver cells.

PMID- 24128465
TI  - Albarino wine aroma enhancement through the use of a recombinant
      polygalacturonase from Kluyveromyces marxianus.
AB  - The possible biotechnological application of a recombinant endopolygalacturonase
      of Kluyveromyces marxianus (KMPG) for the aroma enhancement of Albarino wine was
      studied. The addition of this enzyme to the must gives rise to a significant
      increase of the total compounds responsible for the aroma as opposed to the
      effect when using a commercial pectic enzyme. This increase also results in a
      significant rise of the odoriferous aglycones which are direct determinants of
      the aroma. Wines made by using the KMPG enzyme are characterised by a greater
      richness and diversity with regard to the number of aromatic compounds present,
      clearly differing from those obtained with a commercial pectic preparation. Based
      on compounds with odour activity values (OAV)>1, the wines obtained with the
      enzyme KMPG are richer in citric, balsamic, spicy and above all floral (violet
      and rose) aromas than untreated wines or wines supplemented with a commercial
      enzyme. 

PMID- 24128466
TI  - Identification of saffron aroma compound beta-isophorone (3,5,5-trimethyl-3
      cyclohexen-1-one) in some V. vinifera grape varieties.
AB  - Carotenoid-derived aroma compounds play an important role in the composition of
      aroma and grapes, and consequently of wine. The volatile composition of forty
      five grape varieties harvested in 2011 and 2012 was investigated by solid phase
      extraction of samples and gas chromatography-mass spectrometry (GC-MS) analysis.
      In grape extracts of cultivars Barbera, Refosco dal Peducolo Rosso, Ribolla
      gialla and Rossese, the C9-norisoprenoid compound beta-isophorone (3,5,5
      trimethyl-3-cyclohexen-1-one) was found and quantified. This carotenoid-derived
      compound is characterised by a saffron aroma and is here reported in grape for
      the first time. 

PMID- 24128467
TI  - Brewery waste as a potential source of phenolic compounds: optimisation of the
      extraction process and evaluation of antioxidant and antimicrobial activities.
AB  - This paper reports the development of an extraction process that allows selective
      recovery of polyphenols from a brewery waste stream. The antioxidant activity of
      this extract (EC50 = 0.23-0.3g/L) was very high, similar to that of butylated
      hydroxyanisole (BHA) and higher than that of other synthetic antioxidants such as
      butylated hydroxytoluene (BHT). Crude extracts exhibited a high level of
      antimicrobial activity against Gram-positive and Gram-negative bacteria, when
      applied at concentrations of 1% and 3% (w/v). The antioxidant and antimicrobial
      activities can probably be attributed to the major phenolic compounds, such as
      protocatechuic, caffeic, p-coumaric and ferulic acids and catechin. With this
      procedure, the waste polyphenols could be used as cheap source of natural
      compounds, with potential applications in the food and health sectors.
      Substitution of synthetic additives with safe and effective natural additives may
      be of further benefit to the food industry.

PMID- 24128468
TI  - AMP-activated protein kinase mediates insulin-like and lipo-mobilising effects of
      beta-glucan-rich polysaccharides isolated from Pleurotus sajor-caju (Fr.), Singer
      mushroom, in 3T3-L1 cells.
AB  - Mushrooms have been used to treat various diseases for thousands of years. In the
      present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis,
      lipolysis and oxidative stress in 3T3-L1 cells were investigated. The beta-glucan
      rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis
      but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells.
      This extract caused an increase in the expression of 5'-AMP-activated protein
      kinase subunit gamma-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit gamma
      3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the
      expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes,
      leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have
      contributed to the lipolytic and insulin-like activities observed in this study.
      These findings suggest that GE is a novel AMPK activator that may be valuable in
      the formulation of nutraceuticals and functional food for the prevention and
      treatment of diabetes mellitus. 

PMID- 24128469
TI  - Phytonutrients for controlling starch digestion: evaluation of grape skin
      extract.
AB  - The objective of this work was to evaluate the structure-function relationship
      between grape skin extract and human alpha-amylase. The grape skin extract was
      characterised as resveratrol-3-O-glucoside by RP-HPLC-ESI-MS, which showed strong
      inhibition towards alpha-amylase and the IC50 value was 1.35 mg/ml. The kinetic
      results demonstrated grape skin extract obeyed the non-competitive mode against
      amylase. Fluorescence data revealed the ability of grape skin binding to amylase
      belonged to static quenching mechanism with a complex formation and there was
      only one binding site in alpha-amylase for grape skin extract. Docking study
      showed a best pose with total energy value of -118.3 kJ/mol and grape skin
      extract interacted with side chain of Asp300 with hydrogen bonds and Van der
      Waals forces. This preliminary observation provides the basis for further
      evaluation of the suitability of grape skin extract as natural inhibitor with
      potential health benefits.

PMID- 24128470
TI  - Effects of a highly resistant rice starch and pre-incubation temperatures on the
      physicochemical properties of surimi gel from grass carp (Ctenopharyn Odon
      Idellus).
AB  - The effects of a specific rice starch (SRS), containing highly resistant starch
      (RSIII), on gel properties of grass carp (Ctenopharyngodon idella) and the
      influence of five levels of SRS (0%, 2%, 4%, 6%, and 8%w/w) on gel
      physicochemical properties at three different pre-incubation temperatures (4 
      degrees C, 25  degrees C, and 40  degrees C) were investigated. Gels with
      increasing amounts of SRS addition showed lower expressible water contents and
      cooking loss values than did control gels. SDS gel electrophoresis revealed no
      changes in protein patterns, regardless of different SRS-added levels at the same
      pre-incubation temperature, but an evident decrease in the MHC when the pre
      incubation temperature increased. The texture properties, colour attributes, SEM
      were optimal in the treatments containing 4%w/w SRS at the pre-incubation
      temperature 25  degrees C. Thus, the optimum SRS addition level and pre
      incubation temperature are proposed to be 4%w/w and 25  degrees C, respectively.

PMID- 24128471
TI  - Production of quercetin, kaempferol and their glycosidic derivatives from the
      aqueous-organic extracted residue of litchi pericarp with Aspergillus awamori.
AB  - Our previous work exhibited Aspergillus awamori fermentation of the litchi
      pericarp increased significantly antioxidant activity and DNA protection effect.
      In this present study, the litchi pericarp and its aqueous-organic extracted
      residues were fermented by A. awamori in order to elucidate the enhanced
      beneficial effects. The study identified that rutin which present in litchi
      pericarp could be deglycosylated to form quercetin and quercetin-3-glucoside
      after the fermentation. Application the standard compounds (rutin, quercetin 3
      glucoside, quercetin, kaempferol-3-glucoside and kaempferol) further revealed the
      effective biotransformation by A. awamori fermentation. It was hypothesised that
      rutin was initially dehydroxylated to form kaempferol-3-rutinoside and then
      deglycosylated to form kaempferol-3-glucoside and kaempferol. To our best
      knowledge, it is the first report on dehydroxylated effect of polyphenols caused
      by A. awamori fermentation. Thus, A. awamori fermentation can provide an
      effective way to produce health benefiting value-added products from litchi
      pericarp in food industry. 

PMID- 24128472
TI  - Nondestructive measurement of total volatile basic nitrogen (TVB-N) in pork meat
      by integrating near infrared spectroscopy, computer vision and electronic nose
      techniques.
AB  - Total volatile basic nitrogen (TVB-N) content is an important reference index for
      evaluating pork freshness. This paper attempted to measure TVB-N content in pork
      meat using integrating near infrared spectroscopy (NIRS), computer vision (CV),
      and electronic nose (E-nose) techniques. In the experiment, 90 pork samples with
      different freshness were collected for data acquisition by three different
      techniques, respectively. Then, the individual characteristic variables were
      extracted from each sensor. Next, principal component analysis (PCA) was used to
      achieve data fusion based on these characteristic variables from 3 different
      sensors data. Back-propagation artificial neural network (BP-ANN) was used to
      construct the model for TVB-N content prediction, and the top principal
      components (PCs) were extracted as the input of model. The result of the model
      was achieved as follows: the root mean square error of prediction (RMSEP) = 2.73
      mg/100g and the determination coefficient (R(p)(2)) = 0.9527 in the prediction
      set. Compared with single technique, integrating three techniques, in this paper,
      has its own superiority. This work demonstrates that it has the potential in
      nondestructive detection of TVB-N content in pork meat using integrating NIRS, CV
      and E-nose, and data fusion from multi-technique could significantly improve TVB
      N prediction performance.

PMID- 24128473
TI  - Migration of odorous compounds from adhesives used in market samples of food
      packaging materials by chromatography olfactometry and mass spectrometry (GC-O
      MS).
AB  - Adhesives are commonly used in the manufacture of multilayer food packaging
      materials. Although they are not in direct contact with the packed food, their
      compounds may migrate from the adhesive through the substrates to the food. The
      aim of this work is to determine the migrant concentration in order to evaluate
      the possible human risk and also to determine if this migration could affect the
      organoleptic properties of packed food. For this purpose, a total of 12 market
      samples of multilayer materials (laminates) for packaging dry food (tomatoes,
      cakes, cookies, breadcrumbs, flour or salt) or fresh food (pizza and pastry)
      produced with 5 different adhesives were analysed by GC-O-MS. A total of 25
      different compounds from adhesives were detected in these laminates. Seventy-six
      percentage of these compounds migrated into a dry food simulant (Tenax(r)).
      Furthermore, compounds with concentrations below the MS detection limit were
      detected by sniffers with a high modified frequency (MF%). Acetic acid, butyric
      acid and cyclohexanol with vinegar, cheese and camphor odours were the most
      abundant compounds. All migration data were below the specific migration limits
      (SML) and threshold toxicological concern (TTC) recommended values according to
      the Cramer classification. 

PMID- 24128474
TI  - Structural and functional properties of alkali-treated high-amylose rice starch.
AB  - Native starches were isolated from mature grains of high-amylose transgenic rice
      TRS and its wild-type rice TQ and treated with 0.1% and 0.4% NaOH for 7 and 14
      days at 35  degrees C. Alkali-treated starches were characterised for structural
      and functional properties using various physical methods. The 0.1% NaOH treatment
      had no significant effect on structural and functional properties of starches
      except that it markedly increased the hydrolysis of starch by amylolytic enzymes.
      The 0.4% NaOH treatment resulted in some changes in structural and functional
      properties of starches. The alkali treatment affected granule morphology and
      decreased the electron density between crystalline and amorphous lamellae of
      starch. The effect of alkali on the crystalline structure including long- and
      short-range ordered structure was not pronounced. Compared with control starch,
      alkali-treated TRS starches had lower amylose content, higher onset and peak
      gelatinisation temperatures, and faster hydrolysis of starch by HCl and
      amylolytic enzymes.

PMID- 24128475
TI  - Targeted analysis of polyphenol metabolism during development of hop (Humulus
      lupulus L.) cones following treatment with prohexadione-calcium.
AB  - Hops (Humulus lupulus), a main ingredient in beer, are valued as a source of
      bitter flavour and biologically active polyphenols. We treated immature hop cones
      with prohexadione-calcium (Pro-Ca), a flavanone-3-hydroxylase (F3H) inhibitor, to
      perturb the flavonoid pathway, and conducted a targeted analysis of 29 compounds
      from the phenolic acid, flavonoid, and terpenophenolic pathways, using photodiode
      array (UHPLC-PDA), and time of flight mass spectrometry (LC-TOF-MS) analysis. Hop
      cones were analysed over four stages of development spanning 22days following Pro
      Ca treatment. The content of terpenophenolics as well as metabolic precursors
      upstream from F3H significantly increased, and levels of flavonoid products
      downstream from F3H decreased. The methods developed here serve to compliment
      flavour analysis of polyphenol rich foods, and our results suggest ways to
      improve upon traditional agricultural methods to produce hops with altered
      chemical profiles. 

PMID- 24128476
TI  - Optimization of a blanching step to maximize sulforaphane synthesis in broccoli
      florets.
AB  - A blanching step was designed to favor sulforaphane synthesis in broccoli.
      Blanching was optimised through a central composite design, and the effects of
      temperature (50-70  degrees C) and immersion time in water (5-15 min) on the
      content of total glucosinolates, glucoraphanin, sulforaphane, and myrosinase
      activity were determined. Results were analysed by ANOVA and the optimal
      condition was determined through response surface methodology. Temperature
      between 50 and 60  degrees C significantly increased sulforaphane content
      (p<0.05), whilst blanching at 70 and 74  degrees C diminished significantly this
      content, compared to fresh broccoli. The optimal blanching conditions given by
      the statistical model were immersion in water at 57  degrees C for 13 min;
      coinciding with the minimum glucosinolates and glucoraphanin content, and with
      the maximum myrosinase activity. In the optimal conditions, the predicted
      response of 4.0 MUmol sulforaphane/g dry matter was confirmed experimentally.
      This value represents a 237% increase with respect to the fresh vegetable.

PMID- 24128477
TI  - Development and evaluation of novel flavour microcapsules containing vanilla oil
      using complex coacervation approach.
AB  - A novel flavour microcapsule containing vanilla oil (VO) was developed using
      complex coacervation approach, aimed to control release of VO and enhance its
      thermostability for spice application in food industry. Viscosity of chitosan
      (CS) and VO/CS ratio were optimised for fabrication of microcapsules. The flavour
      microcapsules were evaluated by scanning electron micrograph (SEM), laser
      confocal microscopy (LSCM), particle size analyser, infrared spectrometer (FT
      IR), thermal analysis and controlled-release analysis. The microcapsules were in
      spherical with good dispersibility when moderate viscosity CS was used. 94.2% of
      encapsulation efficiency was achieved in VO/CS ratio of 2:1. The FT-IR study
      proved chemical cross-linking reaction occurred between genipin and chitosan, but
      a physical interaction between CS and VO. A core-shell structure of microcapsule
      was confirmed by LSCM, which was beneficial to improve the thermostability of VO
      in microcapsule. Moreover, VO could be remained about 60% in the microcapsules
      after release for 30 days, which demonstrated the flavour microcapsules had good
      potential to serve as a high quality food spice with long residual action and
      high thermostability.

PMID- 24128478
TI  - Identification of additive components in powdered milk by NIR imaging methods.
AB  - The express assay of excessive additives in powdered milk is of vital necessity,
      especially during industrial production. Near-infrared microscopy provides
      chemical information on the spatial distribution and cluster side of components
      in milk-based products when materials are mixed together. Distributions of two
      additive components and one banned chemical in powdered milk were simulated in
      this study. The distribution of inorganic additive ZnSO4 was identified using the
      relationship imaging mode. The distribution image of lactose was obtained by
      assigning the wavenumber region and by using principal component analysis coupled
      with correlation coefficient imaging. In addition, classical least square
      regression was employed to quantify the banned additive, melamine, in the
      powdered milk. Lastly, the detection limit of melamine in powdered milk was
      determined using the relationship imaging mode. 

PMID- 24128479
TI  - Color evaluation of seventeen European unifloral honey types by means of
      spectrophotometrically determined CIE L*Cab*h(ab) degrees  chromaticity
      coordinates.
AB  - CIE (Commission Internationale de l'Eclairage) L(*)Cab(*)h(ab) degrees  color
      coordinates for 305 samples of 17 unifloral honeys types (asphodel, buckwheat,
      black locust, sweet chestnut, citrus, eucalyptus, Garland thorn, honeydew,
      heather, lime, mint, rapeseed, sage, strawberry tree, sulla flower, savory and
      thistle) from different geographic locations in Europe were
      spectrophotometrically assessed and statistically evaluated. Preliminary
      separation of unifloral honeys was obtained by means of L(*)-C(ab)(*) color
      coordination correlation. Hierarchical Cluster Analysis (HCA) revealed an
      expected segregation of the honeys types according to their chromatic
      characteristics. Principal Component Analysis (PCA) allowed to obtain a more
      defined distinction of the 17 unifloral honey types, particularly when using 3D
      graphics. CIE L(*)C(ab)(*)hab(*) color coordinates were useful for the
      identification of several honey types. The proposed method represents a simple
      and efficient procedure that can be used as a basis for the authentication of
      unifloral honeys worldwide.

PMID- 24128480
TI  - Phenolic composition and antioxidant activity in sparkling wines: modulation by
      the ageing on lees.
AB  - Sparkling wines (SW) have a special biological ageing on lees that is performed
      using two distinct methods: in the bottle (Champenoise) or in isobaric tanks
      (Charmat method). The objective of this study was to compare the levels of
      phenolic compounds, beta-Glucosidase and antioxidant activity during the ageing
      on lees, in samples of SW produced at industrial scale by both methods. The beta
      Glucosidase activity has been constant over time, showing a close relationship
      with all the polyphenols studied (resveratrol, piceid, tyrosol, gallic, caffeic
      and ferulic acids), which were affected by the sur lie time. With these cross
      reactions, the biological properties of the SW were also modulated. The results
      showed that the long period of ageing decreased the antioxidant potential in all
      samples. This work demonstrates that the sur lie is more important than the
      production method itself, due to its ability to modulate the necessary changes to
      achieve the specific objective. 

PMID- 24128481
TI  - Recent developments in application of stable isotope analysis on agro-product
      authenticity and traceability.
AB  - With the globalisation of agro-product markets and convenient transportation of
      food across countries and continents, the potential for distribution of mis
      labelled products increases accordingly, highlighting the need for measures to
      identify the origin of food. High quality food with identified geographic origin
      is a concern not only for consumers, but also for agriculture farmers, retailers
      and administrative authorities. Currently, stable isotope ratio analysis in
      combination with other chemical methods gradually becomes a promising approach
      for agro-product authenticity and traceability. In the last five years, a growing
      number of research papers have been published on tracing agro-products by stable
      isotope ratio analysis and techniques combining with other instruments. In these
      reports, the global variety of stable isotope compositions has been investigated,
      including light elements such as C, N, H, O and S, and heavy isotopes variation
      such as Sr and B. Several factors also have been considered, including the
      latitude, altitude, evaporation and climate conditions. In the present paper, an
      overview is provided on the authenticity and traceability of the agro-products
      from both animal and plant sources by stable isotope ratio analysis. 

PMID- 24128482
TI  - Antioxidant activity and phenolic profile of different parts of Bene (Pistacia
      atlantica subsp. kurdica) fruits.
AB  - Five genotypes of Bene were collected from West Azerbaijan, Kurdistan, Kermanshah
      and Ilam provinces, Iran. Total phenolic and flavonoid contents were determined
      and antioxidant activity of the extracts were measured using different assays:
      FRAP, nitric oxide radical scavenging and DPPH. Total phenolic and flavonoid
      contents of the hull extracts were significantly higher than shell and kernel
      extracts. In hull extracts, positive correlation coefficient was observed between
      total phenolic content and FRAP (R(2) = 0.98) and DPPH (R(2) = 0.66) assays. The
      results showed that, the highest antioxidant activity of hull extract may be
      attributed to higher total phenolic content. Analyzing the phenolic composition
      using HPLC, sinapic acid, vanillic acid and p-hydroxybenzoic acid were found in
      hull and shell extracts of all genotypes. Among all the genotypes studied here,
      B4 showed the highest phenolic content and antioxidant activity.

PMID- 24128483
TI  - Chemical and sensory quality of fresh pomegranate fruits exposed to gamma
      radiation as quarantine treatment.
AB  - The U.S. Department of Agriculture in February 2012 approved the import of fresh
      pomegranates subjected to irradiation as a quarantine procedure with a minimum
      absorbed dose of 0.4kGy against different pests. This study evaluated the
      application of different gamma-irradiation doses (0.4, 1, and 2kGy) in fresh
      pomegranate fruits and their effect on the chemical and sensory characteristics.
      The total soluble solids, titratable acidity, and pH values remained unaffected
      up to 1kGy treatment. Irradiation caused a significant decrease in the total
      anthocyanins and phenolic content. A strong positive correlation was observed
      among the antioxidant activities, total phenolics and anthocyanin contents. In
      general, a stronger preference was shown by sensory panelists for the juice from
      irradiated fruits. This study provides research-based information about the
      application of irradiation as a quarantine disinfestation treatment to enhance
      the marketing and consumer acceptance of pomegranates. 

PMID- 24128484
TI  - Suitability of three-dimensional synchronous fluorescence spectroscopy for
      fingerprint analysis of honey samples with reference to their phenolic profiles.
AB  - The suitability of a right-angle geometry three-dimensional synchronous
      fluorescence spectroscopy (3D-SFS) for the differentiation and classification of
      different honey types, including acacia, buckwheat, heather, linden, multiflower
      and rape honeys, was evaluated with reference to their phenolic profiles. The
      fraction of phenolic compounds was initially isolated and pre-concentrated from
      analyzed samples by means of polymeric reversed phase Strata X solid phase
      extraction (SPE) cartridges. A thoughtful analysis of 3D-SF spectra of resulting
      methanolic extracts of honey samples containing the separated fraction of
      phenolics and standards of phenolic acids and flavonoids revealed that the
      proposed methodology based on SPE and 3D-SFS is capable of discriminating honey
      samples due to different floral sources in a fast and straightforward way. 

PMID- 24128485
TI  - Assessment of pomegranate wine lees as a valuable source for the recovery of
      (poly)phenolic compounds.
AB  - Wine lees are the residue formed at the bottom of recipients containing wine
      after fermentation and are mainly composed of yeast. They can be applied for the
      recovery of value-added phytochemicals owing to the ability of yeast to form
      molecular interactions with (poly)phenolic compounds. This study aimed to
      evaluate the potential use of lees obtained as by-products after winemaking of
      pomegranate (Punica granatum L.) juice. Pomegranate wine lees showed high both
      phenolic content (about 30 mg GAE/g dry matter) and antioxidant capacity by DPPH
      and ABTS(+) assays. The phytochemical screening of this by-product by UHPLC-ESI
      MS(n) allowed the identification of up to 39 chemicals, being hydrolysable
      tannins and anthocyanins the predominant structures. Ellagic acid and gallic acid
      were present in high amounts. In addition, mineral composition was also assessed.
      Overall, pomegranate wine lees resulted in a promising source for the recovery of
      bioactive polyphenols with potential applications in different industrial fields.

PMID- 24128486
TI  - Antioxidant activity of penta-oligogalacturonide, isolated from haw pectin,
      suppresses triglyceride synthesis in mice fed with a high-fat diet.
AB  - To expand application of hawthorn (Crataegus pinnatifida Bge) fruit, the
      antioxidant and anti-lipidemic effects of haw pectin penta-oligogalacturonide
      (HPPS) prepared from hawthorn fruit were investigated in vitro and in mice. HPPS
      exhibited concentration-dependent scavenging activities against superoxide anion,
      hydroxyl and DPPH radicals. Additionally, HPPS supplementation significantly
      enhanced the antioxidant enzyme activities of superoxide dismutase, catalase,
      glutathione peroxidase, increased the total antioxidant capacity and the levels
      of glutathione, but lowered the malondialdehyde content in the liver of high-fat
      fed mice. Furthermore, HPPS significantly decreased the TG levels, the activity
      and the mRNA and protein levels of glycerol 3-phosphate acyltransferase (GPAT)
      and phosphatidate phosphohydrolase (PAP) in mice livers. Moreover, liver
      steatosis of mice associated with diffuse hepatocyte ballooning induced by a high
      fat diet was markedly improved by a dose of 300 mg/kg HPPS-consumption. The
      results revealed that HPPS might be applicable as a dietary supplement for the
      prevention of fatty liver and oxidative damage.

PMID- 24128487
TI  - Rapid identification of adulterated cow milk by non-linear pattern recognition
      methods based on near infrared spectroscopy.
AB  - More than 800 representative milk samples, which consisted of 287 raw cow milk
      samples from different pastures surrounding Shanghai of China and 526
      adulteration milk samples containing different pseudo proteins and thickeners,
      were collected and designed to demonstrate a method for rapidly discriminating
      adulterated milks based on near infrared (NIR) spectra. The NIR classification
      models were built by two non-linear supervised pattern recognition methods of
      improved support vector machine (I-SVM) and improved and simplified K nearest
      neighbours (IS-KNN). Uniform design theory was applied to optimize the parameters
      of SVM and thus the computation amount was reduced 90%. Both two methods exhibit
      good adaptability in discriminating adulterated milks from raw cow milks. Further
      investigation showed that the correction ratio for discriminating milk samples
      increased with the increasing of adulteration solutions' level in the adulterated
      milk. The concentration of adulterants is an important factor of influencing milk
      discrimination results of the NIR pattern recognition models. The results
      demonstrated the usefulness of NIR spectra combined with non-linear pattern
      recognition methods as an objective and rapid method for the authentication of
      complicated raw cow milks. 

PMID- 24128488
TI  - Precise determination of strontium isotope ratios by TIMS to authenticate tomato
      geographical origin.
AB  - Thermal Ionisation Mass Spectrometry (TIMS) was applied to discriminate a total
      of 118 tomato samples (berries, "passata", tinned tomatoes, sauce, double and
      triple concentrate) coming from two different countries. The TIMS technique gave
      significantly different results for the (87)Sr/(86)Sr ratios and delta0/00 values
      between Chinese and Italian tomato samples, irrespective of the treatment type.
      This technique proved to be a "robust" method, suitable for a precise
      discrimination of the two geographical origins. TIMS was able, within the Italian
      samples, to discriminate different geographical production areas, by virtue of
      different (87)Sr/(86)Sr ratios and delta0/00 values. This technique could be
      employed in the field of food safety and quality, as a profitable tool for
      authenticating tomato geographical origin. 

PMID- 24128489
TI  - Mode of endosperm and wholemeal arabinoxylans solubilisation during rye
      breadmaking: genotypic diversity in the level, substitution degree and
      macromolecular characteristics.
AB  - Insight into solubilisation mechanisms of rye arabinoxylans during breadmaking is
      important for understanding the biochemical processes that affect bread
      attributes. Purified ethanol precipitated water-extractable arabinoxylans (WE-AX)
      and residual unextractable counterparts (WU-AX) were isolated from rye flours and
      resulting breads. While the endosperm flours had lower endoxylanase activities
      and higher arabinose-to-xylose ratios of WU-AX than those of corresponding
      wholemeals, there were not any significant differences between them in the mean
      amounts of WU-AX hydrolysed during breadmaking. Nevertheless, they were highly
      affected by rye cultivar used for breadmaking. On average, 42% and 36% of WU-AX
      were recovered in bread WE-AX fraction, causing its 11% and 8% increase,
      respectively for endosperm and wholemeal breads. Bread WE-AX, however, had lower
      molecular weights than those of starting flours, implying chains
      depolymerisation. Degree of AX solubilisation depends mainly on rye genotype
      used, determining combined effect of enzymatic and acid hydrolyses, associations
      and fine structure of AX. 

PMID- 24128490
TI  - Quantitative studies on structure-ORAC relationships of anthocyanins from
      eggplant and radish using 3D-QSAR.
AB  - The 3-dimensional quantitative structure activity relationship (3D-QSAR) models
      were established from 21 anthocyanins based on their oxygen radical absorbing
      capacity (ORAC) and were applied to predict anthocyanins in eggplant and radish
      for their ORAC values. The cross-validated q(2)=0.857/0.729, non-cross-validated
      r(2) = 0.958/0.856, standard error of estimate = 0.153/0.134, and F =
      73.267/19.247 were for the best QSAR (CoMFA/CoMSIA) models, where the correlation
      coefficient r(2)pred = 0.998/0.997 (>0.6) indicated a high predictive ability for
      each. Additionally, the contour map results suggested that structural
      characteristics of anthocyanins favourable for the high ORAC. Four anthocyanins
      from eggplant and radish have been screened based on the QSAR models.
      Pelargonidin-3-[(6''-p-coumaroyl)-glucosyl(2 -> 1)glucoside]-5-(6''-malonyl)
      glucoside, delphinidin-3-rutinoside-5-glucoside, and delphinidin-3-[(4''-p
      coumaroyl)-rhamnosyl(1 -> 6)glucoside]-5-glucoside potential with high ORAC based
      the QSAR models were isolated and also confirmed for their relative high
      antioxidant ability, which might attribute to the bulky and/or electron-donating
      substituent at the 3-position in the C ring or/and hydrogen bond donor
      group/electron donating group on the R1 position in the B ring.

PMID- 24128491
TI  - Characterisation of a novel softened rice product.
AB  - We developed a novel softened rice by permeating rice with enzymes that catalyse
      its decomposition. Herein, we characterised the softened rice (SR) and compared
      it to normal cooked rice (CR) and rice gruel (RG). SR resembled CR but not RG in
      appearance. Texture analysis showed that SR was the least firm, adhesive, and
      cohesive of the three rice preparations. SR contained almost the same amount of
      nutrition per unit mass as CR and twofold as much as RG. Analysis of digests of
      energy-equivalent amounts of the three rice preparations indicated that SR
      digests had the lowest quantity of residue and highest quantity of dissolved
      carbohydrate, maltose and glucose. The molecular weight (MW) range of SR
      constituents was 10(3)-10(5), whilst those of CR and RG constituents were mainly
      10(5)-10(6). These results suggested that enzymatic decomposition of SR improves
      ease of eating, nutrition value, and digestibility at once. 

PMID- 24128492
TI  - Flavour generation during commercial barley and malt roasting operations: a time
      course study.
AB  - The roasting of barley and malt products generates colour and flavour, controlled
      principally by the time course of product temperature and moisture content.
      Samples were taken throughout the industrial manufacture of three classes of
      roasted product (roasted barley, crystal malt and black malt) and analysed for
      moisture content, colour and flavour volatiles. Despite having distinct flavour
      characteristics, the three products contained many compounds in common. The
      product concentrations through manufacture of 15 flavour compounds are used to
      consider the mechanisms (Maillard reaction, caramelisation, pyrolysis) by which
      they were formed. The use of water sprays resulted in transient increases in
      formation of certain compounds (e.g., 2-cyclopentene-1,4-dione) and a decrease in
      others (e.g., pyrrole). The study highlights rapid changes in colour and
      particularly flavour which occur at the end of roasting and onwards to the
      cooling floor. This highlights the need for commercial maltsters to ensure
      consistency of procedures from batch to batch. 

PMID- 24128493
TI  - Galactooligosaccharides formation during enzymatic hydrolysis of lactose: towards
      a prebiotic-enriched milk.
AB  - The formation of galactooligosaccharides (GOS) in skim milk during treatment with
      several commercial beta-galactosidases (Bacillus circulans, Kluyveromyces lactis
      and Aspergillus oryzae) was analysed in detail, at 4 and 40 degrees C. The
      maximum GOS concentration was obtained at a lactose conversion of approximately
      40-50% with B. circulans and A. oryzae beta-galactosidases, and at 95% lactose
      depletion for K. lactis beta-galactosidase. Using an enzyme dosage of 0.1% (v/v),
      the maximum GOS concentration with K. lactis beta-galactosidase was achieved in 1
      and 5h at 40 and 4  degrees C, respectively. With this enzyme, it was possible to
      obtain a treated milk with 7.0 g/L GOS - the human milk oligosaccharides (HMOs)
      concentration is between 5 and 15 g/L--and with a low content of residual lactose
      (2.1g/L, compared with 44-46 g/L in the initial milk sample). The major GOS
      synthesised by this enzyme were 6-galactobiose [Gal-beta(1 -> 6)-Gal],
      allolactose [Gal-beta(1 -> 6)-Glc] and 6'-O-beta-galactosyl-lactose [Gal-beta(1 
      > 6)-Gal-beta(1 -> 4)-Glc].

PMID- 24128494
TI  - Fingerprinting of anthocyanins from grapes produced in Brazil using HPLC-DAD-MS
      and exploratory analysis by principal component analysis.
AB  - The anthocyanin profile was studied for 11 types of grapes of different varieties
      and geographical origins, including 10 wine grape varieties (Vitis vinifera) and
      one hybrid variety. Twenty anthocyanins were identified by means of the
      absorbance spectrum and fragmentation pattern by tandem mass spectrometry. The
      multivariate method of principal component analysis (PCA) was used to evaluate
      differences amongst the cultivars. The results show the hybrid grape separated
      from a cluster represented by viniferas grapes, mainly due to anthocyanin
      diglucosides. Within this group, it was possible to discriminate the different
      wine grapes. Clusters discriminating according to geographical origin were not
      observed. 

PMID- 24128495
TI  - Characterisation of honeys according to their content of phenolic compounds using
      high performance liquid chromatography/tandem mass spectrometry.
AB  - A simple, fast and specific high performance liquid chromatography separation
      with an electro-spray ionisation tandem mass spectrometry detection in a negative
      single reaction ion monitoring scan mode was developed and used for the
      characterization of Polish honeys according to the content of phenolic acids,
      including caffeic, chlorogenic, p-coumaric, ferulic, homogentisic, p
      hydroxybenzoic and vanillic acids, and flavonoids, i.e., apigenin, genistein,
      hesperetin, kaempferol, luteolin, rhamnetin, rutin, tricetin and quercetin.
      Target compounds were isolated and pre-concentrated from the honey matrix by
      means of the solid phase extraction using Strata X (500mg) cartridges. Analysed
      honeys did not contain tricetin and genistein. Hesperetin was determined for the
      first time in heather and linden honeys while rutin in rape honey. 

PMID- 24128496
TI  - Quality improvement of rice noodle restructured with rice protein isolate and
      transglutaminase.
AB  - In an effort to improve the properties of rice dough and quality of gluten-free
      rice noodle, transglutaminase (TGase) and rice protein isolate (RPI) were applied
      to rice noodle making process. The storage and loss moduli of rice dough
      increased by TGase treatment, whereas they decreased with RPI supplementation.
      The combined treatment of RPI+TGase on rice dough fully recovered the reduced
      moduli caused by RPI only supplementation to control level, and increased most of
      viscosity parameters of rice noodle in RVA analysis. This additional treatment of
      TGase also increased development time, and maximum and peak torques of RPI
      supplemented rice dough in Mixolab(r) analysis. Cooking loss and water turbidity
      of rice noodle decreased by 54.8% and 66.6%, respectively, after TGase+RPI
      treatment. Scanning electron micrographs showed cracked noodle surface became
      smoothed with TGase treatment, which was more obvious with RPI+TGase treatment.
      These results suggest RPI+TGase treatment could improve the quality of rice
      noodle without the use of gluten-like ingredients. 

PMID- 24128497
TI  - Novel non-invasive distribution measurement of texture profile analysis (TPA) in
      salmon fillet by using visible and near infrared hyperspectral imaging.
AB  - This study developed a pushbroom visible and near-infrared hyperspectral imaging
      system in the wavelength range of 400-1758 nm to determine the spatial
      distribution of texture profile analysis (TPA) parameters of salmon fillets. Six
      TPA parameters (hardness, adhesiveness, chewiness, springiness, cohesiveness, and
      gumminess) were analysed. Five spectral features (mean, standard deviation, skew,
      energy, and entropy) and 22 image texture features obtained from graylevel co
      occurrence matrix (GLCM) were extracted from hyperspectral images. Quantitative
      models were established with the extracted spectral and image texture signatures
      of samples based on partial least squares regression (PLSR). The results
      indicated that spectral features had better ability to predict TPA parameters of
      salmon samples than image texture features, and Spectral Set I (400-1000 nm)
      performed better than Spectral II (967-1634 nm). On the basis of the wavelengths
      selected by regression coefficients of PLSR models, instrumental optimal
      wavelengths (IOW) and predictive optimal wavelengths (POW) were further chosen to
      reduce the high dimensionality of the hyperspectral image data. Our results show
      that hyperspectral imaging holds promise as a reliable and rapid alternative to
      traditional universal testing machines for measuring the spatial distribution of
      TPA parameters.

PMID- 24128498
TI  - Quantitation and bitter taste contribution of saponins in fresh and cooked white
      asparagus (Asparagus officinalis L.).
AB  - A sensitive HPLC-MS/MS method was developed enabling the simultaneous
      quantification of bitter-tasting mono- and bidesmosidic saponins in fresh and
      processed asparagus (Asparagus officinalis L.). Based on quantitative data and
      bitter taste recognition thresholds, dose-over-threshold factors were determined
      for the first time to determine the bitter impact of the individual saponins.
      Although 3-O-[alpha-L-rhamnopyranosyl-(1->2)-alpha-L-rhamnopyranosyl-(1 -> 4)
      beta-D-glucopyranosyl]-(25R/S)-spirost-5-ene-3beta-ol was found based on dose
      over-threshold factors to be the predominant bitter saponin in raw asparagus
      spears, 3-O-[alpha-L-rhamnopyranosyl-(1 -> 2)-{alpha-L-rhamnopyranosyl-(1 -> 4)}
      beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-(25R)-22-hydroxyfurost-5-ene
      3beta,26-diol, 3-O-[alpha-L-rhamnopyranosyl-(1 -> 2)-{alpha-L-rhamnopyranosyl-(1 
      > 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-(25S)-22-hydroxyfurost
      5-ene-3beta,26-diol, and (25R)- and (25S)-furost-5-en-3beta,22,26-triol-3-O
      [alpha-L-rhamnopyranosyl-(1 -> 4)-beta-D-glucopyranoside]-26-O-beta-D
      glucopyranoside were found as key bitter contributors after cooking.
      Interestingly, the monodesmosidic saponins 5a/b were demonstrated for the first
      time to be the major contributor to the bitter taste of fresh asparagus spears,
      while the bidesmosides 1a/b and 2a/b may be considered the primary determinants
      for the bitter taste of cooked asparagus.

PMID- 24128499
TI  - The salt and lipid composition of model cheeses modifies in-mouth flavour release
      and perception related to the free sodium ion content.
AB  - Reducing salt and lipid levels in foodstuffs without any effect on acceptability
      is a major challenge, particularly because of their interactions with other
      ingredients. This study used a multimodal approach to understand the effects of
      changes to the composition of model cheeses (20/28, 24/24, 28/20 lipid/protein
      ratios, 0% and 1% added NaCl) on sodium ion mobility ((23)Na NMR), in-mouth
      sodium release and flavour perception. An increase in the salt content decreased
      cheese firmness and perceived hardness, and increased sodium ion mobility, in
      vivo sodium release and both saltiness and aroma perception. With the same amount
      of salt, a lower lipid/protein ratio increased the firmness of the cheeses,
      perceived hardness, and decreased sodium ion mobility, in vivo sodium release,
      saltiness and aroma perception. These findings suggest on one hand that it could
      be possible to increase saltiness perception by varying cheese composition, thus
      inducing differences in sodium ion mobility and in free sodium ion concentration,
      leading to differences in in-mouth sodium release and saltiness perception, and
      on the other hand that the reformulation of foods in line with health guidelines
      needs to take account of both salt content and the lipid/protein ratio. 

PMID- 24128500
TI  - Application of the solvent extraction technique to investigation of the anti
      inflammatory activity of adlay bran.
AB  - The current study utilised a bioassay-directed chemical analysis scheme to screen
      the anti-inflammatory activity of fractions and compounds from adlay bran (AB).
      Liquid-liquid extraction couple with liquid chromatography-mass spectrometry (LC
      MS) was applied to the isolation, analysis and identification of active
      components in AB samples. Ethanol extracts of AB (ABE) and ethyl acetate extracts
      AB (ABEa) were obtained and further partitioned with different solvents. The
      results showed that among all 16 kinds of fractions from ABE and ABEa, ABEa-Ea-B
      (80% Ea/n-hexane sub-fraction from ABE-Ea) had the most potent inhibitory effects
      on NO production, iNOS and COX-2 expressions, and proinflammatory IL-6 and TNF
      alpha secretion in lipopolysaccharide-activated RAW264.7 cells system.
      Mechanistic data from luciferase reporter-gene assay revealed that the anti
      inflammatory action of ABEa-Ea-B may be associated with inhibition of NF-kB
      transcriptional activity. Notably, tangeretin, nobiletin, and p-hydroxybenzoic
      acid were found to be the main active compounds for the anti-inflammatory
      properties in ABEa-Ea-B. 

PMID- 24128501
TI  - Effect of CO2 deastringency treatment on flesh disorders induced by mechanical
      damage in persimmon. Biochemical and microstructural studies.
AB  - Manifestation of flesh browning while commercialising 'Rojo Brillante' persimmon
      is one of the main causes of postharvest loss. It is known that mechanical damage
      is a decisive factor for browning development and that astringent fruit is less
      sensitive to this disorder than fruit submitted to a CO2 deastringency treatment
      under standard conditions (24h, 95% CO2, 20  degrees C). However, there is no
      information available about the mechanism behind this alteration. In the present
      study, we evaluated the effect of treatment with high CO2 concentrations applied
      for 0-40 h on the incidence of mechanical impact-induced flesh disorders using
      biochemical, chromatographic and microstructural techniques. Our results show
      that the longer the CO2 exposure, the higher the incidence and the greater the
      severity browning. A deastringency treatment with CO2 results in O2(-)
      accumulation in fruit, which is greater the longer treatment is. However,
      mechanical damage triggers the browning manifestation, resulting in the
      accumulation of both O2(-) and H2O2. In this oxidative stress state, which must
      be greater as higher the level of O2(-) previously accumulated in the
      deastringency treatment, insoluble tannins initially uncolour, undergo an
      oxidation process and turn red-brown, observed as flesh browning. Moreover, we
      identified a new disorder, "pinkish-bruising", which is manifested in astringent
      fruit. The mechanism of this alteration, also associated with mechanical damage,
      seems similar to that of browning, but the oxidation process would affect soluble
      tannins.

PMID- 24128502
TI  - Study of the influence of yeast inoculum concentration (Yarrowia lipolytica and
      Kluyveromyces lactis) on blue cheese aroma development using microbiological
      models.
AB  - Yarrowia lipolytica and Kluyveromyces lactis occur as part of Stilton cheese
      microflora yet are not controlled during production. This study investigated the
      influence of their inoculum concentration on aroma production. Models of Y.
      lipolytica and K. lactis, with Penicillium roqueforti, were analysed using
      instrumental and sensory analysis. Different concentrations of Y. lipolytica
      produced important changes in the aroma profiles of microbiological models,
      analysed by solid-phase microextraction (SPME GC-MS). Sensory analysis with
      discrimination tests showed differences were detectable via human perception but
      did not concern the similarity to blue cheese odour. Increasing the inoculum
      concentration of K. lactis resulted in decreased variation between replicates.
      Partial least squares (PLS) regression on Flash profile data showed models
      inoculated with low concentrations of K. lactis exhibited blue cheese-related
      attributes, associated with increased ketone production. Results suggest that
      controlling the amount of Y. lipolytica and K. lactis during production offers
      potential to manipulate blue cheese aroma development. 

PMID- 24128503
TI  - Effect of initial protein concentration and pH on in vitro gastric digestion of
      heated whey proteins.
AB  - The in vitro digestion of heated whey protein aggregates having different
      structure and physicochemical properties was evaluated under simulated gastric
      conditions. Aggregates were formed by heating whey protein isolates (WPI) at 3-9%
      w/w initial protein concentration and pH 3.0-7.0. Results showed that high
      protein concentration led to formation of larger WPI aggregates with fewer
      remaining monomers. Aggregates formed at high protein concentrations showed
      slower degradation rate compared to those formed at low protein concentration.
      The effect of initial protein concentration on peptide release pattern was not
      apparent. Heating pH was a significant factor affecting digestion pattern. At pH
      above the isoelectric point, the majority of the proteins involved in the
      aggregation, and aggregates formed at pH 6.0 were more susceptible to pepsin
      digestion than at pH 7.0. At acidic conditions, only small amount of proteins was
      involved in the aggregation and heated aggregates were easily digested by pepsin,
      while the remaining unaggregated proteins were very resistant to gastric
      digestion. The potential physiological implication of these results on satiety
      was discussed. 

PMID- 24128504
TI  - The endogenous GABA bioactivity of camel, bovine, goat and human milks.
AB  - GABA orally administered has several beneficial effects on health, including the
      regulation of hyperglycaemic states in humans. Those effects are similar to the
      effects reported for camel milk (CMk); however, it is not known whether compounds
      with GABAergic activity are present in milk from camels or other species. We
      determined CMk free-GABA concentration by LS/MS and its bioactivity on human GABA
      receptors. We found that camel and goat milks have significantly more
      bioavailable GABA than cow and human milks and are able to activate GABArho
      receptors. The relationship between GABA and taurine concentrations suggests that
      whole camel milk may be more efficient to activate GABArho1 receptors than goat
      milk. Because GABArho receptors are normally found in enteroendocrine cells in
      the lumen of the digestive tract, these results suggest that GABA in camel and
      goat milk may participate in GABA-modulated functions of enteroendocrine cells in
      the GI lumen. 

PMID- 24128505
TI  - Aroma quality assessment of Korean fermented red pepper paste (gochujang) by
      aroma extract dilution analysis and headspace solid-phase microextraction-gas
      chromatography-olfactometry.
AB  - The objective of this study was to assess aroma quality of gochujang using purge
      and trap, simultaneous steam distillation and solvent extraction (SDE), and
      headspace solid-phase microextraction (HS-SPME), followed by gas chromatography
      olfactometry (GC-O). Nineteen and 28 aroma-active compounds were detected by
      aroma extract dilution analysis of purge and trap and SDE, respectively. Diallyl
      disulfide and 3-isobutyl-2-methoxypyrazine played a significant role in the aroma
      quality of gochujang. Twelve aroma-active compounds were detected by HS-SPME-GC-O
      based on sample dilution analysis. Methional, diallyl disulfide, and 3-isobutyl-2
      methoxypyrazine were the most intense aroma-active compounds. 3-Isobutyl-2
      methoxypyrazine was identified for the first time in gochujang. 

PMID- 24128506
TI  - Characterisation of metabolic profile of banana genotypes, aiming at biofortified
      Musa spp. cultivars.
AB  - The banana is an important, widely consumed fruit, especially in areas of rampant
      undernutrition. Twenty-nine samples were analysed, including 9 diploids, 13
      triploids and 7 tetraploids, in the Active Germplasm Bank, at Embrapa Cassava &
      Fruits, to evaluate the bioactive compounds. The results of this study reveal the
      presence of a diversity of bioactive compounds, e.g., catechins; they are
      phenolic compounds with high antioxidant potential and antitumour activity. In
      addition, accessions with appreciable amounts of pVACs were identified,
      especially compared with the main cultivars that are currently marketed. The ATR
      FTIR, combined with principal components analysis, identified accessions with
      distinct metabolic profiles in the fingerprint regions of compounds important for
      human health. Likewise, starch fraction characterisation allowed discrimination
      of accessions according to their physical, chemical, and functional properties.
      The results of this study demonstrate that the banana has functional
      characteristics endowing it with the potential to promote human health. 

PMID- 24128507
TI  - Effects of heating, aerial exposure and illumination on stability of fucoxanthin
      in canola oil.
AB  - The effects of heating, aerial exposure and illumination on the stability of
      fucoxanthin was investigated in canola oil. In the absence of air and light, the
      heating caused the degradation of total and all-trans fucoxanthin at all tested
      temperatures between 25 and 100  degrees C. The increase of heating temperature
      promoted the formation of 13-cis and 13'-cis and the degradation of 9'-cis. The
      degradation and formation reactions were found to follow simple first-order
      kinetics and to be energetically unfavorable, non-spontaneous processes.
      Arrhenius-type temperature dependence was observed for the degradation of total
      and all-trans fucoxanthin but not for the reactions of cis isomers. The aerial
      exposure promoted the oxidative fucoxanthin degradation at 25  degrees C, whilst
      illumination caused the initial formation of all-trans, with concurrent sudden
      degradation of 13-cis and 13'-cis, and the considerable formation of 9'-cis. The
      fucoxanthin degradation was synergistically promoted when exposed to both air and
      light.

PMID- 24128509
TI  - Isolation by pressurised fluid extraction (PFE) and identification using CPC and
      HPLC/ESI/MS of phenolic compounds from Brazilian cherry seeds (Eugenia uniflora
      L.).
AB  - Brazilian cherry seeds are a waste product from juice and frozen pulp production
      and, the seeds composition was investigated to valorize this by-product.
      Compounds separation was performed with ethanol by pressurised fluid extraction
      (PFE). Here we determine the effect of temperature (T), static time (ST), number
      of cycles (C), and flush volume (VF) on the yield, composition and total phenolic
      content (TPC) of the seed extracts. T, ST and their interaction positively
      influenced yield and TPC. Extracts were fractionated by high performance liquid
      chromatography (HPLC) and centrifugal partition chromatography (CPC). The
      collected fractions characterizations were made by electrospray ionisation mass
      spectrometry (ESI/MS) and high resolution mass spectrometry (HRMS) indicated the
      presence of ellagic acid pentoside and deoxyhexose, quercitrin and kaempferol
      pentoside. All of these compounds have antioxidant properties and normally are
      found in plant extracts. These results confirm that Brazilian cherry seed extract
      is a potentially valuable source of antioxidants. 

PMID- 24128508
TI  - Effect of different types of sugars in a marinating formulation on the formation
      of heterocyclic amines in grilled chicken.
AB  - The aim of the study was to determine the effect of different types of sugar on
      the formation of heterocyclic amines (HCA) in marinated grilled chicken. Chicken
      breast samples were marinated with table sugar, brown sugar, and honey for 24h at
      4  degrees C. The internal temperature, weight loss, free amino acids, sugars,
      and HCA were determined. The concentrations of all types of HCA (except IQx) in
      samples that were marinated with table sugar were significantly higher (p<0.006)
      than brown sugar; whereas those were marinated with honey had the lowest HCA
      concentrations. A substantial reduction in the concentration of MeIQ, PhIP,
      DiMeIQx, IQ, IQx, and norharman was achieved in chicken marinated with honey. A
      correlation study indicated that adding honey into the recipe retarded the
      formation of most HCA (MeIQ, DiMeIQx, IQ, IQx, norharman, and harman), whereas
      table sugars enhanced the formation of all HCA except norharman, harman, and
      AalphaC. 

PMID- 24128510
TI  - Detection of pork adulteration by highly-specific PCR assay of mitochondrial D
      loop.
AB  - We describe a highly specific PCR assay for the authentic identification of pork.
      Accurate detection of tissues derived from pig (Sus scrofa) was accomplished by
      using newly designed primers targeting porcine mitochondrial displacement (D
      loop) region that yielded an unique amplicon of 712 base pairs (bp). Possibility
      of cross-amplification was precluded by testing as many as 24 animal species
      (mammals, birds, rodent and fish). Suitability of PCR assay was confirmed in raw
      (n = 20), cooked (60, 80 and 100  degrees C), autoclaved (121  degrees C) and
      micro-oven processed pork. Sensitivity of detection of pork in other species meat
      using unique pig-specific PCR was established to be at 0.1%; limit of detection
      (LOD) of pig DNA was 10 pg (pico grams). The technique can be used for the
      authentication of raw, processed and adulterated pork and products under the
      circumstances of food adulteration related disputes or forensic detection of
      origin of pig species.

PMID- 24128511
TI  - Effect of 10 MeV E-beam irradiation combined with vacuum-packaging on the shelf
      life of Atlantic salmon fillets during storage at 4  degrees C.
AB  - Biochemical properties and gel-forming ability were investigated as a function of
      storage time to understand the effect of 10 MeV electron linear accelerator
      irradiation, combined with vacuum-packaging changes, on Atlantic salmon fillets
      during cold storage at 4  degrees C. The results showed that compared with those
      of the control samples, pH, water soluble protein and extractable protein were
      not significantly altered by irradiation. However, pH, water soluble protein and
      extractable protein changed notably as storage time increased. While salt soluble
      protein (SSP), total volatile base nitrogen (TVB-N), a(*) values, 2
      thiobarbituric acid (TBA) and total viable counts (TVC) were significantly
      (p<0.05) affected by different irradiation doses, which inhibited the increase in
      TVB-N but promoted TBA values during the storage period. Moreover, irradiation up
      to 3 kGy did not significantly change the gel patterns, while the MHC patterns
      were slightly reduced with the increasing of the storage time.

PMID- 24128512
TI  - One-step column chromatographic extraction with gradient elution followed by
      automatic separation of volatiles, flavonoids and polysaccharides from Citrus
      grandis.
AB  - Citrus grandis Tomentosa is widely used in traditional Chinese medicine and
      health foods. Its functional components include volatiles, flavonoids and
      polysaccharides which cannot be effectively extracted through traditional
      methods. A column chromatographic extraction with gradient elution was developed
      for one-step extraction of all bioactive substances from C. grandis. Dried
      material was loaded into a column with petroleum ether: ethanol (8:2, PE) and
      sequentially eluted with 2-fold PE, 3-fold ethanol: water (6:4) and 8-fold water.
      The elutes was separated into an ether fraction containing volatiles and an
      ethanol-water fraction containing flavonoids and polysaccharides. The later was
      separated into flavonoids and polysaccharides by 80% ethanol precipitation of
      polysaccharides. Through this procedure, volatiles, flavonoids and
      polysaccharides in C. grandis were simultaneously extracted at 98% extraction
      rates and simply separated at higher than 95% recovery rates. The method provides
      a simple and high-efficient extraction and separation of wide range bioactive
      substances. 

PMID- 24128513
TI  - Determination of pork spoilage by colorimetric gas sensor array based on natural
      pigments.
AB  - A new colorimetric gas-sensor array based on four natural pigments, that were
      extracted from spinach (Spinacia oleracea), red radish (Raphanus sativus L.),
      winter jasmine (Jasminum nudiflorum), and black rice (Oryza sativa L. indica),
      was developed for pork freshness evaluation. A colour change profile for each
      sample was obtained by differentiating the images of the sensor array before and
      after exposure to the odour of sample. The total viable count (TVC) per gram of
      pork was obtained by classical microbiological plating methods, and the biogenic
      amines were measured by HPLC. Biogenic amine index (BAI) for the determination of
      meat freshness was developed from the sum of putrescine and cadaverine. The
      colour change profiles were analysed using principal component analysis and
      correlated with conventional methods (BAI, TVC). A partial least squares (PLS)
      prediction model was obtained with r=0.854 and 0.933 for BAI and TVC,
      respectively. 

PMID- 24128514
TI  - Determination of 5,7-dihydroxychromone and luteolin in peanut hulls by capillary
      electrophoresis with a multiwall carbon nanotube/poly(ethylene terephthalate)
      composite electrode.
AB  - A novel multiwall carbon nanotube/poly(ethylene terephthalate) (MWCNT/PET)
      composite electrode was developed for the determination of 5,7-dihydroxychromone
      and luteolin in peanut hulls in combination with capillary electrophoresis (CE).
      The electrode was fabricated by packing a mixture of MWCNTs and melted PET in a
      piece of fused-silica capillary under heat. Because of the simple composition of
      the phenolic constituents in peanut hulls, they were used to demonstrate the
      performance of the fabricated electrode. The results indicated that 5,7
      dihydroxychromone and luteolin were well separated within 12 min in a 40 cm long
      capillary at a separation voltage of 12 kV using a 50mM borate buffer (pH 9.2).
      The MWCNT-based electrode exhibited significantly lower detection potentials,
      enhanced signal-to-noise characteristics, and higher resistance to surface
      fouling compared to graphite/PET composite electrode. It showed long-term
      stability and reproducibility with a relative standard deviation of 2.6% for the
      peak current (n = 15). The relation between peak current and analyte
      concentration was linear over about three orders of magnitude. The proposed
      method has been applied to determine the two bioactive constituents in real
      samples.

PMID- 24128515
TI  - The relationship between size and lipid composition of the bovine milk fat
      globule is modulated by lactation stage.
AB  - The effect of lactation stage and size on the lipid composition of bovine milk
      fat globules (MFG) and their membranes (MFGM) was investigated. MFG were
      separated into six size groups (1-3 MUm) from samples collected in early, mid and
      late lactation stages (10-250 days postpartum). Fatty acid and polar lipid
      composition was determined in each size group, at each lactation stage. PUFA
      concentration was affected by lactation stage but not MFG size. Saturated fatty
      acid concentration at 60 days postpartum was 10% higher in small vs. large
      globules. Phosphatidylcholine and cholesterol followed the same concentration
      pattern throughout lactation in all MFG size groups. From day 100 postpartum on,
      phosphatidylethanolamine concentration was constant in the large MFG, but dropped
      twofold in the small MFG. Results suggest distinct compositional regulation for
      large and small MFG at different lactation stages. Such interactions between
      structure, composition and lactation stage may be exploited for human milk and
      dairy product consumption.

PMID- 24128516
TI  - Synthesis and characterisation of nano-pore antimony imprinted polymer and its
      use in the extraction and determination of antimony in water and fruit juice
      samples.
AB  - A solid phase extraction method using antimony ion imprinted polymer (IIP)
      sorbent combined with electrothermal atomic absorption spectrometry (ETAAS) was
      developed for the extraction and speciation of antimony. The sorbent has been
      synthesised in the presence of Sb(III) and ammonium pyrrolidine dithiocarbamate
      (APDC) using styrene as the monomer and ethylene glycol dimethacrylate (EGDMA) as
      the cross linker. The imprinted Sb(III) ions were removed by leaching with HCl
      (50%v/v) and the polymer was characterised by FT-IR and scanning electron
      microscopy. The maximum sorption capacity of the IIP for Sb(III) ions was found
      to be 6.7 mg g(-1). With preconcentration of 60 mL of sample, an enhancement
      factor of 232 and detection limit of 3.9 ng L(-1) was obtained. Total antimony
      was determined after the reduction of Sb(V) to Sb(III). The method was
      successfully applied to the determination of antimony species in water samples
      and total antimony in fruit juices.

PMID- 24128517
TI  - Phytochemical content and antioxidant properties of diverse varieties of whole
      barley (Hordeum vulgare L.) grown in Tunisia.
AB  - Four varieties (Rihane, Manel, Roho, and Tej) of Tunisian barley were analysed
      for their antioxidant activities (AA) using ABTS and DPPH radicals cation, and
      ferric reducing/antioxidant power (FRAP) methods. The total phenolic (TPC), total
      flavonoid (TFC) and condensed tannins (CTC) contents were measured. The results
      indicated that the total phenolic contents ranged from 195.02 +/- 0.32 to 220.11
      +/- 0.32 mg gallic acid equivalent/100g fresh weight. Results showed that Rihane
      has the highest TPC, TFC and CTC compared to other varieties. Roho barley had a
      lower activity than Tej barley. A significant correlation (p<0.05) was found
      between TPC, TFC, CTC and AA. This study suggests that Tunisian barley varieties
      may serve as a good source of natural antioxidants.

PMID- 24128518
TI  - Blends of olive oil and seeds oils: characterisation and olive oil quantification
      using fatty acids composition and chemometric tools. Part II.
AB  - A method to verify the percentage of olive oil in a blend, in compliance with the
      Commission Regulation EU No. 29/2012, was developed by GC-FID analysis of methyl
      esters of fatty acids, followed by chemometric tools (PCA, TFA, SIMCA and PLS).
      First of all, binary blends of twelve olive oils and one sunflower oil were
      studied, in order to evaluate the variability associated to the fatty acids
      profile of olive oils (Monfreda, Gobbi, & Grippa, 2012). In this study, binary
      blends of twelve olive oils with four types of seeds oils (peanut, corn, rice and
      grape seed oils) were evaluated. These four groups of blends were analysed and
      processed separately, each group consisting of 36 samples with 40%, 50% and 60%
      of olive oil content. Chemometric tools were also applied to the global data set
      (180 samples, including those analysed in the previous paper). Outstanding
      results were achieved, showing that the proposed method would be capable to
      discriminate blends with a difference in concentration of olive oil lower than 5%
      (a standard error of prediction of 3.97% was obtained with PLS). Therefore blends
      containing 45% and 55% of olive oil were also analysed with the current method
      and added to the data sets for chemometric assessment with supervised tools.
      SIMCA still provided good models; however the best performance was achieved by
      processing each group of binary blends (consisting of 60 samples) separately,
      rather than applying SIMCA to the overall data set (300 samples). On the other
      hand PLS did not show significant improvements. 

PMID- 24128519
TI  - Performance evaluation of commercial ELISA kits for screening of furazolidone and
      furaltadone residues in fish.
AB  - Regulatory monitoring for nitrofuran drug residues in aquaculture products has
      largely focused on LC-MS/MS. In addition, there is a need for facile and high
      throughput screening methods for monitoring programs. We evaluated the
      performance of Ridascreen (R-Biopharm) ELISA kits for nitrofuran drug residues in
      fish muscle, with verification by LC-MS/MS. Kits were available for 3-amino-2
      oxazolidinone (AOZ) and 3-amino-5-morpholino-methyl-2-oxazolidinone (AMOZ) side
      chains of furazolidone and furaltadone, respectively. We found good repeatability
      in fortified and incurred muscle samples, with RSDs ranging from 1.8% to 7.6%.
      Recoveries of AOZ and AMOZ from muscle fortified at levels of 0.5-2 ng/g ranged
      from 98% to 114%. Excellent selectivity was demonstrated. The minimum detection
      limits (MDLs) for AOZ and AMOZ in muscle were 0.05 and 0.2 ng/g, respectively.
      ELISA data were highly correlated with those of LC-MS/MS. Results of this study
      support the use of these kits as screening assays for nitrofuran residues in fish
      muscle.

PMID- 24128520
TI  - Phenolic profile and antioxidant activity of Serbian polyfloral honeys.
AB  - A total of 58 polyfloral honey samples from different regions in Serbia were
      studied to determine their phenolic profile, total phenolic content and
      antioxidant capacity. UHPLC-LTQ OrbiTrap MS made possible the identification of
      36 compounds: 24 flavonoids, two abscisic acids, and 10 phenolic acids and their
      derivatives. Quantification was done using 14 available standards. Data on
      phenolics and abscisic acids allowed the discrimination and classification of
      honeys in accordance to their geographical origin, using pattern recognition
      techniques, principal component analysis and partial least squares discriminant
      analysis. Samples originated from Vojvodina and Zlatibor region were clearly
      distinguished from those from the rest of Serbia because of the presence of
      dicaffeoylquinic acid, ellagic acid, caffeic acid phenethyl ester, and
      chlorogenic acid, among others. A good correlation (r = 0.865) was observed
      between total phenolic content and radical-scavenging activity. Total phenolic
      content ranged from 0.03 to 1.39 mg GAE/g and radical scavenging activity ranged
      from 1.31% to 25.61%.

PMID- 24128521
TI  - Maillard reaction products as antimicrobial components for packaging films.
AB  - Active packaging foils with incorporated antimicrobial agents release the active
      ingredient during food storage. Maillard reaction products (MRPs) show
      antimicrobial activity that is at least partially mediated by H2O2. De novo
      generation of H2O2 by an MRP fraction, extracted from a ribose/lysine Maillard
      reaction mixture by 85% ethanol, was monitored at three concentrations (1.6,
      16.1, and 32.3g/L) and three temperatures (4, 25, and 37  degrees C) between 0
      and 96 h, reaching a maximum of 335 MUM H2O2 (32.3g/L, 37  degrees C, 96 h). The
      active MRP fraction (16.1g/L) completely inhibited the growth of Escherichia coli
      for 24h and was therefore incorporated in a polyvinyl acetate-based lacquer and
      dispersed onto a low-density polyethylene film. The coated film generated about
      100 MUM H2O2 and resulted in a log-reduction of >5 log-cycles against E. coli.
      Thus, MRPs can be considered as active ingredients for antimicrobial packaging
      materials.

PMID- 24128522
TI  - Biocomponent determination in vinegars with the help of 14C measured by liquid
      scintillation counting.
AB  - This article presents a method of carbon extraction from vinegar used in
      preparation of liquid scintillation counting cocktails for measurements of low
      (14)C radioactivity. The presented method is relatively fast and can be used to
      produce liquid scintillation cocktails e.g., via benzene synthesis. In this work
      we present specific radiocarbon radioactivity determinations and based on them
      estimation of bio product content for five commercially available vinegars. All
      investigated vinegars are likely produced from plants in fermentation process. 

PMID- 24128523
TI  - Electrochemical determination of toxic ractopamine at an ordered mesoporous
      carbon modified electrode.
AB  - A sensitive electrochemical sensor was developed to detect toxic ractopamine
      using ordered mesoporus carbon (OMC) modified glass carbon electrode (OMC/GCE).
      Cyclic voltammetry was used to investigate the electrochemical behaviours of
      ractopamine on OMC/GCE. The results indicated that the OMC modified electrode can
      remarkably enhance electrocatalytic activity towards the oxidation of ractopamine
      with a great increase of peak current. The oxidation mechanism was studied and
      the results showed that the oxidation of ractopamine involved two protons and two
      electrons of its two phenolic hydroxyl groups. The signal for the determination
      of ractopamine was recorded using differential pulse voltammetry (DPV) and the
      optimisation for the experimental conditions was also conducted. The results
      showed that the response of the sensor to concentration of ractopamine displayed
      a linear correlation over a range from 0.085 MUM to 8.0 MUM with a detection
      limit of 0.06 MUM, demonstrating favourable sensitivity and selectivity for the
      detection of ractopamine. Finally, the method was successfully applied for the
      determination of ractopamine in pork samples with satisfying recoveries in the
      range of 96.6-104.5% and excellent RSD of less than 5%.

PMID- 24128524
TI  - An application of wavelet moments to the similarity analysis of three-dimensional
      fingerprint spectra obtained by high-performance liquid chromatography coupled
      with diode array detector.
AB  - More and more the three-dimensional (3D) fingerprint spectra, which can be
      obtained by high performance liquid chromatography coupled with diode array
      detector (HPLC-DAD), are applied to the analysis of drugs and foods. A novel
      approach to the similarity analysis of traditional Chinese medicines (TCMs) was
      proposed based on the digital image processing using 3D HPLC-DAD fingerprint
      spectra. As the one of shape features of digital grayscale image, wavelet moments
      were employed to extract the shape features from the grayscale images of 3D
      fingerprint spectra of different Coptis chinensis samples, and used to the
      similarity analysis of these samples. Compared with the results obtained by
      traditional features including principal components and spectrum data under
      single-wavelength, our results represented the more reliable assessment. This
      work indicates that the better features of fingerprint spectra are more important
      than similarity evaluation methods. Wavelet moments, which possess multi
      resolution specialty and the invariance property in image processing, are more
      effective than traditional spectral features for the description of the systemic
      characterisation of mixture sample. 

PMID- 24128525
TI  - Purification and characterization of a gelatinolytic matrix metalloproteinase
      from the skeletal muscle of grass carp (Ctenopharyngodon idellus).
AB  - A gelatinolytic matrix metalloproteinase (gMMP) from grass carp skeletal muscle
      was purified by 30-70% ammonium sulphate fractionation and a combination of
      chromatographic steps including ion exchange on DEAE-Sephacel, gel filtration on
      Sephacryl S-200, and affinity on gelatin-sepharose. The molecular weight of the
      proteinase as estimated by SDS-PAGE was 70 kDa under non-reducing conditions. The
      enzyme revealed high activity from 30 to 50  degrees C, and the gelatin
      hydrolysing activity was investigated at a slightly alkaline pH range using
      gelatin as substrate. Metalloproteinase inhibitor EDTA completely suppressed the
      gelatinolytic activity, while other proteinase inhibitors did not show any
      inhibitory effect. Divalent metal ion Ca(2+) was essential for the gelatinolytic
      activity. Further, peptide mass fingerprinting obtained four fragments with 45
      amino acid residues, which were highly identical to MMP-2 from fish species. The
      gMMP could effectively hydrolyse type I collagen even at 4  degrees C, suggesting
      its involvement in the texture softening of fish muscle during the post-mortem
      stage.

PMID- 24128526
TI  - Discrimination of Chinese green tea according to varieties and grade levels using
      artificial nose and tongue based on colorimetric sensor arrays.
AB  - Colorimetric artificial tongue and nose were used to discriminate nine Chinese
      green teas from different geographical origins and grade levels. Printing
      nanoporous porphyrin, dimeric metalloporphyrins, metallosalophen complexes and
      chemically responsive dyes on a hydrophobic membrane, the developed sensor array
      of artificial tongue and nose showed a unique pattern of colorimetric change upon
      exposure to green tea liquids or gases. All green tea samples, both in liquid and
      gas analysis, gave distinct patterns according to geographical origin and grade
      level, thus resulting in their facile identification. The good reproducibility of
      colorimetric artificial tongue and nose was proved. Data analysis was performed
      by chemometric techniques: hierarchical cluster analysis (HCA), and principal
      component analysis (PCA). Chinese green tea from the same geographical origin
      could cluster together in PCA score plot. No errors in classification by HCA were
      observed in 90 trials. The colorimetric artificial tongue and nose can be used to
      discriminate Chinese green tea according to geographical origin and grade level. 

PMID- 24128527
TI  - Increased stability and protease resistance of the beta-lactoglobulin/vitamin D3
      complex.
AB  - The stability of the beta-lactoglobulin (betalg)/vitamin D3 (D3) complex at 4
      degrees C and upon exposure to UV-C light, and in simulated intestinal fluid,
      were studied in vitro. Caco-2 cells were used to demonstrate the passage of the
      betalg/D3 complex across the monolayers. Furthermore, an in vivo experiment was
      conducted by force-feeding rats with the free D3 and betalg/D3 complex, with
      subsequent determination of the plasma concentration of 25-hydroxy-D3. The
      betalg/D3 complex significantly improved the stability of the vitamin at 4 
      degrees C and when exposed to UV-C light. The resistance of betalg to proteases
      was increased, indicating a mutual protective effect. The betalg/D3 complex
      crossed the monolayers, which was confirmed by the significant increase in the
      concentration of 25-hydroxy-D3 in rats fed the betalg/D3 complex compared to the
      ones fed the free D3. Therefore, the current study suggests that the betalg/D3
      complex can effectively be used for the fortification of milk products and low
      fat content foods to improve the intake and bioavailability of D3.

PMID- 24128528
TI  - Evaluation of volatile metabolites as markers in Lycopersicon esculentum L.
      cultivars discrimination by multivariate analysis of headspace solid phase
      microextraction and mass spectrometry data.
AB  - To gain insights on the effects of cultivar on the volatile metabolomic
      expression of different tomato (Lycopersicon esculentum L.) cultivars--Plum,
      Campari, Grape, Cherry and Regional, cultivated under similar edafoclimatic
      conditions, and to identify the most discriminate volatile marker metabolites
      related to the cultivar, the chromatographic profiles resulting from headspace
      solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry
      (GC-qMS) analysis, combined with multivariate analysis were investigated. The
      data set composed by the 77 volatile metabolites identified in the target tomato
      cultivars, 5 of which (2,2,6-trimethylcyclohexanone, 2-methyl-6-methyleneoctan-2
      ol, 4-octadecyl-morpholine, (Z)-methyl-3-hexenoate and 3-octanone) are reported
      for the first time in tomato volatile metabolomic composition, was evaluated by
      chemometrics. Firstly, principal component analysis was carried out in order to
      visualise data trends and clusters, and then, linear discriminant analysis in
      order to detect the set of volatile metabolites able to differentiate groups
      according to tomato cultivars. The results obtained revealed a perfect
      discrimination between the different Lycopersicon esculentum L. cultivars
      considered. The assignment success rate was 100% in classification and 80% in
      prediction ability by using "leave-one-out" cross-validation procedure. The
      volatile profile was able to differentiate all five cultivars and revealed
      complex interactions between them including the participation in the same
      biosynthetic pathway. The volatile metabolomic platform for tomato samples
      obtained by HS-SPME/GC-qMS here described, and the interrelationship detected
      among the volatile metabolites can be used as a roadmap for biotechnological
      applications, namely to improve tomato aroma and their acceptance in the final
      consumer, and for traceability studies.

PMID- 24128529
TI  - Coordinate changes in gene expression and triacylglycerol composition in the
      developing seeds of oilseed rape (Brassica napus) and turnip rape (Brassica
      rapa).
AB  - Crop production for vegetable oil in the northern latitudes utilises oilseed rape
      (Brassica napus subsp. oleifera) and turnip rape (B. rapa subsp. oleifera),
      having similar oil compositions. The oil consists mostly of triacylglycerols,
      which are synthesised during seed development. In this study, we characterised
      the oil composition and the expression levels of genes involved in
      triacylglycerol biosynthesis in the developing seeds in optimal, low temperature
      (15  degrees C) and short day (12-h day length) conditions. Gene expression
      levels of several genes were altered during seed development. Low temperature and
      short day treatments increased the level of 9,12,15-octadecatrienoic acid (18:3n
      3) in turnip rape and short day treatment decreased the total oil content in both
      species. This study gives a novel view on seed oil biosynthesis under different
      growth conditions, bringing together gene expression levels of the
      triacylglycerol biosynthesis pathway and oil composition over a time series in
      two related oilseed species.

PMID- 24128530
TI  - Phenolic compositions and antioxidant capacities of Chinese wild mandarin (Citrus
      reticulata Blanco) fruits.
AB  - As one of the most important centres of origin for the genus Citrus L., China is
      rich in wild mandarin germplasm. In this study, phenolic compounds in the peels
      of 14 wild mandarin genotypes native to China were determined and their
      antioxidant capacities were evaluated using DPPH, FRAP, ABTS and ORAC methods. We
      found that Nieduyeju had the highest total phenol content (51.14 mg/g DW), and
      Wulongsuanju had the highest total flavonoid content (20.66 mg/g DW). Hesperidin,
      the dominant flavonoid, was observed to be highest in Guangxihongpisuanju (55.98
      mg/g DW). Ferulic acid was the most abundant phenolic acid analyzed, and
      Nieduyeju (7780.17 MUg/g DW) and Guangxihongpisuanju (13,607.19 MUg/g DW) had the
      highest contents of extractable and bound phenolic acid, respectively.
      Antioxidant potency composite (APC) index showed obvious variations ranging from
      58.84 to 98.89 in the studied wild mandarins, among them, Nieduyeju had the
      highest APC index. Overall, Guangxihongpisuanju, Nieduyeju, Cupigoushigan and
      Daoxianyeju contained more phenolics and exhibited higher antioxidant capacities
      than the mandarin cultivars Satsuma and Ponkan.

PMID- 24128531
TI  - Effect of the icing with thyme, oregano and clove extracts on quality parameters
      of gutted and beheaded anchovy (Engraulis encrasicholus) during chilled storage.
AB  - The effect of ice containing thyme (0.04% w/v), oregano (0.03% w/v) and clove
      (0.02% w/v) extracts on the quality parameters of anchovy (Engraulis
      encrasicholus) was assessed through the chemical, sensory and microbiological
      methods. According to sensory analyses, anchovy stored in ice prepared with each
      plant extracts had a shelf life of 12 days, while batch stored in traditional ice
      had a shelf life of 9 days. pH were not significantly affected by the presence of
      plant extracts in the ice. However, a marked antioxidant effect (P<0.05) could be
      detected with fish kept under plant extract icing systems, according to peroxide
      (PV) and thiobarbituric acid (TBA) values. Moreover, the employment of such icing
      systems led to lower (P<0.05) total volatile base-nitrogen (TVB-N) value and free
      fatty acid (FFA) formation. Thus, TVB-N proved to be a suitable index for the
      spoilage of anchovies during chilled storage. The employment of such icing
      systems also led to significantly lower counts of aerobic mesophiles and
      psychrotrophic bacteria in anchovy muscle with skin, as compared with the
      traditional ice batch. This work demonstrates that the use of ice with plant
      extracts for the storage of gutted and beheaded anchovy can be recommended to
      improve the quality and extend the shelf life.

PMID- 24128532
TI  - Novel molecularly imprinted polymers with carbon nanotube as matrix for selective
      solid-phase extraction of emodin from kiwi fruit root.
AB  - In this paper, we present a novel surface imprinting technique for the
      preparation of molecularly imprinted polymers/multi-walled carbon nanotubes
      (MIPs/MWNTs) for extraction of emodin from kiwi fruit root. The MIPs/MWNTs were
      characterised by scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FT-IR). The properties involving adsorption dynamics,
      static adsorption, and selective recognition capacity were evaluated. The
      MIPs/MWNTs exhibited good site accessibility in which it only took 60 min to
      achieve adsorption equilibrium and highly selective recognition for the template
      emodin. Furthermore, the performance of the MIPs/MWNTs as solid phase extraction
      (SPE) material was investigated in detail. The proposed MIPs/MWNTs-SPE procedure
      for emodin exhibited satisfactory recoveries ranging from 89.2% to 93.8% for real
      samples. It was used for the purification and enrichment of emodin from kiwi
      fruit root successfully.

PMID- 24128533
TI  - Attenuation coefficients and absorbed gamma radiation energy of different
      varieties of potato, mango and prawn at different storage time and physiological
      condition.
AB  - Attenuation coefficients of different varieties of gamma irradiated potato (Kufri
      Chandramukhi, Kufri Jyoti, and Kufri Sindhuri), mango (Himsagar, Langra, Dashehri
      and Fazli) and prawn (Tiger prawn and Fresh water prawn) of different storage
      time and physiological stages were determined. After six months storage
      attenuation coefficient of Kufri Chandramukhi was decreased by 30.8% with
      decrease of density and moisture content. Decreasing trend of attenuation
      coefficient during storage was more prominent (almost 50%) in other two varieties
      of potato. On the other hand in all four varieties, unripe mango consisted of
      significantly less (p <= 0.05) attenuation coefficient (around 11-14%) than the
      ripe one due to changes in physiological properties and density. Different
      varieties of prawn had different attenuation coefficients due to subtle
      differences in their proximate composition. Due to having different attenuation
      coefficients, different food components, even different varieties of same food
      component absorbed different gamma radiation energy though exposed to same
      radiation dose.

PMID- 24128534
TI  - Antioxidant properties of 3-deoxyanthocyanidins and polyphenolic extracts from
      Cote d'Ivoire's red and white sorghums assessed by ORAC and in vitro LDL
      oxidisability tests.
AB  - Red sorghum is a source of phenolic compounds (PCs), including 3
      deoxyanthocyanidins that may protect against oxidative stress related disease
      such as atherosclerosis. HPLC was used to characterise and quantify PCs extracted
      from red or white sorghum whole grain flour. Antioxidant activity was measured by
      an oxygen radical absorbance capacity assay and against LDL-oxidisability, and
      further compared to that of synthesised 3-deoxyanthocyanidins (i.e., luteolinidin
      and apigeninidin). Phenolic content of red and white sorghums was evaluated as
      3.90 +/- 0.01 and 0.07 +/- 0.01 mmol gallic acid equivalents L(-1), respectively.
      Luteolinidin and apigeninidin were mainly found in red sorghum. Red sorghum had
      almost 3 and 10 times greater specific antioxidant activity compared to
      luteolinidin and apigeninidin, respectively. Red sorghum PCs and the two 3
      deoxyanthocyanidins were also effective at preventing LDL vitamin E depletion and
      conjugated diene production. Red sorghum flour exhibits antioxidant capacity
      suggesting that it may be a valuable health-promoting food.

PMID- 24128535
TI  - Solid state fermentation of food waste mixtures for single cell protein, aroma
      volatiles and fat production.
AB  - Growth of selected microorganisms of industrial interest (Saccharomyces
      cerevisiae, Kluyveromyces marxianus and kefir) by solid state fermentation (SSF)
      of various food industry waste mixtures was studied. The fermented products were
      analysed for protein, and nutrient minerals content, as well as for aroma
      volatile compounds by GC/MS. The substrate fermented by K. marxianus contained
      the highest sum of fat and protein concentration (59.2% w/w dm) and therefore it
      could be considered for utilisation of its fat content and for livestock feed
      enrichment. Regarding volatiles, the formation of high amounts of epsilon-pinene
      was observed only in the SSF product of kefir at a yield estimated to be 4 kg/tn
      of SSF product. A preliminary design of a biorefinery-type process flow sheet and
      its economic analysis, indicated potential production of products (enriched
      livestock feed, fat and epsilon-pinene) of significant added value.

PMID- 24128536
TI  - Phytochemical changes in phenolics, anthocyanins, ascorbic acid, and carotenoids
      associated with sweetpotato storage and impacts on bioactive properties.
AB  - Sweetpotato phytochemical content was evaluated in four genotypes (NCPUR06-020,
      Covington, Yellow Covington, and NC07-847) at harvest and after curing/storage
      for 4 or 8 months. Curing and storage for up to 8 months did not significantly
      affect total phenolic content in Covington, Yellow Covington, and NC07-847,
      however for NCPUR06-020, a purple-fleshed selection, total phenolic content
      declined mainly due to anthocyanin degradation during storage. Covington had the
      highest carotenoid content at harvest time (281.9 MUg/g DM), followed by NC07-847
      (26.2 MUg/g DM), and after 8 months, total carotenoids had increased by 25% and
      50%, respectively. Antioxidant activity gradually declined during storage, and
      freshly harvested sweetpotatoes also demonstrated higher anti-inflammatory
      capacity as gauged by inhibition of lipopolysaccharide-induced reactive oxygen
      species (ROS) in SH-SY5Y cells. Gradual changes in sweetpotato phytochemical
      content and antioxidant and anti-inflammatory capacity were noted during normal
      long-term storage, but the specific effects were genotype-dependent.

PMID- 24128537
TI  - Effects of emulsion droplet sizes on the crystallisation of milk fat.
AB  - The crystallisation properties of milk fat emulsions containing dairy-based
      ingredients as functions of emulsion droplet size, cooling rate, and emulsifier
      type were investigated using a differential scanning calorimeter (DSC). Anhydrous
      milk fat and its fractions (stearin and olein) were emulsified with whey protein
      concentrate, sodium caseinate, and Tween80 by homogenisation to produce emulsions
      in various size ranges (0.13-3.10 MUm). Particle size, cooling rate, and types of
      emulsifier all had an influence on the crystallisation properties of fat in the
      emulsions. In general, the crystallisation temperature of emulsified fats
      decreased with decreasing average droplet size and was of an exponent function of
      size, indicating that the influence of particle size on crystallisation
      temperature is more pronounced in the sub-micron range. This particle size effect
      was also verified by electron microscopy.

PMID- 24128538
TI  - Evaluation of selenium species in selenium-enriched pakchoi (Brassica chinensis
      Jusl var parachinensis (Bailey) Tsen & Lee) using mixed ion-pair reversed phase
      HPLC-ICP-MS.
AB  - HPLC-ICP-MS based on ion-paired reversed phase chromatography for the selenium
      speciation using the mixture of 1-butanesulfonic acid (BA) and trifluoroacetic
      acid (TFA) as the mixed ion-pairing reagents was developed and applied to
      selenium-enriched pakchoi (Brassica chinensis Jusl var parachinensis (Bailey)
      Tsen & Lee). Several conditions of ion-paired reversed phase HPLC-ICP-MS, such as
      pH of the mobile phase, concentration of ion pairing reagents, types and length
      of analytical column, and flow rate of the mobile phase, were optimised for five
      selenium species; selenate (Se(VI)), Selenite (se(IV)), selenocysteine (SeC), Se
      methylselenocysteine (SeMC) and selenomethionine (SeM). The results showed that
      the optimum conditions for pH, BA and TFA condition, type of separating column
      and flow rate, were 4.5, 8mM, 4mM, C18 (250 mm length * 4.6mm I.D) and 1.2 mL
      min(-1), respectively. These conditions archived separation of the organic
      selenium species. The limits of detection (LOD) and quantitation (LOQ) of each
      selenium species were lower than 5 and 16 ng Se mL(-1), respectively.
      Furthermore, the recoveries of most selenium species were good, except for SeC.
      In this research, selenium-enriched pakchoi was cultivated by supplementing
      inorganic selenium from selenate into sand. The result showed that inorganic
      selenium, SeMC, SeM and several unknown species were found in selenium-enriched
      pakchoi sprouts by using the proposed method. Thereby, the biotransformation of
      selenate in pakchoi was similar to other Brassicaceae plants such as kale and
      broccoli.

PMID- 24128539
TI  - Comparing sugar components of cereal and pseudocereal flour by GC-MS analysis.
AB  - Gas chromatography with mass spectrometry was used for carrying out a qualitative
      analysis of the ethanol soluble flour extract of different types of cereals bread
      wheat and spelt and pseudocereals (amaranth and buckwheat). TMSI
      (trimethylsilylimidazole) was used as a reagent for the derivatisation of
      carbohydrates into trimethylsilyl ethers. All samples were first defatted with
      hexane. (In our earlier investigations, hexane extracts were used for the
      analysis of fatty acid of lipid components.) Many components of pentoses, hexoses
      and disaccharides were identified using 73 and 217 Da mass and the Wiley Online
      Library search. The aim of this paper is not to identify and find new components,
      but to compare sugar components of tested samples of flour of cereals bread wheat
      and spelt and pseudocereals (amarnath and buckwheat). Results were analysed using
      descriptive statistics (dendrograms and PCA). The results show that this method
      can be used for making a distinction among different types of flour.

PMID- 24128540
TI  - Affinity adsorption of lysozyme with Reactive Red 120 modified magnetic chitosan
      microspheres.
AB  - Reactive Red 120 was utilized as an affinity dye-ligand to modify the surface of
      magnetic chitosan microspheres to improve the adsorption capacity for lysozyme.
      The impact of pH, ionic strength, adsorption time and initial lysozyme
      concentration on the adsorption of lysozyme from aqueous solutions was
      investigated. An increased adsorption amount of 116.9 mg/g lysozyme on Reactive
      Red 120 modified microspheres was achieved in comparison to 24.6 mg/g on
      unmodified magnetic chitosan microspheres. The adsorption behaviour of lysozyme
      by the Reactive Red 120 modified magnetic chitosan microspheres fitted the pseudo
      second-order kinetic and the Langmuir thermodynamic model. The desorption ratio
      was 92.6% using 1M NaCl phosphate buffer (pH 6.0) as the desorption agent. The
      adsorption capacity of the Reactive Red 120 modified magnetic chitosan
      microspheres did not decrease significantly after four adsorption-desorption
      cycles (P>0.05). The as-prepared Reactive Red 120 modified magnetic chitosan
      microspheres were then used for the extraction of lysozyme from egg white
      solutions. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      results showed that the purity of the obtained lysozyme was ~80.7% and that the
      recovery yield was ~89.1%.

PMID- 24128541
TI  - Physicochemical differences between sorghum starch and sorghum flour modified by
      heat-moisture treatment.
AB  - Sorghum starch and sorghum flour were modified by heat-moisture treatment (HMT)
      at two different moisture contents, 20% and 25%. The result showed that
      solubility and swelling power of modified samples decreased. In addition, the
      pasting viscosities of most modified samples were lower than that of native
      samples. The onset, peak and conclusion temperatures of gelatinization, and the
      enthalpy of samples modified by HMT increased. The crystallinity of the modified
      samples was higher than that of control samples. HMT had a far greater effect on
      the solubility, swelling power, setback viscosity, through viscosity, enthalpy
      and crystallinity of sorghum flour than of sorghum starch. On the granules
      surface there were more holes for the HMT starches than for HMT flours. The
      microstructure of HMT sorghum starch gel had a more orderly and smaller holey
      structure. The sorghum flour gel had originally a crackled structure, but after
      the HMT treatment, it had many ordered and small holes. 

PMID- 24128542
TI  - Improving halva quality with dietary fibres of sesame seed coats and date pulp,
      enriched with emulsifier.
AB  - Supplementation of halva with waste products of manufacturing, for example
      defatted sesame seed coats (testae) and date fibre concentrate, can improve its
      nutritional and organoleptic qualities. These constituents provide high fibre
      content and technological potential for retaining water and fat. Standard halva
      supplemented with date fibre concentrate, defatted sesame testae and emulsifier
      was evaluated for oil separation, texture and colour changes, sensory qualities
      and acceptability to a taste panel. Addition of both fibres with an emulsifier,
      improved emulsion stability and increased the hardness of halva significantly.
      The functional properties of sesame testae and date fibres promote nutrition and
      health, supplying polyphenol antioxidants and laxative benefits. 

PMID- 24128543
TI  - Effect of sugar composition on the water sorption and softening properties of
      cookie.
AB  - In order to elucidate the effect of sugar composition on the water sorption and
      softening properties of cookie, three types of sugar composition (sugar alone,
      sugar-trehalose, and sugar-sorbitol) were employed as an ingredient of cookie,
      and softening temperature (Ts) of the cookie samples, adjusted to various water
      contents, was investigated using thermal rheological analysis. Ts decreased
      linearly with increasing water content of the cookie samples. At each water
      content, Ts of samples was higher in the order of sugar-trehalose>sugaralone
      >sugar-sorbitol. On the other hand, the glass transition temperature (Tg) of the
      sugar and/or sugar alcohol mixtures used for cookie preparation was investigated
      using differential scanning calorimetry. A linear relationship was found between
      anhydrous Ts of the cookie samples and anhydrous Tg of the sugar and/or sugar
      alcohol mixtures. These results suggest that sugar composition plays an important
      role in the softening properties of cookie samples. 

PMID- 24128544
TI  - Changes in antioxidant activity and phenolic acid composition of tarhana with
      steel-cut oats.
AB  - Steel-cut oats (SCO) was used to replace wheat flour in the tarhana formulation
      (control) at the levels of 10%, 20%, 30% and 40% (w/w). Control sample included
      no SCO. Substitution of wheat flour in tarhana formulation with SCO affected the
      mineral contents positively. SCO additions also increased phenolic acid contents
      of tarhana samples. The most abundant phenolic acids were ferulic and vanillic
      acids, followed by syringic acid in the samples with SCO. Tarhana samples with
      SCO also showed higher antioxidant activities than the control. Compared with the
      control, the total phenolic content increased when the level of SCO addition was
      increased. SCO addition did not have a deteriorative effect on sensory properties
      of tarhana samples and resulted in acceptable soup properties in terms of overall
      acceptability. SCO addition improved the nutritional and functional properties of
      tarhana by causing increases in antioxidant activity, phenolic content and
      phenolic acids. 

PMID- 24128545
TI  - Simultaneous separation and determination of fructose, sorbitol, glucose and
      sucrose in fruits by HPLC-ELSD.
AB  - A high-performance liquid chromatography (HPLC) method with evaporative light
      scattering detection (ELSD) was optimised for simultaneous determination of
      fructose, sorbitol, glucose and sucrose in fruits. The analysis was carried out
      on a Phenomenex Luna 5u NH2 100A column (250 mm * 4.60mm, 5 micron) with
      isocratic elution of acetonitrile:water (82.5:17.5, v/v). Drift tube temperature
      of the ELSD system was set to 82  degrees C and nitrogen flow rate was 2.0 L min
      1. The regression equation revealed good linear relationship (R = 0.9967-0.9989)
      within test ranges. The limits of detection (LOD) and quantification (LOQ) for
      four analytes (peach, apple, watermelon, and cherry fruits) were in the range of
      0.07-0.27 and 0.22-0.91 mg L-1, respectively. The proposed HPLC-ELSD method was
      validated for quantification of sugars in peach, apple, watermelon, and cherry
      fruits, and the results were satisfactory. The results showed that the contents
      of the four sugars varied among fruits. While fructose (5.79-104.01 mg g-1) and
      glucose (9.25-99.62 mg g-1) emerged as common sugars in the four fruits, sorbitol
      (8.70-19.13 mg g-1) were only found in peach, apple and cherry fruits, and
      sucrose (15.82-106.39 mg g-1) were in peach, apple and watermelon. There was not
      detectable sorbitol in watermelon and sucrose in cherry fruits, respectively.

PMID- 24128546
TI  - Combined microextraction by packed sorbent and high-performance liquid
      chromatography-ultraviolet detection for rapid analysis of ractopamine in porcine
      muscle and urine samples.
AB  - A method for rapid analysis of ractopamine in porcine muscle and urine was
      developed and validated. The method was based on combined of microextraction by
      packed sorbent (MEPS) and high-performance liquid chromatography with ultraviolet
      detection (HPLC-UV). Parameters of the MEPS procedure affecting extraction
      efficiency were optimised. Optimum extraction conditions were 100 MUL of sample
      in five extraction cycles and sampling time of <3 min. Compared with solid-phase
      extraction, the MEPS procedure required less extraction time, sample volume and
      consumption of organic solvents. The method demonstrated high linearity within
      0.01-2 MUg/mL for porcine muscle and urine samples (R2>0.9985). Accuracies of
      muscle and urine analyses were 93.9-109.2% and 93.4-105.1%, respectively. Intra
      day and inter-day precisions (RSD%) were lower than 11.8% for both analyses. The
      method was applied for rapid analysis of ractopamine in biological samples. The
      method was simpler and could be used to screen other beta2-agonists in other
      extraction media.

PMID- 24128547
TI  - Synthesis and evaluation of odour-active methionyl esters of fatty acids via
      esterification and transesterification of butter oil.
AB  - Methionol-derived fatty acid esters were synthesised by both chemical and lipase
      catalysed esterification between fatty acids and methionol. Beneficial effects of
      both methods were compared qualitatively and quantitatively by GC-MS/GC-FID
      results. And the high acid and heat stability of our designed methionyl esters
      meet the requirement of the food industry. Most importantly, the sensory test
      showed that fatty acid carbon-chain length had an important effect on the flavour
      attributes of methionyl esters. Moreover, through Lipozyme TL IM-mediated
      transesterification, valuable methionol-derived esters were synthesised from the
      readily available natural material butter oil as the fatty acid source. The
      conversion of methionol and yield of each methionyl ester were also elucidated by
      GC-MS-FID. 

PMID- 24128548
TI  - Chilean flour and wheat grain: tracing their origin using near infrared
      spectroscopy and chemometrics.
AB  - Instrumental techniques such a near-infrared spectroscopy (NIRS) are used in
      industry to monitor and establish product composition and quality. As occurs with
      other food industries, the Chilean flour industry needs simple, rapid techniques
      to objectively assess the origin of different products, which is often related to
      their quality. In this sense, NIRS has been used in combination with chemometric
      methods to predict the geographic origin of wheat grain and flour samples
      produced in different regions of Chile. Here, the spectral data obtained with
      NIRS were analysed using a supervised pattern recognition method, Discriminat
      Partial Least Squares (DPLS). The method correctly classified 76% of the wheat
      grain samples and between 90% and 96% of the flour samples according to their
      geographic origin. The results show that NIRS, together with chemometric methods,
      provides a rapid tool for the classification of wheat grain and flour samples
      according to their geographic origin. 

PMID- 24128549
TI  - Determination of polycyclic aromatic hydrocarbons in smoked and non-smoked black
      teas and tea infusions.
AB  - This study describes the occurrence of polycyclic aromatic hydrocarbons (PAHs) in
      smoked tea and tea infusions, via the monitoring of benzo(a)anthracene, chrysene,
      benzo(b)fluoranthene and benzo(a)pyrene (PAH4) that have been chosen as
      indicators for the occurrence of PAHs in food by the European Food Safety Agency.
      The concentrations ranged from 1.2 MUg/kg for benzo(b)fluoranthene to 125.0
      MUg/kg for benzo(a)anthracene in smoked tea leaves, and from 0.6 MUg/L for
      benzo(a)anthracene to 1.2 MUg/L for benzo(b)fluoranthene in smoked tea infusions.
      Benzo(a)pyrene was never detected in infusions. The concentrations in non-smoked
      tea leaves ranged from 0.6 MUg/kg for benzo(a)anthracene to 10.8 MUg/kg for
      benzo(b)fluoranthene. It was shown that the concentrations of benzo(a)anthracene
      and chrysene were higher in smoked tea than in non-smoked tea while no difference
      was observed for benzo(b)fluoranthene and benzo(a)pyrene. The concentrations of
      PAHs in tea infusions are low compared to other foodstuffs, but the migration
      rates from leaves into water are high (82-123%).

PMID- 24128550
TI  - Detection of thiabendazole applied on citrus fruits and bananas using surface
      enhanced Raman scattering.
AB  - Thiabendazole (TBZ) is a chemical fungicide and parasiticide largely used in food
      industry against mold and blight in vegetables and fruits during transportation
      and long term deposit. We investigated the possibility to detect and monitor the
      TBZ from the chemically treated bananas and citrus fruits available on Romanian
      market, using surface enhanced Raman spectroscopy (SERS) with a compact,
      portable, mini-Raman spectrometer. To assess the potential of the technique for
      fast, cheap and sensitive detection, we report the first complete vibrational
      characterization of the TBZ in a large pH and concentration range in conjunction
      with the density functional theory (DFT) calculations. From the relative
      intensity of the specific SERS bands as a function of concentration, we estimated
      a total amount of TZB as 78 mg/kg in citrus fruits, 13 times higher than the
      maximum allowed by current regulations, whereas in banana fruit the value was in
      the allowed limit.

PMID- 24128551
TI  - A laboratory efficient method for intramuscular fat analysis.
AB  - A new procedure to extract intramuscular fat (IMF) was developed to minimize
      sample amount, solvent use and time of analysis. Lyophilised samples (200mg) were
      accurately weighed in a safe-lock micro test tube, homogenized in 1.5 mL
      dichloromethane-methanol (8:2) and mixed in a mixer mill (MM400, Retsch
      technology). The final biphasic system was separated by centrifugation (8 min,
      10,000 rpm). The extraction was repeated three times. Solvent was evaporated
      under nitrogen stream and lipid content was gravimetrically determined. Results
      from 64 determinations were compared to those obtained with other referred method
      and showed a linear response over the whole range of IMF content (1.6-6.9 g/100 g
      sample). Moreover, the analysis with different methodology of six replica from
      the same sample showed lowest variability (standard deviation intra-method) for
      the new methodology proposed over a wide range of IMF content. A cost and time
      efficient lipid extraction procedure was developed without loss of precision and
      accuracy and with a fatty acid profile comparable to other protocols.

PMID- 24128552
TI  - A thermostable exo-beta-fructosidase immobilised through rational design.
AB  - Thermotoga maritima exo-beta-fructosidase (BfrA) secreted by a recombinant Pichia
      pastoris strain was optimally immobilised on Glyoxyl-Sepharose CL 4B using the
      Rational Design of Immobilised Derivatives (RDID) strategy. Covalent attachment
      of the N-glycosylated BfrA onto the activated support at pH 10 allowed total
      recovery of the loaded enzyme and its activity. The immobilisation process caused
      no variation in the catalytic properties of the enzyme and allowed further
      enhancement of the thermal stability. Complete inversion of cane sugar (2.04 M)
      in a batch stirred tank reactor at 60  degrees C was achieved with a productivity
      of 22.2 g of substrate hydrolysed/gram of biocatalyst/hour. Half-life of the
      immobilised enzyme of 5 days at 60  degrees C was determined in a continuously
      operated fixed-bed column reactor. Our results promote the applicability of the
      BfrA-immobilised biocatalyst for the complete hydrolysis of concentrated sucrose
      solutions under industrial conditions, especially at a high reaction temperature.

PMID- 24128553
TI  - Cholesterol oxidation and astaxanthin degradation in shrimp during sun drying and
      storage.
AB  - Dried salted shrimps are made from raw shrimps, which are cooked and dried under
      direct sunlight. The preparation and storage include treatments and conditions
      that can promote oxidative changes in different components. The aim of this study
      was to monitor the formation of major cholesterol oxidation products and the
      changes in the astaxanthin content and fatty acid profile in dried salted shrimp
      during cooking, sun drying and storage. During sun drying, most of the
      astaxanthin (75%) was degraded in cooked shrimp, while cholesterol oxidation
      products (COPs) showed a dramatic increase (8.6-fold), reaching a total
      concentration of 372.9 +/- 16.3 MUg/g of lipids. Further storage favoured both
      astaxanthin degradation (83%) and COPs formation (886.6 +/- 97.9 MUg/g of lipids
      after 90 days of storage). The high degradation of astaxanthin and the elevated
      formation of COPs during sun drying and storage indicate the necessity to re
      evaluate the processing and storage conditions of salted dried shrimp.

PMID- 24128554
TI  - Proteolytic characterisation in grass carp sausage inoculated with Lactobacillus
      plantarum and Pediococcus pentosaceus.
AB  - The proteolysis in grass carp sausages inoculated with Lactobacillus plantarum
      ZY40 and Pediococcus pentosaceus GY23 was investigated. As fermentation
      progressed, sarcoplasmic and myofibrillar proteins in both sausages were
      obviously degraded, and the proteolytic process was more intense in sausages
      inoculated with P. pentosaceus GY23. The increases in alpha-amino nitrogen,
      trichloroacetic acid (TCA)-soluble peptides and free amino acids were also
      detected in both sausages. The differences in alpha-amino nitrogen content and
      free amino acids concentration were due to the activity of inoculated lactic acid
      bacteria, while endogenous enzymes contributed to the release of TCA-soluble
      peptides. Our findings indicate that lactic acid bacteria influence proteolytic
      characterisation in fermented fish sausage, with strain-dependent activity. 

PMID- 24128555
TI  - Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP
      IV) hydrolysis.
AB  - In silico digestion of milk protein-derived peptides with gastrointestinal enzyme
      activities was used to predict the release of peptides with a Pro residue at
      position 2 from the N terminus. These peptides are known to act as preferred
      dipeptidyl peptidase IV (DPP-IV) substrates. Five casein-derived synthetic
      peptides (Ile-Pro-Ile-Gln-Tyr, Leu-Pro-Leu-Pro-Leu, Tyr-Pro-Tyr-Tyr, Leu-Pro-Tyr
      Pro-Tyr and Ile-Pro-Ile) and a casein (CasH), whey (WPH) and lactoferrin
      hydrolysate (LFH) generated with gastrointestinal enzymes were incubated with DPP
      IV at 37  degrees C for 18 or 24h. Peptide breakdown was evident following
      incubation with DPP-IV. Different modes of DPP-IV inhibition were observed
      depending on the test compound. Ile-Pro-Ile-Gln-Tyr, Tyr-Pro-Tyr-Tyr and Leu-Pro
      Tyr-Pro-Tyr were substrate-, Leu-Pro-Leu-Pro-Leu and CasH were prodrug- while WPH
      and LFH were true DPP-IV inhibitors. These results are relevant for the
      bioactivity and bioavailability of functional foods targeting DPP-IV inhibition
      with potential blood glucose regulatory properties in humans.

PMID- 24128556
TI  - Rapid and effective sample clean-up based on magnetic multiwalled carbon
      nanotubes for the determination of pesticide residues in tea by gas
      chromatography-mass spectrometry.
AB  - In this work, amine-functionalised magnetic nanoparticles and multiwalled carbon
      nanotubes (MNPs/MWCNTs) composites were synthesised by a simple method and
      applied as an adsorbent for rapid clean-up of acetonitrile extracts of tea
      samples prior to analysing eight pesticide residues by gas chromatography-mass
      spectrometry. Several parameters affecting the sampling and treatment efficiency
      were investigated, including extraction solvent, sonication time, weight ratio of
      MWCNTs to MNPs in the composites, amount of adsorbent, clean-up time and washing
      solution. Under the optimised conditions, the recoveries obtained for each
      pesticide ranged from 72.5% to 109.1% with relative standard deviations lower
      than 12.6%. Limit of quantification ranged from 0.02 to 0.08 mg kg-1. The
      established method was successfully applied to the analysis of pesticide residues
      in real tea samples. The results indicated that the use of MNPs/MWCNTs composites
      allowed the simple and expeditious clean-up of complex tea samples for subsequent
      determination of pesticide residues.

PMID- 24128557
TI  - Cereal foods are the major source of betaine in the Western diet--analysis of
      betaine and free choline in cereal foods and updated assessments of betaine
      intake.
AB  - Betaine and its precursor choline are important components of one-carbon
      metabolism, remethylating homocysteine into methionine and providing methyl
      groups for DNA methylation. Cereals are the main source of betaine in the diet,
      though there is little literature available on the content of betaine in cereal
      products, nor on betaine intake from cereals. Betaine and free-choline
      concentrations were measured by liquid-chromatography with tandem mass
      spectrometry in a wide range of commercially available cereal foods and cereal
      fractions. Whole grain wheat and related fractions were the best overall common
      source of betaine, while the pseudocereal quinoa had the highest amount of
      betaine measured (3900 MUg/g). Based on estimates of dietary intake data cereal
      foods provide approximately 60-67% of betaine in Western diets, and 20-40% of
      betaine in South-East Asian diets. Average intake of betaine was 131 mg/d, well
      below those used in intervention studies using betaine to lower blood
      homocysteine.

PMID- 24128558
TI  - Comparison of scavenging capacities of vegetables by ORAC and EPR.
AB  - Reactive oxygen species (ROS) are considered to be causative agents of many
      health problems. In spite of this, the radical-specific scavenging capacities of
      food samples have not been well studied. In the present work, we have developed
      an electron paramagnetic resonance (EPR) spin trapping method for analysis of the
      scavenging capacities of food samples for multiple ROS, utilising the same
      photolysis procedure for generating each type of radical. The optimal conditions
      for effective evaluation of hydroxyl, superoxide, and alkoxyl radical scavenging
      capacity were determined. Quantification of radical adducts was found to be
      highly reproducible, with variations of less than 4%. The optimised EPR spin
      trapping method was used to analyse the scavenging capacities of 54 different
      vegetable extracts for multiple radicals, and the results were compared with
      oxygen radical absorption capacity values. Good correlations between the two
      methods were observed for superoxide and alkoxyl radicals, but not for hydroxyl. 

PMID- 24128559
TI  - Phenolic profiling of the skin, pulp and seeds of Albarino grapes using hybrid
      quadrupole time-of-flight and triple-quadrupole mass spectrometry.
AB  - This paper describes for the first time a complete characterisation of the
      phenolic compounds in different anatomical parts of the Albarino grape. The
      application of high-performance liquid chromatography coupled with two
      complementary techniques, hybrid quadrupole time-of-flight and triple-quadrupole
      mass spectrometry, allowed the phenolic composition of the Albarino grape to be
      unambiguously identified and quantified. A more complete phenolic profile was
      obtained by product ion and precursor ion scans, while a neutral loss scan at 152
      u enabled a fast screening of procyanidin dimers, trimers and their galloylated
      derivatives. The compounds were confirmed by accurate mass measurements in QqToF
      MS and QqToF-MS/MS modes at high resolution, and good fits were obtained for all
      investigated ions, with errors ranging from 0.2 to 4.5 mDa. To the best of our
      knowledge, two flavanol monomer hexosides were detected in the grape berry for
      the first time. 

PMID- 24128560
TI  - Peanut skins-fortified peanut butters: effect of processing on the phenolics
      content, fibre content and antioxidant activity.
AB  - Incorporation of ground peanut skins (PS) into peanut butter at 1.25%, 2.5%,
      3.75%, and 5.0% (w/w) resulted in a marked concentration-dependent increase in
      both the total phenolics content (TPC) and antioxidant activity. Using dry
      blanched PS to illustrate, the TPC increased by 86%, 357%, 533%, and 714%,
      respectively, compared to the peanut butter control devoid of PS; the total
      proanthocyanidins content (TPACs) rose by 633%, 1933%, 3500%, and 5033%,
      respectively. NP-HPLC detection confirmed that the increase in the phenolics
      content was attributed to the endogenous proanthocyanidins of the PS, which were
      characterised as dimers to nonamers by NP-HPLC/ESI-MS. FRAP values increased
      correspondingly by 62%, 387%, 747%, and 829%, while H-ORAC(FL) values grew by
      53%, 247%, 382%, and 415%, respectively. The dietary fibre content of dry
      blanched PS was ~55%, with 89-93% being insoluble fibre. Data revealed that PS
      addition enhances the antioxidant capacity of the peanut butter, permits a "good
      source of fibre" claim, and offers diversification in the market's product line.

PMID- 24128561
TI  - Characterisation of Maillard reaction products derived from LEKFD--a pentapeptide
      found in beta-lactoglobulin sequence, glycated with glucose--by tandem mass
      spectrometry, molecular orbital calculations and gel filtration chromatography
      coupled with continuous photodiode array.
AB  - Maillard reaction peptides (MRPs) contribute to taste, aroma, colour, texture and
      biological activity. However, peptide degradation or the cross-linking of MRPs in
      the Maillard reaction has not been investigated clearly. A peptide of LEKFD, a
      part of beta-lactoglobulin, was heated at 110  degrees C for 24h with glucose and
      the reaction products were analysed by HPLC with ODS, ESI-MS, ESI-MS/MS and HPLC
      with gel-filtration column and DAD detector. In the HPLC fractions, an imminium
      ion of LEK*FD, a pyrylium ion or a hydroxymethyl furylium ion of LEK*FD, and KFD
      and EK were detected by ESI-MS. Therefore, those products may be produced by the
      Maillard reaction. The molecular orbital of glycated LEKFD at the lysine epsilon
      amino residue with Schiff base form was calculated by MOPAC. HPLC with gel
      filtration column showed cross-linking and degradation of peptides.

PMID- 24128562
TI  - Effect of farming systems on the yield, quality parameters and sensory properties
      of conventionally and organically grown potato (Solanum tuberosum L.) tubers.
AB  - The objectives of this two-year research were to study the impact of two
      different farming types, conventional and organic, on the yield and sensory
      properties of five Lithuanian varieties of potato tuber. The parameters and
      properties examined were: phenolic acids; dry matter and starch content; and the
      spread and intensity of Phytophthora infestans growth. It was determined that
      potato yield fluctuates with the variety, but for conventional farming it is
      significantly (p<0.05) higher than that obtained by organic farming. The farming
      type has no significant effect (p>0.05) on the content of phenolic acids. No
      significant effect (p>0.05) of farming type on dry matter and starch content, or
      sensory properties was found. No significant relation (p>0.05) was found between
      the content of phenolic acids and P. infestans spread. The spread of P. infestans
      was faster and infection was heavier in organically grown potatoes. 

PMID- 24128563
TI  - Enrichment of wheat chips with omega-3 fatty acid by flaxseed addition: textural
      and some physicochemical properties.
AB  - In the present study, wheat chips enriched with flaxseed flour were produced and
      response surface methodology was used for the studying the simultaneous effects
      of flaxseed level (10-20%), frying temperature (160-180  degrees C) and frying
      time (40-60 s) on some physicochemical, textural and sensorial properties and
      fatty acid composition of wheat chips. Ridge analysis was conducted to determine
      the optimum levels of processing variables. Predictive regression equations with
      adequate coefficients of determination (R2 >= 0.705) to explain the effect of
      processing variables were constructed. Addition of flaxseed flour increased the
      dry matter and protein content of samples and increase of frying temperature
      decreased the hardness values of wheat chips samples. Increment in flaxseed level
      provided an increase in unsaturated fatty acid content namely omega-3 fatty acids
      of wheat chips samples. Overall acceptability of chips increased with the
      increase of frying temperature. Ridge analysis showed that maximum taste score
      would be at flaxseed level = 10%, frying temperature = 180  degrees C and frying
      time = 50 s.

PMID- 24128564
TI  - Sample preparation: a critical step in the analysis of cholesterol oxidation
      products.
AB  - In recent years, cholesterol oxidation products (COPs) have drawn scientific
      interest, particularly due to their implications on human health. A big number of
      these compounds have been demonstrated to be cytotoxic, mutagenic, and
      carcinogenic. The main source of COPs is through diet, and particularly from the
      consumption of cholesterol-rich foods. This raises questions about the safety of
      consumers, and it suggests the necessity for the development of a sensitive and a
      reliable analytical method in order to identify and quantify these components in
      food samples. Sample preparation is a necessary step in the analysis of COPs in
      order to eliminate interferences and increase sensitivity. Numerous publications
      have, over the years, reported the use of different methods for the extraction
      and purification of COPs. However, no method has, so far, been established as a
      routine method for the analysis of COPs in foods. Therefore, it was considered
      important to overview different sample preparation procedures and evaluate the
      different preparative parameters, such as time of saponification, the type of
      organic solvents for fat extraction, the stationary phase in solid phase
      extraction, etc., according to recovery, precision and simplicity. 

PMID- 24128565
TI  - Feasibility of microwave-induced combustion for trace element determination in
      Engraulis anchoita by ICP-MS.
AB  - A method based on microwave-induced combustion (MIC) was developed for fish
      (Engraulis anchoita) digestion and subsequent determination of As, Cd, Co, Cr,
      Cu, Fe, Mn, Mo, Ni, Se, and Zn by inductively coupled plasma mass spectrometry
      (ICP-MS). A reflux step (5 min) was applied to improve absorption and recovery of
      analytes. Nitric acid was investigated as absorbing solution and suitable results
      were achieved using 5 mol L-1 HNO3. Microwave-assisted digestion in closed
      vessels using concentrated HNO3 was also evaluated for comparison of results.
      Both sample preparation methods were considered suitable for sample digestion but
      MIC was preferable not only because diluted HNO3 can be used as absorbing
      solution but also because it provides higher efficiency of digestion and also
      better limits of detection. Accuracy was evaluated by the analysis of certified
      reference materials (DORM-2 and TORT-2) after MIC digestion with subsequent
      determination by ICP-MS. Agreement with certified values was better than 94%.

PMID- 24128566
TI  - Characterisation of lipid fraction of marine macroalgae by means of
      chromatography techniques coupled to mass spectrometry.
AB  - In this work the characterisation of the lipid fraction of several species of
      marine macro algae gathered along the eastern coast of Sicily is reported. Two
      species of green marine algae (Chloropyceae), two species of red marine algae
      (Rhodophyceae) and four species of brown marine algae (Pheophyceae) were
      evaluated in terms of fatty acids, triacylglycerols, pigments and phospholipids
      profile. Advanced analytical techniques were employed to fully characterise the
      lipid profile of these Mediterranean seaweeds, such as GC-MS coupled to a novel
      mass spectra database supported by the simultaneous use of linear retention index
      (LRI) for the identification of fatty acid profile; LC-MS was employed for the
      identification of triacylglycerols (TAGs), carotenoids and phospholipids; the
      determination of accurate mass was carried out on carotenoids and phospholipids.
      Quantitative data are reported on fatty acids and triacylglycerols as relative
      percentage of total fraction. 

PMID- 24128567
TI  - Floral classification of honey using liquid chromatography-diode array detection
      tandem mass spectrometry and chemometric analysis.
AB  - A high performance liquid chromatography-diode array detection-tandem mass
      spectrometry (HPLC-DAD-MS/MS) method for the floral origin traceability of chaste
      honey and rape honey samples was firstly presented in this study. Kaempferol,
      morin and ferulic acid were used as floral markers to distinguish chaste honey
      from rape honey. Chromatographic fingerprinting at 270 nm and 360 nm could be
      used to characterise chaste honey and rape honey according to the analytical
      profiles. Principal component analysis (PCA), partial least squares (PLS),
      partial least squares-discrimination analysis (PLS-DA) and soft independent
      modeling of class analogy (SIMCA) were applied to classify the honey samples
      according to their floral origins. The results showed that chaste honey and rape
      honey could be successfully classified by their floral sources with the
      analytical methods developed through this study and could be considered
      encouraging and promising for the honey traceability from unifloral or
      multifloral nectariferous sources.

PMID- 24128568
TI  - Molecular structural differences between low methoxy pectins induced by pectin
      methyl esterase II: effects on texture, release and perception of aroma in gels
      of similar modulus of elasticity.
AB  - Six low-methoxy pectins with different degrees of methylesterification and
      amidation, and molecular weights were used to prepare gels with similar moduli of
      elasticity by varying the concentrations of pectin and calcium phosphate. Five
      aroma compounds were added to the gels and their sensory textural properties,
      release and perception of aromas were investigated. Sensory firmness,
      springiness, adhesiveness, chewiness and cohesiveness differed according to the
      gel type, even though the moduli of elasticity were not significantly different
      (p<0.05). Release and perception of aromas also displayed significant difference
      according to the gel type (p<0.05). Low-methoxy amidated pectin exhibited the
      lowest release and perception for all the aroma compounds, while pectin
      methylesterase-treated pectin gels exhibited relatively higher aroma release and
      perception. These results showed that the structural properties of pectins and
      gelling factors that increase the non-polar character of the gel matrices could
      decrease the release and perception of aromas in pectin gel systems. 

PMID- 24128569
TI  - Simultaneous determination of 14 oil-soluble synthetic dyes in chilli products by
      high performance liquid chromatography with a gel permeation chromatography clean
      up procedure.
AB  - A method was developed for the simultaneous determination of 14 fat-soluble dyes
      in chilli products. The samples were extracted with hexane/acetone. The cleanup
      was performed with gel permeation chromatography (GPC) cleanup system. A HPLC
      separation was performed using variable wavelength detector and a gradient
      elution with 0.1% formic acid and methanol-acetonitrile (1:1, v/v) as the mobile
      phases. Good linearity (R2 >= 0.995) was observed between 0.1 and 5.0 MUg/mL.
      Detection limits of the investigated dyes, which were evaluated at signal to
      noise ratio of 3, were in the ranges of 11-71 MUg/kg. The recoveries of the 14
      synthetic colourants in three matrices ranged from 73.4% to 103.5%. Relative
      standard deviations ranged from 3.7% to 12.3%. The method has been successfully
      used for the determination of banned dyes in real samples.

PMID- 24128570
TI  - Content changes of bitter compounds in 'Guoqing No.1' Satsuma mandarin (Citrus
      unshiu Marc.) during fruit development of consecutive 3 seasons.
AB  - The main bitter compounds (nomilin, limonin and naringin) in the fruit tissues of
      'Guoqing No.1' Satsuma mandarin (Citrus unshiu Marc.) were determined throughout
      the fruit development of 3 consecutive growing seasons. Although fluctuating
      largely at the corresponding developing stages of the 3 years, the contents of
      these compounds in fruit tissues mostly displayed a declining trend, which
      implied that the rhythm of the metabolism of these bitter compounds was not
      consistent among years and was largely growing season dependent. Regarding their
      distribution, fruit flavedo might be a weak sink that contained the lowest level
      of naringin, while the segment membrane accumulated large amount of limonin and
      nomilin, which indicated a possible tissue bias pattern for biosynthesis or
      accumulation of those compounds. Partial correlation coefficient analysis
      revealed a synergistic accumulation of naringin and the two limonoid aglycones in
      fruit tissues during fruit development, indicating an integrated metabolism of
      flavonoids and limonoids.

PMID- 24128571
TI  - Vitiquinolone--a quinolone alkaloid from Hibiscus vitifolius Linn.
AB  - Phytochemical investigations of the powdered root of Hibiscus vitifolius Linn.
      (Malvaceae) was extracted successively with n-hexane and chloroform. Analysis of
      the n-hexane extract by GC-MS led to the identification of twenty-six components
      by comparison of their mass spectra with GC-MS library data. A novel quinolone
      alkaloid, vitiquinolone (5) together with eight known compounds viz. beta-Amyrin
      acetate (1), n-octacosanol (2), beta-Amyrin (3), stigmasterol (4), xanthyletin
      (6), alloxanthoxyletin (7), xanthoxyletin (8) and betulinic acid (9) were
      isolated from chloroform extract by column chromatography over silica gel. The
      structure of vitiquinolone was established on the basis of spectroscopic methods
      including UV, IR, 1D, 2D NMR and ESI-MS. The known compounds were identified on
      the basis of their physical and spectroscopic data as reported in the literature.

PMID- 24128572
TI  - Analysis of the monosaccharide composition of water-soluble polysaccharides from
      Sargassum fusiforme by high performance liquid chromatography/electrospray
      ionisation mass spectrometry.
AB  - Sargassum fusiforme (hijiki) is the well-known edible algae, whose
      polysaccharides have been proved to possess interesting bioactivities like
      antitumor, antioxidant, antimicrobial and immunomodulatory activities. A facile
      and sensitive method based on high-performance liquid chromatography method of
      pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP) coupled with
      electrospray ionisation mass spectrometry (HPLC/ESI-MS) has been established for
      the analysis of the monosaccharide composition of polysaccharides in S.
      fusiforme. Monosaccharides have been converted into PMP-labelled derivatives with
      aqueous ammonia as a catalyst at 70  degrees C for 30 min. The optimisation of
      the pre-column derivatization process was studied. The LODs of the
      monosaccharides were in the range from 0.01 to 0.02 nmol. PMP-labelled mixture of
      monosaccharides has been well separated by a reverse-phase HPLC and detected by
      on-line ESI-MS method under optimised conditions. The mobile phase of elution
      system was chosen as acetonitrile (solvent A) and 20mM aqueous ammonium acetate
      (solvent B) (pH 3.0) with Zorbax XDB-C18 column at 30  degrees C for the
      separation of the monosaccharide derivatives. Identification of the
      monosaccharides composition was carried out by analysis with mass spectral
      behaviour and chromatography characteristics of 1-phenyl-3-methyl-5-pyrazolone
      (PMP) labelled monosaccharides. All PMP-labelled derivatives display high
      chemical stabilities, whose regular MS fragmentation is specific for reducing
      labelled sugars. The result showed that the S. fusiforme polysaccharide consisted
      of mannose, glucose, galactose, xylose, fucose and glucuronic acid or
      galacturonic acid, or both uronic acids.

PMID- 24128573
TI  - Effects of granulation on organic acid metabolism and its relation to mineral
      elements in Citrus grandis juice sacs.
AB  - We investigated the effects of granulation on organic acid metabolism and its
      relation to mineral elements in 'Guanximiyou' pummelo (Citrus grandis) juice
      sacs. Granulated juice sacs had decreased concentrations of citrate and
      isocitrate, thus lowering juice sac acidity. By contrast, malate concentration
      was higher in granulated juice sacs than in normal ones. The reduction in citrate
      concentration might be caused by increased degradation, as indicated by enhanced
      aconitase activity, whilst the increase in malate concentration might be caused
      by increased biosynthesis, as indicated by enhanced phosphoenolpyruvate
      carboxylase (PEPC). Real time quantitative reverse transcription PCR (qRT-PCR)
      analysis showed that the activities of most acid-metabolizing enzymes were
      regulated at the transcriptional level, whilst post-translational modifications
      might influence the PEPC activity. Granulation led to increased accumulation of
      mineral elements (especially phosphorus, magnesium, sulphur, zinc and copper) in
      juice sacs, which might be involved in the incidence of granulation in pummelo
      fruits. 

PMID- 24128574
TI  - Novel antioxidative peptides from the protein hydrolysate of oysters (Crassostrea
      talienwhanensis).
AB  - The antioxidative activity of hydrolysate peptides from oysters (Crassostrea
      talienwhanensis) was investigated. After hydrolysis with subtilisin, the yields
      of the peptides that were soluble in trichloroacetic acid (TCA-soluble) and the
      antioxidant activities of the resulting hydrolysate were determined using an
      orthogonal design and a hydroxyl radical scavenging reaction. The hydrolysate was
      fractionated using Sephadex G-15 gel filtration chromatography, and the two
      resulting bioactive peptides were subsequently purified by RP-HPLC with a
      Kromasil C18 (ODS) column. The amino acid sequences were analyzed by nano-ESI
      MS/MS. The critical reaction temperature, pH, hydrolysis time and enzyme-to
      substrate (E/S) ratio were determined for the optimum hydrolysis with subtilisin,
      and the E/S ratio was found to be the most critical reaction condition. The amino
      acid sequences of the peptides (518 and 440 Da) were proline-valine-methionine
      glycine-aspartic acid (PVMGA) and glutamine-histidine-glycine-valine (QHGV),
      respectively. These two novel peptides exhibited high antioxidative actions based
      on their hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      activities.

PMID- 24128575
TI  - Changes of phospholipase A2 and C activities during dry-cured duck processing and
      their relationship with intramuscular phospholipid degradation.
AB  - Phospholipid hydrolysis, as the main stage and cause of phopholipid degradation,
      is generally attributed to phospholipases. In this study, the changes of
      phospholipase A2 (PLA2) and C (PLC) activities, neutral lipid, free fatty acids
      and phospholipids in dry-cured duck leg muscles during processing, were examined.
      The composition of free fatty acids and neutral lipids increased significantly
      (P<0.05) with extension of processing time while the phospholipids composition
      decreased. The PLA2 and PLC activity decreased in the final product, but retained
      83.70% and 86.78% of their initial activities, respectively. The relative
      activities of both PLA2 and PLC highly correlated with the decline of
      phospholipids and the increase of free fatty acids. High correlations were also
      obtained between the relative activities of PLC and the increase of neutral lipid
      (P<0.01). All these results suggest that PLA2 and PLC contribute to the
      degradation of intramuscular phospholipids during the processing of dry-cured
      duck.

PMID- 24128576
TI  - Combined determination and confirmation of ethylenethiourea and propylenethiourea
      residues in fruits at low levels of detection.
AB  - In this work, a new method for the determination of ethylenethiourea (ETU) and
      propylenethiourea (PTU) in fruits and vegetables is presented. Different
      extraction and purification techniques, including matrix solid phase dispersion
      (MSPD) and solid-liquid extraction (SLE), followed by a clean-up step by solid
      phase extraction (SPE), were compared. The determination of ETU and PTU was
      performed by high performance liquid chromatography with diode array detection
      (HPLC/DAD) or by gas chromatography with mass spectrometry detection (GC/MS). The
      effect of several parameters on the extraction, separation and detection was
      studied. The proposed method based on solid-liquid extraction with acetonitrile,
      clean-up with Envicarb II/PSA cartridges and subsequent analysis by HPLC/DAD was
      characterised and applied to the analysis of fruits and vegetables from different
      countries. Analytes recoveries were between 71% and 94% with relative standard
      deviations (RSDs) ranging from 8% to 9.5%. Quantification limits obtained for ETU
      and PTU with the HPLC/DAD method were 7 and 16 MUg kg-1 in strawberries (fresh
      weight), respectively. For apples, they were 11 and 25 MUg kg-1, respectively.

PMID- 24128577
TI  - Geographical differentiation of dried lentil seed (Lens culinaris) samples using
      diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and
      discriminant analysis.
AB  - Diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and
      discriminant analysis were used for the geographical differentiation of dried
      lentil seed (Lens culinaris) samples. Specifically, 18 Greek samples and nine
      samples imported from other countries were distinguished using the 2250-1720 and
      1275-955 cm-1 spectral regions. The differentiation is complete. The combination
      of DRIFTS and discriminant analysis enables simple, rapid, cheap and accurate
      differentiation of commercial lentil seeds in terms of geographical origin.

PMID- 24128578
TI  - nrDNA ITS sequence based SCAR marker to authenticate Aconitum heterophyllum and
      Cyperus rotundus in Ayurvedic raw drug source and prepared herbal products.
AB  - To authenticate Ayurvedic medicinal plants Ativisha (Aconitum heterophyllum) and
      Musta (Cyperus rotundus) at the raw drug source and in prepared herbal products,
      nrDNA ITS sequence based SCAR markers were designed and validated spp.-specific
      SCAR primers gave amplicon of 415 bp and 134 bp, respectively, in authentic
      species. The SCAR primers (Cyr-FP and Cyr-RP) could identify tissue sample
      containing 750 MUg to 4.76 mg/100mg of Musta in complex mixtures of DNA extracted
      from commercial herbal drugs. Ativisha could not be identified through SCAR
      markers suggesting that authentic species may not been used to prepare herbal
      drugs despite its being labelled as one of the ingredients in formulations.
      Analysis of individual tubers of Ativisha and Musta assures the presence of
      admixtures in raw drug trade of Ativisha, indicates the need to monitor the basic
      raw material supply and concludes, supplying plant materials through cultivation
      to manufacturing industries can minimize the risks of adulteration.

PMID- 24128579
TI  - Sensory description of sweet wines obtained by the winemaking procedures of
      raisining, botrytisation and fortification.
AB  - The effect of winemaking procedures on the sensory modification of sweet wines
      was investigated. Garnacha Tintorera-based sweet wines were obtained by two
      different processes: by using raisins for vinification to obtain a naturally
      sweet wine and by using freshly harvested grapes with the stoppage of the
      fermentation by the addition of alcohol. Eight international sweet wines were
      also subjected to sensory analysis for comparative description purposes. Wines
      were described with a sensory profile by 12 trained panellists on 70 sensory
      attributes by employing the frequency of citation method. Analysis of variance of
      the descriptive data confirmed the existence of subtle sensory differences among
      Garnacha Tintorera-based sweet wines depending on the procedure used for their
      production. Cluster analysis emphasised discriminated attributes between the
      Garnacha Tintorera-based and the commercial groups of sweet wines for both those
      obtained by raisining and by fortification. Several kinds of discriminant
      functions were used to separate groups of sweet wines--obtained by botrytisation,
      raisining and fortification--to show the key descriptors that contribute to their
      separation and define the sensory perception of each type of wine.

PMID- 24128580
TI  - Variability of antioxidant and antibacterial effects of essential oils and
      acetonic extracts of two edible halophytes: Crithmum maritimum L. and Inula
      crithmoides L.
AB  - This work aimed to assess the richness of the food halophytes Crithmum maritimum
      and Inula crithmoides on phenolics and essential oils (EOs) and to evaluate the
      antioxidant and antibacterial potential of these metabolites. Results displayed
      that extract of I. crithmoides possesses considerable contents of phenolic
      compounds (14.1mg GAE.g-1 DW) related to important antioxidant activities (IC50 =
      13 MUg ml-1 for the DPPH test) as compared to C. maritimum. C. maritimum EOs
      composition is dominated by oxygenated monoterpenes, while I. crithmoides one is
      mainly consisted by monoterpene hydrocarbons. EOs have low antioxidant activity
      as compared to acetone extracts; nevertheless, they show best antimicrobial
      activity. A significant variability is also depicted between the provenances of
      each species and depended on the chemical nature of antioxidant and antibacterial
      molecules as well as the used tests.

PMID- 24128581
TI  - Validation of a new in vitro dynamic system to simulate infant digestion.
AB  - Understanding the mechanisms of infant formula disintegration in the infant
      gastrointestinal tract is a key step for developing new formulas with health
      benefits for the neonate. For ethical reasons, the access to in vivo data
      obtained on infants is limited. The use of animal models can be an alternative
      but these experiments are labour intensive, expensive and results obtained show
      high inter-individual variability, making their interpretation difficult. The aim
      of this work was to develop a simple in vitro dynamic gastrointestinal digestion
      system, for studying infant formula digestion, and to validate it by comparing
      the kinetics of proteolysis obtained in vitro with in vivo data collected from
      piglets. Results showed a good correlation between in vitro and in vivo data and
      confirmed the rapid hydrolysis of caseins in gastric conditions, whereas whey
      proteins appeared more resistant to digestion. 

PMID- 24128582
TI  - Laccase-catalysed oxidation of ferulic acid and ethyl ferulate in aqueous medium:
      a green procedure for the synthesis of new compounds.
AB  - The enzymatic oxidation of ferulic acid (FA) and ethyl ferulate (EF) with
      Myceliophthora thermophila laccase, as biocatalyst, was performed in aqueous
      medium using an eco-friendly procedure to synthesize new active molecules. First,
      the commercial laccase was ultrafiltrated allowing for the elimination of
      phenolic contaminants and increasing the specific activity by a factor of 2.
      Then, kinetic parameters of this laccase were determined for both substrates (FA,
      EF), indicating a higher substrate affinity for ethyl ferulate. Additionally,
      enzymatic oxidation led to the synthesis of a FA-major product, exhibiting a
      molecular mass of 386 g/mol and a EF-major product with a molecular mass of 442
      g/mol. Structural analyses by mass spectrometry allowed the identification of
      dimeric derivatives. The optical properties of the oxidation products showed the
      increase of red and yellow colours, with FA-products compared to EF-products.
      Additionally, enzymatic oxidation led to a decrease of antioxidant and cytotoxic
      activities compared to initial substrates. Consequently, this enzymatic procedure
      in aqueous medium could provide new compounds presenting optical, antioxidant and
      cytotoxic interest.

PMID- 24128583
TI  - Biophysical evaluation of physiological effects of gilthead sea bream (Sparus
      aurata) farming using FTIR spectroscopy.
AB  - Sparus aurata is one of the two most important cultured fish species in the
      Mediterranean region. The present work investigates the effects of culturing in
      S. aurata liver tissue at the molecular level using Fourier Transform Infrared
      (FTIR) spectroscopy. FTIR spectroscopy revealed dramatic differences between the
      wild and aquacultured fish liver cells, which mainly indicated that the level of
      glycogen increased in the aquacultured samples and the protein/lipid ratio
      decreased by 42.29% indicating that triglycerides and cholesterol esters
      increased and the protein content decreased in the aquacultured samples. The
      15.99% increase in the level of unsaturation indicated elevated lipid
      peroxidation. Structural/organisational changes in the nucleic acids along with
      increased transcriptional status of the liver tissue cells were observed in the
      cultured fish tissue. All these results indicated that culturing induces
      significant changes in fish physiology. In addition FTIR spectroscopy is a
      promising method to monitor the physiological changes in fish physiology. 

PMID- 24128584
TI  - Screening of volatile compounds in honey using a new sampling strategy combining
      multiple extraction temperatures in a single assay by HS-SPME-GC-MS.
AB  - This paper proposes a new optimization strategy for the extraction of volatile
      compounds from honey samples using headspace solid-phase microextraction (HS
      SPME) and separation/detection by gas chromatography-mass spectrometry (GC-MS).
      The new optimization strategy was based on the use of three different extraction
      temperatures in a single assay, aiming at extracting a high number of compounds
      with wide range of volatilities. As an analytical tool, experimental designs were
      used for the optimization. The variables extraction time (10-80 min), extraction
      temperature (0-60  degrees C), water volume (0.5-5 mL) and percentage of sodium
      chloride saturation in water (0-100%) were optimised using a five-level
      fractional central composite design with CAR/DVB/PDMS fibre. The final optimised
      combination of extraction times at each temperature was 60 min with the sample
      temperature being held at 60  degrees C for 36 min, 40  degrees C for 18 min and
      0  degrees C for 6 min. The proposed method was compared to conventional methods
      which employ one or two extraction temperatures. It was found that the proposed
      method presented better results considering the response in terms of the
      arithmetic means of the peak areas. The use of multiple extraction temperatures
      for the HS-SPME procedure proved to be an excellent alternative for the screening
      of compounds present in honey with a wide range of volatilities.

PMID- 24128585
TI  - Comparison of cytotoxic extracts from fruiting bodies, infected insects and
      cultured mycelia of Cordyceps formosana.
AB  - A resazurin method was employed to test and compare cytotoxicity of extracts from
      fruiting bodies, insects and cultured mycelia of Cordyceps formosana against
      Chinese hamster ovary (CHO) cells. Results showed that the cultured mycelia had
      much stronger cytotoxicity than that of the fruiting bodies and infected insects.
      This suggests that using cultured mycelia to substitute a natural Cordyceps may
      result in poisoning. A combined method of HPLC-PAD-HRMS and cytotoxic analysis
      revealed that the most toxic compound (Compound 1) was found mainly in the
      cultured mycelia and also a small amount in the infected insect body of the
      Cordyceps, but not in the fruiting body. The second toxic compound (Compound 2)
      was found in all structures of Cordyceps and in cultured mycelia. Different
      contents of the toxic compounds resulted in the different cytotoxicity of the
      extracts. Compound 1 and Compound 2 were prepared with preparative HPLC as yellow
      and orange powders, respectively. Cytotoxic tests showed that the median lethal
      dose (LD50) against CHO cells of Compound 1 was 18.3 +/- 0.2 and 103.7 +/- 5.9
      MUg/mL for Compound 2. Compound 1 and Compound 2 were identified as rugulosin and
      skyrin by HRMS, UV and NMR data. The two compounds were never previously isolated
      from the genera Cordyceps and Hirsutella and their cytotoxicity against CHO cells
      was also reported for the first time.

PMID- 24128586
TI  - Detection of genetically modified soybean in crude soybean oil.
AB  - In order to detect presence and quantity of Roundup Ready (RR) soybean in crude
      oil extracted from soybean seed with a different percentage of GMO seed two
      extraction methods were used, CTAB and DNeasy Plant Mini Kit. The amplifications
      of lectin gene, used to check the presence of soybean DNA, were not achieved in
      all CTAB extracts of DNA, while commercial kit gave satisfactory results.
      Comparing actual and estimated GMO content between two extraction methods, root
      mean square deviation for kit is 0.208 and for CTAB is 2.127, clearly
      demonstrated superiority of kit over CTAB extraction. The results of
      quantification evidently showed that if the oil samples originate from soybean
      seed with varying percentage of RR, it is possible to monitor the GMO content at
      the first stage of processing crude oil. 

PMID- 24128587
TI  - Application of taste sensing system for characterisation of enzymatic
      hydrolysates from shrimp processing by-products.
AB  - The objective of this study was to investigate the potential of an instrumental
      taste-sensing system to distinguish between shrimp processing by-products
      hydrolysates produced using different proteases and hydrolysis conditions, and
      the possible association of taste sensor outputs with human gustatory assessment,
      salt content, and bioactivity. Principal component analysis of taste sensor
      output data categorised samples according to the proteases used for hydrolysis.
      High umami sensor outputs were characteristic of bromelain- and Flavourzyme
      produced hydrolysates, compared to low saltiness and high bitterness outputs of
      Alcalase-produced hydrolysates, and high saltiness and low umami outputs of
      Protamex-produced hydrolysates. Extensively hydrolysed samples showed higher
      sourness outputs. Saltiness sensor outputs were correlated with conductivity and
      sodium content, while umami sensor responses were related to gustatory sweetness,
      bitterness and umami, as well as angiotensin-I converting enzyme inhibitory
      activity. Further research should explore the dose dependence and sensitivity of
      each taste sensor to specific amino acids and peptides. 

PMID- 24128588
TI  - Detection of mandarin in orange juice by single-nucleotide polymorphism qPCR
      assay.
AB  - A dual-probe real time PCR (qPCR) DNA-based analysis was devised for the
      identification of mandarin in orange juice. A single nucleotide polymorphism at
      the trnL-trnF intergenic region of the chloroplast chromosome was confirmed in
      nine orange (Citrus sinensis) and thirteen commercial varieties of mandarin,
      including Citrus reticulata and Citrus unshiu species and a mandarin * tangelo
      hybrid. Two short minor-groove binding fluorescent probes targeting the
      polymorphic sequence were used in the dual-probe qPCR, which allowed the
      detection of both species in single-tube reactions. The similarity of PCR
      efficiencies allowed a simple estimation of the ratio mandarin/orange in the
      juice samples, which correlated to the measured difference of threshold cycle
      values for both probes. The limit of detection of the assay was 5% of mandarin in
      orange juice, both when the juice was freshly prepared (not from concentrate) or
      reconstituted from concentrate, which would allow the detection of fraudulently
      added mandarin juice. The possible use of the dual-probe system for quantitative
      measurements was also tested on fruit juice mixtures. qPCR data obtained from
      samples containing equal amounts of mandarin and orange juice revealed that the
      mandarin target copy number was approximately 2.6-fold higher than in orange
      juice. The use of a matrix-adapted control as calibrator to compensate the
      resulting C(T) bias allowed accurate quantitative measurements to be obtained.

PMID- 24128589
TI  - Dissipation kinetics of bifenazate in tea under tropical conditions.
AB  - Field experiments were conducted during April and May of 2011 in Valparai,
      Coonoor and Gudalur (Tamil Nadu, India) to determine the residues of bifenazate
      in black tea. From this study, residue levels of bifenazate at different harvest
      intervals, persistence, dissipation pattern during processing, rate constant and
      half-life values were calculated. Residues of bifenazate dissipated exponentially
      after spraying and at Gudalur trial, on the 16th day after application residues
      were below the maximum residue level of 0.02 mg/kg set by the European Union.
      However, no residues were detected in the tea brew. Regression lines drawn for
      bifenazate showed that it followed first order dissipation kinetics. Half-life
      values varied from 1.03 to 1.36 days for bifenazate and a pre-harvest interval of
      16 days is suggested.

PMID- 24128590
TI  - Structural elucidation of olive pomace fed sea bass (Dicentrarchus labrax) polar
      lipids with cardioprotective activities.
AB  - The purpose of this study was to structurally characterise the polar lipids of
      sea bass (Dicentrarchus labrax), fed with an experimental diet containing olive
      pomace (OP), that exhibit cardioprotective activities. OP has been added to
      conventional fish oil (FO) feed at 4% and this was the OP diet, having been
      supplemented as finishing diet to fish. Sea bass was aquacultured using either FO
      or OP diet. At the end of the dietary experiment, lipids in both samples of fish
      muscle were quantified and HPLC fractionated. The in vitro cardioprotective
      properties of the polar lipid fractions, using washed rabbit's platelets, have
      been assessed and the two most biologically active fractions were further
      analysed by mass spectrometry. The gas-chromatrograpy-mass spectrometric data
      shows that these two fractions contain low levels of myristic (14:0), oleic (18:1
      cis omega-9) and linoleic acids (18:2 omega-6), but high levels of palmitic
      (16:0) and stearic acids (18:0) as well as eicosadienoic acid (20:2 omega-6). The
      first fraction (MS1) also contained significant levels of arachidonic acid (20:4
      omega-6) and the omega-3 fatty acids: eicosapentaenoic acid (22:5) and
      docosahexaenoic acid (22:6). Electrospray-mass spectrometry elucidated that the
      lipid composition of the two fractions contained various diacyl
      glycerophospholipids species, where the majority of them have either 18:0 or 18:1
      fatty acids in the sn-1 position and either 22:6 or 20:2 fatty acids in the sn-2
      position for MS1 and MS2, respectively. Our research focuses on the
      structure/function relationship of fish muscle polar lipids and cardiovascular
      diseases and structural data are given for polar lipid HPLC fractions with strong
      cardioprotective properties. 

PMID- 24128591
TI  - A single injection of a sustained-release prostacyclin analog (ONO-1301MS)
      suppresses airway inflammation and remodeling in a chronic house dust mite
      induced asthma model.
AB  - ONO-1301, a novel prostacyclin agonist with thromboxane A2 synthase inhibitory
      activity, is a useful agent for ameliorating airway allergic inflammation;
      however, its short-action feature implies a requirement for the frequent
      administration of this drug. Therefore, we investigated the effects of ONO-1301
      loaded poly (d,l-lactic-co-glycolic acid) microspheres (ONO-1301MS; to release
      ONO-1301 for 3 weeks) on the airway inflammation and remodeling in chronic house
      dust mite (HDM)-induced model. Balb/c mice were exposed to an HDM extract
      intranasally for 5 days/week for 5 consecutive weeks. The mice received a single
      subcutaneous injection of ONO-1301MS or vehicle after 3 weeks of HDM exposure,
      followed by 2 additional weeks of HDM exposure. Forty-eight hours after the last
      HDM exposure, airway hyperresponsiveness to methacholine was assessed and
      bronchoalveolar lavage was performed. Lung specimens were excised and stained to
      check for goblet cell metaplasia, airway smooth muscle hypertrophy, and
      submucosal fibrosis. Mice receiving ONO-1301MS showed significantly lower airway
      hyperresponsiveness, airway eosinophilia, and induced T helper 2 cytokine
      production compared with mice receiving the vehicle. Histological findings such
      as goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal
      fibrosis were decreased in ONO-1301MS-treated mice compared with vehicle-treated
      mice. A single administration of ONO-1301MS achieved sustained elevation of its
      circulating level for 3 weeks. These data suggest that a single administration of
      ONO-1301MS may suppress airway hyperresponsiveness, airway allergic inflammation,
      and development of airway remodeling in chronic HDM-induced asthma model. This
      agent may be effective as an anti-inflammatory and remodeling drug in the
      practical treatment of asthma. 

PMID- 24128592
TI  - Use of an electronic patient-reported outcome measurement system to improve
      distress management in oncology.
AB  - OBJECTIVE: Management of patient distress is a critical task in cancer nursing
      and cancer practice. Here we describe two examples of how an electronic patient
      reported outcome (ePRO) measurement system implemented into routine oncology care
      can practically aid clinical and research tasks related to distress management.
      METHODS: Tablet personal computers were used to routinely complete a standardized
      ePRO review of systems surveys at point of care during every encounter in the
      Duke Oncology outpatient clinics. Two cases of use implementation are explored:
      (1) triaging distressed patients for optimal care, and (2) psychosocial program
      evaluation research. RESULTS: Between 2009 and 2011, the ePRO system was used to
      collect information during 17,338 Duke Oncology patient encounters. The system
      was used to monitor patients for psychosocial distress employing an electronic
      clinical decision support algorithm, with 1,952 (11.3%) referrals generated for
      supportive services. The system was utilized to examine the efficacy of a
      psychosocial care intervention documenting statistically significant improvements
      in distress, despair, fatigue, and quality of life (QOL) in 50 breast cancer
      patients. SIGNIFICANCE OF RESULTS: ePRO solutions can guide best practice
      management of cancer patient distress. Nurses play a key role in implementation
      and utilization.

PMID- 24128593
TI  - A Stroop Stepping Test (SST) using low-cost computer game technology
      discriminates between older fallers and non-fallers.
AB  - BACKGROUND: impaired stepping and reduced cognitive functioning have both been
      identified as fall-risk factors in older people. We developed a Stroop Stepping
      Test (SST) that combines stepping and response inhibition using low-cost computer
      game technology to provide a functional measure that reflects real-life behaviour
      and determined whether this test discriminates between older fallers and non
      fallers. METHODS: a cross-sectional study, including 103-independent living
      cognitively intact older people (70-93 years), was conducted. Participants were
      assessed on the SST and other outcome measures associated with fall-risk. The SST
      presented arrows on a computer screen with words written within them.
      Participants were asked to step in the direction indicated by the word and ignore
      the arrow orientation. Participants also reported whether they had fallen or not
      in the past 12 months. RESULTS: twenty-eight percent of participants reported
      falling in the past year. SST mean time per trial [OR: 1.72 (95% confidence
      interval 1.02-2.91) and SST errors (OR: 1.53 (1.14-2.07)] were associated with
      falls. After adjusting for other fall-risk factors in a multivariate logistic
      regression analysis, each error made during SST increased the odds of falling by
      a factor 1.7 [OR: 1.65 (1.17-2.34)]. CONCLUSIONS: this study shows the SST-a low
      cost video game device-is feasible for older people to undertake. The SST was
      able to distinguish fallers from non-fallers, providing a novel way to explore
      cognitive mechanisms for fall-risk in older people.

PMID- 24128594
TI  - Do people with dementia die at their preferred location of death? A systematic
      literature review and narrative synthesis.
AB  - AIM: place of death is an important component of the quality of a person's death.
      The aim of this study was to undertake a systematic review and narrative
      synthesis of the literature concerning place of death of people with dementia and
      the preferences for location of death of people with dementia as well as family
      carers and healthcare providers preferred location of death for patients with
      dementia. METHODS AND RESULTS: studies relying on death certificate data show
      that patients with dementia die more commonly in care homes than other locations
      contrasting with prospective studies which show that death is more common in own
      residence and hospital. Age (older), gender (male), availability of hospital and
      nursing home beds and enrolment in hospice, influence place of death. There is
      very limited evidence of patients, family carers and healthcare providers' views
      on preferred location of death for patients with dementia and the only study
      included reported that, family carers views are more agreed to rather than
      patients own views regarding place of death. CONCLUSION: this study on place of
      death raises exploratory questions on end-of-life care for patients with dementia
      which has implications on health and social care policies related to dementia.

PMID- 24128595
TI  - Single-agent liposomal all-trans-retinoic Acid as initial therapy for acute
      promyelocytic leukemia: 13-year follow-up data.

PMID- 24128596
TI  - [Medical-ethical review of multicenter studies can be obtained faster: new
      directive leaves room for improvement].
AB  - OBJECTIVE: To evaluate whether the speed at which multicenter studies can be
      launched in the Netherlands has been improved by the new External Review
      Directive. DESIGN: Cohort study. METHOD: We studied the time between requesting
      and granting a declaration of local feasibility of 7 multicenter studies under
      the new External Review Directive, which came into effect on 1 March 2012. We
      distinguished between centres that complied with the new directive and those that
      did not. We also compared the time to approval of local feasibility of these 7
      studies with those of 13 studies that were launched under the old directive.
      RESULTS: Under the new procedure, the median time between issue of the approval
      letter by the primary evaluative centre and approval by the Board of Directors of
      the participating centre was 93 days: 50 days for centres that performed the
      procedure in accordance with the directive (31 applications) and 118 days for
      centres that did not perform the review in accordance with the new directive (79
      applications). This difference was significant (log rank test; p = 0.003). Under
      the old procedure, the median time to approval was 103 days (336 applications).
      CONCLUSION: The new External Review Directive for multicenter studies provides a
      significant improvement in time to approval of local feasibility for multicenter
      trials in centres that commit to the new directive. However, the majority of
      hospitals have not yet complied with this directive, which still delays studies
      unnecessarily.

PMID- 24128597
TI  - [The behavioural variant of frontotemporal dementia: a challenging diagnosis].
AB  - We present the case of a 52-year-old man who was diagnosed with the behavioural
      variant of frontotemporal dementia (bvFTD) in accordance with consortium criteria
      from 1998. The diagnosis was questioned in the years of follow-up, since
      neuroimaging showed no abnormalities and no deterioration of clinical symptoms
      was seen. After 3 years, the diagnosis was withdrawn after the psychiatrist
      concluded that his low intelligence, combined with a cluster C personality and
      relational problems, had caused his altered behaviour. Diagnosing bvFTD is
      challenging because of its clinical resemblance to neurodegenerative and
      psychiatric illnesses. The new bvFTD consortium criteria from 2011 emphasize the
      importance of distinguishing possible and probable bvFTD. This can reduce the
      number of incorrect diagnoses. We present a flow chart based on these criteria,
      which could aid in improving the diagnostic process.

PMID- 24128598
TI  - [Mycoplasma-pneumoniae-associated mucositis].
AB  - BACKGROUND: The pathogen Mycoplasma pneumonia is a frequent cause of respiratory
      tract infections, especially in adolescents. Less well known is that this
      infection may also be associated with extrapulmonary manifestations including M.
      pneumonia associated mucositis (MPAM). CASE DESCRIPTION: A 19-year-old Dutch man
      was admitted to the hospital with severe mucositis, stomatitis, bilateral
      conjunctivitis, urethritis and mild exanthema on his arms. He had a one-week
      history of coughing and fever. Thorough microbiological investigations were
      implemented. After a few days both the IgM titre and polymerase chain reaction
      investigations for M. pneumonia from a throat swab taken on admission proved to
      be positive. Treatment with doxycycline resulted in rapid improvement in clinical
      condition. All mucosal lesions almost healed within two weeks. CONCLUSION: M.
      pneumonia infections may be associated with the triad of stomatitis,
      conjunctivitis and urethritis in the absence of extensive skin manifestations.
      The prognosis is favourable.

PMID- 24128599
TI  - [Trends in incidence of and mortality from ischaemic stroke].
AB  - OBJECTIVE: To investigate age- and sex-specific trends in incidence of and
      mortality from ischaemic stroke (IS) in the Netherlands. DESIGN: Descriptive
      study and cohort study. METHOD: Data from the cause-of-death statistics from
      Statistics Netherlands, the Dutch national medical registry and local council
      population registers were used. A cohort of IS patients was formed by linking
      these registers. Age- and sex-specific trends in mortality from IS in the period
      1980-2010 were determined using 'join point' regression analysis. The 30-day and
      1-year mortality rates following hospital admission for IS and the incidence of
      new cases of IS were calculated for the cohort of IS patients. Mann-Kendall tests
      were used for trend analysis over the period 1997-2005. RESULTS: Rates of
      mortality from IS decreased gradually in the period 1980-2000, with the exception
      of a levelling out of the rate of decrease in a few age groups in the 1990 s.
      Decrease in mortality declined dramatically after 2000 in all age groups, except
      for male patients in the age range 35-64 years. A comparative increased rate of
      decrease after 2000 was observed for 30-day and 1-year mortality following
      hospital admission for IS. The incidence of IS remained constant in the period
      1997-2005, or increased in a few age groups. CONCLUSION: Mortality rates
      following IS have decreased dramatically in the Netherlands since 2000. However,
      the number of cases of non-fatal IS has not decreased and is actually increasing
      slightly, indicating that more people have experienced IS. This is a concern,
      since IS often leads to disability with the accompanying burden of disease and
      economic burden. Prevention of IS is, therefore, extremely important.

PMID- 24128600
TI  - [Determination of brain death in organ donation: is EEG required?].
AB  - The determination of brain death is a prerequisite of multiple organ donation in
      ventilated patients in the ICU. The criteria for brain death differ
      internationally. In some countries, brain stem death is equivalent to brain
      death. In others, including the Netherlands, in addition to the determination of
      brain stem death, an EEG must also be carried out to rule out cortex activity
      according to the criteria of "whole brain death". However, this does not prove
      that there is complete failure of all brain functions; indeed, EEG does not
      examine the subcortical brain. The Dutch Health Board has established that brain
      death is ruled out by rest activity in the cortex, but not by persistent
      subcortical activity. This is conceptually incorrect. The criteria for brain stem
      death fit better in practice than the criteria for whole brain death. Taking an
      EEG should therefore no longer be an obligation in establishing brain death, as
      is the case in many other countries. 

PMID- 24128601
TI  - [Treating 'healthy' men who have localised cancer of the prostate].
AB  - In 2011, 11,428 men were diagnosed with prostate cancer in the Netherlands and
      2,500 men died from the disease. Since the introduction of the prostate specific
      antigen (PSA) measurements, few men have metastatic disease at the time
      diagnosis. More than half of prostate cancer patients are currently being
      diagnosed with low-volume localised prostate cancer. This raises the question
      whether all of these men should be treated, especially when prostate cancer
      specific mortality is low compared to overall mortality even in men without known
      comorbidity at the time of diagnosis. In recent series of such 'healthy' men
      treated for localised prostate cancer, the overall mortality exceeded prostate
      cancer mortality four to five-fold. Both tumour-related factors and general
      health status affect the outcome of prostate cancer treatment. In 'healthy' men
      with a low-volume, low-risk tumour, initial active surveillance is preferred
      above actual treatment. The small chance of progression and the possibility of
      curative treatment at the time of progression should be communicated to the
      patient. In men with an intermediate- or high-risk tumour, active treatment is
      preferred and depends on age and life expectancy. 

PMID- 24128602
TI  - [Health risks of airborne particulate matter in children].
AB  - The chemical composition of particulate matter can be very diverse, comprising a
      range of toxic compounds. Exposure to airborne particulate matter has been
      considered a substantial health risk for two decades now. There is no scientific
      evidence for a safe exposure limit. Therefore, current exposure levels across
      Europe are reason for concern. Exposure to particulate matter in adults may cause
      severe respiratory and cardiovascular disease. There is abundant epidemiological
      evidence that children, and younger children in particular, are more susceptible
      to the adverse effects of particular matter on health than adults. Short term
      exposure of children may already cause respiratory symptoms and allergic
      reactions. Environmental health policies reducing risks of exposure to
      particulate matter in children are recommended.

PMID- 24128603
TI  - The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis.
AB  - A vast and heterogeneous body of literature on the neuropsychology of obsessive
      compulsive disorder (OCD) has accumulated in recent decades, yielding
      inconsistent results. In an attempt to quantitatively summarize the literature,
      we conducted a meta-analysis of 115 studies (including 3452 patients), comparing
      adult OCD patients with healthy controls on tests of 10 neuropsychological
      domains. Across studies, medium mean effect sizes were found for all executive
      function subdomains, processing speed, and sustained attention. Small effect
      sizes were found for visuospatial abilities and working memory. A large effect
      size was found for non-verbal memory whereas a small effect size was found for
      verbal memory, where only the former was found to be associated with impairments
      in executive functions. Moderators of effect sizes were also investigated.
      Results are discussed in terms of their clinical significance as well as their
      implications for current neurobiological models of OCD and methodological
      caveats. 

PMID- 24128604
TI  - Magnetophoretic harvesting of oleaginous Chlorella sp. by using biocompatible
      chitosan/magnetic nanoparticle composites.
AB  - The consumption of energy and resources such as water in the cultivation and
      harvesting steps should be minimized to reduce the overall cost of biodiesel
      production from microalgae. Here we present a biocompatible and rapid
      magnetophoretic harvesting process of oleaginous microalgae by using chitosan
      Fe3O4 nanoparticle composites. Over 99% of microalgae was harvested by using the
      composites and the external magnetic field without changing the pH of culture
      medium so that it may be reused for microalgal culture without adverse effect on
      the cell growth. Depending on the working volume (20-500 mL) and the strength of
      surface magnetic-field (3400-9200 G), the process of harvesting microalgae took
      only 2-5 min. The method presented here not only utilizes permanent magnets
      without additional energy for fast harvesting but also recycles the medium
      effectively for further cultivation of microalgae, looking ahead to a large scale
      economic microalgae-based biorefinement.

PMID- 24128605
TI  - Subcritical CO2 pretreatment of sugarcane bagasse and its enzymatic hydrolysis
      for sugar production.
AB  - The present work investigated the effects of subcritical CO2 pretreatment of
      sugarcane bagasse at different CO2 pressure, pretreatment time, and temperature
      with relative high-solid concentration (15% w/v) to the composition of
      prehydrolyzate and the enzymatic hydrolysis. The results indicated that the
      maximum xylose yields in prehydrolyzate liquid were 15.78 g (combined 3.16 g
      xylose and 12.62 g xylo-oligosaccharides per 100g raw material). Due to the
      effective removal of hemicellulose, the maximum glucose yield in enzyme
      hydrolyzate reached 37.99 g per 100g raw material, representing 91.87% of glucose
      in the sugarcane bagasse. The maximal total sugars yield (combined xylose and
      glucose both in prehydrolyzate and enzymatic hydrolyzate) were 52.95 g based on
      100g raw material. These results indicated that subcritical CO2 pretreatment can
      effectively improve the enzymatic hydrolysis, so it could be successfully applied
      to sugarcane bagasse.

PMID- 24128606
TI  - Cationic surfactant-based method for simultaneous harvesting and cell disruption
      of a microalgal biomass.
AB  - Microalgae are one of the most promising sustainable energy sources for biodiesel
      production. However, the high costs of the downstream process are a major
      bottleneck for commercial-scale production of biodiesel from a microalgal
      biomass. A novel approach called the cationic surfactant-based harvesting and
      cell disruption (CSHD) method was studied to determine its effectiveness in
      simultaneous microalgal biomass harvesting and cell disruption. Using CSHD, the
      harvesting efficiency reached more than 91% in less than 5 min and 97% in 90 min.
      Moreover, CSHD exhibited a powerful ability to disrupt the cells; the lipid
      recovery was increased 133% compared to not using CSHD. CSHD allowed the
      extraction of up to 100% of the total lipids from a wet microalgal biomass with
      80% water content. All of these results were achieved without using energy
      intensive equipment. Altogether, our results suggest that CSHD is an energy
      efficient technique for the downstream process of microalgal lipid production.

PMID- 24128607
TI  - Association of body weight with the risk for malignancies in hospitalized
      patients with or without diabetes mellitus in Taiwan.
AB  - BACKGROUND: The purpose of this study was to determine the risk for cancers in
      patients with and without type 2 diabetes mellitus (DM) stratified by body mass
      index (BMI). METHODS: Patients hospitalized from January 2000 to December 2010
      with a diagnosis of malignant neoplasm (International Classification of Diseases,
      Ninth Revision, codes 140-208.91) were included. Diabetes mellitus was defined as
      a fasting blood glucose of 126 mg/dL or greater or a postprandial blood glucose
      of 200 mg/dL or greater. The patients were categorized according to BMI criteria
      for Asians: normal weight, BMI of less than 24 kg/m; overweight, BMI of greater
      than 24 kg/m; and obese, BMI of greater than 27 kg/m. RESULTS: A total of 42,229
      patients were included, of which 24,884 (59%) were normal weight, 10,096 (24%)
      were overweight, and 7,249 (17%) were obese. There were 4,195 (16.9%), 2,056
      (20.4%), and 1,625 (22.4%) patients with DM in the normal weight, overweight, and
      obese groups, respectively. Regardless of weight, the diabetic patients were more
      likely to have pancreas, liver, urinary tract, prostate, skin, hematological,
      lung, secondary, and gastric malignancies but were less likely to have cervical,
      oropharyngeal, nasopharyngeal, breast, or thyroid cancer. Regardless of sex or
      the presence or the absence of DM, the patients with more than 1 malignancy were
      more likely to die than were those with only 1 malignancy. Furthermore, the obese
      diabetic patients had higher mortality than did the obese nondiabetic patients
      with the same number of cancers. CONCLUSIONS: Regardless of weight category
      (normal, overweight, or obese), diabetic patients are more likely to have
      pancreas, liver, urinary tract, prostate, skin, hematological, lung, secondary,
      and gastric malignancies. Diabetic patients may benefit from increased
      surveillance for these cancers.

PMID- 24128608
TI  - A 104 kDa Aedes aegypti aminopeptidase N is a putative receptor for the Cry11Aa
      toxin from Bacillus thuringiensis subsp. israelensis.
AB  - The Cry11Aa protein produced in Bacillus thuringiensis subsp. israelensis, a
      bacterial strain used worldwide for the control of Aedes aegypti larvae, binds
      midgut brush border membrane vesicles (BBMV) with an apparent K(d) of 29.8 nM.
      Previously an aminopeptidase N (APN), named AaeAPN2, was identified as a putative
      Cry11Aa toxin binding protein by pull-down assays using biotinylated Cry11Aa
      toxin (Chen et al., 2009. Insect Biochem. Mol. Biol. 39, 688-696). Here we show
      this protein localizes to the apical membrane of epithelial cells in proximal and
      distal regions of larval caeca. The AaeAPN2 protein binds Cry11Aa with high
      affinity, 8.6 nM. The full-length and fragments of AaeAPN2 were cloned and
      expressed in Escherichia coli. The toxin-binding region was identified and
      further competitive assays demonstrated that Cry11Aa binding to BBMV was
      efficiently competed by the full-length AaeAPN2 and the fragments of AaeAPN2b and
      AaeAPN2e. In bioassays against Ae. aegypti larvae, the presence of full-length
      and a partial fragment (AaeAPN2b) of AaeAPN2 enhanced Cry11Aa larval mortality.
      Taken together, we conclude that AaeAPN2 is a binding protein and plays a role in
      Cry11Aa toxicity.

PMID- 24128609
TI  - Molecular characterization of the vitellogenin receptor from the tick, Amblyomma
      hebraeum (Acari: Ixodidae).
AB  - We have identified the full-length cDNA encoding a vitellogenin receptor (VgR)
      from the African bont tick Amblyomma hebraeum Koch (1844). VgRs are members of
      the low-density lipoprotein receptor superfamily that promote the uptake of the
      yolk protein vitellogenin (Vg), from the haemolymph. The AhVgR (GenBank accession
      No. JX846592) is 5703 bp, and encodes an 1801 aa protein with a 196.5 kDa
      molecular mass following cleavage of a 22 aa signal peptide. Phylogenetic
      analysis indicates that AhVgR is highly similar to other tick VgRs. AhVgR is
      expressed in only the ovary of mated, engorged females, and is absent in all
      other female tissues and in both fed and unfed males. Unfed, adult females
      injected with a VgR-dsRNA probe to knock-down VgR expression experienced a
      significant delay in ovary development and started oviposition significantly
      later than controls. These results indicate that the expression of AhVgR is
      important for the uptake of Vg and subsequent maturation of the oocytes. 

PMID- 24128610
TI  - Identification of the short neuropeptide F precursor in the desert locust:
      evidence for an inhibitory role of sNPF in the control of feeding.
AB  - Peptides of the short neuropeptide F (sNPF) family have been shown to modulate
      feeding behavior in a wide variety of insect species. While these peptides
      stimulate feeding and food-searching behavior in Drosophila melanogaster and Apis
      mellifera, an opposite effect has recently been demonstrated in the desert
      locust, Schistocerca gregaria. In this study, we elaborate on these observations
      with the identification of the nucleotide sequence encoding the Schgr-sNPF
      precursor and the study of its role in the regulation of locust feeding behavior.
      We confirm that both Schgr-sNPF-like peptides, previously identified in mass
      spectrometric studies, are genuine precursor-encoded peptides. RNA interference
      mediated silencing of the Schgr-sNPF precursor transcript generates novel
      evidence for an inhibitory role of Schgr-sNPF in the regulation of feeding in S.
      gregaria. Furthermore, we show that starvation reduces the Schgr-sNPF precursor
      transcript level in the optic lobes, the primary visual centers of the locust
      brain. Our data indicate that Schgr-sNPF exerts an inhibitory effect on food
      uptake in the desert locust, which contrasts with effects of sNPF reported for
      several other insect species. 

PMID- 24128611
TI  - Influence of additives to the formulation of n.c.a. [11C]PiB on sterile filter
      performance.
AB  - The influence of different additives (PEG 300, PEG 400, PG) to the product
      solution of [(11)C]PiB was investigated with regard to tracer retention for a
      number of commonly used sterile filters for aseptic manufacturing of PET-tracers.
      The effect of the amount of additive with regard to tracer retention and the
      resulting viscosity of the filtration solution was determined. Recommendations
      for the individual combinations of filters and amounts of additives suitable for
      the different filtration methods that are implemented in commercially available
      synthesis modules are given as well. 

PMID- 24128612
TI  - Prevalent combination of virulence and plasmidic-encoded resistance in ST 131
      Escherichia coli strains.
AB  - Escherichia coli ST131 is an important cause of multidrug-resistant infections.
      Thus, the aim of this study was to evaluate the concomitant presence of
      resistance plasmids and pathogenicity islands (PAIs) in ST131 E. coli. From 97
      extraintestinal E. coli characterized for antimicrobial susceptibility and
      extended-spectrum beta-lactamase production, 16% of isolates were identified as
      CTX-M-15 producers. These strains were studied by PFGE, MLST, and phylogroups,
      plasmid groups, PAIs, and plasmid-mediated quinolone-resistance determinants.
      MLST identified one ST10 strain from phylogroup A and the remaining isolates were
      ST131, from group B2. Despite the genetic variability, 64% of ST131 strains
      presented a profile composed by PAI IV536, PAI I(CFT073), and PAI II(CFT073),
      IncF plasmid, bla(CTX-M-15), and aac(6')-lb-cr genes. The prevalent virulence and
      resistance profile detected among the strains may constitute an optimal
      combination of factors, which allow E. coli ST131 to maintain both features
      becoming concomitantly virulent and extremely resistant.

PMID- 24128613
TI  - The response dynamics of preferential choice.
AB  - The ubiquity of psychological process models requires an increased degree of
      sophistication in the methods and metrics that we use to evaluate them. We
      contribute to this venture by capitalizing on recent work in cognitive science
      analyzing response dynamics, which shows that the bearing information processing
      dynamics have on intended action is also revealed in the motor system. This
      decidedly "embodied" view suggests that researchers are missing out on potential
      dependent variables with which to evaluate their models-those associated with the
      motor response that produces a choice. The current work develops a method for
      collecting and analyzing such data in the domain of decision making. We first
      validate this method using widely normed stimuli from the International Affective
      Picture System (Experiment 1), and demonstrate that curvature in response
      trajectories provides a metric of the competition between choice options. We next
      extend the method to risky decision making (Experiment 2) and develop predictions
      for three popular classes of process model. The data provided by response
      dynamics demonstrate that choices contrary to the maxim of risk seeking in losses
      and risk aversion in gains may be the product of at least one "online" preference
      reversal, and can thus begin to discriminate amongst the candidate models.
      Finally, we incorporate attentional data collected via eye-tracking (Experiment
      3) to develop a formal computational model of joint information sampling and
      preference accumulation. In sum, we validate response dynamics for use in
      preferential choice tasks and demonstrate the unique conclusions afforded by
      response dynamics over and above traditional methods. 

PMID- 24128614
TI  - New systems of care can leverage the health care workforce: how many doctors do
      we really need?
AB  - Improving access to appropriate health care, currently inadequate for many
      Americans, is more complex than merely increasing the projected number of
      physicians and nurses. Any attainable increase in their numbers will not solve
      the problem. To bring supply and demand closer, new systems of care are required,
      leveraging every member of the health care workforce, permitting professionals to
      provide their unique contributions.To increase supply: Redefine the roles of
      physicians and nurse practitioners (NPs), assess how much primary care must be
      delivered by a physician, and provide support from other team members to let the
      physician deal with complex patients. NPs can deliver much primary care and some
      specialty care. Care must be delivered in integrated systems permitting new
      payment models (e.g., salary with bonus) and team-based care as well as maximum
      use of electronic health records. Teams must make better use of nonprofessionals,
      such as Grand-Aides, using telephone protocols and portable telemedicine with
      home visits and online direct reporting of every encounter. The goals are to
      improve health and reduce unnecessary clinic and emergency department visits,
      admissions, and readmissions.To decrease demand: Physician payment must foster
      quality and appropriate patient volume (if accompanied by high patient
      satisfaction). Patients must be part of the team, work to remain healthy, and
      reduce inappropriate demand.The nation may not need as many physicians and nurses
      if the systems can be changed to promote integration, leveraging every member of
      the workforce to perform at his or her maximum competency. 

PMID- 24128615
TI  - The role of medical school culture in primary care career choice.
AB  - PURPOSE: To examine individual-level and medical-school-level factors, including
      the school's primary care culture, that are associated with medical students'
      likelihood of practicing primary care. METHOD: In spring 2010, the Association of
      American Medical Colleges Center for Workforce Studies invited all fourth-year
      medical students at a stratified random sample of 20 U.S. MD-granting medical
      schools to participate in an online survey examining factors in specialty choice
      decisions. Schools were stratified according to the historical percentage of
      their graduates who became practicing primary care physicians. Multilevel
      logistic regression modeling was used to determine which individual- and school
      level characteristics significantly predicted students' likelihood of practicing
      primary care. RESULTS: Of the 2,604 students invited, 1,661 (64%) responded. Of
      the 1,554 students with complete data on variables of interest, 207 (13%) planned
      to enter a primary care residency and stated they were "very likely" to become a
      primary care physician on completion of training. Students who attended schools
      with high reported levels of "badmouthing" primary care were less likely to
      practice primary care (OR, 0.6; 95% CI, 0.4-0.9). Attending a school where
      students had greater than the median number of positive experiences in primary
      care clerkships increased the likelihood of practicing primary care (OR, 1.6; 95%
      CI, 1.1-2.3). Overall, 8% of the total variation in a student's likelihood of
      practicing primary care was attributable to school-level factors. CONCLUSIONS:
      Although individual students' characteristics and preferences drive specialty
      choice decisions, the prevailing primary care culture at a school also plays a
      role.

PMID- 24128616
TI  - Innovative approaches to promote a culturally competent, diverse health care
      workforce in an institution serving Hispanic students.
AB  - The underrepresentation of minorities among health care providers and researchers
      is often considered one of the contributing factors to health disparities in
      these populations. Recent demographic shifts and the higher proportion of
      minorities anticipated among the newly insured under the Patient Protection and
      Affordable Care Act make the need for a more diverse and culturally competent
      health care workforce an urgent national priority.The authors describe current
      and future strategies that have been developed at the College of Health Sciences
      and Human Services at the University of Texas-Pan American (an institution with
      89% Hispanic students in 2012) to prepare a culturally competent and ethnically
      diverse health care workforce that can meet the needs of a diverse population,
      especially in the college's own community. The college graduates approximately
      650 students annually for careers in nursing, physician assistant studies,
      occupational therapy, pharmacy, rehabilitation services, clinical laboratory
      sciences, dietetics, and social work. The college's approach centers on enriching
      student education with research, service, and community-based experiences within
      a social-determinants-of-health framework. The approach is promoted through an
      interdisciplinary health disparities research center, multiple venues for
      community-based service learning, and an innovative approach to improve cultural
      and linguistic competence. Although the different components of the college's
      approach are at different developmental stages and will benefit from more formal
      evaluations, the college's overall vision has several strengths that promise to
      serve as a model for future academic health initiatives. 

PMID- 24128617
TI  - Academic medicine: a key partner in strengthening the primary care infrastructure
      via teaching health centers.
AB  - In the United States, a worsening shortage of primary care physicians, along with
      structural deficiencies in their training, threaten the primary care system that
      is essential to ensuring access to high-quality, cost-effective health care.
      Community health centers (CHCs) are an underused resource that could facilitate
      rapid expansion of the primary care workforce and simultaneously prepare trainees
      for 21st-century practice. The Teaching Health Center Graduate Medical Education
      (THCGME) program, currently funded by the Affordable Care Act, uses CHCs as
      training sites for primary-care-focused graduate medical education (GME).The
      authors propose that the goals of the THCGME program could be amplified by
      fostering partnerships between CHCs and teaching hospitals (academic medical
      centers [AMCs]). AMCs would encourage their primary care residency programs to
      expand by establishing teaching health center (THC) tracks. Modifications to the
      current THCGME model, facilitated by formal CHC and academic medicine
      partnerships (CHAMPs), would address the primary care physician shortage, produce
      physicians prepared for 21st-century practice, expose trainees to
      interprofessional education in a multidisciplinary environment, and facilitate
      the rapid expansion of CHC capacity.To succeed, CHAMP THCs require a
      comprehensive consortium agreement designed to ensure equity between the
      community and academic partners; conforming with this agreement will provide the
      high-quality GME necessary to ensure residency accreditation. CHAMP THCs also
      require a federal mechanism to ensure stable, long-term funding. CHAMP THCs would
      develop in select CHCs that desire a partnership with AMCs and have capacity for
      providing a community-based setting for both GME and health services research. 

PMID- 24128618
TI  - The migration of physicians and the local supply of practitioners: a five-year
      comparison.
AB  - PURPOSE: The overall distribution of physicians in the United States is uneven,
      with concentrations in urban areas while some rural places have proportionately
      very few. This report examines the movement of physicians who have completed
      their training and choose to move from one location to another. METHOD: The
      analysis linked the locations of practice of physicians practicing in the 50 U.S.
      states in 2006 and 2011 using data from the American Medical Association
      Physician Masterfile. Age, gender, location practice, activity status, and
      specialty were included in the data. Physicians who changed address in the five
      year period were identified and were compared with nonmovers using descriptive
      statistics. A summary logistic regression of movers compared with nonmovers was
      performed to assess the most important correlates of migration. RESULTS: The
      overall rate of county-to-county relocation for physicians was 19.8% for the five
      year period 2006-2011. Analyses indicated that older, male, and urban physicians
      were less likely to move; that physicians with osteopathic training were more
      likely to move; and that surgeons and primary care physicians were less likely to
      move compared with other specialists. CONCLUSIONS: The physician workforce in the
      United States migrates from place to place, and this movement determines the
      local supply of practitioners at any given time. Programs that intend to
      influence the local supply of doctors should account for this background tendency
      to relocate practice in order to achieve goals of more equal geographic
      distribution.

PMID- 24128619
TI  - The effects of expanding primary care access for the uninsured: implications for
      the health care workforce under health reform.
AB  - The Patient Protection and Affordable Care Act seeks to improve health equity in
      the United States by expanding Medicaid coverage for adults who are uninsured
      and/or socioeconomically disadvantaged; however, when millions more become
      eligible for Medicaid in 2014, the health care workforce and care delivery
      systems will be inadequate to meet the care needs of the U.S. population. To
      provide high-quality care efficiently to the expanded population of insured
      individuals, the health care workforce and care delivery structures will need to
      be tailored to meet the needs of specific groups within the population.To help
      create a foundation for understanding the use patterns of the newly insured and
      to recommend possible approaches to care delivery and workforce development, the
      authors describe the 13-year-old experience of the Virginia Coordinated Care
      program (VCC). The VCC, developed by Virginia Commonwealth University Health
      System in Richmond, Virginia, is a health-system-sponsored care coordination
      program that provides primary and specialty care services to patients who are
      indigent. The authors have categorized VCC patients from fiscal year 2011 by
      medical complexity. Then, on the basis of the resulting utilization data for each
      category over the next fiscal year, the authors describe the medical needs and
      health behaviors of the four different patient groups. Finally, the authors
      discuss possible approaches for providing primary, preventive, and specialty care
      to improve the health of the population while controlling costs and how adoption
      of the approaches might be shaped by care delivery systems and educational
      institutions. 

PMID- 24128620
TI  - Specializing in accountability: strategies to prepare a subspecialty workforce
      for care delivery redesign.
AB  - PROBLEM: Accountable care organizations (ACOs) emphasize cost-effectiveness,
      rewarding health care systems that provide the highest-quality care delivered by
      the most cost-efficient providers. Transitioning to an ACO model introduces
      distinct challenges for specialist physicians within academic health centers. As
      skin diseases constitute a large number of visits to primary care providers and
      specialists and place a significant financial burden on the health care system,
      the authors sought to identify specialist-driven strategies for cost-effective,
      patient-centered care delivery in dermatology. APPROACH: As part of the
      Massachusetts General Hospital's transition to an ACO, the Department of
      Dermatology in 2012 employed a team-based strategy to identify measures aimed at
      curbing the rate of rise in per-patient medical expense. Their approach may
      represent a methodological framework that translates to other specialist
      workforces. OUTCOMES: The authors identified four action areas: (1) rational,
      cost-conscious prescribing within therapeutic classes; (2) enhanced management of
      urgent access and follow-up appointment scheduling; (3) procedure
      standardization; and (4) interpractitioner variability assessment. They describe
      the practices implemented in these action areas, which include a mix of changes
      in both clinical decision making and operational practice and are aimed at
      improving overall quality and value of care delivery. They also offer
      recommendations for other specialty departments NEXT STEPS: Involving specialist
      physicians in care delivery redesign efforts provides unique insights to enhance
      quality, cost-effectiveness, and efficiency of care delivery. With increasing
      emphasis on ACO models, further specialist-driven strategies for ensuring patient
      centered delivery warrant development alongside other delivery reform efforts.

PMID- 24128621
TI  - Challenges and opportunities in building a sustainable rural primary care
      workforce in alignment with the Affordable Care Act: the WWAMI program as a case
      study.
AB  - The authors examine the potential impact of the Patient Protection and Affordable
      Care Act (ACA) on a large medical education program in the Northwest United
      States that builds the primary care workforce for its largely rural region. The
      42-year-old Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) program,
      hosted by the University of Washington School of Medicine, is one of the nation's
      most successful models for rural health training. The program has expanded
      training and retention of primary care health professionals for the region
      through medical school education, graduate medical education, a physician
      assistant training program, and support for practicing health professionals.The
      ACA and resulting accountable care organizations (ACOs) present potential
      challenges for rural settings and health training programs like WWAMI that focus
      on building the health workforce for rural and underserved populations. As more
      Americans acquire health coverage, more health professionals will be needed,
      especially in primary care. Rural locations may face increased competition for
      these professionals. Medical schools are expanding their positions to meet the
      need, but limits on graduate medical education expansion may result in a
      bottleneck, with insufficient residency positions for graduating students. The
      development of ACOs may further challenge building a rural workforce by limiting
      training opportunities for health professionals because of competing demands and
      concerns about cost, efficiency, and safety associated with training. Medical
      education programs like WWAMI will need to increase efforts to train primary care
      physicians and increase their advocacy for student programs and additional
      graduate medical education for rural constituents. 

PMID- 24128622
TI  - The emerging primary care workforce: preliminary observations from the primary
      care team: learning from effective ambulatory practices project.
AB  - Many primary care practices are changing the roles played by the members of their
      health care teams. The purpose of this article is to describe some of these new
      roles, using the authors' preliminary observations from 25 site visits to high
      performing primary care practices across the United States in 2012-2013. These
      sites visits, to practices using their workforce creatively, were part of the
      Robert Wood Johnson Foundation-funded initiative, The Primary Care Team: Learning
      From Effective Ambulatory Practices.Examples of these new roles that the authors
      observed on their site visits include medical assistants reviewing patient
      records before visits to identify care gaps, ordering and administering
      immunizations using protocols, making outreach calls to patients, leading team
      huddles, and coaching patients to set self-management goals. The registered nurse
      role has evolved from an emphasis on triage to a focus on uncomplicated acute
      care, chronic care management, and hospital-to-home transitions. Behavioral
      health providers (licensed clinical social workers, psychologists, or licensed
      counselors) were colocated and integrated within practices and were readily
      available for immediate consults and brief interventions. Physicians have shifted
      from lone to shared responsibility for patient panels, with other team members
      empowered to provide significant portions of chronic and preventive care.An
      innovative team-based primary care workforce is emerging. Spreading and
      sustaining these changes will require training both health professionals and
      nonprofessionals in new ways. Without clinical experiences that model this new
      team-based care and role models who practice it, trainees will not be prepared to
      practice as a team. 

PMID- 24128623
TI  - Physician assistants: from pipeline to practice.
AB  - For over four decades, physician assistants (PAs) have demonstrated that they are
      effective partners in a changing health care environment, readily adaptable to
      the needs of an evolving delivery system. With increased expectations of
      physician shortages, especially in primary care, PAs will be called on to fill
      provider gaps and new roles in interprofessional team-based delivery systems.
      There are over 90,000 certified PAs in the workforce and 173 accredited programs
      yielding an estimated 6,545 graduates annually, with an estimated 65 new programs
      seeking provisional accreditation by the end of 2016. New data on the PA pipeline
      and practice provide key information about the potential of this workforce;
      however, the overall impact of the PA pipeline on projected shortages remains
      unclear. Barriers exist to optimal deployment, including faculty shortages, scope
      of-practice regulations, and a lack of clinical placement sites.This article
      brings together data from the Physician Assistant Education Association and the
      National Commission on Certification of Physician Assistants and its supporting
      organization, the nccPA Health Foundation. Primary sources include PA candidates,
      educational programs, students, and certified PAs. Collectively, these data
      provide a comprehensive picture of PAs' contributions to the health care
      workforce. Armed with pipeline and graduate practice data, policy makers and
      workforce planners will be equipped to design new models of practice that
      maximize the potential contributions of this growing PA workforce on health care
      teams. 

PMID- 24128624
TI  - The role of academic health centers and their partners in reconfiguring and
      retooling the existing workforce to practice in a transformed health system.
AB  - Inspired by the Affordable Care Act and health care payment models that reward
      value over volume, health care delivery systems are redefining the work of the
      health professionals they employ. Existing workers are taking on new roles, new
      types of health professionals are emerging, and the health workforce is shifting
      from practicing in higher-cost acute settings to lower-cost community settings,
      including patients' homes. The authors believe that although the pace of health
      system transformation has accelerated, a shortage of workers trained to function
      in the new models of care is hampering progress. In this Perspective, they argue
      that urgent attention must be paid to retraining the 18 million workers already
      employed in the system who will actually implement system change.Their view is
      shaped by work they have conducted in helping practices transform care, by
      extensive consultations with stakeholders attempting to understand the workforce
      implications of health system redesign, and by a thorough review of the peer
      reviewed and gray literature. Through this work, the authors have become
      increasingly convinced that academic health centers (AHCs)-organizations at the
      forefront of innovations in health care delivery and health workforce training
      are uniquely situated to proactively lead efforts to retrain the existing
      workforce. They recommend a set of specific actions (i.e., discovering and
      disseminating best practices; developing new partnerships; focusing on systems
      engineering approaches; planning for sustainability; and revising credentialing,
      accreditation, and continuing education) that AHC leaders can undertake to
      develop a more coherent workforce development strategy that supports practice
      transformation. 

PMID- 24128625
TI  - The contribution of "plasticity" to modeling how a community's need for health
      care services can be met by different configurations of physicians.
AB  - This article introduces the concept of "plasticity" to health care workforce
      modeling and policy analysis. The authors define plasticity as the notion that
      individual physicians within the same specialty each provide a different scope of
      service, while the scope of service of physicians in different specialties may
      overlap. This notion represents a departure from the current, silo-based
      conception of physician supply as physician headcounts by specialty; the
      implication is that multiple configurations of physicians (and, by further
      application, other health care professionals) can meet a community's utilization
      of health care services.Within-specialty plasticity and between-specialty
      plasticity are two facets of plasticity. Within-specialty plasticity is the idea
      that individual physicians within the same specialty may each provide a different
      mix and scope of services, and between-specialty plasticity is the idea that
      patterns of service provision overlap across specialties. Changes in physician
      specialty supply in a community affect both the between-specialty and within
      specialty plasticity of that community's physicians. Notably, some physician
      specialties are more "plastic" than others.The authors demonstrate how to
      implement a plasticity matrix by assessing the sufficiency of physician supply in
      a specific community (Wayne County, North Carolina). Additional literature and
      data can provide further insights into the influences on (and of) plasticity,
      improving this approach and expanding it to include task-shifting across health
      care professions. 

PMID- 24128626
TI  - Selecting tomorrow's physicians: the key to the future health care workforce.
AB  - Recent U.S. health care reform efforts have focused on three main goals:
      improving health care for individuals, improving population health, and lowering
      costs. Physicians, who traditionally have practiced with considerable autonomy,
      will be required to become members of the team-based patient care models
      necessary to achieve these goals. In this perspective, the authors assert that
      medical school admissions, the selection of the future physician workforce, is a
      key component of health care reform. They review the historical context for
      medical school admission processes, which have placed a premium on grades and
      standardized test scores, and examine how admission practices are undergoing
      fundamental changes in order to select physicians with both the academic and
      interpersonal and intrapersonal competencies necessary to operate in the health
      care system of the future. The authors describe how new techniques, such as
      holistic review and multiple mini-interviews, are contributing to the shift
      toward competency-based medical education. Innovations underway at the
      Association of American Medical Colleges to transform medical school admissions
      also are explored. The authors conclude by arguing that although the admission
      process has great potential to transform the future health care workforce, major
      overhauls of the health care payment and delivery systems must be achieved
      alongside innovations in health professions education to truly transform the U.S.
      health care system. 

PMID- 24128627
TI  - Physician workforce planning in an era of health care reform.
AB  - Workforce planning in an era of health care reform is a challenge as both
      delivery systems and patient demographics change. Current workforce projections
      are based on a future health care system that is either an identified "ideal" or
      a modified version of the existing system. The desire to plan for such an "ideal
      system," however, may threaten access to necessary services if it does not come
      to fruition or is based on theoretical rather than empirical data.Historically,
      workforce planning that concentrated only on an "ideal system" has been centered
      on incorrect assumptions. Two examples of such failures presented in the 1980s
      when the Graduate Medical Education National Advisory Committee recommended a
      decrease in the physician workforce on the basis of predetermined "necessary and
      appropriate" services and in the 1990s, when planners expected managed care and
      health maintenance organizations to completely overhaul the existing health care
      system. Neither accounted for human behavior, demographic changes, and actual
      demand for health care services, leaving the nation ill-prepared to care for an
      aging population with chronic disease.In this article, the authors argue that
      workforce planning should begin with the current system and make adjustments
      based on empirical data that accurately reflect current trends. Actual health
      care use patterns will become evident as systemic changes are realized-or not
      over time. No single approach will solve the looming physician shortage, but the
      danger of planning only for an ideal system is being unprepared for the actual
      needs of the population. 

PMID- 24128628
TI  - Primary care teams: are we there yet? Implications for workforce planning.
AB  - Recent studies suggest that team-based primary care models could contribute to
      eliminating the predicted physician shortages. In this article, the authors
      explore existing team-based clinical care delivery models, comparing specialist
      and primary care teams, that include patient-centered medical homes and
      accountable care organizations. Next, the authors describe the barriers to
      adopting these models on a large scale, particularly the regulatory, financial,
      and cultural factors as well as scope of practice considerations for nonphysician
      providers. The authors' aim is not to evaluate the merits of team-based primary
      care models but, rather, to ascertain whether such models should be at the center
      of current physician workforce planning policies. The authors argue that although
      emerging evidence indicates that primary care teams can improve patient outcomes,
      few data exist to suggest that these models will drastically reduce the need for
      additional physicians or other providers. Thus, the authors conclude that
      additional research is needed to evaluate the ability of such models to alleviate
      provider deficits. And, while policy makers should work toward their ideal health
      care system, they also must expand the physician workforce to meet the growing
      demand for health care services in the existing one. 

PMID- 24128629
TI  - The military veteran to physician assistant pathway: building the primary care
      workforce.
AB  - The physician assistant (PA) profession emerged to utilize the skills of
      returning Vietnam-era military medics and corpsmen to fortify deficits in the
      health care workforce. Today, the nation again faces projected health care
      workforce shortages and a significant armed forces drawdown. The authors describe
      national efforts to address both issues by facilitating veterans' entrance into
      civilian PA careers and leveraging their skills.More than 50,000 service
      personnel with military health care training were discharged between 2006 and
      2010. These veterans' health care experience and maturity make them ideal
      candidates for civilian training as primary care providers. They trained and
      practiced in teams and functioned under minimal supervision to care for a broad
      range of patients. Military health care personnel are experienced in emergency
      medicine, urgent care, primary care, public health, and disaster medicine.
      However, the PA profession scarcely taps this valuable resource. Fewer than 4% of
      veterans with health care experience may ever apply for civilian PA training.The
      Health Resources and Services Administration (HRSA) implements two strategies to
      help prepare and graduate veterans from PA education programs. First, Primary
      Care Training and Enhancement (PCTE) grants help develop the primary care
      workforce. In 2012, HRSA introduced reserved review points for PCTE: Physician
      Assistant Training in Primary Care applicants with veteran-targeted activities,
      increasing their likelihood of receiving funding. Second, HRSA leads civilian and
      military stakeholder workgroups that are identifying recruitment and retention
      activities and curricula adaptations that maximize veterans' potential as PAs.
      Both strategies are described, and early outcomes are presented. 

PMID- 24128630
TI  - Exploring the workforce implications of a decade of medical school expansion:
      variations in medical school growth and changes in student characteristics and
      career plans.
AB  - PURPOSE: To explore whether medical school enrollment growth may help address
      workforce priorities, including diversity, primary care, care for underserved
      populations, and academic faculty. METHOD: The authors compared U.S. MD-granting
      medical schools, applicants, and matriculants immediately before expansion (1999
      2001) and 10 years later (2009-2011). Using data from the American Medical
      Association Physician Masterfile and the Association of American Medical
      Colleges, they examined medical schools' past production of physicians and
      changes in matriculant characteristics and practice intentions. RESULTS: Among
      the 124 schools existing in 1999-2001, growth varied substantially. Additionally,
      11 new schools enrolled students by 2009-2011. Aggregate enrollment increased by
      16.6%. Increases in applicants led to a lower likelihood of matriculation for all
      but those with rural backgrounds, racial/ethnic minorities, applicants >24 years
      old, and those with Medical College Admission Test scores > 33. The existing
      schools that expanded most had a history of producing the highest percentages of
      physicians practicing in primary care and in underserved and rural areas; those
      that expanded least had produced the greatest percentage of faculty. Compared
      with existing schools, new schools enrolled higher percentages of racial/ethnic
      minorities and of students with limited parental education or lower income.
      Matriculants' interest in primary care careers showed no decline; interest in
      practicing with underserved populations increased, while interest in rural
      practice declined. CONCLUSIONS: Despite expansion, the characteristics of
      matriculating medical students changed little, except at new schools. Further
      expansion may benefit from targeted consideration of workforce needs.

PMID- 24128631
TI  - Decreasing the length of residency training: a public policy perspective.
AB  - It is widely recognized that the United States is going to experience a serious
      shortage of physicians in the coming years unless the number of physicians
      completing residency training and entering practice is greatly increased. Members
      of the academic medicine community have approached this issue by calling on
      Congress to eliminate the cap that currently limits the number of residency
      positions that Medicare will support. Simply eliminating the cap, however, will
      not ensure an adequate supply of physicians. In this commentary the author argues
      that decreasing the length of training required in core clinical specialties will
      be required to effectively address the workforce shortage by allowing more
      residents to be trained in core specialties without greatly increasing the number
      of training programs and the aggregate amount that Medicare currently spends on
      graduate medical education. 

PMID- 24128632
TI  - A decade of rural physician workforce outcomes for the Rockford Rural Medical
      Education (RMED) Program, University of Illinois.
AB  - PURPOSE: To report on the retention and practice outcomes of the University of
      Illinois College of Medicine at Rockford Rural Medical Education (RMED) Program
      and to examine distance from influential locations in relation to graduates'
      current practice location. METHOD: The RMED Program recruits candidates from
      rural backgrounds, provides a supplemental curriculum addressing rural topics and
      experiences, and tracks graduates' practice location and specialty choice
      outcomes. Practice location and specialty were compared for 160 RMED graduates
      and 2,663 non-RMED graduates, from 1997 to 2007. Rural status was based on rural
      urban commuting codes. Comparisons were made using cross-tabulation with
      calculation of chi-square or odds ratios to assess differences. RESULTS: RMED
      graduates were 14.4 times more likely than non-RMED graduates to choose family
      medicine; 6.7 times more likely to choose a primary care practice specialty; 17.2
      times more likely to be currently practicing in a rural location; and 12.8 times
      more likely to be currently practicing in a primary care shortage zip code.
      Analysis of current RMED graduates' practice locations indicates that 41.9% were
      within 90 miles of their fourth-year preceptorship community. Among RMED
      graduates practicing in Illinois, 62.1% and 73.3% were located within 60 and 90
      miles, respectively, of their hometown. CONCLUSIONS: Recruitment of students
      combined with a rural-focused curriculum yielded positive outcomes related to
      primary care practice and decisions regarding practice location. RMED graduates
      were considerably more likely than non-RMED graduates to choose family medicine,
      choose a primary care specialty, and be currently practicing in a rural location.

PMID- 24128633
TI  - Raising the bar on achieving racial diversity in higher education: the United
      States Supreme Court's decision in Fisher v University of Texas.
AB  - In Fisher v University of Texas, the U.S. Supreme Court revisited the
      constitutionality of race-conscious admissions practices aimed at fostering
      student diversity in university programs. Although it concluded that student
      diversity remains the type of compelling state interest that justifies
      consideration of race in admissions, the court nonetheless raised the bar on the
      use of such practices by requiring universities to prove that no workable race
      neutral methods can produce the same result. Whether this standard of proof is
      one that can be met-and whether challenges will mount against universities that
      continue to use the holistic methods sanctioned 10 years ago in Grutter v
      Bollinger-remains to be seen. In this commentary, the authors review the
      background and history of the Supreme Court's decisions on race as a factor in
      university admissions decisions and examine the potential effects of Fisher on
      medical education specifically. 

PMID- 24128634
TI  - The role of private foundations in addressing health care workforce needs.
AB  - There is an increased awareness among policy makers, providers, and educators
      that the size, composition, geographic distribution, and skill mix of the health
      care workforce is of great importance in determining the likelihood of success in
      achieving our societal goals for health care reform. As academic and governmental
      institutions work to address these pressing questions, private foundations can
      and should play an important role in supporting the design, execution, and
      evaluation of innovative educational programs that will address these needs.
      Foundations also can and should play a role in generating information that will
      better inform health care workforce policies and in convening thought leaders to
      make recommendations that will advance the field of workforce studies.The author
      details current efforts by the Josiah Macy Jr. Foundation and other private
      foundations to address health care workforce needs. Foundations can play
      important roles as catalysts for change in our educational processes, and they
      can serve as important links between education and health care delivery systems.
      Partnerships among foundations and between private foundations and federal
      agencies can be powerful forces in helping to better align the skills of future
      health professionals with changing patient demographics and a changing health
      care system. 

PMID- 24128635
TI  - The changing meaning of a health care workforce.
AB  - In this commentary, the author describes how the meaning of the health care
      workforce has changed, focusing on the physician workforce. Some questions have
      been asked consistently over the years: How many should we have? What type? Where
      should they work? In 1830 there were no licensing laws, and every literate
      American could be a member of the health care workforce by following detailed
      instructions in a popular handbook. Subsequent years saw the initiation of state
      licensing laws and the reform of medical education. Medical specialties and
      specialty boards were created, although it was not until after World War II that
      the dominance of the general practitioner gave way to specialists. For over a
      century, estimates of physician supply have swung between "too many" and "too
      few." Rural and economically disadvantaged communities have long struggled with
      access to health care providers. The author also identifies some issues that have
      only been considered fairly recently, such as the ethnic and gender diversity of
      the workforce. Wars have played a major role in changing ideas about the
      workforce, often in ways that long outlast the actual dates of the conflict. The
      meaning of the health care workforce has always been deeply embedded in a
      specific social, political, and economic context. 

PMID- 24128636
TI  - Understanding the needs and concerns of senior faculty in academic medicine:
      building strategies to maintain this critical resource.
AB  - PURPOSE: The average age of medical school faculty is increasing, with 30% over
      age 55 in 2007. In 2012, 56% of Society of Teachers of Family Medicine (STFM)
      members were at least 50 years old. The authors sought to identify the transition
      and faculty development needs of this group of senior faculty. METHOD: In 2012
      the authors electronically surveyed 1,708 U.S. STFM members who were 50 or older,
      asking about demographics, highest degree, primary employer, career options
      considered in the previous year, issues of concern, mentoring needs, retirement
      plans, and likely activities in retirement. RESULTS: The response rate was 45%,
      with 73% MD/DOs, 62% men, 89% white, and 64% employed by academic institutions.
      The most frequent issues of concern were balancing personal and work time (67%),
      maintaining health (66%), and planning for retirement (60%). Nearly a third had
      considered career advancement, changing employers, or reducing full-time
      employment. Fifty-one percent were not receiving mentoring of any kind, but 47%
      reported they would like to have a mentor. Sixty-four percent were planning to
      retire; in retirement, 75% said they would like to remain active in teaching and
      55% in mentoring. CONCLUSIONS: Senior faculty in family medicine have significant
      career concerns and mentoring needs as they approach retirement, and these
      faculty can be valuable resources after retirement. As the age of faculty
      continues to rise, medical schools and specialty organizations can develop
      specific programs to meet the needs of these medical educators and better use
      this expertise in a time of limited resources.

PMID- 24128637
TI  - Going "all in" to transform the Tulsa community's health and health care
      workforce.
AB  - Oklahoma's health status ranks among the lowest of the states', yet many
      Oklahomans oppose the best-known aspects of federal health reform legislation. To
      address this situation, the University of Oklahoma College of Medicine's School
      of Community Medicine in Tulsa adopted an "all-in," fully committed approach to
      transform the Tulsa region's health care delivery system and health care
      workforce teaching environment by leading community-wide initiatives that took
      advantage of lesser-known health reform provisions. Medical school leaders shared
      a vision of improved health for the region with a focus on equity in care for
      underserved populations. They engaged Tulsa stakeholders to implement health
      system changes to improve care access, quality, and efficiency. A partnership
      between payers, providers, and health systems transformed primary care practices
      into patient-centered medical homes (PCMHs) and instituted both community-wide
      care coordination and a regional health information exchange. To emphasize the
      importance of these new approaches to improving the health of an entire
      community, the medical school began to transform the teaching environment by
      adding several interdependent experiences. These included an annual
      interdisciplinary summer institute in which students and faculty from across the
      university could explore firsthand the social determinants of health as well as
      student-run PCMH clinics for the uninsured to teach systems-based practice, team
      based learning, and health system improvement. The authors share lessons learned
      from these collaborations. They conclude that working across competitive
      boundaries and going all in are necessary to improve the health of a community. 

PMID- 24128638
TI  - State patterns in medical school expansion, 2000-2010: variation, discord, and
      policy priorities.
AB  - In 2006, the Association of American Medical Colleges recommended a 30% increase
      over 2002 enrollment in U.S. medical schools by the year 2016, particularly in
      areas with rapid population growth during the past 25 years or where the
      population was projected to grow rapidly in future years. Both MD-granting and DO
      granting schools subsequently expanded enrollment. To examine the relationship
      between ongoing medical school expansion and state-level measures of population
      need and workforce capacity, the authors used established national health
      workforce and training site datasets to compare total medical school enrollment
      (2000-2010) with change in population, medical student retention in state (those
      returning to practice in the state where they graduated), and primary care
      supply.From 2000 to 2010, U.S. population increased 10% (median state population
      growth 7.4%). Median state total MD and DO medical school enrollment growth was
      14.7%, with nine states increasing enrollment by more than 50%. Medical student
      retention rates varied from 9.8% to 67%. A wide variation in concordance and
      discordance between medical school enrollment to population growth and to medical
      student retention rates existed across states. States also demonstrated
      concordance or discordance between medical school enrollment and supply of
      primary care physicians.The authors recommend strategies for expansion that may
      help meet the population's need for primary care physicians and improved
      geographic distribution of specialties. Expansion of graduate medical education
      must also be aligned with population need, necessitating coordination of
      workforce planning. 

PMID- 24128639
TI  - How many doctors will we need? A special issue on the physician workforce.

PMID- 24128640
TI  - Do residents who train in safety net settings return for practice?
AB  - PURPOSE: To examine the relationship between training during residency in a
      federally qualified health center (FQHC), rural health clinic (RHC), or critical
      access hospital (CAH) and subsequent practice in these settings. METHOD: The
      authors identified residents who trained in safety net settings from 2001 to 2005
      and in 2009 using 100% Medicare Part B claims files for FQHCs, RHCs, and CAHs and
      2011 American Medical Association Masterfile residency start and end date
      histories. They used 2009 Medicare claims data to determine the relationship
      between this training and subsequent practice in safety net settings. RESULTS:
      The authors identified 662 residents who had a Medicare claim filed in their name
      by an RHC, 975 by an FQHC, and 1,793 by a CAH from 2001 to 2005 and in 2009. By
      2009, that number of residents per year had declined for RHCs and FQHCs but
      increased substantially for CAHs. The percentage of physicians practicing in a
      safety net setting in 2009 who had trained in a similar setting from 2001 to 2005
      was 38.1% (205/538) for RHCs, 31.2% (219/703) for FQHCs, and 52.6% (72/137) for
      CAHs. CONCLUSIONS: Using Medicare claims data, the authors identified residents
      who trained in safety net settings and demonstrated that many went on to practice
      in these settings. They recommend that graduate medical education policy support
      or expand training in these settings to meet the surge in health care demand that
      will occur with the enactment of the Affordable Care Act insurance provision in
      2014.

PMID- 24128641
TI  - AM last page: medical students' plans at graduation and their relationship with
      actual practice.

PMID- 24128642
TI  - Restructuring medical education to meet current and future health care needs.
AB  - U.S. health care is changing, and it will continue to change across multiple
      dimensions: a different mix of patients; more ambulatory, chronic care and less
      acute, inpatient care; an older population; expanded insurance coverage; a team
      approach to care; rapid growth of subspecialty care; growing emphasis on cost
      effective care; and rapid technological change. These changes demand a
      corresponding evolution in physician roles and training. However, despite
      innovation in content and teaching methods, there has been little alteration to
      the basic structure of medical education since the Flexner Report sparked
      widespread reform in 1910. Looking to the future, medical education might evolve
      to include preparation for a team approach to care via practical training for
      multispecialty collaborative practice and preparing physicians to be leaders of
      primary care teams that include nonphysician providers; shorter training for some
      physicians via flexible pathways and "fast tracks" at each phase of training;
      cost-effective care in clinical practice; increased training in geriatrics; and
      "on ramps" and "off ramps" along the physician career path for flexible training
      over a lifetime. Although the challenges facing the health care system are great,
      meeting changing health care needs must begin at the foundation, in medical
      education. 

PMID- 24128643
TI  - Feelings of rewards among family caregivers during ongoing palliative care.
AB  - OBJECTIVES: Palliative family caregivers appear to experience the rewards of
      caregiving concurrent with burdens and negative feelings. Relatively few studies
      have attended to the positive and rewarding aspects in palliative family
      caregiving. In addition, most studies on rewards are retrospective and examine
      the experiences of bereaved family caregivers. The present study aimed at
      describing feelings of reward among family caregivers during ongoing palliative
      care. A further aim was to compare the experience of rewards in relation to sex
      and age. METHODS: The sample consisted of 125 family caregivers and took place in
      three specialist palliative care units and one hematology unit. Participants
      answered a questionnaire including demographic background questions and the
      Rewards of Caregiving Scale (RCS). Descriptive statistics were employed to
      describe characteristics of the participants and the level of rewards. A Mann
      Whitney U test was used to compare differences between groups of different sex
      and age. RESULTS: Palliative family caregivers reported general high levels of
      reward. The greatest source of rewards involved feelings of being helpful to
      patients. This was closely followed by giving something to patients that brought
      them happiness and being there for them. The smallest sources of rewards were
      related to personal growth, self-satisfaction, and personal meaning. There was
      also an association between rewards and age but not between men and women.
      SIGNIFICANCE OF RESULTS: Family caregivers experienced the rewards of caregiving
      during ongoing palliative care despite their unique and stressful situation.
      Feelings of reward seem to be about handling a situation in a satisfying way,
      feeling competent and confident to take care of the patient and thereby feeling
      proud. Support could preferably be designed to improve a family caregiver's
      ability to care and to facilitate the positive aspects and rewards of caregiving
      and focus on strengths and resources.

PMID- 24128644
TI  - Prediction of the optimal time for insemination using frozen-thawed semen in a
      multi-sire insemination trial in bitches.
AB  - The aims of the study were to determine which of Days 5, 6 or 7 after the blood
      plasma progesterone concentration (PPC) of bitches first reached 6-9 nmol/L (Day
      0) yield the highest fertility and whether day of insemination affects the gender
      ratio of conceptuses. Six bitches were inseminated on Days 5 and 6 and 6 on Days
      6 and 7. Ten million progressively motile frozen-thawed sperm from each of 5 dogs
      were pooled for the first insemination. The same number of sperm from 5 other
      dogs were pooled for the second insemination. Only one batch of semen from each
      dog was used on all bitches, which largely prevented any effect of male and
      semen. Twenty-three autosomal microsatellites and the amelogenin gene were used
      to determine the paternity and gender of the conceptuses. Pregnancy rate was
      100%. Out of 103 ovulations 66 conceptuses were conceived (conception rate: 64%).
      The proportion of available oocytes fertilised was 0.11, 0.56, and 0.27 for Days
      5, 6, and 7, respectively. The odds of fertilisation was 16.7 and 4.2 times
      higher from insemination on Day 6 compared to Day 5 (P<0.001) and Day 7 (P =
      0.013), respectively. The numbers of male- and female conceptuses were equal (33
      each) and gender was independent of insemination day (P = 0.18). This study
      suggests that intrauterine insemination of bitches should best be done 6 days
      after PPC first reaches a value between 6 and 9 nmol/L with a second insemination
      one day later.

PMID- 24128645
TI  - Not simply synthetic tetrahydrocannabinol.

PMID- 24128646
TI  - Reply: To PMID 23391041.

PMID- 24128647
TI  - Pediatric abdominal radiograph use, constipation, and significant misdiagnoses.
AB  - OBJECTIVE: To determine the proportion of children diagnosed with constipation
      assigned a significant alternative diagnosis within 7 days (misdiagnosis), if
      there is an association between abdominal radiograph (AXR) performance and
      misdiagnosis, and features that might identify children with misdiagnoses. STUDY
      DESIGN: We conducted a retrospective cohort study of consecutive children <18
      years who presented to a pediatric emergency department in Toronto, between 2008
      and 2010. Children assigned an International Statistical Classification of
      Diseases and Related Health Problems 10th Revision code consistent with
      constipation were eligible. Misdiagnosis was defined as an alternative diagnosis
      during the subsequent 7 days that resulted in hospitalization or an outpatient
      procedure that included a surgical or radiologic intervention. Constipation
      severity was classified employing text word categorization and the Leech score.
      RESULTS: 3685 eligible visits were identified. Mean age was 6.6 +/- 4.4 years.
      AXR was performed in 46% (1693/3685). Twenty misdiagnoses (0.5%; 95% CI 0.4, 0.8)
      were identified (appendicitis [7%], intussusception [2%, bowel obstruction [2%],
      other [9%]). AXR was performed more frequently in misdiagnosed children (75% vs
      46%; P = .01). These children more often had abdominal pain (70% vs 49%; P = .04)
      and tenderness (60% vs 32%; P =.01). Children in both groups had similar amounts
      of stool on AXR (P = .38) and mean Leech scores (misdiagnosed = 7.9 +/- 3.4; not
      misdiagnosed = 7.7 +/- 2.9; P = .85). CONCLUSIONS: Misdiagnoses in children with
      constipation are more frequent in those in whom an AXR was performed and those
      with abdominal pain and tenderness. The performance of an AXR may indicate
      diagnostic uncertainty; in such cases, the presence of stool on AXR does not rule
      out an alternative diagnosis.

PMID- 24128649
TI  - Standardization of pediatric headache evaluation and treatment in the emergency
      department.

PMID- 24128648
TI  - Molecular epidemiology of Staphylococcus aureus in households of children with
      community-associated S aureus skin and soft tissue infections.
AB  - OBJECTIVES: Although colonization traditionally is considered a risk factor for
      Staphylococcus aureus infection, the relationship between contemporary S aureus
      colonization and infection is not well characterized. We aimed to relate the
      presence of colonizing and disease-causing strains of S aureus within individuals
      and households. STUDY DESIGN: In a prospective study of 163 pediatric outpatients
      (cases) with community-associated S aureus skin and soft tissue infections in St
      Louis, infection isolates were obtained from cases and colonization cultures were
      obtained from cases and their household contacts (n = 562). Molecular typing by
      repetitive sequence-based polymerase chain reaction was used to compare infecting
      and colonizing isolates within each case. The infecting strain from each case was
      compared with S aureus strains colonizing household contacts. The colonization
      status of cases was followed for 12 months. RESULTS: A total of 27 distinct
      strain types were identified among the 1299 S aureus isolates evaluated. Between
      1 and 6 distinct strain types were detected per household. A total of 110 cases
      (67%) were colonized at 1 or more body sites with the infecting strain. Of the 53
      cases with an infecting strain that did not match a colonizing strain, 15 (28%)
      had 1 or more household contacts with a colonizing strain that matched the
      infecting strain. Intrafamilial strain-relatedness was observed in 105 families
      (64%). CONCLUSION: One-third of cases were colonized with a different strain type
      than the strain causing the skin and soft tissue infection. Fewer than one-third
      of cases with discordant infecting and colonizing isolates could be linked to the
      strain from another household contact, suggesting acquisition from sources
      outside the household.

PMID- 24128650
TI  - Nausea predicts delayed gastric emptying in children.
AB  - OBJECTIVES: To assess whether the gastroparesis cardinal symptom index (GCSI), or
      any individual symptom, is associated with delayed gastric emptying in children,
      and to assess understanding of symptoms associated with delayed gastric emptying.
      STUDY DESIGN: Fifty children (36 F), 5-18 years of age, undergoing gastric
      emptying scintigraphy (GES) at Lurie Children's Hospital in Chicago, Illinois,
      completed Likert-type GCSI and symptom comprehension questionnaires. Correlation
      of GES results (normal or abnormal) with questionnaire results using the Wilcoxon
      rank sum test. RESULTS: Seventy percent of subjects had a normal GES. Children
      reported understanding most terms of GCSI (average score 2.59, range 0-3). The
      GCSI was not associated with delayed gastric emptying. Nausea was associated with
      delayed gastric emptying only (numerical P = .04, word P = .02). Results were not
      altered when poorly understood terms were excluded. CONCLUSIONS: The GCSI is not
      associated with delayed gastric emptying in children. Lack of association does
      not seem to be related to lack of understanding. Nausea alone was the only
      symptom that showed an association with delayed gastric emptying on GES.

PMID- 24128652
TI  - Radiation optic neuropathy after proton beam therapy for optic nerve sheath
      meningioma.

PMID- 24128651
TI  - Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and
      infectious diseases.
AB  - Nanocarriers with various compositions and biological properties have been
      extensively applied for in vitro/in vivo drug and gene delivery. The family of
      nanocarriers includes polymeric nanoparticles, lipid-based carriers
      (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles
      (nanoshells/nanocages). Among different delivery systems, polymeric carriers have
      several properties such as: easy to synthesize, inexpensive, biocompatible,
      biodegradable, non-immunogenic, non-toxic, and water soluble. In addition,
      cationic polymers seem to produce more stable complexes led to a more protection
      during cellular trafficking than cationic lipids. Nanoparticles often show
      significant adjuvant effects in vaccine delivery since they may be easily taken
      up by antigen presenting cells (APCs). Natural polymers such as polysaccharides
      and synthetic polymers have demonstrated great potential to form vaccine
      nanoparticles. The development of new adjuvants or delivery systems for DNA and
      protein immunization is an expanding research field. This review describes
      polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery
      systems. 

PMID- 24128653
TI  - Energy metabolism of cerebral mitochondria during aging, ischemia and post
      ischemic recovery assessed by functional proteomics of enzymes.
AB  - Stroke is a leading cause of death and disability, but most of the therapeutic
      approaches failed in clinical trials. The energy metabolism alterations, due to
      marked ATP decline, are strongly related to stroke and, at present, their
      physiopathological roles are not fully understood. Thus, the aim of this study
      was to evaluate the effects of aging on ischemia-induced changes in energy
      mitochondrial transduction and the consequences on overall brain energy
      metabolism in an in vivo experimental model of complete cerebral ischemia of
      15min duration and during post-ischemic recirculation after 1, 24, 48, 72 and
      96h, in 1year "adult" and 2year-old "aged" rats. The maximum rate (Vmax) of
      citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle;
      NADH-cytochrome c reductase and cytochrome oxidase for electron transfer chain
      (ETC) were assayed in non-synaptic "free" mitochondria and in two populations of
      intra-synaptic mitochondria, i.e., "light" and "heavy" mitochondria. The
      catalytic activities of enzymes markedly differ according to: (a) mitochondrial
      type (non-synaptic, intra-synaptic), (b) age, (c) acute effects of ischemia and
      (d) post-ischemic recirculation at different times. Enzyme activities changes are
      injury maturation events and strictly reflect the bioenergetic state of the
      tissue in each specific experimental condition respect to the energy demand, as
      shown by the comparative evaluation of the energy-linked metabolites and
      substrates content. Remarkably, recovery of mitochondrial function was more
      difficult for intra-synaptic mitochondria in "aged" rats, but enzyme activities
      of energy metabolism tended to normalize in all mitochondrial populations after
      96h of recirculation. This observation is relevant for Therapy, indicating that
      mitochondrial enzymes may be important metabolic factors for the responsiveness
      of ischemic penumbra towards the restore of cerebral functions. 

PMID- 24128655
TI  - Takotsubo cardiomyopathy: an integrated multi-imaging approach.
AB  - Takotsubo cardiomyopathy (TTC) is a distinct clinical entity characterized by the
      presence of transient left ventricular wall dysfunction without significant
      culprit obstructive coronary artery disease. Invasive coronary angiography and
      ventriculography are the 'gold standard' for definitive diagnosis, with an
      integrated multi-modality imaging approach offering advantages in various
      clinical scenarios. Echocardiography is a widely available, first-line, non
      invasive imaging technique appropriate both in emergency setting to confirm
      diagnosis, assess for various potential acute complications, and in serial follow
      up to track myocardial recovery. Cardiac magnetic resonance (CMR) may be helpful
      to discriminate TTC from other acute cardiac syndromes with troponin elevation
      and ventricular dysfunction. Echocardiography, CMR, and nuclear imaging may also
      provide new insights into possible underlying pathophysiological mechanisms, and
      myocardial (123)I-metaiodobenzyl-guanidine imaging may have a role for
      retrospective diagnosis in the subacute phase of late-presenting cases. The
      potential diagnostic role of coronary computed tomography angiography in the
      emergency room requires a further study. 

PMID- 24128654
TI  - Effect of salmon consumption during pregnancy on maternal and infant faecal
      microbiota, secretory IgA and calprotectin.
AB  - The gut microbiota plays an important role in the development of the immune and
      gastrointestinal systems of infants. In the present study, we investigated
      whether increased salmon consumption during pregnancy, maternal weight gain
      during pregnancy or mode of infant feeding alter the markers of gut immune
      defence and inflammation. Women (n 123) who rarely ate oily fish were randomly
      assigned to continue consuming their habitual diet or to consume two 150 g
      portions of farmed salmon per week from 20 weeks of pregnancy to delivery. Faecal
      samples were collected from the mothers (n 75) at 38 weeks of gestation and from
      their infants (n 38) on days 7, 14, 28 and 84 post-partum. Fluorescence in situ
      hybridisation was used to determine faecal microbiota composition and ELISA to
      measure faecal secretory IgA (sIgA) and calprotectin concentrations. There was no
      effect of salmon consumption on maternal faecal microbiota or on maternal or
      infant faecal sIgA and calprotectin concentrations. The degree of weight gain
      influenced maternal faecal microbiota, and the mode of infant feeding influenced
      infant faecal microbiota. Faecal samples collected from infants in the salmon
      group tended to have lower bacterial counts of the Atopobium cluster compared
      with those collected from infants in the control group (P=0.097). This difference
      was significant in the formula-fed infants (P< 0.05), but not in the exclusively
      breast-fed infants. In conclusion, the impact of oily fish consumption during
      pregnancy on maternal and infant gut microbiota composition is limited, but
      significant differences are associated with maternal weight gain during pregnancy
      and mode of infant feeding.

PMID- 24128656
TI  - Low shear stress up-regulation of proinflammatory gene expression in human
      retinal microvascular endothelial cells.
AB  - The vascular endothelium responds to shear stress generated by blood flow and
      changes functions to regulate blood flow and maintain tissue homeostasis.
      Recently, we found that arteriolar high shear stress leads to increased
      expression of vasodilatory and antithrombotic genes in human retinal
      microvascular endothelial cells (HRMECs). However, it is unknown whether low
      shear stress, which is induced by hypoperfusion particularly in the retinal
      venules where leukocyte-endothelial interactions mainly occur, affects the
      retinal endothelial function. We studied the effect of low shear stress on
      proinflammatory gene expression in HRMECs. The cells were cultured on glass
      plates and exposed to laminar shear stresses of 0 (static), 1.5 (relatively low
      flow), and 15 dyne/cm(2) (relatively high flow) for 24 h using parallel plate
      type flow-loading devices. The mRNA expressions of adhesion molecules, cytokines
      and chemokines, and procoagulant factors were evaluated using real-time reverse
      transcription polymerase chain reaction. HRMECs exposed to 1.5 dyne/cm(2)
      significantly up-regulated the mRNA expression of intercellular adhesion molecule
      1, vascular cell adhesion molecule-1, and E-selectin. The cells exposed to 1.5
      dyne/cm(2) of stress also had increased cytokine/chemokine mRNA expression, i.e.,
      interleukin (IL)-6, IL-8, platelet-derived growth factor-B, and monocyte
      chemotactic protein-1. Procoagulant factors, i.e., tissue factor and plasminogen
      activator inhibitor-1 mRNA, increased significantly with exposure to 1.5
      dyne/cm(2) of stress. Our results showed that relatively low shear stress causes
      up-regulation of proinflammatory genes in HRMECs, suggesting that decreased shear
      stress due to vascular hypoperfusion might change the phenotypic characterization
      of the retinal vascular endothelium and be associated with leukocyte-endothelial
      interactions. 

PMID- 24128657
TI  - Neural processing of intentional biological motion in unaffected siblings of
      children with autism spectrum disorder: an fMRI study.
AB  - Despite often showing behaviorally typical levels of social cognitive ability,
      unaffected siblings of children with autism spectrum disorder have been found to
      show similar functional and morphological deficits within brain regions
      associated with social processing. They have also been reported to show increased
      activation to biological motion in these same regions, such as the posterior
      superior temporal sulcus (pSTS), relative to both children with autism and
      control children. It has been suggested that this increased activation may
      represent a compensatory reorganization of these regions as a result of the
      highly heritable genetic influence of autism. However, the response patterns of
      unaffected siblings in the domain of action perception are unstudied, and the
      phenomenon of compensatory activation has not yet been replicated. The present
      study used functional magnetic resonance imaging to determine the neural
      responses to intentional biological actions in 22 siblings of children with
      autism and 22 matched controls. The presented actions were either congruent or
      incongruent with the actor's emotional cue. Prior studies reported that typically
      developing children and adults, but not children with autism, show increased
      activation to incongruent actions (relative to congruent), within the pSTS and
      dorsolateral prefrontal cortex. We report that unaffected siblings did not show a
      compensatory response, or a preference for incongruent over congruent trials, in
      any brain region. Moreover, interaction analyses revealed a sub-region of the
      pSTS in which control children showed an incongruency preference to a
      significantly greater degree than siblings, which suggests a localized deficit in
      siblings. A sample of children with autism also did not show differential
      activation in the pSTS, providing further evidence that it is an area of
      selective disruption in children with autism and siblings. While reduced
      activation to both conditions was unique to the autism sample, lack of
      differentiation to incongruent and congruent intentional actions was common to
      both children with ASD and unaffected siblings. 

PMID- 24128658
TI  - Toward a mental arithmetic process in risky choices.
AB  - Mainstream theories about decision-making under risk suggest that risky decisions
      are made by choosing the option that offers the highest mathematical expectation.
      The present event-related potentials (ERPs) study investigated the neurocognitive
      mechanisms underlying risky choice by contrasting a preferential choice task with
      an expected value choice task. The ERP data revealed that (1) the computational
      difficulty, which would be expected to influence a compensatory process, affected
      the slow wave only when participants were forced to choose the option with the
      highest expectation; and that (2) the difference in the minimum outcome dimension
      between two options, which would be expected to be influential in a heuristic
      process, affected the P300 and slow wave when participants were asked to choose
      the preferred option. Our findings provide neural evidence that preferential
      choice is not based on an expectation computation and thus raised the question of
      whether expectation theories can provide an adequate description of individual
      risky decisions. 

PMID- 24128659
TI  - Examining the link between adolescent brain development and risk taking from a
      social-developmental perspective.
AB  - The adolescent age period is often characterized as a health paradox because it
      is a time of extensive increases in physical and mental capabilities, yet overall
      mortality/morbidity rates increase significantly from childhood to adolescence,
      often due to preventable causes such as risk taking. Asynchrony in developmental
      time courses between the affective/approach and cognitive control brain systems,
      as well as the ongoing maturation of neural connectivity are thought to lead to
      increased vulnerability for risk taking in adolescence. A critical analysis of
      the frequency of risk taking behaviors, as well as mortality and morbidity rates
      across the lifespan, however, challenges the hypothesis that the peak of risk
      taking occurs in middle adolescence when the asynchrony between the different
      developmental time courses of the affective/approach and cognitive control
      systems is the largest. In fact, the highest levels of risk taking behaviors,
      such as alcohol and drug use, often occur among emerging adults (e.g.,
      university/college students), and highlight the role of the social context in
      predicting risk taking behavior. Moreover, risk taking is not always unregulated
      or impulsive. Future research should broaden the scope of risk taking to include
      risks that are relevant to older adults, such as risky financial investing,
      gambling, and marital infidelity. In addition, a lifespan perspective, with a
      focus on how associations between neural systems and behavior are moderated by
      context and trait-level characteristics, and which includes diverse samples
      (e.g., divorced individuals), will help to address some important limitations in
      the adolescent brain development and risk taking literature. 

PMID- 24128660
TI  - Design, synthesis and binding affinity of acetylcholine carbamoyl analogues.
AB  - A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety
      or at the cationic head or at both, were tested for binding affinity at
      muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic
      affinity was found, submicromolar Ki values, similar to that of carbachol, were
      measured at alpha4beta2 nAChRs for the enantiomers of 5-dimethylaminomethyl- and
      5-trimethylammoniomethyl-2-oxazolidinone, 2 and 2a, and for (S)-N-methylprolinol
      carbamate (S)-3. Methylation of oxazolidinone nitrogen of 2 and 2a and of N
      methylprolinol nitrogen of (S)-3 and, even more, hybridization of cyclic
      carbamate substructure (oxazolidinone) with cyclic cationic head (N
      methylpyrrolidine) markedly lower the nicotinic affinity. Docking results were
      consistent with SAR analysis highlighting the interaction capabilities of (R)-2a
      and (S)-3 and the negative effect of intracyclic nitrogen methylation and of
      double cyclisation. 

PMID- 24128661
TI  - Living with clipped wings-patients' experience of losing a leg.
AB  - This study explores the lived experience of losing a leg as described by the
      patients themselves post-discharge. Studies have documented that regardless of
      aetiology patients are faced with severe physical as well as psychosocial
      challenges post-amputation. However, only few studies explore in-depth the
      patients' perspective on the various challenges following the loss of a leg. The
      study uses the phenomenological approach of Reflective Lifeworld Research (RLR).
      Data were collected from 24 in-depth interviews with 12 Danish patients. Data
      analysis was performed according to the guidelines given in RLR. The essential
      meaning of losing a leg is a radical and existential upheaval, which restricts
      patients' lifestyle and irretrievably alters their lifeworld. Life after the
      operation is associated with despair, and a painful sense of loss, but also with
      the hope of regaining personal independence. The consequences of losing a leg
      gradually materialize as the patients realize how the loss of mobility limits
      their freedom. Patients experience the professional help as primarily directed
      towards physical care and rehabilitation. The findings show that the loss of a
      leg and, subsequently, the restricted mobility carry with them an existential
      dimension which refers to limitation of action space and loss of freedom
      experienced as an exclusion from life. Our findings demonstrate a need for
      complementary care and stress the importance of an increased awareness of the
      psychosocial and existential consequences of losing a limb. 

PMID- 24128664
TI  - Increased susceptibility to apoptosis in cultured fibroblasts from antipsychotic
      naive first-episode schizophrenia patients.
AB  - Altered apoptosis has been proposed as a potential mechanism involved in the
      abnormal neurodevelopment and neurodegenerative processes associated with
      schizophrenia. The aim of this study was to investigate in primary fibroblast
      cultures whether antipsychotic-naive patients with first-episode schizophrenia
      have greater apoptotic susceptibility than healthy controls. Cell growth, cell
      viability and various apoptotic hallmarks (caspase-3 activity, translocation of
      phosphatidylserine, chromatin condensation and gene expression of AKT1, BAX,
      BCL2, CASP3, GSK3B and P53) were measured in fibroblast cultures obtained from
      skin biopsies of patients (n = 11) and healthy controls (n = 8), both in basal
      conditions and after inducing apoptosis with staurosporine. Compared to controls,
      cultured fibroblasts from patients showed higher caspase-3 activity and lower
      BCL2 expression. When exposed to staurosporine, fibroblasts from patients also
      showed higher caspase-3 activity; a higher percentage of cells with translocated
      phosphatidylserine and condensed chromatin; and higher p53 expression compared to
      fibroblasts from controls. No differences in cell viability or cell growth were
      detected. These results strongly support the hypothesis that first-episode
      schizophrenia patients may have increased susceptibility to apoptosis, which may
      be involved in the onset and progression of the disease.

PMID- 24128662
TI  - Calpain-mediated degradation of MDMx/MDM4 contributes to HIV-induced neuronal
      damage.
AB  - Neuronal damage in HIV-associated Neurocognitive Disorders (HAND) has been linked
      to inflammation induced by soluble factors released by HIV-infected, and non
      infected, activated macrophages/microglia (HIV M/M) in the brain. It has been
      suggested that aberrant neuronal cell cycle activation determines cell fate in
      response to these toxic factors. We have previously shown increased expression of
      cell cycle proteins such as E2F1 and phosphorylated pRb in HAND midfrontal cortex
      in vivo and in primary neurons exposed to HIV M/M supernatants in vitro. In
      addition, we have previously shown that MDMx (also referred to as MDM4), a
      negative regulator of E2F1, was decreased in the brain in a primate model of HIV
      induced CNS neurodegeneration. Thus, we hypothesized that MDMx provides indirect
      neuroprotection from HIV-induced neurodegeneration in our in vitro model. In this
      report, we found significant reductions in MDMx protein levels in the mid-frontal
      cortex of patients with HAND. In addition, treatment of primary rat neuroglial
      cultures with HIV M/M led to NMDA receptor- and calpain-dependent degradation of
      MDMx and decreased neuronal survival, while overexpression of MDMx conferred
      partial protection from HIV M/M toxicity in vitro. Further, our results
      demonstrate that MDMx is a novel and direct calpain substrate. Finally, blocking
      MDMx activity led to neuronal death in vitro in the absence of toxic stimulus,
      which was reversed by calpain inhibition. Overall, our results indicate that MDMx
      plays a pro-survival role in neurons, and that strategies to stabilize and/or
      induce MDMx can provide neuroprotection in HAND and in other neurodegenerative
      diseases where calpain activation contributes to neuropathogenesis. 

PMID- 24128665
TI  - Family members' views on the benefits of harp music vigils for terminally-ill or
      dying loved ones.
AB  - OBJECTIVES: Music-thanatology is a palliative modality that uses harp and voice
      to provide bedside vigils, particularly for terminally ill or actively dying. We
      sought to determine the benefits of music vigils for terminally ill patients.
      METHODS: Survey of 55 family members, whose terminally ill loved one experienced
      a music vigil during hospitalization, regarding effects on the patient's
      breathing, relaxation, comfort, pain and ability to sleep. Written comments on
      negative and positive results of the vigils were coded using content analysis.
      RESULTS: Family members perceived that the vigils resulted in modest improvement
      in the patients' breathing, relaxation, comfort, and ability to sleep, with fewer
      positive effects on pain, and almost no negative effects. Open ended comments
      focused on the positive benefit in increasing calm, relaxation, comfort. Comments
      on the positive effects for the family were almost as common as comments on the
      positive results for the patient. SIGNIFICANCE OF RESULTS: The use of music
      vigils in palliative care should be investigated more extensively as our study
      supports that this intervention has benefits, almost no risk, minimal cost, and
      may improve patient-family experience of the dying process.

PMID- 24128663
TI  - Reprogramming fibroblasts to neural-precursor-like cells by structured
      overexpression of pallial patterning genes.
AB  - In this study, we assayed the capability of four genes implicated in embryonic
      specification of the cortico-cerebral field, Foxg1, Pax6, Emx2 and Lhx2, to
      reprogramme mouse embryonic fibroblasts towards neural identities. Lentivirus
      mediated, TetON-dependent overexpression of Pax6 and Foxg1 transgenes
      specifically activated the neural stem cell (NSC) reporter Sox1-EGFP in a
      substantial fraction of engineered cells. The efficiency of this process was
      enhanced up to ten times by simultaneous inactivation of Trp53 and co
      administration of a specific drug mix inhibiting HDACs, H3K27-HMTase and H3K4m2
      demethylase. Remarkably, a fraction of the reprogrammed population expressed
      other NSC markers and retained its new identity, even after switching off the
      reprogramming transgenes. When transferred into a pro-differentiative
      environment, Pax6/Foxg1-overexpressing cells activated the neuronal marker Tau
      EGFP. Frequency of Tau-EGFP positive cells was almost doubled upon delayed
      delivery of Emx2 and Lhx2 transgenes. A further improvement of the neuron-like
      cell output was achieved by inhibition of the BMP and TGFbeta pathways. Tau-EGFP
      positive cells were able to generate action potentials upon injection of
      depolarizing current pulses, further indicating their neuron-like phenotype. 

PMID- 24128666
TI  - Gentamicin in bone cement: A potentially more effective prophylactic measure of
      infectionin joint arthroplasty.
AB  - OBJECTIVES: The objective of this study is to determine an optimal antibiotic
      loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty
      (TJA). METHODS: We evaluated the antibacterial effects of polymethylmethacrylate
      (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem,
      piperacillin, gentamicin, and tobramycin against methicillin-sensitive
      Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA),
      coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas
      aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40
      g PMMA loaded with 1 g antibiotics were tested for elution characteristics,
      antibacterial activities, and compressive strength in vitro. RESULTS: The ALBC
      containing gentamicin provided a much longer duration of antibiotic release than
      those containing other antibiotic. Imipenem-loading on the cement had a
      significant adverse effect on the compressive strength of the ALBC, which made it
      insufficient for use in prosthesis fixation. All of the tested antibiotics
      maintained their antibacterial properties after being mixed with PMMA. The
      gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the
      test organisms and had the greatest duration of antibacterial activity against
      MSSA, CoNS, P. aeruginosa and E. coli. CONCLUSION: When considering the use of
      ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very
      effective choice. Cite this article: Bone Joint Res 2013;2:220-6.

PMID- 24128667
TI  - Dual therapy with etravirine plus raltegravir for virologically suppressed HIV
      infected patients: a pilot study.
AB  - BACKGROUND: Clinical use of protease inhibitors (PIs) and nucleoside reverse
      transcriptase inhibitors (NRTIs) may be hampered by toxicity, interactions or
      resistance issues. Simple and effective antiretroviral regimens avoiding both
      drug classes may be needed for selected patients. METHODS: This was a prospective
      cohort study. Virologically suppressed patients on PI or NRTI regimens, with
      problems of tolerability, safety concerns due to comorbidities or risk of drug
      interactions for both PIs and NRTIs, were given the opportunity to switch their
      regimen to etravirine plus raltegravir. Patients were required not to have prior
      virological failure to raltegravir and if there was prior non-nucleoside reverse
      transcriptase inhibitor (NNRTI) virological failure, only patients in whom
      efficacy of etravirine could be anticipated through the Stanford Drug Resistance
      Database were included. Follow-up was scheduled for at least 48 weeks, unless the
      patient was lost to follow-up or discontinued therapy. RESULTS: Twenty-five
      patients were included. Their median age was 54 years; they had a median of 16
      years on antiretroviral therapy and a median of nine previous regimens; 21 (84%)
      patients had previous virological failure; and 15 (60%) patients had a genotypic
      test that showed three or more NRTI mutations in 9 (36%), four or more PI
      mutations in 11 (44%) and at least one NNRTI mutation in 8 (32%) patients. At 48
      weeks efficacy was 84% (95% CI 65.3%-93.6%) by intent-to-treat analysis and 91.3%
      (95% CI 73.2%-97.6%) by per-protocol analysis. One (4%) patient died, two (8%)
      discontinued due to intolerance and one (4%) experienced virological failure. The
      CD4/CD8 ratio and plasma lipids improved. CONCLUSIONS: Dual therapy with
      etravirine plus raltegravir was well tolerated and maintained durable viral
      suppression in selected virologically suppressed patients for whom both PI and
      NRTI therapy was challenging.

PMID- 24128668
TI  - In vitro activity of cadazolid against clinically relevant Clostridium difficile
      isolates and in an in vitro gut model of C. difficile infection.
AB  - OBJECTIVES: We investigated the in vitro activity of cadazolid against 100
      Clostridium difficile isolates and its efficacy in a simulated human gut model of
      C. difficile infection (CDI). METHODS: MICs of cadazolid, metronidazole,
      vancomycin, moxifloxacin and linezolid were determined using agar incorporation
      for 100 C. difficile isolates, including 30 epidemic strains (ribotypes 027, 106
      and 001) with reduced metronidazole susceptibility, 2 linezolid-resistant
      isolates and 2 moxifloxacin-resistant isolates. We evaluated the efficacy of two
      cadazolid dosing regimens (250 versus 750 mg/L twice daily for 7 days) to treat
      simulated CDI. Microflora populations, C. difficile total viable counts and
      spores, cytotoxin titres, possible emergence of cadazolid, linezolid or quinolone
      resistance, and antimicrobial concentrations were monitored throughout. RESULTS:
      Cadazolid was active against all (including linezolid- and moxifloxacin
      resistant) C. difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The
      cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than
      those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively.
      Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and
      cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50-100
      fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut
      microflora was limited, with the exception of bifidobacteria; Bacteroides
      fragilis group and Lactobacillus spp. counts were unaffected. There was no
      evidence for selection of strains resistant to cadazolid, quinolones or
      linezolid. CONCLUSIONS: Cadazolid activity was greater than other tested
      antimicrobials against 100 C. difficile strains. Cadazolid effectively treated
      simulated CDI in a gut model, with limited impact on the enumerated gut
      microflora and no signs of recurrence or emergence of resistance within the
      experimental timeframe.

PMID- 24128669
TI  - Genotypic correlates of susceptibility to HIV-1 attachment inhibitor BMS-626529,
      the active agent of the prodrug BMS-663068.
AB  - OBJECTIVES: In an 8 day monotherapy study of subjects infected with HIV-1
      (subtype B) (NCT01009814), BMS-626529 (an attachment inhibitor that binds to HIV
      1 envelope glycoprotein gp120), administered as the prodrug BMS-663068, produced
      substantial declines in plasma HIV-1 RNA. However, large variability in
      susceptibility to BMS-626529 was noted and virus with low susceptibility was less
      likely to be suppressed by BMS-663068 administration. The current analysis sought
      to investigate the genotypic correlates of susceptibility to BMS-626529. METHODS:
      In vitro selection experiments, evaluation of clinical samples of subtype B from
      the monotherapy study and evaluation of intrinsically resistant subtype AE
      viruses were conducted. Reverse genetics was used to identify key substitutions
      in envelope clones responsible for reduced susceptibility. RESULTS: An M426L or
      S375M change were the major substitutions associated with reductions in
      susceptibility to BMS-626529 in baseline samples of subtype B viruses from the
      monotherapy study, with M434I and M475I contributing to a lesser extent. Class
      resistance in subtype AE viruses was mapped to 375H and 475I substitutions, found
      in the vast majority of these viruses. Analysis of multiple envelope clones from
      infected subjects showed higher intrasubject variability in susceptibility to BMS
      626529 compared with other classes of entry inhibitors. CONCLUSIONS: These data
      define key genotypic substitutions in HIV-1 gp120 that could confer phenotypic
      resistance to BMS-626529.

PMID- 24128670
TI  - Correlates of body depilation: an exploratory study into the health implications
      of body hair reduction and removal among college-aged men.
AB  - Recent studies suggest that body hair may be of increasing importance in men's
      overall body image. Body depilation is a relatively new area of clinical and
      research inquiry among men with much of the documented evidence of the phenomenon
      split between mass media accounts and descriptive scientific investigations. This
      study was undertaken to further our understanding of this behavior by examining
      the relationship between depilation and other dimensions of body image in a
      nonclinical sample. A total of 364 men completed measures assessing self-reported
      hair growth, body depilation, drive for muscularity, gender role conflict, body
      dysmorphia, and social comparison. The correlates of body depilation included a
      drive for muscularity, gender role conflict, and physical appearance social
      comparison. Significant differences were identified among men who depilate,
      compared with those who do not, on measures of social comparison and a drive for
      muscularity. These findings lend support for the idea that body hair, and its
      reduction or removal, is a key aspect of men's body image that translates into
      some challenges in assessment and prevention among health care practitioners.

PMID- 24128671
TI  - Commercial sex and condom use among involuntary bachelors: an exploratory survey
      in rural China.
AB  - In the present context of the Chinese male marriage squeeze, commercial sex is
      becoming an important way for bachelors to meet their sexual needs. Using data
      from a survey conducted in a rural district of Anhui province, China, this study
      analyzes commercial sex experiences and condom use among involuntary bachelors
      and compares usage in this population to that observed in married men in the same
      age groups. Our findings indicate that, for both first and most recent sexual
      intercourse, the prevalence of commercial sex among unmarried men is
      significantly higher than that reported among married men; indeed, marital status
      was the only variable that was consistently related to rates of commercial sex
      for both first and most recent sexual intercourse. The vast majority of sexual
      intercourse was still unprotected, and the rate of condom use was not only lower
      among unmarried men than among married men, but was also significantly related to
      knowledge of sexually transmitted diseases, as well as age, education, and
      income. Because of their lower condom use, unmarried men face much higher risks
      of contracting and spreading sexually transmitted diseases than married men do.
      This situation poses a severe threat to public health.

PMID- 24128672
TI  - Autophagy protects kidney proximal tubule epithelial cells from mitochondrial
      metabolic stress.
AB  - Chronic metabolic stress is related to diseases, whereas autophagy supplies
      nutrients by recycling the degradative products. Cyclosporin A (CsA), a
      frequently used immunosuppressant, induces metabolic stress via effects on
      mitochondrial respiration, and thereby, its chronic usage is often limited. Here
      we show that autophagy plays a protective role against CsA-induced metabolic
      stress in kidney proximal tubule epithelial cells. Autophagy deficiency leads to
      decreased mitochondrial membrane potential, which coincides with metabolic
      abnormalities as characterized by decreased levels of amino acids, increased
      tricarboxylic acid (TCA) ratio (the levels of intermediates of the latter part of
      the TCA cycle, over levels of intermediates in the earlier part), and decreased
      products of oxidative phosphorylation (ATP). In addition to the altered profile
      of amino acids, CsA decreased the hyperpolarization of mitochondria with the
      disturbance of mitochondrial energy metabolism in autophagy-competent cells,
      i.e., increased TCA ratio and worsening of the NAD(+)/NADH ratio, coupled with
      decreased energy status, which suggests that adaptation to CsA employs autophagy
      to supply electron donors from amino acids via intermediates of the latter part
      of the TCA cycle. The TCA ratio of autophagy-deficient cells was further worsened
      with decreased levels of amino acids in response to CsA, and, as a result, the
      deficiency of autophagy failed to adapt to the CsA-induced metabolic stress.
      Deterioration of the TCA ratio further worsened energy status. The CsA-induced
      metabolic stress also activated regulatory genes of metabolism and apoptotic
      signals, whose expressions were accelerated in autophagy-deficient cells. These
      data provide new perspectives on autophagy in conditions of chronic metabolic
      stress in disease. 

PMID- 24128673
TI  - Targeted cancer therapy--are the days of systemic chemotherapy numbered?
AB  - Targeted therapy or molecular targeted therapy has been defined as a type of
      treatment that blocks the growth of cancer cells by interfering with specific
      cell molecules required for carcinogenesis and tumor growth, rather than by
      simply interfering with all rapidly dividing cells as with traditional
      chemotherapy. There is a growing number of FDA approved monoclonal antibodies and
      small molecules targeting specific types of cancer suggestive of the growing
      relevance of this therapeutic approach. Targeted cancer therapies, also referred
      to as "Personalized Medicine", are being studied for use alone, in combination
      with other targeted therapies, and in combination with chemotherapy. The
      objective of personalized medicine is the identification of patients that would
      benefit from a specific treatment based on the expression of molecular markers.
      Examples of this approach include bevacizumab and olaparib, which have been
      designated as promising targeted therapies for ovarian cancer. Combinations of
      trastuzumab with pertuzumab, or T-DM1 and mTOR inhibitors added to an aromatase
      inhibitor are new therapeutic strategies for breast cancer. Although this
      approach has been seen as a major step in the expansion of personalized medicine,
      it has substantial limitations including its high cost and the presence of
      serious adverse effects. The Cancer Genome Atlas is a useful resource to identify
      novel and more effective targets, which may help to overcome the present
      limitations. In this review we will discuss the clinical outcome of some of these
      new therapies with a focus on ovarian and breast cancer. We will also discuss
      novel concepts in targeted therapy, the target of cancer stem cells. 

PMID- 24128674
TI  - The health benefits of network growth: new evidence from a national survey of
      older adults.
AB  - Scholars who study how social networks affect older adults' health are often
      concerned with the prospect of declining social connectedness in late life. This
      paper shifts the focus to older adults' tendencies to cultivate new social ties.
      This process of network growth can improve access to social resources, boost self
      esteem, reduce loneliness, and increase physical activity. We therefore examine
      the link between tie cultivation and health using new longitudinal data from the
      National Social Life, Health, and Aging Project (NSHAP), which recorded changes
      in older adults' confidant network rosters over a period of about five years.
      Most respondents (81.8%) added at least one new network member during the study
      period, and most (59.4%) cultivated multiple new confidant relationships.
      Longitudinal analyses suggest that the addition of new confidants is associated
      with improvements in functional, self-rated, and psychological health, net of
      baseline connectedness as well as any network losses that occurred during the
      same period. Network losses were associated with physical but not psychological
      well-being. These findings underscore the importance of distinguishing between
      concurrent processes that underlie social network change in later life, and
      highlight the need for additional research on the mechanisms by which network
      change may improve health. 

PMID- 24128675
TI  - Abnormal gephyrin immunoreactivity associated with Alzheimer disease pathologic
      changes.
AB  - Many neurodegenerative disorders involve the abnormal accumulation of proteins.
      In addition to the pathologic hallmarks of neurofibrillary tangles and beta
      amyloid plaques in Alzheimer disease (AD), here we show that abnormal
      accumulations of gephyrin, an inhibitory receptor-anchoring protein, are highly
      correlated with the neuropathologic diagnosis of AD in 17 AD versus 14 control
      cases. Furthermore, gephyrin accumulations were specific for AD and not seen in
      normal controls or other neurodegenerative diseases including Parkinson disease,
      corticobasal degeneration, and frontotemporal degeneration. Gephyrin
      accumulations in AD overlapped with beta-amyloid plaques and, more rarely,
      neurofibrillary tangles. Biochemical and proteomic studies of AD and control
      brain samples suggested alterations in gephyrin solubility and reveal elevated
      levels of gephyrin lower-molecular-weight species in the AD insoluble fraction.
      Because gephyrin is involved in synaptic organization and synaptic dysfunction is
      an early event in AD, these findings point to its possible role in the
      pathogenesis of AD. 

PMID- 24128677
TI  - Neurotrophins in mesial temporal lobe epilepsy with and without psychiatric
      comorbidities.
AB  - Despite the strong association between epilepsy and psychiatric comorbidities,
      data on clinicopathologic correlations are scant. We previously reported
      differential mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (MTLE)
      patients with psychosis (MTLE + P) and major depression (MTLE + D). Because
      neurotrophins (NTs) can promote MFS, here, we investigated MFS, neuronal density
      and immunoreactivity for the NT nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in hippocampi of 14 MTLE
      patients without a psychiatric history, 13 MTLE + D, 13 MTLE + P, and 10 control
      necropsies. Mossy fiber sprouting correlated with granular layer NGF
      immunoreactivity and seizure frequency. Patients with secondarily generalized
      seizures exhibited less NGF immunoreactivity versus patients with complex partial
      seizures. There was greater NT immunoreactivity in MTLE versus control groups but
      lesser NT immunoreactivity in MTLE + P versus MTLE patients; these findings
      correlated with neuropsychologic scores. Patients with MTLE + D taking fluoxetine
      showed greater BDNF immunoreactivity than those not taking fluoxetine; MTLE + P
      patients taking haloperidol had decreased neuronal density and immunoreactivity
      for NGF and BDNF in specific subfields versus those not taking haloperidol. There
      were no differences in NT3 immunoreactivity among the groups. These findings
      support a close association between MFS and NT expression in the hippocampi of
      MTLE patients and suggest that distinct structural and neurochemical milieu may
      contribute to the genesis or maintenance of psychiatric comorbidities in MTLE. 

PMID- 24128676
TI  - A rapid gene delivery-based mouse model for early-stage Alzheimer disease-type
      tauopathy.
AB  - The perforant pathway projection from the entorhinal cortex (EC) to the
      hippocampal dentate gyrus is critically important for long-term memory and
      develops tau and amyloid pathologies and progressive degeneration starting in the
      early stages of Alzheimer disease (AD). However, perforant pathway function has
      not been assessed in experimental models of AD, and a therapeutic agent that
      protects its structure and function has not yet been identified. Therefore, we
      developed a new adeno-associated virus-based mouse model for perforant pathway
      tauopathy. Microinjection into the lateral EC of vectors designed to express
      either human tau bearing a pathogenic P301L mutation or enhanced green
      fluorescent protein as a control selectively drove transgene expression in
      lateral EC layer II perikarya and along the entire rostrocaudal extent of the
      lateral perforant pathway afferents and dentate terminal field. After human tau
      expression, hyperphosphorylated tau accumulated only within EC layer II
      perikarya, thereby modeling Braak stage I of transentorhinal AD tauopathy.
      Expression of pathologic human tau but not enhanced green fluorescent protein led
      to specific dose-dependent apoptotic death of perforant pathway neurons and loss
      of synapses in as little as 2 weeks. This novel adeno-associated virus-based
      method elicits rapid tauopathy and tau-mediated neurodegeneration localized to
      the mouse perforant pathway and represents a new experimental approach for
      studying tau-driven pathogenic processes and tau-based treatment strategies in a
      highly vulnerable neural circuit. 

PMID- 24128678
TI  - Altered expression of DJ-1 and PINK1 in sporadic ALS and in the SOD1(G93A) ALS
      mouse model.
AB  - Mitochondrial dysfunction is an important mechanism in the pathogenesis of
      neurodegenerative diseases such as Parkinson disease and amyotrophic lateral
      sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important
      proteins for the maintenance of mitochondrial function and protection against
      cell death. Mutations in the genes coding for these proteins cause familial forms
      of Parkinson disease. Recent studies have postulated that changes in the
      expression of both proteins are also involved in pathologic mechanisms in ALS
      mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1
      in postmortem brain and spinal cord tissue and muscle biopsy samples from ALS
      patients and controls and in brain, spinal cord, and gastrocnemius muscle of
      SOD1(G93A) ALS mice at different disease stages. We found significant decreases
      of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with
      the significant decrease of PINK1 mRNA levels in human ALS muscle tissue,
      statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced
      immunostaining for PINK1 in human ALS muscle, the results suggest potential
      pathophysiologic roles for these proteins in both mutant SOD1 transgenic mice and
      in sporadic ALS(G93A).

PMID- 24128679
TI  - Pathogenesis of autosomal dominant hereditary spastic paraplegia (SPG6) revealed
      by a rat model.
AB  - Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity
      and weakness in the lower extremities that result from length-dependent central
      to peripheral axonal degeneration. Mutations in the non-imprinted Prader
      Willi/Angelman syndrome locus 1 (NIPA1) transmembrane protein cause an autosomal
      dominant form of HSP (SPG6). Here, we report that transgenic (Tg) rats expressing
      a human NIPA1/SPG6 mutation in neurons (Thy1.2-hNIPA1) show marked early onset
      behavioral and electrophysiologic abnormalities. Detailed morphologic analyses
      reveal unique histopathologic findings, including the accumulation of
      tubulovesicular organelles with endosomal features that start at axonal and
      dendritic terminals, followed by multifocal vacuolar degeneration in both the CNS
      and peripheral nerves. In addition, the NIPA1 mutation in the spinal cord from
      older Tg rats results in an increase in bone morphogenetic protein type II
      receptor expression, suggesting that its degradation is impaired. This Thy1.2
      hNIPA1 Tg rat model may serve as a valuable tool for understanding endosomal
      trafficking in the pathogenesis of a subgroup of HSP with an abnormal interaction
      with bone morphogenetic protein type II receptor, as well as for developing
      potential therapeutic strategies for diseases with axonal degeneration and
      similar pathogenetic mechanisms. 

PMID- 24128680
TI  - Natalizumab-associated progressive multifocal leukoencephalopathy in a patient
      with multiple sclerosis: a postmortem study.
AB  - Natalizumab, a monoclonal antibody directed against alpha4 integrins, has, to
      date, been associated with 399 cases of progressive multifocal
      leukoencephalopathy (PML) worldwide in patients receiving treatment for multiple
      sclerosis (MS). Because of the limited number of histologic studies, the possible
      interplay between MS and PML lesions has not been investigated. We report the
      clinical, radiologic, and histologic findings of an MS patient who developed PML
      after 32 months of natalizumab monotherapy. After withdrawal of natalizumab, she
      received plasma exchange, mefloquine, and mirtazapine but died soon thereafter.
      Postmortem examination was restricted to examination of the brain and spinal
      cord. Extensive PML lesions, characterized by the presence of JC virus DNA were
      found in the cerebral white matter and neocortex. Sharply demarcated areas of
      active PML lesions contained prominent inflammatory infiltrates composed of
      approximately equal numbers of CD4-positive and CD8-positive T cells, consistent
      with an immune reconstitution inflammatory syndrome. Conversely, all MS lesions
      identified were hypocellular, long-standing inactive plaques characterized by
      myelin loss, relative axonal preservation, and gliosis and, importantly, were
      devoid of JC virus DNA and active inflammation. Chronic inactive MS lesions were
      separate and distinct from nearby PML lesions. This case demonstrates the
      coexistence and apparent lack of interplay between chronic inactive MS and PML
      lesions, and that immune reconstitution inflammatory syndrome seems to affect the
      shape and appearance of PML but not MS lesions. 

PMID- 24128682
TI  - Upregulation of adenosine kinase in Rasmussen encephalitis.
AB  - Rasmussen encephalitis (RE) is a rare neurologic disorder of childhood
      characterized by unihemispheric inflammation, progressive neurologic deficits,
      and intractable focal epilepsy. The pathogenesis of RE is still enigmatic.
      Adenosine is a key endogenous signaling molecule with anticonvulsive and anti
      inflammatory effects, and our previous work demonstrated that dysfunction of the
      adenosine kinase (ADK)-adenosine system and astrogliosis are the hallmarks of
      epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE are
      related to changes in ADK expression and that those changes might be associated
      with the development of epilepsy in RE patients. Immunohistochemistry was used to
      examine the expression of ADK and glial fibrillary acidic protein in surgically
      resected human epileptic cortical specimens from RE patients (n = 12) and
      compared with control cortical tissues (n = 6). Adenosine kinase expression using
      Western blot and enzymatic activity for ADK were assessed in RE versus control
      samples. Focal astrogliosis and marked expression of ADK were observed in the
      lesions of RE. Significantly greater ADK expression in RE versus controls was
      demonstrated by Western blot, and greater enzymatic activity for ADK was
      demonstrated using an enzyme-coupled bioluminescent assay. These results suggest
      that upregulation of ADK is a common pathologic hallmark of RE and that ADK might
      be a target in the treatment of epilepsy associated with RE. 

PMID- 24128683
TI  - Adult-onset leukodystrophy: review of 3 clinicopathologic phenotypes and a
      proposed classification.
AB  - Adult-onset leukodystrophies are clinically and pathologically heterogeneous
      diseases, and the overlapping morphologic features among these disorders can lead
      to confusion in pathologic classification. We report 3 recent autopsy cases that
      illustrate the clinicopathologic distinction between the 3 entities. The first,
      autosomal dominant leukodystrophy, is characterized clinically by early autonomic
      dysfunction and genetically by LMNB1 (lamin B1 gene) duplication. Recently,
      another clinical subtype emerged without the early autonomic dysfunction but with
      a similar genetic abnormality documented in 1 family. We reviewed the reported
      autopsy cases and show that both clinical subtypes share distinctive pathologic
      features. Other forms of adult-onset leukodystrophy can be classified based on
      the histologic evidence of the primary pathologic processes. A case of axonopathy
      with secondary demyelination serves as a prototype for adult-onset
      leukoencephalopathy/leukodystrophy with axonal spheroids; the genetic mutation of
      CSF1R (colony stimulating factor 1R) was recently discovered in patients with
      this disorder. A case of a primary demyelinating disease with no other
      distinctive pathologic features is designated as orthochromatic leukodystrophy.
      Pigmented glia can be present in both of the latter two categories and should not
      be used as a differentiating diagnostic feature. Based on the observations of our
      cases and literature review, we propose an algorithm for a practical diagnostic
      approach to adult-onset leukodystrophies. 

PMID- 24128681
TI  - Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles
      in axonopathy and neuron degeneration.
AB  - Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging
      roles in neurologic diseases. To illuminate their contributions to the
      pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic
      changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7,
      KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA
      expression levels in experimental murine SCI, and assessed the impact of
      recombinant forms of each enzyme toward murine cortical neurons in vitro.
      Temporally and spatially distinct changes in KLK expression were observed with
      partially overlapping patterns between human and murine SCI, including peak
      elevations (or reductions) during the acute and subacute periods. Kallikrein 9
      showed the most marked changes and remained chronically elevated. Importantly, a
      subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary
      neurons in vitro. Kallikrein immunoreactivity was also observed in association
      with swollen axons and retraction bulbs in the human SCI cases examined.
      Together, these findings demonstrate that elevated levels of a significant subset
      of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS
      trauma and disease and, therefore, represent new potential targets for the
      development of neuroprotective strategies. 

PMID- 24128684
TI  - Is schizophrenia a dopamine supersensitivity psychotic reaction?
AB  - Adolf Meyer (1866-1950) did not see schizophrenia as a discrete disorder with a
      specific etiology but, rather, as a reaction to a wide variety of biopsychosocial
      factors. He may have been right. Today, we have evidence that gene mutations,
      brain injury, drug use (cocaine, amphetamine, marijuana, phencyclidine, and
      steroids), prenatal infection and malnutrition, social isolation and
      marginalization, can all result in the signs and symptoms of schizophrenia. This
      clinical picture is generally associated with supersensitivity to dopamine, and
      activates dopamine neurotransmission that is usually alleviated or blocked by
      drugs that block dopamine D2 receptors. While the dopamine neural pathway may be
      a final common route to many of the clinical symptoms, the components of this
      pathway, such as dopamine release and number of D2 receptors, are approximately
      normal in schizophrenia patients who are in remission. Postmortem findings,
      however, reveal more dimers of D1D2 and D2D2 receptors in both human
      schizophrenia brains and in animal models of schizophrenia. Another finding in
      animal models is an elevation of high-affinity state D2High receptors, but no
      radioactive ligand is yet available to selectively label D2High receptors in
      humans. It is suggested that synaptic dopamine supersensitivity in schizophrenia
      is an attempt at compensation for the original damage by heightening dopamine
      neurotransmission pathways (preparing the organism for fight or flight). The
      dopamine overactivity is experienced subjectively as overstimulation, which
      accounts for some of the clinical symptoms, with attempts at dampening down the
      stimulation leading to still other symptoms. Reaction and counter-reaction may
      explain the symptoms of schizophrenia. 

PMID- 24128685
TI  - Brief maternal separation affects brain alpha1-adrenoceptors and apoptotic
      signaling in adult mice.
AB  - Exposure to adversity during early life is a risk factor for the development of
      different mood and psychiatric disorders, including depressive-like behaviors.
      Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated
      from mothers and placed in a testing environment containing a layer of odorless
      clean bedding (CB). We assessed in adult animals the impact of this early
      experience on binding sites and mRNA expression of alpha1-adrenergic receptor
      subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members
      of the Bcl-2 family proteins in different brain regions involved in processing of
      olfactory information and rewarding stimuli. We found that repeated exposure to
      CB experience produced anhedonic-like behavior in terms of reduced saccharin
      intake and alpha1-adrenoceptor downregulation in piriform and somatosensory
      cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a
      selective decrease of alpha1B-adrenoceptor binding sites in the cingulate cortex
      and hippocampus and an increase of hippocampal alpha1A and alpha1B receptor, but
      not of alpha1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease
      of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the
      prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family
      proteins was found at the hippocampal level. Together, these data provide
      evidence that the early exposure to CB experience produced enduring
      downregulation of alpha1-adrenoceptors in the prefrontal-limbic forebrain/limbic
      midbrain network, which plays a key role in the processing of olfactory
      information and reaction to rewarding stimuli. Finally, these data show that CB
      experience can "prime" the hippocampal circuitry and promote the expression of
      antiapoptotic factors that can confer potential neuroprotection to subsequent
      adversity. 

PMID- 24128686
TI  - Benzimidazole-resistant gastrointestinal nematodes in indigenous Chiapas and
      Pelibuey sheep breeds from Chiapas, Mexico.
AB  - Because of the natural adaptation of Mexican sheep, the aim of the present study
      was to identify the presence or absence of gastrointestinal parasitic nematodes
      (GIN) resistant to benzimidazole (BZ) in both Chiapas and Pelibuey sheep breeds
      on local farms. Both male and female GIN-infected grazing sheep of the two breeds
      were selected. Sheep faecal samples were collected to obtain infective larvae
      (L3). This evolving stage of the parasite was used for taxonomic identification
      of the genus, based on its morphological characteristics. BZ anthelmintic
      resistance was evaluated using a nematode-compound in vitro interaction bioassay
      and the allele-specific polymerase chain reaction technique to detect mutations
      of residues 198 and 200 on isotype 1 of the beta-tubulin gene. Three BZ-based
      compounds (febendazole (FBZ), tiabendazole (TBZ) and albendazole (ABZ)) at
      concentrations of 1, 0.5, 0.25, 0.125, 0.062 and 0.03 mg/ml were used to estimate
      the anthelmintic efficacy and lethal dose (LD50, LD90 and LD99) of the drugs. Two
      parasitic nematodes, Haemonchus and Teladorsagia, were identified in both
      isolates. Also, the proportions of anthelmintic resistance identified in GIN of
      the two sheep breeds were 68% in isolates from the Chiapas breed and 71.8% in the
      Pelibuey breed. The specific lethal activity obtained with FBZ was higher than
      90%. However, TBZ and ABZ showed a lethal activity lower than 50%. High
      variability in the discriminating dose values was found among the BZ drugs. For
      example, FBZ LD ranged from 0.01 to 1.20 mg/ml; on the other hand, TBZ and ABZ
      required a dose ranging from 0.178 to 759 mg/ml. In addition, amino acid changes
      of Phe (TTC) to Tyr (TAC) at codon 200 of the beta-tubulin gene, showing
      resistance to BZ, and no changes at codon 198 Glu (GAA) to Ala (GCA) were
      observed for both isolates. These results confirmed the presence of a genetic
      mutation associated with BZ in both Chiapas and Pelibuey nematode isolates. 

PMID- 24128687
TI  - Experimental and observational studies of seasonal interactions between
      overlapping life history stages in a migratory bird.
AB  - Prior to reproduction, migratory animals are at the juxtaposition of three life
      history stages in which they must finish the non-breeding stage, initiate and
      complete migration, and prepare for the onset of breeding. However, how these
      stages interact with one another is not fully understood. We provide evidence
      that, for migratory birds that begin breeding development prior to departure from
      non-breeding sites, the level of breeding preparation can drive migration
      phenology, a critical behavioral determinant of reproductive success.
      Specifically, male American redstart (Setophaga ruticilla) plasma androgen
      levels, which increase in males during the period leading into migration, were
      positively correlated with energetic condition. We empirically tested the
      hypothesis that elevated androgen simultaneously supports migratory and breeding
      preparation in a hormone manipulation field experiment. Males with testosterone
      implants showed advanced preparation for migration and breeding, and ultimately
      departed on migration earlier than controls. It is assumed that early departure
      leads to early arrival at breeding areas, which increases breeding success.
      Collectively, our observational and experimental results demonstrate how
      overlapping life history stages can interact to influence important components of
      an individual's fitness. This highlights the critical need for understanding
      population processes across the full life cycle of an organism to better
      understand the ecological and evolutionary origins of complex life history
      events.

PMID- 24128690
TI  - What basic number processing measures in kindergarten explain unique variability
      in first-grade arithmetic proficiency?
AB  - Relations between children's mathematics achievement and their basic number
      processing skills have been reported in both cross-sectional and longitudinal
      studies. Yet, some key questions are currently unresolved, including which
      kindergarten skills uniquely predict children's arithmetic fluency during the
      first year of formal schooling and the degree to which predictors are contingent
      on children's level of arithmetic proficiency. The current study assessed
      kindergarteners' non-symbolic and symbolic number processing efficiency. In
      addition, the contribution of children's underlying magnitude representations to
      differences in arithmetic achievement was assessed. Subsequently, in January of
      Grade 1, their arithmetic proficiency was assessed. Hierarchical regression
      analysis revealed that children's efficiency to compare digits, count, and
      estimate numerosities uniquely predicted arithmetic differences above and beyond
      the non-numerical factors included. Moreover, quantile regression analysis
      indicated that symbolic number processing efficiency was consistently a
      significant predictor of arithmetic achievement scores regardless of children's
      level of arithmetic proficiency, whereas their non-symbolic number processing
      efficiency was not. Finally, none of the task-specific effects indexing
      children's representational precision was significantly associated with
      arithmetic fluency. The implications of the results are 2-fold. First, the
      findings indicate that children's efficiency to process symbols is important for
      the development of their arithmetic fluency in Grade 1 above and beyond the
      influence of non-numerical factors. Second, the impact of children's non-symbolic
      number processing skills does not depend on their arithmetic achievement level
      given that they are selected from a nonclinical population. 

PMID- 24128689
TI  - Snapshot of an acute palliative care unit in a tertiary cancer hospital.
AB  - Most palliative care (PC) programs in the United States provide consultation
      services that assist the primary medical team with issues ranging from
      controlling patients' symptoms to initiating end-of-life discussions. This
      approach may be sufficient to address many patients' needs. However, for certain
      patients with complex medical and psychosocial issues, a better alternative is a
      more streamlined approach that can be provided in an acute palliative care unit
      (APCU), where the PC staff assumes the role of the primary team. An APCU is a
      specialized unit that delivers highly sophisticated care with professionals from
      various disciplines working together to improve the quality of life of patients
      and their families. However, descriptions of the process of delivering PC in the
      APCU are limited. In this special report, we portray a single day with a series
      of patients whose care was managed at our APCU to illustrate the unique
      components of an APCU that allow holistic care for patients with multiple complex
      medical and psychosocial issues. 

PMID- 24128688
TI  - LDL receptor-related protein-1: a regulator of inflammation in atherosclerosis,
      cancer, and injury to the nervous system.
AB  - Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytic
      receptor for numerous proteins that are both structurally and functionally
      diverse. In some cell types, LRP1-mediated endocytosis is coupled to activation
      of cell signaling. LRP1 also regulates the composition of the plasma membrane and
      may, thereby, indirectly regulate the activity of other cell-signaling receptors.
      Given the scope of LRP1 ligands and its multifunctional nature, it is not
      surprising that numerous biological activities have been attributed to this
      receptor. LRP1 gene deletion is embryonic-lethal in mice. However, elegant
      studies using Cre-LoxP recombination have helped elucidate the function of LRP1
      in mature normal and pathological tissues. One major theme that has emerged is
      the role of LRP1 as a regulator of inflammation. In this review, we will describe
      evidence for LRP1 as a regulator of inflammation in atherosclerosis, cancer, and
      injury to the nervous system. 

PMID- 24128691
TI  - Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral
      muscular dystrophy 2.
AB  - FSHD2 is a rare form of facioscapulohumeral muscular dystrophy (FSHD)
      characterized by the absence of a contraction in the D4Z4 macrosatellite repeat
      region on chromosome 4q35 that is the hallmark of FSHD1. However, hypomethylation
      of this region is common to both subtypes. Recently, mutations in SMCHD1 combined
      with a permissive 4q35 allele were reported to cause FSHD2. We identified a novel
      p.Lys275del SMCHD1 mutation in a family affected with FSHD2 using whole-exome
      sequencing and linkage analysis. This mutation alters a highly conserved amino
      acid in the ATPase domain of SMCHD1. Subject III-11 is a male who developed
      asymmetrical muscle weakness characteristic of FSHD at 13 years. Physical
      examination revealed marked bilateral atrophy at biceps brachii, bilateral
      scapular winging, some asymmetrical weakness at tibialis anterior and peroneal
      muscles, and mild lower facial weakness. Biopsy of biceps brachii in subject II
      5, the father of III-11, demonstrated lobulated fibers and dystrophic changes.
      Endomysial and perivascular inflammation was found, which has been reported in
      FSHD1 but not FSHD2. Given the previous report of SMCHD1 mutations in FSHD2 and
      the clinical presentations consistent with the FSHD phenotype, we conclude that
      the SMCHD1 mutation is the likely cause of the disease in this family.

PMID- 24128692
TI  - Expression and purification of a novel therapeutic single-chain variable fragment
      antibody against BNP from inclusion bodies of Escherichia coli.
AB  - Abnormal brain natriuretic peptide (BNP) secretion is regarded as the dominating
      mechanism of cerebral salt wasting syndrome (CSW), which results from a renal
      loss of sodium and water during intracranial disease leading to hyponatremia.
      Scale preparation of therapeutic single-chain variable fragment (scFv) that can
      neutralize elevated circulating BNP may have potential value for clinical use. In
      this report, we used a recently isolated humanized anti-BNP scFv fragment (3C1)
      as model antibody (Ab) to evaluate the potential of scale production of this
      therapeutic protein. The truncated gene encoding for scFv fragment cloned in
      pET22b (+) was mainly overexpressed as inclusion bodies in Escherichia coli (E.
      coli) Rosetta (DE3) pLysS cells. The insoluble fragment was solubilized and
      purified by Ni-NTA agarose resin under denaturation conditions, and recovered via
      an effective refolding buffer containing 50 mM Tris-HCl, pH 8.0, 0.15 M NaCl, 1
      mM EDTA, 0.5 M arginine, 2 mM GSH, 1 mM GSSG, and 5% glycerol. The refolded scFv
      fragment was concentrated by PEG20000, and dialyzed in PBS (containing 5%
      glycerol, pH 7.4). The final yield was approximately 10.2 mg active scFv fragment
      per liter of culture (3.4 g wet weight cells). The scFv fragment was more than
      95% pure assessed by SDS-PAGE assay. Recombinant scFv fragment with His tag
      displayed its immunoreactivity with anti-His tag Ab by western blotting. ELISA
      showed the scFv fragment specifically bound to BNP, and it displayed similar
      activity as the traditional anti-BNP monoclonal Ab (mAb). Thus, the current
      strategy allows convenient small-scale production of this therapeutic protein.

PMID- 24128693
TI  - Biochemical study of the extracellular aspartyl protease Eap1 from the
      phytopathogen fungus Sporisorium reilianum.
AB  - In this work, the extracellular protease Eap1 from Sporisorium reilianum was
      characterized in solid and liquid cultures using different culture media. The
      results showed that Eap1 was produced in all media and under all culture
      conditions, with the most activity in solid culture at an acidic pH of 3-5.
      Following purification, the 41 kDa protease demonstrated aspartyl protease
      activity. The enzyme was stable at a wide range of temperatures and pH values,
      but 45 degrees C and pH 3 were optimal. The K(m) and V(max( values obtained were
      0.69 mg/mL and 0.66 MUmol/min, respectively, with albumin as the substrate. Eap1
      degraded hemoglobin as well as proteins obtained from corn germ, roots, stems and
      slides at pH 3 and also had milk-clotting activity. Sequencing analysis showed
      that this protein has 100% similarity to the peptide sequence theoretically
      obtained from the sr11394 gene, which encodes an aspartyl protease secreted by S.
      reilianum.

PMID- 24128694
TI  - Impact of an intragenic retrotransposon on the structural integrity and evolution
      of a major isoprenoid biosynthesis pathway gene in Hevea brasiliensis.
AB  - Isoprenoids belong to a large family of structurally and functionally different
      natural compounds found universally from prokaryotes to higher animals and
      plants. In Hevea brasiliensis, the commercially important cis-polyisoprene
      (rubber) is synthesised as part of its defence mechanism in addition to other
      common isoprenoids like phytosterols, growth hormones etc. Farnesyl diphosphate
      synthase (FDPS) is a key enzyme in this process which catalyses the conversion of
      isoprene units into polyisoprene. Although prior sequence information is
      available, the structural variants of the FDPS gene presently existing in Hevea
      population are largely unknown. Since gene structure has a major role in gene
      regulation, extensive sequence analysis of this gene from different genotypes was
      carried out to identify the prevailing structural variants. We identified several
      SNPs and large indels which were associated with a partial transposable element
      (TE). Modification of key regulatory motifs and splice sites induced by the
      retroelement was also identified in the first intron. Screening of popular rubber
      clones, wild germplasm accessions and Hevea species revealed that the
      retroelement is responsible for the generation of new alleles with varying
      degrees of sequence homology. Segregation analysis of a progeny population
      confirmed that the alleles are not paralogs and are inherited in a Mendelian
      mode. Our findings suggest that the first intron of the FDPS gene has been
      subjected to various chromosomal rearrangements due to the interaction of a
      retrotransposon, resulting in novel alleles which may substantially contribute
      towards the evolution of this major gene in rubber. Moreover, the results
      indicate the possible existence of a retrotransposon-mediated epigenetic gene
      regulatory mechanism in Hevea. 

PMID- 24128695
TI  - Intracerebral hemorrhage in young patients from a tertiary neurology center in
      North India.
AB  - OBJECTIVE: There is paucity of information on the etiology and predictors of
      outcome of intracerebral hemorrhage (ICH) in young patients which may have
      regional and ethnic differences. In this study, we report the etiology and
      predictors of outcome of ICH in young patients from North India. METHODS: 404
      young patients with ICH (16-50 years) were retrospectively reviewed who were
      admitted in neurology service of a tertiary care teaching hospital in North
      India. The data were retrieved from the computerized hospital information
      service. The information about the demography, risk factors, clinical status,
      laboratory findings, CT/MRI features and angiography (CT, MRI or digital
      substraction) were noted. The etiology of ICH was ascertained based on clinical,
      laboratory and radiological findings. Outcome at 1 month was assessed using
      Glasgow Outcome Scale (GOS). RESULTS: The mean age of the patients was 41.6 years
      and 23.8% were females. Hypertension (57.2%), hypocholesterolemia (33.7%),
      alcohol (15.8%) and anticoagulant (3.5%) were the important risk factors. The
      etiology of ICH was hypertension in 320 (79.2%), vascular malformation in 17
      (4.2%), coagulopathy in 16 (4%), cerebral venous sinus thrombosis (CVST) in 9
      (2.2%), thrombocytopenia in 3 (0.7%), vasculitis in 2 (0.5%) and cryptogenic in
      37 (9.2%) patients. The patients with cryptogenic ICH were younger, had better
      Glasgow coma scale (GCS) on admission and good outcome compared those with known
      etiology. The most common location of ICH was basal ganglion and thalamus
      (71.3%). 102 (25%) patients died, 161 (39.9%) had poor and 141 (34.9%) had good
      outcome. Hypertensive ICH patients had frequent death or disability (P<0.001). On
      multivariate analysis, low GCS score (P <0.001), large ICH (P=0.01) and high
      leukocyte count on admission (P=0.03) were significantly related to the 1 month
      mortality. CONCLUSION: Hypertension is the commonest cause of ICH in young Indian
      adults and its outcome is related to volume of ICH, GCS score and admission
      leukocyte count.

PMID- 24128696
TI  - NMCP/LINC proteins: putative lamin analogs in plants?
AB  - Lamins are the main components of the metazoan lamina, and while the organization
      of the nuclear lamina of metazoans and plants is similar, there are apparently no
      genes encoding lamins or most lamin-binding proteins in plants. Thus, the plant
      lamina is not lamin-based and the proteins that form this structure are still to
      be characterized. Members of the plant NMCP/LINC/CRWN protein family share the
      typical tripartite structure of lamins, although the 2 exhibit no sequence
      similarity. However, given the many similarities between NMCP/LINC/CRWN proteins
      and lamins (structural organization, position of conserved regions, sub-nuclear
      distribution, solubility, and pattern of expression), these proteins are good
      candidates to carry out the functions of lamins in plants. Moreover, functional
      analysis of NMCP/LINC mutants has revealed their involvement in maintaining
      nuclear size and shape, another activity fulfilled by lamins. This review
      summarizes the current understanding of NMCP/LINC proteins and discusses future
      studies that will be required to demonstrate definitively that these proteins are
      plant analogs of lamins.

PMID- 24128697
TI  - Autochthonous falciparum malaria possibly transmitted by luggage-carried vector
      in Paris, France, February 2013.
AB  - We report a case of autochthonous falciparum malaria in a patient in Paris,
      France, in February 2013 who reported no recent travel to malaria-endemic
      countries. The parasite, Plasmodium falciparum, was possibly transmitted by an
      infective Anopheles mosquito carried in baggage from a malaria-endemic area.

PMID- 24128698
TI  - Plasmodium knowlesi infection imported to Germany, January 2013.
AB  - Plasmodium knowlesi was known as a plasmodium of macaques until P. knowlesi
      transmission to humans was recognised in Borneo and later throughout South-East
      Asia. We describe here a case of a P. knowlesi infection imported to Germany from
      Thailand. The patient had not taken antimalarial chemoprophylaxis and suffered
      from daily fever attacks. Microscopy revealed trophozoites and gametocytes
      resembling P. malariae. P. knowlesi malaria was confirmed by PCR.

PMID- 24128699
TI  - Treatment outcome of multi-drug resistant tuberculosis in the United Kingdom:
      retrospective-prospective cohort study from 2004 to 2007.
AB  - United Kingdom (UK) guidelines recommend at least 18 months treatment for
      patients with multidrug-resistant tuberculosis (MDR-TB). Prior to 2008, data on
      treatment outcome were only available at 12 months and therefore the proportion
      completing treatment was unknown. This retrospective-prospective cohort study
      reports on treatment outcomes for MDR-TB patients notified between 2004 and 2007
      and examines factors associated with successful outcomes. 70.6% (144/204)
      completed treatment in 24 months or more, 6.9% (14) stopped treatment, 6.9% (14)
      died, 7.8% (16) were lost to follow up, 0.5% (1) relapsed and 4.4% (9) were
      transferred overseas. Following adjustment for age, being non-UK born, non
      compliance and having co-morbidities, treatment with a fluoroquinolone (OR 3.09;
      95% CI 1.21-7.88; p<0.05) or bacteriostatic drug (OR 4.23; 95% CI 1.60-11.18;
      p<0.05) were independently associated with successful treatment outcome.
      Treatment completion for MDR-TB cases remains below the World Health Organization
      (WHO) target. Our findings support current WHO guidelines for MDR-TB treatment.
      The UK should consider adopting individualised regimens based on WHO recommended
      drugs, taking into account drug sensitivities. Improving treatment completion
      rates will be key to tackling further drug resistance and transmission from
      untreated infectious cases.

PMID- 24128700
TI  - Incubation period for campylobacteriosis and its importance in the estimation of
      incidence related to travel.
AB  - Differentiation between travel-related and domestic cases of infectious disease
      is important in managing risk. Incubation periods of cases from several outbreaks
      of campylobacteriosis in Canada, Europe, and the United States with defined
      exposure time of less than 24 hours were collated to provide information on the
      incubation period distribution. This distribution was consistent across the
      varied outbreaks considered, with 84% (702/832) of cases having an incubation
      period of four days or less and 1% having an incubation period of eight days or
      more. The incubation period distribution was incorporated into a model for the
      number of travel-related cases presenting with symptom onset at given dates after
      return to their country of residence. Using New Zealand notification data between
      2006 and 2010 for cases who had undertaken foreign travel within 10 days prior to
      symptom onset, we found that 29.6% (67/227 cases; 95% confidence interval (CI):
      28.3-30.8%) of these cases were likely to have been domestic cases. When cases
      with symptom onset prior to arrival were included, the probable domestic cases
      represented 11.8% (67/571; 95% CI: 11.2-12.3%). Consideration of incubation time
      distributions and consistent collection of travel start/end dates with symptom
      onset dates would assist attribution of cases to foreign travel.

PMID- 24128704
TI  - Genomic selection for feed efficiency in dairy cattle.
AB  - Feed is a major component of variable costs associated with dairy systems and is
      therefore an important consideration for breeding objectives. As a result,
      measures of feed efficiency are becoming popular traits for genetic analyses.
      Already, several countries account for feed efficiency in their breeding
      objectives by approximating the amount of energy required for milk production,
      maintenance, etc. However, variation in actual feed intake is currently not
      captured in dairy selection objectives, although this could be possible by
      evaluating traits such as residual feed intake (RFI), defined as the difference
      between actual and predicted feed (or energy) intake. As feed intake is expensive
      to accurately measure on large numbers of cows, phenotypes derived from it are
      obvious candidates for genomic selection provided that: (1) the trait is
      heritable; (2) the reliability of genomic predictions are acceptable to those
      using the breeding values; and (3) if breeding values are estimated for heifers,
      rather than cows then the heifer and cow traits need to be correlated. The
      accuracy of genomic prediction of dry matter intake (DMI) and RFI has been
      estimated to be around 0.4 in beef and dairy cattle studies. There are
      opportunities to increase the accuracy of prediction, for example, pooling data
      from three research herds (in Australia and Europe) has been shown to increase
      the accuracy of genomic prediction of DMI from 0.33 within country to 0.35 using
      a three-country reference population. Before including RFI as a selection
      objective, genetic correlations with other traits need to be estimated. Weak
      unfavourable genetic correlations between RFI and fertility have been published.
      This could be because RFI is mathematically similar to the calculation of energy
      balance and failure to account for mobilisation of body reserves correctly may
      result in selection for a trait that is similar to selecting for reduced (or
      negative) energy balance. So, if RFI is to become a selection objective, then
      including it in an overall multi-trait selection index where the breeding
      objective is net profit is sensible, as this would allow genetic correlations
      with other traits to be properly accounted for. If genetic parameters are
      accurately estimated then RFI is a logical breeding objective. If there is
      uncertainty in these, then DMI may be preferable. 

PMID- 24128705
TI  - Protocol for concomitant temporomandibular joint custom-fitted total joint
      reconstruction and orthognathic surgery utilizing computer-assisted surgical
      simulation.
AB  - Clinicians who address temporomandibular joint (TMJ) pathology and dentofacial
      deformities surgically can perform the surgery in 1 stage or 2 separate stages.
      The 2-stage approach requires the patient to undergo 2 separate operations and
      anesthesia, significantly prolonging the overall treatment. However, performing
      concomitant TMJ and orthognathic surgery (CTOS) in these cases requires careful
      treatment planning and surgical proficiency in the 2 surgical areas. This article
      presents a new treatment protocol for the application of computer-assisted
      surgical simulation in CTOS cases requiring reconstruction with patient-fitted
      total joint prostheses. The traditional and new CTOS protocols are described and
      compared. The new CTOS protocol helps decrease the preoperative workup time and
      increase the accuracy of model surgery. 

PMID- 24128706
TI  - Exposed bone in bisphosphonate-related osteonecrosis of the jaws may be induced
      and maintained by localized microbial biofilm osteomyelitis.

PMID- 24128707
TI  - Adult immunization: the need to address.
AB  - Vaccination is recommended throughout life to prevent vaccine-preventable
      diseases and their sequel. The primary focus of vaccination programs has
      historically been directed to childhood immunizations. For adults, chronic
      diseases have been the primary focus of preventive and medical health care,
      though there has been increased emphasis on preventing infectious diseases. Adult
      vaccination coverage, however, remains low for most of the routinely recommended
      vaccines. Though adults are less susceptible to fall prey to traditional
      infectious agents, the probability of exposure to infectious agents has increased
      manifold owing to globalization and increasing travel opportunities both within
      and across the countries. Thus, there is an urgent need to address the problem of
      adult immunization. The adult immunization enterprise is more complex,
      encompassing a wide variety of vaccines and a very diverse target population.
      There is no coordinated public health infrastructure to support an adult
      immunization program as there is for children. Moreover, there is little
      coordination among adult healthcare providers in terms of vaccine provision.
      Substantial improvement in adult vaccination is needed to reduce the health
      consequences of vaccine-preventable diseases among adults. Routine assessment of
      adult patient vaccination needs, recommendation, and offer of needed vaccines for
      adults should be incorporated into routine clinical care of adults. 

PMID- 24128708
TI  - Therapeutic benefit of the anesthesiologist-patient relationship.
AB  - The psychologic effect of the preoperative visit by an anesthetist has been
      compared with the effect of pentobarbital for preanesthetic medication. Patients
      receiving pentobarbital 1 hour before an operation became drowsy but it could not
      be shown that they became calm. Patients who had received a visit by an
      anesthetist before operation (informing them about the events which were to occur
      on the day of operation and about the anesthetic to be administered) were not
      drowsy but were more likely to be calm on the day of operation. The importance of
      the preoperative visit probably explains, in part, the difficulties previous
      investigators have had in showing sedative effects from the barbiturates and
      narcotics before operation. The tremendous emotional significance to a patient of
      illness or an operation may explain why physicians are able to exert such
      influence upon their patients.

PMID- 24128710
TI  - Lung cancer-celebrating progress and acknowledging challenges.

PMID- 24128711
TI  - Application of high-resolution CT imaging data to lung cancer drug development:
      measuring progress: workshop IX.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death and a major public
      health challenge across the entire world. Computed tomography (CT) imaging of the
      lung is a rapidly improving medical imaging technique. Spiral CT has been
      reported to not only improve the early detection of lung cancer in screening high
      risk tobacco-exposed populations but also to assist in the clinical assessment of
      new agents for therapy in lung cancer. METHODS: The Prevent Cancer Foundation has
      sponsored a series of workshops to accelerate progress in using quantitative
      imaging to advance lung cancer research progress, of which this report summarizes
      the Ninth Workshop. The defining strategy of this forum to support innovation in
      quantitative research for early lung cancer management was to enable software
      validations by assembling collections of high-quality images for which long-term
      clinical follow-up is known. An additional approach was to define a process for
      high-quality and economical national implementation of lung cancer screening.
      Representatives from the Quantitative Imaging Biomarker Alliance, the
      International Association for the Study of Lung Cancer, the Lung Cancer Alliance,
      and other organizations outlined their efforts in this regard. A major
      opportunity exists to advance the dialogue on the use of quantitative imaging
      tools to cross-fertilize and accelerate image-processing research across lung
      cancer and chronic obstructive pulmonary disease (COPD). CONCLUSION: The use of
      high-resolution CT imaging provides a window into a much earlier stage of COPD as
      well as coronary artery disease, both being tobacco-induced diseases. Progress in
      this area was reviewed and opportunities for enhanced collaborative progress
      defined. Key sessions reviewed emerging developments with imaging technology and
      the infrastructure to support the storage and distribution of these high-content
      modalities. Cooperation among diverse collaborators is essential to enable the
      rapid organic evolution of this field, so that improved outcomes with lung
      cancer, artery disease, and COPD can be obtained.

PMID- 24128712
TI  - Clinical characteristics of patients with malignant pleural mesothelioma
      harboring somatic BAP1 mutations.
AB  - INTRODUCTION: Genomic studies of malignant pleural mesothelioma (MPM) have
      recently identified frequent mutations in the BRCA-associated protein 1(BAP1)
      gene. In uveal melanoma and clear cell renal cell carcinoma, BAP1 mutations are
      associated with poor outcomes but their clinical significance in MPM is unknown.
      We therefore undertook this study to define the characteristics of patients whose
      MPM tumors harbor somatic BAP1 mutation and to examine the relationship between
      BAP1 mutation and survival. METHODS: We reviewed the charts of 121 patients with
      MPM tumors diagnosed between 1991 and 2009 tested for BAP1 mutation, and
      extracted the following information: age at diagnosis, sex, histology, stage,
      smoking status, asbestos exposure, family or personal history of malignancy, and
      treatment including surgery, chemotherapy, and radiation as well as survival
      status. RESULTS: Twenty-four of the 121 tumors (20%) harbored somatic BAP1
      mutations. The percentage of current or former smokers among cases with BAP1
      mutations was significantly higher than in BAP1 wild-type cases, (75% versus 42%;
      p = 0.006). However, the types of nucleotide substitutions in BAP1 did not
      suggest that this association was because of a causative role of smoking in BAP1
      mutations. No other clinical feature was significantly different among those with
      and without BAP1 mutations in their MPM. There was also no difference in survival
      according to somatic BAP1 mutation status. CONCLUSION: There is no apparent
      distinct clinical phenotype for MPM with somatic BAP1 mutation. The significance
      of the more frequent history of smoking among patients with BAP1-mutated MPM
      warrants further study.

PMID- 24128713
TI  - Treatment-related toxicities in a phase II trial of dasatinib in patients with
      squamous cell carcinoma of the lung.
AB  - INTRODUCTION: Advanced squamous cell carcinoma (SqCC) of the lung carries a poor
      prognosis, and new therapeutic targets are needed. Several studies have examined
      dasatinib in non-small cell lung cancer; these report not only significant
      toxicities, but also responses in patients found to harbor mutations in discoidin
      domain receptor tyrosine kinase 2 or BRAF. An open-label phase II trial with
      dasatinib was carried out to determine the response rates in patients with SqCC
      who had previously failed standard chemotherapy and to correlate responses with
      patient genotype. METHODS: Patients were treated with dasatinib 140 mg daily in
      28-day cycles. Patients were included if they had stage IIIb/IV SqCC, Eastern
      Cooperative Oncology Group performance status of 0 or 1, and for whom treatment
      with standard chemotherapy had failed. RESULTS: The study was halted after
      enrolling five patients, all of whom were discontinued from the trial because of
      excess toxicity of dasatinib administered at 140 mg/day. The patients were
      treated for 9, 14, 24, 40, and 42 days. Three of five patients (60%) experienced
      grade 3 or more toxicities (dyspnea, fatigue, elevated level of aspartate
      transaminase, anorexia, nausea). Intolerable grade 2 pleural effusions were noted
      in two of five patients. Four of five patients died after 44, 52, 127, and 226
      days; one patient remains alive at 279 days. No deaths were associated with the
      study drug. CONCLUSIONS: Similar to other studies, this study too found that
      dasatinib administered at 140 mg/day for the treatment of advanced SqCC of the
      lung is associated with excess adverse events, so is not recommended in
      unselected patients. Further work to identify patients likely to benefit from
      dasatinib and to manage dasatinib-related toxicities is needed.

PMID- 24128714
TI  - Adequacy of lymph node transbronchial needle aspirates using convex probe
      endobronchial ultrasound for multiple tumor genotyping techniques in non-small
      cell lung cancer.
AB  - INTRODUCTION: Adequate tumor acquisition is essential to identify somatic
      molecular alterations in non-small-cell lung cancer (NSCLC), such as epidermal
      growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK)
      translocations. The success and failure rates for tumor genotyping of tissue
      obtained from fine-needle aspirates of nodal tissue using a convex probe
      endobronchial ultrasound (CP-EBUS) and other diagnostic modalities in routine
      NSCLC care have not been described. METHODS: Clinicopathologic data, tumor
      genotype success and failure rates were retrospectively compiled and analyzed
      from 207 patient-tumor samples sent for routine tumor genotype in clinical
      practice, including 42 patient-tumor samples obtained from hilar or mediastinal
      lymph nodes using CP-EBUS. RESULTS: The median age of the patients was 65 years,
      62.3% were women, 77.8% were white, 26.6% were never smokers, 73.9% had advanced
      NSCLC, and 84.1% had adenocarcinoma histology. Tumor tissue was obtained from CP
      EBUS-derived hilar or mediastinal nodes in 42 cases (20.2% of total). In this
      latter cohort, the overall success rate for EGFR mutation analysis was 95.2%, for
      Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation 90.5%, and for ALK
      fluorescence in situ hybridization 90.5%. In the complete 207 tumors, the success
      rate for EGFR was 92.3%, for KRAS 91.8%, and for ALK 89.9%. The failure rates
      were not significantly different when comparing CP-EBUS-derived nodal tissue
      versus all other samples or versus surgical biopsies of mediastinal nodes, but
      were significantly lower than image-guided percutaneous transthoracic core-needle
      biopsies. CONCLUSIONS: The success rate of multiple tumor genomic analyses
      techniques for EGFR, KRAS, and ALK gene abnormalities using routine lung cancer
      tissue samples obtained from hilar or mediastinal lymph nodes by means of CP-EBUS
      exceeds 90%, and this method of tissue acquisition is not inferior to other
      specimen types. Tumor genotype techniques are feasible in most CP-EBUS-derived
      samples and therefore further expansion of routine tumor genotype for the care of
      patients with NSCLC may be possible using targeted sample acquisition through CP
      EBUS.

PMID- 24128715
TI  - Clinicopathologic analysis of ROS1-rearranged non-small-cell lung cancer and
      proposal of a diagnostic algorithm.
AB  - INTRODUCTION: We sought to evaluate the clinical and pathological characteristics
      of patients with non-small-cell lung cancer (NSCLC) that harbored a ROS1
      rearrangement. METHODS: Four hundred fifty-one Korean patients with resected
      NSCLC (the resected group) were examined for ROS1 rearrangements using a tissue
      microarray and ROS1 fluorescence in situ hybridization and analyzed for clinical
      and pathological features. Sixty-four patients with advanced pulmonary
      adenocarcinoma with no known oncogenic aberrations (the advanced group) were also
      screened for ROS1 rearrangements. RESULTS: Of the 451 consecutive patients from
      the resected group, ROS1 rearrangements were detected in eight cases (1.8%). In
      the advanced group, an additional eight patients (12.5%) were identified as
      harboring ROS1 rearrangements. ROS1 rearrangement was detected exclusively in
      adenocarcinomas and occurred more frequently in women than in men. With the
      exception of one patient with an EGFR deletion mutation in exon 19, ROS1-positive
      adenocarcinomas in all patients revealed no alterations in ALK, EGFR, KRAS, or
      MET genes. Most ROS1-rearranged tumors showed solid and papillary patterns.
      CONCLUSIONS: ROS1 rearrangements were detected in 1.8% of patients with resected
      NSCLC and were detected exclusively in adenocarcinomas, which is similar to the
      frequency detected in non-Asian patients. We suggest that ROS1 screening in
      adenocarcinoma patients with no known oncogenic aberrations is an effective
      strategy to find ROS1 rearrangements in NSCLC.

PMID- 24128716
TI  - Whole-genome sequencing analysis identifies a distinctive mutational spectrum in
      an arsenic-related lung tumor.
AB  - INTRODUCTION: Arsenic exposure is a significant cause of lung cancer in North
      America and worldwide. Arsenic-related tumors are structurally indistinguishable
      from those induced by other carcinogens. Because carcinogens, like tobacco,
      induce distinctive mutational signatures, we sought to characterize the
      mutational signature of an arsenic-related lung tumor from a never smoker with
      the use of whole-genome sequencing. METHODS: Tumor and lung tissues were obtained
      from a never smoker with lung squamous cell carcinoma (LUSC), without familiar
      history of lung cancer and chronically exposed to high levels of arsenic
      contaminated drinking water. The Illumina HiSeq-2000 platform was used to
      sequence each genome at approximately 30-fold haploid coverage. The mutational
      signature was compared with those observed in previously characterized lung
      tumors. RESULTS: The arsenic-related tumor exhibited alterations common in LUSC,
      such as the increased number of copies at 3q26 (SOX2 locus). However, the arsenic
      related genome not only harbored a lower number of point mutations, but also had
      a remarkably high fraction of T>G/A>C mutations and low fraction of C>A/G>T
      transversions, which is uncharacteristic of LUSCs. Furthermore, at the gene
      level, we identified a rare G>C mutation in TP53, which is uncommon in lung
      tumors in general (<0.2%) but has been observed in other arsenic-related
      malignancies. CONCLUSIONS: We generated the first whole-genome sequence of an
      LUSC from a never-smoker patient chronically exposed to arsenic, and identified a
      distinct mutational spectrum associated with arsenic exposure, providing novel
      evidence supporting the hypothesis that arsenic-induced lung tumors arise through
      molecular mechanisms that differ from those of the common lung cancer.

PMID- 24128717
TI  - PET/CT findings for bone marrow carcinosis because of lung adenocarcinoma.

PMID- 24128718
TI  - Improved survival associated with neoadjuvant chemoradiation in patients with
      clinical stage IIIA (N2) non-small-cell lung cancer.

PMID- 24128719
TI  - In response.

PMID- 24128720
TI  - Overdiagnosis in lung cancer screening with low-dose computed tomography.

PMID- 24128721
TI  - In response.

PMID- 24128722
TI  - Do mutations of the enhancer of zeste homolog 2 gene exist in small-cell lung
      cancer?

PMID- 24128723
TI  - In response.

PMID- 24128724
TI  - Pulmonary atelectasis after stereotactic ablative radiotherapy for a central lung
      tumor.

PMID- 24128725
TI  - Dramatic response to crizotinib in an ALK-positive adenocarcinoma patient with
      disseminated intravascular coagulation.

PMID- 24128726
TI  - Radiochemotherapy in clinical stage IIIA non-small cell lung cancer: effective
      and low toxic standard treatment option (in the absence of other proven
      treatments).

PMID- 24128727
TI  - In response.

PMID- 24128728
TI  - Contribution to the understanding of the cycle of the protozoan parasite
      Marteilia refringens.
AB  - The paramyxean parasite Marteilia refringens infects several bivalve species
      including European flat oysters Ostrea edulis and Mediterranean mussels Mytilus
      galloprovincialis. Sequence polymorphism allowed definition of three parasite
      types 'M', 'O' and 'C' preferably detected in oysters, mussels and cockles
      respectively. Transmission of the infection from infected bivalves to copepods
      Paracartia grani could be experimentally achieved but assays from copepods to
      bivalves failed. In order to contribute to the elucidation of the M. refringens
      life cycle, the dynamics of the infection was investigated in O. edulis, M.
      galloprovincialis and zooplankton over one year in Diana lagoon, Corsica
      (France). Flat oysters appeared non-infected while mussels were infected part of
      the year, showing highest prevalence in summertime. The parasite was detected by
      PCR in zooplankton particularly after the peak of prevalence in mussels. Several
      zooplanktonic groups including copepods, Cladocera, Appendicularia, Chaetognatha
      and Polychaeta appeared PCR positive. However, only the copepod species
      Paracartia latisetosa showed positive signal by in situ hybridization. Small
      parasite cells were observed in gonadal tissues of female copepods demonstrating
      for the first time that a copepod species other than P. grani can be infected
      with M. refringens. Molecular characterization of the parasite infecting mussels
      and zooplankton allowed the distinguishing of three Marteilia types in the
      lagoon.

PMID- 24128729
TI  - Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker
      approach.
AB  - Bio-monitoring of human exposure to mycotoxin has mostly been limited to a few
      individually measured mycotoxin biomarkers. This study aimed to determine the
      frequency and level of exposure to multiple mycotoxins in human urine from
      Cameroonian adults. 175 Urine samples (83% from HIV-positive individuals) and
      food frequency questionnaire responses were collected from consenting
      Cameroonians, and analyzed for 15 mycotoxins and relevant metabolites using LC
      ESI-MS/MS. In total, eleven analytes were detected individually or in
      combinations in 110/175 (63%) samples including the biomarkers aflatoxin M1,
      fumonisin B1, ochratoxin A and total deoxynivalenol. Additionally, important
      mycotoxins and metabolites thereof, such as fumonisin B2, nivalenol and
      zearalenone, were determined, some for the first time in urine following dietary
      exposures. Multi-mycotoxin contamination was common with one HIV-positive
      individual exposed to five mycotoxins, a severe case of co-exposure that has
      never been reported in adults before. For the first time in Africa or elsewhere,
      this study quantified eleven mycotoxin biomarkers and bio-measures in urine from
      adults. For several mycotoxins estimates indicate that the tolerable daily intake
      is being exceeded in this study population. Given that many mycotoxins adversely
      affect the immune system, future studies will examine whether combinations of
      mycotoxins negatively impact Cameroonian population particularly immune
      suppressed individuals. 

PMID- 24128730
TI  - TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring
      degradation by selective autophagy.
AB  - Upon completion of cytokinesis, the midbody ring is transported asymmetrically
      into one of the two daughter cells where it becomes a midbody ring derivative
      that is degraded by autophagy. In this study we showed that the ubiquitin-binding
      autophagy receptor SQSTM1/p62 and the interacting adaptor protein WDFY3/ALFY form
      a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as
      NBR1, are important for efficient clearance of midbody ring derivatives by
      autophagy. The number of ubiquitinated midbody ring derivatives decreases in
      TRAF6-depleted cells and we showed that TRAF6 mediates ubiquitination of the
      midbody ring localized protein KIF23/MKLP1. We conclude that TRAF6-mediated
      ubiquitination of the midbody ring is important for its subsequent recognition by
      ubiquitin-binding autophagy receptors and degradation by selective autophagy.

PMID- 24128732
TI  - Carbon monoxide poisoning in patients presenting to the emergency department with
      a headache in winter months.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning is an important reason for emergency
      department (ED) visits during winter months, but because there are no specific
      symptoms it can be difficult to diagnose. We aimed to determine the frequency of
      CO poisoning in patients presenting to the ED with headaches during winter months
      and evaluate the ability of non-invasive carboxyhaemoglobin measurement (SpCO) to
      screen for CO poisoning in these patients. METHODS: SpCO measurement values of
      adult patients were measured non-invasively with a Rad-57 Pulse CO-Oximeter.
      Patients whose initial SpCO reading was over 10% underwent a venous blood draw
      for laboratory determination of invasive carboxyhaemoglobin (COHb) measurement.
      Patients with a invasive COHb level of over 10% were diagnosed with CO poisoning.
      Percentage of screened patients with suspected and occult CO poisoning, the
      distribution of patients with CO poisoning by time of day of the ED visit and the
      positive predictive value of SpCO to detect CO poisoning were calculated.
      RESULTS: 483 patients presenting with headaches were screened with SpCO
      measurement. Thirty-eight had a mean SpCO value of over 10%, 31 (6.4% of the
      study population) of which had elevated COHb confirmed by laboratory
      determination. SpCO measurement, therefore, had a positive predictive value of
      82% for CO poisoning. Twenty-four (77%) of the CO poisoning cases were suspected
      and seven (23%) were occult. CO poisoning was detected more frequently in
      patients visiting the ED after midnight and during morning hours. CONCLUSIONS: CO
      poisoning should be kept in mind in patients presenting to the ED with a
      headache. SpCO is an effective screening tool to detect CO poisoning in these
      patients.

PMID- 24128731
TI  - The Ibero-American transcatheter aortic valve implantation registry with the
      CoreValve prosthesis. Early and long-term results.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the recommended
      therapy for patients with severe aortic stenosis who are not suitable candidates
      for surgery. The aim of this study was to describe early experience and long-term
      follow-up with the CoreValve self-expanding aortic prosthesis at 42 Ibero
      American hospitals. METHODS: Multiple centre observational study including 1220
      consecutive patients with symptomatic severe aortic stenosis who are not suitable
      candidates for surgery and underwent transcatheter aortic valve implantation with
      the self-expanding Medtronic CoreValve System between December 2007 and May 2012.
      RESULTS: The registry included 1220 consecutive patients with a mean age of 80.8
      +/- 6.3 years and a mean logistic euroSCORE of 17.8% +/- 13%. The procedural
      success rate was 96.1%. Hospital mortality was 7.3% and combined end-point was
      21.3%. Aortic regurgitation after TAVI was present in 24.5% (Sellers grade >= 2).
      The estimated 1-year and 2-year survival rates were 82.1% and 73.4% respectively.
      The following issues were significant independent risk factors for hospital
      mortality: acute kidney failure (odds ratio 3.55); stroke (odds ratio 5.72);
      major bleeding (odds ratio 2.64) and euroSCORE (odds ratio 1.02). Long-term
      predictors of mortality were diabetes mellitus (hazard ratio 1.59, 95% confidence
      interval 1.09-2.31), severe chronic obstructive pulmonary disease (hazard ratio
      1.85, 95% confidence interval 1.85-2.88), and functional classes NYHA III-IV
      (hazard ratio 1.31, 95% confidence interval 1.01-1.70). CONCLUSIONS:
      Transcatheter aortic valve implantation constitutes a safe and viable therapeutic
      option for high operative risk patients with severe aortic stenosis. Long-term
      prognosis is conditioned by associate comorbidities.

PMID- 24128734
TI  - Quantification of the impact of a confounding variable on functional connectivity
      confirms anti-correlated networks in the resting-state.
AB  - The effect of regressing out the global average signal (GAS) in resting state
      fMRI data has become a concern for interpreting functional connectivity analyses.
      It is not clear whether the reported anti-correlations between the Default Mode
      and the Dorsal Attention Networks are intrinsic to the brain, or are artificially
      created by regressing out the GAS. Here we introduce a concept, Impact of the
      Global Average on Functional Connectivity (IGAFC), for quantifying the
      sensitivity of seed-based correlation analyses to the regression of the GAS. This
      voxel-wise IGAFC index is defined as the product of two correlation coefficients:
      the correlation between the GAS and the fMRI time course of a voxel, times the
      correlation between the GAS and the seed time course. This definition enables the
      calculation of a threshold at which the impact of regressing-out the GAS would be
      large enough to introduce spurious negative correlations. It also yields a post
      hoc impact correction procedure via thresholding, which eliminates spurious
      correlations introduced by regressing out the GAS. In addition, we introduce an
      Artificial Negative Correlation Index (ANCI), defined as the absolute difference
      between the IGAFC index and the impact threshold. The ANCI allows a graded
      confidence scale for ranking voxels according to their likelihood of showing
      artificial correlations. By applying this method, we observed regions in the
      Default Mode and Dorsal Attention Networks that were anti-correlated. These
      findings confirm that the previously reported negative correlations between the
      Dorsal Attention and Default Mode Networks are intrinsic to the brain and not the
      result of statistical manipulations. Our proposed quantification of the impact
      that a confound may have on functional connectivity can be generalized to global
      effect estimators other than the GAS. It can be readily applied to other
      confounds, such as systemic physiological or head movement interferences, in
      order to quantify their impact on functional connectivity in the resting state. 

PMID- 24128733
TI  - The use of near-infrared spectroscopy in the study of typical and atypical
      development.
AB  - The use of functional near infrared spectroscopy (fNIRS) has grown exponentially
      over the past decade, particularly among investigators interested in early brain
      development. The use of this neuroimaging technique has begun to shed light on
      the development of a variety of sensory, perceptual, linguistic, and social
      cognitive functions. Rather than cast a wide net, in this paper we first discuss
      typical development, focusing on joint attention, face processing, language, and
      sensorimotor development. We then turn our attention to infants and children
      whose development has been compromised or who are at risk for atypical
      development. We conclude our review by critiquing some of the methodological
      issues that have plagued the extant literature as well as offer suggestions for
      future research. 

PMID- 24128735
TI  - Understanding the contribution of neural and physiological signal variation to
      the low repeatability of emotion-induced BOLD responses.
AB  - Previous studies have reported low repeatability of BOLD activation measures
      during emotion processing tasks. It is not clear, however, whether low
      repeatability is a result of changes in the underlying neural signal over time,
      or due to insufficient reliability of the acquired BOLD signal caused by noise
      contamination. The aim of this study was to investigate the influence of
      "cleaning" the BOLD signal, by correcting for physiological noise and for
      differences in BOLD responsiveness, on measures of repeatability. Fifteen healthy
      volunteers were scanned on two different occasions, performing an emotion
      provocation task with faces (neutral, 50% fearful, 100% fearful) followed by a
      breath-hold paradigm to provide a marker of BOLD responsiveness. Repeatability of
      signal distribution (spatial repeatability) and repeatability of signal amplitude
      within two regions of interest (amygdala and fusiform gyrus) were estimated by
      calculating the intraclass correlation coefficient (ICC). Significant
      repeatability of signal amplitude was only found within the right amygdala during
      the perception of 50% fearful faces, but disappeared when physiological noise
      correction was performed. Spatial repeatability was higher within the fusiform
      gyrus than within the amygdala, and better at the group level than at the
      participant level. Neither physiological noise correction, nor consideration of
      BOLD responsiveness, assessed through the breath-holding, increased
      repeatability. The findings lead to the conclusion that low repeatability of BOLD
      response amplitude to emotional faces is more likely to be explained by the lack
      of stability in the underlying neural signal than by physiological noise
      contamination. Furthermore, reported repeatability might be a result of
      repeatability of task-correlated physiological variation rather than neural
      activity. This means that the emotion paradigm used in this study might not be
      useful for studies that require the BOLD response to be a stable measure of
      emotional processing, for example in the context of biomarkers. 

PMID- 24128736
TI  - Epilepsy surgery outcome and functional network alterations in longitudinal MEG:
      a minimum spanning tree analysis.
AB  - Seizure freedom after resective epilepsy surgery is not obtained in a substantial
      number of patients with medically intractable epilepsy. Functional neural network
      analysis is a promising technique for more accurate identification of the target
      areas for epilepsy surgery, but a better understanding of the correlations
      between changes in functional network organization due to surgery and
      postoperative seizure status is required. We explored these correlations in
      longitudinal magnetoencephalography (MEG) recordings of 20 lesional epilepsy
      patients. Resting-state MEG recordings were obtained at baseline (preoperatively;
      T0) and at 3-7 (T1) and 9-15months after resection (T2). We assessed frequency
      specific functional connectivity and performed a minimum spanning tree (MST)
      network analysis. The MST captures the most important connections in the network.
      We found a significant positive correlation between functional connectivity in
      the lower alpha band and seizure frequency at T0, especially in regions where
      lesions were located. MST leaf fraction, a measure of integration of information
      in the network, was significantly increased between T0 and T2, only for the
      seizure-free patients. This is in line with previous work, which showed that
      lower functional network integration in lesional epilepsy patients is related to
      higher epilepsy burden. Finally, eccentricity and betweenness centrality, which
      are measures of hub-status, decreased between T0 and T2 in seizure free patients,
      also in regions that were anatomically close to resection cavities. Our results
      increase insight into functional network changes in successful epilepsy surgery
      and might eventually be utilized for optimization of neurosurgical approaches. 

PMID- 24128737
TI  - Genetic effects on the cerebellar role in working memory: same brain, different
      genes?
AB  - Over the past several years, evidence has accumulated showing that the cerebellum
      plays a significant role in cognitive function. Here we show, in a large
      genetically informative twin sample (n=430; aged 16-30years), that the cerebellum
      is strongly, and reliably (n=30 rescans), activated during an n-back working
      memory task, particularly lobules I-IV, VIIa Crus I and II, IX and the vermis.
      Monozygotic twin correlations for cerebellar activation were generally much
      larger than dizygotic twin correlations, consistent with genetic influences.
      Structural equation models showed that up to 65% of the variance in cerebellar
      activation during working memory is genetic (averaging 34% across significant
      voxels), most prominently in the lobules VI, and VIIa Crus I, with the remaining
      variance explained by unique/unshared environmental factors. Heritability
      estimates for brain activation in the cerebellum agree with those found for
      working memory activation in the cerebral cortex, even though cerebellar cyto
      architecture differs substantially. Phenotypic correlations between BOLD percent
      signal change in cerebrum and cerebellum were low, and bivariate modeling
      indicated that genetic influences on the cerebellum are at least partly specific
      to the cerebellum. Activation on the voxel-level correlated very weakly with
      cerebellar gray matter volume, suggesting specific genetic influences on the BOLD
      signal. Heritable signals identified here should facilitate discovery of genetic
      polymorphisms influencing cerebellar function through genome-wide association
      studies, to elucidate the genetic liability to brain disorders affecting the
      cerebellum. 

PMID- 24128738
TI  - On the neural origin of pseudoneglect: EEG-correlates of shifts in line bisection
      performance with manipulation of line length.
AB  - Healthy participants tend to show systematic biases in spatial attention, usually
      to the left. However, these biases can shift rightward as a result of a number of
      experimental manipulations. Using electroencephalography (EEG) and a computerized
      line bisection task, here we investigated for the first time the neural
      correlates of changes in spatial attention bias induced by line-length (the so
      called line-length effect). In accordance with previous studies, an overall
      systematic left bias (pseudoneglect) was present during long line but not during
      short line bisection performance. This effect of line-length on behavioral bias
      was associated with stronger right parieto-occipital responses to long as
      compared to short lines in an early time window (100-200ms) post-stimulus onset.
      This early differential activation to long as compared to short lines was task
      independent (present even in a non-spatial control task not requiring line
      bisection), suggesting that it reflects a reflexive attentional response to long
      lines. This was corroborated by further analyses source-localizing the line
      length effect to the right temporo-parietal junction (TPJ) and revealing a
      positive correlation between the strength of this effect and the magnitude by
      which long lines (relative to short lines) drive a behavioral left bias across
      individuals. Therefore, stimulus-driven left bisection bias was associated with
      increased right hemispheric engagement of areas of the ventral attention network.
      This further substantiates that this network plays a key role in the genesis of
      spatial bias, and suggests that post-stimulus TPJ-activity at early information
      processing stages (around the latency of the N1 component) contributes to the
      left bias. 

PMID- 24128739
TI  - Brain activation related to the perception of minimal agency cues: the role of
      the mirror system.
AB  - Recent fMRI studies indicate that the posterior superior temporal sulcus (pSTS)
      and the mirror system are involved in analyzing goal-directed actions performed
      by non-human objects. However, these studies have some limitations: the
      animations showed moving shapes that resemble humans and human movement, or
      showed the interaction of two moving shapes rather than one alone. This may have
      prompted participants to assume a human agent instead of an object. To avoid this
      potential confound, in this study, animations showed a small circular shape
      (agent) jumping toward a bigger circular shape (goal) with an obstacle separating
      them. We manipulated agency of the small circular shape by showing its movements
      as self-propelled (Agent condition) or as launched by a lever mechanism (Non
      agent condition). The small shape succeeded in avoiding an obstacle and reaching
      the goal object or failed to do so. Our results showed that goal-directed actions
      performed by an agentic shape recruited the mirror system (the inferior parietal
      lobe and the premotor cortex) in comparison with shapes that were launched.
      Success or failure to avoid the obstacle had no effect on these areas. These
      results complement and further extend previous findings indicating that the
      mirror system does not appear to be selective for biological actions and their
      goals, nor does it require the presence of a human, human body parts or human
      made objects. Instead, it seems to play a general role in representing goal
      directed actions of agents regardless of their form. 

PMID- 24128741
TI  - Factors predictive of immediate breast reconstruction following mastectomy for
      invasive breast cancer in Australia.
AB  - PURPOSE: To investigate person, cancer and treatment determinants of immediate
      breast reconstruction (IBR) in Australia. METHODS: Bi-variable and multi-variable
      analyses of the Quality Audit database. RESULTS: Of 12,707 invasive cancers
      treated by mastectomy circa 1998-2010, 8% had IBR. This proportion increased over
      time and reduced from 29% in women below 30 years to approximately 1% in those
      aged 70 years or more. Multiple regression indicated that other IBR predictors
      included: high socio-economic status; private health insurance; being
      asymptomatic; a metropolitan rather than inner regional treatment centre; higher
      surgeon case load; small tumour size; negative nodal status, positive
      progesterone receptor status; more cancer foci; multiple affected breast
      quadrants; synchronous bilateral cancer; not having neo-adjuvant chemotherapy,
      adjuvant radiotherapy or adjuvant hormone therapy; and receiving ovarian
      ablation. CONCLUSIONS: Variations in access to specialty services and other
      possible causes of variations in IBR rates need further investigation.

PMID- 24128740
TI  - Selection and stopping in voluntary action: a meta-analysis and combined fMRI
      study.
AB  - Voluntary action control requires selection of appropriate responses and stopping
      of inappropriate responses. Selection and stopping are often investigated
      separately, but they appear to recruit similar brain regions, including the pre
      supplementary motor area (preSMA) and inferior frontal gyrus. We therefore
      examined the evidence for overlap of selection and stopping using two approaches:
      a meta-analysis of existing studies of selection and stopping, and a novel within
      subject fMRI study in which action selection and a stop signal task were combined
      factorially. The novel fMRI study also permitted us to investigate hypotheses
      regarding a common mechanism for selection and stopping. The preSMA was
      identified by both methods as common to selection and stopping. However, stopping
      a selected action did not recruit preSMA more than stopping a specified action,
      nor did stop signal reaction times differ significantly across the two
      conditions. These findings suggest that the preSMA supports both action selection
      and stopping, but the two processes may not require access to a common inhibition
      mechanism. Instead, the preSMA might represent information about potential
      actions that is used in both action selection and stopping in order to resolve
      conflict between competing available responses. 

PMID- 24128742
TI  - Life cycle of Cryptosporidium muris in two rodents with different responses to
      parasitization.
AB  - This study focuses on mapping the life cycle of Cryptosporidium muris in two
      laboratory rodents; BALB/c mice and the southern multimammate rat Mastomys
      coucha, differing in their prepatent and patent periods. Both rodents were
      simultaneously experimentally inoculated with viable oocysts of C. muris (strain
      TS03). Animals were dissected and screened for the presence of the parasite using
      a combined morphological approach and nested PCR (SSU rRNA) at different times
      after inoculation. The occurrence of first developmental stages of C. muris in
      stomach was detected at 2.5 days post-infection (dpi). The presence of Type II
      merogony, appearing 36 h later than Type I merogony, was confirmed in both
      rodents. Oocysts exhibiting different size and thickness of their wall were
      observed from 5 dpi onwards in stomachs of both host models. The early phase of
      parasitization in BALB/c mice progressed rapidly, with a prepatent period of 7.5
      10 days; whereas in M. coucha, the developmental stages of C. muris were first
      observed 12 h later in comparison with BALB/c mice and prepatent period was
      longer (18-21 days). Similarly, the patent periods of BALB/c mice and M. coucha
      differed considerably, i.e. 10-15 days vs chronic infection throughout the life
      of the host, respectively.

PMID- 24128743
TI  - All contraceptives are not created equal.

PMID- 24128744
TI  - Reductions in Medicare payments and patient outcomes: an analysis of 5 leading
      Medicare conditions.
AB  - BACKGROUND: The Affordable Care Act enacted significant Medicare payment
      reductions to providers, yet the effects of such major reductions on patients
      remain unclear. We used the Balanced Budget Act (BBA) of 1997 as a natural
      experiment to study the long-term consequence of major payment reductions on
      patient outcomes. OBJECTIVES: To analyze whether mortality trends diverge over
      the years between hospitals facing different levels of payment cuts because of
      the BBA for 5 leading conditions: acute myocardial infarction, congestive heart
      failure, stroke, pneumonia, and hip fracture. RESEARCH DESIGN: Using 100%
      Medicare claims between 1995 and 2005, hospital database, and published reports
      on BBA policy components, we compared changes in outcomes between hospitals
      facing small and large BBA payment reductions across 3 periods (pre-BBA, initial
      BBA, and post-BBA) using instrumental variable hospital fixed-effects regression
      models. SETTING: All general, acute, nonrural, short-stay hospitals in the United
      States 1995-2005. MAIN OUTCOME MEASURES: Hospital risk-adjusted mortality rates
      (7, 30, 90 d, and 1 y). RESULTS: Mortality trends between hospitals in small and
      large payment-cut categories were similar between pre-BBA and initial-BBA
      periods, but diverged in the post-BBA period. Relative to the small-cut
      hospitals, hospitals in the large-cut category experienced smaller decline in 1
      year mortality rates in the post-BBA period compared with their pre-BBA trends by
      0.8-1.4 percentage points, depending on the condition (P<0.05 for all conditions,
      except for hip fracture). CONCLUSION: We found consistent evidence across
      multiple conditions that reductions in Medicare payments are associated with
      slower improvement in mortality outcomes.

PMID- 24128745
TI  - Impact of changes in Medicaid coverage on physician provision of safety net care.
AB  - BACKGROUND: The Patient Protection and Affordable Care Act will expand Medicaid
      coverage substantially, with the goal of improving the health of low-income
      individuals and reducing disparities in coverage and access. Whether insurance
      expansions are successful in achieving this goal will depend in part on physician
      response to changes in insurance coverage mix and the effect of this response on
      access to care for low-income safety net populations. OBJECTIVES: The objective
      of the study was to consider the impact of changes in market-level Medicaid
      coverage on measures of physician participation in care for safety net
      populations. RESEARCH DESIGN: We use 4 waves of the Community Tracking Study
      Physician Survey from 1996 to 2005. We estimate both market-level and physician
      level fixed effects models, to consider changes in market-level Medicaid rates on
      measures of physician acceptance of new patients (both Medicaid patients and
      uninsured patients unable to pay), revenue from Medicaid, and provision of
      charity care. We also stratify the sample to investigate whether effects differ
      among office-based versus facility-based physicians. RESULTS: Increases in
      Medicaid coverage are associated with statistically significant decreases in the
      likelihood that physicians will accept new uninsured patients who are unable to
      pay, particularly among office-based physicians. Increases in Medicaid coverage
      are not associated with changes in acceptance of new Medicaid patients.
      CONCLUSIONS: Past changes in Medicaid coverage rates are not associated with
      changes in physician acceptance of new Medicaid patients or provision of charity
      care, although they are associated with lower acceptance of new uninsured
      patients, particularly among office-based physicians.

PMID- 24128747
TI  - Interactive voice technology (IVR) is widely applicable.

PMID- 24128746
TI  - Thirty years of disparities intervention research: what are we doing to close
      racial and ethnic gaps in health care?
AB  - BACKGROUND: A systematic scan of the disparities intervention literature will
      allow researchers, providers, and policymakers to understand which interventions
      are being evaluated to improve minority health and which areas require further
      research. METHODS: We systematically categorized 391 disparities intervention
      articles published between 1979 and 2011, covering 11 diseases. We developed a
      taxonomy of disparities interventions using qualitative theme analysis. We
      identified the tactic, or what was done to intervene; the strategy, or a group of
      tactics with common characteristics; and the level, or who was targeted by the
      effort. RESULTS: The taxonomy included 44 tactics, 9 strategies, and 6 levels.
      Delivering education and training was the most common strategy (37%). Within
      education and training, the most common tactics were education about disease
      (14%) and self-management (11%), whereas communication skills training (3%) and
      decision-making aids (1%) were less frequent. The strategy of actively engaging
      the community through tactics such as community health workers and outreach
      efforts accounted for 6.5% of tactics. Interventions most commonly targeted
      patients (50%) and community members who were not established patients of the
      intervening organization (32%). Interventions targeting providers (7%), the
      microsystem (immediate care team) (9%), organizations (3%), and policies (0.1%)
      were less common. CONCLUSIONS: Disparities researchers have predominantly focused
      on the patient as the target for change; future research should also investigate
      how to improve the system that serves minority patients. Areas for further study
      include interventions that engage the community, educational interventions that
      address communication barriers, and the impact of policy reform on disparities in
      care.

PMID- 24128748
TI  - Odontometric sex variation in Malaysians with application to sex prediction.
AB  - Information about the sex of individuals is important for human identification.
      This study was conducted to quantify classification rates of sex prediction
      models for Malaysians using odontometric profiles. Mesiodistal (MD) and
      buccolingual (BL) crown dimensions of the permanent dentition were studied in 400
      young adult Malaysians, giving a total of 28 tooth size variables. The sample
      consisted of three major ethnic groups, the Malays, Chinese and Tamils, since the
      aim was to assess sex dimorphism in Malaysians as a whole. Results showed that
      the mesiodistal diameter of the lower canine was the most sexually dimorphic
      dimension in Malaysian Malays and Tamils. Univariate analyses showed that the
      magnitude and pattern of sex dimorphism varies between these three ethnic groups,
      with Malaysian Chinese and Tamils being more dimorphic than the Malaysian Malays.
      Stepwise discriminant functions were generated bearing in mind their application
      in practical forensic situations. The range of classification rates was from
      70.2% to 78.5% for the composite Malaysian group, and 83.8%, 77.9%, 72.4% for
      Malaysian Chinese, Malays and Tamils, respectively. The 'Area Under the Receiver
      Operating Characteristic Curve statistics' indicated good classification rates
      for three prediction models obtained using a combination of all tooth size
      variables, mandibular teeth, and mesiodistal dimensions in the composite
      Malaysian group, and for all tooth size variables in each ethnic group. The
      present study provides strong support for the value of odontometry as an adjunct
      scientific method for sex prediction in human identification. 

PMID- 24128750
TI  - Repeated acidosis challenges and live yeast supplementation shape rumen
      microbiota and fermentations and modulate inflammatory status in sheep.
AB  - This study aimed to investigate the impact of repeated acidosis challenges (ACs)
      and the effect of live yeast supplementation (Saccharomyces cerevisiae I-1077,
      SC) on rumen fermentation, microbial ecosystem and inflammatory response. The
      experimental design involved two groups (SC, n=6; Control, n=6) of rumen
      fistulated wethers that were successively exposed to three ACs of 5 days each,
      preceded and followed by resting periods (RPs) of 23 days. AC diets consisted of
      60% wheat-based concentrate and 40% hay, whereas RPs diets consisted of 20%
      concentrate and 80% hay. ACs induced changes in rumen fermentative parameters
      (pH, lactate and volatile fatty-acid concentrations and proportions) as well as
      in microbiota composition and diversity. The first challenge drove the
      fermentation pattern towards propionate. During successive challenges, rumen pH
      measures worsened in the control group and the fermentation profile was
      characterised by a higher butyrate proportion and changes in the microbiota. The
      first AC induced a strong release of rumen histamine and lipopolysaccharide that
      triggered the increase of acute-phase proteins in the plasma. This inflammatory
      status was maintained during all AC repetitions. Our study suggests that the
      response of sheep to an acidosis diet is greatly influenced by the feeding
      history of individuals. In live yeast-supplemented animals, the first AC was as
      drastic as in control sheep. However, during subsequent challenges, yeast
      supplementation contributed to stabilise fermentative parameters, promoted
      protozoal numbers and decreased lactate producing bacteria. At the systemic
      level, yeast helped normalising the inflammatory status of the animals. 

PMID- 24128751
TI  - The antinociceptive effects of intracerebroventricular administration of Chicago
      sky blue 6B, a vesicular glutamate transporter inhibitor.
AB  - Accumulating evidence suggests that vesicular glutamate transporters (VGLUTs),
      which control the storage and release of glutamate, may play a role in pain
      processing. Chicago sky blue 6B (CSB6B), which is structurally related to
      glutamate, is a competitive VGLUT inhibitor without affecting plasma membrane
      transporters. The present study was designed to investigate the antinociceptive
      effects of CSB6B in a number of pain models. The hot-plate test was used as an
      acute thermal pain test. Inflammatory pain was evaluated using acetic acid
      writhing, formalin, and complete Freund's adjuvant tests. Intracerebroventricular
      administration of CSB6B did not affect acute thermal pain responses in 50 or 55
      degrees C hot plate tests. However, CSB6B attenuated acetic acid-induced writhing
      in a dose-dependent and time-dependent manner. In addition, CSB6B reduced
      licking/biting behavior during the second phase, but not during the first phase,
      following an intraplantar injection of formalin. In the complete Freund's
      adjuvant test, a significant attenuation of thermal hyperalgesia was also
      observed in CSB6B-treated mice. At antinociceptive doses, CSB6B did not affect
      mice spontaneous locomotor activity. The present study shows that pharmacological
      inhibition of VGLUT activity was sufficient to attenuate experimental
      inflammatory pain and suggests that regulation of VGLUTs might be a novel
      therapeutic strategy for the treatment of pain. 

PMID- 24128749
TI  - Buckling of a growing tissue and the emergence of two-dimensional patterns.
AB  - The process of biological growth and the associated generation of residual stress
      has previously been considered as a driving mechanism for tissue buckling and
      pattern selection in numerous areas of biology. Here, we develop a two
      dimensional thin plate theory to simulate the growth of cultured intestinal
      epithelial cells on a deformable substrate, with the goal of elucidating how a
      tissue engineer might best recreate the regular array of invaginations (crypts of
      Lieberkuhn) found in the wall of the mammalian intestine. We extend the standard
      von Karman equations to incorporate inhomogeneity in the plate's mechanical
      properties and surface stresses applied to the substrate by cell proliferation.
      We determine numerically the configurations of a homogeneous plate under uniform
      cell growth, and show how tethering to an underlying elastic foundation can be
      used to promote higher-order buckled configurations. We then examine the
      independent effects of localised softening of the substrate and spatial
      patterning of cellular growth, demonstrating that (within a two-dimensional
      framework, and contrary to the predictions of one-dimensional models) growth
      patterning constitutes a more viable mechanism for control of crypt distribution
      than does material inhomogeneity. 

PMID- 24128752
TI  - Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting
      in mitochondrial depolarization and lysosomal destabilization.
AB  - Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug for the
      treatment of osteoarthritis and various rheumatic diseases. Currently, KP is
      applied topically on skin as gel to treat symptoms of pain and inflammation. We
      have studied the photomodification of KP under natural environmental conditions.
      KP generates reactive oxygen species (ROS) like 1O2 through Type-II photodynamic
      reaction. 1O2 mediated 2'-dGuO photodegradation, single and double strand
      breakage were significantly induced by photosensitized KP under sunlight/UV-R
      exposure. Significant intracellular ROS generation was measured through DCF-DA
      fluorescence. Linoleic acid photoperoxidation and role of 1O2 were substantiated
      by using specific quencher like sodium azide. KP induced cell cycle arrest in
      G2/M phase and cell death through MTT assay. We found apoptosis as the pattern of
      cell death which was confirmed through caspase-3 activation, cytochrome-c release
      from mitochondria, up-regulation of Bax protein and phosphatidylserine
      translocation. Our RT-PCR result strongly supports our view point of apoptotic
      cell death through up-regulation of p21 and pro-apoptotic Bax genes expression.
      Mitochondrial depolarization and lysosomal destabilization were also parallel to
      apoptotic process. Therefore, much attention should be paid to the topical
      application of KP and sunlight exposure in the light of skin related
      photosensitivity and cancers.

PMID- 24128753
TI  - Differences in shoot and root terpenoid profiles and plant responses to
      fertilisation in Tanacetum vulgare.
AB  - Intraspecific chemical diversity is a common phenomenon especially found in
      shoots of essential oil-accumulating plant species. Abiotic factors can influence
      the concentration of essential oils, but the effects are inconsistent and little
      is known in how far these may vary within an individual and within species
      between chemotypes. Tanacetum vulgare L. occurs in various chemotypes that differ
      in the composition of mono- and sesquiterpenoids in their shoot tissues. We
      investigated how far shoot chemotype grouping is mirrored in root terpenoid
      profiles. Furthermore, we studied whether different fertilisation amounts
      influence the plant growth and morphological traits as well as the constitutive
      terpenoid concentration of leaves and roots of three chemotypes, trans-carvyl
      acetate, beta-thujone, and camphor, to different degrees. Shoot terpenoids were
      dominated by monoterpenoids, while the roots contained mainly sesquiterpenoids.
      The clear grouping in three chemotypes based on leaf chemistry was weakly
      mirrored in the root terpenoid composition. Furthermore, the leaf C/N ratio and
      the stem height differed between chemotypes. All plants responded to increased
      nutrient availability with increased total biomass and specific leaf area but
      decreased C/N and root/shoot ratios. Leaf terpenoid concentrations decreased with
      increasing fertiliser supply, independent of chemotype. In contrast to the
      leaves, the terpenoid concentrations of the roots were unaffected by
      fertilisation. Our results demonstrate that aboveground and belowground organs
      within a species can be under different selection pressures. 

PMID- 24128754
TI  - The importance of localized culling in stabilizing chronic wasting disease
      prevalence in white-tailed deer populations.
AB  - Strategies to contain the spread of disease often are developed with incomplete
      knowledge of the possible outcomes but are intended to minimize the risks
      associated with delaying control. Culling of game species by government agencies
      is one approach to control disease in wild populations but is unpopular with
      hunters and wildlife enthusiasts, politically unpalatable, and erodes public
      support for agencies responsible for wildlife management. We addressed the
      functional differences between hunting and government culling programs for
      managing chronic wasting disease (CWD) in white-tailed deer by comparing
      prevalence over a 10-year period in Illinois and Wisconsin. When both Illinois
      and Wisconsin were actively culling from 2003 - 2007, there were no statistical
      differences between state CWD prevalence estimates. Wisconsin government culling
      concluded in 2007 and average prevalence over the next five years was 3.09 +/-
      1.13% with an average annual increase of 0.63%. During that same time period,
      Illinois continued government culling and there was no change in prevalence
      throughout Illinois. Despite its unpopularity among hunters, localized culling is
      a disease management strategy that can maintain low disease prevalence while
      minimizing impacts on recreational deer harvest.

PMID- 24128755
TI  - Transdisciplinary research for complex One Health issues: a scoping review of key
      concepts.
AB  - In order to address the complexity inherent in researching One Health (OH)
      issues, we support the concept that researchers must transcend individual
      disciplinary and non-disciplinary boundaries, and move into the realm of
      transdisciplinary (TD) research approaches. For the purposes of this paper we use
      the term OH and the concept that OH research is conducted to solve complex health
      challenges at the animal-human--human-ecosystem interface. TD goes beyond
      interdisciplinary research to engages disciplines and communities through a
      unified conceptual framework. In this scoping review we investigated key
      concepts, definitions and themes in OH and TD based on the peer reviewed
      literature. We identified nine emerging themes in TD research: (1) education, (2)
      conflict amongst disciplines, (3) effective communication, (4) shared conceptual
      framework, (5) leadership, (6) perceived power differentials, (7) community-based
      methodologies, (8) support for TD research and (9) time and effort. This review
      provides a synthesized knowledge base that describes the nature, extent of
      evidence and challenges of engaging in TD initiatives. This knowledge base
      further provides a foundation for those interested in developing improved
      strategies for TD collaborative and cross-sectoral research in OH. 

PMID- 24128756
TI  - Independent appraiser assessment of the quality, methodological rigour and
      transparency of the development of the 2008 international consensus statement on
      concussion in sport.
AB  - AIM: In recent years, considerable effort has been devoted to the development and
      revisions to an international consensus statement on concussion in sport (ICSCS).
      The aim of this study was to obtain expert views on the methodological rigour and
      transparency with which the 2008 ICSCS was developed, as a precursor to the
      development of the 2012 update. METHODS: Delegates registered for the 2012 fourth
      International Conference on Concussion in Sport, selected local concussion
      researchers not involved in any prior international consensus meetings, and all
      authors of the 2008 ICSCS published paper were invited to assess the
      methodological rigour and transparency with which the 2008 ICSCS was developed.
      The online Appraisal of Guidelines for Research and Evaluation (AGREE) II
      assessment tool, with six quality domains, was used and domain scores were
      expressed as a percentage of the maximum possible score for that domain. RESULTS:
      18 appraisers completed the online AGREE II assessment. Ten appraisers said they
      would recommend the 2008 ICSCS for use (without modification) and seven said they
      would recommend its use with some modification. The 'scope and purpose' and
      'clarity of presentation' were rated highest, both scoring 78%. The lowest
      scoring domain was 'applicability' with a score of 55%. CONCLUSIONS: The quality
      of the ICSCS is important because it is used to guide return-to-play decisions
      and the management of sport-related concussions. This appraisal of the 2008 ICSCS
      suggests that a greater focus is needed on the actual implementation of future
      ICSCS and the relationship between implementation and desired health outcomes.

PMID- 24128757
TI  - Declining incidence of surgery for Achilles tendon rupture follows publication of
      major RCTs: evidence-influenced change evident using the Finnish registry study.
AB  - OBJECTIVES: Acute Achilles tendon ruptures are common among highly active people.
      Recently published studies have provided increasing evidence to support non
      surgical treatment. This study aimed to assess the incidence trends of surgically
      treated, acute Achilles tendon ruptures. Our hypothesis, based on the recent
      literature showing no difference in functional results between surgical and non
      surgical treatment, was that the incidence of surgery would be declining.
      METHODS: We conducted a nationwide hospital register-based study. All patients 18
      years of age or older with a diagnosis of acute Achilles tendon injury, and
      treated with Achilles tendon repair from 1987 to 2011 in Finland were included in
      the study. RESULTS: During the 25-year study period in Finland, a total of 15,252
      patients received surgical treatment for an acute Achilles tendon rupture. The
      incidence of surgical treatment of acute Achilles tendon rupture in men was
      11.1/100,000 person-years in 1987 and 20.5/100,000 person-years in 2011. The
      corresponding figures in women were 2.5/100,000 person-years in 1987 and
      4.2/100,000 person-years in 2011. The highest rates occurred in 2008 in men and
      2007 in women, and since then the decrease has been 42% in men and 55% in women.
      CONCLUSIONS: During the past few years, the rate of surgically treated acute
      Achilles tendon ruptures has declined remarkably. The findings of the present
      study indicate that orthopaedic surgeons have chosen more often non-surgical
      treatment option for acute Achilles ruptures. This can be considered as an
      example, how high-quality scientific evidence can lead to a rapid change in
      clinical practice.

PMID- 24128758
TI  - Native contacts determine protein folding mechanisms in atomistic simulations.
AB  - The recent availability of long equilibrium simulations of protein folding in
      atomistic detail for more than 10 proteins allows us to identify the key
      interactions driving folding. We find that the collective fraction of native
      amino acid contacts, Q, captures remarkably well the transition states for all
      the proteins with a folding free energy barrier. Going beyond this global
      picture, we devise two different measures to quantify the importance of
      individual interresidue contacts in the folding mechanism: (i) the log-ratio of
      lifetimes of contacts during folding transition paths and in the unfolded state
      and (ii) a Bayesian measure of how predictive the formation of each contact is
      for being on a transition path. Both of these measures indicate that native, or
      near-native, contacts are important for determining mechanism, as might be
      expected. More remarkably, however, we found that for almost all the proteins,
      with the designed protein alpha3D being a notable exception, nonnative contacts
      play no significant part in determining folding mechanisms. 

PMID- 24128759
TI  - Depressed pacemaker activity of sinoatrial node myocytes contributes to the age
      dependent decline in maximum heart rate.
AB  - An inexorable decline in maximum heart rate (mHR) progressively limits human
      aerobic capacity with advancing age. This decrease in mHR results from an age
      dependent reduction in "intrinsic heart rate" (iHR), which is measured during
      autonomic blockade. The reduced iHR indicates, by definition, that pacemaker
      function of the sinoatrial node is compromised during aging. However, little is
      known about the properties of pacemaker myocytes in the aged sinoatrial node.
      Here, we show that depressed excitability of individual sinoatrial node myocytes
      (SAMs) contributes to reductions in heart rate with advancing age. We found that
      age-dependent declines in mHR and iHR in ECG recordings from mice were paralleled
      by declines in spontaneous action potential (AP) firing rates (FRs) in patch
      clamp recordings from acutely isolated SAMs. The slower FR of aged SAMs resulted
      from changes in the AP waveform that were limited to hyperpolarization of the
      maximum diastolic potential and slowing of the early part of the diastolic
      depolarization. These AP waveform changes were associated with cellular
      hypertrophy, reduced current densities for L- and T-type Ca(2+) currents and the
      "funny current" (If), and a hyperpolarizing shift in the voltage dependence of
      If. The age-dependent reduction in sinoatrial node function was not associated
      with changes in beta-adrenergic responsiveness, which was preserved during aging
      for heart rate, SAM FR, L- and T-type Ca(2+) currents, and If. Our results
      indicate that depressed excitability of individual SAMs due to altered ion
      channel activity contributes to the decline in mHR, and thus aerobic capacity,
      during normal aging. 

PMID- 24128760
TI  - Drug resistance confounding prion therapeutics.
AB  - There is not a single pharmaceutical that halts or even slows any
      neurodegenerative disease. Mounting evidence shows that prions cause many
      neurodegenerative diseases, and arguably, scrapie and Creutzfeldt-Jakob disease
      prions represent the best therapeutic targets. We report here that the previously
      identified 2-aminothiazoles IND24 and IND81 doubled the survival times of scrapie
      infected, wild-type mice. However, mice infected with Rocky Mountain Laboratory
      (RML) prions, a scrapie-derived strain, and treated with IND24 eventually
      exhibited neurological dysfunction and died. We serially passaged their brain
      homogenates in mice and cultured cells. We found that the prion strain isolated
      from IND24-treated mice, designated RML[IND24], emerged during a single passage
      in treated mice. Although RML prions infect both the N2a and CAD5 cell lines,
      RML[IND24] prions could only infect CAD5 cells. When passaged in CAD5 cells, the
      prions remained resistant to high concentrations of IND24. However, one passage
      of RML[IND24] prions in untreated mice restored susceptibility to IND24 in CAD5
      cells. Although IND24 treatment extended the lives of mice propagating different
      prion strains, including RML, another scrapie-derived prion strain ME7, and
      chronic wasting disease, it was ineffective in slowing propagation of Creutzfeldt
      Jakob disease prions in transgenic mice. Our studies demonstrate that prion
      strains can acquire resistance upon exposure to IND24 that is lost upon passage
      in mice in the absence of IND24. These data suggest that monotherapy can select
      for resistance, thus intermittent therapy with mixtures of antiprion compounds
      may be required to slow or stop neurodegeneration.

PMID- 24128761
TI  - Using protein backbone mutagenesis to dissect the link between ion occupancy and
      C-type inactivation in K+ channels.
AB  - K(+) channels distinguish K(+) from Na(+) in the selectivity filter, which
      consists of four ion-binding sites (S1-S4, extracellular to intracellular) that
      are built mainly using the carbonyl oxygens from the protein backbone. In
      addition to ionic discrimination, the selectivity filter regulates the flow of
      ions across the membrane in a gating process referred to as C-type inactivation.
      A characteristic of C-type inactivation is a dependence on the permeant ion, but
      the mechanism by which permeant ions modulate C-type inactivation is not known.
      To investigate, we used amide-to-ester substitutions in the protein backbone of
      the selectivity filter to alter ion binding at specific sites and determined the
      effects on inactivation. The amide-to-ester substitutions in the protein backbone
      were introduced using protein semisynthesis or in vivo nonsense suppression
      approaches. We show that an ester substitution at the S1 site in the KcsA channel
      does not affect inactivation whereas ester substitutions at the S2 and S3 sites
      dramatically reduce inactivation. We determined the structure of the KcsA S2
      ester mutant and found that the ester substitution eliminates K(+) binding at the
      S2 site. We also show that an ester substitution at the S2 site in the KvAP
      channel has a similar effect of slowing inactivation. Our results link C-type
      inactivation to ion occupancy at the S2 site. Furthermore, they suggest that the
      differences in inactivation of K(+) channels in K(+) compared with Rb(+) are due
      to different ion occupancies at the S2 site. 

PMID- 24128762
TI  - Ca2+ ionophore A23187 can make mouse spermatozoa capable of fertilizing in vitro
      without activation of cAMP-dependent phosphorylation pathways.
AB  - Ca(2+) ionophore A23187 is known to induce the acrosome reaction of mammalian
      spermatozoa, but it also quickly immobilizes them. Although mouse spermatozoa
      were immobilized by this ionophore, they initiated vigorous motility
      (hyperactivation) soon after this reagent was washed away by centrifugation.
      About half of live spermatozoa were acrosome-reacted at the end of 10 min of
      ionophore treatment; fertilization of cumulus-intact oocytes began as soon as
      spermatozoa recovered their motility and before the increase in protein tyrosine
      phosphorylation, which started 30-45 min after washing out the ionophore. When
      spermatozoa were treated with A23187, more than 95% of oocytes were fertilized in
      the constant presence of the protein kinase A inhibitor, H89. Ionophore-treated
      spermatozoa also fertilized 80% of oocytes, even in the absence of HCO3(-), a
      component essential for cAMP synthesis under normal in vitro conditions. Under
      these conditions, fertilized oocytes developed into normal offspring. These data
      indicate that mouse spermatozoa treated with ionophore are able to fertilize
      without activation of the cAMP/PKA signaling pathway. Furthermore, they suggest
      that the cAMP/PKA pathway is upstream of an intracellular Ca(2+) increase
      required for the acrosome reaction and hyperactivation of spermatozoa under
      normal in vitro conditions. 

PMID- 24128763
TI  - Multiplatform single-sample estimates of transcriptional activation.
AB  - Over the past two decades, many biotechnology platforms have been developed for
      high-throughput gene expression profiling. However, because each platform is
      subject to technology-specific biases and produces distinct raw-data
      distributions, researchers have experienced difficulty in integrating data across
      platforms. Data integration is crucial to data-generating consortiums,
      researchers transitioning to newer profiling technologies, and individuals
      seeking to aggregate data across experiments. We address this need with our
      Universal exPression Code (UPC) approach, which corrects for platform-specific
      background noise using models that account for the genomic base composition and
      length of target regions; this approach also uses a mixture model to estimate
      whether a gene is active in a particular profiling sample. The latter produces
      standardized UPC values on a zero-to-one scale, so that they can be interpreted
      consistently, irrespective of profiling technology, thus enabling downstream
      analysis pipelines to be developed in a platform-agnostic manner. The UPC method
      can be applied to one- and two-channel expression microarrays and to next
      generation sequencing data (RNA sequencing). Furthermore, UPCs are derived using
      information from within a given sample only--no ancillary samples are required at
      processing time. Thus, UPCs are suitable for personalized-medicine workflows
      where samples must be processed individually rather than in batches. In a variety
      of analyses and comparisons, UPCs perform comparably to other methods designed
      specifically for microarrays or RNA sequencing in most settings. Software for
      calculating UPCs is freely available at
      www.bioconductor.org/packages/release/bioc/html/SCAN.UPC.html.

PMID- 24128764
TI  - Comparing a simple theoretical model for protein folding with all-atom molecular
      dynamics simulations.
AB  - Advances in computing have enabled microsecond all-atom molecular dynamics
      trajectories of protein folding that can be used to compare with and test
      critical assumptions of theoretical models. We show that recent simulations by
      the Shaw group (10, 11, 14, 15) are consistent with a key assumption of an Ising
      like theoretical model that native structure grows in only a few regions of the
      amino acid sequence as folding progresses. The distribution of mechanisms
      predicted by simulating the master equation of this native-centric model for the
      benchmark villin subdomain, with only two adjustable thermodynamic parameters and
      one temperature-dependent kinetic parameter, is remarkably similar to the
      distribution in the molecular dynamics trajectories. 

PMID- 24128765
TI  - beta diversity contributes to ecosystem processes more than by simply summing the
      parts.

PMID- 24128766
TI  - A novel computer algorithm allows for volumetric and cross-sectional area
      analysis of indirect decompression following transpsoas lumbar arthrodesis
      despite variations in MRI technique.
AB  - Many patients present for neurosurgical spine evaluation with MRI studies
      conducted at facilities outside of the treating medical center. These images
      often vary widely in technique, for example, variation in slice thickness, number
      of slices, and gantry angle. While these images may be sufficient in conjunction
      with a physical exam to make surgical evaluations, we have found they are often
      incapable of being used for objective post-operative volumetric comparisons. In
      order to overcome this, we created a computer program that compensates for these
      variations in MRI technique. For this study, we examined patients who had
      undergone outside MRI pre-operatively and were deemed appropriate for a lateral
      retroperitoneal transpsoas lumbar interbody arthrodesis procedure. Volumetric
      analysis was performed on sagittal and axial T2-weighted pre- and post-operative
      MRI. The percentage change of central canal volume and foraminal area was
      calculated for each level. The authors identified five levels with MRI sufficient
      for volumetric analysis and eight levels (16 foramina) sufficient for foraminal
      cross-sectional analysis. Through use of our computer algorithm, average central
      canal volume and foraminal cross-sectional area was calculated to increase by
      32.8% and 67.6% respectively following the procedure. These results are
      consistent with previous study findings and support the idea that restoration of
      the anterior column via a lateral approach can result in significant indirect
      decompression of the neural elements. Additionally, the novel algorithm created
      and used for this study suggests that it can achieve quick measurement and
      comparison of MRI studies despite variations in pre- and post-operative
      technique. 

PMID- 24128767
TI  - Association of the A1298C polymorphism in MTHFR gene with ischemic stroke.
AB  - A meta-analysis was performed to assess the association between the
      methylenetetrahydrofolate reductase (MTHFR) A1298C genetic polymorphism and
      ischemic stroke. A comprehensive search was conducted to identify all case
      control or cohort studies. The fixed or random effect pooled measure was selected
      based on the homogeneity between studies, as assessed by I(2). Meta-regression
      was used to explore the potential sources of between-study heterogeneity.
      Publication bias was estimated using Egger's linear regression test. Thirteen
      case-control studies corresponded to the inclusion criteria comprising 2133
      patients and 2572 controls which were included in the present meta-analysis.
      After excluding articles that deviated from Hardy-Weinberg equilibrium in
      controls and the key contributors to between-study heterogeneity, significant
      associations between MTHFR A1298C genetic polymorphism and risk of ischemic
      stroke were observed in dominant (odds ratio [OR] 1.227, 95% confidence interval
      [CI] 1.062-1.416) and codominant (OR 1.138, 95% CI 1.007-1.286) inheritance
      models. Moreover, in the subgroup analysis based on region (Asia and Europe),
      significant associations were observed in most genetic models in Asia but not in
      Europe. This meta-analysis suggests that MTHFR A1298C genetic polymorphism is
      associated with increased risk of ischemic stroke, and the C allele may be an
      important risk factor for ischemic stroke. 

PMID- 24128768
TI  - The SILK flow diverter in the treatment of intracranial aneurysms.
AB  - The SILK flow diverter (SFD; Balt Extrusion, Montmorency, France) is a flow
      diverting stent used in the endovascular treatment of intracranial aneurysms. It
      works on the principle of redirecting flow away from the aneurysm sac, leading to
      occlusion over time. We present a systematic review on the clinical outcomes and
      complications of the SFD. A literature search for English language articles were
      conducted on PubMed, Medline and EMBASE for articles on the treatment of
      intracranial aneurysms with the SILK flow diverter. The inclusion criteria were
      n>10, use of SFD only, data on complications and aneurysm occlusion rate (AOR).
      Eight studies with 285 patients and 317 intracranial aneurysms were included. The
      mean age was 52.7 years and nearly 80% were women. In terms of angiographic
      distribution, 86.8% of aneurysms were located in the anterior circulation and
      13.2% in the posterior circulation. As for the aneurysm size, 37.9% were classed
      as small, 44.4% as large and 17.7% as giant. Ischemic complications and parent
      artery occlusion each occurred in 10% of patients. Aneurysm rupture rate was
      3.5%, while the cumulative mortality was 4.9%. The main outcome measure, 12 month
      AOR, was 81.8% with complete occlusion in 216 out of 264 aneurysms. Use of flow
      diverters for the treatment of intracranial aneurysm with complex morphologies
      has gained in popularity over the last few years. Our review suggests that SFD
      achieves comparable AOR to its contemporary, the Pipeline Embolization Device
      (ev3 Endovascular, Plymouth, MN, USA) but has a higher rate of higher rate of
      ischemic complications, aneurysm rupture and mortality.

PMID- 24128769
TI  - Holospinal epidural abscess.
AB  - Holospinal epidural abscess (HEA) is an extremely rare condition in which spinal
      epidural abscesses extend from the cervical to the sacral spine. We report two
      patients who presented with myelopathy secondary to HEA. Both patients underwent
      urgent surgical decompression and abscess drainage, and had significant
      improvement in neurological function. We discuss the surgical management
      strategies and briefly review the literature regarding HEA. 

PMID- 24128770
TI  - Stenting of symptomatic vertebral artery ostium stenosis with self-expanding
      stents.
AB  - Symptomatic vertebral arterial stenosis carries a stroke risk of 30% at 5 years.
      The efficacy of stenting with balloon-expandable stents remains questionable due
      to a high long-term restenosis rate. This study aimed to investigate the
      feasibility and efficacy of using self-expanding stents to treat symptomatic
      vertebral artery ostium (VAO) stenosis in selected patients. Clinical and
      angiographic results were retrospectively reviewed in patients with symptomatic
      VAO stenosis who underwent stenting with self-expanding stents between June 2008
      and December 2011. In total, 32 patients were included. Self-expanding stents (25
      tapered and seven non-tapered) were deployed with a modified technique of
      deploying the stents from the V1 segment to the proximal subclavian artery. The
      mean degree of stenosis before and after stenting declined from 76.4% to 11.4%.
      No peri-procedural complications occurred. During the mean clinical follow-up of
      18.3 months, no vertebrobasilar stroke, transient ischemic attack or death
      occurred. During the mean angiographic follow-up of 12.5 months, asymptomatic
      restenosis occurred in one (3.1%) patient 6 months after the procedure. No stent
      fracture occurred. The involved subclavian artery was patent and no clinically
      apparent events occurred in the dependent upper extremity. Stenting with self
      expanding stents for symptomatic VAO stenosis is technically feasible and safe,
      with reduced restenosis and stent fracture rates in selected patients. Long-term
      investigations are warranted to validate its performance.

PMID- 24128771
TI  - Childhood Guillain-Barre syndrome subtypes in northern India.
AB  - This prospective cross-sectional study was conducted at a tertiary care research
      centre in North India to describe the frequency and clinical characteristics of
      subtypes of childhood Guillain-Barre syndrome. Among the 68 children enrolled, 65
      were finally diagnosed with Guillain-Barre syndrome (median age, 60 months); 45
      (69%) were boys. The most common subtype was acute motor axonal neuropathy in 27
      patients (41.5%, 95% confidence interval [CI] 29-54), followed by acute
      inflammatory demyelinating polyneuropathy in 15 (23%, 95% CI 13.5-35), and acute
      motor sensory axonal neuropathy in three (4.6%, 95% CI 1-13). Twelve patients
      (18.5%, 95% CI 10-30) had inexcitable nerves, and eight (12.4%, 95% CI 5.5-23)
      were unclassifiable. Those with acute inflammatory demyelinating polyneuropathy
      were more likely to have had a preceding upper respiratory tract infection. The
      acute motor axonal neuropathy subtype peaked in incidence during the winter and
      monsoon months.

PMID- 24128772
TI  - Orbital venous congestion: rare manifestation of an intracranial arteriovenous
      malformation.
AB  - Intracranial arteriovenous malformations (AVM) are uncommon vascular lesions
      which typically present with hemorrhage or, in the case of unruptured lesions,
      with seizure, headache, or focal neurological deficit. The importance of the
      venous drainage pattern in AVM natural history and treatment outcomes is well
      documented. It is exceptionally rare for an AVM to drain into the orbital venous
      system. We present a 42-year-old man with a large, complex AVM of the midbrain,
      basal ganglia, and thalamus which partially drained into the superior ophthalmic
      vein. The patient was referred for treatment with radiosurgery. The resolution of
      orbital venous congestion symptoms accompanied AVM obliteration. An attempt to
      relieve orbital venous congestion by endovascular obliteration or surgical
      ligation without successful and complete cure of the AVM will most likely
      destabilize the nidus and predispose it to rupture. Serial ophthalmologic
      monitoring by an experienced neuro-ophthalmologist is crucial to monitoring the
      ophthalmologic effects of AVM progression and treatment. 

PMID- 24128773
TI  - Incidence and risk factors associated with in-hospital venous thromboembolism
      after aneurysmal subarachnoid hemorrhage.
AB  - Our purpose was to determine the incidence and risk factors associated with in
      hospital venous thromboembolism (VTE) in patients with aneurysmal subarachnoid
      hemorrhage (aSAH). The Nationwide Inpatient Sample database was queried from 2002
      to 2010 for hospital admissions for subarachnoid hemorrhage or intracerebral
      hemorrhage and either aneurysm clipping or coiling. Exclusion criteria were age
      <18, arteriovenous malformation/fistula diagnosis or repair, or radiosurgery.
      Primary outcome was VTE (deep vein thrombosis [DVT] or pulmonary embolus [PE]).
      Multivariate logistic regression was used to assess association between risk
      factors and VTE. Secondary outcomes were in-hospital mortality, discharge
      disposition, length of stay and hospital charges. A total of 15,968 hospital
      admissions were included. Overall rates of VTE (DVT or PE), DVT, and PE were
      4.4%, 3.5%, and 1.2%, respectively. On multivariate analysis, the following
      factors were associated with increased VTE risk: increasing age, black race, male
      sex, teaching hospital, congestive heart failure, coagulopathy, neurologic
      disorders, paralysis, fluid and electrolyte disorders, obesity, and weight loss.
      Patients that underwent clipping versus coiling had similar VTE rates. VTE was
      associated with pulmonary/cardiac complication (odds ratio [OR] 2.8), infectious
      complication (OR 2.8), ventriculostomy (OR 1.8), and vasospasm (OR 1.3). Patients
      with VTE experienced increased non-routine discharge (OR 3.3), and had nearly
      double the mean length of stay (p<0.001) and total inflation-adjusted hospital
      charges (p<0.001). To our knowledge, this is the largest study evaluating the
      incidence and risk factors associated with the development of VTE after aSAH. The
      presence of one or more of these factors may necessitate more aggressive VTE
      prophylaxis. 

PMID- 24128774
TI  - Worker productivity outcome measures: OMERACT filter evidence and agenda for
      future research.
AB  - The objective of the Outcome Measures in Rheumatology (OMERACT) Worker
      Productivity working group is to identify worker productivity outcome measures
      that meet the requirements of the OMERACT filter. At the OMERACT 11 Workshop, we
      focused on the at-work limitations/productivity component of worker productivity
      (i.e., presenteeism) - an area with diverse conceptualization and instrumentation
      approaches. Various approaches to quantify at-work limitations/productivity
      (e.g., single-item global and multi-item measures) were examined, and available
      evidence pertaining to OMERACT truth, discrimination, and feasibility were
      presented to conference participants. Four candidate global measures of
      presenteeism were put forth for a plenary vote to determine whether current
      evidence meets the OMERACT filter requirements. Presenteeism globals from the
      Work Productivity and Activity Impairment Questionnaire (72% support) and
      Rheumatoid Arthritis-specific Work Productivity Survey (71% support) were
      endorsed by conference participants; however, neither the presenteeism global
      item from the Health and Work Performance Questionnaire nor the Quantity and
      Quality method achieved the level of support required for endorsement at the
      present time. The plenary was also asked whether the central item from the Work
      Ability Index should also be considered as a candidate measure for potential
      endorsement in the future. Of participants at the plenary, 70% supported this
      presenteeism global measure. Progress was also made in other areas through
      discussions at individual breakout sessions. Topics examined include the merits
      of various multi-item measures of at-work limitations/productivity,
      methodological issues related to interpretability of outcome scores, and
      approaches to appraise and classify contextual factors of worker productivity.
      Feedback gathered from conference participants will inform the future research
      agenda of the working group. 

PMID- 24128775
TI  - Including health equity considerations in development of instruments for
      rheumatology research: an introduction to a novel OMERACT paradigm.
AB  - The Outcome Measures in Rheumatology (OMERACT) Equity Special Interest Group
      (SIG) was established in 2008 to create a preliminary core set of outcome
      measures for clinical trials that can assess equity gaps in healthcare and the
      effectiveness of interventions to close or narrow gaps between advantaged and
      disadvantaged populations with musculoskeletal (MSK) conditions. At the OMERACT
      11 meeting in 2012, the Equity SIG workshop focused on health assessment scales
      and their applicability for disadvantaged patients with MSK conditions. The
      intent was to determine whether the items and domains in 2 common questionnaires,
      the Health Assessment Questionnaire and the Medical Outcome Study Short Form-36
      Survey, are appropriate for the activities and life experiences of certain
      disadvantaged populations, and whether completion of any of the scales would
      present a challenge to disadvantaged persons. To generate discussion, we
      considered the reading level of items in these questionnaires and whether they
      would be accessible to people with different levels of literacy. The group
      concluded that the choice of measurement instrument may contribute to "outcome
      measure-generated inequalities" because disadvantaged groups might have
      difficulty understanding some of the questions. The future work of the Equity SIG
      will explore the appropriateness of different measurement scales as they relate
      to inequities in arthritis as well as the risk of exacerbating disadvantages for
      patients with low literacy. 

PMID- 24128776
TI  - Myocardial perfusion imaging in Takayasu arteritis.
AB  - OBJECTIVE: Myocardial perfusion defects using scintigraphy have been frequently
      observed in patients with Takayasu arteritis (TA) without coronary stenosis. The
      aim of our study was to evaluate coronary microcirculation in TA using thallium
      201 (201Tl) myocardial scintigraphy and dipyridamole (DPM) as vasodilator agent.
      METHODS: Twenty-five consecutive patients with TA were prospectively recruited.
      They were asymptomatic for cardiac issues and examined using 201Tl myocardial
      scintigraphy at rest and after coronary artery vasodilation with intravenous DPM.
      Factors associated with improvement in myocardial perfusion after DPM were
      identified in patients with TA. RESULTS: Among 25 patients with TA, 21 (84%) had
      201Tl myocardial perfusion defects and 4 (16%) had normal resting myocardial
      perfusion. Using a 17-segments model for quantitative image analysis, DPM
      significantly improved resting 201Tl myocardial perfusion in 14 patients (61%)
      versus 9 patients without improvement (39%). We were able to examine coronary
      artery stenoses in 11 patients, including 10 patients with thallium perfusion
      defects, and significant coronary artery stenoses were present in only 2 patients
      (18.2%). No significant difference was found in traditional cardiovascular risk
      factors between TA patients with or without improvement of myocardial perfusion
      after DPM. The absence of improvement in myocardial perfusion after DPM tended to
      be closely associated with specific features and prognostic factors of TA, such
      as aortic regurgitation at diagnosis, renovascular hypertension, longer duration
      of TA disease, and male sex. CONCLUSION: We found the significantly high
      prevalence of myocardial perfusion defects mostly improved after vasodilation
      with DPM, which may indicate the major role of microcirculatory dysfunction in
      myocardial ischemia in TA.

PMID- 24128777
TI  - What has been the effect on trial outcome assessments of a decade of patient
      participation in OMERACT?
AB  - OBJECTIVE: Since 2002, 58 patients have participated as collaborating partners in
      6 Outcome Measures in Rheumatology (OMERACT) conferences. Little is known about
      how they engage with researchers and how they have influenced conference
      outcomes. METHODS: A responsive evaluation was carried out, including a thematic
      document analysis of conference proceedings and gray literature, participant
      observation, and 38 interviews with patients and professionals representing
      research, industry, and regulators. Interview transcripts were subjected to an
      inductive content analysis. RESULTS: The role of patients has evolved from a
      single focus group in 2002 to full integration in all parts of the conference in
      2012. Longterm engagement has made a significant change in the scope and conduct
      of rheumatology research. It has enriched the research agenda by identifying
      previously neglected outcome domains such as fatigue, sleep disturbances, and
      flares, and it has contributed to more patient-relevant outcomes in clinical
      trials. Facilitating factors have been a strong commitment of the leadership,
      adequate selection procedure, inclusive conference design, interactive and
      encouraging moderation style, and self-organized support. The intensity of the
      program and doubts regarding the representativeness of the patient group were
      still seen as challenges for the future. CONCLUSION: Making patient participation
      an integral part of the vision and procedures of OMERACT has significantly
      contributed to the success of OMERACT. It has changed the perceptions and beliefs
      of many participants. Full use of patients' experiential knowledge before and
      during the conference is still challenging.

PMID- 24128778
TI  - Nailfold capillaroscopy for prediction of novel future severe organ involvement
      in systemic sclerosis.
AB  - OBJECTIVE: Assessment of associations of nailfold videocapillaroscopy (NVC)
      scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel
      future severe clinical involvement in 2 independent cohorts. METHODS: Sixty-six
      consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline.
      Images were blindly assessed and classified into normal, early, active, or late
      NVC pattern. Clinical evaluation was performed for 9 organ systems (general,
      peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart,
      and kidney) according to the Medsger disease severity scale (DSS) at baseline and
      in the future (18-24 months of followup). Severe clinical involvement was defined
      as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous
      NVC predictor variable) was performed. RESULTS: The OR to develop novel future
      severe organ involvement was stronger according to more severe NVC patterns and
      similar in both cohorts. In simple logistic regression analysis the OR in the
      Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36
      4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern,
      and 10.14/12.63 for the late pattern versus the normal pattern. In multiple
      logistic regression analysis, adjusting for disease duration, subset, and
      vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI
      1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active
      pattern, and 26.69/6.66 for the late pattern versus the normal pattern.
      CONCLUSION: Capillaroscopy may be predictive of novel future severe organ
      involvement in SSc, as attested by 2 independent cohorts.

PMID- 24128779
TI  - Assessment of coronary risk based on cumulative exposure to lipids in systemic
      lupus erythematosus.
AB  - OBJECTIVE: To quantify the independent role of each of low-density lipoprotein
      cholesterol (LDL-C), total cholesterol:high-density lipoprotein cholesterol ratio
      (TC:HDL-C), triglyceride (TG) level, and HDL-C as a marker of coronary risk in
      systemic lupus erythematosus (SLE). METHODS: Patients with lipid measurements
      taken before a coronary event (or last clinic visit) were included. Mean and time
      adjusted mean (TAM) levels were calculated for each lipid variable in each
      patient. Time-dependent proportional hazards regression models were used to
      quantify the risk of coronary event [myocardial infarction (MI) or angina], after
      adjustment for age. RESULTS: Among 384 patients, over a mean (SD) followup of
      3.81 (2.58) years, there were 21 "first" coronary events (6 MI, 15 angina). Mean
      and TAM LDL-C (HR 1.83, 95% CI 1.19-2.81, p = 0.006), TC:HDL ratio (HR 1.43, 95%
      CI 1.02-2.00, p = 0.04), and TG (HR 2.11, 95% CI 1.32-3.39, p = 0.0019) were
      predictive of coronary event at subsequent visits. In contingency table analysis,
      TAM LDL-C cutpoint of 2.0 mmol/l had a sensitivity and negative predictive value
      for coronary event of 85.7% (95% CI 63.7-97.0) and 93.9% (95% CI 83.1-98.7),
      respectively. However, at this cutpoint the specificity was only 12.7% (95% CI
      9.4-16.5). CONCLUSION: This study links LDL-C, TC:HDL-C ratio, and TG to coronary
      risk in patients with SLE and quantifies the magnitude of this risk. SLE-specific
      risk assessment levels for lipids may be selected to optimize positive or
      negative predictive values.

PMID- 24128780
TI  - Patients with antineutrophil cytoplasmic antibodies associated vasculitis in
      remission are hypercoagulable.
AB  - OBJECTIVES: The risk of venous thromboembolism (VTE) is increased in patients
      with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides (AAV)
      as compared to healthy subjects. The mechanisms underlying this increased
      occurrence of VTE are not completely understood. We hypothesize that AAV patients
      in remission are more procoagulant than healthy controls. METHODS: Patients with
      AAV in remission and no VTE for the last 6 months were included. Patients with
      severe renal impairment (serum creatinine > 250 MUmol/l) were excluded. Age and
      sex matched healthy controls were included. The endogenous thrombin potential
      (ETP) was determined together with hemostatic variables: fibrinogen, D-dimers,
      factor VIII (FVIII), tissue factor pathway inhibitor (TFPI), protein C, and free
      protein S. RESULTS: Thirty-one patients were included. In 27 patients not taking
      anticoagulants, ETP was measured and found to be elevated: 137.1% as compared to
      a median of 90.0% for healthy controls (p < 0.01). Fibrinogen and D-dimer levels
      were not elevated in patients (median 3.5 g/l and 279 MUg/l, respectively). FVIII
      and TFPI levels were also significantly increased in patients as compared to
      healthy controls (159% vs 137%; 122.5% vs 101%, respectively), whereas protein C
      and free protein S levels were not elevated (126.5% vs 118.6% and 124.6% vs
      118.3%, respectively). CONCLUSION: Patients with AAV in remission are more
      procoagulant than healthy controls, as indicated by an increased ETP. The
      increased FVIII level measured in these patients suggests persistence of
      endothelial activation and/or dysfunction. This endothelial dysfunction may cause
      a continuous low-grade procoagulant state.

PMID- 24128781
TI  - A systematic literature review on the application of Rasch analysis in
      musculoskeletal disease -- a special interest group report of OMERACT 11.
AB  - OBJECTIVE: The Rasch measurement model provides robust analysis of the internal
      construct validity of outcome measures. We reviewed the application of Rasch
      analysis in musculoskeletal medicine as part of the work leading to discussion in
      a Special Interest Group in Rasch Analysis at Outcome Measures in Rheumatology
      11. METHODS: A systematic literature review of SCOPUS and MEDLINE was performed
      (January 1, 1985, to February 29, 2012. Original research reports in English
      using "Rasch" or "Item Response Theory" in musculoskeletal diseases were assessed
      by 2 independent reviewers. The topics of focus and analysis methodology details
      were recorded. RESULTS: Of 212 articles reviewed, 114 were included. The number
      of publications rose from 1 in 1991-1992 to 23 in 2011-February 2012. Disease
      areas included rheumatoid arthritis (28%), osteoarthritis (16.6%), and general
      musculoskeletal disorders (43%). Sixty-six reports (57.9%) evaluated psychometric
      properties of existing scales and 35 (30.7%) involved development of new scales.
      Nine articles (7.9%) were on methodology illustration. Four articles were on item
      banking and computer adaptive testing. A majority of the articles reported fit
      statistics, while the basic Rasch model assumption (i.e., unidimensionality) was
      examined in only 57.2% of the articles. An improvement in reporting qualities
      with Rasch articles was noted over time. In addition, only 11.4% of the articles
      provided a transformation table for interval scale measurement in clinical
      practice. CONCLUSION: The Rasch model has been increasingly used in rheumatology
      over the last 2 decades in a wide range of applications. The majority of the
      articles demonstrated reasonable quality of reporting. Improvements in quality of
      reporting over time were revealed.

PMID- 24128783
TI  - Why do depressed individuals have difficulties in their parenting role?
AB  - Although existing research has shown that depression in parents has a negative
      effect on parent-child interactions, the mechanisms underpinning impaired
      parenting are still unknown. In this editorial, we review core difficulties that
      have been noted in depressed individuals including reduced positive and increased
      negative affect, poor emotion regulation, executive function deficits, reduced
      motivation and rumination, and discuss how each of these can alter parenting. We
      suggest that these causal processes are inter-related and can interact with one
      another in affecting parenting. We conclude that an improved understanding of
      these processes will have implications for the development of more specific and
      potentially more effective treatments that have the potential to break the
      intergenerational transmission of psychopathology. 

PMID- 24128782
TI  - Familial Mediterranean fever (FMF) with proteinuria: clinical features,
      histology, predictors, and prognosis in a cohort of 25 patients.
AB  - OBJECTIVE: Reactive (AA) amyloidosis may complicate familial Mediterranean fever
      (FMF), the prototype of autoinflammatory diseases. Thus, proteinuria in FMF is
      commonly viewed as resulting from amyloidosis, and kidney biopsy is deemed
      superfluous. However, nephropathy other than amyloidosis has been described in
      FMF, but its rate and distinctive characteristics are unknown. Our aim was to
      determine the rate and underlying pathology of FMF-related nonamyloidotic
      proteinuria and compare its clinical course, demographic, and genetic features to
      those of FMF-amyloid nephropathy. METHODS: This study is a retrospective analysis
      of data from patients with FMF undergoing kidney biopsy for proteinuria above 0.5
      g/24 h, over 10 years (2001-2011). Clinical, laboratory, genetic, and pathology
      data were abstracted from patient files. Biopsies were viewed by an experienced
      pathologist, as necessary. RESULTS: Of the 25 patients referred for kidney
      biopsy, only 15 (60%) were diagnosed with amyloid kidney disease (AKD), and 10
      were diagnosed with another nephropathy. The AKD and nonamyloid kidney disease
      (NAKD) groups were comparable on most variables, but showed distinct
      characteristics with regard to the degree of proteinuria (6.45 +/- 4.3 g vs 2.14
      +/- 1.6 g, p = 0.006), rate of severe FMF (14 vs 5 patients, p = 0.022), and rate
      of development of end stage renal disease (73.3% vs 20%, p = 0.015),
      respectively. CONCLUSION: NAKD is common in FMF and, compared to amyloidosis, it
      is featured with milder course and better prognosis. Contrary to common practice,
      it is highly recommended to obtain a kidney biopsy from patients with FMF and
      proteinuria more than 0.5 g/24 h.

PMID- 24128784
TI  - Nursing perception of the impact of automated dispensing cabinets on patient
      safety and ergonomics in a teaching health care center.
AB  - PURPOSE: To evaluate how nursing staff felt about the impact of automated
      dispensing cabinets (ADCs) on the safe delivery of health care and workplace
      ergonomics. To identify the main issues involved in the use of this technology
      and to describe the corrective measures implemented. METHODS: Cross-sectional
      descriptive study with quantitative and qualitative components. A questionnaire
      that consisted of 33 statements about ADC was distributed from May 24 to June 3,
      2011. RESULTS: A total of 172 (46%) of 375 nurses completed the questionnaire.
      Nursing staff considered the introduction of ADC made their work easier (level of
      agreement of 90%), helped to safely provide patients with care (91%), and helped
      to reduce medication incidents/accidents (81%). Nursing staff was particularly
      satisfied by the narcotic drugs management with the ADCs. Nursing staff were not
      satisfied with the additional delays in the preparation and administration of a
      medication dose and the inability to prevent a medication from being administered
      when stopped on the medication administration record (48%). CONCLUSION: The
      nursing staff members were satisfied with the use of ADC and believed it made
      their work easier, promoted safe patient care, and were perceived to reduce
      medication incidents/accidents.

PMID- 24128785
TI  - Pilot Study on the Impact of Evidence-Based Data on Oncology Pharmacists'
      Perceptions.
AB  - OBJECTIVES: The main objective was to evaluate whether the level of agreement of
      oncology hospital pharmacists with statements on their impact is influenced by
      the presence or absence of evidence-based data. The secondary objective was to
      evaluate the relative importance of evidence-based data among factors that may
      have contributed to oncology pharmacy practice evolution. METHODS: Oncology
      pharmacists' answered a Web questionnaire to measure their level of agreement
      with statements regarding their impact. Respondents answered the questionnaire
      before (pre) and after (post) being informed whether supporting evidence was
      available for each statement. Respondents were also asked to rank all of the
      factors in order of their perceived contribution to oncology pharmacy practice
      evolution. RESULTS: A total of 64 questionnaires were obtained. Respondents
      reported a high level of agreement with statements regarding their impact on
      oncology pharmacy practice (mean agreement of 95.9% pre vs 93.8% post). A
      statistically significant diminution in the level of agreement was observed for 3
      statements after respondents were informed that no supporting evidence was
      available for these statements. Respondents assigned a high importance to factors
      related to the perception of positive outcomes of pharmaceutical activities on
      patient safety, health care costs, and clinical results but a low importance to
      the use of evidence-based data.

PMID- 24128786
TI  - Pharmacists' Roles in Post-September 11th Disasters: A Content Analysis of
      Pharmacy Literature.
AB  - PURPOSE: To characterize the roles pharmacists have assumed in disasters and
      clarify the types of roles and disasters that may be less well-documented in the
      pharmacy literature. METHODS: This research examines how balanced or equally
      proportioned role categories are in the pharmacy literature, whether pharmacy
      journals differ in the proportion of role categories reported, and whether
      journals significantly differ in the proportion of reported chemical, biological,
      radiological, nuclear (CBRN), and natural disasters. Data coding was performed
      solely by the lead author using Concordance (Harvard University, Cambridge,
      Massachusetts), a Web-based content analysis software, and Minitab((r)) (version
      15; Minitab, Inc; State College, Pennsylvania) for descriptive and inferential
      statistical analysis. Pharmacy journals publishing at least 2 articles about
      pharmacist disaster roles from September 11, 2001 to September 30, 2011 were used
      in the study and were available electronically. RESULTS: Chi-square analyses
      reveal significant differences in the weighted counts of roles, roles categorized
      by journal, and CBRN disasters categorized by journal. CONCLUSIONS: Data suggest
      that pharmacists may be prepared to respond to hurricanes and biological and
      chemical disasters in pharmaceutical supply and patient management roles. Future
      research should highlight efforts to prepare health systems for the effects of
      nuclear, radiological, and chemical disasters.

PMID- 24128787
TI  - Impact of phosphodiesterase type 5 inhibitor treatment on the rates of sexually
      transmitted diseases in a Veterans Affairs Medical Center patient population.
AB  - OBJECTIVE: The objective of this study was to investigate whether the rates of
      sexually transmitted diseases (STDs) are higher in a veteran population
      prescribed phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction
      compared to individuals not prescribed these medications. METHODS: This
      retrospective cohort study included male veterans who filled at least 1
      prescription for a PDE5 inhibitor at a Veterans Affairs Medical Center (VAMC)
      between January 1, 2007, and December 31, 2009. A comparator cohort of male
      veterans was matched for age and marital status. RESULTS: A total of 10 154
      subjects were evaluated. The number of unique subjects with confirmed STDs within
      the study period was not significantly different between the PDE5 inhibitor
      cohort and the comparator cohort (n = 8 vs 10, P = .638) nor was there a
      significant difference in the total number of STDs acquired (n = 8 vs 13, P =
      .267). Characteristics of subjects who contracted an STD included younger age,
      African American race, and single marital status. CONCLUSIONS: This study
      demonstrated that the use of a PDE5 inhibitor in this VAMC patient population was
      not associated with an increase in the incidence of STDs. Individuals who
      contracted a new STD tended to be younger, not married, and African American.

PMID- 24128788
TI  - Recombinant adenovirus snake venom cystatin inhibits the growth, invasion, and
      metastasis of B16F10 cells in vitro and in vivo.
AB  - Previous studies have shown that transfection of the snake venom cystatin (sv
      cystatin) gene can inhibit the invasion and metastasis of tumor cells. The aim of
      this study was to investigate the pharmaceutical applications of sv-cystatin in
      melanoma gene therapy. We constructed a recombinant adenovirus carrying sv
      cystatin (Ad/sv-cystatin) and a control virus (Ad/null). Matrigel assays were
      used to assess melanoma cell migration and invasiveness in vitro. The
      antimelanoma effects of Ad/sv-cystatin were assessed in a syngeneic mouse model
      with an experimental lung colonization assay. Ad/sv-cystatin significantly
      inhibited the invasion and growth of B16F10 cells in vitro compared with control
      and Ad/null. Ad/sv-cystatin significantly inhibited experimental lung
      colonization in C57BL/6 mice as compared with that in control (P<0.001) and
      Ad/null-treated mice (P<0.001), with an inhibition rate of 51 and 46%,
      respectively. Ad/sv-cystatin slowed the increase in lung weight in C57BL/6 mice
      as compared with that in control mice (P<0.001) and Ad/null-treated mice
      (P<0.001), with an inhibition rate of 40 and 35%, respectively. Our results
      indicate that Ad/sv-cystatin suppresses mouse melanoma invasion, metastasis, and
      growth in vitro and in vivo. Our findings provide support for the further
      examination of the pharmaceutical applications of Ad/sv-cystatin. 

PMID- 24128789
TI  - High expression of glycolytic and pigment proteins is associated with worse
      clinical outcome in stage III melanoma.
AB  - There are insufficient numbers of prognostic factors available for prediction of
      clinical outcome in patients with stage III malignant cutaneous melanoma, even
      when known adverse pathological risk factors, such as macrometastasis, number of
      lymph node metastases, and ulceration are taken into consideration. The aim of
      this study was therefore to identify additional prognostic factors to better
      predict patients with a high risk of relapse, thus enabling us to better
      determine the need for adjuvant treatment in stage III disease. An RNA
      oligonucleotide microarray study was performed on first regional lymph node
      metastases in 42 patients with stage III melanoma: 23 patients with short-term
      survival (<= 13 months) and 19 with long-term survival (>= 60 months), to
      identify genes associated with clinical outcome. Candidate genes were validated
      by real-time PCR and immunohistochemical analysis. Several gene ontology (GO)
      categories were highly significantly differentially expressed including
      glycolysis (GO: 0006096; P<0.001) and the pigment biosynthetic process (GO:
      0046148; P<0.001), in which overexpression was associated with short-disease
      specific survival. Three overexpressed glycolytic genes, GAPDHS, GAPDH, and PKM2,
      and two pigment-related genes, TYRP1 and OCA2, were selected for validation. A
      significant difference in GAPDHS protein expression between short- and long-term
      survivors (P=0.021) and a trend for PKM2 (P=0.093) was observed in univariate
      analysis. Positive expression of at least two of four proteins (GAPDHS, GAPDH,
      PKM2, TYRP1) in immunohistochemical analysis was found to be an independent
      adverse prognostic factor for disease-specific survival (P=0.011). Our results
      indicate that this prognostic panel in combination with established risk factors
      may contribute to an improved prediction of patients with a high risk of relapse.

PMID- 24128790
TI  - Artifact avoidance for head impulse testing.

PMID- 24128792
TI  - Distinct neural mechanisms of tonal processing between musicians and non
      musicians.
AB  - OBJECTIVE: Both behavioral and neural responses to deviant melody endings can be
      enhanced through musical training. Yet it is unknown whether there are any
      differences in the neural responses of musicians and non-musicians given no
      difference in their behavioral responses. It is also unknown whether the melody
      preceding the fixed final tone influences the sense of completion. METHODS: We
      recorded neuromagnetic responses in ten musicians and ten non-musicians while
      they were evaluating the sense of completion associated with melodies. RESULTS:
      The sense of a melody's completion was influenced by the combination of the
      preceding melody and the ending tones. The N1 had shorter latency in musicians,
      while the sustained field had larger amplitudes in non-musicians. CONCLUSIONS:
      Musicians and non-musicians rated the sense of completion similarly, yet neural
      responses differed between the groups. SIGNIFICANCE: These findings suggest that
      neural processes in musicians and non-musicians may be distinct even when the
      sense of completion is assessed similarly in both groups. In other words, there
      might be specific tonal processing available to non-musicians which can
      compensate for their lack of musical training.

PMID- 24128791
TI  - A study of adaptation mechanisms based on ABR recorded at high stimulation rate.
AB  - OBJECTIVE: This paper analyzes the fast and slow mechanisms of adaptation through
      a study of latencies and amplitudes on ABR recorded at high stimulation rates
      using the randomized stimulation and averaging (RSA) technique. METHODS: The RSA
      technique allows a separate processing of auditory responses, and is used, in
      this study, to categorize responses according to the interstimulus interval (ISI)
      of their preceding stimulus. The fast and slow mechanisms of adaptation are
      analyzed by the separated responses methodology, whose underlying principles and
      mathematical basis are described in detail. RESULTS: The morphology of the ABR is
      influenced by both fast and slow mechanisms of adaptation. These results are
      consistent with previous animal studies based on spike rate. CONCLUSIONS: Both
      fast and slow mechanisms of adaptation are present in all subjects. In addition,
      the distribution of the jitter and the sequencing of the stimuli may be critical
      parameters when obtaining reliable ABRs. SIGNIFICANCE: The separated responses
      methodology enables for the first time the analysis of the fast and slow
      mechanisms of adaptation in ABR obtained at stimulation rates greater than 100
      Hz. The non-invasive nature of this methodology is appropriate for its use in
      humans.

PMID- 24128793
TI  - Post-exercise exhaustion in Lambert-Eaton myasthenic syndrome.
AB  - OBJECTIVES: To study post-exercise exhaustion by decrement (PEE-D) systematically
      in 24 repetitive nerve stimulation (RNS) tests in 14 patients with Lambert-Eaton
      myasthenic syndrome (LEMS). METHODS: In the abductor digiti quinti muscle, the
      compound muscle action potential (CMAP) amplitude and 3Hz responses for 2s were
      obtained with the supramaximal stimulation at rest, immediately after (PE0), 30s
      after (PE30s), and at 1, 2, 3, and 4m after 10-s exercise. RESULTS: There was a
      377% increment in the CMAP amplitude at PE0 and a mild increment (+26%) at PE30s.
      A transient but significant improvement (-22%) in the decremental response was
      observed at PE0, and a gradual worsening of decrement in subsequent tests, with
      the worst decrement noted (-50%) at PE2m. CONCLUSION: PEE-D was found 2m after
      exercise in LEMS. SIGNIFICANCE: PEE-D may be physiologically closest to the
      reversible myasthenic fatigue after exercise observed in LEMS patients.

PMID- 24128794
TI  - Electrophysiological correlates of disobedience and feigning-like behaviour in
      motor imagery.
AB  - OBJECTIVE: To explore motor excitability changes induced by disobedience and
      feigning-like behaviour. METHODS: Healthy subjects participated in motor imagery
      tasks. They imagined either a maximum muscle relaxation (condition 1) or a pinch
      grip (condition 2). In other trials, they were instructed to disobey the command
      to imagine a pinch grip. Instead, they should either imagine a maximum muscle
      relaxation (condition 3) or think of something else which they could choose
      freely (condition 4). Transcranial magnetic stimulation was used to explore motor
      excitability during the different tasks. Motor evoked potential amplitudes were
      expressed as percentage of the task-free control condition (condition 5).
      RESULTS: Imagination of a pinch grip enhanced motor excitability, imagery of
      maximum muscle relaxation reduced motor excitability below the level of the
      control condition. In conditions 3 and 4, motor excitability was lower than in
      condition 2. However, motor excitability in condition 3 was higher than in
      condition 1. CONCLUSIONS: Healthy subjects successfully disobeyed the motor
      imagery command but failed to maintain the down-regulation of motor excitability
      when trying to imagine maximum muscle relaxation. SIGNIFICANCE: The results help
      to interpret the down-regulation of motor excitability found in patients with
      motor conversion disorder.

PMID- 24128795
TI  - Development and evaluation of a risk communication curriculum for medical
      students.
AB  - OBJECTIVE: To develop, pilot, and evaluate a curriculum for teaching clinical
      risk communication skills to medical students. METHODS: A new experience-based
      curriculum, "Risk Talk," was developed and piloted over a 1-year period among
      students at Tufts University School of Medicine. An experimental study of 2nd
      year students exposed vs. unexposed to the curriculum was conducted to evaluate
      the curriculum's efficacy. Primary outcome measures were students' objective
      (observed) and subjective (self-reported) risk communication competence; the
      latter was assessed using an Observed Structured Clinical Examination (OSCE)
      employing new measures. RESULTS: Twenty-eight 2nd-year students completed the
      curriculum, and exhibited significantly greater (p<.001) objective and subjective
      risk communication competence than a convenience sample of 24 unexposed students.
      New observational measures of objective competence in risk communication showed
      promising evidence of reliability and validity. The curriculum was resource
      intensive. CONCLUSION: The new experience-based clinical risk communication
      curriculum was efficacious, although resource-intensive. More work is needed to
      develop the feasibility of curriculum delivery, and to improve the measurement of
      competence in clinical risk communication. PRACTICE IMPLICATIONS: Risk
      communication is an important advanced communication skill, and the Risk Talk
      curriculum provides a model educational intervention and new assessment tools to
      guide future efforts to teach and evaluate this skill.

PMID- 24128797
TI  - Real time ultrasound guided endotracheal intubation should strive for
      identification of esophageal intubation.

PMID- 24128798
TI  - Comparison of two teaching methods for cardiac arrhythmia interpretation among
      nursing students.
AB  - AIM: The aim of this study was to compare the six-stage method (SSM) for
      instructing primary cardiac arrhythmias interpretation to students without basic
      electrocardiogram (ECG) knowledge with a descriptive teaching method in a single
      educational intervention. METHODS: This is a randomized trial. Following a brief
      instructional session, undergraduate nursing students, assigned to group A (SSM)
      and group B (descriptive teaching method), undertook a written test in cardiac
      rhythm recognition, immediately after the educational intervention (initial
      exam). Participants were also examined with an unannounced retention test (final
      exam), one month after instruction. Altogether 134 students completed the study.
      Interpretation accuracy for each cardiac arrhythmia was assessed. RESULTS: Mean
      score at the initial exam was 8.71+/-1.285 for group A and 8.74+/-1.303 for group
      B. Mean score at the final exam was 8.25+/-1.46 for group A vs 7.84+/-1.44 for
      group B. Overall results showed that the SSM was equally effective with the
      descriptive teaching method. The study showed that in each group bradyarrhythmias
      were identified correctly by more students than tachyarrhythmias. No significant
      difference between the two teaching methods was seen for any specific cardiac
      arrhythmia. CONCLUSIONS: The SSM effectively develops staff competency for
      interpreting common cardiac arrhythmias in students without ECG knowledge. More
      research is needed to support this conclusion and the method's effectiveness must
      be evaluated if being implemented to trainee groups with preexisting basic ECG
      interpretation knowledge.

PMID- 24128799
TI  - Reply to letter: Real-time tracheal ultrasonography for confirmation of
      endotracheal tube placement during cardiopulmonary resuscitation.

PMID- 24128800
TI  - The incidence and significance of bacteremia in out of hospital cardiac arrest.
AB  - BACKGROUND: The most common etiology of cardiac arrest is presumed of myocardial
      origin. Recent retrospective studies indicate that preexisting pneumonia, a form
      of sepsis, is frequent in patients who decompensate with abrupt cardiac arrest
      without preceding signs of septic shock, respiratory failure or severe metabolic
      disorders shortly after hospitalization. The contribution of pre-existing
      infection on pre and post cardiac arrest events remains unknown and has not been
      studied in a prospective fashion. We sought to examine the incidence of pre
      existing infection in out-of hospital cardiac arrest (OHCA) and assess
      characteristics associated with bacteremia, the goal standard for presence of
      infection. METHODS AND RESULTS: We prospectively observed 250 OHCA adult patients
      who presented to the Emergency Department (ED) between 2007 and 2009 to an urban
      academic teaching institution. Bacteremia was defined as one positive blood
      culture with non-skin flora bacteria or two positive blood cultures with skin
      flora bacteria. 77 met pre-defined exclusion criteria. Of the 173 OHCA adults, 65
      (38%) were found to be bacteremic with asystole and PEA as the most common
      presenting rhythms. Mortality in the ED was significantly higher in bacteremic
      OHCA (75.4%) compared to non-bacteremic OHCA (60.2%, p<0.05). After adjustment
      for potential confounders, predictive factors associated with bacteremic OHCA
      were lower initial arterial pH, higher lactate, WBC, BUN and creatinine.
      CONCLUSIONS: Over one-third of OHCA adults were bacteremic upon presentation.
      These patients have greater hemodynamic instability and significantly increased
      short-term mortality. Further studies are warranted to address the epidemiology
      of infection as possible cause of cardiac arrest.

PMID- 24128801
TI  - Oral microbiota and systemic disease.
AB  - It is well known that bacteria are the primary cause of infectious diseases,
      however, evidence is emerging that these organisms are also indirectly
      responsible for several diseases including cancer and rheumatoid arthritis. The
      oral cavity is home to several million bacteria that can cause two major diseases
      periodontitis and caries. The relationship between periodontopathic bacteria and
      systemic diseases has been explored for several years. The concept of the oral
      cavity as a source of distant infection has been debated for at least a century.
      This review will discuss the historic aspects of the development of the focal
      infection theory, the reasons for its demise, its re-emergence and current
      status. 

PMID- 24128802
TI  - Imaging dose assessment for IGRT in particle beam therapy.
AB  - INTRODUCTION: Image-guided advanced photon and particle beam treatments are
      promising options for improving lung treatments. Extensive use of imaging
      increases the overall patient dose. The aim of this study was to determine the
      imaging dose for different IGRT solutions used in photon and particle beam
      therapy. MATERIAL AND METHODS: Measurements were performed in an Alderson phantom
      with TLDs. Clinically applied protocols for orthogonal planar kV imaging,
      stereoscopic imaging, CT scout views, fluoroscopy, CT, 4D-CT and CBCT were
      investigated at five ion beam centers and one conventional radiotherapy
      department. The overall imaging dose was determined for a patient undergoing a
      lung tumor irradiation with institute specific protocols. RESULTS: OAR doses
      depended on imaging modality and OAR position. Dose values were in the order of 1
      mGy for planar and stereoscopic imaging and 10-50 mGy for volumetric imaging,
      except for one CBCT device leading to lower doses. The highest dose per exam (up
      to 150 mGy to the skin) was recorded for a 3-min fluoroscopy. DISCUSSION:
      Modalities like planar kV or stereoscopic imaging result in very low doses (~ 1
      mGy) to the patient. Imaging a moving target during irradiation, low-dose
      protocols and protocol optimization can reduce the imaging dose to the patient
      substantially.

PMID- 24128803
TI  - Reproducibility of target coverage in stereotactic spot scanning proton lung
      irradiation under high frequency jet ventilation.
AB  - PURPOSE: To investigate scanned-beam proton dose distribution reproducibility in
      the lung under high frequency jet ventilation (HFJV). MATERIALS AND METHODS: For
      11 patients (12 lesions), treated with single-fraction photon stereotactic
      radiosurgery under HFJV, scanned-beam proton plans were prepared with the TRiP98
      treatment planning system using 2, 3-4 and 5-7 beams. The planning objective was
      to deliver at least 95% of the prescription of 33 Gy (RBE) to 98% of the PTV.
      Plans were subsequently recomputed on localization CT scans. Additionally, for
      selected cases, the effects of range uncertainties were investigated. RESULTS:
      Median GTV V(98%) was 98.7% in the original 2-field plans and 93.7% in their
      recomputation (p=0.039). The respective values were 99.0% and 98.0% (p=0.039) for
      the 3-4-field plans and 100.0% and 99.6% (p=0.125) for the 5-7-field plans. CT
      calibration uncertainties of +/-3.5% led to a GTV V(98%) reduction below 1.5
      percentual points in most cases and reaching 3 percentual points for 2-field
      plans with beam undershoot. CONCLUSIONS: Through jet ventilation, reproducible
      tumor fixation for proton radiotherapy of lung lesions is achievable, ensuring
      excellent target coverage in most cases. In few cases, non-optimal patient setup
      reproducibility induced density changes across beam entrance channels, leading to
      dosimetric deterioration between planning and delivery.

PMID- 24128804
TI  - Intra-fraction motion of the prostate during treatment with helical tomotherapy.
AB  - BACKGROUND AND PURPOSE: To measure the geometric uncertainty resulting from intra
      fraction motion and intra-observer image matching, for patients having image
      guided prostate radiotherapy on TomoTherapy. MATERIAL AND METHODS: All patients
      had already been selected for prostate radiotherapy on TomoTherapy, with daily MV
      CT imaging. The study involved performing an additional MV-CT image at the end of
      treatment, on 5 occasions during the course of 37 treatments. 54 patients were
      recruited to the study. A new formula was derived to calculate the PTV margin for
      intra-fraction motion. RESULTS: The mean values of the intra-fraction differences
      were 0.0mm, 0.5mm, 0.5mm and 0.0 degrees  for LR, SI, AP and roll, respectively.
      The corresponding standard deviations were 1.1mm, 0.8mm, 0.8mm and 0.6 degrees 
      for systematic uncertainties (Sigma), 1.3mm, 2.0mm, 2.2mm and 0.3 degrees  for
      random uncertainties (sigma). This intra-fraction motion requires margins of
      2.2mm in LR, 2.1mm in SI and 2.1mm in AP directions. Inclusion of estimates of
      the effect of rotations and matching errors increases these margins to
      approximately 4mm in LR and 5mm in SI and AP directions. CONCLUSIONS: A new
      margin recipe has been developed to calculate margins for intra-fraction motion.
      This recipe is applicable to any measurement technique that is based on the
      difference between images taken before and after treatment.

PMID- 24128805
TI  - Flattening-filter-free intensity modulated breath-hold image-guided SABR
      (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot.
AB  - Hypofractionated image-guided stereotactic ablative radiotherapy (igSABR) is
      effective in small lung/liver lesions. Computer-assisted breath-hold reduces
      intrafraction motion but, as every gating/triggering strategy, reduces the duty
      cycle, resulting in long fraction times if combined with intensity-modulated
      radiotherapy (IMRT). 10 MV flattening-filter-free IMRT reduces daily fraction
      duration to <10 min for single doses of 5-20 Gy.

PMID- 24128806
TI  - Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung
      cancer; systematic review and comparison with a surgical cohort.
AB  - BACKGROUND AND PURPOSE: To assess the efficacy of stereotactic ablative
      radiotherapy (SABR) for the treatment of non-small cell lung cancer (NSCLC)
      through a systematic review of all relevant publications from 2006 to the present
      compared to controls treated with surgery. In the absence of Grade I evidence,
      the objective outcome data should form the basis for planning future studies and
      commissioning SABR services. MATERIALS AND METHODS: Standard systematic review
      methodology extracting patient and disease characteristics, treatment and outcome
      data from published articles reporting patient data from populations of 20 or
      more Stage I NSCLC patients treated with SABR with a median follow up of minimum
      of 1 year. The individual outcome measures were corrected for stage and summary
      weighted outcome data were compared to outcome data from a large International
      Association for the Study of Lung Cancer (IASLC) cohort matched for stage of
      disease with survival as the principal endpoint and local control (local
      progression free survival - local PFS) as the secondary endpoint. RESULTS: Forty
      five reports containing 3771 patients treated with SABR for NSCLC were identified
      that fulfilled the selection criteria; both survival and staging data were
      reported in 3171 patients. The 2 year survival of the 3201 patients with
      localized stage I NSCLC treated with SABR was 70% (95% CI: 67-72%) with a 2 year
      local control of 91% (95% CI: 90-93%). This was compared to a 68% (95% CI: 66-70)
      2 year survival of 2038 stage I patients treated with surgery. There was no
      survival or local PFS difference with different radiotherapy technologies used
      for SABR. CONCLUSIONS: Systematic review of a large cohort of patients with stage
      I NSCLC treated with SABR suggests that survival outcome in the short and medium
      term is equivalent to surgery for this population of patients regardless of co
      morbidity. As selection bias cannot be assessed from the published reports and
      treatment related morbidity data are limited, a direct comparison between the two
      treatment approaches should be a priority. In the meantime, SABR can be offered
      to stage I patients with NSCLC as an alternative to surgery.

PMID- 24128807
TI  - Response to Dahele and Senan.

PMID- 24128809
TI  - The regio- and stereo-selective reduction of steroidal 4-en-3-ones using
      Na2S2O4/NaHCO3 and CuCl/NaBH4.
AB  - This paper describes the regio- and stereoselective reduction of ?4-3-keto moiety
      in certain steroids using Na2S2O4/NaHCO3 and CuCl/NaBH4, respectively. Using
      either one of the two reduction agents in the reaction, the 17-substituents in
      the D ring were observed to have clearly influenced the stereoselective reduction
      of 4-ene in the A ring by the so-called conformational transmission effect.
      Na2S2O4/NaHCO3 regioselectively reduced CC at 4-position of 17-substituted
      androst-4-en-3-one derivatives to 5alpha-H-3-one as the main isomer. And as an
      extended application, Epiandrosterone (11) was further synthesized from androst-4
      en-3,17-dione (AD) via four steps. The total yield from this was about 45%. In
      the presence of CuCl/NaBH4, ?4-3-keto conjugated reduction of 17-spirocyclic
      ethylene ketal protected androst-4-en-3-one derivatives mainly produced 3alpha
      hydroxy-5beta-H isomers, at a yield around 81%. Considering the scaffold
      configuration of 3alpha-hydroxy-5beta-H moiety coincided with that of bile acid
      analogs, this selective reduction could also be used as an alternative method for
      the synthetic study of bile acids using AD and its derivatives, which are from
      the microorganism degradation of natural sterols, as the potential materials.
      Meanwhile, configurations of the reductive compounds 5b, 6b, 9, 10 and 17e were
      identified by X-ray diffraction.

PMID- 24128808
TI  - Cetuximab in combination with chemoradiotherapy in Chinese patients with non
      resectable, locally advanced esophageal squamous cell carcinoma: a prospective,
      multicenter phase II trail.
AB  - BACKGROUND AND PURPOSE: This multicenter phase II trial investigated cetuximab
      combined with chemoradiotherapy in patients with esophageal squamous cell
      carcinoma (ESCC). MATERIAL AND METHODS: Eligible patients with non-resectable,
      locally-advanced ESCC received cetuximab 400mg/m(2) loading dose on day 1; and on
      day 1 of the 2nd-7th weeks: cetuximab 250mg/m(2), paclitaxel 45mg/m(2), and
      cisplatin 20mg/m(2), concurrent with 59.4Gy/33 fractions of radiation therapy.
      Primary endpoint was clinical response rate. Secondary endpoints included overall
      survival (OS), progression-free survival (PFS), safety, and KRAS status. RESULTS:
      Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical
      response: 29 complete response and 15 partial response. One-year PFS and OS of 45
      evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS
      were 74.87% and 80.00%, respectively. Non-hematologic adverse events were
      generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue
      (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included
      neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50
      evaluated samples. CONCLUSIONS: Cetuximab can be safely administered with
      chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical
      response rate.

PMID- 24128810
TI  - Syncope associated with documented paroxysmal atrioventricular block reproduced
      by adenosine 5' triphosphate injection.
AB  - AIMS: We sought to investigate in patients with syncope the relationship between
      documented paroxysmal atrioventricular block (AVB) of unknown mechanism and AVB
      induced by adenosine triphosphate (ATP) injection. METHODS AND RESULTS: We
      selected patients >45 years free of structural heart disease with syncope related
      to paroxysmal AVB documented by Holter or in-hospital monitoring, but without any
      trigger suggestive of vasovagal origin and with normal baseline
      electrocardiogram. Adenosine triphosphate test was performed according to the
      usual protocol. Nine patients (all females; mean age 66 +/- 14.6 years; range: 48
      81 years) matching the abovementioned criteria particularly documented
      spontaneous complete AVB with long ventricular pauses. Their mean QRS duration
      was 86.6 +/- 14.1 ms and the mean PR interval was 161 +/- 21.3 ms. In all
      patients, ATP induced a long ventricular pause related to AVB (mean duration 13.2
      s; range from 7 to 56 s). After a mean follow-up duration of 42 +/- 36 months,
      electrocardiogram (ECG) remained unchanged without progression to permanent AVB
      or appearance of intraventricular conduction disturbances. CONCLUSION: Some
      patients, predominantly older females, with 'normal' heart and ECG, have syncope
      associated with spontaneous AVB of unknown origin reproduced during the ATP test.
      They do not develop permanent AVB during follow-up. This unusual behaviour could
      be interpreted as an abnormal susceptibility to ATP and these patients could be
      considered to have 'ATP-sensitive AVB'. In this subgroup of syncope patients ATP
      test is useful.

PMID- 24128811
TI  - Andersen-Tawil syndrome, scarier for the doctor than for the patient? Who, when,
      and how to treat.

PMID- 24128812
TI  - Late re-conduction sites in the second session after pulmonary vein isolation
      using adenosine provocation for atrial fibrillation.
AB  - AIMS: Intravenous adenosine triphosphate (ATP) administration could reveal
      dormant conduction (DC) gaps on the ablation line of a pulmonary vein isolation
      (PVI). We compared the ATP-provoked DC sites in the initial PVI with the PV re
      conduction sites in the second session in patients with paroxysmal atrial
      fibrillation (AF). METHODS AND RESULTS: We conducted a multicenter, observational
      study from a prospective registry undergoing AF ablation. A total of 110
      consecutive drug-refractory paroxysmal AF patients were enroled in this study.
      Dormant conduction was detected by an ATP provocation of up to 40 mg during a
      continuous isoproterenol infusion (0.5-2 MUg/min). The DC sites at each of the
      right and left PVs were precisely determined by using double spiral catheters
      under the guidance of a three-dimensional constructed anatomical mapping system.
      In the initial session, DC was observed in 35 patients (31.8%, 1.3 gaps/patient),
      and the sites of the DC were commonly observed in the carina region (43.5%).
      Atrial fibrillation recurrence was confirmed in 33 patients (30.0%) during follow
      up (27.1 months), and a second session was performed in 24 of 33 patients
      (70.6%). In the second session, the re-conduction sites were also commonly
      observed in the carina region (59.5%). CONCLUSION: The carina region was still a
      dominant re-conduction site even after the elimination of any ATP-provoked DC in
      the index procedure.

PMID- 24128813
TI  - Exploring a potential palonosetron allosteric binding site in the 5-HT(3)
      receptor.
AB  - Palonosetron (Aloxi) is a potent second generation 5-HT(3) receptor antagonist
      whose mechanism of action is not yet fully understood. Palonosetron acts at the 5
      HT(3) receptor binding site but recent computational studies indicated other
      possible sites of action in the extracellular domain. To test this hypothesis we
      mutated a series of residues in the 5-HT3A receptor subunit (Tyr(73), Phe(130),
      Ser(163), and Asp(165)) and in the 5-HT3B receptor subunit (His(73), Phe(130),
      Glu(170), and Tyr(143)) that were previously predicted by in silico docking
      studies to interact with palonosetron. Homomeric (5-HT(3)A) and heteromeric (5
      HT(3)AB) receptors were then expressed in HEK293 cells to determine the potency
      of palonosetron using both fluorimetric and radioligand methods to test function
      and ligand binding, respectively. The data show that the substitutions have
      little or no effect on palonosetron inhibition of 5-HT-evoked responses or
      binding. In contrast, substitutions in the orthosteric binding site abolish
      palonosetron binding. Overall, the data support a binding site for palonosetron
      at the classic orthosteric binding pocket between two 5-HT3A receptor subunits
      but not at allosteric sites previously identified by in silico modelling and
      docking.

PMID- 24128814
TI  - Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine
      Homoisoflavonoid hybrids.
AB  - A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and
      evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases
      (MAOs). Most of the compounds were found to be potent against both ChEs and MAO
      B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and
      (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent
      against AChE and MAO-B with IC50 values of 67.9 nM and 0.401 MUM, respectively.
      This compound was observed to cross the blood-brain barrier (BBB) in a parallel
      artificial membrane permeation assay for the BBB (PAMPA-BBB). The results
      indicated that compound 8b is an excellent multifunctional promising compound for
      development of novel drugs for Alzheimer's disease (AD).

PMID- 24128815
TI  - Ligand modifications to reduce the relative resistance of multi-drug resistant
      HIV-1 protease.
AB  - Proper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for
      HIV infection and viral replication. This feature has made HIV-1 protease an
      attractive target for antiretroviral drug design for the treatment of HIV-1
      infected patients. To examine the role of the P1 and P1'positions of the
      substrate in inhibitory efficacy of multi-drug resistant HIV-1 protease 769 (MDR
      769), we performed a series of structure-function studies. Using the original
      CA/p2 cleavage site sequence, we generated heptapeptides containing one reduced
      peptide bond with an L to F and A to F double mutation at P1 and P1' (F-r-F), and
      an A to F at P1' (L-r-F) resulting in P1/P1' modified ligands. Here, we present
      an analysis of co-crystal structures of CA/p2 F-r-F, and CA/p2 L-r-F in complex
      with MDR 769. To examine conformational changes in the complex structure,
      molecular dynamic (MD) simulations were performed with MDR769-ligand complexes.
      MD trajectories show the isobutyl group of both the lopinavir analog and the
      CA/p2 L-r-F substrate cause a conformational change of in the active site of MDR
      769. IC50 measurements suggest the non identical P1/P1' ligands (CA/p2 L-r-F and
      lopinavir analog) are more effective against MDR proteases as opposed to
      identical P1/P1'ligands. Our results suggest that a non identical
      P1/P1'composition may be more favorable for the inhibition of MDR 769 as they
      induce conformational changes in the active site of the enzyme resulting in
      disruption of the two-fold symmetry of the protease, thus, stabilizing the
      inhibitor in the active site. 

PMID- 24128816
TI  - Design of fluorinated 5-HT(4)R antagonists: influence of the basicity and
      lipophilicity toward the 5-HT(4)R binding affinities.
AB  - Analogues of potent 5-HT(4)R antagonists possessing a fluorinated N-alkyl chain
      have been synthesized in order to investigate the effect of the resulting change
      in basicity and lipophilicity on the affinity and selectivity profile. We
      demonstrate that for this series, the affinity is decreased with decreased
      basicity of the piperidine's nitrogen atom. In contrast, the resulting increase
      in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3
      Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind
      to the 5-HT(4)R while maintaining their pharmacological profile and selectivity
      toward other 5-HT receptors.

PMID- 24128817
TI  - A comprehensive framework for the assessment of new end uses in recycled water
      schemes.
AB  - Nowadays, recycled water has provided sufficient flexibility to satisfy short
      term freshwater needs and increase the reliability of long-term water supplies in
      many water scarce areas, which becomes an essential component of integrated water
      resources management. However, the current applications of recycled water are
      still quite limited that are mainly associated with non-potable purposes such as
      irrigation, industrial uses, toilet flushing and car washing. There is a large
      potential to exploit and develop new end uses of recycled water in both urban and
      rural areas. This can greatly contribute to freshwater savings, wastewater
      reduction and water sustainability. Consequently, the paper identified the
      potentials for the development of three recycled water new end uses, household
      laundry, livestock feeding and servicing, and swimming pool, in future water use
      market. To validate the strengths of these new applications, a conceptual
      decision analytic framework was proposed. This can be able to facilitate the
      optional management strategy selection process and thereafter provide guidance on
      the future end use studies within a larger context of the community, processes,
      and models in decision-making. Moreover, as complex evaluation criteria were
      selected and taken into account to narrow down the multiple management
      alternatives, the methodology can successfully add transparency, objectivity and
      comprehensiveness to the assessment. Meanwhile, the proposed approach could also
      allow flexibility to adapt to particular circumstances of each case under study. 

PMID- 24128818
TI  - An Internet-based program to enhance motivation to change in females with
      symptoms of an eating disorder: a randomized controlled trial.
AB  - BACKGROUND: Previous research has demonstrated an association between low
      motivation to change and an unfavorable treatment outcome in patients with an
      eating disorder. Consequently, various studies have examined the effects of
      motivational enhancement therapy (MET) on motivation to change and treatment
      outcome in eating disorders. In each of these studies, MET was administered in a
      face-to-face setting. However, because of its anonymity and ease of access, the
      internet provides several advantages as the format for such an intervention.
      Therefore, the current study investigated the effects of an internet-based
      program ('ESS-KIMO') to enhance motivation to change in eating disorders. METHOD:
      In total, 212 females were accepted for participation and assigned randomly to
      the intervention condition (n = 103) or waiting-list control condition (n = 109).
      The intervention consisted of six online MET sessions. Before and after the
      intervention or waiting period respectively, participants completed the Eating
      Disorder Examination Questionnaire (EDE-Q), the Stages of Change Questionnaire
      for Eating Disorders (SOCQ-ED), the Pros and Cons of Eating Disorders Scale (P
      CED), the Self-Efficacy Scale (SES), and the Rosenberg Self-Esteem Scale (RSES).
      A total of 125 participants completed the assessment post-treatment. Completer
      analyses and intent-to-treat analyses were performed. RESULTS: Significant time *
      group interactions were found, indicating a stronger increase in motivational
      aspects and self-esteem, in addition to a stronger symptom reduction on some
      measures from pre- to post-treatment in the intervention group compared to the
      control group. CONCLUSIONS: Internet-based approaches can be considered as useful
      for enhancing motivation to change in eating disorders and for yielding initial
      symptomatic improvement.

PMID- 24128819
TI  - Predictors of low haematocrit among repeat donors in Sao Paulo, Brazil: eleven
      year longitudinal analysis.
AB  - BACKGROUND AND OBJECTIVES: Few longitudinal studies have examined the long-term
      effect on deferral for low haematocrit (Hct) or haemoglobin, indicators of
      presence of anaemia. This study retrospectively analysed 11 years of donation
      history to examine predictors related to such deferrals among repeat blood
      donors. MATERIALS AND METHODS: We included 385,357 donors with at least two
      visits to the blood centre between January 1996 and December 2006 who were not
      deferred due to haematocrit at their first visit. We evaluated variables related
      to the development of low Hct (LHct-below 38% for females and 39% for males)
      after whole blood donations. RESULTS: Over the 11-year period, 3,850 (1.5%) of
      the 252,301 males and 18,104 (13.6%) of the 133,056 females were deferred due to
      LHct at some point after their first donation. Genders, age, baseline Hct, Hct at
      the visit immediately before deferral due to LHct, and interval between
      donations, were associated with higher rates of development of LHct in repeat
      donors. CONCLUSION: Our analysis showed that deferral due to low Hct levels in
      repeat blood donors is highly prevalent in Brazil. Assigning longer donations
      intervals based on the Hct levels at the qualifying donation or supplementing
      iron to donors at risk may decrease deferral rate of donors with low Hct.

PMID- 24128820
TI  - Palliative care in Taiwan.

PMID- 24128821
TI  - A report on the long-term use of fentanyl pectin nasal spray in patients with
      recurrent breakthrough pain.
AB  - CONTEXT: As patients with cancer are living longer, there is a need to ensure
      that treatments used for palliative care are well tolerated and effective during
      long-term use. OBJECTIVES: To investigate the long-term use of fentanyl pectin
      nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in
      patients receiving regular opioid therapy. METHODS: Adult patients (N = 401)
      taking at least 60 mg/day oral morphine or equivalent, experiencing one to four
      episodes of BTPc a day, entered an open-label long-term study (NCT00458510).
      Patients had either completed an FPNS randomized controlled trial or were newly
      identified. Of these, 171 patients continued into an extension study. Up to four
      episodes of BTPc a day were treated with FPNS at 100-800 MUg titrated doses.
      During the extension study, patients visited the clinic every four weeks for
      assessment and reporting of adverse events (AEs). RESULTS: There were 163
      patients with documented FPNS use. The mean duration of use was 325 days; 46
      patients used FPNS for >=360 days; the maximum duration was 44 months. Seventy
      percent of patients did not change their FPNS dose; 2% of patients withdrew from
      the study because of the lack of efficacy. The most common AEs, aside from
      disease progression, were insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and
      peripheral edema, 9.4%. The overall incidence of FPNS-related AEs was 11.1%, the
      most common being constipation (4.1%), with no apparent dose relationship. Ten
      patients (5.8%) experienced nasal AEs, most of which were mild or moderate.
      CONCLUSION: FPNS appeared to provide sustained benefit and was well tolerated
      during long-term treatment of BTPc.

PMID- 24128822
TI  - Acetaminophen (paracetamol).
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- 24128823
TI  - Prostate cancer: a high value target for cost containment.

PMID- 24128824
TI  - Legends in urology.

PMID- 24128825
TI  - Ureteral diverticulum: a review of the current literature.
AB  - INTRODUCTION: Ureteral diverticulum is a rare urological condition with only 45
      cases described in the literature. These previously reported cases vary in their
      presentation, diagnosis and management and there is no consensus in the
      literature on the best diagnostic tool available. We describe our experience on
      diagnosing and managing this condition in two patients and provide a descriptive
      review of the current literature on ureteral diverticulum. MATERIALS AND METHODS:
      A Medline search was performed to identify all reported cases of ureteral
      diverticulum. Key words used were: ureteral diverticulum; abortive bifid ureter;
      congenital diverticulum; acquired diverticulum. We also reviewed the records of
      two patients who presented consecutively to our institution with a ureteral
      diverticulum. The clinical and radiological characteristics of this entity were
      then evaluated. RESULTS: Forty-one manuscripts were identified, encompassing
      single case reports and case series, the largest of which contained seven
      patients. Two additional cases were diagnosed in our institution; a true
      congenital diverticulum and an abortive bifid ureter which is synonymous with a
      true ureteral diverticulum. Both were uncomplicated cases and were managed
      conservatively. Retrograde pyelography was used for definitive diagnosis of this
      lesion. CONCLUSION: Ureteral diverticulum may present as an incidental finding or
      with a secondary complication. Conservative management is advocated in the
      literature for non-complicated cases. Retrograde pyelography is our diagnostic
      tool of choice.

PMID- 24128826
TI  - Anterior tumors of the prostate: diagnosis and significance.
AB  - INTRODUCTION: Prostate biopsies are usually taken from the peripheral rather than
      anterior region of the prostate. Consequently, tumors originating from the
      anterior apical region and transition zones may be under-sampled. We examined
      whether addition of transrectal anterior biopsy (TAB) would improve efficacy of
      prostate biopsies. MATERIALS AND METHODS: Simulations of TAB and sextant biopsy
      (SB) were performed using computer models of 86 autopsy prostates (AP) and 40
      radical prostatectomy (RP) specimens. TAB was obtained bilaterally from apex,
      mid, and base regions by advancing the biopsy needle 5 mm-35 mm beyond the
      prostatic capsule. A phase I clinical trial with 114 patients was conducted to
      determine the performance of an extended biopsy protocol consisting of TAB, SB,
      and laterally-directed biopsy (LDB). RESULTS: The overall cancer detection rates
      of SB and TAB were 33% and 55% for AP series (p = 0.00003); 60% and 88% for RP
      series (p = 0.006). Alternatively, SB + bilateral apical TAB and SB + bilateral
      mid TAB had cancer detection rates of 45% and 42% for AP series; 80% and 78% for
      RP series. The extended biopsy protocol detected cancer in 33% (38/114) of
      patients with 29, 25, and 15 diagnosed by SB, LDB, and bilateral apical TAB,
      respectively. Patients diagnosed by bilateral apical TAB versus SB (p = 0.01) and
      LDB (p = 0.02) were statistically significant. Without bilateral apical TAB, the
      overall cancer detection rate decreased to 30% (34/114). CONCLUSIONS: Inclusion
      of bilateral TAB from apical region for first time and repeat prostate biopsies
      may increase diagnosis of prostate cancer. The clinical significance of these
      findings needs further investigations and clinical follow up.

PMID- 24128827
TI  - First 100 cases at a low volume prostate brachytherapy institution: learning
      curve and the importance of continuous quality improvement.
AB  - INTRODUCTION: We report the first 100 patients who underwent prostate
      brachytherapy as monotherapy with 125I at an institution with moderate volume
      radical prostatectomy but low volume brachytherapy (<2 cases per month). Learning
      curve and quality improvement was assessed by way of achieving prescription dose
      targets. MATERIALS AND METHODS: From May 2002 to August 2006, 100 patients
      underwent prostate 125I brachytherapy monotherapy via preplanned approach.
      Preoperative planned dose to 100% of prostate gland (D100) was 145 Gy and
      postoperative confirmed dose was assessed by computed tomography. The cohort was
      divided into quartiles and recurrence was assessed using Kaplan-Meier analysis.
      RESULTS: Patient quartiles were of similar age and Gleason grade, while PSA was
      slightly higher in the first group. Postoperative D90 increased after the first
      quartile (p = < 0.0001) reaching targeted values. Kaplan-Meier survival analysis
      revealed that 5 year recurrence-free survivals by Phoenix definition was 96%-100%
      in all groups while by ASTRO definition there was a decrease in recurrence for
      later cases. CONCLUSIONS: At our low volume institution during the first 100
      brachytherapy cases, a learning curve for radiation dosimetry was evident, which
      improved after 25 patients. Preplanned dose-volume parameters were adjusted,
      enabling the achievement of post-implant goals emphasizing the importance of
      continuous quality improvement. Although recurrence data is limited by sample
      size and moderate follow up, there was a discrepancy between the Phoenix and
      ASTRO definition when evaluating recurrence.

PMID- 24128828
TI  - The path to quality prostate seed implants.

PMID- 24128829
TI  - Association of tumor size with metastatic potential and survival in patients with
      adrenocortical carcinoma: an analysis of the National Cancer Database.
AB  - INTRODUCTION: To assess the impact of size at presentation in patients with
      adrenocortical carcinoma (ACC) on rates of synchronous metastatic disease and
      survival following resection using a large administrative dataset. MATERIALS AND
      METHODS: We queried the National Cancer Database (NCDB) dataset to assemble a
      cohort of patients with ACC based on SEER staging (1985-2000). Patients were
      stratified into three groups based on surgical tumor size cutoffs: < 4 cm, 4 cm-6
      cm, and > 6 cm. Rates of metastatic disease at presentation in all ACC patients
      as well as relative survival for patients after resection of localized lesions
      were calculated and compared among groups. RESULTS: A total of 2248 patients had
      available staging information for analysis. Tumor size at presentation did not
      relate to likelihood of non-localized disease at presentation (p = 0.09). A
      restricted cubic splines analysis revealed a clinically insignificant
      relationship between tumor size and advanced disease at presentation (OR = 1.02
      for each centimeter change in tumor size, p = 0.004, 95% CI 1.01-1.03). On
      multivariate analysis, only patient age (p < 0.01), and not tumor size, was a
      significant predictor of overall survival among patients undergoing resection of
      localized ACCs. CONCLUSIONS: Our data suggest that tumor size is imperfect in
      predicting presence of distant disease at presentation, nor does it consistently
      correlate with patient survival after resection of localized ACC.

PMID- 24128830
TI  - Internet program for facilitating dietary modifications limiting kidney stone
      risk.
AB  - INTRODUCTION: Certain dietary modifications limit the risk of stone recurrence.
      Compliance is an important component of dietary therapy for stone prevention, and
      self-efficacy is an important ingredient of compliance. We developed an internet
      program to facilitate dietary compliance for stone prevention and performed a
      pilot study to assess its effectiveness. MATERIALS AND METHODS: The internet
      program provides information regarding dietary modifications including increased
      fluid consumption, limited animal protein, sodium, and oxalate intake, and
      adequate calcium consumption. Participants record their daily food and fluid
      intake and receive immediate feedback as to whether they were compliant or not.
      Five adult calcium stone formers collected three 24 hour urine specimens on self
      selected diets, three 24 hour urine specimens while on a stone preventive
      metabolic diet, and three 24 hour urine specimens after utilizing the internet
      program for 1 month. Urinary stone risk parameters were measured, and data were
      analyzed using repeated measures ANOVA and Student's t test. RESULTS: All
      participants recorded their meals and snacks for each day and found the program
      easy to navigate. The mean time in hours from food consumption to log in was
      35.25 +/- 70.8 hours. There were no statistically significant differences in
      stone risk factors between the controlled and internet dietary phases. Oxalate
      excretion was significantly higher during the self-selected dietary intake (p =
      0.03). CONCLUSIONS: This pilot study demonstrates that subjects appear to be
      compliant with utilization of an interactive internet program for stone
      prevention with dietary modifications. In addition, improvement in certain stone
      risk parameters occurred.

PMID- 24128831
TI  - Comparison of midurethral sling outcomes with and without prolapse repair.
AB  - INTRODUCTION: To compare the outcome of single incision and retropubic
      midurethral slings when performed with and without concomitant repair of pelvic
      organ prolapse (POP). MATERIALS AND METHODS: A retrospective chart review was
      conducted of all midurethral slings performed with and without concomitant POP
      repair by a single provider from September 2008 to April 2010. Prolapse was
      repaired transvaginally with light-weight polypropylene mesh or robotically via
      sacrocolpopexy based on the nature of the prolapse and surgeon preference.
      Success of the sling procedure was defined as complete resolution of leakage or
      great improvement of leakage based on the Patient Global Impression of
      Improvement score. RESULTS: Eighty-nine patients underwent a midurethral sling
      procedure. Forty-five patients received a single incision sling, 18 of which had
      concomitant POP repair. Forty-four received a retropubic sling, 16 of which had
      concomitant POP repair. Successful treatment of SUI in the single incision sling
      group was 89% (24/27) which was not significantly different from the retropubic
      only sling group 93% (26/28), p = 0.61. However, a significant difference was
      seen in the successful treatment of SUI in the single incision sling plus
      prolapse repair group 67% (12/18) versus the retropubic sling plus prolapse
      repair group 94% (15/16), p = 0.05. CONCLUSION: We found a higher incidence of
      single incision mid-urethral sling failure when done at the same time as repair
      of pelvic organ prolapse in comparison to sling placement alone. There is no
      difference in the success of retropubic slings when done with or without
      concomitant prolapse repair.

PMID- 24128832
TI  - Percutaneous cryoablation for recurrent low grade renal cell carcinoma after
      failed nephron-sparing surgery.
AB  - INTRODUCTION: Partial nephrectomy has a 3%-4% incidence of local treatment
      failure. This study is to present a series of percutaneous cryoablation for
      locally recurrent renal cell carcinoma after partial nephrectomy. MATERIALS AND
      METHODS: Five consecutive patients were referred to our quarternary center's
      multidisciplinary Small Renal Mass (SRM) Center for assessment after failure of
      partial nephrectomy. Tumor size and location was noted. CT-guided cryoablation
      was performed using an argon/helium-based system (Healthtronics, Austin, Texas,
      USA). Patients were admitted overnight for observation. Patients were followed
      with serial imaging, laboratory tests and examination at our SRM Center. Tumor
      size, location, and nephrometry scores were documented for each patient. RESULTS:
      Four tumors were endophytic and one was exophytic. The median tumor size was 2.2
      cm (1.8 cm-4.0 cm). Nephrometry scores were 8a, 7x, 4p, 6x, 7p, and 6p prior to
      cryoablation. Median follow up after cryoablation was 32 months (20-39 months).
      One patient with a 4.0 cm endophytic tumor developed a second recurrence
      measuring 2.9 cm 13 months following ablation, which was managed successfully
      with repeat cryoablation with no evidence of disease after an additional 19
      months of follow up. Two patients developed self-limited hematuria which was
      conservatively managed. There were no other complications, and all patients
      remained at their pretreatment performance status. CONCLUSIONS: Percutaneous
      cryoablation appears to be a safe and effective nephron-sparing modality for
      control of locally recurrent disease following partial nephrectomy. Most
      recurrent tumors are endophytic. One patient suffered a second local recurrence,
      which was managed successfully with repeat cryoablation.

PMID- 24128833
TI  - Salvage ablation for partial nephrectomy failures.

PMID- 24128834
TI  - Failing to follow up: predicting patients that will "no-show" for medically
      advised imaging following endourologic stone surgery.
AB  - INTRODUCTION: The purpose of this study is to evaluate predictors of poor
      compliance after treatment of urinary stone disease. MATERIALS AND METHODS: This
      study was a retrospective analysis of patients who underwent stent removal
      following percutaneous nephrolithotomy (PCNL) or ureteroscopy (URS) between 2008
      2012. All patients were scheduled for follow up evaluation and renal ultrasound
      at 4-6 weeks following stent removal. Patients were stratified based on
      appointment compliance and demographic variables including gender, age, insurance
      type (Government Assisted Insurance [GAI] or Private Insurance [PI]), initial
      procedure, season, distance between home and clinic, average monthly gas price at
      follow up, and median education attainment. Logistic regression was performed to
      determine independent predictors of missed follow up. RESULTS: A total of 301
      patients were included, 153 women (51% female) with a mean age of 54 +/- 14.2
      years. Of the cohort, 22.6% (n = 68) did not return for follow up. GAI was the
      only variable associated with a greater risk of non-compliance on univariate
      analysis (OR 2.13 [95% CI 1.12-3.86] p = 0.011) and multivariate analysis (OR
      3.14.10 [95% CI 1.48-6.7], p < 0.01). Gender, age, procedure, season, distance,
      gas prices, and education were not significant predictors. CONCLUSION: In our
      study, evaluating characteristics associated with missed follow up after stent
      removal for PCNL and URS, possession of GAI was the only factor associated with
      non-compliance. Urologists should be aware that persons with GAI may be at
      increased risk of missed follow up and should use this information to target
      interventions to improve compliance.

PMID- 24128835
TI  - CyberKnife for inoperable renal tumors: Canadian pioneering experience.
AB  - INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under
      study regarding its clinical application in management of patients with kidney
      tumors. CyberKnife can accurately deliver ablative tumor radiation doses while
      preserving kidney function. We report Canada's first use of CyberKnife SABR
      system in treating primary kidney tumors. MATERIALS AND METHODS: Between January
      2011 and February 2012, we treated three patients with renal tumors using
      CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient
      had a recurrent tumor after two previous radiofrequency ablation treatments.
      Platinum seed fiducials were used for real time tumor tracking. Magnetic
      resonance imaging registration was used for tumor delineation in all cases. The
      patients were followed with regular renal scans and renal function tests.
      RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy
      in 3 fractions was delivered. The post treatment follow up times were 15 months,
      13 months and 12 months. Local control was obtained in all three patients. No
      acute or chronic toxicity was reported. Kidney functions remained unaffected
      after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of
      medically inoperable renal tumors or tumors in a solitary kidney.

PMID- 24128836
TI  - Renal radiosurgery: cautious optimism.

PMID- 24128837
TI  - Outcome of bilateral laparoscopic Fowler-Stephens orchidopexy for bilateral intra
      abdominal testes.
AB  - INTRODUCTION: To evaluate the outcome of bilateral laparoscopic Fowler-Stephens
      orchidopexy (BLFSO) for bilateral intra-abdominal testes. MATERIALS AND METHODS:
      Prospectively, all patients with bilateral intra-abdominal testes between 2006
      and 2010 were included in this study. Patients' data were analyzed for age,
      procedure whether single stage or staged Fowler-Stephens, intraoperative and
      postoperative complications, and follow up results. RESULTS: BLFSO was performed
      in a total of 48 testes in 24 boys with a median age of 31.6 months (range 12 to
      150). All procedures were performed on an outpatient basis. Of the 24 boys, six
      were managed with a single stage BLFSO. The remaining 18 patients were managed
      with staged Fowler-Stephens orchidopexy. Testicular position after laparoscopy
      was the mid lower scrotum in 43 testes, the remaining five testes retracted to
      the inguinal canal in three (required inguinal approach for orchidopexy) and to
      the neck of scrotum in two. Testicular atrophy was encountered in two testes with
      a follow up of 18 months postoperatively. CONCLUSIONS: Outpatient single stage or
      staged bilateral laparoscopic Fowler-Stephens orchidopexy were successful in
      managing boys with bilateral intra-abdominal testes.

PMID- 24128838
TI  - Laparoscopic orchidopexy for bilateral intra-abdominal testes.

PMID- 24128839
TI  - Robot assisted radical prostatectomy: how I do it. Part I: Patient preparation
      and positioning.
AB  - Radical prostatectomy remains the standard treatment for long term cure of
      clinically localized prostate cancer, offering excellent oncologic outcomes, with
      cancer-specific survival approaching 95% at 15 years after surgery. The
      introduction of the "da Vinci Robotic Surgical System" (Intuitive Surgical,
      Sunnyvale, CA, USA) has been another important step toward a minimally invasive
      approach to radical prostatectomy. Technologic peculiarities, such as three
      dimensional vision, wristed instrumentation with seven degrees of freedom of
      motion, lack of tremor, a 10x-magnification and a comfortable seated position for
      the surgeon has added value to the surgeon and patient. In this first part of a
      two article series, we describe preoperative patient preparation and positioning
      protocols for robot assisted radical prostatectomy (RARP) that are currently used
      in our institution (University of Montreal Hospital Center (CHUM)-Hopital St
      Luc). We use the four-arm da Vinci Si Surgical System. Our experience with RARP
      is now over 250 cases with the senior surgeon having performed over 1200 RARPs
      and we have continually refined our technique to improve patient outcomes.

PMID- 24128840
TI  - A magnetic mass within the bladder.
AB  - A search of the literature finds that there have been many case reports
      documenting a wide array of objects found within the bladder, ranging from
      magnets and paper clips to telephone and aluminum wire. The goal of treatment is
      to remove the object quickly, using the least invasive method possible.
      Therefore, the ideal treatment is removal through endoscopic means; however, in
      some cases, the size, mobility and shape of the foreign body can prevent its
      removal endoscopically and more invasive means must be employed. We present a
      case of a patient who inserted 150 magnetic spherical beads into his bladder. 

PMID- 24128841
TI  - Renal cell carcinoma presenting with brain metastasis from a 1.6 cm primary
      tumor.
AB  - Small renal cell carcinoma (RCC) tumors are believed to have a negligible risk of
      metastasis. We report on a 77-year-old man presenting with extremity weakness who
      was found to have a 2.5 cm brain metastasis from a subsequently discovered 1.6 cm
      clear cell RCC primary tumor. We review what is known about synchronous and
      metachronous metastasis from small renal tumors and prognostic features informing
      treatment for such lesions. 

PMID- 24128842
TI  - Adrenal lymphangioma: a rare cystic lesion of the adrenal.
AB  - We herein report the case of a left adrenal lymphangioma in a 52-year-old
      asymptomatic female and review the pertinent literature relatable to this rare,
      benign lesion. 

PMID- 24128843
TI  - Acute bilateral ureteral obstruction secondary to guaifenesin toxicity.
AB  - Several medications or their metabolites have been associated with urolithiasis,
      although overall they remain an infrequent cause of urolithiasis. Guaifenesin
      stones were originally reported as complexed with ephedrine, and subsequent
      reports have demonstrated pure guaifenesin stones, occurring after long term
      abuse. We report a case of a 23-year-old male who ingested a large, one time dose
      of guaifenesin, resulting in acute bilateral ureteral obstruction, which, to our
      knowledge, is the first such reported case in the literature. 

PMID- 24128844
TI  - Congenital urethral polyps in the pediatric population.
AB  - Congenital urethral polyps are a rare entity. Most commonly, they present as
      benign posterior urethral growths in the pediatric male patient. However, reports
      of urethral polyps in female patients or even those with an anterior urethral
      location can also be found in the literature. Patients can present with a
      spectrum of symptoms including dysuria, hematuria, and obstructive type urinary
      complaints. Diagnosis in these cases includes a combination of medical imaging
      (e.g. ultrasound, fluoroscopic, CT or MRI), direct endoscopic visualization, and
      final surgical pathology. Treatment involves surgical removal either via an
      endoscopic or open approach. 

PMID- 24128845
TI  - Molecular cloning and expression analysis of pig CD138.
AB  - CD138 (syndecan-1) interacts with various components of the extracellular matrix
      and associates with the actin cytoskeleton. In this study, we cloned pig CD138
      cDNA and determined its complete cDNA sequence. Pig CD138 cDNA contained an open
      reading frame (930 bp) encoding 309 amino acids with five well conserved putative
      glycosaminoglycan attachment sites, a putative cleavage site for matrix
      metalloproteinases, and conserved motifs involved in signal transduction among
      mammalian species. Pig CD138 mRNA was detected in various tissues, including
      lymphoid and non-lymphoid organs, indicating the multicellular functions of CD138
      in pigs. Western blot and flow cytometry analyses detected an approximate 35 kDa
      pig CD138 protein expressed on the cell surface. Further immunohistochemistry
      analysis revealed that CD138 expression was mainly observed in submucosa and
      lamina propria of the pig small intestine. Further study will be necessary to
      define the functional importance of CD138 during specific infectious diseases in
      pigs.

PMID- 24128846
TI  - Take a tree to the limit: the stress line.

PMID- 24128847
TI  - An imperative need for global change research in tropical forests.
AB  - Tropical forests play a crucial role in regulating regional and global climate
      dynamics, and model projections suggest that rapid climate change may result in
      forest dieback or savannization. However, these predictions are largely based on
      results from leaf-level studies. How tropical forests respond and feedback to
      climate change is largely unknown at the ecosystem level. Several complementary
      approaches have been used to evaluate the effects of climate change on tropical
      forests, but the results are conflicting, largely due to confounding effects of
      multiple factors. Although altered precipitation and nitrogen deposition
      experiments have been conducted in tropical forests, large-scale warming and
      elevated carbon dioxide (CO2) manipulations are completely lacking, leaving many
      hypotheses and model predictions untested. Ecosystem-scale experiments to
      manipulate temperature and CO2 concentration individually or in combination are
      thus urgently needed to examine their main and interactive effects on tropical
      forests. Such experiments will provide indispensable data and help gain essential
      knowledge on biogeochemical, hydrological and biophysical responses and feedbacks
      of tropical forests to climate change. These datasets can also inform regional
      and global models for predicting future states of tropical forests and climate
      systems. The success of such large-scale experiments in natural tropical forests
      will require an international framework to coordinate collaboration so as to meet
      the challenges in cost, technological infrastructure and scientific endeavor. 

PMID- 24128848
TI  - Intra-annual dynamics of non-structural carbohydrates in the cambium of mature
      conifer trees reflects radial growth demands.
AB  - The presence of soluble carbohydrates in the cambial zone, either from sugars
      recently produced during photosynthesis or from starch remobilized from storage
      organs, is necessary for radial tree growth. However, considerable uncertainties
      on carbohydrate dynamics and the consequences on tree productivity exist. This
      study aims to better understand the variation in different carbon pools at intra
      annual resolution by quantifying how cambial zone sugar and starch concentrations
      fluctuate over the season and in relation to cambial phenology. A comparison
      between two physiologically different species growing at the same site, i.e., the
      evergreen Picea abies Karst. and the deciduous Larix decidua Mill., and between
      L. decidua from two contrasting elevations, is presented to identify mechanisms
      of growth limitation. Results indicate that the annual cycle of sugar
      concentration within the cambial zone is coupled to the process of wood
      formation. The highest sugar concentration is observed when the number of cells
      in secondary wall formation and lignification stages is at a maximum, subsequent
      to most radial growth. Starch disappears in winter, while other freeze-resistant
      non-structural carbohydrates (NSCs) increase. Slight differences in NSC
      concentration between species are consistent with the differing climate
      sensitivity of the evergreen and deciduous species investigated. The general
      absence of differences between elevations suggests that the cambial activity of
      trees growing at the treeline was not limited by the availability of
      carbohydrates at the cambial zone but instead by environmental controls on the
      growing season duration. 

PMID- 24128849
TI  - Foraging strategies in trees of different root morphology: the role of root
      lifespan.
AB  - Resource exploitation of patches is influenced not simply by the rate of root
      production in the patches but also by the lifespan of the roots inhabiting the
      patches. We examined the effect of sustained localized nitrogen (N) fertilization
      on root lifespan in four tree species that varied widely in root morphology and
      presumed foraging strategy. The study was conducted in a 12-year-old common
      garden in central Pennsylvania using a combination of data from minirhizotron and
      root in-growth cores. The two fine-root tree species, Acer negundo L. and Populus
      tremuloides Michx., exhibited significant increases in root lifespan with local N
      fertilization; no significant responses were observed in the two coarse-root tree
      species, Sassafras albidum Nutt. and Liriodendron tulipifera L. Across species,
      coarse-root tree species had longer median root lifespan than fine-root tree
      species. Localized N fertilization did not significantly increase the N
      concentration or the respiration of the roots growing in the N-rich patch. Our
      results suggest that some plant species appear to regulate the lifespan of
      different portions of their root system to improve resource acquisition while
      other species do not. Our results are discussed in the context of different
      strategies of foraging of nutrient patches in species of different root
      morphology. 

PMID- 24128850
TI  - Inactive xylem can explain differences in calibration factors for thermal
      dissipation probe sap flow measurements.
AB  - Thermal dissipation probes (TDPs) were calibrated in three diffuse porous fruit
      trees and one ornamental species in the field by comparison with heat pulse
      probes (nectarine and persimmon), in a greenhouse on lysimeters (apple and
      persimmon) and in the laboratory by pushing water through cut branches (apple,
      Peltophorum and nectarine). Two operational methods were used: continuous
      (constant thermal dissipation, CTD) and discontinuous, or transient, heating
      (transient thermal dissipation, TTD). Correction for the radial distribution of
      sap flux density was with an analytical function derived from a linear decrease
      in flux density with depth, as measured with a multi-depth 'Tmax' heat pulse
      system. When analyzed with previous calibration factors, the measured sap flow
      was <50% of actual value. The underestimations were consistent, and calibrations
      for each species in the field, greenhouse and laboratory gave approximately the
      same factors. Reasonable values of tree water use were obtained with the new
      calibration factors. Evidence is provided that even though the xylem was diffuse
      porous, the underestimations were caused by contact of the probes with inactive
      xylem along their length. The average portion of probe in contact with inactive
      xylem, measured in stained branches following laboratory calibrations, was 0.2
      0.24. Using the measured fractions to correct temperature differentials between
      heated and unheated probes for CTD and TTD, based on Clearwater et al. (in
      Potential errors in measurement of nonuniform sap flow using heat dissipation
      probes. Tree Physiol 1999;19:681-687) almost completely compensated for the
      underestimations. Calibrations are given for each species both before and after
      corrections of temperature differentials, along with a multispecies calibration.
      These results should be an important step in reconciling many reports of
      different calibration factors for TDP probes. 

PMID- 24128851
TI  - Vortex beam production and contrast enhancement from a magnetic spiral phase
      plate.
AB  - Electron vortex beam probes offer the possibility of mapping magnetic moments
      with atomic resolution. In this work we consider using the stray magnetic field
      produced from a narrow ferromagnetic rod magnetised along its long axis to
      produce a vortex beam probe, as an alternative to the currently used holographic
      apertures or gratings. We show through numerical modelling, electron holography
      observations and direct imaging of the electron probe, that a long narrow
      ferromagnetic rod induces a phase shift in the wave-function of passing electrons
      that approximately describes a helix in the regions near its ends. Directing this
      rod towards the optical axis of a charged-particle beam probe forming system at a
      limiting aperture position, with the free-end sufficiently close to the axis, is
      shown to offer a point spread function composed of vortex modes, with evidence of
      this appearing in observations of the electron probe formed from inserting a
      micro-fabricated CoFe rod into the beam path of a 300 keV transmission electron
      microscope (TEM). If the rod is arranged to contain the magnetic flux of h/e,
      thus producing a maximum phase shift of 2pi, it produces a simple spiral-like
      phase contrast transfer function for weak phase objects. In this arrangement the
      ferromagnetic rod can be used as a phase plate, positioned at the objective
      aperture position of a TEM, yielding enhanced image contrast which is simulated
      to be intermediate between comparable Zernike and Hilbert phase plates. Though
      this aspect of the phase plate performance is not demonstrated here, agreement
      between our observations and models for the probe formed from an example rod
      containing a magnetic flux of ~2.35h/e, indicate this phase plate arrangement
      could be a simple means of enhancing contrast and gaining additional information
      from TEM imaged weak phase samples, while also offering the capability to produce
      vortex beam probes. However, steps still need to be taken to either remove or
      improve the support membrane for the rod in our experiments to reduce any effects
      from charging in the phase plate.

PMID- 24128852
TI  - Oxidative DNA damage and repair in children exposed to low levels of arsenic in
      utero and during early childhood: application of salivary and urinary biomarkers.
AB  - The present study aimed to assess arsenic exposure and its effect on oxidative
      DNA damage and repair in young children exposed in utero and continued to live in
      arsenic-contaminated areas. To address the need for biological specimens that can
      be acquired with minimal discomfort to children, we used non-invasive urinary and
      salivary-based assays for assessing arsenic exposure and early biological effects
      that have potentially serious health implications. Levels of arsenic in nails
      showed the greatest magnitude of difference between exposed and control groups,
      followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva
      showed significant positive correlations with other biomarkers of arsenic
      exposure, including arsenic accumulation in nails (r=0.56, P<0.001) and arsenic
      concentration in urine (r=0.50, P<0.05). Exposed children had a significant
      reduction in arsenic methylation capacity indicated by decreased primary
      methylation index and secondary methylation index in both urine and saliva
      samples. Levels of salivary 8-OHdG in exposed children were significantly higher
      (~4-fold, P<0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1
      expression were significantly lower in exposed children (~3-fold, P<0.05),
      suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG.
      Multiple regression analysis results showed that levels of inorganic arsenic
      (iAs) in saliva and urine had a significant positive association with salivary 8
      OHdG and a significant negative association with salivary hOGG1 expression. 

PMID- 24128853
TI  - CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor
      inhibition by reactive oxygen species and mitochondrial dysfunction.
AB  - Vitamin K3 derivatives have been shown to exert anticancer activities. Here we
      show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene
      1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition
      through reactive oxygen species (ROS) and mitochondrial dysfunction in human
      breast cancer. CR108 is more effective on the breast cancer cell death than other
      vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2
      overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108
      caused the loss of mitochondrial membrane potential, cytochrome c released from
      mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108
      markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a
      general ROS scavenger, completely blocked the CR108-induced ROS levels,
      mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the
      phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein
      expression. NAC treatment prevented the activation of p38 MAP kinase and rescued
      the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor,
      recovered the survivin protein levels and attenuated the cytotoxicity of CR108
      treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor
      growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3
      derivative that induces apoptosis and tumor inhibition by ROS production and
      mitochondrial dysfunction and associates with the phosphorylation of p38 MAP
      kinase and the inhibition of survivin in the human breast cancer. 

PMID- 24128854
TI  - Manipulation of the HIF-Vegf pathway rescues methyl tert-butyl ether (MTBE)
      induced vascular lesions.
AB  - Methyl tert-butyl ether (MTBE) has been shown to be specifically anti-angiogenic
      in piscine and mammalian model systems at concentrations that appear non-toxic in
      other organ systems. The mechanism by which MTBE targets developing vascular
      structures is unknown. A global transcriptome analysis of zebrafish embryos
      developmentally exposed to 0.00625-5mM MTBE suggested that hypoxia inducible
      factor (HIF)-regulated pathways were affected. HIF-driven angiogenesis via
      vascular endothelial growth factor (vegf) is essential to the developing
      vasculature of an embryo. Three rescue studies were designed to rescue MTBE
      induced vascular lesions: pooled blood in the common cardinal vein (CCV), cranial
      hemorrhages (CH), and abnormal intersegmental vessels (ISV), and test the
      hypothesis that MTBE toxicity was HIF-Vegf dependent. First, zebrafish vegf-a
      over-expression via plasmid injection, resulted in significantly fewer CH and ISV
      lesions, 46 and 35% respectively, in embryos exposed to 10mM MTBE. Then HIF
      degradation was inhibited in two ways. Chemical rescue by N-oxaloylglycine
      significantly reduced CCV and CH lesions by 30 and 32% in 10mM exposed embryos,
      and ISV lesions were reduced 24% in 5mM exposed zebrafish. Finally, a morpholino
      designed to knock-down ubiquitin associated von Hippel-Lindau protein,
      significantly reduced CCV lesions by 35% in 10mM exposed embryos. In addition,
      expression of some angiogenesis related genes altered by MTBE exposure were
      rescued. These studies demonstrated that MTBE vascular toxicity is mediated by a
      down regulation of HIF-Vegf driven angiogenesis. The selective toxicity of MTBE
      toward developing vasculature makes it a potentially useful chemical in the
      designing of new drugs or in elucidating roles for specific angiogenic proteins
      in future studies of vascular development. 

PMID- 24128855
TI  - Isoniazid suppresses antioxidant response element activities and impairs
      adipogenesis in mouse and human preadipocytes.
AB  - Transcriptional signaling through the antioxidant response element (ARE),
      orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major
      cellular defense mechanism against oxidative or electrophilic stress. Here, we
      reported that isoniazid (INH), a widely used antitubercular drug, displays a
      substantial inhibitory property against ARE activities in diverse mouse and human
      cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE
      luciferase reporter activity and mRNA expression of various ARE-dependent
      antioxidant genes under basal and oxidative stressed conditions. In keeping with
      our previous findings that Nrf2-ARE plays a critical role in adipogenesis by
      regulating expression of CCAAT/enhancer-binding protein beta (C/EBPbeta) and
      peroxisome proliferator-activated receptor gamma (PPARgamma), suppression of ARE
      signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human
      adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal
      cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced
      levels of lipid accumulation and attenuated expression of C/EBPalpha and
      PPARgamma. Time-course studies in 3T3-L1 cells revealed that inhibition of
      adipogenesis by INH occurred in the early stage of terminal adipogenic
      differentiation, where reduced expression of C/EBPbeta and C/EBPdelta was
      observed. To our knowledge, the present study is the first to demonstrate that
      INH suppresses ARE signaling and interrupts with the transcriptional network of
      adipogenesis, leading to impaired adipogenic differentiation. The inhibition of
      ARE signaling may be a potential underlying mechanism by which INH attenuates
      cellular antioxidant response contributing to various complications. 

PMID- 24128856
TI  - Expression of carbohydrate-antigen sialyl-Lewis a on colon cancer cells promotes
      xenograft growth and angiogenesis in nude mice.
AB  - We investigated the role of carbohydrate antigen sialyl-Lewis a (sLea), an E
      selectin ligand and epitope of tumor marker CA19.9, in the development of
      xenografts in nude mice. To this end, animals were inoculated with the human
      colon cancer cell line HCT-15, expressing no Lewis antigens, or with a clone
      expressing sLea (HCT-15-T5). The size of HCT-15-T5 xenografts appeared larger
      than those of HCT-15 and their average weight was over twice bigger. In both
      xenografts the mitotic index was found elevated, as determined by Ki-67 assay,
      and no apoptosis was detected in the tumor cells by both caspase 8 or TUNEL
      assays. Some apoptotic signals were instead detected in the vessels. Conversely,
      microvessel density, determined through CD-31 immunohistochemistry, was found 3.2
      folds bigger in HCT-15-T5 xenografts (p<0.012). Only the membranes of HCT-15-T5
      cells grown as xenografts reacted intensively with the anti CA19.9 antibody 1116
      NS-19-9 by immunofluorescence, but not by immunohistochemistry. Unknown
      structures were instead stained by such technique in both xenografts, as were in
      mouse tissues not expressing the antigen and in human colon adenocarcinoma. We
      conclude that expression of sLea on the surface of colon cancer cells improves
      xenograft growth and is associated with enhanced angiogenesis, while
      immunohistochemistry with 1116-NS-19-9 antibody appears not suitable to determine
      CA19.9 expression.

PMID- 24128857
TI  - Flavonoids as prospective compounds for anti-cancer therapy.
AB  - Flavonoids, which are polyphenolic compounds, are a class of plant secondary
      metabolites possessing a broad spectrum of pharmacological activity including
      anti-cancer activities. They have been reported to interfere in the initiation,
      promotion and progression of cancer by modulating different enzymes and receptors
      in signal transduction pathways related to cellular proliferation,
      differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal
      of multidrug resistance. Due to their multiple molecular mechanisms of action,
      flavonoids (both natural and synthetic analogs) are being investigated for their
      potential applications in anti-cancer therapies. In this review article, the main
      molecular mechanisms of action of flavonoids attributing to their potential anti
      cancer activities have been discussed and the key structural features required
      for their activity are highlighted. 

PMID- 24128858
TI  - The effect of coping knowledge on emergency preparedness in elementary school
      students.
AB  - The purpose of this study was to examine the effect of coping knowledge for
      emergency preparedness in Korean elementary school students. A school-based
      coping education program was provided seven times to 271 fourth- and fifth-grade
      students in two urban schools by researchers with the school nurses. The Process
      Model of Stress and Coping and Self-Care Deficit Theory were the theoretical
      frameworks used to guide this research. The Coping Knowledge for Emergency
      Situations Questionnaire, developed by the authors, was used to gather data. In
      the coping education group, there was statistically significant improvement in
      the coping knowledge (t = 4.589, p < .001) from that of the control group (n =
      270). The results highlight the importance of emergency preparedness for
      elementary school students and the need to develop educational programs for
      various emergency situations. 

PMID- 24128859
TI  - Influence of perceptions on school nurse practices to prevent childhood obesity.
AB  - Comprehensive childhood obesity prevention (COP) strategies should include
      increasing school nurse involvement. This study was conducted to determine the
      influence of key school nurse perceptions (self-efficacy, perceived benefits, and
      perceived barriers) on participation in COP practices at the individual child and
      school level. Florida registered nurse (RN) school nurses (n = 171) anonymously
      completed online or paper questionnaires. Linear regression analyses identified a
      model of self-efficacy with perceived benefits and barriers that explained 12%
      and 9.1% (p < .001) of variance in child-level and school-level COP practices,
      respectively. Self-efficacy explained the most variance in both models (p <
      .001). Mediation testing identified perceived barriers as a partial mediator of
      the influence of self-efficacy on child-level practices. These findings support
      interventions and policy changes to increase self-efficacy and reduce perceived
      barriers to promote school nurse involvement in preventing childhood obesity. 

PMID- 24128860
TI  - Activation of PPAR alpha and PPAR beta/delta regulates Sertoli cell metabolism.
AB  - The purpose of this study was to evaluate the existence of a possible
      simultaneous regulation of fatty acid (FA) metabolism and lactate production by
      PPAR alpha and PPAR beta/delta activation in Sertoli cells (SC). SC cultures
      obtained from 20-day-old rats were incubated with WY14643 or GW0742
      pharmacological activators of PPAR alpha and PPAR beta/delta respectively. The
      fatty acid transporter CD36, carnitine palmitoyltransferase 1, long- and medium
      chain 3-hydroxyacyl-CoA dehydrogenases mRNA levels were analyzed. An increase in
      the above-mentioned genes in response to activation of both nuclear receptors was
      observed. Additionally, PPAR beta/delta activation increased lactate production
      as a consequence of increased pyruvate availability by inhibiting the Pyruvate
      Dehydrogenase Complex. Altogether, these results suggest that in SC, PPAR alpha
      activation participates in the regulation of FA metabolism. On the other hand,
      PPAR beta/delta activation regulates FA metabolism and lactate production
      ensuring simultaneously the energetic metabolism for SC and germ cells. 

PMID- 24128861
TI  - CYP2B6*6 is an independent determinant of inferior response to fludarabine plus
      cyclophosphamide in chronic lymphocytic leukemia.
AB  - Fludarabine plus cyclophosphamide (FC) is the chemotherapy backbone of modern
      chronic lymphocytic leukemia (CLL) treatment. CYP2B6 is a polymorphic cytochrome
      P450 isoform that converts cyclophosphamide to its active form. This study
      investigated the possible impact of genetic variation in CYP2B6 on response to FC
      chemotherapy in CLL. Available DNA samples from the LRF CLL4 trial, which
      compared chlorambucil, fludarabine, and FC, were screened by TaqMan real-time
      polymerase chain reaction assays for CYP2B6 SNPs c.516G>T and c.785A>G, which
      define the most common variant allele (*6). Among the 455 samples successfully
      genotyped, 265 (58.2%), 134 (29.5%), and 29 (6.4%) were classified as *1/*1,
      *1/*6, and *6/*6, respectively. Patients expressing at least one *6 allele were
      significantly less likely to achieve a complete response (CR) after FC (odds
      ratio 0.27; P = .004) but not chlorambucil or fludarabine. Analysis of individual
      response indicators confirmed that this inferior response resulted from impaired
      cytoreduction rather than delayed hemopoietic recovery. Multivariate analysis
      controlling for age, gender, stage, IGHV mutational status, 11q deletion, and
      TP53 deletion/mutation identified CYP2B6*6 and TP53 mutation/deletion as the only
      independent determinants of CR attainment after FC. Our study provides the first
      demonstration that host pharmacogenetics can influence therapeutic response in
      CLL. This trial is registered as an International Standard Randomised Control
      Trial, number NCT 58585610 at www.clinicaltrials.gov. 

PMID- 24128862
TI  - The zebrafish granulocyte colony-stimulating factors (Gcsfs): 2 paralogous
      cytokines and their roles in hematopoietic development and maintenance.
AB  - Granulocyte colony-stimulating factor (Gcsf) drives the proliferation and
      differentiation of granulocytes, monocytes, and macrophages (mphis) from
      hematopoietic stem and progenitor cells (HSPCs). Analysis of the zebrafish genome
      indicates the presence of 2 Gcsf ligands, likely resulting from a duplication
      event in teleost evolution. Although Gcsfa and Gcsfb share low sequence
      conservation, they share significant similarity in their predicted
      ligand/receptor interaction sites and structure. Each ligand displays
      differential temporal expression patterns during embryogenesis and spatial
      expression patterns in adult animals. To determine the functions of each ligand,
      we performed loss- and gain-of-function experiments. Both ligands signal through
      the Gcsf receptor to expand primitive neutrophils and mphis, as well as
      definitive granulocytes. To further address their functions, we generated
      recombinant versions and tested them in clonal progenitor assays. These sensitive
      in vitro techniques indicated similar functional attributes in supporting HSPC
      growth and differentiation. Finally, in addition to supporting myeloid
      differentiation, zebrafish Gcsf is required for the specification and
      proliferation of hematopoietic stem cells, suggesting that Gcsf represents an
      ancestral cytokine responsible for the broad support of HSPCs. These findings may
      inform how hematopoietic cytokines evolved following the diversification of
      teleosts and mammals from a common ancestor.

PMID- 24128863
TI  - Age-Friendly Rural Communities: Conceptualizing 'Best-Fit'.
AB  - The literature on age-friendly communities is predominantly focused on a model of
      urban aging, thereby failing to reflect the diversity of rural communities. In
      this article, we address that gap by focusing on the concept of community in a
      rural context and asking what makes a good fi t between older people and their
      environment. We do this through (a) autobiographical and biographical accounts of
      two very different geographical living environments: bucolic and bypassed
      communities; and through (b) analysis of the different needs and resources of two
      groups of people: marginalized and community-active older adults, who live in
      those two different rural communities. We argue that the original 2007 Health
      Organization definition of age friendly should be reconceptualized to explicitly
      accommodate different community needs and resources, to be more inclusive as well
      as more interactive and dynamic, incorporating changes that have occurred over
      time in people and place.

PMID- 24128866
TI  - Hemispheric differences in blood pressures of patients with putaminal and
      thalamic hemorrhages.
AB  - Our assumption that blood pressure (BP) in supratentorial hypertensive
      intracerebral hemorrhage patients does not differ significantly according to the
      hemispheric laterality has never been verified before. This study was carried out
      to explore the possibility of hemispheric BP differences and whether this might
      influence the outcomes. A review of the charts/radiographic images of 281
      patients with putaminal/thalamic hemorrhages diagnosed within 6 h of symptom
      onset was performed. Immediately after arrival, they received a continuous
      intravenous nicardipine infusion to lower and maintain systolic BP (SBP) between
      120 and 160 mmHg. They were quadrichotomized as follows: left putamen (LP, n=89),
      right putamen (RP, n=69), left thalamus (LT, n=68), and right thalamus (RT,
      n=55). Two-group or four-group comparisons were made on demographic variables,
      BPs, and outcomes. Patients with left-sided hemorrhages presented with
      significantly worse neurologic scores in both hemorrhage categories and tended to
      sustain larger hematomas than their right-sided counterparts. Significant
      differences in SBPs between LP and RP (205 +/- 31 vs. 189 +/- 29 mmHg, P<0.01) as
      well as in diastolic BPs between LT and RT (109 +/- 19 vs. 97 +/- 20 mmHg,
      P=0.03) were noted. Multivariate regression analysis showed that patients with
      SBPs of at least 220 mmHg were 2.9 times more likely to harbor left-sided
      hemorrhages. There were no significant intergroup differences in responsiveness
      to a continuous intravenous nicardipine infusion or 30-day mortality rates.
      Although the differences in BPs are unlikely to have influenced outcomes, future
      trials involving supratentorial hypertensive intracerebral hemorrhages may
      benefit from considering hemispheric differences in BP and other demographic
      variables.

PMID- 24128867
TI  - Estradiol decreases rat depressive behavior by estrogen receptor beta but not
      alpha: no correlation with plasma corticosterone.
AB  - 17beta-Estradiol (E2) may influence some of the sex differences in stress-related
      neuropsychiatric disorders, such as anxiety and depression. E2 may also modulate
      the hypothalamic-pituitary-adrenal axis function as a cortisol response to stress
      in women. This study explored the role of E2 (10 and 50 MUg/rat) and selective
      estrogen receptor modulators: diarylpropionitrile (DPN, 10 MUg/rat) and propyl
      pyrazole triol (PPT, 10 MUg/rat), in anxiety and depressive behaviors in
      ovariectomized rats using an animal model. The study also examined the
      relationship between rats' affective behavior and the plasma corticosterone
      (CORT) levels in response to chronic repeated restraint stress and series of
      behavior tests. Ovariectomized rats administered 10 MUg E2 and 10 MUg DPN showed
      more central entries in the open field, more open-arm duration in the elevated
      plus maze, and less immobility duration in the forced-swim test compared with
      rats administered vehicle or 10 MUg PPT. 10 and 50 MUg E2 significantly increased
      plasma CORT levels when compared with vehicle, 10 MUg DPN, or 10 MUg PPT. There
      was no correlation between the rats' depressive behavior and their plasma CORT
      levels. These results suggest that the antidepressant effects of E2 may involve
      ERbeta, but are independent of an enhanced CORT response to stress. 

PMID- 24128868
TI  - Acetylcholine plays an antinociceptive role by modulating pain-induced discharges
      of pain-related neurons in the caudate putamen of rats.
AB  - The caudate putamen (CPu) has been suggested to be involved in nociceptive
      modulation. Some neurotransmitters, including acetylcholine (ACh), participate in
      pain modulation in the central nervous system. However, the active mechanism of
      ACh on the pain-related neurons in the CPu remains unclear. This study aimed to
      investigate the effects of the cholinergic agonists ACh and pilocarpine and the
      muscarinic ACh receptor antagonist atropine on the pain-induced response of pain
      related neurons in the CPu of Wistar rats. Trains of electrical impulses applied
      to the sciatic nerve of rat were used as the noxious stimulus. The electrical
      activities of pain-excited neurons (PENs) or pain-inhibited neurons (PINs) in the
      CPu were recorded by a glass microelectrode. Our results showed that an intra-CPu
      injection of 4 MUg/2 MUl ACh or pilocarpine decreased and increased the pain
      induced discharge frequency in the PENs and PINs, respectively. Intra-CPu
      administration of 1 MUg/2 MUl atropine produced the opposite effect on these
      neurons. These findings indicate that ACh may play an analgesic role by affecting
      the electric activities of PENs and PINs, and the muscarinic pathway may be
      involved in the modulation of pain perception in the CPu. 

PMID- 24128869
TI  - Antidepressive effect of sodium valproate involving suppression of corticotropin
      releasing factor expression and elevation of BDNF expression in rats exposed to
      chronic unpredicted stress.
AB  - Sodium valproate (VPA) is an antiepileptic drug and mood stabilizer used to treat
      bipolar disorders. Recently, other psychiatric uses for VPA have been based on
      its antidepressive and neuroprotective effects. In the current work, the
      antidepressive mechanism of VPA was investigated by studying the expression of
      brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal axis
      function in rats exposed to a protocol of chronic unpredicted stress (CUS). Male
      Sprague-Dawley rats were divided into a vehicle-treated control group (no
      CUS+vehicle), a VPA-treated control group (no CUS+VPA), a vehicle-treated model
      group (CUS+vehicle), and a VPA-treated model group (CUS+VPA). VPA (300 mg/kg once
      daily) was administered to rats (no CUS+VPA and CUS+VPA) by an intragastric
      gavage, whereas the same volume of vehicle was administered to rats in the no
      CUS+vehicle and CUS+vehicle groups. Rat behavior, serum corticosterone level, and
      expression of BDNF in the hippocampus and corticotrophin-releasing factor in the
      hypothalamus were determined. Compared with the CUS+vehicle rats, the CUS+VPA
      rats showed a significant relief in depression-like behaviors and a decrease in
      the corticosterone level and corticotropin-releasing factor expression with
      increasing expression of BDNF. The results suggest that the antidepressive effect
      of VPA is at least partly related to improving hypothalamic-pituitary-adrenal
      axis function and elevating the expression of BDNF. 

PMID- 24128870
TI  - Cognitive behavioral therapy for pediatric obsessive-compulsive disorder:
      development of expert-level competence and implications for dissemination.
AB  - Pediatric obsessive-compulsive disorder (OCD) is associated with substantial
      morbidity, comorbidity, family difficulties, and functional impairment.
      Fortunately, OCD in youth has also been found responsive to cognitive behavioral
      therapy (CBT) both alone and in combination with medication. This paper
      highlights key areas a treatment provider must be highly knowledgeable in to be
      considered an expert in cognitive behavioral therapy (CBT) for pediatric
      obsessive-compulsive disorder (OCD). We describe the areas of knowledge that must
      be mastered to gain expertise, as well as the more difficult to quantify personal
      qualities that may allow a clinician to convey this knowledge in an expert
      manner. We provide detailed discussions of CBT theory, assessment strategies,
      implications of the treatment outcome literature for clinical decision-making,
      and how best to navigate CBT. We also discuss what the expert needs to accomplish
      by engaging youth and families throughout the evaluation and treatment process. 

PMID- 24128871
TI  - Leishmania infantum (Trypanosomatida: Trypanosomatidae) phlebotomine sand fly
      vectors in continental Mediterranean Spain.
AB  - Leishmania infantum-the causal agent of human and canine leishmaniasis in the
      Mediterranean basin-remains the most important of the phlebotomine sand fly-borne
      pathogens in the area. However, information on phlebotomine sand flies in certain
      European regions remains scarce and consequently epidemiological modeling, risk
      prediction, and disease control are difficult. Thus, we aimed to investigate the
      presence and distribution of phlebotomine sand fly vectors of L. infantum in an
      endemic region of continental Mediterranean Spain. Climatically stratified
      trapping of phlebotomine sand flies was performed over 39 points in south-central
      Spain. Later on, the effect of ecogeographical variables-geography trend,
      climate, habitat, and hosts-over the abundance of the predominant species
      Phlebotomus perniciosus Newstead, 1911-was analyzed. Polymerase chain reaction
      was performed over pools of the captured species to search for L. infantum DNA.
      There were 152 phlebotomine sand flies (142 Ph. perniciosus and 10 Phlebotomus
      ariasi Tonnoir, 1921) captured. Model results showed that Ph. perniciosus
      abundance is expected to be higher in warm agricultural areas within the study
      region in agreement to previous findings in other climatic regions. Molecular
      analyses revealed the presence of L. infantum DNA in pools from locations in the
      study region displaying the highest abundance of phlebotomine sand flies. These
      findings suggest that along mainland Spain, warm agricultural landscapes are more
      prone to harbor higher abundances of Ph. perniciosus and account for a higher
      risk of exposure to L. infantum. 

PMID- 24128872
TI  - Reference range and short- and long-term biological variation of interleukin (IL)
      6, IL-17A and tissue necrosis factor-alpha using high sensitivity assays.
AB  - Interleukin (IL)-6, and tissue necrosis factor alpha (TNF-alpha) are established
      biomarkers for clinical practice and use in clinical trials of patients with
      cardiovascular disease. IL-17A may be an emerging marker for atherosclerosis
      disease progression. We measured IL-6, TNF-alpha, and IL-17A using a high
      sensitivity immunoassay (Erenna, Singulex, Inc.) to determine the reference range
      and to calculate the weekly (25 subjects over 6weeks) and monthly (17 subjects
      over 9months) biological variation (BV) from apparently healthy subjects and
      those attending a cardiovascular disease clinic. As a validation for the
      experimental and statistical approach taken, the weekly BV for high sensitivity C
      reactive protein was also determined and result compared to previous reports. The
      upper 95th percentile reference limit for IL-6, TNF-alpha, and IL17-A was 4.45,
      2.53, and 1.93pg/mL, respectively. The intra-individual variability ranged from
      21% to 57% and the inter-individual variation ranged from 22% to 53%. The
      corresponding index of individuality was 0.65-1.6 and reference change values
      from 63% to 161%. The BV for IL-6 and TNF-alpha are similar to previous reports,
      documenting their diagnostic utility in clinical practice. Up until now, the
      biological variation of IL-17A and upper reference limit has not been previously
      reported, thereby limiting the use of this marker in clinical trials. 

PMID- 24128873
TI  - The separation of monocular and binocular contrast.
AB  - The contrast asynchrony is a stimulus configuration that illustrates the visual
      system's separable responses to luminance and luminance contrast information
      (Shapiro, 2008; Shapiro et al., 2004). When two disks, whose luminances modulate
      in phase with each other, are each surrounded by a disk, one light and one dark,
      observers can see both the in-phase brightness signals and the antiphase contrast
      signals and can separate the two. Here we present the results of experiments in
      which observers viewed a similar stimulus dichoptically. We report that no
      asynchrony is perceived when one eye is presented with modulating disks and the
      other eye is presented with the black and white surround rings, nor is an
      asynchrony perceived in gradient versions of the contrast asynchrony. We also
      explore the "window shade illusion" (Shapiro, Charles, & Shear-Heyman, 2005)
      dichoptically and find that when a modulating disk is presented to one eye and a
      horizontally split black/white annulus is presented to the other, observers
      perceive a "shading" motion up and down the disk. This shading can be seen in
      either direction in the binocular condition, but it is almost always seen as
      moving towards low contrast in the monocular condition. These findings indicate
      the presence of separable retinal and cortical networks for contrast processing
      at different temporal and spatial scales. 

PMID- 24128874
TI  - Pulmonary artery pseudoaneurysm caused by Streptococcus constellatus.
AB  - We report a rare case of mycotic pulmonary artery pseudoaneurysm (PAP) secondary
      to a lung abscess due to Streptococcus constellatus. PAP was confirmed by the
      pathological findings of the pseudoaneurysm, the presence of bacteria, and the
      microbiological analysis. PAP is uncommon, but it is important to recognize this
      condition because PAP can lead to fatal hemoptysis. 

PMID- 24128876
TI  - Studies on the potential and public health importance of non-biting synanthropic
      flies in the mechanical transmission of human enterohelminths.
AB  - BACKGROUND: This study was aimed at examining the potential of non-biting
      synanthropic filth flies to acquire naturally eggs of human intestinal helminths
      from unsanitary sites, and its attendant public health importance. METHODS: Body
      surface washings and gut contents of flies caught foraging while infected human
      faeces lay exposed at a garbage dump in Iperu, Ogun State, Nigeria and within 24
      hours subsequently after removal of faeces from the dump were examined
      parasitologically by the formol-ether concentration technique. The viability of
      helminth eggs isolated from flies was determined by incubation under laboratory
      conditions. RESULTS: A total of 303 flies were examined: Musca domestica (107;
      35.3%), Chrysomya megacephala (125; 41.3%) and Musca sorbens (71; 23.4%). Eggs of
      Ascaris lumbricoides and Trichuris trichiura isolated from exposed human faeces
      were recovered from the body surfaces and or gut contents of flies caught before
      (141; 77.5%) and after removal of exposed faeces (44; 36.4%). Eggs of Taenia sp.
      were isolated only from the gut contents of three C. megacephala flies caught
      after removal of exposed faeces. Significantly more (p<0.05) eggs were recovered
      from fly gut contents than body surfaces and from flies caught before than after
      removal of exposed faeces. 93.1% (552; from exposed faeces) and 57.4% (408; from
      flies) of A. lumbricoides and T. trichiura eggs were viable. CONCLUSIONS:
      Synanthropic flies may, because they carry viable eggs acquired naturally from
      unsanitary sites, be involved in the epidemiology of human intestinal
      helminthiases.

PMID- 24128875
TI  - Virulence of infecting Helicobacter pylori strains and intensity of mononuclear
      cell infiltration are associated with levels of DNA hypermethylation in gastric
      mucosae.
AB  - DNA methylation changes are known to occur in gastric cancers and in premalignant
      lesions of the gastric mucosae. In order to examine variables associated with
      methylation levels, we quantitatively evaluated DNA methylation in tumors, non
      tumor gastric mucosae, and in gastric biopsies at promoters of 5 genes with
      methylation alterations that discriminate gastric cancers from non-tumor
      epithelia (EN1, PCDH10, RSPO2, ZIC1, and ZNF610). Among Colombian subjects at
      high and low risk for gastric cancer, biopsies from subjects from the high-risk
      region had significantly higher levels of methylation at these 5 genes than
      samples from subjects in the low risk region (p <= 0.003). When results were
      stratified by Helicobacter pylori infection status, infection with a cagA
      positive, vacA s1m1 strain was significantly associated with highest methylation
      levels, compared with other strains (p = 0.024 to 0.001). More severe gastric
      inflammation and more advanced precancerous lesions were also associated with
      higher levels of DNA methylation (p <= 0.001). In a multivariate model, location
      of residence of the subject and the presence of cagA and vacA s1m1 in the H.
      pylori strain were independent variables associated with higher methylation in
      all 5 genes. High levels of mononuclear cell infiltration were significantly
      related to methylation in PCDH10, RSPO2, and ZIC1 genes. These results indicate
      that for these genes, levels of methylation in precancerous lesions are related
      to H. pylori virulence, geographic region and measures of chronic inflammation.
      These genes seem predisposed to sustain significant quantitative changes in DNA
      methylation at early stages of the gastric precancerous process. 

PMID- 24128877
TI  - Assessment of cystatin C and cystatin C-based GFR formulas in reflux nephropathy.
AB  - OBJECTIVE: Early identification of reflux nephropathy (RN) could reduce the
      frequency of chronic kidney disease (CKD) caused by vesicoureteral reflux (VUR).
      We aimed to assess whether cystatin C has value for determining RN in children
      with VUR. MATERIALS AND METHODS: Ninety-three children with VUR were classified
      into two groups according to the presence of renal parenchymal scarring (RS).
      Patients with RS were divided into three subgroups according to scar grade. Serum
      cystatin C, serum creatinine (Scr) and urine creatinine were measured. eGFR
      values of the patients were calculated with Scr-based, cystatin C-based and
      combined formulas. RESULTS: Cystatin C was significantly higher in patients with
      RS than patients without RS and declined in parallel with grade of RS (p = 0.01).
      Scr was not significant in patients with and without RS. It was only significant
      between mild and severe scar subgroups (p < 0.05). All eGFR values were lower in
      RS (+) patients compared with RS (-) patients. All eGFR equations were negatively
      correlated with grade of RS (p < 0.05). CONCLUSION: Cystatin C could be a useful
      marker for identifying the risk and severity of RN in patients with VUR. Renal
      functions could be more accurately determined with Scr-cystatin C combined eGFR
      equations.

PMID- 24128878
TI  - Comparison of magnetic resonance urography to dimercaptosuccinic acid scan for
      the identification of renal parenchyma defects in children with vesicoureteral
      reflux.
AB  - OBJECTIVE: The objective of this study was to compare the accuracy of
      dimercaptosuccinic acid (DMSA) renal scan to magnetic resonance urography (MRU)
      in the identification of renal parenchyma defects (RPD). MATERIALS AND METHODS:
      Twenty-five children with history of acute pyelonephritis and vesicoureteral
      reflux underwent DMSA scan and MRU to determine the presence of RPD. DMSA scans
      and MRUs were each evaluated by two radiologists and agreement achieved by
      consensus. Discordant DMSA-MRU findings were re-evaluated in a side-by-side
      comparison and an ultimate consensus reached. RESULTS: The ultimate consensus
      diagnosis was 18 kidneys with RPDs in 15 patients, of which five were classified
      as mild RPDs, six as moderate RPDs, and seven as severe RPDs. Although DMSA scan
      and MRU were similar in their ability to diagnose RPDs, MRU was considered to
      represent the true diagnosis in 11 of the 12 discordant cases in consensus review
      by four pediatric radiologists. MRU showed a much higher inter-observer agreement
      with a weighted kappa of 0.96 for both kidneys compared to 0.71 for the right
      kidney and 0.86 for the left kidney by DMSA scan. CONCLUSIONS: Our results
      suggest that MRU is superior to DMSA scan in the identification of renal
      parenchyma defects.

PMID- 24128879
TI  - Age-related decline in attentional shifting: Evidence from ERPs.
AB  - The present study investigated age-related attentional changes by comparing event
      related potentials (ERPs) in young and older adults during a rapid serial visual
      presentation task. We focused on analyzing the P3a and the N2 in both the target
      stimulus and the immediately succeeding irrelevant stimulus. As compared with
      younger adults, older adults exhibited a marked reduction in the amplitude of the
      P3a and N2 elicited by the stimulus following the target stimulus. Moreover, in
      younger adults, the P3a and N2 amplitudes did not differ between both stimuli,
      whereas in older adults these ERP components were significantly reduced in the
      subsequent stimulus compared to the target one. The age-related attenuation of
      P3a and N2 amplitudes for the subsequent stimulus indicates that older adults
      take longer and have more difficulty shifting their attention from one stimulus
      to the next one. 

PMID- 24128880
TI  - Astrocyte loss and astrogliosis in neuroinflammatory disorders.
AB  - Neuroinflammation can lead to either damage of astrocytes or astrogliosis.
      Astrocyte loss may be caused by cytotoxic T cells as seen in Rasmussen
      encephalitis, auto-antibodies such as in neuromyelitis optica (aquaporin-4
      antibodies), or cytokines such as TNF-alpha in major depressive disorder.
      Interleukins-1 and -6 appear to be important molecular mediators of astrogliosis.
      Chronic focal lesions in multiple sclerosis are characterized by a very dense
      astrogliosis. Other mechanisms, such as astrocytic beta2 adrenergic receptor
      deficiency, upregulation of endothelin-1 and tissue transglutaminase, may
      contribute to astroglial scarring in multiple sclerosis. 

PMID- 24128881
TI  - Morphine sensitivity of spinal neurons in the chronic constriction injury
      neuropathic rat pain model.
AB  - Opioid analgesia involves suppression of neuronal activity in central sensory
      pathways. We show that the classic opioid morphine reduces spinal neuronal
      spontaneous and evoked activity after induction of neuropathy by chronic
      constriction injury of the sciatic nerve in rats. The minimal effective dose of
      morphine was 0.3 mg/kg for most response parameters tested. Morphine sensitivity
      of spinal cord neurons is similar across neuropathic pain models. We therefore
      conclude that nerve damage per se rather than the experimental model determines
      the effectiveness of opioids in general and investigate several pain measurement
      endpoints which might be important to clinically determine morphine's efficacy in
      neuropathic pain.

PMID- 24128882
TI  - Lhermitte-Duclos disease with obstructive hydrocephalus: An illustrative case
      treated with endoscopic ventriculo-cisternostomy.

PMID- 24128884
TI  - Reprint of 'Age-related changes in executive control and their relationships with
      activity performance in handwriting'.
AB  - Deterioration in the frontal and prefrontal cortex associated with executive
      functions (EF) occurs with age and may be associated with changes in daily
      performance. The aim of the present study was to describe changes occurring with
      age in Executive Functions (EF) and handwriting activity, as well as to analyze
      relationships between age, EF and handwriting performance. The study population
      included 80 healthy participants (aged 31 to 76+) living in the community. After
      answering five questions about their writing habits, the participants completed
      the Behavioral Assessment of the Dysexecutive Syndrome (BADS). In addition, they
      performed a handwriting task on a digitizer included in the Computerized
      Penmanship Evaluation Tool (ComPET), which provides kinematic measures of the
      handwriting process. Significant differences were found between the four age
      groups for both EF and temporal and spatial handwriting measures. A series of
      regressions indicated that age predicted 35% of the variance of the BADS profile
      score (EF control) and 32% of the variance of in-air time while writing. The
      results of this study indicated age effect on both EF control and handwriting
      performance. Possible implications for further research and clinical evaluation
      and intervention are discussed.

PMID- 24128883
TI  - Reprint of 'Development, maturation and learning influence on handwriting
      kinematics'.
AB  - Handwriting is the result of a process in which linguistic, psychomotor and
      biomechanical factors interact with physical maturation, cognitive development
      and learning. Digital tablets, which record the writing in real time, allow a
      kinematic analysis of written trace: the implemented algorithms analyze
      parameters as length, duration and speed of the components (trace between two pen
      lifts) and strokes (trace between two minima of curvilinear velocity). The
      purpose of this work is to fill, at least for Italy, the lack of normative data
      on typical handwriting processes. This cross-sectional study will present data on
      218 right-handed and Italian mother-tongue students, attending classes from 2nd
      to 8th grade. They performed specific tasks (tests of writing speed;
      transcription of a sentence accurately vs. speedily) by a digital tablet. The
      analysis showed many changes of the considered parameters across the classes, as
      in the horizontal, curvilinear mean and peak velocities of components and
      strokes, with higher values in the last years of schooling and a parallel
      decrease in the number of strokes/letter (improvement of automation). In
      conclusion, some of these parameters are useful for studying development and
      learning of writing and their values can be used as references to evaluate
      samples with different characteristics.

PMID- 24128885
TI  - Interpreting cardiac troponin results from highly sensitive assays in patients
      with chronic kidney disease: acute coronary syndromes and beyond.
AB  - Cardiac troponin assays have become an indispensable tool in the diagnosis of
      acute myocardial infarction (MI). However, asymptomatic patients with chronic
      kidney disease often exhibit elevated levels of cardiac troponins with near
      ubiquitous detection using the new high-sensitive assays. This poses a challenge
      to physicians faced with differentiating between acute MI and a noncardiac
      etiology of chest pain or equivalent. Rather than rely on absolute cutoffs it is
      necessary to follow trends in levels at least over several hours. Even in the
      absence of an acute MI there is an association between chronic elevations of
      these biomarkers, underlying structural heart disease and poor prognosis.
      Although in the chronic setting the underlying cause of cardiac troponin
      elevation is likely a combination of factors, it should prompt further
      investigation for modifiable risk factors. 

PMID- 24128886
TI  - Will high-sensitivity troponin assays lead to improved outcomes in patients with
      acute coronary syndrome?
AB  - New high-sensitivity cardiac troponin (hs-cTn) assays have been developed that
      can measure troponin values at much lower levels. How these new assays should be
      integrated into clinical practice is an area of active discussion and research.
      This review addresses how the identification of more high-risk patients with
      acute coronary syndrome may improve clinical outcomes in these patients. With the
      advent of the new hs-cTn assays, more patients with unstable angina will be
      classified as having non-ST-elevation myocardial infarction. These assays will
      define a high-risk patient population that was not possible with older generation
      assays. One study suggests that this will lead to more appropriate therapy in
      these patients and improved outcomes. The use of hs-cTn assays will identify more
      high-risk patients among millions of patients who present to the Emergency
      Departments each year with undifferentiated chest pain. This will likely
      translate into more appropriate care and improved outcomes in this difficult
      patient population when ECG findings and clinical presentation do not suggest a
      clear diagnosis. 

PMID- 24128887
TI  - Comparison of mortality in patients with coronary or peripheral artery disease
      following the first vascular intervention.
AB  - OBJECTIVES: Patients with peripheral artery disease (PAD) less frequently achieve
      secondary prevention goals compared with patients with coronary artery disease
      (CAD). We aimed to compare mortality rates in patients with PAD and CAD following
      first vascular intervention. PATIENTS AND METHODS: Patients 18 years of age or
      older without a history of cardiovascular disease, who underwent first coronary
      or lower limb vascular intervention between 2002 and 2010, were included in this
      study. The primary endpoint was all-cause mortality. RESULTS: Of the 9950
      participants, 8242 (82.8%) underwent first coronary revascularization and 1708
      (17.2%) received first peripheral vascular intervention. During a mean follow-up
      period of 5.6+/-2.3 years, 1283 (12.9%) participants died. Compared with CAD
      patients, patients with PAD had significantly worse long-term prognosis with an
      increased risk for all-cause mortality (hazard ratio=2.95, 95% confidence
      interval 2.6-3.3, P<0.0001). This association remained statistically significant
      following a multivariable analysis (hazard ratio=1.86, 95% confidence interval
      1.6-2.1, P<0.0001). Furthermore, PAD patients were less frequently treated with
      cardioprotective medications including statins, angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, aspirin, and clopidogrel (P<0.001).
      CONCLUSION: Patients with PAD have worse outcome compared with patients with CAD,
      even in the specific group of patients following first vascular intervention.
      These findings demand more effort to improve secondary prevention guidelines in
      all patients with cardiovascular diseases, but especially in PAD patients.

PMID- 24128888
TI  - High-sensitive cardiac troponin assays: more information, more challenges.

PMID- 24128889
TI  - Eicosapentaenoic acid is converted via omega-3 epoxygenation to the anti
      inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid.
AB  - Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory
      disorders. In this study, dietary EPA was converted to 17,18
      epoxyeicosatetraenoic acid (17,18-EpETE) by omega-3 epoxygenation in the mouse
      peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated
      metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18
      epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti
      inflammatory action by limiting neutrophil infiltration in murine zymosan-induced
      peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B4-induced neutrophil
      chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The
      complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE
      and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These
      natural isomers displayed potent anti-inflammatory action, whereas the unnatural
      stereoisomers were essentially devoid of activity. These results demonstrate that
      17,18-EpETE derived from dietary EPA is converted to a potent bioactive
      metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory
      metabolic pathway.

PMID- 24128890
TI  - Transcriptional control of the B3GALT5 gene by a retroviral promoter and
      methylation of distant regulatory elements.
AB  - We focused on transcription factors and epigenetic marks that regulate the
      B3GALT5 gene through its retroviral long terminal repeat (LTR) promoter. We
      compared the expression levels of the B3GALT5 LTR transcript, quantitated by
      competitive RT-PCR, with those of the candidate transcription factors
      HNF1alpha/beta and Cdx1/2, determined by Western blot analysis, in colon cancer
      biopsies, various cell lines, and cell models serving as controls. We found that
      HNF1alpha/beta were easily detected, irrespective of the amount of LTR transcript
      expressed by the source, whereas Cdx1/2 were undetectable, and no sample lacking
      HNF1alpha/beta expressed the LTR transcript. On transfection in proper host
      cells, both HNF1alpha and HNF1beta provided detectable LTR transcript, whereas
      shRNA-mediated silencing of HNF1beta impaired transcription. Treating cells with
      5'-aza-2'-deoxycytidine (5AZA) strongly reduced expression, without affecting
      HNF1alpha/beta, despite the lack of CpG islands in the LTR and proximal
      sequences. By electrophoresis mobility shift and luciferase reporter assays, the
      LTR promoter binding and activity did not correlate with the amounts of LTR
      transcript expressed in the cells and depended on the levels of the transcription
      factors. We conclude that HNF1alpha/beta are necessary but insufficient to
      activate and regulate B3GALT5 LTR transcription, which depends on unknown
      regulatory elements that are active when methylated and located outside of and
      far from the LTR promoter.

PMID- 24128891
TI  - Dynamics of Schmallenberg virus infection within a cattle herd in Germany, 2011.
AB  - In late 2011, the insect-transmitted Schmallenberg virus (SBV) emerged in Europe.
      In this study, a cattle farm located in the core region of the epidemic was
      closely monitored between May 2011 and January 2012. Up to the end of September
      every tested serum sample was negative by an SBV-specific antibody ELISA,
      suggesting the absence of an infection before autumn 2011. Around the end of
      September/beginning of October SBV genome was detected in blood samples of some
      animals, and a few cows exhibited fever during that period. Starting at the end
      of September the first cows seroconverted; the within-herd prevalence reached
      100% within barely 1 month. Consequently, SBV spread rapidly in the tested herd
      during the vector season of 2011.

PMID- 24128892
TI  - Morphologic evaluation of the fetal recurrent laryngeal nerve and motor units in
      the thyroarytenoid muscle.
AB  - This study is a morphologic description of the recurrent laryngeal nerve (RLN)
      and of the number and size of motor units (MUs) in the thyroarytenoid (TA) muscle
      bilaterally of a human fetus aged 25 weeks. A quantitative analysis of RLN and
      MUs is presented to investigate similarities with equivalent structures in
      adults. In the fetus used in our study, the morphologic organization of the RLN
      was similar to that commonly described in the adult RLN. Moreover, as is observed
      in adult TA, the TA of the analyzed fetus, particularly the right TA, showed MUs
      typical of muscles with great motor accuracy. These results may be used to
      increase our knowledge of the features of the voice in adults and newborns. 

PMID- 24128893
TI  - Degrees of dysplasia based on viral typing in patients with cidofovir use and
      recurrent respiratory papillomatosis.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the degree of dysplasia following cidofovir
      injections while documenting human papillomavirus (HPV) type in patients with
      recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart
      review. METHODS: Demographic data, operative reports, and pathology results were
      reviewed from 25 patients with RRP who had had cidofovir injections. All patients
      included had adult onset RRP, no history of immunosuppression, well-controlled
      laryngopharyngeal reflux, and no current smoking history. Eight patients were
      excluded because they did not meet the inclusion criteria. RESULTS: Seventeen
      patients had adequate data for analysis and 40 subsites were identified with
      sufficient data for analysis. Patients negative for both low and high risk did
      not have progressive dysplasia at the conclusion of the study. Of the patients
      with positive viral typing, 70% had progressive disease at the conclusion of the
      study. No patients progressed to carcinoma or carcinoma in situ. The average pre-
      and post-treatment dysplasia scores were analyzed using a Student paired t test.
      There was no difference in mean dysplasia score, indicating that there was no
      increased risk of dysplasia following cidofovir treatment. CONCLUSIONS: To our
      knowledge, this is the first study looking at the degree of dysplasia while
      documenting HPV types in RRP. Our study suggests that HPV type appears to be
      relevant in the disease progression of RRP and that cidofovir does not increase
      the risk of dysplasia.

PMID- 24128894
TI  - Correlation between the basic video laryngostroboscopic parameters and
      multidimensional voice measurements.
AB  - OBJECTIVE: The aim of this study is to evaluate the correlations among the basic
      video laryngostroboscopic (VLS) parameters and vocal function assessed using a
      multidimensional set of perceptive, acoustic, aerodynamic, and subjective
      measurements. METHODS: Digital VLS recordings and multidimensional voice
      assessment were performed for 108 individuals, namely 26 healthy and 82 patients
      with mass lesions of vocal folds and paralysis. The VLS variables (glottal
      closure, regularity, mucosal wave on the affected/healthy side, symmetry of
      vibration, and symmetry of image) were rated and quantified on a visual analog
      scale. Correlations among the VLS parameters and results of acoustic voice
      analysis and voice range profile (VRP), data of subjective (voice handicap index
      [VHI] and glottal function index [GFI]), perceptual (G-grade, R-roughness, B
      breathiness, A-asthenic scale), and dysphonia severity index (DSI) measurements
      were tested using Pearson's correlation coefficient. RESULTS: The
      intercorrelations of VLS parameters in vocal performance were moderate to strong
      and statistically significant for the entire functional measurements obtained
      through different modalities. The definitive correlations between VLS and VRP
      parameters were as follows: r=0.69-0.79 for normal profile coverage, r=0.67-0.76
      for dynamic intensity, and r=0.67-0.74 for maximum intensity. All VLS parameters
      correlated moderately with VHI, GFI, and DSI (r=0.5-0.65, r=0.4-0.57, and r=0.61
      0.69, respectively). The strongest correlations were found between VLS parameters
      and G factor of the GRBA scale (r=0.68-0.88). CONCLUSIONS: Correlation analysis
      of the vibratory pattern of the vocal folds obtained via VLS provides more
      comprehensive insight into the pathophysiology of phonation and suggests the
      documented and measurable evidence of complex mechanisms of vocal outcome.

PMID- 24128896
TI  - Voxel-based dual-time 18F-FDG parametric imaging for rectal cancer:
      differentiation of residual tumor from postchemoradiotherapy changes.
AB  - INTRODUCTION: 18F-Fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) has
      been used for evaluation of the response of rectal cancer to neoadjuvant
      chemoradiotherapy (CRT), but differentiating residual tumor from post-treatment
      changes remains a problem. We propose a voxel-based dual-time 18F-FDG PET
      parametric imaging technique for the evaluation of residual rectal cancer after
      CRT. MATERIALS AND METHODS: Eighty-six patients with locally advanced rectal
      cancer who underwent neoadjuvant CRT between March 2009 and February 2011 were
      selected retrospectively. Standard 60-min postinjection PET/CT scans followed by
      90-min delayed images were coregistered by rigid-body transformation. A dual-time
      parametric image was generated, which divided delayed standardized uptake value
      (SUV) by 60-min SUV on a voxel-by-voxel basis. Maximum delayed-to-standard SUV
      ratios (DSR) measured on the parametric images as well as the percentage of SUV
      decrease from pre-CRT to post-CRT scans (pre/post-CRT response index) were
      obtained for each tumor and correlated with pathologic response classified by the
      Dworak tumor regression grade (TRG). RESULTS: With respect to the false-positive
      lesions in the nine post-CRT patients with false-positive standard 18F-FDG scans
      in case groups who responded to therapy (TRG 3 or 4 tumors), eight were
      undetectable on dual-time parametric images (P<0.05). The maximum DSR showed
      significantly higher accuracy for identification of tumor regression compared
      with the pre/post-CRT response index in receiver-operating characteristic
      analysis (P<0.01). With a 1.25 cutoff value for the maximum DSR, 85.0%
      sensitivity, 95.5% specificity, and 93.0% overall accuracy were obtained for
      identification of good response. CONCLUSION: A voxel-based dual-time parametric
      imaging technique for evaluation of post-CRT rectal cancer holds promise for
      differentiating residual tumor from treatment-related nonspecific 18F-FDG uptake.

PMID- 24128895
TI  - Prior TLR5 induction in human T cells results in a transient potentiation of
      subsequent TCR-induced cytokine production.
AB  - Activation of TLRs by components required for pathogen viability results in
      increased inflammation and an enhanced immune response to infection. Unlike their
      effects on other immune cells, TLR activation in the absence of T cell antigen
      receptor (TCR) induction has little effect on T cell activity. Instead, the
      simultaneous induction of TLR and TCR results in increased cytokine release
      compared to TCR treatment alone. Thus, the current model states that TLRs alter T
      cell function only if activated at the same time as the TCR. In this study, we
      tested the novel hypothesis that prior TLR induction can also alter TCR-mediated
      functions. We found that human T cells responded to ligands for TLR2 and TLR5.
      However, only prior TLR5 induction potentiated subsequent TCR-mediated cytokine
      production in human T cells. This response required at least 24h of TLR5
      induction and lasted for approximately 24-36h after removal of a TLR5 ligand.
      Interestingly, prior TLR5 induction enhanced TCR-mediated activation of Akt
      without increasing Lck, LAT or ERK kinase phosphorylation. Together, our studies
      show that TLR5 induction leads to a transient increase in the sensitivity of T
      cells to TCR stimulation by selectively enhancing TCR-mediated Akt function,
      highlighting that timeframe when TLR5 can potentiate TCR-induced downstream
      functions are significantly longer that previously appreciated.

PMID- 24128897
TI  - SPECT/CT localization of oral radioiodine activity: a retrospective study and in
      vitro assessment.
AB  - PURPOSE: We sought to further localize radioiodine activity in the mouth on post
      thyroid cancer therapy imaging using single-photon emission computed
      tomography/computed tomography (SPECT/CT). MATERIALS AND METHODS: We
      retrospectively reviewed all patients (58) who underwent thyroid cancer therapy
      with iodine-131 (131I) at our institution from August 2009 to March 2011 whose
      post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of
      diagnostic 131I scans including SPECT/CT was also reviewed. Separately, we
      performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco
      HP 77 (77% dental gold alloy) as proof of principle for these interactions.
      RESULTS: Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental
      restorations, and of them 41 (91%) demonstrated oral 131I activity localizing
      preferentially to those restorations. It was observed that radioiodine also
      localized to other dental restorations and to orthodontic hardware. Gum-line
      activity in edentulous patients suggests radioiodine interaction with denture
      adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time
      dependent manner over 1-16 days of exposure. Despite subsequent washings with
      normal saline, significant 131I activity (maximally 12% for amalgam and 68% for
      Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated
      solution of potassium iodide partially displaced 131I from amalgam, with near
      total displacement of I from Argenco HP 77. CONCLUSION: SPECT/CT shows that
      radioiodine in the oral cavity localizes to metallic dental restorations.
      Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to
      common dental metals.

PMID- 24128898
TI  - Technetium-99m methoxyisobutylisonitrile scintigraphy in the assessment of cold
      thyroid nodules: is it time to change the approach to the management of cold
      thyroid nodules?
AB  - BACKGROUND: Scanning with technetium-99m methoxyisobutylisonitrile (Tc-MIBI) is
      recommended for evaluating thyroid nodule metabolism. In addition, it may help
      differentiate between benign and malignant nodules; however, the efficacy of this
      technique has not been fully elucidated. Therefore, it is not currently performed
      for routine clinical application. This prospective study was conducted to
      investigate the clinical significance of Tc-MIBI scintigraphy in the assessment
      of patients with cold thyroid nodules. PATIENTS AND METHODS: This prospective
      study was conducted on 104 patients with cold thyroid nodules greater than 1 cm
      in diameter as detected on Tc-pertechnetate scintigraphy. Uptake of MIBI in
      thyroid nodules was compared with that in the surrounding normal thyroid tissue
      for both early and delayed images, and a score of 0-3 was assigned to each nodule
      as follows: 0, cold; 1, decreased; 2, equal; 3, increased. The thyroid scan was
      performed 20 and 40 min after intravenous injection of 555 MBq of Tc-MIBI. The
      patients underwent fine-needle aspiration cytology (FNAC). Detailed statistical
      parameters were determined on a per-nodule basis for each qualitative and
      quantitative scan analysis, as defined by histology. RESULTS: A total of 104
      patients (93 women and 11 men; mean age 40.76+/-11.40 years, range 20-73) with a
      total number of 167 cold nodules were included in this study. When Tc-MIBI uptake
      was regarded as the criterion of malignancy in Tc-MIBI scintigraphy, the accuracy
      was between 69.46 and 92.21% on using seven different methods. In addition, FNAC
      findings indicated a sensitivity of 66.66%, a specificity of 100%, a negative
      predictive value of 95.72%, a positive predictive value of 100%, and an accuracy
      of 96.06%. Six malignant cold nodules were detected on a positive Tc-MIBI scan,
      which were determined as benign nodules on FNAC examinations. CONCLUSION: The
      study demonstrated that Tc-MIBI scanning can be complementary to other diagnostic
      techniques in patients with cold thyroid nodules. In addition, because of its
      availability, rather low cost, simple protocol, and objective semiquantitative
      information, Tc-MIBI scanning seems to hold promise in routine imaging of cold
      thyroid nodules.

PMID- 24128899
TI  - Normal biodistribution pattern and physiologic variants of 18F-DOPA PET imaging.
AB  - Dihydroxyphenylalanine (DOPA) is a neutral amino acid that resembles natural L
      dopa (dopamine precursor). It enters the catecholamine metabolic pathway of
      endogenous L-DOPA in the brain and peripheral tissues. It is amenable to labeling
      with fluorine-18(F) for PET imaging and was originally used in patients with
      Parkinson's disease to assess the integrity of the striatal dopaminergic system.
      The recent introduction and use of hybrid PET/CT scanners has contributed
      significantly to the management of a series of other pathologies including
      neuroendocrine tumors, brain tumors, and pancreatic cell hyperplasia. These
      pathologic entities present an increased activity of L-DOPA decarboxylase and
      therefore demonstrate high uptake of F-DOPA. Despite these potentially promising
      applications in several clinical fields, the role of F-DOPA has not been
      elucidated completely yet because of associated difficulties in synthesis and
      availability. Unfortunately, the available literature does not provide
      recommendations for procedures or administered activity, acquisition timing, and
      premedication with carbidopa. The aim of this paper is to outline the
      physiological biodistribution and normal variants, including possible pitfalls
      that may lead to misinterpretations of the scans in various clinical settings.

PMID- 24128900
TI  - Treatment outcomes of injection laryngoplasty using cross-linked porcine collagen
      and hyaluronic acid.
AB  - OBJECTIVE: To investigate the treatment outcomes and prognostic factors of
      injection laryngoplasty (IL) using cross-linked porcine collagen (PC) and
      hyaluronic acid (HA) in unilateral vocal fold paralysis (UVFP). STUDY DESIGN:
      Case series with chart review. SETTING: A tertiary teaching hospital. SUBJECTS
      AND METHODS: This study reviewed 60 consecutive patients with UVFP who underwent
      IL with PC (n = 33) or HA (n = 27). Objective evaluations included maximal
      phonation time (MPT) and 10-item voice handicap index (VHI-10). Kaplan-Meier
      method was applied to evaluate the subjective treatment outcomes according to the
      patients' self-assessment of symptom recurrence via chart review for the follow
      up period of 15 months. Log-rank tests were applied to evaluate the association
      between clinical factors and subjective treatment outcomes. RESULTS: Objective
      outcome measurements revealed significantly improved MPT and VHI-10 at 1, 3, and
      6 months posttreatment, with nonsignificant differences between the PC and HA
      groups. Subjective treatment outcomes also revealed a nonsignificant difference
      between the 2 groups. The median symptom-free durations were 10.9 and 14.4 months
      for the PC and HA groups, respectively. Subsequent analyses failed to identify
      prognostic significance of sex, time to treatment, etiology, side, injection
      approaches, and the presence of aspiration. No significant adverse effects
      occurred during the follow-up period. CONCLUSION: This study demonstrated
      comparable subjective and objective improvements following IL using PC or HA in
      patients with UVFP. No significant prognostic factor of IL was discovered in the
      present research. Porcine collagen and HA as medium duration materials might play
      a role in the future of IL.

PMID- 24128901
TI  - 2013 Scientific Achievement Award recipient: Eugene H. Blackstone, MD.

PMID- 24128902
TI  - Rapid 2-stage Norwood I for high-risk hypoplastic left heart syndrome and
      variants.
AB  - OBJECTIVES: Preoperative comorbidities (PCMs) are known risk factors for Norwood
      stage I (NW1). We tested the hypothesis that short-term bilateral pulmonary
      arterial banding (bPAB) before NW1 could improve the prognosis of these high-risk
      patients. METHODS: From January 2006 to October 2011, 17 high-risk patients with
      hypoplastic left heart syndrome (defined as having >=4 of the following PCMs:
      prolonged mechanical ventilation; older age; sepsis; necrotizing enterocolitis;
      hepatic, renal, or heart failure; coagulopathy; pulmonary edema; high inotropic
      requirements; anasarca; weight <2.5 kg; and cardiac arrest) were identified. In
      addition to conventional treatment of PCMs, they underwent bPAB before NW1. bPAB
      was undertaken with Silastic slings and secured with ligaclips to a luminal
      diameter of approximately 3.5 to 4.0 mm. The patency of the ductus arteriosus was
      maintained with prostaglandin. NW1 was performed using a modified, right Blalock
      Taussig shunt at a median interval of 8 days after bPAB. The data from these
      patients were retrospectively reviewed, and the 30-day mortality and 1-year
      survival were compared with the hypoplastic left heart syndrome population who
      underwent primary NW1 with <3 PCMs in the same period. RESULTS: Of the bPAB
      patients, 5 (29.4%) died before NW1. All had >=5 PCMs. Twelve patients (70.6%)
      survived to undergo NW1. One early death occurred after NW1 (8.3%). The 1-year
      survival rate for high-risk patients who underwent NW1 was 66.7%. The early
      mortality and 1-year survival for the 130 patients with <3 PCMs was 10% and 80%,
      respectively. CONCLUSIONS: Optimizing the balance between the pulmonary and
      systemic blood flow with a short period of bPAB and ductal patency can improve
      the perioperative conditions of high-risk patients before NW1. Those who survived
      bPAB and underwent NW1 had early mortality and 1-year survival comparable to the
      standard risk category, despite the severity of their initial condition. A rapid
      2-stage NW1 strategy with bPAB and prostaglandin to maintain ductal patency can
      avoid the risks of suboptimal palliation and vascular injuries associated with
      hybrid procedures.

PMID- 24128904
TI  - Postoperative noninvasive ventilation in patients undergoing coronary artery
      bypass grafting: a small step with great repercussions.

PMID- 24128905
TI  - Reply to the editor.

PMID- 24128906
TI  - Mitral valve replacement in the presence of massive calcification.

PMID- 24128907
TI  - Reply to the editor.

PMID- 24128908
TI  - Surgical management of cerebral malperfusion with acute type A aortic dissection.

PMID- 24128909
TI  - Is video-assisted thoracic lobectomy safe and successful for locally advanced non
      small cell lung cancer?

PMID- 24128910
TI  - Brainstorming on recurrence rates and underlying mechanisms of functional mitral
      regurgitation.

PMID- 24128911
TI  - Insertion of papillary muscle instead of left ventricular reduction.

PMID- 24128912
TI  - Which is more important in the potential interference on cardioprotection by
      remote ischemic preconditioning: beta-blockers or anesthetic choice?

PMID- 24128913
TI  - Definition of local and regional recurrence in the American College of Surgery
      Oncology Group Z0030 trial.

PMID- 24128914
TI  - Limitations in the use of left carotid artery turndown for interrupted aortic
      arch repair.

PMID- 24128915
TI  - Prosthetic aortic valve evaluation: Should the assessment of hemodynamic
      performance during exercise complete the analysis?

PMID- 24128916
TI  - Three-dimensional configuration of the mitral subvalvular apparatus.

PMID- 24128917
TI  - Reply to the editor.

PMID- 24128918
TI  - Sexual side effects of serotonergic antidepressants: mediated by inhibition of
      serotonin on central dopamine release?
AB  - Antidepressant-induced sexual dysfunction adversely affects the quality of life
      of antidepressant users and reduces compliance with treatment. Animal models
      provide an instructive approach for examining potential sexual side effects of
      novel drugs. This review discusses the stability and reproducibility of our
      standardized test procedure that assesses the acute, subchronic and chronic
      effects of psychoactive compounds in a 30 minute mating test. In addition, we
      present an overview of the effects of several different (putative)
      antidepressants on male rat sexual behavior, as tested in our standardized test
      procedure. By comparing the effects of these mechanistically distinct
      antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and
      S32006), this review discusses the putative mechanism underlying sexual side
      effects of antidepressants and their normalization. This review shows that sexual
      behavior is mainly inhibited by antidepressants that increase serotonin
      neurotransmission via blockade of serotonin transporters, while those that mainly
      increase the levels of dopamine and noradrenaline are devoid of sexual side
      effects. Those sexual disturbances cannot be normalized by simultaneously
      increasing noradrenaline neurotransmission, but are normalized by increasing both
      noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that
      the sexual side effects of selective serotonin reuptake inhibitors may be
      mediated by their inhibitory effects on dopamine signaling in sex brain circuits.
      Clinical development of novel antidepressants should therefore focus on compounds
      that simultaneously increase both serotonin and dopamine signaling.

PMID- 24128919
TI  - Effect of substituent of terpyridines on the in vitro antioxidant,
      antitubercular, biocidal and fluorescence studies of copper(II) complexes with
      clioquinol.
AB  - An octahedral complexes of copper with clioquinol(CQ) and substituted terpyridine
      have been synthesized. The Cu(II) complexes have been characterized by elemental
      analyses, thermogravimetric analyses, magnetic moment measurements, FT-IR,
      electronic, (1)HNMR and FAB mass spectra. Antimycobacterial screening of ligand
      and its copper compound against Mycobacterium tuberculosis shows clear
      enhancement in the antitubercular activity upon copper complexation. Ferric
      reducing anti-oxidant power of all complexes were measured. The fluorescence
      spectra of complexes show red shift, which may be due to the chelation by the
      ligands to the metal ion. It enhances ligand ability to accept electrons and
      decreases the electron transition energy. The antimicrobial efficiency of the
      complexes were tested on five different microorganisms and showed good biological
      activity. 

PMID- 24128920
TI  - Anharmonic IR and Raman spectra and electronic and vibrational
      (hyper)polarizabilities of barbituric, 2-thiobarbituric and 2-selenobarbituric
      acids.
AB  - Infrared, Raman and electronic absorption spectra, electronic and vibrational
      (hyper)polarizabilities, of barbituric, 2-thiobarbituric and 2-selenobarbituric
      acids were studied in gas using ab initio and density functional theory levels.
      The vibrational spectra were computed using harmonic and anharmonic methods.
      Anharmonic contributions improve the agreement between calculated and available
      experimental wavenumbers, especially in the highest-energy spectral region
      (wavenumbers >1700 cm(-1)). Vibrational and electronic transitions potentially
      useful to identify the investigated compounds were explored. The electronic and
      vibrational hyperpolarizabilities for the IDRI nonlinear optical (NLO) process at
      the lambda value of 790 nm were computed. Supported by spectroscopic results,
      electronic and vibrational polarizabilities and second-order
      hyperpolarizabilities increase progressively in the order barbituric acid<2
      thiobarbituric acid<2-selenobarbituric acid. The seleno-derivative is predicted
      to be ca. three/four times more hyperpolarizable than the barbituric acid. The Se
      >O or Se->S substitutions can be practical strategies to enhances the NLO
      properties of barbituric and thiobarbituric acid-based materials.

PMID- 24128921
TI  - Experimental and theoretical study of absorption spectrum of the (CH3)2CO...HF
      complex. Influence of anharmonic interactions on the frequency and intensity of
      the C=O and H-F stretching bands.
AB  - IR absorption spectra of mixtures (CH3)2CO/HF and free (CH3)2CO molecules are
      recorded in the region of 4000-900 cm(-1) with a Bruker IFS-125 HR vacuum Fourier
      spectrometer at room temperature with a resolution up to 0.02 cm(-1). Spectral
      characteristics of the 2nu(C=O) overtone band of free acetone are reliably
      measured. The nu1(HF) and nu(C=O) absorption bands of the (CH3)2CO...HF complex
      are obtained by subtracting the absorption bands of free HF and acetone and
      absorption lines of atmospheric water from the experimental spectrum of mixtures.
      The experimental data are compared with theoretical results obtained from
      variational solutions of 1D-4D vibrational Schrodinger equations. The anharmonic
      potential energy and dipole moment surfaces used in the calculations were
      computed in the MP2/6-311++G(2d,2p) approximation with corrections for the basis
      set superposition error. Comparison of the data derived from solutions for
      different combinations of vibrational degrees of freedom shows that taking the
      inter-mode anharmonic interactions into account has different effects on the
      transition frequencies and intensities. Particular attention has been given to
      elucidation of the influence of anharmonic coupling of the H-F and C=O stretches
      with the low-frequency intermolecular modes on their frequencies and intensities
      and the strength of resonance between the fundamental H-F and the first overtone
      C=O transitions.

PMID- 24128922
TI  - Photophysical investigations on supramolecular fullerene/phthalocyanine charge
      transfer interactions in solution.
AB  - The photophysical features of non-covalently linked fullerenes C60 and C70 with a
      designed free-base phthalocyanine, namely, 2,3,9,10,16,17,23,24-octakis
      (octyloxy)-29H,31H-phthalocyanine (1) have been investigated employing various
      spectroscopic tools like UV-vis absorption spectrophotometry, steady state and
      time resolved fluorescence along with proton NMR measurements in toluene. The
      ground state interaction between fullerenes and 1 is nicely demonstrated with the
      appearance of well defined charge transfer absorption bands in the visible region
      of the electronic spectra. Steady state fluorescence experiment reveals efficient
      quenching of the excited singlet state of 1 in presence of both C60 and C70. The
      average values of binding constants for the non-covalent complexes of C60 and C70
      with 1 are determined to be ~18,150 and ~32,000 dm(3) mol(-1), respectively. The
      magnitude of K suggests that 1 preferentially binds C70 in comparison to C60
      although average value of selectivity in binding is measured to be low (~1.75).
      Time resolved emission measurements establish photoinduced energy transfer from
      the excited singlet state of 1 to fullerene in toluene. Measurements of free
      energy of electron transfer and free energy of radical ion-pair formation elicit
      that C70/1 complex is stabilized more in comparison to C60/1 complex regarding
      generation of charge-separated state. Proton NMR studies provide very good
      support in favor of effective ground state complexation between fullerenes and 1.
      Semi empirical theoretical calculations on fullerene/1 systems in vacuo
      substantiate the stronger binding between C70 and 1 in comparison to C60/1 system
      in terms of heat of formation value of the respective complexes, and determine
      the orientation of bound guest (here C70) towards the plane of 1 during
      complexation.

PMID- 24128923
TI  - Perinatal quality indicators: yardsticks for quality of care, measures of
      population health.

PMID- 24128924
TI  - The effect of prolapse repair on urinary flow rates and the relationship to
      changes in the ultrasound appearance of the bladder neck.
AB  - OBJECTIVE: To assess whether specific changes in bladder neck morphology, caused
      by an anterior repair operation, are associated with resolution of overactive
      bladder and improved urinary flow rates. STUDY DESIGN: Sixty-four women with
      urgency documented on the urgency perception scale (UPS) underwent an anterior
      repair. Their preoperative flow studies were compared to those 8 weeks
      postoperatively. Flow rates were compared in those women who reported improved or
      cured urgency to those who reported no effect. Resolution of urgency was
      correlated with the change in bladder neck angulation (posterior urethrovesical
      angle-PUA). RESULTS: 55% (35/64) women reported no urgency after the anterior
      repair. A further 19% (12/64) were improved and 26% (17/64) were no better.
      Patients who were cured or improved showed a significant increase in their flow
      rates after surgery (mean flow=15 before and 17.6 ml/s after) (Mann-Whitney
      p=0.04). There was a significant change (increase in the PUA angle/straightening
      of the angle between the bladder and urethra) from a mean value of 123 degrees
      (SD 49.3) preoperatively to a mean value of 146.8 (SD 29.2) post operatively
      (p<0.001). Despite an increase in PUA, this was not correlated with an increase
      in the maximum flow rate centile (p=0.45, r=0.10). CONCLUSIONS: An anterior
      repair results in increased maximum urinary flow rates but this does not
      correlate to changes in the appearance of the bladder neck.

PMID- 24128925
TI  - Modified prepubic TVT-obturator tape procedure versus the conventional method: a
      preliminary study.
AB  - OBJECTIVE: To compare the efficacy and safety of the modified prepubic tension
      free vaginal tape-obturator (PTVT-O) system procedure with the original TVT-O
      methods. STUDY DESIGN: One hundred and ninety women with urodynamic stress
      incontinence (USI) were included in this study (93 cases in the TVT-O group and
      97 in the PTVT-O group). Clinical assessments before and one year after surgery
      included urinalyses, 1-h pad tests, urodynamic studies, and a personal interview
      with the overactive bladder symptom score (OABSS) questionnaire. RESULTS: There
      were no differences between the two groups in mean age, parity, menopausal
      status, mean operative time and subjective cure rates (P>0.05), but the efficacy
      of surgery (cure and improvement) in the PTVT-O group was significantly higher
      than that in the TVT-O group (P=0.038). Complication rates and visual analog
      scale (VAS) scores were found to be similar (P>0.05). OABSS decreased
      significantly after surgery in both groups (P<0.05) although all urodynamic
      parameters revealed no significant difference after both procedures (P>0.05).
      CONCLUSION: Our modified procedure is a safe and effective treatment for female
      USI. It has an advantage over the original TVT-O with better surgical efficacy
      and comparable postoperative pain, although the follow-up times in this study are
      different.

PMID- 24128926
TI  - Maternal death from stroke: a thirty year national retrospective review.
AB  - OBJECTIVE: In the United Kingdom (UK), the maternal mortality rate from stroke is
      reported at 0.3/100,000 deliveries, but only antenatal data have previously been
      reviewed. We hypothesise that the true rate is much higher due to a propensity
      for stroke occurring in the post-partum period, and that the rate will rise in
      parallel with trends of increasing maternal age and medical co-morbidities. Our
      objectives are to investigate the UK stroke mortality rate in pregnancy and the
      puerperium, and to examine temporal changes in fatal maternal strokes over a 30
      year period. STUDY DESIGN: Retrospective review of stroke-related maternal deaths
      reported to the UK confidential enquiries into maternal death between 1979 and
      2008, encompassing 21,514,457 maternities. In accordance with the ICD.10
      classification, cases were divided into direct or indirect deaths. Late and
      coincidental deaths were not included in analyses. Lessons from sub-standard care
      associated with maternal death from stroke were collated. RESULTS: In 1979-2008
      there were 347 maternal deaths from stroke: 139 cases were direct deaths, i.e.
      the fatal stroke was a direct result of pregnancy. The incidence of fatal stroke
      is relatively constant at 1.61/100,000 maternities, with a 13.9% (95% CI 12.6
      15.3) proportional mortality rate. Intracranial haemorrhage was the single
      greatest cause of maternal death from stroke. CONCLUSION: This is the largest UK
      study examining the incidence of fatal maternal stroke in pregnancy and the
      puerperium. Our results highlight the high proportion of women who die from
      stroke in the puerperium. Sub-standard care featured especially in regard to
      management of dangerously high systolic blood pressure levels. These deaths
      highlight the importance of education in managing rapid-onset hypertension and
      superimposed coagulopathies.

PMID- 24128927
TI  - Health status of alfalfa leafcutting bee larvae (Hymenoptera: Megachilidae) in
      United States alfalfa seed fields.
AB  - We conducted a broad geographic survey in the northwestern United States to
      quantify production losses in the alfalfa leafcutting bee (Megachile rotundata
      (F.), Hymenoptera: Megachilidae), a solitary pollinator used extensively in
      alfalfa seed production. Viable larvae were found in only 47.1% of the nest cells
      collected at the end of the season. Most of the rest of the cells contained
      pollen balls (typified by a provision but no larva; 16.7%), unknown causes of
      mortality (15.5%), or larvae killed by chalkbrood (8.0%). Prevalence of pollen
      balls was correlated positively with bee release rates and negatively with
      alfalfa stand age. The unknown mortality was correlated with the U.S. Department
      of Agriculture-Plant Hardiness Zone, and thus, some of the mortality may be
      caused by high temperature extremes, although the nesting season degree-days were
      not correlated with this mortality. Chalkbrood prevalence was correlated with
      possible nesting-resource or crowding-related factors, such as the number of bees
      released per hectare and the number of shelters used, but not with nesting board
      disinfection practices. Vapona is used to control parasitoids when the parent
      bees are incubated before release, and use of this fumigant was associated with
      an increase in both chalkbrood and diapausing offspring, although any reason for
      these correlations are unknown. This survey quantifies the variation in the
      quality of alfalfa leafcutting bee cocoons produced across much of the U.S.
      alfalfa seed production area. 

PMID- 24128928
TI  - Phylogeny of the Atlantic and Pacific species of Ligophorus (Monogenea:
      Dactylogyridae): morphology vs. molecules.
AB  - Within ectoparasitic fish monogeneans, the genus Ligophorus contains a high
      number of species from which several were recently described. The precise
      determination of their taxonomic status requires robust diagnostic morphologic
      features that rely predominantly on a restricted set of sclerotized structures.
      In the present study, these morphological characters were used for the
      reconstruction of a phylogenetic tree, which was compared with a tree built from
      molecular data (28S and ITS1 DNA sequences). Thirty-eight morphological
      characters were used in 29 species of Ligophorus from the Atlantic and Pacific
      regions and 5 species within close genera of Dactylogyridae. The morphological
      and molecular phylogenetic trees are congruent and suggest that the genus
      Ligophorus is monophyletic, and that species parasitizing Liza spp. and Chelon
      labrosus occupy basal positions. The present study suggests that host switching
      is a common event in this host-parasite association, because about half of the
      species infecting the same host species are not close relatives. Following host
      switching, dispersal with vicariance is probably an important force shaping the
      present distribution and diversity of Ligophorus. The pattern of occurrence of
      Ligophorus spp. on Mugil cephalus supports that reproductive isolation and
      therefore parallel speciation are taking place among these parasitic organisms. 

PMID- 24128929
TI  - Can we optimise the exercise training prescription to maximise improvements in
      mitochondria function and content?
AB  - BACKGROUND: While there is agreement that exercise is a powerful stimulus to
      increase both mitochondrial function and content, we do not know the optimal
      training stimulus to maximise improvements in mitochondrial biogenesis. SCOPE OF
      REVIEW: This review will focus predominantly on the effects of exercise on
      mitochondrial function and content, as there is a greater volume of published
      research on these adaptations and stronger conclusions can be made. MAJOR
      CONCLUSIONS: The results of cross-sectional studies, as well as training studies
      involving rats and humans, suggest that training intensity may be an important
      determinant of improvements in mitochondrial function (as determined by
      mitochondrial respiration), but not mitochondrial content (as assessed by citrate
      synthase activity). In contrast, it appears that training volume, rather than
      training intensity, may be an important determinant of exercise-induced
      improvements in mitochondrial content. Exercise-induced mitochondrial adaptations
      are quickly reversed following a reduction or cessation of physical activity,
      highlighting that skeletal muscle is a remarkably plastic tissue. Due to the
      small number of studies, more research is required to verify the trends
      highlighted in this review, and further studies are required to investigate the
      effects of different types of training on the mitochondrial sub-populations and
      also mitochondrial adaptations in different fibre types. Further research is also
      required to better understand how genetic variants influence the large individual
      variability for exercise-induced changes in mitochondrial biogenesis. GENERAL
      SIGNIFICANCE: The importance of mitochondria for both athletic performance and
      health underlines the importance of better understanding the factors that
      regulate exercise-induced changes in mitochondrial biogenesis. This article is
      part of a Special Issue entitled Frontiers of Mitochondrial Research.

PMID- 24128930
TI  - Trichoderma reesei CE16 acetyl esterase and its role in enzymatic degradation of
      acetylated hemicellulose.
AB  - BACKGROUND: Trichoderma reesei CE16 acetyl esterase (AcE) is a component of the
      plant cell wall degrading system of the fungus. The enzyme behaves as an exo
      acting deacetylase removing acetyl groups from non-reducing end sugar residues.
      METHODS: In this work we demonstrate this exo-deacetylating activity on natural
      acetylated xylooligosaccharides using MALDI ToF MS. RESULTS: The combined action
      of GH10 xylanase and acetylxylan esterases (AcXEs) leads to formation of neutral
      and acidic xylooligosaccharides with a few resistant acetyl groups mainly at
      their non-reducing ends. We show here that these acetyl groups serve as targets
      for TrCE16 AcE. The most prominent target is the 3-O-acetyl group at the non
      reducing terminal Xylp residues of linear neutral xylooligosaccharides or on
      aldouronic acids carrying MeGlcA at the non-reducing terminus. Deacetylation of
      the non-reducing end sugar may involve migration of acetyl groups to position 4,
      which also serves as substrate of the TrCE16 esterase. CONCLUSION: Concerted
      action of CtGH10 xylanase, an AcXE and TrCE16 AcE resulted in close to complete
      deacetylation of neutral xylooligosaccharides, whereas substitution with MeGlcA
      prevents removal of acetyl groups from only a small fraction of the aldouronic
      acids. Experiments with diacetyl derivatives of methyl beta-d-xylopyranoside
      confirmed that the best substrate of TrCE16 AcE is 3-O-acetylated Xylp residue
      followed by 4-O-acetylated Xylp residue with a free vicinal hydroxyl group.
      GENERAL SIGNIFICANCE: This study shows that CE16 acetyl esterases are crucial
      enzymes to achieve complete deacetylation and, consequently, complete the
      saccharification of acetylated xylans by xylanases, which is an important task of
      current biotechnology.

PMID- 24128931
TI  - The Salmonella enterica ZinT structure, zinc affinity and interaction with the
      high-affinity uptake protein ZnuA provide insight into the management of
      periplasmic zinc.
AB  - BACKGROUND: In Gram-negative bacteria the ZnuABC transporter ensures adequate
      zinc import in Zn(II)-poor environments, like those encountered by pathogens
      within the infected host. Recently, the metal-binding protein ZinT was suggested
      to operate as an accessory component of ZnuABC in periplasmic zinc recruitment.
      Since ZinT is known to form a ZinT-ZnuA complex in the presence of Zn(II) it was
      proposed to transfer Zn(II) to ZnuA. The present work was undertaken to test this
      claim. METHODS: ZinT and its structural relationship with ZnuA have been
      characterized by multiple biophysical techniques (X-ray crystallography, SAXS,
      analytical ultracentrifugation, fluorescence spectroscopy). RESULTS: The metal
      free and metal-bound crystal structures of Salmonella enterica ZinT show one
      Zn(II) binding site and limited structural changes upon metal removal.
      Spectroscopic titrations with Zn(II) yield a KD value of 22+/-2nM for ZinT, while
      those with ZnuA point to one high affinity (KD<20nM) and one low affinity Zn(II)
      binding site (KD in the micromolar range). Sedimentation velocity experiments
      established that Zn(II)-bound ZinT interacts with ZnuA, whereas apo-ZinT does
      not. The model of the ZinT-ZnuA complex derived from small angle X-ray scattering
      experiments points to a disposition that favors metal transfer as the metal
      binding cavities of the two proteins face each other. CONCLUSIONS: ZinT acts as a
      Zn(II)-buffering protein that delivers Zn(II) to ZnuA. GENERAL SIGNIFICANCE:
      Knowledge of the ZinT-ZnuA relationship is crucial for understanding bacterial
      Zn(II) uptake.

PMID- 24128932
TI  - MitoTimer: a novel tool for monitoring mitochondrial turnover.
AB  - Fluorescent Timer, or DsRed1-E5, is a mutant of the red fluorescent protein,
      dsRed, in which fluorescence shifts over time from green to red as the protein
      matures. This molecular clock gives temporal and spatial information on protein
      turnover. To visualize mitochondrial turnover, we targeted Timer to the
      mitochondrial matrix with a mitochondrial-targeting sequence (coined "MitoTimer")
      and cloned it into a tetracycline-inducible promoter construct to regulate its
      expression. Here we report characterization of this novel fluorescent reporter
      for mitochondrial dynamics. Tet-On HEK 293 cells were transfected with pTRE-tight
      MitoTimer and production was induced with doxycycline (Dox). Mitochondrial
      distribution was demonstrated by fluorescence microscopy and verified by
      subcellular fractionation and western blot analysis. Dox addition for as little
      as 1 h was sufficient to induce MitoTimer expression within 4 h, with persistence
      in the mitochondrial fraction for up to 6 d. The color-specific conformation of
      MitoTimer was stable after fixation with 4% paraformaldehyde. Ratiometric
      analysis of MitoTimer revealed a time-dependent transition from green to red over
      48 h and was amenable to analysis by fluorescence microscopy and flow cytometry
      of whole cells or isolated mitochondria. A second Dox administration 48 h after
      the initial induction resulted in a second round of expression of green
      MitoTimer. The extent of new protein incorporation during a second pulse was
      increased by administration of a mitochondrial uncoupler or simvastatin, both of
      which trigger mitophagy and biogenesis. MitoTimer is a novel fluorescent reporter
      protein that can reveal new insights into mitochondrial dynamics within cells.
      Coupled with organelle flow cytometry, it offers new opportunities to investigate
      mitochondrial subpopulations by biochemical or proteomic methods. 

PMID- 24128933
TI  - The cooccurrence of interictal discharges and seizures in pediatric sleep
      disordered breathing.
AB  - Studies in the literature data have shown that the prevalence of obstructive
      sleep apnea (OSA) in children with epilepsy is high and that treatment for OSA
      leads to a reduction in the number of seizures; by contrast, few studies have
      demonstrated an increased prevalence of interictal epileptiform discharges (IEDs)
      or epilepsy in children with sleep-disordered breathing (SDB). The aim of the
      present study was to confirm the high prevalence of IEDs or epilepsy in a large
      sample of children with SDB and to collect follow-up data. Children were
      recruited prospectively and underwent their first video-polysomnography (video
      PSG) for SDB in a teaching hospital sleep center. Of the 298 children who
      fulfilled the diagnostic criteria for sleep-disordered breathing, 48 (16.1%)
      children were found to have IEDs, three of these 48 children were also found to
      have nocturnal seizures (two females diagnosed with rolandic epilepsy and a male
      diagnosed with frontal lobe epilepsy). Only 11 subjects underwent a second video
      PSG after 6months; at the second video-PSG, the IEDs had disappeared in six
      subjects, who also displayed a reduced AHI and an increased mean overnight
      saturation. Thirty-eight of the 250 children without IEDs underwent a second
      video-PSG after 6months. Of these 250 children, four, who did not display any
      improvement in the respiratory parameters and were found to experience numerous
      stereotyped movements during sleep, were diagnosed with nocturnal frontal lobe
      epilepsy. Our study confirms the high prevalence of IEDs in children with SDB.
      Follow-up data indicate that they may recede over time, accompanied by an
      improvement of sleep respiratory parameters. 

PMID- 24128934
TI  - Screening for suicidal ideation in children with epilepsy.
AB  - Given the FDA's warning regarding the potential connection between suicidal
      behavior and antiepileptic drugs, this study examined methods by which to detect
      suicidal ideation in children with epilepsy. It compared the sensitivity,
      specificity, and area under the curve for identifying children with suicidal
      behavior using the Child Behavior Checklist (CBCL) and a structured psychiatric
      interview. Parent-completed CBCLs provided behavioral problem scores on 177
      children with epilepsy, aged 5-16years. Psychiatric diagnoses were made based on
      separate child and parent structured psychiatric interviews about the child. The
      children answered questions on suicidal behaviors during the interview. A
      clinically elevated score in the CBCL Total Problems scale and having more than
      one psychiatric diagnosis, irrespective of the type of diagnosis, were
      significant predictors and correctly classified children with suicidal ideation
      in 79% of the cases based on the CBCL and 80% of the cases with more than one
      psychiatric diagnosis. These findings indicate that elevated CBCL Total Problems
      scores, a commonly used instrument, can screen and identify risk for suicidal
      behavior in children with epilepsy. Additionally, irrespective of diagnosis, if a
      child with epilepsy has more than one psychiatric diagnosis, further assessment
      of suicidal behavior is warranted. Importantly, the results underscore the
      utility of having parents complete a questionnaire in the waiting room in order
      to identify children with epilepsy at risk for suicidal behavior. 

PMID- 24128935
TI  - Impact of TCF7L2 single nucleotide polymorphisms on hydrochlorothiazide-induced
      diabetes.
AB  - OBJECTIVE: Thiazide diuretics have been associated with increased risk for new
      onset diabetes (NOD), but pharmacogenetic markers of thiazide-induced NOD are not
      well studied. Single nucleotide polymorphisms (SNPs) in the transcription factor
      7-like 2 gene (TCF7L2) represent the strongest and most reproducible genetic
      associations with diabetes. We investigated the association of tag SNPs in TCF7L2
      with thiazide-induced NOD. METHODS: We identified cases that developed NOD and
      age, sex, and race/ethnicity-matched controls from the INternational VErapamil SR
      Trandolapril STudy (INVEST). INVEST compared cardiovascular outcomes between two
      antihypertensive treatment strategies in ethnically diverse patients with
      hypertension and coronary artery disease. We genotyped 101 TCF7L2 tag SNPs and
      used logistic regression to test for pharmacogenetic (SNP*hydrochlorothiazide
      treatment) interactions. Permuted interaction P values were corrected with the
      PACT test and adjusted for diabetes-related variables. RESULTS: In INVEST whites,
      we observed three TCF7L2 SNPs with significant SNP*treatment interactions for
      NOD. The strongest pharmacogenetic interaction was observed for rs7917983
      [synergy index 3.37 (95% CI 1.72-6.59), P=5.0*10, PACT=0.03], which was
      associated with increased NOD risk in hydrochlorothiazide-treated patients [odds
      ratio 1.53 (1.04-2.25), P=0.03] and decreased NOD risk in non hydrochlorothiazide
      treated patients [odds ratio 0.48 (0.27-0.86), P=0.02]. The TCF7L2 SNP rs4506565,
      previously associated with diabetes, showed a similar, significant
      pharmacogenetic association. CONCLUSION: Our results suggest that
      hydrochlorothiazide treatment is an environmental risk factor that increases
      diabetes risk beyond that attributed to TCF7L2 variation in white, hypertensive
      patients. Further study and replication of our results is needed to confirm
      pharmacogenetic influences of TCF7L2 SNPs on thiazide-induced NOD.

PMID- 24128936
TI  - PharmGKB summary: venlafaxine pathway.

PMID- 24128938
TI  - Yersinia enterocolitica infections associated with improperly pasteurized milk
      products: southwest Pennsylvania, March-August, 2011.
AB  - In July 2011, a cluster of Yersinia enterocolitica infections was detected in
      southwestern Pennsylvania, USA. We investigated the outbreak's source and scope
      in order to prevent further transmission. Twenty-two persons were diagnosed with
      yersiniosis; 16 of whom reported consuming pasteurized dairy products from dairy
      A. Pasteurized milk and food samples were collected from this dairy. Y.
      enterocolitica was isolated from two products. Isolates from both food samples
      and available clinical isolates from nine dairy A consumers were
      indistinguishable by pulsed-field gel electrophoresis. Environmental and
      microbiological investigations were performed at dairy A and pasteurization
      deficiencies were noted. Because consumption of pasteurized milk is common and
      outbreaks have the potential to become large, public health interventions such as
      consumer advisories or closure of the dairy must be implemented quickly to
      prevent additional cases if epidemiological or laboratory evidence implicates
      pasteurized milk as the outbreak source.

PMID- 24128937
TI  - Expression of UGT2B7 is driven by two mutually exclusive promoters and
      alternative splicing in human tissues: changes from prenatal life to adulthood
      and in kidney cancer.
AB  - OBJECTIVE: UDP-glucuronosyltransferase 2B7 (UGT2B7) plays a major detoxification
      role in commonly prescribed drugs and endogenous lipophilic molecules. Additional
      exons and multiple alternative splicing events (ASEs) at the UGT2B7 locus were
      recently discovered. MATERIALS AND METHODS: Novel and classical ASEs were
      quantified in 27 human tissues, as well as in fetal and tumoral tissues. The
      activity of the alternative UGT2B7 promoters was studied in cell lines. RESULTS:
      UGT2B7 expression is driven by an alternate promoter 1a associated with
      transcripts containing exon 1b, which is located ~44 kb upstream of the known
      promoter 1 associated with transcripts containing exon 1 required for enzyme
      activity. The exon 1 was expressed most abundantly in the liver and
      gastrointestinal tract, whereas exon 1b was expressed predominantly in other
      extrahepatic tissues. Experimental evidence indicated endogenous translation that
      yields alternative UGT2B7s derived from the use of exon 1b are enzymatically
      inactive. Alternate 5' ASE predominates in fetal tissues (kidney, lung) and
      kidney tumor samples compared with normal adult kidney. These changes further
      correlate with reduced glucuronidation in neoplastic kidneys. This differential
      expression pattern was further confirmed using four liver and kidney cell lines
      and was consistent with the differential usage of alternate promoters in hepatic
      (promoter 1) and kidney cells (1a). CONCLUSION: UGT2B7 is characterized by two
      mutually exclusive exons 1, both flanked by a unique 5' promoter region. Data
      also indicated a switch toward functional enzyme upon maturation in the kidney
      and reversal of this process in neoplastic cells, considerably modifying the
      glucuronidation potential across human tissues and cells.

PMID- 24128939
TI  - Anatomical restrictions in the surgical excision of scalp squamous cell
      carcinomas: does this affect local recurrence and regional nodal metastases?
AB  - Squamous cell carcinomas (SCCs) of the skin of the scalp have the potential for
      regional metastases. Microscopically, clearance may be less than the optimal
      dimensions. We report 101 SCCs of the scalp treated surgically under the care of
      a single oral and maxillofacial surgeon. Forty-two of the study patients had deep
      margins that were clear by less than 2mm, of whom five had margins that involved
      pericranium+/-skull. Our study demonstrated a local recurrence rate of 6% and a
      regional recurrence rate of 7%. All patients presented with relapse of the
      disease within 18 months of primary surgery. The evidence presented in this study
      suggests that in SCCs of the scalp, less than ideal surgical margin clearance,
      entirely due to anatomical restrictions, does not appear to substantially affect
      regional recurrence, but increases the risk of local recurrence. 

PMID- 24128941
TI  - Predictive accuracy of nephrometric scores can be improved by adding clinical
      patient characteristics: a novel algorithm combining anatomic tumour complexity,
      body mass index, and Charlson comorbidity index to depict perioperative
      complications after nephron-sparing surgery.

PMID- 24128940
TI  - Evaluating the fitness cost of protein expression in Saccharomyces cerevisiae.
AB  - Protein metabolism is one of the most costly processes in the cell and is
      therefore expected to be under the effective control of natural selection. We
      stimulated yeast strains to overexpress each single gene product to approximately
      1% of the total protein content. Consistent with previous reports, we found that
      excessive expression of proteins containing disordered or membrane-protruding
      regions resulted in an especially high fitness cost. We estimated these costs to
      be nearly twice as high as for other proteins. There was a ten-fold difference in
      cost if, instead of entire proteins, only the disordered or membrane-embedded
      regions were compared with other segments. Although the cost of processing bulk
      protein was measurable, it could not be explained by several tested protein
      features, including those linked to translational efficiency or intensity of
      physical interactions after maturation. It most likely included a number of
      individually indiscernible effects arising during protein synthesis, maturation,
      maintenance, (mal)functioning, and disposal. When scaled to the levels normally
      achieved by proteins in the cell, the fitness cost of dealing with one amino acid
      in a standard protein appears to be generally very low. Many single amino acid
      additions or deletions are likely to be neutral even if the effective population
      size is as large as that of the budding yeast. This should also apply to
      substitutions. Selection is much more likely to operate if point mutations affect
      protein structure by, for example, extending or creating stretches that tend to
      unfold or interact improperly with membranes. 

PMID- 24128942
TI  - Numerical investigation of ultrasound reflection and backscatter measurements in
      cancellous bone on various receiving areas.
AB  - In this study, new ultrasound reflection and backscatter measurements in
      cancellous bone using a membrane-type hydrophone are proposed. A membrane
      hydrophone made of a piezoelectric polymer film mounted on an annular frame
      allows an incident ultrasound wave to pass through its aperture because it has no
      backing material. Therefore, in measurements using the membrane hydrophone, the
      receiving area could be located independently from the transmitting area. In
      addition, the size and shape of the receiving area, which corresponded to those
      of the electrode deposited on the piezoelectric film, could be arranged in
      various ways. To investigate the validity of the proposed measurements, before
      bench-top experiments, the reflected and backscattered waves from cancellous bone
      were numerically simulated using a finite-difference time-domain method. The
      reflection and backscatter parameters were measured on various receiving areas,
      and their correlation coefficients with the structural parameters in the
      cancellous bone were derived. The simulated results suggested that appropriate
      receiving areas for the reflection and backscatter measurements could exist and
      that the proposed measurements could be more effective for evaluating bone
      properties than conventional measurements. 

PMID- 24128943
TI  - Cross-section analyses of attitudes towards science and nature from the
      International Social Survey Programme 1993, 2000, and 2010 surveys.
AB  - This paper explores public attitudes towards science and nature in twelve
      countries using data from the International Social Survey Programme environment
      modules of 1993, 2000, and 2010. Analysis of attitude items indicates
      technocentric and pessimistic dimensions broadly related to the Dominant Social
      Paradigm and New Environmental Paradigm. A bi-axial dimension scale is utilized
      to classify respondents among four environmental knowledge orientations.
      Discernible and significant patterns are found among countries and their
      populations. Relationships with other substantial variables in the surveys are
      discussed and findings show that the majority of industrialized countries are
      clustered in the rational ecologist categorization with respondents possessing
      stronger ecological consciousness and optimism towards the role of modern
      institutions, science, and technology in solving environmental problems. 

PMID- 24128944
TI  - Steroid-responsive meningitis-arteritis in Nova Scotia duck tolling retrievers.

PMID- 24128945
TI  - Identification of inadequate maternal progesterone concentrations in nulliparous
      dairy heifers and treatment with human chorionic gonadotrophin.
AB  - Plasma progesterone concentrations were estimated for 381 nulliparous dairy
      heifers from eight farms on days 4-6 after insemination. Heifers were
      synchronised using two treatments of prostaglandin F2alpha (PGF2alpha) 11 days
      apart. Alternate heifers were treated with 1500 IU human chorionic gonadotrophin
      (hCG) at the time of sampling, and the pregnancy status assessed ~35 days after
      insemination. Heifers with no corpus luteum (CL; n-30) at the second PGF2alpha
      had lower progesterone concentrations (P<0.001) and pregnancy rates (PR; P=0.001)
      compared with heifers with CL (n=351, defined as cyclic). The risk of no CL
      increased in heifers <15 months of age (OR=7.5, P<0.001) and with body condition
      score <2.5 (OR=4.5, P=0.001). Those with no CL were removed from further
      analysis. The 20 per cent cyclic control heifers with progesterone concentrations
      <=2 ng/ml on days 4-6 had lower PRs compared with those with higher
      concentrations (42 per cent vs 64 per cent, OR=0.3, P=0.01). There was no overall
      effect of hCG on PR compared with controls (51 per cent vs 60 per cent, P=0.10).
      However, heifers with high progesterone on days 4-6 (>2 ng/ml) had a lower PR
      after treatment (51 per cent vs 64 per cent, OR=0.6, P=0.02). Heifers inseminated
      with sexed (n=18) compared with conventional (n=333) semen had a decreased PR (33
      per cent vs 57 per cent, OR=0.2, P=0.01). This study demonstrates that higher
      plasma progesterone concentrations as early as days 4-6 after insemination have a
      positive effect on first insemination PR, but there was no beneficial effect of
      hCG treatment on these days in dairy heifers.

PMID- 24128946
TI  - [Experts boards and consensus].

PMID- 24128947
TI  - Uncoupling neurovascular coupling: putative pathways of cerebrovascular
      regulation?

PMID- 24128948
TI  - Reply to Willie.

PMID- 24128950
TI  - Counseling and provision of long-acting reversible contraception in the US:
      national survey of nurse practitioners.
AB  - OBJECTIVE: Nurse practitioners (NPs) provide frontline care in women's health,
      including contraception, an essential preventive service. Their importance for
      contraceptive care will grow, with healthcare reforms focused on affordable
      primary care. This study assessed practice and training needs to prepare NPs to
      offer high-efficacy contraceptives - intrauterine devices (IUDs) and implants.
      METHOD: A US nationally representative sample of nurse practitioners in primary
      care and women's health was surveyed in 2009 (response rate 69%, n=586) to assess
      clinician knowledge and practices, guided by the CDC US Medical Eligibility
      Criteria for Contraceptive Use. RESULTS: Two-thirds of women's health NPs (66%)
      were trained in IUD insertions, compared to 12% of primary care NPs.
      Contraceptive counseling that routinely included IUDs was low overall (43%).
      Nurse practitioners used overly restrictive patient eligibility criteria,
      inconsistent with CDC guidelines. Insertion training (aOR=2.4, 95%CI: 1.10 5.33)
      and knowledge of patient eligibility (aOR=2.9, 95%CI: 1.91 4.32) were associated
      with IUD provision. Contraceptive implant provision was low: 42% of NPs in
      women's health and 10% in primary care. Half of NPs desired training in these
      methods. CONCLUSION: Nurse practitioners have an increasingly important position
      in addressing high unintended pregnancy in the US, but require specific training
      in long-acting reversible contraceptives.

PMID- 24128952
TI  - Accreditation options broaden for acute care hospitals.

PMID- 24128951
TI  - American adults eligible for the Supplemental Nutritional Assistance Program
      consume more sugary beverages than ineligible adults.
AB  - BACKGROUND: There is considerable debate about whether sugar-sweetened beverages
      (SSBs) should be allowable purchases with benefits from the Supplemental
      Nutrition Assistance Program (SNAP). PURPOSE: To examine national patterns in
      adult consumption of SSBs by SNAP eligibility. METHODS: Cross-sectional analysis
      of 24-hour dietary recall data obtained from the National Health and Nutrition
      Examination Survey 2003-2010 (N=17,198), analyzed in 2013. RESULTS: In 2003-2010,
      65% of adults receiving SNAP consumed SSBs, averaging 307 cal daily, and 74 g of
      sugar. Compared to adults ineligible for SNAP, adults receiving SNAP consumed a
      higher percentage of SSBs (65% vs. 59%, p<0.001), more calories from SSB per
      capita (210 kcal vs. 175 kcal, p=0.001), and more daily calories from SSBs among
      drinkers (307 kcal vs. 278 kcal, p=0.008). Overall, per capita consumption from
      SSBs was highest among adults receiving SNAP (210 kcal, 9% total daily intake),
      followed by adults eligible but not participating in SNAP (192 kcal, 8% total
      daily intake)--both of which had significantly higher SSB consumption than
      ineligible adults (175 kcal, 8% total daily intake) (p<0.05). CONCLUSION: Adults
      eligible for SNAP benefits consume more SSBs than ineligible adults.

PMID- 24128953
TI  - New York pharmacists push for CDTM.

PMID- 24128958
TI  - Validity and reliability of a practitioner service tool: potential resource for
      assessing faculty practitioners.

PMID- 24128957
TI  - A telepharmacy intervention to improve inhaler adherence in veterans with chronic
      obstructive pulmonary disease.

PMID- 24128959
TI  - Effect of simvastatin-amiodarone drug interaction alert on appropriate
      prescribing.

PMID- 24128960
TI  - Workshop on the challenges in substitution of nonbiological complex drugs.

PMID- 24128961
TI  - An interdisciplinary approach to determine schistosomiasis prevalence and
      administer praziquantel to school-age children in Tanzania.

PMID- 24128963
TI  - Role of executive coaching in pharmacy management.

PMID- 24128964
TI  - Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic
      colorectal cancer.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, and
      administration of ziv-aflibercept in combination therapy for metastatic
      colorectal cancer (mCRC) are reviewed. SUMMARY: Ziv-aflibercept (Zaltrap,
      Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion
      protein that targets the angiogenesis signaling pathway of tumor cells by
      blocking vascular endothelial growth factor (VEGF) receptors that play a key role
      in tumor growth and metastasis; it is a more potent VEGF blocker than
      bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for
      use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI
      regimen) for second-line treatment of patients with mCRC who have disease
      progression during first-line oxaliplatin-based chemotherapy. A Phase III trial
      demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept
      was associated with significantly improved patient response, overall survival,
      and progression-free survival in patients with good performance status at
      baseline, including some who had received prior bevacizumab therapy. The most
      common grade 3 or 4 adverse effects associated with ziv-aflibercept use in
      clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product
      labeling warns of potential hemorrhage and other treatment-related risks.
      CONCLUSION: Current clinical data are insufficient to directly compare ziv
      aflibercept and bevacizumab when used with standard combination chemotherapy as
      first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently
      limited to the second-line setting in combination with irinotecan-based regimens
      in mCRC patients who have not received irinotecan previously. The role of ziv
      aflibercept in chemotherapy for other tumor types is yet to be determined.

PMID- 24128965
TI  - Impact of implementing smart infusion pumps in a pediatric intensive care unit.
AB  - PURPOSE: The impact of smart infusion pumps on the interception of errors in the
      programming of i.v. drug administrations on a pediatric intensive care unit
      (PICU) is investigated. METHODS: A prospective observational intervention study
      was conducted in the PICU of a hospital in Madrid, Spain, to estimate the patient
      safety benefits resulting from the implementation of smart pump technology
      (Alaris System, CareFusion, San Diego, CA). A systematic analysis of data stored
      by the devices during the designated study period (January 2010-June 2011) was
      conducted using the system software (Guardrails CQI Event Reporter, CareFusion).
      The severity of intercepted errors was independently classified by a group of
      four clinical pharmacists and a group of four intensive care pediatricians;
      analyses of intragroup and intergroup agreement in perceptions of severity were
      performed. RESULTS: During the 17-month study period, the overall rate of user
      compliance with the safety software was 78%. The use of smart pump technology
      resulted in the interception of 92 programming errors, 84% of which involved
      analgesics, antiinfectives, inotropes, and sedatives. About 97% of the errors
      resulted from user programming of doses or infusion rates above the hard limits
      defined in the smart pump drug library. The potential consequences of the
      intercepted errors were considered to be of moderate, serious, or catastrophic
      severity in 49% of cases. CONCLUSION: The use of smart pumps in a PICU improved
      patient safety by enabling the interception of infusion programming errors that
      posed the potential for severe injury to pediatric patients.

PMID- 24128966
TI  - Evaluation and use of a rapid Staphylococcus aureus assay by an antimicrobial
      stewardship program.
AB  - PURPOSE: The performance of a rapid test for methicillin-resistant Staphylococcus
      aureus (MRSA) in a large community hospital was investigated. METHODS: A
      prospective observational study was conducted to evaluate an
      immunochromatographic assay (Alere PBP2a Culture Colony Test, Alere Scarborough,
      Inc.) for rapid differentiation of MRSA and methicillin-susceptible S. aureus
      (MSSA) strains using isolates cultured overnight on common laboratory media. S.
      aureus isolates cultured for 12-24 hours were tested with the assay, which
      detects penicillin-binding protein 2a (PBP2a) and provides results in six
      minutes. The test results were compared with data from standard overnight
      antimicrobial susceptibility testing to determine the assay's sensitivity and
      specificity. Changes in therapy associated with use of the rapid assay were
      evaluated. RESULTS: Over an 11-month period, 661 inpatient isolates from mostly
      nonhematologic sites were tested. There were six false-negative results,
      indicating assay sensitivity of 98.4%, with no false positives (specificity of
      100%). Eight invalid test results were documented. During designated evaluation
      periods, a total of 169 patient cases involving PBP2a testing were reviewed by
      the hospital's antimicrobial stewardship pharmacist. In 63 of those cases (37%),
      changes in therapy were implemented on the day of test result posting.
      Interventions often involved switching patients from inappropriate to appropriate
      MRSA therapy or optimizing MRSA- or MSSA-targeted therapy. CONCLUSION: An assay
      for quickly differentiating between MRSA and MSSA was highly sensitive, highly
      specific, and inexpensive in actual hospital use and led to rapid prescription of
      appropriate antistaphylococcal therapy 24-48 hours after culture specimens were
      collected.

PMID- 24128968
TI  - Significant publications on infectious diseases pharmacotherapy in 2012.
AB  - PURPOSE: The most important articles pertaining to infectious diseases (ID)
      pharmacotherapy published in 2012, as nominated and ranked by panels of
      pharmacists and physicians with ID expertise, are summarized. SUMMARY: Members of
      the Houston Infectious Diseases Network were asked to nominate articles on ID
      research published in prominent peer-reviewed journals during the period January
      1-December 31, 2012, with a major impact in the field of ID pharmacotherapy. A
      list of 42 nominated articles on general ID-related topics and 8 articles
      pertaining to human immunodeficiency virus (HIV) infection or acquired
      immunodeficiency syndrome (AIDS) was compiled. In a survey conducted in January
      2013, members of the Society of Infectious Diseases Pharmacists (SIDP) were asked
      to select from the list 10 general ID articles and 1 HIV/AIDS-related article
      that they considered to be the most important. Of the 180 SIDP members surveyed,
      100 (55%) and 44 (24%) participated in ranking the general ID and HIV/AIDS
      related articles, respectively. Summaries of the highest-ranked articles in both
      categories are presented here. CONCLUSION: With the volume of published ID
      related research growing each year, both ID specialists and nonspecialists are
      challenged to stay current with the literature. Key ID-related publications in
      2012 included updated recommendations on management of diabetic foot infections,
      articles on promising approaches to prevention and early treatment of HIV
      disease, and reports on developments in research on pharmacotherapies for
      methicillin-resistant Staphylococcus aureus bacteremia and Klebsiella pneumoniae
      infections.

PMID- 24128967
TI  - Management of bleeding and reversal strategies for oral anticoagulants: clinical
      practice considerations.
AB  - PURPOSE: Currently available clinical data and optimal strategies for reversing
      oral anticoagulants in patients who are bleeding or need an urgent invasive
      procedure or operation are reviewed. SUMMARY: Bleeding from oral anticoagulants,
      including new target-specific oral agents (TSOAs), is a common cause of morbidity
      and mortality, especially in elderly patients. Limited clinical data are
      available to guide the reversal of warfarin or TSOAs in patients who are bleeding
      or need an urgent invasive procedure or operation. A panel of five experts with
      diverse backgrounds in anticoagulation therapy, cardiology, critical care, and
      emergency medicine and with experience in managing complications of
      anticoagulation therapy was convened to develop practical strategies for managing
      patients receiving oral anticoagulants who are bleeding or have an urgent need
      for an invasive procedure. The strategies were designed to guide clinicians in
      the acute care setting by providing efficient and potentially effective
      management concepts to avoid delays in initiating treatment that could adversely
      affect patient outcomes. The consensus of this expert panel is summarized herein.
      Recommendations are based on currently available evidence from a comprehensive
      review of the literature and other pertinent data, along with the experience and
      expert opinion of the panelists. CONCLUSION: Bleeding is a serious complication
      of the use of oral anticoagulants, and limited information is available to guide
      the reversal of warfarin or TSOAs in patients who are bleeding or are in need of
      an urgent invasive procedure. Use of a systematic approach to assessing and
      treating these patients based on available evidence and expert opinion can help
      avoid delays that could adversely affect patient outcomes.

PMID- 24128969
TI  - Evaluating promotional claims as false or misleading.
AB  - In light of the "false or misleading" standard resulting from the recent legal
      ruling, it can be concluded that a true claim is one that is both factually and
      analytically true. Factual truth could be based on the accuracy of the
      information and the sufficiency of the information. Analytical truth could be
      based on the scientific foundation for the claim and whether the information
      within the claim is presented in a balanced way. Regarding the assessment of
      whether a truthful claim is misleading, the evaluator could consider the
      relevance, consistency, and context of the information. Standards are important
      in medication use and medication regulation. Health care professionals who must
      decide whether a claim is truthful and not misleading will rely on guidance from
      FDA in determining how to evaluate promotional claims. As the court suggested in
      the case reviewed here, FDA could take the lead and provide guidance "in
      differentiating between misleading and false promotion, exaggerations and
      embellishments, and truthful or non-misleading information." Existing FDA
      regulations provide a foundation for such guidance. The next step for the agency
      would be to expand existing guidance to specifically describe how an off-label
      claim can be identified as either false or misleading.

PMID- 24128971
TI  - Assessment of myocardial function in preterm infants with patent ductus
      arteriosus using tissue Doppler imaging.
AB  - OBJECTIVE: To assess myocardial function in preterm infants with different
      degrees of ductal patency in the first week of life using tissue Doppler imaging.
      STUDY DESIGN: Infants <30 weeks of gestation underwent echocardiography on day 3.
      A total of 72 infants were recruited into the study and categorised into three
      groups (i) haemodyamically significant ductus arteriosus, (ii) patent ductus
      arteriosus and (iii) no patent ductus arteriosus. Those with haemodynamically
      significant ductus arteriosus were treated with indometacin and echocardiography
      was repeated after 48-72 hours following treatment. Peak systolic and diastolic
      myocardial velocities were obtained using tissue Doppler imaging, and myocardial
      performance index was calculated. RESULTS: Initial myocardial velocities were
      significantly lower and myocardial performance index significantly higher in the
      haemodynamically significant ductus arteriosus group compared with other groups.
      For the haemodynamically significant ductus arteriosus group, post-treatment
      myocardial velocities were higher and myocardial performance index lower than pre
      treatment. CONCLUSION: Preterm infants with haemodynamically significant ductus
      arteriosus had lower myocardial velocities and higher myocardial performance
      index, suggesting relative systolic and diastolic myocardial dysfunction. Babies
      whose patent ductus arteriosus remained open despite indometacin had lower pre
      treatment myocardial velocities and higher myocardial performance index than
      those babies whose patent ductus arteriosus closed, suggesting worse myocardial
      function in this group. Measurement of myocardial function using tissue Doppler
      imaging in preterm infants is feasible and may prove to be helpful in the
      management of babies with patent ductus arteriosus.

PMID- 24128972
TI  - The role of the agricultural matrix: coffee management and euglossine bee
      (Hymenoptera: Apidae: Euglossini) communities in southern Mexico.
AB  - With growing concern surrounding global pollinator declines, it is important to
      understand how habitat destruction and agricultural intensification impact
      pollinator communities. Euglossine bees are tropical forest-dependent pollinators
      responsible for pollination of both economically important crops and wild plant
      species. A growing body of work has focused on the effect of habitat
      fragmentation on euglossine bees, yet little is known about how these bees are
      impacted by agricultural intensification. Coffee cultivation is widespread in the
      tropics, and its management is conducted along a gradient of intensity, which
      ranges from monoculture (i.e., no shade, high inputs) to polyculture (shade
      overstory retained, fewer inputs). We used a landscape in Soconusco, Chiapas,
      Mexico, that allowed for comparison between monoculture and polyculture coffee
      farms, while holding distance to native habitat, as well as native habitat
      quality, constant. We found that habitat management influenced abundance,
      estimated richness, and community composition of euglossine bees. The polyculture
      coffee farm boasts a more similar community composition to the forest than to the
      monoculture coffee farm. In addition, the polyculture farm had almost double the
      euglossine abundance compared with the monoculture farm. Our results suggest that
      coffee management regimes may strongly impact euglossine communities and that
      less intensive polyculture approaches may mitigate species losses of this
      important group of pollinators. 

PMID- 24128970
TI  - Lipid abnormalities and lipid-based repair strategies in atopic dermatitis.
AB  - Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation,
      IgE production, mast cell hyperactivity, and dendritic cell signaling in the
      evolution of the chronic, pruritic, inflammatory dermatosis that characterizes
      atopic dermatitis (AD). We review here increasing evidence that the inflammation
      in AD results primarily from inherited abnormalities in epidermal structural and
      enzymatic proteins that impact permeability barrier function. We also will show
      that the barrier defect can be attributed to a paracellular abnormality due to a
      variety of abnormalities in lipid composition, transport and extracellular
      organization. Accordingly, we also review the therapeutic implications of this
      emerging pathogenic paradigm, including several current and potentially novel,
      lipid-based approaches to corrective therapy. This article is part of a Special
      Issue entitled The Important Role of Lipids in the Epidermis and their Role in
      the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R.
      Feingold and Peter Elias. 

PMID- 24128973
TI  - Plateletcrit may not be a useful predictor in patients with slow coronary flow.

PMID- 24128975
TI  - Anorexia of aging: a modifiable risk factor for frailty.
AB  - Anorexia of aging, defined as a loss of appetite and/or reduced food intake,
      affects a significant number of elderly people and is far more prevalent among
      frail individuals. Anorexia recognizes a multifactorial origin characterized by
      various combinations of medical, environmental and social factors. Given the
      interconnection between weight loss, sarcopenia and frailty, anorexia is a
      powerful, independent predictor of poor quality of life, morbidity and mortality
      in older persons. One of the most important goals in the management of older,
      frail people is to optimize their nutritional status. To achieve this objective
      it is important to identify subjects at risk of anorexia and to provide multi
      stimulus interventions that ensure an adequate amount of food to limit and/or
      reverse weight loss and functional decline. Here, we provide a brief overview on
      the relevance of anorexia in the context of sarcopenia and frailty. Major
      pathways supposedly involved in the pathogenesis of anorexia are also
      illustrated. Finally, the importance of treating anorexia to achieve health
      benefits in frail elders is highlighted. 

PMID- 24128974
TI  - Adiponectin: an attractive marker for metabolic disorders in Chronic Obstructive
      Pulmonary Disease (COPD).
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung
      disease which may be complicated by development of co-morbidities including
      metabolic disorders. Metabolic disorders commonly associated with this disease
      contribute to lung function impairment and mortality. Systemic inflammation
      appears to be a major factor linking COPD to metabolic alterations. Adipose
      tissue seems to interfere with systemic inflammation in COPD patients by
      producing a large number of proteins, known as "adipokines", involved in various
      processes such as metabolism, immunity and inflammation. There is evidence that
      adiponectin is an important modulator of inflammatory processes implicated in
      airway pathophysiology. Increased serum levels of adiponectin and expression of
      its receptors on lung tissues of COPD patients have recently highlighted the
      importance of the adiponectin pathway in this disease. Further, in vitro studies
      have demonstrated an anti-inflammatory activity for this adipokine at the level
      of lung epithelium. This review focuses on mechanisms by which adiponectin is
      implicated in linking COPD with metabolic disorders. 

PMID- 24128976
TI  - Lateral medullary stroke in patient with granulomatous polyangiitis.
AB  - Granulomatous polyangiitis (GPA), also known as Wegener granulomatosis, is a
      systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis that
      infrequently affects the central nervous system. We report a 41-year-old man with
      lateral medullary infarction who developed rapidly progressive renal failure. He
      was diagnosed with GPA based on positive serum c-ANCA and antiproteinase 3
      antibodies and demonstration of pauci-immune crescentic glomerulonephritis on
      kidney biopsy. He was treated with Coumadin, pulse steroids, cyclophosphamide,
      and plasmapheresis. He had resolution of his neurologic deficits and improvement
      in renal function. This case report highlights the importance to consider GPA
      vasculitis in the differential diagnosis of stroke in patients with development
      of acute kidney injury. 

PMID- 24128977
TI  - Post-mastectomy breast reconstruction.

PMID- 24128978
TI  - Encephalitis claims 13 more lives as Indian government launches vaccine against
      one cause of the outbreak.

PMID- 24128979
TI  - Transverse ultrasound through the thyroid gland.

PMID- 24128980
TI  - Researchers recommend routine HIV testing for patients in Indian hospitals.

PMID- 24128981
TI  - GP-led service helped seven in 10 patients avoid long term sickness absence.

PMID- 24128982
TI  - Only five out of 19 maternity units in Ireland are following recent advice,
      report finds.

PMID- 24128983
TI  - Six Gulf states consider introducing checks of sex of immigrant workers.

PMID- 24128984
TI  - Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia--the
      case in favour.
AB  - Bronchopulmonary dysplasia (BPD) is a major sequel of extremely premature birth.
      Multiple ante- and postnatal factors act in concert to injure the immature lung
      in the pathogenesis of the disease. Among them, chorioamnionitis--according to
      current evidence--plays a pivotal role. Pulmonary inflammatory processes seen in
      animal models of chorioamnionitis resemble those seen in premature infants who
      developed BPD. Chorioamnionitis can doubtlessly induce extremely preterm birth,
      thus contributing to a gestation-dependent risk of BPD. A gestation-independent
      association of chorioamnionitis with an increased risk of developing BPD has been
      demonstrated by a recent systematic review of clinical observational studies.
      Antenatal inflammation with signs of a systemic fetal response reduces the
      response to exogenous surfactant in infants with respiratory distress syndrome,
      leading to a longer need for mechanical ventilation. Moreover, chorioamnionitis
      increases the risk of early onset sepsis. Both mechanical ventilation and sepsis
      are, however, major postnatal risk factors for BPD.

PMID- 24128986
TI  - Recent and new targets for small molecule anti-cancer agents.

PMID- 24128985
TI  - Non-protein therapeutics.

PMID- 24128987
TI  - A biological stabilization technology for peptide drugs: enzymatic introduction
      of thioether-bridges.

PMID- 24128988
TI  - HIV-derived peptide mimics.

PMID- 24128989
TI  - Toward multivalent carbohydrate drugs.

PMID- 24128990
TI  - Switchable peptides.

PMID- 24128991
TI  - Widowhood, age heterogamy, and health: the role of selection, marital quality,
      and health behaviors.
AB  - OBJECTIVE: Although the impact of widowhood on the surviving spouse's health has
      been widely documented, there is little empirical research examining whether
      certain spousal choice decisions and marital sorting patterns predispose
      individuals to be more vulnerable to the adverse consequences of widowhood for
      health. DESIGN AND METHOD: We use data from the Wisconsin Longitudinal Study and
      employ ordinary least squares models to (a) document variations in mental and
      physical health between married and widowed persons, (b) determine whether
      widowed persons in age heterogamous unions are especially vulnerable to the
      adverse consequences of widowhood, and (c) investigate to what extent
      differential selection, marital quality, and health practices account for health
      disparities by marital status and the spousal age gap. RESULTS: Widowed persons,
      especially those in age heterogamous unions, have worse mental health than
      married persons, but they do not seem to be more disadvantaged in terms of
      physical health. Differential selection, marital quality, and health behaviors
      partly account for some of the health disparities by marital status and spousal
      age gap. DISCUSSION: Our findings suggest that marrying a spouse who is very
      dissimilar in age may enhance one's vulnerability to the adverse consequences of
      widowhood for health.

PMID- 24128992
TI  - In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129
      alpha-synuclein phosphorylation in mouse brain.
AB  - alpha-Synuclein is the major component of Lewy bodies. alpha-Synuclein
      phosphorylated at Ser 129 (Phospho-alpha-Syn) is the most common synuclein
      modification observed in Parkinson's disease pathology and transgenic animal
      models. Polo-like kinase 2 (PLK2) was previously proposed as an important kinase
      in alpha-synuclein phosphorylation at Ser129. To better understand the role of
      PLK2 in alpha-synuclein phosphorylation in vivo, we further evaluated the effect
      of PLK2 genetic knockdown and pharmacological inhibition on Phospho-alpha-Syn
      levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and
      wild-type (WT) mice. Whereas PLK2 knockdown had no effect on Total-alpha
      synuclein brain levels, it resulted in a gene-dosage dependent, albeit
      incomplete, reduction of endogenous Phospho-alpha-Syn levels in all brain regions
      investigated. No compensatory induction of other alpha-synuclein kinases (PLK3,
      casein kinase-2, G-protein-coupled receptor kinase 5 (GRK5) and GRK6) was
      observed at the mRNA level in the PLK2 KO mouse brain. To determine whether
      increased activity of another PLK family member is responsible for the residual
      Phospho-alpha-Syn levels in the PLK2 KO mouse brain, the pan-PLK inhibitor BI
      2536 was tested in PLK2 KO mice. Whereas BI 2536 reduced Phospho-alpha-Syn levels
      in WT mice, it did not further reduce the residual endogenous Phospho-alpha-Syn
      levels in PLK2 KO and Het mice, suggesting that a kinase other than PLK1-3
      accounts for the remaining PLK inhibitor-resistant pool in the mouse brain.
      Moreover, PLK3 KO in mice had no effect on both Total- and Phospho-alpha-Syn
      brain levels. These results support a significant role for a PLK kinase in
      phosphorylating alpha-synuclein at Ser129 in the brain, and suggest that PLK2 is
      responsible for this activity under physiological conditions. 

PMID- 24128993
TI  - Inflammation and iron metabolism in adult patients with epilepsy: does a link
      exist?
AB  - PURPOSE: Inflammation has been shown to play a key role in epilepsy, and may also
      affect both the iron status and metabolism. Consequently, a relationship between
      iron metabolism and neuronal excitability and seizures could be expected.
      METHODS: We aimed at characterizing in 37 adult patients affected by focal
      epilepsy during the interictal period serum inflammatory cytokines, such as
      interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1
      receptor-antagonist (IL-1RA), tumor necrosis factor-alpha (TNF-alpha), and
      markers of iron status and metabolism: hemoglobin concentration (Hgb), mean
      corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron
      and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic
      activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase
      activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and
      ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations
      between these biological markers as well their relationship with patients'
      clinical features. A group of 43 healthy subjects had the same serologic
      measurements to serve as controls. RESULTS: Our findings showed in the group of
      patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-alpha
      (p=0.002) with respect to healthy subjects. For the first time, we also detected
      significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a
      decrease of Tf (p=0.031), possibly driven by cytokine modifications and
      consistent with inflammation as acute phase and antioxidant activity markers.
      Accordingly, TNF-alpha positively correlated with Tf (p=0.005). Finally, a
      significant positive correlation between seizures frequency and eCp (p=0.046) and
      inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation
      between TNF-alpha and the duration of epilepsy (p=0.021) was detected.
      CONCLUSIONS: Our findings demonstrate a relevant relationship between epilepsy
      and systemic inflammation, with a consistent link between seizures, inflammatory
      cytokines (IL-6 and TNF-alpha) and iron regulation and metabolism, as acute phase
      and antioxidant markers.

PMID- 24128994
TI  - Two-dimensional echocardiographic predictors of coarctation of the aorta.
AB  - BACKGROUND: Coarctation of the aorta is a very common congenital heart
      malformation. It is frequently associated with other abnormalities.
      Echocardiography is the diagnostic modality for congenital heart disease. The
      carotid-subclavian artery index and the isthmus/descending aorta index were
      proposed for establishing the diagnosis of coarctation of the aorta. OBJECTIVES:
      The objectives were to evaluate such indexes and to look for other
      echocardiographic predictors of coarctation of the aorta. METHOD:
      Echocardiography was reviewed for infants with coarctation of the aorta, as well
      as a control group, using the Echo PAC Dimension. Standard measurements were
      obtained from different sites of the aortic arch. RESULTS: A total of 31 infants
      3 months or less with coarctation of the aorta and 50 infants with no coarctation
      of the aorta were reviewed. Abnormal aortic valve was present in 65% of those
      with coarctation of the aorta. The diameters of the proximal and the distal
      transverse aortic arch were smaller in the coarctation of the aorta group. The
      distance between the aortic arch branches was longer in the coarctation of the
      aorta group. Apart from the ratio between distance 2 and the ascending aorta,
      other ratios/indexes were smaller in the coarctation of the aorta group than in
      the control group. CONCLUSION: The presence of abnormal aortic valve, a carotid
      subclavian index <1.1, I/AAo ratio <0.53, and DTA/AAo ratio <0.6 suggest the
      presence of coarctation of the aorta. Neonates with large patent ductus
      arteriosus and any of these findings need close observation until the patent
      ductus arteriosus closes. If the arch is difficult to assess by two-dimensional
      echocardiography, the patient may need further imaging to rule out coarctation of
      the aorta.

PMID- 24128995
TI  - How people with serious mental illness seek help after leaving jail.
AB  - In this study, I examined how people with serious mental illness defined and
      prioritized their service needs when released from jail and how these service
      priorities shaped the sequencing of help-seeking activities after their release.
      Data included ethnographic observations and interviews with the staff and clients
      of a mental health reentry program and responses to an open-ended questionnaire
      that was given to the program's clients (N = 115). Sixty-three percent of the
      clients identified housing and 35% identified financial assistance as one of
      their two most important service needs, whereas only 12% selected treatment
      services. These service priorities reflect a hierarchy in help-seeking activities
      postrelease in which clients' access to treatment services was predicated on
      their ability to first find sustainable economic and material support. I conclude
      that reentry programs need to have the resources required to meet both the basic
      and treatment needs of people with serious mental illness leaving jail. 

PMID- 24128996
TI  - A prospective, randomized, controlled, double-masked, multi-center clinical trial
      of medical adhesives for the closure of laparoscopic incisions.
AB  - STUDY OBJECTIVE: To compare LiquiBand Surgical S (LB) (Advanced Medical Solutions
      Ltd, Plymouth, UK) with High Viscosity Dermabond (DB) (Ethicon Inc., Kirkland,
      Scotland) for the closure of laparoscopic wounds. DESIGN: Prospective,
      multicenter, randomized, controlled trial (Canadian Task Force classification I).
      SETTING: Multiple district hospitals. PARTICIPANTS: A total of 433 subjects were
      enrolled between 2006 and 2009 at 4 investigational sites. INTERVENTIONS: In this
      study, LB, an octyl/butyl cyanoacrylate blend, and DB, an octyl-based
      cyanoacrylate, were compared for topical skin closure of laparoscopic port sites
      (www.clinicaltrials.gov; study identifier NCT00762905). MAIN RESULTS: High dermal
      apposition and cosmesis scores resulted from the use of both adhesives along with
      low rates of wound dehiscence and suspected infections. Masked evaluators and
      patients favored DB in the healing of the incisions (98.3% DB vs 93.9% LB, p <
      .05) and (97.2% DB vs 89.4% LB, p < .05). However, there was no difference in the
      overall satisfaction of the appearance of the wounds. LB was found to be
      significantly (p < .05) faster (LB = 32.1 seconds; DB, 50.3 seconds) and easier
      to use than DB, and surgical users were significantly more satisfied with using
      LB for wound closure. CONCLUSION: The results of this trial show the efficacy of
      LB for the closure of topical skin incisions; LB was significantly faster, easier
      to use, and resulted in greater user satisfaction compared with DB.

PMID- 24128997
TI  - Alcohol and type 1 diabetes: Patient knowledge of alcohol-induced sustained
      hypoglycaemia.

PMID- 24128998
TI  - Closed loop developments to improve glucose control at home.
AB  - Insulin delivery in a closed-loop mode has been a dream for many patients with
      insulin-treated diabetes since bedside artificial pancreas (AP) systems were
      developed in the 1970s. Beside safe near-normal glucose levels, the goal of AP is
      to alleviate patients' burden and fear of continual adjustment of insulin
      delivery needed to cope with daily activities and events. Portable pumps using
      subcutaneous (SC) insulin infusion and 'needle-type' enzymatic sensors allowing
      continuous glucose monitoring (CGM) in the interstitial SC fluid are typically
      used in the current AP prototypes. Model predictive control algorithms which take
      into account the delays inherent with SC insulin infusion and glucose sensing
      have shown improved glucose control in hospital setting. Currently, pilot trials
      are performed in home-like conditions to assess the technical feasibility, safety
      and efficacy of glucose control, and patients' ability to manage AP. Recently
      developed wearable smart phone-based platforms connect wirelessly to the insulin
      pump and the CGM, run control algorithms, provide online information to/from the
      patient, and allow remote monitoring reaching a new frontier - first outpatient
      experiments. The future holds expansion of home trials supporting the approval of
      systems which could revolutionize diabetes treatment and make easier the daily
      life of patients with diabetes.

PMID- 24128999
TI  - Glucose variability: An emerging target for the treatment of diabetes mellitus.
AB  - Alterations in glucose metabolism in individuals with diabetes have been
      considered for many years, as they appear at first glance, i.e., simply as
      hyperglycemia, and its surrogate marker, glycated hemoglobin (HbA1c), used both
      to estimate the risk of developing diabetic complications and to define the
      targets and measure the efficacy of diabetes treatments. However, over time
      diabetes-related glycemic alterations have been considered in more complex terms,
      by attempting to identify the role of fasting glycemia, postprandial glycemia and
      hypoglycemia in the overall assessment of the disease. This set of evaluations
      has led to the concept of glucose variability. Although intuitively easy to
      understand, it cannot be equally simply translated into terms of definition,
      measuring, prognostic and therapeutic impact. The literature available on glucose
      variability is extensive yet confused, with the only common element being the
      need to find out more on the subject. The purpose of this manuscript is not only
      to review the most recent evidence on glucose variability, but also to help the
      reader to better understand the available measurement options, and how the
      various definitions can differently be related with the development of diabetic
      complications. Finally, we provide how new and old drugs can impact on glucose
      variability.

PMID- 24129000
TI  - Atrazine leaching from biochar-amended soils.
AB  - The herbicide atrazine is used extensively throughout the United States, and is a
      widespread groundwater and surface water contaminant. Biochar has been shown to
      strongly sorb organic compounds and could be used to reduce atrazine leaching. We
      used lab and field experiments to determine biochar impacts on atrazine leaching
      under increasingly heterogeneous soil conditions. Application of pine chip
      biochar (commercially pyrolyzed between 300 and 550  degrees C) reduced
      cumulative atrazine leaching by 52% in homogenized (packed) soil columns
      (p=0.0298). Biochar additions in undisturbed soil columns did not significantly
      (p>0.05) reduce atrazine leaching. Mean peak groundwater atrazine concentrations
      were 53% lower in a field experiment after additions of 10 t ha(-1) acidified
      biochar (p=0.0056) relative to no biochar additions. Equivalent peat applications
      by dry mass had no effect on atrazine leaching. Plots receiving a peat-biochar
      mixture showed no reduction, suggesting that the peat organic matter may compete
      with atrazine for biochar sorption sites. Several individual measurement values
      outside the 99% confidence interval in perched groundwater concentrations
      indicate that macropore structure could contribute to rare, large leaching events
      that are not effectively reduced by biochar. We conclude that biochar application
      has the potential to decrease peak atrazine leaching, but heterogeneous soil
      conditions, especially preferential flow paths, may reduce this impact. Long-term
      atrazine leaching reductions are also uncertain.

PMID- 24129001
TI  - Effects of four commonly used UV filters on the growth, cell viability and
      oxidative stress responses of the Tetrahymena thermophila.
AB  - UV filters are increasingly used in sunscreens and other personal care products.
      Although their residues have been widely identified in aquatic environment,
      little is known about the influences of UV filters to protozoan. The growth
      inhibition effects, cell viability and oxidative stress responses of four
      commonly used UV filters, 2-ethylhexyl 4-methoxycinnamate (EHMC), benzophenone-3
      (BP-3), 4-methyl-benzylidene camphor (4-MBC) and octocrylene (OC), to protozoan
      Tetrahymena thermophila were investigated in this study. The 24-h EC50 values
      with 95% confidence intervals for BP-3 and 4-MBC were 7.544 (6.561-8.675) mg L(
      1) and 5.125 (4.874-5.388) mg L(-1), respectively. EHMC and OC did not inhibit
      the growth of T. thermophila after 24h exposure at the tested concentrations. The
      results of cell viability assays with propidium iodide (PI) staining were
      consistent with that of the growth inhibition tests. As for BP-3 and 4-MBC, the
      relatively higher concentrations, i.e. of 10.0 and 15.0 mg L(-1), could lead to
      the cell membranes impairment after 4h exposure. With the increase of the
      exposure time to 6h, their adverse effects on cell viability of T. thermophila
      were observed at the relatively lower concentration groups (1.0 mg L(-1) and 5.0
      mg L(-1)). In addition, it is noticeable that at environmentally relevant
      concentration (1.0 MUg L(-1)), BP-3 and 4-MBC could lead to the significant
      increase of catalase (CAT) activities of the T. thermophila cells. Especially for
      the BP-3, the oxidative injuries were further confirmed by the reduction of
      glutathione (GSH) content. It is imperative to further investigate the additive
      action of UV filters and seek other sensitive endpoint, especially at
      environmentally relevant concentration.

PMID- 24129003
TI  - Improvement of functional recovery of transected peripheral nerve by means of
      chitosan grafts filled with vitamin E, pyrroloquinoline quinone and their
      combination.
AB  - Effects of vitamin E and pyrroloquinoline quinone on peripheral nerve
      regeneration were studied using a rat sciatic nerve transection model. Ninety
      male healthy White Wistar rats were divided into three experimental groups (n =
      15), randomly: Sham-operation (SHAM), transected control (TC), chitosan conduit
      (Chit) and three treatment groups (Vit E, PQQ and PQQ + Vit E). In SHAM group
      after anesthesia, left sciatic nerve was exposed through a gluteal muscle
      incision and after homeostasis muscle was sutured. In Chit group left sciatic
      nerve was exposed the same way and transected proximal to tibio-peroneal
      bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted
      into a chitosan tube. In treatment groups the tube was implanted the same way and
      filled with Vit E, PQQ and PQQ + Vit E. Each group was subdivided into three
      subgroups of six animals each and were studied 4, 8, 12 weeks after surgery.
      Functional and electrophysiological studies, and gastrocnemius muscle mass
      measurement confirmed faster and better recovery of regenerated axons in Vit E +
      PQQ combination compared to Vit E or PQQ solely (P < 0.05). Morphometric indices
      of regenerated fibers showed number and diameter of the myelinated fibers in PQQ
      + Vit E was significantly higher than in other treatment groups. In
      immunohistochemistry, location of reactions to S-100 in PQQ + Vit E was clearly
      more positive than in other treatment groups. Response to PQQ + Vit E treatment
      demonstrates that it influences and improves functional recovery of peripheral
      nerve regeneration.

PMID- 24129004
TI  - A case of prolactinoma with chordoma.

PMID- 24129002
TI  - Conjugative type IV secretion systems in Gram-positive bacteria.
AB  - Bacterial conjugation presents the most important means to spread antibiotic
      resistance and virulence factors among closely and distantly related bacteria.
      Conjugative plasmids are the mobile genetic elements mainly responsible for this
      task. All the genetic information required for the horizontal transmission is
      encoded on the conjugative plasmids themselves. Two distinct concepts for
      horizontal plasmid transfer in Gram-positive bacteria exist, the most prominent
      one transports single stranded plasmid DNA via a multi-protein complex, termed
      type IV secretion system, across the Gram-positive cell envelope. Type IV
      secretion systems have been found in virtually all unicellular Gram-positive
      bacteria, whereas multicellular Streptomycetes seem to have developed a
      specialized system more closely related to the machinery involved in bacterial
      cell division and sporulation, which transports double stranded DNA from donor to
      recipient cells. This review intends to summarize the state of the art of
      prototype systems belonging to the two distinct concepts; it focuses on protein
      key players identified so far and gives future directions for research in this
      emerging field of promiscuous interbacterial transport. 

PMID- 24129005
TI  - A case report of an ectopic clival growth hormone adenoma associated with an
      empty sella and a review of the literature.

PMID- 24129006
TI  - Interpretation of verb phrase telicity: sensitivity to verb type and determiner
      type.
AB  - PURPOSE: The authors examine how adults use linguistic information from verbs,
      direct objects, and particles to interpret an event description as encoding a
      logical endpoint to the event described (in which case, it is telic) or not (in
      which case, it is atelic). Current models of aspectual composition predict that
      quantity-sensitive verbs combined with quantized objects produce telic
      predicates. Behavioral results from previous experiments have not unequivocally
      confirmed this prediction. The study presents a more fine-grained analysis that
      examines the influence of partitive verbs, resultative particles, and different
      determiner types on listeners' evaluations of verb phrases as telic or atelic.
      METHOD: Forty-eight English-speaking adults participated in a truth-value
      judgment task to determine whether they interpreted verb phrases with different
      types of verbs and direct objects as telic or atelic. Participants viewed short
      videos and responded to a yes/no question after each one. RESULTS: The presence
      of partitive quantity-sensitive verbs and the presence of a definite determiner
      versus a cardinal number in quantized direct objects had a differential impact on
      listeners' interpretations of sentences as telic. CONCLUSION: The results
      indicate that actual behavioral interpretations of telicity are meaningfully
      influenced by the presence of partitive verbs, resultative particles, and
      different types of determiners.

PMID- 24129007
TI  - Eye-tracking measures reveal how changes in the design of aided AAC displays
      influence the efficiency of locating symbols by school-age children without
      disabilities.
AB  - PURPOSE Many individuals with communication impairments use aided augmentative
      and alternative communication (AAC) systems involving letters, words, or line
      drawings that rely on the visual modality. It seems reasonable to suggest that
      display design should incorporate information about how users attend to and
      process visual information. The organization of AAC symbols can influence the
      speed and accuracy with which children select a target symbol on a display. This
      research examined why some displays facilitate responding. METHOD Eye-tracking
      technology recorded point-of-gaze while children without disabilities engaged in
      a visual search task with 2 AAC displays. In 1 display, symbols sharing an
      internal color were clustered together. In the other display, like-colored
      symbols were distributed. Dependent measures were (a) latency to fixate on the
      target compared with distracters and (b) the number of fixations to target and
      distracters. RESULTS Participants were significantly slower to fixate on the
      target when like-colored symbols were distributed; there was a significant
      increase in the number of fixations to distracters that did not share color with
      the target. CONCLUSIONS Efficient search was related to minimizing fixations to
      nonrelevant distracters. Vulnerability to distraction can be a significant
      problem in individuals with disabilities who use AAC. Minimizing the intrusion of
      such distraction may, therefore, be of importance in AAC display design. 

PMID- 24129008
TI  - Bilinguals use language-specific articulatory settings.
AB  - PURPOSE Previous work has shown that monolingual French and English speakers use
      distinct articulatory settings, the underlying articulatory posture of a
      language. In the present article, the authors report on an experiment in which
      they investigated articulatory settings in bilingual speakers. The authors first
      tested the hypothesis that in order to sound native-like, bilinguals must use
      distinct, language-specific articulatory settings in monolingual mode. The
      authors then tested the hypothesis that in bilingual mode, a bilingual
      individual's articulatory setting is identical to the monolingual-mode setting of
      1 of his or her languages. METHOD Eight French-English bilinguals each read 90
      English and 90 French sentences, and the authors measured their interspeech
      posture (ISP) using optical tracking of the lips and jaw and ultrasound imaging
      of the tongue. RESULTS Results show that bilingual speakers who are perceived as
      native in both languages exhibit distinct, language-specific ISPs, and those who
      are not perceived as native in one or more languages do not. In bilingual mode,
      bilinguals use an ISP that is equivalent to the monolingual-mode ISP of their
      currently most used language. The most balanced bilingual used a French lip ISP
      but an English tongue-tip ISP. CONCLUSION Results support the claim that
      bilinguals who sound native in each of their languages have distinct articulatory
      settings for each language. 

PMID- 24129009
TI  - Language learning of children with typical development using a deductive
      metalinguistic procedure.
AB  - PURPOSE In the current study, the author aimed to determine whether 4- to 6-year
      old typically developing children possess requisite problem-solving and language
      abilities to produce, generalize, and retain a novel verb inflection when taught
      using an explicit, deductive teaching procedure. METHOD Study participants
      included a cross-sectional sample of 4-, 5-, and 6-year-old children with typical
      cognitive and language development. The 66 participants were randomly assigned to
      either a deductive or inductive teaching condition in which they were taught a
      novel gender morphological inflection across 4 sessions. Learning was assessed on
      the basis of performance on learning, generalization, and maintenance probes.
      RESULTS Across all age groups, children were more likely to successfully use the
      novel gender form when taught using the deductive procedure than if taught using
      the inductive procedure (Phi range: .33-.73). Analyses within each age group
      revealed a robust effect for the 5-year-old children, with less consistent
      effects across the other age groups. CONCLUSIONS Study results suggest that 4- to
      6-year-old children with typical language and cognitive abilities are able to
      make use of a deductive language teaching procedure when learning a novel gender
      inflection. Evidence also suggests that this effect is driven by expressive and
      receptive language ability. 

PMID- 24129010
TI  - Lipreading in school-age children: the roles of age, hearing status, and
      cognitive ability.
AB  - PURPOSE The study addressed three research questions: Does lipreading improve
      between the ages of 7 and 14 years? Does hearing loss affect the development of
      lipreading? How do individual differences in lipreading relate to other
      abilities? METHOD Forty children with normal hearing (NH) and 24 with hearing
      loss (HL) were tested using 4 lipreading instruments plus measures of perceptual,
      cognitive, and linguistic abilities. RESULTS For both groups, lipreading
      performance improved with age on all 4 measures of lipreading, with the HL group
      performing better than the NH group. Scores from the 4 measures loaded strongly
      on a single principal component. Only age, hearing status, and visuospatial
      working memory were significant predictors of lipreading performance. CONCLUSIONS
      Results showed that children's lipreading ability is not fixed but rather
      improves between 7 and 14 years of age. The finding that children with HL lipread
      better than those with NH suggests experience plays an important role in the
      development of this ability. In addition to age and hearing status, visuospatial
      working memory predicts lipreading performance in children, just as it does in
      adults. Future research on the developmental time-course of lipreading could
      permit interventions and pedagogies to be targeted at periods in which
      improvement is most likely to occur. 

PMID- 24129011
TI  - Comparison of vocal loading parameters in kindergarten and elementary school
      teachers.
AB  - PURPOSE Although a global picture exists of teachers' voice demands in general,
      few studies have compared specific groups of teachers to determine whether some
      are more at risk than others. This study compared the vocal loadings of
      kindergarten and elementary school teachers; professional and nonprofessional
      vocal load were determined for both groups. METHOD Twelve kindergarten and 20
      elementary school female teachers without voice problems were monitored during 1
      workweek using the Ambulatory Phonation Monitor. Vocal loading parameters
      analyzed were F0, SPL, time dose, distance dose, and cycle dose. RESULTS
      Comparisons between the groups showed significantly higher cycle dose and
      distance dose for kindergarten teachers than for elementary school teachers, in
      both professional and nonprofessional environments. Professional and
      nonprofessional voice use comparisons showed significant differences for all
      parameters, indicating that vocal load was higher in the professional environment
      for both groups. CONCLUSIONS The higher vocal doses measured in kindergarten
      teachers suggest that particular attention should be paid to this specific group
      of teachers. Although nonprofessional vocal load is lower than professional vocal
      load, it is important to take both into account because of their cumulative
      effects. 

PMID- 24129012
TI  - Assessing gestures in young children with autism spectrum disorder.
AB  - PURPOSE The purpose of this study was to determine whether scoring of the
      gestures point,give, and show were correlated across measurement tools used to
      assess gesture production in children with an autism spectrum disorder (ASD).
      METHOD Seventy-eight children with ASD between the ages of 23 and 37 months
      participated. Correlational analyses were conducted to determine whether
      performance of 3 key gestures related to joint attention and behavior regulation
      (point, give, show) were correlated across 3 different measurement tools: the
      Autism Diagnostic Observation Schedule, the Early Social Communication Scale, and
      the MacArthur-Bates Communicative Development Inventory: Words and Gestures. To
      establish whether different measures were related at different points in
      development, children were subdivided into 2 groups based on their expressive
      language levels. RESULTS The scoring of gesture performance was not entirely
      consistent across assessment methods. The score that a child received appeared to
      be influenced by theoretical perspective, gesture definition, and assessment
      methodology, as well as developmental level. CONCLUSION When assessing the
      gestures of children with ASD, clinicians should determine what aspects of
      gesture they are interested in profiling, gather data from multiple sources, and
      consider performance in light of the measurement tool. 

PMID- 24129013
TI  - Nasal and oral inspiration during natural speech breathing.
AB  - PURPOSE: The purpose of this study was to determine the typical pattern for
      inspiration during speech breathing in healthy adults, as well as the factors
      that might influence it. METHOD: Ten healthy adults, 18-45 years of age,
      performed a variety of speaking tasks while nasal ram pressure, audio, and video
      recordings were obtained. Inspirations were categorized as nasal-only, oral-only,
      simultaneous nasal and oral, or alternating nasal and oral inspiration. The
      method was validated using nasal airflow, oral airflow, audio, and video
      recordings for 2 participants. RESULTS: The predominant pattern was simultaneous
      nasal and oral inspirations for all speaking tasks. This pattern was not affected
      either by the nature of the speaking task or by the phonetic context surrounding
      the inspiration. The validation procedure confirmed that nearly all inspirations
      during counting and paragraph reading were simultaneous nasal and oral
      inspirations, whereas for sentence reading, the predominant pattern was
      alternating nasal and oral inspirations across the 3 phonetic contexts.
      CONCLUSIONS: Healthy adults inspire through both the nose and mouth during
      natural speech breathing. This pattern of inspiration is likely beneficial in
      reducing pathway resistance while preserving some of the benefits of nasal
      breathing.

PMID- 24129014
TI  - Delayed Stimulus-Specific Improvements in Discourse Following Anomia Treatment
      Using an Intentional Gesture.
AB  - Purpose: In this study, the authors assessed how the addition of intentional left
      hand gestures to an intensive treatment for anomia affects 2 types of discourse:
      picture description and responses to open-ended questions.Method: Fourteen people
      with aphasia completed treatment for anomia comprising 30 treatment sessions over
      3 weeks.Seven subjects also incorporated intentional left-hand gestures into each
      treatment trial.Results: Both groups demonstrated significant changes in trained
      items and improved naming of untrained items but no change in Western Aphasia
      Battery-Aphasia Quotient(WAB-AQ; Kertesz, 1982) scores. Changes in discourse were
      limited to the 3-month follow-up assessment. Several discourse measures showed
      significant improvements in the picture description task and declines during
      question responses. Additionally, the gesture group produced more words at each
      assessment, whereas the no gesture group produced fewer words at each assessment.
      These patterns led to improvements in picture descriptions and minimal declines
      in question responses in the gesture group. In contrast, the no gesture group
      showed minimal improvements in picture descriptions and production declines in
      question responses relative to pretreatment levels.Conclusion: The intensive
      treatment protocol is a successful method for improving picture naming even of
      untrained items.Further, the authors conclude that the intentional left-hand
      gesture contributed significantly to the generalization of treatment to
      discourse.

PMID- 24129015
TI  - The role of utterance length and position in 3-year-olds' production of third
      person singular -s.
AB  - PURPOSE Evidence from children's spontaneous speech suggests that utterance
      length and utterance position may help explain why children omit grammatical
      morphemes in some contexts but not others. This study investigated whether
      increased utterance length (hence, increased grammatical complexity) adversely
      affects children's third person singular -s production in more controlled
      experimental conditions. METHOD An elicited imitation task with 12 Australian
      English-speaking children ages 2;9 (years;months) to 3;2 (Mage = 2;11) was
      conducted comparing third person singular -s production in 3-word and 5-word
      utterances, both utterance medially (e.g., He sits back; He sits back and swings)
      and utterance finally (e.g., There he sits; That's the way he sits) using a
      within-subjects design. Children were shown pictorial representations of each
      utterance on a computer and were invited to repeat 16 pseudorandomized
      prerecorded utterances. Acoustic analysis determined the presence/absence and
      duration of the third person singular morpheme. RESULTS Third person singular
      production was significantly lower utterance medially compared to utterance
      finally for the 5-word utterances and significantly lower utterance medially in
      the 5-word compared to 3-word utterances. CONCLUSION These results suggest that
      increased utterance length results in significantly lower third person singular
      production, but only in the more articulatorily challenging utterance-medial
      position. Thus, morpheme omission is greatest at the intersection of grammatical
      and phonological complexity. 

PMID- 24129016
TI  - Modeling mechanisms of persisting and resolving delay in language development.
AB  - PURPOSE In this study, the authors used neural network modeling to investigate
      the possible mechanistic basis of developmental language delay and to test the
      viability of the hypothesis that persisting delay and resolving delay lie on a
      mechanistic continuum with normal development. METHOD The authors used a
      population modeling approach to study individual rates of development in 1,000
      simulated individuals acquiring a notional language domain (in this study,
      represented by English past tense). Variation was caused by differences in
      internal neurocomputational learning parameters as well as the richness of the
      language environment. An early language delay group was diagnosed, and individual
      trajectories were then traced. RESULTS Quantitative variations in learning
      mechanisms were sufficient to produce persisting delay and resolving delay
      subgroups in similar proportions to empirical observations. In the model,
      persisting language delay was caused by limitations in processing capacity,
      whereas resolving delay was caused by low plasticity. Richness of the language
      environment did not predict the emergence of persisting delay but did predict the
      final ability levels of individuals with resolving delay. CONCLUSION
      Mechanistically, it is viable that persisting delay and resolving delay are only
      quantitatively different. There may be an interaction between environmental
      factors and outcome groups, with individuals who have resolving delay being
      influenced more by the richness of the language environment. 

PMID- 24129017
TI  - A buoy for continuous monitoring of Suspended Sediment Dynamics.
AB  - Knowledge of Suspended Sediments Dynamics (SSD) across spatial scales is relevant
      for several fields of hydrology, such as eco-hydrological processes, the
      operation of hydrotechnical facilities and research on varved lake sediments as
      geoarchives. Understanding the connectivity of sediment flux between source areas
      in a catchment and sink areas in lakes or reservoirs is of primary importance to
      these fields. Lacustrine sediments may serve as a valuable expansion of
      instrumental hydrological records for flood frequencies and magnitudes, but
      depositional processes and detrital layer formation in lakes are not yet fully
      understood. This study presents a novel buoy system designed to continuously
      measure suspended sediment concentration and relevant boundary conditions at a
      high spatial and temporal resolution in surface water bodies. The buoy sensors
      continuously record turbidity as an indirect measure of suspended sediment
      concentrations, water temperature and electrical conductivity at up to nine
      different water depths. Acoustic Doppler current meters and profilers measure
      current velocities along a vertical profile from the water surface to the lake
      bottom. Meteorological sensors capture the atmospheric boundary conditions as
      main drivers of lake dynamics. It is the high spatial resolution of multi-point
      turbidity measurements, the dual-sensor velocity measurements and the temporally
      synchronous recording of all sensors along the water column that sets the system
      apart from existing buoy systems. Buoy data collected during a 4-month field
      campaign in Lake Mondsee demonstrate the potential and effectiveness of the
      system in monitoring suspended sediment dynamics. Observations were related to
      stratification and mixing processes in the lake and increased turbidity close to
      a catchment outlet during flood events. The rugged buoy design assures continuous
      operation in terms of stability, energy management and sensor logging throughout
      the study period. We conclude that the buoy is a suitable tool for continuous
      monitoring of suspended sediment concentrations and general dynamics in fresh
      water bodies. 

PMID- 24129018
TI  - A coded structured light system based on primary color stripe projection and
      monochrome imaging.
AB  - Coded Structured Light techniques represent one of the most attractive research
      areas within the field of optical metrology. The coding procedures are typically
      based on projecting either a single pattern or a temporal sequence of patterns to
      provide 3D surface data. In this context, multi-slit or stripe colored patterns
      may be used with the aim of reducing the number of projected images. However,
      color imaging sensors require the use of calibration procedures to address
      crosstalk effects between different channels and to reduce the chromatic
      aberrations. In this paper, a Coded Structured Light system has been developed by
      integrating a color stripe projector and a monochrome camera. A discrete coding
      method, which combines spatial and temporal information, is generated by
      sequentially projecting and acquiring a small set of fringe patterns. The method
      allows the concurrent measurement of geometrical and chromatic data by exploiting
      the benefits of using a monochrome camera. The proposed methodology has been
      validated by measuring nominal primitive geometries and free-form shapes. The
      experimental results have been compared with those obtained by using a time
      multiplexing gray code strategy. 

PMID- 24129019
TI  - Potential of visible and near infrared spectroscopy and pattern recognition for
      rapid quantification of notoginseng powder with adulterants.
AB  - Notoginseng is a classical traditional Chinese medical herb, which is of high
      economic and medical value. Notoginseng powder (NP) could be easily adulterated
      with Sophora flavescens powder (SFP) or corn flour (CF), because of their similar
      tastes and appearances and much lower cost for these adulterants. The objective
      of this study is to quantify the NP content in adulterated NP by using a rapid
      and non-destructive visible and near infrared (Vis-NIR) spectroscopy method.
      Three wavelength ranges of visible spectra, short-wave near infrared spectra
      (SNIR) and long-wave near infrared spectra (LNIR) were separately used to
      establish the model based on two calibration methods of partial least square
      regression (PLSR) and least-squares support vector machines (LS-SVM),
      respectively. Competitive adaptive reweighted sampling (CARS) was conducted to
      identify the most important wavelengths/variables that had the greatest influence
      on the adulterant quantification throughout the whole wavelength range. The CARS
      PLSR models based on LNIR were determined as the best models for the
      quantification of NP adulterated with SFP, CF, and their mixtures, in which the
      rP values were 0.940, 0.939, and 0.867 for the three models respectively. The
      research demonstrated the potential of the Vis-NIR spectroscopy technique for the
      rapid and non-destructive quantification of NP containing adulterants. 

PMID- 24129020
TI  - G3 assisted rational design of chemical sensor array using carbonitrile neutral
      receptors.
AB  - Combined computational and experimental strategies for the systematic design of
      chemical sensor arrays using carbonitrile neutral receptors are presented.
      Binding energies of acetonitrile, n-pentylcarbonitrile and malononitrile with
      Ca(II), Mg(II), Be(II) and H+ have been investigated with the B3LYP, G3, CBS-QB3,
      G4 and MQZVP methods, showing a general trend H+ > Be(II) > Mg(II) > Ca(II).
      Hydrogen bonding, donor-acceptor and cation-lone pair electron simple models were
      employed in evaluating the performance of computational methods. Mg(II) is bound
      to acetonitrile in water by 12.5 kcal/mol, and in the gas phase the receptor is
      more strongly bound by 33.3 kcal/mol to Mg(II) compared to Ca(II). Interaction of
      bound cations with carbonitrile reduces the energies of the MOs involved in the
      proposed sigma-p conjugated network. The planar malononitrile-Be(II) complex
      possibly involves a pi-network with a cationic methylene carbon. Fabricated
      potentiometric chemical sensors show distinct signal patterns that can be
      exploited in sensor array applications.

PMID- 24129021
TI  - Development of a real time sparse non-negative matrix factorization module for
      cochlear implants by using xPC target.
AB  - Cochlear implants (CIs) require efficient speech processing to maximize
      information transmission to the brain, especially in noise. A novel CI processing
      strategy was proposed in our previous studies, in which sparsity-constrained non
      negative matrix factorization (NMF) was applied to the envelope matrix in order
      to improve the CI performance in noisy environments. It showed that the algorithm
      needs to be adaptive, rather than fixed, in order to adjust to acoustical
      conditions and individual characteristics. Here, we explore the benefit of a
      system that allows the user to adjust the signal processing in real time
      according to their individual listening needs and their individual hearing
      capabilities. In this system, which is based on MATLAB(r), SIMULINK(r) and the
      xPC TargetTM environment, the input/outupt (I/O) boards are interfaced between
      the SIMULINK blocks and the CI stimulation system, such that the output can be
      controlled successfully in the manner of a hardware-in-the-loop (HIL) simulation,
      hence offering a convenient way to implement a real time signal processing module
      that does not require any low level language. The sparsity constrained parameter
      of the algorithm was adapted online subjectively during an experiment with normal
      hearing subjects and noise vocoded speech simulation. Results show that subjects
      chose different parameter values according to their own intelligibility
      preferences, indicating that adaptive real time algorithms are beneficial to
      fully explore subjective preferences. We conclude that the adaptive real time
      systems are beneficial for the experimental design, and such systems allow one to
      conduct psychophysical experiments with high ecological validity.

PMID- 24129022
TI  - A fast smoothing algorithm for post-processing of surface reflectance spectra
      retrieved from airborne imaging spectrometer data.
AB  - Surface reflectance spectra retrieved from remotely sensed hyperspectral imaging
      data using radiative transfer models often contain residual atmospheric
      absorption and scattering effects. The reflectance spectra may also contain minor
      artifacts due to errors in radiometric and spectral calibrations. We have
      developed a fast smoothing technique for post-processing of retrieved surface
      reflectance spectra. In the present spectral smoothing technique, model-derived
      reflectance spectra are first fit using moving filters derived with a cubic
      spline smoothing algorithm. A common gain curve, which contains minor artifacts
      in the model-derived reflectance spectra, is then derived. This gain curve is
      finally applied to all of the reflectance spectra in a scene to obtain the
      spectrally smoothed surface reflectance spectra. Results from analysis of
      hyperspectral imaging data collected with the Airborne Visible/Infrared Imaging
      Spectrometer (AVIRIS) data are given. Comparisons between the smoothed spectra
      and those derived with the empirical line method are also presented. 

PMID- 24129023
TI  - Multi-channel hyperspectral fluorescence detection excited by coupled plasmon
      waveguide resonance.
AB  - We propose in this paper a biosensor scheme based on coupled plasmon-waveguide
      resonance (CPWR) excited fluorescence spectroscopy. A symmetrical structure that
      offers higher surface electric field strengths, longer surface propagation
      lengths and depths is developed to support guided waveguide modes for the
      efficient excitation of fluorescence. The optimal parameters for the sensor films
      are theoretically and experimentally investigated, leading to a detection limit
      of 0.1 nM (for a Cy5 solution). Multiplex analysis possible with the fluorescence
      detection is further advanced by employing the hyperspectral fluorescence
      technique to record the full spectra for every pixel on the sample plane. We
      demonstrate experimentally that highly overlapping fluorescence (Cy5 and
      Dylight680) can be distinguished and ratios of different emission sources can be
      determined accurately. This biosensor shows great potential for multiplex
      detections of fluorescence analytes. 

PMID- 24129024
TI  - Omnidirectional structured light in a flexible configuration.
AB  - Structured light is a perception method that allows us to obtain 3D information
      from images of the scene by projecting synthetic features with a light emitter.
      Traditionally, this method considers a rigid configuration, where the position
      and orientation of the light emitter with respect to the camera are known and
      calibrated beforehand. In this paper we propose a new omnidirectional structured
      light system in flexible configuration, which overcomes the rigidness of the
      traditional structured light systems. We propose the use of an omnidirectional
      camera combined with a conic pattern light emitter. Since the light emitter is
      visible in the omnidirectional image, the computation of its location is
      possible. With this information and the projected conic in the omnidirectional
      image, we are able to compute the conic reconstruction, i.e., the 3D information
      of the conic in the space. This reconstruction considers the recovery of the
      depth and orientation of the scene surface where the conic pattern is projected.
      One application of our proposed structured light system in flexible configuration
      consists of a wearable omnicamera with a low-cost laser in hand for visual
      impaired personal assistance. 

PMID- 24129025
TI  - A novel B/C inter-genotype recombinant of hepatitis B virus identified in north
      west China.
AB  - The characteristics of life-long persistent infection of hepatitis B virus (HBV)
      and the prevalence of different genotypes of HBV in China may cause new
      recombinants. In north-west China, HBV inter-genotype recombinants have been
      reported frequently over the last decade. Here, we report a B/C inter-genotype
      recombinant HBV with a novel genome mosaic structure from Lanzhou, a city in
      north-west China. 

PMID- 24129026
TI  - The host-range tdCE phenotype of Chandipura virus is determined by mutations in
      the polymerase gene.
AB  - The emerging arbovirus Chandipura virus (CV) has been implicated in epidemics of
      acute encephalitis in India with high mortality rates. The isolation of
      temperature-dependent host-range (tdCE) mutants, which are impaired in growth at
      39  degrees C in chick embryo (CE) cells but not in monkey cells, highlights a
      dependence on undetermined host factors. We have characterized three tdCE
      mutants, each containing one or more coding mutations in the RNA polymerase gene
      and two containing additional mutations in the attachment protein gene. Using
      reverse genetics, we showed that a single amino acid change in the virus
      polymerase of each mutant was responsible for the host-range specificity. In CE
      cells at the non-permissive temperature, the discrete cytoplasmic replication
      complexes seen in mammalian cells or at the permissive temperature in CE cells
      were absent with the tdCE mutants, consistent with the tdCE lesions causing
      disruption of the replication complexes in a host-dependent manner. 

PMID- 24129027
TI  - Development and validation of a nutritional questionnaire for the Palestine
      population.
AB  - OBJECTIVE: Dietary habits vary widely among regions and cultural groups, and FFQ
      need to be designed for specific populations. The objectives of the present study
      were to develop and test the repeatability and relative validity of a medium
      length semi-quantitative FFQ for measuring the energy and macronutrient intakes
      of a specific population and to contribute a methodological framework for this
      procedure. SETTING: Palestinian families in the Hebron area. DESIGN: After a
      preliminary survey of a subgroup of homemakers using 3 d diet recall, stepwise
      multiple regression analysis was used for selected nutrients to choose foods for
      inclusion in the FFQ. SUBJECTS: The FFQ was administered to a study population of
      169 women representing the same number of families. RESULTS: The Wilcoxon test
      and Bland-Altman plots were used to compare the FFQ results with the mean 3 d
      diet recall results. A high level of concordance was found, validating the FFQ.
      In this population, the mean consumption of SFA was above recommendations and the
      intakes of vitamin D, folic acid, Ca, Fe and K were deficient. CONCLUSIONS: The
      availability of diet assessment instruments designed for specific populations and
      cultures is of immense value to researchers and policy makers. The study
      describes a simple and effective method to develop and validate an FFQ for a
      given population of interest.

PMID- 24129028
TI  - Barbados green monkeys (Chlorocebus sabaeus) recognize ancestral alarm calls
      after 350 years of isolation.
AB  - Vervet monkeys (Chlorocebus pygerythrus) produce alarm calls and anti-predator
      behaviors that are specific to a threatening predator's mode of attack. Upon
      hearing a leopard alarm, the monkeys will run up trees where they are relatively
      safe. In contrast, eagle alarms prompt the monkeys to run under bushes and snake
      alarms stimulate bipedal standing. Early researchers proposed that the meaning of
      each alarm call is conveyed by observational learning. If this true then absence
      of the predator that elicits the alarm call may lead to alteration or decay of
      the alarm's meaning since there is no longer opportunity for observational
      learning to occur. The present study tested this hypothesis by presenting alarm
      calls to a closely related species of monkeys (Chlorocebus sabaeus) that have
      been isolated from their ancestral predators for more than 350 years. The monkeys
      ran up trees in response to a leopard alarm, but not when the same alarm was
      played backwards and not in response to a snake alarm. Snake alarms failed to
      reliably elicit bipedal standing. These results suggest that the leopard alarm
      call conveys the same information to Barbados green monkeys as West African green
      monkeys despite generations of isolation from leopards. 

PMID- 24129029
TI  - Beginnings of a synthetic approach to desert ant navigation.
AB  - In a synthetic approach to studying navigational abilities in desert ants, we
      review recent work comparing ants living in different visual ecologies. Those
      living in a visually rich habitat strewn with tussocks, bushes, and trees are
      compared to those living in visually barren salt pans, as exemplified by the
      Central Australian Melophorus bagoti and the North African Cataglyphis fortis,
      respectively. In bare habitats the navigator must rely primarily on path
      integration, keeping track of the distance and direction in which it has
      travelled, while in visually rich habitats the navigator can rely more on
      guidance by the visual panorama. Consistent with these expectations, C. fortis
      performs better than M. bagoti on various measures of precision at path
      integration. In contrast, M. bagoti learned a visually based associative task
      better than C. fortis, the latter generally failing at the task. Both these ants,
      however, exhibit a similar pattern of systematic search as a 'back up' strategy
      when other navigational strategies fail. A newly investigated salt-pan species of
      Melophorus (as yet unnamed) resembles C. fortis more, and its congener M. bagoti
      less, in its path integration. The synthetic approach would benefit from
      comparing more species chosen to address evolutionary questions. This article is
      part of a Special Issue entitled: CO3 2013. 

PMID- 24129030
TI  - Genomic medicine in primary care: barriers and assets.

PMID- 24129031
TI  - Interprofessional education in team communication: working together to improve
      patient safety.
AB  - BACKGROUND: Communication failures in healthcare teams are associated with
      medical errors and negative health outcomes. These findings have increased
      emphasis on training future health professionals to work effectively within
      teams. The Team Strategies and Tools to Enhance Performance and Patient Safety
      (TeamSTEPPS) communication training model, widely employed to train healthcare
      teams, has been less commonly used to train student interprofessional teams. The
      present study reports the effectiveness of a simulation-based interprofessional
      TeamSTEPPS training in impacting student attitudes, knowledge and skills around
      interprofessional communication. METHODS: Three hundred and six fourth-year
      medical, third-year nursing, second-year pharmacy and second-year physician
      assistant students took part in a 4 h training that included a 1 h TeamSTEPPS
      didactic session and three 1 h team simulation and feedback sessions. Students
      worked in groups balanced by a professional programme in a self-selected focal
      area (adult acute, paediatric, obstetrics). Preassessments and postassessments
      were used for examining attitudes, beliefs and reported opportunities to observe
      or participate in team communication behaviours. RESULTS: One hundred and forty
      nine students (48.7%) completed the preassessments and postassessments.
      Significant differences were found for attitudes toward team communication
      (p<0.001), motivation (p<0.001), utility of training (p<0.001) and self-efficacy
      (p=0.005). Significant attitudinal shifts for TeamSTEPPS skills included, team
      structure (p=0.002), situation monitoring (p<0.001), mutual support (p=0.003) and
      communication (p=0.002). Significant shifts were reported for knowledge of
      TeamSTEPPS (p<0.001), advocating for patients (p<0.001) and communicating in
      interprofessional teams (p<0.001). CONCLUSIONS: Effective team communication is
      important in patient safety. We demonstrate positive attitudinal and knowledge
      effects in a large-scale interprofessional TeamSTEPPS-based training involving
      four student professions.

PMID- 24129032
TI  - Novel cancer therapies: treatments driven by tumour biology.
AB  - The traditional view is that treatments within oncology largely consist of
      chemotherapy, which aims to maximise damage to the rapidly dividing cancer cells
      but often at the expense of normal cells and overall quality of life for the
      patient. The development of anticancer drugs has changed from the serendipitous
      discoveries of the past, to today's purposeful targeting of cancer cells which
      takes advantage of novel technological developments and a greater understanding
      of tumour biology. The aim of these new treatments is to affect the essential
      function of the cancer cell while sparing normal cells, and limiting side
      effects. The phenotypic characteristics of tumours, such as unregulated growth
      signalling, development of new vascular systems and the evasion of immune
      destruction are used to identify potential drug targets. Here we review the
      clinical evidence and molecular mechanisms for novel therapies that are currently
      in use and those that are in development. 

PMID- 24129033
TI  - Whipple's disease.
AB  - Whipple's disease is a chronic, systemic infection caused by Tropheryma whipplei.
      Gene amplification, isolation and DNA sequencing of T whipplei have extended our
      knowledge of this pathogen, which is now recognised as a ubiquitous commensal
      bacterium. The spectrum of signs associated with T whipplei has now been extended
      beyond the classic form, which affects middle-aged men, and begins with recurrent
      arthritis followed several years later by digestive problems associated with
      other diverse clinical signs. Children may present an acute primary infection,
      but only a small number of people with a genetic predisposition subsequently
      develop authentic Whipple's disease. This bacterium may also cause localised
      chronic infections with no intestinal symptoms: endocarditis, central nervous
      system involvement, arthritis, uveitis and spondylodiscitis. An impaired TH1
      immune response is seen. T whipplei replication in vitro is dependent on
      interleukin 16 and is accompanied by the apoptosis of host cells, facilitating
      dissemination of the bacterium. In patients with arthritis, PCR with samples of
      joint fluid, saliva and stools has become the preferred examination for
      diagnosis. Immunohistochemical staining is also widely used for diagnosis.
      Treatment is based on recent microbiological data, but an immune reconstitution
      syndrome and recurrence remain possible. The future development of serological
      tests for diagnosis and the generalisation of antigen detection by
      immunohistochemistry should make it possible to obtain a diagnosis earlier and
      thus to decrease the morbidity, and perhaps also the mortality, associated with
      this curable disease which may, nonetheless, be fatal if diagnosed late or in an
      extensive systemic form. 

PMID- 24129034
TI  - Stem cells, angiogenesis and muscle healing: a potential role in massage
      therapies?
AB  - Skeletal muscle injuries are among the most common and frequently disabling
      injuries sustained by athletes. Repair of injured skeletal muscle is an area that
      continues to present a challenge for sports medicine clinicians and researchers
      due, in part, to complete muscle recovery being compromised by development of
      fibrosis leading to loss of function and susceptibility to re-injury. Injured
      skeletal muscle goes through a series of coordinated and interrelated phases of
      healing including degeneration, inflammation, regeneration and fibrosis. Muscle
      regeneration initiated shortly after injury can be limited by fibrosis which
      affects the degree of recovery and predisposes the muscle to reinjury. It has
      been demonstrated in animal studies that antifibrotic agents that inactivate
      transforming growth factor (TGF)-beta1 have been effective at decreasing scar
      tissue formation. Several studies have also shown that vascular endothelial
      growth factor (VEGF) can increase the efficiency of skeletal muscle repair by
      increasing angiogenesis and, at the same time, reducing the accumulation of
      fibrosis. We have isolated and thoroughly characterised a population of skeletal
      muscle-derived stem cells (MDSCs) that enhance repair of damaged skeletal muscle
      fibres by directly differentiating into myofibres and secreting paracrine factors
      that promote tissue repair. Indeed, we have found that MDSCs transplanted into
      skeletal and cardiac muscles have been successful at repair probably because of
      their ability to secrete VEGF that works in a paracrine fashion. The application
      of these techniques to the study of sport-related muscle injuries awaits
      investigation. Other useful strategies to enhance skeletal muscle repair through
      increased vascularisation may include gene therapy, exercise, neuromuscular
      electrical stimulation and, potentially, massage therapy. Based on recent studies
      showing an accelerated recovery of muscle function from intense eccentric
      exercise through massage-based therapies, we believe that this treatment modality
      offers a practical and non-invasive form of therapy for skeletal muscle injuries.
      However, the biological mechanism(s) behind the beneficial effect of massage are
      still unclear and require further investigation using animal models and
      potentially randomised, human clinical studies. 

PMID- 24129035
TI  - The age of Twitter.

PMID- 24129036
TI  - New insights into an autoimmune mechanism, pharmacological treatment and
      relationship between multiple sclerosis and inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) and multiple sclerosis (MS) are autoimmune
      diseases with a close relationship to their disease pattern and immunologic
      cascade with considerable morbidity and mortality. This article provides insight
      of why tumor necrosis factor blockers couldn't work in multiple sclerosis and why
      interferon-beta doesn't work in inflammatory bowel disease. In this article, we
      provide a detailed review of the linkage and potential interchangeable medication
      between IBD and MS in addition to Natalizumab, Trichuris suis egg therapy and
      vitamin D. Different treatment strategies may have potential in treating both
      diseases in the future. 

PMID- 24129037
TI  - Prospective study to evaluate the association between systemic sclerosis and
      occupational exposure and review of the literature.
AB  - INTRODUCTION: Systemic sclerosis (SSc) has complex pathogenesis and likely
      multifactorial causes. Environmental exposures have been suggested to play a role
      in SSc pathogenesis, including occupational exposure to pollutants and chemicals
      as well as use of drugs leading to modulation of immune response. Thus, this case
      control study aimed to assess: the relationship between SSc and occupational
      exposure; and the risk of SSc related to occupational exposure in male and female
      patients. METHODS: From 2005 to 2008, 100 patients with a definite diagnosis of
      SSc were included in the study; 3 age, gender, and smoking habits matched
      controls were selected for each patient. A committee of experts evaluated blindly
      occupational exposure to crystalline silica, white spirit, organic solvents,
      ketones, welding fumes, epoxy resins, and pesticides; an occupational exposure
      score was calculated for all subjects. Our findings were compared with previous
      data in the literature. RESULTS: Increased ORs for SSc were found for:
      crystalline silica (p<0.0001), white spirit (p<0.0001), aromatic solvents
      (p=0.0002), chlorinated solvents (p=0.014), trichlorethylene (p=0.044), ketones
      (p=0.002) and welding fumes (p=0.021). Elevated risk associated with high final
      cumulative score in SSc was observed for: crystalline silica, white spirit,
      chlorinated solvents, trichlorethylene, aromatic solvents, any type of solvents,
      ketones and welding fumes. A marked association between SSc and occupational
      exposure was further found for: 1) crystalline silica, chlorinated solvents,
      trichloroethylene, white spirit, ketones and welding fumes in male patients; and
      2) white spirit, aromatic solvents, any type of solvent and ketones in female
      patients. Finally, we did not find an association between SSc and: 1) the use of
      drugs that have been speculated to play a role in SSc onset (anorexigens,
      pentazocine, bromocriptine, l-tryptophan); 2) implants - that are prosthesis,
      silicone implants, and contact lenses; and 3) dyeing hair. In the literature, SSc
      has been associated with occupational exposure to silica and solvents, while the
      association between SSc and specific organic solvents and welding fumes has been
      anecdotally reported. CONCLUSION: The following occupational factors have an
      impact in the development of SSc: crystalline silica, white spirit, aromatic
      solvents, chlorinated solvents, trichlorethylene, ketones and welding fumes. The
      risk of SSc appears to be markedly associated with high cumulative exposure.
      Finally, the association between SSc and occupational exposure may be variable
      according to gender.

PMID- 24129038
TI  - Corrigendum.

PMID- 24129039
TI  - Three-dimensional rodent motion analysis and neurodegenerative disorders.
AB  - BACKGROUND: Three-dimensional (3D) motion analysis is established in
      investigating, human pathological motion. In the field of gait, its use results
      in the objective identification of primary, and secondary causes of deviations,
      many current interventions are the result of pre- and post-testing, and it was
      shown recently that it can result in decreased number of surgeries and overall
      cost of care. Consequently, recent attempts have implemented 3D motion analysis
      using rat models to study, parkinsonism. However, to-date, a 3D user friendly
      analytical approach using rodent models to, identify etiologies of age-related
      motor impairment and accompanying pathologies has not been, implemented. NEW
      METHOD: We have developed and presented all aspects of a 3D, three body-segment
      rodent model, to analyze motions of the lower, upper and head segments between
      rodents of parkinsonism-type and, normal aging during free walking. Our model
      does not require transformation matrices to describe the, position of each body
      segment. Because body-segment positions are not considered to consist of three,
      rotations about the laboratory axes, the rotations are not sequence dependent.
      RESULTS: Each body-segment demonstrated distinct 3D movement patterns. The
      parkinsonism-type, genotype walked slower with less range of motion, similarly to
      patients with parkinsonism. COMPARISON WITH EXISTING METHODS: This is the first
      model considering the rodent's body as three, distinct segments. To the best of
      our knowledge, it is the first model to ever consider and report the 3D, head
      motion patterns. CONCLUSIONS: This novel approach will allow unbiased analysis of
      spontaneous locomotion in mouse, models of parkinsonism or normal aging.

PMID- 24129040
TI  - Ontogenetic changes in limb bone structural proportions in mountain gorillas
      (Gorilla beringei beringei).
AB  - Behavioral studies indicate that adult mountain gorillas (Gorilla beringei) are
      the most terrestrial of all nonhuman hominoids, but that infant mountain gorillas
      are much more arboreal. Here we examine ontogenetic changes in diaphyseal
      strength and length of the femur, tibia, humerus, radius, and ulna in 30 Virunga
      mountain gorillas, including 18 immature specimens and 12 adults. Comparisons are
      also made with 14 adult western lowland gorillas (Gorilla gorilla gorilla), which
      are known to be more arboreal than adult mountain gorillas. Infant mountain
      gorillas have significantly stronger forelimbs relative to hind limbs than older
      juveniles and adults, but are nonsignificantly different from western lowland
      gorilla adults. The change in inter-limb strength proportions is abrupt at about
      two years of age, corresponding to the documented transition to committed
      terrestrial quadrupedalism in mountain gorillas. The one exception is the ulna,
      which shows a gradual increase in strength relative to the radius and other long
      bones during development, possibly corresponding to the gradual adoption of
      stereotypical fully pronated knuckle-walking in older juvenile gorillas. Inter
      limb bone length proportions show a contrasting developmental pattern, with hind
      limb/forelimb length declining rapidly from birth to five months of age, and then
      showing no consistent change through adulthood. The very early change in length
      proportions, prior to significant independent locomotion, may be related to the
      need for relatively long forelimbs for climbing in a large-bodied hominoid.
      Virunga mountain gorilla older juveniles and adults have equal or longer forelimb
      relative to hind limb bones than western lowland adults. These findings indicate
      that both ontogenetically and among closely related species of Gorilla, long bone
      strength proportions better reflect actual locomotor behavior than bone length
      proportions. 

PMID- 24129041
TI  - Memory deficits in late-onset schizophrenia.
AB  - Late-onset schizophrenia (LOS) is a controversial diagnosis, mainly characterized
      by more positive symptoms and less deterioration. LOS could be considered as
      either an extreme of typical schizophrenia (but for old age patients, and short
      duration of the disorder), or an independent group of patients with a specific
      diagnosis, with no clear evidence in favor or against any of these hypotheses.
      The aim of the present study is to characterize the memory cognitive profile of
      LOS patients without related organic factors (N=25), compared to early-onset
      schizophrenic patients (EOS, N=44), matched for the duration of the disorder, and
      healthy controls (HC, N=23), matched for the age of patients. Lifetime clinical
      symptoms and functioning were collected using the DIGS and the PANSS, and
      components of memory capacity were assessed with the Forward and Backward Digit
      Span Tasks, Rey Complex Figure and Verbal Fluency Tests. LOS patients were
      performing significantly better than EOS patients on the digit span task, Rey's
      complex figure at T1 score and phonemic verbal fluency. However, LOS had
      significantly lower performances than healthy controls on the digit span task and
      on both verbal fluency tests. This study provides evidence that LOS had
      intermediate outcome compared to EOS and controls. LOS can therefore be in line
      with a dimensional clinical approach of schizophrenia, whereby it presents few
      memory deficits and few disorganization and negative symptoms with mostly
      positive symptoms and possibly etiopathogenic specificities. Further studies
      including more specific memory assessment tests and larger samples are needed to
      confirm the present finding. 

PMID- 24129042
TI  - Relationship between atopy, allergic diseases and total serum IgE levels among
      HIV-infected children.
AB  - In recent years there has been increasing prevalence of allergic diseases
      globally, especially in children. Many IgE-dependent allergic manifestations have
      been described in HIV-infected individuals. However, it seems to be controversial
      whether immunological changes, such as IgE elevation, results from the infection
      or is related to the presence of allergy in these subjects. The aim of this study
      was to survey the literature of articles focused on the pediatric population with
      HIV infection, total serum IgE and / or allergic diseases and atopy. We conducted
      a narrative review, from articles found in Medline and LILACS published in the
      last 20 years using the key words: children, allergic disease, HIV, IgE.    
      After eliminating duplicates in databases, 33 international articles were
      considered. We selected seven articles that addressed the proposed aim of study
      to perform a complete reading and discussing. CONCLUSION: this review showed that
      high IgE levels can be found for other reasons than atopy or allergic disease in
      children with HIV. Specific IgE against the antigens of the HIV virus and higher
      levels of total serum IgE can be seen in children with or without aggravation of
      AIDS. Finally, we reiterate the call made by the authors of some studies for more
      studies on the subject, especially with larger samples in pediatric population.

PMID- 24129043
TI  - Heterogenity of IgE response to walnut and hazelnut in Italian allergic patients.
AB  - BACKGROUND: The prevalence of IgE reactivity against genuine walnut and hazelnut
      allergens is poorly defined. OBJECTIVE: The IgE response to walnut and hazelnut
      was investigated in Italian patients with primary allergy to these nuts. METHODS:
      Sera from 36 patients allergic to hazelnut and/or walnut, not reactive to PR-10,
      profilin, and LTP, underwent immunoblot analysis with extracts of both nuts.
      RESULTS: Most patients had a history of systemic symptoms following the ingestion
      of the offending food(s). Twelve patients were sensitized to both walnut and
      hazelnut, and 13 were sensitized to other nuts and seeds (cashew, peanut, sesame,
      pine nut, almond, Brazil nut, and pistachio). On walnut immunoblot, the 7 sera
      which scored positive showed much variability in their IgE profile. Two reacted
      uniquely at 10 kDa, and the others at 35 , 40, 45, 50, 67, and > 67 kDa. The
      profiles obtained under reducing and non-reducing conditions showed several
      differences. The 7 sera positive on hazelnut immunoblot under reducing conditions
      recognized sera at 10 kDa and at <10 kDa (n=1), 20 kDa (n=4), at about 22, 24,
      30, 40, 43, 58, 60, and 90 kDa, and higher m.w. in other cases. Under non
      reducing conditions IgE reactivity at 20, 28, 35, 40, 45, 60, 90, and 100 kDa,
      was detected. Only two sera scored positive under both conditions and showed an
      IgE profile that partly changed from one assay to another. CONCLUSION: The
      current list of walnut and hazelnut allergens is far from being complete. Both
      reducing and non-reducing conditions are needed to detect IgE reactivity in
      individual patients.

PMID- 24129044
TI  - Improvement of quality of life in allergic rhinoconjunctivitis patients using
      nasal filters, a preliminary study.
AB  - BACKGROUND: Allergic rhinoconjunctivitis is a clinical condition that impairs
      quality of life. The use of traditional drugs in many cases is not enough to
      improve quality of life in these patients. METHODS: In this pilot study we used
      the Sanispira Nasal filters in 15 patients (mean age 34,7 years) affected by
      allergic rhinoconjunctivitis for 18 days. At each follow-up visit, patients were
      assessed with a specific quality of life questionnaire, a symptoms form and a
      drugs form that evaluates the use of antiallergic drugs in the last week.
      Patients sensitive to environmental allergens wore Sanispira nasal filters during
      the day, while patients sensitive to domestic allergens wore the device during
      the night. RESULTS: Thirteen patients completed the study. We found an
      improvement significative (p=0,0241) of the total score of RQLQ of 23,10 points
      between baseline and 18 days ( total score at baseline prior to nasal filter
      insertion= 60,60, at 1 week = 42, 28, at 18 days= 34, 10). A significative
      improvement in the nasal symptoms domain between baseline and 18 days (in
      particular stuffy nose p=0,047; runny nose p=0,012; sneezing p=0,0021; ) and one
      item of practical problems domain, the need to repeatedly blow the nose(p=0,082).
      The total score of symptoms evaluated with the symptoms form improved
      significantly from baseline to 18 days. Total symptoms score at baseline was 9,7;
      at 1 week it was 8,1 and at 18 days it was 4,7. The improvement was statistically
      significant (p=0,0092). Three of the thirteen patients that completed the study
      eliminated completely the use of drugs during of the study. CONCLUSIONS: The use
      of SANISPIRA (r), has shown encouraging results, with an improvement in the
      quality of life in Rhinoconjunctivitis patients specially an improvement in nasal
      and ocular symptoms.

PMID- 24129045
TI  - Desensitization of darbepoetin-alpha: a case report.
AB  - Human recombinant erythropoietins (EPO) and darbepoetins are widely used for
      anemias associated with chronic kidney disease.  Allergic reactions to
      erythropoetins and darbepoetins have only occasionally been reported. These skin
      reactions include pruritus, wheals at the injection site, orofacial anaphylaxis
      and anjioedema. In this article, we report an 11 year-old female who experienced
      generalized   erithematous skin eruption and desquamation after both
      erythropoietin and darbepoetin treatments.  We successfully used darbepoetin with
      the support of premedication and desensitization. 

PMID- 24129046
TI  - A case of acute generalized exanthematous pustulosis due to amoxicillin
      clavulanate with multiple positivity to beta-lactam patch testing.
AB  - We present a case of acute generalized exanthematous pustolosis (AGEP) induced by
      amoxicillin-clavulanate. Clinical diagnosis was confirmed by symptoms
      presentation and  histological features (Euroscar score point compatible with
      definite diagnosis). Patch testing performer six months later confirmed
      sensitization to the culprit drug and showed positivity also to other beta-lactam
      antibiotics (penicillin G and cephalexin). We believe that a T cell delayed
      response to betalactams common ring could be involved. 

PMID- 24129047
TI  - Interferon beta 1a anaphylaxis, a case report. Standardization of non-irritating
      concentration for allergy skin tests.
AB  - Multiple sclerosis is a disease with a potentially severe prognosis and
      epidemiologically increasing. Interferon beta 1a is a very useful maintenance
      therapy widely used by neurologists. In the literature, there are several case
      reports of  hypersensitivity reactions. In this case report we describe an
      anaphylactic IgE mediated reaction to interferon beta 1a. We also describe, for
      the first time in the medical literature, the non-irritating concentration (NIC)
      to be used for skin tests. 

PMID- 24129048
TI  - Novel mathematical algorithm for pupillometric data analysis.
AB  - Pupillometry is used clinically to evaluate retinal and optic nerve function by
      measuring pupillary response to light stimuli. We have developed a mathematical
      algorithm to automate and expedite the analysis of non-filtered, non-calculated
      pupillometric data obtained from mouse pupillary light reflex recordings,
      obtained from dynamic pupillary diameter recordings following exposure of varying
      light intensities. The non-filtered, non-calculated pupillometric data is
      filtered through a low pass finite impulse response (FIR) filter. Thresholding is
      used to remove data caused by eye blinking, loss of pupil tracking, and/or head
      movement. Twelve physiologically relevant parameters were extracted from the
      collected data: (1) baseline diameter, (2) minimum diameter, (3) response
      amplitude, (4) re-dilation amplitude, (5) percent of baseline diameter, (6)
      response time, (7) re-dilation time, (8) average constriction velocity, (9)
      average re-dilation velocity, (10) maximum constriction velocity, (11) maximum re
      dilation velocity, and (12) onset latency. No significant differences were noted
      between parameters derived from algorithm calculated values and manually derived
      results (p >= 0.05). This mathematical algorithm will expedite endpoint data
      derivation and eliminate human error in the manual calculation of pupillometric
      parameters from non-filtered, non-calculated pupillometric values. Subsequently,
      these values can be used as reference metrics for characterizing the natural
      history of retinal disease. Furthermore, it will be instrumental in the
      assessment of functional visual recovery in humans and pre-clinical models of
      retinal degeneration and optic nerve disease following pharmacological or gene
      based therapies.

PMID- 24129049
TI  - Significant neurologic recovery after traumatic cervical spondyloptosis and
      spinal cord injury.

PMID- 24129050
TI  - Comparison of minimal access and traditional anterior spinal surgery in managing
      infectious spondylitis: a minimum 2-year follow-up.
AB  - BACKGROUND CONTEXT: Traditional anterior spinal surgery (TASS) for the
      thoracolumbar spine is associated with significant morbidities. To avoid
      excessive tissue damage, minimal access spinal surgery (MASS) has been developed
      to treat a variety of anterior spinal disorders at the authors' institution. No
      previous reports comparing the outcomes of MASS and TASS for the treatment of
      infectious spondylitis were noted in the literature, to our knowledge. PURPOSE:
      The aim of this study was to investigate the outcomes of MASS in managing
      infectious spondylitis and compare the results to TASS with a minimum follow-up
      of 2 years. STUDY DESIGN: A retrospective comparative cohort study in a single
      center. PATIENT SAMPLE: Forty patients with thoracic or lumbar infectious
      spondylitis who underwent anterior spinal surgery were enrolled. OUTCOME
      MEASURES: Perioperative data including operative time, estimated blood loss,
      packed red blood cell transfusion, postoperative tube drainage, need for
      intensive care, and length of hospital stay. Postoperative complications were
      classified according to the Clavien-Dindo system. Fusion grade was assessed by
      plain radiographs on the basis of Burkus criteria. METHODS: Between January 2002
      and June 2010, all enrolled patients were collected via the Spine Operation
      Registry of the authors' institution. There were 23 MASS patients and 17 TASS
      patients. The average follow-up was 4.2 years (range, 2-9 years). RESULTS: The
      mean estimated blood loss in MASS and TASS groups was 521.7 versus 979.4 mL
      (p=.007), intraoperative transfusion of packed red blood cells was 0.9 versus 2.7
      units (p=.019), the amount of postoperative tube drainage was 235.2 versus 454.3
      mL (p=.005), the number of patients requiring postoperative intensive care was 2
      versus 7 (p=.023), and length of hospital stay was 15.4 versus 22.9, respectively
      (p=.043). The overall complication rate in the MASS group was 17% and 59% in the
      TASS group (p=.007). No major complications occurred in the MASS group, whereas
      four occurred in the TASS group (p=.026). Bone graft union was achieved in 38 of
      39 survival patients (97%), with no difference between the groups. One patient in
      TASS had a pseudarthrosis and needed a posterior instrumented fusion.
      CONCLUSIONS: Minimal access spinal surgery has been suggested to be an effective
      and safe technique in treating thoracic and lumbar infectious spondylitis.
      Minimal access spinal surgery did not need endoscopic equipments or complex
      surgical instruments. Furthermore, in comparison to TASS, MASS resulted in a
      reduced blood transfusion amount, decreased intensive care unit stay, reduced
      overall length of stay, and reduced surgical complication rate. Nevertheless, the
      risks may be increased in performing MASS on patients with multilevel
      involvement, which could be associated with high vascularity, alternated vascular
      anatomy, increased soft-tissue edema, and adhesion.

PMID- 24129051
TI  - Estrogenic effect of the phytoestrogen biochanin A in zebrafish, Danio rerio, and
      brown trout, Salmo trutta.
AB  - Isoflavones with estrogenic activity produced in Fabaceae plants are known to
      leach from agricultural areas to freshwater systems, but the effect of waterborne
      isoflavones in fish has not been thoroughly characterized. Therefore, the
      estrogenic effect of waterborne biochanin A was investigated in zebrafish (Danio
      rerio) and juvenile brown trout (Salmo trutta). Exposure of juvenile brown trout
      to 10 MUg biochanin AL(-1) or higher caused marked vitellogenin induction after 9
      10 days of exposure and so did exposure to 186 MUg biochanin AL(-1) for 6h.
      Following 8d of exposure, a NOEC for induction of vitellogenin production in male
      zebrafish was 70 and LOEC 114 MUg biochanin AL(-1). Exposure to 209 MUg biochanin
      AL(-1) from hatch to 60 days post hatch (dph) caused a skewing of the sex ratio
      toward more phenotypic female zebrafish, but did not cause induction of
      vitellogenin in male and undifferentiated fish. IN CONCLUSION: (1) biochanin A
      elicits estrogenic effects in trout at environmentally realistic concentrations,
      (2) brown trout plasma vitellogenin concentrations respond to lower biochanin A
      exposure concentrations than vitellogenin concentrations in zebrafish homogenates
      and (3) concerning vitellogenin induction, the hypothesis should be tested if
      short term tests with zebrafish may show a higher sensitivity than partial life
      cycle tests.

PMID- 24129052
TI  - Clinical outcomes of reverse total shoulder arthroplasty in patients aged younger
      than 60 years.
AB  - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has been indicated
      primarily for patients aged older than 65 years with symptomatic rotator cuff
      deficiency, poor function, and pain. However, conditions that benefit from RTSA
      are not restricted to an elderly population. This study evaluates a consecutive
      series of RTSA patients aged younger than 60 years. METHODS: We evaluated 36
      shoulders (mean age, 54 years) at a mean follow-up of 2.8 years (range, 24-48
      months). Of these shoulders, 30 (83%) had previous surgery, averaging 2.5
      procedures per patient. The preoperative conditions compelling RTSA were as
      follows: failed rotator cuff repair (12), fracture sequelae (11), failed
      arthroplasty (5), instability sequelae (4), cuff tear arthropathy (CTA) (4), and
      rheumatoid arthritis (2). Follow-up examinations included range-of-motion and
      strength testing, as well as Single Assessment Numeric Evaluation, visual analog
      scale, Simple Shoulder Test, American Shoulder and Elbow Surgeons (ASES), and
      Constant scores. Preoperative and postoperative radiographs were reviewed for
      component loosening and scapular notching. Failure criteria were defined as
      undergoing revision, having gross loosening, or having an ASES score below 50.
      RESULTS: The mean Single Assessment Numeric Evaluation score improved from 24.4
      to 72.0; the visual analog scale pain score improved from 6 to 2.1. The Simple
      Shoulder Test score improved from 1.4 to 6.2, and the ASES score improved from
      31.4 to 65.8. Active forward elevation improved from 56 degrees  to 121 degrees .
      The normalized postoperative mean Constant score was 54.3. In 9 patients (25.0%),
      we recorded an ASES score below 50, and these cases were considered failures.
      CONCLUSION: RTSA can improve shoulder function in a younger, complex patient
      population with poor preoperative functional ability. This study's success rate
      was 75% at 2.8 years. This is a limited-goals procedure, and longer-term studies
      are required to determine whether similar results are maintained over time.

PMID- 24129053
TI  - Arterial pseudoaneurysm at the arthroscopic portal site as a complication after
      arthroscopic rotator cuff surgery: a case report.

PMID- 24129054
TI  - Operative versus nonoperative treatment in the management of midshaft clavicular
      fractures: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: There is no consensus on the effects of operative versus nonoperative
      treatment on the outcomes of midshaft clavicular fractures in adults. We
      conducted a meta-analysis of randomized clinical studies. MATERIALS AND METHODS:
      We searched the literature and included studies that investigated the effects of
      operative versus nonoperative intervention on the outcome of midshaft clavicular
      fractures. Patient data were pooled by use of standard meta-analytic approaches.
      For the continuous variables, the weighted mean difference was used. For
      dichotomous data, the relative risk was calculated. RESULTS: Seven studies
      reported in 8 publications were eligible for data extraction. The pooled analyses
      showed that, compared with nonoperative treatment, operative treatment led to
      significantly lower incidences of nonunion and fewer symptomatic malunions.
      Subgroup analysis indicated that these advantages could be ascribed to plate
      fixation. Furthermore, surgery with plates resulted in significantly fewer
      complications. Patients undergoing surgery had better Disabilities of the Arm,
      Shoulder and Hand and Constant scores and lower dissatisfaction with their
      appearance. CONCLUSION: In the management of midshaft clavicular fractures,
      surgery is superior to nonoperative treatment. Surgery with plates results in
      lower incidences of nonunion, fewer total complications, and fewer symptomatic
      malunions compared with nonoperative treatment.

PMID- 24129055
TI  - Evidence of genetic variations associated with rotator cuff disease.
AB  - BACKGROUND: Rotator cuff disease (RCD) is a complex process influenced by a
      multitude of factors, and a number of gene pathways are altered in rotator cuff
      tears. Polymorphisms in these genes can lead to an extended tendon degeneration
      process, which explains why subsets of patients are more susceptible to RCD.
      MATERIALS AND METHODS: Twenty-three single-nucleotide polymorphisms within 6
      genes involved in repair and degenerative processes (DEFB1, DENND2C, ESRRB, FGF3,
      FGF10, and FGFR1) were investigated in 410 patients, 203 with a diagnosis of RCD
      and 207 presenting with absence of RCD. Exclusion criteria were patients older
      than 60 years and younger than 45 years with a history of trauma, rheumatoid
      arthritis, autoimmune syndrome, pregnancy, and use of corticosteroids. Genomic
      DNA was obtained from saliva samples. Genetic markers were genotyped with TaqMan
      real-time polymerase chain reaction. The chi(2) test compared genotypes and
      haplotype differences between groups. Multivariate logistic regression analyzed
      the significance of many covariates and the incidence of RCD. RESULTS:
      Statistical analysis revealed female sex (P = .001; odds ratio, 2.07 [1.30-3.30])
      and being white (P = .002; odds ratio, 1.88 [1.21-2.90]) to be risk factors for
      RCD development. A significant association of haplotypes CCTTCCAG in ESRRB (P =
      .05), CGACG in FGF3 (P = .01), CC in DEFB1 (P = .03), and FGFR1 rs13317 (P = .02)
      with RCD could be observed. Also, association between FGF10 rs11750845 (P = .03)
      and rs1011814 (P = .01) was observed after adjustment by ethnic group and sex.
      CONCLUSIONS: Our work clearly supports the role of DEFB1, ESRRB, FGF3, FGF10, and
      FGFR1 genes in RCD. Identification of these variants can clarify causal pathways
      and provide a clue for therapeutic targets.

PMID- 24129056
TI  - Use of the clavicular part of the pectoralis major in treatment of failed
      revision osteosynthesis of the clavicle.
AB  - BACKGROUND: Symptomatic atrophic nonunion after multiple clavicle osteosynthesis
      can be difficult to treat. The aim of this study was to evaluate the results of a
      transfer of the clavicular part of the pectoralis major muscle as augmentation of
      osteosynthesis of these nonunions. MATERIALS AND METHODS: A retrospective study
      included all patients who were treated between 2001 and 2010 (minimum 2-year
      follow-up). The indications for primary surgery, the number of operations, and
      the indication for a pectoralis major transfer were evaluated. Time of radiologic
      consolidation and postoperative complications were assessed. Clinical evaluation
      was performed with preoperative and postoperative satisfaction ratings and
      Constant-Murley scores. RESULTS: The study included 11 patients. The indications
      for a primary osteosynthesis were acute displaced fractures (7), delayed union
      (2), nonunion (1), and malunion (1). On average, 3.7 procedures were performed
      (range, 2-6) before the tendon transfer. At revision, there were 2 patients with
      infection and 9 without infection. Of the 11 clavicles, 10 showed radiologic
      consolidation after a mean time of 10 weeks (6-20 weeks). The mean follow-up was
      62 months (24-132 months). The mean Constant-Murley score increased from 37 (24
      55) preoperatively to 59 (43-98), and the satisfaction rating increased from 2 (1
      3) to 7 (2-10). Complications included nonunion (1), hardware removal (2),
      hardware irritation (4), and donor site pain (1). CONCLUSION: The use of the
      clavicular part of the pectoralis major transfer as an augmentation in revision
      for symptomatic atrophic nonunion after multiple clavicle osteosynthesis showed
      good radiologic and acceptable clinical results.

PMID- 24129057
TI  - Clinical usefulness of proximal ulnar and radial fracture-dislocation
      comprehensive classification system (PURCCS): prospective study of 39 cases.
AB  - BACKGROUND: Complex fracture-dislocations of the proximal ulna and radius
      represent a challenge even for expert orthopaedic surgeons. A new comprehensive
      classification, the proximal ulnar and radial fracture-dislocation comprehensive
      classification system (PURCCS), was recently proposed. The aim of this study was
      to analyze the clinical usefulness of this classification in a large series of
      patients. MATERIALS AND METHODS: We studied 38 patients (39 elbows) with a mean
      age of 56 years. All patients were classified with the PURCCS by use of standard
      radiography, computed tomography, and intraoperative fluoroscopy. Surgical
      treatment was performed according to the PURCCS therapeutic algorithm. Patients
      were followed up for a mean of 23 months. The clinical evaluation was performed
      with the Mayo Elbow Performance Score and Index (MEPS and MEPI); the Disabilities
      of the Arm, Shoulder, and Hand (DASH) score; and the modified American Shoulder
      and Elbow Surgeons (m-ASES) score. RESULTS: Each pattern of fracture-dislocation
      in our series finds its position within the PURCCS. At the last follow-up, the
      mean MEPS, DASH score, and m-ASES score were 91.2, 14.9, and 83.9, respectively.
      The mean extension, flexion, pronation, and supination were 19 degrees , 136
      degrees , 81 degrees , and 79 degrees , respectively. According to the MEPI, 72%,
      20%, and 8% of cases were rated excellent, good, and fair, respectively. Two
      patients with elbow stiffness underwent a reoperation, with final satisfactory
      results. CONCLUSION: The PURCCS helps identify the main lesions of each injury
      pattern; the associated therapeutic algorithm helps select correct surgical
      strategies. This study showed that the clinical results were satisfactory in the
      majority of cases, with few major complications and reinterventions. The PURCCS
      is a comprehensive classification that may contribute to the surgical management
      of these difficult fracture-dislocations. LEVEL OF EVIDENCE: Level IV, case
      series, treatment study.

PMID- 24129058
TI  - 2013 Neer Award: Effect of the adipose-derived stem cell for the improvement of
      fatty degeneration and rotator cuff healing in rabbit model.
AB  - BACKGROUND: This study was conducted to verify the effects of adipose-derived
      stem cells (ADSCs) on tendon healing and reversal of fatty infiltration in a
      chronic rotator cuff tear model by using the rabbit subscapularis (SSC). METHODS:
      The SSC insertions in 32 rabbits were cut bilaterally. After 6 weeks, secondary
      procedures were performed bilaterally, dividing the rabbits into 4 groups of 8
      rabbits each as follows: the ADSC+repair group, saline+repair group, ADSC-only
      group, and saline-only group. A fifth group of 8 rabbits served as normal
      controls (control group). Electromyographic, biomechanical, and histologic
      analyses were performed 6 weeks after the secondary procedures. RESULTS: All SSC
      tendons in the ADSC-only and saline-only groups failed to heal and were excluded
      from the electromyographic and biomechanical tests. On electromyographic
      evaluation, the ADSC+repair group exhibited a larger compound muscle action
      potential area than the saline+repair group (11.86 +/- 2.97 ms . mV vs 9.42 +/-
      3.57 ms . mV, P = .029), and this response was almost at the level of the control
      group (13.17 +/- 6.6 3 ms . mV, P = .456). Biomechanically, the load-to-failure
      of the ADSC+repair group (87.02 +/- 29.81 N) was higher than that of the
      saline+repair group (59.85 +/- 37.77 N), although this difference did not reach
      statistical significance (P = .085). Histologically, the mean proportions of
      fatty infiltration in the SSC muscles were 29% +/- 15%, 43% +/- 9%, 51% +/- 14%,
      63% +/- 10%, and 18% +/- 9% for the ADSC+repair, saline+repair, ADSC-only, saline
      only, and control groups, respectively (P < .001). The degree of fat staining
      increased from the ADSC+repair group (unclear or weak) to the saline-only group
      (strongly present). CONCLUSION: Local administration of ADSCs might have the
      possibility to improve muscle function and tendon healing and decrease fatty
      infiltration after cuff repair.

PMID- 24129060
TI  - How widespread is variant Creutzfeldt-Jakob disease?

PMID- 24129059
TI  - Prevalent abnormal prion protein in human appendixes after bovine spongiform
      encephalopathy epizootic: large scale survey.
AB  - OBJECTIVES: To carry out a further survey of archived appendix samples to
      understand better the differences between existing estimates of the prevalence of
      subclinical infection with prions after the bovine spongiform encephalopathy
      epizootic and to see whether a broader birth cohort was affected, and to
      understand better the implications for the management of blood and blood products
      and for the handling of surgical instruments. DESIGN: Irreversibly unlinked and
      anonymised large scale survey of archived appendix samples. SETTING: Archived
      appendix samples from the pathology departments of 41 UK hospitals participating
      in the earlier survey, and additional hospitals in regions with lower levels of
      participation in that survey. SAMPLE: 32,441 archived appendix samples fixed in
      formalin and embedded in paraffin and tested for the presence of abnormal prion
      protein (PrP). RESULTS: Of the 32,441 appendix samples 16 were positive for
      abnormal PrP, indicating an overall prevalence of 493 per million population (95%
      confidence interval 282 to 801 per million). The prevalence in those born in 1941
      60 (733 per million, 269 to 1596 per million) did not differ significantly from
      those born between 1961 and 1985 (412 per million, 198 to 758 per million) and
      was similar in both sexes and across the three broad geographical areas sampled.
      Genetic testing of the positive specimens for the genotype at PRNP codon 129
      revealed a high proportion that were valine homozygous compared with the
      frequency in the normal population, and in stark contrast with confirmed clinical
      cases of vCJD, all of which were methionine homozygous at PRNP codon 129.
      CONCLUSIONS: This study corroborates previous studies and suggests a high
      prevalence of infection with abnormal PrP, indicating vCJD carrier status in the
      population compared with the 177 vCJD cases to date. These findings have
      important implications for the management of blood and blood products and for the
      handling of surgical instruments.

PMID- 24129061
TI  - Isolation and molecular characterization of two lectins from dwarf elder
      (Sambucus ebulus L.) blossoms related to the Sam n1 allergen.
AB  - Sambucus species contain a number of lectins with and without antiribosomal
      activity. Here, we show that dwarf elder (Sambucus ebulus L.) blossoms express
      two D-galactose-binding lectins that were isolated and purified by affinity
      chromatography and gel filtration. These proteins, which we named ebulin blo (A-B
      toxin) and SELblo (B-B lectin)--blo from blossoms--were subjected to molecular
      characterization and analysis by MALDI-TOF mass spectrometry and tryptic peptide
      fingerprinting. Both lectins share a high degree of amino acid sequence homology
      with Sambucus lectins related to the Sam n1 allergen. Ebulin blo, but not SELblo,
      was highly toxic by nasal instillation to mice. Overall, our results suggested
      that both lectins would belong to an allergen family exemplified by Sam n1 and
      could trigger allergy responses. Furthermore, they raise a concern about ebulin
      blo toxicity.

PMID- 24129062
TI  - Real-time monitoring of oxidative stress in live mouse skin.
AB  - Oxidative stress is involved in many age-associated diseases, as well as in the
      aging process itself. The development of interventions to reduce oxidative stress
      is hampered by the absence of sensitive detection methods that can be used in
      live animals. We generated transgenic mice expressing ratiometric redox-sensitive
      green fluorescent protein (roGFP) in the cytosol or mitochondria of several
      tissues, including skin epidermal keratinocytes. Crossbreeding into hairless
      albino mice allowed noninvasive optical measurement of skin oxidative state.
      Topical application of hydrogen peroxide emulsion shifted the keratinocyte redox
      state toward oxidation within minutes and could be observed in real time by
      fluorescence ratio imaging. Exposing skin to 365 nm UVA radiation oxidized roGFP
      localized in keratinocyte mitochondria, but not when roGFP was localized in the
      cytosol. This suggests that significant amounts of the endogenous
      photosensitizers that mediate UVA-induced oxidative stress are located in the
      mitochondria. UVR is the major environmental cause of skin aging and UVA-mediated
      oxidative stress has been associated with the development of wrinkles in humans.
      Direct measurements of redox state in defined cell compartments of live animals
      should be a powerful and convenient tool for evaluating treatments that aim to
      modulate oxidative stress.

PMID- 24129063
TI  - NRAS mutation is the sole recurrent somatic mutation in large congenital
      melanocytic nevi.
AB  - Congenital melanocytic nevus (CMN) is a particular melanocytic in utero
      proliferation characterized by an increased risk of melanoma transformation
      during infancy or adulthood. NRAS and BRAF mutations have consistently been
      reported in CMN samples, but until recently results have been contradictory. We
      therefore studied a series of large and giant CMNs and compared them with small
      and medium CMNs using Sanger sequencing, pyrosequencing, high-resolution melting
      analysis, and mutation enrichment by an enhanced version of ice-COLD-PCR. Large
      giant CMNs displayed NRAS mutations in 94.7% of cases (18/19). At that point, the
      role of additional mutations in CMN pathogenesis had to be investigated. We
      therefore performed exome sequencing on five specimens of large-giant nevi. The
      results showed that NRAS mutation was the sole recurrent somatic event found in
      such melanocytic proliferations. The genetic profile of small-medium CMNs was
      significantly different, with 70% of cases bearing NRAS mutations and 30% showing
      BRAF mutations. These findings strongly suggest that NRAS mutations are
      sufficient to drive melanocytic benign proliferations in utero. 

PMID- 24129065
TI  - Somatic HRAS p.G12S mutation causes woolly hair and epidermal nevi.

PMID- 24129064
TI  - PPARgamma-mediated and arachidonic acid-dependent signaling is involved in
      differentiation and lipid production of human sebocytes.
AB  - The transcriptional basis of sebocyte differentiation and lipid production is
      mostly unclear. Peroxisome proliferator-activated receptor gamma (PPARgamma), a
      lipid-activated transcription factor, has been implicated in differentiation and
      lipid metabolism of various cell types. Here, we show that PPARgamma is
      differentially expressed in normal and pathological human sebocytes and appears
      to have roles in their differentiation and lipid production. We used laser
      microdissected normal and pathological human sebaceous glands (SGs) and SZ95
      cells (immortalized sebocyte cell line) analyzed by real-time quantitative PCR
      and immunohistochemistry. Lipids were analyzed by quantitative fluorimetry- and
      mass spectrometry-based approaches. We have observed that PPARgamma and its
      target genes, ADRP (adipose differentiation-related protein) and PGAR (PPARgamma
      angiopoietin-related protein), are expressed in sebocytes and show association
      with their level of differentiation. Also, PPARgamma is present in normal and
      hyperplastic SG, whereas its expression levels are decreased in SG adenoma and SG
      carcinoma cells, reflecting a maturation-linked expression pattern. Furthermore,
      in SZ95 sebocytes, naturally occurring lipids, including arachidonic acid and
      arachidonic acid keto-metabolites (e.g., 5-KETE (5-oxo-6E,8Z,11Z,14Z
      eicosatetraenoic acid), 12-KETE (12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid)),
      appear to regulate PPARgamma signaling pathways, which in turn modulate
      phospholipid biosynthesis and induce neutral lipid synthesis. Collectively, our
      findings highlight the importance of endogenous ligand-activated PPARgamma
      signaling in human sebocyte biology and suggest that PPARgamma might be a
      promising candidate for the clinical management of SG disorders. 

PMID- 24129066
TI  - Suppression of miR135b increases the proliferative potential of normal human
      keratinocytes.

PMID- 24129068
TI  - Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before
      and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia
      longipalpis.
AB  - In the studies presented here, dogs were vaccinated against Leishmania
      (Leishmania) chagasi challenge infection using a preparation of Leishmania
      braziliensis promastigote proteins and saponin as adjuvant (LBSap). Vaccination
      with LBSap induced a prominent type 1 immune response that was characterized by
      increased levels of interleukin (IL-) 12 and interferon gamma (IFN-gamma)
      production by peripheral blood mononuclear cells (PBMC) upon stimulation with
      soluble vaccine antigen. Importantly, results showed that this type of
      responsiveness was sustained after challenge infection; at day 90 and 885 after
      L. chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL
      12, IFN-gamma and concomitant nitric oxide (NO) when stimulated with Leishmania
      antigens as compared to PBMCs from respective control groups (saponin, LB-
      treated, or non-treated control dogs). Moreover, transforming growth factor (TGF)
      beta decreased in the supernatant of SLcA-stimulated PBMCs in the LBSap group at
      90 days. Bone marrow parasitological analysis revealed decreased frequency of
      parasitism in the presence of vaccine antigen. It is concluded that vaccination
      of dogs with LBSap vaccine induced a long-lasting type 1 immune response against
      L. chagasi challenge infection.

PMID- 24129067
TI  - Epstein-Barr virus infection induces aberrant TLR activation pathway and
      fibroblast-myofibroblast conversion in scleroderma.
AB  - Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly
      characterized by autoimmunity, vascular damage, and fibrosis that mostly involve
      the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic gamma-herpesvirus
      that has co-evolved with human species, infecting >95% of the adult population
      worldwide, and has been a leading candidate in triggering several autoimmune
      diseases. Here we show that EBV establishes infection in the majority of
      fibroblasts and endothelial cells in the skin of SSc patients, characterized by
      the expression of the EBV noncoding small RNAs (EBERs) and the increased
      expression of immediate-early lytic and latency mRNAs and proteins. We report
      that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing
      an aberrant innate immune response in infected cells. EBV-Toll-like receptor
      (TLR) aberrant activation induces the expression of selected IFN-regulatory
      factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-beta1
      (TGFbeta1), and several markers of fibroblast activation, such as smooth muscle
      actin and Endothelin-1, and all of these genes play a key role in determining the
      profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection
      occurring in mesenchymal, endothelial, and immune cells of SSc patients may
      underlie the main pathological features of SSc including autoimmunity,
      vasculopathy, and fibrosis, and provide a unified disease mechanism represented
      by EBV reactivation.

PMID- 24129069
TI  - Molecular identification of Sarcocystis aucheniae as the macrocyst-forming
      parasite of llamas.
AB  - The domestic South American camelids (SACs), llama (Lama glama) and alpaca (Lama
      paco), are frequently found to be infected with Sarcocystis parasites. Infections
      give rise in skeletal muscle to macroscopic cysts (1-5mm long) that resemble rice
      seeds, each containing several million living bradyzoites. The finding of cysts
      prevents commercialization of SAC meat, an important source of income for rural
      families in the Andean flatlands. Thus, development of diagnostic methods to
      facilitate the control of these infections is highly desirable, and the first
      step to this end is the unequivocal species identification of the causative
      agent. Based on the cyst form and size, the infecting parasite has been described
      as Sarcocystis aucheniae; however, this traditional approach is not reliable as
      similar cysts may contain different species. To date, molecular identification
      has been done for a single isolate of S. aucheniae from an alpaca in Australia.
      In order to verify the identity of the species present in SACs of South America,
      the complete 18S rRNA gene was PCR-amplified and sequenced from macrocyst DNA
      obtained from three llamas of the Andean flatlands. A phylogenetic Bayesian
      analysis was carried out using the analyzed and available 18S rRNA sequences of
      Sarcocystis spp. In the constructed tree, all of the new 18S rRNA gene sequences
      segregated in a single clade together with the 18S rRNA gene sequence reported
      from an alpaca in Australia, demonstrating that the isolated parasite is S.
      aucheniae, and that this parasite indiscriminately infects both domestic SACs.
      This work represents the first molecular identification of the causative agent of
      SAC sarcocystiosis in South America, and can contribute to the development of
      control methods for this neglected parasitosis.

PMID- 24129070
TI  - Schizothorax davidi ghrelin: cDNA cloning, tissue distribution and indication for
      its stimulatory character in food intake.
AB  - Ghrelin is a gut/brain hormone with a unique acyl modification and various
      biological functions in fish and mammals. The objectives of this project were to
      identify ghrelin gene organization, study tissue specific ghrelin mRNA expression
      and investigate the short- (0, 0.5, 1.5, 3, 6, 9, 12h post-fasting) and long- (1,
      3, 5, 7 days) term fasting as well as refeeding after a 7 day fasting induced
      changes in the expression of ghrelin mRNA in Schizothorax davidi. Our reverse
      transcription polymerase chain reaction analysis confirmed the predicted ghrelin
      sequence available in the GenBank and identified ghrelin mRNA expression in
      several tissues including the gut, liver, brain, heart, spleen, head kidney, gill
      and muscle. Quantitative PCR studies indicated that the expression level of
      ghrelin mRNA presented ascendant trend in short-term fasting group compared to
      the fed group, but it did not reach the significant level on statistics, while
      there is a significant increase in ghrelin mRNA expression in the gut of
      Schizothorax davidi fasted for 3, 5 and 7 days when compared to the expression in
      ad libitum fed fish. Refeeding after a 7 day fasting caused a significant and
      dramatic decrease in ghrelin mRNA expression in the gut of Schizothorax davidi.
      An increase in the expression of ghrelin mRNA during fasting, and its decrease
      following refeeding suggests an orexigenic role for ghrelin in Schizothorax
      davidi. Overall, our results provide evidence for a highly conserved structure
      and biological actions of ghrelin during evolution.

PMID- 24129071
TI  - De novo MECP2 duplication derived from paternal germ line result in dysmorphism
      and developmental delay.
AB  - Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males
      exhibit a distinct phenotype, including developmental delay, facial dysmorphism,
      muscular hypotonia, intellectual disability, poor or absent speech, recurrent
      infections and early death. The vast majority of affected males inherit the MECP2
      duplication from their usually asymptomatic carrier mothers. Only a few cases
      with Xq28 duplication originating from de novo unbalanced X/Y translocation have
      been reported and the paternal origin of the aberration has only been validated
      in three males in the related literature. Here we present a karyotypically normal
      male with features characteristic of the MECP2 duplication syndrome. The genome
      wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the
      terminus. The genotypes of the SNPs within the duplicated region indicated a
      paternal origin. Furthermore, the results of fluorescence in situ hybridization
      (FISH) indicated a novel Xq:Yp translocation, characterized as
      der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during
      spermatogenesis. The phenotype is compared to the previously reported cases with
      Xq28 duplication originated from an unbalanced X/Y translocation, and there was
      no specific part of the phenotype that could be contributed to the origin of
      parental imbalances. This report further highlights the capacity of high
      molecular cytogenetic methods, such as SNP array and FISH, in the identification
      of submicroscopic rearrangement, structural configuration and parental origin of
      aberrant while in the evaluation of children with idiopathic developmental delay
      and intellectual disability. 

PMID- 24129072
TI  - Data-independent acquisition (MSE) with ion mobility provides a systematic method
      for analysis of a bacteriophage structural proteome.
AB  - In this work, a method was developed to study the structural proteome of
      mycobacteriophage Marvin, a recent isolate from soil with 107 predicted coding
      sequences. This prototype method was applied for semi-quantitative analysis of
      the composition of this mycobacteriophage virion using ion mobility spectrometry
      and data-independent acquisition (MS(E)-IMS). MS(E)-IMS was compared to a more
      conventional proteomics technique employing mass spectrometry with a data
      dependent acquisition strategy. MS(E)-IMS provided broad coverage of the virion
      proteome and high sequence coverage for individual proteins. This shotgun method
      does not depend on the limited sensitivity of visualization of protein bands by
      staining reagents inherent in gel-based methods. The method is comprehensive,
      provides high sequence coverage and is proposed as a particularly efficient
      method for the study of bacteriophage proteomes. 

PMID- 24129073
TI  - Comparison of phi29-based whole genome amplification and whole transcriptome
      amplification in dengue virus.
AB  - Dengue virus is responsible for 50-100 million new infections annually worldwide.
      The virus uses error-prone RNA polymerase during genome replication in a host,
      resulting in the formation of closely related viruses known as quasispecies. The
      availability of next-generation sequencing technology provides opportunities to
      analyze viral quasispecies. Before analysis, it is crucial to increase the amount
      of DNA because of the limited amounts of viral genomic material that can be
      isolated from a patient. However, using specific primers may overlook the
      occurrence of possible variations at primer binding sites. To address this
      problem, the performance of two sequence-independent amplification methods was
      compared for whole genome amplification (WGA): phi29 DNA polymerase-based WGA and
      whole transcriptome amplification (WTA). Both methods have the ability to provide
      complete coverage of the dengue genome from template amounts as low as 1 ng.
      However, WTA showed greater efficiency in terms of yield (WTA: ~10 MUg; phi29
      based WGA: ~500 ng) and lower amplification bias. In conclusion, the WTA
      amplification kit was shown to perform substantially better than phi29 DNA
      polymerase-based WGA in terms of both final concentration and amplification bias
      in amplifying small genomes, such as that of the dengue virus.

PMID- 24129075
TI  - Probing the amino acids critical for protein oligomerisation and protein
      nucleotide interaction in Mycobacterium tuberculosis PII protein through
      integration of computational and experimental approaches.
AB  - We investigated the interacting amino acids critical for the stability and ATP
      binding of Mycobacterium tuberculosis PII protein through a series of site
      specific mutagenesis experiments. We assessed the effect of mutants using
      glutaraldehyde crosslinking and size exclusion chromatography and isothermal
      titration calorimetry. Mutations in the amino acid pair R60-E62 affecting central
      electrostatic interaction resulted in insoluble proteins. Multiple sequence
      alignment of PII orthologs displayed a conserved pattern of charged residues at
      these positions. Mutation of amino acid D97 to a neutral residue was tolerated
      whereas positive charge was not acceptable. Mutation of R107 alone had no effect
      on trimer formation. However, the combination of neutral residues both at
      positions 97 and 107 was not acceptable even with the pair at 60-62 intact.
      Reversal of charge polarity could partially restore the interaction. The residues
      including K90, R101 and R103 with potential to form H-bonds to ATP are conserved
      throughout across numerous orthologs of PII but when mutated to Alanine, they did
      not show significant differences in the total free energy change of the
      interaction as examined through isothermal titration calorimetry. The ATP binding
      pattern showed anti-cooperativity using three-site binding model. We observed
      compensatory effect in enthalpy and entropy changes and these may represent
      structural adjustments to accommodate ATP in the cavity even in absence of some
      interactions to perform the requisite function. In this respect these small
      differences between the PII orthologs may have evolved to suite species specific
      physiological niches. 

PMID- 24129074
TI  - Mutation in transforming growth factor beta induced protein associated with
      granular corneal dystrophy type 1 reduces the proteolytic susceptibility through
      local structural stabilization.
AB  - Hereditary mutations in the transforming growth factor beta induced (TGFBI) gene
      cause phenotypically distinct corneal dystrophies characterized by protein
      deposition in cornea. We show here that the Arg555Trp mutant of the fourth
      fasciclin 1 (FAS1-4) domain of the protein (TGFBIp/keratoepithelin/betaig-h3),
      associated with granular corneal dystrophy type 1, is significantly less
      susceptible to proteolysis by thermolysin and trypsin than the WT domain. High
      resolution liquid-state NMR of the WT and Arg555Trp mutant FAS1-4 domains
      revealed very similar structures except for the region around position 555. The
      Arg555Trp substitution causes Trp555 to be buried in an otherwise empty
      hydrophobic cavity of the FAS1-4 domain. The first thermolysin cleavage in the
      core of the FAS1-4 domain occurs on the N-terminal side of Leu558 adjacent to the
      Arg555 mutation. MD simulations indicated that the C-terminal end of helix
      alpha3' containing this cleavage site is less flexible in the mutant domain,
      explaining the observed proteolytic resistance. This structural change also
      alters the electrostatic properties, which may explain increased propensity of
      the mutant to aggregate in vitro with 2,2,2-trifluoroethanol. Based on our
      results we propose that the Arg555Trp mutation disrupts the normal
      degradation/turnover of corneal TGFBIp, leading to accumulation and increased
      propensity to aggregate through electrostatic interactions. 

PMID- 24129076
TI  - Challenges for red blood cell biomarker discovery through proteomics.
AB  - Red blood cells are rather unique body cells, since they have lost all organelles
      when mature, which results in lack of potential to replace proteins that have
      lost their function. They maintain only a few pathways for obtaining energy and
      reducing power for the key functions they need to fulfill. This makes RBCs highly
      sensitive to any aberration. If so, these RBCs are quickly removed from
      circulation, but if the RBC levels reduce extremely fast, this results in
      hemolytic anemia. Several causes of HA exist, and proteome analysis is the most
      straightforward way to obtain deeper insight into RBC functioning under the
      stress of disease. This should result in discovery of biomarkers, typical for
      each source of anemia. In this review, several challenges to generate in-depth
      RBC proteomes are described, like to obtain pure RBCs, to overcome the wide
      dynamic range in protein expression, and to establish which of the
      identified/quantified proteins are active in RBCs. The final challenge is to
      acquire and validate suited biomarkers unique for the changes that occur for each
      of the clinical questions; in red blood cell aging (also important for
      transfusion medicine), for thalassemias or sickle cell disease. Biomarkers for
      other hemolytic anemias that are caused by dysfunction of RBC membrane proteins
      (the RBC membrane defects) or RBC cytosolic proteins (the enzymopathies) are
      sometimes even harder to discover, in particular for the patients with RBC rare
      diseases with unknown cause. This article is part of a Special Issue entitled:
      Biomarkers: A Proteomic Challenge. 

PMID- 24129077
TI  - Chronic stress and calcium oxalate stone disease: influence on blood cortisol and
      urine composition.
AB  - OBJECTIVE: To evaluate the influence of chronic stress (CS) on urine composition
      of calcium oxalate (CaOx) stone patients and controls. METHODS: This case-control
      study enrolled 128 patients during a period of 20 months. The cases were CaOx
      stone formers with a recent stone episode. Controls were matched by sex and age.
      Dimensions of CS were evaluated in cases and controls by validated self-report
      questionnaires measuring stressful life events, perceived stress, anxiety,
      depression, burnout, and satisfaction with life. Blood and urine samples were
      collected to determine cortisol levels and urinary composition. RESULTS: More
      relations between CS dimensions and blood and urine parameters were observed in
      cases than in controls. In cases, the blood cortisol level was related positively
      with the number of stressful life events (P = .03), intensity of these events (P
      = .04), and anxiety (P = .04). In addition, urinary magnesium (P = .03) and
      pyrophosphate (P = .05) levels were positively related with satisfaction with
      life and burnout, respectively. In contrast, urinary magnesium levels were
      negatively related with perceived stress (P = .01), anxiety (P = .016), and
      depression (P = .03). In controls, the number of stressful life events and the
      intensity of stressful life events was related positively with magnesium (P =
      .06, P = .02) levels and negatively with blood cortisol levels (P = .03, P =
      .004). CONCLUSION: Based on the variation between cases and controls in relations
      between CS dimensions and biochemical parameters, we hypothesize that CS may
      trigger a differential biological response in CaOx stone formers and controls,
      which in turn may promote or protect against CaOx stone formation.

PMID- 24129078
TI  - Reply: To PMID 24129077.

PMID- 24129079
TI  - Serum leptin and 5-hydroxytryptamine measurements for the diagnosis and treatment
      of premature ejaculation.
AB  - OBJECTIVE: To study the significance of measurements of plasma leptin and 5
      hydroxytryptamine (5-HT) levels in the diagnosis of premature ejaculation (PE).
      METHODS: We compared plasma leptin and 5-HT levels, intravaginal ejaculation
      latency time (IELT) and Chinese Index of Premature Ejaculation-5 (CIPE-5) scores
      between 59 patients with PE and 64 healthy control men without PE. We then
      analyzed the correlations of plasma leptin and 5-HT levels with the IELT and CIPE
      5 scores. The patients with PE were administered sertraline (50mg daily) for 8
      weeks, and their plasma leptin and 5-HT levels, CIPE-5 scores and IELT were
      measured again. Comparative analyses of the data were performed between the
      experimental and control groups and between the pre- and post-treatment values.
      RESULTS: Plasma leptin levels were significantly higher (P <.0001), whereas
      plasma 5-HT levels (P <.0001), IELT (P <.0001), and CIPE-5 scores (P <.0001) were
      significantly lower in the experimental group than in the control group.
      Significant changes in leptin and 5-HT levels, IELT and CIPE-5 scores were
      observed after treatment in the experimental group. Plasma leptin levels
      negatively correlated with 5-HT levels, CIPE-5 scores, and IELT, whereas 5-HT
      levels positively correlated with IELT and CIPE-5 scores. CONCLUSION: Plasma
      leptin and 5-HT levels indicate the presence of PE and can be used as diagnostic
      markers for PE.

PMID- 24129080
TI  - Editorial comment.

PMID- 24129081
TI  - The allergen immunotherapy must fly to quality and beyond.

PMID- 24129082
TI  - The evolution of allergen immunotherapy from empirical desensitization to
      immunological treatment.
AB  - In its century-long history, allergen immunotherapy (AIT), has shown continuous
      evolution in terms of the materials and the treatment schedules used, the
      adequate duration, and the mechanisms of action underlying its clinical efficacy.
      The passage from the empirical phase of AIT to the era of evidence-based medicine
      (EBM) was associated with achievement of the highest levels of evidence. This
      regarded both forms of AIT currently used, represented by subcutaneous
      immunotherapy (SCIT) and sublingual immunotherapy (SLIT). In particular, SLIT
      tablet preparations of pharmaceutical quality provided physicians and patients a
      treatment whose efficacy had been confirmed with the highest level of scientific
      evidence and improved the credibility of AIT for the entire medical field.
      However, further advances are needed for AIT in terms of optimal patient
      selection and the required dosage, as well as the quality and composition of the
      allergen extracts, factors favouring compliance, and the most appropriate
      duration capable of maintaining the clinical benefit over time. 

PMID- 24129084
TI  - Towards a global vision of molecular allergology: a map of exposure to airborne
      molecular allergens.
AB  - Allergy diagnostics have changed in the last 10-15 y, moving from the use of
      extracts for in vivo and in vitro diagnosis to the Component Resolved Diagnosis,
      based on purified or recombinant allergens. As expected, aerobiology developed
      similarly, and measurement of allergens in both outdoor and indoor air is now
      feasible. With the aim of promoting a global view of molecular allergy, we have
      drawn a map of exposure to molecular aeroallergens in Italy on the bases of geo
      climatic regions, maps of pollen distribution, and published data on the
      molecular profile of sensitization in Italian patients. Given the latitudinal
      extension of Italy, the profile of exposure to some allergens, such as those of
      the "Birch Group" and weeds, varies greatly from North to South, while the
      distribution of exposure to grass allergens is more homogeneous. This map can
      contribute to a global molecular vision of allergy, helping clinicians to view
      exposure to pollen in a new way. The exposure profile of the area where patients
      live can also indicate the correct choice of molecular diagnostics and,
      therefore, of the appropriate allergen immunotherapy. 

PMID- 24129085
TI  - Molecule-based diagnosis and allergen immunotherapy.
AB  - Allergen immunotherapy (AIT) represents the only way to modify the natural
      history of allergic diseases. Unfortunately, AIT is not always followed by a
      reduction in symptoms. The main reasons for such failure can be inadequate
      diagnosis and/or the poor treatment. In both cases, an incomplete or insufficient
      understanding of the component(s) responsible for the IgE sensitization on the
      one hand, and, on the other hand, the lack of a steady and reliable allergen
      mixture to be used for the desensitization process, could explain unsuccessful
      treatment. A more comprehensive IgE reactivity profile evaluation of the patient
      can be achieved by means of a molecule-based diagnostic approach, in order to
      distinguish genuine from panallergen-driven antigen recognition. At the same
      time, a better delineation of AIT products by means of molecular dissection, can
      allow a stronger correlation between diagnostic findings and immunotherapeutic
      intervention, thus facilitating the right prescription to the right patient. 

PMID- 24129086
TI  - Advances in the quantification of relevant allergens in allergenic extracts.
AB  - Relevant allergens are major contributors to the safety and efficacy of
      allergenic extracts used in allergen immunotherapy (AIT). As such, they should be
      accurately quantified, as recommended by the 2008 European guidelines on allergen
      products. Until now, the quantification of relevant allergens was mainly
      performed by using immunoassays (e.g. ELISA) that relying upon specific
      antibodies. Although antibody-based quantification is commonly used to assess the
      concentration of relevant allergens in allergenic extracts, results must be taken
      with caution in the light of the inherent limitations of such techniques. In the
      present study, we discuss how those limitations can be overcome by using
      comprehensive mass spectrometry-based techniques. 

PMID- 24129083
TI  - Factors influencing the prescription of allergen immunotherapy: the allergen
      immunotherapy decision analysis (AIDA) study.
AB  - The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy
      has been demonstrated by a number of meta-analyses. However, the daily practice
      of AIT is quite different from controlled trials, facing challenges in terms of
      selection of patients, practical performance, and, of particular importance, use
      of allergen extracts of inadequate quality. We here performed a survey, named the
      Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are
      used by specialists to choose a product for sublingual immunotherapy (SLIT) in
      patients with respiratory allergy. A questionnaire composed of 14 items to be
      ranked by each participant according to the importance attributed when choosing
      SLIT products was submitted to 444 Italian specialists. The responses of the 169
      (38.1%) physicians, who answered all questions, were analysed. Most of the
      respondents were allergists (79%), followed by pulmonologists (10.8%), both
      allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of
      the respondents were males and 40.2% were females. The age distribution showed
      that 89.9% of the respondents were aged between 35 and 64 years. All respondents
      usually prescribed AIT products in their clinical practice: 31.4% used only SLIT,
      whereas 69.2% used both subcutaneous and sublingual administration. The rankings,
      expressed as means, attributed by physicians for each of the 14 items were as
      follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44),
      level of EBM validation of safety (4.30), standardization of the product (5.37),
      efficacy based on personal experience (5.82), defined content(s) of the major
      allergen(s) in micrograms (5.96), scientific evidence for each single allergen
      (6.17), safety based on personal experience (6.32), ease of administration
      protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose
      personalization (9.24), patient preference (9.25), ease of product storage
      (9.93), reimbursement (10.12), and availability of a helpline or on-line
      assistance from the manufacturer (11.89). These attitudes need to be taken into
      consideration by regulatory agencies as well as by producers. 

PMID- 24129087
TI  - Evaluation of stability of allergen extracts for sublingual immunotherapy during
      transport under unfavourable temperature conditions with an innovative thermal
      insulating packaging.
AB  - Many pharmaceutical and biotechnological products are temperature-sensitive and
      should normally be kept at a controlled temperature, particularly during
      transport, in order to prevent the loss of their stability and activity.
      Therefore, stability studies should be performed for temperature-sensitive
      products, considering product characteristics, typical environmental conditions,
      and anticipating environmental extremes that may occur during product transport
      in a specific country. Staloral products for sublingual immunotherapy are
      temperature sensitive and are labelled for maintenance under refrigerated
      conditions (2-8 degrees C). Given the peculiar climatic context of Italy and the
      great temperature fluctuations that may occur during transport, this study was
      aimed at evaluating the impact of a new engineered thermal insulating packaging
      for Staloral. In particular, the purpose was to assess whether the new packaging
      could create a container condition able to preserve the stability and
      immunological activity of the product during the transport phase throughout
      Italy. The results showed that the range of temperatures that can affect the
      product, in the area surrounding the product packaging, may reach a peak of 63
      degrees C during transport under the most unfavourable climatic conditions, i.e.
      in a non-refrigerated van during the summer season, from the site of production
      in France to the patient's house in Catania, the city with the highest
      temperatures in Italy. However, the highest temperature reached inside the
      vaccine did not exceed 45 degrees C over a period of about 2 h. The ELISA
      inhibition test on samples subjected to the extreme temperature conditions
      previously defined (45 degrees C) showed an immunological activity higher than
      75% of that initially measured and was comparable to those obtained with samples
      stored at controlled temperature (5 degrees C). This means that, even in the
      worst case scenario, the structure of the allergen extracts is not influenced and
      the vaccine potency is preserved. 

PMID- 24129088
TI  - Allergen immunotherapy: clinical and practical education of Italian trainees in
      allergy and clinical immunology schools.
AB  - We performed a survey, based on a questionnaire including 20 items, submitted
      anonymously to Italian trainees in Allergology and Clinical Immunology, in order
      to obtain information about their specific allergen immunotherapy (AIT)
      practices. The questionnaire was sent to 40 trainees, who had attended the last
      two years of the training course. Thirty-four subjects (mean age: 27 years, 65%
      females) adequately completed the survey. The answers to the questionnaire showed
      that only 60% of the training programs included lectures on AIT. Among the
      trainees using AIT, only 40% declared being able to prescribe it independently,
      while 60% were guided by a tutor. Of the trainees who were able to prescribe AIT
      autonomously, 60% were familiar with both routes of administration, i.e.
      subcutaneous (SCIT) and sublingual immunotherapy (SLIT), while 25% of these used
      only SLIT. In 80% of the training institutions involved, the trainees could
      attend a dedicated AIT outpatient ward for SCIT administration; only 40%
      administered AIT personally, and in half of these cases, they were guided by a
      tutor. Only 70% of trainees had experience in the follow-up of patients still
      under treatment and of patients who had completed treatment. Analysis of the
      answers obtained for questions on venom immunotherapy (VIT) showed that, in 90%
      of cases, the trainees attended a dedicated outpatients ward where VIT is
      administered, but with a role limited to observation/cooperation. Only 30% were
      involved in the follow-up of patients who were under treatment or who had
      completed VIT. Only 20% of the trainees felt confident enough about VIT to
      prescribe this treatment independently, 80% knew there were several
      administration protocols, and the majority prescribed products from three
      different manufacturers. These findings suggest that there is significant room
      for improving the instructions provided regarding allergology and clinical
      immunology to trainees in Italy with respect to AIT. 

PMID- 24129090
TI  - Amelioration of alloxan-induced diabetic keratopathy by beta-carotene.
AB  - This study was undertaken to assess the anti-keratopathy activity of beta
      carotene in experimentally-induced diabetic animal model. The rats were divided
      into four groups as following: G1, normal control group; G2, beta-carotene
      control group (50 mg/kg b.wt.); G3, diabetic group which was injected
      intraperitoneally with a single dose (100 mg/kg b. wt) of alloxan (ALX) and G4,
      diabetic rats treated with beta-carotene which was injected with ALX as G3, and
      then received a daily oral dose of beta-carotene (50 mg/kg b.wt.) for 3 months.
      ALX injection caused elevated levels of serum glucose in diabetic group.
      Moreover, histopathology revealed relatively thick corneal epithelium, ill
      defined Bowman's membrane, widely spaced stromal layers and relatively thick
      Descemet's membrane. Electron microscopic studies showed vacuolated cytoplasm,
      partial loss of hemi-desmosomes and disorganized collagen fibrils with focal
      lysis of stromal layer. Oral gavage of beta-carotene to diabetic rats for 3
      months significantly decreased serum glucose level and ameliorated
      histopathological, immunohistochemical and ultrastructural results. Consequently,
      beta-carotene exerted anti-keratopathy effects and ameliorated the corneal
      changes in diabetic rats via its hypoglycemic and antioxidant mechanisms.

PMID- 24129091
TI  - Reduced serum retinol-binding protein levels in patients with de novo acute
      myeloid leukaemia.
AB  - Retinol-binding protein (RBP) has been used as a nutritional index for children
      with acute myeloid leukaemia (AML) in previous studies. However, no studies have
      yet examined RBP levels in AML patients from all age groups. In this study, AML
      patients presented with lower RBP concentrations than healthy control subjects
      and patients with benign haematopathies. A negative association was observed
      between serum RBP level and peripheral white blood cell count in M4 and M5 AML
      patients. Moreover, patients carrying the FLT3-ITD mutation and young patients
      had lower RBP levels than those lacking this mutation and elderly patients. In
      conclusion, these observations suggest that aberrant retinol levels may be
      associated with AML. 

PMID- 24129092
TI  - VEGF depletion enhances bcr-abl-specific sensitivity of arsenic trioxide in
      chronic myelogenous leukemia.
AB  - The development of resistance to imatinib mesylate may partly depend on high bcr
      abl expression levels or point mutation(s). Arsenic trioxide (ATO) has bcr-abl
      suppressing activity in vitro, without cross-resistance to imatinib. Meanwhile,
      bcr-abl also induces expression of vascular endothelial growth factor (VEGF),
      which is associated with tumor-related angiogenesis and is involved in chronic
      myelogenous leukemia (CML) pathogenesis. Here, we investigated ways to improve
      ATO activity in CML by modulating cellular VEGF levels. K562 and primary CML
      cells were transfected with a VEGF antisense sequence. Cell viability and
      survival were assessed using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium
      bromide and trypan blue exclusion assays. Apoptotic cells were detected by flow
      cytometry following annexin V and propidium iodide staining. The results showed
      that VEGF depletion effectively promotes enhanced ATO antileukemic activity by
      repressing bcr-abl protein levels. These data provide a rationale for the
      clinical development of optimized ATO-based regimens that incorporate VEGF
      modulator for CML treatment. 

PMID- 24129093
TI  - Hereditary hemochromatosis.

PMID- 24129094
TI  - Hematology clinic: chronic myelogenous leukemia.

PMID- 24129095
TI  - New Aspidoderidae species parasite of Didelphis aurita (Mammalia: Didelphidae): a
      light and scanning electron microscopy approach.
AB  - Nematodes of the family Aspidoderidae (Nematoda: Heterakoidea) Skrjabin and
      Schikobalova, 1947, are widely distributed in the Americas. The family
      Aspidoderidae includes the subfamilies Aspidoderinae Skrjabin and Schikobalova,
      1947, and Lauroiinae Skrjabin and Schikobalova, 1951. These two subfamilies are
      delineated by the presence or absence of cephalic cordons at the anterior region.
      The nematodes in the subfamily Aspidoderinae, which includes the genus
      AspidoderaRailliet and Henry, 1912, are represented by nematodes with anterior
      cephalic cordons at the anterior end. The nematodes of the genus
      AspidoderaRailliet and Henry, 1912, are found in the cecum and large intestine of
      mammals of the orders Edentata, Marsupialia and Rodentia. Species within this
      genus have many morphological similarities. The use of scanning electron
      microscopy allows the specific characterization of the species within this genus.
      In the present work, we describe a new species of Aspidodera parasite of the
      large intestine of Didelphis aurita (Mammalia: Didelphidae) Wied-Neuwied, 1826,
      collected from Cachoeiras de Macacu, Rio de Janeiro. The combination of light and
      scanning electron microscopy allowed us a detailed analysis of this nematode. 

PMID- 24129096
TI  - A pencil rescues impaired performance on a visual discrimination task in patients
      with medial temporal lobe lesions.
AB  - We tested proposals that medial temporal lobe (MTL) structures support not just
      memory but certain kinds of visual perception as well. Patients with hippocampal
      lesions or larger MTL lesions attempted to identify the unique object among twin
      pairs of objects that had a high degree of feature overlap. Patients were
      markedly impaired under the more difficult task conditions. However, the deficit
      was fully rescued when patients used a pencil to draw lines between the twin
      pairs, thereby eliminating the need to hold material in memory as they worked at
      each display. The perceptual demands of the task were presumably the same with or
      without this memory aid. Accordingly, the results suggest that the deficit on
      this and similar tasks, which involve comparisons across stimuli, are better
      understood in terms of impaired memory rather than impaired perception. 

PMID- 24129097
TI  - Hippocampal structural plasticity accompanies the resulting contextual fear
      memory following stress and fear conditioning.
AB  - The present research investigated the resulting contextual fear memory and
      structural plasticity changes in the dorsal hippocampus (DH) following stress and
      fear conditioning. This combination enhanced fear retention and increased the
      number of total and mature dendritic spines in DH. Intra-basolateral amygdala
      (BLA) infusion of midazolam prior to stress prevented both the enhancement of
      fear retention and an increase in the density of total and mature dendritic
      spines in DH. These findings emphasize the role of the stress-induced attenuation
      of GABAergic neurotransmission in BLA in the promoting influence of stress on
      fear memory and on synaptic remodeling in DH. In conclusion, the structural
      remodeling in DH accompanied the facilitated fear memory following a combination
      of fear conditioning and stressful stimulation. 

PMID- 24129099
TI  - Thalassaemic osteopathy: a cross-sectional preliminary study from Sri Lanka.
AB  - INTRODUCTION: The objectives of this study were to demonstrate the presence of
      low bone mineral density (BMD) and to examine the association of known risk
      factors for low BMD in patients with beta thalassaemia major in Sri Lanka.
      METHOD: Thirty-eight patients were studied. Their examination and laboratory
      investigation findings were recorded (haematology, biochemistry, hormonal
      profile, COL1A1 rs1800012G>T genotype, dual energy X-ray absorptiometry (DXA)
      scanning). RESULTS: Mean age was 10.95 years (range 5-21.4). 20 (52.6%) were
      male. BMD was low (z score <=-2.0) in 12 (31.5%). Regression analysis of BMD on
      known risk factors (age, sex, pubertal stage, ferritin level, average pre
      transfusion haemoglobin, serum calcium level and COL1A1 rs1800012G>T genotype)
      controlling for confounding factors on each comparison, showed that only age was
      significantly associated with low BMD (p=0.005). CONCLUSIONS: Approximately one
      third of patients had a low BMD. Only age was significantly associated with a low
      BMD.

PMID- 24129100
TI  - Pituitary stalk lesion in a 13-year-old female.
AB  - Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are
      rare in children, and their definite diagnosis is challenging. An invasive
      diagnostic approach, such as a transsphenoidal biopsy, is often required prior to
      establishing a treatment regimen. A 13-year-old female presented with 1 year of
      secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory
      work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic
      hypogonadism, adrenal insufficiency and central diabetes insipidus). alpha
      Fetoprotein and beta-human chorionic gonadotropin were not elevated in serum nor
      in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary
      region showed an enhancing infundibular lesion, extending into the hypothalamus,
      and infiltrating the pituitary gland. A transsphenoidal biopsy of the
      infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After
      appropriate hormone replacement therapy, chemotherapy and low-dose radiation
      therapy, the patient achieved complete resolution of the pituitary stalk lesion
      on the MRI.

PMID- 24129098
TI  - Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive
      abilities and is modulated by working memory training.
AB  - A common source of variance (i.e., "general intelligence") underlies an
      individual's performance across diverse tests of cognitive ability, and evidence
      indicates that the processing efficacy of working memory may serve as one such
      source of common variance. One component of working memory, selective attention,
      has been reported to co-vary with general intelligence, and dopamine D1 signaling
      in prefrontal cortex can modulate attentional abilities. Based on their aggregate
      performance across five diverse tests of learning, here we characterized the
      general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist
      (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation
      of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial
      prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum.
      Increased activation of D1R-containing neurons in the prelimbic cortex (but not
      the agranular insular cortex or dorsomedial striatum) was observed in animals of
      high GCA relative to those of low GCA (quantified by c-Fos activation in response
      to the D1 agonist). However, a Western blot analysis revealed no differences in
      the density of D1Rs in the prelimbic cortex between animals of high and low GCA.
      Last, it was observed that working memory training promoted an increase in
      animals' GCA and enhanced D1R-mediated neuronal activation in the prelimbic
      cortex. These results suggest that the sensitivity (but not density) of D1Rs in
      the prelimbic cortex may both regulate GCA and be a target for working memory
      training. 

PMID- 24129101
TI  - NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.
AB  - Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism,
      respiratory distress syndrome, and benign hereditary chorea is caused by thyroid
      transcription factor 1 (NKX2-1/TTF1) mutations. We report the clinical and
      molecular characteristics of four cases presenting with primary hypothyroidism,
      respiratory distress, and neurological disorder. Two of the four patients
      presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1
      [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without
      any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this
      raises the possibility of mitochondrial mutations contributing to thyroid
      dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological,
      and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for
      NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities
      will enable a unifying diagnosis and genetic counseling for the affected
      families. In addition, identification of an NKX2-1 defect would be helpful in
      allaying the concerns about inadequate thyroxine supplementation as the cause of
      neurological defects observed in some children with congenital hypothyroidism.

PMID- 24129102
TI  - Age of onset of pubertal maturation of Thai boys.
AB  - BACKGROUND: Data regarding sexual maturation in Thai boys are limited to only one
      1999 study done in Bangkok which found that the ages of onset of Tanner 2
      testicular enlargement and pubic hair were 10.8 and 12.4 years, respectively.
      OBJECTIVE: To determine the age of onset of pubertal maturation and the physical
      growth of Thai boys at Hat Yai municipality, southern Thailand, in the year 2012.
      METHODS: A cross-sectional study was conducted in 1320 healthy boys, aged 6-19
      years, during June 2011 to March 2012. Testicular volume and pubic hair
      development were assessed according to the Tanner staging method. Probit analysis
      was used to calculate the median age of different stages of testicular
      enlargement and pubic hair development. RESULTS: The median ages of boys having
      Tanner 2 testicular enlargement and Tanner 2 pubic hair were 10.6 [95% confidence
      interval (CI), 10.4-10.7] and 12.0 (95% CI, 11.8-12.2) years, respectively. The
      youngest ages of boys who had Tanner 2 testicular enlargement and Tanner 2 pubic
      hair were 8.2 and 9.7 years, respectively. The final height was attained at age
      18 years at 170.3 cm, 3.3 cm greater than the 167.0 cm final height of Hat Yai
      boys studied in 1994. CONCLUSIONS: The age of onset of puberty in Hat Yai
      schoolboys in 2012 was 0.2 years earlier than that of Bangkok schoolboys in 1999.
      The final adult height of Thai boys increased 3 cm during the two decades.

PMID- 24129103
TI  - Present status and perspective of pharmacogenetics in Mexico.
AB  - Drug costs account for up to 24% of the country's health expenditure and there
      are 13,000 registered drugs being prescribed. Diabetes is the main cause of death
      in the country, with over 85% of diabetic patients currently under drug
      treatment. The importance of knowing interindividual variability in drug
      metabolism on Mexican populations is thus evident. The purpose of this article is
      to provide an overlook of the current situation of pharmacogenetic research in
      Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing
      a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic
      studies on Mexican population samples (Mestizos and Amerindian) have been
      published. These have reported interindividual variability through phenotyping
      and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT
      and NAT2. Some cytochromes with important clinical implications have not yet been
      phenotyped in Mexican populations. The development of a cocktail adapted to them
      could be a significant contribution to a larger knowledge on drug response
      variability at a lower price and shorter time. There are validated phenotyping
      cocktails that present several practical advantages, being valuable, safe, and
      inexpensive tools in drug metabolism characterization, which require only a
      single experiment to provide information on several cytochrome activities.

PMID- 24129104
TI  - Augmented primary humoral immune response and decreased cell-mediated immunity by
      Murraya koenigii in rats.
AB  - BACKGROUND: Murraya koenigii (Rutaceae) (curry patta: Hindi) of the family
      Rutaceae is used in the traditional Indian system of medicine for its
      immunomodulatory properties. The essential oil of the leaves of M. koenigii
      possesses antimicrobial, antifungal, and pesticidal activities and is used for
      the treatment of amebiasis, diabetes, and hepatitis. The present study was
      performed to evaluate the effect of M. koenigii on humoral and cell-mediated
      immune responses in rats. METHODS: Aqueous extract of M. koenigii leaves was
      administered orally in a dose of 350 mg/kg. Cell-mediated immunity was assessed
      by measuring foot pad thickness following sensitization by injection of keyhole
      limpet hemocyanin and subsequent challenge by the same. Humoral immunity was
      assessed by measurement of hemagglutination titer to sheep red blood cells
      (SRBCs). RESULTS: In the humoral immune response, the administration of M.
      koenigii [350 mg/kg per os (p.o.)] from day 1 to day 7 after sensitization with
      SRBC on day 0 caused a significant increase in the primary anti-SRBC titer.
      However, the secondary immune response was decreased significantly (p<0.05) as
      shown by a decrease in secondary anti-SRBC titer measured on day 11 following a
      booster dose of antigen on day 8. In the delayed-type hypersensitivity test, M.
      koenigii (350 mg/kg, p.o.), when administered for 14 days, produced a significant
      (p<0.05) decrease in foot pad thickness when compared with the control group.
      CONCLUSIONS: Thus, these results suggest that oral administration of M. koenigii
      augments primary humoral immune response and decreases cell-mediated immunity.

PMID- 24129105
TI  - Highlight: perspectives in molecular neurobiology.

PMID- 24129106
TI  - Reference values of fetal serum beta2-microglobulin in the Chinese: evaluation of
      its clinical usefulness.
AB  - BACKGROUND: The level of beta2-microglobulin was generally used to evaluate the
      renal function in adults. Elevated levels of beta2-microglobulin were also
      applied to assess the perinatal situations in neonates and fetuses. The aim of
      our study was to establish and determine the reference values of fetal serum
      beta2-microglobulin in the Chinese and to assess its clinical benefits in
      abnormal fetuses. METHODS: Data from 308 normal cord blood samples were obtained
      to calculate the normal reference values of fetal serum beta2-microglobulin.
      According to the equations we obtained, we analyzed the level of beta2
      microglobulin in four case groups: renal malformation, hydrops, cytomegalovirus
      (CMV) infection and rubella virus (RV) infection. RESULTS: In the normal group,
      the concentration of beta2-microglobulin decreased with the gestational age, with
      a mean value of 4.35+/-0.59 mg/L. The upper limit of beta2-microglobulin was
      calculated as 7.55-0.074*gestational age in weeks. The levels of beta2
      microglobulin were significantly higher in the four case groups than the normal
      group. For the four groups, the sensitivity is 72.7%, 69.6%, 86.7% and 100%,
      respectively. CONCLUSIONS: Fetal serum beta2-microglobulin may be used as a
      predictor to evaluate the situations of fetal diseases.

PMID- 24129107
TI  - Review of the current knowledge on the epidemiology, pathogenesis, and prevention
      of human papillomavirus infection.
AB  - Human papillomavirus (HPV) infection is a central and necessary, although not
      sufficient, cause of cervical cancer. Besides HPV, the additional multiple risk
      factors related with the onset of cervical cancer are early-age sexual
      activities; high number of sexual partners, which is the most salient risk
      factor; suppression and alteration of the immune status; long-term use of oral
      contraceptives; and other hormonal influences. The tumor-suppressor proteins p53
      and pRb are degraded and destabilized through ubiquitination by viral
      oncoproteins E6 and E7. Over 95% of cervical cancer cases worldwide test positive
      for oncogenic HPV DNA. Although cervical screening procedures have been
      successful in reducing the disease burden associated with HPV infection because
      of lack of resources or inadequate infrastructure many countries have failed to
      reduce cervical cancer mortality. Therefore, prevention may be a valuable
      strategy for reducing the economic and disease burden of HPV infection. At
      present, two successful prophylactic HPV vaccines are available, quadrivalent
      (HPV16/18/6/11) 'Gardasil' and bivalent (HPV16/18) 'Cervarix' for vaccinating
      young adolescent girls at or before the onset of puberty. Recent data indicate
      that vaccination prevents the development of cervical lesions in women who have
      not already acquired the vaccine-specific HPV types. Moreover, several
      therapeutic vaccines that are protein/peptide-based, DNA-based, or cell-based are
      in clinical trials but are yet to establish their efficacy; these vaccines are
      likely to provide important future health benefits. The therapeutic vaccination
      mode of prevention is a promising area of research, as revealed in preclinical
      trials; however, clinical trials based on large populations are warranted before
      reaching a valid conclusion. This review summarizes the studies on the
      epidemiology of HPV infection, the pathogenesis of viral oncoproteins in the
      oncogenesis of cervical cancer, the economic and health burden of HPV-related
      diseases, and, finally, focuses on the results of recent clinical vaccination
      trials. 

PMID- 24129108
TI  - Stem cell derived tissues and microphysiological systems: a paradigm shifting
      moment.

PMID- 24129109
TI  - Veterinary applications of induced pluripotent stem cells: regenerative medicine
      and models for disease?
AB  - Induced pluripotent stem cells (iPSCs) can now be derived from a tissue biopsy
      and represent a promising new platform for disease modelling, drug and toxicity
      testing, biomarker development and cell-based therapies for regenerative
      medicine. In regenerative medicine, large animals may represent the best models
      for man, and thereby provide invaluable systems in which to test the safety and
      the potential of iPSCs. Hence, testing iPSCs in veterinary species may serve a
      double function, namely, developing therapeutic products for regenerative
      medicine in veterinary patients while providing valuable background information
      for human clinical trials. The production of iPSCs from livestock or wild species
      is attractive because it could improve efficiency and reduce costs in various
      fields, such as transgenic animal generation and drug development, preservation
      of biological diversity, and because it also offers an alternative to
      xenotransplantation for in vivo generation of organs. Although the technology of
      cellular reprogramming using the so-called 'Yamanaka factors' is in its peak
      expectation phase and many concerns still need to be addressed, the rapid
      technical progress suggests that iPSCs could contribute significantly to novel
      therapies in veterinary and biomedical practice in the near future. This review
      provides an overview of the potential applications of iPSCs in veterinary
      medicine. 

PMID- 24129111
TI  - Deep brain stimulation for Parkinson's disease with early motor complications.

PMID- 24129110
TI  - Thermal nociception as a measure of non-steroidal anti-inflammatory drug
      effectiveness in broiler chickens with articular pain.
AB  - Pain associated with poultry lameness is poorly understood. The anti-nociceptive
      properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated
      using threshold testing in combination with an acute inflammatory arthropathy
      model. Broilers were tested in six groups (n=8 per group). Each group underwent a
      treatment (saline, meloxicam (3 or 5mg/kg) or carprofen (15 or 25mg/kg)) and a
      procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to
      testing. Induced groups had Freund's complete adjuvant injected intra-articularly
      into the left intertarsal joint (hock). A ramped thermal stimulus (1 degrees C/s)
      was applied to the skin of the left metatarsal. Data were analysed using random
      intercept multi-level models. Saline-induced birds had a significantly higher
      skin temperature (+/- SD) than saline-sham birds (37.6 +/- 0.8 degrees C vs. 36.5
      +/- 0.5 degrees C; Z=-3.47, P<0.001), consistent with an inflammatory response.
      Saline was associated with significantly lower thermal thresholds (TT) than
      analgesic treatment (meloxicam: Z=2.72, P=0.007; carprofen: Z=2.58, P=0.010) in
      induced birds. Saline-induced birds also had significantly lower TT than saline
      sham birds (Z=-2.17, P=0.030). This study found direct evidence of an association
      between inflammatory arthropathies and thermal hyperalgesia, and showed that
      NSAID treatment maintained baseline thermal sensitivity (via anti-nociception).
      Quantification of nociceptive responsiveness in a predictable broiler pain model
      identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested
      that therapeutically effective treatment was provided at the doses administered.
      Such validation of analgesic strategies will increase the understanding of pain
      associated with specific natural broiler lameness types.

PMID- 24129112
TI  - Brimonidine gel (Mirvaso) for rosacea.

PMID- 24129113
TI  - In brief: Buprenorphine/naloxone (Zubsolv) for opioid dependence.

PMID- 24129114
TI  - Respiratory disease related mortality and morbidity on an island of Greece
      exposed to perlite and bentonite mining dust.
AB  - A morbidity and mortality study took place, focused on Milos Island, where
      perlite and bentonite mining sites are located. Official data concerning number
      and cause of deaths, regarding specific respiratory diseases and the total of
      respiratory diseases, for both Milos Island and the Cyclades Prefecture were
      used. Standardized Mortality Ratios (SMRs) were computed, adjusted specifically
      for age, gender and calendar year. Tests of linear trend were performed. By means
      of a predefined questionnaire, the morbidity rates of specific respiratory
      diseases in Milos, were compared to those of the municipality of Oinofita, an
      industrial region. Chi-square analysis was used and the confounding factors of
      age, gender and smoking were taken into account, by estimating binary logistic
      regression models. The SMRs for Pneumonia and Chronic Obstructive Pulmonary
      Disease (COPD) were found elevated for both genders, although they did not reach
      statistical significance. For the total of respiratory diseases, a statistically
      significant SMR was identified regarding the decade 1989-1998. The morbidity
      study revealed elevated and statistically significant Odds Ratios (ORs),
      associated with allergic rhinitis, pneumonia, COPD and bronchiectasis. An
      elevated OR was also identified for asthma. After controlling for age, gender and
      smoking, the ORs were statistically significant and towards the same direction. 

PMID- 24129115
TI  - Improving the psychosocial work environment at multi-ethnic workplaces: a multi
      component intervention strategy in the cleaning industry.
AB  - Global labour migration has increased in recent years and immigrant workers are
      often recruited into low status and low paid jobs such as cleaning. Research in a
      Danish context shows that immigrants working in the cleaning industry often form
      social networks based on shared languages and backgrounds, and that conflict
      between different ethnic groups may occur. This paper evaluates the impact of a
      multi-component intervention on the psychosocial work environment at a multi
      ethnic Danish workplace in the cleaning sector. The intervention included Danish
      lessons, vocational training courses, and activities to improve collaboration
      across different groups of cleaners. Interviews about the outcome of the
      intervention were conducted with the cleaners and their supervisor. The
      Copenhagen Psychosocial Questionnaire was used as a supplement to the interviews.
      The results suggest that the psychosocial work environment had improved after the
      intervention. According to the interviews with the cleaners, the intervention had
      led to improved communication, trust, and collaboration. These findings are
      supported by the questionnaire where social support from supervisor and
      colleagues, social community, trust, and teamwork seem to have improved together
      with meaning of work, rewards, and emotional demands. The design of the
      intervention may provide inspiration for future psychosocial work environment
      interventions at multi-ethnic work places. 

PMID- 24129116
TI  - Spatially interpolated disease prevalence estimation using collateral indicators
      of morbidity and ecological risk.
AB  - This paper considers estimation of disease prevalence for small areas
      (neighbourhoods) when the available observations on prevalence are for an
      alternative partition of a region, such as service areas. Interpolation to
      neighbourhoods uses a kernel method extended to take account of two types of
      collateral information. The first is morbidity and service use data, such as
      hospital admissions, observed for neighbourhoods. Variations in morbidity and
      service use are expected to reflect prevalence. The second type of collateral
      information is ecological risk factors (e.g., pollution indices) that are
      expected to explain variability in prevalence in service areas, but are typically
      observed only for neighbourhoods. An application involves estimating
      neighbourhood asthma prevalence in a London health region involving 562
      neighbourhoods and 189 service (primary care) areas. 

PMID- 24129117
TI  - Depressive symptoms and its associated factors in 13-year-old urban adolescents.
AB  - The available estimates reveal that 20-50% of adolescents report depressive
      symptoms, being one of the most prevalent health problems in adolescence. The aim
      of this study was to assess the prevalence of depressive symptoms in a community
      sample of 13-year-old adolescents and identify associated features. Thirteen year
      old adolescents attending private and public schools in Porto (n = 1,988, 52.2%
      females) were evaluated from October 2003 to June 2004 and completed a
      questionnaire including health behaviors and the Beck Depression Inventory II. A
      questionnaire on parents' socio-demographics and clinical characteristics was
      sent home. Data were analyzed separately by sex. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were estimated using logistic regression. The
      prevalence of depressive symptoms was 18.8% in girls and 7.6% in boys (p <
      0.001). Boys with a family history of depression and girls with smoking habits
      had a significantly increased risk of depressive symptoms (OR = 2.18, 95%CI 1.00
      4.71; OR = 2.34, 95%CI 1.46-3.76). Menarche at an early age significantly
      increased the risk of depressive symptoms. The characteristics most strongly
      associated with depressive symptoms were family history of depression among boys,
      tobacco consumption and an early age at menarche among girls. The high prevalence
      of depressive symptoms early in adolescence calls for the awareness of public
      health professionals. 

PMID- 24129118
TI  - Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I
      like receptors: hide, mask, hit.
AB  - Double-stranded RNA (dsRNA) is synthesized during the course of infection by RNA
      viruses as a byproduct of replication and transcription and acts as a potent
      trigger of the host innate antiviral response. In the cytoplasm of the infected
      cell, recognition of the presence of viral dsRNA as a signature of "non-self"
      nucleic acid is carried out by RIG-I-like receptors (RLRs), a set of dedicated
      helicases whose activation leads to the production of type I interferon
      alpha/beta (IFN-alpha/beta). To overcome the innate antiviral response, RNA
      viruses encode suppressors of IFN-alpha/beta induction, which block RLRs
      recognition of dsRNA by means of different mechanisms that can be categorized
      into: (i) dsRNA binding and/or shielding ("hide"), (ii) dsRNA termini processing
      ("mask") and (iii) direct interaction with components of the RLRs pathway
      ("hit"). In light of recent functional, biochemical and structural findings, we
      review the inhibition mechanisms of RLRs recognition of dsRNA displayed by a
      number of highly pathogenic RNA viruses with different disease phenotypes such as
      haemorrhagic fever (Ebola, Marburg, Lassa fever, Lujo, Machupo, Junin, Guanarito,
      Crimean-Congo, Rift Valley fever, dengue), severe respiratory disease (influenza,
      SARS, Hendra, Hantaan, Sin Nombre, Andes) and encephalitis (Nipah, West Nile). 

PMID- 24129119
TI  - Yokukansan, a traditional Japanese herbal medicine, alleviates the emotional
      abnormality induced by maladaptation to stress in mice.
AB  - The aim of the present study was to examine the effect of yokukansan, a
      traditional Japanese herbal medicine that is composed of Atractylodis lanceae
      Rhizoma, Poria, Cnidii Rhizoma, Uncariae Uncis cum Ramulus, Angelicae Radix,
      Bupleuri Radix and Glycyrrhizae Radix, on the emotional abnormality induced by
      maladaptation to stress in mice. Mice were exposed to repeated restraint stress
      for 60 or 240 min/day for 14 days. From the 3rd day of stress exposure, mice were
      given yokukansan orally (p.o.) or the 5-HT1A receptor agonist flesinoxan
      intraperitoneally (i.p.) immediately after the daily exposure to restraint
      stress. After the final exposure to restraint stress, the emotionality of mice
      was evaluated using an automatic hole-board apparatus. A single exposure to
      restraint stress for 60 min induced a decrease in head-dipping behavior in the
      hole-board test. This emotional stress response disappeared in mice that had been
      exposed to repeated restraint stress for 60 min/day for 14 days, which confirmed
      the development of stress adaptation. In contrast, mice that were exposed to
      restraint stress for 240 min/day for 14 days did not develop this stress
      adaptation, and still showed a decrease in head-dipping behavior. The decreased
      emotionality observed in stress-maladaptive mice was significantly recovered by
      chronic treatment with yokukansan (1000 mg/kg, p.o.) as well as flesinoxan (0.25
      and 0.5 mg/kg, i.p.) immediately after daily exposure to stress. These findings
      suggest that yokukansan may have a beneficial effect on stress adaptation and
      alleviate the emotional abnormality under conditions of excessive stress.

PMID- 24129120
TI  - On-particle detection of Plasmodium falciparum histidine-rich protein II by a
      "switch-on" iridium(III) probe.
AB  - The need for robust reagents for biomarker detection has become an increasing
      necessity in designing point-of-care diagnostics. We report a non-emissive,
      cyclometalated iridium(III) complex, Ir(ppy)2(H2O)2(+) (Ir1), which, on
      coordination to a histidine-containing protein bound to the surface of a magnetic
      particle, elicits a rapid, long-lived phosphorescent signal. The interactions
      between Ir1 and numerous other amino acids were examined for activity, but only
      the addition of histidine resulted in a four orders of magnitude enhancement in
      signal intensity. Buffer conditions (pH and temperature) and composition
      (coordinating vs. non-coordinating and ionic strength) were optimized to achieve
      maximum signal and stability of Ir1. The activity of the probe under optimized
      conditions was validated with BNT-II, a histidine-containing branched peptide
      mimic of the malarial biomarker Plasmodium falciparum histidine-rich protein II
      (PfHRPII). By comparing Ir1 binding to BNT-II versus L-histidine, steric and
      quenching effects were noted in the peptide. Despite these deviations from ideal
      conditions, signal response reached saturation with both BNT-II and recombinant
      HRPII (rcHRPII). When immobilized on the surface of a 50 MUM magnetic agarose
      particles, the limit of detection of rcHRPII was 14.5 nM. The robust signal
      response of this inorganic probe lends itself to future applications in on
      particle enzyme-linked immunosorbent assay (ELISA)-based assays.

PMID- 24129121
TI  - Phosphorus deficiency affects the allocation of below-ground resources to
      combined cluster roots and nodules in Lupinus albus.
AB  - Lupins can rely on both cluster roots and nodules for P acquisition and
      biological nitrogen fixation (BNF), respectively. The resource allocation (C, N
      and P) between cluster roots and nodules has been largely understudied during P
      deficient conditions. The aim of this investigation was therefore to determine
      the changes in resource allocation between these organs during fluctuations in P
      supply. Lupinus albus was cultivated in sand culture for 3 weeks, with either
      sufficient (2 mM high) or limiting (0.1 mM low) P supply. Although variation on P
      supply had no effect on the total biomass, there were significant differences in
      specialised below-ground organ allocation to cluster roots and nodule formation.
      Cluster root formation and the associated C-costs increased during low P supply,
      but at sufficient P-supply the construction and growth respiration costs of
      cluster roots declined along with their growth. In contrast to the cluster root
      decline at high P supply, there was an increase in nodule growth allocation and
      corresponding C-costs. However, this was not associated with an increase in BNF.
      Since cluster roots were able to increase P acquisition under low P conditions,
      this below-ground investment may also have benefited the P nutrition of nodules.
      These findings provide evidence that when lupins acquire N via BNF in their
      nodules, there may be a trade-off in resource allocation between cluster roots
      and nodules.

PMID- 24129122
TI  - Maxillary neurilemmoma-Rarest of the rare tumour: Report of 2 cases.
AB  - INTRODUCTION: Intraoral neurilemmomas (schwannoma) are rare, even rarer are
      intraosseous ones, and the rarest are the maxillary neurilemmomas. Going by the
      literature only 5 cases of maxillary neurilemomas are reported till now.
      Neurilemmomas are benign tumours of nerve sheath origin. Approximately 30% arise
      in head and neck region, of these 1-12% arise intraorally mainly involving
      tongue. PRESENTATION OF CASE: Here we report two cases of maxillary neurilemmoma,
      one in a 9 year old girl and second one in a 27 year old female, both involving
      the lateral surface of maxilla on right side. Both the patients presented with a
      long standing history of swelling which was increasing gradually. 9-Year-old girl
      also had 1 lesion in the temporal region on right side and the 27-year-old
      patient had associated erosion of the soft palate. Diagnosis was made on the
      basis of histopathology and immunohistochemistry. DISCUSSION: Neurilemmomas are
      slow growing benign tumour of the nerve sheath origin arising from the Schwann
      cells. Their aetiology is not known. Most common complaint is that of a gradually
      increasing swelling followed by pain and paresthesias. Surgery remains the
      treatment of choice with close follow up. CONCLUSION: Maxillary neurilemmomas are
      rarest of the rare tumour which closely mimic benign odontogenic cysts and
      tumours, and should be kept in the differential diagnosis of these lesions.
      Knowledge of the radiologic and clinical behaviour of these tumours is extremely
      important for prompt diagnosis and treatment.

PMID- 24129124
TI  - Tumour size and differentiation predict survival after liver resection for
      hepatocellular carcinoma arising from non-cirrhotic and non-fibrotic liver: a
      case-controlled study.
AB  - AIMS: The aims of this study were to assess the outcomes of patients who
      underwent potentially curative hepatic resection for hepatocellular carcinoma
      (HCC) in a background of non-cirrhotic/non-fibrotic livers, and to determine
      prognostic factors that influenced survival. METHODS: Over a 15-year period, all
      patients undergoing hepatectomy for HCC were identified. Collated data included
      demographics, laboratory analysis, operative findings and histo-pathological
      data. Survival differences between these factors following liver resection were
      determined. RESULTS: 57 patients were included with a median age of 70 years. The
      majority of patients underwent a hemi-hepatectomy or more radical resection (n =
      37). Overall R0 resection rate was 90.4% (n = 51). The overall morbidity and
      mortality rates were 26.3% and 3.5%, respectively. The median follow-up period
      was 28 months. The 1-, 3- and 5- year disease-free survival was 65.4%, 41.8% and
      39.1%, and the overall survival was 73.5%, 49.6% and 39.5%, respectively. AFP (p
      = 0.039) was the only predictor of poorer disease-free survival on univariate
      analysis. On multi-variable analysis, poorly differentiated tumour and large
      tumour size were independent predictors of overall survival. CONCLUSIONS: Liver
      resection is a feasible treatment option for HCC in non-cirrhotic/non-fibrotic
      livers with good survival outcome. Tumour size and differentiation are adverse
      predictors of outcome in these patients.

PMID- 24129123
TI  - Priorities for CMV vaccine development.
AB  - A multidisciplinary meeting addressed priorities related to development of
      vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV)
      disease and of serious disease in the immunocompromised. Participants discussed
      optimal uses of a CMV vaccine, aspects of clinical study design, and the value of
      additional research. A universal childhood CMV vaccine could potentially rapidly
      reduce cCMV disease, as infected children are sources of viral transmission to
      seronegative and seropositive mothers. A vaccine administered to adolescents or
      adult women could also reduce cCMV disease by making them immune prior to
      pregnancy. Clinical trials of CMV vaccines in women should evaluate protection
      against cCMV infection, an essential precursor of cCMV disease, which is a more
      practical and acceptable endpoint for assessing vaccine effects on maternal-fetal
      transmission. Clinical trials of vaccines to evaluate prevention of CMV disease
      in stem cell transplant recipients could use CMV viremia at a level triggering
      pre-emptive antiviral therapy as an endpoint, because widespread use of pre
      emptive and prophylactic antivirals has rendered CMV-induced disease too rare to
      be a practical endpoint for clinical trials. In solid organ transplant patients,
      CMV-associated disease is sufficiently common for use as a primary endpoint.
      Additional research to advance CMV vaccine development should include identifying
      factors that predict fetal loss due to CMV, determining age-specific incidence
      and transmission rates, defining the mechanism and relative contributions of
      maternal reactivation and re-infection to cCMV disease, developing assays that
      can distinguish between reactivation and re-infection in seropositive vaccinees,
      further defining predictors of sequelae from cCMV infection, and identifying
      clinically relevant immune response parameters to CMV (including developing
      validated assays that could assess CMV antibody avidity) that could lead to the
      establishment of immune correlates of protection. 

PMID- 24129125
TI  - Differential tumor expression of inhibitor of differentiation-1 in prostate
      cancer patients with extreme clinical phenotypes and prognostic implications.
AB  - BACKGROUND: In the prostate-specific antigen era, potentially indolent prostate
      tumors are radically treated, causing overtreatment. Molecular prognostic factors
      might differentiate indolent from aggressive tumors, allowing avoidance of
      unnecessary treatment. PATIENTS AND METHODS: Fifty-two prostate cancer patients
      (20 organ-confined and 32 metastatic) were selected. All formalin-fixed and
      paraffin-embedded primary biopsies and matched metastases of 15 of them were
      evaluated for tumor and endothelial cell Id1 protein expression. Seventy-nine
      additional patients with organ-confined prostate cancer were selected for Id1
      mRNA in silico analysis. RESULTS: Among metastatic cancer subjects, 48% of
      primary tumors and 38% of metastases showed Id1 tumor cell expression, and 79% of
      primary tumors and 81% of metastases showed endothelial immunoreactivity. In the
      organ-confined group none of them showed Id1 protein tumor cell expression and
      50% displayed endothelial expression. In the metastatic patients group, lower
      levels of Id1 protein predicted a nonsignificant longer overall survival (13
      months vs. 7 months; P = .79). In the in silico analysis, however, lower levels
      of Id1 mRNA predicted a longer disease-free survival (61 months vs. not-reached;
      P = .018) and the hazard ratio for progression was 0.451 (P = .022) in favor of
      patients showing lower levels. CONCLUSION: In our cohort, it seems to be a
      differential epithelial expression of Id1 protein according to the prognostic
      features (metastatic/poor prognosis vs. organ-confined/good prognosis). In
      localized tumors treated with radical prostatectomy, higher Id1 mRNA expression
      levels might predict a higher hazard ratio for progression and a shorter disease
      free survival. Further validation of these results in larger prospective series
      is warranted.

PMID- 24129126
TI  - Evaluation of estrogenic activity in animal diets using in vitro assay.
AB  - A yeast estrogen bioassay (RIKILT REA) was in-house validated for feed on the
      5MUg 17beta-estradiol-equivalents per kg level according to EC Decision
      2002/657/EC. All the performance characteristics met the criteria as defined in
      the Decision and the REA is able to detect 17beta-estradiol in animal feed at a
      low level of 1.15-2MUgkg(-1). Subsequently, the developed and validated procedure
      was applied to determine the estrogenic activity in 24 feed samples intended for
      food producing animals, pets and laboratory animals. Two batches of rodent diet
      Murigran and one dog feed have been presented as a suspect, i.e. gave responses
      above the determined decision limit (CCalpha) and detection capability (CCbeta).
      In assessing the performance of the estrogenic activity in these diets evaluated
      by comparison with the 17beta-estradiol calibration curve, 17beta-estradiol
      equivalence levels of 7.07MUg EEQkg(-1) and 9.54MUg EEQkg(-1) in two batches of
      rodent diet and 5.3MUg EEQkg(-1) in dog feed have been established. The
      activities observed in the rodent feed could be explained by chemical analysis,
      revealing high amounts of genistein, daidzein and trace amounts of zearalenone.
      In addition, the estrogenic activity in one of rodent feed was above the
      established CCalpha, but below the CCbeta values established and all other
      samples showed no estrogenic activity with responses below the CCalpha value,
      which corresponds to levels below 2MUg EEQkg(-1). 

PMID- 24129127
TI  - Possible discontinuation of therapies in inflammatory rheumatic diseases - as
      with initiation of therapies, a shared decision between patient and
      rheumatologist.

PMID- 24129128
TI  - Can we discontinue synthetic disease-modifying anti-rheumatic drugs in rheumatoid
      arthritis?
AB  - OBJECTIVES: When rheumatoid arthritis (RA) patients have achieved sustained good
      clinical responses can their disease-modifying anti-rheumatic drugs (DMARDs) be
      reduced or discontinued? This review addresses this question by summarising the
      clinical evidence about DMARD withdrawal. It includes an assessment of predictive
      factors for sustained DMARD-free remissions. METHODS: We evaluated the evidence
      for discontinuing DMARDs in stable RA in both randomised controlled trials (RCTs)
      and observational studies. RESULTS: Six RCTs evaluated DMARD monotherapy
      withdrawal in 501 RA patients with good clinical responses. Flares occurred in
      43/248 (17%) patients who continued DMARD monotherapy and in 117/253 (46%)
      patients who discontinued DMARDs. Individuals in whom DMARDs were withdrawn were
      three times more likely to have flares. Restarting DMARDs post-flare was usually
      successful. Four RCTs evaluated step-down DMARD combinations in comparison to
      DMARD monotherapy. Patients achieved good clinical responses with combination
      DMARDs, which were maintained after treatment was tapered to DMARD monotherapy.
      Four observational studies of tapering or stopping DMARDs in patients with
      sustained low disease activity states provided supportive evidence for
      discontinuing DMARDs in some patients. Flares during drug-free remissions were
      predicted by rheumatoid factor and anti-citrullinated protein antibody status.
      CONCLUSIONS: Drug-free remission is achievable in some RA patients.
      Discontinuation of DMARDs after patients achieve sustained remissions results in
      flares in many patients, which can usually be reversed by restarting DMARDs. Step
      down DMARD combinations are effective and achieve sustained responses. Further
      research is required to establish predictors of drug-free remission; these will
      identify individuals most likely to benefit or experience disease flares after
      discontinuing DMARDs.

PMID- 24129129
TI  - The role of low-dose glucocorticoids for rheumatoid arthritis in the biologic
      era.
AB  - In rheumatoid arthritis (RA), low-dose glucocorticoid (GC) therapy has a well
      established effect on disease activity. Particularly in early RA, robust evidence
      demonstrates that GC treatment in association with standard disease-modifying
      anti-rheumatic drugs (DMARDs) is effective in inducing high remission rates,
      earlier and more persistently. Despite international recommendations that
      discourage long-term concomitant GC use, the majority of the clinical trials and
      observational registries on biologic agents include a high proportion (up to 80%)
      of patients in treatment with GC. From an analysis of the literature, a
      substantial lack of reliable information about the efficacy of GC in association
      with biologic agents emerges; in particular, the role of GC co-therapy in
      sustaining remission after biological therapy discontinuation remains to be
      clarified. Given the increasing prevalence of patients in sustained remission, a
      rational discontinuation strategy should include low-dose GCs in the experimental
      design to elucidate their role in inducing and maintaining biologic-free
      remission, for efficacy, safety and pharmacoeconomic considerations. 

PMID- 24129130
TI  - The BeSt way of withdrawing biologic agents.
AB  - OBJECTIVES: Treat-to-target strategies in the management of patients with
      rheumatoid arthritis (RA) involve intensifying medication as long as low disease
      activity or remission is not achieved. Our aim was to discuss reasons and
      opportunities for tapering and discontinuing medication when the target is
      achieved, in particular of biological agents. METHODS: Data from the Behandel
      Strategieen (BeSt) study are presented, a multicentre randomised clinical trial
      comparing 4 treatment strategies in patients with recent onset active RA (1987
      criteria): 1. Sequential monotherapy, 2. Step up to combination therapy (both
      starting with methotrexate (MTX) monotherapy), 3. Initial combination therapy
      with MTX, sulfasalazine and prednisone and 4. Initial combination therapy with
      MTX and infliximab. Treatment adjustments involving dose increases, drug changes
      or expansion to combination therapy occurred based on three-monthly calculations
      of the Disease Activity Score (DAS), with a target of <=2.4. If this was achieved
      for 2 consecutive evaluations, treatment was tapered (combinations to
      monotherapy, monotherapy to maintenance dose). Prednisone and infliximab (either
      as part of initial treatment or as delayed treatment after failure on earlier
      therapies in arms 1, 2 and -for infliximab- 3) were always tapered and
      discontinued before other drugs. The outcomes of discontinuation of infliximab
      are presented. RESULTS: 77/120 (64%) of patients who started initial infliximab
      were able to discontinue infliximab, whereas 27/109 (25%) of patients who started
      delayed infliximab in arms 1-3 could discontinue infliximab. Discontinuation was
      independent of previous dose increases in order to achieve low DAS. After
      discontinuation of infliximab, 16 of 27 patients (59%) in arms 1-3 and 34 of 77
      patients (44%) in arm 4 suffered a DAS flare >2.4 and had to restart treatment.
      Median time without infliximab treatment was 17 (IQR 3-47) months, and 29 of the
      61 patients (58%) who needed to restart had been at least 1 year without
      infliximab. Restarting infliximab resulted in DAS <=2.4 in all patients, and
      there was no progression of radiological damage. Presence of shared epitope,
      smoking, and a long treatment with infliximab were independent predictors of
      infliximab restart. CONCLUSIONS: Data on infliximab discontinuation in the BeSt
      study suggest that this possible in 1 in 4 patients, or more if infliximab was
      the initial treatment, who have had at least 6 consecutive months of low disease
      activity. While MTX is continued, about 50% of patients can permanently stop
      infliximab without radiological damage progression, the others regain low disease
      activity after restarting infliximab. Treat to target strategies using biologic
      agents should include strategies for discontinuation.

PMID- 24129131
TI  - The when and how of biologic agent withdrawal in rheumatoid arthritis: learning
      from large randomised controlled trials.
AB  - There has been great interest lately concerning the possibility that in the
      treatment of rheumatoid arthritis, biologic agents might be withdrawn for
      patients who achieve desirable targets, such as low disease activity or
      remission. While there are a number of reasons why such a treatment paradigm
      might be desirable, there is a paucity of relevant data at present to guide
      clinicians about embarking on such a treatment change. Data is starting to
      emerge, much of it from controlled trials, that can provide some guidance as to
      which patients might be the best candidates for such an approach. These data will
      provide answers to the key questions that remain concerning this important
      potential paradigm shift in the treatment of rheumatoid arthritis as well as
      other systemic inflammatory autoimmune diseases. 

PMID- 24129132
TI  - Discontinuation of biologics in patients with rheumatoid arthritis.
AB  - The use of early aggressive treatment combined with the availability of
      biological agents targeting pro-inflammatory cytokines such TNF and IL-6 has
      greatly advanced the treatment of rheumatoid arthritis (RA). Clinical remission
      is a realistic primary goal and its maintenance leads to stabilisation of
      structural deterioration and functional remission. With the achievement of
      sustained remission, discontinuation of biological agents has emerged as an
      important consideration, with subsequent reductions in medication-induced side
      effects and health costs. Evidence from studies suggests that MTX-naive, early RA
      patients can achieve sustained biologic-free remission with no functional or
      radiographic progression, after treatment with combination TNF inhibitors and
      MTX. For patients with long-standing RA and who have previous inadequate
      responses to MTX, the evidence for sustained biologic-free remission is less
      convincing. The discontinuation of TNF-inhibitors after sustained remission has
      been shown to be possible in some long-standing RA patients with inadequate
      response to MTX, particularly in Japanese patients. However, high flare rates and
      adverse long-term outcomes have been documented in other studies. For these
      patients a biologic dose-reduction regimen may be preferable. The combination of
      early treatment with TNF inhibitors and MTX plus tight control of inflammation
      provide the best chance of a biologic-free remission or at least the possibility
      of 'biologic treatment holidays'. 

PMID- 24129134
TI  - Remission and possible discontinuation of biological therapy in axial
      spondyloarthritis.
AB  - Remission has not been a major topic in ankylosing spondylitis (AS) in recent
      years but there is now increasing interest in analogy to rheumatoid arthritis
      (RA). RA and AS are chronic inflammatory diseases with more differences than
      similarities. New classification criteria for axial spondyloarthritis (axSpA)
      have recently added patients with so called non-radiographic axSpA to the
      spectrum, hereby including earlier disease stages without structural changes.
      Therapeutic strategies include non-steroidal anti-inflammatory agents (NSAIDs)
      and biologics, mainly anti-TNF agents. Both work rather well for signs and
      symptoms, and possibly also for structure modification. Discontinuation of anti
      TNF agents has been a major topic in RA in the last 2 years. In axSpA there has
      been less enthusiasm because early reports have been rather discouraging.
      However, no prospective controlled trials have been performed. This is a clear
      unmet need which should be addressed in future trials. 

PMID- 24129133
TI  - Use of data from multiple registries in studying biologic discontinuation:
      challenges and opportunities.
AB  - Many studies have been conducted concerning discontinuation of biologic disease
      modifying anti-rheumatic drugs (DMARD), but mainly in trial settings which result
      in limited generalisability. Registry studies can complement the current
      literature of biologic DMARD discontinuation by providing more generalisable
      information. However, it may be necessary to combine registries to increase power
      and provide more diverse patient populations. This increased power could provide
      us information about risk and benefits of discontinuing biologic DMARD in typical
      clinical practice. However, use of multiple registries is not without challenges.
      In this review, we discuss the challenges to combining data across multiple
      registries, focusing on biologic discontinuation as an example. Challenges
      include: 1) generalizability of each registry; 2) new versus prevalent users
      designs; 3) outcome definitions; 4) different health care systems; 5) different
      follow up intervals; and 6) data harmonisation. The first three apply to each
      registry, and the last three apply to combining multiple registries. This review
      describes these challenges, corresponding solutions, and potential future
      opportunities. 

PMID- 24129135
TI  - Withdrawal of biologic therapy in axial spondyloarthritis: the experience in
      early disease.
AB  - Tumour necrosis factor-alpha inhibitors (TNF-blockers) are recommended for the
      treatment of predominantly axial spondyloarthritis (SpA), after failure of non
      steroidal anti-inflammatory drugs (NSAIDs). TNF-blockers are very effective drugs
      and also show a sustained and stable long-term response in axial SpA. A few
      trials indicated that withdrawal of TNF-blockers in longstanding ankylosing
      spondylitis (AS) is not feasible. However, a recent trial in very early axial SpA
      suggests that reaching a state of biologic-free low disease activity may be a
      realistic goal in some patients. This review summarises the available data
      concerning withdrawal of biologic therapies in early axial SpA. 

PMID- 24129136
TI  - Withdrawal of biologic therapy in axial spondyloarthritis: the experience in
      established disease.
AB  - Treatment of patients suffering from active ankylosing spondylitis (AS) with
      TNFalpha blockers, has been shown to result in clinically significant improvement
      of signs and symptoms of the disease. Long-term extension studies with these
      agents have shown sustained clinical efficacy for up to 10 years in patients who
      continued treatment. However, only a few studies have examined whether reduction
      of dosage of discontinuation of anti-TNF therapy is possible. In daily clinical
      practice, prolongation of treatment intervals is frequently tried in patients who
      are in clinical remission for longer periods of time, but no data on the success
      of that are available. Discontinuation of treatment is usually needed in patients
      who want to become pregnant, and in patients with severe infections. This review
      summarises what is known on the topic of discontinuation of biologic treatment in
      patients with AS. 

PMID- 24129137
TI  - Withdrawal of medical therapies in axial spondyloarthritis: what would be the
      optimal trial design?
AB  - Remission or low disease activity is achievable in patients with axial
      spondyloarthritis (SpA), and remission has been defined as one of the main
      targets in treating patients with axial SpA. However, it is unclear what actions
      should be taken once remission has occurred. Very little data are available
      concerning the effect of TNF inhibitors (TNFi) dosage adjustment or on withdrawal
      strategies in patients with axial SpA and/or in patients with ankylosing
      spondylitis (AS). Most issues relating to withdrawal of treatment in patients who
      are in remission cannot be addressed with traditional randomised placebo
      controlled trials (RCT). Facing these challenges, there is a need for conducting
      trials with an innovative trial design to reflect real-life practice. Possible
      strategies upon remission include continuation, dose reduction or withdrawal of
      the effective therapy. Future scenarios should recognise heterogeneity in
      patients with axial SpA, which makes it questionable whether different trial
      designs will be applicable for the whole group of axial SpA. Several questions
      should be addressed before conducting a trial to study remission in patients with
      axial SpA: definition of remission (clinical and/or imaging remission), duration
      of remission as a defining inclusion criterion, predictors of remission,
      definition of subgroups (e.g. TNFi naive patients or patients who will most
      likely remain in remission), when to restart and finally dose-adjustment after
      restart of the therapy. 

PMID- 24129138
TI  - Can biologic therapies be withdrawn or tapered in psoriatic arthritis?
AB  - There is a paucity of data on tapering and withdrawing therapy in psoriatic
      arthritis but advances in treatment and outcome measures suggest it is now time
      to be looking more closely at this. Several highly effective therapies are
      available providing the opportunity to achieve low disease activity. However,
      these therapies are associated with a marked increase in direct costs and
      patients are exposed to potentially life threatening adverse events. In addition
      to effective therapies the science of outcome assessment means that there are now
      suitable validated criteria for low disease activity which will allow both treat
      to-target and a suitable measure of continuing low disease. Given these
      conditions, suitably designed randomized controlled trials of treatment
      withdrawal are now needed. Such studies will allow us to determine disease
      characteristics predictive of flare upon treatment withdrawal. In this way
      identifying which patients can successfully stop therapy will allow a more
      personalized approach to treatment decisions in PsA and will minimise risks and
      costs associated with ongoing therapy. 

PMID- 24129139
TI  - Can traditional disease-modifying anti-rheumatic drugs be withdrawn or tapered in
      psoriatic arthritis?
AB  - Psoriatic arthritis (PsA) is a complex, multisystem disease with musculoskeletal
      and skin manifestations frequently associated with features of the metabolic
      syndrome. For many years, treatment strategies were largely borrowed from the
      rheumatoid arthritis literature, with clinical trials of traditional DMARDs in
      PsA often inadequate and using limited outcome measures. Nonetheless, DMARDs - in
      particular, methotrexate - remain the treatment of first choice for most
      rheumatologists treating this disease, especially for those with prominent
      polyarticular involvement. While there is no agreed definition of remission in
      PsA, a number of longitudinal studies suggests that remission can be achieved in
      approximately 25% of patients treated with traditional DMARDs, with drug-free
      remission possible in <10%. There are many unanswered questions, and this review
      concludes by highlighting a research agenda which aims to address some of the
      most critical questions for physicians and patients alike faced with deciding if
      treatment should be withdrawn or continued when disease remission is achieved. 

PMID- 24129140
TI  - Is reduction or discontinuation of therapy an acceptable possibility in psoriatic
      arthritis?
AB  - Remission in psoriatic arthritis (PsA), albeit variably defined, is a desirable
      and achievable state, especially in the era of biologic therapy. Historically,
      studies have used remission criteria derived from rheumatoid arthritis (RA),
      which indicate that remission is seen in a greater percentage of patients than in
      RA, including the possibility of drug-free remission in some patients. The
      Minimal Disease Activity (MDA) measure developed by the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is a currently
      acceptable goal of therapy, taking into account PsA-specific elements such as
      skin disease and enthesitis. Newer PsA composite measures which include
      thresholds for remission are under development and are now included in
      prospective clinical trials. Once remission is achieved and sustained on therapy,
      a natural question is whether treatment can be reduced or discontinued to avoid
      treatment toxicities and costs. Exploratory data are being analysed from
      observational cohorts regarding the capacity to reduce treatment dose, dose
      frequency, or discontinue use of a medication whilst maintaining remission. A
      controlled dose-reduction and discontinuation study design is outlined, which may
      provide controlled evidence for such a paradigm of treatment. 

PMID- 24129141
TI  - Continuous versus intermittent therapy for moderate-to-severe psoriasis.
AB  - Psoriasis is a chronic immune-mediated inflammatory disease of unknown etiology.
      Unlike other chronic inflammatory diseases receiving continuous treatment,
      psoriasis has traditionally been treated intermittently secondary to concern for
      cumulative toxicity of conventional systemic therapies. However, the development
      of targeted anti-inflammatory biologic agents allowed for continuous therapy for
      most patients. Herein, we review the literature for intermittent versus
      continuous use of widely available therapies for moderate-to-severe psoriasis:
      phototherapy, topical corticosteroids, conventional systemic therapies and
      biologic agents. These data support continuous treatment in biologic therapy,
      such as etanercept, adalimumab, infliximab, and ustekinumab. Intermittent therapy
      with biologic agents leads to decreased efficacy and sometimes increased side
      effects. When conventional systemic therapy is used continuously, it is more
      efficacious; however the data support intermittent use of methotrexate and
      cyclosporine due to cumulative toxicities. Psoriasis severity may wax and wane,
      but it is a chronic disease requiring continuous treatment for optimal control of
      inflammatory activity and to minimise cutaneous involvement. 

PMID- 24129142
TI  - Withdrawal of therapy in non-renal systemic lupus erythematosus: is this an
      achievable goal?
AB  - Survival of patients with systemic lupus erythematosus (SLE) has greatly improved
      over the decades. Many reasons for treatment withdrawal may be faced by the
      physician during the disease course, such as inactivity of disease, damage
      accrual, risks of long-term side effects, or potential interactions with other
      drugs required to treat concomitant conditions, as well as patients' preferences.
      Therefore, analysis of long-term therapy and treatment withdrawal is important.
      We have examined the available literature concerning withdrawal of therapy, with
      attention to glucocorticoids, antimalarial drugs and traditional
      immunosuppressive drugs in SLE patients who did not have renal disease. We
      expanded our search to address two questions: i) advantages of long-term therapy
      in SLE (i.e. reduction of flares, reduction of damage accrual, improved
      survival); and (ii) burden/side effects of therapy in SLE. Studies are needed to:
      i) define remission in SLE; ii) define the advantages of long-term therapy in non
      renal lupus in terms of prevention of flares; iii) clarify the risks related with
      long-term immunosuppressive therapy; iv) identify the appropriate patient at the
      appropriate time for withdrawal of corticosteroids or immunosuppressive therapy;
      and v) define withdrawal/tapering strategies. 

PMID- 24129143
TI  - What happens after complete withdrawal of therapy in patients with lupus
      nephritis.
AB  - OBJECTIVES: Whether and when is it possible to completely stop immunosuppression
      in patients with lupus nephritis is still poorly defined. METHODS: An attempt to
      slowly and progressively eliminate steroids and immunosuppressive drugs was tried
      in 73 of 161 (45.3%) patients with lupus nephritis who achieved a stable clinical
      remission defined as normal serum creatinine, proteinuria <0.5g/24h, inactive
      urine sediment, and no clinical signs of extra-renal activity of SLE for at least
      12 months. RESULTS: Twenty-one out of the 73 patients (28.7%) who met the
      criteria for withdrawal of treatment developed flares during the phase of
      progressive reduction of therapy and their treatment was reinforced. Twenty
      patients entered remission again; the last patient was lost to follow-up at
      achievement of partial remission. In the other 52 of the 73 patients (71.2%), it
      was possible to completely withdraw treatment. Of these, 32 patients (group A)
      did not resume therapy for the subsequent follow-up (median 101.8 months); the
      other 20 patients (group B) had at least one flare, in median 37 months after
      withdrawing therapy, and had to be retreated. At the last observation, after a
      median follow-up of 286 months, 10 of these 20 patients were off therapy. At the
      last observation, two patients in group A and two in group B had died, no patient
      of group A and two of group B had developed renal insufficiency (serum creatinine
      2.5 and 3 mg/dl, respectively). Compared to patients in group B, group A patients
      received longer treatment (98.1 vs. 31.0 months; p=0.01), had longer remission
      (52.8 vs. 12.0 months; p=0.000) before withdrawal of therapy, and continued
      chloroquine after stopping therapy (52% vs. 10%; p=0.004). In comparison to
      patients who never stopped therapy, patients who were able to interrupt treatment
      had lower risk of chronic renal insufficiency (3.8% vs. 28.4%; p=0.000), end
      stage renal disease (0 vs. 12.8%; p=0.01), arterial hypertension (32.7% vs.
      66.9%; p=0.000) and cardiovascular events (11.5% vs. 27.5%; p=0.04). CONCLUSIONS:
      Complete withdrawal of therapy is feasible in selected patients who achieved
      stable remission after long-term treatment. The reduction of treatment must be
      done in a very gradual manner, progressively and under strict medical
      surveillance. The withdrawal of therapy allows the patients to reduce renal and
      extra-renal damage accrual. Treatment with chloroquine may help to maintain
      remission in patients who discontinue steroids and immunosuppressive drugs.

PMID- 24129144
TI  - New drugs in systemic lupus erythematosus: when to start and when to stop.
AB  - Survival of patients with systemic lupus erythematosus (SLE) has greatly improved
      compared to earlier decades. However, this improvement appears to have reached a
      plateau. In addition, damage accrual appears to have an important impact on
      patient prognosis. In this scenario a number of new drugs targeting different
      pathways of the immune response are being developed, and some are already
      available in clinical practice. In clinical practice and in clinical trials, the
      indications for treating SLE patients with new drugs are active or refractory
      disease despite standard-of-care treatment. While RCTs are able to document the
      capacity of new drugs to control the disease in selected patients, many important
      questions arise from clinical practice and at present are largely unanswered.
      When should we start a new drug? Should this drug be introduced early, as are
      anti-TNF drugs in rheumatoid arthritis? Perhaps some drugs should be initiated
      only after a patient's incomplete response? How many traditional drugs should be
      used and for how long, before considering a new therapy? Should we stop an
      effective drug and if yes, when and how? Additional studies and data derived from
      registries and observational studies will give valuable evidence to answer these
      questions. In this article, we review indications for the use of new drugs in
      SLE, and examine existing data on patient outcome after withdrawal, focusing our
      attention on rituximab and belimumab. 

PMID- 24129146
TI  - Discontinuation of therapies in vasculitis.
AB  - For most patients with vasculitis, treatment will result in prevention of
      mortality and also lead to clinical remission. This increased survival is of
      course most welcome, but the burden of surviving an episode of acute vasculitis
      consists of the effects of the disease as well as the adverse events from
      treatment. Therefore, we have begun to explore the possibility of withdrawing
      treatment in order to avoid long-term medication toxicities. Whilst this will
      reduce short-term side effects, if withdrawal leads to subsequent uncontrolled
      flares of disease, the need for additional therapy may outweigh any benefit from
      a drug-free holiday. For very mild forms of vasculitis, such as isolated skin
      vasculitis, the best option may be to avoid treatment altogether. In those
      patients with vasculitis secondary to an identifiable agent such as drug toxicity
      or an infectious organism, discontinuing the offending drug or treating the
      infection will usually resolve or cure the vasculitis. In patients with localised
      vasculitis, surgical removal of the affected area can be curative. Other forms of
      vasculitis have a self-limited duration, after which there does not appear to be
      any clinical evidence of disease, such as is the case for the majority of
      patients with giant cell arteritis. By contrast, in many forms of vasculitis,
      especially those associated with the presence of anti-neutrophil cytoplasm
      antibody (ANCA), relapse occurs in at least half the patients. Where
      glucocorticoid therapy is used for any length of time, in doses of >5 mg/day,
      side effects are almost universal. Adding a concomitant agent in the attempt to
      shorten the course and/or reduce the dose of glucocorticoid treatment may be
      effective, but can also result in toxicity from the alternative agent, and leaves
      the patient on immunosuppressive therapy. More toxic therapy, such as
      cyclophosphamide, usually is administered only for a limited time or cumulative
      amount, in order to achieve induction of remission or flare in severe disease.
      The advent of targeted biologic therapy offers the opportunity to provide more
      effective, less toxic and perhaps more long-lasting control of disease. Rituximab
      in small-vessel vasculitis can result in long-lasting control of disease, for 18
      months or more, from a single course of treatment. Suppression of the interleukin
      6 pathway may be effective in large-vessel vasculitis. Unfortunately, none of
      these therapies is capable of 'cure' for the majority of patients. Therefore,
      discontinuation of therapy remains unachievable for most patients with
      vasculitis, at least in the first few years of disease. Short courses of
      intensive, aggressive therapy are followed by the use of maintenance treatment.
      Long-term follow-up studies are required to determine the potential benefit of
      early, more effective control of vasculitis. 

PMID- 24129145
TI  - Discontinuation of therapies in polymyalgia rheumatica and giant cell arteritis.
AB  - Glucocorticoids are highly effective in treating polymyalgia rheumatica and giant
      cell arteritis, but their use is associated with numerous adverse events.
      Therefore, it is important to use them for the shortest period of time possible.
      The published evidence suggests that discontinuation of GC is feasible in a
      substantial number of patients with polymyalgia rheumatica and giant cell
      arteritis after an adequate period of treatment, provided that glucocorticoids
      are tapered gradually. Recurrences are relatively infrequent in polymyalgia
      rheumatica and somewhat more common in giant cell arteritis. Immunosuppressive
      agents may be used in patients with frequently relapsing or recurring disease to
      decrease exposure to glucocorticoids. 

PMID- 24129147
TI  - Possible discontinuation of therapies after clinical remission in juvenile
      idiopathic arthritis.
AB  - Several studies have examined effects of discontinuing treatment after clinical
      remission in children with JIA. So far, only methotrexate and tumour necrosis
      factor alpha (TNF) inhibitors have been investigated. Overall, the relapse rate
      after termination of these medications was substantial. However, with the
      exception of one controlled trial of methotrexate, all analyses are
      retrospective. In addition, the results obtained for TNF-alpha inhibitors are
      variable and conclusions of existing studies are often divergent. No consistent
      predictors of the risk of flare were identified. Some evidence exists that low
      doses of medications may be sufficient to maintain remission. Because achievement
      of inactive disease has become increasingly more common in paediatric
      rheumatology practice, evidence-based data and expert recommendations to guide
      drug discontinuation are needed. This information should help to avoid both the
      risks and costs of prolonged therapy and to minimize the likelihood of disease
      flares. It should also be clarified whether it is more advantageous to stop
      treatment abruptly or to taper it gradually by reducing the dosage progressively
      or by increasing the interval between doses. Another key objective for future
      studies is to identify predictors of disease flare after treatment
      discontinuation. In addition, the optimal policy for discontinuation of other
      biologic medications used in children with JIA, such as anakinra, abatacept,
      tocilizumab, and canakinumab, should be established. 

PMID- 24129150
TI  - Effects of Escherichia coli- and Staphylococcus aureus-induced mastitis in
      lactating cows on oocyte developmental competence.
AB  - Mastitis is associated with decreased fertility in dairy cows. In the current
      study, we created an experimental model to simulate short-term mastitis by a
      single intramammary administration of Gram-negative endotoxin of Escherichia coli
      origin (G-), or Gram-positive toxin of Staphylococcus aureus origin (G+), to
      examine the effect of mastitis on oocyte developmental competence. Healthy
      Holstein cows were synchronized, and follicular fluid (FF) of cows treated with
      G+ or G- and of uninfected cows (controls) was aspirated from the preovulatory
      follicles by transvaginal ultrasound procedure. The aspirated FF was used as
      maturation medium for in vitro embryo production. The distribution of matured
      oocytes into different cortical granule classes and meiotic stages was affected
      by G- administration (P<0.05) but not by G+ administration. The proportion of
      oocytes that cleaved to two- and four-cell stage embryos (44 h postfertilization)
      was lower in both G+ and G- groups than in controls (P<0.05). Blastocyst
      formation rate (7-8 days postfertilization) was lower in the G- group (P<0.05)
      and numerically lower in the G+ group compared with their uninfected
      counterparts. The total cell number in blastocysts did not differ among groups;
      however, the apoptotic index was higher in the G+ group (P<0.05), but not in the
      G- group, relative to controls. Examining mRNA relative abundance in oocytes and
      early embryos revealed mastitis-induced alterations in PTGS2 (COX2), POU5F1, and
      HSF1 but not in SLC2A1 (GLUT1) or GDF9. Results indicate a differential
      disruptive effect of mastitis induced by G- and G+ on oocyte developmental
      competence in association with alterations in maternal gene expression.

PMID- 24129151
TI  - The evolution of viviparity: molecular and genomic data from squamate reptiles
      advance understanding of live birth in amniotes.
AB  - Squamate reptiles (lizards and snakes) are an ideal model system for testing
      hypotheses regarding the evolution of viviparity (live birth) in amniote
      vertebrates. Viviparity has evolved over 100 times in squamates, resulting in
      major changes in reproductive physiology. At a minimum, all viviparous squamates
      exhibit placentae formed by the appositions of maternal and embryonic tissues,
      which are homologous in origin with the tissues that form the placenta in therian
      mammals. These placentae facilitate adhesion of the conceptus to the uterus as
      well as exchange of oxygen, carbon dioxide, water, sodium, and calcium. However,
      most viviparous squamates continue to rely on yolk for nearly all of their
      organic nutrition. In contrast, some species, which rely on the placenta for at
      least a portion of organic nutrition, exhibit complex placental specializations
      associated with the transport of amino acids and fatty acids. Some viviparous
      squamates also exhibit reduced immunocompetence during pregnancy, which could be
      the result of immunosuppression to protect developing embryos. Recent molecular
      studies using both candidate-gene and next-generation sequencing approaches have
      suggested that at least some of the genes and gene families underlying these
      phenomena play similar roles in the uterus and placenta of viviparous mammals and
      squamates. Therefore, studies of the evolution of viviparity in squamates should
      inform hypotheses of the evolution of viviparity in all amniotes, including
      mammals. 

PMID- 24129152
TI  - Wt1 deficiency causes undifferentiated spermatogonia accumulation and meiotic
      progression disruption in neonatal mice.
AB  - Spermatogenesis is a complex process involving the regulation of multiple cell
      types. As the only somatic cell type in the seminiferous tubules, Sertoli cells
      are essential for spermatogenesis throughout the spermatogenic cycle. The Wilms
      tumor gene, Wt1, is specifically expressed in the Sertoli cells of the mouse
      testes. In this study, we demonstrated that Wt1 is required for germ cell
      differentiation in the developing mouse testes. At 10 days post partum, Wt1
      deficient testes exhibited clear meiotic arrest and undifferentiated
      spermatogonia accumulation in the seminiferous tubules. In addition, the
      expression of claudin11, a marker and indispensable component of Sertoli cell
      integrity, was impaired in Wt1(-/flox); Cre-ER(TM) testes. This observation was
      confirmed in in vitro testis cultures. However, the basal membrane of the
      seminiferous tubules in Wt1-deficient testes was not affected. Based on these
      findings, we propose that Sertoli cells' status is affected in Wt1-deficient
      mice, resulting in spermatogenesis failure. 

PMID- 24129153
TI  - Generation of neural progenitors from induced Bama miniature pig pluripotent
      cells.
AB  - Pig pluripotent cells may represent an advantageous experimental tool for
      developing therapeutic application in the human biomedical field. However, it has
      previously been proven to be difficult to establish from the early embryo and its
      pluripotency has not been distinctly documented. In recent years, induced
      pluripotent stem (iPS) cell technology provides a new method of reprogramming
      somatic cells to pluripotent state. The generation of iPS cells together with or
      without certain small molecules has become a routine technique. However, the
      generation of iPS cells from pig embryonic tissues using viral infections
      together with small molecules has not been reported. Here, we reported the
      generation of induced pig pluripotent cells (iPPCs) using the iPS technology in
      combination with valproic acid (VPA). VPA treatment significantly increased the
      expression of pluripotent genes and played an important role in early
      reprogramming. We showed that iPPCs resembled pig epiblast cells in their
      morphology and pluripotent markers, such as OCT4, NANOG, and SSEA1. It had a
      normal karyotype and could form embryoid bodies, which express three germ layer
      markers in vitro. In addition, the iPPCs might directly differentiate into neural
      progenitors after being induced with the retinoic acid and extracellular matrix.
      Our study established a reasonable method to generate pig pluripotent cells,
      which might be a new donor cell source for human neural disease therapy. 

PMID- 24129154
TI  - Comparison of fecundity and offspring immunity in zebrafish fed Lactobacillus
      rhamnosus CICC 6141 and Lactobacillus casei BL23.
AB  - To increase the knowledge of probiotic effects on zebrafish (Danio rerio), we
      compare the effects of two probiotic strains, Lactobacillus rhamnosus CICC 6141
      (a highly adhesive strain) and Lactobacillus casei BL23 (a weakly adhesive
      strain), on zebrafish reproduction and their offsprings' innate level of immunity
      to water-borne pathogens. During probiotics treatments from 7 to 28 days, both
      the Lactobacillus strains, and especially L. casei BL23, significantly increased
      fecundity in zebrafish: higher rates of egg ovulation, fertilization, and
      hatching were observed. Increased densities of both small and large vitellogenic
      follicles, seen in specimens fed either Lactobacillus strain, demonstrated
      accelerated oocyte maturation. Feeding either strain of Lactobacillus upregulated
      gene expression of leptin, kiss2, gnrh3, fsh, lh, lhcgr, and paqr8, which were
      regarded to enhance fecundity and encourage oocyte maturation. Concomitantly, the
      gene expression of bmp15 and tgfb1 was inhibited, which code for local factors
      that prevent oocyte maturation. The beneficial effects of the Lactobacillus
      strains on fecundity diminished after feeding of the probiotics was discontinued,
      even for the highly adhesive gut Lactobacillus strain. Administering L. rhamnosus
      CICC 6141 for 28 days was found to affect the innate immunity of offspring
      derived from their parents, as evinced by a lower level of alkaline phosphatase
      activity in early larval stages. This study highlights the effects of probiotics
      both upon the reproductive process and upon the offsprings' immunity during early
      developmental stages. 

PMID- 24129155
TI  - Anti-listeria activity of poly(lactic acid)/sawdust particle biocomposite film
      impregnated with pediocin PA-1/AcH and its use in raw sliced pork.
AB  - A novel poly(lactic acid) (PLA)/sawdust particle (SP) biocomposite film with anti
      listeria activity was developed by incorporation of pediocin PA-1/AcH (Ped) using
      diffusion coating method. Sawdust particle played an important role in embedding
      pediocin into the hydrophobic PLA film. The anti-listeria activity of the PLA/SP
      biocomposite film incorporated with Ped (PLA/SP+Ped) was detected, while no
      activity against the tested pathogen was observed for the control PLA films
      (without SP and/or Ped). Dry-heat treatment of film before coating with Ped
      resulted in the highest Ped adsorption (11.63 +/- 3.07 MUg protein/cm(2)) and the
      highest anti-listeria activity. A model study of PLA/SP+Ped as a food-contact
      antimicrobial packaging on raw sliced pork suggests a potential inhibition of
      Listeria monocytogenes (99% of total listerial population) on raw sliced pork
      during the chilled storage. This study supports the feasibility of using
      PLA/SP+Ped film to reduce the initial load of L. monocytogenes on the surface of
      raw pork.

PMID- 24129156
TI  - Toxin producing Bacillus cereus persist in ready-to-reheat spaghetti Bolognese
      mainly in vegetative state.
AB  - The potential of Bacillus cereus to cause a diarrheal toxico-infection is related
      to its ability to perform de novo enterotoxin production in the small intestine.
      A prerequisite for this is presence of sufficient numbers of B. cereus that have
      survived gastro-intestinal passage. It is known that the percentage of survival
      is much smaller for vegetative cells in comparison to spores and it is therefore
      important to know the state in which B. cereus is ingested. The results of the
      current study performed on twelve B. cereus strains, comprising both diarrheal
      and emetic type, indicate that exposure via contaminated foods mainly concerns
      vegetative cells. Inoculated vegetative cells grew to high counts, with the
      growth dynamic depending on the storage temperature. At 28  degrees C growth to
      high counts resulted in spore formation, in general, after 1 day of storage. One
      strain was an exception, producing spores only after 16 days. At 12  degrees C
      obtained high counts did not result in spore formation for 11 of 12 tested
      strains after two weeks of storage. The highest counts and time to sporulation
      were different between strains, but no difference was observed on the group level
      of diarrheal and emetic strains. The spore counts were always lower than
      vegetative cell counts and occurred only when food was obviously sensory spoiled
      (visual and odor evaluation). Similar observations were made with food inoculated
      with B. cereus spores instead of vegetative cells. Although the prospect of
      consuming spores was found very weak, the numbers of vegetative B. cereus cells
      were high enough, without obvious sensory deviation, to survive in sufficient
      level to cause diarrheal toxico-infection.

PMID- 24129157
TI  - Journal policy on research funded by the tobacco industry.

PMID- 24129158
TI  - Response to: an approach to 'use of split thickness plantar skin grafts in the
      treatment of hyperpigmented skin-grafted fingers and palms in previously burned
      patients'.

PMID- 24129159
TI  - Epidemiology of paediatric burns in Lithuania: focus on a vulnerable population
      exposed to the risk of scalds at home without hot tap water supply.
AB  - OBJECTIVE: To describe the epidemiology of paediatric burns in Lithuania,
      identify the trends of burn occurrence, the vulnerable population and aetiology.
      METHODS: This study was based on all inclusive national information obtained from
      the National Health Insurance database for the period of 2001-2010. Information
      on the burns aetiology was collected in the Hospital of Lithuanian University of
      Heath Sciences Kauno Klinikos. FINDINGS: 7146 children in the age group of 0-14
      were hospitalized in Lithuania and constituted 44% of all admissions due to
      burns. The incidence among boys was 149.8 and among girls 99.9 per 100,000. The
      highest risk of burns was observed from 11 to 15 months of age. Scalding in 0-1
      years age group composed 96% of all burns in this age group. CONCLUSION: Children
      younger than 2 years of age are a vulnerable population of burns in Lithuania.
      Scalding was main cause of their burns. The aetiological subgroups of scalding
      were scalding with hot drinks/food and scalding with hot water meant for
      household. The major part of scalding with hot drinks was due to scalding with
      parents' drinks. Scalding with hot water meant for household is associated with
      the lack of hot water supply.

PMID- 24129161
TI  - IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and
      colitis in mice.
AB  - T helper type 17 (Th17) cells have been implicated in autoimmunity and
      inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived
      cytokines such as interleukin (IL)-1beta and IL-6 are key mediators supporting
      Th17 differentiation, yet how these factors are induced in vivo remains unclear.
      Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1beta production and
      Th17 differentiation. IL-27Ralpha-/- T-cell receptor (TCR)beta-/- recipients fail
      to develop gut inflammation following naive CD4 T-cell transfer, whereas IL
      27Ralpha+/+ TCRbeta-/- recipients develop severe colitis. Investigation of T-cell
      responses exhibits that IL-27Ralpha-/- TCRbeta-/- mice do not support Th17
      differentiation with significantly decreased levels of IL-6 and IL-1beta by APCs.
      Our study has identified a novel proinflammatory role for IL-27 in vivo that
      promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs. 

PMID- 24129160
TI  - Dectin-2 sensing of house dust mite is critical for the initiation of airway
      inflammation.
AB  - How the immune system senses aeroallergens and triggers an aberrant inflammation
      is poorly understood. Dectin-2 is a house dust mite (HDM)-sensing pattern
      recognition receptor. In a 3-week mouse model of repeated intranasal HDM
      challenge, anti-Dectin-2 potently attenuated the characteristic allergic
      inflammation and airway hyper-responsiveness. Anti-Dectin-2 also prevented
      neutrophil influx following a single HDM challenge. Interestingly, cysteinyl
      leukotrienes, but not chemokine and cytokine levels were inhibited by anti-Dectin
      2 in this acute model, and in ex vivo challenge of cultured alveolar macrophages
      with HDM. Furthermore in the single-challenge model, zileuton, an inhibitor of
      leukotriene production, produced a similar effect as Dectin-2 blockade. Together
      these data suggest alveolar macrophage sensing of HDM by Dectin-2 elicits the
      production of cysteinyl leukotrienes, and this axis is key for the initiation of
      airway inflammation to this aeroallergen. Finally, we found Dectin-2-positive
      infiltrating cells present in bronchial biopsies from asthmatic subjects. 

PMID- 24129162
TI  - TNFalpha-dependent development of lymphoid tissue in the absence of RORgammat+
      lymphoid tissue inducer cells.
AB  - Lymphoid tissue often forms within sites of chronic inflammation. Here we report
      that expression of the proinflammatory cytokine tumor necrosis factor alpha
      (TNFalpha) drives development of lymphoid tissue in the intestine. Formation of
      this ectopic lymphoid tissue was not dependent on the presence of canonical
      RORgt(+) lymphoid tissue-inducer (LTi) cells, because animals expressing
      increased levels of TNFalpha but lacking RORgt(+) LTi cells (TNF/Rorc(gt)(-/-)
      mice) developed lymphoid tissue in inflamed areas. Unexpectedly, such animals
      developed several lymph nodes (LNs) that were structurally and functionally
      similar to those of wild-type animals. TNFalpha production by F4/80(+) myeloid
      cells present within the anlagen was important for the activation of stromal
      cells during the late stages of embryogenesis and for the activation of an
      organogenic program that allowed the development of LNs. Our results show that
      lymphoid tissue organogenesis can occur in the absence of LTi cells and suggest
      that interactions between TNFalpha-expressing myeloid cells and stromal cells
      have an important role in secondary lymphoid organ formation. 

PMID- 24129163
TI  - Pro-inflammatory effects of matrix metalloproteinase 7 in acute inflammation.
AB  - Matrix metalloproteinase 7 (MMP7) is a member of the MMP family. In the small
      intestine, MMP7 is responsible for activating alpha-defensins, which are broad
      spectrum anti-microbial peptides produced by the Paneth cells. We report that
      MMP7(-/-) mice are resistant to LPS-induced lethality and that this resistance is
      correlated with reduced levels of systemic cytokines. LPS induced the
      upregulation and activation of MMP7 in the small intestine, degranulation of the
      Paneth cells, and induction of intestinal permeability in MMP7(+/+) mice. In
      MMP7(-/-) mice, both LPS-induced intestinal permeability and consequent bacterial
      translocation to the mesenteric lymph nodes were reduced. Based on gene
      expression analysis and evaluation of intestinal damage, we attribute the
      protected state of MMP7(-/-) mice to reduced intestinal inflammation.
      Interestingly, we found that different alpha-defensins, namely Crp1 (DEFA1) and
      Crp4 (DEFA4), can stimulate IL-6 release in macrophages and ileum explants in a
      TLR4 independent way. We conclude that absence of MMP7 protects mice from LPS
      induced intestinal permeability and lethality, and suggest that MMP7-activated
      alpha-defensins, in addition to their previously recognized bactericidal and anti
      inflammatory roles, may exhibit pro-inflammatory activities in the intestine by
      activating macrophages and amplifying the local inflammatory response in the gut,
      leading to intestinal leakage and subsequent increase in systemic inflammation. 

PMID- 24129164
TI  - CX3CR1+ cells facilitate the activation of CD4 T cells in the colonic lamina
      propria during antigen-driven colitis.
AB  - Dendritic cells (DCs) and macrophages populate the intestinal lamina propria to
      initiate immune responses required for the maintenance of intestinal homeostasis.
      To investigate whether CX3CR1(+) phagocytes communicate with CD4 T cells during
      the development of transfer colitis, we established an antigen-driven colitis
      model induced by the adoptive transfer of DsRed OT-II cells in CX3CR1(GFP/+) *
      RAG(-/-) recipients challenged with Escherichia coli expressing ovalbumin (OVA)
      fused to a cyan fluorescent protein (CFP). After colonization of CX3CR1(GFP/+) *
      RAG(-/-) animals with red fluorescent E. coli pCherry-OVA, colonic CX3CR1(+)
      cells but not CD103(+) DCs phagocytosed E. coli pCherry-OVA. Degraded bacterial
      derived antigens are transported by CD103(+) DCs to mesenteric lymph nodes
      (MLNs), where CD103(+) DCs prime naive T cells. In RAG(-/-) recipients
      reconstituted with OT II cells and gavaged with OVA-expressing E. coli, colonic
      CX3CR1(+) phagocytes are in close contact with CD4 T cells and presented
      bacterial-derived antigens to CD4 T cells to activate and expand effector T
      cells. 

PMID- 24129166
TI  - Gene therapy as a new treatment option for inherited monogenic diseases.
AB  - BACKGROUND: Gene therapy, replacing a defective gene by a functional copy, has
      been in development for more than 40years. Initial efforts involved engineering
      viral vectors to deliver genes to the appropriate cells. Early successes in
      severe combined immunodeficiency (SCID) were later derailed by safety issues
      including host reaction to the vector and gene insertion near promoters that
      favored secondary leukemia. METHODS: Systematic review of the literature using
      PubMed.gov with key word gene therapy from 1972 to March 2013. Google search with
      key word gene therapy. RESULTS: Despite early setbacks, progresses for monogenic
      diseases continued unabated. Patients with SCIDs have been cured and the first
      gene therapy has been approved for lipoprotein lipase deficiency. Many clinical
      research studies are ongoing as part of systematic clinical development program
      with a view to have more gene therapies approved. CONCLUSION: Our review
      highlights progresses and questions that remain to be answered to make gene
      therapy an integral part of our therapeutic arsenal.

PMID- 24129165
TI  - Aluminum enhances inflammation and decreases mucosal healing in experimental
      colitis in mice.
AB  - The increasing incidence of inflammatory bowel diseases (IBDs) in developing
      countries has highlighted the critical role of environmental pollutants as
      causative factors in their pathophysiology. Despite its ubiquity and immune
      toxicity, the impact of aluminum in the gut is not known. This study aimed to
      evaluate the effects of environmentally relevant intoxication with aluminum in
      murine models of colitis and to explore the underlying mechanisms. Oral
      administration of aluminum worsened intestinal inflammation in mice with 2,4,6
      trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and
      chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased
      the intensity and duration of macroscopic and histologic inflammation, colonic
      myeloperoxidase activity, inflammatory cytokines expression, and decreased the
      epithelial cell renewal compared with control animals. Under basal conditions,
      aluminum impaired intestinal barrier function. In vitro, aluminum induced
      granuloma formation and synergized with lipopolysaccharide to stimulate
      inflammatory cytokines expression by epithelial cells. Deleterious effects of
      aluminum on intestinal inflammation and mucosal repair strongly suggest that
      aluminum might be an environmental IBD risk factor. 

PMID- 24129167
TI  - Simvastatin versus triptorelin in prevention of pain recurrences after surgery
      for endometriosis.

PMID- 24129168
TI  - Effects of smokeless tobacco (Maras powder) use on carotid intima media
      thickness.
AB  - BACKGROUND: The aim of this study was to investigate the effects of smokeless
      tobacco (Maras powder, Nicotiana rustica Linn) on carotid intima media thickness.
      MATERIAL/METHODS: The study included 32 Maras powder users presenting to our
      Family Medicine outpatient clinic and 30 non-users of Maras powder as a control
      group. Carotid intima media thickness was measured by duplex ultrasonography.
      RESULTS: The mean age of the Maras powder users was 45.4+/-11.3 years and the
      mean age of the control group was 46.3+11.6 years. All the participants were
      male. The mean duration of Maras powder use was 27.3+/-11.6 years. Carotid intima
      media thickness was 0.73+/-0.20 mm in the Maras powder users and 0.49+/-0.14 mm
      in the controls. It was significantly higher in the Maras powder users (p<0.001).
      Blood pressure measured before Maras powder use in Maras powder users was similar
      to that measured in the control group (p>0.05). Systolic blood pressure and
      diastolic blood pressure values were also similar between MP users before using
      Maras powder and controls (p>0.05). Systolic blood pressures were 136.6+/-12.4
      mmHg and 109.7+/-9.7 mmHg after 30-60 minutes using Maras powder in the Maras
      powder users and in the controls, respectively. Diastolic blood pressures were
      87.2+/-6.1 mmHg and 62.8+/-8.1 mmHg after 30-60 minutes using Maras powder in the
      Maras powder users and the controls, respectively. Both systolic and diastolic
      blood pressures after 30-60 minutes using Maras powder were significantly higher
      in the Maras powder users (p<0.001). Carotid intima media thickness was
      significantly correlated with systolic blood pressure (r=0.613, p<0.001) and
      diastolic blood pressure (r=0.612, p<0.001). CONCLUSIONS: Carotid intima media
      thickness was higher in Maras powder users than in nonusers of the powder.
      Increased carotid intima media thickness can be associated with an immediate
      increase in systolic and diastolic blood pressures. Therefore, attempts to
      increase public awareness about smoking should also be directed towards
      prevention of Maras powder use.

PMID- 24129169
TI  - Targeting of Rho kinase ameliorates impairment of diabetic endothelial function
      in intrarenal artery.
AB  - Endothelial dysfunction in kidney vasculature is the initial and key element for
      nephropathy in diabetes mellitus. Accumulating evidence suggests the protective
      role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS
      activity and NO production. However, the role of Rho kinase in diabetes-related
      endothelial dysfunction in kidney vasculature and the relevant mechanisms remain
      unknown. We assessed whether pharmacological inhibition of Rho kinase attenuates
      endothelial dysfunction in intrarenal arteries from type 1 diabetic rats.
      Fasudil, a Rho kinase inhibitor effectively decreased the phosphorylated level of
      MYPT1 without affecting the expression of ROCKs in the kidney. Fasudil treatment
      showed no improvement in diabetes-related abnormality in metabolic indices, but
      it significantly ameliorated endothelial dysfunction in intrarenal arteries and
      lessened the mesangial matrix expansion in the kidney cortex. Mechanistically,
      superoxide production in the intrarenal artery and NOX4 member of NADPH oxidase
      in the renal cortex that contribute to diabetic nephropathy were also prevented
      by the Rho kinase inhibitor. In conclusion, the present results indicate that Rho
      kinase is involved in endothelial dysfunction in type 1 diabetes via enhancement
      of oxidative stress and provides new evidence for Rho kinase inhibitors as
      potential therapeutic agents for the treatment of diabetic nephropathy. 

PMID- 24129170
TI  - Physiological and proteomic responses of diploid and tetraploid black locust
      (Robinia pseudoacacia L.) subjected to salt stress.
AB  - Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress.
      Here, we compared morphological, physiological, ultrastructural, and proteomic
      traits of leaves in tetraploid black locust and its diploid relatives under salt
      stress. The results showed that diploid (2*) plants suffered from greater
      negative effects than those of tetraploid (4*) plants. After salt treatment,
      plant growth was inhibited, photosynthesis was reduced, reactive oxygen species,
      malondialdehyde content, and relative electrolyte leakage increased, and defense
      related enzyme activities decreased in 2* compared to those in 4*. In addition,
      salt stress resulted in distorted chloroplasts, swollen thylakoid membranes,
      accumulation of plastoglobules, and increased starch grains in 2* compared to
      those in 4*. However, 4* developed diverse responses under salt stress. A
      comparative proteomic analysis revealed that 41 and 37 proteins were
      differentially expressed in 2* and 4*, respectively. These proteins were mainly
      involved in photosynthesis, stress and defense, energy, metabolism,
      transcription/translation, and transportation. Distinct patterns of protein
      changes between 2* and 4* were analyzed. Collectively, our results suggest that
      the plants showed significantly different responses to salt stress based on
      ploidy level of the plant. The 4* possessed a better salt protection mechanism
      than that of 2*, suggesting salt tolerance in the polyploid plant. 

PMID- 24129171
TI  - MicroRNA expression profiling of the porcine developing hypothalamus and
      pituitary tissue.
AB  - MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important
      roles in gene expressions at transcriptional and post-transcriptional stages in
      mammalian brain. So far, a growing number of porcine miRNAs and their function
      have been identified, but little is known regarding the porcine developing
      hypothalamus and pituitary. In the present study, Solexa sequencing analysis
      showed 14,129,397 yielded reads, 6,680,678 of which were related to 674 unique
      miRNAs. After a microarray assay, we detected 175 unique miRNAs in the
      hypothalamus, including 136 previously known miRNAs and 39 novel candidates,
      while a total of 140 miRNAs, including 104 known and 36 new candidate miRNAs,
      were discovered in pituitary. More importantly, 37 and 30 differentially
      expressed miRNAs from several developmental stages of hypothalamus and pituitary
      were revealed, respectively. The 37 differentially expressed miRNAs in
      hypothalamus represented 6 different expression patterns, while the 30
      differentially expressed miRNAs in pituitary represented 7 different expression
      patterns. To clarify potential target genes and specific functions of these
      differentially expressed miRNAs in hypothalamus and pituitary, TargetScan and
      Gorilla prediction tools were then applied. The current functional analysis
      showed that the differentially expressed miRNAs in hypothalamus and pituitary
      shared many biological processes, with the main differences being found in tissue
      specific processes including: CDP-diacylglycerol biosynthetic/metabolic process;
      phosphatidic acid biosynthetic/metabolic process; energy reserve metabolic
      process for hypothalamus; adult behavior; sterol transport/homeostasis; and
      cholesterol/reverse cholesterol transport for pituitary. Overall, this study
      identified miRNA profiles and differentially expressed miRNAs among various
      developmental stages in hypothalamus and pituitary and indicated miRNA profiles
      change with age and brain location, enhancing our knowledge about spatial and
      temporal expressions of miRNAs in the porcine developing brain. 

PMID- 24129172
TI  - Strengths and weaknesses of recently engineered red fluorescent proteins
      evaluated in live cells using fluorescence correlation spectroscopy.
AB  - The scientific community is still looking for a bright, stable red fluorescent
      protein (FP) as functional as the current best derivatives of green fluorescent
      protein (GFP). The red FPs exploit the reduced background of cells imaged in the
      red region of the visible spectrum, but photophysical short comings have limited
      their use for some spectroscopic approaches. Introduced nearly a decade ago,
      mCherry remains the most often used red FP for fluorescence correlation
      spectroscopy (FCS) and other single molecule techniques, despite the advent of
      many newer red FPs. All red FPs suffer from complex photophysics involving
      reversible conversions to a dark state (flickering), a property that results in
      fairly low red FP quantum yields and potential interference with spectroscopic
      analyses including FCS. The current report describes assays developed to
      determine the best working conditions for, and to uncover the shortcoming of,
      four recently engineered red FPs for use in FCS and other diffusion and
      spectroscopic studies. All five red FPs assayed had potential shortcomings
      leading to the conclusion that the current best red FP for FCS is still mCherry.
      The assays developed here aim to enable the rapid evaluation of new red FPs and
      their smooth adaptation to live cell spectroscopic microscopy and nanoscopy. 

PMID- 24129174
TI  - Molecular study of a Hoxa2 gain-of-function in chondrogenesis: a model of
      idiopathic proportionate short stature.
AB  - In a previous study using transgenic mice ectopically expressing Hoxa2 during
      chondrogenesis, we associated the animal phenotype to human idiopathic
      proportionate short stature. Our analysis showed that this overall size reduction
      was correlated with a negative influence of Hoxa2 at the first step of
      endochondral ossification. However, the molecular pathways leading to such
      phenotype are still unknown. Using protein immunodetection and histological
      techniques comparing transgenic mice to controls, we show here that the
      persistent expression of Hoxa2 in chondrogenic territories provokes a general
      down-regulation of the main factors controlling the differentiation cascade, such
      as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm
      the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also
      show a selective effect of Hoxa2 on endochondral ossification processes since
      Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively.
      Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype
      mimicking human idiopathic conditions, our results give an insight into
      understanding proportionate short stature pathogenesis by highlighting molecular
      factors whose combined deregulation may be involved in such a disease. 

PMID- 24129175
TI  - Genetic diversity and population differentiation of Calanthe tsoongiana, a rare
      and endemic orchid in China.
AB  - Calanthe tsoongiana is a rare terrestrial orchid endemic to China, and this
      species has experienced severe habitat loss and fragmentation. Inter-simple
      sequence repeat (ISSR) markers were employed to assess the genetic diversity and
      differentiation of six populations of C. tsoongiana. Based on 124 discernible
      fragments yielded by eleven selected primers, high genetic diversity was revealed
      at the species level; however, genetic diversity at the population level was
      relatively low. High-level genetic differentiation among populations was detected
      based on analysis of molecular variance (AMOVA), indicating potential limited
      gene flow. No significant relationship was observed between genetic and
      geographic distances among the sampled populations. These results suggested that
      restricted gene flow might be due to habitat fragmentation and reduced population
      size as a result of human activities. Based on the findings, several conservation
      strategies were proposed for the preservation of this threatened species. 

PMID- 24129173
TI  - HKT transporters--state of the art.
AB  - The increase in soil salinity poses a serious threat to agricultural yields.
      Under salinity stress, several Na+ transporters play an essential role in Na+
      tolerance in plants. Amongst all Na+ transporters, HKT has been shown to have a
      crucial role in both mono and dicotyledonous plants in the tolerance to salinity
      stress. Here we present an overview of the physiological role of HKT transporters
      in plant Na+ homeostasis. HKT regulation and amino acids important to the correct
      function of HKT transporters are reviewed. The functions of the most recently
      characterized HKT members from both HKT1 and HKT2 subfamilies are also discussed.
      Topics that still need to be studied in future research (e.g., HKT regulation) as
      well as research suggestions (e.g., generation of HKT mutants) are addressed.

PMID- 24129176
TI  - Characterization of 42 microsatellite markers from poison ivy, Toxicodendron
      radicans (Anacardiaceae).
AB  - Poison ivy, Toxicodendron radicans, and poison oaks, T. diversilobum and T.
      pubescens, are perennial woody species of the Anacardiaceae and are poisonous,
      containing strong allergens named urushiols that cause allergic contact
      dermatitis. Poison ivy is a species distributed from North America to East Asia,
      while T. diversilobum and T. pubescens are distributed in western and eastern
      North America, respectively. Phylogreography and population structure of these
      species remain unclear. Here, we developed microsatellite markers, via
      constructing a magnetic enriched microsatellite library, from poison ivy. We
      designed 51 primer pairs, 42 of which successfully yielded products that were
      subsequently tested for polymorphism in poison oak, and three subspecies of
      poison ivy. Among the 42 loci, 38 are polymorphic, while 4 are monomorphic. The
      number of alleles and the expected heterozygosity ranged from 1 to 12 and from
      0.10 to 0.87, respectively, in poison ivy, while varied from 2 to 8 and, from
      0.26 to 0.83, respectively in poison oak. Genetic analysis revealed distinct
      differentiation between poison ivy and poison oak, whereas slight genetic
      differentiation was detected among three subspecies of poison ivy. These highly
      polymorphic microsatellite fingerprints enable biologists to explore the
      population genetics, phylogeography, and speciation in Toxicodendron. 

PMID- 24129177
TI  - An emerging role for long non-coding RNA dysregulation in neurological disorders.
AB  - A novel class of transcripts, long non coding RNAs (lncRNAs), has recently
      emerged as key players in several biological processes, including dosage
      compensation, genomic imprinting, chromatin regulation, embryonic development and
      segmentation, stem cell pluripotency, cell fate determination and potentially
      many other biological processes, which still are to be elucidated. LncRNAs are
      pervasively transcribed in the genome and several lines of evidence correlate
      dysregulation of different lncRNAs to human diseases including neurological
      disorders. Although their mechanisms of action are yet to be fully elucidated,
      evidence suggests lncRNA contributions to the pathogenesis of a number of
      diseases. In this review, the current state of knowledge linking lncRNAs to
      different neurological disorders is discussed and potential future directions are
      considered. 

PMID- 24129178
TI  - Inhibition of melanogenesis by gallic acid: possible involvement of the PI3K/Akt,
      MEK/ERK and Wnt/beta-catenin signaling pathways in B16F10 cells.
AB  - Gallic acid is one of the major flavonoids found in plants. It acts as an
      antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer
      properties. In this study, we investigated the effects of gallic acid on
      melanogenesis, including the activation of melanogenesis signaling pathways.
      Gallic acid significantly inhibited both melanin synthesis and tyrosinase
      activity in a dose- and time-dependent manner, and decreased the expression of
      melanogenesis-related proteins, such as microphthalmia-associated transcription
      factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome
      tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and
      activating melanogenesis inhibitory proteins such as Akt and mitogen-activated
      protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using
      inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the
      hypopigmentation effect was suppressed, and the gallic acid-initiated activation
      of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3beta and
      p-beta-catenin expression but down-regulated p-GSK3beta. Moreover, GSK3beta
      specific inhibitor (SB216763) restored gallic acid-induced melanin reduction.
      These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of
      Wnt/beta-catenin signaling pathways is involved in the melanogenesis signaling
      cascade, and that activation by gallic acid reduces melanin synthesis via down
      regulation of MITF and its downstream signaling pathway. In conclusion, gallic
      acid may be a potentially agent for the treatment of certain skin conditions. 

PMID- 24129179
TI  - Twist and miR-34a are involved in the generation of tumor-educated myeloid
      derived suppressor cells.
AB  - Tumors can induce the generation and accumulation of immunosuppressive cells such
      as myeloid-derived suppressor cells in the tumor microenvironment, contributing
      to tumor immunological escapes. Many studies have demonstrated that multiple
      factors could induce myeloid precursor cells into myeloid-derived suppressor
      cells, not dendritic cells. In our study, we found that tumor supernatants could
      induce the generation of myeloid-derived suppressor cells by disturbing the
      development of dendritic cells. Twist and miR-34a may regulate the effect of
      tumor cells inducing myeloid-derived suppressor cells via TGF-beta and/or IL-10. 

PMID- 24129180
TI  - Transcriptome comparative profiling of barley eibi1 mutant reveals pleiotropic
      effects of HvABCG31 gene on cuticle biogenesis and stress responsive pathways.
AB  - Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain
      leaf water, a phenotype associated with reduced cutin deposition and a thin
      cuticle. To better understand how such a mutant plant survives, we performed a
      genome-wide gene expression analysis. The leaf transcriptomes between the near
      isogenic lines eibi1 and the wild type were compared using the 22-k Barley1
      Affymetrix microarray. We found that the pleiotropic effect of the single gene
      HvABCG31 mutation was linked to the co-regulation of metabolic processes and
      stress-related system. The cuticle development involved cytochrome P450 family
      members and fatty acid metabolism pathways were significantly up-regulated by the
      HvABCG31 mutation, which might be anticipated to reduce the levels of cutin
      monomers or wax and display conspicuous cuticle defects. The candidate genes for
      responses to stress were induced by eibi1 mutant through activating the jasmonate
      pathway. The down-regulation of co-expressed enzyme genes responsible for DNA
      methylation and histone deacetylation also suggested that HvABCG31 mutation may
      affect the epigenetic regulation for barley development. Comparison of
      transcriptomic profiling of barley under biotic and abiotic stresses revealed
      that the functions of HvABCG31 gene to high-water loss rate might be different
      from other osmotic stresses of gene mutations in barley. The transcriptional
      profiling of the HvABCG31 mutation provided candidate genes for further
      investigation of the physiological and developmental changes caused by the
      mutant. 

PMID- 24129181
TI  - Significant overexpression of DVL1 in Taiwanese colorectal cancer patients with
      liver metastasis.
AB  - Undetected micrometastasis plays a key role in the metastasis of cancer in
      colorectal cancer (CRC) patients. The aim of this study is to identify a
      biomarker of CRC patients with liver metastasis through the detection of
      circulating tumor cells (CTCs). Microarray and bioinformatics analysis of 10 CRC
      cancer tissue specimens compared with normal adjacent tissues revealed that 31
      genes were up-regulated (gene expression ratio of cancer tissue to paired normal
      tissue > 2) in the cancer patients. We used a weighted enzymatic chip array
      (WEnCA) including 31 prognosis-related genes to investigate CTCs in 214
      postoperative stage I-III CRC patients and to analyze the correlation between
      gene expression and clinico-pathological parameters. We employed the
      immunohistochemistry (IHC) method with polyclonal mouse antibody against DVL1 to
      detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in
      19.16% (41/214) of the patients. Using univariate analysis and multivariate
      proportional hazards regression analysis, we found that DVL1 mRNA overexpression
      had a significant, independent predictive value for liver metastasis in CRC
      patients (OR: 5.764; 95% CI: 2.588-12.837; p < 0.0001 on univariate analysis; OR:
      3.768; 95% CI: 1.469-9.665; p = 0.006 on multivariate analysis). IHC staining of
      the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of
      CRC cells. High expression of DVL1 was observed in 55% (33/60) of CRC tumor
      specimens and was associated significantly with tumor depth, perineural invasion
      and liver metastasis status (all p < 0.05). Our experimental results demonstrated
      that DVL1 is significantly overexpressed in CRC patients with liver metastasis,
      leading us to conclude that DVL1 could be a potential prognostic and predictive
      marker for CRC patients. 

PMID- 24129183
TI  - Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6
      cell proliferation and modulates the expression of fibrogenic factors.
AB  - Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs),
      which synthesize excess extracellular matrix and contribute to the development of
      liver fibrosis. In a prior study we tested the effect of combined treatment with
      taurine, epigallocatechin gallate and genistein on the development of alcohol
      induced liver fibrosis in vitro. In this study, the biological activity of the
      combination of these molecules was assessed by measuring its effect on cell
      proliferation, fibrosis-related gene expression, and proteomic expression
      profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated
      with different concentrations of the drug combination taurine, epigallocatechin
      gallate and genistein. Cell proliferation was evaluated by MTT assay.
      Transforming growth factor beta1 (TGF-beta1), collagen type I (Col-I), matrix
      metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2
      (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription
      PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS.
      Combined drug treatment significantly inhibited cell proliferation and TGF-beta1,
      Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the
      expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were
      identified. The intensities of 10 protein peaks were downregulated and two
      protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In
      conclusion, combined drug treatment with taurine, epigallocatechin gallate and
      genistein can inhibit HSC proliferation, and impact fibrosis-related gene and
      protein expression. The antifibrotic effects of this drug combination may be due
      to its effects on the expression of fibrogenic genes. 

PMID- 24129182
TI  - Advances in the research of melatonin in autism spectrum disorders: literature
      review and new perspectives.
AB  - Abnormalities in melatonin physiology may be involved or closely linked to the
      pathophysiology and behavioral expression of autistic disorder, given its role in
      neurodevelopment and reports of sleep-wake rhythm disturbances, decreased
      nocturnal melatonin production, and beneficial therapeutic effects of melatonin
      in individuals with autism. In addition, melatonin, as a pineal gland hormone
      produced from serotonin, is of special interest in autistic disorder given
      reported alterations in central and peripheral serotonin neurobiology. More
      specifically, the role of melatonin in the ontogenetic establishment of circadian
      rhythms and the synchronization of peripheral oscillators opens interesting
      perspectives to ascertain better the mechanisms underlying the significant
      relationship found between lower nocturnal melatonin excretion and increased
      severity of autistic social communication impairments, especially for verbal
      communication and social imitative play. In this article, first we review the
      studies on melatonin levels and the treatment studies of melatonin in autistic
      disorder. Then, we discuss the relationships between melatonin and autistic
      behavioral impairments with regard to social communication (verbal and non-verbal
      communication, social interaction), and repetitive behaviors or interests with
      difficulties adapting to change. In conclusion, we emphasize that randomized
      clinical trials in autism spectrum disorders are warranted to establish potential
      therapeutic efficacy of melatonin for social communication impairments and
      stereotyped behaviors or interests. 

PMID- 24129184
TI  - The key enzyme of the sialic acid metabolism is involved in embryoid body
      formation and expression of marker genes of germ layer formation.
AB  - The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase
      (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are
      negatively charged nine carbon amino sugars and are found on most glycoproteins
      and many glycolipids in terminal positions, where they are involved in a variety
      of biological important molecular interactions. Inactivation of the GNE by
      homologous recombination results in early embryonic lethality in mice. Here, we
      report that GNE-deficient embryonic stem cells express less differentiation
      markers compared to wild-type embryonic stem cells. As a result, GNE-deficient
      embryonic stem cells fail to form proper embryoid bodies (EB) within the first
      day of culture. However, when culturing these cells in the presence of sialic
      acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In
      contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient
      embryonic stem cells proliferate faster and form larger EBs without any change in
      the expression of markers of the germ layers. 

PMID- 24129185
TI  - miRNA-205 affects infiltration and metastasis of breast cancer.
AB  - BACKGROUND: An increasing number of studies have shown that miRNAs are commonly
      deregulated in human malignancies, but little is known about the function of
      miRNA-205 (miR-205) in human breast cancer. The present study investigated the
      influence of miR-205 on breast cancer malignancy. METHODS: The expression level
      of miR-205 in the MCF7 breast cancer cell line was determined by quantitative
      (q)RT-PCR. We then analyzed the expression of miR-205 in breast cancer and paired
      non-tumor tissues. Finally, the roles of miR-205 in regulating tumor
      proliferation, apoptosis, migration, and target gene expression were studied by
      MTT assay, flow cytometry, qRT-PCR, Western blotting and luciferase assay.
      RESULTS: miR-205 was downregulated in breast cancer cells or tissues compared
      with normal breast cell lines or non-tumor tissues. Overexpression of miR-205
      reduced the growth and colony-formation capacity of MCF7 cells by inducing
      apoptosis. Overexpression of miR-205 inhibited MCF7 cell migration and
      invasiveness. By bioinformation analysis, miR-205 was predicted to bind to the 3'
      untranslated regions of human epidermal growth factor receptor (HER)3 mRNA, and
      upregulation of miR-205 reduced HER3 protein expression. CONCLUSION: miR-205 is a
      tumor suppressor in human breast cancer by post-transcriptional inhibition of
      HER3 expression.

PMID- 24129187
TI  - HIV-1 TAT-mediated protein transduction of human HPRT into deficient cells.
AB  - Lesch-Nyhan disease (LND) is a severe and incurable X-linked genetic syndrome
      caused by the deficiency of hypoxanthine-guanine phosphoribosyltransferase
      (HPRT), resulting in severe alterations of central nervous system, hyperuricemia
      and subsequent impaired renal functions. Therapeutic options consist in
      supportive care and treatments of complications, but the disease remains largely
      untreatable. Enzyme replacement of the malfunctioning cytosolic protein might
      represent a possible therapeutic approach for the LND treatment. Protein
      transduction domains, such as the TAT peptide derived from HIV TAT protein, have
      been used to transduce macromolecules into cells in vitro and in vivo. The
      present study was aimed to the generation of TAT peptide fused to human HPRT for
      cell transduction in enzyme deficient cells. Here we document the construction,
      expression and delivery of a functional HPRT enzyme into deficient cells by TAT
      transduction domain and by liposome mediated protein transfer. With this approach
      we demonstrate the correction of the enzymatic defect in HPRT deficient cells.
      Our data show for the first time the feasibility of the enzyme replacement
      therapy for the treatment of LND. 

PMID- 24129186
TI  - Chorein, the protein responsible for chorea-acanthocytosis, interacts with beta
      adducin and beta-actin.
AB  - Chorea-acanthocytosis (ChAc) is an autosomal, recessive hereditary disease
      characterized by striatal neurodegeneration and acanthocytosis, and caused by
      loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A)
      gene. VPS13A encodes chorein whose physiological function at the molecular level
      is poorly understood. In this study, we show that chorein interacts with beta
      adducin and beta-actin. We first compare protein expression in human erythrocyte
      membranes using proteomic analysis. Protein levels of beta-adducin isoform 1 and
      beta-actin are markedly decreased in erythrocyte membranes from a ChAc patient.
      Subsequent co-immunoprecipitation (co-IP) and reverse co-IP assays using extracts
      from chorein-overexpressing human embryonic kidney 293 (HEK293) cells, shows that
      beta-adducin (isoforms 1 and 2) and beta-actin interact with chorein.
      Immunocytochemical analysis using chorein-overexpressing HEK293 cells
      demonstrates co-localization of chorein with beta-adducin and beta-actin. In
      addition, immunoreactivity of beta-adducin isoform 1 is significantly decreased
      in the striatum of gene-targeted ChAc-model mice. Adducin and actin are membrane
      cytoskeletal proteins, involved in synaptic function. Expression of beta-adducin
      is restricted to the brain and hematopoietic tissues, corresponding to the main
      pathological lesions of ChAc, and thereby implicating beta-adducin and beta-actin
      in ChAc pathogenesis. 

PMID- 24129188
TI  - Periostin inhibits hypoxia-induced apoptosis in human periodontal ligament cells
      via TGF-beta signaling.
AB  - Periostin (POSTN) is an extracellular matrix protein expressed predominantly in
      periodontal ligament (PDL) cells. The aim of this study was to investigate the
      effects of POSTN on human PDL cell apoptosis under hypoxic conditions. The
      percentage of apoptotic PDL cells under hypoxia was increased significantly when
      the endogenous POSTN gene was silenced using siRNA, but decreased when cells were
      treated with recombinant human POSTN (rhPOSTN), or when mouse Postn was
      overexpressed in vitro. Silencing POSTN during hypoxia decreased the expression
      of HIF prolyl-hydroxylase 2 (PHD2), but increased HIF-1alpha protein level.
      Conversely, treating hypoxic cells with rhPOSTN or overexpressing Postn increased
      PHD2 expression but decreased HIF-1alpha levels. The addition of rhPOSTN in the
      absence of a TGF-beta receptor inhibitor (SB525334) significantly decreased
      hypoxia-induced apoptosis, while the effects of rhPOSTN were abolished when cells
      were co-treated with SB525334. Consistent with this, the phosphorylation of SMAD2
      was increased in hypoxic PDL cells by the knockdown of POSTN, but decreased by
      treatment with rhPOSTN. Under normoxia, the PHD2 expression, HIF-1alpha level,
      and apoptosis were unaffected by POSTN siRNA, rhPOSTN, or Postn overexpression.
      These findings suggest that, under hypoxic conditions, POSTN regulates PHD2
      expression and HIF-1alpha levels by modulating TGF-beta1 signaling, leading to
      decreased apoptosis. 

PMID- 24129189
TI  - Effect of Liraglutide on endoplasmic reticulum stress in diabetes.
AB  - Endoplasmic reticulum (ER) stress is associated with the development of diabetes.
      The present study sought to investigate the effect of Liraglutide, a glucagon
      like peptide 1 analogue, on ER stress in beta-cells. We found that Liraglutide
      protected the pancreatic INS-1 cells from thapsigargin-induced ER stress and the
      ER stress associated cell apoptosis, mainly by suppressing the PERK and IRE1
      pathways. We further tested the effects of Liraglutide in the Akita mouse, an ER
      stress induced type 1 diabetes model. After administration of Liraglutide for
      8weeks, p-eIF2alpha and p-JNK were significantly decreased in the pancreas of the
      Akita mouse, while the treatment showed no significant impact on the levels of
      insulin of INS-cells. Taken together, our findings suggest that Liraglutide may
      protect pancreatic cells from ER stress and its related cell death. 

PMID- 24129190
TI  - Involvement of a di-leucine motif in targeting of ABCC1 to the basolateral plasma
      membrane of polarized epithelial cells.
AB  - Localization of ATP-binding cassette transporter isoform C1 (ABCC1) to the
      basolateral membrane of polarized cells is crucial for export of a variety of
      cellular metabolites; however, the mechanism regulating basolateral targeting of
      the transporter is poorly understood. Here we describe identification of a
      basolateral targeting signal in the first cytoplasmic loop domain (CLD1) of human
      ABCC1. Comparison of the CLD1 amino acid sequences from ABCC1 to ABCC2 revealed
      that ABCC1 possesses a characteristic sequence, E(295)EVEALI(301), which is
      comprised of a cluster of acidic glutamate residues followed by a di-leucine
      motif. This characteristic sequence is highly conserved among vertebrate ABCC1
      orthologs and is positioned at a site that is structurally equivalent to the
      apical targeting signal previously described in ABCC2. Alanine scanning
      mutagenesis of this sequence in full-length human ABCC1 showed that both L(300)
      and I(301) residues were required for basolateral targeting of ABCC1 in polarized
      HepG2 and MDCK cells. Conversely, E(295), E(296), and E(298) residues were not
      required for basolateral localization of the transporter. Therefore, a di-leucine
      motif within the CLD1 is a basolateral targeting determinant of ABCC1. 

PMID- 24129191
TI  - Retention of alpha-helical structure by HDL mimetic peptide ATI-5261 upon
      extensive dilution represents an important determinant for stimulating ABCA1
      cholesterol efflux with high efficiency.
AB  - ATI-5261 is a novel, single-helix peptide that stimulates cellular cholesterol
      efflux with high potency similar to native apolipoproteins on a molar basis.
      Presently we investigated structural features of the peptide that conferred
      cholesterol efflux activity. Analogs of ATI-5261 with amino acids arranged in
      reverse order or with individual arginine (R) to glutamine (Q) substitutions
      (i.e. R3Q, R14Q, or R23Q) stimulated ABCA1 dependent cholesterol efflux similar
      to ATI-5261. Consequently, neither the presence of specific positively charged
      residues nor their specific arrangement along the length of the peptide was
      necessary for mediating cholesterol efflux. Similarly, peptides composed of all d
      amino acids stimulated cholesterol efflux efficiently, indicating a
      stereospecific component was not required for promotion of cholesterol efflux
      from macrophages. Removal of two or more positively charged residues (R3, 14->Q
      and R3, 14, 23->Q) however, greatly reduced the ability of ATI-5261 to mediate
      cellular cholesterol efflux. This was accompanied by a loss of alpha-helical
      structure upon dilution, indicating the secondary structure of individual peptide
      strands was important for stimulating cholesterol efflux. Surprisingly, peptides
      with removal of two or more positively charged residues retained the ability to
      bind phospholipid and adopt an alpha-helical structure. These data indicate that
      the propensity of a hydrophobic peptide to form an amphipathic alpha-helix is not
      sufficient to mediate cellular cholesterol efflux. Efficient stimulation of
      cholesterol efflux requires that ATI-5261 retain alpha-helical structure upon
      dilution. 

PMID- 24129192
TI  - FABP3 and brown adipocyte-characteristic mitochondrial fatty acid oxidation
      enzymes are induced in beige cells in a different pathway from UCP1.
AB  - Cold exposure and beta3-adrenergic receptor agonist (CL316,243) treatment induce
      the production of beige cells, which express brown adipocytes(BA)-specific UCP1
      protein, in white adipose tissue (WAT). It remains unclear whether the beige
      cells, which have different gene expression patterns from BA, express BA
      characteristic fatty acid oxidation (FAO) proteins. Here we found that 5 day cold
      exposure and CL316,243 treatment of WAT, but not CL316,243 treatment of primary
      adipocytes of C57BL/6J mice, increased mRNA levels of BA-characteristic FAO
      proteins. These results suggest that BA-characteristic FAO proteins are induced
      in beige cells in a different pathway from UCP1.

PMID- 24129193
TI  - A testis-specific serine protease, Prss41/Tessp-1, is necessary for the
      progression of meiosis during murine in vitro spermatogenesis.
AB  - The function of protease during male meiosis has not been well studied. We
      previously cloned and characterized four testis-specific serine proteases in the
      mouse testis. One of the proteases, Prss41/Tessp-1, was expressed in the germ and
      Sertoli cell. This time, to examine the involvement of Prss41/Tessp-1 in
      spermatogenesis, we conducted the organ culture of testis fragments in the
      presence of the anti-Prss41/Tessp-1 antibody. Because in the Sertoli cell, the
      Prss41/Tessp-1 protein was mostly associated with the membrane of intracellular
      organelles by glycosylphosphatidylinositol, the antibody was expected to affect
      Prss41/Tessp-1 at the plasma membrane of spermatogonia. By adding the antibody,
      the number of germ cells was decreased in some seminiferous tubules. The marker
      genes expression strongly suggested that meiosis was arrested at spermatogonia,
      and the number of apoptotic germ cells increased by terminal deoxynucleotidyl
      transferase dUTP nick end labeling assay. These data indicated that Prss41/Tessp
      1 was necessary for the progression of meiosis at the stage of spermatogonia
      during in vitro spermatogenesis. Together with our previous study, the current
      results suggest that the Prss/Tessp proteases are important for the progression
      of meiosis at each stage. 

PMID- 24129194
TI  - Evaluation of bacterial motility from non-Gaussianity of finite-sample
      trajectories using the large deviation principle.
AB  - Motility of bacteria is usually recognized in the trajectory data and compared
      with Brownian motion, but the diffusion coefficient is insufficient to evaluate
      it. In this paper, we propose a method based on the large deviation principle. We
      show that it can be used to evaluate the non-Gaussian characteristics of model
      Escherichia coli motions and to distinguish combinations of the mean running
      duration and running speed that lead to the same diffusion coefficient. Our
      proposed method does not require chemical stimuli to induce the chemotaxis in a
      specific direction, and it is applicable to various types of self-propelling
      motions for which no a priori information of, for example, threshold parameters
      for run and tumble or head/tail direction is available. We also address the issue
      of the finite-sample effect on the large deviation quantities, but we propose to
      make use of it to characterize the nature of motility. 

PMID- 24129195
TI  - Efficacy and safety of lacosamide in infants and young children with refractory
      focal epilepsy.
AB  - BACKGROUND: Lacosamide is effective and well-tolerated antiepileptic drug (AED)
      in both children and adults. AIM: This multicentric, prospective study
      investigates the efficacy and safety of lacosamide adjunctive therapy in children
      aged less than four years presenting with refractory focal seizures. METHODS:
      Lacosamide was added to the baseline therapy at a starting dose of 1-2 mg/kg/day
      and titrated to the final dose, ranging from 7 to 15.5 mg/kg/day. Efficacy was
      evaluated after a three-month period of therapy. When possible, we compared the
      initial efficacy and the retention after a minimum of 12 months of lacosamide,
      with regard to loss of efficacy (defined as the return to the baseline seizure
      frequency). RESULTS: Twenty-four children were enrolled in the study. Mean age
      was 2.7 years. After a minimum three-month period of lacosamide add-on therapy,
      ten (42%) patients were responders (more than a 50% decrease in seizure
      frequency), of whom 4 (17%) became seizure free. Retention rate, after a minimum
      of 12 months of lacosamide, was evaluated in a group of 18 patients. In the
      latter group, eight patients (44%) were initial responders (three of whom seizure
      free). After 12 months of follow-up, four of them (22%) maintained the
      improvement, 2 (11%) of whom remained seizure free. A loss of efficacy was
      observed in 4 of the initial responders (50%). Adverse events were seen in 8
      (33%) patients. CONCLUSION: We conclude that lacosamide is an effective and a
      well-tolerated antiepileptic drug in an etiologically wide range of focal
      seizures. Therefore, lacosamide might represent a possible therapeutic option in
      infants and young children affected by uncontrolled focal epilepsy.

PMID- 24129196
TI  - Colorectal cancer prevention in the Czech Republic: time trends in performance
      indicators and current situation after 10 years of screening.
AB  - The incidence and mortality of colorectal cancer (CRC) in the Czech Republic is
      significant. The National CRC Screening Program started in 2000 and was further
      enhanced in 2009. In 2010, the European Guidelines were introduced. The aim of
      the present trend study was to evaluate the quality of the Czech National
      Colorectal Cancer Screening Program using early performance and long-term impact
      indicators. The screening program has been assessed using data from three
      sources: the Czech National Cancer Registry, the Czech National Reference Centre,
      and the Czech CRC Screening Registry. The data were compared with a set of
      recommended quality control indicators. Between 2006 and 2010, a total of 1 881
      299 fecal occult blood tests were performed, of which 87 397 were positive
      (4.6%). Until 2011, a total of 68 527 fecal occult blood test follow-up
      colonoscopies were performed. In addition, between 2009 and 2011, a total of 10
      309 screening colonoscopies were performed. As a result, a total of 25 255
      adenomas (32.0% rate) and 3379 CRCs (4.3% rate) were detected. A trend of cancer
      detection in earlier stages has been observed. The overall program coverage has
      increased to 22.7% of the target population in 2010. The majority of European
      guidelines' quality indicators for nonpopulation-based programs were implemented
      in the Czech National CRC Screening program. An improvement in program management
      was accompanied by an increase in coverage as well as other performance
      indicators. 

PMID- 24129197
TI  - Clinicians and researchers in diabetes: opportunities in nutrition policy and
      advocacy.

PMID- 24129199
TI  - Two faces, two languages: an fMRI study of bilingual picture naming.
AB  - This fMRI study explores how nonlinguistic cues modulate lexical activation in
      the bilingual brain. We examined the influence of face race on bilingual language
      production in a picture-naming paradigm. Chinese-English bilinguals were
      presented with pictures of objects and images of faces (Asian or Caucasian).
      Participants named the picture in their first or second language (Chinese or
      English) in separate blocks. Face race and naming language were either congruent
      (e.g., naming in Chinese when seeing an Asian face) or incongruent (e.g., naming
      in English when seeing an Asian face). Our results revealed that face cues
      facilitate naming when the socio-cultural identity of the face is congruent with
      the naming language. The congruence effects are reflected as effective
      integration of lexical and facial cues in key brain regions including IFG, MFG,
      ACC, and caudate. Implications of the findings in light of theories of language
      processing and cultural priming are discussed. 

PMID- 24129198
TI  - Caffeine protects neuronal cells against injury caused by hyperoxia in the
      immature brain.
AB  - Caffeine administered to preterm infants has been shown to reduce rates of
      cerebral palsy and cognitive delay, compared to placebo. We investigated the
      neuroprotective potential of caffeine for the developing brain in a neonatal rat
      model featuring transient systemic hyperoxia. Using 6-day-old rat pups, we found
      that after 24 and 48h of 80% oxygen exposure, apoptotic (TUNEL(+)) cell numbers
      increased in the cortex, hippocampus, and central gray matter, but not in the
      hippocampus or dentate gyrus. In the dentate gyrus, high oxygen exposure led to a
      decrease in the number of proliferating (Ki67(+)) cells and the number of Ki67(+)
      cells double staining for nestin (immature neurons), doublecortin (progenitors),
      and NeuN (mature neurons). Absolute numbers of nestin(+), doublecortin(+), and
      NeuN(+) cells also decreased after hyperoxia. This was mirrored in a decline of
      transcription factors expressed in immature neurons (Pax6, Sox2), progenitors
      (Tbr2), and mature neurons (Prox1, Tbr1). Administration of a single dose of
      caffeine (10mg/kg) before high oxygen exposure almost completely prevented these
      effects. Our findings suggest that caffeine exerts protection for neonatal
      neurons exposed to high oxygen, possibly via its antioxidant capacity. 

PMID- 24129200
TI  - Early effects of neighborhood density and phonotactic probability of spoken words
      on event-related potentials.
AB  - All current models of spoken word recognition propose that sound-based
      representations of spoken words compete with, or inhibit, one another during
      recognition. In addition, certain models propose that higher probability
      sublexical units facilitate recognition under certain circumstances. Two
      experiments were conducted examining ERPs to spoken words and nonwords
      simultaneously varying in phonotactic probability and neighborhood density.
      Results showed that the amplitude of the P2 potential was greater for high
      probability-density words and nonwords, suggesting an early inhibitory effect of
      neighborhood density. In order to closely examine the role of phonotactic
      probability, effects of initial phoneme frequency were also examined. The latency
      of the P2 potential was shorter for words with high initial-consonant
      probability, suggesting a facilitative effect of phonotactic probability. The
      current results are consistent with findings from previous studies using reaction
      time and eye-tracking paradigms and provide new insights into the time-course of
      lexical and sublexical activation and competition. 

PMID- 24129202
TI  - ERACEing the risk of cerebral embolism from atrial fibrillation ablation.

PMID- 24129203
TI  - Inducible fast ventricular tachycardia after ST-segment--elevation myocardial
      infarction: is ventricular tachycardia ever OK?

PMID- 24129204
TI  - Assessing ventricular scar in tetralogy of Fallot.

PMID- 24129205
TI  - Update on interventional electrophysiology in congenital heart disease: evolving
      solutions for complex hearts.

PMID- 24129206
TI  - Bachmann's bundle: a key player in the development of atrial fibrillation?

PMID- 24129207
TI  - Sudden change from counterclockwise to clockwise flutter during cavotricuspid
      isthmus ablation: what is the mechanism?

PMID- 24129208
TI  - Editor's perspective: spinning wheels: what goes up cannot come down?

PMID- 24129209
TI  - An unusual cause of intermittent broad QRS complexes.

PMID- 24129210
TI  - Editor's perspective: the interatrial septum.

PMID- 24129211
TI  - Fatigue attributable to broken pacemaker header by baseball.

PMID- 24129212
TI  - Investigation of adipocyte proteome during the differentiation of brown
      preadipocytes.
AB  - Brown adipocytes oxidize fatty acids to produce heat in response to cold or
      caloric overfeeding. The motivation and function of the development of brown fat
      may thus counteract obesity, though this remains uncertain. We investigated the
      brown adipocyte proteome by two-dimensional gel electrophoresis followed by mass
      spectrometry. Comparative analyses of proteins focused on total protein spots to
      filter differentially expressed proteins during the differentiation of mouse
      primary brown preadipocytes. A Western blot analysis was performed to verify the
      target proteins. The results indicated that 10 protein spots were differentially
      expressed with significant changes, including the three up-regulated proteins of
      prohibitin, hypoxanthine-guanine phosphoribosyltransferase, and enoyl-CoA
      hydratase protein; the 5 down-regulated proteins of triosephosphate isomerase,
      elongation factor 2, alpha-tropomyosin slow, endophilin-B1, and cofilin-1 (CFL1);
      and the two unequivocally expressed proteins of peroxiredoxin-1 and collagen
      alpha-1(i) chain precursor. We found that during brown adipogenesis, CFL1 has an
      inhibitory effect on brown adipocyte differentiation. The overexpression of CFL1
      inhibited the brown fat deposition and repressed the brown marker genes UCP1,
      PRDM16, PGC-1alpha and PPARgamma via actin dynamics and polymerization. These
      observations may be novel findings that bring new insight into the detailed
      mechanisms of brown adipogenesis and identify possible therapeutic targets for
      anti-obesity. BIOLOGICAL SIGNIFICANCE: We use 2-DE to compare the proteomes of
      adipocytes during the brown adipogenesis of primary mouse preadipocytes. We
      identified 10 proteins that are differentially expressed. Among these, we found
      that the actin binding protein CFL1 inhibits the differentiation of brown
      preadipocytes. CFL1 overexpressing cells showed lower deposition of brown fat
      droplets, and the brown marker genes of UCP1, PRDM16, PGC-1alpha and PPARgamma
      were decreased through actin dynamics and polymerization.

PMID- 24129213
TI  - Effects of using arsenic-iron sludge wastes in brick making.
AB  - The arsenic-iron sludge generated in most of the treatment systems around the
      world is discharged into the nearest watercourse, which leads to accumulative
      rise of arsenic and iron concentrations in water. In this study, attempts were
      made to use the arsenic-iron sludge in making bricks and to analyze the
      corresponding effects on brick properties. The water treatment plant sludge is
      extremely close to brick clay in chemical composition. So, the sludge could be a
      potential substitute for brick clay. This study involved the addition of sludge
      with ratios 3%, 6%, 9% and 12% of the total weight of sludge-clay mixture. The
      physical and chemical properties of the produced bricks were then determined and
      evaluated and compared to control brick made entirely from clay. Results of
      different tests indicated that the sludge proportion and firing temperature were
      the two key factors in determining the quality of bricks. The compressive
      strength of 3%, 6%, 9% and 12% sludge containing brick samples were found to be
      14.1 MPa, 15.1 MPa, 9.4 MPa and 7.1 MPa, respectively. These results indicate
      that the compressive strength of prepared bricks initially increased and then
      decreased with the increase of sludge proportion. Leaching characteristics of
      burnt bricks were determined with the variation of pH at a constant temperature.
      The optimum amount of sludge that could be mixed with clay to produce good
      bonding of clay-sludge bricks was found to be 6% (safely maximum) by weight.

PMID- 24129214
TI  - Pyrolysis of waste animal fats in a fixed-bed reactor: production and
      characterization of bio-oil and bio-char.
AB  - Several animal (lamb, poultry and swine) fatty wastes were pyrolyzed under
      nitrogen, in a laboratory scale fixed-bed reactor and the main products (liquid
      bio-oil, solid bio-char and syngas) were obtained. The purpose of this study is
      to produce and characterize bio-oil and bio-char obtained from pyrolysis of
      animal fatty wastes. The maximum production of bio-oil was achieved at a
      pyrolysis temperature of 500  degrees C and a heating rate of 5  degrees C/min.
      The chemical (GC-MS analyses) and spectroscopic analyses (FTIR analyses) of bio
      oil showed that it is a complex mixture consisting of different classes of
      organic compounds, i.e., hydrocarbons (alkanes, alkenes, cyclic
      compounds...etc.), carboxylic acids, aldehydes, ketones, esters,...etc. According
      to fuel properties, produced bio-oils showed good properties, suitable for its
      use as an engine fuel or as a potential source for synthetic fuels and chemical
      feedstock. Obtained bio-chars had low carbon content and high ash content which
      make them unattractive for as renewable source energy.

PMID- 24129215
TI  - Adolescents' reasons for tanning and appearance motives: a preliminary study.
AB  - We examined adolescents' reasons for tanning and how these relate to appearance
      evaluation and orientation. Two hundred and sixty-four Canadian adolescents (age
      range 15-19 years) in grades 10, 11, and 12 completed a survey that included
      scales measuring their reasons for tanning, appearance evaluation, and appearance
      orientation. It was found that girls and boys differed on four of nine subscales
      measuring reasons for tanning. Girls believed more strongly than boys that
      tanning improved their general appearance and that friends influenced their
      decision to tan. Girls also expressed less concern than boys that tanning caused
      immediate skin damage or premature aging. The pattern of correlations between the
      reasons for tanning and appearance orientation was similar for girls and boys.
      For both, appearance reasons for tanning and sociocultural influences on tanning
      were positively associated with appearance orientation. Suggestions for future
      research with adolescents and a proposal for a guiding model are provided. 

PMID- 24129216
TI  - Study of Fos, androgen receptor and testosterone expression in the sub-regions of
      medial amygdala, bed nucleus of stria terminalis and medial preoptic area in male
      Mandarin voles in response to chemosensory stimulation.
AB  - In many rodent species, including mandarin voles (Microtus mandarinus), the
      behavioral response to odors is regulated by a network of steroid-sensitive
      ventral forebrain nuclei including the medial amygdala (Me), bed nucleus of the
      striaterminalis (BNST), and medial preoptic area (MPOA). Although it is well
      known that Me, BNST, and MPOA are closely interconnected, function independently
      in regulating odor-guided social behaviors, little is known about how order
      information is processed in the sub-regions of Me, BNST, and MPOA. In order to
      answer this question, we let male mandarin voles expose to two different odors
      including female vaginal fluid (FVF) and male flank gland secretion (MFGS) and
      detect the expression of Fos, androgen receptor (AR) and testosterone (T) in the
      sub-regions of Me, BNST, and MPOA. We found that FVF stimulus caused increased
      Fos, AR and T expression in the posterior subdivision of the Me (MeP), the
      posterior medial subdivision of the BNST (BNSTpm), and the medial preoptic
      nucleus (MPN), while MFGS stimulus did not change Fos, AR and T expression
      neither in the MeP, BNSTpm, and MPN nor in the anterior subdivision of the Me
      (MeA), the posterointermediate subdivision of the BNST (BNSTpi), and the lateral
      subdivision of the MPOA (MPOAl). Serum testosterone levels were increased after
      1h in males exposed to FVF. This study provides insight in understanding the
      relationship between female odor stimulation and Fos, AR and T expression in
      specific brain areas in males, and the regulatory role of testosterone in this
      biochemical process. 

PMID- 24129217
TI  - Hypolocomotive behaviour associated with increased microglia in a prenatal immune
      activation model with relevance to schizophrenia.
AB  - Over the past decade a neurodevelopmental animal model with high validity for
      schizophrenia has been developed based on the environmental risk factor known as
      maternal immune activation (MIA). The immunological basis of this model, together
      with extensive data from clinical and preclinical context, suggests the
      involvement of an aberrant neuro-immune system in the pathophysiology of
      schizophrenia. The goal of this study was to examine microglia activation in
      adult behaviourally phenotyped MIA offspring. MIA was induced in pregnant rats
      using viral mimetic Poly I:C at gestational day 15. Adult offspring were
      behaviourally phenotyped at postnatal days (PND) 56, 90 and 180 through the
      evaluation of prepulse inhibition (PPI) of the acoustic startle and spontaneous
      locomotion. Finally, the presence of activated microglia in brain regions
      associated with schizophrenia was evaluated using post-mortem
      immunohistochemistry against OX-42 (CD11b) and ED-1 (CD68). Although a deficit in
      PPI could not be replicated despite the high number of animals tested, we found
      an overall decrease in basal startle response and spontaneous locomotion in
      offspring born to Poly I:C- compared to saline-treated dams, accompanied by
      increased microglial density with characteristics of non-reactive activation in
      the chronic stage of the model. These findings provide additional evidence for a
      role played by microglial activation in schizophrenia-related pathology in
      general and psychomotor slowing in particular, and warrant extensive research on
      the underlying mechanism in order to establish new drug targets for the treatment
      of schizophrenia patients with an inflammatory component. 

PMID- 24129218
TI  - Lessons learned from hospice care.
AB  - Pharmaceutical care of the hospice patient offers unique challenges in the
      management of pain and other symptoms. Lessons learned in providing hospice care
      can be used in the care of nonterminal patients as well to optimize patient
      specific care, regardless of care setting or life expectancy. 

PMID- 24129219
TI  - 2013-2014 ASCP President Jeffrey C. Delafuente: a passion for pharmacy.
AB  - Jeffrey C. Delafuente, MS, FCCP, FASCP, associate dean for academic affairs and
      professor of pharmacotherapy, Virginia Commonwealth University School of
      Pharmacy, Richmond, Virginia, will assume the office of 2013-2014 president of
      the American Society of Consultant Pharmacists at the Society's 2013 Annual
      Meeting & Exhibition in November. 

PMID- 24129221
TI  - Escitalopram-associated acute urinary retention.
AB  - New-onset urinary retention can typically be explained by the use of the routine
      normally suspected medications (e.g., anticholinergics, antihistamines). However,
      selective serotonin-reuptake inhibitors are not typically presumed as the cause
      of acute urinary retention (AUR). The following case describes the introduction
      of escitalopram in a patient and the subsequent development of AUR. Medical
      causes of urinary retention had been ruled out, and ipratropium was initially
      suspected to be the cause of urinary difficulties and was discontinued. However,
      the retention persisted four days after suspending the ipratropium. Normal
      micturition resumed only after stopping the escitalopram without further need for
      catheterization. Escitalopram may cause rare cases of AUR and may often times be
      overlooked possibly because of the paucity of reporting. 

PMID- 24129222
TI  - Implementing a medication safety and poison prevention program at a senior
      center.
AB  - The Institute for Safe Medication Practices encourages pharmacists to assist in
      preventing medication misuse. The purpose of this article is to discuss a
      medication-safety education session conducted by a pharmacy professor, the
      faculty advisor to the American Society of Consultant Pharmacists university
      student chapter and students in a pharmacovigilance rotation, which was conducted
      at a local senior center. The author attended a train-the-trainer Webinar and
      then educated the pharmacy students. Participants at the senior center were
      taught about poison prevention, drug interactions, and appropriate drug disposal
      through an interactive format. We plan to continue the medication safety program
      at the senior center as a longitudinal project to promote patient safety.
      Pharmacists should be encouraged to play an active role in community outreach
      programs. 

PMID- 24129223
TI  - Tapentadol-ER for the treatment of diabetic peripheral neuropathy.
AB  - With the prevalence of diabetes mellitus (DM) increasing, pathologic
      complications such as diabetic peripheral neuropathy (DPN) are also becoming more
      common. Of those diagnosed with DM, 10% to 20% of patients suffer from painful
      DPN. Until recently, only pregabalin and duloxetine possessed Food and Drug
      Administration (FDA) approval for this condition. However, FDA recently approved
      tapentadol-ER [extended release] (Nucynta ER) for painful DPN. Tapentadol-ER is
      an opioid analgesic commonly used for the treatment of moderate-to-severe chronic
      pain that contains a unique dual mechanism acting as both a weak mu-opiod
      receptor agonist and norepinephine-reuptake inhibitor. It is by way of this
      unique dual mechanism that allows for effective analgesic effects with increased
      tolerability. This new FDA approval provides an additional therapeutic option to
      treat DPN in symptomatic patients. 

PMID- 24129224
TI  - A model for the receptive field of retinal ganglion cells.
AB  - Most retina ganglion cells have center-surround receptive fields, where the
      center may be either ON or OFF while the surround is the opposite. We clarify the
      functional roles of the receptive field structure, on the basis of the modern
      theory of natural data processing. It is suggested that the retina shares the
      principal mechanism and performance of image processing with a video codec in
      computers, where the antagonism in spatial or temporal receptive fields
      originates from the orthogonality condition between linear filters for optimal
      coding of visual signals. We also reveal what visual information is multiplexed
      across the discharges of an ensemble of ganglion cells. Our theory makes it
      possible to predict the cross-correlations between ganglion cell spikes, which
      are optimized for LGN cells to respond accurately and quickly to their receptive
      fields. 

PMID- 24129225
TI  - Alterations in the expression of nNOS in the substantia nigra and subthalamic
      nucleus of 6-OHDA-lesioned rats: the effects of chronic treatment with l-DOPA and
      the nitric oxide donor, molsidomine.
AB  - Recently, it has been strongly suggested that reciprocal interactions between
      nitrergic and dopaminergic systems play a crucial role in the control of the
      nigrostriatal pathway. Degeneration of dopaminergic neurons in the substantia
      nigra (SN) in Parkinson's disease leads to disturbances in the nitrergic
      transmission in the basal ganglia. In the present study, we aimed to compare
      regional distribution of nNOS immunoreactivity and NADPH-diaphorase activity in
      the SN and subthalamic nucleus (STN) of unilaterally 6-OHDA-lesioned rats treated
      chronically with l-DOPA (25mg/kg) and the nitric oxide donor, molsidomine (2 or
      4mg/kg). Our results showed that degeneration of dopaminergic neurons in the
      ipsilateral SN resulted in a 25% decrease in the number of nNOS-immunoreactive
      neurons in that structure and in nNOS protein level determined by Western blot.
      We also found that nNOS was present in about 70% of all SN neurons. NADPH-d
      histochemistry did not reveal nNOS activity in the SN of any studied groups.
      Furthermore, the stereological analysis of the SN volume showed that chronic
      administration of l-DOPA evoked a hypertrophy of the ipsilateral SN when compared
      to the contralateral side. Such difference between sides was abolished in the
      group receiving l-DOPA in combination with molsidomine. Degeneration of the
      nigrostriatal pathway had no influence on the number of nNOS-ir neurons in the
      STN. NADPH-histochemistry revealed nNOS activity only in a part of neurons of
      that structure. Our results make an essential contribution to the research on the
      role of nitric oxide in the regulation of basal ganglia function. 

PMID- 24129226
TI  - Clinical significance of proliferative inflammatory atrophy in prostate biopsy.
AB  - INTRODUCTION: Proliferative inflammatory atrophy (PIA) is a frequently observed
      lesion in prostate biopsies and some authors have postulated its involvement in
      prostate carcinogenesis. However, the mechanisms that would permit its neoplastic
      transformation and the clinical significance of its finding in a prostate biopsy
      is currently not well known. OBJECTIVE: To analyze the characteristics of the PIA
      lesion, its possible role in prostate carcinogenesis and its relation with the
      tumor aggressiveness. MATERIAL AND METHOD: A systematic review was made of the
      literature in PubMed with the terms "proliferative inflammatory atrophy" or "PIA"
      and "prostate." The most important findings are summarized in accordance with the
      study objective. RESULTS: PIA seems to be involved in prostate carcinogenesis.
      This hypothesis is based on its frequent association to cancer lesions (CaP) and
      on some genetic alterations that are common to the high grade prostatic
      intraepithelial neoplasia (HGPIN) and to the CaP, fundamentally deficit in GSTP1
      expression and overexpression of AGR2. Currently, there are no epidemiological
      studies that evaluate the incidence of PIA or its association with HGPIN and CaP.
      Only one study, carried out by our group, has determined the global incidence of
      PIA in 30% of the prostate biopsies, a lower association to CaP than the HGPIN
      lesion and an association between PIA and tumors of lower and insignificant
      grade. CONCLUSIONS: PIA shares genetic alterations with HGPIN and CaP. Currently,
      there is no epidemiologic evidence to consider that the PIA is associated to a
      greater incidence of CaP and the genetic and epidemiological data available
      suggest its association to not very aggressive tumors.

PMID- 24129227
TI  - Parameters Affecting Image-guided, Hydrodynamic Gene Delivery to Swine Liver.
AB  - Development of a safe and effective method for gene delivery to hepatocytes is a
      critical step toward gene therapy for liver diseases. Here, we assessed the
      parameters for gene delivery to the livers of large animals (pigs, 40-65 kg)
      using an image-guided hydrodynamics-based procedure that involves image-guided
      catheter insertion into the lobular hepatic vein and hydrodynamic injection of
      reporter plasmids using a computer-controlled injector. We demonstrated that
      injection parameters (relative position of the catheter in the hepatic
      vasculature, intravascular pressure upon injection, and injection volume) are
      directly related to the safety and efficiency of the procedure. By optimizing
      these parameters, we explored for the first time, the advantage of the procedure
      for sequential injections to multiple lobes in human-sized pigs. The optimized
      procedure resulted in sustained expression of the human alpha-1 antitrypsin gene
      in livers for more than 2 months after gene delivery. In addition, repeated
      hydrodynamic gene delivery was safely conducted and no adverse events were seen
      in the entire period of the study. Our results support the clinical applicability
      of the image-guided hydrodynamic gene delivery method for the treatment of liver
      diseases.Molecular Therapy-Nucleic Acids (2013) 2, e128;
      doi:10.1038/mtna.2013.52; published online 15 October 2013. 

PMID- 24129228
TI  - Chlorella 11-peptide inhibits the production of macrophage-induced adhesion
      molecules and reduces endothelin-1 expression and endothelial permeability.
AB  - The inflammation process in large vessels involves the up-regulation of vascular
      adhesion molecules such as endothelial cell selectin (E-selectin), intercellular
      cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)
      which are also known as the markers of atherosclerosis. We have reported that
      Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide
      with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further
      examined for its potential in preventing atherosclerosis in this study. In
      particular, the roles of Chlorella 11-peptide in lowering the production of
      vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and
      expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied.
      The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was
      measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and
      agarose gel. Results showed that Chlorella 11-peptide significantly suppressed
      the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The
      inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed
      in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP
      pathway was involved in the inhibitory cause of the peptide. In addition, this
      peptide was shown to reduce the extent of increased intercellular permeability
      induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7
      cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW
      conditioned medium). These data demonstrate that Chlorella 11-peptide is a
      promising biomolecule in preventing chronic inflammatory-related vascular
      diseases. 

PMID- 24129229
TI  - Harnessing the potential of halogenated natural product biosynthesis by mangrove
      derived actinomycetes.
AB  - Mangrove-derived actinomycetes are promising sources of bioactive natural
      products. In this study, using homologous screening of the biosynthetic genes and
      anti-microorganism/tumor assaying, 163 strains of actinomycetes isolated from
      mangrove sediments were investigated for their potential to produce halogenated
      metabolites. The FADH2-dependent halogenase genes, identified in PCR-screening,
      were clustered in distinct clades in the phylogenetic analysis. The coexistence
      of either polyketide synthase (PKS) or nonribosomal peptide synthetase (NRPS) as
      the backbone synthetases in the strains harboring the halogenase indicated that
      these strains had the potential to produce structurally diversified antibiotics.
      As a validation, a new enduracidin producer, Streptomyces atrovirens MGR140, was
      identified and confirmed by gene disruption and HPLC analysis. Moreover, a
      putative ansamycin biosynthesis gene cluster was detected in Streptomyces
      albogriseolus MGR072. Our results highlight that combined genome mining is an
      efficient technique to tap promising sources of halogenated natural products
      synthesized by mangrove-derived actinomycetes. 

PMID- 24129230
TI  - Leukaemia incidence in the Techa River Cohort: 1953-2007.
AB  - BACKGROUND: Little is known about leukaemia risk following chronic radiation
      exposures at low dose rates. The Techa River Cohort of individuals residing in
      riverside villages between 1950 and 1961 when releases from the Mayak plutonium
      production complex contaminated the river allows quantification of leukaemia
      risks associated with chronic low-dose-rate internal and external exposures.
      METHODS: Excess relative risk models described the dose-response relationship
      between radiation dose on the basis of updated dose estimates and the incidence
      of haematological malignancies ascertained between 1953 and 2007 among 28 223
      cohort members, adjusted for attained age, sex, and other factors. RESULTS:
      Almost half of the 72 leukaemia cases (excluding chronic lymphocytic leukaemia
      (CLL)) were estimated to be associated with radiation exposure. These data are
      consistent with a linear dose response with no evidence of modification. The
      excess relative risk estimate was 0.22 per 100 mGy. There was no evidence of
      significant dose effect for CLL or other haematopoietic malignancies. CONCLUSION:
      These analyses demonstrate that radiation exposures, similar to those received by
      populations exposed as a consequence of nuclear accidents, are associated with
      long-term dose-related increases in leukaemia risks. Using updated dose
      estimates, the leukaemia risk per unit dose is about half of that based on
      previous dosimetry.

PMID- 24129231
TI  - Concordance of National Cancer Registration with self-reported breast, bowel and
      lung cancer in England and Wales: a prospective cohort study within the UK
      Collaborative Trial of Ovarian Cancer Screening.
AB  - BACKGROUND: It has been suggested that lower UK cancer survival may be due to
      incomplete case ascertainment by cancer registries. METHODS: We assessed
      concordance between self-reported breast, bowel and lung cancer and cancer
      registration (CR) for 1995-2007 in England and Wales in the UK Collaborative
      Trial of Ovarian Cancer Screening. RESULTS: Concordance of breast cancer CR was
      higher (94.7%:95% CI: 94.1-95.3%) than for bowel (85.1%:95% CI: 82.1-87.8%) and
      lung (85.4%:95% CI: 76.3-92.0%). CR concordance was lower in breast cancer (94.5%
      vs 98.8%) survivors compared with deceased but the difference was small. No
      difference was found for bowel (85.3% vs 94.6%) or lung (87.1% vs 90.5%) cancer.
      CONCLUSION: Concordance of CR and self-reported cancer is high. Incomplete
      registration is unlikely to be a major cause of lower UK survival rates.

PMID- 24129232
TI  - Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for
      pathological complete response to primary systemic therapy in breast cancer.
AB  - BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are known to be associated
      with response to primary systemic therapy (PST) in breast cancer. This study was
      conducted to assess the association of TIL subsets with pathological complete
      response (pCR) after PST in breast cancer in relation to breast cancer subtype,
      breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition
      (EMT). METHODS: The pre-chemotherapeutic biopsy specimens of 153 breast cancer
      patients who underwent surgical resection after anthracycline- or
      anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+
      TILs), BCSC phenotype, and the expression of EMT markers were evaluated by
      immunohistochemistry and were correlated with pCR after PST. RESULTS:
      Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC
      phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated
      with pCR, and CD8+ TILs were found to be an independent predictive factor for
      pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast
      cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in
      subgroup analyses. CONCLUSION: These findings indicate that CD8+ cytotoxic T
      lymphocytes are a key component of TILs associated with chemo-response and can be
      used as a reliable predictor of response to anthracycline- or
      anthracycline/taxane-based PST in breast cancer.

PMID- 24129233
TI  - Cost-effectiveness of sentinel lymph node biopsy vs inguinofemoral
      lymphadenectomy in women with vulval cancer.
AB  - BACKGROUND: This study examines the cost-effectiveness of sentinel lymph node
      biopsy, a potentially less morbid procedure, compared with inguinofemoral
      lymphadenectomy (IFL) among women with stage I and stage II vulval squamous cell
      carcinoma. METHODS: A model-based economic evaluation was undertaken based on
      clinical evidence from a systematic review of published sources. A decision tree
      model was developed with the structure being informed by clinical input, taking
      the perspective of the health-care provider. RESULTS: For overall survival for 2
      years, IFL was found to be the most cost-effective option and dominated all other
      strategies, being the least costly and most effective. For morbidity-free related
      outcomes for 2 years, sentinel lymph node (SLN) biopsy with 99mTc and blue dye
      and haematoxylin & eosin (H&E) histopathology, with ultrastaging and
      immunohistochemistry reserved for those that test negative following H&E is
      likely to be the most effective approach. CONCLUSION: SLN biopsy using 99mTc and
      blue dye with ultrastaging may be considered the most cost-effective strategy
      based on the outcome of survival free of morbidity for 2 years. The findings here
      also indicate that using blue dye and H&E for the identification of the SLN and
      the identification of metastasis, respectively, are not sensitive enough to be
      used on their own.

PMID- 24129234
TI  - Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma.
AB  - BACKGROUND: Aurora kinases are key regulators of cell cycle and represent new
      promising therapeutic targets in several human tumours. METHODS: Biological
      relevance of Aurora kinase-A and -B was assessed on osteosarcoma clinical samples
      and by silencing these genes with specific siRNA in three human osteosarcoma cell
      lines. In vitro efficacy of two Aurora kinases-targeting drugs (VX-680 and
      ZM447439) was evaluated on a panel of four drug-sensitive and six drug-resistant
      human osteosarcoma cell lines. RESULTS: Human osteosarcoma cell lines proved to
      be highly sensitive to both drugs. A decreased drug sensitivity was observed in
      doxorubicin-resistant cell lines, most probably related to ABCB1/MDR1
      overexpression. Both drugs variably induced hyperploidy and apoptosis in the
      majority of cell lines. VX-680 also reduced in vitro cell motility and soft-agar
      cloning efficiency. Drug association experiments showed that VX-680 positively
      interacts with all conventional drugs used in osteosarcoma chemotherapy,
      overcoming the cross-resistance observed in the single-drug treatments.
      CONCLUSION: Aurora kinase-A and -B represent new candidate therapeutic targets
      for osteosarcoma. In vitro analysis of the Aurora kinases inhibitors VX-680 and
      ZM447439 indicated in VX-680 a new promising drug of potential clinical
      usefulness in association with conventional osteosarcoma chemotherapeutic agents.

PMID- 24129235
TI  - A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the
      irinotecan in gastric carcinoma.
AB  - BACKGROUND: Cancer stem cells (CSCs) may be postulated mediators of the
      chemoresistance. This study aimed to determine an effective signal inhibitor with
      effects on the proliferation of CSCs in combination with anticancer drugs.
      METHODS: We used three gastric cancer cell lines and three side population (SP)
      enriched CSC cell lines. We examined the combined effects of inhibitors against
      stemness signals, including c-Met inhibitor SU11274, and five anticancer drugs on
      the CSC proliferation and mRNA expression of chemoresistance-associated genes.
      RESULTS: The IC50 of irinotecan in SP-enriched CSC was 10.5 times higher than
      parent OCUM-2M cells, whereas that of oxaliplatin, taxol, gemcitabine, and 5
      fluorouracil was 2.0, 2.8, 2.0, and 1.2, respectively. The SP cell lines had
      higher expression levels of UGT1A1, ABCG2, and ABCB1 than their parent cell
      lines. There was a synergistic antiproliferative effect with a combination of
      SU11274 and SN38 in SP cells, but not other inhibitors. The SU11274 significantly
      decreased the expression of UGT1A1, but not ABCG2 and ABCB1. The SN38 plus
      SU11274 group more effectively suppressed in vivo tumour growth by OCUM-2M/SP
      cells than either group alone. CONCLUSION: Cancer stem cells have chemoresistance
      to irinotecan. The c-Met inhibitor may be a promising target molecule for
      irinotecan-based chemotherapy of gastric cancer.

PMID- 24129236
TI  - Urinary tuberculosis is associated with the development of urothelial carcinoma
      but not renal cell carcinoma: a nationwide cohort study in Taiwan.
AB  - BACKGROUND: Obstructive uropathy and chronic urinary tract infection increase the
      risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic
      urinary tract inflammation, lead to obstructive uropathy, and potentially
      contribute to the development of urinary tract cancer. However, the association
      between UTB and urinary tract cancer has not been studied. METHODS: This study
      enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health
      insurance research database in Taiwan and investigated the risk factors for
      urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary
      tract cancer in the general population without TB was also calculated for
      comparison. RESULTS: The TB patients had a mean age of 57.5 +/- 19.5 years. Of
      the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed
      urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%)
      developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis
      revealed that age, male sex, end-stage renal disease, obstructive uropathy,
      arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01
      5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio
      of UTB was higher among female patients (5.26 (2.12-13.06)) than that among male
      patients (2.96 (1.57-5.60)). CONCLUSION: Urinary tuberculosis had a strong
      association with urothelial carcinoma, but not with renal cell carcinoma. In TB
      endemic areas, the urinary tract of TB patients should be scrutinised. It is also
      imperative that these patients be followed-up carefully in the post-treatment
      period, and urinalysis, ultrasonography or endoscopy should be an integral part
      of the follow-up.

PMID- 24129237
TI  - Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells
      and breast cancer cells.
AB  - BACKGROUND: Breast cancer stem cells (BCSCs) are characterized by high aldehyde
      dehydrogenase (ALDH) enzyme activity and are refractory to current treatment
      modalities, show a higher risk for metastasis, and influence the epithelial to
      mesenchymal transition (EMT), leading to a shorter time to recurrence and death.
      In this study, we focused on examination of the mechanism of action of a small
      herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the
      growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models.
      METHODS: ALDH(-) and ALDH(+) BCCs were isolated from MDA-MB-231 cells, and the
      anticancer effects of Pso were measured using cell viability, apoptosis, colony
      formation, invasion, migration, mammosphere formation, immunofluorescence, and
      western blot analysis. RESULTS: Psoralidin significantly downregulated NOTCH1
      signaling, and this downregulation resulted in growth inhibition and induction of
      apoptosis in both ALDH(-) and ALDH(+) cells. Molecularly, Pso inhibited NOTCH1
      signaling, which facilitated inhibition of EMT markers (beta-catenin and
      vimentin) and upregulated E-cadherin expression, resulting in reduced migration
      and invasion of both ALDH(-) and ALDH(+) cells. CONCLUSION: Together, our results
      suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition
      of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets
      both BCSCs and BCCs.

PMID- 24129238
TI  - Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in
      paediatric cancer and SCT.
AB  - BACKGROUND: Objectives were to describe the reliability and validity of a new
      paediatric-specific mucositis scale, the Children's International Mucositis
      Evaluation Scale (ChIMES). METHODS: In a multi-centre prospective study, children
      aged 0 to <=18 years were eligible if they were receiving any of the following:
      myeloablative stem cell transplantation (SCT), >=60 mg m(-2) course(-1)
      doxorubicin or >=12 g m(-2) methotrexate. Multiple measures of mucositis were
      included along with ChIMES. Respondents were parent proxy report for children
      aged <12 years, and child self-report for children aged 12-18 years and 8 to <12
      years. Mucositis diaries were completed at baseline and on Days 7-17 following
      chemotherapy/conditioning. On Day 14, the respondent reported presence of
      mucositis and change since the previous day. RESULTS: The 185 respondents
      included parents (N=98), children aged 12-18 years (N=66) and children aged 8 to
      <12 years (N=21). Test-retest reliability was excellent for ChIMES Total Score
      and ChIMES Percentage Score with r>0.8 for all respondent types. Criteria for
      construct validation were met across all measures. ChIMES also demonstrated
      responsiveness with significant differences between baseline and Day 14.
      CONCLUSION: ChIMES is a paediatric-specific measure of mucositis with favourable
      psychometric properties. It exhibits reliability, construct validity and
      responsiveness. ChIMES should be incorporated into clinical trials of mucositis
      prevention and treatment in paediatric cancer and SCT.

PMID- 24129239
TI  - The impact of prior platinum therapy on survival in patients with metastatic
      urothelial cancer receiving vinflunine.
AB  - BACKGROUND: A phase III trial demonstrated an overall survival advantage with the
      addition of vinflunine to best supportive care (BSC) in platinum-refractory
      advanced urothelial cancer. We subsequently examined the impact of an additional
      2 years of survival follow-up and evaluated the influence of first-line platinum
      therapy on survival. METHODS: The 357 eligible patients from the phase III study
      were categorised into two cohorts depending on prior cisplatin treatment:
      cisplatin or non-cisplatin. Survival was calculated using the Kaplan-Meier
      method. RESULTS: The majority had received prior cisplatin (70.3%). Survival was
      higher in the cisplatin group (HR: 0.76; CI 95% 0.58-0.99; P=0.04) irrespective
      of treatment arm. Multivariate analysis including known prognostic factors (liver
      involvement, haemoglobin, performance status) and prior platinum administration
      did not show an independent effect of cisplatin. Vinflunine reduced the risk of
      death by 24% in the cisplatin-group (HR: 0.76; CI 95% 0.58-0.99; P=0.04) and by
      35% in non-cisplatin patients (HR: 0.65; CI 95% 0.41-1.04; P=0.07).
      INTERPRETATION: Differences in prognostic factors between patients who can
      receive prior cisplatin and those who cannot may explain the survival differences
      in patients who undergo second line therapy. Prior cisplatin administration did
      not diminish the subsequent benefit of vinflunine over BSC.

PMID- 24129240
TI  - Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing
      sarcoma.
AB  - BACKGROUND: Though p53 mutations are rare in ES, there is a strong indication
      that p53 mutant tumours form a particularly bad prognostic group. As such, novel
      treatment strategies are warranted that would specifically target and eradicate
      tumour cells containing mutant p53 in this subset of ES patients. METHODS: PRIMA
      1(Met), also known as APR-246, is a small organic molecule that has been shown to
      restore tumour-suppressor function primarily to mutant p53 and also to induce
      cell death in various cancer types. In this study, we interrogated the ability of
      APR-246 to induce apoptosis and inhibit tumour growth in ES cells with different
      p53 mutations. RESULTS: APR-246 variably induced apoptosis, associated with Noxa,
      Puma or p21(WAF1) upregulation, in both mutant and wild-type p53 harbouring
      cells. The apoptosis-inducing capability of APR-246 was markedly reduced in ES
      cell lines transfected with p53 siRNA. Three ES cell lines established from the
      same patient at different stages of the disease and two cell lines of different
      patients with identical p53 mutations all exhibited different sensitivities to
      APR-246, indicating cellular context dependency. Comparative transcriptome
      analysis on the three cell lines established from the same patient identified
      differential expression levels of several TP53 and apoptosis-associated genes
      such as APOL6, PENK, PCDH7 and MST4 in the APR-246-sensitive cell line relative
      to the less APR-246-sensitive cell lines. CONCLUSION: This is the first study
      reporting the biological response of Ewing sarcoma cells to APR-246 exposure and
      shows gross variability in responses. Our study also proposes candidate genes
      whose expression might be associated with ES cells' sensitivity to APR-246. With
      APR-246 currently in early-phase clinical trials, our findings call for caution
      in considering it as a potential adjuvant to conventional ES-specific
      chemotherapeutics.

PMID- 24129241
TI  - CXCR3/CCR5 pathways in metastatic melanoma patients treated with adoptive therapy
      and interleukin-2.
AB  - BACKGROUND: Adoptive therapy with tumour-infiltrating lymphocytes (TILs) induces
      durable complete responses (CR) in ~20% of patients with metastatic melanoma. The
      recruitment of T cells through CXCR3/CCR5 chemokine ligands is critical for
      immune-mediated rejection. We postulated that polymorphisms and/or expression of
      CXCR3/CCR5 in TILs and the expression of their ligands in tumour influence the
      migration of TILs to tumours and tumour regression. METHODS: Tumour-infiltrating
      lymphocytes from 142 metastatic melanoma patients enrolled in adoptive therapy
      trials were genotyped for CXCR3 rs2280964 and CCR5-Delta32 deletion, which
      encodes a protein not expressed on the cell surface. Expression of CXCR3/CCR5 in
      TILs and CXCR3/CCR5 and ligand genes in 113 available parental tumours was also
      assessed. Tumour-infiltrating lymphocyte data were validated by flow cytometry
      (N=50). RESULTS: The full gene expression/polymorphism model, which includes
      CXCR3 and CCR5 expression data, CCR5-Delta32 polymorphism data and their
      interaction, was significantly associated with both CR and overall response (OR;
      P=0.0009, and P=0.007, respectively). More in detail, the predicted
      underexpression of both CXCR3 and CCR5 according to gene expression and
      polymorphism data (protein prediction model, PPM) was associated with response to
      therapy (odds ratio=6.16 and 2.32, for CR and OR, respectively). Flow cytometric
      analysis confirmed the PPM. Coordinate upregulation of CXCL9, CXCL10, CXCL11, and
      CCL5 in pretreatment tumour biopsies was associated with OR. CONCLUSION:
      Coordinate overexpression of CXCL9, CXCL10, CXCL11, and CCL5 in pretreatment
      tumours was associated with responsiveness to treatment. Conversely, CCR5-Delta32
      polymorphism and CXCR3/CCR5 underexpression influence downregulation of the
      corresponding receptors in TILs and were associated with likelihood and degree of
      response.

PMID- 24129242
TI  - MiR-221/-222 differentiate prognostic groups in advanced breast cancers and
      influence cell invasion.
AB  - BACKGROUND: MiR-221/-222 are frequently overexpressed in breast cancer and are
      associated with increased malignancy. The specific modification of microRNAs
      (miRNAs) expression could be a promising strategy in breast cancer therapy,
      leading to the suppression of tumourigenic processes in tumour cells. METHODS:
      MiR-221/-222 expressions were analysed in 86 breast cancer tissues by
      quantitative RT-PCR and tested for correlation with immunohistochemistry data and
      clinical follow-up. In vitro assays were conducted using human breast cancer cell
      lines with lentiviral overexpression of miR-221/-222. RESULTS: In tumour tissues,
      miR-221/-222 were associated with the occurrence of distant metastases. In
      particular, high levels of miR-221 were revealed to have a high prognostic impact
      for the identification of significantly different groups with advanced tumours.
      MiR-221/-222 overexpression strongly increased cell proliferation and invasion in
      vitro. Following miR-221/-222 overexpression an increased uPAR expression and
      cell invasion were observed. CONCLUSION: This study demonstrates a significant
      role for highly expressed miR-221/-222 in advanced breast cancers allowing for
      the identification of significantly different prognostic groups, particularly for
      HER2-positive and lymph-node-positive breast cancers. Considering that miR-221/
      222 are strongly involved in cell invasion, these miRNAs may be promising markers
      for breast cancer prognosis and therapy.

PMID- 24129243
TI  - Is it possible to improve the breaking bad news skills of residents when a
      relative is present? A randomised study.
AB  - BACKGROUND: Although patients with cancer are often accompanied by a relative
      during breaking bad news (BBN) consultations, little is known regarding the
      efficacy of training programmes designed to teach residents the communication
      skills needed to break bad news in a triadic consultation. METHODS: Residents
      were randomly assigned to a 40-h dyadic and triadic communication skills training
      programme (n=48) or a waiting list (n=47). A simulated BBN triadic consultation
      was audiotaped at baseline, and after training for the training group, and 8
      months after baseline for the waiting list group. Transcripts were analysed using
      content analysis software (LaComm). A coder determined the moment of bad news
      delivery and the relative's first turn of speech regarding the bad news. A
      generalised estimating equation was used to evaluate residents' communication
      skills, BBN timing, and the relative's inclusion in the consultation. RESULTS:
      Ninety-five residents were included. After training, the duration of the pre
      delivery phase was found to be longer for the trained residents (relative risk
      (RR)=3.04; P<0.001). The simulated relative's first turn of speech about the bad
      news came more often during the pre-delivery phase (RR=6.68; P=0.008), and was
      more often initiated by the trained residents (RR=19.17; P<0.001). Trained
      residents also used more assessment (RR=1.83; P<0.001) and supportive utterances
      (RR=1.58; P<0.001). CONCLUSION: This study demonstrates that a training programme
      that focuses on the practice of dyadic and triadic communication skills can
      improve the communication skills of the participating residents in a BBN triadic
      consultation. Such a training should be included in resident curriculum.

PMID- 24129244
TI  - ALK gene amplification is associated with poor prognosis in colorectal carcinoma.
AB  - BACKGROUND: Recently, the anaplastic lymphoma kinase (ALK) has been found to be
      altered in several solid and haematological tumours. ALK gene copy number changes
      and mutations in colorectal cancers (CRCs) are not well characterised. We aimed
      to study the prevalence of ALK copy number changes, translocations, gene
      mutations and protein expression in 770 CRC patients, and correlate these
      findings with molecular and clinico-pathological data. METHODS: ALK gene copy
      number variations and ALK expression were evaluated by fluorescence in situ
      hybridisation (FISH) and immunohistochemistry, respectively. RESULTS:
      Translocations of the ALK gene were not observed; 3.4% (26 out of 756) of the CRC
      patients tested had an increase in ALK gene copy number either amplification or
      gain. Interestingly, increased ALK gene copy number alteration was associated
      with poor prognosis (P=0.0135) and was an independent prognostic marker in
      multivariate Cox proportional hazards model. The study reveals a significant
      impact of ALK gene copy number alterations on the outcome of patients with CRC.
      CONCLUSION: The findings of our study highlight a potential role of targeting ALK
      in advanced CRCs by using ALK FISH and ALK IHC as a screening tool to detect ALK
      alterations. Based on these findings, a potential role of ALK inhibitor as a
      therapeutic agent in a subset of CRC merits further investigation.

PMID- 24129245
TI  - Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy
      in head and neck cancer.
AB  - BACKGROUND: We aimed to investigate the prognostic value of tumour-infiltrating
      lymphocytes' (TILs) expression in pretreatment specimens from patients with head
      and neck squamous cell carcinoma (HNSCC) treated with definitive
      chemoradiotherapy (CRT). METHODS: The prevalence of CD3+, CD8+, CD4+ and FOXP3+
      TILs was assessed using immunohistochemistry in tumour tissue obtained from 101
      patients before CRT and was correlated with clinicopathological characteristics
      as well as local failure-free- (LFFS), distant metastases free- (DMFS),
      progression-free (PFS) and overall survival (OS). Survival curves were measured
      using the Kaplan-Meier method, and differences in survival between the groups
      were estimated using the log-rank test. Prognostic effects of TIL subset density
      were determined using the Cox regression analysis. RESULTS: With a mean follow-up
      of 25 months (range, 2.3-63 months), OS at 2 years was 57.4% for the entire
      cohort. Patients with high immunohistochemical CD3 and CD8 expression had
      significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and
      DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate
      analysis that included predictive clinicopathologic factors, such as age, sex, T
      stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression
      showed significance for the clinical outcome. The lower N-stage was associated
      with improved OS in the multivariate analysis (P=0.049). CONCLUSION: The positive
      correlation between a high number of infiltrating CD3+ and CD8+ cells and
      clinical outcome indicates that TILs may have a beneficial role in HNSCC patients
      and may serve as a biomarker to identify patients likely to benefit from
      definitive CRT.

PMID- 24129246
TI  - SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53
      transcriptional activity via modulation of DBC1.
AB  - BACKGROUND: We have previously identified kinase suppressor of ras-1 (KSR1) as a
      potential regulatory gene in breast cancer. KSR1, originally described as a novel
      protein kinase, has a role in activation of mitogen-activated protein kinases.
      Emerging evidence has shown that KSR1 may have dual functions as an active kinase
      as well as a scaffold facilitating multiprotein complex assembly. Although
      efforts have been made to study the role of KSR1 in certain tumour types, its
      involvement in breast cancer remains unknown. METHODS: A quantitative mass
      spectrometry analysis using stable isotope labelling of amino acids in cell
      culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in
      breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as
      western blotting experiments were performed to further study the function of KSR1
      in breast cancer. RESULTS: Of significance, proteomic analysis reveals that KSR1
      overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation.
      Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by
      reducing the phosphorylation of DBC1, which leads to a reduced interaction of
      DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.
      CONCLUSION: Our findings integrate KSR1 into a network involving DBC1 and SIRT1,
      which results in the regulation of p53 acetylation and its transcriptional
      activity.

PMID- 24129247
TI  - MicroRNA profile: a promising ancillary tool for accurate renal cell tumour
      diagnosis.
AB  - BACKGROUND: Renal cell tumours (RCTs) are clinically, morphologically and
      genetically heterogeneous. Accurate identification of renal cell carcinomas
      (RCCs) and its discrimination from normal tissue and benign tumours is mandatory.
      We, thus, aimed to define a panel of microRNAs that might aid in the diagnostic
      workup of RCTs. METHODS: Fresh-frozen tissues from 120 RCTs (clear-cell RCC,
      papillary RCC, chromophobe RCC (chRCC) and oncocytomas: 30 cases each), 10 normal
      renal tissues and 60 cases of ex-vivo fine-needle aspiration biopsies from RCTs
      (15 of each subtype validation set) were collected. Expression levels of miR-21,
      miR-141, miR-155, miR-183 and miR-200b were assessed by quantitative reverse
      transcription-PCR. Receiver operator characteristic curves were constructed and
      the areas under the curve were calculated to assess diagnostic performance.
      Disease-specific survival curves and a Cox regression model comprising all
      significant variables were computed. RESULTS: Renal cell tumours displayed
      significantly lower expression levels of miR-21, miR-141 and miR-200b compared
      with that of normal tissues, and expression levels of all miRs differed
      significantly between malignant and benign RCTs. Expression analysis of miR-141
      or miR-200b accurately distinguished RCTs from normal renal tissues, oncocytoma
      from RCC and chRCC from oncocytoma. The diagnostic performance was confirmed in
      the validation set. Interestingly, miR-21, miR-141 and miR-155 expression levels
      showed prognostic significance in a univariate analysis. CONCLUSION: The miR-141
      or miR-200b panel accurately distinguishes RCC from normal kidney and oncocytoma
      in tissue samples, discriminating from normal kidney and oncocytoma, whereas miR
      21, miR-141 and miR-155 convey prognostic information. This approach is feasible
      in fine-needle aspiration biopsies and might provide an ancillary tool for
      routine diagnosis.

PMID- 24129249
TI  - Straightening of a corrugated extrahepatic bile duct with a fully covered self
      expandable metal stent.

PMID- 24129248
TI  - Efficacy of some synthesized thiazoles against dermatophytes.
AB  - Twelve thiazoles and their fused derivatives were tested for their antimicrobial
      activity against Trichophyton rubrum, T. terrestre, Epidermophyton floccosum, and
      Microsporum gypseum. Most of the synthesized compounds were inhibitory to the
      tested fungi. The most effective compound was 5-(4-ethoxybenzylidene-4,5-dihydro
      4-oxothiazol-2-yl)-N,3-diphenylbut-2-namide (3c) followed by 2-(4-oxo-4,5
      dihydrothiazol-2-yl)-3-phenyl-but-2-enoic acid-(3-cyano-4,5,6,7
      tetrahydrobenzo[b]thiophen-2-yl)-amide (2b). These compounds were more
      efficacious than terbinafine, the reference drug. The tested compounds caused
      variable reduction in the activity of keratinase of the dermatophytes, depending
      on the azole derivative and the test fungus. Thiazole derivatives (2b) and (3c)
      exhibited the highest efficacy in decreasing ergosterol biosynthesis of the
      tested dermatophytes. The treatment of guinea pigs with compound (3c) induced
      complete curing in the case of all the test dermatophytes 30days post-treatment.
      The percent curing for compounds (3c) and (2b) was better than the reference
      drug. 

PMID- 24129250
TI  - Endoscopic submucosal dissection through a gastrostomy for early gastric cancer
      in patients with pharyngeal stenosis.

PMID- 24129251
TI  - Unusual consequences of 'incomplete' laparoscopic cholecystectomy.
AB  - In recent years, laparoscopic cholecystectomy (LC) has become the standard
      surgical practice for the treatment of cholecystolithiasis. As a recognized
      technical difficulty, it may be associated with the mechanical injury of the
      gallbladder and/or spilling some of the gallstones into the abdominal cavity. The
      actual incidence of the latter complication is ~10%. The removal of lost stones
      from the abdominal cavity is rather elaborate if not infeasible. There is little
      information about the behaviour of retained gallstones in the free abdominal
      cavity. Publications report on subsequent intraperitoneal abscesses and fistulas
      or on the extreme localization of the impacted gallstones. This paper presents
      two cases with late complications of the abandoned gallstones or gallbladder.
      Case 1: A 56-year-old female patient underwent an LC 7 years ago. She was
      recently admitted with a chronic septic condition and suspected autoimmune
      disease. Preoperative examinations indicated hepatic abscess. Surgery showed
      gallstones impacted in the gallbladder bed. Case 2: A 59-year-old male patient
      underwent an LC a year before his admission. His operation was followed by the
      development of a septic condition and a subphrenic abscess was identified. During
      his reoperation, a remnant gallbladder containing bile stones was found and
      removed. Special attention should be paid to careful revision of residual stones
      during LC.

PMID- 24129252
TI  - Hepatitis delta virus genotype-1 alone cocirculates with hepatitis B virus
      genotypes A and D in Pakistan.
AB  - INTRODUCTION: Hepatitis delta virus (HDV) and hepatitis B virus (HBV) have been
      identified as major causes of morbidity and mortality in Pakistan because HDV
      causes infection only in the presence of HBV. Coinfection with both hepatitis
      viruses can lead to a more severe acute form of disease and to an increased risk
      of fulminant hepatitis. HDV infection differs in its distribution and severity
      depending on the geographical distribution, and several genotypes of HDV have
      been identified so far. OBJECTIVES: The aim of the present study was to establish
      the HDV and HBV genotypes in chronically infected Pakistani patients and to
      determine whether there is any correlation between HDV and HBV genotypes.
      PATIENTS AND METHODS: We studied samples from a total of 46 chronically infected
      HBV and HDV patients for HBV and HDV genotype analysis out of a total of 75
      chronic HBV carriers enrolled. HBV and HDV genotypes were determined using type
      specific PCR, followed by sequencing of PCR amplified products. RESULTS: The
      results of HBV genotyping showed that 33 of 46 (71.7%) patients had genotype D,
      five (10.9%) had A+D mixed genotypes, whereas eight (17.3) samples were
      untypable. We could detect only one HDV genotype (HDV-1) prevalent in the
      Pakistani population. The HDV-1 genotype isolate was associated with HBV genotype
      D alone or in combination with A (HBV-A+D). CONCLUSION: The present study
      concludes that HDV/HBV coinfection is very high in the Pakistani population and
      was previously underestimated. The most prevalent circulating genotypes of HBV
      and HDV are HDV-1 and HBV-D, respectively, in the studied area. There is no
      specific interaction between HBV and HDV genotypes as suggested by HDV-1/HBV-D or
      HDV-1/HBV-A+D coinfection. Coinfection of HDV-1 and HBV-D simply reflects the
      most frequent genotypes circulating in this specific geographical region of the
      world.

PMID- 24129253
TI  - Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma
      coregulation network.
AB  - Metastatic melanoma is a malignant cancer with generally poor prognosis, with no
      targeted chemotherapy. To identify epigenetic changes related to melanoma, we
      have determined genome-wide methylated CpG island distributions by next
      generation sequencing. Melanoma chromosomes tend to be differentially methylated
      over short CpG island tracts. CpG islands in the upstream regulatory regions of
      many coding and noncoding RNA genes, including, for example, TERC, which encodes
      the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated
      elements, such as LINE 2, and several LTR elements, are hypomethylated in
      advanced stage melanoma cell lines. By using CpG island demethylation profiles,
      and by integrating these data with RNA-seq data obtained from melanoma cells, we
      have identified a co-expression network of differentially methylated genes with
      significance for cancer related functions. Focused assays of melanoma patient
      tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10
      demonstrated high specificity. 

PMID- 24129254
TI  - Factor H-dependent alternative pathway inhibition mediated by porin B contributes
      to virulence of Neisseria meningitidis.
AB  - The identification of "factor H binding protein (fHbp)-null" invasive
      meningococcal isolates and the realization that widespread use of fHbp-based
      vaccines could herald selection of such strains prompted us to characterize novel
      mechanisms of alternative pathway (AP) inhibition on meningococci. Of seven
      strains engineered to lack four known AP-inhibiting molecules, capsular
      polysaccharide, lipooligosaccharide sialic acid, fHbp, and neisserial surface
      protein A (quadruple mutants), four strains inhibited human AP-mediated C3
      deposition. All four expressed the porin B2 (PorB2) molecule, and three strains
      belonged to the hypervirulent ST-11 lineage. Consistent with reduced C3
      deposition, the rate of C3a generation by a PorB2 isolate was lower than that by
      a PorB3 strain. Allelic replacement of PorB3 with PorB2, in both encapsulated and
      unencapsulated strains, confirmed the role of PorB2 in AP inhibition. Expression
      of PorB2 increased resistance to complement-dependent killing relative to that
      seen in an isogenic PorB3-expressing strain. Adult rabbit and mouse APs were
      unimpeded on all mutants, and human fH inhibited nonhuman C3 deposition on PorB2
      expressing strains, which provided functional evidence for human fH-dependent AP
      regulation by PorB2. Low-affinity binding of full-length human fH to quadruple
      mutants expressing PorB2 was demonstrated. fH-like protein 1 (FHL-1; contains fH
      domains 1 through 7) and fH domains 6 and 7 fused to IgG Fc bound to one PorB2
      expressing quadruple mutant, which suggested that fH domains 6 and 7 may interact
      with PorB2. These results associate PorB2 expression with serum resistance and
      presage the appearance of fHbp-null and hypervirulent ST-11 isolates that may
      evade killing by fHbp-based vaccines. IMPORTANCE: The widespread use of
      antimeningococcal vaccines based on factor H (fH) binding protein (fHbp) is
      imminent. Meningococci that lack fHbp were recently isolated from persons with
      invasive disease, and these fHbp-null strains could spawn vaccine failure. Our
      report provides a molecular basis for an explanation of how fHbp-null strains may
      evade the host immune system. Meningococci possess several mechanisms to subvert
      killing by the alternative pathway (AP) of complement, including production of
      the fHbp and NspA fH binding proteins. Here we show that a meningococcal protein
      called porin B2 (PorB2) contributes to inhibition of the AP on the bacterial
      surface. A majority of the "fHbp-null" isolates identified, as well as all
      members of a "hypervirulent" lineage (called ST-11), express PorB2. Our findings
      highlight the potential for the emergence of fHbp-negative strains that are able
      to regulate the AP and may be associated with fHbp vaccine failure.

PMID- 24129255
TI  - The general phosphotransferase system proteins localize to sites of strong
      negative curvature in bacterial cells.
AB  - The bacterial cell poles are emerging as subdomains where many cellular
      activities take place, but the mechanisms for polar localization are just
      beginning to unravel. The general phosphotransferase system (PTS) proteins,
      enzyme I (EI) and HPr, which control preferential use of carbon sources in
      bacteria, were recently shown to localize near the Escherichia coli cell poles.
      Here, we show that EI localization does not depend on known polar constituents,
      such as anionic lipids or the chemotaxis receptors, and on the cell division
      machinery, nor can it be explained by nucleoid occlusion or localized
      translation. Detection of the general PTS proteins at the budding sites of
      endocytotic-like membrane invaginations in spherical cells and their
      colocalization with the negative curvature sensor protein DivIVA suggest that
      geometric cues underlie localization of the PTS system. Notably, the kinetics of
      glucose uptake by spherical and rod-shaped E. coli cells are comparable, implying
      that negatively curved "pole-like" sites support not only the localization but
      also the proper functioning of the PTS system in cells with different shapes.
      Consistent with the curvature-mediated localization model, we observed the EI
      protein from Bacillus subtilis at strongly curved sites in both B. subtilis and
      E. coli. Taken together, we propose that changes in cell architecture correlate
      with dynamic survival strategies that localize central metabolic systems like the
      PTS to subcellular domains where they remain active, thus maintaining cell
      viability and metabolic alertness. IMPORTANCE: Despite their tiny size and the
      scarcity of membrane-bounded organelles, bacteria are capable of sorting
      macromolecules to distinct subcellular domains, thus optimizing functionality of
      vital processes. Understanding the cues that organize bacterial cells should
      provide novel insights into the complex organization of higher organisms.
      Previously, we have shown that the general proteins of the phosphotransferase
      system (PTS) signaling system, which governs utilization of carbon sources in
      bacteria, localize to the poles of Escherichia coli cells. Here, we show that
      geometric cues, i.e., strong negative membrane curvature, mediate positioning of
      the PTS proteins. Furthermore, localization to negatively curved regions seems to
      support the PTS functionality.

PMID- 24129256
TI  - A distinguishable role of eDNA in the viscoelastic relaxation of biofilms.
AB  - Bacteria in the biofilm mode of growth are protected against chemical and
      mechanical stresses. Biofilms are composed, for the most part, of extracellular
      polymeric substances (EPSs). The extracellular matrix is composed of different
      chemical constituents, such as proteins, polysaccharides, and extracellular DNA
      (eDNA). Here we aimed to identify the roles of different matrix constituents in
      the viscoelastic response of biofilms. Staphylococcus aureus, Staphylococcus
      epidermidis, Streptococcus mutans, and Pseudomonas aeruginosa biofilms were grown
      under different conditions yielding distinct matrix chemistries. Next, biofilms
      were subjected to mechanical deformation and stress relaxation was monitored over
      time. A Maxwell model possessing an average of four elements for an individual
      biofilm was used to fit the data. Maxwell elements were defined by a relaxation
      time constant and their relative importance. Relaxation time constants varied
      widely over the 104 biofilms included and were divided into seven ranges (<1, 1
      to 5, 5 to 10, 10 to 50, 50 to 100, 100 to 500, and >500 s). Principal-component
      analysis was carried out to eliminate related time constant ranges, yielding
      three principal components that could be related to the known matrix chemistries.
      The fastest relaxation component (<3 s) was due to the presence of water and
      soluble polysaccharides, combined with the absence of bacteria, i.e., the
      heaviest masses in a biofilm. An intermediate component (3 to 70 s) was related
      to other EPSs, while a distinguishable role was assigned to intact eDNA, which
      possesses a unique principal component with a time constant range (10 to 25 s)
      between those of EPS constituents. This implies that eDNA modulates its
      interaction with other matrix constituents to control its contribution to
      viscoelastic relaxation under mechanical stress. IMPORTANCE: The protection
      offered by biofilms to organisms that inhabit it against chemical and mechanical
      stresses is due in part to its matrix of extracellular polymeric substances
      (EPSs) in which biofilm organisms embed themselves. Mechanical stresses lead to
      deformation and possible detachment of biofilm organisms, and hence,
      rearrangement processes occur in a biofilm to relieve it from these stresses.
      Maxwell analysis of stress relaxation allows the determination of characteristic
      relaxation time constants, but the biofilm components and matrix constituents
      associated with different stress relaxation processes have never been identified.
      Here we grew biofilms with different matrix constituents and used principal
      component analysis to reveal that the presence of water and soluble
      polysaccharides, together with the absence of bacteria, is associated with the
      fastest relaxation, while other EPSs control a second, slower relaxation.
      Extracellular DNA, as a matrix constituent, had a distinguishable role with its
      own unique principal component in stress relaxation with a time constant range
      between those of other EPSs.

PMID- 24129257
TI  - Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus
      strains in the United States.
AB  - Coronaviruses are known to infect humans and other animals and cause respiratory
      and gastrointestinal diseases. Here we report the emergence of porcine epidemic
      diarrhea virus (PEDV) in the United States and determination of its origin,
      evolution, and genotypes based on temporal and geographical evidence.
      Histological lesions in small intestine sections of affected pigs and the
      complete genomic sequences of three emergent strains of PEDV isolated from
      outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic
      analyses of the three U.S. strains revealed a close relationship with Chinese
      PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent
      evolutionary divergence, which can be classified into two sublineages. The three
      emergent U.S. strains are most closely related to a strain isolated in 2012 from
      Anhui Province in China, which might be the result of multiple recombination
      events between different genetic lineages or sublineages of PEDV. Molecular clock
      analysis of the divergent time based on the complete genomic sequences is
      consistent with the actual time difference, approximately 2 to 3 years, of the
      PED outbreaks between China (December 2010) and the United States (May 2013). The
      finding that the emergent U.S. PEDV strains share unique genetic features at the
      5'-untranslated region with a bat coronavirus provided further support of the
      evolutionary origin of PEDV from bats and potential cross-species transmission.
      The data from this study have important implications for understanding the
      ongoing PEDV outbreaks in the United States and will guide future efforts to
      develop effective preventive and control measures against PEDV. IMPORTANCE: The
      sudden emergence of porcine epidemic diarrhea virus (PEDV), a coronavirus, for
      the first time in the United States causes significant economic and public health
      concerns. Since its recognition in May 2013, PEDV has rapidly spread across the
      United States, resulting in high mortality in piglets in more than 17 States now.
      The ongoing outbreaks of Middle East respiratory syndrome coronavirus in humans
      from countries in or near the Arabian Peninsula and the historical deadly nature
      of the 2002 outbreaks of severe acute respiratory syndrome coronavirus create
      further anxiety over the emergence of PEDV in the United States due to the lack
      of scientific information about the origin and evolution of this emerging
      coronavirus. Here we report the detailed genetic characterization, origin, and
      evolution of emergent PEDV strains in the United States. The results provide much
      needed information to devise effective preventive and control strategies against
      PEDV in the United States.

PMID- 24129258
TI  - Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial,
      and associated with reduced invasiveness and immunoreactivity during
      colonization.
AB  - Biofilms are thought to play an important role during colonization of the
      nasopharynx by Streptococcus pneumoniae, yet how they form in vivo and the
      determinants responsible remain unknown. Using scanning electron microscopy, we
      show that biofilm aggregates of increasing complexity form on murine nasal septa
      following intranasal inoculation. These biofilms were highly distinct from in
      vitro biofilms, as they were discontiguous and appeared to incorporate
      nonbacterial components such as intact host cells. Biofilms initially formed on
      the surface of ciliated epithelial cells and, as cells were sloughed off, were
      found on the basement membrane. The size and number of biofilm aggregates within
      nasal lavage fluid were digitally quantitated and revealed strain-specific
      capabilities that loosely correlated with the ability to form robust in vitro
      biofilms. We tested the ability of isogenic mutants deficient in CbpA,
      pneumolysin, hydrogen peroxide, LytA, LuxS, CiaR/H, and PsrP to form biofilms
      within the nasopharynx. This analysis revealed that CiaR/H was absolutely
      required for colonization, that PsrP and SpxB strongly impacted aggregate
      formation, and that other determinants affected aggregate morphology in a modest
      fashion. We determined that mice colonized with DeltapsrP mutants had greater
      levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha),
      interleukin-6 (IL-6), IL-1beta, and KC in nasal lavage fluid than did mice
      colonized with wild-type controls. This phenotype correlated with a diminished
      capacity of biofilm pneumococci to invade host cells in vitro despite enhanced
      attachment. Our results show that biofilms form during colonization and suggest
      that they may contribute to persistence through a hyperadhesive, noninvasive
      state that elicits a dampened cytokine response. IMPORTANCE: This work
      demonstrates the first temporal characterization of Streptococcus pneumoniae
      biofilm formation in vivo. Our results show that the morphology of biofilms
      formed by both invasive and noninvasive clinical isolates in vivo is distinct
      from that of formed biofilms in vitro, yet propensity to form biofilms in vivo
      loosely correlates with the degree of in vitro biofilm formation on a microtiter
      plate. We show that host components, including intact host cells, influence the
      formation of in vivo structures. We also found that efficient biofilm formation
      in vivo requires multiple bacterial determinants. While some factors are
      essential for in vivo biofilm formation (CiaRH, PsrP, and SpxB), other factors
      are less critical (CbpA, LytA, LuxS, and pneumolysin). In comparison to their
      planktonic counterparts, biofilm pneumococci are hyperadhesive but less invasive
      and elicit a weaker proinflammatory cytokine response. These findings give
      insight into the requirements for and potential role of biofilms during prolonged
      asymptomatic colonization.

PMID- 24129259
TI  - Toward identification of the genetic risk profile for cryptococcal disease in HIV
      infected patients.
AB  - Cryptococcus spp. are important fungal pathogens that represent a major cause of
      morbidity and mortality in both immunocompetent and immunodeficient patients.
      Although cryptococcal disease is one of the major causes of death in HIV-infected
      patients, especially in sub-Saharan Africa, not all patients at risk with low CD4
      counts develop the disease. It has been thus hypothesized that host genetic
      variation may represent an important susceptibility risk factor for this
      infection. In their recent study in mBio, Rohatgi et al. [S. Rohatgi et al., mBio
      4(5):e00573-13, 2013, doi:10.1128/mBio.00573-13] present an important piece of
      evidence to support this hypothesis, by demonstrating that the FCGR3A 158 F/V
      polymorphism has an important impact on susceptibility to cryptococcal disease in
      HIV-infected patients. The authors present both genetic evidence and
      immunological validation for the hypothesis that humoral immunity in general and
      FCGR3A-mediated uptake and antibody-dependent cellular cytotoxicity (ADCC) in
      particular play important roles in the pathogenesis of Cryptococcus infection.
      Their discovery that the 158V allele of this polymorphism can increase the risk
      of Cryptococcus infections up to 20-fold in homozygous individuals opens the
      possibility for risk stratification and personalized treatment of HIV-infected
      patients.

PMID- 24129260
TI  - Clinical practice guidelines for healthy eating for the prevention and treatment
      of metabolic and endocrine diseases in adults: cosponsored by the American
      Association of Clinical Endocrinologists/the American College of Endocrinology
      and the Obesity Society.

PMID- 24129261
TI  - Valence band offset, strain and shape effects on confined states in self
      assembled InAs/InP and InAs/GaAs quantum dots.
AB  - I present a systematic study of self-assembled InAs/InP and InAs/GaAs quantum dot
      single-particle and many-body properties as a function of the quantum dot
      surrounding matrix valence band offset. I use an atomistic, empirical tight
      binding approach and perform numerically demanding calculations for half-million
      atom nanosystems. I demonstrate that the overall confinement in quantum dots is a
      non-trivial interplay of two key factors: strain effects and the valence band
      offset. I show that strain effects determine both the peculiar structure of
      confined hole states of lens type InAs/GaAs quantum dots and the characteristic
      'shell-like' structure of confined hole states in the commonly considered 'low
      strain' lens type InAs/InP quantum dot. I also demonstrate that strain leads to
      single-band-like behavior of hole states of disk type ('indium flushed')
      InAs/GaAs and InAs/InP quantum dots. I show how strain and valence band offset
      affect quantum dot many-body properties: the excitonic fine structure, an
      important factor for efficient entangled photon pair generation, and the
      biexciton and charged exciton binding energies. 

PMID- 24129262
TI  - Amino acids as biomarkers in the SOD1(G93A) mouse model of ALS.
AB  - The development of therapies for Amyotrophic Lateral Sclerosis (ALS) has been
      hindered by the lack of biomarkers for both identifying early disease and for
      monitoring the effectiveness of drugs. The identification of ALS biomarkers in
      presymptomatic individuals might also provide clues to the earliest biochemical
      correlates of the disease. Previous attempts to use plasma metabolites as
      biomarkers have led to contradictory results, presumably because of heterogeneity
      in both the underlying genetics and the disease stage in the clinical population.
      To eliminate these two sources of heterogeneity we have characterized plasma
      amino acids and other metabolites in the SOD1(G93A) transgenic mouse model for
      ALS. Presymptomatic SOD1(G93A) mice have significant differences in
      concentrations of several plasma metabolites compared to wild type animals, most
      notably in the concentrations of aspartate, cystine/cysteine, and
      phosphoethanolamine, and in changes indicative of methylation defects. There are
      significant changes in amino acid compositions between 50 and 70days of age in
      both the SOD1(G93A) and wild type mice, and several of the age-related and
      disease-related differences in metabolite concentration were also gender
      specific. Many of the SOD1(G93A)-related differences could be altered by
      treatment of mice with methionine sulfoximine, which extends the lifespan of this
      mouse, inhibits glutamine synthetase, and modifies brain methylation reactions.
      These studies show that assaying plasma metabolites can effectively distinguish
      transgenic mice from wild type, suggesting that one or more plasma metabolites
      might be useful biomarkers for the disease in humans, especially if genetic and
      longitudinal analysis is used to reduce population heterogeneity. 

PMID- 24129264
TI  - Effectiveness of school-based smoking intervention in middle school students of
      Linzhi Tibetan and Guangzhou Han ethnicity in China.
AB  - PURPOSE: The purpose of this paper is to assess the effectiveness of school-based
      intervention aimed to increase knowledge, to change attitudes and to reduce
      smoking-related behavior in both Linzhi Tibetan and Guangzhou Han middle school
      students in China. DESIGN: A concurrent intervention study was conducted in both
      Linzhi and Guangzhou. Two schools were randomly chosen and one was randomly
      assigned to the intervention group and the other to the control group in both
      settings. SETTING/PARTICIPANTS: Participants were grade one and grade two middle
      school students drawn from two schools in Linzhi, Tibet Autonomous Region
      (southwest China) and two schools in Guangzhou, Guangdong Province (south China).
      INTERVENTION: The intervention program lasted for one year and covered three
      aspects: health policies in school, health environment in school and personal
      health skills. MAIN OUTCOME MEASURES: Primary outcomes were smoking-related
      knowledge, attitudes and behavior (including ever smoking, daily smoking, weekly
      smoking and current smoking) and were measured by a self-administered
      questionnaire before and after the intervention. RESULTS: This intervention
      increased smoking-related knowledge in both Tibetan (beta=1.32, 95% CI (0.87
      1.77)) and Han ethnic groups (beta=0.47, 95% CI (0.11-0.83)). It changed
      attitudes toward smoking in Tibetan (beta=1.47, 95% CI (0.06-2.87)) but not so in
      Han (beta=-0.33, 95% CI (-1.68-1.01)). The intervention changed the prevalence of
      smoking in neither ethnic groups (P>0.05). CONCLUSIONS: The impact of school
      based smoking intervention is different among Tibetan and Han students. This
      intervention was more effective for Tibetans when compared with the Han ethnic
      group. More research is needed on how intervention can be adapted to address
      ethnic and cultural differences.

PMID- 24129263
TI  - The oxytocin analogue carbetocin prevents emotional impairment and stress-induced
      reinstatement of opioid-seeking in morphine-abstinent mice.
AB  - The main challenge in treating opioid addicts is to maintain abstinence due to
      the affective consequences associated with withdrawal which may trigger relapse.
      Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT)
      in the modulation of mood disorders as well as drug addiction. However, its
      involvement in the emotional consequences of drug abstinence remains unclear. We
      investigated the effect of 7-day opioid abstinence on the oxytocinergic system
      and assessed the effect of the OT analogue carbetocin (CBT) on the emotional
      consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were
      treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.).
      Seven days withdrawal from this administration paradigm induced a decrease of
      hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR)
      binding in the lateral septum and amygdala. Although no physical withdrawal
      symptoms or alterations in the plasma corticosterone levels were observed after 7
      days of abstinence, mice exhibited increased anxiety-like and depressive-like
      behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed
      negative emotional consequences of opioid withdrawal. Furthermore, in the
      conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT
      (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to
      morphine-seeking following extinction. Overall, our results suggest that
      alterations of the oxytocinergic system contribute to the mechanisms underlying
      anxiety, depression, and social deficits observed during opioid abstinence. This
      study also highlights the oxytocinergic system as a target for developing
      pharmacotherapy for the treatment of emotional impairment associated with
      abstinence and thereby prevention of relapse.

PMID- 24129265
TI  - Alcohol intoxication and condom use self-efficacy effects on women's condom use
      intentions.
AB  - Although research has consistently demonstrated that condom use self-efficacy
      significantly predicts condom use, there has been little investigation of whether
      acute alcohol intoxication moderates this relationship. Because alcohol
      intoxication is often associated with increased sexual risk taking, further
      examination of such moderating effects is warranted. Using a community sample of
      young heterosexual women (n=436) with a history of heavy episodic drinking, this
      alcohol administration experiment examined the effects of intoxication and condom
      use self-efficacy on women's condom negotiation and future condom use intentions.
      After a questionnaire session, alcohol condition (control, .10% target peak BAL)
      was experimentally manipulated between subjects. Participants then read and
      responded to a hypothetical risky sexual decision-making scenario. SEM analyses
      revealed that alcohol intoxication directly decreased women's intentions to use
      condoms in the future. Women with greater condom use self-efficacy had stronger
      intentions to engage in condom negotiation; however, this effect was moderated by
      intoxication. Specifically, the association between condom use self-efficacy and
      condom negotiation intentions was stronger for intoxicated women than for sober
      women. These novel findings regarding the synergistic effects of alcohol
      intoxication and condom use self-efficacy support continued prevention efforts
      aimed at strengthening women's condom use self-efficacy, which may reduce even
      those sexual risk decisions made during states of intoxication. 

PMID- 24129266
TI  - Letter to the editor: "The origin of free glutamate in milk: a role for anionic
      amino acid transporters".

PMID- 24129267
TI  - Reply to "Letter to the editor: 'The origin of free glutamate in milk: a role for
      anionic amino acid transporters'".

PMID- 24129268
TI  - The Type 1 secretion pathway - the hemolysin system and beyond.
AB  - Type 1 secretion systems (T1SS) are wide-spread among Gram-negative bacteria. An
      important example is the secretion of the hemolytic toxin HlyA from uropathogenic
      strains. Secretion is achieved in a single step directly from the cytosol to the
      extracellular space. The translocation machinery is composed of three
      indispensable membrane proteins, two in the inner membrane, and the third in the
      outer membrane. The inner membrane proteins belong to the ABC transporter and
      membrane fusion protein families (MFPs), respectively, while the outer membrane
      component is a porin-like protein. Assembly of the three proteins is triggered by
      accumulation of the transport substrate (HlyA) in the cytoplasm, to form a
      continuous channel from the inner membrane, bridging the periplasm and finally to
      the exterior. Interestingly, the majority of substrates of T1SS contain all the
      information necessary for targeting the polypeptide to the translocation channel 
      a specific sequence at the extreme C-terminus. Here, we summarize our current
      knowledge of regulation, channel assembly, translocation of substrates, and in
      the case of the HlyA toxin, its interaction with host membranes. We try to
      provide a complete picture of structure function of the components of the
      translocation channel and their interaction with the substrate. Although we will
      place the emphasis on the paradigm of Type 1 secretion systems, the hemolysin A
      secretion machinery from E. coli, we also cover as completely as possible current
      knowledge of other examples of these fascinating translocation systems. This
      article is part of a Special Issue entitled: Protein trafficking and secretion in
      bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. 

PMID- 24129269
TI  - Preserved echinoderm gametes as a useful and ready-to-use bioassay material.
AB  - Marine animals, and sea urchin species in particular, have several advantages for
      use in environmental research. However, the spawned eggs of the sea urchin
      quickly lose fertility, although the fertile period can be lengthened by the
      addition of antibiotics to the sea water (Epel et al., 2004). We evaluated five
      species of Japanese sea urchin and the gametes of Hemicentrotus pulcherrimus
      could be maintained for 2 weeks or more at low temperature with the addition of
      antibiotics to sea water. We also demonstrated the practicality of shipping these
      preserved gametes as experimental material for universities and schools to use
      immediately for bioassays of physical and chemical impacts on the marine
      environment. 

PMID- 24129270
TI  - INSEL: an in silico method for optimizing and exploring biorecognition assays.
AB  - A practical in silico method for optimizing and exploring biointeraction-based
      events is developed. 

PMID- 24129271
TI  - Objective concussion assessment in athletics and diffusion tensor imaging.

PMID- 24129272
TI  - Diffusion tensor imaging in the spotlight on concussion.

PMID- 24129273
TI  - The utility of modified recursive partitioning analysis class 2 in predicting
      survival among surgical candidates with intracranial metastases.

PMID- 24129274
TI  - Structural studies and investigation on the activity of imidazole-derived
      thiosemicarbazones and hydrazones against crop-related fungi.
AB  - New imidazole derived thiosemicarbazones and hydrazones were prepared by
      condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde
      and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All
      compounds were characterized by quantitative elemental analysis, IR and NMR
      techniques. Eight structures were determined by single crystal X-ray diffraction.
      The antifungal activities of the compounds were evaluated. None of the compounds
      exhibited significant activity against Aspergillus flavus and Candida albicans,
      while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1
      yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active
      against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl
      hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone
      (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone
      (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone
      (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone
      (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and
      4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases,
      activity was superior to that of the reference compound nystatin. 

PMID- 24129275
TI  - Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as
      antioxidants.
AB  - An antioxidant mechanism of tetrahydrocannabinol (THC) and cannabidiol (CBD) were
      compared with a simplified model of alpha-tocopherol, butylhydroxytoluene and
      hydroxytoluene in order to understand the antioxidant nature of THC and CBD
      molecules using DFT. The following electronic properties were evaluated: frontier
      orbitals nature, ionization potential, O-H bond dissociation energy (BDEOH),
      stabilization energy, and spin density distribution. An important factor that
      shows an influence in the antioxidant property of THC is the electron abstraction
      at the phenol position. Our data indicate that the decrease of the HOMO values
      and the highest ionization potential values are related to phenol, ether, and
      alkyl moieties. On the other hand, BDEOH in molecules with the cyclohexenyl group
      at ortho position of phenol are formed from lower energies than the molecules
      with an ether group at the meta position. In the light of our results, the
      properties calculated here predict that THC has a sightly higher antioxidant
      potential than CBD. 

PMID- 24129276
TI  - Electrochemical enzyme-linked immunosorbent assay (ELISA) for alpha-fetoprotein
      based on glucose detection with multienzyme-nanoparticle amplification.
AB  - Since glucose biosensors are one of the most popular and widely used point-of
      care testing devices, a novel electrochemical enzyme-linked immunosorbent assay
      (ELISA) for protein biomarkers has been developed based on a glucose detection
      strategy. In this study, alpha-fetoprotein (AFP) was used as the target protein.
      An electrochemical ELISA system was constructed using anti-AFP antibodies
      immobilized on microwell plates as the capture antibody (Ab1) and multi-label
      bioconjugates as signal tracer. The bioconjugates were synthesized by attaching
      glucoamylase and the secondary anti-AFP antibodies (Ab2) to gold nanoparticles
      (AuNPs). After formation of the sandwich complex, the Ab2-glucoamylase-AuNPs
      conjugates converted starch into glucose in the presence of AFP. The
      concentration of AFP can be calculated based on the linear relation between AFP
      and glucose, the concentration of which can be detected by the glucose biosensor.
      When the AFP concentration ranged from 0.05 to 100 ng/mL, a linear calibration
      plot (i (uA) = 13.62033 - 2.86252 logCAFP (ng/mL), r = 0.99886) with a detection
      limit of 0.02 ng/mL was obtained under optimal conditions. The electrochemical
      ELISA developed in this work shows acceptable stability and reproducibility, and
      the assay for AFP spiked in human serum also shows good recovery (97.0%-104%).
      This new method could be applied for detecting any protein biomarker with the
      corresponding antibodies. 

PMID- 24129277
TI  - Orbital interaction and electron density transfer in PdII([9]aneB2A)L2 complexes:
      theoretical approaches.
AB  - The geometric structures of Pd-complexes {Pd([9]aneB2A)L2 and Pd([9]aneBAB)L2
      where A = P, S; B = N; L = PH3, P(CH3)3, Cl-}, their selective orbital
      interaction towards equatorial or axial (soft A...Pd) coordination of macrocyclic
      [9]aneB2A tridentate to PdL2, and electron density transfer from the electron
      rich trans L-ligand to the low-lying unfilled a1g(5s)-orbital of PdL2 were
      investigated using B3P86/lanl2DZ for Pd and 6-311+G** for other atoms. The
      pentacoordinate endo-[Pd([9]aneB2A)(L-donor)2]2+ complex with an axial (soft A-
      Pd) quasi-bond was optimized for stability. The fifth (soft A--Pd) quasi-bond
      between the sigma-donor of soft A and the partially unfilled a1g(5s)-orbital of
      PdL2 was formed. The pentacoordinate endo-Pd([9]aneB2A)(L-donor)2]2+ complex has
      been found to be more stable than the corresponding tetracoordinate endo-Pd
      complexes. Except for the endo-Pd pentacoordinates, the tetracoordinate
      Pd([9]aneBAB)L2 complex with one equatorial (soft A-Pd) bond is found to be more
      stable than the Pd([9]aneB2A)L2 isomer without the equatorial (A-Pd) bond. In
      particular, the geometric configuration of endo-[Pd([9]anePNP)(L-donor)2]2+ could
      not be optimized. 

PMID- 24129278
TI  - Tuberculosis and leprosy in Italy: new skeletal evidence.
AB  - Tuberculosis (TB) and leprosy are infections caused by Mycobacteria. This paper
      documents new skeletal evidence in Italy from the Iron Age site of Corvaro
      (Central Italy; 5th century BCE) and the Roman site of Palombara (Central Italy;
      4th-5th century CE), and briefly reviews the extant evidence for these infections
      in Italy. The skeletal evidence for TB in Italy is more ancient than for leprosy,
      and is more common. The oldest evidence for both mycobacterial diseases is in the
      North of Italy, but this could be by chance, even if biomolecular models suggest
      a land route from the East to central Europe, especially for leprosy. 

PMID- 24129279
TI  - [Prevalence and risk factors of urinary incontinence in women who visit the
      doctor with low back pain: multicentre study].
AB  - OBJECTIVES: Estimating prevalence and risk factors of urinary incontinence (UI)
      in women with low back pain (LBP) and describing their social and demographic and
      clinical features. DESIGN: Cross-sectional study. SETTING: Two primary care
      health centres in south of Cordoba and a private center in Madrid. PARTICIPANTS:
      364 women of 20-65 years of age (of 466 who were contacted, 33 of them were
      excluded and 69 refused to participate) who had low back pain located between the
      twelfth rib and the gluteal fold. INTERVENTIONS: Medical questionnaire. MAIN
      MEASUREMENTS: Questionnaires (Oswestry Disability Index and UI questionnaires
      [International Consultation on Incontinence Questionnaire SF and Incontinence
      Impact Questionnaire-7]), functional test (ASLR Test) and comorbidity of interest
      for the UI. Descriptive and multivariate statistical analysis. RESULTS: UI was
      detected in 155 women (43%, 95% CI: 37%-48%), the majority of stress (83%) and a
      minimal impact (60%). Front of the continents, incontinent women showed
      significant differences in age, body mass index, marital status, level of
      education, coexistence, consumption of drugs/day, number of vaginal and total
      deliveries, abdominal and pelvic surgery, asthma, constipation, hypertension,
      diabetes, percentage of disability and functional ASLR test. In multivariate
      analysis, the variables influencing the probability of being incontinent were
      asthma, hypertension, constipation, total parity, BMI and the percentage of
      disability. CONCLUSIONS: Prevalence of UI is higher than in women without low
      back pain. Asthma, constipation and parity are the most influential factors in
      the occurrence of UI.

PMID- 24129280
TI  - [How is HIV disease cared for in a Department of Health?].

PMID- 24129281
TI  - [Usefulness of ultrasound in benign prostate hypertrophy in primary care].

PMID- 24129282
TI  - Antimicrobial stewardship programs: a public health priority in Spain. The SEIMC
      REIPI initiative.

PMID- 24129283
TI  - Inappropriate use of antibiotics in hospitals: the complex relationship between
      antibiotic use and antimicrobial resistance.
AB  - Hospitals are considered an excellent compartment for the selection of resistant
      and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial
      agents are considered key points fuelling this situation. Antimicrobial
      stewardship programs have been designed for better use of these compounds to
      prevent the emergence of resistant microorganisms and to diminish the upward
      trend in resistance. Nevertheless, the relationship between antibiotic use and
      antimicrobial resistance is complex, and the desired objectives are difficult to
      reach. Various factors affecting this relationship have been advocated including,
      among others, antibiotic exposure and mutant selection windows, antimicrobial
      pharmacodynamics, the nature of the resistance (natural or acquired, including
      mutational and that associated with horizontal gene transfer) and the definition
      of resistance. Moreover, antimicrobial policies to promote better use of these
      drugs should be implemented not only in the hospital setting coupled with
      infection control programs, but also in the community, which should also include
      animal and environmental compartments. Within hospitals, the restriction of
      antimicrobials, cycling and mixing strategies and the use of combination
      therapies have been used to avoid resistance. Nevertheless, the results have not
      always been favorable and resistant bacteria have persisted despite the
      theoretical benefits of these strategies. Mathematical models as well as
      microbiological knowledge can explain this failure, which is mainly related to
      the current scenario involving MDR bacteria and overcoming the fitness associated
      with resistance. New antimicrobials, rapid diagnostic and antimicrobial
      susceptibility testing and biomarkers will be useful for future antimicrobial
      stewardship interventions. 

PMID- 24129284
TI  - A review of the factors influencing antimicrobial prescribing.
AB  - There are multiple benefits of appropriate antimicrobial prescribing: it has a
      direct impact on clinical outcomes, avoids adverse effects, is cost effective
      and, perhaps most importantly, it helps to prevent the emergence of resistance.
      However, any physician can prescribe antibiotics, which is not the case with
      other clinically relevant drugs. There is great variability in the prescribing
      physician's (PP) training, motivation, workload and setting, including
      accessibility to infectious diseases consultants and/or diagnostic techniques,
      and therefore there is a high risk of inappropriate prescription. Many antibiotic
      prescribing errors occur around the selection and duration of treatment. This
      includes a low threshold for the indication of antibiotics, delayed initiation of
      treatment when indicated, limited knowledge of local antimicrobial resistance
      patterns by the PPs, errors in the final choice of dose, route or drug and a lack
      of de-escalation. Similarly, the prescription of prophylactic antibiotics to
      prevent surgical site infections, despite being commonly accepted, is suboptimal.
      Factors that may explain suboptimal use are related to the absence of well
      defined protocols, poor knowledge of prophylactic protocols, miscommunication or
      disagreement between physicians, logistical problems, and a lack of audits. A
      proper understanding of the prescribing process can guide interventions to
      improve the PP's practices. Some of the potential interventions included in a
      stewardship program are education in antimicrobial prescribing, information on
      the local resistance patterns and accessibility to a qualified infectious
      diseases consultant. 

PMID- 24129285
TI  - How to measure and monitor antimicrobial consumption and resistance.
AB  - Collateral damage caused by antibiotic use includes resistance, which could be
      reduced if the global inappropriate use of antibiotics, especially in low-income
      countries, could be prevented. Surveillance of antimicrobial consumption can
      identify and target practice areas for quality improvement, both in the community
      and in healthcare institutions. The defined daily dose, the usual adult dose of
      an antimicrobial for treating one patient for one day, has been considered useful
      for measuring antimicrobial prescribing trends within a hospital. Various
      denominators from hospital activity including beds, admissions and discharges
      have been used to obtain some standard ratios for comparing antibiotic
      consumption between hospitals and countries. Laboratory information systems in
      Clinical Microbiology Services are the primary resource for preparing cumulative
      reports on susceptibility testing results. This information is useful for
      planning empirical treatment and for adopting infection control measures. Among
      the supranational initiatives on resistance surveillance, the EARS-Net provides
      information about trends on antimicrobial resistance in Europe. Resistance is the
      consequence of the selective pressure of antibiotics, although in some cases
      these agents also promote resistance by favouring the emergence of mutations that
      are subsequently selected. Multiple studies have shown a relationship between
      antimicrobial use and emergence or resistance. While in some cases a decrease in
      antibiotic use was associated with a reduction in resistance rates, in many other
      situations this has not been the case, due to co-resistance and/or the low
      biological cost of the resistance mechanisms involved. New antimicrobial agents
      are urgently needed, which coupled with infection control measures will help to
      control the current problem of antimicrobial resistance. 

PMID- 24129286
TI  - Evaluating the quality of antimicrobial prescribing: is standardisation possible?
AB  - The quality of antimicrobial prescribing refers to the optimal way to use
      antibiotics in regard to their benefits, safety (e.g., resistance generation and
      toxicity) and cost. Evaluating the quality of antimicrobial prescribing in a way
      that focuses not only on reducing antimicrobial consumption but also on using
      them in a more optimal way allows us to understand patterns of use and to
      identify targets for intervention. The lack of standardisation is the primary
      problem to be addressed when planning an evaluation of antimicrobial prescribing.
      There is little information specifically describing an evaluation methodology.
      Information related to prescription evaluation can be obtained from the
      guidelines of Antimicrobial Stewardship Programs (ASPs) and from local and
      international experience. The criteria used to evaluate the quality of
      prescription should include the indication for antimicrobial therapy, the
      timeliness of initiation, the correct antibiotic choice (according to local
      guidelines), the dosing, the duration, the route of administration and the time
      at which to switch to oral administration. A locally developed guideline on
      antimicrobial therapy should preferably be the gold standard by which to evaluate
      the appropriatenes of prescriptions. Various approaches used to carry out the
      evaluations have been described in the literature. Repeated point-prevalence
      surveys (PPS) have been proven to be effective in identifying targets for quality
      improvement. Continuous prospective monitoring allows the identification of more
      precise intervention points at different times during prescription. The design of
      the study chosen to perform the evaluation should be adapted according to the
      resources available in each centre. Evaluating the quality of antimicrobial
      prescribing should be the first step to designing ASPs, as well as to evaluating
      their impact and the changes in prescribing trends over time. 

PMID- 24129287
TI  - Education on antibiotic use. Education systems and activities that work.
AB  - Education is a cornerstone of antimicrobial stewardships programs, because 50% of
      inappropriate antimicrobial prescriptions are a consequence of an imbalance
      between the high levels of knowledge required for the appropriate use of
      antibiotics and the scarce training offered to medical specialists. For this
      reason, programs optimizing antimicrobial (PROA) are essentially based on support
      and educational activities for prescribers. The educational activities are
      difficult to evaluate. In our country, the application of educational activities
      in antimicrobial training programs is very heterogeneous, although it has
      improved in recent years. We recommend the following educational measures, which
      are prioritized in order of effectiveness. Interactive educational interventions
      are the most effective. These are non-compulsory interventions based on real
      prescriptions in clinical practice and include educational outreach visits,
      audits and counseling interviews with feedback and multifaceted interventions.
      Passive educational strategies, with posters, newsletters, and dissemination of
      guidelines, are only marginally effective in changing antimicrobial prescribing
      practices and have not shown a sustained effect. These measures need extensive
      professional involvement and should be combined with more active approaches.
      Currently, interventions can be enhanced with some teaching tools in electronic
      format. Both interactive and passive educational measures should be integrated
      into the PROA and should have institutional support. Finally, we recommend
      including antimicrobials in the training plans of all clinical specialties. 

PMID- 24129288
TI  - How to assist clinicians in improving antimicrobial prescribing: tools and
      interventions provided by stewardship programs.
AB  - In the last decade, there has been an exponential increase in the microorganisms
      resistant to antimicrobials and a significant increase in the cost of these types
      of drugs. This phenomenon has increased interest in the development of
      interventions for counseling on and control of the use of antimicrobials,
      referred to as stewardship programs. In this article we review, from various
      points of view, the tools that have been developed with this purpose. First, we
      highlight the value of locally adapted guidelines and clinical pathways as an
      essential part of the operational process. Then we emphasize the importance of
      the relationship between microbiologists and clinicians for the accurate
      transmission of the information provided by blood cultures to make the most
      appropriate choice of antimicrobial for the patient's treatment. We also review
      the computerized tools that have facilitated the correct use of antimicrobials
      according to the controls established by the departments of pharmacy. Based on
      the previous tools, some programs based on "bedside recommendations" provided by
      multidisciplinary teams have been developed for optimizing the rational use of
      antimicrobials (PROA programs). Finally, we comment on the peculiarities of the
      programs targeting antifungals that have been developed in recent years. 

PMID- 24129289
TI  - Evaluation of new antimicrobials for the hospital formulary. Policies restricting
      antibiotic use in hospitals.
AB  - In Spain, the inclusion of new antibiotics in hospital formularies is performed
      by the Infection Policy Committee or the Pharmacy and Therapeutic Committee,
      although now the decision is moving to a regional level. Criteria for the
      evaluation of new drugs include efficacy, safety and cost. For antimicrobial
      drugs evaluation it is necessary to consider local sensibility and impact in
      bacterial resistance to determinate the therapeutic positioning. There is
      compelling evidence that the use of antibiotics is associated with increasing
      bacterial resistance, and a great number of antibiotics are used incorrectly. In
      order to decrease the inappropriate use of antibiotics, several approaches have
      been proposed. Limiting the use of antimicrobials through formulary restrictions,
      often aimed at drugs with a specific resistance profile, shows benefits in
      improving antimicrobial susceptibilities and decreasing colonization by drug
      resistant organisms. However, the restriction of one agent may result in the
      increased utilization of other agents. By using antibiotic cycling, the amount of
      antibiotics is maintained below the threshold where bacterial resistance
      develops, thus preserving highly efficient antibiotics. Unfortunately, cumulative
      evidence to date suggests that antibiotic cycling has limited efficacy in
      preventing antibiotic resistance. Finally, although there is still little
      clinical evidence available on antibiotic heterogeneity, the use of most of the
      existing antimicrobial classes could limit the emergence of resistance. This
      review summarizes information regarding antibiotic evaluation and available
      restrictive strategies to limit the use of antibiotics at hospitals with the aim
      of curtailing increasing antibiotic resistance. 

PMID- 24129290
TI  - Initiatives and resources to promote antimicrobial stewardship.
AB  - The development of an antimicrobial stewardship program (ASP) requires
      institutional support. However, obtaining sufficient institutional support is
      often a complex task that requires convincing the hospital's managers of the
      benefits of these programs. Additionally, in the design and implementation of an
      ASP, antimicrobial stewardship (AS) leaders need tools for diverse purposes, such
      as measuring antimicrobial consumption, education and training and designing
      protocols. In this review we provide useful information for AS promoters to
      facilitate the task of designing and implementing an ASP. First, we summarize
      information about various institutions that promote AS and include evidence that
      supports the need for and benefits of these programs. Then, several campaigns
      promoting AS are described. Finally, online resources for professionals dealing
      with AS are briefly summarized. 

PMID- 24129291
TI  - Scientific evidence and research in antimicrobial stewardship.
AB  - Evaluating the impact of antibiotic stewardship programs is challenging. There is
      evidence that they are effective in terms of reducing the consumption and cost of
      antibiotics, although establishing their impact on antimicrobial resistance
      (beyond restrictive policies in outbreaks caused by specific antimicrobial
      resistant organisms) and clinical outcomes is more difficult. Proper definitions
      of exposure and outcome variables, the use of advanced and appropriate
      statistical analyses and well-designed quasi-experimental studies would more
      accurately support the conclusions. Cluster randomized trials should be used
      whenever possible and appropriate, although the limitations of this approach
      should also be acknowledged. These issues are reviewed in this paper. We conclude
      that there are good research opportunities in the field of antibiotic
      stewardship. 

PMID- 24129292
TI  - Pulmonary cryptococcosis and cryptococcal osteomyelitis mimicking primary and
      metastatic lung cancer in (18)F-FDG PET/CT.

PMID- 24129293
TI  - Extracorporeal membrane oxygenation and lethal diseases: a new perspective.
AB  - Lethal cancer and chronic untreatable viral disease with life threatening
      consequences are among the major burden for morbidity and mortality in the
      western world. A large number of resources are employed every year in
      identification of new drugs to treat this condition. A remarkable percentage of
      resources are wasted for safety concerns about possible acute cardiac or
      pulmonary toxicity of the new identified compounds, that are rejected without
      further development even when promising. ExtraCorporeal Membrane Oxygenation
      (ECMO) is an established technique to support and replace cardio-pulmonary
      function that underwent rapid technologic improvement in the last years,
      resulting in reduced complication rate. ECMO has been used with success to treat
      acute life-threatening cardiac and pulmonary toxicity. Our hypothesis is that the
      new ECMO technological improvement could make this technique available to other
      setting, such as lethal cancer and infectious diseases, where it can provide a
      safe base to overwhelm acute cardiac and pulmonary toxicity of chemotoxic drugs
      and techniques. New drugs and old promising compounds rejected for toxicity could
      thus be re-introduced and employed, opening a new scenario in the treatment of
      life-threatening diseases. 

PMID- 24129294
TI  - [Extracranial stereotactic radiotherapy: a new arrow in the quiver].

PMID- 24129295
TI  - [Living donor liver donation - primum nihil nocere?].

PMID- 24129296
TI  - Acute cough illness in general practice - predictive value of clinical judgement
      and accuracy of requesting chest x-rays.
AB  - The aim of the study was to evaluate the accuracy of GPs' initial clinical
      judgement regarding presence or absence of pneumonia and to assess GPs' strategy
      for requesting chest X-rays in patients presenting with acute cough. GPs were
      asked to rate their suspicion of pneumonia based on clinical assessment alone and
      to protocol their decision to perform chest X-rays in 212 consecutive patients.
      These judgements were compared to the final diagnosis as determined by chest X
      ray or uneventful recovery (four weeks). After history taking and physical
      examination, GPs are highly accurate in judging which patients presenting with
      acute cough may have pneumonia (PPV 80% [95% CI 0,66-0,89]) or not (NPV 100% [95%
      CI 0,97-1,0]), and in which patients chest X-rays are required or not (spearman's
      rho 0,54, p<0,0001). 

PMID- 24129297
TI  - [How to deal with preoperative hypertension].
AB  - Although there only limited supportive evidence it is suggested that in the
      setting of elective surgery whenever possible one should aim for a normal
      preoperative blood pressure in hypertensive patients. If preoperative pressure is
      >180 mmHg (adequate and correct blood pressure measurement technique, whenever
      needed 24 h-ABPM) an elective surgical intervention should be postponed and blood
      pressure control should be optimized. Blood pressure of <180 mmHg is regarded as
      no contraindication for an elective surgical intervention. The perioperative risk
      in suboptimally treated hypertensive patients is not elevated as long as
      perioperative anesthesia handling is optimal and in the absence of relevant
      comorbidities. In summary present evidence suggests that the pre- and
      perioperative hypertension is a controllable risk factor of minor relevance.
      However this does not mean that one should ignore elevated preoperative blood
      pressure values. More than ten years ago an editorialist brought it to the point
      by saying: "Preoperative hypertension: remain wary? Yes - cancel surgery? No". 

PMID- 24129298
TI  - [Heart failure with preserved left ventricular ejection fraction].
AB  - Heart failure with preserved left ventricular ejection fraction (LVEF; HFpEF) is
      a common type of heart failure in the elderly, and it typically represents
      advanced hypertensive heart disease. The left ventricle in patients with HFpEF is
      characterized by concentric remodeling, normal LVEF, but reduced left
      longitudinal shortening, and importantly diastolic dysfunction. Dyspnoe and
      fatigue in patients with HFpEF are due to impaired left ventricular filling with
      a rapid increase in filling pressures and the lack of an increase in stroke
      volume during exercise. The diagnosis of HFpEF requires the careful exclusion of
      non-cardiac causes of dyspnoe as well as cardiac causes of dyspnoe associated
      with preserved LVEF other than HFpEF, primarily coronary artery disease and valve
      disease. Then, the following findings are required to make a diagnosis of HFpEF:
      a non-dilated left ventricle with an LVEF >50% and the presence of a significant
      diastolic impairment, which can be assessed using invasive haemodynamics,
      echocardiography, natriuretic peptides, or a combination of these tools. In
      contrast to patients with heart failure and reduced LVEF there is still no
      established treatment for patients with HFpEF, which prolongs survival or reduces
      the rate of hospitalizations for heart failure. There is currently however
      intense research going on in this field, and results from large trials evaluating
      the effects of various interventions on clinical endpoints are expected within
      the next years. 

PMID- 24129299
TI  - [Extracranial stereotactic radiotherapy for early-stage non-small cell lung
      cancer and oligometastases].
AB  - Stereotactic body radiotherapy (SBRT) is a new radiation technique that combines
      improvements in radiotherapy planning, intensity modulation and image guidance.
      The use of SBRT enables radiotherapy to be delivered instead of in six weeks in
      only a few days and with ablative total dose. Prospective phase II studies in
      patients with inoperable early stage non-small cell lung cancer demonstrate that
      the use of SBRT results in local control rates of 85-95% with acceptable
      toxicity. SBRT is also increasingly used for treatment of metastases in the lung,
      liver, retroperitoneum and in bones. Because SBRT enables a locally curative dose
      to be delivered in a time efficient manner this technique also opens up new
      perspectives for the treatment of patients with oligometastases. 

PMID- 24129300
TI  - [Examination of acute knee injuries].

PMID- 24129301
TI  - [Inhaled corticosteroids in subacute and chronic cough].

PMID- 24129302
TI  - [Thrombosis prophylaxis after hip surgery- aspirin is not inferior to heparin].

PMID- 24129303
TI  - [Acute congestive heart failure - salt and drinking quantity restriction without
      measureable benefit].

PMID- 24129305
TI  - [CME ultrasound diagnosis. 54. Incidental epigastric finding. GIST tumor of the
      gastric wall].

PMID- 24129308
TI  - Spin nutation effects in molecular nanomagnet-superconductor tunnel junctions.
AB  - We study the spin nutation effects of a molecular nanomagnet on the Josephson
      current through a superconductor|molecular nanomagnet|superconductor tunnel
      junction. We explicitly demonstrate that, due to the spin nutation of the
      molecular nanomagnet, two oscillatory terms emerge in the ac Josephson current in
      addition to the conventional ac Josephson current. Some resonances occur in the
      junction due to the interactions of the transported quasiparticles with the bias
      voltage and molecular nanomagnet spin dynamics. Their appearance indicates that
      the energy exchanged during these interactions is in the range of the
      superconducting energy gap. We also show that the spin nutation is able to
      convert the ac Josephson current to a dc current, which is interesting for
      applications. 

PMID- 24129310
TI  - A noticeable phenomenon: thiol terminal PEG enhances the immunogenicity of
      PEGylated emulsions injected intravenously or subcutaneously into rats.
AB  - Repeated intravenous injection of long-circulating methoxy-polyethylene glycol
      (PEG)-liposomes alters the pharmacokinetics and biodistribution of the second
      administration, regarded as the "accelerated blood clearance (ABC) phenomenon."
      Nevertheless, the effect of terminal groups of distearoylphosphatidylethanolamine
      polyethylene glycol (DSPE-PEG) on the induction of the ABC phenomenon had not
      been reported previously. In this study, rats were injected intravenously or
      subcutaneously with PEG coated emulsions (DE) which were prepared using PEG
      terminated with either the methoxyl (OCH3), hydroxyl (OH), amino (NH2), carboxyl
      (COOH), or thiol (SH) group. DE-OCH3 demonstrated the longest prolonged half-life
      in vivo after a single intravenous injection, followed by DE-SH and DE-COOH. In
      contrast, DE-OH was rapidly removed from the blood circulation, as was DE-NH2.
      Moreover, we observed a strong positive relationship between the circulation time
      of initially injected PEGylated emulsions and the extent to which the ABC
      phenomenon was induced, but a exception of DE-SH increasing the ABC effect.
      Furthermore, the present study suggested that thiols might stimulate the
      proliferation and differentiation of B cells to induce the fastest clearance of
      the second intravenous administration by inducing the synthesis of the cell
      membrane and cytosolic proteins or reacting with follicular dendritic cells. The
      results strongly suggested that thiol groups played a stimulatory role in the
      immune response and provided a considerable implication for multiple drug therapy
      of thiol groups. 

PMID- 24129311
TI  - Cysteine modified rare-earth up-converting nanoparticles for in vitro and in vivo
      bioimaging.
AB  - Cysteine, as a small organic molecule and amino acid, is a basic building block
      for proteins and has special physiological functions in vivo. Cysteine has strong
      affinity for cells, which can be taken advantage for various applications. A new
      and facile surface modification method has been developed for rare-earth doped
      upconversion nanoparticles (UCNs) using cysteine. Compared with unmodified
      samples, the water-solubility and biocompatibility of the cysteine modified
      NaYF4:Yb,Er and NaYF4:Yb,Tm UCNs (termed as UCN-Er-Cys and UCN-Tm-Cys,
      respectively) have been significantly improved, while their particle size and
      emission properties did not change substantially. Due to the low cytotoxicity as
      revealed by methyl thiazolyl tetrazolium assay, the cysteine modified UCNs were
      successfully applied to imaging of Hela cells in vitro and nude mouse in vivo.
      Most significant is that the method offers the advantages of ease of synthesis
      and handling as well as potentially low cost for biomedical emerging
      applications.

PMID- 24129312
TI  - Inhibition of human neutrophil activity by an RNA aptamer bound to interleukin-8.
AB  - Interleukin-8 (IL-8) is a proinflammatory CXC chemokine that has been associated
      with the promotion of neutrophil chemotaxis, degranulation, and the pathogenesis
      of several neutrophil-infiltrating chronic inflammatory diseases. In the current
      study, we generated and characterized a 2'-fluoro-pyrimidine modified RNA aptamer
      (8A-35) against human IL-8. The 8A-35 aptamer binds to IL-8 with high specificity
      and affinity, yielding an estimated K(D) of 1.72 pM. NMR data revealed that the
      residues of Lys8, Leu10, Val63, Val66, Lys69 and Ala74 of IL-8 interact with
      aptamer. Moreover, the 8A-35 aptamer has a potent IL-8-neutralizing activity that
      can modulate multiple biological activities of IL-8 in human neutrophils,
      including migration, intracellular signaling, and intracellular Ca(2+)
      mobilization. Our results suggest that the 8A-35 aptamer has great potential to
      be a lead structure in the development of effective therapeutic agents against
      inflammatory diseases.

PMID- 24129314
TI  - Effect of pH on cellulase production and morphology of Trichoderma reesei and the
      application in cellulosic material hydrolysis.
AB  - A low-cost of cellulase achieved through improving fermentation technology
      remains a key requirement for commercialization of cellulosic biofuels and
      biochemicals. pH plays a very important role in the process of cellulase
      synthesis by Trichoderma reesei. In this work, effects of pH on the production
      and production rates of three cellulase components (endoglucanase, exoglucanase,
      beta-glucosidase) and mycelial morphology were studied. Production rates of the
      cellulase components were kept highest and the mycelial morphology was maintained
      at the optimal status by developing a phased pH control strategy in order to
      improve cellulase production. Cellulase production in terms of filter paper
      activity and beta-glucosidase production in batch fermentation increased 17.6%
      and 22%. Saccharification efficiency of the enzyme obtained by pH control was
      evaluated by hydrolyzing pretreated corn cob. Saccharification yield increased
      significantly (up to 26.2%) compared with that without pH control. These results
      add new knowledge on approach for improving cellulase production. 

PMID- 24129315
TI  - Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.
AB  - Protein methylation is a common posttranslational modification that mostly occurs
      on arginine and lysine residues. Arginine methylation has been reported to
      regulate RNA processing, gene transcription, DNA damage repair, protein
      translocation, and signal transduction. Lysine methylation is best known to
      regulate histone function and is involved in epigenetic regulation of gene
      transcription. To better study protein methylation, we have developed highly
      specific antibodies against monomethyl arginine; asymmetric dimethyl arginine;
      and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used
      to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS
      analysis to identify and quantify arginine and lysine methylation sites in
      several model studies. Overall, we identified over 1000 arginine methylation
      sites in human cell line and mouse tissues, and ~160 lysine methylation sites in
      human cell line HCT116. The number of methylation sites identified in this study
      exceeds those found in the literature to date. Detailed analysis of arginine
      methylated proteins observed in mouse brain compared with those found in mouse
      embryo shows a tissue-specific distribution of arginine methylation, and extends
      the types of proteins that are known to be arginine methylated to include many
      new protein types. Many arginine-methylated proteins that we identified from the
      brain, including receptors, ion channels, transporters, and vesicle proteins, are
      involved in synaptic transmission, whereas the most abundant methylated proteins
      identified from mouse embryo are transcriptional regulators and RNA processing
      proteins. 

PMID- 24129316
TI  - Costs of adalimumab versus infliximab as first-line biological therapy for
      luminal Crohn's disease.
AB  - BACKGROUND AND AIMS: Randomised controlled trials demonstrate that the anti
      tumour necrosis factor-alpha (anti-TNFalpha) therapies infliximab and adalimumab
      are effective in inducing remission and preventing relapse of Crohn's disease
      (CD). As few studies have compared costs and efficacy of these two drugs
      directly, we examined this issue. METHODS: Data were collected for patients
      receiving either drug as first-line anti-TNFalpha for CD. Patients were matched
      as closely as possible on age, gender, weight, height, and date of commencement
      of therapy. Response to induction therapy was assessed at 12weeks, and sustained
      clinical benefit at last point of follow-up. Resource data were collected for all
      patients until study end, with National Health Services reference costs applied
      to calculate the total cost per patient with adalimumab compared with infliximab.
      RESULTS: Thirty-six patients had been treated with adalimumab as first-line anti
      TNFalpha since 2010. We matched an identical number of infliximab patients.
      Demographic data were similar between the two groups. Costs were significantly
      lower with adalimumab (L6692.95 less per patient (95% confidence interval
      L1816.61-L11569.29)), which was largely driven by the drug costs and drug
      administration costs associated with infliximab. Twenty-nine (80.6%) patients
      responded to induction therapy with both drugs, and 22 (61.1%) achieved
      glucocorticosteroid-free sustained clinical benefit with either drug at last
      point of follow-up. CONCLUSIONS: Costs of infliximab used as first-line anti
      TNFalpha therapy are greater, which may have implications for selection. Clinical
      outcomes appeared comparable, although power to detect a statistically
      significant difference would be limited.

PMID- 24129317
TI  - A mediation model linking dispatcher leadership and work ownership with safety
      climate as predictors of truck driver safety performance.
AB  - The study was designed to test the effect of safety climate on safety behavior
      among lone employees whose work environment promotes individual rather than
      consensual or shared climate perceptions. The paper presents a mediation path
      model linking psychological (individual-level) safety climate antecedents and
      consequences as predictors of driving safety of long-haul truck drivers. Climate
      antecedents included dispatcher (distant) leadership and driver work ownership,
      two contextual attributes of lone work, whereas its proximal consequence included
      driving safety. Using a prospective design, safety outcomes, consisting of hard
      braking frequency (i.e. traffic near-miss events) were collected six months after
      survey completion, using GPS-based truck deceleration data. Results supported the
      hypothesized model, indicating that distant leadership style and work ownership
      promote psychological safety climate perceptions, with subsequent prediction of
      hard-braking events mediated by driving safety. Theoretical and practical
      implications for studying safety climate among lone workers in general and
      professional drivers in particular are discussed. 

PMID- 24129318
TI  - Prevalence of synthetic cannabinoids in blood samples from Norwegian drivers
      suspected of impaired driving during a seven weeks period.
AB  - From early year 2000 different herbal products containing synthetic cannabinoids
      (SC) have appeared on the drug market all over the world, and new substances are
      frequently introduced. The prevalence of SC use in different populations is
      however still mainly unknown, also in Norway. This information is difficult to
      obtain, but studies of drivers suspected of driving under the influence of drugs
      (DUID), might provide important information. The aim of this study was to assess
      the prevalence of SC in drivers suspected of being under the influence of drugs
      in Norway, and investigate if SCs impair driving performance. For two periods of
      three and four weeks all blood samples from drivers suspected of DUID in Norway
      were analyzed for the presence of 12 and 18 different SCs, respectively. A new
      ultra performance liquid chromatography tandem mass spectrometry method was
      developed. A total of 726 cases were analyzed during our study period, and SCs
      were detected in 16 cases (2.2%) in total. The mean age of these drivers was 29.6
      years. High concentrations of other psychoactive drugs were detected in all the
      blood samples where a SC was found. AM-2201 and JWH-018 were the most frequently
      detected SCs, each found in five cases. In addition RSC-4, JWH-122, JWH-081 and
      JWH-250 were detected. None of the drivers had reported using SCs prior to
      driving. Despite the limited number of SCs investigated in this 7 week study
      period, a considerable percent of the cases were positive. Other psychoactive
      drugs of abuse were always found concomitant with the SCs, and the age of these
      drivers indicates that experienced drug users also ingest SCs. Since other drugs
      were found in all the samples, the psychomotor impairment caused by the SCs is
      difficult to estimate. Our study shows the importance of screening analyses of
      biological samples from different populations to assess the prevalence of drug
      use, since self-reporting might be encumbered with significant under-reporting. 

PMID- 24129319
TI  - Freeway safety estimation using extreme value theory approaches: a comparative
      study.
AB  - The validity of traffic conflicts and other surrogate events has been a great
      concern in the development and application of surrogate safety measures. Extreme
      value theory (EVT) offers a strong modeling framework for linking surrogate
      measures of safety to crash frequency. This study aims at developing, validating,
      and comparing two EVT modeling approaches for characterizing extreme events. The
      two alternative EVT approaches, block maxima (BM) and peak over threshold (POT),
      are used to relate surrogates and lane change maneuver-related crashes on
      freeways. The surrogate measure is post encroachment times measured from 4189
      lane change maneuvers recorded at 29 directional freeway segments with
      approximately 3-h observation for each segment. The sample size, serial
      dependency, and non-stationarity issues for both approaches are examined. The
      comparison of results from the two modeling approaches indicates that the POT
      approach performs better than BM approach from the aspects of data utilization,
      estimate accuracy and estimate reliability. This conclusion is drawn on condition
      of relatively short time observations. An additional comparison is conducted
      between the estimated crashes and estimated return levels from two approaches.
      Due to large variances in the estimated crashes, much more robust estimated
      return levels are recommended for freeway safety evaluation. 

PMID- 24129320
TI  - A parametric duration model of the reaction times of drivers distracted by mobile
      phone conversations.
AB  - The use of mobile phones while driving is more prevalent among young drivers-a
      less experienced cohort with elevated crash risk. The objective of this study was
      to examine and better understand the reaction times of young drivers to a traffic
      event originating in their peripheral vision whilst engaged in a mobile phone
      conversation. The CARRS-Q advanced driving simulator was used to test a sample of
      young drivers on various simulated driving tasks, including an event that
      originated within the driver's peripheral vision, whereby a pedestrian enters a
      zebra crossing from a sidewalk. Thirty-two licensed drivers drove the simulator
      in three phone conditions: baseline (no phone conversation), hands-free and
      handheld. In addition to driving the simulator each participant completed
      questionnaires related to driver demographics, driving history, usage of mobile
      phones while driving, and general mobile phone usage history. The participants
      were 21-26 years old and split evenly by gender. Drivers' reaction times to a
      pedestrian in the zebra crossing were modelled using a parametric accelerated
      failure time (AFT) duration model with a Weibull distribution. Also tested where
      two different model specifications to account for the structured heterogeneity
      arising from the repeated measures experimental design. The Weibull AFT model
      with gamma heterogeneity was found to be the best fitting model and identified
      four significant variables influencing the reaction times, including phone
      condition, driver's age, license type (provisional license holder or not), and
      self-reported frequency of usage of handheld phones while driving. The reaction
      times of drivers were more than 40% longer in the distracted condition compared
      to baseline (not distracted). Moreover, the impairment of reaction times due to
      mobile phone conversations was almost double for provisional compared to open
      license holders. A reduction in the ability to detect traffic events in the
      periphery whilst distracted presents a significant and measurable safety concern
      that will undoubtedly persist unless mitigated. 

PMID- 24129321
TI  - The effects of situational factors and impulsiveness on drivers' intentions to
      violate traffic rules: Difference of driving experience.
AB  - This study aimed to explore the effects of situational variables and
      impulsiveness on drivers' intentions to violate traffic rules among novice, less
      experienced and experienced drivers in China. Specifically, eight scenarios with
      manipulated variables, including time pressures (high and low), descriptive norms
      (positive and negative) and accident base rates (high and low), were randomly
      presented to 232 drivers. All independent variables, except the descriptive norm,
      were between-subjects designs. The results showed that hypothetical high time
      pressure and unsafe descriptive norm increased drivers' intentions to commit
      violations, respectively. Moreover, the effects of situational factors and
      impulsiveness on their intentions to violate traffic rules depended on driving
      experience. Cognitive impulsiveness predicted the violation intention only of
      novice drivers, whereas the descriptive norm affected the intention of the
      remaining two groups. The stated accident base rate moderated the relationship
      between the descriptive norm and violation intention of experienced drivers,
      specifically, when the accident base rate was hypothetical high their violation
      intention relied more on descriptive norms. The results indicated that with
      increased driving experience, drivers became more sensitive to situational cues,
      less influenced by individual factors and, correspondingly, more likely to behave
      in a manner that was congruent with the surrounding situation and individuals.
      The potential applications for this research are the development of intervention
      and training programs specifically for drivers with varying levels of driving
      experience. 

PMID- 24129322
TI  - Estimating the subjective risks of driving simulator accidents.
AB  - We examine the subjective risks of driving behavior using a controlled virtual
      reality experiment. Use of a driving simulator allows us to observe choices over
      risky alternatives that are presented to the individual in a naturalistic manner,
      with many of the cues one would find in the field. However, the use of a
      simulator allows us the type of controls one expects from a laboratory
      environment. The subject was tasked with making a left-hand turn into incoming
      traffic, and the experimenter controlled the headways of oncoming traffic.
      Subjects were rewarded for making a successful turn, and lost income if they
      crashed. The experimental design provided opportunities for subjects to develop
      subjective beliefs about when it would be safe to turn, and it also elicited
      their attitudes towards risk. A simple structural model explains behavior, and
      showed evidence of heterogeneity in both the subjective beliefs that subjects
      formed and their risk attitudes. We find that subjective beliefs change with
      experience in the task and the driver's skill. A significant difference was
      observed in the perceived probability to successfully turn among the
      inexperienced drivers who did and did not crash even though there was no
      significant difference in drivers' risk attitudes among the two groups. We use
      experimental economics to design controlled, incentive compatible tasks that
      provide an opportunity to evaluate the impact on driver safety of subject's
      subjective beliefs about when it would be safe to turn as well as their attitudes
      towards risk. This method could be used to help insurance companies determine
      risk premia associated with risk attitudes or beliefs of crashing, to better
      incentivize safe driving. 

PMID- 24129323
TI  - Forearm post-traumatic deformities: classification and treatment.
AB  - INTRODUCTION: There is no classification for acquired forearm deformities. A
      clinical-radiographic study was conducted to classify these deformities and
      evaluate the results. MATERIALS AND METHODS: Thirteen patients with forearm
      deformities following traumas or their treatment were included (11 men and two
      women, from 2000 to 2010). Mean age was 31 years (range 10-75 years). Initial
      treatment was conservative in five patients and surgical in eight patients. One
      segment was affected in seven patients (the radius in four patients, the ulna in
      three), and both segments were affected in six patients. Location assessment: 2
      projections X-rays, including wrist and elbow. Deformity location: proximal,
      diaphisary, distal, defined with the abbreviation, in distal sense, R1, R2, R3
      for the radius, and U1, U2, U3 for the ulna. Primary and secondary deformities
      were distinguished: secondary deformities occurred later in a different location
      than the primary one. Six patients were treated with plate and screws. An
      external fixator was used in six patients. One patient was treated with bone
      resection. Iliac crest bone graft was used in 10 patients, and vascularised
      fibula graft in one patient. RESULTS: The primary deformity affecting the radial
      diaphysis (R2) determined a secondary deformity in four patients: in the distal
      ulna (U3) with ulnocarpal dislocation in three patients and in the distal radius
      (R3) in one patient. Results of osteosynthesis treatment were excellent in one
      patient, satisfactory in four and unsatisfactory in one. External fixation was
      excellent in one patient and satisfactory in five. Bone resection was
      satisfactory in one patient. DISCUSSION: Surgical treatments with osteosynthesis
      are the major cause of acquired forearm deformities in adults. Location and
      aetiology of the deformities are essential for the surgical indication and the
      result. It is important to restore the length of the deformed segment, realigning
      the anatomical axis. X-rays enable clinicians to distinguish between primary and
      secondary forearm deformities. CONCLUSION: Characteristics and locations of post
      traumatic deformities were identified. The major location is diaphisary and
      distal, the elbow is rarely affected. The functional consequence is a limitation
      in the range of motion of the hand. The best results are achieved with short-term
      treatment.

PMID- 24129324
TI  - Re: Is there a need for a clinical decision rule in blunt wrist trauma?

PMID- 24129325
TI  - The relationship between patient volume and mortality in American trauma centres:
      a systematic review of the evidence.
AB  - OBJECTIVE: To synthesise published and unpublished findings examining the
      relationship between institutional trauma centre volume or trauma patient volume
      per surgeon and mortality. BACKGROUND: Evidence on the relationship between
      patient volume and survival in trauma patients is inconclusive in the literature
      and remains controversial. METHODS: A literature search was performed to identify
      studies published between 1976 and 2013 via MEDLINE (Pubmed) and the Cumulative
      Index to Nursing and Allied Health Literature (EbscoHost) as well as footnote
      chasing. Abstracts from appropriate conferences and ProQuest Dissertations and
      Theses were also searched. Inclusion criteria required studies to be original
      research published in English that examined the relationship between mortality
      and either institutional or per surgeon volume in American trauma centres. We
      employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) Statement checklist and flowchart. The Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) approach was employed to rate the
      quality of the evidence. RESULTS: Of 1392 studies reviewed, 19 studies met
      defined inclusion criteria; all studies were retrospective. The definition of
      volume was heterogeneous across the studies. Patient population and analysis
      methods also varied across the studies. Sixteen studies (84%) examined the
      relationship between institutional trauma centre volume and mortality. Of the 16
      studies, 12 examined the volume of severely injured patients and eight examined
      overall trauma patient volume. High institutional volume was associated with at
      least somewhat improved mortality in ten of 16 studies (63%); however, nearly
      half of these studies found only some subpopulations experienced benefits. In the
      remaining six studies, volume was not associated with any benefits. Four studies
      (25%) analysed the impact of surgeon volume on mortality. High volume per surgeon
      was associated with improved mortality in only one of four studies (25%).
      CONCLUSIONS: The studies were extremely heterogeneous, thus definitive
      conclusions cannot be drawn regarding optimal volume before a clear advantage in
      survival is observed. A prospective study defining volume as a continuous
      variable is warranted to support current admission criteria for American trauma
      patients.

PMID- 24129326
TI  - Reconstruction of traumatic losses of substance at the elbow.
AB  - Traumatic lesions at the elbow involving great loss of substance are uncommon,
      but represent a significant problem when such cases are referred to a trauma
      department. Most of these injuries may cause severe final functional impairment,
      thereby jeopardising future activities, particularly in cases where treatment was
      delayed or inappropriate. The timing and method of treatment are critical. The
      trauma may involve soft tissues only, or bone and joint, or several structures at
      the same time, which results in combined complex tissue defects. Each type of
      tissue loss should be managed by choosing the most suitable technique from the
      armamentarium of reconstructive surgery, taking into account different priorities
      and the optimum timing (immediate or delayed, one- or two-stages). The authors
      describe a spectrum of indications and techniques that can be useful tools in
      managing these injuries. 

PMID- 24129327
TI  - To fix or not to fix? The role of fibular fixation in distal shaft fractures of
      the leg.
AB  - BACKGROUND: The role of stabilisation of the fibula in distal two-bone fractures
      of the leg is controversial. Some studies indicate the need for fibular
      stabilisation in 43 AO fractures, but few studies consider the role of the fibula
      in 42 AO fractures. The aim of the current paper is to explain the role of
      stabilisation of the fibula in 42 AO fractures, correlating the rates of healing
      and non-union between patients with and without fibula fixation. MATERIALS AND
      METHODS: A total of 60 patients with 42 AO (distal) shaft fracture of the tibia
      with associated fracture of the fibula were selected. Patients were divided into
      two groups according to whether or not the fibula was fixed: Group I (n=26)
      comprised patients who had their fibula fixed while Group II (n=34) comprised
      patients who did not. The fibular fracture was classified according to the AO and
      related to the level of the tibial fracture. Other parameters examined were the
      union rate of the two groups correlated to the fracture pattern and position of
      the fibular fracture; the demographic data, such as age and gender; the presence
      of an open fracture, and the type of tibial fixation device used (nail or plate).
      RESULTS: None of the parameters considered (open injury, AO classification,
      device used and level of the fibular fracture relative to the tibial) were shown
      to have an influence on the development of a non-union. CONCLUSION: This study
      showed a higher non-union rate when the fracture of the tibia and fibula were at
      the same level, the tibia was fixed with a bridging plate and the fibula left
      untouched. For this reason, we recommend fibular fixation in all 42 distal
      fractures when both fractures lie on the same plane and the tibial fracture is
      relatively stabilised.

PMID- 24129328
TI  - Universal phonon mean free path spectra in crystalline semiconductors at high
      temperature.
AB  - Thermal conductivity in non-metallic crystalline materials results from
      cumulative contributions of phonons that have a broad range of mean free paths.
      Here we use high frequency surface temperature modulation that generates non
      diffusive phonon transport to probe the phonon mean free path spectra of GaAs,
      GaN, AlN, and 4H-SiC at temperatures near 80 K, 150 K, 300 K, and 400 K. We find
      that phonons with MFPs greater than 230 +/- 120 nm, 1000 +/- 200 nm, 2500 +/- 800
      nm, and 4200 +/- 850 nm contribute 50% of the bulk thermal conductivity of GaAs,
      GaN, AlN, and 4H-SiC near room temperature. By non-dimensionalizing the data
      based on Umklapp scattering rates of phonons, we identified a universal phonon
      mean free path spectrum in small unit cell crystalline semiconductors at high
      temperature. 

PMID- 24129329
TI  - Chiral suprastructures of asymmetric oligothiophene-hybrids induced by a single
      proline.
AB  - Oligothiophene-proline hybrids were synthesized via click-reaction showing
      intriguing self-assembly behavior in an aqueous environment by forming chiral
      superstructures, whose helicity is controlled by the configuration of the amino
      acid moiety. 

PMID- 24129330
TI  - Synthesis and characterization of micelles as carriers of non-steroidal anti
      inflammatory drugs (NSAID) for application in breast cancer therapy.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDS) are emerging as a particularly
      valuable class of drugs due to their recently reported anti-tumoral activity in
      colorectal cancer. However, despite this tremendous potential, their
      bioavailability at the tumor microenvironment remains rather limited. To overcome
      this issue, in this work we synthesized biocompatible micellar nanocarriers
      composed of amphiphilic chitosan to deliver ibuprofen into breast cancer cells
      and evaluate its anti-tumor activity, while avoiding side-effects. Our results
      reveal that the formulations produced herein self-assembly into spherical
      micelles with suitable sizes for tumor accumulation (108-252 nm). Furthermore, by
      using a vortex-sonication method, ibuprofen was successfully encapsulated with
      high efficiency. Cell uptake studies show that ibuprofen-loaded micelles are
      readily internalized by tumor cells and deliver their cargo in the intracellular
      compartment as demonstrated by confocal microscopy images. This fact led to a
      remarkable reduction in cancer cell viability (<13%), at a relatively low drug
      dosage, illustrating the anti-tumoral activity of ibuprofen when delivered to
      breast cancer cells. These findings demonstrate the promising potential of
      chitosan micelles as carriers of cost-effective NSAIDS for application in breast
      cancer therapy.

PMID- 24129331
TI  - Bio-responsive chitin-poly(L-lactic acid) composite nanogels for liver cancer.
AB  - Hepatic carcinoma (HCC) is one of the most common cancer and its treatment has
      been considered a therapeutic challenge. Doxorubicin (Dox) is one of the most
      important chemotherapeutic agents used in the treatment for liver cancer.
      However, the efficacy of Dox therapy is restricted by the dose-dependent toxic
      side effects. To overcome the cardiotoxicity of Dox as well as the current
      problems of conventional modality treatment of HCC, we developed a locally
      injectable, biodegradable, and pH sensitive composite nanogels for site specific
      delivery. Both control and Dox loaded composite nanogel systems were analyzed by
      DLS, SEM, FTIR and TG/DTA. The size ranges of the control composite nanogels and
      their drug loaded counterparts were found to be 90+/-20 and 270+/-20 nm,
      respectively. The control chitin-PLA CNGs and Dox-chitin-PLA CNGs showed higher
      swelling and degradation in acidic pH. Drug entrapment efficiency and in vitro
      drug release studies were carried out and showed a higher drug release at acidic
      pH compared to neutral pH. Cellular internalization of the nanogel systems was
      confirmed by fluorescent microscopy. The cytotoxicity of the composite nanogels
      was analyzed toward HepG2 (human liver cancer) cell lines. Furthermore, the
      results of in vitro hemolytic assay and coagulation assay substantiate the blood
      compatibility of the system. Overall Dox-chitin-PLA CNGs system could be a
      promising anticancer drug delivery system for liver cancer therapy.

PMID- 24129332
TI  - Fronto-parietal network: flexible hub of cognitive control.
AB  - A recent study shows that the fronto-parietal network (FPN), and subregions
      therein, alters its functional connectivity with nodes of other networks based on
      task goals. Moreover, FPN patterns of connectivity not only reflect engagement of
      specific tasks, but also serve as a code that can be transferred to facilitate
      learning novel tasks. 

PMID- 24129333
TI  - Topographic representation of high-level cognition: numerosity or sensory
      processing?
AB  - A recent study showed that topographic field maps of complex cognitive functions,
      such as numerosity, exist in the human brain. This is an exciting, novel approach
      for studying the neural representation of high-level cognition. However, the
      results can also be explained on the basis of the confounding non-numerical
      sensory cues of numerosity. 

PMID- 24129334
TI  - Bronchoscopic and nonbronchoscopic methods of airway culturing in tracheostomized
      children.
AB  - INTRODUCTION: Distal airway secretions can be sampled by bronchoscopic
      bronchoalveolar lavage (B-BAL), blind protected BAL (BP-BAL), and tracheal
      aspiration (TA). We quantitatively compared the cultures of distal airway
      secretions from BP-BAL, B-BAL, and TA specimens, and assessed the efficacy of the
      three above methods in diagnosing bronchitis in tracheostomized children.
      METHODS: Twenty children with tracheostomies underwent BP-BAL, B-BAL, and TA.
      Samples were sent for quantitative bacterial cultures. The diagnosis of
      bronchitis was made based on a validated visual grading system as well as on
      positive quantitative cultures from the BAL fluid. Diagnostic agreement between
      cultures obtained by the three methods and the visual grading scores was
      determined by kappa statistics. RESULTS: The diagnosis of bronchitis by visual
      grading score had substantial agreement with BP-BAL, moderate agreement with B
      BAL, and fair agreement with TA results. BP-BAL specimens had significantly lower
      pathogenic colonies (P < .05) than either B-BAL or TA specimens. CONCLUSIONS: BP
      BAL allows for more accurate sampling of lower airway secretions in
      tracheostomized children and is more accurate in the diagnosis of bronchitis in
      this group.

PMID- 24129335
TI  - Examination of patterns in intubation by an emergency airway team at a large
      academic center: higher frequency during daytime hours.
AB  - BACKGROUND: Emergency airway management represents an event with high acuity but
      unpredictable frequency and therefore presents a challenge for adequate staffing.
      Given circadian and seasonal variations, we hypothesized that the majority of
      emergency airway events happen after normal working hours and during the winter
      months. METHODS: A retrospective analysis of 1,482 intubations by an emergency
      airway team over a 3-y period was performed. The data were obtained from
      hospitalized patients who required emergency airway management in a large
      academic medical center. A database of emergency airway consultations was
      analyzed for intubation time and date information, as well as geographic location
      within the hospital. RESULTS: A greater percentage of emergency intubations
      occurred during day shift hours (7 am to 7 pm) compared with night shift hours,
      57% and 43%, respectively (P < .01). The monthly frequency of intubations was not
      uniformly distributed across the year (P < .01). The greatest percentage of
      intubations was performed in February (10.9%), with the lowest being recorded in
      August (4.7%). CONCLUSIONS: Emergency airway service utilization is highest
      during daytime hours, with seasonal variations composed of higher consults in the
      winter and lower consults in the summer.

PMID- 24129336
TI  - Vibration response imaging in idiopathic pulmonary fibrosis: a pilot study.
AB  - BACKGROUND: Vibration response imaging (VRI) is a novel imaging technique and
      little is known about its characteristics and diagnostic value in idiopathic
      pulmonary fibrosis (IPF). The aim of this study was to investigate the features
      of VRI in subjects with IPF. METHODS: We enrolled 23 subjects with IPF (42-74 y
      old) and 28 healthy subjects (42-72 y old). Subjects with IPF were diagnosed by
      lung biopsy and underwent VRI, spirometry, lung diffusion testing, and chest x
      ray or computed tomography, which entailed assessment of the value of VRI
      indices. RESULTS: The total VRI score correlated statistically with single-breath
      carbon monoxide diffusing capacity percent predicted (r = -0.30, P = .04), but
      not with FVC percent predicted, FEV1 percent predicted, and FEV1/FVC (r = -0.27, 
      0.22, and 0.19; all P > .05). Compared with healthy subjects (17.9%), 20 subjects
      with IPF (86.96%, P < .01) presented with significantly increased crackles. The
      difference in quality lung data in all lung regions was unremarkable (all P >
      .05), except for the upper right and lower left lobes (P < .05). Overall, VRI
      parameters yielded acceptable assay sensitivity and specificity. Maximum energy
      frame was characterized by the highest diagnostic value (sensitivity, 1.00;
      specificity, 0.82), followed by presence of abundant crackles (sensitivity, 0.70;
      specificity, 0.96). Total VRI score was not a sensitive indicator of IPF, owing
      to low assay sensitivity (0.70) and specificity (0.64). CONCLUSIONS: VRI may be
      helpful to discriminate between IPF subjects and healthy individuals. Maximum
      energy frame and abundant crackles might serve as a diagnostic tool for IPF.

PMID- 24129337
TI  - Twitch mouth pressure and disease severity in subjects with COPD.
AB  - INTRODUCTION: Patients with COPD have impaired respiratory muscle strength.
      Twitch mouth pressure (Ptw,m) in response to magnetic stimulation of the cervical
      nerve has been suggested to clinically reflect inspiratory muscle strength.
      However, studies on Ptw,m values and their relationship with disease severity are
      limited. Thus, we tested the Ptw,m values of subjects with COPD and investigated
      the relationship of these values with disease severity. METHODS: We recruited 75
      COPD patients and 63 age-matched controls. All participants were tested for
      Ptw,m, sniff nasal pressure (SNIP), and maximum static inspiratory mouth pressure
      (PImax ); the BODE (body mass index, air flow obstruction, dyspnea, exercise
      capacity) index was evaluated for overall severity assessment and the 6-min walk
      distance (6MWD) was used to determine the exercise capacity of subjects with
      COPD. RESULTS: Subjects with COPD had markedly lower Ptw,m values compared with
      the controls (10.00 +/- 2.17 vs 13.66 +/- 2.20 cm H2O for males, 8.83 +/- 0.89 vs
      11.81 +/- 1.98 cm H2O for female; each with P < .001). The Ptw,m values decreased
      with increasing COPD severity, and similar trends were observed in the SNIP and
      PImax values. Regression correlation analysis showed that Ptw,m values were
      significantly correlated inversely with the BODE index (R = 0.65, P < .001) but
      positively correlated with 6MWD (R = 0.59, P < .001) in the COPD group; the SNIP
      values of subjects with COPD were also correlated inversely with their BODE index
      (R = 0.49, P < .001) but positively correlated with their 6MWD (R = 0.33, P <
      .005). CONCLUSIONS: Ptw,m values are 26.8% lower in male subjects with COPD and
      25.3% lower in female subjects with COPD compared with the controls. The Ptw,m
      values of subjects with COPD decrease with increasing disease severity. Ptw,m was
      better correlated with the BODE index and exercise capacity than SNIP and PImax ,
      which suggests that Ptw,m more accurately reflects the overall severity and
      burden of COPD.

PMID- 24129338
TI  - Checklists for powder inhaler technique: a review and recommendations.
AB  - Turbuhaler and Diskus are commonly used powder inhaler devices for patients with
      respiratory disease. Their effectiveness is limited in part by a patient's
      ability to use them correctly. This has led to numerous studies being conducted
      over the last decade to assess the correct use of these devices by patients and
      health care professionals. These studies have generally used device-specific
      checklists to assess technique, this being the most feasible and accessible
      method for assessment. However, divergence between the checklists and scoring
      systems for the same device in different studies makes direct comparison of
      results difficult and at times inappropriate. Little evidence is available to
      assess the relative importance of different criteria; however, brief patient
      training based on specific inhaler technique checklists leads to significant
      improvement in asthma outcomes. This paper reviews common checklists and scoring
      systems used for Turbuhaler and Diskus, discusses the problem of heterogeneity
      between different checklists, and finally recommends suitable checklists and
      scoring systems for these devices based on the literature and previous findings.
      Only when similar checklists are used across different research studies will
      accurate comparisons and meta-analysis be possible.

PMID- 24129339
TI  - Structural diversity in hybrid vanadium(IV) oxyfluorides based on a common
      building block.
AB  - There are only limited reports on vanadium(iv) oxyfluorides (VOFs) with extended
      crystal structures. Here we expand and enrich the list of existing VOFs with a
      series of 14 new materials "VOF-n (n = 1-14)" prepared using ionothermal and
      solvothermal synthesis methods. All of these materials arise from the
      condensation of a dimeric structural motif. These VOFs can be classified into
      three groups depending on their key structural features; layer structures: VOF
      1"[HN2C7H6][V2O2F5]", VOF-2"[HN2C4H4][V2O2F5]", VOF-3"[HN2C3H4][V2O2F5]" and VOF
      4"V2(N2C4H4)O2F4", ladder like structures: VOF-5"[NH4(HN2C3H4)][V2O2F6]", VOF
      6"[K(HN2C3H4)][V2O2F6]", VOF-7"[HNH2CH2CH3][VOF3]", VOF-8"[HN2C7H6][VOF3]", VOF
      9"[H2N2C4H6][V2O2F6]", VOF-10"beta-RbVOF3", VOF-11"alpha-KVOF3", VOF-12"beta
      KVOF3", VOF-13"[H2(NH2)2(CH2)2][V2O2F6]", and a chain structure: VOF
      14"[H2N2C6H12][V2O2F7]". The crystal structures of VOF-n are presented, and their
      synthetic and structural relationships are discussed. 

PMID- 24129340
TI  - Metal/nanowire contacts, quantum confinement, and their roles in the generation
      of new, gigantic actions in nanowire transistors.
AB  - A distinctly new route for the design, modeling and electrical behavior of very
      short-channel (5-10 nm in channel length) nanowire field-effect transistors
      (FETs) has been presented. Essential elements of the approach entail a drain
      current determined by thermionic emission, but not by carrier mobility in the
      channel of the transistor. A basic understanding of the fundamental physics and
      the concepts of Schottky-barrier-based design for the proposed route have been
      described. Quantum confinement in the nanowire channel together with Schottky
      barrier tailing and temperature-dependent fluctuations of applied biases has been
      taken into account for the development of the model. Both current-voltage
      characteristics and transconductance of FETs have been studied. The calculated
      results are in near-quantitative agreement with the available experiments.
      Measured data show very diverse (e.g., exponential, linear, saturating, and non
      linear non-exponential non-saturating) nanowire transistor characteristics. The
      model explains these characteristics well and reveals a number of new transistor
      actions. It highlights the impacts of quantum confinement and Schottky contacts
      for these new transistor actions. It also quantifies the significant enhancement
      of the drain-source current and transconductance. With new findings thus
      achieved, suggestions for the realization of very high-performance, small
      diameter (preferably 2 nm), small-Schottky-barrier-height, high-operating
      temperature, ultra-short-channel-length, nanowire transistors have been made.
      Optimized design of these transistors has been suggested. And the range (in terms
      of device and technological parameters) of the proposed model has been
      elucidated. 

PMID- 24129341
TI  - Numerical processing in the human parietal cortex during experimental and natural
      conditions.
AB  - Human cognition is traditionally studied in experimental conditions wherein
      confounding complexities of the natural environment are intentionally eliminated.
      Thus, it remains unknown how a brain region involved in a particular experimental
      condition is engaged in natural conditions. Here we use electrocorticography to
      address this uncertainty in three participants implanted with intracranial
      electrodes and identify activations of neuronal populations within the
      intraparietal sulcus region during an experimental arithmetic condition. In a
      subsequent analysis, we report that the same intraparietal sulcus neural
      populations are activated when participants, engaged in social conversations,
      refer to objects with numerical content. Our prototype approach provides a means
      for both exploring human brain dynamics as they unfold in complex social settings
      and reconstructing natural experiences from recorded brain signals. 

PMID- 24129342
TI  - Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers.
AB  - Topical penetration of macromolecules into the skin is limited by their low
      permeability. Here, we report the use of a skin penetrating peptide, SPACE
      peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW:
      200-325kDa). The peptide was conjugated to phospholipids and used to prepare an
      ethosomal carrier system (~110nm diameter), encapsulating HA. The SPACE-ethosomal
      system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/-1.1-fold
      compared to PBS. The system also enhanced penetration of HA in human skin in
      vitro, penetrating deep into the epidermis and dermis in skin of both species. In
      vivo experiments performed using SKH1 hairless mice also confirmed increased
      dermal penetration of HA using the delivery system; a 5-fold enhancement in
      penetration was found compared to PBS control. Concentrations of HA in skin were
      about 1000-fold higher than those in blood; confirming the localized nature of HA
      delivery into skin. The SPACE-ethosomal delivery system provides a formulation
      for topical delivery of macromolecules that are otherwise difficult to deliver
      into the skin. 

PMID- 24129343
TI  - Genetic variants in DNA repair pathways are not associated with disease
      progression among multiple myeloma patients.
AB  - DNA damage induced by high dose melphalan and autologous transplantation is
      repaired by the nucleotide excision repair (NER) and base excision repair (BER)
      pathways. We evaluated the association between single nucleotide polymorphisms
      (SNPs) (n=311) in the NER and BER pathways and disease progression in 695
      multiple myeloma patients who underwent autologous transplantation. None of the
      SNPs were associated with disease progression. Pathway based analyses showed that
      the NER pathway had a borderline association with disease progression (p=0.09).
      These findings suggest that common variation in the NER and BER pathways do not
      substantially influence disease progression in multiple myeloma patients. 

PMID- 24129344
TI  - The clinical significance of cereblon expression in multiple myeloma.
AB  - Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma
      (MM). We demonstrate here that no patient with very low CRBN expression responded
      to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with
      pomalidomide and dexamethasone, CRBN levels predict for decreased response rates
      and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs.
      27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher
      CRBN levels can serve as a surrogate for low risk disease, our study demonstrates
      that low CRBN expression can predict resistance to IMiD monotherapy and is a
      predictive biomarker for survival outcomes. 

PMID- 24129347
TI  - Appraising iniparib, the PARP inhibitor that never was--what must we learn?
AB  - Several drugs targeting poly(ADP-ribose) polymerase (PARP) enzymes are under
      development. Responses have been observed in patients with germline mutations in
      BRCA1 and BRCA2, with further data supporting antitumour activity of PARP
      inhibitors in sporadic ovarian cancer. Strategies to identify other predictive
      biomarkers remain under investigation. Iniparib was purported to be a PARP
      inhibitor that showed promising results in randomized phase II trials in patients
      with triple-negative breast cancer. Negative results from a phase III study in
      this disease setting, however, tempered enthusiasm for this agent. Recently, data
      from in vitro experiments suggest that iniparib is not only structurally distinct
      from other described PARP inhibitors, but is also a poor inhibitor of PARP
      activity. In this context, the negative iniparib phase III data might have
      erroneously promulgated the notion that PARP inhibition is not an effective
      therapeutic strategy. Here, we scrutinize the development of iniparib from
      preclinical studies to registration trials, and identify and discuss the pitfalls
      in the development of anticancer drugs to prevent future late-stage trial
      failures. 

PMID- 24129349
TI  - Targeted therapies: treating advanced kidney cancer-miles to go before we sleep.

PMID- 24129354
TI  - New technology: nanotechnology targets cancer cells.

PMID- 24129355
TI  - Immunogenicity of heptavalent conjugate vaccine against Streptococcus pneumoniae
      in premature babies with low birth weight.
AB  - BACKGROUND: There are few studies about immunogenicity and safety of heptavalent
      pneumococcal-CRM197 conjugate vaccine (PCV7) in low birth weight infants.
      OBJECTIVE: Assessment of immunogenicity following administration of PCV7 in low
      birth weight children. METHODS: The PCV7 vaccine was administered to 60 infants
      divided into two groups: 23 children with birth weight <1000 g (Group I); and 37
      children with birth weight >=1000 g (Group II). Serum was collected four times.
      RESULTS: Birth weight of children included in the study ranged from 480 g to 2450
      g. The primary immunization caused an increase in the average concentration of
      antibodies for all serotypes in most of the participants, with no significant
      differences between the groups. However, there were some differences between
      various serotypes. Group serotypes 6B and 23F were the least immunogenic (>=0.35
      MUg/mL, Group I vs. Group II - 6B: 78.3% vs. 67,6% p = 0.371 and 23F: 87% vs.
      83.8% p = 0.738). Prior to the administration of a booster dose, a significant
      decrease in antibody titer was observed in all children. The last vaccination
      resulted in an increased concentration of antibodies in all children in both
      groups, and the results were significantly higher compared to those measured
      following administration of three doses of the vaccine. CONCLUSION: PCV7 is
      immunogenic in children with low, very low, and extremely low birth weight.
      Serotypes 6B and 23F were the least immunogenic, and serotype 14 proved to be the
      most immunogenic.

PMID- 24129356
TI  - Parallel array of nanochannels grafted with polymer-brushes-stabilized Au
      nanoparticles for flow-through catalysis.
AB  - Smart systems on the nanometer scale for continuous flow-through reaction present
      fascinating advantages in heterogeneous catalysis, in which a parallel array of
      straight nanochannels offers a platform with high surface area for assembling and
      stabilizing metallic nanoparticles working as catalysts. Herein we demonstrate a
      method for finely modifying the nanoporous anodic aluminum oxide (AAO), and
      further integration of nanoreactors. By using atomic transfer radical
      polymerization (ATRP), polymer brushes were successfully grafted on the inner
      wall of the nanochannels of the AAO membrane, followed by exchanging counter ions
      with a precursor for nanoparticles (NPs), and used as the template for deposition
      of well-defined Au NPs. The membrane was used as a functional nanochannel for
      novel flow-through catalysis. High catalytic performance and instantaneous
      separation of products from the reaction system was achieved in reduction of 4
      nitrophenol. 

PMID- 24129357
TI  - Superphobicity/philicity Janus fabrics with switchable, spontaneous, directional
      transport ability to water and oil fluids.
AB  - Herein we demonstrate that switchable, spontaneous, directional-transport ability
      to both water and oil fluids can be created on fabric materials through wet
      chemistry coating and successive UV irradiation treatment. When the fabric showed
      directional transport to a liquid, it prevented liquids of higher surface tension
      from penetration, but allowed liquids of lower surface tension to permeate, from
      either side. The directional transport ability can be switched from one fluid to
      another simply by heating the fabric at an elevated temperature and then re
      irradiating the fabric with UV light for required period of time. By attaching
      liquid drops vertically upwards to a horizontally-laid fabric, we further
      demonstrated that this novel directional fluid transport was an automatic process
      driven by surface property alone, irrespective of gravity's effect. This novel
      fabric may be useful for development of "smart" textiles and functional membranes
      for various applications. 

PMID- 24129358
TI  - Effects of an isocaloric healthy Nordic diet on ambulatory blood pressure in
      metabolic syndrome: a randomized SYSDIET sub-study.
AB  - BACKGROUND/OBJECTIVES: Dietary pattern is central in the prevention of
      hypertension and blood pressure (BP)-related diseases. A diet based on healthy
      Nordic foods may have a favourable impact on BP. The objective was to clarify
      whether a Nordic alternative for a healthy food pattern would have beneficial
      effects on ambulatory BP in subjects with metabolic syndrome (MetS).
      SUBJECTS/METHODS: In total, 37 subjects were randomized to either a healthy
      Nordic diet or a control diet. A healthy Nordic diet embraced whole grains,
      rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products
      of Nordic origin. The mean nutrient intake in the Nordic countries formed the
      control diet, embracing wheat products, dairy fat-based spread and a lower intake
      of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was
      monitored and 24-h urine was collected before and after 12 weeks of intervention.
      RESULTS: After 12 weeks, ambulatory diastolic BP (-4.4 mm Hg; P=0.001) and mean
      arterial pressure (-4.2 mm Hg; P=0.006) were lowered by the healthy Nordic diet
      compared with the control diet, whereas changes in ambulatory systolic BP did not
      differ significantly between diets (-3.5 mm Hg; P=0.122). Heart rate tended to be
      lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium
      excretions were unaffected by diets and consequently not associated with the
      healthy Nordic diet-induced lowering of BP. CONCLUSIONS: Consumption of Nordic
      varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory
      BP and mean arterial pressure in subjects with features of MetS during weight
      stable condition, suggesting beneficial effects of a healthy Nordic dietary
      pattern on ambulatory BP.

PMID- 24129359
TI  - Changes to dietary intake during a 12-week commercial web-based weight loss
      program: a randomized controlled trial.
AB  - BACKGROUND/OBJECTIVES: The primary aim of this secondary analysis was to compare
      changes in dietary intake among participants randomized to two versions of a 12
      week commercial web-based weight loss program (basic or enhanced) with a waiting
      list control. An additional investigation compared changes in dietary intake of
      successful participants (weight loss >=5%) with those not successful.
      SUBJECTS/METHODS: Dietary intake was assessed at baseline and 12 weeks using a
      validated 120-item semiquantitative food frequency questionnaire. Adults (n=268,
      60% female participants, body mass index 32.1 +/- 3.9) classified as plausible
      reporters of energy intake were included in the analyses. Analysis of covariance
      with baseline observations carried forward for drop-outs (n=38) was used.
      RESULTS: The basic and enhanced groups significantly increased their percentage
      of energy contribution from fruits and reduced energy-dense, nutrient-poor foods
      compared with controls (P<0.001). Successful participants (n=49) reported
      superior improvements in dietary intake including greater reductions in the mean
      daily energy intake (P<0.001), the percentage of energy from energy-dense,
      nutrient-poor foods (-12.0% E vs -4.3% E, P<0.001) and greater increases in the
      energy contribution from fruits (P<0.001), vegetables (P=0.003) and
      breads/cereals (P=0.02). CONCLUSIONS: Use of a commercial web-based weight loss
      program facilitated some improvements in the dietary intake. The enhanced web
      based tools appeared not to have generated greater improvements in reported
      dietary intake, compared with the basic or control groups. Those who achieved a
      weight loss of >=5% improved their dietary intake in line with the program
      recommendations and dietary guidelines. Further research to determine web-based
      components that may improve success and the reasons why programs are successful
      for some participants is required.

PMID- 24129360
TI  - Short sleep duration is associated with a lower mean satiety quotient in
      overweight and obese men.
AB  - We examined satiety quotient (SQ) and energy intake (EI) according to sleep
      duration, quality and timing. Seventy-five overweight/obese men (age: 41.1+/-5.8
      years; body mass index: 33.6+/-2.9 kg/m(2)) completed visual analogue scales for
      appetite sensations before, immediately after and every 10 minutes for 1 hour
      following a standardized breakfast. The mean SQ (primary outcome of the study)
      was calculated from four appetite sensations. The Pittsburgh Sleep Quality Index
      identified short-duration (<7 h/night) and 'recommended sleep duration' (?7
      h/night) sleepers, poor (score ?5)- and good (score <5)-quality sleepers and late
      (midpoint of sleep >0230 hours) and early (midpoint of sleep ?0230 hours)
      sleepers. A 3-day food record and buffet-style meal assessed the EI. Short
      duration sleepers had a lower mean SQ compared with recommended sleep duration
      sleepers (6.5+/-4.9 vs 8.8+/-4.3 mm/100 kcal; P=0.04). The mean SQ between poor
      and good (6.9+/-4.6 vs 8.7+/-4.6 mm/100 kcal; P=0.11) and that between early and
      late (8.99+/-5.10 vs 9.32+/-4.02 mm/100 kcal; P=0.78) sleepers were not
      significantly different. EI did not differ between the sleep groups. Thus, short
      duration sleepers had a lower mean SQ compared with recommended sleep duration
      sleepers. However, this did not coincide with an increased EI. 

PMID- 24129361
TI  - Nutritional status in patients with chronic pancreatitis.
AB  - OBJECTIVE: Chronic pancreatitis (CP) patients have an increased risk of
      malnutrition. Information about nutritional status of CP outpatients is scarce,
      and simple, sensitive methods to identify patients at risk are lacking. This
      explorative cross-sectional study was performed to survey the nutritional status
      of CP outpatients. SUBJECTS: Fifty patients with chronic or recurrent acute
      pancreatitis (RAP) had a nutritional assessment performed. Scores on nutritional
      screening tools and a quality of life questionnaire were assessed. General
      observations and relations between parameters were described. RESULTS: Thirty
      nine patients had CP and eleven patients had RAP. According to the nutritional
      screening tools, 28-50% of the patients had a moderate or high risk of
      malnutrition. All domains of the Short Form Health Survey were significantly
      lowered in CP patients (all P?0.001) compared with the Dutch norm values. A
      considerable number of patients scored below the 5th percentile on anthropometric
      measures. Mini Nutritional Assessment could not identify all patients with very
      low anthropometric scores. Substantial weight loss was not a sensitive indicator
      for functional impairment. CONCLUSION: CP outpatients are at risk of
      malnutrition. Currently used screening methods (for example, weight loss) are
      likely to be not sensitive enough to identify all patients with impaired body
      composition and restricted function. Therefore, some patients with objective
      decline in nutritional status will remain unidentified. An extended nutritional
      assessment is recommendable in CP patients.

PMID- 24129362
TI  - Assessment of hydration biomarkers including salivary osmolality during passive
      and active dehydration.
AB  - BACKGROUND/OBJECTIVES: Hydration state can be assessed via body mass change
      (BMDelta), serum and urine osmolality (Sosm, Uosm), urine-specific gravity (Usg)
      and urine volume (Uvol). As no hydration index has been shown to be valid in all
      circumstances, value exists in exploring novel biomarkers such as salivary
      osmolality (Vosm). Utilizing acute BMDelta as the reference standard, this
      research examined the efficacy of Sosm, Vosm, Uosm, Uvol and Usg, during passive
      (PAS) and active (ACT) heat exposure. SUBJECTS/METHODS: Twenty-three healthy men
      (age, 22+/-3 years; mass, 77.3+/-12.8 kg; height, 179.9+/-8.8cm; body fat, 10.6+/
      4.5%) completed two randomized 5-h dehydration trials (36+/-1  degrees C). During
      PAS, subjects sat quietly, and during ACT, participants cycled at 68+/-6% maximal
      heart rate. Investigators measured all biomarkers at each 1% BMDelta. RESULTS:
      Average mass loss during PAS was 1.4+/-0.3%, and 4.1+/-0.7% during ACT.
      Significant between-treatment differences at -1% BMDelta were observed for Sosm
      (PAS, 296+/-4; ACT, 301+/-4 mOsm/kg) and Uosm (PAS, 895+/-207; ACT, 661+/-192
      mOsm/kg). During PAS, only Uosm, Uvol and Usg increased significantly (-1 and -2%
      BMDelta versus baseline). During ACT, Vosm most effectively diagnosed dehydration
      ?2% (sensitivity=86%; specificity=91%), followed by Sosm (sensitivity=83%;
      specificity=83%). Reference change values were validated for Sosm, Usg and
      BMDelta. CONCLUSIONS: The efficacy of indices to detect dehydration ?2% differed
      across treatments. At rest (PAS), only urinary indices increased in concert with
      body water loss. During exercise (ACT), Sosm and Vosm exhibited the highest
      sensitivity and specificity. Sosm, Usg and BMDelta exhibited validity in serial
      measurements. These findings indicate hydration biomarkers should be selected by
      considering daily activities.

PMID- 24129363
TI  - Effects of Avena nuda L. on metabolic control and cardiovascular disease risk
      among Chinese patients with diabetes and meeting metabolic syndrome criteria:
      secondary analysis of a randomized clinical trial.
AB  - BACKGROUND/OBJECTIVES: Most patients with Type 2 diabetes mellitus(DM) also have
      metabolic syndrome (MetS), which is associated with an increased risk of coronary
      heart disease prevalence. Limited information is available on the effect and
      effective doses of oat intake with a structured dietary intervention in metabolic
      control and cardiovascular disease (CVD) risk prevention with the population who
      has Type 2 DM and meets the MetS criteria. SUBJECTS/METHODS: A total of 260 Type
      2 DM patients meeting MetS National Cholesterol Education Program Adult Treatment
      Panel III criteria were selected from 445 patients between 50 and 65 years of
      age, and they participated in a single-blinded, 30-day centralized management of
      a dietary program in China. Participants in the program were randomly assigned
      into one of the four groups: usual care group (control group, only basic health
      advice), diet group (systematic diet plans and intensive education), 50 g-organic
      naked oat with whole germ group (ONOG) and 100 g-organic naked oat with whole
      germ group (daily ONOG replacement boiled into porridge based on diet group). The
      primary outcomes were the relative changes in glycosylated hemoglobin (HbA1c) and
      insulin resistance after a 30-day intervention among the four groups. RESULTS:
      HbA1c decreased significantly with the increase in interventions (Ptrend<0.05).
      Similar results were also obtained in plasma glucose, serum lipid and
      hypersensitive C-reactive protein (hs-CRP). For the 100 g-ONOG group but not 50 g
      ONOG group, HbA1c and hs-CRP reduced significantly by 0.51% and 1.29 mg/l
      (P<0.05, vs diet group), respectively. The 100 g-ONOG group showed a reduction by
      0.22 U*mol/l(2) in insulin resistance, compared with the 50 g-ONOG group
      (P=0.039). CONCLUSIONS: Compared with diet alone or no diet, 50-100 g/day ONOG
      supplement to structured dietary intervention, at a dose of 100 g/day especially,
      contributes to the Type 2 DM patients meeting MetS criteria in their metabolic
      control and CVD risk prevention, with external factors being controlled.

PMID- 24129364
TI  - Determinants of fat-soluble vitamin status in patients aged 65 years and over.
AB  - In the elderly, malnutrition is highly prevalent and a major contributor to
      increased morbidity and mortality. We aimed to evaluate the fat-soluble vitamin
      status and potential determinants in patients >65 years of age. Serum vitamins A,
      D and E were determined by liquid chromatography in 166 patients. Gender, age,
      season, hospitalization, nutritional markers (albumin and cholesterol), acute
      phase reactants (ferritin and C-reactive protein) and renal function (creatinine
      and glomerular filtrate) were assessed as potential determinants. Prevalence of
      vitamin deficiency was highly variable, ranging from 0 (vitamin E/cholesterol
      ratio) to 94% (for vitamin D in hospitalized patients). Vitamin status did not
      differ according to gender, but age, season, hospitalization, a poor nutritional
      status and impaired renal function, and the presence of acute-phase response
      significantly affected serum levels of vitamin A, E and D. In conclusion, in
      subjects >65 years both demographic and clinical factors determined the fat
      soluble vitamin status. 

PMID- 24129365
TI  - Omega-3 fatty acids: a review of the effects on adiponectin and leptin and
      potential implications for obesity management.
AB  - An increase in adiposity is associated with altered levels of biologically active
      proteins. These include the hormones adiponectin and leptin. The marked change in
      circulating concentrations of these hormones in obesity has been associated with
      the development of insulin resistance and metabolic syndrome. Variations in
      dietary lipid consumption have also been shown to impact obesity. Specifically,
      omega-3 fatty acids have been correlated with the prevention of obesity and
      subsequent development of chronic disease sequalae. This review explores animal
      and human data relating to the effects of omega-3 fatty acids (marine lipids) on
      adiponectin and leptin, considering plausible mechanisms and potential
      implications for obesity management. Current evidence suggests a positive, dose
      dependent relationship between omega-3 fatty acid intake and circulating levels
      of adiponectin. In obese subjects, this may translate into a reduced risk of
      developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese
      subjects, omega-3 is observed to decrease circulating levels of leptin; however,
      omega-3-associated increases in leptin levels have been observed in obese
      subjects. This may pose benefits in the prevention of weight regain in these
      subjects following calorie restriction. 

PMID- 24129366
TI  - A critical pathway for the management of elderly inpatients with malnutrition:
      effects on serum insulin-like growth factor-I.
AB  - BACKGROUND: Several guidelines recommend systematic screening for malnutrition in
      elderly inpatients for early dietary intakes assessment and treatment, but data
      demonstrating the efficacy of such interventions are scarce. The aim of this
      study was to evaluate a critical medical pathway for the detection and management
      of malnutrition in elderly inpatients. METHODS: In a 3-month prospective
      controlled study, 694 recently admitted inpatients were assigned to an
      intervention group (critical medical pathway; n=465) or a standard care control
      group (n=229). Nutritional status was assessed at the time of admission with a
      Mini Nutritional Assessment. A renutrition program tailored to the initial
      dietary assessment results was applied in the intervention group. The efficacy of
      the program was verified by measuring the evolution of serum insulin-like growth
      factor 1 (IGF-I) between admission and 3 weeks later. RESULTS: In the
      intervention group at baseline, 23% were malnourished, 51% were at risk and 26%
      were eunourished. Serum IGF-I increased in the intervention group (from 84+/-45
      MUg/l to 95+/-50 MUg/l, P<0.0001; mean+/-s.d., n=209), but remained stable in the
      controls (from 79+/-43 MUg/l to 81+/-35 MUg/l, P=0.4; n=99), with a statistically
      significant between group difference (P<0.01). CONCLUSION: Early malnutrition
      assessment and targeted renutrition program in elderly inpatients were associated
      with an increase in serum IGF-I. It remains to be determined whether such
      variations are clinically relevant.

PMID- 24129367
TI  - Which values are important for patients during involuntary treatment? A
      qualitative study with psychiatric inpatients.
AB  - Involuntary hospital treatment is practised throughout the world. Providing
      appropriate treatment in this context is particularly challenging for mental
      health professionals, who frequently face ethical issues as they have to
      administer treatments in the absence of patient consent. We have explored the
      views of 59 psychiatric patients who had been involuntarily admitted to hospital
      treatment across England. Moral deliberation theory, developed in the field of
      clinical bioethics, was used to assess ethical issues. Interviews were audio
      recorded and transcribed verbatim, and analysed through thematic content
      analysis. We have detected a number of circumstances in the hospital that were
      perceived as potentially conflictual by patients. We have established which
      patient values should be considered by staff when deliberating on ethically
      controversial issues in these circumstances. Patients regarded as important
      having freedom of choice and the feeling of being safe during their stay in the
      hospital. Patients also valued non-paternalistic and respectful behaviour from
      staff. Consideration of patient values in moral deliberation is important to
      manage ethical conflicts. Even in the ethically challenging context of
      involuntary treatment, there are possibilities to increase patient freedoms,
      enhance their sense of safety and convey respect. 

PMID- 24129368
TI  - CD8 T-cell activation is associated with lipodystrophy and visceral fat
      accumulation in antiretroviral therapy-treated virologically suppressed HIV
      infected patients.
AB  - OBJECTIVE: HIV-infected patients receiving antiretroviral treatment frequently
      accumulate fat at the abdominal level. It is unknown whether T-cell activation
      and immune phenotypes are associated with fat accumulation. Thus, the aim of the
      study was to search for an association between the presence of clinical
      lipodystrophy (LD), visceral and subcutaneous abdominal adipose tissue amount
      (VAT and SAT), and peripheral T-cell immune phenotypes. DESIGN: Cross-sectional
      study including 87 HIV-infected antiretroviral therapy-treated virologically
      suppressed and immune-reconstituted patients. METHODS: The patients were
      evaluated for clinical LD, VAT, SAT, homeostasis model of insulin resistance, and
      coronary artery calcium score (>10). T-cell activation (CD8/CD38),
      differentiation (CD4/CD8/CCR7/CD45RA), and expression/activation of the
      interleukin-7 (IL-7)/IL-7R system (CD4/CD8/CD127, IL-7, and CD4/CD8/pStat-5) were
      assessed by cytometry. RESULTS: In multivariable analyses, CD8 T-cell activation
      (CD38) was associated with lipoatrophy and central fat accumulation
      (respectively, beta = 5.63, P = 0.005, and beta = 4.19, P = 0.020). This was also
      the case for IL-7R expressing CD8+ T cells (CD127+) for lipoatrophy beta = 12.8,
      P = 0.003, and for central fat accumulation beta = 9.45, P = 0.016. CD8+ T-cell
      activation was also associated with VAT/total adipose tissue (beta = 0.01, P =
      0.002) and SAT/VAT ratios (beta = -0.014, P = 0.015). As expected, VAT/total
      adipose tissue was an independent risk factor for homeostasis model of insulin
      resistance (r = 0.364, P = 0.028) and cardiovascular risk (coronary artery
      calcium, r = 0.406, P = 0.002). CONCLUSIONS: CD8+ T-cell activation was
      associated with LD and the relative amount of VAT in antiretroviral therapy
      controlled, virologically suppressed, HIV-infected patients. We propose that CD8
      activation may be involved in the accumulation of central fat frequently observed
      in these patients, with resulting increased cardiometabolic risk.

PMID- 24129369
TI  - Cost-effectiveness of newer antiretroviral drugs in treatment-experienced
      patients with multidrug-resistant HIV disease.
AB  - OBJECTIVE: Newer antiretroviral drugs provide substantial benefits but are
      expensive. The cost-effectiveness of using antiretroviral drugs in combination
      for patients with multidrug-resistant HIV disease was determined. DESIGN: A
      cohort state-transition model was built representing treatment-experienced
      patients with low CD4 counts, high viral load levels, and multidrug-resistant
      virus. The effectiveness of newer drugs (those approved in 2005 or later) was
      estimated from published randomized trials. Other parameters were estimated from
      a randomized trial and from the literature. The model had a lifetime time horizon
      and used the perspective of an ideal insurer in the United States. The
      interventions were combination antiretroviral therapy, consisting of 2 newer
      drugs and 1 conventional drug, compared with 3 conventional drugs. Outcome
      measures were life-years, quality-adjusted life-years (QALYs), costs, and
      incremental cost-effectiveness. RESULTS: Substituting newer antiretroviral drugs
      increased expected survival by 3.9 years in advanced HIV disease. The incremental
      cost-effectiveness ratio of newer, compared with conventional, antiretroviral
      drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only
      one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on
      assumptions about efficacy. Substituting 3 newer drugs cost $105,956 to
      $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were
      not discontinued. CONCLUSIONS: In treatment-experienced patients with advanced
      HIV disease, use of newer antiretroviral agents can be cost-effective, given a
      cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained.
      Newer antiretroviral agents should be used in carefully selected patients for
      whom less expensive options are clearly inferior.

PMID- 24129370
TI  - Retention in care is more strongly associated with viral suppression in HIV
      infected patients with lower versus higher CD4 counts.
AB  - BACKGROUND: Retention in care is important for all HIV-infected patients, but may
      be more important for people with advanced HIV disease. We evaluated whether the
      association between retention in care and viral suppression differed by HIV
      disease severity. METHODS: A repeated cross-sectional analysis (2006-2011)
      involving 35,433 adults at 18 US HIV clinics. Multivariable logistic regression
      models examined associations between retention measures [Health Resources and
      Services Administration (HRSA) retention measure, 6-month gap, and 3-month visit
      constancy] and viral suppression (HIV-1 RNA <= 400 copies/mL) for HIV disease
      severity groups defined by CD4 counts: <= 200, 201-350, 351-500, and >500 cells
      per cubic millimeter. RESULTS: Overall, patients met the HRSA measure in 84% of
      person-years, did not have a 6-month gap in 76%, and had visits in all 4 quarters
      in 37%; patients achieved viral suppression in 72% of person-years. The
      association between retention in care and viral suppression differed by disease
      severity, and was strongest for patients with lower CD4 counts: <= 200 [adjusted
      odds ratio (AOR) = 2.33, 95% confidence interval (CI): 2.16 to 2.51], 201-350
      (AOR = 1.96, CI: 1.81 to 2.12), 351-500 (AOR = 1.65, CI: 1.53 to 1.78), and >500
      cells per cubic millimeter (AOR = 1.22, CI: 1.14 to 1.30) using the HRSA
      retention measure as a representative example. CONCLUSIONS: This is one of the
      first studies to report the impact of HIV disease severity on retention in care
      and viral suppression, demonstrating that retention in care is more strongly
      associated with viral suppression in patients with lower CD4 counts. These
      results have important implications for improving the health of patients with
      advanced HIV disease and for test and treat approaches to HIV prevention.

PMID- 24129371
TI  - From a mononuclear Ni(II) precursor to antiferromagnetically coupled trinuclear
      double-stranded helicates.
AB  - Reaction of the mononuclear Ni(II) complex [Ni{2-Py(6-NH2)NHC(S)NP(S)(OiPr)2}2]
      with different salicylaldehydes leads to new antiferromagnetically coupled
      trinuclear double-stranded helicates , where Ni(II) metal ions are coordinated by
      two bis-anionic thiourea ligands and two deprotonated molecules of the
      corresponding aldehyde.

PMID- 24129373
TI  - CANTABmobile and its misleading promotion.

PMID- 24129372
TI  - Enhanced single molecule fluorescence and reduced observation volumes on
      nanoporous gold (NPG) films.
AB  - We report single molecule fluorescence studies on nanoporous gold films. We
      observed dramatically enhanced intensities in individual immobilized fluorophores
      and reduced effective observation volumes in the nanopores. The enhanced
      localized plasmon field existing in the "nanovoid" regions can be visualized from
      the overlaid mapping image derived from surface reflectance and fluorescence
      emission. 

PMID- 24129374
TI  - PACE trial authors' reply to letter by Kindlon.

PMID- 24129375
TI  - All people with dementia need accurate assessment and ongoing support.

PMID- 24129376
TI  - Alistair Burns and 51 colleagues reply to David Le Couteur and colleagues.

PMID- 24129377
TI  - Providing adequate and practical descriptions in surgical trials.

PMID- 24129378
TI  - Deprived areas will lose out with proposed new capitation formula.

PMID- 24129379
TI  - Hospital standardised mortality rates should not be used to make interhospital
      comparisons.

PMID- 24129380
TI  - Claims about NHS deficiencies without robust data undermine trust.

PMID- 24129381
TI  - Medical incident reporting needs a global online system.

PMID- 24129382
TI  - Alliance Boots accused of avoiding over L1bn in UK tax.

PMID- 24129383
TI  - Australasian College of Physicians sacks its ethics committee.

PMID- 24129384
TI  - London's health services need radical change, says NHS England.

PMID- 24129385
TI  - Competition rules over merger has cost NHS L1.8m, BMJ probe shows.

PMID- 24129386
TI  - United Nations is sued over cholera epidemic in Haiti.

PMID- 24129387
TI  - A terahertz photomixer based on plasmonic nanoantennas coupled to a graphene
      emitter.
AB  - We propose the concept of a graphene-based nanoantenna-enhanced photomixer to
      realize wideband-tunable terahertz (THz) frequency generation. When two laser
      beams are focused on the graphene nanoemitter of a planar field-emission diode,
      THz current oscillations can be created at the emitter tip through the optical
      heterodyne. Graphene's optical transparency allows suitably designed plasmonic
      nanoantennas to boost the mixing of laser radiation at the emitter tip,
      significantly increasing the overall produced photomixing current. The THz wave
      generated at the graphene emitter is then coupled to a loading circuit, thanks to
      the THz wave confinement in the graphene nanostructures. Our design is ideally
      suited for THz sources that may be tuned from DC to 10 THz by simply shifting the
      frequency offset of two pumping lasers. 

PMID- 24129388
TI  - Observation of T2-like coherent optical phonons in epitaxial Ge2Sb2Te5/GaSb(001)
      films.
AB  - The phonon spectrum of Ge2Sb2Te5 is a signature of its crystallographic structure
      and underlies the phase transition process used in memory applications. Epitaxial
      materials allow coherent optical phonons to be studied in femtosecond anisotropic
      reflectance measurements. A dominant phonon mode with frequency of 3.4 THz has
      been observed in epitaxial Ge2Sb2Te5 grown on GaSb(001). The dependence of signal
      strength upon pump and probe polarization is described by a theory of transient
      stimulated Raman scattering that accounts for the symmetry of the
      crystallographic structure through use of the Raman tensor. The 3.4 THz mode has
      the character of the 3 dimensional T2 mode expected for the O(h) point group,
      confirming that the underlying crystallographic structure is cubic. New modes are
      observed in both Ge2Sb2Te5 and GaSb after application of large pump fluences, and
      are interpreted as 1 and 2 dimensional modes associated with segregation of Sb.

PMID- 24129389
TI  - Epidemiological study for personal risk factors and quality of life related to
      Dupuytren's disease in a mountain village of Japan.
AB  - BACKGROUND: This study investigated the etiology, personal risk factors, and
      quality of life related to Dupuytren's disease among residents of a mountain
      village in Japan. METHODS: Medical examinations were conducted of 401 adult
      residents (163 men, 238 women; average age of 66.7 years, range 40-92) of a
      mountain village in Japan. All had completed a self-administered questionnaire
      including items for gender, weight, height, dominant hand, occupation, history of
      diabetes mellitus, and frequency of smoking tobacco and drinking alcohol, in
      addition to EuroQol-5-Dimensions-3-level Japanese version. Blood samples were
      collected and assessed for biochemical markers related to Dupuytren's disease.
      The Dupuytren's disease diagnosis was based on clinical signs. Meyerding's
      classification was used to ascertain the disease severity. After examining
      background data and physical examination data related to Dupuytren's disease, we
      evaluated the association of Dupuytren's disease with those factors using
      univariate and logistic regression analysis. RESULTS: Dupuytren's disease was
      diagnosed in 28 subjects (7.0%). Univariate analysis revealed associations of
      age, male gender, occupation, history of diabetes mellitus, and alcohol intake
      with Dupuytren's disease. Logistic regression analysis after adjustment for age
      revealed a significant association between Dupuytren's disease and male gender,
      occupation, and history of alcohol intake. No significant difference was found
      between Dupuytren's disease patients and participants without this disease in the
      scoring and visual analog scale of EuroQol. No relation was found in scoring, the
      visual analog scale of EuroQol, or grading of Meyerding's classification in
      participants with Dupuytren's disease. CONCLUSION: This cross-sectional study
      revealed Dupuytren's disease in 7.0% of 401 subjects among the general population
      of a mountain village in Japan. The prevalence is higher with age and is
      apparently associated with male gender, occupation and alcohol intake. Risk
      factors associated with Dupuytren's disease were identified as age, male gender,
      occupation, and alcohol consumption habits.

PMID- 24129390
TI  - Earthworms facilitate carbon sequestration through unequal amplification of
      carbon stabilization compared with mineralization.
AB  - A recent review concluded that earthworm presence increases CO2 emissions by 33%
      but does not affect soil organic carbon stocks. However, the findings are
      controversial and raise new questions. Here we hypothesize that neither an
      increase in CO2 emission nor in stabilized carbon would entirely reflect the
      earthworms' contribution to net carbon sequestration. We show how two widespread
      earthworm invaders affect net carbon sequestration through impacts on the balance
      of carbon mineralization and carbon stabilization. Earthworms accelerate carbon
      activation and induce unequal amplification of carbon stabilization compared with
      carbon mineralization, which generates an earthworm-mediated 'carbon trap'. We
      introduce the new concept of sequestration quotient to quantify the unequal
      processes. The patterns of CO2 emission and net carbon sequestration are
      predictable by comparing sequestration quotient values between treatments with
      and without earthworms. This study clarifies an ecological mechanism by which
      earthworms may regulate the terrestrial carbon sink.

PMID- 24129391
TI  - Optical analysis of human eye using electromagnetic wave theory.
AB  - We present a two-dimensional electromagnetic analysis of light propagation
      through the human eye to examine the eye's optical properties. The
      electromagnetic approach has intriguing advantages over the conventional and
      frequently implemented ray optics analysis. The chromatic, spherical, and coma
      aberrations and the intensity of the focused light at the retina are computed in
      this work via full-wave analysis. We also investigate the effects of the cornea's
      and lens's curved structures on the focusing mechanism. The focal length and
      chromatic and spherical aberrations are observed to change owing to age-related
      refractive index variation in the lens. In addition, the effects of the lens and
      curvatures of the human eye on focusing are analyzed. Consequently, for both
      young and old human eye lenses, the differences due to the aberration variations,
      curvature surfaces, and gradient index are explored by the wave approach. The
      intensity distributions on the retina for both on- and off-axis illumination are
      calculated. A strong correlation between the locations of the nerve fibers and
      the intensity distribution is confirmed. On the basis of the findings, we can
      conclude that visual impairment due to deterioration of the human eye structure
      is more dramatic than that due to aging.

PMID- 24129392
TI  - Molecular characterization of Als1, an acetohydroxyacid synthase mutation
      conferring resistance to sulfonylurea herbicides in soybean.
AB  - KEY MESSAGE: The AHAS gene family in soybean was characterized. The locus Als1
      for sulfonylurea resistance was mapped and the resistant allele was characterized
      at the molecular level. Sulfonylurea (SU) resistance in soybean is controlled by
      Als1, a semi-dominant allele obtained by EMS mutagenesis over the cultivar
      Williams 82. The overall objective of this research was to map Als1 in the
      soybean genome and to determine the nucleotidic changes conferring resistance to
      SU. Four nucleotide sequences (GmAhas1-4) showing high homology with the
      Arabidopsis thaliana acetohydroxyacid synthase (AHAS, EC 4.1.3.18) gene sequence
      were identified by in silico analysis, PCR-amplified from the SU-resistant line
      BTK323STS and sequenced. Expression analysis showed that GmAhas1, located on
      chromosome 4 by in silico analysis, is the most expressed sequence in true
      leaves. F2:3 families derived from the cross between susceptible and resistant
      lines were evaluated for SU resistance. Mapping results indicate that the locus
      als1 is located on chromosome 4. Sequence comparison of GmAhas1 between BTK323STS
      and Williams 82 showed a single nucleotide change from cytosine to thymine at
      position 532. This transversion generates an amino acid change from proline to
      serine at position 197 (A. thaliana nomenclature) of the AHAS catalytic subunit.
      An allele-specific marker developed for the GmAhas1 mutant sequence cosegregated
      with SU resistance in the F2 population. Taking together, the mapping, expression
      and sequencing results indicate that the GmAhas1 sequence corresponds to the Als1
      gene sequence controlling SU resistance in soybean. The molecular breeding tools
      described herein create the basis to speed up the identification of new mutations
      in soybean AHAS leading to enhanced levels of resistance to SU or to other
      families of AHAS inhibitor herbicides.

PMID- 24129393
TI  - Mutations in chicory FEH genes are statistically associated with enhanced
      resistance to post-harvest inulin depolymerization.
AB  - KEY MESSAGE: Nucleotidic polymorphisms were identified in fructan exohydrolases
      genes which are statistically associated with enhanced susceptibility to post
      harvest inulin depolymerization. Industrial chicory (Cichorium intybus L.) root
      is the main commercial source of inulin, a linear fructose polymer used as
      dietary fiber. Post-harvest, inulin is depolymerized into fructose which
      drastically increases processing cost. To identify genetic variations associated
      with enhanced susceptibility to post-harvest inulin depolymerization and related
      free sugars content increase, we used a candidate-gene approach focused on inulin
      and sucrose synthesis and degradation genes, all members of the family 32 of
      glycoside hydrolases (GH32). Polymorphism in these genes was first investigated
      by carrying out EcoTILLING on two groups of chicory breeding lines exhibiting
      contrasted response to post-harvest inulin depolymerization. This allowed the
      identification of polymorphisms significantly associated with depolymerization in
      three fructan exohydrolase genes (FEH). This association was confirmed on a wider
      panel of 116 unrelated families in which the FEH polymorphism explained 35 % of
      the post-harvest variance for inulin content, 36 % of variance for sucrose
      content, 18 % for inulin degree of polymerization, 23 % for free fructose content
      and 22 % for free glucose content. These polymorphisms were associated with
      significant post-harvest changes of inulin content, inulin chain length and free
      sugars content.

PMID- 24129394
TI  - Chiral olefin-sulfoxide as ligands for rhodium-catalyzed asymmetric conjugate
      addition of arylboronic acids to unsaturated esters.
AB  - An efficient rhodium/olefin-sulfoxide catalyzed asymmetric conjugate addition of
      organoboronic acids to various unsaturated esters has been developed, where 2
      methoxy-1-naphthyl sulfinyl functionalized olefin ligands have been shown to be
      highly effective, and are especially applicable to unsaturated methyl esters with
      up to 99% yield and 91% ee. 

PMID- 24129395
TI  - Trends in incidence of, and mortality from, cervical lesions in Ireland: baseline
      data for future evaluation of the national cervical screening programme.
AB  - AIM: To investigate incidence and mortality trends for cervical lesions in
      Ireland in the period 1994-2008. METHODS: We used data from the National Cancer
      Registry, Ireland and national death registration data to calculate age
      standardised rates for the periods of interest. We used standardised rate ratios
      to test whether incidence was associated with socio-demographic variables and
      used Joinpoint to examine trends by morphology grouping. RESULTS: Incidence of
      cervical cancer and cervical intraepithelial neoplasia (CIN3) rose over the
      period 1994-2008. The annual percentage change for cervical cancer was 1.8% and
      that for CIN3 was 3.8%. Women resident in the most deprived areas had invasive
      cervical cancer incidence almost twice as high as those resident in the least
      deprived areas (standardised rate ratio (SRR)=1.8). Comparing incidence in
      Ireland to England and Wales, Northern Ireland and Scotland in the three years
      2005-2007, the SRRs (other areas vs. Ireland) were 0.70, 0.88 and 0.84
      respectively. Cervical cancer rates have fallen in these countries in the same
      period that there is a rise demonstrated in Ireland. CONCLUSION: Incidence rates
      of cervical cancer rose in Ireland steadily, albeit modestly, during 1994-2008,
      most likely due to long-term changes in patterns of sexual behaviour and
      contraceptive use. A more pronounced rise in CIN3 rates point to considerable
      levels of opportunistic screening during this period. Mortality rates have
      changed little over the past four decades, in contrast to trends in countries
      with well-organised screening programmes.

PMID- 24129396
TI  - Determinants of reversibility of beta-cell dysfunction in response to short-term
      intensive insulin therapy in patients with early type 2 diabetes.
AB  - Short-term intensive insulin therapy (IIT) can improve pancreatic beta-cell
      function when administered early in the course of type 2 diabetes mellitus
      (T2DM). However, the degree of improvement in response to this therapy varies
      between patients. Thus, we sought to characterize the determinants of improvement
      in beta-cell function in response to short-term IIT in early T2DM. Sixty-three
      patients with mean 3.0 +/- 2.1 yr duration of T2DM and Hb A1c of 6.8 +/- 0.8%
      underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin
      aspart, with oral glucose tolerance test administered at baseline and 1 day post
      IIT. beta-Cell function before and after IIT was assessed by Insulin Secretion
      Sensitivity Index-2 (ISSI-2). Reversibility of beta-cell dysfunction was defined
      as percentage change in ISSI-2 of >=25%. Overall, the study population
      experienced an increase in ISSI-2 from baseline to post-IIT (P = 0.01), with one
      third of participants achieving >=25% improvement in ISSI-2. Compared with their
      peers, those with increases in ISSI-2 of >=25% had greater decrements in fasting
      glucose (P < 0.0001), Hb A1c (P = 0.001), ALT (P = 0.04), AST (P = 0.02), and
      HOMA-IR (P < 0.0001). On logistical regression analysis, baseline Hb A1c (OR =
      2.83, 95% CI 1.16-6.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004
      0.16, P = 0.001) emerged as independent predictors of reversibility of beta-cell
      dysfunction. Indeed, reversibility of beta-cell dysfunction was achieved in only
      those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion,
      decline in HOMA-IR may be a key determinant of improvement of beta-cell function
      in response to short-term IIT, suggesting a fundamental contribution of insulin
      resistance to the reversible component of beta-cell dysfunction in early T2DM. 

PMID- 24129397
TI  - Sestrin 3 regulation in type 2 diabetic patients and its influence on metabolism
      and differentiation in skeletal muscle.
AB  - In mammals, the sestrin family is composed of three stress-responsive genes.
      Ablation of sestrin in Drosophila attenuates longevity, which is accompanied by
      increased S6K phosphorylation and decreased AMPK phosphorylation. Nevertheless,
      the metabolic role of sestrins in mammals is not comprehensively understood. We
      characterized the expression of individual sestrin family members and determined
      their role in vastus lateralis muscle biopsies from participants with normal
      glucose tolerance (NGT) or type 2 diabetes (T2D). Expression of sestrin 1 or
      sestrin 2 mRNA was unaltered between the NGT and T2D participants. Conversely,
      sestrin 3 mRNA was increased in T2D patients and correlated with fasting plasma
      glucose, 2-h postprandial plasma glucose and HbA1c. A trend for increased sestrin
      3 protein was observed in T2D patients. In human primary myotubes, sestrin 3 mRNA
      increased during differentiation, and this response was unaltered in T2D-derived
      myotubes. Long-term treatment of myotubes with insulin or AICAR decreased sestrin
      3 mRNA. Exposure of myotubes to the reactive oxygen species H2O2 increased mRNA
      expression of sestrin 1 and 2, whereas sestrin 3 was unaltered. siRNA-mediated
      silencing of sestrin 3 in myotubes was without effect on insulin-stimulated
      glucose incorporation into glycogen or AICAR-stimulated palmitate oxidation.
      These results provide evidence against sestrin 3 in the direct control of glucose
      or lipid metabolism in human skeletal muscle. However, siRNA-mediated sestrin 3
      gene silencing in myotubes increased myostatin expression. Collectively, our
      results indicate sestrin 3 is upregulated in T2D and could influence skeletal
      muscle differentiation without altering glucose and lipid metabolism. 

PMID- 24129398
TI  - Adiponectin inhibits oxidative/nitrative stress during myocardial ischemia and
      reperfusion via PKA signaling.
AB  - The cardioprotective effects of adiponectin (APN) against myocardial
      ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the
      mechanisms mediating intracellular APN signaling remains incomplete. We recently
      demonstrate the antioxidant/antinitrative effects of APN are not dependent on
      AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN,
      with uncertain relevance to APN cardiac protection. The current study determined
      whether the antioxidative/antinitrative effect of APN is mediated by PKA.
      Administration of APN (2 MUg/g) 10 min before reperfusion significantly enhanced
      cardiac PKA activity, reduced oxidative stress, and decreased infarct size.
      Knockdown of cardiac PKA expression (PKA-KD) by intramyocardial injection of PKA
      siRNAs (>70% suppression) significantly inhibited APN cardioprotection determined
      by cardiac apoptosis, infarct size, and cardiac function. Moreover, PKA-KD
      virtually abolished the suppressive effect of APN on MI/R-induced NADPH oxidase
      overexpression and superoxide overproduction and partially inhibited the effect
      of APN on nitrative protein modification in MI/R heart. Mechanistically, APN
      significantly inhibited MI/R-induced IKK/IkappaB phosphorylation and NF-kappaB
      activation, which were blocked in PKA-KD heart. Finally, the PKA-mediated
      antioxidant/antinitrative and cardioprotective effects of APN are intact in AMPK
      deficient mice, suggesting that there is no cross talk between AMPK and PKA
      signaling in APN cardioprotection. Collectively, we demonstrate for the first
      time that APN inhibits oxidative/nitrative stress during MI/R via PKA-dependent
      NF-kappaB inhibition. 

PMID- 24129400
TI  - Cationic cyanine dyes: impact of symmetry-breaking on optical absorption and
      third-order polarizabilities.
AB  - A systematic study is carried out to find the exact crossover point from
      symmetric to asymmetric configurations (symmetry-breaking) in a series of
      cationic cyanine dyes. Hybrid density functional with varying exact-exchange
      admixture has been used to understand the impact of HF exchange both in the gas
      phase and in the presence of dielectric medium. This approach provides a basis
      for understanding the electronic structure and photophysical properties of
      cyanine dyes. The crossover points predicted using this method are in good
      agreement with the experiment. The SAC-CI method is used to evaluate the lowest
      S0 -> S1 transition energies in the gas phase. These transitions are preferably
      dominated by the promotion of an electron from HOMO -> LUMO. The average static
      third-order polarizabilities, [gamma], are obtained within the three-state model
      approximation. The analysis showed that for symmetric cyanines, the calculated
      [gamma] values are large and negative, mainly originated from the large S0 -> S1
      transition moments and small S0 -> S1 transition energies. For asymmetric
      cyanines, the [gamma] values are positive and mainly originate from the large
      change in the ground and first excited state dipole moments. However, both
      configurations do not include contributions from the two-photon absorption.
      Further, the localization of charge densities in the HOMO and LUMO indicates that
      the symmetric and asymmetric cyanines act as promising materials for molecular
      wires and molecular switches which are fundamental building blocks for molecular
      electronic devices.

PMID- 24129399
TI  - Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver
      specific SREBP-1c Tg mice fed high-fat and high-fructose diet.
AB  - Because the renin-angiotensin-aldosterone system has been implicated in the
      development of insulin resistance and promotion of fibrosis in some tissues, such
      as the vasculature, we examined the effect of eplerenone, a selective
      mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis
      (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in
      humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active
      form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and
      fructose diet (HFFD) as the animal model in the present study. When wild-type
      (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12
      wk, body weight and epididymal fat weight increased in both groups with an
      elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin
      resistance were also observed. Adipose tissue hypertrophy and macrophage
      infiltration with crown-like structure formation were also noted in mice fed
      HFFD. Interestingly, the changes noted in both genotypes fed HFFD were
      significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the
      histological features of NASH in the liver, including macrovesicular steatosis
      and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent
      fibrotic changes. Eplerenone effectively ameliorated these histological
      abnormalities. Moreover, the direct suppressive effects of eplerenone on
      lipopolysaccharide-induced TNFalpha production in the presence and absence of
      aldosterone were observed in primary-cultured Kupffer cells and bone marrow
      derived macrophages. These results indicated that eplerenone prevented the
      development of NASH and metabolic abnormalities in mice by inhibiting
      inflammatory responses in both Kupffer cells and macrophages. 

PMID- 24129401
TI  - LipoxinA4 attenuates myocardial ischemia reperfusion injury via a mechanism
      related to downregulation of GRP-78 and caspase-12 in rats.
AB  - This study aims to determine the effect of Lipoxin (LX)A4 on myocardial ischemia
      reperfusion injury (MIRI) in rats and the related molecular mechanisms. Male SD
      rats were divided into six groups. The sham operation groups (groups C1, C2) were
      injected with 2 ml/kg normal saline before and after coronary artery threading,
      respectively. The MIRI group (groups I/R1, I/R2) were injected with normal saline
      before and after MIRI, respectively. The LXA4 groups (groups LX1, LX2) were
      injected with LXA4 before and after MIRI treatment, respectively. The hematoxylin
      eosin staining and ultrastructural changes of cardiac muscle were observed. The
      serum levels of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)
      alpha and cardiac troponin I (cTnI) were measured before open-chest operation and
      at the end of the experiment. The mRNA and protein levels of GRP-78 and caspase
      12 were determined in each group. The myocardial cell apoptosis, myeloperoxidase
      (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) contents were
      detected. The mRNA and protein levels of GRP-78 and caspase-12, the apoptosis,
      the serum IL-1beta, IL-6, IL-10, TNF-alpha, and cTnI concentrations, MPO, SOD,
      MDA contents were significantly increased in groups I/R1, I/R2, LX1, and LX2
      compared with those in groups C1 and C2 (P < 0.05). The mRNA and protein
      expression levels of GRP-78 and caspase-12 in groups LX1 and LX2 were lower than
      those in groups I/R1 and I/R2. Compared with group I/R1 and I/R2, the myocardial
      neutrophil infiltration and ultrastructure damage were significantly less in
      groups LX1 and LX2. GRP-78 and IL-10 are expressed both extracellularly and
      intracellularly, but are mainly expressed in the cytoplasms. In the absence of
      MIRI, LXA4 has no detectable effect on GRP-78 and caspase-12 expression. Before
      and after MIRI, application of LXA4 significantly inhibits neutrophil activation,
      and attenuates myocardial inflammatory injury and oxidative stress. LXA4
      downregulates the mRNA and protein expression of GRP-78 and caspase-12. LXA4
      could play a role in myocardial protection via a mechanism related to
      downregulation of GRP-78 and caspase-12, and inhibition of apoptosis.

PMID- 24129402
TI  - Identifying overlapping communities as well as hubs and outliers via nonnegative
      matrix factorization.
AB  - Community detection is important for understanding networks. Previous studies
      observed that communities are not necessarily disjoint and might overlap. It is
      also agreed that some outlier vertices participate in no community, and some hubs
      in a community might take more important roles than others. Each of these facts
      has been independently addressed in previous work. But there is no algorithm, to
      our knowledge, that can identify these three structures altogether. To overcome
      this limitation, we propose a novel model where vertices are measured by their
      centrality in communities, and define the identification of overlapping
      communities, hubs, and outliers as an optimization problem, calculated by
      nonnegative matrix factorization. We test this method on various real networks,
      and compare it with several competing algorithms. The experimental results not
      only demonstrate its ability of identifying overlapping communities, hubs, and
      outliers, but also validate its superior performance in terms of clustering
      quality. 

PMID- 24129403
TI  - The influence of paper coating content on room temperature sintering of silver
      nanoparticle ink.
AB  - The resistance of inkjet printed lines using a silver nanoparticle based ink can
      be very dependent on the substrate. A very large difference in resistivity was
      observed for tracks printed on paper substrates with aluminum oxide based
      coatings compared to silica based coatings. Silica based coatings are often
      cationized with polymers using chloride as a counter ion. It is suggested that
      the precipitation of silver salts is the cause of the high resistivity, since
      papers pretreated with salt solutions containing ions that precipitate silver
      salts gave a high resistance. Silver nitrate has a high solubility and paper
      pretreated with nitrate ions gave a low resistivity without sintering. The
      results obtained show that, by choosing the correct type of paper substrate, it
      is possible to manufacture printed structures, such as interconnects on paper,
      without the need for, or at least to reduce the need for, post-print sintering.
      This phenomenon is, of course, ink specific. Inks without or with a low silver
      ion content are not expected to behave in this manner. In some sensor
      applications, a high resistivity is desired and, by using the correct combination
      of ink and paper, these types of sensors can be facilitated. 

PMID- 24129404
TI  - A multicomponent cascade reaction for the synthesis of novel
      chromenopyranpyrazole scaffolds.
AB  - A catalyst, solvent, work-up and column free synthesis of chromenopyranpyrazoles
      via multicomponent cascade reaction has been achieved with high
      stereoselectivity. This novel reaction creates two N-C, two C-C and one O-C bonds
      through a domino process for the construction of three new rings and three
      contiguous stereogenic centers. 

PMID- 24129405
TI  - Tsc1 deficiency-mediated mTOR hyperactivation in vascular endothelial cells
      causes angiogenesis defects and embryonic lethality.
AB  - This is a study on the role of tuberous sclerosis complex1 (TSC1) mutation and
      mTOR activation in endothelial cells during angiogenic and embryonic development.
      Past studies had shown that Tsc1/Tsc2 mutant genes lead to overactivation of mTOR
      in the regulating pathways in developing fetus. We used conditional Cre-loxp gene
      knockout approach to delete Tsc1 in mice's endothelial cells in our experimental
      models. Similarly, activation of mTOR signaling in endothelial cells of these
      embryos (Tie2-Cre/Tsc1(-/-)) was found. Majority of Tie2-Cre/Tsc1(-/-) embryos
      died at embryonic day 14.5 in utero. Cardiovascular defects, subcutaneous edema
      and hemorrhage were present among them. Whole-mount immunostaining in these
      embryos revealed a disorganized vascular network, defective sprouting of vessels
      in yolk sac and thickening of the labyrinth layer in the placenta. A thinner
      ventricular wall with disorganized trabeculae was present in the hearts of Tie2
      Cre/Tsc1(-/-) embryos. Endothelial cells in Tsc1-deficient mice showed defective
      mitochondrial and endoplasmic reticular morphology, but no significant change was
      observed in cell junctions. The mutant embryos displayed significantly reduced
      cell proliferation, increased apoptosis and disturbed expression of angiogenic
      factors. A cohort of mice was treated prenatally with mTOR inhibitor rapamycin.
      The offspring of these mutant mice survived up to 22 days after birth. It was
      concluded that physiological TSC1-mTOR signaling in endothelial cells is crucial
      for vascular development and embryogenesis. We postulated that disruption of
      normal angiogenic pathways through hyperactive mTOR signaling maybe the mechanism
      that lead to deranged vascular pathogenesis in the tuberous sclerosis complex. 

PMID- 24129407
TI  - Duration of disease may predict response to infliximab in pediatric ulcerative
      colitis.
AB  - BACKGROUND: Infliximab (IFX) is an established treatment modality for moderate to
      severe pediatric ulcerative colitis (UC). The purpose of this study was to
      identify clinical and laboratory parameters, which predict response to IFX in
      pediatric UC defined by colectomy as the primary outcome measure. Postsurgical
      complications were examined as well. METHODS: A retrospective chart review was
      performed on children younger than 19 years who received IFX therapy at Texas
      Children's Hospital, Houston, Texas for the treatment of UC from January 2005 to
      April 2012. Demographics, laboratory data, clinical subtype, duration of disease,
      transfusion requirement, number of IFX infusions, concurrent medications, and
      postoperative complication with regard to IFX exposure were examined. RESULTS:
      Forty-seven patients (22 male and 25 female; average age at diagnosis: 11.4 y)
      received IFX. Twenty-six (55.3%) required colectomy, 20 (42.6%) of which occurred
      within a year of therapy initiation. Disease duration <20 months before IFX
      initiation, increased the likelihood of a colectomy within a year [OR: 3.8 (95%
      CI, 1.6-13.3), P=0.044]. Blood transfusion requirement before IFX was associated
      with higher rates of colectomy within a year [OR: 9.78 (95% CI, 2.2-43.3),
      P=0.0028]. Preoperative exposure to IFX within 8 weeks did not significantly
      increase postoperative complications (P=0.26). Serum albumin levels at diagnosis
      did not predict colectomy. CONCLUSIONS: Shorter disease duration and need for
      blood transfusion may be useful indicators of limited response to IFX in
      pediatric UC.

PMID- 24129406
TI  - Transcriptional regulation in pluripotent stem cells by methyl CpG-binding
      protein 2 (MeCP2).
AB  - Rett syndrome (RTT) is one of the most prevalent female mental disorders. De novo
      mutations in methyl CpG-binding protein 2 (MeCP2) are a major cause of RTT. MeCP2
      regulates gene expression as a transcription regulator as well as through long
      range chromatin interaction. Because MeCP2 is present on the X chromosome, RTT is
      manifested in an X-linked dominant manner. Investigation using murine MeCP2 null
      models and post-mortem human brain tissues has contributed to understanding the
      molecular and physiological function of MeCP2. In addition, RTT models using
      human induced pluripotent stem cells derived from RTT patients (RTT-iPSCs)
      provide novel resources to elucidate the regulatory mechanism of MeCP2.
      Previously, we obtained clones of female RTT-iPSCs that express either wild-type
      or mutant MECP2 due to the inactivation of one X chromosome. Reactivation of the
      X chromosome also allowed us to have RTT-iPSCs that express both wild-type and
      mutant MECP2. Using these unique pluripotent stem cells, we investigated the
      regulation of gene expression by MeCP2 in pluripotent stem cells by transcriptome
      analysis. We found that MeCP2 regulates genes encoding mitochondrial membrane
      proteins. In addition, loss of function in MeCP2 results in de-repression of
      genes on the inactive X chromosome. Furthermore, we showed that each mutation in
      MECP2 affects a partly different set of genes. These studies suggest that
      fundamental cellular physiology is affected by mutations in MECP2 from early
      development, and that a therapeutic approach targeting to unique forms of mutant
      MeCP2 is needed. 

PMID- 24129409
TI  - Moral dilemmas faced by hospitals in time of war: the Rambam Medical Center
      during the second Lebanon war.
AB  - Rambam Medical Center, the only tertiary care center and largest hospital in
      northern Israel, was subjected to continuous rocket attacks in 2006. This extreme
      situation posed serious and unprecedented ethical dilemmas to the hospital
      management. An ambiguous situation arose that required routine patient care in a
      tertiary modern hospital together with implementation of emergency measures while
      under direct fire. The physicians responsible for hospital management at that
      time share some of the moral dilemmas faced, the policy they chose to follow, and
      offer a retrospective critical reflection in this paper. The hospital's first
      priority was defined as delivery of emergency surgical and medical services to
      the wounded from the battlefields and home front, while concomitantly providing
      the civilian population with all elective medical and surgical services. The need
      for acute medical service was even more apparent as the situation of conflict led
      to closure of many ambulatory clinics, while urgent or planned medical care such
      as open heart surgery and chemotherapy continued. The hospital management took
      actions to minimize risks to patients, staff, and visitors during the ongoing
      attacks. Wards were relocated to unused underground spaces and corridors. However
      due to the shortage of shielded spaces, not all wards and patients could be
      relocated to safer areas. Modern warfare will most likely continue to involve
      civilian populations and institutes, blurring the division between peaceful high
      tech medicine and the rough battlefront. Hospitals in high war-risk areas must be
      prepared to function and deliver treatment while under fire or facing similar
      threats. 

PMID- 24129410
TI  - Sustained cardiac remodeling after a short-term very low calorie diet in type 2
      diabetes mellitus patients.
AB  - A very low calorie diet (VLCD) results in cardiac remodeling and improved
      diastolic function. It is unknown how long these effects sustain after
      reintroduction of a regular diet. We aimed to assess the long-term effects of
      initial weight loss by VLCD on cardiac dimensions and function in type 2 diabetes
      mellitus (T2DM) patients. Fourteen insulin-dependent T2DM patients (mean +/- SEM:
      age 53 +/- 2 years; BMI 35 +/- 1 kg/m(2)) were treated by a VLCD (450 kcal/day)
      during 16 weeks. Cardiac function and myocardial triglyceride (TG) content were
      measured by magnetic resonance imaging and spectroscopy at baseline, after a 16
      week VLCD and after 14 months of follow-up on a regular diet. BMI decreased from
      35 +/- 1 to 28 +/- 1 kg/m(2) after VLCD and increased again to 32 +/- 1 kg/m(2)
      at 18 months (both P < 0.05 vs. baseline). Left ventricular (LV) end-diastolic
      volume index increased after the 16-week VLCD (80 +/- 3 to 89 +/- 4 ml/m(2), P <
      0.05) and remained increased after follow-up (90 +/- 3 ml/m(2); P < 0.05 vs.
      baseline) at comparable filling pressures. The improvement in LV diastolic
      function after the 16-week VLCD, was sustained at 18 months [early (E)/atrial (A)
      diastolic filling phase ratio: 0.96 +/- 0.07 (baseline); 1.12 +/- 0.06 (after
      VLCD); 1.06 +/- 0.07 (18 months, P < 0.05 vs. baseline)]. Myocardial TG content
      decreased after the 16-week VLCD [0.74 (0.41-1.10) to 0.45 (0.31-0.54) %, P <
      0.05], but returned to baseline levels at 18 months [0.76 (0.65-1.32) %]. Weight
      reduction by a 16-week VLCD in T2DM patients results in sustained cardiac
      remodeling and improved diastolic function after 14 months of follow-up, despite
      weight regain on a regular diet.

PMID- 24129411
TI  - Importance of molecular genetic analysis in the diagnosis and classification of
      congenital hypothyroidism.

PMID- 24129412
TI  - Real-time in vivo imaging of invasive- and biomaterial-associated bacterial
      infections using fluorescently labelled vancomycin.
AB  - Invasive and biomaterial-associated infections in humans are often difficult to
      diagnose and treat. Here, guided by recent advances in clinically relevant
      optical imaging technologies, we explore the use of fluorescently labelled
      vancomycin (vanco-800CW) to specifically target and detect infections caused by
      Gram-positive bacteria. The application potential of vanco-800CW for real-time in
      vivo imaging of bacterial infections is assessed in a mouse myositis model and a
      human post-mortem implant model. We show that vanco-800CW can specifically detect
      Gram-positive bacterial infections in our mouse myositis model, discriminate
      bacterial infections from sterile inflammation in vivo and detect biomaterial
      associated infections in the lower leg of a human cadaver. We conclude that vanco
      800CW has a high potential for enhanced non-invasive diagnosis of infections with
      Gram-positive bacteria and is a promising candidate for early-phase clinical
      trials. 

PMID- 24129414
TI  - Folic acid conjugated self-assembled layered double hydroxide nanoparticles for
      high-efficacy-targeted drug delivery.
AB  - Enhanced selectivity and efficacy is important for advanced drug delivery.
      Herein, a novel type of folic acid conjugated self-assembled layered double
      hydroxide nanoparticles is reported. These nanoparticles have a drug loading
      capacity of 27 wt% and are able to enter cell nuclei and dramatically improve the
      efficacy of MTX. 

PMID- 24129413
TI  - Genome-wide expression profiling of human lymphoblastoid cell lines implicates
      integrin beta-3 in the mode of action of antidepressants.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for
      major depression. However, the link between inhibition of serotonin reuptake and
      remission from depression remains controversial: in spite of the rapid onset of
      serotonin reuptake inhibition, remission from depression takes several weeks,
      presumably reflecting synaptogenesis/neurogenesis and neuronal rewiring. We
      compared genome-wide expression profiles of human lymphoblastoid cell lines from
      unrelated individuals following treatment with 1 MUM paroxetine for 21 days with
      untreated control cells and examined which genes and microRNAs (miRNAs) showed
      the most profound and consistent expression changes. ITGB3, coding for integrin
      beta-3, showed the most consistent altered expression (1.92-fold increase, P=7.5
      * 10(-8)) following chronic paroxetine exposure. Using genome-wide miRNA arrays,
      we observed a corresponding decrease in the expression of two miRNAs, miR-221 and
      miR-222, both predicted to target ITGB3. ITGB3 is crucial for the activity of the
      serotonin transporter (SERT), the drug target of SSRIs. Moreover, it is
      presumably required for the neuronal guidance activity of CHL1, whose expression
      was formerly identified as a tentative SSRI response biomarker. Further genes
      whose expression was significantly modulated by chronic paroxetine are also
      implicated in neurogenesis. Surprisingly, the expression of SERT or serotonin
      receptors was not modified. Our findings implicate ITGB3 in the mode of action of
      SSRI antidepressants and provide a novel link between CHL1 and the SERT. Our
      observations suggest that SSRIs may relieve depression primarily by promoting
      neuronal synaptogenesis/neurogenesis rather than by modulating serotonin
      neurotransmission per se.

PMID- 24129415
TI  - Palladium-catalyzed Suzuki-Miyaura coupling of aryl sulfamates with arylboronic
      acids.
AB  - Readily available NHC-Pd(II)-Mp complexes 2 showed efficient catalytic activity
      toward the Suzuki-Miyaura coupling of aryl sulfamates with arylboronic acids or
      potassium phenyltrifluoroborate, giving the expected coupling products in good to
      high yields. It should be noted that this is the first example so far of the
      phosphine-free, NHC-Pd(II) complexes catalyzed Suzuki-Miyaura coupling of aryl
      sulfamates with arylboronic acids.

PMID- 24129416
TI  - Cytoskeleton: Autophagy and ciliogenesis come together.

PMID- 24129417
TI  - Cell cycle: Making an early decision.

PMID- 24129419
TI  - Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell
      death.
AB  - Receptor-interacting protein 1 (RIP1) kinase has emerged as a key upstream
      regulator that controls inflammatory signalling as well as the activation of
      multiple cell death pathways, including apoptosis and necroptosis. The ability of
      RIP1 to modulate these key cellular events is tightly controlled by
      ubiquitylation, deubiquitylation and the interaction of RIP1 with a class of
      ubiquitin receptors. The modification of RIP1 may thus provide a unique
      'ubiquitin code' that determines whether a cell activates nuclear factor-kappaB
      (NF-kappaB) to promote inflammatory signalling or induces cell death by apoptosis
      or necroptosis. Targeting RIP1 might be a novel therapeutic strategy for the
      treatment of both acute and chronic human diseases. 

PMID- 24129420
TI  - Long-term outcomes (>5-year follow-up) with porcine acellular dermal matrix
      (Permacol) in incisional hernias at risk for infection.
AB  - PURPOSE: We reviewed retrospectively all patients undergoing abdominal wall
      reconstruction using porcine acellular dermal matrix (PADM) from 2004 to 2008
      with follow-up assessment in 2012. Technique, short-term (infection, seroma,
      wound dehiscence), and long-term (mesh infection, recurrence) complications, and
      hernia recurrences were evaluated by physician examination >=5 years
      postoperatively. RESULTS: 56 patients at high risk for infection had elective
      operation; nine had non-elective operation for complications of prior incisional
      hernia/hernia repair. Operations were clean, clean-contaminated, contaminated, or
      grossly infected in 49, 32, 12, and 6%, respectively. Techniques of repair
      included 10 onlay (six reinforced primary closures, four bridging patches), 47
      sublay (20 reinforced primary closures, 27 bridging patches), six inlay, and two
      sandwich (sublay and onlay). Early complications (<=30 days postoperatively)
      occurred in 19 of the 65 patients (29%), including two prosthetic dehiscences
      from fascial attachment, 13 wound infections, and 4 seromas. After a mean follow
      up of >=5 years in 59 of 65 patients, physician-reported incidences of infection
      requiring removal of mesh or hernia recurrence were 25 and 66%, respectively.
      Hernia recurrence occurred in 12 of 26 (46%) patients with a reinforced repair
      and 27 of 33 (82%) with patched repairs. Mesh infection occurred in 7 of 24
      patients with sublay patch and in 4 of 19 sublay reinforcement. The greatest
      recurrence rate was in contaminated (71%) and grossly infected wounds (100%),
      while recurrence rate was 63% in clean and 63% in clean-contaminated wounds.
      CONCLUSIONS: At >=5 years of follow-up, use of PADM as a bioprosthesis in ventral
      hernia in high-risk patients is unreliable as a definitive repair in the majority
      of patients, but may provide satisfactory outcomes in some patients.

PMID- 24129421
TI  - Quality of life change in elderly patients undergoing open inguinal hernia
      repair.
AB  - PURPOSE: A growing proportion of inguinal hernia patients are at least 65 years
      old. Assessing operational benefits versus risks in this group of elderly
      patients merits research. METHODS: Patients in two prospective trials (1:n = 134,
      89 elderly; 2:n = 398, 70 elderly) completed RAND-36 questionnaires
      preoperatively (response rate 100 and 98.5 %, respectively) and at 3 (98.5 %) or
      12 months (89.6 %) after open inguinal hernia repair. In both groups,
      preoperative and postoperative quality of life data were statistically compared
      within age categories. Quality of life change was compared between age
      categories. Immediate complications were recorded. RESULTS: The dimensions
      physical functioning and pain improved significantly in the elderly and under 65
      year-olds. Role functioning/physical and social functioning showed improvement as
      well, but less constantly. No statistical difference in complication rates was
      found across age groups. CONCLUSION: Inguinal hernia surgery improves physical
      and social dimensions of quality of life among elderly and under 65-year-olds
      similarly.

PMID- 24129422
TI  - Seasonal air quality profile of size-segregated aerosols in the ambient air of a
      central Indian region.
AB  - Seasonal distribution trends of size-segregated aerosols i.e. submicron (PM1),
      fine (PM2.5) and coarse (PM2.5-10) and their relationship with meteorological
      variables employing correlation analysis were studied in the ambient air of
      central India from July 2009 to June 2010. The annual mean concentrations of PM1,
      PM2.5 and PM2.5-10 were found to be 65.7, 135.0 and 118.5 MUg m(-3),
      respectively. The annual mean PM2.5 concentration is three times higher than the
      National Ambient Air Quality Standards of India (NAAQS). Higher concentrations of
      PM1, PM2.5 and PM2.5-10 were found during winter due to enormous biomass burning
      especially during night time due to the use of combustible goods like fire wood
      and dung cake in the open space by the peoples to keep themselves warm and lower
      concentrations were observed during monsoon when there were high precipitations.
      PM2.5 showed high positive correlation with PM1 (r = 0.69) and moderate
      correlation with PM2.5-10 indicating that variation in PM2.5 mass is governed by
      the variation in PM1 mass or vice versa. 

PMID- 24129423
TI  - [Interdisciplinary approach in a patient with IgG4-associated Mikulicz's
      disease].
AB  - The clinical picture of enlarged submandibular gland and/or enlarged lacrimal
      gland often leads to difficulties in differential diagnostics. From the
      perspective of rheumatology Sjogren's syndrome should be excluded especially in
      patients who complained of xerophthalmia and xerostomia for longer than 3 months.
      In this article the authors report the case of a patient who presented to clarify
      swelling of the submandibular gland and xerostomia. In close cooperation with
      rheumatologists, otolaryngologists and pathologists the diagnosis of IgG4
      associated sialoadenitis (IgG4-associated Mikulicz's disease) could be reached. 

PMID- 24129424
TI  - [O'Dell reloaded: Do we use TNF inhibitors too early?].

PMID- 24129425
TI  - [ANCA-associated vasculitis and malignancy : current evidence for cause and
      consequence relationships].

PMID- 24129428
TI  - Metal-free molecular junctions on ITO via amino-silane binding-towards
      optoelectronic molecular junctions.
AB  - Light control over currents in molecular junctions is desirable as a non-contact
      input with high spectral and spatial resolution provided by the photonic input
      and the molecular electronics element, respectively. Expanding the study of
      molecular junctions to non-metallic transparent substrates, such as indium tin
      oxide (ITO), is vital for the observation of molecular optoelectronic effects.
      Non-metallic electrodes are expected to decrease the probability of quenching of
      molecular photo-excited states, light-induced plasmonic effects, or significant
      electrode expansion under visible light. We have developed micron-sized, metal
      free, optically addressable ITO molecular junctions with a conductive polymer
      serving as the counter-electrode. The electrical transport was shown to be
      dominated by the nature of the self-assembled monolayer (SAM). The use of amino
      silane (APTMS) as the chemical binding scheme to ITO was found to be significant
      in determining the transport properties of the junctions. APTMS allows high
      junction yields and the formation of dense molecular layers preventing electrical
      short. However, polar amino-silane binding to the ITO significantly decreased the
      conductance compared to thiol-bound SAMs, and caused tilted geometry and disorder
      in the molecular layer. As the effect of the molecular structure on transport
      properties is clearly observed in our junctions, such metal-free junctions are
      suitable for characterizing the optoelectronic properties of molecular junctions.

PMID- 24129427
TI  - Post-chemoradiation anastomotic recurrence in locally advanced rectal cancer: no
      increased risk associated with distal margin.
AB  - BACKGROUND AND PURPOSE: Anastomotic recurrence after radical sphincter-preserving
      surgery preceded by neoadjuvant therapy in locally advanced rectal cancer is an
      uncommon event that merits further assessment. The aim of this study is to
      analyze the effect of preoperative chemoradiation on the risk of anastomotic
      recurrence. Based on the initial extension of the tumor, we analyzed whether the
      distal surgical section was calculated through the virtual initial extension of
      the rectal tumor. PATIENTS AND METHODS: Eligible patients with locally advanced
      rectal cancer were offered preoperative chemoradiation, sphincter sparing surgery
      and intraoperative radiation therapy boost. RESULTS: 180 patients were treated
      with anterior resection (40 %), low anterior resection (45.6 %) and ultra-low
      anterior resection (14.4 %). With a median follow-up of 41.1 months (0.36-143
      months), anastomotic recurrence was diagnosed in 9 patients (5 %). There was no
      statistical correlation with downstaging (T or N), downsizing effects, or with
      distance from the lower limit of the residual lesion to the distal margin.
      Virtual intratumoral surgical section was speculated in 44 patients (3 developed
      anastomotic recurrence; 6.8 vs 4.8 %, p = 0.482). CONCLUSION: Anastomotic
      recurrence in patients with rectal cancer treated with neoadjuvant chemoradiation
      is an infrequent event. Virtual intratumoral surgical sections followed by
      anastomosis do not contribute to an excessive risk of recurrence. Our findings
      encourage the development of policies for preservation of the ano-rectal complex
      in rectal cancer patients.

PMID- 24129426
TI  - Guidelines for biomarker testing in metastatic melanoma: a National Consensus of
      the Spanish Society of Pathology and the Spanish Society of Medical Oncology.
AB  - This consensus statement, conceived as a joint initiative of the Spanish Society
      of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM), makes
      diagnostic and treatment recommendations for the management of patients with
      advanced or metastatic melanoma based on the current scientific evidence on
      biomarker use. This document thus provides an opportunity to improve healthcare
      efficiency and resource use, which will benefit these patients. Based on the data
      available so far, this expert group recommends routinely testing patients with
      metastatic melanoma for BRAF mutation status, as the result affects the
      subsequent therapeutic management of these patients. The analysis of genetic
      alterations in KIT may be reasonable in patients with primary tumours in acral or
      mucosal sites or on chronically sun-exposed skin, in an advanced condition, but
      not in patients with other types of melanomas. This panel believes that testing
      for other genetic alterations, such as NRAS mutation status in patients not
      carrying BRAF mutations, GNAQ/GNA11 mutational analysis or genetic alterations in
      PTEN, is not currently indicated as routine clinical practice, because the
      results do not influence treatment planning in these patients at the present
      time. Other important issues addressed in this document are the organisational
      requirements and quality controls needed for proper testing of these biomarkers,
      and the legal implications to be borne in mind. 

PMID- 24129430
TI  - Delineation of PIGV mutation spectrum and associated phenotypes in
      hyperphosphatasia with mental retardation syndrome.
AB  - Three different genes of the glycosylphosphatidylinositol anchor synthesis
      pathway, PIGV, PIGO, and PGAP2, have recently been implicated in
      hyperphosphatasia-mental retardation syndrome (HPMRS), also known as Mabry
      syndrome, a rare autosomal recessive form of intellectual disability. The aim of
      this study was to delineate the PIGV mutation spectrum as well as the associated
      phenotypic spectrum in a cohort of 16 individuals diagnosed with HPMRS on the
      basis of intellectual disability and elevated serum alkaline phosphate as minimal
      diagnostic criteria. All PIGV exons and intronic boundaries were sequenced in 16
      individuals. Biallelic PIGV mutations were identified in 8 of 16 unrelated
      families with HPMRS. The most frequent mutation detected in about 80% of affected
      families including the cases reported here is the c.1022C>A PIGV mutation, which
      was found in both the homozygous as well as the heterozygous state. Four further
      mutations found in this study (c. 176T>G, c.53G>A, c.905T>C, and c.1405C>T) are
      novel. Our findings in the largest reported cohort to date significantly extend
      the range of reported manifestations associated with PIGV mutations and
      demonstrate that the severe end of the clinical spectrum presents as a multiple
      congenital malformation syndrome with a high frequency of Hirschsprung disease,
      vesicoureteral, and renal anomalies as well as anorectal malformations. PIGV
      mutations are the major cause of HPMRS, which displays a broad clinical
      variability regarding associated malformations and growth patterns. Severe
      developmental delays, particular facial anomalies, brachytelephalangy, and
      hyperphosphatasia are consistently found in PIGV-positive individuals. 

PMID- 24129432
TI  - Genome-wide patterns of identity-by-descent sharing in the French Canadian
      founder population.
AB  - In genetics the ability to accurately describe the familial relationships among a
      group of individuals can be very useful. Recent statistical tools succeeded in
      assessing the degree of relatedness up to 6-7 generations with good power using
      dense genome-wide single-nucleotide polymorphism data to estimate the extent of
      identity-by-descent (IBD) sharing. It is therefore important to describe genome
      wide patterns of IBD sharing for more remote and complex relatedness between
      individuals, such as that observed in a founder population like Quebec, Canada.
      Taking advantage of the extended genealogical records of the French Canadian
      founder population, we first compared different tools to identify regions of IBD
      in order to best describe genome-wide IBD sharing and its correlation with
      genealogical characteristics. Results showed that the extent of IBD sharing
      identified with FastIBD correlates best with relatedness measured using
      genealogical data. Total length of IBD sharing explained 85% of the genealogical
      kinship's variance. In addition, we observed significantly higher sharing in
      pairs of individuals with at least one inbred ancestor compared with those
      without any. Furthermore, patterns of IBD sharing and average sharing were
      different across regional populations, consistent with the settlement history of
      Quebec. Our results suggest that, as expected, the complex relatedness present in
      founder populations is reflected in patterns of IBD sharing. Using these
      patterns, it is thus possible to gain insight on the types of distant
      relationships in a sample from a founder population like Quebec. 

PMID- 24129431
TI  - Homozygous missense and nonsense mutations in BMPR1B cause acromesomelic
      chondrodysplasia-type Grebe.
AB  - Acromesomelic chondrodysplasias (ACDs) are characterized by disproportionate
      shortening of the appendicular skeleton, predominantly affecting the middle
      (forearms and forelegs) and distal segments (hands and feet). Here, we present
      two consanguineous families with missense (c.157T>C, p.(C53R)) or nonsense
      (c.657G>A, p.(W219*)) mutations in BMPR1B. Homozygous affected individuals show
      clinical and radiographic findings consistent with ACD-type Grebe. Functional
      analysis of the missense mutation C53R revealed that the mutated receptor was
      partially located at the cell membrane. In contrast to the wild-type receptor,
      C53R mutation hindered the activation of the receptor by its ligand GDF5, as
      shown by reporter gene assay. Further, overexpression of the C53R mutation in an
      in vitro chondrogenesis assay showed no effect on cell differentiation,
      indicating a loss of function. The nonsense mutation (c.657G>A, p.(W219*))
      introduces a premature stop codon, which is predicted to be subject to nonsense
      mediated mRNA decay, causing reduced protein translation of the mutant allele. A
      loss-of-function effect of both mutations causing recessive ACD-type Grebe is
      further supported by the mild brachydactyly or even non-penetrance of these
      mutations observed in the heterozygous parents. In contrast, dominant-negative
      BMPR1B mutations described previously are associated with autosomal-dominant
      brachydactyly-type A2. 

PMID- 24129433
TI  - Meiotic outcomes of three-way translocations ascertained in cleavage-stage
      embryos: refinement of reproductive risks and implications for PGD.
AB  - Our study provides an analysis of the outcome of meiotic segregation of three-way
      translocations in cleavage-stage embryos and the accuracy and limitations of
      preimplantation genetic diagnosis (PGD) using the fluorescence in situ
      hybridization technique. We propose a general model for estimating reproductive
      risks for carriers of this class of complex chromosome rearrangement. The data
      presented describe six cycles for four couples where one partner has a three-way
      translocation. For male heterozygotes, 27.6% of embryos were consistent with 3:3
      alternate segregation resulting in a normal or balanced translocation chromosome
      complement; 41.4% were consistent with 3:3 adjacent segregation of the
      translocations, comprising 6.9% reflecting adjacent-1 and 34.5% adjacent-2
      segregation; 24.1% were consistent with 4:2 nondisjunction; none showed 5:1 or
      6:0 segregation; the probable mode could not be ascertained for 6.9% of embryos
      due to complex mosaicism or nucleus fragmentation. The test accuracy for male
      heterozygotes was estimated to be 93.1% with 100% sensitivity and 75%
      specificity. With 72.4% prevalence, the predictive value was estimated to be
      91.3% for an abnormal test result and 100% for a normal test result. Two of four
      couples had a healthy baby following PGD. The proportion of normal/balanced
      embryo could be significantly less for female heterozygotes, and our model
      indicates that this could be detrimental to the effectiveness of PGD. A 20% risk
      of live-born offspring with an unbalanced translocation is generally accepted,
      largely based on the obstetric history of female heterozygotes; we suggest that a
      3% risk may be more appropriate for male carriers. 

PMID- 24129434
TI  - Life insurance: genomic stratification and risk classification.
AB  - With the development and increasing accessibility of new genomic tools such as
      next-generation sequencing, genome-wide association studies, and genomic
      stratification models, the debate on genetic discrimination in the context of
      life insurance became even more complex, requiring a review of current practices
      and the exploration of new scenarios. In this perspective, a multidisciplinary
      group of international experts representing different interests revisited the
      genetics and life insurance debate during a 2-day symposium 'Life insurance:
      breast cancer research and genetic risk prediction seminar' held in Quebec City,
      Canada on 24 and 25 September 2012. Having reviewed the current legal, social,
      and ethical issues on the use of genomic information in the context of life
      insurance, the Expert Group identified four main questions: (1) Have recent
      developments in genomics and related sciences changed the contours of the
      genetics and life insurance debate? (2) Are genomic results obtained in a
      research context relevant for life insurance underwriting? (3) Should predictive
      risk assessment and risk stratification models based on genomic data also be used
      for life insurance underwriting? (4) What positive actions could stakeholders in
      the debate take to alleviate concerns over the use of genomic information by life
      insurance underwriters? This paper presents a summary of the discussions and the
      specific action items recommended by the Expert Group. 

PMID- 24129435
TI  - Site-specific methylation of placental HSD11B2 gene promoter is related to
      intrauterine growth restriction.
AB  - Intrauterine growth restriction (IUGR) is associated with detrimental effects on
      neurodevelopmental progress in childhood and higher risk of degenerative diseases
      in adulthood. Placental 11beta-hydroxysteroid dehydrogenase (HSD11B2) is a key
      gene involved in glucocorticoid metabolism, which in turn seems to be related to
      fetal growth impairment. As reduction of placental HSD11B2 gene expression has
      been associated with reduced human fetal growth, and methylation of HSD11B2 gene
      promoter has been shown to have an important role in HSD11B2 gene repression, we
      seek to investigate the relationship between IUGR and HSD11B2 gene promoter
      methylation in human placentas. We found that methylation levels of all studied
      CpG sites were significantly higher in IUGR newborns than those in controls.
      Further, methylation levels of the first and the third CpG sites were inversely
      associated with measures of fetal growth (birth weight and ponderal index). In
      addition, consistent with the above negative correlation, methylation levels of
      the first and the third CpG sites were inversely associated with HSD11B2 gene
      expression. These results together show a link between the site-specific
      methylation of placental HSD11B2 promoter and the development of IUGR. 

PMID- 24129436
TI  - Looking for CDKN1C enhancers.

PMID- 24129437
TI  - Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18,
      and MYT1L genes.
AB  - Obesity is a common but highly, clinically, and genetically heterogeneous
      disease. Deletion of the terminal region of the short arm of chromosome 2 is rare
      and has been reported in about 13 patients in the literature often associated
      with a Prader-Willi-like phenotype. We report on five unrelated patients with
      2p25 deletion of paternal origin presenting with early-onset obesity,
      hyperphagia, intellectual deficiency, and behavioural difficulties. Among these
      patients, three had de novo pure 2pter deletions, one presented with a paternal
      derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the
      last patient presented with an interstitial 2p25 deletion. The size of the
      deletions was characterized by SNP array or array-CGH and was confirmed by
      fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3
      deletion with a minimal critical region estimated at 1.97 Mb and encompassing
      seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The
      fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and
      MYT1L genes. Paternal origin of the deletion was determined by genotyping using
      microsatellite markers. Analysis of the genes encompassed in the deleted region
      led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved
      in early-onset obesity. In addition, intellectual deficiency and behavioural
      troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes.
      Finally, we discuss the parent-of-origin of the deletion. 

PMID- 24129439
TI  - A search for varying fundamental constants using hertz-level frequency
      measurements of cold CH molecules.
AB  - Many modern theories predict that the fundamental constants depend on time,
      position or the local density of matter. Here we develop a spectroscopic method
      for pulsed beams of cold molecules, and use it to measure the frequencies of
      microwave transitions in CH with accuracy down to 3 Hz. By comparing these
      frequencies with those measured from sources of CH in the Milky Way, we test the
      hypothesis that fundamental constants may differ between the high- and low
      density environments of the Earth and the interstellar medium. For the fine
      structure constant we find Deltaalpha/alpha=(0.3 +/- 1.1) * 10-7, the strongest
      limit to date on such a variation of alpha. For the electron-to-proton mass ratio
      we find DeltaMU/MU=(-0.7 +/- 2.2) * 10-7. We suggest how dedicated astrophysical
      measurements can improve these constraints further and can also constrain
      temporal variation of the constants.

PMID- 24129441
TI  - Noncompetitive retrieval practice causes retrieval-induced forgetting in cued
      recall but not in recognition.
AB  - Retrieving a subset of learned items can lead to the forgetting of related items.
      Such retrieval-induced forgetting (RIF) can be explained by the inhibition of
      irrelevant items in order to overcome retrieval competition when the target item
      is retrieved. According to the retrieval inhibition account, such retrieval
      competition is a necessary condition for RIF. However, research has indicated
      that noncompetitive retrieval practice can also cause RIF by strengthening cue
      item associations. According to the strength-dependent competition account, the
      strengthened items interfere with the retrieval of weaker items, resulting in
      impaired recall of weaker items in the final memory test. The aim of this study
      was to replicate RIF caused by noncompetitive retrieval practice and to determine
      whether this forgetting is also observed in recognition tests. In the context of
      RIF, it has been assumed that recognition tests circumvent interference and,
      therefore, should not be sensitive to forgetting due to strength-dependent
      competition. However, this has not been empirically tested, and it has been
      suggested that participants may reinstate learned cues as retrieval aids during
      the final test. In the present experiments, competitive practice or
      noncompetitive practice was followed by either final cued-recall tests or
      recognition tests. In cued-recall tests, RIF was observed in both competitive and
      noncompetitive conditions. However, in recognition tests, RIF was observed only
      in the competitive condition and was absent in the noncompetitive condition. The
      result underscores the contribution of strength-dependent competition to RIF.
      However, recognition tests seem to be a reliable way of distinguishing between
      RIF due to retrieval inhibition or strength-dependent competition. 

PMID- 24129443
TI  - Dr Leon Morgenstern: a reflection.

PMID- 24129442
TI  - Is naming faces different from naming objects? Semantic interference in a face-
      and object-naming task.
AB  - A current debate regarding face and object naming concerns whether they are
      equally vulnerable to semantic interference. Although some studies have shown
      similar patterns of interference, others have revealed different effects for
      faces and objects. In Experiment 1, we compared face naming to object naming when
      exemplars were presented in a semantically homogeneous context (grouped by their
      category) or in a semantically heterogeneous context (mixed) across four cycles.
      The data revealed significant slowing for both face and object naming in the
      homogeneous context. This semantic interference was explained as being due to
      lexical competition from the conceptual activation of category members. When
      focusing on the first cycle, a facilitation effect for objects but not for faces
      appeared. This result permits us to explain the previously observed discrepancies
      between face and object naming. Experiment 2 was identical to Experiment 1, with
      the exception that half of the stimuli were presented as face/object names for
      reading. Semantic interference was present for both face and object naming,
      suggesting that faces and objects behave similarly during naming. Interestingly,
      during reading, semantic interference was observed for face names but not for
      object names. This pattern is consistent with previous assumptions proposing the
      activation of a person identity during face name reading. 

PMID- 24129446
TI  - Racer's pillow: Salvatore Scarpitta.

PMID- 24129449
TI  - IOM report: Aging US population, rising costs, and complexity of cases add up to
      crisis in cancer care.

PMID- 24129447
TI  - FDA tightens indications for using long-acting and extended-release opioids to
      treat chronic pain.

PMID- 24129448
TI  - Women with breast cancer who opt for contralateral prophylactic mastectomy may
      overestimate future risk.

PMID- 24129440
TI  - EXAFS simulation refinement based on broken-symmetry DFT geometries for the
      Mn(IV)-Fe(III) center of class I RNR from Chlamydia trachomatis.
AB  - Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into
      deoxyribonucleotides necessary for DNA biosynthesis. Unlike the conventional
      class Ia RNRs which use a diiron cofactor in their subunit R2, the active site of
      the RNR-R2 from Chlamydia trachomatis (Ct) contains a Mn/Fe cofactor. The
      detailed structure of the Mn/Fe core has yet to be established. In this paper we
      evaluate six different structural models of the Ct RNR active site in the
      Mn(iv)/Fe(iii) state by using Mossbauer parameter calculations and simulations of
      Mn/Fe extended X-ray absorption fine structure (EXAFS) spectroscopy, and we
      identify a structure similar to a previously proposed DFT-optimized model that
      shows quantitative agreement with both EXAFS and Mossbauer spectroscopic data. 

PMID- 24129460
TI  - Should health care systems become insurers?

PMID- 24129450
TI  - NIH, FDA setting up research centers to generate evidence base to inform tobacco
      regulation.

PMID- 24129461
TI  - Data and safety monitoring boards: academic credit where credit is due?

PMID- 24129438
TI  - Assessing the residual CFTR gene expression in human nasal epithelium cells
      bearing CFTR splicing mutations causing cystic fibrosis.
AB  - The major purpose of the present study was to quantify correctly spliced CFTR
      transcripts in human nasal epithelial cells from cystic fibrosis (CF) patients
      carrying the splicing mutations c.580-1G>T (712-1G>T) and c.2657+5G>A (2789+5G>A)
      and to assess the applicability of this model in CFTR therapeutic approaches. We
      performed the relative quantification of CFTR mRNA by reverse transcription
      quantitative PCR (RT-qPCR) of these splicing mutations in four groups (wild type,
      CF-F508del controls, CF patients and CF carriers) of individuals. In addition, in
      vitro assays using minigene constructs were performed to evaluate the effect of a
      new CF complex allele c.[2657+5G>A; 2562T>G]. Ex vivo qPCR data show that the
      primary consequence of both mutations at the RNA level is the skipping of their
      neighboring exon (6 and 16, respectively). The CFTR minigenes results mimicked
      the ex vivo data, as exon 16 skipping is the main aberrant transcript, and the
      correctly spliced transcript level was observed in a similar proportion when the
      c.2657+5G>A mutation is present. In summary, we provide evidence that ex vivo
      quantitative transcripts analysis using RT/qPCR is a robust technology that could
      be useful for measuring the efficacy of therapeutic approaches that attempt to
      achieve an increase in CFTR gene expression. 

PMID- 24129462
TI  - A piece of my mind. The warmth.

PMID- 24129463
TI  - Quality of life after PCI vs CABG among patients with diabetes and multivessel
      coronary artery disease: a randomized clinical trial.
AB  - IMPORTANCE: The FREEDOM trial demonstrated that among patients with diabetes
      mellitus and multivessel coronary artery disease, coronary artery bypass graft
      (CABG) surgery resulted in lower rates of death and myocardial infarction but a
      higher risk of stroke when compared with percutaneous coronary intervention (PCI)
      using drug-eluting stents. Whether there are treatment differences in health
      status, as assessed from the patient's perspective, is unknown. OBJECTIVES: To
      compare the relative effects of CABG vs PCI using drug-eluting stents on health
      status among patients with diabetes mellitus and multivessel coronary artery
      disease. DESIGN, SETTING, AND PARTICIPANTS: Between 2005 and 2010, 1900 patients
      from 18 countries with diabetes mellitus and multivessel coronary artery disease
      were randomized to undergo either CABG surgery (n = 947) or PCI (n = 953) as an
      initial treatment strategy. Of these, a total of 1880 patients had baseline
      health status assessed (935 CABG, 945 PCI) and comprised the primary analytic
      sample. INTERVENTIONS: Initial revascularization with CABG surgery or PCI. MAIN
      OUTCOMES AND MEASURES: Health status was assessed using the angina frequency,
      physical limitations, and quality-of-life domains of the Seattle Angina
      Questionnaire at baseline, at 1, 6, and 12 months, and annually thereafter. For
      each scale, scores range from 0 to 100 with higher scores representing better
      health. The effect of CABG surgery vs PCI was evaluated using longitudinal mixed
      effect models. RESULTS: At baseline, mean (SD) scores for the angina frequency,
      physical limitations, and quality-of-life subscales of the Seattle Angina
      Questionnaire were 70.9 (25.1), 67.3 (24.4), and 47.8 (25.0) for the CABG group
      and 71.4 (24.7), 69.9 (23.2), and 49.2 (25.7) for the PCI group, respectively. At
      2-year follow-up, mean (SD) scores were 96.0 (11.9), 87.8 (18.7), and 82.2 (18.9)
      after CABG and 94.7 (14.3), 86.0 (19.3), and 80.4 (19.6) after PCI, with
      significantly greater benefit of CABG on each domain (mean treatment benefit, 1.3
      [95% CI, 0.3-2.2], 4.4 [95% CI, 2.7-6.1], and 2.2 [95% CI, 0.7-3.8] points,
      respectively; P < .01 for each comparison). Beyond 2 years, the 2
      revascularization strategies provided generally similar patient-reported
      outcomes. CONCLUSIONS AND RELEVANCE: For patients with diabetes and multivessel
      CAD, CABG surgery provided slightly better intermediate-term health status and
      quality of life than PCI using drug-eluting stents. The magnitude of benefit was
      small, without consistent differences beyond 2 years, in part due to the higher
      rate of repeat revascularization with PCI. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00086450.

PMID- 24129464
TI  - Metoclopramide in pregnancy and risk of major congenital malformations and fetal
      death.
AB  - IMPORTANCE: Metoclopramide, a drug frequently used for nausea and vomiting in
      pregnancy, is thought to be safe, but information on the risk of specific
      malformations and fetal death is lacking. OBJECTIVE: To investigate the safety of
      metoclopramide use in pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Register
      based cohort study in Denmark, 1997-2011. From a cohort of 1,222,503 pregnancies,
      metoclopramide-exposed and unexposed women were matched (1:4 ratio) on the basis
      of age, calendar year, and propensity scores. MAIN OUTCOMES AND MEASURES: Primary
      outcomes were major congenital malformations overall, 20 individual malformation
      categories (selected according to power criteria), spontaneous abortion, and
      stillbirth. In matched analyses, logistic regression was used to estimate
      prevalence odds ratios of malformations and Cox regression to estimate hazard
      ratios (HRs) of spontaneous abortion. RESULTS: Among 28,486 women exposed to
      metoclopramide in the first trimester, 721 had an infant with a major congenital
      malformation (25.3 [95% CI, 23.5-27.1] cases per 1000 births), compared with 3024
      among 113,698 unexposed women (26.6 [95% CI, 25.7-27.5] per 1000 births). There
      were no significant associations between metoclopramide use and malformations
      overall (prevalence odds ratio, 0.93 [95% CI, 0.86-1.02]) or any of the 20
      individual malformation categories, eg, neural tube defects, transposition of
      great vessels, ventricular septal defect, atrial septal defect, tetralogy of
      Fallot, coarctation of the aorta, cleft lip, cleft palate, anorectal
      atresia/stenosis, and limb reduction (upper limit of 95% CI below 2.0 for 17 of
      20 categories). Metoclopramide was not associated with increased risk of
      spontaneous abortion (757 cases [20.0 {95% CI, 18.5-21.4} per 1000] among 37,946
      metoclopramide-exposed women and 9414 cases [62.1 {95% CI, 60.9-63.3} per 1000]
      among 151,661 unexposed women; HR, 0.35 [95% CI, 0.33-0.38]) and stillbirth (142
      cases [3.5 {95% CI, 2.9-4.1} per 1000] among 40,306 metoclopramide-exposed women
      and 634 cases [3.9 {95% CI, 3.6-4.2} per 1000] among 161,098 unexposed women; HR,
      0.90 [95% CI, 0.74-1.08]). CONCLUSIONS AND RELEVANCE: Metoclopramide use in
      pregnancy was not associated with increased risk of major congenital
      malformations overall, any of the 20 individual malformation categories assessed,
      spontaneous abortion, or stillbirth. These safety data may help inform decision
      making when treatment with metoclopramide is considered in pregnancy.

PMID- 24129465
TI  - Management of asymptomatic internal carotid artery stenosis.
AB  - Optimal management of patients with asymptomatic carotid artery stenosis remains
      unclear. Although 2 high-quality randomized clinical trials demonstrated
      reductions in ispsilateral stroke rates in patients without symptoms after
      carotid endarterectomy, medical therapy of asymptomatic carotid artery stenosis
      has reduced rates of stroke to approximately 1% per year, raising questions about
      the generalizability of these previous trials to current medical practice.
      However, reductions in adverse events after revascularization can make
      revascularization more attractive. The emergence of percutaneous
      revascularization for carotid artery stenosis has raised further questions about
      optimal management of asymptomatic carotid artery stenosis. This Grand Rounds
      summarizes the factors to consider when counseling patients and making clinical
      decisions regarding medical therapy and revascularization for patients with
      asymptomatic carotid artery stenosis. This information should provide clinicians
      with the knowledge base to counsel patients about the risks and benefits of
      treatment options. 

PMID- 24129466
TI  - Antiretroviral therapy for prevention of HIV transmission in HIV-discordant
      couples.
AB  - CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant
      couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE
      Compared with serodiscordant couples without treatment, couples in which the
      infected partner is treated with antiretroviral therapy have a lower risk of HIV
      transmission. 

PMID- 24129467
TI  - Variation among primary care physicians in prostate-specific antigen screening of
      older men.

PMID- 24129468
TI  - Comparison of methods to diagnose sarcoidosis.

PMID- 24129469
TI  - Comparison of methods to diagnose sarcoidosis.

PMID- 24129470
TI  - Comparison of methods to diagnose sarcoidosis--reply.

PMID- 24129471
TI  - Drug discount program.

PMID- 24129472
TI  - Drug discount program.

PMID- 24129474
TI  - Drug discount program--reply.

PMID- 24129476
TI  - The water-supply of rural communities.

PMID- 24129477
TI  - JAMA patient page. Abdominal bloating.

PMID- 24129478
TI  - Dissemination of family-centered prevention for military and veteran families:
      adaptations and adoption within community and military systems of care.
AB  - In response to the needs of military families confronting the challenges of
      prolonged war, we developed Families OverComing Under Stress (FOCUS), a multi
      session intervention for families facing multiple deployments and combat stress
      injuries adapted from existing evidence-based family prevention interventions
      (Lester et al. in Mil Med 176(1): 19-25, 2011). In an implementation of this
      intervention contracted by the US Navy Bureau of Medicine and Surgery (BUMED),
      FOCUS teams were deployed to military bases in the United States and the Pacific
      Rim to deliver a suite of family-centered preventive services based on the FOCUS
      model (Beardslee et al. in Prev Sci 12(4): 339-348, 2011). Given the number of
      families affected by wartime service and the changing circumstances they faced in
      active duty and veteran settings, it rapidly became evident that adaptations of
      this approach for families in other contexts were needed. We identified the core
      elements of FOCUS that are essential across all adaptations: (1) Family
      Psychological Health Check-in; (2) family-specific psychoeducation; (3) family
      narrative timeline; and (4) family-level resilience skills (e.g., problem
      solving). In this report, we describe the iterative process of adapting the
      intervention for different groups of families: wounded, ill, and injured
      warriors, families with young children, couples, and parents. We also describe
      the process of adopting this intervention for use in different ecological
      contexts to serve National Guard, Reserve and veterans, and utilization of
      technology-enhanced platforms to reach geographically dispersed families. We
      highlight the lessons learned when faced with the need to rapidly deploy
      interventions, adapt them to the changing, growing needs of families under real
      world circumstances, and conduct rigorous evaluation procedures when long-term,
      randomized trial designs are not feasible to meet an emergent public health need.

PMID- 24129479
TI  - Journal policy on research funded by the tobacco industry.

PMID- 24129480
TI  - Risk of moderate to advanced kidney disease in patients with psoriasis:
      population based cohort study.
AB  - OBJECTIVE: To determine the risk of chronic kidney disease in patients with
      psoriasis. DESIGN: Population based cohort study and nested cross sectional
      study. SETTING: Electronic medical records database based in United Kingdom.
      PARTICIPANTS: Cohort study: patients with psoriasis aged 18-90 each matched to up
      to five patients without psoriasis based on age, practice, and time of visit.
      Nested study: patients with psoriasis aged 25-64 with confirmed data on psoriasis
      severity, each matched to up to 10 patients without psoriasis based on age and
      practice. MAIN OUTCOME MEASURES: Cohort study: incident moderate to advanced
      (stage 3 through 5) chronic kidney disease. Nested study: baseline prevalence of
      chronic kidney disease. RESULTS: 136,529 patients with mild psoriasis and 7354
      patients with severe psoriasis based on treatment patterns were matched to
      689,702 unaffected patients. The adjusted hazard ratios (95% confidence
      intervals) for incident chronic kidney disease were 1.05 (1.02 to 1.07), 0.99
      (0.97 to 1.02), and 1.93 (1.79 to 2.08) in the overall, mild, and severe
      psoriasis groups, respectively. Age was a significant effect modifier in the
      severe psoriasis group, with age specific adjusted hazard ratios (95% confidence
      intervals) of 3.82 (3.15 to 4.64) and 2.00 (1.86 to 2.17) for patients aged 30
      and 60, respectively. In the nested analysis of 8731 patients with psoriasis with
      measurements of affected body surface area matched to 87,310 patients without
      psoriasis, the adjusted odds ratios (95% confidence intervals) for chronic kidney
      disease were 0.89 (0.72 to 1.10), 1.36 (1.06 to 1.74), and 1.58 (1.07 to 2.34) in
      the mild, moderate, and severe psoriasis groups, respectively. CONCLUSIONS:
      Moderate to severe psoriasis is associated with an increased risk of chronic
      kidney disease independent of traditional risk factors.

PMID- 24129481
TI  - Integrative deficits in depression and in negative mood states as a result of
      fronto-parietal network dysfunctions.
AB  - Depression is a disorder characterized not only by persistent negative mood, lack
      of motivation and a "ruminative" style of thinking, but also by specific deficits
      in cognitive functioning. These deficits are especially pronounced when
      integration of information is required. Previous research on linear syllogisms
      points to a clear pattern of cognitive disturbances present in people suffering
      from depressive disorders, as well as in people with elevated negative mood. Such
      disturbances are characterized by deficits in the integration of piecemeal
      information into coherent mental representations. In this review, I present
      evidence which suggests that the dysfunction of specific brain areas plays a
      crucial role in creating reasoning and information integration problems among
      people with depression and with heightened negative mood. As the increasingly
      prevalent systems neuroscience approach is spreading into the study of mental
      disorders, it is important to understand how and which brain networks are
      involved in creating certain symptoms of depression. Two large brain networks are
      of particular interest when considering depression: the default mode network
      (DMN) and the fronto-parietal (executive) network (FNP). The DMN network shows
      abnormally high activity in the depressed population, whereas FNP circuit
      activity is diminished. Disturbances within the FNP network seem to be strongly
      associated with cognitive problems in depression, especially those concerning
      executive functions. The dysfunctions within the fronto-parietal network are most
      probably connected to ineffective transmission of information between prefrontal
      and parietal regions, and also to an imbalance between FNP and DMN circuits.
      Inefficiency of this crucial circuits functioning may be a more general mechanism
      leading to problems with flexible cognition and executive functions, and could be
      the cause of more typical symptoms of depression like persistent rumination. 

PMID- 24129482
TI  - Inhibition of natriuresis in median eminence polydipsia: effects after intake of
      diets with different osmolalities and after hypertonic NaCl administration.
AB  - Lesions in the hypothalamic median eminence (ME) induce polydipsia and polyuria
      in male rats. A first experiment was designed to examine the effect of salt
      consumption (standard 0.25 percent Na+ vs. low-salt 0.04 percent Na+ diet) on the
      fluid-electrolytic balance (plasma sodium, urinary sodium excretion, urine
      osmolality) and water intake of ME polydipsic animals. In the first 6 h post
      surgery, the natriuretic response was higher in ME-lesioned animals than in
      control groups. At 24 h post-surgery, however, less sodium was excreted by ME
      rats fed with a standard salt diet (ME/SS), despite showing no decrease in salt
      intake, and they evidenced an increase in plasma sodium concentration and water
      intake. Urine osmolality was significantly higher in control animals than in
      either ME-lesioned group. In experiment 2, hypertonic NaCl administration (2
      ml/2M) increased the polydipsic behavior of ME-lesioned but not control rats (day
      2). Animals deprived of food/salt showed a significant reduction (on day 2) in
      the initial (day 1) polydipsia, which increased on day 3 when the animals had
      access to a standard-salt diet. These results suggest that the reduced
      natriuretic response and the consequent sodium retention observed in ME animals
      may exacerbate the hydromineral imbalance of this polydipsic syndrome. 

PMID- 24129483
TI  - Cholinergic and nitrergic neuronal networks in the goldfish telencephalon.
AB  - The general organization of cholinergic and nitrergic elements in the central
      nervous system seems to be highly conserved among vertebrates, with the
      involvement of these neurotransmitter systems now well established in sensory,
      motor and cognitive processing. The goldfish is a widely used animal model in
      neuroanatomical, neurophysiological, and behavioral research. The purpose of this
      study was to examine pallial and subpallial cholinoceptive, cholinergic and
      nitrergic populations in the goldfish telencephalon by means of histochemical and
      immunohistochemical techniques in order to identify neurons containing
      acetylcholinesterase (AChE), choline acetyltransferase (ChAT), NADPH-diaphorase
      (NADPHd), and neuronal nitric oxide synthase (nNOS), and to relate their
      distribution to their putative functional significance. Regions containing AChE
      labeled neurons represented terminal fields of cholinergic inputs as well as a
      widespread distribution of AChE-related enzymes; these regions also usually
      contained NADPHd-labeled neurons and often contained small numbers of nNOS
      positive cells. However, the ventral subdivisions of the medial and lateral parts
      of the dorsal telencephalic area, and the ventral and lateral parts of the
      ventral telencephalic area, were devoid of nNOS-labeled cells. ChAT-positive
      neurons were found only in the lateral part of the ventral telencephalic area.
      ChAT- and nNOS-positive fibers exhibited a radial orientation, and were seen as
      thin axons with en-passant boutons. The distribution of these elements could help
      to elucidate the role of cholinergic and nitrergic neuronal networks in the
      goldfish telencephalon. 

PMID- 24129484
TI  - Bone marrow stromal cell transplantation enhances recovery of motor function
      after lacunar stroke in rats.
AB  - This study was aimed to clarify if the bone marrow stromal cells (BMSCs)
      significantly improve functional outcome after lacunar stroke when
      stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump
      inhibitor, was stereotactically injected into the right striatum of Wistar rats.
      One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7)
      or vehicle (n=8) were stereotactically transplanted into the left striatum. Using
      rotarod test, motor function was serially evaluated through the experiment. A 7.0
      T MR apparatus was employed to serially monitor the migration of BMSCs in the
      host brain. Histological analysis was performed at 7 weeks after ouabain
      injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded
      the reproducible, focal lesion in the right striatum, causing continuous motor
      dysfunction throughout the experiment. BMSC transplantation significantly
      enhanced the recovery of motor function after ouabain injection. MR imaging
      demonstrated that the BMSCs aggressively migrated towards the lesion through the
      corpus callosum. Histological analysis supported the findings on MRI. The BMSCs
      significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both
      sides. Some of them also expressed neuronal or astrocytic phenotypes in the
      neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly
      suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when
      stereotactically transplanted at clinically relevant timing. 

PMID- 24129485
TI  - Hippocampal interleukin-1beta in the juvenile and middle-aged rat: response to
      chronic forced swim or high-light open-field stress stimulation.
AB  - It is postulated that stress differentially affects interleukin-1beta (IL-1beta)
      during ontogenetic life. This study examined the influence of chronic exposure to
      forced swim (FS) stress or high-light open-field (HL-OF) stress on interleukin
      1beta (IL-1beta). The total level of IL-1beta protein was assessed by Western
      blot analysis of hippocampal extracts. Double immunofluorescence staining was
      used to reveal the percentage of IL-1beta/NeuN (NeuN - neuronal marker) cells in
      the CA1, CA3 and dentate gyrus (DG) hippocampal subfields. Juvenile (P28; P -
      postnatal day) and middle-aged (P360) rats were used in the experiment. The
      research showed no significant differences in IL-1beta protein levels between P28
      and P360 non-stress rats. However, a substantial increase in the percentage of IL
      1beta-ir neurons in the CA1, CA3 and DG in P360 rats was observed. Chronic FS had
      no significant influence on IL-1beta expression in the hippocampus or on the
      percentage of IL-1beta-ir neurons in CA1, CA3 and DG hippocampal subfields in
      either age group. During HL-OF, the IL-1beta level was significantly increased in
      the hippocampus of P28 and P360 rats, whereas a marked increase in the percentage
      of IL-1beta-ir neurons in the CA1, CA3 and DG hippocampal areas occurred only in
      P360 animals. These results indicate that chronic HL-OF stimulation was the
      factor inducing changes in the IL-1beta protein levels in P28 and P360 rats and
      in the percentage of IL-1beta/NeuN-ir cells in the hippocampus of P360 animals. 

PMID- 24129486
TI  - Ganglioside GM1 reduces white matter damage in neonatal rats.
AB  - This study investigated the neuronal protective effect of
      monosialotetrahexosylganglioside (GM1) on the hypoxia-ischemia white matter
      damage (WMD) in neonatal rats. Brain hypoxia-ischemia was induced by bilateral
      carotid artery occlusion in 4-day-old neonatal rats. Bilateral carotid artery
      occlusion (BCAO) was performed in rats in WMD and GM1 groups, while in sham
      group; the rat bilateral carotid arteries were merely exposed without occlusion.
      Immunohistochemical staining was used to determine the expression of myelin basic
      protein (MBP), glial fibrillary acidic protein (GFAP), and beta-amyloid precursor
      protein (beta-APP). In addition, suspension test, slope test, and open-field test
      were carried out on day 26 after BCAO to determine the neurobehavioral function.
      The percentage of MBP-positive cells was decreased while beta-APP-and
      GFAPpositive cells were increased in WMD group. After treated with GM1, the
      percentage of MBP-positive cells increased significantly than WMD rats at post
      operation 72 h and day 7. GFAP-positive cells and beta-APP-positive cells
      decreased significantly in WMD group at post-operation 72 h, day 7 and 26. The
      suspension test, slope test, and open-field test showed that neurobehavioral
      function was improved in ganglioside GM1 group compared with WMD group. Taken
      together, our findings suggested that ganglioside GM1 treatment reduces hypoxia
      ischemia induced impairment of the neurobehavioral function in WMD in neonatal
      rats. 

PMID- 24129487
TI  - Early postweaning social isolation but not environmental enrichment modifies
      vermal Purkinje cell dendritic outgrowth in rats.
AB  - In the present study, we analyzed the effects of enriched, social and isolated
      experiences on vermal Purkinje cell of the rat, together with anxiety-like
      behavior in the elevated-plus maze. Sprague-Dawley male rats were randomly
      submitted to either enriched, social, or isolated environments during the early
      postweaning period (postnatal days 22-32) and were then behaviorally evaluated in
      the elevated-plus maze and euthanized for histological analysis. Vermal Purkinje
      cells (sub-lobules VIa and VIb) were sampled, drawn under camera lucida and
      morphometrically assessed using the Sholl's concentric ring method. Data obtained
      indicate that environmental enrichment did not significantly modify the Purkinje
      cell dendritic branching. On the contrary, Purkinje cell of animals reared in
      social isolation exhibited a significant reduction in dendritic arborization,
      which was closely associated with anxiety-like behaviors. The data obtained
      indicate that, although environmental stimulation in normal animals does not
      produce significant changes in vermal Purkinje cell dendritic arborization, these
      cells are vulnerable to early stressful experiences, which is in close
      association with anxiety-like behaviors. 

PMID- 24129488
TI  - Long-term effects of the maternal deprivation on the volume and number of neurons
      in the rat neocortex and hippocampus.
AB  - Maternal deprivation (MD) leads to a variety of behavioral changes in rats which
      closely resemble the symptoms of schizophrenia in humans. With the aim to
      investigate the morphological changes which underlie the behavioral insults in
      this experimental paradigm we exposed 9-day-old Wistar rats to a 24 h MD. At the
      period of young adulthood rats were sacrificed for morphometric analysis and
      their brains were compared to the control group. Rats exposed to MD had a
      decrease in hippocampal volume (71 percent of the control value) as well as a
      decrease in the size of pyramidal (62 percent of the control) and granular (60
      percent of the control) cell layers. Also, there was a decrease in the thickness
      of the prefrontal, retrosplenial and motor cortex compared to the control group.
      Analysis of the density of NeuN-immunolabeled neurons revealed a reduction in
      retrosplenial and prefrontal cortex (70 percent and 81 percent of the control,
      respectively), while there was no difference in the motor cortex. Western blot
      analysis confirmed a decrease in NeuN expression in the MD group compared to the
      control rat brain homogenates. The results of this study show that early stress
      in life has a long-term effect on the morphology of cognitive brain regions, most
      probably due to the loss of neurons during postnatal development and further
      contributes to our understanding of the effects of maternal separation on brain
      development. 

PMID- 24129489
TI  - Distinct neural signatures of cognitive subtypes of dyslexia: effects of
      lexicality during phonological processing.
AB  - The present study investigates the neurobiological basis of two subtypes of
      dyslexia with either a double deficit (concerning phonological awareness and
      rapid naming) or a single rapid naming deficit. We compared such groups of German
      dyslexic primary school children to each other and with good reading children in
      a phoneme deletion task performed during fMRI scanning. Children heard German
      words or pseudowords and repeated the remainder of the stimulus while deleting
      the initial phoneme (e.g. tear - _ear). In four conditions, the input stimulus
      (word or pseudoword) could either become another word or pseudoword as output.
      The word-word condition stuck out against all other conditions involving
      pseudowords: Dyslexics with a double deficit showed a strong response in left
      areas 44 and 45 in Boca's region, whereas dyslexics with rapid naming
      difficulties revealed a contralateral effect in right areas 44 and 45. These
      findings, which were obtained without presenting written or pictorial stimuli,
      reveal that a double deficit in dyslexia is not the sum of single deficits, but
      rather involves the interaction of lexical and phonological processing, making
      strong demands on the left inferior frontal cortex. In general, the results
      stress the importance of considering subtypes of dyslexia differentially in order
      to obtain better insights in the neurocognitive mechanisms of impaired and
      successful reading. 

PMID- 24129490
TI  - Perceptual mislocalization of a single set of the Muller-Lyer wings.
AB  - In the present communication, a possible role of perceptual displacements of
      stimulus elements in the occurrence of visual illusions of extent has been
      considered. In psychophysical experiments with a single set of Muller-Lyer wings,
      subjects were asked to place an imaginary reference rectangle into a position
      that made the apex of the wings appear to be at the rectangle center. Three
      different stimulus parameters (the length, internal angle, or tilt angle of the
      wings) were used as independent variables in different series of experiments. It
      was demonstrated that the magnitude of perceptual displacements of stimulus
      terminator is commensurate with that of illusions of extent obtained in our
      previous studies of full versions of illusory figures. Good correspondence
      between the experimental data and the predictions of our computational model of
      automatic centroid extraction strongly supported the suggestion that the effects
      of centroid extraction are powerful enough to be considered as one of the main
      causes of illusions of extent of the Muller-Lyer type. 

PMID- 24129491
TI  - Lesions of the lateral entorhinal cortex disrupt non-spatial latent learning but
      spare spatial latent learning in the rat (Rattus norvegicus).
AB  - The current study examined the function of the lateral entorhinal cortex (LEC) in
      a non-spatial latent learning task and a spatial latent learning task. Latent
      learning is the acquisition of neutral information that does not immediately
      influence behavior, but can be recalled and utilized when it becomes relevant to
      the animal. Based on previous research, it was predicted that the LEC would be
      necessary for latent learning of non-spatial information, but would not be
      necessary for latent learning of spatial information. Forty-two male Sprague
      Dawley rats (Rattus norvegicus) were either given pretraining neurotoxic lesions
      restricted to the LEC or were given sham (SH) lesions. The rats were then trained
      and tested on two latent learning tasks: the Latent Cue Preference (LCP) task
      which assesses single-cue (non-spatial) latent learning and a spatial latent
      learning task utilizing a Barnes maze. Results showed that rats with LEC lesions
      were impaired on the nonspatial LCP task compared to SH rats, but showed no
      impairment on the spatial latent learning task. Therefore, the LEC appears to be
      selectively involved in processing non-spatial latent learning and does not
      process, or is at least not necessary for, spatial latent learning. These
      findings indicate a specific role of the LEC in information processing and
      provide new information about the function of the entorhinal cortex. 

PMID- 24129492
TI  - Visualization of the joining of ribosomal subunits reveals the presence of 80S
      ribosomes in the nucleus.
AB  - In eukaryotes the 40S and 60S ribosomal subunits are assembled in the nucleolus,
      but there appear to be mechanisms preventing mRNA binding, 80S formation, and
      initiation of translation in the nucleus. To visualize association between
      ribosomal subunits, we tagged pairs of Drosophila ribosomal proteins (RPs)
      located in different subunits with mutually complementing halves of fluorescent
      proteins. Pairs of tagged RPs expected to interact, or be adjacent in the 80S
      structure, showed strong fluorescence, while pairs that were not in close
      proximity did not. Moreover, the complementation signal is found in ribosomal
      fractions and it was enhanced by translation elongation inhibitors and reduced by
      initiation inhibitors. Our technique achieved 80S visualization both in cultured
      cells and in fly tissues in vivo. Notably, while the main 80S signal was in the
      cytoplasm, clear signals were also seen in the nucleolus and at other nuclear
      sites. Furthermore, we detected rapid puromycin incorporation in the nucleolus
      and at transcription sites, providing an independent indication of functional 80S
      in the nucleolus and 80S association with nascent transcripts. 

PMID- 24129493
TI  - Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as
      important factors in anoikis resistance.
AB  - MicroRNAs (miRNAs) have been widely studied in order to elucidate their
      biological functions. MicroRNA microarrays or miRNA overexpression libraries
      generated by synthesis and cloning of individual miRNAs have been used to study
      their different roles. In this work, we have developed a novel methodology to
      express mature miRNAs and other small RNAs from a double convergent RNA
      polymerase III promoter. We show that the generated miRNAs function similarly to
      those processed from primary transcripts or pri-miRNAs. This system allowed us to
      produce a lentiviral library expressing the whole population of small RNAs
      present in a metastatic cell line. A functional screening using this library led
      to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of
      cell death induced by loss of attachment (anoikis). Importantly, we demonstrated
      that the acquisition of anoikis resistance via these miRNAs is achieved through
      down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs
      resulted in a decrease of other types of caspase 3-dependent cell death and
      enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting
      a putative role as oncomirs. In summary, this novel methodology provides a
      powerful and effective way for identifying novel small RNAs involved in a
      particular biological process. 

PMID- 24129495
TI  - Gold plating of silver nanoparticles for superior stability and preserved
      plasmonic and sensing properties.
AB  - Gold-plated silver nanoparticles (Au@AgNPs, shell@core) with high stability in
      various environments detrimental to AgNPs have been produced with preserved
      plasmonic and sensing properties. 

PMID- 24129494
TI  - Identification of the binding site of Rlp7 on assembling 60S ribosomal subunits
      in Saccharomyces cerevisiae.
AB  - Eukaryotic ribosome assembly requires over 200 assembly factors that facilitate
      rRNA folding, ribosomal protein binding, and pre-rRNA processing. One such factor
      is Rlp7, an essential RNA binding protein required for consecutive pre-rRNA
      processing steps for assembly of yeast 60S ribosomal subunits: exonucleolytic
      processing of 27SA3 pre-rRNA to generate the 5' end of 5.8S rRNA and
      endonucleolytic cleavage of the 27SB pre-rRNA to initiate removal of internal
      transcribed spacer 2 (ITS2). To better understand the functions of Rlp7 in 27S
      pre-rRNA processing steps, we identified where it crosslinks to pre-rRNA. We
      found that Rlp7 binds at the junction of ITS2 and the ITS2-proximal stem, between
      the 3' end of 5.8S rRNA and the 5' end of 25S rRNA. Consistent with Rlp7 binding
      to this neighborhood during assembly, two-hybrid and affinity copurification
      assays showed that Rlp7 interacts with other assembly factors that bind to or
      near ITS2 and the proximal stem. We used in vivo RNA structure probing to
      demonstrate that the proximal stem forms prior to Rlp7 binding and that Rlp7
      binding induces RNA conformational changes in ITS2 that may chaperone rRNA
      folding and regulate 27S pre-rRNA processing. Our findings contradict the
      hypothesis that Rlp7 functions as a placeholder for ribosomal protein L7, from
      which Rlp7 is thought to have evolved in yeast. The binding site of Rlp7 is
      within eukaryotic-specific RNA elements, which are not found in bacteria. Thus,
      we propose that Rlp7 coevolved with these RNA elements to facilitate eukaryotic
      specific functions in ribosome assembly and pre-rRNA processing. 

PMID- 24129496
TI  - Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer
      risk: evidence from the meta-analysis.
AB  - Folate is essential for DNA synthesis and methylation and implicated in the
      process of carcinogenesis. Several studies inconclusively suggested increased
      folate intake may reduce ovarian cancer risk. Studies concerning the association
      between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), an
      important enzyme in folate metabolism, and ovarian cancer risk also resulted in
      no agreement. The meta-analysis was conducted based on current studies to assess
      the association between folate intake, the MTHFR C667T polymorphism and ovarian
      cancer risk. 1,158 cases out of 217,309 participants from four cohort studies,
      4,519 cases and 6,031 controls from four case-control studies about folate intake
      along with 5,617 cases and 9,808 controls from 10 publications concerning the
      polymorphism were pooled, respectively. We detected no significant association
      between total folate (RR = 1.04, 95 % confidence interval (CI) = 0.87-1.23) or
      dietary folate (RR = 0.88, 95 % CI = 0.75-1.05) intake and ovarian cancer risk,
      and also no significant relationship was found between MTHFR C677T polymorphism
      and ovarian cancer risk (TT vs. CC: odds ratio (OR) = 1.15, 95 % CI = 0.90-1.46;
      CT vs. CC: OR = 1.04, 95 % CI = 0.94-1.16). Our analysis indicated neither folate
      intake nor MTHFR C677T polymorphism is related to altered susceptibility of
      ovarian cancer. 

PMID- 24129497
TI  - Research accomplishments that are too good to be true.

PMID- 24129498
TI  - Regioselective halogenation of 2-substituted-1,2,3-triazoles via sp2 C-H
      activation.
AB  - A highly regioselective halogenation of 2-substituted-1,2,3-triazoles was
      developed via sp(2) C-H activation. This method is compatible with halogen atoms,
      as well as electron-donating and electron-withdrawing groups. Meanwhile, the
      strategy is also efficient for the synthesis of a key intermediate of Suvorexant.

PMID- 24129499
TI  - Molecular pathology of acute kidney injury in a choline-deficient model and fish
      oil protective effect.
AB  - PURPOSE: The aim of this work was to investigate the potential protective effects
      of fish oil on the basis of kidney transcriptomic data on a nutritional
      experimental model. METHODS: Male weanling Wistar rats were divided into four
      groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with
      vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were
      killed after receiving the diets for 6 days. Total RNA was purified from the
      right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array.
      Differentially expressed genes were analyzed. RESULTS: All CSVO, CSMO and CDMO
      rats showed no renal alterations, while all CDVO rats showed renal cortical
      necrosis. A thorough analysis of the differential expression between groups CSMO
      and CDMO was carried out. There were no differential genes for p < 0.01. The
      analysis of the differential expression between groups CSVO and CSMO revealed 32
      genes, 11 were over-expressed and 21 were under-expressed in CSMO rats.
      CONCLUSIONS: This work was part of a large set of experiments and was used in a
      hypothesis-generating manner. The comprehensive analysis of genetic expression
      allowed confirming that menhaden oil has a protective effect on this nutritional
      experimental model and identifying 32 genes that could be responsible for that
      protection, including Gstp1. These results reveal that gene changes could play a
      role in renal injury.

PMID- 24129500
TI  - Adiponectin receptor 1 enhances fatty acid metabolism and cell survival in
      palmitate-treated HepG2 cells through the PI3 K/AKT pathway.
AB  - PURPOSES: Hepatic lipid overloading induces lipotoxicity which can cause
      hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is
      associated with nonalcoholic fatty liver disease. Adiponectin receptors play
      important roles in regulating lipid metabolism. In this study, we used a
      lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2
      cells to define the role of adiponectin and its receptor 1 in the development of
      fatty liver syndrome. METHODS AND RESULTS: Exposure of human hepatocytes, HepG2
      cells, to palmitate (0.2 or 0.4 mM) for 16 h resulted in elevated apoptosis,
      whereas AdipoR1 decreased the palmitate-induced apoptosis. Transgene AdipoR1
      increased the expression of FATP2, acyl-coA oxidase, and carnitine
      palmitoyltransferase I in palmitate-treated HepG2 cells. The transcript level of
      acetyl-CoA carboxylase and fatty acid synthase was upregulated by palmitate
      treatment, while AdipoR1 reversed the effect induced by palmitate. AdipoR1
      increased the gene expression of cytochrome C oxidase, peroxisome proliferator
      activated receptor alpha, and decreased the gene expression of PGC1alpha and
      AMPKalpha in HepG2 cells under palmitate treatment. Palmitate suppressed ATP
      production, while transgene AdipoR1 reversed the decreased ATP production by
      palmitate. Transgene AdipoR1 enhanced AKT phosphorylation in HepG2 cells both
      with and without palmitate treatment. When PI3 kinase inhibitor was applied, the
      protective effect of AdipoR1 was absent, such that palmitate again decreased ATP
      production while also reducing cell viability. CONCLUSION: AdipoR1 enhances fatty
      acid metabolism and cell viability in palmitate-treated HepG2 cells partially by
      activating AKT signaling. Therefore, AdipoR1 has therapeutic potential in the
      treatment of nonalcoholic fatty liver disease.

PMID- 24129501
TI  - Clinical consequences of using PNA-FISH in Staphylococcal bacteraemia.
AB  - To optimize patient treatment and rational use of antimicrobials, it is important
      to provide fast information on findings in blood-cultures (BCs). The purpose of
      this study was to evaluate the impact of using peptide nucleic acid fluorescence
      in situ hybridization (PNA-FISH) on positive BCs containing Gram-positive cocci
      in clusters to differentiate between Staphylococcus aureus (SA) and coagulase
      negative staphylococci (CoNS) on the prescribed antimicrobial therapy and on the
      number of contacts between microbiologist and clinician. All cases of positive
      BCs in our laboratory with SA or CoNS in the year 2011 were identified and the
      charts were reviewed retrospectively. The group of patients with BCs tested with
      PNA-FISH was compared to the group of patients with untested BCs. A total of 200
      patients with SA and 725 patients with CoNS were included. The mean number of
      contacts was 0.82 when PNA-FISH showed CoNS and 1.39 when PNA-FISH was not done
      (p < 0.0001). More patients were recommended appropriate antimicrobial therapy
      for SA bacteraemia in the PNA-FISH group (98.0%) than in the non-PNA-FISH group
      (89.4 %) (p = 0.025). The percentage treated with dicloxacillin was 29.6 in the
      PNA-FISH group, and 8.2 in the non-PNA-FISH group (p = 0.0003). The use of PNA
      FISH on BCs in this study was associated with more appropriate and narrow
      spectrum antimicrobial therapy for patients with SA in an area with low
      prevalence of methicillin-resistant SA, and a lower number of contacts between
      clinical microbiologist and clinician about BCs with CoNS as contaminants.

PMID- 24129503
TI  - Scaling space with the mirror illusion: the influence of body plasticity on
      perceived affordances.
AB  - How do body representations influence decisions about action? We developed a
      novel paradigm using the mirror illusion (Holmes, Crozier, & Spence, in
      Cognitive, Affective, & Behavioral Neuroscience, 4, 193-200, 2004) to examine two
      ways of evoking body plasticity-extension of body capabilities and visual capture
      and its influence on perceived affordances. In two experiments, we manipulated
      the action capabilities of a seen left hand by lengthening the arm with a rod
      (Exp. 1) or enlarging the hand with a glove (Exp. 2). The right hand was
      unaltered physically and was occluded by placement in a mirror box. We induced
      visual capture through synchronous finger movements of both hands. Right-hand
      estimates of reaching and of fitting through apertures increased relative to
      actual capabilities during visual capture, supporting the claim that visual
      capture can induce the incorporation of an apparent body extension into action
      decisions. The results suggest that both perceptual and cognitive influences on
      bodily awareness underlie perceived affordances.

PMID- 24129504
TI  - Technical clarification to Silbert and Thomas (2013): "decisional separability,
      model identification, and statistical inference in the general recognition theory
      framework".
AB  - We offer a minor technical correction to the published proof of part (ii) of the
      main theorem in Silbert and Thomas (Psychonomic Bulletin & Review, 20, 1-20,
      2013) that somewhat limits the scope of the equivalence observed in that work.
      Specifically, in order for a mean shift integrality with decisional separability
      to be mimicked by a perceptually separable but nondecisionally separable
      configuration, one needs to assume stimulus invariance. This holds when all of
      the covariance matrices in the stimulus configuration are equal to each other. We
      note that part (i) of the theorem is unaffected by this modification; an
      empirical finding of perceptual separability and the failure of decisional
      separability can be mimicked by a perceptually nonseparable, decisionally
      separable configuration without restricting the covariance matrices to be equal.
      We also note that stimulus invariance is often assumed in simple designs (e.g.,
      Macmillan & Ornstein in Journal of the Acoustical Society of America, 97, 1261
      1285, 1998), due to the implausibility of different perceptual correlations being
      present within stimuli perched very closely in perceptual space.

PMID- 24129505
TI  - Synthesis, characterization, and reversible hydrogen sorption study of sodium
      doped fullerene.
AB  - Herein is presented a novel, straightforward route to the synthesis of an alkali
      metal-doped fullerene as well as a detailed account of its reversible and
      enhanced hydrogen sorption properties in comparison to pure C60. This work
      demonstrates that a reaction of sodium hydride with fullerene (C60) results in
      the formation of a sodium-doped fullerene capable of reversible hydrogen sorption
      via a chemisorption mechanism. This material not only demonstrated reversible
      hydrogen storage over several cycles, it also showed the ability to reabsorb over
      three times the amount of hydrogen (relative to the hydrogen content of NaH)
      under optimized conditions. The sodium-doped fullerene was hydrogenated on a
      pressure composition temperature (PCT) instrument at 275  degrees C while under
      100 bar of hydrogen pressure. The hydrogen desorption behavior of this sodium
      doped fullerene hydride was observed over a temperature range up to 375  degrees
      C on the PCT and up to 550  degrees C on the thermogravimetric analysis (TGA).
      Powder x-ray diffraction verifies the identity of this material as being Na6C60.
      Characterization of this material by thermal decomposition analysis (e.g. PCT and
      TGA methods), as well as FT-IR and mass spectrometry, indicates that the hydrogen
      sorption activity of this material is due to the reversible formation of a
      hydrogenated fullerene (fullerane). However, the reversible formation of
      fullerane was found to be greatly enhanced by the presence of sodium. It was also
      demonstrated that the addition of a catalytic amount of titanium (via TiO2 or
      Ti(OBu)4) further enhances the hydrogen sorption process of the sodium-doped
      fullerene material.

PMID- 24129508
TI  - Bacterial physiology: bacterial argonaute sets sail.

PMID- 24129506
TI  - The genome of Mesobuthus martensii reveals a unique adaptation model of
      arthropods.
AB  - Representing a basal branch of arachnids, scorpions are known as 'living fossils'
      that maintain an ancient anatomy and are adapted to have survived extreme climate
      changes. Here we report the genome sequence of Mesobuthus martensii, containing
      32,016 protein-coding genes, the most among sequenced arthropods. Although M.
      martensii appears to evolve conservatively, it has a greater gene family turnover
      than the insects that have undergone diverse morphological and physiological
      changes, suggesting the decoupling of the molecular and morphological evolution
      in scorpions. Underlying the long-term adaptation of scorpions is the expansion
      of the gene families enriched in basic metabolic pathways, signalling pathways,
      neurotoxins and cytochrome P450, and the different dynamics of expansion between
      the shared and the scorpion lineage-specific gene families. Genomic and
      transcriptomic analyses further illustrate the important genetic features
      associated with prey, nocturnal behaviour, feeding and detoxification. The M.
      martensii genome reveals a unique adaptation model of arthropods, offering new
      insights into the genetic bases of the living fossils. 

PMID- 24129509
TI  - Cereal killers.

PMID- 24129510
TI  - RNA silencing suppression by plant pathogens: defence, counter-defence and
      counter-counter-defence.
AB  - RNA silencing is a central regulator of gene expression in most eukaryotes and
      acts both at the transcriptional level through DNA methylation and at the post
      transcriptional level through direct mRNA interference mediated by small RNAs. In
      plants and invertebrates, the same pathways also function directly in host
      defence against viruses by targeting viral RNA for degradation. Successful
      viruses have consequently evolved diverse mechanisms to avoid silencing, most
      notably through the expression of viral suppressors of RNA silencing. RNA
      silencing suppressors have also been recently identified in plant pathogenic
      bacteria and oomycetes, suggesting that disruption of host silencing is a general
      virulence strategy across several kingdoms of plant pathogens. There is also
      increasing evidence that plants have evolved specific defences against RNA
      silencing suppression by pathogens, providing yet another illustration of the
      never-ending molecular arms race between plant pathogens and their hosts. 

PMID- 24129512
TI  - RNA connectivity requirements between conserved elements in the core of the yeast
      telomerase RNP.
AB  - Telomerase is a specialized chromosome end-replicating enzyme required for genome
      duplication in many eukaryotes. An RNA and reverse transcriptase protein subunit
      comprise its enzymatic core. Telomerase is evolving rapidly, particularly its RNA
      component. Nevertheless, nearly all telomerase RNAs, including those of H.
      sapiens and S. cerevisiae, share four conserved structural elements: a core
      enclosing helix (CEH), template-boundary element, template, and pseudoknot, in
      this order along the RNA. It is not clear how these elements coordinate
      telomerase activity. We find that although rearranging the order of the four
      conserved elements in the yeast telomerase RNA subunit, TLC1, disrupts activity,
      the RNA ends can be moved between the template and pseudoknot in vitro and in
      vivo. However, the ends disrupt activity when inserted between the other
      structured elements, defining an Area of Required Connectivity (ARC). Within the
      ARC, we find that only the junction nucleotides between the pseudoknot and CEH
      are essential. Integrating all of our findings provides a basic map of functional
      connections in the core of the yeast telomerase RNP and a framework to understand
      conserved element coordination in telomerase mechanism. 

PMID- 24129511
TI  - Filamentous plant pathogen effectors in action.
AB  - Live-cell imaging assisted by fluorescent markers has been fundamental to
      understanding the focused secretory 'warfare' that occurs between plants and
      biotrophic pathogens that feed on living plant cells. Pathogens succeed through
      the spatiotemporal deployment of a remarkably diverse range of effector proteins
      to control plant defences and cellular processes. Some effectors can be secreted
      by appressoria even before host penetration, many enter living plant cells where
      they target diverse subcellular compartments and others move into neighbouring
      cells to prepare them before invasion. This Review summarizes the latest advances
      in our understanding of the cell biology of biotrophic interactions between
      plants and their eukaryotic filamentous pathogens based on in planta analyses of
      effectors. 

PMID- 24129514
TI  - A keystroke away.

PMID- 24129513
TI  - Endonuclease G mediates alpha-synuclein cytotoxicity during Parkinson's disease.
AB  - Malfunctioning of the protein alpha-synuclein is critically involved in the
      demise of dopaminergic neurons relevant to Parkinson's disease. Nonetheless, the
      precise mechanisms explaining this pathogenic neuronal cell death remain elusive.
      Endonuclease G (EndoG) is a mitochondrially localized nuclease that triggers DNA
      degradation and cell death upon translocation from mitochondria to the nucleus.
      Here, we show that EndoG displays cytotoxic nuclear localization in dopaminergic
      neurons of human Parkinson-diseased patients, while EndoG depletion largely
      reduces alpha-synuclein-induced cell death in human neuroblastoma cells.
      Xenogenic expression of human alpha-synuclein in yeast cells triggers
      mitochondria-nuclear translocation of EndoG and EndoG-mediated DNA degradation
      through a mechanism that requires a functional kynurenine pathway and the
      permeability transition pore. In nematodes and flies, EndoG is essential for the
      alpha-synuclein-driven degeneration of dopaminergic neurons. Moreover, the
      locomotion and survival of alpha-synuclein-expressing flies is compromised, but
      reinstalled by parallel depletion of EndoG. In sum, we unravel a phylogenetically
      conserved pathway that involves EndoG as a critical downstream executor of alpha
      synuclein cytotoxicity. 

PMID- 24129515
TI  - Therapy without consent.

PMID- 24129516
TI  - [New religiosity as a challenge].

PMID- 24129517
TI  - [Where is the patient's voice?].

PMID- 24129519
TI  - [Information about mammography screening].

PMID- 24129520
TI  - [Mammography screening--time to move focus].

PMID- 24129521
TI  - [P-H. Zahl replies].

PMID- 24129522
TI  - [Increasing internationalization and motivation].

PMID- 24129523
TI  - [Do we measure what we should be measuring?].

PMID- 24129524
TI  - [Is introducing grades the way to go?].

PMID- 24129525
TI  - [P. Gjersvik replies].

PMID- 24129528
TI  - [Milieu Therapy in sleep disorders in children with chronic illnesses].

PMID- 24129529
TI  - Guidelines for mass casualty triage have been established.

PMID- 24129530
TI  - [Exercise after heart transplantation--old principles needs reevaluation].

PMID- 24129531
TI  - [Blocking of generic drugs must be fought].

PMID- 24129532
TI  - [Wilderness medical expertise is also needed in Norway].

PMID- 24129535
TI  - Electroconvulsive therapy without consent.
AB  - BACKGROUND: In principle, electroconvulsive therapy (ECT) can only be
      administered to patients who consent to the treatment. If the patient does not
      consent, the treatment can be given in exceptional cases, in situations where a
      plea of necessity can be made. The purpose of this study was to investigate
      whether the issue of consent was documented in the patient records at Dikemark
      Hospital in the period 1960-95, and to study the outcomes for patients who were
      given ECT treatment without having consented. MATERIAL AND METHOD: The article is
      based on a review of the ECT protocols and the records of patients who were given
      this treatment during the period 1960-95 in three psychiatric wards at Dikemark
      Hospital. We registered whether the issue of consent had been documented, and if
      so, whether consent had been provided or not. The material encompasses 241 ECT
      series administered to 141 patients. RESULTS: The issue of consent had been
      documented for 107 of a total of the 241 series. Seven patients were given the
      therapy against their wishes. The median age of these seven was 68 years (range
      56-82 years). All of them had been diagnosed with depressive psychosis and were
      given electroconvulsive therapy on a vital indication under a plea of necessity.
      Insufficient intake of nourishment was described as the main reason for the vital
      indication in all the seven patients. According to their records, they showed
      signs of improvement on the day after the first treatment. Their lifespan after
      the treatment varied from three to 19 years. INTERPRETATION: On the basis of the
      records in which it was documented that the patient had not provided consent,
      electroconvulsive therapy was administered exclusively as a life-saving
      intervention.

PMID- 24129536
TI  - Use of antibiotics in nursing homes--surveillance with different methods.
AB  - BACKGROUND: Residents in nursing homes have a heightened risk of developing
      infections that should be treated with antibiotics. Inappropriate use of
      antibiotics may generate drug-related problems and increase resistance. In this
      study, we describe the use of antibiotics in nursing homes on the basis of
      prevalence surveys and drug sales statistics. MATERIAL AND METHODS: Five nursing
      homes in Oslo participated in two one-day surveys in 2009. All use of systemic
      antibiotics was registered. The data collection was undertaken according to a
      protocol developed by the European Surveillance of Antimicrobial Consumption
      (ESAC) Network and was part of a European study. The nursing homes' drug sales
      statistics for systemic antibiotics during 2009, distributed by the number of bed
      days for each nursing home, were estimated. Information on indications for each
      antibiotic from the prevalence surveys was collated with sales data to achieve an
      estimate of how the purchased antibiotics were used. RESULTS: The prevalence
      surveys showed that more than 8% of the residents received antibiotics.
      Prophylactic treatment accounted for 33% of the prescriptions. A prevalence of
      antibiotic use of 10% was estimated from the drug sales statistics. Urinary tract
      infection was the most frequently registered indication. Pivmecillinam and
      methenamine were most frequently prescribed and most frequently purchased. Most
      courses of treatment were prescribed in accordance with the national guidelines
      for antibiotic use. INTERPRETATION: The results from the drug sales statistics
      concurred well with the prevalence surveys, and the methods can thus be relevant
      for purposes of monitoring the use of antibiotics.

PMID- 24129537
TI  - [Neuromyelitis optica].
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a rare autoimmune inflammatory disease
      of the central nervous system that is characterized mainly by recurrent optic
      neuritis and longitudinally extensive transverse myelitis. The aim of this
      article is to present current knowledge on the clinical features, diagnosis,
      pathogenesis and treatment of the condition. METHOD: The article is based on a
      discretionary selection of English-language original articles, meta-analyses and
      review articles found in PubMed, and on the authors' own experience with the
      patient group. RESULTS: Neuromyelitis optica was previously assumed to be a
      variant of multiple sclerosis (MS), but the discovery of aquaporin-4 antibodies
      in patients with neuromyelitis optica has led to this view being revised. The
      cause of the condition is still unknown, but it has been shown that the
      antibodies bind selectively to a water channel expressed mainly on astrocytes at
      the blood-brain-barrier, which has an important role in the regulation of brain
      volume and ion homeostasis. Clinically, the condition presents as optic neuritis
      and/or transverse myelitis. A diagnosis is made on the basis of case history,
      clinical examination, MRI of the brain and spinal cord, analysis of cerebrospinal
      fluid, visual evoked potentials and a blood test with analysis of aquaporin-4
      antibodies. Once a diagnosis has been made, rapid treatment is important. In the
      acute phase, intravenous methylprednisolone is recommended. There are several
      options for preventative treatment, but the primary recommendations are oral
      prednisolone and azathioprine or intravenous infusion of rituximab. Treatment is
      distinct from the treatment of MS and some of the immunomodulatory drugs commonly
      used in MS can lead to worsening of neuromyelitis optica. INTERPRETATION: The
      condition is an important differential diagnosis of MS, but differs from MS in
      terms of clinical features, prognosis and treatment. Patients have a high risk of
      sequelae following relapses, and therefore early diagnosis and treatment is
      important.

PMID- 24129538
TI  - [Oxygen to premature births--a new scandal?].

PMID- 24129539
TI  - [The terminology newsletter--also for physicians].

PMID- 24129541
TI  - Value of fusion of PET and MRI in the detection of intra-pelvic recurrence of
      gynecological tumor: comparison with 18F-FDG contrast-enhanced PET/CT and pelvic
      MRI.
AB  - BACKGROUND: To evaluate the diagnostic value of retrospective image fusion from
      pelvic magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron
      emission tomography (PET) in detecting intra-pelvic recurrence of gynecological
      tumor. METHODS: Thirty patients with a suspicion of recurrence of gynecological
      malignancy underwent inline contrast-enhanced PET/computed tomography (CT) and
      pelvic contrast-enhanced MRI for restaging. Diagnostic performance about the
      local recurrence, pelvic lymph node and bone metastasis and peritoneal lesion of
      PET/low-dose non-enhanced CT (PET/ldCT), PET/full-dose contrast-enhanced CT
      (PET/ceCT), contrast-enhanced MRI, and retrospective image fusion from PET and
      MRI (fused PET/MRI) were evaluated by two experienced readers. Final diagnoses
      were obtained by histopathological examinations, radiological imaging and
      clinical follow-up for at least 6 months. McNemar test was employed for
      statistical analysis. RESULTS: Documented positive locally recurrent disease,
      pelvic lymph node and bone metastases, and peritoneal dissemination were present
      in 53.3, 26.7, 10.0, and 16.7%, respectively. Patient-based sensitivity for
      detecting local recurrence, pelvic lymph node and bone metastasis and peritoneal
      lesion were 87.5, 87.5, 100 and 80.0%, respectively, for fused PET/MRI, 87.5,
      62.5, 66.7 and 60.0%, respectively, for contrast-enhanced MRI, 62.5, 87.5, 66.7
      and 80.0%, respectively, for PET/ceCT, and 50.0, 87.5, 66.7 and 60.0%,
      respectively, for PET/ldCT. The sensitivity of diagnosing local recurrence by
      fused PET/MRI was significantly better than that of PET/ldCT (p=0.041). The
      patient-based sensitivity, specificity and accuracy for the detection of intra
      pelvic recurrence/metastasis were 91.3, 100 and 93.3% for fused PET/MRI, 82.6,
      100 and 86.7% for contrast-enhanced MRI, 82.6, 100 and 86.7% for PET/ceCT and
      78.3, 85.7 and 80.0% for PET/ldCT. CONCLUSION: Fused PET/MRI combines the
      individual advantages of MRI and PET, and is a valuable technique for assessment
      of intra-pelvic recurrence of gynecological cancers.

PMID- 24129542
TI  - Aerobic intensity and pacing pattern during the six-minute walk test in patients
      with multiple sclerosis.
AB  - OBJECTIVE: To examine the aerobic intensity level and pacing pattern during the 6
      min walk test (6MWT) in persons with multiple sclerosis, taking into account time
      of day, fatigue, disability level and multiple sclerosis subtype. DESIGN: Cross
      sectional study. SUBJECTS/PATIENTS: Eighty multiple sclerosis patients (Expanded
      Disability Status Scale, EDSS <= 6.5). METHODS: Participants performed the 6MWT
      at 3 different time-points (morning, noon, afternoon) during 1 day. Heart rate
      and pacing strategy (distance covered every minute) were registered. A sub-group
      analysis determined the effects of fatigue, disability level and multiple
      sclerosis subtype. RESULTS: The relative aerobic intensity was constant
      throughout the day (67 +/- 10% of estimated maximal heart rate). In all sub
      groups heart rate increased and distance walked declined after the first minute
      (p < 0.001). The mild EDSS sub-group showed a slightly larger increase throughout
      the 6MWT in heart rate development, while no differences were seen in sub-groups
      of fatigue and multiple sclerosis subtype. In most sub-groups walking speed was
      fastest in the first minute and constant during the final 4 minutes. CONCLUSION:
      In patients with multiple sclerosis aerobic intensity is moderate during the 6MWT
      and unaffected by time of day. Disability may have some influence on aerobic
      intensity, but not on pacing strategy during the 6MWT, whereas neither fatigue
      nor multiple sclerosis subtype has any effect.

PMID- 24129543
TI  - Somatic complaints in anxious youth.
AB  - This study examined (a) demographic and clinical characteristics associated with
      physical symptoms in anxiety-disordered youth and (b) the impact of cognitive
      behavioral therapy (Coping Cat), medication (sertraline), their combination, and
      pill placebo on physical symptoms. Youth (N = 488, ages 7-17 years) with a
      principal diagnosis of generalized anxiety disorder, separation anxiety disorder,
      or social phobia participated as part of a multi-site, randomized controlled
      trial and received treatment delivered over 12 weeks. Diagnostic status, symptom
      severity, and impairment were assessed at baseline and week 12. The total number
      and severity of physical symptoms was associated with age, principal diagnosis,
      anxiety severity, impairment, and the presence of comorbid internalizing
      disorders. Common somatic complaints were headaches, stomachaches, head cold or
      sniffles, sleeplessness, and feeling drowsy or too sleepy. Physical symptoms
      decreased over the course of treatment, and were unrelated to treatment
      condition. Clinical implications and directions for future research are discussed
      (ClinicalTrials.gov number, NCT00052078).

PMID- 24129544
TI  - Validation of a patient-centered, culturally sensitive, clinic environment
      inventory using a national sample of adult patients.
AB  - The purpose of this study was to determine the factor structure, internal
      consistency reliability, and validity of the Tucker Culturally Sensitive Health
      Care Clinic Environment Inventory-Patient Form (T-CSHCCEI-PF), a novel instrument
      designed to assess an aspect of health care often ignored in health care quality
      research: the cultural sensitivity of health care center policies and environment
      as perceived by adult, racially/ethnically diverse patients. Using ratings on
      this inventory by a culturally diverse national sample of adult patients (N =
      1,639) from 67 health care sites across the United States, a confirmatory factor
      analysis of the T-CSHCCEI-PF was conducted, and its reliability and validity were
      determined. The T-CSHCCEI-PF was shown to be a reliable and valid inventory for
      culturally diverse patients to provide feedback to the administrators at their
      health care centers regarding the degree to which these centers have
      characteristics that are reflective of patient-centered culturally sensitive
      health care. 

PMID- 24129545
TI  - Promoting charge-separation in p-type dye-sensitized solar cells using bodipy.
AB  - The viability of applying bodipy sensitisers to NiO-based p-type dye-sensitised
      solar cells (p-DSCs) has been successfully demonstrated. The triphenylamine donor
      bodipy acceptor design promotes a long-lived charge-separated state which is
      difficult to achieve with NiO-based devices. The current was above 3 mA cm(-2)
      and the IPCE was 28%. 

PMID- 24129547
TI  - Liverpool care pathway offers no added benefits over usual care for dying
      patients, finds study.

PMID- 24129546
TI  - Correlation between the prognostic value and the expression of the stem cell
      marker CD133 and isocitrate dehydrogenase1 in glioblastomas.
AB  - Cancer stem cells are thought to be responsible for tumor recurrence and
      resistance in glioblastomas. An isocitrate dehydrogenase1 (IDH1) mutation,
      affecting codon132 of the isocitrate dehydrogenase1 gene, has prognostic
      significance in glioblastomas. We investigated whether stem cell marker
      expression [CD133, CD34, and vascular endothelial growth factor (VEGF)] and IDH1
      mutation correlate with clinical factors and prognosis in glioblastoma. CD133,
      CD34, and VEGF expression was evaluated by immunohistochemistry in 67 cases of
      glioblastoma identified between 2005 and 2012. IDH1 mutation was assessed by
      immunohistochemistry, peptide-nucleic-acid mediated PCR clamping, and direct gene
      sequencing. Diffuse CD133 expression was detected in 12 (17.9 %) cases and was
      associated with poor overall survival (OS) (P = 0.010) and progression-free
      survival (P = 0.017). CD34 and VEGF expression were not associated with prognosis
      in these samples. IDH1 mutation was detected in ten (14.9 %) cases. Eight were
      clinically secondary tumors and two were primary tumors (P < 0.001); the mean age
      of the secondary tumor patients was significantly younger (P = 0.001, 41.20 vs.
      59.14). IDH1-positive patients had longer OS than IDH1-negative patients (25.78
      vs. 22.95 months), but this difference was not significant. In addition, IDH1 and
      CD34 expression showed a negative correlation (P = 0.024). Multivariate analysis
      showed that age, extent of surgery, and diffuse CD133 expression correlated with
      OS. CD133 may be a survival marker for glioblastoma. Further characterization of
      CD133, IDH1, and vascular markers in glioblastoma may help identify new
      therapeutic targets.

PMID- 24129548
TI  - Pd(II)-catalyzed direct C-H acylation of N-Boc hydrazones with aldehydes: one-pot
      synthesis of 1,2-diacylbenzenes.
AB  - A palladium(II)-catalyzed direct acylation of acetophenone N-Boc hydrazones with
      aldehydes via C-H bond activation is described. This protocol provides direct
      access to a range of 1,2-diacylbenzenes, which are useful precursors to construct
      biologically interesting and pharmaceutically important compounds.

PMID- 24129550
TI  - Hp(3)/Phi conversion coefficients for neutrons: discussion on the basis of the
      new ICRP recommended limit for the eye lens.
AB  - The new recommendation issued by the International Commission on Radiological
      Protection (ICRP) introducing a 20-mSv annual dose limit for the eye lens
      stimulated an interesting debate among the radiation protection community. In the
      present work the problem of estimating Hp(3) for neutron realistic workplace
      spectra is treated, employing the recently published Hp(3)/Phi conversion
      coefficients with the aim of establishing a workplace-dependent relationship
      between Hp(10) and Hp(3). The results demonstrate that, whilst the two quantities
      can differ by less than 10 %, in general, Hp(10) cannot be considered a
      conservative estimate of Hp(3). 

PMID- 24129551
TI  - Lectin pathway of complement activation and relation with clinical complications
      in critically ill children.
AB  - BACKGROUND: Critically ill children are susceptible to nosocomial infections,
      which contribute to adverse outcomes. Deficiencies in the innate immunity lectin
      pathway of complement activation are implicated in a child's vulnerability to
      infections in conditions such as cancer, but the role during critical illness
      remains unclear. We hypothesized that low on-admission levels of the pathway
      proteins are, in part, genetically determined and associated with susceptibility
      to infectious complications and adverse outcomes. METHODS: We studied protein
      levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL
      associated-serine proteases (MASPs) and MBL-associated protein (MAp44), and
      relation with functional genetic polymorphisms, in 130 healthy children and upon
      intensive care unit (ICU) admission in 700 critically ill children of a
      randomized study on glycemic control. RESULTS: Levels of MASP-1, MASP-2, MASP-3,
      and MAp-44 were lower and the levels of M-ficolin were higher in ICU patients on
      admission than those in matched healthy controls. Only a low on-admission MASP-3
      level was independently associated with risk of new ICU infections and prolonged
      ICU stay, after correcting for other risk factors. On-admission MASP-3 varied
      with age, illness severity, and genetic variation. CONCLUSION: Low on-admission
      MASP-3 levels in critically ill children were independently associated with
      subsequent acquisition of infection and prolonged ICU stay. The biological
      explanation needs further investigation.

PMID- 24129552
TI  - Lean mass, not fat mass, is associated with lung function in male and female
      children with asthma.
AB  - BACKGROUND: Whether body composition is associated with lung function in
      asthmatic children has not been investigated. This study aimed to primarily
      investigate whether BMI z-score and body composition were associated with
      respiratory function in asthmatic children. METHODS: In a cross-sectional study,
      male (n = 27; mean age: 11.9 y (SD: 2.3)) and female (n = 21; mean age: 13.6 y
      (SD: 2.2)) asthmatic children underwent clinical assessment. RESULTS: BMI z-score
      was associated with forced expiratory volume in 1 s (FEV1; r = 0.458), forced
      vital capacity (FVC; r = 0.477), and total lung capacity (TLC; r = 0.451) in
      males only (P < 0.05). Total lean mass was associated with FEV1 (r = 0.655), FVC
      (r = 0.562), and TLC (r = 0.635) in males, as was thoracic lean mass (FEV1 (r =
      0.573), FVC (r = 0.526), and TLC (r = 0.497); P < 0.05). TLC was associated with
      total (r = 0.522) and thoracic (r = 0.532) lean mass in females (P < 0.05). Fat
      mass was not associated with lung function in this group. CONCLUSION: Lean mass,
      not fat mass, is associated with lung function in children with asthma. The
      positive association between BMI z-score and respiratory function in male
      children is driven by lean mass. Although body weight can be easily monitored in
      the clinical setting, body composition can provide important information. Future
      research exploring lean mass and lung function associations could inform future
      interventions.

PMID- 24129553
TI  - Modulation of EEG spectral edge frequency during patterned pneumatic oral
      stimulation in preterm infants.
AB  - BACKGROUND: Stimulation of the nervous system plays a central role in brain
      development and neurodevelopmental outcomes. Thalamocortical and corticocortical
      development is diminished in premature infants and correlated to
      electroencephalography (EEG) progression. The purpose of this study was to
      determine the effects of orocutaneous stimulation on the modulation of spectral
      edge frequency fc = 90% (SEF-90), which is derived from EEG recordings in preterm
      infants. METHODS: A total of 22 preterm infants were randomized to experimental
      and control conditions. Pulsed orocutaneous stimulation was presented during
      gavage feedings begun at ~32 wk postmenstrual age. The SEF-90 was derived from
      two-channel EEG recordings. RESULTS: Compared with the control condition, the
      pulsed orocutaneous stimulation produced a significant reorganization of SEF-90
      in the left (P = 0.005) and right (P < 0.0001) hemispheres. Notably, the left and
      right hemispheres showed a reversal in the polarity of frequency shift,
      demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous
      stimulation also produced a significant pattern of short-term cortical adaptation
      and a long-term neural adaptation manifested as a 0.5 Hz elevation in SEF-90
      after repeated stimulation sessions. CONCLUSION: This is the first study to
      demonstrate the modulating effects of a servo-controlled oral somatosensory input
      on the spectral features of EEG activity in preterm infants.

PMID- 24129554
TI  - Mechanical adaptability of the Bouligand-type structure in natural dermal armour.
AB  - Arapaima gigas, a fresh water fish found in the Amazon Basin, resist predation by
      piranhas through the strength and toughness of their scales, which act as natural
      dermal armour. Arapaima scales consist of a hard, mineralized outer shell
      surrounding a more ductile core. This core region is composed of aligned
      mineralized collagen fibrils arranged in distinct lamellae. Here we show how the
      Bouligand-type (twisted plywood) arrangement of collagen fibril lamellae has a
      key role in developing their unique protective properties, by using in situ
      synchrotron small-angle X-ray scattering during mechanical tensile tests to
      observe deformation mechanisms in the fibrils. Specifically, the Bouligand-type
      structure allows the lamellae to reorient in response to the loading environment;
      remarkably, most lamellae reorient towards the tensile axis and deform in tension
      through stretching/sliding mechanisms, whereas other lamellae sympathetically
      rotate away from the tensile axis and compress, thereby enhancing the scale's
      ductility and toughness to prevent fracture. 

PMID- 24129555
TI  - Surveillance of the first case of human avian influenza A (H7N9) virus in
      Beijing, China.
AB  - PURPOSE: Human infections with avian influenza A (H7N9) virus manifested in China
      in March 2013. The first case infected with H7N9 virus in Beijing involved a
      family member of a chicken dealer and was reported in April 2013. The clinical
      and epidemiological characteristics of this case and her parents were examined to
      illustrate some key traits regarding this novel H7N9 virus. METHODS: The index
      case was subjected to intensive clinical examination in order to observed the
      clinical process. Real-time PCR was used to confirm cases infected with H7N9
      virus. The index case was administered oseltamivir (45 mg, twice daily) at the
      early stage of the infection. Sera were collected from the index case and her
      parents from the onset of illness onwards. The subjects were followed for 4
      weeks. RESULTS: The sera were confirmed by neutralizing antibody tests. The index
      case's clinical manifestation progressed quickly. The pharyngeal swab tested
      positive for influenza A based on the detection of influenza A antigen (rapid
      influenza diagnostic test) 15 h after the onset of fever and was positive for
      H7N9 virus. The patient's temperature dropped to 36.2  degrees C 18 h after
      treatment by oseltamivir (32 h after fever). Cough and other symptoms alleviated
      rapidly. A number of specimens from the environment of this cluster and from the
      feces specimens tested positive for viral RNA of the H7N9 virus on the fourth day
      following onset of the index case's illness. Pharyngeal swabs of the mother
      tested positive for H7N9 virus twice, but she showed no clinical symptoms. Four
      weeks after disease onset, the family did not present any clinical symptoms, and
      the results of the physical examination and blood tests were normal. The mother
      and the case's sera had a fourfold increased neutralizing antibody titer.
      CONCLUSION: Early diagnosis and early initiation of the treatment of confirmed
      infections is the most effective strategy for managing H7N9 virus infection.
      Human beings exposed to H7N9 virus may develop asymptomatic infection.

PMID- 24129556
TI  - Genetic associations in diabetic nephropathy.
AB  - Diabetic nephropathy is a complex disease, caused by both environmental and
      genetic factors. As in most complex diseases, genetic association studies in
      diabetic nephropathy showed inconsistent results. In retrospect, studies with
      small sample sizes, given what are now known to be small odds ratios, were
      partially responsible for this poor replication record. Furthermore, the low
      prior probability in complex genetics and multiple testing played a role. Results
      become more consistent when one only considers those that were replicated. In a
      large meta-analysis study including only replicated associated genetic variants,
      24 genetic variants in 16 genes were found to be associated with diabetic
      nephropathy. These genetic variants may provide novel biological insight. In
      particular, rare variants with a large effect found by hypothesis-free approaches
      (genome-wide association scans, next-generation sequencing) may open new avenues
      of discovery. 

PMID- 24129557
TI  - Causes and consequences of lipoprotein(a) abnormalities in kidney disease.
AB  - Lipoprotein(a) is one of the strongest genetically determined risk factors for
      cardiovascular disease, and patients with chronic kidney disease have major
      disturbances in lipoprotein(a) metabolism. Concentrations are increased and are
      influenced by glomerular filtration rate (GFR) and the amount of proteinuria. The
      reason for this elevation can be increased synthesis, as is the case for patients
      with nephrotic syndrome or those treated by peritoneal dialysis. In hemodialysis
      patients, a catabolic block is the reason for this elevation. The elevated
      concentrations might contribute to the tremendous cardiovascular risk in this
      particular population. In particular, the genetically determined small
      apolipoprotein(a) isoforms are associated with an increased risk for
      cardiovascular events and total mortality. 

PMID- 24129559
TI  - In vivo kinetic studies to further understand pathogenesis of abnormal
      lipoprotein metabolism in chronic kidney disease.
AB  - Patients undergoing hemodialysis (HD) have been shown to be at increased risk for
      cardiovascular disease (CVD) morbidity and mortality which are, at least in part,
      due to uremic dyslipidemia including increased triglyceride-rich lipoproteins, in
      particular remnants, decreased high-density lipoprotein (HDL), and increased
      lipoprotein(a) [Lp(a)]. In vivo kinetic studies using stable isotope revealed
      that apolipoprotein (apo)A-I, a primary apoprotein constitute of HDL, was
      catabolized at a faster rate in HD patients, leading to decreased apoA-I, and
      therefore reduced HDL cholesterol concentrations. Likewise, apoB catabolic rates
      were significantly lower in intermediate-density lipoprotein (IDL) and low
      density lipoprotein (LDL) apoB; the latter is also accompanied by a decreased
      production rate. In HD patients, IDL apoB levels were elevated, but LDL apoB
      levels remained within the normal range. Nonetheless, a prolonged residence time
      for LDL apoB of 2-5 days, made LDL more atherogenic. Atorvastatin completely
      ameliorated impaired LDL apoB catabolism. With regard to Lp(a) metabolism, both
      apoB and apo(a) were found to be slowly catabolized, indicating roles of normal
      kidney function on Lp(a) catabolism. Finally, a compartmental model suggests
      intracellular, rather than extracellular, assembly of Lp(a). This in vivo kinetic
      evidence will uncover the underlying mechanism for uremic dyslipidemia and
      provide strategies to reduce CVD in HD patients.

PMID- 24129558
TI  - Dynamic regulation and dysregulation of the water channel aquaporin-2: a common
      cause of and promising therapeutic target for water balance disorders.
AB  - The human body is two-thirds water. The ability of ensuring the proper amount of
      water inside the body is essential for the survival of mammals. The key event for
      maintenance of body water balance is water reabsorption in the kidney collecting
      ducts, which is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is
      exclusively selective for water molecules and never allows permeation of ions or
      other small molecules. Under normal conditions, AQP2 is restricted within the
      cytoplasm of the collecting duct cells. However, when the body is dehydrated and
      needs to retain water, AQP2 relocates to the apical membrane, allowing water
      reabsorption from the urinary tubule into the cell. Its impairments result in
      various water balance disorders including diabetes insipidus, which is a disease
      characterized by a massive loss of water through the kidney, leading to severe
      dehydration in the body. Dysregulation of AQP2 is also a common cause of water
      retention and hyponatremia that exacerbate the prognosis of congestive heart
      failure and hepatic cirrhosis. Many studies have uncovered the regulation
      mechanisms of AQP2 at the single-molecule level, the whole-body level, and the
      clinical level. In clinical practice, urinary AQP2 is a useful marker for body
      water balance (hydration status). Moreover, AQP2 is now attracting considerable
      attention as a potential therapeutic target for water balance disorders which
      commonly occur in many diseases. 

PMID- 24129560
TI  - Pathology of glomerular lipidosis.
AB  - Glomerular lipid deposition is sometimes associated with a particular kind of
      lipid metabolism disturbance. Ultrastructural analyses using electron microscopy
      often indicate a disease-specific aspect of intraglomerular lipid distribution. 

PMID- 24129561
TI  - Postural alignment in children with bilateral spastic cerebral palsy using a
      bimanual interface for powered wheelchair control.
AB  - OBJECTIVE: To examine postural alignment in children with bilateral spastic
      cerebral palsy while driving a powered wheelchair using both a unilateral
      joystick and an innovative bimanual interface. DESIGN: Cross-sectional study.
      SUBJECTS: A total of 20 children with bilateral spastic cerebral palsy (mean age
      9.0 years (standard deviation 2.1); 11 with diplegia, 9 with quadriplegia) and 14
      typically developing children (mean age 7.7 years (standard deviation 2.9)).
      METHODS: All children drove the powered wheelchair in both the unilateral and
      bimanual conditions. The Seated Postural Control Measure quantified the postural
      alignment of subjects while driving the powered wheelchair. Statistical analysis
      was carried out using repeated measures analysis of variance and Spearman's rank
      correlation coefficient. RESULTS: As expected, typically developing children had
      better postural alignment in both driving conditions than children with cerebral
      palsy. Children with cerebral palsy demonstrated more symmetrical postural
      alignment while using the bimanual interface than when using the unilateral
      joystick. In addition, the severity of cerebral palsy correlated moderately with
      postural symmetry in both conditions. CONCLUSION: The results suggest that this
      innovative bimanual interface might be beneficial for promoting symmetrical
      postural alignment in some children with bilateral spastic cerebral palsy.

PMID- 24129562
TI  - Integrin CD11c/CD18 alpha-chain phosphorylation is functionally important.
AB  - CD11c/CD18 (alphaXbeta2, p150/95, or complement receptor 4, CR4) is a
      monocyte/macrophage-enriched integrin that has been reported to bind to a variety
      of ligands. These include cell surface proteins, extracellular matrix proteins,
      and soluble ligands. The regulation of ligand binding to CD11c/CD18 has remained
      poorly understood. Previous work has shown that both alpha-chain and beta-chain
      phosphorylations of CD11a/CD18 and CD11b/CD18 are needed for activity, but no
      corresponding studies on CD11c/CD18 have been performed. In this study, we have
      identified the phosphorylation site of CD11c as Ser-1158 and show that it is
      pivotal for adherence and phagocytosis. 

PMID- 24129563
TI  - Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc
      modification of transcription factor Sp1.
AB  - Pancreatic cancer, the fourth most prevalent cancer-related cause of death in the
      United States, is a disease with a dismal survival rate of 5% 5 years after
      diagnosis. One of the survival proteins responsible for its extraordinary ability
      to evade cell death is HSP70. A naturally derived compound, triptolide, and its
      water-soluble prodrug, Minnelide, down-regulate the expression of this protein in
      pancreatic cancer cells, thereby causing cell death. However, the mechanism of
      action of triptolide has not been elucidated. Our study shows that triptolide
      induced down-regulation of HSP70 expression is associated with a decrease in
      glycosylation of the transcription factor Sp1. We further show that triptolide
      inhibits glycosylation of Sp1, inhibiting the hexosamine biosynthesis pathway,
      particularly the enzyme O-GlcNAc transferase. Inhibition of O-GlcNAc transferase
      prevents nuclear localization of Sp1 and affects its DNA binding activity. This
      in turn down-regulates prosurvival pathways like NF-kappaB, leading to inhibition
      of HSF1 and HSP70 and eventually to cell death. In this study, we evaluated the
      mechanism by which triptolide affects glycosylation of Sp1, which in turn affects
      downstream pathways controlling survival of pancreatic cancer cells. 

PMID- 24129564
TI  - The Cdc42/Rac nucleotide exchange factor protein beta1Pix (Pak-interacting
      exchange factor) modulates beta-catenin transcriptional activity in colon cancer
      cells: evidence for direct interaction of beta1PIX with beta-catenin.
AB  - Wnt/beta-catenin signaling is highly regulated and critical for intestinal
      epithelial development and repair; aberrant beta-catenin signaling is strongly
      associated with colon cancer. The small GTPase Rac1 regulates beta-catenin
      nuclear translocation and signaling. Here we tested the hypothesis that beta1Pix,
      a Cdc42/Rac guanine nucleotide exchange factor (GEF), regulates beta-catenin
      dependent transcriptional activity and cell function. We report the novel
      observations that beta1Pix binds directly to beta-catenin, an action requiring
      both the beta1Pix DH and dimerization domains but not beta1Pix GEF activity. In
      human colon cancer cells, activation of beta-catenin signaling with LiCl
      decreased beta1Pix/beta-catenin association in the cytosol and increased nuclear
      binding of beta-catenin to beta1Pix. Nuclear association of beta1Pix and beta
      catenin was independent of Rac1 expression and activation; down- and up
      regulating Rac1 expression levels did not alter nuclear beta1Pix/beta-catenin
      association. Ectopic beta1Pix expression enhanced LiCl-induced beta-catenin
      transcriptional activity. Conversely, siRNA knockdown of beta1Pix attenuated both
      LiCl-induced beta-catenin transcriptional activity and colon cancer cell
      proliferation. Ectopic expression of beta1Pix stimulated beta-catenin
      transcriptional activity, whereas beta1PixDelta(602-611), which is unable to bind
      beta-catenin, had no effect. Altogether, these findings suggest that beta1Pix
      functions as a transcriptional regulator of beta-catenin signaling through direct
      interaction with beta-catenin, an action that may be functionally relevant to
      colon cancer biology. 

PMID- 24129565
TI  - Oral administration of transforming growth factor-beta1 (TGF-beta1) protects the
      immature gut from injury via Smad protein-dependent suppression of epithelial
      nuclear factor kappaB (NF-kappaB) signaling and proinflammatory cytokine
      production.
AB  - Inflammatory immune responses play an important role in mucosal homeostasis and
      gut diseases. Nuclear factor kappaB (NF-kappaB), central to the proinflammatory
      cascade, is activated in necrotizing enterocolitis (NEC), a devastating condition
      of intestinal injury with extensive inflammation in premature infants. TGF-beta
      is a strong immune suppressor and a factor in breast milk, which has been shown
      to be protective against NEC. In an NEC animal model, oral administration of the
      isoform TGF-beta1 activated the downstream effector Smad2 in intestine and
      significantly reduced NEC incidence. In addition, TGF-beta1 suppressed NF-kappaB
      activation, maintained levels of the NF-kappaB inhibitor IkappaBalpha in the
      intestinal epithelium, and systemically decreased serum levels of IL-6 and IFN
      gamma. The immature human fetal intestinal epithelial cell line H4 was used as a
      reductionistic model of the immature enterocyte to investigate mechanism. TGF
      beta1 pretreatment inhibited the TNF-alpha-induced IkappaBalpha phosphorylation
      that targets the IkappaBalpha protein for degradation and inhibited NF-kappaB
      activation. Chromatin immunoprecipitation (ChIP) assays demonstrated decreased NF
      kappaB binding to the promoters of IL-6, IL-8, and IkappaBalpha in response to
      TNF-alpha with TGF-beta1 pretreatment. These TGF-beta1 effects appear to be
      mediated through the canonical Smad pathway as silencing of the TGF-beta central
      mediator Smad4 resulted in loss of the TGF-beta1 effects. Thus, TGF-beta1 is
      capable of eliciting anti-inflammatory effects by inhibiting NF-kappaB
      specifically in the intestinal epithelium as well as by decreasing systemic IL-6
      and IFN-gamma levels. Oral administration of TGF-beta1 therefore can potentially
      be used to protect against gastrointestinal diseases. 

PMID- 24129566
TI  - TROY interacts with Rho guanine nucleotide dissociation inhibitor alpha
      (RhoGDIalpha) to mediate Nogo-induced inhibition of neurite outgrowth.
AB  - TROY can functionally substitute p75 to comprise the Nogo receptor complex, which
      transduces the inhibitory signal of myelin-associated inhibitory factors on axon
      regeneration following CNS injury. The inhibition of neurite extension relies on
      TROY-dependent RhoA activation, but how TROY activates RhoA remains unclear.
      Here, we firstly identified Rho guanine nucleotide dissociation inhibitor alpha
      (RhoGDIalpha) as a binding partner of TROY using GST pull-down combined with two
      dimensional gel electrophoresis and mass spectra analysis. The interaction was
      further confirmed by coimmunoprecipitation in vitro and in vivo. Deletion
      mutagenesis revealed that two regions of the TROY intracellular domain (amino
      acids 234-256 and 321-350) were essential for the interaction with RhoGDIalpha.
      Secondly, TROY and RhoGDIalpha were coexpressed in postnatal dorsal root ganglion
      neurons, cortex neurons, and cerebellar granule neurons (CGNs). Thirdly,
      TROY/RhoGDIalpha association was potentiated by Nogo-66 and was independent of
      p75/RhoGDIalpha interaction. Fourthly, TROY/RhoGDIalpha interaction was still
      able to activate RhoA when p75 was deficient. Furthermore, RhoA activation was
      decreased dramatically when TROY was knocked down in p75-deficient CGNs cells.
      Finally, RhoGDIalpha overexpression abolished RhoA activation and following
      neurite outgrowth inhibition by Nogo-66 in both wild-type and p75-deficient CGNs.
      These results showed that the association of RhoGDIalpha with TROY contributed to
      TROY-dependent RhoA activation and neurite outgrowth inhibition after Nogo-66
      stimulation. 

PMID- 24129567
TI  - Direct inhibition of Gcn5 protein catalytic activity by polyglutamine-expanded
      ataxin-7.
AB  - Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by
      polyglutamine (polyQ) expansion within the N-terminal region of the ataxin-7
      protein, a known subunit of the SAGA complex. Although the mechanisms of SCA7
      pathogenesis remain poorly understood, previous studies have shown perturbations
      in SAGA histone acetyltransferase function and transcriptional alterations. We
      sought to determine whether and how polyQ-expanded ataxin-7 affects SAGA
      catalytic activity. Here, we determined that polyQ-expanded ataxin-7 directly
      bound the Gcn5 catalytic core of SAGA while in association with its regulatory
      proteins, Ada2 and Ada3. This caused a significant decrease in Gcn5 histone
      acetyltransferase activity in vitro and in vivo at two SAGA-regulated galactose
      genes, GAL1 and GAL7. However, Gcn5 occupancy at the GAL1 and GAL7 promoters was
      increased in these cells, revealing a dominant-negative phenotype of the polyQ
      expanded ataxin-7-incorporated, catalytically inactive SAGA. These findings
      suggest a dominant mechanism of polyQ-mediated SAGA inhibition that potentially
      contributes to SCA7 disease pathogenesis. 

PMID- 24129568
TI  - Structure of the Toxoplasma gondii ROP18 kinase domain reveals a second ligand
      binding pocket required for acute virulence.
AB  - At least a third of the human population is infected with the intracellular
      parasite Toxoplasma gondii, which contributes significantly to the disease burden
      in immunocompromised and neutropenic hosts and causes serious congenital
      complications when vertically transmitted to the fetus. Genetic analyses have
      identified the Toxoplasma ROP18 Ser/Thr protein kinase as a major factor
      mediating acute virulence in mice. ROP18 is secreted into the host cell during
      the invasion process, and its catalytic activity is required for the acute
      virulence phenotype. However, its precise molecular function and regulation are
      not fully understood. We have determined the crystal structure of the ROP18
      kinase domain, which is inconsistent with a previously proposed autoinhibitory
      mechanism of regulation. Furthermore, a sucrose molecule bound to our structure
      identifies an additional ligand-binding pocket outside of the active site cleft.
      Mutational analysis confirms an important role for this pocket in virulence. 

PMID- 24129570
TI  - The reaction kinetics of 3-hydroxybenzoate 6-hydroxylase from Rhodococcus jostii
      RHA1 provide an understanding of the para-hydroxylation enzyme catalytic cycle.
AB  - 3-Hydroxybenzoate 6-hydroxylase (3HB6H) from Rhodococcus jostii RHA1 is an NADH
      specific flavoprotein monooxygenase that catalyzes the para-hydroxylation of 3
      hydroxybenzoate (3HB) to form 2,5-dihydroxybenzoate (2,5-DHB). Based on results
      from stopped-flow spectrophotometry, the reduced enzyme-3HB complex reacts with
      oxygen to form a C4a-peroxy flavin with a rate constant of 1.13 +/- 0.01 * 10(6)
      m(-1) s(-1) (pH 8.0, 4  degrees C). This intermediate is subsequently protonated
      to form a C4a-hydroperoxyflavin with a rate constant of 96 +/- 3 s(-1). This step
      shows a solvent kinetic isotope effect of 1.7. Based on rapid-quench
      measurements, the hydroxylation occurs with a rate constant of 36 +/- 2 s(-1).
      3HB6H does not exhibit substrate inhibition on the flavin oxidation step, a
      common characteristic found in most ortho-hydroxylation enzymes. The apparent
      kcat at saturating concentrations of 3HB, NADH, and oxygen is 6.49 +/- 0.02 s(
      1). Pre-steady state and steady-state kinetic data were used to construct the
      catalytic cycle of the reaction. The data indicate that the steps of product
      release (11.7 s(-1)) and hydroxylation (36 +/- 2 s(-1)) partially control the
      overall turnover. 

PMID- 24129569
TI  - LRP1 assembles unique co-receptor systems to initiate cell signaling in response
      to tissue-type plasminogen activator and myelin-associated glycoprotein.
AB  - In addition to functioning as an activator of fibrinolysis, tissue-type
      plasminogen activator (tPA) interacts with neurons and regulates multiple aspects
      of neuronal cell physiology. In this study, we examined the mechanism by which
      tPA initiates cell signaling in PC12 and N2a neuron-like cells. We demonstrate
      that enzymatically active and inactive tPA (EI-tPA) activate ERK1/2 in a biphasic
      manner. Rapid ERK1/2 activation is dependent on LDL receptor-related protein-1
      (LRP1). In the second phase, ERK1/2 is activated by tPA independently of LRP1.
      The length of the LRP1-dependent phase varied inversely with the tPA
      concentration. Rapid ERK1/2 activation in response to EI-tPA and activated alpha2
      macroglobulin (alpha2M*) required the NMDA receptor and Trk receptors, which
      assemble with LRP1 into a single pathway. Assembly of this signaling system may
      have been facilitated by the bifunctional adapter protein, PSD-95, which
      associated with LRP1 selectively in cells treated with EI-tPA or alpha2M*. Myelin
      associated glycoprotein binds to LRP1 with high affinity but failed to induce
      phosphorylation of TrkA or ERK1/2. Instead, myelin-associated glycoprotein
      recruited p75 neurotrophin receptor (p75NTR) into a complex with LRP1 and
      activated RhoA. p75NTR was not recruited by other LRP1 ligands, including EI-tPA
      and alpha2M*. Lactoferrin functioned as an LRP1 signaling antagonist, inhibiting
      Trk receptor phosphorylation and ERK1/2 activation in response to EI-tPA. These
      results demonstrate that LRP1-initiated cell signaling is ligand-dependent.
      Proteins that activate cell signaling by binding to LRP1 assemble different co
      receptor systems. Ligand-specific co-receptor recruitment provides a mechanism by
      which one receptor, LRP1, may trigger different signaling responses. 

PMID- 24129571
TI  - Interaction between salt-inducible kinase 2 (SIK2) and p97/valosin-containing
      protein (VCP) regulates endoplasmic reticulum (ER)-associated protein degradation
      in mammalian cells.
AB  - Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element
      binding protein-mediated gene expression in various cell types and is the only
      AMP-activated protein kinase family member known to interact with the p97/valosin
      containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can
      regulate autophagy when proteasomal function is compromised. Here we report that
      physical and functional interactions between SIK2 and p97/VCP underlie the
      regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD).
      SIK2 co-localizes with p97/VCP in the ER membrane and stimulates its ATPase
      activity through direct phosphorylation. Although the expression of wild-type
      recombinant SIK2 accelerated the degradation and removal of ERAD substrates, the
      kinase-deficient variant conversely had no effect. Furthermore, down-regulation
      of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired
      degradation of ERAD substrates and disruption of ER homeostasis. Collectively,
      these findings highlight a mechanism by which the interplay between SIK2 and
      p97/VCP contributes to the regulation of ERAD in mammalian cells. 

PMID- 24129572
TI  - Retinal pigmented epithelial cells obtained from human induced pluripotent stem
      cells possess functional visual cycle enzymes in vitro and in vivo.
AB  - Differentiated retinal pigmented epithelial (RPE) cells have been obtained from
      human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle
      in hiPS-RPE cells has not been adequately examined. Here we determined the
      expression of functional visual cycle enzymes in hiPS-RPE cells compared with
      that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo.
      hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably,
      expression of certain visual cycle proteins was maintained during cell culture of
      hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in
      mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome
      formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with
      luciferase activity were transplanted into the subretinal space of mice,
      bioluminance intensity was preserved for >3 months. Additionally, transplantation
      of mpRPE into blind Lrat(-/-) and Rpe65(-/-) mice resulted in the recovery of
      visual function, including increased electrographic signaling and endogenous 11
      cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the
      subretinal space of Lrat(-/-) and Rpe65(-/-) mice, their vision improved as well.
      Moreover, histological analyses of these eyes displayed replacement of
      dysfunctional RPE cells by hiPS-RPE cells. Together, our results show that hiPS
      RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells
      could provide potential treatment options for certain blinding retinal
      degenerative diseases. 

PMID- 24129573
TI  - Negative regulation of interferon-induced transmembrane protein 3 by SET7
      mediated lysine monomethylation.
AB  - Although lysine methylation is classically known to regulate histone function,
      its role in modulating antiviral restriction factor activity remains
      uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found
      monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral
      activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis
      virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting
      the interaction between IFITM3 and SET7, suggesting that this pathway could be
      hijacked to support infection; conversely, IFN-alpha reduced IFITM3-K88me1
      levels. These findings may have important implications in the design of
      therapeutics targeting protein methylation against infectious diseases. 

PMID- 24129575
TI  - Hydrolysis at one of the two nucleotide-binding sites drives the dissociation of
      ATP-binding cassette nucleotide-binding domain dimers.
AB  - The functional unit of ATP-binding cassette (ABC) transporters consists of two
      transmembrane domains and two nucleotide-binding domains (NBDs). ATP binding
      elicits association of the two NBDs, forming a dimer in a head-to-tail
      arrangement, with two nucleotides "sandwiched" at the dimer interface. Each of
      the two nucleotide-binding sites is formed by residues from the two NBDs. We
      recently found that the prototypical NBD MJ0796 from Methanocaldococcus
      jannaschii dimerizes in response to ATP binding and dissociates completely
      following ATP hydrolysis. However, it is still unknown whether dissociation of
      NBD dimers follows ATP hydrolysis at one or both nucleotide-binding sites. Here,
      we used luminescence resonance energy transfer to study heterodimers formed by
      one active (donor-labeled) and one catalytically defective (acceptor-labeled)
      NBD. Rapid mixing experiments in a stop-flow chamber showed that NBD heterodimers
      with one functional and one inactive site dissociated at a rate indistinguishable
      from that of dimers with two hydrolysis-competent sites. Comparison of the rates
      of NBD dimer dissociation and ATP hydrolysis indicated that dissociation followed
      hydrolysis of one ATP. We conclude that ATP hydrolysis at one nucleotide-binding
      site drives NBD dimer dissociation. 

PMID- 24129574
TI  - Compartmentalization of distinct cAMP signaling pathways in mammalian sperm.
AB  - Fertilization competence is acquired in the female tract in a process known as
      capacitation. Capacitation is needed for the activation of motility (e.g.
      hyperactivation) and to prepare the sperm for an exocytotic process known as
      acrosome reaction. Although the HCO3(-)-dependent soluble adenylyl cyclase Adcy10
      plays a role in motility, less is known about the source of cAMP in the sperm
      head. Transmembrane adenylyl cyclases (tmACs) are another possible source of
      cAMP. These enzymes are regulated by stimulatory heterotrimeric Gs proteins;
      however, the presence of Gs or tmACs in mammalian sperm has been controversial.
      In this study, we used Western blotting and cholera toxin-dependent ADP
      ribosylation to show the Gs presence in the sperm head. Also, we showed that
      forskolin, a tmAC-specific activator, induces cAMP accumulation in sperm from
      both WT and Adcy10-null mice. This increase is blocked by the tmAC inhibitor
      SQ22536 but not by the Adcy10 inhibitor KH7. Although Gs immunoreactivity and
      tmAC activity are detected in the sperm head, PKA is only found in the tail,
      where Adcy10 was previously shown to reside. Consistent with an acrosomal
      localization, Gs reactivity is lost in acrosome-reacted sperm, and forskolin is
      able to increase intracellular Ca(2+) and induce the acrosome reaction.
      Altogether, these data suggest that cAMP pathways are compartmentalized in sperm,
      with Gs and tmAC in the head and Adcy10 and PKA in the flagellum. 

PMID- 24129576
TI  - High accuracy in silico sulfotransferase models.
AB  - Predicting enzymatic behavior in silico is an integral part of our efforts to
      understand biology. Hundreds of millions of compounds lie in targeted in silico
      libraries waiting for their metabolic potential to be discovered. In silico
      "enzymes" capable of accurately determining whether compounds can inhibit or
      react is often the missing piece in this endeavor. This problem has now been
      solved for the cytosolic sulfotransferases (SULTs). SULTs regulate the
      bioactivities of thousands of compounds--endogenous metabolites, drugs and other
      xenobiotics--by transferring the sulfuryl moiety (SO3) from 3'-phosphoadenosine
      5'-phosphosulfate to the hydroxyls and primary amines of these acceptors. SULT1A1
      and 2A1 catalyze the majority of sulfation that occurs during human Phase II
      metabolism. Here, recent insights into the structure and dynamics of SULT binding
      and reactivity are incorporated into in silico models of 1A1 and 2A1 that are
      used to identify substrates and inhibitors in a structurally diverse set of 1,455
      high value compounds: the FDA-approved small molecule drugs. The SULT1A1 models
      predict 76 substrates. Of these, 53 were known substrates. Of the remaining 23,
      21 were tested, and all were sulfated. The SULT2A1 models predict 22 substrates,
      14 of which are known substrates. Of the remaining 8, 4 were tested, and all are
      substrates. The models proved to be 100% accurate in identifying substrates and
      made no false predictions at Kd thresholds of 100 MUM. In total, 23 "new" drug
      substrates were identified, and new linkages to drug inhibitors are predicted. It
      now appears to be possible to accurately predict Phase II sulfonation in silico.

PMID- 24129577
TI  - Multimodal mechanism of action for the Cdc34 acidic loop: a case study for why
      ubiquitin-conjugating enzymes have loops and tails.
AB  - Together with ubiquitin ligases (E3), ubiquitin-conjugating enzymes (E2) are
      charged with the essential task of synthesizing ubiquitin chains onto protein
      substrates. Some 75% of the known E2s in the human proteome contain unique
      insertions in their primary sequences, yet it is largely unclear what effect
      these insertions impart on the ubiquitination reaction. Cdc34 is an important E2
      with prominent roles in cell cycle regulation and signal transduction. The amino
      acid sequence of Cdc34 contains an insertion distal to the active site that is
      absent in most other E2s, yet this acidic loop (named for its four invariably
      conserved acidic residues) is critical for Cdc34 function both in vitro and in
      vivo. Here we have investigated how the acidic loop in human Cdc34 promotes
      ubiquitination, identifying two key molecular events during which the acidic loop
      exerts its influence. First, the acidic loop promotes the interaction between
      Cdc34 and its ubiquitin ligase partner, SCF. Second, two glutamic acid residues
      located on the distal side of the loop collaborate with an invariably conserved
      histidine on the proximal side of the loop to suppress the pKa of an ionizing
      species on ubiquitin or Cdc34 which greatly contributes to Cdc34 catalysis. These
      results demonstrate that insertions can guide E2s to their physiologically
      relevant ubiquitin ligases as well as provide essential modalities that promote
      catalysis. 

PMID- 24129578
TI  - Complementary interhelical interactions between three buried Glu-Lys pairs within
      three heptad repeats are essential for Hec1-Nuf2 heterodimerization and mitotic
      progression.
AB  - Hec1 and Nuf2, core components of the NDC80 complex, are essential for
      kinetochore-microtubule attachment and chromosome segregation. It has been shown
      that both Hec1 and Nuf2 utilize their coiled-coil domains to form a functional
      dimer; however, details of the consequential significance and structural
      requirements to form the dimerization interface have yet to be elucidated. Here,
      we showed that Hec1 required three contiguous heptad repeats from Leu-324 to Leu
      352, but not the entire first coiled-coil domain, to ensure overall stability of
      the NDC80 complex through direct interaction with Nuf2. Substituting the
      hydrophobic core residues, Leu-331, Val-338, and Ile-345, of Hec1 with alanine
      completely eliminated Nuf2 binding and blocked mitotic progression. Moreover,
      unlike most coiled-coil proteins, where the buried positions are composed of
      hydrophobic residues, Hec1 possessed an unusual distribution of glutamic acid
      residues, Glu-334, Glu-341, and Glu-348, buried within the interior dimerization
      interface, which complement with three Nuf2 lysine residues: Lys-227, Lys-234,
      and Lys-241. Substituting these corresponding residues with alanine diminished
      the binding affinity between Hec1 and Nuf2, compromised NDC80 complex formation,
      and adversely affected mitotic progression. Taken together, these findings
      demonstrated that three buried glutamic acid-lysine pairs, in concert with
      hydrophobic interactions of core residues, provide the major specificity and
      stability requirements for Hec1-Nuf2 dimerization and NDC80 complex formation. 

PMID- 24129580
TI  - Photocatalytic reduction of benzonitrile to benzylamine in aqueous suspensions of
      palladium-loaded titanium(IV) oxide.
AB  - Benzonitrile (PhCN) was successfully reduced to benzyl amine in acidic aqueous
      suspensions of a palladium (Pd)-loaded titanium(IV) oxide (TiO2) photocatalyst in
      the presence of oxalic acid as a hole scavenger, although the reduction potential
      of PhCN is believed to be much higher than the potential of the conduction band
      (CB) of TiO2, indicating that a Pd co-catalyst strongly contributes to PhCN
      reduction and that the applicability of photocatalytic reduction is not limited
      by the CB position of semiconductor photocatalysts.

PMID- 24129579
TI  - Model of tryptophan metabolism, readily scalable using tissue-specific gene
      expression data.
AB  - Tryptophan is utilized in various metabolic routes including protein synthesis,
      serotonin, and melatonin synthesis and the kynurenine pathway. Perturbations in
      these pathways have been associated with neurodegenerative diseases and cancer.
      Here we present a comprehensive kinetic model of the complex network of human
      tryptophan metabolism based upon existing kinetic data for all enzymatic
      conversions and transporters. By integrating tissue-specific expression data,
      modeling tryptophan metabolism in liver and brain returned intermediate
      metabolite concentrations in the physiological range. Sensitivity and metabolic
      control analyses identified expected key enzymes to govern fluxes in the branches
      of the network. Combining tissue-specific models revealed a considerable impact
      of the kynurenine pathway in liver on the concentrations of neuroactive
      derivatives in the brain. Moreover, using expression data from a cancer study
      predicted metabolite changes that resembled the experimental observations. We
      conclude that the combination of the kinetic model with expression data
      represents a powerful diagnostic tool to predict alterations in tryptophan
      metabolism. The model is readily scalable to include more tissues, thereby
      enabling assessment of organismal tryptophan metabolism in health and disease. 

PMID- 24129581
TI  - Survey of oral chemotherapy safety and adherence practices of hospitals in Spain.
AB  - BACKGROUND: Oral chemotherapy is increasingly used for cancer therapy but,
      without proper practices, creates safety and adherence issues. However, little is
      known on safety and adherence practices in wide clinical settings. OBJECTIVE: To
      assess the implementation level of safety and adherence practices in oral
      chemotherapy in Spanish hospitals. SETTING: All Pharmacy services from
      prescription, dispensation, patient education and monitoring hospitals that
      prescribe oral chemotherapy of Spain. MAIN OUTCOME MEASURE: Level of safety
      practices regarding oral chemotherapy prescription, dispensation, patient
      education and adherence. METHOD: An 11 multiple-choice-item questionnaire made in
      consensus with GEDEFO (Spanish Group of Oncology Pharmacists) was sent to all
      pharmacy services from hospitals that prescribe oral chemotherapy. This
      questionnaire comprised prescription, dispensation, education and monitoring. We
      arbitrarily defined three levels of practices: no sufficient specific practices
      were reported (we termed this as 'level I'); performance of an initial visit with
      a pharmacist providing written patient educational materials and monitoring
      adherence (termed as 'level II'); and level II requirements plus electronic
      chemotherapy ordering system and extra safety practices (termed as 'level III').
      RESULTS: Of the 169 targeted health-care settings, 86 (50.9 %) responded to the
      survey. The majority of responding hospitals were public, general, and teaching
      hospitals with more than 200 beds. Main discrepancies were in electronic
      prescription of oral chemotherapy and monitoring adherence. There were 32
      hospitals (37.2 %) with level I of safety and adherence practices, 38 hospitals
      (44.2 %) accomplished level II, 16 (18.6 %) hospitals reached level III. No
      hospital variables were found to be correlated with each level of safety.
      CONCLUSIONS: The majority of responding hospitals have safety and adherences
      practices for oral chemotherapy. However, the level of these practices varies.
      There are significant opportunities for improvement, particularly with regard to
      electronic prescription of oral chemotherapy and monitoring adherence.

PMID- 24129583
TI  - On A Nonlinear Generalization of Sparse Coding and Dictionary Learning.
AB  - Existing dictionary learning algorithms are based on the assumption that the data
      are vectors in an Euclidean vector space R d , and the dictionary is learned from
      the training data using the vector space structure of R d and its Euclidean L2
      metric. However, in many applications, features and data often originated from a
      Riemannian manifold that does not support a global linear (vector space)
      structure. Furthermore, the extrinsic viewpoint of existing dictionary learning
      algorithms becomes inappropriate for modeling and incorporating the intrinsic
      geometry of the manifold that is potentially important and critical to the
      application. This paper proposes a novel framework for sparse coding and
      dictionary learning for data on a Riemannian manifold, and it shows that the
      existing sparse coding and dictionary learning methods can be considered as
      special (Euclidean) cases of the more general framework proposed here. We show
      that both the dictionary and sparse coding can be effectively computed for
      several important classes of Riemannian manifolds, and we validate the proposed
      method using two well-known classification problems in computer vision and
      medical imaging analysis.

PMID- 24129582
TI  - Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV
      infection.
AB  - BACKGROUND: There are 34 million people living with human immunodeficiency virus
      (HIV) worldwide and each year this number increases. Until a vaccine is
      discovered, the prevention of new HIV infections remains an urgent priority.
      Several trials studying the use of oral and topical agents for the prevention of
      HIV infection have already been completed. Adherence has proved to be a major
      challenge in achieving product efficacy. AIM OF THE REVIEW: To provide the
      clinical pharmacist with an understanding of the oral pre-exposure prophylaxis
      (PrEP) and topical microbicide product pipeline whilst emphasizing the critical
      importance of adherence to these drugs to avert HIV infection. METHODS:
      PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were
      searched using appropriate key words. For the time period 1992-2013--all phase II
      and phase III safety and effectiveness studies--testing agents for prevention of
      HIV infection were included in the review. Efficacy estimates, adherence
      estimates and reported challenges with adherence were extracted. RESULTS: Twenty
      four phase II and III clinical trials were found during review. Of these, 20
      trials have been completed, and six trials show effectiveness in preventing HIV
      infection. The majority of the successful trials were to oral PrEP and to date
      only one microbicide trial of a vaginal antiretroviral microbicide gel has showed
      effectiveness. Adherence to study product played a major role in trial outcomes
      and there are several reasons for non-adherence. These include high on-trial
      pregnancy rates, low trial retention rates, low participant perception of risk,
      participant characteristics such as age <25 years, single status, migratory
      partners and trial fatigue. Study product characteristics such as dosage form,
      dosing interval, as well as associated adverse events may also influence
      adherence. CONCLUSION: Moderate to high adherence is critical to demonstrate
      efficacy of drugs for HIV prevention. For topical agents, intermittent use
      associated with coitus is more effective than daily use, particularly if sex is
      infrequent or partners migrant. For oral agents, daily use is effective but the
      motivation to use the drug and high risk perception is important. In
      serodiscordant couples, early initiation of highly active antiretroviral therapy
      in the infected partner affords almost complete protection to the negative
      partner. Drugs need to be tailored to the population at risk and availability of
      multiple drug options are important.

PMID- 24129585
TI  - Passivation of nanocrystalline silicon photovoltaic materials employing a
      negative substrate bias.
AB  - Hydrogenated nanocrystalline silicon (nc-Si:H) shows great promise in the
      application of third-generation thin film photovoltaic cells. However, the mixed
      phase structure of nc-Si:H leads to many defects existing in this important solar
      energy material. Here we present a new way to passivate nc-Si:H films by tuning
      the negative substrate bias in plasma-enhanced chemical vapor deposition.
      Microstructures of the nc-Si:H films prepared under a negative bias from 0 to 
      300 V have been characterized using Raman, x-ray diffraction, transmission
      electron microscope, and optical transmission techniques. A novel passivation
      effect on nc-Si:H films has been identified by the volume fraction of voids in nc
      Si:H, together with the electrical properties obtained by electron spin resonance
      and effective minority lifetime measurements. The mechanism of the passivation
      effect has been demonstrated by infrared spectroscopy, which illustrates that the
      high-energy H atoms and ions accelerated by an appropriate bias of -180 V can
      form more hydrides along the grain boundaries and effectively prevent oxygen
      incursions forming further Si-O/Si interface dangling bonds in the nc-Si:H films.
      The detrimental influence of a bias over -180 V on the film quality due to the
      strong ion bombardment of species with excessively high energy has also been
      observed directly from the surface morphology by atomic force microscopy. 

PMID- 24129584
TI  - Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear
      RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS.
AB  - Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are
      devastating neurodegenerative disorders with clinical, genetic, and
      neuropathological overlap. A hexanucleotide (GGGGCC) repeat expansion in a non
      coding region of C9ORF72 is the major genetic cause of both diseases. The
      mechanisms by which this repeat expansion causes "c9FTD/ALS" are not definitively
      known, but RNA-mediated toxicity is a likely culprit. RNA transcripts of the
      expanded GGGGCC repeat form nuclear foci in c9FTD/ALS, and also undergo repeat
      associated non-ATG (RAN) translation resulting in the production of three
      aggregation-prone proteins. The goal of this study was to examine whether
      antisense transcripts resulting from bidirectional transcription of the expanded
      repeat behave in a similar manner. We show that ectopic expression of (CCCCGG)66
      in cultured cells results in foci formation. Using novel polyclonal antibodies
      for the detection of possible (CCCCGG)exp RAN proteins [poly(PR), poly(GP) and
      poly(PA)], we validated that (CCCCGG)66 is also subject to RAN translation in
      transfected cells. Of importance, foci composed of antisense transcripts are
      observed in the frontal cortex, spinal cord and cerebellum of c9FTD/ALS cases,
      and neuronal inclusions of poly(PR), poly(GP) and poly(PA) are present in various
      brain tissues in c9FTD/ALS, but not in other neurodegenerative diseases,
      including CAG repeat disorders. Of note, RNA foci and poly(GP) inclusions
      infrequently co-occur in the same cell, suggesting these events represent two
      distinct ways in which the C9ORF72 repeat expansion may evoke neurotoxic effects.
      These findings provide mechanistic insight into the pathogenesis of c9FTD/ALS,
      and have significant implications for therapeutic strategies.

PMID- 24129586
TI  - Synergistic antibiotic combination powders of colistin and rifampicin provide
      high aerosolization efficiency and moisture protection.
AB  - For many respiratory infections caused by multidrug-resistant Gram-negative
      bacteria, colistin is the only effective antibiotic despite its nephrotoxicity. A
      novel inhaled combination formulation of colistin with a synergistic
      antimicrobial component of rifampicin was prepared via co-spray drying, aiming to
      deliver the drug directly to the respiratory tract and minimize drug resistance
      and adverse effects. Synergistic antibacterial activity against Acinetobacter
      baumannii was demonstrated for the combination formulation with high emitted
      doses (96%) and fine particle fraction total (FPFtotal; 92%). Storage of the
      spray-dried colistin alone formulation in the elevated relative humidity (RH) of
      75% resulted in a substantial deterioration in the aerosolization performance
      because the amorphous colistin powders absorbed significant amount of water up to
      30% by weight. In contrast, the FPFtotal values of the combination formulation
      stored at various RH were unchanged, which was similar to the aerosolization
      behavior of the spray-dried rifampicin-alone formulation. Advanced surface
      chemistry measurements by XPS and ToF-SIMS demonstrated a dominance of rifampicin
      on the combination particle surfaces, which contributed to the moisture
      protection at the elevated RH. This study shows a novel inhalable powder
      formulation of antibiotic combination with the combined beneficial properties of
      synergistic antibacterial activity, high aerosolization efficiency, and moisture
      protection. 

PMID- 24129587
TI  - Barriers and facilitators of a healthy lifestyle among persons with serious and
      persistent mental illness: perspectives of community mental health providers.
AB  - The investigators used qualitative methods to examine perspectives of community
      mental health professionals on obesity management in adults with serious mental
      illness (SMI). Data from 5 focus groups were subjected to constant comparison
      analysis and grounded theory. Results showed that influences at individual,
      social, community, and societal levels impact development and maintenance of
      obesity. Mental health providers desired a collaborative relationship with health
      promotion program staff. They also believed that frequent, group-based health
      promotion should include participation incentives for adults with SMI and should
      occur over durations of at least 6-months to achieve improved health outcomes for
      this population. 

PMID- 24129588
TI  - Low holotranscobalamin and cobalamins predict incident fractures in elderly men:
      the MrOS Sweden.
AB  - In a population-based study on cobalamin status and incident fractures in elderly
      men (n = 790) with an average follow-up of 5.9 years, we found that low levels of
      metabolically active and total cobalamins predict incident fractures,
      independently of body mass index (BMI), bone mineral density (BMD), plasma total
      homocysteine (tHcy), and cystatin C. INTRODUCTION: Cobalamin deficiency in
      elderlies may affect bone metabolism. This study aims to determine whether serum
      cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predict
      incident fractures in old men. METHODS: Men participating in the Gothenburg part
      of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and
      without ongoing vitamin B medication were included in the present study (n = 790;
      age range, 70-81 years). RESULTS: During an average follow-up of 5.9 years, 110
      men sustained X-ray-verified fractures including 45 men with clinical vertebral
      fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls,
      prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and
      physical activity (fully adjusted)), increased per each standard deviation
      decrease in cobalamins (hazard ratio (HR), 1.38; 95% confidence intervals (CI),
      1.11-1.72) and holoTC (HR, 1.26; 95% CI, 1.03-1.54), respectively. Men in the
      lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk
      of all fracture (cobalamins, HR = 1.67 (95% CI, 1.06-2.62); holoTC, HR = 1.74
      (95% CI, 1.12-2.69)) compared with quartiles 2-4. No associations between folate
      or tHcy and incident fractures were seen. CONCLUSIONS: We present novel data
      showing that low levels of holoTC and cobalamins predicting incident fracture in
      elderly men. This association remained after adjustment for BMI, BMD, tHcy, and
      cystatin C. However, any causal relationship between low cobalamin status and
      fractures should be explored in a prospective treatment study.

PMID- 24129589
TI  - Design, synthesis and characterization of novel inhibitors against mycobacterial
      beta-ketoacyl CoA reductase FabG4.
AB  - We report the design and synthesis of triazole-polyphenol hybrid compounds 1 and
      2 as inhibitors of the FabG4 (Rv0242c) enzyme of Mycobacterium tuberculosis for
      the first time. A major advance in this field occurred only a couple of years ago
      with the X-ray crystal structure of FabG4, which has helped us to design these
      inhibitors by the computational fragment-based drug design (FBDD) approach.
      Compound 1 has shown competitive inhibition with an inhibition constant (Ki)
      value of 3.97 +/- 0.02 MUM. On the other hand, compound 2 has been found to be a
      mixed type inhibitor with a Ki value of 0.88 +/- 0.01 MUM. Thermodynamic analysis
      using isothermal titration calorimetry (ITC) reveals that both inhibitors bind at
      the NADH co-factor binding domain. Their MIC values, as determined by resazurin
      assay against M. smegmatis, indicated their good anti-mycobacterial properties. A
      preliminary structure-activity relationship (SAR) study supports the design of
      these inhibitors. These compounds may be possible candidates as lead compounds
      for alternate anti-tubercular drugs. All of the reductase enzymes of the
      Mycobacterium family have a similar ketoacyl reductase (KAR) domain. Hence, this
      work may be extrapolated to find structure-based inhibitors of other reductase
      enzymes. 

PMID- 24129590
TI  - To be or not to be: long-QT syndrome type 9.

PMID- 24129591
TI  - Circulating microRNA profiles for detection of peripheral arterial disease: small
      new biomarkers for cardiovascular disease.

PMID- 24129593
TI  - Exome sequencing in congenital heart disease points to importance of DNA
      methylation.

PMID- 24129592
TI  - Differential microRNA expression profiles in peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a clinical condition caused by
      an atherosclerotic process affecting the arteries of the limbs. Despite major
      improvements in surgical endovascular techniques, PAD is still associated with
      high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short
      noncoding RNA controlling gene expression, have emerged as major regulators of
      multiple biological processes. METHODS AND RESULTS: A whole-miRNA transcriptome
      profiling was performed in peripheral blood from an initial sample set of
      patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e,
      miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was
      further investigated and validated in 2 additional sample sets. Each of these 12
      miRNAs exhibited good diagnostic value as evidenced by receiver operating
      characteristic curve analyses. Pathway enrichment analysis using predicted and
      validated targets identified several signaling pathways relevant to vascular
      disorders. Several of these pathways, including cell adhesion molecules, were
      confirmed by quantifying the expression level of several candidate genes
      regulating the initial stages of the inflammatory atherosclerotic process. The
      expression level of 7 of these candidate genes exhibits striking inverse
      correlation with that of several, if not all, of the miRNAs of the PAD-specific
      miRNA signature. CONCLUSIONS: These results demonstrate the potential of miRNAs
      for the diagnosis of PAD and provide further insight into the molecular
      mechanisms leading to the development of PAD, with the potential for future
      therapeutic targets.

PMID- 24129594
TI  - Glucagon-like peptide-1 receptor-atrial natriuretic peptide axis: a novel
      mechanism for blood pressure regulation.

PMID- 24129595
TI  - Implementation of the power to prevent diabetes prevention educational curriculum
      into rural African American communities: a feasibility study.
AB  - PURPOSE: The purpose of this study was to describe the feasibility of using a
      community-based participatory research (CBPR) approach to implement the Power to
      Prevent (P2P) diabetes prevention education curriculum in rural African American
      (AA) settings. METHODS: Trained community health workers facilitated the 12
      session P2P curriculum across 3 community settings. Quantitative (based on the
      pre- and post-curriculum questionnaires and changes in blood glucose, blood
      pressure [BP], and weight at baseline and 6 months) and qualitative data (based
      on semi-structured interviews with facilitators) were collected. Indicators of
      feasibility included: demand, acceptability, implementation fidelity, and limited
      efficacy testing. RESULTS: Across 3 counties, 104 AA participants were recruited;
      43% completed >= 75% of the sessions. There was great demand for the program.
      Fifteen community health ambassadors (CHAs) were trained, and 4 served as
      curriculum facilitators. Content and structure of the intervention was acceptable
      to facilitators but there were challenges to implementing the program as
      designed. Improvements were seen in diabetes knowledge and the impact of healthy
      eating and physical activity on diabetes prevention, but there were no
      significant changes in blood glucose, BP, or weight. CONCLUSION: While it is
      feasible to use a CBPR approach to recruit participants and implement the P2P
      curriculum in AA community settings, there are significant challenges that must
      be overcome.

PMID- 24129596
TI  - Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending
      serotonergic modulation in inflammatory pain induced in formalin and carrageenan
      rat models.
AB  - BACKGROUND: Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are
      differentially involved in facilitatory or inhibitory descending modulation,
      respectively. Electrophysiological studies of the spinal cord have demonstrated
      that 5-HT3R is involved in nociception induced by intraplantar injection of
      formalin, but not carrageenan. In addition, depletion of spinal serotonin has
      been shown to attenuate pain behaviour in the formalin test, but there have been
      no such reports regarding the carrageenan model. This study compared the role of
      5-HT7R and the influence of descending serotonergic modulation between formalin-
      and carrageenan-induced inflammatory pain. METHODS: Effects of intrathecal (i.t.)
      AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in
      the formalin test and mechanical allodynia in the carrageenan model were
      evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t.
      5,7-dihydroxytryptamine was also examined in the two models. RESULTS: Intrathecal
      AS-19 significantly reduced the flinching responses in the formalin test
      (P<0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor
      SB269970 produced a significant change in mechanical allodynia in the carrageenan
      model. Depletion of spinal serotonin attenuated the flinching response in phase 2
      of the formalin test (P<0.01), but increased mechanical allodynia in the
      carrageenan model compared with controls (P<0.01). CONCLUSIONS: Spinal 5-HT7R
      plays a significant inhibitory role in descending serotonergic modulation in pain
      induced by formalin but not carrageenan. Descending serotonergic modulation is
      differentially involved in inflammatory pain induced by formalin and carrageenan,
      with facilitatory and inhibitory effects, respectively.

PMID- 24129597
TI  - Effect of palonosetron on the QTc interval in patients undergoing sevoflurane
      anaesthesia.
AB  - BACKGROUND: Palonosetron is a recently introduced 5-HT3 receptor antagonist for
      postoperative nausea and vomiting. Detailed standardized evaluation of corrected
      QT (QTc) interval change by palonosetron under sevoflurane anaesthesia is
      lacking. We evaluated QTc intervals in patients who are undergoing surgery with
      sevoflurane anaesthesia and receive palonosetron. METHODS: Our study included 100
      patients who were undergoing elective surgery under sevoflurane anaesthesia. The
      patients were randomly assigned to two groups: those who received an i.v.
      injection of palonosetron 0.075 mg immediately before induction of anaesthesia
      (pre-surgery group, n=50) and those who received it after surgery in the recovery
      room (post-surgery group, n=50). QTc intervals were measured before operation,
      intraoperatively (baseline, immediately after tracheal intubation, and at 2, 10,
      15, 30, 60, and 90 min after administration of palonosetron or placebo), and
      after operation (before and at 3, and 10 min after administration of palonosetron
      or placebo). QTc intervals were calculated using Fridericia's, Bazett's, or
      Hodges formulas. RESULTS: The perioperative QTc intervals were significantly
      increased from the baseline values, but were not affected by the pre- or post
      surgical timing of palonosetron administration. CONCLUSIONS: There was no
      significant difference in the QTc intervals during the perioperative period,
      whether 0.075 mg of palonosetron is administered before or after sevoflurane
      anaesthesia. Palonosetron may be safe in terms of QTc intervals during
      sevoflurane anaesthesia. Clinical trial registration ClinicalTrials.gov:
      NCT01650961.

PMID- 24129598
TI  - Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin.
AB  - 4-Hydroxycoumarin (4HC) type anticoagulants (for example, warfarin) are known to
      have a significant role in the treatment of thromboembolic diseases--a leading
      cause of patient morbidity and mortality worldwide. 4HC serves as an immediate
      precursor of these synthetic anticoagulants. Although 4HC was initially
      identified as a naturally occurring product, its biosynthesis has not been fully
      elucidated. Here we present the design, validation, in vitro diagnosis and
      optimization of an artificial biosynthetic mechanism leading to the microbial
      biosynthesis of 4HC. Remarkably, function-based enzyme bioprospecting leads to
      the identification of a characteristic FabH-like quinolone synthase from
      Pseudomonas aeruginosa with high efficiency on the 4HC-forming reaction, which
      promotes the high-level de novo biosynthesis of 4HC in Escherichia coli (~500 mg
      l-1 in shake flasks) and further in situ semisynthesis of warfarin. This work has
      the potential to be scaled-up for microbial production of 4HC and opens up the
      possibility of biosynthesizing diverse coumarin molecules with pharmaceutical
      importance.

PMID- 24129599
TI  - Correlating cation ordering and voltage fade in a lithium-manganese-rich lithium
      ion battery cathode oxide: a joint magnetic susceptibility and TEM study.
AB  - Structure-electrochemical property correlation is presented for lithium-manganese
      rich layered-layered nickel manganese cobalt oxide (LMR-NMC) having composition
      Li1.2Co0.1Mn0.55Ni0.15O2 (TODA HE5050) in order to examine the possible reasons
      for voltage fade during short-to-mid-term electrochemical cycling. The
      Li1.2Co0.1Mn0.55Ni0.15O2 based cathodes were cycled at two different upper cutoff
      voltages (UCV), 4.2 V and 4.8 V, for 1, 10, and 125 cycles; voltage fade was
      observed after 10 and 125 cycles only when the UCV was 4.8 V. Magnetic
      susceptibility and selected-area electron diffraction data showed the presence of
      cation ordering in the pristine material, which remained after 125 cycles when
      the UCV was 4.2 V. When cycled at 4.8 V, the magnetic susceptibility results
      showed the suppression of cation ordering after one cycle; the cation ordering
      diminished upon further cycling and was not observed after 125 cycles. Selected
      area electron diffraction data from oxides oriented towards the [0001] zone axis
      revealed a decrease in the intensity of cation-ordering reflections after one
      cycle and an introduction of spinel-type reflections after 10 cycles at 4.8 V;
      after 125 cycles, only the spinel-type reflections and the fundamental O3 layered
      oxide reflections were observed. A significant decrease in the effective magnetic
      moment of the compound after one cycle at 4.8 V indicated the presence of lithium
      and/or oxygen vacancies; analysis showed a reduction of Mn(4+) (high spin/low
      spin) in the pristine oxide to Mn(3+) (low spin) after one cycle. The effective
      magnetic moment was higher after 10 and 125 cycles at 4.8 V, suggesting the
      presence of Mn(3+) in a high spin state, which is believed to originate from
      distorted spinel (Li2Mn2O4) and/or spinel (LiMn2O4) compounds. The increase in
      effective magnetic moments was not observed when the oxide was cycled at 4.2 V,
      indicating the stability of the structure under these conditions. This study
      shows that structural rearrangements in the LMR-NMC oxide happen only at higher
      potentials (4.8 V, for example) and provides evidence of a direct correlation
      between cation ordering and voltage fade. 

PMID- 24129601
TI  - Tempranillo-derived grape seed extract induces apoptotic cell death and cell
      growth arrest in human promyelocytic leukemia HL-60 cells.
AB  - Although grape seed extract (GSE) has proven to be effective against various
      cancers, few studies have investigated the effects of GSE on human leukemia. In
      this study, we analysed the mechanisms involved in the apoptotic effects induced
      by GSE on human promyelocytic leukemia HL-60 cells. Thus, GSE treatment succeeded
      in activating caspase-3 (P < 0.05), the activation being dose-dependent and time
      dependent. Activation of caspase-3 induced by GSE was accompanied by
      mitochondrial membrane depolarization (P < 0.05). Moreover, disruption of
      mitochondrial integrity caused by GSE treatment subsequently led to activation of
      caspase-9 (P < 0.05), and also produced a slight increase in ROS levels (P <
      0.05). Cytotoxic effects elicited by GSE treatment ultimately resulted in
      extensive S-phase arrest (P < 0.05) and a substantial increase in the intrinsic
      rate of apoptosis (P < 0.05). Our findings suggest that the GSE induces apoptotic
      cell death and cell growth inhibition in human leukemic HL-60 cells, which seems
      to be dependent on mitochondrial damage. Therefore, the GSE obtained from
      Tempranillo cultivars could be an effective approach to restrain uncontrolled
      cell proliferation and survival in leukemia cells.

PMID- 24129602
TI  - High open circuit voltage organic photovoltaic cells fabricated using 9,9'
      bifluorenylidene as a non-fullerene type electron acceptor.
AB  - We have found that 9,9'BF can be used as an electron acceptor for P3HT-based OPVs
      while similar devices using 4,4'BP do not show any photovoltaic effect. This can
      be related to the respective aromaticity and antiaromaticity of the reduced forms
      of 9,9'BF or 4,4'BP. The OPV device fabricated using P3HT and 9,9'BF exhibited a
      PCE of 2.28% with a V(oc) of 1.07 V, a J(sc) of 5.04 mA cm(-2), and a FF of 0.42.

PMID- 24129600
TI  - Structural basis for a class of nanomolar influenza A neuraminidase inhibitors.
AB  - The influenza virus neuraminidase (NA) is essential for the virus life cycle. The
      rise of resistance mutations against current antiviral therapies has increased
      the need for the development of novel inhibitors. Recent efforts have targeted a
      cavity adjacent to the catalytic site (the 150-cavity) in addition to the primary
      catalytic subsite in order to increase specificity and reduce the likelihood of
      resistance. This study details structural and in vitro analyses of a class of
      inhibitors that bind uniquely in both subsites. Crystal structures of three
      inhibitors show occupation of the 150-cavity in two distinct and novel binding
      modes. We believe these are the first nanomolar inhibitors of NA to be
      characterized in this way. Furthermore, we show that one inhibitor, binding
      within the catalytic site, offers reduced susceptibility to known resistance
      mutations via increased flexibility of a pendant pentyloxy group and the ability
      to pivot about a strong hydrogen-bonding network. 

PMID- 24129603
TI  - Formative assessments in medical education: a medical graduate's perspective.

PMID- 24129604
TI  - Auditory forebrain neurons track temporal features of time-warped natural
      stimuli.
AB  - A fundamental challenge for sensory systems is to recognize natural stimuli
      despite stimulus variations. A compelling example occurs in speech, where the
      auditory system can recognize words spoken at a wide range of speeds. To date,
      there have been more computational models for time-warp invariance than
      experimental studies that investigate responses to time-warped stimuli at the
      neural level. Here, we address this problem in the model system of zebra finches
      anesthetized with urethane. In behavioral experiments, we found high
      discrimination accuracy well beyond the observed natural range of song
      variations. We artificially sped up or slowed down songs (preserving pitch) and
      recorded auditory responses from neurons in field L, the avian primary auditory
      cortex homolog. We found that field L neurons responded robustly to time-warped
      songs, tracking the temporal features of the stimuli over a broad range of warp
      factors. Time-warp invariance was not observed per se, but there was sufficient
      information in the neural responses to reliably classify which of two songs was
      presented. Furthermore, the average spike rate was close to constant over the
      range of time warps, contrary to recent modeling predictions. We discuss how this
      response pattern is surprising given current computational models of time-warp
      invariance and how such a response could be decoded downstream to achieve time
      warp-invariant recognition of sounds.

PMID- 24129605
TI  - Coadaptation and conflict, misconception and muddle, in the evolution of genomic
      imprinting.
AB  - Common misconceptions of the 'parental conflict' theory of genomic imprinting are
      addressed. Contrary to widespread belief, the theory defines conditions for
      cooperation as well as conflict in mother-offspring relations. Moreover, conflict
      between genes of maternal and paternal origin is not the same as conflict between
      mothers and fathers. In theory, imprinting can evolve either because genes of
      maternal and paternal origin have divergent interests or because offspring
      benefit from a phenotypic match, or mismatch, to one or other parent. The latter
      class of models usually require maintenance of polymorphism at imprinted loci for
      the maintenance of imprinted expression. The conflict hypothesis does not require
      maintenance of polymorphism and is therefore a more plausible explanation of
      evolutionarily conserved imprinting. 

PMID- 24129606
TI  - The genetic basis and experimental evolution of inbreeding depression in
      Caenorhabditis elegans.
AB  - Determining the genetic basis of inbreeding depression is important for
      understanding the role of selection in the evolution of mixed breeding systems.
      Here, we investigate how androdioecy (a breeding system characterized by partial
      selfing and outcrossing) and dioecy (characterized by obligatory outcrossing)
      influence the experimental evolution of inbreeding depression in Caenorhabditis
      elegans. We derived inbred lines from ancestral and evolved populations and found
      that the dioecious lineages underwent more extinction than androdioecious
      lineages. For both breeding systems, however, there was selection during
      inbreeding because the diversity patterns of 337 single-nucleotide polymorphisms
      (SNPs) among surviving inbred lines deviated from neutral expectations. In
      parallel, we also followed the evolution of embryo to adult viability, which
      revealed similar starting levels of inbreeding depression in both breeding
      systems, but also outbreeding depression. Under androdioecy, diversity at a
      neutral subset of 134 SNPs correlated well with the viability trajectories,
      showing that the population genetic structure imposed by partial selfing affected
      the opportunity for different forms of selection. Our findings suggest that the
      interplay between the disruptions of coevolved sets of loci by outcrossing, the
      efficient purging of deleterious recessive alleles with selfing and overdominant
      selection with outcrossing can help explain mixed breeding systems. 

PMID- 24129607
TI  - Bioinformatic analysis of the four transcription factors used to induce
      pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells are a type of pluripotent stem cell
      artificially derived from non-pluripotent cells by overexpressing the
      transcription factors Oct4, Sox2, Klf4 and Nanog. These transcription factors
      play a pivotal role in stem cells; however, the function of these factors are not
      fully characterized. In this study, we analyzed Oct4, Sox2, Klf4 and Nanog in ten
      different species using bioinformatics, to provide more knowledge of the function
      of these genes. Nanog does not exist in the invertebrates Caenorhabditis elegans
      and Drosophila melanogaster, indicating that the absence of Nanog may be
      responsible for the developmental differences between vertebrates and
      invertebrates. Construction of phylogenetic trees confirmed that the function of
      Nanog is conserved from fish to mammals. The effect of alternative splicing on
      the protein domains present in Oct4, Sox2, Klf4 and Nanog were also analyzed.
      Examination of the expression patterns in human stem cells, iPS cells and normal
      tissues showed that Oct4, Sox2, Klf4 and Nanog are expressed at similar levels in
      iPS cells and embryonic stem cells, and expression of all four transcription
      factors decreases after differentiation. Expression of Klf4 reduced to the least
      during differentiation, and Klf4 was found to be specifically expressed in
      several normal tissues, especially the salivary gland. In this paper, we
      systematically indentified the family proteins of the four transcription factors
      used to induce pluripotent stem cells, and then analyzed their evolution status,
      composed of those protein domains, alternative splicing translation, expression
      status and interaction networks. Those analysis could shed a light for further
      research of iPS. 

PMID- 24129608
TI  - Does economic environment influence the strength of the positive association
      between suicide and unemployment?

PMID- 24129609
TI  - Informing the 'early years' agenda in Scotland: understanding infant feeding
      patterns using linked datasets.
AB  - BACKGROUND: Providing infants with the 'best possible start in life' is a
      priority for the Scottish Government. This is reflected in policy and health
      promotion strategies to increase breast feeding, which gives the best source of
      nutrients for healthy infant growth and development. However, the rate of breast
      feeding in Scotland remains one of the lowest in Europe. Information is needed to
      provide a better understanding of infant feeding and its impact on child health.
      This paper describes the development of a unique population-wide resource created
      to explore infant feeding and child health in Scotland. METHODS: Descriptive and
      multivariate analyses of linked routine/administrative maternal and infant health
      records for 731,595 infants born in Scotland between 1997 and 2009. RESULTS: A
      linked dataset was created containing a wide range of background, parental,
      maternal, birth and health service characteristics for a representative sample of
      infants born in Scotland over the study period. There was high coverage and
      completeness of infant feeding and other demographic, maternal and infant
      records. The results confirmed the importance of an enabling environment-
      cultural, family, health service and other maternal and infant health-related
      factors--in increasing the likelihood to breast feed. CONCLUSIONS: Using the
      linked dataset, it was possible to investigate the determinants of breast feeding
      for a representative sample of Scottish infants born between 1997 and 2009. The
      linked dataset is an important resource that has potential uses in research,
      policy design and targeting intervention programmes.

PMID- 24129610
TI  - The role of a personalized dietary intervention in managing gestational weight
      gain: a prospective, controlled study in a low-risk antenatal population.
AB  - PURPOSE: To compare the efficacy of a personal dietary intervention on
      gestational weight gain control with a general intervention promoting healthy
      eating. METHODS: Prospective, controlled study including 154 low-risk pregnant
      women randomly allocated to two groups: 77 receiving a personalized diet plan and
      a close follow-up by a dietician (intervention group), 77 receiving standard
      dietary care by means of a brochure on healthy eating during pregnancy (control
      group). Pre-pregnancy weight, gestational age, height, weight and BMI at
      baseline, weight at term, gestational age at delivery and newborn weight were
      recorded for all participants. The primary end-point was the difference in body
      weight between baseline and term. Secondary end-points were the difference in
      body weight between pre-pregnancy and term and in newborn weights. RESULTS:
      Maternal weight gain at term was significantly lower both as compared to pre
      pregnancy weight (8.2 +/- 4.0 vs. 13.4 +/- 4.2 kg; p < 0.001) and to weight at
      baseline (7.7 +/- 3.8 vs. 13.7 +/- 4.3 kg; p < 0.001) in the intervention group
      as compared to controls. A positive, significant correlation between the delta
      weight between baseline and term and newborn weight was observed in both groups,
      but stronger in patients from the intervention group (intervention group R =
      0.76, p < 0.001; control group R = 0.35, p = 0.01). CONCLUSIONS: This study
      suggests that a personalized nutritional intervention, in which the dietician
      plays an active role within the obstetric team, may represent a successful
      approach in limiting weight gain in pregnant women.

PMID- 24129611
TI  - Body mass index in relation to semen quality and reproductive hormones in New
      Zealand men: a cross-sectional study in fertility clinics.
AB  - STUDY QUESTION: Is there an association between body mass index (BMI) and routine
      semen analysis parameters in adult men? SUMMARY ANSWER: No significant
      correlation was found between BMI and semen parameters measured with the
      exception of normal sperm morphology. WHAT IS KNOWN ALREADY: Multiple cross
      sectional studies have found inconsistent results, with two meta-analyses finding
      no correlation between BMI and semen parameters. A relationship between BMI and
      male reproductive hormones, particularly total testosterone, has been established
      in several studies and a systematic review. STUDY DESIGN, SIZE, DURATION: Cross
      sectional study of 511 men recruited at the time of semen analysis over 4 years
      (2008-2012). PARTICIPANTS/MATERIALS, SETTING, METHODS: Men presenting for semen
      analysis for any reason at participating fertility clinics in Auckland, New
      Zealand were recruited, with BMI measured or self-reported at this time.
      Exclusion criteria included azoospermia and pathological conditions of male
      genital tract. Conventional BMI categories were used (underweight <18.5 kg/m(2),
      normal 18.5-24.99 kg/m(2), overweight 25.00-29.99 kg/m(2), obese >=30 kg/m(2)).
      The routine semen analysis results for sperm concentration, total sperm count,
      sperm motility (total motility), sperm morphology, semen volume and total motile
      sperm (primary outcome) from one semen sample were recorded. Consent from 175 men
      was obtained to measure LH, FSH, estradiol, total testosterone, free testosterone
      and sex hormone-binding globulin (SHBG) in a blood sample (secondary outcome).
      Associations between BMI and these outcomes were assessed using Spearman
      correlation and analysis of variance, and a multiple linear regression analysis
      was performed. In addition, the relative risks for men having abnormal semen
      analysis results according to reference ranges of the World Health Organization,
      such as oligozoospermia, were calculated. This study has sufficient power to
      detect a doubling in abnormally low sperm concentration and total sperm count in
      overweight or obese men compared with men with normal BMI. Participation rate was
      not recorded. MAIN RESULTS AND THE ROLE OF CHANCE: The body mass indices from
      measured and self-reported samples had an equivalent range of values which did
      not differ statistically. Median BMI was 27.1 kg/m(2) [10th-90th percentile: 22.8
      32.9]. Overall, 72.8% of the study population were overweight or obese (BMI >25
      kg/m(2)), while 19 men (3.72%) had a BMI of 35-40 kg/m(2) and 7 men (1%) had a
      BMI of >40 kg/m(2). No significant correlation was found between BMI and the
      semen parameters measured with the exception of normal sperm morphology (r =
      0.12, P = 0.024), although this finding is derived from only 330 samples.
      Overweight and obese men showed no significantly increased relative risk of
      abnormal semen parameters. Of the reproductive hormones, significant negative
      relationships with BMI were found for total testosterone (r = -0.35, P =
      <0.0001), free testosterone (r = -0.25, P = <0.0012) and SHBG (r = -0.44, P =
      <0.0001). Multiple linear regression analysis also showed that BMI had a
      marginally significant effect on normal sperm morphology (effect estimate =0.47,
      P = 0.038). In addition, <2 days of abstinence was negatively associated with
      semen volume (effect estimate =-0.80, P = 0.0074) and summer season was
      negatively associated with sperm concentration (effect estimate =-14.9, P =
      0.020). LIMITATIONS, REASONS FOR CAUTION: The power of this study is limited by
      the relatively small overall sample size, although it does have one of the
      largest proportions of obese men (23.3%) in published cross-sectional studies.
      The study involved samples from men attending a fertility clinic, who are likely
      to have a lower semen quality and higher rate of pathology compared with the
      general population, therefore limiting the possible generalization of this study
      to all adult men. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent
      with those of other cross-sectional studies as well as two meta-analyses but do
      disagree in part with the most recent meta-analysis (which found significant odds
      ratios for oligozoospermia and azoospermia with increased BMI) and with studies
      measuring DNA fragmentation index. Therefore a definitive conclusion on the
      effect of BMI on semen quality remains uncertain while our data reinforce
      previous findings that BMI is negatively associated with male reproductive
      hormones. STUDY FUNDING/COMPETING INTEREST(S): All funding for this study was
      from New Zealand academic and charitable sources including: Faculty of Medical
      and Health Sciences, University of Auckland (New Zealand), the Mercia Barnes
      Trust of the Royal Australian and New Zealand College of Obstetricians and
      Gynaecologists and the Nurture Foundation for Reproductive Research. The authors
      have no conflicts of interest to declare.

PMID- 24129612
TI  - Are children born after assisted reproductive technology at increased risk of
      autism spectrum disorders? A systematic review.
AB  - STUDY QUESTION: Are children born after assisted reproductive technology (ART) at
      increased risk of autism spectrum disorders (ASD)? SUMMARY ANSWER: There is no
      evidence that ART significantly increases the risk of ASD in the offspring. WHAT
      IS KNOWN ALREADY: A few systematic reviews have explored the correlation between
      assisted conception and ASD with inconclusive results, partly due to the
      heterogeneity of diagnostic criteria and methodology in the different studies.
      STUDY DESIGN, SIZE, DURATION: Systematic review of 7 observational studies (2
      cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD
      published since 2000. MATERIALS, SETTING, METHODS: Literature searches were
      conducted to retrieve observational studies on the risk of ASD in ART population.
      Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more
      consistent results, we only included the studies in which (i) subjects with
      either infantile autism or ASD could be identified according to international
      classification systems and (ii) the diagnosis was obtained from hospital records.
      Seven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF
      CHANCE: Four out of seven studies, including the two with the best quality
      scores, did not show an association between ART and ASD. The two papers
      supporting an increased risk of autism following ART had the lowest quality
      scores, due to major methodological limitations. Only one paper showed a
      protective role of ART. LIMITATIONS, REASONS FOR CAUTION: In spite of the strict
      inclusion criteria applied as to the diagnosis of ASD, the papers selected are
      heterogeneous in many aspects including study design, definitions of ART, data
      source and analysed confounders. WIDER IMPLICATIONS OF THE FINDINGS: At present,
      there is no evidence that ART is significantly associated with ASD and hence that
      current health policies should be modified. The divergent results of some of the
      studies suggest that further prospective, large and high-quality studies are
      still needed. STUDY FUNDING/COMPETING INTEREST(S): This work was supported, in
      part, by the Italian Ministry of Health and by Tuscany Region. The authors have
      no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

PMID- 24129613
TI  - Comparison of early versus late initiation of GnRH antagonist co-treatment for
      controlled ovarian stimulation in IVF: a randomized controlled trial.
AB  - STUDY QUESTION: What is the impact of initiating GnRH antagonist co-treatment for
      in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth
      rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)?
      SUMMARY ANSWER: Early initiation of GnRH antagonist does not appear to improve
      clinical outcomes of IVF compared with midfollicular initiation. WHAT IS KNOWN
      ALREADY: During ovarian stimulation for IVF, GnRH antagonist co-treatment is
      usually administered from the midfollicular phase onwards. Earlier initiation may
      improve the follicular phase hormonal milieu and therefore overall clinical
      outcomes. STUDY DESIGN, SIZE, DURATION: This open-label, multicentre randomized
      controlled trial was conducted between September 2009 and July 2011. A web-based
      program was used for randomization and 617 IVF-intracytoplasmic sperm injection
      (ICSI) patients were included. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Recombinant FSH (150-225 IU) was administered daily from CD 2 onwards in both
      groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD
      2, whereas the control group (CD6; n = 309) started on CD 6. MAIN RESULTS AND THE
      ROLE OF CHANCE: There were no significant differences in clinical outcomes
      between the two groups. A non-significant trend towards a higher LBR per started
      cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR:
      24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6). LIMITATIONS,
      REASONS FOR CAUTION: The study was terminated prematurely because no significant
      difference was observed in clinical outcomes after 617 inclusions. A much larger
      study population would be needed to detect a small significant difference in
      favour of either study arm, which raises the question of whether this would be
      relevant for clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: The present
      study shows that the additional treatment burden and costs of starting GnRH
      antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of
      GnRH antagonist does not improve LBRs. STUDY FUNDING/COMPETING INTEREST(S): This
      study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V.,
      P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have
      nothing to declare. F.J.B. has received fees and grant support from the following
      companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and
      Roche. B.J.C. has received fees and grant support from the following companies
      (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and
      grant support from the following companies (in alphabetic order): Auxogen,
      Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support
      from the following companies (in alphabetic order): Andromed, Ardana, Ferring,
      Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering,
      Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support
      from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck
      Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant
      support from the following companies (in alphabetic order): Anecova, Ferring,
      Merck Serono, MSD, Organon and Serono. TRIAL REGISTRATION NUMBER:
      www.clinicaltrials.gov, no. NCT00866034.

PMID- 24129614
TI  - Long-term effects of prenatal exposure to perfluoroalkyl substances on female
      reproduction.
AB  - STUDY QUESTION: Does prenatal exposure to perfluoroalkyl substances (PFASs) have
      long-term effects on female reproductive function?. SUMMARY ANSWER: Our results
      suggest an association between in utero exposure to perfluorooctanoic acid (PFOA)
      and delay in age of menarche. WHAT IS KNOWN ALREADY: Previous cross-sectional
      studies have reported possible effects of PFASs on female reproduction including
      reduced fecundity, delayed puberty and accelerated age at menopause. Only limited
      data exist from follow-up studies on long-term implications of prenatal exposure
      to PFASs. STUDY DESIGN, SIZE, DURATION: In this study we used data from a Danish
      population-based cohort established in 1988-1989. Of 1212 eligible pregnant
      women, 965 participated. Follow-up was initiated in 2008 on the female offspring
      at ~20 years of age. Three hundred and sixty seven (84%) daughters answered a
      questionnaire and 267 (61%) daughters furthermore attended clinical examinations
      which were conducted in 2008-2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      final study population consisted of 343 daughters of which 254 had attended the
      clinical examinations and 89 had answered the questionnaire only. Levels of PFASs
      in maternal serum from pregnancy week 30 were used as a measure of prenatal
      exposure and related to age of menarche, menstrual cycle length, levels of
      reproductive hormones and follicle number of the daughters. Data were divided
      into three groups according to tertiles of maternal concentrations of PFASs (low,
      medium, high). MAIN RESULTS AND THE ROLE OF CHANCE: In adjusted regression
      analyses, daughters exposed to higher levels of PFOA in utero had a 5.3 (95%
      confidence interval: 1.3; 9.3) months later age of menarche compared with the
      reference group of lower PFOA. Crude (P = 0.05) and adjusted (P = 0.01) trend
      tests also indicated a relationship between higher prenatal PFOA exposure and
      delay of menarche. LIMITATIONS, REASONS FOR CAUTION: We did not measure the exact
      amount of PFASs to which the daughters had been exposed prenatally. Instead we
      used PFAS concentrations in maternal serum as surrogates. However, PFASs are
      efficiently transferred to the fetus via placenta. Information on age of menarche
      was collected retrospectively but the time interval for recall in our study was
      relatively short (2-10 years). The remaining outcome measures depended on
      participation in clinical examination which reduced the number of observations
      leading to limited statistical power and risk of selection bias. WIDER
      IMPLICATIONS OF THE FINDINGS: Since PFASs can be detected in humans all over the
      world, effects of prenatal exposure on female reproductive function later in life
      may have wide health implications. STUDY FUNDING/COMPETING INTEREST(S): The study
      was supported by the Danish Council for Independent Research (271-05-0296, 09
      065631), the Danish Ministry of Interior and Health (0-302-02-18/5), the Danish
      Council for Strategic Research (09-067124 (Centre for Fetal Programming), 09
      063072, 2101-06-0005), the Novo Nordisk Foundation, the Aarhus University
      Research Foundation, the Frimodt-Heineke Foundation, the Foundation of Maria
      Dorthea and Holger From, the Beckett-Foundation, the Research Grant of Organon
      and the Foundation of Lily Benthine Lund. There are no competing interests. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 24129615
TI  - Mechanistic foundations of the metaphase II spindle of human oocytes matured in
      vivo and in vitro.
AB  - STUDY QUESTION: Are morphometric and morphological parameters of the metaphase II
      (MII) spindle of human oocytes matured in vivo or in vitro predictive of
      chromosome alignment on the metaphase plate? SUMMARY ANSWER: Morphometric spindle
      parameters were very comparable between oocytes matured in vivo and in vitro and
      were unable to predict chromosome alignment, while a flattened shape of both
      poles was positively associated with chromosome displacement from the metaphase
      plate. WHAT IS KNOWN ALREADY: The relationship between MII spindle morphometry
      and chromosome alignment has only been sporadically investigated in human
      oocytes. The possible implications of spindle pole morphology are totally
      unrecognized. STUDY DESIGN, SIZE, DURATION: Morphometric and morphological
      analysis of the MII spindle of donated supernumerary human oocytes (N = 93) aimed
      at investigating possible associations between novel microtubule parameters and
      chromosome arrangement. PARTICIPANTS/MATERIALS, SETTING, METHODS: MII oocytes
      from three sources were analysed: (i) stimulated cycles matured in vivo (ivo
      MII), (ii) leftover cumulus-free germinal vesicle oocytes from stimulated cycles
      matured in vitro (lgv-MII) and (iii) immature cumulus-cell oocyte complexes
      (COCs) recovered from in vitro maturation (IVM) cycles and matured in vitro (ivm
      MII). Oocytes were fixed and stained for tubulin, chromatin and actin. Optical
      sections were collected at 0.3 um intervals by high-performance confocal
      microscopy and three-dimensionally reconstructed for assignment of specific
      spindle and chromosomal properties. Spindle pole morphology was classified as
      either focused or flattened depending on whether microtubule ends were more or
      less convergent, respectively. Optical density measurements were generated to
      estimate microtubule abundance in chromosome to pole domains proximal and distal
      to the oolemma. MAIN RESULTS AND THE ROLE OF CHANCE: In ivo-MII oocytes, the
      sizes (mean +/- SD) of major and minor axes were 11.8 +/- 2.6 and 8.9 +/- 1.7
      MUm, respectively, while maximum projection was 88.8 +/- 29.5 MUm(2). Very
      comparable values of these parameters were found in lgv-MII and ivm-MII oocytes.
      Double-focused spindles were rarely found (3.1%), unlike those with a double
      flattened conformation (47.7%). Spindles with both focused and flattened poles
      amounted to almost half of the sample set (49.2%), but in this subgroup it was
      very infrequent (4.6%) to observe the flattened pole oriented towards the
      oolemma. Overall, differences in the relative proportions of pole morphology
      categories in ivo-MII, lgv-MII and ivm-MII oocytes were not statistically
      significant. For both the distal and proximal spindle hemidomains, optical
      intensity profiles were also comparable between ivo-MII, lgv-MII and ivm-MII
      oocytes. None of the morphometric parameters (major and minor axes, their ratio,
      maximum projection, distances of the metaphase plate from the poles) was
      associated with chromosome alignment on the metaphase plate or arrangement inside
      and outside the spindle. Importantly, a double-flattened outline of pole
      morphology was positively associated with the displacement of one or more
      chromosomes from the metaphase plate. Moreover, when a flattened pole was
      oriented towards the oolemma, a higher rate of chromosome displacement was
      observed. LIMITATIONS, REASONS FOR CAUTION: The findings of the study will
      require confirmation by further in-depth analysis and extension of the database,
      especially regarding the relationship between microtubule abundance and
      chromosome arrangement. Furthermore, considering the high number of comparisons,
      the observed statistical differences will require future 'ad hoc' analysis. WIDER
      IMPLICATIONS OF THE FINDINGS: Collectively, this work provides a robust database
      for future research on the human oocyte cytoskeleton, and contributes to a better
      definition of oocyte quality in assisted reproduction technology. Also, these
      data support the notion that IVM does not affect spindle morphometry and
      morphology. STUDY FUNDING/COMPETING INTEREST(S): Part of this work was supported
      by a grant awarded by the Italian Ministry of Labour, Health and Social Policies.
      The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER:
      Not applicable.

PMID- 24129616
TI  - Antidepressants for neuro-regeneration: from depression to Alzheimer's disease.
AB  - Recently identified new potential functions of antidepressants in the treatment
      of neurodegenerative will be introduced. Antidepressants are reported to regulate
      stem cell fate to regenerate neurons in the adult hippocampus and are effective
      in reducing toxic amyloid peptides and are known to increase neurotrophic factor
      such as brain-derived neurotrophic factor. Clinical trial data support that
      antidepressants have potential to treat Alzheimer's disease. 

PMID- 24129617
TI  - Novel 2,4-dianilino-5-fluoropyrimidine derivatives possessing ALK inhibitory
      activities.
AB  - A new series of 2,4-dianilino-5-fluoropyrimidine derivatives were designed and
      synthesized and their anaplastic lymphoma kinase (ALK) inhibitory activities were
      evaluated by biochemical and cell-based assays in order to discover a new ALK
      inhibitor. Most compounds synthesized showed good inhibitory activities against
      ALK and good cytotoxic activities in H3122 cell line. The best compound 6f showed
      good activity against wild-type ALK along with crizotinib-resistant mutant ALK,
      and it showed 6 times better activity in cell-based assay than crizotinib. Some
      SAR studies were performed by the comparisons of the activities between 6 and the
      designed-synthesized compounds. 

PMID- 24129618
TI  - AlCl3-promoted [3 + 2] annulation of cis-2,3-disubstituted cyclopropane 1,1
      diesters with isothiocyanates: stereoselective synthesis of densely substituted 2
      iminodihydrothiophenes.
AB  - cis-2,3-Disubstituted cyclopropane 1,1-diesters were found to be much more
      reactive than their corresponding trans-isomers in the AlCl3-promoted [3 + 2]
      annulations with isothiocyanates. The reaction with the cis-cyclopropanes
      proceeded to completion within minutes, providing a variety of densely
      substituted diastereomerically pure 2-iminodihydrothiophenes in moderate to
      excellent yields. 

PMID- 24129619
TI  - Haloplanus salinus sp. nov., an extremely halophilic archaeon from a Chinese
      marine solar saltern.
AB  - Halophilic archaeal strain YGH66(T) was isolated from the Yinggehai marine solar
      saltern near the Sanya city of Hainan Province, China. Cells were pleomorphic,
      flat, stained Gram-negative, and produced pink-pigmented colonies. Strain
      YGH66(T) was able to grow at 20-50  degrees C (optimum 37  degrees C), at 0.9-4.8
      M NaCl (optimum 3.1 M NaCl), at 0.005-1.0 M MgCl2 (optimum 0.05 M MgCl2), and at
      pH 6.0-8.0 (optimum pH 7.0). The cells of strain YGH66(T) were lysed in distilled
      water, and the minimum NaCl concentration that prevented cell lysis was 5 %
      (w/v). The major polar lipids of the strain were phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate, one
      major glycolipid (GL1) chromatographically identical to sulfated mannosyl
      glucosyl diether and a minor unidentified lipid (GL2), respectively. On the basis
      of 16S rRNA gene sequence analysis, strain YGH66(T) was closely related to
      Haloplanus natans JCM 14081(T), Haloplanus aerogenes TBN37(T), and Haloplanus
      vescus RO5-8(T) with the similarities of 98.0, 97.6, and 96.9 %, respectively.
      The rpoB' gene similarity between strain YGH66(T) and the current three members
      of Haloplanus were 90.4-92.8 %. The DNA G+C content of strain YGH66(T) was 67.2
      mol %. The DNA-DNA hybridization values between strain YGH66(T) and three members
      of Haloplanus, H. natans JCM 14081(T), H. aerogenes TBN37(T), H. vescus RO5-8(T)
      were 50, 46 and 39 %, respectively. It was concluded that strain YGH66(T)
      represents a novel species of the genus Haloplanus, for which the name Haloplanus
      salinus sp. nov. is proposed. The type strain is YGH66(T) (=CGMCC 1.12127(T) =
      JCM 18368(T)). 

PMID- 24129620
TI  - First identification of Salmonella Urbana and Salmonella Ouakam in humans in
      Africa.
AB  - INTRODUCTION: Salmonella infections are increasing worldwide, but there are few
      reports on Salmonella surveillance in African countries and other developing
      countries. This has made it difficult to estimate the actual burden of
      salmonellosis, especially in Africa. This study was conducted in a neglected
      Northern Region of Ghana where there are no previous data on Salmonella
      serotypes. METHODOLOGY: Standard microbiological tests were used for isolation,
      identification, and serotyping. Micro-dilution was used for the antimicrobial
      susceptibility tests. RESULTS: Four serotypes of Salmonella were identified: S.
      Urbana, S. Ouakam, S. Senftenberg, and S. Stanleyville. All the serotypes were
      susceptible to the 20 antibiotics used in the susceptibility test. S. Urbana and
      S. Ouakam were identified in humans for the first time in Africa. CONCLUSION:
      This study may serve as a baseline study for future investigations on Salmonella
      in the region and may assist public health officials to take the appropriate
      measures in case of a disease outbreak caused by Salmonella in the area. The
      article may also give health officials a fair idea of the resistance level of
      these serotypes in the region.

PMID- 24129621
TI  - Genomics of an emerging clone of Salmonella serovar Typhimurium ST313 from
      Nigeria and the Democratic Republic of Congo.
AB  - INTRODUCTION: Salmonella enterica serovar Typhimurium ST313 is an invasive and
      phylogenetically distinct lineage present in sub-Saharan Africa. We report the
      presence of S. Typhimurium ST313 from patients in the Democratic Republic of
      Congo and Nigeria. METHODOLOGY: Eighteen S. Typhimurium ST313 isolates were
      characterized by antimicrobial susceptibility testing, pulsed-field gel
      electrophoresis (PFGE), and multilocus sequence typing (MLST). Additionally, six
      of the isolates were characterized by whole genome sequence typing (WGST). The
      presence of a putative virulence determinant was examined in 177 Salmonella
      isolates belonging to 57 different serovars. RESULTS: All S. Typhimurium ST313
      isolates harbored resistant genes encoded by blaTEM1b, catA1, strA/B, sul1, and
      dfrA1. Additionally, aac(6')1aa gene was detected. Phylogenetic analyses revealed
      close genetic relationships among Congolese and Nigerian isolates from both blood
      and stool. Comparative genomic analyses identified a putative virulence fragment
      (ST313-TD) unique to S. Typhimurium ST313 and S. Dublin. CONCLUSION: We showed in
      a limited number of isolates that S. Typhimurium ST313 is a prevalent sequence
      type causing gastrointestinal diseases and septicemia in patients from Nigeria
      and DRC. We found three distinct phylogenetic clusters based on the origin of
      isolation suggesting some spatial evolution. Comparative genomics showed an
      interesting putative virulence fragment (ST313-TD) unique to S. Typhimurium ST313
      and invasive S. Dublin.

PMID- 24129623
TI  - Infection due to colistin-resistant Enterobacteriacae in critically-ill patients.
AB  - INTRODUCTION: This study was conducted in response to the rising incidence of
      drug resistance observed in the intensive care unit (ICU) of King Fahad Medical
      City. METHODOLOGY: A retrospective observational study was conducted in the ICU
      of King Fahad Medical City between October 2003 and April 2012. Data were
      collected using a structured data sheet. RESULTS: Nine episodes of infection with
      colistin-resistant Enterobacteriacae were recorded in seven patients. Five were
      females with an average age of 59.75 years. All patients had multiple co
      morbidities; five had diabetes mellitus. In five of the episodes, Klebsiella
      pneumoniae was responsible, Serratia marcescens was reported in two, while
      Enterobacter aerogenes and Providencia stuartii were responsible for one episode
      of infection each. Prior colistin use was documented in all but one patient.
      Colistin resistance was defined by a minimum inhibitory concentration (MIC) of >
      4 ug/mL according to the European Committee on Antimicrobial Susceptibility
      Testing (EUCAST) clinical breakpoint for Enterobacteriacae. Various antibiotics
      were used to treat the patients, with mortality reported in two. CONCLUSION:
      Infection due to colistin-resistant Enterobacteriacae is a rising challenge in
      Saudi Arabia; colistin use is thought to be associated with these infections.
      This calls for a stricter antimicrobial stewardship program and improved
      infection control measures to curb the rising trend of antibiotic resistance.

PMID- 24129622
TI  - Increasing incidence of Gram-negative organisms in bacterial agents isolated from
      diabetic foot ulcers.
AB  - INTRODUCTION: In the present study, we sought to identify the bacterial organisms
      associated with diabetic foot infections (DFIs) and their antibiotic sensitivity
      profiles. METHODOLOGY: We retrospectively reviewed the records of wound cultures
      collected from diabetic patients with foot infections between May 2005 and July
      2010. RESULTS: We identified a total of 298 culture specimens (165 [55%] wound
      swab, 108 [36%] tissue samples, and 25 [9%] bone samples) from 107 patients (74
      [69%] males and 33 [31%] females, mean age 62 +/- 13 yr) with a DFI. Among all
      cultures 83.5% (223/267) were monomicrobial and 16.4% (44/267) were
      polymicrobial. Gram-negative bacterial isolates (n = 191; 61.3%) significantly
      outnumbered Gram-positive isolates (n = 121; 38.7%). The most frequently isolated
      bacteria were Pseudomonas species (29.8%), Staphylococcus aureus (16.7%),
      Enterococcus species (11.5%), Escherichia coli (7.1%), and Enterobacter species
      (7.1%), respectively. While 13.2% of the Gram-negative isolates were inducible
      beta-lactamase positive, 44.2% of Staphylococcus aureus isolates were methicillin
      resistant. CONCLUSIONS: Our results support the recent view that Gram-negative
      organisms, depending on the geographical location, may predominate in DFIs.

PMID- 24129624
TI  - Assessing therapeutic management of vaginal and urethral symptoms in an anonymous
      HIV testing centre in Luanda, Angola.
AB  - INTRODUCTION: This study aimed to estimate the prevalence of Neisseria
      gonorrhoeae and Chlamydia trachomatis infections and to assess the therapeutic
      management of vaginal/urethral discharge and dysuria in patients with human
      immunodeficiency virus in Luanda, Angola, taking into account World Health
      Organization recommendations for sexually transmitted infection syndromic
      management. METHODOLOGY: Socio-demographic and medical data were obtained from
      436 individuals, and clinical examinations were performed in 104 women and 8 men.
      Vaginal/cervical and urethral specimens were collected from 112 individuals for
      observation of Trichomonas vaginalis, yeasts and bacterial vaginosis, while urine
      samples were obtained from 415 patients (221 symptomatic and 194 asymptomatic).
      Diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis was performed by
      polymerase chain reaction assay. RESULTS: The prevalence of N. gonorrhoeae and C.
      trachomatis was 8.4% (35/415) and 7.9%, (33/415) respectively. Eight of the 35 N.
      gonorrhoeae positive cases were treated. All men and women (79) who presented a
      positive wet mount/Gram stain were etiologically treated according to microscopy
      results. In contrast, 53.3% of the female patients (16/30) and 33.3% (1/3) of the
      male patients who presented microscopy negative results were treated for urinary
      tract infection or by syndromic approach. Among non-examined patients, 15% of
      women (12/80) and 52.5% of men (21/40) were treated without an etiological
      result. Syndromic treatment was preferentially given to non-examined males (19/40
      47.5%) over females (12/80-15%) (p<0.01). CONCLUSIONS: The prevalence of N.
      gonorrehaea and C. trachomatis found in this study was high. WHO-recommended
      syndromic management of vaginal/urethral discharge is not being consistently and
      correctly applied.

PMID- 24129625
TI  - Ugandan medical and health sciences interns' infection control knowledge and
      practices.
AB  - BACKGROUND: We assessed the level of knowledge, attitudes, and practices of
      recent graduates of clinical health sciences who started their one-year
      internship in Uganda. METHODOLOGY: This was a cross-sectional survey responded to
      by 209 (response rate of 70%) new interns who started their internships in August
      2011 in different Ugandan hospitals. Validated self-administered questionnaires
      with knowledge, attitude, and practices questions were distributed to the
      participants during a two-day internship orientation organized by the national
      internship committee. RESULTS: Out of 299 subjects approached, the survey was
      completed and returned by 209 (70%). More nurses (51.4%) failed the questions on
      odds of HIV transmission after a needle stick injury compared to 23.0% and 36.4%
      of medical and dental graduates, respectively(chi2 = 24.06 p = 0.001). There was
      no difference in proportions of those who re-sheath needles. Respondents who had
      an encounter with positive tuberculosis history when taking clinical notes while
      unprotected were not more motivated to use masks (chi2 = 7.06; p = 0.07). Nurses
      and dentists reported more regular hand washing before and after patient contact
      compared to medical doctors. CONCLUSION: Overall, the knowledge of infection
      control was not impressive and the attitudes and practices appeared to be heavily
      influenced by the lack of an enabling environment in training hospitals and
      internship hospitals. There is little likelihood of change due to internship
      experience except for those who go to missionary hospitals that have stricter
      infection control protocols. More effort must be made in teaching hospitals to
      encourage better infection control.

PMID- 24129626
TI  - Epidemiology of seasonal influenza in Bangkok between 2009 and 2012.
AB  - INTRODUCTION: This study investigated influenza activity in Bangkok, Thailand
      between June 2009 and July 2012. METHODOLOGY: Real-time reverse transcription
      polymerase chain reaction (RT-PCR) was performed to detect influenza viruses
      among patients with influenza-like illnesses. RESULTS: Of the 6417 patients
      tested, influenza virus infection was detected in 42% (n = 2697) of the
      specimens. Influenza A pH1N1 viruses comprised the predominant strain between
      2009 and 2010, and seasonal influenza (H3) had a high prevalence in 2011.
      Laboratory data showed a prevalence and seasonal pattern of influenza viruses. In
      2009, influenza activity peaked in July, the rainy season. In 2010, influenza
      activity happened in two phases, with the initial one at the beginning of the
      year and another peak between June and August 2010, which again corresponded to
      the rainy period. Influenza activity was low for several consecutive weeks at the
      beginning of 2011, and high H3N2 activity was recorded during the rainy season
      between July and September 2011. However, from the beginning of 2012 through July
      2012, pH1N1, influenza H3N2, and influenza B viruses continuously circulated at a
      very low level. CONCLUSION: The seasonal pattern of influenza activity in
      Thailand tended to peak during rainy season between July and September.

PMID- 24129627
TI  - Malnutrition and the presence of intestinal parasites in children from the
      poorest municipalities of Mexico.
AB  - BACKGROUND: For many years Chiapas, Mexico's poorest state, has had the highest
      rate of child mortality due to intestinal infections of unknown etiology in the
      country. To begin identifying the infectious agents, our work determined the
      prevalence of intestinal parasites as well as malnutrition in children from
      Chiapas's three most impoverished municipalities: Pantepec, Chanal, and
      Larrainzar. METHODOLOGY: In this cross-sectional study, conducted between January
      and November 2009, we assessed the prevalence of intestinal parasites by means of
      coproparasitological analysis in children <5 years of age (N=250) from three of
      the marginalized municipalities: Pantepec, Chanal and Larrainzar. The prevalence
      of malnutrition was then assessed using the Mexican official norm NOM-031-SSA2
      1999 and WHO criteria. We evaluated the association between age (breast-fed and
      pre-school children) with parasites and nutritional status. RESULTS: Our analysis
      revealed the highest prevalence of intestinal parasites in children from Pantepec
      (62.8%), followed by Chanal (47.3%), and then Larrainzar (11.9 %). The nematode
      Ascaris lumbricoides was the most prevalent enteroparasite (33.6%).
      Anthropometric analysis revealed that >40% of children represented varying
      degrees of malnutrition and a marked constitutional delay in growth. A very high
      prevalence of stunting was also recorded in children from Chanal and Larrainzar
      (70% and 55%, respectively). An association between infection with intestinal
      parasites and malnutrition was observed in Pantepec. Preschool-age children were
      more likely to be infected with intestinal parasites. CONCLUSION: Our results
      indicate the urgent need for interventions in order to 1) improve the nutritional
      status of children and 2) reduce infection rates of enteric parasites.

PMID- 24129628
TI  - Feasibility and outcome of CT-guided lung biopsy in patients with hematological
      diseases and suspected fungal pneumonia.
AB  - INTRODUCTION: Fungal pneumonia is a major cause of morbidity and mortality in
      immunocompromised patients with hematological diseases. This study is aimed to
      evaluate the feasibility and outcome of computed tomography (CT) guided lung
      biopsy or fine needle aspiration cytology (FNAC) in the diagnosis of fungal
      pneumonia in patients with hematological diseases. METHODOLOGY: Seven hundred and
      seventy six consecutive patients with febrile neutropenia were evaluated
      prospectively over the period of three years. Patients with suspected fungal
      pneumonia, based on typical CT scan findings, were considered for lung biopsy.
      RESULTS: Of the 776 patients evaluated for fever, 235 (30.3%) showed CT scan
      findings consistent with fungal pneumonia. Of the 235 patients, CT-guided lung
      biopsy/FNAC was recommended for 178 patients but could be performed in only 34
      (19.1%) patients. Fungal pneumonia was proven in 15 (44%) out of 34 patients
      (aspergillus in 12; mucormycosis in 3 patients). Lung biopsies could not be
      performed for a number of reasons. These included thrombocytopenia, nodules being
      too small, infection improving with empiric treatment and patient recovering
      clinically, and the patient being too sick to undergo intervention. The median
      absolute neutrophil count (ANC) of patients at the time of lung biopsy was 0.41 x
      109/l in patients whose lung biopsy/FNAC showed fungal pneumonia, compared to
      2.10 x 109/l in patients whose biopsy/FNAC showed necrotizing pneumonitis.
      CONCLUSION: CT-guided lung biopsy/FNAC can allow the definitive diagnosis of
      fungal pneumonia in selected patients with various hematological diseases and
      should be attempted whenever clinically indicated and radiologically feasible.

PMID- 24129629
TI  - Did the cholera epidemic in Haiti really start in the Artibonite Department?

PMID- 24129630
TI  - Low-virulence phylogenetic background of CTX-M-producing Escherichia coli
      isolated from extraintestinal infections.

PMID- 24129631
TI  - 10th anniversary of SARS: China is better prepared for the H7N9 avian influenza
      outbreak.

PMID- 24129632
TI  - Parasitic infections in a Mexican HIV/AIDS cohort.

PMID- 24129633
TI  - Dobrava virus: a mortal agent of hemorrhagic fever with renal syndrome.

PMID- 24129634
TI  - Oxygen reduction at sparse arrays of platinum nanoparticles in aqueous acid:
      hydrogen peroxide as a liberated two electron intermediate.
AB  - Electrodeposition methods are used to generate a sparse array of platinum
      nanoparticles on a glassy carbon electrode. Specifically electrodeposition from a
      1 mM solution of H2PtCl6 in 0.5 M H2SO4 leads to surface coverages of 0.46% to
      1.96% and nanoparticles of size 29 nm to 136 nm in diameter, using deposition
      times of 30 and 15 seconds. The reduction of oxygen at an array of 29 nm
      nanoparticles with a surface coverage of 0.46% showed voltammetric signals with a
      scan rate dependence consistent with a two electron reduction of O2 to H2O2 with
      the rate proportional to K0 exp(-alpha(E-Ef(0))/RT) and formal potential (Ef(0))
      of -0.058 V vs. SHE, a standard electrochemical rate constant (k0) of ~10 cm s(
      1) and a transfer coefficient (alpha) of 0.23. At higher Pt nanoparticle
      coverages, a scan rate dependence consistent with the partial further reduction
      of H2O2 to water becomes evident.

PMID- 24129635
TI  - Black raspberries protectively regulate methylation of Wnt pathway genes in
      precancerous colon tissue.
AB  - Ulcerative colitis is frequently an intermediate step to colon cancer. The
      interleukin-10 knockout mouse is a genetic model of this progression. We report
      that knockout mice fed 5% black raspberries (BRB) had significantly less colonic
      ulceration as compared with knockout mice that consumed the control diet.
      Dysfunction of the Wnt signaling pathway is a key event in ulcerative colitis
      associated colon carcinogenesis. Therefore, we investigated the effects of BRBs
      on the Wnt pathway and found that the BRB-fed knockout mice exhibited a
      significantly lower level of beta-catenin nuclear translocation. We followed-up
      this observation by evaluating the effect of BRBs on selected Wnt pathway
      antagonists. The mRNA expression levels of wif1, sox17, and qki were diminished
      in the knockout mice, whereas they were expressed at normal levels in knockout
      mice that were fed BRBs. The lower mRNA expression of these genes in the colon
      from the knockout mice correlated with hypermethylation of their promoter
      regions; BRBs decreased their promoter methylation and increased mRNA expression
      of these genes. This hypomethylation was associated with elevated protein
      expression of key proteins/enzymes that augment methylation, for example, dnmt3b,
      hdac1, hdac2, and mbd2 in the knockout mice; in addition, BRBs decreased the
      protein expression of these proteins/enzymes. The knockout mouse model
      recapitulates what occurs in human ulcerative colitis. Promoter methylation of
      CDH1 and SFRP1 was significantly higher in human ulcerative colitis tissues
      compared with their adjacent normal tissues. In conclusion, our results suggest
      that BRBs inhibit colonic ulceration and, ultimately, colon cancer partly through
      inhibiting aberrant epigenetic events that dysregulate Wnt signaling.

PMID- 24129637
TI  - Anthocyanin contribution to chlorophyll meter readings and its correction.
AB  - Leaf chlorophyll content is an important physiological parameter which can serve
      as an indicator of nutritional status, plant stress or senescence. Signals
      proportional to the chlorophyll content can be measured non-destructively with
      instruments detecting leaf transmittance (e.g., SPAD-502) or reflectance (e.g.,
      showing normalized differential vegetation index, NDVI) in red and near infrared
      spectral regions. The measurements are based on the assumption that only
      chlorophylls absorb in the examined red regions. However, there is a question
      whether accumulation of other pigments (e.g., anthocyanins) could in some cases
      affect the chlorophyll meter readings. To answer this question, we cultivated
      tomato plants (Solanum lycopersicum L.) for a long time under low light
      conditions and then exposed them for several weeks (4 h a day) to high sunlight
      containing the UV-A spectral region. The senescent leaves of these plants evolved
      a high relative content of anthocyanins and visually revealed a distinct blue
      color. The SPAD and NDVI data were collected and the spectra of diffusive
      transmittance and reflectance of the leaves were measured using an integration
      sphere. The content of anthocyanins and chlorophylls was measured analytically.
      Our results show that SPAD and NDVI measurement can be significantly affected by
      the accumulated anthocyanins in the leaves with relatively high anthocyanin
      content. To describe theoretically this effect of anthocyanins, concepts of a
      specific absorbance and a leaf spectral polarity were developed. Corrective
      procedures of the chlorophyll meter readings for the anthocyanin contribution are
      suggested both for the transmittance and reflectance mode. 

PMID- 24129638
TI  - Digital holography as a method for 3D imaging and estimating the biovolume of
      motile cells.
AB  - Sperm morphology is regarded as a significant prognostic factor for
      fertilization, as abnormal sperm structure is one of the most common factors in
      male infertility. Furthermore, obtaining accurate morphological information is an
      important issue with strong implications in zoo-technical industries, for example
      to perform sorting of species X from species Y. A challenging step forward would
      be the availability of a fast, high-throughput and label-free system for the
      measurement of physical parameters and visualization of the 3D shape of such
      biological specimens. Here we show a quantitative imaging approach to estimate
      simply and quickly the biovolume of sperm cells, combining the optical tweezers
      technique with digital holography, in a single and integrated set-up for a
      biotechnology assay process on the lab-on-a-chip scale. This approach can open
      the way for fast and high-throughput analysis in label-free microfluidic based
      "cytofluorimeters" and prognostic examination based on sperm morphology, thus
      allowing advancements in reproductive science. 

PMID- 24129640
TI  - Clinical and sonographic risk factors for hemiplegic shoulder pain: A
      longitudinal observational study.
AB  - OBJECTIVE: To identify baseline risk factors associated with hemiplegic shoulder
      pain during the first 6 months after a stroke and to investigate changes in these
      risk factors over time. DESIGN: Longitudinal observational study. PATIENTS: A
      total of 94 patients with first-ever unilateral stroke lesion within 1 month
      after stroke. METHODS: Clinical, radiological and sonographic evaluations were
      performed at baseline. Hemiplegic shoulder pain was assessed at 1, 3 and 6 months
      post-stroke. Associations between baseline factors and hemiplegic shoulder pain
      during the first 6 months and hemiplegic shoulder pain at 1, 3 and 6 months
      poststroke were analysed. RESULTS: Poor arm motor function, indicated by a poor
      National Institutes of Health Stroke Scale item 5 score (odds ratio (OR) = 3.0;
      95% confidence interval (CI) = 1.1-7.7) and the presence of supraspinatus tendon
      pathology (OR = 4.2; 95% CI = 1.4-12.9), were associated with hemiplegic shoulder
      pain. While patients with adhesive capsulitis, glenohumeral subluxation, or long
      head of biceps tendon effusion showed a higher prevalence of hemiplegic shoulder
      pain at 1 month after stroke, those with supraspinatus tendon pathology showed a
      higher prevalence at 3 and 6 months. CONCLUSION: Patients at high risk of
      hemiplegic shoulder pain with severe arm paralysis and supraspinatus tendon
      pathology require more careful attention during the rehabilitation period.

PMID- 24129639
TI  - Arabidopsis WAT1 is a vacuolar auxin transport facilitator required for auxin
      homoeostasis.
AB  - The plant hormone auxin (indole-3-acetic acid, IAA) has a crucial role in plant
      development. Its spatiotemporal distribution is controlled by a combination of
      biosynthetic, metabolic and transport mechanisms. Four families of auxin
      transporters have been identified that mediate transport across the plasma or
      endoplasmic reticulum membrane. Here we report the discovery and the functional
      characterization of the first vacuolar auxin transporter. We demonstrate that
      WALLS ARE THIN1 (WAT1), a plant-specific protein that dictates secondary cell
      wall thickness of wood fibres, facilitates auxin export from isolated Arabidopsis
      vacuoles in yeast and in Xenopus oocytes. We unambiguously identify IAA and
      related metabolites in isolated Arabidopsis vacuoles, suggesting a key role for
      the vacuole in intracellular auxin homoeostasis. Moreover, local auxin
      application onto wat1 mutant stems restores fibre cell wall thickness. Our study
      provides new insight into the complexity of auxin transport in plants and a means
      to dissect auxin function during fibre differentiation. 

PMID- 24129641
TI  - Perspectives: should older patients be screened for colorectal cancer?

PMID- 24129642
TI  - Cognitive trajectory after transcatheter aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is known to be
      associated with silent cerebral injury, which could contribute to cognitive
      impairment. Considering its increasing use, thorough longitudinal investigation
      of cognitive trajectory after TAVI is pivotal. METHODS AND RESULTS: Repeatable
      battery for the assessment of neuropsychological status was performed before
      (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI.
      Baseline characteristics, procedural data, imaging parameters of brain injury
      (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches
      were investigated for their effect on cognitive function. Cognitive performance
      was investigated in 111 patients (mean log EuroSCORE, 30+/-13%). Global cognitive
      function (repeatable battery for the assessment of neuropsychological status
      total score) increased transiently at E2 (P=0.02) and was comparable with
      baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early
      cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7%
      and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105
      patients (94.6%), and a majority of patients (91%) demonstrated sustained
      cognitive performance throughout all investigated time points. Interestingly,
      only patient age (P=0.012), but not prior cerebrovascular events, cognitive
      status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a
      cerebral embolic protection device was found to be independently associated with
      cognitive decline, linking higher age to cognitive impairment along the first 2
      years after TAVI. CONCLUSIONS: Long-term cognitive performance was preserved in
      the great majority (91%) of patients throughout the first 2 years after TAVI,
      despite the high intrinsic risk for cognitive deterioration. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883285.

PMID- 24129643
TI  - Application of distraction osteogenesis in managing bone cysts.
AB  - BACKGROUND: Despite the great amount of research concerning bone cysts, there is
      still no commonly accepted method of treatment. The aim of this study was to
      evaluate the effectiveness managing bone cyst with hybrid external fixator by
      distraction osteogenesis. MATERIALS AND METHODS: Between 1982 and 2009, 25
      patients with unicameral (20 patients) and aneurismal (five patients) bone cysts
      were treated using this method. Eighteen patients had a history of pathological
      fracture at the same location. Cysts were located in the humerus, femur, tibia,
      and radius. Median follow-up was 48 (range 31-91) months. Results were evaluated
      on plain radiographs according to the classification system of Capanna et al.
      Functional assessment was done using the modified system recommended by Enneking
      et al. RESULTS: In our study group of 25 bone cysts, 15 were classified as
      completely healed and nine as healed with residual radiolucency. Recurrence was
      observed in one patient. Absence of response to treatment was not observed. All
      patients had excellent functional outcomes, except one with recurrence who was
      rated poor. CONCLUSIONS: As bone cysts are found in long bones in 90-95 % of
      patients, and taking into account our achieved positive results in almost all
      patients, we recommend this method of distraction osteogenesis as a treatment
      option. It is an effective, economical method of treatment, which eliminates
      deformity and restores bone length, especially in patients with pathologic
      fractures.

PMID- 24129644
TI  - The development of highly active acyclic chiral hydrazides for asymmetric iminium
      ion organocatalysis.
AB  - Double asymmetric induction has been employed as a tool to optimise
      pyrazolidinone-derived organocatalysts for the asymmetric iminium ion catalysed
      Diels-Alder reaction. Mechanistic studies revealed a superior hydrazide catalyst
      deriving from methanolysis of the chiral pyrazolidinone precursor. This catalyst
      displays unusually high endo diastereoselectivity and good enantioselectivity
      with a range of beta-arylenals and cyclic dienes at catalyst loadings as low as 1
      mol%. 

PMID- 24129645
TI  - No-go neurons in the cerebellar oculomotor vermis and caudal fastigial nuclei:
      planning tracking eye movements.
AB  - The cerebellar dorsal vermis lobules VI-VII (oculomotor vermis) and its output
      region (caudal fastigial nuclei, cFN) are involved in tracking eye movements
      consisting of both smooth-pursuit and saccades, yet, the exact role of these
      regions in the control of tracking eye movements is still unclear. We compared
      the neuronal discharge of these cerebellar regions using a memory-based, smooth
      pursuit task that distinguishes discharge related to movement preparation and
      execution from the discharge related to the processing of visual motion signals
      or their memory. Monkeys were required to pursue (i.e., go), or not pursue (i.e.,
      no-go) in a cued direction, based on the memory of visual motion direction and
      go/no-go instructions. Most (>60 %) of task-related vermal Purkinje cells (P
      cells) and cFN neurons discharged specifically during the memory period following
      no-go instructions; their discharge was correlated with memory of no-go
      instructions but was unrelated to eye movements per se during the action period
      of go trials. The latencies of no-go discharge of vermal P-cells and cFN neurons
      were similar, but were significantly longer than those of supplementary eye field
      (SEF) no-go neurons during an identical task. Movement-preparation signals were
      found in ~30 % of smooth-pursuit-related neurons in these cerebellar regions and
      some of them also carried visual memory signals. Our results suggest that no-go
      neurons are a newly revealed class of neurons, detected using the memory-based
      pursuit task, in the oculomotor vermis-cFN pathway and that this pathway
      contributes specifically to planning requiring the working memory of no-go
      instructions and preparation of tracking eye movements.

PMID- 24129647
TI  - Multisensory integration compensates loss of sensitivity of visual temporal order
      in the elderly.
AB  - Here, we examined sensitivity of visual, auditory, and audiovisual temporal order
      in five age-groups (20 to 70 years old). We also measured multisensory
      integration (MSI) using a phenomenon known as "temporal ventriloquism," in which
      click sounds improve sensitivity of visual temporal order. Results showed that
      sensitivity of visual, auditory, and audiovisual temporal order declined from 50
      years on. However, there was no corresponding decline in MSI as the click sounds
      actually compensated the loss of sensitivity of visual temporal order in the
      elderly. Sensitivity of audiovisual temporal order did not correlate with MSI,
      suggesting that well-preserved explicit judgments about cross-modal temporal
      order are not required for MSI to occur.

PMID- 24129648
TI  - Preferences on policy options for ensuring the financial sustainability of health
      care services in the future: results of a stakeholder survey.
AB  - BACKGROUND: Universal access to health care in most western European countries
      has been a given for many decades; however, macroeconomic developments and
      increased pressure on health care budgets could mean the status quo cannot be
      maintained. As populations age, a declining proportion of economically active
      citizens are being required to support a larger burden of health and social care,
      while increasing availability of novel technologies for extending and improving
      life continues to push health care costs upwards. With health expenditure
      continuing to rise as a proportion of national income, concerns are raised about
      the current and future financial sustainability of Organisation for Economic Co
      Operation and Development (OECD) health care systems. Against this backdrop, a
      discussion about options to fund health care in the future, including whether to
      raise additional health care finance (and the ways to do so), reallocate
      resources and/or ration services becomes very pertinent. OBJECTIVE: This study
      elicits preferences among a group of key stakeholders (payers, providers,
      government, academia and health-related industry) on the issue of health care
      financial sustainability and the future funding of health care services, with a
      view to understanding the different degrees of acceptability between policy
      interventions and future funding options as well as their feasibility. STUDY
      DESIGN AND PARTICIPANTS: We invited 842 individuals from academia, other research
      organisations (eg. think tanks), national health services, providers, health
      insurance organisations, government representatives and health-related industry
      and related advisory stakeholders to participate in an online survey collecting
      preferences on a variety of revenue-generating mechanisms and cost/demand
      reducing policies. Respondents represented the 28 EU member states as well as
      Norway, Iceland, Switzerland, Australia, Russian Federation, Canada and New
      Zealand. RESULTS: We received 494 responses to our survey from all stakeholder
      groups. Across all groups, the highest preference was for policies to modify
      lifestyle and implement more extensive screening within risk groups for high
      burden illnesses. There was a broad consensus not to reallocate resources from
      social security/education. Between stakeholders, there were differences of
      opinion between industry/advisory and a range of other groups, with industry
      being generally more in favour of market-based interventions and an increased
      role for the private sector in health care financing/delivery. Conversely,
      stakeholders from academia, government, national health services and insurance
      were relatively more in favour of more restrictive purchasing of new and
      expensive technologies, and (to varying extent) of higher income/corporate taxes.
      Taxes on cigarettes/alcohol were by far considered the most politically feasible
      option. CONCLUSIONS: According to this study, policy options that are broadly
      acceptable across stakeholder groups with different inherent interests exist but
      are limited to lifestyle modification, screening interventions and excise taxes
      on harmful products. Representatives from the private sector tend to view
      solutions rooted in the private sector as both effective and politically feasible
      options, while stakeholders from academia and the public sector seem to place
      more emphasis on solutions that do not disproportionately impact certain
      population groups.

PMID- 24129649
TI  - Are the true impacts of adverse events considered in economic models of
      antineoplastic drugs? A systematic review.
AB  - BACKGROUND: Antineoplastic drugs for cancer are often associated with adverse
      events, which influence patients' physical health, quality of life and survival.
      However, the modelling of adverse events in cost-effectiveness analyses of
      antineoplastic drugs has not been examined. AIMS: This article reviews published
      economic evaluations that include a calculated cost for adverse events of
      antineoplastic drugs. The aim is to identify how existing models manage four
      issues specific to antineoplastic drug adverse events: the selection of adverse
      events for inclusion in models, the influence of dose modifications on drug
      quantity and survival outcomes, the influence of adverse events on quality of
      life and the consideration of multiple simultaneous or recurring adverse events.
      METHODS: A systematic literature search was conducted using MESH headings and key
      words in multiple electronic databases, covering the years 1999-2009. Inclusion
      criteria for eligibility were papers covering a population of adults with solid
      tumour cancers, the inclusion of at least one adverse event and the resource use
      and/or costs of adverse event treatment. RESULTS: From 4,985 citations, 26
      eligible articles were identified. Studies were generally of moderate quality and
      addressed a range of cancers and treatment types. While the four issues specific
      to antineoplastic drug adverse events were addressed by some studies, no study
      addressed all of the issues in the same model. CONCLUSION: This review indicates
      that current modelling assumptions may restrict our understanding of the true
      impact of adverse events on cost effectiveness of antineoplastic drugs. This
      understanding could be improved through consideration of the selection of adverse
      events, dose modifications, multiple events and quality of life in cost
      effectiveness studies.

PMID- 24129650
TI  - Atomic resolution liquid-cell transmission electron microscopy investigations of
      the dynamics of nanoparticles in ultrathin liquids.
AB  - We proposed a highly reproducible method that enables atomic resolution
      transmission electron microscopy investigations of the dynamics of nanoparticles
      in liquids. An ultrathin liquid layer was established as a result of formation of
      bubbles that was initiated and tuned by beam radiation. The migration,
      aggregation and rotation of palladium nanoparticles were observed. 

PMID- 24129651
TI  - Computational screening of functionalized zinc porphyrins for dye sensitized
      solar cells.
AB  - An efficient dye sensitized solar cell (DSSC) is one possible solution to meet
      the world's rapidly increasing energy demands and associated climate challenges.
      This requires inexpensive and stable dyes with well-positioned frontier energy
      levels for maximal solar absorption, efficient charge separation, and high output
      voltage. Here we demonstrate an extensive computational screening of zinc
      porphyrins functionalized with electron donating side groups and electron
      accepting anchoring groups. The trends in frontier energy levels versus side
      groups are analyzed and a no-loss DSSC level alignment quality is estimated. Out
      of the initial 1029 molecules, we find around 50 candidates with level alignment
      qualities within 5% of the optimal limit. We show that the level alignment of
      five zinc porphyrin dyes which were recently used in DSSCs with high efficiencies
      can be further improved by simple side group substitutions. All frontier energy
      levels, gaps and level alignment quality values are stored in a database publicly
      available. 

PMID- 24129652
TI  - Magneto-electric nanoparticles to enable field-controlled high-specificity drug
      delivery to eradicate ovarian cancer cells.
AB  - The nanotechnology capable of high-specificity targeted delivery of anti
      neoplastic drugs would be a significant breakthrough in Cancer in general and
      Ovarian Cancer in particular. We addressed this challenge through a new physical
      concept that exploited (i) the difference in the membrane electric properties
      between the tumor and healthy cells and (ii) the capability of magneto-electric
      nanoparticles (MENs) to serve as nanosized converters of remote magnetic field
      energy into the MENs' intrinsic electric field energy. This capability allows to
      remotely control the membrane electric fields and consequently trigger high
      specificity drug uptake through creation of localized nano-electroporation sites.
      In in-vitro studies on human ovarian carcinoma cell (SKOV-3) and healthy cell
      (HOMEC) lines, we applied a 30-Oe d.c. field to trigger high-specificity uptake
      of paclitaxel loaded on 30-nm CoFe2O4 @BaTiO3 MENs. The drug penetrated through
      the membrane and completely eradicated the tumor within 24 hours without
      affecting the normal cells.

PMID- 24129653
TI  - Design and validation of automated femoral bone morphology measurements in
      cerebral palsy.
AB  - Accurate quantification of bone morphology is important for monitoring the
      progress of bony deformation in patients with cerebral palsy. The purpose of the
      study was to develop an automatic bone morphology measurement method using one or
      two radiographs. The study focused on four morphologic measurements-neck-shaft
      angle, femoral anteversion, shaft bowing angle, and neck length. Fifty-four three
      dimensional (3D) geometrical femur models were generated from the computed
      tomography (CT) of cerebral palsy patients. Principal component analysis was
      performed on the combined data of geometrical femur models and manual
      measurements of the four morphologic measurements to generate a statistical femur
      model. The 3D-2D registration of the statistical femur model for radiography
      computes four morphological measurements of the femur in the radiographs
      automatically. The prediction performance was tested here by means of leave-one
      out cross-validation and was quantified by the intraclass correlation coefficient
      (ICC) and by measuring the absolute differences between automatic prediction from
      two radiographs and manual measurements using original CT images. For the neck
      shaft angle, femoral anteversion, shaft bowing angle, and neck length, the ICCs
      were 0.812, 0.960, 0.834, and 0.750, respectively, and the mean absolute
      differences were 2.52 degrees , 2.85 degrees , 0.92 degrees , and 1.88 mm,
      respectively. Four important dimensions of the femur could be predicted from two
      views with very good agreement with manual measurements from CT and hip
      radiographs. The proposed method can help young patients avoid instances of large
      radiation exposure from CT, and their femoral deformities can be quantified
      robustly and effectively from one or two radiograph(s).

PMID- 24129654
TI  - [Innate immunity and allergy].

PMID- 24129655
TI  - [Basophil and allergy].

PMID- 24129656
TI  - [Guidelines for contact dermatitis -one point advice-].

PMID- 24129657
TI  - [Towards evidence-based guidelines for evaluation and management of urticaria].

PMID- 24129658
TI  - [Role of IL-17 family cytokines in allergic inflammation].

PMID- 24129659
TI  - [Case of atopic dermatitis in infant treated with Chinese herbal medicines and
      nsaids ointment, which induced weight loss, electrolyte disturbance and
      hypoproteinemia].
AB  - We report here a 4-month-old girl with atopic dermatitis accompanied by weight
      loss, electrolyte disturbance, hypoproteinemia and hypogammaglobulinemia. She has
      suffered from eczema since one-month of age. Although she was treated with
      Chinese herbal medicines, including Syosaikotokakikyosekko,
      Tokishigyakukagoshuyushokyoto and Jumihaidokuto and ibuprofen ointment since
      three-month of age, she was referred to our hospital due to deteriorated eczema,
      severe diarrhea and failure to thrive. Laboratory examination revealed
      hyponatremia, hyperpotassemia, hypoproteinemia, hypogammaglobulinemia and
      elevated levels of serum IL-18, TARC and fecal EDN. Drug-induced lymphocyte
      stimulation tests were positive for the prescribed Chinese herbal medicines.
      Discontinuation of these medicines and application of steroid ointments improved
      loose bowels and skin lesions as well as laboratory data. It is suggested that
      the application of inadequate ointment and Chinese herbal medicines exaggerated
      inflammation in the skin and the intestinal mucosa leading to electrolyte
      disturbance, hypoproteinemia and hypogammaglobulinemia. Chinese herbal medicines
      are depicted as an additional therapy in Japanese guideline for atopic
      dermatitis, whereas their indication to infants with atopic dermatitis should be
      carefully assessed. 

PMID- 24129660
TI  - A plasma-treated chalcogenide switch device for stackable scalable 3D nanoscale
      memory.
AB  - Stackable select devices such as the oxide p-n junction diode and the Schottky
      diode (one-way switch) have been proposed for non-volatile unipolar resistive
      switching devices; however, bidirectional select devices (or two-way switch) need
      to be developed for bipolar resistive switching devices. Here we report on a
      fully stackable switching device that solves several problems including current
      density, temperature stability, cycling endurance and cycle distribution. We
      demonstrate that the threshold switching device based on As-Ge-Te-Si material
      significantly improves cycling endurance performance by reactive nitrogen
      deposition and nitrogen plasma hardening. Formation of the thin Si3N4 glass layer
      by the plasma treatment retards tellurium diffusion during cycling. Scalability
      of threshold switching devices is measured down to 30 nm scale with extremely
      fast switching speed of ~2 ns.

PMID- 24129661
TI  - Alcohol-attributable and alcohol-preventable mortality in Denmark: an analysis of
      which intake levels contribute most to alcohol's harmful and beneficial effects.
AB  - The aim of the study was to quantify alcohol-attributable and -preventable
      mortality, totally and stratified on alcohol consumption in Denmark 2010, and to
      estimate alcohol-related mortality assuming different scenarios of changes in
      alcohol distribution in the population. We estimated alcohol-attributable and 
      preventable fractions based on relative risks of conditions causally associated
      with alcohol from meta-analyses and information on alcohol consumption in Denmark
      obtained from 14,458 participants in the Danish National Health Survey 2010 and
      corrected for adult per capita consumption. Cause-specific mortality data were
      obtained from the Danish Register of Causes of Death. In total, 1,373 deaths
      among women (5.0% of all deaths) and 2,522 deaths among men (9.5% of all deaths)
      were attributable to alcohol, while an estimated number of 765 (2.8%) and 583
      (2.2%) deaths were prevented by alcohol. Of the alcohol-attributable deaths, 73
      and 81% occurred within the high alcohol consumption group (>14/21 drinks/week
      for women/men). A reduction of 50% in the alcohol consumption was associated with
      a decrease of 1,406 partly alcohol-attributable deaths (46%) and 37 alcohol
      preventable deaths (3%). Total compliance with sensible drinking guidelines with
      a low risk limit (<7/14 drinks/week) and a high risk limit (<14/21 drinks/week)
      was associated with a reduction of 2,380 and 1,977 alcohol-attributable deaths,
      respectively. In summary, 5.0% of deaths among women and 9.5 % of deaths among
      men were attributable to alcohol in Denmark 2010. The minority of Danish women
      and men had high alcohol consumption (16 and 26%). However, the majority of all
      alcohol-attributable deaths among women and men were caused by high consumption
      (73 and 81%).

PMID- 24129662
TI  - Forensic implications: adolescent sexting and cyberbullying.
AB  - Adolescence is marked by establishing a sense of identity, core values, a sense
      of one's relationship to the outside world and heightened peer relationships. In
      addition, there is also risk taking, impulsivity, self exploration and dramatic
      increase in sexuality. The dramatic increase in the use of cell phones and the
      Internet has additional social implications of sexting and cyberbullying. Sexting
      refers to the practice of sending sexually explicit material including language
      or images to another person's cell phone. Cyberbullying refers to the use of this
      technology to socially exclude, threaten, insult or shame another person. Studies
      of cell phone use in the 21st century report well over 50% of adolescents use
      them and that text messaging is the communication mode of choice. Studies also
      show a significant percentage of adolescents send and receive sex messaging, both
      text and images. This paper will review this expanding literature. Various
      motivations for sexting will also be reviewed. This new technology presents many
      dangers for adolescents. The legal implications are extensive and psychiatrists
      may play an important role in evaluation of some of these adolescents in the
      legal context. This paper will also make suggestions on future remedies and
      preventative actions.

PMID- 24129663
TI  - Phloretin-induced reduction in dipole potential of sterol-containing bilayers.
AB  - The phloretin-induced reduction in the dipole potential of planar lipid bilayers
      containing cholesterol, ergosterol, stigmasterol, 7-dehydrocholesterol and 5alpha
      androstan-3beta-ol was investigated. It is shown that effects depend on the type
      and concentration of membrane sterol. It is supposed that the effectiveness of
      phloretin in reducing the dipole potential of the bilayers that contain
      cholesterol, ergosterol and 7-dehydrocholesterol correlates with the ordering and
      condensing effects. The role of the concentration-dependent ability of different
      sterols to promote lateral heterogeneity in membranes is also discussed. 

PMID- 24129665
TI  - Efficient and regioselective nickel-catalyzed [2 + 2 + 2] cyclotrimerization of
      ynoates and related alkynes.
AB  - A nickel-based catalytic system has been developed for [2 + 2 + 2]
      cyclotrimerization of various alkynes, especially ynoates. This catalytic system
      enables facile construction of substituted aromatic compounds in excellent yields
      with high regioselectivity. 

PMID- 24129666
TI  - Hemoglobin stability and patient satisfaction after switch to C.E.R.A. therapy: a
      multicenter, observational study.

PMID- 24129667
TI  - Optical waves in a gradient negative-index lens of a half-infinite length.
AB  - Materials with negative permittivity and permeability can overcome the
      diffraction limit, thereby making the sub-wavelength imaging possible. In this
      study, we analyze the effects of gradient index on a half-infinite perfect lens.
      We assume that the sharp interface between the vacuum and the negative-index
      material is replaced by a smooth transition profile such that the index gradually
      changing from positive to negative. Interestingly, we find that if the graded
      index profile is modeled by a tanh function, we can have closed-form analytical
      solutions for this problem, which is a distinct advantage as numerical solutions
      are not accurate for evanescent waves with large transverse wave vectors. By
      analyzing the analytical formulas we confirm that a nonzero total absorption can
      occur even for a near-zero absorption coefficient in the steady-state limit and
      the image plane contains multiple sub-wavelength images of an object. 

PMID- 24129668
TI  - Meta-analysis shows clinically relevant and long-lasting deterioration in health
      related quality of life after esophageal cancer surgery.
AB  - PURPOSE: The purpose of the study is to (1) estimate the direction, clinical
      relevance, and duration of health-related quality of life (HRQL) change in the
      first year following esophageal cancer surgery and (2) to assess the robustness
      of the estimates by subgroup and sensitivity analyses, and an exploration of
      publication bias. METHODS: A systematic literature search in MEDLINE, EMBASE,
      CINAHL, PsychINFO, and CENTRAL to identify randomized and non-randomized studies
      was performed. We compared the baseline HRQL data with 3-, 6-, 9-, or 12-month
      follow-ups to estimate the magnitude and duration of HRQL change. These estimates
      were then classified as trivial, small, medium, or large. Primary outcomes were
      role functioning, eating, and fatigue. Secondary outcomes were physical and
      social functioning, dysphagia, pain, and coughing problems. We conducted subgroup
      analysis for open surgery, open surgery preceded by neo-adjuvant therapy, and
      minimally invasive surgery. Sensitivity analyses assessed the influence of study
      design, transformation/imputation of the data, and HRQL questionnaire used.
      RESULTS: We included data from 15 studies to estimate the change in 28 HRQL
      outcomes after esophageal cancer surgery. The main analysis showed that patients'
      social functioning deteriorated. Symptoms of fatigue, pain, and coughing problems
      increased. These changes lasted for 9-12 months, although some symptoms persisted
      beyond the first year after surgery. For many other HRQL outcomes, estimates were
      only robust after subgroup or sensitivity analyses (e.g., role and physical
      functioning), or remained too heterogeneous to interpret (e.g., eating and
      dysphagia). CONCLUSIONS: Patients will experience a clinically relevant and long
      lasting deterioration in HRQL after esophageal cancer surgery. However, for many
      HRQL outcomes, more and better quality evidence is needed.

PMID- 24129669
TI  - Joint models for predicting transplant-related mortality from quality of life
      data.
AB  - PURPOSE: To test whether longitudinally measured health-related quality of life
      (HRQL) predicts transplant-related mortality (TRM) in pediatric hematopoietic
      stem cell transplant (HSCT). METHODS: The predictors of interest were emotional
      functioning, physical functioning, role functioning, and global HRQL, as rated by
      the parent about the child up to 6 times over 12 months of follow-up and measured
      by the Child Health Ratings Inventories. We used joint models, specifically
      shared parameter models, with time to TRM as the outcome of interest and other
      causes of mortality as a competing risk, via the JM software package in R.
      Choosing shared parameter models instead of standard survival models, such as Cox
      models with time-dependent covariates, enabled us to address measurement error in
      the HRQL trajectories and appropriately handle missing data. The nonlinear
      trajectories for each HRQL domain were modeled by random spline functions. The
      survival submodels were adjusted for baseline patient, family, and transplant
      characteristics. RESULTS: Hazard ratios per one-half standard deviation
      difference in emotional, physical, and role functioning, and global HRQL were
      0.61 (95 % CI 0.46-0.81; p < 0.001), 0.70 (0.51-0.96; p = 0.03), 0.54 (0.34-0.85;
      p = 0.007), and 0.57 (0.41-0.79; p < 0.001), respectively. CONCLUSIONS: HRQL
      trajectories were predictive of TRM in pediatric HSCT, even after adjusting the
      survival outcome for baseline characteristics.

PMID- 24129670
TI  - Identifying vulnerability in grief: psychometric properties of the Adult Attitude
      to Grief Scale.
AB  - PURPOSE: Grief is a reaction to a significant loss that can profoundly affect all
      aspects of life and capacity to function well. The consequences can vary from
      severe psychological distress through to physical disturbances and significant
      social problems. This study sought to identify a measure of vulnerability in
      grief, by examining the psychometric properties of the Adult Attitude to Grief
      (AAG) scale in a sample of 168 people seeking help in their bereavement. METHODS:
      The factor structure of the scale, its internal consistency, its construct
      validity and optimum classification cutoffs were tested. RESULTS: Confirmatory
      factor analysis broadly supported the factor structure of the AAG, but identified
      one item that could profitably be reworded. Internal consistency of the three
      subscales was acceptable. Construct validity and discriminative validity were
      supported by correlations with allied constructs (depression and anxiety) and a
      significant difference between scores for clients with Prolonged Grief Disorder
      and those without. A correlation with counsellors' own clinical ratings of
      vulnerability demonstrated criterion-related validity of the AAG. Using receiver
      operating characteristic methods, optimum cutoff scores on the scale were
      identified for the classification of different levels of vulnerability.
      CONCLUSION: The AAG was found to be a psychometrically promising tool for
      identifying vulnerability in grief.

PMID- 24129671
TI  - Validating the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) in
      Italian inpatients with chronic migraine with a history of medication overuse.
AB  - PURPOSE: The purpose of the study is to assess validity, reliability and factor
      structure of the Italian version of Migraine-Specific Quality of Life
      Questionnaire v2.1 (MSQ) in patients suffering from chronic migraine (CM) with a
      history of medication overuse (MO). METHODS: Patients were enrolled at hospital
      admission for withdrawal from MO. Factor analysis was used to confirm the latent
      structure of the MSQ. Reliability was measured with Cronbach's alpha coefficient,
      item-total correlation and inter-item correlation. Construct validity was
      assessed with Pearson's coefficient and known-group analysis. RESULTS: The three
      factor structure is basically confirmed. Cronbach's alpha varied between 0.85 and
      0.92; item-total correlations were on average higher than 0.70; average inter
      item correlation ranged between 0.63 and 0.65. Correlations were all significant;
      known-group analysis shows that MSQ score was lower consistently with disease
      severity. CONCLUSIONS: Our findings confirm the factor structure, reliability and
      validity of the MSQ and expand results of previous validation studies to the
      Italian language and to a group of patients with severe CM requiring withdrawal
      treatment for MO.

PMID- 24129672
TI  - The impact of weight loss on health-related quality-of-life: implications for
      cost-effectiveness analyses.
AB  - PURPOSE: To assess the impact of weight loss on health-related quality-of-life
      (HRQL), to describe the factors associated with improvements in HRQL after weight
      loss, and to assess the relationship between obesity as assessed by body mass
      index (BMI) and HRQL before and after weight loss. METHODS: We studied 188 obese
      patients with BMI >= 32 kg/m(2) with one or more comorbidities or >=35 kg/m(2).
      All patients had baseline and follow-up assessments of BMI and HRQL using the
      EuroQol (EQ-5D) and its visual analog scale (VAS) before and after 6 months of
      medical weight loss that employed very low-calorie diets, physical activity, and
      intensive behavioral counseling. RESULTS: At baseline, age was 50 +/- 8 years
      (mean +/- SD), BMI was 40. 0 +/- 5.0 kg/m(2), EQ-5D-derived health utility score
      was 0.85 +/- 0.13, and VAS-reported quality-of-life was 0.67 +/- 0.18. At 6-month
      follow-up, BMI decreased by 7.0 +/- 3.2 kg/m(2), EQ-5D increased by 0.06
      [interquartile range (IQR) 0.06-0.17], and VAS increased by 0.14 (IQR 0.04-0.23).
      In multivariate analyses, improvement in EQ-5D and VAS were associated with lower
      baseline BMI, greater reduction in BMI at follow-up, fewer baseline
      comorbidities, and lower baseline HRQL. For any given BMI category, EQ-5D and VAS
      tended to be higher at follow-up than at baseline. CONCLUSION: Measured
      improvements in HRQL between baseline and follow-up were greater than predicted
      by the reduction in BMI at follow-up. If investigators use cross-sectional data
      to estimate changes in HRQL as a function of BMI, they will underestimate the
      improvement in HRQL associated with weight loss and underestimate the cost
      utility of interventions for obesity treatment.

PMID- 24129673
TI  - Coexistent skin lesions of vitiligo and psoriasis vulgaris. Immunohistochemical
      analyses for IL-17A-producing cells and regulatory T cells.

PMID- 24129675
TI  - Genetic analysis and molecular mapping of a new fertility restorer gene Rf8 for
      Triticum timopheevi cytoplasm in wheat (Triticum aestivum L.) using SSR markers.
AB  - A study on mode of inheritance and mapping of fertility restorer (Rf) gene(s)
      using simple sequence repeat (SSR) markers was conducted in a cross of male
      sterile line 2041A having Triticum timopheevi cytoplasm and a restorer line
      PWR4099 of common wheat (Triticum aestivum L.). The F1 hybrid was completely
      fertile indicating that fertility restoration is a dominant trait. Based on the
      pollen fertility and seed set of bagged spikes in F2 generation, the individual
      plants were classified into fertile and sterile groups. Out of 120 F2 plants, 97
      were fertile and 23 sterile (based on pollen fertility) while 98 plants set >= 5
      seeds/spike and 22 produced <= 4 or no seed. The observed frequency fits well
      into Mendelian ratio of 3 fertile: 1 sterile with chi(2) value of 2.84 for pollen
      fertility and 2.17 for seed setting indicating that the fertility restoration is
      governed by a single dominant gene in PWR4099. The three linked SSR markers,
      Xwmc503, Xgwm296 and Xwmc112 located on the chromosome 2DS were placed at a
      distance of 3.3, 5.8 and 6.7 cM, respectively, from the Rf gene. Since, no known
      Rf gene is located on the chromosome arm 2DS, the Rf gene in PWR4099 is a new
      gene and proposed as Rf8. The closest SSR marker, Xwmc503, linked to the Rf8 was
      validated in a set of Rf, maintainer and cytoplasmic male sterile lines. The
      closely linked SSR marker Xwmc503 may be used in marker-assisted backcross
      breeding facilitating the transfer of fertility restoration gene Rf8 into elite
      backgrounds with ease.

PMID- 24129674
TI  - Synergetic regulatory networks mediated by oncogene-driven microRNAs and
      transcription factors in serous ovarian cancer.
AB  - Although high-grade serous ovarian cancer (OVC) is the most lethal gynecologic
      malignancy in women, little is known about the regulatory mechanisms in the
      cellular processes that lead to this cancer. Recently, accumulated lines of
      evidence have shown that the interplay between transcription factors (TFs) and
      microRNAs (miRNAs) is critical in cellular regulation during tumorigenesis. A
      comprehensive investigation of TFs and miRNAs, and their target genes, may
      provide a deeper understanding of the regulatory mechanisms in the pathology of
      OVC. In this study, we have integrated three complementary algorithms into a
      framework, aiming to infer the regulation by miRNAs and TFs in conjunction with
      gene expression profiles. We demonstrated the utility of our framework by
      inferring 67 OVC-specific regulatory feed-forward loops (FFL) initiated by miRNAs
      or TFs in high-grade serous OVC. By analyzing these regulatory behaviors, we
      found that all the 67 FFLs are consistent in their regulatory effects on genes
      that are jointly targeted by miRNAs and TFs. Remarkably, we unveiled an
      unbalanced distribution of FFLs with different oncogenic effects. In total, 31 of
      the 67 coherent FFLs were mainly initiated by oncogenes. On the contrary, only 4
      of the FFLs were initiated by tumor suppressor genes. These overwhelmingly
      observed oncogenic genes were further detected in a sub-network with 32 FFLs
      centered by miRNA let-7b and TF TCF7L1 to regulate cell differentiation. Closer
      inspection of 32 FFLs revealed that 75% of the miRNAs reportedly play functional
      roles in cell differentiation, especially when enriched in epithelial-mesenchymal
      transitions. This study provides a comprehensive pathophysiological overview of
      recurring coherent circuits in OVC that are co-regulated by miRNAs and TFs. The
      prevalence of oncogenic coherent FFLs in serous OVC suggests that oncogene-driven
      regulatory motifs could cooperatively act upon critical cellular processes such
      as cell differentiation in a highly efficient and consistent manner. 

PMID- 24129676
TI  - Regeneration of optic nerve fibers with unoprostone, a prostaglandin-related
      antiglaucoma drug, in adult cats.
AB  - PURPOSE: We investigated the effects of unoprostone on neurite extension of
      cultured retinal pieces and axonal regeneration of retinal ganglion cells in the
      crushed optic nerve of adult cats. METHODS: The retinal pieces were cultured with
      unoprostone or its primary metabolite, M1, dissolved in DMSO or polysorbate for
      14 days, and the number and length of Tau-1-positive neurites and glial processes
      labeled with anti-glial fibrillary acidic protein antibodies were examined. After
      the optic nerve was crushed, unoprostone was injected into the vitreous body and
      the crushed site. On day 12, wheat germ agglutinin-conjugated horseradish
      peroxidase was injected into the vitreous body to anterogradely label the
      regenerated axons. On day 14, the optic nerve was excised and longitudinally
      sectioned. After peroxidase reaction, the number of axons regenerating beyond the
      crush site was examined. RESULTS: The greatest number of neurites protruded from
      the cultured retinal pieces in 3 MUM unoprostone and 3 MUM M1. The neurite length
      was also the longest at 3 MUM unoprostone and 3 MUM M1, in which no glial
      processes were detected. After injections of 3 MUM unoprostone, the final
      concentration in the vitreous humor, into the vitreous body and the crush site,
      the optic nerve fibers regenerated and extended beyond the crush site. In
      contrast, almost no fibers extended beyond the crush site after injection of
      phosphate-buffered saline. CONCLUSIONS: The results indicate that intravitreal
      injection of unoprostone promotes regeneration of crushed optic nerve fibers in
      adult cats.

PMID- 24129678
TI  - Janus-like Pickering emulsions and their controllable coalescence.
AB  - Janus-like emulsions stabilized by OH(-) and polydopamine (PDA) particles were
      realized. The OH(-) and particle occupied areas on emulsion droplet surfaces are
      spatially separated. Via controlling the pH and ionic strength, the coalescence
      of Janus-like emulsion droplets could be manipulated. 

PMID- 24129677
TI  - Clinical course of patients with Behcet's uveitis following discontinuation of
      infliximab therapy.
AB  - PURPOSE: To investigate the clinical course of Behcet's uveitis patients
      following discontinuation of infliximab therapy. METHODS: This retrospective
      chart review study examined Behcet's disease patients who received infliximab
      treatment between 2000 and 2012. Medical records of patients whose infliximab
      treatment was discontinued were reviewed, with special focus on the frequency of
      uveitis attacks in the period before initiation, during treatment and after
      cessation of the infliximab therapy. Mean visual acuities were evaluated for each
      treatment period. RESULTS: Out of the 43 patients treated with infliximab at our
      uveitis clinic, ten were discontinued due to adverse events or inefficiency. Data
      for seven patients followed for more than 12 months before initiation and after
      cessation of infliximab were analyzed. Frequency of acute uveitis attacks was
      7.43 per 12 months before initiation of infliximab, 2.86 during treatment and
      0.57 after cessation. A statistically higher frequency of uveitis attacks was
      observed before initiation of infliximab compared to during (p < 0.05) and after
      cessation of treatment (p < 0.05). There was no statistical significance observed
      between the period during treatment and after cessation (p = 0.29). The mean
      logMAR was 0.79 at baseline, 0.68 during treatment, and 0.88 at 12 months after
      cessation. These differences were not statistically significant. CONCLUSIONS: A
      satisfactory clinical course with well-controlled ocular inflammation was found
      after discontinuation of infliximab therapy in Behcet's uveitis patients. These
      results suggest that a safe, pre-planned discontinuation of infliximab therapy
      can be performed in patients with Behcet's uveitis.

PMID- 24129679
TI  - Skin tumorigenesis stimulated by Raf inhibitors relies upon Raf functions that
      are dependent and independent of ERK.
AB  - RAF inhibitors achieve unprecedented but mainly transient clinical responses in
      patients with melanoma whose tumors harbor an activating BRAF mutation. One
      notable side-effect of RAF inhibitors is the stimulation of cutaneous skin
      tumors, arising in about 30% of patients receiving these drugs, which are thought
      to develop as a result of inhibitor-induced activation of wild-type Raf in occult
      precursor skin lesions. This effect raises the possibility that less manageable
      tumors might also arise in other epithelial tissues. Here we provide preclinical
      evidence supporting this disquieting hypothesis by showing that the RAF
      inhibitors PLX-4032 (vemurafenib) and GDC-0879 precipitate the development of
      cell-autonomous, Ras-driven tumors in skin and gastric epithelia. The magnitude
      of the effects correlated with the inhibitors' relative abilities to induce ERK
      activation. Epidermis-restricted ablation of either B-Raf or C-Raf prevented PLX
      4032-induced ERK activation and tumorigenesis. In contrast, GDC-0879 induced ERK
      activation and tumorigenesis in B-Raf-deficient epidermis, whereas C-Raf ablation
      blocked GDC-0879-induced tumorigenesis (despite strong ERK activation) by
      preventing Rokalpha-mediated keratinocyte dedifferentiation. Thus, inhibitor
      induced ERK activation did not require a specific Raf kinase. ERK activation was
      necessary, but not sufficient for Ras + Raf inhibitor-induced tumorigenesis,
      whereas C-Raf downregulation of Rokalpha was essential even in the face of
      sustained ERK signaling to prevent differentiation and promote tumorigenesis.
      Taken together, our findings suggest that combination therapies targeting ERK
      dependent and -independent functions of Raf may be more efficient but also safer
      for cancer treatment.

PMID- 24129680
TI  - Three-dimensional self-assembled photonic crystals with high temperature
      stability for thermal emission modification.
AB  - Selective thermal emission in a useful range of energies from a material
      operating at high temperatures is required for effective solar thermophotovoltaic
      energy conversion. Three-dimensional metallic photonic crystals can exhibit
      spectral emissivity that is modified compared with the emissivity of unstructured
      metals, resulting in an emission spectrum useful for solar thermophotovoltaics.
      However, retention of the three-dimensional mesostructure at high temperatures
      remains a significant challenge. Here we utilize self-assembled templates to
      fabricate high-quality tungsten photonic crystals that demonstrate unprecedented
      thermal stability up to at least 1,400  degrees C and modified thermal emission
      at solar thermophotovoltaic operating temperatures. We also obtain comparable
      thermal and optical results using a photonic crystal comprising a previously
      unstudied material, hafnium diboride, suggesting that refractory metallic ceramic
      materials are viable candidates for photonic crystal-based solar
      thermophotovoltaic devices and should be more extensively studied. 

PMID- 24129681
TI  - Antiphospholipid antibodies: neuropsychiatric presentations.
AB  - Antiphospholipid antibodies (aPL) are associated with a wide range of
      neurological, psychological, and psychiatric manifestations. In addition to
      clearly delineated purely thrombotic manifestations, which define the
      neurological contribution to the antiphospholipid syndrome, the strength of the
      other described associations is highly variable, and the underlying
      pathophysiological mechanisms are not fully understood. Some indications seem to
      support a psychiatric impact of aPL. The magnitude of the association and
      cellular and molecular mechanisms involved need to be further elucidated. 

PMID- 24129682
TI  - Cerebral venous thrombosis and thrombophilia: a systematic review and meta
      analysis.
AB  - Cerebral venous thrombosis (CVT) is a rare manifestation of venous
      thromboembolism (VTE) and stroke. The aim of our systematic review was to provide
      an updated summary of the strength of association between CVT and thrombophilia
      and to explore the relevance of thrombophilia for recurrence of CVT or other VTE,
      or other outcome variables. MEDLINE (via PubMed), EMBASE (via Ovid), and CENTRAL
      were systematically searched, including references of retrieved articles. Cohort
      studies of >= 40 patients and case-control studies comparing the prevalence of
      thrombophilia in patients with CVT and unrelated controls were eligible. Two
      reviewers independently selected studies, assessed quality, and extracted data. A
      meta-analysis was performed for high quality case-control studies with unselected
      cases and healthy controls. Odds ratios with 95% confidence intervals were
      calculated and pooled. We included 23 cohort studies and 33 case-control studies.
      A significant association was demonstrated between CVT and all inherited
      thrombophilic factors, as well as increased levels of homocysteine. Inconclusive
      results were found on the relevance of thrombophilia for recurrent CVT or other
      VTE. Although there is a strong association between CVT and thrombophilia, the
      clinical relevance of thrombophilia testing in patients with CVT seems limited,
      similarly to other forms of VTE. 

PMID- 24129683
TI  - Hypercoagulability, parkinsonism, and Gaucher disease.
AB  - Gaucher disease (GD) is a lysosomal disorder caused by inherited deficiency of
      glucocerebrosidase (GCase), resulting in the accumulation of glucocerebroside in
      macrophages, termed "Gaucher cells," leading to multiorgan involvement, with
      hepatosplenomegaly, cytopenias, pulmonary hypertension, and skeletal
      complications. Various mutations, encoding the GCase gene, cause acute or chronic
      neuronopathic forms of the disease. The hallmark of GD is the macrophages
      infiltrating organs, bone marrow, and nervous system compromising their function
      by inflammation, infarcts, fibrosis, and neuronal damage. Coagulation
      abnormalities are frequent among GD patients due to reduced production and
      chronic consumption of coagulation factors. Splenic and bone infarcts often occur
      in GD patients, but hypercoagulability is not frequent. Detection of
      thrombophilic risk factors in GD patients may predict a more severe course of the
      disease. Clinical and genetic studies revealed an association between reduced
      GCase activity in carriers of GD mutations and GD patients and occurrence of
      Parkinson disease (PD) and showed that GCase gene mutations are risk factors for
      PD development. The mechanisms underlying the association of PD and GD are not
      yet elucidated and should be further explored, particularly the potential
      involvement of inflammation and coagulation in the neurovascular unit. 

PMID- 24129684
TI  - The distinguishing cellular and molecular features of the endometriotic ovarian
      cyst: from pathophysiology to the potential endometrioma-mediated damage to the
      ovary.
AB  - BACKGROUND: Clinical data suggest that the presence of an ovarian endometrioma
      may cause per se damage to the surrounding otherwise healthy ovarian tissue.
      However, the basic research has so far done a limited job in trying to understand
      the potential detrimental effect of an endometrioma presence in the context of
      the ovarian physiology. We have reviewed the literature with the aim of
      characterizing the pathophysiology of the endometrioma focusing mostly on factors
      and mechanisms potentially affecting the surrounding, otherwise normal, ovarian
      tissue. METHODS: Comprehensive searches of PUBMED were conducted to identify
      human studies published from 1991 to 2013 in the English language on the cellular
      and molecular characterization of the various endometrioma components. RESULTS:
      An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic
      enzymes and inflammatory molecules in concentrations from tens to hundreds of
      times higher than those present in peripheral blood or in other types of benign
      cysts. The cyst fluid causes substantial changes in the endometriotic cells that
      it baths from gene expression modifications to genetic mutations The physical
      barrier between the cyst contents and the normal ovarian tissue is a thin wall
      composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially
      permeating the surrounding tissues and proteolytic substances degrading the
      adjacent areas are likely to cause the substitution of normal ovarian cortical
      tissue with fibrous tissue in which the cortex-specific stroma is reduced. The
      fibrosis is associated with smooth muscle metaplasia and followed by follicular
      loss and intraovarian vascular injury. Follicular density in tissue surrounding
      the endometriotic cyst was consistently shown to be significantly lower than in
      healthy ovaries but this pathological change does not appear to be caused by the
      stretching of surrounding tissues owing to the presence of a cyst. CONCLUSIONS:
      There is sufficient molecular, histological and morphological evidence, in part
      deriving from knowledge of the pathophysiology, to support a deleterious effect
      of the endometrioma on the adjacent ovarian cortical tissue, independent of the
      mere mechanical stretching owing to its size.

PMID- 24129686
TI  - Nonomuraea sp. ID06-A0189 inulin fructotransferase (DFA III-forming): gene
      cloning, characterization and conservation among other Nonomuraea species.
AB  - The inulin fructotransferase (DFA III-forming)(EC 4.2.2.18) gene in Nonomuraea
      sp. ID06-A0189 was amplified from genomic DNA, sequenced and expressed in
      Escherichia coli. The 1326-bp gene, designated as Nsp-ift, encodes a protein
      composed of a putative 37-amino-acid signal peptide and 404-amino-acid mature
      protein. A putative ribosomal binding sequence was identified 12 bases upstream
      from the start codon. However, a typical bacterial promoter could not be found by
      in silico analysis. The deduced amino-acid sequence of the enzyme was most
      similar to that of inulin fructotransferase (DFA I-forming) in Frankia sp.
      EAN1pec. Phylogenetic analysis of deduced amino-acid sequences indicated that
      Nonomuraea sp. ID06-A0189 and Frankia sp. EAN1pec inulin fructotransferases
      formed a distinct clade from those from Arthrobacter sp. H65-7, A. globiformis
      and Bacillus sp. snu-7 that showed 57, 56 and 56% identity to that of Nsp-ift,
      respectively. The Nsp-ift without a putative signal peptide was successfully
      expressed in E. coli and partially purified using His-tag affinity
      chromatography. The recombinant enzyme displayed optimum temperature between 65
      and 70  degrees C, optimum pH between 5.5 and 6.0 and remained stable up to 70 
      degrees C. The properties were identical to those of the original enzyme. Of 10
      Nonomuraea species tested by Southern hybridization, enzyme activity measurements
      and PCR, only Nonomuraea sp. ID06-A0189 has the Nsp-ift gene, suggesting that Nsp
      ift is not highly conserved in this genus. 

PMID- 24129687
TI  - Functional analysis of hatomarubigin biosynthesis genes and production of a new
      hatomarubigin using a heterologous expression system.
AB  - The function of hatomarubigin biosynthesis genes was analyzed by heterologous
      expression of the hrb gene cluster. Streptomyces lividans carrying a gene cluster
      consisting of 25 genes (hrbR1-hrbX) with hrbY was found to produce all the known
      hatomarubigins including hatomarubigin D, which has a unique dimeric angucycline
      with a methylene linkage. Gene disruption was used in this heterologous
      expression system to analyze the function of hrbF, a gene with no homology to any
      known angucycline biosynthesis genes. A new metabolite was detected in the
      fermented broth of S. lividans expressing the hrb genes lacking hrbF and was
      designated hatomarubigin F. This compound was identified as 5
      hydroxyhatomarubigin E by NMR spectroscopic analysis, suggesting that HrbF
      regulates the regiospecificity of oxygenation enzymes. 

PMID- 24129688
TI  - Milestones in cardiovascular medicine: 10 or more?

PMID- 24129689
TI  - Atrial fibrillation: to map or not to map?
AB  - Isolation of the pulmonary veins may be an effective treatment modality for
      eliminating atrial fibrillation (AF) episodes but unfortunately not for all
      patients. When ablative therapy fails, it is assumed that AF has progressed from
      a trigger-driven to a substrate-mediated arrhythmia. The effect of radiofrequency
      ablation on persistent AF can be attributed to various mechanisms, including
      elimination of the trigger, modification of the arrhythmogenic substrate,
      interruption of crucial pathways of conduction, atrial debulking, or atrial
      denervation. This review discusses the possible effects of pulmonary vein
      isolation on the fibrillatory process and the necessity of cardiac mapping in
      order to comprehend the mechanisms of AF in the individual patient and to select
      the optimal treatment modality. 

PMID- 24129690
TI  - Chiroptical properties, binding affinity, and photostability of a conjugated zinc
      porphyrin dimer complexed with left-handed Z-DNA and right-handed B-DNA.
AB  - We have studied the UV-vis absorption and chiroptical properties, binding
      affinity and photostability of a conjugated positively charged butadiyne-linked
      Zn(ii) porphyrin dimer bound to DNA sequence poly(dG-dC)2. Right-handed B-DNA,
      spermine-induced Z-DNA and Co(iii)-induced Z-DNA have been explored. Resonance
      light scattering (RLS) spectra showed formation of porphyrin aggregates in the
      presence of all DNA forms with the largest aggregates formed with B-DNA. The
      porphyrin dimer gave rise to induced bisignate circular dichroism (CD) signals in
      the presence of the left-handed Z-DNA conformations. On the other hand, the dimer
      stayed nearly chiroptically silent when complexed with the B-form of poly(dG
      dC)2. Our results indicated that the conjugated Zn(ii) porphyrin dimer can be
      used as a sensor for the chiroptical detection of Z-DNA in the visible (400-500
      nm) and near-infrared region of the electromagnetic spectrum (700-800 nm). The
      helicity of DNA had little effect on the dimer binding affinities. The
      photostability of the porphyrin dimer complexed with any form of DNA was higher
      than that of the free molecule. The porphyrin dimer bound to Z-DNA exhibited
      slower photobleaching than the B-DNA dimer complex. 

PMID- 24129691
TI  - Pharmacokinetics and toxicity of intrathecal liposomal cytarabine in children and
      adolescents following age-adapted dosing.
AB  - BACKGROUND AND OBJECTIVE: Assessment of the optimal drug dose for intrathecal
      therapy in children is challenging because of the non-linear increase in
      cerebrospinal fluid (CSF) volume throughout childhood and potential differences
      in the elimination rate in children versus adults. The present study was designed
      to prospectively collect pharmacokinetic and safety data on age-adapted
      intrathecal liposomal cytarabine in children aged >3 years. PATIENTS AND METHODS:
      Sixteen patients with malignant brain tumours were included in the study.
      Children aged 3-10 years received liposomal cytarabine 35 mg with concomitant
      dexamethasone, and those aged >10 years received 50 mg. Serial CSF and plasma
      samples were collected before administration and 1 h, 12 h, 24 h, 1 week and 2
      weeks post-dosing. CSF was analysed for free and encapsulated cytarabine, and
      plasma was analysed for free cytarabine. RESULTS: The average elimination half
      life values in children aged 3-10 years and in those aged >10 years, treated with
      liposomal cytarabine 35 mg and 50 mg, respectively, were 40.9 and 43.7 h for free
      cytarabine and 31.5 and 36.4 h for encapsulated cytarabine in CSF. Although these
      values were lower than those previously reported, cytarabine concentrations
      exceeded the cytotoxic threshold of 0.1 mg/L in all patients until 1 week post
      intraventricular administration. Cytarabine concentrations in plasma were
      negligible. In general, liposomal cytarabine was well tolerated, with relevant
      but manageable toxicities. CONCLUSION: Liposomal cytarabine in doses of 35 mg for
      children aged 3-10 years and 50 mg for older patients shows sufficient drug
      exposure for at least 1 week and appears to be well tolerated.

PMID- 24129693
TI  - Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our
      experience.
AB  - Invasion of the laryngeal framework by thyroid carcinoma requires specific
      surgical techniques and carries a higher rate of complications that deserve to be
      highlighted. We reviewed our data from 1995 to 2012 and found six patients with
      laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy
      and single-stage cricotracheal resection, plus anterolateral neck dissection.
      Three had airway obstruction that necessitated prior endoscopic debulking. None
      of the patients needed a tracheotomy. There were four cases of papillary
      carcinoma, and two cases of undifferentiated carcinoma. One patient died of
      complications of the procedure (anastomotic dehiscence and tracheo-innominate
      artery fistula). Another died 2 months after the procedure from local recurrence
      and aspiration pneumonia. One case presented recurrence at 15 months, which was
      managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up,
      he has no evidence of locoregional recurrence. The three other patients are alive
      without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal
      resection for subglottic invasion by thyroid carcinoma is an effective procedure,
      but carries significant risks of complications. This could be attributed to the
      devascularisation of the tracheal wall due to the simultaneous neck dissection,
      sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We
      advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal
      resection for subglottic invasion can be curative with good functional outcomes,
      even for the advanced stages of thyroid cancer. Endoscopic debulking of the
      airway prior to the procedure avoids tracheotomy.

PMID- 24129695
TI  - Relevance of tricuspid annular peak systolic velocity (s') to detect systolic
      right-ventricular impairment after anthracycline cancer treatment in childhood.

PMID- 24129694
TI  - A new grafting technique for tympanoplasty: tympanoplasty with a boomerang-shaped
      chondroperichondrial graft (TwBSCPG).
AB  - The aim of this study was to introduce a new grafting technique in tympanoplasty
      that involves use of a boomerang-shaped chondroperichondrial graft (BSCPG). The
      anatomical and functional results were evaluated. A new tympanoplasty with
      boomerang-shaped chondroperichondrial graft (TwBSCPG) technique was used in 99
      chronic otitis media patients with central or marginal perforation of the
      tympanic membrane and a normal middle ear mucosa. All 99 patients received
      chondroperichondrial cartilage grafts with a boomerang-shaped cartilage island
      left at the anterior and inferior parts. Postoperative follow-ups were conducted
      at months 1, 6, and 12. Preoperative and postoperative audiological examinations
      were performed and air-bone gaps were calculated according to the pure-tone
      averages (PTAs) of the patients. In the preoperative period, most (83.8%) air
      bone gaps were >= 16 dB; after operating using the TwBSCPG technique, the air
      bone gaps decreased to 0-10 dB in most patients (77.8%). In the TwBSCPG patients,
      the mean preoperative air-bone gap was 22.02 +/- 6.74 dB SPL. Postoperatively,
      the mean postoperative air-bone gap was 8.70 +/- 5.74 dB SPL. The TwBSCPG
      technique therefore decreased the postoperative air-bone gap compared to that
      preoperatively (p = 0.000, z = -8.645). At the 1-month follow-up, there were six
      graft perforations and one graft retraction. At the 6-month follow-up, there were
      nine graft perforations and three graft retractions. At 12 months, there were
      seven graft perforations and four graft retractions. During the first year after
      the boomerang tympanoplasty surgery, graft lateralization was not detected in any
      patient. Retractions were grade 1 according to the Sade classification and were
      localized to the postero-superior quadrant of the tympanic membrane. The TwBSCPG
      technique has benefits with respect to postoperative anatomical and audiological
      results. It prevents perforation of the tympanic membrane at the anterior
      quadrant and avoids graft lateralization due to placement of the graft under the
      manubrium mallei. Given these benefits, the TwBSCPG technique seems to be a good
      alternative for grafting in tympanoplasties.

PMID- 24129696
TI  - Indentification of huperzine A-producing endophytic fungi isolated from Huperzia
      serrata.
AB  - This present study was designed to investigate the production of huperzine A
      (HupA), an acetylcholine inhibitor, which was produced by an endophytic fungi
      isolated from Huperzia serrata. Screening of 94 endophytic fungal isolates
      obtained from plant H. serrata was carried out for the production of HupA. Their
      morphological characteristics were studied and rDNA sequence analysis was carried
      out. The cultures were grown in liquid culture medium and the extracted
      metabolites were analyzed by thin layer chromatography and high performance
      liquid chromatograph for the presence of HupA. The DPPH scavenging ratio and
      inhibition ratio of acetylcholinesterase (AchE) of the same were determined. 3
      out of 94 strains i.e. S29, L44 and S94 showed significant AchE-inhibitory
      activity and antioxidant activity. Strain L44 which exhibited maximum yield of
      HupA (37.63 MUg/g on dry weight basis) was identified as Trichoderma species by
      ITS sequence analysis. In conclusion, endophytic fungi from H. serrata can be
      used as a new resource of HupA. 

PMID- 24129697
TI  - Comparative physiological study of the wild type and the small colony variant of
      Pseudomonas aeruginosa 20265 under controlled growth conditions.
AB  - Small-colony variants (SCVs) of Pseudomonas aeruginosa are often found in
      chronically infected airways of patients suffering from cystic fibrosis. These
      slow-growing morphological variants have been associated with persistent and
      antibiotic-resistant infections. Nevertheless, the behavior of SCVs under varied
      availability of O2 and iron, two key variables relevant to the lung environment
      of CF patients and pathogenicity of P. aeruginosa, has not been systematically
      studied so far. In this work, the effects of O2 and iron were comparatively
      studied for a CF P. aeruginosa wild type (WT) strain and its SCV phenotype in a
      real-time controlled cultivation system. Significant differences in the behavior
      of these strains were observed and quantified. In general, SCV exhibited a higher
      fitness than the WT toward aerobic conditions. Under iron rich condition, and
      despite less release of total extracellular proteins, absence of flagellin and
      lower siderophore production, the SCV cells grown at fully aerobic conditions
      showed a higher specific growth rate and a significantly higher cytotoxicity in
      comparison with the WT cells. The strains behaved also differently towards iron
      limitation. The phenomena of limited O2 transfer from the gas to the liquid phase
      and enhancement of formation of virulence factors under conditions of iron
      limitation were much more profound in the SCV culture than in the WT culture.
      These results have important implications for better understanding the
      pathogenicity of P. aeruginosa and its small-colony variants.

PMID- 24129698
TI  - Molecular phylogenetic analysis of dominant microbial populations in aged refuse.
AB  - The phylogenetic analysis of dominant microbial populations in 8-year-old refuse
      samples was done in terms of the whole Bacterial and Archaeal domains. The
      results indicated that the Bacterial 16S rRNA genes sequences from the aged
      refuse were largely affiliated with the genus Bacillus, and that more than 60 %
      of the Archaeal sequences were closely related to the methanogenic archaeon. Some
      inferentially identified extremophilic organisms, particularly alkaliphiles
      and/or halophiles, were noted to be present in the aged refuse. Moreover,
      molecular evidence for the occurrence of ammonia-oxidizing Archaea in aged refuse
      was reported, which opens up avenues for elucidating its role in ammonia
      transformation in landfill systems. It seems reasonable to assume that the highly
      complex environment within the landfill systems may select for microbial
      populations with versatile metabolism and strong adaptation. These findings
      underline the need for further biochemical and ecological study of these
      organisms in aged refuse. 

PMID- 24129699
TI  - Too fast to die.
AB  - Signals generated by the T cell receptor (TCR) result in the death or survival of
      developing thymocytes (T cell precursors), depending on the affinity of the TCR
      for peptide ligands bound to the major histocompatibility complex (MHC) that are
      encountered in the thymus. A new study by Ellen Robey's group in this issue of
      Science Signaling presents a systematic evaluation of signaling and motility
      changes in thymocytes that encounter ligands of different affinities in the
      thymic environment. In contrast to previous in vitro studies, the authors found
      that low-affinity ligands stimulated infrequent transient mobilization of
      intracellular Ca(2+), whereas high-affinity ligands triggered sustained Ca(2+)
      signaling and periods of migratory arrest. For ligands of intermediate affinity,
      changes in thymocyte motility, rather than in Ca(2+) signaling patterns, provided
      the best correlation with functional outcomes. These findings suggest that
      transient signaling events in the absence of strong stop signals are required for
      thymocyte survival and functional maturation in the thymus. 

PMID- 24129700
TI  - Using functional signature ontology (FUSION) to identify mechanisms of action for
      natural products.
AB  - A challenge for biomedical research is the development of pharmaceuticals that
      appropriately target disease mechanisms. Natural products can be a rich source of
      bioactive chemicals for medicinal applications but can act through unknown
      mechanisms and can be difficult to produce or obtain. To address these
      challenges, we developed a new marine-derived, renewable natural products
      resource and a method for linking bioactive derivatives of this library to the
      proteins and biological processes that they target in cells. We used cell-based
      screening and computational analysis to match gene expression signatures produced
      by natural products to those produced by small interfering RNA (siRNA) and
      synthetic microRNA (miRNA) libraries. With this strategy, we matched proteins and
      miRNAs with diverse biological processes and also identified putative protein
      targets and mechanisms of action for several previously undescribed marine
      derived natural products. We confirmed mechanistic relationships for selected
      siRNAs, miRNAs, and compounds with functional roles in autophagy, chemotaxis
      mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus,
      this approach may be an effective method for screening new drugs while
      simultaneously identifying their targets. 

PMID- 24129701
TI  - Diacylglycerol kinase zeta limits B cell antigen receptor-dependent activation of
      ERK signaling to inhibit early antibody responses.
AB  - Signaling downstream of the B cell antigen receptor (BCR) is tightly regulated to
      enable cells to gauge the strength and duration of antigen-receptor interactions
      and to respond appropriately. We investigated whether metabolism of the second
      messenger diacylglycerol (DAG) by members of the family of DAG kinases (DGKs)
      played a role in modulating the magnitude of signaling by DAG downstream of the
      BCR. In the absence of DGKzeta, the threshold for BCR signaling, measured as
      activation of the Ras-extracellular signal-regulated kinase (ERK) pathway, was
      markedly reduced in mature follicular B cells, which resulted in enhanced
      responses to antigen in vitro and in vivo. Inhibition of DAG signaling by DGKzeta
      limited the number of antibody-secreting cells that were generated early in
      response to T cell-independent type 2 antigens, as well as to T cell-dependent
      antigens. Furthermore, the effect of loss of DGKzeta closely resembled the effect
      of increasing the affinity of the BCR for antigen during the T cell-dependent
      antibody response. These results suggest that the magnitude of DAG signaling is
      important for translating the affinity of the BCR for antigen into the amount of
      antibody produced during the early stages of an immune response. 

PMID- 24129703
TI  - Disagreement over vaccination programmes: deep or merely complex and why does it
      matter?
AB  - This paper argues that significant aspects of the vaccination debate are 'deep'
      in a sense described by Robert Fogelin and others. Some commentators have
      suggested that such disagreements warrant rather threatening responses. I argue
      that appreciating that a disagreement is deep might have positive implications,
      changing our moral assessment of individuals and their decisions, shedding light
      on the limits of the obligation to give and respond to arguments in cases of
      moral disagreement, and providing an incentive to seek alternative ways of going
      on in the face of intractable moral disagreement. Non-coercive, non-reasoned
      strategies have been used or recommended to increase vaccination rates. Such
      strategies look problematic when judged by the standards of ideal moral and
      rational argumentation, but more acceptable if seen as responses to deep
      disagreements. 

PMID- 24129702
TI  - Distinct temporal patterns of T cell receptor signaling during positive versus
      negative selection in situ.
AB  - The recognition by the T cell receptor (TCR) of self-peptides presented by the
      major histocompatibility complex (MHC) on antigen-presenting cells, such as
      dendritic cells and thymic epithelial cells, controls T cell fate in the thymus,
      with weak TCR signals inducing survival (positive selection) and stronger signals
      inducing death (negative selection). In vitro studies indicate that peptide
      ligands that induce positive selection stimulate a low, but sustained, pattern of
      TCR signaling; however, the temporal pattern of TCR signaling in MHC class I
      restricted thymocytes (thymocytes that are presented with peptides by MHC class
      I) in the thymus, under conditions that support positive selection, is unknown.
      We addressed this question by examining intracellular Ca(2+) dynamics and
      migratory changes in thymocytes undergoing positive and negative selection in
      thymic slices. Brief, serial signaling events that were separated by migratory
      periods and low cytosolic Ca(2+) concentrations correlated with the positive
      selection of MHC class I-restricted thymocytes, whereas sustained Ca(2+)
      signaling and the arrest of thymocytes were associated with negative selection.
      Low-avidity peptides and the presentation of peptides by cortical thymic
      epithelial cells, rather than dendritic cells, failed to induce strong migratory
      arrest of thymocytes, which led to transient TCR signaling. Thus, we provide a
      comparison of positive and negative selection signals in situ and suggest that
      the absence of strong stop signals distinguishes between positive and negative
      selection. 

PMID- 24129704
TI  - Analysis of functional redundancies within the Arabidopsis TCP transcription
      factor family.
AB  - Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL
      FACTOR1 (TCP) transcription factors have been hampered by functional redundancy
      between its individual members. In general, putative functionally redundant genes
      are predicted based on sequence similarity and confirmed by genetic analysis. In
      the TCP family, however, identification is impeded by relatively low overall
      sequence similarity. In a search for functionally redundant TCP pairs that
      control Arabidopsis leaf development, this work performed an integrative
      bioinformatics analysis, combining protein sequence similarities, gene expression
      data, and results of pair-wise protein-protein interaction studies for the 24
      members of the Arabidopsis TCP transcription factor family. For this, the work
      completed any lacking gene expression and protein-protein interaction data
      experimentally and then performed a comprehensive prediction of potential
      functional redundant TCP pairs. Subsequently, redundant functions could be
      confirmed for selected predicted TCP pairs by genetic and molecular analyses. It
      is demonstrated that the previously uncharacterized class I TCP19 gene plays a
      role in the control of leaf senescence in a redundant fashion with TCP20.
      Altogether, this work shows the power of combining classical genetic and
      molecular approaches with bioinformatics predictions to unravel functional
      redundancies in the TCP transcription factor family. 

PMID- 24129705
TI  - Computed tomography and sectional anatomy of the head cavities in donkey (Equus
      asinus).
AB  - The purpose of this study was to describe the computed tomographic (CT) anatomy
      of normal donkey head cavities to be used as a basis for interpretation of CT
      images of donkey. Six adult donkeys' heads of undetermined sex were used in this
      study. The donkey heads were divided into three regions-nasal, orbital, and
      cranial-to show the morphology of the following cavities: nasal cavity, paranasal
      sinuses, orbital cavity, oral cavity, pharyngeal cavity, especially the guttural
      pouch, cranial cavity and temporomandibular joint. The donkey head had six pairs
      of sinuses: three paranasal (the frontal, maxillary and sphenopalatine sinuses)
      and three nasal (dorsal, middle and ventral conchal) sinuses. The maxillary sinus
      was subdivided into rostral and caudal compartments by a thin incomplete bony
      septum that was identified and labeled according to cheek teeth landmarks. The
      topographic description and relationship between the nasal, oral, orbital,
      cranial, temporomandibular joint, pharyngeal cavities and paranasal sinuses were
      demonstrated. The articular disc, articular surface and joint capsule of the
      temporomandibular joint were indicated easily in our CT and cross sectional
      images. 

PMID- 24129707
TI  - Utility of eosinophil cationic protein levels in the diagnosis of intrinsic
      atopic dermatitis.

PMID- 24129706
TI  - Screening for bladder cancer with urinary tumor markers in chemical workers with
      exposure to aromatic amines.
AB  - PURPOSE: To validate urinary markers for the early detection of bladder cancer
      (BC) in chemical workers. METHODS: UroScreen was conducted as a validation study
      for tumor markers within the frame of a health surveillance program of the German
      Social Accident Insurance for active or retired workers with former exposure to
      aromatic amines. From 2003 to 2010, 1,609 men took part in voluntary annual
      screens. Cytology, the quantitative NMP22((r)) assay, and UroVysionTM were
      applied to 7,091 urine samples. RESULTS: Fifteen out of 21 tumors were detected
      following test positivity. The UroVysion/NMP22 panel detected 14 out of 21 tumors
      versus 8 tumors with cytology alone (sensitivity 66.7 vs. 44.4 %, specificity
      94.5 vs. 98.5 %). The sensitivity of the panel increased to 85.7 % in samples
      collected <=12 months before diagnosis and when papillomas were excluded,
      compared to 58.3 % with cytology. About 3 % of NMP22 tests were false-positive.
      UroVysion results overlapped with cytology due to the preselection of atypical
      cells. NMP22 was less and UroVysion more frequently positive in diluted urine
      samples. Leukocytes confounded NMP22 but not UroVysion. The low incidence of BC
      in this study population yielded low positive predictive values of the markers
      and high costs per tumor detected with screening. CONCLUSIONS: UroVysion in
      combination with NMP22 detected more cases than cytology alone, at the expense of
      a lower specificity. High costs per detected case resulted from a lower BC
      incidence than in the past when levels of occupational exposure to aromatic
      amines were higher. Currently, it cannot be recommended to apply these markers
      for screening in asymptomatic workers. The increase in sensitivity is not
      balanced by the high costs of UroVysion and the false-positive tests of NMP22.

PMID- 24129708
TI  - Unprecedented and highly symmetric (6,8)-connected topology in a porous metal
      organic framework through a Zn-Ti heterometallic approach.
AB  - The Zn(II)-Ti(IV) heterometallic approach is successfully adopted to produce a
      highly symmetric, binodal metal-organic framework with unprecedented topology in
      network solids. This material, ZTOF-2, possesses permanent porosity as shown by
      reversible sorption of various gases.

PMID- 24129709
TI  - Cross-talk between KLF4 and STAT3 regulates axon regeneration.
AB  - Cytokine-induced activation of signal transducer and activator of transcription 3
      (STAT3) promotes the regrowth of damaged axons in the adult central nervous
      system (CNS). Here we show that KLF4 physically interacts with STAT3 upon
      cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This
      interaction suppresses STAT3-dependent gene expression by blocking its DNA
      binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult
      retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This
      regeneration can be greatly enhanced by exogenous cytokine treatment, or removal
      of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine
      signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4
      and activated STAT3 in the regulation of axon regeneration that might have
      therapeutic implications in promoting repair of injured adult CNS. 

PMID- 24129710
TI  - (11)C-acetate as a new biomarker for PET/CT in patients with multiple myeloma:
      initial staging and postinduction response assessment.
AB  - PURPOSE: We investigated the potential value of (11)C-acetate (ACT) PET/CT in
      characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT. Bone marrow
      histological and whole-body (WB) MRI findings served as the reference standards.
      METHODS: In this prospective study, 15 untreated MM patients (10 men and 5 women,
      age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and
      WB MRI for pretreatment staging, and 13 of them had repeated examinations after
      induction therapy. Diffuse and focal bone marrow uptake was assessed by visual
      and quantitative analyses, including measurement of the maximum standardized
      uptake value (SUVmax). Between-group differences and correlations were assessed
      with the Mann-Whitney U test and the Pearson test. RESULTS: At staging, all 15
      patients had diffuse myeloma involvement upon bone marrow examination with 30-90
      % of plasma cell infiltrates. Diffuse infiltration was detected in all of them
      (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake
      values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In
      contrast, a diagnosis of diffuse infiltration could be established using (18)F
      FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both
      (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal
      lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 +/- 3.3 (range
      4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean
      SUVmax 6.6 +/- 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse
      bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients
      with at least a very good partial response versus 34 % in those with at most a
      partial response only (p=0.01). CONCLUSION: PET/CT using (11)C-ACT as a biomarker
      showed a higher detection rate for both diffuse and focal myeloma lesions at
      diagnosis than using (18)F-FDG, and may be valuable for response assessment.

PMID- 24129711
TI  - Abstracts of the Annual Congress of the European Association of Nuclear Medicine.
      October 10-9-23, 2013. Lyon, France.

PMID- 24129712
TI  - [Editorial].

PMID- 24129713
TI  - [Intramedullary stabilisation of clavicula fractures].
AB  - With an incidence of 64/100,000, clavicular shaft fractures are one of the most
      common fractures. Intramedullary fixation with Prevot nails was initially
      reported in the late 1990s. This procedure offers minimally invasive
      stabilization of the fracture, thus enabling immediate mobilization and rapid
      loading capacity. Using a case study, the positioning and procedure are
      demonstrated on video. The intramedullary implant accommodates the varying
      tension loading of the clavicle. This treatment is ideal for clavicular fractures
      with 2-3 fragments. Compared to patients treated conservatively, operated
      patients achieve more rapid and improved mobility. Employment disability is
      shorter, and malunion occurs less frequently. 

PMID- 24129714
TI  - [Videos in the Journal of Orthopaedics and Traumatology -- a new section].

PMID- 24129715
TI  - [A rare complication of kyphoplasty is PMMA-cement loosening - case report and
      literature review].
AB  - INTRODUCTION: For vertebral body fractures combined with strong back pain, the
      kyphoplasty is an established method for pain reduction. A balloon effects an
      excavation in the vertebral body, which will be filled up with cement. We
      distinguish between cements of polymethyl metacrylate (PMMA) and calcium
      phosphate. Their diverse chemical qualities enable different indications. CASE
      REPORT: A 72-year-old male patient with refractory back pain after a lumbar
      vertebral body fracture was treated with a kyphoplasty operation. After four days
      the patient went home with clearly less pain. After two months the patient had a
      bagatelle trauma at home, which caused an exacerbation of the back pain. In
      computered tomography we saw a disruption of the PMMA cement plombage forwards
      and also a kyphosis of the lumbar vertebrae. Therefore we had to operate on the
      patient two more times. The first time we stabilised the spine from dorsal via an
      internal fixator. The additive ventral fixation was at that time declined by the
      patient. Because of the persistency of the back pain after operation combined
      with a sense of instability, we were ten days after the first revision allowed to
      stabilise the patient from ventrally with a Harms cage. At the first-year follow
      up the patient was still free of pain. CONCLUSION: Injuries of the vertebral body
      frame cannot be operated exclusively with kyphoplasty. The reason for this is the
      instability of the vertebral body despite the injection of the PMMA cement. We
      advise to stabilise the spine in such cases with a dorsal internal fixator
      additively.

PMID- 24129716
TI  - [Effect of continuous passive motion for cartilage regenerative surgery - a
      systematic literature review].
AB  - BACKGROUND: The aim of this systematic review was to evaluate treatment effects
      of continuous passive motion (CPM) after surgical cartilage repair.
      PATIENTS/MATERIAL AND METHODS: A literature search was conducted in the Cochrane
      Central Register of Controlled Trials, EMBASE, International Clinical Trials
      Registry Platform, MEDLINE, Trip Database and in bibliographies of included
      studies. Two independent researchers evaluated the quality of original
      investigations by the Cochrane Risk of Bias tool. Systematic reviews were checked
      by the CBO/Dutch Cochrane Centre Guideline. RESULTS: A total of 1541 studies was
      initially retrieved from the databases. After screening for inclusion criteria,
      one review and ten original papers could be included for further evaluation.
      Studies showed methodological weaknesses. Heterogeneity of outcome measures and
      the fact that 6 of 9 studies with an one-group pre-post design measured the
      combined effect of surgical treatment and CPM prevented a meta-analysis.
      CONCLUSION: Three studies described significant improvements with regard to
      subjective outcome such as pain, swelling, Quality Life Survey, Knee Society
      score, WOMAC score or rating Cincinnati due to the surgical treatment and the CPM
      intervention of cartilage defects in the knee. Six (case) studies suggested an
      enhanced cartilage quality of the patients after CPM. More high-quality
      randomised controlled trials are needed to provide high level evidence.

PMID- 24129717
TI  - [Treatment of extensor mechanism rupture after total knee arthroplasty].
AB  - Disruption of the extensor mechanism is one of the most devastating complications
      in knee arthroplasty with a reported incidence between 0.17 and 2.5 %. Due to a
      high rate of subsequent complications and poor clinical results, every effort
      should be made to avoid extensor mechanism disruption. In cases of disruption
      however, the orthopaedic surgeons must be aware of non-operative and surgical
      treatment options and their indications, timing, outcome and limitations. Non
      operative treatment is feasible in cases of incomplete disruption of the
      quadriceps tendon with an extension deficit of less than 20 degrees . Complete
      disruption of the quadriceps tendon or rupture of the patellar tendon should be
      treated operatively. Therapeutic strategies include direct repair of the tendon
      in acute disruption without retraction. Retraction as well as soft tissue damage
      necessitates augmentation of the tendon. Frequently used endogenous augments are
      the semitendinosus tendon as well as the gastrocnemius muscle. Exogenous options
      are allografts of the Achilles tendon or structured extensor mechanism grafts and
      synthetic augments to support endogenous tendon repair. The clinical results
      after extensor mechanism failure following total knee arthroplasty are less
      favourable compared to ruptures in native knee joints. The most common
      complications are postoperative stretching and the maintenance of an active
      extensor lag. 

PMID- 24129718
TI  - [Minimally invasive surgery for knee total arthroplasty - evidence-based
      advantages?].
AB  - The impact of minimally invasive surgical techniques for implantation of a total
      knee arthroplasty is evaluated according to evidence-based medicine criteria. The
      patient-relevant clinical question can be formulated as: Is the rehabilitation of
      osteoarthritis patients with minimally invasive implantation of total knee
      arthroplasty faster compared to those with the conventional approach. The
      available literature is sorted and critically appraised with regard to
      methodological quality and risk of bias. Following the results of the meta
      analyses the clinical question can be positively answered. Following the aspect
      of a structured evolution for surgical techniques, the meaning of a minimally
      invasive technique for total knee arthroplasty cannot be answered finally. Under
      the impression of more frequent surgical complications, the rating of the
      procedure is conservative. A general advantage is not apparent. Further studies
      investigating surgical learning curves, proper patient selection and the
      selection of the patient for such techniques are required, before the final
      judgement on the use of this technique can be formed. 

PMID- 24129719
TI  - [Flap coverage of soft tissue defects after total knee arthroplasty].
AB  - Due to the marginal periarticular soft tissue envelope and the high risk of
      concomitant soft tissue or periprosthetic infection with the presence of exposed
      metal or bone, soft tissue defects after total knee arthroplasty are always a
      relevant surgical problem. Specific patient-related, intra- and postoperative
      risk factors have been identified and need to be considered during the course of
      treatment. Often a profound management of underlying infection must accompany the
      staged defect treatment which could require a prosthesis explantation with
      secondary revision in the case of a deep infection and involvement of the
      prosthesis. Four stages of soft tissue defects have been introduced (types A-D)
      and criteria for differentiation are the overall soft tissue coverage, the
      exposure, respectively, necrosis of the extensor mechanism, preservation or
      involvement of the joint capsule and/or an accompanying septic loosening of the
      prosthesis. The concept of plastic coverage follows a stage-adapted algorithm and
      includes secondary wound healing and mesh coverage for superficial defects,
      fasciocutaneous flaps for moderate defects and pedicled or free muscle flaps for
      deep defect situations with extension into the joint capsule. Crucial factors for
      a successful therapy include the early identification and precise analysis of
      defect characteristics, the careful preparation of the wound bed with serial
      debridements and the diligent flap coverage with early consultation of plastic
      surgical expertise. 

PMID- 24129720
TI  - [Anatomic reconstruction of hip joint biomechanics with the bone preserving
      Silent Micro HipTM prosthesis].
AB  - BACKGROUND: The design and the surgical technique of the Silent Micro HipTM are
      different compared to other hip stems due to a conical shape for fixation within
      the metaphyseal femur. The purpose of the present study was to evaluate hip joint
      biomechanics of the Silent Micro HipTM in comparison to other implants. Implant
      specific differences are highlighted. MATERIAL AND METHOD: 150 consecutive
      patients (each group 50 Silent Micro HipTM, NanosTM and SL-PlusTM MIA) were
      analysed retrospectively. For evaluation of biomechanical parameters pre- and
      postoperative X-rays (pelvic AP views) were used. RESULTS: The horizontal femoral
      offset and the limb length showed no significant difference between the Silent
      Micro HipTM and the NanosTM or SL-PlusTM MIA stem at the reconstructed hip. An
      almost anatomic reconstruction of hip joint biomechanics was reached with all
      three types of implants. CONCLUSIONS: The Silent Micro HipTM allows for almost
      anatomic reconstruction of hip joint biomechanics. Short-term results support the
      bone-preserving reconstruction with a proximal femoral load transfer. Further
      studies on the mid- and long-term outcomes are ongoing.

PMID- 24129721
TI  - [Psoas haematoma due to irritation of the psoas tendon].
AB  - Irritation of the tendon of the musculus iliopsoas after total hip replacement is
      a rare complication. In connection with the irritation of the iliopsoas tendon
      only one case report of a psoas haematoma due to anticoagulation has been
      published. We assume that these kinds of haematomas are more frequent than
      described. We report on 2 cases of haematoma caused by an iliopsoas impingement
      after total hip replacement. In one case a lesion of the femoral nerve was
      observed. Surgical treatment was composed of the revision of the acetabular
      component. 

PMID- 24129722
TI  - [Interpositional arthrodesis of the first metatarsophalangeal joint].
AB  - BACKGROUND: Interpositional arthrodesis of the first metatarsophalangeal joint is
      a rare procedure which is indicated for reconstruction of an insufficient, short
      first ray due to loosening of an endoprosthesis, osteomyelitis or after a Keller
      procedure. PATIENTS AND METHODS: In a retrospective study we evaluated the
      outcome of 15 patients with a mean age of 62 years, who underwent an
      interpositional arthrodesis of the first MTP joint. Correction of the deformity
      was achieved by osteotomy of the tricortical bone graft. Osteosynthesis was
      performed by use of screw fixation alone or by combined screw, plate and K-wire
      fixation. Postoperatively patients were mobilised for 10 weeks in a forefoot off
      loading shoe. Clinical and radiological examination was performed 10 weeks
      postoperatively. Radiological parameters such as hallux valgus angle, MTP
      dorsiflexion angle and the graft size were measured. In all patients pre- and
      postoperatively, the intensity of pain (VAS), the overall satisfaction with the
      procedure and the American orthopaedic foot and ankle score (AOFAS score) were
      evaluated. RESULTS: The mean follow-up was 26 months (range 4-48 months). The
      mean pain intensity measured with the VAS was reduced from 7.5 preoperatively to
      0.5 postoperatively. In 14 patients fusion of the arthrodesis was achieved at a
      mean of 12 weeks. One patient developed a pseudarthrosis which was effectively
      treated by extracorporeal shockwaves. Postoperatively radiological measurements
      demonstrated a mean hallux valgus angle of 16 degrees  (range 6-28 degrees ), a
      mean MTP dorsiflexion angle of 17 degrees  (range 12-27 degrees ) and a mean
      graft size of 16 mm (range 10-30 mm). The mean AOFAS score improved from 26
      preoperatively to 81 postoperatively. All but 1 patient were satisfied with the
      final outcome and achieved free mobility. CONCLUSIONS: Interpositional
      arthrodesis of the first MTP joint achieves good clinical and radiological
      results with a high level of patient satisfaction in patients with an
      insufficient and short first ray of the foot.

PMID- 24129723
TI  - [Evidence-based treatment of combined rotator cuff and SLAP lesions].
AB  - PURPOSE: In the face of improved radiological and arthroscopic techniques the
      diagnosis and treatment of SLAP lesions has recently gained much interest.
      Originally described as an (isolated) injury of the overhead athlete, it was only
      recently that the association of SLAP and rotator cuff defects was described in
      up to 40 % of cases. This study addresses the question of the evidence-based
      treatment of such frequent, combined lesions. METHODS: Based on a systematic
      review of the online databases PubMed, EMBASE, CINAHL and Cochrane Library we
      identified clinical studies on the treatment of combined SLAP and rotator cuff
      lesions. Study quality was assessed using levels of evidence and a modified Jadad
      score. Clinical outcome was assessed through scores and range of motion
      assessments. RESULTS: We included 7 studies of 374 patients with a mean age of 53
      +/- 11 years followed for 35 +/- 13 months. Combined lesions have a significant
      negative effect on isolated rotator cuff or SLAP repair. Patients older than 45
      years of age had a significantly better clinical result after biceps tenotomy
      than SLAP repair with concomitant rotator cuff repair. Biceps tenotomy plus
      rotator cuff repair showed significantly better range of motion for flexion and
      rotation than SLAP plus rotator cuff repair. CONCLUSION: The frequent combination
      of SLAP and rotator cuff injury should be considered during assessment and
      informed consent of shoulder patients. While young patients and isolated SLAP
      lesions show excellent clinical results after elective repair, combined lesions
      should be treated with biceps tenotomy and/or debridement plus rotator cuff
      repair in patients older than 45 years.

PMID- 24129724
TI  - [Are 55 cents always better value than 90 cents for venous thromboembolism
      prophylaxis? Comparison of three low-molecular-weight heparins with regard to
      economics and guideline compliance].
AB  - BACKGROUND: Four low-molecular-weight heparins with different dosage regimens are
      allowed for venous thromboembolism prophylaxis in patients with a high risk of
      thromboembolism in Germany. If comparison is made purely on the basis of drug
      costs, multi-dose vials are the favourable solution. We try to answer the
      question whether the choice of low-molecular-weight heparin influences the
      compliance with the S2 guideline "Inpatient and outpatient thromboembolism
      prophylaxis in surgery and perioperative medicine." Beyond that we ask if multi
      dose administration is superior to the pre-filled syringe when total costs are
      calculated on the basis of procedure and technical application. PATIENTS AND
      METHODS: After training the nursing and medical staff in guideline-compliant
      implementation of thromboembolism prophylaxis with pre-filled certoparin safety
      syringes (03/09-05/09) or nadroparin (06/09-08/09) and enoxaparin (02/10-04/10)
      from multi-dose vials, we calculated the total costs on the basis of procedure
      and technical application. Furthermore, the satisfaction of the nursing staff was
      interrogated and the proportion of non-guideline-compliant prescriptions was
      determinated prospectively on the basis of a total of 388 patient files. RESULTS:
      When total costs are calculated on the basis of procedure and technical
      application, the costs for nadroparin are 1.16 ?/0.3 mL, 1.30 ?/0.4 mL and 1.58
      ?/0.6 mL, for enoxaparin 1.04 ?/20 and 1.42 ?/40, and for certoparin 1.25 ?/pre
      filled safety syringe. The pre-filled certoparin safety syringe made a very good
      overall impression on the nursing staff (versus sufficient for nadroparin and
      enoxaparin). Guideline-compliance was achieved in 100 % with body weight- and
      risk-independent certoparin, in 79.4 % with risk-adapted enoxaparin, and in 66.4
      % with body weight- and risk-dependent nadroparin. CONCLUSION: The complexity of
      the dosage regimen of a low-molecular-weight heparin has a decisive influence on
      guideline-compliance. By calculating total costs on the basis of procedure and
      technical application multi-dose vials only offer a price advantage in patients
      with a low or moderate risk of thromboembolism compared with pre-filled safety
      syringes in the venous thromboembolism prophylaxis of orthopaedic and trauma
      surgery patients.

PMID- 24129725
TI  - [Elastic titanium nails for minimally invasive intramedullary splinting of
      metacarpal fractures].
AB  - AIM: The goal in treatment of metacarpal fractures is to restore the normal
      function of the hand. Although a majority of these fractures can be treated non
      operatively, surgery is recommended for displaced fractures and in case of a
      patient wish for primary stability for practise. A poor clinical outcome is
      described for metacarpal shortening of more than 5 millimeters and for rotational
      deformity. Whereas plate osteosynthesis may lead to soft tissue irritation
      involving tendon adhesions and scar formation, we have used the elastic stable
      intramedullary nailing [ESIN] technique using titanium elastic nails (TEN) for
      intramedullary splinting of short metacarpal shaft and neck fractures. METHOD:
      Within 5 years, ESIN was performed in 95 patients. The operative technique was
      evaluated retrospectively concerning its functional results and complications.
      RESULTS: Sixty-three patients were analysed after an average follow-up of 14.0 +/
      5.2 weeks. The mean DASH-Score was 2.3 +/- 3.9 points. We saw one implant out-of
      position and three cases of skin irritation affording TEN shortening. Two
      superficial wound infections were treated conservatively. Pseudarthrosis and nail
      breakage were not observed. After TEN removal 9 +/- 2.4 weeks post implantationem
      no refracture occurred. CONCLUSION: Minimally invasive intramedullary
      stabilisation of short metacarpal shaft and neck fractures with a TEN is a safe
      surgical technique and achieves primary stability for practise. It reliably leads
      to fracture healing and produces excellent functional results.

PMID- 24129726
TI  - [Arthroplasty for fractures of the femur near the hip joint].
AB  - The incidence of proximal fractures of the femur will increase with the
      demographic change in the German population. Besides osteosynthesis, which in
      most cases of femoral neck, pertrochanteric and femoral head fracture is the
      method of choice, arthroplasty of the hip is likewise an established therapy.
      Indications are dislocated femoral neck fractures of the elderly. But there are
      good results for arthroplasty after proximal femoral fractures in younger active
      patients as well, when the fracture was not recognized or treated immediately.
      The outcome of hip arthroplasty after fracture is influenced by the elderly and
      unhealthy patient himself and the difficult planning and operation conditions due
      to fracture and its morphology. Most important for the best result are an
      interdisciplinary preparation of the patient and a well-planned surgery. In these
      cases common complications like thromboembolism, massive intraoperative blood
      loss and general infections like urinary tract infection can be reduced. For hip
      arthroplasty after fracture total hip replacement as well as hemiarthroplasty
      with bipolar prosthesis should be considered. The implant chosen and the
      implantation technique with or without bone cement has to be determined. Facts
      like the general state of health, biological age, level of activity and
      comorbidities should be taken into account appropriately. 

PMID- 24129727
TI  - [Physiological properties and functions of microglia].
AB  - Microglia, the resident immune effective cells of the central nervous system,
      play crucial roles in mediating immune-related process. It becomes activated
      quickly in response to even minor pathological insults and participates in series
      of immune responses. Under physiological conditions, most microglia stay in a
      typical resting state, with ramified processes continuously extending and
      retracting from surrounding neural tissues, suggesting an important function of
      resting microglia. Recent studies indicate that resting microglia can regulate
      many physiological processes, including neural development, neural circuit
      formation, neuronal activity and plasticity, and animal grooming behavior. Here,
      we review the properties of resting microglia and further discuss how microglia
      participate in the above-mentioned functional regulation under physiological
      conditions. 

PMID- 24129728
TI  - [Progress of study on neuritin].
AB  - Neuritin is a new member of the neurotrophic factor family, whose gene is named
      cpg15 (candidate plasticity-related gene 15) and can be activated by neural
      activity or neurotrophins (NTs). Experiments show that neuritin is able to
      promote the growth and branching of neurites, and plays an important role in
      neuronal plasticity and neuronal regeneration. Recent studies have proved that
      neuritin is not only involved in the regulation of various physiological
      functions in the nervous system, but also related in angiogenesis and
      tumorigenesis. Here we review the mechanisms involved in cpg15 expression and
      regulation, biological effects of neuritin, and how neuritin plays its biological
      activities. The hot issues and difficulties in the study of neuritin are also
      discussed. 

PMID- 24129729
TI  - [Involvement of peripheral NFkappaB in tetanic sciatic stimulation-induced
      neuropathic pain].
AB  - Tetanic stimulation of the sciatic nerve (TSS) induces long-term potentiation
      (LTP) of both C- and A-fiber-evoked field potentials in the spinal dorsal horn
      and long-lasting mechanical allodynia in rats. Though central mechanisms
      underlying those phenomena have been well studied, peripheral mechanisms still
      remain poorly known. Nuclear factor kappa B (NFkappaB) is an important
      transcription factor. In the spinal cord, NFkappaB plays a key role in regulating
      the expression of numerous pro-inflammation factors and contributes to glial
      activation in central nervous system, suggesting the involvement of spinal
      NFkappaB in central sensitization. To address whether NFkappaB in the dorsal root
      ganglion (DRG) participates in peripheral sensitization, we examined NFkappaB
      expression in the DRG and the effect of inhibiting NFkappaB activation on
      neuropathic pain using behavior test, Western blot analysis and
      immunohistochemical approaches. The results showed that TSS induced long-lasting
      mechanical allodynia in bilateral hind paws and increased phospho-NFkappaB
      expression in the bilateral DRG. The activated NFkappaB mainly expressed in
      nuclei not only of neurons, but also of Schwann cells and satellite glial cells.
      Moreover, NFkappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly
      alleviated TSS-induced allodynia. Our results suggest that peripheral NFkappaB
      may be involved in TSS-induced neuropathic pain, and provide new evidence for the
      peripheral mechanism of 'mirror pain'. 

PMID- 24129730
TI  - [Effects of hypoxia conditioned medium of cerebral cortex cells on the
      differentiation of neural stem cells and related signal pathways].
AB  - The aim of this study was to investigate the effects of hypoxia conditioned
      medium (HCM) of cerebral cortex cells on the differentiation of neural stem cells
      (NSCs) and to clarify the signal transduction mechanism. The cerebral cortex
      cells from newborn SD rats were primarily cultured for 5 d, and then the cells
      were cultured in environments of 4% O2, 1% O2 and normal oxygen concentration,
      respectively, for 6 h. The culture mediums were collected and centrifuged as the
      HCM and normoxia conditioned medium (NCM). The neurospheres of NSCs were obtained
      from the rat cerebral cortex by suspending culture. Immunohistochemical staining
      was used after adherence culture for 48 h to identify neurons and astrocytes in
      the progeny of NSCs. LY294002, a PI3-K inhibitor, and SP600125, a JNK inhibitor,
      were added into the HCM to culture NSCs for 48 h. The results showed that NSCs in
      the cerebral cortex could differentiate into beta-Tubulin III immunoreactive
      neurons and GFAP immunoreactive astrocytes in three conditioned mediums, and the
      neurons proportion in progeny of NSCs was higher than astrocytes in all three
      groups. The proportion of neurons in 4% HCM was higher than that in NCM (P <
      0.01). But the proportion of neurons in 1% HCM was less than that in NCM (P <
      0.01). Both LY294002 and SP600125 inhibited NSCs to differentiate into high
      proportion neurons induced by 4% HCM (P < 0.01), but the inhibitory effect of
      LY294002 was stronger than that of SP600125 (P < 0.01). In conclusion, 4% HCM can
      induce NSCs to differentiate into more neurons mainly through the PI3-K pathway. 

PMID- 24129731
TI  - [Influence of prenatal alcohol exposure on retinal development and cell
      differentiation].
AB  - The aim of the present study was to investigate the effects of prenatal alcohol
      exposure (PAE) on the development and cell differentiation of retina in
      offspring. The mouse model of PAE was made. HE staining and immunofluorescent
      labeling were carried out to visualize the structure, development and cell
      differentiation of the retina from postnatal day 0 (P0)-P30 offspring. The
      results showed that PAE can lead to the retardation of retinal development, the
      reduction of number of bipolar cells and horizontal cells, the disorder of
      horizontal cells' polarity, as well as the retinal thickening in a dose-dependent
      manner. The data suggest that alcohol exposure during pregnancy can lead to the
      developmental retardation of retina and decreased number of bipolar cells and
      horizontal cells in the retina of offspring. 

PMID- 24129732
TI  - [Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic
      membrane and invasion of breast cancer cells via downregulation of AEG-1 and MMP
      2].
AB  - The purpose of the present study was to investigate the effect of luteolin on the
      angiogenesis and invasion of breast cancer cells. MTT assay was used to examine
      breast cancer proliferation. The chick chorioallantoic membrane model was used to
      assess the angiogenesis effect. Wound healing assay was used to assess cell
      invasion ability. Western blot was used to analyze Bcl-2, AEG-1 and MMP-2
      expression levels. The results showed luteolin inhibited MCF-7 cells
      proliferation in a dose- and time-dependent manner, and the expression of Bcl-2
      protein was decreased. Luteolin had a strong anti-angiogenesis of chick
      chorioallantoic membrane. After treatment of MCF-7 cells with luteolin at 60
      MUmol/L for 48 h, migration rate was reduced by 71.07% compared with control (P <
      0.01). After treatment of MCF-7 cells with luteolin at 60 MUmol/L for 48 h, the
      expression of AEG-1 and MMP-2 was reduced by 82.34% (P < 0.05) and 85.70% (P <
      0.05) respectively, compared with control. In conclusion, the results suggest
      that luteolin can inhibit the proliferation of breast cancer cells, and suppress
      the expression of Bcl-2. Furthermore, luteolin has strong anti-angiogenesis of
      chick chorioallantoic membrane and anti-invasive activity on breast cancer cells,
      and down-regulates the expression of AEG-1 and MMP-2. 

PMID- 24129733
TI  - [Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on
      proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].
AB  - The present study was to investigate the effects of exogenous insulin-like growth
      factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer
      cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro,
      the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells
      (IC50 of IGFBP7 = 8.49 MUg/mL) in time- and concentration-dependent manner.
      SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous
      IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced
      G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7
      promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1),
      and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced
      regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the
      present study suggests that exogenous IGFBP7 could activate the p38(MAPK)
      signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation
      of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells. 

PMID- 24129734
TI  - [Interrelation between the hypothalamic arcuate nucleus and the bone variation of
      osteoporosis in rats].
AB  - This study investigated the interrelation between the hypothalamic arcuate
      nucleus (ARC) and the bone variation of osteoporosis in rats. Four animal models
      of ovariectomy-induced osteoporosis (OVX), glucocorticoid-induced osteoporosis
      (GIOP), retinoic acid-induced osteoporosis (RAOP) and senile osteoporosis (SOP)
      were used to study the influence of osteoporosis on ARC. Ovariectomized rats were
      further treated with thymopeptide, ciclosporin and exercise respectively to
      detect the changes of ARC nerve cells number. The results showed that: (1) The
      OVX, GIOP, RAOP and SOP models were successfully established, showing
      osteoporosis as well as decrease of the number of ARC nerve cells; (2)
      Thymopeptide and exercise respectively alleviated the bone loss induced by
      ovariectomy, accompanied by increase of the number of ARC nerve cells, while
      ciclosporin further increased the bone loss of ovariectomized rats, accompanied
      by further decrease of the number of ARC nerve cells. These results suggest that
      there is a close interrelationship between ARC and osteoporosis in rat. There is
      a hypothalamus-pituitary-bone (HPB) axis, and HPB axis regulates the mechanism of
      osteoporosis in rats. 

PMID- 24129735
TI  - [Effect of spontaneous firing of injured dorsal root ganglion neuron on
      excitability of wide dynamic range neuron in rat spinal dorsal horn].
AB  - The aim of the paper is to study the effect of spontaneous firing of injured
      dorsal root ganglion (DRG) neuron in chronic compression of DRG (CCD) model on
      excitability of wide dynamic range (WDR) neuron in rat spinal dorsal horn. In
      vivo intracellular recording was done in DRG neurons and in vivo extracellular
      recording was done in spinal WDR neurons. After CCD, incidence of spontaneous
      discharge and firing frequency enhanced to 59.46% and (4.30 +/- 0.69) Hz
      respectively from 22.81% and (0.60 +/- 0.08) Hz in normal control group (P <
      0.05). Local administration of 50 nmol/L tetrodotoxin (TTX) on DRG neuron in CCD
      rats decreased the spontaneous activities of WDR neurons from (191.97 +/-
      45.20)/min to (92.50 +/- 30.32)/min (P < 0.05). On the other side, local
      administration of 100 mmol/L KCl on DRG neuron evoked spontaneous firing in a
      reversible way (n = 5) in silent WDR neurons of normal rats. There was 36.36%
      (12/33) WDR neuron showing after-discharge in response to innocuous mechanical
      stimuli on cutaneous receptive field in CCD rats, while after-discharge was not
      seen in control rats. Local administration of TTX on DRG with a concentration of
      50 nmol/L attenuated innocuous electric stimuli-evoked after-discharge of WDR
      neurons in CCD rats in a reversible manner, and the frequency was decreased from
      (263 +/- 56.5) Hz to (117 +/- 30) Hz (P < 0.05). The study suggests that the
      excitability of WDR neurons is influenced by spontaneous firings of DRG neurons
      after CCD. 

PMID- 24129736
TI  - [Effect of different altitudes on telomere length of rat peripheral blood
      leukocyte].
AB  - The present study was aimed to investigate the effect of different altitudes on
      telomere length of rat peripheral blood leukocyte and possible mechanism. Sixty
      male rats were randomly divided into three groups, lower altitude control group
      (10 m), moderate altitude group (2 260 m) and very high altitude group (simulated
      5 000 m). The moderate altitude group and very high altitude group rats were
      transported to Xining and hypobaric chamber in Qinghai University, respectively.
      The peripheral blood specimens were extracted 30 d after the transportation. By
      means of real-time PCR, automatic blood cell analyzer, ELISA, TBA and WST-1
      methods, the telomere lengths of blood leukocyte, the hemoglobin (Hb) contents,
      the plasma levels of telomerase reverse transcriptase (TERT) and hypoxia
      inducible factor 1alpha (HIF-1alpha), the plasma content of malondialdehyde (MDA)
      and superoxide dismutase (SOD) activity were measured, respectively. The results
      showed that the telomere lengths of peripheral blood leukocyte in moderate
      altitude group were longer than those in control group and very high altitude
      group. The changes of TERT were compatible with the telomere length of peripheral
      blood leukocyte under different altitudes. The levels of HIF-1alpha in moderate
      altitude group and very high altitude group were higher than that of control
      group. The very high altitude group showed decreased SOD activities and increased
      level of MDA, compared with the other two groups. These results suggest that the
      telomere lengths of rat peripheral blood leukocyte in moderate altitude are
      elongated, and that the telomere-elongating effect is lost under very high
      altitude. The changes of HIF-1alpha, TERT and oxidative stress damage are the
      main mechanisms of telomere length changes. Moderate altitude living might be
      beneficial to increasing the life span in mammals. 

PMID- 24129737
TI  - [Impaired effect of BHC80 gene knock-down on the cardiac development in
      zebrafish].
AB  - The effect of BHC80 (a component of BRAF-HDAC complex) on development was not
      well studied, because BHC80 gene knock-out mice died in one day after birth.
      Interestingly, zebrafish embryos can live, even if their important organs like
      cardiac system has severe dysfunction, as 25%-40% O2 are supplied through their
      skin. Therefore, a model of BHC80 gene knock-down zebrafish embryos was
      established to explore the effect of BHC80 on the early embryonic development.
      BHC80-morpholino antisense oligonucleotides 2 (BHC80-MO2) was designed and
      injected into zebrafish embryos to interrupt the correct translation of BHC80
      mRNA at one or two cells stage, which was proved by RT-PCR analysis. Two control
      groups, including non-injection group and control-MO (con-MO) injection group,
      and four different doses of BHC80-MO2 injection groups, including 4 ng, 6 ng, 8
      ng and 10 ng per embryo were set up. The embryonic heart phenotype and cardiac
      function were monitored, analyzed and compared between con-MO and BHC80-MO2
      groups by fluorescence microscope in vmhc:gfp transgenic zebrafish which express
      green fluorescent protein in ventricle. The results showed that BHC80-MO2
      microinjection effectively knocked down the BHC80 gene expression, because the
      BHC80-MO2 group emerged a new 249 bp band which reduced 51 bp compared to 300 bp
      band of con-MO group in RT-PCR analysis, and the 51 bp was the extron 10. The
      abnormal embryo rate rose with the increase of BHC80-MO2 dosage. The proper BHC80
      MO2 injection dosage was 8 ng per embryo, as minor embryos had abnormal phenotype
      in 4 ng and 6 ng per embryo groups and most embryos died in 10 ng per embryo
      group. BHC80-MO2 embryos exhibited abnormal cardiac phenotype, including
      imbalance of the proportion of heart ventricle to atrium, incomplete D-loop, even
      tubular heart, slow heart rates and cardiac dysfunction. The results from a model
      of BHC80 gene knock-down zebrafish embryos show that the abnormal cardiac
      phenotype and cardiac dysfunction of BHC80-MO2 embryos may be one of the probable
      reasons for the BHC80 gene knock-out mice death, which would provide a good
      research model to clarify the mechanism of cardiac development. 

PMID- 24129738
TI  - [Involvement of store-operated calcium channels and receptor-operated calcium
      channels in Ca(2+)-sensing receptor-evoked extracellular Ca(2+) influx and NO
      generation in human umbilical vein endothelial cells].
AB  - This paper aims to investigate the effect of store-operated calcium channels
      (SOC) and receptor-operated calcium channels (ROC) on Ca(2+)-sensing receptor
      (CaR)-induced extracellular Ca(2+) influx and nitric oxide (NO) generation in
      human umbilical vein endothelial cells (HUVEC). SOC blocker, non-selective cation
      channel blocker, ROC agonist and ROC blocker were used separately and combined.
      Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured by Fura-2/AM loading.
      The activity of endothelial nitric oxide synthase (eNOS) and the production of NO
      were determined by the DAF-FM diacetate (DAF-FM DA). The results showed that
      increases of [Ca(2+)]i, eNOS activity and NO generation induced by CaR agonist
      Spermine were all reduced after single blocking the SOC or ROC, respectively (P <
      0.05). ROC agonist can partially abolish the ROC blocker's effect (P < 0.05). The
      above mentioned effects evoked by CaR agonist Spermine were further reduced when
      blocking both SOC and ROC than single blocking SOC or ROC in HUVEC (P < 0.05). In
      conclusion, these results suggest that the SOC and ROC participate in the
      processes of CaR-evoked extracellular Ca(2+) influx and NO generation by a
      synergistic manner in HUVEC. 

PMID- 24129740
TI  - Immune balance: the development of the idea and its applications.
AB  - It has long been taken for granted that the immune system's capacity to protect
      an individual from infection and disease depends on the power of the system to
      distinguish between self and nonself. However, accumulating data have undermined
      this fundamental concept. Evidence against the self/nonself discrimination model
      left researchers in need of a new overarching framework able to capture the
      immune system's reactivity. Here, I highlight that along with the self/nonself
      model, another powerful representation of the immune system's reactivity has been
      developed in the twentieth century immunology. According to this alternative
      view, the immune system is not a killer of nonself strangers but a peace-maker
      helping to establish harmony with the environment. The balance view of the system
      has never become part of the dominant paradigm. However, it is gaining more and
      more currency as new research develops. Advances in mucosal immunology confirm
      that instead of distinguishing between self and foreign the immune system reacts
      to microbial, chemical and self-induced alterations to produce responses that
      counterbalance effects of these changes. 

PMID- 24129739
TI  - Composite fluorescent nanoparticles for biomedical imaging.
AB  - PURPOSE: In the rapidly expanding field of biomedical imaging, there is a need
      for nontoxic, photostable, and nonquenching fluorophores for fluorescent imaging.
      We have successfully encapsulated a new, extremely hydrophobic, pentacene-based
      fluorescent dye within polymeric nanoparticles (NPs) or nanocarriers (NCs) via
      the Flash NanoPrecipitation (FNP) process. PROCEDURES: Nanoparticles and dye
      loaded micelles were formulated by FNP and characterized by dynamic light
      scattering, fluorescence spectroscopy, UV-VIS absorbance spectroscopy, and
      confocal microscopy. RESULTS: These fluorescent particles were loaded from less
      than 1% to 78% by weight core loading and the fluorescence maximum was found to
      be at 2.3 wt.%. The particles were also stably formed at 2.3% core loading from
      20 up to 250 nm in diameter with per-particle fluorescence scaling linearly with
      the NC core volume. The major absorption peaks are at 458, 575, and 625 nm, and
      the major emission peaks at 635 and 695 nm. In solution, the Et-TP5 dye displays
      a strong concentration-dependent ratio of the emission intensities of the first
      two emission peaks, whereas in the nanoparticle core the spectrum is independent
      of concentration over the entire concentration range. A model of the fluorescence
      quenching was consistent with Forster resonant energy transfer as the cause of
      the quenching observed for Et-TP5. The Forster radius calculated from the
      absorption and emission spectra of Et-TP5 is 4.1 nm, whereas the average dye
      spacing in the particles at the maximum fluorescence is 3.9 nm. CONCLUSIONS: We
      have successfully encapsulated Et-TP5, a pentacene derivative dye previously only
      used in light-emitting diode applications, within NCs via the FNP process. The
      extreme hydrophobicity of the dye keeps it encapsulated in the NC core, its
      extended pentacene structure gives it relatively long wavelength emission at 695
      nm, and the pentacene structure, without oxygen or nitrogen atoms in its core,
      makes it highly resistant to photobleaching. Its bulky side groups minimize self
      quenching and localization within the nanoparticle core prevents interaction of
      the dye with biological surfaces, or molecules in diagnostic assays. Loading of
      dye in the NP core allows 25 times more dye to be delivered than if it were
      conjugated onto the nanocarrier surface. The utility of the dye for quantifying
      nanoparticle binding is demonstrated. Studies to extend the wavelength range of
      these pentacene dyes into the near infra-red are underway.

PMID- 24129741
TI  - A facile strategy to decorate Cu9S5 nanocrystals on polyaniline nanowires and
      their synergetic catalytic properties.
AB  - Here, we demonstrated a novel method to decorate Cu9S5 nanocrystals on
      polyaniline (PANI) nanowires using the dopant of mercaptoacetic acid (MAA) in the
      PANI matrix as the sulfur source under a hydrothermal reaction. TEM images showed
      that Cu9S5 nanocrystals with a size in the range of 5-20 nm were uniformly formed
      on the surface of PANI nanowires. Significantly, the as-prepared PANI/Cu9S5
      composite nanowires have been proven to be novel peroxidase mimics toward the
      oxidation of the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the
      presence of H2O2. Due to the synergetic effects between polyaniline nanowires and
      Cu9S5 nanocrystals, the obtained PANI/Cu9S5 composite nanowires exhibit superior
      catalytic activity over the independent components. This work not only presents a
      simple and versatile method to decorate semiconductor nanocrystals on the surface
      of conducting polymer nanostructures, but also provides fundamental guidelines
      for further investigations into the synergetic effect between conducting polymers
      and other materials.

PMID- 24129742
TI  - Cost-effective isobaric tagging for quantitative phosphoproteomics using DiART
      reagents.
AB  - We describe the use of an isobaric tagging reagent, Deuterium isobaric Amine
      Reactive Tag (DiART), for quantitative phosphoproteomic experiments. Using DiART
      tagged custom mixtures of two phosphorylated peptides from alpha casein and their
      non-phosphorylated counterparts, we demonstrate the compatibility of DiART with
      TiO2 affinity purification of phosphorylated peptides. Comparison of theoretical
      vs. experimental reporter ion ratios reveals accurate quantification of
      phosphorylated peptides over a dynamic range of more than 15-fold. Using DiART
      labelling and TiO2 enrichment (DiART-TiO2) with large quantities of proteins (8
      mg) from the cell lysate of model fungus Aspergillus nidulans, we quantified 744
      unique phosphopeptides. Overlap of median values of TiO2 enriched phosphopeptides
      with theoretical values indicates accurate trends. Altogether these findings
      confirm the feasibility of performing quantitative phosphoproteomic experiments
      in a cost-effective manner using isobaric tagging reagents, DiART. 

PMID- 24129743
TI  - Perioperative considerations for neurosurgical procedures in the gravid patient:
      Continuing Professional Development.
AB  - PURPOSE: The complexity of neurosurgical procedures and their interactions with
      maternal and fetal physiologies are key factors in determining the overall
      maternal and fetal outcome. The literature and guidelines provide only partial
      information regarding the standard of care in these cases. The purpose of this
      Continuing Professional Development module is to review the issues related to
      common neurosurgical conditions and their optimal anesthetic management.
      PRINCIPAL FINDINGS: The most common neurosurgical conditions found in pregnancy
      include brain tumours, cerebrovascular diseases, spinal pathologies, and
      neurotrauma. Though rare, these conditions and related procedures may affect
      maternal and fetal outcome. Maternal considerations should be given priority in
      cases of emergent surgeries irrespective of trimester. In the early first
      trimester, risk of fetal loss and congenital malformation are substantial; hence,
      proper counselling should be given to the mother with special emphasis on
      therapeutic abortion. When indicated, anticonvulsants should be started as early
      as possible and continued throughout pregnancy. Surgical procedures can be
      performed with relative safety during the second trimester and early third
      trimester. After 34 weeks, delivery seems to be the first choice, and the role of
      regional anesthesia in this situation should be carefully planned after proper
      review of neurosurgical pathology and maternal condition. During acute
      neurological deterioration, however, Cesarean delivery under general anesthesia
      should be anticipated. CONCLUSION: A multidisciplinary approach with good
      communication amongst all team members certainly plays a crucial role for
      successful management of such cases.

PMID- 24129744
TI  - Glatiramer acetate: a review of its use in patients with relapsing-remitting
      multiple sclerosis and in delaying the onset of clinically definite multiple
      sclerosis.
AB  - Glatiramer acetate (Copaxone((r))) is a synthetic analogue of the multiple
      sclerosis (MS)-associated antigen, myelin basic protein. Although its exact
      mechanisms of action in MS remain to be fully elucidated, the key mechanisms of
      action of glatiramer acetate appear to be modulation of the inflammatory response
      and neuroprotective and/or neuroregenerative effects. Subcutaneous glatiramer
      acetate is indicated for the treatment of adult patients with relapsing-remitting
      MS (RRMS) and the treatment of patients who have experienced a well-defined first
      clinical episode and have magnetic resonance imaging (MRI) features consistent
      with MS or have been determined to be at high risk of developing clinically
      definite MS (CDMS). In clinical trials in patients with RRMS, glatiramer acetate
      reduced the frequency of relapses and reduced the burden and activity of disease
      on MRI, was more effective than placebo and showed generally similar efficacy to
      subcutaneous interferon (IFN) beta-1a and IFNbeta-1b. Furthermore, the beneficial
      effects of glatiramer acetate were sustained during up to 15 years of treatment
      in an extension study. In patients with clinically isolated syndrome (CIS),
      glatiramer acetate significantly delayed the onset of CDMS compared with placebo.
      The drug was generally well tolerated in these patient populations, with
      injection-site reactions being the most commonly occurring adverse events.
      Therefore, glatiramer acetate remains a valuable first-line option in the
      treatment of RRMS and is an option for delaying the onset of CDMS in patients
      with CIS.

PMID- 24129745
TI  - Oral-aboral identity displayed in the expression of HpHox3 and HpHox11/13 in the
      adult rudiment of the sea urchin Holopneustes purpurescens.
AB  - Hox genes are noted for their roles in specifying axial identity in bilateral
      forms. In the radial echinoderms, the axis whose identity Hox genes might specify
      remains unclear. From the expression of Hox genes in the development of the sea
      urchin Holopneustes purpurescens reported here and that reported previously, we
      clarify the axis that might be specified by Hox genes in echinoderms. The
      expression of HpHox11/13 here is described at three developmental stages. The
      expression is around the rim of the blastopore in gastrulae, in the archenteron
      wall and adjacent mesoderm in early vestibula larvae, and in a patch of mesoderm
      close to the archenteron wall in later vestibula larvae. The retained expression
      of HpHox11/13 in the patch of mesoderm in the later vestibula larvae is, we
      suggest, indicative of a posterior or an aboral growth zone. The expression of
      HpHox3 at the echinoid-rudiment stage, in contrast, is in oral mesoderm beneath
      the epineural folds, concentrated in sites where the first three adult spines
      form. With the expression of HpHox5 and HpHox11/13 reported previously, the
      expressions here support the role of Hox genes in specifying oral-aboral identity
      in echinoderms. How such specification and a posterior growth zone add support to
      a concept of the structural homology between echinoderms and chordates is
      discussed. 

PMID- 24129746
TI  - P-Cl bond-induced lactamization of 2(2'-hydroxyl)phenyloxazoline to form a cyclic
      phosphinite, 3-(2-chloroethyl)-2-phenyl-2H-benzo[e][1,3,2]oxaza-phosphinin-4(3H)
      one: synthesis, structural studies and transition metal complexes.
AB  - The equimolar reaction between 2(2'-hydroxy)phenyloxazoline (1) and PPhCl2 in the
      presence of triethylamine afforded an unexpected cyclic product, phenyl-benzo
      oxazaphosphininone (2), instead of a simple phosphinite derivative A. A similar
      reaction between 1 and PPhCl2 in 2 : 1 ratio also yielded the same product 2, but
      with one equivalent of 2(2'-hydroxy)phenyloxazoline (1) left unreacted. The
      formation of the cyclic product 2 is due to the P-Cl bond induced oxazoline ring
      opening followed by the formation of a six-membered gamma-lactam type product, 3
      (2-chloroethyl)-2-phenyl-2H-benzo[e][1,3,2]oxazaphosphinin-4(3H)-one (2 also
      referred to as L). The reactions of 2 with H2O2, elemental sulphur or elemental
      selenium yielded the corresponding chalcogenides, LE (3, E = O; 4, E = S; 5, E =
      Se) in quantitative yield. Treatment of 2 with [Ru(eta(6)-Cymene)Cl2]2,
      [Pd(COD)Cl2] and [Pd(eta(3)-C3H5)Cl]2 resulted in the formation of [RuCl2(eta(6)
      cymene)(L)] (6), [PdCl2{L}2] (7), and [Pd(eta(3)-C3H5)Cl(L)] (8), respectively.
      The compound 2 obtained in the 2 : 1 reaction when treated with [Pd(eta(3)
      C3H5)Cl]2 gave the same palladium complex 8 (referred to as 9a), but co
      crystallized with bis(oxazolyl)palladacycle (9b) as confirmed by single crystal X
      ray analysis. 

PMID- 24129747
TI  - Bauhinia championi (Benth.) Benth. polysaccharides upregulate Wnt/beta-catenin
      signaling in chondrocytes.
AB  - Bauhinia championi (Benth.) Benth. polysaccharides (BCBPs), extracted from
      Bauhinia championi (Benth.) Benth., which has been used in traditional Chinese
      medicine (TCM) for the treatment of osteoarthritis (OA), are the bioactive
      constituents of Bauhinia championi (Benth.) rattan. However, the molecular
      mechanisms responsible for their effects on OA are poorly understood. The
      Wnt/beta-catenin signaling pathway plays an important role in the proliferation
      of chondrocytes. In the present study, the effects of BCBPs on Wnt/beta-catenin
      signaling in chondrocytes were investigated. BCBPs were obtained by hot-water
      extraction and identified by the modified high performance liquid chromatography
      (HPLC) method. Chondrocytes were isolated from the knees of Sprague-Dawley rats
      and identified by type II collagen immunohistochemistry. The chondrocytes were
      treated with or without BCBPs for 48 h. Cell viability was evaluated by MTT
      assay. The mRNA and protein levels of Wnt-4, beta-catenin, Frizzled-2, glycogen
      synthase kinase (GSK)-3beta, cyclin D1 and collagen II were detected by western
      blot analysis and reverse transcription PCR (RT-PCR), respectively. We found that
      the BCBPs contained at least seven monosaccharides, including D-mannose,
      rhamnose, D-(+) glucuronic acid, D-(+) galacturonic acid, D-glucose, galactose
      and arabinose. The cell viability of the chondrocytes treated with 50, 100 and
      200 ug/ml BCBPs was significantly higher than that of the chondroctyes in the
      control group (treated with 0 ug/ml BCBPs). Furthermore, compared with the
      control group, the mRNA and protein expression of Wnt-4, beta-catenin, Frizzled-2
      and cyclin D1 in the BCBP-treated groups markedly increased, whereas the mRNA and
      protein expression of GSK-3beta significantly decreased. Of note, the dose of 100
      ug/ml BCBPs was more effective than the dose of 50 ug/ml BCBPs and 200 ug/ml
      BCBPs. In addition, we found that treatment with BCBPs upregulated the protein
      levels of collagen II in the chondrocytes. These results indicate that BCBPs
      upregulate Wnt/beta-catenin signaling, thus promoting chondrocyte proliferation. 

PMID- 24129748
TI  - Single-cell resolution mapping of neuronal damage in acute focal cerebral
      ischemia using thallium autometallography.
AB  - Neuronal damage shortly after onset or after brief episodes of cerebral ischemia
      has remained difficult to assess with clinical and preclinical imaging techniques
      as well as with microscopical methods. We here show, in rodent models of middle
      cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral
      ischemia can be mapped with single-cell resolution using thallium
      autometallography (TlAMG), a histochemical technique for the detection of the
      K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice
      with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that
      releases Tl(+) after crossing the blood-brain barrier. We found, within the
      territories of the affected arteries, areas of markedly reduced neuronal Tl(+)
      uptake in all animals at all time points studied ranging from 15 minutes to 24
      hours after MCAO. In large lesions at early time points, areas with neuronal and
      astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative
      penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the
      areas of reduced Tl(+)uptake matched with areas delineated by established markers
      of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and
      clinical single-photon emission computed tomography (SPECT) imaging of hyperacute
      alterations in brain K(+) metabolism and prediction of tissue viability in
      cerebral ischemia. 

PMID- 24129749
TI  - Impaired cerebrovascular hemodynamics are associated with cerebral white matter
      damage.
AB  - White matter hyperintensities (WMH) in elderly individuals with vascular diseases
      are presumed to be due to ischemic small vessel diseases; however, their etiology
      is unknown. We examined the cross-sectional relationship between cerebrovascular
      hemodynamics and white matter structural integrity in elderly individuals with
      vascular risk factors. White matter hyperintensity volumes, fractional anisotropy
      (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75+/
      7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was
      assessed using transcranial Doppler ultrasound of the middle cerebral artery.
      Dynamic cerebral autoregulation was calculated from transfer function analysis
      (phase and gain) of spontaneous blood pressure and flow velocity oscillations in
      the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges.
      Higher PI was associated with greater WMH (P<0.005). Higher phase across all
      frequency ranges was associated with greater FA and lower MD (P<0.005). Lower
      gain was associated with higher FA in the LF range (P=0.001). These relationships
      between phase and FA were significant in the territories limited to the middle
      cerebral artery as well as across the entire brain. Our results show a strong
      relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss
      of cerebral white matter structural integrity (WMH and DTI metrics) in elderly
      individuals. 

PMID- 24129750
TI  - Effects of cerebral ischemic and reperfusion on T2*-weighted MRI responses to
      brief oxygen challenge.
AB  - This study characterized the effects of cerebral ischemia and reperfusion on T2*
      weighted magnetic resonance image (MRI) responses to brief oxygen challenge (OC)
      in transient (60 minutes) cerebral ischemia in rats. During occlusion, the
      ischemic core tissue showed no significant OC response, whereas the perfusion
      diffusion mismatch tissue showed markedly higher percent changes relative to
      normal tissue. After reperfusion, much of the pixels with initial exaggerated OC
      responses showed normal OC responses, and the majority of these tissues were
      salvaged as defined by endpoint T2 MRI. The initial core pixels showed
      exaggerated OC responses after reperfusion, but the majority of the core pixels
      eventually became infarct, suggesting exaggerated OC responses do not necessarily
      reflect salvageable tissue. Twenty-four hours after stroke, basal T1 increased in
      the ischemic core. Oxygen challenge decreased T1 significantly in the core,
      indicative of the substantial increases in dissolved oxygen in the core as the
      result of hyperperfusion. We concluded that exaggerated T2*-weighted MRI
      responses to OC offer useful insight in ischemic tissue fates. However,
      exaggerated OC pixels are not all salvageable, and they exhibited complex
      dynamics depending on reperfusion status, hyperperfusion, and edema effects. 

PMID- 24129752
TI  - Nitrogenase: a general hydrogenator of small molecules.
AB  - Nitrogenase naturally converts N2 to NH3, but it also hydrogenates a variety of
      small molecules, in many cases requiring multiple electrons plus protons for each
      catalytic cycle. A general mechanism, arising from many density functional
      calculations and simulations, is proposed to account for all of these reactions.
      Protons, supplied serially in conjunction with electrons to the active site FeMo
      co (a CFe7MoS9 (homocitrate) cluster), generate H atoms that migrate over and
      populate two S and two Fe atoms in the reaction domain. The mechanistic paradigm
      is conceptually straightforward: substrate (on Fe) and H atoms (on S and Fe) are
      bound contiguously in the reaction zone, and H atoms transfer (probably with some
      quantum tunneling) to the substrate to form product. Details and justifications
      of the mechanisms for N2 and other key substrates are summarised, and the unusual
      structure of FeMo-co as a general hydrogenation catalyst is rationalised. Testing
      experiments are suggested. 

PMID- 24129753
TI  - Measurement and stochastic modeling of kidney puncture forces.
AB  - The development of needle insertion robots and training simulators requires
      knowledge of the forces that arise when a needle is inserted into soft-tissue.
      The present study aims to construct stochastic models of the force required to
      puncture a kidney using a trocar needle, based on measurements. To this end, a
      total of sixty insertions were performed into porcine kidneys (ex vivo), at
      constant speed, using a linear motion stage. Axial force was measured at the
      needle hub and an ultrasound probe moved with the needle to enable identification
      of anatomical structures. Two force peaks were observed for each tissue layer
      punctured, one caused by the tip and one by the edge of the cannula. Based on
      ultrasound data these double-peaks were classified into four groups, related to
      kidney capsule and internal structures. Group size varied from 7 to 55 double
      peaks. Force peaks in each group were evaluated in terms of peak force and drop
      in force for both tip and cannula, and stochastic models were constructed that
      describe the multivariate distribution of these metrics. Peak forces in the
      capsule and internal structures ranged up to 2 N and 8 N, respectively. The
      resulting models can be used to simulate kidney puncture events in a variety of
      applications.

PMID- 24129754
TI  - Encapsulated neural stem cell neuronal differentiation in fluorinated
      methacrylamide chitosan hydrogels.
AB  - Neural stem/progenitor cells (NSPCs) are able to differentiate into the primary
      cell types (neurons, oligodendrocytes and astrocytes) of the adult nervous
      system. This attractive property of NSPCs offers a potential solution for neural
      regeneration. 3D implantable scaffolds should mimic the microstructure and
      dynamic properties found in vivo, enabling the natural exchange of oxygen,
      nutrients, and growth factors for cell survival and differentiation. We have
      previously reported a new class of materials consisting of perfluorocarbons
      (PFCs) conjugated to methacrylamide chitosan (MAC), which possess the ability to
      repeatedly take-up and release oxygen at beneficial levels for favorable cell
      metabolism and proliferation. In this study, the neuronal differentiation
      responses of NSPCs to fluorinated methacrylamide chitosan (MACF) hydrogels were
      studied for 8 days. Two treatments, with oxygen reloading or without oxygen
      reloading, were performed during culture. Oxygen concentration distributions
      within cell-seeded MACF hydrogels were found to have higher concentrations of
      oxygen at the edge of the hydrogels and less severe drops in O2 gradient as
      compared with MAC hydrogel controls. Total cell number was enhanced in MACF
      hydrogels as the number of conjugated fluorines via PFC substitution increased.
      Additionally, all MACF hydrogels supported significantly more cells than MAC
      controls (p < 0.001). At day 8, MACF hydrogels displayed significantly greater
      neuronal differentiation than MAC controls (p = 0.001), and among MACF groups
      methacrylamide chitosan with 15 fluorines per addition (MAC(Ali15)F) demonstrated
      the best ability to promote NSPC differentiation.

PMID- 24129755
TI  - Seeding cells on calcium phosphate scaffolds using hydrogel enhanced osteoblast
      proliferation and differentiation.
AB  - Internal pores in calcium phosphate (CaP) scaffolds pose an obstacle in cell
      seeding efficiency. Previous studies have shown inverse relationships between
      cell attachment and internal pore size, which mainly resulted from cells flowing
      to the bottom of culture plates. In order to overcome this structure-based
      setback, we have designed a method for cell seeding that involves hydrogel. CaP
      scaffolds fabricated with hydroxyapatite, biphasic calcium phosphate, and beta
      tricalcium phosphate, had respective porosities of 77.0, 77.9, and 82.5% and pore
      diameters of 671.1, 694.7, and 842.8 MUm. We seeded the cells on the scaffolds
      using two methods: the first using osteogenic medium and the second using
      hydrogel to entrap cells. As expected, cell seeding efficiency of the groups with
      hydrogel ranged from 92.5 to 96.3%, whereas efficiency of the control groups
      ranged only from 64.2 to 71.8%. Cell proliferation followed a similar trend,
      which may have further influenced early stages of cell differentiation. We
      suggest that our method of cell seeding with hydrogel can impact the field of
      tissue engineering even further with modifications of the materials or the
      addition of biological factors.

PMID- 24129757
TI  - Review of commonly used clinical pathology parameters for general
      gastrointestinal disease with emphasis on small animals.
AB  - A wide variety of markers are available to assess the function and pathology of
      the gastrointestinal (GI) tract. This review describes some of these markers with
      special emphasis given to markers used in dogs and cats. Small intestinal disease
      can be confirmed and localized by the measurement of serum concentrations of
      folate and cobalamin. Fecal alpha1-proteinase inhibitor concentration can
      increase in individuals with excessive GI protein loss. A wide variety of
      inflammatory markers are available for a variety of species that can be used to
      assess the inflammatory activity of various types of inflammatory cells in the GI
      tract, although most of these markers assess neutrophilic inflammation, such as
      neutrophil elastase, calprotectin, or S100A12. N-methylhistamine can serve as a
      marker of mast cell infiltration. Markers for lymphocytic or eosinophilic
      inflammation are currently under investigation. Exocrine pancreatic function can
      be assessed by measurement of serum concentrations of pancreatic lipase
      immunoreactivity (PLI) and trypsin-like immunoreactivity (TLI). Serum PLI
      concentration is increased in individuals with pancreatitis and has been shown to
      be highly specific for exocrine pancreatic function and sensitive for
      pancreatitis. Serum TLI concentration is severely decreased in individuals with
      exocrine pancreatic insufficiency. 

PMID- 24129758
TI  - The colon: from banal to brilliant.
AB  - The colon serves as the habitat for trillions of microbes, which it must
      maintain, regulate, and sequester. This is managed by what is termed the mucosal
      barrier. The mucosal barrier separates the gut flora from the host tissues;
      regulates the absorption of water, electrolytes, minerals, and vitamins; and
      facilitates host-flora interactions. Colonic homeostasis depends on a complex
      interaction between the microflora and the mucosal epithelium, immune system,
      vasculature, stroma, and nervous system. Disruptions in the colonic
      microenvironment such as changes in microbial composition, epithelial cell
      function/proliferation/differentiation, mucus production/makeup, immune function,
      diet, motility, or blood flow may have substantial local and systemic
      consequences. Understanding the complex activities of the colon in health and
      disease is important in drug development, as xenobiotics can impact all segments
      of the colon. Direct and indirect effects of pharmaceuticals on intestinal
      function can produce adverse findings in laboratory animals and humans and can
      negatively impact drug development. This review will discuss normal colon
      homeostasis with examples, where applicable, of xenobiotics that disrupt normal
      function. 

PMID- 24129759
TI  - Diet, genes, and microbes: complexities of colon cancer prevention.
AB  - Colorectal cancer is one of the leading causes of cancer-related deaths in the
      United States, and generally, as countries climb the economic ladder, their rates
      of colon cancer increase. Colon cancer was an early disease where key genetic
      mutations were identified as important in disease progression, and there is
      considerable interest in determining whether specific mutations sensitize the
      colon to cancer prevention strategies. Epidemiological studies have revealed that
      fiber- and vegetable-rich diets and physical activity are associated with reduced
      rates of colon cancer, while consumption of red and processed meat, or alcoholic
      beverages, and overconsumption as reflected in obesity are associated with
      increased rates. Animal studies have probed these effects and suggested
      directions for further refinement of diet in colon cancer prevention. Recently a
      central role for the microorganisms in the gastrointestinal tract in colon cancer
      development is being probed, and it is hypothesized that the microbes may
      integrate diet and host genetics in the etiology of the disease. This review
      provides background on dietary, genetic, and microbial impacts on colon cancer
      and describes an ongoing project using rodent models to assess the ability of
      digestion-resistant starch in the integration of these factors with the goal of
      furthering colon cancer prevention. 

PMID- 24129760
TI  - The development of myelin in the brain of the juvenile rat.
AB  - The development process of myelination varies between region and species. Fully
      myelinated fibers are required if mammalian neural circuits are to function
      normally. Histology samples at staggered time points throughout the study were
      examined at days 4, 5, 7, 8, 10, 14, 17, 24, 37, and 44. We suggest that the
      development of myelin in the juvenile rodent brain can be conveniently separated
      into 3 phases. Evaluation of myelin basic protein-stained sections of the areas
      of brain that contain the elements of the developing limbic system over the
      sensitive period from postnatal day (PND) 14 to 34 may provide an insight into
      possible toxicity that may lead to cognition and learning issues in adults. We
      will hope to develop this notion further in the future. The precise chronology of
      the development of the blood-brain barrier in rats has yet to be established;
      thus, there is potential for significant exposure of the juvenile brain to
      chemicals that do not cross the blood-brain barrier in the adult. Thus, it is
      suggested that evaluation of myelin development should probably be extended to
      all new chemical entities intended for pediatric use, and not just those that are
      intended for central nervous system use. 

PMID- 24129761
TI  - The influence of age on serum concentrations of cardiac troponin I: results in
      rats, monkeys, and commercial sera.
AB  - Cardiac troponins serve as serum biomarkers of myocardial injury. The current
      study examined the influence of age on serum concentrations of cardiac troponin I
      (cTnI). An ultrasensitive immunoassay was used to monitor cTnI concentrations in
      Sprague-Dawley (SD) rats and Erythrocebus patas monkeys of different ages. The
      mean cTnI concentrations were highest in 10-day-old rats compared to 25-, 40-,
      and 80-day-old SD rats. Cardiomyocyte remodeling was apparent in hearts from 10
      day-old SD rats as evident by hypercellularity, irregularly shaped nuclei, and
      moderate numbers of myocytes undergoing mitosis and apoptosis. The mean
      concentration of cTnI in 5 newborn monkeys was considerably higher than that of
      three 1-year-old monkeys. Evidence of cardiomyocyte remodeling was also observed
      in these newborn hearts (loss of myofibrils and cytoplasmic vacuolation).
      Commercial animal serum samples were also analyzed. The concentrations of cTnI
      detected in fetal equine and porcine serum were considerably higher than that
      found in adult equine and porcine serum samples Likewise, fetal bovine serum had
      higher cTnI concentrations (>2,400 pg/ml) than did adult caprine and laprine
      samples (2.5-2.7 pg/ml). The present study found age-related differences in cTnI
      concentrations, with higher levels occurring at younger ages. This effect was
      consistent across several animal species. 

PMID- 24129763
TI  - Detecting secondary structure and surface orientation of helical peptide
      monolayers from resonant hybridization signals.
AB  - Hybridization of dominant vibrational modes with meta-surface resonance allows
      detection of both structural changes and surface orientations of bound helical
      peptides. Depending on the resonance frequency of meta-molecules, a red- or blue-
      shift in peptide Amide-I frequency is observed. The underlying coupling mechanism
      is described by using a temporal coupled mode theory that is in very good
      agreement with the experimental results. This hybridization phenomenon
      constitutes the basis of many nanophotonic systems such as tunable coupled mode
      bio-sensors and dynamic peptide systems driven by infrared signals. 

PMID- 24129764
TI  - CD137 stimulation and p38 MAPK inhibition improve reactivity in an in vitro model
      of glioblastoma immunotherapy.
AB  - Dendritic cell vaccination has become an interesting option for cancer
      immunotherapy. Tumor-lysate-pulsed dendritic cells (DC) can prime naive T cells
      and induce the regression of established tumors including gliomas as shown in
      various animal models. Despite hopeful results even in clinical studies, the
      outcome for many patients is still unsatisfying. In the present study, we tested
      the combination of tumor-lysate-pulsed dendritic cells (TPDC) with a monoclonal
      antibody against CD137, a monoclonal antibody against CD25 (daclizumab) and a
      specific p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) for
      improving immunostimulation in an in vitro model of immunotherapy for human
      gliomas. We observed a higher secretion of interferon gamma by TPDC-primed
      peripheral blood mononuclear cells (PBMC) that were incubated with an antibody
      against CD137 or the p38 MAPK inhibitor. In addition, we observed higher specific
      lysis of tumor cells after incubation of PBMC with the p38 MAPK inhibitor or the
      anti-CD137 antibody. In contrast, incubation of TPDC-primed PBMC with the anti
      CD25 antibody did enhance neither interferon gamma secretion nor cellular
      cytotoxicity. Cell depletion experiments demonstrated that the immune reaction
      induced by TPDC is strongly dependent on CD4-positive and CD8-positive cells.
      Incubation of DC during maturation and antigen loading with the anti-CD137
      antibody did not enhance cytotoxicity and interferon gamma secretion in
      comparison with application of the anti-CD137 antibody during priming. In
      conclusion, our data suggest that p38 MAPK inhibition and anti-CD137 antibodies
      can enhance the immune response against glioblastoma cells.

PMID- 24129765
TI  - Two immune faces of pancreatic adenocarcinoma: possible implication for
      immunotherapy.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human
      neoplasms, having extremely poor prognosis with a 5-year survival rate of <1 %
      and a median survival of 6 months. In contrast to other malignancies, pancreatic
      cancer is highly resistant to chemotherapy and targeted therapy. Therefore, new
      treatment options are urgently needed to improve the survival of patients with
      PDAC. Based on our data showing that patients with higher CD8+ T cell tumour
      infiltration exhibited prolonged overall and disease-free survival compared to
      patients with lower or without CD8+ T cell tumour infiltration, we suggested that
      immunotherapy could be a promising treatment option for PDAC. However, clinical
      data from the chemoradioimmunotherapy with interferon-alpha (IFN) trial did not
      point to an improved efficiency of chemoradiation combined with IFN as compared
      to chemoradiotherapy alone, suggesting an important role of the immune
      suppression induced by PDAC and/or unspecific immune stimulation. In support of
      this hypothesis, we found that the PDAC patients and experimental mice had an
      increased number of regulatory T cells and myeloid-derived suppressor cells.
      These results allowed us to conclude that PDAC provokes not only an anti-tumour
      immune response, but also strong immune suppression. Thus, we supposed that new
      immunotherapeutical strategies should involve not only stimulation of the immune
      system of PDAC patients, but also exert control over the tumour immune
      suppressive milieu. 

PMID- 24129766
TI  - Insulin-like Growth Factor (IGF) system and gastrointestinal stromal tumours
      (GIST): present and future.
AB  - In the last decades, the concept that Insulin-like Growth Factor (IGF) axis plays
      a key role in several steps of tumorigenesis, cancer growth and metastasis has
      been widely documented. The aberration of the IGF system has been described in
      many kinds of tumours, providing several lines of evidence in support of IGF
      receptor type 1 (IGF1R) as molecular target in cancer treatment. Gastrointestinal
      stromal tumors (GIST) are the most common mesenchymal tumor of the
      gastrointestinal tract, commonly characterized in most cases by KIT and PDGFRA
      gain mutations. Beyond to the well recognized KIT and PDGFRA gain mutations, in
      the last years other molecular aberrations have been investigated. Recently,
      several lines of evidence about the involvement of the IGF system in GIST have
      been accumulated. The aim of this review is to report all current data about the
      IGF system involvement in GIST, focusing on the current clinical implication and
      future perspectives.

PMID- 24129768
TI  - Projections from the central amygdaloid nucleus to the precuneiform nucleus in
      the mouse.
AB  - The mouse precuneiform nucleus has been proposed as the midbrain locomotion
      center, a function ascribed to its caudal neighbor, cuneiform nucleus, in the
      rat, cat and other species. The present study investigated the projections from
      the central amygdaloid nucleus to the precuneiform nucleus in the mouse using
      retrograde tracer injections (fluoro-gold) into the precuneiform nucleus and
      anterograde tracer injections (biotinylated dextran amine) into the central
      amygdaloid nucleus. The entire central amygdaloid nucleus except the rostral pole
      had retrogradely labeled neurons, especially in the middle portion where labeled
      neurons were densely packed. Anterogradely labeled amygdaloid fibers approached
      the precuneiform nucleus from the area ventrolateral to it and terminated in the
      entire precuneiform nucleus. Labeled fibers were also found in laminae 5 and 6 in
      the upper cervical cord on the ipsilateral side. The present study is the first
      demonstration of projections from the central amygdaloid nucleus to the
      precuneiform nucleus. This projection may underpin the role of the precuneiform
      nucleus in the modulation of the cardiovascular activity.

PMID- 24129767
TI  - The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific
      sulforhodamine 101-labeling of hippocampal astrocytes.
AB  - Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though
      the labeling mechanism remains unknown and the efficacy of labeling in different
      brain regions is heterogeneous. By combining region-specific isolation of
      astrocytes followed by transcriptome analysis, two-photon excitation microscopy,
      and mouse genetics, we identified the thyroid hormone transporter OATP1C1 as the
      SR101-uptake transporter in hippocampus and cortex. 

PMID- 24129769
TI  - 1D oxide nanostructures from chemical solutions.
AB  - Nanotechnology has motivated a tremendous effort in the synthesis approaches to
      grow free standing or hierarchical nanomaterials such as nanowires and nanorods.
      Bottom-up approaches based on chemistry are an important approach to produce
      nanomaterials, and here the concepts of growing oxide 1D nanostructures from
      chemical solutions are reviewed. The thermodynamic and kinetic aspects of the
      nucleation and growth of oxide compounds in solutions are presented with emphasis
      on hydrothermal and molten salt synthesis. The importance of solubility of
      precursors, the precursor chemistry, role of organic additives as well as the
      chemical complexity and dimensionality and symmetry of the crystal structure of
      the compound grown are highlighted. 

PMID- 24129770
TI  - Aerobic exercise effect on prognostic markers for systolic heart failure
      patients: a systematic review and meta-analysis.
AB  - From previous systematic reviews and meta-analyses, there is consensus about the
      positive effect of exercise training on exercise capacity for systolic heart
      failure (HF); however, the effect on actual prognostic markers such as NTproBNP
      and minute ventilation/carbon dioxide production (VE/VCO2) slope has not been
      evaluated. The primary aim of the proposed study is to determine the effect of
      aerobic exercise training (AEX) on the VE/VCO2 slope and NTproBNP. The following
      databases (up to February 30, 2013) were searched with no language limitations:
      CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE
      (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January
      1929). We screened reference lists of articles and also conducted an extensive
      hand search of the literature. Randomized controlled trials of exercise-based
      interventions with 2-month follow-up or longer compared to usual medical care or
      placebo were included. The study population comprised adults aged between 18 and
      65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and
      baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data
      on study design, participants, interventions, and outcomes. We assessed the risk
      of bias using PEDro scale. We calculated mean differences (MD) or standardized
      mean differences between intervention and control groups for outcomes with
      sufficient data; for other outcomes, we described findings from individual
      studies. Eight studies involving a total of 408 participants met the inclusion
      criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO2 slope (4
      studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a
      MD of -817.75 [95 % confidence interval (CI) -929.31 to -706.19]. Mean
      differences across VE/VCO2 slope were -6.55 (95 % CI -7.24 to -5.87). Those
      patients' characteristics and exercise were similar (frequency = 3-5 times/week;
      duration = 20-50 min/day; intensity = 60-80 % of VO2 peak) on the included
      studies. Moreover, the risk of bias across all studies was homogeneous (PEDro
      scale = 7-8 points). However, based on the statistical analysis, the
      heterogeneity among the studies was still high, which is related to the variable
      characteristics of the studies. Aerobic exercise may be effective at improving
      NTproBNP and the VE/VCO2 slope in systolic HF patients, but these effects are
      limited to a specific HF population meeting specific inclusion criterion in a
      limited number of studies. Future randomized controlled studies including
      diastolic and HF overleap with pulmonary diseases are needed to better understand
      the exact influence of AEX. 

PMID- 24129773
TI  - Racial-ethnic disparities in outpatient mental health visits to U.S. physicians,
      1993-2008.
AB  - OBJECTIVE: The purpose of this study was to examine racial-ethnic differences in
      use of mental health treatment for a comprehensive range of specific disorders
      over time. METHODS: Data from the National Ambulatory Medical Care Survey and the
      National Hospital Ambulatory Medical Care Survey were used to examine adult
      outpatient mental health visits to U.S. physicians from 1993 to 2008 (N=754,497).
      Annual visit prevalence for three racial-ethnic groups was estimated as the
      number of visits divided by the group's U.S. population size. Visit prevalence
      ratios (VPRs) were calculated as the minority group's prevalence divided by the
      non-Hispanic white prevalence. Analyses were stratified by diagnosis, physician
      type, patient characteristics, and year. RESULTS: VPRs for any disorder were .60
      (95% confidence interval [CI]=.52-.68) for non-Hispanic blacks and .58 (CI=.50
      .67) for Hispanics. Non-Hispanic blacks were treated markedly less frequently
      than whites for obsessive-compulsive, generalized anxiety, attention-deficit
      hyperactivity, personality, panic, and nicotine use disorders but more frequently
      for psychotic disorders. Hispanics were treated far less frequently than whites
      for bipolar I, impulse control, autism spectrum, personality, obsessive
      compulsive, and nicotine use disorders but more frequently for drug use
      disorders. Racial-ethnic differences in visits to psychiatrists were generally
      greater than for visits to nonpsychiatrists. Differences declined with increasing
      patient age and appear to have widened over time. CONCLUSIONS: Racial-ethnic
      differences in receipt of outpatient mental health treatment from U.S. physicians
      varied substantially by disorder, provider type, and patient age. Most
      differences were large and did not show improvement over time.

PMID- 24129771
TI  - Inhibition of presynaptic neurotoxins in taipan venom by suramin.
AB  - Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a
      major life-threatening symptom of envenoming by these snakes. Three species of
      taipans exist, and the venom from each species contains a presynaptic neurotoxin
      which accounts for much of the neurotoxicity observed following human envenoming.
      The high cost of antivenom used to treat neurotoxicity has resulted in the need
      to develop alternative but effective therapies. Therefore, in this study, we
      examined the ability of the P2Y receptor antagonist suramin to prevent the in
      vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms:
      taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources
      or purified in house, using multiple steps of gel filtration chromatography. All
      three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer
      cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3
      mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve
      mediated twitches within the course of the experiment (P < 0.0001). However,
      paradoxin induced a 32 % decrease in twitch height even in the presence of
      suramin within 360 min. This was significantly different compared to toxin alone
      (P < 0.0001). We also examined the effect of suramin on the neurotoxic effects of
      textilotoxin and the products of phospholipase A2 action. Each toxin alone or in
      the presence of suramin failed to inhibit the responses to exogenous agonists
      ACh, CCh or KCl. Our results warrant clinical studies aimed determining the
      efficacy of suramin in preventing the onset of neurotoxicity following taipan
      envenoming.

PMID- 24129772
TI  - Three acetophenones from Acronychia pedunculata.
AB  - Phytochemical investigation of the leaves and twigs of Acronychia pedunculata has
      led to the isolation of three new acetophenone monomers 1-3 as well as 1-[2',4'
      dihydroxy-3',5'-di-(3"-methyl-2"-butenyl)-6'-methoxy]phenylethanone (4),
      acronyculatin E (5), a mixture of beta-sitosterol and stigmasterol, and sesamin.
      The structures of these new compounds were elucidated spectroscopically. The
      inhibitory activities of the isolated acetophenone derivatives against mammalian
      DNA polymerases and human cancer cell growth were also assessed. 

PMID- 24129774
TI  - Orthorhombic KSc2F7:Yb/Er nanorods: controlled synthesis and strong red
      upconversion emission.
AB  - For the first time, we have synthesized orthorhombic phase KSc2F7:20%Yb/2%Er
      (KSc2F7:Yb/Er) nanorods and further studied the crystal structure and morphology
      evolution, as well as their upconversion (UC) properties under varying F(-)
      contents and reaction temperatures. Different from beta-NaYF4:20%Yb/2%Er
      (NaYF4:Yb/Er) nanorods that usually give strong green UC luminescence, strong red
      UC emission was observed in KSc2F7:Yb/Er nanorods under 980 nm laser excitation.
      Their UC mechanisms are further analyzed and compared. This study provides a
      novel type of rare earth nanorods with strong red UC emissions which have great
      potential in high resolution 3-dimensional bioimaging, color displays, solid
      state lasers, and photocatalysis. 

PMID- 24129775
TI  - Building social and scientific networks to grow our global skin biology
      community.

PMID- 24129779
TI  - IL36RN mutations in generalized pustular psoriasis: just the tip of the iceberg?
AB  - As IL36RN mutations are a cause of generalized pustular psoriasis (GPP), three
      recent investigations attempted to correlate the IL36RN genotype with GPP
      clinical presentations. These studies found that IL36RN mutations account for
      only a fraction of GPP cases presenting with concomitant psoriasis vulgaris (PV;
      common or typical psoriasis). Pathogenic alleles were also found in control
      populations, indicating that environmental triggers and/or modifier genes may
      contribute to the disease. 

PMID- 24129780
TI  - CXCR4 in epidermal keratinocytes: crosstalk within the skin.
AB  - In this issue, Takekoshi et al. investigated the role of CXCR4 in IL-23-induced
      keratinocyte hyperproliferation using an epidermal-specific knockout mouse model
      and found that CXCR4 limited keratinocyte proliferation. Some reports in the
      literature support this idea, whereas others contradict it; this disparity may be
      related to the differential roles of CXCR4 in various cell types or to a recently
      identified second receptor (CXCR7). Nevertheless, CXCR4 and its ligand SDF-1 have
      been implicated in skin wound healing, systemic lupus erythematosus, and basal
      cell carcinoma tumor angiogenesis. Further study is merited. 

PMID- 24129782
TI  - Organotypic skin culture.

PMID- 24129783
TI  - Prevention and management of non-communicable disease: the IOC consensus
      statement, Lausanne 2013.
AB  - Morbidity and mortality from preventable, non-communicable chronic disease (NCD)
      threatens the health of our populations and our economies. The accumulation of
      vast amounts of scientific knowledge has done little to change this. New and
      innovative thinking is essential to foster new creative approaches that leverage
      and integrate evidence through the support of big data, technology, and design
      thinking. The purpose of this paper is to summarize the results of a consensus
      meeting on NCD prevention sponsored by the International Olympic Committee (IOC)
      in April, 2013. Within the context of advocacy for multifaceted systems change,
      the IOC's focus is to create solutions that gain traction within health care
      systems. The group of participants attending the meeting achieved consensus on a
      strategy for the prevention and management of chronic disease that includes the
      following: 1. Focus on behavioural change as the core component of all clinical
      programs for the prevention and management of chronic disease. 2. Establish
      actual centres to design, implement, study, and improve preventive programs for
      chronic disease. 3. Use human-centered design in the creation of prevention
      programs with an inclination to action, rapid prototyping and multiple
      iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine
      (SEM) professionals to build new programs for the prevention and treatment of
      chronic disease focused on physical activity, diet and lifestyle. 5. Mobilize
      resources and leverage networks to scale and distribute programs of prevention.
      True innovation lies in the ability to align thinking around these core
      strategies to ensure successful implementation of NCD prevention and management
      programs within health care. The IOC and SEM community are in an ideal position
      to lead this disruptive change. The outcome of the consensus meeting was the
      creation of the IOC Non-Communicable Diseases ad-hoc Working Group charged with
      the responsibility of moving this agenda forward. 

PMID- 24129785
TI  - The making of medical ethics.

PMID- 24129784
TI  - Sprint interval training effects on aerobic capacity: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Sprint interval training (SIT) involving repeated 30-s "all out"
      efforts have resulted in significantly improved skeletal muscle oxidative
      capacity, maximal oxygen uptake, and endurance performance. The positive impact
      of SIT on cardiorespiratory fitness has far-reaching health implications.
      OBJECTIVE: The objective of this study was to perform a systematic review of the
      literature and meta-analysis to determine the effects of SIT on aerobic capacity.
      METHODS: A search of the literature was conducted using the key words 'sprint
      interval training', 'high intensity intermittent training/exercise', 'aerobic
      capacity', and 'maximal oxygen uptake'. Seventeen effects were analyzed from 16
      randomized controlled trials of 318 participants. The mean +/- standard deviation
      number of participants was 18.7 +/- 5.1. Participant age was 23.5 +/- 4.3 years.
      RESULTS: The effect size calculated for all studies indicates that supramaximal
      intensity SIT has a small-to-moderate effect (Cohen's d = 0.32, 95 % CI 0.10
      0.55; z = 2.79, P < 0.01) on aerobic capacity with an aggregate improvement of
      ~3.6 mL.kg-1.min-1 (~8 % increase). The effect is moderate to large in comparison
      with no-exercise control groups (Cohen's d = 0.69, 95 % CI 0.46-0.93; z = 5.84, P
      < 0.01) and not different when compared with endurance training control groups
      (Cohen's d = 0.04, 95 % CI -0.17 to 0.24; z = 0.36, P = 0.72). CONCLUSION: SIT
      improves aerobic capacity in healthy, young people. Relative to continuous
      endurance training of moderate intensity, SIT presents an equally effective
      alternative with a reduced volume of activity. This evaluation of effects and
      analysis of moderating variables consolidates the findings of small-sample
      studies and contributes to the practical application of SIT to improve
      cardiorespiratory fitness and health.

PMID- 24129786
TI  - Fifty years of medical ethics: from the London Medical Group to the Institute of
      Medical Ethics.

PMID- 24129787
TI  - The Journal of Medical Ethics and Medical Humanities: offsprings of the London
      Medical Group.

PMID- 24129788
TI  - Harnessing the LMG legacy: the IME's vision for the future.
AB  - London Medical Group was founded in 1963. It was student-led, spawned Medical
      Groups in almost every UK medical school and met a need for non-partisan debate
      and dialogue in medical ethics. It became a victim of its own success as the
      Institute of Medical Ethics published the Pond Report in 1987, which recommended
      that medical ethics be incorporated into the undergraduate curriculum. Medical
      schools began to teach medical ethics and the General Medical Council demanded
      this in 1993's Tomorrow's Doctors. The Institute of Medical Ethics had grown out
      of the LMG. After running a number of successful conferences for medical ethics
      teachers, the Institute of Medical Ethics is recapturing the natural innovative
      tendencies of students and junior doctors that the LMG and related Medical Groups
      had fostered. It is now launching itself as a membership organisation: the
      recommendations of the Francis report and responses to it have emphasised the
      need to support individuals with the ability, freedom and confidence to question
      the status quo from a reasoned ethical basis. The Institute of Medical Ethics
      aims to develop a robust medical ethics community ready to face the challenges of
      21st Century healthcare. 

PMID- 24129789
TI  - Medical humanities: lineage, excursionary sketch and rationale.
AB  - Medical Humanities the journal started life in 2000 as a special edition of the
      JME. However, the intellectual taproots of the medical humanities as a field of
      enquiry can be traced to two developments: calls made in the 1920s for the
      development of multidisciplinary perspectives on the sciences that shed
      historical light on their assumptions, methods and practices; refusals to
      assimilate all medical phenomena to a biomedical worldview. Medical humanities
      the term stems from a desire to situate the significance of medicine as a product
      of culture. But despite growing usage over half a century the term defies a
      unifying encapsulation and continues to conjure up a multitude of discourse
      communities, including scholars working at the interfaces of health and
      humanities, arts and health, and medical education and bioethics. The field is
      intellectually capacious and polymorphous, forming and reforming around critical
      new research questions and teaching tasks spanning disciplines. 

PMID- 24129791
TI  - Controlling helical chirality of cobalt complexes by chirality transfer from
      vicinal diamines.
AB  - Stereoselective cis-trans isomerism of a Co(III)-N2O2 complex has been achieved
      by coordinating chiral vicinal diamines. The induced metal-centered helical
      chirality can be exploited for chirality amplification and asymmetric
      coordination chemistry. 

PMID- 24129792
TI  - A new class of fluorescent-dots: long luminescent lifetime bio-dots self
      assembled from DNA at low temperatures.
AB  - Quantum-dots (QDs) have fuelled up intensive research efforts over the past two
      decades. Nevertheless, currently developed two classes of fluorescent QDs,
      colloidal semiconductor QDs and carbonaceous QDs suffer from either toxicity or
      short luminescence lifetime. Here, we report a new class of fluorescent bio-dots
      that are derived from DNA via self-assembly at low temperatures down to 80
      degrees C, which has an optical bandgap of 3.4 eV, and in particular possesses
      strong photoluminescence with a much longer luminescence lifetime (tau1 = 10.44
      ns) than the carbonaceous QDs (tau1 < 0.5 ns). It is discovered that it is the
      interactions of base pair cytosines with each other to form sp2 carbon-like
      centers as luminescence centers or chromophores for the photoluminescence. The
      use of bio-dots in cell imaging with strong photoluminescence signal and good
      biocompatibility demonstrates great potentials of broad biological and
      optoelectronic applications.

PMID- 24129793
TI  - A guide to the synthesis of block copolymers using reversible-addition
      fragmentation chain transfer (RAFT) polymerization.
AB  - The discovery of reversible-deactivation radical polymerization (RDRP) has
      provided an avenue for the synthesis of a vast array of polymers with a rich
      variety of functionality and architecture. The preparation of block copolymers
      has received significant focus in this burgeoning research field, due to their
      diverse properties and potential in a wide range of research environments. This
      tutorial review will address the important concepts behind the design and
      synthesis of block copolymers using reversible addition-fragmentation chain
      transfer (RAFT) polymerization. RAFT polymerization is arguably the most
      versatile of the RDRP methods due to its compatibility with a wide range of
      functional monomers and reaction media along with its relative ease of use. With
      an ever increasing array of researchers that possess a variety of backgrounds now
      turning to RDRP, and RAFT in particular, to prepare their required polymeric
      materials, it is pertinent to discuss the important points which enable the
      preparation of high purity functional block copolymers with targeted molar mass
      and narrow molar mass distribution using RAFT polymerization. The key principles
      of appropriate RAFT agent selection, the order of monomer addition in block
      synthesis and potential issues with maintaining high end-group fidelity are
      addressed. Additionally, techniques which allow block copolymers to be accessed
      using a combination of RAFT polymerization and complementary techniques are
      touched upon. 

PMID- 24129794
TI  - Internal carotid artery occlusion: its natural history including recanalization
      and subsequent neurological events.
AB  - OBJECTIVE: To determine the incidence of recanalization of the occluded internal
      carotid artery (ICA) and establish its natural history. METHODS: Patients with
      duplex-confirmed ICA occlusions were identified, and a subgroup offered repeat
      scanning. The antemortem condition and cause of death of patients who died were
      recorded. RESULTS: Of 153 patients identified, 77 underwent follow-up at a median
      of 35 months (interquartile range [IQR]: 14-61).In all, 8 (10.3%) demonstrated
      recanalization at a median of 53 months (IQR: 35-114). Of 8, 7 underwent carotid
      endarterectomy with histopathological confirmation of recanalization. Of the 153
      patients, 45 (29%) had further neurological events, and 38 (25%) were within the
      territory of the occluded ICA. In all, 76 patients died, and of the 53 with a
      confirmed cause of death, 12 (23%) were attributed to a cerebrovascular accident
      corresponding to the territory of the occluded artery. CONCLUSION: Recanalization
      of ICA occlusion is common and leads to significant neurological events. Duplex
      ultrasound follow-up appears mandatory.

PMID- 24129795
TI  - Circulatory osmotic desalination driven by a mild temperature gradient based on
      lower critical solution temperature (LCST) phase transition materials.
AB  - Abrupt changes in effective concentration and osmotic pressure of lower critical
      solution temperature (LCST) mixtures facilitate the design of a continuous
      desalination method driven by a mild temperature gradient. We propose a prototype
      desalination system by circulating LCST mixtures between low and high temperature
      (low T and high T) units. Water molecules could be drawn from a high-salt
      solution to the LCST mixture through a semipermeable membrane at a temperature
      lower than the phase transition temperature, at which the effective osmotic
      pressure of the LCST mixture is higher than the high-salt solution. After
      transfer of water to the high T unit where the LCST mixture is phase-separated,
      the water-rich phase could release the drawn water into a well-diluted solution
      through the second membrane due to the significant decrease in effective
      concentration. The solute-rich phase could be recovered in the low T unit via a
      circulation process. The molar mass, phase transition temperature, and aqueous
      solubility of the LCST solute could be tuneable for the circulatory osmotic
      desalination system in which drawing, transfer, release of water, and the
      separation and recovery of the solutes could proceed simultaneously. Development
      of a practical desalination system that draws water molecules directly from
      seawater and produces low-salt water with high purity by mild temperature
      gradients, possibly induced by sunlight or waste heat, could be attainable by a
      careful design of the molecular structure and combination of the circulatory
      desalination systems based on low- and high-molar-mass LCST draw solutes. 

PMID- 24129798
TI  - Intrathoracic anastomotic leakage after gastroesophageal cancer resection is
      associated with reduced long-term survival.
AB  - BACKGROUND: Most likely because of low statistical power, no previous studies
      have shown any significant association between long-term survival and anastomotic
      leakage in patients who have undergone gastroesophageal cancer resection.
      MATERIAL AND METHODS: The present study included, prospectively and
      consecutively, nationwide collected patients who underwent gastroesophageal
      cancer resection between 2003 and 2011 in Denmark. The operation was carried out
      as an Ivor Lewis procedure. Only patients with intrathoracic anastomosis were
      included in the analysis. RESULTS: From 2003 to 2011, 1,296 patients underwent
      gastroesophageal resection, and 128 (9.9 %) of these experienced anastomotic
      leakage. The overall 5-year survival rates in patients with and without
      anastomotic leakage were 20 and 35 % (P < 0.0001), respectively. After exclusion
      of 4 weeks mortality, the 5-year survival rate in patients with leakage was 22 %
      compared to 36 % in patients without anastomotic leakage (P < 0.001). After
      exclusion of 8 weeks mortality, the 5-year survival rate was 23 % in patients
      with leakage and 36 % in those without (P = 0.009). The corresponding median time
      of survival was 74 versus 128, 87 versus 138, and 95 versus 138 weeks,
      respectively. The overall hazard ratios of death after anastomotic leakage,
      unadjusted, and after adjusting for potentially confounding factors, were 1.59
      (1.27-1.99) and 1.45 (1.14-1.84). The unadjusted and adjusted odds ratios after
      exclusion of 4 weeks mortality were 1.51 (1.19-1.90) and 1.41 (1.10-1.81). After
      exclusion of 8 weeks mortality the odds ratios were 1.38 (1.08-1.77) and 1.32
      (1.02-1.71). CONCLUSIONS: This nationwide study confirms that patients
      experiencing anastomotic leakage after gastroesophageal cancer resection have a
      significantly lower long-term survival, even following full recovery after the
      leakage.

PMID- 24129799
TI  - State of the art of robotic pancreatic surgery.
AB  - More than a decade has passed since robotic technology was adopted for abdominal
      surgery, and virtually every gastrointestinal operation has since been shown to
      be feasible, safe, and reproducible using the robotic approach. Robotic
      pancreatic surgery had been left behind at the beginning, because they were
      technically challenging, requiring not only being very familiar with the robotic
      technology but also having a perfect knowledge of the anatomical variations, very
      frequent in this area. Nonetheless in the last few years many authors have
      approached the robot for pancreatic surgery with very promising results in terms
      of surgical and oncological outcomes. The aim of this article is to review the
      literature on robotic pancreatic surgery and to define the state of the art use
      of the robotic approach for pancreatic disease. 

PMID- 24129797
TI  - Differential action of glycoprotein hormones: significance in cancer progression.
AB  - Growth of multicellular organisms depends on maintenance of proper balance
      between proliferation and differentiation. Any disturbance in this balance in
      animal cells can lead to cancer. Experimental evidence is provided to conclude
      with special reference to the action of follicle-stimulating hormone (FSH) on
      Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones
      exert a differential action on their target cells, i.e., stimulate proliferation
      when the cells are in an undifferentiated state which is the situation with
      cancer cells and promote only functional parameters when the cell are fully
      differentiated. Hormones and growth factors play a key role in cell
      proliferation, differentiation, and apoptosis. There is a growing body of
      evidence that various tumors express some hormones at high levels as well as
      their cognate receptors indicating the possibility of a role in progression of
      cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been
      reported to stimulate cell proliferation and act as tumor promoter in a variety
      of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast,
      prostate, etc. This review summarizes evidence to conclude that these hormones
      are produced by some cancer tissues to promote their own growth. Also an attempt
      is made to explain the significance of the differential action of hormones in
      progression of cancer with special reference to prostate cancer. 

PMID- 24129800
TI  - State of the art in robotic hepatobiliary surgery.
AB  - Hepatobiliary (HB) surgery is a challenging surgical subspecialty that requires
      highly specialized training and an adequate level of experience in order to be
      performed safely. As a result, minimally invasive HB surgery has been met with
      slower acceptance as compared to other subspecialties, with many surgeons in the
      field still reluctant to adopt the approach. Recently development of the robotic
      platform has provided a tool that can overcome many of the limitations of
      conventional laparoscopic HB surgery. Augmented dexterity enabled by the
      endowristed movements, software filtration of the surgeon's movements, and high
      definition three-dimensional vision provided by the stereoscopic camera combine
      to allow steady and careful dissection of the liver hilum structures, as well as
      prompt and precise endosuturing in cases of intraoperative bleeding. These
      advantages have fostered many centers to widen the indications for minimally
      invasive HB and gastric surgery, with encouraging initial results. As one of the
      surgical groups that has performed the largest number of robot-assisted
      procedures worldwide, we provide a review of the state of the art in minimally
      invasive robot-assisted HB surgery.

PMID- 24129801
TI  - Value of plasma brain natriuretic peptide levels for predicting postoperative
      atrial fibrillation: a systemic review and meta-analysis.
AB  - BACKGROUND: Blood natriuretic peptide (NP) levels have been reported to be useful
      for predicting postoperative atrial fibrillation (AF). We aimed to quantitatively
      synthesize the current evidence of the accuracy of using NP levels in predicting
      postoperative AF. METHODS AND RESULTS: Medline, Embase, and reference lists were
      searched. Studies were included if either brain natriuretic peptide (BNP) or N
      terminal pro-b type natriuretic peptide (NT-proBNP) had been evaluated
      perioperatively to predict postoperative AF. Data were analyzed to obtain summary
      accuracy estimates. Data from 1,844 patients in 10 studies were analyzed. Summary
      estimates for the sensitivity and specificity of using NP levels for predicting
      postoperative AF were 75 % [95 % confidence interval (CI) 67-79 %] and 80 % (95 %
      CI 62-91 %), respectively. The overall diagnostic odds ratio was 3.28 (95 % CI
      2.23-4.84). Subgroup analysis showed that elevated NP levels in the perioperative
      period were a strong independent predictor of postoperative AF. NT-proBNP
      appeared to have better predictive value than BNP, as did postoperative
      assessment over preoperative assessment. BNP had a better correlation with
      postoperative AF in patients undergoing thoracic surgery than in patients
      undergoing cardiac surgery. CONCLUSIONS: Perioperative assessment of the
      natriuretic peptide level in patients undergoing major cardiothoracic surgery
      could be a valuable diagnostic aid for identifying patients at high risk of
      developing postoperative AF, and for providing critical clinical information to
      guide prophylactic antiarrhythmic therapy in the perioperative period.

PMID- 24129803
TI  - Prevalence of sarcopenia among healthy ambulatory subjects: the sarcopenia begins
      from 45 years.
AB  - BACKGROUND AND AIMS: Sarcopenia has been indicated as a reliable marker of
      frailty and poor prognosis among the oldest individuals. There are only few data
      on sarcopenia in healthy general population. We evaluated the prevalence of
      sarcopenia and its association with functional and clinical status in a
      population of healthy ambulatory subjects over 45 years living at home, in Paris
      (France). METHODS: This study was conducted selecting all ambulatory participants
      (n = 1,445) aged 45 years and older from October 2008 to September 2011,
      consulting in the Institute of Physiology (Institut de Jaeger) from Paris
      (France) for a functional and muscular evaluation, and did not have limitations
      to moderate physical exercise. All were healthy people. All subjects performed a
      medical examination, associated with evaluation of muscle mass (body composition
      assessment using dual-energy X-ray absorptiometry) and of muscle function (by
      hand grip strength). Diagnosis of sarcopenia required the documentation of low
      muscle mass with low muscle strength according to the current international
      consensus definition of sarcopenia. RESULTS: From 1,421 participants (553 males
      and 868 females) definitively enrolled, 221 subjects (135 females and 86 males)
      (15.5 %) were identified as sarcopenic. Results from multivariate logistic
      regression models showed that sarcopenia was inversely associated with BMI with
      those participants with BMI higher than 22 kg/m(2) showing a lower risk of
      sarcopenia relative to those with BMI less than 21 kg/m(2) (OR 0.72; 95 % CI 0.60
      0.91). Similarly, probability of sarcopenia was lower among subjects involved in
      leisure physical activities for 3 h or more per week (OR 0.45; 95 % CI 0.24
      0.93). According to the category of age [45-54; 55-64; 65-74; 75-84 and 85 years
      or more], the prevalence of sarcopenia in women increase from 9.1; 12.7; 14.5;
      19.4; to 33.3 %, respectively. For the men, the percentage of sarcopenia increase
      with aging from 8.6; 15.6; 13.6; 63.8 to 45.5 %, respectively. CONCLUSIONS: The
      present study suggests that among healthy ambulatory subjects over 45 years
      living at home, sarcopenia is frequent, even to the youngest subjects of the
      studied population, taking place from 9 % from 45 years, until 64.3 % for the
      subjects over 85 years. Our findings support the hypothesis that muscle mass and
      function are associated with BMI and physical activity, whatever the age of the
      subject.

PMID- 24129802
TI  - Complications of bronchial stapling in thoracic surgery.
AB  - OBJECTIVE: The use of staplers for thoracic surgery has been widely accepted and
      regarded as a safe procedure. However, complications of stapling are occasionally
      experienced. The aim of this retrospective study was to analyze complications of
      bronchial stapling. METHODS: A retrospective multi-institutional review was
      conducted by the Central Japan Lung Cancer Surgery Study Group, comprising 29
      institutions. All instances of bronchial stapling in thoracic surgery were
      reviewed during the research period. RESULTS: Bronchial stapling was performed
      2,030 times, using 36 kinds of staplers. The total number of complications
      related to stapling was 36 (1.8 %); 31 events occurred intraoperatively and five
      events occurred postoperatively. The intraoperative complications were air
      leakage (N = 20) and stapling failure (N = 11), which were caused by stapler
      tissue thickness mismatch (N = 17), stapler defect (N = 3), tissue fragility (N =
      2), and unknown reasons (N = 9). In all 31 cases, intraoperative complications
      were recovered intraoperatively with additional suturing, and no further
      complications were observed postoperatively. The postoperative complications were
      bronchopleural fistula (BPF) (N = 4) and bleeding from the chest wall
      (intercostal artery) (N = 1). The rate of BPF was 0.2 % (4 of 2,030). Two of four
      BPFs induced critical conditions. Postoperative bleeding was caused by the use of
      Duet TRS(TM). Both total complications and BPF occurred more frequently in the
      main bronchus than in the lobar or segmental bronchus. No relationship was seen
      between the incidence of complications and cartridge colors in lobar bronchial
      stapling. The compression types of staplers were associated with the incidence of
      complication. CONCLUSIONS: Intraoperative and postoperative complications of
      bronchial stapling were studied. Generally, bronchial stapling in recent thoracic
      surgery was safe, but rare postoperative complications may induce critical
      conditions. Knowledge of potential complications and causes of bronchial stapling
      may decrease the incidence of stapling complications.

PMID- 24129804
TI  - Prevalence of vitamin D insufficiency among community dwelling elderly in
      Dakahlia as a representative of rural areas in Egypt.
AB  - BACKGROUND: Vitamin D has a basic role in bone growth and metabolism and has been
      noticed for its important role in many diseases. OBJECTIVES: To detect the
      prevalence of vitamin D insufficiency among the elderly in Dakahlia. METHODOLOGY:
      A cross-sectional study was conducted on 176 elderly patients (60 years and
      older) recruited from Meet Abbad-Nabaroh-Dakahlia, Egypt. The level of 25 hydroxy
      vitamin D (25OHD) was measured. A normal level of vitamin D is defined as a 25OHD
      concentration >=30 ng/mL. Vitamin D insufficiency is defined as a 25OHD
      concentration of 20-29 ng/mL. Vitamin D deficiency is defined as a 25OHD level
      <20 ng/mL. RESULTS: There were no cases of vitamin D deficiency among the studied
      population. The prevalence of vitamin D insufficiency (25OHD level of 20-29
      ng/mL) among the elderly in Dakahlia was 26 %. Prevalence of vitamin D
      insufficiency was (37.9 %) in males and (15.3 %) in females. CONCLUSION: There
      was a low prevalence of vitamin D insufficiency in an elderly rural population
      and a higher prevalence of vitamin D insufficiency among males than females.

PMID- 24129805
TI  - Clinical characteristics, treatment patterns and survival outcome of
      hepatocellular carcinoma patients aged 70 years or older: a single-center
      retrospective study from China.
AB  - BACKGROUND AND AIMS: The information about clinical presentation and outcome of
      elderly hepatocellular carcinoma (HCC) patients is limited. We performed this
      study to assess the impact of age on potential differences in clinical
      characteristics, treatment patterns and outcome in HCC patients. METHODS:
      Clinical data of 164 "elderly" (>=70 years old) and 531 "younger" (<70 years old)
      HCC patients treated at a Chinese tertiary university-affiliated medical center
      between April 2004 and April 2012 were collected and compared using various
      parameters. RESULTS: Compared with younger patients, the elderly patients had a
      higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B
      virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus
      (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs.
      76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no
      significant difference between the two groups in Child-Pugh class and tumor
      stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %,
      p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger
      patients. The overall survival was not significantly different between the two
      groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION: Characteristics that
      distinguish elderly from younger HCC patients included more female, less HBV
      infection, more HCV infection, less liver cirrhosis and massive tumors.
      Significant differences were observed in therapeutic strategies utilized with the
      two groups, but the overall survival was not significantly different.

PMID- 24129806
TI  - Enhanced fidelity to treatment for bipolar disorder: results from a randomized
      controlled implementation trial.
AB  - OBJECTIVE: The authors compared fidelity to bipolar disorder treatment at
      community practices that received a standard or enhanced version of a novel
      implementation intervention called Replicating Effective Programs (REP). METHODS:
      Five community practices in Michigan and Colorado were assigned at random to
      receive enhanced (N=3) or standard (N=2) REP to help implement Life Goals
      Collaborative Care (LGCC), a psychosocial intervention consisting of four self
      management support group sessions, ongoing care management contacts by phone, and
      dissemination of guidelines to providers. Standard REP includes an intervention
      package consisting of an outline, a treatment manual and implementation guide, a
      standard training program, and as-needed technical assistance. Enhanced REP added
      customization of the treatment manual and ongoing, proactive technical assistance
      from internal and external facilitators. Multiple and logistic regression
      analyses determined the impact of enhanced versus standard REP on patient-level
      fidelity. RESULTS: The participants (N=384) had a mean age of 42 years; 67% were
      women, and 30% were nonwhite. Participants attended an average of three group
      sessions and had an average of four care management contacts. After adjustment
      for patient factors, enhanced REP was associated with 2.6 (p<.001) times more
      total sessions and contacts than standard REP, which was driven by 2.5 (p<.01)
      times more care management contacts. Women and participants with a history of
      homelessness had fewer total sessions and contacts. CONCLUSIONS: Enhanced REP was
      associated with improved LGCC fidelity, primarily for care management contacts.
      Additional customization of interventions such as LGCC may be needed to ensure
      adequate treatment fidelity for vulnerable populations.

PMID- 24129807
TI  - Interleukin-18 promoter polymorphisms and plasma levels are associated with
      increased risk of periodontitis: a meta-analysis.
AB  - OBJECTIVE: Emerging evidence has showed that interleukin-18 (IL-8) promoter
      polymorphisms and plasma IL-18 levels may be associated with increased risk of
      periodontitis, but individually published results are inconclusive. The aim of
      this meta-analysis was to derive a more precise estimation of these associations.
      METHODS: A literature search of PubMed, Cochrane Library, Embase, Web of Science,
      SpringerLink, China BioMedicine and China National Knowledge Infrastructure
      databases was conducted on articles published before April 1st, 2013. Crude odds
      ratio (OR) or standardized mean difference (SMD) with 95 % confidence intervals
      (CI) were calculated. RESULTS: Nine case-control studies were included with a
      total of 576 periodontitis patients and 458 healthy controls. Two common
      polymorphisms (-607A > C and -137G>C) in the IL-18 gene were addressed. Our meta
      analysis results indicated that the C variant of IL-18 -607A>C polymorphism was
      associated with increased periodontitis risk (C allele vs. A allele: OR = 1.86,
      95 % CI: 1.30-2.65, P = 0.001; AC+CC vs. AA: OR = 2.64, 95 % CI: 1.34-5.21, P =
      0.005). There was also a significant association between the C variant of IL-18 
      137G>C polymorphism and an increased periodontitis risk (C allele vs. G allele:
      OR = 1.47, 95 % CI: 1.13-1.91, P = 0.004; GC+CC vs. GG: OR = 1.66, 95 % CI: 1.21
      2.29, P = 0.002). Furthermore, the mean levels of plasma IL-18 of periodontitis
      patients were also higher than those of healthy controls (SMD = 1.18, 95 % CI:
      0.51-1.85, P = 0.001). CONCLUSION: The current meta-analysis suggests that IL-18
      promoter polymorphisms and plasma IL-18 levels are associated with increased risk
      of periodontitis. IL-18 promoter polymorphisms and elevated plasma IL-18 levels
      may be useful biomarkers for predicting the development of periodontitis.

PMID- 24129808
TI  - Instantly switchable adhesion of bridged fibrillar adhesive via gecko-inspired
      detachment mechanism and its application to a transportation system.
AB  - Inspired by the exceptional climbing ability of gecko lizards, artificial
      fibrillar adhesives have been extensively studied over the last decade both
      experimentally and theoretically. Therefore, a new leap towards practical uses
      beyond the academic horizon is timely and highly anticipated. To this end, we
      present a fibrillar adhesive in the form of bridged micropillars and its
      application to a transportation system with the detachment mechanism inspired by
      the climbing behaviour of gecko lizards. The adhesive shows strong normal
      attachment (~30 N cm(-2)) as well as easy and fast detachment within 0.5 s
      without involving complex dynamic mechanisms or specific stimulus-responsive
      materials. The fabrication of the bridged micropillars consists of replica
      moulding of polydimethylsiloxane (PDMS) micropillars, transfer of the PDMS
      precursor to the heads of the micropillars, and inverse placement on an inert
      Teflon-coated surface. Owing to the spontaneous interconnections of low viscosity
      PDMS precursor, bridged micropillars with a uniform capping nanomembrane (~800 nm
      thickness) are formed over a large area. Interestingly, macroscopic adhesion in
      the normal direction can be immediately switched between on and off states by
      changing the two detachment modes of pulling and peeling, respectively. To prove
      the potential of the fibrillar adhesive for practical use, an automated
      transportation system is demonstrated for lifting and releasing a mass of stacked
      glass slides over 1000 cycles of attachment and detachment.

PMID- 24129809
TI  - Impact of adding cisplatin to S-1 in elderly patients with advanced gastric
      cancer.
AB  - PURPOSE: We retrospectively examined the efficacy and safety of S-1 alone or S-1
      plus cisplatin (SP) for elderly patients with advanced gastric cancer because the
      benefit of adding cisplatin in these patients still remains unclear. PATIENTS AND
      METHODS: Among 175 patients aged 70 years or older who received S-1 alone or SP
      as a first-line therapy between April 2000 and November 2010 at our institution,
      104 patients who met eligibility criteria were examined. We investigated safety
      and efficacy of S-1 and SP. RESULTS: Among these 104 patients, 73 patients
      received S-1 and 31 patients received SP. The median age was 75 years in the S-1
      group and 74 years in the SP group. The response rate was 26.3 % in the S-1 group
      and 44.0 % in the SP group. Major grade 3 or higher adverse events were observed
      as follows (S-1 vs. SP): nausea (1.4 vs. 16.1 %), anorexia (16.4 vs. 41.9 %),
      neutropenia (4.1 vs. 35.5 %), and febrile neutropenia (0 vs. 9.7 %). The median
      overall survival (OS) was 10.4 months in the S-1 group and 17.8 months in the SP
      group. Treatment of SP and histology of intestinal type were detected as
      independent, good prognostic factors in multivariate analysis. CONCLUSION: SP
      might improve OS with some added toxicity compared to S-1 alone in elderly
      patients with advanced gastric cancer.

PMID- 24129810
TI  - Decreasing the supply of and demand for guns: Oakland's Youth Advocacy Project.
AB  - This paper is a case study of how Youth ALIVE!, a nonprofit public health
      organization, blended direct service and policy goals to reduce youth gun
      violence at a time when guns became the number one killer of children in
      California. Youth ALIVE! trained young people living in California communities
      with the highest rates of gun violence to become peer educators and leaders to
      reduce both the supply of, and demand for, guns. The youth presented health and
      criminal justice data in the context of their own experiences living in
      communities endangered by gun violence to help build public policy solutions,
      contributing to the subsequent drop in gun homicides. Youth ALIVE's vibrant
      grassroots model provides a real-life tableau of research and direct services
      working together to yield realistic policy solutions to a lethal public health
      problem. The youths' successes demonstrate how nonprofit direct service
      organizations are uniquely positioned to advocate for policy and regulatory
      changes that can be beneficial to both program participants and society. Direct
      service organizations' daily exposure to real-life client needs provides valuable
      insights for developing viable policies-plus highly motivated advocates. When
      backed by scientific findings on the causes of the problem, this synergy of youth
      participant engagement in civil society can promote good policy and build healthy
      communities. 

PMID- 24129811
TI  - Future innovation and research in dental restorative materials.

PMID- 24129812
TI  - The challenge for innovation in direct restorative materials.
AB  - During the past 50 years, a series of key UN conferences have established a
      framework to minimize human health risks from environmental exposures to key
      chemicals. In January 2013, more than 140 countries agreed to the text of new
      treaty to minimize Hg effects on the environment (the Minamata Convention).
      Dental caries is omnipresent around the globe, affecting 60% to 90% of school
      children and most adults, and producing discomfort that affects quality of life.
      Dental amalgam is frequently used to treat carious lesions and its use releases
      mercury into the environment. The best way to avoid the use of dental amalgam is
      to emphasize caries prevention. Alternatives to amalgam are suitable in some
      applications, but no replacement for amalgam has been found for large posterior
      restorations. For any restorative material, safety and environmental impacts are
      part of clinical risk assessment. Safety is freedom from unacceptable risks. Risk
      is a combination of probability of exposure and severity of harm. Best management
      practices are crucial to manage dental amalgam, but these impose additional that
      are disproportionately more for developing countries. The Minamata Convention
      seeks a phase-out of all mercury-based products except dental amalgam, where a
      phase-down is the present goal. For dentistry, the most important focus is the
      promotion of caries prevention and research on new materials. 

PMID- 24129813
TI  - What constitutes an ideal dental restorative material?
AB  - Intense environmental concerns recently have prompted dentistry to evaluate the
      performance and environmental impact of existing restoration materials. Doing so
      entices us to explore the 'what if?' innovation in materials science to create
      more ideal restorative materials. Articulating a specification for our design and
      evaluation methods is proving to be more complicated than originally anticipated.
      Challenges exist not only in specifying how the material should be manipulated
      and perform clinically but also in understanding and incorporating implications
      of the skill of the operator placing the restoration, economic considerations,
      expectations patients have for their investment, cost-effectiveness, influences
      of the health care system on how and for whom restorations are to be placed, and
      global challenges that limit the types of materials available in different areas
      of the world. The quandary is to find ways to actively engage multiple
      stakeholders to agree on priorities and future actions to focus future directions
      on the creation of more ideal restorative materials that can be available
      throughout the world. 

PMID- 24129815
TI  - Incorporating new materials and techniques into clinical practice.
AB  - This article outlines the subjects presented and discussed at the December 2012
      IADR Dental Materials Innovation Workshop held at King's College London.
      Incorporating new materials and techniques into clinical practice was considered
      from 4 perspectives: (1) Accelerating the "research to regulatory approval"
      process was presented with current developments in the United States, with the
      National Institutes of Health/Food and Drug Administration process as a working
      example; (2) intellectual property and regulatory requirements were discussed
      across the well-established US and EU frameworks, as well as the more recently
      developed procedures across Brazil, Russia, India, and China; (3) the challenges
      and opportunities of incorporating innovations into dental education were
      considered with reference to the future needs of both students and faculty; and
      (4) the key but difficult and unpredictable step of translating such innovations
      into routine dental practice was then explored. Constructive and far-ranging
      discussion among the broadly based Workshop participants (from dental research,
      education, practice, and industry, as well as environmental organizations and the
      World Health Organization) mapped out key issues for the future. The focus was on
      facilitating the more timely adoption of improvements in both materials and
      techniques to improve patient health and health systems, while minimizing
      environmental impact. 

PMID- 24129814
TI  - Outside-the-(cavity-prep)-box thinking.
AB  - Direct placement restorative materials must interface with tooth structures that
      are often compromised by caries or trauma. The material must seal the interface
      while providing sufficient strength and wear resistance to assure function of the
      tooth for, ideally, the lifetime of the patient. Needed are direct restorative
      materials that are less technique-sensitive than current resin-based composite
      systems while having improved properties. The ideal material could be
      successfully used in areas of the world with limited infrastructure. Advances in
      our understanding of the interface between the restoration adhesive system and
      the stages of carious dentin can be used to promote remineralization. Application
      of fracture mechanics to adhesion at the tooth-restoration interface can provide
      insights for improvement. Research in polymer systems suggests alternatives to
      current composite resin matrix systems to overcome technique sensitivity, while
      advances in nano- and mesoparticle reinforcement and alignment in composite
      systems can increase material strength, toughness, and wear resistance,
      foreshadowing dental application. 

PMID- 24129816
TI  - Ensuring the global availability of high-quality dental restorative materials.
AB  - The Minamata Convention, a global legally binding instrument (treaty) on mercury,
      has been the catalyst for the emerging agenda on global dental materials
      research. If the current and future challenges of oral health maintenance and
      healing on a global scale are to be met, a logical and effective research agenda
      for the discovery and introduction of new, environmentally sustainable, dental
      materials must be developed through a coordinated effort involving materials
      scientists, dental clinicians, representatives of industry, members of regional
      and national regulatory bodies, and advocacy from research organizations. For
      universal impact, this agenda should be created with awareness of several
      important ongoing initiatives, such as the WHO non-communicable diseases action
      plan, the UN sustainable development agenda, and the IADR Global Oral Health In
      Inequalities Research Agenda (GOHIRA). A significant contributor to this cause is
      the FDI and its membership, who, through their Vision 2020 initiative,
      acknowledge their role and responsibility in globally preventing and managing
      dental disease and providing leadership to the profession in terms of information
      dissemination and affecting change. Dental researchers also have an obligation to
      advocate for appropriate funding to match the identified research needs, thus
      enhancing the possibility that key decision-makers will provide the needed
      support to achieve the research agenda agreed upon by this diverse group of
      stakeholders. 

PMID- 24129817
TI  - Priorities for future innovation, research, and advocacy in dental restorative
      materials.
AB  - Innovations in materials science, both within and outside of dentistry, open
      opportunities for the development of exciting direct restorative materials. From
      rich dialog among experts from dental and non-dental academic institutions and
      industry, as well as those from policy, research funding, and professional
      organizations, we learned that capitalizing on these opportunities is
      multifactorial and far from straightforward. Beginning from the point when a
      restoration is needed, what materials, delivery systems, and skills are needed to
      best serve the most people throughout the world's widely varied economic and
      infrastructure systems? New research is a critical element in progress. Effective
      advocacy can influence funding and drives change in practice and policy. Here we
      articulate both research and advocacy priorities, with the intention of focusing
      the energy and expertise of our best scientists on making a difference, bringing
      new innovations to improve oral health. 

PMID- 24129818
TI  - Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic
      epithelial cell clusters.
AB  - We showed previously that proliferating human islet-derived de-differentiated
      cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed
      DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial
      transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs
      can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT)
      by re-addition of mammalian sera. In this study, we show that platelet-derived
      growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal
      accompanied by accumulation of cytoplasmic beta-catenin and a decrease in the
      levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced
      dispersal of ECCs is a more general phenomenon that occurs also with bone marrow
      mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs,
      and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the
      Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473
      phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially
      inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R)
      antagonist JNJ-10198409 inhibited both PDGF-BB--and serum-induced ECC dispersal.
      Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway,
      did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data
      suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the
      activation of the PI3K-Akt pathway.

PMID- 24129819
TI  - Tissue engineering airway mucosa: a systematic review.
AB  - OBJECTIVES/HYPOTHESIS: Effective treatments for hollow organ stenosis, scarring,
      or agenesis are suboptimal or lacking. Tissue-engineered implants may provide a
      solution, but those performed to date are limited by poor mucosalization after
      transplantation. We aimed to perform a systematic review of the literature on
      tissue-engineered airway mucosa. Our objectives were to assess the success of
      this technology and its potential application to airway regenerative medicine and
      to determine the direction of future research to maximize its therapeutic and
      commercial potential. DATA SOURCES AND REVIEW METHODS: A systematic review of the
      literature was performed searching Medline (January 1996) and Embase (January
      1980) using search terms "tissue engineering" or "tissue" and "engineering" or
      "tissue engineered" and "mucous membrane" or "mucous" and "membrane" or "mucosa."
      Original studies utilizing tissue engineering to regenerate airway mucosa within
      the trachea or the main bronchi in animal models or human studies were included.
      RESULTS: A total of 719 papers matched the search criteria, with 17 fulfilling
      the entry criteria. Of these 17, four investigated mucosal engineering in humans,
      with the remaining 13 studies investigating mucosal engineering in animal models.
      The review demonstrated how an intact mucosal layer protects against infection
      and suggests a role for fibroblasts in facilitating epithelial regeneration in
      vitro. A range of scaffold materials were used, but no single material was
      clearly superior to the others. CONCLUSION: The review highlights gaps in the
      literature and recommends key directions for future research such as epithelial
      tracking and the role of the extracellular environment.

PMID- 24129820
TI  - Toward the discovery of inhibitors of babesipain-1, a Babesia bigemina cysteine
      protease: in vitro evaluation, homology modeling and molecular docking studies.
AB  - Babesia bigemina is a protozoan parasite that causes babesiosis, a disease with a
      world-wide distribution in mammals, principally affecting cattle and man. The
      unveiling of the genome of B. bigemina is a project in active progress that has
      already revealed a number of new targets with potential interest for the design
      of anti-babesiosis drugs. In this context, babesipain-1 has been identified as a
      proteolytically active enzyme whose three-dimensional structure has not been
      resolved yet, but which is known to be inhibited by cysteine proteases inhibitors
      such as E64, ALLN, leupeptin, and vinyl sulfones. In this work, we introduce (1)
      a homology model of babesipain-1; (2) a comparison between babesipain-1 and
      falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum;
      (3) in vitro data for babesipain-1 inhibition by HEDICINs and HECINs, previously
      reported as modest inhibitors of falcipain-2; and (4) the docked binding
      conformations of HEDICINs and HECINs in the model of babesipain-1. HEDICINs
      presented similar preferred binding conformations for both babesipain-1 and
      falcipain-2. However, in vitro bioassay shows that HEDICINs and HECINs are better
      inhibitors of babesipain-1 than of falcipain-2, which could be explained by
      observed differences between the active pockets of these proteins in silico.
      Results presented herein provide a valuable contribution to future computer-aided
      molecular design of new babesipain-1 inhibitors. 

PMID- 24129821
TI  - Palladium catalyzed dehydrogenative arylation of coumarins: an unexpected switch
      in regioselectivity.
AB  - A new regioselective alpha-arylation of coumarins with unactivated simple arenes
      via a palladium-catalyzed twofold C-H functionalization is devised. This method
      offers an attractive new approach to synthesis of a wide variety of 3
      arylcoumarins from readily accessible starting materials. 

PMID- 24129823
TI  - How do spin waves pass through a bend?
AB  - Spin-wave devices hold great promise to be used in future information processing.
      Manipulation of spin-wave propagation inside the submicrometer waveguides is at
      the core of promoting the practical application of these devices. Just as in
      today's silicon-based chips, bending of the building blocks cannot be avoided in
      real spin-wave circuits. Here, we examine spin-wave transport in bended magnonic
      waveguides at the submicron scale using micromagnetic simulations. It is seen
      that the impact of the bend is relevant to the frequency of the passing spin
      wave. At the lowest frequencies, the spin wave continuously follows the waveguide
      in the propagation process. At the higher frequencies, however the bend acts as a
      mode converter for the passing spin wave, causing zigzag-like propagation path
      formed in the waveguide behind the bend. Additionally, we demonstrate a logic-NOT
      gate based on such a waveguide, which could be combined to perform logic-NAND
      operation. 

PMID- 24129822
TI  - A peptide derived from TIMP-3 inhibits multiple angiogenic growth factor
      receptors and tumour growth and inflammatory arthritis in mice.
AB  - The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2
      (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in
      the angiogenic pathway. Inhibition of this interaction is proving of value in
      moderating the neovascularization accompanying age-related macular degeneration
      and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3)
      has been shown to be a natural VEGFR-2 specific antagonist-an activity that is
      independent of its ability to inhibit metalloproteinases. In this investigation
      we localize this activity to the C-terminal domain of the TIMP-3 molecule and
      characterize a short peptide, corresponding to part of this domain, that not only
      inhibits all three VEGF-family receptors, but also fibroblast growth factor and
      platelet-derived growth factor receptors. This multiple-receptor inhibition may
      explain why the peptide was also seen to be a powerful inhibitor of tumour growth
      and also a partial inhibitor of arthritic joint inflammation in vivo. 

PMID- 24129824
TI  - Safety and efficacy of portal vein embolization before planned major or extended
      hepatectomy: an institutional experience of 358 patients.
AB  - INTRODUCTION: Portal vein embolization (PVE) stimulates hypertrophy of the future
      liver remnant (FLR) and may improve the safety of extended hepatectomy. The
      efficacy of PVE was evaluated. METHODS: Records of 358 consecutive patients who
      underwent PVE before intended major hepatectomy at our institution from 1995
      through 2012 were retrospectively reviewed. RESULTS: One hundred twelve patients
      (31.3 %) had right PVE alone; 235 (65.6 %) had right PVE plus segment IV
      embolization. The first-session PVE completion rate was 97.8 %. The PVE
      complication rate was 3.9 %. The median pre-PVE and post-PVE standardized FLRs
      were 19.5 % (interquartile range, 15.0-25.9) and 29.7 % (interquartile range,
      22.5-38.2), respectively. Two hundred forty patients (67.0 %) underwent
      potentially curative resection. Sixty-two patients (25.8 %) had major post
      hepatectomy complications; rates of postoperative hepatic insufficiency and 90
      day liver-related mortality were 8.3 and 3.8 %, respectively. The proportion of
      patients with colorectal liver metastasis increased from 38.6 % before 2005 to
      78.2 % in 2010-2012. Despite increased use of preoperative chemotherapy,
      postoperative hepatic insufficiency and 90-day liver-related mortality rates
      dropped from 10.6 and 4.1 %, respectively, before 2010 to 2.9 and 2.9 %,
      respectively, in 2010-2012. CONCLUSIONS: PVE can be safely performed with minimal
      morbidity. Most patients can proceed to extended hepatectomy, which is associated
      with a minimal mortality rate.

PMID- 24129825
TI  - Morbidity and mortality after pancreaticoduodenectomy in patients with borderline
      resectable type C clinical classification.
AB  - BACKGROUND: We previously described the clinical classification of patients with
      resectable pancreatic tumor anatomy but marginal performance status (PS) or
      reversible comorbidities as "borderline resectable type C" (BR-C). This study was
      designed to analyze the incidence and risk factors for post
      pancreaticoduodenectomy (PD) morbidity/mortality in a multi-institutional cohort
      of BR-C patients. METHODS: Elective PDs were evaluated from the 2005-10 ACS-NSQIP
      database. BR-C was defined as age >= 80, poor PS, weight loss > 10 %, pulmonary
      disease, recent myocardial infarction/angina, stroke history, and/or preoperative
      sepsis. Variables associated with 30-day postoperative major complications (PMC)
      and mortality were analyzed. RESULTS: A total of 3,033/8,266 (36.7 %) patients
      were BR-C. BR-C patients were more likely to suffer PMC (31.3 vs. 26.2 %) and
      mortality (4.1 vs. 2.3 %). BR-C patients with PMC suffered 50 % higher mortality
      versus non-BR-C patients with PMC (11.5 vs. 7.7 %) (all p < 0.001). For BR-C
      patients, multivariate analysis identified the following risk factors for PMC or
      mortality: albumin < 3.5 g/dL, dyspnea, preoperative sepsis, age >= 80, poor PS,
      anesthesia score >= 4, and intraoperative transfusion >= 4 units. CONCLUSIONS:
      Nationwide, one third of patients undergoing PD are medically borderline. These
      BR-C patients are at higher risk for and less able to be rescued from PMC.
      Surgeons should identify and optimize comorbidities and utilize prehabilitation
      to address functional deficits before elective PD.

PMID- 24129826
TI  - Radiographic tumor-vein interface as a predictor of intraoperative, pathologic,
      and oncologic outcomes in resectable and borderline resectable pancreatic cancer.
AB  - BACKGROUND: Venous resection may be required to achieve complete resection of
      pancreatic cancers. We assessed the ability of radiographic criteria to predict
      the need for superior mesenteric-portal vein (SMV-PV) resection and the presence
      of histologic vein invasion. METHODS: All patients who underwent
      pancreaticoduodenectomy from 2004 to 2011 at the authors' institution were
      identified. Preoperative pancreatic protocol CT images were re-reviewed to
      characterize the extent of tumor-vein circumferential interface (TVI) as
      demonstrating no interface, <= 180 degrees  of vessel circumference, >180 degrees
      of vessel circumference, or occlusion. Findings were correlated with the need
      for venous resection, histologic venous invasion, and survival. RESULTS: A total
      of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98
      (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received
      neoadjuvant chemoradiation. The TVI classification system predicted with fair
      accuracy both the need for SMV-PV resection at the time of surgery and histologic
      invasion of the vein. In particular, 89.5 % of patients with TVI > 180 degrees 
      or occlusion required SMV-PV resection. Of those, 82.4 % had documented
      histologic SMV-PV invasion. TVI <= 180 degrees  was associated with favorable
      overall survival compared to a greater circumferential interface. CONCLUSIONS: A
      tomographic classification of the tumor-SMV-PV interface can predict the need for
      venous resection, pathologic venous involvement, and survival. To assist in
      treatment planning, a standardized assessment of this anatomic relationship
      should be routinely performed.

PMID- 24129827
TI  - High-resolution manometry classifications for idiopathic achalasia in patients
      with Chagas' disease esophagopathy.
AB  - BACKGROUND: Idiopathic achalasia (IA) and Chagas' disease esophagopathy (CDE)
      share several similarities. The comparison between IA and CDE is important to
      evaluate whether treatment options and their results can be accepted universally.
      High-resolution manometry (HRM) has proved a better diagnostic tool compared to
      conventional manometry. This study aims to evaluate HRM classifications for
      idiopathic achalasia in patients with CDE. METHODS: We studied 98 patients: 52
      patients with CDE (52 % females, mean age, 57 +/- 14 years) and 46 patients with
      IA (54 % females; mean age 48 +/- 19 years). All patients underwent a HRM and
      barium esophagogram. RESULTS: The Chicago classification was distributed in IA as
      Chicago I, 35 %; Chicago II, 63 %; and Chicago III, 2 %, and in CDE as Chicago I,
      52 %; Chicago II, 48 %; and Chicago III, 0 % (p = 0.1, 0.1, and 0.5,
      respectively). All patients had the classic Rochester type. CDE patients had more
      pronounced degrees of esophageal dilatation (p < 0.002). The degree of esophageal
      dilatation did not correlate with Chicago classification (p = 0.08). In nine (9
      %) patients, the HRM pattern changed during the test from Chicago I to II.
      CONCLUSION: Our results show that (a) HRM classifications for IA can be applied
      in patients with CDE and (b) HRM classifications did not correlate with the
      degree of esophageal dilatation. HRM classifications may reflect esophageal
      repletion and pressurization instead of muscular contraction. The correlation
      between manometric findings and treatment outcomes for CDE needs to be answered
      in the near future.

PMID- 24129828
TI  - Prognostic impact of lymph node retrieval and ratio in gastric cancer: a U.S.
      single center experience.
AB  - INTRODUCTION: Increased lymph node (LN) retrieval for gastric cancer has been
      associated with improved overall survival (OS). This study examines the impact of
      number of examined LN (eLN) and lymph node ratio. METHODS: Patients referred for
      surgical care of gastric cancer were stratified by number of eLN, positive LNs
      (LN+), and lymph node ratio (LN+/eLN). Clinicopathologic factors were compared;
      OS and disease-free survival (DFS) were the primary endpoints. RESULTS: From 1997
      to 2012, 222 patients, median age 67 (range, 17-92) years, were analyzed. Of 220
      (99 %) explored, 164 (74 %) underwent resection. Median OS was 22 (range, 0.3
      140) months. Perineural and lymphovascular invasion and poor differentiation
      adversely affected OS, p < 0.05. A median 14 eLN (range, 0-45), with median 1 LN+
      (range, 0-31), was observed. There were no OS or DFS differences when comparing
      the eLN groups. Both OS and DFS were impacted by LN+. Lymph node ratio
      demonstrated worse median OS with increasing ratio: 49 months (0) to 37 months
      (0.01-0.2), 27 months (0.21-0.5), and 12 months (>0.5), p < 0.0001. DFS was
      similar: 35 months (0), decreasing to 22 months (0.01-0.2), 13 months (0.21-0.5),
      and 7 months (>0.5), p < 0.0001. CONCLUSION: Number of eLN did not impact
      survival, while LN+ adversely affected survival. Lymph node ratio may predict
      prognosis better than number of eLN or LN+ in gastric cancer.

PMID- 24129830
TI  - Delayed left ventricular-to-right atrial communication (acquired Gerbode defect)
      after aortic valve replacement.

PMID- 24129829
TI  - Pharmacologic prophylaxis, postoperative INR, and risk of venous thromboembolism
      after hepatectomy.
AB  - INTRODUCTION: Pharmacologic prophylaxis (PP) is recommended for patients
      undergoing general surgical procedures with at least moderate risk of venous
      thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is
      controversial, however, due to concerns regarding postoperative liver dysfunction
      and bleeding. METHODS: We conducted a retrospective analysis of a prospectively
      maintained institutional database in order to clarify the relationship between
      PP, postoperative INR, and risk of VTE. RESULTS: Postoperative VTE occurred in 55
      of 2,147 patients (2.6 %) and was independently associated with advanced age,
      higher BMI, longer procedure time, and development of a major complication, as
      well as higher postoperative INR (>=1.5 versus <1.5: OR 2.50, P = 0.006).
      Patients undergoing more extensive liver resection with higher postoperative INR
      were less likely to receive PP, but receipt of PP demonstrated no relationship
      with either VTE incidence or hemorrhagic complications. CONCLUSIONS: In this
      large single-institution study, incidence of VTE was not associated with PP but
      was associated with higher postoperative INR, contrary to the notion that
      postoperative liver dysfunction is protective against VTE. The interplay between
      prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be
      more completely characterized before broad recommendations can be made regarding
      PP use in these patients.

PMID- 24129832
TI  - 3-D PLLA scaffolds formation by a supercritical freeze extraction assisted
      process.
AB  - Various techniques have been reported in the literature for the fabrication of
      biodegradable scaffolds; but, it is very difficult to obtain in the same
      structure macro, micro and nanostructural characteristics. In this work we
      developed a supercritical freeze extraction process (SFEP) for the formation of
      poly(L-lactic acid) (PLLA) scaffolds, that combines the advantages of thermally
      induced phase separation with those of supercritical drying. We processed
      solutions in chloroform of two PLLA molecular weights and at different polymer
      concentrations ranging between 5 and 20 % w/w. Supercritical drying was performed
      at 35  degrees Cand pressures ranging between 100 and 250 bar. 3-D scaffolds
      characterized by high porosity (between 88 and 97.5 %), with coexisting micro and
      nanometric morphology were obtained. Structures generated were characterized by
      pores ranging between 10 and 30 MUm and with a wrinkled nanostructure of about
      200 nm, superimposed on the internal pore surface, that could be useful for
      biomedical applications. A solvent residue lower than 5 ppm was also measured. 

PMID- 24129831
TI  - Genome-wide methylation profiling of ADPKD identified epigenetically regulated
      genes associated with renal cyst development.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic
      disease characterized by the formation of multiple fluid-filled cysts in
      bilateral kidneys. Although mutations in polycystic kidney disease 1 (PKD1) are
      predominantly responsible for ADPKD, the focal and sporadic property of
      individual cystogenesis suggests another molecular mechanism such as epigenetic
      alterations. To determine the epigenomic alterations in ADPKD and their
      functional relevance, ADPKD and non-ADPKD individuals were analyzed by unbiased
      methylation profiling genome-wide and compared with their expression data.
      Intriguingly, PKD1 and other genes related to ion transport and cell adhesion
      were hypermethylated in gene-body regions, and their expressions were
      downregulated in ADPKD, implicating epigenetic silencing as the key mechanism
      underlying cystogenesis. Especially, in patients with ADPKD, PKD1 was
      hypermethylated in gene-body region and it was associated with recruitment of
      methyl-CpG-binding domain 2 proteins. Moreover, treatment with DNA methylation
      inhibitors retarded cyst formation of Madin-Darby Canine Kidney cells,
      accompanied with the upregulation of Pkd1 expression. These results are
      consistent with previous studies that knock-down of PKD1 was sufficient for
      cystogenesis. Therefore, our results reveal a critical role for hypermethylation
      of PKD1 and cystogenesis-related regulatory genes in cyst development, suggesting
      epigenetic therapy as a potential treatment for ADPKD. 

PMID- 24129833
TI  - Nanoscale structural and functional mapping of nacre by scanning probe microscopy
      techniques.
AB  - Nacre has received great attention due to its nanoscale hierarchical structure
      and extraordinary mechanical properties. Meanwhile, the nanoscale piezoelectric
      properties of nacre have also been investigated but the structure-function
      relationship has never been addressed. In this work, firstly we realized
      quantitative nanomechanical mapping of nacre of a green abalone using atomic
      force acoustic microscopy (AFAM). The modulus of the mineral tablets is
      determined to be ~80 GPa and that of the organic biopolymer no more than 23 GPa,
      and the organic-inorganic interface width is determined to be about 34 +/- 9 nm.
      Then, we conducted both AFAM and piezoresponse force microscopy (PFM) mapping in
      the same scanning area to explore the correlations between the nanomechanical and
      piezoelectric properties. The PFM testing shows that the organic biopolymer
      exhibits a significantly stronger piezoresponse than the mineral tablets, and
      they permeate each other, which is very difficult to reproduce in artificial
      materials. Finally, the phase hysteresis loops and amplitude butterfly loops were
      also observed using switching spectroscopy PFM, implying that nacre may also be a
      bio-ferroelectric material. The obtained nanoscale structural and functional
      properties of nacre could be very helpful in understanding its deformation
      mechanism and designing biomimetic materials of extraordinary properties.

PMID- 24129834
TI  - Dermal exposure to a compounded pain cream resulting in severely elevated
      clonidine concentration.
AB  - INTRODUCTION: Clonidine is an imidazoline derivative antihypertensive medication
      that is also used as adjunctive therapy for neuropathic pain disorders via
      topical administration. Clonidine overdose can manifest both central and
      peripheral alpha-adrenergic agonist effects. CASE REPORT: A 23-year-old man
      presented to an emergency department with altered mental status, bradycardia, and
      hypertension after suspected overdose. He had rubbed a specially compounded
      medicinal cream over his entire body containing clonidine 0.2 % (w/w), gabapentin
      6 %, imipramine 3 %, ketamine 10 %, lidocaine 2 %, and mefenamic acid 1 %. The
      patient presented with severe hypertension, bradycardia, and altered mental
      status. He was found to have a subarachnoid hemorrhage and was treated for
      hypertensive emergency. Toxicological analysis of initial blood samples revealed
      a serum clonidine concentration of 5,200 ng/ml. At 6-month follow-up, the patient
      had made a full recovery. DISCUSSION: There are limited reports of topical
      clonidine toxicity, and to our knowledge, this case involves the highest
      concentration yet reported following clonidine overdose by any route of exposure.
      The severely elevated serum clonidine concentration found in our patient
      demonstrates the possibility of toxicity resulting from inappropriate use of such
      a product. At high serum concentrations, the pharmacodynamic effects of clonidine
      appear to cause significant peripheral alpha-1 adrenergic stimulation.
      Toxicologists should be aware of the increasing use of topical clonidine
      preparations for the treatment of neuropathic pain and the potential for
      toxicity.

PMID- 24129835
TI  - A review of 29 incidents involving 4-aminopyridine in non-target species reported
      to the ASPCA Animal Poison Control Center.
AB  - 4-Aminopyridine (4-AP) is an avicide used in products that are approved by the
      Environmental Protection Agency (EPA) to control populations of various birds.
      Pharmaceutical 4-AP is also used in humans to treat neural and muscular
      dysfunctions associated with multiple sclerosis. Although strict restrictions for
      its use are in place, exposures to 4-AP bait by non-target species still occur.
      Twenty-nine exposures of 4-AP bait involving non-target species were identified
      and retrieved from the ASPCA Animal Poison Control Center medical record
      database. Canines were the most commonly exposed (86 %) species followed by
      felines (10 %). The highest frequency of exposures was reported from Colorado (22
      %). Most commonly reported clinical signs in canines were tremors,
      hypersalivation, seizures, tachycardia, and ataxia. The onset time of signs
      ranged from 5 to 300 min with an average of 89 min. Clinical signs lasted from 15
      to 84 h with an average of 37 h. Patient outcome was known in six cases; one dog
      died 4 h after the exposure and five made full recovery with supportive care.
      Treatment of five surviving patients included administration of activated
      charcoal, use of anticonvulsants and muscle relaxants like diazepam and
      methocarbamol, and intravenous fluids. Diagnosis of 4-AP toxicosis can be
      supported by testing the gastric contents of the exposed patient. Due to the
      rapid absorption, samples need to be collected and frozen/chilled promptly. For
      successful patient outcome, treatment must be implemented quickly after an
      exposure. 

PMID- 24129837
TI  - Pathogenic Providencia alcalifaciens strain that causes fatal hemorrhagic
      pneumonia in piglets.
AB  - Investigation of a serious pig disease with high mortality and typical lung
      lesions yielded a bacterial isolate identified as Providencia alcalifaciens based
      on the 16S ribosomal DNA sequence analysis. The pathogenicity of this bacterial
      isolate was confirmed in piglets and mice. The bacterial strain caused the
      typical illness in piglets, which suffered serious dyspnea and hemorrhagic
      pneumonia. The drug resistance spectrum of the bacterium was also determined. The
      results indicated that the isolate is resistant to 12 antibiotics and
      intermediately resistant to 10 antibiotics out of the 34 antibiotics tested. The
      current study is the first to report a serious lung disease in piglets caused by
      a multidrug resistant P. alcalifaciens isolate, which should be given more
      attention during surveillance and diagnostics.

PMID- 24129838
TI  - A new cytoplasmic monoheme cytochrome c from Acidithiobacillus ferrooxidans
      involved in sulfur oxidation.
AB  - Acidithiobacillus ferrooxidans can obtain energy from the oxidation of various
      reduced inorganic sulfur compounds (RISCs, e.g., sulfur) and ferrous iron in
      bioleaching so has multiple branched respiratory pathways with a diverse range of
      electron transporters, especially cytochrome c proteins. A cytochrome c family
      gene, afe1130, which has never been reported before, was found by screening the
      whole genome of A. ferrooxidans. Here we report the differential gene
      transcription, bioinformatics analysis, and molecular modeling of the protein
      encoded by the afe1130 gene (AFE1130). The differential transcription of the
      target afe1130 gene versus the reference rrs gene in the A. ferrooxidans,
      respectively, on the culture conditions of sulfur and ferrous energy sources was
      performed through quantitative reverse transcription polymerase chain reaction
      (qRT-PCR) with a SYBR green-based assay according to the standard curves method.
      The qRT-PCR results showed that the afe1130 gene in sulfur culture condition was
      obviously more transcribed than that in ferrous culture condition. Bioinformatics
      analysis indicated that the AFE1130 was affiliated to the subclass ID of class I
      of cytochrome c and located in cytoplasm. Molecular modeling results exhibited
      that the AFE1130 protein consisted of 5 alpha-helices harboring one heme c group
      covalently bonded by Cys13 and Cys16 and ligated by His17 and Met62 and owned a
      big raised hydrophobic surface responsible for attaching to inner cytomembrane.
      So the AFE1130 in A. ferrooxidans plays a role in the RISCs oxidation in
      bioleaching in cytoplasm bound to inner membrane. 

PMID- 24129839
TI  - Codon optimization enhances protein expression of Bombyx mori
      nucleopolyhedrovirus DNA polymerase in E. coli.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) is a major viral agent that causes
      deadly grasserie disease in silkworms, while BmNPV DNA polymerase (BmNPV-pol),
      encoded by ORF53 gene, plays a central role in viral DNA replication. Efficacy
      studies of BmNPV-POL are limited because of poor heterologous protein expression
      in E. coli. Here, we redesigned the BmNPV-pol to preferentially match codon
      frequencies of E. coli without altering the amino acid sequence. Following de
      novo synthesis, codon-optimized BmNPV-pol (co-BmNPV-pol) gene was cloned into
      pET32a and pGEX-4T-2 vector. The expression of co-BmNPV-POL in E. coli was
      significantly increased when BmNPV-POL was fused with GST protein rather than a
      His-tag. The co-BmNPV-POL fusion proteins were isolated using GST affinity
      chromatography and Mono Q iron exchange chromatography. Protein purity and
      identity were confirmed by western blot and MALDI-TOF analyses. The biological
      activity of purified proteins was measured on a poly(dA)/oligo(dT)
      primer/template. The specific polymerasing activity of the recombinant BmNPV-POL
      was 6,329 units/mg at optimal conditions. Thus, a large amount of purified
      protein as a soluble form with high activity would provide many benefits for the
      functional research and application of BmNPV-POL. 

PMID- 24129840
TI  - Animal Viruses Probe dataset (AVPDS) for microarray-based diagnosis and
      identification of viruses.
AB  - AVPDS (Animal Viruses Probe dataset) is a dataset of virus-specific and conserve
      oligonucleotides for identification and diagnosis of viruses infecting animals.
      The current dataset contain 20,619 virus specific probes for 833 viruses and
      their subtypes and 3,988 conserved probes for 146 viral genera. Dataset of virus
      specific probe has been divided into two fields namely virus name and probe
      sequence. Similarly conserved probes for virus genera table have genus, and
      subgroup within genus name and probe sequence. The subgroup within genus is
      artificially divided subgroups with no taxonomic significance and contains probes
      which identifies viruses in that specific subgroup of the genus. Using this
      dataset we have successfully diagnosed the first case of Newcastle disease virus
      in sheep and reported a mixed infection of Bovine viral diarrhea and Bovine
      herpesvirus in cattle. These dataset also contains probes which cross reacts
      across species experimentally though computationally they meet specifications.
      These probes have been marked. We hope that this dataset will be useful in
      microarray-based detection of viruses. The dataset can be accessed through the
      link https://dl.dropboxusercontent.com/u/94060831/avpds/HOME.html.

PMID- 24129841
TI  - Atypical antipsychotics for psychosis in adolescents.
AB  - BACKGROUND: Schizophrenia often presents in adolescence, but current treatment
      guidelines are based largely on studies of adults with psychosis. Over the past
      decade, the number of studies on treatment of adolescent-onset psychosis has
      increased. The current systematic review collates and critiques evidence obtained
      on the use of various atypical antipsychotic medications for adolescents with
      psychosis. OBJECTIVES: To investigate the effects of atypical antipsychotic
      medications in adolescents with psychosis. We reviewed in separate analyses
      various comparisons of atypical antipsychotic medications with placebo or a
      typical antipsychotic medication or another atypical antipsychotic medication or
      the same atypical antipsychotic medication but at a lower dose. SEARCH METHODS:
      We searched the Cochrane Schizophrenia Group Register (October 2011), which is
      based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and
      PsycINFO. We inspected references of all identified studies and contacted study
      authors and relevant pharmaceutical companies to ask for more information.
      SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs)
      that compared atypical antipsychotic medication with placebo or another
      pharmacological intervention or with psychosocial interventions, standard
      psychiatric treatment or no intervention in children and young people aged 13 to
      18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and
      transient psychoses or unspecified psychosis. We included studies published in
      English and in other languages that were available in standardised databases.
      DATA COLLECTION AND ANALYSIS: Review authors AK and SSD selected the studies,
      rated the quality of the studies and performed data extraction. For dichotomous
      data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a
      fixed-effect model. When possible, for binary data presented in the 'Summary of
      findings' table, we calculated illustrative comparative risks. We summated
      continuous data using the mean difference (MD). Risk of bias was assessed for
      included studies. MAIN RESULTS: We included 13 RCTs, with a total of 1112
      participants. We found no data on service utilisation, economic outcomes,
      behaviour or cognitive response. Trials were classified into the following
      groups. 1. Atypical antipsychotics versus placebo: Only two studies compared one
      atypical antipsychotic medication with placebo. In one study, the number of non
      responders treated with olanzapine was not different from the number treated with
      placebo (1 RCT, n = 107, RR 0.84, 95% CI 0.65 to 1.10); however, significantly
      more (57% vs 32%) people left the study early (1 RCT, n = 107, RR 0.56, 95% CI
      0.36 to 0.87) from the placebo group compared with the olanzapine group. With
      regard to adverse effects, young people treated with aripiprazole had
      significantly lower serum cholesterol compared with those given placebo (1 RCT, n
      = 302, RR 3.77, 95% CI 1.88 to 7.58). 2. Atypical antipsychotics versus typical
      antipsychotics: When the findings of all five trials comparing atypical
      antipsychotic medications with a typical antipsychotic medication were collated,
      no difference in the mean end point Brief Psychiatric Rating Scale (BPRS) score
      was noted between the two arms (5 RCTs, n = 236, MD -1.08, 95% CI -3.08 to 0.93).
      With regard to adverse effects, the mean end point serum prolactin concentration
      was much higher than the reference range for treatment with risperidone,
      olanzapine and molindone in one of the studies. However, fewer adolescents who
      were receiving atypical antipsychotic medications left the study because of
      adverse effects (3 RCTs, n = 187, RR 0.65, 95% CI 0.36 to 1.15) or for any reason
      (3 RCTs, n = 187, RR 0.62, 95% CI 0.39 to 0.97).3. One atypical antipsychotic
      versus another atypical antipsychotic: The mean end point BPRS score was not
      significantly different for people who received risperidone compared with those
      who received olanzapine; however, the above data were highly skewed. Overall no
      difference was noted in the number of people leaving the studies early because of
      any adverse effects between each study arm in the three studies comparing
      olanzapine and risperidone (3 RCTs, n = 130, RR 1.15, 95% CI 0.44 to 3.04).
      Specific adverse events were not reported uniformly across the six different
      studies included in this section of the review; therefore it was difficult to do
      a head-to-head comparison of adverse events for different atypical antipsychotic
      medications.4. Lower-dose atypical antipsychotic versus standard/higher-dose
      atypical antipsychotic: Three studies reported comparisons of lower doses of the
      atypical antipsychotic medication with standard/higher doses of the same
      medication. One study reported better symptom reduction with a standard dose of
      risperidone as compared with a low dose (1 RCT, n = 257, RR -8.00, 95% CI -13.75
      to -2.25). In another study, no difference was reported in the number of
      participants not achieving remission between the group receiving 10 mg/d and
      those who received 30 mg/d of aripiprazole (1 RCT, n = 196, RR 0.84, 95% CI 0.48
      to 1.48). Similarly in the other study, authors reported no statistically
      significant difference in clinical response between the two groups receiving
      lower-dose (80 mg/d) and higher-dose (160 mg/d) ziprasidone, as reflected by the
      mean end point BPRS score (1 RCT, n = 17, MD -4.40, 95% CI -19.20 to 10.40).
      AUTHORS' CONCLUSIONS: No convincing evidence suggests that atypical antipsychotic
      medications are superior to typical medications for the treatment of adolescents
      with psychosis. However, atypical antipsychotic medications may be more
      acceptable to young people because fewer symptomatic adverse effects are seen in
      the short term. Little evidence is available to support the superiority of one
      atypical antipsychotic medication over another, but side effect profiles are
      different for different medications. Treatment with olanzapine, risperidone and
      clozapine is often associated with weight gain. Aripiprazole is not associated
      with increased prolactin or with dyslipidaemia. Adolescents may respond better to
      standard-dose as opposed to lower-dose risperidone, but for aripiprazole and
      ziprasidone, lower doses may be equally effective. Future trials should ensure
      uniform ways of reporting.

PMID- 24129842
TI  - E-mental health self-management for psychotic disorders: state of the art and
      future perspectives.
AB  - OBJECTIVE: The aim of this review was to investigate to what extent information
      technology may support self-management among service users with psychotic
      disorders. The investigation aimed to answer the following questions: What types
      of e-mental health self-management interventions have been developed and
      evaluated? What is the current evidence on clinical outcome and cost
      effectiveness of the identified interventions? To what extent are e-mental health
      self-management interventions oriented toward the service user? METHODS: A
      systematic review of references through July 2012 derived from MEDLINE, PsycINFO,
      AMED, CINAHL, and the Library, Information Science and Technology database was
      performed. Studies of e-mental health self-management interventions for persons
      with psychotic disorders were selected independently by three reviewers. RESULTS:
      Twenty-eight studies met the inclusion criteria. E-mental health self-management
      interventions included psychoeducation, medication management, communication and
      shared decision making, management of daily functioning, lifestyle management,
      peer support, and real-time self-monitoring by daily measurements (experience
      sampling monitoring). Summary effect sizes were large for medication management
      (.92) and small for psychoeducation (.37) and communication and shared decision
      making (.21). For all other studies, individual effect sizes were calculated. The
      only economic analysis conducted reported more short-term costs for the e-mental
      health intervention. CONCLUSIONS: People with psychotic disorders were able and
      willing to use e-mental health services. Results suggest that e-mental health
      services are at least as effective as usual care or nontechnological approaches.
      Larger effects were found for medication management e-mental health services. No
      studies reported a negative effect. Results must be interpreted cautiously,
      because they are based on a small number of studies.

PMID- 24129844
TI  - Evidence of a syndemic among young Canadian gay and bisexual men: uncovering the
      associations between anti-gay experiences, psychosocial issues, and HIV risk.
AB  - Syndemic has become an important theoretical model toward understanding how
      psychosocial issues may interact to increase HIV acquisition among gay and
      bisexual men. We measured the extent to which anti-gay experiences are associated
      with psychosocial issues, which in turn were hypothesized to have an additive
      effect on HIV risk, in a sample of Canadian young gay and bisexual men. Sixty
      eight percent of men reported at least one form of anti-gay experience. For each
      additional form of anti-gay experience, our data demonstrated increased
      likelihood of psychosocial issues. Psychosocial issues had an additive effect,
      increasing the risk of unprotected intercourse in the last 12 months (doubling
      the risk for those with 3+ issues OR 1.95 [1.39-2.75]). Overall, our findings
      suggest that a syndemic is occurring among young Canadian gay and bisexual men,
      highlighting the need to expand HIV prevention efforts beyond sexual risk, to
      address stigma and gay men's broader health concerns.

PMID- 24129843
TI  - Investing in communities: evaluating the added value of community mobilization on
      HIV prevention outcomes among FSWs in India.
AB  - Community mobilization often requires greater time and resource investments than
      typical interventions, yet few evaluations exist to justify these investments. We
      evaluated the added benefit of community mobilization on HIV prevention outcomes
      among female sex workers (FSWs) using a composite measure of volunteer
      participation in program committees by FSWs. After adjusting for treatment
      propensity, we used multilevel structural equation modeling (MSEM) to test our
      program theory. We hypothesized that stronger community mobilization would be
      associated with increased levels of consistent condom use and with increased
      levels of perceived fairness, mediated by psychosocial processes. Community
      mobilization had an indirect effect on consistent condom use mediated through
      social cohesion and an indirect effect on perceived fairness mediated by
      collective efficacy. Our results suggest higher levels of community mobilization
      help improve condom use and reduce perceived discrimination beyond the effects of
      the core HIV intervention program. We recommend further testing of this model. 

PMID- 24129845
TI  - The gene cutA of Fusarium fujikuroi, encoding a protein of the haloacid
      dehalogenase family, is involved in osmotic stress and glycerol metabolism.
AB  - Survival of micro-organisms in natural habitats depends on their ability to adapt
      to variations in osmotic conditions. We previously described the gene cut-1 of
      Neurospora crassa, encoding a protein of the haloacid dehalogenase family with an
      unknown function in the osmotic stress response. Here we report on the functional
      analysis of cutA, the orthologous gene in the phytopathogenic fungus Fusarium
      fujikuroi. cutA mRNA levels increased transiently after exposure to 0.68 M NaCl
      and were reduced upon return to normal osmotic conditions; deletion of the gene
      resulted in a partial reduction in tolerance to osmotic stress. DeltacutA mutants
      contained much lower intracellular levels of glycerol than the wild-type, and did
      not exhibit the increase following hyper-osmotic shock expected from the high
      osmolarity glycerol (HOG) response. cutA is linked and divergently transcribed
      with the putative glycerol dehydrogenase gene gldB, which showed the same
      regulation by osmotic shock. The intergenic cutA/gldB regulatory region contains
      putative stress-response elements conserved in other fungi, and both genes shared
      other regulatory features, such as induction by heat shock and by illumination.
      Photoinduction was also observed in the HOG response gene hogA, and was lost in
      mutants of the white collar gene wcoA. Previous data on glycerol production in
      Aspergillus spp. and features of the predicted CutA protein lead us to propose
      that F. fujikuroi produces glycerol from dihydroxyacetone, and that CutA is the
      enzyme involved in the synthesis of this precursor by dephosphorylation of
      dihydroxyacetone-3P. 

PMID- 24129846
TI  - A tomato endoplasmic reticulum (ER)-type omega-3 fatty acid desaturase (LeFAD3)
      functions in early seedling tolerance to salinity stress.
AB  - KEY MESSAGE: Transgenic tomato plants overexpressing LeFAD3 sense and antisense
      sequences were generated. Salt stress suppressed the growth of WT and antisense
      plants to a higher extent than that in sense plants. In this study, we
      investigated the role of the LeFAD3-encoding ER-type omega-3 fatty acid
      desaturase in salt tolerance in tomato plants. We created transgenic tomato
      plants by overexpressing its sense and antisense sequences under the control of
      the cauliflower mosaic virus 35S promoter. Based on the results of northern and
      western blotting as well as quantitative reverse transcription-polymerase chain
      reaction, sense plants expressed more desaturase than wild-type (WT) plants,
      whereas antisense plants expressed less desaturase than WT. Salt stress
      suppressed the growth of both WT and antisense plants to a higher extent than
      that in sense plants, which can be attributed to the fact that sense plants
      performed better in maintaining the integrity of the membrane system, as revealed
      by electron microscopy. The concomitant increase in superoxide dismutase (EC
      1.15.1.1) and ascorbate peroxidase (EC 1.11.1.7) may have alleviated the
      photoinhibition caused by the increased level of ROS in sense plants. Our results
      suggest that LeFAD3 overexpression can enhance the tolerance of early seedlings
      to salinity stress.

PMID- 24129847
TI  - High throughput Agrobacterium tumefaciens-mediated germline transformation of
      mechanically isolated meristem explants of cotton (Gossypium hirsutum L.).
AB  - KEY MESSAGE: Agrobacterium tumefaciens mediates high frequency of germline
      transformation of cotton meristem explants. The meristem transformation system we
      developed is rapid, high throughput and genotype-flexible. We have developed a
      high throughput cotton transformation system based on direct Agrobacterium
      inoculation of mechanically isolated meristem explants of cotton (Gossypium
      hirsutum L.). The explants were inoculated with a disarmed A. tumefaciens strain,
      AB33 harboring a 2 T-DNA binary vector pMON114908. This vector contained a gene
      of interest, an intron-disrupted beta-glucuronidase gene in one T-DNA, and a
      selectable marker gene, aadA in the other T-DNA. Critical factors, such as method
      of co-culture, culture temperature during selection, composition of selection
      medium, and selection scheme were found to influence transformation frequency.
      The cycle time from initial inoculation to the transplanting of transgenic plants
      to soil was 7-8 weeks. Stable integration of transgenes and their transmission to
      progeny were confirmed by molecular and genetic analyses. Transgenes segregated
      in the expected Mendelian fashion in the T1 generation for most of the transgenic
      events. It was possible to recover marker-free events in the T1 generation when
      utilizing a binary vector that contained the selectable marker and gene of
      interest expression cassettes on independent T-DNAs. The procedure presented here
      has been used to regenerate thousands of independent transgenic events from
      multiple varieties with numerous constructs, and we believe it represents a major
      step forward in cotton transformation technology.

PMID- 24129849
TI  - Ethnic and gender variations in the associations between family cohesion, family
      conflict, and depression in older Asian and Latino adults.
AB  - To examine the associations between family conflict, family cohesion and late
      life depression in Latino and Asian populations and test if these associations
      vary by race/ethnicity and gender. We used a subsample of older adults from the
      National Latino Asian American Study (N = 395). All analyses were weighted and
      adjusted for individual and clinical characteristics. Greater family cohesion was
      associated with decrease in risk for depression in Latino and Asian older adult
      populations (OR: 0.68, 95% CI: 0.54, 0.84). These associations varied by gender,
      with men being more sensitive to family cohesion and family conflict than women.
      Asian older adults were more sensitive to family conflict, whereas Latino older
      adults were more sensitive to family cohesion. The quality of family
      relationships is strongly associated with late-life depression. Further research
      is needed to better understand the complex interplay between social support,
      ethnicity, and gender in latelife depression outcomes.

PMID- 24129850
TI  - The interplay of AMP-activated protein kinase and androgen receptor in prostate
      cancer cells.
AB  - AMP-activated protein kinase (AMPK) has recently emerged as a potential target
      for cancer therapy due to the observation that activation of AMPK inhibits tumor
      cell growth. It is well-known that androgen receptor (AR) signaling is a major
      driver for the development and progression of prostate cancer and that
      downregulation of AR is a critical step in the induction of apoptosis in prostate
      cancer cells. However, little is known about the potential interaction between
      AMPK and AR signaling pathways. In the current study, we showed that activation
      of AMPK by metformin caused decrease of AR protein level through suppression of
      AR mRNA expression and promotion of AR protein degradation, demonstrating that
      AMPK activation is upstream of AR downregulation. We also showed that inhibition
      of AR function by an anti-androgen or its siRNA enhanced AMPK activation and
      growth inhibition whereas overexpression of AR delayed AMPK activation and
      increased prostate cancer cellular resistance to metformin treatment, suggesting
      that AR suppresses AMPK signaling-mediated growth inhibition in a feedback
      mechanism. Our findings thus reveal a novel AMPK-AR regulatory loop in prostate
      cancer cells and should have a potential clinical significance.

PMID- 24129851
TI  - Urinary tract pacemaker cells: current knowledge and insights from nonrenal
      pacemaker cells provide a basis for future discovery.
AB  - Coordinated ureteric peristalsis propels urine from the kidney to the bladder.
      Cells in the renal pelvis and ureter spontaneously generate and propagate
      electrical activity to control this process. Recently, c-kit tyrosine kinase and
      hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) were
      identified in the upper urinary tract. Both of these proteins are required for
      coordinated proximal to distal contractions in the ureter. Alterations in
      pacemaker cell expression are present in multiple congenital kidney diseases,
      suggesting a functional contribution by these cells to pathologic states. In
      contrast to gut and heart pacemaker cells, the developmental biology of ureteric
      pacemaker cells, including cell lineage and signaling mechanisms, is undefined.
      Here, we review pacemaker cell identify and function in the urinary pelvis and
      ureter and the control of pacemaker function by Hedgehog-GLI signaling. Next, we
      highlight current knowledge of gut and heart pacemaker cells that is likely to
      provide insight into developmental mechanisms that could control urinary
      pacemaker cells. 

PMID- 24129852
TI  - [Challenges of Clostridium difficile infection].
AB  - Clostridium difficile infections remain a problem especially for patients in the
      intensive care unit. The fact that C. difficile infections are strongly
      associated with antibiotic therapy calls for more caution in the use of
      antibiotics, especially in patients with a high risk of developing C. difficle
      infections. Severe infections and recurrent episodes are usually difficult to
      manage and therapeutic options are often limited. The method of stool
      transplantation, though not new, has received more attention in recent years,
      with studies showing stool transplantation to be a promising and easy method
      which has high clinical cure rates even for recurrent C. difficile infections.
      However, more randomised and controlled trials are needed to further study the
      efficacy of stool transplantation in patients with C. difficile infection. 

PMID- 24129853
TI  - Anticonvulsants for fibromyalgia.
AB  - BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of
      unknown aetiology characterised by chronic widespread pain that often co-exists
      with sleep problems and fatigue. People often report high disability levels and
      poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key
      symptoms and disability, and improving HRQoL. Anticonvulsants (antiepileptic
      drugs) are drugs frequently used for the treatment of chronic pain syndromes.
      OBJECTIVES: To assess the benefits and harms of anticonvulsants for treating FM
      symptoms. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (Issue 8, 2013), MEDLINE (1966 to August 2013), PsycINFO (1966
      to August 2013), SCOPUS (1980 to August 2013) and the reference lists of reviewed
      articles for published studies and www.clinicaltrials.gov (to August 2013) for
      unpublished trials. SELECTION CRITERIA: We selected randomised controlled trials
      of any formulation of anticonvulsants used for the treatment of people with FM of
      any age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      the data of all included studies and assessed the risks of bias of the studies.
      We resolved discrepancies by discussion. MAIN RESULTS: We included eight studies:
      five with pregabalin and one study each with gabapentin, lacosamide and
      levetiracetam. A total of 2480 people were included into anticonvulsants groups
      and 1099 people in placebo groups. The median therapy phase of the studies was 13
      weeks. The amount and quality of evidence were insufficient to draw definite
      conclusions on the efficacy and safety of gabapentin, lacosamide and
      levetiracetam in FM. The amount and quality of evidence was sufficient to draw
      definite conclusions on the efficacy and safety of pregabalin in FM. Therefore,
      we focused on our interpretation of the evidence for pregabalin due to our
      greater certainty about its effects and its greater relevance to clinical
      practice. All pregabalin studies had a low risk of bias. Reporting a 50% or
      greater reduction in pain was more frequent with pregabalin use than with a
      placebo (risk ratio (RR) 1.59; 95% confidence interval (CI) 1.33 to 1.90; number
      needed to treat for an additional beneficial outcome (NNTB) 12; 95% CI 9 to 21).
      The number of people who reported being 'much' or 'very much' improved was higher
      with pregabalin than with placebo (RR 1.38; 95% CI 1.23 to 1.55; NNTB 9; 95% CI 7
      to 15). Pregabalin did not substantially reduce fatigue (SMD -0.17; 95% CI -0.25
      to -0.09; 2.7% absolute improvement on a 1 to 50 scale) compared with placebo.
      Pregabalin had a small benefit over placebo in reducing sleep problems by 6.2%
      fewer points on a scale of 0 to 100 (standardised mean difference (SMD) -0.35;
      95% CI -0.43 to -0.27). The dropout rate due to adverse events was higher with
      pregabalin use than with placebo use (RR 1.68; 95% CI 1.36 to 2.07; number needed
      to treat for an additional harmful outcome (NNTH) 13; 95% CI 9 to 23). There was
      no significant difference in serious adverse events between pregabalin and
      placebo use (RR 1.03; 95% CI 0.71 to 1.49). Dizziness was reported as an adverse
      event more frequently with pregabalin use than with placebo use (RR 3.77; 95% CI
      3.06 to 4.63; NNTH 4; 95% CI 3 to 5). AUTHORS' CONCLUSIONS: The anticonvulsant,
      pregabalin, demonstrated a small benefit over placebo in reducing pain and sleep
      problems. Pregabalin use was shown not to substantially reduce fatigue compared
      with placebo. Study dropout rates due to adverse events were higher with
      pregabalin use compared with placebo. Dizziness was a particularly frequent
      adverse event seen with pregabalin use. At the time of writing this review,
      pregabalin is the only anticonvulsant drug approved for treating FM in the US and
      in 25 other non-European countries. However, pregabalin has not been approved for
      treating FM in Europe. The amount and quality of evidence were insufficient to
      draw definite conclusions on the efficacy and safety of gabapentin, lacosamide
      and levetiracetam in FM.

PMID- 24129855
TI  - Nano-solenoid: helicoid carbon-boron nitride hetero-nanotube.
AB  - As a fundamental element of a nanoscale passive circuit, a nano-inductor is
      proposed based on a hetero-nanotube consisting of a spiral carbon strip and a
      spiral boron nitride strip. It is shown by density functional theory associated
      with nonequilibrium Green function calculations that the nanotube exhibits
      attractive transport properties tunable by tube chirality, diameter, component
      proportion and connection manner between the two strips, with excellent 'OFF'
      state performance and high current on the order of 10-100 MUA. All the hetero
      nanotubes show negative differential resistance. The transmission peaks of
      current are absolutely derived from the helicoid carbon strips or C-BN
      boundaries, giving rise to a spiral current analogous with an energized nano
      solenoid. According to Ampere's Law, the energized nano-solenoid can generate a
      uniform and tremendous magnetic field of more than 1 tesla, closing to that
      generated by the main magnet of medical nuclear magnetic resonance. Moreover, the
      magnitude of magnetic field can be easily modulated by bias voltage, providing
      great promise for a nano-inductor to realize electromagnetic conversion at the
      nanoscale. 

PMID- 24129854
TI  - Laparoscopic splenectomy in patients with hereditary spherocytosis: report on 12
      consecutive cases.
AB  - Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency
      in erythrocyte membrane proteins. Removal of the spleen may reduce the intra
      splenic hemolytic process of the disease and, therefore, may correct the anemia.
      Furthermore, it seems to decrease the levels of serum bilirubin, thus reducing
      the formation of gallbladder stones. Indications and timing of splenectomy,
      however, are still debated. Twelve patients with severe hereditary spherocytosis
      operated on with laparoscopic splenectomy were retrospectively reviewed. Median
      age at diagnosis was 13.8 years (range 8-25 years). Male to female ratio was 5/7.
      Indications for laparoscopic removal of the spleen included anemia unresponsive
      to iron supplementation in eight patients (66.6 %) with increase need for red
      cells transfusions, and jaundice with symptoms related to cholelitiasis in four
      patients (33.3 %). Laparoscopic splenectomy was associated in four cases to
      laparoscopic cholecystectomy. Mean operative time was 50 min (range 40-75 min)
      with no conversion to open surgery. Mean hospital stay ranged from 3 to 7 days.
      In a 16-month follow-up, no complications were recorded and a persistent
      correction of anemia was observed. With the advent of laparoscopic surgery,
      splenectomy has been performed by this mini-invasive approach in referral
      centers. Laparoscopic splenectomy is an effective technique, when performed in
      patients with hereditary spherocytosis. Low complication rate and persistent
      correction of the hematologic disorders can be expected after the laparoscopic
      splenectomy, provided that a proper technique is performed and an experienced
      surgical team is available.

PMID- 24129856
TI  - Use of a once-daily NSAID in treatment of cyclic vomiting syndrome.
AB  - Cyclic vomiting syndrome (CVS) is a rare disorder characterized by episodes of
      intense vomiting and nausea separated by symptom-free periods. We report the case
      of a 71-year-old man who presented with a long history of poorly controlled CVS
      whose symptoms resolved with the addition of a once-daily dose of meloxicam, a
      semi-selective non-steroidal anti-inflammatory drug (NSAID). This is the first
      report of symptom alleviation in a CVS patient using a once-daily NSAID, as well
      as one with selectivity to COX-2 inhibition. This is important due to both the
      increased compliance seen with once-daily medications, as well as the decreased
      gastrointestinal effects seen with selective COX-2 inhibitors compared to
      nonselective NSAIDS. 

PMID- 24129857
TI  - Nontraditional risk factors as mediators of racial differences in diabetes risk.

PMID- 24129858
TI  - EHRs in a web 2.0 world: time to embrace a problem-list Wiki.

PMID- 24129859
TI  - Evaluating the brief health literacy screen--the authors' reply.

PMID- 24129860
TI  - Evaluating the brief health literacy screen.

PMID- 24129861
TI  - Capsule commentary on Oslin et al., a randomized clinical trial of alcohol care
      management delivered in Department of Veterans Affairs primary care clinics
      versus specialty addiction treatment.

PMID- 24129862
TI  - Peer review: the year in review.

PMID- 24129863
TI  - Empirical prediction of electronic potentials of single-walled carbon nanotubes
      with a specific chirality (n,m).
AB  - The determination of the electronic states of single-walled carbon nanotubes
      (SWNTs) with a specific chirality has been a central issue in the science of
      SWNTs. Here we present the empirical equations with fitting parameters for the
      determination of the reduction and oxidation potentials of SWNTs for a wide range
      of diameters and chiral angles. In these equations, a distinct chirality family
      dependence of the reduction potentials is observed, while the oxidation
      potentials show a simple diameter dependence nearly proportional to the inversed
      nanotube diameter. Based on observations of the asymmetric chirality dependence
      between the reduction and oxidation potentials, the Fermi levels of the SWNTs
      were revealed to have a definite chirality family dependence, which indicates
      that the work functions of the SWNTs with small diameters deviate from the values
      for the large diameter SWNTs and graphene. We also performed quantum chemical
      calculations to compare the experiment to the calculations. 

PMID- 24129864
TI  - "Life is not a dress rehearsal:" it's time to take care of ourselves and our
      learners.

PMID- 24129865
TI  - Remembering Ian McWhinney.
AB  - Ian McWhinney, MD, who passed away 1 year ago this month, was a founder of family
      medicine in North America. As a social philosopher and a naturalist, he had a
      great influence on the development of family medicine. 

PMID- 24129866
TI  - Resident wellness behaviors: relationship to stress, depression, and burnout.
AB  - BACKGROUND AND OBJECTIVES: Stress in medical education has been well documented,
      often with the primary focus on negative factors such as depression and burnout.
      Few studies have attempted to assess well-being mediating behaviors. This study
      describes the relationship between wellness behaviors and measures of well-being
      at the start of family medicine residency. METHODS: Using an online
      questionnaire, first-year family medicine residents (n=168) completed
      standardized measures exploring perceived stress, depression, satisfaction with
      life, and burnout. A lifestyle wellness behavior measure was developed for the
      study. RESULTS: Average reported perceived stress levels were consistent with
      ranges found for medical students and residents. Twenty-three percent of
      residents scored in a range consistent with depression risk. In terms of burnout
      risk, 13.7% scored in the high emotional exhaustion range and 23.8% in the high
      depersonalization range. Two thirds reported high life satisfaction. Higher
      depersonalization and less time in nurturing relationships were associated with
      greater likelihood of medication use for sleep, mood, and anxiety in females.
      Higher alcohol use was associated with increased levels of perceived stress,
      burnout, and depression. The two wellness behaviors most associated with higher
      well-being were restful sleep and exercise. CONCLUSIONS: At the start of
      residency, well-being measures are consistent with findings in medical school.
      Restful sleep and exercise were associated with more positive well-being. Future
      longitudinal data analysis will help clarify the effect of residency training in
      well-being and lifestyle behaviors. Identification of protective factors and
      coping mechanisms could guide residencies in incorporating support services for
      residents.

PMID- 24129867
TI  - Direct patient interventions that can reduce maternal mortality in developing
      countries: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Maternal mortality is a major concern in developing
      countries. This study identified and evaluated specific direct patient
      interventions made in developing countries that could result in a decrease of the
      maternal mortality rate. METHODS: A systematic review of articles from Cochrane
      Library and MEDLINE databases was conducted. Articles chosen for review focused
      on small, practical, clinical interventions, while large, program, or government
      policy-based interventions were excluded. RESULTS: Sixty-eight articles were
      reviewed, and nine were selected for evaluation. Calcium supplementation during
      pregnancy had a maternal mortality relative risk of 0.80 (95% CI=0.70--0.91).
      Women with an interpregnancy interval of 18 to 24 months have a significantly
      lower risk of complications, while shorter and longer interpregnancy intervals
      were associated with an increase in maternal adverse outcomes or maternal death
      (adjusted odds ratio 2.54; 95% CI 1.22-5.38). Active management of the third
      stage of labor, specifically the use of uterotonic agents, decreased a woman's
      risk of postpartum hemorrhage, which is the leading cause of maternal mortality
      in most developing countries. CONCLUSIONS: The use of calcium supplementation to
      decrease maternal mortality is beneficial with a Grade A Recommendation.
      Educating women to space pregnancies according to lowest risk times is given a
      Grade D Recommendation. Using uterotonics as active management of the third stage
      of labor is given a Grade B Recommendation. These simple implementations can
      potentially save many lives, especially in remote areas and areas of low
      resource.

PMID- 24129868
TI  - Effect of a web-based curriculum on primary care practice: basic skin cancer
      triage trial.
AB  - BACKGROUND AND OBJECTIVES: Primary care physicians (PCPs) are uniquely positioned
      to detect melanoma. Effective educational interventions targeted at PCPs may
      improve early melanoma detection. A previous in-person Basic Skin Cancer Triage
      (BSCT) 2-hour course demonstrated significant short-term improvement in provider
      practices, attitudes, ability, confidence, and knowledge. We conducted a
      randomized trial to test the efficacy of the BSCT course implemented as a web
      based learning program, compared to a similar (control) web-based course on
      weight assessment. METHODS: We recruited a sample of 57 PCPs and 3,341 of their
      patients from four geographically diverse centers. Skin cancer control activities
      by PCPs were assessed by physician survey and by chart review and patient
      telephone interview about their recent visit to their PCP at baseline and at 1--2
      months and 12 months after course completion. RESULTS: Some effect of
      intervention on skin cancer parameters was self-reported by physicians; this was
      not confirmed by patient survey or chart-extracted data. Rates of skin cancer
      control practices by PCPs were low across both groups before and after
      intervention. The positive changes in physician-reported behaviors (total body
      skin examination [TBSE]), intentions (discuss skin cancer detection), confidence
      (performing TBSE), office practices, and knowledge (58% skin versus 49% control)
      were neither matched by differences in practice reported by their patients, nor
      persisted in a longer term follow-up, hence may be attributable to physician
      recall bias due to the experience of the course or desire to please study
      investigators and were less dramatic as compared to our previously reported in
      person BSCT intervention. Thus this approach by itself appears unlikely to result
      in improved PCP handling of skin cancer issues. CONCLUSIONS: Given previous
      success with our in-person course, the features required to make WBL a more
      effective tool for medical education must be further explored.

PMID- 24129869
TI  - Students' perceptions of the impact a creative arts journal has on their medical
      education.
AB  - BACKGROUND AND OBJECTIVES: Student-produced creative arts journals now exist in
      several medical schools. The Florida State University College of Medicine
      (FSUCOM) has created HEAL: Humanism Evolving through Arts and Literature. This
      study sought to determine what influence, if any, HEAL publications may have on
      medical students. METHODS: A survey utilizing Likert scale questions was sent to
      Florida State University medical students. Student responses were tabulated and
      analyzed using SAS 9.2 and MS Excel. A total of 241 (49.5%) students responded to
      the survey. RESULTS: About 81% of the respondents enjoyed reading HEAL. Many
      respondents agreed that HEAL promoted patient-centered care (55.9%) and could
      prevent burnout (61.8%). Sixty-four percent thought that HEAL helped them to
      understand their colleagues and classmates. CONCLUSIONS: This survey found that
      the medical students perceive HEAL as having positive value.

PMID- 24129870
TI  - Teaching by example: educating medical students through a weight management
      experience.
AB  - BACKGROUND AND OBJECTIVES: Surgeons General, the Institute of Medicine, and
      others have called for physicians to be role models for meeting the obesity
      epidemic. There are few published reports describing undergraduate medical
      education obesity curriculum elements. Physician experiences, knowledge, and
      attitudes have been shown to affect patient counseling behavior of physicians.
      METHODS: Required and extra credit obesity educational interventions were
      designed for third-year family medicine clerkship. For extra credit, students
      completed a personal weight management experience that spanned at least 4 weeks,
      included calculations of body mass index (BMI), waist circumference, caloric
      needs, description of eating and physical activity and monitoring plan, and a
      final report and reflection. RESULTS: During 2011--2012, 72% of the students
      completed this extra credit activity with almost all losing or maintaining their
      weight. Most reflected gratitude for this opportunity and their increased empathy
      for patients as they struggle with weight issues. CONCLUSIONS: Medical students
      completing a weight management experience during their third-year clerkship can
      see the effects on their own health while developing empathy for and
      understanding of the weight management struggles of their patients. Minimal
      faculty time commitment is required.

PMID- 24129871
TI  - Nursing home practice among recent family medicine residency graduates.
AB  - BACKGROUND AND OBJECTIVES: As the US population ages, nursing homes need more
      care providers. However, family physicians are narrowing their scope of practice.
      Characterizing family medicine practice patterns is essential for educational and
      workforce planning related to nursing home practice. METHODS: We analyzed a
      survey of 1,506 family medicine residency graduates from the Pacific Northwest
      between 1997 and 2009, examining whether they practiced in nursing homes and felt
      prepared for this practice. RESULTS: Nursing home practice among recent family
      medicine residency graduates declined from 61.4% in 1997 to 25.9% in 2009,
      despite no change in perceived level of preparedness for this practice.
      CONCLUSIONS: The Pacific Northwest has experienced a significant decline in
      nursing home practice among recent family medicine residency graduates. Further
      research is needed to elucidate the reasons for this workforce change and to plan
      for the increased need in nursing home providers.

PMID- 24129872
TI  - Meaningful scut work.

PMID- 24129873
TI  - Not a giggle: my experience with hand-foot-and-mouth disease as an adult.

PMID- 24129874
TI  - Patient with gun.

PMID- 24129877
TI  - Defining scholarship.

PMID- 24129878
TI  - Towards a self-assembled honeycomb structure via diaminotriptycene metal
      complexes.
AB  - We illustrate a new approach toward the synthesis of a porous supramolecular
      honeycomb based on triptycene. A coordination polymer has been prepared where the
      triptycene groups are linked through triptycenesemiquinonediimine platinum
      complexes, but the product is disordered rather than the intended honeycomb
      structure. A model platinum complex and its (15)N-labeled isotopomer have been
      prepared and characterized. 

PMID- 24129879
TI  - Pontibacter soli sp. nov., isolated from the soil of a Populus rhizosphere in
      Xinjiang, China.
AB  - A Gram-stain negative, rod-shaped, non-motile and pink-pigmented bacterial
      strain, designated strain HYL7-26(T), was isolated from a soil in the Desert Park
      of Huyang forest located in Xinjiang, China. Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that strain HYL7-26(T) belongs to the genus
      Pontibacter in the family Cytophagaceae. The 16S rRNA gene sequence similarity
      between strain HYL7-26(T) and type strains of Pontibacter species ranged from
      93.2 to 96.0 %. Strain HYL7-26(T) was found to contain iso-C15:0 (15.9 %), iso
      C17:0 3-OH (9.5 %) and summed feature 4 (comprising anteiso-C17:1 B and/or iso
      C17:1 I, 21.0 %, as defined by the MIDI system) as the major cellular fatty
      acids. The major respiratory quinone was identified as MK-7 and the DNA G+C
      content was determined to be 43.8 mol%. sym-Homospermidine was the major
      polyamine observed in the cells. On the basis of phenotypic, chemotaxonomic and
      phylogenetic data, strain HYL7-26(T) is considered to represent a novel species
      of the genus Pontibacter, for which the name Pontibacter soli sp. nov. is
      proposed. The type strain is HYL7-26(T) (=CCTCC AB 206240(T) = NRRL B-59490(T)). 

PMID- 24129880
TI  - Level-of-care criteria for peer support services: a best-practice guide.
AB  - Peer support services (PSS) are an expanding part of the continuum of care
      provided for behavioral health conditions. These services have been deemed an
      evidence-based reimbursable model of care by the Centers for Medicare and
      Medicaid Services. States, counties, employers, and health plans are increasingly
      covering PSS in benefit plans. Controlled and experimental studies are building
      the evidence base for these services. Medicaid and the states have not developed
      level-of-care or medical necessity criteria for PSS, even though these criteria
      are standards for determining coverage and reimbursement. This review of emerging
      level-of-care criteria for PSS provides a framework for the further development
      of these resources. 

PMID- 24129881
TI  - Recent progress in the development of bimetallic photocatalysts for hydrogen
      generation.
AB  - In this contribution recent developments in the design and application of
      bimetallic photocatalysts for the generation of hydrogen via intramolecular
      processes are assessed. The basic concepts of such assemblies are discussed
      together with an overview of the factors and molecular issues that affect their
      potential as photocatalysts. Issues that so far have limited progress are
      discussed and suggestions for future directions are made. 

PMID- 24129882
TI  - Incorporating the excluded solvent volume and surface charges for computing
      solvation free energy.
AB  - Gauss's law or Poisson's equation is conventionally used to calculate solvation
      free energy. However, the near-solute dielectric polarization from Gauss's law or
      Poisson's equation differs from that obtained from molecular dynamics (MD)
      simulations. To mimic the near-solute dielectric polarization from MD
      simulations, the first-shell water was treated as two layers of surface charges,
      the densities of which are proportional to the electric field at the solvent
      molecule that is modeled as a hard sphere. The intermediate water was treated as
      a bulk solvent. An equation describing the solvation free energy of ions using
      this solvent scheme was derived using the TIP3P water model.

PMID- 24129883
TI  - Social status attainment during the transition to adulthood.
AB  - The transition from adolescence to adulthood is a critical time for status
      attainment, with income, education, work experience, and independence from
      parents accruing at varying speeds and intensities. This study takes an
      intergenerational life-course perspective that incorporates parents' and one's
      own social status to examine the status attainment process from adolescence into
      adulthood in the domains of economic capital (e.g., income) and human capital
      (e.g., education, occupation). Survey data from three waves of the National
      Longitudinal Study of Adolescent Health (analytic n = 8,977) are analyzed using
      latent class analysis to capture the ebb and flow of social status advantages and
      disadvantages from adolescence (Wave 1) through young adulthood (Wave 3) into
      adulthood (Wave 4). The analytic sample is composed of 50.3 % females and 70.2 %
      Whites, 15.3 % Blacks, 11.0 % Hispanics, and 3.5 % Asians ages 12-18 at Wave 1
      and 25-31 at Wave 4. Four latent classes are found for economic capital and five
      for human capital. The importance of parents' social status is demonstrated by
      the presence of large groups with persistently low and persistently high social
      status over time in both domains. The capacity of individuals to determine their
      own status, however, is shown by equally large groups with upward and downward
      mobility in both domains. These findings demonstrate the dynamic nature of social
      status during this critical developmental period. 

PMID- 24129884
TI  - Inequality matters: classroom status hierarchy and adolescents' bullying.
AB  - The natural emergence of status hierarchies in adolescent peer groups has long
      been assumed to help prevent future intragroup aggression. However, clear
      evidence of this beneficial influence is lacking. In fact, few studies have
      examined between-group differences in the degree of status hierarchy (defined as
      within-group variation in individual status) and how they are related to
      bullying, a widespread form of aggression in schools. Data from 11,296 eighth-
      and ninth-graders (mean age = 14.57, 50.6 % female) from 583 classes in 71
      schools were used to determine the direction of the association between classroom
      degree of status hierarchy and bullying behaviors, and to investigate prospective
      relationships between these two variables over a 6-month period. Multilevel
      structural equation modeling analyses showed that higher levels of classroom
      status hierarchy were concurrently associated with higher levels of bullying at
      the end of the school year. Higher hierarchy in the middle of the school year
      predicted higher bullying later in the year. No evidence was found to indicate
      that initial bullying predicted future hierarchy. These findings highlight the
      importance of a shared balance of power in the classroom for the prevention of
      bullying among adolescents. 

PMID- 24129885
TI  - Identification of differentially expressed microRNAs in human hepatocellular
      adenoma associated with type I glycogen storage disease: a potential utility as
      biomarkers.
AB  - BACKGROUND: It is known that malignant transformation to hepatocellular carcinoma
      (HCC) occurs at a higher frequency in hepatocellular adenoma (HCA) from type I
      glycogen storage disease (GSD I) compared to HCA from other etiologies. In this
      study, we aimed to identify differentially expressed miRNAs in GSD Ia HCA as
      candidates that could serve as putative biomarkers for detection of GSD Ia HCA
      and/or risk assessment of malignant transformation. METHODS: Utilizing massively
      parallel sequencing, the miRNA profiling was performed for paired adenomas and
      normal liver tissues from seven GSD Ia patients. Differentially expressed miRNAs
      were validated in liver tumor tissues, HCC cell lines and serum using
      quantitative RT-PCR. RESULTS: miR-34a, miR-34a, miR-224, miR-224, miR-424, miR
      452 and miR-455-5p were found to be commonly deregulated in GSD Ia HCA, general
      population HCA, and HCC cell lines at compatible levels. In comparison with GSD
      Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b
      5p, and miR-214 were more significant in HCC cell lines. Furthermore, serum level
      of miR-130b in GSD Ia patients with HCA was moderately higher than that in either
      GSD Ia patients without HCA or healthy individuals. CONCLUSION: We make the first
      observation of distinct miRNA deregulation in HCA associated with GSD Ia. We also
      provide evidence that miR-130b could serve as a circulating biomarker for
      detection of GSD Ia HCA. This work provides prominent candidate miRNAs worth
      evaluating as biomarkers for monitoring the development and progress of liver
      tumors in GSD Ia patients in the future.

PMID- 24129886
TI  - Behavioural therapies versus other psychological therapies for depression.
AB  - BACKGROUND: Behavioural therapies represent one of several categories of
      psychological therapies that are currently used in the treatment of depression.
      However, the effectiveness and acceptability of behavioural therapies for
      depression compared with other psychological therapies remain unclear.
      OBJECTIVES: 1. To examine the effects of all BT approaches compared with all
      other psychological therapy approaches for acute depression.2. To examine the
      effects of different BT approaches (behavioural therapy, behavioural activation,
      social skills training and relaxation training) compared with all other
      psychological therapy approaches for acute depression.3. To examine the effects
      of all BT approaches compared with different psychological therapy approaches
      (CBT, third wave CBT, psychodynamic, humanistic and integrative psychological
      therapies) for acute depression. SEARCH METHODS: We searched the Cochrane
      Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR,
      31/07/2013), which includes relevant randomised controlled trials from The
      Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967
      ). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists
      of the included studies and relevant reviews for additional published and
      unpublished studies. SELECTION CRITERIA: Randomised controlled trials that
      compared behavioural therapies with other psychological therapies for acute
      depression in adults. DATA COLLECTION AND ANALYSIS: Two or more review authors
      independently identified studies, assessed trial quality and extracted data. We
      contacted study authors for additional information. MAIN RESULTS: Twenty-five
      trials involving 955 participants compared behavioural therapies with one or more
      of five other major categories of psychological therapies (cognitive-behavioural,
      third wave cognitive-behavioural, psychodynamic, humanistic and integrative
      therapies). Most studies had a small sample size and were assessed as being at
      unclear or high risk of bias. Compared with all other psychological therapies
      together, behavioural therapies showed no significant difference in response rate
      (18 studies, 690 participants, risk ratio (RR) 0.97, 95% confidence interval (CI)
      0.86 to 1.09) or in acceptability (15 studies, 495 participants, RR of total
      dropout rate 1.02, 95% CI 0.65 to 1.61). Similarly, in comparison with each of
      the other classes of psychological therapies, low-quality evidence showed better
      response to cognitive-behavioural therapies than to behavioural therapies (15
      studies, 544 participants, RR 0.93, 95% CI 0.83 to 1.05) and low-quality evidence
      of better response to behavioural therapies over psychodynamic therapies (2
      studies, 110 participants, RR 1.24, 95% CI 0.84 to 1.82).When compared with
      integrative therapies and humanistic therapies, only one study was included in
      each comparison, and the analysis showed no significant difference between
      behavioural therapies and integrative or humanistic therapies. AUTHORS'
      CONCLUSIONS: We found low- to moderate-quality evidence that behavioural
      therapies and other psychological therapies are equally effective. The current
      evidence base that evaluates the relative benefits and harms of behavioural
      therapies is very weak. This limits our confidence in both the size of the effect
      and its precision for our key outcomes related to response and withdrawal.
      Studies recruiting larger samples with improved reporting of design and fidelity
      to treatment would improve the quality of evidence in this review.

PMID- 24129888
TI  - [Medical conditions of the leg: a clinical synopsis].

PMID- 24129887
TI  - Gene-based therapies in Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurological disorder characterized
      primarily by the degeneration of nigrostriatal dopaminergic neurons and
      diminution of the neurotransmitter dopamine. Though dopamine replacement
      therapies such as levodopa can improve the symptoms of PD, the benefits may be
      overshadowed by side effects and the onset of symptoms not responsive to
      dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and
      cognitive impairment). Furthermore, no therapies have proven to slow the
      neurodegenerative process. Novel approaches to address these difficult problems,
      and others, are being sought. Over the last decade, several innovative gene
      therapies for PD have entered human clinical trials in an effort to address both
      symptomatic and potential disease-modifying effects. Though the results of these
      trials have been mixed, the therapies have generally been safe and well
      tolerated, suggesting gene therapy may be a viable treatment for PD in the
      future. This article will review past and current clinical trials of gene
      therapies for PD. In addition, novel preclinical approaches to gene therapy for
      PD will be described.

PMID- 24129889
TI  - [Leg pain].
AB  - Leg pain is a very common complaint in clinical medicine which deserves thorough
      investigation. All tissues of the lower leg are able to cause pain, each of them
      by different pathomechanisms. In the current review, all the different types of
      tissue, i.e., spine, neural plexus, peripheral nerves, muscles, and vasculature,
      are systematically covered. The different disease entities are explained in terms
      of pathophysiology and clinical picture. Diagnostic measures and pathways are
      sketched, as well as therapeutic approaches in some instances. Diseases of the
      bone and joint are omitted since they are the subject of orthopedic surgery. 

PMID- 24129890
TI  - Modular logic gates: cascading independent logic gates via metal ion signals.
AB  - Systematic cascading of molecular logic gates is an important issue to be
      addressed for advancing research in this field. We have demonstrated that
      photochemically triggered metal ion signals can be utilized towards that goal.
      Thus, independent logic gates were shown to work together while keeping their
      identity in more complex logic designs. Communication through the intermediacy of
      ion signals is clearly inspired from biological processes modulated by such
      signals, and implemented here with ion responsive molecules. 

PMID- 24129891
TI  - IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for
      LPS-TRIF axis.
AB  - Interleukin (IL)-32 is known to exert adujvant effects on innate immune response,
      however, receptors and downstream signaling pathways remain to be clarified. Here
      we found that IL-32gamma upregulated serine protease activity of proteinase-3
      (PR3), in turn triggering protease-activated receptor 2 (PAR2) signaling.
      Interestingly, silencing of PR3 or PAR2 using siRNA markedly diminished IL
      32gamma-induced TNFalpha and IFN-beta mRNA expression. IL-32gamma-PAR2 axis
      utilized TRIF and Ras-Raf-1 pathways. On stimulation with lipopolysaccharide
      (LPS), differential activation of protein kinase C isoforms modulated the balance
      between LPS-TLR4-TRIF and IL-32-PAR2-TRIF axes, because LPS was a strong inducer
      of IL-32gamma. IL-32-PAR2-TRIF axis might serve not only as an extracellular
      sensor of bacterial and autologous proteases, but also as a modulator of innate
      and adaptive immunity during infection. 

PMID- 24129892
TI  - Accelerated electron transport from photosystem I to redox partners by covalently
      linked ferredoxin.
AB  - Photosystem I is a highly efficient and potent light-induced reductase that is
      considered to be an appealing target for integration into hybrid solar fuel
      production systems. However, rapid transport of multiple electrons from the
      reducing end of photosystem I to downstream processes in vivo is limited by the
      diffusion of its native redox partner ferredoxin that is a single electron
      carrier. Here, we describe the design and construction of a faster electron
      transfer interface based on anchoring ferredoxin to the reducing end of
      photosystem I thereby confining the diffusion space of ferredoxin to the near
      vicinity of its photosystem I binding and reduction site. This was achieved by
      fusing ferredoxin to the PsaE subunit of photosystem I by a flexible peptide
      linker and reconstituting PSI in vitro with the new fusion protein. A
      computational algorithm was developed in order to determine the optimal linker
      length that will confine ferredoxin to the vicinity of photosystem I's reducing
      end without restricting the formation of electron transfer complexes. According
      to the calculation, we reconstituted photosystem I with three fusion proteins
      comprising PsaE and ferredoxin separated by linkers of different lengths, namely
      14, 19, and 25 amino acids, and tested their effect on electron transfer rates
      from photosystem I to downstream processes. Indeed, we found a significant
      enhancement of light dependent NADPH synthesis using photosystems containing the
      PsaE-ferredoxin fusion proteins, equivalent to a ten-fold increase in soluble
      ferredoxin concentration. We propose that such a system could be used for other
      ferredoxin dependent redox reactions, such as the enzymatic production of
      hydrogen, a promising alternative fuel. As the system is comprised entirely of
      natural amino acids and biological cofactors, it could be integrated into the
      energy conversion apparatus of photosynthetic organisms by genetic engineering. 

PMID- 24129893
TI  - Characteristics of modern Gleason 9/10 prostate adenocarcinoma: a single tertiary
      centre experience within the Republic of Ireland.
AB  - INTRODUCTION: The 2005 international society of urological pathology consensus
      statement on Gleason grading in prostate cancer revised Gleason scoring in
      clinical practice. The potential for grade migration with this refinement poses
      difficulties in interpreting historical series. We report the characteristics of
      a recent cohort of consecutive Gleason score 9 or 10 prostate cancers in our
      institution. The purpose of this study was to define the clinicopathologic
      variables and staging information for this high-risk population, and to identify
      whether traditional prostate staging techniques are adequate for this subcohort
      of men. MATERIALS AND METHODS: A computational review of our pathology database
      was performed. Between May 2010 and September 2012, 1,295 consecutive biopsies
      were undertaken, 168 of which were high-grade tumours (12.97 %). This group were
      divided into two cohorts of which 84 (12.05 %) had a highest reported Gleason
      score of 9 (N = 79) or 10 (N = 5) and 84 were reported as Gleason 8. All biopsies
      were double-reported by pathologists with a special interest in uropathology.
      RESULTS: Men diagnosed with a Gleason pattern 5 tumour were statistically far
      more likely to have advanced disease on direct rectal examination of the prostate
      compared with Gleason sum 8 tumours (p < 0.001) and a positive first-degree
      family history of prostate cancer (p < 0.001). Overall, Gleason sum 9/10 prostate
      cancers were also found to be statistically more aggressive than Gleason sum 8
      tumours on TRUS core biopsy analysis with significantly higher levels of
      perineural invasion (p < 0.0001) and extracapsular extension (p = 0.001) as well
      as a higher levels of tumour found within the core biopsy sample. Those men
      diagnosed with Gleason pattern 5 prostate cancer also had radiological indicators
      of increased tumour aggressiveness compared with Gleason sum 8 cancer with
      respect to bone (p = 0.0002) and visceral (p = 0.044) metastases at presentation.
      CONCLUSIONS: This series of Gleason score 9/10 prostate cancers serves to
      highlight the large disease burden, adverse pathologic features, and locally
      advanced nature of this aggressive subtype, which has previously been under
      described in the literature, and differs from historical series in having a large
      high-grade cohort demonstrating high rates of metastatic disease. A history of
      prostate cancer amongst first-degree relatives was particularly prevalent in this
      population raising the issue of screening in a high-risk population. The high
      incidence of visceral metastatic disease at presentation supports upfront staging
      with CT thorax, abdomen, and pelvis in patients with Gleason 9 or 10 prostate
      cancers.

PMID- 24129894
TI  - Impact of the type of ultrasound probe on prostate cancer detection rate and
      characterization in patients undergoing MRI-targeted prostate biopsies using
      cognitive fusion.
AB  - PURPOSE: To assess the impact of ultrasound probe (end fire vs. side fire) during
      MRI-targeted prostate biopsy using cognitive fusion. METHODS: Inclusion criteria
      were as follows: consecutive patients undergoing prostate biopsies after
      multiparametric MRI; no PSA above 10 ng/ml; no clinical bulking disease; MRI
      areas suspicious for malignancy. From January 2011 to December 2012, 91 patients
      were included. A standard 10 TRUS-guided biopsy protocol plus 2 targeted biopsies
      at any MRI lesion was used. Patient's characteristics, MRI findings, and
      pathology evaluations were compared between the two groups. RESULTS: Mean patient
      age and PSA were 63 years and 5.95 ng/ml, respectively. The median number of MRI
      lesions was 2, and the mean volume of the index lesion was 0.64 cc. The overall
      PCa detection rate was 58.2 %. The MRI scoring system was significantly
      predictive for PCa detection and aggressiveness (p < 0.001). There was a not
      statistically significant trend toward greater PCa detection rate (+23 %) in the
      end-fire cohort (p = 0.235). The PCa detection rate is significantly improved by
      1.7-fold in case of MRI score 4-5 lesion as compared to MRI score 3 lesion (p =
      0.031) when using the end-fire probe. Conversely, the MRI score does not
      significantly influence the detection rate in the side-fire group (p = 0.250).
      The improvement in the PCa detection rate by the end-fire probe was predominantly
      reported in anterior and of apical peripheral MRI lesions. CONCLUSION: In case of
      high MRI score lesions, the PCa detection rate is significantly improved when
      using end-firing, particularly in case of anterior and apical peripheral lesions.

PMID- 24129895
TI  - When tissue antigens and antibodies get along: revisiting the technical aspects
      of immunohistochemistry--the red, brown, and blue technique.
AB  - Once focused mainly on the characterization of neoplasms, immunohistochemistry
      (IHC) today is used in the investigation of a broad range of disease processes
      with applications in diagnosis, prognostication, therapeutic decisions to tailor
      treatment to an individual patient, and investigations into the pathogenesis of
      disease. This review addresses the technical aspects of immunohistochemistry
      (and, to a lesser extent, immunocytochemistry) with attention to the antigen
      antibody reaction, optimal fixation techniques, tissue processing considerations,
      antigen retrieval methods, detection systems, selection and use of an
      autostainer, standardization and validation of IHC tests, preparation of proper
      tissue and reagent controls, tissue microarrays and other high-throughput
      systems, quality assurance/quality control measures, interpretation of the IHC
      reaction, and reporting of results. It is now more important than ever, with
      these sophisticated applications, to standardize the entire IHC process from
      tissue collection through interpretation and reporting to minimize variability
      among laboratories and to facilitate quantification and interlaboratory
      comparison of IHC results. 

PMID- 24129896
TI  - Leukoencephalomyelopathy of mature captive cheetahs and other large felids: a
      novel neurodegenerative disease that came and went?
AB  - A novel leukoencephalomyelopathy was identified in 73 mature male and female
      large captive felids between 1994 and 2005. While the majority of identified
      cases occurred in cheetahs (Acinonyx jubatus), the disease was also found in
      members of 2 other subfamilies of Felidae: 1 generic tiger (Panthera tigris) and
      2 Florida panthers (Puma concolor coryi). The median age at time of death was 12
      years, and all but 1 cheetah were housed in the United States. Characteristic
      clinical history included progressive loss of vision leading to blindness,
      disorientation, and/or difficulty eating. Neurologic deficits progressed at a
      variable rate over days to years. Mild to severe bilateral degenerative lesions
      were present in the cerebral white matter and variably and to a lesser degree in
      the white matter of the brain stem and spinal cord. Astrocytosis and swelling of
      myelin sheaths progressed to total white matter degeneration and cavitation.
      Large, bizarre reactive astrocytes are a consistent histopathologic feature of
      this condition. The cause of the severe white matter degeneration in these
      captive felids remains unknown; the lesions were not typical of any known
      neurotoxicoses, direct effects of or reactions to infectious diseases, or
      nutritional deficiencies. Leukoencephalomyelopathy was identified in 70 cheetahs,
      1 tiger, and 2 panthers over an 11-year period, and to our knowledge, cases have
      ceased without planned intervention. Given what is known about the epidemiology
      of the disease and morphology of the lesions, an environmental or husbandry
      associated source of neurotoxicity is suspected. 

PMID- 24129897
TI  - Beyond H&E: integration of nucleic acid-based analyses into diagnostic pathology.
AB  - Veterinary pathology of infectious, particularly viral, and neoplastic diseases
      has advanced significantly with the advent of newer molecular methodologies that
      can detect nucleic acid of infectious agents within microscopic lesions,
      differentiate neoplastic from nonneoplastic cells, or determine the suitability
      of a targeted therapy by detecting specific mutations in certain cancers.
      Polymerase chain reaction-based amplification of DNA or RNA and in situ
      hybridization are currently the most commonly used methods for nucleic acid
      detection. In contrast, the main methodology used for protein detection within
      microscopic lesions is immunohistochemistry. Other methods that allow for
      analysis of nucleic acids within a particular cell type or individual cells, such
      as laser capture microdissection, are also available in some laboratories. This
      review gives an overview of the factors that influence the accurate analysis of
      nucleic acids in formalin-fixed tissues, as well as of different approaches to
      detect such targets. 

PMID- 24129898
TI  - Multispectral imaging: a review of its technical aspects and applications in
      anatomic pathology.
AB  - The field of anatomic pathology has changed significantly over the last decades
      and, as a result of the technological developments in molecular pathology and
      genetics, has had increasing pressures put on it to become quantitative and to
      provide more information about protein expression on a cellular level in tissue
      sections. Multispectral imaging (MSI) has a long history as an advanced imaging
      modality and has been used for over a decade now in pathology to improve
      quantitative accuracy, enable the analysis of multicolor immunohistochemistry,
      and drastically reduce the impact of contrast-robbing tissue autofluorescence
      common in formalin-fixed, paraffin-embedded tissues. When combined with advanced
      software for the automated segmentation of different tissue morphologies (eg,
      tumor vs stroma) and cellular and subcellular segmentation, MSI can enable the
      per-cell quantitation of many markers simultaneously. This article covers the
      role that MSI has played in anatomic pathology in the analysis of formalin-fixed,
      paraffin-embedded tissue sections, discusses the technological aspects of why MSI
      has been adopted, and provides a review of the literature of the application of
      MSI in anatomic pathology. 

PMID- 24129899
TI  - A nationwide study on the risk of autoimmune diseases in individuals with a
      personal or a family history of schizophrenia and related psychosis.
AB  - OBJECTIVE: Previous research has found an increased risk of schizophrenia in
      individuals with autoimmune diseases and smaller but significant associations
      with a family history of autoimmune diseases. This study investigates, for the
      first time, the association between schizophrenia and subsequent autoimmune
      diseases (the reverse temporality) and also considers the effect of infections, a
      possible risk factor for both schizophrenia and autoimmune diseases. METHOD:
      Danish nationwide registers were linked to establish a cohort of 3.83 million
      people, identifying 39,364 individuals with schizophrenia-like psychosis and
      142,328 individuals with autoimmune disease. Data were analyzed using survival
      analysis and adjusted for calendar year, age, and sex. RESULTS: Individuals with
      schizophrenia had an elevated risk of subsequent autoimmune diseases, with an
      incidence rate ratio of 1.53 (95% CI=1.46-1.62). Among persons without hospital
      contacts for infections, the effect of having schizophrenia was smaller, with an
      increased incidence rate ratio of 1.32 (95% CI=1.22-1.43) for autoimmune
      diseases. For individuals with schizophrenia as well as hospital contacts for
      infections, the combined risk of autoimmune diseases was 2.70 (95% CI=2.51-2.89).
      A family history of schizophrenia slightly increased the overall risk of
      developing autoimmune diseases (incidence rate ratio=1.06, 95% CI=1.02-1.09).
      Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia,
      and 3.1% of people with autoimmune diseases had a family history of
      schizophrenia. CONCLUSIONS: The increased risk of subsequent autoimmune diseases
      in individuals with schizophrenia may involve neuropsychiatric manifestations
      from the undiagnosed autoimmune disease, medical treatment or lifestyle
      associated with schizophrenia, or common etiological mechanisms, such as
      infections and shared genetic factors.

PMID- 24129900
TI  - Rational and scalable fabrication of high-quality WO3/CdS core/shell nanowire
      arrays for photoanodes toward enhanced charge separation and transport under
      visible light.
AB  - High-quality one-dimensional WO3/CdS core/shell nanowire arrays used as
      photoanodes in photoelectrochemical (PEC) cells were for the first time prepared
      via a rational, two-step chemical vapor deposition process. The narrow band-gap
      CdS shell was homogeneously coated on the entire surface of as-grown WO3 core
      nanowire arrays, forming coaxial heterostructures. The one-dimensional core/shell
      heterostructure facilitates the photogenerated electron-hole pair separation and
      the electron transfer from CdS to WO3 nanowires under visible light illumination.
      Moreover, the core nanowire arrays provide a direct pathway for the electron
      transport. The present results imply that the WO3/CdS core/shell heterostructure
      nanowire arrays may be useful in the design of nanostructure photoanodes toward
      highly efficient PEC cells. 

PMID- 24129901
TI  - Physiological correlates of the big 5: autonomic responses to video
      presentations.
AB  - Personality's link to emotional experience has been demonstrated, but specific
      biological responses to emotion as a function of personality have not been well
      established. Here, the association between personality and physiological
      responses (heart rate, skin conductance, and respiration) to emotional videos was
      assessed. One-hundred sixty-nine participants self-reported on their Big 5
      personality traits and underwent ambulatory monitoring as they watched four brief
      video clips from primetime television content showing scenes containing violence,
      fear, sadness, and tension. Generally, the negatively-toned emotional scenes
      provoked increases in skin conductance response and declines in heart rate. We
      found that physiological outcomes depended on the particular emotional scene and
      on personality, most notably Extraversion and Neuroticism. Extraversion, and to a
      lesser degree, Neuroticism, were associated with increases in autonomic arousal
      responses to the scenes. Gender also interacted with personality to predict
      responses, such that women who scored higher on measures of Extraversion,
      Neuroticism, and Conscientious tended to show more physiological arousal than
      men. Overall, the emotional scenes evoked increases in arousal and more
      controlled attention. The findings are discussed in context of the limited
      capacity model and shed light on how personality and gender affect physiological
      reactions to emotional experiences in everyday life. 

PMID- 24129902
TI  - Cardiovascular effects of acute positive emotional arousal.
AB  - Since there are several popular beliefs about putative health benefits of
      amusement which are empirically substantiated poorly about putative health
      benefits of amusement, the immediate cardiovascular effects of amusement were
      studied in detail. Cardiovascular activity was studied while participants were
      viewing humorous films, relative to a control condition involving no amusement.
      High-resolution measures of heart rate, heart rate variability, continuous blood
      pressure, and respiration were recorded, and the phase synchronization among the
      variables was analyzed, which provides information on the coordinated behavior of
      response systems. Viewing humorous films had cardiovascular effects indicating
      heightened sympathetic arousal, if they elicited intense amusement. No effects
      were observed for variables indicating parasympathetic input to the heart. The
      observed effects associated with amusement were not driven by changes in the
      respiration. The suppression of positive affect expressions did not produce any
      additional activation. The transient cardiovascular effects of amusement do not
      correspond to beneficial correlates of a habitual positive affect disposition
      reported in the literature, demonstrating that it would be erroneous to argue
      from the long-term effects of a positive affect disposition to the effects of a
      single amusing event. 

PMID- 24129903
TI  - Underground allies: how and why do mycelial networks help plants defend
      themselves?: What are the fitness, regulatory, and practical implications of
      defence-related signaling between plants via common mycelial networks?
AB  - Most land plants associate with mycorrhizal fungi that can connect roots of
      neighboring plants in common mycelial networks (CMNs). Recent evidence shows that
      CMNs transfer warning signals of pathogen and aphid attack between plants.
      However, we do not know how defence-related signaling via CMNs operates or how
      ubiquitous it is. Nor do we know what the ecological relevance and fitness
      consequences are, particularly from the perspective of the mycorrhizal fungus.
      Here, we focus on the potential fitness benefits for mycorrhizal fungi and
      outline hypothetical scenarios in which signal transfer via CMNs is modulated in
      order to acquire the most benefit for the fungus (i.e. acquisition of carbon) for
      minimal cost. We speculate that the signal may be quantitative and may elicit
      plant defence responses on different levels depending on the distance the signal
      is transferred. Finally, we discuss the possibility of practical applications of
      this phenomenon for crop protection. 

PMID- 24129904
TI  - Why time matters: codon evolution and the temporal dynamics of dN/dS.
AB  - The ratio of divergence at nonsynonymous and synonymous sites, dN/dS, is a widely
      used measure in evolutionary genetic studies to investigate the extent to which
      selection modulates gene sequence evolution. Originally tailored to codon
      sequences of distantly related lineages, dN/dS represents the ratio of fixed
      nonsynonymous to synonymous differences. The impact of ancestral and lineage
      specific polymorphisms on dN/dS, which we here show to be substantial for closely
      related lineages, is generally neglected in estimation techniques of dN/dS. To
      address this issue, we formulate a codon model that is firmly anchored in
      population genetic theory, derive analytical expressions for the dN/dS measure by
      Poisson random field approximation in a Markovian framework and validate the
      derivations by simulations. In good agreement, simulations and analytical
      derivations demonstrate that dN/dS is biased by polymorphisms at short time
      scales and that it can take substantial time for the expected value to settle at
      its time limit where only fixed differences are considered. We further show that
      in any attempt to estimate the dN/dS ratio from empirical data the effect of the
      intrinsic fluctuations of a ratio of stochastic variables, can even under
      neutrality yield extreme values of dN/dS at short time scales or in regions of
      low mutation rate. Taken together, our results have significant implications for
      the interpretation of dN/dS estimates, the McDonald-Kreitman test and other
      related statistics, in particular for closely related lineages. 

PMID- 24129905
TI  - Situating mortality: quantifying crisis points and periods of stability.
AB  - A wide range of stressors can cause a dramatic and sudden rise in the death rate
      in populations, typically resulting in what is referred to as crisis mortality.
      Here we present a method to standardize the assessment of identifying moments of
      crises. A modification of the mortality Z-score methodology which is combined
      with time series analysis was used to investigate mortality events over the
      course of nearly two centuries for two populations: Gibraltar and Malta. A
      benefit of this method is that it situates the yearly death rate within the
      prevailing mortality pattern, and by doing so allows the researcher to assess the
      relative impact of that event against the norm for the period under
      investigation. A series of threshold values were established to develop levels of
      mortality to distinguish moments of lower mortality than expected, background
      mortality, a crisis, and a catastrophe. Our findings suggested that within
      defined periods, a limited number of events constituted moments of excessive
      mortality in the range of a crisis or higher. These included epidemics (yellow
      fever and influenza in Gibraltar only, and cholera) and casualties associated
      with World War II. Episodes of lower than expected mortality were only detected
      (although not significant) in the 20th century in Malta, and at the micro level,
      the harvesting effect appears to have occurred following cholera epidemics in
      both locations and influenza in Gibraltar. The analysis demonstrates clearly that
      the impact of epidemics can be highly variable across time and populations.

PMID- 24129907
TI  - [Assessment of health-related quality of life in children and adolescents].

PMID- 24129906
TI  - Quantifying SOCE fluorescence measurements in mammalian muscle fibres. The
      effects of ryanodine and osmotic shocks.
AB  - We have quantified Ca(2+) entry through store operated calcium channels in mice
      muscle fibres, measuring the rates of change of myoplasmic [Ca(2+)],
      d[Ca(2+)](myo)/dt, and of Ca(2+) removal, d[Ca(2+)](Removal)/dt, turning store
      operated calcium entry (SOCE) ON, and OFF, by switching on or off external
      Ca(2+). In depleted fibres, poisoned with 10 MUM cyclopiazonic acid SOCE influx
      was about 3 MUM/s. Ryanodine (50 MUM) caused a robust, nifedipine (50 MUM)
      independent, increase in SOCE activation to 8.6 MUM/s. Decreasing medium
      osmolarity from 300 to 220 mOsm/L, decreased SOCE to 0.9 MUM/s, while increasing
      osmolarity from 220 to 400 mOsm/L potentiated SOCE to 43.6 MUM/s. Ryanodine
      inhibited the effects of hypotonicity. Experiments using 2-aminoethoxydiphenyl
      borate, nifedipine, or Mn(2+) quenching, strongly suggest that the increased
      [Ca(2+)](myo) by ryanodine or hypertonic shock is mediated by potentiated SOCE
      activation. The Ca(2+) response decay, quantified by d[Ca(2+)](Removal)/dt,
      indicates a robust residual Ca(2+) removal mechanism in sarco-endoplasmic
      reticulum calcium ATPase poisoned fibres. SOCE high sensitivity to osmotic
      shocks, or to ryanodine receptor (RyR) binding, suggests its high dependency on
      the structural relationship between its molecular constituents, Orai1 and stromal
      interaction molecule and the sarcoplasmic reticulum and plasma membranes, in the
      triadic junctional region, where RyRs, are conspicuously present. This study
      demonstrates that SOCE machinery is highly sensitive to structural changes caused
      by binding of an agonist to its receptor or by imposed osmotical volume changes.

PMID- 24129908
TI  - Effect of HIV clade differences on the onset and severity of HIV-associated
      neurocognitive disorders.
AB  - The effects of evolutionary pressure on human immunodeficiency virus-1 (HIV) have
      resulted in a variety of clades and recombinants. The functional implications of
      HIV clades on disease onset and progression of HIV-associated neurocognitive
      disorders (HAND) have been suggested by clinical and basic science studies, which
      will be reviewed in detail. Some clinical studies suggest that patients infected
      with clade D show the greatest propensity for developing HIV-associated dementia
      (HAD) followed by clades B, C, and A, respectively. However, there are
      conflicting reports. This review summarizes clinical studies that have assessed
      behavioral abnormalities and HIV clade type in HAND patients, focusing on the
      clades stated above. The limitations include variations in testing used to define
      the cohorts, patient sample size, lack of HIV clade characterization, combination
      antiretroviral therapy (cART) availability, and other factors, which are
      highlighted and compared between clinical studies performed primarily in Africa
      and India. Basic science studies provide substantial evidence that HIV clade
      differences can result in varying degrees of neuropathology and are also reviewed
      in some detail. These studies indicate that there are a number of clade
      differences, most notably in Tat, that result in different degrees of
      neurovirulence or neuropathological effects in vitro and in a mouse model of
      HAND. In order to confirm the hypothesis that HIV clade differences are important
      determinants of HAND pathogenesis, larger, longitudinal studies that employ
      standard definitions of HAND and HIV clade testing must be performed. In a larger
      sense, HAND continues to be highly prevalent despite the advent of cART, and
      therefore, further studies into HAND pathogenesis are critical to develop better
      therapies.

PMID- 24129909
TI  - Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV
      associated neurocognitive disorder.
AB  - We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage
      accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected
      subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA
      level in CD14+ cells >=10 copies/10(6) cells, and cognitive impairment underwent
      ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted
      images, all HIV-infected subjects demonstrated a diffuse "tram track" appearance
      in the perivascular regions of cortical and deep white matter vessels suggesting
      ferumoxytol uptake in monocytes/macrophages. This finding was not present in an
      HIV-seronegative control. While ferumoxytol may have potential as an imaging
      biomarker for monocyte/macrophage accumulation in patients with HAND, future
      study is needed.

PMID- 24129910
TI  - Spatiotemporal drug release visualized through a drug delivery system with
      tunable aggregation-induced emission.
AB  - Tetraphenylethene and doxorubicin are assembled into a self-indicating drug
      delivery system (TD NPs). TD NPs are decomposed into DOX and TPE NPs in lysosome.
      Since TD NPs, TPE NPs and DOX are all fluorescent, the detachment of DOX from TPE
      NPs is accompanied by fluorescence changing. By observing the fluorescence
      changes, the spatiotemporal drug release is visualized. 

PMID- 24129911
TI  - 'Do It Yourself' in the parent-professional partnership for the assessment and
      diagnosis of children with autism spectrum conditions in Hong Kong: a qualitative
      study.
AB  - Timely and appropriate care for children with autism spectrum conditions is
      affected by the interaction between healthcare professionals and parents. Despite
      the importance of the parent-professional partnership, there is a dearth of
      cultural-specific data on parent-professional partnership in the Chinese context.
      We conducted 10 in-depth life-history interviews with parents of children with
      autism spectrum conditions in Hong Kong who were diagnosed during preschool
      years. Using an interpretative phenomenological analytic method, five themes were
      constructed to represent the context of parent-professional partnership in Hong
      Kong along the pathway of seeking a diagnosis: (a) access to the assessment and
      diagnosis of autism spectrum conditions, (b) multiple procedures of assessment,
      (c) consultation prior to diagnosis and assessment, (d) communication of
      diagnosis and assessment result and (e) post-assessment isolation. Parental
      narratives highlight the important domains of parent-professional partnership and
      reflect the complexity of diagnosis and the lack of a cohesive system. For many
      parents, the assessment procedure was marred by a series of obstacles, which were
      further exacerbated by a poorly developed parent-professional partnership.
      Suggestions for parent-professional partnership development include establishing
      an evidence-based best practice guideline for Hong Kong, creating pre-assessment
      information workshops for parents to attend and equipping professionals with
      knowledge about autism spectrum conditions and enhanced communication skills. 

PMID- 24129912
TI  - The uses of cognitive training technologies in the treatment of autism spectrum
      disorders.
AB  - In this review, we focus on research that has used technology to provide
      cognitive training - i.e. to improve performance on some measurable aspect of
      behaviour - in individuals with autism spectrum disorders. We review technology
      enhanced interventions that target three different cognitive domains: (a) emotion
      and face recognition, (b) language and literacy, and (c) social skills. The
      interventions reviewed allow for interaction through different modes, including
      point-and-click and eye-gaze contingent software, and are delivered through
      diverse implementations, including virtual reality and robotics. In each case, we
      examine the evidence of the degree of post-training improvement observed
      following the intervention, including evidence of transfer to altered behaviour
      in ecologically valid contexts. We conclude that a number of technological
      interventions have found that observed improvements within the computerised
      training paradigm fail to generalise to altered behaviour in more naturalistic
      settings, which may result from problems that people with autism spectrum
      disorders experience in generalising and extrapolating knowledge. However, we
      also point to several promising findings in this area. We discuss possible
      directions for future work. 

PMID- 24129913
TI  - Imaging dehydration kinetics of a channel hydrate form of the HIV-1 attachment
      inhibitor prodrug BMS-663068.
AB  - An analysis of the free acid form of the HIV-1 attachment inhibitor prodrug BMS
      663068-01 revealed a reversible moisture sorption event in the 42%-46% relative
      humidity (RH) range. An existing single-crystal analysis indicated that these
      observations were due to the formation of a nonstoichiometric channel hydrate.
      This effect was reproducible on repeated cycles, suggesting that the material's
      structural integrity was not compromised because of the interconversion process.
      Small, reversible, and predictable changes in the atomic structure were observed
      by solid-state nuclear magnetic resonance (ssNMR). Atomic force microscopy (AFM)
      and environmental scanning electron microscopy (ESEM) could discern changes in
      surface topography as a function of RH. Surface cracks were visible at 25% RH,
      most of which disappeared at 60% RH. This change was reversible on reducing the
      RH, with cracks reappearing in the same locations. A reduction in surface
      roughness was seen at high humidity, which was consistent with the uptake of
      moisture causing surface swelling. The observations by AFM/ESEM were consistent
      with the atomic alterations seen with ssNMR. Changes in unit cell dimensions are
      not uncommon with channel hydrates as the crystal lattice expands or contracts
      when the crystal structure absorbs/desorbs water, but concomitant, reversible
      surface morphology property changes have not been widely reported.

PMID- 24129914
TI  - Recombinant human kallistatin inhibits angiogenesis by blocking VEGF signaling
      pathway.
AB  - Kallistatin has been recognized as an endogenous angiogenic inhibitor. However,
      the underlying molecular mechanism remains poorly understood. Taking it into
      account that vascular endothelial growth factor (VEGF) has been implicated in all
      aspects of normal and pathological vasculogenesis and angiogenesis. In this
      study, we investigated whether VEGF signaling pathway was impacted by the anti
      angiogenic effect of recombinant human kallistatin (rhKal). We found that the
      rhKal inhibited proliferation as well as induced apoptosis of cultured human
      umbilical vein endothelial cells (HUVECs) in both concentration- and time
      dependent manners. The rhKal also suppressed the VEGF-induced migration and tube
      formation of HUVECs. Furthermore, our data revealed that the rhKal suppressed the
      VEGF165-stimulated tyrosine phosphorylation of VEGFR-2 as well as its downstream
      signal molecular activation. The inhibition of receptor phosphorylation was
      correlated with a decrease in VEGF-triggered phosphorylation of angiogenesis
      signal molecules AKT and ERK, but not stress-related JNK. Taken together, these
      findings added the knowledge for us to understand the anti-angiogenic mechanism
      of kallistatin, which suggested that the rhKal could be worth as a candidate
      compound for further development for the purpose of anti-angiogenic therapies.

PMID- 24129915
TI  - Strong enhancement of luminescence from an iridium polypyridyl complex via
      encapsulation in cucurbituril.
AB  - An exceptional, temperature-dependent enhancement of luminescence is reported
      upon encapsulation of an iridium(III) polypyridyl complex in cucurbit[10]uril
      (Q[10]). This is the first demonstrated example of a luminescent transition metal
      complex occupying the Q[10] cavity with this type of differential response.

PMID- 24129916
TI  - [Prevention of psychotic disorders].
AB  - Psychotic disorders set the first example that prediction and prevention programs
      of modern medicine can also be successfully applied to central psychiatric
      disorders. In the last 20 years criteria for the detection of high-risk states
      prior to the first onset of the disease have been worked out and the predictive
      power for the transition into psychosis has been confirmed. In the centers for
      early recognition and prevention, persons seeking help and advice can now be
      classified into individuals in an early or late high-risk stage by means of newly
      developed instruments. New possibilities of risk stratification ensure a more
      individualized selection of appropriate preventive measures. The interventions
      provided aim at improving risk symptoms, preventing psychosocial disabilities and
      in particular preventing or at least delaying the onset of psychosis. Proof of
      efficacy is so far available for newly developed psychotherapeutic methods,
      neuroprotective agents and low dosage antipsychotics. Prior to administration
      careful risk-benefit analyses have to be carried out for each individual case. 

PMID- 24129917
TI  - [Glaucoma and dry eye. Current concepts and future perspectives].
AB  - PURPOSE: Current concepts and future perspectives for therapy and prevention of
      dry eye in glaucoma patients are described. METHODS: Own clinical and
      experimental findings and PubMed based literature search (keywords: glaucoma and
      dry eye). RESULTS: Ocular surface disease is the main long-term complication of
      glaucoma therapy. Prevention of ocular surface inflammation by preservative-free
      antiglaucoma eye drops and concurrent dry eye therapy are important CONCLUSIONS:
      It is mandatory to treat dry eye prior to and during glaucoma therapy.
      Preservative-free glaucoma medication can help to ameliorate the problem.

PMID- 24129918
TI  - A new near infrared photosensitizing nanoplatform containing blue-emitting up
      conversion nanoparticles and hypocrellin A for photodynamic therapy of cancer
      cells.
AB  - The utilization of up-conversion nanoparticles (UCNPs) for photodynamic therapy
      (PDT) has gained significant interest due to their unique ability to convert near
      infrared light to UV/visible light. Previous work mainly focused on the
      fabrication of green and red emitting UCNPs to load photosensitizers (PSs) for
      PDT. In this work, we firstly developed a new multifunctional nanoplatform
      combining blue-emitting UCNPs with blue-light excited PS (hypocrellin A, HA) as a
      NIR photosensitizing nanoplatform for PDT of cancer cells. Tween 20 coated
      NaYbF4:Tm, Gd@NaGdF4 UCNPs (Tween 20-UCNPs) with strong blue up-conversion
      luminescence and good water dispersibility were prepared for use as PS carriers.
      The blue emission band matched well with the efficient absorption band of HA,
      thereby facilitating the resonance energy transfer from UCNPs to HA and then
      activating HA to produce singlet oxygen ((1)O2). The in vitro study showed that
      these Tween 20-UCNPs@HA complexes could efficiently produce (1)O2 to kill cancer
      cells under 980 nm NIR excitation. Moreover, these Gd(3+) and Yb(3+) containing
      nanoparticles also exhibited positive contrast effects in both T1 weighted
      magnetic resonance imaging (MRI) and computed tomography (CT) imaging, making
      them become a multifunctional platform for simultaneous PDT and bio-imaging. 

PMID- 24129919
TI  - Electromechanics in MoS2 and WS2: nanotubes vs. monolayers.
AB  - The transition-metal dichalcogenides (TMD) MoS2 and WS2 show remarkable
      electromechanical properties. Strain modifies the direct band gap into an
      indirect one, and substantial strain even induces an semiconductor-metal
      transition. Providing strain through mechanical contacts is difficult for TMD
      monolayers, but state-of-the-art for TMD nanotubes. We show using density
      functional theory that similar electromechanical properties as in monolayer and
      bulk TMDs are found for large diameter TMD single- (SWNT) and multi-walled
      nanotubes (MWNTs). The semiconductor-metal transition occurs at elongations of
      16%. We show that Raman signals of the in-plane and out-of-plane lattice
      vibrations depend significantly and linearly on the strain, showing that Raman
      spectroscopy is an excellent tool to determine the strain of the individual
      nanotubes and hence monitor the progress of nanoelectromechanical experiments in
      situ. TMD MWNTs show twice the electric conductance compared to SWNTs, and each
      wall of the MWNTs contributes to the conductance proportional to its diameter.

PMID- 24129920
TI  - Not only bupivacaine but also propofol is sinking in lipid?

PMID- 24129921
TI  - MRI of knee ligament injury and reconstruction.
AB  - Knee ligament instability may lead to meniscal and chondral damage, resulting in
      early osteoarthritis. Due to its superior soft tissue contrast and avoidance of
      harmful ionizing radiation, MRI has become the most important imaging modality
      for early recognition of structural defects of the knee joint. This review aims
      to the understanding of MRI appearances of knee ligament structures associated
      with knee instability, and to review the common patterns of altered knee
      mechanics that lead to ligament failure. Normal anatomy of the knee ligaments,
      pathologic conditions, and postsurgical appearances of the anterior cruciate
      ligament, posterior cruciate ligament, medial collateral ligament, and
      posterolateral corner are described.

PMID- 24129922
TI  - In vivo proton MR spectroscopy in uterine abscesses.
AB  - It is important to make a rapid diagnosis to provide appropriate treatment,
      however, specific diagnosis of causative organisms of pelvic abscesses on
      conventional MR imaging is difficult. MR spectroscopy provides metabolic
      information noninvasively, and has the potential to characterize etiology of the
      abscesses. The presence of acetate (Ac) peak with or without succinate (Suc) peak
      may suggest anaerobic bacterial infection, whereas the absence of Ac and Suc
      peaks in the spectra may suggest aerobic infection. This report describes two
      cases of uterine pyogenic abscesses, which showed Ac and Suc peaks on in vivo MR
      spectroscopy.

PMID- 24129923
TI  - Involvement of poly(ADP-ribose) polymerase in paraptotic cell death of D.
      discoideum.
AB  - Paraptosis is mediated by several proteins, poly(ADP-ribose) polymerase being one
      of them. D. discoideum lacks caspases thus providing a better system to dissect
      out the role of PARP in paraptosis. The cell death phenotype in unicellular
      eukaryote, D. discoideum is similar to the programmed cell death phenotype of
      multicellular animals. However, the events downstream to the death signal of PCD
      in D. discoideum are yet to be understood. Our results emphasize that oxidative
      stress in D. discoideum lacking caspases leads to PARP activation, mitochondrial
      membrane potential changes, followed by the release of apoptosis inducing factor
      from mitochondria. AIF causes large scale DNA fragmentation, a hallmark feature
      of paraptosis. The role of PARP in paraptosis is reiterated via PARP inhibition
      by benzamide, PARG inhibition by gallotannin and PARP down-regulation, which
      delays paraptosis. PARP, PARG and AIF interplay is quintessential in paraptosis
      of D. discoideum. This is the first report to establish the involvement of PARP
      in the absence of caspase activity in D. discoideum which could be of
      evolutionary significance and gives a lead to understand the caspase independent
      paraptotic mechanism in higher organisms. 

PMID- 24129925
TI  - Radiation-induced microRNA: discovery, functional analysis, and cancer
      radiotherapy.
AB  - MicroRNAs (miRNAs) are small non-protein coding RNA that play an important role
      in gene regulation. These RNA molecules function as post-transcriptional
      regulators. miRNAs bind to complementary sequences on target messenger RNA
      transcripts, usually resulting in translational repression or target mRNA
      degradation and gene silencing. miRNA are abundantly present in all human cells,
      target approximately 60% of all genes, and are able to repress hundreds of
      targets each. Since their discovery in 1993 miRNA are emerging as important
      modulators in cellular pathways such as growth and proliferation, apoptosis,
      carcinogenesis, timing of cell-fate decision, and metabolic pathways. A large
      number of studies have examined the general and specific effects of miRNAs
      perturbation in radiation-exposed cells. These studies include expression
      profiling of miRNA, functional analysis, the role of specific miRNAs in tumor
      radiosensitivity, and targeting miRNA for improved cancer radiotherapy. Other
      studies have explored the involvement of miRNA in radiobiological phenomenon like
      bystander effect. Emerging evidence is establishing that miRNA are involved in
      regulating radiation-induced cellular processes, can be exploited to improve
      cancer radiation therapy, and could serve as biomarkers of human radiation
      exposure.

PMID- 24129924
TI  - Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2
      deficient myotubes.
AB  - Muscle cell apoptosis accompanies normal muscle development and regeneration, as
      well as degenerative diseases and aging. C2C12 murine myoblast cells represent a
      common model to study muscle differentiation. Though it was already shown that
      myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a
      fraction of cells, either the cell population sensitive to apoptosis or
      regulatory mechanisms for the apoptotic response are unclear so far. In the
      current study we characterize apoptotic phenotypes of different types of C2C12
      cells at all stages of differentiation, and report here that myotubes of
      differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are
      particularly vulnerable to apoptosis even though they are displaying low levels
      of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit
      higher levels of Bcl-2 and high resistance to apoptosis. The transfection of
      proliferating myoblasts with Bcl-2 prior to differentiation did not protect
      against spontaneous apoptosis accompanying differentiation of C2C12 cells but led
      to Bcl-2 overexpression in myotubes and to significant protection from apoptotic
      cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for
      a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However,
      downstream processes for spontaneous and hydrogen peroxide induced apoptosis are
      not completely similar. Apoptosis in differentiating myoblasts and myotubes is
      regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family
      proteins such as Bax, Bak, and Bad. 

PMID- 24129926
TI  - Plasma tau as a window to the brain-negative associations with brain volume and
      memory function in mild cognitive impairment and early Alzheimer's disease.
AB  - Neurofibrillary tangles are associated with cognitive dysfunction, and
      hippocampal atrophy with increased CSF tau markers. However, the plasma tau
      levels of Alzheimer's disease (AD) have not been well studied. We investigated
      plasma tau by using an immunomagnetic reduction assay in 20 patients with mild
      cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders
      (HE). All received a 3D-brain MRI scan and a set of cognitive function test. We
      explored their relationships with both brain structure and cognitive functions.
      Images were analyzed to determine the brain volumes and gray matter densities.
      Patients with MCI or early AD had significantly increased plasma tau levels
      compared with HE. Plasma tau levels were negatively associated with the
      performance of logical memory, visual reproduction, and verbal fluency; also
      negatively associated with volume of total gray matter, hippocampus, amygdala;
      and gray matter densities of various regions. Regression analyses indicated that
      logical memory explained 0.394 and hippocampus volume predicted .608 of the
      variance of plasma tau levels, both P < 0.001. Education years were negatively
      associated with the gray matter densities of the supramarginal (r = -0.407),
      middle temporal gyrus (r = -0.40) and precuneus (r = -0.377; all P < 0.05) in HE;
      and negatively associated with plasma tau levels in patients (r = -0.626). We
      propose that plasma tau may serve as a window to both structure and function of
      the brain. Higher education is a protective factor against AD and is associated
      with lower plasma tau levels in patients.

PMID- 24129927
TI  - Childhood separation anxiety and the pathogenesis and treatment of adult anxiety.
AB  - Clinically significant separation anxiety disorder in childhood leads to adult
      panic disorder and other anxiety disorders. The prevailing pathophysiological
      model of anxiety disorders, which emphasizes extinction deficits of fear
      conditioned responses, does not fully consider the role of separation anxiety.
      Pathological early childhood attachments have far-reaching consequences for the
      later adult ability to experience and internalize positive relationships in order
      to develop mental capacities for self-soothing, anxiety tolerance, affect
      modulation, and individuation. Initially identified in attachment research, the
      phenomenon of separation anxiety is supported by animal model, neuroimaging, and
      genetic studies. A role of oxytocin is postulated. Adults, inured to their
      anxiety, often do not identify separation anxiety as problematic, but those who
      develop anxiety and mood disorders respond more poorly to both pharmacological
      and psychotherapeutic interventions. This poorer response may reflect patients'
      difficulty in forming and maintaining attachments, including therapeutic
      relationships. Psychotherapies that focus on relationships and separation anxiety
      may benefit patients with separation anxiety by using the dyadic therapist
      patient relationship to recapture and better understand important elements of
      earlier pathological parent-child relationships. 

PMID- 24129928
TI  - [Do German DRGs appropriately explain the resource consumption of hospitals? An
      empirical patient-level cost-data analysis across ten episodes of care].
AB  - AIM OF THE STUDY: The revenues of German hospitals are mainly determined by DRG
      based payments. Therefore DRGs should appropriately explain the resource
      consumption of hospitals in order to avoid unintended consequences. So far little
      is known about the ability of German DRGs to adequately reflect the cost of a
      hospital stay. METHODS: Regression techniques were applied using anonymised year
      2008 cost and performance data of 50,156 cases from 29 hospitals for 10 common
      episodes of care in order a) to analyse the impact of patient and treatment
      characteristics on costs and b) to test if DRG variables are better in explaining
      resource consumption than this set of patient variables. RESULTS: Depending on
      the episode of care, patient and treatment variables have a different impact on
      hospital costs. However, they are better in explaining resource consumption than
      the DRG variables for each episode of care. In addition, independent of the
      patient characteristics hospitals have an impact on costs which might be due to
      factors that are not considered by the DRG-system. CONCLUSION: The analysis shows
      that the German DRG system requires further research. However, to date this is
      limited by poor data availability. Compared to other DRG systems the German
      system shows a weak performance. The incorporation of some of the used variables
      as well as an increasing international knowledge transfer might help to further
      improve the German DRG system.

PMID- 24129930
TI  - A new series: Clinical Dilemmas in Interventional Cardiology.

PMID- 24129929
TI  - Increase in ezrin expression from benign to malignant breast tumours.
AB  - PURPOSE: Ezrin is known to be involved in intercellular interactions, and a shift
      from membrane-bound to cytoplasmatic protein expression has been associated with
      malignant potential. This association has primarily been demonstrated in cell
      lines and, as yet, little is known about the distribution of ezrin in primary
      benign and malignant breast tissues. We have, therefore, set out to investigate
      ezrin protein expression in a series of primary breast lesions. METHODS:
      Immunohistochemistry was used to detect ezrin expression in 465 samples of normal
      breast tissues, benign breast tumours, pre-invasive breast lesions, breast cancer
      tissues and metastatic lymph nodes, and the protein expression patterns observed
      were correlated with clinicopathological parameters. RESULTS: Ezrin was detected
      in the cytoplasm of both benign and malignant breast tissues, but its expression
      was significantly higher in the malignant tissues (13 % vs 60 %, p < 0.0001; chi
      (2) test). We also detected a statistically significant higher ezrin expression
      in pre-invasive lesions compared to benign lesions (15 % vs 44 %, p = 0.04; chi
      (2) test). We did not find such a difference in ezrin expression between pre
      invasive and invasive cancer samples, nor between invasive cancer samples and
      lymph node metastases. Within the group of invasive cancer samples, we found a
      significant correlation between ezrin expression and CK14 (rs:0.38, p < 0.007)
      and Her2 (rs:0.25, p < 0.002) expression. No such correlation was observed
      between ezrin expression and nodal status, grading, patient's age, hormone
      receptor status, and Ki67 or p53 expression. CONCLUSION: Taken together, we found
      that cytoplasmatic ezrin expression increases from benign to malignant breast
      tumour development. We hypothesize that the tissue architectural alterations that
      are associated with aberrant ezrin expression may point at pathophysiological
      mechanisms that may be instrumental for the design of novel therapies.

PMID- 24129931
TI  - Prohealing endothelial progenitor cell capture stents: do the cells captured
      explain the clinical outcomes?

PMID- 24129932
TI  - Operator's experience is the most efficient embolic protection device for carotid
      artery stenting.

PMID- 24129933
TI  - Inferior vena cava filters: truth or dare?

PMID- 24129934
TI  - Fracture of cardiovascular stents in patients with congenital heart disease:
      theoretical and empirical considerations.

PMID- 24129935
TI  - Symptomatic obstructive hypertrophic cardiomyopathy.

PMID- 24129936
TI  - MRI-induced stent dislodgment soon after left main coronary artery stenting.

PMID- 24129938
TI  - Letter by Mangiacapra and Barbato regarding article, "Effects of endothelial
      dysfunction on residual platelet aggregability after dual antiplatelet therapy
      with aspirin and clopidogrel in patients with stable coronary artery disease".

PMID- 24129939
TI  - Response to letter regarding article, "Effects of endothelial dysfunction on
      residual platelet aggregability after dual antiplatelet therapy with aspirin and
      clopidogrel in patients with stable coronary artery disease".

PMID- 24129941
TI  - Body mass index and socioeconomic status measured in adolescence, country of
      origin, and the incidence of gastroesophageal adenocarcinoma in a cohort of 1
      million men.
AB  - BACKGROUND: To the authors' knowledge, little work has been done concerning
      adolescent precursors for gastroesophageal cancer. In the current study, the
      association of adolescent overweight as well as socioeconomic status (SES) with
      the incidence of esophageal adenocarcinoma (EAC), gastroesophageal junction
      adenocarcinoma (GEJAC), and noncardia gastric cancer (NCGC) was evaluated.
      METHODS: Body mass index (BMI) was measured in 1 million Israeli adolescent males
      who underwent a general health examination at a mean age of 17.3 +/- 0.5 years
      from 1967 to 2005. Overweight was defined as a BMI >= 85th percentile of the
      standard US distribution in adolescence. Incident cancer was identified by
      linkage with the Israeli National Cancer Registry. RESULTS: A total of 182
      incident cancer cases were documented (52 combined EAC and GEJAC cases and 130
      NCGC cases). Adolescent overweight at baseline (BMI >= 85th percentile) was
      associated with an increased risk in the combined group of cases of EAC and GEJAC
      (multivariable hazards ratio [HR], 2.1; 95% confidence interval [95% CI], 1.1-4.3
      [P = .032]). Low SES (the lowest category vs the highest) as well as low number
      of years of education (<= 9 years) were associated with an increased risk of
      intestinal-type NCGC (multivariable HR, 2.2; 95% CI, 1.0-4.8 [P = .041] and
      multivariable HR, 1.9; 95% CI, 1.1-3.19 [P = .020], respectively). The adjusted
      risk of NCGC was higher in immigrants born in Asian countries and the former
      Soviet Union. CONCLUSIONS: Overweight during adolescence was found to be
      substantially associated with the subsequent development of EAC and GEJAC. In
      addition, although potential confounding by Helicobacter pylori infection status
      or lifestyle factors was not fully accounted for in the analyses, lower SES as
      well as immigration from higher-risk countries are important determinants of
      NCGC.

PMID- 24129942
TI  - Revisiting catalytic model reaction p-nitrophenol/NaBH4 using metallic
      nanoparticles coated on polymeric spheres.
AB  - The early reported pseudo-first-order reaction kinetics of the polymer-supported
      metallic nanocatalysts for the model reaction of p-nitrophenol (p-NP)/NaBH4 were
      probably oversimplified. Here a detailed study of p-NP reduction by NaBH4 in the
      presence of the raspberry-like poly(allylamine hydrochloride)-modified polymer
      poly(glycidyl methacrylate) composite sub-microspheres with tunable gold
      nanoparticles (PGMA@PAH@AuNPs) was presented. Effects of polyelectrolyte
      concentration, the ratio of polymer spheres to gold nanoparticles, and the
      solution pH value for composite synthesis on the induction period, reaction time,
      average reaction rate and average turnover frequency were systematically
      investigated. Experimental results in all cases of our study revealed an n(th)
      order (n > 1) of the p-NP/NaBH4 catalytic reaction by the prepared polymer
      composite particles. The apparent order of reaction, n, is dependent on the total
      surface area of the coated gold nanoparticles on the polymer spheres, which can
      be closely correlated with the tunable gold nanoparticle surface coverage. The
      mechanism of the observed catalytic activity enhancement was proposed based on
      active epoxy groups of the polymer spheres and a large adsorption of p
      nitrophenolate anions onto the positively-charged spheres. 

PMID- 24129940
TI  - Death by transposition - the enemy within?
AB  - Here we present and develop the hypothesis that the derepression of endogenous
      retrotransposable elements (RTEs) - "genomic parasites" - is an important and
      hitherto under-unexplored molecular aging process that can potentially occur in
      most tissues. We further envision that the activation and continued presence of
      retrotransposition contribute to age-associated tissue degeneration and
      pathology. Chromatin is a complex and dynamic structure that needs to be
      maintained in a functional state throughout our lifetime. Studies of diverse
      species have revealed that chromatin undergoes extensive rearrangements during
      aging. Cellular senescence, an important component of mammalian aging, has
      recently been associated with decreased heterochromatinization of normally
      silenced regions of the genome. These changes lead to the expression of RTEs,
      culminating in their transposition. RTEs are common in all kingdoms of life, and
      comprise close to 50% of mammalian genomes. They are tightly controlled, as their
      activity is highly destabilizing and mutagenic to their resident genomes. 

PMID- 24129943
TI  - Catalysis by coke deposits: synthesis of isoprene over solid catalysts.
AB  - A help rather than a hindrance: Carbonaceous deposits have been found to play a
      key role in the selective synthesis of isoprene from formaldehyde and isobutene
      over solid catalysts. They accumulate on the catalyst surface during the
      induction period and promote the interaction of the substrates at the steady
      state. The proposed mechanism shows the way forward for the design of efficient
      solid catalysts for the synthesis of isoprene. 

PMID- 24129944
TI  - Species-specific responses of N homeostasis and electrolyte handling to low N
      intake: a comparative physiological approach in a monogastric and a ruminant
      species.
AB  - In our former studies low crude protein (LCP) intake influenced N homeostasis and
      electrolyte handling in goats. We hypothesised that due to rumino-hepatic
      nitrogen (N) recycling adaptation of N homeostasis and adjustment of electrolyte
      handling to LCP intake differs between goats and monogastric animals. Therefore,
      an experiment similar to that with goats was conducted with rats. Two feeding
      groups received a diet either containing 20 or 8 % crude protein (as fed basis)
      for 5 weeks and intake and excretion of N, calcium (Ca) and phosphorus (P) were
      determined. To detect systemic and endocrine adaptation to LCP intake plasma
      concentrations of urea, Ca, phosphate (Pi), insulin-like growth factor 1 (IGF-1),
      1,25-dihydroxyvitamin D3 (calcitriol), parathyroid hormone (PTH) and cross-linked
      telopeptide of type I collagen (CTX) were measured. Adjustment of renal
      electrolyte transport was assessed by detecting protein expression of key
      proteins of renal Pi transport. All data were compared with the data of the goat
      experiment. LCP intake decreased plasma urea concentration stronger in goats than
      in rats. In both species urinary N excretion declined, but faecal N excretion
      decreased in goats only. Furthermore, in goats urinary Ca excretion decreased,
      but in rats urinary Ca concentration increased. Decreased plasma IGF-1 and
      calcitriol concentrations were found in goats only. Thus, renal Ca excretion
      appears to be a common target in adaptation of electrolyte homeostasis in both
      species, but is regulated differently.

PMID- 24129945
TI  - Polyunsaturated fats, membrane lipids and animal longevity.
AB  - Fatty acids are essential for life because they are essential components of
      cellular membranes. Lower animals can synthesize all four classes of fatty acids
      from non-lipid sources, but both omega-6 and omega-3 cannot be synthesized de
      novo by 'higher' animals and are therefore essential components of their diet.
      The relationship between normal variation in diet fatty acid composition and
      membrane fatty acid composition is little investigated. Studies in the rat show
      that, with respect to the general classes of fatty acids (saturated,
      monounsaturated and polyunsaturated) membrane fatty acid composition is
      homeostatically regulated despite diet variation. This is not the case for fatty
      acid composition of storage lipids, which responds to diet variation.
      Polyunsaturated fatty acids are important determinants of physical and chemical
      properties of membranes. They are the substrates for lipid peroxidation and it is
      possible to calculate a peroxidation index (PI) for a particular membrane
      composition. Membrane PI appears to be homeostatically regulated with respect to
      diet PI. Membrane fatty acid composition varies among species and membrane PI is
      inversely correlated to longevity in mammals, birds, bivalve molluscs, honeybees
      and the nematode Caenorhabditis elegans. 

PMID- 24129946
TI  - Development of a stable virus-like particle vaccine formulation against
      Chikungunya virus and investigation of the effects of polyanions.
AB  - Chikungunya virus (CHIKV) is an alphavirus that infects millions of people every
      year, especially in the developing world. The selective expression of recombinant
      CHIKV capsid and envelope proteins results in the formation of self-assembled
      virus-like particles (VLPs) that have been shown to protect nonhuman primates
      against infection from multiple strains of CHIKV. This study describes the
      characterization, excipient screening, and optimization of CHIKV VLP solution
      conditions toward the development of a stable parenteral formulation. The CHIKV
      VLPs were found to be poorly soluble at pH 6 and below. Circular dichroism,
      intrinsic fluorescence, and static and dynamic light scattering measurements were
      therefore performed at neutral pH, and results consistent with the formation of
      molten globule structures were observed at elevated temperatures. A library of
      generally recognized as safe excipients was screened for their ability to
      physically stabilize CHIKV VLPs using a high-throughput turbidity-based assay.
      Sugars, sugar alcohols, and polyanions were identified as potential stabilizers
      and the concentrations and combinations of select excipients were optimized. The
      effects of polyanions were further studied, and while all polyanions tested
      stabilized CHIKV VLPs against aggregation, the effects of polyanions on
      conformational stability varied.

PMID- 24129947
TI  - Noncontrast dynamic 3D intracranial MR angiography using pseudo-continuous
      arterial spin labeling (PCASL) and accelerated 3D radial acquisition.
AB  - PURPOSE: To develop a novel dynamic 3D noncontrast magnetic resonance angiography
      (MRA) technique that combines dynamic pseudo-continuous arterial spin labeling
      (dynamic PCASL), accelerated 3D radial sampling (VIPR), and time-of-arrival (TOA)
      mapping to provide quantitative assessment of arterial flow. MATERIALS AND
      METHODS: Digital simulations were performed to investigate the effects of
      acquisition scheme and sequence parameters on image quality and TOA mapping
      fidelity. Five patients with vascular malformations (arteriovenous malformation
      [AVM] = 3, dural arteriovenous fistula [DAVF] = 2) were scanned and the images
      were compared to digital subtraction angiography (DSA) for the ability to
      identify the arterial supply, AVM location, nidus size, and venous drainage.
      RESULTS: Digital simulations demonstrated reduced image artifacts and improved
      TOA accuracy using radial acquisition over Cartesian. TOA mapping accuracy is
      more sensitive to sampling window length than time spacing. Dynamic PCASL MRA
      depicted seven of eight arterial pedicles, and accurately measured the AVM nidus
      size when the nidus was compact. The venous drainage in the AVM patients was not
      consistently visualized. CONCLUSION: Dynamic 3D PCASL-VIPR with TOA mapping is
      able to acquire both high temporal and spatial resolution inflow dynamics that
      could improve diagnosis of high-flow intracranial vascular diseases.

PMID- 24129948
TI  - Relationships between cardiorespiratory fitness, metabolic control, and fat
      distribution in type 2 diabetes subjects.
AB  - Factors contributing to the reduced cardiorespiratory fitness typical of
      sedentary subjects with type 2 diabetes are still largely unknown. In this study,
      we assessed the relationships between cardiorespiratory fitness and abdominal and
      skeletal muscle fat content in 39 untrained type 2 diabetes subjects, 27 males
      and 12 females (mean +/- SD age 56.5 +/- 7.3 year, BMI 29.4 +/- 4.7 kg/m(2)).
      Peak oxygen uptake (VO2peak) and ventilatory threshold (VO2VT) were assessed by
      maximal cycle ergometer exercise test, insulin sensitivity by euglycemic
      hyperinsulinemic clamp, and body composition by dual-energy X-ray absorptiometry.
      Magnetic resonance imaging was used to evaluate visceral, total subcutaneous
      (SAT), superficial (SSAT) and deep sub-depots of subcutaneous abdominal adipose
      tissue, and sagittal abdominal diameter (SAD), as well as femoral quadriceps
      skeletal muscle fat content. In univariate analysis, both VO2peak and VO2VT were
      inversely associated with BMI, total fat mass, SAT, SSAT, and sagittal abdominal
      diameter. VO2peak was also inversely associated with skeletal muscle fat content.
      A significant direct association was observed between VO2VT and insulin
      sensitivity. No associations between cardiorespiratory fitness parameters and
      metabolic profile data were found. In multivariable regression analysis, after
      adjusting for age and gender, VO2peak was independently predicted by higher HDL
      cholesterol, and lower SAD and skeletal muscle fat content (R (2) = 0.64, p <
      0.001), whereas VO2VT was predicted only by sagittal abdominal diameter (R (2) =
      0.48, p = 0.025). In conclusion, in untrained type 2 diabetes subjects, peak
      oxygen uptake is associated with sagittal abdominal diameter, skeletal muscle fat
      content, and HDL cholesterol levels. Future research should target these features
      in prospective intervention studies. 

PMID- 24129949
TI  - Surfactant-thermal method to synthesize a novel two-dimensional oxochalcogenide.
AB  - A new two-dimensional (2D) oxosulfide, (N2H4)2Mn3Sb4S8(MU3-OH)2 (1), has been
      successfully synthesized under surfactant-thermal conditions with
      hexadecyltributylphosphonium bromide as the surfactant. Compound 1 has a layered
      structure and contains a novel [Mn3(MU3-OH)2]n chain along the b-axis. The
      photocatalytic activity for compound 1 has been demonstrated under visible-light
      irradiation and continuous H2 evolution was observed. Our results indicate that
      surfactant-thermal synthesis could be a promising method for growing novel
      crystalline oxochalcogenides with interesting structures and properties.

PMID- 24129950
TI  - Sage in vitro cultures: a promising tool for the production of bioactive terpenes
      and phenolic substances.
AB  - Extracts of Salvia species are used in traditional medicine to treat various
      diseases. The economic importance of this genus has increased in recent years due
      to evidence that some of its secondary metabolites have valuable pharmaceutical
      and nutraceutical properties.The bioactivity of sage extracts is mainly due to
      their content of terpenes and polyphenols. The increasing demand for sage
      products combined with environmental, ecological and climatic limitations on the
      production of sage metabolites from field-grown plants have led to extensive
      investigations into biotechnological approaches for the production of Salvia
      phytochemicals. The purpose of this review is to evaluate recent progress in
      investigations of sage in vitro systems as tools for producing important
      terpenoids and polyphenols and in development of methods for manipulating
      regulatory processes to enhance secondary metabolite production in such systems. 

PMID- 24129951
TI  - Enantioselective hydrolysis of racemic styrene oxide and its substituted
      derivatives using newly-isolated Sphingopyxis sp. exhibiting a novel epoxide
      hydrolase activity.
AB  - (S)-Styrene oxide, (S)-2-chlorostyrene oxide (CSO), (S)-3-CSO and (S)-4-CSO with
      99.9 %ee were obtained with a yield of 20.6, 39.3, 28.7 and 26.8 % from 4 mM
      corresponding racemic substrates using 10 mg cells of a newly-isolated
      Sphingopyxis sp. at pH 8.0 and 25  degrees C in 1 ml 100 mM Tris/HCl buffer after
      420, 100, 120 and 55 min, respectively. For racemic 2CSO, well-known for one of
      the racemates that is difficult to obtained in enantiomerically pure form, (S)-2
      CSO with 99.9 %ee, 39.3 % yield (theoretical yield 50 %) and enantiomeric ratio
      of 42.1 was obtained. The newly-isolated strain can thus be used as whole-cell
      biocatalyst in the production of various (S)-CSO with a chlorine group at
      different positions. 

PMID- 24129952
TI  - Imaging the hard/soft tissue interface.
AB  - Interfaces between different tissues play an essential role in the biomechanics
      of native tissues and their recapitulation is now recognized as critical to
      function. As a consequence, imaging the hard/soft tissue interface has become
      increasingly important in the area of tissue engineering. Particularly as several
      biotechnology based products have made it onto the market or are close to human
      trials and an understanding of their function and development is essential. A
      range of imaging modalities have been developed that allow a wealth of
      information on the morphological and physical properties of samples to be
      obtained non-destructively in vivo or via destructive means. This review
      summarizes the use of a selection of imaging modalities on interfaces to date
      considering the strengths and weaknesses of each. We will also consider
      techniques which have not yet been utilized to their full potential or are likely
      to play a role in future work in the area. 

PMID- 24129953
TI  - Improved succinate production in Corynebacterium glutamicum by engineering
      glyoxylate pathway and succinate export system.
AB  - A dual route for anaerobic succinate production was engineered into
      Corynebacterium glutamicum. The glyoxylate pathway was reconstructed by
      overexpressing isocitrate lyase, malate synthase and citrate synthase. The
      engineered strain produced succinate with a yield of 1.34 mol (mol glucose)(-1).
      Further overexpression of succinate exporter, SucE, increased succinate yield to
      1.43 mol (mol glucose)(-1). Metabolic flux analysis revealed that the glyoxylate
      pathway was further activated by engineering succinate export system. Using an
      anaerobic fed-batch fermentation process, the final strain produced 926 mM
      succinate (= 109 g l(-1)) with an overall volumetric productivity of 9.4 mM h(-1)
      and an average yield of 1.32 mol (mol glucose)(-1).

PMID- 24129954
TI  - From genomics to functional markers in the era of next-generation sequencing.
AB  - The availability of complete genome sequences, along with other genomic resources
      for Arabidopsis, rice, pigeon pea, soybean and other crops, has revolutionized
      our understanding of the genetic make-up of plants. Next-generation DNA
      sequencing (NGS) has facilitated single nucleotide polymorphism discovery in
      plants. Functionally-characterized sequences can be identified and functional
      markers (FMs) for important traits can be developed at an ever-increasing ease.
      FMs are derived from sequence polymorphisms found in allelic variants of a
      functional gene. Linkage disequilibrium-based association mapping and homologous
      recombinants have been developed for identification of "perfect" markers for
      their use in crop improvement practices. Compared with many other molecular
      markers, FMs derived from the functionally characterized sequence genes using NGS
      techniques and their use provide opportunities to develop high-yielding plant
      genotypes resistant to various stresses at a fast pace. 

PMID- 24129955
TI  - Method for assembling and expressing multiple genes in the nucleus of microalgae.
AB  - The green alga, Chlamydomonas reinhardtii, is a model organism used in the study
      of photosynthesis and biotechnological research. Despite its importance, a
      complete set of genetic tools has yet to be developed. Here, we report the
      development of a new method for constructing a multi-gene pathway in
      Saccharomyces cerevisiae and integrating the assembled pathway into the nuclear
      genome of C. reinhardtii. To demonstrate the use of this method, we assembled and
      functionally expressed up to three reporter proteins (Ble, AphVIII, and GFP)
      simultaneously in the nucleus of C. reinhardtii. This new molecular tool should
      aid efforts to engineer microalgae for biofuel and biopharmaceutical production. 

PMID- 24129956
TI  - Co-expression for intracellular processing in microbial protein production.
AB  - The biological activity of a recombinant protein is highly dependent on its
      biophysical properties including post-translational modifications, solubility,
      and stability. Production of active recombinant proteins requires careful design
      of the expression strategy and purification schemes. This is often achieved by
      proper modification of the target protein during and/or after protein synthesis
      in the host cells. Such co-translational or post-translational processing of
      recombinant proteins is typically enabled by co-expressing the required enzymes,
      folding chaperones, co-factors and/or processing enzymes in the host. Various
      applications of the co-expression technology in protein production are discussed
      in this review with representative examples described. 

PMID- 24129957
TI  - A microscale anisotropic biaxial cell stretching device for applications in
      mechanobiology.
AB  - A multi-layered polydimethylsiloxane microfluidic device with an integrated
      suspended membrane has been fabricated that allows dynamic and multi-axial
      mechanical deformation and simultaneous live-cell microscopy imaging. The
      transparent membrane's strain field can be controlled independently along two
      orthogonal directions. Human foreskin fibroblasts were immobilized on the
      membrane's surface and stretched along two orthogonal directions sequentially
      while performing live-cell imaging. Cyclic deformation of the cells induced a
      reversible reorientation perpendicular to the direction of the applied strain.
      Cells remained viable in the microdevice for several days. As opposed to existing
      microfluidic or macroscale stretching devices, this device can impose changing,
      anisotropic and time-varying strain fields in order to more closely mimic the
      complexities of strains occurring in vivo. 

PMID- 24129958
TI  - Lectin of Abelmoschus esculentus (okra) promotes selective antitumor effects in
      human breast cancer cells.
AB  - The anti-tumor effects of a newly-discovered lectin, isolated from okra,
      Abelmoschus esculentus (AEL), were investigated in human breast cancer (MCF7) and
      skin fibroblast (CCD-1059 sk) cells. AEL induced significant cell growth
      inhibition (63 %) in MCF7 cells. The expression of pro-apoptotic caspase-3,
      caspase-9, and p21 genes was increased in MCF7 cells treated with AEL, compared
      to those treated with controls. In addition, AEL treatment increased the Bax/Bcl
      2 ratio in MCF7 cells. Flow cytometry also indicated that cell death (72 %)
      predominantly occurred through apoptosis. Thus, AEL in its native form promotes
      selective antitumor effects in human breast cancer cells and may represent a
      potential therapeutic to combat human breast cancer.

PMID- 24129959
TI  - Selective exo-enzymatic labeling of N-glycans on the surface of living cells by
      recombinant ST6Gal I.
AB  - A game of tag: N-Glycans on the surface of living cells were selectively tagged
      by exogenously administering recombinant ST6Gal I sialyltransferase and azide
      modified CMP-Neu5Ac. This modification was followed by a strain-promoted
      cycloaddition using a biotin-modified dibenzylcyclooctynol (red star=biotin). The
      methodology will make it possible to dissect the mechanisms that underlie altered
      glycoconjugate recycling and storage in disease. 

PMID- 24129960
TI  - An adaptive, comprehensive monitoring strategy for chemicals of emerging concern
      (CECs) in California's Aquatic Ecosystems.
AB  - A scientific advisory panel was convened by the State of California to recommend
      monitoring for chemicals of emerging concern (CECs) in aquatic systems that
      receive discharge of municipal wastewater treatment plant (WWTP) effluent and
      stormwater runoff. The panel developed a risk-based screening framework that
      considered environmental sources and fate of CECs observed in receiving waters
      across the State. Using existing occurrence and risk threshold data in water,
      sediment, and biological tissue, the panel applied the framework to identify a
      priority list of CECs for initial monitoring in three representative receiving
      water scenarios. The initial screening list of 16 CECs identified by the panel
      included consumer and commercial chemicals, flame retardants, pesticides,
      pharmaceuticals and personal care products, and natural hormones. The panel
      designed an iterative, phased strategy with interpretive guidelines that direct
      and update management actions commensurate with potential risk identified using
      the risk-based framework and monitoring data. Because of the ever-changing nature
      of chemical use, technology, and management practices, the panel offered
      recommendations to improve CEC monitoring, including development of bioanalytical
      screening methods whose responses integrate exposure to complex mixtures and that
      can be linked to higher-order effects; development or refinement of models that
      predict the input, fate, and effects of future chemicals; and filling of key data
      gaps on CEC occurrence and toxicity. Finally, the panel stressed the need for
      adaptive management, allowing for future review of, and if warranted,
      modifications to the strategy to incorporate the latest science available to the
      water resources community.

PMID- 24129961
TI  - Self-grown oxy-hydroxide@ nanoporous metal electrode for high-performance
      supercapacitors.
AB  - A binder-free self-grown oxy-hydroxide@nanoporous Ni-Mn hybrid electrode with
      high capacitance and cyclic stability is fabricated by electrochemical
      polarization of a dealloyed nanoporous Ni-Mn alloy. Combined with the low
      material costs, high electrochemical stability, and environmentally friendly
      nature, this novel electrode holds great promise for applications in high
      capacity commercial supercapacitors. 

PMID- 24129962
TI  - Cyclopalladated complexes derived from benzamidoxime.
AB  - Cyclopalladated benzamidoxime complexes [Pd{C,N-C6H4{C(NH2)[double bond, length
      as m-dash]NOH}-2}Cl(L)] (L = PTol3, Tol = C6H4Me-4 (); XyNC, Xy = C6H3Me2-2,6 ();
      pic, C5H4Me-4 ()), [Pd{C,N-C6H4{C(NH2)[double bond, length as m-dash]NOH}
      2}(L2)]ClO4 (L = pic (); L2 = 4,4'-di-tert-butyl-2,2'-bipyridine, tbbpy ()) and
      PPN[Pd{C,N-C6H4{C(NH2)[double bond, length as m-dash]NOH}-2}Cl2] () are prepared
      by reacting [Pd{C,N-C6H4{C(NH2)[double bond, length as m-dash]NOH}-2}(MU-Cl)]2 ()
      with the appropriate neutral ligand or with [PPN]Cl, respectively. The cationic
      complexes are obtained in the presence of NaClO4. The reaction of with K(t)BuO
      affords the dinuclear oximato complex [Pd{MU-C,N,O-C6H4{C(NH2)[double bond,
      length as m-dash]NO}-2}(PTol3)]2 () or, in the presence of ClCH2py.HCl, the
      pincer derivative [Pd{C,N,N'-C6H4{C(NH2)[double bond, length as m
      dash]NOCH2(C5H4N-2)}-2}(PTol3)]ClO4 (). Complex reacts with XyNC to give the
      iminobenzoyl complex [Pd{C,N-C(N[double bond, length as m
      dash]Xy)C6H4{C(NH2)[double bond, length as m-dash]NOH}-2}Cl(CNXy)] () resulting
      from the insertion of XyNC into the Pd-C bond. The dinuclear complex
      [{Pd(tbbpy)}2{C,N,N',O-C6H4{C(NH)[double bond, length as m-dash]NO}-2}]ClO4 ()
      bearing a bridging tetradentate benzimido(oximate) ligand is obtained by reacting
      Pd(OAc)2 with tbbpy and the metal-ligand complex . The crystal structures of
      complexes , , and have been determined. 

PMID- 24129963
TI  - Osteopontin has a crucial role in osteoclast-like multinucleated giant cell
      formation.
AB  - The osteoclast (OC) is a major player in the pathogenic bone destruction of
      inflammatory bone diseases such as rheumatoid arthritis and Langerhans cell
      histiocytosis. Recently, it was shown that immature dendritic cells (iDC) fuse
      faster and more efficiently than monocytes in forming OC-like multinucleated
      giant cells (MGCs), and that osteopontin (OPN) is involved in the pathogenesis of
      inflammatory bone diseases. In this study, we hypothesized that OPN is a key
      factor for generation of OC-like MGCs from iDCs. We used an in vitro culture
      system to differentiate iDCs, derived from monocytes obtained from the blood of
      healthy donors, into OC-like MGCs. We evaluated OPN levels and expression of OPN
      receptors during the course of differentiation. OPN has an arginine-glycine
      aspartic acid (RGD) motif, and protease cleavage reveals a SVVYGLR motif. The
      concentrations of both full-length and cleaved forms of OPN increased during the
      course of OC-like MGC formation. Expression of OPN RGD- and SVVYGLR-recognizing
      receptors also increased at later stages. We analyzed whether blocking OPN
      binding to its receptors affected OC-like MGC formation. Monocytes treated with
      OPN siRNA were able to differentiate into iDCs effectively; however,
      differentiation of these iDCs into OC-like MGCs was significantly reduced. The
      formation of OC-like MGCs was not significantly reduced by RGD synthetic peptide.
      By contrast, SVVYGLR synthetic peptide caused a significant reduction. These data
      suggest that the cleaved form of OPN plays a critical role in driving iDC
      differentiation into OC-like MGCs in the early phase of differentiation, in an
      autocrine and/or paracrine fashion.

PMID- 24129964
TI  - Is pressure stressful? The impact of pressure on the stress response and category
      learning.
AB  - We examined the basic question of whether pressure is stressful. We proposed that
      when examining the role of stress or pressure in cognitive performance, it is
      important to consider the type of pressure, the stress response, and the aspect
      of cognition assessed. In Experiment 1, outcome pressure was not experienced as
      stressful but did lead to impaired performance on a rule-based (RB) category
      learning task, but not on a more procedural information-integration (II) task. In
      Experiment 2, the addition of monitoring pressure resulted in a modest stress
      response to combined pressure and impairment on both tasks. Across experiments,
      higher stress appraisals were associated with decreased performance on the RB,
      but not on the II, task. In turn, higher stress reactivity (i.e., heart rate) was
      associated with enhanced performance on the II, but not on the RB, task. This
      work represents an initial step toward integrating the stress cognition and
      pressure cognition literatures and suggests that integrating these fields may
      require consideration of the type of pressure, the stress response, and the
      cognitive system mediating performance. 

PMID- 24129965
TI  - Daikenchuto, a traditional Japanese herbal medicine, for the maintenance of
      surgically induced remission in patients with Crohn's disease: a retrospective
      analysis of 258 patients.
AB  - PURPOSE: Despite numerous studies, the best postoperative therapy for Crohn's
      disease is still undefined. We retrospectively evaluated the effects of
      postoperative maintenance therapy with daikenchuto, a traditional Japanese Kampo
      medicine, on the reoperation rate at 3 years in patients with Crohn's disease.
      METHODS: A total of 258 patients who underwent surgery for Crohn's disease were
      identified for the study. For the prevention of postoperative recurrence,
      patients were stratified to receive 5-aminosalicylic acid, azathioprine or
      daikenchuto, and their effects on preventing reoperation at 3 years were
      evaluated. RESULTS: Of the 258 patients, 44 required reoperation with intestinal
      resection within 3 years due to disease recurrence. The 3-year reoperation rate
      was significantly lower in the postoperative daikenchuto group than in the non
      daikenchuto group (11.3 vs. 24.5 %, P = 0.01), and was similarly significantly
      lower in the postoperative 5-aminosalicylic acid group than in the non-5
      aminosalicylic acid group (14.8 vs. 29.6 %, P = 0.0049). A multivariate Cox
      analysis showed that postoperative daikenchuto (P = 0.035) and postoperative 5
      aminosalicylic acid (P = 0.022) were significantly and independently associated
      with the rate of reoperation at 3 years in patients with Crohn's disease.
      CONCLUSION: We propose that continuous daikenchuto therapy is a clinically useful
      and feasible maintenance therapy for the prevention of postoperative reoperation
      in patients with Crohn's disease.

PMID- 24129967
TI  - Web Exclusives. The consult guys: green urine?!?

PMID- 24129966
TI  - Bitter melon extracts enhance the activity of chemotherapeutic agents through the
      modulation of multiple drug resistance.
AB  - Recently, we demonstrated that extracts of bitter melon (BME) can be used as a
      preventive/therapeutic agent in colon cancers. Here, we determined BME effects on
      anticancer activity and bioavailability of doxorubicin (DOX) in colon cancer
      cells. BME enhanced the effect of DOX on cell proliferation and sensitized the
      cells toward DOX upon pretreatment. Furthermore, there was both increased drug
      uptake and reduced drug efflux. We also observed a reduction in the expression of
      multidrug resistance conferring proteins (MDRCP) P-glycoprotein, MRP-2, and BCRP.
      Further BME suppressed DOX efflux in MDCK cells overexpressing the three efflux
      proteins individually, suggesting that BME is a potent inhibitor of MDR function.
      Next, we determined the effect of BME on PXR, a xenobiotic sensing nuclear
      receptor and a transcription factor that controls the expression of the three MDR
      genes. BME suppressed PXR promoter activity thereby suppressing its expression.
      Finally, we determined the effect of AMPK pathway on drug efflux because we have
      previously demonstrated that BME affects the pathway. However, inhibiting AMPK
      did not affect drug resistance, suggesting that BME may use different pathways
      for the anticancer and MDR modulating activities. Together, these results suggest
      that BME can enhance the bioavailability and efficacy of conventional
      chemotherapy.

PMID- 24129969
TI  - Patient and parental self-reports of executive functioning in a sample of young
      female adolescents with anorexia nervosa before and after cognitive remediation
      therapy.
AB  - OBJECTIVE: Previous studies assessing the potency of cognitive remediation
      therapy (CRT) have largely focused on performance-based assessments and how these
      change during the course of the intervention. Little is known of behavioural
      manifestations of such changes, and no previous studies have studied parental
      reports before and after CRT. METHOD: Patient and parental self-reports of
      executive function using the Behaviour Rating Inventory of Executive Function
      (BRIEF) were obtained for 17 adolescent patients in treatment for anorexia
      nervosa before and after CRT. RESULTS: Results indicated that patients scored
      significantly lower on the BRIEF shift subscale after CRT, whereas parental
      reports revealed significantly lower scores on the shift and emotional control
      subscales, and on the two composite indices Behavioural Regulation Index and
      Global Executive Composite. Case-wise comparisons support variations in executive
      functions in adolescents with anorexia nervosa. DISCUSSION: Changes are evaluated
      in light of the relationship between patients and parents and with regard to the
      limitations of the study design.

PMID- 24129968
TI  - [Osteochondroma and multiple osteochondromas: recommendations on the diagnostics
      and follow-up with special consideration to the occurrence of secondary
      chondrosarcoma].
AB  - PURPOSE: Osteochondroma represents the most common form of benign bone tumor.
      Clinical manifestations include deformity of bone, compression of surrounding
      tissue and vascular or neurological compromise. Osteochondromas may be solitary
      (solitary osteochondroma, SO) or multiple (multiple osteochondromas MO).
      Recurrence after surgery is a known problem especially in MO and malignant
      transformation is rare but more common in MO than in solitary cases. Reliable
      recommendations regarding diagnostics and clinical follow-up are currently
      lacking. PATIENTS AND METHODS: A comprehensive literature review and a review of
      own patient files with SO/MO treated between 2000 and 2011 in this hospital were
      performed. The age of patients at diagnosis, tumor localization, clinical
      aspects, recurrence and the risk of malignant transformation in secondary (i.e.
      epiexostotic) chondrosarcoma were analyzed. The follow-up including patients who
      received surgery ranged between 2 and 127 months for patients with SO and between
      2 and 84 months for MO. RESULTS: A total of 39 patients with SO from this
      hospital were included in the study. Out of 36 patients who received surgery 3
      recurrences were registered after an average time of 62 months. In addition, 11
      patients with MO were identified and all received surgery. In 5 out of 11 cases
      recurrences occurred after an average time of 20.6 months. Secondary
      chondrosarcomas were not recorded in this series. According to the literature an
      increased risk of malignant transformation was found for osteochondromas of the
      axial skeleton, in the proximal aspect of the extremities, as well as for
      recurrent tumors and for MO. Pain and/or increase in size of lesions after
      skeletal maturation were the most common clinical signs of transformation. There
      was a wide time interval between the initial diagnosis and the development of
      secondary chondrosarcoma. In MO secondary chondrosarcoma has been described
      before skeletal maturity. CONCLUSIONS: The risk of malignant transformation of SO
      is generally low. Axial lesions as well as recurrent osteochondromas and MO seem
      to have an increased risk of malignant transformation. The follow-up, requiring
      sufficient primary diagnostics, includes regular self-control and can usually be
      clinically carried out in more peripherally located lesions but in certain cases
      supplementary X-ray imaging is needed. In cases of anatomical regions which are
      more difficult to access manually, follow-up examination by magnetic resonance
      imaging (MRI) is the method of choice. Especially MO patients seem to benefit
      from long-term follow-up: when the tumor is located in the trunk and in
      (proximal) long bones MRI or whole-body MRI, respectively, should be performed
      once a year after skeletal maturity because of the higher risk of malignant
      transformation in these patients.

PMID- 24129970
TI  - Highly active, low-valence molybdenum- and tungsten-amide catalysts for
      bifunctional imine-hydrogenation reactions.
AB  - The reactions of [M(NO)(CO)4(ClAlCl3)] (M=Mo, W) with (iPr2PCH2CH2)2NH, (PN(H)P)
      at 90  degrees C afforded [M(NO)(CO)(PN(H)P)Cl] complexes (M=Mo, 1a; W, 1b). The
      treatment of compound 1a with KOtBu as a base at room temperature yielded the
      alkoxide complex [Mo(NO)(CO)(PN(H)P)(OtBu)] (2a). In contrast, with the amide
      base Na[N(SiMe3 )2 ], the PN(H) P ligand moieties in compounds 1a and 1b could be
      deprotonated at room temperature, thereby inducing dehydrochlorination into amido
      complexes [M(NO)(CO)(PNP)] (M=Mo, 3a; W, 3b; PNP=(iPr2PCH2CH2)2N)). Compounds 3a
      and 3b have pseudo-trigonal-bipyramidal geometries, in which the amido nitrogen
      atom is in the equatorial plane. At room temperature, compounds 3a and 3b were
      capable of adding dihydrogen, with heterolytic splitting, thereby forming pairs
      of isomeric amine-hydride complexes [Mo(NO)(CO)H(PN(H)P)] (4a(cis) and 4a(trans))
      and [W(NO)(CO)H(PN(H)P)] (4b(cis) and 4b(trans); cis and trans correspond to the
      position of the H and NO groups). H2 approaches the Mo/W=N bond in compounds 3a,b
      from either the CO-ligand side or from the NO-ligand side. Compounds 4a(cis) and
      4a(trans) were only found to be stable under a H2 atmosphere and could not be
      isolated. At 140  degrees C and 60 bar H2 , compounds 3a and 3b catalyzed the
      hydrogenation of imines, thereby showing maximum turnover frequencies (TOFs) of
      2912 and 1120 h(-1), respectively, for the hydrogenation of N-(4
      methoxybenzylidene)aniline. A Hammett plot for various para-substituted imines
      revealed linear correlations with a negative slope of -3.69 for para substitution
      on the benzylidene side and a positive slope of 0.68 for para substitution on the
      aniline side. Kinetics analysis revealed the initial rate of the hydrogenation
      reactions to be first order in c(cat.) and zeroth order in c(imine). Deuterium
      kinetic isotope effect (DKIE) experiments furnished a low kH /kD value (1.28),
      which supported a Noyori-type metal-ligand bifunctional mechanism with H2
      addition as the rate-limiting step.

PMID- 24129971
TI  - MRI manifestations of liver epithelioid and nonepithelioid angiomyolipoma.
AB  - PURPOSE: To retrospectively analyze the magnetic resonance imaging (MRI)
      manifestations of liver AML and compare the MRI manifestations of epithelioid and
      nonepithelioid angiomyolipoma (AML). MATERIALS AND METHODS: The study comprised a
      retrospective analysis of 11 patients whose hepatic AML was confirmed by surgical
      pathology. Routine MRI examination was performed in 11 patients, of which five
      were cases of epithelioid AML and six were cases of nonepithelioid AML. One case
      of nonepithelioid AML underwent a plain MRI scan only, while the remaining 10
      patients underwent MRI and dynamic contrast-enhanced scans. RESULTS: Chemical
      shift imaging detected more fat component cases than frequency the saturation
      method did (7/11 vs. 3/11). The difference was not statistically significant,
      however (P = 0.236). The degree of fatty component was different between
      epithelioid and nonepithelioid AML, but there was no significant difference
      between them (P = 0.766). Of the 10 cases in which enhancement scans were
      performed, nine had hyperenhancement in the arterial phase, and nine had capsule
      enhancement on delayed phase. CONCLUSION: The amount of fat content is not
      related to whether the tumor is epithelioid or nonepithelioid. Under dynamic
      contrast-enhancement MRI, epithelioid AML shows enhancement patterns similar to
      those of classic AML rich in vascular smooth muscles.

PMID- 24129972
TI  - Strong quantum confinement effects in kesterite Cu2ZnSnS4 nanospheres for organic
      optoelectronic cells.
AB  - X-ray photoelectron spectra, X-ray diffraction patterns, scanning electron
      microscopy images, and high-resolution transmission electron microscopy images
      showed that the as-prepared samples were Cu2ZnSnS4 (CZTS) nanospheres with a
      kesterite phase. Ultraviolet-visible absorption spectra for the CZTS nanospheres
      with an average crystallite size of 3.26 nm showed that the absorption edge
      corresponding to the energy gap shifted to the higher energy side due to the
      quantum confinement within the CZTS nanoparticles. Current-density measurements
      showed that the power conversion efficiency (0.952%) of the organic photovoltaic
      cells with CZTS nanospheres was much higher than that (0.120%) of the cells
      without CZTS nanospheres. 

PMID- 24129973
TI  - Natural history of left ventricular ejection fraction in patients with heart
      failure.
AB  - BACKGROUND: Patients with heart failure (HF) are typically designated as having
      reduced or preserved ejection fraction (HFREF, HFPEF) because of the importance
      of left ventricular ejection fraction (LVEF) on therapeutic decisions and
      prognosis. Such designations are not necessarily static, yet few data exist to
      describe the natural history of LVEF over time. METHODS AND RESULTS: We
      identified 2413 patients from Kaiser Permanente Colorado with a primary discharge
      diagnosis of HF between January 1, 2001, and December 31, 2008, who had >=2 LVEF
      measurements separated by >=30 days. We used multi-state Markov modeling to
      examine transitions among HFREF, HFPEF, and death. We observed a total of 8183
      transitions. Women were more likely than men to transition from HFREF to HFPEF
      (hazard ratio, 1.85; 95% confidence interval, 1.38-2.47). Patients who were
      adherent to beta-blockers were more likely to transition from HFREF to HFPEF
      (hazard ratio, 1.53; 95% confidence interval, 1.10-2.13) compared with patients
      who were nonadherent to beta-blockers, whereas angiotensin-converting enzyme or
      angiotensin II receptor blocker adherence was not associated with LVEF
      transitions. Patients who had a previous myocardial infarction were more likely
      to transition from HFPEF to HFREF (hazard ratio, 1.75; 95% confidence interval,
      1.26-2.42). CONCLUSIONS: In this cohort of patients with HF, LVEF is a dynamic
      factor related to sex, coexisting conditions, and drug therapy. These findings
      have implications for left ventricular systolic function ascertainment in
      patients with HF and support evidence-based therapy use, especially beta
      blockers.

PMID- 24129974
TI  - Treatment of older patients with HER2-positive metastatic breast cancer with
      pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized,
      double-blind, placebo-controlled phase III trial (CLEOPATRA).
AB  - Although the incidence of cancer increases with age, older patients are under
      represented in cancer treatment trials, resulting in limited data availability in
      this patient population. Here we present results from pre-defined subgroup
      analyses conducted by age group (<65 vs >= 65 years) from a randomized, double
      blind, placebo-controlled phase III trial in patients with HER2-positive
      metastatic breast cancer. Patients who had not received previous chemotherapy or
      biological therapy for HER2-positive locally recurrent, unresectable or
      metastatic breast cancer were randomly assigned to treatment with placebo,
      trastuzumab, and docetaxel or with pertuzumab, trastuzumab, and docetaxel.
      Primary endpoint was independently assessed progression-free survival. We
      performed pre-specified subgroup analyses of progression-free survival according
      to age. The study is registered with ClinicalTrials.gov, NCT00567190. 808
      patients were enrolled. Of those, 127 patients were 65 years of age or older
      (placebo arm: 67, pertuzumab arm: 60). Patients in both age groups experienced
      progression-free survival benefit with treatment in the pertuzumab arm (<65
      years: HR: 0.65; 95 % CI 0.53-0.80; >=65 years: HR: 0.52; 95 % CI 0.31-0.86).
      Diarrhoea, fatigue, asthenia, decreased appetite, vomiting, and dysgeusia were
      reported more frequently in patients 65 years of age or older compared with
      younger patients. Neutropenia and febrile neutropenia were reported less
      frequently in the older age group. The efficacy and safety data reported in
      CLEOPATRA suggest that the combined use of pertuzumab, trastuzumab, and docetaxel
      should not be limited by patient age.

PMID- 24129976
TI  - Preference weights for chemotherapy side effects from the perspective of women
      with breast cancer.
AB  - Perceptions among women with breast cancer about the relative importance of
      different potential chemotherapy side effects is not well understood. A survey
      was performed by women receiving chemotherapy for breast cancer. Grade I/II (mild
      to moderate) and III/IV (moderate to severe) descriptions of nine common
      chemotherapy side effects were assigned preference weights using the standard
      gamble technique. For each hypothetical side effect, patients could choose to
      stay in the respective side effect state or take a gamble between full health
      (probability p) or being dead (1 - p). For each side effect, p was varied until
      the patient was indifferent between these options. The survey also included
      questions about the importance of survival, slowing cancer growth, and quality of
      life. This analysis included 69 patients; mean age 54 years (range 35-84),
      representing all cancer stages. Standard gamble preferences were lowest (i.e.,
      least preferred) for grade III/IV nausea/vomiting (0.621), indicating that
      patients would, on average, risk a 38 % chance of being dead to avoid having
      grade III/IV nausea/vomiting for the rest of their lives. The next least
      preferred side effects were grade III/IV diarrhea (0.677) and grade III/IV
      sensory neuropathy (0.694). Survival appeared more important than slowing cancer
      growth and maintaining quality of life across cancer stages. Nevertheless,
      patients with advanced disease placed less importance on survival (p = 0.09) and
      higher importance on quality of life (p = 0.05). These standard gamble utilities
      provide unique insights into chemotherapy toxicities from the patient
      perspective. Differences in the relative importance of overall survival and
      quality of life with treatment existed between patients with different stages of
      disease. These studies should be expanded as the data may also be used to
      calculate quality-adjusted life expectancy in cost-effectiveness evaluations of
      breast cancer chemotherapies.

PMID- 24129975
TI  - MicroRNA signatures in hereditary breast cancer.
AB  - This study aims to identify signatures of miR associated with hereditary, BRCA1
      or BRCA2 mutation positive breast cancer (BC), and non-hereditary BC, either
      sporadic (SBC) or non-informative (BRCAX). Moreover, we search for signatures
      associated with tumor stage, immunohistochemistry and tumor molecular profile.
      Twenty formalin fixed paraffin embedded (FFPE) BCs, BRCA1, BRCA2, BRCAX and SBC,
      five per group were studied. Affymetrix platform miRNA v.3.0 was used to perform
      miR expression analysis. ER, PR, HER2 and Ki67 protein expression was analyzed by
      immunohistochemistry. BRCA1, BRCA2 and RASSF1 methylation analysis, AURKA copy
      number variations, and BRCA1 and BRCA2 deletions, were studied by MLPA. We
      validated eight of the miR selected by the arrays in 77 BCs by qRT-PCR. The miR
      profiles associated with tumor features were studied applying the Sparse Partial
      Least Squares Discriminant Analysis. MiR discrimination capability to distinguish
      hereditary and non-hereditary BC was analyzed by the discriminant function. With
      15 out of 1,733 hsa-miRs, it was possible to differentiate the four groups.
      BRCA1, BRCA2 and SBC were associated with clusters of hyper-expressed miRs, and
      BRCAX with hypo-expressed miRs. Hsa-miR-4417 and hsa-miR-423-3p expressions
      (included among the eight validated miRs) differentiated 70.1 % of hereditary and
      non-hereditary BCs. We found miR profiles associated with tumor features like
      node involvement, histological grade, ER, PR and HER2 expression. Regarding
      molecular parameters, we only found a weak association of miRs in BC harboring
      losses in AURKA. We conclude that array miR expression profiles can differentiate
      the four study groups using FFPE BC. However, miRs expression estimated by qRT
      PCR differentiates only hereditary and non-inherited BCs. The miR expression
      array is a simple and rapid approach that could be useful to facilitate the
      identification of those SBC carrying genetic or epigenetic changes in BRCA genes
      responsible of BRCA-like phenotype. These patients could benefit from the
      treatment with PARP inhibitors.

PMID- 24129977
TI  - New endeavors in gold catalysis--size matters.

PMID- 24129978
TI  - Special issue: Traditional foods: from culture, ecology and diversity, to human
      health and potential for exploitation.

PMID- 24129979
TI  - Site-dependent biological activity of valinomycin analogs bearing derivatizable
      hydroxyl sites.
AB  - Valinomycin (VLM, 1) is a K(+) ionophore cyclodepsipeptide capable of
      depolarizing mitochondria and inducing apoptosis to several mammalian cell types,
      including a number of tumor cell lines. With the aim of creating VLM-based ligand
      targeted anticancer drugs that may selectively convey VLM to pathological cells,
      we have previously introduced derivatizable hydroxyl handles into the VLM
      structure, allowing to access a three-entity library of monohydroxyl VLMs
      (HyVLMs) bearing the OH group at the isopropyl side chain of a D-Hyi, D-Val, or L
      Val residue (analogs 2-4, respectively). Herein, the levels of bioactivity
      retained by the conjugable HyVLMs have been assessed on the basis of their
      ability to alter the functionality of isolated rat-liver mitochondria.
      Experiments run with HyVLMs in the range 1-10 nM and in 20 or 125 mM KCl medium
      show that the hydroxyl group reduces the potency of HyVLMs relative to VLM to an
      extent that depends upon the molecular site involved in the hydroxylation. On the
      other hand, estimation of the stability constants of complexes (in methanol at 25
      degrees C) of each analog with Na(+), K(+), and Cs(+) reveals that HyVLMs nicely
      retain the VLM binding features, except for a moderate increase in the stability
      of Na(+) complexes. These findings, along with pertinent structural
      considerations, suggest that the incorporation of OH into the VLM structure might
      actually have altered its K(+) transporting ability across mitochondrial
      membranes. Besides facing new aspects of VLM structure-activity relationship,
      these studies set the basis for the rational design of ligand-HyVLMs conjugates
      through derivatization of hanging OH group.

PMID- 24129980
TI  - Aminooxy analog of histamine is an efficient inhibitor of mammalian L-histidine
      decarboxylase: combined in silico and experimental evidence.
AB  - Histamine plays highlighted roles in the development of many common, emergent and
      rare diseases. In mammals, histamine is formed by decarboxylation of L-histidine,
      which is catalyzed by pyridoxal-5'-phosphate (PLP) dependent histidine
      decarboxylase (HDC, EC 4.1.1.22). The limited availability and stability of the
      protein have delayed the characterization of its structure-function
      relationships. Our previous knowledge on mammalian HDC, derived from both in
      silico and experimental approaches, indicates that an effective competitive
      inhibitor should be capable to form an "external aldimine-like structure" and
      have an imidazole group, or its proper mimetic, which provides additional
      affinity of PLP-inhibitor adduct to the HDC active center. This is confirmed
      using HEK-293 cells transfected to express human HDC and the aminooxy analog of
      histidine, 4(5)-aminooxymethylimidazole (O-IMHA, IC50 ~ 2 * 10(-7) M) capable to
      form a PLP-inhibitor complex (oxime) in the enzyme active center. Taking
      advantage of the availability of the human HDC X-ray structure, we have also
      determined the potential interactions that could stabilize this oxime in the
      active site of mammalian HDC.

PMID- 24129981
TI  - Self-assembling synthesis of free-standing nanoporous graphene-transition-metal
      oxide flexible electrodes for high-performance lithium-ion batteries and
      supercapacitors.
AB  - The synthesis of nanoporous graphene by a convenient carbon nanofiber assisted
      self-assembly approach is reported. Porous structures with large pore volumes,
      high surface areas, and well-controlled pore sizes were achieved by employing
      spherical silica as hard templates with different diameters. Through a general
      wet-immersion method, transition-metal oxide (Fe3O4, Co3O4, NiO) nanocrystals can
      be easily loaded into nanoporous graphene papers to form three-dimensional
      flexible nanoarchitectures. When directly applied as electrodes in lithium-ion
      batteries and supercapacitors, the materials exhibited superior electrochemical
      performances, including an ultra-high specific capacity, an extended long cycle
      life, and a high rate capability. In particular, nanoporous Fe3O4-graphene
      composites can deliver a reversible specific capacity of 1427.5 mAh g(-1) at a
      high current density of 1000 mA g(-1) as anode materials in lithium-ion
      batteries. Furthermore, nanoporous Co3O4-graphene composites achieved a high
      supercapacitance of 424.2 F g(-1) . This work demonstrated that the as-developed
      freestanding nanoporous graphene papers could have significant potential for
      energy storage and conversion applications.

PMID- 24129982
TI  - Focal species of birds in European crops for higher tier pesticide risk
      assessment.
AB  - Focal species have been defined by the European Food Safety Authority (EFSA) as
      real species that represent others in a crop resulting from their potential
      higher level of exposure to pesticides. As such they are the most appropriate
      species for refining estimates of exposure further, through, for example, radio
      tracking and dietary studies. Plant protection product manufacturers collectively
      commissioned many studies in Europe, according to the EFSA guidelines, to
      identify focal species in different crops that may be used in risk assessments
      for spray applications of pesticides. Using frequency of occurrence in crops and
      risk-based criteria for exposure, all studies have been reviewed to identify if
      possible at least 1 focal species per feeding guild, per crop in the new
      registration zones for southern and central Europe. Some focal species repeatedly
      appeared across a wide range of arable or tree crops but not both, demonstrating
      broad adaptation to these 2 different crop structures. Many have widespread
      distributions, for example, 15 of the focal species have a distribution covering
      all agricultural regions of Europe (northern, central, and southern zones). Three
      species, corn bunting, serin, and tree sparrow, are restricted to the central and
      southern zones, whereas another 4 species, Sardinian and fan-tailed warbler, and
      crested and short-toed lark, are essentially restricted to the southern zone. The
      authors consider the focal species identified as suitable for risk assessment in
      Europe at the zonal level and for further refinement of exposure through studies,
      such as radio tracking or diet analysis, if necessary.

PMID- 24129983
TI  - Stress analysis in oral obturator prostheses over parallel and tilted implants:
      photoelastic imaging.
AB  - This study aimed to evaluate the stress distribution through the photoelastic
      method in implant-retained palatal obturators prostheses. Two photoelastic models
      with bucco-sinusal communication were fabricated, one model without implants and
      another with two parallel implants and one tilted in the molar region. A
      conventional obturator prosthesis and five implant-retained obturators dentures
      with different attachment systems were fabricated: OR, three individualized O
      rings; BC, bar clip; BOC, implants splinted by bars associated with two O-rings
      positioned at the center of the bar; OD, implants splinted by bars associated
      with two O-rings positioned in distal cantilever; and BOD, implants splinted by
      bars with clips associated with two O-rings positioned in distal cantilever. Each
      assembly (model/attachment system/prosthesis) was positioned in a circular
      polariscope and a load of 100 N was applied on each implant. The results were
      obtained by observing the photographic record of the tensions in the photoelastic
      models resulting from the application of load. It can be observed that a larger
      amount of stress fringes on BC system. It was concluded that the attachment
      system has a direct influence on the stress distribution of implant-retained
      obturator prostheses, with the three individualized O-rings exhibiting the lowest
      stress values, and tilted implants presented a biomechanical behavior similar to
      parallel implants.

PMID- 24129984
TI  - Discrimination of patients with diabetes mellitus and healthy subjects based on
      laser-induced breakdown spectroscopy of their fingernails.
AB  - Laser-induced breakdown spectroscopy (LIBS) is applied to investigate the effect
      of diabetes mellitus (DM) on the elemental composition of fingernails.
      Measurements are carried out on 85 fingernail clippings including 51 diabetic and
      34 control subjects. An auto-focus system has been designed and used in
      experiments to improve the repeatability of LIBS measurements. Classification of
      diabetic and nondiabetic subjects is examined using discriminant function
      analysis (DFA) method. This classification is based on 82 atomic, ionic, and
      molecular emission lines belonging to 13 elements as well as one molecule of
      fingernails. Emission lines that can be used as the best predictors are
      identified. The possibility of using this method for screening purposes is
      discussed based on the classification results. This preliminary work shows the
      ability of LIBS of fingernails in discrimination of DM patients and nondiabetic
      subjects using DFA method and its feasibility in screening purposes.

PMID- 24129985
TI  - [Echocardiography as primary diagnostic tool for valvular heart diseases].
AB  - Echocardiography is the method of choice for diagnostics and decision making in
      valvular heart diseases. It is a universally available diagnostic tool not
      limited by radiation exposure or toxicity of contrast agents. It is capable of
      displaying cardiac anatomy, function and blood flow allowing an integrative
      approach to diagnosing valvular heart diseases. Quantification of stenotic valve
      lesions by calculating the valve opening area is well established. On the other
      hand, quantification of valve regurgitation is more difficult as it relies on
      simplifications and assumptions on geometry of the regurgitation orifice and its
      boundaries. Three dimensional assessments of the regurgitation orifice and flow
      may improve the accuracy of grading of cardiac valve regurgitation. 

PMID- 24129986
TI  - [Imaging technique and current status of valvular heart disease using cardiac
      MRI].
AB  - The main indications for cardiac magnetic resonance imaging (MRI) in the
      evaluation of valvular heart disease are pathologies of the aortic and pulmonary
      valve. For mitral and tricuspid valve pathologies MRI is not the first line
      modality as these are usually well visualized by echocardiography. The advantages
      of MRI in valvular heart disease are a high reliability in the evaluation of
      ventricular volumes and function as well as the assessment of the perivalvular
      arterial or atrial structures. This reliability and the limitless access to any
      imaging plane partially compensates for the lower temporal and spatial resolution
      in comparison to echocardiography. In patients with congenital heart disease,
      cardiac MRI is established as a valuable diagnostic tool in daily clinical
      management, especially for the evaluation of pulmonary valve defects.
      Nevertheless, echocardiography remains the first-line diagnostic imaging tool for
      the foreseeable future. 

PMID- 24129987
TI  - [Imaging prior to transcatheter aortic valve implantation].
AB  - Percutaneous transcatheter aortic valve implantation (TAVI) is an established
      alternative to open heart surgery in patients with severe aortic stenosis (AS)
      unsuitable for conventional aortic valve replacement due to comorbidities with a
      high perioperative risk or contraindications. Preprocedural imaging plays a major
      role for adequate determination of indications and prosthesis selection,
      prosthesis sizing and therefore for a reduction of periprocedural complications.
      Besides Doppler echocardiography which is mainly used for grading of the severity
      of aortic valve stenosis and peri-interventional imaging, cardiac computed
      tomography (CCT) is the imaging modality of choice. The CCT procedure not only
      allows for reliably assessment and measuring of the complex 3-dimensional
      geometry of the aortic root but also for the aorta and the peripheral vessels
      used as potential access paths. 

PMID- 24129989
TI  - Change in performance in response to training load adjustment based on autonomic
      activity.
AB  - The primary aim of this study was to assess performance (Perf) changes in
      response to a new training strategy. Specifically, based on spectral analysis of
      heart rate variability (SA HRV) to determine autonomic nervous system (ANS)
      activity, training doses were adjusted to maintain vagal activity at a high and
      relatively stable level during training preparation. Trained athletes (5 male and
      5 female) aged 23.2+/-4.2 years voluntarily participated in the study. ANS
      activity was assessed during an orthoclinostatic test, and was represented by
      calculating HRV variables and a total score index. Over 17 weeks, improvement
      (1.4-8.5%) and deterioration (0.1-8.8%) in Perf were detected in 7 and 3
      athletes, respectively. A relationship (rs=0.684; P<0.05) between the change in
      Perf (DeltaPerf) and supine PHF during season was found. Supine HRV indices (PHF,
      PT, and MSSD) for the last 3 weeks of the HRV-adjusting period correlated
      (rs=0.636; 0.648; 0.648, P<0.05) with DeltaPerf. Based on the results, a high and
      relative stable vagal activity during preparation may indicate a readiness to
      train or appropriate recovery that positively affects Perf. In conclusion, daily
      quantification of ANS activity by SA HRV seems to be a promising tool for the
      enhancement of Perf. 

PMID- 24129990
TI  - Age affects exercise-induced improvements in heart rate response to exercise.
AB  - The aim of the present study was to analyze the effects of age on
      cardiorespiratory fitness (CRF), muscle strength and heart rate (HR) response to
      exercise adaptation in women in response to a long-term twice-weekly combined
      aerobic and resistance exercise program. 85 sedentary women, divided into young
      (YG; n=22, 30.3 +/- 6.2 years), early middle-aged (EMG; n=28, 44.1 +/- 2.5
      years), late middle-aged (LMG; n=20, 56.7 +/- 3.5 years) and older (OG; n=15,
      71.4 +/- 6.9 years) groups, had their CRF, muscle strength (1-repetition maximum
      test) and HR response to exercise (graded exercise test) measured before and
      after 12 months of combined exercise training. Exercise training improved CRF and
      muscle strength in all age groups (P<0.05), and no significant differences were
      observed between groups. Exercise training also improved resting HR and recovery
      HR in YG and EMG (P<0.05), but not in LMG and OG. Maximal HR did not change in
      any group. Combined aerobic and resistance training at a frequency of 2 days/week
      improves CRF and muscle strength throughout the lifespan. However, exercise
      induced improvements in the HR recovery response to exercise may be impaired in
      late middle-aged and older women.

PMID- 24129991
TI  - Small-sided game training improves aerobic capacity and technical skills in
      basketball players.
AB  - The aim of this study was to compare the effects of 2 training interventions
      based on small-sided games (SGG) and high-intensity interval training (HIT) on
      physical and technical performance of male junior basketball players. A secondary
      objective was to investigate if these effects were similar in starting and bench
      players. 18 players participated in a pre-testing session, 6-weeks intervention
      period and a post-testing session. Pre- and post-sessions involved assessments of
      aerobic fitness, repeated sprint ability (RSA), defensive and offensive agility,
      upper and lower body power, shooting and passing skills. Mixed-design analysis of
      variance (ANOVA) with Bonferroni corrected pairwise comparisons examined the
      effects of time and type of intervention on physical and technical performances.
      The main results showed that both interventions resulted in similar improvements
      in aerobic capacity (+3.4% vs. +4.1%), with greater improvements in bench players
      compared to starting players (+7.1% vs. +1.1%, P<0.05). However, RSA was
      unchanged after both interventions. In addition, compared to HIT, SSG resulted in
      greater improvements in defensive agility (+4.5% vs. -2.7%, P<0.05), shooting
      skills (+7.4% vs. -2.4%, P<0.05) and upper body power (+7.9% vs. -2.0%, P<0.05).
      These results suggest that SSG should be prioritized in physical conditioning of
      junior basketball players during the season. However, when RSA is targeted, more
      specific training seems necessary. 

PMID- 24129992
TI  - Abnormal signal intensities of the seminal vesicles in a screening population.
AB  - PURPOSE: To investigate the incidence of abnormal signal hyperintensity on T1
      weighted magnetic resonance imaging (MRI) of the seminal vesicles in a screening
      population in order to compare clinical indicators between subjects with and
      without signal abnormality. MATERIALS AND METHODS: Signal intensity of the
      seminal vesicles on T1-weighted images and clinical examinations were
      investigated in 3570 examinations of 1865 male subjects (mean age 54.8 years,
      range 23-86 years at the first examination). RESULTS: Abnormal signal
      hyperintensity was observed at least once in 32 subjects (1.7%). Subjects with
      the abnormality were significantly older (average age with and without the
      abnormality, 64.1 vs. 54.6, respectively, P < 0.001), and the incidence of
      abnormality increased with increasing age (0% for the age group <40, 0.3% for 40
      49, 1.3% for 50-59, 2.9% for 60-69, 5.9% for 70-79, and 10.1% for >80). No
      significant difference was found in clinical indicators except for serum
      creatinine (1.10 vs. 0.84 mg/dL, P < 0.001). Of 12 subjects with abnormal signal
      intensity and follow-up data, the finding persisted on the same side for at least
      11 months in seven subjects (58%). CONCLUSION: Abnormal signal intensity of the
      seminal vesicles was observed in 1.7% of screening population, and the imaging
      finding in isolation is unlikely to have clinical significance.

PMID- 24129994
TI  - Highly species-specific centromeric repetitive DNA sequences in lizards:
      molecular cytogenetic characterization of a novel family of satellite DNA
      sequences isolated from the water monitor lizard (Varanus salvator
      macromaculatus, Platynota).
AB  - Two novel repetitive DNA sequences, VSAREP1 and VSAREP2, were isolated from the
      water monitor lizard (Varanus salvator macromaculatus, Platynota) and
      characterized using molecular cytogenetics. The respective lengths and guanine
      cytosine (GC) contents of the sequences were 190 bp and 57.5% for VSAREP1 and 185
      bp and 59.7% for VSAREP2, and both elements were tandemly arrayed as satellite
      DNA in the genome. VSAREP1 and VSAREP2 were each located at the C-positive
      heterochromatin in the pericentromeric region of chromosome 2q, the centromeric
      region of chromosome 5, and 3 pairs of microchromosomes. This suggests that
      genomic compartmentalization between macro- and microchromosomes might not have
      occurred in the centromeric repetitive sequences of V. salvator macromaculatus.
      These 2 sequences did only hybridize to genomic DNA of V. salvator
      macromaculatus, but no signal was observed even for other squamate reptiles,
      including Varanus exanthematicus, which is a closely related species of V.
      salvator macromaculatus. These results suggest that these sequences were
      differentiated rapidly or were specifically amplified in the V. salvator
      macromaculatus genome.

PMID- 24129993
TI  - Patterns of population structure for inshore bottlenose dolphins along the
      eastern United States.
AB  - Globally distributed, the bottlenose dolphin (Tursiops truncatus) is found in a
      range of offshore and coastal habitats. Using 15 microsatellite loci and mtDNA
      control region sequences, we investigated patterns of genetic differentiation
      among putative populations along the eastern US shoreline (the Indian River
      Lagoon, Florida, and Charleston Harbor, South Carolina) (microsatellite analyses:
      n = 125, mtDNA analyses: n = 132). We further utilized the mtDNA to compare these
      populations with those from the Northwest Atlantic, Gulf of Mexico, and
      Caribbean. Results showed strong differentiation among inshore, alongshore, and
      offshore habitats (FST = 0.744). In addition, Bayesian clustering analyses
      revealed the presence of 2 genetic clusters (populations) within the 250 km
      Indian River Lagoon. Habitat heterogeneity is likely an important force
      diversifying bottlenose dolphin populations through its influence on social
      behavior and foraging strategy. We propose that the spatial pattern of genetic
      variation within the lagoon reflects both its steep longitudinal transition of
      climate and also its historical discontinuity and recent connection as part of
      Intracoastal Waterway development. These findings have important management
      implications as they emphasize the role of habitat and the consequence of its
      modification in shaping bottlenose dolphin population structure and highlight the
      possibility of multiple management units existing in discrete inshore habitats
      along the entire eastern US shoreline. 

PMID- 24130000
TI  - Ionic self-assembly provides dense arrays of individualized, aligned single
      walled carbon nanotubes.
AB  - Wrap and stack: Polyanionic [arylene]ethynylene polymers that helically wrap
      single-walled carbon nanotubes (SWNTs) enable the production of functionalized
      SWNTs that are soluble in organic solvents. These SWNTs can assemble into
      structures featuring aligned nanotubes that maintain the optoelectronic
      properties of individual SWNTs. 

PMID- 24130001
TI  - Passive and active defense in toads: the parotoid macroglands in Rhinella marina
      and Rhaebo guttatus.
AB  - Amphibians have many skin poison glands used in passive defense, in which the
      aggressor causes its own poisoning when biting prey. In some amphibians the skin
      glands accumulate in certain regions forming macroglands, such as the parotoids
      of toads. We have discovered that the toad Rhaebo guttatus is able to squirt jets
      of poison towards the aggressor, contradicting the typical amphibian defense. We
      studied the R. guttatus chemical defense, comparing it with Rhinella marina, a
      sympatric species showing typical toad passive defense. We found that only in R.
      guttatus the parotoid is adhered to the scapula and do not have a calcified
      dermal layer. In addition, in this species, the plugs obstructing the glandular
      ducts are more fragile when compared to R. marina. As a consequence, the manual
      pressure necessary to extract the poison from the parotoid is twice as high in R.
      marina when compared to that used in R. guttatus. Compared to R. marina, the
      poison of R. guttatus is less lethal, induces edema and provokes nociception four
      times more intense. We concluded that the ability of R. guttatus to voluntary
      squirt poison is directly related to its stereotyped defensive behavior, together
      with the peculiar morphological characteristics of its parotoids. Since R.
      guttatus poison is practically not lethal, it is possibly directed to predators'
      learning, causing disturbing effects such as pain and edema. The unique mechanism
      of defense of R. guttatus may mistakenly justify the popular myth that toads, in
      general, squirt poison into people's eyes.

PMID- 24130002
TI  - Chiral-Zn(NTf2)2-complex-catalyzed diastereo- and enantioselective direct
      conjugate addition of arylacetonitriles to alkylidene malonates.
AB  - Chiral N,N'-dioxide/Zn(NTf2)2 complexes were demonstrated to be highly effective
      in the direct asymmetric conjugate addition of arylacetonitriles to alkylidene
      malonates under mild conditions. A wide range of substrates were tolerated to
      afford their corresponding products in moderate-to-good yields with high
      diastereoselectivities (82:18->99:1 d.r.) and enantioselectivities (81-99% ee).
      The reactions performed well, owing to the high Lewis acidity of the metal
      triflimidate and a ligand-acceleration effect. The N,N'-dioxide also benefited
      the deprotonation process as a Bronsted base. The catalytic reaction could be
      performed on the gram-scale with retention of yield, diastereoselectivity, and
      enantioselectivity. The products that contained functional groups were ready for
      further manipulation. In addition, a possible catalytic model was proposed to
      explain the origin of the asymmetric induction.

PMID- 24130003
TI  - Comparable performance of the Kansas City Cardiomyopathy Questionnaire in
      patients with heart failure with preserved and reduced ejection fraction.
AB  - BACKGROUND: Despite the growing epidemic of heart failure with preserved ejection
      fraction (HFpEF), no valid measure of patients' health status (symptoms,
      function, and quality of life) exists. We evaluated the Kansas City
      Cardiomyopathy Questionnaire (KCCQ), a validated measure of HF with reduced EF,
      in patients with HFpEF. METHODS AND RESULTS: Using a prospective HF registry, we
      dichotomized patients into HF with reduced EF (EF<= 40) and HFpEF (EF>=50). The
      associations between New York Heart Association class, a commonly used criterion
      standard, and KCCQ Overall Summary and Total Symptom domains were evaluated using
      Spearman correlations and 2-way ANOVA with differences between patients with HF
      with reduced EF and HFpEF tested with interaction terms. Predictive validity of
      the KCCQ Overall Summary scores was assessed with Kaplan-Meier curves for death
      and all-cause hospitalization. Covariate adjustment was made using Cox
      proportional hazards models. Internal reliability was assessed with Cronbach's
      alpha. Among 849 patients, 200 (24%) had HFpEF. KCCQ summary scores were strongly
      associated with New York Heart Association class in both patients with HFpEF (r=
      0.62; P<0.001) and HF with reduced EF (r=-0.55; P=0.27 for interaction). One-year
      event-free rates by KCCQ category among patients with HFpEF were 0 to 25=13.8%,
      26 to 50=59.1%, 51 to 75=73.8%, and 76 to 100=77.8% (log rank P<0.001), with no
      significant interaction by EF (P=0.37). The KCCQ domains demonstrated high
      internal consistency among patients with HFpEF (Cronbach's alpha=0.96 for overall
      summary and >=0.69 in all subdomains). CONCLUSIONS: Among patients with HFpEF,
      the KCCQ seems to be a valid and reliable measure of health status and offers
      excellent prognostic ability. Future studies should extend and replicate our
      findings, including the establishment of its responsiveness to clinical change.

PMID- 24130004
TI  - Practice-level variation in use of recommended medications among outpatients with
      heart failure: Insights from the NCDR PINNACLE program.
AB  - BACKGROUND: The objective of this study is to examine practice-level variation in
      rates of guideline-recommended treatment for outpatients with heart failure and
      reduced ejection fraction, and to examine the association between treatment
      variation and practice site, independent of patient factors. METHODS AND RESULTS:
      Cardiology practices participating in the National Cardiovascular Disease
      Registry Practice Innovation and Clinical Excellence registry from July 2008 to
      December 2010 were evaluated. Practice rates of treatment with angiotensin
      converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers and
      an optimal combined treatment measure were determined for patients with heart
      failure and reduced ejection fraction and no documented contraindications.
      Multivariable hierarchical regression models were adjusted for demographics,
      insurance status, and comorbidities. A median rate ratio was calculated for each
      therapy, which describes the likelihood that the treatment of a patient with
      given comorbidities would differ at 2 randomly selected practices. We identified
      12 556 patients from 45 practices. The unadjusted practice-level prescription
      rates ranged from 44% to 100% for angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers (median, 85%; interquartile range, 75%
      89%), from 49% to 100% for beta-blockers (median, 92%; interquartile range, 83%
      95%), and from 37% to 100% for optimal combined treatment (median, 79%;
      interquartile range, 66%-85%). The adjusted median rate ratio was 1.11 (95%
      confidence interval, 1.08-1.18) for angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers therapy, 1.08 (95% confidence interval,
      1.05-1.15) for beta-blockers therapy, and 1.17 (1.13-1.26) for optimal combined
      treatment. CONCLUSIONS: Variation in the use of guideline-recommended medications
      for patients with heart failure and reduced ejection fraction exists in the
      outpatient setting. Addressing practice-level differences may be an important
      component of improving quality of care for patients with heart failure and
      reduced ejection fraction.

PMID- 24130006
TI  - Photoelectrochemical hydrogen production on alpha-Fe2O3 (0001): insights from
      theory and experiments.
AB  - The photoelectrochemical (PEC) decomposition of organic compounds in wastewater
      is investigated by using quantum chemical (DFT) methods to evaluate alternatives
      to water splitting for the production of renewable and sustainable hydrogen.
      Methanol is used as a model organic species for the theoretical evaluations of
      electrolysis on the surface of the widely available semiconductor hematite, alpha
      Fe2 O3 , a widely studied photocatalyst. Three different alpha-Fe2 O3 surface
      terminations were investigated, including the predominant surface found in
      aqueous electrolytes, (OH)3 R. The PEC oxidation of methanol is energetically
      downhill, producing CO2 and protons. The protons are reduced to hydrogen on the
      cathode. Experimental PEC measurements were also performed for several
      polyalcoholic compounds, glycerol, erythritol, and xylitol, on alpha-Fe2 O3 as
      the photocatalyst and showed high incident-photon-to-current-efficiencies (IPCE)
      that were much greater than those of water splitting. Interestingly, high IPCEs
      were observed for hydrogen production from polyalcohols in the absence of any
      applied bias, which was not thought to be possible on hematite. These results
      support the potential application of PEC for hydrogen production by using widely
      available hematite for the PEC oxidation of selected components of organic
      wastewater present in large quantities from anthropogenic and industrial sources.

PMID- 24130007
TI  - Effect of suspended uncontaminated sediment on persistent organic pollutant
      release.
AB  - The transport and fate of persistent organic pollutants (POPs) during
      resuspension events were investigated using a batch mixing technique. This
      technique allowed for the determination of sorption and desorption kinetics under
      more realistic mixing conditions than those used in previous investigations. It
      was demonstrated that sorption follows second-order kinetics that are dependent
      on both POP concentration and the total suspended solids (TSS) of the system.
      Desorption shows a similar dependence. To further characterize pollutant release,
      the impact on maximum POP release of suspending uncontaminated sediment
      concomitantly with contaminated sediment was investigated, as this more
      accurately models real-world resuspension events. It was found that even
      relatively low ratios of uncontaminated to contaminated sediment (1:2) yield a
      maximum POP release nearly 10 times lower than for systems containing only
      contaminated sediment. Increasing the ratio of uncontaminated sediment further
      reduced maximum POP release. These results highlight an important limitation of
      laboratory desorption experiments and current risk-assessment models related to
      dredging operations; under typical field conditions, the impact of dredging on
      pollutant transport and fate may be greatly overpredicted.

PMID- 24130005
TI  - Cardiovascular effects of 1 year of alagebrium and endurance exercise training in
      healthy older individuals.
AB  - BACKGROUND: Lifelong exercise training maintains a youthful compliance of the
      left ventricle (LV), whereas a year of exercise training started later in life
      fails to reverse LV stiffening, possibly because of accumulation of irreversible
      advanced glycation end products. Alagebrium breaks advanced glycation end product
      crosslinks and improves LV stiffness in aged animals. However, it is unclear
      whether a strategy of exercise combined with alagebrium would improve LV
      stiffness in sedentary older humans. METHODS AND RESULTS: Sixty-two healthy
      subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium
      (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right
      heart catheterization to define LV pressure-volume curves; secondary functional
      outcomes included cardiopulmonary exercise testing and arterial compliance. A
      total of 57 of 62 subjects (67 +/- 6 years; 37 f/20 m) completed 1 year of
      intervention followed by repeat measurements. Pulmonary capillary wedge pressure
      and LV end-diastolic volume were measured at baseline, during decreased and
      increased cardiac filling. LV stiffness was assessed by the slope of LV pressure
      volume curve. After intervention, LV mass and end-diastolic volume increased and
      exercise capacity improved (by ~8%) only in the exercise groups. Neither LV mass
      nor exercise capacity was affected by alagebrium. Exercise training had little
      impact on LV stiffness (training * time effect, P=0.46), whereas alagebrium
      showed a modest improvement in LV stiffness compared with placebo (medication *
      time effect, P=0.04). CONCLUSIONS: Alagebrium had no effect on hemodynamics, LV
      geometry, or exercise capacity in healthy, previously sedentary seniors. However,
      it did show a modestly favorable effect on age-associated LV stiffening. CLINICAL
      TRIAL REGISTRATION- URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01014572.

PMID- 24130008
TI  - Retrospective assessment of the utility of an iron-based agent for contrast
      enhanced magnetic resonance venography in patients with endstage renal diseases.
AB  - PURPOSE: To compare abdominopelvic and lower extremity venous enhancement in
      contrast-enhanced magnetic resonance venography (ceMRV), using iron-based
      ferumoxytol and gadolinium-based gadofosveset. MATERIALS AND METHODS: This was a
      Health Insurance Portability and Accountability Act (HIPAA)-compliant
      retrospective study. Thirty-four patients were identified who had undergone ceMRV
      using either ferumoxtyol (Group A, all with chronic renal insufficiency) or
      gadofosveset (Group B). Two radiologists rated confidence for evaluation of the
      major abdominopelvic and lower extremity veins from 4 (excellent confidence) to 1
      (nondiagnostic). A third radiologist measured signal intensity ratios (SIRs) of
      venous segments compared with adjacent muscles. Scores were compared using
      repeated-measures analysis of variance (ANOVA). The medical record was searched
      for contemporaneous imaging to confirm the ceMRV findings. RESULTS: In Group A,
      14/225 venous segments were thrombosed, compared with 18/282 in Group B. There
      was no statistically significant difference between confidence scores (3.79 +/-
      0.44 vs. 3.85 +/- 0.44, P = 0.34) or SIRs (2.40 +/- 0.73 vs. 2.38 +/- 0.51, P =
      0.51) for patent segments in the two groups, nor were confidences scores (3.89 +/
      0.29 vs. 3.72 +/- 0.46, P = 0.31) or SIRs (0.90 +/- 0.12 vs. 0.84 +/- 0.19, P =
      0.31) significantly different for thrombosed segments. Contemporaneous imaging
      confirmed ceMRV findings in 227 segments. CONCLUSION: ceMRV can be performed with
      ferumoxytol, yielding similar image quality to a blood pool gadolinium-based
      contrast agent.

PMID- 24130009
TI  - Shotgun-proteomics-based clinical testing for diagnosis and classification of
      amyloidosis.
AB  - Shotgun proteomics technology has matured in the research laboratories and is
      poised to enter clinical laboratories. However, the road to this transition is
      sprinkled with major technical unknowns such as long-term stability of the
      platform, reproducibility of the technology and clinical utility over traditional
      antibody-based platforms. Further, regulatory bodies that oversee the clinical
      laboratory operations are unfamiliar with this new technology. As a result,
      diagnostic laboratories have avoided using shotgun proteomics for routine
      diagnostics. In this perspectives article, we describe the clinical
      implementation of a shotgun proteomics assay for amyloid subtyping, with a
      special emphasis on standardizing the platform for better quality control and
      earning clinical acceptance. This assay is the first shotgun proteomics assay to
      receive regulatory approval for patient diagnosis. The blueprint of this assay
      can be utilized to develop novel proteomics assays for detecting numerous other
      disease pathologies.

PMID- 24130010
TI  - A rapid and highly specific method to evaluate the presence of pyrrolizidine
      alkaloids in Borago officinalis seed oil.
AB  - Pyrrolizidine alkaloids (PAs) are complex molecules, present in plants as free
      bases and N-oxides. They are known for their hepatotoxicity, and consequently
      there is a health risk associated with the use of medicinal herbs that contain
      PAs. Unfortunately, there is no international regulation of PAs in foods, unlike
      those for herbs and medicines: in particular, for herbal preparation or herbal
      extracts, the total PA content must not exceed 1 ug/kg or 1 ug/l, respectively.
      Borago officinalis seed oil is a source of gamma-linolenic acid, and its use is
      increased in both pharmaceutical and health food industries. Even if studies
      based on gas chromatography and TLC methods showed that PAs are not co-extracted
      with oil, the development of a rapid and sensitive method able to evaluate the
      presence of PAs in commercially available products is surely of interest. The
      presence of PAs in a commercially available Borago officinalis seed oil was
      tested either in the oil sample diluted with tetrahydrofuran/methanol (MeOH)/H2 O
      (85/10/5 v:v:v) or after extraction with MeOH/H2 O (50/50 v:v) solution The
      samples were analysed by electrospray ionization in positive ion mode and in high
      mass resolution (60,000) conditions. In both cases to evaluate the effectiveness
      of the method, spiking experiments were performed adding known amount of two PA
      standards to the borage seed oil. A limit of detection in the order of 200 ppt
      was determined for these two compounds, strongly analogous to Borago officinalis
      seed oil PAs. Consequently, if present, PAs level in Borago officinalis seed oil
      must lower than 200 ppt.

PMID- 24130011
TI  - Mapping the glycation sites in the neoglycoconjugate from hexasaccharide antigen
      of Vibrio cholerae, serotype Ogawa and the recombinant tetanus toxin C-fragment
      carrier.
AB  - We report herein the glycation sites in a vaccine candidate for cholera formed by
      conjugation of the synthetic hexasaccharide fragment of the O-specific
      polysaccharide of Vibrio cholerae, serotype Ogawa, to the recombinant tetanus
      toxin C-fragment (rTT-Hc) carrier. Matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry analysis of the vaccine revealed that it is
      composed of a mixture of neoglycoconjugates with carbohydrate : protein ratios of
      1.9 : 1, 3.0 : 1, 4.0 : 1, 4.9 : 1, 5.9 : 1, 6.9 : 1, 7.9 : 1 and 9.1 : 1. Liquid
      chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tryptic and
      GluC V8 digests allowed identification of 12 glycation sites in the carbohydrate
      protein neoglycoconjugate vaccine. The glycation sites are located exclusively on
      lysine (Lys) residues and are listed as follows: Lys 22, Lys 61, Lys 145, Lys
      239, Lys 278, Lys 318, Lys 331, Lys 353, Lys 378, Lys 389, Lys 396 and Lys 437.
      Based on the 3-D representation of the rTT-Hc protein, all the glycation sites
      correspond to lysines located at the outer surface of the protein.

PMID- 24130012
TI  - Investigating the presence of omeprazole in waters by liquid chromatography
      coupled to low and high resolution mass spectrometry: degradation experiments.
AB  - Omeprazole is one of the most consumed pharmaceuticals around the world. However,
      this compound is scarcely detected in urban wastewater and surface water. The
      absence of this pharmaceutical in the aquatic ecosystem might be due to its
      degradation in wastewater treatment plants, as well as in receiving water. In
      this work, different laboratory-controlled degradation experiments have been
      carried out on surface water in order to elucidate generated omeprazole
      transformation products (TPs). Surface water spiked with omeprazole was subjected
      to hydrolysis, photo-degradation under both sunlight and ultraviolet radiation
      and chlorination. Analyses by liquid chromatography coupled to quadrupole time-of
      flight mass spectrometry (LC-QTOF MS) permitted identification of up to 17
      omeprazole TPs. In a subsequent step, the TPs identified were sought in surface
      water and urban wastewater by LC-QTOF MS and by LC coupled to tandem mass
      spectrometry with triple quadrupole. The parent omeprazole was not detected in
      any of the samples, but four TPs were found in several water samples. The most
      frequently detected compound was OTP 5 (omeprazole sulfide), which might be a
      reasonable candidate to be included in monitoring programs rather than the parent
      omeprazole.

PMID- 24130013
TI  - N-alkylpyridinium quaternization for assisting electrospray ionization of sterols
      in oil by quadrupole-time of flight mass spectrometry.
AB  - RATIONALE: The illegal cooking oil has become a serious social problem and raised
      widespread alarm recently. However, an efficient and sensitive technique for
      identifying the potential illegal cooking oil is still unavailable, especially
      when mixed with the ordinary ones; there is an urgent need to develop an
      efficient method for identifying the illegal cooking oil. Sterols in the cooking
      oil could be used as an indicator to identify the source and quality of oil by
      detecting the kinds of phytosterols and zoosterols. However, those sterols are
      difficult to be ionized by electrospray ionization, which resulted in the low
      sensitivity in electrospray ionization (ESI)-mass spectrometric (MS) analysis.
      METHODS: N-alkylpyridinium isotope quaternization was extended to charge label
      sterols in different cooking oil and attached N-cationic pyridinium tag onto the
      sterols in the presence of trifluoromethanesulfonic anhydride (Tf2 O); the kinds
      of sterols were identified and quantified by comparing d0 /d5 pairs and product
      scan from ESI-quadrupole-time of flight (Q-TOF) MS analysis. RESULTS: The
      derivatized sterols were attached with permanent charge, resulting in the
      significant enhancement of ionization in ESI-Q-TOF MS analysis. The detection
      limits of analytes were improved to 0.02-0.05 ng/mL; different kinds of
      phytosterol, zoosterol and oxides were identified and quantified by comparing d0
      /d5 pairs from full scan and product scan. The method was applied in the
      detection of zoosterol for identifying the potential recycled cooking oil, even
      when the illegal oil has been blended into the ordinary one. More zoosterol was
      detected in the recycled oil compared with other cooking oil. CONCLUSIONS: The
      use of N-alkylpyridinium isotope quaternization method provided an alternative
      method for identifying the potential illegal cooking oil.

PMID- 24130014
TI  - Electrospray ionization mass spectrometry and partial least squares discriminant
      analysis applied to the quality control of olive oil.
AB  - Direct infusion electrospray ionization mass spectrometry in the positive ion
      mode [ESI(+)-MS] is used to obtain fingerprints of aqueous-methanolic extracts of
      two types of olive oils, extra virgin (EV) and ordinary (OR), as well as of
      samples of EV olive oil adulterated by the addition of OR olive oil and other
      edible oils: corn (CO), sunflower (SF), soybean (SO) and canola (CA). The MS data
      is treated by the partial least squares discriminant analysis (PLS-DA) protocol
      aiming at discriminating the above-mentioned classes formed by the genuine olive
      oils, EV (1) and OR (2), as well as the EV adulterated samples, i.e. EV/SO (3),
      EV/CO (4), EV/SF (5), EV/CA (6) and EV/OR (7). The PLS-DA model employed is built
      with 190 and 70 samples for the training and test sets, respectively. For all
      classes (1-7), EV and OR olive oils as well as the adulterated samples (in a
      proportion varying from 0.5 to 20.0% w/w) are properly classified. The developed
      methodology required no ions identification and demonstrated to be fast, as each
      measurement lasted about 3 min including the extraction step and MS analysis, and
      reliable, because high sensitivities (rate of true positives) and specificities
      (rate of true negatives) were achieved. Finally, it can be envisaged that this
      approach has potential to be applied in quality control of EV olive oils.

PMID- 24130015
TI  - Comparison of the sensitivity of mass spectrometry atmospheric pressure
      ionization techniques in the analysis of porphyrinoids.
AB  - The porphyrinoids chemistry is greatly dependent on the data obtained in mass
      spectrometry. For this reason, it is essential to determine the range of
      applicability of mass spectrometry ionization methods. In this study, the
      sensitivity of three different atmospheric pressure ionization techniques,
      electrospray ionization, atmospheric pressure chemical ionization and atmospheric
      pressure photoionization, was tested for several porphyrinods and their
      metallocomplexes. Electrospray ionization method was shown to be the best
      ionization technique because of its high sensitivity for derivatives of
      cyanocobalamin, free-base corroles and porphyrins. In the case of metallocorroles
      and metalloporphyrins, atmospheric pressure photoionization with dopant proved to
      be the most sensitive ionization method. It was also shown that for relatively
      acidic compounds, particularly for corroles, the negative ion mode provides
      better sensitivity than the positive ion mode. The results supply a lot of
      relevant information on the methodology of porphyrinoids analysis carried out by
      mass spectrometry. The information can be useful in designing future MS or liquid
      chromatography-MS experiments.

PMID- 24130016
TI  - Arm-length distribution in four-arm star-propoxylated ethylenediamine polyol by
      tandem mass spectrometry.

PMID- 24130018
TI  - [Challenges for the urology resident: focus urolithiasis].

PMID- 24130020
TI  - Chemical studies on Taxus canadensis.
AB  - A series of new taxanes, 1-93, have been isolated, together with 37 known taxoids
      including Taxol((r)) (paclitaxel) and cephalomannine, from the Canadian yew,
      Taxus canadensis (Taxaceae) in the past 30 years. These new taxoids possess
      various skeletons containing 5/7/6, 6/10/6, 6/5/5/6, 6/8/6, and 6/12 ring systems
      and six new taxanes with four novel skeletons, i.e., a taxane with a 6/6/8/6 ring
      system, a taxane with a [3.3.3] propellane skeleton, three taxanes with [3.3.3]
      [3.4.5] dipropellane sytems, as well as a novel taxane with a unique 5/5/4/6/6/6
      hexacyclic skeleton, containing a unique [3.3.2] propellane, were isolated for
      the first time from natural sources. It should be emphasized that 13-acetyl-9
      dihydrobaccatin III, a very useful starting material for the semisynthesis of
      Taxol((r)) and Taxotere((r)) , represents the most abundant taxane in the needles
      of this yew tree. These findings establish the above mentioned yew tree as
      significantly different from the remaining species. On the other hand, some
      chemical modifications on the taxanes isolated from this plant were carried out. 

PMID- 24130019
TI  - Dysregulation in lung immunity - the protective and pathologic Th17 response in
      infection.
AB  - Th17 cytokines can play both protective and pathologic roles in the airways. An
      emerging theme in Th17 cytokine biology is that these responses can mediate
      tissue pathology when downstream effector cells are dysfunctional, such as
      neutrophils lacking functional NADPH oxidase in the case of chronic granulomatous
      disease, or epithelial cells lacking appropriate ion transport as in the case of
      cystic fibrosis. In this Mini-Review we highlight recent advances in the
      protective and pathologic roles of Th17 cytokines in the context of infection at
      the pulmonary barrier. 

PMID- 24130021
TI  - Phytochemical and biological studies of Chloranthus medicinal plants.
AB  - The plants of genus Chloranthus have been investigated in many chemical and
      pharmacological laboratories due to their complex secondary metabolites and
      diverse bioactivities. The aim of this review is to provide an up-to-date
      overview on the chemistry and bioactivity of the compounds isolated, mainly
      sesquiterpenoids and diterpenoids, from the genus Chloranthus over the past few
      decades. 

PMID- 24130022
TI  - Phytochemistry of the carnivorous sundew genus Drosera (Droseraceae) - future
      perspectives and ethnopharmacological relevance.
AB  - Species of the carnivorous genus Drosera L. have long been a source of valuable
      natural products. The various phytochemicals characteristic of these species,
      particularly 1,4-naphthoquinones and flavonoids, have contributed to the diverse
      utilization of sundews in traditional medicine systems worldwide. A growing
      number of studies have sought to investigate the comparative phytochemistry of
      Drosera species for improved sources of pharmaceutically important compounds. The
      outcomes of these studies are here collated, with emergent trends discussed in
      detail. Important factors which affect production of secondary metabolites in
      plants are critically examined, such as environmental influences and in vitro
      culture, and recommendations subsequently presented based on this. Explicitly,
      the current review aims to i) present an updated, comprehensive listing of the
      phytochemical constituents of the genus (including quantitative data where
      available), ii) summarize important factors which may influence the production of
      phytopharmaceuticals in plants, and iii) recommend guidelines for future research
      based on the above, including improved standardization and quality control. We
      have also included a section discussing future perspectives of research on
      Drosera spp. based on three different research lines i) the potential to produce
      much needed lead compounds for treatment of tuberculosis, ii) the potential role
      of anthocyanins in nitrogen transport, and iii) research into 'Natural Deep
      Eutectic' solvents produced by Drosera spp. in the droplets or 'dew' employed to
      capture insect prey. 

PMID- 24130023
TI  - Radioprotectors - the evergreen topic.
AB  - To protect organisms from ionizing radiation (IR), and to reduce morbidity or
      mortality, various agents, called radioprotectors, have been utilized. Because
      radiation-induced cellular damage is attributed primarily to the harmful effects
      of free radicals, molecules with radical-scavenging properties are particularly
      promising as radioprotectors. Early development of such agents focused on thiol
      synthetic compounds, known as WR protectors, but only amifostine (WR-2721) has
      been used in clinical trials as an officially approved radioprotector. Besides
      thiol compounds, various compounds with different chemical structure were
      investigated, but an ideal radioprotector has not been found yet. Plants and
      natural products have been evaluated as promising sources of radioprotectors
      because of their low toxicity, although they exhibit an inferior protection level
      compared to synthetic thiol compounds. Active plant constituents seem to exert
      the radioprotection through antioxidant and free radical-scavenging activities.
      Our research established that plants containing polyphenolic compounds
      (raspberry, blueberry, strawberry, grape, etc.) exhibit antioxidative activities
      and protect genetic material from IR. 

PMID- 24130024
TI  - Synthesis and biological assays of 9-(acylamino) homocamptothecins as DNA
      topoisomerase I inhibitors.
AB  - In an effort to improve the stability of homocamptothecin and reduce the
      toxicity, novel homocamptothecin analogs with acylamino groups at C(9) were
      designed and synthesized. The cytotoxic activities of all the synthetic compounds
      against three cancer cell lines were evaluated by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and irinotecan was used as
      reference compound. Compound 7c with a piperidinylacetamido group and 10a with
      phenylacetamido group at C(9) showed potent activities both in vitro and in vivo.
      In addition, they also revealed remarkable topoisomerase I inhibitions which were
      exhibited with well-established bonds with amino acid residues Arg364 and Asp533
      in the active pocket. On the basis of the biological activities, 7c and 10a would
      be potential candidates for further studies. 

PMID- 24130025
TI  - Application of two-dimensional NMR spectroscopy to metabotyping laboratory
      Escherichia coli strains.
AB  - NMR Spectroscopy has been established as a major tool for identification and
      quantification of metabolites in a living system. Since the metabolomics era
      began, one-dimensional NMR spectroscopy has been intensively employed due to its
      simplicity and quickness. However, it has suffered from an inevitable overlap of
      signals, thus leading to inaccuracy in identification and quantification of
      metabolites. Two-dimensional (2D) NMR has emerged as a viable alternative because
      it can offer higher accuracy in a reasonable amount of time. We employed (1)
      H,(13) C-HSQC to profile metabolites of six different laboratory E. coli strains.
      We identified 18 metabolites and observed clustering of six strains according to
      their metabolites. We compared the metabolites among the strains, and found that
      a) the strains specialized for protein production were segregated; b) XL1-Blue
      separated itself from others by accumulating amino acids such as alanine,
      aspartate, glutamate, methionine, proline, and lysine; c) the strains specialized
      for cloning purpose were spread out from one another; and d) the strains
      originating from B strain were characterized by succinate accumulation. This work
      shows that 2D-NMR can be applied to identify a strain from metabolite analysis,
      offering a possible alternative to genetic analysis to identify E. coli strains. 

PMID- 24130026
TI  - Immobilization of 5-fluorouridine on chitosan.
AB  - The 2',3'-O-levulinic acid derivative 2b of the cancerostatic 5-fluorouridine as
      well as its N(3)-farnesylated nucleolipid 2d were synthesized and coupled to H2 O
      soluble chitosanes of different molecular weight and at various pH values (3.5
      5.5) leading to 6 and 7. In addition, the coumarine fluorophore ATTO-488 N(9)
      butanoate was bound to the biopolymer by a sequential-coupling technique to
      afford 9 and 10. Moreover, chitosan foils were prepared, to which 2b was coupled.
      Their degradation by chitosanase (from Streptomyces sp. N174) was studied UV
      spectrophotometrically in a Franz diffusion cell. 

PMID- 24130027
TI  - Identification and quantitation of new glutamic acid derivatives in soy sauce by
      UPLC/MS/MS.
AB  - Glutamic acid is an abundant amino acid that lends a characteristic umami taste
      to foods. In fermented foods, glutamic acid can be found as a free amino acid
      formed by proteolysis or as a non-proteolytic derivative formed by
      microorganisms. The aim of the present study was to identify different structures
      of glutamic acid derivatives in a typical fermented protein-based food product,
      soy sauce. An acidic fraction was prepared with anion-exchange solid-phase
      extraction (SPE) and analyzed by UPLC/MS/MS and UPLC/TOF-MS. alpha-Glutamyl,
      gamma-glutamyl, and pyroglutamyl dipeptides, as well as lactoyl amino acids, were
      identified in the acidic fraction of soy sauce. They were chemically synthesized
      for confirmation of their occurrence and quantified in the selected reaction
      monitoring (SRM) mode. Pyroglutamyl dipeptides accounted for 770 mg/kg of soy
      sauce, followed by lactoyl amino acids (135 mg/kg) and gamma-glutamyl dipeptides
      (70 mg/kg). In addition, N-succinoylglutamic acid was identified for the first
      time in food as a minor compound in soy sauce (5 mg/kg). 

PMID- 24130028
TI  - Glycosidic inhibitors of melanogenesis from leaves of Passiflora edulis.
AB  - A new flavonoid glycoside, chrysin 6-C-beta-rutinoside (chrysin alpha-L
      rhamnopyranosyl-(1->6)-C-beta-glucopyranoside; 2), and two new triterpene
      glycosides, (31R)-31-O-methylpassiflorine (7) and (31S)-31-O-methylpassiflorine
      (8), along with 14 known glycosides, including three flavonoid glycosides, 1, 3,
      and 4, six triterpene glycosides, 5, 6, and 9-12, three cyano glycosides, 13-15,
      and two other glycosides, 16 and 17, were isolated from a MeOH extract of the
      leaves of Passiflora edulis (passion flower; Passifloraceae). The structures of
      new compounds were elucidated on the basis of extensive spectroscopic analysis
      and comparison with literature data. Upon evaluation of compounds 1-17 against
      the melanogenesis in the B16 melanoma cells induced with alpha-melanocyte
      stimulating hormone (alpha-MSH), three compounds, isoorientin (1), 2, and (6S,9R)
      roseoside (17), exhibited inhibitory effects with 37.3-47.2% reduction of melanin
      content with no, or almost no, toxicity to the cells (90.8-100.2% cell viability)
      at 100 MUM. Western blot analysis showed that compound 2 reduced the protein
      levels of MITF, TRP-1, and tyrosinase, in a concentration-dependent manner while
      exerted almost no influence on the level of TRP-2, suggesting that this compound
      inhibits melanogenesis on the alpha-MSH-stimulated B16 melanoma cells by, at
      least in part, inhibiting the expression of MITF, followed by decreasing the
      expression of TRP-1 and tyrosinase. In addition, compounds 1-17 were evaluated
      for their inhibitory effects against the Epstein?Barr virus early antigen (EBV
      EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji
      cells. 

PMID- 24130029
TI  - Cancer chemopreventive effect of bergenin from Peltophorum pterocarpum wood.
AB  - The aqueous extract of Peltophorum pterocarpum (Fabaceae) wood exhibited potent
      inhibitory effects against Epstein?Barr virus early antigen (EBV-EA) activation
      induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and against
      melanogenesis in alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated B16
      melanoma cells, as well as potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
      radical-scavenging activity. Two phenolic acid derivatives, bergenin (1) and
      gallic acid (2), were isolated from the ethyl acetate (AcOEt)-soluble fraction
      obtained from the extract. Compound 1 exhibited potent inhibitory effect against
      EBV-EA activation and against skin tumor promotion in an in vivo two-stage mouse
      skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as
      initiator, and with TPA as promoter. Both compounds 1 and 2 exhibited
      melanogenesis-inhibitory activities in alpha-MSH-stimulated B16 melanoma cells,
      and, in addition, compound 2 showed strong DPPH radical-scavenging activity. 

PMID- 24130030
TI  - Chemical composition and biological activities of the essential oil of Athanasia
      brownii Hochr. (Asteraceae) endemic to Madagascar.
AB  - The essential oil obtained from hydrodistillation of flowering aerial parts of
      Athanasia brownii (Asteraceae) was studied for its chemical composition by GC/FID
      and GC/MS, and for biological activity, namely, antioxidant, antimicrobial, and
      chemopreventive potential, by DPPH (=2,2-diphenyl-1-picrylhydrazyl), ABTS (=2,2'
      azinobis[3-ethylbenzothioline-6-sulfonic acid), and FRAP (=ferric reducing
      antioxidant power), disk diffusion test, and MTT (=3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide) assay, respectively. The oil was characterized
      by a high content of oxygenated sesquiterpenes (71.2%), with selin-11-en-4alpha
      ol (24.6%), caryophyllene oxide (8.7%), humulene epoxide II (5.1%), and (E)
      nerolidol (4.9%) as the predominant compounds. The oil showed a moderate activity
      against streptococci as well as radical-scavenging potential, while the
      inhibitory effects against human cancer cells examined such as A375 (malignant
      melanoma) and HCT 116 (colon carcinoma) were significant, with IC50 values of
      19.85 and 29.53 MUg/ml, respectively. 

PMID- 24130031
TI  - Norlathyrane diterpenes from the root of Euphorbia kansuensis.
AB  - Phytochemical investigation of the EtOH extract obtained from the root of the
      Euphorbia kansuensis Proch. grown in China resulted in the isolation of two novel
      norlathyrane diterpenes, named ekanpenoids A and B (1 and 2, resp.). Their
      structures were established by extensive 1D- and 2D-NMR spectroscopy, as well as
      other spectra. The isolated diterpenes exhibited potent cytotoxic activities
      against the HeLa and Hep-G2 cell lines with the IC50 values ranging from 3.6 to
      9.7 MUg/ml. 

PMID- 24130032
TI  - Composition and antiviral activity of the essential oils of Eryngium alpinum and
      E. amethystinum.
AB  - The chemical compositions of the essential oils obtained by hydrodistillation of
      the aerial parts of Croatian Eryngium alpinum L. and E. amethystinum L. were
      characterized by GC-FID and GC/MS analyses. The main components identified were
      the sesquiterpene beta-caryophyllene (19.7%) in the oil of E. amethystinum and
      the oxygenated sesquiterpene caryophyllene oxide (21.6%) in the oil of E.
      alpinum. Overall, 32 and 35 constituents were detected in the essential oils of
      the aerial parts of E. alpinum and E. amethystinum, respectively, representing
      92.4 and 93.1% of the total oil compositions. The essential oils of both Eryngium
      species were proved to reduce the number of lesions in the local host Chenopodium
      quinoa infected with cucumber mosaic virus and an associated satellite. This is
      the first investigation of antiphytoviral activity of essential oils of Eryngium
      species. 

PMID- 24130033
TI  - New pterosin sesquiterpenes and antitubercular constituents from Pteris
      ensiformis.
AB  - Two new pterosin sesquiterpenes, (2S)-13-hydroxypterosin A (1) and (2S,3S)-12
      hydroxypterosin Q (2), were isolated from the whole plants of Pteris ensiformis,
      together with six known compounds. The structures of 1 and 2 were determined
      through extensive 1D/2D-NMR and MS analyses. Compound 2 exhibited antitubercular
      activity (MIC 6.25 MUg/ml) against Mycobacterium tuberculosis H37 Rv in vitro. 

PMID- 24130034
TI  - Biotransformations of terpenes by fungi from Amazonian citrus plants.
AB  - The biotransformations of (RS)-linalool (1), (S)-citronellal (2), and sabinene
      (3) with fungi isolated from the epicarp of fruits of Citrus genus of the
      Amazonian forest (i.e., C. limon, C. aurantifolia, C. aurantium, and C.
      paradisiaca) are reported. The more active strains have been characterized, and
      they belong to the genus Penicillium and Fusarium. Different biotransformation
      products have been obtained depending on fungi and substrates. (RS)-Linalool (1)
      afforded the (E)- and (Z)-furanlinalool oxides (7 and 8, resp.; 39 and 37% yield,
      resp.) with Fusarium sp. (1D2), 6-methylhept-5-en-2-one (4; 49%) with F.
      fujikuroi, and 1-methyl-1-(4-methypentyl)oxiranemethanol (6; 42%) with F.
      concentricum. (S)-Citronellal (2) gave (S)-citronellol (12; 36-76%) and (S)
      citronellic acid (11; 5-43%) with Fusarium species, while diastereoisomeric p
      menthane-3,8-diols 13 and 14 (20 and 50% yield, resp.) were obtained as main
      products with Penicillium paxilli. Finally, both Fusarium species and P. paxilli
      biotransformed sabinene (3) to give mainly 4-terpineol (19; 23-56%), and (Z)- and
      (E)-sabinene hydrates (17 (3-21%) and 18 (11-17%), resp.). 

PMID- 24130036
TI  - An iron/amine-catalyzed cascade process for the enantioselective
      functionalization of allylic alcohols.
AB  - Three is a lucky number: An enantioselective transformation of allylic alcohols
      into beta-chiral saturated alcohols has been developed by combining two distinct
      metal- and organocatalyzed catalytic cycles. This waste-free triple cascade
      process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed
      nucleophilic addition reaction. 

PMID- 24130037
TI  - Effect of chitosan conduit under a dynamic culture on the proliferation and
      neural differentiation of human exfoliated deciduous teeth stem cells.
AB  - Ex vivo engineering of artificial nerve conduit is a suitable alternative
      clinical treatment for nerve injuries. Stem cells from human exfoliated deciduous
      teeth (SHEDs) have been considered as alternative sources of adult stem cells
      because of their potential to differentiate into multiple cell lineages. These
      cells, when cultured in six-well plates, exhibited a spindle fibroblastic
      morphology, whereas those under a dynamic culture aggregated into neurosphere
      like clusters in the chitosan conduit. In this study, we confirmed that SHEDs
      efficiently express the neural stem cell marker nestin, the early neural cell
      marker beta-III-tubulin, the late neural marker neuron-specific enolase and the
      glial cell markers glial fibrillary acidic protein (GFAP) and 2',3'-cyclic
      nucleotide-3'-phosphodiesterase (CNPase). The three-dimensional chitosan conduit
      and dynamic culture system generated fluid shear stress and enhanced nutrient
      transfer, promoting the differentiation of SHEDs to neural cells. In particular,
      the gene expressions of GFAP and CNPase increased by 28- and 53-fold,
      respectively. This study provides evidence for the dynamic culture of SHEDs
      during ex vivo neural differentiation and demonstrates its potential for cell
      therapy in neurological diseases. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24130038
TI  - Supramolecular hierarchy among halogen-bond donors.
AB  - Through a combination of structural chemistry, vibrational spectroscopy, and
      theory, we have systematically examined the relative structure-directing
      importance of a series of ditopic halogen-bond (XB) donors. The molecular
      electrostatic potential surfaces of six XB donors were evaluated, which allowed
      for a charge-based ranking. Each molecule was then co-crystallized with 21 XB
      acceptors and the results have made it possible to map out the supramolecular
      landscape describing the competition between I/Br-ethynyl donors, perfluorinated
      I/Br donors, and I/Br-phenyl based donors. The results offer practical guidelines
      for synthetic crystal engineering driven by robust and directional halogen bonds.

PMID- 24130039
TI  - Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated
      with curcumin and/or insulin.
AB  - This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme
      activity in blood, liver, and kidney, as well as on lipid peroxidation and delta
      aminolevulinic dehydratase (delta-ALA-D) activity, and a histopathological
      analysis of streptozotocin-induced diabetic rats. The animals were divided into
      six groups (n = 6): control/saline (C); control/curcumin (CCur); diabetic/saline
      (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and
      diabetic/insulin/curcumin (DInsCur). After 30 days of treatment with curcumin
      and/or insulin, the animals were sacrificed and the liver, kidney, and serum were
      used for experimental determinations. Results of histopathological analysis
      showed that the treatment with insulin ameliorate renal and hepatic lesions from
      both DIns and DInsCur groups. TBARS levels were significantly increased in serum,
      liver, and kidney in D group and the administration of curcumin and insulin
      prevented this increase in DIns and DCur groups. The activities of catalase
      (CAT), superoxide dismutase, and delta-ALA-D presented a significant decrease in
      the liver and kidney D group when compared to C group (P < 0.05). The animals
      treated with curcumin and insulin presented an increase of CAT activity,
      revealing a positive interaction between both substances. The treatments with
      curcumin or insulin prevented oxidative stress in blood, through modulation of
      enzymatic antioxidant defenses. These findings contributed to the comprehension
      that antioxidants from medicinal plants could be used as adjuvant in the
      treatment of this endocrinopathy and not as single therapy. 

PMID- 24130040
TI  - Wnt/beta-catenin signaling mediates the senescence of bone marrow-mesenchymal
      stem cells from systemic lupus erythematosus patients through the p53/p21
      pathway.
AB  - Recent studies have shown that allogeneic bone marrow (BM)-mesenchymal stem cell
      transplantation (MSCT) appears to be effective in systemic lupus erythematosus
      (SLE) patients and lupus-prone mice, contrary to studies in syngeneic BM-MSCT.
      These studies indicated that the abnormalities of BM-MSCs may be involved in the
      pathogenesis of SLE. Our studies and other previous studies have revealed that BM
      MSCs from SLE patients exhibited early signs of senescence, such as flattened
      morphology, slow proliferation, increased senescence-associated beta
      galactosidase (SA-beta-gal) activity, and so on. However, the mechanisms by which
      these cells senescences were still unclear. Previous studies have demonstrated
      that Wnt/beta-catenin signaling plays an important role in stem cell senescence.
      In the current study, we investigated whether Wnt/beta-catenin signaling mediates
      the senescence of BM-MSCs from SLE patients. We have found that Wnt/beta-catenin
      signaling and the p53/p21 pathway were significantly hyperactivated in senescent
      SLE BM-MSCs. Treatment with 100 ng/mL Dickkopf-1 (DKK1), a Wnt/beta-catenin
      signaling inhibitor or beta-catenin siRNA for 48 h could reverse the senescent
      features of SLE BM-MSCs. Additionally, the expression levels of p53 and p21 were
      reduced in treated-SLE BM-MSCs compared with the untreated group. In summary, our
      study indicated that Wnt/beta-catenin signaling may play a critical role in the
      senescence of SLE BM-MSCs through the p53/p21 pathway.

PMID- 24130041
TI  - Anatomical basis for the low incidence of internal hernia after a laparoscopic
      Roux-en-Y gastric bypass without mesenteric closure.

PMID- 24130042
TI  - Author's response: Anatomical basis for the low incidence of internal hernia
      after a laparoscopic Roux-en-Y gastric bypass without mesenteric closure.

PMID- 24130043
TI  - Predicting acute and chronic effects of wood preservative products in Daphnia
      magna and Pseudokirchneriella subcapitata based on the concept of concentration
      addition.
AB  - The current European legislation requires that combined effects of the active
      substances and any substance of concern contained in biocidal products are taken
      into account in environmental risk assessment. The hypothesis whether the
      consideration of active substances together with all formulation additives that
      are labeled as presenting an environmental hazard is sufficient for a reliable
      environmental risk assessment was tested in the present study by investigating 3
      wood preservative products. Relevant single substances in the products, some of
      their generic mixtures, the biocidal products themselves, and aqueous eluates
      prepared from the products (representing potential environmental mixtures) were
      tested for effects on algal growth and Daphnia acute immobilization as well as
      reproduction. Predictions for the products and the eluates were based on the
      concept of concentration addition and were mostly found to provide reliable or at
      least protective estimates for the observed acute and chronic toxicity of the
      mixtures. The mixture toxicity considerations also indicated that the toxicity of
      each product was dominated by just 1 of the components, and that assessments
      based only on the dominating substance would be similarly protective as a full
      mixture risk assessment. Yet, there remained uncertainty in some cases that could
      be related to the toxicity of transformation products, the impact of unidentified
      formulation additives, or synergistic interaction between active substances and
      formulation additives.

PMID- 24130044
TI  - The vocal repertoire of adult male blue monkeys (Cercopithecus mitis stulmanni):
      a quantitative analysis of acoustic structure.
AB  - Vocal signals are key elements in understanding species' behavior, sociality, and
      evolution. Quantified repertoires serve as foundations for investigating usage
      and function of particular signals, and also provide a basis for comparative
      analyses among individuals, populations, and taxa to explore how entire signal
      systems evolve. This study presents a descriptive catalogue of all vocal signals
      used by adult male blue monkeys (Cercopithecus mitis stuhlmanni). During 12
      months in the Kakamega Forest, Kenya, I observed and digitally recorded vocal
      behavior of 32 adult males across a variety of socioecological contexts. From
      recordings, I measured 18 temporal-frequency parameters. Undirected ordination
      and hierarchical cluster analysis identified six distinct call types regularly
      used by males: ant, boom, ka, katrain, nasal scream, and pyow. Cross-validated
      discriminant function analysis supported the classifications. The repertoire is
      best described as discrete, though some gradation occurs between pyows and ants.
      Summary of acoustic structure and exemplar spectrograms are provided for each
      call type, along with preliminary examination of socioecological contexts in
      which they were produced. Discussion addresses repertoire structure, similarity
      to other taxa, and potential for functional inferences.

PMID- 24130045
TI  - Detection and characterization of 1,2-dibromoethane-derived DNA crosslinks formed
      with O(6) -alkylguanine-DNA alkyltransferase.
AB  - A combination of chemical modifications and LC-tandem MS was used for the
      structure elucidation of various ethylene crosslinks of DNA with O(6) 
      alkylguanine-DNA alkyltransferase (AGT, see picture). The elucidation of the
      chemical structures of such DNA-protein crosslinks is necessary to understand
      mechanisms of mutagenesis. 

PMID- 24130046
TI  - Using poison center exposure calls to predict prescription opioid abuse and
      misuse-related emergency department visits.
AB  - BACKGROUND: Prescription drug abuse is a critical problem in the USA and has been
      linked to more deaths than automobile accidents. Despite this growing epidemic,
      the USA lacks a timely early warning system. Poison centers (PCs) have the
      potential to act as sentinel reporting entities for prescription drug abuse and
      misuse due to near-real-time data reporting and abundant coverage in the USA.
      METHODS: Data from the Researched Abuse, Diversion and Addiction-Related
      Surveillance (RADARS(r)) System PC program were compared with data from the Drug
      Abuse Warning Network (DAWN) from 2004 through 2010. Population rates of PC call
      mentions regarding abuse and misuse of prescription opioids were compared with
      population rates of emergency department visit mentions of the same using linear
      regression. Products included in the analysis were the following: buprenorphine,
      fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone.
      RESULTS: The strength of association between RADARS System PC data and DAWN
      emergency department visits regarding all opioids in aggregate was strong (R2 =
      0.81, p < 0.001). The correlations between the two programs at the drug class
      level also were strong for buprenorphine, hydrocodone, hydromorphone, methadone,
      and oxycodone (all R2 > 0.70, all p < 0.01), significant for fentanyl (p = 0.05),
      and moderate for morphine (p = 0.09). CONCLUSIONS: Data on prescription opioid
      drug abuse from the RADARS System PC program correlates well with emergency room
      data from DAWN. Due to timeliness of data, geographic coverage and strong
      associations with other warning systems, PC data can be used for sentinel
      reporting on prescription drug abuse and misuse in the USA.

PMID- 24130047
TI  - Self-assembly of alpha-helices to form rare two-dimensional square P4mm symmetry
      via silica mineralization.
AB  - Space oddity: The synthesis of a polypeptide-silica complex with a rare two
      dimensional square P4mm structure is reported. The electrostatic "zipping" of the
      interacting amino and carboxylate groups along the alpha-helices and the diagonal
      formation of the silica wall between the alpha-helices were optimal for the
      identical azimuthal orientation of alpha-helices toward 2D square P4mm structure,
      which generated a new polypeptide liquid crystal phase diagram. 

PMID- 24130048
TI  - The practical application of narrative medicine at Mayo Clinic: imagining the
      scaffold of a worthy house.
AB  - American health care institutions increasingly recognize narrative medicine as a
      means to developing quality patient care. More commonly applied in health care
      professional development settings, narrative medicine is less overtly employed
      with patient populations. In this article, we describe the application of various
      narrative practices in the patient care and medical education programs of a major
      health care center in Minnesota. We discuss the impact of these programs on their
      participants in relation to the evidence based in current scholarship. Further,
      we examine narrative externalization of illness in Katherine Butler Hathaway's
      disability memoir "The Little Locksmith," a text which implicates the work of
      metaphor-making as a transformative step in healing. While several reports
      demonstrate that patients can find creative writing during times of illness to be
      therapeutic, there are many for whom the practice is problematic or unattractive,
      obstacles to practice implementation that the authors discuss. However, based on
      the experience of our institution, for health care institutions seeking to build
      a legacy of leadership in empathic patient care, narrative--employed in mentoring
      physicians in training and in establishing strong, dialogic relationships with
      patients and colleagues--should serve as a central strategy, or scaffold.

PMID- 24130050
TI  - Tunicamycin potentiates cisplatin anticancer efficacy through the
      DPAGT1/Akt/ABCG2 pathway in mouse Xenograft models of human hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma is highly chemoresistant, and ATP-binding cassette
      subfamily G member 2 (ABCG2) is thought to play a critical role in this drug
      resistance. The present study aims to develop effective therapeutic strategies to
      decrease ABCG2 expression level and to surmount drug resistance in hepatocellular
      carcinoma chemotherapy. First, we verified a positive correlation between the
      ABCG2 protein level and the drug resistance of hepatocellular carcinoma cell
      lines. ABCG2 was preferentially expressed in highly chemoresistant hepatocellular
      carcinoma cancer stem cells (CSC) enriched with CD133. In addition, ABCG2 was N
      linked glycosylated in hepatocellular carcinoma cells, and this modification was
      involved in sustaining its protein stability. The N-linked glycosylation (NLG)
      inhibitor tunicamycin dramatically reduced ABCG2 expression, altered its
      subcellular localization, and reversed its drug efflux effect in multiple
      hepatocellular carcinoma cell lines. Furthermore, tunicamycin reduced the
      expression levels of several CSC markers and suppressed the tumorigenicity of
      CD133(+) CSCs. Tunicamycin combined with cisplatin (CDDP) inhibited proliferating
      cell nuclear antigen (PCNA) expression and increased the cleavage of PARP; this
      effect was partially rescued by the overexpression of ABCG2 or Akt-myr. The
      combination therapy more effectively suppressed tumor growth in xenograft mice
      than did single-agent therapy with either drug. Finally, the CDDP treatment
      combined with UDP-GlcNAc-dolichol-phosphate N-acetylglucosamine-1 phosphate
      transferase (DPAGT1) knockdown recapitulated the effect observed when CDDP was
      used in combination with tunicamycin. In summary, our results suggest that
      tunicamycin may reverse the drug resistance and improve the efficacy of
      combination treatments for hepatocellular carcinomas by targeting the
      DPAGT1/Akt/ABCG2 pathway.

PMID- 24130049
TI  - IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small
      cell lung cancer cells.
AB  - Insulin-like growth factor (IGF)-binding protein-2 (IGFBP2) expression is
      increased in various types of cancers, including in a subset of patients with
      lung cancer. Because IGFBP2 is involved in signal transduction of some critical
      cancer-related pathways, we analyzed the association between IGFBP2 and response
      to pathway-targeted agents in seven human non-small cell lung cancer (NSCLC) cell
      lines. Western blot analysis and ELISA showed that four of the seven NSCLC cell
      lines analyzed expressed high levels of IGFBP2, whereas the remaining three had
      barely detectable IGFBP2. Susceptibilities of those seven cell lines to nine
      anticancer agents targeting to IGF1R, Src, FAK, MEK, and AKT were determined by a
      dose-dependent cell viability assay. The results showed that high IGFBP2 levels
      were associated with resistance to dasatinib and, to a lesser degree, to
      sacaratinib, but not to other agents. Ectopic IGFBP2 overexpression or knockdown
      revealed that changing IGFBP2 expression levels reversed dasatinib susceptibility
      phenotype, suggesting a causal relationship between IGFBP2 expression and
      dasatinib resistance. Molecular characterization revealed that focal adhesion
      kinase (FAK) activation was associated with increased IGFBP2 expression and
      partially contributed to IGFBP2-mediated dasatinib resistance. Treatment with a
      combination of dasatinib and FAK inhibitor led to enhanced antitumor activity in
      IGFBP2-overexpressing and dasatinib-resistant NSCLC cells in vitro and in vivo.
      Our results showed that the IGFBP2/FAK pathway is causally associated with
      dasatinib resistance and may be used as biomarkers for identification of
      dasatinib responders among patients with lung cancer. Simultaneous targeting on
      Src and FAK will likely improve the therapeutic efficacy of dasatinib for
      treatment of lung cancer.

PMID- 24130051
TI  - Long pentraxin-3 inhibits epithelial-mesenchymal transition in melanoma cells.
AB  - During melanoma progression, malignant melanocytes are reprogrammed into
      mesenchymal-like cells through to an epithelial-mesenchymal transition (EMT)
      process associated with the acquisition of an invasive, prometastatic phenotype.
      The fibroblast growth factor-2 (FGF2)/FGF receptor (FGFR) system plays a pivotal
      role in melanoma, leading to autocrine/paracrine induction of tumor cell
      proliferation and angiogenesis. Long pentraxin-3 (PTX3) interacts with FGF2, and
      other FGF family members, inhibiting FGF-dependent neovascularization and tumor
      growth. Here, PTX3 protein and the PTX3-derived acetylated pentapeptide Ac-ARPCA
      NH2 inhibit FGF2-driven proliferation and downstream FGFR signaling in murine
      melanoma B16-F10 cells. Moreover, human PTX3-overexpressing hPTX_B16-F10 cells
      are characterized by the reversed transition from a mesenchymal to an epithelial
      like appearance, inhibition of cell proliferation, loss of clonogenic potential,
      reduced motility and invasive capacity, downregulation of various mesenchymal
      markers, and upregulation of the epithelial marker E-cadherin. Accordingly, PTX3
      affects cell proliferation and EMT transition in human A375 and A2058 melanoma
      cells. Also, hPTX_B16-F10 cells showed a reduced tumorigenic and metastatic
      activity in syngeneic C57BL/6 mice. In conclusion, PTX3 inhibits FGF/FGFR-driven
      EMT in melanoma cells, hampering their tumorigenic and metastatic potential.
      These data represent the first experimental evidence about a nonredundant role of
      the FGF/FGFR system in the modulation of the EMT process in melanoma and indicate
      that PTX3 or its derivatives may represent the basis for the design of novel
      therapeutic approaches in FGF/FGFR-dependent tumors, including melanoma.

PMID- 24130052
TI  - Sym004, a novel anti-EGFR antibody mixture, augments radiation response in human
      lung and head and neck cancers.
AB  - Sym004 represents a novel EGF receptor (EGFR)-targeting approach comprising a
      mixture of two anti-EGFR antibodies directed against distinct epitopes of EGFR.
      In contrast with single anti-EGFR antibodies, Sym004 induces rapid and highly
      efficient degradation of EGFR. In the current study, we examine the capacity of
      Sym004 to augment radiation response in lung cancer and head and neck cancer
      model systems. We first examined the antiproliferative effect of Sym004 and
      confirmed 40% to 60% growth inhibition by Sym004. Using clonogenic survival
      analysis, we identified that Sym004 potently increased cell kill by up to 10-fold
      following radiation exposure. A significant increase of gammaH2AX foci resulting
      from DNA double-strand breaks was observed in Sym004-treated cells following
      exposure to radiation. Mechanistic studies further showed that Sym004 enhanced
      radiation response via induction of cell-cycle arrest followed by induction of
      apoptosis and cell death, reflecting inhibitory effects on DNA damage repair. The
      expression of several critical molecules involved in radiation-induced DNA damage
      repair was significantly inhibited by Sym004, including DNAPK, NBS1, RAD50, and
      BRCA1. Using single and fractionated radiation in human tumor xenograft models,
      we confirmed that the combination of Sym004 and radiation resulted in significant
      tumor regrowth delay and superior antitumor effects compared with treatment with
      Sym004 or radiation alone. Taken together, these data reveal the strong capacity
      of Sym004 to augment radiation response in lung and head and neck cancers. The
      unique action mechanism of Sym004 warrants further investigation as a promising
      EGFR targeting agent combined with radiotherapy in cancer therapy.

PMID- 24130053
TI  - Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells.
AB  - Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the
      proliferation and progression of many cancer types, including leukemia. However,
      the ID1 protein has not yet been therapeutically targeted in leukemia. ID1 is
      normally polyubiquitinated and degraded by the proteasome. Recently, it has been
      shown that USP1, a ubiquitin-specific protease, deubiquitinates ID1 and rescues
      it from proteasome degradation. Inhibition of USP1 therefore offers a new avenue
      to target ID1 in cancer. Here, using a ubiquitin-rhodamine-based high-throughput
      screening, we identified small-molecule inhibitors of USP1 and investigated their
      therapeutic potential for leukemia. These inhibitors blocked the deubiquitinating
      enzyme activity of USP1 in vitro in a dose-dependent manner with an IC50 in the
      high nanomolar range. USP1 inhibitors promoted the degradation of ID1 and,
      concurrently, inhibited the growth of leukemic cell lines in a dose-dependent
      manner. A known USP1 inhibitor, pimozide, also promoted ID1 degradation and
      inhibited growth of leukemic cells. In addition, the growth of primary acute
      myelogenous leukemia (AML) patient-derived leukemic cells was inhibited by a USP1
      inhibitor. Collectively, these results indicate that the novel small-molecule
      inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells.
      The identification of USP1 inhibitors therefore opens up a new approach for
      leukemia therapy.

PMID- 24130054
TI  - Differential and common DNA repair pathways for topoisomerase I- and II-targeted
      drugs in a genetic DT40 repair cell screen panel.
AB  - Clinical topoisomerase I (Top1) and II (Top2) inhibitors trap topoisomerases on
      DNA, thereby inducing protein-linked DNA breaks. Cancer cells resist the drugs by
      removing topoisomerase-DNA complexes, and repairing the drug-induced DNA double
      strand breaks (DSB) by homologous recombination and nonhomologous end joining
      (NHEJ). Because numerous enzymes and cofactors are involved in the removal of the
      topoisomerase-DNA complexes and DSB repair, it has been challenging to
      comprehensively analyze the relative contribution of multiple genetic pathways in
      vertebrate cells. Comprehending the relative contribution of individual repair
      factors would give insights into the lesions induced by the inhibitors and
      genetic determinants of response. Ultimately, this information would be useful to
      target specific pathways to augment the therapeutic activity of topoisomerase
      inhibitors. To this end, we put together 48 isogenic DT40 mutant cells deficient
      in DNA repair and generated one cell line deficient in autophagy (ATG5).
      Sensitivity profiles were established for three clinically relevant Top1
      inhibitors (camptothecin and the indenoisoquinolines LMP400 and LMP776) and three
      Top2 inhibitors (etoposide, doxorubicin, and ICRF-193). Highly significant
      correlations were found among Top1 inhibitors as well as Top2 inhibitors, whereas
      the profiles of Top1 inhibitors were different from those of Top2 inhibitors.
      Most distinct repair pathways between Top1 and Top2 inhibitors include NHEJ,
      TDP1, TDP2, PARP1, and Fanconi Anemia genes, whereas homologous recombination
      seems relevant especially for Top1 and, to a lesser extent, for Top2 inhibitors.
      We also found and discuss differential pathways among Top1 inhibitors and Top2
      inhibitors.

PMID- 24130055
TI  - Cytoreductive chemotherapy improves the biodistribution of antibodies directed
      against tumor necrosis in murine solid tumor models.
AB  - Current strategies in cancer treatment employ combinations of different treatment
      modalities, which include chemotherapy, radiotherapy, immunotherapy, and surgery.
      Consistent with that approach, the present study demonstrates how
      chemotherapeutic agents can potentiate the delivery of radiolabeled, necrosis
      targeting antibodies (chTNT-3, NHS76) to tumor. All chemotherapeutics in this
      study (5-fluorouracil, etoposide, vinblastine, paclitaxel, and doxorubicin)
      resulted in statistically significant increases in tumor uptake of radiolabeled
      antibodies and their F(ab')2 fragments compared to no pretreatment with
      chemotherapy. Labeled antibodies were administered at various time points
      following a single dose of chemotherapy in multiple tumor models, and the
      biodistribution of the antibodies was determined by measuring radioactivity in
      harvested tissues. MicroPET/CT was also done to demonstrate clinical relevancy of
      using chemotherapy pretreatment to increase antibody uptake. Results of
      biodistribution and imaging data reveal specific time frames following
      chemotherapy when necrosis-targeting antibodies are best delivered, either for
      imaging or radiotherapy. Thus, the present work offers the prospect of using
      cytoreductive chemotherapy to increase tumor accumulation of select therapeutic
      antibodies, especially when combined with other forms of immunotherapy, for the
      successful treatment of solid tumors.

PMID- 24130056
TI  - Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth.
AB  - Ovarian cancer mortality ranks highest among all gynecologic cancers with growth
      factor pathways playing an integral role in tumorigenesis, metastatic
      dissemination, and therapeutic resistance. The HER and VEGF receptor (VEGFR) are
      both overexpressed and/or aberrantly activated in subsets of ovarian tumors.
      While agents targeting either the HER or VEGF pathways alone have been
      investigated, the impact of these agents have not led to overall survival benefit
      in ovarian cancer. We tested the hypothesis that cotargeting HER and VEGFR would
      maximize antitumor efficacy at tolerable doses. To this end, ovarian cancer
      xenografts grown intraperitoneally in athymic nude mice were tested in response
      to AC480 (pan-HER inhibitor, "HERi"), cediranib (pan-VEGFR inhibitor "VEGFRi"),
      or BMS-690514 (combined HER/VEGFR inhibitor "EVRi"). EVRi was superior to both
      HERi and VEGFRi in terms of tumor growth, final tumor weight, and progression
      free survival. Correlative tumor studies employing phosphoproteomic antibody
      arrays revealed distinct agent-specific alterations, with EVRi inducing the
      greatest overall effect on growth factor signaling. These data suggest that
      simultaneous inhibition of HER and VEGFR may benefit select subsets of ovarian
      cancer tumors. To this end, we derived a novel HER/VEGF signature that correlated
      with poor overall survival in high-grade, late stage, serous ovarian cancer
      patient tumors.

PMID- 24130057
TI  - Spectrophotometric simultaneous determination of metal ions in cows' milk and
      vegetables with the aid of artificial neural networks using synthetic 2
      benzylspiro[isoindoline-1,5'-oxazolidine]-2',3,4'-trione.
AB  - BACKGROUND: A simple, selective and sensitive multi-component method for the
      simultaneous determination of Zn(2+) , Mn(2+) and Fe(3+) based on complex
      formation with 2-benzylspiro[isoindoline-1,5'-oxazolidine]-2',3,4'-trione using
      artificial neural networks is proposed. RESULTS: The analytical data showed that
      metal-to-ligand ratios in Zn(2+) and Fe(3+) complexes was 1:1 and for Mn(2+)
      complex was 1:2. It was found at pH 6.5 and 5 min after mixing, the complexation
      reactions were completed. The coloured complexes exhibited absorption bands in
      the wavelength range 200-400 nm. The results showed that Zn(2+) , Mn(2+) and
      Fe(3+) could be determined in the range 0.1-18.0, 0.3-10.0 and 0.5-20.0 mg L(-1)
      , respectively. CONCLUSION: The data obtained from synthetic mixtures of metal
      ions were processed by radial basis function networks (RBFNs) and back
      propagation neural network. The optimal conditions of the neural networks were
      obtained by adjusting various parameters. Satisfactory precision and accuracy
      were obtained with all networks, although, because of surprisingly lower root
      mean square error (%) values, RBFNs were the preferred approach. The proposed
      approach was tested by analysing the composition of the different mixtures
      containing Zn(2+) , Mn(2+) and Fe(3+) . The proposed method was successfully
      applied to the simultaneous determination of Zn(2+) , Mn(2+) and Fe(3+) ions in
      milk and vegetable samples.

PMID- 24130058
TI  - Washoff of cypermethrin residues from slabs of external building material
      surfaces using simulated rainfall.
AB  - The use of pesticides by homeowners or pest-control operators in urban settings
      is common, yet contributions of washoff from these materials are not easily
      understood. In the present study, cypermethrin, formulated as Cynoff EC
      (emulsifiable concentrate) and Cynoff WP (wettable powder) insecticides, was
      applied at typical rates to 10 different building material surfaces to examine
      its washoff potential from each surface. Using an indoor rainfall simulator, a 1
      h rainfall event was generated and washoff samples were collected from 3
      replicates of each surface type. Washoff was analyzed for cypermethrin using gas
      chromatography-negative chemical ionization mass spectrometry. An analysis of
      variance for a split-plot design was performed. Many building materials had
      similar water runoff masses, but asphalt resulted in significantly reduced
      average water runoff masses (73% less). The Cynoff WP formulation generally
      produced greater cypermethrin washoff than the Cynoff EC formulation. In
      addition, results for both the WP and EC formulations indicated that smoother
      surfaces such as vinyl and aluminum siding had higher washoff (1.0-14.1% mean
      percentage of applied mass). Cypermethrin washoff from rough absorptive surfaces
      like concrete and stucco was lower and ranged from 0.1 to 1.3% and from 0 to
      0.2%, respectively, mean percentage of applied mass. Both building material
      surface and formulation play a significant role in cypermethrin washoff.

PMID- 24130059
TI  - Platelet-derived growth factor BB gene-released scaffolds: biosynthesis and
      characterization.
AB  - Tissue engineering generally requires three basic elements; stem/progenitor
      cells, inductive agents and a biomaterial scaffold; the latter is one of the key
      components which directly influences cellular activity and matrix formation.
      Commonly used scaffolds to repair defects in general do not induce stem cell
      recruitment, which is an essential element to tissue regeneration. In this study,
      fabrication of a scaffold which is capable of restoring damaged tissue through
      the recruitment of mesenchymal stem cells (MSCs) by gene therapy of the gene
      encoding platelet-derived growth factor-B (PDGF-B) was investigated. PDGF-B
      adenovirus (AdPDGF) was combined into novel mesoporous bioglass-silk fibrin
      scaffolds, which were characterized for their controlled release and sustained
      bioactivity. Our results demonstrate that these scaffolds can release PDGF-B
      adenovirus for up to 3 weeks and increase MSC recruitment, both in vitro and
      following subcutaneous implantation in mice. Osseous calvarial defects in mice
      further demonstrate the ability of these scaffolds to enhance tissue regeneration
      through stem cell homing. This study demonstrates the potent ability of host stem
      cells to regenerate tissue defects through recruitment of MSCs via gene therapy.
      Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24130060
TI  - Nanomechanical analysis of yeast cells in CdSe quantum dot biosynthesis.
AB  - QD biosynthesis affects the mechanical strength of yeast cells. The intracellular
      synthesis of CdSe QD in yeast cells incubated with Na2 SeO3 and subsequently with
      CdCl2 increases the glucan content of their cell walls, resulting in their
      enhanced mechanical strength. 

PMID- 24130061
TI  - Dietary variability in the western black crested gibbon (Nomascus concolor)
      inhabiting an isolated and disturbed forest fragment in Southern Yunnan, China.
AB  - Forest fragmentation and isolation can reduce the size of available habitat and
      lead to lower food availability for some primate species. The persistence of
      nonhuman primates in fragments depends largely on their ability to adjust their
      diet in response environmental change. The western black crested gibbon (Nomascus
      concolor) is distributed in northern Vietnam, northwestern Laos, and southwestern
      China, but little is known about its diet except from studies in the well
      protected forests of Mt. Wuliang and Mt. Ailao, central Yunnan. We studied food
      abundance and diet over 2 years in a small group surviving in an isolated and
      disturbed forest at Bajiaohe, southern Yunnan, and drew a comparison with the
      population at Dazhaizi in Mt. Wuliang. We found that gibbons at Bajiaohe consumed
      mostly fruit, but did not eat figs, unlike most other gibbon populations. Liana
      fruits and mature leaves were used as alternative foods during periods of tree
      fruit scarcity. Our results indicate that gibbons in Bajiaohe respond to habitat
      fragmentation and isolation by consuming a variety of plant species, depending on
      those that are locally available, and increasing time spent feeding on fruits of
      trees and lianas rather than increasing time spent consuming leaves.

PMID- 24130062
TI  - Perception of primary care pediatricians of effectiveness, acceptability, and
      availability of mental health services.
AB  - Approximately 20% of children in the United States meet the criteria for a
      psychosocial disorder; however, less than 25% of these children receive
      psychosocial services. A questionnaire assessed primary care pediatricians'
      (PCPs) perceptions of effectiveness, availability, and burden of treatment
      options for children's psychosocial difficulties and parents' acceptance and
      adherence with these treatments. Repeated measures analysis of variance found
      that PCPs are more likely to refer children with psychosocial problems to a
      mental health professional than to prescribe medication. PCPs prescribe
      medications more than counseling parents themselves or watchful waiting. PCPs
      reported children's behavior is more likely to improve with mental health
      services than with medication, though medication is the most available treatment.
      PCPs believe parent training programs are very effective for treating children's
      behavior problems, but believe parents are more accepting and compliant with
      other treatments. Findings indicate PCPs' perceptions of availability and
      acceptability of treatment options drive their treatment recommendations of
      psychosocial problems. 

PMID- 24130063
TI  - Risk factors for venous thromboembolism during pregnancy.
AB  - BACKGROUND: Pregnant women are at an increased risk of venous thromboembolism
      (VTE). Risk factors for VTE among pregnant women are not sufficiently
      investigated. PURPOSE: To examine pharmacological and non-pharmacological VTE
      risk factors during pregnancy (antepartum). METHODS: The population comprised all
      pregnant women in Denmark aged 15-50 giving birth 2003-2010. Pregnancies were
      linked on an individual level with national registers for hospital admissions and
      drug dispenses from pharmacies. Risk of first occurring VTE antepartum was
      examined with Cox regression models. RESULTS: Out of 299 810 pregnancies, 337
      experienced a VTE, incidence rate 1.1 (95% confidence interval [CI] 1.0-1.3) per
      1000 pregnancies. Being underweight (body mass index [BMI] < 18.5 kg/m(2) ) was
      associated with a decreased risk of VTE (hazard ratio [HR] 0.53 [CI 0.29-0.98])
      compared to normal weight (18.5 <= BMI < 25 kg/m(2) ). Overweight (25 <= BMI < 30
      kg/m(2) ) increased VTE risk (HR 1.30 [CI 1.01-1.67]) but obesity (BMI >= 30
      kg/m(2) ) was insignificant (HR 1.14 [CI 0.82-1.58]). A history of VTE was highly
      significant (HR 72.65 [CI 51.17-103.15]). The youngest (<20 years) and oldest
      (>=35 years) had insignificantly increased risks (HR 1.45 [CI 0.80-2.62] and HR
      1.31 [CI 0.98-1.75], respectively) compared to those aged 20-30 years. Sixteen
      groups of medications, including anti-infectious medications, hormones,
      aminosalicylic acid, insulin, and benzodiazepine derivatives, were associated
      with VTE. CONCLUSION: The risk of antepartum VTE was increased in women with
      prior VTE. Compared to normal weight women, being underweight decreased the risk
      of VTE whereas being overweight increased the risk. Also, the use of several
      medications was associated with increased risk of VTE.

PMID- 24130064
TI  - The efficiency of therapeutic erythrocytapheresis compared to phlebotomy: a
      mathematical tool for predicting response in hereditary hemochromatosis,
      polycythemia vera, and secondary erythrocytosis.
AB  - Recently, therapeutic erythrocytapheresis (TE) was suggested to be more efficient
      in depletion of red blood cells (RBC) compared to manual phlebotomy in the
      treatment of hereditary hemochromatosis (HH), polycythemia vera (PV), and
      secondary erythrocytosis (SE). The efficiency rate (ER) of TE, that is, the
      increase in RBC depletion achieved with one TE cycle compared to one phlebotomy
      procedure, can be calculated based on estimated blood volume (BV), preprocedural
      hematocrit (Hct(B)), and delta-hematocrit (DeltaHct). In a retrospective
      evaluation of 843 TE procedures (in 45 HH, 33 PV, and 40 SE patients) the mean ER
      was 1.86 +/- 0.62 with the highest rates achieved in HH patients. An ER of 1.5
      was not reached in 37.9% of all procedures mainly concerning patients with a BV
      below 4,500 ml. In 12 newly diagnosed homozygous HH patients, the induction phase
      duration was medially 38.4 weeks (medially 10.5 procedures). During the
      maintenance treatment of HH, PV, and SE, the interval between TE procedures was
      medially 13.4 weeks. This mathematical model can help select the proper treatment
      modality for the individual patient. Especially for patients with a large BV and
      high achievable DeltaHct, TE appears to be more efficient than manual phlebotomy
      in RBC depletion thereby potentially reducing the numbers of procedures and
      expanding the interprocedural time period for HH, PV, and SE.

PMID- 24130065
TI  - Water mediation is essential to nucleation of beta-turn formation in peptide
      folding motifs.
AB  - Water-mediated bond formation: The structure of the peptide GPG-NH2 has been
      investigated in aqueous solution to understand the role of water in the formation
      of a beta-turn. Using a combination of neutron diffraction enhanced by isotopic
      substitution, NMR spectroscopy, and computer simulations, it was found that water
      is an essential component to initiate folding in solution. 

PMID- 24130066
TI  - Trends in seedling growth and carbon-use efficiency vary among broadleaf tree
      species along a latitudinal transect in eastern North America.
AB  - Factors constraining the geographic ranges of broadleaf tree species in eastern
      North America were examined in common gardens along a ~1500 km latitudinal
      transect travers in grange boundaries of four target species: trembling aspen
      (Populus tremuloides) and paper birch (Betula papyrifera) to the north vs.
      eastern cottonwood (Populus deltoides) and sweet gum (Liquidambar styraciflua) to
      the south. In 2006 and 2007, carbon-use efficiency (CUE), the proportion of
      assimilated carbon retained in biomass, was estimated for seedlings of the four
      species as the quotient of relative growth rate (RGR) and photosynthesis per unit
      tree mass (Atree ). In aspen and birch, CUE and RGR declined significantly with
      increasing growth temperature, which spanned 9  degrees C across gardens and
      years. The 37% (relative) CUE decrease from coolest to warmest garden correlated
      with increases in leaf nighttime respiration (Rleaf ) and the ratio of Rleaf to
      leaf photosynthesis (R%A ). For cottonwood and sweet gum, however, similar
      increases in Rleaf and R%A accompanied modest CUE declines, implying that
      processes other than Rleaf were responsible for species differences in CUE's
      temperature response. Our findings illustrate marked taxonomic variation, at
      least among young trees, in the thermal sensitivity of CUE, and point to
      potentially negative consequences of climate warming for the carbon balance,
      competitive ability, and persistence of two foundation species in northern
      temperate and boreal forests. 

PMID- 24130067
TI  - Racial differences in quality of life and employment outcomes in insured women
      with breast cancer.
AB  - PURPOSE: Prior studies indicate that racial disparities are not only present in
      cancer survival, but also in the quality of cancer survivorship. We estimated the
      effect of cancer and its treatment on two measures of survivorship quality as
      follows: health-related quality of life and employment and hours worked for
      initially employed and insured women newly diagnosed with breast cancer. METHODS:
      We collected employment data from 548 women from 2007 to 2011; 22 % were African
      American. The outcomes were responses to the SF-36, CES-D, employment, and change
      in weekly hours worked from pre-diagnosis to 2 and 9 months following treatment
      initiation. RESULTS: African-American women reported a 2.77 (0.94) and 1.96
      (0.92) higher score on the mental component summary score at the 2 and 9 month
      interviews, respectively. They also report fewer depression symptoms at the 2
      month interview, but were over half as likely to be employed as non-Hispanic
      white women (OR = 0.43; 95 % CI = 0.26 to 0.71). At the 9-month interview,
      African-American women had 2.33 (1.06) lower scores on the physical component
      summary score. CONCLUSIONS: Differences in health-related quality of life were
      small and, although statistically significant, were most likely clinically
      insignificant between African-American and non-Hispanic white women. Differences
      in employment were substantial, suggesting the need for future research to
      identify reasons for disparities and interventions to reduce the employment
      effects of breast cancer and its treatment on African-American women.
      IMPLICATIONS FOR CANCER SURVIVORS: African-American breast cancer survivors are
      more likely to stop working during the early phases of their treatment. These
      women and their treating physicians need to be aware of options to reduce work
      loss and take steps to minimize long-term employment consequences.

PMID- 24130068
TI  - Crystallographic characterization of a fully rotated, basic diiron dithiolate:
      model for the H(red) state?
AB  - A lucky break: A combination of steric pressure and electron asymmetry has
      provided the first example of a diiron dithiolate that is both rotated and basic.
      The present work establishes the feasibility of a hydride free rotated structure
      for the Hred state of the enzyme. 

PMID- 24130069
TI  - Gene-silencing antisense oligomers inhibit acinetobacter growth in vitro and in
      vivo.
AB  - BACKGROUND: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs)
      are synthetic DNA/RNA analogues that silence expression of specific genes. We
      studied whether PPMOs targeted to essential genes in Acinetobacter lwoffii and
      Acinetobacter baumannii are active in vitro and in vivo. METHODS: PPMOs were
      evaluated in vitro using minimum inhibitory concentration (MIC) and viability
      assays, and in vivo using murine pulmonary infection models with intranasal PPMO
      treatment. RESULTS: MICs of PPMOs ranged from 0.1 to 64 uM (approximately 0.6-38
      ug/mL). The most effective PPMO tested was (RXR)4-AcpP, which is targeted to
      acpP. (RXR)4-AcpP reduced viability of A. lwoffii and A. baumannii by >10(3)
      colony-forming units/mL at 5-8 times MIC. Mice treated with >=0.25 mg/kg of
      (RXR)4-AcpP survived longer and had less inflammation and bacterial lung burden
      than mice treated with a scrambled-sequence PPMO or phosphate-buffered saline.
      Treatment could be delayed after infection and still increase survival.
      CONCLUSIONS: PPMOs targeted to essential genes of A. lwoffii and A. baumannii
      were bactericidal and had MICs in a clinically relevant range. (RXR)4-AcpP
      increased survival of mice infected with A. lwoffii or A. baumannii, even when
      initial treatment was delayed after infection. PPMOs could be a viable
      therapeutic approach in dealing with multidrug-resistant Acinetobacter species.

PMID- 24130070
TI  - Au dotted magnetic network nanostructure and its application for on-site
      monitoring femtomolar level pesticide.
AB  - A novel magnetically responsive and surface-enhanced Raman spectroscopy (SERS)
      active nanocomposite is designed and prepared by direct grafting of Au
      nanoparticles onto the surface of magnetic network nanostructure (MNN) with the
      help of a nontoxic and environmentally friendly reagent of inositol
      hexakisphosphate shortly named as IP6. The presence of IP6 as a stabilizer and a
      bridging agent could weave Fe3O4 nanoparticles (NPs) into magnetic network
      nanostructure, which is easily dotted with Au nanoparticles (Au NPs). It has been
      shown firstly that the huge Raman enhancement of Au-MNN is reached by an external
      magnetic collection. Au-MNN presenting the large surface and high detection
      sensitivity enables it to exhibit multifunctional applications involving
      sufficient adsorption of dissolved chemical species for enrichment, separation,
      as well as a Raman amplifier for the analysis of trace pesticide residues at
      femtomolar level by a portable Raman spectrometer. Therefore, such
      multifunctional nanocomposites can be developed as a smart and promising
      nanosystem that integrates SERS approach with an easy assay for concentration by
      an external magnet for the effective on-site assessments of agricultural and
      environmental safety.

PMID- 24130071
TI  - Epigenetic inactivation of microRNA-34b/c predicts poor disease-free survival in
      early-stage lung adenocarcinoma.
AB  - PURPOSE: The microRNA-34b/c (miR-34b/c) is considered a tumor suppressor in
      different tumor types and a transcriptional target of TP53. The main objectives
      of this study were to investigate the clinical implications of miR-34b/c
      methylation in patients with early-stage lung adenocarcinoma and to determine the
      functional role of miR-34b/c re-expression in lung adenocarcinoma cell lines.
      EXPERIMENTAL DESIGN: Aberrant methylation and expression of miR-34b/c were
      assessed in 15 lung adenocarcinoma cell lines and a cohort of 140 early-stage
      lung adenocarcinoma. Lung adenocarcinoma cell lines were transfected with miR
      34b/c and the effects upon cell proliferation, migration, invasion, and apoptosis
      were investigated. RESULTS: Aberrant methylation of miR-34b/c was detected in 6
      (40%) of 15 lung adenocarcinoma cell lines and 64 of 140 (46%) primary lung
      adenocarcinoma. Expression of miR-34b/c was significantly reduced in all
      methylated cell lines and primary tumors, especially with TP53 mutations.
      Patients with increased miR-34b/c methylation had significantly shorter disease
      free and overall survival as compared to patients with unmethylated or low level
      of miR-34b/c methylation. Ectopic expression of miR-34b/c in lung adenocarcinoma
      cell lines decreased cell proliferation, migration, and invasion. CONCLUSIONS:
      Epigenetic inactivation of miR-34b/c by DNA methylation has independent
      prognostic value in patients with early-stage lung adenocarcinoma. Reexpression
      of miR-34b/c leads to a less aggressive phenotype in lung adenocarcinoma cell
      lines.

PMID- 24130074
TI  - Effects of long-term storage on Mal d 1 content of four apple cultivars with
      initial low Mal d 1 content.
AB  - BACKGROUND: Up to 6.6% of adults and 11.5% of children aged between 0 and 6 years
      are reporting a perceived fruit allergy. In the last group 8.5% perceived
      reactions against apple. To keep allergic reactions as low as possible and to
      make apple consumption more tolerable for patients allergic to apple, the Mal d 1
      content of four apple cultivars ('Boskoop', 'Elise', 'Pinova', 'Santana' and
      'Topaz') were analyzed, to identify apple cultivars with only a low Mal d 1
      content. Further, the development of Mal d 1 content of low-allergenic cultivars
      should be investigated during long-term storage. RESULTS: The lowest Mal d 1
      content was measured for fruits of the cultivar 'Santana' at harvest, followed by
      'Pinova' and 'Elise' after storage without 1-MCP. Nearly all fruits treated with
      1-MCP had a significantly lower Mal d 1 content than fruits without 1-MCP, except
      for 'Boskoop' fruits after 44 weeks of storage. Apple cultivars with a low Mal d
      1 content are not a cross of 'Golden Delicious' with another cultivar, with the
      exception of 'Pinova' which is a cultivar from the so-called 'Pi-series', which
      have a moderate resistance to scab and mildew. First experiments on tomatoes and
      peanuts have shown a reduction of allergic proteins in older and child
      generations after transfer of RNA. This reduction is probably based on an
      alteration of gene expression regulating the synthesis of allergic proteins,
      leading to changes in protein composition in the fruit. CONCLUSION: Individuals
      allergic to apple should choose the described cultivars with relative low Mal d 1
      content. If breeders want to breed cultivars with low allergy, they should avoid
      crossings with 'Golden Delicious'.

PMID- 24130073
TI  - The effect of VEGF-targeted therapy on biomarker expression in sequential tissue
      from patients with metastatic clear cell renal cancer.
AB  - PURPOSE: To investigate how biologically relevant markers change in response to
      antiangiogenic therapy in metastatic clear cell renal cancer (mRCC) and correlate
      these changes with outcome. EXPERIMENTAL DESIGN: The study used sequential tumor
      tissue and functional imaging (taken at baseline and 12-16 weeks) obtained from
      three similar phase II studies. All three studies investigated the role of VEGF
      tyrosine kinase inhibitors (TKI) before planned nephrectomy in untreated mRCC (n
      = 85). The effect of targeted therapy on ten biomarkers was measured from
      sequential tissue. Comparative genomic hybridization (CGH) array and DNA
      methylation profiling (MethylCap-seq) was performed in matched frozen pairs.
      Biomarker expression was correlated with early progression (progression as best
      response) and delayed progression (between 12-16 weeks). RESULTS: VEGF TKI
      treatment caused a significant reduction in vessel density (CD31), phospho-S6K
      expression, PDL-1 expression, and FOXP3 expression (P < 0.05 for each). It also
      caused a significant increase in cytoplasmic FGF-2, MET receptor expression in
      vessels, Fuhrman tumor grade, and Ki-67 (P < 0.05 for each). Higher levels of Ki
      67 and CD31 were associated with delayed progression (P < 0.05). Multiple samples
      (n = 5) from the same tumor showed marked heterogeneity of tumor grade, which
      increased significantly with treatment. Array CGH showed extensive intrapatient
      variability, which did not occur in DNA methylation analysis. CONCLUSION: TKI
      treatment is associated with dynamic changes in relevant biomarkers, despite
      significant heterogeneity in chromosomal and protein, but not epigenetic
      expression. Changes to Ki-67 expression and tumor grade indicate that treatment
      is associated with an increase in the aggressive phenotype of the tumor.

PMID- 24130072
TI  - A comparative analysis of prognostic factor models for follicular lymphoma based
      on a phase III trial of CHOP-rituximab versus CHOP + 131iodine--tositumomab.
AB  - PURPOSE: There is currently no consensus on optimal frontline therapy for
      patients with follicular lymphoma. We analyzed a phase III randomized intergroup
      trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine
      prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131
      tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more
      from one treatment or the other, and to compare three prognostic models.
      EXPERIMENTAL DESIGN: We conducted univariate and multivariate Cox regression
      analyses of 532 patients enrolled on this trial and compared the prognostic value
      of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and
      LDH + beta2M (lactate dehydrogenase + beta2-microglobulin) models. RESULTS:
      Outcomes were excellent, but not statistically different between the two study
      arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP
      RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP
      RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor
      found to potentially predict the impact of treatment was serum beta2M; among
      patients with normal beta2M, CHOP-RIT patients had better PFS compared with CHOP
      R patients, whereas among patients with high serum beta2M, PFS by arm was similar
      (interaction P value = 0.02). CONCLUSIONS: All three prognostic models (FLIPI,
      FLIPI2, and LDH + beta2M) predicted both PFS and OS well, though the LDH + beta2M
      model is easiest to apply and identified an especially poor risk subset. In an
      exploratory analysis using the latter model, there was a statistically
      significant trend suggesting that low-risk patients had superior observed PFS if
      treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R.

PMID- 24130075
TI  - Long-acting reversible contraception: a review in special populations.
AB  - Almost half of the pregnancies in the United States are unintended. Currently
      available contraceptive methods are highly efficacious, but the most commonly
      used methods rely on patients for appropriate use. There has been a push to
      advocate for long-acting reversible contraceptives (LARCs) as first-line methods
      because they are placed by medical professionals and are the most effective form
      of reversible contraception available. There are four LARCs currently available
      in the United States: the Copper T intrauterine device, two forms of the
      levonorgestrel intrauterine system, and the etonogestrel subdermal implant. Once
      inserted, they can be left in place for 3-10 years, depending on the device. Some
      of these devices have been available for a number of years, but their use is
      limited in the United States due to controversies and misconceptions. A MEDLINE
      search from 1990-2012 was conducted to identify articles describing the use of
      LARCs in populations with limited data, including postpartum women, adolescents
      and nulliparous women, and women with sexually transmitted infections, including
      human immunodeficiency virus (HIV). Health care provider safety concerns
      surrounding intrauterine device (IUD) expulsions and infection are issues for use
      in adolescents and nulliparous women. Concern regarding IUD expulsion in the
      postpartum population questions the benefit of immediate versus delayed
      insertion, and the progestin effect in the levonorgestrel IUD and etonogestrel
      implant is of theoretic concern for breastfeeding women. In women with HIV,
      concerns have been raised about increased viral shedding with the IUD and drug
      interactions with the progestin methods. Many misconceptions surrounding LARCs
      are unfounded, but individual risk factors may leave LARC users at risk of
      unintended pregnancy if not addressed properly. 

PMID- 24130076
TI  - Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic
      fibroblast growth factor.
AB  - Anastomotic leakage is a common complication of intestinal surgery. In an attempt
      to resolve this issue, a promising approach is enhancement of anastomotic wound
      healing. A method for controlled release of basic fibroblast growth factor (bFGF)
      using a gelatin hydrogel was developed with the objective of investigating the
      effects of this technology on intestinal anastomotic healing. The small intestine
      of Wistar rats was cut, end-to-end anastomosis was performed and rats were
      divided into three groups: bFGF group (anastomosis wrapped with a hydrogel sheet
      incorporating bFGF), PBS group (wrapped with a sheet incorporating phosphate
      buffered saline solution) and NT group (no additional treatment). Degradation
      profiles of gelatin hydrogels in vivo and histological examinations were
      performed using gelatin hydrogels with various water contents and bFGF
      concentrations to define the optimal bFGF dose and hydrogel biodegradability. The
      anastomotic wound healing process was evaluated by histological examinations,
      adhesion-related score and bursting pressure. The optimal water content of the
      hydrogel and bFGF dose was determined as 96% and 30 ug per sheet, respectively.
      Application of bFGF significantly enhanced neovascularization, fibroblast
      infiltration and collagen production around the anastomotic site when compared
      with the other groups. Bursting pressure was significantly increased in the bFGF
      group. No significant difference was observed in the adhesion-related score among
      the groups and no anastomotic obstruction and leakage were observed. Therefore
      controlled release of bFGF enhanced healing of an intestinal anastomosis during
      the early postoperative period and is a promising method to suppress anastomotic
      leakage. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24130077
TI  - Hierarchical hydrogen bonds directed multi-functional carbon nanotube-based
      supramolecular hydrogels.
AB  - Supramolecular hydrogels (SMHs) are three-dimensional networks filled with a
      large amount of water. The crosslinking force in the 3D network is always
      constructed by relatively weak and dynamic non-covalent interactions, and thus
      SMHs usually possess extremely high susceptibility to external environment and
      can show extraordinary stimuli-responsive, self-healing or other attractive
      properties. However, the overall crosslinking force in hydrogel networks is
      difficult to flexibly modulate, and this leads to limited functions of the SMHs.
      In this regard, hierarchical hydrogen bonds, that is, the mixture of relatively
      strong and relatively weak hydrogen bonds, are used herein as crosslinking force
      for the hydrogel preparation. The ratio of strong and weak hydrogen bonds can be
      finely tuned to tailor the properties of resultant gels. Thus, by delicate
      manipulation of the overall crosslinking force in the system, a hydrogel with
      multiple (thermal, pH and NIR light) responsiveness, autonomous self-healing
      property and interesting temperature dependent, reversible adhesion behavior is
      obtained. This kind of hierarchical hydrogen bond manipulation is proved to be a
      general method for multiple-functionality hydrogel preparation, and the resultant
      material shows potential for a range of applications. 

PMID- 24130078
TI  - Comparison of Bayesian methods for flexible modeling of spatial risk surfaces in
      disease mapping.
AB  - Bayesian hierarchical models usually model the risk surface on the same arbitrary
      geographical units for all data sources. Poisson/gamma random field models
      overcome this restriction as the underlying risk surface can be specified
      independently to the resolution of the data. Moreover, covariates may be
      considered as either excess or relative risk factors. We compare the performance
      of the Poisson/gamma random field model to the Markov random field (MRF)-based
      ecologic regression model and the Bayesian Detection of Clusters and
      Discontinuities (BDCD) model, in both a simulation study and a real data example.
      We find the BDCD model to have advantages in situations dominated by abruptly
      changing risk while the Poisson/gamma random field model convinces by its
      flexibility in the estimation of random field structures and by its flexibility
      incorporating covariates. The MRF-based ecologic regression model is inferior.
      WinBUGS code for Poisson/gamma random field models is provided. 

PMID- 24130079
TI  - Concussive brain injury in the military: September 2001 to the present.
AB  - Since the terrorist attacks of September 11, 2001, 1,348,405 citizens have been
      deployed to combat in Operation Iraqi Freedom (OIF), Operation New Dawn in Iraq,
      and Operation Enduring Freedom in Afghanistan (OEF). During this same period
      266,810 (20%) of these individuals have been diagnosed with a traumatic brain
      injury (TBI). The majority of these were Army soldiers, with 155,282 (58%)
      receiving the diagnosis. Mild TBI comprised 82% of the total, with the remainder
      being moderate to severe. Over this same period the Department of Defense (DoD)
      has invested $374.9 million to enhance access and quality of care services,
      including 57 TBI treatment centers in the combat theater and throughout the U.S.
      The Army's medical research division, the Medical Research and Material Command
      (MRMC), has invested an additional $700 million to TBI research during this time.
      The effort has faced a number of challenges, including limited human subject
      basic and translational research, limited epidemiological data on combat-related
      injuries, limited capacity and standards for data acquisition, and a lack of
      standardized evidenced-based protocols for treatment. All these areas have
      undergone significant growth and development, leading to the comprehensive system
      of care present today. A further challenge in this patient population has been
      the clinical co-morbidity of TBI, post-traumatic stress disorder, and chronic
      pain syndrome. The Army and the DoD have created treatment programs that are
      interdisciplinary in clinical approach, targeting particular neuropsychological
      domains of dysfunction rather than diagnostic category or etiology of injury.
      This article presents the history of this effort, the challenges to accurate and
      adequate diagnosis and care that remain, and the future of brain injury clinical
      and research efforts in the military.

PMID- 24130080
TI  - Tracheoesophageal puncture with immediate prosthesis placement.

PMID- 24130081
TI  - Changes in insulin sensitivity in response to different modalities of exercise: a
      review of the evidence.
AB  - Type 2 diabetes is an increasingly prevalent condition with complications
      including blindness and kidney failure. Evidence suggests that type 2 diabetes is
      associated with a sedentary lifestyle, with physical activity demonstrated to
      increase glucose uptake and improve glycaemic control. Proposed mechanisms for
      these effects include the maintenance and improvement of insulin sensitivity via
      increased glucose transporter type four production. The optimal mode, frequency,
      intensity and duration of exercise for the improvement of insulin sensitivity are
      however yet to be identified. We review the evidence from 34 published studies
      addressing the effects on glycaemic control and insulin sensitivity of aerobic
      exercise, resistance training and both combined. Effect sizes and confidence
      intervals are reported for each intervention and meta-analysis presented. The
      quality of the evidence is tentatively graded, and recommendations for best
      practice proposed.

PMID- 24130083
TI  - Abstracts of the IPOS 15th World Congress of Psycho-Oncology. November 4-8, 2013.
      Rotterdam, The Netherlands.

PMID- 24130084
TI  - Climatic and technological ceilings for Chinese rice stagnation based on yield
      gaps and yield trend pattern analysis.
AB  - Climatic or technological ceilings could cause yield stagnation. Thus,
      identifying the principal reasons for yield stagnation within the context of the
      local climate and socio-economic conditions are essential for informing regional
      agricultural policies. In this study, we identified the climatic and
      technological ceilings for seven rice-production regions in China based on yield
      gaps and on a yield trend pattern analysis for the period 1980-2010. The results
      indicate that 54.9% of the counties sampled experienced yield stagnation since
      the 1980. The potential yield ceilings in northern and eastern China decreased to
      a greater extent than in other regions due to the accompanying climate effects of
      increases in temperature and decreases in radiation. This may be associated with
      yield stagnation and halt occurring in approximately 49.8-57.0% of the sampled
      counties in these areas. South-western China exhibited a promising scope for
      yield improvement, showing the greatest yield gap (30.6%), whereas the yields
      were stagnant in 58.4% of the sampled counties. This finding suggests that
      efforts to overcome the technological ceiling must be given priority so that the
      available exploitable yield gap can be achieved. North-eastern China, however,
      represents a noteworthy exception. In the north-central area of this region,
      climate change has increased the yield potential ceiling, and this increase has
      been accompanied by the most rapid increase in actual yield: 1.02 ton ha(-1) per
      decade. Therefore, north-eastern China shows a great potential for rice
      production, which is favoured by the current climate conditions and available
      technology level. Additional environmentally friendly economic incentives might
      be considered in this region. 

PMID- 24130082
TI  - Role of cell-matrix interactions on VIC phenotype and tissue deposition in 3D PEG
      hydrogels.
AB  - Valvular interstitial cells (VICs) respond to 3D matrix interactions in a complex
      manner, but understanding these effects on VIC function better is important for
      applications ranging from valve tissue engineering to studying valve disease.
      Here, we encapsulated VICs in poly(ethylene glycol) (PEG) hydrogels modified with
      three different adhesive ligands, derived from fibronectin (RGDS), elastin
      (VGVAPG) and collagen-1 (P15). By day 14, VICs became significantly more
      elongated in RGDS-containing gels compared to VGVAPG or P15. This difference in
      cell morphology appeared to correlate with global matrix metalloproteinase (MMP)
      activity, as VICs encapsulated in RGDS-functionalized hydrogels secreted higher
      levels of active MMP at day 2. VIC activation to a myofibroblast phenotype was
      also characterized by staining for alpha-smooth muscle actin (alphaSMA) at day
      14. The percentage of alphaSMA+ VICs in the VGVAPG gels was the highest (56%)
      compared to RGDS (33%) or P15 (38%) gels. Matrix deposition and composition were
      also characterized at days 14 and 42 and found to depend on the initial hydrogel
      composition. All gel formulations had similar levels of collagen, elastin and
      chondroitin sulphate deposited as the porcine aortic valve. However, the
      composition of collagen deposited by VICs in VGVAPG-functionalized gels had a
      significantly higher collagen-X:collagen-1 ratio, which is associated with
      stenotic valves. Taken together, these data suggest that peptide-functionalized
      PEG hydrogels are a useful system for culturing VICs three-dimensionally and,
      with the ability to systematically alter biochemical and biophysical properties,
      this platform may prove useful in manipulating VIC function for valve
      regeneration. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24130085
TI  - Simulating microwave chemistry in a resistance-heated autoclave made of
      semiconducting silicon carbide ceramic.

PMID- 24130086
TI  - Phase I study of clofarabine in adult patients with acute myeloid leukemia in
      Japan.
AB  - OBJECTIVE: There are limited treatment options for relapsed/refractory acute
      myeloid leukemia patients or previously untreated elderly (>=60 years) patients
      with acute myeloid leukemia. In Phase II studies from the USA and Europe, single
      agent clofarabine demonstrated activity and acceptable toxicity in elderly
      patients with previously untreated acute myeloid leukemia. This Phase I,
      multicenter study assessed the maximum-tolerated dose, safety, pharmacokinetics
      and efficacy of clofarabine in Japanese adults with acute myeloid leukemia.
      METHODS: Intravenous clofarabine (20, 30 and 40 mg/m(2)/day) was administered for
      5 days to Japanese adult patients with relapsed or refractory acute myeloid
      leukemia or elderly patients with newly diagnosed acute myeloid leukemia.
      RESULTS: Fourteen patients, median age of 67.5 (59-72) years, were enrolled in
      this study. Eleven out of 14 patients had relapsed/refractory acute myeloid
      leukemia. Three patients received clofarabine at 20 mg/m(2), six at 30 mg/m(2)
      and five at 40 mg/m(2). Frequently reported treatment-related adverse events
      included thrombocytopenia (100%), anemia (93%), neutropenia (86%), nausea (86%),
      alanine aminotransferase increase (71%), headache (71%) and febrile neutropenia
      (57%). Three patients experienced reversible dose-limiting toxicities; two had
      increased alanine aminotransferase with 30 and 40 mg/m(2) and one had Grade 3
      elevation of serum amylase with 40 mg/m(2). The maximum-tolerated dose was 30
      mg/m(2)/day. Cmax and exposure area under the curve0-24h increased with
      increasing dose and were proportional to dose through the tested dose range.
      Among the 14 assessable patients, four (29%) achieved complete remission and two
      (14%) complete remission without platelet recovery. The overall remission rate
      was 43%. CONCLUSIONS: These results demonstrate safety and preliminary, promising
      activity of clofarabine in Japanese patients with acute myeloid leukemia. Further
      investigation is warranted.

PMID- 24130087
TI  - Novel application of acetazolamide to reduce cerebrospinal fluid production in
      patients undergoing thoracoabdominal aortic surgery.
AB  - OBJECTIVES: Paraplegia is a rare but devastating complication, which may follow
      thoracoabdominal aortic surgery. Many adjuncts have been developed to reduce this
      risk including cerebrospinal fluid (CSF) drainage. Acetazolamide (carbonic
      anhydrase inhibitor) is a drug used to counteract mountain sickness and one of
      its effects is to reduce CSF production. Here, we report its first postoperative
      application in thoracoabdominal surgery with the aim of reducing cerebrospinal
      cord perfusion pressure and reducing risk of paraplegia. METHODS: We
      retrospectively reviewed 6 patients who have been treated with this drug between
      2011 and 2012 who were undergoing thoracoabdominal aortic surgery. Our
      indications were decided to include: (i) patients in whom a spinal drain could
      not be positioned; (ii) patients with blood-stained CSF; (iii) patients in whom
      the volume of CSF drained was outside guidelines; (iv) patients in whom CSF
      pressure was elevated; (v) patients with excessive vasopressor usage and (vi)
      patients with postoperative neurological dysfunction as measured by motor-evoked
      potentials or clinical examination. All were given 500 mg intravenous
      acetazolamide, not more than eight hourly, for a duration dependent on response.
      RESULTS: In the 6 patients, 2 received a single dose of the drug and responded by
      an immediate drop in intracranial pressure (ICP) pressure. Of the 4 who received
      multiple doses of the drug, 1 had an immediate decline in ICP after each of the
      first six doses, while 3 had no discernable response. CONCLUSIONS: This is the
      first report of the efficacy of acetazolamide in reducing CSF production and
      lowering ICP during thoracoabdominal aortic surgery. We believe that its use will
      be beneficial in the 6 patient groups described. Our experience suggests there
      are 'responders' and 'non-responders', the characteristics of whom are yet to be
      defined. Its efficacy in reducing not just CSF volume and ICP but also clinically
      relevant morbidity such as paraplegia, is the subject of a planned randomized
      controlled trial. This report serves to raise awareness of the possible efficacy
      of this drug when normal management strategies are limited or exhausted.

PMID- 24130088
TI  - Long-term follow-up after autologous skeletal myoblast transplantation in
      ischaemic heart disease.
AB  - OBJECTIVES: Short-term follow-up after autologous skeletal myoblasts (ASM)
      transplantation (Tx) (Myoblast Autologous Grafting in Ischaemic Cardiomyopathy
      (MAGIC) Phase II Study) for the treatment of ischaemic cardiomyopathy revealed
      improved left ventricular (LV) remodelling. Our study reports the longest long
      term worldwide follow-up of a single-centre cohort, focusing on the safety and
      efficacy of ASM-Tx. METHODS: The multicentre MAGIC Phase II Study involved 120
      patients and was conducted between 2004 and 2006. Out of the 120 patients
      involved in the entire study, the cohort treated at our institution contained 7
      patients only. These 7 patients received ASM-Tx (injection volume: 400 million
      cells, n = 2 low dosage; 800 million cells, n = 2 high dosage) or placebo (n = 3)
      injections, in addition to coronary artery bypass grafting (CABG). After closure
      of the MAGIC registry, we conducted a long-term follow-up for our 7-patient
      cohort. The mean follow-up was 72.0 +/- 5.3 months. The follow-up was complete
      for echo data, implanted cardioverter defibrillator (ICD) report, clinical
      investigation and New York Heart Association (NYHA) class. RESULTS: At final
      follow-up, all the patients were alive, and 5 were in NYHA class 1 or 2. There
      were 6 hospitalizations for congestive heart failure during the follow-up (1
      patient from each group). One patient (placebo group) was treated twice for
      ventricular fibrillation by the ICD. The LV ejection fraction remained stable in
      all the three groups (31.1 +/- 3.9% preoperative vs 29.4 +/- 4.4% at final follow
      up). The LV volumes were reduced in the high-dosage group, remained unchanged in
      the low-dosage group and deteriorated in the placebo group. CONCLUSIONS: Our long
      term data confirm the findings of the MAGIC study. The LV function did not
      improve, but the long-term LV volumes in the high-dosage group were reduced.
      During the follow-up, there were also no additional arrhythmogenic incidences.
      Our data could imply that CABG in combination with ASM-Tx is safe and has
      beneficial therapeutic effects in the long-term. However, due to the small
      patient number, the clinical impact is limited.

PMID- 24130089
TI  - Comparison of local tissue damage: monopolar cutter versus Nd:YAG laser for lung
      parenchyma resection. An experimental study.
AB  - OBJECTIVES: Lung metastases are non-anatomically resected while sparing as much
      parenchyma as possible. For this purpose, a few surgeons use the Nd:YAG Laser
      LIMAX 120, whereas the majority of surgeons use a monopolar cutter like the
      MAXIUM. The aim of this experimental study was to investigate which instrument
      causes less lung-tissue damage at the same power output. METHODS: These
      experiments were conducted on left lungs (n = 6) taken from freshly slaughtered
      pigs. The laser and the monopolar cutter were fixed in a hydraulic mover. The
      laser was focused at a distance of 3 cm to the lung tissue and the monopolar
      cutter was fixed in pressure-free contact with the lung surface. Both instruments
      were manoeuvred at a speed of 5, 10 and 20 mm/s in a straight line at an output
      of 100 watts over the lung surface. The lung lesions that ensued were then
      examined macro- and microscopically. The same procedures were repeated at a
      distance of 1 cm creating parallel lesions in order to analyse the lung tissue in
      between the lesions for thermal damage. In addition, two implanted capsules in
      the lung tissue simulating a lung nodule were resected with either the laser or
      the monopolar cutter. The resection surfaces were then examined by magnetic
      resonance imaging and histology for tissue damage. Finally, we created a 2-cm
      wide mark on the lung surface to test the resection capacity of both instruments
      within 1 min. RESULTS: The laser created sharply delineated lesions with a
      vaporization and coagulation zone without thermal damage of the surrounding lung
      tissue. With lowering the working speed, each zone was extended. At a working
      speed of 10 mm/s, the mean vaporization depth using the laser was 1.74 +/- 0.1 mm
      and the mean coagulation depth was 1.55 +/- 0.09 mm. At the same working speed,
      the monopolar cutter demonstrated a greater cutting effect (mean vaporization
      depth 2.7 +/- 0.11 mm; P < 0.001) without leaving much coagulation on the
      resection surface (mean coagulation depth 1.25 +/- 0.1 mm; P = 0.002). In
      contrast to the laser, the monopolar cutter caused thermal damage of the adjacent
      lung tissue. The adjacent tissue injury was detected in histological examination
      as well as in the MRI findings. Adjacent lung tissue after lung metastasectomy
      using the monopolar cutter was hyper-intensive in T2-weighted MR imaging,
      indicating a severe tissue damage. No significant changes in signal intensity
      were observed in T2-weighted imaging of the adjacent lung tissue after using the
      laser for lung resection. One minute of laser applied at a 100-watt output
      penetrated a lung surface area of 3.8 +/- 0.4 cm(2) compared with 4.8 +/- 0.6
      cm(2) of surface after application of the monopolar cutter (P = 0.001).
      CONCLUSIONS: The monopolar cutter possesses indeed a greater cutting capacity
      than the laser, but it also causes more adjacent tissue injury. Thus, laser
      resection might be preferred for lung metastasectomy.

PMID- 24130090
TI  - Bridging the gap in the micellar transformation from cylinders to vesicles.
AB  - The micelles of polystyrene-block-poly(acrylic acid) (PS154-b-PAA49) are made to
      transform slowly in mixed solvent, allowing continual trapping of the various
      intermediates. During the transformation from cylindrical to vesicular micelles,
      it appears that a section of the cylinder first flattens to give a lamellar
      section, which then depresses to give a bowl-like moiety, before finally
      converting to a fully enclosed vesicle. Most part of this transformation involves
      the "flow" of polymer domains without mingling of the hydrophobic and hydrophilic
      domains. On the bases of the literature and the observation in this work, it is
      proposed that the reduction of surface-to-volume ratio provides the thermodynamic
      driving force for the cylinder-to-vesicle transformation, whereas molecular
      reorganization within the polymer domains creates the kinetic barrier. From the
      point of view of molecular interactions, the "flow" of polymer domain involves a
      low barrier, whereas the merging of two micelles, the severing of cylindrical
      micelles, and the closing of partial vesicles encounter high barriers. Moreover,
      the kinetic barrier is reduced when PSPAA containing shorter PAA blocks is used,
      or when the PAA block are protonated. This mechanistic proposal explains the
      kinetically controlled transformation pathway and structural features of the
      observed intermediates.

PMID- 24130091
TI  - Comparative expression of thioredoxin-1 in uterine leiomyomas and myometrium.
AB  - Uterine leiomyomas are benign tumors that develop from smooth muscle cells
      (SMCs). The reactive oxygen species (ROS) have been shown to be involved in the
      signaling pathways that stimulate proliferation of a variety of cell types.
      Thioredoxin-1 (TRX-1) is a redox-regulating protein, which is overexpressed in
      various tumors. In the present study, we investigated the expressions of TRX-1
      and its related molecules in uterine leiomyomas and matched adjacent myometrium.
      Our results showed the expression of TRX-1 was increased in leiomyomas compared
      with the matched adjacent myometrium by quantitative RT-PCR and western blotting.
      FOXO3A expression was increased in leiomyomas compared with myometrium by western
      blotting. The mRNA levels of hypoxia-inducible factor-1alpha, cyclooxygenase-2
      and cyclin D1 were increased in leiomyomas compared with the adjacent myometrium.
      The mRNA level of (thioredoxin-1-binding protein) TBP-2 in leiomyomas was not
      altered when compared with the matched adjacent myometrium. These results suggest
      that TRX-1 and some of its related molecules are associated with the pathogenesis
      of uterine leiomyomas. The identification of TRX-1 signaling pathways leading to
      cell proliferation points to another potential therapeutic target for treatment
      and/or prevention of uterine leiomyomas. 

PMID- 24130092
TI  - Voice outcomes following reconstruction of laryngopharyngectomy defects using the
      radial forearm free flap and the anterolateral thigh free flap.
AB  - OBJECTIVES/HYPOTHESIS: Patients undergoing laryngopharyngectomy with extensive
      pharyngeal mucosal resection or those failing chemoradiation protocols are
      commonly reconstructed using free tissue transfer. Radial forearm free flaps
      (RFFFs) and anterolateral thigh free flaps (ALTs) are two of the most commonly
      used free flaps for laryngopharyngectomy reconstruction. It has been suggested
      that alaryngeal tracheoesophageal prosthesis (TEP) speech outcomes in patients
      undergoing ALT reconstruction may be inferior due to the possibly bulkier
      neopharynx. We report the results of patients treated with ALT and RFFF with
      regard to postoperative TEP voice outcomes. STUDY DESIGN: Retrospective cohort
      study. METHODS: We identified 42 consecutive patients who were treated with total
      laryngopharyngectomy and free flap reconstruction utilizing either RFFFs (20
      patients) or ALTs (22 patients) between April 2001 and August 2010. Evaluations
      with statistical analysis of standard TEP speech outcome measures (maximal
      sustained phonation, fluent count, syllable count) and qualitative variables were
      conducted. RESULTS: Patient demographics were similar between the RFFF and ALT
      groups, and 95% and 91% of RFFF and ALT patients received radiation therapy,
      respectively. Subjective voice quality did not significantly differ between the
      groups. Differences in outcomes of intelligibility, maximal sustained phonation
      time, maximum number of syllables, and fluent count, as evaluated by a single
      speech pathologist, were not statistically significant between RFFF and ALT
      patients. There was no difference in postoperative complications. CONCLUSIONS:
      These data indicate that reconstruction of laryngopharyngectomy defects using
      either the ALT or RFFF technique can produce similarly acceptable TEP voice
      results. LEVEL OF EVIDENCE: 2b.

PMID- 24130093
TI  - Human immature dental pulp stem cells (hIDPSCs), their application to cell
      therapy and bioengineering: an analysis by systematic revision of the last decade
      of literature.
AB  - During recent years, attention has been given to the potential of therapeutic
      approaches using stem cells obtained from dental pulp tissue. The aim of this
      study, therefore, was to give an overview of the papers produced during the last
      10 years that have described the use of stem cells obtained from human deciduous
      teeth in cell therapy or bioengineering. The PubMed database was investigated
      from January 2002 until July 2011 and the papers published during this period
      were analyzed according to criteria previously established, using the methodology
      of systematic review. The measurements were done using "stem cell" as the primary
      keyword, and "human deciduous teeth dental pulp cell" and "human exfoliated
      deciduous teeth" as the secondary keywords. Four hundred and seventy-five papers
      were found. The first screening resulted in 276 papers, from which 84 papers were
      selected. However, only 11 of them attained the aim proposed in our approach.
      There were few scientific studies related to direct therapeutic application using
      stem cells of human deciduous teeth and none of them had been applied to humans.
      However, the results indicated important and promising applications of the pulp
      stem-cells in cell therapy and bioengineering as demonstrated by studies in
      animal models of muscular dystrophy, Parkison's disease, and lupus erythematosus.

PMID- 24130094
TI  - Refining perforator selection for deep inferior epigastric perforator flap: the
      impact of the dominant venous perforator.
AB  - INTRODUCTION: This article aims to investigate the critical role of the venous
      perforator in the decision-making process of choosing the best suitable
      perforator-complex in a deep inferior epigastric perforator (DIEP) flap. METHODS:
      Forty consecutive DIEP breast reconstructions were pre-operatively evaluated by
      CT-Angiography to identify the dominant and centrally located abdominal wall
      perforators. The CTA results were used as a guide to conduct a Color-Duplex
      Ultrasound examination that was mainly focused on investigating the accompanying
      venous-perforator. In group-A (n = 20) perforator-complex selection was based on
      the size of the arterial-perforator, whilst in group-B (n = 20) it was based on
      the size of the venous-perforator. RESULTS: All single perforator-complex DIEP
      flaps survived. No significant differences were recorded concerning the size of
      arterial-perforator between the two groups; however the size of venous-perforator
      was significantly larger in group-B (P < 0.05). In group-A, four flaps showed
      vascular compromise intraoperative that was salvaged by flap supercharge with the
      superficial inferior epigastric system. In contrast, in group-B, all flaps were
      re-vascularized uneventfully (P < 0.05). Physical examination revealed a palpable
      mass in one patient and ultrasound investigation added three cases with a firm
      area of scar tissue in group-A, but no fat necrosis was detected in group-B (P <
      0.05). CONCLUSIONS: The CTA-guided duplex ultrasonography could direct the
      perforator-complex selection according to the size of the venous-perforator, and
      may reduce the intraoperative problems and the incidence of fat necrosis.

PMID- 24130095
TI  - Plant responses to elevated temperatures: a field study on phenological
      sensitivity and fitness responses to simulated climate warming.
AB  - Significant changes in plant phenology have been observed in response to
      increases in mean global temperatures. There are concerns that accelerated
      phenologies can negatively impact plant populations. However, the fitness
      consequence of changes in phenology in response to elevated temperature is not
      well understood, particularly under field conditions. We address this issue by
      exposing a set of recombinant inbred lines of Arabidopsis thaliana to a simulated
      global warming treatment in the field. We find that plants exposed to elevated
      temperatures flower earlier, as predicted by photothermal models. However,
      contrary to life-history trade-off expectations, they also flower at a larger
      vegetative size, suggesting that warming probably causes acceleration in
      vegetative development. Although warming increases mean fitness (fruit
      production) by ca. 25%, there is a significant genotype-by-environment
      interaction. Changes in fitness rank indicate that imminent climate change can
      cause populations to be maladapted in their new environment, if adaptive
      evolution is limited. Thus, changes in the genetic composition of populations are
      likely, depending on the species' generation time and the speed of temperature
      change. Interestingly, genotypes that show stronger phenological responses have
      higher fitness under elevated temperatures, suggesting that phenological
      sensitivity might be a good indicator of success under elevated temperature at
      the genotypic level as well as at the species level. 

PMID- 24130096
TI  - Development of a steady-state FRET-based assay to identify inhibitors of the
      Keap1-Nrf2 protein-protein interaction.
AB  - One of the strategies proposed for the chemoprevention of degenerative diseases
      and cancer involves upregulation of antioxidant and free radical detoxification
      gene products by increasing the intracellular concentration of the transcription
      factor nuclear factor erythroid 2-related factor 2 (Nrf2). This can be achieved
      by disrupting the interaction between Nrf2 and Kelch-like ECH associated protein
      1 (Keap1), a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase
      complex. Here, we describe the development of a high-throughput fluorescence (or
      Forster) resonance energy transfer assay for the identification of inhibitors of
      the Keap1-Nrf2 protein-protein interaction (PPI). The basis of this assay is the
      binding of a YFP-conjugated Keap1 Kelch binding domain to a CFP-conjugated Nrf2
      derived 16-mer peptide containing a highly conserved "ETGE" motif. The
      competition aspect of the assay was validated using unlabeled Nrf2-derived 7-mer
      and 16-mer peptides and has potential as a screening tool for small molecule
      inhibitors of the PPI. We discuss the development of this assay in the context of
      other methods used to evaluate this PPI. 

PMID- 24130097
TI  - Randomized trial of print messaging: the role of the partner and monitoring style
      in promoting provider discussions about prostate cancer screening among African
      American men.
AB  - OBJECTIVE: Although African American (AA) men are at elevated risk for prostate
      cancer, medical guidelines do not present consistent screening recommendations
      for this group. However, all guidelines stress the need for screening decision
      making with a provider. This study evaluated the effectiveness of a brochure for
      the female partners of AA men, designed to help promote such discussion on the
      part of their mates. We also explored the effect of the partner's monitoring
      style (i.e., the extent to which the partner typically attends to health threats)
      on promoting discussion. METHODS: Female partners of AA men (N = 231) were
      randomized to receive either a prostate cancer screening Centers for Disease
      Control brochure for AA men, combined with a 'partner' brochure containing
      strategies to promote men's initiation of a provider visit to discuss screening,
      or the Centers for Disease Control brochure only and completed preintervention
      and post-intervention surveys online. RESULTS: The message groups did not differ
      on taking active steps to engage in provider discussion: relative risk ratio
      (RRR) = 0.99, p = .98; thinking about it: RRR = 1.13, p = .74. However, among
      partners who received the partner brochure, monitoring style was associated with
      'thinking about initiating a provider visit' on the part of the mate (RRR = 1.74,
      p < .01). Across conditions, monitoring style was also associated with 'taking
      active steps to initiate a provider visit' on the part of the mate (RRR = 1.38, p
      < .05). CONCLUSIONS: High monitoring partners may be effective in influencing
      their AA mates to initiate provider discussion, particularly when tailored
      messaging is provided.

PMID- 24130098
TI  - TB diagnostic process management of patients in a referral hospital in Mozambique
      in comparison with the 2007 WHO recommendations for the diagnosis of smear
      negative pulmonary TB and extrapulmonary TB.
AB  - BACKGROUND: In sub-Saharan African countries, the high proportion of smear
      negative pulmonary TB (SNTB) and extrapulmonary TB (EPTB) contributes to a delay
      in TB diagnosis and treatment. We evaluated the TB diagnostic process of adult
      patients with presumptive TB in a referral hospital in Mozambique according to
      the 2007 WHO recommendations for the diagnosis and treatment of SNTB and EPTB in
      HIV-prevalent resource-poor settings. METHODS: This was a retrospective, cross
      sectional study using medical records of patients admitted in June-July 2009.
      RESULTS: Overall, 514 patient records were screened, providing 234 presumptive TB
      patients. There were 70 deaths (29.9%). The evaluation of danger signs was never
      complete. HIV status was known for 175/234 patients (74.8%), 140 (80.0%) of whom
      were HIV-positive. A sputum smear microscopy (SSM) result was obtained for 59/234
      patients (25.2%). SSM results were positive in 8/59 patients (13.6%). Chest
      radiography was done in 150/234 patients (64.1%) and 103 (68.7%) were abnormal. A
      total of 66 patients (28.2%) received TB treatment. CONCLUSIONS: The TB
      diagnostic process in this Mozambican hospital remained largely incomplete
      according to WHO recommendations and few patients with presumptive TB were
      identified as TB patients. Deficiencies as described should prompt
      reconsideration of WHO guideline content and feasibility.

PMID- 24130099
TI  - Surgeon-performed ultrasound and transfacial sialoendoscopy for complete parotid
      duct stenosis.
AB  - A 57-year-old man presented with a 16-month history of right parotid swelling
      since undergoing a transoral sialolithotomy of the parotid duct. An ultrasound
      and a computed tomography scan showed a 6 cm-long dilated parotid duct without
      evidence of sialolithiasis or tumor mass. The complete Stensen's duct stenosis
      that was found was managed by a surgeon-performed ultrasound-guided transfacial
      needle catheterization of the dilated parotid duct, anterograde sialoendoscopy,
      recanalization of the duct, and stent placement. At 15 month follow-up, the
      patient reported no recurrent facial swelling or discomfort. Surgeon-performed
      ultrasound, combined with sialoendoscopy, can provide unique advantages for
      managing parotid duct stenosis and obstructive sialadenitis.

PMID- 24130100
TI  - Prometheus bound, but myriad loose ends: amid new legal battles over BRCA tests,
      technology may resolve what the courts have not.

PMID- 24130101
TI  - A difunctional squarylium indocyanine dye distinguishes dead cells through
      diverse staining of the cell nuclei/membranes.
AB  - Functionalized fluorescent dyes have attracted great interest for the specific
      staining of subcellular organelles in multicellular organisms. A novel nanometer
      sized water-soluble multi-functional squarylium indocyanine dye (D1) that
      contains four primary amines is synthesized. The dye exhibits good
      photostability, non-toxicity and biocompatibility. Isothermal titration
      calorimetry demonstrates that an affinity between D1 and DNA is higher than that
      between D1 and analogue of phospholipids. Analysis of circular dichroism spectra
      indicates that D1 targets to the DNA minor groove and aggregates to a helix.
      Because of the distinct affinity between the dye and subcellular organelles, the
      dye exhibits difunctional abilities to label the cell nuclei in fixed
      cells/tissue and the cell membranes in live cells/tissue. By combination of the
      two staining capabilities, the dye is further explored as a specific marker to
      distinguish apoptotic cells in live cells/tissue. The research opens a new way to
      design novel multifunctional dyes for life science applications. 

PMID- 24130102
TI  - About 1% of the breast and ovarian Spanish families testing negative for BRCA1
      and BRCA2 are carriers of RAD51D pathogenic variants.
AB  - RAD51D mutations have been recently identified in breast (BC) and ovarian cancer
      (OC) families. Although an etiological role in OC appears to be present, the
      association of RAD51D mutations and BC risk is more unclear. We aimed to
      determine the prevalence of germline RAD51D mutations in Spanish BC/OC families
      negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from
      BC/OC families, 171 BC families, 51 OC families and 129 patients without family
      history but with early-onset BC or OC or metachronous BC and OC. Mutation
      detection was performed with high-resolution melting, denaturing high-performance
      liquid chromatography or Sanger sequencing. Three mutations were found in four
      families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and
      c.667+2_667+23del, leading to the exon 7 skipping and one previously described:
      c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The
      c.667+2_667+23del cosegregated in the family with one early-onset BC and two
      bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which
      was predicted in silico to be potentially pathogenic. About 1% of the BC and OC
      Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The
      presence of several BC mutation carriers, albeit in the context of familial OC,
      suggests an increased risk for BC, which should be taken into account in the
      follow-up and early detection measures. RAD51D testing should be considered in
      clinical setting for families with BC and OC, irrespective of the number of OC
      cases in the family.

PMID- 24130103
TI  - Endovascular transluminal stent grafting: Treatment of choice for post lumbar
      spine surgery iliac arterio-venous fistulae.
AB  - Iliac vessels are prone to injury during lumbar spine surgery due to their
      proximity to the lumbar spine. Arterio-venous fistula formation during lumbar
      spine surgery is an uncommon complication and can present as an asymptomatic
      incidental finding to rapidly deteriorating hemodynamics leading to
      cardiopulmonary collapse. We have reported three patients who had symptomatic
      iliac arterio-venous fistula detected soon after lumbar spine surgery. All these
      patients were successfully treated by endovascular transluminal stent grafting.
      (c) 2013 Wiley Periodicals, Inc.

PMID- 24130104
TI  - Supercritical carbon dioxide: a promoter of carbon-halogen bond heterolysis.

PMID- 24130105
TI  - Arterial spin labeling with simultaneous multi-slice echo planar imaging.
AB  - PURPOSE: Simultaneous multi-slice (SMS) echo planar imaging (EPI) is incorporated
      into two-dimensional (2D) arterial spin labeling (ASL) imaging to produce more
      slices for measuring perfusion in a larger region of the brain than currently
      possible with multi-slice EPI. METHODS: Pulsed ASL (PASL) preparations using FAIR
      and QUIPSS II techniques were combined with SMS-EPI. Testing was performed in
      four subjects at 3 Tesla. Multiband slice acceleration factors (MB) from MB-2 to
      MB-5 using 40 averages were evaluated. Comparisons were made quantitatively to
      PASL 2D EPI and qualitatively to PASL 3D GRASE. RESULTS: In the 12 slice data
      set, spatial SNR for the perfusion weighted images averaged across subjects was
      3.28 and 3.44 for the two sequential MB-1 acquisitions as control comparison,
      3.25 for MB-2 and 2.98 for MB-3. The temporal SNR averaged 1.01 and 0.99 for MB
      1, 0.89 for MB-2, and 0.78 for MB-3. For whole-brain spatial coverage, the 20
      slice data sets could be acquired in narrower time windows, from 874 ms using EPI
      (MB-1) down to 196 ms using MB-5. SMS-EPI ASL differed from 3D GRASE ASL, which
      can use background suppression and has less susceptibility artifact as a CPMG SE
      sequence. CONCLUSION: SMS-EPI has a major advantage over EPI-based ASL imaging by
      increasing slice coverage without lengthening the acquisition time window.

PMID- 24130109
TI  - Corniculate reconstruction after arytenoid resection in supracricoid
      laryngectomy.

PMID- 24130110
TI  - Pou5f1 protein expression and posttranslational modification during early
      zebrafish development.
AB  - BACKGROUND: Pou5f1/Oct4 is a transcription factor essential for maintenance of
      pluripotency in mammals and for control of blastula and gastrula stage gene
      regulatory networks in zebrafish. Information on Pou5f1 protein distribution was
      before this study not available for zebrafish. Therefore, we generated polyclonal
      antibodies that selectively recognize Pou5f1 and analyzed its protein
      distribution and modification during development. RESULTS: Pou5f1 protein is
      present in unfertilized oocytes, and persists in all embryonic and enveloping
      layer cell nuclei until the end of gastrulation, but is absent from yolk
      syncytial nuclei. Pou5f1 is subject to multiple developmentally regulated
      phosphorylations, with the higher phosphorylated forms prevailing in the oocyte
      and during late gastrulation. CONCLUSIONS: The developmental protein profile
      correlates with the stages during which deep cells are not committed to a
      specific germ layer. The posttranslational modification by phosphorylation opens
      the possibility that Pou5f1 may be subject to temporal or region specific
      modulation of its activity or stability by embryonic signaling mechanisms.

PMID- 24130112
TI  - Optical metabolic imaging identifies glycolytic levels, subtypes, and early
      treatment response in breast cancer.
AB  - Abnormal cellular metabolism is a hallmark of cancer, yet there is an absence of
      quantitative methods to dynamically image this powerful cellular function.
      Optical metabolic imaging (OMI) is a noninvasive, high-resolution, quantitative
      tool for monitoring cellular metabolism. OMI probes the fluorescence intensities
      and lifetimes of the autofluorescent metabolic coenzymes reduced NADH and flavin
      adenine dinucleotide. We confirm that OMI correlates with cellular glycolytic
      levels across a panel of human breast cell lines using standard assays of
      cellular rates of glucose uptake and lactate secretion (P < 0.05, r = 0.89). In
      addition, OMI resolves differences in the basal metabolic activity of
      untransformed from malignant breast cells (P < 0.05) and between breast cancer
      subtypes (P < 0.05), defined by estrogen receptor and/or HER2 expression or
      absence. In vivo OMI is sensitive to metabolic changes induced by inhibition of
      HER2 with the antibody trastuzumab (herceptin) in HER2-overexpressing human
      breast cancer xenografts in mice. This response was confirmed with tumor growth
      curves and stains for Ki67 and cleaved caspase-3. OMI resolved trastuzumab
      induced changes in cellular metabolism in vivo as early as 48 hours posttreatment
      (P < 0.05), whereas fluorodeoxyglucose-positron emission tomography did not
      resolve any changes with trastuzumab up to 12 days posttreatment (P > 0.05). In
      addition, OMI resolved cellular subpopulations of differing response in vivo that
      are critical for investigating drug resistance mechanisms. Importantly, OMI
      endpoints remained unchanged with trastuzumab treatment in trastuzumab-resistant
      xenografts (P > 0.05). OMI has significant implications for rapid cellular-level
      assessment of metabolic response to molecular expression and drug action, which
      would greatly accelerate drug development studies.

PMID- 24130113
TI  - The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity.
AB  - GNF-2, a tyrosine kinase inhibitor, was developed to overcome imatinib-resistant
      mutations found in CML patients. Osteoclasts are the principal bone-resorbing
      cells that are responsible for bone diseases, such as osteoporosis, tumor-induced
      osteolysis, and metastatic cancers. In this study, we investigated the effect of
      GNF-2 on osteoclast development induced by RANKL and M-CSF. We found that GNF-2
      inhibited osteoclast differentiation from BMMs. GNF-2 suppressed RANKL-induced NF
      kappaB transcriptional activity and the induction of c-Fos and NFATc1, which are
      two key transcription factors in osteoclastogenesis. We also observed that GNF-2
      dose-dependently inhibited the proliferation of osteoclast precursors through the
      suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast
      apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered
      with actin cytoskeletal organization and subsequently blocked the bone-resorbing
      activity of mature osteoclasts. In agreement with its in vitro effects, GNF-2
      reduced osteoclast number and bone loss in a mouse model of LPS-induced bone
      destruction. Taken together, our data reveal that GNF-2 possesses anti-bone
      resorptive properties, suggesting that GNF-2 may have therapeutic value for the
      treatment of bone-destructive disorders that can occur as a result of excessive
      osteoclastic bone resorption. 

PMID- 24130116
TI  - Geometry-mediated enhancement of single-ion anisotropy: a route to single
      molecule magnets with a high blocking temperature.
AB  - Not just any old iron ion: A linear, two-coordinate ionic Fe(I) complex with a
      S=3/2 ground state has a large energy barrier for magnetization reversal, Ueff
      =226 cm(-1) , and undergoes slow magnetic relaxation in the absence of an applied
      magnetic field. The preparation of complexes with these properties is a step
      towards the eventual practical application of single-molecule magnets. 

PMID- 24130115
TI  - Percutaneous cardiac assist devices compared with surgical hemodynamic support
      alternatives: cost-effectiveness in the emergent setting.
AB  - This study evaluates the cost-effectiveness of percutaneous cardiac assist device
      (pVAD) therapy in the emergent setting compared with traditional surgical
      hemodynamic support alternatives. BACKGROUND: Previous research has demonstrated
      the cost-effectiveness of pVAD hemodynamic support for patients undergoing high
      risk percutaneous coronary intervention. For patients in cardiogenic shock (CS),
      use of pVAD therapy has been shown to reduce length of stay (LOS). METHODS:
      National utilization and outcome data from the 2010-2011 MedPAR and state
      sponsored all-payer databases were collected for patients with an acute
      myocardial infarction complicated by CS who were treated with either a pVAD (n =
      883) or with traditional surgical hemodynamic support alternatives (ECMO and
      extracorporeal VAD) (n = 305). RESULTS: Discharge survival was greater with pVADs
      than with surgical alternatives (56% vs. 42%, P < 0.001) and was achieved with a
      strong trend toward reduced LOS (13.2 and 17.9 days, respectively, P = 0.055) and
      a significantly lower cost of the index admission ($90,929 and $144,257,
      respectively, P < 0.001). Cost-effectiveness analysis based on the national data
      demonstrated that pVAD achieved improved outcomes at lower cost. Data were also
      collected for similar patients who underwent protocol-guided pVAD therapy (using
      Impella 2.5) at PinnacleHealth, between 2009 and 2011 (n = 30). At this site, the
      survival rate increased to 60%, length of hospitalization was shortened to 6
      days, and admission costs were lowered to $53,850 relative to the surgical
      alternatives strategy. CONCLUSIONS: For patients in CS requiring emergent
      hemodynamic support, pVAD therapy offers a less invasive alternative that can be
      deployed sooner, resulting in better outcomes, shorter LOS, lower costs and with
      no incremental cost, and a survival benefit when compared with traditional
      surgical hemodynamic support alternatives. PVAD therapy (and Impella 2.5 in
      particular) is emerging as a dominant strategy for this challenging patient
      population.

PMID- 24130117
TI  - Effects of letter-identification training on letter naming in prereading
      children.
AB  - Three prereading children who named 0 to 3 of 20 targeted letters were taught to
      select the 20 printed letters when they heard spoken letter names. For all
      participants, letter-identification training resulted in naming for the majority
      of letters. 

PMID- 24130118
TI  - A test of three hypotheses of pica and amylophagy among pregnant women in Tamil
      Nadu, India.
AB  - OBJECTIVES: Pica has been studied in India and elsewhere for more than 100 years,
      yet no compelling and empirically well-supported explanation for it has emerged.
      Amylophagy, sometimes considered a type of pica and sometimes studied separately,
      is less frequently investigated and also lacks a convincing explanation. This
      study used a biocultural approach to test three hypotheses of pica and
      amylophagy: protection, hunger/nutrition, and psychological distress. METHODS:
      The research took place in Tamil Nadu, India. In study 1, a cultural
      investigation was carried out among nonpregnant, adult women (n = 54) to
      determine nonfood substances that are consumed in this region and perceptions of
      health consequences. Next, using the substances identified in Study 1, three
      hypotheses of pica and amylophagy were tested in a cross-sectional study of
      pregnant women (Study 2, n = 95). Logistic regression analysis was used to
      analyze the presence or absence of engaging in pica and amylophagy. A series of
      bivariate analyses were used to examine the variation in amount and frequency of
      consumption. RESULTS: Study 1 revealed that cultural attitudes strongly shape the
      selection of nonfood substances. In Study 2, the presence or absence of pica was
      not predicted by any of the variables included in the study, whereas the
      frequency and amount of consumption of pica substances were primarily explained
      by the psychological distress and hunger/nutrition hypotheses. Both the presence
      or absence of amylophagy as well as the frequency and amount of consumption were
      best explained by the protection hypothesis. CONCLUSIONS: This research provided
      partial support for the protection and hunger/nutrition hypotheses for
      amylophagy, and also provided some evidence for the role of psychological
      distress and hunger or nutrition in pica.

PMID- 24130120
TI  - Right heart catheterization using antecubital venous access: feasibility, safety
      and adoption rate in a tertiary center.
AB  - OBJECTIVES: To determine feasibility, safety, and adoption rates of right heart
      catheterization (RHC) using antecubital venous access (AVA) as compared to using
      the traditional approach of proximal venous access (PVA). BACKGROUND: RHC via PVA
      (i.e., internal jugular, femoral or subclavian) is generally a low risk
      procedure; however, complications may occur and are usually access site related.
      RHC via an antecubital approach has regained attention given the increase in
      transradial left heart catheterizations. METHODS: Patients undergoing RHC for any
      indication at a single large academic medical center were identified over a 5
      year period (January 2008 to December 2012) from a database. Medical records were
      retrospectively analyzed for demographic, procedural and outcomes data. RESULTS:
      Two hundred seventy-two RHC procedures were included (106 AVA, 166 PVA). The
      adoption rate of AVA for RHC increased rapidly since its introduction in our
      laboratory in 2010 (100% PVA in 2008 and 2009, 85% AVA in 2012). All procedures
      were successful; however, 6% of procedures required additional, alternate access
      to the original site. Initial success rates were similar in the two groups (91
      vs. 96% for AVA and PVA respectively, P = 0.12). Fluoroscopy time was shorter in
      the group of patients who underwent the procedure via AVA. The complication rate
      was 0% in the AVA group compared with 3% in the PVA group (P = 0.16). CONCLUSION:
      RHC via the AVA is a feasible and safe alternative to PVA. Our experience and
      rapid adoption support the use AVA as the access site of choice for RHC in
      uncomplicated patients.

PMID- 24130119
TI  - Functional linear models for association analysis of quantitative traits.
AB  - Functional linear models are developed in this paper for testing associations
      between quantitative traits and genetic variants, which can be rare variants or
      common variants or the combination of the two. By treating multiple genetic
      variants of an individual in a human population as a realization of a stochastic
      process, the genome of an individual in a chromosome region is a continuum of
      sequence data rather than discrete observations. The genome of an individual is
      viewed as a stochastic function that contains both linkage and linkage
      disequilibrium (LD) information of the genetic markers. By using techniques of
      functional data analysis, both fixed and mixed effect functional linear models
      are built to test the association between quantitative traits and genetic
      variants adjusting for covariates. After extensive simulation analysis, it is
      shown that the F-distributed tests of the proposed fixed effect functional linear
      models have higher power than that of sequence kernel association test (SKAT) and
      its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the
      causal variants are all rare, (2) the causal variants are both rare and common,
      and (3) the causal variants are common. The superior performance of the fixed
      effect functional linear models is most likely due to its optimal utilization of
      both genetic linkage and LD information of multiple genetic variants in a genome
      and similarity among different individuals, while SKAT and SKAT-O only model the
      similarities and pairwise LD but do not model linkage and higher order LD
      information sufficiently. In addition, the proposed fixed effect models generate
      accurate type I error rates in simulation studies. We also show that the
      functional kernel score tests of the proposed mixed effect functional linear
      models are preferable in candidate gene analysis and small sample problems. The
      methods are applied to analyze three biochemical traits in data from the Trinity
      Students Study. 

PMID- 24130122
TI  - Seasonal and socioeconomic influences on thyroid function among the Yakut (Sakha)
      of Eastern Siberia.
AB  - OBJECTIVES: Previous research has shown that the extreme cold and short day
      lengths of polar winters promote increased production and uptake of thyroid
      hormones, resulting in marked declines in free triiodothyronine (fT3). However,
      this "polar T3 syndrome" has been documented almost exclusively on small samples
      of male sojourners and little is known about seasonal changes in thyroid function
      among indigenous circumpolar groups. The present study addresses this gap by
      examining seasonal changes in thyroid hormone levels among the indigenous Yakut
      (Sakha) of northeastern Siberia. METHODS: Anthropometric dimensions and thyroid
      measures (fT3, free thyroxine [fT4], thyroid-stimulating hormone [TSH]) were
      obtained on two occasions (July/August, 2009 and January 2011) on a sample of 134
      Yakut adults (51 men, 83 women) from the village of Berdygestiakh, Sakha
      Republic/Yakutia, Russia. RESULTS: Yakut men and women both displayed significant
      declines in fT3 and fT4, and significant increases in TSH from summer to winter
      despite showing only modest seasonal changes in body mass and composition. Among
      men, gains in fat-free mass (FFM) were associated with larger reductions in fT3
      and greater increases in TSH. Men living more traditional lifeways showed larger
      winter declines in fT4 and greater increases in TSH. CONCLUSIONS: The Yakut
      exhibited significant winter declines in fT3 levels similar to other circumpolar
      groups studied. However, the magnitude of seasonal change was greater in the
      Yakut, perhaps reflecting their distinctive metabolic physiology. Lifestyle
      factors play a mediating role in thyroid responses, such that men with more
      traditional lifeways had more exaggerated seasonal changes.

PMID- 24130121
TI  - Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-variant
      patients reveals 12 new disease-causing POLH mutations.
AB  - Xeroderma pigmentosum variant (XP-V) is a rare genetic disease, characterized by
      some sunlight sensitivity and predisposition to cutaneous malignancies. We
      described clinical and genetic features of the largest collection ever published
      of 23 XPV patients (ages between 21 and 86) from 20 unrelated families. Primary
      fibroblasts from patients showed normal nucleotide excision repair but UV
      hypersensitivity in the presence of caffeine, a signature of the XP-V syndrome.
      87% of patients developed skin tumors with a median age of 21 for the first
      occurrence. The median numbers of basal-cell carcinoma was 13 per patient, six
      for squamous-cell carcinoma, and five for melanoma. XP-V is due to defects in the
      translesion-synthesis DNA polymerase Poleta coded by the POLH gene. DNA
      sequencing of POLH revealed 29 mutations, where 12 have not been previously
      identified, leading to truncated polymerases in 69% of patients. Four missense
      mutations are correlated with the protein stability by structural modeling of the
      Poleta polymerase domain. There is a clear relationship between the types of
      missense mutations and clinical severity. For truncating mutations, which lead to
      an absence of or to inactive proteins, the life-cumulated UV exposure is probably
      the best predictor of cancer incidence, reinforcing the necessity to protect XP
      Vs from sun exposure.

PMID- 24130123
TI  - Treatment of congenital non-ductal shunt lesions with the amplatzer duct occluder
      II.
AB  - : Amplatzer Duct Occluder II (ADO II) is especially designed for closing long
      ducts in infants. The experience with off-label use of ADO II in non-ductal
      positions is limited. AIM: To evaluate feasibility of use of ADO II in non-ductal
      positions, incidence of complete heart block (CHB), advantages and disadvantages.
      MATERIAL AND RESULTS: Out of 79 defects closed with ADO II, 61 had
      perimembranous, 12 apical/mid-muscular ventricular septal defects (VSD), 4
      Gerbode defects, one each of coronary arterio-venous fistula and aorto-right
      ventricular tunnel. Age ranged from 8 months to 21 years (mean 8.9 +/- 4.02
      years, median 9 years). The mean fluoroscopy time was 5.2 +/- 1.1 min with range
      4.2-9.2 min. Complete closure was achieved in all. Three cases developed
      transient junctional bradycardia, treated with steroids. One patient who
      developed CHB (1.3%) needed temporary pacing. DISCUSSION: ADO II is a low profile
      device. It can be easily delivered through a 5F guiding catheter and needs very
      short fluoroscopic time as arteriovenous loop is not needed. The cost is 1/3 of
      regular ventricular septal occluders. The CHB that is a major challenge for
      closure of VSDs is less common with soft, specially designed ADO II, which does
      not compress the conducting system. CONCLUSIONS: Use of the ADO II in non-ductal
      positions can be achieved with high success and low complication rates,
      especially CHB; its use is also associated with significantly reduced procedure
      time and device cost. Device size availability restricts use of the ADO II to
      defects up to 6 mm in diameter. (c) 2013 Wiley Periodicals, Inc.

PMID- 24130124
TI  - Subtle gait changes in patients with REM sleep behavior disorder.
AB  - Many people with rapid eye movement (REM) sleep behavior disorder (RBD) have an
      underlying synucleinopathy, the most common of which is Lewy body disease.
      Identifying additional abnormal clinical features may help in identifying those
      at greater risk of evolving to a more severe syndrome. Because gait disorders are
      common in the synucleinopathies, early abnormalities in gait in those with RBD
      could help in identifying those at increased risk of developing overt
      parkinsonism and/or cognitive impairment. We identified 42 probable RBD subjects
      and 492 controls using the Mayo Sleep Questionnaire and assessed gait velocity,
      cadence, and stride dynamics with an automated gait analysis system. Cases and
      controls were similar in age (79.9 +/- 4.7 and 80.1 +/- 4.7, P = 0.74), Unified
      Parkinson's Disease Rating Scale Part III (UPDRS) score (3.3 +/- 5.5 and 1.9 +/-
      4.1, P = 0.21) and Mini-Mental State Examination scores (27.2 +/- 1.9 and 27.7 +/
      1.6, P = 0.10). A diagnosis of probable RBD was associated with decreased
      velocity (-7.9 cm/s; 95% confidence interval [CI], -13.8 to -2.0; P < 0.01),
      cadence (-4.4 steps/min; 95% CI, -7.6 to -1.3; P < 0.01), significantly increased
      double limb support variability (30%; 95% CI, 6-60; P = 0.01), and greater stride
      time variability (29%; 95% CI, 2-63; P = 0.03) and swing time variability (46%;
      95% CI, 15-84; P < 0.01). Probable RBD is associated with subtle gait changes
      prior to overt clinical parkinsonism. Diagnosis of probable RBD supplemented by
      gait analysis may help as a screening tool for disorders of alpha-synuclein.

PMID- 24130126
TI  - Transcatheter aortic valve replacement: a novel abdominal transaortic approach.
AB  - Transcatheter aortic valve replacement (TAVR) via the transfemoral (TF),
      transapical (TA), or even the transaortic (TAO) approach in high-risk or
      inoperable patients is quickly becoming a safe and effective modality for the
      treatment of symptomatic severe aortic stenosis (AS). However, in this selected
      group of patients, those with anatomical or physiologic constraints preventing
      TF, TA, and conventional TAO TAVR, alternative sites of access must be explored.
      Here, we report a successful TAVR in an inoperable patient with severe AS using a
      distal abdominal TAO approach via a synthetic graft-conduit.

PMID- 24130125
TI  - High frequency strand slippage mutations in CTCF in MSI-positive endometrial
      cancers.
AB  - Tumors with defective mismatch repair acquire large numbers of strand slippage
      mutations including frameshifts in coding sequence repeats. We identified a
      mutational hotspot, p.T204fs, in the insulator-binding protein (CTCF) in MSI
      positive endometrial cancers. Although CTCF was described as a significantly
      mutated gene by the endometrial cancer TCGA, the A7 track variants leading to
      T204 frameshifts were not reported. Reanalysis of TCGA data using Pindel revealed
      frequent T204fs mutations, confirming CTCF is an MSI target gene and revealed the
      same frameshifts in tumors with intact mismatch repair. We show that T204fs
      transcripts are subject to nonsense-mediated decay and as such, T204fs mutations
      are unlikely to act as dominant negatives. The spectrum and pattern of mutations
      observed is consistent with CTCF acting as a haploinsufficient tumor suppressor.

PMID- 24130127
TI  - Reply: To PMID 23737007.

PMID- 24130128
TI  - Development and validation of assay protocols for use with dried blood spot
      samples.
AB  - Dried blood spots (DBS)--drops of capillary whole blood collected from finger
      stick--represent a minimally invasive alternative to venipuncture that
      facilitates the collection of blood samples from research participants in
      naturalistic, field-based research settings. But the number of validated assays
      for quantifying biomarkers in DBS samples is relatively low in comparison with
      serum or plasma. The objective of this review is to discuss the advantages and
      disadvantages of DBS sampling, and to outline the steps involved in developing
      and validating an immunoassay for application to DBS samples. These steps include
      deciding on reagents, preparing calibration and quality control material,
      evaluating elution protocols, optimizing sample quantity, and assessing multiple
      aspects of assay performance, including intra- and interassay variation, lower
      limit of detection, accuracy, stability, and agreement between results from
      matched DBS and plasma samples. The broader goal of this "how-to" approach is to
      encourage investigators to validate, implement, and disseminate assay protocols
      for DBS samples in order to advance field-based research on human biology.

PMID- 24130130
TI  - Prolactin actions.
AB  - Molecular genetics and other contemporary approaches have contributed to a better
      understanding of prolactin (PRL) actions at the cellular and organismal levels.
      In this review, several advances in knowledge of PRL actions are highlighted.
      Special emphasis is paid to areas of progress with consequences for understanding
      of human PRL actions. The impacts of these advances on future research priorities
      are analyzed. 

PMID- 24130129
TI  - Towards an understanding of cell-specific functions of signal-dependent
      transcription factors.
AB  - The ability to regulate gene expression in a cell-specific manner is a feature of
      many broadly expressed signal-dependent transcription factors (SDTFs), including
      nuclear hormone receptors and transcription factors that are activated by cell
      surface receptors for extracellular signals. As the most plastic cells of the
      hematopoietic system, macrophages are responsive to a wide spectrum of regulatory
      molecules and provide a robust model system for investigation of the basis for
      cell-specific transcriptional responses at a genome-wide level. Here, focusing on
      recent studies in macrophages, we review the evidence suggesting a model in which
      cell-specific actions of SDTFs are the consequence of priming functions of
      lineage determining transcription factors. We also discuss recent findings
      relating lineage-determining and SDTF activity to alterations in the epigenetic
      landscape as well as the production and function of enhancer RNAs. These findings
      have implications for the understanding of how natural genetic variation impacts
      cell-specific programs of gene expression and suggest new approaches for altering
      gene expression in vivo. 

PMID- 24130132
TI  - Dual catalysis becomes diastereodivergent.

PMID- 24130131
TI  - Two actin-interacting protein 1 isoforms function redundantly in the somatic
      gonad and are essential for reproduction in Caenorhabditis elegans.
AB  - The somatic gonad of the nematode Caenorhabditis elegans exhibits highly
      regulated contractility during ovulation, which is essential for successful
      reproduction. Nonstriated actin filament networks in the myoepithelial sheath at
      the proximal ovary provide contractile forces to push a mature oocyte for
      ovulation, but the mechanism of assembly and regulation of the contractile actin
      networks is poorly understood. Here, we show that actin-interacting protein 1
      (AIP1) is essential for the assembly of the contractile actin networks in the
      myoepithelial sheath. AIP1 promotes disassembly of actin filaments in the
      presence of actin depolymerizing factor (ADF)/cofilin. C. elegans has two AIP1
      genes, unc-78 and aipl-1. Mutation or RNA interference of a single AIP1 isoform
      causes only minor impacts on reproduction. However, simultaneous depletion of the
      two AIP1 isoforms causes sterility. AIP1-depleted animals show very weak
      contractility of the myoepithelial sheath and fail to ovulate a mature oocyte,
      which results in accumulation of endomitotic oocytes in the ovary. Depletion of
      AIP1 prevents assembly of actin networks and causes abnormal aggregation of actin
      as well as ADF/cofilin in the myoepithelial sheath. These results indicate that
      two AIP1 isoforms have redundant roles in assembly of the contractile apparatuses
      necessary for C. elegans reproduction.

PMID- 24130133
TI  - The mismatch repair protein MSH2 is rate limiting for repeat expansion in a
      fragile X premutation mouse model.
AB  - Fragile X-associated tremor and ataxia syndrome, Fragile X-associated primary
      ovarian insufficiency, and Fragile X syndrome are Repeat Expansion Diseases
      caused by expansion of a CGG*CCG-repeat microsatellite in the 5 UTR of the FMR1
      gene. To help understand the expansion mechanism responsible for these disorders,
      we have crossed mice containing~147 CGG*CCG repeats in the endogenous murine Fmr1
      gene with mice containing a null mutation in the gene encoding the mismatch
      repair protein MSH2. MSH2 mutations are associated with elevated levels of
      generalized microsatellite instability. However, we show here for the first time
      that in the FX mouse model, all maternally and paternally transmitted expansions
      require Msh2. Even the loss of one Msh2 allele reduced the intergenerational
      expansion frequency significantly. Msh2 is also required for all somatic
      expansions and loss of even one functional Msh2 allele reduced the extent of
      somatic expansion in some organs. Tissues with lower levels of MSH2 were more
      sensitive to the loss of a single Msh2 allele. This suggests that MSH2 is rate
      limiting for expansion in this mouse model and that MSH2 levels may be a key
      factor that accounts for tissue-specific differences in expansion risk.

PMID- 24130134
TI  - Letter by Kurtoglu et al regarding article, "Asymmetric dimethylarginine in
      response to recombinant tissue-type plasminogen activator and erythropoietin in
      acute stroke".

PMID- 24130135
TI  - Response to letter regarding article, "Asymmetric dimethylarginine in response to
      recombinant tissue-type plasminogen activator and erythropoietin in acute
      stroke".

PMID- 24130136
TI  - Young patient with aphasia, monoparesis, facial drop, facial sensory loss,
      diplopia, dysarthria, and vertical gaze palsy.

PMID- 24130137
TI  - Improved detection of silent atrial fibrillation using 72-hour Holter ECG in
      patients with ischemic stroke: a prospective multicenter cohort study.
AB  - BACKGROUND AND PURPOSE: Adequate diagnosis of atrial fibrillation (AF), including
      paroxysmal AF, is an important part of stroke workup. Prolonged ECG monitoring
      may improve the detection of paroxysmal, previously undiagnosed AF (unknown AF).
      Therefore, we evaluated systematic 72-hour Holter ECG monitoring to detect
      unknown AF for the workup of patients with stroke. METHODS: Unselected survivors
      of a stroke or transient ischemic attack (TIA) without known AF were enrolled in
      a prospective, multicenter cohort study of 72-hour Holter ECG monitoring in 9
      German secondary and tertiary stroke centers between May 2010 and January 2011.
      In addition to standardized workup of stroke pathogenesis according to the German
      Stroke Unit protocol, all patients underwent 72-hour Holter ECG monitoring
      directly after admission. All ECGs were centrally analyzed by 2 independent
      observers. We determined the proportion of unknown AF and compared the detection
      rates of 72- and 24-hour monitoring. RESULTS: A total of 1135 patients were
      enrolled (mean age, 67 years [SD, 13.1 years], 45% women, 29% TIA). Unknown AF
      was detected in 49 out of 1135 patients (4.3%, [95% confidence interval, 3.4
      5.2%]) by 72-hour ECG monitoring. Unknown AF was diagnosed in 29 patients (2.6%)
      within the first 24 hours of ECG monitoring, and in 20 more patients only by 72
      hours of ECG monitoring. The number needed to screen by 72-hour ECG was 55
      patients (95% confidence interval [35-123]) for each additional AF diagnosis.
      Patients with unknown AF were significantly older and had more often a history of
      previous stroke. Patients with unknown AF were equally distributed within
      categories of pathogenesis according to Trial of Org 10172 in Acute Stroke
      Treatment (TOAST) classification. CONCLUSIONS: In unselected survivors of stroke
      or TIA, 72-hour ECG monitoring is feasible and improves the detection rate of
      silent paroxysmal AF.

PMID- 24130138
TI  - Sex is associated with the presence of atherosclerotic plaque hemorrhage and
      modifies the relation between plaque hemorrhage and cardiovascular outcome.
AB  - BACKGROUND AND PURPOSE: Plaque hemorrhage (PH) may lead to accelerated
      progression of atherosclerotic disease. The presence of local PH in the carotid
      plaque predicts future cardiovascular events in any vascular territory. We
      investigated the prevalence of local PH and the predictive value of PH for the
      occurrence of cardiovascular events in men and women separately. METHODS:
      Atherosclerotic plaques from 1422 patients (969 men, 453 women) who underwent
      carotid endarterectomy were analyzed histologically for the presence of PH.
      Patients were monitored for 3 years for cardiovascular events (nonfatal stroke,
      nonfatal myocardial infarction, vascular death, and vascular intervention).
      RESULTS: Plaques from men showed a significantly higher prevalence of PH compared
      with women (67% versus 54%; P<0.001). In 1353 patients with available follow-up
      data, with a median duration of 2.9 years, 270 events had occurred in men (29%)
      and 94 in women (22%). Stratified by presence of PH, the event rate was 32% in
      men with PH versus 23% in men without PH, and 23% in women with PH versus 21% in
      women without PH. A multivariable Cox proportional hazards model found a
      significant interaction between sex and PH. PH was significantly associated with
      events in men (adjusted hazard ratio, 1.9; 95% CI, 1.2-2.8) but not in women
      (adjusted hazard ratio, 1.0; 95% CI, 0.6-1.7). CONCLUSIONS: Atherosclerotic
      carotid plaques obtained from men reveal a higher prevalence of PH compared with
      women. Local PH is strongly related to secondary manifestations of cardiovascular
      disease in men but not in women.

PMID- 24130140
TI  - Vasculogenesis in experimental stroke after human cerebral endothelial cell
      transplantation.
AB  - BACKGROUND AND PURPOSE: Despite the reported functional recovery in transplanted
      stroke models and patients, the mechanism of action underlying stem cell therapy
      remains not well understood. Here, we examined the role of stem cell-mediated
      vascular repair in stroke. METHODS: Adult rats were exposed to transient
      occlusion of the middle cerebral artery and 3 hours later randomly
      stereotaxically transplantated with 100K, 200K, or 400K human cerebral
      endothelial cell 6 viable cells or vehicle. Animals underwent neurological
      examination and motor test up to day 7 after transplantation then euthanized for
      immunostaining against neuronal, vascular, and specific human antigens. A
      parallel in vitro study cocultured rat primary neuronal cells with human cerebral
      endothelial cell 6 under oxygen-glucose deprivation and treated with vascular
      endothelial growth factor (VEGF) and anti-VEGF. RESULTS: Stroke animals that
      received vehicle infusion displayed typical occlusion of the middle cerebral
      artery-induced behavioral impairments that were dose-dependently reduced in
      transplanted stroke animals at days 3 and 7 after transplantation and accompanied
      by increased expression of host neuronal and vascular markers adjacent to the
      transplanted cells. Some transplanted cells showed a microvascular phenotype and
      juxtaposed to the host vasculature. Infarct volume in transplanted stroke animals
      was significantly smaller than vehicle-infused stroke animals. Moreover, rat
      neurons cocultured with human cerebral endothelial cell 6 or treated with VEGF
      exhibited significantly less oxygen-glucose deprivation-induced cell death that
      was blocked by anti-VEGF treatment. CONCLUSIONS: We found attenuation of
      behavioral and histological deficits coupled with robust vasculogenesis and
      neurogenesis in endothelial cell-transplanted stroke animals, suggesting that
      targeting vascular repair sets in motion a regenerative process in experimental
      stroke possibly via the VEGF pathway.

PMID- 24130141
TI  - Review of cerebral aneurysm formation, growth, and rupture.

PMID- 24130142
TI  - Waterpipe tobacco dependence in U.K. male adult residents: a cross-sectional
      study.
AB  - INTRODUCTION: The prevalence of waterpipe tobacco smoking (WPTS) is increasing
      worldwide. The aims of this study were (a) to evaluate the psychometric
      properties of the Lebanon Waterpipe Dependence Scale (LWDS-11), and (b) to
      assess, estimate, and identify factors associated with waterpipe tobacco
      dependence symptoms among U.K. male adult resident waterpipe tobacco smokers.
      METHODS: A total of 180 waterpipe tobacco smokers were recruited during random
      visits to 7 outlets serving waterpipe tobacco. Data were collected via face-to
      face interviews using the WPTS module of the Global Adult Tobacco Survey and the
      LWDS-11. Descriptive statistics, exploratory psychometric, univariate, and
      Poisson regression analysis were employed. RESULTS: Participants' M/SD age was
      29.46/+/-9.41 years, Arabic ethnicity accounted for 58.3%, and 53.9% had
      completed more than secondary education. Psychometric analyses for the LWDS-10,
      after removing 1 item from the generic scale, revealed Cronbach's alpha
      coefficient = 0.74. About 47% of the sample demonstrated waterpipe tobacco
      dependence. Being Arab (p = .040, OR = 2.63, 95% CI = 1.05-6.62), smoking
      waterpipe daily in the past (p = .003, OR = 2.13, 95% CI = 1.30-3.49), and an
      increase in length in the last session of WPTS (p = .044, OR = 1.15, 95% CI =
      1.00-1.32) were identified as risk factors for waterpipe tobacco dependence.
      CONCLUSIONS: This study demonstrated the potential of LWDS-11 and revealed 2
      domains: positive and negative reinforcement and physiological dependence.
      Results indicated that waterpipe tobacco smokers in the United Kingdom
      demonstrated tobacco dependence symptoms, which were associated with socio
      behavioral factors. Generalizability of these findings and their implications in
      public health are yet to be investigated.

PMID- 24130143
TI  - Household smoking restrictions related to secondhand smoke exposure in Guangdong,
      China: a population representative survey.
AB  - INTRODUCTION: China has a higher household secondhand smoke exposure rate than
      other countries. This study aims to estimate the prevalence rate of households
      implementing smoking bans in Guangdong and to identify factors correlated with
      household smoking bans. METHODS: A cross-sectional, stratified random cluster
      sampling survey was conducted in Guangdong in 2010. A total of 2,114 adults aged
      15 and older completed the face-to-face interviews with a response rate of 70%.
      The survey employed an adapted and validated questionnaire from the China Global
      Adult Tobacco Survey. Household smoking policy was divided into 3 groups: full
      ban, partial ban, and no ban. A multiple logistic regression model was employed
      to explore factors related to a full household smoking ban. RESULTS: The survey
      found 14.2% of respondents reported a full ban, 23.6% reported a partial ban, and
      62.2% reported no ban of smoking at home. Current smoking status was the
      strongest predictor for less restrictive household smoking policies (odds ratio
      [OR] = 4.9, 95% CI = 2.634-8.999). Our study suggested that people with a high
      level of education were more likely to implement a full household smoking ban (OR
      = 4.4, 95% CI = 2.388-8.178). Additionally, urban residents were significantly
      more likely to report a full household smoking ban than rural residents (OR =
      1.67, 95% CI = 1.202-2.322). CONCLUSIONS: Household smoking bans were not
      sufficiently established in Guangdong, China. Intensified efforts were called to
      promote home smoking bans, especially for those with a lower education level,
      with lower income, and living in rural areas.

PMID- 24130144
TI  - Brief, instructional smokeless tobacco use among cigarette smokers who do not
      intend to quit: a pilot randomized clinical trial.
AB  - INTRODUCTION: Low-nitrosamine smokeless tobacco (SLT) may have efficacy for
      smoking reduction and cessation, but its public health impact depends on how
      smokers use it. METHODS: This pilot study explored brief, instructional low
      nitrosamine SLT use among smokers unmotivated to quit. Participants (N = 57) were
      randomized to either a free 2-week supply of Camel Snus group or a no-supply
      group. Of those randomized to use Camel Snus, half were told to use it to cope
      with smoking restrictions (Snus to Cope), and the remaining half were advised to
      use it to reduce smoking (Snus to Reduce). Participants were assessed before,
      during, and immediately after the intervention. RESULTS: Many Snus to Cope and
      Snus to Reduce participants reported daily use of Camel Snus, although the amount
      of use was low. Snus to Cope (18.4%) and Snus to Reduce (37.6%) participants
      reported a decline in number of cigarettes used per day, which was not reported
      by the control participants (p < .001). Intention to quit smoking and intention
      to quit all tobacco use (ps < .001) increased to a greater extent among Snus to
      Cope and Snus to Reduce participants than among control participants.
      CONCLUSIONS: This study replicates previous work that shows that low-nitrosamine
      SLT use can lead to reduced smoking and increased intention to quit, and it adds
      direct evidence to suggest that the function of low-nitrosamine SLT use-either to
      cope with smoking restrictions or to reduce smoking-can have a differential
      impact on smoking behavior. Overall, the results highlight the importance of
      messaging and, more specifically, marketing of low-nitrosamine SLT to smokers.

PMID- 24130145
TI  - Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone
      mineral density in postmenopausal Maya-Mestizo women.
AB  - OBJECTIVE: Osteoporosis is a complex disease characterized principally by low
      bone mineral density (BMD), which is determined by an interaction of genetic,
      metabolic, and environmental factors. The aim of this study was to analyze the
      possible association among one polymorphism of LRP5 and three polymorphisms of
      TNFRSF11B as well as their haplotypes with BMD variations in Maya-Mestizo
      postmenopausal women. METHODS: We studied 583 postmenopausal women of Maya
      Mestizo ethnic origin. A structured questionnaire for risk factors was applied
      and BMD was measured in lumbar spine (LS), total hip (TH), and femoral neck (FN)
      by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. One
      single-nucleotide polymorphism of LRP5 (rs3736228, p.A1330V) and three of
      TNFRSF11B (rs4355801, rs2073618, and rs6993813) were studied using real-time PCR
      allelic discrimination for genotyping. Differences between the means of the BMDs
      according to the genotype were analyzed with covariance. Deviations from Hardy
      Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single
      nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype
      analysis of TNFRSF11B was conducted. RESULTS: The Val genotype of the rs3736228
      (p.A1330V) of LRP5 was significantly associated with BMD variations at the LS,
      TH, and FN. None of the three polymorphisms of TNFRSF11B was associated with BMD
      variations. CONCLUSIONS: Our results show that p.A1330V was significantly
      associated with BMD variations at all three skeletal sites analyzed; the Val
      allele and the Val/Val genotype were those most frequently found in our
      population.

PMID- 24130146
TI  - Paravalvular leak closure for persisting aortic regurgitation after implantation
      of the CoreValve transcatheter valve.
AB  - Significant aortic regurgitation after TAVI results in lack of symptomatic and
      prognostic benefit from the procedure and generally requires intervention. While
      most of the regurgitations can be successfully targeted with standard techniques,
      occasional patients have restrictive calcification resistant to post-dilatation
      and significant regurgitation persists. We present a case of refractory aortic
      regurgitation successfully treated with percutaneous paravalvular leak closure.
      An 81-year-old man with symptomatic severe aortic stenosis underwent a
      transfemoral CoreValve TAVI in December 2009. He had significant aortic
      regurgitation refractory to medical and interventional therapy including balloon
      post-dilatation, valve repositioning and valve-in-valve reimplantation. Aortic
      regurgitation remained severe and therefore in early 2013, we proceeded with an
      attempted percutaneous closure of the residual paraprosthetic leak. Using 6
      French femoral access and a Terumo wire, the defect was successfully crossed with
      a 4-French Multipurpose catheter and an 8 mm Amplatzer Vascular Plug 4 device
      (St. Jude Medical) was deployed through this catheter, resulting in abolition of
      aortic regurgitation on aortography and TOE, with associated excellent clinical
      response. Refractory paravalvular aortic regurgitation post CoreValve
      implantation can be successfully treated using the Amplatzer Vascular Plug 4
      device.

PMID- 24130147
TI  - Tailored doxorubicin-hyaluronan conjugate as a potent anticancer glyco-drug: an
      alternative to prodrug approach.
AB  - Releasibility of doxorubicin from drug-conjugates is believed to be a
      prerequisite for its anti-cancer activity. Here, a new glyco-drug approach that
      circumvents the releasibility restriction is reported, opening a new possibility
      to design efficient, target specific drug delivery system. It is discovered that
      stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent
      cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to
      human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which
      express less CD44 receptor. This direct conjugation approach is an easy scalable
      strategy that could be adopted to design innocuous anti-tumor nanoparticle
      formulations. 

PMID- 24130148
TI  - Functional or somatoform disorders in Parkinson's disease?

PMID- 24130149
TI  - The microbiome of the paranasal sinuses has recently started to develop as a
      significant focus. Introduction.

PMID- 24130150
TI  - Copper(I)-catalyzed cycloaddition of bismuth(III) acetylides with organic azides:
      synthesis of stable triazole anion equivalents.
AB  - Fully loaded: Readily accessible and shelf-stable 1-bismuth(III) acetylides react
      rapidly and regiospecifically with organic azides in the presence of a copper(I)
      catalyst. The reaction tolerates many functional groups and gives excellent
      yields of the previously unreported 5-bismuth triazolides. This uniquely reactive
      intermediate is functionalized under mild reaction conditions to give fully
      substituted 1,2,3-triazoles. 

PMID- 24130151
TI  - Splice, insertion-deletion and nonsense mutations that perturb the phenylalanine
      hydroxylase transcript cause phenylketonuria in India.
AB  - Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by
      mutational inactivation of the phenylalanine hydroxylase (PAH) gene. Missense
      mutations are the most common PAH mutation type detected in PKU patients
      worldwide. We performed PAH mutation analysis in 27 suspected Indian PKU families
      (including 7 from our previous study) followed by structure and function analysis
      of specific missense and splice/insertion-deletion/nonsense mutations,
      respectively. Of the 27 families, disease-causing mutations were detected in 25.
      A total of 20 different mutations were identified of which 7 "unique" mutations
      accounted for 13 of 25 mutation positive families. The unique mutations detected
      exclusively in Indian PKU patients included three recurrent mutations detected in
      three families each. The 20 mutations included only 5 missense mutations in
      addition to 5 splice, 4 each nonsense and insertion-deletion mutations, a silent
      variant in coding region and a 3'UTR mutation. One deletion and two nonsense
      mutations were characterized to confirm significant reduction in mutant
      transcript levels possibly through activation of nonsense mediated decay. All
      missense mutations affected conserved amino acid residues and sequence and
      structure analysis suggested significant perturbations in the enzyme activity of
      respective mutant proteins. This is probably the first report of identification
      of a significantly low proportion of missense PAH mutations from PKU families and
      together with the presence of a high proportion of splice, insertion-deletion,
      and nonsense mutations, points to a unique PAH mutation profile in Indian PKU
      patients.

PMID- 24130152
TI  - Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes.
AB  - A 0.8 kb intronic duplication in MAGT1 and a single base pair deletion in the
      last exon of ATRX were identified using a chromosome X-specific microarray and
      exome sequencing in a family with five males demonstrating intellectual
      disability (ID) and unusual skin findings (e.g., generalized pruritus). MAGT1 is
      an Mg2+ transporter previously associated with primary immunodeficiency and ID,
      whereas mutations in ATRX cause ATRX-ID syndrome. In patient cells, the function
      of ATRX was demonstrated to be abnormal based on altered RNA/protein expression,
      hypomethylation of rDNA, and abnormal cytokinesis. Dysfunction of MAGT1 was
      reflected in reduced RNA/protein expression and Mg2+ influx. The mutation in ATRX
      most likely explains the ID, whereas MAGT1 disruption could be linked to abnormal
      skin findings, as normal magnesium homeostasis is necessary for skin health. This
      work supports observations that multiple mutations collectively contribute to the
      phenotypic variability of syndromic ID, and emphasizes the importance of
      correlating clinical phenotype with genomic and cell function analyses.

PMID- 24130154
TI  - Journal policy on research funded by the tobacco industry.

PMID- 24130153
TI  - Altered gene expression patterns in muscle ring finger 1 null mice during
      denervation- and dexamethasone-induced muscle atrophy.
AB  - Muscle atrophy can result from inactivity or unloading on one hand or the
      induction of a catabolic state on the other. Muscle-specific ring finger 1
      (MuRF1), a member of the tripartite motif family of E3 ubiquitin ligases, is an
      essential mediator of multiple conditions inducing muscle atrophy. While most
      studies have focused on the role of MuRF1 in protein degradation, the protein may
      have other roles in regulating skeletal muscle mass and metabolism. We therefore
      systematically evaluated the effect of MuRF1 on gene expression during
      denervation and dexamethasone-induced atrophy. We find that the lack of MuRF1
      leads to few differences in control animals, but there were several significant
      differences in specific sets of genes upon denervation- and dexamethasone-induced
      atrophy. For example, during denervation, MuRF1 knockout mice showed delayed
      repression of metabolic and structural genes and blunted induction of genes
      associated with the neuromuscular junction. In the latter case, this pattern
      correlates with blunted HDAC4 and myogenin upregulation. Lack of MuRF1 caused
      fewer changes in the dexamethasone-induced atrophy program, but certain genes
      involved in fat metabolism and intracellular signaling were affected. Our results
      demonstrate a new role for MuRF1 in influencing gene expression in two important
      models of muscle atrophy. 

PMID- 24130156
TI  - The C-terminal extension of human RTEL1, mutated in Hoyeraal-Hreidarsson
      syndrome, contains harmonin-N-like domains.
AB  - Several studies have recently shown that germline mutations in RTEL1, an
      essential DNA helicase involved in telomere regulation and DNA repair, cause
      Hoyeraal-Hreidarsson syndrome (HHS), a severe form of dyskeratosis congenita.
      Using original new softwares, facilitating the delineation of the different
      domains of the protein and the identification of remote relationships for orphan
      domains, we outline here that the C-terminal extension of RTEL1, downstream of
      its catalytic domain and including several HHS-associated mutations, contains a
      yet unidentified tandem of harmonin-N-like domains, which may serve as a hub for
      partner interaction. This finding highlights the potential critical role of this
      region for the function of RTEL1 and gives insights into the impact that the
      identified mutations would have on the structure and function of these domains.

PMID- 24130155
TI  - Non-invasive and in situ characterization of the degradation of biomaterial
      scaffolds by volumetric photoacoustic microscopy.
AB  - Degradation is among the most important properties of biomaterial scaffolds,
      which are indispensable for regenerative medicine. The currently used method
      relies on the measurement of mass loss across different samples and cannot track
      the degradation of an individual scaffold in situ. Here we report, for the first
      time, the use of multiscale photoacoustic microscopy to non-invasively monitor
      the degradation of an individual scaffold. We could observe alterations to the
      morphology and structure of a scaffold at high spatial resolution and deep
      penetration, and more significantly, quantify the degradation of an individual
      scaffold as a function of time, both in vitro and in vivo. In addition, the
      remodeling of vasculature inside a scaffold can be visualized simultaneously
      using a dual-wavelength scanning mode in a label-free manner. This optoacoustic
      method can be used to monitor the degradation of individual scaffolds, offering a
      new approach to non-invasively analyze and quantify biomaterial-tissue
      interactions in conjunction with the assessment of in vivo vascular parameters. 

PMID- 24130157
TI  - Insect host-parasite coevolution in the light of experimental evolution.
AB  - The many ways parasites can impact their host species have been the focus of
      intense study using a range of approaches. A particularly promising but under
      used method in this context is experimental evolution, because it allows targeted
      manipulation of known populations exposed to contrasting conditions. The strong
      potential of applying this method to the study of insect hosts and their
      associated parasites is demonstrated by the few available long-term experiments
      where insects have been exposed to parasites. In this review, we summarize these
      studies, which have delivered valuable insights into the evolution of resistance
      in response to parasite pressure, the underlying mechanisms, as well as
      correlated genetic responses. We further assess findings from relevant artificial
      selection studies in the interrelated contexts of immunity, life history, and
      reproduction. In addition, we discuss a number of well-studied Tribolium
      castaneum-Nosema whitei coevolution experiments in more detail and provide
      suggestions for research. Specifically, we suggest that future experiments should
      also be performed using nonmodel hosts and should incorporate contrasting
      experimental conditions, such as population sizes or environments. Finally, we
      expect that adding a third partner, for example, a second parasite or symbiont,
      to a host-parasite system could strongly impact (co)evolutionary dynamics. 

PMID- 24130158
TI  - First in vivo evaluation of a flexible self-apposing left atrial appendage
      closure device in the canine model.
AB  - OBJECTIVES: Aimed to evaluate the feasibility of deployment and healing response
      of a novel transcatheter left atrial appendage (LAA) occlusion device in the
      canine model BACKGROUND: LAA occlusion is proposed to reduce the risk of stroke
      in atrial fibrillation patients METHODS: Transseptal puncture and device
      deployment was guided under fluoroscopy and transesophageal echocardiography
      (TEE) in five dogs. First, a distal cylindrical bulb occluder was released and
      secured to the appendage wall with hooks. Subsequently, a proximal sail was
      unfolded, covering the LAA ostium. Rotational angiography, TEE, and histology
      outcomes were assessed 30 days following implantation RESULTS: Pre-operative TEE
      revealed the mean diameter of the LAA ostium to be 17.2 +/- 1.6 mm with a depth
      of 18.5 +/- 1.7 mm. The landing zone for the distal bulb was measured to be 12.8
      +/- 1.3 mm. The mean bulb diameter at implant was 16.8 +/- 1.8 mm. Post-operative
      TEE showed adequate positioning and successful LAA occlusion with all implanted
      devices. Pericardial effusion requiring pericardiocentesis was seen in one animal
      following device implantation. At 30 days, TEE revealed full occlusion of all LAA
      ostia with the exception of a minimal peri-device leak (<3 mm) observed in one
      animal. No pericardial effusion or device-related thrombus formation was found at
      termination. Histological analysis confirmed circumferential occlusion of all
      appendages and complete neointimal coverage on the luminal aspect of the occluder
      CONCLUSION: The percutaneous delivery of a novel self-positioning LAA occlusion
      device is feasible and safe in a canine model. At 30 days, all devices displayed
      complete healing and occlusion of the LAA without any device related adverse
      events.

PMID- 24130159
TI  - Plant purine nucleoside catabolism employs a guanosine deaminase required for the
      generation of xanthosine in Arabidopsis.
AB  - Purine nucleotide catabolism is common to most organisms and involves a guanine
      deaminase to convert guanine to xanthine in animals, invertebrates, and
      microorganisms. Using metabolomic analysis of mutants, we demonstrate that
      Arabidopsis thaliana uses an alternative catabolic route employing a highly
      specific guanosine deaminase (GSDA) not reported from any organism so far. The
      enzyme is ubiquitously expressed and deaminates exclusively guanosine and 2'
      deoxyguanosine but no other aminated purines, pyrimidines, or pterines. GSDA
      belongs to the cytidine/deoxycytidylate deaminase family of proteins together
      with a deaminase involved in riboflavin biosynthesis, the chloroplastic tRNA
      adenosine deaminase Arg and a predicted tRNA-specific adenosine deaminase 2 in A.
      thaliana. GSDA is conserved in plants, including the moss Physcomitrella patens,
      but is absent in the algae and outside the plant kingdom. Our data show that
      xanthosine is exclusively generated through the deamination of guanosine by GSDA
      in A. thaliana, excluding other possible sources like the dephosphorylation of
      xanthosine monophosphate. Like the nucleoside hydrolases NUCLEOSIDE HYDROLASE1
      (NSH1) and NSH2, GSDA is located in the cytosol, indicating that GMP catabolism
      to xanthine proceeds in a mostly cytosolic pathway via guanosine and xanthosine.
      Possible implications for the biosynthetic route of purine alkaloids (caffeine
      and theobromine) and ureides in other plants are discussed. 

PMID- 24130161
TI  - Intergrowth structure and aluminium zoning of a zeolite ZSM-5 crystal as resolved
      by synchrotron-based micro X-ray diffraction imaging.

PMID- 24130162
TI  - Mini-scale cultivation method enables expeditious plasmid production in
      Escherichia coli.
AB  - The standard procedure in the lab for plasmid isolation usually involves a 2-mL,
      16 h over-night cultivation in 15-mL bioreaction tubes in LB medium. This is time
      consuming, and not suitable for high-throughput applications. This study shows
      that it is possible to produce plasmid DNA (pDNA) in a 1.5-mL microcentrifuge
      tube with only 100 MUL cultivation volume in less than 7 h with a simple
      protocol. Compared with the standard LB cultivation for pDNA production reaching
      a final pDNA concentration range of 1.5-4 MUg mL(-1), a 6- to 10-fold increase in
      plasmid concentration (from 10 up to 25 MUg mL(-1) cultivation volume) is
      achieved using an optimized medium with an internal substrate delivery system
      (EnBase(r)). Different strains, plasmids, and the applicability of different
      inoculation tools (i.e. different starting ODs) were compared, demonstrating the
      robustness of the system. Additionally, dissolved oxygen was monitored in real
      time online, indicating that under optimized conditions oxygen limitation can be
      avoided. We developed a simple protocol with a significantly decreased procedure
      time, enabling simultaneous handling of more samples, while a consistent quality
      and a higher final pDNA concentration are ensured.

PMID- 24130163
TI  - Coping behaviours and post-traumatic stress in war-affected eastern Congolese
      adolescents.
AB  - This study explores coping strategies used by war-affected eastern Congolese
      adolescents across age and sex, and the association between post-traumatic stress
      symptoms and engagement and disengagement coping. Cross-sectional data were
      collected in 11 secondary schools across four areas in the Ituri province,
      Democratic Republic of Congo. A total of 952 pupils (45.3% girls, 54.7% boys)
      aged 13-21 years (M = 15.83, standard deviation = 1.81) participated in self
      report assessment, using instruments that were either specifically developed
      (Adolescent Complex Emergency Exposure Scale, assessing traumatic exposure),
      validated (Impact of Event Scale Revised, assessing post-traumatic stress
      symptoms) or reviewed (Kidcope, assessing coping strategies) for the study
      population. Reported coping strategies varied with age, and boys more frequently
      reported problem solving and resignation as compared with girls. Disengagement
      coping was associated with lower symptom scores in younger adolescent girls, as
      was the interaction effect between engagement and disengagement coping. We
      conclude that disengagement coping is not necessarily a maladaptive reaction to
      stressful events in war-affected situations and that future research should aim
      to better understand the heterogeneous patterns of stress and coping responses,
      including the role of factors such as the nature and appraisal of stressors,
      available resources for coping and cultural preferences.

PMID- 24130164
TI  - Heat shock factor 1 accelerates hepatocellular carcinoma development by
      activating nuclear factor-kappaB/mitogen-activated protein kinase.
AB  - Heat shock factor 1 (HSF1), a major transactivator of stress responses, has been
      implicated in carcinogenesis in various organs. However, little is known about
      the biological functions of HSF1 in the development of hepatocellular carcinoma
      (HCC). To clarify the functional role of HSF1 in HCC, we established HSF1
      knockdown (HSF1 KD) KYN2 HCC cells by stably expressing either small hairpin RNA
      (shRNA) against HSF1 (i.e. HSF1 KD) or control shRNA (HSF1 control).
      Tumorigenicity was significantly reduced in orthotopic mice with HSF1 KD cells
      compared with those with HSF1 control cells. Reduced tumorigenesis in HSF1 KD
      cells appeared attributable to increased apoptosis and decreased proliferation.
      Tumor necrosis factor-alpha-induced apoptosis was increased in HSF1 KD cells and
      HSF1(-/-) mouse hepatocytes compared with controls. Decreased expression of
      IkappaB kinase gamma, a positive regulator of nuclear factor-kappaB, was also
      observed in HSF1 KD cells and HSF1(-/-) mouse hepatocytes. Furthermore,
      expression of bcl-2-associated athanogene domain 3 (BAG3) was dramatically
      reduced in HSF1 KD cells and HSF1(-/-) mouse hepatocytes. We also found that
      epidermal growth factor-stimulated mitogen-activated protein kinase signaling was
      impaired in HSF1 KD cells. Clinicopathological analysis demonstrated frequent
      overexpression of HSF1 in human HCCs. Significant correlations between HSF1 and
      BAG3 protein levels and prognosis were also observed. In summary, these results
      identify a mechanistic link between HSF1 and liver tumorigenesis and may provide
      as a potential molecular target for the development of anti-HCC therapies. 

PMID- 24130165
TI  - Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant
      transformation and chemotherapy resistance.
AB  - Simian virus 40 (SV40) has been implicated in the development of several cancers
      including malignant mesothelioma. A definitive role for the virus in human
      mesothelioma has not been unequivocally demonstrated but has been rigorously
      debated. The virus clearly has oncogenic potential: the TAg is one of the most
      potent transforming proteins known and acts synergistically with crocidolite
      asbestos to transform mesothelial cells. In this study, we show that SV40
      oncogenes alone can cause malignant transformation and that asbestos-induced DNA
      damage and apoptosis occurs principally in cycling cells. After long-term
      exposure (up to 100 days) to both SV40 and asbestos, cells become resistant to
      stress-induced senescence. Significantly, these cells demonstrate resistance to
      chemotherapy-induced apoptosis. This finding has implications for the development
      of effective treatment options for patients with mesothelioma. 

PMID- 24130166
TI  - MYCN and survivin cooperatively contribute to malignant transformation of
      fibroblasts.
AB  - The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse
      cancers including sarcomas. To investigate whether these oncogenes cooperate in
      initial malignant transformation, we transduced them into Rat-1 fibroblasts.
      Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage
      independent growth in vitro. Importantly, upon subcutaneous transplantation into
      mice, cells overexpressing both instead of either one of the oncogenes generated
      tumors with shortened latency, marked anaplasia and an increased proliferation-to
      apoptosis ratio resulting in accelerated growth. Mechanistically, the increased
      tumorigenicity was associated with an enhanced Warburg effect and a hypoxia
      inducible factor 1alpha linked vascular remodeling. This cooperation between MYCN
      and survivin may be important in the genesis of several cancers. 

PMID- 24130167
TI  - Metformin targets c-MYC oncogene to prevent prostate cancer.
AB  - Prostate cancer (PCa) is the second leading cause of cancer-related death in
      American men and many PCa patients develop skeletal metastasis. Current treatment
      modalities for metastatic PCa are mostly palliative with poor prognosis.
      Epidemiological studies indicated that patients receiving the diabetic drug
      metformin have lower PCa risk and better prognosis, suggesting that metformin may
      have antineoplastic effects. The mechanism by which metformin acts as
      chemopreventive agent to impede PCa initiation and progression is unknown. The
      amplification of c-MYC oncogene plays a key role in early prostate epithelia cell
      transformation and PCa growth. The purpose of this study is to investigate the
      effect of metformin on c-myc expression and PCa progression. Our results
      demonstrated that (i) in Hi-Myc mice that display murine prostate neoplasia and
      highly resemble the progression of human prostate tumors, metformin attenuated
      the development of prostate intraepithelial neoplasia (PIN, the precancerous
      lesion of prostate) and PCa lesions. (ii) Metformin reduced c-myc protein levels
      in vivo and in vitro. In Myc-CaP mouse PCa cells, metformin decreased c-myc
      protein levels by at least 50%. (iii) Metformin selectively inhibited the growth
      of PCa cells by stimulating cell cycle arrest and apoptosis without affecting the
      growth of normal prostatic epithelial cells (RWPE-1). (iv) Reduced PIN formation
      by metformin was associated with reduced levels of androgen receptor and
      proliferation marker Ki-67 in Hi-Myc mouse prostate glands. Our novel findings
      suggest that by downregulating c-myc, metformin can act as a chemopreventive
      agent to restrict prostatic neoplasia initiation and transformation. SUMMARY:
      Metformin, an old antidiabetes drug, may inhibit prostate intraepithelial
      neoplasia transforming to cancer lesion via reducing c-MYC, an 'old'
      overexpressed oncogene. This study explores chemopreventive efficacy of metformin
      in prostate cancer and its link to cMYC in vitro and in vivo.

PMID- 24130168
TI  - Characterization of microRNA-29 family expression and investigation of their
      mechanistic roles in gastric cancer.
AB  - Increasing evidence shows that abnormal microRNAs (miRNAs) expression is involved
      in tumorigenesis. They might be the novel biomarkers or therapeutic targets in
      disease treatment. miR-29 family was previously reported to act as tumor
      suppressors or oncogenes in diverse cancers. However, their accurate expression,
      function and mechanism in gastric cancer (GC) are not well known. Here, we found
      that the expression of miR-29 family members was significantly reduced in GC
      compared with adjacent controls. Among them, miR-29c had the most reduced
      percentage in GC and was associated with aggressive and progressive phenotypes of
      GC. We further demonstrated that miR-29 family acted as tumor suppressors through
      targeting CCND2 and matrix metalloproteinase-2 genes in GC. Moreover, the inverse
      relationship between miR-29 family and their targets was verified in patients and
      xenograft mice. Finally, reintroduction of miR-29 family significantly inhibited
      tumor formation of GC cells in the xenograft mice. Take together, our finding
      characterized the expression properties of miR-29 family, contributed to the
      function and molecular mechanism of miR-29 family in GC and implied that miR-29
      family might be employed as novel prognostic markers and therapeutic targets of
      GC. 

PMID- 24130169
TI  - ZEB2-Sp1 cooperation induces invasion by upregulating cadherin-11 and integrin
      alpha5 expression.
AB  - Epithelial-mesenchymal transition (EMT) is a process implicated in invasion and
      metastasis. EMT is characterized by repression of epithelial markers and
      induction of mesenchymal markers. ZEB2 is a transcriptional repressor of E
      cadherin, leading to EMT. Previously, we have shown that ZEB2 directly
      upregulates integrin alpha5 transcription by cooperating with the transcription
      factor Sp1. In this study, we investigated the precise mechanism by which ZEB2
      modulates invasion and EMT events and the role of Sp1 in ZEB2-induced invasion.
      We found that ZEB2 directly induced cadherin-11 transcription in an Sp1
      dependent, but Smad- and E-box-independent, manner and repressed E-cadherin
      expression in an Sp1- and Smad-independent manner, leading to cadherin switch.
      Furthermore, ZEB2 upregulated Sp1 by enhancing Sp1 protein stability, and Sp1 was
      found to be critical for ZEB2-induced cancer cell invasion, mainly through
      induction of cadherin-11 and integrin alpha5. Expression levels of cadherin-11
      and integrin alpha5 were interdependent and both modulated c-Jun N-terminal
      kinase-signaling activity and invasion. Immunofluorescence analysis showed that
      nuclear expression of ZEB2 was positively correlated with Sp1 expression in human
      colorectal cancers. Together, these findings demonstrate a previously
      unrecognized interplay between ZEB2, Sp1, cadherin-11 and integrin alpha5 that
      is, probably, significant in tumor progression and metastasis. 

PMID- 24130170
TI  - SH3RF2 functions as an oncogene by mediating PAK4 protein stability.
AB  - SH3RF (SH3-domain-containing RING finger protein) family members, SH3RF1-3, are
      multidomain scaffold proteins involved in promoting cell survival and apoptosis.
      In this report, we show that SH3RF2 is an oncogene product that is overexpressed
      in human cancers and regulates p21-activated kinase 4 (PAK4) protein stability.
      Immunohistochemical analysis of 159 colon cancer tissues showed that SH3RF2
      expression levels are frequently elevated in cancer tissues and significantly
      correlate with poor prognostic indicators, including increased invasion, early
      recurrence and poor survival rates. We also demonstrated that PAK4 protein is
      degraded by the ubiquitin-proteasome system and that SH3RF2 inhibits PAK4
      ubiquitination via physical interaction-mediated steric hindrance, which results
      in the upregulation of PAK4 protein. Moreover, ablation of SH3RF2 expression
      attenuates TRADD (TNFR-associated death domain) recruitment to tumor necrosis
      factor-alpha (TNF-alpha) receptor 1 and hinders downstream signals, thereby
      inhibiting NF-kappaB (nuclear factor-kappaB) activity and enhancing caspase-8
      activity, in the context of TNF-alpha treatment. Notably, ectopic expression of
      SH3RF2 effectively prevents apoptosis in cancer cells and enhances cell
      migration, colony formation and tumor growth in vivo. Taken together, our results
      suggest that SH3RF2 is an oncogene that may be a definitive regulator of PAK4.
      Therefore, SH3RF2 may represent an effective therapeutic target for cancer
      treatment.

PMID- 24130171
TI  - Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk
      of breast cancer in the Sister Study.
AB  - Global decrease in DNA methylation is a common feature of cancer and is
      associated with genomic and chromosomal instability. Retrospective case-control
      studies have reported that cancer patients have lower global methylation levels
      in blood DNA than do controls. We used prospectively collected samples and a case
      cohort study design to examine global DNA methylation and incident breast cancer
      in 294 cases and a sample of 646 non-cases in the Sister Study, a study of 50 884
      women aged 35-74 years who had not been diagnosed with breast cancer at the time
      of blood draw. Global methylation in DNA from peripheral blood was assessed by
      pyrosequencing of the LINE-1 repetitive element. Quartiles of LINE-1 methylation
      levels were associated with the risk of breast cancer in a dose-dependent fashion
      (P, trend = 0.002), with an increased risk observed among women in the lowest
      quartile compared with those in the highest quartile (hazard ratio = 1.75; 95%
      confidence interval 1.19, 2.59). We also examined 22 polymorphisms in 10 one
      carbon metabolism genes in relation to both LINE-1 methylation levels and breast
      cancer. We found three single-nucleotide polymorphisms in those genes associated
      with LINE-1 methylation: SLC19A1 (rs1051266); MTRR (rs10380) and MTHFR
      (rs1537514), one of which was also associated with breast cancer risk: MTHFR
      (rs1537514). PON1 (rs757158) was associated with breast cancer but not
      methylation. 

PMID- 24130172
TI  - Prognostic significance of KAI1/CD82 in human melanoma and its role in cell
      migration and invasion through the regulation of ING4.
AB  - KAI1/CD82 is a member of the transmembrane 4 superfamily, which was first
      identified as a metastasis suppressor for prostate cancer. The expression of KAI1
      was found to be reduced in many types of cancers, including prostate, breast,
      ovarian, cervical and endometrial cancer. However, the role of KAI1 in melanoma
      pathogenesis is not known. In this study, we investigated the expression level of
      KAI1 in a large set of melanocytic lesions at different stages. We found that the
      expression of KAI1 is significantly decreased during melanoma progression. In
      fact, KAI1 expression is drastically reduced in primary melanoma compared with
      dysplastic nevi (P = 1.8*10(-4)) and further reduced in metastatic melanoma
      compared with primary melanoma (P = 9.4 * 10(-15)). Furthermore, decreased KAI1
      staining is strongly correlated with a worse 5 year and 10 year patient survival.
      Multivariate Cox regression analysis showed that KAI1 is also an independent
      prognostic factor for both 5 year and 10 year survival. Moreover, we found that
      overexpression of KAI1 significantly inhibited melanoma cell migration through
      suppression of Rho-associated kinase-mediated formation of stress fiber. Our data
      also suggested that overexpression of KAI1 significantly inhibited melanoma cell
      invasion by reducing the activity of metalloproteinase-2. In addition, we found
      that suppression of melanoma cell migration by KAI1 is mediated by another tumor
      suppressor protein called inhibitor of growth 4 through the regulation of p65.
      Taken together, our data suggest that KAI1 may be used as a promising prognostic
      marker and a possible therapeutic target for human melanoma. 

PMID- 24130174
TI  - Copper-mediated synthesis of 1,2,3-triazoles from N-tosylhydrazones and anilines.

PMID- 24130173
TI  - Expression of human butyrylcholinesterase with an engineered glycosylation
      profile resembling the plasma-derived orthologue.
AB  - Human butyrylcholinesterase (BChE) is considered a candidate bioscavenger of
      nerve agents for use in pre- and post-exposure treatment. However, the presence
      and functional necessity of complex N-glycans (i.e. sialylated structures) is a
      challenging issue in respect to its recombinant expression. Here we transiently
      co-expressed BChE cDNA in the model plant Nicotiana benthamiana with vectors
      carrying the genes necessary for in planta protein sialylation. Site-specific
      sugar profiling of secreted recombinant BChE (rBChE) collected from the
      intercellular fluid revealed the presence of mono- and di-sialylated N-glycans,
      which largely resembles to the plasma-derived orthologue. Attempts to increase
      that sialylation content of rBChE by the over-expression of an additional
      glycosylation enzyme that generates branched N-glycans (i.e. beta1,4-N
      acetylglucosaminyl-transferase IV), allowed the production of rBChE decorated
      with tri-sialylated structures (up to 70%). Sialylated and non-sialylated plant
      derived rBChE exhibited functional in vitro activity comparable to that of its
      commercially available equine-derived counterpart. These results demonstrate the
      ability of plants to generate valuable proteins with designed sialylated
      glycosylation profiles optimized for therapeutic efficacy. Moreover, the
      efficient synthesis of carbohydrates present only in minute amounts on the native
      protein (tri-sialylated N-glycans) facilitates the generation of a product with
      superior efficacies and/or new therapeutic functions. 

PMID- 24130175
TI  - Synthesis, characterization, and metabolism studies of fluspidine enantiomers.
AB  - The enantiomers of the potent sigma1 ligand fluspidine (1) were prepared by using
      chiral preparative HPLC. Synthesis of racemic tosylate 2 and subsequent
      separation of enantiomers yielded (R)-2 and (S)-2 in excellent enantiomeric
      purities. The fluspidine enantiomers (R)-1 and (S)-1 were synthesized from (R)-2
      and (S)-2 by nucleophilic substitution with tetra-n-butylammonium fluoride,
      affording (R)-1 with 99.6 % ee and (S)-1 with 96.4 % ee. Tosylates (R)-2 and (S)
      2 can also serve as precursors for the radiosynthesis of enantiomerically pure
      radiotracers [(18) F](R)-1 and [(18) F](S)-1. The absolute configuration of the
      pure enantiomers was elucidated by comparison of their CD spectra with a
      calculated CD spectrum of a simplified model compound. In receptor binding
      studies, both enantiomers displayed very high sigma1 receptor affinity and
      selectivity against the sigma2 receptor. (R)-Fluspidine ((R)-1) is the eutomer,
      with a Ki value of 0.57 nM and a eudysmic ratio of 4. Incubation of (R)-1 and (S)
      1 with rat liver microsomes led to the identification of seven and eight
      metabolites, respectively. Although the S-configured enantiomer formed additional
      metabolite (S)-1-3, it is metabolically more stable than (R)-1. 

PMID- 24130176
TI  - 1,2-naphthoquinone stimulates lipid peroxidation and cholesterol domain formation
      in model membranes.
AB  - PURPOSE: Naphthalene induces cataract formation through the accumulation of its
      reactive metabolite, 1,2-naphthoquinone (1,2-NQ), in the ocular lens. 1,2-NQ
      increases lens protein oxidation and disrupts fiber cell membrane function;
      however, the association of these effects with changes in membrane structure is
      not understood. The goal of this study was to determine the direct effects of 1,2
      NQ on membrane lipid oxidation and structural organization. METHODS: Iodometric
      approaches were used to measure the effects of naphthalene and 1,2-NQ on lipid
      hydroperoxide (LOOH) formation in model membranes composed of cholesterol and
      dilinoleoylphosphatidylcholine. Membrane samples were prepared at various
      cholesterol-to-phospholipid mole ratios and subjected to autoxidation at 37
      degrees C for 48 hours in the absence or presence of either agent alone (0.1-5.0
      MUM) or in combination with vitamin E. Small-angle x-ray diffraction was used to
      measure the effects of naphthalene and 1,2-NQ on membrane structure before and
      after exposure to oxidative stress. RESULTS: 1,2-NQ increased LOOH formation by
      250% (P < 0.001) and 350% (P < 0.001) at 1.0 and 5.0 MUM, respectively, whereas
      naphthalene decreased LOOH levels by 25% (P < 0.01) and 10% (NS). The pro-oxidant
      effect of 1,2-NQ was inversely affected by membrane cholesterol enrichment and
      completely blocked by vitamin E. 1,2-NQ also increased cholesterol domain
      formation by 360% in membranes exposed to oxidative stress; however, no
      significant changes in membrane lipid organization were observed with naphthalene
      under the same conditions. CONCLUSIONS: These data suggest a novel mechanism for
      naphthalene-induced cataract, facilitated by the direct effects of 1,2-NQ on
      lipid peroxidation and cholesterol domain formation.

PMID- 24130177
TI  - Waveform analysis of ocular blood flow and the early detection of normal tension
      glaucoma.
AB  - PURPOSE: To investigate waveform changes in blood flow (BF) in the optic nerve
      head (ONH) and to evaluate their usefulness in identifying normal tension
      glaucoma (NTG). METHODS: Sixty-one eyes of 61 patients with NTG and 21 eyes of
      age-matched healthy control subjects were included in this study. The NTG eyes
      were divided into the following three groups based on the progression of their
      visual field defects: mild (mean deviation [MD] greater than -6.0 decibels [dB]),
      moderate (MD between -6.0 and -12.0 dB), and severe (MD less than -12.0 dB). The
      ONH BF analysis was performed with laser speckle flowgraphy (LSFG) and included
      waveform variables such as skew, acceleration time index (ATI), and blowout time.
      RESULTS: In the ONH, LSFG skew variables were significantly lower in the NTG eyes
      than in the control eyes (P < 0.001), and ATI was significantly higher (P <
      0.01), despite similar systemic characteristics in the four groups. The
      differences were most marked in the mild NTG group. Multiple linear regression
      analysis showed that MD, average thickness of the circumpapillary retinal nerve
      fiber layer, and pulse rate were predictive factors for both skew and ATI. A
      receiver operating characteristic (ROC) curve analysis also revealed that skew
      (area under the ROC curve, 0.89) and ATI (area under the ROC curve, 0.80) had the
      greatest power to differentiate normal eyes from eyes with mild NTG. CONCLUSIONS:
      These results suggest that LSFG measurements of waveform changes in ONH BF can
      differentiate healthy eyes from eyes with NTG, particularly those with mild NTG.

PMID- 24130178
TI  - Ocular phenotype of Fbn2-null mice.
AB  - PURPOSE: Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during
      development of the mouse eye. To test its role in morphogenesis, we examined the
      ocular phenotype of Fbn2(-/-) mice. METHODS: Ocular morphology was assessed by
      confocal microscopy using antibodies against microfibril components. RESULTS:
      Fbn2(-/-) mice had a high incidence of anterior segment dysgenesis. The iris was
      the most commonly affected tissue. Complete iridal coloboma was present in 37% of
      eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined
      incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent
      in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence
      of Fbn2 was partially compensated for by increased expression of fibrillin-1,
      although the resulting PM microfibrils were disorganized, compared with WTs. In
      colobomatous adult Fbn2(-/-) eyes, the PM failed to regress normally, especially
      beneath the notched region of the iris. Segments of the ciliary body were
      hypoplastic, and zonular fibers, although relatively plentiful, were unevenly
      distributed around the lens equator. In regions where the zonular fibers were
      particularly disturbed, the synchronous differentiation of the underlying lens
      fiber cells was affected. CONCLUSIONS: Fbn2 has an indispensable role in ocular
      morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals
      implies a previously unsuspected role in optic fissure closure. The observation
      that fiber cell differentiation was disturbed in Fbn2(-/-) mice raises the
      possibility that the attachment of zonular fibers to the lens surface may help
      specify the equatorial margin of the lens epithelium.

PMID- 24130179
TI  - Regulation of endothelial progenitor cell release by Wnt signaling in bone
      marrow.
AB  - PURPOSE: Endothelial progenitor cells (EPC) have been shown to participate in
      ischemia-induced retinal neovascularization (NV). Overactivation of Wnt signaling
      has a pathogenic role in ischemia-induced retinal NV. The purpose of this study
      is to determine whether Wnt signaling regulates EPC release. METHODS: Oxygen
      induced retinopathy (OIR) was used as a model of retinal NV and Wnt pathway
      activation. The EPC, marked as c-Kit(+)/Tie-2(+) cells in the peripheral blood
      and bone marrow, were quantified using flow cytometry following immunolabeling.
      The Wnt signaling activity was evaluated by measuring nonphosphorylated beta
      catenin levels and X-gal staining in the Wnt reporter mice (Bat-gal mice).
      RESULTS: The c-Kit(+)/Tie-2(+) cells were increased significantly in the
      peripheral blood and bone marrow of mice with OIR, compared to non-OIR mice.
      Overexpression of kallistatin, an endogenous inhibitor of the Wnt pathway, in
      kallistatin transgenic (kallistatin-TG) mice with OIR attenuated the increases of
      c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, compared to WT
      mice with OIR. When the Bat-gal mice were crossed with kallistatin-TG mice,
      kallistatin overexpression suppressed the OIR-induced increases of X-gal-positive
      cells in the retinas and bone marrow, suggesting inhibition of Wnt signaling in
      these tissues. Furthermore, intraperitoneal injection of LiCl, a Wnt signaling
      activator, increased c-Kit(+)/Tie-2(+) cells in the peripheral blood of normal
      mice. Consistently, LiCl activated Wnt signaling in the retina and bone marrow
      cells in Bat-gal mice. CONCLUSIONS: The Wnt signaling pathway has an important
      role in EPC release during retinal NV in OIR.

PMID- 24130181
TI  - Novel heavy tamponade for vitreoretinal surgery.
AB  - PURPOSE: The aim of this study was to produce a heavy tamponade with a specific
      gravity greater than 1.06 g/mL that was optically transparent, could be
      manufactured using simple processing, could be injected using standard clinical
      equipment, and would have appropriate biocompatibility. METHODS: Aerosil silica
      was added to a phenyl trimethicone and mixed via a roller, overhead stirring, and
      ultrasonics. The refractive index, visible absorbance, and shear viscosity were
      measured. The injectability of the solutions was evaluated using the Accurus
      Viscous Fluid Injection system. The tamponade efficiency was assessed using a
      model eye chamber and compared with that of Densiron 68, Oxane HD, and F6H8. The
      biocompatibility was evaluated in vitro and in vivo in rabbits. RESULTS:
      Tamponade agents were produced with specific gravities of 1.10, 1.11, 1.13, and
      1.16 g/mL that had good optical clarity. Mixing using overhead stirring was
      sufficient to produce tamponade agents with shear viscosities in the range 1000
      to 5000 mPa.s that were reproducible and stable during storage. The solutions
      were easier to inject using the Accurus Viscous Fluid Injection system than
      silicone oil 1000 mPa.s. The 11% silica solution had greater tamponade efficiency
      than Densiron 68 or Oxane HD. There was no evidence of cytotoxicity in vitro.
      Silica solution 11% induced cataract earlier than Polydimethylsiloxane 1000 (PDMS
      1000). Silica solution 11% and phenyl trimethicone reduced the a-wave value at 1
      week after vitrectomy, but recovery was observed at later time points. Silica
      solution 11% caused inner nuclear layer (INL) nuclei dropdown in inferior retina
      from 4 weeks postoperation. Polydimethylsiloxane 1000 induced a similar
      phenomenon in superior retina 12 weeks postoperation. CONCLUSIONS: We have
      produced a heavy tamponade with good clarity that has appropriate shear
      viscosity, injectibility, enhanced tamponade efficiency, and biocompatibility
      similar to that of PDMS 1000.

PMID- 24130180
TI  - Interferon regulatory factor-1 in flagellin-induced reprogramming: potential
      protective role of CXCL10 in cornea innate defense against Pseudomonas aeruginosa
      infection.
AB  - PURPOSE: We previously showed that pre-exposure of the cornea to Toll-like
      receptor (TLR)5 ligand flagellin induces strong protective innate defense against
      microbial pathogens and hypothesized that flagellin modulates gene expression at
      the transcriptional levels. Thus, we sought to determine the role of one
      transcription factor, interferon regulatory factor (IRF1), and its target gene
      CXCL10 therein. METHODS: Superarray was used to identify transcription factors
      differentially expressed in Pseudomonas aeruginosa-challenged human corneal
      epithelial cells (CECs) with or without flagellin pretreatment. The expression of
      CXCL10, IRF1, LI-8(CXCL2), and IFNgamma was determined by PCR,
      immunohistochemistry, Western/dot blotting, and/or ELISA. IRF1 knockout mice,
      CXCL10 and IFNgamma neutralization, and NK cell depletion were used to define in
      vivo regulation and function of CXCL10. The severity of P. aeruginosa was
      assessed using clinical scoring, slit-lamp microscopy, bacterial counting,
      polymorphonuclear leukocytes (PMN) infiltration, and macrophage inflammatory
      protein 2/Chemokine (C-X-C motif) ligand 2 (MIP-2/CXCL2) expression. RESULTS:
      Flagellin pretreatment drastically affected P. aeruginosa-induced IRF1 expression
      in human CECs. However, flagellin pretreatment augmented the P. aeruginosa
      induced expression of Irf1 and its target gene Cxcl10 in B6 mouse corneas. Irf1
      deficiency reduced infection-triggered CXCL10 expression, increased keratitis
      severity, and attenuated flagellin-elicited protection compared to values in wild
      type (WT) controls. CXCL10 neutralization in the cornea of WT mice displayed
      pathogenesis similar to that of IRF1-/- mice. IFNgamma receptor neutralization
      and NK cell depletion prevented flagellin-augmented IRF1 and CXCL10 expression
      and increased the susceptibility to P. aeruginosa infection in mouse corneas.
      CONCLUSIONS: IRF1 plays a role in the corneal innate immune response by
      regulating CXCL10 expression. IFNgamma-producing NK cells augment the epithelial
      expression of IRF1 and CXCL10 and thus contribute to the innate defense of the
      cornea against P. aeruginosa infection.

PMID- 24130182
TI  - Shape of the posterior vitreous chamber in human emmetropia and myopia.
AB  - PURPOSE: To compare posterior vitreous chamber shape in myopia to that in
      emmetropia. METHODS: Both eyes of 55 adult subjects were studied, 27 with
      emmetropia (mean spherical error [MSE] >= -0.55; <+0.75 D; mean +0.09 +/- 0.36 D)
      and 28 with myopia (MSE -5.87 +/- 2.31 D). Cycloplegic refraction was measured
      with a Shin Nippon autorefractor and anterior chamber depth and axial length with
      a Zeiss IOLMaster. Posterior vitreous chamber shapes were determined from T2
      weighted magnetic resonance imaging (3.0-T) using procedures previously reported
      by our laboratory. Three-dimensional surface model coordinates were assigned to
      nasal, temporal, superior, and inferior quadrants and plotted in two dimensions
      to illustrate the composite shape of respective quadrants posterior to the second
      nodal point. Spherical analogues of chamber shape were constructed to compare
      relative sphericity between refractive groups and quadrants. RESULTS: Differences
      in shape occurred in the region posterior to points of maximum globe width and
      were thus in general accord with an equatorial model of myopic expansion. Shape
      in emmetropia is categorized distinctly as that of an oblate ellipse and in
      myopia as an oblate ellipse of significantly less degree such that it
      approximates to a sphere. There was concordance between shape and retinotopic
      projection of respective quadrants into right, left, superior, and inferior
      visual fields. CONCLUSIONS: Prolate ellipse posterior chamber shapes were rarely
      found in myopia, and we propose that spherical shape in myopia may constitute a
      biomechanical limitation on further axial elongation. Synchronization of quadrant
      shapes with retinotopic projection suggests that binocular growth is coordinated
      by processes that operate beyond the optic chiasm.

PMID- 24130184
TI  - The role of cGMP in ocular growth and the development of form-deprivation myopia
      in guinea pigs.
AB  - PURPOSE: Development of myopia is associated with remodeling of the sclera, a
      tissue composed principally of collagen. Cyclic guanosine monophosphate (cGMP)
      regulates collagen synthesis in several organs; therefore, we investigated the
      effects of soluble guanylyl cyclase (sGC) stimulation and inhibition on
      refraction and ocular growth in guinea pigs under normal and form-deprived (FD)
      conditions. METHODS: Retinal and scleral cGMP concentrations were measured in
      normal and monocularly FD guinea pigs at 2 days, 1 week, and 2 weeks of form
      deprivation and following 2 days recovery. Stimulation of sGC by BAY41-2272 and
      inhibition by NS-2028 were achieved by daily subconjunctival injection in normal
      and FD eyes. Refraction and axial parameters were measured at the commencement,
      middle, and cessation of the experiment. cGMP levels were also determined at the
      end of the experiment. RESULTS: Retinal and scleral cGMP concentrations increased
      in FD eyes from 2 days to 2 weeks (P <= 0.029). Levels decreased after 2 days of
      recovery (P <= 0.003). Daily injections of BAY41-2272 induced a myopic shift (P
      <= 0.001) and ocular elongation (P <= 0.01) in normal animals, but did not alter
      myopia in FD eyes (P > 0.05). In contrast, daily injections of NS-2028 partially
      reduced myopic shifts (P <= 0.012) and ocular elongation (P <= 0.015) induced by
      form deprivation, but did not affect ocular growth and refraction in normal eyes
      (P > 0.05). Retinal and scleral cGMP levels were increased by BAY41-2272 in
      normal eyes and decreased by NS-2028 in FD eyes. CONCLUSIONS: Changes in cGMP
      signaling contribute to myopic development. Thus, cGMP may be a potential
      therapeutic target for preventing/treating myopia.

PMID- 24130183
TI  - Amacrine cell subtypes differ in their intrinsic neurite growth capacity.
AB  - PURPOSE: Amacrine cell neurite patterning has been extensively studied in vivo,
      and more than 30 subpopulations with varied morphologies have been identified in
      the mammalian retina. It is not known, however, whether the complex amacrine cell
      morphology is determined intrinsically, is signaled by extrinsic cues, or both.
      METHODS: Here we purified rat amacrine cell subpopulations away from their
      retinal neighbors and glial-derived factors to ask questions about their
      intrinsic neurite growth ability. In defined medium strongly trophic for amacrine
      cells in vitro, we characterized survival and neurite growth of amacrine cell
      subpopulations defined by expression of specific markers. RESULTS: We found that
      a series of amacrine cell subtype markers are developmentally regulated, turning
      on through early postnatal development. Subtype marker expression was observed in
      similar fractions of cultured amacrine cells as was observed in vivo, and was
      maintained with time in culture. Overall, amacrine cell neurite growth followed
      principles very similar to those in postnatal retinal ganglion cells, but
      embryonic retinal ganglion cells demonstrated different features, relating to
      their rapid axon growth. Surprisingly, the three subpopulations of amacrine cells
      studied in vitro recapitulated quantitatively and qualitatively the varied
      morphologies they have in vivo. CONCLUSIONS: Our data suggest that cultured
      amacrine cells maintain intrinsic fidelity to their identified in vivo subtypes,
      and furthermore, that cell-autonomous, intrinsic factors contribute to the
      regulation of neurite patterning.

PMID- 24130185
TI  - Correlation between biomechanical responses of posterior sclera and IOP
      elevations during micro intraocular volume change.
AB  - PURPOSE: This study tested the hypothesis that intraocular pressure (IOP)
      elevations, induced by controlled increase of intraocular volume, are correlated
      with the biomechanical responses of the posterior sclera. METHODS: Porcine globes
      were tested within 48 hours postmortem. The first group of globes (n = 11) was
      infused with 15 MUL of phosphate-buffered saline at three different rates to
      investigate rate-dependent IOP elevations. The second group (n = 16) was first
      infused at the fast rate and then underwent inflation tests to investigate the
      relationship between IOP elevations (DeltaIOP) and scleral strains. The strains
      in the superotemporal region of the posterior sclera were measured by ultrasound
      speckle tracking. Linear regression was used to examine the association between
      DeltaIOP due to micro-volumetric infusion and the scleral strains at a specific
      inflation pressure. RESULTS: The average DeltaIOP was 14.9 +/- 4.3 mm Hg for the
      infusion of 15 MUL in 1 second. The DeltaIOP was greater for the faster infusion
      rates but highly correlated across different rates (P < 0.001). A significant
      negative association was found between the DeltaIOP and the tangential strains in
      both the circumferential (R(2) = 0.54, P = 0.003) and meridian (R(2) = 0.53, P =
      0.002) directions in the posterior sclera. CONCLUSIONS: This study showed a
      substantial increase in IOP, with a large intersubject variance during micro
      volumetric change. A stiffer response of the sclera was associated with larger
      IOP spikes, providing experimental evidence linking corneoscleral biomechanics to
      IOP fluctuation. In vivo measurement of corneoscleral biomechanics may help
      better predict the dynamic profile of IOP.

PMID- 24130186
TI  - Identification of epitopes within integrin beta4 for binding of auto-antibodies
      in ocular cicatricial and mucous membrane pemphigoid: preliminary report.
AB  - PURPOSE: To identify the epitopes on human beta4 integrin to which the sera of
      patients with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid
      (MMP) without ocular involvement bind. METHODS: Fragments of the intracellular
      domain of the beta4 molecule were cloned, expressed, purified and peptides were
      synthesized. Antibodies to various fragments and peptides were produced in
      rabbits. Binding specificity was determined via Western blot and blocking
      experiments. Test sera and controls were injected into neonatal BALB/c mice for
      in vivo passive transfer. RESULTS: Sera from patients with OCP, MMP, and both OCP
      and MMP were bound to cloned fragments of IC3.0. Its subcloned fragments IC3.4
      (1489 aa-1572 aa) and IC3.4.1 (1489 aa-1510 aa) were bound with the sera from
      patients with OCP only. Subcloned fragments IC3.6 (1573 aa-1822 aa) and IC3.6.1
      (1689 aa-1702 aa) were bound with MMP sera only. No cross-reactivity in binding
      was observed. Immuno-affinity-purified sera from patients with OCP, MMP, and
      rabbit antibodies to IC3.0, IC3.4, IC3.4.1, IC3.6, and IC3.6.1, when injected in
      neonatal BALB/c mice, produced subepidermal blisters in their skin. CONCLUSIONS:
      These preliminary observations identified IC3.4.1 as the possible epitope for the
      binding of OCP auto-antibody and IC3.6.1 as the possible epitope for the binding
      of MMP auto-antibody without ocular disease. Antibodies specific to these
      peptides produced blisters when injected in mice. Still-unidentified epitopes may
      exist. These observations may enhance our understanding of the role of beta4
      integrin in the pathobiology of OCP and MMP. Early diagnosis may be possible if
      serologic tests with specificity and sensitivity can be developed.

PMID- 24130187
TI  - Comparative study of macular ganglion cell-inner plexiform layer and
      peripapillary retinal nerve fiber layer measurement: structure-function analysis.
AB  - PURPOSE: We explored and compared the relationships between the visual field (VF)
      sensitivities assessed by standard automated perimetry (SAP), and the ganglion
      cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer
      (pRNFL) thicknesses as measured by Cirrus high-definition optical coherence
      tomography (HD-OCT) in glaucomatous eyes. METHODS: We enrolled 213 eyes of 213
      patients with glaucoma. The thicknesses of the average/sectoral GCIPL and pRNFL
      were measured by Cirrus HD-OCT. The mean sensitivity (MS) of 24-2 SAP was
      recorded on decibel and 1/L scales. The topographic relationships between
      structure and function were investigated. RESULTS: Statistically significant
      correlations between the corresponding VF sensitivity and the macular GCIPL
      thickness were found in all GCIPL sectors. Among six GCIPL sectors, the strongest
      association was observed between superonasal center MS and inferotemporal GCIPL
      thickness. In comparative analysis, the association between the central cluster
      MS and average GCIPL thickness was significantly stronger than that of temporal
      pRNFL thickness using the decibel scale (P < 0.001). The association between
      regional VF sensitivities, and the inferior hemifield and inferior GCIPL
      thicknesses were significantly stronger than those of the corresponding pRNFL
      thickness using the decibel scale (P = 0.001 and 0.007). CONCLUSIONS: The average
      and sectoral GCIPL thicknesses determined by Cirrus HD-OCT were associated
      significantly with global and regional VF sensitivity in patients with glaucoma.
      The macular GCIPL thickness values may provide more valuable information than
      temporal pRNFL thickness values for understanding the structure-function
      relationships of the macular region.

PMID- 24130188
TI  - Mechanically induced multicolor switching based on a single organic molecule.
AB  - Asserting its independence: A single organic molecule containing pyrene and
      rhodamine B chromophores separated by a peptide spacer formed a mechanochromic
      material whose fluorescence could be switched from blue to bluish-green and
      reddish by grinding. Modulation of the overlapped packing pattern of the pyrene
      excimer for blue emission was crucial for the reversible tricolored switching
      observed. 

PMID- 24130189
TI  - Multifunctional regulation of angiogenesis by high-density lipoproteins.
AB  - AIMS: High-density lipoproteins (HDL) exert striking anti-inflammatory effects
      and emerging evidence suggests that they may augment ischaemia-mediated
      neovascularization. We sought to determine whether HDL conditionally regulates
      angiogenesis, depending on the pathophysiological context by (i) inhibiting
      inflammation-induced angiogenesis, but also; (ii) enhancing ischaemia-mediated
      angiogenesis. METHODS AND RESULTS: Intravenously delivered apolipoprotein (apo) A
      I attenuated neovascularization in the murine femoral collar model of
      inflammation-induced angiogenesis, compared with phosphate-buffered saline
      infused C57BL6/J mice (58%), P < 0.05. Conversely, apoA-I delivery augmented
      neovessel formation (75%) and enhanced blood perfusion (45%) in the murine
      hindlimb ischaemia model, P < 0.05. Reconstituted HDL (rHDL) was tested on key
      angiogenic cell functions in vitro. rHDL inhibited human coronary artery
      endothelial cell migration (37.9 and 76.9%), proliferation (15.7 and 40.4%), and
      tubulogenesis on matrigel (52 and 98.7%) when exposed to two inflammatory
      stimuli: tumour necrosis factor-alpha (TNF-alpha) and macrophage-conditioned
      media (MCM). In contrast, rHDL significantly augmented hypoxia-stimulated
      migration (36.9%), proliferation (135%), and tubulogenesis (22.9%), P < 0.05.
      Western blot and RT-PCR analyses revealed that these divergent actions of rHDL
      were associated with conditional regulation of hypoxia-inducible factor-1alpha
      (HIF-1alpha), vascular endothelial growth factor (VEGF) and VEGF receptor 2,
      which were attenuated in response to TNF-alpha (40.4, 41.0, and 33.2%) and MCM
      (72.5, 30.7, and 69.5%), but augmented by rHDL in hypoxia (39.8, 152.6, and
      15.7%%), all P < 0.05. CONCLUSION: HDL differentially regulates angiogenesis
      dependent upon the pathophysiological setting, characterized by suppression of
      inflammation-associated angiogenesis, and conversely, by the enhancement of
      hypoxia-mediated angiogenesis. This has significant implications for therapeutic
      modulation of neovascularization.

PMID- 24130190
TI  - Melusin protects from cardiac rupture and improves functional remodelling after
      myocardial infarction.
AB  - AIMS: Melusin is a muscle-specific chaperone protein whose expression is required
      for a compensatory hypertrophy response to pressure overload. Here, we evaluated
      the consequences of melusin overexpression in the setting of myocardial
      infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:
      Mice overexpressing melusin in the heart (TG) and wild-type controls (WT) were
      subjected to permanent LAD ligation and both the acute response (Day 3) and
      subsequent remodelling (2 weeks) were examined. Mortality in wild-type mice was
      significant between Days 3 and 7, primarily due to cardiac rupture, but melusin's
      overexpression strongly reduced mortality (43.2% in wild-type vs. 27.3% in
      melusin-TG, P = 0.005). At Day 3 after MI, a time point preceding the mortality
      peak, TG hearts had increased heat shock protein 70 expression, increased ERK1/2
      signalling, reduced cardiomyocyte hyper-contractility and inflammatory cell
      infiltrates, and increased matricellular protein expression in the infarcted
      area. At 2 weeks after MI, melusin overexpression conferred a favourable adaptive
      remodelling characterized by reduced left ventricle dilatation and better
      preserved contractility in the presence of a comparable degree of hypertrophy.
      Adaptive remodelling in melusin TG mice was characterized by reduced apoptosis
      and fibrosis as well as increased cardiomyocyte contractility. CONCLUSIONS:
      Consistent with its function as a chaperone protein, melusin overexpression
      exerts a dual protective action following MI reducing an array of maladaptive
      processes. In the early phase after MI, reduced inflammation and myocyte
      remodelling protect against cardiac rupture. Chronically, reduced myocyte loss
      and matrix remodelling, with preserved myocyte contractility, confer adaptive LV
      remodelling.

PMID- 24130191
TI  - para-Substituted 2-phenyl-3,4-dihydroquinazolin-4-ones as potent and selective
      tankyrase inhibitors.
AB  - Human tankyrases are attractive drug targets, especially for the treatment of
      cancer. We identified a set of highly potent tankyrase inhibitors based on a 2
      phenyl-3,4-dihydroquinazolin-4-one scaffold. Substitutions at the para position
      of the scaffold's phenyl group were evaluated as a strategy to increase potency
      and improve selectivity. The best compounds displayed single-digit nanomolar
      potencies, and profiling against several human diphtheria-toxin-like ADP
      ribosyltransferases revealed that a subset of these compounds are highly
      selective tankyrase inhibitors. The compounds also effectively inhibit Wnt
      signaling in HEK293 cells. The binding mode of all inhibitors was studied by
      protein X-ray crystallography. This allowed us to establish a structural basis
      for the development of highly potent and selective tankyrase inhibitors based on
      the 2-phenyl-3,4-dihydroquinazolin-4-one scaffold and outline a rational approach
      to the modification of other inhibitor scaffolds that bind to the nicotinamide
      site of the catalytic domain. 

PMID- 24130192
TI  - A remarkable self-organization process as the origin of primitive functional
      cells.

PMID- 24130193
TI  - The conserved chimeric transcript UPGRADE2 is associated with unreduced pollen
      formation and is exclusively found in apomictic Boechera species.
AB  - In apomictic Boechera spp., meiotic diplospory leads to the circumvention of
      meiosis and the suppression of recombination to produce unreduced male and female
      gametes (i.e. apomeiosis). Here, we have established an early flower
      developmental staging system and have performed microarray-based comparative gene
      expression analyses of the pollen mother cell stage in seven diploid sexual and
      seven diploid apomictic genotypes to identify candidate factors for unreduced
      pollen formation. We identified a transcript unique to apomictic Boechera spp.
      called UPGRADE2 (BspUPG2), which is highly up-regulated in their pollen mother
      cells. BspUPG2 is highly conserved among apomictic Boechera spp. genotypes but
      has no homolog in sexual Boechera spp. or in any other taxa. BspUPG2 undergoes
      posttranscriptional processing but lacks a prominent open reading frame. Together
      with the potential of stably forming microRNA-like secondary structures, we
      hypothesize that BspUPG2 functions as a long regulatory noncoding messenger RNA
      like RNA. BspUPG2 has apparently arisen through a three-step process initiated by
      ancestral gene duplication of the original BspUPG1 locus, followed by sequential
      insertions of segmentally duplicated gene fragments, with final exonization of
      its sequence structure. Its genesis reflects the hybridization history that
      characterizes the genus Boechera. 

PMID- 24130194
TI  - Proteome analysis of peroxisomes from etiolated Arabidopsis seedlings identifies
      a peroxisomal protease involved in beta-oxidation and development.
AB  - Plant peroxisomes are highly dynamic organelles that mediate a suite of metabolic
      processes crucial to development. Peroxisomes in seeds/dark-grown seedlings and
      in photosynthetic tissues constitute two major subtypes of plant peroxisomes,
      which had been postulated to contain distinct primary biochemical properties.
      Multiple in-depth proteomic analyses had been performed on leaf peroxisomes, yet
      the major makeup of peroxisomes in seeds or dark-grown seedlings remained
      unclear. To compare the metabolic pathways of the two dominant plant peroxisomal
      subtypes and discover new peroxisomal proteins that function specifically during
      seed germination, we performed proteomic analysis of peroxisomes from etiolated
      Arabidopsis (Arabidopsis thaliana) seedlings. The detection of 77 peroxisomal
      proteins allowed us to perform comparative analysis with the peroxisomal proteome
      of green leaves, which revealed a large overlap between these two primary
      peroxisomal variants. Subcellular targeting analysis by fluorescence microscopy
      validated around 10 new peroxisomal proteins in Arabidopsis. Mutant analysis
      suggested the role of the cysteine protease RESPONSE TO DROUGHT21A-LIKE1 in beta
      oxidation, seed germination, and growth. This work provides a much-needed road
      map of a major type of plant peroxisome and has established a basis for future
      investigations of peroxisomal proteolytic processes to understand their roles in
      development and in plant interaction with the environment. 

PMID- 24130195
TI  - Deciphering the responses of root border-like cells of Arabidopsis and flax to
      pathogen-derived elicitors.
AB  - Plant pathogens including fungi and bacteria cause many of the most serious crop
      diseases. The plant innate immune response is triggered upon recognition of
      microbe-associated molecular patterns (MAMPs) such as flagellin22 and
      peptidoglycan. To date, very little is known of MAMP-mediated responses in roots.
      Root border cells are cells that originate from root caps and are released
      individually into the rhizosphere. Root tips of Arabidopsis (Arabidopsis
      thaliana) and flax (Linum usitatissimum) release cells known as "border-like
      cells." Whereas root border cells of pea (Pisum sativum) are clearly involved in
      defense against fungal pathogens, the function of border-like cells remains to be
      established. In this study, we have investigated the responses of root border
      like cells of Arabidopsis and flax to flagellin22 and peptidoglycan. We found
      that both MAMPs triggered a rapid oxidative burst in root border-like cells of
      both species. The production of reactive oxygen species was accompanied by
      modifications in the cell wall distribution of extensin epitopes. Extensins are
      hydroxyproline-rich glycoproteins that can be cross linked by hydrogen peroxide
      to enhance the mechanical strength of the cell wall. In addition, both MAMPs also
      caused deposition of callose, a well-known marker of MAMP-elicited defense.
      Furthermore, flagellin22 induced the overexpression of genes involved in the
      plant immune response in root border-like cells of Arabidopsis. Our findings
      demonstrate that root border-like cells of flax and Arabidopsis are able to
      perceive an elicitation and activate defense responses. We also show that cell
      wall extensin is involved in the innate immunity response of root border-like
      cells. 

PMID- 24130196
TI  - A two-hybrid-receptor assay demonstrates heteromer formation as switch-on for
      plant immune receptors.
AB  - Receptor kinases sense extracellular signals and trigger intracellular signaling
      and physiological responses. However, how does signal binding to the
      extracellular domain activate the cytoplasmic kinase domain? Activation of the
      plant immunoreceptor Flagellin sensing2 (FLS2) by its bacterial ligand flagellin
      or the peptide-epitope flg22 coincides with rapid complex formation with a second
      receptor kinase termed brassinosteroid receptor1 associated kinase1 (BAK1). Here,
      we show that the receptor pair of FLS2 and BAK1 is also functional when the roles
      of the complex partners are reversed by swapping their cytosolic domains. This
      reciprocal constellation prevents interference by redundant partners that can
      partially substitute for BAK1 and demonstrates that formation of the heteromeric
      complex is the molecular switch for transmembrane signaling. A similar approach
      with swaps between the Elongation factor-Tu receptor and BAK1 also resulted in a
      functional receptor/coreceptor pair, suggesting that a "two-hybrid-receptor
      assay" is of more general use for studying heteromeric receptor complexes. 

PMID- 24130197
TI  - Rice WRKY13 regulates cross talk between abiotic and biotic stress signaling
      pathways by selective binding to different cis-elements.
AB  - Plants use a complex signal transduction network to regulate their adaptation to
      the ever-changing environment. Rice (Oryza sativa) WRKY13 plays a vital role in
      the cross talk between abiotic and biotic stress signaling pathways by
      suppressing abiotic stress resistance and activating disease resistance. However,
      it is not clear how WRKY13 directly regulates this cross talk. Here, we show that
      WRKY13 is a transcriptional repressor. During the rice responses to drought
      stress and bacterial infection, WRKY13 selectively bound to certain site- and
      sequence-specific cis-elements on the promoters of SNAC1 (for STRESS RESPONSIVE
      NO APICAL MERISTEM, ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR1/2, CUP-SHAPED
      COTYLEDON), the overexpression of which increases drought resistance, and WRKY45
      1, the knockout of which increases both bacterial disease and drought resistance.
      WRKY13 also bound to two cis-elements of its native promoter to autoregulate the
      balance of its gene expression in different physiological activities. WRKY13 was
      induced in leaf vascular tissue, where bacteria proliferate, during infection,
      and in guard cells, where the transcriptional factor SNAC1 enhances drought
      resistance, during both bacterial infection and drought stress. These results
      suggest that WRKY13 regulates the antagonistic cross talk between drought and
      disease resistance pathways by directly suppressing SNAC1 and WRKY45-1 and
      autoregulating its own expression via site- and sequence-specific cis-elements on
      the promoters of these genes in vascular tissue where bacteria proliferate and
      guard cells where the transcriptional factor SNAC1 mediates drought resistance by
      promoting stomatal closure. 

PMID- 24130198
TI  - A template-based approach to inhibitors of calpain 2, 20S proteasome, and HIV-1
      protease.
AB  - Specificity counts: A template-based approach to protease inhibitors is presented
      using a core macrocycle that presents a generic beta-strand template for binding
      to protease active sites. This is then specifically functionalized at P2 , and
      the C and N termini to give inhibitors of calpain 2, 20S proteasome, and HIV-1
      protease. 

PMID- 24130199
TI  - Proceedings of the University of Pennsylvania 5th annual conference on
      statistical issues in clinical trials: emerging statistical issues in biomarker
      validation for clinical trials.

PMID- 24130200
TI  - University of Pennsylvania 5th annual conference on statistical issues in
      clinical trials: emerging statistical issues in biomarker validation (Morning
      Session).

PMID- 24130201
TI  - Inference from blinded data in randomized clinical trials.
AB  - BACKGROUND: With blinded data, several authors have concluded that there is a
      negligible chance of inferring a non-null treatment effect. The recent Food and
      Drug Administration (FDA) draft guidance document on adaptive trials, by
      encouraging blinded sample size reestimation, implies the same. PURPOSE: We
      derive methods to investigate whether the probability of inferring a treatment
      effect is much larger than previously thought, and whether that is of concern.
      METHODS: A statistic is developed that contributes to improving signal detection.
      Additionally, trials that are overpowered, for reasons external to powering the
      primary objective, further strengthen the chance of finding a signal. RESULTS: An
      example of data from a clinical trial shows how revealing a blinded analysis can
      be. The ability to infer a non-null effect while a blinded trial is ongoing is a
      serious matter. LIMITATIONS: The methods apply to superiority trials and are of
      limited use for non-inferiority or equivalence trials. CONCLUSION: It is
      important, therefore, that guidance documents include clear language to limit or
      prevent inference from blinded data to maintain trial integrity. Simple steps are
      proposed to make inference difficult.

PMID- 24130202
TI  - Application of methods for central statistical monitoring in clinical trials.
AB  - BACKGROUND: On-site source data verification is a common and expensive activity,
      with little evidence that it is worthwhile. Central statistical monitoring (CSM)
      is a cheaper alternative, where data checks are performed by the coordinating
      centre, avoiding the need to visit all sites. Several publications have suggested
      methods for CSM; however, few have described their use in real trials. METHODS: R
      programs were created to check data at either the subject level (7 tests within 3
      programs) or site level (9 tests within 8 programs) using previously described
      methods or new ones we developed. These aimed to find possible data errors such
      as outliers, incorrect dates, or anomalous data patterns; digit preference,
      values too close or too far from the means, unusual correlation structures,
      extreme variances which may indicate fraud or procedural errors and under
      reporting of adverse events. The methods were applied to three trials, one of
      which had closed and has been published, one in follow-up, and a third to which
      fabricated data were added. We examined how well the methods work, discussing
      their strengths and limitations. RESULTS: The R-programs produced simple tables
      or easy-to-read figures. Few data errors were found in the first two trials, and
      those added to the third were easily detected. The programs were able to identify
      patients with outliers based on single or multiple variables. They also detected
      (1) fabricated patients, generated to have values too close to the multivariate
      mean, or with too low variances in repeated measurements, and (2) sites which had
      unusual correlation structures or too few adverse events. Some methods were
      unreliable if applied to centres with few patients or if data were fabricated in
      a way which did not fit the assumptions used to create the programs. Outputs from
      the R-programs are interpreted using examples. LIMITATIONS: Detecting data errors
      is relatively straightforward; however, there are several limitations in the
      detection of fraud: some programs cannot be applied to small trials or to centres
      with few patients (<10) and data falsified in a manner which does not fit the
      program's assumptions may not be detected. In addition, many tests require a
      visual assessment of the output (showing flagged participants or sites), before
      data queries are made or on-site visits performed. CONCLUSIONS: CSM is a
      worthwhile alternative to on-site data checking and may be used to limit the
      number of site visits by targeting only sites which are picked up by the
      programs. We summarise the methods, show how they are implemented and that they
      can be easy to interpret. The methods can identify incorrect or unusual data for
      a trial subject, or centres where the data considered together are too different
      to other centres and therefore should be reviewed, possibly through an on-site
      visit.

PMID- 24130203
TI  - Hypoglycaemic haemiparesis.
AB  - Hypoglycaemic haemiparesis (HH) is an uncommon but important presentation to the
      emergency department, and it often mimics stroke and is therefore frequently
      misdiagnosed by clinicians. The mechanism of haemiparesis is not fully
      understood. This case outlines a diabetic elderly woman, who had been having
      frequent hypoglycaemic episodes and presented to paramedics with hypoglycaemia
      associated with a right-sided haemiparesis. She was immediately transferred to
      the local stroke centre after presenting to the emergency department. CT and MRI
      did not fit in with her presenting neurology. Her weakness resolved, after
      normoglycaemia was achieved with dextrose infusion; however, she was reported to
      be more sleepy and drowsy than usual. After extensive and costly investigations
      during her prolonged inpatient stay, her unifying diagnosis was an HH which
      triggered of a hypoactive delirium. 

PMID- 24130204
TI  - Primary presentation of chronic calcific pancreatitis with massive unilateral
      pleural effusion.
AB  - We described a 45-year-old previously healthy man presenting with progressively
      worsening breathlessness for 10 days. Physical examination was suggestive of a
      left-sided pleural effusion. A chest X-ray was confirmatory. Analysis of
      aspirated fluid showed a lymphocytic exudate with grossly elevated amylase and
      lipase levels. CT revealed chronic calcific pancreatitis as the underlying cause
      of effusion. Retrospective questioning failed to identify classical symptoms of
      chronic pancreatitis including abdominal pain and steatorrhoea. The patient was
      managed with intercostal drainage and supportive care. Although unusual, chronic
      pancreatitis should be kept as a differential diagnosis in patients with
      unilateral exudative pleural effusion. Elevated fluid levels of amylase and
      lipase are useful clues to this uncommon diagnosis. 

PMID- 24130205
TI  - Neonatal Currarino's syndrome presenting as intestinal obstruction.

PMID- 24130206
TI  - Transient bradycardia induced by thiopentone sodium: a unique challenge in the
      management of refractory status epilepticus.
AB  - Thiopentone sodium is one of the important drugs in the armamentarium for
      terminating refractory status epilepticus, a neurological emergency. We report a
      case of thiopentone-related bradycardia during the management of the new onset
      refractory status epilepticus in a young man, which was circumvented by
      prophylactic insertion of temporary pacemaker while thiopentone infusion was
      continued. A systematic approach was employed to manage the status epilepticus,
      including infusion of thiamine and glucose followed by antiepileptic drugs. The
      patient was ventilated and infused with lorazepam, phenytoin, sodium valproate,
      levetiracetam and midazolam followed by thiopentone sodium. With the introduction
      of thiopentone the seizures could be controlled but the patient developed severe
      bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone
      was withdrawn and reappeared when the drug was reintroduced. Propofol infusion
      was tried with no respite in seizures. Later thiopentone sodium was reintroduced
      after inserting temporary cardiac pacemaker. Seizure was controlled and patient
      was weaned off the ventilator. 

PMID- 24130207
TI  - Management of haemangioma with sclerosing agent: a case report.
AB  - The use of multiple weekly intralesional injections of 3% sodium tetradecyl
      sulfate as a sclerosing agent for the management of facial haemangiomas is a safe
      treatment with acceptable results. As presented in this case report, this
      technique offers the patient considerable relief of symptoms with minimal
      complications. However, the possibility of second-stage surgery to correct
      residual deformity is still considered. Sclerotherapy with 3% sodium tetradecyl
      sulfate provides a good preparation for further surgery. 

PMID- 24130208
TI  - Hypertriglyceridaemic pancreatitis.

PMID- 24130209
TI  - Infected transverse colonic cystic duplication simulating pelvic appendicular
      abscess.

PMID- 24130210
TI  - Multifocal necrotising fasciitis and septic shock complicating varicella
      infection in an adult.
AB  - A 35-year-old woman with a 3-day history of chickenpox, presented to the hospital
      in septic shock and with multifocal, non-adjacent lesions of necrotising
      fasciitis. Necrotising fasciitis is a rare yet life-threatening complication of
      chickenpox. Blood cultures and wound swabs confirmed the presence of
      Streptococcus pyogenes. The initial emergency management included oxygen,
      aggressive fluid resuscitation and antimicrobial therapy. Once the patient was
      stabilised, surgical management ensued. This included debridement and eventual
      grafting of the necrotic skin lesions. Intensive management and follow-up for 8
      weeks were required before the patient was deemed fit for discharge. 

PMID- 24130211
TI  - Changes in phosphatidylinositol 3-kinase 55 kDa gamma expression and subcellular
      localization may be caspase 6 dependent in paraquat-induced SH-SY5Y apoptosis.
AB  - The neurotoxin paraquat (PQ) causes apoptosis of dopaminergic neurons in
      mammalian cell culture and animal models, mimicking an important pathological
      feature of Parkinson's disease (PD). The phosphoinositide 3-kinase (PI3K)/Akt
      pathway is critical for several major survival signals in central nervous system
      neurons. Phosphatidylinositol 3-kinase 55 kDa gamma (p55PIK) is a regulatory
      subunit of PI3Ks with important roles in cell proliferation, antiapoptosis, and
      cell cycle progression. However, p55PIK involvement in mechanisms regarding
      progression and maintenance of neurodegenerative diseases is largely
      undetermined. We used PQ-induced apoptosis in human dopaminergic SH-SY5Y cells to
      investigate the association between p55PIK expression levels, subcellular
      location, and apoptosis. p55PIK expression was reduced in SH-SY5Y cells and
      p55PIK messenger RNA and protein expression levels were decreased after PQ
      treatment. Apoptosis induced by PQ was associated with caspase activation and
      decreased p55PIK expression. Restoration of p55PIK expression was observed after
      coincubation with a caspase inhibitor. Overexpressed full-length p55PIK in SH
      SY5Y and human embryonic kidney 293 cells showed specific distribution in the
      nucleus and was cleaved in vitro by recombinant caspase 6 (C6), but not C3 and
      C7. A p55PIK construct lacking 24 N-terminal amino acids (N24) was tested for the
      presence of a potential C6-recognizable sequence and was found to express its
      proteins outside the nucleus. The results suggest that p55PIK may be involved in
      PQ-induced apoptosis signal transduction and that N24 is crucial for p55PIK
      subcellular localization. Thus, p55PIK could be a substrate of activated C6
      during apoptosis, leading to loss of original biological functions and
      redistribution to disturb cell cycle progression. 

PMID- 24130212
TI  - Dynamics of oxidative/nitrosative stress in mice with methionine-choline
      deficient diet-induced nonalcoholic fatty liver disease.
AB  - Insulin resistance, oxidative stress, and proinflammatory cytokines play a key
      role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our
      study was to investigate the dynamics of oxidative/nitrosative stress in
      methionine-choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice
      were divided into following groups: group 1: control group on standard diet;
      group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively).
      After treatment, liver and blood samples were taken for histopathology, alanine-
      and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative
      stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups
      versus control group (p < 0.01), while nitrites + nitrates level showed a
      progressive increase. The activity of total superoxide dismutase and its
      isoenzymes was significantly lower in all MCD-fed groups (p < 0.01). Although
      catalase activity was significantly lower in MCD-fed animals at all intervals (p
      < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver
      content of glutathione was lower in MCD4 (p < 0.05) and MCD6 group (p < 0.01)
      versus control. : Ferritin and C-reactive protein serum concentration were
      significantly higher only in MCD6 group. Our study suggests that MCD diet induces
      a progressive rise in nitrosative stress in the liver. Additionally, the most
      prominent decrease in liver antioxidative capacity is in the fourth week, which
      implies that application of antioxidants would be most suitable in this period,
      in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.

PMID- 24130213
TI  - In vivo comet assay of a novel galacto-oligosaccharide in rats.
AB  - A novel galacto-oligosaccharide (GOS) manufactured by a two-step enzyme reaction
      of lactose was examined in a comet assay for its potential to induce DNA damage
      in vivo by estimating the DNA fragmentation level in the cellular nuclei of the
      glandular stomach, colon, and peripheral blood. GOS was orally administered at
      doses of 0 (vehicle alone), 500, 1000, and 2000 mg/kg/day to five male Crl:
      CD(Sprague Dawley) rats per group three times (48, 24, and 3 h before the animals
      were terminated). The specimens were prepared in accordance with the standard
      protocol (version 14.2) of the "International Validation of the In Vivo Rodent
      Alkaline Comet Assay for the Detection of Genotoxic Carcinogens" organized by the
      Japanese Center for the Validation of Alternative Methods. No significant
      differences in the percentage of DNA in the tail were observed between the GOS
      treated groups and vehicle controls in any of the organs evaluated. Additionally,
      no GOS-related clinical signs or effects on body weight were seen. Based on these
      results, the comet assay of GOS in the glandular stomach, colon, and peripheral
      blood using rats was judged negative. Therefore, it is concluded that GOS did not
      induce DNA damage in vivo under the conditions employed in this study. 

PMID- 24130214
TI  - Octanal-induced inflammatory responses in cells relevant for lung toxicity:
      expression and release of cytokines in A549 human alveolar cells.
AB  - Inhalation is an important route of aldehyde exposure, and lung is one of the
      main targets of aldehyde toxicity. Octanal is distributed ubiquitously in the
      environment and is a component of indoor air pollutants. We investigated whether
      octanal exposure enhances the inflammatory response in the human respiratory
      system by increasing the expression and release of cytokines and chemokines. The
      effect of octanal in transcriptomic modulation was assessed in the human alveolar
      epithelial cell line A549 using oligonucleotide arrays. We identified a set of
      genes differentially expressed upon octanal exposure that may be useful for
      monitoring octanal pulmonary toxicity. These genes were classified according to
      the Gene Ontology functional category and Kyoto Encyclopedia of Genes and Genomes
      analysis to explore the biological processes related to octanal-induced pulmonary
      toxicity. The results show that octanal affects the expression of several
      chemokines and inflammatory cytokines and increases the levels of interleukin 6
      (IL-6) and IL-8 released. In conclusion, octanal exposure modulates the
      expression of cytokines and chemokines important in the development of lung
      injury and disease. This suggests that inflammation contributes to octanal
      induced lung damage and that the inflammatory genes expressed should be studied
      in detail, thereby laying the groundwork for future biomonitoring studies. 

PMID- 24130215
TI  - Di(2-ethylhexyl)phthalate exposure impairs insulin receptor and glucose
      transporter 4 gene expression in L6 myotubes.
AB  - Di(2-ethyl hexyl)-phthalate (DEHP) is an endocrine disrupter and is the most
      abundantly used phthalate derivative, which is suspected to be an inevitable
      environmental exposure contributing to the increasing incidence of type-2
      diabetes in humans. Therefore, the present study was designed to address the dose
      dependent effects of DEHP on insulin signaling molecules in L6 myotubes. L6
      myotubes were exposed to different concentrations (25, 50, and 100 MUM) of DEHP
      for 24 h. At the end of exposure, cells were utilized for assessing various
      parameters. Insulin receptor and glucose transporter4 (GLUT4) gene expression,
      insulin receptor protein concentration, glucose uptake and oxidation, and
      enzymatic and nonenzymatic antioxidants were significantly reduced, but glutamine
      fructose-6-phosphate amidotransferase, nitric oxide, lipid peroxidation, and
      reactive oxygen species levels were elevated in a dose-dependent manner in L6
      myotubes exposed to DEHP. The present study in turn shows the direct adverse
      effect of DEHP on the expression of insulin receptor and GLUT4 gene, glucose
      uptake, and oxidation in L6 myotubes suggesting that DEHP exposure may have a
      negative influence on insulin signaling. 

PMID- 24130216
TI  - Genipin as a sporicidal agent for the treatment of cortical bone allografts.
AB  - INTRODUCTION: Microbial bioburden in bone allografts can be reduced by gamma
      radiation; however, the radiation compromises collagen and increases the risk of
      graft failure. Genipin is an agent that may reduce bioburden by chemical
      crosslinking without causing mechanical detriment or cytotoxicity. METHODS: To
      evaluate genipin's ability to penetrate cortical bone while maintaining
      sporicidal activity, Bacillus subtilis spore strips were isolated between slices
      of bovine femoral cortical bone and immersed in genipin solutions for up to one
      week; spore viability was assessed with media-based assays. The mechanical
      effects of genipin treatment were assessed by performing three-point bending
      tests on genipin-treated cortical beams. Cytotoxicity studies were conducted by
      evaluating the adhesion and proliferation of murine MC3T3-E1 (P21) preosteoblasts
      on cortical bone slices which were treated with genipin and rinsed to different
      extents. RESULTS: Genipin successfully penetrated cortical bone slices and
      sterilized B. subtilis populations after 48 hours (p>0.05) and one week (p<0.05).
      Genipin-treated cortical beams demonstrated dose-dependent increases in yield
      strain (p=0.02) and resilience (p<0.01), whereas other mechanical properties were
      not affected by genipin treatment. Seeding cells onto inadequately rinsed genipin
      treated bones proved cytotoxic. However, with adequate post-treatment rinsing of
      the residual genipin, cell adhesion and proliferation was comparable to phosphate
      buffered saline-treated controls (no genipin). CONCLUSIONS: Genipin solutions can
      sterilize bacterial spore populations entrapped within the continuum of bone
      tissue while preserving mechanical properties of bone and allowing cell adhesion
      and proliferation. Provided that antimicrobial effects seen with bacterial spores
      extend broadly to all microbial and viral species, genipin holds strong potential
      for bone allograft sterilization.

PMID- 24130218
TI  - Announcing the AACR Cancer Progress Report 2013.

PMID- 24130219
TI  - Comparison of biodegradable and titanium fixation systems in maxillofacial
      surgery: a two-year multi-center randomized controlled trial.
AB  - Biodegradable osteosynthesis could reduce/delete the problems associated with
      titanium plate removal. The aim of the present study was to compare the clinical
      performance in the first 2 post-operative years between a biodegradable and a
      titanium system in oral and maxillofacial surgery. The multicenter randomized
      controlled trial (RCT) was performed in the Netherlands from December 2006 to
      July 2009. Included were 230 patients who underwent a bilateral sagittal split
      osteotomy (BSSO) and/or a Le Fort-I osteotomy and those treated for fractures of
      the mandible, maxilla, or zygoma. The patients were randomly assigned to a
      titanium group (KLS Martin) or to a biodegradable group (Inion CPS). Plate
      removal was necessary in 16 of the 134 patients (11.9%) treated with titanium and
      in 21 of the 87 patients (24.1%) treated with the biodegradable system within the
      first 2 post-operative years [p = .016, HR biodegradable (95% CI) = 2.2 (1.1
      4.2), HR titanium = 1]. Occlusion, VAS, and MFIQ scores showed that both groups
      had good mandibular function and were (almost) free of pain 1 and 2 years post
      operatively (http://controlled-trials.com ISRCTN 44212338). 

PMID- 24130220
TI  - Nitric oxide signaling contributes to ectopic orofacial neuropathic pain.
AB  - Inferior alveolar nerve (IAN) injury induces persistent ectopic pain which
      spreads to a wide area in the orofacial region. Its exact mechanism remains
      unclear. We investigated the involvement of nitric oxide (NO) in relation to
      ectopic orofacial pain caused by IAN transection (IANX). We assessed the changes
      in mechanical sensitivity of the whisker pad skin following IANX, neuronal nitric
      oxide synthase (nNOS) expression in the trigeminal ganglion (TG), and the
      functional significance of NO in relation to the mechanical allodynia following
      intra-TG administration of a chemical precursor to NO and selective nNOS
      inhibitors. IANX induced mechanical allodynia, which was diminished by intra-TG
      administration of selective nNOS inhibitors. NO metabolites and nNOS
      immunoreactive neurons innervating the lower lip were also increased in the TG.
      Intra-TG administration of nNOS substrate induced the mechanical allodynia. The
      present findings suggest that NO released from TG neurons regulates the
      excitability of TG neurons innervating the whisker pad skin, and the enhancement
      of TG neuronal excitability may underlie ectopic mechanical allodynia. 

PMID- 24130221
TI  - Explaining variance in the cumulus mammographic measures that predict breast
      cancer risk: a twins and sisters study.
AB  - BACKGROUND: Mammographic density, the area of the mammographic image that appears
      white or bright, predicts breast cancer risk. We estimated the proportions of
      variance explained by questionnaire-measured breast cancer risk factors and by
      unmeasured residual familial factors. METHODS: For 544 MZ and 339 DZ twin pairs
      and 1,558 non-twin sisters from 1,564 families, mammographic density was measured
      using the computer-assisted method Cumulus. We estimated associations using
      multilevel mixed-effects linear regression and studied familial aspects using a
      multivariate normal model. RESULTS: The proportions of variance explained by age,
      body mass index (BMI), and other risk factors, respectively, were 4%, 1%, and 4%
      for dense area; 7%, 14%, and 4% for percent dense area; and 7%, 40%, and 1% for
      nondense area. Associations with dense area and percent dense area were in
      opposite directions than for nondense area. After adjusting for measured factors,
      the correlations of dense area with percent dense area and nondense area were
      0.84 and -0.46, respectively. The MZ, DZ, and sister pair correlations were 0.59,
      0.28, and 0.29 for dense area; 0.57, 0.30, and 0.28 for percent dense area; and
      0.56, 0.27, and 0.28 for nondense area (SE = 0.02, 0.04, and 0.03, respectively).
      CONCLUSIONS: Under the classic twin model, 50% to 60% (SE = 5%) of the variance
      of mammographic density measures that predict breast cancer risk are due to
      undiscovered genetic factors, and the remainder to as yet unknown individual
      specific, nongenetic factors. IMPACT: Much remains to be learnt about the genetic
      and environmental determinants of mammographic density.

PMID- 24130222
TI  - Oxidative stress, dietary antioxidant supplements, and health: is the glass half
      full or half empty?

PMID- 24130223
TI  - Characterizing the temporal dynamics of human papillomavirus DNA detectability
      using short-interval sampling.
AB  - BACKGROUND: Variable detection of human papillomavirus (HPV) DNA can result in
      misclassification of infection status, but the extent of misclassification has
      not been quantitatively evaluated. METHODS: In 2005-2007, 33 women of ages 22 to
      53 years self-collected vaginal swabs twice per week for 16 consecutive weeks.
      Each of the 955 swabs collected was tested for 37 HPV types/subtypes. Assuming
      that a woman's underlying infection status did not change over the short study
      period, biases in prevalence estimates obtained from single versus multiple swabs
      were calculated. Using event history analysis methods, time to recurrent gain and
      loss of at least one HPV type was determined, separately. Baseline any-type and
      high risk-type HPV prevalence was 60.6% and 24.2%, respectively. Cumulative any
      HPV and high-risk HPV prevalence over the 16-week period was 84.8% and 60.6%,
      separately. RESULTS: Overall, there were 319 events of detection and 313 events
      of loss of detection. Median times to a recurrent detection and loss of detection
      were 11 and seven days, respectively. Neither vaginal sex nor condom use during
      follow-up was associated with recurrent viral detection or loss of detection.
      Assuming the cumulative 16-week prevalence reflects the true prevalence of
      infection, the baseline any-HPV prevalence underestimated infection status by
      24.2%, with a bootstrapped mean of 20.2% [95% confidence interval (CI), 8.9%
      29.6%]. CONCLUSIONS: These findings suggest that a substantial proportion of HPV
      infected women are misclassified as being uninfected when using a single-time DNA
      measurement. IMPACT: Short-term variation in detectable HPV DNA needs to be
      considered while interpreting the natural history of infections using single
      samples collected at long intervals.

PMID- 24130224
TI  - Prostate-specific membrane antigen protein expression in tumor tissue and risk of
      lethal prostate cancer.
AB  - BACKGROUND: Overexpression of prostate-specific membrane antigen (PSMA) in tumor
      tissue and serum has been linked to increased risk of biochemical recurrence in
      surgically treated prostate cancer patients, but none of the studies have
      assessed its association with disease-specific mortality. METHODS: We examined
      whether high PSMA protein expression in prostate tumor tissue was associated with
      lethal disease, and with tumor biomarkers of progression, among participants of
      two U.S.-based cohorts (n = 902, diagnosed 1983-2004). We used Cox proportional
      hazards regression to calculate multivariable HRs and 95% confidence intervals
      (CI) of lethal prostate cancer, defined as disease-specific death or development
      of distant metastases (n = 95). Partial Spearman rank correlation coefficients
      were used to correlate PSMA with tumor biomarkers. RESULTS: During an average 13
      years of follow-up, higher PSMA expression at prostatectomy was significantly
      associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1 = 2.42;
      Ptrend < 0.01). This association was attenuated and nonsignificant (multivariable
      adjusted HRQ4vs.Q1 = 1.01; Ptrend = 0.52) after further adjusting for Gleason
      score and prostate-specific antigen (PSA) at diagnosis. High PSMA expression was
      significantly (P < 0.05) correlated with higher Gleason score and PSA at
      diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen
      receptor expression, and absence of ets-related gene (ERG) expression.
      CONCLUSIONS: High tumor PSMA expression was not an independent predictor of
      lethal prostate cancer in the current study. PSMA expression likely captures, in
      part, malignant features of Gleason grade and tumor angiogenesis. IMPACT: PSMA is
      not a strong candidate biomarker for predicting prostate cancer-specific
      mortality in surgically treated patients.

PMID- 24130225
TI  - Tanning bed use is not associated with internal cancer risk: evidence from a
      large cohort study.
AB  - BACKGROUND: Increased risk of skin cancer by indoor tanning has drawn public
      attention. However, there are arguments that tanning bed use increases vitamin D
      production, which may therefore prevent internal cancers. METHODS: We followed
      73,358 female nurses for 20 years (1989-2009) in the Nurses' Health Study II and
      investigated the frequency of tanning bed use during high school/college and at
      ages 25 to 35 in relation to the incidence of total cancers (excluding skin
      cancers). We used multivariate Cox proportional hazards models to estimate the
      HRs and 95% confidence intervals (CI) of total cancers and each individual major
      cancer with more than 100 cases. RESULTS: During follow-up, a total of 4,271
      internal cancer-related cases were diagnosed. No association was found between
      tanning bed use and risk of total cancers (multivariable-adjusted HR, 0.99; 95%
      CI, 0.95-1.04 for every 4 times/y use on average during high school/college and
      at ages 25-35). In addition, no association was found for the risk of any
      individual major cancers, such as breast cancer, thyroid cancer, colorectal
      cancer, non-Hodgkin lymphoma, or endometrial cancer. CONCLUSIONS: Our data do not
      suggest any association between the use of tanning beds and risk of internal
      cancers. IMPACT: On the basis of the strong evidence of increase in skin cancer
      risk and no evidence of reduction in internal cancer risk by tanning bed use, it
      is important to warn the public against indoor tanning.

PMID- 24130226
TI  - Mate drinking and esophageal squamous cell carcinoma in South America: pooled
      results from two large multicenter case-control studies.
AB  - BACKGROUND: Mate tea is a nonalcoholic infusion widely consumed in southern South
      America, and may increase risk of esophageal squamous cell carcinoma (ESCC) and
      other cancers due to polycyclic aromatic hydrocarbons (PAH) and/or thermal
      injury. METHODS: We pooled two case-control studies: a 1988 to 2005 Uruguay study
      and a 1986 to 1992 multinational study in Argentina, Brazil, Paraguay, and
      Uruguay, including 1,400 cases and 3,229 controls. We computed ORs and fitted a
      linear excess OR (EOR) model for cumulative mate consumption in liters/day-year
      (LPDY). RESULTS: The adjusted OR for ESCC with 95% confidence interval (CI) by
      ever compared with never use of mate was 1.60 (1.2-2.2). ORs increased linearly
      with LPDY (test of nonlinearity; P = 0.69). The estimate of slope (EOR/LPDY) was
      0.009 (0.005-0.014) and did not vary with daily intake, indicating mate intensity
      did not influence the strength of association. EOR/LPDY estimates for consumption
      at warm, hot, and very hot beverage temperatures were 0.004 (-0.002-0.013), 0.007
      (0.003-0.013), and 0.016 (0.009-0.027), respectively, and differed significantly
      (P < 0.01). EOR/LPDY estimates were increased in younger (<65) individuals and
      never alcohol drinkers, but these evaluations were post hoc, and were homogeneous
      by sex. CONCLUSIONS: ORs for ESCC increased linearly with cumulative mate
      consumption and were unrelated to intensity, so greater daily consumption for
      shorter duration or lesser daily consumption for longer duration resulted in
      comparable ORs. The strength of association increased with higher mate
      temperatures. IMPACT: Increased understanding of cancer risks with mate
      consumption enhances the understanding of the public health consequences given
      its purported health benefits.

PMID- 24130227
TI  - Microbial aetiology of healthcare associated pneumonia in Spain: a prospective,
      multicentre, case-control study.
AB  - INTRODUCTION: Healthcare-associated pneumonia (HCAP) is actually considered a
      subgroup of hospital-acquired pneumonia due to the reported high risk of
      multidrug-resistant pathogens in the USA. Therefore, current American Thoracic
      Society/Infectious Diseases Society of America guidelines suggest a nosocomial
      antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting
      this is contradictory. METHODS: We conducted a prospective multicentre case
      control study in Spain, comparing clinical presentation, outcomes and microbial
      aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age
      (+/-10 years), gender and period of admission (+/-10 weeks). RESULTS: 476
      patients (238 cases, 238 controls) were recruited for 2 years from June 2008.
      HCAP cases showed significantly more comorbidities (including dysphagia), higher
      frequency of previous antibiotic use in the preceding month, higher pneumonia
      severity score and worse clinical status (Charslon and Barthel scores). While
      microbial aetiology did not differ between the two groups (HCAP and CAP:
      Streptococcus pneumoniae: 51% vs 55%; viruses: 22% vs 12%; Legionella: 4% vs 9%;
      Gram-negative bacilli: 5% vs 4%; Pseudomonas aeruginosa: 4% vs 1%), HCAP patients
      showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP,
      9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs
      1.5%) and readmission rate (18% vs 11%) (p<0.05, each). CONCLUSIONS: Despite a
      similar clinical presentation, HCAP was more severe due to patients' conditions
      (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP
      did not differ from CAP indicating that it is not related to increased mortality
      and in Spain most HCAP patients do not need nosocomial antibiotic coverage.

PMID- 24130228
TI  - Inhaled corticosteroids in COPD and the risk of serious pneumonia.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are known to increase the risk of
      pneumonia in patients with chronic obstructive pulmonary disease (COPD). It is
      unclear whether the risk of pneumonia varies for different inhaled agents,
      particularly fluticasone and budesonide, and increases with the dose and long
      term duration of use. METHODS: We formed a new-user cohort of patients with COPD
      treated during 1990-2005. Subjects were identified using the Quebec health
      insurance databases and followed through 2007 or until a serious pneumonia event,
      defined as a first hospitalisation for or death from pneumonia. A nested case
      control analysis was used to estimate the rate ratio (RR) of serious pneumonia
      associated with current ICS use, adjusted for age, sex, respiratory disease
      severity and comorbidity. RESULTS: The cohort included 163 514 patients, of which
      20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence
      rate 2.4/100/year). Current use of ICS was associated with a 69% increase in the
      rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75). The risk was sustained
      with long-term use and declined gradually after stopping ICS use, disappearing
      after 6 months (RR 1.08; 95% CI 0.99 to 1.17). The rate of serious pneumonia was
      higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily
      dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).
      CONCLUSIONS: ICS use by patients with COPD increases the risk of serious
      pneumonia. The risk is particularly elevated and dose related with fluticasone.
      While residual confounding cannot be ruled out, the results are consistent with
      those from recent randomised trials.

PMID- 24130231
TI  - Developing and evaluating an automated appendicitis risk stratification algorithm
      for pediatric patients in the emergency department.
AB  - OBJECTIVE: To evaluate a proposed natural language processing (NLP) and machine
      learning based automated method to risk stratify abdominal pain patients by
      analyzing the content of the electronic health record (EHR). METHODS: We analyzed
      the EHRs of a random sample of 2100 pediatric emergency department (ED) patients
      with abdominal pain, including all with a final diagnosis of appendicitis. We
      developed an automated system to extract relevant elements from ED physician
      notes and lab values and to automatically assign a risk category for acute
      appendicitis (high, equivocal, or low), based on the Pediatric Appendicitis
      Score. We evaluated the performance of the system against a manually created gold
      standard (chart reviews by ED physicians) for recall, specificity, and precision.
      RESULTS: The system achieved an average F-measure of 0.867 (0.869 recall and
      0.863 precision) for risk classification, which was comparable to physician
      experts. Recall/precision were 0.897/0.952 in the low-risk category, 0.855/0.886
      in the high-risk category, and 0.854/0.766 in the equivocal-risk category. The
      information that the system required as input to achieve high F-measure was
      available within the first 4 h of the ED visit. CONCLUSIONS: Automated
      appendicitis risk categorization based on EHR content, including information from
      clinical notes, shows comparable performance to physician chart reviewers as
      measured by their inter-annotator agreement and represents a promising new
      approach for computerized decision support to promote application of evidence
      based medicine at the point of care.

PMID- 24130229
TI  - Risk factors for community-acquired pneumonia in adults in Europe: a literature
      review.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) causes considerable morbidity and
      mortality in adults, particularly in the elderly. METHODS: Structured searches of
      PubMed were conducted to identify up-to-date information on the incidence of CAP
      in adults in Europe, as well as data on lifestyle and medical risk factors for
      CAP. RESULTS: The overall annual incidence of CAP in adults ranged between 1.07
      to 1.2 per 1000 person-years and 1.54 to 1.7 per 1000 population and increased
      with age (14 per 1000 person-years in adults aged >=65 years). Incidence was also
      higher in men than in women and in patients with chronic respiratory disease or
      HIV infection. Lifestyle factors associated with an increased risk of CAP
      included smoking, alcohol abuse, being underweight, having regular contact with
      children and poor dental hygiene. The presence of comorbid conditions, including
      chronic respiratory and cardiovascular diseases, cerebrovascular disease,
      Parkinson's disease, epilepsy, dementia, dysphagia, HIV or chronic renal or liver
      disease all increased the risk of CAP by twofold to fourfold. CONCLUSION: A range
      of lifestyle factors and underlying medical conditions are associated with an
      increased risk of CAP in European adults. Understanding of the types of
      individual at greatest risk of CAP can help to ensure that interventions to
      reduce the risk of infection and burden of disease are targeted appropriately.

PMID- 24130232
TI  - Barriers and facilitators to implementing electronic prescription: a systematic
      review of user groups' perceptions.
AB  - OBJECTIVE: We conducted a systematic review identifying users groups' perceptions
      of barriers and facilitators to implementing electronic prescription (e
      prescribing) in primary care. METHODS: We included studies following these
      criteria: presence of an empirical design, focus on the users' experience of e
      prescribing implementation, conducted in primary care, and providing data on
      barriers and facilitators to e-prescribing implementation. We used the Donabedian
      logical model of healthcare quality (adapted by Barber et al) to analyze our
      findings. RESULTS: We found 34 publications (related to 28 individual studies)
      eligible to be included in this review. These studies identified a total of 594
      elements as barriers or facilitators to e-prescribing implementation. Most user
      groups perceived that e-prescribing was facilitated by design and technical
      concerns, interoperability, content appropriate for the users, attitude towards e
      prescribing, productivity, and available resources. DISCUSSION: This review
      highlights the importance of technical and organizational support for the
      successful implementation of e-prescribing systems. It also shows that the same
      factor can be seen as a barrier or a facilitator depending on the project's own
      circumstances. Moreover, a factor can change in nature, from a barrier to a
      facilitator and vice versa, in the process of e-prescribing implementation.
      CONCLUSIONS: This review summarizes current knowledge on factors related to e
      prescribing implementation in primary care that could support decision makers in
      their design of effective implementation strategies. Finally, future studies
      should emphasize on the perceptions of other user groups, such as pharmacists,
      managers, vendors, and patients, who remain neglected in the literature.

PMID- 24130234
TI  - CIHR to simplify open-funding programs.

PMID- 24130233
TI  - MIRD pamphlet No. 24: Guidelines for quantitative 131I SPECT in dosimetry
      applications.
AB  - The reliability of radiation dose estimates in internal radionuclide therapy is
      directly related to the accuracy of activity estimates obtained at each imaging
      time point. The recently published MIRD pamphlet no. 23 provided a general
      overview of quantitative SPECT imaging for dosimetry. The present document is the
      first in a series of isotope-specific guidelines that will follow MIRD 23 and
      focuses on one of the most commonly used therapeutic radionuclides, (131)I. The
      purpose of this document is to provide guidance on the development of protocols
      for quantitative (131)I SPECT in radionuclide therapy applications that require
      regional (normal organs, lesions) and 3-dimensional dosimetry. 

PMID- 24130235
TI  - Lack of leadership responsible for rising HIV infection levels in some provinces:
      HIV expert.

PMID- 24130236
TI  - Lichen amyloidosis.

PMID- 24130238
TI  - Health minister ends special access to prescription heroin.

PMID- 24130239
TI  - Syrian refugees desperately need our help.

PMID- 24130240
TI  - Police call for more mental health services.

PMID- 24130242
TI  - Iron supplementation for children: Safety in all settings is not clear.

PMID- 24130243
TI  - Effects of daily iron supplementation in primary-school-aged children: systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Anemia is an important public health and clinical problem.
      Observational studies have linked iron deficiency and anemia in children with
      many poor outcomes, including impaired cognitive development; however, iron
      supplementation, a widely used preventive and therapeutic strategy, is associated
      with adverse effects. Primary-school-aged children are at a critical stage in
      intellectual development, and optimization of their cognitive performance could
      have long-lasting individual and population benefits. In this study, we summarize
      the evidence for the benefits and safety of daily iron supplementation in primary
      school-aged children. METHODS: We searched electronic databases (including
      MEDLINE and Embase) and other sources (July 2013) for randomized and quasi
      randomized controlled trials involving daily iron supplementation in children
      aged 5-12 years. We combined the data using random effects meta-analysis.
      RESULTS: We identified 16 501 studies; of these, we evaluated 76 full-text papers
      and included 32 studies including 7089 children. Of the included studies, 31 were
      conducted in low- or middle-income settings. Iron supplementation improved global
      cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI]
      0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean
      difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and
      concentration. Iron supplementation also improved age-adjusted height among all
      children and age-adjusted weight among anemic children. Iron supplementation
      reduced the risk of anemia by 50% and the risk of iron deficiency by 79%.
      Adherence in the trial settings was generally high. Safety data were limited.
      INTERPRETATION: Our analysis suggests that iron supplementation safely improves
      hematologic and nonhematologic outcomes among primary-school-aged children in low
      or middle-income settings and is well-tolerated.

PMID- 24130245
TI  - E-cigarettes "modestly effective" tool to quit smoking.

PMID- 24130244
TI  - Crystal methamphetamine and initiation of injection drug use among street
      involved youth in a Canadian setting.
AB  - BACKGROUND: Although injection drug use is known to result in a range of health
      related harms, including transmission of HIV and fatal overdose, little is known
      about the possible role of synthetic drugs in injection initiation. We sought to
      determine the effect of crystal methamphetamine use on risk of injection
      initiation among street-involved youth in a Canadian setting. METHODS: We used
      Cox regression analyses to identify predictors of injection initiation among
      injection-naive street-involved youth enrolled in the At-Risk Youth Study, a
      prospective cohort study of street-involved youth in Vancouver, British Columbia.
      Data on circumstances of first injection were also obtained. RESULTS: Between
      October 2005 and November 2010, a total of 395 drug injection-naive, street
      involved youth provided 1434 observations, with 64 (16.2%) participants
      initiating injection drug use during the follow-up period, for a cumulative
      incidence of 21.7 (95% confidence interval [CI] 1.7-41.7) per 100 person-years.
      In multivariable analysis, recent noninjection use of crystal methamphetamine was
      positively associated with subsequent injection initiation (adjusted hazard ratio
      1.93, 95% CI 1.31-2.85). The drug of first injection was most commonly reported
      as crystal methamphetamine (14/31 [45%]). INTERPRETATION: Noninjection use of
      crystal methamphetamine predicted subsequent injection initiation, and crystal
      methamphetamine was the most commonly used drug at the time of first injection.
      Evidence-based strategies to prevent transition to injection drug use among
      crystal methamphetamine users are urgently needed.

PMID- 24130246
TI  - Doctor freed from Egyptian jail no extremist: colleagues.

PMID- 24130247
TI  - Transtibial versus independent drilling techniques for anterior cruciate ligament
      reconstruction: a systematic review, meta-analysis, and meta-regression.
AB  - BACKGROUND: While numerous cadaveric, in vivo, and clinical studies have compared
      transtibial and independent drilling of femoral tunnels during anterior cruciate
      ligament reconstruction, there is no evidence-based consensus on which technique
      affords the best outcome. HYPOTHESIS: There is no difference in clinical outcome
      between transtibial and independent drilling of femoral tunnels. STUDY DESIGN:
      Systematic review with meta-analysis and meta-regression. METHODS: Cadaveric, in
      vivo, and clinical studies comparing transtibial and independent drilling
      techniques were systematically identified. A qualitative synthesis of
      nonrandomized studies and meta-analysis of randomized controlled trials (RCTs)
      were performed. In addition, a meta-regression analysis of RCTs that did not
      directly compare drilling techniques was performed. RESULTS: A total of 49
      studies were included in the qualitative review, and 15 were included in the meta
      analysis; 22 studies were included in the meta-regression. In biomechanical
      studies, independent drilling placed the center of the femoral tunnel closer to
      the center of the femoral footprint (mean difference, 2.69 mm; 95% CI, 0.46-4.92;
      P < .00001). Independent drilling reduced anterior tibial translation with the
      Lachman examination (mean difference, 2.2 mm; 95% CI, 0.34-4.07; P = .02), 134 N
      of anterior load (mean difference, 1 mm; 95% CI, 0.29-1.71; P = .006), and
      simulated pivot shift (mean difference, 3.36 mm; 95% CI, 1.88-4.85; P < .00001).
      The meta-analysis showed improved Lysholm scores with independent drilling (mean
      difference, -0.62 points; 95% CI, -1.09 to -0.55; P = .009), although the
      clinical relevance of this small difference is questionable. There were no
      significant differences in International Knee Documentation Committee (IKDC)
      objective scores or Tegner scores between groups. With the meta-regression, there
      were no significant differences in failure rates or IKDC objective scores.
      CONCLUSION: While there are biomechanical data suggesting improved knee stability
      and more anatomic graft placement with independent drilling, no significant
      clinical differences were found between the 2 techniques. CLINICAL RELEVANCE: The
      current evidence shows that transtibial and independent drilling techniques have
      equivalent clinical outcomes at short-term to midterm follow-up. The long-term
      effects of subtle differences in tunnel position and postoperative knee
      kinematics should be further studied in dedicated, prospective cohort and
      randomized studies.

PMID- 24130248
TI  - Innovations in materials for direct restorations: why do we need innovations? Why
      is it so hard to capitalize on them?

PMID- 24130249
TI  - Mineral association changes the secondary structure and dynamics of murine
      amelogenin.
AB  - Amelogenin is one of the key protein constituents responsible for the exquisite
      organization of the calcium phosphate crystals in enamel. Amelogenin forms into
      nanospheres in solution, while its association with hydroxyapatite is also
      essential to enamel development. Structural information of full-length amelogenin
      in either of these physiologically important forms has the potential to provide
      mechanistic information; however, these data are limited because of the
      difficulty of determining the structure of large protein complexes and proteins
      bound to surfaces. To obtain structural insights into amelogenin during these
      early stages of enamel development, we used a lysine-specific (13)C-, (15)N
      labeled sample of murine amelogenin to provide insight into the structure of the
      hydroxyapatite (HAP)-binding domains of the protein. A combination of one-and two
      dimensional solid-state NMR experiments was used to obtain molecular-level
      insights into the secondary structure and dynamics of full-length amelogenin
      within a nanosphere-gel and on the surface of HAP. Regions of amelogenin that
      appear to be primarily random coil in the nanosphere-gel adopt a beta-strand
      structure and are less mobile with HAP binding, indicative of a structural switch
      upon binding that may be important in the role of amelogenin in enamel
      development. 

PMID- 24130250
TI  - Hypercalcemia in the Intensive Care Unit: A Review of Pathophysiology, Diagnosis,
      and Modern Therapy.
AB  - Hypercalcemia may be seen in a variety of clinical settings and often requires
      intensive management when serum calcium levels are dramatically elevated. All of
      the many etiologies of mild hypercalcemia can lead to severe hypercalcemia.
      Knowledge of the physiologic mechanisms involved in maintaining normocalcemia and
      basic pathophysiology is essential for making a timely diagnosis and hence prompt
      institution of etiology-specific therapy. The development of new medications and
      critical reviews of traditional therapies have changed the treatment paradigm for
      severe hypercalcemia, calling for a more limited role for aggressive isotonic
      fluid administration and furosemide and an expanded role for calcitonin and the
      bisphosphonates. Experimental therapies such as denosumab show promise. 

PMID- 24130251
TI  - Perceptions of participation in a phase I, II, or III clinical trial among
      African American patients with cancer: what do refusers say?
AB  - BACKGROUND: Less than 5% of all adult patients with cancer enter clinical trials.
      These rates are lower in racial/ethnic minority populations, negatively affecting
      the generalizability and validity of trial results. Many studies have identified
      barriers to minority enrolment, yet few have gathered in-depth insights into
      minority patients' reasons for trial refusal. We aimed to (1) explore trial
      refusal reasons in a sample of African American (AA) patients with cancer who
      declined trial participation and (2) gather patients' perceptions of the
      potential benefit of an array of decision support tools. METHODS: Participants
      were 22 consecutively recruited AA patients with cancer who had declined
      participation in a therapeutic clinical trial. Within 3 months of the trial
      refusal decision, participants completed an audio-recorded semistructured
      interview that asked about demographic and disease information, psychosocial
      factors, and patients' experience with clinical trials. Two months later,
      participants completed a questionnaire that asked about their trial decision.
      RESULTS: Few patients received positive recommendations about joining a trial.
      Patients gave multiple refusal reasons. Only two participants refused to join a
      clinical trial as a result of issues of mistrust. Most participants refused as a
      result of fears of additional burdens and adverse effects. Many patients and
      family members misunderstood trial information. Family members mostly recommended
      against trial participation. Most patients felt that question prompt lists or
      decision aids would assist information seeking and decision making. CONCLUSION:
      Low rates of physician recommendations for clinical trial participation of AA
      patients with cancer warrant further investigation. Interventions to reduce
      misunderstandings and aid decision making, both within and external to the
      clinical interaction, need to target both patients and family members.

PMID- 24130253
TI  - Shared vision, collective impact, and persistent challenges: the first decade of
      Georgia's oncology research network.
AB  - Ten years ago, Georgia was lauded for dedicating a portion of tobacco settlement
      funds to the Georgia Cancer Coalition (GCC). The plan championed by then-Governor
      Roy E. Barnes was designed to make Georgia a leader in prevention, treatment, and
      research. This plan called for the expansion of clinical trials to ensure
      Georgians had access to the highest quality care based on the most current
      treatments and discoveries. As a result, oncologists in the state were engaged in
      a planning process that resulted in a shared vision to improve the quality of
      cancer care through research and the formation of a new organization: the Georgia
      Center for Oncology Research and Education. 

PMID- 24130254
TI  - Overcoming recruitment challenges in palliative care clinical trials.
AB  - PURPOSE: Palliative care is increasingly viewed as a necessary component of
      cancer care, especially for patients with advanced disease. Rigorous clinical
      trials are thus needed to build the palliative care evidence base, but clinical
      research-especially participant recruitment-is difficult. Major barriers include
      (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss
      an approach to overcoming these barriers, using the Palliative Care Trial (PCT)
      as a case study. PATIENTS AND METHODS: The PCT was a 2 * 2 * 2 factorial
      randomized controlled trial (RCT) of different service delivery models to improve
      pain control in the palliative setting. It used a recruitment protocol that fused
      evidence-based strategies with principles of "social marketing," an approach
      involving the systematic application of marketing techniques. Main components
      included (1) an inclusive triage algorithm, (2) information booklets targeting
      particular stakeholders, (3) a specialized recruitment nurse, and (4)
      standardization of wording across all study communications. RESULTS: From an
      eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months.
      Twenty percent of patients referred to the palliative care service were enrolled
      (76% of those eligible after screening). Several common barriers were minimized;
      among those who declined participation, family disinterest was uncommon (5%), as
      was the perception of burden imposed (4%). CONCLUSION: Challenges to clinical
      trial recruitment in palliative care are significant but not insurmountable. A
      carefully crafted recruitment and retention protocol can be effective. Our
      experience with designing and deploying a social-marketing-based protocol shows
      the benefits of such an approach.

PMID- 24130252
TI  - The National Cancer Institute-American Society of Clinical Oncology Cancer Trial
      Accrual Symposium: summary and recommendations.
AB  - INTRODUCTION: Many challenges to clinical trial accrual exist, resulting in
      studies with inadequate enrollment and potentially delaying answers to important
      scientific and clinical questions. METHODS: The National Cancer Institute (NCI)
      and the American Society of Clinical Oncology (ASCO) cosponsored the Cancer Trial
      Accrual Symposium: Science and Solutions on April 29-30, 2010 to examine the
      state of accrual science related to patient/community, physician/provider, and
      site/organizational influences, and identify new interventions to facilitate
      clinical trial enrollment. The symposium featured breakout sessions, plenary
      sessions, and a poster session including 100 abstracts. Among the 358 attendees
      were clinical investigators, researchers of accrual strategies, research
      administrators, nurses, research coordinators, patient advocates, and educators.
      A bibliography of the accrual literature in these three major areas was provided
      to participants in advance of the meeting. After the symposium, the literature in
      these areas was revisited to determine if the symposium recommendations remained
      relevant within the context of the current literature. RESULTS: Few rigorously
      conducted studies have tested interventions to address challenges to clinical
      trials accrual. Attendees developed recommendations for improving accrual and
      identified priority areas for future accrual research at the patient/community,
      physician/provider, and site/organizational levels. Current literature continues
      to support the symposium recommendations. CONCLUSIONS: A combination of
      approaches addressing both the multifactorial nature of accrual challenges and
      the characteristics of the target population may be needed to improve accrual to
      cancer clinical trials. Recommendations for best practices and for future
      research developed from the symposium are provided.

PMID- 24130256
TI  - A biological motion toolbox for reading, displaying, and manipulating motion
      capture data in research settings.
AB  - Biological motion research is an increasingly active field, with a great
      potential to contribute to a wide range of applications, such as behavioral
      monitoring/motion detection in surveillance situations, intention inference in
      social interactions, and diagnostic tools in autism research. In recent years, a
      large amount of motion capture data has become freely available online,
      potentially providing rich stimulus sets for biological motion research. However,
      there currently does not exist an easy-to-use tool to extract, present and
      manipulate motion capture data in the MATLAB environment, which many researchers
      use to program their experiments. We have developed the Biomotion Toolbox, which
      allows researchers to import motion capture data in a variety of formats, to
      display actions using Psychtoolbox 3, and to manipulate action displays in
      specific ways (e.g., inversion, three-dimensional rotation, spatial scrambling,
      phase-scrambling, and limited lifetime). The toolbox was designed to allow
      researchers with a minimal level of MATLAB programming skills to code experiments
      using biological motion stimuli. 

PMID- 24130255
TI  - Coaching intervention as a strategy for minority recruitment to cancer clinical
      trials.
AB  - PURPOSE: Lack of trust and rapport with health care providers has been identified
      in the under-representation of racial/ethnic minorities within clinical trials.
      Our study used a coach to promote trust among minority patients with advanced
      cancer. PATIENTS AND METHODS: Minority patients with advanced breast, colorectal,
      lung, or prostate carcinoma were randomly assigned to receive a coach
      Intervention (CI) or usual care (UC). All patients completed baseline and 6-month
      telephone interviews to assess demographics, trust in health care providers,
      attitudes toward clinical trials, and quality of life. Patients randomly assigned
      to CI were assigned a coach, who made biweekly contacts for 6 months to address
      general issues, progress or development in cancer care, and available resources.
      Patients randomly assigned to UC received the standard of care, without this
      intervention. Clinical trial enrollment was assessed. RESULTS: Over 21 months, we
      screened 268 patients and enrolled 73 African Americans and two Asian Americans.
      Patients were randomly assigned to CI (n = 38) or to UC (n = 37). Longitudinal
      analyses were conducted on 69 patients who completed the 6-month follow-up
      assessment. Trial enrollment was 16 and 13 patients for the CI and UC groups,
      respectively. This difference was not significant (P = .351). Higher quality of
      life (1-point odds ratio on Functional Assessment of Cancer Treatment-General =
      1.033, P = .036) and positive attitudes toward trials predicted enrollment. There
      was no significant difference between these groups in quality of life, attitudes
      toward clinical trials, perceptions of racism, trust in doctors, or depression.
      CONCLUSIONS: Quality of life and positive attitude toward trials predicted trial
      enrollment, regardless of assignment to CI or UC.

PMID- 24130259
TI  - Depth perception from dynamic occlusion in motion parallax: roles of expansion
      compression versus accretion-deletion.
AB  - Motion parallax, or differential retinal image motion from observer movement,
      provides important information for depth perception. We previously measured the
      contribution of shear motion parallax to depth, which is only composed of
      relative motion information. Here, we examine the roles of relative motion and
      accretion-deletion information in dynamic occlusion motion parallax. Observers
      performed two-alternative forced choice depth-ordering tasks in response to low
      spatial frequency patterns of horizontal random dot motion that were synchronized
      to the observer's head movements. We examined conditions that isolated or
      combined expansion-compression and accretion-deletion across a range of simulated
      relative depths. At small depths, expansion-compression provided reliable depth
      perception while accretion-deletion had a minor contribution: When the two were
      in conflict, the perceived depth was dominated by expansion-compression. At
      larger depths in the cue-conflict experiment, accretion-deletion determined the
      depth-ordering performance. Accretion-deletion in isolation did not yield any
      percept of depth even though, in theory, it provided sufficient information for
      depth ordering. Thus, accretion-deletion can substantially enhance depth
      perception at larger depths but only in the presence of relative motion. The
      results indicate that expansion-compression contributes to depth from motion
      parallax across a broad range of depths whereas accretion-deletion contributes
      primarily at larger depths. 

PMID- 24130260
TI  - Protecting our science.
AB  - In response to a recent court decision, the Annals of Occupational Hygiene is
      reviewing our procedures to ensure transparency in authorship and direct and
      indirect conflicts of interest. These improvements are intended to help protect
      the integrity of the science presented in the journal. 

PMID- 24130261
TI  - Concerning statements made in "Determinants of exposure to 2-butoxyethanol from
      cleaning tasks: a quasi-experimental study" by Bello, A. et al., Ann. Occup.
      Hyg., Vol. 57, No. 1, pp. 125-135, 2013.

PMID- 24130262
TI  - Gross total but not incomplete resection of glioblastoma prolongs survival in the
      era of radiochemotherapy.
AB  - BACKGROUND: This prospective multicenter study assessed the prognostic influence
      of the extent of resection when compared with biopsy only in a contemporary
      patient population with newly diagnosed glioblastoma. PATIENTS AND METHODS:
      Histology, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation
      status, and clinical data were centrally analyzed. Survival analyses were carried
      out with the Kaplan-Meier method. Prognostic factors were assessed with
      proportional hazard models. RESULTS: Of 345 patients, 273 underwent open tumor
      resection and 72 biopsies; 125 patients had gross total resections (GTRs) and
      148, incomplete resections. Surgery-related morbidity was lower after biopsy
      (1.4% versus 12.1%, P = 0.007). 64.3% of patients received radiotherapy and
      chemotherapy (RT plus CT), 20.0% RT alone, 4.3% CT alone, and 11.3% best
      supportive care as an initial treatment. Patients <=60 years with a Karnofsky
      performance score (KPS) of >=90 were more likely to receive RT plus CT (P <
      0.01). Median overall survival (OS) (progression free survival; PFS) ranged from
      33.2 months (15 months) for patients with MGMT-methylated tumors after GTR and RT
      plus CT to 3.0 months (2.4 months) for biopsied patients receiving supportive
      care only. Favorable prognostic factors in multivariate analyses for OS were age
      <=60 years [hazard ratio (HR) = 0.52; P < 0.001], preoperative KPS of >=80 (HR =
      0.55; P < 0.001), GTR (HR = 0.60; P = 0.003), MGMT promoter methylation (HR =
      0.44; P < 0.001), and RT plus CT (HR = 0.18, P < 0.001); patients undergoing
      incomplete resection did not better than those receiving biopsy only (HR = 0.85;
      P = 0.31). CONCLUSIONS: The value of incomplete resection remains questionable.
      If GTR cannot be safely achieved, biopsy only might be used as an alternative
      surgical strategy.

PMID- 24130263
TI  - Prognostic factors for 60-day mortality in first-line treatment of metastatic
      colorectal cancer (mCRC): individual patient analysis of four randomised,
      controlled trials by the AIO colorectal cancer study group.
AB  - BACKGROUND: The 60 day mortality is an established parameter for chemotherapy
      related safety in randomised trials for metastatic colorectal cancer (mCRC).
      Prognostic factors associated with 60-day mortality would be helpful to identify
      high-risk patients in advance. PATIENTS AND METHODS: Individual baseline patient
      data from four randomised, controlled trials from the Arbeitsgemeinschaft
      Internistische Onkologie (AIO) study group were retrospectively analysed.
      Chemotherapy consisted of fluoropyrimidine (5-FU/capecitabine), irinotecan,
      oxaliplatin with or without bevacizumab or cetuximab. Prognostic factors were
      identified by univariate and multivariate logistic regression models in two
      cohorts: one limited to ECOG PS 0 and 1 and one including ECOG PS 2 patients.
      RESULTS: A total of 1377 patients were evaluated. The analysis of ECOG PS 0, 1
      and 2 patients consisted of 898 patients where a total of 33 deaths within the
      first 60 days of treatment (3.7%) occurred. In multivariate analysis, 60-day
      mortality was significantly associated with ECOG PS 2 and high leucocyte count
      (white blood cell, WBC). Odds ratio was 6.28 for WBC and 12.92 for ECOG PS 2.
      Exclusion of ECOG PS 2 patients but inclusion of one trial limited to ECOG PS 0
      and 1 patients resulted in 1302 assessable patients and 44 early deaths (3.4%).
      In both cohorts, around 50% of deaths were disease related. WBC was confirmed as
      a significant risk factor for early death (OR 7.60). A combined score using ECOG
      PS 2 and WBC >=8.000/ul is able to identify high-risk patients with a sensitivity
      of 18% and specificity of 98%. CONCLUSIONS: In this large retrospective analysis
      of individual patient data, around 50% of early deaths were disease related.
      Elevated WBC was found strongly associated with increased 60-day mortality in
      first-line treatment of mCRC. The proposed AIO-60-Day-Mortality score serves as
      an additional trial exclusion criterion.

PMID- 24130264
TI  - Prognostic role of early versus late onset of bone metastasis in patients with
      carcinoma of the ovary, peritoneum and fallopian tube.
AB  - BACKGROUND: Bone metastases are a rare manifestation in the management of ovarian
      cancer and thought to be associated with a poor prognosis as sign of distant
      spread. Only few data exist on this rare condition. The present study aimed to
      more information on this very distinct patient collective. PATIENTS AND METHODS:
      A retrospective chart review was carried out including all patients who had been
      treated from 1994 to 2009 for histologically confirmed ovarian, peritoneal and
      fallopian tube cancer. Overall, 1717 cases were detected and screened. Patients
      with bone metastasis were identified and analyzed regarding survival as well as
      various clinical variables. RESULTS: A total of 26 women who had been diagnosed
      with bone metastases ante mortem could be identified, resulting in an incidence
      of 1.50%. The majority of patients presented multiple bone lesions (80.8%) and
      bone spread was symptomatic in 62.5% of the cases. Mean overall survival from
      primary diagnosis of EOC was 50.5 months (range: 2.5-142.5 months). Median
      overall survival after diagnosis of bone metastases was 7.2 months. When divided
      into two subsets depending on timepoint diagnosis of bone metastases, there was a
      significant difference in overall survival. The mean overall survival from
      primary diagnosis of EOC in the early-onset group (n = 8), defined as occurence
      of bone manifestation within 12 months, was 11.2 months. The mean overall
      survival in the late-onset group (n = 15) was 78.4 months (P = 0.000001).
      CONCLUSIONS: The time interval from diagnosis to appearance of bone metastases is
      a prognostic factor in ovarian cancer. While early onset bone spread has a strong
      negative prognostic impact, late-onset bone diagnosis of bone metastases hardly
      influences the prognosis at all. This finding should be considered in the
      management of patients with bone metastases from ovarian cancer.

PMID- 24130265
TI  - Health status has improved more in women than in men with rheumatoid arthritis
      from 1994 to 2009: results from the Oslo rheumatoid arthritis register.
AB  - OBJECTIVE: To examine changes in patient reported outcome measures (PROs) over 15
      years in a representative population of patients with rheumatoid arthritis (RA),
      with a particular focus on gender differences. PATIENTS AND METHODS: Patients in
      the Oslo RA register filled in questionnaires including the Modified Health
      Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS)
      and mental component summaries and derived utility (SF-6D), visual analogue
      scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue,
      and checklists of medication commonly used in the treatment of RA. Data were
      collected at five time points during a 15-year period from 1994. Mixed model
      analyses were used to analyse longitudinal changes in PROs from 1994 to 1996,
      2001, 2004 and 2009. RESULTS: Data were available from 829-1025 RA patients at
      each time point. PROs were statistically significantly improved from 1994 to 2009
      (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p<0.001), and
      also with clinically important improvement. Men reported significantly better
      health status than women in 1994, but women improved significantly more than men
      over 15 years with a reduction of the gender gap in 2009. Antirheumatic
      medication was increasingly used over 15 years with no gender differences.
      CONCLUSIONS: RA patients reported statistically significantly improved health
      status for most PROs from 1994 to 2009. Women improved most, and although they
      still reported higher disease impact than men, the gender differences were small
      at the final data collection in 2009.

PMID- 24130266
TI  - Evidence for oesophageal and anorectal involvement in very early systemic
      sclerosis (VEDOSS): report from a single VEDOSS/EUSTAR centre.
AB  - BACKGROUND: The oesophagus is the first gastrointestinal (GI) tract involved in
      systemic sclerosis (SSc), followed by the anorectum. OBJECTIVE: Evaluation of
      oesophageal and anorectal involvement and their correlations in patients with
      very early diagnosis of SSc (VEDOSS). PATIENTS AND METHODS: 59 patients with
      VEDOSS, evaluated with oesophageal and anorectal manometry and investigated with
      lung function tests and chest HRCT. Demographic data, oesophageal and anorectal
      symptoms, Raynaud's phenomenon, autoantibodies, videocapillaroscopy patterns,
      puffy fingers and digital ulcers were recorded for all patients. RESULTS: In 4
      patients oesophageal manometry and in 17 patients anorectal manometry was not
      performed because of scarce tolerance. Oesophageal peristalsis was absent in 14
      patients; its pressure and speed were significantly lower in 41 patients (p<0.001
      and p=0.005, respectively). The maximum pressure and mean pressure (Pmax and Pm)
      of lower oesophageal sphincter were significantly lower (p=0.012 and p=0.024,
      respectively). Patients with a diffusing capacity of the lung for carbon
      monoxide<80% presented a hypotonic lower oesophageal sphincter (p=0.008) and an
      abnormal peristalsis (p<0.001); patients with a diffusing capacity of the lung
      for carbon monoxide>80% showed only an abnormal peristalsis (<0.001). The anal
      resting pressure (ARP) at 4.3 cm and 2 cm from anal edge and the anal canal Pm
      were significantly decreased (p<0.001 and p=0.010, respectively). The maximum
      voluntary contraction was significantly abnormal in its Pmax and Pm (p=0.017 and
      p=0.005) and in its duration (p=0.001). In patients with a positive HRCT, the ARP
      and the canal Pmax and Pm were significantly lower; patients with negative HRCT
      presented only an abnormal ARP. CONCLUSIONS: In patients with VEDOSS, oesophageal
      and anorectal disorders are frequently detected, showing that very early SSc is
      characterised by GI involvement.

PMID- 24130268
TI  - A glimpse of the future.

PMID- 24130270
TI  - Pregnancy: window into women's future cardiovascular health.

PMID- 24130271
TI  - Preconception care: call for national guidelines.

PMID- 24130267
TI  - AMPA/kainate glutamate receptors contribute to inflammation, degeneration and
      pain related behaviour in inflammatory stages of arthritis.
AB  - OBJECTIVES: Synovial fluid glutamate concentrations increase in arthritis.
      Activation of kainate (KA) and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6
      (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA
      and KA GluRs are expressed in human arthritis, and that intra-articular NBQX
      (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced
      arthritis (AIA). METHODS: GluR immunohistochemistry was related to synovial
      inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis
      (RA). A single intra-articular NBQX injection was given at induction, and knee
      swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging,
      RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human
      primary osteoblast (HOB) activity were determined. RESULTS: AMPAR2 and KA1
      immunolocalised to remodelling bone, cartilage and synovial cells in human OA and
      RA, and rat AIA. All arthritic tissues showed degradation and synovial
      inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1-21),
      gait abnormalities (days 1-2), end-stage joint destruction (p<0.001), synovial
      inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05)
      and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and
      bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB
      number and prevented mineralisation. CONCLUSIONS: AMPA/KA GluRs are expressed in
      human OA and RA, and in AIA, where a single intra-articular injection of NBQX
      reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%,
      respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA
      GluR antagonists represent a potential treatment for arthritis.

PMID- 24130272
TI  - Facing the consequences of binge drinking.

PMID- 24130274
TI  - Driving: the other half of the equation.

PMID- 24130275
TI  - Online health: the end of family medicine?

PMID- 24130276
TI  - Concerns about referring patients to chiropractors.

PMID- 24130279
TI  - Adopted children from the former Soviet Union: are they at risk of fetal alcohol
      spectrum disorder?
AB  - QUESTION: One of the families in my practice is considering adoption of a 2-year
      old child from the former Soviet Union. The family has been reassured by the
      agency that a doctor will examine the child to rule out developmental delays.
      However, my understanding from your previous articles is that one cannot rule out
      fetal alcohol spectrum disorder (FASD) at that age. Are these children at
      increased risk of developing FASD? ANSWER: You are correct: FASD cannot be ruled
      out at 2 years of age. The risk of FASD, neglect, and abuse among children in
      orphanages in the former Soviet Union is high. While adoption of children with
      known developmental delays should be encouraged and supported, most families seek
      to adopt with the assumption that these children will be healthy.

PMID- 24130278
TI  - Approach to diagnosing celiac disease in patients with low bone mineral density
      or fragility fractures: multidisciplinary task force report.
AB  - OBJECTIVE: To provide clinicians with an update on the diagnosis of celiac
      disease (CD) and to make recommendations on the indications to screen for CD in
      patients presenting with low bone mineral density (BMD) or fragility fractures.
      QUALITY OF EVIDENCE: A multidisciplinary task force developed clinically relevant
      questions related to the diagnosis of CD as the basis for a literature search of
      the MEDLINE, EMBASE, and CENTRAL databases (January 2000 to January 2009) using
      the key words celiac disease, osteoporosis, osteopenia, low bone mass, and
      fracture. The existing literature consists of level I and II studies. MAIN
      MESSAGE: The estimated prevalence of asymptomatic CD is 2% to 3% in individuals
      with low BMD. Routine screening for CD is not justified in patients with low BMD.
      However, targeted screening for CD is recommended for patients who have T-scores
      of -1.0 or less at the spine or hip, or a history of fragility fractures in
      association with any CD-related symptoms or conditions; family history of CD; or
      low urinary calcium levels, vitamin D insufficiency, and raised parathyroid
      hormone levels despite adequate intake of calcium and vitamin D. Celiac disease
      testing should be performed while the subject is consuming a gluten-containing
      diet; initial screening should be performed with human recombinant immunoglobulin
      (Ig) A tissue transglutaminase or other IgA tissue transglutaminase assays, in
      association with IgA endomysial antibody immunofluorescence. Duodenal biopsy is
      necessary to confirm the diagnosis of CD. Human leukocyte antigen typing might
      assist in confirming or ruling out the diagnosis of CD in cases where serology
      and histology are discordant. Definitive diagnosis is based on clinical,
      serologic, and histologic features, combined with a positive response to a gluten
      free diet. CONCLUSION: Current evidence does not support routine screening for CD
      in all patients with low BMD. A targeted case-finding approach is appropriate for
      patients who are at higher risk of CD.

PMID- 24130280
TI  - Acetaminophen in children: an old drug with new warnings.
AB  - QUESTION: I frequently suggest to parents to use acetaminophen to treat their
      children's fever and pain. Recently, I had a child in my office who presented
      with a target-lesion skin rash a day after receiving acetaminophen. The rash
      resolved after 3 days and after stopping administration of acetaminophen. Does
      acetaminophen carry a risk of adverse events such as this? ANSWER: Like any other
      medication or active substance, acetaminophen preparations might carry a risk of
      adverse events. In recent years a potential association between acetaminophen and
      asthma was investigated, and the US Food and Drug Administration recently
      published a warning about potential severe but rare skin reactions associated
      with acetaminophen. Although acetaminophen is mostly a safe medication, health
      care providers should be alert and advise parents about the possibility of rare
      but severe adverse events.

PMID- 24130281
TI  - Two fractures of the lower extremity not to miss in the emergency department.

PMID- 24130282
TI  - Use of ASA after warfarin for unprovoked VTE.

PMID- 24130283
TI  - Unruptured vasa previa with anomalous umbilical cord formation: a case of
      postpartum physician tachycardia.

PMID- 24130285
TI  - Dermacase. Can you identify this condition? Acanthosis nigricans.

PMID- 24130287
TI  - Dr William Osler and the Pictou County cattle disease.

PMID- 24130286
TI  - Decision making in family medicine: randomized trial of the effects of the
      InfoClinique and Trip database search engines.
AB  - OBJECTIVE: To compare the ability of users of 2 medical search engines,
      InfoClinique and the Trip database, to provide correct answers to clinical
      questions and to explore the perceived effects of the tools on the clinical
      decision-making process. DESIGN: Randomized trial. SETTING: Three family medicine
      units of the family medicine program of the Faculty of Medicine at Laval
      University in Quebec city, Que. PARTICIPANTS: Fifteen second-year family medicine
      residents. INTERVENTION: Residents generated 30 structured questions about
      therapy or preventive treatment (2 questions per resident) based on clinical
      encounters. Using an Internet platform designed for the trial, each resident
      answered 20 of these questions (their own 2, plus 18 of the questions formulated
      by other residents, selected randomly) before and after searching for information
      with 1 of the 2 search engines. For each question, 5 residents were randomly
      assigned to begin their search with InfoClinique and 5 with the Trip database.
      MAIN OUTCOME MEASURES: The ability of residents to provide correct answers to
      clinical questions using the search engines, as determined by third-party
      evaluation. After answering each question, participants completed a questionnaire
      to assess their perception of the engine's effect on the decision-making process
      in clinical practice. RESULTS: Of 300 possible pairs of answers (1 answer before
      and 1 after the initial search), 254 (85%) were produced by 14 residents. Of
      these, 132 (52%) and 122 (48%) pairs of answers concerned questions that had been
      assigned an initial search with InfoClinique and the Trip database, respectively.
      Both engines produced an important and similar absolute increase in the
      proportion of correct answers after searching (26% to 62% for InfoClinique, for
      an increase of 36%; 24% to 63% for the Trip database, for an increase of 39%; P =
      .68). For all 30 clinical questions, at least 1 resident produced the correct
      answer after searching with either search engine. The mean (SD) time of the
      initial search for each question was 23.5 (7.6) minutes with InfoClinique and
      22.3 (7.8) minutes with the Trip database (P = .30). Participants' perceptions of
      each engine's effect on the decision-making process were very positive and
      similar for both search engines. CONCLUSION: Family medicine residents' ability
      to provide correct answers to clinical questions increased dramatically and
      similarly with the use of both InfoClinique and the Trip database. These tools
      have strong potential to increase the quality of medical care.

PMID- 24130289
TI  - Teaching ethics in family medicine: introducing a faculty handbook.

PMID- 24130290
TI  - Documenting alcohol use in primary care in Alberta.

PMID- 24130291
TI  - The arts as a path to recovery.

PMID- 24130294
TI  - Looking on the past, thinking of the future: conversation with Paul Rainsberry.

PMID- 24130299
TI  - Contraceptive practices and attitudes among immigrant and nonimmigrant women in
      Canada.
AB  - OBJECTIVE: To compare experiences, attitudes, and beliefs of immigrant and
      nonimmigrant women presenting for abortion with regard to contraception, and to
      identify difficulties involved in accessing contraception in Canada. DESIGN: A
      survey of immigrant and nonimmigrant women asking about women's experiences with
      and attitudes toward contraceptives and any barriers to contraceptive access they
      have encountered. Demographic data including ethnicity, country of origin, and
      length of residence in Canada were collected. SETTING: Two urban abortion
      clinics. PARTICIPANTS: Women presenting for first-trimester abortion. MAIN
      OUTCOME MEASURES: Type of contraception used when the unwanted pregnancy was
      conceived, attitudes to contraceptives, and barriers to access of contraceptives.
      RESULTS: A total of 999 women completed questionnaires during the study period
      (75.9% response rate); 466 of them (46.6%) were born in Canada. Immigrant women
      presenting for abortion were less likely to be using hormonal contraception when
      they got pregnant (12.5% vs 23.5%, P < .001) and had more negative attitudes
      toward hormonal contraception (62.6% vs 51.6%, P < .003). They reported having
      more difficulties accessing contraception before the abortion (24.8% vs 15.3%, P
      < .001) than nonimmigrant women did. About half of all the women expressed fear
      about intrauterine device use. The longer immigrant women had lived in Canada,
      the more likely they were to have similar responses to those of Canadian-born
      women. CONCLUSION: The information provided by this study might be valuable for
      family doctors and other clinicians to improve contraceptive information
      resources for immigrants to address existing knowledge gaps and other culturally
      relevant concerns. As about half of all women presenting for abortion expressed
      negative attitudes toward the more effective methods of contraception, it is
      important that family doctors educate all women at risk for unintended
      pregnancies.

PMID- 24130300
TI  - Family practice versus specialist care for low-risk obstetrics: examining patient
      satisfaction in Newfoundland and Labrador.
AB  - OBJECTIVE: To investigate patient satisfaction with 3 models of low-risk
      obstetrics care: solo care by a GP, group care by GPs, and specialist care.
      DESIGN: Three-arm study comparing results of a self-administered, anonymous
      questionnaire. SETTING: Two academic family practices and the labour and delivery
      ward in St John's, Nfld. PARTICIPANTS: A total of 220 women deemed to have low
      risk pregnancies; 82 women completed the questionnaire (37% response rate). MAIN
      OUTCOME MEASURES: Patient satisfaction scores obtained from a modified version of
      the Patient Expectations and Satisfaction with Prenatal Care instrument. RESULTS:
      Low-risk maternity patients' satisfaction with obstetric care provided by GPs in
      a group-care setting was equivalent to that with obstetric care provided by GPs
      working solo and greater than that with obstetric care provided by specialists.
      CONCLUSION: Patients found that group care by GPs was an acceptable means of
      receiving obstetric services in a low-risk setting. Therefore, a group practice
      model might provide an attractive means for FPs to keep obstetrics within the
      scope of primary care.

PMID- 24130301
TI  - Integrated care for pregnant women on methadone maintenance treatment: Canadian
      primary care cohort study.
AB  - OBJECTIVE: To describe the characteristics of a national cohort of pregnant women
      on methadone maintenance treatment (MMT) and to provide treatment outcome data
      for integrated care programs. DESIGN: Retrospective chart review. SETTING: Three
      different integrated care programs in geographically distinct cities: the Toronto
      Centre for Substance Use in Pregnancy in Toronto, Ont; the Herzl Family Practice
      Centre in Montreal, Que; and the Sheway clinic in Vancouver, BC. PARTICIPANTS:
      Pregnant women meeting criteria for opioid dependence and attending an integrated
      care program between 1997 and 2009. Women were excluded if they were on MMT only
      for chronic pain. MAIN OUTCOME MEASURES: Patient demographic characteristics,
      concurrent medical and psychiatric disorders, and substance use outcome data.
      RESULTS: A total of 102 opioid-dependent pregnancies were included. The mean age
      was 29.7 years and 64% of women were white. Women in Montreal were more likely to
      have partners and had fewer children. Differences in living and housing
      situations among the sites tended to resolve by the time of delivery. Almost half
      of this cohort tested positive for hepatitis C. Women had a high prevalence of
      depression and anxiety across all sites. Half of this cohort was on MMT before
      conception and for the other half, MMT was initiated at a mean gestational age of
      20.7 weeks, resulting in a mean dose of 82.4 mg at delivery. At the first visit,
      polysubstance use was common. Prescription opioid use was more frequent in
      Toronto and heroin use was more prevalent in Vancouver and Montreal. For the
      entire population, significant reductions were found by the time of delivery for
      illicit (P < .001) and prescription opioids (P = .001), cocaine (P < .001),
      marijuana (P = .009), and alcohol use (P < .001). CONCLUSION: Despite geographic
      differences, all 3 integrated care programs have been associated with significant
      decreases in substance use in pregnant opioid-dependent women.

PMID- 24130305
TI  - ORMAN: optimal resolution of ambiguous RNA-Seq multimappings in the presence of
      novel isoforms.
AB  - MOTIVATION: RNA-Seq technology is promising to uncover many novel alternative
      splicing events, gene fusions and other variations in RNA transcripts. For an
      accurate detection and quantification of transcripts, it is important to resolve
      the mapping ambiguity for those RNA-Seq reads that can be mapped to multiple
      loci: >17% of the reads from mouse RNA-Seq data and 50% of the reads from some
      plant RNA-Seq data have multiple mapping loci. In this study, we show how to
      resolve the mapping ambiguity in the presence of novel transcriptomic events such
      as exon skipping and novel indels towards accurate downstream analysis. We
      introduce ORMAN ( O ptimal R esolution of M ultimapping A mbiguity of R N A-Seq
      Reads), which aims to compute the minimum number of potential transcript products
      for each gene and to assign each multimapping read to one of these transcripts
      based on the estimated distribution of the region covering the read. ORMAN
      achieves this objective through a combinatorial optimization formulation, which
      is solved through well-known approximation algorithms, integer linear programs
      and heuristics. RESULTS: On a simulated RNA-Seq dataset including a random subset
      of transcripts from the UCSC database, the performance of several state-of-the
      art methods for identifying and quantifying novel transcripts, such as Cufflinks,
      IsoLasso and CLIIQ, is significantly improved through the use of ORMAN.
      Furthermore, in an experiment using real RNA-Seq reads, we show that ORMAN is
      able to resolve multimapping to produce coverage values that are similar to the
      original distribution, even in genes with highly non-uniform coverage.
      AVAILABILITY: ORMAN is available at http://orman.sf.net

PMID- 24130306
TI  - SecStAnT: secondary structure analysis tool for data selection, statistics and
      models building.
AB  - MOTIVATION: Atomistic or coarse grained (CG) potentials derived from statistical
      distributions of internal variables have recently become popular due to the need
      of simplified interactions for reaching larger scales in simulations or more
      efficient conformational space sampling. However, the process of parameterization
      of accurate and predictive statistics-based force fields requires a huge amount
      of work and is prone to the introduction of bias and errors. RESULTS: This
      article introduces SecStAnT, a software for the creation and analysis of protein
      structural datasets with user-defined primary/secondary structure composition,
      with a particular focus on the CG representation. In addition, the possibility of
      managing different resolutions and the primary/secondary structure selectivity
      allow addressing the mapping-backmapping of atomistic to CG representation and
      study the secondary to primary structure relations. Sample datasets and
      distributions are reported, including interpretation of structural features.
      AVAILABILITY AND IMPLEMENTATION: SecStAnT is available free of charge at
      secstant.sourceforge.net/. Source code is freely available on request,
      implemented in Java and supported on Linux, MS Windows and OSX.

PMID- 24130307
TI  - Comment on 'Bayesian parentage analysis with systematic accountability of
      genotyping error, missing data and false matching'.
AB  - We show the software SOLOMON is improved by using the likelihood ratio instead of
      an ad hoc statistic. CODE:  github.com/eriqande/solidmon/releases/tag/v0.1
      bioinformatics

PMID- 24130308
TI  - FFAS-3D: improving fold recognition by including optimized structural features
      and template re-ranking.
AB  - MOTIVATION: Homology detection enables grouping proteins into families and
      prediction of their structure and function. The range of application of homology
      based predictions can be significantly extended by using sequence profiles and
      incorporation of local structural features. However, incorporation of the latter
      terms varies a lot between existing methods, and together with many examples of
      distant relations not recognized even by the best methods, suggests that further
      improvements are still possible. RESULTS: Here we describe recent improvements to
      the fold and function assignment system (FFAS) method, including adding optimized
      structural features (experimental or predicted), 'symmetrical' Z-score
      calculation and re-ranking the templates with a neural network. The alignment
      accuracy in the new FFAS-3D is now 11% higher than the original and comparable
      with the most accurate template-based structure prediction algorithms. At the
      same time, FFAS-3D has high success rate at the Structural Classification of
      Proteins (SCOP) family, superfamily and fold levels. Importantly, FFAS-3D results
      are not highly correlated with other programs suggesting that it may
      significantly improve meta-predictions. FFAS-3D does not require 3D structures of
      the templates, as using predicted features instead of structure-derived does not
      lead to the decrease of accuracy. Because of that, FFAS-3D can be used for
      databases other than Protein Data Bank (PDB) such as Protein families database or
      Clusters of orthologous groups thus extending its applications to functional
      annotations of genomes and protein families. AVAILABILITY AND IMPLEMENTATION:
      FFAS-3D is available at http://ffas.godziklab.org.

PMID- 24130309
TI  - De novo finished 2.8 Mbp Staphylococcus aureus genome assembly from 100 bp short
      and long range paired-end reads.
AB  - MOTIVATION: Paired-end sequencing allows circumventing the shortness of the reads
      produced by second generation sequencers and is essential for de novo assembly of
      genomes. However, obtaining a finished genome from short reads is still an open
      challenge. We present an algorithm that exploits the pairing information issued
      from inserts of potentially any length. The method determines paths through an
      overlaps graph by using a constrained search tree. We also present a method that
      automatically determines suited overlaps cutoffs according to the contextual
      coverage, reducing thus the need for manual parameterization. Finally, we
      introduce an interactive mode that allows querying an assembly at targeted
      regions. RESULTS: We assess our methods by assembling two Staphylococcus aureus
      strains that were sequenced on the Illumina platform. Using 100 bp paired-end
      reads and minimal manual curation, we produce a finished genome sequence for the
      previously undescribed isolate SGH-10-168. AVAILABILITY AND IMPLEMENTATION: The
      presented algorithms are implemented in the standalone Edena software, freely
      available under the General Public License (GPLv3) at www.genomic.ch/edena.php.

PMID- 24130310
TI  - Aboriginal populations and youth suicide.

PMID- 24130311
TI  - Aboriginal populations and youth suicide.

PMID- 24130312
TI  - Deathless models of aging: time to reform CanMEDS.

PMID- 24130313
TI  - CrossTalk proposal: Prolonged intense exercise training does lead to myocardial
      damage.

PMID- 24130314
TI  - CrossTalk opposing view: Prolonged intense exercise does not lead to cardiac
      damage.

PMID- 24130315
TI  - Rebuttal from Eduard Guasch and Stanley Nattel.

PMID- 24130316
TI  - Rebuttal from Jonatan R. Ruiz, Michael Joyner and Alejandro Lucia.

PMID- 24130317
TI  - Lipid metabolism in contracting muscle--HSL takes a back seat.

PMID- 24130318
TI  - Food for thought--resveratrol vs. exercise training.

PMID- 24130319
TI  - Obesity and plasticity: how your gut learns to deal with your diet.

PMID- 24130320
TI  - Steroids and antioxidants: a neonatal cocktail for saving your adult heart?

PMID- 24130321
TI  - The cerebovasculature: a smooth (muscle) operator?

PMID- 24130322
TI  - Ranolazine's sweet side--improvement of glycaemic control by the novel mechanism
      of skeletal muscle microvascular recruitment.

PMID- 24130323
TI  - Recent data do not provide evidence that resveratrol causes 'mainly negative' or
      'adverse' effects on exercise training in humans.

PMID- 24130324
TI  - Reply from Lasse Gliemann, Jakob Schmidt, Jesper Olesen, Rasmus Sjorup Bienso,
      Sebastian Louis Peronard, Simon Udsen Grandjean, Stefan Peter Mortensen, Michael
      Nyberg, Jens Bangsbo, Henriette Pilegaard and Ylva Hellsten.

PMID- 24130326
TI  - An interview with Janet Rossant. Interview by Catarina Vicente.

PMID- 24130327
TI  - To branch or not to branch: the role of pre-patterning in lateral root formation.
AB  - The establishment of a pre-pattern or competence to form new organs is a key
      feature of the postembryonic plasticity of plant development, and the elaboration
      of such pre-patterns leads to remarkable heterogeneity in plant form. In root
      systems, many of the differences in architecture can be directly attributed to
      the outgrowth of lateral roots. In recent years, efforts have focused on
      understanding how the pattern of lateral roots is established. Here, we review
      recent findings that point to a periodic mechanism for establishing this pattern,
      as well as roles for plant hormones, particularly auxin, in the earliest steps
      leading up to lateral root primordium development. In addition, we compare the
      development of lateral root primordia with in vitro plant regeneration and
      discuss possible common molecular mechanisms. 

PMID- 24130328
TI  - Derivation of lung mesenchymal lineages from the fetal mesothelium requires
      hedgehog signaling for mesothelial cell entry.
AB  - Recent studies have shown that mesothelial progenitors contribute to mesenchymal
      lineages of developing organs. To what extent the overlying mesothelium
      contributes to lung development remains unknown. To rigorously address this
      question, we employed Wt1(CreERT2/+) mice for high-fidelity lineage tracing after
      confirming that Cre recombinase was mesothelial specific and faithfully
      recapitulated endogenous Wilms' tumor 1 (Wt1) gene expression. We visualized
      WT1(+) mesothelial cell entry into the lung by live imaging and identified their
      progenies in subpopulations of bronchial smooth muscle cells, vascular smooth
      muscle cells and desmin(+) fibroblasts by lineage tagging. Derivation of these
      lineages was only observed with Cre recombinase activation during early lung
      development. Using loss-of-function assays in organ cultures, and targeted
      mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that
      mesothelial cell movement into the lung requires the direct action of hedgehog
      signaling. By contrast, hedgehog signaling was not required for fetal mesothelial
      heart entry. These findings further support a paradigm wherein the mesothelium is
      a source of progenitors for mesenchymal lineages during organogenesis and
      indicate that signals controlling mesothelial cell entry are organ specific. 

PMID- 24130329
TI  - Rapid identification of kidney cyst mutations by whole exome sequencing in
      zebrafish.
AB  - Forward genetic approaches in zebrafish have provided invaluable information
      about developmental processes. However, the relative difficulty of mapping and
      isolating mutations has limited the number of new genetic screens. Recent
      improvements in the annotation of the zebrafish genome coupled to a reduction in
      sequencing costs prompted the development of whole genome and RNA sequencing
      approaches for gene discovery. Here we describe a whole exome sequencing (WES)
      approach that allows rapid and cost-effective identification of mutations. We
      used our WES methodology to isolate four mutations that cause kidney cysts; we
      identified novel alleles in two ciliary genes as well as two novel mutants. The
      WES approach described here does not require specialized infrastructure or
      training and is therefore widely accessible. This methodology should thus help
      facilitate genetic screens and expedite the identification of mutants that can
      inform basic biological processes and the causality of genetic disorders in
      humans. 

PMID- 24130330
TI  - Artificial three-dimensional niches deconstruct pancreas development in vitro.
AB  - In the context of a cellular therapy for diabetes, methods for pancreatic
      progenitor expansion and subsequent differentiation into insulin-producing beta
      cells would be extremely valuable. Here we establish three-dimensional culture
      conditions in Matrigel that enable the efficient expansion of dissociated mouse
      embryonic pancreatic progenitors. By manipulating the medium composition we
      generate either hollow spheres, which are mainly composed of pancreatic
      progenitors, or complex organoids that spontaneously undergo pancreatic
      morphogenesis and differentiation. The in vitro maintenance and expansion of
      pancreatic progenitors require active Notch and FGF signaling, thus
      recapitulating in vivo niche signaling interactions. Our experiments reveal new
      aspects of pancreas development, such as a community effect by which small groups
      of cells better maintain progenitor properties and expand more efficiently than
      isolated cells, as well as the requirement for three-dimensionality. Finally,
      growth conditions in chemically defined biomaterials pave the way for testing the
      biophysical and biochemical properties of the niche that sustains pancreatic
      progenitors. 

PMID- 24130331
TI  - Endothelial cells from visceral adipose tissue disrupt adipocyte functions in a
      three-dimensional setting: partial rescue by angiopoietin-1.
AB  - During obesity, chronic inflammation of human white adipose tissue (WAT) is
      associated with metabolic and vascular alterations. Endothelial cells from
      visceral WAT (VAT-ECs) exhibit a proinflammatory and senescent phenotype and
      could alter adipocyte functions. We aimed to determine the contribution of VAT
      ECs to adipocyte dysfunction related to inflammation and to rescue these
      alterations by anti-inflammatory strategies. We developed an original three
      dimensional setting allowing maintenance of unilocular adipocyte functions.
      Coculture experiments demonstrated that VAT-ECs provoked a decrease in the
      lipolytic activity, adipokine secretion, and insulin sensitivity of adipocytes
      from obese subjects, as well as an increased production of several inflammatory
      molecules. Interleukin (IL)-6 and IL-1beta were identified as potential actors in
      these adipocyte alterations. The inflammatory burst was not observed in
      cocultured cells from lean subjects. Interestingly, pericytes, in functional
      interactions with ECs, exhibited a proinflammatory phenotype with diminished
      angiopoietin-1 (Ang-1) secretion in WAT from obese subjects. Using the anti
      inflammatory Ang-1, we corrected some deleterious effects of WAT-ECs on
      adipocytes, improving lipolytic activity and insulin sensitivity and reducing the
      secretion of proinflammatory molecules. In conclusion, we identified a negative
      impact of VAT-ECs on adipocyte functions during human obesity. Therapeutic
      options targeting EC inflammation could prevent adipocyte alterations that
      contribute to obesity comorbidities. 

PMID- 24130332
TI  - BMI, RQ, diabetes, and sex affect the relationships between amino acids and clamp
      measures of insulin action in humans.
AB  - Previous studies have used indirect measures of insulin sensitivity to link
      circulating amino acids with insulin resistance and identify potential biomarkers
      of diabetes risk. Using direct measures (i.e., hyperinsulinemic-euglycemic
      clamps), we examined the relationships between the metabolomic amino acid profile
      and insulin action (i.e., glucose disposal rate [GDR]). Relationships between GDR
      and serum amino acids were determined among insulin-sensitive, insulin-resistant,
      and type 2 diabetic (T2DM) individuals. In all subjects, glycine (Gly) had the
      strongest correlation with GDR (positive association), followed by
      leucine/isoleucine (Leu/Ile) (negative association). These relationships were
      dramatically influenced by BMI, the resting respiratory quotient (RQ), T2DM, and
      sex. Gly had a strong positive correlation with GDR regardless of BMI, RQ, or sex
      but became nonsignificant in T2DM. In contrast, Leu/Ile was negatively associated
      with GDR in nonobese and T2DM subjects. Increased resting fat metabolism (i.e.,
      low RQ) and obesity were observed to independently promote and negate the
      association between Leu/Ile and insulin resistance, respectively. Additionally,
      the relationship between Leu/Ile and GDR was magnified in T2DM males. Future
      studies are needed to determine whether Gly has a mechanistic role in glucose
      homeostasis and whether dietary Gly enrichment may be an effective intervention
      in diseases characterized by insulin resistance. 

PMID- 24130333
TI  - G0-G1 transition and the restriction point in pancreatic beta-cells in vivo.
AB  - Most of our knowledge on cell kinetics stems from in vitro studies of
      continuously dividing cells. In this study, we determine in vivo cell-cycle
      parameters of pancreatic beta-cells, a largely quiescent population, using drugs
      that mimic or prevent glucose-induced replication of beta-cells in mice.
      Quiescent beta-cells exposed to a mitogenic glucose stimulation require 8 h to
      enter the G1 phase of the cell cycle, and this time is prolonged in older age.
      The duration of G1, S, and G2/M is ~5, 8, and 6 h, respectively. We further
      provide the first in vivo demonstration of the restriction point at the G0-G1
      transition, discovered by Arthur Pardee 40 years ago. The findings may have
      pharmacodynamic implications in the design of regenerative therapies aimed at
      increasing beta-cell replication and mass in patients with diabetes.

PMID- 24130334
TI  - Generation of L cells in mouse and human small intestine organoids.
AB  - Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), a
      powerful stimulant of insulin release. Strategies to augment endogenous GLP-1
      production include promoting L-cell differentiation and increasing L-cell number.
      Here we present a novel in vitro platform to generate functional L cells from
      three-dimensional cultures of mouse and human intestinal crypts. We show that
      short-chain fatty acids selectively increase the number of L cells, resulting in
      an elevation of GLP-1 release. This is accompanied by the upregulation of
      transcription factors associated with the endocrine lineage of intestinal stem
      cell development. Thus, our platform allows us to study and modulate the
      development of L cells in mouse and human crypts as a potential basis for novel
      therapeutic strategies in patients with type 2 diabetes. 

PMID- 24130335
TI  - FTO genotype, vitamin D status, and weight gain during childhood.
AB  - Previous evidence suggests that variants in the fat mass and obesity-associated
      gene (FTO) affect adiposity in an age-dependent fashion in children, and
      nutritional factors may modify genotype effects. We assessed the effect of FTO
      rs9939609 on BMI and BMI-for-age Z score changes during childhood in a population
      based longitudinal study in the Brazilian Amazon and investigated whether these
      effects were modified by vitamin D status, an important nutritional factor
      related to adiposity. At baseline, 1,088 children aged <10 years had complete
      genotypic and anthropometric data; 796 were followed up over a median 4.6 years.
      Baseline vitamin D insufficiency was defined as <75 nmol/L. We observed a 0.07
      kg/m(2)/year increase in BMI and a 0.03 Z/year increase in BMI-for-age Z score
      per rs9939609 risk allele over follow-up (P = 0.01). Vitamin D status
      significantly modified FTO effects (P for interaction = 0.02). The rs9939609 risk
      allele was associated with a 0.05 Z/year increase in BMI-for-age Z score among
      vitamin D-insufficient children (P = 0.003), while no significant genetic effects
      were observed among vitamin D-sufficient children. Our data suggest that FTO
      rs9939609 affects child weight gain, and genotype effects are more pronounced
      among children with insufficient vitamin D levels. 

PMID- 24130336
TI  - RNA-binding protein PTB and microRNA-221 coregulate AdipoR1 translation and
      adiponectin signaling.
AB  - Adiponectin receptor 1 (AdipoR1) mediates adiponectin's pleiotropic effects in
      muscle and liver and plays an important role in the regulation of insulin
      resistance and diabetes. Here, we demonstrate a pivotal role for microRNA-221
      (miR-221) and the RNA-binding protein polypyrimidine tract-binding protein (PTB)
      in posttranscriptional regulation of AdipoR1 during muscle differentiation and in
      obesity. RNA-immunoprecipitation and luciferase reporter assays illustrated that
      both PTB and miR-221 bind AdipoR1-3'UTR and cooperatively inhibit AdipoR1
      translation. Depletion of PTB or miR-221 increased, while overexpression of these
      factors decreased, AdipoR1 protein synthesis in both muscle and liver cells.
      During myogenesis, downregulation of PTB and miR-221 robustly induced AdipoR1
      translation, providing a mechanism for enhanced AdipoR1 protein expression and
      activation in differentiated muscle cells. In addition, since both PTB and miR
      221 are upregulated in liver and muscle of genetic and dietary mouse models of
      obesity, this novel translational mechanism may be at least partly responsible
      for the reduction in AdipoR1 protein levels in obesity. These findings highlight
      the importance of translational control in regulating AdipoR1 protein expression
      and adiponectin signaling. Given that adiponectin is reduced in obesity,
      induction of AdipoR1 could potentially enhance adiponectin beneficial effects and
      ameliorate insulin resistance and diabetes. 

PMID- 24130337
TI  - Obesity alters adipose tissue macrophage iron content and tissue iron
      distribution.
AB  - Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation
      of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies
      have implicated recruited M1 ATMs in the metabolic consequences of obesity;
      however, little is known regarding the role of alternatively activated resident
      M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we
      report the discovery of a population of alternatively activated ATMs with
      elevated cellular iron content and an iron-recycling gene expression profile.
      These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are
      referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this
      percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages.
      Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity.
      In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression
      of iron importers as well as the iron exporter, ferroportin, suggesting an
      impaired ability to handle iron. In vitro, exposure of primary peritoneal
      macrophages to saturated fatty acids also alters iron metabolism gene expression.
      Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron
      overload in obese mice. In conclusion, in obesity, iron distribution is altered
      both at the cellular and tissue levels, with AT playing a predominant role in
      this change. An increased availability of fatty acids during obesity may
      contribute to the observed changes in MFe(hi) ATM phenotype and their reduced
      capacity to handle iron. 

PMID- 24130338
TI  - Insulin regulates the unfolded protein response in human adipose tissue.
AB  - Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be
      a major contributor to many obesity-related pathologies. Little is known about
      what causes ER stress in obese people. Here, we show that insulin upregulated the
      unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in
      3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic
      subjects, where it increased the UPR dose dependently over the entire physiologic
      insulin range (from ~ 35 to ~ 1,450 pmol/L). The insulin-induced UPR was not due
      to increased glucose uptake/metabolism and oxidative stress. It was associated,
      however, with increased protein synthesis, with accumulation of ubiquitination
      associated proteins, and with multiple posttranslational protein modifications
      (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations),
      some of which are potential causes for ER stress. These results reveal a new
      physiologic role of insulin and provide a putative mechanism for the development
      of ER stress in obesity. They may also have clinical and therapeutic
      implications, e.g., in diabetic patients treated with high doses of insulin.

PMID- 24130339
TI  - Mussels' sticky feet lead to applications.

PMID- 24130341
TI  - Poor glycemic control is a major factor in the overestimation of glomerular
      filtration rate in diabetic patients.
AB  - OBJECTIVE Serum creatinine levels are lower in diabetic patients compared with
      their nondiabetic counterparts. Therefore, estimated glomerular filtration rate
      (eGFR) is higher in the former than in the latter group. Factors associated with
      overestimation of renal function in diabetic patients were examined, and new
      formulae reflecting precise eGFR were created. RESEARCH DESIGN AND METHODS Eighty
      subjects (age 56.5 +/- 15.4 years; 35 males [43.8%]; 40 patients with diabetes
      and 40 nondiabetic subjects) were enrolled. GFR was evaluated by inulin clearance
      (Cin). eGFR values were calculated based on serum creatinine and/or serum
      cystatin C levels. The factors related to the dissociation between eGFR and Cin
      in diabetic patients and the agreement among each of three eGFR and Cin were
      compared. RESULTS Although Cin was not significantly different between the
      diabetic and nondiabetic subjects (P = 0.2866), each of three eGFR measures from
      the diabetic patients was significantly higher than that of the nondiabetic
      subjects (P < 0.01). There were significant and positive correlations between the
      ratio of each eGFR/Cin, hemoglobin A1c, and glycated albumin. The intraclass
      correlation coefficients in diabetic patients were weaker than those in the
      nondiabetic subjects, and the intercepts of the regression lines between each
      eGFR measure and Cin in the diabetic patients were significantly higher than
      those of the nondiabetic subjects. New formulae for the calculation of eGFR
      corrected by the glycemic control indices were better than the original eGFR,
      particularly in diabetic patients. CONCLUSIONS eGFR overestimates Cin as glycemic
      controls worsen. eGFR corrected by hemoglobin A1c is considered to be clinically
      useful and feasible. 

PMID- 24130342
TI  - Decreased circulatory response to hypovolemic stress in young women with type 1
      diabetes.
AB  - OBJECTIVE: Diabetes is associated with hemodynamic instability during different
      situations involving acute circulatory stress in daily life. Young men with type
      1 diabetes have been shown to have impaired circulatory response to hypovolemic
      stress. The effect of type 1 diabetes on cardiovascular response to hypovolemia
      in young women is unknown, however. RESEARCH DESIGN AND METHODS: Lower body
      negative pressure of 30 cm H2O was used to create rapid hypovolemic stress in 15
      young women with type 1 diabetes (DW) and 16 healthy women (control subjects
      [C]). Compensatory mobilization of venous capacitance blood (capacitance
      response) and net fluid absorption from tissue to blood were measured with a
      volumetric technique. Overall cardiovascular responses and plasma norepinephrine
      levels were measured. RESULTS: Capacitance response was reduced (DW, 0.67 +/-
      0.05; C, 0.92 +/- 0.06) and developed slower in DW (P < 0.01). Capacitance
      response was further reduced with increasing levels of HbA1c. Fluid absorption
      was almost halved in DW (P < 0.01). The initial vasoconstrictor response was
      reduced and developed slower in DW (P < 0.05). Arterial vasoconstriction was
      further reduced in the presence of microvascular complications (P < 0.05).
      CONCLUSIONS: DW present with decreased and slower mobilization of venous
      capacitance blood and decreased net fluid absorption from tissue to blood during
      hypovolemic circulatory stress. Collectively, this indicates that DW are prone to
      hemodynamic instability, especially in the presence of microvascular
      complications and poor glycemic control.

PMID- 24130343
TI  - Long-term effects of the booster-enhanced READY-Girls preconception counseling
      program on intentions and behaviors for family planning in teens with diabetes.
AB  - OBJECTIVE: To examine 12-month effects of a booster-enhanced preconception
      counseling (PC) program (READY-Girls) on family planning for teen girls with type
      1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants 13-19 years of
      age (n = 109) were randomized to a standard care control group (CG) or
      intervention group (IG) that received PC over three consecutive clinic visits.
      Prepost data were collected at baseline, 3- and 6-month booster sessions, and a
      12-month follow-up visit. RESULTS: Mean age was 15.8 years; 9 (8%) subjects had
      type 2 diabetes; and 18 (17%) subjects were African American. At baseline, 20% (n
      = 22 of 109) had been sexually active, and of these, 50% (n = 11) had at least
      one episode of unprotected sex. Over time, IG participants retained greater PC
      knowledge (F[6, 541] = 4.05, P = 0.0005) and stronger intentions regarding PC
      (significant group-by-time effects) especially after boosters. IG participants
      had greater intentions to discuss PC (F[6, 82.4] = 2.56, P = 0.0254) and BC (F[6,
      534] = 3.40, P = 0.0027) with health care providers (HCPs) and seek PC when
      planning a pregnancy (F[6, 534] = 2.58, P = 0.0180). Although not significant, IG
      participants, compared with CG, showed a consistent trend toward lower rates of
      overall sexual activity over time: less sexual debut (35 vs. 41%) and higher
      rates of abstinence (44 vs. 32%). No pregnancies were reported in either group
      throughout the study. CONCLUSIONS: READY-Girls appeared to have long-term
      sustaining effects on PC knowledge, beliefs, and intentions to initiate
      discussion with HCPs that could improve reproductive health behaviors and
      outcomes. Strong boosters and providing PC at each clinic visit could play
      important roles in sustaining long-term effects.

PMID- 24130344
TI  - Poor glycemic control is related to increased nitric oxide activity within the
      renal circulation of patients with type 2 diabetes.
AB  - OBJECTIVE: Experimental studies have shown that glucose releases endothelial
      nitric oxide (NO) and that NO contributes to renal hyperperfusion in models of
      diabetes. To examine whether this translates into the human condition, we studied
      the relationship between glycemic control and renal NO activity in patients with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 113 patients with type 2
      diabetes and a wide range of HbA1c concentrations were included. Renal plasma
      flow (RPF) and glomerular filtration rate (GFR) were determined by constant
      infusion input clearance. Functional NO activity in the renal circulation was
      determined as change of RPF to infusion of the NO synthase (NOS) inhibitor N(G)
      monomethyl-L-arginine (L-NMMA) (4.25 mg/kg). As additional markers, we measured
      urinary excretion of NO (UNOx) and L-arginine-to-asymmetrical dimethylarginine
      (ADMA) ratio in plasma. RESULTS: Subjects within the highest tertile of HbA1c
      concentration had increased RPF (low, medium, and high tertiles 576 +/- 17 vs.
      585 +/- 22 vs. 627 +/- 33 mL/min/m(2), P = 0.05 by one-way ANOVA), while GFR was
      similar across tertiles. The response of RPF to NOS blockade was augmented in
      subjects with higher HbA1c levels (-55 +/- 7 vs. -64 +/- 8 vs. -86 +/- 8 mL/min,
      P = 0.04 by one-way ANOVA). Further, L-arginine-to-ADMA ratio and UNOx were
      increased in subjects with higher HbA1c levels. CONCLUSIONS: In line with
      experimental evidence, we could demonstrate in humans that poor glycemic control
      is related to higher NO activity and hyperperfusion of the kidney. The renal NO
      system may thus be a novel therapeutic target for improving renal hemodynamics in
      patients with diabetes.

PMID- 24130346
TI  - Earlier onset of complications in youth with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the risk of complications in youth with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Population-based cohorts of 342 youth (1-18 years of
      age) with prevalent type 2 diabetes, 1,011 youth with type 1 diabetes, and 1,710
      nondiabetic control youth were identified between 1986 and 2007 from a clinical
      registry and linked to health care records to assess long-term outcomes using ICD
      9CM and ICD-10CA codes. RESULTS: Youth with type 2 diabetes had an increased risk
      of any complication (hazard ratio 1.47 [95% CI 1.02-2.12]). Significant adverse
      clinical factors included age at diagnosis (1.08 [1.02-2.12]), HbA1c (1.06 [1.01
      1.12]), and, surprisingly, renin-angiotensin-aldosterone system (RAAS) inhibitor
      use (1.75 [1.27-2.41]). HNF-1alpha G319S polymorphism was protective in the type
      2 diabetes cohort (0.58 [0.34-0.99]). Kaplan-Meier statistics revealed an earlier
      diagnosis of renal and neurologic complications in the type 2 diabetes cohort,
      manifesting within 5 years of diagnosis. No difference in retinopathy was seen.
      Cardiovascular and cerebrovascular diseases were rare; however, major
      complications (dialysis, blindness, or amputation) started to manifest 10 years
      after diagnosis in the type 2 diabetes cohort. Youth with type 2 diabetes had
      higher rates of all outcomes than nondiabetic control youth and an overall 6.15
      fold increased risk of any vascular disease. CONCLUSIONS: Youth with type 2
      diabetes exhibit complications sooner than youth with type 1 diabetes. Younger
      age at diagnosis is potentially protective, and glycemic control is an important
      modifiable risk factor. The unexpected adverse association between RAAS inhibitor
      use and outcome is likely a confounder by indication; however, further evaluation
      in young people is warranted.

PMID- 24130345
TI  - The association between dietary flavonoid and lignan intakes and incident type 2
      diabetes in European populations: the EPIC-InterAct study.
AB  - OBJECTIVE: To study the association between dietary flavonoid and lignan intakes,
      and the risk of development of type 2 diabetes among European populations.
      RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer
      and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes
      cases and a stratified subcohort of 16,154 participants from among 340,234
      participants with 3.99 million person-years of follow-up in eight European
      countries. At baseline, country-specific validated dietary questionnaires were
      used. A flavonoid and lignan food composition database was developed from the
      Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of
      Agriculture databases. Hazard ratios (HRs) from country-specific Prentice
      weighted Cox regression models were pooled using random-effects meta-analysis.
      RESULTS: In multivariable models, a trend for an inverse association between
      total flavonoid intake and type 2 diabetes was observed (HR for the highest vs.
      the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not
      with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid
      subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and
      flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3
      ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated
      with a significantly reduced hazard of diabetes. CONCLUSIONS: Prospective
      findings in this large European cohort demonstrate inverse associations between
      flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes.
      This suggests a potential protective role of eating a diet rich in flavonoids, a
      dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.

PMID- 24130347
TI  - Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis:
      a randomized comparative trial.
AB  - OBJECTIVE: No prospective trials have been carried out comparing antibiotic
      treatment alone with primarily surgical treatment in patients with diabetes and
      foot osteomyelitis. The aim of the current study was to compare the outcomes of
      the treatment of diabetic foot osteomyelitis in patients treated exclusively with
      antibiotics versus patients who underwent conservative surgery, following up the
      patients for a period of 12 weeks after healing. RESEARCH DESIGN AND METHODS:
      Between 1 January 2010 and 31 December 2012, a prospective randomized comparative
      trial (clinical trial reg. no. NCT01137903, clinicaltrials.gov) of patients with
      diabetes who had received a diagnosis of neuropathic foot ulcers complicated by
      osteomyelitis was carried out at the Diabetic Foot Unit at the Complutense
      University of Madrid. Patients were randomized into the following two groups: the
      antibiotics group (AG) and the surgical group (SG). Antibiotics were given for a
      period of 90 days in the AG. Patients in the SG received conservative surgery
      with postoperative antibiotic treatment for 10 days. RESULTS: Eighteen patients
      (75%) achieved primary healing in the AG, and 19 (86.3%) in the SG (P = 0.33).
      The median time to healing was 7 weeks (quartile [Q] 1 to Q5, Q3-Q8) in the AG
      and 6 weeks (Q1-Q3, Q3-Q9) in the SG (P = 0.72). The conditions of four patients
      from the AG worsened (16.6%), and they underwent surgery. Three patients from the
      SG required reoperation. No difference was found between the two groups regarding
      minor amputations (P = 0.336). CONCLUSIONS: Antibiotic therapy and surgical
      treatment had similar outcomes in terms of healing rates, time to healing, and
      short-term complications in patients with neuropathic forefoot ulcers complicated
      by osteomyelitis without ischemia or necrotizing soft tissue infections.

PMID- 24130348
TI  - Total and cause-specific mortality by elevated transferrin saturation and
      hemochromatosis genotype in individuals with diabetes: two general population
      studies.
AB  - OBJECTIVE: Mortality is increased in patients with hereditary hemochromatosis, in
      individuals from the general population with increased transferrin saturation
      (TS), and also in patients with type 1 diabetes and increased TS from a highly
      specialized diabetes clinic. Thus, we have recommended targeted screening for TS
      in specialized diabetes clinics. Whether mortality is also increased in
      individuals from the general population with diabetes and increased TS is
      unknown. RESEARCH DESIGN AND METHODS: In two Danish population studies (N =
      84,865), we examined mortality according to baseline levels of TS and
      hemochromatosis genotype (HFE) G -> A substitution at nucleotide 845 in codon 282
      (C282Y/C282Y) in individuals with diabetes (type 1, N = 118; type 2, N = 3,228;
      total, N = 3,346). RESULTS: The cumulative survival rate was reduced in
      individuals with diabetes with TS >=50% vs. <50% (log-rank; P < 0.0001), with
      median survival ages of 66 and 79 years, respectively. The hazard ratio (HR) for
      TS >=50% vs. <50% was 2.0 (95% CI 1.3-2.8; P = 0.0004) for total mortality
      overall (and similar for men and women separately); 2.6 (1.3-5.4; P = 0.008) for
      neoplasms; and 3.4 (2.0-6.0; P = 0.00002) for endocrinological causes. A stepwise
      increased risk of total mortality was observed for stepwise increasing TS (log
      rank test, P = 0.0001), with an HR for TS >=70% vs. TS <20% of 4.8 (2.0-12; P =
      0.0006). The HR for total mortality in individuals with diabetes for C282Y/C282Y
      versus wild type/wild type was 3.3 (1.04-10; P = 0.04), and for C282Y/C282Y and
      TS >=50% versus wild type/wild type and TS <50% was 6.0 (1.5-24; P = 0.01). Six
      percent of these premature deaths can possibly be avoided by early screening for
      TS or HFE genotype. CONCLUSIONS: Individuals with diabetes, ascertained in the
      general population, with increased TS or HFE genotype have a twofold to sixfold
      increased risk of premature death.

PMID- 24130349
TI  - Iron status and survival in diabetic patients with coronary artery disease.
AB  - OBJECTIVE: To investigate the impact of iron status on survival in patients with
      type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS:
      Serum ferritin, transferrin saturation (Tsat), and soluble transferrin receptor
      (sTfR) were measured in 287 patients with type 2 diabetes and stable CAD (65 +/-
      9 years of age, 78% men). RESULTS: During a mean follow-up of 45 +/- 19 months,
      there were 59 (21%) deaths and 60 (21%) cardiovascular hospitalizations. Both
      serum ferritin and sTfR strongly predicted 5-year all-cause mortality rates,
      independently of other variables (including hemoglobin, measures of renal
      function, inflammation, and neurohormonal activation). There was an exponential
      relationship between sTfR and mortality (adjusted hazard ratio [HR] per 1 log
      mg/L: 4.24 [95% CI 1.43-12.58], P = 0.01), whereas the relationship between
      ferritin and mortality was U-shaped (for the lowest and the highest quintiles vs.
      the middle quintile [reference group], respectively: adjusted HR 7.18 [95% CI
      2.03-25.46], P = 0.002, and adjusted HR 5.12 [1.48-17.73], P = 0.01). Similar
      patterns were observed for the composite outcome of all-cause mortality or
      cardiovascular hospitalization, and in these multivariable models, low Tsat was
      related to unfavorable outcome. CONCLUSIONS: Both low and high serum ferritin
      (possibly reflecting depleted and excessive iron stores, respectively) along with
      high serum sTfR (reflecting reduced metabolically available iron) identify
      patients with type 2 diabetes and CAD who have a poor prognosis.

PMID- 24130351
TI  - Vitamin C further improves the protective effect of glucagon-like peptide-1 on
      acute hypoglycemia-induced oxidative stress, inflammation, and endothelial
      dysfunction in type 1 diabetes.
AB  - OBJECTIVE: To test the hypothesis that acute hypoglycemia induces endothelial
      dysfunction and inflammation through the generation of an oxidative stress.
      Moreover, to test if the antioxidant vitamin C can further improve the protective
      effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and
      inflammation during hypoglycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS:
      A total of 20 type 1 diabetic patients underwent four experiments: a period of 2
      h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both.
      At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso
      prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a),
      interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of
      hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1,
      8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous
      infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena.
      Vitamin C was more effective. When GLP-1 and vitamin C were infused
      simultaneously, the deleterious effect of hypoglycemia was almost completely
      counterbalanced. RESULTS: At 2 h of hypoglycemia, flow-mediated vasodilation
      significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6
      significantly increased. The simultaneous infusion of GLP-1 or vitamin C
      significantly attenuated all of these phenomena. Vitamin C was more effective.
      When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of
      hypoglycemia was almost completely counterbalanced. CONCLUSIONS: This study shows
      that vitamin C infusion, during induced acute hypoglycemia, reduces the
      generation of oxidative stress and inflammation, improving endothelial
      dysfunction, in type 1 diabetes. Furthermore, the data support a protective
      effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an
      endothelial resistance to the action of GLP-1, reasonably mediated by oxidative
      stress.

PMID- 24130352
TI  - Diabetes and risk of hospitalized fall injury among older adults.
AB  - OBJECTIVE: To determine whether older adults with diabetes are at increased risk
      of an injurious fall requiring hospitalization. RESEARCH DESIGN AND METHODS: The
      longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged
      70-79 years at baseline. Hospitalizations that included ICD-9-Clinical
      Modification codes for a fall and an injury were identified. The effect of
      diabetes with and without insulin use on the rate of first fall-related injury
      hospitalization was assessed using proportional hazards models. RESULTS: At
      baseline, 719 participants had diabetes, and 117 of them were using insulin. Of
      the 293 participants who were hospitalized for a fall-related injury, 71 had
      diabetes, and 16 were using insulin. Diabetes was associated with a higher rate
      of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12
      1.95]) in models adjusted for age, race, sex, BMI, and education. In those
      participants using insulin, compared with participants without diabetes, the HR
      was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as
      fainting in the past year, standing balance score, cystatin C level, and number
      of prescription medications, accounted for some of the increased risk associated
      with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]).
      Among participants with diabetes, a history of falling, poor standing balance
      score, and A1C level >=8% were risk factors for an injurious fall requiring
      hospitalization. CONCLUSIONS: Older adults with diabetes, in particular those
      using insulin, are at greater risk of an injurious fall requiring hospitalization
      than those without diabetes. Among those with diabetes, poor glycemic control may
      increase the risk of an injurious fall.

PMID- 24130353
TI  - Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance
      and depot-specific release from adipose tissue in vivo and in vitro.
AB  - OBJECTIVE: To study expression of the recently identified adipokine dipeptidyl
      peptidase-4 (DPP4) in subcutaneous adipose tissue (SAT) and visceral adipose
      tissue (VAT) of patients with various BMIs and insulin sensitivities, as well as
      to assess circulating DPP4 in relation to obesity and insulin sensitivity.
      RESEARCH DESIGN AND METHODS: DPP4 expression was measured in SAT and VAT from 196
      subjects with a wide range of BMIs and insulin sensitivities. DPP4 release was
      measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT
      of lean and obese patients. Circulating DPP4 was measured in insulin-sensitive
      and insulin-resistant BMI-matched obese patients. RESULTS: DPP4 expression was
      positively correlated with BMI in both SAT and VAT, with VAT consistently
      displaying higher expression than SAT. Ex vivo release of DPP4 from adipose
      tissue explants was higher in VAT than in SAT in both lean and obese patients,
      with obese patients displaying higher DPP4 release than lean controls. Net
      release of DPP4 from adipose tissue was also demonstrated in vivo with greater
      release in obese subjects than in lean subjects and in women than in men. Insulin
      sensitive obese patients had significantly lower circulating DPP4 than did
      obesity-matched insulin-resistant patients. In this experiment, DPP4 positively
      correlated with the amount of VAT, adipocyte size, and adipose tissue
      inflammation. CONCLUSIONS: DPP4, a novel adipokine, has a higher release from VAT
      that is particularly pronounced in obese and insulin-resistant patients. Our data
      suggest that DPP4 may be a marker for visceral obesity, insulin resistance, and
      the metabolic syndrome.

PMID- 24130354
TI  - Dose-response effect of fruit and vegetables on insulin resistance in people at
      high risk of cardiovascular disease: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this randomized controlled trial was to investigate the
      dose-response effect of fruit and vegetable (F&V) intake on insulin resistance
      (IR) in people who are overweight and at high risk of cardiovascular disease
      (CVD). RESEARCH DESIGN AND METHODS: A total of 105 participants (mean age 56
      years) followed a 4-week washout diet (one to two portions of F&Vs per day).
      Ninety-two participants completed the washout and were randomized to receive one
      to two, four, or seven portions of F&Vs per day for 12 weeks. IR was assessed at
      the start and end of this 12-week period by the two-step euglycemic
      hyperinsulinemic clamp. Compliance was monitored using a combination of 4-day
      food diaries and plasma biomarkers of F&V intake. RESULTS: A total of 89
      participants completed the study. Participants attained self-reported F&V intakes
      of 1.8, 3.8, and 7.0 portions per day (P < 0.001) per group. There was a
      significant linear increase in serum lutein status across the groups, indicating
      good compliance (P < 0.001), and body weight was maintained (P = 0.77). No
      significant difference was found between groups in terms of a change in measures
      of whole-body, peripheral, or hepatic IR or adiponectin multimers. CONCLUSIONS:
      Increased consumption of F&Vs, as advocated in public-health advice, has no
      effect on IR in overweight individuals who are at high risk of CVD when body
      weight is maintained. Recent evidence from systematic reviews indicates that
      particular classes or types of F&Vs may have particular antidiabetic properties;
      hence, it is possible that benefits may only be observed in response to a more
      specific fruit or vegetable intervention.

PMID- 24130350
TI  - Effectiveness of early intensive therapy on beta-cell preservation in type 1
      diabetes.
AB  - OBJECTIVE: To assess effectiveness of inpatient hybrid closed-loop control (HCLC)
      followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7
      days of diagnosis of type 1 diabetes on the preservation of beta-cell function at
      1 year. RESEARCH DESIGN AND METHODS: Sixty-eight individuals (mean age 13.3 +/-
      5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP
      therapy (intensive group; N = 48) or to the usual-care group treated with
      multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C
      peptide concentrations during mixed-meal tolerance tests at 12 months. RESULTS:
      Intensive-group participants initiated HCLC a median of 6 days after diagnosis
      for a median duration of 71.3 h, during which median participant mean glucose
      concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During
      outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at
      12 months, only 33% of intensive participants averaged sensor use >=6 days/week.
      In the usual-care group, insulin pump and CGM use were initiated prior to 12
      months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in
      both groups throughout the study. At 12 months, the geometric mean (95% CI) of C
      peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group
      and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven
      (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide
      concentration >=0.2 pmol/mL (P = 0.30). CONCLUSIONS: In new-onset type 1
      diabetes, HCLC followed by SAP therapy did not provide benefit in preserving beta
      cell function compared with current standards of care.

PMID- 24130355
TI  - Restoration of self-awareness of hypoglycemia in adults with long-standing type 1
      diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the
      HypoCOMPaSS trial.
AB  - OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective
      counterregulation significantly increase severe hypoglycemia risk in type 1
      diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a
      treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH
      (Gold score >=4) participating in the U.K.-based multicenter HypoCOMPaSS
      randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with
      T1D and IAH (mean +/- SD age 50 +/- 9 years, T1D duration 35 +/- 10 years, HbA1c
      8.1 +/- 1.0% [65 +/- 10.9 mmol/mol]) underwent stepped hyperinsulinemic
      hypoglycemic clamp studies before and after a 6-month intervention. The
      intervention comprised the HypoCOMPaSS education tool in all and randomized
      allocation, in a 2 * 2 factorial study design, to multiple daily insulin analog
      injections or continuous subcutaneous insulin infusion therapy and conventional
      glucose monitoring or real-time continuous glucose monitoring. Symptoms,
      cognitive function, and counterregulatory hormones were measured at each glucose
      plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with
      subjects kept blinded to their actual glucose value throughout clamp studies.
      RESULTS: After intervention, glucose concentrations at which subjects first felt
      hypoglycemic increased (mean +/- SE from 2.6 +/- 0.1 to 3.1 +/- 0.2 mmol/L, P =
      0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher
      (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780]
      vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [
      771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive
      function measured by four-choice reaction time was unchanged, while the color
      word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long
      standing T1D, IAH and defective counterregulation may be improved by a clinical
      strategy aimed at hypoglycemia avoidance.

PMID- 24130356
TI  - Cerebral blood flow and glucose metabolism in appetite-related brain regions in
      type 1 diabetic patients after treatment with insulin detemir and NPH insulin: a
      randomized controlled crossover trial.
AB  - OBJECTIVE: To test the hypothesis that insulin detemir, which is associated with
      less weight gain than other basal insulin formulations, exerts its weight
      modulating effects by acting on brain regions involved in appetite regulation, as
      represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism
      (CMRglu). RESEARCH DESIGN AND METHODS: Twenty-eight male type 1 diabetic patients
      (age 36.9 +/- 9.7 years, BMI 24.9 +/- 2.7 kg/m(2), A1C 7.5 +/- 0.6%) successfully
      completed a randomized crossover study, consisting of two periods of 12-week
      treatment with either insulin detemir or NPH insulin, both in combination with
      prandial insulin aspart. After each treatment period, patients underwent positron
      emission tomography scans to measure regional CBF and CMRglu. RESULTS: After 12
      weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were
      similar between treatments. Insulin detemir resulted in body weight loss, whereas
      NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02).
      After treatment with insulin detemir relative to NPH insulin, CBF was higher in
      brain regions involved in appetite regulation, whereas no significant difference
      in CMRglu was observed. CONCLUSIONS: Treatment with insulin detemir versus NPH
      insulin resulted in weight loss, paralleled by increased CBF in appetite-related
      brain regions in the resting state, in men with well-controlled type 1 diabetes.
      These findings lend support to the hypothesis that a differential effect on the
      brain may contribute to the consistently observed weight-sparing effect of
      insulin detemir.

PMID- 24130357
TI  - Effect of custom-made footwear on foot ulcer recurrence in diabetes: a
      multicenter randomized controlled trial.
AB  - OBJECTIVE: Custom-made footwear is the treatment of choice to prevent foot ulcer
      recurrence in diabetes. This footwear primarily aims to offload plantar regions
      at high ulcer risk. However, ulcer recurrence rates are high. We assessed the
      effect of offloading-improved custom-made footwear and the role of footwear
      adherence on plantar foot ulcer recurrence. RESEARCH DESIGN AND METHODS: We
      randomly assigned 171 neuropathic diabetic patients with a recently healed
      plantar foot ulcer to custom-made footwear with improved and subsequently
      preserved offloading (~20% peak pressure relief by modifying the footwear) or to
      usual care (i.e., nonimproved custom-made footwear). Primary outcome was plantar
      foot ulcer recurrence in 18 months. Secondary outcome was ulcer recurrence in
      patients with an objectively measured adherence of >=80% of steps taken. RESULTS:
      On the basis of intention-to-treat, 33 of 85 patients (38.8%) with improved
      footwear and 38 of 86 patients (44.2%) with usual care had a recurrent ulcer
      (relative risk -11%, odds ratio 0.80 [95% CI 0.44-1.47], P = 0.48). Ulcer-free
      survival curves were not significantly different between groups (P = 0.40). In
      the 79 patients (46% of total group) with high adherence, 9 of 35 (25.7%) with
      improved footwear and 21 of 44 (47.8%) with usual care had a recurrent ulcer
      (relative risk -46%, odds ratio 0.38 [0.15-0.99], P = 0.045). CONCLUSIONS:
      Offloading-improved custom-made footwear does not significantly reduce the
      incidence of plantar foot ulcer recurrence in diabetes compared with custom-made
      footwear that does not undergo such improvement, unless it is worn as
      recommended.

PMID- 24130358
TI  - Targeting inflammation using salsalate in patients with type 2 diabetes: effects
      on flow-mediated dilation (TINSAL-FMD).
AB  - OBJECTIVE: To test whether inhibiting inflammation with salsalate improves
      endothelial function in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND
      METHODS: We conducted an ancillary study to the National Institutes of Health
      sponsored, multicenter, randomized, double-masked, placebo-controlled trial
      evaluating the safety and efficacy of salsalate in targeting inflammation to
      improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent
      dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD)
      of the brachial artery were assessed at baseline and 3 and 6 months following
      randomization to either salsalate 3.5 g/day or placebo. The primary end point was
      change in FMD at 6 months. RESULTS: A total of 88 participants were enrolled in
      the study, and data after randomization were available for 75. Patients in the
      treatment and control groups had similar ages (56 years), BMI (33 kg/m(2)), sex
      (64% male), ethnicity, current treatment, and baseline HbA1c (7.7% [61
      mmol/mol]). In patients treated with salsalate versus placebo, HbA1c was reduced
      by 0.46% (5.0 mmol/mol; P < 0.001), fasting glucose by 16.1 mg/dL (P < 0.001),
      and white blood cell count by 430 cells/uL (P < 0.02). There was no difference in
      the mean change in either FMD (0.70% [95% CI -0.86 to 2.25%]; P = 0.38) or NMD (
      0.59% [95% CI -2.70 to 1.51%]; P = 0.57) between the groups treated with
      salsalate and placebo at 6 months. Total and LDL cholesterol were 11 and 16 mg/dL
      higher, respectively, and urinary albumin was 2.0 ug/mg creatinine higher in the
      patients treated with salsalate compared with those treated with placebo (all P <
      0.009). CONCLUSIONS: Salsalate does not change FMD in peripheral conduit arteries
      in patients with T2D despite lowering HbA1c. This finding suggests that salsalate
      does not have an effect on vascular inflammation, inflammation does not cause
      endothelial dysfunction in T2D, or confounding effects of salsalate mitigate
      favorable effects on endothelial function.

PMID- 24130359
TI  - Body composition is the main determinant for the difference in type 2 diabetes
      pathophysiology between Japanese and Caucasians.
AB  - OBJECTIVE This cross-sectional clinical study compared the pathophysiology of
      type 2 diabetes in Japanese and Caucasians and investigated the role of
      demographic, genetic, and lifestyle-related risk factors for insulin resistance
      and beta-cell response. RESEARCH DESIGN AND METHODS A total of 120 Japanese and
      150 Caucasians were enrolled to obtain comparable distributions of high/low BMI
      values across glucose tolerance states (normal glucose tolerance, impaired
      glucose tolerance, and type 2 diabetes), which were assessed by oral glucose
      tolerance tests. BMI in the two cohorts was distributed around the two regional
      cutoff values for obesity. RESULTS Insulin sensitivity was higher in Japanese
      compared with Caucasians, as indicated by the homeostatic model assessment of
      insulin resistance and Matsuda indices, whereas beta-cell response was higher in
      Caucasians, as measured by homeostatic model assessment of beta-cell function,
      the insulinogenic indices, and insulin secretion ratios. Disposition indices were
      similar for Japanese and Caucasians at all glucose tolerance states, indicating
      similar beta-cell response relative to the degree of insulin resistance. The main
      determinants for differences in metabolic indices were measures of body
      composition, such as BMI and distribution of adipose tissue. Differences in beta
      cell response between Japanese and Caucasians were not statistically significant
      following adjustment by differences in BMI. CONCLUSIONS Our study showed similar
      disposition indices in Japanese and Caucasians and that the major part of the
      differences in insulin sensitivity and beta-cell response between Japanese and
      Caucasians can be explained by differences in body composition. 

PMID- 24130360
TI  - Ideal cardiovascular health and the prevalence and progression of coronary artery
      calcification in adults with and without type 1 diabetes.
AB  - OBJECTIVE: In 2010, the American Heart Association defined seven metrics
      (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and
      fasting plasma glucose) for ideal cardiovascular health (ICH). Subsequent studies
      have shown that the prevalence of achieving these metrics is very low in the
      general population. Adults with type 1 diabetes are at increased risk of
      cardiovascular disease (CVD), but no studies to date have been published on the
      prevalence of ICH in this population. RESEARCH DESIGN AND METHODS: Data for this
      analysis were collected as part of the prospective Coronary Artery Calcification
      in Type 1 Diabetes study. This analysis involved 546 subjects with type 1
      diabetes and 631 subjects without diabetes who had complete information for
      calculating the ICH metrics. RESULTS: Overall, the prevalence of ICH was low in
      this population, with none meeting the ideal criteria for all seven metrics. The
      prevalence of ideal physical activity (10.0%) and diet (1.1%) were particularly
      low. ICH was significantly associated with both decreased prevalence (odds ratio
      [OR] 0.70; 95% CI 0.62-0.80) and progression (OR 0.77; 95% CI 0.66-0.90) of
      coronary artery calcification (CAC). CONCLUSIONS: ICH is significantly associated
      with decreased prevalence and progression of CAC; however, prevalence of ICH
      metrics was low in adults both with and without type 1 diabetes. Efforts to
      increase the prevalence of ICH could have a significant impact on reducing the
      burden of CVD.

PMID- 24130361
TI  - Peripartum management of glycemia in women with type 1 diabetes.
AB  - OBJECTIVE: We aimed to 1) describe the peripartum management of type 1 diabetes
      at an Australian teaching hospital and 2) discuss factors influencing the
      apparent transient insulin independence postpartum. RESEARCH DESIGN AND METHODS:
      We conducted a retrospective review of women with type 1 diabetes delivering
      singleton pregnancies from 2005 to 2010. Information was collected regarding
      demographics, medical history, peripartum management and outcome, and breast
      feeding. To detect a difference in time to first postpartum blood glucose level
      (BGL) >8 mmol/L between women with an early (<4 h) and late (>12 h) requirement
      for insulin postpartum, with a power of 80% and a type 1 error of 0.05, at least
      24 patients were required. RESULTS: An intravenous insulin infusion was commenced
      in almost 95% of women. Univariate analysis showed that increased BMI at term,
      lower creatinine at term, longer duration from last dose of long- or intermediate
      acting insulin, and discontinuation of an insulin infusion postpartum were
      associated with a shorter time to first requirement of insulin postpartum (P =
      0.005, 0.026, 0.026, and <0.001, respectively). There was a correlation between
      higher doses of insulin commenced postpartum and number of out-of-range BGLs
      (r[36] = 0.358, P = 0.030) and hypoglycemia (r[36] = 0.434, P = 0.007). Almost
      60% had at least one BGL <3.5 mmol/L between delivery and discharge. CONCLUSIONS:
      Changes in the pharmacodynamic profile of insulin may contribute to the transient
      insulin independence sometimes observed postpartum in type 1 diabetes. A dose of
      50-60% of the prepregnancy insulin requirement resulted in the lowest rate of
      hypoglycemia and glucose excursions. These results require validation in a
      larger, prospective study.

PMID- 24130362
TI  - A 10-s sprint performed after moderate-intensity exercise neither increases nor
      decreases the glucose requirement to prevent late-onset hypoglycemia in
      individuals with type 1 diabetes.
AB  - OBJECTIVE: To determine whether performing a 10-s sprint after moderate-intensity
      exercise increases the amount of carbohydrate required to maintain euglycemia and
      prevent late-onset postexercise hypoglycemia relative to moderate-intensity
      exercise alone. RESEARCH DESIGN AND METHODS: Seven individuals with type 1
      diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of
      moderate-intensity exercise on two separate occasions followed by either a 10-s
      maximal sprint effort or no sprint. During the following 8 h, glucose infusion
      rate to maintain euglycemia and rates of glucose appearance and disappearance
      were measured continuously. RESULTS: In response to exercise and throughout the 8
      h recovery period, there were no differences in glucose infusion rate, blood
      glucose levels, plasma insulin concentrations, and rates of glucose appearance
      and disappearance between the two experimental conditions (P > 0.05).
      CONCLUSIONS: A 10-s sprint performed after 30 min of moderate-intensity exercise
      does not affect the amount of carbohydrate required to maintain euglycemia
      postexercise in individuals with type 1 diabetes.

PMID- 24130364
TI  - Cardiometabolic risk is associated with atherosclerotic burden and prognosis:
      results from the partners coronary computed tomography angiography registry.
AB  - OBJECTIVE: Our purpose was to evaluate coronary artery disease (CAD) prevalence
      and prognosis according to cardiometabolic (CM) risk. RESEARCH DESIGN AND
      METHODS: Registry of all patients without prior CAD referred for coronary
      computed tomography angiography (CCTA). Patients were stratified by groups of
      increasing CM risk factors (hypertension, low HDL, hypertriglyceridemia, obesity,
      and dysglycemia) as follows: patients without type 2 diabetes mellitus (T2DM)
      with fewer than three or with three or more CM risk factors, patients with T2DM
      not requiring insulin, or those with T2DM requiring insulin. Patients were
      followed for a primary end point of major adverse cardiovascular events (MACE)
      composed of unstable angina, late coronary revascularization, myocardial
      infarction (MI), and cardiovascular mortality. RESULTS: Among 1,118 patients
      (mean age 57 +/- 13 years) followed for a mean 3.1 years, there were 21 (1.9%)
      cardiovascular deaths and 13 (1.2%) MIs. There was a stepwise increase in the
      prevalence of obstructive CAD with increasing CM risk, from 15% in those without
      diabetes and fewer than three CM risk factors to as high as 46% in patients with
      T2DM requiring insulin (P < 0.001). Insulin exposure was associated with the
      highest adjusted hazard of MACE (hazard ratio 3.29 [95% CI 1.28-8.45], P = 0.01),
      whereas both T2DM without insulin (1.35, P = 0.3) and three or more CM risk
      factors without T2DM (1.48, P = 0.3) were associated with a similar rate of MACE.
      CONCLUSIONS: Patients without diabetes who have multiple metabolic risk factors
      have a similar prognosis and burden of CAD as those with T2DM not requiring
      insulin. Among patients with diabetes, the need for insulin therapy is associated
      with greater burden of CAD as well as worse prognosis.

PMID- 24130365
TI  - HbA1c and coronary heart disease risk among diabetic patients.
AB  - OBJECTIVE: Clinical trials to date have not provided definitive evidence
      regarding the effects of glucose lowering with coronary heart disease (CHD) risk
      among diabetic patients. RESEARCH DESIGN AND METHODS: We prospectively
      investigated the association of HbA1c at baseline and during follow-up with CHD
      risk among 17,510 African American and 12,592 white patients with type 2
      diabetes. RESULTS: During a mean follow-up of 6.0 years, 7,258 incident CHD cases
      were identified. The multivariable-adjusted hazard ratios of CHD associated with
      different levels of HbA1c at baseline (<6.0 [reference group], 6.0-6.9, 7.0-7.9,
      8.0-8.9, 9.0-9.9, 10.0-10.9, and >=11.0%) were 1.00, 1.07 (95% CI 0.97-1.18),
      1.16 (1.04-1.31), 1.15 (1.01-1.32), 1.26 (1.09-1.45), 1.27 (1.09-1.48), and 1.24
      (1.10-1.40) (P trend = 0.002) for African Americans and 1.00, 1.04 (0.94-1.14),
      1.15 (1.03-1.28), 1.29 (1.13-1.46), 1.41 (1.22-1.62), 1.34 (1.14-1.57), and 1.44
      (1.26-1.65) (P trend <0.001) for white patients, respectively. The graded
      association of HbA1c during follow-up with CHD risk was observed among both
      African American and white diabetic patients (all P trend <0.001). Each one
      percentage increase of HbA1c was associated with a greater increase in CHD risk
      in white versus African American diabetic patients. When stratified by sex, age,
      smoking status, use of glucose-lowering agents, and income, this graded
      association of HbA1c with CHD was still present. CONCLUSIONS: The current study
      in a low-income population suggests a graded positive association between HbA1c
      at baseline and during follow-up with the risk of CHD among both African American
      and white diabetic patients with low socioeconomic status.

PMID- 24130366
TI  - Islet-specific T-cell responses and proinflammatory monocytes define subtypes of
      autoantibody-negative ketosis-prone diabetes.
AB  - OBJECTIVE: Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis
      (DKA) in patients lacking typical features of type 1 diabetes. A validated
      classification scheme for KPD includes two autoantibody-negative ("A-")
      phenotypic forms: "A-beta-" (lean, early onset, lacking beta-cell functional
      reserve) and "A-beta+" (obese, late onset, with substantial beta-cell functional
      reserve after the index episode of DKA). Recent longitudinal analysis of a large
      KPD cohort revealed that the A-beta+ phenotype includes two distinct subtypes
      distinguished by the index DKA episode having a defined precipitant ("provoked,"
      with progressive beta-cell function loss over time) or no precipitant
      ("unprovoked," with sustained beta-cell functional reserve). These three A- KPD
      subtypes are characterized by absence of humoral islet autoimmune markers, but a
      role for cellular islet autoimmunity is unknown. RESEARCH DESIGN AND METHODS:
      Islet-specific T-cell responses and the percentage of proinflammatory
      (CD14+CD16+) blood monocytes were measured in A-beta- (n = 7), provoked A-beta+
      (n = 15), and unprovoked A-beta+ (n = 13) KPD patients. Genotyping was performed
      for type 1 diabetes-associated HLA class II alleles. RESULTS: Provoked A-beta+
      and A-beta- KPD patients manifested stronger islet-specific T-cell responses (P <
      0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01)
      than unprovoked A-beta+ KPD patients. A significant relationship between type 1
      diabetes HLA class II protective alleles and negative T-cell responses was
      observed. CONCLUSIONS: Provoked A-beta+ KPD and A-beta- KPD are associated with a
      high frequency of cellular islet autoimmunity and proinflammatory monocyte
      populations. In contrast, unprovoked A-beta+ KPD lacks both humoral and cellular
      islet autoimmunity.

PMID- 24130363
TI  - Influence of apolipoproteins on the association between lipids and insulin
      sensitivity: a cross-sectional analysis of the RISC Study.
AB  - OBJECTIVE: We evaluated whether the association of insulin sensitivity with HDL
      cholesterol (HDL) and triglycerides is influenced by major plasma
      apolipoproteins, as suggested by recent experimental evidence. RESEARCH DESIGN
      AND METHODS: This study included a cross-sectional analysis of the RISC Study, a
      multicenter European clinical investigation in 1,017 healthy volunteers balanced
      in sex (women 54%) and age strata (range 30-60 years). Insulin sensitivity (M/I
      in umol ? min(-1) ? kgFFM(-1) ? nM(-1)) was measured by the clamp technique and
      apolipoproteins (ApoB, -C3, -A1, and -E) by Multiplex Technology. RESULTS: The
      center-, sex-, and age-adjusted standardized regression coefficients (STDbeta)
      with M/I were similar for HDL and triglycerides (+19.9 +/- 1.9 vs. -20.0 +/- 2.0,
      P < 0.0001). Further adjustment for triglycerides (or HDL), BMI, and adiponectin
      (or nonesterified fatty acid) attenuated the strength of the association of M/I
      with both HDL (STDbeta +6.4 +/- 2.3, P < 0.01) and triglycerides (-9.5 +/- 2.1, P
      < 0.001). Neither ApoA1 nor ApoE and ApoB showed any association with M/I
      independent from plasma HDL cholesterol and triglycerides. ApoC3, in contrast, in
      both men and women, was positively associated with M/I independently of plasma
      lipids. A relative enrichment of plasma lipids with ApoC3 is associated with
      lower body fat percentage and lower plasma alanine amino transferase.
      CONCLUSIONS: Our results suggest that HDL cholesterol modulates insulin
      sensitivity through a mechanism that is partially mediated by BMI and adiponectin
      but not by ApoA1. Similarly, the influence of triglycerides on insulin
      sensitivity is in part mediated by BMI and is unrelated to ApoE or ApoB, but it
      is significantly modulated by ApoC3, which appears to protect from the negative
      effect of plasma lipids.

PMID- 24130367
TI  - Mortality in adult-onset autoimmune diabetes is associated with poor glycemic
      control: results from the HUNT Study.
AB  - OBJECTIVE: Knowledge on mortality in autoimmune diabetes with adult onset is
      limited. We compared mortality in adult-onset autoimmune diabetes and type 2
      diabetes, taking into account metabolic risk factors, HbA1c, lifestyle, and
      socioeconomic factors. RESEARCH DESIGN AND METHODS: Participants of the
      population-based HUNT2 Study (second survey of the Norwegian HelseUndersokelsen i
      Nord-Trondelag Study; n = 64,264) were followed up prospectively for mortality in
      the Cause of Death Registry (1995-2009). Diabetes with onset >=35 years was
      classified as autoimmune diabetes in adults if anti-GAD was positive (n = 208)
      and as type 2 diabetes if anti-GAD was negative (n = 2,425). Hazard ratios (HRs)
      of mortality from all-causes, cardiovascular disease (CVD), and ischemic heart
      disease (IHD) were calculated using the Cox proportional hazards model. RESULTS:
      Prevalence of the metabolic syndrome was lower in autoimmune diabetes than in
      type 2 diabetes (55 vs. 77%, P < 0.001). Still, autoimmune diabetes was
      associated with an increased risks of mortality from all-causes (HR 1.55 [95% CI
      1.25-1.92]), CVD (1.87 [1.40-2.48]), and IHD (2.39 [1.57-3.64]), equally high as
      in type 2 diabetes in analyses where individuals without diabetes were used as
      the reference group. The increased risk was not explained by overweight,
      lifestyle, socioeconomic position, or presence of the metabolic syndrome. Excess
      mortality was primarily observed in individuals with elevated HbA1c. CONCLUSIONS:
      Mortality in autoimmune diabetes was as high as in type 2 diabetes, despite a
      more favorable baseline metabolic risk profile. Excess risk was associated with
      poor glycemic control. The results from this study, the largest so far on
      mortality in autoimmune diabetes in adults, underscore the importance of optimal
      treatment modalities to improve survival in adult-onset autoimmune diabetes.

PMID- 24130368
TI  - Prediction of human pharmacokinetics in 2013 and beyond.
AB  - The utility of in vitro generated kinetic data to provide quantitative prediction
      of in vivo pharmacokinetic behavior is well established and forms a cornerstone
      of many research projects in drug metabolism and disposition, particularly within
      the pharmaceutical industry. This issue provides several excellent examples of
      the use of in vitro techniques for prediction of human pharmacokinetics (PK). The
      general area of in vitro-in vivo extrapolation (IVIVE) is broad and hence the
      spectrum of topics covers various aspects drug clearance and distribution and
      drug-drug interactions. Some articles were commissioned whereas others were
      identified during the reviewing process. Overall they provide a snapshot of
      activity at the end of 2013. They document that whereas the translation of some
      in vitro approaches is now established, other areas are in their infancy and need
      more development. 

PMID- 24130369
TI  - Localization of multidrug resistance-associated proteins along the blood-testis
      barrier in rat, macaque, and human testis.
AB  - The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous
      tubules, which can be beneficial for therapy not intended for the testis but may
      decrease drug efficacy for medications requiring entry to the testis. Previous
      data have shown that some of the transporters in the multidrug resistance
      associated protein (MRP) family (ABCC) are expressed in the testis. By
      determining the subcellular localization of these transporters, their physiologic
      function and effect on drug disposition may be better predicted. Using
      immunohistochemistry (IHC), we determined the site of expression of the MRP
      transporters expressed in the testis, namely, MRP1, MRP4, MRP5, and MRP8, from
      immature and mature rats, rhesus macaques, and adult humans. We determined that
      in all species MRP1 was restricted to the basolateral membrane of Sertoli cells,
      MRP5 is located in Leydig cells, and MRP8 is located in round spermatids, whereas
      MRP4 showed species-specific localization. MRP4 is expressed on the basolateral
      membrane of Sertoli cells in human and nonhuman primates, but on the apical
      membrane of Sertoli cells in immature and mature rats, representing a potential
      caution when using rat models as a means for studying drug disposition across the
      BTB. These data suggest that MRP1 may limit drug disposition into seminiferous
      tubules, as may MRP4 in human and nonhuman primates but not in rats. These data
      also suggest that MRP5 and MRP8 may not have a major impact on the penetration of
      drugs across the BTB. 

PMID- 24130370
TI  - Correlating structure and function of drug-metabolizing enzymes: progress and
      ongoing challenges.
AB  - This report summarizes a symposium sponsored by the American Society for
      Pharmacology and Experimental Therapeutics at Experimental Biology held April 20
      24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450)
      knowledge, emphasizing advances and challenges in relating structure with
      function and in applying this information to drug design. First, at least one
      structure of most major human drug-metabolizing P450 enzymes is known. However,
      the flexibility of these active sites can limit the predictive value of one
      structure for other ligands. A second limitation is our coarse-grain
      understanding of P450 interactions with membranes, other P450 enzymes, NADPH
      cytochrome P450 reductase, and cytochrome b5. Recent work has examined
      differential P450 interactions with reductase in mixed P450 systems and P450:P450
      complexes in reconstituted systems and cells, suggesting another level of
      functional control. In addition, protein nuclear magnetic resonance is a new
      approach to probe these protein/protein interactions, identifying interacting b5
      and P450 surfaces, showing that b5 and reductase binding are mutually exclusive,
      and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired
      outcome is the application of such information to control drug metabolism and/or
      design selective P450 inhibitors. A final presentation highlighted development of
      a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs
      otherwise rapidly metabolized by CYP3A4. Although understanding P450
      structure/function relationships is an ongoing challenge, translational advances
      will benefit from continued integration of existing and new biophysical
      approaches. 

PMID- 24130371
TI  - Genome-wide microsatellite characterization and marker development in the
      sequenced Brassica crop species.
AB  - Although much research has been conducted, the pattern of microsatellite
      distribution has remained ambiguous, and the development/utilization of
      microsatellite markers has still been limited/inefficient in Brassica, due to the
      lack of genome sequences. In view of this, we conducted genome-wide
      microsatellite characterization and marker development in three recently
      sequenced Brassica crops: Brassica rapa, Brassica oleracea and Brassica napus.
      The analysed microsatellite characteristics of these Brassica species were highly
      similar or almost identical, which suggests that the pattern of microsatellite
      distribution is likely conservative in Brassica. The genomic distribution of
      microsatellites was highly non-uniform and positively or negatively correlated
      with genes or transposable elements, respectively. Of the total of 115 869, 185
      662 and 356 522 simple sequence repeat (SSR) markers developed with high
      frequencies (408.2, 343.8 and 356.2 per Mb or one every 2.45, 2.91 and 2.81 kb,
      respectively), most represented new SSR markers, the majority had determined
      physical positions, and a large number were genic or putative single-locus SSR
      markers. We also constructed a comprehensive database for the newly developed SSR
      markers, which was integrated with public Brassica SSR markers and annotated
      genome components. The genome-wide SSR markers developed in this study provide a
      useful tool to extend the annotated genome resources of sequenced Brassica
      species to genetic study/breeding in different Brassica species. 

PMID- 24130372
TI  - Video-assisted thoracoscopic surgery lobectomy at 20 years: a consensus
      statement.
AB  - OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) lobectomy has been
      gradually accepted as an alternative surgical approach to open thoracotomy for
      selected patients with non-small-cell lung cancer (NSCLC) over the past 20 years.
      The aim of this project was to standardize the perioperative management of VATS
      lobectomy patients through expert consensus and to provide insightful guidance to
      clinical practice. METHODS: A panel of 55 experts on VATS lobectomy was
      identified by the Scientific Secretariat and the International Scientific
      Committee of the '20th Anniversary of VATS Lobectomy Conference-The Consensus
      Meeting'. The Delphi methodology consisting of two rounds of voting was
      implemented to facilitate the development of consensus. Results from the second
      round voting formed the basis of the current Consensus Statement. Consensus was
      defined a priori as more than 50% agreement among the panel of experts. Clinical
      practice was deemed 'recommended' if 50-74% of the experts reached agreement and
      'highly recommended' if 75% or more of the experts reached agreement. RESULTS:
      Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of
      standardized questionnaires. No statistically significant differences in the
      responses between the two rounds of questioning were identified. Consensus was
      reached on 21 controversial points, outlining the current accepted definition of
      VATS lobectomy, its indications and contraindications, perioperative clinical
      management and recommendations for training and future research directions.
      CONCLUSION: The present Consensus Statement represents a collective agreement
      among 50 international experts to establish a standardized practice of VATS
      lobectomy for the thoracic surgical community after 20 years of clinical
      experience.

PMID- 24130373
TI  - Being an editor: Process, predicaments, and privilege.

PMID- 24130374
TI  - Clinical pharmacology training in India: Status and need.
AB  - Clinical pharmacologists undertake many tasks, and this makes defining a
      curriculum challenging. This is especially so under the changing circumstances in
      developing countries, where clinical pharmacology has an expanding role. The
      clinical pharmacologist may be responsible for conducting ethical clinical
      trials, supporting the needs of the generic drug industry, providing access to
      safe, effective and affordable medicines, guiding their rational use, achieving
      millennium development goals, and supervising medicines management standards for
      hospital accreditation. Clinical pharmacologists, including those in developing
      countries, have a great opportunity to contribute to public health and the growth
      of pharmaceutical industry, but at present, less clinical research is undertaken
      and fewer clinical trials are done than might be expected. Here we review
      clinical pharmacology training in India, consider the needs of different
      professionals contributing to clinical research and medicines utilization, and
      suggest ways in which current programs can be modified and new programs started.
      The conclusions are relevant to clinical pharmacology in both the developing and
      the developed world. 

PMID- 24130375
TI  - Sexually transmitted diseases putative drug target database: a comprehensive
      database of putative drug targets of pathogens identified by comparative
      genomics.
AB  - OBJECTIVE: Sexually transmitted diseases (STD) are the serious public health
      problems and also impose a financial burden on the economy. Sexually transmitted
      infections are cured with single or multiple antibiotics. However, in many cases
      the organism showed persistence even after treatment. In the current study, the
      set of druggable targets in STD pathogens have been identified by comparative
      genomics. MATERIALS AND METHODS: The subtractive genomics scheme exploits the
      properties of non-homology, essentiality, membrane localization and metabolic
      pathway uniqueness in identifying the drug targets. To achieve the effective use
      of data and to understand properties of drug target under single canopy, an
      integrated knowledge database of drug targets in STD bacteria was created. Data
      for each drug targets include biochemical pathway, function, cellular
      localization, essentiality score and structural details. RESULTS: The proteome of
      STD pathogens yielded 44 membrane associated proteins possessing unique metabolic
      pathways when subjected to the algorithm. The database can be accessed at
      http://biomedresearchasia.org/index.html. CONCLUSION: Diverse data merged in the
      common framework of this database is expected to be valuable not only for basic
      studies in clinical bioinformatics, but also for basic studies in immunological,
      biotechnological and clinical fields.

PMID- 24130376
TI  - Antipsychotics in children and adolescents with schizophrenia: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To systematically review the efficacy and tolerability data of
      antipsychotics in children and adolescents with schizophrenia. MATERIALS AND
      METHODS: Pubmed, Google scholar and Psych Info were searched to identify studies
      published in peer-reviewed English language journals. All studies evaluating the
      efficacy of antipsychotics in children and adolescents with schizophrenia and
      having 3 or more participants were included. Of the studies identified, only
      randomized controlled trials were included in the meta-analysis. Data was
      analysed using effect size calculation as per Cohen's d. Fifty published studies
      were identified which reported use of antipsychotics in children and adolescents
      with schizophrenia. Of these, 15 randomized controlled studies were included in
      meta-analysis. RESULTS: Evidence suggests that both first generation
      antipsychotics (FGA) and second generation antipsychotics (SGAs) are better than
      placebo (effect size [ES] 2.948, confidence interval [CI] 1.368 to 4.528, sample
      size 31; and ES 0.454, CI 0.414 to 0.542, sample size 1308 respectively).
      However, FGAs seemed to be inferior to SGAs (ES -0.363, CI -0.562 to -0.163,
      sample size of 243) and clozapine is superior to all other antipsychotics (ES
      0.848, CI 0.748 to 0.948, and sample size 85) in treatment of schizophrenia in
      children and adolescents. The extrapyramidal side effects are more common with
      FGAs while metabolic adverse effects are more common with SGAs. CONCLUSION: FGAs
      and SGAs are effective in the treatment of children and adolescents with
      schizophrenia. Clozapine apparently is the most effective antipsychotic in this
      condition.

PMID- 24130377
TI  - Efficacy and safety of anti-tuberculosis drugs in HIV-positive patients: a
      prospective study.
AB  - OBJECTIVES: To assess the efficacy and safety of anti-tuberculosis drugs in HIV
      positive patients at a tertiary care teaching hospital. MATERIALS AND METHODS: As
      a part of an ongoing study of opportunistic infections (OIs) in HIV-positive
      patients, drug treatment in patients suffering from tuberculosis was assessed to
      determine its efficacy and safety. Based on prevalence data for last three years,
      a purposive sampling of study population was carried out in this observational,
      prospective, single centre study. Tuberculosis (TB) was the most common OI
      observed. The selected patients were followed up for a period of one year to
      evaluate the clinical course and outcome of OIs, and the efficacy and safety of
      drugs used was checked. RESULTS: Tuberculosis was observed in 89 out of 134
      enrolled patients. These included 79 adults and 10 children. Males (66.2%) were
      commonly affected. Extra pulmonary TB (73%) was the most common manifestation
      with abdominal TB observed in 55 (61.7%) patients. All patients were treated in
      accordance with the Revised National Tuberculosis Control Programme (RNTCP)
      guidelines as recommended by National AIDS Control Organization (NACO), India.
      Outcome of TB was assessable in 70 patients. Majority (82.8%) of the patients
      were cured, while 12 patients (17.1%) died during the course of treatment. A
      total of 149 ADRs were observed in 67 (75.2%) patients. Majority of ADRs (n =
      147) were non-serious and did not warrant a change in therapy. Discoloration of
      urine was the most common ADR observed. CONCLUSION: TB is the most common
      opportunistic infection in HIV-positive patients with abdominal TB being the most
      common manifestation. RNTCP and NACO guidelines are adhered to in these patients.
      Anti-tuberculosis drugs are well tolerated and effective in majority of the
      patients.

PMID- 24130378
TI  - Effect of ethanolic extract of leaves of Paederia foetida Linn. on acetic acid
      induced colitis in albino rats.
AB  - OBJECTIVES: To evaluate the effect of ethanolic extract of leaves of Paederia
      foetida on acetic acid induced colitis in albino rats. MATERIALS AND METHODS:
      Ethanolic extract of Paederia foetida (EEPF) was prepared by percolation method.
      Acute toxicity test was done by using Organization for Economic Cooperation and
      Development guidelines. Albino rats were divided into four groups of five animals
      each. Groups A and B received 3% gum acacia. Groups C and D received EEPF 500
      mg/kg body weight (BW) and 5-aminosalisylic acid 100 mg/kg BW respectively.
      Colitis was induced by transrectal administration of 4% acetic acid on 5(th) day.
      All animals were sacrificed after 48 h of colitis induction and distal 10 cm of
      the colon was dissected. Colon was weighed for disease activity index (DAI) and
      scored macroscopically and microscopically. Biochemical assessment of tissue
      myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) was done in
      colonic tissue homogenate and malondialdehyde (MDA) was estimated in serum.
      RESULTS: P. foetida showed significant (P < 0.05) reduction in DAI, macroscopic
      and microscopic lesion score as well as significant (P < 0.05) improvement in
      MPO, MDA, CAT, and SOD level as compared to Group B. CONCLUSIONS: The ethanolic
      extract of leaves of P. foetida showed significant amelioration of experimentally
      induced colitis, which may be attributed to its anti-inflammatory and antioxidant
      property.

PMID- 24130379
TI  - Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial
      infarction: a role for toll-like receptor 4.
AB  - OBJECTIVES: Toll-like receptor 4 (TLR4) is crucial in cardiomyocyte apoptosis
      induced by myocardial infarction (MI) and carvedilol has been reported to have
      anti-apoptotic effects. We hypothesized that the effects of this agent are in
      part mediated through TLR4 signaling pathways. MATERIALS AND METHODS: A total of
      48 rats were randomized to the following groups before surgery: sham-operated
      group (n = 8), MI group (n = 10) and three carvedilol-treatment groups (n = 30, 2
      mg/kg, 10 mg/kg and 30 mg/kg). Sham and MI groups were given vehicle and
      carvedilol groups received different dose carvedilol, by direct gastric gavage
      for 7 days. On the 4(th) day of drug or vehicle administration, MI model was
      produced by ligating the left anterior descending coronary artery. On day 3 after
      MI, apoptosis was assessed by TdT-UTP nick-end assay; the levels of expression of
      Bax, Bcl-2, TLR4 and nuclear factor-kappaB (NF-kappaB) in infarcted myocardium
      were analyzed by immunohistochemistry. RESULTS: Carvedilol ameliorated MI-induced
      apoptosis in a dose-dependent manner. In parallel, carvedilol also decreased the
      ratio of Bax to Bcl-2, the expression of TLR4 and NF-kappaB induced by MI. The
      extent of apoptosis and Bax-Bcl-2 ratio was strongly correlated with the TLR4
      levels. CONCLUSION: This study suggests that the short-term administration of
      carvedilol can significantly alleviate cardiomyocyte apoptosis in the infarcted
      myocardium probably by inhibiting the excessive expression of TLR4 and NF-kappaB
      induced by infarction.

PMID- 24130380
TI  - Antitumor and antioxidant status of Terminalia catappa against Ehrlich ascites
      carcinoma in Swiss albino mice.
AB  - OBJECTIVE: The present study was undertaken to evaluate the antitumor and
      antioxidant status of ethanol extract of Terminalia catappa leaves against
      Ehrlich ascites carcinoma (EAC) in Swiss albino mice. MATERIALS AND METHODS: The
      leaves powder was extracted with Soxhlet apparatus and subjected to hot
      continuous percolation using ethanol (95% v/v). Tumor bearing animals was treated
      with 50 and 200 mg/kg of ethanol extract. EAC induced in mice by intraperitoneal
      injection of EAC cells 1 * 10(6) cells/mice. The study was assed using life span
      of EAC-bearing hosts, hematological parameters, volume of solid tumor mass and
      status of antioxidant enzymes such as lipid peroxidation (LPO), reduced
      glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities.
      Total phenolics and flavonoids contents from the leaves extract were also
      determined. RESULTS: Total phenolics and flavonoids contents from the leaves
      extract were found 354.02 and 51.67 mg/g extract. Oral administration of ethanol
      extract of T. catappa (50 and 200 mg/kg) increased the life span (27.82% and
      60.59%), increased peritoneal cell count (8.85 +/- 0.20 and 10.37 +/- 0.26) and
      significantly decreased solid tumor mass (1.16 +/- 0.14 cm(2)) at 200 mg/kg as
      compared with EAC-tumor bearing mice (P < 0.01). Hematological profile including
      red blood cell count, white blood cell count, hemoglobin (11.91 +/- 0.47 % g) and
      protein estimation were found to be nearly normal levels in extract-treated mice
      compared with tumor bearing control mice. Treatment with T. catappa significantly
      decreased levels of LPO and GSH, and increased levels of SOD and CAT activity (P
      < 0.01). CONCLUSION: T. catappa exhibited antitumor effect by modulating LPO and
      augmenting antioxidant defense systems in EAC bearing mice. The phenolic and
      flavonoid components in this extract may be responsible for antitumor activity.

PMID- 24130381
TI  - Effect of sequential versus standard Helicobacter pylori eradication therapy on
      the associated iron deficiency anemia in children.
AB  - OBJECTIVES: Helicobacter pylori infection may be associated with low iron stores
      and iron deficiency anemia. Eradication of infection by the standard 10-day
      therapy (a proton pump inhibitor [PPI], clarithromycin and amoxicillin; each
      given orally, twice daily) is decreasing. The sequential 10-day therapy (a PPI
      and amoxicillin; each given orally twice daily for 5 days; followed by a PPI,
      clarithromycin and tinidazole; each given orally twice daily for another 5 days)
      may achieve higher eradication rates. This study was designed to investigate,
      which eradication regimen; sequential or standard; more effectively improves the
      associated iron status and iron deficiency in children. MATERIALS AND METHODS:
      Children (12-15 years) with H. pylori active infection (positive H. pylori
      immunoglobulin G and urea breath test [UBT]) were subjected to measurement of
      serum ferritin and then randomized into two groups to receive standard and
      sequential eradication therapy. Six weeks after completing therapy, UBT was
      performed to check eradication and serum ferritin was measured to estimate
      affection by therapy. Statistical Package for Social Sciences (SPSS, IBM, NY,
      USA) was used for analysis. RESULTS: H. pylori eradication rates of sequential
      versus standard therapy were non-significantly different. Serum ferritin non
      significantly differed between the two therapy groups and in the same group
      before and after treatment. CONCLUSIONS: There is no significant difference in H.
      pylori eradication rates between sequential and standard therapies in children.
      Moreover, no significant relationship was found between eradication therapy and
      serum ferritin. Further studies enrolling more markers of iron deficiency are
      required to precisely assess this relationship.

PMID- 24130382
TI  - Wound healing activity of Sida cordifolia Linn. in rats.
AB  - INTRODUCTION: The present study provides a scientific evaluation for the wound
      healing potential of ethanolic (EtOH) extract of Sida cordifolia Linn. (SCL)
      plant. MATERIALS AND METHODS: Excision, incision and burn wounds were inflicted
      upon three groups of six rats each. Group I was assigned as control (ointment
      base). Group II was treated with 10% EtOH extract ointment. Group III was treated
      with standard silver sulfadiazine (0.01%) cream. The parameters observed were
      percentage of wound contraction, epithelialization period, hydroxyproline
      content, tensile strength including histopathological studies. RESULT: It was
      noted that the effect produced by the ethanolic extract of SCL ointment showed
      significant (P < 0.01) healing in all wound models when compared with the control
      group. All parameters such as wound contraction, epithelialization period,
      hydroxyproline content, tensile strength and histopathological studies showed
      significant (P < 0.01) changes when compared with the control. CONCLUSION: The
      ethanolic extract ointment of SCL effectively stimulates wound contraction;
      increases tensile strength of excision, incision and burn wounds.

PMID- 24130383
TI  - Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation
      of arachidonic acid pathway.
AB  - OBJECTIVES: The objective of this study was to evaluate the peripheral analgesic
      effect of Piper betle leaf extract (PBE) along with establishing its putative
      mechanism of action. MATERIALS AND METHODS: Male Swiss albino mice after pre
      treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid
      i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the
      mechanism of action, the murine peritoneal exudate was incubated with PBE for 1
      h, followed by exposure to arachidonic acid (AA) and generation of reactive
      oxygen species (ROS) was measured by flow cytometry using 2',7'
      dichlorodihydrofluorescein diacetate. RESULTS: PBE in a dose dependent manner
      significantly reduced acetic acid induced writhing response in mice (P < 0.001).
      In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS,
      P < 0.01. CONCLUSIONS: The present study indicates that PBE has promising
      analgesic activity, worthy of future pharmacological consideration.

PMID- 24130384
TI  - Panaxquin quefolium diolsaponins dose-dependently inhibits the proliferation of
      vascular smooth muscle cells by downregulating proto-oncogene expression.
AB  - OBJECTIVES: Panax quinquefolium saponins (PQS) potentially prevent
      atherosclerosis in vivo. The proliferation of vascular smooth muscle cells
      (VSMCs) plays an important role in coronary heart disease and restenosis after
      percutaneous coronary intervention. Here, we investigated the potential effect of
      Panax quinquefolium diolsaponins (PQDS), a subtype of PQS, on angiotensin II
      (AngII)-induced VSMC proliferation. MATERIALS AND METHODS: Isolated rat VSMCs
      were identified by immunocytochemical analysis. Cell proliferation was determined
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The
      cell cycle and proliferation index were analyzed using flow cytometry. The
      messenger ribonucleic acid (mRNA) expression of proto-oncogenes was evaluated
      using reverse transcription polymerase chain reaction. RESULTS: Over 98% of
      cultured VSMCs were immunopositive for anti-alpha-smooth muscle actin. AngII
      promoted cell proliferation, whereas PQDS significantly suppressed VSMC growth in
      a dose-dependent manner. Moreover, PQDS suppressed AngII-induced proliferation of
      VSMCs by arresting the Gap 0/Gap 1 phase. Down-regulated mRNA expressions of
      proto-oncogenes occurred after PQDS application. CONCLUSIONS: Our study
      demonstrates that PQDS may reduce AngII-stimulated VSMC proliferation by
      suppressing the expression of proto-oncogenes. These results may provide insights
      for the development of novel traditional Chinese medicines to prevent
      atherosclerosis.

PMID- 24130386
TI  - Evaluation of poison information services provided by a new poison information
      center.
AB  - AIM: The aim of this study is to assess the nature and quality of services
      provided by poison information center established at a tertiary-care teaching
      hospital, Mysore. SETTINGS AND DESIGN: This was a prospective observational
      study. MATERIALS AND METHODS: The poison information center was officially
      established in September 2010 and began its functioning thereafter. The center is
      equipped with required resources and facility (e.g., text books, Poisindex,
      Drugdex, toll free telephone service, internet and online services) to provide
      poison information services. The poison information services provided by the
      center were recorded in documentation forms. The documentation form consists of
      numerous sections to collect information on: (a) Type of population (children,
      adult, elderly or pregnant) (b) poisoning agents (c) route of exposure (d) type
      of poisoning (intentional, accidental or environmental) (e) demographic details
      of patient (age, gender and bodyweight) (f) enquirer details (background, place
      of call and mode of request) (g) category and purpose of query and (h) details of
      provided service (information provided, mode of provision, time taken to provide
      information and references consulted). The nature and quality of poison
      information services provided was assessed using a quality assessment checklist
      developed in accordance with DSE/World Health Organization guidelines.
      STATISTICAL ANALYSIS: Chi-Square test (chi(2)). RESULTS: A total of 419 queries
      were received by the center. A majority (n = 333; 79.5%) of the queries were
      asked by the doctors to provide optimal care (n = 400; 95.5%). Most of the
      queries were received during ward rounds (n = 201; 48.0%), followed by direct
      access (n = 147; 35.1%). The poison information services were predominantly
      provided through verbal communication (n = 352; 84.0%). Upon receipt of queries,
      the required service was provided immediately (n = 103; 24.6%) or within 10-20
      min (n = 296; 70.6%). The queries were mainly related to intentional poisoning (n
      = 258; 64.5%), followed by accidental poisoning (n = 142; 35.5%). The most common
      poisoning agents were medicines (n = 124; 31.0%). The service provided was graded
      as "Excellent" for the majority of queries (n = 360; 86%; P < 0.001), followed by
      "Very Good" (n = 50; 12%) and "Good" (n = 9; 2%). CONCLUSION: The poison
      information center provided requested services in a skillful, efficient and
      evidence-based manner to meet the needs of the requestor. The enquiries and
      information provided is documented in a clear and systematic manner.

PMID- 24130385
TI  - An evaluation of the protective role of alpha-tocopherol on free radical induced
      hepatotoxicity and nephrotoxicity due to chromium in rats.
AB  - AIM: To avert the health problems induced by many environmental pollutants,
      available antioxidants have been evaluated. The present study was aimed to
      investigate whether alpha-tocopherol could protect the hexavalent chromium (Cr
      VI)-induced peroxidation in the liver and kidney and to explore the underlying
      mechanism of the same. MATERIALS AND METHODS: A total of 24 Wistar adult female
      rats were equally divided into four groups. Group 1 served as control while
      Groups 2 and 3 were administered K2Cr2O7(10 mg/kg b.wt. s.c. single dose). In
      addition to (Cr VI), Group 3 also received alpha-tocopherol (125 mg/kg, daily) by
      oral gavage for 14 days. Group 4 was maintained as alpha-tocopherol control (dose
      as above). At the end of 14 days, blood samples were drawn for hematology.
      Subsequently, all the rats were sacrificed to collect liver and kidney samples
      for assay of tissue peroxidation markers, antioxidant markers and functional
      markers and histopathology. RESULTS: Administration of chromium (Cr VI) in Group
      2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide
      dismutase and reduced glutathione along with significant (P < 0.05) increase in
      peroxidation markers such as malondialdehyde and protein carbonyls in the liver
      and kidney as compared with other groups. The functional markers in serum such as
      total protein was decreased significantly (P < 0.05), whereas other functional
      markers viz. alanine transaminase, blood urea nitrogen and creatinine were
      increased significantly (P < 0.05) in Group 2 as compared with the other groups.
      Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total
      erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total
      leukocyte count were observed in Cr VI treated Group 2 rats. Prominent
      pathological changes were observed in the liver and kidney of Group 2. Co
      treatment with alpha-tocopherol in Group 3 rats significantly (P < 0.05) reversed
      the Cr VI induced changes. The parameters in the study in Group 4 did not differ
      as compared with Group 1. CONCLUSIONS: alpha-tocopherol exhibited protective
      effect against Cr VI-induced damage to the liver and kidney by inhibition of
      lipid peroxidation owing its antioxidant activity.

PMID- 24130387
TI  - Chemoprotective potential of Coccinia indica against cyclophosphamide-induced
      toxicity.
AB  - OBJECTIVE: Although cyclophosphamide (CP), an alkylating agent, is used in the
      treatment of cancer owing to its broad-spectrum efficacy, its metabolites exhibit
      severe undesired toxicities in normal cells. The present study was aimed to
      investigate the chemoprotective potential of Coccinia indica against CP-induced
      oxidative stress, genotoxicity, and hepatotoxicity. MATERIALS AND METHODS:
      Rodents were orally pre-treated with Coccinia indica extract (200, 400, and 600
      mg/kg) for five consecutive days. On 5th day, these animals were injected with CP
      (50 mg/kg i.p) and sacrificed after 24 hrs. for the evaluation of oxidative
      stress, hepatotoxicity, micronucleus formation, and chromosomal aberrations.
      RESULTS: We found that the CP significantly increased malondialdehyde (MDA) and
      decreased catalase and glutathione (GSH) levels in brain, and it was
      significantly reversed by Coccinia indica extract (400 and 600 mg/kg). Further,
      pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly
      and dose-dependently reduced micronuclei formation and incidence of aberrant
      cells. We also found that the CP-induced increase in the serum biomarker enzymes
      like alkaline phosphatase (ALP), alkaline aminotransferase (ALT), and aspartate
      aminotransferase (AST) were significantly reduced by Coccinia indica extract.
      CONCLUSION: Thus, the present results indicate the protective effect of Coccinia
      indica extract against CP-induced oxidative stress, genotoxicity, as well as
      hepatotoxicity.

PMID- 24130388
TI  - Effects of nano and conventional zinc oxide on anxiety-like behavior in male
      rats.
AB  - OBJECTIVES: Current drug therapies for psychological disorders, such as anxiety,
      are not as effective as expected, and it has been shown that zinc supplements,
      such as zinc oxide (ZnO), can influence anxiety. ZnO nanoparticles (ZnO NPs) are
      among the most used nanomaterials produced and applied in many products.
      MATERIALS AND METHODS: This study investigated the effects of ZnO NPs in
      comparison with conventional ZnO (cZnO) on anxiety-like behaviors. Adult male
      Wistar rats were divided into groups: Control (receiving saline 0.9%), ZnO NPs
      (5, 10, 20 mg/kg), and cZnO (5, 10, 20 mg/kg). All drugs were dispersed in saline
      0.9%, and 30 minutes after intraperitoneal (i.p.) injection of drugs, elevated
      plus maze apparatus was used to evaluate anxiety. RESULTS: ZnO NPs (5 mg/kg) and
      cZnO (10 and 20 mg/kg) significantly increased the percentage of time spent in
      open arm (open arm time % OAT) compared with the control group (P < 0.05). This
      indicates the anxiolytic effect of such components; in addition, ZnO NPs (20
      mg/kg) reduced locomotor activity (P < 0.05). Serum zinc concentration increased
      by both anxiolytic dose of components (from 1.75 +/- 1.07 (mg/l) in control group
      to 5.31 +/- 0.53 (mg/l) in ZnO NPs (5 mg/kg) and 10.38 +/- 0.90 (mg/l) in cZnO
      (10 mg/kg) groups). Also, all doses increased serum pH (from 7.3 +/- 0.05 in
      control group to 8.1 +/- 0.05 in ZnO NPs (5 mg/kg) and 8.05 +/- 0.01 in cZnO (10
      mg/kg) groups and kept them constant after 24 hours. CONCLUSION: Results indicate
      that the anxiolytic effect of ZnO NPs is much higher than its conventional form,
      but the introduction of ZnO NPs, as a new drug for treatment of anxiety disorder,
      needs further investigations.

PMID- 24130389
TI  - Cardioprotective effect of ethanolic extract of Urtica parviflora Roxb. against
      isoproterenol induced myocardial infarction in rats.
AB  - OBJECTIVE: The objective of this study is to evaluate the effect of ethanolic
      extract of Urtica parviflora Roxb. in isoproterenol (ISO) induced myocardial
      infarction (MI) in rats. MATERIALS AND METHODS: U. parviflora Roxb. (350 mg/kg
      and 500 mg/kg, p.o) was administered for 15 days in rats. MI was induced with a
      single dose of ISO (200 mg/kg, s.c.) on the 14(th) and 15(th) day. At the end of
      the experimental period (i.e., on the day 16), serum and heart tissues were
      collected and total cholesterol (TC), high density lipoprotein, triglyceride and
      malondialdehyde, superoxide dismutase, catalase (CAT), reduced glutathione (GSH)
      and body weight were determined. RESULTS: Administration of ISO in control rats
      showed a significant (P < 0.001) increase serum cholesterol alanine transaminase
      (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and low
      density lipoprotein (LDL). There was a significant increase (P < 0.01) in the
      levels of heart tissues as compared with respective control groups. Rats treated
      with U. parviflora significantly (P < 0.01) decreased ALT, AST, ALP, LDL and TC.
      Moreover, there was an increased CAT and GSH levels in rat treated with U.
      parviflora Roxb. as compared with the control group. CONCLUSION: U. parviflora
      (350 and 500 mg/kg p.o.) is effective in controlling serum LDL levels and reduced
      cardiac complication in experimentally induced MI in rats.

PMID- 24130390
TI  - Histological changes in the liver of fetuses of pregnant rats following
      citalopram administration.
AB  - OBJECTIVE: Depression is a dilapidating disorder, which may occur during
      pregnancy. Citalopram is an antidepressant drug often prescribed to pregnant
      women. The purpose of the present study is to determine whether maternal
      administration of citalopram affects fetal liver histology. MATERIALS AND
      METHODS: Pregnant Wistar albino rats were treated with citalopram (10 or 20
      mg/kg/day). A control group received no treatment. Rat fetal liver samples were
      obtained on day 18 of gestation and evaluated morphologically and histologically.
      RESULTS: Statistical evaluation of data showed that there were no differences in
      liver weight and relative liver weight between control and citalopram treatment
      groups. Liver histology changes (such as increases in the number of Kupffer cells
      and lymphocytes) were seen in the fetuses of the group receiving a high dose of
      citalopram during gestation. Degeneration of hepatocytes was not seen and the
      megakaryocyte number did not change significantly in the citalopram treated
      groups. CONCLUSION: This study showed that citalopram administration during
      gestation may have some adverse effects on the phagocytic cell population in the
      fetal liver of rats.

PMID- 24130391
TI  - Pregabalin hypersensitivity in a patient treated for postherpetic neuralgia.
AB  - Drug hypersensitivity syndrome is characterized by fever, skin rash and internal
      organ involvement. It is commonly seen with aromatic group of anticonvulsants
      viz. phenytoin, carbamazepine and phenobarbitone. Here, we report a case of
      hypersensitivity reaction to pregabalin, used for treating postherpetic
      neuralgia. 

PMID- 24130392
TI  - Heart failure induced by itraconazole.
AB  - Itraconazole is a broad-spectrum antifungal agent. It rarely leads to adverse the
      cardiovascular effects, especially heart failure. We present here a case of a 60
      year-old female patient with itraconazole induced heart failure. 

PMID- 24130393
TI  - Anti B cell targeted therapy for autoimmune hemolytic anemia in an infant.
AB  - Autoimmune hemolytic anemia (AIHA) is an immune mediated destruction of
      erythrocytes, which has a good prognosis in children. It is known to have
      chronic, remitting or relapsing course, especially in infants and adolescents.
      Treatment of refractory or relapsing AIHA is a challenge as the other aim of the
      treatment is to avoid prolonged exposure to steroids or other immunosuppressants
      in small children. Rituximab is used in patients who are non-responsive to
      conventional treatment such as steroids, intravenous immunoglobulins and
      transfusion therapy. It has varying therapeutic success rate. We report a case of
      AIHA in a 4-month-old infant who had ill-sustained response to conventional
      therapy, but responded to rituximab. 

PMID- 24130394
TI  - Hypersensitivity due to ceftriaxone mimicking measles in a child.
AB  - Ceftriaxone is a commonly used antibiotic in children for various infections like
      respiratory tract infection, urinary tract infection and enteric fever.
      Hypersensitive reactions following ceftriaxone therapy are uncommon but are
      potentially life-threatening. The rash can resemble viral exanthems and may lead
      to a delay in the recognition and prompt treatment. Here we report a 7-year-old
      boy who presented with fever and rash with emphasis on recognizing ceftriaxone
      hypersensitivity and its management. 

PMID- 24130395
TI  - Ceftriaxone-induced hemolysis.
AB  - Immune hemolytic anemia is a rare adverse effect of ceftriaxone, a third
      generation cephalosporin, which is a commonly used antibiotic. We describe a 60
      years-old lady, a case of community-acquired pneumonia, who developed severe
      hemolysis after the first dose of ceftriaxone. Her hemoglobin dropped from 9.6 g
      /dl to 5.5 g /dl. However, she improved after discontinuation of the drug and
      blood transfusion. This report serves as a reminder to medical fraternity that
      life-threatening hemolysis can rarely follow administration of ceftriaxone. 

PMID- 24130396
TI  - Fluvoxamine induced oculogyric dystonia and manic switch in a patient with
      obsessive compulsive disorder.
AB  - Fluvoxamine has a similar spectrum of adverse effects as compared to other
      selective serotonin reuptake inhibitors. However, fluvoxamine induced oculogyric
      dystonia is a rare instance in clinical practice. In this report, we present a
      case of obsessive compulsive disorder that developed oculogyric dystonia during
      the course of fluvoxamine mono-therapy and subsequently had a manic switch. 

PMID- 24130397
TI  - Prescribing practices in private health facilities in Delhi (India).

PMID- 24130398
TI  - Bedaquiline: a new drug approved for treatment of multidrug-resistant
      tuberculosis.

PMID- 24130399
TI  - Exploring selective serotonergic modulation involved in the anticonvulsant effect
      of Ficus religiosa fig extract.

PMID- 24130400
TI  - The ideal zinc preparation in the management of acute diarrhea in children.

PMID- 24130401
TI  - Research ethics for young researchers.

PMID- 24130402
TI  - Experimental evaluation of analgesic and anti-inflammatory potential of Oyster
      mushroom Pleurotus florida.

PMID- 24130403
TI  - Author's reply: To PMID 23543896.

PMID- 24130404
TI  - CD 99 immunocytochemistry in solid pseudopapillary tumor of pancreas: A study on
      fine-needle aspiration cytology smears.
AB  - BACKGROUND: Solid pseudopapillary tumor of pancreas (SPTP) is a rare pancreatic
      tumor of uncertain histogenesis usually affecting young women. Though these
      tumors have characteristic cytomorphology, it is sometimes difficult to
      differentiate them from neuroendocrine tumors of the pancreas. We reviewed cases
      of SPTP to delineate the diagnostic cytological features and also observed
      utility of CD 99 (MIC 2) immunostaining to aid in the diagnosis of this tumor.
      AIMS: This study was designed to demonstrate the utility of CD 99 immunostaining
      along with cytological features for making a pre-operative diagnosis and
      delineating it from the neuroendocrine tumor of pancreas which is a close mimic.
      MATERIALS AND METHODS: Cytomorphological features of 11 cases of solid
      pseudopapillary neoplasm diagnosed by pre-operative fine-needle aspiration
      cytology (FNAC) at our institute were reviewed. Immunocytochemistry for CD 99 was
      also performed on the smears. RESULTS: All the cases had cellular smears with
      monomorphic cells lying singly, as loosely cohesive clusters as well as forming
      delicate pseudopapillae. Presence of intra and extra-cellular basement membrane
      material, background foamy macrophages and nuclear grooves were the other salient
      features. Immunocytochemistry for CD 99 could be performed on eight cases and
      demonstrated typical paranuclear dot-like positivity. CONCLUSIONS: Pre-operative
      early diagnosis of SPTP can be made by FNAC which can further be aided by CD 99
      immunocytochemistry.

PMID- 24130405
TI  - Clinical significance of benign endometrial cells found in papanicolaou tests of
      Turkish women aged 40 years and older.
AB  - BACKGROUND: Spontaneously exfoliated benign-appearing endometrial cells (BEC) on
      a Papanicolaou smear might indicate endometrial pathology in postmenopausal
      women, necessitating further investigation. A cut-off age of 40 years was
      included in the Bethesda System 2001 based on studies of clinical significance of
      endometrial cells in Pap smears in Western countries. AIMS: The purpose of this
      study was to determine the significance of age subgroup for women with a
      cytological diagnosis of BEC, regardless of menopausal status, in a retrospective
      cohort of Turkish women. MATERIALS AND METHODS: Between October 2006 and November
      2011, 41 patients with a BEC diagnosis and 64 patients with a cytological
      diagnosis of normal smear (NS) were enrolled; regardless of menopausal status,
      these women were 40 years and older and for whom follow-up endometrial biopsies
      had been performed. RESULTS: On subsequent histopathologic evaluation, no
      malignant lesion was detected in women aged 40-50 years compared to three
      endometrioid-type adenocarcinomas in women older than 50 years with cytological
      diagnosis of BEC. There was a significant difference between women older than 50
      years with cytologic diagnosis of BEC and NS in relation to premalignant lesions
      on histopathologic evaluation; however, this was not the case for women aged 40
      50 years. CONCLUSIONS: According to our study, reporting BEC for women aged
      between 40 and 50 years has minor clinical significance but is significant for
      women older than 50 years, regardless of menopausal status. Larger sample size
      would be appropriate to confirm the results of the current study.

PMID- 24130406
TI  - Plastic spatula with narrow long tip provides higher satisfactory smears for Pap
      test.
AB  - BACKGROUND: Ayre spatula for cervical smear collection is being used despite the
      suggestion that different modified spatulas provide more satisfactory sampling.
      AIMS: To see whether the cytological pickup improves with the use of long tipped
      spatula. SETTING AND DESIGN: Rurally based University Hospital; crossover study.
      MATERIALS AND METHODS: Pap smear using Ayre spatula in 500 and with plastic
      narrow long tip (Szalay) spatula in 500 clinic attending women was taken and
      analyzed. Crossover smears were taken with modified spatula in 163 and using Ayre
      spatula in 187 women after 2 weeks of initial smears. The same pathologist made
      cytological reporting for all smears and was unaware of the type of spatula used.
      RESULTS: Smears from Ayre spatula had significantly higher reports of inadequate
      smears (94 of 500 vs. 68 of 500 for Ayre and Szalay, respectively; P = 0.032) and
      it remained so even after crossover (94 of 187 vs. 70 of 163 for Ayre and Szalay,
      respectively; P = 0.2). Cellular quality appeared better with smears taken using
      Szalay spatula, but the overall abnormal smear detection rate remained similar
      with either collection tool (chi(2) = 1.5; P = 0.2). CONCLUSIONS: Proportion of
      satisfactory smears is higher when long tip plastic spatula is used for
      collection of sample.

PMID- 24130407
TI  - Role of biliary tract cytology in the evaluation of extrahepatic cholestatic
      jaundice.
AB  - BACKGROUND: Endoscopic evaluation is critical in assessing the cause of
      obstructive jaundice. Cytological techniques including bile aspiration and
      biliary brushings have become the initial diagnostic modality. AIM: The aim of
      this study is to evaluate the role of endoscopic biliary tract cytology as a
      diagnostic tool in the evaluation of extrahepatic cholestatic jaundice. MATERIALS
      AND METHODS: A total of 56 biliary tract specimens including 34 bile aspirations
      and 22 biliary brushings from 41 consecutive patients who had presented with
      obstructive jaundice and underwent endoscopic retrograde cholangiopancreatography
      (ERCP) were assessed by cytological examination. The smears prepared were
      analyzed for standard cytological features. RESULTS: Cytologic diagnosis was
      adenocarcinoma in 13 (31.7%) cases, atypical in 2 (4.9%), reactive in 3 (7.3%)
      and benign changes in 19 (46.3%) cases. 4 (9.8%) cases were non-diagnostic. Serum
      bilirubin was significantly elevated in the malignant group. Biliary stricture
      was the most common finding on ERCP (68.3%). On cytological examination, presence
      of solitary, intact atypical cells, enlarged nuclei, irregular nuclear membrane,
      coarse chromatin and nucleoli were important cytologic criteria for
      differentiating malignant from benign biliary specimens. CONCLUSIONS: Regular use
      of bile cytology and brushings during ERCP evaluation of extrahepatic cholestatic
      jaundice is invaluable in obtaining a morphologic diagnosis. A systematic
      approach, use of strict cytomorphologic criteria and inclusion of significant
      atypia as malignant diagnosis may improve the sensitivity.

PMID- 24130408
TI  - Demonstration of iron in exfoliated buccal cells of beta-thalassemia major
      patients.
AB  - BACKGROUND: Thalassemia is a genetic disorder of hemoglobin synthesis, which
      requires regular blood transfusion therapy leading to iron overload in the body
      tissues. Transfusional hemosiderosis is a major cause of morbidity and mortality
      in these patients. Reliable methods for evaluation of iron overload are either
      invasive, costly or remotely available. Therefore, a simple technique of
      monitoring iron overload is desirable. AIM: To know whether iron can be
      demonstrated in exfoliated buccal cells of beta-thalassemia major patients using
      Perls' Prussian blue method and to correlate it with serum ferritin levels.
      MATERIALS AND METHODS: Smears were obtained from buccal mucosa of 60 randomly
      selected beta-thalassemia major patients and 30 healthy subjects as controls.
      Smears were stained with Perls' Prussian blue method. Blood samples were taken
      for estimation of serum ferritin levels. STATISTICAL ANALYSIS: Chi-square, Mann
      Whitney, and Spearman Rank's Correlation tests. RESULTS: Perls' positivity was
      observed in 71.7% of thalassemic patients with a moderately positive correlation
      to serum ferritin levels. CONCLUSION: Oral exfoliative cytology can be a useful
      tool in demonstration of iron overload in thalassemic patients, however, further
      research in this field in the direction of quantification of these procedures is
      required, which can establish this non-invasive procedure as an ideal screening
      tool.

PMID- 24130409
TI  - Alteration in buccal mucosal cells due to the effect of tobacco and alcohol by
      assessing the silver-stained nucleolar organiser regions and micronuclei.
AB  - BACKGROUND: Oral habits such as alcohol consumption and tobacco chewing are
      considered to be initiators of dysplastic changes in the oral mucosa. AIM: The
      aim of this study was to determine and compare the alteration in apparently
      normal buccal mucosal cells due to effect of alcohol and tobacco by assessing
      silver-stained nucleolar organiser regions (AgNORs) and micronuclei. MATERIALS
      AND METHODS: The study comprised a total of 100 subjects which were divided into
      four groups with 25 subjects having alcohol consuming habit, 25 subjects were
      tobacco consumer, 25 were both alcohol and tobacco consumer and 25 formed control
      group who neither consumed alcohol nor tobacco. Two cytological smears were taken
      from each subject with the help of cytological brush. The smear was then wet
      fixed and stained with AgNOR and acridine orange staining technique and assessed
      for nucleolar organiser region and micronuclei count respectively. 500 cells per
      slide were counted to note the changes. RESULTS: Mann-Whitney test was applied to
      assess the variation in the number of AgNORs and micronuclei count between
      different groups. Cytological changes in each group revealed the increase in mean
      AgNORs and micronuclei count in subjects with combined alcohol and tobacco
      consumption when compared with individual groups. CONCLUSIONS: Tobacco and
      alcohol consumption produce alteration in apparently normal buccal mucosal cells,
      which may cumulatively lead to carcinomatous changes. Result of these changes may
      be used as educational tool in cessation of habits.

PMID- 24130410
TI  - Analyzing agreement patterns of intraoperative central nervous system lesion
      reporting according to type and grade.
AB  - BACKGROUND: Neuropathology centers are expected to offer a prompt and accurate
      intraoperative diagnosis regarding tumor/lesion type and grade on fresh unfixed
      tissue. Level of diagnostic accuracy according to type and grade and also, the
      experience at a new center has not been reported before. AIMS: The aim of this
      study is to review the agreement patterns according to tumor/lesion type and
      grade between intraoperative and final histopathologic diagnosis in central
      nervous system (CNS) lesion samples received by a newly established
      neuropathology center at a tertiary care neuropsychiatric hospital. MATERIALS AND
      METHODS: AGREEMENT BETWEEN INTRAOPERATIVE AND FINAL HISTOPATHOLOGIC DIAGNOSIS WAS
      CLASSIFIED AS: (I) Grade in agreement but type not in agreement; (II) grade not
      in agreement but type in agreement; (III) grade and type both not in agreement;
      (IV) grade and type both in agreement. STATISTICAL ANALYSIS: Confidence interval
      (CI) of agreements was calculated for various categories of neoplastic as well as
      non-neoplastic lesions. CI was also calculated for groups where n * p and n * (1 
      p) were more than 5, i.e., fulfilled the requirement of the central limit
      theorem. RESULTS: On retrospective analysis of 333 cases, 284 (85.3%) cases were
      categorized as neoplastic while 49 (14.7%) cases were categorized as non
      neoplastic. Among the neoplastic lesions agreement was seen in 237 (83.5%) cases
      while 47 (16.5%) cases showed disagreement. Similarly in non-neoplastic category;
      46 (93.9%) cases showed agreement while 3 (6.15%) cases showed disagreement. Of
      the non-neoplastic lesions, one case fell into the agreement category I, 2 in
      category III and 46 in IV. Among neoplastic lesions, there were 21 cases in
      agreement category I, 17 in II, 9 in III and 237 in IV. On analyzing the accuracy
      of intraoperative reporting according to tumor type, the break up was: -
      Astrocytic: 2 (I), 16 (II), 2 (III), 86 (IV); oligodendroglial: 8 (I), 1 (II);
      ependymal: 2 (III), 6 (IV); embryonal: 23 (IV); cranial and spinal nerve tumors:
      2 (II), 21 (IV); choroid plexus tumors: 4 (IV); meningeal tumors: 3 (I), 1 (III),
      49 (IV); metastatic tumors: 3 (I), 17 (IV); cysts (tumor-like conditions): 14
      (IV); neuronal and mixed neuronal glial tumors: 1 (III); malignant lymphoma: 1
      (III); sellar tumors: 17 (IV); and mixed gliomas: 5 (I). CONCLUSIONS: This study
      identifies problem areas of CNS intraoperative reporting, in a new center, with
      reference to tumor typing and grading. It may forewarn upcoming centers of
      neuropathology about the potential problem areas of intraoperative reporting.

PMID- 24130411
TI  - Immature germ cells in semen - correlation with total sperm count and sperm
      motility.
AB  - BACKGROUND: Current data regarding infertility suggests that male factor
      contributes up to 30% of the total cases of infertility. Semen analysis reveals
      the presence of spermatozoa as well as a number of non-sperm cells, presently
      being mentioned in routine semen report as "round cells" without further
      differentiating them into leucocytes or immature germ cells. AIM: The aim of this
      work was to study a simple, cost-effective, and convenient method for
      differentiating the round cells in semen into immature germ cells and leucocytes
      and correlating them with total sperm counts and motility. MATERIALS AND METHODS:
      Semen samples from 120 males, who had come for investigation for infertility,
      were collected, semen parameters recorded, and stained smears studied for
      different round cells. Statistical analysis of the data was done to correlate
      total sperm counts and sperm motility with the occurrence of immature germ cells
      and leucocytes. The average shedding of immature germ cells in different groups
      with normal and low sperm counts was compared. The clinical significance of
      "round cells" in semen and their differentiation into leucocytes and immature
      germ cells are discussed. CONCLUSIONS: Round cells in semen can be differentiated
      into immature germ cells and leucocytes using simple staining methods. The
      differential counts mentioned in a semen report give valuable and clinically
      relevant information. In this study, we observed a negative correlation between
      total count and immature germ cells, as well as sperm motility and shedding of
      immature germ cells. The latter was statistically significant with a P value
      0.000.

PMID- 24130412
TI  - Value of high-risk human papillomavirus 16 deoxyribonucleic acid testing with
      cytological entities in peri and postmenopausal women.
AB  - BACKGROUND: Genital human papillomavirus (HPV) infection is a sexually
      transmitted disease that is caused by HPV. Some types of HPV, called high-risk
      (HR) types may cause cell changes that sometimes lead to cervical cancer. HPV
      screening has been proposed for symptomatic female population; however, Pap test
      is the main stay in low resource setting. AIM: To detect HR HPV 16 positivity in
      perimenopausal and postmenopausal women and its association with cytological
      entities diagnosed on Pap smear. MATERIALS AND METHODS: Pap smears and cervical
      scrapes were collected from 230 women consisting of 120 perimenopausal women
      approaching menopause and 110 postmenopausal women with a cervix after cessation
      of menstruation and processed as per routine procedure for detection of HR-HPV 16
      deoxyribonucleic acid (DNA). Cytologically abnormal HPV 16 negative cases were
      also tested for other HR-HPV types. RESULTS: Among the perimenopausal women 12
      (10%) cases were positive for HR-HPV 16 consisting of 6 (5%) abnormal cases and
      108 (90%) were HPV 16 negative consisting of 5 (4.1%) abnormal cases. However,
      among 110 postmenopausal women 14 (12.7%) were positive for HPV 16 DNA consisting
      of 6 (5.4%) abnormal cases and 96 (87.2%) were HPV 16 negative consisting of 4
      (3.6%) abnormal cases. HPV 16 negative abnormal cases (9) were positive for low
      risk-HPV 6/11 consisting of atypical squamous cells (3) and low-grade squamous
      intraepithelial lesions-HPV (6). CONCLUSIONS: There is not much variation in HPV
      16 positive cases in peri and postmenopausal women. By combining HPV DNA testing
      with Pap smear more cases having potential for pre-cancer lesions may be
      detected; however, HPV test cannot replace the Pap smear in low resource setting.

PMID- 24130413
TI  - Fine-needle aspiration cytology of granular cell tumor: A report of two cases.
AB  - Granular cell tumors (GCTs) are uncommon soft tissue tumors, which are difficult
      to diagnose merely on clinical examination. Being an effective first-line
      investigation, the fine-needle aspiration cytology (FNAC) plays a significant
      role in its pre-operative recognition. However, as the tumor is likely to mimic
      certain other lesions, a cytopathologist needs to be aware of its characteristic
      cytomorphology. We report two cases of GCT who presented with subcutaneous
      swellings in the left lower back and the right-sided anterior abdominal wall for
      6 and 2 months, respectively. Both the patients had a clinical diagnosis of
      lipoma/neurofibroma. FNAC was done in both. In the first case a cytodiagnosis of
      xanthogranuloma was suggested and GCT in the second. Subsequent histologic
      examination of both showed features of GCT. FNAC would aid in presumptive
      diagnosis of GCT. 

PMID- 24130414
TI  - Extramedullary hematopoiesis as a 'clue' to diagnosis of hepatoblastoma on fine
      needle aspiration cytology: A report of two cases.
AB  - Extramedullary hematopoiesis (EMH) evidenced by erythropoietic cells and
      megakaryocytes is a characteristic feature of hepatoblastoma (HB). The typical
      cytomorphology, the presence of EMH and associated clinical and radiological
      findings offer a reliable diagnosis of hepatoblastoma by fine-needle aspiration
      cytology (FNAC). We describe the cytologic features of hepatoblastomas and
      discuss the differential diagnosis in two children, aged 53 days and 19 years.
      The usefulness of EMH in differentiating HB from other small round cell tumors
      and well differentiated hepatocellular carcinoma (HCC) on cytology is
      highlighted. 

PMID- 24130415
TI  - Acute lymphoblastic leukemia presenting as a breast lump: A report of two cases.
AB  - Extra-medullary leukemic infiltration of the breast by acute lymphoblastic
      leukemia (ALL) is very rare. We report two cases of ALL presenting as breast
      masses and diagnosed on fine-needle aspiration (FNA). Our first patient, a post
      partum 30-year-old female, developed bilateral breast lumps in her last trimester
      of pregnancy and complained of easy fatigability. Our second patient, a 14-year
      old girl, presented with a right-breast lump of 1-week duration. She had received
      treatment for ALL 1 year back and had been in complete remission for the last 1
      year. FNA of the breast nodules done in both the cases revealed diffuse
      infiltration by lymphoblasts. Subsequent hematological investigations confirmed
      bone marrow involvement by ALL in the first case and extra-medullary relapse in
      the second case. Fine-needle aspiration cytology (FNAC) is an easy and cost
      effective method for the early diagnosis of metastatic leukemic infiltration,
      avoiding unnecessary excisional biopsies in such cases. 

PMID- 24130416
TI  - Pure primary signet ring cell carcinoma breast: A rare cytological diagnosis.
AB  - Signet ring cell carcinoma (SRCC) of the breast is a rare tumor and it is
      classified by World Health Organization in 2003 classification under 'mucin
      producing carcinomas'. Pure form of SRCC breast is an extremely rare entity and
      very few cases have been reported in literature so far. We present a case of pure
      primary SRCC of the breast in a 70-year-old female, which was diagnosed on fine
      needle aspiration cytology. Cytological features generally show cellular smears
      with tumor cells showing eccentrically placed large, irregular nuclei showing
      indentations at places with cytoplasmic vacuoles. This case is being presented in
      view of its characteristic cytological features and its rarity. 

PMID- 24130417
TI  - Fine-needle aspiration cytology of myoepithelial carcinoma of salivary gland:
      Diagnostic challenge to cytopathologist.
AB  - Myoepithelial carcinoma (MC) is rare malignant salivary gland neoplasm and its
      cytologic features have been rarely described in the literature. Furthermore, MC
      shows varied cell types and patterns leading to the wide range of differential
      diagnosis on cytology. Histopathology and immunohistochemistry (IHC) are
      necessary to make a definite diagnosis. A 37-year-old female presented with
      painless, progressive swelling in the infra-auricular region since 2 years. Fine
      needle aspiration cytology was performed and cytological possibilities of
      cellular pleomorphic adenoma and myoepithelial cell neoplasm were rendered and
      patient was advised excision and histopathologic examination for final diagnosis
      and subtyping. Final diagnosis of MC was made on hematoxylin and eosin sections
      and IHC. MC is rare malignant salivary gland tumor showing a clinic-pathologic
      diversity. The cytological features of MC are diverse and may lack overt feature
      of malignancy. Pathologists should be aware of this entity while evaluating
      cytological smears of salivary gland mass. 

PMID- 24130418
TI  - Cytohistomorphology of subcutaneous phaeohypomycosis.
AB  - Phaeohypomycosis is a clinical syndrome caused by melanised or dematiaceous fungi
      characterized by the presence of brown mycelial structures in tissue section.
      These fungi are associated with a repertoire of the clinical manifestations that
      includes superficial and deep local infection to disseminated infection. Herein,
      we describe the clinical and fine-needle aspiration cytology and histopathologic
      features of a case of subcutaneous phaeohypomycosis. 

PMID- 24130419
TI  - Cytological diagnosis of Castleman's disease of the soft tissue.
AB  - Castleman's disease (CD), a rare benign disease is characterized by lymphoid
      hyperplasia of uncertain etiology that may present as a nodal or extranodal mass.
      We describe herein a rare case of CD occurring in the soft-tissue of right arm in
      a 55-year-old woman. The present case is instructive in the differential
      diagnosis of primary soft-tissue tumors, for which the possibility of CD should
      be considered. On clinical examination as well as gross examination, this disease
      mimics lymphomas and tuberculosis. Since cytological appearances vary depending
      on the type and extent of hyperplasia, fine needle aspiration cytology findings
      may not always be conclusive in all cases. We studied aspirates which revealed
      reactive hyperplasia with increased vascularity. Excision confirmed the
      diagnosis. 

PMID- 24130420
TI  - Pulmonary echinococcosis with Actinomycetes-like organisms mimicking malignancy:
      Diagnosed by fine needle aspiration cytology.

PMID- 24130421
TI  - Donovanosis: An incidental finding on Pap test.

PMID- 24130422
TI  - Aspiration cytology in the preoperative diagnosis of granular cell tumor of
      thyroid region in an 11-years-old female child.

PMID- 24130423
TI  - Role of cerebrospinal fluid cytology in 'carcinomatous meningitis' masquerading
      as 'tuberculoma'.

PMID- 24130424
TI  - Drug Therapy For Preventing Ventricular Arrhythmia In Brugada syndrome: Do We
      Have The Answers Yet?

PMID- 24130425
TI  - Novel Technique of Dual Chamber Pacing Through Mini-thoracotomy and Transatrial
      Endocardial Active Fixation Lead Insertion for Epicardial Pacing Lead
      Malfunction.
AB  - Epicardial pacing lead fixation is employed in patients with cavopulmonary
      anastamosis (Glenn shunts) when they need permanent pacing. Epicardial pacing in
      these patients may malfunction due to high pacing thresholds or diaphragmatic
      pacing. A novel technique of transatrial insertion of two endocardial screw-in
      pacing leads through right anterolateral minithoracotomy could achieve
      synchronous atrioventricular pacing in a patient with Ebsteins anomaly with
      symptomatic sinoatrial and atrioventricular nodal disease. 

PMID- 24130426
TI  - Coexistent Brugada Syndrome and Wolff-Parkinson-White Syndrome: What is the
      Optimal Management?
AB  - Coexistent Brugada syndrome and Wolff-Parkinson-White (WPW) syndrome is rare, and
      as such poses management challenges. The overlap of symptoms attributable to each
      condition, the timing of ventricular stimulation after accessory pathway ablation
      and the predictive value of programmed stimulation in Brugada syndrome are
      controversial. We describe a case of coexistent Brugada syndrome and WPW syndrome
      in a symptomatic young adult. We discuss our treatment approach and the existing
      literature along with the challenges in management of such cases. 

PMID- 24130427
TI  - Quinidine: an "endangered species" drug appropriate for management of electrical
      storm in brugada syndrome.
AB  - Brugada syndrome is an inherited channelopathy associated with an increased risk
      of syncope and sudden cardiac death. In rare cases it can be manifested with
      electrical storm. We report two cases of Brugada syndrome that presented with
      electrical storm and were treated successfully with oral quinidine, an
      "endangered species" drug. 

PMID- 24130428
TI  - Successful Right Ventricular Tachycardia Ablation in a Patient with Left
      Ventricular Non-compaction Cardiomyopathy.
AB  - We report a case of a 67-year old male with a recent diagnosis of left
      ventricular non-compaction (LVNC), initially presenting with symptomatic
      ventricular ectopy and runs of non-sustained ventricular tachycardia (VT). This
      ventricular arrhythmia originated in a structurally normal right ventricle (RV)
      and was successfully localized and ablated with the aid of the three-dimensional
      mapping and remote magnetic navigation. 

PMID- 24130429
TI  - Simultaneous Accessory Pathway and AV Node Mechanical Block.
AB  - We report a clinical case of a 22-year-old female referred to our institution due
      to palpitations and preexcitation. Her ECG suggested a right superior paraseptal
      accessory pathway (AP), which was localised during the electrophysiological study
      at the superior paraseptal region in close proximity to the His recordings.
      Reproducible orthodromic reciprocating tachycardia was induced by atrial pacing
      with extrastimuli. Cryo-mapping performed in the area of earliest atrial
      activation was not able to terminate the tachycardia. A second attempt, slightly
      more posterior, caused mechanical block of the AP, which rendered the tachycardia
      non-inducible. More pressure with the ablation catheter determined a Wenckebach
      type supra-hisian AV block, which was transient but reproducible. Given this
      finding no ablation was done. Simultaneous block to the AP and the
      atrioventricular node has rarely been reported using radiofrequency energy.
      However, to our knowledge this phenomenon has not been previously reported in
      large series using cryo-thermal energy. 

PMID- 24130430
TI  - Inappropriate ICD Shocks - When Monitoring Zones Do More Than Monitor.
AB  - The ventricular tachycardia (VT) monitoring zone in implantable cardioverter
      defibrillators (ICDs) is usually programmed to detect slow VTs. However, it is
      not well known whether programming this zone can affect the ICD arrhythmia
      redetection or confirmation criteria. We report two cases of inappropriate ICD
      shocks due to the programming of a slow VT monitoring zone in the same device
      model. 

PMID- 24130431
TI  - "Atrial torsades de pointes" Induced by Low-Energy Shock From Implantable
      Cardioverter Defibrillator.
AB  - A 58 year-old-patient developed an episode of polymorphic atrial tachycardia
      which looked like "atrial torsades de pointes" after a 5J shock from implantable
      cardioverter defibrillator. 

PMID- 24130432
TI  - Implementation of WHO/CDC Guidelines for Intentional Injury Death Surveillance: A
      Mixed-Methods Approach in Dar es Salaam, Tanzania.
AB  - A foundational implementation of the WHO/CDC Injury Surveillance Guidelines was
      conducted in Dar es Salaam region of the United Republic of Tanzania in 2005. The
      Guidelines were adapted to gather qualitative as well as quantitative data about
      intentional injury mortality which were collected concurrently at the Muhimbili
      National Hospital Mortuary. An interview schedule of 12 quantitative variables
      and one open-ended question, participant observation and newspaper reports were
      used. Mixed methods allowed an understanding of intentional injury mortality to
      emerge, even for those with the least amount of data, the 22% of homicides whose
      bodies were never claimed. Mixed methods made it possible to quantify intentional
      injury mortality rates, describe subpopulations with scanty data, and learn how
      to embed ongoing injury mortality surveillance into daily practice.

PMID- 24130433
TI  - Whole-body electromyostimulation as a means to impact muscle mass and abdominal
      body fat in lean, sedentary, older female adults: subanalysis of the TEST-III
      trial.
AB  - BACKGROUND: The primary aim of this study was to determine the effect of 12
      months of whole-body electromyostimulation (WB-EMS) exercise on appendicular
      muscle mass and abdominal fat mass in subjects specifically at risk for
      sarcopenia and abdominal obesity, but unable or unwilling to exercise
      conventionally. METHODS: Forty-six lean, nonsportive (<60 minutes of exercise per
      week), elderly women (aged 75 +/- 4 years) with abdominal obesity according to
      International Diabetes Federation criteria were randomly assigned to either a WB
      EMS group (n=23) which performed 18 minutes of intermittent, bipolar WB-EMS (85
      Hz) three sessions in 14 days or an "active" control group (n=23). Whole-body and
      regional body composition was assessed by dual energy X-ray absorptiometry to
      determine appendicular muscle mass, upper leg muscle mass, abdominal fat mass,
      and upper leg fat mass. Maximum strength of the leg extensors was determined
      isometrically by force plates. RESULTS: After 12 months, significant intergroup
      differences were detected for the primary end-points of appendicular muscle mass
      (0.5% +/- 2.0% for the WB-EMS group versus -0.8% +/- 2.0% for the control group,
      P=0.025) and abdominal fat mass (-1.2% +/- 5.9% for the WB-EMS group versus 2.4%
      +/- 5.8% for the control group, P=0.038). Further, upper leg lean muscle mass
      changed favorably in the WB-EMS group (0.5% +/- 2.5% versus -0.9% +/- 1.9%, in
      the control group, P=0.033), while effects for upper leg fat mass were borderline
      nonsignificant (-0.8% +/- 3.5% for the WB-EMS group versus 1.0% +/- 2.6% for the
      control group, P=0.050). With respect to functional parameters, the effects for
      leg extensor strength were again significant, with more favorable changes in the
      WB-EMS group (9.1% +/- 11.2% versus 1.0% +/- 8.1% in the control group, P=0.010).
      CONCLUSION: In summary, WB-EMS showed positive effects on the parameters of
      sarcopenia and regional fat accumulation. Further, considering the good
      acceptance of this technology by this nonsportive elderly cohort at risk for
      sarcopenia and abdominal obesity, WB-EMS may be a less off-putting alternative to
      impact appendicular muscle mass and abdominal fat mass, at least for subjects
      unwilling or unable to exercise conventionally.

PMID- 24130434
TI  - Histone deacetylase inhibitors as potential treatment for spinal muscular
      atrophy.
AB  - Histone acetylation plays an important role in regulation of transcription in
      eukaryotic cells by promoting a more relaxed chromatin structure necessary for
      transcriptional activation. Histone deacetylases (HDACs) remove acetyl groups and
      suppress gene expression. HDAC inhibitors (HDACIs) are a group of small molecules
      that promote gene transcription by chromatin remodeling and have been extensively
      studied as potential drugs for treating of spinal muscular atrophy. Various drugs
      in this class have been studied with regard to their efficacy in increasing the
      expression of survival of motor neuron (SMN) protein. In this review, we discuss
      the current literature on this topic and summarize the findings of the main
      studies in this field. 

PMID- 24130435
TI  - Replicating animal mitochondrial DNA.
AB  - The field of mitochondrial DNA (mtDNA) replication has been experiencing
      incredible progress in recent years, and yet little is certain about the
      mechanism(s) used by animal cells to replicate this plasmid-like genome. The long
      standing strand-displacement model of mammalian mtDNA replication (for which
      single-stranded DNA intermediates are a hallmark) has been intensively challenged
      by a new set of data, which suggests that replication proceeds via coupled
      leading- and lagging-strand synthesis (resembling bacterial genome replication)
      and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand
      (the so called RITOLS). The set of proteins required for mtDNA replication is
      small and includes the catalytic and accessory subunits of DNA polymerase gamma,
      the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding
      protein, and the mitochondrial RNA polymerase (which most likely functions as the
      mtDNA primase). Mutations in the genes coding for the first three proteins are
      associated with human diseases and premature aging, justifying the research
      interest in the genetic, biochemical and structural properties of the mtDNA
      replication machinery. Here we summarize these properties and discuss the current
      models of mtDNA replication in animal cells. 

PMID- 24130436
TI  - Frequency and spectrum of hemoglobinopathy mutations in a Uruguayan pediatric
      population.
AB  - Hemoglobinopathies are the most common recessive diseases worldwide but their
      prevalence in Uruguay has not been investigated. In this study, 397 unrelated
      outpatient children from the Pereira Rosell Hospital Center (CHPR), as well as 31
      selected patients with microcytic anemia and 28 beta-thalassemia carriers were
      analyzed for hemoglobinopathies by using biochemical and molecular biology
      methods. Parametric and non-parametric methods were used to compare the
      hematological indices between groups of genotypes. Of the 397 patients in the
      first group, approximately 1% (0.76% HbS and 0.25% beta-thalassemia) had a
      mutation in the HBB gene and 3.3% had beta-thalassemia. These mutations had a
      heterogeneous distribution that varied according to individual ancestry. HbS was
      found exclusively in individuals with declared African ancestry and had a carrier
      frequency of 2.2%. The frequency of alpha-thalassemia carriers in outpatients of
      European and African ancestry was 1.2% and 6.5%, respectively. In contrast, the
      frequency of alpha-thalassemia carriers in patients with microcytic anemia was
      25.8%, significantly higher (p < 0.01) than that observed in the sample as a
      whole and in Afro-descendants and Euro-descendants. Significant differences were
      observed in the hematological parameters between individuals with thalassemia
      genotypes and those with a normal genotype. These results indicate that
      hemoglobinopathies are a relevant health problem in Uruguay. 

PMID- 24130438
TI  - Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11
      Departments of Colombia.
AB  - The frequencies of four mitochondrial Native American DNA haplogroups were
      determined in 1526 unrelated individuals from 11 Departments of Colombia and
      compared to the frequencies previously obtained for Amerindian and Afro-Colombian
      populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest
      frequencies were found in Departments on the Caribbean coast and in the Pacific
      region, where the frequency of Afro-Colombians is higher, while the highest mtDNA
      Amerindian haplogroup frequencies were found in Departments that historically
      have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were
      found in all Departments, in contrast to the complete absence of haplogroup D and
      high frequencies of haplogroup A in Amerindian populations in the Caribbean
      region of Colombia. Our results indicate that all four Native American mtDNA
      haplogroups were widely distributed in Colombia at the time of the Spanish
      conquest. 

PMID- 24130437
TI  - Predicting the progress of colon cancer by DNA methylation markers of the p16
      gene in feces - Evidence from an animal model.
AB  - A new noninvasive screening tool for colorectal neoplasia detects epigenetic
      alterations exhibited by gastrointestinal tumor cells shed into stool. There is
      insufficient existing data to determine temporal associations between colorectal
      cancer (CRC) progression and aberrant DNA methylation. To evaluate the
      feasibility of using fecal DNA methylation status to determine CRC progression,
      we collected stool samples from 14 male SD rats aged six weeks, and administered
      subcutaneous injections of either 1,2-dimethylhydrazine or saline weekly. p16 DNA
      methylation statuses in tumorous and normal colon tissue, and from stool samples
      were determined using methylation-specific PCR. Additionally, p16 methylation was
      detected in stool DNA from 85.7% of the CRC rats. The earliest change in p16
      methylation status in the DMH-treated group stool samples occurred during week
      nine; repeatabilities were 57.1% in week 19 (p = 0.070) and 85.7% in week 34 (p =
      0.005). A temporal correlation was evidenced between progression of CRC and p16
      methylation status, as evidenced by DMH-induced rat feces. Using fecal DNA
      methylation status to determine colorectal tissue methylation status can reveal
      CRC progression. Our data suggests that p16 promoter methylation is a feasible
      epigenetic marker for the detection and may be useful for CRC screening. 

PMID- 24130439
TI  - Chromosome mapping of ribosomal genes and histone H4 in the genus Radacridium
      (Romaleidae).
AB  - In this study, two species of Romaleidae grasshoppers, Radacridium mariajoseae
      and R.nordestinum, were analyzed after CMA3/DA/DAPI sequential staining and
      fluorescence in situ hybridization (FISH) to determine the location of the 18S
      and 5S rDNA and histone H4 genes. Both species presented karyotypes composed of
      2n = 23, X0 with exclusively acrocentric chromosomes. CMA3 (+) blocks were
      detected after CMA3/DA/DAPI staining in only one medium size autosome bivalent
      and in the X chromosome in R. mariajoseae. On the other hand, all chromosomes,
      except the L1 bivalent, of R. nordestinum presented CMA3 (+) blocks. FISH
      analysis showed that the 18S genes are restricted to the X chromosome in R.
      mariajoseae, whereas these genes were located in the L2, S9 and S10 autosomes in
      R. nordestinum. In R. mariajoseae, the 5S rDNA sites were localized in the in L1
      and L2 bivalents and in the X chromosome. In R. nordestinum, the 5S genes were
      located in the L2, L3, M4 and M5 pairs. In both species the histone H4 genes were
      present in a medium size bivalent. Together, these data evidence a great
      variability of chromosome markers and show that the 18S and 5S ribosomal genes
      are dispersed in the Radacridium genome without a significant correlation. 

PMID- 24130440
TI  - Chromosomal diversification of diploid number, heterochromatin and rDNAs in two
      species of Phanaeus beetles (Scarabaeidae, Scarabaeinae).
AB  - The genus Phanaeus is included in the tribe Phanaeini, one of the most diverse
      tribes within the subfamily Scarabaeinae in terms of chromosomal characteristics.
      However, so far the species of this genus were not studied with differential
      cytogenetic techniques, limiting any inference of the probable mechanisms
      responsible for this diversity. In this work, several techniques were applied
      with the aim of cytogenetically characterizing two Phanaeus species. The
      karyotype found for Phanaeus (Notiophanaeus) chalcomelas was 2n = 12, neo-XY, and
      that of P. (N.) splendidulus was 2n = 20, Xyp, considered primitive for the
      family Scarabaeidae. The chromosomes of both species showed a high amount of
      constitutive heterochromatin (CH), with blocks rich in base pairs GC (CMA3 (+)).
      Moreover, in P. (N.) chalcomelas the marks revealed by C-banding and fluorochrome
      staining were different in size, showing CH variability. Sites of 18S ribosomal
      DNA (rDNA) were identified in one autosomal pair of P. (N.) chalcomelas and in
      five autosomal pairs of P. (N.) splendidulus. On the other hand, only one
      autosomal pair exhibited 5S rDNA sequences in these species. The results suggest
      that the karyotype differentiation of the Phanaeus species studied here involved
      pericentric inversions and centric fusions, as well as mechanisms related to
      amplification and dispersion of CH and rDNA sequences. 

PMID- 24130441
TI  - Karyotypic conservatism in five species of Prochilodus (Characiformes,
      Prochilodontidae) disclosed by cytogenetic markers.
AB  - The family Prochilodontidae is considered a group with well conserved chromosomes
      characterized by their number, morphology and banding patterns. Thence, our study
      aimed at accomplishing a cytogenetic analysis with conventional methods (Giemsa
      staining, silver staining of the nucleolus organizer regions-AgNOR, and C
      banding) and fluorescence in situ hybridization (FISH) with 18S and 5S ribosomal
      DNA probes in five species of the Prochilodus genus (Prochilodus argenteus,
      Prochilodus brevis, Prochilodus costatus, Prochilodus lineatus and Prochilodus
      nigricans) collected from different Brazilian hydrographic basins. The results
      revealed conservatism in chromosome number, morphology, AgNORs 18S and 5S rDNAs
      location and constitutive heterochromatin distribution patterns. The minor
      differences observed in this work, such as an Ag-NOR on a P. argenteus chromosome
      and a distinct C-banding pattern in P. lineatus, are not sufficient to question
      the conservatism described for this group. Future work using repetitive DNA
      sequences as probes for FISH will be interesting to further test the cytogenetic
      conservatism in Prochilodus. 

PMID- 24130442
TI  - Cytogenetic comparison of Podocnemis expansa and Podocnemis unifilis: A case of
      inversion and duplication involving constitutive heterochromatin.
AB  - Podocnemis expansa and P. unifilis present 2n = 28 chromosomes, a diploid number
      similar to those observed in other species of the genus. The aim of this study
      was to characterize these two species using conventional staining and
      differential CBG-, GTG and Ag-NOR banding. We analyzed specimens of P. expansa
      and P. unifilis from the state of Tocantins (Brazil), in which we found a 2n = 28
      and karyotypes differing in the morphology of the 13(th) pair, which was
      submetacentric in P. expansa and telocentric in P. unifilis. The CBG-banding
      patterns revealed a heterochromatic block in the short arm of pair 13 of P.
      expansa and an interstitial one in pair 13 of P. unifilis, suggesting a
      pericentric inversion. Pair 14 of P. unifilis showed an insterstitial band in the
      long arm that was absent in P. expansa, suggesting a duplication in this region.
      Ag-NORs were observed in the first chromosome pair of both species and was
      associated to a secondary constriction and heterochromatic blocks. 

PMID- 24130443
TI  - Intra- and interspecific chromosome polymorphisms in cultivated Cichorium L.
      species (Asteraceae).
AB  - Endive (Cichorium endivia L.) and chicory (C. intybus L.) both have 2n = 18, but
      until now, there has been no detailed karyomorphological characterization. The
      present work evaluated five accessions of each species using FISH with rDNA
      probes and fluorochrome staining with CMA and DAPI. Both species presented
      distinct banding patterns after fluorochrome staining: while endive had proximal
      CMA(++)/DAPI(-) bands in the short arms of pairs 1, 2 and 3, chicory had proximal
      CMA-positive bands in chromosomes 1 and 3 and interstitial in the short arm of
      chromosome 8. Among endive accessions, FISH procedures revealed conserved
      position and number of 5S and 45S rDNA sites (two and three pairs, respectively),
      associated with the CMA-positive bands. Notwithstanding, polymorphisms were
      detected within chicory accessions regarding the number and the distribution of
      rDNA sites in relation to the most frequent karyotype (two pairs with 45S and one
      with 5S rDNA). The karyological markers developed allowed karyotypic
      differentiation between both species, uncovering peculiarities in the number and
      position of rDNA sites, which suggest chromosome rearrangements, such as
      translocations in chicory cultivars. The interspecific and intraspecific
      polymorphisms observed emphasize the potential of karyomorphological evaluations,
      helping our understanding of the relationships and evolution of the group. 

PMID- 24130444
TI  - Characterization of Brazilian accessions of wild Arachis species of section
      Arachis (Fabaceae) using heterochromatin detection and fluorescence in situ
      hybridization (FISH).
AB  - The cytogenetic characterization of Arachis species is useful for assessing the
      genomes present in this genus, for establishing the relationship among their
      representatives and for understanding the variability in the available germplasm.
      In this study, we used fluorescence in situ hybridization (FISH) to examine the
      distribution patterns of heterochromatin and rDNA genes in 12 Brazilian
      accessions of five species of the taxonomic section Arachis. The heterochromatic
      pattern varied considerably among the species: complements with centromeric bands
      in all of the chromosomes (A. hoehnei) and complements completely devoid of
      heterochromatin (A. gregoryi, A. magna) were observed. The number of 45S rDNA
      loci ranged from two (A. gregoryi) to eight (A. glandulifera), while the number
      of 5S rDNA loci was more conserved and varied from two (in most species) to four
      (A. hoehnei). In some species one pair of 5S rDNA loci was observed adjacent to
      45S rDNA loci. The chromosomal markers revealed polymorphism in the three species
      with more than one accession (A. gregoryi, A. magna and A. valida) that were
      tested. The previous genome assignment for each of the species studied was
      confirmed, except for A. hoehnei. The intraspecific variability observed here
      suggests that an exhaustive cytogenetic and taxonomic analysis is still needed
      for some Arachis species. 

PMID- 24130445
TI  - Joint analysis of phenotypic and molecular diversity provides new insights on the
      genetic variability of the Brazilian physic nut germplasm bank.
AB  - The genetic variability of the Brazilian physic nut (Jatropha curcas) germplasm
      bank (117 accessions) was assessed using a combination of phenotypic and
      molecular data. The joint dissimilarity matrix showed moderate correlation with
      the original matrices of phenotypic and molecular data. However, the correlation
      between the phenotypic dissimilarity matrix and the genotypic dissimilarity
      matrix was low. This finding indicated that molecular markers (RAPD and SSR) did
      not adequately sample the genomic regions that were relevant for phenotypic
      differentiation of the accessions. The dissimilarity values of the joint
      dissimilarity matrix were used to measure phenotypic + molecular diversity. This
      diversity varied from 0 to 1.29 among the 117 accessions, with an average
      dissimilarity among genotypes of 0.51. Joint analysis of phenotypic and molecular
      diversity indicated that the genetic diversity of the physic nut germplasm was
      156% and 64% higher than the diversity estimated from phenotypic and molecular
      data, respectively. These results show that Jatropha genetic variability in
      Brazil is not as limited as previously thought. 

PMID- 24130446
TI  - Genetic structure and a selected core set of Brazilian soybean cultivars.
AB  - Soybean is one of the most valuable and profitable oil crop species and a
      thorough knowledge of the genetic structure of this crop is necessary for
      developing the best breeding strategies. In this study, a representative
      collection of soybean cultivars recommended for farming in all Brazilian regions
      was genotyped using 27 simple sequence repeat (SSR) loci. A total of 130 alleles
      were detected, with an average allelic number of 4.81 per locus. These alleles
      determined the core set that best represented this soybean germplasm. The
      Bayesian analysis revealed the presence of two clusters or subgroups within the
      whole collection (435 soybean cultivars) and the core set (31 entries). Cultivars
      of similar origin (ancestral) were clustered into the same groups in both
      analyses. The genetic diversity parameters, based on the SSR loci, revealed high
      similarity between the whole collection and core set. Differences between the two
      clusters detected in the core set were attributed more to the frequency of their
      ancestors than to their genetic base. In terms of ancestry, divergent groups were
      presented and a panel is shown which may foster efficient breeding programs and
      aid soybean breeders in planning reliable crossings in the development of new
      varieties. 

PMID- 24130447
TI  - Genetic structure of Argentinean hexaploid wheat germplasm.
AB  - The identification of genetically homogeneous groups of individuals is an ancient
      issue in population genetics and in the case of crops like wheat, it can be
      valuable information for breeding programs, genetic mapping and germplasm
      resources. In this work we determined the genetic structure of a set of 102
      Argentinean bread wheat (Triticum aestivum L.) elite cultivars using 38
      biochemical and molecular markers (functional, closely linked to genes and
      neutral ones) distributed throughout 18 wheat chromosomes. Genetic relationships
      among these lines were examined using model-based clustering methods. In the
      analysis three subpopulations were identified which correspond largely to the
      origin of the germplasm used by the main breeding programs in Argentina. 

PMID- 24130448
TI  - Cloning and characterization of endo-beta-1,4-glucanase genes in the common wheat
      line three pistils.
AB  - In this work, we report the cloning and characterization of endo-beta-1,4
      glucanase (EGase) genes (TaEG) in the common wheat line three pistils. Three TaEG
      homoeologous genes (TaEG-4A, TaEG-4B and TaEG-4D) were isolated and found to be
      located on chromosomes 4AL, 4BS and 4DS, respectively. The three genes showed
      high conservation of their coding nucleotide sequences and 3 untranslated region.
      The putative TaEG protein had a molecular mass of 69 kDa, a theoretical pI of
      9.39 and a transmembrane domain of 74-96 amino acids in the N-terminus that
      anchored the protein to the membrane. The genome sequences of TaEG-4A, TaEG-4B
      and TaEG-4D contained six exons and five introns. All of the introns, except for
      intron IV, varied in length and sequence composition. Phylogenetic analysis
      revealed that TaEG was most closely related to rice (Oryza sativa) OsGLU1. The
      TaEG transcript levels increased significantly during the subsidiary pistil
      primordium differentiation phase (spike size ~7-10 mm) in Chuanmai 28 TP
      (CM28TP). These data provide a basis for future research into the function of
      TaEG and offer insights into the molecular mechanism of the three pistils
      mutation in wheat. 

PMID- 24130449
TI  - Differential detection of transposable elements between Saccharum species.
AB  - Cultivars of sugarcane (Saccharum) are hybrids between species S. officinarum (x
      = 10, 2n = 8x = 80) and S. spontaneum (x = 8, 2n = 5 - 16x = 40 - 128). These
      accessions have 100 to 130 chromosomes, 80-85% of which are derived from S.
      officinarum, 10-15% from S. spontaneum, and 5-10% are possible recombinants
      between the two genomes. The aim of this study was to analyze the repetition of
      DNA sequences in S. officinarum and S. spontaneum. For this purpose, genomic DNA
      from S. officinarum was digested with restriction enzymes and the fragments
      cloned. Sixty-eight fragments, approximately 500 bp, were cloned, sequenced and
      had their identity analyzed in NCBI, and in the rice, maize, and sorghum genome
      databases using BLAST. Twelve clones containing partial transposable elements,
      one single-copy control, one DNA repetitive clone control and two genome controls
      were analyzed by DNA hybridization on membrane, using genomic probes from S.
      officinarum and S. spontaneum. The hybridization experiment revealed that six TEs
      had a similar repetitive DNA pattern in the genomes of S. officinarum and S.
      spontaneum, while six TEs were more abundant in the genome of S. officinarum. We
      concluded that the species S. officinarum and S. spontaneum have differential
      accumulation LTR retrotransposon families, suggesting distinct insertion or
      modification patterns. 

PMID- 24130450
TI  - In vivo evaluation of the antimutagenic and antigenotoxic effects of beta-glucan
      extracted from Saccharomyces cerevisiae in acute treatment with multiple doses.
AB  - Ample evidence suggests that cancer is triggered by mutagenic damage and diets or
      supplements capable of reducing such incidences can be related to the prevention
      of neoplasy development or to an improvement in life quality of patients who
      undergo chemotherapy. This research aimed to evaluate the antimutagenic and
      antigenotoxic activity of beta-glucan. We set up 8 experimental groups: control
      (Group 1), cyclophosphamide (Group 2), Groups 3-5 to assess the effect of beta
      glucan administration, and Groups 6-8 to evaluate the association between
      cyclophosphamide and beta-glucan. The intraperitonial concentrations of beta
      glucan used were 100, 150 and 200 mg/kg. Micronucleus and comet assays showed
      that within the first week of treatment beta-glucan presented a damage reduction
      rate between 100-62.04% and 94.34-59.52% for mutagenic and genotoxic damages,
      respectively. This activity decreased as the treatment was extended. During the
      sixth week of treatment antimutagenicity rates were reduced to 59.51-39.83% and
      antigenotoxicity was not effective. This leads to the conclusion that the
      efficacy of beta-glucan in preventing DNA damage is limited when treatment is
      extended, and that its use as a chemotherapeutic adjuvant need to be better
      clarified.

PMID- 24130451
TI  - Profile of micronucleus frequencies and nuclear abnormalities in different
      species of electric fishes (Gymnotiformes) from the Eastern Amazon.
AB  - The frequency of spontaneous micronucleus (MN) formation in fish species needs to
      be determined to evaluate their usefulness for genotoxic biomonitoring. The
      definition of a good bioindicator takes into account the current knowledge of its
      metabolic traits as well as other factors including its feeding behavior and
      relationship to the environment. In this study, we compared the basal frequencies
      of micronucleated erythrocytes and nuclear abnormalities (NA) among different
      species of the fish Order Gymnotiformes (Rhamphichthys marmoratus, Steatogenys
      elegans, Sternopygus macrurus, Parapteronotus hasemani, Gymnotus mamiraua,
      Gymnotus arapaima, Brachyhypopomus beebei, Brachyhypopomus n. sp. BENN) sampled
      in several localities of the Eastern Amazon. A baseline of MN and NA frequency in
      these fish was determined, enabling the identification of potentially useful
      species as models for genotoxicity studies. Only one impacted sample collected at
      a site in the River Caripetuba showed a significant number of NAs, which may be
      due to the release of wastewater by neighbouring mining industries and by the
      burnt fuel released by the small boats used by a local community. Our results may
      provide support for further studies in areas of the Eastern Amazon affected by
      mining, deforestation and other anthropogenic activities. 

PMID- 24130452
TI  - A note on the population genetic consequences of delayed larval development in
      insects.
AB  - Observations by Dobzhansky's group in the 1940s suggesting that the presence of
      recessive genotypes could account for lower larval developmental rates in
      Drosophila melanogaster were not confirmed at the time and all subsequent
      investigations on this subject focused on the analysis of ecological models based
      on competition among pre-adult individuals. However, a paper published in this
      journal in 1991 eventually confirmed the finding made by Dobzhansky and his co
      workers. In this report, we provide a theoretical analysis of the population
      genetic effects of a delay in the rate of larval development produced by such a
      genetic mechanism. 

PMID- 24130453
TI  - Proteomic profiling of liver from Elaphe taeniura, a common snake in eastern and
      southeastern Asia.
AB  - Snake liver has been implicated in the adaptation of snakes to a variety of
      habitats. However, to date, there has been no systematic analysis of snake liver
      proteins. In this study, we undertook a proteomic analysis of liver from the
      colubrid snake Elaphe taeniura using a combination of two-dimensional
      electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of
      flightmass spectrometry (MALDI-TOF MS). We also constructed a local protein
      sequence database based on transcriptome sequencing to facilitate protein
      identification. Of the 268 protein spots revealed by 2-DE 109 gave positive MS
      signals, 84 of which were identified by searching the NCBInr, Swiss-Prot and
      local databases. The other 25 protein spots could not be identified, possibly
      because their transcripts were not be stable enough to be detected by
      transcriptome sequencing. GO analysis showed that most proteins may be involved
      in binding, catalysis, cellular processes and metabolic processes. Forty-two of
      the liver proteins identified were found in other reptiles and in amphibians. The
      findings of this study provide a good reference map of snake liver proteins that
      will be useful in molecular investigations of snake physiology and adaptation. 

PMID- 24130454
TI  - Gene expression profile analysis of human intervertebral disc degeneration.
AB  - In this study, we used microarray analysis to investigate the biogenesis and
      progression of intervertebral disc degeneration. The gene expression profiles of
      37 disc tissue samples obtained from patients with herniated discs and
      degenerative disc disease collected by the National Cancer Institute Cooperative
      Tissue Network were analyzed. Differentially expressed genes between more and
      less degenerated discs were identified by significant analysis of microarray. A
      total of 555 genes were significantly overexpressed in more degenerated discs
      with a false discovery rate of < 3%. Functional annotation showed that these
      genes were significantly associated with membrane-bound vesicles, calcium ion
      binding and extracellular matrix. Protein-protein interaction analysis showed
      that these genes, including previously reported genes such as fibronectin, COL2A1
      and beta-catenin, may play key roles in disc degeneration. Unsupervised
      clustering indicated that the widely used morphology-based Thompson grading
      system was only marginally associated with the molecular classification of
      intervertebral disc degeneration. These findings indicate that detailed,
      systematic gene analysis may be a useful way of studying the biology of
      intervertebral disc degeneration. 

PMID- 24130455
TI  - Identification of candidate genes for lung cancer somatic mutation test kits.
AB  - Over the past three decades, mortality from lung cancer has sharply and
      continuously increased in China, ascending to the first cause of death among all
      types of cancer. The ability to identify the actual sequence of gene mutations
      may help doctors determine which mutations lead to precancerous lesions and which
      produce invasive carcinomas, especially using next-generation sequencing (NGS)
      technology. In this study, we analyzed the latest lung cancer data in the COSMIC
      database, in order to find genomic "hotspots" that are frequently mutated in
      human lung cancer genomes. The results revealed that the most frequently mutated
      lung cancer genes are EGFR, KRAS and TP53. In recent years, EGFR and KRAS lung
      cancer test kits have been utilized for detecting lung cancer patients, but they
      presented many disadvantages, as they proved to be of low sensitivity, labor
      intensive and time-consuming. In this study, we constructed a more complete
      catalogue of lung cancer mutation events including 145 mutated genes. With the
      genes of this list it may be feasible to develop a NGS kit for lung cancer
      mutation detection. 

PMID- 24130456
TI  - An RNA-binding complex involved in ribosome biogenesis contains a protein with
      homology to tRNA CCA-adding enzyme.
AB  - A multitude of proteins and small nucleolar RNAs transiently associate with
      eukaryotic ribosomal RNAs to direct their modification and processing and the
      assembly of ribosomal proteins. Utp22 and Rrp7, two interacting proteins with no
      recognizable domain, are components of the 90S preribosome or the small subunit
      processome that conducts early processing of 18S rRNA. Here, we determine the
      cocrystal structure of Utp22 and Rrp7 complex at 1.97 A resolution and the NMR
      structure of a C-terminal fragment of Rrp7, which is not visible in the crystal
      structure. The structure reveals that Utp22 surprisingly resembles a dimeric
      class I tRNA CCA-adding enzyme yet with degenerate active sites, raising an
      interesting evolutionary connection between tRNA and rRNA processing machineries.
      Rrp7 binds extensively to Utp22 using a deviant RNA recognition motif and an
      extended linker. Functional sites on the two proteins were identified by
      structure-based mutagenesis in yeast. We show that Rrp7 contains a flexible RNA
      binding C-terminal tail that is essential for association with preribosomes. RNA
      protein crosslinking shows that Rrp7 binds at the central domain of 18S rRNA and
      shares a neighborhood with two processing H/ACA snoRNAs snR30 and snR10.
      Depletion of snR30 prevents the stable assembly of Rrp7 into preribosomes. Our
      results provide insight into the evolutionary origin and functional context of
      Utp22 and Rrp7. 

PMID- 24130457
TI  - NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo
      during clathrin-mediated endocytosis.
AB  - AP-2 is the core-organizing element in clathrin-mediated endocytosis. During the
      formation of clathrin-coated vesicles, clathrin and endocytic accessory proteins
      interact with AP-2 in a temporally and spatially controlled manner, yet it
      remains elusive as to how these interactions are regulated. Here, we demonstrate
      that the endocytic protein NECAP 1, which binds to the alpha-ear of AP-2 through
      a C-terminal WxxF motif, uses an N-terminal PH-like domain to compete with
      clathrin for access to the AP-2 beta2-linker, revealing a means to allow AP-2
      mediated coordination of accessory protein recruitment and clathrin
      polymerization at sites of vesicle formation. Knockdown and functional rescue
      studies demonstrate that through these interactions, NECAP 1 and AP-2 cooperate
      to increase the probability of clathrin-coated vesicle formation and to control
      the number, size, and cargo content of the vesicles. Together, our data
      demonstrate that NECAP 1 modulates the AP-2 interactome and reveal a new layer of
      organizational control within the endocytic machinery. 

PMID- 24130458
TI  - Identification of a new stromal cell type involved in the regulation of inflamed
      B cell follicles.
AB  - Lymph node (LN) stromal cells provide survival signals and adhesive substrata to
      lymphocytes. During an immune response, B cell follicles enlarge, questioning how
      LN stromal cells manage these cellular demands. Herein, we used a murine fate
      mapping system to describe a new stromal cell type that resides in the T cell
      zone of resting LNs. We demonstrated that upon inflammation, B cell follicles
      progressively trespassed into the adjacent T cell zone and surrounded and
      converted these stromal cells into CXCL13 secreting cells that in return
      delineated the new boundaries of the growing follicle. Acute B cell ablation in
      inflamed LNs abolished CXCL13 secretion in these cells, while LT-beta deficiency
      in B cells drastically affected this conversion. Altogether, we reveal the
      existence of a dormant stromal cell subset that can be functionally awakened by B
      cells to delineate the transient boundaries of their expanding territories upon
      inflammation. 

PMID- 24130459
TI  - Design principles of the yeast G1/S switch.
AB  - A hallmark of the G1/S transition in budding yeast cell cycle is the proteolytic
      degradation of the B-type cyclin-Cdk stoichiometric inhibitor Sic1. Deleting SIC1
      or altering Sic1 degradation dynamics increases genomic instability. Certain key
      facts about the parts of the G1/S circuitry are established: phosphorylation of
      Sic1 on multiple sites is necessary for its destruction, and both the upstream
      kinase Cln1/2-Cdk1 and the downstream kinase Clb5/6-Cdk1 can phosphorylate Sic1
      in vitro with varied specificity, cooperativity, and processivity. However, how
      the system works as a whole is still controversial due to discrepancies between
      in vitro, in vivo, and theoretical studies. Here, by monitoring Sic1 destruction
      in real time in individual cells under various perturbations to the system, we
      provide a clear picture of how the circuitry functions as a switch in vivo. We
      show that Cln1/2-Cdk1 sets the proper timing of Sic1 destruction, but does not
      contribute to its destruction speed; thus, it acts only as a trigger. Sic1's
      inhibition target Clb5/6-Cdk1 controls the speed of Sic1 destruction through a
      double-negative feedback loop, ensuring a robust all-or-none transition for
      Clb5/6-Cdk1 activity. Furthermore, we demonstrate that the degradation of a
      single-phosphosite mutant of Sic1 is rapid and switch-like, just as the wild-type
      form. Our mathematical model confirms our understanding of the circuit and
      demonstrates that the substrate sharing between the two kinases is not a
      redundancy but a part of the design to overcome the trade-off between the timing
      and sharpness of Sic1 degradation. Our study provides direct mechanistic insight
      into the design features underlying the yeast G1/S switch. 

PMID- 24130460
TI  - Pregnancy weight gain and childhood body weight: a within-family comparison.
AB  - BACKGROUND: Excessive pregnancy weight gain is associated with obesity in the
      offspring, but this relationship may be confounded by genetic and other shared
      influences. We aimed to examine the association of pregnancy weight gain with
      body mass index (BMI) in the offspring, using a within-family design to minimize
      confounding. METHODS AND FINDINGS: In this population-based cohort study, we
      matched records of all live births in Arkansas with state-mandated data on
      childhood BMI collected in public schools (from August 18, 2003 to June 2, 2011).
      The cohort included 42,133 women who had more than one singleton pregnancy and
      their 91,045 offspring. We examined how differences in weight gain that occurred
      during two or more pregnancies for each woman predicted her children's BMI and
      odds ratio (OR) of being overweight or obese (BMI>=85th percentile) at a mean age
      of 11.9 years, using a within-family design. For every additional kg of pregnancy
      weight gain, childhood BMI increased by 0.0220 (95% CI 0.0134-0.0306, p<0.0001)
      and the OR of overweight/obesity increased by 1.007 (CI 1.003-1.012, p = 0.0008).
      Variations in pregnancy weight gain accounted for a 0.43 kg/m(2) difference in
      childhood BMI. After adjustment for birth weight, the association of pregnancy
      weight gain with childhood BMI was attenuated but remained statistically
      significant (0.0143 kg/m(2) per kg of pregnancy weight gain, CI 0.0057-0.0229, p
      = 0.0007). CONCLUSIONS: High pregnancy weight gain is associated with increased
      body weight of the offspring in childhood, and this effect is only partially
      mediated through higher birth weight. Translation of these findings to public
      health obesity prevention requires additional study. Please see later in the
      article for the Editors' Summary.

PMID- 24130461
TI  - Methodological and policy limitations of quantifying the saving of lives: a case
      study of the Global Fund's approach.
AB  - David McCoy and colleagues critique the dominance of "lives saved" models of
      assessing the impact of health programs, using The Global Fund as a case study.
      Please see later in the article for the Editors' Summary. 

PMID- 24130462
TI  - Saving lives in health: global estimates and country measurement.
AB  - Daniel Low-Beer and colleagues provide a response from The Global Fund on the
      PLOS Medicine article by David McCoy and colleagues critiquing their lives saved
      assessment models. Please see later in the article for the Editors' Summary. 

PMID- 24130463
TI  - Effect on postpartum hemorrhage of prophylactic oxytocin (10 IU) by injection by
      community health officers in Ghana: a community-based, cluster-randomized trial.
AB  - BACKGROUND: Oxytocin (10 IU) is the drug of choice for prevention of postpartum
      hemorrhage (PPH). Its use has generally been restricted to medically trained
      staff in health facilities. We assessed the effectiveness, safety, and
      feasibility of PPH prevention using oxytocin injected by peripheral health care
      providers without midwifery skills at home births. METHODS AND FINDINGS: This
      community-based, cluster-randomized trial was conducted in four rural districts
      in Ghana. We randomly allocated 54 community health officers (stratified on
      district and catchment area distance to a health facility: >=10 km versus <10 km)
      to intervention (one injection of oxytocin [10 IU] one minute after birth) and
      control (no provision of prophylactic oxytocin) arms. Births attended by a
      community health officer constituted a cluster. Our primary outcome was PPH,
      using multiple definitions; (PPH-1) blood loss >=500 mL; (PPH-2) PPH-1 plus women
      who received early treatment for PPH; and (PPH-3) PPH-2 plus any other women
      referred to hospital for postpartum bleeding. Unsafe practice is defined as
      oxytocin use before delivery of the baby. We enrolled 689 and 897 women,
      respectively, into oxytocin and control arms of the trial from April 2011 to
      November 2012. In oxytocin and control arms, respectively, PPH-1 rates were 2.6%
      versus 5.5% (RR: 0.49; 95% CI: 0.27-0.88); PPH-2 rates were 3.8% versus 10.8%
      (RR: 0.35; 95% CI: 0.18-0.63), and PPH-3 rates were similar to those of PPH-2.
      Compared to women in control clusters, those in the intervention clusters lost
      45.1 mL (17.7-72.6) less blood. There were no cases of oxytocin use before
      delivery of the baby and no major adverse events requiring notification of the
      institutional review boards. Limitations include an unblinded trial and
      imbalanced numbers of participants, favoring controls. CONCLUSION: Maternal
      health care planners can consider adapting this model to extend the use of
      oxytocin into peripheral settings including, in some contexts, home births. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01108289 Please see later in the article for
      the Editors' Summary.

PMID- 24130464
TI  - The prevention of postpartum hemorrhage in the community.
AB  - Joao Paulo Souza discusses the implications of a study by Cynthia Stanton and
      colleagues for the prevention and management of postpartum hemorrhage in the
      community, particularly in low-income countries, and outlines the remaining
      challenges. Please see later in the article for the Editors' Summary. 

PMID- 24130465
TI  - GINI: from ISH images to gene interaction networks.
AB  - Accurate inference of molecular and functional interactions among genes,
      especially in multicellular organisms such as Drosophila, often requires
      statistical analysis of correlations not only between the magnitudes of gene
      expressions, but also between their temporal-spatial patterns. The ISH (in-situ
      hybridization)-based gene expression micro-imaging technology offers an effective
      approach to perform large-scale spatial-temporal profiling of whole-body mRNA
      abundance. However, analytical tools for discovering gene interactions from such
      data remain an open challenge due to various reasons, including difficulties in
      extracting canonical representations of gene activities from images, and in
      inference of statistically meaningful networks from such representations. In this
      paper, we present GINI, a machine learning system for inferring gene interaction
      networks from Drosophila embryonic ISH images. GINI builds on a computer-vision
      inspired vector-space representation of the spatial pattern of gene expression in
      ISH images, enabled by our recently developed [Formula: see text] system; and a
      new multi-instance-kernel algorithm that learns a sparse Markov network model, in
      which, every gene (i.e., node) in the network is represented by a vector-valued
      spatial pattern rather than a scalar-valued gene intensity as in conventional
      approaches such as a Gaussian graphical model. By capturing the notion of spatial
      similarity of gene expression, and at the same time properly taking into account
      the presence of multiple images per gene via multi-instance kernels, GINI is well
      positioned to infer statistically sound, and biologically meaningful gene
      interaction networks from image data. Using both synthetic data and a small
      manually curated data set, we demonstrate the effectiveness of our approach in
      network building. Furthermore, we report results on a large publicly available
      collection of Drosophila embryonic ISH images from the Berkeley Drosophila Genome
      Project, where GINI makes novel and interesting predictions of gene interactions.
      Software for GINI is available at
      http://sailing.cs.cmu.edu/Drosophila_ISH_images/ 

PMID- 24130467
TI  - A genome-scale integration and analysis of Lactococcus lactis translation data.
AB  - Protein synthesis is a template polymerization process composed by three main
      steps: initiation, elongation, and termination. During translation, ribosomes are
      engaged into polysomes whose size is used for the quantitative characterization
      of translatome. However, simultaneous transcription and translation in the
      bacterial cytosol complicates the analysis of translatome data. We established a
      procedure for robust estimation of the ribosomal density in hundreds of genes
      from Lactococcus lactis polysome size measurements. We used a mechanistic model
      of translation to integrate the information about the ribosomal density and for
      the first time we estimated the protein synthesis rate for each gene and
      identified the rate limiting steps. Contrary to conventional considerations, we
      find significant number of genes to be elongation limited. This number increases
      during stress conditions compared to optimal growth and proteins synthesized at
      maximum rate are predominantly elongation limited. Consistent with bacterial
      physiology, we found proteins with similar rate and control characteristics
      belonging to the same functional categories. Under stress conditions, we found
      that synthesis rate of regulatory proteins is becoming comparable to proteins
      favored under optimal growth. These findings suggest that the coupling of
      metabolic states and protein synthesis is more important than previously thought.

PMID- 24130466
TI  - Human genome replication proceeds through four chromatin states.
AB  - Advances in genomic studies have led to significant progress in understanding the
      epigenetically controlled interplay between chromatin structure and nuclear
      functions. Epigenetic modifications were shown to play a key role in
      transcription regulation and genome activity during development and
      differentiation or in response to the environment. Paradoxically, the molecular
      mechanisms that regulate the initiation and the maintenance of the spatio
      temporal replication program in higher eukaryotes, and in particular their links
      to epigenetic modifications, still remain elusive. By integrative analysis of the
      genome-wide distributions of thirteen epigenetic marks in the human cell line
      K562, at the 100 kb resolution of corresponding mean replication timing (MRT)
      data, we identify four major groups of chromatin marks with shared features.
      These states have different MRT, namely from early to late replicating,
      replication proceeds though a transcriptionally active euchromatin state (C1), a
      repressive type of chromatin (C2) associated with polycomb complexes, a silent
      state (C3) not enriched in any available marks, and a gene poor HP1-associated
      heterochromatin state (C4). When mapping these chromatin states inside the
      megabase-sized U-domains (U-shaped MRT profile) covering about 50% of the human
      genome, we reveal that the associated replication fork polarity gradient
      corresponds to a directional path across the four chromatin states, from C1 at U
      domains borders followed by C2, C3 and C4 at centers. Analysis of the other
      genome half is consistent with early and late replication loci occurring in
      separate compartments, the former correspond to gene-rich, high-GC domains of
      intermingled chromatin states C1 and C2, whereas the latter correspond to gene
      poor, low-GC domains of alternating chromatin states C3 and C4 or long C4
      domains. This new segmentation sheds a new light on the epigenetic regulation of
      the spatio-temporal replication program in human and provides a framework for
      further studies in different cell types, in both health and disease. 

PMID- 24130468
TI  - Simple topological features reflect dynamics and modularity in protein
      interaction networks.
AB  - The availability of large-scale protein-protein interaction networks for numerous
      organisms provides an opportunity to comprehensively analyze whether simple
      properties of proteins are predictive of the roles they play in the functional
      organization of the cell. We begin by re-examining an influential but
      controversial characterization of the dynamic modularity of the S. cerevisiae
      interactome that incorporated gene expression data into network analysis. We
      analyse the protein-protein interaction networks of five organisms, S.
      cerevisiae, H. sapiens, D. melanogaster, A. thaliana, and E. coli, and confirm
      significant and consistent functional and structural differences between hub
      proteins that are co-expressed with their interacting partners and those that are
      not, and support the view that the former tend to be intramodular whereas the
      latter tend to be intermodular. However, we also demonstrate that in each of
      these organisms, simple topological measures are significantly correlated with
      the average co-expression of a hub with its partners, independent of any
      classification, and therefore also reflect protein intra- and inter- modularity.
      Further, cross-interactomic analysis demonstrates that these simple topological
      characteristics of hub proteins tend to be conserved across organisms. Overall,
      we give evidence that purely topological features of static interaction networks
      reflect aspects of the dynamics and modularity of interactomes as well as
      previous measures incorporating expression data, and are a powerful means for
      understanding the dynamic roles of hubs in interactomes. 

PMID- 24130469
TI  - A horizontal alignment tool for numerical trend discovery in sequence data:
      application to protein hydropathy.
AB  - An algorithm is presented that returns the optimal pairwise gapped alignment of
      two sets of signed numerical sequence values. One distinguishing feature of this
      algorithm is a flexible comparison engine (based on both relative shape and
      absolute similarity measures) that does not rely on explicit gap penalties.
      Additionally, an empirical probability model is developed to estimate the
      significance of the returned alignment with respect to randomized data. The
      algorithm's utility for biological hypothesis formulation is demonstrated with
      test cases including database search and pairwise alignment of protein
      hydropathy. However, the algorithm and probability model could possibly be
      extended to accommodate other diverse types of protein or nucleic acid data,
      including positional thermodynamic stability and mRNA translation efficiency. The
      algorithm requires only numerical values as input and will readily compare data
      other than protein hydropathy. The tool is therefore expected to complement,
      rather than replace, existing sequence and structure based tools and may inform
      medical discovery, as exemplified by proposed similarity between a chlamydial
      ORFan protein and bacterial colicin pore-forming domain. The source code,
      documentation, and a basic web-server application are available. 

PMID- 24130470
TI  - Feature selection methods for identifying genetic determinants of host species in
      RNA viruses.
AB  - Despite environmental, social and ecological dependencies, emergence of zoonotic
      viruses in human populations is clearly also affected by genetic factors which
      determine cross-species transmission potential. RNA viruses pose an interesting
      case study given their mutation rates are orders of magnitude higher than any
      other pathogen--as reflected by the recent emergence of SARS and Influenza for
      example. Here, we show how feature selection techniques can be used to reliably
      classify viral sequences by host species, and to identify the crucial minority of
      host-specific sites in pathogen genomic data. The variability in alleles at those
      sites can be translated into prediction probabilities that a particular pathogen
      isolate is adapted to a given host. We illustrate the power of these methods by:
      1) identifying the sites explaining SARS coronavirus differences between human,
      bat and palm civet samples; 2) showing how cross species jumps of rabies virus
      among bat populations can be readily identified; and 3) de novo identification of
      likely functional influenza host discriminant markers.

PMID- 24130471
TI  - Inferring evolutionary histories of pathway regulation from transcriptional
      profiling data.
AB  - One of the outstanding challenges in comparative genomics is to interpret the
      evolutionary importance of regulatory variation between species. Rigorous
      molecular evolution-based methods to infer evidence for natural selection from
      expression data are at a premium in the field, and to date, phylogenetic
      approaches have not been well-suited to address the question in the small sets of
      taxa profiled in standard surveys of gene expression. We have developed a
      strategy to infer evolutionary histories from expression profiles by analyzing
      suites of genes of common function. In a manner conceptually similar to molecular
      evolution models in which the evolutionary rates of DNA sequence at multiple loci
      follow a gamma distribution, we modeled expression of the genes of an a priori
      defined pathway with rates drawn from an inverse gamma distribution. We then
      developed a fitting strategy to infer the parameters of this distribution from
      expression measurements, and to identify gene groups whose expression patterns
      were consistent with evolutionary constraint or rapid evolution in particular
      species. Simulations confirmed the power and accuracy of our inference method. As
      an experimental testbed for our approach, we generated and analyzed
      transcriptional profiles of four Saccharomyces yeasts. The results revealed
      pathways with signatures of constrained and accelerated regulatory evolution in
      individual yeasts and across the phylogeny, highlighting the prevalence of
      pathway-level expression change during the divergence of yeast species. We
      anticipate that our pathway-based phylogenetic approach will be of broad utility
      in the search to understand the evolutionary relevance of regulatory change. 

PMID- 24130472
TI  - A simple rule for dendritic spine and axonal bouton formation can account for
      cortical reorganization after focal retinal lesions.
AB  - Lasting alterations in sensory input trigger massive structural and functional
      adaptations in cortical networks. The principles governing these experience
      dependent changes are, however, poorly understood. Here, we examine whether a
      simple rule based on the neurons' need for homeostasis in electrical activity may
      serve as driving force for cortical reorganization. According to this rule, a
      neuron creates new spines and boutons when its level of electrical activity is
      below a homeostatic set-point and decreases the number of spines and boutons when
      its activity exceeds this set-point. In addition, neurons need a minimum level of
      activity to form spines and boutons. Spine and bouton formation depends solely on
      the neuron's own activity level, and synapses are formed by merging spines and
      boutons independently of activity. Using a novel computational model, we show
      that this simple growth rule produces neuron and network changes as observed in
      the visual cortex after focal retinal lesions. In the model, as in the cortex,
      the turnover of dendritic spines was increased strongest in the center of the
      lesion projection zone, while axonal boutons displayed a marked overshoot
      followed by pruning. Moreover, the decrease in external input was compensated for
      by the formation of new horizontal connections, which caused a retinotopic
      remapping. Homeostatic regulation may provide a unifying framework for
      understanding cortical reorganization, including network repair in degenerative
      diseases or following focal stroke. 

PMID- 24130473
TI  - Virus encoded MHC-like decoys diversify the inhibitory KIR repertoire.
AB  - Natural killer (NK) cells are circulating lymphocytes that play an important role
      in the control of viral infections and tumors. Their functions are regulated by
      several activating and inhibitory receptors. A subset of these receptors in human
      NK cells are the killer immunoglobulin-like receptors (KIRs), which interact with
      the highly polymorphic MHC class I molecules. One important function of NK cells
      is to detect cells that have down-regulated MHC expression (missing-self).
      Because MHC molecules have non polymorphic regions, their expression could have
      been monitored with a limited set of monomorphic receptors. Surprisingly, the KIR
      family has a remarkable genetic diversity, the function of which remains poorly
      understood. The mouse cytomegalovirus (MCMV) is able to evade NK cell responses
      by coding "decoy" molecules that mimic MHC class I. This interaction was
      suggested to have driven the evolution of novel NK cell receptors. Inspired by
      the MCMV system, we develop an agent-based model of a host population infected
      with viruses that are able to evolve MHC down-regulation and decoy molecules. Our
      simulations show that specific recognition of MHC class I molecules by inhibitory
      KIRs provides excellent protection against viruses evolving decoys, and that the
      diversity of inhibitory KIRs will subsequently evolve as a result of the required
      discrimination between host MHC molecules and decoy molecules. 

PMID- 24130474
TI  - A network approach to analyzing highly recombinant malaria parasite genes.
AB  - The var genes of the human malaria parasite Plasmodium falciparum present a
      challenge to population geneticists due to their extreme diversity, which is
      generated by high rates of recombination. These genes encode a primary antigen
      protein called PfEMP1, which is expressed on the surface of infected red blood
      cells and elicits protective immune responses. Var gene sequences are
      characterized by pronounced mosaicism, precluding the use of traditional
      phylogenetic tools that require bifurcating tree-like evolutionary relationships.
      We present a new method that identifies highly variable regions (HVRs), and then
      maps each HVR to a complex network in which each sequence is a node and two nodes
      are linked if they share an exact match of significant length. Here, networks of
      var genes that recombine freely are expected to have a uniformly random
      structure, but constraints on recombination will produce network communities that
      we identify using a stochastic block model. We validate this method on synthetic
      data, showing that it correctly recovers populations of constrained
      recombination, before applying it to the Duffy Binding Like-alpha (DBLalpha)
      domain of var genes. We find nine HVRs whose network communities map in
      distinctive ways to known DBLalpha classifications and clinical phenotypes. We
      show that the recombinational constraints of some HVRs are correlated, while
      others are independent. These findings suggest that this micromodular structuring
      facilitates independent evolutionary trajectories of neighboring mosaic regions,
      allowing the parasite to retain protein function while generating enormous
      sequence diversity. Our approach therefore offers a rigorous method for analyzing
      evolutionary constraints in var genes, and is also flexible enough to be easily
      applied more generally to any highly recombinant sequences. 

PMID- 24130476
TI  - The cell biology of Leishmania: how to teach using animations.

PMID- 24130475
TI  - Machines vs. ensembles: effective MAPK signaling through heterogeneous sets of
      protein complexes.
AB  - Despite the importance of intracellular signaling networks, there is currently no
      consensus regarding the fundamental nature of the protein complexes such networks
      employ. One prominent view involves stable signaling machines with well-defined
      quaternary structures. The combinatorial complexity of signaling networks has led
      to an opposing perspective, namely that signaling proceeds via heterogeneous
      pleiomorphic ensembles of transient complexes. Since many hypotheses regarding
      network function rely on how we conceptualize signaling complexes, resolving this
      issue is a central problem in systems biology. Unfortunately, direct experimental
      characterization of these complexes has proven technologically difficult, while
      combinatorial complexity has prevented traditional modeling methods from
      approaching this question. Here we employ rule-based modeling, a technique that
      overcomes these limitations, to construct a model of the yeast pheromone
      signaling network. We found that this model exhibits significant ensemble
      character while generating reliable responses that match experimental
      observations. To contrast the ensemble behavior, we constructed a model that
      employs hierarchical assembly pathways to produce scaffold-based signaling
      machines. We found that this machine model could not replicate the experimentally
      observed combinatorial inhibition that arises when the scaffold is overexpressed.
      This finding provides evidence against the hierarchical assembly of machines in
      the pheromone signaling network and suggests that machines and ensembles may
      serve distinct purposes in vivo. In some cases, e.g. core enzymatic activities
      like protein synthesis and degradation, machines assembled via hierarchical
      energy landscapes may provide functional stability for the cell. In other cases,
      such as signaling, ensembles may represent a form of weak linkage, facilitating
      variation and plasticity in network evolution. The capacity of ensembles to
      signal effectively will ultimately shape how we conceptualize the function,
      evolution and engineering of signaling networks. 

PMID- 24130477
TI  - Antivirulence therapy for animal production: filling an arsenal with novel
      weapons for sustainable disease control.

PMID- 24130478
TI  - Fungal adenylyl cyclase acts as a signal sensor and integrator and plays a
      central role in interaction with bacteria.

PMID- 24130479
TI  - Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10
      producing CD4+ T cells.
AB  - Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which,
      after primary infection, persists in the host for life. In healthy individuals,
      the virus is well controlled by the HCMV-specific T cell response. A key feature
      of this persistence, in the face of a normally robust host immune response, is
      the establishment of viral latency. In contrast to lytic infection, which is
      characterised by extensive viral gene expression and virus production, long-term
      latency in cells of the myeloid lineage is characterised by highly restricted
      expression of viral genes, including UL138 and LUNA. Here we report that both
      UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV
      seropositive subjects and that this response is principally CD4+ T cell mediated.
      These UL138-specific CD4+ T cells are able to mediate MHC class II restricted
      cytotoxicity and, importantly, show IFNgamma effector function in the context of
      both lytic and latent infection. Furthermore, in contrast to CDCD4+ T cells
      specific to antigens expressed solely during lytic infection, both the UL138 and
      LUNA-specific CD4+ T cell responses included CD4+ T cells that secreted the
      immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4+ T
      cells are directed against latently expressed US28 and UL111A. Taken together,
      our data show that latency-associated gene products of HCMV generate CD4+ T cell
      responses in vivo, which are able to elicit effector function in response to both
      lytic and latently infected cells. Importantly and in contrast to CD4+ T cell
      populations, which recognise antigens solely expressed during lytic infection,
      include a subset of cells that secrete the immunosuppressive cytokine cIL-10.
      This suggests that HCMV skews the T cell responses to latency-associated antigens
      to one that is overall suppressive in order to sustain latent carriage in vivo.

PMID- 24130480
TI  - Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity
      and protection of virulence-associated cell wall proteins.
AB  - Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an
      unusual family of staphylococcal adhesive proteins that contain long stretches of
      serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is
      clumping factor A (ClfA), a key virulence factor that mediates adhesion to host
      tissues by binding to extracellular matrix proteins such as fibrinogen. However,
      the biological siginificance of the SDR-domain and its implication for
      pathogenesis remain poorly understood. Here, we identified two novel bacterial
      glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two
      bacterial species. Genetic and biochemical data demonstrated that these two
      glycosyltransferases directly bind and covalently link N-acetylglucosamine
      (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending
      the sugar residues proximal to the target Ser-Asp repeats, followed by additional
      modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an
      immunodominant epitope for highly opsonic human antibodies, which represent up to
      1% of total human IgG. Deletion of these glycosyltransferases renders SDR
      proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus,
      SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them
      against host proteolytic activity, and yet generates major eptopes for the human
      anti-staphylococcal antibody response, which may represent an ongoing competition
      between host and pathogen. 

PMID- 24130481
TI  - New world bats harbor diverse influenza A viruses.
AB  - Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir
      in nature. The recent discovery of influenza viruses of a new H17N10 subtype in
      Central American fruit bats suggests that other New World species may similarly
      carry divergent influenza viruses. Using consensus degenerate RT-PCR, we
      identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit
      bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18
      protein indicated that several Peruvian bat species were infected by this virus.
      Phylogenetic analyses demonstrate that, in some gene segments, New World bats
      harbor more influenza virus genetic diversity than all other mammalian and avian
      species combined, indicative of a long-standing host-virus association.
      Structural and functional analyses of the hemagglutinin and neuraminidase
      indicate that sialic acid is not a ligand for virus attachment nor a substrate
      for release, suggesting a unique mode of influenza A virus attachment and
      activation of membrane fusion for entry into host cells. Taken together, these
      findings indicate that bats constitute a potentially important and likely ancient
      reservoir for a diverse pool of influenza viruses. 

PMID- 24130482
TI  - Type I interferon upregulates Bak and contributes to T cell loss during human
      immunodeficiency virus (HIV) infection.
AB  - The role of Type I interferon (IFN) during pathogenic HIV and SIV infections
      remains unclear, with conflicting observations suggesting protective versus
      immunopathological effects. We therefore examined the effect of IFNalpha/beta on
      T cell death and viremia in HIV infection. Ex vivo analysis of eight pro- and
      anti-apoptotic molecules in chronic HIV-1 infection revealed that pro-apoptotic
      Bak was increased in CD4+ T cells and correlated directly with sensitivity to
      CD95/Fas-mediated apoptosis and inversely with CD4+ T cell counts. Apoptosis
      sensitivity and Bak expression were primarily increased in effector memory T
      cells. Knockdown of Bak by RNA interference inhibited CD95/Fas-induced death of T
      cells from HIV-1-infected individuals. In HIV-1-infected patients, IFNalpha
      stimulated gene expression correlated positively with ex vivo T cell Bak levels,
      CD95/Fas-mediated apoptosis and viremia and negatively with CD4+ T cell counts.
      In vitro IFNalpha/beta stimulation enhanced Bak expression, CD95/Fas expression
      and CD95/Fas-mediated apoptosis in healthy donor T cells and induced death of HIV
      specific CD8+ T cells from HIV-1-infected patients. HIV-1 in vitro sensitized T
      cells to CD95/Fas-induced apoptosis and this was Toll-like receptor (TLR)7/9- and
      Type I IFN-dependent. This sensitization by HIV-1 was due to an indirect effect
      on T cells, as it occurred in peripheral blood mononuclear cell cultures but not
      purified CD4+ T cells. Finally, peak IFNalpha levels and viral loads correlated
      negatively during acute SIV infection suggesting a potential antiviral effect,
      but positively during chronic SIV infection indicating that either the virus
      drives IFNalpha production or IFNalpha may facilitate loss of viral control. The
      above findings indicate stage-specific opposing effects of Type I IFNs during HIV
      1 infection and suggest a novel mechanism by which these cytokines contribute to
      T cell depletion, dysregulation of cellular immunity and disease progression. 

PMID- 24130483
TI  - Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument
      protein deneddylase to the nucleus of productively infected cells.
AB  - The large tegument proteins of herpesviruses contain N-terminal cysteine
      proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but
      the function of the enzymes during virus replication remains largely unknown.
      Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found
      that induction of the productive virus cycle does not affect the total level of
      ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8
      adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin
      degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the
      nucleus, while cytoplasmic CRLs and their substrates are not affected. The
      inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which
      inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA
      replication. Targeting of the deneddylase activity to the nucleus is dependent on
      processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1
      severely impairs viral DNA synthesis and the release of infectious virus,
      pointing a previously unrecognized role of the cellular response to danger
      signals triggered by EBV reactivation in promoting virus replication. 

PMID- 24130484
TI  - An RxLR effector from Phytophthora infestans prevents re-localisation of two
      plant NAC transcription factors from the endoplasmic reticulum to the nucleus.
AB  - The potato late blight pathogen Phytophthora infestans secretes an array of
      effector proteins thought to act in its hosts by disarming defences and promoting
      pathogen colonisation. However, little is known about the host targets of these
      effectors and how they are manipulated by the pathogen. This work describes the
      identification of two putative membrane-associated NAC transcription factors (TF)
      as the host targets of the RxLR effector PITG_03192 (Pi03192). The effector
      interacts with NAC Targeted by Phytophthora (NTP) 1 and NTP2 at the endoplasmic
      reticulum (ER) membrane, where these proteins are localised. Transcripts of NTP1
      and NTP2 rapidly accumulate following treatment with culture filtrate (CF) from
      in vitro grown P. infestans, which acts as a mixture of Phytophthora PAMPs and
      elicitors, but significantly decrease during P. infestans infection, indicating
      that pathogen activity may prevent their up-regulation. Silencing of NTP1 or NTP2
      in the model host plant Nicotiana benthamiana increases susceptibility to P.
      infestans, whereas silencing of Pi03192 in P. infestans reduces pathogenicity.
      Transient expression of Pi03192 in planta restores pathogenicity of the Pi03192
      silenced line. Moreover, colonisation by the Pi03192-silenced line is
      significantly enhanced on N. benthamiana plants in which either NTP1 or NTP2 have
      been silenced. StNTP1 and StNTP2 proteins are released from the ER membrane
      following treatment with P. infestans CF and accumulate in the nucleus, after
      which they are rapidly turned over by the 26S proteasome. In contrast, treatment
      with the defined PAMP flg22 fails to up-regulate NTP1 and NTP2, or promote re
      localisation of their protein products to the nucleus, indicating that these
      events follow perception of a component of CF that appears to be independent of
      the FLS2/flg22 pathway. Importantly, Pi03192 prevents CF-triggered re
      localisation of StNTP1 and StNTP2 from the ER into the nucleus, revealing a novel
      effector mode-of-action to promote disease progression. 

PMID- 24130485
TI  - MAIT cells detect and efficiently lyse bacterially-infected epithelial cells.
AB  - Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect
      a large variety of bacteria and yeasts. This recognition depends on the detection
      of microbial compounds presented by the evolutionarily conserved major
      histocompatibility-complex (MHC) class I molecule, MR1. Here we show that MAIT
      cells display cytotoxic activity towards MR1 overexpressing non-hematopoietic
      cells cocultured with bacteria. The NK receptor, CD161, highly expressed by MAIT
      cells, modulated the cytokine but not the cytotoxic response triggered by
      bacteria infected cells. MAIT cells are also activated by and kill epithelial
      cells expressing endogenous levels of MRI after infection with the invasive
      bacteria Shigella flexneri. In contrast, MAIT cells were not activated by
      epithelial cells infected by Salmonella enterica Typhimurium. Finally, MAIT cells
      are activated in human volunteers receiving an attenuated strain of Shigella
      dysenteriae-1 tested as a potential vaccine. Thus, in humans, MAIT cells are the
      most abundant T cell subset able to detect and kill bacteria infected cells. 

PMID- 24130486
TI  - Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent
      cross-reactive neutralizing human monoclonal antibody.
AB  - The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly
      pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible
      for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The
      high morbidity and mortality rates associated with infection and lack of licensed
      antiviral therapies make the henipaviruses a potential biological threat to
      humans and livestock. Henipavirus entry is initiated by the attachment of the G
      envelope glycoprotein to host cell membrane receptors. Previously, henipavirus
      neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV
      G glycoprotein and a human naive antibody library. One cross-reactive and
      receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post
      exposure therapy in two animal models of NiV and HeV infection, has been used in
      several people on a compassionate use basis, and is currently in development for
      use in humans. Here, we report the crystal structure of the complex of HeV-G with
      m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This
      structure provides detailed insight into the mechanism of HeV and NiV
      neutralization by m102.4, and serves as a blueprint for further optimization of
      m102.4 as a therapeutic agent and for the development of entry inhibitors and
      vaccines. 

PMID- 24130487
TI  - A structure-guided mutation in the major capsid protein retargets BK
      polyomavirus.
AB  - Viruses within a family often vary in their cellular tropism and pathogenicity.
      In many cases, these variations are due to viruses switching their specificity
      from one cell surface receptor to another. The structural requirements that
      underlie such receptor switching are not well understood especially for
      carbohydrate-binding viruses, as methods capable of structure-specificity studies
      are only relatively recently being developed for carbohydrates. We have
      characterized the receptor specificity, structure and infectivity of the human
      polyomavirus BKPyV, the causative agent of polyomavirus-associated nephropathy,
      and uncover a molecular switch for binding different carbohydrate receptors. We
      show that the b-series gangliosides GD3, GD2, GD1b and GT1b all can serve as
      receptors for BKPyV. The crystal structure of the BKPyV capsid protein VP1 in
      complex with GD3 reveals contacts with two sialic acid moieties in the receptor,
      providing a basis for the observed specificity. Comparison with the structure of
      simian virus 40 (SV40) VP1 bound to ganglioside GM1 identifies the amino acid at
      position 68 as a determinant of specificity. Mutation of this residue from lysine
      in BKPyV to serine in SV40 switches the receptor specificity of BKPyV from GD3 to
      GM1 both in vitro and in cell culture. Our findings highlight the plasticity of
      viral receptor binding sites and form a template to retarget viruses to different
      receptors and cell types. 

PMID- 24130488
TI  - Structure of a bimodular botulinum neurotoxin complex provides insights into its
      oral toxicity.
AB  - Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the
      fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released
      together with several auxiliary proteins as progenitor toxin complexes (PTCs) to
      become highly potent oral poisons. Here, we report the structure of a ~760 kDa 14
      subunit large PTC of serotype A (L-PTC/A) and reveal insight into its absorption
      mechanism. Using a combination of X-ray crystallography, electron microscopy, and
      functional studies, we found that L-PTC/A consists of two structurally and
      functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects
      BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in
      the harsh environment of the gastrointestinal tract. BoNT absorption is mediated
      by nine glycan-binding sites on the dodecameric sub-complex that forms
      multivalent interactions with carbohydrate receptors on intestinal epithelial
      cells. We identified monosaccharides that blocked oral BoNT intoxication in mice,
      which suggests a new strategy for the development of preventive countermeasures
      for BoNTs based on carbohydrate receptor mimicry. 

PMID- 24130489
TI  - Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.
AB  - The study of HIV-infected "controllers" who are able to maintain low levels of
      plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide
      insights for HIV cure and vaccine strategies. Despite maintaining very low levels
      of plasma viremia, controllers have elevated immune activation and accelerated
      atherosclerosis. However, the degree to which low-level replication contributes
      to these phenomena is not known. Sixteen asymptomatic controllers were
      prospectively treated with ART for 24 weeks. Controllers had a statistically
      significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART.
      Markers of T cell activation/dysfunction in blood and gut mucosa also decreased
      substantially with ART. Similar reductions were observed in the subset of "elite"
      controllers with pre-ART plasma HIV RNA levels below conventional assays (<40
      copies/mL). These data confirm that HIV replication persists in controllers and
      contributes to a chronic inflammatory state. ART should be considered for these
      individuals (ClinicalTrials.gov NCT01025427). 

PMID- 24130490
TI  - Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket
      within the HIV-1 capsid protein to mediate lentiviral infectivity.
AB  - Lentiviruses can infect non-dividing cells, and various cellular transport
      proteins provide crucial functions for lentiviral nuclear entry and integration.
      We previously showed that the viral capsid (CA) protein mediated the dependency
      on cellular nucleoporin (NUP) 153 during HIV-1 infection, and now demonstrate a
      direct interaction between the CA N-terminal domain and the phenylalanine-glycine
      (FG)-repeat enriched NUP153 C-terminal domain (NUP153(C)). NUP153(C) fused to the
      effector domains of the rhesus Trim5alpha restriction factor (Trim-NUP153(C))
      potently restricted HIV-1, providing an intracellular readout for the NUP153(C)
      CA interaction during retroviral infection. Primate lentiviruses and equine
      infectious anemia virus (EIAV) bound NUP153(C) under these conditions, results
      that correlated with direct binding between purified proteins in vitro. These
      binding phenotypes moreover correlated with the requirement for endogenous NUP153
      protein during virus infection. Mutagenesis experiments concordantly identified
      NUP153(C) and CA residues important for binding and lentiviral infectivity.
      Different FG motifs within NUP153(C) mediated binding to HIV-1 versus EIAV
      capsids. HIV-1 CA binding mapped to residues that line the common alpha helix 3/4
      hydrophobic pocket that also mediates binding to the small molecule PF-3450074
      (PF74) inhibitor and cleavage and polyadenylation specific factor 6 (CPSF6)
      protein, with Asn57 (Asp58 in EIAV) playing a particularly important role. PF74
      and CPSF6 accordingly each competed with NUP153(C) for binding to the HIV-1 CA
      pocket, and significantly higher concentrations of PF74 were needed to inhibit
      HIV-1 infection in the face of Trim-NUP153(C) expression or NUP153 knockdown.
      Correlation between CA mutant viral cell cycle and NUP153 dependencies moreover
      indicates that the NUP153(C)-CA interaction underlies the ability of HIV-1 to
      infect non-dividing cells. Our results highlight similar mechanisms of binding
      for disparate host factors to the same region of HIV-1 CA during viral ingress.
      We conclude that a subset of lentiviral CA proteins directly engage FG-motifs
      present on NUP153 to affect viral nuclear import.

PMID- 24130491
TI  - The differential mobilization of histones H3.1 and H3.3 by herpes simplex virus 1
      relates histone dynamics to the assembly of viral chromatin.
AB  - During lytic infections, HSV-1 genomes are assembled into unstable nucleosomes.
      The histones required for HSV-1 chromatin assembly, however, are in the cellular
      chromatin. We have shown that linker (H1) and core (H2B and H4) histones are
      mobilized during HSV-1 infection, and proposed that the mobilized histones are
      available for assembly into viral chromatin. However, the actual relevance of
      histone mobilization remained unknown. We now show that canonical H3.1 and
      variant H3.3 are also mobilized during HSV-1 infection. Mobilization required no
      HSV-1 protein expression, although immediate early or early proteins enhanced it.
      We used the previously known differential association of H3.3 and H3.1 with HSV-1
      DNA to test the relevance of histone mobilization. H3.3 binds to HSV-1 genomes
      first, whereas H3.1 only binds after HSV-1 DNA replication initiates.
      Consistently, H3.3 and H3.1 were differentially mobilized. H3.1 mobilization
      decreased with HSV-1 DNA replication, whereas H3.3 mobilization was largely
      unaffected by it. These results support a model in which previously mobilized
      H3.1 is immobilized by assembly into viral chromatin during HSV-1 DNA
      replication, whereas H3.3 is mobilized and assembled into HSV-1 chromatin
      throughout infection. The differential mobilizations of H3.3 and H3.1 are
      consistent with their differential assembly into viral chromatin. These data
      therefore relate nuclear histone dynamics to the composition of viral chromatin
      and provide the first evidence that histone mobilization relates to viral
      chromatin assembly. 

PMID- 24130492
TI  - Activation of the Cph1-dependent MAP kinase signaling pathway induces white
      opaque switching in Candida albicans.
AB  - Depending on the environmental conditions, the pathogenic yeast Candida albicans
      can undergo different developmental programs, which are controlled by dedicated
      transcription factors and upstream signaling pathways. C. albicans strains that
      are homozygous at the mating type locus can switch from the normal yeast form
      (white) to an elongated cell type (opaque), which is the mating-competent form of
      this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase
      signaling pathway to react to the presence of mating pheromone. However, while
      opaque cells employ the transcription factor Cph1 to induce the mating response,
      white cells recruit a different downstream transcription factor, Tec1, to promote
      the formation of a biofilm that facilitates mating of opaque cells in the
      population. The switch from the white to the opaque cell form is itself induced
      by environmental signals that result in the upregulation of the transcription
      factor Wor1, the master regulator of white-opaque switching. To get insight into
      the upstream signaling pathways controlling the switch, we expressed all C.
      albicans protein kinases from a tetracycline-inducible promoter in a switching
      competent strain. Screening of this library of strains showed that a hyperactive
      form of Ste11 lacking its N-terminal domain (Ste11(DeltaN467)) efficiently
      stimulated white cells to switch to the opaque phase, a behavior that did not
      occur in response to pheromone. Ste11(DeltaN467)-induced switching specifically
      required the downstream MAP kinase Cek1 and its target transcription factor Cph1,
      but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque
      switching in a Wor1-dependent manner. Therefore, depending on the activation
      mechanism, components of the pheromone-responsive MAP kinase pathway can be
      reconnected to stimulate an alternative developmental program, switching of white
      cells to the mating-competent opaque phase. 

PMID- 24130493
TI  - MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by
      targeting Rheb.
AB  - Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that
      infects one-third of the global population. It can live within macrophages owning
      to its ability to arrest phagolysosome biogenesis. Autophagy has recently been
      identified as an effective way to control the intracellular mycobacteria by
      enhancing phagosome maturation. In the present study, we demonstrate a novel role
      of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both
      in vivo and in vitro studies showed that miR-155 expression was significantly
      enhanced after mycobacterial infection. Forced expression of miR-155 accelerated
      the autophagic response in macrophages, thus promoting the maturation of
      mycobacterial phagosomes and decreasing the survival rate of intracellular
      mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial
      survival. However, macrophage-mediated mycobacterial phagocytosis was not
      affected after miR-155 overexpression or inhibition. Furthermore, blocking
      autophagy with specific inhibitor 3-methyladenine or silencing of autophagy
      related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and
      mycobacterial elimination. More importantly, our study demonstrated that miR-155
      bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb), a
      negative regulator of autophagy, accelerated the process of autophagy and
      sequential killing of intracellular mycobacteria by suppressing Rheb expression.
      Our results reveal a novel role of miR-155 in regulating autophagy-mediated
      mycobacterial elimination by targeting Rheb, and provide potential targets for
      clinical treatment. 

PMID- 24130494
TI  - IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth
      infection.
AB  - Type 2 immune responses are essential in protection against intestinal helminth
      infections. In this study we show that IL-22, a cytokine important in defence
      against bacterial infections in the intestinal tract, is also a critical mediator
      of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a
      rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite
      normal levels of type 2 cytokine production. The impaired worm expulsion
      correlated with reduced goblet cell hyperplasia and reduced expression of goblet
      cell markers. We further confirmed our findings in a second nematode model, the
      murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a
      similar phenotype to that seen in N.brasiliensis infection, with impaired worm
      expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis
      demonstrated that IL-22 is able to directly induce the expression of several
      goblet cell markers, including mucins. Taken together, our findings reveal that
      IL-22 plays an important role in goblet cell activation, and thus, a key role in
      anti-helminth immunity. 

PMID- 24130495
TI  - Dual function of CD81 in influenza virus uncoating and budding.
AB  - As an obligatory pathogen, influenza virus co-opts host cell machinery to harbor
      infection and to produce progeny viruses. In order to characterize the virus-host
      cell interactions, several genome-wide siRNA screens and proteomic analyses have
      been performed recently to identify host factors involved in influenza virus
      infection. CD81 has emerged as one of the top candidates in two siRNA screens and
      one proteomic study. The exact role played by CD81 in influenza infection,
      however, has not been elucidated thus far. In this work, we examined the effect
      of CD81 depletion on the major steps of the influenza infection. We found that
      CD81 primarily affected virus infection at two stages: viral uncoating during
      entry and virus budding. CD81 marked a specific endosomal population and about
      half of the fused influenza virus particles underwent fusion within the CD81
      positive endosomes. Depletion of CD81 resulted in a substantial defect in viral
      fusion and infection. During virus assembly, CD81 was recruited to virus budding
      site on the plasma membrane, and in particular, to specific sub-viral locations.
      For spherical and slightly elongated influenza virus, CD81 was localized at both
      the growing tip and the budding neck of the progeny viruses. CD81 knockdown led
      to a budding defect and resulted in elongated budding virions with a higher
      propensity to remain attached to the plasma membrane. Progeny virus production
      was markedly reduced in CD81-knockdown cells even when the uncoating defect was
      compensated. In filamentous virus, CD81 was distributed at multiple sites along
      the viral filament. Taken together, these results demonstrate important roles of
      CD81 in both entry and budding stages of the influenza infection cycle. 

PMID- 24130496
TI  - Quaternary structure of pathological prion protein as a determining factor of
      strain-specific prion replication dynamics.
AB  - Prions are proteinaceous infectious agents responsible for fatal
      neurodegenerative diseases in animals and humans. They are essentially composed
      of PrP(Sc), an aggregated, misfolded conformer of the ubiquitously expressed host
      encoded prion protein (PrP(C)). Stable variations in PrP(Sc) conformation are
      assumed to encode the phenotypically tangible prion strains diversity. However
      the direct contribution of PrP(Sc) quaternary structure to the strain biological
      information remains mostly unknown. Applying a sedimentation velocity
      fractionation technique to a panel of ovine prion strains, classified as fast and
      slow according to their incubation time in ovine PrP transgenic mice, has
      previously led to the observation that the relationship between prion infectivity
      and PrP(Sc) quaternary structure was not univocal. For the fast strains
      specifically, infectivity sedimented slowly and segregated from the bulk of
      proteinase-K resistant PrP(Sc). To carefully separate the respective
      contributions of size and density to this hydrodynamic behavior, we performed
      sedimentation at the equilibrium and varied the solubilization conditions. The
      density profile of prion infectivity and proteinase-K resistant PrP(Sc) tended to
      overlap whatever the strain, fast or slow, leaving only size as the main
      responsible factor for the specific velocity properties of the fast strain most
      infectious component. We further show that this velocity-isolable population of
      discrete assemblies perfectly resists limited proteolysis and that its templating
      activity, as assessed by protein misfolding cyclic amplification outcompetes by
      several orders of magnitude that of the bulk of larger size PrP(Sc) aggregates.
      Together, the tight correlation between small size, conversion efficiency and
      duration of disease establishes PrP(Sc) quaternary structure as a determining
      factor of prion replication dynamics. For certain strains, a subset of PrP
      assemblies appears to be the best template for prion replication. This has
      important implications for fundamental studies on prions. 

PMID- 24130497
TI  - O-mannosylation of the Mycobacterium tuberculosis adhesin Apa is crucial for T
      cell antigenicity during infection but is expendable for protection.
AB  - Glycosylation is the most abundant post-translational polypeptide chain
      modification in nature. Although carbohydrate modification of protein antigens
      from many microbial pathogens constitutes important components of B cell
      epitopes, the role in T cell immunity is not completely understood. Here, using
      ELISPOT and polychromatic flow cytometry, we show that O-mannosylation of the
      adhesin, Apa, of Mycobacterium tuberculosis (Mtb) is crucial for its T cell
      antigenicity in humans and mice after infection. However, subunit vaccination
      with both mannosylated and non-mannosylated Apa induced a comparable magnitude
      and quality of T cell response and imparted similar levels of protection against
      Mtb challenge in mice. Both forms equally improved waning BCG vaccine-induced
      protection in elderly mice after subunit boosting. Thus, O-mannosylation of Apa
      is required for antigenicity but appears to be dispensable for its immunogenicity
      and protective efficacy in mice. These results have implications for the
      development of subunit vaccines using post-translationally modified proteins such
      as glycoproteins against infectious diseases like tuberculosis. 

PMID- 24130498
TI  - CXCR3-dependent CD4+ T cells are required to activate inflammatory monocytes for
      defense against intestinal infection.
AB  - Chemokines and their receptors play a critical role in orchestrating immunity to
      microbial pathogens, including the orally acquired Th1-inducing protozoan
      parasite Toxoplasma gondii. Chemokine receptor CXCR3 is associated with Th1
      responses, and here we use bicistronic CXCR3-eGFP knock-in reporter mice to
      demonstrate upregulation of this chemokine receptor on CD4+ and CD8+ T
      lymphocytes during Toxoplasma infection. We show a critical role for CXCR3 in
      resistance to the parasite in the intestinal mucosa. Absence of the receptor in
      Cxcr3-/- mice resulted in selective loss of ability to control T. gondii
      specifically in the lamina propria compartment. CD4+ T cells were impaired both
      in their recruitment to the intestinal lamina propria and in their ability to
      secrete IFN-gamma upon stimulation. Local recruitment of CD11b+Ly6C/G+
      inflammatory monocytes, recently reported to be major anti-Toxoplasma effectors
      in the intestine, was not impacted by loss of CXCR3. However, inflammatory
      monocyte activation status, as measured by dual production of TNF-alpha and IL
      12, was severely impaired in Cxcr3-/- mice. Strikingly, adoptive transfer of wild
      type but not Ifngamma-/- CD4+ T lymphocytes into Cxcr3-/- animals prior to
      infection corrected the defect in inflammatory macrophage activation,
      simultaneously reversing the susceptibility phenotype of the knockout animals.
      Our results establish a central role for CXCR3 in coordinating innate and
      adaptive immunity, ensuring generation of Th1 effectors and their trafficking to
      the frontline of infection to program microbial killing by inflammatory
      monocytes.

PMID- 24130499
TI  - Regulation of innate responses during pre-patent schistosome infection provides
      an immune environment permissive for parasite development.
AB  - Blood flukes of the genus Schistosoma infect over 200 million people, causing
      granulomatous pathology with accompanying morbidity and mortality. As a
      consequence of extensive host-parasite co-evolution, schistosomes exhibit a
      complex relationship with their hosts, in which immunological factors are
      intimately linked with parasite development. Schistosomes fail to develop
      normally in immunodeficient mice, an outcome specifically dependent on the
      absence of CD4+ T cells. The role of CD4+ T cells in parasite development is
      indirect and mediated by interaction with innate cells, as repeated toll-like
      receptor 4 stimulation is sufficient to restore parasite development in
      immunodeficient mice in the absence of CD4+ T cells. Here we show that repeated
      stimulation of innate immunity by an endogenous danger signal can also restore
      parasite development and that both these stimuli, when administered repeatedly,
      lead to the regulation of innate responses. Supporting a role for regulation of
      innate responses in parasite development, we show that regulation of inflammation
      by neutralizing anti-TNF antibodies also restores parasite development in
      immunodeficient mice. Finally, we show that administration of IL-4 to
      immunodeficient mice to regulate inflammation by induction of type 2 responses
      also restores parasite development. These findings suggest that the type 2
      response driven by CD4+ T cells during pre-patent infection of immunocompetent
      hosts is exploited by schistosomes to complete their development to
      reproductively mature adult parasites.

PMID- 24130500
TI  - Haemophilus responses to nutritional immunity: epigenetic and morphological
      contribution to biofilm architecture, invasion, persistence and disease severity.
AB  - In an effort to suppress microbial outgrowth, the host sequesters essential
      nutrients in a process termed nutritional immunity. However, inflammatory
      responses to bacterial insult can restore nutritional resources. Given that
      nutrient availability modulates virulence factor production and biofilm formation
      by other bacterial species, we hypothesized that fluctuations in heme-iron
      availability, particularly at privileged sites, would similarly influence
      Haemophilus biofilm formation and pathogenesis. Thus, we cultured Haemophilus
      through sequential heme-iron deplete and heme-iron replete media to determine the
      effect of transient depletion of internal stores of heme-iron on multiple
      pathogenic phenotypes. We observed that prior heme-iron restriction potentiates
      biofilm changes for at least 72 hours that include increased peak height and
      architectural complexity as compared to biofilms initiated from heme-iron replete
      bacteria, suggesting a mechanism for epigenetic responses that participate in the
      changes observed. Additionally, in a co-infection model for human otitis media,
      heme-iron restricted Haemophilus, although accounting for only 10% of the
      inoculum (90% heme-iron replete), represented up to 99% of the organisms
      recovered at 4 days. These data indicate that fluctuations in heme-iron
      availability promote a survival advantage during disease. Filamentation mediated
      by a SulA-related ortholog was required for optimal biofilm peak height and
      persistence during experimental otitis media. Moreover, severity of disease in
      response to heme-iron restricted Haemophilus was reduced as evidenced by lack of
      mucosal destruction, decreased erythema, hemorrhagic foci and vasodilatation.
      Transient restriction of heme-iron also promoted productive invasion events
      leading to the development of intracellular bacterial communities. Taken
      together, these data suggest that nutritional immunity, may, in fact, foster long
      term phenotypic changes that better equip bacteria for survival at infectious
      sites. 

PMID- 24130501
TI  - Identification of trans-sialidases as a common mediator of endothelial cell
      activation by African trypanosomes.
AB  - Understanding African Trypanosomiasis (AT) host-pathogen interaction is the key
      to an "anti-disease vaccine", a novel strategy to control AT. Here we provide a
      better insight into this poorly described interaction by characterizing the
      activation of a panel of endothelial cells by bloodstream forms of four African
      trypanosome species, known to interact with host endothelium. T. congolense, T.
      vivax, and T. b. gambiense activated the endothelial NF-kappaB pathway, but
      interestingly, not T. b. brucei. The parasitic TS (trans-sialidases) mediated
      this NF-kappaB activation, remarkably via their lectin-like domain and induced
      production of pro-inflammatory molecules not only in vitro but also in vivo,
      suggesting a considerable impact on pathogenesis. For the first time, TS activity
      was identified in T. b. gambiense BSF which distinguishes it from the subspecies
      T. b. brucei. The corresponding TS were characterized and shown to activate
      endothelial cells, suggesting that TS represent a common mediator of endothelium
      activation among trypanosome species with divergent physiopathologies. 

PMID- 24130502
TI  - Cooperation between RUNX1-ETO9a and novel transcriptional partner KLF6 in
      upregulation of Alox5 in acute myeloid leukemia.
AB  - Fusion protein RUNX1-ETO (AML1-ETO, RUNX1-RUNX1T1) is expressed as the result of
      the 8q22;21q22 translocation [t(8;21)], which is one of the most common
      chromosomal abnormalities found in acute myeloid leukemia. RUNX1-ETO is thought
      to promote leukemia development through the aberrant regulation of RUNX1 (AML1)
      target genes. Repression of these genes occurs via the recruitment of the
      corepressors N-COR and SMRT due to their interaction with ETO. Mechanisms of
      RUNX1-ETO target gene upregulation remain less well understood. Here we show that
      RUNX1-ETO9a, the leukemogenic alternatively spliced transcript expressed from
      t(8;21), upregulates target gene Alox5, which is a gene critically required for
      the promotion of chronic myeloid leukemia development by BCR-ABL. Loss of Alox5
      expression reduces activity of RUNX1-ETO9a, MLL-AF9 and PML-RARalpha in vitro.
      However, Alox5 is not essential for the induction of leukemia by RUNX1-ETO9a in
      vivo. Finally, we demonstrate that the upregulation of Alox5 by RUNX1-ETO9a
      occurs via the C2H2 zinc finger transcription factor KLF6, a protein required for
      early hematopoiesis and yolk sac development. Furthermore, KLF6 is specifically
      upregulated by RUNX1-ETO in human leukemia cells. This identifies KLF6 as a novel
      mediator of t(8;21) target gene regulation, providing a new mechanism for RUNX1
      ETO transcriptional control.

PMID- 24130503
TI  - Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain
      injury in stroke.
AB  - During ischemic stroke, occlusion of the cerebrovasculature causes neuronal cell
      death (infarction), but naturally occurring genetic factors modulating infarction
      have been difficult to identify in human populations. In a surgically induced
      mouse model of ischemic stroke, we have previously mapped Civq1 to distal
      chromosome 7 as a quantitative trait locus determining infarct volume. In this
      study, genome-wide association mapping using 32 inbred mouse strains and an
      additional linkage scan for infarct volume confirmed that the size of the infarct
      is determined by ancestral alleles of the causative gene(s). The genetically
      isolated Civq1 locus in reciprocal recombinant congenic mice refined the critical
      interval and demonstrated that infarct size is determined by both vascular
      (collateral vessel anatomy) and non-vascular (neuroprotection) effects. Through
      the use of interval-specific SNP haplotype analysis, we further refined the Civq1
      locus and identified integrin alpha L (Itgal) as one of the causative genes for
      Civq1. Itgal is the only gene that exhibits both strain-specific amino acid
      substitutions and expression differences. Coding SNPs, a 5-bp insertion in exon
      30b, and increased mRNA and protein expression of a splice variant of the gene
      (Itgal-003, ENSMUST00000120857), all segregate with infarct volume. Mice lacking
      Itgal show increased neuronal cell death in both ex vivo brain slice and in vivo
      focal cerebral ischemia. Our data demonstrate that sequence variation in Itgal
      modulates ischemic brain injury, and that infarct volume is determined by both
      vascular and non-vascular mechanisms. 

PMID- 24130504
TI  - Rad52 sumoylation prevents the toxicity of unproductive Rad51 filaments
      independently of the anti-recombinase Srs2.
AB  - The budding yeast Srs2 is the archetype of helicases that regulate several
      aspects of homologous recombination (HR) to maintain genomic stability. Srs2
      inhibits HR at replication forks and prevents high frequencies of crossing-over.
      Additionally, sensitivity to DNA damage and synthetic lethality with replication
      and recombination mutants are phenotypes that can only be attributed to another
      role of Srs2: the elimination of lethal intermediates formed by recombination
      proteins. To shed light on these intermediates, we searched for mutations that
      bypass the requirement of Srs2 in DNA repair without affecting HR. Remarkably, we
      isolated rad52-L264P, a novel allele of RAD52, a gene that encodes one of the
      most central recombination proteins in yeast. This mutation suppresses a broad
      spectrum of srs2Delta phenotypes in haploid cells, such as UV and gamma-ray
      sensitivities as well as synthetic lethality with replication and recombination
      mutants, while it does not significantly affect Rad52 functions in HR and DNA
      repair. Extensive analysis of the genetic interactions between rad52-L264P and
      srs2Delta shows that rad52-L264P bypasses the requirement for Srs2 specifically
      for the prevention of toxic Rad51 filaments. Conversely, this Rad52 mutant cannot
      restore viability of srs2Delta cells that accumulate intertwined recombination
      intermediates which are normally processed by Srs2 post-synaptic functions. The
      avoidance of toxic Rad51 filaments by Rad52-L264P can be explained by a
      modification of its Rad51 filament mediator activity, as indicated by Chromatin
      immunoprecipitation and biochemical analysis. Remarkably, sensitivity to DNA
      damage of srs2Delta cells can also be overcome by stimulating Rad52 sumoylation
      through overexpression of the sumo-ligase SIZ2, or by replacing Rad52 by a Rad52
      SUMO fusion protein. We propose that, like the rad52-L264P mutation, sumoylation
      modifies Rad52 activity thereby changing the properties of Rad51 filaments. This
      conclusion is strengthened by the finding that Rad52 is often associated with
      complete Rad51 filaments in vitro. 

PMID- 24130505
TI  - Reverse PCA, a systematic approach for identifying genes important for the
      physical interaction between protein pairs.
AB  - Protein-protein interactions (PPIs) are of central importance for many areas of
      biological research. Several complementary high-throughput technologies have been
      developed to study PPIs. The wealth of information that emerged from these
      technologies led to the first maps of the protein interactomes of several model
      organisms. Many changes can occur in protein complexes as a result of genetic and
      biochemical perturbations. In the absence of a suitable assay, such changes are
      difficult to identify, and thus have been poorly characterized. In this study, we
      present a novel genetic approach (termed "reverse PCA") that allows the
      identification of genes whose products are required for the physical interaction
      between two given proteins. Our assay starts with a yeast strain in which the
      interaction between two proteins of interest can be detected by resistance to the
      drug, methotrexate, in the context of the protein-fragment complementation assay
      (PCA). Using synthetic genetic array (SGA) technology, we can systematically
      screen mutant libraries of the yeast Saccharomyces cerevisiae to identify those
      mutations that disrupt the physical interaction of interest. We were able to
      successfully validate this novel approach by identifying mutants that dissociate
      the conserved interaction between Cia2 and Mms19, two proteins involved in Iron
      Sulfur protein biogenesis and genome stability. This method will facilitate the
      study of protein structure-function relationships, and may help in elucidating
      the mechanisms that regulate PPIs. 

PMID- 24130506
TI  - A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR
      mediated non-canonical steroid action to cAMP signaling in the adult brain.
AB  - The biological actions of steroid hormones are mediated primarily by their
      cognate nuclear receptors, which serve as steroid-dependent transcription
      factors. However, steroids can also execute their functions by modulating
      intracellular signaling cascades rapidly and independently of transcriptional
      regulation. Despite the potential significance of such "non-genomic" steroid
      actions, their biological roles and the underlying molecular mechanisms are not
      well understood, particularly with regard to their effects on behavioral
      regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy
      ecdysone (20E), which plays a variety of pivotal roles during development via the
      nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled
      receptor for ecdysteroids, is involved in activity- and experience-dependent
      plasticity of the adult central nervous system. Remarkably, a courtship memory
      defect in rutabaga (Ca2+/calmodulin-responsive adenylate cyclase) mutants was
      rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in
      dunce (cAMP-specific phosphodiestrase) mutants was counteracted when a loss-of
      function DopEcR mutation was introduced. A memory defect caused by suppressing
      dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone
      signaling, and rescue and phenocopy experiments revealed that the mushroom body
      (MB)--a brain region central to learning and memory in Drosophila--is critical
      for the DopEcR-dependent processing of courtship memory. Consistent with this
      finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP
      levels in the MB. Our multidisciplinary approach demonstrates that DopEcR
      mediates the non-canonical actions of 20E and rapidly modulates adult conditioned
      behavior through cAMP signaling, which is universally important for neural
      plasticity. This study provides novel insights into non-genomic actions of
      steroids, and opens a new avenue for genetic investigation into an
      underappreciated mechanism critical to behavioral control by steroids.

PMID- 24130507
TI  - Inhibition of the mitotic exit network in response to damaged telomeres.
AB  - When chromosomal DNA is damaged, progression through the cell cycle is halted to
      provide the cells with time to repair the genetic material before it is
      distributed between the mother and daughter cells. In Saccharomyces cerevisiae,
      this cell cycle arrest occurs at the G2/M transition. However, it is also
      necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor
      of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and
      Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned
      and the spindle position checkpoint is activated has been extensively studied,
      the mechanism by which these proteins prevent MEN function after DNA damage is
      still unclear. Here, we propose that the inhibition of the MEN is specifically
      required when telomeres are damaged but it is not necessary to face all types of
      chromosomal DNA damage, which is in agreement with previous data in mammals
      suggesting the existence of a putative telomere-specific DNA damage response that
      inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN
      inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of
      Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of
      this kinase in regulating cell cycle progression. 

PMID- 24130508
TI  - Multiple bHLH proteins form heterodimers to mediate CRY2-dependent regulation of
      flowering-time in Arabidopsis.
AB  - Arabidopsis thaliana cryptochrome 2 (CRY2) mediates light control of flowering
      time. CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response
      to blue light to activate the transcription of FT (Flowering Locus T). In vitro,
      CIB1 binds to the canonical E-box (CACGTG, also referred to as G-box) with much
      higher affinity than its interaction with non-canonical E-box (CANNTG) DNA
      sequences. However, in vivo, CIB1 binds to the chromatin region of the FT
      promoter, which only contains the non-canonical E-box sequences. Here, we show
      that CRY2 also interacts with at least CIB5, in response to blue light, but not
      in darkness or in response to other wavelengths of light. Our genetic analysis
      demonstrates that CIB1, CIB2, CIB4, and CIB5 act redundantly to activate the
      transcription of FT and that they are positive regulators of CRY2 mediated
      flowering. More importantly, CIB1 and other CIBs proteins form heterodimers, and
      some of the heterodimers have a higher binding affinity than the CIB homodimers
      to the non-canonical E-box in the in vitro DNA-binding assays. This result
      explains why in vitro CIB1 and other CIBs bind to the canonical E-box (G-box)
      with a higher affinity, whereas they are all associated with the non-canonical E
      boxes at the FT promoter in vivo. Consistent with the hypothesis that different
      CIB proteins play similar roles in the CRY2-midiated blue light signaling, the
      expression of CIB proteins is regulated specifically by blue light. Our study
      demonstrates that CIBs function redundantly in regulating CRY2-dependent
      flowering, and that different CIBs form heterodimers to interact with the non
      canonical E-box DNA in vivo. 

PMID- 24130509
TI  - Dominant role of nucleotide substitution in the diversification of serotype 3
      pneumococci over decades and during a single infection.
AB  - Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease
      associated with high mortality rates relative to other pneumococci. Phylogenetic
      analysis of a complete reference genome and 81 draft sequences from clonal
      complex 180, the predominant serotype 3 clone in much of the world, found most
      sampled isolates belonged to a clade affected by few diversifying recombinations.
      However, other isolates indicate significant genetic variation has accumulated
      over the clonal complex's entire history. Two closely related genomes, one from
      the blood and another from the cerebrospinal fluid, were obtained from a patient
      with meningitis. The pair differed in their behaviour in a mouse model of disease
      and in their susceptibility to antimicrobials, with at least some of these
      changes attributable to a mutation that up-regulated the patAB efflux pump. This
      indicates clinically important phenotypic variation can accumulate rapidly
      through small alterations to the genotype. 

PMID- 24130511
TI  - Function and evolution of DNA methylation in Nasonia vitripennis.
AB  - The parasitoid wasp Nasonia vitripennis is an emerging genetic model for
      functional analysis of DNA methylation. Here, we characterize genome-wide
      methylation at a base-pair resolution, and compare these results to gene
      expression across five developmental stages and to methylation patterns reported
      in other insects. An accurate assessment of DNA methylation across the genome is
      accomplished using bisulfite sequencing of adult females from a highly inbred
      line. One-third of genes show extensive methylation over the gene body, yet
      methylated DNA is not found in non-coding regions and rarely in transposons.
      Methylated genes occur in small clusters across the genome. Methylation
      demarcates exon-intron boundaries, with elevated levels over exons, primarily in
      the 5' regions of genes. It is also elevated near the sites of translational
      initiation and termination, with reduced levels in 5' and 3' UTRs. Methylated
      genes have higher median expression levels and lower expression variation across
      development stages than non-methylated genes. There is no difference in frequency
      of differential splicing between methylated and non-methylated genes, and as yet
      no established role for methylation in regulating alternative splicing in
      Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation
      status across long evolutionary time scales. Nasonia methylated genes are more
      likely to be conserved in insects, but even those that are not conserved show
      broader expression across development than comparable non-methylated genes.
      Finally, examination of duplicated genes shows that those paralogs that have lost
      methylation in the Nasonia lineage following gene duplication evolve more
      rapidly, show decreased median expression levels, and increased specialization in
      expression across development. Methylation of Nasonia genes signals constitutive
      transcription across developmental stages, whereas non-methylated genes show more
      dynamic developmental expression patterns. We speculate that loss of methylation
      may result in increased developmental specialization in evolution and acquisition
      of methylation may lead to broader constitutive expression. 

PMID- 24130513
TI  - Health effects associated with foods characteristic of the Nordic diet: a
      systematic literature review.
AB  - BACKGROUND: In preparing the fifth edition of the Nordic Nutrition
      Recommendations (NNR), the scientific basis of specific food-based dietary
      guidelines (FBDG) was evaluated. OBJECTIVE: A systematic review (SR) was
      conducted to update the NNR evidence based on the association between the
      consumption of potatoes, berries, whole grains, milk and milk products, and red
      and processed meat, and the risk of major diet-related chronic diseases. DESIGN:
      The SR was based on predefined research questions and eligibility criteria for
      independent duplicate study selection, data extraction, and assessment of
      methodological quality and applicability. We considered scientific data from
      prospective observational studies and intervention studies, published since year
      2000, targeting the general adult population. Studies of meat and iron status
      included children, adolescents, and women of childbearing age. RESULTS: Based on
      7,282 abstracts, 57 studies met the quality criteria and were evidence graded.
      The data were too limited to draw any conclusions regarding: red and processed
      meat intake in relation to cardiovascular disease (CVD) and iron status; potatoes
      and berries regarding any study outcomes; and dairy consumption in relation to
      risk of breast cancer and CVD. However, dairy consumption seemed unlikely to
      increase CVD risk (moderate-grade evidence). There was probable evidence
      (moderate-grade) for whole grains protecting against type 2 diabetes and CVD, and
      suggestive evidence (low-grade) for colorectal cancer and for dairy consumption
      being associated with decreased risk of type 2 diabetes and increased risk of
      prostate cancer. The WCRF/AICR concludes that red and processed meat is a
      convincing cause of colorectal cancer. CONCLUSIONS: Probable (moderate) evidence
      was only observed for whole grains protecting against type 2 diabetes and CVD. We
      identified a clear need for high-quality nutritional epidemiological and
      intervention studies and for studies of foods of the Nordic diet.

PMID- 24130510
TI  - Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10
      expression.
AB  - Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from
      patients with systemic lupus erythematosus (SLE) correlating with disease
      activity. The established association of IL10 with SLE and other autoimmune
      diseases led us to fine map causal variant(s) and to explore underlying
      mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including
      IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects
      from four ancestries. The previously reported IL10 variant, rs3024505 located at
      1 kb downstream of IL10, exhibited the strongest association signal and was
      confirmed for association with SLE in European American (EA) (P = 2.7*10-8, OR =
      1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset
      identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605,
      rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10,
      respectively), and SLE-risk alleles of these SNPs were dose-dependently
      associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10
      protein in SLE patients and controls. Using nuclear extracts of peripheral blood
      cells from SLE patients for electrophoretic mobility shift assays, we identified
      specific binding of transcription factor Elk-1 to oligodeoxynucleotides
      containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most
      likely causal variant regulating IL10 expression. Elk-1 is known to be activated
      by phosphorylation and nuclear localization to induce transcription. Of interest,
      phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs
      appeared to increase with disease activity. Co-expression levels of p-Elk-1 and
      IL-10 were elevated in SLE T, B cells and monocytes, associated with increased
      disease activity in SLE B cells, and were best downregulated by ERK inhibitor.
      Taken together, our data suggest that preferential binding of activated Elk-1 to
      the IL10 rs3122605-G allele upregulates IL10 expression and confers increased
      risk for SLE in European Americans.

PMID- 24130514
TI  - Heads for learning, tails for memory: reward, reinforcement and a role of
      dopamine in determining behavioral relevance across multiple timescales.
AB  - Dopamine has long been tightly associated with aspects of reinforcement learning
      and motivation in simple situations where there are a limited number of stimuli
      to guide behavior and constrained range of outcomes. In naturalistic situations,
      however, there are many potential cues and foraging strategies that could be
      adopted, and it is critical that animals determine what might be behaviorally
      relevant in such complex environments. This requires not only detecting
      discrepancies with what they have recently experienced, but also identifying
      similarities with past experiences stored in memory. Here, we review what role
      dopamine might play in determining how and when to learn about the world, and how
      to develop choice policies appropriate to the situation faced. We discuss
      evidence that dopamine is shaped by motivation and memory and in turn shapes
      reward-based memory formation. In particular, we suggest that hippocampal
      striatal-dopamine networks may interact to determine how surprising the world is
      and to either inhibit or promote actions at time of behavioral uncertainty. 

PMID- 24130515
TI  - Unraveling the complex metabolic nature of astrocytes.
AB  - Since the initial description of astrocytes by neuroanatomists of the nineteenth
      century, a critical metabolic role for these cells has been suggested in the
      central nervous system. Nonetheless, it took several technological and conceptual
      advances over many years before we could start to understand how they fulfill
      such a role. One of the important and early recognized metabolic function of
      astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate.
      But the description of this initial property will be followed by several others
      including an implication in the supply of energetic substrates to neurons.
      Indeed, despite the fact that like most eukaryotic non-proliferative cells,
      astrocytes rely on oxidative metabolism for energy production, they exhibit a
      prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature
      was found to be modulated by glutamatergic activity constituting the initial step
      of the neurometabolic coupling mechanism. Several approaches, including
      biochemical measurements in cultured cells, genetic screening, dynamic cell
      imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have
      provided further insights into the intrinsic characteristics giving rise to these
      key features of astrocytes. This review will provide an account of the different
      results obtained over several decades that contributed to unravel the complex
      metabolic nature of astrocytes that make this cell type unique. 

PMID- 24130516
TI  - Prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure and serotonin
      transporter promoter genotype (SLC6A4) influence executive functions at 6 years
      of age.
AB  - Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants and
      maternal depression may affect prefrontal cognitive skills (executive functions;
      EFs) including self-control, working memory and cognitive flexibility. We
      examined long-term effects of prenatal SRI exposure on EFs to determine whether
      effects are moderated by maternal mood and/or genetic variations in SLC6A4 (a
      gene that codes for the serotonin transporter [5-HTT] central to the regulation
      of synaptic serotonin levels and behavior). Children who were exposed to SRIs
      prenatally (SRI-exposed N = 26) and non-exposed (N = 38) were studied at age 6
      years (M = 6.3; SD = 0.5) using the Hearts & Flowers task (H&F) to assess EFs.
      Maternal mood was measured during pregnancy (3rd trimester) and when the child
      was age 6 years (Hamilton Depression Scale). Parent reports of child behavior
      were also obtained (MacArthur Health & Behavior Questionnaire). Parents of
      prenatally SRI-exposed children reported fewer child externalizing and
      inattentive (ADHD) behaviors. Generalized estimate equation modeling showed a
      significant 3-way interaction between prenatal SRI exposure, SLC6A4 variant, and
      maternal mood at the 6-year time-point on H&F accuracy. For prenatally SRI
      exposed children, regardless of maternal mood, the H&F accuracy of children with
      reduced 5HTT expression (a short [S] allele) remained stable. Even with
      increasing maternal depressive symptoms (though all below clinical threshold),
      EFs of children with at least one short allele were comparable to children with
      the same genotype whose mothers reported few if any depressive symptoms-in this
      sense they showed resilience. Children with two long (L) alleles were more
      sensitive to context. When their mothers had few depressive symptoms, LL children
      showed extremely good EF performance-better than any other group. When their
      mothers reported more depressive symptoms, LL children's EF performance was worse
      than that of any other group. In the face of a mother with a more depressed mood,
      EFs were best preserved in children prenatally exposed to SRIs and with at least
      one short SLC6A4 allele. Yet, prenatally-exposed LL children hold out promise of
      possibly superior EF if their mother's mood remains euthymic or improves. 

PMID- 24130517
TI  - Dopamine signaling in reward-related behaviors.
AB  - Dopamine (DA) regulates emotional and motivational behavior through the
      mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have
      been found to modify behavioral responses to various environmental stimuli
      associated with reward behaviors. Psychostimulants, drugs of abuse, and natural
      reward such as food can cause substantial synaptic modifications to the
      mesolimbic DA system. Recent studies using optogenetics and DREADDs, together
      with neuron-specific or circuit-specific genetic manipulations have improved our
      understanding of DA signaling in the reward circuit, and provided a means to
      identify the neural substrates of complex behaviors such as drug addiction and
      eating disorders. This review focuses on the role of the DA system in drug
      addiction and food motivation, with an overview of the role of D1 and D2
      receptors in the control of reward-associated behaviors. 

PMID- 24130518
TI  - Distributed cerebellar plasticity implements adaptable gain control in a
      manipulation task: a closed-loop robotic simulation.
AB  - Adaptable gain regulation is at the core of the forward controller operation
      performed by the cerebro-cerebellar loops and it allows the intensity of motor
      acts to be finely tuned in a predictive manner. In order to learn and store
      information about body-object dynamics and to generate an internal model of
      movement, the cerebellum is thought to employ long-term synaptic plasticity. LTD
      at the PF-PC synapse has classically been assumed to subserve this function
      (Marr, 1969). However, this plasticity alone cannot account for the broad dynamic
      ranges and time scales of cerebellar adaptation. We therefore tested the role of
      plasticity distributed over multiple synaptic sites (Hansel et al., 2001; Gao et
      al., 2012) by generating an analog cerebellar model embedded into a control loop
      connected to a robotic simulator. The robot used a three-joint arm and performed
      repetitive fast manipulations with different masses along an 8-shape trajectory.
      In accordance with biological evidence, the cerebellum model was endowed with
      both LTD and LTP at the PF-PC, MF-DCN and PC-DCN synapses. This resulted in a
      network scheme whose effectiveness was extended considerably compared to one
      including just PF-PC synaptic plasticity. Indeed, the system including
      distributed plasticity reliably self-adapted to manipulate different masses and
      to learn the arm-object dynamics over a time course that included fast learning
      and consolidation, along the lines of what has been observed in behavioral tests.
      In particular, PF-PC plasticity operated as a time correlator between the actual
      input state and the system error, while MF-DCN and PC-DCN plasticity played a key
      role in generating the gain controller. This model suggests that distributed
      synaptic plasticity allows generation of the complex learning properties of the
      cerebellum. The incorporation of further plasticity mechanisms and of spiking
      signal processing will allow this concept to be extended in a more realistic
      computational scenario. 

PMID- 24130520
TI  - Viral vector-mediated selective and reversible blockade of the pathway for visual
      orienting in mice.
AB  - Recently, by using a combination of two viral vectors, we developed a technique
      for pathway-selective and reversible synaptic transmission blockade, and
      successfully induced a behavioral deficit of dexterous hand movements in macaque
      monkeys by affecting a population of spinal interneurons. To explore the capacity
      of this technique to work in other pathways and species, and to obtain
      fundamental methodological information, we tried to block the crossed tecto
      reticular pathway, which is known to control orienting responses to visual
      targets, in mice. A neuron-specific retrograde gene transfer vector with the gene
      encoding enhanced tetanus neurotoxin (eTeNT) tagged with enhanced green
      fluorescent protein (EGFP) under the control of a tetracycline responsive element
      was injected into the left medial pontine reticular formation. 7-17 days later,
      an adeno-associated viral vector with a highly efficient Tet-ON sequence,
      rtTAV16, was injected into the right superior colliculus. 5-9 weeks later, the
      daily administration of doxycycline (Dox) was initiated. Visual orienting
      responses toward the left side were impaired 1-4 days after Dox administration.
      Anti-GFP immunohistochemistry revealed that a number of neurons in the
      intermediate and deep layers of the right superior colliculus were positively
      stained, indicating eTeNT expression. After the termination of Dox
      administration, the anti-GFP staining returned to the baseline level within 28
      days. A second round of Dox administration, starting from 28 days after the
      termination of the first Dox administration, resulted in the reappearance of the
      behavioral impairment. These findings showed that pathway-selective and
      reversible blockade of synaptic transmission also causes behavioral effects in
      rodents, and that the crossed tecto-reticular pathway clearly controls visual
      orienting behaviors. 

PMID- 24130519
TI  - Induction and modulation of persistent activity in a layer V PFC microcircuit
      model.
AB  - Working memory refers to the temporary storage of information and is strongly
      associated with the prefrontal cortex (PFC). Persistent activity of cortical
      neurons, namely the activity that persists beyond the stimulus presentation, is
      considered the cellular correlate of working memory. Although past studies
      suggested that this type of activity is characteristic of large scale networks,
      recent experimental evidence imply that small, tightly interconnected clusters of
      neurons in the cortex may support similar functionalities. However, very little
      is known about the biophysical mechanisms giving rise to persistent activity in
      small-sized microcircuits in the PFC. Here, we present a detailed biophysically
      yet morphologically simplified-microcircuit model of layer V PFC neurons that
      incorporates connectivity constraints and is validated against a multitude of
      experimental data. We show that (a) a small-sized network can exhibit persistent
      activity under realistic stimulus conditions. (b) Its emergence depends strongly
      on the interplay of dADP, NMDA, and GABAB currents. (c) Although increases in
      stimulus duration increase the probability of persistent activity induction,
      variability in the stimulus firing frequency does not consistently influence it.
      (d) Modulation of ionic conductances (I h , I D , I sAHP, I caL, I caN, I caR)
      differentially controls persistent activity properties in a location dependent
      manner. These findings suggest that modulation of the microcircuit's firing
      characteristics is achieved primarily through changes in its intrinsic mechanism
      makeup, supporting the hypothesis of multiple bi-stable units in the PFC.
      Overall, the model generates a number of experimentally testable predictions that
      may lead to a better understanding of the biophysical mechanisms of persistent
      activity induction and modulation in the PFC. 

PMID- 24130521
TI  - Intravital imaging of hair-cell development and regeneration in the zebrafish.
AB  - Direct videomicroscopic visualization of organ formation and regeneration in toto
      is a powerful strategy to study cellular processes that often cannot be
      replicated in vitro. Intravital imaging aims at quantifying changes in tissue
      architecture or subcellular organization over time during organ development,
      regeneration or degeneration. A general feature of this approach is its reliance
      on the optical isolation of defined cell types in the whole animals by transgenic
      expression of fluorescent markers. Here we describe a simple and robust method to
      analyze sensory hair-cell development and regeneration in the zebrafish lateral
      line by high-resolution intravital imaging using laser-scanning confocal
      microscopy (LSCM) and selective plane illumination microscopy (SPIM). The main
      advantage of studying hair-cell regeneration in the lateral line is that it
      occurs throughout the life of the animal, which allows its study in the most
      natural context. We detail protocols to achieve continuous videomicroscopy for up
      to 68 hours, enabling direct observation of cellular behavior, which can provide
      a sensitive assay for the quantitative classification of cellular phenotypes and
      cell-lineage reconstruction. Modifications to this protocol should facilitate
      pharmacogenetic assays to identify or validate otoprotective or reparative drugs
      for future clinical strategies aimed at preserving aural function in humans. 

PMID- 24130522
TI  - The role of the anterior, mediodorsal, and parafascicular thalamus in
      instrumental conditioning.
AB  - The traditional animal model of instrumental behavior has focused almost
      exclusively on structures within the cortico-striatal network and ignored the
      contributions of various thalamic nuclei despite large and specific connections
      with each of these structures. One possible reason for this is that the thalamus
      has been conventionally viewed as a mediator of general processes, such as
      attention, arousal and movement, that are not easily separated from more
      cognitive aspects of instrumental behavior. Recent research has, however, begun
      to separate these roles. Here we review the role of three thalamic nuclei in
      instrumental conditioning: the anterior thalamic nuclei (ANT), the mediodorsal
      (MD), and parafascicular thalamic nuclei (PF). Early research suggested that ANT
      might regulate aspects of instrumental behavior but, on review, we suggest that
      the types of tasks used in these studies were more likely to recruit Pavlovian
      processes. Indeed lesions of ANT have been found to have no effect on performance
      in instrumental free-operant tasks. By contrast the mediodorsal thalamus (MD) has
      been found to play a specific and important role in the acquisition of goal
      directed action. We propose this role is related to its connections with
      prelimbic cortex (PL) and present new data that directly implicates this circuit
      in the acquisition of goal-directed actions. Finally we review evidence
      suggesting the PF, although not critical for the acquisition or performance of
      instrumental actions, plays a specific role in regulating action flexibility. 

PMID- 24130523
TI  - Stress effects on framed decisions: there are differences for gains and losses.
AB  - Recent studies have shown that acute stress can lead to riskier decision making.
      Yet, the underlying mechanisms of the stress effects on decisions under risk
      remain poorly understood. To gain a better understanding of decision-making
      processes and potential strategy application under stress, we investigated
      decision making in pure gain and loss domains with unequal expected values (EVs)
      across alternatives. We conducted an experimental study with a 2 * 2 design
      (stress vs. no stress and gain domain vs. loss domain). The Trier Social Stress
      Test (TSST) was utilized to induce acute stress. Controls performed the placebo
      TSST (p-TSST). To validate the stress response we measured salivary cortisol and
      alpha-amylase concentrations. We used a modified version of the Game of Dice Task
      (GDT) to assess decision-making performance in a gain and a loss domain. Results
      showed that non-stressed participants made less risky decisions in the gain
      domain compared to those of the loss domain. This behavior is in accordance with
      previous studies and indicates the stability of the framing effect in even more
      complex tasks with changing EVs across alternatives. Stress did not alter risk
      taking behavior in the gain domain. Yet, in the loss domain stressed participants
      made less risky decisions compared to controls. Additionally, the data support
      earlier findings of longer reaction times in loss compared to gain domains due to
      higher cognitive effort for loss-framed decisions. It is discussed that stress
      may lead to reduced amygdala activation, which has been found to reduce riskier
      decisions in a loss domain. With respect to earlier results of riskier decisions
      in tasks that unite both gain and loss domains, it is discussed whether stress
      leads to a stronger evaluation of high gains and a neglect of losses. 

PMID- 24130526
TI  - Challenges for the understanding of the dynamics of social coordination.
AB  - The way people interact can be examined by looking at the way they move relative
      to each other. Seeking the principles behind those interactions have consequences
      potentially related to any type of interpersonal function, far beyond the so
      called "motor" processes typically associated with the study of movements, be it
      perceptive, cognitive, affective, pragmatic, or epistemic. Here, we present the
      way the framework of coordination dynamics define and addresses the interactive
      actions in a dyad. We first introduce the basics of pattern formation as the
      roots of the theoretical approach of coordination dynamics, and then the way this
      framework may contribute to establish a solution to classify behaviors.
      Thereafter we review promising empirical results on the dynamics of interpersonal
      coordination, and finally discuss were to go next to decipher the way the
      coordination between two people and the way each individual contribute may be
      disentangled. 

PMID- 24130524
TI  - Cortical plasticity within and across lifetimes: how can development inform us
      about phenotypic transformations?
AB  - The neocortex is the part of the mammalian brain that is involved in perception,
      cognition, and volitional motor control. It is a highly dynamic structure that is
      dramatically altered within the lifetime of an animal and in different lineages
      throughout the course of evolution. These alterations account for the remarkable
      variations in behavior that species exhibit. Of particular interest is how these
      cortical phenotypes change within the lifetime of the individual and eventually
      evolve in species over time. Because we cannot study the evolution of the
      neocortex directly we use comparative analysis to appreciate the types of changes
      that have been made to the neocortex and the similarities that exist across taxa.
      Developmental studies inform us about how these phenotypic transitions may arise
      by alterations in developmental cascades or changes in the physical environment
      in which the brain develops. Both genes and the sensory environment contribute to
      aspects of the phenotype and similar features, such as the size of a cortical
      field, can be altered in a variety of ways. Although both genes and the laws of
      physics place constraints on the evolution of the neocortex, mammals have evolved
      a number of mechanisms that allow them to loosen these constraints and often
      alter the course of their own evolution. 

PMID- 24130525
TI  - Emotional modulation of the attentional blink and the relation to interpersonal
      reactivity.
AB  - The extent of the attentional blink effect on detection rates in rapid serial
      visual presentations is modulated by the emotionality of the stimuli. Emotionally
      salient stimuli are detected more often, even if presented in the attentional
      blink period, and elicit an enlarged P3 response, which has been interpreted as
      enhanced consolidation. This effect correlates with individual differences in
      trait affectivity such as anxiety or dysphoria. Here, we ask if it is also
      related to the capacity to detect emotions in others, i.e., to interpersonal
      social traits. We therefore presented emotional and neutral images depicting
      social scenes as targets in an attentional blink design and measured detection
      rates and event-related potentials. In addition, we recorded self-reports of
      empathy as measured by the Interpersonal Reactivity Index. The results show
      enhanced performance for emotional stimuli and increased P3 amplitudes, which
      correlated with individual differences in empathy. The data suggest that self
      reported empathy goes along with enhanced processing of emotion in social
      stimuli, even under stimulus conditions that are suboptimal for conscious target
      detection. 

PMID- 24130527
TI  - A long-lasting wireless stimulator for small mammals.
AB  - The chronic effects of electrical stimulation in unrestrained awake rodents are
      best studied with a wireless neural stimulator that can operate unsupervised for
      several weeks or more. A robust, inexpensive, easily built, cranially implantable
      stimulator was developed to explore the restorative effects of brainstem
      stimulation after neurotrauma. Its connectorless electrodes directly protrude
      from a cuboid epoxy capsule containing all circuitry and power sources. This
      physical arrangement prevents fluid leaks or wire breakage and also simplifies
      and speeds implantation. Constant-current pulses of high compliance (34 volts)
      are delivered from a step-up voltage regulator under microprocessor control. A
      slowly pulsed magnetic field controls activation state and stimulation
      parameters. Program status is signaled to a remote reader by interval-modulated
      infrared pulses. Capsule size is limited by the two batteries. Silver oxide
      batteries rated at 8 mA-h were used routinely in 8 mm wide, 15 mm long and 4 mm
      high capsules. Devices of smaller contact area (5 by 12 mm) but taller (6 mm)
      were created for mice. Microstimulation of the rat's raphe nuclei with
      intermittent 5-min (50% duty cycle) trains of 30 MUA, 1 ms pulses at 8 or 24 Hz
      frequency during 12 daylight hours lasted 21.1 days +/-0.8 (mean +/- standard
      error, Kaplan-Meir censored estimate, n = 128). Extended lifetimes (>6 weeks, no
      failures, n = 16) were achieved with larger batteries (44 mA-h) in longer (18
      mm), taller (6 mm) capsules. The circuit and electrode design are versatile;
      simple modifications allowed durable constant-voltage stimulation of the rat's
      sciatic nerve through a cylindrical cathode from a subcutaneous pelvic capsule.
      Devices with these general features can address in small mammals many of the
      biological and technical questions arising neurosurgically with prolonged
      peripheral or deep brain stimulation. 

PMID- 24130528
TI  - Biomarker-based prediction of progression in MCI: Comparison of AD signature and
      hippocampal volume with spinal fluid amyloid-beta and tau.
AB  - OBJECTIVE: New diagnostic criteria for mild cognitive impairment (MCI) due to
      Alzheimer's disease (AD) have been developed using biomarkers aiming to establish
      whether the clinical syndrome is likely due to underlying AD. We investigated the
      utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF)
      biomarkers in predicting progression from amnesic MCI to dementia, testing the
      hypotheses that (1) markers of amyloid and neurodegeneration provide distinct and
      complementary prognostic information over different time intervals, and that (2)
      evidence of neurodegeneration in amyloid-negative MCI individuals would be useful
      prognostically. METHODS: Data were obtained from the ADNI-1 (Alzheimer's Disease
      Neuroimaging Initiative Phase 1) database on all individuals with a baseline
      diagnosis of MCI, baseline MRI and CSF data, and at least one follow-up visit.
      MRI data were processed using a published set of a priori regions of interest to
      derive a measure known as the ''AD signature,'' as well as hippocampal volume.
      The CSF biomarkers amyloid-beta, total tau, and phospho tau were also examined.
      We performed logistic regression analyses to identify the best baseline biomarker
      predictors of progression to dementia over 1 or 3 years, and Cox regression
      models to test the utility of these markers for predicting time-to-dementia.
      RESULTS: For prediction of dementia in MCI, the AD signature cortical thickness
      biomarker performed better than hippocampal volume. Although CSF tau measures
      were better than CSF amyloid-beta at predicting dementia within 1 year, the AD
      signature was better than all CSF measures at prediction over this relatively
      short-term interval. CSF amyloid-beta was superior to tau and AD signature at
      predicting dementia over 3 years. When CSF amyloid-beta was dichotomized using
      previously published cutoff values and treated as a categorical variable, a
      multivariate stepwise Cox regression model indicated that both the AD signature
      MRI marker and the categorical CSF amyloid-beta marker were useful in predicting
      time-to-event diagnosis of AD dementia. CONCLUSION: In amnesic MCI, short-term (1
      year) prognosis of progression to dementia relates strongly to baseline markers
      of neurodegeneration, with the AD signature MRI biomarker of cortical thickness
      performing the best among MRI and CSF markers studied here. Longer-term (3 year)
      prognosis in these individuals was better predicted by a marker indicative of
      brain amyloid. Prediction of time-to-event in a survival model was predicted by
      the combination of these biomarkers. These results provide further support for
      emerging models of the temporal relationship of pathophysiologic events in AD and
      demonstrate the utility of these biomarkers at the prodromal stage of the
      illness.

PMID- 24130529
TI  - Index of alpha/theta ratio of the electroencephalogram: a new marker for
      Alzheimer's disease.
AB  - OBJECTIVE: We evaluated quantitative EEG measures to determine a screening index
      to discriminate Alzheimer's disease (AD) patients from normal individuals.
      METHODS: Two groups of individuals older than 50 years, comprising a control
      group of 57 normal volunteers and a study group of 50 patients with probable AD,
      were compared. EEG recordings were obtained from subjects in a wake state with
      eyes closed at rest for 30 min. Logistic regression analysis was conducted.
      RESULTS: Spectral potentials of the alpha and theta bands were computed for all
      electrodes and the alpha/theta ratio calculated. Logistic regression of
      alpha/theta of the mean potential of the C3 and O1 electrodes was carried out. A
      formula was calculated to aid the diagnosis of AD yielding 76.4% sensitivity and
      84.6% specificity for AD with an area under the ROC curve of 0.92. CONCLUSION:
      Logistic regression of alpha/theta of the spectrum of the mean potential of EEG
      represents a good marker discriminating AD patients from normal controls.

PMID- 24130530
TI  - P2Y2 receptor knock-out mice display normal NaCl absorption in medullary thick
      ascending limb.
AB  - Local purinergic signals modulate renal tubular transport. Acute activation of
      renal epithelial P2 receptors causes inhibition of epithelial transport and thus,
      should favor increased water and salt excretion by the kidney. So far only a few
      studies have addressed the effects of extracellular nucleotides on ion transport
      in the thick ascending limb (TAL). In the medullary thick ascending limb (mTAL),
      basolateral P2X receptors markedly (~25%) inhibit NaCl absorption. Although this
      segment does express both apical and basolateral P2Y2 receptors, acute activation
      of the basolateral P2Y2 receptors had no apparent effect on transepithelial ion
      transport. Here we studied, if the absence of the P2Y2 receptor causes chronic
      alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated
      transepithelial transport rates. We used perfused mouse mTALs to electrically
      measure NaCl absorption in juvenile (<35 days) and adult (>35 days) male mice.
      Using microelectrodes, we determined the transepithelial voltage (Vte) and the
      transepithelial resistance (Rte) and thus, transepithelial NaCl absorption
      (equivalent short circuit current, I'sc). We find that mTALs from adult wild type
      (WT) mice have significantly lower NaCl absorption rates when compared to mTALs
      from juvenile WT mice. This could be attributed to significantly higher Rtevalues
      in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y2
      receptor knockout (KO) mice. In addition, adult P2Y2 receptor KO mTALs have
      significantly lower Vtevalues compared to the juvenile. No difference in absolute
      I'sc was observed when comparing mTALs from WT and KO mice. AVP stimulated the
      mTALs to similar increases of NaCl absorption irrespective of the absence of the
      P2Y2 receptor. No difference was observed in the medullary expression level of
      NKCC2 in between the genotypes. These data indicate that the lack of P2Y2
      receptors does not cause substantial differences in resting and AVP-stimulated
      NaCl absorption in mouse mTAL. 

PMID- 24130531
TI  - Alterations in muscle mass and contractile phenotype in response to unloading
      models: role of transcriptional/pretranslational mechanisms.
AB  - Skeletal muscle is the largest organ system in mammalian organisms providing
      postural control and movement patterns of varying intensity. Through evolution,
      skeletal muscle fibers have evolved into three phenotype clusters defined as a
      motor unit which consists of all muscle fibers innervated by a single motoneuron
      linking varying numbers of fibers of similar phenotype. This fundamental
      organization of the motor unit reflects the fact that there is a remarkable
      interdependence of gene regulation between the motoneurons and the muscle mainly
      via activity-dependent mechanisms. These fiber types can be classified via the
      primary type of myosin heavy chain (MHC) gene expressed in the motor unit. Four
      MHC gene encoded proteins have been identified in striated muscle: slow type I
      MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic
      contraction speed of the myofiber with the type I generating the slowest and IIb
      the fastest contractile speed. Over the last ~35 years, a large body of knowledge
      suggests that altered loading state cause both fiber atrophy/wasting and a slow
      to fast shift in the contractile phenotype in the target muscle(s). Hence, this
      review will examine findings from three different animal models of unloading: (1)
      space flight (SF), i.e., microgravity; (2) hindlimb suspension (HS), a procedure
      that chronically eliminates weight bearing of the lower limbs; and (3) spinal
      cord isolation (SI), a surgical procedure that eliminates neural activation of
      the motoneurons and associated muscles while maintaining neurotrophic motoneuron
      muscle connectivity. The collective findings demonstrate: (1) all three models
      show a similar pattern of fiber atrophy with differences mainly in the magnitude
      and kinetics of alteration; (2) transcriptional/pretranslational processes play a
      major role in both the atrophy process and phenotype shifts; and (3) signaling
      pathways impacting these alterations appear to be similar in each of the models
      investigated. 

PMID- 24130532
TI  - Systems approaches for synthetic biology: a pathway toward mammalian design.
AB  - We review methods of understanding cellular interactions through computation in
      order to guide the synthetic design of mammalian cells for translational
      applications, such as regenerative medicine and cancer therapies. In doing so, we
      argue that the challenges of engineering mammalian cells provide a prime
      opportunity to leverage advances in computational systems biology. We support
      this claim systematically, by addressing each of the principal challenges to
      existing synthetic bioengineering approaches-stochasticity, complexity, and scale
      with specific methods and paradigms in systems biology. Moreover, we characterize
      a key set of diverse computational techniques, including agent-based modeling,
      Bayesian network analysis, graph theory, and Gillespie simulations, with specific
      utility toward synthetic biology. Lastly, we examine the mammalian applications
      of synthetic biology for medicine and health, and how computational systems
      biology can aid in the continued development of these applications. 

PMID- 24130533
TI  - Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and
      hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF)
      effects.
AB  - In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M)
      elicits bronchoconstriction, but in healthy subjects exercise causes
      bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL)
      and increases its osmolarity. Hyperosmolar challenge of airway epithelium
      releases epithelium-derived relaxing factor (EpDRF), which relaxes the airway
      smooth muscle. This pathway could be involved in exercise-induced
      bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial
      function. We investigated the effects of osmolar challenge maneuvers on dispersed
      and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that
      EpDRF-mediated relaxation is associated with epithelial cell shrinkage.
      Enzymatically-dispersed cells shrank when challenged with >=10 mOsM added D-M,
      urea or NaCl with a concentration-dependence that mimics relaxation of the of
      isolated perfused tracheas (IPT). Cells shrank when incubated in isosmolar N
      methyl-D-glucamine (NMDG) chloride, Na gluconate (Glu), NMDG-Glu, K-Glu and
      K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not
      a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4'
      diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) inhibited relaxation of IPT to
      hyperosmolar challenge, but had little effect on shrinkage of dispersed cells.
      Confocal microscopy in tracheal segments showed that adherent epithelium is
      refractory to low hyperosmolar concentrations that induce dispersed cell
      shrinkage and relaxation of IPT. Except for gadolinium and erythro-9-(2-hydroxy-3
      nonyl)adenine (EHNA), actin and microtubule inhibitors and membrane
      permeabilizing agents did not affect on ion transport by adherent epithelium or
      shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT
      from cell shrinkage after hyperosmolar challenge of airway epithelium. 

PMID- 24130534
TI  - Efficacy of community treatments for schizophrenia and other psychotic disorders:
      a literature review.
AB  - BACKGROUND: In Chile, the clinical guidelines "for the treatment of people from
      first episode of schizophrenia" aim to support individuals with schizophrenia to
      live independently, establishment occupational goals, and gain an adequate
      quality of life and social interaction. This requires the implementation of a
      treatment model that integrates psychosocial and pharmacological dimensions.
      Community intervention strategies ensure the achievement of these goals.
      OBJECTIVES: This study compiles and synthesizes available scientific evidence
      from the last 14 years on the effectiveness of community intervention strategies
      for schizophrenia and related psychotic disorders. METHODOLOGY: An electronic
      search was carried out using PUBMED, LILACS, and Science Direct as databases.
      Criteria of inclusion: (i) randomized clinical trials, (ii) Community-based
      interventions, (iii) diagnosis of schizophrenia or related psychotic disorder
      (section F2 of ICD-10). EXCLUSION CRITERIA: (i) treatments exclusively
      pharmacological, (ii) interventions carried out in inpatient settings, (iii)
      bipolar affective disorder or substance-induced psychosis (greater than 50% of
      sample). RESULTS: Sixty-six articles were reviewed. Community strategies for
      integrated treatment from the first outbreak of schizophrenia significantly
      reduced negative and psychotic symptoms, days of hospitalization, and comorbidity
      with substance abuse and improved global functioning and adherence to treatment.
      In other stages, there were improved outcomes in negative and positive symptoms
      and general psychopathology. Psychoeducation for patients and families reduced
      the levels of self-stigma and domestic abuse, as well as improved knowledge of
      the disease and treatment adherence. Training focused on cognitive, social, and
      labor skills has been shown to improve yields in social functioning and
      employment status. CONCLUSION: Community-based intervention strategies are widely
      supported in the treatment of patients with schizophrenia.

PMID- 24130536
TI  - Theta brain rhythms index perceptual narrowing in infant speech perception.
AB  - The development of speech perception shows a dramatic transition between infancy
      and adulthood. Between 6 and 12 months, infants' initial ability to discriminate
      all phonetic units across the world's languages narrows-native discrimination
      increases while non-native discrimination shows a steep decline. We used
      magnetoencephalography (MEG) to examine whether brain oscillations in the theta
      band (4-8 Hz), reflecting increases in attention and cognitive effort, would
      provide a neural measure of the perceptual narrowing phenomenon in speech. Using
      an oddball paradigm, we varied speech stimuli in two dimensions, stimulus
      frequency (frequent vs. infrequent) and language (native vs. non-native speech
      syllables) and tested 6-month-old infants, 12-month-old infants, and adults. We
      hypothesized that 6-month-old infants would show increased relative theta power
      (RTP) for frequent syllables, regardless of their status as native or non-native
      syllables, reflecting young infants' attention and cognitive effort in response
      to highly frequent stimuli ("statistical learning"). In adults, we hypothesized
      increased RTP for non-native stimuli, regardless of their presentation frequency,
      reflecting increased cognitive effort for non-native phonetic categories. The 12
      month-old infants were expected to show a pattern in transition, but one more
      similar to adults than to 6-month-old infants. The MEG brain rhythm results
      supported these hypotheses. We suggest that perceptual narrowing in speech
      perception is governed by an implicit learning process. This learning process
      involves an implicit shift in attention from frequent events (infants) to learned
      categories (adults). Theta brain oscillatory activity may provide an index of
      perceptual narrowing beyond speech, and would offer a test of whether the early
      speech learning process is governed by domain-general or domain-specific
      processes. 

PMID- 24130537
TI  - Children's processing of emotion in ironic language.
AB  - IN THE PRESENT STUDY WE ADDRESSED TWO NOVEL QUESTIONS: (1) is children's irony
      appreciation and processing related to their empathy skills? and (2) is
      children's processing of a speaker's ironic meaning best explained by a modular
      or interactive theory? Participants were thirty-one 8- and 9-year-olds children.
      We used a variant of the visual world paradigm to assess children's processing of
      ironic and literal evaluative remarks; in this paradigm children's cognition is
      revealed through their actions and eye gaze. Results in this paradigm showed that
      children's irony appreciation and processing were correlated with their empathy
      development, suggesting that empathy or emotional perspective taking may be
      important for development of irony comprehension. Further, children's processing
      of irony was consistent with an interactive framework, in which children consider
      ironic meanings in the earliest moments, as speech unfolds. These results provide
      important new insights about development of this complex aspect of emotion
      recognition.

PMID- 24130538
TI  - Visual perspective and the characteristics of mind wandering.
AB  - When the mind wanders away from the here-and-now toward imaginary events, it
      typically does so from one of two visual vantage points-a first-person
      perspective (i.e., the world is seen as it is in everyday life) or a third-person
      perspective (i.e., the world is seen from the viewpoint of an outside observer).
      While extant evidence has detailed consequences that ensue from the utilization
      of these distinct points of view, less is known about their more basic
      properties. Here, we investigated the prevalence, demographics and qualities
      associated with the visual perspective that people spontaneously adopt when the
      mind wanders. The results from a cross-cultural survey (N = 400) revealed that
      almost half of the participants (46%) typically utilize a third-person
      perspective when mind wandering. Further, culture and gender were shown to impact
      the distribution of first- and third-person imagers. Specifically, a first-person
      perspective was more common among participants from Western nations and females,
      while participants from Eastern cultures resonated more strongly with a third
      person perspective. Moreover, these factors were also shown to impact qualities
      (e.g., temporal locus, vividness) of mental imagery. Taken together, the current
      findings elucidate the prevalence of first- and third-person visual perspectives
      and detail individual differences that influence the qualia of mind wandering. 

PMID- 24130535
TI  - High-frequency neural oscillations and visual processing deficits in
      schizophrenia.
AB  - Visual information is fundamental to how we understand our environment, make
      predictions, and interact with others. Recent research has underscored the
      importance of visuo-perceptual dysfunctions for cognitive deficits and
      pathophysiological processes in schizophrenia. In the current paper, we review
      evidence for the relevance of high frequency (beta/gamma) oscillations towards
      visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper,
      we examine the relationship between beta/gamma band oscillations and visual
      processing during normal brain functioning. We then summarize EEG/MEG-studies
      which demonstrate reduced amplitude and synchrony of high-frequency activity
      during visual stimulation in schizophrenia. In the final part of the paper, we
      identify neurobiological correlates as well as offer perspectives for future
      research to stimulate further inquiry into the role of high-frequency
      oscillations in visual processing impairments in the disorder. 

PMID- 24130540
TI  - Plasticity after perceptual narrowing for voice perception: reinstating the
      ability to discriminate monkeys by their voices at 12 months of age.
AB  - Differentiating individuals by their voice is an important social skill for
      infants to acquire. In a previous study, we demonstrated that the ability to
      discriminate individuals by voice follows a pattern of perceptual narrowing
      (Friendly et al., 2013). Specifically, we found that the ability to discriminate
      between two foreign-species (rhesus monkey) voices decreased significantly
      between 6 and 12 months of age. Also during this period, there was a trend for
      the ability to discriminate human voices to increase. Here we investigate the
      extent to which plasticity remains at 12 months, after perceptual narrowing has
      occurred. We found that 12-month-olds who received 2 weeks of monkey-voice
      training were significantly better at discriminating between rhesus monkey voices
      than untrained 12-month-olds. Furthermore, discrimination was reinstated to a
      level slightly better than that of untrained 6-month-olds, suggesting that voice
      processing abilities remain considerably plastic at the end of the first year. 

PMID- 24130539
TI  - Separating lexical-semantic access from other mnemonic processes in picture-name
      verification.
AB  - We present a novel paradigm to identify shared and unique brain regions
      underlying non-semantic, non-phonological, abstract, audio-visual (AV) memory vs.
      naming using a longitudinal functional magnetic resonance imaging experiment.
      Participants were trained to associate novel AV stimulus pairs containing hidden
      linguistic content. Half of the stimulus pairs were distorted images of animals
      and sine-wave speech versions of the animal's name. Images and sounds were
      distorted in such a way as to make their linguistic content easily recognizable
      only after being made aware of its existence. Memory for the pairings was tested
      by presenting an AV pair and asking participants to verify if the two stimuli
      formed a learned pairing. After memory testing, the hidden linguistic content was
      revealed and participants were tested again on their recollection of the pairings
      in this linguistically informed state. Once informed, the AV verification task
      could be performed by naming the picture. There was substantial overlap between
      the regions involved in recognition of non-linguistic sensory memory and naming,
      suggesting a strong relation between them. Contrasts between sessions identified
      left angular gyrus and middle temporal gyrus as key additional players in the
      naming network. Left inferior frontal regions participated in both naming and non
      linguistic AV memory suggesting the region is responsible for AV memory
      independent of phonological content contrary to previous proposals. Functional
      connectivity between angular gyrus and left inferior frontal gyrus and left
      middle temporal gyrus increased when performing the AV task as naming. The
      results are consistent with the hypothesis that, at the spatial resolution of
      fMRI, the regions that facilitate non-linguistic AV associations are a subset of
      those that facilitate naming though reorganized into distinct networks. 

PMID- 24130541
TI  - The next generation of obesity treatments: beyond suppressing appetite.

PMID- 24130542
TI  - Diminished acquired equivalence yet good discrimination performance in older
      participants.
AB  - We asked younger and older human participants to perform computer-based
      configural discriminations that were designed to detect acquired equivalence.
      Both groups solved the discriminations but only the younger participants
      demonstrated acquired equivalence. The discriminations involved learning the
      preferences ["like" (+) or "dislike" (-)] for sports [e.g., tennis (t) and hockey
      (h)] of four fictitious people [e.g., Alice (A), Beth (B), Charlotte (C), and
      Dorothy (D)]. In one experiment, the discrimination had the form: At+, Bt-, Ct+,
      Dt-, Ah-, Bh+, Ch-, Dh+. Notice that, e.g., Alice and Charlotte are "equivalent"
      in liking tennis but disliking hockey. Acquired equivalence was assessed in
      ancillary components of the discrimination (e.g., by looking at the subsequent
      rate of "whole" versus "partial" reversal learning). Acquired equivalence is
      anticipated by a network whose hidden units are shared when inputs (e.g., A and
      C) signal the same outcome (e.g., +) when accompanied by the same input (t). One
      interpretation of these results is that there are age-related differences in the
      mechanisms of configural acquired equivalence. 

PMID- 24130543
TI  - Option generation in decision-making research: why just talk?

PMID- 24130544
TI  - To disconfirm or not to disconfirm: a null prediction vs. no prediction.

PMID- 24130545
TI  - Much ado about p. What does a p-value mean when testing hypotheses with
      aggregated cross-cultural data in the field of evolution and human behavior?

PMID- 24130546
TI  - Detecting false intent using eye blink measures.
AB  - Eye blink measures have been shown to be diagnostic in detecting deception
      regarding past acts. Here we examined-across two experiments with increasing
      degrees of ecological validity-whether changes in eye blinking can be used to
      determine false intent regarding future actions. In both experiments, half of the
      participants engaged in a mock crime and then transported an explosive device
      with the intent of delivering it to a "contact" that would use it to cause a
      disturbance. Eye blinking was measured for all participants when presented with
      three types of questions: relevant to intent to transport an explosive device,
      relevant to intent to engage in an unrelated illegal act, and neutral questions.
      Experiment 1 involved standing participants watching a video interviewer with
      audio presented ambiently. Experiment 2 involved standing participants questioned
      by a live interviewer. Across both experiments, changes in blink count during and
      immediately following individual questions, total number of blinks, and maximum
      blink time length differentiated those with false intent from truthful intent
      participants. In response to questions relevant to intent to deliver an explosive
      device vs. questions relevant to intent to deliver illegal drugs, those with
      false intent showed a suppression of blinking during the questions when compared
      to the 10 s period after the end of the questions, a lower number of blinks, and
      shorter maximum blink duration. The results are discussed in relation to
      detecting deception about past activities as well as to the similarities and
      differences to detecting false intent as described by prospective memory and
      arousal. 

PMID- 24130547
TI  - Advanced analysis of free visual exploration patterns in schizophrenia.
AB  - BACKGROUND: Visual scanpath analyses provide important information about
      attention allocation and attention shifting during visual exploration of social
      situations. This study investigated whether patients with schizophrenia simply
      show restricted free visual exploration behavior reflected by reduced saccade
      frequency and increased fixation duration or whether patients use qualitatively
      different exploration strategies than healthy controls. METHODS: Scanpaths of 32
      patients with schizophrenia and age-matched 33 healthy controls were assessed
      while participants freely explored six photos of daily life situations (20
      s/photo) evaluated for cognitive complexity and emotional strain. Using fixation
      and saccade parameters, we compared temporal changes in exploration behavior,
      cluster analyses, attentional landscapes, and analyses of scanpath similarities
      between both groups. RESULTS: We found fewer fixation clusters, longer fixation
      durations within a cluster, fewer changes between clusters, and a greater
      increase of fixation duration over time in patients compared to controls.
      Scanpath patterns and attentional landscapes in patients also differed
      significantly from those of controls. Generally, cognitive complexity and
      emotional strain had significant effects on visual exploration behavior. This
      effect was similar in both groups as were physical properties of fixation
      locations. CONCLUSIONS: Longer attention allocation to a given feature in a scene
      and less attention shifts in patients suggest a more focal processing mode
      compared to a more ambient exploration strategy in controls. These visual
      exploration alterations were present in patients independently of cognitive
      complexity, emotional strain or physical properties of visual cues implying that
      they represent a rather general deficit. Despite this impairment, patients were
      able to adapt their scanning behavior to changes in cognitive complexity and
      emotional strain similar to controls.

PMID- 24130548
TI  - Metabolic crisis in severely head-injured patients: is ischemia just the tip of
      the iceberg?
AB  - Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults
      that negatively influence outcome. Clinicians commonly mix up these two types of
      insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker
      for both ischemia and metabolic crisis. However, LPR elevations during ischemia
      and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1
      LPR elevations with low oxygenation) is characterized by a drastic deprivation of
      energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal
      or high oxygenation) is associated with profound mitochondrial dysfunction but
      normal supply of energetic substrates. The discrimination between ischemia and
      metabolic crisis is crucial because conventional recommendations against ischemia
      may be detrimental for patients with metabolic crisis. Multimodal monitoring,
      including microdialysis and brain tissue oxygen monitoring, allows such
      discrimination, but these techniques are not easily accessible to all head
      injured patients. Thus, a new "gold standard" and adapted medical education are
      required to optimize the management of patients with metabolic crisis. 

PMID- 24130549
TI  - Long-Range Temporal Correlations, Multifractality, and the Causal Relation
      between Neural Inputs and Movements.
AB  - Understanding the causal relation between neural inputs and movements is very
      important for the success of brain-machine interfaces (BMIs). In this study, we
      analyze 104 neurons' firings using statistical, information theoretic, and
      fractal analysis. The latter include Fano factor analysis, multifractal adaptive
      fractal analysis (MF-AFA), and wavelet multifractal analysis. We find neuronal
      firings are highly non-stationary, and Fano factor analysis always indicates long
      range correlations in neuronal firings, irrespective of whether those firings are
      correlated with movement trajectory or not, and thus does not reveal any actual
      correlations between neural inputs and movements. On the other hand, MF-AFA and
      wavelet multifractal analysis clearly indicate that when neuronal firings are not
      well correlated with movement trajectory, they do not have or only have weak
      temporal correlations. When neuronal firings are well correlated with movements,
      they are characterized by very strong temporal correlations, up to a time scale
      comparable to the average time between two successive reaching tasks. This
      suggests that neurons well correlated with hand trajectory experienced a "re
      setting" effect at the start of each reaching task, in the sense that within the
      movement correlated neurons the spike trains' long-range dependences persisted
      about the length of time the monkey used to switch between task executions. A new
      task execution re-sets their activity, making them only weakly correlated with
      their prior activities on longer time scales. We further discuss the significance
      of the coalition of those important neurons in executing cortical control of
      prostheses. 

PMID- 24130550
TI  - Sleep microstructure and memory function.

PMID- 24130551
TI  - Blood-Based Indicators of Insulin Resistance and Metabolic Syndrome in Bottlenose
      Dolphins (Tursiops truncatus).
AB  - Similar to people with metabolic syndrome, bottlenose dolphins (Tursiops
      truncatus) can have a sustained postprandial hyperglycemia and hyperinsulinemia,
      dyslipidemia, and fatty liver disease. A panel of potential postprandial blood
      based indicators of insulin resistance and metabolic syndrome were compared among
      34 managed collection dolphins in San Diego Bay, CA, USA (Group A) and 16 wild,
      free-ranging dolphins in Sarasota Bay, FL, USA (Group B). Compared to Group B,
      Group A had higher insulin (2.1 +/- 2.5 and 13 +/- 13 MUIU/ml), glucose (87 +/-
      19 and 108 +/- 12 mg/dl), and triglycerides (75 +/- 28 and 128 +/- 45 mg/dl) as
      well as higher cholesterol (total, high-density lipoprotein cholesterol, and very
      low density lipoprotein cholesterol), iron, transferrin saturation, gamma
      glutamyl transpeptidase (GGT), alanine transaminase, and uric acid. Group A had
      higher percent unmodified adiponectin. While Group A dolphins were older, the
      same blood-based differences remained when controlling for age. There were no
      differences in body mass index (BMI) between the groups, and comparisons between
      Group B and Group A dolphins have consistently demonstrated lower stress hormones
      levels in Group A. Group A dolphins with high insulin (greater than 14 MUIU/ml)
      had higher glucose, iron, GGT, and BMI compared to Group A dolphins with lower
      insulin. These findings support that some dolphin groups may be more susceptible
      to insulin resistance compared to others, and primary risk factors are not likely
      age, BMI, or stress. Lower high-molecular weight adiponectin has been identified
      as an independent risk factor for type 2 diabetes in humans and may be a target
      for preventing insulin resistance in dolphins. Future investigations with these
      two dolphin populations, including dietary and feeding differences, may provide
      valuable insight for preventing and treating insulin resistance in humans. 

PMID- 24130552
TI  - Developmental profile and sexually dimorphic expression of kiss1 and kiss1r in
      the fetal mouse brain.
AB  - The hypothalamic-pituitary-gonadal axis (HPG) is a complex neuroendocrine circuit
      involving multiple levels of regulation. Kisspeptin neurons play essential roles
      in controlling the HPG axis from the perspectives of puberty onset, oscillations
      of gonadotropin releasing hormone (GnRH) neuron activity, and the pre-ovulatory
      LH surge. The current studies focus on the expression of kisspeptin during murine
      fetal development using in situ hybridization (ISH), quantitative reverse
      transcription real-time PCR (QPCR), and immunocytochemistry. Expression of mRNA
      coding for kisspeptin (KISS1) and its receptor KISS1R was observed at embryonic
      (E) day 13 by ISH. At E13 and other later ages examined, Kiss1 signal in
      individual cells within the arcuate nucleus (ARC) appeared stronger in females
      than males. ISH examination of agonadal steroidogenic factor-1 (Sf1) knockout
      mice revealed that E17 XY knockouts (KO) resembled wild-type (WT) XX females.
      These findings raise the possibility that gonadal hormones modulate the
      expression of Kiss1 in the ARC prior to birth. The sex and genotype differences
      were tested quantitatively by QPCR experiments in dissected hypothalami from mice
      at E17 and adulthood. Females had significantly more Kiss1 than males at both
      ages, even though the number of cells detected by ISH was similar. In addition,
      QPCR revealed a significant difference in the amount of Kiss1 mRNA in Sf1 mice
      with WT XY mice expressing less than XY KO and XX mice of both genotypes. The
      detection of immunoreactive KISS1 in perikarya of the ARC at E17 indicates that
      early mRNA is translated to peptide. The functional significance of this early
      expression of Kiss1 awaits elucidation. 

PMID- 24130553
TI  - Nitric Oxide-Induced Calcium Release: Activation of Type 1 Ryanodine Receptor, a
      Calcium Release Channel, through Non-Enzymatic Post-Translational Modification by
      Nitric Oxide.
AB  - Nitric oxide (NO) is a typical gaseous messenger involved in a wide range of
      biological processes. In our classical knowledge, effects of NO are largely
      achieved by activation of soluble guanylyl cyclase to form cyclic guanosine-3',
      5'-monophosphate. However, emerging evidences have suggested another signaling
      mechanism mediated by NO: "S-nitrosylation" of target proteins. S-nitrosylation
      is a covalent addition of an NO group to a cysteine thiol/sulfhydryl (RSH), and
      categorized into non-enzymatic post-translational modification (PTM) of proteins,
      contrasted to enzymatic PTM of proteins, such as phosphorylation mediated by
      various protein kinases. Very recently, we found novel intracellular calcium
      (Ca(2+)) mobilizing mechanism, NO-induced Ca(2+) release (NICR) in cerebellar
      Purkinje cells. NICR is mediated by type 1 ryanodine receptor (RyR1), a Ca(2+)
      release channel expressed in endoplasmic-reticular membrane. Furthermore, NICR is
      indicated to be dependent on S-nitrosylation of RyR1, and involved in synaptic
      plasticity in the cerebellum. In this review, molecular mechanisms and functional
      significance of NICR, as well as non-enzymatic PTM of proteins by gaseous
      signals, are described. 

PMID- 24130554
TI  - Detection and diagnosis of rice-infecting viruses.
AB  - Rice-infecting viruses have caused serious damage to rice production in Asian,
      American, and African countries, where about 30 rice viruses and diseases have
      been reported. To control these diseases, developing accurate, quick methods to
      detect and diagnose the viruses in the host plants and any insect vectors of the
      viruses is very important. Based on an antigen-antibody reaction, serological
      methods such as latex agglutination reaction and enzyme-linked immunosorbent
      assay have advanced to detect viral particles or major proteins derived from
      viruses. They aid in forecasting disease and surveying disease spread and are
      widely used for virus detection at plant protection stations and research
      laboratories. From the early 2000s, based on sequence information for the target
      virus, several other methods such as reverse transcription-polymerase chain
      reaction (RT-PCR) and reverse transcription-loop-mediated isothermal
      amplification have been developed that are sensitive, rapid, and able to
      differentiate closely related viruses. Recent techniques such as real-time RT-PCR
      can be used to quantify the pathogen in target samples and monitor population
      dynamics of a virus, and metagenomic analyses using next-generation sequencing
      and microarrays show potential for use in the diagnosis of rice diseases. 

PMID- 24130555
TI  - Susceptibility to tulathromycin in Mannheimia haemolytica isolated from feedlot
      cattle over a 3-year period.
AB  - Mannheimia haemolytica isolated from feedlot cattle were tested for tulathromycin
      resistance. Cattle were sampled over a 3-year period, starting 12 months after
      approval of tulathromycin for prevention and treatment of bovine respiratory
      disease. Nasopharyngeal samples from approximately 5,814 cattle were collected
      when cattle entered feedlots (N = 4) and again from the same cattle after >=60
      days on feed. The antimicrobial use history for each animal was recorded.
      Mannheimia haemolytica was isolated from 796 (13.7%) entry samples and 1,038
      (20.6%) >= 60 days samples. Of the cattle positive for M. haemolytica, 18.5, 2.9,
      and 2.4% were administered therapeutic concentrations of tulathromycin,
      tilmicosin, or tylosin tartrate, respectively. In addition, 13.2% were
      administered subtherapeutic concentrations of tylosin phosphate in feed. In years
      one and two, no tulathromycin-resistant M. haemolytica were detected, whereas
      five isolates (0.4%) were resistant in year three. These resistant isolates were
      collected from three cattle originating from a single pen, were all serotype 1,
      and were genetically related (>=89% similarity) according to pulsed-field gel
      electrophoreses patterns. The five tulathromycin-resistant isolates were multi
      drug resistant also exhibiting resistance to oxytetracycline, tilmicosin,
      ampicillin, or penicillin. The macrolide resistance genes erm(42), erm(A),
      erm(B), erm(F), erm(X) and msr(E)-mph(E), were not detected in the tulathromycin
      resistant M. haemolytica. This study showed that tulathromycin resistance in M.
      haemolytica from a general population of feedlot cattle in western Canada was low
      and did not change over a 3-year period after tulathromycin was approved for use
      in cattle. 

PMID- 24130556
TI  - Sensitive detection of measles virus infection in the blood and tissues of
      humanized mouse by one-step quantitative RT-PCR.
AB  - Live attenuated measles virus (MV) has long been recognized as a safe and
      effective vaccine, and it has served as the basis for development of various MV
      based vaccines. However, because MV is a human-tropic virus, the evaluation of MV
      based vaccines has been hampered by the lack of a small-animal model. The
      humanized mouse, a recently developed system in which an immunodeficient mouse is
      transplanted with human fetal tissues or hematopoietic stem cells, may represent
      a suitable model. Here, we developed a sensitive one-step quantitative reverse
      transcription (qRT)-PCR that simultaneously measures nucleocapsid (N) and human
      RNase P mRNA levels. The results can be used to monitor MV infection in a
      humanized mouse model. Using this method, we elucidated the replication kinetics
      of MV expressing enhanced green fluorescent protein both in vitro and in
      humanized mice in parallel with flow-cytometric analysis. Because our qRT-PCR
      system was sensitive enough to detect MV expression using RNA extracted from a
      small number of cells, it can be used to monitor MV infection in humanized mice
      by sequential blood sampling. 

PMID- 24130557
TI  - Can non-human primates serve as models for investigating dengue disease
      pathogenesis?
AB  - Dengue Virus (DV) infects between 50 and 100 million people globally, with public
      health costs totaling in the billions. It is the causative agent of dengue fever
      (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), vector-borne
      diseases that initially predominated in the tropics. Due to the expansion of its
      mosquito vector, Aedes spp., DV is increasingly becoming a global problem.
      Infected individuals may present with a wide spectrum of symptoms, spanning from
      a mild febrile to a life-threatening illness, which may include thrombocytopenia,
      leucopenia, hepatomegaly, hemorrhaging, plasma leakage and shock. Deciphering the
      underlining mechanisms responsible for these symptoms has been hindered by the
      limited availability of animal models that can induce classic human pathology.
      Currently, several permissive non-human primate (NHP) species and mouse breeds
      susceptible to adapted DV strains are available. Though virus replication occurs
      in these animals, none of them recapitulate the cardinal features of human
      symptomatology, with disease only occasionally observed in NHPs. Recently our
      group established a DV serotype 2 intravenous infection model with the Indian
      rhesus macaque, which reliably produced cutaneous hemorrhages after primary virus
      exposure. Further manipulation of experimental parameters (virus strain, immune
      cell expansion, depletion, etc.) can refine this model and expand its relevance
      to human DF. Future goals include applying this model to elucidate the role of
      pre-existing immunity upon secondary infection and immunopathogenesis. Of note,
      virus titers in primates in vivo and in vitro, even with our model, have been
      consistently 1000-fold lower than those found in humans. We submit that an
      improved model, capable of demonstrating severe pathogenesis may only be achieved
      with higher virus loads. Nonetheless, our DV coagulopathy disease model is
      valuable for the study of select pathomechanisms and testing DV drug and vaccine
      candidates. 

PMID- 24130558
TI  - Immunostimulation by synthetic lipopeptide-based vaccine candidates: structure
      activity relationships.
AB  - Peptide-based vaccines offer several advantages over conventional whole organism
      or protein approaches by offering improved purity and specificity in inducing
      immune response. However, peptides alone are generally non-immunogenic. Concerns
      remain about the toxicity of adjuvants which are critical for immunogenicity of
      synthetic peptides. The use of lipopeptides in peptide vaccines is currently
      under intensive investigation because potent immune responses can be generated
      without the use of adjuvant (thus are self-adjuvanting). Several lipopeptides
      derived from microbial origin, and their synthetic versions or simpler fatty acid
      moieties impart this self-adjuvanting activity by signaling via Toll-like
      receptor 2 (TLR2). Engagement of this innate immune receptor on antigen
      presenting cell leads to the initiation and development of potent immune
      responses. Therefore optimization of lipopeptides to enhance TLR2-mediated
      activation is a promising strategy for vaccine development. Considerable
      structure-activity relationships that determine TLR2 binding and consequent
      stimulation of innate immune responses have been investigated for a range of
      lipopeptides. In this mini review we address the development of lipopeptide
      vaccines, mechanism of TLR2 recognition, and immune activation. An overview is
      provided of the best studied lipopeptide vaccine systems. 

PMID- 24130561
TI  - Limited Effectiveness of Psoralen- and Ultraviolet-Inactivated Vaccinia Virus on
      SHIV Infection.

PMID- 24130560
TI  - The many faces of aire in central tolerance.
AB  - Although the role that Autoimmune Regulator (Aire) plays in the induction of
      central tolerance is well known, the precise cellular and molecular mechanisms
      are still unclear and debated. In the prevailing view, Aire serves mainly as a
      direct inducer of tissue-specific antigens. However, there is a growing amount of
      evidence suggesting that Aire modulates the differentiation program of medullary
      thymic epithelial cells, which may directly contribute to the negative selection
      of self-reactive thymocytes. In addition, Aire has been shown to regulate the
      expression of many intrathymic chemokines that are required for the proper
      localization of thymocytes and dendritic cells, and thus are potentially
      important for direct and indirect self-antigen presentation in the thymic
      medulla. Further, recent evidence suggests that the induction of certain antigen
      specific regulatory T-cells that translocate to tumors and peripheral tissues can
      be Aire dependent and may contribute to tissue-specific tolerance. This review
      summarizes the current understanding of the effects of Aire on these alternative
      mechanisms for the induction of Aire-induced central tolerance. 

PMID- 24130559
TI  - Messages from the Inside. The Dynamic Environment that Favors Intestinal
      Homeostasis.
AB  - An organism is defined as "an individual living thing capable of responding to
      stimuli, growing, reproducing, and maintaining homeostasis." Early during
      evolution multicellular organisms explored the advantages of a symbiotic life.
      Mammals harbor a complex aggregate of microorganisms (called microbiota) that
      includes bacteria, fungi, and archaea. Some of these bacteria have already
      defined beneficial roles for the human host that include the ability to break
      down nutrients that could not otherwise be digested, preventing the growth of
      harmful species, as well as the ability to produce vitamins or hormones. It is
      intuitive that along the evolutionary path several mechanisms favored bacteria
      that provided advantages to the host which, in return, avoided launching an
      aggressive immunological response against them. The intestinal immunological
      response does not ignore the lumenal content, on the contrary, immune
      surveillance is favored by continuous antigen sampling. Some intestinal
      epithelial cells (ECs) are crucial during the sampling process, others actively
      participate in the defense mechanism. In essence the epithelium acts as a traffic
      light, communicating to the inside world whether conditions are safe or
      dangerous, and thus influencing immunological response. In this review we will
      discuss the dynamic factors that act on the intestinal ECs and how they directly
      or indirectly influence immune cells during states of health and disease. 

PMID- 24130562
TI  - Recent Advances in Defining the Immunoproteome of Mycobacterium tuberculosis.
AB  - Immunity conferred by antigen-specific CD4+ T cells is critical for controlling
      infection with Mycobacterium tuberculosis (Mtb), the causative agent of
      tuberculosis. However, despite research that spans more than a century, many of
      the characteristics of protective immune responses to Mtb remain elusive.
      Defining the repertoire of antigenic targets is central to understanding the
      immune response against this pathogen. Although traditional methods of antigen
      discovery have identified many immunodominant antigens, they afford limited
      proteome coverage. Recent advances in proteomic techniques that are based on
      peptide library and protein microarray technology have enabled interrogation of
      the entire proteome of Mtb for antigens. Though these techniques have limitations
      and are still evolving, early studies using these techniques provide an unbiased
      view of the immune response to Mtb. Here we review proteome-wide approaches to
      antigen discovery and summarize what these have revealed so far on the
      composition of the Mtb immunoproteome. 

PMID- 24130564
TI  - Diversification of the phaseoloid legumes: effects of climate change, range
      expansion and habit shift.
AB  - Understanding which factors have driven the evolutionary success of a group is a
      fundamental question in biology. Angiosperms are the most successful group in
      plants and have radiated and adapted to various habitats. Among angiosperms,
      legumes are a good example for such successful radiation and adaptation. We here
      investigated how the interplay of past climate changes, geographical expansion
      and habit shifts has promoted diversification of the phaseoloid legumes, one of
      the largest clades in the Leguminosae. Using a comprehensive genus-level
      phylogeny from three plastid markers, we estimate divergence times, infer habit
      shifts, test the phylogenetic and temporal diversification heterogeneity, and
      reconstruct ancestral biogeographical ranges. We found that the phaseoloid
      lineages underwent twice dramatic accumulation. During the Late Oligocene, at
      least six woody clades rapidly diverged, perhaps in response to the Late
      Oligocene warming and aridity, and a result of rapidly exploiting new ecological
      opportunities in Asia, Africa and Australia. The most speciose lineage is
      herbaceous and began to rapidly diversify since the Early Miocene, which was
      likely ascribed to arid climates, along with the expansion of seasonally dry
      tropical forests in Africa, Asia, and America. The phaseoloid group provides an
      excellent case supporting the idea that the interplay of ecological opportunities
      and key innovations drives the evolutionary success. 

PMID- 24130563
TI  - Which role for nitric oxide in symbiotic N2-fixing nodules: toxic by-product or
      useful signaling/metabolic intermediate?
AB  - The interaction between legumes and rhizobia leads to the establishment of a
      symbiotic relationship characterized by the formation of new organs called
      nodules, in which bacteria have the ability to fix atmospheric nitrogen (N2) via
      the nitrogenase activity. Significant nitric oxide (NO) production was evidenced
      in the N2-fixing nodules suggesting that it may impact the symbiotic process.
      Indeed, NO was shown to be a potent inhibitor of nitrogenase activity and
      symbiotic N2 fixation. It has also been shown that NO production is increased in
      hypoxic nodules and this production was supposed to be linked - via a nitrate/NO
      respiration process - with improved capacity of the nodules to maintain their
      energy status under hypoxic conditions. Other data suggest that NO might be a
      developmental signal involved in the induction of nodule senescence. Hence, the
      questions were raised of the toxic effects versus signaling/metabolic functions
      of NO, and of the regulation of NO levels compatible with nitrogenase activity.
      The present review analyses the different roles of NO in functioning nodules, and
      discusses the role of plant and bacterial (flavo)hemoglobins in the control of NO
      level in nodules. 

PMID- 24130565
TI  - Plant roots and spectroscopic methods - analyzing species, biomass and vitality.
AB  - In order to understand plant functioning, plant community composition, and
      terrestrial biogeochemistry, it is decisive to study standing root biomass,
      (fine) root dynamics, and interactions belowground. While most plant taxa can be
      identified by visual criteria aboveground, roots show less distinctive features.
      Furthermore, root systems of neighboring plants are rarely spatially segregated;
      thus, most soil horizons and samples hold roots of more than one species
      necessitating root sorting according to taxa. In the last decades, various
      approaches, ranging from anatomical and morphological analyses to differences in
      chemical composition and DNA sequencing were applied to discern species' identity
      and biomass belowground. Among those methods, a variety of spectroscopic methods
      was used to detect differences in the chemical composition of roots. In this
      review, spectroscopic methods used to study root systems of herbaceous and woody
      species in excised samples or in situ will be discussed. In detail, techniques
      will be reviewed according to their usability to discern root taxa, to determine
      root vitality, and to quantify root biomass non-destructively or in soil cores
      holding mixtures of plant roots. In addition, spectroscopic methods which may be
      able to play an increasing role in future studies on root biomass and related
      traits are highlighted. 

PMID- 24130566
TI  - Endogenous auxin and jasmonic acid levels are differentially modulated by abiotic
      stresses in rice.
AB  - Abiotic stresses such as drought, salinity, and adverse temperatures are major
      limiting factors for plant growth and reproduction. Plant responses to these
      stresses are coordinated by arrays of regulatory networks including the induction
      of endogenous abscisic acid (ABA), a well documented phytohormone for stress
      responses. However, whether or how these abiotic stresses affect the endogenous
      biosynthesis or metabolism of other phytohormones remains largely unknown. Here,
      we report the changes of endogenous indole-3-acetic acid (IAA) and jasmonic acid
      (JA) levels and expression of genes related to the biosynthesis or signaling of
      these hormones in rice under various abiotic stress conditions. The IAA content
      was decreased after drought stress, but it was significantly increased under cold
      and heat stresses. And the auxin-regulated gravitropism of root tip was inhibited
      by cold stress. Many genes involved in the IAA biosynthesis and signaling were
      changed in transcript level under these stresses, and the changes were
      essentially in agreement with the change of endogenous IAA level. Interestingly,
      the endogenous JA content was increased markedly under drought and cold stresses,
      but it was reduced by heat stress. Accordingly, many genes involved in JA
      biosynthesis and signaling were induced by drought and cold treatment but these
      genes were significantly suppressed by heat stress. We concluded that endogenous
      levels of IAA and JA were differentially regulated by abiotic stresses in rice,
      implying diverse roles of these hormones in stress responses. 

PMID- 24130568
TI  - Dynamics of non-structural carbohydrates in three Mediterranean woody species
      following long-term experimental drought.
AB  - Stored non-structural carbohydrates (NSC) have been proposed as a key determinant
      of drought resistance in plants. However, the evidence for this role is
      controversial, as it comes mostly from observational, short-term studies. Here,
      we take advantage of a long-term experimental throughfall reduction to elucidate
      the response of NSC to increased drought 14 years after the beginning of the
      treatment in three Mediterranean resprouter trees (Quercus ilex L., Arbutus unedo
      L. and Phillyrea latifolia L.). In addition, we selected 20 Q. ilex individuals
      outside the experimental plots to directly assess the relationship between
      defoliation and NSC at the individual level. We measured the seasonal course of
      NSC concentrations in leaves, branches and lignotuber in late winter, late
      spring, summer, and autumn 2012. Total concentrations of NSC were highest in the
      lignotuber for all species. In the long-term drought experiment we found
      significant depletion in concentrations of total NSC in treatment plots only in
      the lignotuber of A. unedo. At the same time, A. unedo was the only species
      showing a significant reduction in BAI under the drought treatment during the 14
      years of the experiment. By contrast, Q. ilex just reduced stem growth only
      during the first 4 years of treatment and P. latifolia remained unaffected over
      the whole study period. However, we found a clear association between the
      concentrations of NSC and defoliation in Q. ilex individuals sampled outside the
      experimental plots, with lower total concentrations of NSC and lower proportion
      of starch in defoliated individuals. Taken together, our results suggest that
      stabilizing processes, probably at the stand level, may have been operating in
      the long-term to mitigate any impact of drought on NSC levels, and highlight the
      necessity to incorporate long-term experimental studies of plant responses to
      drought. 

PMID- 24130569
TI  - Antagonistic regulation of the meristemoid-to-guard mother-cell-transition.

PMID- 24130567
TI  - Nitric oxide and phytohormone interactions: current status and perspectives.
AB  - Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems,
      playing significant roles in a wide range of responses to environmental and
      endogenous cues. During the signaling events leading to these plant responses, NO
      frequently interacts with plant hormones and other endogenous molecules, at times
      originating remarkably complex signaling cascades. Accumulating evidence
      indicates that virtually all major classes of plant hormones may influence, at
      least to some degree, the endogenous levels of NO. In addition, studies conducted
      during the induction of diverse plant responses have demonstrated that NO may
      also affect biosynthesis, catabolism/conjugation, transport, perception, and/or
      transduction of different phytohormones, such as auxins, gibberellins,
      cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, and
      brassinosteroids. Although still not completely elucidated, the mechanisms
      underlying the interaction between NO and plant hormones have recently been
      investigated in a number of species and plant responses. This review specifically
      focuses on the current knowledge of the mechanisms implicated in NO-phytohormone
      interactions during the regulation of developmental and metabolic plant events.
      The modifications triggered by NO on the transcription of genes encoding
      biosynthetic/degradative enzymes as well as proteins involved in the transport
      and signal transduction of distinct plant hormones will be contextualized during
      the control of developmental, metabolic, and defense responses in plants.
      Moreover, the direct post-translational modification of phytohormone biosynthetic
      enzymes and receptors through S-nitrosylation will also be discussed as a key
      mechanism for regulating plant physiological responses. Finally, some future
      perspectives toward a more complete understanding of NO-phytohormone interactions
      will also be presented and discussed. 

PMID- 24130570
TI  - Paramo is the world's fastest evolving and coolest biodiversity hotspot.
AB  - Understanding the processes that cause speciation is a key aim of evolutionary
      biology. Lineages or biomes that exhibit recent and rapid diversification are
      ideal model systems for determining these processes. Species rich biomes reported
      to be of relatively recent origin, i.e., since the beginning of the Miocene,
      include Mediterranean ecosystems such as the California Floristic Province,
      oceanic islands such as the Hawaiian archipelago and the Neotropical high
      elevation ecosystem of the Paramos. Paramos constitute grasslands above the
      forest tree-line (at elevations of c. 2800-4700 m) with high species endemism.
      Organisms that occupy this ecosystem are a likely product of unique adaptations
      to an extreme environment that evolved during the last three to five million
      years when the Andes reached an altitude that was capable of sustaining this type
      of vegetation. We compared net diversification rates of lineages in fast evolving
      biomes using 73 dated molecular phylogenies. Based on our sample, we demonstrate
      that average net diversification rates of Paramo plant lineages are faster than
      those of other reportedly fast evolving hotspots and that the faster evolving
      lineages are more likely to be found in Paramos than the other hotspots. Paramos
      therefore represent the ideal model system for studying diversification
      processes. Most of the speciation events that we observed in the Paramos (144 out
      of 177) occurred during the Pleistocene possibly due to the effects of species
      range contraction and expansion that may have resulted from the well-documented
      climatic changes during that period. Understanding these effects will assist with
      efforts to determine how future climatic changes will impact plant populations. 

PMID- 24130571
TI  - The spliced leader trans-splicing mechanism in different organisms: molecular
      details and possible biological roles.
AB  - THE SPLICED LEADER (SL) IS A GENE THAT GENERATES A FUNCTIONAL NCRNA THAT IS
      COMPOSED OF TWO REGIONS: an intronic region of unknown function (SLi) and an
      exonic region (SLe), which is transferred to the 5' end of independent
      transcripts yielding mature mRNAs, in a process known as spliced leader trans
      splicing (SLTS). The best described function for SLTS is to solve polycistronic
      transcripts into monocistronic units, specifically in Trypanosomatids. In other
      metazoans, it is speculated that the SLe addition could lead to increased mRNA
      stability, differential recruitment of the translational machinery, modification
      of the 5' region or a combination of these effects. Although important aspects of
      this mechanism have been revealed, several features remain to be elucidated. We
      have analyzed 157 SLe sequences from 148 species from seven phyla and found a
      high degree of conservation among the sequences of species from the same phylum,
      although no considerable similarity seems to exist between sequences of species
      from different phyla. When analyzing case studies, we found evidence that a given
      SLe will always be related to a given set of transcripts in different species
      from the same phylum, and therefore, different SLe sequences from the same
      species would regulate different sets of transcripts. In addition, we have
      observed distinct transcript categories to be preferential targets for the SLe
      addition in different phyla. This work sheds light into crucial and controversial
      aspects of the SLTS mechanism. It represents a comprehensive study concerning
      various species and different characteristics of this important post
      transcriptional regulatory mechanism. 

PMID- 24130572
TI  - Annotation extension through protein family annotation coherence metrics.
AB  - Protein functional annotation consists in associating proteins with textual
      descriptors elucidating their biological roles. The bulk of annotation is done
      via automated procedures that ultimately rely on annotation transfer. Despite a
      large number of existing protein annotation procedures the ever growing protein
      space is never completely annotated. One of the facets of annotation
      incompleteness derives from annotation uncertainty. Often when protein function
      cannot be predicted with enough specificity it is instead conservatively
      annotated with more generic terms. In a scenario of protein families or
      functionally related (or even dissimilar) sets this leads to a more difficult
      task of using annotations to compare the extent of functional relatedness among
      all family or set members. However, we postulate that identifying sub-sets of
      functionally coherent proteins annotated at a very specific level, can help the
      annotation extension of other incompletely annotated proteins within the same
      family or functionally related set. As an example we analyse the status of
      annotation of a set of CAZy families belonging to the Polysaccharide Lyase class.
      We show that through the use of visualization methods and semantic similarity
      based metrics it is possible to identify families and respective annotation terms
      within them that are suitable for possible annotation extension. Based on our
      analysis we then propose a semi-automatic methodology leading to the extension of
      single annotation terms within these partially annotated protein sets or
      families. 

PMID- 24130573
TI  - A review of glass-ionomers: From conventional glass-ionomer to bioactive glass
      ionomer.
AB  - Materials used in the body, especially the materials used in various oral cavity
      regions should be stable and passive without any interactions with the body
      tissues or fluids. Dental amalgam, composite resins and dental cements are the
      materials of choice with such properties. The first attempts to produce active
      materials, which could interact with the human body tissues and fluids were
      prompted by the concept that fluoride-releasing materials exert useful effects in
      the body. The concept of using the "smart" materials in dentistry has attracted a
      lot of attention in recent years. Conventional glass-ionomer (GI) cements have a
      large number of applications in dentistry. They are biocompatible with the dental
      pulp to some extent. GI is predominantly used as cements in dentistry; however,
      they have some disadvantages, the most important of which is lack of adequate
      strength and toughness. In an attempt to improve the mechanical properties of the
      conventional GI, resin-modified glass-ionomers have been marketed, with
      hydrophilic monomers, such as hydroxyethyl methacrylated (HEMA). Some recent
      studies have evaluated GI with bioactive glass in its structure to validate the
      claims that such a combination will improve tooth bioactivity, regeneration
      capacity and restoration. There is ever-increasing interest in the application of
      bioactive materials in the dental field in an attempt to remineralize affected
      dentin. The aim of this review article is to evaluate these materials and their
      characteristics and applications. 

PMID- 24130574
TI  - Stem cells-the hidden treasure: A strategic review.
AB  - In today's scenario, medical and dental professionals face a mammoth task while
      treating perplexing medical situations like organ failure or tissue loss. Though,
      different strategies exist to replace them, but ideal one is the same natural
      tissue or organ. In this aspect, stem cells have emerged in a promising way to
      provide an ideal replacement. There are different types of stem cells starting
      from the embryonic stage referred to as human embryonic stem cells to adult stem
      cells. Though in dentistry stem cell research is lagging as compared to the
      medical field but still a lot progress has been achieved in recent years. The
      stem cells have been isolated from dental pulp, human exfoliated deciduous teeth,
      and apical papilla and so on. These stem cells have provided exciting results
      like dentin-pulp regeneration, periodontal regeneration but ambiguity still
      prevails. As a result, much has to be further researched before its clinical
      application becomes a reality. Hence, these stem cells opened a new avenue in the
      field of regenerative dentistry. 

PMID- 24130575
TI  - Detection of galectins during malignant transformation of oral cells.
AB  - Oral cancer is a common neoplasm world-wide. The incidence and mortality have
      increased over the past decades. It is characterized by poor prognosis and a low
      survival rate despite sophisticated surgical and radiotherapeutic modalities.
      Galectins are detected in a wide variety of tissues. The expression of galectins
      is modulated during the differentiation of individual cells and during the
      development of organisms and tissues, being altered in different physiological or
      pathological conditions including, carcinogenesis. In this review, we will
      discuss the role of galectins during the malignant transformation of oral cells,
      in order to understand their mechanisms of the action in a several cellular
      activities and test systems. Certainly, such information will contribute for
      understanding oral cancer pathogenesis. 

PMID- 24130576
TI  - Comparison of matrix metalloproteinase-3 and tissue inhibitor of matrix
      metalloproteinase-1 levels in gingival crevicular fluid in periodontal health,
      disease and after treatment: A clinico biochemical study.
AB  - BACKGROUND: Considering the role of matrix metalloproteinase-3 (MMP-3) and tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1) in the pathogenesis of
      periodontitis, the present study is to estimate the levels of MMP-3 and TIMP-1 in
      gingival crevicular fluid (GCF) in periodontal health, disease and to evaluate
      the effect of periodontal therapy on MMP-3 and TIMP-1 concentrations in GCF.
      MATERIALS AND METHODS: A periodontal examination and collection of GCF by extra
      crevicular method was performed in 30 subjects selected randomly and categorized
      into 3 groups. Group I consists of 10 subjects Group II consists of 20 patients
      and Group III consists of 20 patients of Group II. Non surgical periodontal
      therapy was performed, and GCF was collected after 8 weeks from the same site of
      20 chronic periodontitis patients who are considered as Group III. MMP- 3 and
      TIMP-1 levels were estimated in GCF-samples by using enzyme-linked immunosorbent
      assay. The findings were analyzed using the software and descriptive statistical
      methods such as Mann- Whitney U-test and Kruskal-Wallis test. P value < 0.001 was
      considered significant. RESULTS: MMP-3 and TIMP-1 was detected in all samples.
      Highest mean MMP-3 concentrations in GCF were obtained for Group II (7.490 ng/ml)
      while the lowest concentrations were seen in Group I (0.344 ng/ml) and Group III
      (2.129 ng/ml). This suggests that MMP-3 levels in GCF increases proportionally
      with the progression of periodontal disease and decreases after treatment. Lowest
      mean TIMP-1 concentrations in GCF were obtained for Group-II (1.592 ng/ml), while
      the highest concentrations were seen in Group-I (8.78 ng/ml) and Group-III (6.40
      ng/ml). This suggests that TIMP-1 levels in GCF decreases proportionally with
      progression of periodontal disease and increases after treatment. CONCLUSION:
      There is a substantial increase in the concentrations of MMP-3 and decrease in
      TIMP-1 as periodontal disease progress. Since MMP-3 and TIMP-1 levels in GCF are
      positively correlated with gingival index, probing pocket depth, and clinical
      attachment loss, MMP-3, and TIMP-1 may be considered as a Novel Biomarkers in
      periodontal disease. However, controlled, longitudinal studies are needed to
      confirm this possibility.

PMID- 24130577
TI  - Frequency, biofilm formation and acid susceptibility of streptococcus mutans and
      streptococcus sobrinus in saliva of preschool children with different levels of
      caries activity.
AB  - BACKGROUND: One of the causative factors in development of dental caries is
      microorganisms. Two species of Mutans streptococci including Streptococcus mutans
      and Streptococcus sobrinus are associated with dental caries in human beings. The
      aim of this study was to investigate the frequency of S. mutans and S. sobrinus
      in saliva of children with different caries activity and ability to form biofilm
      and acid susceptibility of these microorganisms. MATERIALS AND METHODS: This
      analytical case-control study was performed on 83 preschool children, 4-6 years
      old. Children were divided into two groups including 41 caries-active and 42
      caries-free children. Non-stimulated saliva samples were collected and culture
      and polymerase chain reaction techniques were used. Statistical analysis was
      performed using t-test, Chi-square, ANOVA, and Kappa tests. RESULTS: S. mutans
      and S. sobrinus were found in 65% and 21.6% of the samples respectively. S.
      mutans was isolated from 75.6% of caries-active and 54.8% of caries-free
      children. Figures for S. sobrinus were 29.2% and 14.3% respectively. Acid
      susceptibility of microorganisms isolated from saliva was 87.43 in caries-active
      children and 94.30 for caries-free children. Biofilm formation of microorganisms
      in caries-active and caries-free children was 0.77 and 0.73, respectively.
      CONCLUSION: Frequency of S. mutans in caries-active children was significantly
      higher than caries-free children, but the difference in frequency of S. sobrinus
      was not significant. Acid susceptibility of microorganisms in caries-active
      children was significantly lower, but the ability to form biofilm was not
      significantly different in two groups.

PMID- 24130578
TI  - Status of occupational hazards and their prevention among dental professionals in
      Chandigarh, India: A comprehensive questionnaire survey.
AB  - BACKGROUND: To assess the status of occupational hazards and their prevention
      among the practicing dentists in Chandigarh city, India. MATERIALS AND METHODS: A
      closed-ended questionnaire was prepared to record demographic status, types of
      occupational hazards encountered, and status of measures used for their
      prevention. A total 113 out of 130 dentists completed the questionnaire and the
      response rate was 86.9%. Frequency tables were prepared and coefficient of
      correlation was computed to check correlation between different variables.
      Statistical significance was set at P < 0.05. RESULTS: The most common
      occupational hazard reported was injury from "sharps" (77%), out of which needle
      prick injury was the most frequent. Of the other occupational problems job
      related stress (43.3%), musculoskeletal problems (39.8%), and allergies (23.8%)
      from things used in dental clinics were most common. A reasonably high percentage
      of dentists were immunized against hepatitis-B virus (88.4%) and were following
      proper infection control measures and hospital waste disposal methods. Very few
      dentists were following the correct method of disposal of excess amalgam (11%)
      and measurement of radiation exposure (27.5%) within their clinic. Most of them
      (90.2%) were satisfied with their current working hours and job. CONCLUSION:
      Prevalence of occupational hazards among the studied group was high and certain
      preventive measures were not being followed properly. Therefore, there is a need
      to improve the knowledge of dentists regarding these hazards and their
      prevention.

PMID- 24130579
TI  - Fluoride release and bioactivity evaluation of glass ionomer: Forsterite
      nanocomposite.
AB  - BACKGROUND: The most important limitation of glass ionomer cements (GICs) is the
      weak mechanical properties. Our previous research showed that higher mechanical
      properties could be achieved by addition of forsterite (Mg2SiO4) nanoparticles to
      ceramic part of GIC. The objective of the present study was to fabricate a glass
      ionomer- Mg2SiO4 nanocomposite and to evaluate the effect of addition of Mg2SiO4
      nanoparticles on bioactivity and fluoride release behavior of prepared
      nanocomposite. MATERIALS AND METHODS: Forsterite nanoparticles were made by sol
      gel process. X-ray diffraction (XRD) technique was used in order to phase
      structure characterization and determination of grain size of Mg2SiO4 nanopowder.
      Nanocomposite was fabricated via adding 3wt.% of Mg2SiO4 nanoparticles to ceramic
      part of commercial GIC (Fuji II GC). Fluoride ion release and bioactivity of
      nanocomposite were measured using the artificial saliva and simulated body fluid
      (SBF), respectively. Bioactivity of specimens was investigated by Fourier
      transitioned-infrared spectroscopy (FTIR), scanning electronmicroscopy (SEM),
      Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and
      registration of the changes in pH of soaking solution at the soaking period.
      Statistical analysis was carried out by one Way analysis of variance and
      differences were considered significant if P < 0.05. RESULTS: The results of XRD
      analysis confirmed that nanocrystalline and pure Mg2SiO4 powder was obtained.
      Fluoride ion release evaluation showed that the values of released fluoride ions
      from nanocomposite are somewhat less than Fuji II GC. SEM images, pH changes of
      the SBF and results of the ICP-OES and FTIR tests confirmed the bioactivity of
      the nanocomposite. Statistical analysis showed that the differences between the
      results of all groups were significant (P < 0.05). CONCLUSION: Glass ionomer-
      Mg2SiO4 nanocomposite could be a good candidate for dentistry and orthopedic
      applications, through of desirable fluoride ion release and bioactivity.

PMID- 24130580
TI  - Correlation between bone mineral density of jaws and skeletal sites in an Iranian
      population using dual X-ray energy absorptiometry.
AB  - BACKGROUND: The aim of the present study was to evaluate the relationship between
      the bone density of various regions of jaws and skeletal bones. MATERIALS AND
      METHODS: A total of 110 patients with a mean age of 55.01 +/- 10.77 years were
      selected for the purpose of the present descriptive study. Dual X-ray Energy
      Absorptiometry (DXA) was carried out to determine bone mineral density (BMD) of
      the femur and lumbar vertebrae. Then all the subjects underwent DXA of the jaw
      bones and BMD values were determined at four jaw regions. Data were analyzed by
      SPSS 16 statistical software, and the correlation between the various BMD values
      was determined by Pearson's correlation coefficient. RESULTS: The results showed
      that 42.7% of females had normal BMD values in the femur, and in vertebrae, 20%
      were osteopenic and 37.3% suffered from osteoporosis, with statistically
      significant differences in the BMD values of the jaws between the three above
      mentioned groups (P < 0.001). There was an increasing tendency toward osteopenia
      and osteoporosis with age. There was a positive correlation between BMD values of
      the femur and lumbar vertebrae and those of all the jaw regions under study (P <
      0.005). There was a negative correlation (P < 0.01) between age and the BMD
      values of the femur, lumbar vertebrae and anterior maxilla. CONCLUSION: The bone
      density of the maxilla and mandible and presence of osteoporosis or osteopenia in
      these bones might reflect the same problem in skeletal bones.

PMID- 24130581
TI  - Assessment of psychological dependence among tobacco users: A survey held among
      the rural population of India to call for attention of tobacco cessation centers.
AB  - BACKGROUND: In India most of the tobacco cessation centers are concentrating only
      on urban population, whereas, literature reveals that it is rural population,
      which shows high frequency of consumption of tobacco. It is well known that high
      frequency of tobacco consumption is associated with psychological dependence.
      This study aimed at identifying, which form of tobacco consumption (smoking or
      smokeless) is associated with psychological dependence and is associated with
      which particular age group in rural population. MATERIALS AND METHODS: It was a
      questionnaire based survey where 200 subjects were enrolled. Revised version of
      standard Fagerstrom Test for Nicotine dependence (FTND) was given to each subject
      to answer. The collected data was statistically analyzed by using Karl Pearson
      Correlation (r) test and Student's t-test. RESULTS: Study showed that subjects
      above 40 years of age are psychologically highly dependent on tobacco smoking as
      compared to tobacco chewing. Tobacco chewing is more prevalent among the younger
      population (20-30 years of age) and type of habit does not have any influence
      over psychological dependence below 40 years of age. A positive correlation was
      observed between duration of habit and psychological dependence in all age groups
      irrespective of type of the habit of tobacco consumption. CONCLUSION: This study
      attempts at creating a new avenue for the tobacco cessation centers where they
      can target their efforts towards rural population particularly people above 40
      years of age with a tobacco smoking habit so that they can actually reduce the
      burden of a number of people at risk for developing tobacco associated oral
      cancer.

PMID- 24130582
TI  - Evaluation of cortisol levels in gingival crevicular fluid and saliva in anxious
      and non-anxious patients with chronic periodontitis.
AB  - BACKGROUND: To evaluate gingival crevicular fluid (GCF) and salivary cortisol
      levels in anxious and non-anxious patients with chronic periodontitis. MATERIALS
      AND METHODS: A total of 45 patients with a mean age 43.4 +/- 6.12 years were
      assigned to three groups: Healthy control group (Group 1), group with chronic
      periodontitis but no anxiety (Group 2) and group with chronic periodontitis and
      with anxiety (Group 3). State - Trait anxiety inventory and Hamilton Anxiety
      rating scale were used to assess the anxiety levels of all the subjects. Clinical
      measures such as plaque index (PI), gingival index (GI), probing pocket depth
      (PPD) and clinical attachment level (CAL) were recorded. GCF and unstimulated
      whole saliva samples were collected, and cortisol levels were determined using
      ELISA kit. RESULTS: PI, GI, PPD, and CAL were higher in Group 3. Hormone level
      was significantly higher in Group 3. A positive correlation was found among
      salivary and GCF cortisol and CAL in Group 3. CONCLUSION: Based on the obtained
      results individuals with high-levels of anxiety seem to be more prone to have
      periodontal disease. Salivary and GCF cortisol levels can be used as biomarker
      for evaluating part of the etiopathogenesis of chronic periodontitis.

PMID- 24130583
TI  - Knowledge, attitudes, and performance of dental students in relation to
      sterilization/disinfection methods of extracted human teeth.
AB  - BACKGROUND: Dental students use extracted human teeth to learn practical and
      technical skills before they enter the clinical environment. In the present
      research, knowledge, performance, and attitudes toward sterilization/disinfection
      methods of extracted human teeth were evaluated in a selected group of Iranian
      dental students. MATERIALS AND METHODS: In this descriptive cross-sectional study
      the subjects consisted of fourth-, fifth- and sixth-year dental students. Data
      were collected by questionnaires and analyzed by Fisher's exact test and Chi
      squared test using SPSS 11.5. RESULTS: In this study, 100 dental students
      participated. The average knowledge score was 15.9 +/- 4.8. Based on the opinion
      of 81 students sodium hypochlorite was selected as suitable material for
      sterilization and 78 students believed that oven sterilization is a good way for
      the purpose. The average performance score was 4.1 +/- 0.8, with 3.9 +/- 1.7 and
      4.3 +/- 1.1 for males and females, respectively, with no significant differences
      between the two sexes. The maximum and minimum attitude scores were 60 and 25,
      with an average score of 53.1 +/- 5.2. CONCLUSION: The results of this study
      indicated that knowledge, performance and attitude of dental students in relation
      to sterilization/disinfection methods of extracted human teeth were good.
      However, weaknesses were observed in relation to teaching and materials suitable
      for sterilization.

PMID- 24130584
TI  - Effect of home-used water purifier on fluoride concentration of drinking water in
      southern Iran.
AB  - BACKGROUND: Fluoride in drinking water plays a key role in dental health. Due to
      the increasing use of water-purifier, the effect of these devices on fluoride
      concentration of drinking water was evaluated. MATERIALS AND METHODS: Drinking
      water samples were collected before and after passing through a home water
      purifier, from four different water sources. The fluoride, calcium and magnesium
      concentration of the samples were measured using the quantitative
      spectrophotometery technique. Data were analyzed by the Wilcoxon test. P value <
      0.1 was considered as significant. RESULTS: The result showed that the
      concentration of fluoride was 0.05-0.61 ppm before purification and was removed
      completely afterward. Furthermore, other ions reduced significantly after
      treatment by the water purifier. CONCLUSION: This study revealed that this device
      decreases the fluoride content of water, an issue which should be considered in
      low and high-fluoridated water sources.

PMID- 24130585
TI  - Effect of an herb root extract, herbal dentifrice and synthetic dentifrice on
      human salivary amylase.
AB  - BACKGROUND: Salivary amylase is an enzyme, which plays a vital role in formation
      of dental plaque. It has the ability to bind on the bacterial surfaces and to
      hydrolyze starch, giving rise to products that are transformed into acids leading
      to dental caries. Suppression of salivary amylase activity can lead to decrease
      in risk of dental caries and plaque associated periodontal diseases. The aim of
      this study was to evaluate the effect of an herb, Spilanthes calva (in form of a
      test dentifrice) on human salivary amylase activity and to compare it with other
      dentifrices. MATERIALS AND METHODS: A total of 80 subjects of age 18-35 years
      were randomly selected and divided equally into 4 groups. Group 1 subjects were
      assigned to use Test Dentifrice (with S. calva root extract), while Group 2,
      Group 3, and Group 4 subjects were assigned to use Herbal Dentifrice
      (Arodent(TM)), Synthetic Dentifrice (Colgate((r))), and Control Dentifrice
      respectively. Salivary amylase activity was determined by Bernfeld method in each
      group, before and after using the given dentifrices. RESULTS: Maximum inhibition
      of salivary amylase activity was found in the group using test dentifrice as
      compared to others. CONCLUSION: The present study indicates that, the root
      extract of S. calva possess significant inhibitory activity for salivary amylase.
      Use of S. calva root extract will provide a wider protection against different
      pathogenic oral microflora. Use of this extract singly or in combination is
      strongly recommended in the dentifrice formulations.

PMID- 24130586
TI  - The effect of zinc oxide nanoparticles deposition for friction reduction on
      orthodontic wires.
AB  - BACKGROUND: In the sliding technique, the reduced frictional forces are
      associated with rapid tooth movements and better control of the anchorage.
      Recently, wire coating with different nanoparticles has been proposed to decrease
      frictional forces. This in vitro study was carried out to coat stainless steel
      (SS) wires with zinc oxide (ZnO) nanoparticles in order to determine the effect
      of this coating on friction between wires and orthodontic brackets. MATERIALS AND
      METHODS: Eighty 0.016 inch and 0.019 inch * 0.025 inch SS wires with and without
      ZnO nanoparticles were used in 80 orthodontic brackets (0.018 and 0.022 systems).
      The coated wires were analyzed by SEM and X-Ray diffraction (XRD) observations.
      Kinetic friction between the wires and orthodontic brackets were calculated using
      a universal testing machine. Frictional forces were statistically analyzed using
      three-way ANOVA, one-way ANOVA, Student's t-test and Tukey multiple comparison
      tests. RESULTS: Coating with ZnO nanoparticles significantly influenced
      frictional force values (P < 0.0001). In 0.019 inch * 0.025 inch wires, the
      frictional forces were 1.6912 +/- 0.18868 and 3.4485 +/- 0.32389 N in the coated
      and uncoated wires respectively, (51% reductions). In the 0.016 inch wires, the
      friction values were estimated to be 1.5668 +/- 0.10703 and 2.56 +/- 0.34008 N in
      the coated and uncoated conditions, respectively, (39% reductions). CONCLUSION:
      Due to the positive effects of ZnO nanoparticle coating on decreasing frictional
      forces, these nanoparticles might offer a novel opportunity to significantly
      reduce friction during tooth movement.

PMID- 24130587
TI  - Comparison of the clinical outcomes of connective tissue and acellular dermal
      matrix in combination with double papillary flap for root coverage: A 6-month
      trial.
AB  - BACKGROUND: Different techniques have been proposed for the treatment of gingival
      recession. The majority of current procedures use autogenous soft-tissue grafts,
      which are associated with morbidity at the donor sites. Acellular dermal matrix
      (ADM) Alloderm is an alternative donor material presented to reduce related
      morbidity and provide more volume of the donor tissue. This study aimed to
      evaluate the effectiveness of an ADM allograft for root coverage and to compare
      it with a connective tissue graft (CTG), when used with a double papillary flap.
      MATERIALS AND METHODS: Sixteen patients with bilateral class I or II gingival
      recessions were selected. A total of 32 recessions were treated and randomly
      assigned into the test and contralateral recessions into the control group. In
      the control group, the exposed root surfaces were treated by the placement of a
      CTG in combination with a double papillary flap; and in the test group, an ADM
      allograft was used as a substitute for palatal donor tissue. Probing depth,
      clinical attachment level, width of keratinized tissue (KT), recession height and
      width were measured before, and after 2 weeks and 6 months of surgery. RESULTS:
      There were no statistically significant differences between the test and control
      groups in terms of recession reduction, clinical attachment gain, and reduction
      in probing depth. The control group had a statistically significant increased
      area of KT after 6 months compared to the test group. CONCLUSION: ADM allograft
      can be considered as a substitute for palatal donor tissue in root coverage
      procedure.

PMID- 24130588
TI  - A comparative study of histological grade and expression of Ki67 protein in oral
      squamous cell carcinoma in young and old patients.
AB  - BACKGROUND: Oral squamous cell carcinoma (SCC) is the most common cancer of oral
      region. The characteristic feature of SCC is invasion of dysplastic epithelium
      into the connective tissue. Oral SCC is more common in old patients. It is
      believed that etiology and pathogenesis of SCC in young patients differ from old
      patients and it is related to different molecular mechanism. In this study,
      histopathologic differentiation and proliferation activity (by Ki67) in oral SCC
      lesions of young patient (<40 years) and old patients (>50 years) have been
      compared. MATERIALS AND METHODS: In a cohort study, Formalin Fixed and paraffin
      embedded tissue sections of 20 oral SCC of young patients and 20 oral SCC of old
      patients were stained by H and E and immunohistochemically by biotin-streptavidin
      method. They were observed by two pathologists. Histological grade and Ki67
      labeling index (LI) were determined. Data were analyzed by t-test and Mann
      Whitney. RESULTS: In cases of oral SCC in young patients, 80% were grade I and
      20% were grade II and Ki67 LI was 21/5% in this age group. In cases of oral SCC
      in old patients, 75% were grade I and 25% were grade II and Ki67 LI was 21/6% in
      this age group. CONCLUSION: Histological and immunohistochemical evidence of this
      study show that oral SCC of young patients and oral SCC lesions of old patients
      didn't show any differences in histopathological differention and proliferative
      activity.

PMID- 24130589
TI  - Histological assessment of intra-articular versus intra-peritoneal betamethasone
      L.A on tempromandibular joint arthritis in rat.
AB  - BACKGROUND: Pain and dysfunction of the tempromandibular joint (TMJ) are major
      clinical problems, especially, in arthritis. The aim of this study was to compare
      the effect of intra-articular (IA) versus intra-peritoneal (IP) injection of
      betamethasone long acting on TMJ arthritis in rat. MATERIALS AND METHODS: In this
      experimental study, an inflammation in the left TMJ of 29 rats was induced by
      injection of complete Freund's adjuvant. After 1 week, rats were divided into 5
      groups: Group A: Rats of this group were not treated (n = 5); groups B, C: Rats
      were injected with a single dose of 1/2 mg/kg betamethasone L.A IA (n = 6);
      groups D, E: Rats received a single dose of 1/2 mg/kg betamethasone L.A IP (n =
      6). Rats in groups B and D after 1 week, and in groups C, E and A, at 4 weeks
      after drug injection were sacrificed. Severity of inflammation was scored from 1
      to 11 according to synovial hyperplasia, vascularity, fibrin deposits, and
      synovial adhesion. Results were analyzed by using Kruskal-Wallis and Mann-Whitney
      (P < 0/05 was considered significant). RESULTS: Significant differences were
      existed between groups B, D (P = 0/004) and groups C, E (P = 0/002). The least
      severity of Inflammation and also evidence of resorbtion in condylar head was
      seen in group C. CONCLUSION: The best therapeutic response was seen with IA
      injection of betamethasone L.A in comparison with IP injection.

PMID- 24130590
TI  - How will mandibular third molar surgery affect mandibular second molar
      periodontal parameters?
AB  - BACKGROUND: Several conflicting findings have been published in the previous
      literature regarding the effects of impacted third molar surgery on the
      periodontal parameters of the adjacent second molar; some authors have shown
      improvement of periodontal health distal to the adjacent second molar, whilst
      others have demonstrated loss of attachment level (AL) and reduction of alveolar
      bone height. The purpose of this study was to evaluate the changes in periodontal
      health parameters distal to the adjacent second molar following extraction of an
      impacted third molar. MATERIALS AND METHODS: Out of 50 patients participated in
      the study, 42 patients completed the study. The mean age of the sample was 20.9
      (range, 18-25) years. All teeth were mesioangular impacted mandibular third
      molars categorized at C1 class based on the Pell and Gregory classification. All
      surgeries were performed by one surgeon and the same surgeon recorded the pre
      operative and post-operative measurements of probing depth (PD) and AL on the
      distobuccal aspect of the second molars. Data analysis were carried out with the
      SPSS software (version 19), using the paired-samples t-test and one sample t
      test. RESULTS: Surgical extraction of impacted mandibular third molar resulted in
      a significant increase of PD on the distobuccal aspect of the second molars,
      whereas AL was decreased significantly after surgery (P < 0.05). CONCLUSION:
      Unlike plenty of researches that have shown improvement of periodontal parameters
      of the second molar after extraction of impacted third molar, our study showed a
      significant increase in PD at the distal aspect of the second molar. Further
      follow-up on clinical and radiological parameters are required for more profound
      understanding of the long-term effects of third molar extraction on the
      periodontal parameters of the adjacent second molar.

PMID- 24130591
TI  - Management of oral submucous fibrosis by two different drug regimens: A
      comparative study.
AB  - BACKGROUND: Oral Submucous Fibrosis (OSF) is a precancerous condition of the oral
      mucosa. Existing treatments give only temporary symptomatic relief. Colchicine is
      an ancient drug with anti-fibrotic and anti-inflammatory properties. We planned
      to study the effects of colchicine in the management of oral submucous fibrosis.
      MATERIALS AND METHODS: Fifty OSF patients were divided randomly into two groups
      and treated for 12 weeks. Group 1-Patients were administered tablet colchicine
      orally, 0.5 mg twice daily and 0.5 ml intralesional injection Hyaluronidase 1,500
      IU into each buccal mucosa once a week. Group 2-Patients were administered 0.5 ml
      intralesional injection Hyaluronidase 1,500 IU and 0.5 ml intralesional injection
      Hydrocortisone acetate 25 mg/ml in each buccal mucosa once a week alternatively.
      Student's t test and analysis of variance (ANOVA) were used to compare pre and
      post treatment results. P<0.05 was considered as significant. RESULTS: Thirty
      three percent in group 1 got relief from burning sensation in the second week.
      Inter group comparisons of increase in mouth opening and reduction in
      histological parameters indicated that group 1 patients responded better than
      group 2. CONCLUSION: These encouraging results should prompt further clinical
      trials with colchicine alone on a larger sample size to broaden the therapeutic
      usefulness of the drug in the management of OSF.

PMID- 24130592
TI  - Periodontal status and its risk factors among young adults of the Sebha city
      (Libya).
AB  - BACKGROUND: The occurrence of periodontal diseases in humans has been a global
      problem. Certain risk factors affect the initiation, progression, and severity of
      periodontitis. The present study has been designed to assess the periodontal
      status in relation to risk factors such as age, gender, oral hygiene practices,
      and smoking among the young adults of the Sebha city in Libya. MATERIALS AND
      METHODS: A cross-sectional study was carried out among 1,255 subjects aged
      between 18 years and 34 years. 1,006 (80.15%) subjects were females and 249
      (19.84%) subjects were males. Data was generated by conducting interview and
      clinical examination. The periodontal status was assessed by using Community
      Periodontal Index of Community Periodontal Index of Treatment Needs. The Chi
      square test and analysis of variance were used for statistical analysis at 5%
      level of significance. RESULTS: A total of 89.08% reported the use of toothbrush
      and toothpaste for cleaning and 10.91% used other aids, such as finger and Siwak.
      Of the 1,255 subjects, 3.98% were current smokers (all males). Only 4.7% had
      healthy periodontium (CPI code 1), while majority of 44.30% were detected with
      calculus (CPI code 2). Nearly 40.63% had shallow pockets (CPI code 3), 6.29% had
      bleeding (CPI code 1), and 4.06% had deep pockets (CPI code 4). The overall mean
      CPI score was 2.33 (0.84). Age and gender showed a statistically significant
      difference with the CPI codes. CONCLUSION: The result of this study provides
      baseline information for planning a preventive program. With preventive
      procedures being implemented at this young age, there is a possibility that the
      prevalence of periodontal disease will be lesser during adulthood.

PMID- 24130593
TI  - Wettability changes in polyether impression materials subjected to immersion
      disinfection.
AB  - BACKGROUND: Disinfection of impression materials prevents cross-contamination;
      however, the disinfectants may alter the wettability property. The purpose of
      this investigation was to evaluate the wettability changes of polyether
      impression material after immersing in four different chemical disinfectant
      solutions for a period of 10 min and 30 min, respectively. MATERIALS AND METHODS:
      A total of 45 samples of polyether dental impression material (Impregum soft,
      3MESPE, St. Paul, MN, USA) were randomly divided into nine groups with five
      specimens each. Each specimen was disc shaped, flat of 32 mm diameter and 3 mm
      thickness. The samples were immersed in four disinfectant solutions: 2%
      Glutaraldehyde, 5% sodium hypochlorite, 0.05% iodophor, and 5.25% phenol for 10
      min and 30 min, respectively. The control was without disinfection. Wettability
      of the samples was assessed by measuring the contact angle by using the
      Telescopic Goniometer. Data were subjected to analysis of variance (Fisher's
      test) and Tukey's post hoc test for multiple comparisons at 5% level of
      significance. RESULTS: The contact angle of 20.21 degrees  +/- 0.22 degrees  were
      recorded in the control samples. After 10 min, the samples that were immersed in
      5% sodium hypochlorite and 5.25% phenol showed significant statistical increase
      in the contact angle as compared to the control (P < 0.001). After 30 min of
      disinfection, only the samples immersed in 0.05% iodophor showed there were no
      significant changes in the contact angle, whereas the other disinfectants
      significantly increased the contact angle and decreased the wettability of the
      polyether material. CONCLUSION: Within the limitations of the study, 2%
      glutaraldehyde proved safe for 10 min of immersion disinfection while 0.05%
      iodophor holds promise as an effective disinfectant without affecting the
      wettability of the material.

PMID- 24130594
TI  - Effect of different post-space pretreatments on fiber post bonding to root
      dentine.
AB  - BACKGROUND: Before the resin bond endodontic post-cementation, various solutions
      are used to improve bond strength of these posts to root dentine. The purpose of
      this study was to evaluate the effect of the different pre-treatments (ethanol,
      ethylene de amine tetra acetic acid [EDTA] and EDTA + ethanol) on the bond
      strength of adhesively lutted tooth colored fiber post. MATERIALS AND METHODS:
      Forty-eight human anterior teeth (incisor and canine) were selected in this
      experimental study. The species were endodontically treated, and the post-space
      was prepared. The species were randomly divided into four groups of 12 teeth in
      each and were treated as follows: (i) 0.1 M EDTA, (ii) 99.6% ethanol, (iii) 0.1 M
      EDTA followed by 99.6% ethanol and (iv) without any treatment (control). A push
      out test was carried out after 24 h. Each tooth was cut into three 1 mm-thick
      sections. Fracture type was assessed using stereomicroscope. The data were
      analyzed by one way-ANOVA followed by Scheffe post-hoc test at P = 0.05. RESULTS:
      Almost, in EDTA and (EDTA + ethanol) every sample failed at the interface between
      post and lutting cement. Predominant failure mode in ethanol and control group
      was mixed failure. The surface treatment methods did not have any significant
      effect (P > 0.05) on any group but EDTA group had the highest bond strength.
      CONCLUSION: Surface treatment with (ethanol, EDTA, and EDTA + ethanol) does not
      significantly appear to be effective in improving the bond strength of fiber
      posts into root dentine. The highest bond strength was observed in EDTA group and
      the lowest in the control group.

PMID- 24130595
TI  - Subscriber identity module: A new method for denture identification.
AB  - This article describes a technique for placing subscriber identity module into a
      complete denture. The cards stores information in the form of text messages and
      contacts which is easily accessible with all mobile devices, thus enabling
      quicker identification. 

PMID- 24130596
TI  - A rare case of hidebound disease with dental implications.
AB  - Systemic sclerosis (also called as Scleroderma or hidebound disease) is a chronic
      sclerotic disease of unknown etiology which causes diffuse, increased deposition
      of extra cellular matrix in connective tissue with vascular abnormalities,
      resulting in tissue hypoxia. The disease is characterized by diffuse fibrosis;
      degenerative changes; and vascular abnormalities in the skin (scleroderma),
      articular structures, and internal organs. Aesthetic and facial dysfunctions are
      followed by important oral and facial manifestations. Most oral manifestations
      begin with tongue rigidity and facial skin changes. Bone resorption of mandibular
      angle and widening of periodontal ligament space on periapical radiographs are
      important radiological findings. Other systemic changes include the involvement
      of internal organs, which lead to serious complications as well as disorders in
      the cardiac muscle and Raynaud?s phenomenon. This is a case report of 30-year-old
      female patient with the classical features of this disease. This case is reported
      for its rarity and variable expressivity. The main aim of this article is to
      describe thorough presentation of the case report, various forms of scleroderma,
      pathogenesis, oral, extraoral, periodontal manifestations of scleroderma, and its
      treatment options. A brief review of the literature, focusing on dental
      alterations is also presented. 

PMID- 24130597
TI  - A comprehensive oral and dental management of an epileptic and intellectually
      deteriorated adolescent.
AB  - Epilepsy along with intellectual deterioration and other neurological disorders
      can have social, physical, and psychological consequences, especially, when they
      begin in childhood. Moreover, the seizure episode along with mental deterioration
      may compromise the oral and dental care resulting in numerous decayed teeth. This
      report presents the case history of an adolescent with poor oral hygiene and
      numerous decayed teeth. This report also presents the comprehensive endodontic,
      surgical, and prosthodontic management of epileptic mentally challenged patient
      in the dental office. Epilepsy along with intellectual deterioration and other
      neurological disorders can have social, physical, and psychological consequences,
      especially, when they begin in childhood. Moreover, the seizure episode along
      with mental deterioration may compromise the oral and dental care resulting in
      numerous decayed teeth. This report presents the case history of an adolescent
      with poor oral hygiene and numerous decayed teeth. This report also presents the
      comprehensive endodontic, surgical, and prosthodontic management of epileptic
      mentally challenged patient in the dental office. 

PMID- 24130598
TI  - Eagle's syndrome: A rare case of young female.
AB  - Eagle's syndrome is a condition that causes pain in the Craniofacial and cervical
      region of the neck. Symptoms related to the Eagle's syndrome may be confused with
      the variety of neuralgias, oral, dental and temporomandibular joint (TMJ)
      conditions. In this paper, a case of the very young female suffering with the
      difficulty in swallowing and recurrent dull pain in the throat with restriction
      of the movement of head to the left side was presented. A thorough past medical
      and dental history, extra oral and intra oral examination coupled with the
      panoramic radiographic interpretation were used to diagnose Eagle's syndrome. 

PMID- 24130599
TI  - Heterogeneity and new epitopes of hepatitis C virus genotype 4.
AB  - BACKGROUND: Hepatitis C virus (HCV) was found to have a major role in human liver
      disease by its ability to face the host-cell defenses and the immune system.
      Heterogeneity of HCV was the key for its adaptation to its host and represented a
      significant hurdle for the development of both effective vaccines as well as for
      novel therapeutic interventions. OBJECTIVES: Due to the heterogeneity of HCV
      virus because of both high replication and high mutation rate in vivo, this study
      was conducted to analyze different isolates of Egyptian patients of genotype 4,
      of the most mutant regions of the virus (E1 and E2) as they played an important
      role in viral persistence by escaping from the immune system of the host body.
      PATIENTS AND METHODS: This study was conducted through PCR amplification of E1
      and E2 regions, sequencing and phylogenetic analysis, calculating synonyms and
      non-synonyms substitutions, finding the possible glycosylation sites and
      different epitope domains. RESULTS: The present work figured out that the
      heterogeneity of the quasispecies of our local strains 4a was high showing up 15%
      diversity. This study also showed four glycosylation sites that play an important
      role in the entry of the virus and protein folding. Besides, different epitpoes
      were identified in different regions of the E1 and E2 domains; a finding which
      would help in determining the neutralizing and non- neutralizing antibodies.
      CONCLUSIONS: This study would help in understanding the driving forces of genetic
      diversity and would be fundamental for representing potential candidate targets
      for antibodies and the development of vaccine trials.

PMID- 24130600
TI  - Plasma zinc level in hepatitis C patients with or without Beta thalassemia major;
      is there any difference?
AB  - BACKGROUND: Zinc deficiency has been reported frequently in hepatitis C patients
      in the literature. Furthermore, a decrease in zinc level has been shown in beta
      thalassemia major as well. Iranians consume a large amount of phytate in their
      regimens which can bind with zinc and decrease its gastrointestinal absorption.
      OBJECTIVES: This study was designed to determine plasma zinc level in an Iranian
      sample with the diagnosis of hepatitis C with or without concomitant beta
      thalassemia major. PATIENTS AND METHODS: Between April 2011 and April 2012,
      plasma zinc level was determined via atomic absorption method, in 130 hepatitis C
      patients with or without beta thalassemia major in a known referral center of
      hepatic diseases in Tehran, Iran. RESULTS: Mean +/- standard deviation (SD) of
      plasma zinc levels was determined as 0.78 +/- 0.22 mg/L. Also zinc level was 0.76
      +/- 0.19 mg/L and 0.80 +/- 0.24 mg/L in thalassemic and non thalassemic patients,
      respectively. T-test analysis showed that there is no significant difference
      between these two groups regarding plasma zinc level (P = 0.235). CONCLUSIONS: It
      is concluded that zinc level of studied patients is less than which is reported
      in normal Iranian population. Moreover, there is not a significant difference in
      plasma zinc levels between thalassemic and non thalassemic patients and it seems
      to be a common problem in both ones. Addition of zinc supplement may be
      recommended in both groups in order to optimize the nutritional support and
      probably improve the treatment response.

PMID- 24130601
TI  - The effect of co-enzyme q10 on acute liver damage in rats, a biochemical and
      pathological study.

PMID- 24130602
TI  - More on current evidences on probiotics as a novel treatment for non-alcoholic
      Fatty liver disease.

PMID- 24130603
TI  - Habit Reversal versus Object Manipulation Training for Treating Nail Biting: A
      Randomized Controlled Clinical Trial.
AB  - OBJECTIVE: This is a parallel, three group, randomized, controlled clinical
      trial, with outcomes evaluated up to three months after randomization for
      children and adolescents with chronic nail biting. The current study investigates
      the efficacy of habit reversal training (HRT) and compares its effect with object
      manipulation training (OMT) considering the limitations of the current
      literature. METHOD: Ninety one children and adolescents with nail biting were
      randomly allocated to one of the three groups. The three groups were HRT (n =
      30), OMT (n = 30), and wait-list or control group (n = 31). The mean length of
      nail was considered as the main outcome. RESULTS: The mean length of the nails
      after one month in HRT and OMT groups increased compared to the waiting list
      group (P < 0.001, P < 0.001, respectively). In long term, both OMT and HRT
      increased the mean length of nails (P < 0.01), but HRT was more effective than
      OMT (P < 0.021). The parent-reported frequency of nail biting did show similar
      results as to the mean length of nails assessment in long term. The number of
      children who completely stopped nail biting in HRT and OMT groups during three
      months was 8 and 7, respectively. This number was zero during one month for the
      wait-list group. CONCLUSION: This trial showed that HRT is more effective than
      wait-list and OMT in increasing the mean length of nails of children and
      adolescents in long terms.

PMID- 24130604
TI  - Reliability and validity of the ''personal well-being index- cognitive
      disability'' on mentally retarded students.
AB  - OBJECTIVE: Having a good quality of life has always been desirable for humans,
      and the concept of a good life and the ways of achieving it have become important
      over the years. Personal wellbeing is the mental component of quality of life.
      Thus, the current study was conducted to assess the reliability and validity of
      the ''Personal Well-Being Index- Cognitive Disability'' on mentally retarded
      students. METHOD: 200 mentally retarded students in north districts of Tehran
      (districts 1, 2 and 3) were selected by systematic random sampling. The collected
      data using Personal Well-Being Index- Cognitive Disability was analyzed by
      Cronbach's alpha coefficient for internal consistency and linear multivariate
      regression for construct validity. RESULTS: Results confirmed the reliability and
      validity for the Personal Well-Being Index- Cognitive Disability in mentally
      retarded students of exceptional schools. Studying the internal consistency of
      seven items showed that all the items were correlated with the total score and
      their scores averages were similar to each other. This indicates that the test's
      questions have reliability with regard to evaluation of a common feature and
      results showed Personal Well-Being Index- Cognitive Disability had the most
      extensive coverage of construct validity. CONCLUSION: Personal Well-Being Index-
      Cognitive Disability scale could be applied to measure personal wellbeing in
      mentally retarded students.

PMID- 24130605
TI  - Effects of zinc supplementation in patients with major depression: a randomized
      clinical trial.
AB  - OBJECTIVE: Major depression is a mood disorder that causes changes in physical
      activity, appetite, sleep and weight. Regarding the role of zinc in the pathology
      of depression, the present study was aimed to investigate the effects of zinc
      supplementation in the treatment of this disease. METHODS: This study was a
      double-blind randomized clinical trial. Forty four patients with major depression
      were randomly assigned to groups receiving zinc supplementation and placebo.
      Patients in Zinc group received daily supplementation with 25 mg zinc adjunct to
      antidepressant; Selective Serotonin Reuptake Inhibitors (SSRIs), while the
      patients in placebo group received placebo with antidepressants (SSRIs) for
      twelve weeks. Severity of depression was measured using the Beck Depression
      Inventory at baseline and was repeated at the sixth and twelfth weeks. ANOVA with
      repeated measure was used to compare and track the changes during the study.
      RESULTS: The mean score of Beck test decreased significantly in the zinc
      supplement group at the end of week 6 (P < 0.01) and 12 (P < 0.001) compared to
      the baseline. The mean score of Beck Depression Inventory reduced significantly
      compared to the placebo group at the end of 12th week (P < 0.05). CONCLUSION: The
      results of the present study indicate that zinc supplementation together with
      SSRIs antidepressant drug improves major depressive disorders more effectively in
      patients with placebo plus antidepressants (SSRIs).

PMID- 24130606
TI  - Assessing the validity and reliability of the farsi version of inventory drug
      taking situations.
AB  - OBJECTIVE: Inventory Drug-Taking Situations (IDTS) is a universal instrument used
      to determine high-risk situations resulting in drug abuse. The aim of this study
      was to translate this questionnaire to Farsi, and to assess its validity and
      reliability by applying it to Iranian drug users. METHODS: As a psychometric
      study, 300 drug users participated in a treatment program in National Center of
      Addiction Studies filled in a version of Inventory of Drug Taking Situations. We
      assessed face and content validity, internal consistency, and reliability based
      on the completed questionnaires, using test-retest method and confirmatory factor
      analysis. RESULTS: Internal consistency analysis confirmed that all subscales of
      IDTS were reliable (Cronbach alpha was ranging from 0.7 to 0.81). Analyses
      indicated that each of the subscales was unifactorial; however, unpleasant
      emotions had a second eigenvalue that was nearly large enough to be a second
      factor. Confirmatory factor analysis was used to test the fit of the data to the
      original version of IDTS. Based on goodness of fit indices, we found that all
      factors were fitted (chi2/df = 1.43, GFI = 0.98, RMSEA = 0.038). The test-retest
      reliability was satisfactory(r > 0.6). CONCLUSION: The Farsi version of Inventory
      of Drug Taking Situations was shown to be a valid and reliable instrument to
      apply in clinical and research settings in Iran.

PMID- 24130607
TI  - Serotonin Transporter Polymorphism (5-HTTLPR) and Citalopram Effectiveness in
      Iranian Patients with Major Depressive Disorder.
AB  - OBJECTIVE: Several studies have implicated the 5-HTTLPR polymorphism in treatment
      outcomes of selective serotonin re-uptake inhibitors in patients with major
      depression. The aim of this study was to examine the association between
      polymorphism in the serotonin transporter gene and citalopram effectiveness in
      Iranian patients suffering from major depressive disorder (MDD). METHODS: The
      sample consisted of 104 patients, with Fars ethnic background, who were diagnosed
      according to DSM-IV-TR criteria. Beck Depression inventory was used to evaluate
      the severity of the symptoms during the follow-up, and to determine clinical
      response of the patients at 4th and 8th week, respectively. RESULTS: Our results
      showed a correlation between the genotype and response to antidepressant drug
      citalopram, (odds ratios for L/S and L/L were 3.90 (95 percent CI: 1.29- 11.80)
      and 1.90 (95 percent CI: 0.72-5.08), respectively). CONCLUSION: In conclusion,
      our results reveal that genetic variation of serotonin transporter is involved in
      clinical remission of major depressive episodes in Iranian patients after
      citalopram treatment.

PMID- 24130608
TI  - Dependence of the geriatric depression on nutritional status and anthropometric
      indices in elderly population.
AB  - OBJECTIVE: Malnutrition and depression are highly prevalent in the elderly and
      can lead to unfavorable outcomes. The aims of the current study were to determine
      the association between malnutrition and depression and also to find any
      correlation of depression with some anthropometric indices in free living
      elderly. METHOD: In this cross-sectional study, 337 elderly subjects (193
      females) were selected using cluster sampling. Depressive symptoms and
      nutritional status were determined by the Geriatric Depression Scale (GDS) and
      the Mini-Nutritional Assessment (MNA) scores questionnaires, respectively.
      Anthropometric indices were measured all in standard situations. Chi squared test
      and t-test were used when necessary. Pearson correlation coefficients were
      calculated for linear relations between variables. RESULTS: Of all the total
      subjects, 43.62% were depressed; and of whom, 48.01% were malnourished or at risk
      of malnutrition. GDS had a significant negative dependence with the MNA for the
      entire sample (r=-0.58, p <0.0001). However, there was no significant correlation
      between age and GDS or MNA scores. Moreover, the mean GDS scores differed
      significantly between men and women (p <0.05), and women were more depressed than
      men (27.9% vs. 15%, respectively). The elderly subjects living in urban areas
      were more depressed than those living in rural areas (39.46% vs. 3.85%
      respectively). CONCLUSION: The results of the present study revealed a high
      prevalence of depression and malnutrition among old subjects. Moreover,
      depression was associated with worsening of nutritional status. The mechanism of
      this association needs further study.

PMID- 24130609
TI  - Drug Craving Terminology among Opiate Dependents; A Mixed Method Study.
AB  - OBJECTIVE: Drug craving is defined as an urge to continue substance abuse. Drug
      dependents use different terms to express their subjective feeling of craving.
      This study was an attempt to generate an understanding of craving terminology
      among different groups of Persian speaking Iranian opiate dependents. METHOD:
      Terms used for the meaning of drug craving were listed by 36 ex-opiate dependents
      in focus group discussion meetings in the first phase of the study. These terms
      were composed from Craving Terms Questionnaire. In the second phase, 120 subjects
      in 3 groups of opiate dependents and a group of Current Opiate Abusers rated
      usage frequency of each term in the questionnaire under a Twelve-Step Program,
      Methadone Maintenance, and Other Abstinence-based Programs. RESULTS: Eighty nine
      terms were categorized in stimulation and triggering, attention bias and
      obsession, decision making difficulty, information processing impairment,
      withdrawal induction, drug euphoric experience, mental urge, motor control
      problem, negative valancing and stigmatizing. Terms for the three categories of
      mental urge, attention bias and obsession and motor control problem were used
      more than others. Patients in Methadone Maintenance Treatment (MMT) group used
      different categories of craving terms in comparison to other groups. Abstinent
      cases reported higher total score for craving terms in comparison to other groups
      in Twelve-Step Program and other abstinence-based programs. CONCLUSION: Each
      craving-related term is associated with some aspects of the multidimensional
      concept of craving. A drug-craving thesaurus could provide a better understanding
      of craving nature from a drug dependent point of view. There are differences
      among abstinence vs. maintenance based treated opiate dependents in using craving
      terms. Addiction therapists will benefit from accessing drug dependents' lexicon
      to assess and create therapeutic alliance with their clients.

PMID- 24130610
TI  - An 18-month Follow-up of Anger in Female Karate Athletes.
AB  - OBJECTIVE: The aim of this study was to evaluate changes of anger scores in
      female karate athletes during 18 months, and to compare anger scores in
      adolescents who continue or stop training karate. METHOD: The sample consisted of
      18 female elite karate athletes, practicing modern style of karate. To measure
      anger and its subscales, participants were asked to complete "Adolescent Anger
      Rating Scale" (AARS) questionnaire in both stages of the study. Athletes were
      divided in to two groups of "stayer" (n=12) and "quitter" (n=6) if they continued
      practicing karate or stopped it, respectively. In order to study the changes of
      anger score with time, paired T test was used. RESULTS: In analysis of changes in
      anger scores with time, there was a statistically significant increase in
      instrumental anger (p=0.001) and non-significant increase in other anger scores
      among 14-year-old girls who continued practicing karate. CONCLUSION: Increased
      instrumental anger in female karate athletes could be due to the impact of
      participation in a combative sport. However, the results should be interpreted
      cautiously due to limitations of the study.

PMID- 24130611
TI  - A review of surgically treated patients with obstruction after stenting in the
      femoropopliteal artery region.
AB  - In this study, we retrospectively reviewed 36 cases that required surgical
      treatment in the femoropopliteal regions (46 regions) because of the development
      of obstructions after stent placement in these patients. Of the 46, stents were
      placed in 37 involved regions (80.4%) that included the common femoral and
      popliteal arteries; such as the common femoral, entire length of superficial
      femoral, or popliteal arteries, and the anastomosis site created during
      femoropopliteal (prosthetic graft) bypass surgeries (Group A). In contrast, 9
      involved regions (19.6%) did not include the common femoral or popliteal
      arteries; the stents were primarily localized in the superficial femoral artery
      (Group B). Symptoms of stent occlusion were more severe in the former group of
      patients, who subsequently required peripheral artery bypass surgery. These
      results indicate that placement of stents in the common femoral artery and
      popliteal arteries should be avoided. (English translation of J Jpn Coll Angiol
      2012; 52: 19-23). 

PMID- 24130612
TI  - Respiratory and hemodynamic changes in patients with chronic thromboembolic
      pulmonary hypertension 1 year after pulmonary endarterectomy.
AB  - We reviewed the results of thromboembolectomy, which was performed for the
      treatment of chronic thromboembolic pulmonary hypertension (CTEPH), 1 year after
      the operation. We obtained hemodynamic and respiratory data of 60 patients from
      the 112 patients who were operated at our institute. The hemodynamic parameters
      such as mean pulmonary arterial pressure (PAP), pulmonary vascular resistance
      (PVR), and cardiac index (CI) were significantly improved after the operation,
      and this improvement of pulmonary hemodynamics persisted even a year after the
      operation. A significant improvement in gas exchange was observed immediately
      after the operation and a further elevation in the partial pressure of oxygen in
      arterial blood (PaO2) was observed 1 year after the operation. (English
      Translation of J Jpn Coll Angiol 2012; 52: 53-58). 

PMID- 24130614
TI  - Usefulness of acceleration time for internal carotid artery origin stenosis.
AB  - Calcification of the internal carotid artery (ICA) hinders accurate evaluation of
      the stenosis by conventional ultrasonography due to acoustic shadow. We examined
      the relationship between acceleration time (AcT) and ICA origin stenosis. One
      hundred thrity seven samples (266 vessels) that enforced duplex ultrasonography
      in our hospital were targeted. The results have shown that there is a significant
      relationship between AcT and stenosis. AcT of more than 110 msec suggests that
      the stenosis is more than 60% by the North American Symptomatic Carotid
      Endarterectomy Trial (NASCET) method. AcT is thought to be useful for the
      diagnosis of ICA stenosis with calcification. (English Translation of J Jpn Coll
      Angiol 2011; 51: 365-371). 

PMID- 24130613
TI  - Cardiac sympathetic activity assessed by heart rate variability indicates
      myocardial ischemia on cold exposure in diabetes.
AB  - Measurement of heart rate variability (HRV) is a non-invasive technique that can
      be used to investigate functioning of the autonomic nervous system, especially
      the balance between sympathetic and vagal activities. It is reported that
      dilatation of coronary microcirculation by augmentation of sympathetic nerve
      activity (SNA) caused by cold exposure was impaired in diabetes. The question of
      whether or not SNA in HRV could respond to coronary ischemia was evaluated by
      cold exposure in diabetic rats. It was found that diabetes with weight loss
      significantly increased SNA both in baseline and cold exposure, compared with
      control. A correspondence was also found with coronary ischemia. It can be
      concluded that measurement of HRV may provide useful information regarding the
      coronary risk of cold exposure in diabetes. (English translation of J Jpn Coll
      Angiol 2012; 52: 295-301). 

PMID- 24130615
TI  - Evaluation of the paramalleolar bypass for critical limb ischemia patients on
      hemodialysis with diabetes mellitus and chronic renal failure.
AB  - OBJECTIVE: To assess the influence of diabetes mellitus (DM) and end-stage renal
      failure on hemodialysis (HD) on the healing time of tissue lesions and blood flow
      to the foot following a paramalleolar bypass in patients with critical limb
      ischemia (CLI). METHODS: Consecutive patients with CLI and tissue loss (24 limbs)
      were followed up retrospectively after paramalleolar bypass, and the healing time
      of tissue lesions, graft patency, limb salvage and survival rates were analyzed.
      The blood flow to the foot was assessed by skin perfusion pressure (SPP) pre- and
      postoperatively. The delta SPP was calculated as the difference between the SPP
      before and after bypass. The patients were divided into 3 groups: diabetic (DM, n
      = 9); diabetic and end-stage renal failure on hemodialysis (HD, n = 10); or
      neither (n = 5). RESULTS: A total of 15 dorsal and 9 plantar artery bypasses were
      performed. The median follow-up was 7.3 months (range, 1-18 months). No patients
      required major amputations, and all tissue lesions healed. The mean duration to
      complete tissue healing of the DM, HD and neither groups was 2.2, 2.5 and 1.2
      months, respectively, was and these were not statistically significant. A
      significant improvement in the delta SPP after paramalleolar bypass was observed
      in the neither group compared with both the DM and HD groups. CONCLUSION: Blood
      flow to the foot was not sufficiently improved in CLI patients with DM and HD,
      despite paramalleolar bypass. This may be the cause of the prolonged tissue
      healing duration of CLI patients with DM and HD. (English Translation of Jpn J
      Vasc Surg 2012; 21: 91-95).

PMID- 24130616
TI  - Innovative application of available stent grafts in Japan in aortic aneurysm
      treatment-significance of innovative debranching and chimney method and coil
      embolization procedure.
AB  - OBJECTIVE: We here describe our experience with innovative uses of these devices.
      PATIENTS AND METHODS: We reviewed treatment outcomes of 310 endovascular
      abdominal aortic repair (EVAR) and 83 thoracic endovascular aortic repair (TEVAR)
      cases performed between August 2007 and February 2012. We separately assessed
      results in elderly and high-risk patients who had a novel procedure. This group
      included 94 patients who underwent EVAR with IIA embolization, 10 patients who
      had EVAR and a renal artery chimney procedure for a short aortic neck, 20
      patients who had two de-branching TEVAR or Chimney method for thoracic aortic
      aneurysms (TAA) and 3 patients who had debranching TEVAR for thoracic abdominal
      aortic aneurysms (TAAA). RESULTS: Of the 393 patients given stent grafts (SGs), 3
      (0.8%) died in the hospital, including 1 patient with pneumonia who underwent
      EVAR and IIA embolization and 1 patient with a cerebral infarction who had TEVAR.
      Four patients (4.3%) who were treated with EVAR with internal iliac artery (IIA)
      embolization presented with residual buttock claudication 6 months
      postoperatively, and 3 patients (3.2%) had onset of ischemic enteritis; however,
      in all 7 patients, the condition resolved without additional intervention. In the
      10 patients who had EVAR and a renal artery chimney method, the landing zone (LZ)
      was <=10 mm, but neither endoleak nor renal artery occlusion was observed
      perioperatively or during midterm follow-up. Of the 20 patients who had a 2
      debranching TEVAR, including 9 in whom the chimney method was used with the LZ in
      zone 0, 1 (5%) had a residual endoleak. In 3 patients with TAAA, we used SGs to
      cover 4 abdominal branches and bypassed the visceral artery; the outcomes were
      good, with all patients being ambulatory at hospital discharge. CONCLUSION: Among
      innovative SGs treatments, the debranching procedure and the chimney method using
      catheterization and the coil-embolization technique provided good outcomes, as
      used in addition to surgical procedures. Aortic aneurysm treatment will become
      increasingly noninvasive with the continuing development of more innovative ways
      to use the SGs currently available in Japan. (English Translation of Jpn J Vasc
      Surg 2012; 21: 165-173).

PMID- 24130617
TI  - The effect of short saphenous vein stripping in patients with deep venous reflux.
AB  - OBJECT: We assessed whether or not deep venous reflux (DVR) improved after short
      saphenous vein (SSV) stripping was performed in patients with SSV reflux and DVR.
      MATERIALS AND METHODS: Sixty-eight patients with SSV reflux who underwent SSV
      striping every Monday between 2008 and 2011 at Ryougoku Ashino Clinic were
      enrolled in this study. Forty-six of the 68 patients were selected for the
      analysis because they underwent duplex ultrasound examinations before and after
      the operation. The DVR was classified into four categories: type 0, no reflux;
      type I, reflux in popliteal vein; type II, reflux from popliteal vein to the
      middle of the superficial femoral vein (SFV) and type III, reflux from the
      popliteal vein to the SFV. RESULTS: There were 23, 13, 2 and 8 patients with type
      0, I, II, III before operation, respectively. There were 33, 8, 1, 4 patients
      with type 0, I, II, III after operation, respectively. There were no changes in
      29 patients, improvement in 15 and new DVR in three (type 0 to I). CONCLUSION:
      SSV stripping is feasible in patients with DVR and the DVR might not be
      deteriorated even though that is performed.

PMID- 24130618
TI  - Current status of patients with buerger disease in Japan.
AB  - THE PREVALENCE AND CLINICAL CHARACTERISTICS OF JAPANESE PATIENTS WITH BUERGER
      DISEASE (THROMBOANGIITIS OBLITERANS: TAO) were analyzed based on the Ministry of
      Health, Labour and Welfare (MHLW) database in 2009. A total of 129 new patients
      and 3639 patients in follow-up were selected according to the clinical criteria
      of TAO. The current number of patients with TAO in Japan is estimated at about
      4000. The clinical course is relatively favorable, and the rates of limb
      morbidity and mortality were not completely discouraging. 

PMID- 24130619
TI  - Renal dysfunction on admission as a predictor for in-hospital mortality of
      patients with stanford type B acute aortic dissection.
AB  - Stanford type A and open false lumen are accepted predictors for in-hospital
      mortality in patients with acute aortic dissection (AAD). However, the
      association of renal dysfunction on admission with in-hospital mortality is not
      well known. The aim of this study was to investigate the prognostic value of
      renal dysfunction in patients with AAD. A total of 250 patients with type B AAD
      admitted to our institution between January 2003 and August 2011 were enrolled in
      this study. In multivariate logistic regression analysis, the significant
      predictors of in-hospital mortality were age (odds ratio [OR] 1.575, 95%
      confidence interval [CI] 1.078-2.864, p = 0.024), maximum aortic diameter
      measured by an initial computed tomography (CT) (OR 1.740, 95% CI 1.029-2.940, p
      = 0.039), decreased enhancement of kidney (OR 7.716, 95% CI 2.335-25.501, p =
      0.001) and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m(2) on
      admission (OR 2.782, 95% CI 1.062-7.283, p = 0.037). In conclusions the results
      identified a renal dysfunction on admission as the independent predictor of in
      hospital mortality in type B AAD. Further investigations are needed to evaluate
      therapies and strategies for decreasing the deterioration of renal function to
      improve in-hospital mortality in patients with AAD. 

PMID- 24130620
TI  - Risk factors affecting survival after surgical repair of ruptured abdominal
      aortic aneurysm.
AB  - PURPOSE: The purpose of this study is to identify the risk factors affecting the
      high mortality rates associated with the treatment of ruptured abdominal aortic
      aneurysm (AAA). METHODS: In this retrospective study, the subjects consisted of
      105 patients who underwent repair of ruptured AAA at our institution from
      December 1984 to March 2012. We compared the patients of ruptured AAA in survival
      group with those in death group to evaluate the clinical factors in ruptured AAA
      mortality. RESULTS: The operative and in-hospital mortality of ruptured AAA
      patients was 22.9% compared with 1.9% for that of non-ruptured AAA patients. The
      mean hemoglobin level was significantly lower in death group than in survival
      group. Intraoperative bleeding volume was significantly higher in death group
      than in survival group. Cox proportional hazard analysis showed that level 3 or 4
      according to the Rutherford classification, preoperative hemoglobin level of less
      than 9.0 g/dl, intraoperative blood loss volume of more than 3000 ml,
      postoperative bowel ischemia and class 3 or 4 according to the Fitzgerald
      classification were significantly associated with high mortality. CONCLUSION:
      These findings showed that every effort to maintain preoperative hemodynamic
      stability reduce volumes of blood loss in operation, and to minimize
      postoperative deterioration of organ functions would be essential to improve
      patient survival.

PMID- 24130621
TI  - Surgical treatment of aneurysms in the upper limbs.
AB  - OBJECTIVE: The purpose of this study was to review the experience of aneurysms in
      the upper limbs treated with surgery and assess the outcomes. MATERIALS AND
      METHODS: This study retrospectively reviewed the medical records of five patients
      with upper extremity aneurysms treated with surgical resection at Tokyo Medical
      and Dental University Hospital between March 2000 and February 2012. These
      patients were treated with excision surgery either with or without reconstructive
      surgery. RESULTS: Two of the five patients were males and three were females with
      a mean age of 52 years (age range: 25-72 years). We treated 2 brachial, 2 ulnar,
      and 1 radial aneurysms. All aneurysms were excised, and two patients had
      reconstructive surgery. Three patients had false aneurysms, which included an
      ulnar artery aneurysm diagnosed as angiolymphoid hyperplasia with eosinophilia.
      During follow-up period, all grafts were clinically patent, and no cases had
      recurrent lesions. No patients had ischemic symptoms or any other postoperative
      complications. CONCLUSION: Arterial aneurysms of the upper extremities are
      uncommon, and were most commonly caused by non-traumatic etiology in this series.
      These aneurysms were excised with or without reconstructive surgery, because of
      the fear of rupture and embolization. Revascularization can be performed
      selectively.

PMID- 24130622
TI  - Early experience with fenestrated stent grafts for treatment of juxtarenal aortic
      aneurysm.
AB  - BACKGROUND: Fenestrated endovascular abdominal aneurysm repair (FEVAR) using
      branched arteries devices for visceral arteries is increasingly being used for
      the repair of juxtarenal aortic aneurysms (JAAs) in Europe, United States,
      Australia, New Zealand, and Asia. This study aimed to evaluate the technical
      feasibility and short-term results of FEVAR in treating JAAs in Japanese
      patients. METHODS AND RESULTS: FEVAR with Cook fenestrated stent-graft (Cook
      Medical Inc., Bloomington, Indiana, USA) was performed for 5 patients at high
      risk for open repair of JAA. Seventeen visceral vessels were successfully
      accommodated with 12 fenestrations, and five visceral arteries with four scallops
      with a loss of renal artery. In one case, a type III endoleak occurred at a renal
      artery fenestration, and this had disappeared in the 1-month postoperative
      computed tomography (CT). The mean follow-up duration was 8 months. Iliac leg
      occlusion occurred in 1 case, which was treated with thrombectomy and additional
      leg device deployment. All patients had survived at the end of the follow-up
      period and continued their outpatient visits. CONCLUSIONS: Implantation of a Cook
      fenestrated stent-graft incorporating the visceral arteries is technically
      feasible in high-risk Japanese patients with JAA and may be a viable alternative
      to current methods.

PMID- 24130623
TI  - Aneurysm of the tibio-peroneal trunk: case report.
AB  - Behcet's disease is an inflammatory disorder of unknown cause. It's a systemic
      disorder that may affect any system in the body. Vascular system involvement
      occurs in 25%-30%. The case presented here elicits both venous and arterial
      complications of Behcet's disease in the same patient. The patient presented to
      our emergency with signs and symptoms of ruptured tibioperoneal aneurysm that was
      treated both medically and surgically. 

PMID- 24130624
TI  - Occupational true aneurysm of the ulnar artery: a case report of hypothenar
      hammer syndrome.
AB  - A 32-year-old male patient was admitted to the hospital with a pulsing mass of
      the right palm. He was an electrical construction engineer who frequently used a
      screwdriver. Computed tomography (CT) examination revealed a 22- * 30-mm saccular
      aneurysm of the right ulnar artery. The ulnar artery aneurysm was resected, and
      we could perform direct anastomosis of the ulnar artery. The dilated true
      aneurysm was compatible with a traumatic origin. A postoperative enhanced CT
      examination showed smooth reconstruction of the palmar arch. An occupational true
      aneurysm of the ulnar artery could be treated by resection and direct
      anastomosis. 

PMID- 24130626
TI  - A modified technique of intercostal artery implantation for thoracoabdominal
      aortic aneurysm using the tube of the aortic wall.
AB  - We report a modified intercostal artery implantation using the tube of the aortic
      wall alternative to the Crawford inclusion and Carrel Patch techniques for
      thoracoabdominal aortic aneurysm repair. Intercostal and lumbar arteries were
      isolated within a full-thickness excised aortic cuff and tailored into a tube. An
      8-mm limb was sewn to the proximal graft and the aortic cuff tube. The distal
      tube end was sewn to an 8-mm limb and a distal limb was connected to the distal
      graft. Computed tomography (CT) showed no pseudoaneurysms or aneurysmal expansion
      but did show patent intercostal arteries at the implantation site more than 5
      years later. 

PMID- 24130625
TI  - Circumaortic left renal vein associated with juxtarenal abdominal aortic
      aneurysm.
AB  - The patient was an 82-year-old man who was found to have a juxtarenal abdominal
      aortic aneurysm accompanied by a circumaortic left renal vein (CLRV). During
      dissection of the proximal anastomosis site the CLRV was injured, but was
      successfully repaired. A graft implantation was performed below the renal
      arteries. The incidence of CLRV is thought to be rare, however it is found in 7%
      of cadavers donated for anatomy. CLRV may cause unexpected bleeding by
      inadvertent dissection of the abdominal aorta. To prevent unexpected bleeding,
      surgeons should always keep in mind this potential risk when performing surgery. 

PMID- 24130627
TI  - Partial root remodeling on the two sinuses for acute type a aortic dissection
      with right coronary arterial dissection.
AB  - We reported simple partial root remodeling using a graft trimmed twin "U" shape
      for extensive dissection into the right/non-coronary sinuses with acute type A
      aortic dissection with cardiac tamponade, acute myocardial infarction on the
      right coronary artery and aortic regurgitation. After total arch replacement with
      frozen elephant trunk technique for distal dissection, partial root remodeling on
      the non and right coronary sinuses was performed. Postoperative computed
      tomography (CT) showed well shaped Valsalva sinuses and aortic regurgitation
      completely disappeared. This technique might become an alternative procedure for
      aortic dissection severely involving Valsalva sinuses without dilatation on the
      aortic root. 

PMID- 24130628
TI  - Successful Ascending Aorta-Abdominal Aorta Bypass Graft through the Left Thoracic
      Cavity in a Patient with Atypical Coarctation.
AB  - A 67-year-old woman admitted with severe hypertension, atrial fibrillation, and
      dyspnea was found to have hypertension and congestive heart failure due to
      stenosis of the descending aorta. Atypical aortic coarctation was diagnosed.
      Extra-anatomical bypass was performed from the ascending aorta to the terminal
      abdominal aorta and the pulmonary vein was isolated. The graft was arranged to
      pass through the left thoracic cavity from the pericardium via a
      transretroperitoneal approach to the terminal abdominal aorta. Direct contact was
      avoided between the graft and the abdominal organs, and the pressure gradient
      between the ascending aorta and the abdominal aorta was decreased. 

PMID- 24130629
TI  - Two cases of successful inferior mesenteric artery preservation with bare metal
      stent in endovascular iliac artery aneurysm repair.
AB  - During endovascular aneurysm repair, interruption of the inferior mesenteric
      artery (IMA) or internal iliac arteries (IIAs) is thought to be associated with
      postoperative pelvic ischemic complications, including ischemic colitis. However,
      preserving the IIA does not guarantee protection against ischemic colitis. We
      herein report two cases of bilateral common iliac artery aneurysms, which were
      treated with bifurcated stent grafting with bilateral IIA embolization and
      simultaneous IMA stent placement to prevent colonic ischemia. This procedure
      might be effective for both preserving the IMA circulation and preventing
      ischemic colitis. 

PMID- 24130630
TI  - Definition of the rectum and level of the peritoneal reflection - still a matter
      of debate?
AB  - INTRODUCTION: Pathological lesions of the rectum are common and their management
      requires detailed knowledge of pelvic anatomy. There has been considerable debate
      as to the definition of the rectum and the variability of the level of the
      peritoneal reflection. The lack of a clear consensus was proven in the research
      by McCullen et al. regarding the current pattern of practice for the
      investigation of primary rectal cancer by general surgeons. AIM: To carry out
      bibliographic research on the definition of the rectum and level of the
      peritoneal reflection. MATERIAL AND METHODS: A web-based published literature
      search of PubMed, Ovid Medline, Science Direct and Springer was made. RESULTS:
      The paper presents the current definitions of proximal and distal margin of the
      rectum and level of peritoneal reflection based not only on the results of tests
      on cadavers but also on living humans. CONCLUSIONS: The results of tests on
      living humans allow more accurate qualification of patients for local excision,
      which is particularly important for patients with colorectal cancer.

PMID- 24130631
TI  - Endoureterotomy is not a sufficient treatment for intrinsic ureteral
      endometriosis.
AB  - AIM: To investigate whether intrinsic ureteral endometriosis could be managed by
      laser endoureterotomy. MATERIAL AND METHODS: We studied retrospectively 6
      patients with intrinsic ureteral endometriosis who underwent laser
      endoureterotomy and reviewed their clinical data. Pathological sections of them
      have also been studied by immunohistochemistry for expressional levels of
      oestrogen (ER) and progesterone (PR) receptors. Ten sections of normal
      endometrium were included as a control. RESULTS: Five patients had recurrence of
      ureteral stricture within 6 months postoperatively despite hormonal therapy for 3
      to 6 months. One patient had recurrence 8 months after endoureterotomy. Two
      patients had secondary surgery for ureteroureterostomy and pathology confirmed
      recurrence of endometriosis. Immunohistochemistry revealed decreased ER and PR
      expression compared to the control. CONCLUSIONS: Endoureterotomy with hormonal
      therapy may not be suitable for ureteral endometriosis due to inadequate cutting
      and expressional change of ER and PR.

PMID- 24130632
TI  - Nonlesional skin in atopic dermatitis is seemingly healthy skin - observations
      using noninvasive methods.
AB  - INTRODUCTION: Atopic dermatitis (AD) is a chronic and relapsing skin disorder,
      which is characterized by abnormal skin barrier function within the entire skin
      surface. Several noninvasive bioengineering methods have been commonly used to
      quantify disease severity. High-frequency ultrasonography (HF-USG) is an
      important contribution to this field. AIM: To evaluate noninvolved skin during
      the external treatment in relation to involved regions in patients with AD skin
      using noninvasive methods. MATERIAL AND METHODS: Transepidermal water loss
      (TEWL), capacitance and erythema assessment and HF-USG were performed in 55 AD
      patients within 2 regions (involved and uninvolved skin) before and after
      therapy. The clinical severity of the disease process was based on the eczema
      area and severity index (EASI) score. A control group consisting of 15 subjects
      was also included. RESULTS: On the basis of 4 bioengineering methods our study
      revealed that uninvolved skin in AD presents subclinical disturbances and
      significantly changes during therapy. The HF-USG detects inflammation in the
      upper dermis in AD patients in the form of a hypoechoic band, which may also be
      observed to a lesser extent within normal-appearing skin. CONCLUSIONS:
      Nonlesional skin differs significantly from lesional skin in AD and from skin of
      healthy subjects. Noninvasive methods are able to measure subclinical skin
      disturbances within normal-appearing skin, which are not evaluated using standard
      clinical scores. They are objective and may facilitate communication between
      different research groups.

PMID- 24130633
TI  - New comprehensive surgical curriculum of pre-graduate surgical education.
AB  - INTRODUCTION: Surgical education has become one of the most important directions
      in modern surgery evolution. To meet growing need for appropriate training in
      laparoscopic and, even more importantly, classic surgical skills, a curriculum
      involving contemporary tuition methods is needed. Advanced, structuralised
      training, which includes advanced technologies like virtual reality training,
      video coaching and motivative aspects of competition, seems to be important for
      an adequate education programme. MATERIAL AND METHODS: In academic years
      2009/2010 and 2010/2011 the Department of General, Endocrine and Transplant
      Surgery of the Medical University of Gdansk together with the Pomeranian
      Foundation for Progress in Surgery organized 4480 h of training in that area of
      classic (2744) and laparoscopic (1736) skills. Both groups were involved in the
      programme of training in which the two most important aspects were reliable
      evaluation of the results and effective motivation to work. Skill evaluation at
      different stages of the programme were based on completion time and quality
      measurements. Apart from that, at the end of the course, the participants
      completed a questionnaire on their subjective perspective on this innovative
      curriculum, the quality and stability of the skills they obtained. RESULTS: In
      both arms of the programme (laparoscopic and classic) a statistically significant
      improvement was obtained as early as after the second and third sessions in half
      of the exercises. The acquired skills were stable over time, as proved by the
      plateau of completion time achieved in 11 out of 12 exercises. The results of the
      post-training questionnaire revealed that the participants were very satisfied
      with the structuralised form of training and appreciated the motivational role of
      competition. CONCLUSIONS: Contemporary surgical training should be organized as a
      systematic, well-evaluated and goal-oriented programme similar to the one
      proposed by our team. The use of contemporary training aids should be utilized in
      training of every surgical skill, not only laparoscopy. This form of training,
      associated with the component of competition, enables good and stable results to
      be achieved, as well as high satisfaction of trainees.

PMID- 24130634
TI  - Minimally invasive management of pancreatic pseudocysts.
AB  - INTRODUCTION: The laparoscopic and endoscopic approaches to internal drainage of
      pancreatic pseudocysts (PP) are the current minimally invasive management
      options. Indications, and early and late results of endoscopic and laparoscopic
      approaches are being discussed. AIM: To present experience in treatment of PP by
      laparoscopic pseudocystogastrostomy (LPGS) and endoscopic pseudocystogastrostomy
      (EPGS) and to compare results, feasibility and safety. MATERIAL AND METHODS:
      THIRTY PATIENTS UNDERWENT SURGICAL INTERVENTION: 18 patients - LPGS (group I), 12
      - EPGS (group II). Groups were compared by age, gender, pancreatic pseudocysts's
      age, diameter and localization, as well as intraoperative, early and late
      postoperative complications. RESULTS: GENDER DISTRIBUTION, GROUP I: 14 (77.8%)
      men and 4 (22.2%) women, group II: 4 (33.3%) men and 8 (66.7%) women, p = 0.02.
      Average cyst diameter: group I - 149.9 +/-52.1 mm, group II - 119 +/-37.9 mm, p =
      0.07. Average time between diagnosis and operation performance: group I - 12 (3
      60) months, group II - 8 (2-36) months, p = 0.19. Neither in group I nor in group
      II did intraoperative complications occur. Early postoperative complications were
      divided into minor and major. Early minor complications: group I - 2 (11.1%),
      group II - 0, p = 0.5. Early major complications: group I - 0, group II - 2
      (16.7%), p = 0.15. Late postoperative complications: group I - 0, group II - 1
      (8.3%), p = 0.4. In group I there was no case, whereas in II group there was 1
      (8.3%) case of recidivation, p = 0.4. CONCLUSIONS: For selected patients both
      minimally invasive methods are equally safe an effective. For comprehensive
      evaluation of methods prospective trials are needed.

PMID- 24130635
TI  - Single incision laparoscopic surgery - is it time for laboratory skills training?
AB  - INTRODUCTION: With the introduction of new surgical equipment, there is always
      the need for new, more advanced training. The authors try to answer whether the
      use of the newest generation tools has an impact on achieving better results in
      single incision laparoscopic surgery (SILS) technique during the exercises in the
      surgical skills laboratory. MATERIAL AND METHODS: There were 51 participants in
      the study: 44 'novices' and 7 'experts'. All subjects performed the 'advanced
      grasping' exercise according to the FLS programme manual using four types of
      laparoscopic approach including two SILS ports and SILS-dedicated instruments.
      The outcome measures involved task completion time and the number of errors.
      RESULTS: Tasks using straight laparoscopic instruments set together with classic
      three-port access as well as SILS access ports were finished significantly faster
      when compared with SILS-dedicated instruments (p < 0.05). There were no
      significant differences in performance times between the two setups with straight
      instruments (p < 0.05) and both setups with SILS-dedicated instruments,
      irrespective of the use of curved or dynamic articulated tools. Students with no
      previous laparoscopic experience had significantly worse task completion times in
      all tasks in comparison to students with laparoscopic laboratory training and the
      'experts' group. CONCLUSIONS: The use of the straight instruments in the SILS
      technique remain similar to its performance in full triangulation. SILS-dedicated
      instruments paradoxically increase the task completion time irrespective of
      possessed skills. The study showed the necessity of a SILS-dedicated tools
      training programme.

PMID- 24130636
TI  - Laparoscopic adrenalectomy for metachronous ipsilateral metastasis following
      nephrectomy for renal cell carcinoma.
AB  - INTRODUCTION: Although laparoscopic adrenalectomy (LA) is considered as a gold
      standard approach for adrenalectomy, there are minimal data describing options
      and outcomes of LA after previous ipsilateral nephrectomy (PIN). AIM: To describe
      our results in a group of patients who underwent LA after PIN. MATERIAL AND
      METHODS: From August 2004 to October 2012 we performed at our institution 88 LA.
      Of this amount we performed 5 LA for metachronous metastasis of renal cell
      carcinoma (RCC) after PIN. This group was compared to a group without previous
      nephrectomy. RESULTS: The group comprised 4 men (80%) and 1 woman (20%); the mean
      age at the time of surgery was 66.8 +/-8.5 (range: 60-77) years; the mean period
      between nephrectomy and adrenalectomy was 5.2 (range: 1.5-14) years; the
      operating time was longer in patients after PIN for 7 min; the mean blood loss
      was higher by 22 ml; duration of hospitalization was shorter by 1.3 days,
      paradoxically, compared with patients without PIN. There was no need for
      conversion to open surgery and we did not observe any other complications.
      CONCLUSIONS: Laparoscopic adrenalectomy for metastasis of RCC after PIN is a
      technically feasible method in selected patients and it is associated with no
      significant differences in perioperative data in comparison with the group
      without prior nephrectomy. The patients benefit from minimally invasive surgery.
      The performance has required an experienced laparoscopic surgeon.

PMID- 24130637
TI  - One, two or three port appendectomy - a rational approach.
AB  - INTRODUCTION: Laparoscopic appendectomy is a safe and feasible technique accepted
      by many surgeons as the gold standard approach for the treatment of acute
      appendicitis in children. Traditionally laparoscopic appendectomy requires the
      use of three ports. However, surgical techniques with fewer ports have been
      reported. AIM: To evaluate the efficacy of laparoscopic appendectomy in children
      according to the proposed 3-step protocol using one, two or three ports. MATERIAL
      AND METHODS: A total of 100 children with the diagnosis of acute appendicitis
      underwent laparoscopic appendectomy. Patients were treated according to the
      following protocol: transumbilical access with one 10 mm port using the
      laparoscope with working channel. The appendix was mobilized and delivered
      through the umbilical port and tied extracorporeally and removed. If the appendix
      was placed retrocecally or had adhesions, a second port was introduced. The
      appendix was mobilized and finally retrieved from the abdominal cavity through
      the camera port, and resected extracorporeally. In the cases of very short and
      gangrenous appendix and immobile colon, a third port was introduced and totally
      intra-abdominal appendectomy was performed. Patients were evaluated regarding the
      duration of the operation, and operative and postoperative complications.
      RESULTS: During the study period 100 children (58 males, 42 females) had
      laparoscopic appendectomy: 48 children by one-port technique (group I), 27
      children by two-port technique (group II) and 25 children by three-port technique
      (group III). The mean operative time was 33 min (20-55 min) in group I, 39 min in
      group II (23-60 min), and 49 min (30-75 min) in group III. There were no
      intraoperative complications. Wound infections were recorded in 4 (8.3%) patients
      in group I, three (11.1%) in group II and four (16.0%) in group III. One patient
      in group III developed an abdominal abscess managed conservatively. CONCLUSIONS:
      One-port laparoscopic appendectomy is a feasible technique in children. It allows
      48% of children to have the operation. The addition of a second port allows one
      to mobilize the appendix and perform extracorporeal resection in an additional
      27% of cases. These approaches have shorter operative time compared to 3-port
      technique. Laparoscopic extracorporeal appendectomy, especially one-port, is
      found to be cost effective and have excellent cosmetic results.

PMID- 24130638
TI  - NOTES. Study on patients' perspective.
AB  - INTRODUCTION: Rapid development of minimally invasive surgery has led to
      escalation of the demands placed on health care professionals. Nowadays the
      patient is the one to choose where and how she/he wants to be operated on.
      Perioperative and postoperative quality of life is the most common item impacting
      the patients' choice. Laparoscopic surgery is undoubtedly advantageous in several
      applications; however a further improvement of medical services has been
      introduced: the NOTES technique. This novel surgical approach definitively
      eliminates the problem of having scars. Though NOTES is still in the clinical
      trial stage, it might become an alternative for selected procedures soon. At this
      point it is necessary to define the patients' expectations and preferences. AIM:
      To evaluate patients' opinions on the four surgical approaches: open,
      laparoscopic, transvaginal and transgastric. MATERIAL AND METHODS: For this
      purpose a special questionnaire was designed and one hundred randomly selected
      women were asked to complete it. RESULTS: The laparoscopic access was preferable
      in most aspects, closely followed by the transvaginal access. Open and
      transgastric approaches were considered as dangerous and disadvantageous.
      CONCLUSIONS: Currently NOTES is a possible reality of tomorrow for some
      procedures. The transvaginal access was scored as "attractive", "cosmetically
      attractive" and "technologically advanced", as opposed to the transgastric
      access. The fact of manipulation in the intimate region requires thorough
      attention in future NOTES studies. Though the patients currently prefer the
      laparoscopic approach, this study proves that further development of transvaginal
      NOTES technology is acceptable and to some extent desired by the patients.

PMID- 24130639
TI  - Gdansk Hybrid Heartlink Programme (GHHP) - we need to share the experience with
      miniinvasive hybrid procedures in borderline babies.
AB  - The Gdansk Hybrid Heartlink Programme follows the concept of the hybrid
      procedures that combine the advantages of classic surgical operations with
      intraoperative cardiology interventions. With time and our growing experience, we
      found that hybrid methods were especially beneficial in cardiac emergencies in
      borderline babies, who would not meet separate criteria either for surgery or for
      cardiac interventions. Hybrid strategies appeared safe and effective for patients
      with anatomical variants unsuitable either for classic surgical or interventional
      procedures introduced alone. Therefore hybrid treatment seems to be a reasonable
      alternative mainly because of diminished risk of fatal complications. The success
      of a hybrid programme is possible in institutions that improve the spirit of
      cooperation between cardiac surgeons and interventional cardiologists, aimed at
      the common benefit of borderline patients. 

PMID- 24130640
TI  - An easy way to put the spleen into the bag.
AB  - INTRODUCTION: Splenectomy is a therapeutic and diagnostic procedure used in a
      wide range of situations. Laparoscopic splenectomy has become the gold standard
      in some hematological diseases. The laparoscopically removed spleen is placed
      into a surgical bag, a step which is sometimes the most time-consuming part of
      the operation. AIM: To present the method that we employed in laparoscopic
      splenectomy to place the specimen into the bag and extract it in an easier and
      simpler way. MATERIAL AND METHODS: The proximal part of the splenorenal ligament
      is left undivided in the size of one LigaSure cut length to use as a stalk while
      placing the spleen into the surgical bag. The bag is advanced from the inferior
      pole of the spleen toward the superior pole. Only keeping the bag open is
      sufficient to place the spleen into the bag. RESULTS: Recently, me started to put
      the spleen into the bag easily before cutting upper attachment of the spleen
      laparoscopically. So far we applied this procedure in more than eleven cases
      without complication. CONCLUSIONS: Splenectomy is now the gold standard in the
      treatment of hematologic diseases that are resistant to medical treatment or that
      are not amenable to medical treatment because of its complications. Through our
      experience, the method that we describe here easily overcomes one of the most
      unpleasant parts of laparoscopic splenectomy.

PMID- 24130641
TI  - Miniinvasive interventional bridge to major surgical repair of critical aortic
      coarctation in a newborn with severe multiorgan failure.
AB  - We present a case of a severely ill newborn with complex coarctation, multiorgan
      failure and massive oedema, who was treated with emergency stenting of the
      isthmus on the second day of life, which was followed by surgical stent removal
      and repair of the arch on the 29(th) day, after stabilization of his general
      status. Interventional percutaneous direct stent implantation was performed,
      using a coronary stent (Abbott Multi-Link Vision Coronary Stent 3.5 mm/15 mm,
      USA) to cover the area of the aortic isthmus in the newborn. The area from the
      origin of the left subclavian artery to the beginning of the descending thoracic
      aorta beneath the isthmus was widely expanded. Control angiography showed normal
      size of the isthmus without a systolic gradient in the area. In the next 3 weeks
      the boy improved his general status, with normalization of liver and renal
      parameters, as well as resolution of the oedema, and underwent surgery on his
      29(th) day of life. The procedure of stent removal with aortic extended end-to
      end anastomosis was performed without complications, and the infant was
      transferred to general paediatrics for further treatment. The strategy of
      miniinvasive interventional bridge to postpone major surgical repair was
      effective in the presented infant, with positive final results of both
      cardiological intervention and subsequent surgical repair. 

PMID- 24130642
TI  - Endoscopic submucosal dissection of gastric ectopic pancreas.
AB  - Patients with gastric tumors usually present with symptoms of discomfort or pain
      in the epigastrium, regurgitations, nausea, vomiting or melena. Treatment options
      include open and laparoscopic total or partial gastrectomy and recently
      endoscopic mucosal resection. A case of successful endoscopic submucosal
      dissection is described with the unusual pathological finding of heterotopic
      pancreatic tissue forming a gastric tumor. The 67-year-old male patient was
      operated on due to the initial diagnosis of gastro-intestinal stromal tumor of
      the gastric trunk. Two intra-operative biopsies were negative for cancer cells.
      Submucosal endoscopic dissection was performed with IT and Hook knives (Olympus).
      A literature review was performed. The operative time was 180 min with hospital
      stay of 6 days. During the injection of the carmine dye and the air insufflation
      pneumoperitoneum occurred and remained clinically silent during the observation
      period. The pathology result showed a heterotopic pancreatic tissue type 2
      according to Heinrich's classification with microfoci of intestinal metaplasia.
      Preoperative diagnostics of gastric masses might be misleading and such tumors
      not necessarily should be excised. There are several surgical options with
      endoscopic submucosal dissection being probably the safest one and a non
      disabling approach. Patients tolerate that kind of surgery well with good
      postoperative functional outcomes. 

PMID- 24130643
TI  - Robot-assisted right colectomy: surgical technique and review of the literature.
AB  - Following the successful introduction of robotic surgery to the field of urology
      and gynecology, its use gained even more interest among those in the field of
      colorectal surgery. Rectal resection is believed to be among the best suited for
      robotic assistance. In particular, the right hemicolectomy procedure has been
      proposed as a training tool in order to gain clinical experience with the robot.
      This article and attached video demonstrates, in detail, the robot-assisted right
      hemicolectomy, including key landmarks of the procedure. The case presented
      involved a 58-year-old man with an advanced cecal adenocarcinoma. In our
      opinionrobot-assisted right colon resection is a procedure that offers particular
      value for the novice robotic team who is in the beginning stages of their
      colorectal surgery experience. Although no concrete advantages for use of the
      robot in this particular procedure have been demonstrated in the literature,
      because it is a relatively straightforward and simple procedure, it can serve as
      a valuable training tool for the novice robotic surgeon. 

PMID- 24130644
TI  - Initial experience with implantation of novel dual layer flow-diverter device
      FRED.
AB  - Flow-diverting stents can help treat complex and wide-necked cerebral aneurysms.
      The aim of the study was to evaluate initial experiences related to the safety
      and effectiveness of eight aneurysms treated with a new dual layer coverage
      designed flow-diverter device. In 2012 Fred flow-diverter devices were used to
      treat 8 unruptured wide neck (dome-neck ratio <= 1.5) and sidewall aneurysms in 6
      patients. All aneurysms were located in the anterior circulation on the internal
      carotid artery (ICA). In 4 larger aneurysms (> 10 mm) one 3D coil in association
      with Fred was used to reduce potential incidence of postoperative subarachnoid
      haemorrhage (SAH). Dual antiplatelet therapy was administered before the
      procedure and continued for 3 months after it. Clinical parameters, aneurysm
      features and 3-month follow-up angiograms are presented. All 6 patients with 8
      aneurysms were successfully stented with the Fred flow-diverter device and were
      discharged in generally good condition on dual-antiplatelet therapy. No
      complications were related to the procedure. In 5 cases digital subtraction
      angiography (DSA) control examination was performed after 3 months, showing
      complete occlusion of the aneurysms with patency of the parent artery. In 1 case
      thrombosis of the Fred occurred but without any clinical consequences because of
      cross-flow from the other side. Use of the Fred flow-diverter device was
      efficacious in all 8 treated cerebral aneurysms. The system seems to be promising
      as a flow diverter with certain characteristics, which allow for easy delivery
      and implantation. Further clinical evaluation with a larger group of patients is
      needed. 

PMID- 24130664
TI  - Evaluating the significance of paleophylogeographic species distribution models
      in reconstructing quaternary range-shifts of nearctic chelonians.
AB  - The climatic cycles of the Quaternary, during which global mean annual
      temperatures have regularly changed by 5-10 degrees C, provide a special
      opportunity for studying the rate, magnitude, and effects of geographic responses
      to changing climates. During the Quaternary, high- and mid-latitude species were
      extirpated from regions that were covered by ice or otherwise became unsuitable,
      persisting in refugial retreats where the environment was compatible with their
      tolerances. In this study we combine modern geographic range data, phylogeny,
      Pleistocene paleoclimatic models, and isotopic records of changes in global mean
      annual temperature, to produce a temporally continuous model of geographic
      changes in potential habitat for 59 species of North American turtles over the
      past 320 Ka (three full glacial-interglacial cycles). These paleophylogeographic
      models indicate the areas where past climates were compatible with the modern
      ranges of the species and serve as hypotheses for how their geographic ranges
      would have changed in response to Quaternary climate cycles. We test these
      hypotheses against physiological, genetic, taxonomic and fossil evidence, and we
      then use them to measure the effects of Quaternary climate cycles on species
      distributions. Patterns of range expansion, contraction, and fragmentation in the
      models are strongly congruent with (i) phylogeographic differentiation; (ii)
      morphological variation; (iii) physiological tolerances; and (iv) intraspecific
      genetic variability. Modern species with significant interspecific
      differentiation have geographic ranges that strongly fluctuated and repeatedly
      fragmented throughout the Quaternary. Modern species with low genetic diversity
      have geographic distributions that were highly variable and at times exceedingly
      small in the past. Our results reveal the potential for paleophylogeographic
      models to (i) reconstruct past geographic range modifications, (ii) identify
      geographic processes that result in genetic bottlenecks; and (iii) predict
      threats due to anthropogenic climate change in the future. 

PMID- 24130665
TI  - A comparison of morphological and molecular-based surveys to estimate the species
      richness of Chaetoceros and Thalassiosira (bacillariophyta), in the Bay of Fundy.
AB  - The goal of this study was to compare the ability of morphology and molecular
      based surveys to estimate species richness for two species-rich diatom genera,
      Chaetoceros Ehrenb. and Thalassiosira Cleve, in the Bay of Fundy. Phytoplankton
      tows were collected from two sites at intervals over two years and subsampled for
      morphology-based surveys (2010, 2011), a culture-based DNA reference library
      (DRL; 2010), and a molecular-based survey (2011). The DRL and molecular-based
      survey utilized the 3' end of the RUBISCO large subunit (rbcL-3P) to identify
      genetic species groups (based on 0.1% divergence in rbcL-3P), which were
      subsequently identified morphologically to allow comparisons to the morphology
      based survey. Comparisons were compiled for the year (2011) by site (n = 2) and
      by season (n = 3). Of the 34 taxa included in the comparisons, 50% of taxa were
      common to both methods, 35% were unique to the molecular-based survey, and 12%
      were unique to the morphology-based survey, while the remaining 3% of taxa were
      unidentified genetic species groups. The morphology-based survey excelled at
      identifying rare taxa in individual tow subsamples, which were occasionally
      missed with the molecular approach used here, while the molecular methods (the
      DRL and molecular-based survey), uncovered nine cryptic species pairs and four
      previously overlooked species. The last mentioned were typically difficult to
      identify and were generically assigned to Thalassiosira spp. during the
      morphology-based survey. Therefore, for now we suggest a combined approach
      encompassing routine morphology-based surveys accompanied by periodic molecular
      based surveys to monitor for cryptic and difficult to identify taxa. As
      sequencing technologies improve, molecular-based surveys should become routine,
      leading to a more accurate representation of species composition and richness in
      monitoring programs. 

PMID- 24130666
TI  - A-methylacyl-CoA racemase (AMACR) and prostate-cancer risk: a meta-analysis of
      4,385 participants.
AB  - BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR) is a mitochondrial and
      peroxisomal enzyme that is overexpressed in prostate cancer. The aim of this
      study was to confirm and expand the findings that the PCa risk increased in men
      associated with AMACR expression across various geographic regions. METHODS: A
      systematic search of databases was carried out and other relevant articles were
      also identified. Then the meta-analyses were conducted according to the standard
      guidelines. RESULTS: A total of 22 studies with 4,385 participants were included
      on the basis of inclusion criteria. AMACR by IHC was significantly associated
      with increased diagnosis of PCa (OR = 76.08; 95% CI, 25.53-226.68; P<0.00001).
      Subgroup-analysis showed that findings didn't substantially change when only
      Caucasians or Asians (OR = 51.23; 95% CI, 19.41-135.24; P<0.00001) were
      considered. Expression of AMACR by PCR in relation to PCa risk suggested that
      AMACR was associated with PCa (OR = 33.60; 95% CI, 4.67-241.77; P<0.00001). There
      was also no significant publication bias observed. CONCLUSIONS: Our findings
      provide further evidences that the expression of AMACR contribute to PCa risk.
      AMACR protein overexpression was found in prostate cancers, low expression in any
      of the normal tissues or in benign prostatic tissue. AMACR is potentially an
      important prostate tumor marker.

PMID- 24130667
TI  - Obesity and dental decay: inference on the role of dietary sugar.
AB  - OBJECTIVE: To evaluate the relationship of children's obesity and dental decay.
      METHODS: We measured parameters related to obesity and dental decay in 8,275
      4(th) and 5(th) grade Kuwaiti children (average age = 11.36 years) in a cross
      sectional study. First to determine body weight, height, age for computation of
      BMI . Second, to determine numbers of teeth, numbers of fillings and numbers of
      untreated decayed teeth to determine extent and severity of dental disease. From
      these measurements, we computed measures of dental decay in children from four
      body weight categories; obese, overweight, normal healthy weight and underweight
      children. RESULTS: The percentage of children with decayed or filled teeth varied
      inversely with the body weight category. The percentage of decayed or filled
      teeth decreased from 15.61% (n=193) in underweight children, to 13.03% (n=4,094)
      in normal healthy weight children, to 9.73% (n=1,786) in overweight children to
      7.87% (n=2,202) in obese children. Differences between all groups were
      statistically significant. Male children in this population had more dental decay
      than female children but the reduction of tooth decay as a function of BMI was
      greater in male children. CONCLUSIONS: The finding of an inverse obesity-dental
      decay relationship contradicts the obesity-sugar and the obesity-dental decay
      relationship hypotheses. Sugar is well recognized as necessary and sufficient for
      dental decay. Sugar is also hypothesized to be a leading co-factor in obesity. If
      the later hypothesis is true, one would expect dental decay to increase with
      obesity. This was not found. The reasons for this inverse relationship are not
      currently clear.

PMID- 24130668
TI  - Super-resolution imaging strategies for cell biologists using a spinning disk
      microscope.
AB  - In this study we use a spinning disk confocal microscope (SD) to generate super
      resolution images of multiple cellular features from any plane in the cell. We
      obtain super-resolution images by using stochastic intensity fluctuations of
      biological probes, combining Photoactivation Light-Microscopy (PALM)/Stochastic
      Optical Reconstruction Microscopy (STORM) methodologies. We compared different
      image analysis algorithms for processing super-resolution data to identify the
      most suitable for analysis of particular cell structures. SOFI was chosen for X
      and Y and was able to achieve a resolution of ca. 80 nm; however higher
      resolution was possible >30 nm, dependant on the super-resolution image analysis
      algorithm used. Our method uses low laser power and fluorescent probes which are
      available either commercially or through the scientific community, and therefore
      it is gentle enough for biological imaging. Through comparative studies with
      structured illumination microscopy (SIM) and widefield epifluorescence imaging we
      identified that our methodology was advantageous for imaging cellular structures
      which are not immediately at the cell-substrate interface, which include the
      nuclear architecture and mitochondria. We have shown that it was possible to
      obtain two coloured images, which highlights the potential this technique has for
      high-content screening, imaging of multiple epitopes and live cell imaging. 

PMID- 24130669
TI  - Endurance exercise diverts the balance between Th17 cells and regulatory T cells.
AB  - Endurance, marathon-type exertion is known to induce adverse changes in the
      immune system. Increased airway hyper-responsiveness and airway inflammation are
      well documented in endurance athletes and endurance exercise is considered a
      major risk factor for asthma in elite athletes. Yet, the mechanisms underlying
      this phenomenon are still to be deduced. We studied the effect of strenuous
      endurance exercise (marathon and half-ironman triathlon) on CD4+ lymphocyte sub
      populations and on the balance between effector and regulatory CD4+ lymphocytes
      in the peripheral blood of trained athletes, Endurance exercise induced a
      significant increase in Th17 cells and a sustained decrease in peripheral blood
      regulatory T cells (Tregs). While interleukin (IL)-2 levels remained
      undetectable, post-race serum IL-6 and transforming growth factor (TGF) beta
      levels were significantly elevated. Treg levels in sedentary controls' decreased
      in vitro after incubation with athletes' post-exercise serum, an effect that was
      attenuated by supplements of IL-2 or anti IL-6 neutralizing antibodies. Our data
      suggest that exercise-induced changes in serum cytokine levels promote
      alterations in Tregs and Th17 cell populations, which may divert the subtle
      balance in the immune system towards inflammation. This may explain allergic and
      autoimmune phenomena previously reported in endurance athletes and contribute to
      our understanding of exercise-related asthma. 

PMID- 24130671
TI  - Comparison of the laboratory standard washing using CIPAC washing agent and the
      domestic washing on three recommended types of long-lasting insecticidal mosquito
      nets.
AB  - BACKGROUND: One of the best ways to prevent malaria is the use of insecticide
      treated bed nets. Manufacturers pursue easier, safer and more efficient nets.
      Hence, many studies on the efficacy and wash resistance using World Health
      Organization standards have been reported. The commonly used detergent is "Savon
      de Marseille", because it closely resembles actually used soaps. At the 54(th)
      Collaborative International Pesticides Analytical Council (CIPAC) Technical
      Meeting in 2010, it was suggested to replace it by a standardized "CIPAC washing
      agent". The aim of this study was to investigate the difference between a
      laboratory hand washing simulation using the CIPAC washing agent (method-1) and a
      domestic washing (method-2) on different bed nets, as well as the effect of the
      drying process on the release of active ingredient. METHODS: Interceptor(r),
      Permanet(r)2.0 and Netprotect(r) nets were used in three treatments, each
      repeated 20 times. The first treatment included method-1 washing and indoor
      drying. The second treatment included method-2 washing and indoor drying. The
      third treatment used method-2 washing and UV-drying. The residual insecticide
      contents were determined using gas chromatography. RESULTS: The washing procedure
      and the number of washes have a significant effect on the release of active
      ingredient. Statistically, the two washing methods have the same effect on
      removing the active ingredient from the Interceptor(r) and Permanet(r)2.0 net,
      but a significantly different influence on the Netprotect(r) nets. The drying
      process has no significant effect on the insecticide. CONCLUSION: Both washing
      procedures affected the amount of insecticide remaining on nets independently of
      the impregnation technology. The active ingredient decreases with the number of
      washing cycles following an exponential or logarithmic model for coated nets. The
      laboratory hand washing simulation had more impact on the decrease of active
      ingredient content of the Netprotect(r) nets. All net types seemed to be
      effectively protected against UV-light.

PMID- 24130670
TI  - Genome analysis coupled with physiological studies reveals a diverse nitrogen
      metabolism in Methylocystis sp. strain SC2.
AB  - BACKGROUND: Methylocystis sp. strain SC2 can adapt to a wide range of methane
      concentrations. This is due to the presence of two isozymes of particulate
      methane monooxygenase exhibiting different methane oxidation kinetics. To gain
      insight into the underlying genetic information, its genome was sequenced and
      found to comprise a 3.77 Mb chromosome and two large plasmids. PRINCIPAL
      FINDINGS: We report important features of the strain SC2 genome. Its sequence is
      compared with those of seven other methanotroph genomes, comprising members of
      the Alphaproteobacteria, Gammaproteobacteria, and Verrucomicrobia. While the pan
      genome of all eight methanotroph genomes totals 19,358 CDS, only 154 CDS are
      shared. The number of core genes increased with phylogenetic relatedness: 328 CDS
      for proteobacterial methanotrophs and 1,853 CDS for the three
      alphaproteobacterial Methylocystaceae members, Methylocystis sp. strain SC2 and
      strain Rockwell, and Methylosinus trichosporium OB3b. The comparative study was
      coupled with physiological experiments to verify that strain SC2 has diverse
      nitrogen metabolism capabilities. In correspondence to a full complement of 34
      genes involved in N2 fixation, strain SC2 was found to grow with atmospheric N2
      as the sole nitrogen source, preferably at low oxygen concentrations.
      Denitrification-mediated accumulation of 0.7 nmol (30)N2/hr/mg dry weight of
      cells under anoxic conditions was detected by tracer analysis. N2 production is
      related to the activities of plasmid-borne nitric oxide and nitrous oxide
      reductases. CONCLUSIONS/PERSPECTIVES: Presence of a complete denitrification
      pathway in strain SC2, including the plasmid-encoded nosRZDFYX operon, is unique
      among known methanotrophs. However, the exact ecophysiological role of this
      pathway still needs to be elucidated. Detoxification of toxic nitrogen compounds
      and energy conservation under oxygen-limiting conditions are among the possible
      roles. Relevant features that may stimulate further research are, for example,
      absence of CRISPR/Cas systems in strain SC2, high number of iron acquisition
      systems in strain OB3b, and large number of transposases in strain Rockwell.

PMID- 24130672
TI  - Effect of prenatal alcohol exposure on childhood academic outcomes: contrasting
      maternal and paternal associations in the ALSPAC study.
AB  - BACKGROUND: The impact of low-to-moderate levels of alcohol consumption during
      pregnancy on child cognitive outcomes has been of recent concern. This study has
      tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is
      associated with lower school test scores at age 11 in the offspring via
      intrauterine mechanisms. METHODS: We used data from the Avon Longitudinal Study
      of Parents and Children (ALSPAC), a birth cohort study based in the South West of
      England. Analyses were conducted on 7062 participants who had complete data on:
      maternal and paternal patterns of alcohol use in the first trimester and at 18
      weeks' gestation, child's academic outcomes measured at age 11, gender, maternal
      age, parity, marital status, ethnicity, household crowding, home ownership status
      and parental education. We contrasted the association of mother's alcohol
      consumption during pregnancy with child's National Curriculum Key Stage 2 (KS2)
      test scores with the association for father's alcohol consumption (during the
      time the mother was pregnant) with child's National Curriculum Key Stage 2 (KS2)
      test scores. We used multivariate linear regression to estimate mean differences
      and 95% confidence intervals [CI] in KS2 scores across the exposure categories
      and computed f statistics to compare maternal and paternal associations. FINDINGS
      AND CONCLUSIONS: Drinking up to 1 unit of alcohol a day during pregnancy was not
      associated with lower test scores. However, frequent prenatal consumption of 4
      units (equivalent to 32 grams of alcohol) on each single drinking occasion was
      associated with reduced educational attainment [Mean change in offspring KS2
      score was -0.68 (-1.03, -0.33) for maternal alcohol categories compared to 0.27
      (0.07, 0.46) for paternal alcohol categories]. Frequent consumption of 4 units of
      alcohol during pregnancy may adversely affect childhood academic outcomes via
      intrauterine mechanisms.

PMID- 24130673
TI  - Effectiveness of a multimodal community intervention program to prevent suicide
      and suicide attempts: a quasi-experimental study.
AB  - BACKGROUND: Multilevel and multimodal interventions have been suggested for
      suicide prevention. However, few studies have reported the outcomes of such
      interventions for suicidal behaviours. METHODS: We examined the effectiveness of
      a community-based multimodal intervention for suicide prevention in rural areas
      with high suicide rates, compared with a parallel prevention-as-usual control
      group, covering a total of 631,133 persons. The effectiveness was also examined
      in highly populated areas near metropolitan cities (1,319,972 persons). The
      intervention started in July 2006, and continued for 3.5 years. The primary
      outcome was the incidence of composite outcome, consisting of completed suicides
      and suicide attempts requiring admission to an emergency ward for critical care.
      We compared the rate ratios (RRs) of the outcomes adjusted by sex, age group,
      region, period and interaction terms. Analyses were performed on an intention-to
      treat basis and stratified by sex and age groups. FINDINGS: In the rural areas,
      the overall median adherence of the intervention was significantly higher. The RR
      of the composite outcome in the intervention group decreased 7% compared with
      that of the control group. Subgroup analyses demonstrated heterogeneous effects
      among subpopulations: the RR of the composite outcome in the intervention group
      was significantly lower in males (RR = 0.77, 95% CI 0.59-0.998, p = 0.0485) and
      the RR of suicide attempts was significantly lower in males (RR = 0.39, 95% CI
      0.22-0.68, p = 0.001) and the elderly (RR = 0.35, 95% CI 0.17-0.71, p = 0.004).
      The intervention had no effect on the RR of the composite outcome in the highly
      populated areas. INTERPRETATION: Our findings suggest that this community-based
      multimodal intervention for suicide prevention could be implemented in rural
      areas, but not in highly populated areas. The effectiveness of the intervention
      was shown for males and for the elderly in rural areas. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00737165 UMIN Clinical Trials Registry UMIN000000460.

PMID- 24130674
TI  - The prevalence of and factors associated with the use of smoking cessation
      medication in Korea: trend between 2005-2011.
AB  - BACKGROUND: In Korea, nicotine replacement therapy (NRT) has been widely used in
      government-led, public health center-based smoking cessation services since 2004
      and varenicline has become available from 2007 but without reimbursement. In this
      study which used a series of nationwide cross-sectional surveys in Korea
      performed from 2005 to 2011, we examined the prevalence of smoking cessation
      medication use and factors associated with it. METHODS: We analyzed data from the
      third to fifth waves of Korean National Health and Nutrition Examination Survey
      (2005-2011). Prevalence of each smoking cessation method use was calculated for
      each year, and its secular trend was tested by multivariate logistic regression.
      RESULTS: Among smokers who made quit attempt during the previous year, 15.7% had
      used smoking cessation medications,15.3% had used NRT, and 0.7% had used
      prescription medication. There was a significant increasing trend for NRT use
      (P<0.001) during the study period, but use of prescription medication did not
      show any increase over time (P = 0.654) Education on smoking prevention and
      cessation was associated with smoking cessation medications use (OR 2.08, 95% CI
      1.58-2.75). CONCLUSIONS: While the use of NRT has increased over years through
      government-sponsored smoking cessation programs, use of prescription drugs
      remained very low and flat probably due to lack of reimbursement. Education of
      smokers about effective smoking cessation methods and change in reimbursement
      policy are suggested to stimulate evidence-based smoking cessation practice.

PMID- 24130675
TI  - Assessing species distribution using Google Street View: a pilot study with the
      Pine Processionary Moth.
AB  - Mapping species spatial distribution using spatial inference and prediction
      requires a lot of data. Occurrence data are generally not easily available from
      the literature and are very time-consuming to collect in the field. For that
      reason, we designed a survey to explore to which extent large-scale databases
      such as Google maps and Google Street View could be used to derive valid
      occurrence data. We worked with the Pine Processionary Moth (PPM) Thaumetopoea
      pityocampa because the larvae of that moth build silk nests that are easily
      visible. The presence of the species at one location can therefore be inferred
      from visual records derived from the panoramic views available from Google Street
      View. We designed a standardized procedure allowing evaluating the presence of
      the PPM on a sampling grid covering the landscape under study. The outputs were
      compared to field data. We investigated two landscapes using grids of different
      extent and mesh size. Data derived from Google Street View were highly similar to
      field data in the large-scale analysis based on a square grid with a mesh of 16
      km (96% of matching records). Using a 2 km mesh size led to a strong divergence
      between field and Google-derived data (46% of matching records). We conclude that
      Google database might provide useful occurrence data for mapping the distribution
      of species which presence can be visually evaluated such as the PPM. However, the
      accuracy of the output strongly depends on the spatial scales considered and on
      the sampling grid used. Other factors such as the coverage of Google Street View
      network with regards to sampling grid size and the spatial distribution of host
      trees with regards to road network may also be determinant.

PMID- 24130676
TI  - Experimental diabetes induces structural, inflammatory and vascular changes of
      Achilles tendons.
AB  - This study aims to demonstrate how the state of chronic hyperglycemia from
      experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons
      and, consequently, lead to the characteristics of tendinopathy. Twenty animals
      were randomly divided into two experimental groups: control group, consisting of
      healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus
      I. After twenty-four days of the induction of Diabetes type I, the Achilles
      tendon were removed for morphological evaluation, cellularity, number and cross
      sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF
      and NF-kappaB nuclear localization sequence (NLS) and nitrate and nitrite level.
      The Achilles tendon thickness (um/100g) of diabetic animals was significantly
      increased and, similarly, an increase was observed in the density of fibrocytes
      and mast cells in the tendons of the diabetic group. The average number of blood
      vessels per field, in peritendinous tissue, was statistically higher in the
      diabetic group 3.39 (2.98) vessels/field when compared to the control group 0.89
      (1.68) vessels/field p = 0.001 and in the intratendinous region, it was observed
      that blood vessels were extremely rare in the control group 0.035 (0.18)
      vessels/field and were often present in the tendons of the diabetic group 0.89
      (0.99) vessels/field. The immunohistochemistry analysis identified higher density
      of type 1 collagen and increased expression of VEGF as well as increased
      immunostaining for NFkappaB p50 NLS in the nucleus in Achilles tendon of the
      diabetic group when compared to the control group. Higher levels of
      nitrite/nitrate were observed in the experimental group induced to diabetes. We
      conclude that experimental DM induces notable structural, inflammatory and
      vascular changes in the Achilles tendon which are compatible with the process of
      chronic tendinopathy. 

PMID- 24130678
TI  - Metabolism of AGEs--bacterial AGEs are degraded by metallo-proteases.
AB  - Advanced Glycation End Products (AGEs) are the final products of non-enzymatic
      protein glycation that results in loss of protein structure and function. We have
      previously shown that in E. coli AGEs are continually formed as high-molecular
      weight protein complexes. Moreover, we showed that AGEs are removed from the
      cells by an active, ATP-dependent secretion and that these secreted molecules
      have low molecular weight. Taken together, these results indicate that E. coli
      contains a fraction of low molecular weight AGEs, in addition to the high
      molecular weight AGEs. Here we show that the low-molecular weight AGEs originate
      from high-molecular weight AGEs by proteolytic degradation. Results of in-vitro
      and in vivo experiments indicated that this degradation is carried out not by the
      major ATP-dependent proteases that are responsible for the main part of bacterial
      protein quality control but by an alternative metal-dependent proteolysis. This
      proteolytic reaction is essential for the further secretion of AGEs from the
      cells. As the biochemical reactions involving AGEs are not yet understood, the
      implication of a metalloprotease in breakdown of high molecular weight AGEs and
      their secretion constitutes an important step in the understanding of AGEs
      metabolism. 

PMID- 24130679
TI  - Quantifying assemblage turnover and species contributions at ecologic boundaries.
AB  - Not all boundaries, whether stratigraphical or geographical, are marked by
      species-level changes in community composition. For example, paleodata for some
      sites do not show readily discernible glacial-interglacial contrasts. Rather, the
      proportional abundances of species can vary subtly between glacials and
      interglacials. This paper presents a simple quantitative measure of assemblage
      turnover (assemblage turnover index, ATI) that uses changes in species'
      proportional abundances to identify intervals of community change. A second,
      functionally-related index (conditioned-on-boundary index, CoBI) identifies
      species contributions to the total assemblage turnover. With these measures we
      examine benthonic foraminiferal assemblages to assess glacial/interglacial
      contrasts at abyssal depths. Our results indicate that these measures, ATI and
      CoBI, have potential as sequence stratigraphic tools in abyssal depth deposits.
      Many peaks in the set of values of ATI coincide with terminations at the end of
      glaciations and delineate peak-bounded ATI intervals (PATIs) separated by
      boundaries that approximate to glacial terminations and to transgressions at
      neritic depths. These measures, however, can be used to evaluate the assemblage
      turnover and composition at any defined ecological or paleoecological boundary.
      The section used is from Ocean Drilling Program (OPD) Hole 994C, drilled on the
      Blake Ridge, offshore SE USA. 

PMID- 24130677
TI  - The housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT)
      regulates multiple developmental and metabolic pathways of murine embryonic stem
      cell neuronal differentiation.
AB  - The mechanisms by which mutations of the purinergic housekeeping gene
      hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the severe
      neurodevelopmental Lesch Nyhan Disease (LND) are poorly understood. The best
      recognized neural consequences of HPRT deficiency are defective basal ganglia
      expression of the neurotransmitter dopamine (DA) and aberrant DA neuronal
      function. We have reported that HPRT deficiency leads to dysregulated expression
      of multiple DA-related developmental functions and cellular signaling defects in
      a variety of HPRT-deficient cells, including human induced pluripotent stem (iPS)
      cells. We now describe results of gene expression studies during neuronal
      differentiation of HPRT-deficient murine ESD3 embryonic stem cells and report
      that HPRT knockdown causes a marked switch from neuronal to glial gene expression
      and dysregulates expression of Sox2 and its regulator, genes vital for stem cell
      pluripotency and for the neuronal/glial cell fate decision. In addition, HPRT
      deficiency dysregulates many cellular functions controlling cell cycle and
      proliferation mechanisms, RNA metabolism, DNA replication and repair, replication
      stress, lysosome function, membrane trafficking, signaling pathway for platelet
      activation (SPPA) multiple neurotransmission systems and sphingolipid, sulfur and
      glycan metabolism. We propose that the neural aberrations of HPRT deficiency
      result from combinatorial effects of these multi-system metabolic errors. Since
      some of these aberrations are also found in forms of Alzheimer's and Huntington's
      disease, we predict that some of these systems defects play similar
      neuropathogenic roles in diverse neurodevelopmental and neurodegenerative
      diseases in common and may therefore provide new experimental opportunities for
      clarifying pathogenesis and for devising new potential therapeutic targets in
      developmental and genetic disease. 

PMID- 24130680
TI  - Cognitive modulation of psychophysical, respiratory and autonomic responses to
      cold pressor test.
AB  - In healthy subjects with high hypnotisability (highs) under hypnosis,
      subjectively effective suggestions for analgesia abolish the increases in blood
      pressure associated with cold pressor test (cpt) by reducing the peripheral
      vascular resistance. The aim of the present study was to investigate the effects
      of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22)
      and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was
      administered without (CPT) and with suggestions for analgesia (CPT+AN).
      Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion)
      and pain tolerance, defined as the difference between cpt duration and pain
      threshold), respiratory (amplitude and frequency) and autonomic variables (tonic
      skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin
      blood flow) were studied. The suggestions for analgesia increased cpt duration
      and RR in both groups, but decreased pain intensity and enhanced pain threshold
      only in highs; in both groups they did not modulate systolic blood pressure,
      tonic skin conductance and skin blood flow; thus, increased parasympathetic
      activity appears responsible for the heart rate reduction induced by suggestions
      in both groups. In conclusion, our findings show that suggestions modulate pain
      experience differentially in highs and lows, and are partially effective also in
      lows. We hypothesize that the mechanisms responsible for the efficacy of
      suggestions in healthy lows may be involved also in their efficacy in chronic
      pain patients with low hypnotisability. 

PMID- 24130682
TI  - Genetic structure of Tibeto-Burman populations of Bangladesh: evaluating the gene
      flow along the sides of Bay-of-Bengal.
AB  - Human settlement and migrations along sides of Bay-of-Bengal have played a vital
      role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast
      Asia. Bangladesh and Northeast India form the vital land bridge between the South
      and Southeast Asia. To reconstruct the population history of this region and to
      see whether this diverse region geographically acted as a corridor or barrier for
      human interaction between South Asia and Southeast Asia, we, for the first time
      analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental
      autosomal genetic markers among aboriginal Bangladesh tribes currently speaking
      Tibeto-Burman language. All the three studied populations; Chakma, Marma and
      Tripura from Bangladesh showed strikingly high homogeneity among themselves and
      strong affinities to Northeast Indian Tibeto-Burman groups. However, they show
      substantially higher molecular diversity than Northeast Indian populations.
      Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both
      males and females in shaping the Tibeto-Burman expansion in Southern Asia.
      Moreover, it is noteworthy that in admixture proportion, TB populations of
      Bangladesh carry substantially higher mainland Indian ancestry component than
      Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major
      paternal haplogroups (O2a and O3a3c), suggested that they arose before the
      differentiation of any language group and approximately at the same time.
      Contrary to the scenario proposed for colonization of Northeast India as male
      founder effect that occurred within the past 4,000 years, we suggest a
      significantly deep colonization of this region. Overall, our extensive analysis
      revealed that the population history of South Asian Tibeto-Burman speakers is
      more complex than it was suggested before. 

PMID- 24130681
TI  - A key role of microRNA-29b for the suppression of colon cancer cell migration by
      American ginseng.
AB  - Metastasis of colon cancer cells increases the risk of colon cancer mortality. We
      have recently shown that American ginseng prevents colon cancer, and a Hexane
      extract of American Ginseng (HAG) has particularly potent anti-inflammatory and
      anti-cancer properties. Dysregulated microRNA (miR) expression has been observed
      in several disease conditions including colon cancer. Using global miR expression
      profiling, we observed increased miR-29b in colon cancer cells following exposure
      to HAG. Since miR-29b plays a role in regulating the migration of cancer cells,
      we hypothesized that HAG induces miR-29b expression to target matrix
      metalloproteinase-2 (MMP-2) thereby suppressing the migration of colon cancer
      cells. Results are consistent with this hypothesis. Our study supports the
      understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG
      suppresses the migration of colon cancer cells. 

PMID- 24130683
TI  - Munc13-like skMLCK variants cannot mimic the unique calmodulin binding mode of
      Munc13 as evidenced by chemical cross-linking and mass spectrometry.
AB  - Among the neuronal binding partners of calmodulin (CaM) are Munc13 proteins as
      essential presynaptic regulators that play a key role in synaptic vesicle priming
      and are crucial for presynaptic short-term plasticity. Recent NMR structural
      investigations of a CaM/Munc13-1 peptide complex have revealed an extended
      structure, which contrasts the compact structures of most classical CaM/target
      complexes. This unusual binding mode is thought to be related to the presence of
      an additional hydrophobic anchor residue at position 26 of the CaM binding motif
      of Munc13-1, resulting in a novel 1-5-8-26 motif. Here, we addressed the question
      whether the 1-5-8-26 CaM binding motif is a Munc13-related feature or whether it
      can be induced in other CaM targets by altering the motif's core residues. For
      this purpose, we chose skeletal muscle myosin light chain kinase (skMLCK) with a
      classical 1-5-8-14 CaM binding motif and constructed three skMLCK peptide
      variants mimicking Munc13-1, in which the hydrophobic anchor amino acid at
      position 14 was moved to position 26. Chemical cross-linking between CaM and
      skMLCK peptide variants combined with high-resolution mass spectrometry yielded
      insights into the peptides' binding modes. This structural comparison together
      with complementary binding data from surface plasmon resonance experiments
      revealed that skMLCK variants with an artificial 1-5-8-26 motif cannot mimic CaM
      binding of Munc13-1. Apparently, additional features apart from the spacing of
      the hydrophobic anchor residues are required to define the functional 1-5-8-26
      motif of Munc13-1. We conclude that Munc13 proteins display a unique CaM binding
      behavior to fulfill their role as efficient presynaptic calcium sensors over
      broad range of Ca(2+) concentrations. 

PMID- 24130684
TI  - Testing the PRISMA-Equity 2012 reporting guideline: the perspectives of
      systematic review authors.
AB  - Reporting guidelines can be used to encourage standardised and comprehensive
      reporting of health research. In light of the global commitment to health equity,
      we have previously developed and published a reporting guideline for equity
      focused systematic reviews (PRISMA-E 2012). The objectives of this study were to
      explore the utility of the equity extension items included in PRISMA-E 2012 from
      a systematic review author perspective, including facilitators and barriers to
      its use. This will assist in designing dissemination and knowledge translation
      strategies. We conducted a survey of systematic review authors to expose them to
      the new items in PRISMA-E 2012, establish the extent to which they had
      historically addressed those items in their own reviews, and gather feedback on
      the usefulness of the new items. Data were analysed using Microsoft Excel 2008
      and Stata (version 11.2 for Mac). Of 151 respondents completing the survey, 18.5%
      (95% CI: 12.7% to 25.7%) had not heard of the PRISMA statement before, although
      83.4% (95% CI: 77.5% to 89.3%) indicated that they plan to use PRISMA-E 2012 in
      the future, depending on the focus of their review. Most (68.9%; 95% CI: 60.8% to
      76.2%) thought that using PRISMA-E 2012 would lead them to conduct their reviews
      differently. Important facilitators to using PRISMA-E 2012 identified by
      respondents were journal endorsement and incorporation of the elements of the
      guideline into systematic review software. Barriers identified were lack of time,
      word limits and the availability of equity data in primary research. This study
      has been the first to 'road-test' the new PRISMA-E 2012 reporting guideline and
      the findings are encouraging. They confirm the acceptability and potential
      utility of the guideline to assist review authors in reporting on equity in their
      reviews. The uptake and impact of PRISMA-E 2012 over time on design, conduct and
      reporting of primary research and systematic reviews should continue to be
      examined. 

PMID- 24130685
TI  - High-throughput screening (HTS) and hit validation to identify small molecule
      inhibitors with activity against NS3/4A proteases from multiple hepatitis C virus
      genotypes.
AB  - Development of drug-resistant mutations has been a major problem with all
      currently developed Hepatitis C Virus (HCV) NS3/4A inhibitors, including the two
      FDA approved drugs, significantly reducing the efficacy of these inhibitors. The
      high incidence of drug-resistance mutations and the limited utility of these
      inhibitors against only genotype 1 highlight the need for novel, broad-spectrum
      HCV therapies. Here we used high-throughput screening (HTS) to identify low
      molecular weight inhibitors against NS3/4A from multiple genotypes. A total of
      40,967 compounds from four structurally diverse molecular libraries were screened
      by HTS using fluorescence-based enzymatic assays, followed by an orthogonal
      binding analysis using surface plasmon resonance (SPR) to eliminate false
      positives. A novel small molecule compound was identified with an IC50 value of
      2.2 uM against the NS3/4A from genotype 1b. Mode of inhibition analysis
      subsequently confirmed this compound to be a competitive inhibitor with respect
      to the substrate, indicating direct binding to the protease active site, rather
      than to the allosteric binding pocket that was discovered to be the binding site
      of a few recently discovered small molecule inhibitors. This newly discovered
      inhibitor also showed promising inhibitory activity against the NS3/4As from
      three other HCV genotypes, as well as five common drug-resistant mutants of
      genotype 1b NS3/4A. The inhibitor was selective for NS3 from multiple HCV
      genotypes over two human serine proteases, and a whole cell lysate assay
      confirmed inhibitory activity in the cellular environment. This compound provides
      a lead for further development of potentially broader spectrum inhibitors. 

PMID- 24130686
TI  - Hierarchical, multi-sensor based classification of daily life activities:
      comparison with state-of-the-art algorithms using a benchmark dataset.
AB  - Insufficient physical activity is the 4th leading risk factor for mortality.
      Methods for assessing the individual daily life activity (DLA) are of major
      interest in order to monitor the current health status and to provide feedback
      about the individual quality of life. The conventional assessment of DLAs with
      self-reports induces problems like reliability, validity, and sensitivity. The
      assessment of DLAs with small and light-weight wearable sensors (e.g. inertial
      measurement units) provides a reliable and objective method. State-of-the-art
      human physical activity classification systems differ in e.g. the number and kind
      of sensors, the performed activities, and the sampling rate. Hence, it is
      difficult to compare newly proposed classification algorithms to existing
      approaches in literature and no commonly used dataset exists. We generated a
      publicly available benchmark dataset for the classification of DLAs. Inertial
      data were recorded with four sensor nodes, each consisting of a triaxial
      accelerometer and a triaxial gyroscope, placed on wrist, hip, chest, and ankle.
      Further, we developed a novel, hierarchical, multi-sensor based classification
      system for the distinction of a large set of DLAs. Our hierarchical
      classification system reached an overall mean classification rate of 89.6% and
      was diligently compared to existing state-of-the-art algorithms using our
      benchmark dataset. For future research, the dataset can be used in the evaluation
      process of new classification algorithms and could speed up the process of
      getting the best performing and most appropriate DLA classification system. 

PMID- 24130687
TI  - Low vitamin D status is associated with nonalcoholic Fatty liver disease
      independent of visceral obesity in Korean adults.
AB  - OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D
      [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of
      visceral obesity in Koreans and to examine whether the associations differ
      according to the presence of diabetes or insulin resistance. RESEARCH DESIGN AND
      METHODS: A total of 1081 adults were enrolled from a population-based cohort in
      Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin
      resistance was measured by homeostasis model assessment of insulin resistance
      (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver
      attenuation index (LAI, the difference between the mean hepatic and splenic
      attenuation) was <5 Hounsfield Units. RESULTS: In subjects with diabetes (n =
      282), 25(OH)D levels were negatively associated with waist circumference, fasting
      insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were
      positively associated with LAI after adjusting for age, sex, season, exercise,
      and vitamin supplementation. In subjects without diabetes, only triglyceride
      level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for
      NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects
      with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5
      (95% CI:1.0-6.2)]. In contrast, no significant difference in OR was observed in
      subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR,
      an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was
      observed in the high HOMA-IR (>=2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4
      10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3-1.9)].
      CONCLUSIONS: Low vitamin D status is closely associated with NAFLD, independent
      of visceral obesity in subjects with diabetes or insulin resistance.

PMID- 24130689
TI  - A quantitative method for assessment of prescribing patterns using electronic
      health records.
AB  - BACKGROUND: Most available quality indicators for hospitals are represented by
      simple ratios or proportions, and are limited to specific events. A generalized
      method that can be applied to diverse clinical events has not been developed. The
      aim of this study was to develop a simple method of evaluating physicians'
      prescription patterns for diverse events and their level of awareness of clinical
      practice guidelines. METHODS AND FINDINGS: We developed a quantitative method
      called Prescription pattern Around Clinical Event (PACE), which is applicable to
      electronic health records (EHRs). Three discrete prescription patterns
      (intervention, maintenance, and discontinuation) were determined based on the
      prescription change index (PCI), which was calculated by means of the increase or
      decrease in the prescription rate after a clinical event. Hyperkalemia and
      Clostridium difficile-associated diarrhea (CDAD) were used as example cases. We
      calculated the PCIs of 10 drugs related to hyperkalemia, categorized them into
      prescription patterns, and then compared the resulting prescription patterns with
      the known standards for hyperkalemia treatment. The hyperkalemia knowledge of
      physicians was estimated using a questionnaire and compared to the prescription
      pattern. Prescriptions for CDAD were also determined and compared to clinical
      knowledge. Clinical data of 1698, 348, and 1288 patients were collected from EHR
      data. The physicians prescribing behaviors for hyperkalemia and CDAD were
      concordant with the standard knowledge. Prescription patterns were well
      correlated with individual physicians' knowledge of hyperkalemia (kappa = 0.714).
      Prescribing behaviors according to event severity or clinical condition were
      plotted as a simple summary graph. CONCLUSION: The algorithm successfully
      assessed the prescribing patterns from the EHR data. The prescription patterns
      were well correlated with physicians' knowledge. We expect that this algorithm
      will enable quantification of prescribers' adherence to clinical guidelines and
      be used to facilitate improved prescribing practices.

PMID- 24130688
TI  - IVIg immune reconstitution treatment alleviates the state of persistent immune
      activation and suppressed CD4 T cell counts in CVID.
AB  - Common variable immunodeficiency (CVID) is characterized by defective B cell
      function, impaired antibody production, and increased susceptibility to bacterial
      infections. Here, we addressed the hypothesis that poor antibody-mediated immune
      control of infections may result in substantial perturbations in the T cell
      compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months
      after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naive
      CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell
      (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T
      cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory
      receptors CD80 and CD83 was elevated in mDCs and correlated with T cell
      activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were
      low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was
      elevated. Importantly, immune reconstitution treatment with IVIg partially
      restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the
      levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells
      and iNKT cells remained low. Thus, primary deficiency in humoral immunity with
      impaired control of microbial infections is associated with significant
      pathological changes in cell-mediated immunity. Furthermore, therapeutic
      enhancement of humoral immunity with IVIg infusions alleviates several of these
      defects, indicating a relationship between poor antibody-mediated immune control
      of infections and the occurrence of abnormalities in the T cell and mDC
      compartments. These findings help our understanding of the immunopathogenesis of
      primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1
      infection. 

PMID- 24130690
TI  - What lies beneath: sub-articular long bone shape scaling in eutherian mammals and
      saurischian dinosaurs suggests different locomotor adaptations for gigantism.
AB  - Eutherian mammals and saurischian dinosaurs both evolved lineages of huge
      terrestrial herbivores. Although significantly more saurischian dinosaurs were
      giants than eutherians, the long bones of both taxa scale similarly and suggest
      that locomotion was dynamically similar. However, articular cartilage is thin in
      eutherian mammals but thick in saurischian dinosaurs, differences that could have
      contributed to, or limited, how frequently gigantism evolved. Therefore, we
      tested the hypothesis that sub-articular bone, which supports the articular
      cartilage, changes shape in different ways between terrestrial mammals and
      dinosaurs with increasing size. Our sample consisted of giant mammal and reptile
      taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with
      thin and thick articular cartilage. Our results show that eutherian mammal sub
      articular shape becomes narrow with well-defined surface features as size
      increases. In contrast, this region in saurischian dinosaurs expands and remains
      gently convex with increasing size. Similar trends were observed in non-erect
      outgroup taxa (monotremes, alligators), showing that the trends we report are
      posture-independent. These differences support our hypothesis that sub-articular
      shape scales differently between eutherian mammals and saurischian dinosaurs. Our
      results show that articular cartilage thickness and sub-articular shape are
      correlated. In mammals, joints become ever more congruent and thinner with
      increasing size, whereas archosaur joints remained both congruent and thick,
      especially in sauropods. We suggest that gigantism occurs less frequently in
      mammals, in part, because joints composed of thin articular cartilage can only
      become so congruent before stress cannot be effectively alleviated. In contrast,
      frequent gigantism in saurischian dinosaurs may be explained, in part, by joints
      with thick articular cartilage that can deform across large areas with increasing
      load. 

PMID- 24130691
TI  - Prairie dog decline reduces the supply of ecosystem services and leads to
      desertification of semiarid grasslands.
AB  - Anthropogenic impacts on North American grasslands, a highly endangered
      ecosystem, have led to declines of prairie dogs, a keystone species, over 98% of
      their historical range. While impacts of this loss on maintenance of grassland
      biodiversity have been widely documented, much less is known about the
      consequences on the supply of ecosystem services. Here we assessed the effect of
      prairie dogs in the supply of five ecosystem services by comparing grasslands
      currently occupied by prairie dogs, grasslands devoid of prairie dogs, and areas
      that used to be occupied by prairie dogs that are currently dominated by mesquite
      scrub. Groundwater recharge, regulation of soil erosion, regulation of soil
      productive potential, soil carbon storage and forage availability were
      consistently quantitatively or qualitatively higher in prairie dog grasslands
      relative to grasslands or mesquite scrub. Our findings indicate a severe loss of
      ecosystem services associated to the absence of prairie dogs. These findings
      suggest that contrary to a much publicize perception, especially in the US,
      prairie dogs are fundamental in maintaining grasslands and their decline have
      strong negative impacts in human well - being through the loss of ecosystem
      services. 

PMID- 24130692
TI  - Entrapment of ciliates at the water-air interface.
AB  - The importance of water-air interfaces (WAI) on microorganism activities has been
      recognized by many researchers. In this paper, we report a novel phenomenon: the
      entrapment of ciliates Tetrahymena at the WAI. We first characterized the
      behavior of cells at the interface and showed that the cells' swimming velocity
      was considerably reduced at the WAI. To verify the possible causes of the
      entrapment, we investigated the effects of positive chemotaxis for oxygen,
      negative geotaxis and surface properties. Even though the taxes were still
      effective, the entrapment phenomenon was not dependent on the physiological
      conditions, but was instead affected by the physical properties at the interface.
      This knowledge is useful for a better understanding of the physiology of
      microorganisms at interfaces in nature and in industry. 

PMID- 24130693
TI  - ERP modulation during observation of abstract paintings by Franz Kline.
AB  - The aim of this study was to test the involvement of sensorimotor cortical
      circuits during the beholding of the static consequences of hand gestures devoid
      of any meaning.In order to verify this hypothesis we performed an EEG experiment
      presenting to participants images of abstract works of art with marked traces of
      brushstrokes. The EEG data were analyzed by using Event Related Potentials
      (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical
      circuits during the beholding of these selected works of abstract art. The
      stimuli consisted of three different abstract black and white paintings by Franz
      Kline. Results verified our experimental hypothesis showing the activation of
      premotor and motor cortical areas during stimuli observation. In addition,
      abstract works of art observation elicited the activation of reward-related
      orbitofrontal areas, and cognitive categorization-related prefrontal areas. The
      cortical sensorimotor activation is a fundamental neurophysiological
      demonstration of the direct involvement of the cortical motor system in
      perception of static meaningless images belonging to abstract art. These results
      support the role of embodied simulation of artist's gestures in the perception of
      works of art. 

PMID- 24130694
TI  - Thorough investigation of a canine autoinflammatory disease (AID) confirms one
      main risk locus and suggests a modifier locus for amyloidosis.
AB  - Autoinflammatory disease (AID) manifests from the dysregulation of the innate
      immune system and is characterised by systemic and persistent inflammation.
      Clinical heterogeneity leads to patients presenting with one or a spectrum of
      phenotypic signs, leading to difficult diagnoses in the absence of a clear
      genetic cause. We used separate genome-wide SNP analyses to investigate five
      signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis,
      otitis and systemic reactive amyloidosis) in a canine comparative model, the pure
      bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on
      chromosome 13 spanning two peaks of association. A three-marker haplotype based
      on the most significant SNP (p<2.6*10(-8)) from each analysis showed that one
      haplotypic pair (H13-11) was present in the majority of AID individuals,
      implicating this as a shared risk factor for all phenotypes. We also noted that a
      genetic signature (F ST) distinguishing the phenotypic extremes of the breed
      specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID
      locus; suggesting that breed development and differentiation has played a
      parallel role in the genetics of breed fitness. Intriguingly, a potential
      modifier locus for amyloidosis was revealed on chromosome 14, and an
      investigation of candidate genes from both this and the chromosome 13 regions
      revealed significant (p<0.05) renal differential expression in four genes
      previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6).
      These results illustrate that phenotypic heterogeneity need not be a reflection
      of genetic heterogeneity, and that genetic modifiers of disease could be masked
      if syndromes were not first considered as individual clinical signs and then as a
      sum of their component parts. 

PMID- 24130695
TI  - Inhibiting interleukin-19 activity ameliorates esophageal squamous cell carcinoma
      progression.
AB  - BACKGROUND: IL-19 is expressed in esophageal squamous cell carcinoma (SCC), but
      its biological effect on esophageal cancer remains unclear. We determined the
      correlation between IL-19 expression levels and clinicopathological variables and
      explored the effects of IL-19 on the esophageal SCC in vivo and in vitro.
      METHODOLOGY/PRINCIPAL FINDINGS: We determined the expression levels of esophageal
      SCC tissues from 60 patients using immunohistochemistry. We examined the effects
      of IL-19 on intracellular signaling, cytokines production as well as
      proliferation, colonization, and migration in the human esophageal SCC cell line
      CE81T. Monoclonal antibodies (mAbs) against IL-19 (1BB1) and its receptor IL-20R1
      (51D) were used to antagonize the effects of IL-19. We injected SCID mice with
      CE81T cells and then treated them with anti-IL-19 mAb or control IgG every 3 days
      and determined tumor growth for 32 days. Of the 60 esophageal SCC patients, 36
      patients (60%) were IL-19 strongly stained, which was associated with advanced
      tumor stage. CE81T cells expressed IL-19 and its receptors. IL-19 induced
      phosphorylation of STAT3, P38, JNK, ERK1/2, Akt, and NF-kappaB in CE81T cells. IL
      19 promoted the proliferation, colonization, and migration of CE81T cells, which
      were antagonized by 1BB1 and 51D. IL-19 also induced expression of the
      transcripts of TGF-beta, cyclin B1, CXCR4, and MMP-1 in CE81T cells. In CE81T
      tumor-bearing mice, 1BB1 reduced tumor growth and downregulated TGF-beta, cyclin
      B1, MMP-1, and CXCR4 expression in tumors. CONCLUSIONS/SIGNIFICANCE: IL-19
      affects the pathogenesis of esophageal cancer. IL-19 mAb (1BB1) is potentially a
      potent drug for esophageal cancer therapy.

PMID- 24130696
TI  - Systematic review and meta-analysis of validation studies on a diabetes case
      definition from health administrative records.
AB  - OBJECTIVES: Health administrative data are frequently used for diabetes
      surveillance. We aimed to determine the sensitivity and specificity of a commonly
      used diabetes case definition (two physician claims or one hospital discharge
      abstract record within a two-year period) and their potential effect on
      prevalence estimation. METHODS: Following Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched Medline
      (from 1950) and Embase (from 1980) databases for validation studies through
      August 2012 (keywords: "diabetes mellitus"; "administrative databases";
      "validation studies"). Reviewers abstracted data with standardized forms and
      assessed quality using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)
      criteria. A generalized linear model approach to random-effects bivariate
      regression meta-analysis was used to pool sensitivity and specificity estimates.
      We applied correction factors derived from pooled sensitivity and specificity
      estimates to prevalence estimates from national surveillance reports and
      projected prevalence estimates over 10 years (to 2018). RESULTS: The search
      strategy identified 1423 abstracts among which 11 studies were deemed relevant
      and reviewed; 6 of these reported sensitivity and specificity allowing pooling in
      a meta-analysis. Compared to surveys or medical records, sensitivity was 82.3%
      (95%CI 75.8, 87.4) and specificity was 97.9% (95%CI 96.5, 98.8). The diabetes
      case definition underestimated prevalence when it was <=10.6% and overestimated
      prevalence otherwise. CONCLUSION: The diabetes case definition examined misses up
      to one fifth of diabetes cases and wrongly identifies diabetes in approximately
      2% of the population. This may be sufficiently sensitive and specific for
      surveillance purposes, in particular monitoring prevalence trends. Applying
      correction factors to adjust prevalence estimates from this definition may be
      helpful to increase accuracy of estimates.

PMID- 24130697
TI  - Dynamic CT perfusion imaging of the myocardium: a technical note on improvement
      of image quality.
AB  - OBJECTIVE: To improve image and diagnostic quality in dynamic CT myocardial
      perfusion imaging (MPI) by using motion compensation and a spatio-temporal
      filter. METHODS: Dynamic CT MPI was performed using a 256-slice multidetector
      computed tomography scanner (MDCT). Data from two different patients-with and
      without myocardial perfusion defects-were evaluated to illustrate potential
      improvements for MPI (institutional review board approved). Three datasets for
      each patient were generated: (i) original data (ii) motion compensated data and
      (iii) motion compensated data with spatio-temporal filtering performed. In
      addition to the visual assessment of the tomographic slices, noise and contrast
      to-noise-ratio (CNR) were measured for all data. Perfusion analysis was performed
      using time-density curves with regions-of-interest (ROI) placed in normal and
      hypoperfused myocardium. Precision in definition of normal and hypoperfused areas
      was determined in corresponding coloured perfusion maps. RESULTS: The use of
      motion compensation followed by spatio-temporal filtering resulted in better
      alignment of the cardiac volumes over time leading to a more consistent perfusion
      quantification and improved detection of the extend of perfusion defects.
      Additionally image noise was reduced by 78.5%, with CNR improvements by a factor
      of 4.7. The average effective radiation dose estimate was 7.1+/-1.1 mSv.
      CONCLUSION: The use of motion compensation and spatio-temporal smoothing will
      result in improved quantification of dynamic CT MPI using a latest generation CT
      scanner.

PMID- 24130698
TI  - Large-scale collection and analysis of full-length cDNAs from Brachypodium
      distachyon and integration with Pooideae sequence resources.
AB  - A comprehensive collection of full-length cDNAs is essential for correct
      structural gene annotation and functional analyses of genes. We constructed a
      mixed full-length cDNA library from 21 different tissues of Brachypodium
      distachyon Bd21, and obtained 78,163 high quality expressed sequence tags (ESTs)
      from both ends of ca. 40,000 clones (including 16,079 contigs). We updated gene
      structure annotations of Brachypodium genes based on full-length cDNA sequences
      in comparison with the latest publicly available annotations. About 10,000 non
      redundant gene models were supported by full-length cDNAs; ca. 6,000 showed some
      transcription unit modifications. We also found ca. 580 novel gene models,
      including 362 newly identified in Bd21. Using the updated transcription start
      sites, we searched a total of 580 plant cis-motifs in the -3 kb promoter regions
      and determined a genome-wide Brachypodium promoter architecture. Furthermore, we
      integrated the Brachypodium full-length cDNAs and updated gene structures with
      available sequence resources in wheat and barley in a web-accessible database,
      the RIKEN Brachypodium FL cDNA database. The database represents a "one-stop"
      information resource for all genomic information in the Pooideae, facilitating
      functional analysis of genes in this model grass plant and seamless knowledge
      transfer to the Triticeae crops. 

PMID- 24130699
TI  - Egg-laying "intermorphs" in the ant Crematogaster smithi neither affect sexual
      production nor male parentage.
AB  - We study male parentage and between-colony variation in sex allocation and sexual
      production in the desert ant Crematogaster smithi, which usually has only one
      singly-mated queen per nest. Colonies of this species are known to temporarily
      store nutrients in the large fat body of intermorphs, a specialized female caste
      intermediate in morphology between queens and workers. Intermorphs repackage at
      least part of this fat into consumable but viable male-destined eggs. If these
      eggs sometimes develop instead of being eaten, intermorphs will be reproductive
      competitors of the queen but--due to relatedness asymmetries--allies of their
      sister worker. Using genetic markers we found a considerable proportion of non
      queen sons in some, but not all, colonies. Even though intermorphs produce ~1.7*
      more eggs than workers, their share in the parentage of adult males is estimated
      to be negligible due to their small number compared to workers. Furthermore,
      neither colony-level sex allocation nor overall sexual production was correlated
      with intermorph occurrence or number. We conclude that intermorph-laid eggs
      typically do not survive and that the storage of nutrients and their
      redistribution as eggs by intermorphs is effectively altruistic.

PMID- 24130700
TI  - Association between usual sodium and potassium intake and blood pressure and
      hypertension among U.S. adults: NHANES 2005-2010.
AB  - OBJECTIVES: Studies indicate high sodium and low potassium intake can increase
      blood pressure suggesting the ratio of sodium-to-potassium may be informative.
      Yet, limited studies examine the association of the sodium-to-potassium ratio
      with blood pressure and hypertension. METHODS: We analyzed data on 10,563
      participants aged >=20 years in the 2005-2010 National Health and Nutrition
      Examination Survey who were neither taking anti-hypertensive medication nor on a
      low sodium diet. We used measurement error models to estimate usual intakes,
      multivariable linear regression to assess their associations with blood pressure,
      and logistic regression to assess their associations with hypertension. RESULTS:
      The average usual intakes of sodium, potassium and sodium-to-potassium ratio were
      3,569 mg/d, 2,745 mg/d, and 1.41, respectively. All three measures were
      significantly associated with systolic blood pressure, with an increase of 1.04
      mmHg (95% CI, 0.27-1.82) and a decrease of 1.24 mmHg (95% CI, 0.31-2.70) per
      1,000 mg/d increase in sodium or potassium intake, respectively, and an increase
      of 1.05 mmHg (95% CI, 0.12-1.98) per 0.5 unit increase in sodium-to-potassium
      ratio. The adjusted odds ratios for hypertension were 1.40 (95% CI, 1.07-1.83),
      0.72 (95% CI, 0.53-0.97) and 1.30 (95% CI, 1.05-1.61), respectively, comparing
      the highest and lowest quartiles of usual intake of sodium, potassium or sodium
      to-potassium ratio. CONCLUSIONS: Our results provide population-based evidence
      that concurrent higher sodium and lower potassium consumption are associated with
      hypertension.

PMID- 24130701
TI  - Snapin, positive regulator of stimulation- induced Ca2+ release through RyR, is
      necessary for HIV-1 replication in T cells.
AB  - To identify critical host factors necessary for human immunodeficiency virus 1
      (HIV-1) replication, large libraries of short-peptide-aptamers were expressed
      retrovirally. The target of one inhibitor peptide, Pep80, identified in this
      screen was determined to be Snapin, a protein associated with the soluble N-ethyl
      maleimide sensitive factor adaptor protein receptor (SNARE) complex that is
      critical for calcium-dependent exocytosis during neurotransmission. Pep80
      inhibited Ca2+ release from intracellular stores and blocked downstream signaling
      by direct interruption of the association between Snapin and an intracellular
      calcium release channel, the ryanodine receptor (RyR). NFAT signaling was
      preferentially abolished by Pep80. Expression of Snapin overcame Pep80-mediated
      inhibition of Ca2+/NFAT signaling and HIV-1 replication. Furthermore, Snapin
      induced HIV-1 replication in primary CD4+ T cells. Thus, through its interaction
      with RyR, Snapin is a critical regulator of Ca2+ signaling and T cell activation.
      Use of the genetically selected intracellular aptamer inhibitors allowed us to
      define unique mechanisms important to HIV-1 replication and T cell biology.

PMID- 24130702
TI  - Atorvastatin decreases bone loss, inflammation and oxidative stress in
      experimental periodontitis.
AB  - The aim of this study is to determine the effects of Atorvastatin treatment, an
      inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, in
      periodontal disease. Male Wistar albino rats were randomly divided into five
      groups of ten rats each: (1) non-ligated treatment (NL), (2) ligature only (L),
      (3) ligature plus 1 mg/kg Atorvastatin daily for 10 days, (4) ligature plus 5
      mg/kg Atorvastatin daily for 10 days, and (5) ligature plus 10 mg/kg Atorvastatin
      daily for 10 days. Following the treatment course, the periodontal tissue of the
      animals was analyzed by Measurement of alveolar bone loss, Histopathology and
      immunohistochemistry to determine of the expression of COX-2, MMP-2, MMP9, and
      RANKL/RANK/OPG. ELISA assay was used to quantitate the levels of IL-1beta, IL-10,
      TNF-alpha, myeloperoxidase, malondialdehyde, and glutathione. The periodontal
      group treated with 10 mg/kg of Atorvastatin (3.9+/-0.9 mm; p<0.05) showed reverse
      the alveolar bone loss caused Experimental Periodontal Disease compared to (L)
      (7.02+/-0.17 mm). The periodontal group treated with 10 mg/kg of Atorvastatin
      showed a significant reduction in MPO and MDA (p<0.05) compared to ligature only
      group (L). Similarly in this group, the levels of the proinflammatory cytokines
      IL-1beta and TNF-alpha were significantly decreased (p<0.05). Furthermore, MMP-2,
      MMP-9, RANKL/RANK, and COX-2 were all downregulated by Atorvastatin treatment,
      while OPG expression was increased. The findings support a role of Atorvastatin
      for reducing the bone loss, inflammatory response, oxidative stress, and
      expression of extracellular matrix proteins, while reducing RANK/RANKL and
      increase OPG in periodontal disease. 

PMID- 24130703
TI  - Sleep-dependent consolidation of value-based learning.
AB  - It has been suggested that sleep selectively enhances memories with future
      relevance. Given that sleep's benefits can vary by item within a learning
      context, the present study investigated whether the amount of sleep-dependent
      consolidation may vary across items based on the value of the to-be-learned
      material. For this purpose, we used a value-based learning paradigm in which
      participants studied words paired with point values. There were two groups;
      participants either studied the words in the evening and were tested after a 12
      hr interval containing a full night of sleep, or studied the words in the morning
      and were tested after 12 hr of continuous daytime wake. Free recall (F(1,36) =
      19.35, p<.001) and recognition accuracy (F(1,36) = 7.59, p = .01) for words were
      better following sleep relative to wake. However there was no difference in the
      linear increase in the probability of delayed recall with increasing word value
      for sleep and wake groups (p = .74). Thus, while encoding may vary with the value
      of the to-be-learned item, sleep-dependent consolidation does not. 

PMID- 24130704
TI  - Hydrodynamic and longitudinal impedance analysis of cerebrospinal fluid dynamics
      at the craniovertebral junction in type I Chiari malformation.
AB  - Elevated or reduced velocity of cerebrospinal fluid (CSF) at the craniovertebral
      junction (CVJ) has been associated with type I Chiari malformation (CMI). Thus,
      quantification of hydrodynamic parameters that describe the CSF dynamics could
      help assess disease severity and surgical outcome. In this study, we describe the
      methodology to quantify CSF hydrodynamic parameters near the CVJ and upper
      cervical spine utilizing subject-specific computational fluid dynamics (CFD)
      simulations based on in vivo MRI measurements of flow and geometry. Hydrodynamic
      parameters were computed for a healthy subject and two CMI patients both pre- and
      post-decompression surgery to determine the differences between cases. For the
      first time, we present the methods to quantify longitudinal impedance (LI) to CSF
      motion, a subject-specific hydrodynamic parameter that may have value to help
      quantify the CSF flow blockage severity in CMI. In addition, the following
      hydrodynamic parameters were quantified for each case: maximum velocity in
      systole and diastole, Reynolds and Womersley number, and peak pressure drop
      during the CSF cardiac flow cycle. The following geometric parameters were
      quantified: cross-sectional area and hydraulic diameter of the spinal
      subarachnoid space (SAS). The mean values of the geometric parameters increased
      post-surgically for the CMI models, but remained smaller than the healthy
      volunteer. All hydrodynamic parameters, except pressure drop, decreased post
      surgically for the CMI patients, but remained greater than in the healthy case.
      Peak pressure drop alterations were mixed. To our knowledge this study represents
      the first subject-specific CFD simulation of CMI decompression surgery and
      quantification of LI in the CSF space. Further study in a larger patient and
      control group is needed to determine if the presented geometric and/or
      hydrodynamic parameters are helpful for surgical planning. 

PMID- 24130705
TI  - Distinguishing ichthyoses by protein profiling.
AB  - To explore the usefulness of protein profiling for characterization of
      ichthyoses, we here determined the profile of human epidermal stratum corneum by
      shotgun proteomics. Samples were analyzed after collection on tape circles from
      six anatomic sites (forearm, palm, lower leg, forehead, abdomen, upper back),
      demonstrating site-specific differences in profiles. Additional samples were
      collected from the forearms of subjects with ichthyosis vulgaris (filaggrin (FLG)
      deficiency), recessive X-linked ichthyosis (steroid sulfatase (STS) deficiency)
      and autosomal recessive congenital ichthyosis type lamellar ichthyosis
      (transglutaminase 1 (TGM1) deficiency). The ichthyosis protein expression
      patterns were readily distinguishable from each other and from phenotypically
      normal epidermis. In general, the degree of departure from normal was lower from
      ichthyosis vulgaris than from lamellar ichthyosis, parallel to the severity of
      the phenotype. Analysis of samples from families with ichthyosis vulgaris and
      concomitant modifying gene mutations (STS deficiency, GJB2 deficiency) permitted
      correlation of alterations in protein profile with more complex genetic
      constellations. 

PMID- 24130706
TI  - Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors
      in thioacetamide-induced liver disease.
AB  - Galectin-3 protein is critical to the development of liver fibrosis because
      galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we
      examined the ability of novel complex carbohydrate galectin inhibitors to treat
      toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by
      intraperitoneal injections with thioacetamide (TAA) and groups were treated with
      vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan).
      In initial experiments, 4 weeks of treatment with GR-MD-02 following completion
      of 8 weeks of TAA significantly reduced collagen content by almost 50% based on
      Sirius red staining. Rats were then exposed to more intense and longer TAA
      treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11.
      TAA rats treated with vehicle developed extensive fibrosis and pathological stage
      6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or
      GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8-11 led to marked
      reduction in fibrosis with reduction in portal and septal galectin-3 positive
      macrophages and reduction in portal pressure. Vehicle-treated animals had
      cirrhosis whereas in the treated animals the fibrosis stage was significantly
      reduced, with evidence of resolved or resolving cirrhosis and reduced portal
      inflammation and ballooning. In this model of toxin-induced liver fibrosis,
      treatment with two galectin protein inhibitors with different chemical
      compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin
      3 expressing portal and septal macrophages, and reduced portal pressure. These
      findings suggest a potential role of these drugs in human liver fibrosis and
      cirrhosis. 

PMID- 24130707
TI  - It's not just conflict that motivates killing of orangutans.
AB  - We investigated why orangutans are being killed in Kalimantan, Indonesia, and the
      role of conflict in these killings. Based on an analysis of interview data from
      over 5,000 respondents in over 450 villages, we also assessed the socio
      ecological factors associated with conflict and non-conflict killings. Most
      respondents never kill orangutans. Those who reported having personally killed an
      orangutan primarily did so for non-conflict reasons; for example, 56% of these
      respondents said that the reason they had killed an orangutan was to eat it. Of
      the conflict-related reasons for killing, the most common reasons orangutans were
      killed was fear of orangutans or in self-defence. A similar pattern was evident
      among reports of orangutan killing by other people in the villages. Regression
      analyses indicated that religion and the percentage of intact forest around
      villages were the strongest socio-ecological predictors of whether orangutans
      were killed for conflict or non-conflict related reasons. Our data indicate that
      between 44,170 and 66,570 orangutans were killed in Kalimantan within the
      respondents' active hunting lifetimes: between 12,690 and 29,024 for conflict
      reasons (95%CI) and between 26,361 and 41,688 for non-conflict reasons (95% CI).
      These findings confirm that habitat protection alone will not ensure the survival
      of orangutans in Indonesian Borneo, and that effective reduction of orangutan
      killings is urgently needed. 

PMID- 24130708
TI  - The signal sequence influences post-translational ER translocation at distinct
      stages.
AB  - The metazoan Sec61 translocon transports polypeptides into and across the
      membrane of the endoplasmic reticulum via two major routes, a well-established co
      translational pathway and a post-translational alternative. We have used two
      model substrates to explore the elements of a secretory protein precursor that
      preferentially direct it towards a co- or post-translational pathway for ER
      translocation. Having first determined the capacity of precursors to enter ER
      derived microsomes post-translationally, we then exploited semi-permeabilized
      mammalian cells specifically depleted of key membrane components using siRNA to
      address their contribution to the membrane translocation process. These studies
      suggest precursor chain length is a key factor in the post-translational
      translocation at the mammalian ER, and identify Sec62 and Sec63 as important
      components acting on this route. This role for Sec62 and Sec63 is independent of
      the signal sequence that delivers the precursor to the ER. However, the signal
      sequence can influence the subsequent membrane translocation process, conferring
      sensitivity to a small molecule inhibitor and dictating reliance on the molecular
      chaperone BiP. Our data support a model where secretory protein precursors that
      fail to engage the signal recognition particle, for example because they are
      short, are delivered to the ER membrane via a distinct route that is dependent
      upon both Sec62 and Sec63. Although this requirement for Sec62 and Sec63 is
      unaffected by the specific signal sequence that delivers a precursor to the ER,
      this region can influence subsequent events, including both Sec61 mediated
      transport and the importance of BiP for membrane translocation. Taken together,
      our data suggest that an ER signal sequence can regulate specific aspects of
      Sec61 mediated membrane translocation at a stage following Sec62/Sec63 dependent
      ER delivery. 

PMID- 24130709
TI  - Multiple sclerosis susceptibility genes: associations with relapse severity and
      recovery.
AB  - OBJECTIVE: Patients with early multiple sclerosis (MS) have stereotyped attack
      severity and recovery. We sought to determine if polymorphisms in MS
      susceptibility genes are associated with these attack features or with the risk
      of a second attack. METHODS: 503 white subjects evaluated within a year of MS
      onset were included in the study. The severity of and recovery from the first two
      attacks were determined based on published definitions. Seventeen MS
      susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each
      polymorphism was evaluated in multivariate ordinal models, adjusted for the other
      polymorphisms, for its association with attack severity and recovery. We also
      assessed if these polymorphisms were associated with increased risk of a second
      attack. RESULTS: The MPHOSPH9 polymorphism was associated with greater attack
      severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the
      RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack
      severity. The CD6 polymorphism tended to be associated with increased odds of
      worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who
      were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less
      severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of
      greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms
      tended to be associated with having a second event within a year. CONCLUSIONS:
      Some MS susceptibility polymorphisms may be associated with attack severity,
      recovery, or frequency. Further characterization of these genes may lead to a
      better understanding of MS pathogenesis and to a more individualized treatment
      approach.

PMID- 24130710
TI  - A positive trajectory for corals atLittle Cayman Island.
AB  - Coral reefs are damaged by natural disturbances and local and global
      anthropogenic stresses. As stresses intensify, so do debates about whether reefs
      will recover after significant damage. True headway in this debate requires
      documented temporal trajectories for coral assemblages subjected to various
      combinations of stresses; therefore, we report relevant changes in coral
      assemblages at Little Cayman Island. Between 1999 and 2012, spatiotemporal
      patterns in cover, densities of juveniles and size structure of assemblages were
      documented inside and outside marine protected areas using transects, quadrats
      and measurements of maximum diameters. Over five years, bleaching and disease
      caused live cover to decrease from 26% to 14%, with full recovery seven years
      later. Juvenile densities varied, reaching a maximum in 2010. Both patterns were
      consistent within and outside protected areas. In addition, dominant coral
      species persisted within and outside protected areas although their size
      frequency distributions varied temporally and spatially. The health of the coral
      assemblage and the similarity of responses across levels of protection suggested
      that negligible anthropogenic disturbance at the local scale was a key factor
      underlying the observed resilience. 

PMID- 24130711
TI  - Targeting fungal genes by diced siRNAs: a rapid tool to decipher gene function in
      Aspergillus nidulans.
AB  - BACKGROUND: Gene silencing triggered by chemically synthesized small interfering
      RNAs (siRNAs) has become a powerful tool for deciphering gene function in many
      eukaryotes. However, prediction and validation of a single siRNA duplex specific
      to a target gene is often ineffective. RNA interference (RNAi) with synthetic
      siRNA suffers from lower silencing efficacy, off-target effects and is cost
      intensive, especially for functional genomic studies. With the explosion of
      fungal genomic information, there is an increasing need to analyze gene function
      in a rapid manner. Therefore, studies were performed in order to investigate the
      efficacy of gene silencing induced by RNase III-diced-siRNAs (d-siRNA) in model
      filamentous fungus, Aspergillus nidulans. METHODOLOGY/PRINCIPAL FINDINGS: Stable
      expression of heterologous reporter gene in A. nidulans eases the examination of
      a new RNAi-induction route. Hence, we have optimized Agrobacterium tumefaciens
      mediated transformation (AMT) of A. nidulans for stable expression of sGFP gene.
      This study demonstrates that the reporter GFP gene stably introduced into A.
      nidulans can be effectively silenced by treatment of GFP-d-siRNAs. We have shown
      the down-regulation of two endogenous genes, AnrasA and AnrasB of A. nidulans by
      d-siRNAs. We have also elucidated the function of an uncharacterized Ras homolog,
      rasB gene, which was found to be involved in hyphal growth and development.
      Further, silencing potency of d-siRNA was higher as compared to synthetic siRNA
      duplex, targeting AnrasA. Silencing was shown to be sequence-specific, since
      expression profiles of other closely related Ras family genes in d-siRNA treated
      AnrasA and AnrasB silenced lines exhibited no change in gene expression.
      CONCLUSIONS/SIGNIFICANCE: We have developed and applied a fast, specific and
      efficient gene silencing approach for elucidating gene function in A. nidulans
      using d-siRNAs. We have also optimized an efficient AMT in A. nidulans, which is
      useful for stable integration of transgenes.

PMID- 24130712
TI  - Positional signaling and expression of ENHANCER OF TRY AND CPC1 are tuned to
      increase root hair density in response to phosphate deficiency in Arabidopsis
      thaliana.
AB  - Phosphate (Pi) deficiency induces a multitude of responses aimed at improving the
      acquisition of Pi, including an increased density of root hairs. To understand
      the mechanisms involved in Pi deficiency-induced alterations of the root hair
      phenotype in Arabidopsis (Arabidopsis thaliana), we analyzed the patterning and
      length of root epidermal cells under control and Pi-deficient conditions in wild
      type plants and in four mutants defective in the expression of master regulators
      of cell fate, CAPRICE (CPC), ENHANCER OF TRY AND CPC 1 (ETC1), WEREWOLF (WER) and
      SCRAMBLED (SCM). From this analysis we deduced that the longitudinal cell length
      of root epidermal cells is dependent on the correct perception of a positional
      signal ('cortical bias') in both control and Pi-deficient plants; mutants
      defective in the receptor of the signal, SCM, produced short cells characteristic
      of root hair-forming cells (trichoblasts). Simulating the effect of cortical bias
      on the time-evolving probability of cell fate supports a scenario in which a
      compromised positional signal delays the time point at which non-hair cells opt
      out the default trichoblast pathway, resulting in short, trichoblast-like non
      hair cells. Collectively, our data show that Pi-deficient plants increase root
      hair density by the formation of shorter cells, resulting in a higher frequency
      of hairs per unit root length, and additional trichoblast cell fate assignment
      via increased expression of ETC1. 

PMID- 24130713
TI  - Evaluation of the replication, pathogenicity, and immunogenicity of avian
      paramyxovirus (APMV) serotypes 2, 3, 4, 5, 7, and 9 in rhesus macaques.
AB  - Avian paramyxoviruses (APMV) serotypes 1-9 are frequently isolated from domestic
      and wild birds worldwide. APMV-1 (also called Newcastle disease virus, NDV) is
      attenuated in non-human primates and is being developed as a candidate human
      vaccine vector. The vector potential of the other serotypes was unknown. In the
      present study, we evaluated nine different biologically- or recombinantly-derived
      APMV strains for the ability to replicate and cause disease in rhesus macaque
      model. Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, 
      5, -7 and -9. Another virus was a recombinant (r) version of wt APMV-4. The
      remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F
      cleavage site had been modified to be multi-basic. Rhesus macaques were
      inoculated intranasally and intratracheally and monitored for clinical disease,
      virus shedding from the upper and lower respiratory tract, and seroconversion.
      Virus shedding was not detected for wt APMV-5. Very limited shedding was detected
      for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals. Shedding by
      the other viruses was detected in every infected animal, and usually from both
      the upper and lower respiratory tract. In particular, shedding over a number of
      days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified
      rAPMV-7. Modification of the F protein cleavage site appeared to increase
      shedding by wt rAPMV-2 and marginally by wt rAPMV-4. All APMVs except wt APMV-5
      induced a virus-specific serum antibody response in all infected animals. None of
      the animals exhibited any clinical disease signs. These results indicate that
      APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are
      moderately-to-highly restricted, depending on the serotype. This suggests that
      they are not likely to significantly infect primates in nature, and represent
      promising attenuated candidates for vector development. 

PMID- 24130714
TI  - Contrasting genetic structure among populations of two amphidromous fish species
      (Sicydiinae) in the Central West Pacific.
AB  - Both present-day and past processes can shape connectivity of populations.
      Pleistocene vicariant events and dispersal have shaped the present distribution
      and connectivity patterns of aquatic species in the Indo-Pacific region. In
      particular, the processes that have shaped distribution of amphidromous goby
      species still remain unknown. Previous studies show that phylogeographic breaks
      are observed between populations in the Indian and Pacific Oceans where the
      shallow Sunda shelf constituted a geographical barrier to dispersal, or that the
      large spans of open ocean that isolate the Hawaiian or Polynesian Islands are
      also barriers for amphidromous species even though they have great dispersal
      capacity. Here we assess past and present genetic structure of populations of two
      amphidromous fish (gobies of the Sicydiinae) that are widely distributed in the
      Central West Pacific and which have similar pelagic larval durations. We analysed
      sections of mitochondrial COI, Cytb and nuclear Rhodospine genes in individuals
      sampled from different locations across their entire known range. Similar to
      other Sicydiinae fish, intraspecific mtDNA genetic diversity was high for all
      species (haplotype diversity between 0.9-0.96). Spatial analyses of genetic
      variation in Sicyopus zosterophorum demonstrated strong isolation across the
      Torres Strait, which was a geologically intermittent land barrier linking
      Australia to Papua New Guinea. There was a clear genetic break between the
      northwestern and the southwestern clusters in Si. zosterophorum (phiST = 0.67502
      for COI) and coalescent analyses revealed that the two populations split at 306
      Kyr BP (95% HPD 79-625 Kyr BP), which is consistent with a Pleistocene separation
      caused by the Torres Strait barrier. However, this geographical barrier did not
      seem to affect Sm. fehlmanni. Historical and demographic hypotheses are raised to
      explain the different patterns of population structure and distribution between
      these species. Strategies aiming to conserve amphidromous fish should consider
      the presence of cryptic evolutionary lineages to prevent stock depletion. 

PMID- 24130716
TI  - Understanding the sustainability of retail food recovery.
AB  - In this paper we study the simultaneous problems of food waste and hunger in the
      context of food (waste) rescue and redistribution as a means for mitigating
      hunger. To this end, we develop an empirical model that can be used in Monte
      Carlo simulations to study the dynamics of the underlying problem. Our model's
      parameters are derived from a data set provided by a large food bank and food
      rescue organization in north central Colorado. We find that food supply is a non
      parametric heavy-tailed process that is well modeled with an extreme value peaks
      over threshold model. Although the underlying process is stochastic, the basic
      approach of food rescue and redistribution to meet hunger demand appears to be
      feasible. The ultimate sustainability of this model is intimately tied to the
      rate at which food expires and hence the ability to preserve and quickly
      transport and redistribute food. The cost of the redistribution is related to the
      number and density of participating suppliers. The results show that costs can be
      reduced (and supply increased) simply by recruiting additional donors to
      participate. With sufficient funding and manpower, a significant amount of food
      can be rescued from the waste stream and used to feed the hungry. 

PMID- 24130715
TI  - The neural correlates of mindful awareness: a possible buffering effect on
      anxiety-related reduction in subgenual anterior cingulate cortex activity.
AB  - BACKGROUND: Human personality consists of two fundamental elements character and
      temperament. Character allays automatic and preconceptual emotional responses
      determined by temperament. However, the neurobiological basis of character and
      its interplay with temperament remain elusive. Here, we examined character
      temperament interplay and explored the neural basis of character, with a
      particular focus on the subgenual anterior cingulate cortex extending to a
      ventromedial portion of the prefrontal cortex (sgACC/vmPFC). METHODS: Resting
      brain glucose metabolism (GM) was measured using [(18)F] fluorodeoxyglucose
      positron emission tomography in 140 healthy adults. Personality traits were
      assessed using the Temperament and Character Inventory. Regions of interest (ROI)
      analysis and whole-brain analysis were performed to examine a combination effect
      of temperament and character on the sgACC/vmPFC and to explore the neural
      correlates of character, respectively. RESULTS: Harm avoidance (HA), a
      temperament trait (i.e., depressive, anxious, vulnerable), showed a significant
      negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a
      character trait (i.e., intuitive, judicious, spiritual), exhibited a significant
      positive effect on GM in the same region (HA beta = -0.248, p = 0.003; ST: beta =
      0.250, p = 0.003). In addition, when coupled with strong ST, individuals with
      strong HA maintained the sgACC/vmPFC GM level comparable to the level of those
      with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis
      revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak
      voxel at x = -8, y = 32, z = -8, k = 423, Z = 4.41, corrected p (FDR) = 0.030).
      CONCLUSION: The current findings indicate that the sgACC/vmPFC might play a
      critical role in mindful awareness to something beyond as well as in emotional
      regulation. Developing a sense of mindfulness may temper exaggerated emotional
      responses in individuals with a risk for or having anxiety and depressive
      disorders.

PMID- 24130717
TI  - Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable
      metabolic modulation including antihypertensive effect on a mouse model of human
      metabolic disorders with visceral obesity.
AB  - Accumulating evidence indicates that metabolic dysfunction with visceral obesity
      is a major medical problem associated with the development of hypertension, type
      2 diabetes (T2DM) and dyslipidemia, and ultimately severe cardiovascular and
      renal disease. Therefore, an effective anti-obesity treatment with a concomitant
      improvement in metabolic profile is important for the treatment of metabolic
      dysfunction with visceral obesity. Bofu-tsu-shosan (BOF) is one of oriental
      herbal medicine and is clinically available to treat obesity in Japan. Although
      BOF is a candidate as a novel therapeutic strategy to improve metabolic
      dysfunction with obesity, the mechanism of its beneficial effect is not fully
      elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy
      mice, a model of human metabolic disorders with obesity. Chronic treatment of
      KKAy mice with BOF persistently decreased food intake, body weight gain, low
      density lipoprotein cholesterol and systolic blood pressure. In addition, both
      tissue weight and cell size of white adipose tissue (WAT) were decreased, with
      concomitant increases in the expression of adiponectin and peroxisome
      proliferator-activated receptors genes in WAT as well as the circulating
      adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling
      protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature
      were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form
      of orexigenic hormone, and short-term food intake were significantly decreased by
      single bolus administration of BOF. These results indicate that BOF exerts a
      combinatorial favorable metabolic modulation including antihypertensive effect,
      at least partially, via its beneficial effect on adipose tissue function and its
      appetite-inhibitory property through suppression on the ghrelin system. 

PMID- 24130718
TI  - Association of multiple sclerosis susceptibility variants and early attack
      location in the CNS.
AB  - OBJECTIVE: The anatomic location of subsequent relapses in early multiple
      sclerosis (MS) appears to be predicted by the first attack location. We sought to
      determine if genetic polymorphisms associated with MS susceptibility are
      associated with attack location. METHODS: 17 genome-wide association study
      identified MS susceptibility polymorphisms were genotyped in 503 white, non
      Hispanic patients seen within a year of MS onset. Their association with the CNS
      location of the first two MS attacks was assessed in multivariate repeated
      measures analyses (generalized estimating equations with robust standard errors).
      RESULTS: The IL12A polymorphism was independently associated with increased odds
      of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009),
      as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The
      IL7R polymorphism was associated with reduced odds of attacks involving the
      brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the
      TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of
      optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034).
      Several other genes showed trends for association with attack location.
      CONCLUSIONS: Some of the MS susceptibility genes may be associated with MS attack
      location. The IL12A polymorphism is of particular interest given that interferon
      beta therapy appears to influence IL12 levels. These findings may lead to
      improved understanding of MS pathogenesis and treatment.

PMID- 24130719
TI  - LED-fluorescence microscopy for diagnosis of pulmonary tuberculosis under
      programmatic conditions in India.
AB  - BACKGROUND: Light-emitting diode fluorescence microscopy (LED-FM) has been shown
      to be more sensitive than conventional bright field microscopy using Ziehl
      Neelsen (ZN) stain in detecting sputum smear positive tuberculosis in controlled
      laboratory conditions. In 2012, Auramine O staining based LED-FM replaced
      conventional ZN microscopy in 200 designated microscopy centres (DMC) of medical
      colleges operating in collaboration with India's Revised National Tuberculosis
      Control Programme. We aimed to assess the impact of introduction of LED-FM
      services on sputum smear positive case detection under program conditions.
      METHODS: This was a before and after comparison study. In 15 randomly selected
      medical college DMCs, all presumptive TB patients who underwent sputum smear
      examination in the years 2011 (before LED-FM) and 2012 (after LED-FM) were
      compared. An additional 15 comparable DMCs that implemented conventional ZN
      sputum smear microscopy were also selected for comparison between 2011 and 2012.
      RESULTS: The proportion of presumptive TB patients (PTP)found sputum smear
      positive increased by 30%- from 13.6% (3432/25159) in 2011 to 17.8% (4706/26426)
      in 2012 (P value <0.01) in the sites that implemented LED-FM microscopy, whereas
      in DMCs where the ZN staining procedure is followed the proportion of sputum
      smear positive had remained unchanged (13.0%versus 12.6%;P value0.31).
      CONCLUSION: Use of LED-FM significantly increased the proportion of smear
      positive cases among presumptive TB patients under routine program conditions in
      high workload laboratories. The study provides operational evidence needed to
      scale-up the use of LED-FM in similar settings in India and beyond.

PMID- 24130720
TI  - Community structure and multi-modal oscillations in complex networks.
AB  - In many types of network, the relationship between structure and function is of
      great significance. We are particularly interested in community structures, which
      arise in a wide variety of domains. We apply a simple oscillator model to
      networks with community structures and show that waves of regular oscillation are
      caused by synchronised clusters of nodes. Moreover, we show that such global
      oscillations may arise as a direct result of network topology. We also observe
      that additional modes of oscillation (as detected through frequency analysis)
      occur in networks with additional levels of topological hierarchy and that such
      modes may be directly related to network structure. We apply the method in two
      specific domains (metabolic networks and metropolitan transport) demonstrating
      the robustness of our results when applied to real world systems. We conclude
      that (where the distribution of oscillator frequencies and the interactions
      between them are known to be unimodal) our observations may be applicable to the
      detection of underlying community structure in networks, shedding further light
      on the general relationship between structure and function in complex systems. 

PMID- 24130721
TI  - Potential risk of regional disease spread in West Africa through cross-border
      cattle trade.
AB  - BACKGROUND: Transboundary animal movements facilitate the spread of pathogens
      across large distances. Cross-border cattle trade is of economic and cultural
      importance in West Africa. This study explores the potential disease risk
      resulting from large-scale, cross-border cattle trade between Togo, Burkina Faso,
      Ghana, Benin, and Nigeria for the first time. METHODS AND PRINCIPAL FINDINGS: A
      questionnaire-based survey of livestock movements of 226 cattle traders was
      conducted in the 9 biggest cattle markets of northern Togo in February-March
      2012. More than half of the traders (53.5%) operated in at least one other
      country. Animal flows were stochastically simulated based on reported movements
      and the risk of regional disease spread assessed. More than three quarters
      (79.2%, range: 78.1-80.0%) of cattle flowing into the market system originated
      from other countries. Through the cattle market system of northern Togo, non
      neighbouring countries were connected via potential routes for disease spread.
      Even for diseases with low transmissibility and low prevalence in a given
      country, there was a high risk of disease introduction into other countries.
      CONCLUSIONS: By stochastically simulating data collected by interviewing cattle
      traders in northern Togo, this study identifies potential risks for regional
      disease spread in West Africa through cross-border cattle trade. The findings
      highlight that surveillance for emerging infectious diseases as well as control
      activities targeting endemic diseases in West Africa are likely to be ineffective
      if only conducted at a national level. A regional approach to disease
      surveillance, prevention and control is essential.

PMID- 24130722
TI  - A vaccinia virus recombinant transcribing an alphavirus replicon and expressing
      alphavirus structural proteins leads to packaging of alphavirus infectious single
      cycle particles.
AB  - Poxviruses and Alphaviruses constitute two promising viral vectors that have been
      used extensively as expression systems, or as vehicles for vaccine purposes.
      Poxviruses, like vaccinia virus (VV) are well-established vaccine vectors having
      large insertion capacity, excellent stability, and ease of administration. In
      turn, replicons derived from Alphaviruses like Semliki Forest virus (SFV) are
      potent protein expression and immunization vectors but stocks are difficult to
      produce and maintain. In an attempt to demonstrate the use of a Poxvirus as a
      means for the delivery of small vaccine vectors, we have constructed and
      characterized VV/SFV hybrid vectors. A SFV replicon cDNA was inserted in the VV
      genome and placed under the control of a VV early promoter. The replicon,
      transcribed from the VV genome as an early transcript, was functional, and thus
      capable of initiating its own replication and transcription. Further, we
      constructed a VV recombinant additionally expressing the SFV structural proteins
      under the control of a vaccinia synthetic early/late promoter. Infection with
      this recombinant produced concurrent transcription of the replicon and expression
      of SFV structural proteins, and led to the generation of replicon-containing SFV
      particles that were released to the medium and were able to infect additional
      cells. This combined VV/SFV system in a single virus allows the use of VV as a
      SFV delivery vehicle in vivo. The combination of two vectors, and the possibility
      of generating in vivo single-cycle, replicon containing alphavirus particles, may
      open new strategies in vaccine development or in the design of oncolytic viruses.

PMID- 24130723
TI  - Combination treatments with the PKC inhibitor, enzastaurin, enhance the
      cytotoxicity of the anti-mesothelin immunotoxin, SS1P.
AB  - Activated protein kinase C (PKC) contributes to tumor survival and proliferation,
      provoking the development of inhibitory agents as potential cancer therapeutics.
      Immunotoxins are antibody-based recombinant proteins that employ antibody
      fragments for cancer targeting and bacterial toxins as the cytotoxic agent.
      Pseudomonas exotoxin-based immunotoxins act via the ADP-ribosylation of EF2
      leading to the enzymatic inhibition of protein synthesis. Combining PKC
      inhibitors with the immunotoxin SS1P, targeted to surface mesothelin, was
      undertaken to explore possible therapeutic strategies. Enzastaurin but not two
      other PKC inhibitors combined with SS1P to produce synergistic cell death via
      apoptosis. Mechanistic insights of the synergistic killing centered on the
      complete loss of the prosurvival Bcl2 protein, Mcl-1, the loss of AKT and the
      activation of caspase 3/7. Synergy was most evident when cells exhibited
      resistance to the immunotoxin alone. Further, because PKC inhibition by itself
      was not sufficient to enhance SS1P action, enzastaurin must target other kinases
      that are involved in the immunotoxin pathway. 

PMID- 24130724
TI  - Individual subject classification of mixed dementia from pure subcortical
      vascular dementia based on subcortical shape analysis.
AB  - Subcortical vascular dementia (SVaD), one of common causes of dementia, has
      concomitant Alzheimer's disease (AD) pathology in over 30%, termed "mixed
      dementia". Identifying mixed dementia from SVaD is important because potential
      amyloid-targeted therapies may be effective for treatment in mixed dementia. The
      purpose of this study was to discriminate mixed dementia from pure SVaD using
      magnetic resonance imaging (MRI). We measured brain amyloid deposition using the
      11C-Pittsburgh compound B positron emission tomography (PiB-PET) in 68 patients
      with SVaD. A PiB retention ratio greater than 1.5 was considered PiB(+).
      Hippocampal and amygdalar shape were used in the incremental learning method to
      discriminate mixed dementia from pure SVaD because these structures are known to
      be prominently involved by AD pathologies. Among 68 patients, 23 (33.8%) patients
      were positive for PiB binding. With use of hippocampal shape analysis alone,
      PiB(+) SVaD could be discriminated from PiB(-) SVaD with 77.9% accuracy (95.7%
      sensitivity and 68.9% specificity). With use of amygdalar shape, the
      discrimination accuracy was 75.0% (87.0% sensitivity and 68.9% specificity). When
      hippocampal and amygdalar shape were analyzed together, accuracy increased to
      82.4% (95.7% sensitivity and 75.6% specificity). An incremental learning method
      using hippocampal and amygdalar shape distinguishes mixed dementia from pure
      SVaD. Furthermore, our results suggest that amyloid pathology and vascular
      pathology have different effects on the shape of the hippocampus and amygdala. 

PMID- 24130725
TI  - DNA fingerprinting of pearls to determine their origins.
AB  - We report the first successful extraction of oyster DNA from a pearl and use it
      to identify the source oyster species for the three major pearl-producing oyster
      species Pinctada margaritifera, P. maxima and P. radiata. Both mitochondrial and
      nuclear gene fragments could be PCR-amplified and sequenced. A polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assay in the
      internal transcribed spacer (ITS) region was developed and used to identify 18
      pearls of unknown origin. A micro-drilling technique was developed to obtain
      small amounts of DNA while maintaining the commercial value of the pearls. This
      DNA fingerprinting method could be used to document the source of historic pearls
      and will provide more transparency for traders and consumers within the pearl
      industry. 

PMID- 24130726
TI  - Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during
      the post-partum period in pregnant women with chronic hepatitis C.
AB  - This study analyses the evolution of liver disease in women with chronic
      hepatitis C during the third trimester of pregnancy and the post-partum period,
      as a natural model of immune modulation and reconstitution. Of the 122 mothers
      recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV
      ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at
      delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either
      Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L;
      P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers
      also presented a significant decrease in serum HCV-RNA levels in the post
      delivery period (P<0.001) and this event was concomitant with an increase in Th1
      cytokine levels (INFgamma, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the
      other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations
      in either of these parameters. However, they did present higher Th1 cytokine
      levels in the partum period (INFgamma and IL2, P<0.05) than both the Type-A and
      the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute
      a risk factor associated with HCV vertical transmission. It is concluded that
      differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the
      postpartum period might be due to different ratios of Th1 cytokine production. In
      the Type-B women, the high partum levels of Th1 cytokines and the absence of post
      partum variation in ALT and HCV-RNA levels may be related to permanent Th1
      cytokine stimulation. 

PMID- 24130727
TI  - Chromatin compaction protects genomic DNA from radiation damage.
AB  - Genomic DNA is organized three-dimensionally in the nucleus, and is thought to
      form compact chromatin domains. Although chromatin compaction is known to be
      essential for mitosis, whether it confers other advantages, particularly in
      interphase cells, remains unknown. Here, we report that chromatin compaction
      protects genomic DNA from radiation damage. Using a newly developed solid-phase
      system, we found that the frequency of double-strand breaks (DSBs) in compact
      chromatin after ionizing irradiation was 5-50-fold lower than in decondensed
      chromatin. Since radical scavengers inhibited DSB induction in decondensed
      chromatin, condensed chromatin had a lower level of reactive radical generation
      after ionizing irradiation. We also found that chromatin compaction protects DNA
      from attack by chemical agents. Our findings suggest that genomic DNA compaction
      plays an important role in maintaining genomic integrity. 

PMID- 24130728
TI  - The effect of p38MAPK on cyclic stretch in human facial hypertrophic scar
      fibroblast differentiation.
AB  - Hypertrophic scars (HTS), the excessive deposition of scar tissue by fibroblasts,
      is one of the most common skin disorders. Fibroblasts derived from surgical scar
      tissue produce high levels of alpha-smooth muscle actin (alpha-SMA) and
      transforming growth factor-beta1 (TGF-beta1). However, the molecular mechanisms
      for this phenomenon is poorly understood. Thus, the purpose of this study was to
      evaluate the molecular mechanisms of HTS and their potential therapeutic
      implications. Fibroblasts derived from skin HTS were cultured and characterized
      in vitro. The fibroblasts were synchronized and randomly assigned to two groups:
      cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK
      inhibitor). Cyclic stretch at 10% strain was applied at a loading frequency of 10
      cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation) for 0
      h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the
      expression of alpha-SMA and TGF-beta1 mRNA and protein and the phosphorylation of
      p38MAPK. SB203580 reversed these effects and caused a decrease in matrix
      contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK
      inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its
      inhibition is suggested as a novel therapeutic strategy for HTS. 

PMID- 24130729
TI  - A prospective epidemiological study of acute mountain sickness in Nepalese
      pilgrims ascending to high altitude (4380 m).
AB  - BACKGROUND: Each year, thousands of pilgrims travel to the Janai Purnima festival
      in Gosainkunda, Nepal (4380 m), ascending rapidly and often without the aid of
      pharmaceutical prophylaxis. METHODS: During the 2012 Janai Purnima festival, 538
      subjects were recruited in Dhunche (1950 m) before ascending to Gosainkunda.
      Through interviews, subjects provided demographic information, ratings of AMS
      symptoms (Lake Louise Scores; LLS), ascent profiles, and strategies for
      prophylaxis. RESULTS: In the 491 subjects (91% follow-up rate) who were assessed
      upon arrival at Gosainkunda, the incidence of AMS was 34.0%. AMS was more common
      in females than in males (RR = 1.57; 95% CI = 1.23, 2.00), and the AMS incidence
      was greater in subjects >35 years compared to subjects <=35 years (RR = 1.63; 95%
      CI = 1.36, 1.95). There was a greater incidence of AMS in subjects who chose to
      use garlic as a prophylactic compared to those who did not (RR = 1.69; 95% CI =
      1.26, 2.28). Although the LLS of brothers had a moderate correlation (intraclass
      correlation = 0.40, p = 0.023), sibling AMS status was a weak predictor of AMS.
      CONCLUSIONS: The incidence of AMS upon reaching 4380 m was 34% in a large
      population of Nepalese pilgrims. Sex, age, and ascent rate were significant
      factors in the development of AMS, and traditional Nepalese remedies were
      ineffective in the prevention of AMS.

PMID- 24130730
TI  - Habitat association and conservation implications of endangered Francois' langur
      (Trachypithecus francoisi).
AB  - Francois' langur (Trachypithecus francoisi) is an endangered primate and endemic
      to the limestone forests of the tropical and subtropical zone of northern Vietnam
      and South-west China with a population of about 2,000 individuals. Conservation
      efforts are hampered by limited knowledge of habitat preference in its main
      distribution area. We surveyed the distribution of Francois' langur and modeled
      the relationship between the probability of use and habitat features in Mayanghe
      National Nature Reserve, Guizhou, China. The main objectives of this study were
      to provide quantitative information on habitat preference, estimating the
      availability of suitable habitat, and providing management guidelines for the
      effective conservation of this species. By comparing 92 used locations with
      habitat available in the reserve, we found that Francois' langur was mainly
      distributed along valleys and proportionally, used bamboo forests and mixed
      conifer-broadleaf forests more than their availability, whereas they tended to
      avoid shrubby areas and coniferous forests. The langur tended to occur at sites
      with lower elevation, steeper slope, higher tree canopy density, and a close
      distance to roads and water. The habitat occupancy probability was best modeled
      by vegetation type, vegetation coverage, elevation, slope degree, distances to
      nearest water, paved road, and farmland edge. The suitable habitat in this
      reserve concentrated in valleys and accounted for about 25% of the total reserve
      area. Our results showed that Francois' langur was not only restricted at the
      landscapes level at the regions with karst topography, limestone cliffs, and
      caves, but it also showed habitat preference at the local scale. Therefore, the
      protection and restoration of the langur preferred habitats such as mixed conifer
      broadleaf forests are important and urgent for the conservation of this declining
      species. 

PMID- 24130732
TI  - Quantitative and qualitative approaches to identifying migration chronology in a
      continental migrant.
AB  - The degree to which extrinsic factors influence migration chronology in North
      American waterfowl has not been quantified, particularly for dabbling ducks.
      Previous studies have examined waterfowl migration using various methods,
      however, quantitative approaches to define avian migration chronology over broad
      spatio-temporal scales are limited, and the implications for using different
      approaches have not been assessed. We used movement data from 19 female adult
      mallards (Anas platyrhynchos) equipped with solar-powered global positioning
      system satellite transmitters to evaluate two individual level approaches for
      quantifying migration chronology. The first approach defined migration based on
      individual movements among geopolitical boundaries (state, provincial,
      international), whereas the second method modeled net displacement as a function
      of time using nonlinear models. Differences in migration chronologies identified
      by each of the approaches were examined with analysis of variance. The
      geopolitical method identified mean autumn migration midpoints at 15 November
      2010 and 13 November 2011, whereas the net displacement method identified
      midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring
      migration were 3 April 2011 and 20 March 2012 using the geopolitical method and
      31 March 2011 and 22 March 2012 using the net displacement method. The duration,
      initiation date, midpoint, and termination date for both autumn and spring
      migration did not differ between the two individual level approaches. Although we
      did not detect differences in migration parameters between the different
      approaches, the net displacement metric offers broad potential to address
      questions in movement ecology for migrating species. Ultimately, an objective
      definition of migration chronology will allow researchers to obtain a
      comprehensive understanding of the extrinsic factors that drive migration at the
      individual and population levels. As a result, targeted conservation plans can be
      developed to support planning for habitat management and evaluation of long-term
      climate effects. 

PMID- 24130731
TI  - Lactobacillus acidophilus alleviates platelet-activating factor-induced
      inflammatory responses in human intestinal epithelial cells.
AB  - Probiotics have been used as alternative prevention and therapy modalities in
      intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and
      necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the
      production of diverse lipid mediators, including platelet-activating factor (PAF)
      that mediate inflammatory responses in the disease. PAF is known to activate NF
      kappaB, however, the mechanisms of PAF-induced inflammation are not fully
      defined. We have recently described a novel PAF-triggered pathway of NF-kappaB
      activation and IL-8 production in intestinal epithelial cells (IECs), requiring
      the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3
      and MALT1. The current studies examined the potential role of the probiotic
      Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-kappaB
      activation and IL-8 production in IECs. PAF treatment (5 uM*24 h) of NCM460 and
      Caco-2 cells significantly increased nuclear p65 NF-kappaB levels and IL-8
      secretion (2-3-fold, P<0.05), compared to control, which were blocked by
      pretreatment of the cells for 6 h with L. acidophilus (LA) or its culture
      supernatant (CS), followed by continued treatments with PAF for 24 h. LA-CS also
      attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10
      promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with
      CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced
      ubiquitination of IKKgamma. Efficacy of bacteria-free CS of LA in counteracting
      PAF-induced inflammatory cascade suggests that soluble factor(s) in the CS of LA
      mediate these effects. These results define a novel mechanism by which probiotics
      counteract PAF-induced inflammation in IECs. 

PMID- 24130733
TI  - ESAT-6 and HspX improve the effectiveness of BCG to induce human dendritic cells
      dependent Th1 and NK cells activation.
AB  - The limited efficacy of the BCG vaccine against tuberculosis is partly due to the
      missing expression of immunogenic proteins. We analyzed whether the addition to
      BCG of ESAT-6 and HspX, two Mycobacterium tuberculosis (Mtb) antigens, could
      enhance its capacity to activate human dendritic cells (DCs). BCG showed a weak
      ability to induce DC maturation, cytokine release, and CD4(+) lymphocytes and NK
      cells activation. The addition of ESAT-6 or HspX alone to BCG-stimulated DC did
      not improve these processes, whereas their simultaneous addition enhanced BCG
      dependent DC maturation and cytokine release, as well as the ability of BCG
      treated DCs to stimulate IFN-gamma release and CD69 expression by CD4(+)
      lymphocytes and NK cells. Addition of TLR2-blocking antibody decreased IL-12
      release by BCG-stimulated DCs incubated with ESAT-6 and HspX, as well as IFN
      gamma secretion by CD4(+) lymphocytes co-cultured with these cells. Moreover,
      HspX and ESAT-6 improved the capacity of BCG-treated DCs to induce the expression
      of memory phenotype marker CD45RO in naive CD4(+) T cells. Our results indicate
      that ESAT-6 and HspX cooperation enables BCG-treated human DCs to induce T
      lymphocyte and NK cell-mediated immune responses through TLR2-dependent IL-12
      secretion. Therefore ESAT-6 and HspX represent good candidates for improving the
      effectiveness of BCG vaccination. 

PMID- 24130734
TI  - Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas
      [corrected]..
AB  - Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either
      immunostimulatory or immunosuppressive functions depending on the context. In
      various murine tumor models including melanoma models, ectopic expression of IL
      27 has been shown to play an anti-tumoral role and to favor tumor regression. In
      this study, we investigated whether IL-27 might play a role in the development of
      melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic
      lesions (n = 82) representative of different stages of tumor progression. IL-27
      expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but
      was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in
      advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source
      of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous
      melanomas, its expression was maintained in metastatic lesions. These in situ
      data suggested that the immunosuppressive functions of IL-27 may dominate in
      human melanoma. Consistent with this hypothesis, we found that IL-27 could induce
      suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma
      cells, and that the in situ expression of IL-27 in melanoma correlated with those
      of PD-L1 and IL-10. 

PMID- 24130735
TI  - Placebo-suggestion modulates conflict resolution in the Stroop Task.
AB  - Here, we ask whether placebo-suggestion (without any form of hypnotic induction)
      can modulate the resolution of cognitive conflict. Naive participants performed a
      Stroop Task while wearing an EEG cap described as a "brain wave" machine. In
      Experiment 1, participants were made to believe that the EEG cap would either
      enhance or decrease their color perception and performance on the Stroop task. In
      Experiment 2, participants were explicitly asked to imagine that their color
      perception and performance would be enhanced or decreased (non-hypnotic
      imaginative suggestion). We observed effects of placebo-suggestion on Stroop
      interference on accuracy: interference was decreased with positive suggestion and
      increased with negative suggestion compared to baseline. Intra-individual
      variability was also increased under negative suggestion compared to baseline.
      Compliance with the instruction to imagine a modulation of performance, on the
      other hand, did not influence accuracy and only had a negative impact on response
      latencies and on intra-individual variability, especially in the congruent
      condition of the Stroop Task. Taken together, these results demonstrate that
      expectations induced by a placebo-suggestion can modulate our ability to resolve
      cognitive conflict, either facilitating or impairing response accuracy depending
      on the suggestion's contents. Our results also demonstrate a dissociation between
      placebo-suggestion and non-hypnotic imaginative suggestion. 

PMID- 24130736
TI  - The effect of dietary supplementation with spent cider yeast on the Swine distal
      gut microbiome.
AB  - BACKGROUND: There is an increasing need for alternatives to antibiotics for
      promoting animal health, given the increasing problems associated with antibiotic
      resistance. In this regard, we evaluated spent cider yeast as a potential
      probiotic for modifying the gut microbiota in weanling pigs using pyrosequencing
      of 16S rRNA gene libraries. METHODOLOGY AND PRINCIPAL FINDINGS: Piglets aged 24
      26 days were assigned to one of two study groups; control (n = 12) and treatment
      (n = 12). The control animals were fed with a basal diet and the treatment
      animals were fed with basal diet in combination with cider yeast supplement (500
      ml cider yeast containing ~7.6 log CFU/ml) for 21 days. Faecal samples were
      collected for 16s rRNA gene compositional analysis. 16S rRNA compositional
      sequencing analysis of the faecal samples collected from day 0 and day 21
      revealed marked differences in microbial diversity at both the phylum and genus
      levels between the control and treatment groups. This analysis confirmed that
      levels of Salmonella and Escherichia were significantly decreased in the
      treatment group, compared with the control (P<0.001). This data suggest a
      positive influence of dietary supplementation with live cider yeast on the
      microbial diversity of the pig distal gut. CONCLUSIONS/SIGNIFICANCE: The effect
      of dietary cider yeast on porcine gut microbial communities was characterized for
      the first time using 16S rRNA gene compositional sequencing. Dietary cider yeast
      can potentially alter the gut microbiota, however such changes depend on their
      endogenous microbiota that causes a divergence in relative response to that given
      diet.

PMID- 24130737
TI  - Adiponectin enhances the responsiveness of the olfactory system.
AB  - The peptide hormone adiponectin is secreted by adipose tissue and the circulating
      concentration is reversely correlated with body fat mass; it is considered as
      starvation signal. The observation that mature sensory neurons of the main
      olfactory epithelium express the adiponectin receptor 1 has led to the concept
      that adiponectin may affect the responsiveness of the olfactory system. In fact,
      electroolfactogram recordings from olfactory epithelium incubated with exogenous
      adiponectin resulted in large amplitudes upon odor stimulation. To determine
      whether the responsiveness of the olfactory sensory neurons was enhanced, we have
      monitored the odorant-induced expression of the immediate early gene Egr1. It was
      found that in an olfactory epithelium incubated with nasally applied adiponectin
      the number of Egr1 positive cells was significantly higher compared to controls,
      suggesting that adiponectin rendered the olfactory neurons more responsive to an
      odorant stimulus. To analyze whether the augmented responsiveness of sensory
      neurons was strong enough to elicit a higher neuronal activity in the olfactory
      bulb, the number of activated periglomerular cells of a distinct glomerulus was
      determined by monitoring the stimulus-induced expression of c-fos. The studies
      were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to
      visualize the corresponding glomerulus and to stimulate with a known ligand. The
      data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice
      the number of activated periglomerular neurons was significantly increased
      compared to controls. The results of this study indicate that adiponectin
      increases the responsiveness of the olfactory system, probably due to a higher
      responsiveness of olfactory sensory neurons. 

PMID- 24130738
TI  - AcalPred: a sequence-based tool for discriminating between acidic and alkaline
      enzymes.
AB  - The structure and activity of enzymes are influenced by pH value of their
      surroundings. Although many enzymes work well in the pH range from 6 to 8, some
      specific enzymes have good efficiencies only in acidic (pH<5) or alkaline (pH>9)
      solution. Studies have demonstrated that the activities of enzymes correlate with
      their primary sequences. It is crucial to judge enzyme adaptation to acidic or
      alkaline environment from its amino acid sequence in molecular mechanism
      clarification and the design of high efficient enzymes. In this study, we
      developed a sequence-based method to discriminate acidic enzymes from alkaline
      enzymes. The analysis of variance was used to choose the optimized discriminating
      features derived from g-gap dipeptide compositions. And support vector machine
      was utilized to establish the prediction model. In the rigorous jackknife cross
      validation, the overall accuracy of 96.7% was achieved. The method can correctly
      predict 96.3% acidic and 97.1% alkaline enzymes. Through the comparison between
      the proposed method and previous methods, it is demonstrated that the proposed
      method is more accurate. On the basis of this proposed method, we have built an
      online web-server called AcalPred which can be freely accessed from the website
      (http://lin.uestc.edu.cn/server/AcalPred). We believe that the AcalPred will
      become a powerful tool to study enzyme adaptation to acidic or alkaline
      environment. 

PMID- 24130739
TI  - Assessment of genetic correlation between bacterial cold water disease resistance
      and spleen index in a domesticated population of rainbow trout: identification of
      QTL on chromosome Omy19.
AB  - Selective breeding of animals for increased disease resistance is an effective
      strategy to reduce mortality in aquaculture. However, implementation of selective
      breeding programs is limited by an incomplete understanding of host resistance
      traits. We previously reported results of a rainbow trout selection program that
      demonstrated increased survival following challenge with Flavobacterium
      psychrophilum, the causative agent of bacterial cold water disease (BCWD).
      Mechanistic study of disease resistance identified a positive phenotypic
      correlation between post-challenge survival and spleen somatic-index (SI).
      Herein, we investigated the hypothesis of a genetic correlation between the two
      traits influenced by colocalizing QTL. We evaluated the inheritance and
      calculated the genetic correlation in five year-classes of odd- and even-year
      breeding lines. A total of 322 pedigreed families (n = 25,369 fish) were measured
      for disease resistance, and 251 families (n = 5,645 fish) were evaluated for SI.
      Spleen index was moderately heritable in both even-year (h(2)  = 0.56+/-0.18) and
      odd-year (h(2)  = 0.60+/-0.15) lines. A significant genetic correlation between
      SI and BCWD resistance was observed in the even-year line (rg  = 0.45+/-0.20, P =
      0.03) but not in the odd-year line (rg  = 0.16+/-0.12, P = 0.19). Complex
      segregation analyses of the even-year line provided evidence of genes with major
      effect on SI, and a genome scan of a single family, 2008132, detected three
      significant QTL on chromosomes Omy19, 16 and 5, in addition to ten suggestive
      QTL. A separate chromosome scan for disease resistance in family 2008132
      identified a significant BCWD QTL on Omy19 that was associated with time to death
      and percent survival. In family 2008132, Omy19 microsatellite alleles that
      associated with higher disease resistance also associated with increased spleen
      size raising the hypothesis that closely linked QTL contribute to the correlation
      between these traits. To our knowledge, this is the first estimation of spleen
      size heritability and evidence for genetic linkage with specific disease
      resistance in a teleost fish. 

PMID- 24130740
TI  - Long non-coding RNA expression profiling of mouse testis during postnatal
      development.
AB  - Mammalian testis development and spermatogenesis play critical roles in male
      fertility and continuation of a species. Previous research into the molecular
      mechanisms of testis development and spermatogenesis has largely focused on the
      role of protein-coding genes and small non-coding RNAs, such as microRNAs and
      piRNAs. Recently, it has become apparent that large numbers of long (>200 nt) non
      coding RNAs (lncRNAs) are transcribed from mammalian genomes and that lncRNAs
      perform important regulatory functions in various developmental processes.
      However, the expression of lncRNAs and their biological functions in post-natal
      testis development remain unknown. In this study, we employed microarray
      technology to examine lncRNA expression profiles of neonatal (6-day-old) and
      adult (8-week-old) mouse testes. We found that 8,265 lncRNAs were expressed above
      background levels during post-natal testis development, of which 3,025 were
      differentially expressed. Candidate lncRNAs were identified for further
      characterization by an integrated examination of genomic context, gene ontology
      (GO) enrichment of their associated protein-coding genes, promoter analysis for
      epigenetic modification, and evolutionary conservation of elements. Many lncRNAs
      overlapped or were adjacent to key transcription factors and other genes involved
      in spermatogenesis, such as Ovol1, Ovol2, Lhx1, Sox3, Sox9, Plzf, c-Kit, Wt1,
      Sycp2, Prm1 and Prm2. Most differentially expressed lncRNAs exhibited epigenetic
      modification marks similar to protein-coding genes and tend to be expressed in a
      tissue-specific manner. In addition, the majority of differentially expressed
      lncRNAs harbored evolutionary conserved elements. Taken together, our findings
      represent the first systematic investigation of lncRNA expression in the
      mammalian testis and provide a solid foundation for further research into the
      molecular mechanisms of lncRNAs function in mammalian testis development and
      spermatogenesis. 

PMID- 24130741
TI  - Electrostatic similarities between protein and small molecule ligands facilitate
      the design of protein-protein interaction inhibitors.
AB  - One of the underlying principles in drug discovery is that a biologically active
      compound is complimentary in shape and molecular recognition features to its
      receptor. This principle infers that molecules binding to the same receptor may
      share some common features. Here, we have investigated whether the electrostatic
      similarity can be used for the discovery of small molecule protein-protein
      interaction inhibitors (SMPPIIs). We have developed a method that can be used to
      evaluate the similarity of electrostatic potentials between small molecules and
      known protein ligands. This method was implemented in a software called EleKit.
      Analyses of all available (at the time of research) SMPPII structures indicate
      that SMPPIIs bear some similarities of electrostatic potential with the ligand
      proteins of the same receptor. This is especially true for the more polar
      SMPPIIs. Retrospective analysis of several successful SMPPIIs has shown the
      applicability of EleKit in the design of new SMPPIIs. 

PMID- 24130742
TI  - Too good to be true: rhesus monkeys react negatively to better-than-expected
      offers.
AB  - To succeed in a dynamically changing world, animals need to predict their
      environments. Humans, in fact, exhibit such a strong desire for consistency that
      one of the most well-established findings in social psychology is the effort
      people make to maintain consistency among their beliefs, attitudes, and behavior.
      However, displeasure with unpredictability leads to a potential paradox, because
      a positive outcome that exceeds one's expectations often leads to increased
      subjective value and positive affect, not the opposite. We tested the hypothesis
      that two evolutionarily-conserved evaluation processes underlie goal-directed
      behavior: (1) consistency, concerned with prediction errors, and (2) valuation,
      concerned with outcome utility. Rhesus monkeys (Macaca mulatta) viewed a food
      item and then were offered an identical, better, or worse food, which they could
      accept or reject. The monkeys ultimately accepted all offers, attesting to the
      influence of the valuation process. However, they were slower to accept the
      unexpected offers, and they exhibited aversive reactions, especially to the
      better-than-expected offers, repeatedly turning their heads and looking away
      before accepting the food item. Our findings (a) provide evidence for two
      separable evaluation processes in primates, consistency and value assessment, (b)
      reveal a direct relationship between consistency assessment and emotional
      processes, and (c) show that our wariness with events that are much better than
      expected is shared with other social primates. 

PMID- 24130743
TI  - Massively parallel DNA sequencing successfully identifies new causative mutations
      in deafness genes in patients with cochlear implantation and EAS.
AB  - Genetic factors, the most common etiology in severe to profound hearing loss, are
      one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic
      Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a
      CI/EAS in patients with certain deafness gene mutations indicates that genetic
      testing would be helpful in predicting CI/EAS outcomes and deciding treatment
      choices. However, because of the extreme genetic heterogeneity of deafness,
      clinical application of genetic information still entails difficulties. Target
      exon sequencing using massively parallel DNA sequencing is a new powerful
      strategy to discover rare causative genes in Mendelian disorders such as
      deafness. We used massive sequencing of the exons of 58 target candidate genes to
      analyze 8 (4 early-onset, 4 late-onset) Japanese CI/EAS patients, who did not
      have mutations in commonly found genes including GJB2, SLC26A4, or mitochondrial
      1555A>G or 3243A>G mutations. We successfully identified four rare causative
      mutations in the MYO15A, TECTA, TMPRSS3, and ACTG1 genes in four patients who
      showed relatively good auditory performance with CI including EAS, suggesting
      that genetic testing may be able to predict the performance after implantation. 

PMID- 24130744
TI  - Animal detection in natural images: effects of color and image database.
AB  - The visual system has a remarkable ability to extract categorical information
      from complex natural scenes. In order to elucidate the role of low-level image
      features for the recognition of objects in natural scenes, we recorded saccadic
      eye movements and event-related potentials (ERPs) in two experiments, in which
      human subjects had to detect animals in previously unseen natural images. We used
      a new natural image database (ANID) that is free of some of the potential
      artifacts that have plagued the widely used COREL images. Color and grayscale
      images picked from the ANID and COREL databases were used. In all experiments,
      color images induced a greater N1 EEG component at earlier time points than
      grayscale images. We suggest that this influence of color in animal detection may
      be masked by later processes when measuring reation times. The ERP results of
      go/nogo and forced choice tasks were similar to those reported earlier. The non
      animal stimuli induced bigger N1 than animal stimuli both in the COREL and ANID
      databases. This result indicates ultra-fast processing of animal images is
      possible irrespective of the particular database. With the ANID images, the
      difference between color and grayscale images is more pronounced than with the
      COREL images. The earlier use of the COREL images might have led to an
      underestimation of the contribution of color. Therefore, we conclude that the
      ANID image database is better suited for the investigation of the processing of
      natural scenes than other databases commonly used. 

PMID- 24130745
TI  - Collective phenomena and non-finite state computation in a human social system.
AB  - We investigate the computational structure of a paradigmatic example of
      distributed social interaction: that of the open-source Wikipedia community. We
      examine the statistical properties of its cooperative behavior, and perform model
      selection to determine whether this aspect of the system can be described by a
      finite-state process, or whether reference to an effectively unbounded resource
      allows for a more parsimonious description. We find strong evidence, in a
      majority of the most-edited pages, in favor of a collective-state model, where
      the probability of a "revert" action declines as the square root of the number of
      non-revert actions seen since the last revert. We provide evidence that the
      emergence of this social counter is driven by collective interaction effects,
      rather than properties of individual users.

PMID- 24130746
TI  - Raccoon social networks and the potential for disease transmission.
AB  - Raccoons are an important vector of rabies and other pathogens. The degree to
      which these pathogens can spread through a raccoon population should be closely
      linked to association rates between individual raccoons. Most studies of raccoon
      sociality have found patterns consistent with low levels of social connectivity
      within populations, thus the likelihood of direct pathogen transmission between
      raccoons is theoretically low. We used proximity detecting collars and social
      network metrics to calculate the degree of social connectivity in an urban
      raccoon population for purposes of estimating potential pathogen spread. In
      contrast to previous assumptions, raccoon social association networks were highly
      connected, and all individuals were connected to one large social network during
      15 out of 18 months of study. However, these metrics may overestimate the
      potential for a pathogen to spread through a population, as many of the social
      connections were based on relatively short contact periods. To more closely
      reflect varying probabilities of pathogen spread, we censored the raccoon social
      networks based on the total amount of time spent in close proximity between two
      individuals per month. As this time criteria for censoring the social networks
      increased from one to thirty minutes, corresponding measures of network
      connectivity declined. These findings demonstrate that raccoon populations are
      much more tightly connected than would have been predicted based on previous
      studies, but also point out that additional research is needed to calculate more
      precise transmission probabilities by infected individuals, and determine how
      disease infection changes normal social behaviors. 

PMID- 24130747
TI  - Comprehensive clinic-pathological characteristics of cervical cancer in
      southwestern China and the clinical significance of histological type and lymph
      node metastases in young patients.
AB  - OBJECTIVE: To analyze the clinic-pathological characteristics of women with
      cervical cancers in southwestern China and discuss the features and prognosis of
      young patients. METHODS: A retrospective study was performed, which consisted of
      1,543 patients diagnosed with cervical cancer and underwent treatment at West
      China Second University Hospital between November 2005 and December 2010. Among
      them, 154 young patients with surgical procedures between November 2005 and
      December 2008 were selected for a 5-year follow-up and prognostic analysis.
      RESULTS: The proportion of advanced FIGO stage in patients aged over 35 years was
      higher than in patients aged 35 years or younger (55.1% vs 38.8%, P<0.001), and
      strong correlation was found between FIGO stages and the postoperative
      pathological risk factors (P<0.05). 312 patients (20.2%) were under 35 years old
      in the last 5 years. The proportion of cervical adenocarcinoma remained high in
      young patients (13.6%), and young women with adenocarcinoma had a higher rate of
      LN metastases, comparing with those with squamous cell carcinoma (42.9% vs 15.8%,
      P = 0.004). Young patients with adenocarcinoma had shorter progression-free
      survival than those who had squamous cell carcinoma (P = 0.024). Patients aged 35
      years or younger with positive postoperative pathological risk factors had
      shorter progression-free survival, comparing with those with negative factors
      (P<0.01). CONCLUSION: Patients over 35 years were preliminarily diagnosed as
      advanced FIGO stage and they were more likely to have deep stromal invasion,
      LVSI, LN metastases, parametrial and surgical margin involvement. Regarding to
      young patients, cervical adenocarcinoma increased the risk of LN metastases and
      positive postoperative pathological risk factors could apparently worsen the
      prognosis. Histological type and LN metastases were independent prognostic
      factors for young patients in southwestern China. We re-emphasize the importance
      of health education and regular smear screening for elder women, and more
      attention should be paid to young patients with adenocarcinoma or LN metastases.

PMID- 24130748
TI  - Individual-to-resource landscape interaction strength can explain different
      collective feeding behaviours.
AB  - Taking in sufficient quantities of nutrients is vital for all living beings and
      in doing so, individuals interact with the local resource environment. Here, we
      focus explicitly on the interactions between feeding individuals and the resource
      landscape. In particular, we are interested in the emergent movement dynamics
      resulting from these interactions. We present an individual-based simulation
      model for the movement of populations in a resource landscape that allows us to
      vary the strength of the interactions mentioned above. The key assumption and
      novelty of our model is that individuals can cause the release of additional
      nutrients, as well as consuming them. Our model produces clear predictions. For
      example, we expect more tortuous individual movement paths and higher levels of
      aggregation in populations occupying homogeneous environments where individual
      movement makes more nutrients available. We also show how observed movement
      dynamics could change when local nutrient sources are depleted or when the
      population density increases. Our predictions are testable and qualitatively
      reproduce the different feeding behaviours observed in filter-feeding ducks, for
      example. We suggest that considering two-way interactions between feeding
      individuals and resource landscapes could help to explain fine-scale movement
      dynamics. 

PMID- 24130750
TI  - Outlook on a worldwide forest transition.
AB  - It is not clear whether a worldwide "forest transition" to net reforestation will
      ever occur, and the need to address the main driver--agriculture--is compelling.
      We present a mathematical model of land use dynamics based on the world food
      equation that explains historical trends in global land use on the millennial
      scale. The model predicts that a global forest transition only occurs under a
      small and very specific range of parameter values (and hence seems unlikely) but
      if it does occur, it would have to occur within the next 70 years. In our
      baseline scenario, global forest cover continues to decline until it stabilizes
      within the next two centuries at 22% of global land cover, and wild pasture at
      1.4%. Under other scenarios the model predicts unanticipated dynamics wherein a
      forest transition may relapse, heralding a second era of deforestation; this
      brings into question national-level forest transitions observed in recent
      decades, and suggests we need to expand our lexicon of possibilities beyond the
      simple "forest transition/no forest transition" dichotomy. This research also
      underscores that the challenge of feeding a growing population while conserving
      natural habitat will likely continue for decades to come.

PMID- 24130749
TI  - Incidence and cost of pneumonia in older adults with COPD in the United States.
AB  - OBJECTIVES: To estimate the incidence of pneumonia by COPD status and the excess
      cost of inpatient primary pneumonia in elders with COPD. STUDY DESIGN: A
      retrospective, longitudinal study using claims linked to eligibility/demographic
      data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through
      2007. METHODS: Incidence rates of pneumonia were calculated for elders with and
      without COPD and for elders with COPD and coexistent congestive heart failure
      (CHF). Propensity-score matching with multivariate generalized linear regression
      was used to estimate the excess direct medical cost of inpatient primary
      pneumonia in elders with COPD as compared with elders with COPD but without a
      pneumonia hospitalization. RESULTS: Elders with COPD had nearly six-times the
      incidence of pneumonia compared with elders without COPD (167.6/1000 person-years
      versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders
      with COPD and CHF compared with elders without COPD. The incidence of inpatient
      primary pneumonia among elders with COPD was 54.2/1000 person-years compared with
      7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to
      11.0 for elders with COPD and CHF compared with elders without COPD. The one-year
      excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697
      ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was
      accrued during the quarter of the index hospitalization. During months 13 through
      24 following the index hospitalization, the excess direct medical cost was $
      5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01). CONCLUSIONS: Pneumonia
      occurs more frequently in elders with COPD than without COPD. The excess direct
      medical cost in elders with inpatient pneumonia extends up to 24 months following
      the index hospitalization and represents $28,638 in 2010 dollars.

PMID- 24130751
TI  - GCN2 in the brain programs PPARgamma2 and triglyceride storage in the liver
      during perinatal development in response to maternal dietary fat.
AB  - The liver plays a central role in regulating lipid metabolism and facilitates
      efficient lipid utilization and storage. We discovered that a modest increase in
      maternal dietary fat in mice programs triglyceride storage in the liver of their
      developing offspring. The activation of this programming is not apparent,
      however, until several months later at the adult stage. We found that the
      perinatal programming of adult hepatic triglyceride storage was controlled by the
      eIF2alpha kinase GCN2 (EIF2AK4) in the brain of the offspring, which stimulates
      epigenetic modification of the Ppargamma2 gene in the neonatal liver. Genetic
      ablation of Gcn2 in the offspring exhibited reduced hepatic triglyceride storage
      and repressed expression of the peroxisome proliferator-activated receptor gamma
      2 (Ppargamma2) and two lipid droplet protein genes, Fsp27 and Cidea. Brain
      specific, but not liver-specific, Gcn2 KO mice exhibit these same defects
      demonstrating that GCN2 in the developing brain programs hepatic triglyceride
      storage. GCN2 and nutrition-dependent programming of Ppargamma2 is correlated
      with trimethylation of lysine 4 of histone 3 (H3K4me3) in the Ppargamma2 promoter
      region during neonatal development. In addition to regulating hepatic
      triglyceride in response to modest changes in dietary fat, Gcn2 deficiency
      profoundly impacts the severity of the obese-diabetic phenotype of the leptin
      receptor mutant (db/db) mouse, by reducing hepatic steatosis and obesity but
      exacerbating the diabetic phenotype. We suggest that GCN2-dependent perinatal
      programming of hepatic triglyceride storage is an adaptation to couple early
      nutrition to anticipated needs for hepatic triglyceride storage in adults.
      However, increasing the hepatic triglyceride set point during perinatal
      development may predispose individuals to hepatosteatosis, while reducing
      circulating fatty acid levels that promote insulin resistance. 

PMID- 24130752
TI  - Risk of chromosomal abnormalities in early spontaneous abortion after assisted
      reproductive technology: a meta-analysis.
AB  - BACKGROUND: Studies on the risk of chromosomal abnormalities in early spontaneous
      abortion after assisted reproductive technology (ART) are relatively
      controversial and insufficient. Thus, to obtain a more precise evaluation of the
      risk of embryonic chromosomal abnormalities in first-trimester miscarriage after
      ART, we performed a meta-analysis of all available case-control studies relating
      to the cytogenetic analysis of chromosomal abnormalities in first-trimester
      miscarriage after ART. METHODS: Literature search in the electronic databases
      MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL)
      based on the established strategy. Meta-regression, subgroup analysis, and
      Galbraith plots were conducted to explore the sources of heterogeneity. RESULTS:
      A total of 15 studies with 1,896 cases and 1,186 controls relevant to the risk of
      chromosomal abnormalities in first- trimester miscarriage after ART, and 8
      studies with 601 cases and 602 controls evaluating frequency of chromosome
      anomaly for maternal age>=35 versus <35 were eligible for the meta-analysis. No
      statistical difference was found in risk of chromosomally abnormal miscarriage
      compared to natural conception and the different types of ART utilized, whereas
      the risk of fetal aneuploidy significantly increased with maternal age>=35 (OR
      2.88, 95% CI: 1.74-4.77). CONCLUSIONS: ART treatment does not present an
      increased risk for chromosomal abnormalities occurring in a first trimester
      miscarriage, but incidence of fetal aneuploidy could increase significantly with
      advancing maternal age.

PMID- 24130753
TI  - Chronic academic stress increases a group of microRNAs in peripheral blood.
AB  - MicroRNAs (miRNAs) play key roles in regulation of cellular processes in response
      to changes in environment. In this study, we examined alterations in miRNA
      profiles in peripheral blood from 25 male medical students two months and two
      days before the National Examination for Medical Practitioners. Blood obtained
      one month after the examination were used as baseline controls. Levels of seven
      miRNAs (miR-16, -20b, -26b, -29a, -126, -144 and -144*) were significantly
      elevated during the pre-examination period in association with significant down
      regulation of their target mRNAs (WNT4, CCM2, MAK, and FGFR1 mRNAs) two days
      before the examination. State anxiety assessed two months before the examination
      was positively and negatively correlated with miR-16 and its target WNT4 mRNA
      levels, respectively. Fold changes in miR-16 levels from two days before to one
      month after the examination were inversely correlated with those in WNT4 mRNA
      levels over the same time points. We also confirmed the interaction between miR
      16 and WNT4 3'UTR in HEK293T cells overexpressing FLAG-tagged WNT4 3'UTR and miR
      16. Thus, a distinct group of miRNAs in periheral blood may participate in the
      integrated response to chronic academic stress in healthy young men. 

PMID- 24130754
TI  - Pathological cyclic strain-induced apoptosis in human periodontal ligament cells
      through the RhoGDIalpha/caspase-3/PARP pathway.
AB  - AIM: Human periodontal ligament (PDL) cells incur changes in morphology and
      express proteins in response to cyclic strain. However, it is not clear whether
      cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and
      if so, what mechanism(s) are responsible. The aim of the present study was to
      elucidate the molecular mechanisms by which pathological levels of cyclic strain
      induce human PDL cell apoptosis. MATERIALS AND METHODS: Human PDL cells were
      obtained from healthy premolar tissue. After three to five passages in culture,
      the cells were subjected to 20% cyclic strain at a frequency of 0.1 Hz for 6 or
      24 h using an FX-5000T system. Morphological changes of the cells were assessed
      by inverted phase-contrast microscopy, and apoptosis was detected by fluorescein
      isothiocyanate (FITC)-conjugated annexin V and propidium iodide staining followed
      by flow cytometry. Protein expression was evaluated by Western blot analysis.
      RESULTS: The number of apoptotic human PDL cells increased in a time-dependent
      manner in response to pathological cyclic strain. The stretched cells were
      oriented parallel to each another with their long axes perpendicular to the
      strain force vector. Cleaved caspase-3 and poly-ADP-ribose polymerase (PARP)
      protein levels increased in response to pathological cyclic strain over time,
      while Rho GDP dissociation inhibitor alpha (RhoGDIalpha) decreased. Furthermore,
      knock-down of RhoGDIalpha by targeted siRNA transfection increased stretch
      induced apoptosis and upregulated cleaved caspase-3 and PARP protein levels.
      Inhibition of caspase-3 prevented stretch-induced apoptosis, but did not change
      RhoGDIalpha protein levels. CONCLUSION: The overall results suggest that
      pathological-level cyclic strain not only influenced morphology but also induced
      apoptosis in human PDL cells through the RhoGDIalpha/caspase-3/PARP pathway. Our
      findings provide novel insight into the mechanism of apoptosis induced by
      pathological cyclic strain in human PDL cells.

PMID- 24130755
TI  - Comorbid diseases interact with breast cancer to affect mortality in the first
      year after diagnosis--a Danish nationwide matched cohort study.
AB  - BACKGROUND: Survival of breast cancer patients with comorbidity, compared to
      those without comorbidity, has been well characterized. The interaction between
      comorbid diseases and breast cancer, however, has not been well-studied. METHODS:
      From Danish nationwide medical registries, we identified all breast cancer
      patients between 45 and 85 years of age diagnosed from 1994 to 2008. Women
      without breast cancer were matched to the breast cancer patients on specific
      comorbid diseases included in the Charlson comorbidity Index (CCI). Interaction
      contrasts were calculated as a measure of synergistic effect on mortality between
      comorbidity and breast cancer. RESULTS: The study included 47,904 breast cancer
      patients and 237,938 matched comparison women. In the first year, the strongest
      interaction between comorbidity and breast cancer was observed in breast cancer
      patients with a CCI score of >=4, which accounted for 29 deaths per 1000 person
      years. Among individual comorbidities, dementia interacted strongly with breast
      cancer and accounted for 148 deaths per 1000 person-years within one year of
      follow-up. There was little interaction between comorbidity and breast cancer
      during one to five years of follow-up. CONCLUSIONS: There was substantial
      interaction between comorbid diseases and breast cancer, affecting mortality.
      Successful treatment of the comorbid diseases or the breast cancer can delay
      mortality caused by this interaction in breast cancer patients.

PMID- 24130756
TI  - Efficient and rapid C. elegans transgenesis by bombardment and hygromycin B
      selection.
AB  - We report a simple, cost-effective, scalable and efficient method for creating
      transgenic Caenorhabditis elegans that requires minimal hands-on time. The method
      combines biolistic bombardment with selection for transgenics that bear a
      hygromycin B resistance gene on agar plates supplemented with hygromycin B,
      taking advantage of our observation that hygromycin B is sufficient to kill wild
      type C. elegans at very low concentrations. Crucially, the method provides
      substantial improvements in the success of bombardments for isolating
      transmitting strains, the isolation of multiple independent strains, and the
      isolation of integrated strains: 100% of bombardments in a large data set yielded
      transgenics; 10 or more independent strains were isolated from 84% of
      bombardments, and up to 28 independent strains were isolated from a single
      bombardment; 82% of bombardments yielded stably transmitting integrated lines
      with most yielding multiple integrated lines. We anticipate that the selection
      will be widely adopted for C. elegans transgenesis via bombardment, and that
      hygromycin B resistance will be adopted as a marker in other approaches for
      manipulating, introducing or deleting DNA in C. elegans. 

PMID- 24130757
TI  - Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
AB  - TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins,
      containing a modular central domain that recognizes specific DNA sequences.
      Recently, the crystallographic studies of TALEs revealed the structure of DNA
      recognition domain. In this article, molecular dynamics (MD) simulations are
      employed to study two crystal structures of an 11.5-repeat TALE, in the presence
      and absence of DNA, respectively. The simulated results indicate that the
      specific binding of RVDs (repeat-variable diresidues) with DNA leads to the
      markedly reduced fluctuations of tandem repeats, especially at the two ends. In
      the DNA-bound TALE system, the base-specific interaction is formed mainly by the
      residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are
      unfavorable for the TALE-DNA binding. These observations are consistent with
      experimental studies. By using principal component analysis (PCA), the dominant
      motions are open-close movements between the two ends of the superhelical
      structure in both DNA-free and DNA-bound TALE systems. The open-close movements
      are found to be critical for the recognition and binding of TALE-DNA based on the
      analysis of free energy landscape (FEL). The conformational analysis of DNA
      indicates that the 5' end of DNA target sequence has more remarkable structural
      deformability than the other sites. Meanwhile, the conformational change of DNA
      is likely associated with the specific interaction of TALE-DNA. We further
      suggest that the arrangement of N-terminal repeats with strong RVDs may help in
      the design of efficient TALEs. This study provides some new insights into the
      understanding of the TALE-DNA recognition mechanism. 

PMID- 24130758
TI  - The incidence and survival rate of population-based pancreatic cancer patients:
      Shanghai Cancer Registry 2004-2009.
AB  - BACKGROUND: Pancreatic cancer is a devastating disease with dismal prognosis.
      Large population-based evidence on its survival rate and influence factors is
      lacking in China. OBJECTIVE: This study aimed to depict the demographic factors,
      tumor characteristics, incidence rate and survival rate of pancreatic cancer
      cases in urban China. METHODS: The demographic factors, tumor characteristics
      were collected for all the pancreatic cancer cases identified during 2004 to 2009
      from the Shanghai Cancer Registry. The survival time was ascertained through
      linkage of the Shanghai Cancer Registry and the Shanghai Vital Statistics
      Registry. The deadline of death certificates was the end of December 2012. Kaplan
      Meier method and Cox proportional-hazards regression model were used to explore
      the survival rate and influence factors. RESULTS: 11,672 new pancreatic cancer
      cases were identified among Shanghai residency during 2004 to 2009. The crude
      incidence rate of pancreatic cancer was increasing from 12.80/100,000 in 2004 to
      15.66/100,000 in 2009, while the standardized incidence rate was about
      6.70/100,000 and didn't change a lot. The overall 5-year survival rate was 4.1%
      and the median survival time was 3.9 (95% Confidence Interval (CI) 3.8-4.0)
      months. Subjects had received surgical resection had improved survival (HR  =
      0.742, 95% CI: 0.634-0.868) than its counterparts. In adjusted multivariable Cox
      proportional-hazard models, factors associated with poor survival included older
      age at diagnosis (age > = 70 years: hazard ratio (HR)  = 1.827, 95% CI: 1.614
      2.067), male sex (HR  = 1.155, 95% CI: 1.041-1.281), distant disease at diagnosis
      (HR =  1.257, 95% CI: 1.061-1.488), positive lymph node (HR  = 1.236, 95% CI:
      1.085-1.408), tumor stage (Stage IV HR  = 2.817, 95% CI: 2.029-3.909).
      CONCLUSION: The age-adjusted incidence rate was stable and overall survival rate
      was low among pancreatic cancer patients of Shanghai residency. Early detection
      and improved treatment strategies are needed to improve prognosis for this deadly
      disease.

PMID- 24130759
TI  - Spatial, temporal, and habitat-related variation in abundance of pelagic fishes
      in the Gulf of Mexico: potential implications of the deepwater horizon oil spill.
AB  - Time-series data collected over a four-year period were used to characterize
      patterns of abundance for pelagic fishes in the northern Gulf of Mexico (GoM)
      before (2007-2009) and after (2010) the Deepwater Horizon oil spill. Four
      numerically dominant pelagic species (blackfin tuna, blue marlin, dolphinfish,
      and sailfish) were included in our assessment, and larval density of each species
      was lower in 2010 than any of the three years prior to the oil spill, although
      larval abundance in 2010 was often statistically similar to other years surveyed.
      To assess potential overlap between suitable habitat of pelagic fish larvae and
      surface oil, generalized additive models (GAMs) were developed to evaluate the
      influence of ocean conditions on the abundance of larvae from 2007-2009.
      Explanatory variables from GAMs were then linked to environmental data from 2010
      to predict the probability of occurrence for each species. The spatial extent of
      surface oil overlapped with early life habitat of each species, possibly
      indicating that the availability of high quality habitat was affected by the DH
      oil spill. Shifts in the distribution of spawning adults is another factor known
      to influence the abundance of larvae, and the spatial occurrence of a model
      pelagic predator (blue marlin) was characterized over the same four-year period
      using electronic tags. The spatial extent of oil coincided with areas used by
      adult blue marlin from 2007-2009, and the occurrence of blue marlin in areas
      impacted by the DH oil spill was lower in 2010 relative to pre-spill years. 

PMID- 24130760
TI  - Association of proteinuria threshold in pre-eclampsia with maternal and perinatal
      outcomes: a nested case control cohort of high risk women.
AB  - OBJECTIVES: To evaluate occurrence of adverse maternal and perinatal outcomes
      with different thresholds of proteinuria (300-499 mg and >=500 mg/24 hours) in
      pre-eclamptic women, comparing outcomes against women with chronic and
      gestational hypertension. DESIGN: Secondary analysis of the Vitamins in Pre
      Eclampsia Trial. SETTING: 25 UK hospitals in ten geographical areas. POPULATION:
      946 women with pre-existing risk factors for pre-eclampsia. METHODS: Women with
      pre-eclampsia and proteinuria 300-499 mg/24 h (PE300, referent group, n=60) or
      proteinuria >=500 mg/24 h (PE500, n=161) were compared with two groups of non
      proteinuric women with chronic hypertension (CHT, n=615) or gestational
      hypertension (GH, n=110). MAIN OUTCOME MEASURES: MATERNAL: progression to severe
      hypertension. Perinatal: small for gestational age (SGA) <5(th) centile,
      gestation at delivery. RESULTS: Severe hypertension occurred more frequently in
      PE500 (35%) and PE300 (27%) than CHT (5.9%; P<=0.01) and GH (10%; p<=0.001).
      Gestation at delivery was earlier in PE500 (33.2 w) than PE300 (37.3 w;
      P<=0.001), and later in CHT (38.3 w; P<=0.05) and GH (39.1 w; P<=0.001). SGA
      infants were more frequent in PE300 (32%) than in CHT (13.3%; P<=0.001) and GH
      (16.5%; P<=0.05). Women in PE500 were more likely to have a caesarean section
      than PE300 (78% vs. 48%; P<=0.001), and to receive magnesium sulphate (17% vs.
      1.7%, P<=0.05). CONCLUSION: Women with PE300 have complication rates above those
      of women managed as out-patients (GH and CHT), meriting closer surveillance and
      confirming 300 mg/d as an appropriate threshold for determining in-patient
      management. Adverse perinatal outcomes are higher still in women with PE500.

PMID- 24130761
TI  - Timing and tuning for familiarity of cortical responses to faces.
AB  - Different kinds of known faces activate brain areas to dissimilar degrees.
      However, the tuning to type of knowledge, and the temporal course of activation,
      of each area have not been well characterized. Here we measured, with functional
      magnetic resonance imaging, brain activity elicited by unfamiliar, visually
      familiar, and personally-familiar faces. We assessed response amplitude and
      duration using flexible hemodynamic response functions, as well as the tuning to
      face type, of regions within the face processing system. Core face processing
      areas (occipital and fusiform face areas) responded to all types of faces with
      only small differences in amplitude and duration. In contrast, most areas of the
      extended face processing system (medial orbito-frontal, anterior and posterior
      cingulate) had weak responses to unfamiliar and visually-familiar faces, but were
      highly tuned and exhibited prolonged responses to personally-familiar faces. This
      indicates that the neural processing of different types of familiar faces not
      only differs in degree, but is probably mediated by qualitatively distinct
      mechanisms. 

PMID- 24130762
TI  - An improved SELEX-Seq strategy for characterizing DNA-binding specificity of
      transcription factor: NF-kappaB as an example.
AB  - SELEX-Seq is now the optimal high-throughput technique for characterizing DNA
      binding specificities of transcription factors. In this study, we introduced an
      improved EMSA-based SELEX-Seq strategy with several advantages. The improvements
      of this strategy included: (1) using a FAM-labeled probe to track protein-DNA
      complex in polyacrylamide gel for rapidly recovering the protein-bound dsDNA
      without relying on traditional radioactive labeling or ethidium bromide staining;
      (2) monitoring the specificity of SELEX selection by detecting a positive and
      negative sequence doped into the input DNAs used in each round with PCR
      amplification; (3) using nested PCR to ensure the specificity of PCR
      amplification of the selected DNAs after each round; (4) using the nucleotides
      added at the 5' end of the nested PCR primers as the split barcode to code DNAs
      from various rounds for multiplexing sequencing samples. The split barcode
      minimized selection times and thus greatly simplified the current SELEX-Seq
      procedure. The reliability of the strategy was demonstrated by performing a
      successful SELEX-Seq of a well-known transcription factor, NF-kappaB. Therefore,
      this study provided a useful SELEX-Seq strategy for characterizing DNA-binding
      specificities of transcription factors. 

PMID- 24130763
TI  - Inflammation and oxidative stress are elevated in the brain, blood, and adrenal
      glands during the progression of post-traumatic stress disorder in a predator
      exposure animal model.
AB  - This study sought to analyze specific pathophysiological mechanisms involved in
      the progression of post-traumatic stress disorder (PTSD) by utilizing an animal
      model. To examine PTSD pathophysiology, we measured damaging reactive oxygen
      species and inflammatory cytokines to determine if oxidative stress and
      inflammation in the brain, adrenal glands, and systemic circulation were
      upregulated in response to constant stress. Pre-clinical PTSD was induced in
      naive, male Sprague-Dawley rats via a predator exposure/psychosocial stress
      regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage
      with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition,
      PTSD group rats were subjected to psychosocial stress whereby their cage cohort
      was changed daily. This model has been shown to cause heightened anxiety,
      exaggerated startle response, impaired cognition, and increased cardiovascular
      reactivity, all of which are common symptoms seen in humans with PTSD. At the
      conclusion of the predator exposure/psychosocial stress regimen, the rats were
      euthanized and their brains were dissected to remove the hippocampus, amygdala,
      and pre-frontal cortex (PFC), the three areas commonly associated with PTSD
      development. The adrenal glands and whole blood were also collected to assess
      systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain
      regions revealed oxidative stress increased during PTSD progression. In addition,
      examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated
      neurological inflammatory molecules were significantly upregulated in the PTSD
      group vs. controls. These results indicate oxidative stress and inflammation in
      the brain, adrenal glands, and systemic circulation may play a critical role in
      the development and further exacerbation of PTSD. Thus, PTSD may not be solely a
      neurological pathology but may progress as a systemic condition involving
      multiple organ systems. 

PMID- 24130764
TI  - The land Gini coefficient and its application for land use structure analysis in
      China.
AB  - We introduce the Gini coefficient to assess the rationality of land use
      structure. The rapid transformation of land use in China provides a typical case
      for land use structure analysis. In this study, a land Gini coefficient (LGC)
      analysis tool was developed. The land use structure rationality was analyzed and
      evaluated based on statistical data for China between 1996 and 2008. The results
      show: (1)The LGC of three major land use types-farmland, built-up land and unused
      land-was smaller when the four economic districts were considered as assessment
      units instead of the provinces. Therefore, the LGC is spatially dependent; if the
      calculation unit expands, then the LGC decreases, and this relationship does not
      change with time. Additionally, land use activities in different provinces of a
      single district differed greatly. (2) At the national level, the LGC of the three
      main land use types indicated that during the 13 years analyzed, the farmland and
      unused land were evenly distributed across China. However, the built-up land
      distribution was relatively or absolutely unequal and highlights the rapid
      urbanization in China. (3) Trends in the distribution of the three major land use
      types are very different. At the national level, when using a district as the
      calculation unit, the LGC of the three main land use types increased, and their
      distribution became increasingly concentrated. However, when a province was used
      as the calculation unit, the LGC of the farmland increased, while the LGC of the
      built-up and unused land decreased. These findings indicate that the distribution
      of the farmland became increasingly concentrated, while the built-up land and
      unused land became increasingly uniform. (4) The LGC analysis method of land use
      structure based on geographic information systems (GIS) is flexible and
      convenient. 

PMID- 24130765
TI  - Exercise training reverses skeletal muscle atrophy in an experimental model of
      VCP disease.
AB  - BACKGROUND: The therapeutic effects of exercise resistance and endurance training
      in the alleviation of muscle hypertrophy/atrophy should be considered in the
      management of patients with advanced neuromuscular diseases. Patients with
      progressive neuromuscular diseases often experience muscle weakness, which
      negatively impact independence and quality of life levels. Mutations in the
      valosin containing protein (VCP) gene lead to Inclusion body myopathy associated
      with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more
      recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases.
      METHODS/PRINCIPLE FINDINGS: The present investigation was undertaken to examine
      the effects of uphill and downhill exercise training on muscle histopathology and
      the autophagy cascade in an experimental VCP mouse model carrying the R155H
      mutation. Progressive uphill exercise in VCP(R155H/+) mice revealed significant
      improvement in muscle strength and performance by grip strength and Rotarod
      analyses when compared to the sedentary mice. In contrast, mice exercised to run
      downhill did not show any significant improvement. Histologically, the uphill
      exercised VCP(R155H/+) mice displayed an improvement in muscle atrophy, and
      decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43
      autophagy markers, suggesting an alleviation of disease-induced myopathy
      phenotypes. There was also an improvement in the Paget-like phenotype.
      CONCLUSIONS: Collectively, our data highlights that uphill exercise training in
      VCP(R155H/+) mice did not have any detrimental value to the function of muscle,
      and may offer effective therapeutic options for patients with VCP-associated
      diseases.

PMID- 24130766
TI  - A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric
      modulator of FFAR1.
AB  - Selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist fasiglifam (TAK-875),
      an antidiabetic drug under phase 3 development, potentiates insulin secretion in
      a glucose-dependent manner by activating FFAR1 expressed in pancreatic beta
      cells. Although fasiglifam significantly improved glycemic control in type 2
      diabetes patients with a minimum risk of hypoglycemia in a phase 2 study, the
      precise mechanisms of its potent pharmacological effects are not fully
      understood. Here we demonstrate that fasiglifam acts as an ago-allosteric
      modulator with a partial agonistic activity for FFAR1. In both Ca(2+) influx and
      insulin secretion assays using cell lines and mouse islets, fasiglifam showed
      positive cooperativity with the FFAR1 ligand gamma-linolenic acid (gamma-LA).
      Augmentation of glucose-induced insulin secretion by fasiglifam, gamma-LA, or
      their combination was completely abolished in pancreatic islets of FFAR1-knockout
      mice. In diabetic rats, the insulinotropic effect of fasiglifam was suppressed by
      pharmacological reduction of plasma free fatty acid (FFA) levels using a
      lipolysis inhibitor, suggesting that fasiglifam potentiates insulin release in
      conjunction with plasma FFAs in vivo. Point mutations of FFAR1 differentially
      affected Ca(2+) influx activities of fasiglifam and gamma-LA, further indicating
      that these agonists may bind to distinct binding sites. Our results strongly
      suggest that fasiglifam is an ago-allosteric modulator of FFAR1 that exerts its
      effects by acting cooperatively with endogenous plasma FFAs in human patients as
      well as diabetic animals. These findings contribute to our understanding of
      fasiglifam as an attractive antidiabetic drug with a novel mechanism of action. 

PMID- 24130767
TI  - Different responses to reward comparisons by three primate species.
AB  - BACKGROUND: Recently, much attention has been paid to the role of cooperative
      breeding in the evolution of behavior. In many measures, cooperative breeders are
      more prosocial than non-cooperatively breeding species, including being more
      likely to actively share food. This is hypothesized to be due to selective
      pressures specific to the interdependency characteristic of cooperatively
      breeding species. Given the high costs of finding a new mate, it has been
      proposed that cooperative breeders, unlike primates that cooperate in other
      contexts, should not respond negatively to unequal outcomes between themselves
      and their partner. However, in this context such pressures may extend beyond
      cooperative breeders to other species with pair-bonding and bi-parental care.
      METHODS: Here we test the response of two New World primate species with
      different parental strategies to unequal outcomes in both individual and social
      contrast conditions. One species tested was a cooperative breeder (Callithrix
      spp.) and the second practiced bi-parental care (Aotus spp.). Additionally, to
      verify our procedure, we tested a third confamilial species that shows no such
      interdependence but does respond to individual (but not social) contrast (Saimiri
      spp.). We tested all three genera using an established inequity paradigm in which
      individuals in a pair took turns to gain rewards that sometimes differed from
      those of their partners. CONCLUSIONS: None of the three species tested responded
      negatively to inequitable outcomes in this experimental context. Importantly, the
      Saimiri spp responded to individual contrast, as in earlier studies, validating
      our procedure. When these data are considered in relation to previous studies
      investigating responses to inequity in primates, they indicate that one aspect of
      cooperative breeding, pair-bonding or bi-parental care, may influence the
      evolution of these behaviors. These results emphasize the need to study a variety
      of species to gain insight in to how decision-making may vary across social
      structures.

PMID- 24130768
TI  - What happens during the stimulus onset asynchrony in the dot-probe task?
      Exploring the role of eye movements in the assessment of attentional biases.
AB  - The dot-probe paradigm is one of the most often used paradigms to investigate
      attentional biases towards emotional information. However, a large number of the
      dot-probe studies so far used a long stimulus onset asynchrony allowing for eye
      movements to occur, which might increase the error variance. This study aimed at
      addressing this methodological issue by varying the instructions with regard to
      the gaze behavior and calculating the reaction time (RT) bias score (i.e., RTs
      for targets presented at the location of the emotional compared to the neutral
      stimulus) separately for trials with eye movements and trials without eye
      movements. Results of Experiment 1 (using typical instructions, i.e.,
      instructions that are lenient with regard to eye movements) showed an RT bias,
      but only in the trials without eye movements The overall RT bias (calculated
      "blind" for eye movements) was non-significant. In Experiment 2, stricter
      instructions and small changes in the procedure led to a sharp decrease in the
      number of eye movements, such that both the RT bias in the trials without eye
      movements as well as the RT bias across all trials was significant. 

PMID- 24130769
TI  - Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, enhances
      radiosensitivity and suppresses lung metastasis in breast cancer in vitro and in
      vivo.
AB  - Triple-negative breast cancer (TNBC), defined by the absence of an estrogen
      receptor, progesterone receptor, and human epidermal growth factor receptor 2
      expression, is associated with an early recurrence of disease and poor outcome.
      Furthermore, the majority of deaths in breast cancer patients are from metastases
      instead of from primary tumors. In this study, MCF-7 (an estrogen receptor
      positive human breast cancer cell line), MDA-MB-231 (a human TNBC cell line) and
      4T1 (a mouse TNBC cell line) were used to investigate the anti-cancer effects of
      ionizing radiation (IR) combined with suberoylanilide hydroxamic acid (SAHA, an
      inhibitor of histone deacetylase (HDAC)) and to determine the underlying
      mechanisms of these effects in vitro and in vivo. We also evaluated the ability
      of SAHA to inhibit the metastasis of 4T1 cells. We found that IR combined with
      SAHA showed increased therapeutic efficacy when compared with either treatment
      alone in MCF-7, MDA-MB-231 and 4T1 cells. Moreover, the combined treatment
      enhanced DNA damage through the inhibition of DNA repair proteins. The combined
      treatment was induced primarily through autophagy and ER stress. In an orthotopic
      breast cancer mouse model, the combination treatment showed a greater inhibition
      of tumor growth. In addition, SAHA inhibited the migration and invasion abilities
      of 4T1 cells and inhibited breast cancer cell migration by inhibiting the
      activity of MMP-9. In an in vivo experimental metastasis mouse model, SAHA
      significantly inhibited lung metastasis. SAHA not only enhances radiosensitivity
      but also suppresses lung metastasis in breast cancer. These novel findings
      suggest that SAHA alone or combined with IR could serve as a potential
      therapeutic strategy for breast cancer. 

PMID- 24130770
TI  - Heritabilities of directional asymmetry in the fore- and hindlimbs of rabbit
      fetuses.
AB  - Directional asymmetry (DA), where at the population level symmetry differs from
      zero, has been reported in a wide range of traits and taxa, even for traits in
      which symmetry is expected to be the target of selection such as limbs or wings.
      In invertebrates, DA has been suggested to be non-adaptive. In vertebrates, there
      has been a wealth of research linking morphological asymmetry to behavioural
      lateralisation. On the other hand, the prenatal expression of DA and evidences
      for quantitative genetic variation for asymmetry may suggest it is not solely
      induced by differences in mechanic loading between sides. We estimate
      quantitative genetic variation of fetal limb asymmetry in a large dataset of
      rabbits. Our results showed a low but highly significant level of DA that is
      partially under genetic control for all traits, with forelimbs displaying higher
      levels of asymmetry. Genetic correlations were positive within limbs, but
      negative across bones of fore and hind limbs. Environmental correlations were
      positive for all, but smaller across fore and hind limbs. We discuss our results
      in light of the existence and maintenance of DA in locomotory traits. 

PMID- 24130771
TI  - Targeted exome sequencing integrated with clinicopathological information reveals
      novel and rare mutations in atypical, suspected and unknown cases of Alport
      syndrome or proteinuria.
AB  - We applied customized targeted next-generation exome sequencing (NGS) to
      determine if mutations in genes associated with renal malformations, Alport
      syndrome (AS) or nephrotic syndrome are a potential cause of renal abnormalities
      in patients with equivocal or atypical presentation. We first sequenced 4,041
      exons representing 292 kidney disease genes in a Caucasian woman with a history
      of congenital vesicoureteral reflux (VUR), recurrent urinary tract infections and
      hydronephrosis who presented with nephrotic range proteinuria at the age of 45.
      Her biopsy was remarkable for focal segmental glomerulosclerosis (FSGS), a
      potential complication of longstanding VUR. She had no family history of renal
      disease. Her proteinuria improved initially, however, several years later she
      presented with worsening proteinuria and microhematuria. NGS analysis revealed
      two deleterious COL4A3 mutations, one novel and the other previously reported in
      AS, and a novel deleterious SALL2 mutation, a gene linked to renal malformations.
      Pedigree analysis confirmed that COL4A3 mutations were nonallelic and compound
      heterozygous. The genomic results in conjunction with subsequent abnormal
      electron microscopy, Collagen IV minor chain immunohistochemistry and progressive
      sensorineural hearing loss confirmed AS. We then modified our NGS approach to
      enable more efficient discovery of variants associated with AS or a subset of
      FSGS by multiplexing targeted exome sequencing of 19 genes associated with AS or
      FSGS in 14 patients. Using this approach, we found novel or known COL4A3 or
      COL4A5 mutations in a subset of patients with clinically diagnosed or suspected
      AS, APOL1 variants associated with FSGS in African Americans and novel mutations
      in genes associated with nephrotic syndrome. These studies demonstrate the
      successful application of targeted capture-based exome sequencing to
      simultaneously evaluate genetic variations in many genes in patients with complex
      renal phenotypes and provide insights into etiology of conditions with equivocal
      clinical and pathologic presentations. 

PMID- 24130772
TI  - Geographical range and local abundance of tree species in China.
AB  - Most studies on the geographical distribution of species have utilized a few well
      known taxa in Europe and North America, with little research in China and its
      wide range of climate and forest types. We assembled large datasets to quantify
      the geographic ranges of tree species in China and to test several biogeographic
      hypotheses: 1) whether locally abundant species tend to be geographically
      widespread; 2) whether species are more abundant towards their range-centers; and
      3) how abundances are correlated between sites. Local abundances of 651 species
      were derived from four tree plots of 20-25 ha where all individuals >=1 cm in
      stem diameter were mapped and identified taxonomically. Range sizes of these
      species across China were then estimated from over 460,000 geo-referenced
      records; a Bayesian approach was used, allowing careful measures of error of each
      range estimate. The log-transformed range sizes had a bell-shaped distribution
      with a median of 703,000 km(2), and >90% of 651 species had ranges >10(5) km(2).
      There was no relationship between local abundance and range size, and no evidence
      for species being more abundant towards their range-centers. Finally, species'
      abundances were positively correlated between sites. The widespread nature of
      most tree species in China suggests few are vulnerable to global extinction, and
      there is no indication of the double-peril that would result if rare species also
      had narrow ranges. 

PMID- 24130773
TI  - Inheritable and precise large genomic deletions of non-coding RNA genes in
      zebrafish using TALENs.
AB  - Transcription activator-like effector nucleases (TALENs) have so far been applied
      to disrupt protein-coding genes which constitute only 2-3% of the genome in
      animals. The majority (70-90%) of the animal genome is actually transcribed as
      non-coding RNAs (ncRNAs), yet the lack of efficient tools to knockout ncRNA genes
      hinders studies on their in vivo functions. Here we have developed novel
      strategies using TALENs to achieve precise and inheritable large genomic
      deletions and knockout of ncRNA genes in zebrafish. We have demonstrated that
      individual miRNA genes could be disrupted using one pair of TALENs, whereas large
      microRNA (miRNA) gene clusters and long non-coding RNA (lncRNA) genes could be
      precisely deleted using two pairs of TALENs. We have generated large genomic
      deletions of two miRNA clusters (the 1.2 kb miR-17-92 cluster and the 79.8 kb miR
      430 cluster) and one long non-coding RNA (lncRNA) gene (the 9.0 kb malat1), and
      the deletions are transmitted through the germline. Taken together, our results
      establish TALENs as a robust tool to engineer large genomic deletions and
      knockout of ncRNA genes, thus opening up new avenues in the application of TALENs
      to study the genome in vivo. 

PMID- 24130774
TI  - Nitrosylated hemoglobin levels in human venous erythrocytes correlate with
      vascular endothelial function measured by digital reactive hyperemia.
AB  - Impaired nitric oxide (NO)-dependent endothelial function is associated with the
      development of cardiovascular diseases. We hypothesized that erythrocyte levels
      of nitrosylated hemoglobin (HbNO-heme) may reflect vascular endothelial function
      in vivo. We developed a modified subtraction method using Electron Paramagnetic
      Resonance (EPR) spectroscopy to identify the 5-coordinate alpha-HbNO (HbNO)
      concentration in human erythrocytes and examined its correlation with endothelial
      function assessed by peripheral arterial tonometry (PAT). Changes in digital
      pulse amplitude were measured by PAT during reactive hyperemia following brachial
      arterial occlusion in a group of healthy volunteers (50 subjects). Erythrocyte
      HbNO levels were measured at baseline and at the peak of hyperemia. We digitally
      subtracted an individual model EPR signal of erythrocyte free radicals from the
      whole EPR spectrum to unmask and quantitate the HbNO EPR signals. RESULTS: Mean
      erythrocyte HbNO concentration at baseline was 219+/-12 nmol/L (n = 50). HbNO
      levels and reactive hyperemia (RH) indexes were higher in female (free of
      contraceptive pills) than male subjects. We observed a dynamic increase of HbNO
      levels in erythrocytes isolated at 1-2 min of post-occlusion hyperemia (120+/-8%
      of basal levels); post-occlusion HbNO levels were correlated with basal levels.
      Both basal and post-occlusion HbNO levels were significantly correlated with
      reactive hyperemia (RH) indexes (r = 0.58; P<0.0001 for basal HbNO). CONCLUSION:
      The study demonstrates quantitative measurements of 5-coordinate alpha-HbNO in
      human venous erythrocytes, its dynamic physiologic regulation and correlation
      with endothelial function measured by tonometry during hyperemia. This opens the
      way to further understanding of in vivo determinants of NO bioavailability in
      human circulation.

PMID- 24130775
TI  - A SNP based high-density linkage map of Apis cerana reveals a high recombination
      rate similar to Apis mellifera.
AB  - BACKGROUND: The Eastern honey bee, Apis cerana Fabricius, is distributed in
      southern and eastern Asia, from India and China to Korea and Japan and southeast
      to the Moluccas. This species is also widely kept for honey production besides
      Apis mellifera. Apis cerana is also a model organism for studying social
      behavior, caste determination, mating biology, sexual selection, and host
      parasite interactions. Few resources are available for molecular research in this
      species, and a linkage map was never constructed. A linkage map is a prerequisite
      for quantitative trait loci mapping and for analyzing genome structure. We used
      the Chinese honey bee, Apis cerana cerana to construct the first linkage map in
      the Eastern honey bee. RESULTS: F2 workers (N = 103) were genotyped for 126,990
      single nucleotide polymorphisms (SNPs). After filtering low quality and those not
      passing the Mendel test, we obtained 3,000 SNPs, 1,535 of these were informative
      and used to construct a linkage map. The preliminary map contains 19 linkage
      groups, we then mapped the 19 linkage groups to 16 chromosomes by comparing the
      markers to the genome of A. mellfiera. The final map contains 16 linkage groups
      with a total of 1,535 markers. The total genetic distance is 3,942.7 centimorgans
      (cM) with the largest linkage group (180 loci) measuring 574.5 cM. Average marker
      interval for all markers across the 16 linkage groups is 2.6 cM. CONCLUSION: We
      constructed a high density linkage map for A. c. cerana with 1,535 markers.
      Because the map is based on SNP markers, it will enable easier and faster
      genotyping assays than randomly amplified polymorphic DNA or microsatellite based
      maps used in A. mellifera.

PMID- 24130776
TI  - Generation of interleukin-2 receptor gamma gene knockout pigs from somatic cells
      genetically modified by zinc finger nuclease-encoding mRNA.
AB  - Zinc finger nuclease (ZFN) is a powerful tool for genome editing. ZFN-encoding
      plasmid DNA expression systems have been recently employed for the generation of
      gene knockout (KO) pigs, although one major limitation of this technology is the
      use of potentially harmful genome-integrating plasmid DNAs. Here we describe a
      simple, non-integrating strategy for generating KO pigs using ZFN-encoding mRNA.
      The interleukin-2 receptor gamma (IL2RG) gene was knocked out in porcine fetal
      fibroblasts using ZFN-encoding mRNAs, and IL2RG KO pigs were subsequently
      generated using these KO cells through somatic cell nuclear transfer (SCNT). The
      resulting IL2RG KO pigs completely lacked a thymus and were deficient in T and NK
      cells, similar to human X-linked SCID patients. Our findings demonstrate that the
      combination of ZFN-encoding mRNAs and SCNT provides a simple robust method for
      producing KO pigs without genomic integration. 

PMID- 24130777
TI  - Hypoxia integration in the serological proteome analysis unmasks tumor antigens
      and fosters the identification of anti-phospho-eEF2 antibodies as potential
      cancer biomarkers.
AB  - The expression by tumor cells of proteins with aberrant structure, expression or
      distribution accounts for the development of a humoral immune response.
      Autoantibodies (aAb) directed against tumor-associated antigens (TAA) may thus be
      particularly relevant for early detection of cancer. Serological proteome
      analysis (SERPA) aims to identify such circulating aAb through the immunoblotting
      of 2D-separated tumor cell proteins with cancer patient serum and the consecutive
      MS identification of proteins in reactive spots. This method has the advantage to
      use post-translationally modified proteins as a source of potential TAA. Here, we
      applied this strategy by using colorectal tumor cells pre-exposed to hypoxia in
      order to promote the expression of a pattern of TAA more likely to represent in
      vivo conditions. We used two human HCT116 and HT29 colorectal cancer cell lines
      exposed for 48 hours to 1% O2. Spots positive after immunoblotting of 2D
      separated lysates of hypoxic cells with the sera of tumor-bearing mice, were
      collected and analysed by MS for protein identification. Among the hypoxia
      specific immunogenic proteins, we identified a phosphorylated form of eukaryotic
      translation elongation factor 2 (phospho-Thr56 eEF2). We confirmed the increased
      phosphorylation of this protein in hypoxic colorectal tumor cells as well as in
      mouse tumors. Using a specific immunoassay, we could detect the presence of
      corresponding anti-phospho-Thr56 eEF2 aAb in the serum of tumor-bearing mice (vs
      healthy mice). We further documented that the detection of these aAb preceded the
      detection of a palpable tumor mass in mice and validated the presence of anti
      phospho-Thr56 eEF2 aAb in the serum of patients with adenomatous polyps and
      colorectal carcinoma. In conclusion, this study validates a phosphorylated form
      of eEF2 as a new TAA and more generally, provides evidence that integrating
      hypoxia upstream of SERPA offers a more relevant repertoire of TAA able to unmask
      the presence of circulating aAb. 

PMID- 24130778
TI  - IGF-IR promotes prostate cancer growth by stabilizing alpha5beta1 integrin
      protein levels.
AB  - Dynamic crosstalk between growth factor receptors, cell adhesion molecules and
      extracellular matrix is essential for cancer cell migration and invasion.
      Integrins are transmembrane receptors that bind extracellular matrix proteins and
      enable cell adhesion and cytoskeletal organization. They also mediate signal
      transduction to regulate cell proliferation and survival. The type 1 insulin-like
      growth factor receptor (IGF-IR) mediates tumor cell growth, adhesion and
      inhibition of apoptosis in several types of cancer. We have previously
      demonstrated that beta1 integrins regulate anchorage-independent growth of
      prostate cancer (PrCa) cells by regulating IGF-IR expression and androgen
      receptor-mediated transcriptional functions. Furthermore, we have recently
      reported that IGF-IR regulates the expression of beta1 integrins in PrCa cells.
      We have dissected the mechanism through which IGF-IR regulates beta1 integrin
      expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth
      and that beta1 integrins contribute to the regulation of proliferation by IGF-IR.
      We demonstrate that beta1 integrin regulation by IGF-IR does not occur at the
      mRNA level. Exogenous expression of a CD4 - beta1 integrin cytoplasmic domain
      chimera does not interfere with such regulation and fails to stabilize beta1
      integrin expression in the absence of IGF-IR. This appears to be due to the lack
      of interaction between the beta1 cytoplasmic domain and IGF-IR. We demonstrate
      that IGF-IR stabilizes the beta1 subunit by protecting it from proteasomal
      degradation. The alpha5 subunit, one of the binding partners of beta1, is also
      downregulated along with beta1 upon IGF-IR knockdown while no change is observed
      in the expression of the alpha2, alpha3, alpha4, alpha6 and alpha7 subunits. Our
      results reveal a crucial mechanistic role for the alpha5beta1 integrin,
      downstream of IGF-IR, in regulating cancer growth. 

PMID- 24130779
TI  - Amyloid beta(1-40)-induced astrogliosis and the effect of genistein treatment in
      rat: a three-dimensional confocal morphometric and proteomic study.
AB  - Astrocytes are highly involved in regulation and homeostasis of the extracellular
      environment in the healthy brain. In pathological conditions, these cells play a
      major role in the inflammatory response seen in CNS tissues, which is called
      reactive astrogliosis and includes hypertrophy and proliferation of astrocytes.
      Here, we performed 3D confocal microscopy to evaluate the morphological response
      of reactive astrocytes positive for glial fibrillary acidic protein (GFAP) in
      rats, to the presence of Abeta(1-40) in the rat brain before and after treatment
      with genistein. In 50 astrocytes per animal, we measured the volume and surface
      area for the nucleus, cell body, the entire cell, the tissue covered by single
      astrocytes and quantified the number and length of branches, the density of the
      astrocytes and the intensity of GFAP immunoreactivity. Injecting Abeta(1-40) into
      the brain of rats caused astrogliosis indicated by increased values for all
      measured parameters. Mass spectrometric analysis of hippocampal tissue in Abeta(1
      40)-injected brain showed decreased amounts of tubulins, enolases and myelin
      basic protein, and increased amounts of dihydropyrimidinase-related protein 2. In
      Abeta(1-40)-injected rats pretreated with genistein, GFAP intensity was decreased
      to the sham-operated group level, and Abeta(1-40)-induced astrogliosis was
      significantly ameliorated.

PMID- 24130780
TI  - Effects of microRNAs on fucosyltransferase 8 (FUT8) expression in hepatocarcinoma
      cells.
AB  - Fucosyltransferase 8 (FUT8) catalyzes the transfer of alpha1,6-linked fucose to
      the first N-acetylglucosamine in N-linked glycans (core fucosylation). Increased
      core fucosylation has been reported during hepatocarcinogenesis, in both cell
      associated and secreted proteins. Accordingly, increased core fucosylation of
      alpha-fetoprotein and alpha1-antitrypsin is currently used as a diagnostic and
      prognostic indicator. The present study provides new evidences that FUT8 can be
      regulated also through miRNA-mediated mechanisms. Using microRNA/target
      prediction programs, we identified miR-122 and miR-34a seed regions in the 3'
      untranslated region (3'UTR) of FUT8. Then we used human and rodents
      hepatocarcinoma cell lines to evaluate the impact of transfection of miR-122 and
      miR-34a mimics on FUT8 mRNA and protein levels. This study demonstrated that
      forced expression of these miRNAs is able to induce a decrease of FUT8 levels and
      also to affect core fucosylation of secreted proteins. The ability of miR-122 and
      miR-34a to specifically interact with and regulate the 3'UTR of FUT8 was
      demonstrated via a luciferase reporter assay. Since miR-122 and miR-34a
      downregulation is a common feature in spontaneous human hepatocarcinoma, our
      finding that these miRNAs are able to target FUT8 3'UTR suggests that, together
      with transcriptional and other post-transcriptional systems, a miRNA-mediated
      mechanism could also be involved in the increased core fucosylation observed in
      liver tumors. Moreover, these findings also point out that miRNAs may be widely
      involved in the regulation of glycosylation machinery. 

PMID- 24130781
TI  - Use of the robust design to estimate seasonal abundance and demographic
      parameters of a coastal bottlenose dolphin (Tursiops aduncus) population.
AB  - As delphinid populations become increasingly exposed to human activities we rely
      on our capacity to produce accurate abundance estimates upon which to base
      management decisions. This study applied mark-recapture methods following the
      Robust Design to estimate abundance, demographic parameters, and temporary
      emigration rates of an Indo-Pacific bottlenose dolphin (Tursiops aduncus)
      population off Bunbury, Western Australia. Boat-based photo-identification
      surveys were conducted year-round over three consecutive years along pre
      determined transect lines to create a consistent sampling effort throughout the
      study period and area. The best fitting capture-recapture model showed a
      population with a seasonal Markovian temporary emigration with time varying
      survival and capture probabilities. Abundance estimates were seasonally dependent
      with consistently lower numbers obtained during winter and higher during summer
      and autumn across the three-year study period. Specifically, abundance estimates
      for all adults and juveniles (combined) varied from a low of 63 (95% CI 59 to 73)
      in winter of 2007 to a high of 139 (95% CI 134 to148) in autumn of 2009.
      Temporary emigration rates (gamma') for animals absent in the previous period
      ranged from 0.34 to 0.97 (mean  =  0.54; +/-SE 0.11) with a peak during spring.
      Temporary emigration rates for animals present during the previous period
      (gamma'') were lower, ranging from 0.00 to 0.29, with a mean of 0.16 (+/- SE
      0.04). This model yielded a mean apparent survival estimate for juveniles and
      adults (combined) of 0.95 (+/- SE 0.02) and a capture probability from 0.07 to
      0.51 with a mean of 0.30 (+/- SE 0.04). This study demonstrates the importance of
      incorporating temporary emigration to accurately estimate abundance of coastal
      delphinids. Temporary emigration rates were high in this study, despite the large
      area surveyed, indicating the challenges of sampling highly mobile animals which
      range over large spatial areas. 

PMID- 24130782
TI  - Characterization of a new chronic lymphocytic leukemia cell line for mechanistic
      in vitro and in vivo studies relevant to disease.
AB  - Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress,
      however a lack of immortalized cell lines representative of the primary disease
      has hampered a full understanding of disease pathogenesis and development of new
      treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV
      transformation, which displays a similar cytogenetic and immunophenotype observed
      in the patient's CLL (CD5 positive with trisomy 12 and 19). A companion cell line
      was also generated from the same patient (OSU-NB). This cell line lacked typical
      CLL characteristics, and is likely derived from the patient's normal B cells. In
      vitro migration assays demonstrated that OSU-CLL exhibits migratory properties
      similar to primary CLL cells whereas OSU-NB has significantly reduced ability to
      migrate spontaneously or towards chemokine. Microarray analysis demonstrated
      distinct gene expression patterns in the two cell lines, including genes on
      chromosomes 12 and 19, which is consistent with the cytogenetic profile in this
      cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing
      uniform engraftment by three weeks with leukemic cells detectable in the
      peripheral blood spleen and bone marrow. These studies describe a new CLL cell
      line that extends currently available models to study gene function in this
      disease. 

PMID- 24130783
TI  - Diffusion microscopist simulator: a general Monte Carlo simulation system for
      diffusion magnetic resonance imaging.
AB  - This article describes the development and application of an integrated,
      generalized, and efficient Monte Carlo simulation system for diffusion magnetic
      resonance imaging (dMRI), named Diffusion Microscopist Simulator (DMS). DMS
      comprises a random walk Monte Carlo simulator and an MR image synthesizer. The
      former has the capacity to perform large-scale simulations of Brownian dynamics
      in the virtual environments of neural tissues at various levels of complexity,
      and the latter is flexible enough to synthesize dMRI datasets from a variety of
      simulated MRI pulse sequences. The aims of DMS are to give insights into the link
      between the fundamental diffusion process in biological tissues and the features
      observed in dMRI, as well as to provide appropriate ground-truth information for
      the development, optimization, and validation of dMRI acquisition schemes for
      different applications. The validity, efficiency, and potential applications of
      DMS are evaluated through four benchmark experiments, including the simulated
      dMRI of white matter fibers, the multiple scattering diffusion imaging, the
      biophysical modeling of polar cell membranes, and the high angular resolution
      diffusion imaging and fiber tractography of complex fiber configurations. We
      expect that this novel software tool would be substantially advantageous to
      clarify the interrelationship between dMRI and the microscopic characteristics of
      brain tissues, and to advance the biophysical modeling and the dMRI
      methodologies. 

PMID- 24130784
TI  - Validity of U.S. nutritional surveillance:National Health and Nutrition
      Examination Survey caloric energy intake data, 1971-2010.
AB  - IMPORTANCE: Methodological limitations compromise the validity of U.S.
      nutritional surveillance data and the empirical foundation for formulating
      dietary guidelines and public health policies. OBJECTIVES: Evaluate the validity
      of the National Health and Nutrition Examination Survey (NHANES) caloric intake
      data throughout its history, and examine trends in the validity of caloric intake
      estimates as the NHANES dietary measurement protocols evolved. DESIGN: Validity
      of data from 28,993 men and 34,369 women, aged 20 to 74 years from NHANES I (1971
      1974) through NHANES 2009-2010 was assessed by: calculating physiologically
      credible energy intake values as the ratio of reported energy intake (rEI) to
      estimated basal metabolic rate (BMR), and subtracting estimated total energy
      expenditure (TEE) from NHANES rEI to create 'disparity values'. MAIN OUTCOME
      MEASURES: 1) Physiologically credible values expressed as the ratio rEI/BMR and
      2) disparity values (rEI-TEE). RESULTS: The historical rEI/BMR values for men and
      women were 1.31 and 1.19, (95% CI: 1.30-1.32 and 1.18-1.20), respectively. The
      historical disparity values for men and women were -281 and -365 kilocalorie-per
      day, (95% CI: -299, -264 and -378, -351), respectively. These results are
      indicative of significant under-reporting. The greatest mean disparity values
      were -716 kcal/day and -856 kcal/day for obese (i.e., >=30 kg/m2) men and women,
      respectively. CONCLUSIONS: Across the 39-year history of the NHANES, EI data on
      the majority of respondents (67.3% of women and 58.7% of men) were not
      physiologically plausible. Improvements in measurement protocols after NHANES II
      led to small decreases in underreporting, artifactual increases in rEI, but only
      trivial increases in validity in subsequent surveys. The confluence of these
      results and other methodological limitations suggest that the ability to estimate
      population trends in caloric intake and generate empirically supported public
      policy relevant to diet-health relationships from U.S. nutritional surveillance
      is extremely limited.

PMID- 24130785
TI  - Efficient parallel Levenberg-Marquardt model fitting towards real-time automated
      parametric imaging microscopy.
AB  - We present a fast, accurate and robust parallel Levenberg-Marquardt minimization
      optimizer, GPU-LMFit, which is implemented on graphics processing unit for high
      performance scalable parallel model fitting processing. GPU-LMFit can provide a
      dramatic speed-up in massive model fitting analyses to enable real-time automated
      pixel-wise parametric imaging microscopy. We demonstrate the performance of GPU
      LMFit for the applications in superresolution localization microscopy and
      fluorescence lifetime imaging microscopy. 

PMID- 24130786
TI  - Cysteine residues in the major capsid protein, Vp1, of the JC virus are important
      for protein stability and oligomer formation.
AB  - The capsid of the human polyomavirus JC virus (JCV) consists of 72 pentameric
      capsomeres of a major structural protein, Vp1. The cysteine residues of the
      related Vp1 of SV40 are known to contribute to Vp1 folding, pentamer formation,
      pentamer-pentamer contacts, and capsid stabilization. In light of the presence of
      a slight structural difference between JCV Vp1 and SV40 counterpart, the way the
      former folds could be either different from or similar to the latter. We found a
      difference: an important contribution of Vp1 cysteines to the formation of
      infectious virions, unique in JCV and absent in SV40. Having introduced amino
      acid substitution at each of six cysteines (C42, C80, C97, C200, C247, and C260)
      in JCV Vp1, we found that, when expressed in HeLa cells, the Vp1 level was
      decreased in C80A and C247A mutants, and remained normal in the other mutants.
      Additionally, the C80A and C247A Vp1-expressing cell extracts did not show the
      hemagglutination activity characteristic of JCV particles. The C80A and C247A
      mutant Vp1s were found to be less stable than the wild-type Vp1 in HeLa cells.
      When produced in a reconstituted in vitro protein translation system, these two
      mutant proteins were stable, suggesting that some cellular factors were
      responsible for their degradation. As determined by their sucrose gradient
      sedimentation profiles, in vitro translated C247A Vp1 formed pentamers, but in
      vitro translated C80A Vp1 was entirely monomeric. When individually incorporated
      into the JCV genome, the C80A and C247A mutants, but not the other Vp1 cysteine
      residues mutants, interfered with JCV infectivity. Furthermore, the C80A, but not
      the C247A, mutation prevented the nuclear localization of Vp1 in JCV genome
      transfected cells. These findings suggest that C80 of JCV Vp1 is required for Vp1
      stability and pentamer formation, and C247 is involved in capsid assembly in the
      nucleus. 

PMID- 24130787
TI  - PMA and ionomycin induce glioblastoma cell death: activation-induced cell-death
      like phenomena occur in glioma cells.
AB  - Phorbol myristate acetate (PMA) and ionomycin (Io) can induce T cell activation
      and proliferation. Furthermore, they stimulate activation-induced cell death
      (AICD) in mature lymphocytes via Fas/Fas ligand (FasL) up-regulation. In this
      study, we explored the influence of PMA/Io treatment on glioblastoma cells, and
      found that AICD-like phenomena may also occur in glioma. Using the MTT assay and
      cell counting, we demonstrated that treatment of PMA/Io significantly inhibited
      the proliferation of glioma cell lines, U87 and U251. TUNEL assays and
      transmission electron microscopy revealed that PMA/Io markedly induced U87 and
      U251 cell apoptosis. Propidium iodide staining and flow cytometry showed that
      treatment with PMA/Io resulted in an arrestment of cell cycle and an increase in
      cell death. Using real-time PCR and western blot, we found that PMA/Io up
      regulated the expression of Fas and FasL at both mRNA and protein level, which
      confirmed that PMA/Io induced glioma cell death. Specific knockdown of NFAT1
      expression by small hairpin RNA greatly reduced the PMA/Io induced cell death and
      apoptosis by inhibition of FasL expression. Microarray analysis showed that the
      expression of NFAT1 significantly correlated with the expression of Fas. The
      coexistence of Fas with NFAT1 in vivo provides the background for AICD-like
      phenomena to occur in glioma. These findings demonstrate that PMA/Io can induce
      glioblastoma cell death through the NFAT1-Fas/FasL pathway. Glioma-related AICD
      like phenomena may provide a novel avenue for glioma treatment. 

PMID- 24130788
TI  - Characterizing the lymphopoietic kinetics and features of hematopoietic
      progenitors contained in the adult murine liver in vivo.
AB  - The appearance of donor-derived lymphocytes in liver transplant patients suggests
      that adult livers may contain cells capable of lymphopoiesis. However, only a few
      published studies have addressed the lymphopoietic capacity of adult liver cells,
      and its kinetics and features remain unclear. Herein, we investigated the
      lymphopoietic capacity of adult liver mononuclear cells (MNCs) and purified liver
      hematopoietic progenitor cells (HPCs) in vivo. Similar to bone-marrow
      transplantation (BMT), transplantation of liver MNCs alone was able to rescue
      survival of lethally irradiated mice. In terms of kinetics, liver MNC-derived
      myeloid lineage cells reconstituted more slowly than those from BMT. Liver MNC
      derived lymphocyte lineage cells in the blood, spleen and BM also reconstituted
      more slowly than BMT, but lymphocytes in the liver recovered at a similar rate.
      Interestingly, liver MNCs predominantly gave rise to CD3(+)CD19(-) T cells in
      both irradiated WT and non-irradiated lymphocyte-deficient Rag-1(-/-)Il2rg(-/-)
      recipients. To define the lymphopoietic potential of various cell populations
      within liver MNCs, we transplanted purified lineage-negative (Lin(-)) liver HPCs
      into recipient mice. Unlike total liver MNCs, liver HPCs reconstituted T and B
      cells in similar frequencies to BMT. We further determined that the predominance
      of T cells observed after transplanting total liver MNCs likely originated from
      mature T cells, as purified donor liver T cells proliferated in the recipients
      and gave rise to CD8(+) T cells. Thus, the capacity of donor adult liver cells to
      reconstitute lymphocytes in recipients derives from both HPCs and mature T cells
      contained in the liver MNC population. 

PMID- 24130789
TI  - Topical application of PPADS inhibits complement activation and choroidal
      neovascularization in a model of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most common cause of blindness
      among the elderly. AMD patients have elevated levels of membrane attack complex
      (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC
      forms pores in cell membranes. Low levels of MAC result in an elevation of
      cytokine release such as vascular endothelial growth factor (VEGF) that promotes
      the formation of choroidal neovascularization (CNV). High levels of MAC result in
      cell lysis and RPE degeneration is a hallmark of advanced AMD. The current
      standard of care for CNV associated with wet AMD is intravitreal injection of
      anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side
      effects. Recently, it has been found that membrane pore-forming proteins such as
      alpha-haemolysin can mediate their toxic effects through auto- and paracrine
      signaling and that complement-induced lysis is amplified through ATP release
      followed by P2X receptor activation. We hypothesized that attenuation of P2X
      receptor activation may lead to a reduction in MAC deposition and consequent
      formation of CNV. Hence, in this study we investigated topical application of the
      purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid
      (PPADS) as a potential treatment for AMD. We found that 4.17 uM PPADS inhibited
      formation of HUVEC master junctions and master segments by 74.7%. In a human
      complement mediated cell lysis assay, 104 uM PPADS enabled almost complete
      protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis.
      Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression
      of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the
      site of the laser injury by 19.7%. Our data have implications for the future
      treatment of AMD and potentially other ocular disorders involving CNV such as
      angioid streaks, choroidal rupture and high myopia. 

PMID- 24130790
TI  - Does my face FIT?: a face image task reveals structure and distortions of facial
      feature representation.
AB  - Despite extensive research on face perception, few studies have investigated
      individuals' knowledge about the physical features of their own face. In this
      study, 50 participants indicated the location of key features of their own face,
      relative to an anchor point corresponding to the tip of the nose, and the results
      were compared to the true location of the same individual's features from a
      standardised photograph. Horizontal and vertical errors were analysed separately.
      An overall bias to underestimate vertical distances revealed a distorted face
      representation, with reduced face height. Factor analyses were used to identify
      separable subconfigurations of facial features with correlated localisation
      errors. Independent representations of upper and lower facial features emerged
      from the data pattern. The major source of variation across individuals was in
      representation of face shape, with a spectrum from tall/thin to short/wide
      representation. Visual identification of one's own face is excellent, and facial
      features are routinely used for establishing personal identity. However, our
      results show that spatial knowledge of one's own face is remarkably poor,
      suggesting that face representation may not contribute strongly to self
      awareness. 

PMID- 24130791
TI  - Biochemical and structural characterization of SplD protease from Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a dangerous human pathogen. A number of the proteins
      secreted by this bacterium are implicated in its virulence, but many of the
      components of its secretome are poorly characterized. Strains of S. aureus can
      produce up to six homologous extracellular serine proteases grouped in a single
      spl operon. Although the SplA, SplB, and SplC proteases have been thoroughly
      characterized, the properties of the other three enzymes have not yet been
      investigated. Here, we describe the biochemical and structural characteristics of
      the SplD protease. The active enzyme was produced in an Escherichia coli
      recombinant system and purified to homogeneity. P1 substrate specificity was
      determined using a combinatorial library of synthetic peptide substrates showing
      exclusive preference for threonine, serine, leucine, isoleucine, alanine, and
      valine. To further determine the specificity of SplD, we used high-throughput
      synthetic peptide and cell surface protein display methods. The results not only
      confirmed SplD preference for a P1 residue, but also provided insight into the
      specificity of individual primed- and non-primed substrate-binding subsites. The
      analyses revealed a surprisingly narrow specificity of the protease, which
      recognized five consecutive residues (P4-P3-P2-P1-P1') with a consensus motif of
      R-(Y/W)-(P/L)-(T/L/I/V)?S. To understand the molecular basis of the strict
      substrate specificity, we crystallized the enzyme in two different conditions,
      and refined the structures at resolutions of 1.56 A and 2.1 A. Molecular modeling
      and mutagenesis studies allowed us to define a consensus model of substrate
      binding, and illustrated the molecular mechanism of protease specificity. 

PMID- 24130792
TI  - Diagnosing fatty liver disease: a comparative evaluation of metabolic markers,
      phenotypes, genotypes and established biomarkers.
AB  - BACKGROUND: To date, liver biopsy is the only means of reliable diagnosis for
      fatty liver disease (FLD). Owing to the inevitable biopsy-associated health
      risks, however, the development of valid noninvasive diagnostic tools for FLD is
      well warranted. AIM: We evaluated a particular metabolic profile with regard to
      its ability to diagnose FLD and compared its performance to that of established
      phenotypes, conventional biomarkers and disease-associated genotypes. METHODS:
      The study population comprised 115 patients with ultrasound-diagnosed FLD and 115
      sex- and age-matched controls for whom the serum concentration was measured of
      138 different metabolites, including acylcarnitines, amino acids, biogenic
      amines, hexose, phosphatidylcholines (PCs), lyso-PCs and sphingomyelins.
      Established phenotypes, biomarkers, disease-associated genotypes and metabolite
      data were included in diagnostic models for FLD using logistic regression and
      partial least-squares discriminant analysis. The discriminative power of the
      ensuing models was compared with respect to area under curve (AUC), integrated
      discrimination improvement (IDI) and by way of cross-validation (CV). RESULTS:
      Use of metabolic markers for predicting FLD showed the best performance among all
      considered types of markers, yielding an AUC of 0.8993. Additional information on
      phenotypes, conventional biomarkers or genotypes did not significantly improve
      this performance. Phospholipids and branched-chain amino acids were most
      informative for predicting FLD. CONCLUSION: We show that the inclusion of
      metabolite data may substantially increase the power to diagnose FLD over that of
      models based solely upon phenotypes and conventional biomarkers.

PMID- 24130793
TI  - Plasma haptoglobin concentrations are elevated in patients with coronary artery
      disease.
AB  - Inflammation underlies the development and progression of coronary artery
      plaques. Haptoglobin (Hp) is an acute phase protein, the synthesis of which is
      increased during inflammation. The aim of this study was to investigate plasma Hp
      concentrations and phenotype in patients with coronary artery disease (CAD). We
      recruited 359 patients with fixed luminal stenosis >=50% in at least one coronary
      artery (CAD group) and 83 patients with luminal stenosis <=40%, normal ejection
      fraction, and normal regional wall motion (control group). Plasma Hp
      concentrations were measured using a phenotype-specific enzyme-linked
      immunosorbent assay. Hp phenotype was determined by native polyacrylamide gel
      electrophoresis. Plasma lipid concentrations were measured. Plasma Hp
      concentrations were significantly higher in the CAD compared with the control
      group (262.4+/-144.2 vs 176.0+/-86.7 ng/mL, P<0.001); however, there was no
      between group difference in the distribution of Hp phenotype (1-1 = 7.5% vs 7.2%;
      2-1 = 40.4% vs 42.2%; 2-2 = 52.1% vs 50.6%). Stepwise multivariate logistic
      regression revealed that high Hp concentrations (odds ratio [OR] = 5.865), male
      sex (OR = 3.689), hypertension (OR = 2.632), diabetes mellitus (OR = 3.300), and
      low-density lipoprotein concentrations (OR = 1.480) were independently associated
      with CAD (all P<0.05). Hp phenotype was not associated with CAD. Plasma Hp
      concentrations were significantly correlated with the severity of luminal
      stenosis (r = 0.236, P<0.001). Our findings suggest that plasma Hp concentrations
      may be elevated in patients with CAD. There does not appear to be any
      relationship between Hp phenotype and CAD. 

PMID- 24130794
TI  - The novel PPAR alpha/gamma dual agonist MHY 966 modulates UVB-induced skin
      inflammation by inhibiting NF-kappaB activity.
AB  - Ultraviolet B (UVB; 290~320nm) irradiation-induced lipid peroxidation induces
      inflammatory responses that lead to skin wrinkle formation and epidermal
      thickening. Peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual
      agonists have the potential to be used as anti-wrinkle agents because they
      inhibit inflammatory response and lipid peroxidation. In this study, we evaluated
      the function of 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl) phenol (MHY 966), a
      novel synthetic PPAR alpha/gamma dual agonist, and investigated its anti
      inflammatory and anti-lipid peroxidation effects. The action of MHY 966 as a PPAR
      alpha/gamma dual agonist was also determined in vitro by reporter gene assay.
      Additionally, 8-week-old melanin-possessing hairless mice 2 (HRM2) were exposed
      to 150 mJ/cm(2) UVB every other day for 17 days and MHY 966 was simultaneously
      pre-treated every day for 17 days to investigate the molecular mechanisms
      involved. MHY 966 was found to stimulate the transcriptional activities of both
      PPAR alpha and gamma. In HRM2 mice, we found that the skins of mice exposed to
      UVB showed significantly increased pro-inflammatory mediator levels (NF-kappaB,
      iNOS, and COX-2) and increased lipid peroxidation, whereas MHY 966 co-treatment
      down-regulated these effects of UVB by activating PPAR alpha and gamma. Thus, the
      present study shows that MHY 966 exhibits beneficial effects on inflammatory
      responses and lipid peroxidation by simultaneously activating PPAR alpha and
      gamma. The major finding of this study is that MHY 966 demonstrates potential as
      an agent against wrinkle formation associated with chronic UVB exposure. 

PMID- 24130795
TI  - New findings in a global approach to dissect the whole phenotype of PLA2G6 gene
      mutations.
AB  - Mutations in PLA2G6 gene have variable phenotypic outcome including infantile
      neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic
      neurodegeneration with brain iron accumulation and Karak syndrome. The cause of
      this phenotypic variation is so far unknown which impairs both genetic diagnosis
      and appropriate family counseling. We report detailed clinical,
      electrophysiological, neuroimaging, histologic, biochemical and genetic
      characterization of 11 patients, from 6 consanguineous families, who were
      followed for a period of up to 17 years. Cerebellar atrophy was constant and the
      earliest feature of the disease preceding brain iron accumulation, leading to the
      provisional diagnosis of a recessive progressive ataxia in these patients.
      Ultrastructural characterization of patients' muscle biopsies revealed focal
      accumulation of granular and membranous material possibly resulting from
      defective membrane homeostasis caused by disrupted PLA2G6 function. Enzyme
      studies in one of these muscle biopsies provided evidence for a relatively low
      mitochondrial content, which is compatible with the structural mitochondrial
      alterations seen by electron microscopy. Genetic characterization of 11 patients
      led to the identification of six underlying PLA2G6 gene mutations, five of which
      are novel. Importantly, by combining clinical and genetic data we have observed
      that while the phenotype of neurodegeneration associated with PLA2G6 mutations is
      variable in this cohort of patients belonging to the same ethnic background, it
      is partially influenced by the genotype, considering the age at onset and the
      functional disability criteria. Molecular testing for PLA2G6 mutations is,
      therefore, indicated in childhood-onset ataxia syndromes, if neuroimaging shows
      cerebellar atrophy with or without evidence of iron accumulation. 

PMID- 24130796
TI  - Fenofibrate attenuated glucose-induced mesangial cells proliferation and
      extracellular matrix synthesis via PI3K/AKT and ERK1/2.
AB  - Excess mesangial extracellular matrix (ECM) and mesangial cell proliferation is
      the major pathologic feature of diabetic nephropathy (DN). Fenofibrate, a
      PPARalpha agonist, has been shown to attenuate extracellular matrix formation in
      diabetic nephropathy. However, the mechanisms underlying this effect remain to be
      elucidated. In this study, the effect of fenofibrate on high-glucose induced cell
      proliferation and extracellular matrix exertion and its mechanisms were
      investigated in cultured rat mesangial cells by the methylthiazoletetrazolium
      (MTT) assay, flow cytometry and western blot. The results showed that treatment
      of mesangial cells (MCs) with fenofibrate repressed high-glucose induced up
      regulation of extracellular matrix Collagen-IV, and inhibited entry of cell cycle
      into the S phase. This G1 arrest and ECM inhibition was caused by the reduction
      of phosphorylation and activation of extracellular signal-regulated kinase 1/2
      (ERK1/2) and AKT. On the contrary, PPARalpha siRNA accelerated high glucose
      induced cell cycle progression by ERK1/2 and AKT activation. Taken together,
      fenofibrate ameliorated glucose-induced mesangial cell proliferation and matrix
      production via its inhibition of PI3K/AKT and ERK1/2 signaling pathways. Such
      mechanisms may contribute to the favorable effects of treatment using fenofibrate
      in diabetic nephropathy. 

PMID- 24130797
TI  - Differential surface expression of ADAM10 and ADAM17 on human T lymphocytes and
      tumor cells.
AB  - A disintegrin and metalloproteases (ADAMs) have been implicated in many processes
      controlling organismic development and integrity. Important substrates of ADAM
      proteases include growth factors, cytokines and their receptors and adhesion
      proteins. The inducible but irreversible cleavage of their substrates alters cell
      cell communication and signaling. The crucial role of ADAM proteases (e.g. ADAM10
      and 17) for mammalian development became evident from respective knockout mice,
      that displayed pre- or perinatal lethality with severe defects in many organs and
      tissues. Although many substrates for these two ADAM proteases were identified
      over the last decade, the regulation of their surface appearance, their enzymatic
      activity and their substrate specificity are still not well understood. We
      therefore analyzed the constitutive and inducible surface expression of ADAM10
      and ADAM17 on a variety of human T cell and tumor cell lines. We demonstrate that
      ADAM10 is constitutively present at comparably high levels on the majority of the
      tested cell types. Stimulation with phorbol ester and calcium ionophore does not
      significantly alter the amount of surface ADAM10, except for a slight down
      regulation from T cell blasts. Using FasL shedding as a readout for ADAM10
      activity, we show that PKC activation and calcium mobilization are both
      prerequisite for activation of ADAM10 resulting in a production of soluble FasL.
      In contrast to ADAM10, the close relative ADAM17 is detected at only low levels
      on unstimulated cells. ADAM17 surface expression on T cell blasts is rapidly
      induced by stimulation. Since this inducible mobilization of ADAM17 is sensitive
      to inhibitors of actin filament formation, we propose that ADAM17 but not ADAM10
      is prestored in a subcellular compartment that is transported to the cell surface
      in an activation- and actin-dependent manner. 

PMID- 24130798
TI  - UV-light effects on cytochrome c modulated by the aggregation state of
      phenothiazines.
AB  - The present study shows the factors that modulate the photodamage promoted by
      phenothiazines. Cytochrome c was irradiated with UV light for 120 min, over a pH
      range from 4.0 to 8.0, in the absence and in the presence of different
      concentrations of thioridazine (TR) and fluphenazine (FP). In the absence of
      phenothiazines, the maximal rate of a Soret band blue shift (nm/min) from 409 to
      406 nm was obtained at pH 4.0 (0.028 nm/min). The presence of phenothiazines at
      the concentration range 10-25 umol/L amplified and accelerated a cytochrome c
      blue shift (409 to 405 nm, at a rate = 0.041 nm/min). Above 25 umol/L, crescent
      concentrations of phenothiazines contributed to cytochrome c protection with
      (maximal at 2500 umol/L). Scanning electronic microscopy revealed the formation
      of nanostructures. The pH also influenced the effect of low phenothiazine
      concentrations on cytochrome c. Thus, the predominance of phenothiazine-promoted
      cytochrome c damage or protection depends on a balance of the following factors:
      the yield of photo-generated drug cation radicals, which is favored by acidic pH;
      the stability of the cation radicals, which is favored by the drug aggregation;
      and the cytochrome c structure, modulated by the pH. 

PMID- 24130799
TI  - microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue
      from Japanese patients with persistent HCV versus HBV infection.
AB  - Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are
      incompletely defined but often assumed to be similar and related to immune
      mediated inflammation. Despite this, several studies hint at differences in
      expression of miR-122, a liver-specific microRNA with tumor suppressor
      properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus
      (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of
      miR-122 in these cancers would be of interest, as miR-122 is an essential host
      factor for HCV but not HBV replication. To determine whether the abundance of miR
      122 in cancer tissue is influenced by the nature of the underlying virus
      infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues
      from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was
      significantly reduced from normal in HBV-associated HCC, but not in liver cancer
      associated with HCV infection. This difference was independent of the degree of
      differentiation of the liver cancer. Surprisingly, we also found significant
      differences in miR-122 expression in non-tumor tissue, with miR-122 abundance
      reduced from normal in HCV- but not HBV-infected liver. Similar differences were
      observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese
      subjects, reductions in miR-122 abundance in non-tumor tissue were associated
      with a single nucleotide polymorphism near the IL28B gene that predicts poor
      response to interferon-based therapy (TG vs. TT genotype at rs8099917), and
      correlated negatively with the abundance of multiple interferon-stimulated gene
      transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be
      associated with endogenous interferon responses to the virus, while differences
      in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus
      specific mechanisms contributing to carcinogenesis. The continued expression of
      miR-122 in HCV-associated HCC may signify an important role for HCV replication
      late in the progression to malignancy. 

PMID- 24130801
TI  - Evaluation of live attenuated H7N3 and H7N7 vaccine viruses for their receptor
      binding preferences, immunogenicity in ferrets and cross reactivity to the novel
      H7N9 virus.
AB  - Live attenuated influenza vaccine (LAIV) candidates of the H7 subtype,
      A/Netherlands/219/03 (H7N7, NL03 ca) and A/chicken/British Columbia/CN-6/2004
      (H7N3, BC04 ca), were evaluated for their receptor binding specificity and
      immunogenicity in ferrets. The BC04 ca virus exhibited alpha2,3-SA and alpha2,6
      SA dual receptor binding preference while the NL03 ca virus preferentially bound
      to alpha2,3-SA. Substitution of the Q226 and G228 (Q-G) by the L226 and S228 (L
      S) residues in the HA improved binding to alpha2,6-SA for NL03 ca. The vaccine
      viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more
      efficiently than the original NL03 ca virus in the upper respiratory tract of
      ferrets, and induced higher levels of humoral and cellular immune responses.
      Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but
      did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3
      BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine
      immunized ferret sera cross reacted with the newly emerged H7N9 virus. These
      data, in combination with the safety data from previously conducted Phase 1
      studies, suggest that these vaccines may have a role in responding to the threat
      posed by the H7N9 virus. 

PMID- 24130800
TI  - Six innexins contribute to electrical coupling of C. elegans body-wall muscle.
AB  - C. elegans body-wall muscle cells are electrically coupled through gap junctions.
      Previous studies suggest that UNC-9 is an important, but not the only, innexin
      mediating the electrical coupling. Here we analyzed junctional current (I j ) for
      mutants of additional innexins to identify the remaining innexin(s) important to
      the coupling. The results suggest that a total of six innexins contribute to the
      coupling, including UNC-9, INX-1, INX-10, INX-11, INX-16, and INX-18. The I j
      deficiency in each mutant was rescued completely by expressing the corresponding
      wild-type innexin specifically in muscle, suggesting that the innexins function
      cell-autonomously. Comparisons of I j between various single, double, and triple
      mutants suggest that the six innexins probably form two distinct populations of
      gap junctions with one population consisting of UNC-9 and INX-18 and the other
      consisting of the remaining four innexins. Consistent with their roles in muscle
      electrical coupling, five of the six innexins showed punctate localization at
      muscle intercellular junctions when expressed as GFP- or epitope-tagged proteins,
      and muscle expression was detected for four of them when assessed by expressing
      GFP under the control of innexin promoters. The results may serve as a solid
      foundation for further explorations of structural and functional properties of
      gap junctions in C. elegans body-wall muscle. 

PMID- 24130802
TI  - Identification of candidate B-lymphoma genes by cross-species gene expression
      profiling.
AB  - Comparative genome-wide expression profiling of malignant tumor counterparts
      across the human-mouse species barrier has a successful track record as a gene
      discovery tool in liver, breast, lung, prostate and other cancers, but has been
      largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse
      large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene
      expression profiles of DLBCL-like tumors that arose spontaneously in Myc
      transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the
      human DLBCL transcriptome. The human and mouse lymphomas were found to have 60
      concordantly deregulated genes in common, including 8 genes that Cox hazard
      regression analysis associated with overall survival in a published landmark
      dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological
      validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a
      number of studies contending that FOXM1 is a therapeutic target in mature B cell
      tumors. Our findings demonstrate the value of the "mouse filter" for genomic
      studies of human B-lineage neoplasms for which a vast knowledge base already
      exists. 

PMID- 24130803
TI  - Transcriptome sequencing and expression analysis of terpenoid biosynthesis genes
      in Litsea cubeba.
AB  - BACKGROUND: Aromatic essential oils extracted from fresh fruits of Litsea cubeba
      (Lour.) Pers., have diverse medical and economic values. The dominant components
      in these essential oils are monoterpenes and sesquiterpenes. Understanding the
      molecular mechanisms of terpenoid biosynthesis is essential for improving the
      yield and quality of terpenes. However, the 40 available L. cubeba nucleotide
      sequences in the public databases are insufficient for studying the molecular
      mechanisms. Thus, high-throughput transcriptome sequencing of L. cubeba is
      necessary to generate large quantities of transcript sequences for the purpose of
      gene discovery, especially terpenoid biosynthesis related genes. RESULTS: Using
      Illumina paired-end sequencing, approximately 23.5 million high-quality reads
      were generated. De novo assembly yielded 68,648 unigenes with an average length
      of 834 bp. A total of 38,439 (56%) unigenes were annotated for their functions,
      and 35,732 and 25,806 unigenes could be aligned to the GO and COG database,
      respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes
      Pathway database (KEGG), 16,130 unigenes were assigned to 297 KEGG pathways, and
      61 unigenes, which contained the mevalonate and 2-C-methyl-D-erythritol 4
      phosphate pathways, could be related to terpenoid backbone biosynthesis. Of the
      12,963 unigenes, 285 were annotated to the terpenoid pathways using the PlantCyc
      database. Additionally, 14 terpene synthase genes were identified from the
      transcriptome. The expression patterns of the 16 genes related to terpenoid
      biosynthesis were analyzed by RT-qPCR to explore their putative functions.
      CONCLUSION: RNA sequencing was effective in identifying a large quantity of
      sequence information. To our knowledge, this study is the first exploration of
      the L. cubeba transcriptome, and the substantial amount of transcripts obtained
      will accelerate the understanding of the molecular mechanisms of essential oils
      biosynthesis. The results may help improve future genetic and genomics studies on
      the molecular mechanisms behind the chemical composition of essential oils in L.
      cubeba fruits.

PMID- 24130804
TI  - Transmission of Mycobacterium tuberculosis between farmers and cattle in central
      Ethiopia.
AB  - BACKGROUND: Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex
      could be possible between farmers and their cattle in Ethiopia.
      METHODOLOGY/PRINCIPAL FINDINGS: A study was conducted in mixed type multi
      purposes cattle raising region of Ethiopia on 287 households (146 households with
      case of pulmonary tuberculosis (TB) and 141 free of TB) and 287 herds consisting
      of 2,033 cattle belonging to these households to evaluate transmission of TB
      between cattle and farmers. Interview, bacteriological examinations and molecular
      typing were used for human subjects while comparative intradermal tuberculin
      (CIDT) test, post mortem and bacteriological examinations, and molecular typing
      were used for animal studies. Herd prevalence of CIDT reactors was 9.4% and was
      higher (p<0.01) in herds owned by households with TB than in herds owned by TB
      free households. Animal prevalence was 1.8% and also higher (p<0.01) in cattle
      owned by households with TB case than in those owned by TB free households. All
      mycobacteria (141) isolated from farmers were M. tuberculosis, while only five of
      the 16 isolates from cattle were members of the M. tuberculosis complex (MTC)
      while the remaining 11 were members of non-tuberculosis mycobacteria (NTM).
      Further speciation of the five MTC isolates showed that three of the isolates
      were M. bovis (strain SB1176), while the remaining two were M. tuberculosis
      strains (SIT149 and SIT53). Pathology scoring method described by "Vordermeier et
      al. (2002)" was applied and the average severity of pathology in two cattle
      infected with M. bovis, in 11 infected with NTM and two infected with M.
      tuberculosis were 5.5, 2.1 and 0.5, respectively. CONCLUSIONS/SIGNIFICANCE: The
      results showed that transmission of TB from farmers to cattle by the airborne
      route sensitizes the cows but rarely leads to TB. Similarly, low transmission of
      M. bovis between farmers and their cattle was found, suggesting requirement of
      ingestion of contaminated milk from cows with tuberculous mastitis.

PMID- 24130805
TI  - Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36
      recruitment into the same lipid rafts.
AB  - Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its
      differentiation into foam cells and cytokine production, contributing to
      atherosclerosis development. In a previous study, we showed that CD36 and the
      receptor for platelet-activating factor (PAFR) are required for oxLDL to activate
      gene transcription for cytokines and CD36. Here, we investigated the localization
      and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL.
      We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production.
      OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors
      (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts
      disruption by treatment with betaCD reduces the oxLDL uptake and IL-10
      production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the
      constitutive raft protein flotillin-1, and colocalization with the lipid raft
      marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in
      macrophages from human atherosclerotic plaques. Our results show that oxLDL
      induces the recruitment of PAFR and CD36 into the same lipid rafts, which is
      important for oxLDL uptake and IL-10 production. This study provided new insights
      into how oxLDL interact with macrophages and contributing to atherosclerosis
      development. 

PMID- 24130806
TI  - Targeting androgen receptor/Src complex impairs the aggressive phenotype of human
      fibrosarcoma cells.
AB  - BACKGROUND: Hormones and growth factors influence the proliferation and
      invasiveness of human mesenchymal tumors. The highly aggressive human
      fibrosarcoma HT1080 cell line harbors classical androgen receptor (AR) that
      responds to androgens triggering cell migration in the absence of significant
      mitogenesis. As occurs in many human cancer cells, HT1080 cells also express
      epidermal growth factor receptor (EGFR). EXPERIMENTAL:  FINDINGS: We report that
      the pure anti-androgen Casodex inhibits the growth of HT1080 cell xenografts in
      immune-depressed mice, revealing a novel role of AR in fibrosarcoma progression.
      In HT1080 cultured cells EGF, but not androgens, robustly increases DNA
      synthesis. Casodex abolishes the EGF mitogenic effect, implying a crosstalk
      between EGFR and AR. The mechanism underlying this crosstalk has been analyzed
      using an AR-derived small peptide, S1, which prevents AR/Src tyrosine kinase
      association and androgen-dependent Src activation. Present findings show that in
      HT1080 cells EGF induces AR/Src Association, and the S1 peptide abolishes both
      the assembly of this complex and Src activation. The S1 peptide inhibits EGF
      stimulated DNA synthesis, cell matrix metalloproteinase-9 (MMP-9) secretion and
      invasiveness of HT1080 cells. Both Casodex and S1 peptide also prevent DNA
      synthesis and migration triggered by EGF in various human cancer-derived cells
      (prostate, breast, colon and pancreas) that express AR. CONCLUSION: This study
      shows that targeting the AR domain involved in AR/Src association impairs EGF
      signaling in human fibrosarcoma HT1080 cells. The EGF-elicited processes
      inhibited by the peptide (DNA synthesis, MMP-9 secretion and invasiveness)
      cooperate in increasing the aggressive phenotype of HT1080 cells. Therefore, AR
      represents a new potential therapeutic target in human fibrosarcoma, as supported
      by Casodex inhibition of HT1080 cell xenografts. The extension of these findings
      in various human cancer-derived cell lines highlights the conservation of this
      process across divergent cancer cells and identifies new potential targets in the
      therapeutic approach to human cancers.

PMID- 24130807
TI  - S-adenosyl-homocysteine is a weakly bound inhibitor for a flaviviral
      methyltransferase.
AB  - The methyltransferase enzyme (MTase), which catalyzes the transfer of a methyl
      group from S-adenosyl-methionine (AdoMet) to viral RNA, and generates S-adenosyl
      homocysteine (AdoHcy) as a by-product, is essential for the life cycle of many
      significant human pathogen flaviviruses. Here we investigated inhibition of the
      flavivirus MTase by several AdoHcy-derivatives. Unexpectedly we found that AdoHcy
      itself barely inhibits the flavivirus MTase activities, even at high
      concentrations. AdoHcy was also shown to not inhibit virus growth in cell
      culture. Binding studies confirmed that AdoHcy has a much lower binding affinity
      for the MTase than either the AdoMet co-factor, or the natural AdoMet analog
      inhibitor sinefungin (SIN). While AdoMet is a positively charged molecule, SIN is
      similar to AdoHcy in being uncharged, and only has an additional amine group that
      can make extra electrostatic contacts with the MTase. Molecular Mechanics Poisson
      Boltzmann Sovation Area analysis on AdoHcy and SIN binding to the MTase suggests
      that the stronger binding of SIN may not be directly due to interactions of this
      amine group, but due to distributed differences in SIN binding resulting from its
      presence. The results suggest that better MTase inhibitors could be designed by
      using SIN as a scaffold rather than AdoHcy. 

PMID- 24130808
TI  - Conditional deletion of ERK5 MAP kinase in the nervous system impairs pheromone
      information processing and pheromone-evoked behaviors.
AB  - ERK5 MAP kinase is highly expressed in the developing nervous system but absent
      in most regions of the adult brain. It has been implicated in regulating the
      development of the main olfactory bulb and in odor discrimination. However,
      whether it plays an essential role in pheromone-based behavior has not been
      established. Here we report that conditional deletion of the Mapk7 gene which
      encodes ERK5 in mice in neural stem cells impairs several pheromone-mediated
      behaviors including aggression and mating in male mice. These deficits were not
      caused by a reduction in the level of testosterone, by physical immobility, by
      heightened fear or anxiety, or by depression. Using mouse urine as a natural
      pheromone-containing solution, we provide evidence that the behavior impairment
      was associated with defects in the detection of closely related pheromones as
      well as with changes in their innate preference for pheromones related to sexual
      and reproductive activities. We conclude that expression of ERK5 during
      development is critical for pheromone response and associated animal behavior in
      adult mice. 

PMID- 24130809
TI  - Genetic background can result in a marked or minimal effect of gene knockout
      (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of
      multiple sclerosis.
AB  - Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid
      receptors, transient receptor potential vanilloid one (TRPV1) receptor and the
      orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6
      (Cnr2 (tm1Zim)) CB2 cannabinoid receptor knockout mice have demonstrated an
      immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE)
      models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often
      failed to show any treatment effect of either CB2 receptor agonism or antagonism
      on inhibition of T cell autoimmunity. The influence of genetic background on the
      induction of EAE in endocannabinoid system-related gene knockout mice was
      examined. It was found that C57BL/6.GPR55 knockout mice developed less severe
      disease, notably in female mice, following active induction with myelin
      oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen))
      receptor knockout mice developed augmented severity of disease consistent with
      the genetically and pharmacologically-distinct, Cnr2 (tm1Zim) mice. However, when
      the knockout gene was bred into the ABH mouse background and EAE induced with
      spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was
      lost. Likewise CB1 receptor and transient receptor potential vanilloid one
      knockout mice on the ABH background demonstrated no alteration in immune
      susceptibility, in terms of disease incidence and severity of EAE, in contrast to
      that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating
      influence of GPR55 was marginal on the ABH mouse background. Whilst sedative
      doses of tetrahydrocannabinol could induce immunosuppression, this was associated
      with a CB1 receptor rather than a CB2 receptor-mediated effect. These data
      support the fact that non-psychoactive doses of medicinal cannabis have a
      marginal influence on the immune response in MS. Importantly, it adds a note of
      caution for the translational value of some transgenic/gene knockout and other
      studies on low-EAE susceptibility backgrounds with inconsistent disease course
      and susceptibility. 

PMID- 24130810
TI  - The -607C/A polymorphisms in interleukin-18 gene promoter contributes to cancer
      risk: evidence from a meta-analysis of 22 case-control studies.
AB  - BACKGROUND: Several observational studies have investigated the association
      between -607 C/A polymorphism of IL-18 gene and cancer risk; however, the results
      were inconsistent. Therefore, we performed a meta-analysis to derive a more
      precise estimation of the association to help us better understand the
      relationship between -607 C/A polymorphism of IL-18 gene promoter and risk of
      cancer. METHODS: A literature search was carried out using PubMed, EMBASE, and
      China National Knowledge Infrastructure (CNKI) database between January 1966 and
      February 2013. Fixed-effect and random-effect models were used to estimate the
      pooled odds ratio (OR) and the corresponding 95% confidence intervals (CIs).
      RESULTS: A total of 22 case-control studies including 4100 cancer cases and 4327
      controls contributed to the analysis. Significant association between -607C/A
      polymorphism in IL-18 gene promoter and cancer risk was observed (CA vs CC:OR
      =1.221, 95% CI: 1.096, 1.360; P(heterogeneity)=0.219; AA/CA vs. CC:OR =1.203, 95%
      CI: 1.057, 1.369; P(heterogeneity)=0.064). In the subgroup analysis by ethnicity,
      -607C/A polymorphism significantly increased risk of cancer among Asian
      population (AA/CA vs. CC:OR =1.197, 95% CI: 1.023,1.401; P(heterogeneity)=0.088);
      however, no significant association was found in Caucasian or African population.
      The -607C/A polymorphism was associated with a significantly increased risk of
      nasopharyngeal carcinoma (CA vs CC:OR =1.330, 95% CI: 1.029,1.719;
      P(heterogeneity)=0.704; AA/CA vs. CC:OR =1.323, 95% CI: 1.037,1.687;
      P(heterogeneity)=0.823) and esophageal cancer (AA/CA vs. CC:OR =1.289, 95% CI:
      1.002,1.658; P(heterogeneity)=0.700). CONCLUSIONS: The present meta-analysis
      suggests that the -607C/A polymorphisms in IL-18 gene promoter is associated with
      a significantly increased risk of cancer, especially for nasopharyngeal carcinoma
      and esophageal cancer and in Asian population. More studies with larger sample
      size, well controlled confounding factors are warranted to validate this
      association.

PMID- 24130811
TI  - The ComP-ComA quorum system is essential for "Trojan horse" like pathogenesis in
      Bacillus nematocida.
AB  - Bacillus nematocida B16 has been shown to use "Trojan horse" mechanism in
      pathogenesis that has characteristics of "social" behavior. The ComP-ComA system,
      a conserved quorum sensing system in the genus Bacillus, functions in many
      physiological processes including competence development, lipopeptide antibiotic
      surfactin production, degradative enzyme production and even some unknown
      functions. Here we investigated the requirement of ComP-ComA system in B.
      nematocida B16 for its pathogenicity against nematodes. The DeltacomP mutant
      displayed deficiencies in attracting and killing nematodes, due to the absence of
      attractive signal molecules and the decreased expressions of virulence factors,
      respectively. Contrarily, a complemented comP mutant at least partially resumed
      its pathogenicity. Our data from transcriptional analysis further confirmed that
      this signaling system directly or indirectly regulated the expressions of two
      major virulence proteases in the infection of B. nematocida B16. Bioinformatics
      analyses from comparative genomics also suggested that the potential target genes
      of transcription factor ComA were involved in the processes such as the synthesis
      of attractants, production of extracellular degradative enzymes and sortase,
      secondary metabolites biosynthesis, regulation of transcription factors,
      mobility, as well as transporters, most of which were different from a
      saprophytic relative B. subtilis 168. Therefore, our investigation firstly
      revealed that the participation and necessity of ComP-ComA signaling system in
      bacterial pathogenesis. 

PMID- 24130812
TI  - Imbricaric acid and perlatolic acid: multi-targeting anti-inflammatory depsides
      from Cetrelia monachorum.
AB  - In vitro screening of 17 Alpine lichen species for their inhibitory activity
      against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor
      kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As
      conceivable source for novel anti-inflammatory compounds. Phytochemical
      investigation of the ethanolic crude extract resulted in the isolation and
      identification of 11 constituents, belonging to depsides and derivatives of
      orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid
      (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal
      prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 uM, resp.) and on 5-lipoxygenase
      tested in a cell-based assay (IC50 = 5.3 and 1.8 uM, resp.) and on purified
      enzyme (IC50 = 3.5 and 0.4 uM, resp.). Additionally, these two main constituents
      quantified in the extract with 15.22% (4) and 9.10% (5) showed significant
      inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B
      activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 uM,
      respectively. In a murine in vivo model of inflammation, 5 impaired the
      inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum.
      The potent inhibitory effects on the three identified targets attest 4 and 5 a
      pronounced multi-target anti-inflammatory profile which warrants further
      investigation on their pharmacokinetics and in vivo efficacy. 

PMID- 24130813
TI  - The influence of interspecific competition and host preference on the
      phylogeography of two African ixodid tick species.
AB  - A comparative phylogeographic study on two economically important African tick
      species, Amblyomma hebraeum and Hyalomma rufipes was performed to test the
      influence of host specificity and host movement on dispersion. Pairwise AMOVA
      analyses of 277 mtDNA COI sequences supported significant population
      differentiation among the majority of sampling sites. The geographic
      mitochondrial structure was not supported by nuclear ITS-2 sequencing, probably
      attributed to a recent divergence. The three-host generalist, A. hebraeum, showed
      less mtDNA geographic structure, and a lower level of genetic diversity, while
      the more host-specific H. rufipes displayed higher levels of population
      differentiation and two distinct mtDNA assemblages (one predominantly confined to
      South Africa/Namibia and the other to Mozambique and East Africa). A zone of
      overlap is present in southern Mozambique. A mechanistic climate model suggests
      that climate alone cannot be responsible for the disruption in female gene flow.
      Our findings furthermore suggest that female gene dispersal of ticks is more
      dependent on the presence of juvenile hosts in the environment than on the
      ability of adult hosts to disperse across the landscape. Documented interspecific
      competition between the juvenile stages of H. rufipes and H. truncatum is
      implicated as a contributing factor towards disrupting gene flow between the two
      southern African H. rufipes genetic assemblages. 

PMID- 24130814
TI  - Validation of verbal autopsy tool for ascertaining the causes of stillbirth.
AB  - OBJECTIVE: To assess performance of the WHO revised verbal autopsy tool for
      ascertaining the causes of still birth in comparison with reference standard
      cause of death ascertained by standardized clinical and supportive data. METHODS:
      All stillbirths at a tertiary hospital in Karachi, Pakistan were prospectively
      recruited into study from August 2006- February 2008. The reference standard
      cause of death was established by two senior obstetricians within 48 hours using
      the ICD coding system. Verbal autopsy interviews using modified WHO tool were
      conducted by trained health workers within 2- 6 weeks of still birth and the
      cause of death was assigned by second panel of obstetricians. The performance was
      assessed in terms of sensitivity, specificity and Kappa. RESULTS: There were 204
      still births. Of these, 80.8% of antepartum and 50.5% of intrapartum deaths were
      correctly diagnosed by verbal autopsy. Sensitivity of verbal autopsy was highest
      68.4%, (95%CI: 46-84.6) for congenital malformation followed by obstetric
      complication 57.6%, (95%CI: 25-84.2). The specificity for all major causes was
      greater than 90%. The level of agreement was high (kappa=0.72) for anomalies and
      moderate (k=0.4) for all major causes of still birth, except asphyxia.
      CONCLUSION: Our results suggest that verbal autopsy has reasonable validity in
      identifying and discriminating between causes of stillbirth in Pakistan. On the
      basis of these findings, we feel it has a place in resource constrained areas to
      inform strategic planning and mobilization of resources to attain Millennium
      Development Goals.

PMID- 24130816
TI  - Deep bisulfite sequencing of aberrantly methylated loci in a patient with
      multiple methylation defects.
AB  - NLRP7 is a maternal effect gene as maternal mutations in this gene cause
      recurrent hydatidiform moles, spontaneous abortions and stillbirths, whereas live
      births are very rare. We have studied a patient with multiple anomalies born to a
      mother with a heterozygous NLRP7 mutation. By array-based CpG methylation
      analysis of blood DNA from the patient, his parents and 18 normal controls on
      Illumina Infinium HumanMethylation27 BeadChips we found that the patient had
      methylation changes (delta beta >= 0.3) at many imprinted loci as well as at 87
      CpGs associated with 85 genes of unknown imprinting status. Using a pseudoproband
      (permutation) approach, we found methylation changes at only 7-24 CpGs (mean 15;
      standard deviation 4.84) in the controls. Thus, the number of abberantly
      methylated CpGs in the patient is more than 14 standard deviations higher. In
      order to identify novel imprinted genes among the 85 conspicuous genes in the
      patient, we selected 19 (mainly hypomethylated) genes for deep bisulfite amplicon
      sequencing on the ROCHE/454 Genome Sequencer in the patient and at least two
      additional controls. These controls had not been included in the array analysis
      and were heterozygous for a single nucleotide polymorphism at the test locus, so
      that allele-specific DNA methylation patterns could be determined. Apart from
      FAM50B, which we proved to be imprinted in blood, we did not observe allele
      specific DNA methylation at the other 18 loci. We conclude that the patient does
      not only have methylation defects at imprinted loci but (at least in blood) also
      an excess of methylation changes at apparently non-imprinted loci. 

PMID- 24130815
TI  - Liver-specific expressions of HBx and src in the p53 mutant trigger
      hepatocarcinogenesis in zebrafish.
AB  - Hepatocarcinogenesis is a multistep process that starts from fatty liver and
      transitions to fibrosis and, finally, into cancer. Many etiological factors,
      including hepatitis B virus X antigen (HBx) and p53 mutations, have been
      implicated in hepatocarcinogenesis. However, potential synergistic effects
      between these two factors and the underlying mechanisms by which they promote
      hepatocarcinogenesis are still unclear. In this report, we show that the
      synergistic action of HBx and p53 mutation triggers progressive hepatocellular
      carcinoma (HCC) formation via src activation in zebrafish. Liver-specific
      expression of HBx in wild-type zebrafish caused steatosis, fibrosis and glycogen
      accumulation. However, the induction of tumorigenesis by HBx was only observed in
      p53 mutant fish and occurred in association with the up-regulation and activation
      of the src tyrosine kinase pathway. Furthermore, the overexpression of src in p53
      mutant zebrafish also caused hyperplasia, HCC, and sarcomatoid HCC, which were
      accompanied by increased levels of the signaling proteins p-erk, p-akt, myc, jnk1
      and vegf. Increased expression levels of lipogenic factors and the genes involved
      in lipid metabolism and glycogen storage were detected during the early stages of
      hepatocarcinogenesis in the HBx and src transgenic zebrafish. The up-regulation
      of genes involved in cell cycle regulation, tumor progression and other molecular
      hallmarks of human liver cancer were found at later stages in both HBx and src
      transgenic, p53 mutant zebrafish. Together, our study demonstrates that HBx and
      src overexpression induced hepatocarcinogenesis in p53 mutant zebrafish. This
      phenomenon mimics human HCC formation and provides potential in vivo platforms
      for drug screening for therapies for human liver cancer. 

PMID- 24130817
TI  - The impact of baseline serum C-reactive protein and C-reactive protein kinetics
      on the prognosis of metastatic nasopharyngeal carcinoma patients treated with
      palliative chemotherapy.
AB  - BACKGROUND: The aim of this study was to determine whether baseline C-reactive
      protein (CRP) levels and CRP kinetics predict the overall survival in metastatic
      nasopharyngeal carcinoma (mNPC) patients. METHODS: A total of 116 mNPC patients
      from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was
      measured at baseline and thereafter at the start of each palliative chemotherapy
      cycle for all patients. RESULTS: Patients with higher values of baseline CRP (>=
      3.4 mg/L) had significantly worse survival than those with lower baseline CRP
      values (< 3.4 mg/L). Patients were divided into four groups according to baseline
      CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during
      treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time
      during treatment; (3) patients whose CRP >= 3.4 mg/L and normalized at least one
      time during treatment; and (4) patients whose CRP >= 3.4 mg/L and never
      normalized during treatment. The patients were further assigned to non-elevated,
      elevated, normalized, and non-normalized CRP groups. Overall survival rates were
      significantly different among the four groups, with three-year survival rates of
      68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non
      normalized CRP groups respectively. When compared with the non-elevated group,
      hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated,
      and non-normalized groups (P < 0.001). CONCLUSIONS: Baseline CRP and CRP kinetics
      may be useful to predict the prognosis of metastatic NPC patients treated with
      palliative chemotherapy and facilitate individualized treatment. A prospective
      study to validate this prognostic model is still needed however.

PMID- 24130818
TI  - Nutlin-3a decreases male fertility via UQCRC2.
AB  - Ubiquinol-cytochrome-c reductase core protein 2 (UQCRC2) is a component of
      ubiquinol-cytochrome c reductase complex that is known to correlate with male
      fertility via spermatogenesis. Simultaneously, nutlin-3a is a small molecule
      antagonist of mouse double minute 2 repressor (MDM2), activate p53 and induce
      apoptosis responsible for spermatogenesis. To date, however there are no known
      effects of nutlin-3a on reproduction. Therefore, present study was designed to
      investigate the effect of nutlin-3a on male fertility via UQCRC2. In this in
      vitro trial with mice spermatozoa, we utilized CASA, CTC staining, ATP assay,
      western blotting, and IVF to measure the main study outcome. The short-term
      exposure of spermatozoa in nutlin-3a decreases sperm motion kinematics,
      intracellular ATP production, capacitation, the acrosome reaction, UQCRC2, and
      tyrosine phosphorylation (TYP) of sperm proteins in a dose-dependent manner.
      Notably, the decreased UQCRC2 and TYP were associated with reduced sperm
      kinematics, ATP production, and capacitation, which ultimately led to adverse
      effects on male fertility such as poor fertilization rates and embryo
      development. Thus, nutlin-3a may be considered as a potential male contraceptive
      agent due to its ability to decrease fertility secondary to changes in overall
      sperm physiology and embryonic development. However, the results of this
      preliminary study have to be confirmed by additional independent trial. 

PMID- 24130819
TI  - No association between TGFB1 polymorphisms and late radiotherapy toxicity: a meta
      analysis.
AB  - BACKGROUND: Transforming growth factor-beta 1 (TGF-beta1) protein may be
      multifunctional and related to the development of fibrosis, induction of
      apoptosis, extracellular signaling and inhibition of proliferation in response to
      radiation-induced DNA damage. Several studies have investigated associations
      between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late
      radiation-induced injury of normal tissue, but the conclusions remain
      controversial. METHODS: We searched three electronic databases (i.e., MEDLINE,
      EMBASE and EBSCO) for eligible publications and performed a meta-analysis
      assessing the association of three commonly studied SNPs in TGFB1 (i.e.,
      rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of
      normal tissue. RESULTS: We finally included 28 case-only studies from 16
      publications on aforementioned SNPs in TGFB1. However, we did not find
      statistical evidence of any significant association with overall risk of late
      radiotherapy toxicity in the pooled analysis or in further stratified analysis by
      cancer type, endpoint, ethnicity and sample size. CONCLUSIONS: This meta-analysis
      did not find statistical evidence for an association between SNPs in TGFB1 and
      risk of late radiation-induced injury of normal tissue, but this finding needs
      further confirmation by a single large study.

PMID- 24130820
TI  - Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns
      Disease.
AB  - BACKGROUND: Development of inflammatory bowel disease (IBD) involves the
      interplay of environmental and genetic factors with the host immune system.
      Mechanisms contributing to immune dysregulation in IBD are not fully defined.
      Development of novel therapeutic strategies is focused on controlling aberrant
      immune response in IBD. Current IBD therapy utilizes a combination of
      immunomodulators and biologics to suppress pro-inflammatory effectors of IBD.
      However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not
      well understood. The goal of this study was to examine the association between
      ANXA1 and IBD, and the effects of anti-TNF-alpha, Infliximab (IFX), therapy on
      ANXA1 expression. METHODS: ANXA1 and TNF-alpha transcript levels in PBMC were
      measured by RT PCR. Clinical follow up included the administration of serial
      ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1
      levels were measured by ELISA. RESULTS: We found that the reduction in ANXA1
      protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression
      in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX
      therapy in patients with a successful intervention but not in clinical non
      responders. The IFX therapy also modified the cellular immune activation in the
      peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in
      the colonic mucosa of IBD patients with incomplete resolution of inflammation
      during continuous therapy, which correlated with increased levels of TNF-alpha
      transcripts. Gut mucosal epithelial barrier disruption was evident by increased
      plasma bacterial 16S levels. CONCLUSION: Loss of ANXA1 expression may support
      inflammation during IBD and can serve as a biomarker of disease progression.
      Changes in ANXA1 levels may be predictive of therapeutic efficacy.

PMID- 24130821
TI  - Retromer dependent recycling of the Wnt secretion factor Wls is dispensable for
      stem cell maintenance in the mammalian intestinal epithelium.
AB  - In C. elegans and Drosophila, retromer mediated retrograde transport of Wntless
      (Wls) from endosomes to the trans-Golgi network (TGN) is required for Wnt
      secretion. When this retrograde transport pathway is blocked, Wls is missorted to
      lysosomes and degraded, resulting in reduced Wnt secretion and various Wnt
      related phenotypes. In the mammalian intestine, Wnt signaling is essential to
      maintain stem cells. This prompted us to ask if retromer mediated Wls recycling
      is also important for Wnt signaling and stem cell maintenance in this system. To
      answer this question, we generated a conditional Vps35 (fl) allele. As Vps35 is
      an essential subunit of the retromer complex, this genetic tool allowed us to
      inducibly interfere with retromer function in the intestinal epithelium. Using a
      pan-intestinal epithelial Cre line (Villin-CreERT2), we did not observe defects
      in crypt or villus morphology after deletion of Vps35 from the intestinal
      epithelium. Wnt secreted from the mesenchyme of the intestine may compensate for
      a reduction in epithelial Wnt secretion. To exclude the effect of the mesenchyme,
      we generated intestinal organoid cultures. Loss of Vps35 in intestinal organoids
      did not affect the overall morphology of the organoids. We were able to culture
      Vps35 (?/?) organoids for many passages without Wnt supplementation in the growth
      medium. However, Wls protein levels were reduced and we observed a subtle growth
      defect in the Vps35 (?/?) organoids. These results confirm the role of retromer
      in the retrograde trafficking of Wls in the intestine, but show that retromer
      mediated Wls recycling is not essential to maintain Wnt signaling or stem cell
      proliferation in the intestinal epithelium. 

PMID- 24130822
TI  - Fecal microbiota and metabolome of children with autism and pervasive
      developmental disorder not otherwise specified.
AB  - This study aimed at investigating the fecal microbiota and metabolome of children
      with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and
      autism (AD) in comparison to healthy children (HC). Bacterial tag-encoded FLX
      titanium amplicon pyrosequencing (bTEFAP) of the 16S rDNA and 16S rRNA analyses
      were carried out to determine total bacteria (16S rDNA) and metabolically active
      bacteria (16S rRNA), respectively. The main bacterial phyla (Firmicutes,
      Bacteroidetes, Fusobacteria and Verrucomicrobia) significantly (P<0.05) changed
      among the three groups of children. As estimated by rarefaction, Chao and Shannon
      diversity index, the highest microbial diversity was found in AD children. Based
      on 16S-rRNA and culture-dependent data, Faecalibacterium and Ruminococcus were
      present at the highest level in fecal samples of PDD-NOS and HC children.
      Caloramator, Sarcina and Clostridium genera were the highest in AD children.
      Compared to HC, the composition of Lachnospiraceae family also differed in PDD
      NOS and, especially, AD children. Except for Eubacterium siraeum, the lowest
      level of Eubacteriaceae was found on fecal samples of AD children. The level of
      Bacteroidetes genera and some Alistipes and Akkermansia species were almost the
      highest in PDD-NOS or AD children as well as almost all the identified
      Sutterellaceae and Enterobacteriaceae were the highest in AD. Compared to HC
      children, Bifidobacterium species decreased in AD. As shown by Canonical
      Discriminant Analysis of Principal Coordinates, the levels of free amino acids
      and volatile organic compounds of fecal samples were markedly affected in PDD-NOS
      and, especially, AD children. If the gut microbiota differences among AD and PDD
      NOS and HC children are one of the concomitant causes or the consequence of
      autism, they may have implications regarding specific diagnostic test, and/or for
      treatment and prevention. 

PMID- 24130823
TI  - Maize root lectins mediate the interaction with Herbaspirillum seropedicae via N
      acetyl glucosamine residues of lipopolysaccharides.
AB  - Herbaspirillum seropedicae is a plant growth-promoting diazotrophic
      betaproteobacterium which associates with important crops, such as maize, wheat,
      rice and sugar-cane. We have previously reported that intact lipopolysaccharide
      (LPS) is required for H. seropedicae attachment and endophytic colonization of
      maize roots. In this study, we present evidence that the LPS biosynthesis gene
      waaL (codes for the O-antigen ligase) is induced during rhizosphere colonization
      by H. seropedicae. Furthermore a waaL mutant strain lacking the O-antigen portion
      of the LPS is severely impaired in colonization. Since N-acetyl glucosamine
      inhibits H. seropedicae attachment to maize roots, lectin-like proteins from
      maize roots (MRLs) were isolated and mass spectrometry (MS) analysis showed that
      MRL-1 and MRL-2 correspond to maize proteins with a jacalin-like lectin domain,
      while MRL-3 contains a B-chain lectin domain. These proteins showed agglutination
      activity against wild type H. seropedicae, but failed to agglutinate the waaL
      mutant strain. The agglutination reaction was severely diminished in the presence
      of N-acetyl glucosamine. Moreover addition of the MRL proteins as competitors in
      H. seropedicae attachment assays decreased 80-fold the adhesion of the wild type
      to maize roots. The results suggest that N-acetyl glucosamine residues of the LPS
      O-antigen bind to maize root lectins, an essential step for efficient bacterial
      attachment and colonization. 

PMID- 24130824
TI  - T lymphocytes from chronic HCV-infected patients are primed for activation
      induced apoptosis and express unique pro-apoptotic gene signature.
AB  - Although extensive studies have demonstrated the functional impairment of antigen
      specific CD4(+) and CD8(+) T-cells during chronic hepatitis C virus (HCV)
      infection, the functional status of global CD4(+) and CD8(+) T-cells remains
      unclear. In this report, we recruited 42 long-term (~20 years) treatment-naive
      chronic HCV (CHC) patients and 15 healthy donors (HDs) to investigate differences
      in global CD4(+) and CD8(+) T-cells function. We show that CD4(+) and CD8(+) T
      cells from CHC patients underwent increased apoptosis after TCR stimulation.
      Furthermore, IFN-gamma, IL-9 and IP-10 were elevated in CHC patients' plasma and
      promoted activation-induced T-cells death. Global CD4(+) and CD8(+) T-cells also
      showed unique transcriptional profiles in the expression of apoptosis-related
      genes. We identified BCL2, PMAIP1, and CASP1 in CD4(+) T-cells and IER3 and
      BCL2A1 in CD8(+) T-cells from CHC patients as HCV-specific gene signatures.
      Importantly, the gene expression patterns of CD4(+) and CD8(+) T-cells from CHC
      patients differ from those in CD4(+) and CD8(+) T-cells from human
      immunodeficiency virus type 1 (HIV-1) or hepatitis B virus (HBV) infected
      individuals. Our results indicate that chronic HCV infection causes a systemic
      change in cytokine levels that primes T-cells for activation-induced apoptosis.
      Furthermore, HCV infection programs unique apoptosis-related gene expression
      profiles in CD4(+) and CD8(+) T-cells, leading to their enhanced activation
      induced apoptosis. These results provide novel insights to the pathogenesis of
      chronic HCV infection. 

PMID- 24130825
TI  - Polymorphic homoeolog of key gene of RdDM pathway, ARGONAUTE4_9 class is
      associated with pre-harvest sprouting in wheat (Triticum aestivum L.).
AB  - Resistance to pre-harvest sprouting (PHS) is an important objective for the
      genetic improvement of many cereal crops, including wheat. Resistance, or
      susceptibility, to PHS is mainly influenced by seed dormancy, a complex trait.
      Reduced seed dormancy is the most important aspect of seed germination on a spike
      prior to harvesting, but it is influenced by various environmental factors
      including light, temperature and abiotic stresses. The basic genetic framework of
      seed dormancy depends on the antagonistic action of abscisic acid (ABA) and
      gibberellic acid (GA) to promote dormancy and germination. Recent studies have
      revealed a role for epigenetic changes, predominantly histone modifications, in
      controlling seed dormancy. To investigate the role of DNA methylation in seed
      dormancy, we explored the role of ARGONAUTE4_9 class genes in seed development
      and dormancy in wheat. Our results indicate that the two wheat AGO4_9 class genes
      i.e. AGO802 and AGO804 map to chromosomes 3L and 1L are preferentially expressed
      in the embryos of developing seeds [corrected]. Differential expressions of
      AGO802-B in the embryos of PHS resistant and susceptible varieties also relates
      with DNA polymorphism in various wheat varieties due to an insertion of a SINE
      like element into this gene. DNA methylation patterns of the embryonic tissue
      from six PHS resistant and susceptible varieties demonstrate a correlation with
      this polymorphism. These results suggest a possible role for AGO802-B in seed
      dormancy and PHS resistance through the modulation of DNA methylation.

PMID- 24130826
TI  - Phylogeography and conservation genetics of a distinct lineage of sunfish in the
      Cuatro Cienegas valley of Mexico.
AB  - The valley of Cuatro Cienegas, an aquatic oasis located in the Mexican Chihuahuan
      Desert, exhibits the highest level of endemism in North America and is a Mexican
      National Protected Area. However, little is known about the evolutionary
      distinctiveness of several vertebrate species present in the Cuatro Cienegas
      valley. We conducted a phylogeographic study using mitochondrial haplotypes from
      the centrarchid fish Lepomis megalotis to determine if the populations found
      within the valley were evolutionarily distinct from populations outside the
      valley. We also examined if there was evidence of unique haplotypes of this
      sunfish within the valley. Genetic divergence of L. megalotis suggests
      populations within the valley are evolutionarily unique when compared to L.
      megalotis outside the valley. Significant mitochondrial sequence divergence was
      also discovered between L. megalotis populations on either side of the Sierra de
      San Marcos that bisects the valley. Our results reinforce previous studies that
      suggest the organisms occupying aquatic habitats not only within Cuatro Cienegas
      but also in each of the two lobes of the valley generally deserve independent
      consideration during management decisions. 

PMID- 24130827
TI  - Pregnancy incidence and risk factors among women participating in vaginal
      microbicide trials for HIV prevention: systematic review and meta-analysis.
AB  - INTRODUCTION: Pregnancy is contraindicated in vaginal microbicide trials for the
      prevention of HIV infection in women due to the unknown maternal and fetal safety
      of the microbicides. Women who become pregnant are taken off the microbicide
      during pregnancy period but this result in reduction of the power of the trials.
      Strategies to reduce the pregnancy rates require an understanding of the
      incidence and associated risk factors of pregnancy in microbicide trials. This
      systematic review estimates the overall incidence rate of pregnancy in
      microbicide trials and describes the associated risk factors. METHODS: A
      comprehensive literature search was carried out to identify eligible studies from
      electronic databases and other sources. Two review authors independently selected
      studies and extracted relevant data from included studies. Meta-analysis of
      incidence rates of pregnancy was carried out and risk factors of pregnancy were
      reported narratively. RESULTS: Fifteen studies reporting data from 10 microbicide
      trials (N=27,384 participants) were included. A total of 4,107 participants
      (15.0%) fell pregnant and a meta-analysis of incidence rates of pregnancy from 8
      microbicide trials (N=25,551) yielded an overall incidence rate of 23.37 (95%CI:
      17.78 to 28.96) pregnancies per 100 woman-years. However, significant
      heterogeneity was detected. Hormonal injectable, intra-uterine device (IUD) or
      implants or sterilization, older age, more years of education and condom use were
      associated with lower pregnancy. On the other hand, living with a man, history of
      pregnancy, self and partner desire for future baby, oral contraceptive use,
      increased number of unprotected sexual acts and inconsistent use of condoms were
      associated with higher pregnancy. CONCLUSIONS: The incidence rate of pregnancy in
      microbicide trials is high and strategies for its reduction are urgently required
      in order to improve the sample size and power of these trials.

PMID- 24130828
TI  - BCL-3 attenuation of TNFA expression involves an incoherent feed-forward loop
      regulated by chromatin structure.
AB  - Induction of genes is rarely an isolated event; more typically occurring as part
      of a web of parallel interactions, or motifs, which act to refine and control
      gene expression. Here, we define an Incoherent Feed-forward Loop motif in which
      TNFalpha-induced NF-kappaB signalling activates expression of the TNFA gene
      itself and also controls synthesis of the negative regulator BCL-3. While sharing
      a common inductive signal, the two genes have distinct temporal expression
      profiles. Notably, while the TNFA gene promoter is primed to respond immediately
      to activated NF-kappaB in the nucleus, induction of BCL3 expression only occurs
      after a time delay of about 1h. We show that this time delay is defined by
      remodelling of the BCL3 gene promoter, which is required to activate gene
      expression, and characterise the chromatin delayed induction of BCL3 expression
      using mathematical models. The models show how a delay in inhibitor production
      effectively uncouples the rate of response to inflammatory cues from the final
      magnitude of inhibition. Hence, within this regulatory motif, a delayed
      (incoherent) feed-forward loop together with differential rates of TNFA (fast)
      and BCL3 (slow) mRNA turnover provide robust, pulsatile expression of TNFalpha .
      We propose that the structure of the BCL-3-dependent regulatory motif has a
      beneficial role in modulating expression dynamics and the inflammatory response
      while minimising the risk of pathological hyper-inflammation. 

PMID- 24130829
TI  - Solution NMR structure and histone binding of the PHD domain of human MLL5.
AB  - Mixed Lineage Leukemia 5 (MLL5) is a histone methyltransferase that plays a key
      role in hematopoiesis, spermatogenesis and cell cycle progression. In addition to
      its catalytic domain, MLL5 contains a PHD finger domain, a protein module that is
      often involved in binding to the N-terminus of histone H3. Here we report the NMR
      solution structure of the MLL5 PHD domain showing a variant of the canonical PHD
      fold that combines conserved H3 binding features from several classes of other
      PHD domains (including an aromatic cage) along with a novel C-terminal alpha
      helix, not previously seen. We further demonstrate that the PHD domain binds with
      similar affinity to histone H3 tail peptides di- and tri-methylated at lysine 4
      (H3K4me2 and H3K4me3), the former being the putative product of the MLL5
      catalytic reaction. This work establishes the PHD domain of MLL5 as a bone fide
      'reader' domain of H3K4 methyl marks suggesting that it may guide the spreading
      or further methylation of this site on chromatin. 

PMID- 24130830
TI  - HLA class I and II expression in oropharyngeal squamous cell carcinoma in
      relation to tumor HPV status and clinical outcome.
AB  - HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has
      better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment
      may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation,
      additional markers are needed together with HPV status to better predict
      treatment response. Here the influence of HLA class I/HLA class II expression was
      explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009
      and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and
      HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a
      very favorable disease-free survival (DFS), disease-specific survival (DSS) and
      overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate
      analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with
      absent/weak HLA class I responded equally well when treated with induction-chemo
      radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC,
      high HLA class I/class II expression correlated in general to a better clinical
      outcome. p16(INK4a) overexpression correlated to a better clinical outcome in
      HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very
      high survival independent of treatment and could possibly be used clinically to
      select patients for randomized trials de-escalating therapy. 

PMID- 24130831
TI  - Framing political messages to fit the audience's regulatory orientation: how to
      improve the efficacy of the same message content.
AB  - This research investigates how the impact of persuasive messages in the political
      domain can be improved when fit is created by subliminally priming recipients'
      regulatory focus (either promotion or prevention) and by linguistic framing of
      the message (either strategic approach framing or strategic avoidance framing).
      Results of two studies show that regulatory fit: a) increases the impact of a
      political message favoring nuclear energy on implicit attitudes of the target
      audience (Study 1); and b) induces a more positive evaluation of, and intentions
      to vote for, the political candidate who is delivering a message concerning
      immigration policies (Study 2). 

PMID- 24130832
TI  - Differently environment stable bio-silver nanoparticles: study on their optical
      enhancing and antibacterial properties.
AB  - Generally, limited research is extended in studying stability and applicational
      properties of silver nanoparticles (Ag NPs) synthesized by adopting 'green
      chemistry' protocol. In this work, we report on the synthesis of stable Ag NPs
      using plant-derived materials such as leaf extract of Neem (Azadirachta indica)
      and biopolymer pectin from apple peel. In addition, the applicational properties
      of Ag NPs such as surface-enhanced Raman scattering (SERS) and antibacterial
      efficiencies were also investigated. As-synthesized nanoparticles (NPs) were
      characterized using various instrumentation techniques. Both the plant materials
      (leaf extract and biopolymer) favored the synthesis of well-defined NPs capped
      with biomaterials. The NPs were spherical in shape with an average particle size
      between 14-27 nm. These bio-NPs exhibited colloidal stability in most of the
      suspended solutions such as water, electrolyte solutions (NaCl; NaNO3),
      biological solution (bovine serum albumin), and in different pH solutions (pH 7;
      9) for a reasonable time period of 120 hrs. Both the bio-NPs were observed to be
      SERS active through displaying intrinsic SERS signals of the Raman probe molecule
      (Nile blue A). The NPs were effective against the Escherichia coli bacterium when
      tested in nutrient broth and agar medium. Scanning and high-resolution
      transmission electron microscopy (SEM and HRTEM) images confirmed cellular
      membrane damage of nanoparticle treated E. coli cells. These environmental
      friendly template Ag NPs can be used as an antimicrobial agent and also for SERS
      based analytical applications. 

PMID- 24130833
TI  - Fn14*TRAIL effectively inhibits hepatocellular carcinoma growth.
AB  - BACKGROUND: New strategies for the treatment of hepatocellular carcinoma (HCC)
      are needed, given that currently available chemotherapeutics are inefficient.
      Since tumor growth reflects the net balance between pro-proliferative and death
      signaling, agents shifting the equilibrium toward the latter are of considerable
      interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and
      tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively
      induce apoptosis in malignant cells. Fn14*TRAIL, a fusion protein bridging these
      two pathways, has the potential to inhibit tumor growth, by interfering with
      TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated
      apoptosis. Consequently, Fn14*TRAIL's capacity to inhibit HCC growth was tested.
      RESULTS: Fn14*TRAIL induced robust apoptosis of multiple HCC cell lines, while
      sparing non-malignant hepatocyte cell lines. Differential susceptibility to this
      agent did not correlate with expression levels of TRAIL, TRAIL-R, TWEAK and Fn14
      by these lines. Fn14*TRAIL was more potent than soluble TRAIL, soluble Fn14, or a
      combination of the two. The requirement of both of Fn14*TRAIL's molecular domains
      for function was established using blocking antibodies directed against each of
      them. Subcutaneous injection of Fn14*TRAIL abrogated HCC growth in a xenograft
      model, and was well tolerated by the mice. CONCLUSIONS: In this study,
      Fn14*TRAIL, a multifunctional fusion protein originally designed to treat
      autoimmunity, was shown to inhibit the growth of HCC, both in vitro and in vivo.
      The demonstration of this fusion protein's potent anti-tumor activity suggests
      that simultaneous targeting of two signaling axes by a single fusion can serve as
      a basis for highly effective anti-cancer therapies.

PMID- 24130834
TI  - Profiling of the mammalian mitotic spindle proteome reveals an ER protein, OSTD
      1, as being necessary for cell division and ER morphology.
AB  - Cell division is important for many cellular processes including cell growth,
      reproduction, wound healing and stem cell renewal. Failures in cell division can
      often lead to tumors and birth defects. To identify factors necessary for this
      process, we implemented a comparative profiling strategy of the published mitotic
      spindle proteome from our laboratory. Of the candidate mammalian proteins, we
      determined that 77% had orthologs in Caenorhabditis elegans and 18% were
      associated with human disease. Of the C. elegans candidates (n=146), we
      determined that 34 genes functioned in embryonic development and 56% of these
      were predicted to be membrane trafficking proteins. A secondary, visual screen to
      detect distinct defects in cell division revealed 21 genes that were necessary
      for cytokinesis. One of these candidates, OSTD-1, an ER resident protein, was
      further characterized due to the aberrant cleavage furrow placement and failures
      in division. We determined that OSTD-1 plays a role in maintaining the dynamic
      morphology of the ER during the cell cycle. In addition, 65% of all ostd-1 RNAi
      treated embryos failed to correctly position cleavage furrows, suggesting that
      proper ER morphology plays a necessary function during animal cell division. 

PMID- 24130835
TI  - Characterization of Liaoning cashmere goat transcriptome: sequencing, de novo
      assembly, functional annotation and comparative analysis.
AB  - BACKGROUND: Liaoning cashmere goat is a famous goat breed for cashmere wool. In
      order to increase the transcriptome data and accelerate genetic improvement for
      this breed, we performed de novo transcriptome sequencing to generate the first
      expressed sequence tag dataset for the Liaoning cashmere goat, using next
      generation sequencing technology. RESULTS: Transcriptome sequencing of Liaoning
      cashmere goat on a Roche 454 platform yielded 804,601 high-quality reads.
      Clustering and assembly of these reads produced a non-redundant set of 117,854
      unigenes, comprising 13,194 isotigs and 104,660 singletons. Based on similarity
      searches with known proteins, 17,356 unigenes were assigned to 6,700 GO
      categories, and the terms were summarized into three main GO categories and 59
      sub-categories. 3,548 and 46,778 unigenes had significant similarity to existing
      sequences in the KEGG and COG databases, respectively. Comparative analysis
      revealed that 42,254 unigenes were aligned to 17,532 different sequences in NCBI
      non-redundant nucleotide databases. 97,236 (82.51%) unigenes were mapped to the
      30 goat chromosomes. 35,551 (30.17%) unigenes were matched to 11,438 reported
      goat protein-coding genes. The remaining non-matched unigenes were further
      compared with cattle and human reference genes, 67 putative new goat genes were
      discovered. Additionally, 2,781 potential simple sequence repeats were initially
      identified from all unigenes. CONCLUSION: The transcriptome of Liaoning cashmere
      goat was deep sequenced, de novo assembled, and annotated, providing abundant
      data to better understand the Liaoning cashmere goat transcriptome. The potential
      simple sequence repeats provide a material basis for future genetic linkage and
      quantitative trait loci analyses.

PMID- 24130836
TI  - Molecular characterization of the alpha-subunit of Na+/K+ ATPase from the
      euryhaline barnacle Balanus improvisus reveals multiple genes and differential
      expression of alternative splice variants.
AB  - The euryhaline bay barnacle Balanus improvisus has one of the broadest salinity
      tolerances of any barnacle species. It is able to complete its life cycle in
      salinities close to freshwater (3 PSU) up to fully marine conditions (35 PSU) and
      is regarded as one of few truly brackish-water species. Na+/K+ ATPase (NAK) has
      been shown to be important for osmoregulation when marine organisms are
      challenged by changing salinities, and we therefore cloned and examined the
      expression of different NAKs from B. improvisus. We found two main gene variants,
      NAK1 and NAK2, which were approximately 70% identical at the protein level. The
      NAK1 mRNA existed in a long and short variant with the encoded proteins differing
      only by 27 N-terminal amino acids. This N-terminal stretch was coded for by a
      separate exon, and the two variants of NAK1 mRNAs appeared to be created by
      alternative splicing. We furthermore showed that the two NAK1 isoforms were
      differentially expressed in different life stages and in various tissues of adult
      barnacle, i.e the long isoform was predominant in cyprids and in adult cirri. In
      barnacle cyprid larvae that were exposed to a combination of different salinities
      and pCO2 levels, the expression of the long NAK1 mRNA increased relative to the
      short in low salinities. We suggest that the alternatively spliced long variant
      of the Nak1 protein might be of importance for osmoregulation in B. improvisus in
      low salinity conditions.

PMID- 24130837
TI  - Enhanced expression of long non-coding RNA HOTAIR is associated with the
      development of gastric cancer.
AB  - The long non-coding RNA HOTAIR has been reported to be a poor prognostic
      biomarker in a variety of malignant tumors. However, little is known about the
      association of HOTAIR with gastric cancer. We examined the expression of HOTAIR
      in 68 gastric cancer samples using quantitative real-time RT-PCR and analyzed its
      correlation with the clinical parameters. The functional role of HOTAIR was
      examined by generating human gastric cancer cell lines with increased or
      suppressed HOTAIR expression. The anchorage -independent growth was assessed by
      soft agar assay. The increased or suppressed HOTAIR expressing gastric cancer
      cells were injected into the tail vein or peritoneal cavity of immunodeficient
      mice to examine the effect of this molecule on metastasis and peritoneal
      dissemination. The expression of HOTAIR was significantly higher in cancer
      lesions than in adjacent non-cancerous tissues in human gastric cancers. In the
      diffuse type of gastric cancer, the High-HOTAIR group (HOTAIR/GAPDH > 1) showed
      significantly more venous invasion, frequent lymph node metastases and a lower
      overall survival rate compared to the Low-HOTAIR group (HOTAIR/GAPDH < 1). Colony
      formation on the soft agar was enhanced in a HOTAIR-dependent manner. HOTAIR
      expressing MKN74 formed more liver metastasis compared to control when they were
      injected into the tail vein of mice. In addition, reduced expression of HOTAIR in
      KATO III suppressed peritoneal dissemination. These results suggest that HOTAIR
      plays a pivotal role in the development of gastric cancer. 

PMID- 24130838
TI  - Marine sediment-derived Streptomyces bacteria from British Columbia, Canada are a
      promising microbiota resource for the discovery of antimicrobial natural
      products.
AB  - Representatives of the genus Streptomyces from terrestrial sources have been the
      focus of intensive research for the last four decades because of their prolific
      production of chemically diverse and biologically important compounds. However,
      metabolite research from this ecological niche had declined significantly in the
      past years because of the rediscovery of the same bioactive compounds and
      redundancy of the sample strains. More recently, a new picture has begun to
      emerge in which marine-derived Streptomyces bacteria have become the latest hot
      spot as new source for unique and biologically active compounds. Here, we
      investigated the marine sediments collected in the temperate cold waters from
      British Columbia, Canada as a valuable source for new groups of marine-derived
      Streptomyces with antimicrobial activities. We performed culture dependent
      isolation from 49 marine sediments samples and obtained 186 Streptomyces
      isolates, 47 of which exhibited antimicrobial activities. Phylogenetic analyses
      of the active isolates resulted in the identification of four different clusters
      of bioactive Streptomyces including a cluster with isolates that appear to
      represent novel species. Moreover, we explored whether these marine-derived
      Streptomyces produce new secondary metabolites with antimicrobial properties.
      Chemical analyses revealed structurally diverse secondary metabolites, including
      four new antibacterial novobiocin analogues. We conducted structure-activity
      relationships (SAR) studies of these novobiocin analogues against methicillin
      resistant Staphylococcus aureus (MRSA). In this study, we revealed the importance
      of carbamoyl and OMe moieties at positions 3" and 4" of novobiose as well as the
      hydrogen substituent at position 5 of hydroxybenzoate ring for the anti-MRSA
      activity. Changes in the substituents at these positions dramatically impede or
      completely eliminate the inhibitory activity of novobiocins against MRSA. 

PMID- 24130839
TI  - Transcriptome comparison between porcine subcutaneous and intramuscular stromal
      vascular cells during adipogenic differentiation.
AB  - Intramuscular fat (IMF) is an important trait influencing meat quality, and
      preadipocyte differentiation is a key factor affecting IMF deposition. Here we
      compared the transcriptome profiles of porcine intramuscular and subcutaneous
      preadipocytes during differentiation to gain insight into specific molecular and
      cellular events associated with intramuscular stromal vascular cell (MSVC)
      differentiation. RNA-Seq was used to screen for differentially expressed genes
      (DEGs) during the in vitro differentiation of MSVC and subcutaneous stromal
      vascular cell (ASVC) on days 0, 2 and 4. A total of 985 DEGs were identified
      during ASVC differentiation and 1469 DEGs during MSVC differentiation. Among
      these DEGs, 409 genes were specifically expressed during ASVC differentiation,
      893 genes were specifically expressed during MSVC differentiation, and 576 DEGs
      were co-expressed during ASVC and MSVC differentiation. The expression profiles
      of DEGs during ASVC or MSVC differentiation were determined by cluster analysis
      based on Short Time-series Expression Miner (STEM). Four significant STEM
      profiles (profiles 1, 4, 5, and 14) were determined during ASVC differentiation,
      and four significant STEM profiles (profiles 1, 4, 11, and 14) were determined
      during MSVC differentiation. Gene ontology (GO) analysis indicated that DEGs
      related to adipocyte differentiation were identified to be significantly enriched
      in both adipose and muscle profile 14. In addition, Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathway analysis of DEGs in adipose profile 14 and muscle
      profiles 11 and 14 (STEM clustered them into one cluster) showed that the PPAR
      signaling pathway was significantly enriched in these profiles and four signaling
      pathways were specifically enriched in muscle profiles 11 and 14. Furthermore,
      analysis of transcription factor binding sites (TFBS) in the gene set revealed
      two over-represented transcription factors (NR3C4 and NR3C1), which were
      specifically significantly enriched in the promoter regions of genes within
      muscle gene expression profiles 11 and 14. 

PMID- 24130840
TI  - Comparison of manual and automated measurements of monodominant follicle diameter
      with different follicle size in infertile patients.
AB  - This study evaluated the consistency of manual and automated measurements of
      monodominant follicle diameter with different follicle size in infertile
      patients. Transvaginal two-dimensional (2D) ultrasound and SonoAVC (Sonography
      based Automated Volume Calculation) were both performed in 226 infertile patients
      with monodominant follicle growth. 2D diameters were separately compared with
      SonoAVC-generated d(V) and m-d values in different follicle category, i.e. >10 to
      14 mm, >14 to 18 mm, >18 to 22 mm and >22 mm. There was moderate degree of
      consistency between 2D diameter and SonoAVC-generated parameters regardless of
      follicle size. The mean differences were 0.82 mm between 2D diameter and SonoAVC
      generated d(V) value, and 0.22 mm between 2D diameter and SonoAVC-generated m-d
      value, respectively. The discrepancy of manual and automated measurements tended
      to increase as follicle size increased. Our study suggested that compared with
      manual measurement, SonoAVC might underestimate follicle size. The absolute size
      of a follicle affected the consistency of two techniques. 

PMID- 24130841
TI  - A role for cytosolic isocitrate dehydrogenase as a negative regulator of glucose
      signaling for insulin secretion in pancreatic beta-cells.
AB  - Cytosolic NADPH may act as one of the signals that couple glucose metabolism to
      insulin secretion in the pancreatic beta-cell. NADPH levels in the cytoplasm are
      largely controlled by the cytosolic isoforms of malic enzyme and isocitrate
      dehydrogenase (IDHc). Some studies have provided evidence for a role of malic
      enzyme in glucose-induced insulin secretion (GIIS) via pyruvate cycling, but the
      role of IDHc in beta-cell signaling is unsettled. IDHc is an established
      component of the isocitrate/alpha-ketoglutarate shuttle that transfers reducing
      equivalents (NADPH) from the mitochondrion to the cytosol. This shuttle is energy
      consuming since it is coupled to nicotinamide nucleotide transhydrogenase that
      uses the mitochondrial proton gradient to produce mitochondrial NADPH and NAD(+)
      from NADP(+) and NADH. To determine whether flux through IDHc is positively or
      negatively linked to GIIS, we performed RNAi knockdown experiments in beta-cells.
      Reduced IDHc expression in INS 832/13 cells and isolated rat islet beta-cells
      resulted in enhanced GIIS. This effect was mediated at least in part via the KATP
      independent amplification arm of GIIS. IDHc knockdown in INS 832/13 cells did not
      alter glucose oxidation but it reduced fatty acid oxidation and increased
      lipogenesis from glucose. Metabolome profiling in INS 832/13 cells showed that
      IDHc knockdown increased isocitrate and NADP(+) levels. It also increased the
      cellular contents of several metabolites linked to GIIS, in particular some Krebs
      cycle intermediates, acetyl-CoA, glutamate, cAMP and ATP. The results identify
      IDHc as a component of the emerging pathways that negatively regulate GIIS. 

PMID- 24130842
TI  - Rho GTPases and regulation of cell migration and polarization in human corneal
      epithelial cells.
AB  - PURPOSE: Epithelial cell migration is required for regeneration of tissues and
      can be defective in a number of ocular surface diseases. This study aimed to
      determine the expression pattern of Rho family small G-proteins in human corneal
      epithelial cells to test their requirement in directional cell migration.
      METHODS: Rho family small G-protein expression was assessed by reverse
      transcription-polymerase chain reaction. Dominant-inhibitory constructs encoding
      Rho proteins or Rho protein targeting small interfering RNA were transfected into
      human corneal epithelial large T antigen cells, and wound closure rate were
      evaluated by scratch wounding assay, and a complementary non-traumatic cell
      migration assay. Immunofluorescence staining was performed to study cell
      polarization and to assess Cdc42 downstream effector. RESULTS: Cdc42, Chp, Rac1,
      RhoA, TC10 and TCL were expressed in human corneal epithelial cells. Among them,
      Cdc42 and TCL were found to significantly affect cell migration in monolayer
      scratch assays. These results were confirmed through the use of validated siRNAs
      directed to Cdc42 and TCL. Scramble siRNA transfected cells had high percentage
      of polarized cells than Cdc42 or TCL siRNA transfected cells at the wound edge.
      We showed that the Cdc42-specific effector p21-activated kinase 4 localized
      predominantly to cell-cell junctions in cell monolayers, but failed to
      translocate to the leading edge in Cdc42 siRNA transfected cells after monolayer
      wounding. CONCLUSION: Rho proteins expressed in cultured human corneal epithelial
      cells, and Cdc42, TCL facilitate two-dimensional cell migration in-vitro.
      Although silencing of Cdc42 and TCL did not noticeably affect the appearance of
      cell adhesions at the leading edge, the slower migration of these cells indicates
      both GTP-binding proteins play important roles in promoting cell movement of
      human corneal epithelial cells.

PMID- 24130843
TI  - Combined genetic and telemetry data reveal high rates of gene flow, migration,
      and long-distance dispersal potential in Arctic ringed seals (Pusa hispida).
AB  - Ringed seals (Pusa hispida) are broadly distributed in seasonally ice covered
      seas, and their survival and reproductive success is intricately linked to sea
      ice and snow. Climatic warming is diminishing Arctic snow and sea ice and
      threatens to endanger ringed seals in the foreseeable future. We investigated the
      population structure and connectedness within and among three subspecies: Arctic
      (P. hispida hispida), Baltic (P. hispida botnica), and Lake Saimaa (P. hispida
      saimensis) ringed seals to assess their capacity to respond to rapid
      environmental changes. We consider (a) the geographical scale of migration, (b)
      use of sea ice, and (c) the amount of gene flow between subspecies. Seasonal
      movements and use of sea ice were determined for 27 seals tracked via satellite
      telemetry. Additionally, population genetic analyses were conducted using 354
      seals representative of each subspecies and 11 breeding sites. Genetic analyses
      included sequences from two mitochondrial regions and genotypes of 9
      microsatellite loci. We found that ringed seals disperse on a pan-Arctic scale
      and both males and females may migrate long distances during the summer months
      when sea ice extent is minimal. Gene flow among Arctic breeding sites and between
      the Arctic and the Baltic Sea subspecies was high; these two subspecies are
      interconnected as are breeding sites within the Arctic subspecies. 

PMID- 24130845
TI  - Chemosignals of stress influence social judgments.
AB  - Human body odors have important communicative functions regarding genetic
      identity, immune fitness and general health, but an expanding body of research
      suggests they can also communicate information about an individual's emotional
      state. In the current study, we tested whether axillary odors obtained from women
      experiencing psychosocial stress could negatively influence personality judgments
      of warmth and competence made about other women depicted in video scenarios. 44
      female donors provided three types of sweat samples: untreated exercise sweat,
      untreated stress sweat and treated stress sweat. After a 'washout' period, a
      commercial unscented anti-perspirant product was applied to the left axilla only
      to evaluate whether 'blocking' the stress signal would improve the social
      evaluations. A separate group of male and female evaluators (n = 120) rated the
      women in the videos while smelling one of the three types of sweat samples. Women
      in the video scenes were rated as being more stressed by both men and women when
      smelling the untreated vs. treated stress sweat. For men only, the women in the
      videos were rated as less confident, trustworthy and competent when smelling both
      the untreated stress and exercise sweat in contrast to the treated stress sweat.
      Women's social judgments were unaffected by sniffing the pads. The results have
      implications for influencing multiple types of professional and personal social
      interactions and impression management and extend our understanding of the social
      communicative function of body odors. 

PMID- 24130844
TI  - Oxidative stress induced mitochondrial protein kinase A mediates cytochrome c
      oxidase dysfunction.
AB  - Previously we showed that Protein kinase A (PKA) activated in hypoxia and
      myocardial ischemia/reperfusion mediates phosphorylation of subunits I, IVi1 and
      Vb of cytochrome c oxidase. However, the mechanism of activation of the kinase
      under hypoxia remains unclear. It is also unclear if hypoxic stress activated PKA
      is different from the cAMP dependent mitochondrial PKA activity reported under
      normal physiological conditions. In this study using RAW 264.7 macrophages and in
      vitro perfused mouse heart system we investigated the nature of PKA activated
      under hypoxia. Limited protease treatment and digitonin fractionation of intact
      mitochondria suggests that higher mitochondrial PKA activity under hypoxia is
      mainly due to increased sequestration of PKA Catalytic alpha (PKAalpha) subunit
      in the mitochondrial matrix compartment. The increase in PKA activity is
      independent of mitochondrial cAMP and is not inhibited by adenylate cyclase
      inhibitor, KH7. Instead, activation of hypoxia-induced PKA is dependent on
      reactive oxygen species (ROS). H89, an inhibitor of PKA activity and the
      antioxidant Mito-CP prevented loss of CcO activity in macrophages under hypoxia
      and in mouse heart under ischemia/reperfusion injury. Substitution of wild type
      subunit Vb of CcO with phosphorylation resistant S40A mutant subunit attenuated
      the loss of CcO activity and reduced ROS production. These results provide a
      compelling evidence for hypoxia induced phosphorylation as a signal for CcO
      dysfunction. The results also describe a novel mechanism of mitochondrial PKA
      activation which is independent of mitochondrial cAMP, but responsive to ROS. 

PMID- 24130846
TI  - A target-disease network model of second-generation BCR-ABL inhibitor action in
      Ph+ ALL.
AB  - Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is in
      part driven by the tyrosine kinase bcr-abl, but imatinib does not produce long
      term remission. Therefore, second-generation ABL inhibitors are currently in
      clinical investigation. Considering different target specificities and the
      pronounced genetic heterogeneity of Ph+ ALL, which contributes to the
      aggressiveness of the disease, drug candidates should be evaluated with regard to
      their effects on the entire Ph+ ALL-specific signaling network. Here, we applied
      an integrated experimental and computational approach that allowed us to estimate
      the differential impact of the bcr-abl inhibitors nilotinib, dasatinib, Bosutinib
      and Bafetinib. First, we determined drug-protein interactions in Ph+ ALL cell
      lines by chemical proteomics. We then mapped those interactions along with known
      genetic lesions onto public protein-protein interactions. Computation of global
      scores through correlation of target affinity, network topology, and distance to
      disease-relevant nodes assigned the highest impact to dasatinib, which was
      subsequently confirmed by proliferation assays. In future, combination of patient
      specific genomic information with detailed drug target knowledge and network
      based computational analysis should allow for an accurate and individualized
      prediction of therapy. 

PMID- 24130847
TI  - Ecological aspects of phlebotomine sandflies (Diptera: Psychodidae) from a cave
      of the speleological province of Bambui, Brazil.
AB  - Phlebotomines are invertebrate hosts of Leishmania genus species which are
      etiological agents of leishmaniases in humans and other mammals. Sandflies are
      often collected in entomological studies of caves both in the inner area and the
      adjacent environments. Caves are ecotypes clearly different from the external
      environment. Several caves have been opened to public visitation before any
      studies were performed and the places do not have scientific monitoring of the
      fauna, flora, geological and geographical characteristics. These events can lead
      to the loss of geological and biological information. Considering these aspects,
      this study aimed to describe the sand fly fauna, including the ecological
      features, in a limestone cave at the Speleological Province of Bambui (Minas
      Gerais State, Brazil). A total of 8,354 specimens of sandflies belonging to 29
      species were analyzed: Lutzomyia cavernicola (20%), Nyssomyia intermedia (15%),
      Martinsmyia oliveirai (13%), Evandromyia spelunca (12%), Evandromyia sallesi
      (11%), Migonemyia migonei (9%), Nyssomyia whitmani (9%), Sciopemyia sordellii
      (4%) and Lutzomyia longipalpis (2%). The others species represent 5% of the
      total. This manuscript presents data found on richness, diversity, evenness and
      seasonality, comparing the sand fly fauna trapped in the cave and its
      surroundings. 

PMID- 24130848
TI  - Mycoremediation of endosulfan and its metabolites in aqueous medium and soil by
      Botryosphaeria laricina JAS6 and Aspergillus tamarii JAS9.
AB  - Microbial degradation offers an efficient and ecofriendly approach to remove
      toxicants from the contaminated environments. Botryosphaeria laricina JAS6 and
      Aspergillus tamarii JAS9 were capable of degrading endosulfan and their
      metabolites which were isolated through enrichment technique. Both the strains
      were able to withstand an exposure of 1300 mg/L and showed luxuriant growth at
      1000 mg/L of endosulfan. The change in pH in the culture broth was from 6.8 to
      3.4 and 3.8 during growth kinetic studies of JAS6 and JAS9 strains, respectively
      upon biological degradation of endosulfan. The degradation of endosulfan by JAS6
      and JAS9 strains were examined by HPLC. The biodegradation rate constant (k) and
      the initial concentration were reduced by 50% (DT50) which was determined by
      first and pseudo first order kinetic models. In the present investigation it has
      been revealed that Botryosphaeria laricina JAS6 and Aspergillus tamarii JAS9
      possessing endosulfan degrading capability are being reported for the first time.
      These findings confirm the degradation of endosulfan by JAS6 and JAS9 strains
      which were accompanied by significant reduction in the toxicity and could be used
      as remedial measure in contaminated environments. 

PMID- 24130849
TI  - Tbx2a is required for specification of endodermal pouches during development of
      the pharyngeal arches.
AB  - Tbx2 is a member of the T-box family of transcription factors essential for
      embryo- and organogenesis. A deficiency in the zebrafish paralogue tbx2a causes
      abnormalities of the pharyngeal arches in a p53-independent manner. The
      pharyngeal arches are formed by derivatives of all three embryonic germ layers:
      endodermal pouches, mesenchymal condensations and neural crest cells. While tbx2a
      expression is restricted to the endodermal pouches, its function is required for
      the normal morphogenesis of the entire pharyngeal arches. Given the similar
      function of Tbx1 in craniofacial development, we explored the possibility of an
      interaction between Tbx1 and Tbx2a. The use of bimolecular fluorescence
      complementation revealed the interaction between Tbx2a and Tbx1, thus providing
      support for the idea that functional interaction between different, co-expressed
      Tbx proteins could be a common theme across developmental processes in cell
      lineages and tissues. Together, this work provides mechanistic insight into the
      role of TBX2 in human disorders affecting the face and neck. 

PMID- 24130850
TI  - Rapid responses to reverse T3 hormone in immature rat Sertoli cells: calcium
      uptake and exocytosis mediated by integrin.
AB  - There is increasing experimental evidence of the nongenomic action of thyroid
      hormones mediated by receptors located in the plasma membrane or inside cells.
      The aim of this work was to characterize the reverse T3 (rT3) action on calcium
      uptake and its involvement in immature rat Sertoli cell secretion. The results
      presented herein show that very low concentrations of rT3 are able to increase
      calcium uptake after 1 min of exposure. The implication of T-type voltage
      dependent calcium channels and chloride channels in the effect of rT3 was
      evidenced using flunarizine and 9-anthracene, respectively. Also, the rT3-induced
      calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of
      integrin-ligand interactions). Therefore, our findings suggest that calcium
      uptake stimulated by rT3 may be mediated by integrin alphavbeta3. In addition, it
      was demonstrated that calcium uptake stimulated by rT3 is PKC and ERK-dependent.
      Furthermore, the outcomes indicate that rT3 also stimulates cellular secretion
      since the cells manifested a loss of fluorescence after 4 min incubation,
      indicating an exocytic quinacrine release that seems to be mediated by the
      integrin receptor. These findings indicate that rT3 modulates the calcium entry
      and cellular secretion, which might play a role in the regulation of a plethora
      of intracellular processes involved in male reproductive physiology.

PMID- 24130851
TI  - Mosquito consumption by insectivorous bats: does size matter?
AB  - Insectivorous bats have often been touted as biological control for mosquito
      populations. However, mosquitoes generally represent only a small proportion of
      bat diet. Given the small size of mosquitoes, restrictions imposed on prey
      detectability by low frequency echolocation, and variable field metabolic rates
      (FMR), mosquitoes may not be available to or profitable for all bats. This study
      investigated whether consumption of mosquitoes was influenced by bat size, which
      is negatively correlated with echolocation frequency but positively correlated
      with bat FMR. To assess this, we investigated diets of five eastern Australian
      bat species (Vespadelus vulturnus Thomas, V. pumilus Gray, Miniopterus australis
      Tomes, Nyctophilus gouldi Tomes and Chalinolobus gouldii Gray) ranging in size
      from 4-14 g in coastal forest, using molecular analysis of fecal DNA. Abundances
      of potential mosquito and non-mosquito prey were concurrently measured to provide
      data on relative prey abundance. Aedes vigilax was locally the most abundant
      mosquito species, while Lepidoptera the most abundant insect order. A diverse
      range of prey was detected in bat feces, although members of Lepidoptera
      dominated, reflecting relative abundance at trap sites. Consumption of mosquitoes
      was restricted to V. vulturnus and V. pumilus, two smaller sized bats (4 and 4.5
      g). Although mosquitoes were not commonly detected in feces of V. pumilus, they
      were present in feces of 55 % of V. vulturnus individuals. To meet nightly FMR
      requirements, Vespadelus spp. would need to consume ~600-660 mosquitoes on a
      mosquito-only diet, or ~160-180 similar sized moths on a moth-only diet. Lower
      relative profitability of mosquitoes may provide an explanation for the low level
      of mosquito consumption among these bats and the absence of mosquitoes in feces
      of larger bats. Smaller sized bats, especially V. vulturnus, are likely to be
      those most sensitive to reductions in mosquito abundance and should be monitored
      during mosquito control activities. 

PMID- 24130853
TI  - Functional analyses of NSF1 in wine yeast using interconnected correlation
      clustering and molecular analyses.
AB  - Analyzing time-course expression data captured in microarray datasets is a
      complex undertaking as the vast and complex data space is represented by a
      relatively low number of samples as compared to thousands of available genes.
      Here, we developed the Interdependent Correlation Clustering (ICC) method to
      analyze relationships that exist among genes conditioned on the expression of a
      specific target gene in microarray data. Based on Correlation Clustering, the ICC
      method analyzes a large set of correlation values related to gene expression
      profiles extracted from given microarray datasets. ICC can be applied to any
      microarray dataset and any target gene. We applied this method to microarray data
      generated from wine fermentations and selected NSF1, which encodes a C2H2 zinc
      finger-type transcription factor, as the target gene. The validity of the method
      was verified by accurate identifications of the previously known functional roles
      of NSF1. In addition, we identified and verified potential new functions for this
      gene; specifically, NSF1 is a negative regulator for the expression of sulfur
      metabolism genes, the nuclear localization of Nsf1 protein (Nsf1p) is controlled
      in a sulfur-dependent manner, and the transcription of NSF1 is regulated by
      Met4p, an important transcriptional activator of sulfur metabolism genes. The
      inter-disciplinary approach adopted here highlighted the accuracy and relevancy
      of the ICC method in mining for novel gene functions using complex microarray
      datasets with a limited number of samples. 

PMID- 24130852
TI  - Water extract of Ashwagandha leaves has anticancer activity: identification of an
      active component and its mechanism of action.
AB  - BACKGROUND: Cancer is a leading cause of death accounting for 15-20% of global
      mortality. Although advancements in diagnostic and therapeutic technologies have
      improved cancer survival statistics, 75% of the world population live in
      underdeveloped regions and have poor access to the advanced medical remedies.
      Natural therapies hence become an alternative choice of treatment. Ashwagandha, a
      tropical herb used in Indian Ayurvedic medicine, has a long history of its health
      promoting and therapeutic effects. In the present study, we have investigated an
      anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX).
      METHODOLOGY/PRINCIPAL FINDINGS: Anticancer activity in the water extract of
      Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays.
      Bioactivity-based size fractionation and NMR analysis were performed to identify
      the active anticancer component(s). Mechanism of anticancer activity in the
      extract and its purified component was investigated by biochemical assays. We
      report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes
      tumor suppression in vivo. Its active anticancer component was identified as
      triethylene glycol (TEG). Molecular analysis revealed activation of tumor
      suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast
      to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin
      D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal
      cells showed increase in pRB phosphorylation and cyclin B1, and decrease in
      cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3
      and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated
      cancer cells; normal cells remained unaffected. CONCLUSION: We provide the first
      molecular evidence that the ASH-WEX and TEG have selective cancer cell growth
      arrest activity and hence may offer natural and economic resources for anticancer
      medicine.

PMID- 24130854
TI  - 1H NMR spectroscopy profiling of metabolic reprogramming of Chinese hamster ovary
      cells upon a temperature shift during culture.
AB  - We report an NMR based approach to determine the metabolic reprogramming of
      Chinese hamster ovary cells upon a temperature shift during culture by
      investigating the extracellular cell culture media and intracellular metabolome
      of CHOK1 and CHO-S cells during culture and in response to cold-shock and
      subsequent recovery from hypothermic culturing. A total of 24 components were
      identified for CHOK1 and 29 components identified for CHO-S cell systems
      including the observation that CHO-S media contains 5.6 times the level of
      glucose of CHOK1 media at time zero. We confirm that an NMR metabolic approach
      provides quantitative analysis of components such as glucose and alanine with
      both cell lines responding in a similar manner and comparable to previously
      reported data. However, analysis of lactate confirms a differentiation between
      CHOK1 and CHO-S and that reprogramming of metabolism in response to temperature
      was cell line specific. The significance of our results is presented using
      principal component analysis (PCA) that confirms changes in metabolite profile in
      response to temperature and recovery. Ultimately, our approach demonstrates the
      capability of NMR providing real-time analysis to detect reprogramming of
      metabolism upon cellular perception of cold-shock/sub-physiological temperatures.
      This has the potential to allow manipulation of metabolites in culture
      supernatant to improve growth or productivity. 

PMID- 24130855
TI  - Odor uniformity among tomato individuals in response to herbivore depends on
      insect species.
AB  - Plants produce specific volatile organic compound (VOC) blends in response to
      herbivory. Herbivore-induced blends may prime the plant for future attack or
      attract carnivorous insects; these responses have been considered adaptive for
      plants. If herbivores differentially modify the VOC emission among individuals
      within a group of plants they feed upon, then plant responses to herbivores will
      not only produce specific blends but also variation in odor among individuals,
      i.e. individuals smell the same, then having a uniform odor. We investigated the
      VOC emission variation or uniformity among tomato individuals (Solanum
      lycopersicum L. cv. Castlemart) in response to moderate wounding by (1) nymphs of
      the psyllid Bactericera cockerelli (Sulc.) (TP); (2) Lepidoptera chewing-feeding
      larvae of Fall Armyworm (Spodoptera frugiperda Smith) (FAW) and (3) of Cabbage
      Looper (Trichoplusia ni Hubner) (CL), and (4) mechanical damage (MD). We used a
      ratio-based analysis to compare the fold-change in concentration from
      constitutive to induced VOC emission. We also used size and shape analysis to
      compare the emission of damaged and non-damaged individuals. Aside of finding
      herbivore-specific blends in line with other studies, we found patterns not
      described previously. We detected constitutive and induced odor variation among
      individuals attacked by the same herbivore, with the induced odor uniformity
      depending on the herbivore identity. We also showed that the fold-change of VOCs
      from constitutive to induced state differed among individuals independently of
      the uniformity of the blends before herbivore attack. We discuss our findings in
      the context of the ecological roles of VOCs in plant-plant and plant-carnivore
      insects' interactions. 

PMID- 24130856
TI  - CATP-6, a C. elegans ortholog of ATP13A2 PARK9, positively regulates GEM-1, an
      SLC16A transporter.
AB  - In previous work, we found that gain-of-function mutations that hyperactivate GEM
      1 (an SLC16A transporter protein) can bypass the requirement for GON-2 (a TRPM
      channel protein) during the initiation of gonadogenesis in C. elegans.
      Consequently, we proposed that GEM-1 might function as part of a Mg(2+) uptake
      pathway that functions in parallel to GON-2. In this study, we report that CATP
      6, a C. elegans ortholog of the P5B ATPase, ATP13A2 (PARK9), is necessary for gem
      1 gain-of-function mutations to suppress the effects of gon-2 inactivation. One
      possible explanation for this observation is that GEM-1 serves to activate CATP
      6, which then functions as a Mg(2+) transporter. However, we found that
      overexpression of GEM-1 can alleviate the requirement for CATP-6 activity,
      suggesting that CATP-6 probably acts as a non-essential upstream positive
      regulator of GEM-1. Our results are consistent with the notion that P5B ATPases
      govern intracellular levels of Mg(2+) and/or Mn(2+) by regulating the trafficking
      of transporters and other proteins associated with the plasma membrane. 

PMID- 24130857
TI  - Cytokine profiles at birth predict malaria severity during infancy.
AB  - BACKGROUND: Severe malaria risk varies between individuals, and most of this
      variation remains unexplained. Here, we examined the hypothesis that cytokine
      profiles at birth reflect inter-individual differences that persist and influence
      malaria parasite density and disease severity throughout early childhood. METHODS
      AND FINDINGS: Cytokine levels (TNF-alpha, IFN-gamma, IL-1beta, IL-4, IL-5, IL-6
      and IL-10) were measured at birth (cord blood; N=783) and during subsequent
      routine follow-up visits (peripheral blood) for children enrolled between 2002
      and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear
      and clinical assessments every 2-4 weeks, and at the time of any illness. Cord
      blood levels of all cytokines were positively correlated with each other
      (Spearman's rank correlation). Cord levels of IL-1beta and TNF-alpha (but not
      other cytokines) correlated with levels of the same cytokine measured at routine
      visits during early life (P < 0.05). Higher cord levels of IL-1beta but not TNF
      alpha were associated with lower parasite densities during infancy (P=0.003;
      Generalized Estimating Equation (GEE) method), with an average ~40% reduction
      versus children with low cord IL-1beta levels, and with decreased risk of severe
      malaria during follow-up (Cox regression): adjusted hazard ratio (95% CI) 0.60
      (0.39-0.92), P = 0.02. CONCLUSION: IL-1beta levels at birth are related to future
      IL-1beta levels as well as the risk of severe malaria in early life. The effect
      on severe malaria risk may be due in part to the effect of inflammatory cytokines
      to control parasite density.

PMID- 24130858
TI  - The association between intelligence scores and family history of psychiatric
      disorder in schizophrenia patients, their siblings and healthy controls.
AB  - BACKGROUND: The degree of intellectual impairment in schizophrenia patients and
      their relatives has been suggested to be associated with the degree of familial
      loading for schizophrenia. Since other psychiatric disorders are also more
      present in relatives of schizophrenia patients, the definition of family history
      should be broadened. The association between family history for psychiatric
      disorder and intelligence scores was investigated in patients with non-affective
      psychosis, their unaffected siblings and controls. METHODS: A sample of 712
      schizophrenia proband families (696 patients and 766 siblings) and 427 healthy
      control families (517 subjects) participated in this study. Family history of
      psychiatric disorder was determined while excluding the data of the participating
      schizophrenia patient. A dichotomous division was made between families with no
      first- or second degree relative with psychiatric disorder and families with one
      or more affected relatives. Total intelligence scores were estimated by admission
      of the short form of the Wechsler Adult Intelligence Scale III. RESULTS: A
      significant interaction was found between family history of psychiatric disorder
      and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family
      history of psychiatric disorder obtained higher intelligence scores compared to
      patients with no family history (mean IQ scores are 95.52 and 92.72) with an
      opposite effect in controls (mean IQ scores are 108.71 and 111.19). No
      significant difference was found between siblings of schizophrenia patients with
      or without a positive family history (mean IQ scores are 102.98 and 103.24).
      CONCLUSION: In patients with schizophrenia, a negative family history of
      psychiatric disorder was associated with relatively low IQ suggesting that the
      etiology in these patients may involve environmental or genetic factors which are
      unique to the patient and are not observed in other relatives. Possible factors
      include severe environmental stressors containing premature birth or brain injury
      and genetic factors (e.g de novo Copy Number Variants).

PMID- 24130860
TI  - Performance of SAPS II and SAPS 3 in intermediate care.
AB  - OBJECTIVE: The efficacy and reliability of prognostic scores has been described
      extensively for intensive care, but their role for predicting mortality in
      intermediate care patients is uncertain. To provide more information in this
      field, we have analyzed the performance of the Simplified Acute Physiology Score
      (SAPS) II and SAPS 3 in a single center intermediate care unit (ImCU). MATERIALS
      AND METHODS: Cohort study with prospectively collected data from all patients
      admitted to a single center ImCU in Pamplona, Spain, from April 2006 to April
      2012. The SAPS II and SAPS 3 scores with respective predicted mortality rates
      were calculated according to standard coefficients. Discrimination was evaluated
      by calculating the area under receiver operating characteristic curve (AUROC) and
      calibration with the Hosmer-Lemeshow goodness of fit test. Standardized mortality
      ratios (SMR) with 95% confidence interval (95% CI) were calculated for each
      model. RESULTS: The study included 607 patients. The observed in-hospital
      mortality was 20.1% resulting in a SMR of 0.87 (95% CI 0.73-1.04) for SAPS II and
      0.56 (95% CI 0.47-0.67) for SAPS 3. Both scores showed acceptable discrimination,
      with an AUROC of 0.76 (95% CI 0.71-0.80) for SAPS II and 0.75 (95% CI 0.71- 0.80)
      for SAPS 3. Calibration curves showed similar performance based on Hosmer
      Lemeshow goodness of fit C-test: (X(2)=12.9, p=0.113) for SAPS II and (X(2)=4.07,
      p=0.851) for SAPS 3. CONCLUSIONS: Although both scores overpredicted mortality,
      SAPS II showed better discrimination for patients admitted to ImCU in terms of
      SMR.

PMID- 24130859
TI  - Transcriptomic analysis of Paulownia infected by Paulownia witches'-broom
      Phytoplasma.
AB  - Phytoplasmas are plant pathogenic bacteria that have no cell wall and are
      responsible for major crop losses throughout the world. Phytoplasma-infected
      plants show a variety of symptoms and the mechanisms they use to physiologically
      alter the host plants are of considerable interest, but poorly understood. In
      this study we undertook a detailed analysis of Paulownia infected by Paulownia
      witches'-broom (PaWB) Phytoplasma using high-throughput mRNA sequencing (RNA-Seq)
      and digital gene expression (DGE). RNA-Seq analysis identified 74,831 unigenes,
      which were subsequently used as reference sequences for DGE analysis of diseased
      and healthy Paulownia in field grown and tissue cultured plants. Our study
      revealed that dramatic changes occurred in the gene expression profile of
      Paulownia after PaWB Phytoplasma infection. Genes encoding key enzymes in
      cytokinin biosynthesis, such as isopentenyl diphosphate isomerase and
      isopentenyltransferase, were significantly induced in the infected Paulownia.
      Genes involved in cell wall biosynthesis and degradation were largely up
      regulated and genes related to photosynthesis were down-regulated after PaWB
      Phytoplasma infection. Our systematic analysis provides comprehensive
      transcriptomic data about plants infected by Phytoplasma. This information will
      help further our understanding of the detailed interaction mechanisms between
      plants and Phytoplasma. 

PMID- 24130861
TI  - An intriguing shift occurs in the novel protein phosphatase 1 binding partner,
      TCTEX1D4: evidence of positive selection in a pika model.
AB  - T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) contains the
      canonical phosphoprotein phosphatase 1 (PPP1) binding motif, composed by the
      amino acid sequence RVSF. We identified and validated the binding of TCTEX1D4 to
      PPP1 and demonstrated that indeed this protein is a novel PPP1 interacting
      protein. Analyses of twenty-one mammalian species available in public databases
      and seven Lagomorpha sequences obtained in this work showed that the PPP1 binding
      motif 90RVSF93 is present in all of them and is flanked by a palindromic
      sequence, PLGS, except in three species of pikas (Ochotona princeps, O. dauurica
      and O. pusilla). Furthermore, for the Ochotona species an extra glycosylation
      site, motif 96NLS98, and the loss of the palindromic sequence were observed.
      Comparison with other lagomorphs suggests that this event happened before the
      Ochotona radiation. The dN/dS for the sequence region comprising the PPP1 binding
      motif and the flanking palindrome highly supports the hypothesis that for
      Ochotona species this region has been evolving under positive selection. In
      addition, mutational screening shows that the ability of pikas TCTEX1D4 to bind
      to PPP1 is maintained, although the PPP1 binding motif is disrupted, and the N-
      and C-terminal surrounding residues are also abrogated. These observations
      suggest pika as an ideal model to study novel PPP1 complexes regulatory
      mechanisms. 

PMID- 24130862
TI  - Protective immunity against Trichinella spiralis infection induced by a multi
      epitope vaccine in a murine model.
AB  - Trichinellosis is one of the most important food-borne parasitic zoonoses
      throughout the world. Because infected pigs are the major source of human
      infections, and China is becoming the largest international producer of pork, the
      development of a transmission-blocking vaccine to prevent swine from being
      infected is urgently needed for trichinellosis control in China. Our previous
      studies have demonstrated that specific Trichinella spiralis paramyosin (Ts-Pmy)
      and Ts-87 antigen could provide protective immunity against T. spiralis infection
      in immunized mice. Certain protective epitopes of Ts-Pmy and Ts-87 antigen have
      been identified. To identify more Ts-Pmy protective epitopes, a new monoclonal
      antibody, termed 8F12, was produced against the N-terminus of Ts-Pmy. This
      antibody elicited significant protective immunity in mice against T. spiralis
      infection by passive transfer and was subsequently used to screen a random phage
      display peptide library to identify recognized epitopes. Seven distinct positive
      phage clones were identified and their displayed peptides were sequenced.
      Synthesized epitope peptides conjugated to keyhole limpet hemocyanin were used to
      immunize mice, four of which exhibited larval reduction (from 18.7% to 26.3%,
      respectively) in vaccinated mice in comparison to the KLH control. To increase
      more effective protection, the epitope 8F7 that was found to induce the highest
      protection in this study was combined with two other previously identified
      epitopes (YX1 from Ts-Pmy and M7 from Ts-87) to formulate a multi-epitope
      vaccine. Mice immunized with this multi-epitope vaccine experienced a 35.0%
      reduction in muscle larvae burden after being challenged with T. spiralis larvae.
      This protection is significantly higher than that induced by individual-epitope
      peptides and is associated with high levels of subclasses IgG and IgG1. These
      results showed that a multi-epitope vaccine induced better protective immunity
      than an individual epitope and provided a feasible approach for developing a
      safer and more effective vaccine against trichinellosis. 

PMID- 24130863
TI  - Enhancement of carbon sequestration in soil in the temperature grasslands of
      northern China by addition of nitrogen and phosphorus.
AB  - Increased nitrogen (N) deposition is common worldwide. Questions of where, how,
      and if reactive N-input influences soil carbon (C) sequestration in terrestrial
      ecosystems are of great concern. To explore the potential for soil C
      sequestration in steppe region under N and phosphorus (P) addition, we conducted
      a field experiment between 2006 and 2012 in the temperate grasslands of northern
      China. The experiment examined 6 levels of N (0-56 g N m(-2) yr(-1)), 6 levels of
      P (0-12.4 g P m(-2) yr(-1)), and a control scenario. Our results showed that
      addition of both N and P enhanced soil total C storage in grasslands due to
      significant increases of C input from litter and roots. Compared with control
      plots, soil organic carbon (SOC) in the 0-100 cm soil layer varied quadratically,
      from 156.8 to 1352.9 g C m(-2) with N addition gradient (R(2) = 0.99, P < 0.001);
      and logarithmically, from 293.6 to 788.6 g C m(-2) with P addition gradient (R(2)
      = 0.56, P = 0.087). Soil inorganic carbon (SIC) decreased quadratically with N
      addition. The net C sequestration on grassland (including plant, roots, SIC, and
      SOC) increased linearly from -128.6 to 729.0 g C m(-2) under N addition (R(2) =
      0.72, P = 0.023); and increased logarithmically, from 248.5 to 698 g C m(-2)under
      P addition (R(2) = 0.82, P = 0.014). Our study implies that N addition has
      complex effects on soil carbon dynamics, and future studies of soil C
      sequestration on grasslands should include evaluations of both SOC and SIC under
      various scenarios. 

PMID- 24130864
TI  - Synergistic effects of concurrent blockade of PI3K and MEK pathways in pancreatic
      cancer preclinical models.
AB  - Patients with pancreatic cancer have dismal prognoses, and novel therapies are
      urgently needed. Mutations of the KRAS oncogene occur frequently in pancreatic
      cancer and represent an attractive target. Direct targeting of the predominant
      KRAS pathways have been challenging and research into therapeutic strategies have
      been now refocused on pathways downstream of KRAS, phosphoinositide 3-kinase
      (PI3K) and mitogen-activated protein kinase (MAPK [MEK]). We hypothesized that
      concurrent inhibition of the PI3K and MEK pathways would result in synergistic
      antitumor activity, as it would circumvent the compensatory feedback loop between
      the two pathways. We investigated the combined effect of the PI3K inhibitor,
      GDC0941, and the MEK inhibitor, AZD6244, on cell viability, apoptosis and cell
      signaling in a panel of pancreatic cancer cell lines. An in vivo analysis was
      conducted on pancreatic cancer xenografts. While BxPC-3 (KRAS wild type) and MIA
      PaCa-2 (KRAS mutated) cell lines were sensitive to GDC0941 and AZD6244 as single
      agents, synergistic inhibition of tumor cell growth and induction of apoptosis
      were observed in both cell lines when the two drugs were combined. Interestingly,
      phosphorylation of the cap-dependent translational components, 4E-binding protein
      (p-4E-BP1) and S6 was found to be closely associated with sensitivity to GDC0941
      and AZD6244. In BxPC-3 cell xenografts, survival differences were observed
      between the control and the AZD6244, GDC0941, and combination groups. Our study
      provides the rationale for concurrent targeting of the PI3K and MEK pathways,
      regardless of KRAS status, and suggests that phosphorylation of 4E-BP1and S6 can
      serve as a predictive biomarker for response to treatment. 

PMID- 24130865
TI  - At-risk elementary school children with one year of classroom music instruction
      are better at keeping a beat.
AB  - Temporal processing underlies both music and language skills. There is increasing
      evidence that rhythm abilities track with reading performance and that language
      disorders such as dyslexia are associated with poor rhythm abilities. However,
      little is known about how basic time-keeping skills can be shaped by musical
      training, particularly during critical literacy development years. This study was
      carried out in collaboration with Harmony Project, a non-profit organization
      providing free music education to children in the gang reduction zones of Los
      Angeles. Our findings reveal that elementary school children with just one year
      of classroom music instruction perform more accurately in a basic finger-tapping
      task than their untrained peers, providing important evidence that fundamental
      time-keeping skills may be strengthened by short-term music training. This sets
      the stage for further examination of how music programs may be used to support
      the development of basic skills underlying learning and literacy, particularly in
      at-risk populations which may benefit the most. 

PMID- 24130866
TI  - Large extent of disorder in Adenomatous Polyposis Coli offers a strategy to guard
      Wnt signalling against point mutations.
AB  - Mutations in the central region of the signalling hub Adenomatous Polyposis Coli
      (APC) cause colorectal tumourigenesis. The structure of this region remained
      unknown. Here, we characterise the Mutation Cluster Region in APC (APC-MCR) as
      intrinsically disordered and propose a model how this structural feature may
      contribute to regulation of Wnt signalling by phosphorylation. APC-MCR was
      susceptible to proteolysis, lacked alpha-helical secondary structure and did not
      display thermal unfolding transition. It displayed an extended conformation in
      size exclusion chromatography and was accessible for phosphorylation by
      CK1epsilon in vitro. The length of disordered regions in APC increases with
      species complexity, from C. elegans to H. sapiens. We speculate that the large
      disordered region harbouring phosphorylation sites could be a successful strategy
      to stabilise tight regulation of Wnt signalling against single missense
      mutations. 

PMID- 24130867
TI  - Podoplanin immunopositive lymphatic vessels at the implant interface in a rat
      model of osteoporotic fractures.
AB  - Insertion of bone substitution materials accelerates healing of osteoporotic
      fractures. Biodegradable materials are preferred for application in osteoporotic
      patients to avoid a second surgery for implant replacement. Degraded implant
      fragments are often absorbed by macrophages that are removed from the fracture
      side via passage through veins or lymphatic vessels. We investigated if lymphatic
      vessels occur in osteoporotic bone defects and whether they are regulated by the
      use of different materials. To address this issue osteoporosis was induced in
      rats using the classical method of bilateral ovariectomy and additional calcium
      and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm
      were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm
      defects were subsequently used for implantation studies where bone substitution
      materials of calcium phosphate cement, composites of collagen and silica, and
      iron foams with interconnecting pores were inserted. Different materials were
      partly additionally functionalized by strontium or bisphosphonate whose positive
      effects in osteoporosis treatment are well known. The lymphatic vessels were
      identified by immunohistochemistry using an antibody against podoplanin.
      Podoplanin immunopositive lymphatic vessels were detected in the granulation
      tissue filling the fracture gap, surrounding the implant and growing into the
      iron foam through its interconnected pores. Significant more lymphatic
      capillaries were counted at the implant interface of composite, strontium and
      bisphosphonate functionalized iron foam. A significant increase was also observed
      in the number of lymphatics situated in the pores of strontium coated iron foam.
      In conclusion, our results indicate the occurrence of lymphatic vessels in
      osteoporotic bone. Our results show that lymphatic vessels are localized at the
      implant interface and in the fracture gap where they might be involved in the
      removal of lymphocytes, macrophages, debris and the implants degradation
      products. Therefore the lymphatic vessels are involved in implant integration and
      fracture healing. 

PMID- 24130868
TI  - Genes and co-expression modules common to drought and bacterial stress responses
      in Arabidopsis and rice.
AB  - Plants are simultaneously exposed to multiple stresses resulting in enormous
      changes in the molecular landscape within the cell. Identification and
      characterization of the synergistic and antagonistic components of stress
      response mechanisms contributing to the cross talk between stresses is of high
      priority to explore and enhance multiple stress responses. To this end, we
      performed meta-analysis of drought (abiotic), bacterial (biotic) stress response
      in rice and Arabidopsis by analyzing a total of 386 microarray samples belonging
      to 20 microarray studies and identified approximately 3100 and 900 DEGs in rice
      and Arabidopsis, respectively. About 38.5% (1214) and 28.7% (272) DEGs were
      common to drought and bacterial stresses in rice and Arabidopsis, respectively. A
      majority of these common DEGs showed conserved expression status in both
      stresses. Gene ontology enrichment analysis clearly demarcated the response and
      regulation of various plant hormones and related biological processes. Fatty acid
      metabolism and biosynthesis of alkaloids were upregulated and, nitrogen
      metabolism and photosynthesis was downregulated in both stress conditions. WRKY
      transcription family genes were highly enriched in all upregulated gene sets
      while 'CO-like' TF family showed inverse relationship of expression between
      drought and bacterial stresses. Weighted gene co-expression network analysis
      divided DEG sets into multiple modules that show high co-expression and
      identified stress specific hub genes with high connectivity. Detection of
      consensus modules based on DEGs common to drought and bacterial stress revealed 9
      and 4 modules in rice and Arabidopsis, respectively, with conserved and reversed
      co-expression patterns. 

PMID- 24130870
TI  - Analysis of balance, rapidity, force and reaction times of soccer players at
      different levels of competition.
AB  - In the present study we analyzed 12 physical parameters, namely force, static and
      dynamic balance (both quantified by means of 4 parameters each), rapidity, visual
      reaction times and acoustic reaction times, over 185 subjects. 170 of them played
      soccer in teams enrolled in all the ten different Italian soccer leagues. Results
      show that 6 parameters (out of the 12 analyzed) permit to identify and
      discriminate top-level players, among those showing the same training frequency.
      The other parameters are strictly related to training frequency or do not
      discriminate among players or control subjects (non-athletes), such as visual and
      acoustic reaction times. Principal component analysis permits to identify 4
      clusters of subjects with similar performances, thus representing a useful
      instrument to characterize the overall ability of players in terms of athletic
      characteristics, on the basis of their location on the principal component
      parameters plane. 

PMID- 24130869
TI  - Non-specific dsRNA-mediated antiviral response in the honey bee.
AB  - Honey bees are essential pollinators of numerous agricultural crops. Since 2006,
      honey bee populations have suffered considerable annual losses that are partially
      attributed to Colony Collapse Disorder (CCD). CCD is an unexplained phenomenon
      that correlates with elevated incidence of pathogens, including RNA viruses.
      Honey bees are eusocial insects that live in colonies of genetically related
      individuals that work in concert to gather and store nutrients. Their social
      organization provides numerous benefits, but also facilitates pathogen
      transmission between individuals. To investigate honey bee antiviral defense
      mechanisms, we developed an RNA virus infection model and discovered that
      administration of dsRNA, regardless of sequence, reduced virus infection. Our
      results suggest that dsRNA, a viral pathogen associated molecular pattern (PAMP),
      triggers an antiviral response that controls virus infection in honey bees. 

PMID- 24130871
TI  - Ritonavir-boosted darunavir is rarely associated with nephrolithiasis compared
      with ritonavir-boosted atazanavir in HIV-infected patients.
AB  - BACKGROUND: Although ritonavir-boosted atazanavir (ATV/r) is known to be
      associated with nephrolithiasis, little is known about the incidence of
      nephrolithiasis in patients treated with ritonavir-boosted Darunavir (DRV/r), the
      other preferred protease inhibitor. METHODS: In a single-center cohort, the
      incidence of nephrolithiasis was compared between HIV-infected patients who
      commenced DRV/r-containing antiretroviral therapy and those on ATV/r. The effects
      of ATV/r use over DRV/r were estimated by univariate and multivariate Cox hazards
      models. RESULTS: Renal stones were diagnosed in only one patient (0.86 per 1000
      person-years) of the DRV/r group (n=540) and 37 (20.2 per 1000 person-years) of
      the ATV/r group (n=517). The median [interquartile (IQR)] observation period in
      the DRV/r group was 27.1 months (IQR 18.1-38.4 months), and 40.6 months (IQR 17.5
      42.7) for the ATV/r group. The total observation period was 1,163.6 person-years
      and 1,829.6 person-years for the DRV/r group and for the ATV/r group,
      respectively. In the 37 patients on ATV/r who developed nephrolithiasis, the
      median time from commencement of ATV/r to diagnosis was 28.1 months (IQR 18.4
      42.7), whereas nephrolithiasis in the single patient of the DRV/r group occurred
      11.2 month after the introduction of DRV/r. ATV/r use over DRV/r was
      significantly associated with nephrolithiasis by uni- and multivariate analyses
      (HR=26.01; 95% CI, 3.541-191.0; p=0.001) (adjusted HR=21.47; 95% CI, 2.879-160.2;
      p=0.003). CONCLUSION: The incidence of nephrolithiasis was substantially lower in
      patients on DRV/r than those on ATV/r. The results suggest that DRV/r should be
      selected for treatment of HIV-infected patients at risk of chronic kidney
      disease.

PMID- 24130872
TI  - Impact of functional constipation on health-related quality of life in preschool
      children and their families in Xi'an, China.
AB  - AIM: Functional constipation (FC) is one of the common diseases among children.
      The aim of this study was to investigate the health-related quality of life
      (HRQOL) in preschool children diagnosed with FC and the impact of the condition
      on affected families. METHODS: In this cross-sectional, case-control study, 152
      children aged 3-6 years with FC, 176 healthy children aged 3-6 years without FC,
      and their primary caregivers were selected. Chinese versions of the PedsQLTM 4.0
      Generic Core Scale and the Family Impact Module (FIM) were used to assess
      childhood HRQOL and the impact of FC on family members, respectively. HRQOL
      scores were compared between children with FC and healthy children. In addition,
      a multiple step-wise regression with demographic variables of children and their
      caregivers, family economic status, duration and symptoms of FC, as independent
      variables, was used to determine factors that influenced HRQOL in children and
      had impacted caregivers. RESULTS: Scores of physical, emotional, social and
      school functions, and summary scales were significantly lower in children with FC
      than in healthy children (p < 0.05). Physical, emotional, social, cognitive, and
      communication scores for caregivers, as well as daily activities and
      relationships for families of children with FC, were significantly lower than
      those of caregivers and families with healthy children (p < 0.05). Children's
      ages, duration of FC, symptoms of FC, the child-caregiver relationship, family
      economic status, and caregiver education level emerged as the main factors
      influencing HRQOL in children, caregivers, and family members. CONCLUSIONS: FC
      had a significant impact on HRQOL of affected children and their caregivers, as
      well as their family functions. Social characteristics of children and
      caregivers, duration and symptoms of FC and family economic status significantly
      affected HRQOL of children and caregivers, as well as family functions of
      children with FC.

PMID- 24130873
TI  - Co-culture with Listeria monocytogenes within a dual-species biofilm community
      strongly increases resistance of Pseudomonas putida to benzalkonium chloride.
AB  - Biofilm formation is a phenomenon occurring almost wherever microorganisms and
      surfaces exist in close proximity. This study aimed to evaluate the possible
      influence of bacterial interactions on the ability of Listeria monocytogenes and
      Pseudomonas putida to develop a dual-species biofilm community on stainless steel
      (SS), as well as on the subsequent resistance of their sessile cells to
      benzalkonium chloride (BC) used in inadequate (sub-lethal) concentration (50
      ppm). The possible progressive adaptability of mixed-culture biofilms to BC was
      also investigated. To accomplish these, 3 strains per species were left to
      develop mixed-culture biofilms on SS coupons, incubated in daily renewable growth
      medium for a total period of 10 days, under either mono- or dual-species
      conditions. Each day, biofilm cells were exposed to disinfection treatment.
      Results revealed that the simultaneous presence of L. monocytogenes strongly
      increased the resistance of P. putida biofilm cells to BC, while culture
      conditions (mono-/dual-species) did not seem to significantly influence the
      resistance of L. monocytogenes biofilm cells. BC mainly killed L. monocytogenes
      cells when this was applied against the dual-species sessile community during the
      whole incubation period, despite the fact that from the 2nd day this community
      was mainly composed (>90%) of P. putida cells. No obvious adaptation to BC was
      observed in either L. monocytogenes or P. putida biofilm cells. Pulsed field gel
      electrophoresis (PFGE) analysis showed that the different strains behaved
      differently with regard to biofilm formation and antimicrobial resistance. Such
      knowledge on the physiological behavior of mixed-culture biofilms could provide
      the information necessary to control their formation. 

PMID- 24130874
TI  - Thioredoxin is involved in endothelial cell extracellular transglutaminase 2
      activation mediated by celiac disease patient IgA.
AB  - PURPOSE: To investigate the role of thioredoxin (TRX), a novel regulator of
      extracellular transglutaminase 2 (TG2), in celiac patients IgA (CD IgA) mediated
      TG2 enzymatic activation. METHODS: TG2 enzymatic activity was evaluated in
      endothelial cells (HUVECs) under different experimental conditions by ELISA and
      Western blotting. Extracellular TG2 expression was studied by ELISA and
      immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum
      immunoglobulins class A from healthy subjects (H IgA) were used as controls.
      Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX
      inhibitor, was also employed in the present study. RESULTS: We have found that in
      HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose
      dependent manner. Particularly, we noted that the extracellular modulation of TG2
      activity mediated by CD IgA occurred only under reducing conditions, also needed
      to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were
      characterized by a slightly augmented TG2 surface expression which was
      independent from extracellular TG2 activation. We also observed that HUVECs
      cultured in the presence of CD IgA evinced decreased TRX surface expression,
      coupled with increased secretion of the protein into the culture medium.
      Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most
      of the CD IgA-mediated effects including the TG2 extracellular transamidase
      activity. CONCLUSIONS: Altogether our findings suggest that in endothelial cells
      CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism
      involving the redox sensor protein TRX.

PMID- 24130875
TI  - Functional evolution of a multigene family: orthologous and paralogous pheromone
      receptor genes in the turnip moth, Agrotis segetum.
AB  - Lepidopteran pheromone receptors (PRs), for which orthologies are evident among
      closely related species, provide an intriguing example of gene family evolution
      in terms of how new functions may arise. However, only a limited number of PRs
      have been functionally characterized so far and thus evolutionary scenarios
      suffer from elements of speculation. In this study we investigated the turnip
      moth Agrotis segetum, in which female moths produce a mixture of chemically
      related pheromone components that elicit specific responses from receptor cells
      on male antennae. We cloned nine A. segetum PR genes and the Orco gene by
      degenerate primer based RT-PCR. The nine PR genes, named as AsegOR1 and AsegOR3
      10, fall into four distinct orthologous clusters of known lepidopteran PRs, of
      which one contains six paralogues. The paralogues are under relaxed selective
      pressure, contrasting with the purifying selection on other clusters. We
      identified the receptors AsegOR9, AsegOR4 and AsegOR5, specific for the
      respective homologous pheromone components (Z)-5-decenyl, (Z)-7-dodecenyl and (Z)
      9-tetradecenyl acetates, by two-electrode voltage clamp recording from Xenopus
      laevis oocytes co-expressing Orco and each PR candidate. These receptors occur in
      three different orthologous clusters. We also found that the six paralogues with
      high sequence similarity vary dramatically in ligand selectivity and sensitivity.
      Different from AsegOR9, AsegOR6 showed a relatively large response to the
      behavioural antagonist (Z)-5-decenol, and a small response to (Z)-5-decenyl
      acetate. AsegOR1 was broadly tuned, but most responsive to (Z)-5-decenyl acetate,
      (Z)-7-dodecenyl acetate and the behavioural antagonist (Z)-8-dodecenyl acetate.
      AsegOR8 and AsegOR7, which differ from AsegOR6 and AsegOR1 by 7 and 10 aa
      respectively, showed much lower sensitivities. AsegOR10 showed only small
      responses to all the tested compounds. These results suggest that new receptors
      arise through gene duplication, and relaxed evolutionary constraints or positive
      selection among paralogues allow functional divergence to occur in spite of
      purifying selection being the norm. 

PMID- 24130876
TI  - Viral infection affects sucrose responsiveness and homing ability of forager
      honey bees, Apis mellifera L.
AB  - Honey bee health is mainly affected by Varroa destructor, viruses, Nosema spp.,
      pesticide residues and poor nutrition. Interactions between these proposed
      factors may be responsible for the colony losses reported worldwide in recent
      years. In the present study, the effects of a honey bee virus, Israeli acute
      paralysis virus (IAPV), on the foraging behaviors and homing ability of European
      honey bees (Apis mellifera L.) were investigated based on proboscis extension
      response (PER) assays and radio frequency identification (RFID) systems. The
      pollen forager honey bees originated from colonies that had no detectable level
      of honey bee viruses and were manually inoculated with IAPV to induce the viral
      infection. The results showed that IAPV-inoculated honey bees were more
      responsive to low sucrose solutions compared to that of non-infected foragers.
      After two days of infection, around 107 copies of IAPV were detected in the heads
      of these honey bees. The homing ability of IAPV-infected foragers was depressed
      significantly in comparison to the homing ability of uninfected foragers. The
      data provided evidence that IAPV infection in the heads may enable the virus to
      disorder foraging roles of honey bees and to interfere with brain functions that
      are responsible for learning, navigation, and orientation in the honey bees,
      thus, making honey bees have a lower response threshold to sucrose and lose their
      way back to the hive.

PMID- 24130877
TI  - Ten years after the prestige oil spill: seabird trophic ecology as indicator of
      long-term effects on the coastal marine ecosystem.
AB  - Major oil spills can have long-term impacts since oil pollution does not only
      result in acute mortality of marine organisms, but also affects productivity
      levels, predator-prey dynamics, and damages habitats that support marine
      communities. However, despite the conservation implications of oil accidents, the
      monitoring and assessment of its lasting impacts still remains a difficult and
      daunting task. Here, we used European shags to evaluate the overall, lasting
      effects of the Prestige oil spill (2002) on the affected marine ecosystem. Using
      delta 15N and Hg analysis, we trace temporal changes in feeding ecology
      potentially related to alterations of the food web due to the spill. Using
      climatic and oceanic data, we also investigate the influence of North Atlantic
      Oscillation (NAO) index, the sea surface temperature (SST) and the chlorophyll a
      (Chl a) on the observed changes. Analysis of delta 15N and Hg concentrations
      revealed that after the Prestige oil spill, shag chicks abruptly switched their
      trophic level from a diet based on a high percentage of demersal-benthic fish to
      a higher proportion of pelagic/semi-pelagic species. There was no evidence that
      Chl a, SST and NAO reflected any particular changes or severity in environmental
      conditions for any year or season that may explain the sudden change observed in
      trophic level. Thus, this study highlighted an impact on the marine food web for
      at least three years. Our results provide the best evidence to date of the long
      term consequences of the Prestige oil spill. They also show how, regardless of
      wider oceanographic variability, lasting impacts on predator-prey dynamics can be
      assessed using biochemical markers. This is particularly useful if larger scale
      and longer term monitoring of all trophic levels is unfeasible due to limited
      funding or high ecosystem complexity.

PMID- 24130878
TI  - Direct interaction between AR and PAK6 in androgen-stimulated PAK6 activation.
AB  - A p21-activated kinase 6 (PAK6) was previously identified to be an androgen
      receptor (AR) interacting protein through a yeast two-hybrid screening. We used
      hormone responsive prostate cancer LAPC4 and LNCap cell lines as models to study
      the signaling events associated with androgen stimulation and PAK6. An androgen
      stimulated PAK6 kinase activation was observed in LAPC4 cells expressing
      endogenous PAK6 and in LNCap cells ectopically expressing a wild type PAK6. This
      activation was likely mediated through a direct interaction between AR and PAK6
      since siRNA knock-down of AR in LAPC4 cells downregulated androgen-stimulated
      PAK6 activation. In addition, LNCap cells expressing a non-AR-interacting PAK6
      mutant exhibited dampened androgen-stimulated kinase activation. As a consequence
      of androgen-stimulated activation, PAK6 was phosphorylated at multiple
      serine/threonine residues including the AR-interacting domain of PAK6.
      Furthermore, androgen-stimulation promoted prostate cancer cell motility and
      invasion were demonstrated in LNCap cells ectopically expressing PAK6-WT. In
      contrast, LNCap expressing non-AR-interacting mutant PAK6 did not respond to
      androgen stimulation with increased cell motility and invasion. Our results
      demonstrate that androgen-stimulated PAK6 activation is mediated through a direct
      interaction between AR and PAK6 and PAK6 activation promotes prostate cancer
      cells motility and invasion. 

PMID- 24130879
TI  - Disentangling coordination among functional traits using an individual-centred
      model: impact on plant performance at intra- and inter-specific levels.
AB  - BACKGROUND: Plant functional traits co-vary along strategy spectra, thereby
      defining trade-offs for resource acquisition and utilization amongst other
      processes. A main objective of plant ecology is to quantify the correlations
      among traits and ask why some of them are sufficiently closely coordinated to
      form a single axis of functional specialization. However, due to trait co
      variations in nature, it is difficult to propose a mechanistic and causal
      explanation for the origin of trade-offs among traits observed at both intra- and
      inter-specific level. METHODOLOGY/PRINCIPAL FINDINGS: Using the G(EMINI)
      individual-centered model which coordinates physiological and morphological
      processes, we investigated with 12 grass species the consequences of deliberately
      decoupling variation of leaf traits (specific leaf area, leaf lifespan) and plant
      stature (height and tiller number) on plant growth and phenotypic variability.
      For all species under both high and low N supplies, simulated trait values
      maximizing plant growth in monocultures matched observed trait values. Moreover,
      at the intraspecific level, plastic trait responses to N addition predicted by
      the model were in close agreement with observed trait responses. In a 4D trait
      space, our modeling approach highlighted that the unique trait combination
      maximizing plant growth under a given environmental condition was determined by a
      coordination of leaf, root and whole plant processes that tended to co-limit the
      acquisition and use of carbon and of nitrogen. CONCLUSION/SIGNIFICANCE: Our study
      provides a mechanistic explanation for the origin of trade-offs between plant
      functional traits and further predicts plasticity in plant traits in response to
      environmental changes. In a multidimensional trait space, regions occupied by
      current plant species can therefore be viewed as adaptive corridors where trait
      combinations minimize allometric and physiological constraints from the organ to
      the whole plant levels. The regions outside this corridor are empty because of
      inferior plant performance.

PMID- 24130880
TI  - Targeting c-MYC with T-cells.
AB  - Over-expression of the proto-oncogene c-MYC is frequently observed in a variety
      of tumors and is a hallmark of Burkitt's lymphoma. The fact that many tumors are
      oncogene-addicted to c-MYC, renders c-MYC a powerful target for anti-tumor
      therapy. Using a xenogenic vaccination strategy by immunizing C57BL/6 mice with
      human c-MYC protein or non-homologous peptides, we show that the human c-MYC
      protein, despite its high homology between mouse and man, contains several
      immunogenic epitopes presented in the context of murine H2(b) haplotype. We
      identified an MHC class II-restricted CD4+ T-cell epitope and therein an MHC
      class I-restricted CD8+ T-cell epitope (SSPQGSPEPL) that, after prime/boost
      immunization, protected up to 25% of mice against a lethal lymphoma challenge.
      Lymphoma-rejecting animals contained MHC multimer-binding CD8+ cell within the
      peripheral blood and displayed in vivo cytolytic activity with specificity for
      SSPQGSPEPL. Taken together these data suggest that oncogenic c-MYC can be
      targeted with specific T-cells.

PMID- 24130881
TI  - The pituitary gland of the European eel reveals massive expression of genes
      involved in the melanocortin system.
AB  - Hormones secreted from the pituitary gland regulate important processes such as
      development, growth and metabolism, reproduction, water balance, and body
      pigmentation. Synthesis and secretion of pituitary hormones are regulated by
      different factors from the hypothalamus, but also through feedback mechanisms
      from peripheral organs, and from the pituitary itself. In the European eel
      extensive attention has been directed towards understanding the different
      components of the brain-pituitary-gonad axis, but little is known about the
      regulation of upstream processes in the pituitary gland. In order to gain a
      broader mechanistic understanding of the eel pituitary gland, we have performed
      RNA-seq transcriptome profiling of the pituitary of prepubertal female silver
      eels. RNA-seq reads generated on the Illumina platform were mapped to the
      recently assembled European eel genome. The most abundant transcript in the eel
      pituitary codes for pro-opiomelanocortin, the precursor for hormones of the
      melanocortin system. Several genes putatively involved in downstream processing
      of pro-opiomelanocortin were manually annotated, and were found to be highly
      expressed, both by RNA-seq and by qPCR. The melanocortin system, which affects
      skin color, energy homeostasis and in other teleosts interacts with the
      reproductive system, has so far received limited attention in eels. However,
      since up to one third of the silver eel pituitary's mRNA pool encodes pro
      opiomelanocortin, our results indicate that control of the melanocortin system is
      a major function of the eel pituitary. 

PMID- 24130882
TI  - Inhibition of caveolin-1 restores myeloid cell function in human glioblastoma.
AB  - BACKGROUND: Gliomas are the most common primary brain tumor in both children and
      adults. The prognosis for glioblastoma (GBM), the most common type of malignant
      glioma, has remained dismal, with median survival a little over one year despite
      maximal therapy with surgery, chemotherapy, and radiation. Although immunotherapy
      has become increasingly successful against many systemic tumors, clinical
      efficacy against brain tumors has been limited. One reason for this is an
      incomplete understanding of the local immunologic tumor microenvironment,
      particularly the function of large numbers of infiltrating myeloid derived cells.
      Monocytes/microglia are myeloid derived immunomodulatory cells, and they
      represent the predominant infiltrating immune cell population in gliomas. Our
      group has previously demonstrated using complementary in vitro and in vivo
      approaches that GBM tumor cells polarize tumor-associated myeloid cells (TAMs)
      and suppress their immunostimulatory function. METHODS AND RESULTS: To better
      understand the mechanisms responsible for this immunosuppression, we used gene
      expression profiling of stimulated monocytes in the presence or absence of GBM
      tumor cells. Our analysis identified caveolin-1 (CAV1), a plasma membrane
      molecule with pleiotropic functions, as significantly up-regulated in monocytes
      in the presence of GBMs. We validated these findings ex vivo by confirming up
      regulation of CAV1 in TAMs isolated from GBMs immediately after surgical
      resection. Finally, we demonstrate that siRNA inhibition of CAV1 restores myeloid
      cell function, as measured by TNF-alpha secretion, in the presence of GBMs.
      CONCLUSIONS: Restoration of TAM function through pharmacologic blockage of CAV1
      may facilitate more successful immunotherapeutic strategies directed against a
      variety of solid human tumors infiltrated by TAMs.

PMID- 24130883
TI  - Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of
      prostate cancer via Slug inhibition.
AB  - Though prostate cancer (PCa) has slow progression, the hormone refractory (HRCP)
      and metastatic entities are substantially lethal and lack effective treatments.
      Transcription factor Slug is critical in regulating metastases of various tumors
      including PCa. Here we studied targeted therapy against Slug using combination of
      3 drugs targeting 3 pathways respectively converging via Slug and further
      regulating PCa metastasis. Using in vitro assays we confirmed that Slug up
      regulation incurred inhibition of E-cadherin that was anti-metastatic, and
      inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and
      AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could
      be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines
      with different traits in terms of PTEN loss and androgen sensitivity we tested
      the efficacy of mono- and combined therapy with the drugs. We found that
      metastatic capacity of the cells was maximally inhibited only when all 3 drugs
      were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug
      expression via blockade of HSP90-dependent AR stability. Combination of rapamycin
      and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen
      insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could
      be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa
      DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors
      reduced circulating PCa cells in vivo significantly more potently than
      combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90
      inhibits metastatic capacity of prostate cancer via Slug inhibition. 

PMID- 24130884
TI  - Increasing versatility of the DNA vaccines through modification of the
      subcellular location of plasmid-encoded antigen expression in the in vivo
      transfected cells.
AB  - The route of administration of DNA vaccines can play a key role in the magnitude
      and quality of the immune response triggered after their administration. DNA
      vaccines containing the gene of the membrane-anchored glycoprotein (gpG) of the
      fish rhabdoviruses infectious haematopoietic necrosis virus (IHNV) or viral
      haematopoietic septicaemia virus (VHSV), perhaps the most effective DNA vaccines
      generated so far, confer maximum protection when injected intramuscularly in
      contrast to their low efficacy when injected intraperitoneally. In this work,
      taking as a model the DNA vaccine against VHSV, we focused on developing a more
      versatile DNA vaccine capable of inducing protective immunity regardless of the
      administration route used. For that, we designed two alternative constructs to
      gpG1-507 (the wild type membrane-anchored gpG of VHSV) encoding either a soluble
      (gpG1-462) or a secreted soluble (gpG(LmPle20-462)) form of the VHSV-gpG. In vivo
      immunisation/challenge assays showed that only gpG(LmPle20-462) (the secreted
      soluble form) conferred protective immunity against VHSV lethal challenge via
      both intramuscular and intraperitoneal injection, being this the first
      description of a fish viral DNA vaccine that confers protection when administered
      intraperitoneally. Moreover, this new DNA vaccine construct also conferred
      protection when administered in the presence of an oil adjuvant suggesting that
      DNA vaccines against rhabdoviruses could be included in the formulation of
      current multicomponent-intaperitoneally injectable fish vaccines formulated with
      an oil adjuvant. On the other hand, a strong recruitment of membrane
      immunoglobulin expressing B cells, mainly membrane IgT, as well as t-bet
      expressing T cells, at early times post-immunisation, was specifically observed
      in the fish immunised with the secreted soluble form of the VHSV-gpG protein;
      this may indicate that the subcellular location of plasmid-encoded antigen
      expression in the in vivo transfected cells could be an important factor in
      determining the ways in which DNA vaccines prime the immune response.

PMID- 24130885
TI  - Diffusion- and perfusion-weighted imaging in acute lacunar infarction: is there a
      mismatch?
AB  - PURPOSE: Characterization of lacunar infarction (LI) by use of multimodal MRI
      including diffusion- and perfusion-weighted imaging (DWI, PWI) is difficult
      because of the small lesion size. Only a few studies evaluated PWI in LI and the
      results are inconsistent. METHODS: In 16 LI patients who underwent initial MRI
      within 6 hours after symptom onset and follow-up MRI within 1 week demographics,
      clinical presentation, and MRI findings were analyzed with special emphasis on
      DWI and PWI findings. Time to peak maps were classified as showing a normal
      perfusion pattern or areas of hypoperfusion which were further categorized in
      mismatch (PWI>DWI), inverse mismatch (PWI<DWI), and match (PWI=DWI). Quantitative
      perfusion maps were generated and analyzed by use of Signal Processing in NMR
      Software (SPIN). RESULTS: Of the 16 patients (mean age 65.5+/-12.9 years), 14
      (87.5%) were male. Clinical symptoms comprised dysarthria (50%), hemiparesis
      (81.3%), and hemihypaesthesia (18.8%). Intravenous thrombolysis was performed in
      7 (43.8%) patients. Clinical improvement was observed in 12 patients (75 %),
      while 2 (12.5%) patients showed a deterioration and another 2 (12.5%) a stable
      course. Acute ischemic lesions (mean volume of 0.46+/-0.29 cm3) were located in
      the thalamus (n=8, 50%), internal capsule (n=4, 25%), corona Radiata (n=3, 18.8%)
      and the mesencephalon (n=1, 6.3%). Circumscribed hypoperfusion (mean volume
      0.61+/-0.48 cm3) was evident in 10 (62.5%) patients. Of these, 3 patients
      demonstrated a match, 4 an inverse mismatch, and 3 a mismatch between DWI and PWI
      lesion. Mean CBF and CBV ratios were 0.65+/-0.28 and 0.84+/-0.41 respectively.
      Growth of DWI lesions was observed in 7 (43.8%) and reversal of DWI lesions in 3
      (18.8%) patients. CONCLUSIONS: MRI allows identification of different DWI and PWI
      patterns in LI, including growth and reversal of ischemic lesions. Consequently,
      it may serve for a better characterization of this stroke subtype and support
      treatment decisions in daily clinical practice.

PMID- 24130886
TI  - Post-bypass dexmedetomidine use and postoperative acute kidney injury in patients
      undergoing cardiac surgery with cardiopulmonary bypass.
AB  - BACKGROUND: AND OBJECTIVES: The aim of this retrospective investigation was to
      study the relationships among chronic kidney disease, acute kidney injury (AKI),
      and potential benefits by post-bypass dexmedetomidine use in patients undergoing
      cardiac surgery. METHODS: The patient data were reviewed from the institutional
      Society of Thoracic Surgeons National Adult Cardiac Surgery Database after IRB
      approval. 1,133 patients were identified and divided into two groups: those who
      received dexmedetomidine or those who did not during the post-bypass period. The
      postoperative outcomes include the incidence of AKI, any complication and all
      cause of mortality. RESULTS: Post-bypass dexmedetomidine use was associated with
      significantly reduced the incidence of total AKI (26.1% vs. 33.75%; adjusted OR,
      0.7033; 95%CI, 0.540 to 0.916; p=0.0089). In addition, post-bypass
      dexmedetomidine use was more likely to reduce the incidence of AKI in these
      patients with preoperative normal kidney function (Stage1; 32.8% to 22.8%;
      p=0.0233) and mild CKD (Stage 2; 32.8% to 24.7; p=0.0003) after cardiac surgery.
      Post-bypass infusion of dexmedetomidine was associated with significantly reduced
      incidence of any complication and 30-day mortalities. CONCLUSIONS: Post-bypass
      dexmedetomidine use is associated with a significant reduction in the incidence
      of AKI, especially mild AKI in patients with preoperative normal renal function
      and mild CKD undergoing cardiac surgery.

PMID- 24130887
TI  - Contribution of brain size to IQ and educational underperformance in extremely
      preterm adolescents.
AB  - OBJECTIVES: Extremely preterm (EP) survivors have smaller brains, lower IQ, and
      worse educational achievement than their term-born peers. The contribution of
      smaller brain size to the IQ and educational disadvantages of EP is unknown. This
      study aimed (i) to compare brain volumes from multiple brain tissues and
      structures between EP-born (< 28 weeks) and term-born (>= 37 weeks) control
      adolescents, (ii) to explore the relationships of brain tissue volumes with IQ
      and basic educational skills and whether this differed by group, and (iii) to
      explore how much total brain tissue volume explains the underperformance of EP
      adolescents compared with controls. METHODS: Longitudinal cohort study of 148 EP
      and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic
      resonance imaging-determined brain volumes of multiple tissues and structures
      were calculated. IQ and educational skills were measured using the Wechsler
      Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT
      4), respectively. RESULTS: Brain volumes were smaller in EP adolescents compared
      with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%]
      for total brain tissue volume). The largest relative differences were noted in
      the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]),
      spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word
      reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of
      total brain tissue and other brain tissues and structures correlated positively
      with IQ and educational skills, a relationship that was similar for both the EP
      and controls. Total brain tissue volume explained between 20-40% of the IQ and
      educational outcome differences between EP and controls. CONCLUSIONS: EP
      adolescents had smaller brain volumes, lower IQs and poorer educational
      performance than controls. Brain volumes of multiple tissues and structures are
      related to IQ and educational outcomes. Smaller total brain tissue volume is an
      important contributor to the cognitive and educational underperformance of
      adolescents born EP.

PMID- 24130888
TI  - Prevalence of clonal complexes and virulence genes among commensal and invasive
      Staphylococcus aureus isolates in Sweden.
AB  - Staphylococcus aureus encodes a remarkable number of virulence factors which may
      contribute to its pathogenicity and ability to cause invasive disease. The main
      objective of this study was to evaluate the association between S. aureus
      invasiveness and bacterial genotype, in terms of the presence of virulence genes
      and affiliation to clonal complexes. Also, the significance of different
      virulence genes, mainly adhesins, for the development of infective endocarditis
      was investigated. DNA microarray technology was used to analyze 134 S. aureus
      isolates, all methicillin-susceptible, derived from three groups of clinically
      well-characterized patients: nasal carriers (n=46), bacteremia (n=55), and
      bacteremia with infective endocarditis (n=33). Invasive isolates were dominant in
      four of the major clonal complexes: 5, 8, 15, and 25. Of the 170 virulence genes
      examined, those encoding accessory gene regulator group II (agr II), capsule
      polysaccharide serotype 5 (cap5), and adhesins such as S. aureus surface protein
      G (sasG) and fibronectin-binding protein B (fnbB) were found to be associated
      with invasive disease. The same was shown for the leukocidin genes lukD/lukE, as
      well as the genes encoding serine protease A and B (splA/splB), staphylococcal
      complement inhibitor (scn) and the staphylococcal exotoxin-like protein (setC or
      selX). In addition, there was a trend of higher prevalence of certain genes or
      gene clusters (sasG, agr II, cap5) among isolates causing infective endocarditis
      compared to other invasive isolates. In most cases, the presence of virulence
      genes was linked to clonal complex affiliation. In conclusion, certain S. aureus
      clonal lineages harboring specific sets of virulence genes seem to be more
      successful in causing invasive disease.

PMID- 24130890
TI  - Pelagic life and depth: coastal physical features in West Africa shape the
      genetic structure of the Bonga Shad, Ethmalosa fimbriata.
AB  - The bonga shad, Ethmalosa fimbriata, is a West African pelagic species still
      abundant in most habitats of its distribution range and thought to be only
      recently affected by anthropogenic pressure (habitat destruction or fishing
      pressure). Its presence in a wide range of coastal habitats characterised by
      different hydrodynamic processes, represents a case study useful for evaluating
      the importance of physical structure of the west African shoreline on the genetic
      structure of a small pelagic species. To investigate this question, the genetic
      diversity of E. fimbriata was assessed at both regional and species range scales,
      using mitochondrial (mt) and nuclear DNA markers. Whereas only three panmictic
      units were identified with mtDNA at the large spatial scale, nuclear genetic
      markers (EPIC: exon-primed intron-crossing) indicated a more complex genetic
      pattern at the regional scale. In the northern-most section of shad's
      distribution range, up to 4 distinct units were identified. Bayesian inference as
      well as spatial autocorrelation methods provided evidence that gene flow is
      impeded by the presence of deep-water areas near the coastline (restricting the
      width of the coastal shelf), such as the Cap Timiris and the Kayar canyons in
      Mauritania and Senegal, respectively. The added discriminatory power provided by
      the use of EPIC markers proved to be essential to detect the influence of more
      subtle, contemporary processes (e.g. gene flow, barriers, etc.) acting within the
      glacial refuges identified previously by mtDNA. 

PMID- 24130889
TI  - Restoration of CMV-specific-CD4 T cells with ART occurs early and is greater in
      those with more advanced immunodeficiency.
AB  - OBJECTIVES: Restoration of Cytomegalovirus-specific-CD4 T cell (CMV-Sp-CD4)
      responses partly accounts for the reduction of CMV-disease with antiretroviral
      therapy (ART), but CMV-Sp-CD4 may also drive immune activation and
      immunosenescence. This study characterized the dynamics of CMV-Sp-CD4 after ART
      initiation and explored associations with CD4 T cell recovery as well as
      frequency of naive CD4 T cells at week 96. METHODS: Fifty HIV-infected, ART-naive
      Thai adults with CD4 T cell count <= 350 cells/uL and starting ART were evaluated
      over 96 weeks (ClinicalTrials.gov identifier NCT01296373). CMV-Sp-CD4 was
      detected by co-expression of CD25/CD134 by flow cytometry after CMV-antigen
      stimulation. RESULTS: All subjects were CMV sero-positive, 4 had quantifiable CMV
      DNA (range 2.3-3.9 log10 copies/mL) at baseline but none had clinically apparent
      CMV-disease. Baseline CMV-Sp-CD4 response was positive in 40 subjects. Those with
      CD4 T cell count < 100 cells/uL were less likely to have positive baseline CMV-Sp
      CD4 response (P=0.003). Positive baseline CMV-Sp-CD4 response was associated with
      reduced odds of quantifiable CMV-DNA (P=0.022). Mean CD4 T cell increase at week
      96 was 213 cells/uL. This was associated positively with baseline HIV-VL
      (P=0.001) and negatively with age (P=0.003). The frequency of CMV-Sp-CD4
      increased at week 4 (P=0.008), then declined. Those with lower baseline CMV-Sp
      CD4 (P=0.009) or CDC category C (P<0.001) had greater increases in CMV-Sp-CD4 at
      week 4. At week 96, CD4 T cell count was positively (P<0.001) and the frequency
      of CMV-Sp-CD4 was negatively (P=0.001) associated with the percentage of naive
      CD4 T cells. CONCLUSIONS: Increases in CMV-Sp-CD4 with ART occurred early and
      were greater in those with more advanced immunodeficiency. The frequency of CMV
      Sp-CD4 was associated with reduced naive CD4 T cells, a marker associated with
      immunosenescence.

PMID- 24130891
TI  - SERS properties of different sized and shaped gold nanoparticles biosynthesized
      under different environmental conditions by Neurospora crassa extract.
AB  - Surface-enhanced Raman scattering (SERS) is a surface-sensitive technique that
      enhances Raman scattering by molecules adsorbed on rough metal surfaces. It is
      known that metal nanoparticles, especially gold and silver nanoparticles, exhibit
      great SERS properties, which make them very attractive for the development of
      biosensors and biocatalysts. On the other hand, the development of ecofriendly
      methods for the synthesis of metallic nanostructures has become the focus of
      research in several countries, and many microorganisms and plants have already
      been used to biosynthesize metallic nanostructures. However, the majority of
      these are pathogenic to plants or humans. Here, we report gold nanoparticles with
      good SERS properties, biosynthesized by Neurospora crassa extract under different
      environmental conditions, increasing Raman signals up to 40 times using methylene
      blue as a target molecule. Incubation of tetrachloroauric acid solution with the
      fungal extract at 60 degrees C and a pH value of a) 3, b) 5.5, and c) 10 resulted
      in the formation of gold nanoparticles of a) different shapes like triangles,
      hexagons, pentagons etc. in a broad size range of about 10-200 nm, b) mostly
      quasi-spheres with some different shapes in a main size range of 6-23 nm, and c)
      only quasi-spheres of 3-12 nm. Analyses included TEM, HRTEM, and EDS in order to
      corroborate the shape and the elemental character of the gold nanoparticles,
      respectively. The results presented here show that these 'green' synthesized gold
      nanoparticles might have potential applicability in the field of biological
      sensing. 

PMID- 24130893
TI  - Truncated SSX protein suppresses synovial sarcoma cell proliferation by
      inhibiting the localization of SS18-SSX fusion protein.
AB  - Synovial sarcoma is a relatively rare high-grade soft tissue sarcoma that often
      develops in the limbs of young people and induces the lung and the lymph node
      metastasis resulting in poor prognosis. In patients with synovial sarcoma,
      specific chromosomal translocation of t(X; 18) (p11.2;q11.2) is observed, and
      SS18-SSX fusion protein expressed by this translocation is reported to be
      associated with pathogenesis. However, role of the fusion protein in the
      pathogenesis of synovial sarcoma has not yet been completely clarified. In this
      study, we focused on the localization patterns of SS18-SSX fusion protein. We
      constructed expression plasmids coding for the full length SS18-SSX, the
      truncated SS18 moiety (tSS18) and the truncated SSX moiety (tSSX) of SS18-SSX,
      tagged with fluorescent proteins. These plasmids were transfected in synovial
      sarcoma SYO-1 cells and we observed the expression of these proteins using a
      fluorescence microscope. The SS18-SSX fusion protein showed a characteristic
      speckle pattern in the nucleus. However, when SS18-SSX was co-expressed with
      tSSX, localization of SS18-SSX changed from speckle patterns to the diffused
      pattern similar to the localization pattern of tSSX and SSX. Furthermore, cell
      proliferation and colony formation of synovial sarcoma SYO-1 and YaFuSS cells
      were suppressed by exogenous tSSX expression. Our results suggest that the
      characteristic speckle localization pattern of SS18-SSX is strongly involved in
      the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein. These
      findings could be applied to further understand the pathogenic mechanisms, and
      towards the development of molecular targeting approach for synovial sarcoma. 

PMID- 24130892
TI  - CCR2 regulates the uptake of bone marrow-derived fibroblasts in renal fibrosis.
AB  - Recent studies have shown that bone marrow-derived fibroblasts contribute
      significantly to the pathogenesis of renal fibrosis. However, the molecular
      mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the
      kidney are incompletely understood. Bone marrow-derived fibroblasts express the
      chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2
      participates in the recruitment of fibroblasts into the kidney during the
      development of renal fibrosis. Bone marrow-derived collagen-expressing GFP+
      fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted
      with donor bone marrow from collagen alpha1(I)-GFP reporter mice. These bone
      marrow-derived fibroblasts expressed PDGFR-beta and CCR2. CCR2 knockout mice
      accumulated significantly fewer bone marrow-derived fibroblast precursors
      expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-beta
      or procollagen I in the obstructed kidneys compared with wild-type mice.
      Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived
      myofibroblasts and expressed less alpha-SMA or FSP-1 in the obstructed kidneys
      compared with wild-type mice. Consistent with these findings, genetic deletion of
      CCR2 inhibited total collagen deposition and suppressed expression of collagen I
      and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16
      gene expression associated with a reduction of inflammatory cytokine expression
      and macrophage infiltration, suggesting a linear interaction between two
      chemokines/ligand receptors in tubular epithelial cells. Taken together, our
      results demonstrate that CCR2 signaling plays an important role in the
      pathogenesis of renal fibrosis through regulation of bone marrow-derived
      fibroblasts. These data suggest that inhibition of CCR2 signaling could
      constitute a novel therapeutic approach for fibrotic kidney disease.

PMID- 24130894
TI  - Effects of cadmium on lipid storage and metabolism in the freshwater crab
      Sinopotamon henanense.
AB  - Since environmental effects of molecular traits are often questioned we analyze
      here the molecular effects of cadmium (Cd) on lipid pathways and their effects on
      tissues development. Lipids are an important energy source for the developing
      embryo, and accumulate in the ovary and hepatopancreas of decapod crustaceans.
      The extend of Cd affecting lipid storage and metabolism, is studied here with the
      freshwater crabs Sinopotamon henanense. Crabs were exposed to water-born Cd at
      1.45, 2.9, 5.8 mg/l for 10, 15, and 20 days. With significantly increased Cd
      accumulation in exposed crabs, lipid content in hepatopancreas and ovary showed a
      time-dependent and concentration-dependent reduction, being at least one of the
      reasons for a lower ovarian index (OI) and hepatopancreatic index (HI). After 10
      day exposure increased triglyceride (TG) level in hemolymph and up-regulation of
      pancreatic lipase (PL) activity in the hepatopancreas suggested an increased
      nutritional lipid uptake. However, two processes led to lower lipid levels upon
      Cd exposure: an increased utilization of lipids and a down-regulated lipoprotein
      lipase (LPL) led to insufficient lipid transport. 10-day Cd exposure also
      triggered the production of beta-nicotinamide adenine dinucleotide 2'-phosphate
      reduced tetrasodium salt hydrate (NADPH), as well as to the synthesis of
      adenosine triphosphate (ATP) and fatty acids. With increasing exposure time, the
      crabs at 15 and 20-day exposure contained less lipid and TG, suggesting that more
      energy was consumed during the exposure time. Meanwhile, the level of NADPH, ATP
      and the activity of PL, LPL, fatty acid synthase (FAS), acetyl-CoA carboxylase
      (ACC) activity was down-regulated suggesting an impairment of the crab metabolism
      by Cd in addition to causing a lower lipid level. 

PMID- 24130895
TI  - A fungal pathogen of amphibians, Batrachochytrium dendrobatidis, attenuates in
      pathogenicity with in vitro passages.
AB  - Laboratory investigations into the amphibian chytrid fungus, Batrachochytrium
      dendrobatidis (Bd), have accelerated recently, given the pathogen's role in
      causing the global decline and extinction of amphibians. Studies in which host
      animals were exposed to Bd have largely assumed that lab-maintained pathogen
      cultures retained the infective and pathogenic properties of wild isolates.
      Attenuated pathogenicity is common in artificially maintained cultures of other
      pathogenic fungi, but to date, it is unknown whether, and to what degree, Bd
      might change in culture. We compared zoospore production over time in two samples
      of a single Bd isolate having different passage histories: one maintained in
      artificial media for more than six years (JEL427-P39), and one recently thawed
      from cryopreserved stock (JEL427-P9). In a common garden experiment, we then
      exposed two different amphibian species, Eleutherodactylus coqui and Atelopus
      zeteki, to both cultures to test whether Bd attenuates in pathogenicity with in
      vitro passages. The culture with the shorter passage history, JEL427-P9, had
      significantly greater zoospore densities over time compared to JEL427-P39. This
      difference in zoospore production was associated with a difference in
      pathogenicity for a susceptible amphibian species, indicating that fecundity may
      be an important virulence factor for Bd. In the 130-day experiment, Atelopus
      zeteki frogs exposed to the JEL427-P9 culture experienced higher average
      infection intensity and 100% mortality, compared with 60% mortality for frogs
      exposed to JEL427-P39. This effect was not observed with Eleutherodactylus coqui,
      which was able to clear infection. We hypothesize that the differences in
      phenotypic performance observed with Atelopus zeteki are rooted in changes of the
      Bd genome. Future investigations enabled by this study will focus on the
      underlying mechanisms of Bd pathogenicity. 

PMID- 24130896
TI  - Rad5 template switch pathway of DNA damage tolerance determines synergism between
      cisplatin and NSC109268 in Saccharomyces cerevisiae.
AB  - The success of cisplatin (CP) based therapy is often hindered by acquisition of
      CP resistance. We isolated NSC109268 as a compound altering cellular sensitivity
      to DNA damaging agents. Previous investigation revealed an enhancement of CP
      sensitivity by NSC109268 in wild-type Saccharomyces cerevisiae and CP-sensitive
      and -resistant cancer cell lines that correlated with a slower S phase traversal.
      Here, we extended these studies to determine the target pathway(s) of NSC109268
      in mediating CP sensitization, using yeast as a model. We reasoned that mutants
      defective in the relevant target of NSC109268 should be hypersensitive to CP and
      the sensitization effect by NSC109268 should be absent or strongly reduced. A
      survey of various yeast deletion mutants converged on the Rad5 pathway of DNA
      damage tolerance by template switching as the likely target pathway of NSC109268
      in mediating cellular sensitization to CP. Additionally, cell cycle delays
      following CP treatment were not synergistically influenced by NSC109268 in the CP
      hypersensitive rad5Delta mutant. The involvement of the known inhibitory
      activities of NSC109268 on 20S proteasome and phosphatases 2Calpha and 2A was
      tested. In the CP hypersensitive ptc2Deltaptc3Deltapph3Delta yeast strain,
      deficient for 2C and 2A-type phosphatases, cellular sensitization to CP by
      NSC109268 was greatly reduced. It is therefore suggested that NSC109268 affects
      CP sensitivity by inhibiting the activity of unknown protein(s) whose
      dephosphorylation is required for the template switch pathway. 

PMID- 24130897
TI  - Rapid in vitro derivation of endothelium directly from human cancer cells.
AB  - The development of an independent blood supply by a tumor is essential for
      maintaining growth beyond a certain limited size and for providing a portal for
      metastatic dissemination. Host-derived endothelial cells (ECs) residing in and
      compromising the tumor vasculature originate via distinct processes known as
      sprouting angiogenesis and vasculogenesis. More recently ECs originating directly
      from the tumor cells themselves have been described although the basis for this
      phenomenon remains poorly understood. Here we describe in vitro conditions that
      allow lung and ovarian cancer cells to undergo a rapid and efficient transition
      into ECs that are indistinguishable from those obtained in vivo. A variety of
      methods were used to establish that the acquired phenotypes and behaviors of
      these tumor-derived ECs (TDECs) closely resemble those of authentic ECs.
      Xenografts arising from co-inoculated in vitro-derived TDECs and tumor cells were
      also more highly vascularized than control tumors; moreover, their blood vessels
      were on average larger and frequently contained admixtures of host-derived ECs
      and TDECs derived from the initial inoculum. These results demonstrate that
      cancer cells can be manipulated under well-defined in vitro conditions to
      initiate a tumor cell-to-EC transition that is largely cell-autonomous, highly
      efficient and closely mimics the in vivo process. These studies provide a
      suitable means by which to identify and perhaps modify the earliest steps in TDEC
      generation. 

PMID- 24130898
TI  - Preclinical evaluation of engineered oncolytic herpes simplex virus for the
      treatment of neuroblastoma.
AB  - Despite intensive research efforts and therapeutic advances over the last few
      decades, the pediatric neural crest tumor, neuroblastoma, continues to be
      responsible for over 15% of pediatric cancer deaths. Novel therapeutic options
      are needed for this tumor. Recently, investigators have shown that mice with
      syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic
      herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002
      has deletions in both copies of the gamma 1 34.5 gene, enabling replication in
      tumor cells but precluding infection of normal neural cells. We hypothesized that
      M002 would also be effective in the neural crest tumor, neuroblastoma. We showed
      that M002 infected, replicated, and decreased survival in neuroblastoma cell
      lines. In addition, we showed that in murine xenografts, treatment with M002
      significantly decreased tumor growth, and that this effect was augmented with the
      addition of ionizing radiation. Importantly, survival could be increased by
      subsequent doses of radiation without re-dosing of the virus. Finally, these
      studies showed that the primary entry protein for oHSV, CD111 was expressed by
      numerous neuroblastoma cell lines and was also present in human neuroblastoma
      specimens. We concluded that M002 effectively targeted neuroblastoma and that
      this oHSV may have potential for use in children with unresponsive or relapsed
      neuroblastoma. 

PMID- 24130899
TI  - HIV's Nef interacts with beta-catenin of the Wnt signaling pathway in HEK293
      cells.
AB  - The Wnt signaling pathway is implicated in major physiologic cellular functions,
      such as proliferation, migration, cell fate specification, maintenance of
      pluripotency and induction of tumorigenicity. Proliferation and migration are
      important responses of T-cells, which are major cellular targets of HIV
      infection. Using an informatics screen, we identified a previously unsuspected
      interaction between HIV's Nef protein and beta-catenin, a key component of the
      Wnt pathway. A segment in Nef contains identical amino acids at key positions and
      structurally mimics the beta-catenin binding sites on endogenous beta-catenin
      ligands. The interaction between Nef and beta-catenin was confirmed in vitro and
      in a co-immunoprecipitation from HEK293 cells. Moreover, the introduction of Nef
      into HEK293 cells specifically inhibited a Wnt pathway reporter. 

PMID- 24130900
TI  - Inhibition of sPLA2-IIA prevents LPS-induced neuroinflammation by suppressing
      ERK1/2-cPLA2alpha pathway in mice cerebral cortex.
AB  - Neuroinflammation is involved in various central nervous system (CNS) disorders,
      including brain infections, ischemia, trauma, stroke, and degenerative CNS
      diseases. In the CNS inflammation, secretory phospholipase A2-IIA (sPLA2-IIA)
      acts as a mediator, resulting in the generation of the precursors of pro
      inflammatory lipid mediators, such as prostaglandins (PGs) and leukotrienes
      (LTs). However, the role of sPLA2-IIA in neuroinflammation is more complicated
      and remains unclear yet. In the present study, we investigated the effect of
      sPLA2-IIA inhibition by specific inhibitor SC-215 on the inflammation in LPS
      induced mice cerebral cortex and primary astrocytes. Our results showed that the
      inhibition of sPLA2-IIA alleviated the release of PGE2 by suppressing the
      activation of ERK1/2, cPLA2alpha, COX-2 and mPGES-1. These findings demonstrated
      that sPLA2-IIA showed the potential to regulate the neuroinflammation in vivo and
      in vitro, indicating that sPLA2-IIA might be a novel target for the treatment of
      acute neuroinflammation.

PMID- 24130901
TI  - You are what you eat: food limitation affects reproductive fitness in a sexually
      cannibalistic praying mantid.
AB  - Resource limitation during the juvenile stages frequently results in
      developmental delays and reduced size at maturity, and dietary restriction during
      adulthood can affect longevity and reproductive output. Variation in food intake
      can also result in alteration to the normal pattern of resource allocation among
      body parts or life-history stages. My primary aim in this study was to determine
      how varying juvenile and/or adult feeding regimes affect particular female and
      male traits in the sexually cannibalistic praying mantid Pseudomantis
      albofimbriata. Praying mantids are sit-and-wait predators whose resource intake
      can vary dramatically depending on environmental conditions within and across
      seasons, making them useful for studying the effects of feeding regime on various
      facets of reproductive fitness. In this study, there was a significant
      trend/difference in development and morphology for males and females as a result
      of juvenile feeding treatment, however, its effect on the fitness components
      measured for males was much greater than on those measured for females. Food
      limited males were less likely to find a female during field enclosure
      experiments and smaller males were slower at finding a female in field-based
      experiments, providing some of the first empirical evidence of a large male size
      advantage for scrambling males. Only adult food limitation affected female
      fecundity, and the ability of a female to chemically attract males was also most
      notably affected by adult feeding regime (although juvenile food limitation did
      play a role). Furthermore, the significant difference/trend in all male traits
      and the lack of difference in male trait ratios between treatments suggests a
      proportional distribution of resources and, therefore, no trait conservation by
      food-limited males. This study provides evidence that males and females are under
      different selective pressures with respect to resource acquisition and is also
      one of very few to show an effect of juvenile food quantity on adult reproductive
      fitness in a hemimetabolous insect. 

PMID- 24130902
TI  - Visfatin as a novel mediator released by inflamed human endothelial cells.
AB  - BACKGROUND: Visfatin is a multifaceted adipokine whose circulating levels are
      enhanced in different metabolic diseases. Extracellular visfatin can exert
      various deleterious effects on vascular cells, including inflammation and
      proliferation. Limited evidence exists, however, on the capacity of human
      vascular cells to synthesize and release visfatin by themselves, under basal or
      pro-inflammatory conditions. METHODS AND RESULTS: Intracellular visfatin was
      detected by Western blot in non-stimulated human umbilical vein endothelial cells
      (HUVEC). However, exposing HUVEC for 18 h to a series of pro-inflammatory
      stimulus, such as interleukin (IL)-1beta (1 to 10 ng/mL), tumor necrosis factor
      alpha (1 to 10 ng/mL) or angiotensin II (10 pmol/L to 1 MUmol/L) markedly
      enhanced intracellular visfatin content. Using IL-1beta (10 ng/mL; 18 h), it was
      determined that the increase in intracellular visfatin, which was paralleled by
      enhanced visfatin mRNA levels, relied on a signalling mechanism involving both
      nuclear factor-kappaB and poly (ADP ribose) polymerase-1 activation. Moreover, IL
      1beta modified the sub-cellular localization of visfatin; while in non-stimulated
      HUVEC immunoreactive visfatin predominantly showed an intra-nuclear granular
      pattern, in IL-1beta-inflamed cells an extra-nuclear filamentous staining, co
      localising with F-actin fibers and suggesting a secretory pattern, was mainly
      found. Indeed, IL-1beta promoted visfatin secretion, as determined by both ELISA
      and immunocytochemistry. CONCLUSIONS: Human endothelial cells synthesize and
      release visfatin, particularly in response to inflammation. We suggest that the
      inflamed endothelium can be a source of visfatin, which arises as a local
      inflammatory mediator and a potential therapeutic target to interfere with
      vascular inflammation.

PMID- 24130903
TI  - Detecting depression in patients with coronary heart disease: a diagnostic
      evaluation of the PHQ-9 and HADS-D in primary care, findings from the UPBEAT-UK
      study.
AB  - OBJECTIVE: People with coronary heart disease (CHD) are at heightened risk of
      depression, and this co-occurrence of conditions is associated with poorer
      outcomes including raised mortality. This study compares the diagnostic accuracy
      of two depression case finding instruments in CHD patients relative to a
      diagnostic standard, the revised Clinical Interview Schedule (CIS-R). METHODS:
      The Patient Health Questionnaire (PHQ-9), the Hospital Anxiety and Depression
      Scale depression subscale (HADS-D) and the CIS-R depression module were
      administered to 803 patients identified from the CHD registers of GP practices in
      Greater London. RESULTS: Of 730 recruited patients without previously identified
      depression, 32 (4.4%) met ICD-10 depressive episode criteria according to the CIS
      R. For the PHQ-9 and HADS-D lower cut-points than those routinely recommended
      were associated with improved case identifying properties. The PHQ-9 appeared the
      superior instrument using a cut-point of >=8 (sensitivity=94%; specificity=84%).
      Using categorical scoring the PHQ-9 was 59% sensitive and 95% specific. For the
      HADS-D using cut-point >=5, sensitivity was 81% and specificity was 77%. Areas
      under the curves (AUC) (standard error) were 0.95 (0.01) and 0.88 (0.02) for the
      PHQ-9 and HADS-D, and 0.91 (0.02) for PHQ-9 using the categorical algorithm.
      Statistically significant differences between AUCs of the PHQ-9 and the HADS-D
      favoured the former. Severity ratings compared across measures indicated
      inconsistency between recommended bandings: the PHQ-9 categorised a larger
      proportion of participants with mild and moderate depression. CONCLUSION: This is
      the first large-scale investigation of the accuracy of these commonly used
      measures within a primary care CHD population. Our results suggest that although
      both scales have acceptable abilities and can be used as case identification
      instruments for depression in patients with CHD, the PHQ-9 appeared
      diagnostically superior. Importantly, optimal cut-off points for depression
      identification in this population appear to differ from standard values, and
      severity ratings differ between these measures.

PMID- 24130904
TI  - Muscular and systemic correlates of resistance training-induced muscle
      hypertrophy.
AB  - PURPOSE: To determine relationships between post-exercise changes in systemic
      [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and
      interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR)
      protein content and p70S6K phosphorylation status] factors in a moderately-sized
      cohort of young men exhibiting divergent resistance training-mediated muscle
      hypertrophy. METHODS: Twenty three adult males completed 4 sessions*wk-1 of
      resistance training for 16 wk. Muscle biopsies were obtained before and after the
      training period and acutely 1 and 5 h after the first training session. Serum
      hormones and cytokines were measured immediately, 15, 30 and 60 minutes following
      the first and last training sessions of the study. RESULTS: Mean fiber area
      increased by 20% (range: -7 to 80%; P<0.001). Protein content of the AR was
      unchanged with training (fold change = 1.17 +/- 0.61; P=0.19); however, there was
      a significant correlation between the changes in AR content and fiber area
      (r=0.60, P=0.023). Phosphorylation of p70S6K was elevated 5 hours following
      exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007).
      There was no relationship between the magnitude of the pre- or post-training
      exercise-induced changes in free testosterone, GH, or IGF-1 concentration and
      muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6
      response was correlated with muscle hypertrophy (r=0.48, P=0.019). CONCLUSION:
      Post-exercise increases in circulating hormones are not related to hypertrophy
      following training. Exercise-induced changes in IL-6 correlated with hypertrophy,
      but the mechanism for the role of IL-6 in hypertrophy is not known. Acute
      increases, in p70S6K phosphorylation and changes in muscle AR protein content
      correlated with muscle hypertrophy implicating intramuscular rather than systemic
      processes in mediating hypertrophy.

PMID- 24130905
TI  - Comparisons of microRNA patterns in plasma before and after tumor removal reveal
      new biomarkers of lung squamous cell carcinoma.
AB  - Lung cancer is the major human malignancy, accounting for 30% of all cancer
      related deaths worldwide. Poor survival of lung cancer patients, together with
      late diagnosis and resistance to classic chemotherapy, highlights the need for
      identification of new biomarkers for early detection. Among different cancer
      biomarkers, small non-coding RNAs called microRNAs (miRNAs) are considered the
      most promising, owing to their remarkable stability, their cancer-type
      specificity, and their presence in body fluids. However, results of multiple
      previous attempts to identify circulating miRNAs specific for lung cancer are
      inconsistent, likely due to two main reasons: prominent variability in blood
      miRNA content among individuals and difficulties in distinguishing tumor-relevant
      miRNAs in the blood from their non-tumor counterparts. To overcome these
      impediments, we compared circulating miRNA profiles in patients with lung
      squamous cell carcinoma (SCC) before and after tumor removal, assuming that the
      levels of all tumor-relevant miRNAs would drop after the surgery. Our results
      revealed a specific panel of the miRNAs (miR-205, -19a, -19b, -30b, and -20a)
      whose levels decreased strikingly in the blood of patients after lung SCC
      surgery. Interestingly, miRNA profiling of plasma fractions of lung SCC patients
      revealed high levels of these miRNA species in tumor-specific exosomes;
      additionally, some of these miRNAs were also found to be selectively secreted to
      the medium by cultivated lung cancer cells. These results strengthen the notion
      that tumor cells secrete miRNA-containing exosomes into circulation, and that
      miRNA profiling of the exosomal plasma fraction may reveal powerful cancer
      biomarkers. 

PMID- 24130906
TI  - Differential roles for EphA and EphB signaling in segregation and patterning of
      central vestibulocochlear nerve projections.
AB  - Auditory and vestibular afferents enter the brainstem through the VIIIth cranial
      nerve and find targets in distinct brain regions. We previously reported that the
      axon guidance molecules EphA4 and EphB2 have largely complementary expression
      patterns in the developing avian VIIIth nerve. Here, we tested whether inhibition
      of Eph signaling alters central targeting of VIIIth nerve axons. We first
      identified the central compartments through which auditory and vestibular axons
      travel. We then manipulated Eph-ephrin signaling using pharmacological inhibition
      of Eph receptors and in ovo electroporation to misexpress EphA4 and EphB2.
      Anterograde labeling of auditory afferents showed that inhibition of Eph
      signaling did not misroute axons to non-auditory target regions. Similarly, we
      did not find vestibular axons within auditory projection regions. However, we
      found that pharmacologic inhibition of Eph receptors reduced the volume of the
      vestibular projection compartment. Inhibition of EphB signaling alone did not
      affect auditory or vestibular central projection volumes, but it significantly
      increased the area of the auditory sensory epithelium. Misexpression of EphA4 and
      EphB2 in VIIIth nerve axons resulted in a significant shift of dorsoventral
      spacing between the axon tracts, suggesting a cell-autonomous role for the
      partitioning of projection areas along this axis. Cochlear ganglion volumes did
      not differ among treatment groups, indicating the changes seen were not due to a
      gain or loss of cochlear ganglion cells. These results suggest that Eph-ephrin
      signaling does not specify auditory versus vestibular targets but rather
      contributes to formation of boundaries for patterning of inner ear projections in
      the hindbrain. 

PMID- 24130907
TI  - TLR and NKG2D signaling pathways mediate CS-induced pulmonary pathologies.
AB  - Long-term exposure to cigarette smoke (CS) can have deleterious effects on lung
      epithelial cells including cell death and the initiation of inflammatory
      responses. CS-induced cell injury can elaborate cell surface signals and cellular
      byproducts that stimulate immune system surveillance. Our previous work has shown
      that the expression of ligands for the cytotoxic lymphocyte activating receptor
      NKG2D is enhanced in patients with COPD and that the induction of these ligands
      in a mouse model can replicate COPD pathologies. Here, we extend these findings
      to demonstrate a role for the NKG2D receptor in CS-induced pathophysiology and
      provide evidence linking nucleic acid-sensing endosomal toll-like receptor (TLR)
      signaling to COPD pathology through NKG2D activation. Specifically, we show that
      mice deficient in NKG2D exhibit attenuated pulmonary inflammation and airspace
      enlargement in a model of CS-induced emphysema. Additionally, we show that CS
      exposure induces the release of free nucleic acids in the bronchoalveolar lavage
      and that direct exposure of mouse lung epithelial cells to cigarette smoke
      extract similarly induces functional nucleic acids as assessed by TLR3, 7, and 9
      reporter cell lines. We demonstrate that exposure of mouse lung epithelial cells
      to TLR ligands stimulates the surface expression of RAET1, a ligand for NKG2D,
      and that mice deficient in TLR3/7/9 receptor signaling do not exhibit CS-induced
      NK cell hyperresponsiveness and airspace enlargement. The findings indicate that
      CS-induced airway injury stimulates TLR signaling by endogenous nucleic acids
      leading to elevated NKG2D ligand expression. Activation of these pathways plays a
      major role in the altered NK cell function, pulmonary inflammation and remodeling
      related to long-term CS exposure. 

PMID- 24130908
TI  - Ten years of podoconiosis research in Ethiopia.

PMID- 24130910
TI  - Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate
      with decreased susceptibility to pentamidine and melarsoprol.
AB  - The predominant mechanism of drug resistance in African trypanosomes is decreased
      drug uptake due to loss-of-function mutations in the genes for the transporters
      that mediate drug import. The role of transporters as determinants of drug
      susceptibility is well documented from laboratory-selected Trypanosoma brucei
      mutants. But clinical isolates, especially of T. b. gambiense, are less amenable
      to experimental investigation since they do not readily grow in culture without
      prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field
      isolates that (i) have been adapted to axenic in vitro cultivation and (ii)
      mostly stem from treatment-refractory cases. For each isolate, we quantify the
      sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic
      loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well
      characterized aminopurine permease P2 which transports several trypanocides
      including melarsoprol, pentamidine, and diminazene. We find that diminazene
      resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set
      of point mutations in TbAT1 that was previously described from lab mutants.
      Aquaglyceroporin 2 has only recently been identified as a second transporter
      involved in melarsoprol/pentamidine cross-resistance. Here we describe two
      different kinds of TbAQP2 mutations found in T. b. gambiense field isolates:
      simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the
      formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b.
      gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less
      sensitive to melarsoprol than the reference isolates. We thus demonstrate for the
      first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2
      gene loss also occur in the field, and that the T. b. gambiense carrying such
      mutations correlate with a significantly reduced susceptibility to pentamidine
      and melarsoprol. 

PMID- 24130909
TI  - Neurotoxicity in snakebite--the limits of our knowledge.
AB  - Snakebite is classified by the WHO as a neglected tropical disease. Envenoming is
      a significant public health problem in tropical and subtropical regions.
      Neurotoxicity is a key feature of some envenomings, and there are many unanswered
      questions regarding this manifestation. Acute neuromuscular weakness with
      respiratory involvement is the most clinically important neurotoxic effect. Data
      is limited on the many other acute neurotoxic manifestations, and especially
      delayed neurotoxicity. Symptom evolution and recovery, patterns of weakness,
      respiratory involvement, and response to antivenom and acetyl cholinesterase
      inhibitors are variable, and seem to depend on the snake species, type of
      neurotoxicity, and geographical variations. Recent data have challenged the
      traditional concepts of neurotoxicity in snake envenoming, and highlight the rich
      diversity of snake neurotoxins. A uniform system of classification of the pattern
      of neuromuscular weakness and models for predicting type of toxicity and
      development of respiratory weakness are still lacking, and would greatly aid
      clinical decision making and future research. This review attempts to update the
      reader on the current state of knowledge regarding this important issue. 

PMID- 24130911
TI  - Responses of murine and human macrophages to leptospiral infection: a study using
      comparative array analysis.
AB  - Leptospirosis is a re-emerging tropical infectious disease caused by pathogenic
      Leptospira spp. The different host innate immune responses are partially related
      to the different severities of leptospirosis. In this study, we employed
      transcriptomics and cytokine arrays to comparatively calculate the responses of
      murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HBMs)
      to leptospiral infection. We uncovered a series of different expression profiles
      of these two immune cells. The percentages of regulated genes in several
      biological processes of MPMs, such as antigen processing and presentation,
      membrane potential regulation, and the innate immune response, etc., were much
      greater than those of HBMs (>2-fold). In MPMs and HBMs, the caspase-8 and Fas
      associated protein with death domain (FADD)-like apoptosis regulator genes were
      significantly up-regulated, which supported previous results that the caspase-8
      and caspase-3 pathways play an important role in macrophage apoptosis during
      leptospiral infection. In addition, the key component of the complement pathway,
      C3, was only up-regulated in MPMs. Furthermore, several cytokines, e.g.
      interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), were
      differentially expressed at both mRNA and protein levels in MPMs and HBMs. Some
      of the differential expressions were proved to be pathogenic Leptospira-specific
      regulations at mRNA level or protein level. Though it is still unclear why some
      animals are resistant and others are susceptible to leptospiral infection, this
      comparative study based on transcriptomics and cytokine arrays partially
      uncovered the differences of murine resistance and human susceptibility to
      leptospirosis. Taken together, these findings will facilitate further molecular
      studies on the innate immune response to leptospiral infection. 

PMID- 24130912
TI  - CSF CXCL10, CXCL9, and neopterin as candidate prognostic biomarkers for HTLV-1
      associated myelopathy/tropical spastic paraparesis.
AB  - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) -associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic
      neuroinflammatory disease. Since the disease course of HAM/TSP varies among
      patients, there is a dire need for biomarkers capable of predicting the rate of
      disease progression. However, there have been no studies to date that have
      compared the prognostic values of multiple potential biomarkers for HAM/TSP.
      METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood and cerebrospinal fluid (CSF)
      samples from HAM/TSP patients and HTLV-1-infected control subjects were obtained
      and tested retrospectively for several potential biomarkers, including chemokines
      and other cytokines, and nine optimal candidates were selected based on receiver
      operating characteristic (ROC) analysis. Next, we evaluated the relationship
      between these candidates and the rate of disease progression in HAM/TSP patients,
      beginning with a first cohort of 30 patients (Training Set) and proceeding to a
      second cohort of 23 patients (Test Set). We defined "deteriorating HAM/TSP" as
      distinctly worsening function (>=3 grades on Osame's Motor Disability Score
      (OMDS)) over four years and "stable HAM/TSP" as unchanged or only slightly
      worsened function (1 grade on OMDS) over four years, and we compared the levels
      of the candidate biomarkers in patients divided into these two groups. The CSF
      levels of chemokine (C-X-C motif) ligand 10 (CXCL10), CXCL9, and neopterin were
      well-correlated with disease progression, better even than HTLV-1 proviral load
      in PBMCs. Importantly, these results were validated using the Test Set.
      CONCLUSIONS/SIGNIFICANCE: As the CSF levels of CXCL10, CXCL9, and neopterin were
      the most strongly correlated with rate of disease progression, they represent the
      most viable candidates for HAM/TSP prognostic biomarkers. The identification of
      effective prognostic biomarkers could lead to earlier detection of high-risk
      patients, more patient-specific treatment options, and more productive clinical
      trials.

PMID- 24130913
TI  - The dispersal ecology of Rhodesian sleeping sickness following its introduction
      to a new area.
AB  - Tsetse-transmitted human and animal trypanosomiasis are constraints to both human
      and animal health in sub-Saharan Africa, and although these diseases have been
      known for over a century, there is little recent evidence demonstrating how the
      parasites circulate in natural hosts and ecosystems. The spread of Rhodesian
      sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over
      the past 15 years has been linked to the movement of infected, untreated
      livestock (the predominant reservoir) from endemic areas. However, despite an
      understanding of the environmental dependencies of sleeping sickness, little
      research has focused on the environmental factors controlling transmission
      establishment or the spatially heterogeneous dispersal of disease following a new
      introduction. In the current study, an annually stratified case-control study of
      Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow
      the temporal assessment of correlations between the spatial distribution of
      sleeping sickness and landscape factors. Significant relationships were detected
      between Rhodesian sleeping sickness and selected factors, including elevation and
      the proportion of land which was "seasonally flooding grassland" or "woodlands
      and dense savannah." Temporal trends in these relationships were detected,
      illustrating the dispersal of Rhodesian sleeping sickness into more 'suitable'
      areas over time, with diminishing dependence on the point of introduction in
      concurrence with an increasing dependence on environmental and landscape factors.
      These results provide a novel insight into the ecology of Rhodesian sleeping
      sickness dispersal and may contribute towards the implementation of evidence
      based control measures to prevent its further spread. 

PMID- 24130914
TI  - Functional and genetic characterization of neuropeptide Y-like receptors in Aedes
      aegypti.
AB  - BACKGROUND: Female Aedes aegypti mosquitoes are the principal vector for dengue
      fever, causing 50-100 million infections per year, transmitted between human and
      mosquito by blood feeding. Ae. aegypti host-seeking behavior is known to be
      inhibited for three days following a blood meal by a hemolymph-borne humoral
      factor. Head Peptide-I is a candidate peptide mediating this suppression, but the
      mechanism by which this peptide alters mosquito behavior and the receptor through
      which it signals are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Head Peptide-I
      shows sequence similarity to short Neuropeptide-F peptides (sNPFs) that have been
      implicated in feeding behaviors and are known to signal through Neuropeptide Y
      (NPY)-Like Receptors (NPYLRs). We identified eight NPYLRs in the Ae. aegypti
      genome and screened each in a cell-based calcium imaging assay for sensitivity
      against a panel of peptides. Four of the Ae. aegypti NPYLRs responded to one or
      more peptide ligands, but only NYPLR1 responded to Head Peptide-I as well as
      sNPFs. Two NPYLR1 homologues identified in the genome of the Lyme disease vector,
      Ixodes scapularis, were also sensitive to Head Peptide-I. Injection of synthetic
      Head Peptide-I and sNPF-3 inhibited host-seeking behavior in non-blood-fed female
      mosquitoes, whereas control injections of buffer or inactive Head Peptide-I
      [Cys10] had no effect. To ask if NPYLR1 is necessary for blood-feeding-induced
      host-seeking inhibition, we used zinc-finger nucleases to generate five
      independent npylr1 null mutant strains and tested them for behavioral
      abnormalities. npylr1 mutants displayed normal behavior in locomotion, egg
      laying, sugar feeding, blood feeding, host seeking, and inhibition of host
      seeking after a blood meal. CONCLUSIONS: In this work we deorphanized four Ae.
      aegypti NPYLRs and identified NPYLR1 as a candidate sNPF receptor that is also
      sensitive to Head Peptide-I. Yet npylr1 alone is not required for host-seeking
      inhibition and we conclude that other receptors, additional peptides, or both,
      regulate this important behavior.

PMID- 24130915
TI  - Invasive non-typhoidal Salmonella typhimurium ST313 are not host-restricted and
      have an invasive phenotype in experimentally infected chickens.
AB  - Salmonella enterica serovar Typhimurium Sequence Type (ST) 313 is a major cause
      of invasive non-Typhoidal salmonellosis in sub-Saharan Africa. No animal
      reservoir has been identified, and it has been suggested that ST313 is adapted to
      humans and transmission may occur via person-to-person spread. Here, we show that
      ST313 cause severe invasive infection in chickens as well as humans. Oral
      infection of chickens with ST313 isolates D23580 and Q456 resulted in rapid
      infection of spleen and liver with all birds infected at these sites by 3 days
      post-infection. In contrast, the well-defined ST19 S. Typhimurium isolates F98
      and 4/74 were slower to cause invasive disease. Both ST19 and ST313 caused
      hepatosplenomegaly, and this was most pronounced in the ST313-infected animals.
      At 3 and 7 days post-infection, colonization of the gastrointestinal tract was
      lower in birds infected with the ST313 isolates compared with ST19. Histological
      examination and expression of CXCL chemokines in the ileum showed that both
      D23580 (ST313) and 4/74 (ST19) strains caused increased CXCL expression at 3 days
      post-infection, and this was significantly higher in the ileum of D23580 vs 4/74
      infected birds. At 7 days post-infection, reduced chemokine expression occurred
      in the ileum of the D23580 but not 4/74-infected birds. Histological analysis
      showed that D23580 infection resulted in rapid inflammation and pathology
      including villous flattening and fusion at 3 days post-infection, and subsequent
      resolution by 7 days. In contrast, 4/74 induced less inflammation and pathology
      at 3 days post-infection. The data presented demonstrate that ST313 is capable of
      causing invasive disease in a non-human host. The rapid invasive nature of
      infection in the chicken, coupled with lower gastrointestinal colonization,
      supports the hypothesis that ST313 is a distinct pathovariant of S. Typhimurium
      that has evolved to become a systemic pathogen that can cause disease in several
      hosts. 

PMID- 24130916
TI  - Natural terpenoids from Ambrosia species are active in vitro and in vivo against
      human pathogenic trypanosomatids.
AB  - Among the natural compounds, terpenoids play an important role in the drug
      discovery process for tropical diseases. The aim of the present work was to
      isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The
      sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two
      other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol,
      were isolated from A. scabra. Cumanin and cordilin were active against
      Trypanosoma cruzi epimastigotes showing 50% inhibition concentrations (IC50)
      values of 12 uM and 26 uM, respectively. Moreover, these compounds are active
      against bloodstream trypomastigotes, regardless of the T. cruzi strain tested.
      Psilostachyin and cumanin were also active against amastigote forms with IC50
      values of 21 uM and 8 uM, respectively. By contrast, daucosterol showed moderate
      activity on epimastigotes and trypomastigotes and was inactive against amastigote
      forms. We also found that cumanin and psilostachyin exhibited an additive effect
      in their trypanocidal activity when these two drugs were tested together. Cumanin
      has leishmanicidal activity with growth inhibition values greater than 80% at a
      concentration of 5 ug/ml (19 uM), against both L. braziliensis and L. amazonensis
      promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active
      than benznidazole, producing an 8-fold reduction in parasitemia levels during the
      acute phase of the infection compared with the control group, and more
      importantly, a reduction in mortality with 66% of the animals surviving, in
      comparison with 100% mortality in the control group. Cumanin also showed nontoxic
      effects at the doses assayed in vivo, as determined using markers of hepatic
      damage.

PMID- 24130918
TI  - Double superior vena cava on fistulogram: A case report and discussion.
AB  - PATIENT: Female, 50 FINAL DIAGNOSIS: Double superior vena cava Symptoms: -
      MEDICATION: - Clinical Procedure: - Specialty: Nephrology. OBJECTIVE: Anatomical
      anomaly/variation. BACKGROUND: Superior vena cava anomalies are caused by
      variations in the development of the embryonic thoracic venous system.
      Duplication of the superior vena cava is a rare anomaly with an incidence in the
      general population of 0.3%. The majority of cases are asymptomatic and diagnosed
      incidentally by imaging done for another reason. CASE REPORT: A fifty year old
      female patient presented to our care with a history of end stage renal disease
      that has been recently started on dialysis. Procedures performed included a
      fistulogram, PermaCath placement and angiogram of internal jugular vein.
      Angiogram was done and showed that the patient has a good sized cephalic vein
      which is wide open and mild to moderate stenosis at the subclavian area which
      proved to be a dual superior vena cava. CONCLUSIONS: Double SVC is a rare
      congenital anomaly. The literature available on this congenital anomaly is
      sparse. The majority of cases are diagnosed incidentally on imaging for other
      reasons, which can alert the physician of other congenital abnormalities that
      will need further work up. However, these venous anomalies should be recognized,
      as they can have significant clinical implications, especially during central
      venous catheter placement, radiofrequency ablation, pacemaker insertion or
      coronary artery bypass graft.

PMID- 24130917
TI  - Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.
AB  - Anti-dengue T-cell responses have been implicated in both protection and
      immunopathology. However, most of the T-cell studies for dengue include few
      epitopes, with limited knowledge of their inter-serotype variation and the
      breadth of their human leukocyte antigen (HLA) affinity. In order to expand our
      knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against
      477 overlapping peptides derived from structural and non-structural proteins of
      the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice
      (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and
      the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and
      97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in
      TgM and their HLA affinity was further confirmed by binding assays analysis. A
      subset of these epitopes activated memory T-cells from DENV3 immune volunteers
      and was also capable of priming naive T-cells, ex vivo, from dengue IgG negative
      individuals. Analysis of inter- and intra-serotype variation of such an epitope
      (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3
      but also in other DENV serotypes. These studies also characterized the HLA
      promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six
      of which could bind to more than 10 different HLA molecules representing a large
      percentage of the global population. These epitope data are invaluable to
      investigate the role of T-cells in dengue immunity/pathogenesis and vaccine
      design. 

PMID- 24130919
TI  - Sinus of valsalva aneurysm with fistula to the right atrium presented as acute
      heart failure in a young man.
AB  - PATIENT: Male, 23 FINAL DIAGNOSIS: Sinus of valsalva aneurysm (SVA) Symptoms:
      Chest pain * low O2 saturation * short of breath MEDICATION: - Clinical
      Procedure: - Specialty: Cardiology. OBJECTIVE: Rare disease. BACKGROUND: Sinus of
      valsalva aneurysm (SVA) is a rare cardiac anomaly. It may be congenital or
      acquired; a coexisting cardiac lesion might be present. Rupture of the aneurysm,
      where it usually occurs in the right atrium, can cause acute symptoms of heart
      failure. Echocardiography (particularly TEE) can provide all necessary diagnostic
      data for safe surgical treatment. Treatment of choice is surgery. CASE REPORT: A
      23-year-old male, previously healthy, presented to the emergency room (ER) with
      shortness of breath for the last 10 hours after lifting a heavy object. The
      patient had central chest pain. His O2 sat was 88%. ECG showed ischemic changes.
      Diagnosis of AMI was made, but auscultation revealed a murmur followed by a TTE
      and TEE, which revealed a ruptured sinus of valsalva aneurysm. CONCLUSIONS: This
      case report highlights the superiority of TEE over TTE in diagnosis and in
      planning adequate surgical treatment for patients with ruptured SVA, as well as
      the importance of ultrasonographer experience in the diagnosis. The optimal
      management for a ruptured SVA is surgical repair, with an acceptably low
      operative risk and good long-term outcome.

PMID- 24130920
TI  - Mechanisms of Amyloid-beta Peptide Clearance: Potential Therapeutic Targets for
      Alzheimer's Disease.
AB  - Amyloid-beta peptide (Abeta) is still best known as a molecule to cause
      Alzheimer's disease (AD) through accumulation and deposition within the frontal
      cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have
      been focused on the reduc-tion of Abeta in the brain. Since accumulation of Abeta
      depends on the rate of its synthesis and clearance, the metabolic pathway of
      Abeta in the brain and the whole body should be carefully explored for AD
      research. Although the synthetic pathway of Abeta is equally important, we
      summarize primarily the clearance pathway in this paper because the former has
      been extensively reviewed in previous studies. The clearance of Abeta from the
      brain is accomplished by several mechanisms which include non-enzymatic and
      enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage,
      uptake by microglial phagocytosis, and transport across the blood vessel walls
      into the circulation. Multiple Abeta-degrading enzymes (ADE) implicated in the
      clearance process have been identified, which include neprilysin, insulin
      degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and
      others. A series of studies on Abeta clearance mechanism provide new insight into
      the pathogenesis of AD at the molecular level and suggest a new target for the
      development of novel therapeutics. 

PMID- 24130922
TI  - Drug-induced nephrotoxicity and its biomarkers.
AB  - Nephrotoxicity occurs when kidney-specific detoxification and excretion do not
      work properly due to the damage or destruction of kidney function by exogenous or
      endogenous toxicants. Exposure to drugs often results in toxicity in kidney which
      represents the major control system maintaining homeostasis of body and thus is
      especially susceptible to xenobiotics. Understanding the toxic mechanisms for
      nephrotoxicity provides useful information on the development of drugs with
      therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced
      nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity,
      inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic
      microangiopathy. Biomarkers have been identifi ed for the assessment of
      nephrotoxicity. The discovery and development of novel biomarkers that can
      diagnose kidney damage earlier and more accurately are needed for effective
      prevention of drug-induced nephrotoxicity. Although some of them fail to confer
      specificity and sensitivity, several promising candidates of biomarkers were
      recently proved for assessment of nephrotoxicity. In this review, we summarize
      mechanisms of drug-induced nephrotoxicity and present the list of drugs that
      cause nephrotoxicity and biomarkers that can be used for early assessment of
      nephrotoxicity. 

PMID- 24130921
TI  - Tamoxifen resistance in breast cancer.
AB  - Tamoxifen is a central component of the treatment of estrogen receptor (ER)
      positive breast cancer as a partial agonist of ER. It has been clinically used
      for the last 30 years and is currently available as a chemopreventive agent in
      women with high risk for breast cancer. The most challenging issue with tamoxifen
      use is the development of resistance in an initially responsive breast tumor.
      This review summarizes the roles of ER as the therapeutic target of tamoxifen in
      cancer treatment, clinical values and issues of tamoxifen use, and molecular
      mechanisms of tamoxifen resistance. Emerging knowledge on the molecular
      mechanisms of tamoxifen resistance will provide insight into the design of
      regimens to overcome tamoxifen resistance and discovery of novel therapeutic
      agents with a decreased chance of developing resistance as well as establishing
      more efficient treatment strategies. 

PMID- 24130923
TI  - Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO
      211H Cells.
AB  - Hesperidin, a flavanone present in citrus fruits, has been studied as potential
      therapeutic agents that have anti-tumor activity and apoptotic effects in several
      cancers, but there is no report about the apoptotic effect of hesperidin in human
      malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein.
      We investigated whether hesperidin inhibited cell growth and regulated Sp1 target
      proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The IC50
      value of hesperidin was determined to be 152.3 MUM in MSTO-211H cells for 48 h.
      Our results suggested that hesperidin (0-160 MUM) decreased cell viability, and
      induced apoptotic cell death. Hesperidin increased Sub-G1 population in MSTO-211H
      cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and
      modulated the expression level of the Sp1 regulatory protein such as p27, p21,
      cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced
      apoptotic signaling including: cleavages of Bid, caspase-3, and PARP,
      upregulation of Bax, and down-regulation of Bcl-xl in mesothelioma cells. These
      results show that hesperidin suppressed mesothelioma cell growth through
      inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel
      molecular target of hesperidin in human malignant pleural mesothelioma. 

PMID- 24130924
TI  - Suppression of HIF-1alpha by Valproic Acid Sustains Self-Renewal of Mouse
      Embryonic Stem Cells under Hypoxia In Vitro.
AB  - The developing embryo naturally experiences relatively low oxygen conditions in
      vivo. Under in vitro hypoxia, mouse embryonic stem cells (mESCs) lose their self
      renewal activity and display an early differentiated morphology mediated by the
      hypoxia-inducible factor-1alpha (HIF-1alpha). Previously, we demonstrated that
      histone deacetylase (HDAC) is activated by hypoxia and increases the protein
      stability and transcriptional activity of HIF-1alpha in many human cancer cells.
      Furthermore HDAC1 and 3 mediate the differentiation of mECSs and hematopoietic
      stem cells. However, the role of HDACs and their inhibitors in hypoxia-induced
      early differentiation of mESCs remains largely unknown. Here, we examined the
      effects of several histone deacetylase inhibitors (HDA-CIs) on the self-renewal
      properties of mESCs under hypoxia. Inhibition of HDAC under hypoxia effectively
      decreased the HIF-1alpha protein levels and substantially improved the expression
      of the LIF-specific receptor (LIFR) and phosphorylated-STAT3 in mESCs. In
      particular, valproic acid (VPA), a pan HDACI, showed dramatic changes in HIF
      1alpha protein levels and LIFR protein expression levels compared to other
      HDACIs, including sodium butyrate (SB), trichostatin A (TSA), and apicidin (AP).
      Importantly, our RT-PCR data and alkaline phosphatase assays indicate that VPA
      helps to maintain the self-renewal activity of mESCs under hypoxia. Taken
      together, these results suggest that VPA may block the early differentiation of
      mESCs under hypoxia via the destabilization of HIF-1alpha. 

PMID- 24130925
TI  - Transglutaminase-2 Is Involved in All-Trans Retinoic Acid-Induced Invasion and
      Matrix Metalloproteinases Expression of SH-SY5Y Neuroblastoma Cells via NF-kappaB
      Pathway.
AB  - All-trans retinoic acid (ATRA) is currently used in adjuvant differentiation
      based treatment of residual or relapsed neuroblastoma (NB). It has been reported
      that short-term ATRA treatment induces migration and invasion of SH-SY5Y via
      transglutaminase-2 (Tgase-2). However, the detailed mechanism of Tgase-2's
      involvement in NB cell invasion remains unclear. Therefore we investigated the
      role of Tgase-2 in invasion of NB cells using SH-SY5Y cells. ATRA dose
      dependently induced the invasion of SH-SY5Y cells. Cystamine (CTM), a well known
      tgase inhibitor suppressed the ATRA-induced invasion of SH-SY5Y cells in a dose
      dependent manner. Matrix metalloproteinase-9 (MMP-9) and MMP-2, well known genes
      involved in invasion of cancer cells were induced in the ATRA-induced invasion of
      the SH-SH5Y cells. Treatment of CTM suppressed the MMP-9 and MMP-2 enzyme
      activities in the ATRA-induced invasion of the SH-SY5Y cells. To confirm the
      involvement of Tgase-2, gene silencing of Tgase-2 was performed in the ATRA
      induced invasion of the SH-SH5Y cells. The siRNA of Tgase-2 suppressed the MMP-9
      and MMP-2 activity of the SH-SY5Y cells. MMP-2 and MMP-9 are well known target
      genes of NF-kappaB. Therefore the relationship of Tgase-2 and NF-kappaB in the
      ATRA-induced invasion of the SH-SY5Y cells was examined using siRNA and CTM. ATRA
      induced the activation of NF-kappaB in the SH-SY5Y cells and CTM suppressed the
      activation of NF-kappaB. Gene silencing of Tgase-2 suppressed the MMP expression
      by ATRA. These results suggested that Tgase-2 might be a new target for
      controlling the ATRA-induced invasion of NBs. 

PMID- 24130926
TI  - The Changes of P-glycoprotein Activity by Interferon-gamma and Tumor Necrosis
      Factor-alpha in Primary and Immortalized Human Brain Microvascular Endothelial
      Cells.
AB  - The purpose of this study was to investigate the modification of expression and
      functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) at the blood-brain
      barrier (BBB). We used immortalized human brain microvessel endothelial cells
      (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in
      vitro BBB model. To investigate the change of p-gp expression, we carried out
      real time PCR analysis and Western blotting. To test the change of p-gp activity,
      we performed rhodamin123 (Rh123) accumulation study in the cells. In results of
      real time PCR analysis, the P-gp mRNA expression was increased by TNF-alpha or
      IFN-gamma treatment for 24 hr in both cell types. However, 48 hr treatment of TNF
      alpha or IFN-gamma did not affect P-gp mRNA expression. In addition, co-treatment
      of TNF-alpha and IFN-gamma markedly increased the P-gp mRNA expression in both
      cells. TNF-alpha or IFN-gamma did not influence P-gp protein expression whatever
      the concentration of cytokines or duration of treatment in both cells. However, P
      gp expression was increased after treatments of both cytokines together in iHBMEC
      cells only compared with untreated control. Furthermore, in both cell lines, TNF
      alpha or IFN-gamma induced significant decrease of P-gp activity for 24 hr
      treatment. And, both cytokines combination treatment also decreased significantly
      P-gp activity. These results suggest that P-gp expression and function at the BBB
      is modulated by TNF-alpha or/and IFN-gamma. Therefore, the distribution of P-gp
      depending drugs in the central nervous system can be modulated by neurological
      inflammatory diseases. 

PMID- 24130927
TI  - Isopsoralen Induces Differentiation of Prechondrogenic ATDC5 Cells via Activation
      of MAP Kinases and BMP-2 Signaling Pathways.
AB  - Endochondral bone formation is the process by which mesenchymal cells condense to
      become chondrocytes, which ultimately form new bone. The process of chondrogenic
      differentiation and hypertrophy is critical for bone formation and as such is
      regulated by many factors. In this study, we aimed to indentify novel factors
      that regulate chondrogenesis. We investigated the possible role of isopsoralen in
      induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5
      cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in
      a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were
      stained more intensely with Alcian blue than control cells, suggesting that
      isopsoralen increases the synthesis of matrix proteoglycans. Similarly,
      isopsoralen markedly induced the activation of alkaline phosphatase activity
      compared with control cells. Isopsoralen enhanced the expressions of chondrogenic
      marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time
      dependent manner. Furthermore, isopsoralen induced the activation of
      extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c
      jun N-terminal kinase (JNK). Isopsoralen significantly enhanced the protein
      expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors
      of ERK and p38 MAPK, respectively, decreased the number of stained cells treated
      with isopsoralen. Taken together, these results suggest that isopsoralen mediates
      a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore
      a possible therapeutic agent for bone growth disorders. 

PMID- 24130928
TI  - Effects of Resveratrol and trans-3,5,4'-Trimethoxystilbene on Glutamate-Induced
      Cytotoxicity, Heme Oxygenase-1, and Sirtuin 1 in HT22 Neuronal Cells.
AB  - Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention
      recently for the potential neuroprotective effects in neurodegenerative disorders
      where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising
      therapeutic targets. Resveratrol has been known to increase HO-1 expression and
      SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'
      trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by
      glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have
      been investigated by using murine hippocampal HT22 cells, which have been widely
      used as an in vitro model for investigating glutamate-induced neurotoxicity.
      Resveratrol protected HT22 neuronal cells from glutamateinduced cytotoxicity and
      increased HO-1 expression as well as SIRT1 activity in a concentration-dependent
      manner. Cytoprotec-tion afforded by resveratrol was partially reversed by the
      specific inhibition of HO-1 expression by HO-1 small interfering RNA and the
      nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1
      inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in
      lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog,
      failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase
      HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the
      cytoprotective effect of resveratrol was at least in part associated with HO-1
      expression but not with SIRT1 activation and, importantly, that the presence of
      hydroxyl groups on the benzene rings of resveratrol appears to be necessary for
      cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and
      SIRT1 activation in HT22 neuronal cells. 

PMID- 24130929
TI  - Anti-Cancer Effect of IN-2001 in MDA-MB-231 Human Breast Cancer.
AB  - In recent years, inhibition of HDACs has emerged as a potential strategy to
      reverse aberrant epigenetic changes associated with cancer, and several classes
      of HDAC inhibitors have been found to have potent and specific anticancer
      activities in preclinical studies. But their precise mechanism of action has not
      been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4
      dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its
      antitumor activity and the underlying molecular mechanisms of any such activity
      on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC
      activity (IC50 = 0.585 nM) in MDA-MB-231 human breast cancer cells. IN-2001
      caused a significant dose-dependent inhibition of cell proliferation in estrogen
      receptor (ER) negative MDA-MB-231 human breast cancer cells. Cell cycle analysis
      revealed that the gowth inhibitory effects of IN-2001 might be attributed to cell
      cycle arrest at G0/G1 and/or G2/Mphase and subsequent apoptosis in human breast
      cancer cells. These events are accompanied by modulating several cell cycle and
      apoptosis regulatory genes such as CDK inhibitors p21(WAF1) and p27(KIP1) cyclin
      D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001
      inhibited cell proliferation and induced apoptosis in human breast cancer cells
      and these findings may provide new therapeutic approaches, combination of
      antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER
      negative breast cancers. In summary, our data suggest that this histone
      deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with
      potent antitumor effects against human breast cancers. 

PMID- 24130930
TI  - Expression of recombinant rotavirus proteins harboring antigenic epitopes of the
      hepatitis a virus polyprotein in insect cells.
AB  - Rotavirus and hepatitis A virus (HAV) spread by the fecal-oral route and
      infections are important in public health, especially in developing countries.
      Here, two antigenic epitopes of the HAV polyprotein, domain 2 (D2) and domain 3
      (D3), were recombined with rotavirus VP7, generating D2/VP7 and D3/VP7, cloned in
      a baculovirus expression system, and expressed in Spodoptera frugiperda 9 (Sf9)
      insect cells. All were highly expressed, with peak expression 2 days post
      infection. Western blotting and ELISA revealed that two chimeric proteins were
      antigenic, but only D2/VP7 was immunogenic and elicited neutralizing antibody
      responses against rotavirus and HAV by neutralization assay, implicating D2/VP7
      as a multivalent subunit-vaccine Candidate for preventing both rotavirus and HAV
      infections. 

PMID- 24130931
TI  - Investigation into the Efficacy of Val-SN-38, a Valine-Ester Prodrug of the Anti
      Cancer Agent SN-38.
AB  - We recently reported that Val-SN-38, a novel valine ester prodrug of SN-38, had
      greatly improved the intracellular accumulation of SN-38 in MCF-7 cell line,
      probably through enhanced uptake via amino acid transporters. In the present
      study, the efficacy of Val-SN-38 was further investigated both in vitro and in
      vivo. It was found that the in vitro cytotoxic effect of Val-SN-38 was similar to
      that of SN-38. Moreover, Val-SN-38 exhibited an equal potency to that of SN-38 in
      survival experiments in vivo. Because these results seemed to be contrary to the
      previous finding, further investigation was performed to find out the underlying
      cause of the contradiction. As only the lactone form is known to have cytotoxic
      activity, the proportion of lactone in Val-SN-38 and SN-38 was determined, but no
      differences were found. However, it turned out that Val-SN-38 had poor stability
      compared with SN-38, which resulted in a decrease in beneficial efficacy for Val
      SN-38. Overall, the present study showed that a valine-added prodrug approach
      could be advantageous provided that the stability of the compound can be ensured.
      We believe this is a noteworthy study that unravels the discrepancy between
      intracellular accumulation and efficacy of valine-added prodrug. 

PMID- 24130932
TI  - A Comparison between Extract Products of Magnolia officinalis on Memory
      Impairment and Amyloidogenesis in a Transgenic Mouse Model of Alzheimer's
      Disease.
AB  - The components of Magnolia officinalis have well known to act anti-inflammatory,
      anti-oxidative and neuroprotective activities. These efficacies have been sold
      many products as nutritional supplement extracted from bark of Magnolia
      officinalis. Thus, to assess and compare neuroprotective effect in the
      nutritional supplement (Magnolia Extract(TM), Health Freedom Nutrition LLC, USA)
      and our ethanol extract of Magnolia officinalis (BioLand LTD, Korea), we
      investigated memorial improving and anti-Alzheimer's disease effects of extract
      products of Magnolia officinalis in a transgenic AD mice model. Oral pretreatment
      of two extract products of Magnolia officinalis (10 mg/kg/day in 0.05% ethanol)
      into drinking water for 3 months ameliorated memorial dysfunction and prevented
      Abeta accumulation in the brain of Tg2576 mice. In addition, extract products of
      Magnolia officinalis also decreased expression of beta-site APP cleaving enzyme 1
      (BACE1), amyloid precursor protein (APP) and its product, C99. Although both two
      extract products of Magnolia officinalis could show preventive effect of memorial
      dysfunction and Abeta accumulation, our ethanol extract of Magnolia officinalis
      (BioLand LTD, Korea) could be more effective than Magnolia Extract(TM) (Health
      Freedom Nutrition LLC, USA). Therefore, our results showed that extract products
      of Magnolia officinalis were effective for prevention and treatment of AD through
      memorial improving and anti-amyloidogenic effects via down-regulating beta
      secretase activity, and neuroprotective efficacy of Magnolia extracts could be
      differed by cultivating area and manufacturing methods. 

PMID- 24130933
TI  - Sarsasapogenin Increases Melanin Synthesis via Induction of Tyrosinase and
      Microphthalmia-Associated Transcription Factor Expression in Melan-a Cells.
AB  - Sarsasapogenin (SAR) is a steroidal sapogenin that is used as starting material
      for the industrial synthesis of steroids. It has various pharmacological
      benefits, such as antitumor and antidepressant activities. Since its effect on
      melanin biosynthesis has not been reported, we used murine melanocyte melan-a
      cells to investigate whether SAR influences melanogenesis. In this study, SAR
      significantly increased the melanin content of the melan-a cells from 1 to 10
      MUM. Based on an enzymatic activity assay using melan-a cell lysate, SAR had no
      effect on tyrosinase and DOPAchrome tautomerase activities. It also did not
      affect the protein expression of tyrosinase-related protein 1 and DOPAchrome
      tautomerase. However, protein levels of tyrosinase and microphthalmia-associated
      transcription factor were strongly stimulated by treatment with SAR. Therefore,
      our reports suggest that SAR treatment may induce melanogenesis through the
      stimulation of tyrosinase and microphthalmia-associated transcription factor
      expression in melan-a cells. 

PMID- 24130934
TI  - Combined effects of multiple endoplasmic reticulum stresses on cytokine secretion
      in macrophage.
AB  - Cells show various stress signs when they are challenged with severe
      physiological problems. Majority of such cellular stresses are conveyed to
      endoplasmic reticulum (ER) and unfolded protein response (UPR) serves as typical
      defense mechanism against ER stress. This study investigated an interaction
      between ER stress agents using macropage cell line Raw 264.7. When activated by
      lipopolysaccharide (LPS), the cell lines showed typical indicators of ER stress.
      Along with molecular chaperones, the activation process leads to the production
      of additional infl ammatory mediators. Following activation, the macrophage cell
      line was further treated with TUN and characterized in terms of chaperone
      expression and cytokine secretion. When treated with TUN, the activated
      macrophage cell leads to increased secretion of IL-6 although expression of ER
      stress markers, GRP94 and GRP78 increased. The secretion of cytokines continued
      until the addition of BFA which inhibits protein targeting from ER to Golgi.
      However, secretion of cytokines was ceased upon dual treatments with BFA and TG.
      This result strongly implies that cells may differently deal with various
      polypeptides depending on the urgency in cellular function under ER stress.
      Considering IL-6 is one of the most important signal molecules in macrophage, the
      molecule might be able to circumvent ER stress and UPR to reach its targeting
      site. 

PMID- 24130935
TI  - Controversial effect of ethanol irrespective of kinases inhibition on the agonist
      dependant vasoconstriction.
AB  - The present study was undertaken to determine whether ethanol influences on the
      agonist-induced vascular smooth muscle contraction and, if so, to investigate the
      related mechanism. The measurement of isometric contractions using a computerized
      data acquisition system was combined with molecular experiments. Ethanol
      significantly inhibited thromboxane A2 mimetic-induced contraction with intact
      endothelial function, but there was no relaxation on thromboxane A2 mimetic U
      46619-induced contraction irrespective of endothelium suggesting that the pathway
      such as Rho-kinase activation, Ca(2+) entry or thin filament regulation was not
      affected. In addition, ethanol didn't decrease thromboxane A2 mimetic-induced
      increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or
      pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester
      induced contraction in denuded muscles suggesting that thin filament regulation
      is less important on the ethanol-induced regulation in the muscle than
      endothelial NO synthesis. In conclusion, this study provides the evidence and
      possible related mechanism concerning the effect of ethanol on the agonist
      dependent contraction in rat aortic rings with regard to endothelial function. 

PMID- 24130937
TI  - Health science and technology evaluation: emerging for innovation.

PMID- 24130936
TI  - The system of care for the diabetic foot: objectives, outcomes, and
      opportunities.
AB  - Most cases of lower extremity limb loss in the United States occur among people
      with diabetes who have a diabetic foot ulcer (DFU). These DFUs and the associated
      limb loss that may occur lead to excess healthcare costs and have a large
      negative impact on mobility, psychosocial well-being, and quality of life. The
      strategies for DFU prevention and management are evolving, but the implementation
      of these prevention and management strategies remains challenging. Barriers to
      implementation include poor access to primary medical care; patient beliefs and
      lack of adherence to medical advice; delays in DFU recognition; limited
      healthcare resources and practice heterogeneity of specialists. Herein, we review
      the contemporary outcomes of DFU prevention and management to provide a framework
      for prioritizing quality improvement efforts within a resource-limited healthcare
      environment. 

PMID- 24130939
TI  - Pathologic analysis of control plans for air pollution management in tehran
      metropolis: a qualitative study.
AB  - BACKGROUND: Regarding the importance of air pollution issue for large cities, as
      Tehran metropolis, many plans, programs, projects and regulations have been
      developed to manage urban air pollution. However, most of them failed to decline
      the pollution. The purpose of this study is to pathologically analyze air
      pollution control plans in order to offer effective solutions for Tehran
      metropolis. METHODS: A qualitative content analysis and a semi-structured
      interview with 14 practicing professionals were used to identify key causes and
      sources of Tehran's air pollution, to recognize challenges and obstacles towards
      effective performance of air-pollution control plans in this metropolitan area,
      and to suggest the most effective controlling solutions. RESULTS: Challenges
      related to air-pollution control plans can be divided into two major categories:
      Firstly lack of integrated and organized stewardship and secondly those related
      to political, economical, social and technical environmental abbreviated as PEST,
      challenges. For effective control of the Tehran air pollution, the following
      eight controlling alternatives were identified: Systematization of plan
      preparation process, organizing the stewardship, standardization and utilization
      of new technologies and professional experts, cultural and infrastructural
      development, realization of social justice, developing coordination and
      controlling mechanisms, improving citizen's participatory capacity, and focusing
      on effective management of fuel and energy. CONCLUSIONS: Controlling air
      pollution in Tehran should be considered as a priority for policymakers to make
      enforcements through applying a systemic cycle of preparation effective and
      comprehensive plans. Further, implement the enforcements and evaluate the
      environmental impact of the plans through involving all stakeholders.

PMID- 24130938
TI  - Essentials of periodontal medicine in preventive medicine.
AB  - Influence of systemic disorders on periodontal diseases is well established.
      However, of growing interest is the effect of periodontal diseases on numerous
      systemic diseases or conditions like cardiovascular disease, cerebrovascular
      disease, diabetes, pre-term low birth weight babies, preeclampsia, respiratory
      infections and others including osteoporosis, cancer, rheumatoid arthritis,
      erectile dysfunction, Alzheimer's disease, gastrointestinal disease, prostatitis,
      renal diseases, which has also been scientifically validated. This side of the
      oral-systemic link has been termed Periodontal Medicine and is potentially of
      great public health significance, as periodontal disease is largely preventable
      and in many instances readily treatable, hence, providing many new opportunities
      for preventing and improving prognosis of several systemic pathologic conditions.
      This review article highlights the importance of prevention and treatment of
      periodontal diseases as an essential part of preventive medicine to circumvent
      its deleterious effects on general health. 

PMID- 24130940
TI  - The role of lupus nephritis in development of adverse maternal and fetal outcomes
      during pregnancy.
AB  - BACKGROUND: We aimed to investigate the relationship of lupus nephritis (LN) with
      fetal and maternal outcomes of pregnant patients with systemic lupus
      erythematosus (SLE). METHODS: In a retrospective study, profiles of pregnant
      women with SLE were selected. Before pregnancy and at the end of first, second
      and third trimesters, SLE disease activity index-2K was assessed. Clinical and
      laboratory evaluations were carried out regularly. Maternal and fetal outcomes
      were recorded. Assessments of the crude effects of statistically significant
      variables on pregnancy outcomes were performed through multivariate regression
      analysis. RESULTS: 72 pregnancies in 65 patients were recorded. The mean age of
      LN patients was 28.7 years, whereas the mean age of patients with clinical
      nephritis was 26.1 years. No woman with LN experienced pre-term labor or
      stillbirth. 16 pregnancies either ended in abortion or experienced preeclampsia
      of which seven had LN. Multivariate logistic regression analyses showed that LN
      and positive antinuclear antibody were related to preeclampsia, whereas age of
      SLE development was associated with pre-term labor. Combined maternal and fetal
      outcomes were associated with the past history of abortion and LN. LN was
      associated with preeclampsia and SLE flare. CONCLUSIONS: Absence of LN was in
      favor of prevention of SLE flare and preeclampsia.

PMID- 24130941
TI  - Association between Physical Activity and Metabolic Risk Factors in Adolescents:
      Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Physical activity (PA) is associated with the metabolic syndrome
      (MetS) and its components. This study aimed to examine the association between PA
      and MetS and its components among normal weight and overweight/obese adolescent
      in Tehran Lipid and Glucose Study (TLGS). METHODS: This cross-sectional study
      includes 777 adolescents, aged 12-18 years, who were selected by multi-stage
      random cluster sampling from among TLGS participants. Subjects were classified as
      normal weight and overweight/obese based on the age- and sex-specific
      standardized percentile curves of BMI for Iranian population. Levels of PA were
      assessed using a standardized and modifiable activity questionnaire (MAQ), and
      categorized into tertiles. MetS was defined according to the Cook's criteria.
      RESULTS: Prevalence of the MetS was higher in overweight/obese than normal group
      (35% vs. 3%; P: 0.02). Normal groups were more physically active (50% vs. 44%);
      however, difference was not significant. There was a significant association
      between the light PA and risk of lower level of HDL-C before and after
      adjustment, in normal weight group (OR: 1.61, CI 95%: 1.11, 2.35; OR: 1.65, CI
      95%: 1.12, 2.44, respectively). The overweight/obese group with light and
      moderate PA had a higher risk of having abdominal obesity than those with
      vigorous PA, only after adjustment for determined covariates (OR: 1.11, CI 95%:
      1.07, 1.21; OR: 1.06, CI 95%: 1.01, 1.08, respectively); the association between
      MetS and PA was not significant. CONCLUSIONS: The results of this study confirm
      the association between PA and some individual components of MetS such as waist
      and HDL-C.

PMID- 24130942
TI  - Food Insecurity Status and Associated Factors among Rural Households in North
      East of Iran.
AB  - BACKGROUND: To assess the prevalence of food insecurity and associated factors
      among rural households in north-east of Iran. METHODS: In this cross-sectional
      study, a total of 4647 rural households (18,061 persons) were studied in
      Neyshabur, a city in north-east of Iran. The Iranian version of the Six-Item
      Short questionnaire of Household Food Security Scale was used to measure food
      insecurity. Logistic regression model was used to estimate odds ratios (OR) and
      95% confidence intervals (CI). RESULTS: Total prevalence of food insecurity in
      this study was 40.9% (95% CI 39.49-42.31). Backward Multivariate Logistic
      Regression model showed that OR of food insecurity increased with: The presence
      of chronic disease in household in comparison the absence (OR = 2.02), the rural
      distance >30 km from the city in comparison the distance <=30 km (OR = 1.41), the
      presence of smoker in household in comparison the absence (OR = 1.8), the
      residential infrastructure of household <=50 m(2) in comparison the >50 m(2) (OR
      = 1.57), the presence of single parent in comparison the presence of both parents
      at home (OR = 1.38) and the household income (per month) <4,000,000 Rial in
      comparison the >=4,000,000 Rial (OR = 3.91). But OR of food insecurity decreased
      with having a car in family in comparison not having (OR = 0.54) and the family
      having a house in comparison not having (OR = 0.61). CONCLUSIONS: According to
      results of this study, food insecurity is prevalent among rural households of
      Neyshabur, so it is an important public health problem in this region.

PMID- 24130943
TI  - Use of Glycated Hemoglobin in the Diagnosis of Diabetes Mellitus and Pre-diabetes
      and Role of Fasting Plasma Glucose, Oral Glucose Tolerance Test.
AB  - BACKGROUND: A highly standardized screening test for newly diagnosis diabetes and
      pre-diabetes is necessary. the study goal was to clarify the power and efficacy
      of glycated hemoglobin (HbA1c) in the diagnosis of diabetes and pre-diabetes by
      comparing against the other American Diabetes Association (ADA) diagnostic
      criteria of fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT).
      METHODS: This is a retrospective study. A total of 27,001 individuals attended to
      the internal medicine outpatient clinic between 2006 and 2010 years were
      screened. All diabetic patients and those using drugs associated with the
      development of diabetes were excluded. The results of FPG, OGTT and HbA1c for
      1814 individual were analyzed and all grouped as diabetic patients, glucose
      intolerant (pre-diabetes) patients and non-diabetic patients according to new ADA
      criteria for the diagnosis of diabetes. RESULTS: The prevalence of newly
      diagnosed diabetes was 69.6% and 54% by using HbA1c alone, 64.2% and 28.2% with 2
      h OGTT alone and 43.2% and 60.3%, respectively with FPG alone. Differences
      between FPG versus 2-h OGTT, FPG versus A1c and OGTT versus A1c were
      statistically significant (P < 0.0001, P < 0.0001 and P = 0.02, respectively).
      Diagnostic sensitivity of all diabetic criteria was 69.6% for A1c; Nearly, 64.2%
      for OGTT and only 43.1% for FPG respectively. In terms of diagnostic ratio of
      glucose intolerance; difference between HbA1C and OGTT was statistically
      significant (P < 0.0001). CONCLUSIONS: As a screening tool for newly diagnosed
      diabetes and pre-diabetes, the HbA1C level performed better than FPG and 2-h OGTT
      in this general Saudi population. High diagnostic power of A1C may contribute to
      the decrease in the number of undiagnosed patients.

PMID- 24130944
TI  - Respiratory Tract Infections and its Preventive Measures among Hajj Pilgrims,
      2010: A Nested Case Control Study.
AB  - BACKGROUND: Respiratory tract infections are very common among the Hajj pilgrims.
      Some preventive measures including Influenza vaccination, using face mask and
      salt water gargling have been considered to control these infections and the
      reports show conflicting results about the effects of each one of these measures.
      This study is trying to assess the effects of these recommendations on
      respiratory tract infections. METHODS: According to nested case-control design,
      in a cohort consisting of 338 Iranian pilgrims, the outcome examined, was all
      types of respiratory tract infections other than common colds. With occurrence of
      any patient in convoy, data collection form was completed for that person. On the
      same day, two people were randomly selected as control group from among pilgrims
      who have not affected so far. RESULTS: During Hajj, 32 pilgrims (9.5%) were
      affected by respiratory tract infections other than common colds. In univariable
      logistic regression analysis, salt water gargling (OR = 2.4, P = 0.08), existence
      of other patient in the room (OR = 2.14, P = 0.19), age over 60 years (OR = 1.84,
      P = 0.15) and the education more than or equal to 3 years (OR = 1.93, P = 0.16)
      were effective in the respiratory tract infections (P < 0.2). However,
      multivariable logistic regression analysis showed that none of the above
      mentioned factors are significantly associated with these infections.
      CONCLUSIONS: This study showed that measures such as seasonal influenza
      vaccination, use of face masks and personal prayer carpet have no effect on the
      incidence of respiratory tract infections. However, washing throat and mouth with
      salt water can be considered the most effective preventive measures.

PMID- 24130945
TI  - Disease surveillance and private sector in the metropolitans: a troublesome
      collaboration.
AB  - BACKGROUND: An effective response to health problems is completely dependent upon
      the capacities of the health system in providing timely and valid information to
      take action. This study was designed to identify various reasons from various
      perspectives for underreporting disease by physicians in the private sector in
      big cities in developing countries setting. METHODS: In this qualitative study,
      we used focus group discussions (16 manager), and in-depth semi-structured
      interviews. RESULTS: Themes were classified in 6 categories: Infrastructure and
      legal issues, the priority of disease reporting, workflow processes, motivation
      and attitude, human resources and knowledge and awareness. As the main reasons of
      under reporting, most physicians pointed out complicacy in reporting process and
      inadequate attention by the public sector. Managers emphasized instituting legal
      incentives and penalties. Experts focused on physicians' knowledge and expressed
      a need for continuing medical education programs. CONCLUSIONS: Independent
      interventions will have little chance of success and sustainability. Different
      intervention programs should consider legal issues, attitude and knowledge of
      physicians in the private sector, and building a simple reporting process for
      physicians. Intervention programs in which the reporting process offers
      incentives for all stakeholders can help improving and sustaining the disease
      reporting system.

PMID- 24130946
TI  - The Effects of Panax Ginseng on Lipid Profile, Pro-oxidant: Antioxidant Status
      and High-sensitivity C Reactive Protein Levels in Hyperlipidemic Patients in
      Iran.
AB  - BACKGROUND: Because of the conflicting results from previous studies regarding
      the efficacy of ginseng on lipid profile and anti-inflammatory and anti
      proliferative activities of its components, we aimed to evaluate the effects of
      Panax ginseng on lipid profile, pro-oxidant - anti-oxidant status and high
      sensitivity C reactive protein (hs-CRP) levels. METHODS: Forty Iranian
      hyperlipidemic patients were randomly assigned to placebo (n = 20) or control (n
      = 20) groups in this double-blind randomized controlled trial. The ginseng or
      placebo was taken two capsules twice a day for 8 weeks. Total cholesterol (TC),
      triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C), fasting blood glucose, serum creatinine and hs
      CRP levels and pro-oxidant - anti-oxidant balance (PAB) were estimated before and
      after intervention. RESULTS: There were no significant differences between the
      two groups with respect to changes in serum TG, LDL-C, HDL-C, and TC/HDL-C
      levels. Nor were there significant differences between the two groups with
      respect to changes in hs-CRP level and PAB from baseline to week 8. CONCLUSIONS:
      Our study demonstrates that ginseng does not have significant effects on lipid
      profile, Hs-CRP level and PAB. Further clinical studies, with a larger sample
      size, more prolonged period of therapy are needed to investigate the therapeutic
      effects of ginseng.

PMID- 24130947
TI  - Factor Structure of the World Health Organization's Quality of Life Questionnaire
      BREF in Patients with Coronary Artery Disease.
AB  - BACKGROUND: The World Health Organization Quality of Life Questionnaire (WHOQOL)
      BREF is one of the most known general questionnaires for assessment of quality of
      life (QOL) in both healthy populations and in various diseases subgroups. The aim
      of the present study was to examine the construct validity of this questionnaire
      in patients with coronary artery disease (CAD) using factor analysis. METHODS:
      Two hundred and seventy-five patients aged 35-80 years old with the diagnosis of
      CAD admitted to the Tehran Heart Center operating room for coronary artery bypass
      were consecutively entered into the study. QOL was assessed using the WHOQOL
      BREF. To estimate the reliability of the QOL questionnaire, Cronbach's a
      coefficient was measured. To assess the structure of the questionnaire, we
      firstly performed confirmatory factor analysis to test the hypothesized factor
      models. Exploratory factor analysis was then performed using the principal
      component method with varimax rotation. RESULTS: Reliability of the questionnaire
      was low (Cronbach's a for different domains ranged from 0.24 to 0.74). In
      confirmatory factor analysis, only the 1-factor model indicated a good fit to the
      data. The exploratory factor analysis indicated a five-factor solution that
      jointly accounted for 55.7% of the variance observed. Also, the pattern of item
      loading was very different from the original structure of the questionnaire.
      CONCLUSIONS: The findings suggest that the WHOQOL-BREF might only be a measure of
      the overall QOL in patients with CAD, and is not a suitable instrument for
      measuring the different QOL dimensions as expected in this population.

PMID- 24130948
TI  - Olive and sesame oil effect on lipid profile in hypercholesterolemic patients,
      which better?
AB  - BACKGROUND: The study on natural substances especially, dietary components such
      as liquid oils affecting cholesterol can be important for therapeutic propose.
      Sesame seeds with various biomedical actions can be control the
      hypercholesterolemia. On the other hand, olive oil has a wide range of
      therapeutic effect on lipid profile in human. The aim of this study is to
      evaluate and compare lipid profile changes after olive and sesame oils
      consumption in hypercholesterolemia. METHODS: This study was a clinical
      randomized trial that was performed via parallel design on 48 patients. The
      patients were randomly allocated in to two groups: A: olive oil and B: sesame
      oil. After 1 month prescription of Step I National Cholesterol Education Program
      diet, patients consumed 4 table spoons aprox. 60 g) of refined olive or sesame
      oil daily as an exchange of other oils, for 1 month. Lipid profiles The P < 0.05
      was considered as significant difference. RESULTS: Out of 48 patients, 24 (50%)
      were men. The mean age was 41.7 +/- 8.3 years. The mean of total cholesterol,
      triglyceride (TG), low density lipoprotein (LDL), cholesterol, and high density
      lipoprotein (HDL) cholesterol, before oil consumption was 224.5 +/- 22, 256 +/-
      132, 132.6 +/- 9, and 44.5 +/- 11 mg/dl. After olive oil consumption cholesterol,
      TG, LDL-C, weight, waist and BMI were decreased and HDL-C was increased. After
      sesame oil consumption cholesterol, TG, LDL-C were significantly decreased.
      Weight, waist were decreased and HDL-C was increased (P > 0.05). CONCLUSIONS:
      Sesame oil had equivalent effect on lipid profile in comparison olive oil and
      lipid profile improvement was better in sesame oil in LDL-C and TG.

PMID- 24130949
TI  - Sensitivity of palm print, modified mallampati score and 3-3-2 rule in prediction
      of difficult intubation.
AB  - BACKGROUND: This study evaluated the performance of modified Mallampati score, 3
      3-2 rule and palm print in prediction of difficult intubation. METHODS: In a
      prospective descriptive study, data from 500 patients scheduled for elective
      surgery under general anesthesia were collected. An anesthesiologist evaluated
      the airway using mentioned tests and another anesthesiologist evaluated difficult
      intubation. Laryngoscopic views were determined by Cormack and Lehane score.
      Grades 3 and 4 were defined as difficult intubation. Sensitivity, specificity,
      positive predictive value, negative predictive value and Youden index were
      determined for all tests. RESULTS: Difficult intubation was reported in 8.9% of
      the patients. There was a significant correlation between body mass index and
      difficult intubation (P : 0.004); however, other demographic characteristics
      didn't have a significant correlation with difficult intubation. Among three
      tests, palm print was of highest specificity (96.46%) and modified Mallampati of
      highest sensitivity (98.40%). In a combination of the tests, the highest
      specificity, sensitivity and Youden index were observed when using all three
      tests together. CONCLUSIONS: Palm print has a high specificity for prediction of
      difficult intubation, but the best way for prediction of difficult intubation is
      using all three tests together.

PMID- 24130950
TI  - Overweight and obesity among early adolescent school girls in urban area of west
      bengal, India: prevalence assessment using different reference standards.
AB  - BACKGROUND: Overweight and obesity are epidemic and a 'public health crisis'
      among adolescents worldwide. The rising trends in adolescent obesity in girl are
      poorly documented in India. The aim of this study was to compare and assess the
      extent of overweight and obesity in early adolescent school girls using three
      references [World Health Organization (WHO) 2007; the Center for Diseases Control
      (CDC) 2000 and the International Obesity Task Force (IOTF) 2000]. METHODS: A
      cross sectional study was designed in 1375 early adolescent girl (10-14 years),
      in five Government affiliated schools of Kharagpur Municipality of West Bengal,
      India. RESULTS: Results of this study are eloquent of the fact that the roots of
      obesity lies in early stage of adolescence. Incidence of overweight, including
      obesity of participants was 10.62%, 7.64% and 7.49% depending on the references
      used (WHO, CDC and IOTF) respectively. Both incidence and remission rates were
      higher among younger girls. CONCLUSIONS: Regarding the harmful ramifications of
      overweight and obesity, it is encourage to healthy eating patterns and increase
      physical activity among early adolescent girls.

PMID- 24130951
TI  - First Iranian imported case of dengue.
AB  - Dengue fever, a mosquito-borne flavivirus infection, is endemic in Southeast
      Asia. Currently, incidences have been increasing among adults. There have been no
      published reports of dengue fever from Iran. Widespread connection between
      different countries may predispose them for acquisition of infection. The patient
      was a 58-year-old Iranian woman with acute unexplained high-grade fever for 4
      days, associated with skin rash, after returning from Southeast Asia. CBC showed
      WBC = 1600/mm(3) and platelet count 99,000/mm(3). The patient also had hematuria.
      ELISA immunoglobulin M (IgM) antibodies to dengue and serum RT-PCR for dengue
      virus was positive. The patient managed with conservative treatment and due to
      good general condition and improvement specific antiviral treatment was not
      started. She became afebrile at the 3(rd) day of hospitalization and discharged
      with good general condition on fourth day. She was afebrile after two weeks
      follow-up. Dengue fever has been increasing among adults. It should be suspected,
      when a patient presents with acute febrile illness and skin rashes returning from
      endemic region. Conservative treatment may be conducted in uncomplicated cases. 

PMID- 24130952
TI  - Changing the Treatment of Permanent Neonatal Diabetes Mellitus from Insulin to
      Glibenclamide in a 4-Month-Old Infant with KCNJ11 Activating Mutation.
AB  - Permanent neonatal diabetes mellitus (PNDM) is a rare type of diabetes and KCNJ11
      gene activating mutation is one of its prevalent causes. We introduced a 4-month
      old male infant with poor feeding, restlessness, tachypnea, hyperglycemia,
      metabolic acidosis, and ketonemia. He was discharged with insulin and after 2
      months, KCNJ11 gene mutation was found and treatment was switched from
      subcutaneous insulin to oral glibenclamide. Now, he is 1 year old with desirable
      glycemic control; therefore, genetic study is recommended for KCNJ11 gene
      mutation in such patients because if the mutation is found, treatment can be
      switched from insulin to sulfonylurea. 

PMID- 24130953
TI  - Assessment of clinical profile of the patients treated at ayurvedic health
      facilities in north India.
AB  - Since a very long time, a significant number of patients have been seeking
      treatment at Complementary and Alternative Medicine health facilities, but the
      disease burden at these facilities has never been assessed and documented.
      Present cross-sectional study was carried out at Ayurvedic tertiary care hospital
      to document and to assess the rationale of disease reporting at Ayurvedic
      institutions of the northern state of India from January 2011 to October 2011.
      Almost half of the patients' morbidities were not classified at all into any of
      the disease categories. The common reported morbidities at study hospital were:
      Respiratory (10.5%), neuromuscular (9.5%), digestive (9.2%) and circulatory
      (9.1%) disorders. As the majority of diseases were unclassified, so mainstreaming
      of the effective disease surveillance would be required to understand the
      morbidity pattern and successful treatment practices at health facilities. 

PMID- 24130954
TI  - Role of private-public partnership in health education: a survey of current
      practices in udaipur city, rajasthan, India.
AB  - BACKGROUND: The concept of a public-private partnership (PPP) has been proposed
      as a potential model for providing education services besides public finance and
      public delivery. The present study was conducted to survey the current practices
      of Private-Public Partnership (PPP) in health education in Udaipur city,
      Rajasthan, India. METHODS: A questionnaire survey was conducted among
      organizations involved exclusively and actively in health education in Udaipur
      city, Rajasthan, India. The pretested self designed structured questionnaire
      consisted of 21 items pertaining to the current practices of private-public
      partnership (PPP) in health education. Descriptive statistics were used to
      describe the data. RESULTS: On the basis of inclusion criteria, 50 personnel from
      2 private dental colleges, 1 private medical college, 2 Non Government
      Organizations (NGOs) and 1 health museum were selected. Only 15 (30%) of
      participants agreed that they have a written reference policy that outlines the
      services they provide to the general public. Regarding the collection of health
      education materials available, majority 35 (70%) had printed books followed by
      audio visual (AV) materials (slides, videos, audio cassettes) [22 (44%)]. 35
      (70%) of participants reported that they loan only pamphlets and broachers to the
      public. Thirty four (68%) of participants provide information about oral health.
      Only 23 (46%) of participants reported that their institution/organization
      undergo periodic evaluation. CONCLUSIONS: Results of this survey show that that
      most of the PPP were involved in delivering health education, mostly concentrated
      on general health. Only few of them were involved in oral health education. The
      role of PPP in health education is integral to the effort of promoting a
      healthier population. This effort continues the trend and broadens the scope of
      involvement for further studies.

PMID- 24130955
TI  - Sleep quality of professional firefighters.
AB  - BACKGROUND: Firefighting is a unique job with contradictious demands that expose
      firefighters to many well documented causal factors of sleep debt, but no studies
      in Iran and only a few worldwide studies have investigated their sleep quality
      while sleep problems may lead to catastrophes especially in critical service
      workers. The aim of this study is to evaluate sleep quality and its related
      factors among a sample of professional Iranian firefighters. METHODS: Using
      simple random sampling method in a cross-sectional study, 427 personnel of fire
      and rescue service were invited. They completed the Persian version of Pittsburgh
      Sleep Quality Index (PSQI) and a data collection sheet about their demographic
      and occupational features during an individual face to face interview in central
      office and firehouses throughout Tehran. Response rate was 88.7%. RESULTS: The
      mean +/- SD global PSQI score was 7.97 +/- 3.77. Sleep latency was the component
      of PSQI with the greatest degree of abnormality. 69.9% of participants were poor
      sleepers. Interestingly, we found no significant differences between sleep
      quality of shift workers and non shift workers. Using multiple logistic
      regression analysis, only having another job, smoking and years of job experience
      were predictors of poor sleep. CONCLUSIONS: In comparison with adult population
      of Tehran, sleep quality deterioration is notably more common in Tehran
      firefighters which require health promotion interventions to prevent its serious
      adverse outcomes.

PMID- 24130956
TI  - Oxidative stress and aging prevention.

PMID- 24130957
TI  - Effect of facial expressions on student's comprehension recognition in virtual
      educational environments.
AB  - The scope of this research is to examine whether facial expression of the
      students is a tool for the lecturer to interpret comprehension level of students
      in virtual classroom and also to identify the impact of facial expressions during
      lecture and the level of comprehension shown by these expressions. Our goal is to
      identify physical behaviours of the face that are linked to emotional states, and
      then to identify how these emotional states are linked to student's
      comprehension. In this work, the effectiveness of a student's facial expressions
      in non-verbal communication in a virtual pedagogical environment was investigated
      first. Next, the specific elements of learner's behaviour for the different
      emotional states and the relevant facial expressions signaled by the action units
      were interpreted. Finally, it focused on finding the impact of the relevant
      facial expression on the student's comprehension. Experimentation was done
      through survey, which involves quantitative observations of the lecturers in the
      classroom in which the behaviours of students were recorded and statistically
      analyzed. The result shows that facial expression is the most frequently used
      nonverbal communication mode by the students in the virtual classroom and facial
      expressions of the students are significantly correlated to their emotions which
      helps to recognize their comprehension towards the lecture. 

PMID- 24130958
TI  - Retrieval of HPV oncogenes E6 and E7 mRNA from cervical specimens using a manual
      open technology protocol.
AB  - BACKGROUND: HPV oncogenes mRNA detection gains momentum as an adjuvant for HPV
      related cervical abnormalities diagnosis, but is based on costly detection assays
      not allowing viral type targeting. OBJECTIVE: To assess detection rate of HPV
      oncogenes E6/E7 mRNA from cervical specimens using a manual, open technology,
      fully customizable protocol and determine whether HPV-related epidemiological
      features influence mRNA retrieval. We reviewed literature and compared our
      retrieval rate with automated technologies. METHODS: We used 60 samples positive
      for HPV DNA types 16, 18, 31 and/or 45. We extracted mRNA with a TRizol-based
      protocol, and tested mRNA purity and concentration using light absorbance. We
      reverse-transcribed mRNA into cDNA for E6/7 detection. RESULTS: HPV oncogenes
      E6/E7 mRNA was retrieved from 36 (60%) out of 60 specimens. No HPV load-related
      clinical or epidemiological feature was significantly associated with mRNA
      retrieval. Presence of HPV-DNA 16/18 was associated with mRNA retrieval (OR =
      9.08; 95% CI 1.26 to 65.32 for HPV 16; and 18.2; IC95% 1.86 to 391.44 for HPV
      18). CONCLUSIONS: The open-technology protocol yielded an mRNA detection rate
      similar to that of automated technologies. Advantages are lower costs and target
      HPV type customization.

PMID- 24130959
TI  - Identification of thermo tolerant lactic acid bacteria isolated from silage
      prepared in the hot and humid climate of Southwestern Japan.
AB  - To develop high-quality silage starters adapted to hot and humid weather, 12 LAB
      isolates from silage produced in Kyushu and Okinawa, Japan were characterized
      based on their morphological features, growth curves and sugar utilization. In
      addition, the nucleotide sequences of the V2-V3 region of their 16S rRNA genes
      and the 16S-23S rRNA intergenic spacer (ITS) regions were determined. The
      isolates were also subjected to RAPD-PCR analysis, DNA-DNA hybridization, G+C
      content analysis and immuno-identification using species-specific monoclonal
      antibodies and SDS-PAGE profiling. Nearly all of the isolates exhibited high
      thermotolerance and rapid growth. Combining ITS sequence analysis, RAPD-PCR and
      immuno-identification enabled rapid and accurate identification of closely
      related LAB strains that other methods failed to appropriately differentiate; for
      example, L. plantarum was distinguished from L. pentosus, and L. casei was
      distinguished from L. rhamonsus. Using the aforementioned techniques, the
      isolated strains were identified as L. plantarum, L. rhamonsus, L. rapi,
      Pediococcus pentosaceus and P. lolii. Our findings also showed that there is
      greater diversity among thermophilic LABs in silage prepared in a hot and humid
      environment. 

PMID- 24130960
TI  - Evaluation of sweet potato for fuel bioethanol production: hydrolysis and
      fermentation.
AB  - The enzymatic starch hydrolysis and bioethanol production from a variety of sweet
      potato developed for bioenergy purposes (K 9807.1) on the basis of its high
      starch yields, was studied. Drying at 55 degrees C and 95 degrees C of sweet
      potato neither affected the sugar content nor the starch enzymatic hydrolysis
      efficiency. Simultaneous saccharification and ethanol fermentations for dry
      matter ratio of sweet potato to water from 1:8 to 1:2 (w/v) were studied. Fresh
      sweet potato and dried at 55 degrees C (flour) were assayed. At ratios of 1:8,
      similar results for fresh sweet potato and flour in terms of ethanol
      concentration (38-45 g/L), fermentation time (16 h) and sugar conversion (~ 100%)
      were found. At higher dry matter content, faster full conversion were observed
      using flour. A higher ratio than that for fresh sweet potato (1:2.2) did not
      improve the final ethanol concentration (100 g/L) and yields. High ethanol yields
      were found for VHG (very high gravity) conditions. The sweet potato used is an
      attractive raw matter for fuel ethanol, since up to 4800 L ethanol per hectare
      can be obtained. 

PMID- 24130961
TI  - Molecular cloning and development of RAPD-SCAR markers for Dimocarpus longan
      variety authentication.
AB  - As an edible fruit and source of traditional medicine, D. longan is grown in most
      areas of Southern China. Identification of D. longan cultivars by using molecular
      markers is important genetically. In this study, we cloned fragments from
      improved randomly amplified polymorphic DNA (RAPD), and developed stably
      diagnostic sequence-characterized amplified region (SCAR) markers. The specific
      RAPD bands of D. longan cultivars from Guangxi, with size ranging from 500 bp to
      900 bp were gel-purified, cloned and sequenced. Four clones named LY2-1, LY4-7,
      LY4-8 and LY5-2 were identified. In order to investigate whether the fragments
      were specific for the species, four pairs of SCAR primers were then designed. PCR
      amplifications were conducted to analyze 18 samples including different D. longan
      cultivars and other species. The specific bands with expected sizes were
      amplified in five D. longan samples but not in others. To identify and
      characterize the difference between D. longan and D. confinis, PCR amplifications
      were performed again. The specific bands with expected sizes were found in D.
      longan but not in D. confinis by SCAR markers LY2-1, LY4-7 and LY5-2,
      respectively. These results showed that our developed SCAR markers could be very
      useful as a specific D. longan variety authentication. Therefore, our study
      provides an effective and precise PCR-based diagnostic method and markers to
      identify D. longan species. 

PMID- 24130962
TI  - Phytochemical analysis, antimicrobial and radical-scavenging properties of
      Acalypha manniana leaves.
AB  - Acalypha manniana (Euphorbiaceae) is a plant popularly used in Cameroon and in
      several parts of Africa for the treatment of various microbial diseases like
      diarrhea and skin infections. The present study was designed to evaluate the
      phytochemical composition, antimicrobial and radical-scavenging activities of A.
      manniana methanol leaf extract and its fractions. The methanol extract was
      partitioned into hexane, ethyl acetate and residual fractions and phytochemical
      analysis was conducted using standard methods. The broth microdilution method was
      used to evaluate the antimicrobial activity against nine bacterial species and
      four dermatophyte species. The free radical scavenging activities of the methanol
      extract and its fractions were evaluated using the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) assay. The results obtained showed that A. manniana contains alkaloids,
      tannins, anthocyanins, flavonoids, phenols and steroids. The methanol extract as
      well as the hexane, ethyl acetate and residual fractions exhibited both
      antibacterial and antidermatophytic activities that varied between the microbial
      species (MIC = 0.12 - 2.04 mg/mL). These tested samples also showed high radical
      scavenging activities (RaS50 = 3.34 - 4.80 MUg/mL) when compared with vitamin C
      used as reference antioxidant (RaS50 = 1.74 MUg/mL). These findings provide
      evidence that the studied plant possesses antimicrobial and antioxidant
      properties and may act as potential antioxidant for biological systems
      susceptible to free radical-mediated reactions. 

PMID- 24130963
TI  - Outcomes of patients with rodenticide poisoning at a far east poison center.
AB  - BACKGROUND: Rodenticide poisoning remains a major public health problem in Asian
      countries. Nevertheless, very few data are available in world literature
      regarding the outcomes of these patients. Therefore, the purpose of this study
      was to investigate the clinical outcomes of rodenticide poisonings in our
      hospital and to compare these data with published reports from other
      international poison centers. FINDINGS: We retrospectively examined the records
      of 20 patients with rodenticide poisoning (8 brodifacoum, 12 bromadiolone) who
      were referred to Chang Gung Memorial Hospital between 2000 and 2011. It was found
      that most of the rodenticide patients were middle-aged adults. Both genders were
      equally affected and many patients had a past history of major depressive
      disorder or schizophrenia. Nevertheless, patients with bromadiolone were referred
      significantly sooner than patients with brodifacoum poisoning (0.1 +/- 0.1 versus
      5.5 +/- 10.5, P < 0.001). Furthermore, it was found that patients with
      brodifacoum suffered higher incidences of ecchymosis (50.0% versus 0%, P = 0.006)
      and hematuria (50.0% versus 0%, P = 0.006) than patients with bromadiolone
      poisoning. Laboratory analysis also demonstrated a poorer hemostatic profile of
      patients with brodifacoum [prothrombin time (PT), international normalized ratio
      (INR), 4.3 +/- 4.8 versus 1.0 +/- 0.1, P = 0.032; PT prolongation, 50.0% versus
      0%, P = 0.006; activated partial thromboplastin time (aPTT) prolongation, 50.0%
      versus 0%, P = 0.006] than patients with bromadiolone poisoning. At the end of
      analysis, no patient died of the poisoning. CONCLUSION: The favorable outcome
      (zero mortality rate) is comparable to the published reports from other
      international poison centers. Further studies are warranted.

PMID- 24130965
TI  - Loss of Cdx2 Expression in Primary Tumors and Lymph Node Metastases is Specific
      for Mismatch Repair-Deficiency in Colorectal Cancer.
AB  - BACKGROUND: Approximately 20% of all colorectal cancers are hypothesized to arise
      from the "serrated pathway" characterized by mutation in BRAF, high-level CpG
      Island Methylator Phenotype, and microsatellite instability/mismatch repair (MMR)
      deficiency. MMR-deficient cancers show frequent losses of Cdx2, a homeodomain
      transcription factor. Here, we determine the predictive value of Cdx2 expression
      for MMR-deficiency and investigate changes in expression between primary cancers
      and matched lymph node metastases. METHODS: Immunohistochemistry for Cdx2, Mlh1,
      Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients
      with primary colorectal cancer and 59 cases of matched lymph node metastases.
      Receiver operating characteristic curve analysis and Area under the Curve (AUC)
      were investigated; association of Cdx2 with clinicopathological features and
      patient survival was carried out. RESULTS: Loss of Cdx2 expression was associated
      with higher tumor grade (p = 0.0002), advanced pT (p = 0.0166), and perineural
      invasion (p = 0.0228). Cdx2 loss was an unfavorable prognostic factor in
      univariate (p = 0.0145) and multivariate [p = 0.0427; HR (95% CI): 0.58 (0.34
      0.98)] analysis. The accuracy (AUC) for discriminating MMR-proficient and -
      deficient cancers was 87% [OR (95% CI): 0.96 (0.95-0.98); p < 0.0001].
      Specificity and negative predictive value for MMR-deficiency was 99.1 and 96.3%.
      One hundred and seventy-four patients had MMR-proficient cancers, of which 60
      (34.5%) showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency
      (p < 0.0001). There was no difference in expression between primary tumors and
      matched metastases. CONCLUSION: Loss of Cdx2 is a sensitive and specific
      predictor of MMR-deficiency, but is not limited to these tumors, suggesting that
      events "upstream" of the development of microsatellite instability may impact
      Cdx2 expression.

PMID- 24130964
TI  - Targeting the epigenome in lung cancer: expanding approaches to epigenetic
      therapy.
AB  - Epigenetic aberrations offer dynamic and reversible targets for cancer therapy;
      increasingly, alteration via overexpression, mutation, or rearrangement is found
      in genes that control the epigenome. Such alterations suggest a fundamental role
      in carcinogenesis. Here, we consider three epigenetic mechanisms: DNA
      methylation, histone tail modification and non-coding, microRNA regulation.
      Evidence for each of these in lung cancer origin or progression has been
      gathered, along with evidence that epigenetic alterations might be useful in
      early detection. DNA hypermethylation of tumor suppressor promoters has been
      observed, along with global hypomethylation and hypoacetylation, suggesting an
      important role for tumor suppressor gene silencing. These features have been
      linked as prognostic markers with poor outcome in lung cancer. Several lines of
      evidence have also suggested a role for miRNA in carcinogenesis and in outcome.
      Cigarette smoke downregulates miR-487b, which targets both RAS and MYC; RAS is
      also a target of miR-let-7, again downregulated in lung cancer. Together the
      evidence implicates epigenetic aberration in lung cancer and suggests that
      targeting these aberrations should be carefully explored. To date, DNA
      methyltransferase and histone deacetylase inhibitors have had minimal clinical
      activity. Explanations include the possibility that the agents are not
      sufficiently potent to invoke epigenetic reversion to a more normal state; that
      insufficient time elapses in most clinical trials to observe true epigenetic
      reversion; and that doses often used may provoke off-target effects such as DNA
      damage that prevent epigenetic reversion. Combinations of epigenetic therapies
      may address those problems. When epigenetic agents are used in combination with
      chemotherapy or targeted therapy it is hoped that downstream biological effects
      will provoke synergistic cytotoxicity. This review evaluates the challenges of
      exploiting the epigenome in the treatment of lung cancer. 

PMID- 24130967
TI  - Globus hystericus.
AB  - Globus hystericus (GH) is a subjective feeling of a lump or foreign body in the
      throat thought to involve psychogenic factors, a form of somatisation disorder.
      The more modern terms, globus sensation or globus pharyngeus, reflect recognition
      of one or more possible contributing anatomico-physiological factors, such as
      gastro-oesophageal reflux disease (GORD) or pharyngeal inflammation. 

PMID- 24130966
TI  - Mycobacterium tuberculosis and the host cell inflammasome: a complex
      relationship.
AB  - The production of IL-1beta during the infection with Mycobacterium tuberculosis
      (Mtb) is important for successful host immune defense. In macrophages and
      dendritic cells the host cell inflammasome is crucial for generation of secreted
      IL-1beta in response to Mtb infections. In these cell types Mtb infection only
      activates the NLRP3-inflammasome. New reports demonstrate that nitric oxide has
      an important function in the negative regulation of the NLRP3-inflammasome to
      reduce tissue damage during Mtb infections. The type I interferon, IFN-beta, is
      induced after Mtb infections and can also suppress NLRP3-inflammasome activation.
      In contrast, IFN-beta increases activity of the AIM2-inflammasome after infection
      with intracellular pathogens such as Francisella tularensis and Listeria
      monocytogenes. Recent results demonstrate that non-tuberculous mycobacteria but
      not virulent Mtb induce the AIM2-inflammasome in an IFN-beta dependent matter.
      Indeed, Mtb inhibits AIM2-inflammasome activation via its ESX-1 secretion system.
      This novel immune evasion mechanism may help Mtb to allow the induction of low
      levels of IFN-beta to suppress the NLRP3-inflammasome without activating the AIM2
      inflammasome. 

PMID- 24130968
TI  - Multiple myeloma: from diagnosis to treatment.
AB  - BACKGROUND: Multiple myeloma is characterised by the proliferation of malignant
      plasma cells within the bone marrow, which produce an abnormal monoclonal
      paraprotein and evidence of end organ damage. OBJECTIVE: Multiple myeloma can
      pose a diagnostic challenge and this article highlights issues in diagnosis and
      provides an overview of management. DISCUSSION: Multiple myeloma can present with
      a wide constellation of symptoms including hypercalcaemia, anaemia, renal
      impairment and/or bony pain. A combination of these symptoms, particularly if
      unexpected or unexplained, should prompt diagnostic evaluation for myeloma. Work
      up of plasma cell disorders involves establishing the presence of a monoclonal
      paraprotein, baseline bloods and radiological investigations. Haematology
      referral is required for bone marrow biopsy and ongoing management. Newer
      treatments such as the immunomodulators thalidomide or lenalidomide, or the
      proteasome inhibitor bortezomib, administered in combination with steroids and
      occasionally cytotoxic agents have improved outcomes in patients with myeloma.
      Autologous stem cell transplant is offered to younger patients with few
      comorbidities. Some patients are offered maintenance therapy with thalidomide or
      lenalidomide.

PMID- 24130969
TI  - Fibromylagia.
AB  - BACKGROUND: Fibromyalgia is a common and debilitating condition. The cardinal
      feature of fibromyalgia is musculoskeletal pain, usually accompanied by other
      problems, such as fatigue, sleep disturbance and cognitive difficulties.
      Fibromyalgia commonly coexists with other chronic illnesses and can result in
      poorer outcomes if untreated. OBJECTIVE: The objective of this review is to
      discuss when fibromyalgia should be considered as a diagnosis, how it is
      diagnosed, the current understanding of the pathophysiology of fibromyalgia and
      the management strategies available. DISCUSSION: The features of fibromyalgia are
      similar to those of many other chronic illnesses, sometimes resulting in
      diagnostic confusion. Fibromyalgia can co-exist with other disorders and it is
      important to consider the possibility of fibromyalgia contributing to symptoms in
      any chronically ill patient.

PMID- 24130970
TI  - Systemic lupus erythmatosus - When to consider and management options.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised
      by multi-system manifestations. It is regarded as the prototypal connective
      tissue disease, where the key pathogenesis relates to a dysfunctional immune
      system that results in over-production of various autoantibodies. Most of its
      pathology is mediated by either direct or indirect effects of these
      autoantibodies, as well as other components of the innate and adaptive immune
      systems. 

PMID- 24130971
TI  - Dual antiplatelet therapy -- management in general practice.
AB  - BACKGROUND: Prasugrel and ticagrelor are two new antiplatelet agents being used
      in the management of acute coronary syndromes. The number of patients in the
      community managed on these medications is growing, and thus, it is essential that
      general practitioners have a good understanding of these agents and their
      evidence-based applications. OBJECTIVE: The pharmacokinetic and pharmacodynamic
      properties of common and new antiplatelet agents will be reviewed, along with the
      evidence supporting their use. Safety and side effect profiles will be discussed,
      and some common general practice case scenarios presented. DISCUSSION: Aspirin is
      still the mainstay of therapy in patients with acute coronary syndromes. The
      addition of clopidogrel, prasugrel or ticagrelor can reduce morbidity and
      mortality in selected patients. Patient factors including bleeding risk, renal
      function and time since coronary stent insertion must be reviewed before these
      agents are initiated and before making any changes to the medication regimen.

PMID- 24130972
TI  - SGLT2 inhibition with dapagliflozin -- a novel approach for the management of
      type 2 diabetes.
AB  - BACKGROUND: Because of the progressive nature of the disease, most patients with
      type 2 diabetes mellitus eventually require multiple treatments to achieve
      glycaemic targets. The majority of available therapies are insulin dependent,
      aiming to decrease insulin resistance and increase insulin secretion. Sodium
      glucose co-transporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents,
      limit renal glucose reabsorption promoting urinary excretion of glucose, thereby
      reducing plasma glucose. OBJECTIVE: This article explores the mechanism of action
      and clinical data surrounding SGLT2 inhibitors, with a particular focus on
      dapagli-flozin. CONCLUSION: Clinical trials have shown dapagliflozin to be
      effective in reducing glycosylated haemoglobin, weight and fasting plasma
      glucose, either as monotherapy or as add-on therapy to metformin, sulphonylurea
      and insulin. Other SGLT2 inhibitors are currently under investigation.

PMID- 24130973
TI  - Managing opioid dependence in pregnancy -- a general practice perspective.
AB  - BACKGROUND: Managing opioid dependence in pregnant women is a complex and
      potentially challenging task. Drug-dependent women may be difficult to engage in
      antenatal care and opioid substitution requires careful dose titration.
      Pregnancy, however, can be an opportune time to effect behaviour change, and
      supporting an opioid-dependent woman through pregnancy can be a rewarding
      clinical experience. OBJECTIVE: This article provides an overview of treatment
      principles for managing opioid dependence in pregnancy, and reviews current
      treatment guidelines for use of opioid-substitution therapy in pregnant women.
      DISCUSSION: The management of opioid dependence during pregnancy requires
      holistic and comprehensive assessment and referral to specialist services is
      often appropriate. Specific issues that may need to be addressed include decision
      making regarding the choice of opioid-substitution therapy and the potential for
      neonatal abstinence syndrome in the newborn. General practitioners are often well
      placed to support and coordinate care of their opioid-dependent pregnant
      patients.

PMID- 24130974
TI  - Antinuclear antibody test.
AB  - The antinuclear antibody (ANA) test is widely used as a serological marker of
      autoimmune disease. Antinuclear antibodies are immunoglobulins or antibodies that
      bind to one or more antigens expressed within the nucleus of human cells. Used
      selectively, the ANA test can be a useful laboratory tool to help confirm or
      exclude the diagnosis of systemic rheumatic disease. However, the relatively high
      prevalence of ANAs in other inflammatory conditions, as well as healthy
      individuals, can make a positive result difficult to interpret. 

PMID- 24130975
TI  - Skin rash on the upper limbs -- case studies.

PMID- 24130976
TI  - Taping for knee osteoarthritis.
AB  - Taping can be used to reduce pain in knee osteoarthritis. There are different
      methods of taping, but the common effect is to exert a medially directed force on
      the patella to increase the patellofemoral contact area, thereby decreasing joint
      stress and reducing pain. Taping can be performed by a physiotherapist, but self
      taping can be taught, which enhances self management. Taping for knee
      osteoarthritis has National Health and Medical Research Council (NHMRC) Level I
      evidence of efficacy for pain relief and is associated with negligible adverse
      effects that generally include minor skin irritation. 

PMID- 24130977
TI  - Practice nurses and sexual health care -- enhancing team care within general
      practice.
AB  - BACKGROUND: Collaboration between general practitioners (GPs) and practice nurses
      (PNs) can enhance health care delivery. However, despite evidenced shortfalls in
      general practice-based sexual health care, the PN role in sexual health appears
      underdeveloped. Evaluation of New South Wales Sexually Transmissible Infections
      Programs Unit GP Project provided an opportunity to canvass views of GPs and PNs
      regarding PNs and sexual health care. METHODS: A purposively sampled group of 10
      PNs and nine GPs were interviewed. Interviews were transcribed and analysed
      thematically. RESULTS: The extent and nature of PN-GP teamwork in sexual health
      care was variable, influenced largely by GP recognition and support of the PN
      role in sexual health care. Other important factors were personal PN interest and
      supportive practice systems. DISCUSSION: The role played by PNs and a team
      approach to sexual health care in Australian general practice is underdeveloped.
      Increased recognition and support of PN roles in sexual health is needed,
      including supportive practice systems that facilitate team care.

PMID- 24130978
TI  - Surviving an epidemic -- Australian GPs on caring for people with HIV and AIDS in
      the early years.
AB  - BACKGROUND: Although general practitioners (GPs) play a central role in
      responding to human immunodeficiency virus (HIV) in Australia, the social history
      of their contribution in the early years has remained largely untold. METHODS: In
      depth interviews were conducted with 21 GPs who provided HIV care between 1982
      and 1996. De-identified transcripts were broadly coded in NVivo, then analysed
      for themes regarding GP experiences during the early years. RESULTS: Participants
      recalled a time of death, fear and prejudice, with large numbers of patients
      diagnosed with and dying from a highly stigmatised disease. An enduring emotional
      legacy resulted, with GPs developing survival strategies such as better managing
      relationships with patients, seeking mental health support and reducing working
      hours. DISCUSSION: These GPs represent the first generation of GPs in Australia
      caring for people with HIV. Understanding their experiences can inform and
      inspire the next generation, who inherit a much brighter future for HIV care.

PMID- 24130979
TI  - Asthma control in general practice -- GP and patient perspectives compared.
AB  - BACKGROUND: How general practitioners (GPs) and patients perceive asthma control,
      and concordance between these perceptions, may influence asthma management and
      medication adherence. The aims of this study were to determine asthma prevalence
      in adult patients, measure patient asthma control and the correlation between GP
      and patient perceptions of asthma control or impact. METHODS: A Supplementary
      Analysis of Nominated Data (SAND) sub-study of the Bettering the Evaluation and
      Care of Health (BEACH) program surveyed 2563 patients from 103 GPs. Asthma
      control was measured using the Asthma Control Questionnaire 5-item version (ACQ
      5), and medication adherence by patient self-report. Survey procedures in SAS
      software and Pearson's correlation statistics were used. RESULTS: Asthma
      prevalence was 12.7% (95% confidence interval: 10.9-14.5), with good correlation
      between GP and patient perceptions of asthma control/impact, and with raw ACQ-5
      scores. Grouped ACQ-5 scores showed higher levels of uncontrolled asthma.
      Medication adherence was sub-optimal. DISCUSSION: The ACQ-5 questions are useful
      for assessing asthma control, for prompting medication reviews, and for
      reinforcing benefits of medication compliance to improve long-term asthma
      control.

PMID- 24130980
TI  - A is for aphorism -- 'give me a child until they are seven and I will show you
      the man'.
AB  - This aphorism is true for some, but not most. Child development is about both
      continuity and change. Experiences in early childhood shape cognitions and new
      experiences are integrated into familiar models of relationships. For example,
      children who have experienced rejection from parents will often assume rejection
      from others, not initiate positive contacts, isolate themselves, and consequently
      experience rejection from peers. But they may also experience a caring and
      supportive teacher who assists them in making lifelong friends who change their
      perceptions and expectations. So, early experience matters and early family life
      plays an important role in child development outcomes. 

PMID- 24130981
TI  - Duty of care or a matter of conduct -- can a doctor refuse a person in need of
      urgent medical attention?
AB  - BACKGROUND: Medical practitioners may have their particular skills called upon
      outside a direct professional context. The responsibilities of medical
      practitioners outside their defined scope of clinical practice may not be clear
      to all clinicians. OBJECTIVE: To consider the possible legal consequences of a
      doctor refusing to assist a person in need of urgent medical attention both in
      terms of medical negligence and professional misconduct. DISCUSSION: Where an
      established clinical relationship does not exist, and a doctor does not wish to
      render aid, three particular scenarios may arise. A doctor may actively deny
      being a doctor, passively avoid identifying themselves as a doctor or acknowledge
      being a doctor, but refuse to render assistance. Aside from any ethical issues,
      how a doctor chooses to act and represent themselves may lead to different legal
      ramifications. There exists significant variation in state provisions relating to
      legal obligations to render aid, which may benefit from review and revision at a
      national level.

PMID- 24130982
TI  - Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic
      resistance of erythrocytes.
AB  - We studied the effects of the anorexigenic peptide obestatin on the coagulation
      system and blood rheology (by the parameters of platelet aggregation and osmotic
      resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro
      platelet aggregation in the entire dose range and reduced osmotic resistance of
      erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg
      had no effect on this parameter). Similar to the results of in vitro experiments,
      intranasal, intraperitoneal, and subcutaneous administration of obestatin in a
      dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the
      osmotic resistance of erythrocytes. 

PMID- 24130983
TI  - Effect of pegylated hyaluronate-endo-beta-N-acetylhexosaminidase on humoral
      mechanisms regulating the functions of progenitor cells during chronic hepatitis.
AB  - We studied the effect of hyaluronate-endo-beta-N-acetylhexosaminidase on the
      secretory function of the liver and bone marrow microenvironment cells in chronic
      hepatitis. Enhanced production of substances stimulating parenchymal tissue
      specific precursors and stem cell homing factors by liver cells was revealed. At
      the same time, production of SDF-1 and other chemoattractants and adhesion
      factors of progenitor cells by bone marrow elements was reduced. 

PMID- 24130984
TI  - Changes in contractile activity of rabbit colon under stress conditions and
      during post-stress period before and after blockade of muscarinic and nicotinic
      cholinergic receptors.
AB  - Psychogenic stress in rabbits induced by fixation of the animal to a frame was
      accompanied by an increase in contractile activity of the initial portion of the
      distal colon, which was abolished by blockade of muscarinic and nicotinic
      cholinergic receptors. Increased contractile activity of the colon was due to
      centrogenic stimulation of preganglionic neurons of the parasympathetic nervous
      system followed by the involvement of the effector cholinergic neurons of the
      enteric nervous system into excitation. 

PMID- 24130985
TI  - Experimental substantiation of the efficiency of antioxidant therapy for post
      traumatic arthritis.
AB  - Experimental post-traumatic arthritis was accompanied by overexpression of pro
      inflammatory cytokines and imbalance in the collagen metabolism. Intraarticular
      injection of mexidol prevented free-radical degradation of collagen structures,
      contributed to activation of collagen synthesis and cartilage repair, and reduced
      the severity of inflammatory changes in the joint and the degree of secondary
      alteration of tissue structures. 

PMID- 24130986
TI  - Effect of prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)
      cyanopyrrolidine on the course of experimental depressive syndrome in rats.
AB  - The effects of noncompetitive prolyl endopeptidase inhibitor benzyloxycarbonyl
      methionyl-2(S)-cyanopyrrolidine were studied in rats with the experimental
      dopamine deficiency-dependent depressive syndrome induced by systemic injections
      of a pre-neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin for 14 days. The
      inhibitor (3.0 mg/kg, i.p., 30 min before pre-neurotoxin injection on days 8-14)
      alleviated depression symptoms and promoted normalization of behavioral activity
      after drug withdrawal. The obtained data reflected therapeutic antidepressant
      properties of inhibitor for prolyl endopeptidase benzyloxycarbonyl-methionyl-2(S)
      cyanopyrrolidine. 

PMID- 24130987
TI  - Tonic pain response during inflammation and stress-induced corticosterone
      variations in prenatally stressed infant rats: effects of maternal buspirone
      injected during pregnancy.
AB  - We studied the effects of injections of 5-HT1A-agonist buspirone to pregnant rats
      before stress exposure on corticosterone level in the dynamics of stress response
      to inflammatory-induced pain in 7-day-old offspring. During the period of the
      hypothalamic-pituitary-adrenal system hyporeactivity, the pain response in the
      formalin test was associated with stress-related corticosterone variations.
      Maternal buspirone normalized the pain reaction in prenatally stressed rats
      during all periods of the formalin test and modified the dynamics of the
      corticosterone response. In 1 day after the formalin test, the basal level of
      this hormone in blood plasma remained increased. Maternal buspirone increased the
      resistance of the nociceptive and stress-systems to inflammatory-induced pain
      response in prenatally stressed rats. 

PMID- 24130988
TI  - Optimization of choline administration regimen for correction of cognitive
      functions in rats after brain injury.
AB  - Choline diet promotes improvement of the brain cognitive functions in rats with
      moderate-to-severe traumatic brain injury. In previous studies, the rats received
      choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior
      to and 2 weeks after experimental brain injury. To the end of the experiments (in
      4 weeks), the post-traumatic disturbances in the cognitive functions were
      observed in both groups, although they were less pronounced than in the rats kept
      on the choline-supplemented diet. Based on original mathematical model, this
      paper proposes a method to calculate the most efficient use of choline to correct
      the brain cognitive functions. In addition to evaluating the cognitive functions,
      the study assessed expression of alpha7 nicotinic acetylcholine receptors, the
      amount of consumed food and water, and the dynamics of body weight.

PMID- 24130989
TI  - Anxiolytic activity of dipeptide GB-115 after oral administration.
AB  - The anxiolytic effects of GB-115, a retroanalogue of cholecystokinin-4,
      administered orally to outbred and inbred animals with different level of
      emotionality, were studied in the open field test and elevated plus-maze test.
      The anxiolytic effect of talanax was observed in outbred mice (0.1-0.5 mg/kg) and
      in inbred BALB/c mice (0.1 and 5.0 mg/kg) in the open field test. GB-115
      increased the time of entries into open arms in outbred rats (0.5-0.7 mg/kg) and
      in BALB/c mice (0.1 mg/kg). These data confirmed the dependence of GB-115 effect
      on the phenotype of emotional stress response and demonstrated a shift of
      anxiolytic doses of the preparation from 0.006-0.100 mg/kg in intraperitoneal
      administration to 0.1-5.0 mg/kg in oral treatment. 

PMID- 24130990
TI  - Antidepressant, psychostimulant, and nootropic effects of major and trace element
      composition.
AB  - The antidepressant, psychostimulant, and nootropic effects of a composition of
      major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc
      sulfate were studied on the models of behavioural despair (Porsolt test) and
      conditioned passive avoidance test. The preparation was found to shorten the
      immobilization time in the Porsolt test and promote retention of the conditioned
      passive avoidance. The most pronounced psychostimulant effect of the substance
      was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant
      effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the
      preparation was found at a dose of 93.6 mg/kg. 

PMID- 24130991
TI  - Mechanisms of stimulating effect of glycyram and D-glucuronic acid on
      granulocytopoiesis suppression by 5-fluorouracil.
AB  - We compared hemostimulating activity of glycyram and a preparation of D
      glucuronic acid on the model of granulocytic hemopoiesis suppressed by 5
      fluorouracil. Different mechanisms were shown to underlie activation of
      hemopoiesis by the above preparations: D-glucuronic acid directly affects
      hemopoietic cells, while glycyram modulates local mechanisms regulating
      hemopoiesis. 

PMID- 24130992
TI  - Experimental substantiation for the use of mexidol and 3-hydroxypyridine fumarate
      in chronic myocardial injury.
AB  - We studied the cardioprotective properties of mexidol and 3-hydroxypyridine
      fumarate in rat model of chronic myocardial injury. We found that 3
      hydroxypyridine fumarate (25 mg/kg) produced more pronounced antioxidant and
      cardioprotective effects than mexidol (25 mg/kg). 

PMID- 24130993
TI  - Protective effect of fenspiride on the bronchi in rats with chronic obstructive
      pulmonary disease.
AB  - We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on
      contractive activity of bronchial smooth muscles on the model of chronic
      obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen
      dioxide. The administration of fenspiride during the acute stage of the disease
      (day 15) abolished the constricting effect of the pollutant on the bronchial
      smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was
      mediated by its interaction with nerve endings of bronchial capsaicin-sensitive
      nerve C-fibers. The interaction of drug with receptors of C-fibers prevented
      neurogenic inflammation, which was confirmed by the absence of structural changes
      in the lungs typical of this pathology. The broncholytic effect of fenspiride in
      a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its
      direct relaxing action on smooth muscle cells. The observed anti-inflammatory and
      bronchodilatation effect of fenspiride in very low doses can be used for
      prevention of chronic obstructive pulmonary disease in risk-group patients
      contacting with aggressive environmental factors. 

PMID- 24130994
TI  - Use of inclusion complex of cyclodextrin with ambenonium to improve the treatment
      of anticholinesterase poisoning.
AB  - The complex of ambenonium with methyl-beta-cyclodextrin injected intramuscularly
      to rats caused more pronounced inhibition of acetylcholinesterase in erythrocyte
      and brain than free drug. The use of this complex as part of combined therapy
      significantly reduces mortality in animals during experimental anticholinesterase
      poisoning in comparison with the controls. 

PMID- 24130995
TI  - Immunorehabilitating effect of ultrahigh frequency electromagnetic fields in
      immunocompromised animals.
AB  - We observed immunorehabilitation effects of ultrahigh frequency electromagnetic
      fields (microwaves) in immunocompromised animals. It was shown that microwave
      irradiation of the thyroid gland area could abolish actinomycin D- and colchicine
      induced immunosuppression and did not affect immunosuppression caused by 5
      fluorouracil. These findings suggest that changes in the hormonal profile of the
      organism during microwave exposure can stimulate the processes of transcription
      and mitotic activity of lymphoid cells. 

PMID- 24130996
TI  - Dioxidine-induced changes in genome-wide DNA methylation in a culture of
      peripheral blood lymphocytes.
AB  - We studied the effect of dioxidine on genome-wide methylation in short-term
      cultures of peripheral blood lymphocytes derived from healthy donors. Methylation
      was evaluated in lymphocytes before culturing, after 25 h in culture, and 1 h
      after addition of dioxidine in two concentrations (0.1 and 0.01 mg/ml). The total
      time in culture was 25 h. The level of methylation was assessed using methyl
      sensitive single-cell gel electrophoresis ("comet assay") with additional
      restriction with HpaII amd MspI. Significant individual differences were found in
      the levels of methylation in both native cells and in cells treated with
      dioxidine in both concentrations. Mean group indicators of methylation did not
      differ before culturing and after 25 h in culture (45.28 and 44.80%,
      respectively). The mean group rate of methylation increased to 46.14% (p<0.001)
      after dioxidine treatment in a concentration of 0.01 mg/ml. Dioxidine in 0.1
      mg/ml reduced the level of methylation (mean group rate 42.31%; p<0.001). 

PMID- 24130997
TI  - Cytotoxic effect of doxorubicin on human multiple myeloma cells in vitro.
AB  - Cytotoxic effect of doxorubicin in human multiple myeloma cell cultures RPMI
      1640, RPMI 8226, and IM-9 was studied. The obtained data were compared with mRNA
      expression of MDR1, MRP1, BCRP, LRP genes responsible for the development of
      multiple drug resistance. IM-9 cells that differed from the other two cultures by
      the expression of surface differentiation markers and by mRNA expression of MDR1,
      BCRP, and LRP were most sensitive to doxorubicin. All cells expressed mRNA for
      only A-isoform of insulin receptor (IRA), while B-isoform (IRB) was not
      expressed. Insulin in a concentration of 5 MUg/ml had no effect on the cytotoxic
      effect of doxorubicin in the studied cells. 

PMID- 24130998
TI  - Changes in the state of hemoglobin in patients with coronary heart disease and
      patients with circulatory failure.
AB  - Morphology of erythrocytes and conformation of hemoglobin-derived hematoporphyrin
      were studied in patients with coronary heart disease (CHD) and patients with
      circulatory failure using laser interference microscopy and Raman spectroscopy.
      Correlation was revealed (r=0.81) between hemoglobin oxygen saturation and
      oxyhemoglobin fraction in erythrocytes evaluated by Raman spectroscopy. Patients
      with CHD and patients with circulatory failure showed reduced oxygen-releasing
      capacity of hemoglobin and hemoglobin content and increased oxygen-binding
      capacity of hemoglobin, and hemoglobin affinity for oxygen. Significant
      differences from the control were observed only in patients with circulatory
      failure. It was found that hemoglobin content, hematocrit, and the shape of
      erythrocytes during CHD and circulatory failure did not differ from the control,
      whereas the area of erythrocytes was increased. 

PMID- 24130999
TI  - Identification of silver nanoparticles in the small intestinal mucosa, liver, and
      spleen of rats by transmission electron microscopy.
AB  - The effects of water-dispersed Ag nanoparticles on the small intestinal mucosa,
      liver, and spleen of rats were studied by transmission electron microscopy. Acute
      experiments demonstrated penetration of Ag nanoparticles injected into the
      isolated intestinal loop into the intestinal mucosa, liver, and splenic tissues.
      Ultrastructural changes (lobed nucleus, megamitochondria) were found in the
      studied organs. These data indicated that injection of water-dispersed Ag
      nanoparticles into the gastrointestinal tract was followed by their penetration
      through the epithelium of the small intestinal mucosa into other organs, e.g.
      into the liver and spleen. This fact is essential for evaluation of potential
      risks of the nanoparticle effects on human health and environment. 

PMID- 24131000
TI  - Involvement of BDNF and NGF in the mechanism of neuroprotective effect of human
      recombinant erythropoietin nanoforms.
AB  - Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate
      nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg
      exhibited a neuroprotective effect in experimental intracerebral posttraumatic
      hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant
      erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based
      nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse
      transcription PCR products showed that human recombinant erythropoietin adsorbed
      on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the
      expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and
      hippocampus. 

PMID- 24131001
TI  - Study of cardioprotective effects of necroptosis inhibitors on isolated rat heart
      subjected to global ischemia-reperfusion.
AB  - The cardioprotective effects of necroptosis inhibitors necrostatin-1 and
      necrostatin-5 were studied on the isolated heart model in rats. Intraperitoneal
      injection of necrostatin-1 (1.65 mg/kg) or necrostatin-5 (2.46 mg/kg) 60 min
      before reperfusion of the isolated heart reduced the infarction zone caused by 30
      min global ischemia and 120-min reperfusion. Intracoronary injection of
      necrostatin-1 (44.5 MUmol/liter) caused an increase of left-ventricular systolic
      pressure, that is produced a positive inotropic effect, but did not reduce the
      infarction zone. 

PMID- 24131002
TI  - Pathomorphological analysis of the pancreaticoduodenal organs in experimental
      pancreonecrosis induced by trypsin injection.
AB  - Acute experimental pancreatitis induced by injection of trypsin into the
      pancreatic tissue exhibited characteristics of fulminant hemorrhagic
      pancreonecrosis (intense exudation of interlobular stroma, massive plasmo- and
      hemorrhages, foci of acinar cell autolysis involving by the end of day 1 an
      appreciable portion of the organ with formation of fields of necrosis and
      hemorrhagic imbibition of the glandular parenchyma, virtually completely without
      demarcation cellular reaction). Marked microcirculatory disorders and
      degenerative and necrobiotic changes in the duodenal mucosa and liver reflected
      the polyorgan nature of the pathological process. This model of hemorrhagic
      pancreonecrosis corresponded to the most severe forms of this conditions observed
      clinically. 

PMID- 24131003
TI  - Adaptation capacity of microcirculatory bed of the skin under conditions of high
      frequency rate fractionated automated tibial elongation.
AB  - The status of the microcirculatory bed in the skin in the bone regenerate
      projection was studied under conditions of fractionated automated tibial
      elongation by transosteal distraction osteosynthesis at a rate of 3 mm/day in
      adult mongrel dogs. Histological and physiological data indicated that the
      distraction period was associated with changes in the functional components of
      the skin microcirculatory bed. Active neovasculogenesis and formation of
      additional arteriovenular anastomoses provided sufficient oxygenation of tissues
      and maintained venous outflow. This led to rapid recovery of the functional
      potentialities of skin microvessels as early as 1 month after the end of forced
      fixation. 

PMID- 24131004
TI  - Ultrastructural characteristics of molecular release of secretory products from
      thyroid mast cells induced by lipopolysaccharide.
AB  - Ultrastructural characteristics of molecular release of secretory products from
      thyroid mast cells during different periods after LPS injection were studied in
      rats. The main morphological manifestation of this mechanism was progressing
      hydration of the hyaloplasm around secretory granules and dissolution and release
      of osmiophilic contents from the granules to the cytoplasm with the formation of
      a hydropic vacuole at the site of the granule. 

PMID- 24131005
TI  - Electrophysiological correlations of morphological restructuring in experimental
      local ischemia of different severity in the rat sensorimotor cortex.
AB  - Local cerebrovascular disorders were modeled by reversible photochemical clotting
      of hemispheric cortical vessels. Mild ischemia led to reversible edema in the
      surface layers of the cortex: cytotoxic edema of the neuropile, primarily of the
      distal dendrites. This status led to an increase in the lower delta rhythm
      frequency band power. After administration of systemic anesthetic, delta rhythm
      appeared sooner in the ischemic foci than in intact cortical areas. More severe
      ischemia led to the appearance of dark and pyknotic neurons and reduction of
      oscillation power in all EEG spectrum bands. Restructuring of primarily dendrites
      caused by local moderate ischemia of the surface cortical layers at the early
      stage of neurodegenerative processes stimulated the inhibitory recovery
      processes. 

PMID- 24131006
TI  - Age-associated changes in sympathetic neurons containing neurofilament 200 kDa
      during chemical deafferentation.
AB  - Neurofilament with a molecular weight of 200 kDa is detected in the rat
      sympathetic ganglia since birth. The percentage of neurons containing this
      neurofilament decreases during the first 20 days of life. Just solitary
      neurofilament-positive neurons are detected in rats at the age of 180 and 360
      days. Chemical deafferentation by capsaicin, used as a model of age-associated
      neuron degeneration, leads to a significant reduction of the level of
      neurofilament-200-imminopositive neurons in comparison with the control starting
      from day 10 of life. Presumably, part of the sympathetic ganglionic neurons are
      capsaicin-positive and their function is afferent. 

PMID- 24131007
TI  - Behavioral characteristics of ovariectomied Wistar rats trained in a maze. Effect
      of mental stress and castration for infradian rhythms.
AB  - Four psychotypes differing by cognitive activity and psychoemotional reactions
      were distinguished in a population of orchiectomied Wistar rats and in a
      population of intact animals on the model of a complex cognitive test combined
      with the free choice method. With similar parameters of cognitive activity, the
      psychotypes of castrated rats were inferior to those of intact animals by the
      number of psychoemotional reactions and levels of locomotor activity. Infradian
      rhythms of spontaneous locomotor activity with a 4-day period were detected in
      intact and castrated rats. These rhythms did not change under the effect of
      mental stress, associated with food-getting behavior training, and did not depend
      on testosterone level. 

PMID- 24131008
TI  - Immunolocation of cystationine beta-synthase in cerebral pontile nuclei in
      humans.
AB  - The immunolocation of cystationine beta-synthase in the motor, sensitive, and
      autonomic nuclei of the cerebral pons was studied on the material from 8 healthy
      men aged 18-44 years dead from traumas not involving the CNS. The motor nuclei
      contained numerous large intensely stained cells, while the sensitive and
      autonomic nuclei contained many small neurons with low levels of cystationine
      beta-synthase marker. However, cells with intense reaction were found among small
      neurons. They were located mainly at the nuclear periphery, between the nuclei or
      between the nuclei and conduction tracts. The content of immunopositive neurons
      in the studied nuclei varied from 2 to 14%. The level of these cells in motor
      nuclei was 3-4-fold higher than in sensitive and autonomic nuclei. 

PMID- 24131009
TI  - Contractile activity of living isolated neurons and its inhibition by
      cytochalasin B.
AB  - Contractile activity of damaged neuronal axons of Lymnaea stagnalis and Planorbis
      corneus vulgaris mollusks and the possibility of inhibiting their retraction by
      cytochalasin B were studied. In experimental series I (control), the neuronal
      axons contracted in Ringer's fluid in 90% cases. In series II and III
      (cytochalasin B in concentrations of 0.02 and 0.2 mM), the percentage of non
      contracting neurons was 50 and 70%, respectively. Presumably, the fiber
      retraction mechanism was involved in the formation of diastasis after nerve
      cutting and damage to conduction tracts. The nerve diastasis formed at the
      expense of not only elastic characteristics of the nerve sheath and glia, but
      also due to nerve fiber retraction. Experiments with cytochalasin B demonstrated
      that F-actin filaments were involved in the retraction of myelin-free nerve
      fibers. 

PMID- 24131010
TI  - Comparative characteristics of lipemia models induced by injections of Triton WR
      1339 and poloxamer 407 in mice.
AB  - Lipemia modeled by injections of Triton WR-1339 (500 mg/kg) and poloxamer 407
      (500 mg/kg) to mice were compared. LP fraction and subfraction compositions were
      compared by small-angle X-ray scattering on a diffractometer. Both compounds in
      the same dose caused a sharp increase in serum concentrations of total
      cholesterol (CH) and triglycerides (TG), the increases in response to poloxamer
      407 being more pronounced. The differences in the models consisted in the levels
      of atherogenic fractions: CH-VLDL (subfractions CH-VLDL1-2) and CH-LDL, which
      were higher under the effect of poloxamer 407. Similar increases were observed
      for atherogenic fractions: TG-VLDL (subfractions TG-VLDL1-2) and TG-LDL
      (subfractions TG-LDL1-3). A specific feature of the model induced by poloxamer
      407 was elevation of the concentrations of antiatherogenic CH-HDL and TG-HDL
      (subfractions CH-HDL2 and TG-HDL2). Both models exhibited high similarity, but
      changes in atherogenic fractions were more pronounced under the effect of
      poloxamer 407.

PMID- 24131011
TI  - Efficiency assessment of shock wave therapy in patients with pelvic pain
      employing harmonic analysis of penile bioimpedance.
AB  - In searching for novel objective methods to diagnosticate pelvic pain and assess
      efficiency of analgesic therapy, 37 male patients were examined prior to and
      after the course of extracorporeal shock wave therapy (5-10 sessions) with the
      waves directed to projections of prostate and/or crura and shaft of the penis.
      The repetition rate of mechanical pulses was 3-5 Hz. The range of energy pulse
      density was 0.09-0.45 mJ/mm(2). The overall number of pulses in a session was
      1500-3000 in any treated zone with total energy smaller than 60 J. The applicator
      was relocated every other series of 300-500 pulses. Effect of the shock wave
      therapy was assessed according to subjective symptomatic scales: International
      Prostate Symptom Score, International Index of Erectile Function, Quality of
      Life, and nociceptive Visual Analog Scale. The objective assessment of shock wave
      therapy was performed with harmonic analysis of penile bioimpedance variability,
      which quantitatively evaluated the low-frequency rhythmic and asynchronous
      activities at rest as well as the total pulsatile activity of the penis. The
      magnitude of spectrum components of bioimpedance variations was assessed with a
      novel parameter, the effective impedance. The spectral parameters were measured
      in 16 patients prior to and after the treatment course. The corresponding control
      values were measured in the group of healthy patients. Prior to the shock wave
      therapy course, all spectrum parameters of penile bioimpedance significantly
      differed from the control (p<0.05). After this course, low-frequency rhythmic and
      the total pulsatile activity decreased to normal, while asynchronous activity
      remained significantly different from the normal. The novel objective
      physiological criteria of pelvic pain diagnostics and efficiency of its treatment
      reflecting the regional features of circulation and neural activity corresponded
      to the clinical symptom scaling prior to and after the shock wave course, and on
      the whole, these criteria corroborated improvement of the patient state after
      this therapy. 

PMID- 24131013
TI  - Reversible hydrazide chemistry-based enrichment for O-GlcNAc-modified peptides
      and glycopeptides having non-reducing GlcNAc residues.
AB  - O-Linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translational
      modification (PTM) of proteins. Analysis of O-GlcNAc modification using mass
      spectrometry (MS) is often problematic because of the low stoichiometry of the
      modification. In this study, we developed a new method for enriching O-GlcNAc
      modified peptides using reversible hydrazide chemistry. O-GlcNAc-modified
      peptides were first labeled with N-azidoacetylgalactosamine (GalNAz) using
      gatactosyltransferase-T1 (Y289L) enzyme. The azide group on the GalNAz residue
      was then reacted with 3-ethynylbenzaldehyde via copper-catalyzed Huisgen 1,3
      cycloaddition "click reaction" to form an aromatic aldehyde group of
      glycopeptides. Aromatic aldehyde-derivatized glycopeptides were enriched by
      reversible hydrazone formation with hydrazide resin. Reaction conditions for each
      step, especially for the click reaction, were optimized to achieve complete
      reaction without significant side reactions. This method was validated using a
      tryptic digest of bovine alpha-crystallin, which is an O-GlcNAc-modified
      glycoprotein. The developed method was also applied to structure-specific
      enrichment of N-linked glycopeptides having non-reducing terminal GlcNAc
      residues. All materials and chemicals required for this method are commercially
      available and there is no need to prepare any special reagents, facilitating the
      introduction of this method in any laboratory. 

PMID- 24131014
TI  - Terminal protection of small-molecule-linked DNA for sensitive fluorescence
      detection of protein binding based on nucleic acid amplification.
AB  - A novel fluorescence biosensing strategy based on terminal protection triggered
      nucleic acid amplification reaction upon target binding was developed for the
      sensitive detection of small molecule-protein interactions. This method relies on
      the specific interactions between target proteins and their small molecule-linked
      DNA to produce a ligation probe. Introduction of a target protein into the assay
      system protected the small molecule-linked DNA from Exonuclease I (Exo I)
      mediated digestion and served as the circular template to trigger rolling circle
      amplification (RCA). The RCA product containing thousands of repeated sequences
      could hybridize with the TaqMan probes (reporter probes) and were then detected
      by Exonuclease III (Exo III)-aided recycling amplification reaction, generating
      remarkable fluorescence signals. This developed strategy transduced small
      molecule-protein interactions into DNA amplification and detection techniques.
      Due to the primary RCA followed by the secondary Exo III-aided recycling
      amplification, the developed method was demonstrated to have very high
      sensitivity for the detection of a tumor biomarker of folate receptor with a
      limit of detection of 0.8 pM. The novel strategy holds great promise for the
      study of small molecule-protein interactions with desirable specificity and
      sensitivity achieved as a result of terminal protection and nucleic acid
      amplification. 

PMID- 24131015
TI  - A novel and photostable pH probe for selectively staining nuclei in living cells.
AB  - A novel pH probe based on hemi-cyanine was synthesized, which displays extremely
      large Stokes shift (122 nm) and good photostability. The probe responds to basic
      pH (pKa 8.32) with a colorimetric and fluorescence turn-on signal. Interestingly,
      the probe has good cell membrane permeability and could selectively stain nuclei
      in living cells. 

PMID- 24131017
TI  - Actin cytoskeleton control of the comings and goings of T lymphocytes.
AB  - T lymphocytes are key players of adaptive immune responses. Upon recognition of
      specific peptides presented by human leukocyte antigen (HLA) molecules on antigen
      presenting cells (APC), these cells execute subset-related functions such as
      killing, help and regulation. The ontogeny, the activation and the effector
      functions of T lymphocytes are all steps of T-lymphocyte life cycle that rely on
      high motility properties. These cells travel through the organism in a succession
      of steps, including entry into tissues, interstitial migration, APC scanning,
      synapse formation and tissue exit. Such ability is possible because of a plastic
      motility behavior, which is highly controlled in time and space. The molecular
      basis for the adaptable motility behavior of T lymphocytes is only starting to be
      unraveled. The scope of this review is to discuss recent data pointing to the key
      role of regulators of actin cytoskeleton remodeling in tuning distinct aspects of
      T-lymphocyte motility during their entry, residency and exit from tissues. 

PMID- 24131016
TI  - Postsurgical physical activity and fatigue-related daily interference in women
      with non-metastatic breast cancer.
AB  - PURPOSE: Women undergoing surgery for breast cancer experience side effects, such
      as fatigue, reduced quality of life (QOL) and depression. Physical activity (PA)
      is associated with improved psychological adjustment during treatment and
      survivorship, yet little is known about how PA relates to fatigue, depression and
      QOL in the period following surgery for breast cancer. The purpose of the study
      was to examine the relationships between these constructs in women who recently
      underwent surgery for breast cancer. METHODS: At 2-10 weeks post-surgery, 240
      women with non-metastatic breast cancer reported intensity and duration of
      moderate and vigorous PA (MVPA), fatigue (intensity and interference), depressed
      mood, clinician-rated depression and functional QOL. RESULTS: In the path
      analysis models tested, women that reported greater weekly MVPA reported less
      fatigue interference, greater functional QOL, less depressed mood, and lower
      clinician-rated depression. Tests of indirect effects suggested that fatigue
      interference may be an intermediate pathway by which MVPA relates to functional
      QOL, clinician-rated depression and depressed mood. CONCLUSION: Women who are
      more physically active in the months after breast cancer surgery show greater
      psychological adaptation in the initial phases of their treatment.

PMID- 24131018
TI  - Association of HLA-G promoter and 14-bp insertion-deletion variants with acute
      allograft rejection and end-stage renal disease.
AB  - The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D)
      polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV)
      infection, acute allograft rejection (AR) and overall survival after renal
      transplantation was investigated in 300 ESRD patients and 302 age, sex and
      ethnicity-matched controls. Sequencing was performed to evaluate the impact of
      HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi
      quantitative PCR method was used to determine the probable HLA-G expression
      pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G
      (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of
      HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion
      DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence
      interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P
      value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI =
      1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052).
      Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for
      14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased
      overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region
      sequencing was carried out among 60 ESRD patients and 100 normal controls which
      showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and 
      725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G
      transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G)
      showed increased levels in ESRD patients (mean +/- SEM; 62.16 +/- 2.43 U/ml) as
      compared to controls (mean +/- SEM; 21.06 +/- 3.89 U/ml) (P = <0.0001). The 14-bp
      I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA
      G among non-AR as compared to AR patients. 

PMID- 24131019
TI  - Characterization of Killer cell immunoglobulin-like receptor (KIR) genotypes and
      haplotypes in Chinese Han population.
AB  - We performed Killer cell immunoglobulin-like receptor (KIR) genotyping on 1271
      individuals of Chinese Han origin including 102 families and 965 unrelated
      individuals. The families (with one child and both parents) were subjected for
      haplotype analysis. Forty-one different genotypes were identified. The
      frequencies of the KIR genotypes found in the family panel were confirmed by
      those found in the unrelated panel. The family study showed segregation of one A
      haplotype and at least 15 unique B haplotypes. The most commonly observed
      haplotypes in group B were B1, B2, and B3, present at a frequency of 10.05%,
      6.62%, and 4.90%, respectively. On the basis of the combination of KIR genes, six
      centromeric and seven telomeric gene motifs have been identified. Motif cB02 was
      the most frequent haplotype B specific centromeric segment while tB01 was the
      most frequent haplotype B specific telomeric segment. The distinct distribution
      of KIR haplotypes in each population may reflect the history of directional and
      balancing selection of different races. The gene combinations of group A and
      B1/B2/B3 haplotype were the most frequent genotypes named as Bx1, Bx2, and Bx3,
      present at a frequency of 13.72%, 7.35%, and 4.41% in the family panel, and at a
      frequency of 15.86%, 10.15%, and 5.80% in the unrelated panel, respectively.
      Overall, this study showed the diversity of KIR haplotypes and genotypes in
      Chinese Han population and developed a criterion for distinguish KIR
      haplotypes/genotypes for the population. KIR genotyping and haplotype analysis
      should be useful for selection of the most optimum donor grafts with favorable
      KIR gene content for transplants. 

PMID- 24131020
TI  - Epidemiological comparison of clinical manifestations according to HLA-B*27
      carrier status of Chinese ankylosing spondylitis patients.
AB  - The aim of the study was to investigate and compare the clinical manifestations
      between HLA-B27(+) and HLA-B27(-) ankylosing spondylitis (AS) patients in order
      to obtain knowledge of the impact of HLA-B27 status on AS, and to inform clinical
      treatment. A nationwide epidemiological investigation was performed from November
      2008 to October 2010. The demographic data and clinical characteristics, and the
      status of HLA-B27 were collected using questionnaires and laboratory assay,
      respectively. A total of 2144 patients (78.5% males and 78.4% HLA-B27(+) AS
      patients) participated in this study. The percentages of males, patients with
      family history, and involvement of lumbar spine, thoracic spine and hip joints,
      were observed to be significantly higher in the HLA-B27(+) AS patients than in
      their HLA-B27(-) AS peers. 

PMID- 24131021
TI  - The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in
      patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of
      cardiovascular (CV) events. Recently, the rs964184 polymorphism has been
      associated with coronary artery disease in nonrheumatic Caucasian individuals.
      2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age
      at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and
      smoking habit) were associated with increased risk of CV events. Interestingly,
      RA patients carrying the rs964184 GG genotype had significantly higher risk of CV
      events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence
      interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at
      diagnosis and traditional CV risk factors. Our results indicate that rs964184
      polymorphism is associated with CV disease in RA. 

PMID- 24131022
TI  - Detection of a new HLA-A allele, designated HLA-A*32:53.
AB  - The novel allele A*32:53 differs from A*32:01 by a single nucleotide substitution
      in exon 4 (position 649G>A). 

PMID- 24131023
TI  - A novel HLA allele, HLA-A*80:03, identified in a Brazilian individual.
AB  - The HLA-A*80:03 allele differs from HLA*80:01:01:01 by two nucleotide
      substitutions at positions 559 and 560 in the exon 3. 

PMID- 24131024
TI  - Identification of a novel HLA-B allele, B*46:39, by sequence-based typing.
AB  - The new allele B*46:39 showed a single-nucleotide substitution compared with
      B*46:01 at codon 185 (CCA/ACA). 

PMID- 24131025
TI  - Identification of the novel HLA-C*07:315 allele.
AB  - The HLA-C*07:315 allele is mostly identical to HLA-C*07:09 but has a non
      synonymous substitution of C to G in exon 2. 

PMID- 24131026
TI  - HLA-DRB1*03:49, a novel allele identified by group-specific sequence-based typing
      in a North European individual.
AB  - Identification of the antigen presenting molecule HLA-DRB1*03:49 by group
      specific sequence-based typing. 

PMID- 24131027
TI  - Characterisation of a new HLA-DRB1 allele: DRB1*03:85.
AB  - HLA-DRB1*03:85 differs from HLA-DRB1*03:06 by two nucleotides, position 257 A>T
      and position 258T>C, resulting in Valine at codon 57. 

PMID- 24131028
TI  - Metal-ligand covalency of iron complexes from high-resolution resonant inelastic
      X-ray scattering.
AB  - Data from Kalpha resonant inelastic X-ray scattering (RIXS) have been used to
      extract electronic structure information, i.e., the covalency of metal-ligand
      bonds, for four iron complexes using an experimentally based theoretical model.
      Kalpha RIXS involves resonant 1s->3d excitation and detection of the 2p->1s
      (Kalpha) emission. This two-photon process reaches similar final states as single
      photon L-edge (2p->3d) X-ray absorption spectroscopy (XAS), but involves only
      hard X-rays and can therefore be used to get high-resolution L-edge-like spectra
      for metal proteins, solution catalysts and their intermediates. To analyze the
      information content of Kalpha RIXS spectra, data have been collected for four
      characteristic sigma-donor and pi-back-donation complexes: ferrous tacn
      [Fe(II)(tacn)2]Br2, ferrocyanide [Fe(II)(CN)6]K4, ferric tacn [Fe(III)(tacn)2]Br3
      and ferricyanide [Fe(III)(CN)6]K3. From these spectra metal-ligand covalencies
      can be extracted using a charge-transfer multiplet model, without previous
      information from the L-edge XAS experiment. A direct comparison of L-edge XAS and
      Kalpha RIXS spectra show that the latter reaches additional final states, e.g.,
      when exciting into the e(g) (sigma*) orbitals, and the splitting between final
      states of different symmetry provides an extra dimension that makes Kalpha RIXS a
      more sensitive probe of sigma-bonding. Another key difference between L-edge XAS
      and Kalpha RIXS is the pi-back-bonding features in ferro- and ferricyanide that
      are significantly more intense in L-edge XAS compared to Kalpha RIXS. This shows
      that two methods are complementary in assigning electronic structure. The Kalpha
      RIXS approach can thus be used as a stand-alone method, in combination with L
      edge XAS for strongly covalent systems that are difficult to probe by UV/vis
      spectroscopy, or as an extension to conventional absorption spectroscopy for a
      wide range of transition metal enzymes and catalysts.

PMID- 24131030
TI  - Prospective memory in Alzheimer-type dementia: exploring prospective memory
      performance in an age-stratified sample.
AB  - Prospective memory (PM), the memory for future intentions, is an essential
      component of many day-to-day activities. PM accuracy has consistently been found
      to decline as a function of age and is further impaired in Alzheimer's disease
      (AD). In the present study, subjective PM failures, PM accuracy, and cost of
      carrying a PM were recorded in 42 healthy elderly, 34 younger old, and 45 older
      old AD participants. It was found that PM deficits across the AD cohort did not
      change as a function of age. In addition, while PM accuracy was impaired compared
      to age-matched controls, cost of carrying a PM intention did not differ across
      the three groups. Evidence that AD participants show a reaction time (RT) cost of
      PM intention alongside an impaired PM accuracy indicates that the PM intention is
      held, but is not implemented effectively. The fact that the cost is independent
      of age and dementia suggests that it may not index working memory (WM) resource.
      At a practical level, the study suggests that for a comprehensive evaluation of
      PM competence cost of carrying a PM intention should be measured alongside PM
      accuracy. 

PMID- 24131031
TI  - Evaluation of MDI-spacer utilization and technique in caregivers of urban
      minority children with persistent asthma.
AB  - OBJECTIVE: Incorrect Metered-Dose Inhaler (MDI)-spacer technique can result in
      decreased drug delivery to distal airways and poor asthma outcomes. There is lack
      of research to examine whether the caregivers utilize proper technique when
      applying an MDI-spacer delivery system for young minority children with
      persistent asthma in the United States. The objective of this study was to
      evaluate MDI-spacer utilization and technique among the caregivers of Bronx
      minority children with persistent asthma and to determine characteristics
      associated with correct use. METHODS: We analyzed data from 169 caregivers of
      urban minority children with persistent asthma (aged 2-9 years). MDI-spacer
      device technique was assessed using a 10-step checklist derived from the national
      guidelines, literature and manufacturers' instructions. Based on the median MDI
      technique score of six steps demonstrated accurately, caregivers were categorized
      as correct (seven or more) or incorrect (six or less) users. RESULTS: Of the 169
      caregivers, 95% were mothers, mean age 32.3 years (SD 7.6), 56% were unemployed;
      74% of the children were Hispanic, 87% had either "not well controlled" or "very
      poorly controlled" asthma, 92% had a spacer at home and 71% used it "all" or
      "most" of the time. Only one caregiver correctly demonstrated all 10 steps of the
      MDI-spacer technique. Child's having one or more asthma-related hospitalizations
      in the past 12 months and higher caregiver educational level were independent
      predictors of correct MDI-spacer technique. CONCLUSIONS AND RELEVANCE: The
      caregivers of urban, minority children with persistent asthma lack proper MDI
      spacer technique, suggesting the potential value of both targeted short- and long
      term educational interventions.

PMID- 24131029
TI  - Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1)
      inactivators inhibit gastric cancer cell growth, invasion, and migration.
AB  - Lysine specific demethylase 1 (LSD1), the first identified histone demethylase,
      plays an important role in epigenetic regulation of gene activation and
      repression. The up-regulated LSD1's expression has been reported in several
      malignant tumors. In the current study, we designed and synthesized five series
      of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity
      toward LSD1. We found that some of these compounds, especially compound 26,
      exhibited the most specific and robust inhibition of LSD1. Interestingly,
      compound 26 also showed potent and selective cytotoxicity against LSD1
      overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked
      inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore,
      compound 26 effectively reduced the tumor growth bared by human gastric cancer
      cells in vivo with no signs of adverse side effects. These findings suggested
      that compound 26 deserves further investigation as a lead compound in the
      treatment of LSD1 overexpressing gastric cancer. 

PMID- 24131032
TI  - The association between asthma-related emergency department visits and pollen and
      mold spore concentrations in the Bronx, 2001-2008.
AB  - BACKGROUND: The incidence of asthma morbidity and mortality is highest among
      minority inner-city populations. Among New York City's five boroughs, the Bronx
      has the highest rate of asthma-related hospitalizations and mortality. Outdoor
      air pollutants have been associated with increased asthma-related ED visits
      (AREDV) in this borough. OBJECTIVE: To better understand the contribution of
      pollen and mold to asthma severity in the Bronx. METHODS: The numbers of daily
      adult and pediatric AREDV and asthma-related hospitalizations (ARH) from 2001 to
      2008 were obtained from two Bronx hospitals. AREDV and ARH data were acquired
      retrospectively through the Clinical Looking Glass data analysis software. Daily
      counts for tree, grass and weed pollen and mold spore counts from March 2001 to
      October 2008 were obtained from the Armonk counting station. All data were
      statistically analyzed and graphed as daily values. RESULTS: There were a total
      of 42 065 AREDV and 10 132 ARH at both Bronx hospitals. There were spring and
      winter peaks of increased AREDV. Tree pollen counts significantly correlated with
      total AREDV (rho = 0.3639, p < 0.001), and pediatric (rho = 0.33, p < 0.001) and
      adult AREDV (rho = 0.28, p < 0.001). ARH positively correlated with tree pollen
      counts (Spearman rho = 0.2389, p < 0.001). CONCLUSIONS: There exists a
      significant association between spring AREDV and ARH and tree pollen
      concentrations in a highly urbanized area such as the Bronx. Early anticipation
      of spring pollen peaks based on ongoing surveillance could potentially guide
      clinical practice and minimize asthma-related ED visits in the Bronx.

PMID- 24131033
TI  - Small molecule inhibitors of PIM1 kinase: July 2009 to February 2013 patent
      update.
AB  - INTRODUCTION: The proviral insertion in murine (PIM) lymphoma proteins for which
      three isoforms, PIM1, PIM2 and PIM3 have been identified, belonging to the family
      of serine/threonine kinases has emerged recently as an important therapeutic
      target for the development of selective inhibitors as the new drugs for treating
      hematological malignancies and solid tumors. The small molecules developed by
      academia and the pharmaceutical industry have steadily increased in the last few
      years. Several drug discovery groups focus on treating disorders, such as cancer
      mediated by PIM kinase, have provided preclinical evidence suggesting that PIM
      inhibitor provides anti-apoptotic activity, inhibit cell survival and cell
      proliferation. AREAS COVERED: This article discloses recent reviews on research
      and advances published in the patent literature and scientific publications from
      July 2009 to February 2013, highlighting discoveries on PIM1 kinase. EXPERT
      OPINION: Several PIM1 kinase small molecule inhibitors are now at the pre
      clinical research stage, development and testing. Though nearly 40 patents
      emerged in the last 3 years, greater efforts towards additional designs and
      medicinal chemistry continues for developing clinically efficacious PIM1
      inhibitors, due to the significance of the target for cancer and the potential
      for novel and diverse inhibitors as drug candidates.

PMID- 24131034
TI  - Getting published well requires fulfilling editors' and reviewers' needs and
      desires.
AB  - Publication in international scientific journals provides an unparalleled
      opportunity for authors to showcase their work. Where authors publish affects how
      the community values the work. This value directly determines the impact of the
      work on the field-papers must be read and cited to advance the field, and because
      the scientific literature is vast, only a subset of the literature is widely read
      and cited. Moreover, the value placed on the work also affects the authors'
      scientific reputation and career advancement. Consequently, it is essential that
      manuscripts receive the recognition they deserve by being published in one of the
      "best" journals that the scientific findings allow. Several factors determine
      where a paper is published: how well the topic of the paper fits the scope of the
      journal, the quality of the study and the manuscript describing it, the advance
      the paper makes in its field, the importance of the advance, and the extent to
      which the paper impacts the broader community of science. As scientists, we
      assume that our papers will be assessed objectively using only well defined
      scientific standards, but editors and reviewers also view papers subjectively,
      having biases of what defines a high-quality publication based on Western
      standards. Therefore, scientists trained in other parts of the world can be
      significantly disadvantaged in getting their papers published in the best
      journals. Here, I present concrete suggestions for improving the perception of a
      paper in the reader's minds, increasing the likelihood that it will get published
      well. 

PMID- 24131035
TI  - Social identification moderates cognitive health and well-being following story-
      and song-based reminiscence.
AB  - OBJECTIVES: Reminiscence is a popular intervention for seniors, but, with mixed
      evidence supporting its efficacy, questions have been raised about the mechanisms
      underlying improvement. The present paper addresses this question by
      investigating the degree to which health effects depend on the development of a
      shared sense of group identification. This is examined in the context of
      traditional story-based reminiscence as well as novel forms of song-based
      reminiscence. METHOD: As the focus of a manualized intervention, 40 participants
      were randomly assigned to secular song (n=13), religious song (n=13), or standard
      story reminiscence (n=14) groups. These were run over six weeks with cognitive
      performance, anxiety, and life satisfaction measured before and after the
      intervention. Measures of group fit were included to examine whether social
      identification contributed to outcomes. RESULTS: No evidence of change emerged
      over time as a function of intervention form alone, but analysis of
      identification data revealed significant interactions with the type of
      reminiscence group. Specifically, initial fit with the story reminiscence group
      was associated with enhanced cognitive outcomes and greater life satisfaction,
      while fit with the religious song reminiscence group was associated with greater
      life satisfaction and less anxiety. CONCLUSION: These findings show that group
      identification is a key moderator through which reminiscence promotes health
      outcomes. Implications for theory and practice highlight an inherent limitation
      in randomized controlled trials insofar as they may compromise participants'
      group identification.

PMID- 24131036
TI  - Synthesis of N-substituted pyrido[4,3-d]pyrimidines for the large-scale
      production of self-assembled rosettes and nanotubes.
AB  - N-substituted pyrido[4,3-d]pyrimidines are heterocycles which exhibit the
      asymmetric hydrogen bonding codes of both guanine and cytosine at 60 degrees 
      angles to each other, such that the molecules self-organize unambiguously into a
      cyclic hexamer, assembled via 18 intermolecular hydrogen bonds. The synthesis is
      straightforward and can be concluded in six steps from the commercially available
      malononitrile dimer. X-ray crystallographic analysis of the supermacrocyclic
      structure shows an undulating disk with a ca. 10.5 A cavity, the centers of which
      do not overlap sufficiently to describe a channel in the solid state. However,
      AFM, SEM, and TEM imaging in solution reveals the formation of 1D nanostructures
      in agreement with their self-assembly into rosette supermacrocycles, which then
      stack linearly to form rosette nanotubes. 

PMID- 24131037
TI  - Post-myocardial infarction ventricular septal defect.

PMID- 24131038
TI  - Cp*Co(III) catalysts with proton-responsive ligands for carbon dioxide
      hydrogenation in aqueous media.
AB  - New water-soluble pentamethylcyclopentadienyl cobalt(III) complexes with proton
      responsive 4,4'- and 6,6'-dihydroxy-2,2'-bipyridine (4DHBP and 6DHBP,
      respectively) ligands have been prepared and were characterized by X-ray
      crystallography, UV-vis and NMR spectroscopy, and mass spectrometry. These
      cobalt(III) complexes with proton-responsive ligands predominantly exist in their
      deprotonated [Cp*Co(DHBP-2H(+))(OH2)] forms with stronger electron-donating
      properties in neutral and basic solutions, and are active catalysts for CO2
      hydrogenation in aqueous bicarbonate media at moderate temperature under a total
      4-5 MPa (CO2:H2 1:1) pressure. The cobalt complexes containing 4DHBP ligands ([1
      OH2](2+) and [1-Cl](+), where 1 = Cp*Co(4DHBP)) display better thermal stability
      and exhibit notable catalytic activity for CO2 hydrogenation to formate in
      contrast to the catalytically inactive nonsubstituted bpy analogues [3-OH2](2+)
      (3 = Cp*Co(bpy)). While the catalyst Cp*Ir(6DHBP)(OH2)(2+) in which the pendent
      oxyanion lowers the barrier for H2 heterolysis via proton transfer through a
      hydrogen-bonding network involving a water molecule is remarkably effective (ACS
      Catal. 2013, 3, 856-860), cobalt complexes containing 6DHBP ligands ([2-OH2](2+)
      and [2-Cl](+), 2 = Cp*Co(6DHBP)) exhibit lower TOF and TON for CO2 hydrogenation
      than those with 4DHBP. The low activity is attributed to thermal instability
      during the hydrogenation of CO2 as corroborated by DFT calculations. 

PMID- 24131039
TI  - Review: Neuropathological features of unexplained sudden unexpected death in
      infancy: current evidence and controversies.
AB  - Sudden infant death syndrome (SIDS) is a leading cause of postneonatal infant
      death in the developed world. The cause of SIDS is unknown but several hypotheses
      have been proposed, including the 'triple risk hypothesis', which predicts that
      foetal development of infants who subsequently succumb to SIDS is abnormal,
      leaving them unable to respond appropriately to stressors. Consistent with this
      hypothesis, a large number of studies have reported changes in the brain in SIDS.
      However, on nearly every subject, the reported findings vary widely between
      studies. Inconsistencies in the definitions of SIDS used and in control group
      selection are likely to underlie much of this variability. Therefore, in our
      analysis, we have included only those studies that met simple criteria for both
      the definition of SIDS and the control group. Of the 153 studies retrieved by our
      review of the literature, 42 (27%) met these criteria. Foremost among the
      findings reported by these studies are abnormalities of the brain stem, in
      particular brain stem gliosis and defects of neurotransmission in the medulla.
      However, these studies have not identified what could be considered in diagnostic
      terms a causative structural or biochemical abnormality for use in routine
      clinical practice. An assessment of changes in the architecture and composition
      of brain regions and changes in neurotransmission in multiple systems in a
      single, large cohort of well- and consistently characterized infants dying
      suddenly of a range of causes is needed before the inter-relation of these
      different features can be appreciated. 

PMID- 24131040
TI  - Measurements of individual radiation doses in residents living around the
      Fukushima Nuclear Power Plant.
AB  - At the outset of the accident at Fukushima Daiichi Nuclear Power Plant in March
      2011, the radiation doses experienced by residents were calculated from the
      readings at monitoring posts, with several assumptions being made from the point
      of view of protection and safety. However, health effects should also be
      estimated by obtaining measurements of the individual radiation doses. The
      individual external radiation doses, determined by a behavior survey in the
      "evacuation and deliberate evacuation area" in the first 4 months, were <5 mSv in
      97.4% of residents (maximum: 15 mSv). Doses in Fukushima Prefecture were <3 mSv
      in 99.3% of 386,572 residents analyzed. External doses in Fukushima City
      determined by personal dosimeters were <1 mSv/3 months (September-November, 2011)
      in 99.7% of residents (maximum: 2.7 mSv). Thyroid radiation doses, determined in
      March using a NaI (TI) scintillation survey meter in children in the evacuation
      and deliberate evacuation area, were <10 mSv in 95.7% of children (maximum: 35
      mSv). Therefore, all doses were less than the intervention level of 50 mSv
      proposed by international organizations. Internal radiation doses determined by
      cesium-134 ((134)C) and cesium-137 ((137)C) whole-body counters (WBCs) were <1
      mSv in 99% of the residents, and the maximum thyroid equivalent dose by iodine
      131 WBCs was 20 mSv. The exploratory committee of the Fukushima Health Management
      Survey mentions on its website that radiation from the accident is unlikely to be
      a cause of adverse health effects in the future. In any event, sincere scientific
      efforts must continue to obtain individual radiation doses that are as accurate
      as possible. However, observation of the health effects of the radiation doses
      described above will require reevaluation of the protocol used for determining
      adverse health effects. The dose-response relationship is crucial, and the aim of
      the survey should be to collect sufficient data to confirm the presence or
      absence of radiation health effects. In particular, the schedule of
      decontamination needs reconsideration. The decontamination map is determined
      based on the results of airborne monitoring and the radiation dose calculated
      from readings taken at the monitoring posts at the initial period of the
      accident. The decontamination protocol should be reevaluated based on the
      individual doses of the people who desire to live in those areas. 

PMID- 24131041
TI  - Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if
      started 35 days after whole-thorax irradiation.
AB  - Victims of a radiological attack or nuclear accident may receive high-dose,
      heterogeneous exposures from radiation to the chest that lead to lung damage. Our
      goal is to develop countermeasures to mitigate such injuries. We used WAG/RijCmcr
      rats receiving 13 Gy to the whole thorax to induce pulmonary fibrosis within 210
      days. The angiotensin converting enzyme (ACE) inhibitor enalapril was evaluated
      as a mitigator of these injuries at two doses (18 and 36 mg/m(2)/day) and 8
      schedules: starting at 7, 35, 70, 105 and 140 days and continuing to 210 days or
      starting at 7 days and stopping at 30, 60 or 90 days after whole-thorax
      irradiation. The earliest start date at 7 days after irradiation would provide an
      adequate window of time for triage and dosimetry. Survival after 35 days, as
      permitted by our Institutional Animal Care and Use Committee (IACUC) was also
      recorded as a primary end point of pneumonitis. Pulmonary fibrosis was evaluated
      using the Sircol biochemical assay to measure lung collagen. Our results
      indicated that a short course of either dose of enalapril from 7-90 days improved
      survival. However, pulmonary fibrosis was only mitigated by the higher dose of
      enalapril (36 mg/m(2)/day). The latest effective start date for the drug was 35
      days after irradiation. These results indicate that ACE inhibitors can be started
      at least a month after irradiation for mitigation of pneumonitis and/or pulmonary
      fibrosis. 

PMID- 24131042
TI  - The temporal dynamics of cognitive reappraisal: cardiovascular consequences of
      downregulation of negative emotion and upregulation of positive emotion.
AB  - This study examines the effects of cognitive reappraisal on the cardiovascular
      response to affective stimuli. Participants (N = 53) were shown affective images
      and were asked either to attend to the images, or to downregulate negative affect
      through reappraisal of negative images or upregulate positive affect through
      reappraisal of positive images while continuous measures of cardiovascular
      activity were recorded. Reappraisal of negative images was associated with lower
      total peripheral resistance and larger cardiac output in the prestimulus period,
      whereas reappraisal of positive images was associated with less pronounced
      decreases of heart rate, cardiac output, and mean blood pressure in the viewing
      period as compared to unregulated conditions. The results indicate that cognitive
      reappraisal engenders adaptive hemodynamic profiles both during anticipation and
      during viewing of affective images depending on their valence and the regulatory
      goal.

PMID- 24131043
TI  - Patient participation, decision-makers and information flow in surgical
      treatment.
AB  - AIMS AND OBJECTIVES: To clarify patient participation by specifying three kinds
      of information flows between healthcare professionals and patients in four models
      such as the paternalistic, shared, informed and nonpaternalistic models.
      BACKGROUND: The relationship between healthcare professionals and patients has
      evolved from a traditional paternalistic model where 'doctors know best' and
      patients are passive recipients, to a partnership where patients act as active
      participants. DESIGN: A qualitative study. METHODS: Qualitative data from
      interviews with four doctors, seven nurses and seven patients illustrate these
      relationships. RESULTS: A 3 * 3 matrix is developed where healthcare
      professionals can make decisions unilaterally, patients can make decisions
      unilaterally, or these can make decisions jointly. Information can flow from
      healthcare professionals to patient, from patient to healthcare professionals or
      both ways. CONCLUSIONS: This conceptualisation provides a rich understanding of
      decision-making and information flow in surgical hospitals. RELEVANCE TO CLINICAL
      PRACTICE: The paper illustrates how practice can be assessed empirically to
      determine how it fits into the structure. Strategies can be implemented to move
      practice from one part of the structure to another part.

PMID- 24131044
TI  - Endophthalmitis following keratoplasty: incidence, microbial profile, visual and
      structural outcomes.
AB  - PURPOSE: To identify the causative organisms of post-keratoplasty endophthalmitis
      and to report its visual and structural outcomes. METHODS: A chart review was
      performed of all patients diagnosed with endophthalmitis after keratoplasty at a
      tertiary hospital between January 1990 and January 2007. RESULTS: Endophthalmitis
      developed in 55 cases in the penetrating keratoplasty group and in no cases in
      the lamellar keratoplasty group. The majority of isolated microbes were gram
      positive (86.3%). Only 1 eye retained a clear graft with 20/25 vision; other
      cases had <=20/200 vision. Four of 13 eyes that underwent vitrectomy and 28 of 42
      that did not undergo vitrectomy ended up with no light perception. One eye that
      underwent vitrectomy and 21 eyes that did not undergo vitrectomy were
      eviscerated. CONCLUSIONS: Post-keratoplasty endophthalmitis was associated with
      poor visual and structural outcome. Gram-positive organisms were the most common
      cause of infection. Early vitrectomy may reduce functional and structural damage
      associated with endophthalmitis.

PMID- 24131045
TI  - The effect of in-home cognitive training on functional performance of individuals
      with mild cognitive impairment and early-stage Alzheimer's disease.
AB  - This intervention study compared an in-home cognitive training program to life
      story interview in 68 individuals with mild cognitive impairment or early-stage
      Alzheimer's disease. Family caregivers participated in sessions and reinforced
      learning between sessions. Analyses of covariance controlling for baseline levels
      were conducted. In comparison with the life story group, participants in the
      cognitive training group demonstrated significant improvement in all face-name
      association measures, several of the money-related tasks, and one of two event
      related memory tasks. There were no differences in language outcomes or caregiver
      ratings of functional tasks except shopping. Caregivers in the life story group
      reported higher perceived satisfaction from being a caregiver. Comparison with
      earlier studies suggests in-home training is modestly more effective than office
      based intervention. Results suggest that improvements are related to specific
      training and do not generalize to other tasks. Focusing on tasks of critical
      significance to participant and caregiver is recommended.

PMID- 24131046
TI  - Evaluation of corneal biomechanical properties in patients with rheumatoid
      arthritis: a study by ocular response analyzer.
AB  - PURPOSE: To compare the corneal biomechanical properties of rheumatoid arthritis
      (RA) patients with those of healthy controls. METHODS: Measurements of 39 eyes of
      39 RA patients (patient group) were compared with those of 55 eyes of 55 healthy
      controls (control group). Corneal hysteresis (CH), corneal resistance factor
      (CRF), intraocular pressure (IOP), and corneal-compensated IOP (IOPcc) were
      obtained for each subject by the ocular response analyzer (ORA). Corneal
      thickness (CCT) was measured by ultrasonic pachymeter. RESULTS: CH and CRF were
      significantly lower in the patient group than in the control group (p1 = 0.002,
      p2 = 0.019, respectively). The patient group had significantly higher IOPcc
      values than the control group (p = 0.024). There was no significant differences
      between the groups concerning CCT and IOP. CONCLUSIONS: RA patients had lower CH
      and CRF, but higher IOPcc values than healthy controls. RA should be considered
      when the corneal biomechanical properties measured by the ORA are used for
      diagnoses or therapies.

PMID- 24131047
TI  - Mere exposure effect can be elicited in transient global amnesia.
AB  - Transient global amnesia (TGA) is one of the most severe forms of anterograde
      amnesia seen in clinical practice, yet patients may show evidence of spared
      learning during the amnesic episode. The scope of spared learning in such a
      severe form of amnesia remains uncertain, and it is also unclear whether findings
      from single-case studies hold up in group studies of TGA patients. In this group
      study, we found evidence that extended the domain of spared learning in TGA to
      include the mere exposure effect, whereby enhanced preference is primed by prior
      exposure to stimuli. We demonstrate this effect during an acute episode in a
      group of TGA patients, where they showed enhanced preference for previously
      exposed faces, despite markedly impaired performance on standard anterograde
      memory tests. 

PMID- 24131048
TI  - Foreword to the special issue on selected papers from the 5th International
      Conference on Bioinformatics and Computational Biology (BICoB 2013).

PMID- 24131049
TI  - When cloud computing meets bioinformatics: a review.
AB  - In the past decades, with the rapid development of high-throughput technologies,
      biology research has generated an unprecedented amount of data. In order to store
      and process such a great amount of data, cloud computing and MapReduce were
      applied to many fields of bioinformatics. In this paper, we first introduce the
      basic concepts of cloud computing and MapReduce, and their applications in
      bioinformatics. We then highlight some problems challenging the applications of
      cloud computing and MapReduce to bioinformatics. Finally, we give a brief
      guideline for using cloud computing in biology research. 

PMID- 24131050
TI  - Dynamic Bayesian clustering.
AB  - Clusters of time series data may change location and memberships over time; in
      gene expression data, this occurs as groups of genes or samples respond
      differently to stimuli or experimental conditions at different times. In order to
      uncover this underlying temporal structure, we consider dynamic clusters with
      time-dependent parameters which split and merge over time, enabling cluster
      memberships to change. These interesting time-dependent structures are useful in
      understanding the development of organisms or complex organs, and could not be
      identified using traditional clustering methods. In cell cycle data, these time
      dependent structure may provide links between genes and stages of the cell cycle,
      whilst in developmental data sets they may highlight key developmental
      transitions. 

PMID- 24131051
TI  - CNCTDiscriminator: coding and noncoding transcript discriminator - an excursion
      through hypothesis learning and ensemble learning approaches.
AB  - The statistics about the open reading frames, the base compositions and the
      properties of the predicted secondary structures have potential to address the
      problem of discriminating coding and noncoding transcripts. Again, the Next
      Generation Sequencing platform, RNA-seq, provides us bounty of data from which
      expression profiles of the transcripts can be extracted which urged us adding a
      new set of dimension in this classification task. In this paper, we proposed
      CNCTDiscriminator -- a coding and noncoding transcript discriminating system
      where we applied the integration of these four categories of features about the
      transcripts. The feature integration was done using both hypothesis learning and
      feature specific ensemble learning approaches. The CNCTDiscriminator model which
      was trained with composition and ORF features outperforms (precision 83.86%,
      recall 82.01%) other three popular methods -- CPC (precision 98.31%, recall
      25.95%), CPAT (precision 97.74%, recall 52.50%) and PORTRAIT (precision 84.37%,
      recall 73.2%) when applied to an independent benchmark dataset. However, the
      CNCTDiscriminator model that was trained using the ensemble approach shows
      comparable performance (precision 89.85%, recall 71.08%).

PMID- 24131052
TI  - Studying the role of ApoE in Alzheimer's disease pathogenesis using a systems
      biology model.
AB  - Alzheimer's disease (AD) is the most common form of dementia. Even with its well
      known symptoms of memory loss and well-characterized pathology of beta amyloid
      (Abeta) plaques and neurofibrillary tangles, the disease pathogenesis and
      initiating factors are still not well understood. To tackle this problem, a
      systems biology model has been developed and used to study the varying effects of
      variations in the ApoE allele present, as well as the effects of short term and
      periodic inflammation at low to moderate levels. Simulations showed a late onset
      peak of Abeta in the ApoE4 case that lead to localized neuron loss which could be
      ameliorated in part by application of short-term pro-inflammatory mediators. The
      model that has been developed herein represents one of the first attempts to
      model AD from a systems approach to study physiologically relevant parameters
      that may prove useful to physicians in the future. 

PMID- 24131053
TI  - A hybrid-system model of the coagulation cascade: simulation, sensitivity, and
      validation.
AB  - The process of human blood clotting involves a complex interaction of continuous
      time/continuous-state processes and discrete-event/discrete-state phenomena,
      where the former comprise the various chemical rate equations and the latter
      comprise both threshold-limited behaviors and binary states (presence/absence of
      a chemical). Whereas previous blood-clotting models used only continuous dynamics
      and perforce addressed only portions of the coagulation cascade, we capture both
      continuous and discrete aspects by modeling it as a hybrid dynamical system. The
      model was implemented as a hybrid Petri net, a graphical modeling language that
      extends ordinary Petri nets to cover continuous quantities and continuous-time
      flows. The primary focus is simulation: (1) fidelity to the clinical data in
      terms of clotting-factor concentrations and elapsed time; (2) reproduction of
      known clotting pathologies; and (3) fine-grained predictions which may be used to
      refine clinical understanding of blood clotting. Next we examine sensitivity to
      rate-constant perturbation. Finally, we propose a method for titrating between
      reliance on the model and on prior clinical knowledge. For simplicity, we confine
      these last two analyses to a critical purely-continuous subsystem of the model. 

PMID- 24131054
TI  - Exact solutions for species tree inference from discordant gene trees.
AB  - Phylogenetic analysis has to overcome the grant challenge of inferring accurate
      species trees from evolutionary histories of gene families (gene trees) that are
      discordant with the species tree along whose branches they have evolved. Two well
      studied approaches to cope with this challenge are to solve either biologically
      informed gene tree parsimony (GTP) problems under gene duplication, gene loss,
      and deep coalescence, or the classic RF supertree problem that does not rely on
      any biological model. Despite the potential of these problems to infer credible
      species trees, they are NP-hard. Therefore, these problems are addressed by
      heuristics that typically lack any provable accuracy and precision. We describe
      fast dynamic programming algorithms that solve the GTP problems and the RF
      supertree problem exactly, and demonstrate that our algorithms can solve
      instances with data sets consisting of as many as 22 taxa. Extensions of our
      algorithms can also report the number of all optimal species trees, as well as
      the trees themselves. To better asses the quality of the resulting species trees
      that best fit the given gene trees, we also compute the worst case species trees,
      their numbers, and optimization score for each of the computational problems.
      Finally, we demonstrate the performance of our exact algorithms using empirical
      and simulated data sets, and analyze the quality of heuristic solutions for the
      studied problems by contrasting them with our exact solutions. 

PMID- 24131055
TI  - A peak alignment algorithm with novel improvements in application to
      electropherogram analysis.
AB  - Alignment of peaks in electropherograms or chromatograms obtained from
      experimental techniques such capillary electrophoresis remains a significant
      challenge. Accurate alignment is critical for accurate interpretation of various
      classes of nucleic acid analysis technologies, including conventional DNA
      sequencing and new RNA structure probing technologies. An automated alignment
      algorithm was developed based on dynamic programming to align multiple-peak time
      series data both globally and locally. This algorithm relies on a new peak
      similarity measure and other features such as time penalties, global constraints,
      and minimum-similarity scores and results in rapid, highly accurate comparisons
      of complex time-series datasets. As a demonstrative case study, the developed
      algorithm was applied to analysis of capillary electrophoresis data from a
      Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) evaluation
      of RNA secondary structure. The algorithm yielded robust analysis of challenging
      SHAPE probing data. Experimental results show that the peak alignment algorithm
      corrects retention time variation efficiently due to the presence of fluorescent
      tags on fragments and differences in capillaries. The tools can be readily
      adapted for the analysis other biological datasets in which peak retention times
      vary. 

PMID- 24131056
TI  - Prediction of protein secondary structure using probability based features and a
      hybrid system.
AB  - In this paper, we propose some co-occurrence probability-based features for
      prediction of protein secondary structure. The features are extracted using
      occurrence/nonoccurrence of secondary structures in the protein sequences. We
      explore two types of features: position-specific (based on position of amino acid
      on fragments of protein sequences) as well as position-independent (independent
      of amino acid position on fragments of protein sequences). We use a hybrid
      system, NEUROSVM, consisting of neural networks and support vector machines for
      classification of secondary structures. We propose two schemes NSVMps and NSVM
      for protein secondary structure prediction. The NSVMps uses position-specific
      probability-based features and NEUROSVM classifier whereas NSVM uses the same
      classifier with position-independent probability-based features. The proposed
      method falls in the single-sequence category of methods because it does not use
      any sequence profile information such as position specific scoring matrices
      (PSSM) derived from PSI-BLAST. Two widely used datasets RS126 and CB513 are used
      in the experiments. The results obtained using the proposed features and NEUROSVM
      classifier are better than most of the existing single-sequence prediction
      methods. Most importantly, the results using NSVMps that are obtained using lower
      dimensional features, are comparable to those by other existing methods. The
      NSVMps and NSVM are finally tested on target proteins of the critical assessment
      of protein structure prediction experiment-9 (CASP9). A larger dataset is used to
      compare the performance of the proposed methods with that of two recent single
      sequence prediction methods. We also investigate the impact of presence of
      different amino acid residues (in protein sequences) that are responsible for the
      formation of different secondary structures. 

PMID- 24131058
TI  - The next generation of similarity measures that fully explore the semantics in
      biomedical ontologies.
AB  - There is a prominent trend to augment and improve the formality of biomedical
      ontologies. For example, this is shown by the current effort on adding
      description logic axioms, such as disjointness. One of the key ontology
      applications that can take advantage of this effort is the conceptual
      (functional) similarity measurement. The presence of description logic axioms in
      biomedical ontologies make the current structural or extensional approaches
      weaker and further away from providing sound semantics-based similarity measures.
      Although beneficial in small ontologies, the exploration of description logic
      axioms by semantics-based similarity measures is computational expensive. This
      limitation is critical for biomedical ontologies that normally contain thousands
      of concepts. Thus in the process of gaining their rightful place, biomedical
      functional similarity measures have to take the journey of finding how this rich
      and powerful knowledge can be fully explored while keeping feasible computational
      costs. This manuscript aims at promoting and guiding the development of
      compelling tools that deliver what the biomedical community will require in a
      near future: a next-generation of biomedical similarity measures that efficiently
      and fully explore the semantics present in biomedical ontologies. 

PMID- 24131057
TI  - Heuristics for the transposition distance problem.
AB  - Transpositions are large-scale mutational events that occur when a block of genes
      moves from a region of a chromosome to another region within the same chromosome.
      The transposition distance problem is the minimum number of transpositions
      required to transform one genome into another. Recently, Bulteau et al. [Bulteau
      L, Fertin G, Rusu U, Automata, Languages and Programming, Vol. 6755 of Lecture
      Notes in Computer Science, pp. 654-665, Springer Berlin, Heidelberg, 2011] proved
      that finding the transposition distance is a NP-Hard problem. Some approximation
      algorithm for this problem have been presented to date [Bafna V, Pevzner PA, SIAM
      J Discr Math11(2):224-240, 1998; Elias I, Hartman T, IEEE/ACM Trans Comput Biol
      Bioinform3(4):369-379, 2006; Mira CVG, Dias Z, Santos HP, Pinto GA, Walter ME,
      Proc 3rd Brazilian Symp Bioinformatics (BSB'2008), pp. 115-126, Santo Andre,
      Brazil, 2008; Walter MEMT, Dias Z, Meidanis J, Proc String Processing and
      Information Retrieval (SPIRE'2000), pp. 199-208, Coruna, Spain, 2000]. Here we
      focus on developing heuristics to provide an improved approximated solution. Our
      approach outperforms other algorithms on small sized permutations. We also show
      that our algorithm keeps the good performance on longer permutations. 

PMID- 24131059
TI  - New developments around histamine H(3) receptor antagonists/inverse agonists: a
      patent review (2010 - present).
AB  - INTRODUCTION: Histamine H3 receptor (H3R) is involved in the central and
      peripheral regulation of levels of histamine and other neurotransmitters (e.g.,
      acetylcholine, noradrenaline, dopamine or serotonin). H3R antagonists/inverse
      agonists constitute attractive targets in the search for new drugs. Preclinical
      data indicate their potential utility in the treatment of various central nervous
      system (CNS), metabolic, pain and allergic disorders. So far, many structurally
      diverse H3R ligands have been synthesized and pharmacologically evaluated.
      Certain compounds have reached clinical trials. The first results from these
      studies have appeared. AREAS COVERED: The literature covering patent applications
      (2010 through June 2013) found in the Espacenet database will be reported. EXPERT
      OPINION: In comparison with previous years, recently the number of patent
      applications concerning H3R antagonists/inverse agonists has decreased. The
      utility of compounds is still being verified in pharmacological studies. The
      first published results from clinical trials have shown not only positive effects
      but also emerging drawbacks. So far, BF2.649 is the most advanced in human trials
      (tiprolisant; Phase III trials). New ligands are being intensively tested in
      preclinical tests. Thus, it is expected that they will soon undergo clinical
      trials.

PMID- 24131060
TI  - The distressed (Type D) personality mediates the relationship between remembered
      parenting and psychological distress in cardiac patients.
AB  - OBJECTIVE: Both the distressed (Type D) personality (i.e. the combination of
      negative affectivity and social inhibition traits) and dysfunctional parenting
      styles are associated with anxiety and depression. As parenting styles have been
      related to personality development, dysfunctional parenting styles may also be
      associated with Type D personality. We examined whether remembered parenting was
      associated with anxiety and depression in cardiac patients and whether Type D
      personality mediated this relationship. METHODS: Our sample comprised 435
      patients treated with percutaneous coronary intervention (PCI) and 123 patients
      with congestive heart failure (CHF). Patients completed the Hospital Anxiety and
      Depression Scale, Type D Scale (DS14), and Remembered Relationship with Parents
      (RRP(10)) scale. RESULTS: Remembered parenting was significantly associated with
      higher anxiety and depression levels and Type D personality. In multivariable
      linear regression analyses, Type D personality accounted for 25-29% of the
      variance in anxiety and 23-46% of the variance in depression, while remembered
      parenting was no longer significantly associated with these domains. Sobel tests
      and bootstrapping indicated that Type D personality mediated the relationship
      between remembered parenting and anxiety and depression. CONCLUSION: Type D
      personality mediated the relationship between remembered parenting and anxiety
      and depression in both PCI and CHF patients.

PMID- 24131061
TI  - Quality palliative care for cancer and dementia in five European countries: some
      common challenges.
AB  - OBJECTIVES: There is a growing consensus worldwide that palliative care needs to
      be both more inclusive of conditions other than cancer and to improve. This paper
      explores some common challenges currently faced by professionals providing
      palliative care for patients with either cancer or dementia across five
      countries. METHOD: One focus group (n=7) and 67 interviews were conducted in 2012
      across five countries: England, Germany, Italy, the Netherlands and Norway, with
      professionals from dementia, cancer and palliative care settings. RESULTS: The
      interviews revealed five common challenges faced across the five countries:
      communication difficulties (between services; and between professionals, and
      patients and their families); the variable extent of structural/functional
      integration of services; the difficulties in funding of palliative care services;
      problematic processes of care (boundaries, definitions, knowledge, skills and
      inclusiveness) and, finally, time constraints. CONCLUSION: These are not problems
      distinct to palliative care, but they may have different origins and explanations
      compared to other areas of health care. This paper explored deeper themes hidden
      behind a discourse about barriers and facilitators to improving care.

PMID- 24131062
TI  - Inelastic cross sections for low-energy electrons in liquid water: exchange and
      correlation effects.
AB  - Low-energy electrons play a prominent role in radiation therapy and biology as
      they are the largest contributor to the absorbed dose. However, no tractable
      theory exists to describe the interaction of low-energy electrons with condensed
      media. This article presents a new approach to include exchange and correlation
      (XC) effects in inelastic electron scattering at low energies (below ~10 keV) in
      the context of the dielectric theory. Specifically, an optical-data model of the
      dielectric response function of liquid water is developed that goes beyond the
      random phase approximation (RPA) by accounting for XC effects using the concept
      of the many-body local-field correction (LFC). It is shown that the experimental
      energy-loss-function of liquid water can be reproduced by including into the RPA
      dispersion relations XC effects (up to second order) calculated in the time
      dependent local-density approximation with the addition of phonon-induced
      broadening in N. D. Mermin's relaxation-time approximation. Additional XC effects
      related to the incident and/or struck electrons are included by means of the
      vertex correction calculated by a modified Hubbard formula for the exchange-only
      LFC. Within the first Born approximation, the present XC corrections cause a
      significantly larger reduction (~10-50%) to the inelastic cross section compared
      to the commonly used Mott and Ochkur approximations, while also yielding much
      better agreement with the recent experimental data for amorphous ice. The current
      work offers a manageable, yet rigorous, approach for including non-Born effects
      in the calculation of inelastic cross sections for low-energy electrons in liquid
      water, which due to its generality, can be easily extended to other condensed
      media. 

PMID- 24131063
TI  - Divergent modification of low-dose 56Fe-particle and proton radiation on skeletal
      muscle.
AB  - It is unknown whether loss of skeletal muscle mass and function experienced by
      astronauts during space flight could be augmented by ionizing radiation (IR),
      such as low-dose high-charge and energy (HZE) particles or low-dose high-energy
      proton radiation. In the current study adult mice were irradiated whole-body with
      either a single dose of 15 cGy of 1 GeV/n 56Fe-particle or with a 90 cGy proton
      of 1 GeV/n proton particles. Both ionizing radiation types caused alterations in
      the skeletal muscle cytoplasmic Ca2+ ([Ca2+]i) homeostasis. 56Fe-particle
      irradiation also caused a reduction of depolarization-evoked Ca2+ release from
      the sarcoplasmic reticulum (SR). The increase in the [Ca2+]i was detected as
      early as 24 h after 56Fe-particle irradiation, while effects of proton
      irradiation were only evident at 72 h. In both instances [Ca2+]i returned to
      baseline at day 7 after irradiation. All 56Fe-particle irradiated samples
      revealed a significant number of centrally localized nuclei, a histologic
      manifestation of regenerating muscle, 7 days after irradiation. Neither
      unirradiated control or proton-irradiated samples exhibited such a phenotype.
      Protein analysis revealed significant increase in the phosphorylation of Akt,
      Erk1/2 and rpS6k on day 7 in 56Fe-particle irradiated skeletal muscle, but not
      proton or unirradiated skeletal muscle, suggesting activation of pro-survival
      signaling. Our findings suggest that a single low-dose 56Fe-particle or proton
      exposure is sufficient to affect Ca2+ homeostasis in skeletal muscle. However,
      only 56Fe-particle irradiation led to the appearance of central nuclei and
      activation of pro-survival pathways, suggesting an ongoing muscle damage/recovery
      process.

PMID- 24131065
TI  - Treatment of striae distensae using an ablative Erbium: YAG fractional laser
      versus a 585-nm pulsed-dye laser.
AB  - Abstract Striae distensae (SD) represent a common disfiguring cutaneous condition
      characterized by linear reddish smooth bands of atrophic-appearing skin. Most
      often SD develop in areas of dermal damage produced by stretching. Numerous
      treatment modalities have been applied with varying success. Novel approaches
      include treatments with various types of lasers with the flashlamp-pumped pulsed
      dye laser (PDL; 585 nm) being the most commonly reported. Very recently,
      fractional photothermolysis has been suggested as an effective method for the
      treatment of SD. Here, we report on the effect of an ablative Erbium:YAG
      fractional laser in two cases of axillary SD in comparison with a 585-nm PDL. 

PMID- 24131064
TI  - Education level predicts retrospective metamemory accuracy in healthy aging and
      Alzheimer's disease.
AB  - The current study investigated the effect of education on retrospective
      metamemory accuracy in 143 healthy older adults and 143 early to moderate
      Alzheimer's disease (AD) patients, using retrospective measures of confidence in
      the accuracy of retrieval responses in an episodic odor recognition memory task.
      Relative confidence accuracy was computed as the difference between confidence
      judgments for correct and incorrect responses. In both AD patients and controls,
      individuals reporting 17 years of education or more had significantly more
      accurate levels of confidence than individuals with 12 years or less. Thus,
      education was a significant predictor of retrospective metamemory accuracy in
      healthy aging and AD. 

PMID- 24131066
TI  - A patient with cupping-related post-inflammatory hyperpigmentation successfully
      treated with a 1,927 nm thulium fiber fractional laser.
AB  - Post-inflammatory hyperpigmentation is a rare complication following cupping
      therapy. We report a case of a 26-year-old woman who presented with hyper
      pigmented skin lesions on her lower back which was persistent for 6 months
      following cupping therapy. The 1,927 nm thulium fiber laser (Fraxel re:store
      Dual, Solta Medical Inc., Hayward, CA) was tested leading to near complete
      resolution within four sessions.

PMID- 24131067
TI  - A dystrophic calcinosis cutis case treated with CO2 laser.
AB  - Calcinosis cutis is the deposition of insoluble calcium salts within cutaneous
      tissue. It may be divided into four major subtypes: dystrophic, metastatic,
      idiopathic, and iatrogenic. The most common subtype is dystrophic calcinosis
      cutis. It can occur as a result of local tissue injury. We herein present a child
      with dystrophic calcinosis cutis developed following trauma and successfully
      treated with CO2 laser.

PMID- 24131068
TI  - Erythema ab igne successfully treated with low fluenced 1,064-nm Q-switched
      Neodymium-Doped Yttrium Aluminum Garnet laser.

PMID- 24131069
TI  - Evaluation of safety and efficacy of the TriFractional RF technology for
      treatment of facial wrinkles.
AB  - INTRODUCTION: Skin resurfacing is an accepted gold standard for the treatment of
      skin laxity, photodamage, and appearance of visible lines and wrinkles. However,
      the relatively significant risk and the long downtime associated with whole area
      resurfacing treatments have led to the introduction of fractional resurfacing
      lasers and radiofrequency (RF) technologies. This study was performed in order to
      evaluate the safety and efficacy of the new TriFractional technology using the 3F
      Applicator (A3F), designed to enable skin resurfacing and treatment of wrinkles
      using fractional RF energy. METHODS: Thirty-two subjects were recruited in two
      sites and were treated with the A3F for the reduction of facial wrinkles and
      followed for 3 months after the last treatment. The safety of using the
      TriFractional system was established by the physicians' assessments and
      observations of adverse events after each treatment. To evaluate treatment
      efficacy, subject's pretreatment and posttreatment digital images were assessed
      and graded by two blinded uninvolved physicians based on Fitzpatrick Wrinkle and
      Elastosis scale. RESULTS: No significant adverse side effects were detected or
      reported. Evaluation of photographs of study subjects at baseline and 3 months
      follow-up by the two blinded physicians, revealed improvement (downgrade of at
      least 1 score according to the Fitzpatrick scale) in 80% and 73% of subjects as
      graded by the two reviewers. Study subjects reported no pain to moderate pain
      during treatment with no need of pain relief medication beyond topical
      anesthesia. The majority of study subjects (83.3%) noted that treatment results
      met their expectations to different extent levels, and most of study subjects
      (70%) indicated that they will recommend the A3F treatment to their friends.
      CONCLUSIONS: The results of this study clearly indicate that the TriFractional
      technology using the 3F applicator provides a safe, tolerable, and effective
      treatment of facial wrinkles.

PMID- 24131070
TI  - Effects of microdermabrasion on skin rejuvenation.
AB  - BACKGROUND: Microdermabrasion is a surface treatment, noninvasive, which uses a
      negative pressure and drives programmable inert microcrystals on the skin,
      causing an exfoliation. OBJECTIVE: The aim of this study was to evaluate the
      effects of application of microdermabrasion in human skin rejuvenation. METHODS:
      Eleven women who were undergoing abdominoplasty were considered. An area of 25
      cm2 in the umbilicus to the right was conditioned with microcrystals of Al2O3 in
      maximum flow, negative pressure of 200 mmHg and total of 8 past, the left side
      being used as control. The number of sessions ranged from one to five, with
      weekly intervals, and timing of sample collection ranged from 0 to 132 days.
      Samples were fixed in 10% formaldehyde in phosphate buffer and were evaluated
      histologically. RESULTS: A mild to marked hyperpigmentation was observed and
      remained for a variable period. Histological findings suggest an improvement in
      the epidermal layer with increased thickness and reestablishing their
      interdigitations in the dermis initially observed an increase in collagen
      synthesis. The analysis showed a late stay of epidermal changes, which did not
      occur in the dermis. CONCLUSION: Under the conditions and parameters used in this
      work, the microdermabrasion had a positive skin structure, showing that a viable
      resource in promoting skin rejuvenation.

PMID- 24131071
TI  - Novel post-treatment care after ablative and fractional CO2 laser resurfacing.
AB  - OBJECTIVE: This study evaluates a topical oxygen emulsion (TOE) to reduce adverse
      effects after skin rejuvenation with a fully ablative CO2 laser alone and in
      combination with a fractional ablative CO2 laser. MATERIALS AND METHODS: Patients
      (n = 100) seeking skin rejuvenation underwent CO2 laser resurfacing. Group A
      patients (n = 34) received a single deep fractional laser treatment followed by
      application of Aquaphor immediately after treatment for 24 h and TOE every 6 h
      for the next 6 days. Group B patients (n = 66) underwent both deep fractional and
      fully ablative laser resurfacing followed by application of TOE every 6 h for 7
      consecutive days. RESULTS: Patients in both groups showed clinical improvement
      and a 7.1% overall incidence of adverse effects which included milia (5.1%
      overall) and hyperpigmentation (3.1% overall). For milia, Group A and Group B
      individual adverse effect rates were 11.8% and 1.5%, respectively; for
      hyperpigmentation, individual rates were 0.0% and 3.1%, respectively. CONCLUSION:
      The elimination of petrolatum products in the post-skin care regimen has
      significantly reduced the incidence of post-procedure complications when compared
      with the use of TOE, resulting in the lowest incidence of complications in fully
      ablative or fractional resurfacing published thus far.

PMID- 24131073
TI  - Clinical Trial Study in the Treatment of Nail Psoriasis with Pulsed Dye Laser.
AB  - Abstract Objective: The treatment options for nail psoriasis have been limited,
      and the management of nail psoriasis has been challenging for physicians. This
      study aimed at evaluating the effect of different pulse durations in the
      treatment of nail psoriasis with the 595-nm PDL to determine the optimal pulse
      duration. Methods: Forty patients with bilateral fingernail psoriasis were
      recruited and completed a 6-month trial. PDL was applied on the proximal and
      lateral nailfolds based on random assignment. Eghity nails were treated with 6
      millisecond pulse duration and 9 J/cm(2) whereas 80 nails were treated with 0.45
      millisecond pulse duration and 6 J/cm(2). Nail Psoriasis Severity Index (NAPSI)
      was used to assess the clinical outcome from pretreatment and posttreatment
      photographs. Results: After 6 months of first treatment, there was a significant
      reduction in overall NAPSI, nail matrix NAPSI, and nail bed NAPSI scores from
      baseline in both groups; however, no significant difference was found between the
      two pulse duration groups. Side effects were mild including transient petechiae
      and hyperpigmentation. Conclusion: Both the longer 6-millisecond and shorter 0.45
      millisecond pulses of PDL (595 nm) have been clinically proven to be effective
      for the treatment of nail matrix and nail bed psoriasis.

PMID- 24131072
TI  - Comparison of fractional, nonablative, 1550-nm laser and 595-nm pulsed dye laser
      for the treatment of facial erythema resulting from acne: a split-face, evaluator
      blinded, randomized pilot study.
AB  - BACKGROUND: Postinflammatory erythema is commonly seen in patients with
      inflammatory acne. There are no reliable treatment guidelines for acne erythema.
      OBJECTIVE: We compared the effect and safety of a nonablative, 1550-nm fractional
      laser and a 595-nm pulsed dye laser (PDL) for the treatment of acne erythema.
      MATERIALS AND METHODS: Twelve Korean patients with acne erythema were enrolled.
      Sides of the face were randomized to receive treatment with a fractional laser or
      a PDL for a total of three treatments at 4-week intervals. The assessment of
      effectiveness was mean change in mexameter scores, investigator's and patients'
      clinical assessments. RESULTS: Statistically significant improvements in baseline
      acne erythema were observed through an improved erythema index on both treated
      sides. But, the improvements from each laser treatment were not significantly
      different. Mean scores of investigator assessments were 3.42 +/- 0.67 in
      fractional laser-treated sites and 3.33 +/- 0.65 in PDL-treated sites. Patients
      assessed their improvement as good or excellent in 91.7% of fractional laser
      treated sites and 75% of PDL-treated sites. CONCLUSION: Both lasers are effective
      and safe modalities for the treatment of acne erythema; however, these data
      suggest better clinical efficacy with the use of a 1550-nm, erbium-glass
      fractional laser.

PMID- 24131074
TI  - Dystrophic calcifications after autologous fat injection on face.
AB  - Autologous fat injection is widely used procedure for various functional and
      aesthetic purposes. However, it could result in many immediate or delayed
      complications including dystrophic calcifications. Almost all of the case reports
      about dystrophic calcification after autologous fat injection were result from
      the iatrogenic tissue trauma of breast augmentation. This is a report of a 30
      year-old patient who developed pathologically proven multiple dystrophic
      calcifications on the face after autologous fat injection.

PMID- 24131075
TI  - Effects of collagen tripeptide supplement on skin properties: a prospective,
      randomized, controlled study.
AB  - BACKGROUND: Experimental and clinical trials have indicated that dietary
      supplements can have beneficial effects on skin health. OBJECTIVE: We
      investigated to evaluate the effect of daily collagen peptide (CP) supplement on
      skin properties. METHODS: Thirty-two healthy volunteers were randomized to
      receive either no supplement (Group A), CP 3 g (Group B), CP 3 g, and vitamin C
      500 mg (Group C), or vitamin C 500 mg (Group D) daily for 12 weeks. Skin
      properties evaluated included hydration, transepidermal water loss (TEWL), and
      elasticity using a corneometer, tewameter, and cutometer, respectively. RESULTS:
      Changes from baseline in the corneometer were statistically significant between
      Groups A and B (p = 0.011) and Groups A and C (p = 0.004). There were
      statistically significant differences in cutometer from baseline between Groups A
      and B (p = 0.005) and Groups A and C (p = 0.015). There was no significant
      difference from baseline in the corneometer and cutometer between Groups B and C.
      The greatest changes in TEWL from baseline were seen in Group B, and the second
      greatest changes were seen in Group C. CONCLUSIONS: Daily CP supplementation may
      improve skin hydration and elasticity, but concomitant intake of low-dose vitamin
      C did not enhance the effect of CP on skin properties.

PMID- 24131076
TI  - Sympathetic ophthalmia in pediatric age group: clinical features and challenges
      in management in a tertiary center in southern India.
AB  - PURPOSE: To study the clinical features and visual outcome of sympathetic
      ophthalmia in pediatric patients attending a tertiary care center. METHODS:
      Retrospective review of patients <=16 years with sympathetic ophthalmia seen
      during the period 2001-2011. RESULTS: During this period, 2511 pediatric patients
      with open globe injuries and 14 patients with sympathetic ophthalmia were seen.
      Six patients developed sympathetic ophthalmia during follow-up here. The
      incidence rate of sympathetic ophthalmia is 0.24% (6/2511, 95% CI:0.05-0.43%).
      The commonest presenting signs were anterior uveitis and exudative detachment.
      All patients were treated with systemic steroids, while 7 patients received
      additional immunosuppressive therapy. Eight patients had a follow-up of more than
      6 months. Mean presenting best-corrected visual acuity (1.25 +/- 1.03 logMAR) in
      the sympathizing eye improved significant following treatment (0.42 +/- 0.80
      logMAR, p = 0.003). CONCLUSIONS: The incidence of sympathetic ophthalmia was
      0.24%. Appropriate immunosuppression can lead to favorable visual outcomes in the
      sympathizing eye.

PMID- 24131077
TI  - Variegate porphyria complicated by systemic AA amyloidosis: a case report.
AB  - We report a Japanese woman with variegate porphyria accompanied by amyloid A (AA)
      amyloidosis. Arthropathy involving multiple joints occurred at 35 years old and
      persisted. C-reactive protein was 4.0 mg/dL, but rheumatoid factor was negative.
      Radiographs did not reveal any loss or narrowing of the joint spaces. Two years
      later, blister formation after sun exposure and reddish urine were first noted.
      At the age of 45 years, she developed abdominal pain, nausea, vomiting and
      seizures. After administration of phenobarbital, reddish urine was noted and
      muscular weakness progressed to atonic quadraparesis. Porphyria attack was
      diagnosed from high urinary levels of ? aminolevulinic acid and porphobilinogen.
      At the age of 47 years, hemodialysis was started. At the age of 49 years,
      progression of her gastrointestinal event resulted in death. Autopsy showed
      massive deposits of AA amyloidosis in various organs, including the kidneys and
      digestive tract. Thus, amyloid deposition may have contributed to both end-stage
      renal failure and her gastrointestinal symptoms. This is the first report about
      the coexistence of porphyria and AA amyloidosis. Chronic inflammation related to
      this patient's seronegative arthropathy, although atypical for porphyria, might
      have contributed to the development of AA amyloidosis.

PMID- 24131078
TI  - Extracorporeal membrane oxygenation with direct axillary artery perfusion.
AB  - Extracorporeal membrane oxygenation can be done through several cannulation
      sites. Axillary artery cannulation is commonly performed through a Dacron graft
      sutured in an end-to-side fashion to the axillary artery. Direct cannulation of
      the axillary artery appears a reliable technique with low rate of complications.
      We report our experience in 16 patients using the direct cannulation technique.

PMID- 24131079
TI  - Impact of an implantable steroid contraceptive (etonogestrel-releasing implant)
      on quality of life and sexual function: a preliminary study.
AB  - The aim of the study was to determine the impact of etonogestrel (ENG)-implant
      used for contraceptive purpose on Quality of life (QoL) and on sexual function
      (FSF) of healthy Italian women. The Female Sexual Function Index (FSFI)
      questionnaire and the Short Form-36 (SF-36) validated questionnaire were
      administered at baseline, 3 and 6 months after insertion of Nexplanon. The
      implant seems to have a positive impact on QoL after the first three months of
      therapy. Users showed an improved general health status and physical role status.
      The implant did not show negative effects on libido and on sexual function. In
      the first three months of treatment, users experienced a temporary reduction of
      vitality, mental health, social functioning and emotional role functioning, which
      seem to disappear after six months of therapy.

PMID- 24131080
TI  - The ageing nursing workforce: a global challenge.

PMID- 24131081
TI  - RN work engagement in generational cohorts: the view from rural US hospitals.
AB  - AIM: To describe staff nurse work engagement, identify predictors by generational
      cohort, present implications for nurse managers and suggest future research.
      BACKGROUND: A global nurse shortage looms. While an adequate supply of nurses is
      needed to ensure access to care, access to quality care may be enhanced by an
      adequate supply of highly engaged nurses-those who are dedicated, energized, and
      absorbed. Nurses have long reported the presence of energy depleting practice
      environments. Nurses practicing in professional practice environments may be more
      engaged. METHODS: A non-experimental survey design was executed. Direct care
      Registered Nurses (n = 747) working in five rural acute care hospitals completed
      questionnaires to assess work engagement (Utrecht Work Engagement Scale-9),
      decisional involvement (Decisional Involvement Scale), relational coordination
      (Relational Coordination Survey) and the nursing practice environment (Practice
      Environment Scale of the Nursing Work Index). Descriptive, correlational and
      regression analyses examined work engagement and predictors by generational
      cohort. RESULTS: With the exception of the absorption component, no statistically
      significant differences in engagement emerged across generational cohorts.
      Predictors of engagement differed by cohort, however across all cohorts,
      professional nursing practice environments predicted nurse work engagement.
      CONCLUSIONS: Professional nursing practice environments are significantly
      associated with nurse work engagement. IMPLICATIONS FOR NURSING MANAGEMENT:
      Enhancing nurse work engagement is a complex challenge. Generational cohorts may
      respond to different strategies to enhance engagement.

PMID- 24131083
TI  - Healthy work environments for the ageing nursing workforce.
AB  - AIM: The aim of this article is to describe the physical challenges that ageing
      nurses experience and the facility design features that can promote healthy work
      environments to motivate nurses to continue working. BACKGROUND: Older nurses are
      working longer and beyond the usual retirement age. They often experience chronic
      fatigue and the usual physical and cognitive changes associated with aging.
      Nursing is a physically demanding profession and many older nurses work in pain
      while providing direct patient care. The literature is replete with studies
      focusing on the organisational factors that retain older nurses, but little
      research addresses design factors that facilitate nurses working longer and more
      safely in direct patient care. EVALUATION: Electronic databases in medicine,
      nursing, psychology, and architecture were searched and evidence-based, non
      evidence-based, and review articles and government and organisational newsletters
      were evaluated. KEY ISSUES: Hospital design can help address the physical work
      challenges that older nurses experience. CONCLUSIONS: Older nurses have a wealth
      of knowledge and expertise, and the design of nursing units can optimize their
      work experience. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse Managers must
      participate in design efforts and advocate designs that support aging nurses.

PMID- 24131082
TI  - Work engagement of older registered nurses: the impact of a caring-based
      intervention.
AB  - AIM: The aim of this evaluation research was to measure the impact of a caring
      based intervention on the level of work engagement in older nurses. BACKGROUND:
      Every effort is needed to retain older nurses at the bedside by assisting them to
      revitalise the internal motivation and self- reward that brought them to nursing.
      METHOD: A mixed method evaluation research approach using both qualitative and
      quantitative measurements was used to determine the impact of a caring-based
      programme on improving the work engagement scores of older Registered Nurses
      (RNs). RESULT: The results of this study suggest that leadership strategies aimed
      at improving work engagement using caring theories have a significant positive
      impact. CONCLUSION: The findings contribute to our understanding of how work
      engagement can be enhanced through building work environments where there is a
      sense of belonging and teamwork, where staff are allowed time to decompress as
      well as build positive work relationships. IMPLICATIONS FOR NURSING MANAGEMENT:
      Nurse Leaders (NLs) bear a responsibility to partner with older Registered Nurses
      (RNs) to build engagement in their work life while enhancing the quality of care.
      Successful leaders will find ways to meet these unique challenges by creating a
      healthy work environment.

PMID- 24131084
TI  - Novel HLA-C*07:314 allele identified by sequence-based typing in a French
      lymphoblastic leukemia patient.

PMID- 24131085
TI  - Healthcare use and prescription patterns associated with adult asthma in Korea:
      analysis of the NHI claims database.
AB  - BACKGROUND: National Health Insurance (NHI) claim records could provide valuable
      data for epidemiological studies of asthma in Korea. The aim of this study is to
      estimate the prevalence of adult asthma and to investigate asthma-related
      healthcare use and prescription patterns in Korea over 5 years. METHODS: National
      Health Insurance claim records from January 1, 2006 to December 31, 2010 were
      analyzed in a retrospective, population-based study. Outcome measures included
      asthma prevalence, healthcare use, and prescription patterns over time, by type
      of hospital, and by medical specialty. Additionally, we assessed differences in
      healthcare use between newly diagnosed and previously diagnosed patients in 2009.
      RESULTS: Over 5 years, the prevalence of asthma among Korean adults increased
      from 4944 to 5707 cases per 100,000 population (from 3760 to 4445 in men and from
      6108 to 6951 in women). Asthma-related outpatient visits decreased from 4.82 +/-
      8.02 to 3.44 +/- 5.50. Approximately 3% of all patients were hospitalized and
      2.4% received asthma-related emergency treatment each year. Pulmonary function
      tests were performed in 10-11% of patients an average of 1.3 times per year.
      Newly diagnosed patients experienced fewer asthma-related hospitalizations (1.78%
      vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously
      diagnosed group. Prescriptions of inhaled corticosteroids-based inhalers were
      maintained with about 20% of average of all types of hospitals. CONCLUSIONS: The
      prevalence of asthma in Korea has increased over a recent 5-year period, and
      asthma is still suboptimally controlled. Public health strategies are needed to
      improve the management of asthma in adults.

PMID- 24131086
TI  - The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter
      Clinic Study.
AB  - PURPOSE: It is well established that diabetic peritoneal dialysis (PD) patients
      have a higher mortality rate than the other PD population. This study was
      designed to determine the overall predictors of survival and compared mortality
      and morbidity between diabetic and non-diabetic Turkish PD patients. METHODS: We
      conducted a multicenter retrospective study with 915 PD patients [217 had
      diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis
      adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis
      episodes and ultrafiltration failure during the follow-up period were recorded.
      RESULTS: DM patients were older and had more co-morbidities than non-DM patients.
      Peritonitis rates were higher in DM patients (one episode per 35.9 patient
      months) compared to non-DM patients (one episode per 41.5 patient months) (p <
      0.001). On Kaplan-Meier analysis, patient survival was significantly lower in DM
      patients with the 2-, 3- and 5-year patient survival rates of 90.8%, 87.8% and
      78.2% in non-diabetics and 80.9%, 70.4% and 61.2% in diabetics, respectively. On
      Cox regression analysis, DM (HR 1.5, p = 0.022), age (HR 1.03, p < 0.001),
      baseline serum albumin (HR 0.39, p < 0.001), heart failure (HR 0.038, p = 0.038),
      peripheral artery disease (HR 1.83, p = 0.025) and amputation (HR 4.1, p = 0.009)
      at baseline were significant predictors of overall mortality. CONCLUSIONS:
      Patient survival is lower in diabetic compared to non-diabetic patients on PD.
      Peritonitis rates were also higher in diabetic PD patients. DM, older age,
      albumin level and cardiovascular co-morbidities are predictors of mortality.

PMID- 24131087
TI  - Impact of de novo donor-specific HLA antibodies detected by Luminex solid-phase
      assay after transplantation in a group of 88 consecutive living-donor renal
      transplantations.
AB  - De novo donor-specific HLA antibodies (DSA) after renal transplantation are known
      to be correlated with poor graft outcome and the development of acute and chronic
      rejection. Currently, data for the influence of de novo DSA in patient cohorts
      including only living-donor renal transplantations (LDRT) are limited. A
      consecutive cohort of 88 LDRT was tested for the occurrence of de novo DSA by
      utilizing the highly sensitive Luminex solid-phase assay for antibody detection.
      Data were analyzed for risk factors for de novo DSA development and correlated
      with acute rejection (AR) and graft function. Patients with de novo DSA [31
      (35%)] showed a trend for inferior graft function [mean creatinine change
      (mg/dL/year) after the first year: 0.15 DSA (+) vs. 0.02 DSA (-) (P = 0.10)] and
      a higher rate of AR episodes, especially in case of de novo DSA of both class I
      and II [6 (55%), (P = 0.05)]. Antibody-mediated rejection (AMR) appeared in five
      patients and was significantly correlated with de novo DSA (P = 0.05). Monitoring
      for de novo DSA after LDRT may help to identify patients at risk of declining
      renal function. Especially patients with simultaneous presence of de novo DSA
      class I and class II are at a high risk to suffer AR episodes.

PMID- 24131089
TI  - Mid-term outcome and angiographic follow-up of endarterectomy of the left
      anterior descending artery in patients undergoing coronary artery bypass surgery.
AB  - BACKGROUND AND AIM: With the advancement of percutaneous coronary interventions
      (PCIs), more patients with diffuse coronary artery disease are referred for
      coronary artery bypass graft (CABG) surgery. The use of coronary endarterectomy
      may be useful in such cases. We reviewed our experience with left anterior
      descending artery endarterectomy as an adjunct to conventional CABG. METHODS:
      Between June 2005 and 2011, 58 consecutive patients underwent left anterior
      descending artery endarterectomy as an adjunct to CABG. These were matched to 58
      cases based on age, gender, and Parsonnet score. All data were collected
      prospectively in a departmental database. Postoperative complications and in
      hospital mortality were analyzed. Survival curves were produced. RESULTS: There
      was one death in the endarterectomy group (1.7%) from liver failure. There was no
      significant difference in postoperative complications (especially perioperative
      myocardial infarction) between the two groups with similar hospital mortality.
      Computed tomography (CT) angiography was performed in 24 patients with
      endarterectomy (41%), which showed 100% patency of the left internal mammary
      artery graft to the left anterior descending artery. Survival and freedom from
      intervention at a mean follow-up of 4.2 years were similar. CONCLUSIONS: In
      patients with diffuse disease, the use of endarterectomy is a safe technique with
      no increase in short-term morbidity or mortality. Mid-term results are similar to
      nonendarterectomized patients. This technique is useful in patients with diffuse
      coronary artery disease.

PMID- 24131088
TI  - Neuroimaging correlates of everyday action in dementia.
AB  - The everyday, functional impairments associated with dementia remain poorly
      understood from a neuropsychological perspective. This study investigated
      relations between brain structure volumes and two measures of everyday action
      caregiver questionnaire and direct assessment-in 57 participants with dementia.
      Results showed that caregiver ratings reflecting more functional impairment were
      strongly associated with smaller volumes of deep white matter. Direct assessment
      of everyday task performance in a subsample revealed relations between unique
      neurological substrates and discrete everyday action error types. Findings
      emphasize differences in functional assessment methods and highlight the role of
      white matter in functional deficits in dementia. 

PMID- 24131091
TI  - Randomized clinical trial of CO2 LASER pinpoint irradiation technique versus
      chemical reconstruction of skin scars (CROSS) in treating ice pick acne scars.
AB  - BACKGROUND: Pinpoint irradiation technique CO2 LASER and Chemical Reconstruction
      Of Skin Scars (CROSS) are effective treatments for atrophic acne scars as
      fractional photothermolysis. OBJECTIVE: This study was designed to prospectively
      compare the use of a pinpoint irradiation technique versus TCA CROSS in treating
      ice pick acne scars. METHODS: Thirty-two patients with ice pick acne scars were
      included in this open, label pilot study. Pinpoint irradiation technique by CO2
      LASER and TCA CROSS were applied for the study and control group, respectively.
      Twenty-eight patients with ice pick acne scars were included in this open, label
      pilot study. They were randomly assigned to two groups: the first group (14
      patients) received pinpoint irradiation by CO2 LASER as a study group, and the
      second group (14 patients) received TCA CROSS as a control group. In both
      treatments, there were four sessions at 3-week interval, and 3 months of follow
      up. RESULTS: There were statistically significant difference in acne scar
      severity index and qualitative scarring grading system in the improvement results
      between the study and control groups (p < 0.05). CONCLUSION: Pinpoint irradiation
      technique by CO2 LASER is safe and more effective than TCA CROSS technique.
      Clinical improvement was achieved in all 14 patients without dramatic adverse
      effects.

PMID- 24131092
TI  - Intense pulsed light in the treatment of telangiectasias: case report of Behcet's
      disease with superficial vascular involvement.
AB  - Behcet's disease (BD) is a chronic systemic inflammatory disorder of unknown
      etiology with variable clinical manifestations. HLA-B51 allele is the most
      strongly associated known genetic factor. The mucocutaneous lesions (oral
      aphthae, genital aphthae, skin lesions such as pseudofolliculitis) constitute the
      hallmark of the disease, but also gastrointestinal, vascular, central nervous
      systems, and others may be involved. We report a case of a young man affected
      with Behcet's disease who presented facial telangiectasias and striae rubra in
      the inner region of his arms and at the level of his hips, as uncommon minor
      superficial vascular manifestations of BD. To manage them we have subjected the
      patient to a cycle of Intense Pulsed Light (IPL) therapy. Our findings showed
      that the use of IPL is a safe and effective treatment for telangiectasias and
      striae rubra, also in the complex clinical condition of Behcet's disease. In
      fact, the treatments were well tolerated, no sign of scarring or
      hyper/hypopigmentation was reported and we obtained a significant improvement of
      the lesions in terms of color and size of them.

PMID- 24131093
TI  - Long-pulsed 532-nm Nd:YAG laser treatment for small acquired melanocytic nevi in
      a single session: an 8-year study on 350 Yemeni patients.
AB  - INTRODUCTION: Current laser treatments for acquired melanocytic nevi are
      unpredictable in terms of efficiency and cause considerable scarring. This study
      aimed to assess the efficacy and safety of the long-pulsed 532-nm Nd:YAG laser
      for removing small acquired melanocytic nevi in Yemeni patients. METHODS AND
      MATERIALS: From January 2004 to 2012, 350 patients (M:F; 41:309) with Fitzpatrick
      skin type IV and 1 or more small acquired melanocytic nevi were included in the
      study. The patients were exposed to the following laser parameters: wavelength,
      532 nm; pulse duration, 20 ms; spot size, 2 mm; fluence, 30-50 j/cm2. Photographs
      were taken on 0, 1, 4, and 12 weeks posttreatment. The follow-up period ranged
      from 12 weeks to 5 years. RESULTS: All nevi were completely removed with good to
      excellent cosmetic results in only one session. Side effects were seen in 30% of
      patients; the majority was temporary and, very mild in intensity, such as
      postinflammatory hyperpigmentation. Atrophic and hypertrophic scars were observed
      in 9.4% and 0.6% of cases, respectively. Recurrence was seen within 2-6 months
      after laser treatment in 25 patients. CONCLUSION: The long-pulsed, 532-nm Nd:YAG
      laser is safe and effective in the removal of small acquired melanocytic nevi in
      Yemeni patients.

PMID- 24131094
TI  - Facial scar treated with an intradermal radiofrequency device.

PMID- 24131095
TI  - A combination trial of intradermal radiofrequency and hyaluronic acid filler for
      the treatment of nasolabial fold wrinkles: a pilot study.
AB  - BACKGROUND: Within the last few years, hyaluronic acid (HA) fillers and
      radiofrequency (RF) devices have shown significant promise for skin rejuvenation.
      But the effects of HA only lasted for a relatively short duration. Therefore, we
      tried a new combination therapy of intradermal RF and HA filler. OBJECTIVE: To
      evaluate the clinical efficacy of combination therapy of intradermal RF and HA
      filler for nasolabial fold (NLF) wrinkle reduction. MATERIALS AND METHODS: Ten
      Korean female volunteers with mild to severe NLFs were enrolled. In the control
      group, five subjects were treated with HA filler alone. In the experimental
      group, the other five subjects were treated with intradermal RF prior to HA
      filler. Efficacy was evaluated based on the change on the Wrinkle Severity Rating
      Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS) from baseline.
      RESULTS: At 12 and 24 weeks after treatment, the experimental group showed
      significantly greater improvement in mean WSRS score compared to the control
      group. And two (40%) of the five patients in the experimental group achieved
      'very much improved' and two (40%) showed 'much improved' at 12 weeks after
      treatment. CONCLUSIONS: Intradermal RF treatment prior to HA filler injection may
      provide synergistic and long-lasting effects for the reduction of NLF wrinkles.

PMID- 24131096
TI  - Periorbital lipogranuloma related to filler migration: a rare complication of
      facial fillers.

PMID- 24131097
TI  - Fractional CO2 lasers for the treatment of atrophic acne scars: a review of the
      literature.
AB  - This review examines the efficacy and safety of fractional CO2 lasers for the
      treatment of atrophic scarring secondary to acne vulgaris. We reviewed 20 papers
      published between 2008 and 2013 that conducted clinical studies using fractional
      CO2 lasers to treat atrophic scarring. We discuss the prevalence and pathogenesis
      of acne scarring, as well as the laser mechanism. The histologic findings are
      included to highlight the ability of these lasers to induce the collagen
      reorganization and formation that improves scar appearance. We considered the
      number of treatments and different laser settings to determine which methods
      achieve optimal outcomes. We noted unique treatment regimens that yielded
      superior results. An overview of adverse effects is included to identify the most
      common ones. We concluded that more studies need to be done using uniform
      treatment parameters and reporting in order to establish which fractional CO2
      laser treatment approaches allow for the greatest scar improvement.

PMID- 24131098
TI  - Dermatosis Papulosa Nigra and 10,600-nm CO2 laser, a good choice.
AB  - Dermatosis Papulosa Nigra (DPN) is a common skin condition observed in black
      people and considered a benign epithelial tumor, and more specifically, a
      particular topographic form of seborrheic keratosis. We treated five female
      patients affected by DPN with 10,600-nm CO2 laser. We propose the 10,600-nm CO2
      laser as a valid therapeutic option in patients affected by DPN, since the
      treatment is well tolerated, causes no major side effects, and is effective and
      long lasting.

PMID- 24131099
TI  - Fox Fordyce disease as a secondary effect of laser hair removal.
AB  - Fox Fordyce disease (FFD) has been recently described as an adverse effect of
      laser hair removal. It is an apocrine gland disorder characterized by pruritus
      and a folliculocentric papular eruption in apocrine sweat gland areas. Different
      etiologies have been proposed to be the cause of this entity. It has been
      suggested that a fisical factor could contribute to FFD phatogenesis. We report a
      new case of FFD after laser hair removal.

PMID- 24131100
TI  - The emergence of the 'ethnic donor': the cultural production and relocation of
      organ donation in the UK.
AB  - Organ donation is constructed in the UK as a public responsibility, but more
      particularly as an obligation for members of minority ethnic communities. This
      paper draws attention to the ways in which 'ethnicity' has been made problematic
      by the allocation practices of transplant medicine, health promotion discourses
      and policy developments. Taken together, they have served to culturalise and
      racialise the procurement of organs. As the problem of organ donation is as much
      made inside medicine as outside it, this paper argues greater attention ought to
      be paid to these institutional practices and processes. Drawing on ethnographic
      work in the north of England, and with a specific focus on the organ consent
      encounter, this paper shows how categories of ethnicity in organ transplantation
      are an outcome of biopolitical and institutional practices. It argues that organ
      donation is best thought of, less as a discrete temporally-bounded act of
      decision-making, and more as a set of variegated situated practices that, in all
      manner of ways, problematically produce the publics that transplant medicine has
      come to rely upon so profoundly. 

PMID- 24131101
TI  - Nanoparticles in porous microparticles prepared by supercritical infusion and
      pressure quench technology for sustained delivery of bevacizumab.
AB  - Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for
      sustained delivery of protein drugs, was developed using supercritical infusion
      and pressure quench technology, which does not expose proteins to organic
      solvents or sonication. The delivery system design is based on the ability of
      supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid
      (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to
      bevacizumab, a protein drug administered once a month intravitreally to treat wet
      age related macular degeneration. Bevacizumab coated PLA nanoparticles were
      encapsulated into porosifying PLGA microparticles by exposing the mixture to SC
      CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9
      fold. Confocal and scanning electron microscopy studies demonstrated the
      expansion and porosification of PLGA microparticles and infusion of PLA
      nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from
      NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence
      spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies
      indicated that the released bevacizumab maintained its monomeric form,
      conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP
      was evaluated using noninvasive fluorophotometry after intravitreal
      administration of Alexa Fluor 488 conjugated bevacizumab in either solution or
      NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab
      solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from
      NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained
      release system for protein drugs to reduce frequency of protein injections in the
      therapy of back of the eye diseases. 

PMID- 24131102
TI  - Toward an evolutionary definition of cheating.
AB  - The term "cheating" is used in the evolutionary and ecological literature to
      describe a wide range of exploitative or deceitful traits. Although many find
      this a useful short hand, others have suggested that it implies cognitive intent
      in a misleading way, and is used inconsistently. We provide a formal
      justification of the use of the term "cheat" from the perspective of an
      individual as a maximizing agent. We provide a definition for cheating that can
      be applied widely, and show that cheats can be broadly classified on the basis of
      four distinctions: (i) whether cooperation is an option; (ii) whether deception
      is involved; (iii) whether members of the same or different species are cheated;
      and (iv) whether the cheat is facultative or obligate. Our formal definition and
      classification provide a framework that allow us to resolve and clarify a number
      of issues, regarding the detection and evolutionary consequences of cheating, as
      well as illuminating common principles and similarities in the underlying
      selection pressures. 

PMID- 24131103
TI  - Subretinal fibrosis and uveitis: a spectral domain OCT study of its evolution and
      the minimal therapeutic effect of the off-label treatment with ranibizumab.
AB  - PURPOSE: The subretinal fibrosis and uveitis (SFU) syndrome is a rare multifocal
      posterior uveitis characterized by progressive subretinal fibrosis and
      significant visual loss. METHODS: Slit-lamp examination, dilated fundoscopy,
      fluorescein angiography, Spectral Domain-Optical Coherence Tomography (SD-OCT)
      and laboratory testing were employed. RESULTS: A 52-year-old male presented with
      bilateral (best-corrected visual acuity: 2/10) visual loss. Clinical examination
      revealed bilateral anterior uveitis with posterior synechiae and posterior
      uveitis. Medical workup revealed no pathologic findings. Treatment included 1 gr
      intravenous prednisone followed by oral prednisone, immunosuppresive therapy and
      three ranibizumab injections in the right eye with no improvement. One year
      later, there was significant subretinal fibrosis. In the second year follow-up,
      the picture was slightly worse, with persisting bilateral macular edema and
      fibrosis. CONCLUSIONS: This is the first SFU syndrome report monitored with SD
      OCT. This novel imaging modality can localize the lesion level, guide the
      therapeutic approach and may prove helpful in assessing disease prognosis.

PMID- 24131104
TI  - The versatile nature of the 6-aminoquinolone scaffold: identification of
      submicromolar hepatitis C virus NS5B inhibitors.
AB  - We have previously reported that the 6-aminoquinolone chemotype is a privileged
      scaffold to obtain antibacterial and antiviral agents. Herein we describe the
      design, synthesis, and enzymatic and cellular characterization of new 6
      aminoquinolone derivatives as potent inhibitors of NS5B polymerase, an attractive
      and viable therapeutic target to develop safe anti-HCV agents. The 6-amino-7-[4
      (2-pyridinyl)-1-piperazinyl]quinolone derivative 8 proved to be the best compound
      of this series, exhibiting an IC50 value of 0.069 MUM against NS5B polymerase and
      selective antiviral effect (EC50 = 3.03 MUM) coupled with the absence of any
      cytostatic effect (CC50 > 163 MUM; SI > 54) in Huh 9-13 cells carrying a HCV
      genotype 1b, as measured by MTS assay. These results indicate that the 6
      aminoquinolone scaffold is worthy of further investigation in the context of NS5B
      targeted HCV drug discovery programs. 

PMID- 24131105
TI  - Isolation and characterization of broad spectrum bacteriophages lytic to Vibrio
      harveyi from shrimp farms of Kerala, India.
AB  - Of 33 phages isolated from various shrimp farms in Kerala, India, six were
      segregated to have broad spectrum lytic efficiency towards 87 isolates of Vibrio
      harveyi with cross-infecting potential to a few other important aquaculture
      pathogens. They were further tested on beneficial aquaculture micro-organisms
      such as probiotics and nitrifying bacterial consortia and proved to be
      noninfective. Morphological characterization by transmission electron microscopy
      (TEM) and molecular characterization by RAPD and SDS-PAGE proved them distinct
      and positioned under Caudovirales belonging to Myoviridae and Siphoviridae.
      SIGNIFICANCE AND IMPACT OF THE STUDY: In sustainable aquaculture, application of
      antibiotics is prohibited to manage vibriosis, including the one caused by Vibrio
      harveyi. In lieu of antibiotics, an eco-friendly alternative method, phage
      therapy, is recommended here. To facilitate the same, a set of six broad spectrum
      V. harveyi phages, as cocktail, has been constituted and characterized based on
      morphological traits and by employing molecular tools. These phages were also
      found to infect other aquaculture pathogens belonging to Vibrio and Aeromonas.
      Subsequent to in vivo trials, they can find application in shrimp hatcheries as
      prophylactics and therapeutics.

PMID- 24131106
TI  - Genotype, echocardiography, and survival in familial transthyretin amyloidosis.
AB  - BACKGROUND: More than 100 transthyretin (TTR) variants have been identified which
      cause familial systemic amyloidosis. It has been increasingly recognized that TTR
      variants of familial systemic amyloidosis contribute to clinical characteristics,
      including age at diagnosis, cardiac phenotype and survival. METHODS: Two hundred
      and eighty-two patients who underwent genotyping for TTR variants were
      identified. This study focused on 116 patients representing the three most common
      TTR variants; T60A (n = 58), V30M (n = 37) and V122I (n = 21). The remaining
      subjects (n = 61) were distributed amongst 33 different genotypes and excluded
      from analysis. RESULTS: Age at diagnosis was similar by genotype. Septal,
      posterior wall thickness, right ventricular systolic pressure and left
      ventricular mass index were greater and LVEF lower in the V122I subgroup. At mean
      follow up of 3.0 +/- 2.6 years there were 62 deaths. V30M patients had the best
      survival. Survival was similar between V122I and T60A patients. The association
      of genotype with mortality persisted after adjustments for clinical variables.
      CONCLUSIONS: For familial TTR amyloidosis cardiac involvement is frequent and
      mortality high for T60A, V122I and V30M genotypes. Specific genotype predicted
      severity of phenotypic expression as measured by echocardiography and survival.

PMID- 24131107
TI  - Ion mobility spectrometry reveals the mechanism of amyloid formation of Abeta(25
      35) and its modulation by inhibitors at the molecular level: epigallocatechin
      gallate and scyllo-inositol.
AB  - Amyloid cascades leading to peptide beta-sheet fibrils and plaques are central to
      many important diseases. Recently, intermediate assemblies of these cascades were
      identified as the toxic agents that interact with the cellular machinery. The
      relationship between the transformation from natively unstructured assembly to
      the beta-sheet oligomers to disease is important in understanding disease onset
      and the development of therapeutic agents. Research on this early oligomeric
      region has largely been unsuccessful since traditional techniques measure only
      ensemble average oligomer properties. Here, ion mobility methods are utilized to
      deduce the modulation of peptide self-assembly pathways in the amyloid-beta
      protein fragment Abeta(25-35) by two amyloid inhibitors (epigallocatechin gallate
      and scyllo-inositol) that are currently in clinical trials for Alzheimer's
      Disease. We provide evidence that suppression of beta-extended oligomers from the
      onset of the conversion into beta-oligomer conformations is essential for
      effective attenuation of beta-structured amyloid oligomeric species often
      associated with oligomer toxicity. Furthermore, we demonstrate the ease with
      which ion mobility spectrometry-mass spectrometry can guide the development of
      therapeutic agents and drug evaluation by providing molecular level insight into
      the amyloid formation process and its modulation by small molecule assembly
      modulators. 

PMID- 24131108
TI  - Three-dimensional structure of the Rhodobacter sphaeroides RC-LH1-PufX complex:
      dimerization and quinone channels promoted by PufX.
AB  - Reaction center-light harvesting 1 (RC-LH1) complexes are the fundamental units
      of bacterial photosynthesis, which use solar energy to power the reduction of
      quinone to quinol prior to the formation of the proton gradient that drives ATP
      synthesis. The dimeric RC-LH1-PufX complex of Rhodobacter sphaeroides is composed
      of 64 polypeptides and 128 cofactors, including 56 LH1 bacteriochlorophyll a
      (BChl a) molecules that surround and donate energy to the two RCs. The 3D
      structure was determined to 8 A by X-ray crystallography, and a model was built
      with constraints provided by electron microscopy (EM), nuclear magnetic resonance
      (NMR), mass spectrometry (MS), and site-directed mutagenesis. Each half of the
      dimer complex consists of a RC surrounded by an array of 14 LH1 alphabeta
      subunits, with two BChls sandwiched between each alphabeta pair of transmembrane
      helices. The N- and C-terminal extrinsic domains of PufX promote dimerization by
      interacting with the corresponding domains of an LH1 beta polypeptide from the
      other half of the RC-LH1-PufX complex. Close contacts between PufX, an LH1
      alphabeta subunit, and the cytoplasmic domain of the RC-H subunit prevent the LH1
      complex from encircling the RC and create a channel connecting the RC QB site to
      an opening in the LH1 ring, allowing Q/QH2 exchange with the external quinone
      pool. We also identified a channel that connects the two halves of the dimer,
      potentially forming a long-range pathway for quinone migration along rows of RC
      LH1-PufX complexes in the membrane. The structure of the RC-LH1-PufX complex
      explains the crucial role played by PufX in dimer formation, and it shows how
      quinone traffic traverses the LH1 complex as it shuttles between the RC and the
      cytochrome bc1 complex.

PMID- 24131109
TI  - Neuroprotective effects of ebselen in traumatic brain injury model: involvement
      of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.
AB  - Previous investigations have found that ebselen is able to treat
      neurodegenerative diseases caused by radical and acute total cerebral ischaemia.
      The aim of the present study was to investigate the neuroprotective effects of
      ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were
      randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an
      injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a
      moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg)
      ebselen-treated group. The TBI model was created according using a modified
      weight-drop model. Neurological severity score (NSS), brain water content and
      histopathological deficits were assessed as parameters of injury severity.
      Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like
      receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase
      (MAPK) were examined by chemical colorimetry, quantitative polymerase chain
      reaction and western blotting 24 h after intragastric ebselen administration.
      Rats in the TBI model group exhibited markedly more severe neurological injury
      (higher NSS, more brain water content and more histopathological deficits) than
      those in the sham-operated group. Ebselen treatment significantly ameliorated the
      neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen
      significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38
      MAPK expression, indicating the involvement of NO and p38 MAPK signalling
      pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen
      ameliorated neurological injury, possibly by reducing NO levels and modulating
      the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have
      potential to treat secondary injuries of TBI.

PMID- 24131110
TI  - Will this be a life worth living.

PMID- 24131111
TI  - Exercise in children with common congenital heart lesions: balancing benefits
      with risks.
AB  - Children with corrected common congenital heart lesions are often withheld from
      regular exercise by their parents. While there are some modest risks with
      exercise, they should be seen in perspective, and the life-long benefits of
      regular exercise on general health, mood and well-being should be emphasised. 

PMID- 24131112
TI  - Managing snoring and obstructive sleep apnoea in childhood.
AB  - Snoring assessment and its differentiation from obstructive sleep apnoea are
      difficult based upon a parent history and physical examination of the size of the
      tonsils. Not only is the presence of obstructive sleep apnoea important to
      diagnose, but confirming its severity is the key determinant in prioritising
      treatment in a resource-limited setting. This review provides current knowledge
      on the utility of common diagnostic tests, results of treatment options available
      and implications of treatment and unrecognised or untreated obstructive sleep
      apnoea. 

PMID- 24131113
TI  - Spinal muscular atrophy type I: do the benefits of ventilation compensate for its
      burdens?
AB  - We report the progress of an 8-year-old child with spinal muscular atrophy (SMA)
      type 1. The parents elected in infancy that the child should be on long-term
      ventilation, but all attempts to establish this care at home have failed, so the
      child remains ventilated in the hospital. The leader of the long-term ventilation
      team reports on the child's progress and describes a week in the child's life.
      Two paediatricians argue that the benefits of long-term ventilation have not and
      do not compensate the child for the burdens imposed on her by this treatment and
      explain why they would not support the withdrawal of long-term ventilation now.
      They argue that long-term ventilation might have been avoided by applying to a
      court of law when the child was an infant. An ethicist discusses ethical aspects
      of decision-making in SMA type 1. 

PMID- 24131114
TI  - Should long-term ventilation be offered in severe spinal muscular atrophy.

PMID- 24131116
TI  - Lumbosacral skin-coloured plaque.

PMID- 24131121
TI  - Ethical issues in hypoplastic left heart syndrome.

PMID- 24131122
TI  - Letter to the editor: The author declares that he 'has done consultancy work for
      Nutricia and Wyeth Nutrition, Australia'.

PMID- 24131123
TI  - Re: Conflicts of interest.

PMID- 24131124
TI  - Conflict of interest: editor's commentary.

PMID- 24131126
TI  - Duodenal bulb biopsy for the diagnosis of coeliac disease.

PMID- 24131127
TI  - Primary vesicoureteric reflux grade I to V: no compelling evidence for routine
      antibiotics or surgical intervention.

PMID- 24131128
TI  - ICl-mediated intramolecular twofold iodoarylation of diynes and diynyl diethers
      and amines: synthesis of bis(2H-hydronaphthalene and chromene) and 2H-quinoline
      bearing an alkenyl iodide moiety.
AB  - Electrophilic intramolecular twofold iodoarylation was developed from the
      reaction of diynes and diynyl diethers and amines with iodine monochloride under
      mild conditions, which produced bis(2H-hydronaphthalene and chromene) and 2H
      quinoline bearing an alkenyl iodide moiety in good to excellent yields. These
      compounds underwent Pd-catalyzed cross-coupling reactions with arylboronic acid
      and indium tris(arylthiolate) to produce the functionalized styrene derivatives. 

PMID- 24131129
TI  - 31P magic angle spinning NMR study of flux-grown rare-earth element
      orthophosphate (monazite/xenotime) solid solutions: evidence of random cation
      distribution from paramagnetically shifted NMR resonances.
AB  - We present (31)P magic angle spinning nuclear magnetic resonance spectra of flux
      grown solid solutions of La(1-x)Ce(x)PO4 (x between 0.027 and 0.32) having the
      monoclinic monazite structure, and of Y(1-x)M(x)PO4 (M = V(n+), Ce(3+), Nd(3+), x
      between 0.001 and 0.014) having the tetragonal zircon structure. Paramagnetically
      shifted NMR resonances are observed in all samples due to the presence of
      paramagnetic V(n+), Ce(3+), and Nd(3+) in the diamagnetic LaPO4 or YPO4. As a
      first-order observation, the number and relative intensities of these peaks are
      related to the symmetry and structure of the diamagnetic host phase. The presence
      of paramagnetic shifts allows for increased resolution between NMR resonances for
      distinct atomic species which leads to the observation of low intensity peaks
      related to PO4 species having more than one paramagnetic neighbor two or four
      atomic bonds away. Through careful analysis of peak areas and comparison with
      predictions for simple models, it was determined that solid solutions in the
      systems examined here are characterized by complete disorder (random
      distribution) of diamagnetic La(3+) or Y(3+) with the paramagnetic substitutional
      species Ce(3+) and Nd(3+). The increased resolution given by the paramagnetic
      interactions also leads to the observation of splitting of specific resonances in
      the (31)P NMR spectra that may be caused by local, small-scale distortions from
      the substitution of ions having dissimilar ionic radii.

PMID- 24131130
TI  - Concentration-dependent viscosity of binary and ternary mixtures of
      nonassociating proteins: measurement and analysis.
AB  - Using a recently developed automated viscometer (Grupi, A.; Minton, A. P. Anal.
      Chem. 2012, 84, 10732-10736), the dependence of solution viscosity upon the
      concentrations of bovine serum albumin, hen egg ovomucoid, and human fibrinogen
      have been measured individually and in binary and ternary mixtures over a wide
      range of compositions and at total concentrations of up to 300 g/L. The
      concentration dependence of viscosity of all solutions is quantitatively
      described over the entire range of concentrations and compositions by a
      semiempirical equation requiring specification of only two composition
      independent global parameters per protein. 

PMID- 24131131
TI  - Severe worsening of diabetic retinopathy following bariatric surgery.
AB  - Intensive glycemic control results in long-term reduction of diabetic
      retinopathy, although initial short-term worsening of retinopathy is not
      uncommon. The authors report a patient with a history of stable diabetic
      retinopathy who, despite achieving abrupt glycemic control following laparoscopic
      Roux-en-Y gastric bypass surgery, suffered rapid worsening of her retinopathy
      within 1 month of surgery. Hemoglobin A1c levels were 8.8 preoperatively and
      declined to 7.2 at 3.5 months postoperatively. Although visual function in the
      left eye was spared, useful visual acuity was lost in the right eye. Retinal
      evaluation is recommended in all patients with diabetes mellitus who are
      considering bariatric surgery, with close follow-up as warranted.

PMID- 24131132
TI  - Spontaneous resolution of macular edema in Leber's miliary aneurysms.
AB  - The natural history of Leber's miliary aneurysms is described. A patient with
      Leber's miliary aneurysm presented with count fingers visual acuity due to
      significant lipid exudates, intraretinal hemorrhages, and macular edema. Over the
      next 3 months, the macular edema resolved spontaneously and the visual acuity
      improved to 20/20. The dramatic improvement in both macular edema and visual
      acuity highlights the importance of conservative management before pursuing more
      invasive treatments.

PMID- 24131133
TI  - Asthma and exposure to cleaning products - a European Academy of Allergy and
      Clinical Immunology task force consensus statement.
AB  - Professional and domestic cleaning is associated with work-related asthma (WRA).
      This position paper reviews the literature linking exposure to cleaning products
      and the risk of asthma and focuses on prevention. Increased risk of asthma has
      been shown in many epidemiological and surveillance studies, and several case
      reports describe the relationship between exposure to one or more cleaning agents
      and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and
      specific job tasks have been identified as specific causes and/or triggers of
      asthma. Because research conclusions and policy suggestions have remained
      unheeded by manufactures, vendors, and commercial cleaning companies, it is time
      for a multifaceted intervention. Possible preventive measures encompass the
      following: substitution of cleaning sprays, bleach, and ammonia; minimizing the
      use of disinfectants; avoidance of mixing products; use of respiratory protective
      devices; and worker education. Moreover, we suggest the education of unions,
      consumer, and public interest groups to encourage safer products. In addition,
      information activities for the general population with the purpose of improving
      the knowledge of professional and domestic cleaners regarding risks and available
      preventive measures and to promote strict collaboration between scientific
      communities and safety and health agencies are urgently needed. 

PMID- 24131134
TI  - A generic, flexible protocol for preimplantation human leukocyte antigen typing
      alone or in combination with a monogenic disease, for rapid case work-up and
      application.
AB  - Human leukocyte antigen (HLA) typing of in vitro fertilization (IVF) embryos,
      aims to establish a pregnancy that is HLA compatible with an affected sibling who
      requires hematopoietic stem cell transplantation (HSCT). It can be performed with
      or without preimplantation genetic diagnosis (PGD) for exclusion of a single-gene
      disorder (SGD) and it is a multistep, technically challenging procedure at every
      stage. Our purpose was to address the difficulties of genetic analysis by
      developing a fast, reliable and accurate PGD-HLA protocol, to simplify patient
      work-up and PGD application, while providing high flexibility for combination
      with any SGD. Requests included PGD-HLA for beta-thalassemia (beta-thal)/sickle
      cell disease (most common request), Diamond-Blackfan anemia (DBA), chronic
      granulomatous disease (CGD) and preimplantation-HLA typing only. For HLA
      haplotyping, we selected a panel of 26 short tandem repeats (STRs) distributed
      across the entire HLA locus, following PGD guidelines. When required, mutation
      detection was performed by both a direct and indirect approach. To support
      concurrent SGD exclusion and HLA typing, a one-step, single-tube, multiplex
      fluorescent touchdown-polymerase chain reaction (PCR) was optimized. The
      described touchdown-PCR was successfully applied for all PGD-HLA protocols. Eight
      clinical cycles were performed with a diagnosis achieved for 94.7% of amplified
      biopsied blastomeres. Embryo transfer took place in six cycles, with two
      pregnancies achieved and two healthy female infants (from a twin pregnancy) born
      so far. Our protocol enables HLA typing in a single PCR, reducing the risk of
      contamination and the cost, and providing faster results. It requires minimum
      optimization before clinical application, irrespective of the SGD involved,
      decreasing the waiting time from referral to treatment for all PGD-HLA cases.

PMID- 24131135
TI  - Response to Ollinger et al.,: Nighttime procedures are not associated with
      adverse outcomes in kidney transplantation.

PMID- 24131136
TI  - National and regional dose escalation and cost of tumor necrosis factor blocker
      therapy in biologic-naive rheumatoid arthritis patients in US health plans.
AB  - OBJECTIVE: This study examined the proportion and magnitude of dose escalation
      nationally and regionally among rheumatoid arthritis (RA) patients treated with
      TNF-blockers and estimated the costs of TNF-blocker therapy. METHODS: This
      retrospective cohort study used claims data from US commercially-insured adult RA
      patients who initiated adalimumab, etanercept, or infliximab therapy between 2005
      2009. Biologic-naive patients enrolled in the health plan for >=6 months before
      and >=12 months after therapy initiation were followed for 12 months. Dose
      escalation was assessed using three methods: (1) average weekly dose >
      recommended label dose, (2) average ending dispensed dose > maintenance dose, and
      (3) average dose after maintenance dose > maintenance dose. Annual cost of
      therapy included costs for mean dose and drug administration fees. RESULTS:
      Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were
      included. A significantly lower proportion of etanercept-treated patients had
      dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6%
      infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab
      and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose
      methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional
      dose escalation rates and magnitudes of escalation were directionally consistent
      with national rates. Etanercept had the lowest cost per treated RA patient
      ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030). LIMITATIONS:
      Exclusion of patients not on continuous TNF-blocker therapy limits the
      generalizability; however, ~50% of patients were persistent on therapy for 12
      months. The study population comprised RA patients in commercial health plans,
      thus the results may not be generalizable to Medicare or uninsured populations.
      CONCLUSIONS: In this retrospective study, etanercept patients had the lowest
      proportions and magnitudes of dose escalation across all methods compared to
      adalimumab and infliximab patients nationally and regionally. Mean annual cost
      was lowest for etanercept-treated patients.

PMID- 24131137
TI  - A novel full length KIR3DL1*0070103 identified by molecular typing.

PMID- 24131138
TI  - Deep dermatophytosis and inherited CARD9 deficiency.
AB  - BACKGROUND: Deep dermatophytosis is a severe and sometimes life-threatening
      fungal infection caused by dermatophytes. It is characterized by extensive dermal
      and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes
      and, occasionally, the central nervous system. The condition is different from
      common superficial dermatophyte infection and has been reported in patients with
      no known immunodeficiency. Patients are mostly from North African,
      consanguineous, multiplex families, which strongly suggests a mendelian genetic
      cause. METHODS: We studied the clinical features of deep dermatophytosis in 17
      patients with no known immunodeficiency from eight unrelated Tunisian, Algerian,
      and Moroccan families. Because CARD9 (caspase recruitment domain-containing
      protein 9) deficiency has been reported in an Iranian family with invasive fungal
      infections, we also sequenced CARD9 in the patients. RESULTS: Four patients died,
      at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis.
      No other severe infections, fungal or otherwise, were reported in the surviving
      patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian
      patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due
      to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9
      allele. Both alleles are rare deleterious variants. The familial segregation of
      these alleles was consistent with autosomal recessive inheritance and complete
      clinical penetrance. CONCLUSIONS: All the patients with deep dermatophytosis had
      autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an
      important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale
      pour la Recherche and others.).

PMID- 24131139
TI  - Public reporting, consumerism, and patient empowerment.
AB  - Public reporting of health care outcomes is largely ignored by consumers, perhaps
      because it doesn't include concise, comprehensible information on factors such as
      out-of-pocket costs, the effectiveness of a procedure or treatment, and
      applicability to their situation. 

PMID- 24131141
TI  - Salt licks do not increase local densities of the deer ked, Lipoptena cervi, an
      abundant ectoparasite of cervids.
AB  - The deer ked, Lipoptena cervi (Diptera: Hippoboscidae), is a common ectoparasite
      of the moose, Alces alces (Artiodactyla: Cervidae). Salt licks are widely used to
      manipulate moose movements to prevent damage to saplings and traffic accidents.
      They may cause moose to gather in small areas, which could create aggregates of
      deer ked pupae as the parasite is a short-distance flyer and its dispersion
      depends on its hosts. We investigated whether the population density of flying
      deer keds could be influenced by manipulating salt licks and how environmental
      variables affect parasite density. Densities were estimated in 40 experimental
      sites with four treatments (no salt licks, introduced salt licks, removed salt
      licks, permanent salt licks) in September during 2007-2010. Forest edges, mixed
      forests on mineral soil and coniferous forests on peat soil were the habitats
      with high numbers of parasites. The manipulation of salt licks seemed to be
      ineffective in reducing the density of deer keds as the only factor to show
      statistical significance with parasite numbers in the mixed-model analysis was
      year of determination. Annual deer ked densities correlated with the abundance of
      moose in the region. Moreover, high spring and summer temperatures seemed to
      increase the numbers of flying imagos. 

PMID- 24131140
TI  - Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.
AB  - BACKGROUND: In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel)
      plus gemcitabine, substantial clinical activity was noted in patients with
      advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and
      safety of the combination versus gemcitabine monotherapy in patients with
      metastatic pancreatic cancer. METHODS: We randomly assigned patients with a
      Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with
      higher scores indicating better performance status) to nab-paclitaxel (125 mg per
      square meter of body-surface area) followed by gemcitabine (1000 mg per square
      meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per
      square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15
      every 4 weeks (cycle 2 and subsequent cycles). Patients received the study
      treatment until disease progression. The primary end point was overall survival;
      secondary end points were progression-free survival and overall response rate.
      RESULTS: A total of 861 patients were randomly assigned to nab-paclitaxel plus
      gemcitabine (431 patients) or gemcitabine (430). The median overall survival was
      8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in
      the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval
      [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel
      gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4%
      at 2 years. The median progression-free survival was 5.5 months in the nab
      paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine
      group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82;
      P<0.001); the response rate according to independent review was 23% versus 7% in
      the two groups (P<0.001). The most common adverse events of grade 3 or higher
      were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the
      gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile
      neutropenia occurred in 3% versus 1% of the patients in the two groups. In the
      nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to
      grade 1 or lower in a median of 29 days. CONCLUSIONS: In patients with metastatic
      pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved
      overall survival, progression-free survival, and response rate, but rates of
      peripheral neuropathy and myelosuppression were increased. (Funded by Celgene;
      ClinicalTrials.gov number, NCT00844649.).

PMID- 24131142
TI  - Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory
      signaling.
AB  - B cells detect foreign antigens through their B cell antigen receptor (BCR). The
      BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with
      signaling is endocytosis of the BCR complex, which acts to downregulate signaling
      and facilitate uptake of antigen for processing and display on the cell surface.
      The relationship between signaling and BCR endocytosis is poorly defined. Here,
      we explore the interplay between BCR endocytosis and antigens that either promote
      or inhibit B cell activation. Specifically, synthetic antigens were generated
      that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22.
      The lectin CD22, a member of the Siglec family, binds sialic acid-containing
      glycoconjugates found on host tissues, inhibiting BCR signaling to prevent
      erroneous B cell activation. At low concentrations, antigens that can cocluster
      the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis
      occurs with antigens that bind only the BCR. At higher antigen concentrations,
      rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory
      antigens. Endocytosis of the BCR, in response to synthetic antigens, results in
      its entry into early endocytic compartments. Although the CD22-binding antigens
      fail to activate key regulators of antigen presentation (e.g., Syk), they also
      promote BCR endocytosis, indicating that inhibitory antigens can be internalized.
      Together, our observations support a functional role for BCR endocytosis in
      downregulating BCR signaling. The reduction of cell surface BCR levels in the
      absence of B cell activation should raise the threshold for BCR subsequent
      activation. The ability of the activating synthetic antigens to trigger both
      signaling and entry of the BCR into early endosomes suggests strategies for
      targeted antigen delivery. 

PMID- 24131144
TI  - What are the causes of the ill effects of chronic hemodialysis? The fallacy of
      low interdialytic weight gain and low ultrafiltration rate: lower is not always
      better.

PMID- 24131143
TI  - PTH promotes allograft integration in a calvarial bone defect.
AB  - Allografts may be useful in craniofacial bone repair, although they often fail to
      integrate with the host bone. We hypothesized that intermittent administration of
      parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and
      differentiation, resulting in allograft osseointegration in cranial membranous
      bones. Calvarial bone defects were created in transgenic mice, in which
      luciferase is expressed under the control of the osteocalcin promoter. The mice
      were given implants of allografts with or without daily PTH treatment.
      Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor
      differentiation at the implantation site. Bone formation was evaluated with the
      aid of fluorescence imaging (FLI) and microcomputed tomography (MUCT) as well as
      histological analyses. Reverse transcription polymerase chain reaction (RT-PCR)
      was performed to evaluate the expression of key osteogenic and angiogenic genes.
      Osteoprogenitor differentiation, as detected by BLI, in mice treated with an
      allograft implant and PTH was over 2-fold higher than those in mice treated with
      an allograft implant without PTH. FLI also demonstrated that the bone
      mineralization process in PTH-treated allografts was significantly higher than
      that in untreated allografts. The MUCT scans revealed a significant increase in
      bone formation in allograft + PTH treated mice comparing to allograft + PBS
      treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding
      sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In
      summary, PTH treatment enhances osteoprogenitor differentiation and augments bone
      formation around structural allografts. The precise mechanism is not clear, but
      we show that infiltration pattern of mast cells, associated with the formation of
      fibrotic tissue, in the defect site is significantly affected by the PTH
      treatment. 

PMID- 24131145
TI  - Synthesis of 3,3-disubstituted oxindoles by visible-light-mediated radical
      reactions of aryl diazonium salts with N-arylacrylamides.
AB  - A mild and efficient visible-light-mediated diarylation of N-arylacrylamides with
      aryl diazonium salts under mild conditions has been developed. This method
      provides convenient access to a variety of useful 3,3-disubstituted oxindoles by
      constructing two C-C bonds in one step. 

PMID- 24131146
TI  - X-linked dominant protoporphyria: a new porphyria.
AB  - X-linked dominant protoporphyria (XLDPP) was first reported in the genetics
      literature in 2008. It has a phenotype very similar to erythropoietic
      protoporphyria (EPP), but is distinguished from EPP by higher concentrations of
      erythrocyte protoporphyrin (of which a high proportion is zinc-chelated), its
      apparently higher incidence of liver disease, and an X-linked dominant pattern of
      inheritance. Dermatologists should understand how XLDPP differs from EPP, in
      order to advise newly diagnosed patients correctly about the genetic implications
      and the long-term management strategy. We present a case series of XLDPP to
      introduce this condition to the dermatology literature. 

PMID- 24131147
TI  - Diurnal and menstrual cycles in body temperature are regulated differently: a 28
      day ambulatory study in healthy women with thermal discomfort of cold extremities
      and controls.
AB  - Diurnal cycle variations in body-heat loss and heat production, and their
      resulting core body temperature (CBT), are relatively well investigated; however,
      little is known about their variations across the menstrual cycle under
      ambulatory conditions. The main purpose of this study was to determine whether
      menstrual cycle variations in distal and proximal skin temperatures exhibit
      similar patterns to those of diurnal variations, with lower internal heat
      conductance when CBT is high, i.e. during the luteal phase. Furthermore, we
      tested these relationships in two groups of women, with and without thermal
      discomfort of cold extremities (TDCE). In total, 19 healthy eumenorrheic women
      with regular menstrual cycles (28-32 days), 9 with habitual TDCE (ages 29 +/- 1.5
      year; BMI 20.1 +/- 0.4) and 10 controls without these symptoms (CON: aged 27 +/-
      0.8 year; BMI 22.7 +/- 0.6; p < 0.004 different to TDCE) took part in the study.
      Twenty-eight days continuous ambulatory skin temperature measurements of distal
      (mean of hands and feet) and proximal (mean of sternum and infraclavicular
      regions) skin regions, thighs, and calves were carried out under real-life,
      ambulatory conditions (i-Buttons(r) skin probes, sampling rate: 2.5 min). The
      distal minus proximal skin temperature gradient (DPG) provided a valuable measure
      for heat redistribution from the core to the shell, and, hence, for internal heat
      conduction. Additionally, basal body temperature was measured sublingually
      directly after waking up in bed. Mean diurnal amplitudes in skin temperatures
      increased from proximal to distal skin regions and the 24-h mean values were
      inversely related. TDCE compared to CON showed significantly lower hand skin
      temperatures and DPG during daytime. However, menstrual cycle phase did not
      modify these diurnal patterns, indicating that menstrual and diurnal cycle
      variations in skin temperatures reveal additive effects. Most striking was the
      finding that all measured skin temperatures, together with basal body
      temperature, revealed a similar menstrual cycle variation (independent of BMI),
      with highest and lowest values during the luteal and follicular phases,
      respectively. These findings lead to the conclusion that in contrast to diurnal
      cycle, variations in CBT variation across the menstrual cycle cannot be explained
      by changes in internal heat conduction under ambulatory conditions. Although no
      measurements of metabolic heat production were carried out increased metabolic
      heat generation during the luteal phase seems to be the most plausible
      explanation for similar body temperature increases. 

PMID- 24131148
TI  - Morningness and life satisfaction: further evidence from Spain.
AB  - Life satisfaction is a crucial component of well being, thus research of its
      determinants are of great importance and are conducted worldwide. Recently,
      morningness has been shown to be related to greater life satisfaction in Polish
      and German samples; and in the present study, this relationship was tested in a
      Spanish adult sample. The results provide further evidence for the relationship
      of morningness with higher life satisfaction, which it seems independent of
      culture and geographic location. 

PMID- 24131149
TI  - Morningness-eveningness and sleep patterns of adolescents attending school in two
      rotating shifts.
AB  - School system in which classes are scheduled 1 week in the morning and the other
      in the afternoon, and in which students rotate schedule every week, fosters sleep
      irregularity. In this study, we examined morningness-eveningness of adolescents
      who were involved in such schedule of school time and explored relationship
      between their circadian preferences and sleep characteristics. A large sample of
      2287 students between the ages 11 and 18 years (52% girls) from 24 schools in
      Croatia was studied. The School Sleep Habits Survey was modified to enable
      differentiation of sleep patterns between the two school schedules and weekends.
      Two measures of ME were used: the Morningness-Eveningness Scale for Children
      (MESC) and mid-sleep time on weekends (MSFsc). Both measures showed a shift to
      eveningness starting between the ages 12 and 13 (MESC), or 13 and 14 (MSFsc).
      However, MESC demonstrated a plateau in the shift in older adolescent whereas
      MSFsc indicated further progress of phase delay. Significant differences in sleep
      timing and duration were found between three chronotype groups (Morning,
      Intermediate, and Evening). Generally, Evening types went to bed and woke up the
      latest in all situations. Their sleep duration was the shortest on school week
      with morning schedule. On weekends Morning types slept shorter than other two
      chronotype groups. On school week with afternoon schedule all chronotype groups
      slept close to the recommended 9 h. All three chronotype groups delayed their
      bedtimes and wake-up times, and extended their sleep in situations with fewer
      constraints on sleep timing (i.e. afternoon school schedule, and weekends versus
      morning school schedule). Expectedly, the evening types showed the greatest sleep
      irregularity. The findings of this study suggest that the Croatian school system
      fosters sleep irregularity, but provides more opportunity for fulfilling sleep
      need of all chronotype groups of adolescents. Age effects on morningness
      eveningness observed in Croatian adolescent do not seem to be different from
      those observed in adolescents from other countries involved in a regular morning
      school schedule. Further studies are necessary to explore differences in the
      trend of shift towards eveningness found between the two measures of morningness
      eveningness in this, as well as in other studies. 

PMID- 24131150
TI  - Light at night and melatonin have opposite effects on breast cancer tumors in
      mice assessed by growth rates and global DNA methylation.
AB  - Light-at-night (LAN) is a worldwide problem co-distributed with breast cancer
      prevalence. We hypothesized that exposure to LAN is coincided with a decreased
      melatonin (MLT) secretion level, followed by epigenetic modifications and
      resulted in higher breast cancer tumors growth-rate. Accordingly, we studied the
      effect of LAN exposure and exogenous MLT on breast cancer tumors growth-rate. 4T1
      cells were inoculated into BALB/c short day-acclimated mice, resulting in tumors
      growth. Growth rates were followed under various light exposures and global DNA
      methylations were measured. Results demonstrated the positive effect of LAN on
      tumors growth-rate, reversed by MLT through global DNA methylation. 

PMID- 24131151
TI  - Are all evening-types doomed? Latent class analyses of perceived morningness
      eveningness, sleep and psychosocial functioning among emerging adults.
AB  - An overwhelming amount of research has indicated that evening-types report more
      negative psychosocial functioning as well as more negative sleep characteristics
      (e.g. more sleep problems) relative to morning-types. Researchers also find a
      strong, consistent link between poor sleep characteristics and negative
      psychosocial functioning. These studies, however, have been based on a variable
      centred approach, and thus were not able to assess possible individual
      differences within morning-types and evening-types with respect to their sleep
      characteristics prior to assessing differences in psychosocial functioning. Thus,
      it is not clear whether it is morningness-eveningness per se or sleep
      characteristics that explain the differences in psychosocial functioning found
      between morning-types and evening-types. The purpose of the present two-year
      longitudinal study was to employ a person-centred approach to determine whether
      there are subgroups within morning-types and evening-types based on 10-sleep
      characteristics (e.g. sleep problems and sleep duration). Then subgroups were
      compared on three indices of psychosocial functioning (i.e. academics,
      intrapersonal adjustment and alcohol consumption), both concurrently, as well as
      one year later. Participants were 780 (72.2% female; M = 19.0 years, SD = 0.90)
      emerging adults at a mid-sized university in Southern Ontario, who were either
      morning-types or evening-types. A latent class analysis (LCA) conducted for
      morning-types yielded two subgroups, classified as having good sleep
      characteristics (i.e. morning-good) and poor sleep characteristics (i.e. morning
      poor). Results of a second LCA conducted for evening-types yielded three
      subgroups, classified as having good (i.e. evening-good), moderate (i.e. evening
      moderate) and poor (i.e. evening-poor) sleep characteristics. Results comparing
      subgroups across the 10-sleep characteristics indicated that morning-good and
      evening-good individuals reported very similar scores, and both were
      characterized by the least sleep problems and longest sleep duration relative to
      the other subgroups. In terms of the three psychosocial functioning indices we
      found that academic achievement generally did not differ across the five
      subgroups (i.e. morning-good, morning-poor, evening-good, evening-moderate and
      evening-poor). With respect to intrapersonal adjustment, morning-good and evening
      good subgroups reported significantly better intrapersonal adjustment relative to
      the other subgroups across time. Interestingly, evening-type subgroups generally
      reported higher alcohol consumption than morning-type subgroups. Overall, these
      results suggest that intrapersonal adjustment in particular appears to be
      associated more with differences in sleep characteristics (i.e. sleep problems
      and duration), than with morningness-eveningness per se, while the opposite is
      generally true for alcohol consumption. Lifestyle and personality factors likely
      also play a critical role. Importantly, our study is the first to identify a
      subgroup of evening-types who report good sleep characteristics and similar
      levels of intrapersonal adjustment and academic achievement to that of the
      majority of morning-types. 

PMID- 24131152
TI  - Long-term consistency of diurnal-type preferences among men.
AB  - Diurnal type (chronotype) differentiates individuals on an axis between the
      extremes of evening type to morning type. These diurnal-type preferences are
      thought to be relatively stable, but follow-up studies are sparse. The study aims
      were (1) to compare cross-sectional studies of diurnal type preferences between
      two decades and (2) to analyze the consistency of diurnal-type preferences using
      a longitudinal dataset. We analyzed a total of 18,087 adult males from four
      datasets with information on diurnal type and age. Of these, 2144 were available
      for survival analysis and 567 for analysis of longitudinal diurnal consistency.
      Diurnal type was assessed by asking the individual to what extent they would rate
      themselves a morning or an evening person, categorized into four groups.
      Statistical tests for stability of diurnal type were based on transition matrices
      and p values obtained using likelihood ratios. Cox regression was used to
      calculate the relative risk of all-cause mortality in each of the four diurnal
      type groups. After direct age standardization, 9.5% (95% CI: 9.0-10.1%) of
      participants in the four datasets were evening types. The cross-sectional data
      yielded that morning types were less common in the 2000s than two decades
      earlier. The longitudinal dataset revealed a significant shift from evening type
      to another type from 1985 to 2008 (p = 0.002). The relative risk of all-cause
      mortality was 1.3-fold (95% CI: 1.0-1.6; p = 0.05) higher for evening types
      compared to morning types. At the population level, eveningness appears to have
      become more prevalent over recent decades. However, on the individual level, the
      more morningness the chronotype, the more persistent it remains with aging.

PMID- 24131153
TI  - Evening chronotypes have the increased odds for bronchial asthma and nocturnal
      asthma.
AB  - Earlier studies have found associations of chronotypes with a range of health
      related factors. In the light of these findings, the behavioral trait of
      eveningness in particular associates with determinants that might have a negative
      impact on health. In this study, based on a random sample of population aged 25
      74 years living in five large geographical areas in Finland (N = 6089), we tested
      whether the evening chronotypes have the increased odds for respiratory symptoms
      and diseases. As a result, after controlling for socio-demographic and lifestyle
      factors, evening-types had wheezy breathing without respiratory infection, a
      diagnosed or treated bronchial asthma, awoken in shortness of breath, awoken in
      heavy to breath, wheezy breathing with dyspnea, wheezy breathing as such and
      medication for asthma more often than morning-types (odds ratios (ORs) of 1.5
      1.9) and intermediate-types (ORs of 1.3-1.6). In addition, evening-types had
      current medication for asthma, and awoken in coughing more often (OR = 1.5 and OR
      = 1.4, respectively) than morning-types. Evening-types did not have a diagnosed
      or treated chronic bronchitis more frequently than others. Our results suggest
      that the behavioral trait of eveningness associates with the increased odds for
      the bronchial asthma and nocturnal asthma in particular. 

PMID- 24131154
TI  - Effects of amino acids on melanoma targeting and clearance properties of Tc-99m
      labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone peptides.
AB  - The purpose of this study was to examine the effects of amino acids on melanoma
      targeting and clearance properties of new (99m)Tc-labeled Arg-X-Asp-conjugated
      alpha-melanocyte stimulating hormone (alpha-MSH) peptides. RSD-Lys-(Arg(11))CCMSH
      {c[Arg-Ser-Asp-DTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2},
      RNleD-Lys-(Arg(11))CCMSH, RPheD-Lys-(Arg(11))CCMSH, and RdPheD-Lys-(Arg(11))CCMSH
      peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor
      binding affinities in B16/F1 melanoma cells. The biodistribution of (99m)Tc-RSD
      Lys-(Arg(11))CCMSH, (99m)Tc-RFD-Lys-(Arg(11))CCMSH, and (99m)Tc-RfD-Lys
      (Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The
      substitution of Gly with Ser, Phe, and dPhe increased the MC1 receptor binding
      affinities of the peptides, whereas the substitution of Gly with Nle decreased
      the MC1 receptor binding affinity of the peptide. (99m)Tc-RSD-Lys-(Arg(11))CCMSH
      exhibited the highest melanoma uptake (18.01 +/- 4.22% ID/g) and the lowest
      kidney and liver uptake among these (99m)Tc-peptides. The B16/F1 melanoma lesions
      could be clearly visualized by SPECT/CT using (99m)Tc-RSD-Lys-(Arg(11))CCMSH as
      an imaging probe. It is desirable to reduce the renal uptake of (99m)Tc-RSD-Lys
      (Arg(11))CCMSH to facilitate its potential therapeutic application. 

PMID- 24131155
TI  - Aortic pulse wave velocity is a strong predictor of all--cause and cardiovascular
      mortality in chronic dialysis patients.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate all-cause and
      cardiovascular mortality in chronic hemodialysis patients (CHP) and to identify
      the determinants of mortality predictors. METHODS: In this study with 3 years of
      follow-up period, we studied a cohort of 80 CHPs. Mean age at entry was 59.3 +/-
      11.8 years (duration of dialysis 5.47 +/- 5.16 years). At entry, together with
      standard clinical and biochemical analyses, pulse wave velocity (PWV) was
      determined from time diversity propagation of the common carotid artery and
      common femoral artery flow signals by Doppler ultrasound. RESULTS: The mean PWV
      (m/s) was presented at entry: in survived (12.5 +/- 2.01) and deceased (13.13 +/-
      1.70) patients. The PWV cutoff point (by ROC curves) was 11.8. The regression
      coefficients (b) and Exp (b) hazard ratio coefficients of covariates in Cox
      regression survival analysis in all-cause and CV outcomes was: PWV (b = 0.2617,
      Exp[b] = 1.2992, p = 0.0027; b = 0.3569, Exp[b] = 1.4289, p = 0.0005), CRP (b =
      0.0776, Exp[b] = 1.0807, p = 0.0001; b = 0.0832, Exp[b] = 1.0868, p = 0.0001) and
      albumin (b = -0.1302, Exp[b] = 0.8779, p = 0.0089; b = -0.1881, 0.8285, p =
      0.0030), respectively. Relative risk for exposed groups according to all-cause
      and CV events was 4.2976 (95% CI = 1.6051-11.5071) and 14.3590 (95% CI = 1.6051
      11.5071), p = 0.0037, respectively. CONCLUSIONS: We conclude that PWV, CRP and
      serum albumin are strong independent predictors of overall and CV mortality in
      patients undergoing dialysis.

PMID- 24131156
TI  - Cation-dependent magnetic ordering and room-temperature bistability in azido
      bridged perovskite-type compounds.
AB  - A series of end-to-end azido-bridged perovskite-type compounds [(CH3)nNH4
      n][Mn(N3)3] (n = 1-4) were synthesized and characterized. Structural phase
      transitions indicating the general lattice flexibility were observed and
      confirmed by the crystal structures of different phases. These materials show
      cation-dependent magnetic ordering at up to 92 K and magnetic bistability near
      room temperature. 

PMID- 24131157
TI  - Autoclaving of the middle ear ossicles in an animal experimental model.
AB  - CONCLUSION: Autoclaving the ossicles for 4 min at 134 degrees C impacts
      superficial devitalization and elimination of the squamous epithelium on the
      surface of the ossicles. Bone maintains the integrity, firmness, and lamellar
      structure and ossicles are integrated into the middle ear without any adverse
      reactions. OBJECTIVE: Sixteen guinea pigs were used to explore the effect of
      autoclaving on middle ear ossicles. METHODS: Harvested incudomallear complex was
      autoclaved for 4 min at 134 degrees C and implanted back into the middle ear
      cavity. Exploration of the middle ear was carried out 30 days after implantation.
      Results were compared with a control group of 16 non-autoclaved ossicles.
      RESULTS: Autoclaved ossicles maintained their integrity, firmness, shape, and
      lamellar structure with Haversian systems. Autoclaving substantially decreased
      the vitality of the ossicles. The middle ear mucosa overgrew on the ossicular
      surface. No adverse reactions of soft tissue against ossicles occurred. Although
      the autoclaved ossicles were implanted with tympanic membrane (squamous
      epithelium) the histological examination did not demonstrate any residuum of
      squamous epithelium. In the control group we proved the presence of squamous
      epithelium on the manubrium surface in all cases; all ossicles were vital without
      signs of ostitis.

PMID- 24131158
TI  - Individual mindfulness-based psychotherapy for cannabis or cocaine dependence: a
      pilot feasibility trial.
AB  - BACKGROUND: Mindfulness-based approaches may be effective treatments for
      substance use disorders (SUDs), but they have only been investigated for SUDs in
      the group setting. METHODS: A novel 10-week individual mindfulness-based
      psychotherapy was provided weekly to participants. Tolerability and therapeutic
      feasibility were assessed by retention rates, incidence of adverse events or
      clinical worsening, and abstinence rates at the end of the protocol. RESULTS:
      Twenty-five patients were enrolled overall, and 19 completed (74% overall
      retention rate). Of the 14 cannabis dependent patients enrolled in the study, 11
      completed (79%), and 8 achieved abstinence (57% by intent-to-treat analysis) at
      10 weeks. Of the 11 cocaine dependent patients, 8 completed (73%), and 6 achieved
      abstinence (55% by ITT) at 10 weeks. Abstinence rates were substantially greater
      than those of historical comparison groups. CONCLUSIONS: These findings indicate
      that mindfulness training can be tolerably and feasibly extended to the
      individual psychotherapy setting for the treatment of cocaine or cannabis
      dependence.

PMID- 24131159
TI  - The associations of anticipated parental reactions with smoking initiation and
      progression in adolescents.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to examine whether
      anticipated parental reactions to smoking were related to smoking onset and
      progression during adolescence. METHODS: Data were used from the six-wave, 5-year
      longitudinal "Family and Health" project, in which N = 428 adolescents (M = 13.4,
      SD = .50; 52.3% girls) and their families participated. RESULTS: Parental
      reactions, as anticipated by adolescents, included benign indifference, conflict
      engagement, disclosing disappointment, and positive problem-solving. Findings of
      discrete-time survival analyses indicated no direct association between
      anticipated reactions at baseline and smoking onset within 5 years. However, a
      significant interaction effect was found between parental smoking and anticipated
      parental disappointment. This finding indicates that adolescents of non-smoking
      parents, who expected reactions of annoyance and disappointment, were less at
      risk for initiating smoking than adolescents from smoking parents who expected
      such reactions. None of the anticipated parental reactions were significantly
      related to smoking progression, neither directly nor indirectly. CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: Findings from this study suggest that focusing on
      anticipated reactions to smoking is probably not the most promising endeavor for
      effective smoking prevention and intervention.

PMID- 24131162
TI  - A prospective evaluation of disability associated with alcohol use disorders in
      the United States: an application of the quantile regression approach.
AB  - AIMS: This study aims to estimate, using a unique quantile regression approach,
      the relationship linking alcohol use disorder (AUD) and disability (physical and
      mental) using data from a prospective study of household dwelling adults in the
      United States. METHODS: Data from the two-wave National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC) are used to assess AUD-associated
      disability. A total of 24,716 non-institutionalized adults are grouped into
      "never AUD" and "newly incident AUD" groups. The main outcome variables of
      interest are the changes in physical and mental disability levels between the two
      waves, as measured by summary scores of the Short Form Health Survey Version 2.
      Alcohol use disorder and other mental disorders are assessed by the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule DSM-IV version. Linear
      regression and quantile regression approaches are used for analysis. RESULTS: The
      occurrence of AUD is associated with poorer mental disability outcomes, mainly
      due to the occurrence of alcohol dependence. The association for physical
      disability is dependent on the history of other mental disorders. Among those
      with antecedent mental disorders, alcohol dependence is associated with better
      physical health; among those without antecedent mental disorders, alcohol
      dependence is associated with poorer outcomes in physical health. CONCLUSIONS:
      Evidence tentatively supports a causal link between AUD and mental disability.

PMID- 24131160
TI  - Risky sex in rural America: longitudinal changes in a community-based cohort of
      methamphetamine and cocaine users.
AB  - BACKGROUND AND OBJECTIVES: This study examined the longitudinal associations
      between stimulant use and sexual behaviors. METHODS: Data are from a 3-year
      community-based study of 710 rural stimulant users. Past 30-day crack cocaine,
      powder cocaine, and methamphetamine use and sexual behaviors (any sex,
      inconsistent condom use, and multiple sexual partners) were assessed through in
      person interviews every 6 months. RESULTS: GEE analyses revealed that the odds of
      having sex remained steady over time, with crack cocaine and methamphetamine use
      positively associated with having sex. The odds of multiple sexual partners
      declined, but the odds of inconsistent condom use remained steady over time.
      Crack cocaine use was positively associated with multiple sexual partners,
      whereas powder cocaine use was negatively associated with inconsistent condom
      use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Many rural stimulant users could
      potentially benefit from safe sex educational programs. Such efforts could reduce
      the incidence of HIV and other STIs in rural America.

PMID- 24131161
TI  - Delinquency, aggression, and attention-related problem behaviors differentially
      predict adolescent substance use in individuals diagnosed with ADHD.
AB  - OBJECTIVE: To measure the degree to which childhood and adolescent ratings of
      aggression, attention, and delinquency are related to adolescent substance use
      outcomes in youth diagnosed with attention-deficit/hyperactivity disorder (ADHD).
      BACKGROUND: Childhood externalizing disorders have been shown to predict
      adolescent maladaptive substance use, but few studies have examined the
      differential predictive utility of two distinct dimensions of externalizing
      behavior: aggression and delinquency. METHODS: Ninety-seven clinically referred
      children with ADHD initially took part in this research protocol when they were
      on average 9.05 years of age, and were seen again on average 9.30 years later.
      Participants' parents were administered the Child Behavior Checklist (CBCL) at
      baseline and follow-up, and youth completed the Youth Self Report (YSR) in
      adolescence. At follow-up, substance use severity and diagnosis were assessed
      using semi-structured psychiatric interviews administered separately to parents
      and adolescents. Linear and binary logistic regressions were used to determine
      the association of CBCL- and YSR-rated attention problems, aggression, and
      delinquency to adolescent substance use. RESULTS: Childhood and adolescent
      delinquency, but not aggression, as rated by parents and youths, predicted
      adolescent substance use disorders and substance use severity (all p < .05).
      After accounting for the associations of delinquency and aggression with
      adolescent substance use, ratings of attention problems in childhood and
      adolescence were negatively associated with substance use outcome. CONCLUSIONS:
      Children with ADHD who exhibit high rates of delinquency are at risk for later
      substance use and may require targeted prevention, intervention, and follow-up
      services.

PMID- 24131163
TI  - Prevalence and predictors of injection drug use and risky sexual behaviors among
      adolescents in substance treatment.
AB  - BACKGROUND AND OBJECTIVES: The longitudinal risk for human immunodeficiency virus
      (HIV) infection following adolescent substance treatment is not known. Therefore,
      it is not known if adolescent substance treatment should include HIV prevention
      interventions. To address this important research gap, this study evaluates the
      longitudinal prevalence and predictors of injection drug use (IDU) and sex risk
      behaviors among adolescents in substance treatment. METHODS: Participants were
      260 adolescents (13-18 years) in substance treatment and 201 community control
      adolescents (11-19 years). Participants were assessed at baseline and follow-up
      (mean time between assessments = 6.9 years for the clinical sample and 5.6 years
      for the community control sample). Outcomes included self-report lifetime history
      of IDU, number of lifetime sex partners and frequency of unprotected sexual
      intercourse. RESULTS: At baseline, 7.5% of the clinical sample, compared to 1.0%
      of the community control sample had a lifetime history of IDU (chi12=10.53, p =
      .001). At follow-up, 17.4% of the clinical sample compared to 0% of the community
      control sample had a lifetime history of IDU (chi12=26.61, p = .0005). The number
      of baseline substance use disorders and onset age of marijuana use significantly
      predicted the presence of lifetime IDU at follow-up, after adjusting for baseline
      age, race, and sex. The clinical sample reported more lifetime sex partners and
      more frequent unprotected sex than the community control sample at baseline and
      follow-up. CONCLUSIONS: Many adolescents in substance treatment develop IDU and
      report persistent risky sex. Effective risk reduction interventions for
      adolescents in substance treatment are needed that address both IDU and risky
      sex.

PMID- 24131164
TI  - Treatment outcomes of a combined cognitive behavior therapy and pharmacotherapy
      for a sample of women with and without substance abuse histories on an acute
      psychiatric unit: do therapeutic alliance and motivation matter?
AB  - BACKGROUND AND OBJECTIVES: Women with comorbid psychiatric and substance abuse
      problems (PwSA) experience more consequences from their use and typically have
      the poorest prognosis and outcome, compared to those with psychiatric problems
      but without substance abuse problems (PwoSA). The present study examined outcomes
      of a combined intensive inpatient cognitive behavior therapy (CBT) and
      pharmacotherapy program for women with PwSA and PwoSA. METHODS: Sample consisted
      of 117 women on a women-only acute inpatient unit (PwSA = 50, PwoSA = 67).
      RESULTS: Women in both groups made significant improvements in psychological
      functioning. High motivation at admission and therapeutic alliance at discharge
      were associated with improved psychological functioning at discharge for both
      groups. SCIENTIFIC SIGNIFICANCE: Findings provide preliminary support for the
      efficacy of a combined CBT and pharmacotherapy program for women with psychiatric
      diagnoses on a women-only acute inpatient unit, and for pre-treatment motivation
      and therapeutic alliance as important correlates of better treatment outcomes.

PMID- 24131165
TI  - Clinician beliefs and attitudes about buprenorphine/naloxone diversion.
AB  - BACKGROUND AND OBJECTIVES: Concern about diversion of buprenorphine/naloxone
      (B/N) in the United States may affect prescribing patterns and policy decisions.
      This study examines addiction treatment clinician beliefs and attitudes regarding
      B/N diversion. METHODS: Participants (n = 369) completed a 34-item survey in 2010
      during two national symposia on opioid dependence. We conducted multivariable
      regression, examining the relationship of perceived danger from B/N diversion
      with clinician characteristics and their beliefs about B/N treatment and
      diversion. We compared causal beliefs about diversion among clinicians with and
      without B/N treatment experience. RESULTS: Forty percent of clinicians believed
      that B/N diversion is a dangerous problem. The belief that B/N diversion
      increases accidental overdoses in the community was strongly associated with
      perceived danger from B/N diversion. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:
      Attitudes and beliefs, not education level, were associated with clinician's
      perceived danger from B/N diversion. Clinicians with greater B/N patient
      experience were more likely to believe treatment access barriers are the major
      cause of B/N diversion.

PMID- 24131166
TI  - Depression and substance abuse and dependency in relation to current smoking
      status and frequency of smoking among nondaily and daily smokers.
AB  - BACKGROUND AND OBJECTIVES: Daily smoking rates are decreasing while intermittent
      or nondaily smoking rates are increasing. Little is known about the association
      of depression, alcohol abuse and dependence, and illicit drug abuse and
      dependence with different patterns of smoking, particularly nondaily smoking.
      Thus, we examined these relationships among current smokers versus nonsmokers and
      among those who smoke daily versus less frequently. METHODS: We conducted a
      secondary analysis of 37,897 adults who participated in the 2008 National Survey
      on Drug Use and Health. We developed logistic regression models examining
      predictors of (i) current smoking and (ii) number of days smoking per month (1-10
      days, 11-29 days, and >=30 days) among current smokers, focusing on past-year
      major depression, alcohol abuse and dependence, and illicit drug abuse and
      dependence. RESULTS: Compared to nonsmokers, current smokers more frequently
      reported a major depressive episode (p < .001), alcohol dependence (p < .001) and
      abuse (p < .001), and illicit drug dependence (p < .001) and abuse (p < .001),
      controlling for sociodemographics. Among current smokers, greater smoking
      frequency was associated with illicit drug dependence (p = .004), but lower
      likelihood of alcohol dependence (p = .01), alcohol abuse (p = .01), and illicit
      drug abuse (p = .01). CONCLUSIONS: Although depression and substance use were
      associated with greater likelihood of smoking, most measures were inversely
      associated with frequency of smoking. Thus, it is important to examine underlying
      mechanisms contributing to these counterintuitive findings in order to inform
      intervention approaches. SCIENTIFIC SIGNIFICANCE: With increased rates of
      nondaily smoking, developing a greater understanding about the mental health
      correlates related to this pattern of smoking is critical.

PMID- 24131168
TI  - Acute effects of heroin on emotions in heroin-dependent patients.
AB  - BACKGROUND: Euphoria has been described in heroin-dependent individuals after
      heroin administration. However, affective disturbances and disorders are common
      in heroin dependence. The present study examined the acute effects of heroin on
      emotions in heroin-dependent patients. METHODS: This randomized controlled
      crossover trial included 28 heroin-dependent patients (67.9% male, n = 19) in
      stable heroin-assisted treatment and 20 healthy controls. The patients were
      administered heroin or saline (placebo), the controls were administered saline.
      Data measuring mood, affects and heroin craving (BDI, AMRS, STAI, STAXI, and HCQ)
      were assessed before and 60 minutes after substance injection. RESULTS: Before
      substance injection, heroin-dependent patients showed significantly higher levels
      of anxiety and depression than healthy controls (p < .0001). Heroin
      administration-but not placebo administration-was associated with a significant
      decrease in all negative emotions, including craving, and a significant increase
      in emotional well-being (p < .0001), irrespective of perceived intoxication and
      sedation. After the experiment, the patients did not differ from healthy controls
      in their emotions, once they had received heroin. CONCLUSIONS: Heroin dampens
      craving, negative emotions, and increases positive emotions. These findings
      indicate that heroin regulates emotions and underscore the clinical benefit of
      opioid substitution treatment for heroin-dependent patients.

PMID- 24131167
TI  - A preliminary study on the effect of combined nicotine replacement therapy on
      alcohol responses and alcohol self-administration.
AB  - BACKGROUND AND OBJECTIVES: Limiting alcohol consumption may help prevent alcohol
      mediated smoking relapse in heavy drinking smokers. This pilot study examined
      whether combining a nicotine patch with nicotine nasal spray has stronger
      attenuating effects on alcohol response and consumption than a nicotine patch
      alone. METHODS: Twenty-two non-alcohol dependent heavy drinking smokers completed
      the double-blind cross-over, placebo-controlled study (21 mg nicotine patch +
      nicotine or placebo nasal spray). Six hours after 21 mg nicotine patch
      application, subjective and physiological responses to a priming drink (0.3 g/kg)
      were assessed, followed by two 1-hr alcohol self-administration periods, with
      possible consumption of up to 4 drinks per period (each 0.15 g/kg). Nasal spray
      (1 mg [active] or 0 mg [placebo] per dose) was administered 10 min prior to the
      priming dose and each self-administration period. RESULTS: Active nasal spray did
      not increase serum nicotine levels, compared with placebo administration. The
      number of drinks consumed did not differ by the nasal spray conditions. However,
      positive subjective responses to the priming drink were lower in the active nasal
      spray condition than the placebo nasal spray condition. During the self
      administration period, urge to drink was also lower in the active spray condition
      than the placebo condition. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Augmenting
      the nicotine patch with nicotine nasal spray attenuated positive subjective
      alcohol response and craving and suggests that future studies should investigate
      whether these findings translate to a clinical setting.

PMID- 24131169
TI  - Patterns of substance use initiation among healthcare professionals in recovery.
AB  - BACKGROUND AND OBJECTIVES: Substance-related impairment among healthcare
      professionals has significant public health implications, but little is known
      regarding factors associated with substance use initiation in this group.
      METHODS: In this study, 105 healthcare professionals (80% male), who ranged in
      age from 24 to 68 years (M = 47.1 years, SD = 10.2) completed a self-report
      questionnaire assessing age at first use, education level at first use, means of
      access to substances upon first use, order of substance use initiation, and
      reasons for first and continued substance use. Physicians (51%), pharmacists
      (19.2%), dentists (11.5%), physician assistants (5.8%), and various other allied
      health professionals (12.7%) participated. RESULTS: Results demonstrated that
      73.2% of the professionals used tobacco, 90.4% used alcohol, and 64.4% used other
      drugs before beginning professional school. Reasons for first use of substances
      paralleled those seen in the general public (e.g., curiosity, peer influence,
      availability), and differed from reasons for continued substance use (e.g.,
      getting high, addiction, stress management). CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: Given that onset of substance use among health professionals
      appears to mirror that seen in the general population, their unique treatment
      success rates likely cannot be solely attributed to later age-of-onset of their
      substance use disorder. Delaying experimentation with addictive substances and
      improving efforts at early identification of problematic use are crucial to
      preventing the development of substance use disorders among healthcare
      professionals, as well as the public as a whole.

PMID- 24131171
TI  - Control of phonons in semiconductor nanocrystals via femtosecond pulse chirp
      influenced wavepacket dynamics and polarization.
AB  - The realistic electronic structure of semiconductor nanocrystals is characterized
      by excitonic fine structure and atomistic symmetry breakings that are challenging
      to resolve experimentally. Exciton-phonon coupling is one of the most sensitive
      measures of the excitonic wave functions of the nanocrystals. Here, we exploit
      this sensitivity via chirped pulse and polarization resolved femtosecond
      pump/probe spectroscopy of colloidal CdSe nanocrystals. Pulse chirp measurements
      and simulations are used to explore the contributions of excited- and ground
      state vibrational wavepackets to the observed coherent phonons in the pump/probe
      signals. Polarization resolved pump/probe spectroscopy is used to explore
      electronic and vibrational polarization anisotropies. We find no electronic
      polarization anisotropy, whereas vibrational anisotropy is preserved. 

PMID- 24131170
TI  - Hepatitis C infection in non-treatment-seeking heroin users: the burden of
      cocaine injection.
AB  - BACKGROUND AND OBJECTIVES: In heroin dependent individuals, the HIV epidemic has
      been controlled in countries where access to opioid maintenance treatment (OMT)
      and needle exchange programs (NEP) have been implemented. However, despite
      similar routes of contamination for both viruses, the prevalence of hepatitis C
      (HCV) infection remains high in drug users. The objective of this analysis was to
      identify the prevalence of HCV and the correlates of being HCV-positive in a
      sample of out-of-treatment heroin-dependent individuals. METHODS: Data were
      collected from five inpatient studies (n = 120 participants) conducted at the New
      York State Psychiatric Institute. A logistic regression was used to identify
      correlates of being HCV-positive at baseline. RESULTS: Among the 120 heroin
      dependent volunteers, 42 were HCV-positive. Participants who had heavier alcohol
      use, a longer duration of heroin use, or who reported using heroin by injection
      were more likely to be HCV-positive. Interestingly, participants who had injected
      cocaine during the previous month had a ninefold greater risk of being HCV
      positive compared to non-cocaine users and those who used cocaine by a non
      injecting route. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These findings confirm
      the risk of being HCV-infected through intravenous drug use, especially with
      cocaine use. These results underscore the importance of rethinking interventions
      to prevent HCV infection with combined strategies using pharmacological
      approaches for cocaine dependence and tailored prevention for cocaine users.

PMID- 24131172
TI  - Neutron diffraction studies of the molecular compound [Co2(bta)]n (H4bta =1,2,4,5
      benzenetetracarboxylic acid): in the quest of canted ferromagnetism.
AB  - The exchange mechanism and magnetic structure of the organic-inorganic layered
      molecule-based magnet [Co2(bta)]n (1) (H4bta =1,2,4,5-benzenetetracarboxylic
      acid) have been investigated through variable-temperature magnetic susceptibility
      measurements and supported with a series of neutron diffraction experiments.
      Cryomagnetic studies have shown an antiferromagnetic ordering at a transition
      temperature of 16 K that is followed by the appearance of a weak ferromagnetism
      below 11 K. The weak antiferromagnetic interlayer interaction plays an important
      role in this system in spite of the long interlayer separation. A ferromagnetic
      ordering is induced by applied magnetic fields greater than 1800 G (metamagnetic
      behavior), and a slow magnetic relaxation from this ferromagnetic phase to the
      antiferromagnetic one is observed. The magnetic structure of 1 has been
      elucidated at low temperatures in zero field by neutron powder diffraction
      measurements and was found to be of antiferromagnetic nature with the local
      cobalt(II) spins (magnetic moments) being aligned ferromagnetically in the ac
      plane and antiferromagnetically coupled along the crystallographic b axis. No
      evidence for a long-range spontaneous ferromagnetic component below 11 K was
      observed in the neutron experiment. 

PMID- 24131173
TI  - Structure, dynamics, and interactions of a C4'-oxidized abasic site in DNA: a
      concomitant strand scission reverses affinities.
AB  - Apurinic/apyrimidinic (AP) sites constitute the most frequent form of DNA damage.
      They have proven to produce oxidative interstrand cross-links, but the structural
      mechanism of cross-link formation within a DNA duplex is poorly understood. In
      this work, we study three AP-containing d[GCGCGCXCGCGCG].d[CGCGCGKGCGCGC]
      duplexes, where X = C, A, or G and K denotes an alpha,beta-unsaturated
      ketoaldehyde derived from elimination of a C4'-oxidized AP site featuring a 3'
      single-strand break. We use explicit solvent molecular dynamics simulations,
      complemented by quantum chemical density functional theory calculations on
      isolated X:K pairs. When X = C, the K moiety in the duplex flips around its
      glycosidic bond to form a stable C:K pair in a near-optimal geometry with two
      hydrogen bonds. The X = A duplex shows no stable interaction between K and A,
      which contrasts with AP sites lacking a strand scission that present a
      preferential affinity for adenine. Only one, transient G:K hydrogen bond is
      formed in the X = G duplex, although the isolated G:K pair is the most stable
      one. In the duplex, the stable C:K pair induces unwinding and sharp bending into
      the major groove at the lesion site, while the internal structure of the flanking
      DNA remains unperturbed. Our simulations also unravel transient hydrogen bonding
      between K and the cytosine 5' to the orphan base X = A. Taken together, our
      results provide a mechanistic explanation for the experimentally proven high
      affinity of C:K sites in forming cross-links in DNA duplexes and support
      experimental hints that interstrand cross-links can be formed with a strand
      offset. 

PMID- 24131174
TI  - Plasma IgA antibody levels to malondialdehyde acetaldehyde-adducts are associated
      with inflammatory mediators, obesity and type 2 diabetes.
AB  - AIM: Obesity and type 2 diabetes (T2D) associate with increased oxidative stress.
      Malondialdehyde acetaldehyde (MAA) adducts have been suggested to be one of the
      antigenic epitopes in MDA-LDL responsible for the antibody recognition. Our aim
      was to investigate the associations between plasma IgA antibodies to MAA-LDL,
      inflammatory markers, adipokines, obesity, and T2D. METHODS: IgA to MAA-LDL were
      measured in a subsample (n = 1507) of the Finnish Health 2000 survey. The
      associations between antibody levels, obesity, TNF-alpha, IL-6, high-sensitivity
      (hs) CRP, resistin, adiponectin, fasting plasma (fp) glucose, fp-insulin,
      glycosylated hemoglobin (Hb-A1C), and T2D were investigated. RESULTS: IgA to MAA
      LDL associated positively with fasting plasma insulin. IgA to MAA-LDL were higher
      among subjects with T2D (P < 0.001) compared to subjects with normal glucose
      metabolism. IgA to MAA-LDL associated with obesity, but was not independently (P
      = 0.002, not significant after correction for multiple tests) associated with T2D
      in logistic regression analysis. IgA to MAA-LDL, obesity, and TNF-alpha all
      associated with markers of glucose metabolism. CONCLUSIONS: T2D subjects had
      increased IgA to MAA-LDL compared to subjects with normal glucose metabolism. The
      data suggest that the associations between IgA to MAA-LDL and markers of glucose
      metabolism were independent of TNF-alpha but dependent on components of the
      metabolic syndrome.

PMID- 24131175
TI  - Full disclosure--out-of-pocket costs as side effects.

PMID- 24131176
TI  - The thousand-dollar Pap smear.

PMID- 24131177
TI  - Privacy and all that.

PMID- 24131179
TI  - Images in clinical medicine. Respiratory diphtheria.

PMID- 24131178
TI  - Clinical practice. Calcium supplements and fracture prevention.

PMID- 24131180
TI  - Case records of the Massachusetts General Hospital. Case 32-2013. A 55-year-old
      woman with autoimmune hepatitis, cirrhosis, anorexia, and abdominal pain.

PMID- 24131181
TI  - More than just reassurance on tiotropium safety.

PMID- 24131182
TI  - Angiogenesis in glioblastoma.

PMID- 24131183
TI  - TREM2 and neurodegenerative disease.

PMID- 24131185
TI  - TREM2 and neurodegenerative disease.

PMID- 24131186
TI  - TREM2 and neurodegenerative disease.

PMID- 24131184
TI  - TREM2 and neurodegenerative disease.

PMID- 24131187
TI  - TREM2 and neurodegenerative disease.

PMID- 24131188
TI  - TREM2 and neurodegenerative disease.

PMID- 24131189
TI  - Device surgery without interruption of anticoagulation.

PMID- 24131190
TI  - Device surgery without interruption of anticoagulation.

PMID- 24131191
TI  - Device surgery without interruption of anticoagulation.

PMID- 24131192
TI  - Device surgery without interruption of anticoagulation.

PMID- 24131193
TI  - Metagenomic analysis of tuberculosis--current limitations.

PMID- 24131194
TI  - Spread of Pacific Northwest Vibrio parahaemolyticus strain.

PMID- 24131195
TI  - Images in clinical medicine. Pronator drift.

PMID- 24131196
TI  - Interactive medical case. A curious case of chest pain.

PMID- 24131198
TI  - Small molecule downregulation of PmrAB reverses lipid A modification and breaks
      colistin resistance.
AB  - Infections caused by multi-drug resistant bacteria, particularly Gram-negative
      bacteria, are an ever-increasing problem. While the development of new
      antibiotics remains one option in the fight against bacteria that have become
      resistant to currently available antibiotics, an attractive alternative is the
      development of adjuvant therapeutics that restore the efficacy of existing
      antibiotics. We report a small molecule adjuvant that suppresses colistin
      resistance in multidrug resistant Acinetobacter baumannii and Klebsiella
      pneumoniae by interfering with the expression of a two-component system. The
      compound downregulates the pmrCAB operon and reverses phosphoethanolamine
      modification of lipid A responsible for colistin resistance. Furthermore,
      colistin-susceptible and colistin-resistant bacteria do not evolve resistance to
      combination treatment. This represents the first definitive example of a compound
      that breaks antibiotic resistance by directly modulating two-component system
      activity. 

PMID- 24131197
TI  - Impact of chlorhexidine cleansing of the umbilical cord on cord separation time
      and neonatal mortality in comparison to dry cord care - a nursery-based
      randomized controlled trial.
AB  - AIM: To study the impact of chlorhexidine cleansing of the umbilical cord on cord
      separation time and neonatal mortality in comparison to dry cord care. METHODS:
      This is the secondary analysis of the data of the study which was conducted in
      the NICU of a teaching hospital in north India between 2010 and 2011. Newborns
      (>32 weeks of gestation and weighing >1500 g) were randomized into chlorhexidine
      application and dry cord care groups. Here, we analyze the data regarding time of
      cord separation, umbilical sepsis and mortality in both the groups. RESULTS: One
      hundred and forty (dry care group 70, chlorhexidine group 70) were enrolled and
      finally analyzed. A significant difference was observed among groups in terms of
      time to cord separation (8.92 +/- 2.77 days versus 10.31 +/- 3.23 days; t = 2.20;
      p = 0.02, significant) and neonatal mortality (chi(2) = 4.11; p = 0.042,
      significant). CONCLUSION: Use of chlorhexidine for umbilical cord care shortens
      duration of cord separation and decreases neonatal mortality in NICU. This simple
      intervention can be used as mode for decreasing neonatal mortality.

PMID- 24131199
TI  - Identification of KIR3DL1*0050103 by the sequence-based techniques.

PMID- 24131200
TI  - Impact of organ failure and major complications on outcome in acute Type A aortic
      dissection.
AB  - OBJECTIVES: Organ failure and major complications after operations for acute Type
      A aortic dissection impair outcomes. The objective was to analyze the prevalence
      of organ failure and major complications, their interrelationship and predictors,
      and their impact on early and late survival. DESIGN: All operative survivors 1990
      2009 (n = 335) were retrospectively reviewed. Predictors of organ failure and
      major complications (bleeding, infection, renal or respiratory failure,
      neurological dysfunction, and multisystem organ failure) and their influence on
      in-hospital and long-term mortality were analyzed with multivariable statistical
      methods. RESULTS: Major complication(s) occurred in 153 patients (46%), most
      frequently bleeding and permanent neurological dysfunction (19% each). Increasing
      organ system failure index increased in-hospital mortality markedly: zero (2.9%),
      one (14%), two (33%), three or more (43%), p = 0.002. Reoperation for bleeding
      (odds ratio [95% confidence interval]) 2.6 [1.1-6.3], multisystem organ failure
      4.3 [1.4-13], and permanent neurological dysfunction 14 [6.2-32] were related to
      in-hospital mortality. The latter two and respiratory failure also entailed
      increased long-term mortality. CONCLUSIONS: Organ failure and major complications
      were common and impacted negatively on both in-hospital and long-term survival.
      Strategies to avoid or treat organ failure and major complications should improve
      early and late survival after surgery for acute Type A aortic dissection.

PMID- 24131201
TI  - Carrier state induced by oxytetracycline therapy against streptococcosis in Nile
      tilapia, Oreochromis niloticus (L.).

PMID- 24131202
TI  - Synthesis, pharmacological and structural characterization, and thermodynamic
      aspects of GluA2-positive allosteric modulators with a 3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxide scaffold.
AB  - Positive allosteric modulators of ionotropic glutamate receptors are potential
      compounds for treatment of cognitive disorders, e.g., Alzheimer's disease. The
      modulators bind within the dimer interface of the ligand-binding domain (LBD) and
      stabilize the agonist-bound conformation, thereby slowing receptor
      desensitization and/or deactivation. Here we describe the synthesis and
      pharmacological testing at GluA2 of a new generation of 3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxides. The most potent modulator 3 in complex with GluA2
      LBD-L483Y-N754S was subjected to structural analysis by X-ray crystallography,
      and the thermodynamics of binding was studied by isothermal titration
      calorimetry. Compound 3 binds to GluA2-LBD-L483Y-N754S with a Kd of 0.35 MUM
      (DeltaH = -7.5 kcal/mol and -TDeltaS = -1.3 kcal/mol). This is the first time
      that submicromolar binding affinity has been achieved for this type of positive
      allosteric modulator. The major structural factor increasing the binding affinity
      of 3 seems to be interactions between the cyclopropyl group of 3 and the backbone
      of Phe495 and Met496. 

PMID- 24131203
TI  - Response initiation in young adults at risk for psychosis in the Northern Finland
      1986 Birth Cohort.
AB  - INTRODUCTION: This is one of the very few studies to investigate the specific
      executive function/processing speed component of response initiation in subjects
      at familial risk (FR) for psychosis, and the first such study in subjects at
      clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of
      the general population-based Northern Finland 1986 Birth Cohort in the following
      four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n =
      25) and control subjects (n = 69). The response initiation of these groups was
      compared in three different tests: Semantic fluency, Stockings of Cambridge and
      Spatial working memory. RESULTS: The two risk groups did not differ significantly
      from control group, but differed from, and outperformed the psychosis group in
      semantic fluency response initiation. CONCLUSIONS: Response initiation deficits
      were not evident in a non-help seeking psychosis high-risk sample.

PMID- 24131204
TI  - What are the causes of the ill effects of chronic hemodialysis? Balancing risks:
      blood pressure targets, intradialytic hypotension, and ischemic brain injury.

PMID- 24131205
TI  - Temperature effect on dual fluorescence of 2-(2'-hydroxyphenyl)benzimidazole and
      its nitrogen substituted analogues.
AB  - The effects of temperature on the dual fluorescence of 2-(2'
      hydroxyphenyl)benzimidazole (HPBI) and its nitrogen substituted analogues, viz.,
      2-(2'-hydroxyphenyl)-3H-imidazo[4,5-b]pyridine (HPIP-b) and 2-(2'-hydroxyphenyl)
      1H-imidazo[4,5-c]pyridine (HPIP-c), were investigated in solvents of different
      polarity and hydrogen bonding capability. Absorption, steady-state, and time
      resolved emission spectroscopic techniques were employed for the experimental
      study. Density functional theoretical calculations were performed to find the
      relative population of the conformers. The calculations predict that, with
      increase in temperature, the population of trans-enol increases, while that of
      cis-enol decreases. At all temperatures, the population ratio of cis-enol to
      trans-enol increases in the order HPIP-c < HPIP-b < HPBI. Except for HPBI in
      methanol and ethylene glycol, the fluorescence of both emissions decreases with
      an increase in temperature and is more pronounced in the tautomer band than in
      the normal band. The data are analyzed using the Arrhenius and van't Hoff
      equations. The change in the fluorescence with temperature is governed by (i) the
      change in the relative population of conformers and (ii) the increase in non
      radiative decay from the excited states. The increase in non-radiative decay from
      the normal emission competes with the increase in the relative population of
      trans-enol with a rise in temperature. 

PMID- 24131206
TI  - Aboriginal women's experiences of accessing health care when state apprehension
      of children is being threatened.
AB  - AIMS: To report findings from a study examining the impact of the threat of child
      removal on Aboriginal women's experiences accessing of healthcare services.
      BACKGROUND: A wealth of data highlights the higher proportion of Aboriginal
      children in government care in Canada compared with non-Aboriginal children.
      Aboriginal women experience poorer health outcomes than non-Aboriginal women and
      face significant barriers to healthcare access. However, little is known about
      how these phenomena may intersect. DESIGN: The study was conducted in two phases:
      (1) a secondary analysis of interviews with Aboriginal women and healthcare
      providers (n = 7) that were collected for a larger study; and (2) primary
      interviews with Aboriginal women (n = 9) and healthcare providers (n = 8),
      conducted between July-October 2011. METHODS: Postcolonial feminist perspectives
      and the principles of exploratory, qualitative research guided this ethnographic
      study. Data were analysed using principles of thematic analysis and interpretive
      description. FINDINGS: Aboriginal women whose children are involved with the
      child protection system often experience complex sociopolitical and economic
      challenges, which intersect with the threat of apprehension. Such threat did not
      impact women's decisions to seek healthcare services for their children, but
      experiences of racism, prejudice and discrimination in mainstream healthcare
      agencies and the fear of child apprehension influenced their decisions to access
      health care for themselves in ways that deterred access. CONCLUSION: Racism,
      judgment and discrimination towards Aboriginal mothers in healthcare agencies
      must be addressed. Educating healthcare providers about culturally safe
      approaches to care is critical to mitigating the ongoing impact of colonialism
      and its effects on health of Aboriginal people.

PMID- 24131207
TI  - Unusual C-S bond cleavage in hydro(solvo)thermal reaction that induces two novel
      nickel thiolates: the crown [Ni16(edt)8S9(S2)]4- with an unprecedented 12
      membered ring system and the cagelike [Ni13(edt)8S4(S2)2]2- with two distorted
      cores.
AB  - Complex 1 exhibits the crownlike structure with the unprecedented 12-membered
      ring system, while in 2, a cagelike cluster has been connected with two distorted
      cores in nickel thiolates. The synthesis of novel clusters by way of C-S bond
      cleavage was first reported in the field of nickel thiolates. 

PMID- 24131209
TI  - X-ray attenuation of the liver and kidney in cats considered at varying risk of
      hepatic lipidosis.
AB  - X-ray attenuation of the liver has been measured using computed tomography (CT)
      and reported to decrease in cats with experimentally induced hepatic lipidosis.
      To assess the clinical utility of this technique, medical records and noncontrast
      CT scans of a series of cats were retrospectively reviewed. A total of 112 cats
      met inclusion criteria and were stratified into three hepatic lipidosis risk
      groups. Group 1 cats were considered low-risk based on no history of inappetence
      or weight loss, and normal serum chemistry values; Group 2 cats were considered
      intermediate risk based on weight loss, serum hepatic enzymes above normal
      limits, or reasonably controlled diabetes mellitus; and Group 3 cats were
      considered high risk based on poorly controlled diabetes mellitus due to
      hypersomatotropism. Mean CT attenuation values (Hounsfield units, HU) were
      measured using regions of interest placed within the liver and cranial pole of
      the right kidney. Hepatic and renal attenuation were weakly positively correlated
      with each other (r = 0.2, P = 0.03) and weakly negatively correlated with body
      weight (r = -0.21, P = 0.05, and r = -0.34, P = 0.001, respectively). Mean (SD)
      hepatic and renal cortical attenuation values were 70.7 (8.7) HU and 49.6 (9.2)
      HU for Group 1 cats, 71.4 (7.9) HU and 48.6 (9.1) HU for Group 2, and 68.9 (7.6)
      HU and 47.6 (7.2) HU for Group 3. There were no significant differences in
      hepatic or renal attenuation among groups. Findings indicated that CT measures of
      X-ray attenuation in the liver and kidney may not be accurate predictors of
      naturally occurring hepatic lipidosis in cats. 

PMID- 24131208
TI  - Geometric and electronic structure of the Mn(IV)Fe(III) cofactor in class Ic
      ribonucleotide reductase: correlation to the class Ia binuclear non-heme iron
      enzyme.
AB  - The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct)
      utilizes a Mn/Fe heterobinuclear cofactor, rather than the Fe/Fe cofactor found
      in the beta (R2) subunit of the class Ia enzymes, to react with O2. This reaction
      produces a stable Mn(IV)Fe(III) cofactor that initiates a radical, which
      transfers to the adjacent alpha (R1) subunit and reacts with the substrate. We
      have studied the Mn(IV)Fe(III) cofactor using nuclear resonance vibrational
      spectroscopy (NRVS) and absorption (Abs)/circular dichroism (CD)/magnetic CD
      (MCD)/variable temperature, variable field (VTVH) MCD spectroscopies to obtain
      detailed insight into its geometric/electronic structure and to correlate
      structure with reactivity; NRVS focuses on the Fe(III), whereas MCD reflects the
      spin-allowed transitions mostly on the Mn(IV). We have evaluated 18
      systematically varied structures. Comparison of the simulated NRVS spectra to the
      experimental data shows that the cofactor has one carboxylate bridge, with Mn(IV)
      at the site proximal to Phe127. Abs/CD/MCD/VTVH MCD data exhibit 12 transitions
      that are assigned as d-d and oxo and OH(-) to metal charge-transfer (CT)
      transitions. Assignments are based on MCD/Abs intensity ratios, transition
      energies, polarizations, and derivative-shaped pseudo-A term CT transitions.
      Correlating these results with TD-DFT calculations defines the Mn(IV)Fe(III)
      cofactor as having a MU-oxo, MU-hydroxo core and a terminal hydroxo ligand on the
      Mn(IV). From DFT calculations, the Mn(IV) at site 1 is necessary to tune the
      redox potential to a value similar to that of the tyrosine radical in class Ia
      RNR, and the OH(-) terminal ligand on this Mn(IV) provides a high proton affinity
      that could gate radical translocation to the alpha (R1) subunit. 

PMID- 24131210
TI  - Cloning and expression of a surface immunogenic protein in Streptococcus
      dysgalactiae isolated from fish and its application in enzyme-linked
      immunosorbent assays to diagnose S. dysgalactiae infections in fish.
AB  - Lancefield group C Streptococcus dysgalactiae (GCSD) causes severe necrotic
      lesions in the caudal peduncle in the genus Seriola farmed in Japan. To develop a
      sero-diagnostic method for GCSD infection in farmed fish, we attempted to
      identify a surface immunogenic protein that induces an antibody after infection
      with GCSD by immunoblot analysis using sera collected from infected fish. A
      protein obtained from sodium dodecyl sulfate (SDS) extracts of GCSD was
      identified as S. dysgalactiae surface immunogenic protein (Sd-Sip). Sd-Sip
      exhibited more than 94% homology with a surface antigen or a hypothetical protein
      from S. dysgalactiae mammalian isolates at the nucleotide sequence level.
      Expression of the recombinant Sd-Sip (rSd-Sip) was confirmed by immunoblot
      analysis, that is, its reactivity to GCSD-infected sera. Antibody detection ELISA
      using rSd-Sip and their usefulness for diagnosis of GCSD infection were examined.
      GCSD-infected sera collected from farmed amberjack, Seriola dumerili (Risso),
      showed strong reaction with immobilized rSd-Sip. Meanwhile, sera immunized by
      other pathogenic bacteria of fish were showed ELISA values similar to those of
      non-infected sera. These results of this study suggest that the antibody
      detection ELISA using rSd-Sip is an effective diagnostic method for GCSD
      infection in fish. 

PMID- 24131211
TI  - The bad mother police: theorizing risk orders in the discourses of infant feeding
      practices.
AB  - Modern societies are increasingly concerned with risk, often emphasizing
      individualistic conceptions of risk. However, the construction of risk is social
      and consequential. Risk orders theory interrogates consequences of risk
      discourse, as we struggle to live with our profound desire to avoid threats. This
      article theorizes the construction of three types of risks, collectively termed
      risk orders. First-order risks, those typically studied by risk scholars, are
      constructed claims about concrete threats to a physical body. However,
      constructions of first-order risks prompt additional, abstract risks for
      individuals and collectives. Therefore, we propose that second-order and third
      order risks arise in the shadow of first-order risks. Second-order risks exist
      when we perceive an individual as insufficiently avoiding first-order risks.
      These include threats to our sense of goodness and character, termed moral risks,
      as well as threats to our relationships, termed social risks. Third-order risks
      are threats to collectives' agency and imagination. Human communication produces
      and reproduces a multitude of risks, not simply concrete first-order risks. The
      risks we construct actualize consequential social worlds that deeply affect our
      identity, social relations, and cultural imagination. This article posits risk
      orders theory and applies it to infant feeding discourse. 

PMID- 24131212
TI  - Twenty years' experience at the Heart Transplant Center, Aarhus University
      Hospital, Skejby, Denmark.
AB  - OBJECTIVES: The Heart Transplantation Center, Aarhus University Hospital, Skejby,
      now has 20 years' experience with heart transplantation (HTX). This study aims to
      evaluate long-term outcome after HTX including incidences of cancer and severe
      renal dysfunction. DESIGN: Outcomes were reviewed using the transplant database
      of our department, the Scandiatransplant database, hospital medical records, and
      national database of biopsies. RESULTS: From December 31, 1992 to February 27,
      2013, a total of 258 patients underwent index HTX. Survival for the whole patient
      cohort at 1 month and 1 year was 95% and 88%. Long-term survival estimates of 5,
      10, 15, and 20 years were 80%, 70%, 55%, and 40%, respectively. Median survival
      time was 15.6 years. Significant improvement in survival was observed from the
      1992-1998 vs. 1999-2005 era and the 1992-1998 vs. the 2006-2012 era. Three
      patients (1%) underwent renal transplantation, and 29 patients (11%) developed
      severe renal dysfunction requiring dialysis. Sixty-four (25%) patients developed
      cancer, with skin cancer being most common. CONCLUSION: HTX is an excellent
      treatment for selected patients with end-stage heart failure. The prognosis has
      improved in the latest transplantation eras. With balanced immunosuppressive
      treatment, severe renal dysfunction and cancer can be limited to an acceptable
      level.

PMID- 24131214
TI  - Direct arylations for study of the air-stable P-heterocyclic biradical: from wide
      electronic tuning to characterization of the localized radicalic electrons.
AB  - We have developed methods for installing aryl substituents directly on the
      phosphino groups of the 1,3-diphosphacyclobutane-2,4-diyl system. The aryl
      substituents tuned the electronic and structural characteristics of the biradical
      unit both in solution and in the solid state. 1-tert-butyl-2,4-bis(2,4,6-tri-tert
      butylphenyl)-1,3-diphosphacyclobuten-4-yl anion, prepared from phosphaalkyne
      (Mes*C=P; Mes* = 2,4,6-tBu3C6H2) and t-butyllithium, was allowed to react with an
      electron-deficient N-heterocyclic reagent. The corresponding N-heteroaryl
      substituted P-heterocyclic biradicals were produced via SNAr reactions.
      Biradicals bearing perfluorinated pyridyl substituents exhibited photoabsorption
      properties comparable to those of previously reported derivatives because the
      highest occupied and lowest unoccupied molecular orbit levels were reduced by a
      similar amount. In contrast, the triazine substituent reduced the band gap of the
      biradical unit, and the large red shift in the visible absorption and high
      oxidation potential were further tuned via subsequent SNAr and Negishi coupling
      reactions. The amino-substituted triazine structure provided a strongly electron
      donating biradical chromophore, which produced unique p-type semiconducting
      behavior even though there was no obvious pi-overlap in the crystalline state.
      The single-electron transfer reaction involving Mes*C=P, phenyllithium, and
      iodine afforded 1,3-diphenyl-2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3
      diphosphacyclobutane-2,4-diyl via the intermediate P-heterocyclic monoradical.
      The tetraaryl-substituted symmetric biradical product was used to determine the
      electron density distribution from the X-ray diffraction data. The data show
      highly localized radicalic electrons around the skeletal carbon atoms, moderately
      polarized skeletal P-C bonds in the four-membered ring, and no covalent
      transannular interaction. 

PMID- 24131213
TI  - Functionally and phenotypically distinct subpopulations of marrow stromal cells
      are fibroblast in origin and induce different fates in peripheral blood
      monocytes.
AB  - Marrow stromal cells constitute a heterogeneous population of cells, typically
      isolated after expansion in culture. In vivo, stromal cells often exist in close
      proximity or in direct contact with monocyte-derived macrophages, yet their
      interaction with monocytes is largely unexplored. In this report, isolated
      CD146(+) and CD146(-) stromal cells, as well as immortalized cell lines
      representative of each (designated HS27a and HS5, respectively), were shown by
      global DNase I hypersensitive site mapping and principal coordinate analysis to
      have a lineage association with marrow fibroblasts. Gene expression profiles
      generated for the CD146(+) and CD146(-) cell lines indicate significant
      differences in their respective transcriptomes, which translates into differences
      in secreted factors. Consequently, the conditioned media (CM) from these two
      populations induce different fates in peripheral blood monocytes. Monocytes
      incubated in CD146(+) CM acquire a tissue macrophage phenotype, whereas monocytes
      incubated in CM from CD146(-) cells express markers associated with pre-dendritic
      cells. Importantly, when CD14(+) monocytes are cultured in contact with the
      CD146(+) cells, the combined cell populations, assayed as a unit, show increased
      levels of transcripts associated with organismal development and hematopoietic
      regulation. In contrast, the gene expression profile from cocultures of monocytes
      and CD146(-) cells does not differ from that obtained when monocytes are cultured
      with CD146(-) CM. These in vitro results show that the CD146(+) marrow stromal
      cells together with monocytes increase the expression of genes relevant to
      hematopoietic regulation. In vivo relevance of these data is suggested by
      immunohistochemistry of marrow biopsies showing juxtaposed CD146(+) cells and
      CD68(+) cells associated with these upregulated proteins.

PMID- 24131216
TI  - Asymmetric nasal mucosal thickening in healthy dogs consistent with the nasal
      cycle as demonstrated by MRI and CT.
AB  - The nasal cycle is a physiological phenomenon that causes regular cyclical
      congestion and decongestion of the venous sinusoids lining the nasal mucosa. The
      purpose of this prospective study was to describe magnetic resonance imaging
      (MRI) and computed tomographic (CT) features of the normal nasal cycle in a group
      of dogs. Five dogs were recruited that met the following criteria: 8 to 15 months
      old, nonbrachiocephalic breed, no clinical signs or history of nasal disease, and
      undergoing anesthesia for problems unrelated to the nasal cavity. Nasal MRI (n =
      5) and CT scans (pre- and postcontrast, n = 5) were acquired. Images were
      evaluated subjectively by two board-certified radiologists and objectively by a
      diagnostic imaging intern using regions of interest placed on each side of the
      nasal cavity. Findings were compared using Cohen's kappa coefficient and Students
      t-test on log-transformed data. All dogs showed diffuse unilateral mucosal
      thickening of the rostral part of the nasal cavity in both MRI and CT studies.
      This mucosal thickening shifted sides between examinations in three dogs. Changes
      appeared most marked on T2-weighted scans. No asymmetric mucosal changes were
      seen in the mucosa of the ethmoturbinates, vomer-nasal septum, hard palate or the
      frontal sinuses in any patient on MRI or CT. Computed tomographic contrast
      enhancement of the thickened mucosa was not statistically significant (P-value <
      0.08). In conclusion, the normal nasal cycle may cause asymmetrical mucosal
      changes in the rostral part of the nasal cavity that mimic MRI and CT
      characteristics previously reported for inflammatory disease in dogs. 

PMID- 24131217
TI  - Binding interactions of beta-conglycinin and glycinin with vitamin B12.
AB  - Vitamin B12 deficiency is a problem for many elderly people around the world that
      is caused by food-cobalamin malabsorption syndrome due to gastrointestinal
      problems. In this study, the molecular interactions of VB12 with two major soy
      protein fractions, beta-conglycinin (7S) and glycinin (11S), were studied using
      fluorescence and far-UV circular dichroism spectroscopic techniques. The results
      show that the fluorescence of 7S and 11S was quenched by VB12 through binding
      related quenching after correcting for the inner-filter effect. Both 7S and 11S
      had a good affinity to VB12 as indicated by their high binding constant 1.252 (+/
      0.085) * 10(4) M(-1) for 7S and 0.952 (+/-0.04) * 10(4) M(-1) for 11S at 292 K,
      respectively. Such binding induced a more organized protein confirmation with
      increased beta-sheet and beta-turn structure components and a more folded
      tertiary structure. It is deduced that VB12 was bound in the interior of protein
      three-dimensional network mainly via hydrophobic interactions to form 7S-VB12 and
      11S-VB12 complexes. The results suggest that soy protein has potential to be used
      as carrier of VB12. 

PMID- 24131218
TI  - Metabolically stable dibenzo[b,e]oxepin-11(6H)-ones as highly selective p38 MAP
      kinase inhibitors: optimizing anti-cytokine activity in human whole blood.
AB  - Five series of metabolically stable disubstituted dibenzo[b,e]oxepin-11(6H)-ones
      were synthesized and tested in a p38alpha enzyme assay for their inhibition of
      tumor necrosis factor-alpha (TNF-alpha) release in human whole blood. Compared to
      the monosubstituted dibenzo[b,e]oxepin-11(6H)-one derivatives, it has been shown
      that the additional introduction of hydrophilic residues at position 9 leads to a
      substantial improvement of the inhibitory potency and metabolic stability. Using
      protein X-ray crystallography, the binding mode of the disubstituted
      dibenzoxepinones and the induction of a glyince flip in the hinge region were
      confirmed. The most potent compound of this series, 32e, shows an outstanding
      biological activity on isolated p38alpha, with an IC50 value of 1.6 nM,
      extraordinary selectivity (by a factor >1000, Kinase WholePanelProfiler), and low
      ATP competitiveness. The ability to inhibit the release of TNF-alpha from human
      whole blood was optimized down to an IC50 value of 125 nM. With the promising
      dibenzoxepinone inhibitor 3i, a pharmacokinetic study in mice was conducted. 

PMID- 24131219
TI  - Spontaneous clearance of hepatitis B surface antigenemia after long-term
      hemodialysis.
AB  - Persistent infection with the hepatitis B virus (HBV) [as indicated by chronic
      HBV surface antigenemia (HBsAg)] continues to be an important problem in end
      stage renal disease (ESRD) patients and specifically in those receiving
      maintenance hemodialysis (HD). Patients on HD who are HBsAg-positive for a year
      have little chance of ever eliminating the virus; hence, clearance of HBsAg is a
      rare event in long-term HD patients. We report the case of a 62-year-old diabetic
      woman who was HBsAg-positive at the time she started HD and remained so until 10
      years later when she became HBsAg-negative followed by the development of
      hepatitis B surface antibody (anti-HBs). Prior to her seroconversion, she
      suffered a persistent infection of her HD arteriovenous graft (AVG) that required
      prolonged antibiotics and several surgical procedures. We speculate that this
      immune stimulation contributed to her seroconversion. 

PMID- 24131220
TI  - Heteroscorpionate magnesium alkyls bearing unprecedented apical sigma-C(sp3)-mg
      bonds: heteroselective ring-opening polymerization of rac-lactide.
AB  - The previously described reaction of the low sterically hindered
      heteroscorpionate lithium acetamidinates [Li(kappa(3)-pbpamd)(THF)] and
      [Li(kappa(3)-tbpamd)(THF)] with a series of commercially available Grignard
      reagents RMgCl in an equimolecular ratio yielded the magnesium monoalkyls
      [Mg(R)(kappa(3)-NNN)] (NNN = pbpamd, R = CH2SiMe3, Et (1), Bn (2); NNN = tbpamd,
      R = CH2SiMe3, Et (3), Bn (4)). However, subsequent reaction of these monoalkyls
      [Mg(R)(kappa(3)-NNN)] with two additional equivalents of the same RMgCl in
      tetrahydrofuran gave rise to dinuclear dialkyls of the type [RMg(kappa(3)
      N,N,N;kappa(2)-C,N)MgR(thf)] (kappa(3)-N,N,N;kappa(2)-C,N = pbpamd(-), R =
      CH2SiMe3 (5), Et (6); kappa(3)-N,N,N;kappa(2)-C,N = tbpamd(-), R = CH2SiMe3 (7),
      Et (8)). Furthermore, when the reaction was carried out in a mixture of
      tetrahydrofuran/dioxane with the same stoichiometry, a new family of tetranuclear
      tetraalkyl magnesium complexes [{RMg(kappa(3)-N,N,N;kappa(2)-C,N)MgR}2{MU-O,O
      (C4H8)}] (kappa(3)-N,N,N;kappa(2)-C,N = pbpamd(-), R = CH2SiMe3 (9), Et (10), Bn
      (11); kappa(3)-N,N,N;kappa(2)-C,N = tbpamd(-), R = CH2SiMe3 (12), Et (13), Bn
      (14)) was obtained. In both families, an apical methine C-H activation process on
      the heteroscorpionate takes place. The single-crystal X-ray structures of 4, 8,
      9, and 12 confirm the nuclearity of each family, with 4-coordinative arrangements
      for all magnesium atoms. More importantly, the presence in the di- and
      tetranuclear complexes of unprecedented apical carbanions with a direct sigma
      C(sp(3))-Mg covalent bond, and as a result, the existence of stereogenic
      magnesium centers, have been unambiguously confirmed. Interestingly, the
      dinuclear dialkyls 5 and 7, as well as the tetranuclear tetraalkyls 9, 10, and
      12, can act as highly efficient single-component living initiators for the ring
      opening polymerization of epsilon-caprolactone and lactides. Lactide (LA)
      polymerizations afforded polylactide (PLA) materials with medium molecular
      weights in only a few minutes even at 20  degrees C for L-LA and in a few hours
      at 50  degrees C for rac-LA propagations. More importantly, microstructural
      analysis of the poly(rac-lactide) materials revealed that the tetranuclear tetra
      alkyl 12 exerts enhanced levels of heteroselectivity on the PLAs under mild
      conditions, with Ps values up to 0.78.

PMID- 24131221
TI  - Bayesian experimental design for models with intractable likelihoods.
AB  - In this paper we present a methodology for designing experiments for efficiently
      estimating the parameters of models with computationally intractable likelihoods.
      The approach combines a commonly used methodology for robust experimental design,
      based on Markov chain Monte Carlo sampling, with approximate Bayesian computation
      (ABC) to ensure that no likelihood evaluations are required. The utility function
      considered for precise parameter estimation is based upon the precision of the
      ABC posterior distribution, which we form efficiently via the ABC rejection
      algorithm based on pre-computed model simulations. Our focus is on stochastic
      models and, in particular, we investigate the methodology for Markov process
      models of epidemics and macroparasite population evolution. The macroparasite
      example involves a multivariate process and we assess the loss of information
      from not observing all variables. 

PMID- 24131222
TI  - Young adult women's experiences of body image after bariatric surgery: a
      descriptive phenomenological study.
AB  - AIM: To understand the lived experience of body image in young women after
      obesity surgery. BACKGROUND: Quantitative studies have documented that health
      related quality of life and body image are improved after bariatric surgery,
      probably due to significant weight loss. Female obesity surgery candidates are
      likely to be motivated by dissatisfaction regarding physical appearance. However,
      little is known about the experience of the individual woman, leaving little
      understanding of the association between bariatric surgery and changes in health
      related quality of life and body image. DESIGN: A qualitative descriptive
      phenomenological study. METHODS: Data were collected over 4 months during 2010.
      Selection for interview was carried out through purposeful sampling. The
      participants were five young women who underwent bariatric surgery (range: 1-12
      months). In-depth, semi-structured interviews were analysed by systematic text
      condensation influenced by Giorgi's phenomenological method and supplemented by
      elements from narrative analysis. FINDINGS: The analysis revealed three concepts:
      solution to an unbearable problem, learning new boundaries and hopes of
      normalization. These revelatory concepts were synthesized into one major theme:
      on the edge of control, that is describing these women's feelings of being on the
      edge of balance between control and loss of control. CONCLUSION: Perception of
      control may be an essential aspect of body image and the key to understanding
      these young women's feelings of empowerment and quality of life through body
      control postbariatric surgery. Future studies should focus on how body control is
      an essential aspect of body image, which may contribute to long-term weight loss
      maintenance and improve quality of life.

PMID- 24131223
TI  - Forbearance for fluoxetine: do monoaminergic antidepressants require a number of
      years to reach maximum therapeutic effect in humans?
AB  - It is of high clinical interest to better understand the timecourse through which
      psychiatric drugs produce their beneficial effects. While a rough estimate of the
      time lag between initiating monoaminergic antidepressant therapy and the onset of
      therapeutic effect in depressed subjects is two weeks, much less is known about
      when these drugs reach maximum effect. This paper briefly examines studies that
      directly address this question through long-term antidepressant administration to
      humans, while also putting forth a simple theoretical approach for estimating the
      time required for monoaminergic antidepressants to reach maximum therapeutic
      effect in humans. The theory invokes a comparison between speed of antidepressant
      drug response in humans and in rodents, focusing on the apparently greater speed
      in rodents. The principal argument is one of proportions, comparing earliest
      effects of these drugs in rodents and humans, versus their time to reach maximum
      effect in these organisms. If the proportionality hypothesis is even coarsely
      accurate, then applying these values or to some degree their ranges to the
      hypothesis, may suggest that monoaminergic antidepressants require a number of
      years to reach maximum effect in humans, at least in some individuals. 

PMID- 24131224
TI  - Multiplex blood reporters for simultaneous monitoring of cellular processes.
AB  - Reporters secreted into the conditioned medium of cells in culture or into blood
      in vivo have shown to be useful tools for simple and noninvasive monitoring of
      biological processes in real-time. Here, we characterize the naturally secreted
      Vargula luciferase as a secreted blood reporter and show that this reporter can
      be multiplexed with the secreted Gaussia luciferase and alkaline phosphatase for
      simultaneous monitoring of three different cellular processes in the same
      biological system. We applied this system to monitor the response of three
      different subsets of glioma cells to a clinically relevant chemotherapeutic agent
      in the same well in culture or animal in vivo. This system could be extended to
      any field to detect multiple processes in the same biological system and is
      amenable for high-throughput screening to find drugs that affect multiple
      cellular populations/phenomena simultaneously. 

PMID- 24131225
TI  - Perceptions of randomized security schedules.
AB  - Security of infrastructure is a major concern. Traditional security schedules are
      unable to provide omnipresent coverage; consequently, adversaries can exploit
      predictable vulnerabilities to their advantage. Randomized security schedules,
      which randomly deploy security measures, overcome these limitations, but public
      perceptions of such schedules have not been examined. In this experiment,
      participants were asked to make a choice between attending a venue that employed
      a traditional (i.e., search everyone) or a random (i.e., a probability of being
      searched) security schedule. The absolute probability of detecting contraband was
      manipulated (i.e., 1/10, 1/4, 1/2) but equivalent between the two schedule types.
      In general, participants were indifferent to either security schedule, regardless
      of the probability of detection. The randomized schedule was deemed more
      convenient, but the traditional schedule was considered fairer and safer. There
      were no differences between traditional and random schedule in terms of perceived
      effectiveness or deterrence. Policy implications for the implementation and
      utilization of randomized schedules are discussed. 

PMID- 24131226
TI  - Fundus camera guided photoacoustic ophthalmoscopy.
AB  - PURPOSE: To demonstrate the feasibility of fundus camera guided photoacoustic
      ophthalmoscopy (PAOM) system and its multimodal imaging capabilities. METHODS: We
      integrated PAOM and a fundus camera consisting of a white-light illuminator and a
      high-sensitivity, high-speed CCD. The fundus camera captures both retinal anatomy
      and PAOM illumination at the same time to provide a real-time feedback when we
      position the PAOM illuminating light. We applied the integrated system to image
      rat eyes in vivo and used full-spectrum, visible (VIS), and near infrared (NIR)
      illuminations in fundus photography. RESULTS: Both albino and pigmented rat eyes
      were imaged in vivo. During alignment, different trajectories of PAOM laser
      scanning were successfully visualized by the fundus camera, which reduced the
      PAOM alignment time from several minutes to 30 s. In albino eyes, in addition to
      retinal vessels, main choroidal vessels were observed using VIS-illumination,
      which is similar to PAOM images. In pigmented eyes, the radial striations of
      retinal nerve fiber layer were visualized by fundus photography using full
      spectrum illumination; meanwhile, PAOM imaged both retinal vessels and the
      retinal pigmented epithelium melanin distribution. CONCLUSIONS: The results
      demonstrated that PAOM can be well-integrated with fundus camera without
      affecting its functionality. The fundus camera guidance is faster and easier
      comparing with our previous work. The integrated system also set the stage for
      the next-step verification between oximetry methods based on PAOM and fundus
      photography.

PMID- 24131227
TI  - Interaction between the premotor processes of eye and hand movements: possible
      mechanism underlying eye-hand coordination.
AB  - Interaction between the execution process of eye movement and that of hand
      movement must be indispensable for eye-hand coordination. The present study
      investigated corticospinal excitability in the hand muscles during the premotor
      processes of eye and/or hand movement to elucidate interaction between these
      processes. Healthy humans performed a precued reaction task of eye and/or finger
      movement and motor-evoked potentials in the hand muscles were evoked in the
      reaction time. Leftward eye movement suppressed corticospinal excitability in the
      right abductor digiti minimi muscle only when little finger abduction was
      simultaneously executed. Corticospinal excitability in the first dorsal
      interosseous muscle was not suppressed by eye movement regardless of whether or
      not it was accompanied by finger movement. Suppression of corticospinal
      excitability in the hand muscles induced by eye movement in the premotor period
      depends on the direction of eye movement, the muscle tested, and the premotor
      process of the tested muscle. The suppression may reflect interaction between the
      motor process of eye movement and that of hand movement particularly active
      during eye-hand coordination tasks during which both processes proceed.

PMID- 24131228
TI  - Influence of nongelling hydrocolloids on the gelation of agarose.
AB  - The combination of different gelling and nongelling hydrocolloids is known to
      yield complex systems with a wide range of mechanical properties. Here, the
      influence of the nongelling hydrocolloids sodium-alginate and xanthan on the
      gelation of agarose is investigated. The two polyelectrolytes differ
      significantly in their flexibility, leading to opposing effects on the
      thermomechanical properties of the resulting composite gels. The network
      structure of the agarose as well as viscoelasticity, gelling temperature, and
      thermal stability of the gels are altered. These properties are investigated by
      strain and temperature dependent oscillatory rheological measurements as well as
      confocal laser scanning microscopy. A phenomenological model to describe the
      network formation of agarose in the presence of alginate or xanthan respectively
      is presented. 

PMID- 24131230
TI  - An investigation of the international literature on nurse practitioner private
      practice models.
AB  - AIM: To investigate and synthesize the international literature surrounding nurse
      practitioner (NP) private practice models in order to provide an exposition of
      commonalities and differences. BACKGROUND: NP models of service delivery have
      been established internationally and most are based in the public healthcare
      system. In recent years, opportunities for the establishment of NP private
      practice models have evolved, facilitated by changes in legislation and driven by
      identification of potential patient need. To date, NP private practice models
      have received less attention in the literature and, to the authors' knowledge,
      this is the first international investigation of NP private practice models.
      DESIGN: Integrative literature review. METHOD: A literature search was undertaken
      in October 2012. Database sources utilized included Medical Literature Analyses
      and Retrieval (MEDLINE), the Cumulative Index of Nursing and Allied Health
      Literature (CINAHL), ProQuest, Scopus and the Cochrane Database of Systematic
      Reviews (CDSR). The grey literature was also searched. The following Medical
      Subject Headings (MeSH) and search terms used both individually and in
      combination included nurse practitioners; private practice; joint practice;
      collaboration; and insurance, health and reimbursement. Once literature had been
      identified, a thematic analysis was undertaken to extract themes. RESULTS: Thirty
      manuscripts and five publications from the grey literature were included in the
      final review. Private practice NP roles were identified in five countries, with
      the majority of the literature emanating from the USA. The thematic analysis
      resulted in the identification of five themes: reimbursement, collaborative
      arrangements, legislation, models of care and acceptability. CONCLUSION:
      Proportionally, there are very few NPs engaged in private practice
      internationally. The most common NP private practice models were community based,
      with NPs working in clinic settings, either alone or with other health
      professionals. Challenges in the context of legislation and financial
      reimbursement were identified in each country where private practice is being
      undertaken.

PMID- 24131231
TI  - Validation of the ambivalent and purposeful engagement--trait measure.
AB  - The Ambivalent and Purposeful Engagement-Trait Measure (APE-TM) was developed to
      assess two ways that people may react to stressful social interactions:
      ambivalent engagement (AE: counterproductive attempts to avoid thoughts and
      feelings) and purposeful engagement (PE: effortfully approaching and working
      through thoughts and feelings). We carried out three studies in undergraduate and
      clinical populations to (i) test the robustness of previous psychometric findings
      and (ii) determine whether AE and PE are specific to social anxiety. Across three
      studies, our results indicate that the APE-TM is a psychometrically valid measure
      of ambivalent and purposeful engagement. However, PE appeared less specific to
      social anxiety and may represent a more general tendency toward adaptive coping.
      In contrast, AE was specific to social anxiety in both undergraduate samples and
      clinical samples of individuals with a variety of anxiety disorders and
      depression. 

PMID- 24131232
TI  - The multifunctional role and therapeutic potential of HO-1 in the vascular
      endothelium.
AB  - SIGNIFICANCE: Heme oxygenases (HO-1 and HO-2) catalyze the degradation of the pro
      oxidant heme into carbon monoxide (CO), iron, and biliverdin, which is
      subsequently converted to bilirubin. In the vasculature, particular interest has
      focused on antioxidant and anti-inflammatory properties of the inducible HO-1
      isoform in the vascular endothelium. This review will present evidence that
      illustrates the potential therapeutic significance of HO-1 and its products, with
      special emphasis placed on their beneficial effects on the endothelium in
      vascular diseases. RECENT ADVANCES: The understanding of the molecular basis for
      the regulation and functions of HO-1 has led to the identification of a variety
      of drugs that increase HO-1 activity in the vascular endothelium. Moreover,
      therapeutic delivery of HO-1 products CO, biliverdin, and bilirubin has been
      shown to have favorable effects, notably on endothelial cells and in animal
      models of vascular disease. CRITICAL ISSUES: To date, mechanistic data
      identifying the downstream target genes utilized by HO-1 and its products to
      exert their actions remain relatively sparse. Likewise, studies in man to
      investigate the efficacy of therapeutics known to induce HO-1 or the consequences
      of the tissue-specific delivery of CO or biliverdin/bilirubin are rarely
      performed. FUTURE DIRECTIONS: Based on the promising in vivo data from animal
      models, clinical trials to explore the safety and efficacy of the therapeutic
      induction of HO-1 and the delivery of its products should now be pursued further,
      targeting, for example, patients with severe atherosclerotic disease, ischemic
      limbs, restenosis injury, or at high risk of organ rejection.

PMID- 24131233
TI  - A proposed liver needle core biopsy technique for the sharptooth catfish Clarias
      gariepinus (Burchell) for use in fish health research.

PMID- 24131234
TI  - Prenatal invasive testing: a 13-year single institution experience.
AB  - OBJECTIVES: To analyze trends in screening and invasive prenatal diagnosis over a
      13-year period in relation to changes in the national prenatal screening policy.
      METHODS: Fetal karyotypes obtained following 11 045 prenatal invasive procedures
      between January 1999 and December 2011 were retrospectively reviewed. Referral
      indications were classified as medical and non-medical (anxiety). The number of
      tests per relevant chromosomal abnormalities (CA) detected in both groups
      adjusted for indication was calculated. RESULTS: A total of 414 CA were detected
      (3.8%), 355 of which were considered clinically significant. The percentage of
      invasive procedures has declined from 49% to 12%, although cases referred by
      anxiety have increased from 22% to 55%. A total of 3129 invasive procedures did
      not have any medical indication (28%) and 13 relevant CA (0.42%) were found in
      this group. In this low-risk series, the index "number of invasive testing needed
      to detect 1 relevant CA" adjusted for indication was 241. CONCLUSIONS: Changes in
      our national prenatal policy through this 13-year period show an increasing
      efficiency of prenatal detection of CA. However, despite the intensifying
      screening policies, low-risk pregnant women show a growing demand for prenatal
      invasive testing and a baseline risk for cytogenetic abnormality of 1/241.

PMID- 24131235
TI  - Relationships between sources of health information and diabetes knowledge in the
      U.S. Hispanic population.
AB  - Data from the 2007 Hispanic Healthcare Survey were analyzed to examine the
      relationship between health information use and diabetes knowledge in the U.S.
      Hispanic population. A nationally representative sample of 4,013 adults self
      identified as Hispanics or Latinos was generated through stratified random digit
      dialing (RDD) and interviewed using Computer Assisted Telephone Interviewing
      (CATI). Results showed that receiving health information from health care
      providers, family and friends, newspapers and magazines, and the Internet was
      positively associated with diabetes knowledge. Getting health information from
      churches and community organizations, however, was negatively associated with
      diabetes knowledge. Use of television as a source of health information showed
      mixed results. Implications of these findings for diabetes interventions
      targeting the Hispanic population in the United States are discussed. 

PMID- 24131236
TI  - Survival, distribution, and translocation of Enterococcus faecalis and
      implications for pregnant mice.
AB  - Pregnant mothers are susceptible to bacterial infections, which may compromise
      the health of mothers and offspring. Enterococcus faecalis is a ubiquitous
      species found in food, restaurants, and hospitals where pregnant woman frequently
      become exposed to this bacterium. However, the survival, distribution,
      translocation, and corresponding influence of E. faecalis have not been
      investigated during the pregnancy period, when the mother and fetus are
      susceptible to bacterial infection. In this study, a fluorescing E. faecalis
      strain was used to track the fate of the bacterium in pregnant mice. Orally
      administered E. faecalis were found to survive and disseminate to all regions of
      the intestinal tract. It also altered the bacterial community structure by
      significantly decreasing the diversity of Lactobacillus species, impairing the
      normal structure and function of the intestinal barrier, which may contribute to
      the bacterial translocation into the blood, spleen, placenta, and fetus. This may
      affect fetal and placental growth and development. 

PMID- 24131237
TI  - Outcomes and Feasibility of a Manualized Cognitive-Behavioral Skills Building
      Intervention: Group COPE for Depressed and Anxious Adolescents in School
      Settings.
AB  - PROBLEM: Despite the increasing prevalence of depressive and anxiety disorders in
      adolescents, less than 25% of affected teens receive any treatment. METHODS: A
      preexperimental one-group pre- and posttest pilot study design with 4-week follow
      up was used to assess the feasibility and preliminary effects of the COPE
      (Creating Opportunities for Personal Empowerment) brief-focused manualized seven
      session cognitive-behavioral skills building group intervention delivered in two
      high schools to 16 adolescents referred by a school-based nurse practitioner for
      depression or elevated anxiety symptoms. FINDINGS: Adolescents reported
      significant decreases in depression and anxiety on the Beck Youth Inventory as
      well as increases in personal beliefs about managing negative emotions.
      Evaluations indicated that the group COPE intervention was a positive experience
      for the teens. CONCLUSIONS: COPE is a promising brief-focused cognitive
      behavioral therapy-based intervention that can be delivered effectively to teens
      in school settings using a group format.

PMID- 24131238
TI  - Calculating hyperfine couplings in large ionic crystals containing hundreds of QM
      atoms: subsystem DFT is the key.
AB  - We present an application of the linear scaling frozen density embedding (FDE)
      formulation of subsystem DFT to the calculation of isotropic hyperfine coupling
      constants (hfcc's) of atoms belonging to a guanine radical cation embedded in a
      guanine hydrochloride monohydrate crystal. The model systems range from an
      isolated guanine to a 15,000 atom QM/MM cluster where the QM region is comprised
      of 36 protonated guanine cations, 36 chlorine anions, and 42 water molecules. Our
      calculations show that the embedding effects of the surrounding crystal cannot be
      reproduced by small model systems nor by a pure QM/MM procedure. Instead, a large
      QM region is needed to fully capture the complicated nature of the embedding
      effects in this system. The unprecedented system size for a relativistic all
      electron isotropic hfcc calculation can be approached in this work because the
      local nature of the electronic structure of the organic crystals considered is
      fully captured by the FDE approach.

PMID- 24131239
TI  - Spectroscopic investigation of photoinduced charge-transfer processes in
      FTO/TiO2/N719 photoanodes with and without covalent attachment through silane
      based linkers.
AB  - Understanding electron-transfer (ET) processes in dye-sensitized solar cells
      (DSSCs) is crucial to improving their device performance. Recently, covalent
      attachment of dye molecules to mesoporous semiconductor nanoparticle films via
      molecular linkers has been employed to increase the stability of DSSC
      photoanodes. The power conversion efficiency (PCE) of these DSSCs, however, is
      lower than DSSCs with conventional unmodified photoanodes in this study.
      Ultrafast transient absorption pump-probe spectroscopy (TAPPS) has been used to
      study the electron injection process from N719 dye molecules to TiO2
      nanoparticles (NPs) in DSSC photoanodes with and without the presence of two
      silane-based linker molecules: 3-aminopropyltriethoxysilane (APTES) and p
      aminophenyltrimethoxysilane (APhS). Ultrafast biphasic electron injection
      kinetics were observed in all three photoanodes using a 530 nm pump wavelength
      and 860 nm probe wavelength. Both the slow and fast decay components, attributed
      to electron injection from singlet and triplet excited states, respectively, of
      the N719 dye to the TiO2 conduction band, are hindered by the molecular linkers.
      The hindering effect is less significant with the APhS linker than the APTES
      linker and is more significant for the singlet-state channel than the triplet
      state one. Electron injection from the vibrationally excited states is less
      affected by the linkers. The spectroscopic results are interpreted on the basis
      of the standard ET theory and can be used to guide selection of molecular linkers
      for DSSCs with better device performance. Other factors that affect the
      efficiency and stability of the DSSCs are also discussed. The relatively lower
      PCE of the covalently attached photoanodes is attributed to the multilayer and
      aggregation of the dye molecules as well as the linkers. 

PMID- 24131240
TI  - Proanthocyanidins from Spenceria ramalana and their effects on AGE formation in
      vitro and hyaloid-retinal vessel dilation in larval zebrafish in vivo.
AB  - Three new A-type proanthocyanidins (1-3), ent-epiafzelechin-(2alpha->O->7,4alpha
      >8)-ent-afzelechin 3'-O-beta-D-glycopyranoside (1), ent-epiafzelechin-(2alpha->O
      >7,4alpha->8)-ent-epiafzelechin-(2alpha->O->7,4alpha->8)-ent-afzelechin (2), and
      ent-epiafzelechin-(2alpha->O->7,4alpha->8)-ent-epicatechin-(2alpha->O->7,4alpha
      >8)-ent-afzelechin (3), and three known compounds (4-6) were isolated from the
      whole plant of Spenceria ramalana. The structures of the new proanthocyanidins
      were established by spectroscopic and chemical studies. The inhibitory effects of
      compounds 1-6 on the formation of advanced glycation end products were examined
      in vitro. Compounds 3 and 6 showed the strongest inhibition, with IC50 values of
      17.4 +/- 0.5 and 14.1 +/- 1.6 MUM, respectively. The effects of these isolates on
      the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval
      zebrafish were also investigated. Compound 3 reduced the dilation of HG-induced
      hyaloid-retinal vessels most effectively. This compound reduced the diameters of
      HG-induced hyaloid-retinal vessels by about 157.7% and 164.1% at 10 and 20 MUM,
      respectively, versus the HG-treated control group.

PMID- 24131241
TI  - Impact of SenseCam on memory, identity and mood in Korsakoff's syndrome: a single
      case experimental design study.
AB  - This study aimed to investigate the impact of SenseCam, a wearable, automatic
      camera, on subjective mood and identity in a patient with severe memory
      impairment due to Korsakoff's syndrome. It was hypothesised that SenseCam would
      improve Ms A's mood and identity through enhancing recall of autobiographical
      memories of recent events, therefore supporting a coherent sense of self; the
      lack of which was contributing to Ms A's mood deterioration. An ABA single case
      experimental design investigated whether using SenseCam to record regular
      activities impacted on Ms A's mood and identity. Ms A experienced improved recall
      for events recorded using SenseCam, and showed improvement on subjective ratings
      of identity. However, a corresponding improvement in mood was not seen, and the
      study was ended early at Ms A's request. Qualitative information was gathered to
      explore Ms A's experience of the study, and investigate psychosocial factors that
      may have impacted on the use of SenseCam. SenseCam may be of significant use as a
      compensatory memory aid for people with Korsakoff's syndrome and other types of
      alcohol-related brain damage (ARBD), but acceptance of memory impairment and
      consistent support may be among the factors required to support the use of such
      assistive technologies in a community setting. 

PMID- 24131242
TI  - Multilevel cross-dependent binary longitudinal data.
AB  - We provide insights into new methodology for the analysis of multilevel binary
      data observed longitudinally, when the repeated longitudinal measurements are
      correlated. The proposed model is logistic functional regression conditioned on
      three latent processes describing the within- and between-variability, and
      describing the cross-dependence of the repeated longitudinal measurements. We
      estimate the model components without employing mixed-effects modeling but
      assuming an approximation to the logistic link function. The primary objectives
      of this article are to highlight the challenges in the estimation of the model
      components, to compare two approximations to the logistic regression function,
      linear and exponential, and to discuss their advantages and limitations. The
      linear approximation is computationally efficient whereas the exponential
      approximation applies for rare events functional data. Our methods are inspired
      by and applied to a scientific experiment on spectral backscatter from long range
      infrared light detection and ranging (LIDAR) data. The models are general and
      relevant to many new binary functional data sets, with or without dependence
      between repeated functional measurements. 

PMID- 24131243
TI  - Synthesis and structural characterization of RE7Zn21Tt2 (RE = La-Nd; Tt = Ge, Sn,
      and Pb): new structure type among the polar intermetallic phases.
AB  - Reported are 11 new ternary phases with the general formula RE7Zn21Tt2 (RE = La
      Nd; Tt = Ge, Sn, and Pb), synthesized from the respective elements by reactions
      at high temperature. Their structures, established on the basis of single-crystal
      and powder X-ray diffraction work, are shown to be a new structure type with the
      orthorhombic space group Pbam (No. 55, Pearson symbol oP60). This complex atomic
      arrangement features condensed polyhedra made up of Zn atoms, interspersed by Ge,
      Sn, or Pb atoms in trigonal-planar coordination. The structure bears resemblance
      with the La3Al11 and the LaRhSn2 structure types, which are compared and
      discussed. Temperature dependent dc magnetization measurements confirm RE(3+)
      ground states for all rare-earth elements, and the expected local-moment
      magnetism due to the partial filling of their 4f states for RE(3+) = Ce(3+),
      Pr(3+), and Nd(3+). Theoretical considerations of the electronic structure based
      on the tight-binding linear muffin-tin orbital (TB-LMTO-ASA) method are also
      presented: the calculations support the experimental observation of a small, but
      not negligible, homogeneity range in RE7Zn(21+x)Tt(2-x) (x < 0.5). The partial
      substitution of the tetrel atoms by the electron-poorer Zn appears to be an
      important attribute, leading to an optimal valence electron concentration and,
      thereby, to the overall electronic stability of the crystal structure of this
      family of polar intermetallics.

PMID- 24131244
TI  - Evaluation of a high-sensitivity assay for measurement of canine and feline serum
      cardiac troponin I.
AB  - BACKGROUND: Cardiac troponins are established as the gold standard biomarkers for
      acute cardiac injury. As even small elevations of cardiac troponins have
      prognostic relevance in people, it is important to investigate the performance of
      sensitive assays for use in veterinary medicine. OBJECTIVES: The aim of this
      study was to evaluate analytical and overlap performance of a high-sensitivity
      cardiac troponin I (cTnI) assay, the ADVIA Centaur CP TnI-Ultra assay, in dogs
      and cats. METHODS: Serum samples from dogs and cats with cardiac disease or
      arrhythmias, along with samples of purified canine free cTnI and complexed cTnI,
      T, and C (cTnI-T-C) were used in the assay validation study. Intra- and inter
      assay variation, linearity under dilution, spike-and-recovery analysis, and
      detection limit were investigated to assess analytical performance. Overlap
      performance was evaluated based on the ability of the assay to discriminate
      between healthy animals and animals with cardiac disease or arrhythmias. RESULTS:
      Intra-assay variation of cTnI in canine and feline serum ranged from 3.9 to 6.4%
      and from 4.0 to 4.8%, respectively. Inter-assay variation ranged from 2.7 to 4.7%
      and from 4.0 to 7.8%, respectively. The assay demonstrated acceptable linearity
      under dilution within a clinically relevant range of cTnI concentrations. Spike
      and-recovery analysis showed excessive recovery in the range 150.7%-242.0% for
      free cTnI and 121.1-196.3% for complexed cTnI-T-C, partly due to a matrix effect.
      Overlap performance was acceptable as animals with cardiac disease or arrhythmias
      (n = 45 dogs, n = 53 cats) had significantly higher cTnI concentrations than
      healthy controls (P < .0001). CONCLUSIONS: The results confirm the ADVIA Centaur
      CP TnI-Ultra assay as a valuable tool for assessing cTnI and thus myocardial
      injury in dogs and cats.

PMID- 24131245
TI  - Treatment of subretinal fluid associated with dome-shaped macula.
AB  - Dome-shaped macula is a recently described disorder seen in eyes with myopic
      posterior staphyloma. Vision loss may accompany sub-macular fluid accumulation,
      for which no effective treatment has been reported. The authors report the
      successful treatment of two female patients, aged 34 and 59 years, with chronic
      exudative macular detachment associated with dome-shaped macula. Symptoms of
      subretinal fluid had been present for at least 2 years in each case, and the
      fluid was refractory to multiple intravitreal bevacizumab injections in one eye.
      After a single session of half-fluence verteporfin photodynamic therapy, the
      submacular fluid resolved completely in each eye. In one eye, recurrent
      submacular fluid 2 years later responded partially to repeat photodynamic therapy
      and completely to focal laser photocoagulation. [Ophthalmic Surg Lasers Imaging
      Retina. 2013;44:593-595.]. 

PMID- 24131246
TI  - Transfer of impact ejecta material from the surface of Mars to Phobos and Deimos.
AB  - The Russian Phobos-Grunt spacecraft originally planned to return a 200 g sample
      of surface material from Phobos to Earth. Although it was anticipated that this
      material would mainly be from the body of Phobos, there is a possibility that
      such a sample may also contain material ejected from the surface of Mars by large
      impacts. An analysis of this possibility is completed by using current knowledge
      of aspects of impact cratering on the surface of Mars and the production of high
      speed ejecta that might reach Phobos or Deimos.

PMID- 24131247
TI  - In situ colorimetric quantification of silver cations in the presence of silver
      nanoparticles.
AB  - Silver ions (Ag(+)) can be quantified in situ in the presence of AgNPs by using a
      colorimetric sensing probe (3,3',5,5'-tetramethylbenzidine). Interestingly, it
      also enables detection of the Ag(+) adsorbed on the AgNP surface. This is
      relevant to design new methods to make AgNPs while ensuring the total reduction
      of Ag(+). 

PMID- 24131248
TI  - TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic
      epithelial cells in response to rhinovirus infection.
AB  - BACKGROUND: Rhinoviruses (RV) are the most common acute triggers of asthma, and
      airway epithelial cells are the primary site of infection. Asthmatic bronchial
      epithelial cells (BECs) have been found to have impaired innate immune responses
      to RV. RV entry and replication is recognized by pathogen recognition receptors
      (PRRs), specifically toll-like receptor (TLR)3 and the RNA helicases; retinoic
      acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5
      (MDA5). OBJECTIVE: Our aim was to assess the relative importance of these PRRs in
      primary bronchial epithelial cells (pBEC) from healthy controls and asthmatics
      following RV infection and determine whether deficient innate immune responses in
      asthmatic pBECs were due to abnormal signalling via these PRRs. METHODS: The
      expression patterns and roles of TLR3 and MDA5 were investigated using siRNA
      knock-down, with subsequent RV1B infection in pBECs from each patient group. We
      also used BX795, a specific inhibitor of TBK1 and IKKi. RESULTS: Asthmatic pBECs
      had significantly reduced release of IL-6, CXCL-8 and IFN-lambda in response to
      RV1B infection compared with healthy pBECs. In healthy pBECs, siMDA5, siTLR3 and
      BX795 all reduced release of IL-6, CXCL-10 and IFN-lambda to infection. In
      contrast, in asthmatic pBECs where responses were already reduced, there was no
      further reduction in IL-6 and IFN-lambda, although there was in CXCL-10.
      CONCLUSION AND CLINICAL RELEVANCE: Impaired antiviral responses in asthmatic
      pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an
      inability to later activate types I and III interferon immune responses to RV
      infection, potentially increasing susceptibility to the effects of RV infection.

PMID- 24131249
TI  - Rethinking assessment measures of phonological development and their application
      in bilingual acquisition.
AB  - This article discusses the measurements for phonological and prosodic development
      put forward in Ingram [Ingram, D. (2002). The measurement of whole-word
      productions. Journal of Child Language, 29, 713-733.], while at the same time
      expanding the crucial measures, phonological mean length of utterance (PMLU) and
      proportion of whole-word proximity (PWP). The goal of the expansion is to
      accommodate a wider set of phenomena, specifically those related to bilingual
      acquisition of languages with different categories (e.g. closed syllables in
      German and open syllables in Spanish). Data from three monolingual Spanish
      children and from three bilingual German--Spanish children are presented as
      illustration of the modified measurements: expanded PMLU of features (ePMLU-F),
      expanded PMLU of syllables (ePMLU-S) and expanded PWP (ePWP). By means of
      measuring both features and prosodic positions, the expanded measurements do
      better justice to the various aspects of child phonology. Nonetheless, an
      important goal of this article is to stimulate discussion in order to bring our
      state-of-the-art closer to descriptive adequacy.

PMID- 24131250
TI  - My "big" blue health secret: my experience with privacy, or lack thereof, in
      Japan.

PMID- 24131251
TI  - Orientational dynamics in sum frequency spectroscopic line shapes.
AB  - We present a general response function formalism describing the contribution of
      orientational dynamics of molecules at interfaces to spectroscopic line shapes in
      vibrational sum frequency generation (SFG). When reorientation occurs on the time
      scale comparable to vibrational dephasing, its dynamics can be extracted from
      polarization-selected SFG spectral line shapes. Unique features of orientational
      motion at interfaces are (1) the anisotropic case-specific equilibrium
      orientational distribution and (2) possible dynamic anisotropy (e.g., different
      in-plane versus out-of-plane relaxation rates), both of which must be taken into
      account. Within the small-step rotational diffusion model, we present solutions
      for two cases, the weak-confinement model, applicable when the deviations from
      the isotropic case are not severe, and the wobbling-in-a-cone model, which
      considers a hard-wall orienting potential. SFG line shapes are calculated for a
      rod-like chromophore as a function of the rotational diffusion rate. For certain
      equilibrium orientational distributions, orientational dynamics may result in
      anomalous bi-Lorentzian line shapes (two Lorentzians of different widths centered
      and the same frequency). 

PMID- 24131252
TI  - Front line nurses' experiences with deteriorating ward patients: a qualitative
      study.
AB  - BACKGROUND: Nurses in the general ward are faced with patients who are at high
      risk of clinical deterioration. Having the key role in performing routine vital
      signs monitoring, non-registered nurses such as enrolled nurses are the front
      line nurses who play a pivotal role in detecting and responding to the
      deteriorating ward patient. AIMS: (1) To explore the experience of enrolled
      nurses with deteriorating patients in pre-cardiac arrest situations and (2) to
      identify strategies to enhance their role in caring for deteriorating ward
      patients. METHOD: A qualitative study using critical incident technique was
      conducted. Fifteen enrolled nurses who had encountered deteriorating ward
      patients were interviewed. Data were analysed using content analysis. FINDINGS:
      Three themes emerged describing enrolled nurse's experience with deteriorating
      patients: recognizing deterioration, responding to deterioration and taking
      responsibility. Two themes, including educational development and modifying
      clinical processes, were strategies identified to enhance the ability of enrolled
      nurses in recognizing and managing deteriorating patients. CONCLUSION: The study
      highlighted a need to enhance the ability of front line nurses in recognizing and
      responding to patient deterioration through nursing education and modifications
      of clinical processes. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing
      education could focus on increasing the awareness of the importance of performing
      complete vital signs monitoring and undertaking accurate interpretation of vital
      signs. Strategies to improve clinical processes could include the need for
      registered nurses to provide supervision of enrolled nurses in the interpretation
      of vital signs readings and share the responsibility of performing vital signs
      monitoring.

PMID- 24131253
TI  - Synthesis, structures, and properties of uranyl hybrids constructed by a variety
      of mono- and polycarboxylic acids.
AB  - A series of uranyl-organic coordination polymers have been hydrothermally
      synthesized by using a variety of carboxylic ligands, 3,3'-((2-((3
      carboxyphenoxy)methyl)-2-methylpropane-1,3-diyl)bis(oxy))dibenzoic acid (H3L(1)),
      4,4'-(3-(4-carboxyphenethyl)-3-hydroxypentane-1,5-diyl)dibenzoic acid (H3L(2)),
      chelidamic acid (H2L(3)), and benzoic acid (HL(4)) in the presence of N-bearing
      coligands, including 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 1-([1,1'
      biphenyl]-4-yl)-1H-imidazole (bpi), and 1,4-di(1H-imidazol-1-yl)benzene (dib).
      Compounds (UO2)(HL(1)) (1) and Zn(H2O)3(UO2)2(O)(OH)(L(2)).H2O (2) are
      constructed by semirigid ligands. The former is a one-dimensional ribbon-like
      structure with UO7 pentagonal bipyramids as the building unit, while the latter
      adopts a tetramer of UO7 pentagonal bipyramids to build a layered structure.
      Mononuclear UO7 pentagonal bipyramids are connected by L(3) groups to generate a
      two-dimensional arrangement of UO2(L(3))(H2dib)0.5 (3), in which the protonated
      dib molecules provide space filling and form pi...pi interactions with the
      layers. Compounds UO2(L(3))(phen) (4), UO2(L(3))2(Hbpi)2 (5), and
      UO2(L(4))2(bipy) (6) are molecular complexes, in which 4 and 6 are neutral, and 5
      comprises protonated bpi as the counterion. The uranyl center in compound 4 is
      chelated by one phen and one L(3) group to form a UO5N2 pentagonal bipyramid,
      while in compound 5, two L(3) groups are coordinated to an uranyl center,
      producing a UO8 polyhedron. Compound 6 consists of a UO6N2 polyhedron of uranyl
      unit coordinated by one bipy and two benzoate groups. Compounds
      Zn(phen)3[(UO2)(C2O4)(L(4))]2 (7) and Zn(bpi)2(UO2)(O)(C2O4)0.5(L(4)).H2O (8)
      feature one-dimensional structures. In 7, UO7 pentagonal bipyramids are
      alternatively connected by oxalate groups to form the chain, in which unidentate
      benzoate groups are coordinated to the uranium atoms. Zn(phen)3 cations fill the
      void space of the chains to compensate the negative charge. Differently, the
      chain of 8 can be seen as the heterometallic tetramer of UO7 and ZnO2N2 polyhedra
      connected by oxalate groups, and then bpi and benzoate groups are coordinated to
      the chain. All of the compounds have been characterized by IR and
      photoluminescent spectroscopy, and compounds 2, 3, 5, 6, and 8 exhibit
      characteristic emissions of uranyl cations. 

PMID- 24131254
TI  - Development of PLGA-mannosamine nanoparticles as oral protein carriers.
AB  - Here we report the development of polymeric nanoparticles, made of poly(lactide
      co-glycolide) (PLGA) chemically modified with mannosamine (MN), intended to
      specifically interact with the intestinal mucosa and facilitate the intestinal
      transport of proteins. PLGA-MN nanoparticles displayed nanometric size and a
      negative zeta potential, which was lower than that of the PLGA nanoparticles.
      This correlate well with the preferential location of the MN group on the
      nanoparticles surface obtained by X-ray photoelectron spectroscope (XPS). The
      presence of MN groups in the polymer chain led to a different surface morphology
      noted by SEM, an increase of the encapsulation of model proteins, and to help
      stabilizing the nanoparticles in simulated intestinal fluids. Furthermore, the MN
      modification significantly enhanced the nanoparticle's interaction with the
      epithelial cells in human intestinal follicle-associated epithelium cell culture
      model. Overall, the MN modification significantly modifies the properties of PLGA
      nanoparticles making them more suitable as nanocarriers for oral protein
      delivery. 

PMID- 24131255
TI  - Comparison of the buccal mucosal bleeding time in dogs using 3 different-sized
      lancet devices.
AB  - BACKGROUND: The buccal mucosal bleeding time (BMBT) evaluates primary hemostasis
      in vivo. Three different-sized lancet devices designed for people, Adult (A),
      Junior (J), and Newborn (N), can be used to perform the BMBT in dogs. OBJECTIVES:
      The aim was to compare BMBT using 3 different-sized human lancet devices in dogs
      with varying platelet counts and hematocrits. METHODS: The BMBT was measured in
      46 client-owned dogs (2 healthy, 44 suffering from various disorders) with
      varying platelet (Plt) counts and hematocrits, using the 3 devices successively
      in each dog, in a randomly determined order, over a 10- to 30-minute period.
      Statistical analysis (ANOVA, Mann-Whitney U-test) was performed using commercial
      software. RESULTS: BMBTs were significantly different between devices (P <
      .00001), and shorter with devices N and J compared with device A (P < .01). The
      BMBT was prolonged (> 210 s) in 10 dogs with device A and in 7 dogs each with
      devices J and N, respectively. Sixteen dogs had a Plt count < 200 * 10(9) /L
      (Reference interval 200-500 * 10(9) /L). Nine of these dogs had prolonged BMBT
      with device A, and 6 dogs with device J and device N, respectively. BMBT was
      longer in thrombocytopenic dogs with devices A and J (P < .016). Anemia without
      thrombocytopenia did not affect BMBT with any device. CONCLUSIONS: The BMBT is
      influenced by the size of the used device, with A resulting in the longest BMBT.
      Therefore, the type of device used to obtain the BMBT has to be specified for
      standardized results.

PMID- 24131260
TI  - Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta
      analysis of randomized controlled trials.
AB  - Dermatologists may choose from various conventional and biological systemic
      agents to treat patients with moderate-to-severe psoriasis. We set out to analyse
      systematically the efficacy and tolerability of approved treatments for moderate
      to-severe psoriasis. We undertook a systematic review and meta-analysis of
      randomized controlled trials (RCTs) investigating the efficacy of systemic
      treatment approved for moderate-to-severe psoriasis. Efficacy was assessed as the
      proportion of participants with 75% improvement in Psoriasis Area and Severity
      Index at primary efficacy measurement (week 8-16). Safety was summarized as rates
      of adverse events and withdrawals. Direct and indirect comparative efficacy was
      assessed by random effects meta-analysis of risk differences (RDs). In total, 48
      eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to
      conventional treatments) were identified. In placebo-controlled trials,
      infliximab was the most efficacious [RD 76%, 95% confidence interval (CI) 73
      79%]. Adalimumab (RD 61%, 95% CI 56-67%), and ustekinumab 45 mg (RD 63%, 95% CI
      59-66%) and 90 mg (RD 67%, 95% CI 60-74%) each had similar efficacy. These
      biologics are more effective than etanercept and all conventional treatments.
      Head-to-head trials indicate the superiority of adalimumab and infliximab over
      methotrexate (MTX), the superiority of ustekinumab over etanercept, the
      nonsignificant superiority of ciclosporin over MTX, and the dose-dependent
      efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX.
      Safety of treatments could not be pooled due to a lack of standardization in
      reporting across trials. In conclusion, the qualitative and quantitative evidence
      is much stronger for biological interventions than for conventional treatments.

PMID- 24131261
TI  - Drug misuse among university students in the UK: implications for prevention.
AB  - AIMS: The aim of the research was to identify the types of drugs currently being
      used by university students, their involvement in multiple drug misuse and drug
      combinations, and the consequences of drug misuse in terms of associated harms.
      METHODS: The research was based on an email survey of all first- and second-year
      students registered as undergraduates at a university in south Wales during
      October 2012. RESULTS: The results of the research showed that drug misuse on the
      university campus studied was widespread in terms of the types and patterns of
      drug misuse. The most troublesome findings concern the high levels of multiple
      drug use, the use of some of the most dangerous drugs (including crack and powder
      cocaine and heroin, as well as ketamine), and the list of recorded harms
      experienced as a result of drug misuse. CONCLUSIONS: The article concludes that
      little attention has been paid outside of the United States to drug use among
      university students or to interventions designed to prevent it. However, there
      are signs that government policy in the United Kingdom is beginning to pay
      attention to the specific problems of drug misuse among university students.

PMID- 24131263
TI  - Structure and hydrogen-bonding ability of estrogens studied in the gas phase.
AB  - The structures of estrogens (estrone(E1), beta-estradiol(E2), and estriol(E3))
      and their 1:1 hydrogen-bonded (hydrated) clusters with water formed in supersonic
      jets have been investigated by various laser spectroscopic methods and quantum
      chemical calculations. In the S1-S0 electronic spectra, all three species exhibit
      the band origin in the 35,050-35,200 cm(-1) region. By use of ultraviolet
      ultraviolet hole-burning (UV-UV HB) spectroscopy, two conformers, four
      conformers, and eight conformers, arising from different orientation of OH
      group(s) in the A-ring and D-ring, are identified for estrone, beta-estradiol,
      and estriol, respectively. The infrared-ultraviolet double-resonance (IR-UV DR)
      spectra in the OH stretching vibration are observed to discriminate different
      conformers of the D-ring OH for beta-estradiol and estriol, and it is suggested
      that in estriol only the intramolecular hydrogen bonded conformer exists in the
      jet. For the 1:1 hydrated cluster of estrogens, the S1-S0 electronic transition
      energies are quite different depending on whether the water molecule is bound to
      A-ring OH or D-ring OH. It is found that the water molecule prefers to form an H
      bond to the A-ring OH for estrone and beta-estradiol due to the higher acidity of
      phenolic OH than that of the alcoholic OH. On the other hand, in estriol the
      water molecule prefers to be bound to the D-ring OH due to the formation of a
      stable ring-structure H-bonding network with two OH groups. Thus, the
      substitution of one hydroxyl group to the D-ring drastically changes the hydrogen
      bonding preference of estrogens.

PMID- 24131262
TI  - Gender differences in stressful life events, social support, perceived stress,
      and alcohol use among older adults: results from a National Survey.
AB  - Stressful life events, perceived stress, and social support relationships with
      consumption, at-risk drinking, and alcohol use disorder (AUD) were studied in a
      population-based sample of current drinkers age 60+ in the National Epidemiologic
      Survey of Alcohol and Related Conditions (Wave 2; 2004-2005; n = 4,360).
      Stressful life events were associated with AUD among men and women, and crime
      victimization among men only. However, greater perceived stress was associated
      with lower consumption among women and greater odds of AUD in men, highlighting
      differences in the relationship between stress and alcohol use by gender that may
      be the result of the stress alcohol link. 

PMID- 24131264
TI  - MH II-DAB gene expression in grass carp Ctenopharyngodon idella (Valenciennes)
      after infection with the ciliate parasite, Ichthyophthirius multifiliis.
AB  - The grass carp, Ctenopharyngodon idella (Valenciennes), is one of the most
      extensively aquacultured freshwater fish in China. However, because of the lack
      of effective control measures and the high-density culture environment,
      considerable economic losses are caused by infection of C. idella with the
      parasitic ciliate, Ichthyophthirius multifiliis. The major histocompatibility
      (MH) DAB gene belongs to antigen-presented genes in the class II genomic region,
      which is associated with parasite resistance. To understand the relationship of
      the DAB gene with I. multifiliis infection in grass carp, the expression profiles
      of MH II-DAB were studied in tissues using real-time quantitative polymerase
      chain reaction. The results showed that expression of the MH II-DAB gene was up
      regulated in head kidney after I. multifiliis infection, and the expression peak
      appeared earlier in the study (case) group than in the control group. The obvious
      up-regulation peak of MH II-DAB gene was found at days 2 and 4 in skin; at 12 h
      to day 4 in spleen; at 12 h and days 1 and 6 in gill; and at day 10 in blood,
      whereas the MH II-DAB gene was down-regulated in liver and intestines after I.
      multifiliis infection. These results have implications for better understanding
      C. idella resistance to I. multifiliis infection.

PMID- 24131265
TI  - Evaluation of the RAAPS Risk Screening Tool for Use in Detecting Adolescents With
      Depression.
AB  - PROBLEM: Screening is vital to quality adolescent care, but using multiple
      surveys to screen depression and interrelated risk behaviors is difficult. The
      aim of this study was to evaluate RAAPS (Rapid Assessment for Adolescent
      Preventive Services) effectiveness as a screening tool for adolescent depression.
      METHODS: Cronbach's alpha, area under the receiver operating characteristic (ROC)
      curve, sensitivity, specificity, and positive and negative predictive values were
      assessed. FINDINGS: Cronbach's alpha was 0.66 overall. The ROC curve is 0.86.
      Sensitivity and specificity were 0.86 and 0.71, respectively. The positive
      predictive value is 0.46 and the negative predictive value is 0.95. CONCLUSION:
      Results indicate RAAPS may be an effective screening tool for identifying
      adolescent depression.

PMID- 24131270
TI  - Artificial neural network-based classification of body movements in ambulatory
      ECG signal.
AB  - Abstract Ambulatory ECG monitoring provides electrical activity of the heart when
      a person is involved in doing normal routine activities. Thus, the recorded ECG
      signal consists of cardiac signal along with motion artifacts introduced due to a
      person's body movements during routine activities. Detection of motion artifacts
      due to different physical activities might help in further cardiac diagnosis.
      Ambulatory ECG signal analysis for detection of various motion artifacts using
      adaptive filtering approach is addressed in this paper. We have used BIOPAC MP 36
      system for acquiring ECG signal. The ECG signals of five healthy subjects (aged
      between 22-30 years) were recorded while the person performed various body
      movements like up and down movement of the left hand, up and down movement of the
      right hand, waist twisting movement while standing and change from sitting down
      on a chair to standing up movement in lead I configuration. An adaptive filter
      based approach has been used to extract the motion artifact component from the
      ambulatory ECG signal. The features of motion artifact signal, extracted using
      Gabor transform, have been used to train the artificial neural network (ANN) for
      classifying body movements. 

PMID- 24131271
TI  - Managing a child with possible allergy to vaccine.
AB  - Similarly to other medications, vaccines may be responsible for allergic
      reactions. Although IgE-mediated allergies to vaccine are extremely rare, they
      are clearly overdiagnosed. Indeed, accurate diagnosis of vaccine allergy is
      important not only to prevent serious or even life-threatening reactions, but
      also to avoid unnecessary vaccine restriction. Systematic approaches have been
      proposed and, if implemented, will likely reduce the number of children being
      inappropriately labeled as allergic to vaccine. In diagnosis of vaccine allergy,
      the patient's history is central although not sufficient. In case of suspicion of
      an allergy, the child should be referred to an allergist in order to perform a
      complete allergy workup, based primarily on skin tests and/or specific IgE.
      Highlighting the most recent literature, this article will address the management
      of children with a possible allergy to vaccine.

PMID- 24131272
TI  - Comparison of registered and published primary outcomes in randomized controlled
      trials of gastroenterology and hepatology.
AB  - OBJECTIVES. The need for trial registration as well as the benefits it has
      brought for the transparency of medical research has been recognized for years.
      Trial registration has turned from an exception to a mandatory guideline in
      recent years. The present study aimed to examine the characteristics of
      registered randomized controlled trials (RCTs) in a sample of recently published
      gastroenterology RCTs, and to assess the consistency of registered and published
      primary outcome (PO) in RCTs. METHODS. Articles published in the top five
      "general and internal journals" and top five "gastroenterology and hepatology
      journals" categories between 2009 and 2012 were searched in PubMed. Basic
      characteristics and the registration information were identified and extracted
      from the included RCTs. PO consistency analysis was conducted to compare between
      the registered and published format. RESULTS. A total of 305 RCTs were included;
      among them 252 could be identified with a registration number. Nearly half of
      these RCTs were funded solely by industry (141/305, 46.3%). ClinicalTrials.gov
      was the most popular registry for these RCTs (214/252, 84.9%). A total of 155
      RCTs were included in the PO consistency analysis. Among them, 22 (14.2%) RCTs
      had discrepancies between POs registered in the trial registry compared to the
      published article. CONCLUSIONS. Based on the results of the present study,
      selective outcome reporting of gastroenterology RCTs published in leading medical
      journals has been much improved over the past years. However, there might be a
      sampling bias to say that consistency of registered and published POs of
      gastroenterology RCTs has been better than before.

PMID- 24131273
TI  - Attentional sets influence perceptual load effects, but not dilution effects.
AB  - Perceptual load theory [Lavie, N. (1995). Perceptual load as a necessary
      condition for selective attention. Journal of Experimental Psychology: Human
      Perception and Performance, 21, 451-468.; Lavie, N., & Tsal, Y. (1994) Perceptual
      load as a major determinant of the locus of selection in visual attention.
      Perception & Psychophysics, 56, 183-197.] proposes that interference from
      distractors can only be avoided in situations of high perceptual load. This
      theory has been supported by blocked design manipulations separating low load
      (when the target appears alone) and high load (when the target is embedded among
      neutral letters). Tsal and Benoni [(2010a). Diluting the burden of load:
      Perceptual load effects are simply dilution effects. Journal of Experimental
      Psychology: Human Perception and Performance, 36, 1645-1656.; Benoni, H., & Tsal,
      Y. (2010). Where have we gone wrong? Perceptual load does not affect selective
      attention. Vision Research, 50, 1292-1298.] have recently shown that these
      manipulations confound perceptual load with "dilution" (the mere presence of
      additional heterogeneous items in high-load situations). Theeuwes, Kramer, and
      Belopolsky [(2004). Attentional set interacts with perceptual load in visual
      search. Psychonomic Bulletin & Review, 11, 697-702.] independently questioned
      load theory by suggesting that attentional sets might also affect distractor
      interference. When high load and low load were intermixed, and participants could
      not prepare for the presentation that followed, both the low-load and high-load
      trials showed distractor interference. This result may also challenge the
      dilution account, which proposes a stimulus-driven mechanism. In the current
      study, we presented subjects with both fixed and mixed blocks, including a mix of
      dilution trials with low-load trials and with high-load trials. We thus separated
      the effect of dilution from load and tested the influence of attentional sets on
      each component. The results revealed that whereas perceptual load effects are
      influenced by attentional sets, the dilution component is not. This strengthens
      the notion that dilution is a stimulus-driven mechanism, which enables effective
      selectivity.

PMID- 24131274
TI  - Epidemiology, pathophysiology, and the future of ocular toxoplasmosis.
AB  - Despite large advances in the field of ocular toxoplasmosis, large gaps still
      exist in our knowledge concerning the epidemiology and pathophysiology of this
      potentially blinding infectious disease. Although ocular toxoplasmosis is
      considered to have a high health burden, still little is known about its exact
      prevalence and how it affects the quality of life. The epidemiology of
      toxoplasmosis depends on local habits throughout the globe, and changes are
      likely in view of increased meat consumption in developing countries and demands
      for higher animal welfare in the Western world. Water is increasingly seen as an
      important risk factor and more studies are needed to quantitate and control the
      role of water exposure (drinking, swimming). Tools are now becoming available to
      study both the human host as well as parasite genetic factors in the development
      of ocular toxoplasmosis. Further research on the role of Toxoplasma strains as
      well as basic studies on parasite virulence is needed to explain why Toxoplasma
      associated eye disease is so severe in some countries, such as Brazil. Although
      genetic analysis of the parasite represents the gold standard, further
      developments in serotyping using peptide arrays may offer practical solutions to
      study the role of parasite strains in the pathogenesis of Toxoplasma
      retinochoroiditis. More research is needed concerning the pathways whereby the
      parasite can infect the retina. Once in the retina further tissue damage may be
      due to parasite virulence factors or could be caused by an aberrant host immune
      response. Local intraocular immune responses are nowadays used for diagnostic
      procedures. Future developments may include the use of Raman technology or the
      direct visualization of a Toxoplasma cyst by optical coherence tomography (OCT).
      With the availability of ocular fluid specimens obtained for diagnostic purposes
      and the development of advanced proteomic techniques, a biomarker fingerprint
      that is unique for an eye with toxoplasmosis may become available. It is hoped
      that such a biomarker analysis may also be able to distinguish between acquired
      versus congenital disease. Recently developed mouse models of congenital ocular
      toxoplasmosis are extremely promising with regard to disease pathogenesis,
      diagnosis, and treatment.

PMID- 24131276
TI  - Using fluorescence lifetime imaging microscopy to monitor theranostic
      nanoparticle uptake and intracellular doxorubicin release.
AB  - We describe the synthesis of iron oxide nanoparticles (IONPs) with excellent
      colloidal stability in both water and serum, imparted by carefully designed
      grafted polymer shells. The polymer shells were built with attached aldehyde
      functionality to enable the reversible attachment of doxorubicin (DOX) via imine
      bonds, providing a controlled release mechanism for DOX in acidic environments.
      The IONPs were shown to be readily taken up by cell lines (MCF-7 breast cancer
      cells and H1299 lung cancer cells), and intracellular release of DOX was proven
      using in vitro fluorescence lifetime imaging microscopy (FLIM) measurements.
      Using the fluorescence lifetime difference exhibited by native DOX (~1 ns)
      compared to conjugated DOX (~4.6 ns), the intracellular release of conjugated DOX
      was in situ monitored in H1299 and was estimated using phasor plot
      representation, showing a clear increase of native DOX with time. The results
      obtained from FLIM were corroborated using confocal microscopy, clearly showing
      DOX accumulation in the nuclei. The IONPs were also assessed as MRI negative
      contrast agents. We observed a significant change in the transverse relaxivity
      properties of the IONPs, going from 220 to 390 mM(-1) s(-1), in the presence or
      absence of conjugated DOX. This dependence of MRI signal on IONP-DOX/water
      interactions may be exploited in future theranostic applications. The in vitro
      studies were then extended to monitor cell uptake of the DOX loaded IONPs
      (IONP@P(HBA)-b-P(OEGA) + DOX) into two 3D multicellular tumor spheroids (MCS)
      grown from two independent cell lines (MCF-7 and H1299) using multiphoton
      excitation microscopy.

PMID- 24131277
TI  - Clarifying the link between traumatic brain injury and homelessness: workshop
      proceedings.
AB  - PURPOSE: To disseminate the proceedings of a 1-day multidisciplinary stakeholder
      workshop aimed at examining the inter-relationship between traumatic brain injury
      (TBI) and homelessness. METHODS: Thirty-seven stakeholders participated in the
      workshop, including frontline workers with individuals who are homeless,
      physicians, nurses and other healthcare workers, researchers, policy-makers,
      students and individuals with lived experience of homelessness. Didactic
      presentations, large group discussions and break-out sessions were used to
      disseminate knowledge, identify service and research gaps, develop a research
      agenda and facilitate networking. RESULTS: The participants identified barriers
      to service provision for individuals who are homeless and have sustained TBI with
      a focus on age- and gender-related issues, co-morbid TBI and mental illness and
      jurisdictional differences. Challenges and strategies related to engaging
      stakeholders in research with this population, as well as disseminating knowledge
      were discussed and research questions were identified. CONCLUSION: There is very
      little empirical literature on the topic of TBI and homelessness. The workshop
      identified key issues for consideration, including gaps in knowledge related to
      this topic.

PMID- 24131275
TI  - beta-2 adrenergic receptor gene methylation is associated with decreased asthma
      severity in inner-city schoolchildren: asthma and rhinitis.
AB  - BACKGROUND: Genetic variation in the beta-2 adrenergic receptor gene (ADRB2) has
      been implicated in asthma severity and control with conflicting results.
      Epigenetic variation in the ADRB2 may play an important role in asthma phenotype.
      OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated
      with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG
      sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled
      in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured
      by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage
      DNA methylation across the sites was evaluated for association with asthma
      severity (report of dyspnoea, night-time symptoms, rescue medication use, and
      baseline spirometry) and morbidity (school absences and unscheduled healthcare
      visits). Three clades composed of highly correlated methylation sites within the
      methylated segment of ADRB2 were further analysed. RESULTS: Methylation of
      individual sites generally ranged from 0% to 6% with average percentage
      methylation across sites of 2.4%. Univariate analyses strongly favoured the
      association of higher percentage methylation with lower asthma severity measured
      by report of dyspnoea. Furthermore, there was a non-significant trend towards
      less rescue medication use, night-time symptoms, school absences, activity
      limitation due to asthma, and improved lung function measurements with increased
      methylation. Multivariate analysis demonstrated methylation of ADRB2 gene
      significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence
      interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites
      showed a strong, but not statistically significant, effect on decreased dyspnoea.
      CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is
      associated with decreased asthma symptom severity, suggesting a role for
      methylation in asthma phenotypes.

PMID- 24131278
TI  - Microfabricated tin-film electrodes for protein and DNA sensing based on
      stripping voltammetric detection of Cd(II) released from quantum dots labels.
AB  - A novel disposable microfabricated tin-film electrochemical sensor was developed
      for the detection of proteins and DNA. The sensor was fabricated on a silicon
      wafer through photolithography to define the sensor geometry followed by tin
      sputtering. A sandwich-type immunoassay with biotinylated reporter antibody was
      employed for the determination of prostate-specific antigen (PSA) in human serum
      samples. For the detection of C533G mutation of the RET gene, biotinylated
      oligonucleotide probes were used. The biotinylated biomolecular probes were
      labeled with streptavidin (STV)-conjugated CdSe/ZnS quantum dots (QDs);
      quantification of the analytes was performed through acidic dissolution of the
      QDs and stripping voltammetric detection of the Cd(II) released. The proposed QD
      based electrochemical sensor overcomes the limitations of existing voltammetric
      sensors and provides a mercury-free sensing platform with scope for mass
      production and further potential for application in clinical diagnostics. 

PMID- 24131280
TI  - Biodegradable electrospun scaffolds for annulus fibrosus tissue engineering:
      effect of scaffold structure and composition on annulus fibrosus cells in vitro.
AB  - Electrospinning technology is an attractive process for the fabrication of a
      scaffold with an annulus fibrosus (AF)-like architecture for tissue engineering.
      Oriented and nonoriented electrospun scaffolds were prepared from poly(ester
      urethane) (PU) and poly(E-caprolactone) (PCL) as well as corresponding
      homogeneous films. Scaffolds' characteristics and mechanical properties were
      characterized by scanning electron microscopy, static water contact measurements,
      and dynamic mechanical analysis, respectively. The effect of scaffold
      architecture and polymer composition on bovine AF cells was investigated. PU and
      PCL films and scaffolds supported AF cell growth and extracellular matrix
      production and accumulation. Electrospun scaffolds increased the retention of
      collagen and glycosaminoglycan compared with films. Fiber orientation of the
      scaffolds promoted the AF cell phenotype with a trend toward an upregulation of
      matrix gene expression for oriented relative to nonoriented scaffolds. The higher
      yield strain of an oriented electrospun PU scaffold, compared with other
      scaffolds, will be advantageous for AF tissue engineering under a dynamic
      mechanical environment. 

PMID- 24131281
TI  - Informing youth about the age of sexual initiation using means or percentages.
AB  - The common statistical indicator "mean age of first sex" can be misinterpreted by
      youth to indicate that most of their peers of the same age are sexually
      initiated, when this is not usually the case. This can jeopardize efforts to
      delay sexual initiation. University students were randomly assigned to one of two
      versions of an anonymous survey. They were asked to estimate how common sexual
      initiation was at a given age upon being presented with statements with different
      wordings, such as the "mean age of first sex" or "proportions of youth at
      different ages having had sex." Their interpretations were compared using
      logistic regression. Students who were assigned surveys using the indicator "mean
      age" of sexual initiation had higher odds of overestimating the extent of sexual
      initiation compared to those assigned surveys using percentages as the indicator,
      even after adjusting for student's sex and degree. We encourage the use of the
      "percentage" of youth, at different ages, who are sexually initiated as a more
      reliable indicator. 

PMID- 24131282
TI  - BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease, affecting
      more than 2.5 million people worldwide with more 400,000 cases in the United
      States alone. There has been considerable improvement in the treatment of MS,
      with the introduction of disease-modifying drugs; however, new oral therapies may
      provide additional benefit by providing an alternative treatment modality and the
      potential for improved adherence by avoiding the injection-associated side
      effects and anxiety encountered with some first-line agents. BG-12 (dimethyl
      fumarate) is an oral agent approved in the United States for the treatment of
      relapsing forms of MS. SCOPE: We review published literature about what is known
      about the mechanism of action of BG-12, and key efficacy and safety findings from
      three clinical studies in patients with relapsing-remitting MS (RRMS). FINDINGS:
      Data from preclinical studies have demonstrated that BG-12 may promote anti
      inflammatory and cytoprotective activities that are mediated, at least in part,
      by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response
      pathway. Studies in animals have shown a protective effect of BG-12 on neuronal,
      axonal and myelin integrity. Results from a phase 2 study and two randomized
      double-blind placebo-controlled phase 3 studies, CONFIRM and DEFINE, have shown
      that BG-12 provides clinical and radiologic efficacy in patients with RRMS. At 2
      years, BG-12 240 mg twice and three times daily reduced annualized relapse rate
      (CONFIRM primary endpoint) by 44% and 51% and the risk of relapse (DEFINE primary
      endpoint) by 49% and 50%, respectively, compared with placebo (all p < 0.001). BG
      12 was generally well tolerated and had an acceptable safety profile, with a
      similar incidence of adverse events across treatment groups. CONCLUSIONS: BG-12
      may have cytoprotective and anti-inflammatory properties that contribute to its
      efficacy among patients with RRMS. Findings from phase 2 and 3 studies further
      support BG-12 as an effective initial therapy. ClinicalTrials.gov ID:
      NCT00168701; NCT00420212: NCT00451451.

PMID- 24131283
TI  - Organic aerosol mixing observed by single-particle mass spectrometry.
AB  - We present direct measurements of mixing between separately prepared organic
      aerosol populations in a smog chamber using single-particle mass spectra from the
      high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). Docosane
      and docosane-d46 (22 carbon linear solid alkane) did not show any signs of
      mixing, but squalane and squalane-d62 (30 carbon branched liquid alkane) mixed on
      the time scale expected from a condensational-mixing model. Docosane and docosane
      d46 were driven to mix when the chamber temperature was elevated above the
      melting point for docosane. Docosane vapors were shown to mix into squalane-d62,
      but not the other way around. These results are consistent with low diffusivity
      in the solid phase of docosane particles. We performed mixing experiments on
      secondary organic aerosol (SOA) surrogate systems finding that SOA derived from
      toluene-d8 (a surrogate for anthropogenic SOA (aSOA)) does not mix into squalane
      (a surrogate for hydrophobic primary organic aerosol (POA)) but does mix into SOA
      derived from alpha-pinene (biogenic SOA (bSOA) surrogate). For the aSOA/POA, the
      volatility of either aerosol does not limit gas-phase diffusion, indicating that
      the two particle populations do not mix simply because they are immiscible. In
      the aSOA/bSOA system, the presence of toluene-d8-derived SOA molecules in the
      alpha-pinene-derived SOA provides evidence that the diffusion coefficient in
      alpha-pinene-derived SOA is high enough for mixing on the time scale of 1 min.
      The observations from all of these mixing experiments are generally invisible to
      bulk aerosol composition measurements but are made possible with single-particle
      composition data. 

PMID- 24131284
TI  - Development and characterization of 14 microsatellite loci in the Neotropical
      fish Geophagus brasiliensis (Perciformes, Cichlidae).
AB  - Fourteen polymorphic microsatellite loci were isolated and characterized for the
      Neotropical cichlid Geophagus brasiliensis and tested on 30 individuals belonging
      to a single population. Among the 14 loci described, four showed potential
      presence of null alleles, inferred from the excess of homozygous genotypes, and
      three of these loci showed significant deviations from Hardy-Weinberg
      equilibrium. Fifty-nine different alleles were detected (ranging from two to
      eight alleles per locus), with estimates of observed and expected heterozygosity
      ranging from 0.167 to 0.700 and from 0.269 to 0.825. Cross-amplification of
      primers was successful in five other cichlid species. 

PMID- 24131285
TI  - Manual corneal thickness measurements of healthy equine eyes using a portable
      spectral-domain optical coherence tomography device.
AB  - REASONS FOR PERFORMING STUDY: Corneal thickness measurements of the equine globe
      using spectral-domain optical coherence tomography (SD-OCT) have not been
      reported. OBJECTIVES: To determine corneal thickness measurements and the intra-
      and interoperator reliability of a portable SD-OCT device in equine eyes. STUDY
      DESIGN: Prospective observational study. METHODS: Horses free of ocular disease
      were used for this study. Gentle manual restraint, in combination with detomidine
      hydrochloride and a head stand, were employed to ensure proper animal
      positioning. Corneal pachymetry measurements were obtained from both eyes of each
      animal 3 times by 2 operators in succession. A 6 mm corneal pachymetry protocol
      was performed using a portable SD-OCT device. All measurements were obtained
      manually by one operator (C.G.P.) using the integrated calliper function.
      Measurements included epithelial thickness, stromal thickness, Descemet's
      membrane thickness and total corneal thickness. All recorded measurements were
      analysed to determine both intra- and interoperator reliability. RESULTS: Thirty
      horses with a mean age of 10.6 +/- 6.4 years were examined. Mean epithelial,
      stromal, Descemet's membrane and total corneal thickness values obtained were,
      respectively, 174.7 +/- 13.6, 599.2 +/- 45.4, 38.4 +/- 15.3 and 812.0 +/- 44.1
      MUm for operator A and 175.9 +/- 12.9, 599.2 +/- 44.9, 38.4 +/- 15.0 and 812.9 +/
      42.9 MUm for operator B. A positive correlation was found between Descemet's
      membrane thickness and age, whereby Descemet's membrane thickness increased by 2
      MUm/year (P<0.0001). The coefficients of variation for both operators were <4%
      for all measurements. Intraclass correlations ranged from 0.92 to 0.98.
      CONCLUSIONS: Manual corneal thickness measurement using a portable SD-OCT device
      provides epithelial, stromal, Descemet's membrane and total corneal thickness
      measurements with clinically acceptable intra- and interoperator reliability in
      healthy equine eyes.

PMID- 24131286
TI  - Vitiligo: an evidence-based update. Report of the 13th Evidence Based Update
      Meeting, 23 May 2013, Loughborough, U.K.
AB  - The Evidence Based Update (EBU) meetings are annual one-day meetings held by the
      Centre of Evidence Based Dermatology at the University of Nottingham. The aim of
      the meeting is to discuss high-quality evidence, mainly in the form of systematic
      reviews and randomized controlled trials, on a different topic each year. The
      meetings are designed to be interactive with a panel discussion between
      international experts and delegates forming a key part of the meeting. The 13th
      EBU meeting was on vitiligo and took place on 23 May 2013 in Loughborough, U.K.
      The most recent research including new and unpublished studies was presented on
      the classification of vitiligo, the evidence behind different treatment options
      and current guidelines for vitiligo. 

PMID- 24131288
TI  - Safety of staged interpolation flaps after Mohs micrographic surgery in an
      outpatient setting: a single-center experience.
AB  - OBJECTIVE: To establish the safety of staged interpolation flaps performed in an
      outpatient dermatologic clinic setting. METHODS: A retrospective chart review was
      performed of patients who underwent staged interpolation flap reconstruction by a
      single dermatologic surgeon after tumor clearance using Mohs micrographic surgery
      from 2000 to 2012 at the Department of Dermatology, Medical University of South
      Carolina. RESULTS: Six hundred fifty-three staged flaps were performed in 639
      patients (mean age 65) between June 2000 and November 2012. Types of flaps
      included paramedian forehead flaps (n = 291, 45%), two-stage melolabial flaps (n
      = 256, 39%), retroauricular flaps (n = 58, 9%), interpolated paranasal flaps (n =
      40, 6%), and Abbe or Abbe-Estlander flaps (n = 8, 1%). No major complications
      were observed. Of the minor complications, problems related to bleeding were the
      most prevalent; active bleeding requiring physician intervention was seen in 8.4%
      and hematoma formation in 0.4% of flaps. Postoperative infections were seen in
      1.7% of patients after the initial surgery and 3.4% after division of the
      pedicle. Primary or secondary dehiscence was seen in 0.5%. Partial full-thickness
      flap necrosis was seen in 2.3% and total flap necrosis in 0.6%. CONCLUSION: The
      rate of complications associated with dermatologic surgeons performing
      interpolated flaps in an outpatient setting under local anesthesia is low. Our
      complication rates are equal to or lower than published complication rates from
      other surgical specialties.

PMID- 24131287
TI  - Bioactive cellulose nanofibrils for specific human IgG binding.
AB  - Bioactive films were produced by conjugation of a short peptide onto modified
      cellulose nanofibrils (CNF). Specifically, a hydrophilic copolymer, poly(2
      aminoethyl methacrylate hydrochloride-co-2-hydroxyethylmethacrylate) (poly(AMA-co
      HEMA)), was grafted via surface initiated polymerization from an initiator
      coupled to CNF. The poly(AMA-co-HEMA) was used as a spacer and support layer for
      immobilization of the peptide, acetylated-HWRGWVA, which has specific affinity
      with human immunoglobulin G (hIgG). Two methods for peptide grafting were
      compared: modification of CNF in aqueous suspension followed by assembly into a
      bioactive film and peptide grafting on a preformed CNF film. The CNF-based
      networks were examined on solid supports via atomic force microscopy (AFM) and
      extreme resolution imaging with ultralow electron landing energies (scanning low
      energy electron microscopy). The specific binding capability of hIgG and
      nonspecific protein resistance of the resultant peptide-modified CNF were
      evaluated by using quartz crystal microgravimetry (QCM). The effects of initiator
      concentration and thickness of poly(AMA-co-HEMA) layer on hIgG adsorption were
      investigated in the developed systems, which exhibited high signal-to-noise
      response. 

PMID- 24131290
TI  - The backside of graphene: manipulating adsorption by intercalation.
AB  - The ease by which graphene is affected through contact with other materials is
      one of its unique features and defines an integral part of its potential for
      applications. Here, it will be demonstrated that intercalation, the insertion of
      atomic layers in between the backside of graphene and the supporting substrate,
      is an efficient tool to change its interaction with the environment on the
      frontside. By partial intercalation of graphene on Ir(111) with Eu or Cs we
      induce strongly n-doped graphene patches through the contact with these
      intercalants. They coexist with nonintercalated, slightly p-doped graphene
      patches. We employ these backside doping patterns to directly visualize doping
      induced binding energy differences of ionic adsorbates to graphene through low
      temperature scanning tunneling microscopy. Density functional theory confirms
      these binding energy differences and shows that they are related to the graphene
      doping level. 

PMID- 24131291
TI  - Structural dynamism and controlled chemical blocking/unblocking of active
      coordination space of a soft porous crystal.
AB  - A three-dimensional biporous soft porous coordination polymer containing active
      coordination space, made of cadmium(II) and a tripodal carboxylate ligand bearing
      ether linkages, was synthesized and characterized. Guest-dependent dynamic
      activities in the active coordination space of the soft porous crystal have been
      explored. We have demonstrated controlled chemical blocking and unblocking of
      active pores of the dynamic framework along with guest-dependent contraction and
      expansion of the channels by single-crystal-to-single-crystal structural
      transformation studies. Detailed studies revealed up to 70% contraction of the
      void volume and almost a 100 times increase in gas sorption by controlled phases
      obtained by guest switching. These types of soft materials with porous scaffolds,
      also known as soft porous crystals, may have general implications in the
      preparation of intelligent host materials with zeolitic properties and enzyme
      like specificity. 

PMID- 24131292
TI  - AAP President's Address.

PMID- 24131293
TI  - Care dependency in patients with chronic obstructive pulmonary disease and heart
      failure - a secondary data analysis of German prevalence studies.
AB  - AIM: The aim of this study was to compare the degree of care dependency between
      hospitalised patients with chronic heart failure (CHF) and patients with chronic
      obstructive pulmonary disease (COPD). METHODS: Secondary data analysis of five
      German prevalence studies from 2007 to 2011. Care dependency was measured using
      the Care Dependency Scale. RESULTS: Hospitalised patients with CHF or COPD are to
      a limited extent care dependent, and their overall care dependency does not
      differ (p = 0.56). Care dependency items with the lowest mean were mobility,
      hygiene, getting (un)dressed, continence, avoidance of danger and daily
      activities. Patients with CHF or COPD did not differ statistically significantly
      in those items. Only the items 'eating and drinking' almost achieved statistical
      significance (p = 0.06). CONCLUSION: Patients with CHF or COPD did not differ in
      levels of care dependency. Both patient populations are restricted in engaging in
      activities potentially associated with physical condition and possibly influenced
      by perceived dyspnoea. Furthermore, comorbidities like incontinence and cognitive
      impairment seem to play an important role regarding the degree of care
      dependency.

PMID- 24131294
TI  - The in-vitro antibacterial effects of organic salts, chemical disinfectants and
      antibiotics against pathogens of black disease in fairy shrimp of Thailand.
AB  - The antibacterial effects of organic salts, chemical disinfectants and
      antibiotics were evaluated on cultures of Aeromonas hydrophila C03, Aeromonas
      sobria C26, A. sobria C29, Aeromonas caviae C24 and Acinetobacter sp. SH-94B, the
      pathogens that cause black disease found in fairy shrimps (Streptocephalus
      sirindhornae Sanoamuang et al. (2000) and Branchinella thailandensis Sanoamuang,
      Saengphan & Murugan) of Thailand. The minimal inhibitory concentrations (MICs) of
      organic salts (sodium chloride and potassium chloride) and antibiotics
      (oxytetracycline dihydrate, streptomycin sulphate, kanamycin monosulphate,
      chloramphenicol and ampicillin) were determined using the agar-dilution method.
      The effect of chemical disinfectants (sodium hypochlorite and chlorine dioxide)
      was evaluated by exposing bacteria to different concentrations of these chemicals
      for different periods of time. Interestingly, all strains were intrinsically
      resistant to 0.25-3% sodium chloride and potassium chloride. The effect of sodium
      hypochlorite was greater than that of chlorine dioxide, and 5-20 MUg mL(-1) of
      sodium hypochlorite was sufficient to inhibit the growth of these bacteria, but
      the exposure time varied, depending on the bacterial species. Of the antibiotics
      tested, chloramphenicol and oxytetracycline dihydrate completely inhibited the
      selected strains. Chloramphenicol showed the highest antibacterial effect against
      all pathogenic species--the MIC and minimal bactericidal concentration (MBC)
      ranged from 0.8 to 3.1 MUg mL(-1) from 3.1 to 6.25 MUg mL(-1), respectively. To
      achieve control of black disease during cultivation of fairy shrimp, data derived
      from this study can be used as a basis for further toxicity tests in vivo.

PMID- 24131295
TI  - Pattern of intraocular pressure fluctuation in uveitic eyes treated with
      corticosteroids.
AB  - PURPOSE: To determine IOP fluctuation in uveitic eyes treated with
      corticosteroids. DESIGN: Prospective Observational Study. METHOD: Study of 116
      consecutive new uveitis patients visiting Uveitis clinic, BPKLCOS. IOP was
      meticulously monitored. Data was analyzed in SPSS-16 using paired samples 't
      test'. RESULTS: The mean IOP in all patients at presentation, at 1 week, 3 weeks
      and 6 weeks were respectively 14.66 mmHg, 14.72 mmHg, 14.75 mmHg and 14.93 mmHg.
      This progressive IOP rise was not statistically significant. Ocular hypertension
      was seen in 20% eyes; 64.5% were due to corticosteroids. Steroid-induced ocular
      hypertension was seen in 37.03% of oral group, 14.28% of posterior subtenon
      group, 8.57% of topical group. Antiglaucoma medications were started in 61.2% of
      the cases with raised IOP. None had to undergo glaucoma filtering surgery.
      CONCLUSION: Incidence of ocular hypertension in uveitic eyes was 20% in this
      study. Majority of them was corticosteroid induced. Timely medical treatment
      averted the necessity of surgical intervention for IOP control.

PMID- 24131296
TI  - Placental transfer of intravenous nicardipine and disposition into breast milk
      during the control of hypertension in women with pre-eclampsia.
AB  - OBJECTIVE: To assess nicardipine safety for fetuses and neonates. METHODS:
      Nicardipine was measured in maternal plasma (MP), umbilical cord arterial (UaP)
      and venous (UvP) plasma and breast milk (BrM) of 18 women with severe
      preeclampsia. RESULTS: Nicardipine was infused for a mean 11.9 +/- 10.5 days
      before and 4.6 +/- 1.6 days after delivery. Nicardipine dose and MP concentration
      were linearly correlated, as were MP with UaP, UvP, and BrM concentrations. The
      BrM/MP ratio was 0.06 to 0.30. The mean relative infant dose was 0.082%.
      CONCLUSION: Nicardipine is safe for fetuses and neonates due to its low levels of
      placental transfer and disposition in BrM.

PMID- 24131297
TI  - Stereotype threat can reduce older adults' memory errors.
AB  - Stereotype threat often incurs the cost of reducing the amount of information
      that older adults accurately recall. In the current research, we tested whether
      stereotype threat can also benefit memory. According to the regulatory focus
      account of stereotype threat, threat induces a prevention focus in which people
      become concerned with avoiding errors of commission and are sensitive to the
      presence or absence of losses within their environment. Because of this, we
      predicted that stereotype threat might reduce older adults' memory errors.
      Results were consistent with this prediction. Older adults under stereotype
      threat had lower intrusion rates during free-recall tests (Experiments 1 and 2).
      They also reduced their false alarms and adopted more conservative response
      criteria during a recognition test (Experiment 2). Thus, stereotype threat can
      decrease older adults' false memories, albeit at the cost of fewer veridical
      memories, as well. 

PMID- 24131298
TI  - A randomized study of computerized working memory training and effects on
      functioning in everyday life for patients with brain injury.
AB  - BACKGROUND: Working memory (WM) problems influence most activities of daily
      living. The aim was to evaluate if computerized working memory training after
      brain injury has a significant effect on functioning in daily life. METHOD:
      Outpatients with WM deficits, aged 22-63 years, were randomized to either
      intervention group (IG, n = 20) or control group (CG, n = 18) and received 5
      weeks standard rehabilitation. The IG also received WM training with the Cogmed
      QM training program. Assessments were made before (A1), immediately (A2) and 3
      months (A3) after intervention. After follow-up, the CG was offered the
      computerized training and assessed after this (A4; n = 8). Assessments included
      the WAIS-III Digit span reversed, Fatigue Impact Scale (FIS), Assessment of Motor
      and Process Skills (AMPS), Rivermead Behavioural Memory Test-II (RBMT-II) and a
      WM questionnaire. RESULTS: The IG improved on digit span and FIS, A1-A2, and
      significantly more than the CG on the WM questionnaire, A1-A3. Both groups
      improved in AMPS motor skill and the AMPS process skill score tended towards
      significant improvement in the IG, from A1-A3. After training (A3-A4), the CG
      improved in digit span and RBMT-II. CONCLUSION: The WM training seems to have a
      generalized effect on functional activity and lessens fatigue.

PMID- 24131299
TI  - Radiation channels close to a plasmonic nanowire visualized by back focal plane
      imaging.
AB  - We investigated the angular radiation patterns, a key characteristic of an
      emitting system, from individual silver nanowires decorated with rare earth ion
      doped nanocrystals. Back focal plane radiation patterns of the nanocrystal
      photoluminescence after local two-photon excitation can be described by two
      emission channels: excitation of propagating surface plasmons in the nanowire
      followed by leakage radiation and direct dipolar emission observed also in the
      absence of the nanowire. Theoretical modeling reproduces the observed radiation
      patterns which strongly depend on the position of excitation along the nanowire.
      Our analysis allows us to estimate the branching ratio into both emission
      channels and to determine the diameter-dependent surface plasmon quasi-momentum,
      important parameters of emitter-plasmon structures. 

PMID- 24131300
TI  - TOF-SIMS 3D imaging of native and non-native species within HeLa cells.
AB  - In this study, a non-native chemical species, bromodeoxyuridine (BrdU), was
      imaged within single HeLa cells using time-of-flight secondary ion mass
      spectrometry (TOF-SIMS). z-corrected 3D images were reconstructed that accurately
      portray the distribution of intracellular BrdU as well as other intracellular
      structures. The BrdU was localized to the nucleus of cells, whereas structures
      composed of CxHyOz(-) species were located in bundles on the periphery of cells.
      The CxHyOz(-) subcellular features had a spatial resolution at or slightly below
      a micrometer (900 nm), as defined by the distance between the 16% and 84%
      intensities in a line scan across the edge of the features. Additionally,
      important parameters influencing the quality of the HeLa cell 3D images were
      investigated. Atomic force microscopy measurements revealed that the HeLa cells
      were sputtered at a rate of approximately 4 nm per 10(13) C60(+) ions/cm(2) at 10
      keV and a 45 degrees  incident angle. Optimal 3D images were acquired using a
      Bi3(+) liquid metal ion gun operating in the simultaneous high mass and spatial
      resolution mode. 

PMID- 24131301
TI  - Faecal worm egg count analysis for targeting anthelmintic treatment in horses:
      points to consider.
AB  - Equine gastrointestinal nematodes are ubiquitous; in horses that graze
      contaminated pasture and that are not treated appropriately, large numbers of
      worms can accumulate, which can lead to serious clinical disease. Nematode
      control has traditionally followed interval treatment regimens, which involve
      regular anthelmintic administration to all horses based on the strongyle egg
      reappearance periods of each drug, usually defined around the time of licensing.
      Interval treatment programmes have resulted in substantial reductions in large
      strongyle disease, but have made major contributions to the development of
      anthelmintic resistance, particularly in cyathostomins. Cyathostomin resistance
      to 2 of the 3 available anthelmintic classes is widespread, and resistance to
      both classes in single populations is not uncommon. Reduced efficacy of the most
      commonly used macrocyclic lactone anthelmintics, as measured by shortened egg
      reappearance periods after treatment, is emerging in cyathostomins. Macrocyclic
      lactone resistance is also now commonly reported in Parascaris equorum on stud
      farms. Faecal worm egg counts (FWEC) are increasingly being used as part of
      targeted approaches to parasite control, whereby only those horses with moderate
      to high FWEC within a group are treated with an anthelmintic. The objective of
      this approach is to reduce environmental contamination, while leaving a
      proportion of the worm population in some horses unexposed to selection pressure
      for anthelmintic resistance. This article reviews recent findings in equine
      parasitology research that will underpin guidelines for control, with a
      particular focus on how to optimise the value of FWEC methodologies and
      anthelmintic efficacy analyses. 

PMID- 24131302
TI  - Detection of two highly stable silicon nitrides: HSiNSi and H3SiNSi.
AB  - The formation mechanisms of silicon nitride and silicon nitrogen hydrogen films,
      both produced by chemical vapor deposition (CVD) techniques and widely used in
      electronic device fabrication, are poorly understood. Identification of gas-phase
      intermediates formed from starting materials, typically silane, ammonia, and/or
      nitrogen, is a critical step in assessing the interplay between gas and surface
      processes in film formation. Two potential intermediates in this process, HSiNSi
      and H3SiNSi, have now been detected in a molecular beam by means of rotational
      spectroscopy. Both molecules were produced in electrical discharges of CVD-like
      gas mixtures and are the most readily observed silicon-nitrogen-containing
      molecules in the 6-20 GHz frequency range, though neither has been the subject of
      prior experimental or theoretical studies. HSiNSi and H3SiNSi are likely formed
      from reactions involving the silanitrile radical (SiN, isoelectronic to CN),
      implying that similar gas-phase reactions may be involved in film growth. 

PMID- 24131303
TI  - Laser-capture dissection and immunohistochemistry reveals chloride and mucous
      cell specific gene expression in gills of seawater acclimated Atlantic salmon
      Salmo salar.
AB  - Laser-capture microdissection and immunohistochemistry were used to show that
      gene and protein expression varied in different cell types in the gills of
      Atlantic salmon Salmo salar, with chloride cells found to express high levels of
      sodium potassium ATPase and mucous cells expressing elevated levels of anterior
      gradient protein. It is therefore important that studies of gene expression in
      gill tissue take account of the proportion of the various cell types present. 

PMID- 24131305
TI  - Influence of preformed donor-specific antibodies and C4d on early liver allograft
      function.
AB  - INTRODUCTION. The impact of preformed donor-specific antibodies (DSA) is
      incompletely understood in liver transplantation. The incidence and impact of
      preformed DSA on early post liver transplant were assessed and these were
      correlated with compliment fragment C4d on allograft biopsy. METHODS.
      Pretransplant serum from 41 consecutive liver transplant recipients (brain dead
      donors; DBD = 27 and cardiac death donors; DCD = 14) were tested for class
      specific anti-human leukocyte antigen (HLA) and compared against donor HLA types.
      Liver biopsies were taken during cold storage (t-1) and post-reperfusion (t0)
      stained with C4d and graded for preservation-reperfusion injury (PRI). RESULTS.
      Of the 41 recipients, 8 (20%) had anti-HLA class I/II antibodies pretransplant, 3
      (7%) were confirmed preformed DSA; classes I and II (n=1) and class I only (n=2).
      No biopsies showed definite evidence of antibody-mediated rejection. Graft
      biopsies in overall showed only mild PRI with ischemic hepatocyte C4d pattern
      similar in both positive and negative DSA patients. One DSA-positive (33%)
      compared with four DSA-negative patients (10%) had significant early graft
      dysfunction; severe PRI causing graft loss from primary nonfunction was seen only
      in DSA-negative group. Allograft biopsy of preformed DSA-positive patient
      demonstrated only minimal PRI; however, no identifiable cause could be attributed
      to graft dysfunction other than preformed DSA. CONCLUSION. Preformed DSA are
      present in 5-10% liver transplant recipients. There is no association between
      anti-HLA DSA and PRI and C4d, but preformed DSA may cause early morbidity. Larger
      studies on the impact of DSA with optimization of C4d techniques are required.

PMID- 24131304
TI  - The effects of lebrikizumab in patients with mild asthma following whole lung
      allergen challenge.
AB  - BACKGROUND: Interleukin 13 (IL13) is a T-helper type 2 (Th2) cytokine associated
      with inflammation and pathology in allergic diseases such as bronchial asthma. We
      have shown that treatment with lebrikizumab, an anti-IL13 monoclonal antibody,
      significantly improves prebronchodilator forced expiratory volume in 1 s (FEV(1))
      in a subset of subjects with uncontrolled asthma. OBJECTIVE: To evaluate efficacy
      and safety of lebrikizumab in subjects with mild asthma who underwent bronchial
      allergen challenge. METHODS: Twenty-nine subjects were randomized 1 : 1-5 mg/kg
      lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4
      weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late
      asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1
      measured 2-8 h following inhaled allergen challenge. Serum biomarkers were
      measured to verify IL13 pathway inhibition and identify patients with an
      increased response to lebrikizumab. RESULTS: At Week 13, the LAR in lebrikizumab
      subjects was reduced by 48% compared with placebo subjects, although this was not
      statistically significant (95% confidence interval, -19%, 90%). Exploratory
      analysis indicated that lebrikizumab-treated subjects with elevated baseline
      levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a
      greater reduction in LAR compared with subjects with lower baseline levels of
      these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2
      inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17
      by approximately 25% (P < 0.01). Lebrikizumab was well tolerated. CONCLUSION AND
      CLINICAL RELEVANCE: Lebrikizumab reduced the LAR in subjects with mild asthma.
      Clinical trial number NCT00781443.

PMID- 24131306
TI  - When should FDG-PET be used in the modern management of lymphoma?
AB  - Positron Emission Tomography (PET) is a functional imaging technique that,
      combined with computerized tomography (PET-CT), is increasingly used in lymphoma.
      Most subtypes accumulate fluorodeoxyglucose (FDG) and the increased sensitivity
      of PET-CT, especially for extranodal disease, compared to CT, makes PET-CT an
      attractive staging tool. The availability of a staging PET-CT scan also improves
      the accuracy of subsequent response assessment. 'Interim' PET-CT can be used to
      assess early response and end-of-treatment PET-CT assesses remission. Clinical
      trials are currently seeking to establish whether the predictive value of PET-CT
      can be successfully used to guide individual treatment to reduce toxicity and/or
      to improve outcomes. Standardized methods for performing and reporting PET have
      been developed in the context of trials. The role of PET in transplantation
      selection is currently evolving, as it appears to be more accurate and prognostic
      than CT. The role of FDG PET-CT throughout the management course in patients with
      lymphoma is explored in this review, with areas discussed that may limit the use
      of PET-CT imaging which clinicians should be familiar with to inform practice. 

PMID- 24131307
TI  - Nanofiber-based in vitro system for high myogenic differentiation of human
      embryonic stem cells.
AB  - Myogenic progenitor cells derived from human embryonic stem cells (hESCs) can
      provide unlimited sources of cells in muscle regeneration but their clinical uses
      are largely hindered by the lack of efficient methods to induce differentiation
      of stem cells into myogenic cells. We present a novel approach to effectively
      enhance myogenic differentiation of human embryonic stem cells using aligned
      chitosan-polycaprolactone (C-PCL) nanofibers constructed to resemble the
      microenvironment of the native muscle extracellular matrix (ECM) in concert with
      Wnt3a protein. The myogenic differentiation was assessed by cell morphology, gene
      activities, and protein expression. hESCs grown on C-PCL uniaxially aligned
      nanofibers in media containing Wnt3a displayed an elongated morphology uniformly
      aligned in the direction of fiber orientation, with increased expressions of
      marker genes and proteins associated with myogenic differentiation as compared to
      control substrates. The combination of Wnt3a signaling and aligned C-PCL
      nanofibers resulted in high percentages of myogenic-protein expressing cells over
      total treated hESCs (83% My5, 91% Myf6, 83% myogenin, and 63% MHC) after 2 days
      of cell culture. Significantly, this unprecedented high-level and fast myogenic
      differentiation of hESC was demonstrated in a culture medium containing no feeder
      cells. This study suggests that chitosan-based aligned nanofibers combined with
      Wnt3a can potentially act as a model system for embryonic myogenesis and muscle
      regeneration.

PMID- 24131308
TI  - Challenges in interpreting allergen microarrays in relation to clinical symptoms:
      a machine learning approach.
AB  - BACKGROUND: Identifying different patterns of allergens and understanding their
      predictive ability in relation to asthma and other allergic diseases is crucial
      for the design of personalized diagnostic tools. METHODS: Allergen-IgE screening
      using ImmunoCAP ISAC((r)) assay was performed at age 11 yrs in children
      participating a population-based birth cohort. Logistic regression (LR) and
      nonlinear statistical learning models, including random forests (RF) and Bayesian
      networks (BN), coupled with feature selection approaches, were used to identify
      patterns of allergen responses associated with asthma, rhino-conjunctivitis,
      wheeze, eczema and airway hyper-reactivity (AHR, positive methacholine
      challenge). Sensitivity/specificity and area under the receiver operating
      characteristic (AUROC) were used to assess model performance via repeated
      validation. RESULTS: Serum sample for IgE measurement was obtained from 461 of
      822 (56.1%) participants. Two hundred and thirty-eight of 461 (51.6%) children
      had at least one of 112 allergen components IgE > 0 ISU. The binary threshold
      >0.3 ISU performed less well than using continuous IgE values, discretizing data
      or using other data transformations, but not significantly (p = 0.1). With the
      exception of eczema (AUROC~0.5), LR, RF and BN achieved comparable AUROC, ranging
      from 0.76 to 0.82. Dust mite, pollens and pet allergens were highly associated
      with asthma, whilst pollens and dust mite with rhino-conjunctivitis. Egg/bovine
      allergens were associated with eczema. CONCLUSIONS: After validation, LR, RF and
      BN demonstrated reasonable discrimination ability for asthma, rhino
      conjunctivitis, wheeze and AHR, but not for eczema. However, further improvements
      in threshold ascertainment and/or value transformation for different components,
      and better interpretation algorithms are needed to fully capitalize on the
      potential of the technology.

PMID- 24131309
TI  - Polypharmacy and drug omissions across hospices in Northern Ireland.
AB  - BACKGROUND: Polypharmacy and drug omissions (DO) (i.e., drugs prescribed but not
      administered) may impact on quality of life of hospice inpatients. AIM: The
      study's objective was to assess for polypharmacy and DO across hospice inpatient
      units in Northern Ireland (NI). DESIGN: A retrospective chart review of
      consecutive admissions to five adult hospices in NI in 2011-2012 was performed.
      Only regularly prescribed oral and nebulized medications were analyzed. RESULTS:
      Inpatient admissions (n=138) were reviewed (58% male, median age 68, 91% had
      cancer). The average number of regularly prescribed medications was eight (range
      0-17) on admission, 10 (1-21) at discharge, and two (0-15) at time of death. Of
      all prescribed doses, 8.8% were omitted. The most frequent DOs were laxatives
      (38%), mouth care (11%), and mineral supplements (9%). Reasons for DO included
      patient refusal (46%), patient asleep or drowsy (20%), and drug not available
      (7%). DOs numbering 197 lasted 24 to 72 hours. No action was taken by medical
      staff for 79% of these. DOs numbering 85 lasted over 72 hours. While fewer drug
      doses were prescribed for patients who died during admission, the proportion of
      DO was higher (12.4%) than for those discharged (6.9%). DO increased in the last
      week of life (23%). CONCLUSIONS: Polypharmacy is prevalent among hospice
      inpatients. Drugs omitted amounted to 8.8%, with the frequency of DO increasing
      in those who were dying. Documentation justifying DO was lacking. Daily focused
      drug chart review, pharmacy support, and electronic prescribing may all help to
      reduce and rationalize medication burden and aid prompt and effective management
      of DO.

PMID- 24131310
TI  - Lysophosphatidic acid protects human mesenchymal stromal cells from
      differentiation-dependent vulnerability to apoptosis.
AB  - The survival of transplanted cells and their resulting efficacy in cell-based
      therapies is markedly impaired due to serum deprivation and hypoxia (SD/H)
      resulting from poor vascularization within tissue defects. Lysophosphatidic acid
      (LPA) is a platelet-derived growth factor with pleiotropic effects on many cell
      types. Mesenchymal stromal cells (MSC) exhibit unique secretory and stimulatory
      characteristics depending on their differentiation state. In light of the
      potential of MSC in cell-based therapies, we examined the ability of LPA to
      abrogate SD/H-induced apoptosis in human MSC at increasing stages of osteogenic
      differentiation in vitro and assessed MSC survival in vivo. Undifferentiated MSC
      were rescued from SD/H-induced apoptosis by treatment with both 25 and 100 MUM
      LPA. However, MSC conditioned with osteogenic supplements responded to 25 MUM
      LPA, and cells conditioned with dexamethasone-containing osteogenic media
      required 100 MUM LPA. This rescue was mediated through LPA1 in all cases. The
      addition of 25 MUM LPA enhanced vascular endothelial growth factor (VEGF)
      secretion by MSC in all conditions, but VEGF availability was not responsible for
      protection against apoptosis. We also showed that codelivery of 25 MUM LPA with
      MSC in alginate hydrogels significantly improved the persistence of
      undifferentiated MSC in vivo over 4 weeks as measured by bioluminescence imaging.
      Osteogenic differentiation alone was protective of SD/H-induced apoptosis in
      vitro, and the synergistic delivery of LPA did not enhance persistence of
      osteogenically induced MSC in vivo. These data demonstrate that the capacity of
      LPA to inhibit SD/H-induced apoptosis in MSC is dependent on both the
      differentiation state and dosage. This information will be valuable for
      optimizing osteogenic conditioning regimens for MSC before in vivo
      implementation.

PMID- 24131311
TI  - Prevalence of Toxoplasma gondii and Toxocara canis among Patients with Uveitis.
AB  - PURPOSE: To investigate the prevalence of Toxoplasma gondii and Toxocara canis in
      patients with uveitis. METHODS: Patients with uveitis were examined. Serum
      antibodies to T. gondii and T. canis were tested by using the enzyme-linked
      immunosorbent assay. Polymerase chain reaction (PCR) was done using blood and
      aqueous humor (AH). RESULTS: Ninety-eight patients were enrolled. Mean age was
      43.5 +/- 13.2 years. Six patients were seropositive for T. gondii with the
      following pattern: anterior uveitis, 1; posterior uveitis with retinitis, 2; pan
      uveitis, 2. One patient had a positive PCR result for T. gondii in AH, who showed
      panuveitis. Twenty-three patients were positive to serum IgG for T. canis with
      the following clinical manifestation: granuloma, 6; pigmented scar, 3; vitritis,
      6--but none were PCR positive. CONCLUSIONS: T. gondii and T. canis are still
      important causes of uveitis. Ocular toxocariasis is not an uncommon cause of
      uveitis, even in adults.

PMID- 24131312
TI  - Revealing bismuth oxide hollow nanoparticle formation by the Kirkendall effect.
AB  - We study the formation of bismuth oxide hollow nanoparticles by the Kirkendall
      effect using liquid cell transmission electron microscopy (TEM). Rich dynamics of
      bismuth diffusion through the bismuth oxide shell have been captured in situ. The
      diffusion coefficient of bismuth through bismuth oxide shell is 3-4 orders of
      magnitude higher than that of bulk. Observation reveals that defects,
      temperature, sizes of the particles, and so forth can affect the diffusion of
      reactive species and modify the kinetics of the hollowing process. 

PMID- 24131313
TI  - Facing the block and false positives in Mohs surgery: a retrospective study of
      2,198 cases.
AB  - BACKGROUND: "Facing the block" is defined as trimming tissue on a microtome from
      peripheral or deep surgical margins before sectioning. Facing includes trimming
      performed intentionally but unnecessarily, accidentally, or out of necessity
      because of one's choice of embedding and freezing method. OBJECTIVE: To assess
      whether facing the block is associated with a greater number of stages to clear
      tumor and, by inference, a significant false positive rate. MATERIALS AND
      METHODS: A retrospective analysis was performed comparing the average number of
      stages per Mohs case at two surgical facilities with the same physician over a 1
      year period. Site A histotechnologists intentionally face the block, whereas site
      B histotechnologists do not. Tissue thickness lost during trimming at each site
      was recorded for 4 weeks. RESULTS: Comparing Sites A and B, stages per case were
      1.92 and 1.53, respectively (p < .01) and trimming depths before the first
      section were 325 and 187 MUm (p < .01). CONCLUSION: Facing the block is
      associated with 0.39 more stages per case and, by inference, a false-positive
      rate of approximately 39%. Mohs surgeons should evaluate the methods of tissue
      preparation that their histotechnologists use. Facing the block should not be
      performed.

PMID- 24131314
TI  - Return to work after traumatic brain injury: Systematic review.
AB  - OBJECTIVE: To evaluate the evidence on pre- and post-injury predictors of
      vocational outcome after traumatic brain injury (TBI). LITERATURE SELECTION AND
      CRITICAL ANALYSIS: The search was conducted on PubMed and Central databases since
      1990. A clinical question was formulated according to the PICO framework.
      Clinical relevance of the selected studies was evaluated following the GRADE
      framework. MAIN OUTCOMES AND RESULTS: The main outcome measures were employment
      status and return to work after TBI. Methodological quality of most of the
      relevant 12 controlled and 68 uncontrolled studies included in the review was
      estimated as very low. There was weak evidence that age, educational level, pre-
      and post-injury occupational status, severity of TBI, functional status, level of
      depression and anxiety, gender and race may be predictive for the vocational
      outcome after TBI. CONCLUSIONS AND IMPLICATIONS FOR FURTHER RESEARCH: No strong
      evidence was found that vocational outcomes after TBI could be predicted or
      improved. There is a need for both experimental and observational well-conducted
      studies on this important subject. Researchers are strongly encouraged to use
      unified and standardized terms and scales in further studies. The authors suggest
      the International Classification of Functioning, Disability and Health (ICF) as
      the best tool available for this purpose.

PMID- 24131315
TI  - Density-dependent onset of the long-range exchange: a key to donor-acceptor
      properties.
AB  - Quantum mechanical methods based on the density functional theory (DFT) offer a
      realistic possibility of first-principles design of organic donor-acceptor
      systems and engineered band gap materials. This promise is contingent upon the
      ability of DFT to predict one-particle states accurately. Unfortunately,
      approximate functionals fail to align the orbital energies with ionization
      potentials. We describe a new paradigm for achieving this alignment. In the
      proposed model, an average electron-exchange hole separation controls the onset
      of the orbital-dependent exchange in approximate range-separated functionals. The
      correct description of one-particle states is thus achieved without explicit
      electron removal or attachment. Extensive numerical tests show that the proposed
      method provides physically sound orbital gaps and leads to excellent predictions
      of charge-transfer excitations and other properties critically depending on the
      tail of the electron density. 

PMID- 24131316
TI  - Associations compete directly in memory.
AB  - Associations are confusable when they share an item. For example, double-function
      pairs (with the form AB, BC) are harder to remember than control pairs. Although
      ambiguous pairs are more difficult on average, it is not clear whether memories
      for associations compete directly with one another (associative competition
      hypothesis), as assumed by models that incorporate associative symmetry
      (bidirectional associations). Alternatively, associative interference results
      might be explained away by: (a) item suppression hypothesis: competition only
      between memory for the two target items (A and C are both targets of B); (b)
      candidate competition hypothesis: The cue (B) retrieves two potential targets, A
      and C, which compete to be output. These alternative hypotheses could explain
      previous results in the related, AB/AC learning procedure. Our procedure included
      a large amount of interference that had to be resolved within a single study set.
      Participants studied sets of control (single-function) and double-function pairs
      and were asked to produce one or two associates, respectively, to cue items.
      Recall of AB and BC were negatively correlated and could not be explained away by
      item suppression or competition between simultaneously retrieved candidate items.
      Thus, competition can occur at the level of representation of associations,
      regardless of which item is the cue, consistent with associative symmetry. 

PMID- 24131317
TI  - Physics of heat generation using magnetic nanoparticles for hyperthermia.
AB  - Magnetic nanoparticle hyperthermia and thermal ablation have been actively
      studied experimentally and theoretically. In this review, we provide a summary of
      the literature describing the properties of nanometer-scale magnetic materials
      suspended in biocompatible fluids and their interactions with external magnetic
      fields. Summarised are the properties and mechanisms understood to be responsible
      for magnetic heating, and the models developed to understand the behaviour of
      single-domain magnets exposed to alternating magnetic fields. Linear response
      theory and its assumptions have provided a useful beginning point; however, its
      limitations are apparent when nanoparticle heating is measured over a wide range
      of magnetic fields. Well-developed models (e.g. for magnetisation reversal
      mechanisms and pseudo-single domain formation) available from other fields of
      research are explored. Some of the methods described include effects of moment
      relaxation, anisotropy, nanoparticle and moment rotation mechanisms, interactions
      and collective behaviour, which have been experimentally identified to be
      important. Here, we will discuss the implicit assumptions underlying these
      analytical models and their relevance to experiments. Numerical simulations will
      be discussed as an alternative to these simple analytical models, including their
      applicability to experimental data. Finally, guidelines for the design of optimal
      magnetic nanoparticles will be presented.

PMID- 24131318
TI  - Antimetastatic effects of alpha-carotene and possible mechanisms of action in
      human hepatocarcinoma SK-Hep-1 cells.
AB  - In vitro evidence suggests that alpha-carotene (AC) is an antimetastatic agent
      against cancer cells, but the mechanistic action is unclear. This study
      investigated the antimetastatic effect and possible mechanism of AC in comparison
      with beta-carotene (BC) using human hepatocarcinoma SK-Hep-1 cells. Results
      reveal that treatment with AC (0.5-2.5 MUM) for 48 h significantly inhibited
      invasion, migration, and adhesion of SK-Hep-1 cells in a concentration-dependent
      manner. These effects of AC were stronger than those of BC at the same
      concentration (2.5 MUM). Mechanistically, AC significantly decreased activities
      of urokinase plasminogen activator and matrix metalloproteinases (MMP)-2 and -9,
      but increased protein expression of plasminogen activator inhibitor-1, tissue
      inhibitor of MMP (TIMP)-1 and -2, and nm23-H1, an antimetastatic protein. AC also
      attenuated focal adhesion kinase-mediated phosphorylation of mitogen-activated
      protein kinase family resulting in decreased protein expression of Rho and Rac 1.
      Overall, these data suggest that AC has potential as an antimetastatic agent. 

PMID- 24131319
TI  - Is MC1 dispensable for regulation of cutaneous inflammatory and immune responses?
AB  - The melanocortin-1 receptor (MC1 ) - being most abundantly expressed in the skin
      by melanocytes - has a physiological role for melanin pigmentation in many
      vertebrate species. MC1 has also been implicated in regulation of skin
      inflammation as this receptor is detectable in the majority of non-melanocytic
      cell types and its ligand alpha-melanocyte-stimulating hormone (alpha-MSH) exerts
      immunoregulatory and anti-inflammatory effects. However, in vivo studies on mice
      with targeted disruption of MC1 have been missing in the context of skin
      inflammation until recently. Wolnicka-Glubisz et al. now reported that the course
      of ultraviolet (UV)-induced inflammation, contact hypersensitivity, neonatal
      immune tolerance and UV-induced immunosuppression is similar in MC1 signal
      deficient (C57BL/6-Mc1r(e/e)) and wild-type mice. These unexpected findings are
      supported by own observations in experimentally induced immune-complex-mediated
      vasculitis: Mc1r(e/e) mice exhibited a similar extent of the reverse passive
      cutaneous Arthus reaction compared with wild-type animals. Future studies are
      thus needed to clarify whether these findings are due to limitations in the
      chosen mouse model and/or point to additional MC subtypes that may regulate
      inflammatory and immune responses in the skin.

PMID- 24131320
TI  - Calcium plus vitamin D supplementation and health outcomes five years after
      active intervention ended: the Women's Health Initiative.
AB  - BACKGROUND: Clinical outcomes of the Women's Health Initiative (WHI) calcium plus
      vitamin D supplementation trial have been reported during 7.0 years of active
      intervention. We now report outcomes 4.9 years after the intervention stopped and
      cumulative findings. METHODS: Postmenopausal women (N=36,282) were randomized;
      postintervention follow-up continued among 29,862 (86%) of surviving
      participants. Primary outcomes were hip fracture and colorectal cancer. Breast
      cancer, all cancers, cardiovascular disease (CVD), and total mortality were
      predetermined major study outcomes. RESULTS: Hip fracture incidence was
      comparable in the supplement and the placebo groups, postintervention hazard
      ratio (HR)=0.95, 95% confidence interval (95% CI: 0.78, 1.15) and overall HR=0.91
      (95% CI: 0.79, 1.05). Overall, colorectal cancer incidence did not differ between
      randomization groups, HR=0.95 (95% CI: 0.80, 1.13). Throughout, there also was no
      difference in invasive breast cancer, CVD, and all-cause mortality between
      groups. In subgroup analyses, the invasive breast cancer effect varied by
      baseline vitamin D intake (p=0.03 for interaction). Women with vitamin D intakes
      >600 IU/d, had an increased risk of invasive breast cancer, HR=1.28 (95% CI;
      1.03, 1.60). Over the entire study period, in post hoc analyses, the incidence of
      vertebral fractures, HR=0.87 (95% CI: 0.76, 0.98) and in situ breast cancers,
      HR=0.82 (95% CI: 0.68, 0.99) were lower among women randomized to
      supplementation. CONCLUSION: After an average of 11 years, calcium and vitamin D
      supplementation did not decrease hip fracture or colorectal cancer incidence.
      Exploratory analyses found lower vertebral fracture and in situ breast cancer
      incidence in the supplement users. There was no effect on CVD or all-cause
      mortality.

PMID- 24131322
TI  - Colonic J-pouch versus Baker type for rectal reconstruction after anterior
      resection of rectal cancer.
AB  - OBJECTIVE. There is no consensus regarding reconstruction type after anterior
      resection for rectal cancer. We conducted a meta-analysis of relevant randomized
      controlled trials (RCTs) to compare outcomes of colonic J-pouch (CJlP) and side
      to-end anastomosis (STEA) after anterior resection of rectal cancer. METHODS.
      Electronic databases were searched in January 2013, with six RCTs selected for
      further analysis, for a total of 451 patients (229 CJP, 222STEA). Outcome
      measures included surgical, physiologic, and functional outcomes, as well as
      postoperative complications. The odds ratio (OR) was used in the statistical
      analysis; in other circumstances, qualitative descriptions were performed.
      RESULTS. As far as surgical outcomes and postoperative complications, there was
      no difference between groups. While functional outcomes were substantially
      impaired, this was similar between groups. CJP demonstrated better function in
      the early postoperative period. No difference was seen between groups with
      regards to physiologic outcome. CONCLUSION. CJP and STEA are comparable when
      choosing the type of reconstruction for restoration of bowel continuity in
      anterior resection for rectal cancer.

PMID- 24131321
TI  - Maternal depression mediates the association between intimate partner violence
      and food insecurity.
AB  - BACKGROUND: Examination of maternal experiences of intimate partner violence
      (IPV) and depression as risk factors for food insecurity can provide a more
      nuanced understanding of the role that the family environment and women's health
      plays in the lives of families with young children that experience food
      insecurity. We investigated the longitudinal association between mothers'
      experiences of IPV and household food insecurity, and whether maternal depression
      mediated the relationship. METHODS: IPV, depression, and food insecurity were
      assessed among 1,690 socioeconomically disadvantaged mothers of young children
      who participated in the Fragile Families and Child Wellbeing study. Longitudinal
      multivariate logistic regression models were used to examine the association
      between IPV measured 3 years after the child's birth and increase in food
      insecurity from child's third to fifth birthday, as well as the mediating role of
      maternal depression, controlling for a number of maternal and household
      characteristics. RESULTS: Mothers who reside in food insecure households and
      those who experience IPV share similar characteristics of socioeconomic
      disadvantage and a greater propensity for depression compared to their
      counterparts. Mothers' experiences of IPV predicted an increased risk of
      household food insecurity two years later, and the relationship was mediated by
      maternal depression. CONCLUSIONS: Food insecure mothers may benefit from
      widespread assistance. Targeting issues central to women's health must become a
      priority in combating food insecurity. Having IPV and mental health screenings
      coincide with food assistance applications may help identify women who would
      benefit from resources designed to increase physical safety, psychological well
      being, and food security.

PMID- 24131323
TI  - Molecular excitation in the interstellar medium: recent advances in collisional,
      radiative, and chemical processes.

PMID- 24131324
TI  - Clinical features and presentation of posterior scleritis: a report of 31 cases.
AB  - PURPOSE: To describe clinical features, ocular complications, and visual outcomes
      of patients with posterior scleritis. METHODS: Clinical characteristics of a
      subset of 31 patients with posterior scleritis were studied and compared with 469
      patients with anterior scleritis. RESULTS: Of 500 patients, 31 (6.2%) had
      posterior scleritis. Most patients presented with subacute (80.6%), unilateral
      (61.3%) scleral inflammation. Pain was moderate to severe in 54.8% of patients.
      Concomitant anterior scleritis was observed during follow-up in 77.4% of patients
      and in all patients with moderate to severe pain. Patients with posterior
      scleritis were significantly younger (43.6 vs. 54.4 years, p < 0.001) and had
      significantly higher decrease of vision (29.0 vs. 14.9%, p = 0.027) than those
      with isolated anterior scleritis. CONCLUSIONS: Posterior scleritis must be
      considered in patients with decrease of vision, mild to severe pain, optic disc
      edema, and/or posterior uveitis. Moderate to severe pain may be associated with
      poorer visual outcome.

PMID- 24131325
TI  - Combined NMR and GC-MS analyses revealed dynamic metabolic changes associated
      with the carrageenan-induced rat pleurisy.
AB  - Inflammation is closely associated with pathogenesis of various metabolic
      disorders, cardiovascular diseases, and cancers. To understand the systems
      responses to localized inflammation, we analyzed the dynamic metabolic changes in
      rat plasma and urine associated with the carrageenan-induced self-limiting
      pleurisy using NMR spectroscopy in conjunction with multivariate data analysis.
      Fatty acids in plasma were also analyzed using GC-FID/MS with the data from
      clinical chemistry and histopathology as complementary information. We found that
      in the acute phase of inflammation rats with pleurisy had significantly lower
      levels in serum albumin, fatty acids, and lipoproteins but higher globulin level
      and larger quantity of pleural exudate than controls. The carrageenan-induced
      inflammation was accompanied by significant metabolic alterations involving TCA
      cycle, glycolysis, biosyntheses of acute phase proteins, and metabolisms of amino
      acids, fatty acids, ketone bodies, and choline in acute phase. The resolution
      process of pleurisy was heterogeneous, and two subgroups were observed for the
      inflammatory rats at day-6 post treatment with different metabolic features
      together with the quantity of pleural exudate and weights of thymus and spleen.
      The metabolic differences between these subgroups were reflected in the levels of
      albumin and acute-phase proteins, the degree of returning to normality for
      multiple metabolic pathways including glycolysis, TCA cycle, gut microbiota
      functions, and metabolisms of lipids, choline and vitamin B3. These findings
      provided some essential details for the dynamic metabolic changes associated with
      the carrageenan-induced self-limiting inflammation and demonstrated the combined
      NMR and GC-FID/MS analysis as a powerful approach for understanding biochemical
      aspects of inflammation. 

PMID- 24131326
TI  - Bendamustine plus alemtuzumab is safe and feasible treatment for fludarabine
      refractory chronic lymphocytic leukaemia (CLL).

PMID- 24131327
TI  - Fatalities involving acetaminophen combination products reported to United States
      poison centers.
AB  - CONTEXT: Deaths from overdose of acetaminophen (APAP) combination medications are
      reported, yet the individual ingredients are not well examined as individual
      putative causes of death. OBJECTIVE: To examine the individual contribution of
      APAP or other ingredient(s) to fatalities resulting from ingestion of APAP
      combination products reported to poison centers. MATERIALS AND METHODS: A search
      in the United States (US) National Poison Data System between 1 January 2000 and
      31 December 2009 (10 years) was conducted. Only fatal cases determined by
      American Association of Poison Control Centers Fatality Review team to be caused
      by ingestion of one or more APAP combination products were included. The fatality
      abstract narrative for each case was obtained. Each narrative abstract was rated
      independently by four reviewers and putative cause of death was determined to be
      APAP, 'other ingredient' or 'unable to determine'. Fleiss' Kappa test was
      utilized to assess interrater agreement. RESULTS: Three hundred and thirty-seven
      deaths met inclusion criteria: 204 were due to suicides, 96 were the result of
      nonmedical use, 3 were from a therapeutic error, 1 resulted from an unsupervised
      pediatric ingestion, and 33 were due to unknown reason for exposure. The overall
      putative cause of death was APAP in 60.8%, other ingredients in 29.7%, and unable
      to determine in 9.5% of fatalities. APAP was responsible for the fatality in
      79.2% of deaths resulting from nonmedical use of APAP combination products.
      Fleiss Kappa was 0.74, indicating substantial interrater agreement. DISCUSSION
      AND CONCLUSION: The most common putative cause of death in fatal overdoses
      involving APAP combination products reported to US poison centers is the APAP
      component.

PMID- 24131328
TI  - Delayed bupropion cardiotoxicity associated with elevated serum concentrations of
      bupropion but not hydroxybupropion.
AB  - CONTEXT: Bupropion overdose commonly causes generalized seizures and central
      nervous system depression. Less commonly, cardiotoxicity has been reported. The
      toxicity of the parent drug compared to its active metabolite hydroxybupropion is
      uncertain. CASE DETAILS: A 31-year-old man presented to the emergency department
      with altered mental status after an intentional overdose of bupropion. Three
      hours after admission he developed status epilepticus requiring intubation, and
      13 h after admission he developed marked widening of the QRS complex and
      prolongation of the QTc interval. Serial serum bupropion levels peaked with the
      onset of cardiotoxicity (334 ng/mL) and fell into the therapeutic range within 24
      h, which coincided with normalization of his ECG intervals. Levels of the
      metabolite hydroxybupropion peaked later (4302 ng/mL) and remained elevated even
      after neurological and cardiotoxic symptoms resolved. DISCUSSION: Cardiotoxicity
      appears to be caused primarily by bupropion rather than its active metabolite
      hydroxybupropion.

PMID- 24131329
TI  - Dynamic high-resolution ultrasound in vivo imaging of hyaluronic acid filler
      injection.
AB  - BACKGROUND: High-resolution ultrasound (HRU) imaging is a useful tool to study
      hyaluronic acid (HA) filler injected in the face. OBJECTIVE: To observe real-time
      injection of HA using HRU and describe behavior of the gel injection in various
      anatomic layers and the effect of massage. METHODS: Deep (preperiosteal),
      intermediate (subdermal), and superficial (dermal) injections of HA were
      performed in the supraclavicular area under ultrasonography visualization on a
      healthy volunteer. Videos were obtained during injection and static images at
      several time points, including during injection, immediately after injection, 5
      minutes after massage of the treated area, and at 2 weeks after injection.
      RESULTS: During injection, dermally injected HA stayed within the dermis,
      increasing its echogenicity; subdermally injected HA formed multiple anechoic
      pearls; and preperiosteal HA produced a single anechoic bubble with diffuse
      margins. No vertical transection of the planes was observed during injection or
      after massage. Two-week postinjection imaging showed persistence of the varying
      HA morphology in each plane. CONCLUSIONS: High-resolution ultrasound allows in
      vivo study of HA injection behavior. HA adopts different morphology within the
      tissue depending on the density and compliance of the tissues in the plane of
      injection.

PMID- 24131331
TI  - Does underwater flash photography affect the behaviour, movement and site
      persistence of seahorses?
AB  - The effect of flash photography on seahorse species has never been tested. An
      experiment was established to test the effect of flash photography and the
      handling of Hippocampus whitei, a medium-sized seahorse species endemic to
      Australia, on their behavioural responses, movements and site persistence. A
      total of 24 H. whitei were utilized in the experiment with eight in each of the
      three treatments (flash photography, handling and control). The effect of
      underwater flash photography on H. whitei movements was not significant; however,
      the effect of handling H. whitei to take a photograph had a significant effect on
      their short-term behavioural responses to the photographer. Kaplan-Meier log-rank
      test revealed that there was no significant difference in site persistence of H.
      whitei from each of the three treatments and that flash photography had no long
      term effects on their site persistence. It is concluded that the use of flash
      photography by divers is a safe and viable technique with H. whitei, particularly
      if photographs can be used for individual identification purposes. 

PMID- 24131330
TI  - Determining carbapenemase activity with 18O labeling and targeted mass
      spectrometry.
AB  - Carbapenems are broad spectrum antibiotics considered as a "last resort" medicine
      to treat bacterial infections. Carbapenem-hydrolyzing beta-lactamases (also
      called carbapenemases), however, can confer bacterial resistance and represent a
      serious health threat. Here, we report a novel approach using (18)O labeling and
      selected reaction monitoring to detect carbapenemase activity from pathogenic
      microorganisms in a rapid and quantitative manner. Four model bacterial strains
      bearing various classes of beta-lactamases were tested for their capability to
      hydrolyze Meropenem, an FDA-approved carbapenem drug. We were able to predict the
      Meropenem resistance of these bacteria on the basis of their carbapenemase
      activity, suggesting the great potential of our method in clinical diagnostics. 

PMID- 24131332
TI  - Ordered structure rearrangements in heated gold nanocrystal superlattices.
AB  - Small-angle X-ray scattering (SAXS) data reveal that superlattices of organic
      ligand-stabilized gold (Au) nanocrystals can undergo a series of ordered
      structure transitions at elevated temperature. An example is presented of a body
      centered cubic superlattice that evolves into a hexagonal close-packed structure,
      followed by the formation of binary simple cubic AB13 and hexagonal AB5
      superlattices. Ultimately the superlattice decomposes at high temperature to
      bicontinuous domains of coalesced Au and intervening hydrocarbon. Transmission
      electron microscopy revealed that the ordered structure transformations result
      from partial ligand desorption and controlled Au nanocrystal growth during
      heating, which forces changes in superlattice symmetry. These observations
      suggest some similarity between organic ligand-coated nanocrystals and microphase
      segregated diblock copolymers, where thermally induced nanophase-segregation of
      Au and organic ligand influences the ordered arrangements in the superlattice. 

PMID- 24131333
TI  - Cell death induced by AC magnetic fields and magnetic nanoparticles: current
      state and perspectives.
AB  - This review analyses the advances in the field of magnetically induced cell death
      using intracellular magnetic nanoparticles (MNPs). Emphasis has been given to in
      vitro research results, discussing the action of radiofrequency (RF) waves on
      biological systems as well as those results of thermally induced cell death in
      terms of MNP cell interactions. Our main goal has been to provide a unified
      depiction of many recent experiments and theoretical models relevant to the
      effect of applied electromagnetic fields on MNPs after cellular uptake and the
      cytotoxicity assessment of MNPs. We have addressed the effects of RF waves used
      for in vitro magnetic hyperthermia on eukaryotic cells regarding physical
      modifications of the cellular local environment and cell viability.

PMID- 24131335
TI  - DNA damage by the direct effect of ionizing radiation: products produced by two
      sequential one-electron oxidations.
AB  - It has long been assumed that the population of radicals trapped in irradiated
      DNA (that is, the radicals escaping recombination) would quantitatively account
      for the lesions observed in DNA. Recent results indicate that this is not the
      case. The yield of DNA lesions exceed the yield of trappable radicals. To account
      for a portion of this shortfall, it is thought that some of the initially formed
      2'-deoxyribose radicals undergo a second oxidation by nearby base cation radicals
      to form 2'-carbocations. The carbocations react to give strand breaks and free
      base release. Schemes are presented to account for the major oxidation products
      observed including 8-oxoGua, 8-oxoAde, 5-OHMeUra, and free base release.
      Theoretical calculations were performed to ascertain the likelihood of the second
      oxidation step in these reaction pathways actually occurring, and to account for
      base sequence dependence and various levels of hydration. 

PMID- 24131334
TI  - The roles of the central executive and visuospatial storage in mental arithmetic:
      a comparison across strategies.
AB  - Previous research has demonstrated that working memory plays an important role in
      arithmetic. Different arithmetical strategies rely on working memory to different
      extents-for example, verbal working memory has been found to be more important
      for procedural strategies, such as counting and decomposition, than for retrieval
      strategies. Surprisingly, given the close connection between spatial and
      mathematical skills, the role of visuospatial working memory has received less
      attention and is poorly understood. This study used a dual-task methodology to
      investigate the impact of a dynamic spatial n-back task (Experiment 1) and tasks
      loading the visuospatial sketchpad and central executive (Experiment 2) on
      adults' use of counting, decomposition, and direct retrieval strategies for
      addition. While Experiment 1 suggested that visuospatial working memory plays an
      important role in arithmetic, especially when counting, the results of Experiment
      2 suggested this was primarily due to the domain-general executive demands of the
      n-back task. Taken together, these results suggest that maintaining visuospatial
      information in mind is required when adults solve addition arithmetic problems by
      any strategy but the role of domain-general executive resources is much greater
      than that of the visuospatial sketchpad. 

PMID- 24131337
TI  - Traumatic brain injury in veterans of the wars in Iraq and Afghanistan:
      communication disorders stratified by severity of brain injury.
AB  - OBJECTIVE: To describe the prevalence of communication disorders in veterans of
      the wars in Iraq and Afghanistan with traumatic brain injury (TBI). DESIGN:
      Retrospective study of the prevalence of aphasia, fluency and voice disorders
      among veterans with different severity levels of TBI. Data was obtained from the
      VA National repository for OEF/OIF/OND veterans who received VA care in Fiscal
      Years 2010 and 2011. RESULTS: Among the 303,716 veterans in this study, 1848 were
      diagnosed with a communication disorder; 40% of these were also diagnosed with a
      TBI. Voice disorders were the most prevalent diagnosis (3.5 per 1000) followed by
      aphasia (1.9 per 1000) and fluency disorder (0.7 per 1000). Individuals with a
      TBI diagnosis were more likely to have a diagnosis of aphasia, followed by
      fluency and then voice disorder. The odds ratio (OR) of aphasia with TBI was
      11.09-252.75 (95% CI = 8.78-441.52, p < 0.01). OR for fluency disorders with TBI
      was 3.58-10.41 (95% CI = 2.56-42.40, p < 0.01) and association of voice disorders
      with TBI was significant for all levels of TBI severity (OR = 1.5-6.61, 95% CI =
      1.24-14.05, p < 0.01). CONCLUSIONS: Veterans who sustained a TBI were more likely
      to have a diagnosis of a communication disorder, regardless of TBI severity.
      Those with TBI, including mild TBI, should be screened and evaluated for
      communication disorders.

PMID- 24131336
TI  - Vitiligo and alopecia areata: apples and oranges?
AB  - Vitiligo and alopecia areata are common autoimmune diseases of the skin. Vitiligo
      is caused by the destruction of melanocytes and results in the appearance of
      white patches on any part of the body, while alopecia areata is characterized by
      patchy hair loss primarily on the scalp, but may also involve other areas as
      well. At first glance, the two diseases appear to be quite different, targeting
      different cell types and managed using different treatment approaches. However,
      the immune cell populations and cytokines that drive each disease are similar,
      they are closely associated within patients and their family members, and
      vitiligo and alopecia areata have common genetic risk factors, suggesting that
      they share a similar pathogenesis. Like apples and oranges, vitiligo and alopecia
      areata have some obvious differences, but similarities abound. Recognizing both
      similarities and differences will promote research into the pathogenesis of each
      disease, as well as the development of new treatments. 

PMID- 24131338
TI  - Predictors of relapse in patients with ulcerative colitis in remission after one
      year of infliximab therapy.
AB  - BACKGROUND. Some of the most important questions relating to the use of
      biological therapy in inflammatory bowel diseases concern the duration of
      maintenance therapy. The RASH study revealed that previous use of biological
      therapy and dose intensification are associated with restarting of biological
      therapy in Crohn's disease. The aim of the study was to assess the disease course
      and frequency of relapse of ulcerative colitis (UC) following discontinuation of
      infliximab in patients with remission and to determine predictive factors for
      relapse. PATIENTS AND METHODS. Fifty-one UC patients who had achieved clinical
      remission following 1 year of infliximab therapy and for whom infliximab was then
      discontinued participated in this prospective observational study. 15.7% of the
      patients received infliximab before the 1-year period of biological therapy
      analyzed in the study. Biological therapy was restarted in case of recurrent
      clinical activity. Data were collected from four Hungarian IBD centers. RESULTS.
      Thirty-five percent of the patients needed to be retreated with infliximab within
      1 year after treatment cessation. Logistic regression analysis revealed that
      previous biological therapy (p = 0.021) was associated with the need of
      restarting infliximab. None of the data relating to patients' demographic and
      clinical characteristics, concomitant therapy and CRP level showed association
      with the need for restarting biological therapy. CONCLUSIONS. Biological therapy
      was restarted at a median of 4 months after discontinuation in more than every
      third UC patients who had been in clinical remission following 1 year of
      infliximab therapy. Response to retreatment with infliximab was favorable in the
      majority of the patients who relapsed.

PMID- 24131339
TI  - Measuring angiotensin-I converting enzyme inhibitory activity by micro plate
      assays: comparison using marine cryptides and tentative threshold determinations
      with captopril and losartan.
AB  - To determine the angiotensin-I converting enzyme (ACE) inhibitory activity of
      marine cryptides, different methods were tested. ACE inhibition was measured
      using two synthetic substrates, (N-[3-(2-furyl) acryloyl]-Phe-Gly-Gly (FAPGG) and
      N-hippuryl-His-Leu hydrate salt (HHL)), and a natural one, angiotensin-I. The
      IC50 value (defined as the concentration of inhibitory molecule needed to inhibit
      50% of the ACE activity) of the reference synthetic inhibitor captopril was in
      the nanomolar range (1.79-15.1 nM) when synthetic substrates were used, whereas
      it exhibited IC50 of micromolar range (16.71 MUM) with angiotensin-I. We chose
      losartan, an antagonist of angiotensin-II receptor as negative control for the
      ACE inhibition. Losartan was also able to inhibit ACE whatever the substrate
      tested, with IC50 of micromolar range (17.13-146 MUM). We defined this value as a
      limit above which molecules are not showing in vitro ACE inhibitory activity. Val
      Trp (VW), Val-Tyr (VY), Lys-Tyr (KY), Lys-Trp (KW), Ile-Tyr (IY), Ala-Pro (AP),
      Val-Ile-Tyr (VIY), Leu-Lys-Pro (LKP), Gly-Pro-Leu (GPL), Ala-Lys-Lys (AKK), and
      Val-Ala-Pro (VAP) were tested as inhibitors of ACE with synthetic and natural
      substrates. IC50 displayed were substrate-dependent. With FAPGG as substrate, IW,
      VAP, KY, IY, AP, AKK, and VIY show IC50 values over the IC50 value of losartan
      and should not be considered as inhibitors of ACE. VY, VW, KW, and LKP exhibited
      IC50 value lower than the IC50 value of losartan for all substrates tested and
      were thus considered as good candidates for effectively decreasing hypertension.
      It appears that the comparison of IC50 is not consistent when IC50 values are
      obtained with different substrates and different methods. In vitro ACE inhibitory
      activity assays should always include various ACE substrates and references such
      as captopril and a negative control to obtain data reliable to discriminate ACE
      inhibitory peptides. 

PMID- 24131340
TI  - Phlyctenular keratoconjunctivitis associated with Dolosigranulum pigrum.

PMID- 24131341
TI  - Danish surgeons' views on minimally invasive surgery.
AB  - BACKGROUND AND AIM: Advancements in minimally invasive surgery have led to
      increases in popularity of single-incision laparoscopic surgery (SILS) and
      natural orifice translumenal surgery (NOTES((r)); American Society for
      Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American
      Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) due to their
      postulated benefits of better cosmesis, less pain, and quicker recovery. This
      questionnaire-based study investigated Danish surgeons' attitudes toward these
      new procedures. SUBJECTS AND METHODS: A 26-item questionnaire was developed and
      distributed electronically via e-mail to a total of 1253 members of The Danish
      Society of Surgeons and The Danish Society of Young Surgeons. RESULTS: In total,
      352 (approximately 30%) surgeons completed the questionnaire, 54.4% were over 50
      years of age, and 76.6% were men. When choosing surgery, the most important
      factors taken into consideration were the risk of complication and short
      convalescence, whereas the least important factors were cosmesis and option of
      local anaesthesia. If the surgeons themselves were to undergo cholecystectomy,
      35.5% would choose SILS, and 14.5% would choose NOTES provided that the risk was
      equal to traditional laparoscopy (3%). The fraction of surgeons willing to learn
      SILS and NOTES was 44.6% and 32.7%, respectively. The desire to learn was higher
      among less experienced and surgically active surgeons. Of the responders, 68.8%
      considered SILS and 43.2% considered NOTES would become standard techniques for
      cholecystectomy within 6 years. CONCLUSIONS: The importance of risk of
      complications has not surprisingly a high priority among surgeons in this
      questionnaire. Why this is has to be investigated further before implementing
      SILS and NOTES as standard of care.

PMID- 24131342
TI  - Mesh/Meshless paraumbilical hernia repair with concomitant single-incision
      transumbilical three-port laparoscopic cholecystectomy-prospective observational
      study of 126 patients.
AB  - BACKGROUND: Paraumbilical hernia with benign gallbladder disease forms a
      challenging combination for offering benefits of single-incision surgery. The
      purpose of this prospective observational study was to assess the outcomes of
      paraumbilical hernia repair performed concomitantly with three-port laparoscopic
      cholecystectomy through the same periumbilical incision using routine
      instruments. PATIENTS AND METHODS: In total, 126 subjects formed the patient
      cohort. The mean age for females was 38.5 years, and that for the males was 40
      years. The periumbilical curved incision accommodated three independent ports for
      conducting the cholecystectomy. The subsequent choice for the hernia repair was
      subject to the size (diameter) of the defect. Defects <4 cm in diameter (n=96)
      were suture-closed without mesh reinforcement. For defects 5-8-cm in diameter
      (n=33), an innovative technique of inserting all three ports directly into the
      peritoneal/hernial sac in a triangular manner was used for the cholecystectomy.
      Such a hernia defect was then reinforced with preperitoneal polypropylene mesh
      before closing it primarily after releasing the posterior rectus sheath. However,
      defects >8 cm were excluded from the study. RESULTS: The mean operative time was
      75 minutes. Patients were discharged after a mean of 1.5 days. Four patients were
      converted to conventional laparoscopic cholecystectomy owing to technical
      difficulty. An umbilical seroma occurred in 3 patients. Over the mean follow-up
      of 38.5 months, none of the patients had paraumbilical hernia recurrence. A
      hernial sac was used to space out the ports. The morbidity of the procedure was
      acceptable. CONCLUSIONS: Concomitant paraumbilical repair and cholecystectomy by
      the technique described is effective and safe for select patients. Prosthetic
      reinforcement is advisable for hernia defects with a diameter of 5-8 cm.

PMID- 24131343
TI  - Identifying individual common carp Cyprinus carpio using scale pattern.
AB  - Volunteers were able to match photographs of the same common carp Cyprinus carpio
      taken on two occasions. Images were identified correctly on 95.76% of occasions.
      Thus, scale patterns can be used for non-invasive identification of C. carpio
      over a period of time. 

PMID- 24131344
TI  - Stress, interviewer support, and children's eyewitness identification accuracy.
AB  - Few studies have investigated how stress affects eyewitness identification
      capabilities across development, and no studies have investigated whether
      retrieval context in conjunction with stress affects accuracy. In this study, one
      hundred fifty-nine 7- to 8- and 12- to 14-year-olds completed a high- or low
      stress laboratory protocol during which they interacted with a confederate. Two
      weeks later, they attempted to identify the confederate in a photographic lineup.
      The lineup administrator behaved in either a supportive or a nonsupportive
      manner. Participants who experienced the high-stress event and were questioned by
      a supportive interviewer were most accurate in rejecting target-absent lineups.
      Results have implications for debates about effects of stress on eyewitness
      recall, how best to elicit accurate identifications in children, and
      developmental changes in episodic mnemonic processes. 

PMID- 24131345
TI  - Retropath: automated pipeline for embedded metabolic circuits.
AB  - Metabolic circuits are a promising alternative to other conventional genetic
      circuits as modular parts implementing functionalities required for synthetic
      biology applications. To date, metabolic design has been mainly focused on
      production circuits. Emergent applications such as smart therapeutics, however,
      require circuits that enable sensing and regulation. Here, we present RetroPath,
      an automated pipeline for embedded metabolic circuits that explores the circuit
      design space from a given set of specifications and selects the best circuits to
      implement based on desired constraints. Synthetic biology circuits embedded in a
      chassis organism that are capable of controlling the production, processing,
      sensing, and the release of specific molecules were enumerated in the metabolic
      space through a standard procedure. In that way, design and implementation of
      applications such as therapeutic circuits that autonomously diagnose and treat
      disease, are enabled, and their optimization is streamlined. 

PMID- 24131347
TI  - Enhancement of root hydraulic conductivity by methyl jasmonate and the role of
      calcium and abscisic acid in this process.
AB  - The role of jasmonic acid in the induction of stomatal closure is well known.
      However, its role in regulating root hydraulic conductivity (L) has not yet been
      explored. The objectives of the present research were to evaluate how JA
      regulates L and how calcium and abscisic acid (ABA) could be involved in such
      regulation. We found that exogenous methyl jasmonate (MeJA) increased L of
      Phaseolus vulgaris, Solanum lycopersicum and Arabidopsis thaliana roots. Tomato
      plants defective in JA biosynthesis had lower values of L than wild-type plants,
      and that L was restored by addition of MeJA. The increase of L by MeJA was
      accompanied by an increase of the phosphorylation state of the aquaporin PIP2. We
      observed that MeJA addition increased the concentration of cytosolic calcium and
      that calcium channel blockers inhibited the rise of L caused by MeJA. Treatment
      with fluoridone, an inhibitor of ABA biosynthesis, partially inhibited the
      increase of L caused by MeJA, and tomato plants defective in ABA biosynthesis
      increased their L after application of MeJA. It is concluded that JA enhances L
      and that this enhancement is linked to calcium and ABA dependent and independent
      signalling pathways.

PMID- 24131349
TI  - Hexameric resorcinarene capsule is a Bronsted acid: investigation and application
      to synthesis and catalysis.
AB  - Molecular capsules have attracted interest as simple enzyme mimetics and several
      examples of catalytic transformations in water-soluble metal-ligand based systems
      have been reported. This is not the case for hydrogen-bond based molecular
      capsules, which in contrast can be employed in organic solvents. We describe
      herein our investigations of such a system: The resorcin[4]arene hexamer is one
      of the largest hydrogen bond-based self-assembled capsules and has been studied
      intensively due to its ready availability. We present evidence that the capsule
      acts as a reasonably strong Bronsted acid (pKa approximately 5.5-6). This finding
      explains the capsule's high affinity toward tertiary amines that are protonated
      and therefore encounter cation-pi interactions inside the cavity. We were able to
      translate this finding into a first synthetic application: A highly substrate
      selective Wittig reaction. We also report that this property renders the capsule
      an efficient enzyme-like catalyst for substrate selective diethyl acetal
      hydrolysis. 

PMID- 24131350
TI  - Epidermal growth factor and epidermal growth factor signaling attenuate laser
      induced melanogenesis.
AB  - BACKGROUND: Epidermal growth factor (EGF) is a peptide that promotes cell growth
      by binding to its receptor (EGFR) on the cell surface. EGF has been used in
      cosmetics to whiten the skin and for the prevention of postinflammatory
      hyperpigmentation (PIH), presumably by accelerating wound healing, but the
      effects of EGF on melanogenesis are not known, and the presence of EGFR on
      melanocytes has not been confirmed. METHODS: To establish a role of EGF in
      melanogenesis, we first investigated expression of EGFR on melanocytes. Second,
      in the search for an effect of EGF on PIH, we investigated the effect of EGF on
      melanin production by melanocytes with or without laser-treated keratinocyte
      conditioned culture media (LCM). RESULTS: Treatment with EGF did not affect
      proliferation of melan-A, mouse-derived immortalized melanocytes. Melanocytes
      treated with LCM had greater prostaglandin-E2 (PGE2) expression and tyrosinase
      enzyme activity than melanocytes treated with control media. Treatment with EGF
      lowered melanin production of LCM-treated melanocytes but not of melanocytes
      treated with control media. CONCLUSION: Our results support EGF as a candidate
      target for development of antimelanogenic agents in PIH.

PMID- 24131353
TI  - Exploring conflict- and target-related movement of visual attention.
AB  - Intermixing trials of a visual search task with trials of a modified flanker
      task, the authors investigated whether the presentation of conflicting
      distractors at only one side (left or right) of a target stimulus triggers shifts
      of visual attention towards the contralateral side. Search time patterns provided
      evidence for lateral attention shifts only when participants performed the
      flanker task under an instruction assumed to widen the focus of attention,
      demonstrating that instruction-based control settings of an otherwise identical
      task can impact performance in an unrelated task. Contrasting conditions with
      response-related and response-unrelated distractors showed that shifting
      attention does not depend on response conflict and may be explained as stimulus
      conflict-related withdrawal or target-related deployment of attention. 

PMID- 24131354
TI  - Practical method to limit tip-sample contact stress and prevent wear in amplitude
      modulation atomic force microscopy.
AB  - Amplitude modulation atomic force microscopy (AM-AFM) is one of the most popular
      AFM modes because of the reduced tip-sample interaction, compared to contact mode
      AFM, and the ability to acquire high-resolution images while interrogating the
      sample's material composition through phase imaging. Despite the reduced tip
      sample interaction, tip and sample wear can occur through gradual atomic scale
      processes that can significantly accumulate due to the high frequency of the tip
      sample interaction and through high intermittent contact stresses. Starting from
      existing analytical formulations, we introduce a method for selecting an
      appropriate probe and free oscillation amplitude that avoids exceeding a critical
      contact stress to minimize tip/sample damage. The approach is presented for the
      case of both a Hertzian- and a Derjaguin-Muller-Toporov-like tip-sample contact.
      Stress maps and related simplified formulas are provided that enable one to
      determine allowable free oscillation amplitudes to stay below a target contact
      stress for given cantilever and sample parameters (combined into a single
      "cantilever-sample constant" that we introduce). Experimental results show how
      sharp silicon tips, either uncoated or coated with diamond-like carbon and
      silicon nitride, interacting with a hard and wear-resistant sample
      (ultrananocrystalline diamond) can be preserved while attaining high-quality AM
      AFM images by using our proposed scheme. We also show that using our analysis to
      select parameters that exceed the target contact stress indeed leads to
      significant tip wear. This method provides AM-AFM users with a better
      understanding of contact stresses and enables selection of AM-AFM cantilevers and
      experimental parameters that preserve the tip for long periods of use and
      prevents the sample from damage. 

PMID- 24131352
TI  - Jakpot! New small molecules in autoimmune and inflammatory diseases.
AB  - Cytokines are key mediators of the development and homeostasis of haematopoietic
      cells, critical for host defense, but also for the development of autoimmune and
      inflammatory diseases such as psoriasis or rheumatoid arthritis (RA). Blocking
      cytokines activity by interfering with the ligand-receptor association has been
      successfully employed to treat several immune disorders. A subgroup of cytokines
      signals through receptors requiring the association with a family of cytoplasmic
      protein tyrosine kinases known as Janus kinases (Jaks). Jaks have recently gained
      significant attention as therapeutic targets in inflammation and autoimmunity,
      and several Jak inhibitory small molecules have been developed. The first two Jak
      inhibitors, tofacitinib and ruxolitinib, have been approved for the treatment of
      RA and primary myelofibrosis, respectively. Efficacy and safety data suggest that
      some of these oral Jak inhibitors as well as their topical formulations may soon
      enter the daily clinical practice for treating patients with psoriasis, lupus
      erythematosus or other inflammatory skin diseases. While biologics typically
      target one single cytokine, these new immunomodulators can inhibit signals from
      multiple cytokines intra-cellularly and therefore could be useful when other
      therapies are ineffective. Thus, Jak inhibitors may replace some traditional
      immunosuppressive agents and help patients not responding to previous therapies. 

PMID- 24131355
TI  - Development of thiolated poly(acrylic acid) microparticles for the nasal
      administration of exenatide.
AB  - The purpose of this study was to develop a microparticulate formulation for nasal
      delivery of exenatide utilizing a thiolated polymer. Poly(acrylic acid)-cysteine
      (PAA-cys) and unmodified PAA microparticles loaded with exenatide were prepared
      via coprecipitation of the drug and the polymer followed by micronization.
      Particle size, drug load and release of incorporated exenatide were evaluated.
      Permeation enhancing properties of the formulations were investigated on excised
      porcine respiratory mucosa. The viability of the mucosa was investigated by
      histological studies. Furthermore, ciliary beat frequency (CBF) studies were
      performed. Microparticles displayed a mean size of 70-80 um. Drug encapsulation
      was ~80% for both thiolated and non-thiolated microparticles. Exenatide was
      released from both thiolated and non-thiolated particles in comparison to
      exenatide in buffer only within 40 min. As compared to exenatide dissolved in
      buffer only, non-thiolated and thiolated microparticles resulted in a 2.6- and
      4.7-fold uptake, respectively. Histological studies performed before and after
      permeation studies showed that the mucosa is not damaged during permeation
      studies. CBF studies showed that the formulations were cilio-friendly. Based on
      these results, poly(acrylic acid)-cysteine-based microparticles seem to be a
      promising approach starting point for the nasal delivery of exenatide.

PMID- 24131356
TI  - Accurate spectroscopic models for methane polyads derived from a potential energy
      surface using high-order contact transformations.
AB  - A new spectroscopic model is developed for theoretical predictions of vibration
      rotation line positions and line intensities of the methane molecule. Resonance
      coupling parameters of the effective polyad Hamiltionians were obtained via high
      order contact transformations (CT) from ab initio potential energy surface. This
      allows converging vibrational and rotational levels to the accuracy of best
      variational calculations. Average discrepancy with centers of 100 reliably
      assigned experimental bands up to the triacontad range was 0.74 cm(-1) and 0.001
      cm(-1) for GS rotational levels up to J = 17 in direct CT calculations without
      adjustable parameters. A subsequent "fine tuning" of the diagonal parameters
      allows achieving experimental accuracy for about 5600 Dyad and Pentad line
      positions, whereas all resonance coupling parameters were held fixed to ab initio
      values. Dipole transition moment parameters were determined from selected ab
      initio line strengths previously computed from a dipole moment surface by
      variational method. New polyad model allows generating a spectral line list for
      the Dyad and Pentad bands with the accuracy ~10(-3) cm(-1) for line positions
      combined with ab initio predictions for line intensities. The overall integrated
      intensity agreement with Hitran-2008 empirical database is of 4.4% for the Dyad
      and of 1.8% for the Pentad range.

PMID- 24131357
TI  - Bilateral hypopyon uveitis secondary to mycosis fungoides with Sezary syndrome.

PMID- 24131358
TI  - The psychological effects of ostracism following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This study examines the psychological effects of ostracism. It
      was predicted that adults with brain injury would have an attenuated response to
      an acute experience of ostracism. RESEARCH DESIGN: A within-subject, fixed order
      design was used. The two conditions were ostracism and inclusion. METHODS AND
      PROCEDURES: A group of 20 adults with severe traumatic brain injury (TBI) were
      compared with a group of 19 matched control participants. Both groups
      participated in a pseudo online ball tossing game, Cyberball. On one occasion
      they were excluded from the game and on the following occasion they were included
      fairly. Following each game they completed a self-report questionnaire about
      their experience. MAIN OUTCOMES AND RESULTS: Persons with brain injury self
      reported negative psychological effects of ostracism including a lower sense of
      belonging, self-esteem and meaningful existence, however, were affected to a
      lesser degree than control participants [F(1,37) = 5.39, p = 0.026]. Persons with
      brain injury also reported that their feelings were hurt to a lesser extent than
      did control participants, t(37) = 2.10, p = 0.04. CONCLUSIONS: These results are
      discussed in terms of the role of the negative experience of ostracism in
      motivating and guiding behaviour to re-establish group membership to prevent
      future social isolation.

PMID- 24131359
TI  - Efficacy and safety of endoscopic submucosal dissection in treating gastric
      subepithelial tumors originating in the muscularis propria layer: a single-center
      study of 144 cases.
AB  - OBJECTIVE. Subepithelial tumors (SETs) in the stomach are usually considered
      benign. However, some do have potential for malignant transformation, especially
      when originating in the muscularis propria (MP). Our study aimed to evaluate the
      clinical efficacy and safety of endoscopic submucosal dissection (ESD) for
      gastric SETs originating in MP. MATERIAL AND METHODS. A total of 145 gastric MP
      SETs in 144 patients were treated by ESD between September 2008 and December
      2012. Characteristics of patients and SETs, therapeutic outcomes, pathologic
      characteristics, complications and follow-up outcomes were evaluated. RESULTS.
      Among the 144 patients, 104 were female (72.22%) and 40 were male (27.78%), and
      the mean age was 55.75 +/- 11.29 years (range 18-78 years). The mean size of the
      tumors determined by endoscopic ultrasound (EUS) was 15.14 +/- 9.70 mm (range 3
      50 mm). En bloc complete resection was achieved in 134 of 145 tumors, giving a
      complete resection rate of 92.41%. The final histopathologic diagnoses included
      52 leiomyomas, 89 gastrointestinal stromal tumors, 3 neurogenic tumors and 1
      lipoma. Perforations occurred in 21 patients (14.48%) and were endoscopically
      repaired with clips or nylon bands. Intraoperative bleeding occurred in seven
      patients (4.83%) and was corrected with argon plasma coagulation (APC) or hot
      biopsy forceps. No local recurrence or distant metastasis was detected during a
      mean follow-up of 19.14 +/- 10.29 months (range 3-51 months). CONCLUSIONS. ESD
      appears to be an effective and safe treatment for gastric SETs originating in MP.

PMID- 24131361
TI  - Opto-mechanical scission of polymer chains in photosensitive diblock-copolymer
      brushes.
AB  - In this paper we report on an opto-mechanical scission of polymer chains within
      photosensitive diblock-copolymer brushes grafted to flat solid substrates. We
      employ surface-initiated polymerization of methylmethacrylate (MMA) and t-butyl
      methacrylate (tBMA) to grow diblock-copolymer brushes of poly(methylmethacrylate
      b-t-butyl methacrylate) following the atom transfer polymerization (ATRP) scheme.
      After the synthesis, deprotection of the PtBMA block yields poly(methacrylic
      acid) (PMAA). To render PMMA-b-PMAA copolymers photosensitive, cationic
      azobenzene containing surfactants are attached to the negatively charged outer
      PMAA block. During irradiation with an ultraviolet (UV) interference pattern, the
      extent of photoisomerization of the azobenzene groups varies spatially and
      results in a topography change of the brush, i.e., formation of surface relief
      gratings (SRG). The SRG formation is accompanied by local rupturing of the
      polymer chains in areas from which the polymer material recedes. This opto
      mechanically induced scission of the polymer chains takes place at the interfaces
      of the two blocks and depends strongly on the UV irradiation intensity. Our
      results indicate that this process may be explained by employing classical
      continuum fracture mechanics, which might be important for tailoring the
      phenomenon for applying it to poststructuring of polymer brushes. 

PMID- 24131360
TI  - The secondary metabolism glycosyltransferases UGT73B3 and UGT73B5 are components
      of redox status in resistance of Arabidopsis to Pseudomonas syringae pv. tomato.
AB  - Secondary metabolism plant glycosyltransferases (UGTs) ensure conjugation of
      sugar moieties to secondary metabolites (SMs) and glycosylation contributes to
      the great diversity, reactivity and regulation of SMs. UGT73B3 and UGT73B5, two
      UGTs of Arabidopsis thaliana (Arabidopsis), are involved in the hypersensitive
      response (HR) to the avirulent bacteria Pseudomonas syringae pv. tomato (Pst
      AvrRpm1), but their function in planta is unknown. Here, we report that ugt73b3,
      ugt73b5 and ugt73b3 ugt73b5 T-DNA insertion mutants exhibited an accumulation of
      reactive oxygen species (ROS), an enhanced cell death during the HR to Pst
      AvrRpm1, whereas glutathione levels increased in the single mutants. In silico
      analyses indicate that UGT73B3 and UGT73B5 belong to the early salicylic acid
      (SA)-induced genes whose pathogen-induced expression is co-regulated with genes
      related to cellular redox homeostasis and general detoxification. Analyses of
      metabolic alterations in ugt mutants reveal modification of SA and scopoletin
      contents which correlate with redox perturbation, and indicate quantitative
      modifications in the pattern of tryptophan-derived SM accumulation after Pst
      AvrRpm1 inoculation. Our data suggest that UGT73B3 and UGT73B5 participate in
      regulation of redox status and general detoxification of ROS-reactive SMs during
      the HR to Pst-AvrRpm1, and that decreased resistance to Pst-AvrRpm1 in ugt
      mutants is tightly linked to redox perturbation. 

PMID- 24131362
TI  - Long-term-average spectrum characteristics of Kunqu Opera singers' speaking,
      singing and stage speech.
AB  - Long-term-average spectrum (LTAS) characteristics were analyzed for ten Kunqu
      Opera singers, two in each of five roles. Each singer performed singing, stage
      speech, and conversational speech. Differences between the roles and between
      their performances of these three conditions are examined. After compensating for
      Leq difference LTAS characteristics still differ between the roles but are
      similar for the three conditions, especially for Colorful face (CF) and Old man
      roles, and especially between reading and singing. The curves show no evidence of
      a singer's formant cluster peak, but the CF role demonstrates a speaker's formant
      peak near 3 kHz. The LTAS characteristics deviate markedly from non-singers'
      standard conversational speech as well as from those of Western opera singing.

PMID- 24131363
TI  - You better stop! Binding "stop" tags to irrelevant stimulus features.
AB  - We investigated whether the basic process of integrating stimuli (and their
      features) with simultaneously executed responses transfers to situations in which
      one does not respond to a stimulus. In three experiments, a stop-signal task was
      combined with a sequential priming paradigm to test whether irrelevant stimulus
      features become associated with a "stop" tag. Stopping a simple response during
      the prime trial delayed responding and facilitated stopping in the probe if the
      same irrelevant stimulus feature was repeated in the probe. These repetition
      priming effects were independent of the relation between the to-be-executed (or
      to-be-stopped) responses in the prime and probe, indicating that "stop" tags are
      global ("stop all responses!") rather than being response-related (e.g., "stop
      left response!").

PMID- 24131364
TI  - Importance of thiol-functionalized molecules for the structure and properties of
      compression-molded glassy wheat gluten bioplastics.
AB  - High-temperature compression molding of wheat gluten at low water levels yields a
      rigid plastic-like material. We performed a systematic study to determine the
      effect of additives with multiple thiol (SH) groups on gluten network formation
      during processing and investigate the impact of the resulting gluten network on
      the mechanical properties of the glassy end product. To this end, a fraction of
      the hydroxyl groups of different polyols was converted into SH functionalities by
      esterifying with 3-mercaptopropionic acid (MPA). The monofunctional additive MPA
      was evaluated as well. During low-temperature mixing SH-containing additives
      decreased the gluten molecular weight, whereas protein cross-linking occurred
      during high-temperature compression molding. The extent of both processes
      depended on the molecular architecture of the additives and their concentration.
      After molding, the material strength and failure strain increased without
      affecting the modulus, provided the additive concentration was low. The strength
      decreased again at too high concentrations for polyols with low SH
      functionalization. Attributing these effects solely to the interplay of
      plasticization and the SH-facilitated introduction of cross-links is inadequate,
      since an improvement in both strength and failure strain was also observed in the
      presence of high levels of MPA. It is hypothesized that, regardless of the
      molecular structure of the additive, the presence of SH-containing groups induces
      conformational changes which contribute to the mechanical properties of glassy
      gluten materials. 

PMID- 24131365
TI  - Membranes with highly ordered straight nanopores by selective swelling of fast
      perpendicularly aligned block copolymers.
AB  - Membranes with uniform, straight nanopores have important applications in diverse
      fields, but their application is limited by the lack of efficient producing
      methods with high controllability. In this work, we reported on an extremely
      simple and efficient strategy to produce such well-defined membranes. We
      demonstrated that neutral solvents were capable of annealing amphiphilic block
      copolymer (BCP) films of polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) with
      thicknesses up to 600 nm to the perpendicular orientation within 1 min. Annealing
      in neutral solvents was also effective to the perpendicular alignment of block
      copolymers with very high molecular weights, e.g., 362 000 Da. Remarkably, simply
      by immersing the annealed BCP films in hot ethanol followed by drying in air, the
      originally dense BCP films were nondestructively converted into porous membranes
      containing highly ordered, straight nanopores traversing the entire thickness of
      the membrane (up to 1.1 MUm). Grazing incident small-angle X-ray spectroscopy
      confirmed the hexagonal ordering of the nanopores over large areas. We found that
      the overflow of P2VP chains from their reservoir P2VP cylinders and the
      deformation of the PS matrix in the swelling process contributed to the
      transformation of the solid P2VP cylinders to empty straight pores. The pore
      diameters can be tuned by either changing the swelling temperatures or depositing
      thin layers of metal oxides on the preformed membranes via atomic layer
      deposition with a subnanometer accuracy. To demonstrate the application of the
      obtained porous membranes, we used them as templates and produced centimeter
      scale arrays of aligned nanotubes of metal oxides with finely tunable wall
      thicknesses. 

PMID- 24131366
TI  - Correction to "Real-Time Observation of Multiple-Protein Complex Formation with
      Single-Molecule FRET".

PMID- 24131367
TI  - The protein kinase C inhibitor sotrastaurin allows regulatory T cell function.
AB  - The novel immunosuppressant sotrastaurin is a selective inhibitor of protein
      kinase C isoforms that are critical in signalling pathways downstream of the T
      cell receptor. Sotrastaurin inhibits nuclear factor (NF)-kappaB, which directly
      promotes the transcription of forkhead box protein 3 (FoxP3), the key regulator
      for the development and function of regulatory T cells (Tregs). Our center
      participated in a randomized trial comparing sotrastaurin (n = 14) and the
      calcineurin inhibitor Neoral (n = 7) in renal transplant recipients. We conducted
      ex vivo mixed lymphocyte reaction (MLR) and flow cytometry studies on these
      patient samples, as well as in vitro studies on samples of blood bank volunteers
      (n = 38). Treg numbers remained stable after transplantation and correlated with
      higher trough levels of sotrastaurin (r = 0.68, P = 0.03). A dose-dependent
      effect of sotrastaurin on alloresponsiveness was observed: the half maximal
      inhibitory concentration (IC50 ) to inhibit alloactivated T cell proliferation
      was 45 ng/ml (90 nM). In contrast, Treg function was not affected by
      sotrastaurin: in the presence of in vitro-added sotrastaurin (50 ng/ml) Tregs
      suppressed the proliferation of alloactivated T effector cells at a 1:5 ratio by
      35 versus 47% in the absence of the drug (P = 0.33). Signal transducer and
      activator of transcription 5 (STAT)-5 phosphorylation in Tregs remained intact
      after incubation with sotrastaurin. This potent Treg function was also found in
      cells of patients treated with sotrastaurin: Tregs inhibited the anti-donor
      response in MLR by 67% at month 6, which was comparable to pretransplantation
      (82%). Sotrastaurin is a potent inhibitor of alloreactivity in vitro, while it
      did not affect Treg function in patients after kidney transplantation. 

PMID- 24131368
TI  - Is Grover's disease an autoimmune dermatosis?
AB  - Grover's disease (GD) is a transient or persistent, monomorphous,
      papulovesicular, asymptomatic or pruritic eruption classified as non-familial
      acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis
      remains controversial. The purpose of this study was to investigate antibody
      mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA
      and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used
      the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG
      autoantibody reactivities. Multiplex analysis of autoantibody responses revealed
      autoreactivity of all 11 GD patients with cellular proteins involved in the
      signal transduction events regulating cell development, activation, growth,
      death, adhesion and motility. Semiquantitative fluorescence analysis of cultured
      keratinocytes pretreated with sera from each patient demonstrated decreased
      intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera
      induced BAD expression, indicating that binding of autoantibodies to
      keratinocytes alters expression/function of their adhesion molecules and
      activates apoptosis. We also tested the ability of GD sera to induce visible
      alterations of keratinocyte shape and motility in vitro but found no specific
      changes. Thus, our results demonstrated that humoral autoimmunity in GD can be
      mediated by both IgA and IgG autoantibodies. At this point, however, it is
      impossible to conclude whether these autoantibodies cause or are caused by the
      disease. Antidesmoglein antibodies may be triggered by exposure to immune system
      of sequestered antigens due to disintegration of desmosomes during primary
      acantholysis. Clarifying aetiology of GD will help improve treatment, which
      currently is symptomatic and of marginal effectiveness. 

PMID- 24131369
TI  - The provision of feedback through computer-based technology to promote self
      managed post-stroke rehabilitation in the home.
AB  - PURPOSE: Building on previous research findings, this article describes the
      development of the feedback interfaces for a Personalised Self-Managed
      Rehabilitation System (PSMrS) for home-based post-stroke rehabilitation using
      computer-based technology. METHOD: Embedded within a realistic evaluative
      methodological approach, the development of the feedback interfaces for the PSMrS
      involved the incorporation of existing and emerging theories and a hybrid of
      health and social sciences research and user-centred design methods. RESULTS:
      User testing confirmed that extrinsic feedback for home-based post-stroke
      rehabilitation through computer-based technology needs to be personalisable,
      accurate, rewarding and measurable. In addition, user testing also confirmed the
      feasibility of using specific components of the PSMrS. CONCLUSIONS: A number of
      key elements are crucial for the development and potential utilisation of
      technology in what is an inevitable shift towards the use of innovative methods
      of delivering post-stroke rehabilitation. This includes the specific elements
      that are essential for the promotion of self-managed rehabilitation and
      rehabilitative behaviour change; the impact of the context on the mechanisms;
      and, importantly, the need for reliability and accuracy of the technology.

PMID- 24131370
TI  - Comparison of activities of daily living (ADLs) in two different one arm drive
      wheelchairs: a study of individuals/participants with hemiplegia.
AB  - AIMS: This pilot study measured activities of daily living performance in
      individuals/participants with hemiplegia propelling both a standard dual handrim
      Action 3 wheelchair and a standard Action 3 wheelchair with a Neater Uni
      Wheelchair kit attachment. The kit consists of a steerable front. RESEARCH
      QUESTIONS: Does the use of the NUW affect the performance quality of activities
      of daily living in individuals/participants with hemiplegia. Is there a
      difference in the motor and process skills during activities of daily living
      performance, and in the time taken to complete the activities. METHODS: Four
      individuals/participants with hemiplegia were used in a cross over, repeated
      measures trial. Assessment of Motor and Process Skills of users undertaking
      making a bed and laying a table "Swedish style", tasks were measured and time
      taken to complete each task were recorded. RESULTS: Bed making completion time
      was quicker in the Neater Uni-wheelchair (p < 0.03). Motor skills were
      significantly higher than the process ability skills (p < 0.05). CONCLUSION:
      Activities of daily living tasks in the Neater Uni-wheelchair were completed more
      efficiently with no loss in quality of motor and process skills performance. This
      suggests that the Neater Uni-wheelchair is a viable alternative to current one
      arm drive provision. Implications for Rehabilitation Inappropriate wheelchair
      provision can result in capacity limitation and poorer quality of ADL motor skill
      as well-lowered process performance skill. AMPS can help to explain motor and
      process skill differences in complex activities.

PMID- 24131371
TI  - Developing a personalised self-management system for post stroke rehabilitation;
      utilising a user-centred design methodology.
AB  - PURPOSE: To develop and evaluate an information and communication technology
      (ICT) solution for a post-stroke Personalised Self-Managed Rehabilitation System
      (PSMrS). The PSMrS translates current models of stroke rehabilitation and
      theories underpinning self-management and self-efficacy into an ICT-based system
      for home-based post-stroke rehabilitation. METHODS: The interdisciplinary
      research team applied a hybrid of health and social sciences research methods and
      user-centred design methods. This included a series of home visits, focus groups,
      in-depth interviews, cultural probes and technology biographies. RESULTS: The
      iterative development of both the content of the PSMrS and the interactive
      interfaces between the system and the user incorporates current models of post
      stroke rehabilitation and addresses the factors that promote self-managed
      behaviour and self-efficacy such as mastery, verbal persuasion and physiological
      feedback. CONCLUSION: The methodological approach has ensured that the
      interactive technology has been driven by the needs of the stroke survivors and
      their carers in the context of their journey to both recovery and adaptation.
      Underpinned by theories of motor relearning, neuroplasticity, self-management and
      behaviour change, the PSMrS developed in this study has resulted in a
      personalised system for self-managed rehabilitation, which has the potential to
      change motor behaviour and promote the achievement of life goals for stroke
      survivors.

PMID- 24131372
TI  - Use of non-insulin therapies for type 1 diabetes.

PMID- 24131373
TI  - Improved metabolic control in pediatric patients with type 1 diabetes: a
      nationwide prospective 12-year time trends analysis.
AB  - BACKGROUND: This study estimated temporal trends of metabolic control over 12
      years in a national cohort of childhood-onset type 1 diabetes. SUBJECTS AND
      METHODS: Data from the prospective childhood-onset diabetes register, which
      included 886 case subjects from 0 to 17.99 years of age at diagnosis and at least
      1 year of follow-up until the age of 22.99 years, were analyzed using
      multivariable linear and logistic regression models in the observational period
      between 2000 and 2011. RESULTS: Hemoglobin A1c (HbA1c) significantly decreased
      over 12 years, from 78 mmol/mol (interquartile range [IQR], 68-88 mmol/mol)
      (9.26% [IQR, 8.41-10.24%]) in the year 2000 to 61 mmol/mol (IQR, 55-67 mmol/mol)
      (7.75% [IQR, 7.20-8.30%]) in the year 2011 (P<0.001). HbA1c was significantly
      associated with age, treatment modality, and duration of diabetes (P<0.001), with
      females having on average 1.02% higher HbA1c (P=0.01; 95% confidence interval
      [CI] 1.005-1.035). The overall use of insulin pumps was 74%. The incidence rate
      of severe acute complications was low: 1.07 per 100 patient-years for severe
      diabetic ketoacidosis (95% CI 0.81-1.40) and 1.21 per 100 patient-years for
      severe (requiring intravenous or intramuscular therapy) hypoglycemia (95% CI 0.81
      1.40). CONCLUSIONS: The metabolic control of the entire nationwide pediatric type
      1 diabetes population significantly improved during the 12-year observational
      period with a low rate of severe acute complications events. The improvement was
      associated with the treatment modality. Additional efforts and solutions are
      necessary to further improve metabolic control and the quality of life of young
      people with type 1 diabetes.

PMID- 24131374
TI  - Carbapenem resistance and mortality in patients with Acinetobacter baumannii
      infection: systematic review and meta-analysis.
AB  - Acinetobacter baumannii has emerged as a major cause of healthcare-associated
      infections. Controversy exists as to whether antimicrobial resistance increases
      the risk of mortality. We conducted a systematic review and meta-analysis to
      examine this association. We searched MEDLINE and EMBASE databases up to May 2013
      to identify studies comparing mortality in patients with carbapenem-resistant A.
      baumannii (CRAB) vs. carbapenem-susceptible A. baumannii (CSAB). A random-effects
      model was used to pool Odds Ratios (OR). Heterogeneity was examined using I(2).
      We included 16 observational studies. There were 850 reported deaths (33%) among
      the 2546 patients. Patients with CRAB had a significantly higher risk of
      mortality than patients with CSAB in the pooled analysis of crude effect
      estimates (crude OR = 2.22; 95% CI = 1.66, 2.98), although substantial
      heterogeneity was evident (heterogeneity I(2) = 55%). The association remained
      significant in the pooled adjusted OR of 10 studies. Studies reported that
      patients with CRAB compared to patients with CSAB were more likely to have severe
      underlying illness and also to receive inappropriate empirical antimicrobial
      treatment, which increases the risk of mortality. Our study suggests that
      carbapenem resistance may increase the risk of mortality in patients with A.
      baumannii infection. However, cautious interpretation is required because of the
      residual confounding factors and inadequate sample size in most studies.

PMID- 24131375
TI  - Tethered aminohydroxylation: synthesis of the beta-amino acid of
      microsclerodermins A and B.
AB  - The utility of the tethered aminohydroxylation (TA) has been demonstrated by
      synthesis of the complex beta-amino acid residue of microsclerodermins A and B.
      The TA provided a regio- and stereoselective functionalization of a complex
      homoallylic alcohol. The route includes late-stage introduction of the aliphatic
      side chain via a cuprate addition and cross metathesis, a tactic designed to
      render the synthesis applicable to other microsclerodermins. 

PMID- 24131377
TI  - Theoretical study of topographical features around the conical intersections of 9
      (2-cyclopenten-1-ylidene)-9H-fluorene.
AB  - Ab initio molecular orbital calculations have been performed to examine the
      topographical features around the conical intersections (CIXs) for the
      photoisomerization of 9-(2-cyclopenten-1-ylidene)-9H-fluorene (CPF). The present
      study is motivated by the computational findings of the topographical features in
      the CIX region of a fluorene-based light-driven molecular motor with smooth
      rotation (denoted by M5-PCPF). CPF is a parent molecule of M5-PCPF but exhibits
      neither helicity nor unidirectionality. A stable geometry in S1 (S1-geometry) is
      located in the region where the ethylenic rotary axis is perpendicularly twisted,
      but the fluorene part wags little against the rotary axis, as is the case of M5
      PCPF. However, the topographical features around the CIXs of CPF are different
      from those of M5-PCPF. The wagging motion of the fluorene stator to the negative
      direction from S1-geometry leads straight to a CIX which implements forward and
      backward rotations. On the other hand, only the wagging motion to the positive
      direction does not lead to a CIX, and additional geometrical deformations are
      needed. Depending on the directions of additional geometrical deformations, two
      CIXs, which play the roles of respective exit channels for forward and backward
      rotations, are located in the positive wagging region. The difference in the
      topographical features in the CIX region between CPF and M5-PCPF is ascribed to
      the effect of the pentamethylene chain. By virtue of much less computational
      labor of CPF as well as the electronic structures being similar to those of M5
      PCPF, the intrinsic reaction coordinate was followed from the ethylenic pipi*
      state at the stable geometry in S0 into S1-geometry. Thereby, it was confirmed
      that a spectroscopically dark state due to the pi(fluorene)pi*(ethylene)
      excitation contributes less to the photochemical process of the ethylenic bond
      torsion, as is the case of M5-PCPF. 

PMID- 24131376
TI  - Site-specific stabilization of DNA by a tethered major groove amine, 7
      aminomethyl-7-deaza-2'-deoxyguanosine.
AB  - A cationic 7-aminomethyl-7-deaza-2'-deoxyguanosine (7amG) was incorporated site
      specifically into the self-complementary duplex d(G1A2G3A4X5C6G7C8T9C10T11C12)2
      (X = 7amG). This construct placed two positively charged amines adjacent to the
      major groove edges of two symmetry-related guanines, providing a model for
      probing how cation binding in the major groove modulates the structure and
      stability of DNA. Molecular dynamics calculations restrained by nuclear magnetic
      resonance (NMR) data revealed that the tethered cationic amines were in plane
      with the modified base pairs. The tethered amines did not form salt bridges to
      the phosphodiester backbone. There was also no indication of the amines being
      capable of hydrogen bonding to flanking DNA bases. NMR spectroscopy as a function
      of temperature revealed that the X5 imino resonance remained sharp at 55  degrees
      C. Additionally, two 5'-neighboring base pairs, A4:T9 and G3:C10, were stabilized
      with respect to the exchange of their imino protons with solvent. The equilibrium
      constant for base pair opening at the A4:T9 base pair determined by magnetization
      transfer from water in the absence and presence of added ammonia base catalyst
      decreased for the modified duplex compared to that of the A4:T9 base pair in the
      unmodified duplex, which confirmed that the overall fraction of the A4:T9 base
      pair in the open state of the modified duplex decreased. This was also observed
      for the G3:C10 base pair, where alphaK(op) for the G3:C10 base pair in the
      modified duplex was 3.0 * 106 versus 4.1 * 106 for the same base pair in the
      unmodified duplex. In contrast, equilibrium constants for base pair opening at
      the X5:C8 and C6:G7 base pairs did not change at 15  degrees C. These results
      argue against the notion that electrostatic interactions with DNA are entirely
      entropic and suggest that major groove cations can stabilize DNA via enthalpic
      contributions to the free energy of duplex formation.

PMID- 24131378
TI  - A novel cobalt-free, CO2-stable, and reduction-tolerant dual-phase oxygen
      permeable membrane.
AB  - A novel CO2-stable and reduction-tolerant Ce0.8Sm0.2O(2-delta)-La0.9Sr0.1FeO(3
      delta) (SDC-LSF) dense dual-phase oxygen-permeable membrane was designed and
      evaluated in this work. Homogeneous SDC-LSF composite powders for membrane
      fabrication were synthesized via a one-pot combustion method. The chemical
      compatibility and ion interdiffusion behavior between the fluorite phase SDC and
      perovskite phase LSF during the synthesis process was studied. The oxygen
      permeation flux through the dense dual-phase composite membranes was evaluated
      and found to be highly dependent on the volume ratio of SDC and LSF. The SDC-LSF
      membrane with a volume ratio of 7:3 (SDC70-LSF30) possessed the highest
      permeation flux, achieving 6.42 * 10(-7) mol.cm(-2).s(-1) under an air/CO
      gradient at 900  degrees C for a 1.1-mm-thick membrane. Especially, the membrane
      performance showed excellent durability and operated stably without any
      degradation at 900  degrees C for 450 h with helium, CO2, or CO as the sweep gas.
      The present results demonstrate that a SDC70-LSF30 dual-phase membrane is a
      promising chemically stable device for oxygen production and CO2 capture with
      sufficiently high oxygen permeation flux.

PMID- 24131379
TI  - Acute pancreatitis--costs for healthcare and loss of production.
AB  - OBJECTIVE. Severity of acute pancreatitis (AP) can vary from a mild to a
      fulminant disease with high morbidity and mortality. Cost analysis has, however,
      hitherto been sparse. The aim of this study was to calculate the cost of acute
      pancreatitis, both including hospital costs and costs due to loss of production.
      MATERIAL AND METHODS. All adult patients treated at Skane University Hospital,
      Lund, during 2009-2010, were included. A severity grading was conducted and cost
      analysis was performed on an individual basis. RESULTS. Two hundred and fifty-two
      patients with altogether 307 admissions were identified. Mean age was 60 +/- 19
      years, and 121 patients (48%) were men. Severe AP (SAP) was diagnosed in 38
      patients (12%). Thirteen patients (5%) died. Acute biliary pancreatitis was more
      costly than alcohol induced AP (p < 0.001). Total costs for treating mild AP
      (MAP) in patients <=65 years old was lower (p = 0.001) and costs for SAP was
      higher (p = 0.024), as compared to older patients. The overall hospital cost and
      cost for loss of production was per person in mean ?5,100 +/- 2,400 for MAP and
      ?28,200 +/- 38,100 for SAP (p < 0.001). The costs for treating AP during the two
      year-long study period were in mean ?9,762 +/- 19,778 per patient. Extrapolated
      to a national perspective, the annual financial burden for AP in Sweden would be
      ?38,500,000; corresponding to ?4,100,000 per million inhabitants. CONCLUSIONS.
      The costs of treating AP are high, especially in severe cases with a long ICU
      stay. These results highlight the need to optimize care and continue the
      identification and focus on SAP, in order to try to limit organ failure and
      infectious complications.

PMID- 24131380
TI  - Predictive value of selected biomarkers, polymorphisms, and clinical features for
      oligoarticular juvenile idiopathic arthritis-associated uveitis.
AB  - PURPOSE: Uveitis is the most common extra-articular manifestation of juvenile
      idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim
      of this study was to examine the risk factors associated with uveitis in
      oligoarticular JIA. METHODS: We conducted a chart review of 86 patients with
      oligoarticular JIA to assess if antinuclear antibody (ANA) status, gender, and
      age at JIA onset were associated with the development of uveitis. Biomarkers such
      as cytokine gene polymorphisms, erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) level were also assessed. RESULTS: Twenty-seven patients
      exhibited oligoarticular JIA-associated uveitis. Only the ESR at arthritis onset
      and the patient's age at arthritis onset were related to uveitis development in
      our patient sample. CONCLUSIONS: An age-associated risk of uveitis was observed
      in children younger than 3 years at the time of JIA onset. ESR values at
      arthritis onset higher than 22 mm/h were also related to uveitis development.

PMID- 24131381
TI  - In vitro evaluation of the efficacy of chicken egg yolk antibodies (IgY)
      generated against Propionibacterium acnes.
AB  - Acne vulgaris driven by multiple factors appears in almost two-third of the
      population. Increased resistance of the bacterium to antibiotics and cost
      effective treatments have made us resort to alternative therapy. OBJECTIVE: A
      novel method of targeting acne-causing bacterium Propionibacterium acnes with
      polyclonal chicken egg yolk antibodies was studied. METHODS: Anti
      Propionibacterium acnes antibodies were generated in white leghorn chickens by
      immunizing with antigen. The antibodies extracted from the egg yolk by
      polyethylene glycol method were subjected to the analysis. The antibody binding
      activity was evaluated by indirect ELISA. Further, inhibition efficiency of the
      antibodies was tested by growth inhibition assay, and biofilm inhibition was
      assessed by adherence test. RESULTS: Titration of antibodies determined by ELISA
      was found to 0.323 after the first booster dose. The qualitative test for the
      determination of the binding activity revealed significant reduction in the
      colonies. CONCLUSION: The results suggest that the egg yolk antibodies obtained
      from white leghorn chickens after immunization with the antigen may present as an
      alternative treatment option.

PMID- 24131382
TI  - Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting
      by topical delivery.
AB  - The clinical use of halobetasol propionate (HP) is related to some adverse
      effects like irritation, pruritus and stinging. The purpose of this work was to
      construct HP-loaded solid lipid nanoparticles (HP-SLN) formulation with skin
      targeting to minimizing the adverse side effects and providing a controlled
      release. HP-SLN were prepared by solvent injection method and formula was
      optimized by the application of 3(2) factorial design. The nanoparticulate
      dispersion was evaluated for particle size and entrapment efficiency (EE).
      Optimized batch was characterized for differential scanning calorimetry (DSC),
      scanning electron microscopy, X-ray diffraction study and finally incorporated
      into polymeric gels of carbopol for convenient application. The nanoparticulate
      gels were evaluated comparatively with the commercial product with respect to ex
      vivo skin permeation and deposition study on human cadaver skins and finally skin
      irritation study. HP-SLN showed average size between 200 nm and 84-94% EE. DSC
      studies revealed no drug-excipient incompatibility and amorphous dispersed of HP
      in SLN. Ex vivo study of HP-SLN loaded gel exhibited prolonged drug release up to
      12 h where as in vitro drug deposition and skin irritation studies showed that HP
      SLN formulation can avoid the systemic uptake, better accumulative uptake of the
      drug and nonirritant to the skin compared to marketed formulation. These results
      indicate that the studied HP-SLN formulation represent a promising carrier for
      topical delivery of HP, having controlled drug release, and potential of skin
      targeting with no skin irritation.

PMID- 24131383
TI  - Determination of the diffusion coefficient of protons in Nafion thin films by ac
      electrogravimetry.
AB  - This letter deals with an adaptation of the ac-electrogravimetry technique to
      extract separately the dynamic properties of H(+) and water in Nafion nanometric
      thin films (average thickness of 400 nm). An original theoretical approach was
      developed to extract the representative parameters from ac-electrogravimetry
      data. The concentration change of the exchanged species and the diffusion
      coefficient of the protons in a Nafion nanometric thin film (D = 0.5 * 10(-6)
      cm(2) s(-1) at 0.3 V vs SCE) were estimated for the first time according to the
      applied potential. The conductivity value of Nafion thin films was calculated
      from the Nernst-Einstein equation using diffusion coefficients and concentration
      values extracted from ac-electrogravimetry data. The calculated conductivity
      results agree well with the experimental proton conductivity values of Nafion
      thin films. 

PMID- 24131384
TI  - A non-coding mutation in the 5' untranslated region of patched homologue 1
      predisposes to basal cell carcinoma.
AB  - Mutations in the human homolog of the Drosophila patched gene, patched homologue
      1 (PTCH-1), are responsible for most hereditary and sporadic basal cell
      carcinomas. Here, we present a father and daughter with a high propensity for the
      development of basal cell carcinoma who were heterozygous for a non-coding
      germline mutation in the 5' untranslated region (UTR) of PTCH-1 (insertion of a
      surplus CGG triplet at the site of a seven times CGG repeat). We analysed the
      impact of this mutation on PTCH translation using a luciferase-based reporter
      vector. Insertion of an eighth CGG in the 5' UTR repressed protein translation
      dramatically when compared to the wild-type sequence. Our results suggest that
      this non-coding variant in the 5' UTR represents a mutation predisposing to basal
      cell carcinoma. 

PMID- 24131385
TI  - Consequences of surface neutralization in diblock copolymer thin films.
AB  - Two high-chi block copolymers, lamella-forming poly(styrene-block-[isoprene
      random-epoxyisoprene]) (PS-PEI78, with 78 mol % epoxidation) and lamella-forming
      poly(4-trimethylsilylstyrene-block-d,l-lactide) (PTMSS-PLA), were used to study
      three combinations of interfacial neutrality involving at least one neutral
      interface. PS-PEI78 annealed on a nonpreferential polymer mat (SMG) produced
      perpendicular lamellae independent of film thickness, indicating a neutral
      substrate and neutral free surface. In contrast, the presence of only one neutral
      interface results in the formation of surface topography ("islands" and "holes")
      with 0.5L0 step heights. PS-PEI78 (neutral free surface) annealed on PS brush (PS
      block preferential) forms "half" islands and holes. The inverse experiment, PTMSS
      PLA (with a PTMSS preferential free surface) annealed on a neutral (or near
      neutral) substrate surface, also generates 0.5L0 topography. These "half" island
      and hole structures are stable to extended thermal annealing. PS-PEI78 exposes
      both blocks at the free surface in contrast to PTMSS-PLA, which exposes just one.
      All three combinations of interfacial neutrality are explained by the precise
      balancing of the wetting tendencies of the two blocks. Evolution of the 0.5L0
      motifs appears to be facilitated by a preference to form half-period thick nuclei
      in the initial stages of morphological development. 

PMID- 24131386
TI  - Dissociating number line estimations from underlying numerical representations.
AB  - Estimation patterns in the number line task are usually interpreted to indicate
      the (logarithmic or linear) nature of the underlying mental number line. However,
      indicators of the to-be-achieved linear representation may also be confounded
      with task requirements or strategies to achieve optimal task performance. In this
      study, we dissociated correct task performance from indices of a linear
      representation. Therefore, we designed an experiment in which adults and first
      graders had to learn number-to-space mappings of nonlinear functions. For adults,
      we found better fits of the corresponding functions than a linear function after
      just a few minutes of training. For most first graders, estimation patterns were
      not fitted better by a logarithmic function when they had to learn a logarithmic
      layout. Thus, estimation patterns produced in the number line estimation task do
      not necessarily allow for valid inferences on the underlying representation of
      number magnitude. 

PMID- 24131387
TI  - Pulpal status of human primary molars with coexisting caries and physiological
      root resorption.
AB  - AIM: This study sought to investigate the effect of caries, in association with
      physiological root resorption, on the pulpal status of human primary molars.
      DESIGN: Fifty-three mandibular primary molars were obtained from children
      requiring extractions under general anaesthesia. Following extraction, teeth were
      split longitudinally and placed in Zamboni's fixative. Teeth were categorised
      according to i) the depth of caries (less than or greater than halfway through
      dentine thickness) and ii) the degree of physiological root resorption (<33%, 34
      66% or >67% of the root length). Ten-micrometre pulp sections were subject to
      indirect immunofluorescence using a combination of PGP 9.5 (a general neuronal
      marker), CD45 (a general neuronal marker), and Ulex europaeus agglutinin I (a
      marker of vascular endothelium). Image analysis was used to determine the
      percentage area of staining (PAS) for innervation and immune cells. RESULTS:
      Marked differences were seen between different samples, but there were no
      significant differences in mean PAS for PGP 9.5 or CD45 according to the degree
      of caries or extent of physiological root resorption (two-way anova, P > 0.05).
      CONCLUSION: Findings suggest that even if primary molars are undergoing
      exfoliation, they show comparable caries-induced changes to teeth without
      physiological root resorption, thus retaining potential for healing and repair.

PMID- 24131388
TI  - Antinuclear antibodies: two-step detection strategy.
AB  - In order to evaluate the performance of the chemiluminescent immunoassay (CLIA)
      in antinuclear antibodies (ANA) testing, using indirect fluorescent antibody
      (IFA) on HEp-2 cells as a standard, 209 samples were studied from September to
      October/2010. The tests were conducted according to the procedures recommended by
      the manufacturers of the reagents. The interpretation of the IFA results was done
      according to the Brazilian standards. The charts of patients showing different
      results between the two techniques were analyzed. The CLIA efficiency was 89%,
      with a sensitivity of 65%, and a specificity of 94.7%. Nine (4.3%) false-positive
      and 14 (6.7%) false-negative results were detected. Of these, 13 (93%)
      represented no risk for the diagnosis and therapeutic management of the patients.
      The CLIA methodology reduced the need for the IFA manual technique by 77%
      (160/209). The ANA screening test proved to be a fast and acceptable methodology
      in the studied population. We established the following criteria for the
      introduction of an automated ANA screening: (1) Positive results must be
      confirmed by IFA to characterize the pattern and titer of the antibody. (2)
      Negative results are issued with a notice to request a new test by IFA when the
      clinical suspicion of autoimmune disease persists. 

PMID- 24131389
TI  - Malignancies in patients with inflammatory bowel disease: a nationwide register
      study in Finland.
AB  - OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk
      of certain cancers. We assessed the long-term risks of malignancies among
      patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD
      (16,649 with UC and 5315 with CD) from the database of the Social Insurance
      Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up
      to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The
      numbers of cancers observed were compared to those expected in general population
      and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male
      patients with CD and UC had a slightly increased risk of malignancies. Patients
      with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence
      interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1),
      and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was
      highest among the youngest UC patients. Patients with CD had a significantly
      increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51,
      1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14
      5.85). In addition, the risk of basal cell skin cancer was increased in IBD
      (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and
      prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with
      CD and CU was higher than that in general population. Patients with UC are at
      increased risk for CRC and biliary tract cancers. CRC risk was highest in the
      youngest patients.

PMID- 24131390
TI  - Removal of naproxen and bezafibrate by activated sludge under aerobic conditions:
      kinetics and effect of substrates.
AB  - Naproxen and bezafibrate fall into the category of pharmaceuticals that have been
      widely detected in the aquatic environment, and one of the major sources is the
      effluent discharge from wastewater treatment plants. This study investigated the
      sorption and degradation kinetics of naproxen and bezafibrate in the presence of
      activated sludge under aerobic conditions. Experimental results indicated that
      the adsorption of pharmaceuticals by activated sludge was rapid, and the relative
      adsorbabilities of the two-target compounds were based on their log Kow and pKa
      values. The adsorption data could be well interpreted by the pseudo-second-order
      kinetic model. The degradation process could be described by the pseudo-first
      order kinetic model, whereas the pseudo-second-order kinetics were also well
      suited to describe the degradation process of the selected compounds at low
      concentrations. Bezafibrate was more easily degraded by activated sludge compared
      with naproxen. The spiked concentration of the two-target compounds was
      negatively correlated with k1 and k2s , indicating that the substrate inhibition
      effect occurred at the range of studied concentrations. Chemical oxygen demand
      (COD) did not associate with naproxen degradation; thus, COD is not an
      alternative method that could be applied to investigate natural organic matter's
      impact on degradation of pharmaceuticals by activated sludge. 

PMID- 24131391
TI  - Effects of pulsed electromagnetic field on intervertebral disc cell apoptosis in
      rats.
AB  - Despite numerous studies on pulsed electromagnetic field (PEMF) application, its
      effects of PEMF on intervertebral disc (IVD) have not yet been investigated in
      vivo. Accordingly, the effects of PEMF upon IVD in rats were evaluated through
      molecular surveys. Rats were divided into six groups: Group I and II were exposed
      to low and high frequency of PEMF (LF and HF, respectively). Group III and IV
      underwent induced disc degeneration and were exposed to low and high frequency of
      PEMF (LF/IDD and HF/IDD, respectively). Group V underwent induced disc
      degeneration (IDD), and group VI was control. The values of caspase 3, Bax, Bcl-2
      and beta-actin band density, as cell apoptotic markers, were obtained from band
      densitometry. Our results showed that the value of cleaved caspase-3 of cells and
      Bax/Bcl-2 ratio in IDD group increased significantly compared to the control
      group (p < 0.001). The value of cleaved caspase-3 and Bax/Bcl-2 ratio decreased
      significantly in LF/IDD and HF/IDD groups compared to IDD group (p < 0.05). No
      significant increase was seen in the cell apoptotic markers in the groups just
      exposed to PEMF compared to the control group. There was also no significant
      decrease in the Bax/Bcl-2 ratio in HF/IDD and LF/IDD groups compared to the
      control group. These data suggest that PEMF attenuates degenerative processes in
      rat's intervertebral discs and has no effect on normal discs. Regulations of the
      expression of apoptotic proteins may be one of the mechanisms by which PEMF is
      effective in reduce disc degeneration.

PMID- 24131392
TI  - Exposure systems for bioelectromagnetic experiments.
AB  - One of the most interesting questions in bioelectromagnetics is why there is a
      difference between results of experiments performed in various labs in
      "identical" conditions. One of the possible reasons is the difference of
      investigated objects, especially while performing experiments in vivo. However,
      the authors, as engineers, would like to focus readers' attention on the
      technical aspects of exposure systems, especially the presence and role of mutual
      interaction between biological objects under test (OUT) and the exposure system,
      the interactions between the objects, the role of polarization, the similarity of
      real exposure to that applied in experiments etc. All these factors may alter the
      results of experiments and lead to false conclusions.

PMID- 24131393
TI  - Short-duration exposure to radiofrequency electromagnetic radiation alters the
      chlorophyll fluorescence of duckweeds (Lemna minor).
AB  - Plants growing in natural environments are exposed to radiofrequency
      electromagnetic radiation (EMR) emitted by various communication network base
      stations. The environmental concentration of this radiation is increasing rapidly
      with the congested deployment of base stations. Although numerous scientific
      studies have been conducted to investigate the effects of EMR on the physiology
      of humans and animals, there have been few attempts to investigate the effects of
      EMR on plants. In this study, we attempted to evaluate the effects of EMR on
      photosynthesis by investigating the chlorophyll fluorescence (ChF) parameters of
      duckweed fronds. During the experiment, the fronds were tested with 2, 2.5, 3.5,
      5.5 and 8 GHz EMR frequencies, which are not widely studied even though there is
      a potentially large concentration of these frequencies in the environment. The
      duckweed fronds were exposed to EMR for 30 min, 1 h and 24 h durations with
      electric field strength of 45-50 V/m for each frequency. The results indicated
      that exposure to EMR causes a change in the non-photochemical quenching of the
      duckweeds. The changes varied with the frequency of the EMR and were time-varying
      within a particular frequency. The temperature remained unchanged in the duckweed
      fronds upon exposure to EMR, which confirms that the effect is non-thermal.

PMID- 24131394
TI  - Extremely low-frequency magnetic fields of transformers and possible biological
      and health effects.
AB  - Physiological processes in organisms can be influenced by extremely low-frequency
      (ELF) electromagnetic energy. Biological effect studies have great importance; as
      well as measurement studies since they provide information on the real exposure
      situations. In this study, the leakage magnetic fields around a transformer were
      measured in an apartment building in Kucukcekmece, Istanbul, and the measurement
      results were evaluated with respect to the international exposure standards. The
      transformer station was on the bottom floor of a three-floor building. It was
      found that people living and working in the building were exposed to ELF magnetic
      fields higher than the threshold magnetic field value of the International Agency
      for Research on Cancer (IARC). Many people living in this building reported
      health complaints such as immunological problems of their children. There were
      child-workers working in the textile factories located in the building. Safe
      distances or areas for these people should be recommended. Protective measures
      could be implemented to minimize these exposures. Further residential exposure
      studies are needed to demonstrate the exposure levels of ELF magnetic fields.
      Precautions should, therefore, be taken either to reduce leakage or minimize the
      exposed fields. Shielding techniques should be used to minimize the leakage
      magnetic fields in such cases.

PMID- 24131395
TI  - Involvement of NMDA receptor in low-frequency magnetic field-induced anxiety in
      mice.
AB  - It had been reported that exposure to extremely low-frequency magnetic field
      (ELFMF) induces anxiety in human and rodents. Anxiety mediates via the activation
      of N-methyl-d-aspartate (NMDA) receptor, whereas activation of gamma-aminobutyric
      acid (GABA) receptor attenuates the same. Hence, the present study was carried
      out to understand the contribution of NMDA and/or GABA receptors modulation in
      ELFMF-induced anxiety for which Swiss albino mice were exposed to ELFMF (50 Hz,
      10 G) by subjecting them to Helmholtz coils. The exposure was for 8 h/day for 7,
      30, 60, 90 and 120 days. Anxiety level was assessed in elevated plus maze, open
      field test and social interaction test, on 7th, 30th, 60th, 90th and 120th
      exposure day, respectively. Moreover, the role of GABA and glutamate in ELFMF
      induced anxiety was assessed by treating mice with muscimol [0.25 mg/kg
      intraperitoneally (i.p.)], bicuculline (1.0 mg/kg i.p.), NMDA (15 mg/kg i.p.) and
      MK-801 (0.03 mg/kg i.p.), as a GABAA and NMDA receptor agonist and antagonist,
      respectively. Glutamate receptor agonist exacerbated while inhibitor attenuated
      the ELFMF-induced anxiety. In addition, levels of GABA and glutamate were
      determined in regions of the brain viz, cortex, striatum, hippocampus and
      hypothalamus. Experiments demonstrated significant elevation of GABA and
      glutamate levels in the hippocampus and hypothalamus. However, GABA receptor
      modulators did not produce significant effect on ELFMF-induced anxiety and
      elevated levels of GABA at tested dose. Together, these findings suggest that
      ELFMF significantly induced anxiety behavior, and indicated the involvement of
      NMDA receptor in its effect.

PMID- 24131398
TI  - Magnetic circular dichroism spectroscopy of N-confused porphyrin and its ionized
      forms.
AB  - N-Confused porphyrin (NCP) and its externally methylated variant (MeNCP) were
      investigated using UV-vis and magnetic circular dichrosim (MCD) spectroscopies.
      In addition to evaluating the spectroscopy of the neutral compounds, the
      acid/base chemistry of these macrocycles was examined by the same methods. NCP
      exhibits two tautomeric states depending on the polarity of the solvent, and
      their protonation/deprotonation chemistries also differ depending on solvent
      polarity. DFT and TDDFT calculations were employed to evaluate the observed
      spectroscopic changes. Using both experimental and calculated results, we were
      able to determine the sites of protonation/deprotonation for both tautomeric
      forms of NCP. Inspection of the MCD Faraday B terms for all of the macrocycles
      presented in this report showed that the DeltaHOMO > DeltaLUMO condition is
      maintained in all cases, and these observations were in good agreement with the
      DFT calculations. 

PMID- 24131397
TI  - Maintaining distinctions under threat: heterosexual men endorse the biological
      theory of sexuality when equality is the norm.
AB  - According to social identity theory, group members sometimes react to threats to
      their group's distinctiveness by asserting the distinctiveness of their group. In
      four studies (n = 261) we tested the hypothesis that heterosexual men with a
      greater propensity to be threatened by homosexuality would react to egalitarian
      norms by endorsing biological theories of sexuality. Heterosexual men, but not
      women, with narrow prototypes of their gender in-group endorsed biological
      theories the most (Study 1). Heterosexual men with higher gender self-esteem,
      with heterosexist attitudes, who endorsed traditional gender roles, and with
      narrow prototypes of their gender in-group, endorsed the biological theories more
      when egalitarian norms rather than anti-egalitarian norms (Studies 2 and 3) or
      pro-minority ideologies that emphasized group differences (Study 4) were made
      salient. These findings show group-level reactive distinctiveness among members
      of a high-status group in a context of threat to the unique privileges that they
      once enjoyed. 

PMID- 24131399
TI  - Added value of multiplex Luminex Gastrointestinal Pathogen Panel (xTAG(r) GPP)
      testing in the diagnosis of infectious gastroenteritis.
AB  - The Luminex Gastrointestinal Pathogen Panel (xTAG((r)) GPP) detects in one assay
      the most common gastroenteritis-causing pathogens and toxins, namely adenovirus
      40/41, norovirus genogroup (NG) I/II, rotavirus A, Clostridium difficile toxin
      A/B, Campylobacter sp., Escherichia coli O157, Enterotoxigenic E. coli heat
      labile enterotoxin/heat-stable enterotoxin, Salmonella sp., Shiga-toxin producing
      E. coli, Shiga-like toxin (Stx)1/2, Shigella sp., Vibrio cholerae, Yersinia
      enterocolitica, Cryptosporidium sp., Entamoeba histolytica and Giardia sp. In
      this study, we compared the results that were obtained by testing 393 faecal
      samples, collected during November and December 2011 at our laboratory, using the
      xTAG((r)) GPP assay with the results of the routine diagnostic procedure. This
      procedure includes culture for bacteria and real-time PCR for viruses and
      parasites, but only if the test was requested by the clinician. If the clinician
      did not request the test for an xTAG((r)) GPP-positive target, real-time PCR
      assays were used to confirm xTAG((r)) GPP positivity. Discrepant results were
      also tested with real-time PCR assays. A total of 83 targets were detected in 76
      samples using xTAG((r)) GPP. The xTAG((r)) GPP assay detected 43 additional
      positives compared with the routine diagnostic procedure, of which 11 targets
      could not be confirmed by real-time PCR. The non-confirmed targets were
      Campylobacter (one sample), Salmonella (four samples), Shigella (one sample) and
      E. histolytica (five samples). The xTAG((r)) GPP was shown to be a convenient and
      sensitive assay for detection of 15 major gastrointestinal pathogens in a single
      molecular test, but for detection of E. histolytica and Salmonella, a
      confirmatory assay is indicated.

PMID- 24131400
TI  - Stalking experiences and associated factors--a controlled population-based study
      from Norway.
AB  - BACKGROUND: Stalking is a considerable health problem. In order to develop
      interventions for victims, more knowledge is needed concerning prevalence, stress
      and coping related to stalking as well as associated symptomatology in the
      victims. This is the first population-based study of stalking in Norway. AIMS: To
      examine the prevalence of stalking in relation to gender and time, and the
      association with indicators of socio-demographic status and mental health.
      METHODS: A cross-sectional case-control questionnaire design. The sample, 5000
      Norwegians aged 20-59 years, was nationally representative according to gender,
      10-year age groups and county of living. A total of 248 (5%) of the mailed
      envelops were returned due to wrong address, leaving 4752 individuals as possible
      respondents. Among them 1520 (32%) returned the questionnaire, but 98 of them had
      to be discarded due to lack of completion, giving a sample of 1422 valid
      questionnaires (30%). RESULTS: The total weighted lifetime prevalence of stalking
      was 8.1% (95% CI 6.6-9.4%), for females 11.8% (95% CI 10.2-13.5%) and for males
      4.3% (95% CI 3.2-5.3%) [corrected]. The point prevalence of current stalking was
      2.8% (95% CI 2.0-3.7%). The stalked individuals had a significantly poorer social
      situation and mental health than the controls. Few significant group differences
      were observed between males and females exposed to stalking. CONCLUSIONS: The
      prevalence of stalking was within the range observed by questionnaire studies in
      other cultures.

PMID- 24131401
TI  - Synthesis of dienyl ketones via palladium(II)-catalyzed direct cross-coupling
      reactions between simple alkenes and vinyl ketones: application to the synthesis
      of vitamin A1 and bornelone.
AB  - An efficient and general method for the synthesis of conjugated dienyl ketones
      via palladium(II) acetate catalyzed direct cross-coupling between simple alkenes
      and vinyl ketones is reported. This method has been successfully applied for the
      synthesis of Vitamin A1 and bornelone. 

PMID- 24131402
TI  - Increased frequency of intestinal CD4+ T cells reactive with mycobacteria in
      patients with Crohn's disease.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of mycobacteria and
      Escherichia coli reactive T cells in intestinal biopsies from patients with
      Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: The
      biopsies were obtained by colonoscopy from adult patients with active CD (n = 5)
      and active UC (n = 4). The number of CD4+ T cell clones expanded and screened
      from each patient varied from 383 to 3972 giving a total of 16639 individual
      clones. The T cell clones were tested for responses to Mycobacterium avium
      subspecies paratuberculosis (MAP) and E. coli. The cytokine profile of 42
      individual T cell clones from four CD patients was assessed. RESULTS: The
      frequency of mycobacteria reactive T cell clones in CD patients ranged from 0.17
      to 1.63% and was higher (p = 0.038) than the frequency of E. coli reactive T
      cells ranging from 0 to 0.18%. No or very low numbers of mycobacteria reactive
      clones were detected in three UC patients while the fourth UC patient had a
      frequency similar to what was observed in CD patients. The frequencies of E. coli
      reactive T cell clones in UC patients ranged from 0 to 0.52%. T cell clones (n =
      42) from CD patients all produced IL-17 and/or IFN-gamma. Several clones were
      also able to produce IL-10. CONCLUSIONS: The high frequency of intestinal tissue
      resident T cells reactive to mycobacteria suggests that an adaptive immune
      response have taken place and argues that these bacteria may contribute to the
      chronic inflammation in CD.

PMID- 24131403
TI  - Anti-coagulation, anti-platelets or no therapy in haemodialysis patients with
      atrial fibrillation: A decision analysis.
AB  - BACKGROUND: Optimal treatment of atrial fibrillation (AF) in the haemodialysis
      population is uncertain due to the exclusion of this group from randomized
      trials. The risk-benefit profile for anticoagulation and anti-platelet therapy in
      haemodialysis differs from the general population due to platelet dysfunction
      from uraemia, altered pharmacokinetics and increased falls risk. METHODS: This
      decision analysis used a Markov-state transition model that took a patient
      perspective over a 5 year timeframe. The Markov model compared life-years gained
      and quality-adjusted life-years gained (QALY) for three AF treatment strategies:
      warfarin, aspirin and no treatment. The base case was a 70-year-old man on
      haemodialysis with non-valvular AF. RESULTS: In the base case, the total health
      outcomes in life-years and QALY were 2.37 and 1.47 respectively for warfarin,
      2.38 and 1.61 respectively for aspirin, and 2.39 and 1.61 respectively for no
      treatment. Thus, warfarin led to 0.14 fewer QALY or 1.7 fewer months of life
      lived in full health, compared with either aspirin or no therapy. The finding
      that warfarin generated the lowest expected QALY was robust to one-way, two-way
      and probabilistic sensitivity analyses. CONCLUSIONS: Our results suggest that
      warfarin should not be the default choice for older haemodialysis patients with
      non-valvular AF as it provides the fewest QALY compared with aspirin or no
      therapy.

PMID- 24131406
TI  - Analgesic Effect of Light-Emitting Diode (LED) Therapy at Wavelengths of 635 and
      945 nm on Bothrops moojeni Venom-Induced Hyperalgesia.
AB  - Envenoming induced by Bothrops snakes is characterized by drastic local tissue
      damage involving hemorrhage, myonecrosis and proeminent inflammatory and
      hyperalgesic response. The most effective treatment is antivenom therapy, which
      is ineffective in neutralizing the local response. Herein, it was evaluated the
      effectiveness of light-emitting diode (LED) at wavelengths of 635 and 945 nm in
      reducing inflammatory hyperalgesia induced by Bothrops moojeni venom (BmV) in
      mice, produced by an subplantar injection of BmV (1 MUg). Mechanical hyperalgesia
      and allodynia were assessed by von Frey filaments at 1, 3, 6 and 24 h after venom
      injection. The site of BmV injection (1.2 cm(2) ) was irradiated by LEDs at 30
      min and 3 h after venom inoculation. Both 635 nm (110 mW, fluence of 3.76 J/cm(2)
      and 41 s of irradiation time) and 945 nm (120 mW, fluence of 3.8 J/cm(2) and 38 s
      of irradiation time) LED inhibited mechanical allodynia and hyperalgesia of mice
      alone or in combination with antivenom treatment, even when the symptoms were
      already present. The effect of phototherapy in reducing local pain induced by BmV
      should be considered as a novel therapeutic tool for the treatment of local
      symptoms induced after bothropic snake bites.

PMID- 24131407
TI  - Asphaltene adsorption onto acidic/basic metal oxide nanoparticles toward in situ
      upgrading of reservoir oils by nanotechnology.
AB  - The effects of surface acidity and basicity of metal oxide nanoparticles on the
      thermodynamics of asphaltene adsorption were studied. Three different categories
      of metal oxides/salts with acidic (WO3 and NiO), amphoteric (Fe2O3 and ZrO2), and
      basic (MgO and CaCO3) surfaces were synthesized, and their textural, structural,
      and acid-base properties were characterized. Asphaltenes were extracted from a
      dead oil sample and characterized by X-ray powder diffraction and Fourier
      transform infrared spectroscopy. The acid and base numbers of the asphaltenes
      were measured. The nanoparticles were added to the asphaltene-toluene solutions,
      and the amount of adsorbed asphaltene was obtained through centrifugation
      followed by UV-vis spectroscopy of the supernatant liquid and temperature
      programmed oxidation analysis of the precipitated solid. The concentrations of
      organic acid and base groups in the asphaltenes are 2.75 and 12.34 mg of KOH/g,
      respectively, indicating that the asphaltenes are more basic in nature. Isotherms
      of the asphaltene adsorption onto the six metal oxides/salts fit the Langmuir
      model closely. The asphaltene adsorption capacity of the nanoparticles is 1.23
      3.67 mg/m(2) and decreases in the order of NiO > Fe2O3 > WO3 > MgO > CaCO3 >
      ZrO2, concomitant with the synergetic effects of acidity and the net charge of
      the surfaces. High-resolution transmission electron microscopy illustrates that
      the asphaltenes are spread out over the surfaces with no short-range/long-range
      order. The adsorption of the asphaltenes onto the six samples is exothermic and
      spontaneous with the Gibbs energy change of -27.80 to -28.79 kJ/mol at 25 
      degrees C. The absolute value of the enthalpy change of the adsorption is
      calculated to be within the range of 5-20 kJ/mol. Acid-base interaction and
      electrostatic attraction seem to be the dominant forces contributing to the
      adsorption of the asphaltenes onto the metal oxide/salt surfaces. 

PMID- 24131405
TI  - High capacity nanoporous silicon carrier for systemic delivery of gene silencing
      therapeutics.
AB  - Gene silencing agents such as small interfering RNA (siRNA) and microRNA offer
      the promise to modulate expression of almost every gene for the treatment of
      human diseases including cancer. However, lack of vehicles for effective systemic
      delivery to the disease organs has greatly limited their in vivo applications. In
      this study, we developed a high capacity polycation-functionalized nanoporous
      silicon (PCPS) platform comprised of nanoporous silicon microparticles
      functionalized with arginine-polyethyleneimine inside the nanopores for effective
      delivery of gene silencing agents. Incubation of MDA-MB-231 human breast cancer
      cells with PCPS loaded with STAT3 siRNA (PCPS/STAT3) or GRP78 siRNA (PCPS/GRP78)
      resulted in 91 and 83% reduction of STAT3 and GRP78 gene expression in vitro.
      Treatment of cells with a microRNA-18a mimic in PCPS (PCPS/miR-18) knocked down
      90% expression of the microRNA-18a target gene ATM. Systemic delivery of
      PCPS/STAT3 siRNA in murine model of MDA-MB-231 breast cancer enriched particles
      in tumor tissues and reduced STAT3 expression in cancer cells, causing
      significant reduction of cancer stem cells in the residual tumor tissue. At the
      therapeutic dosage, PCPS/STAT3 siRNA did not trigger acute immune response in FVB
      mice, including changes in serum cytokines, chemokines, and colony-stimulating
      factors. In addition, weekly dosing of PCPS/STAT3 siRNA for four weeks did not
      cause signs of subacute toxicity based on changes in body weight, hematology,
      blood chemistry, and major organ histology. Collectively, the results suggest
      that we have developed a safe vehicle for effective delivery of gene silencing
      agents. 

PMID- 24131408
TI  - UV-induced alterations of the skin evaluated over time by reflectance confocal
      microscopy.
AB  - BACKGROUND: Ultraviolet radiation (UVR) induces various alterations of the skin
      and plays a decisive part regarding the development of melanoma and non-melanoma
      skin cancer. For a closer examination of these phenomena in vivo reflectance
      confocal microscopy (RCM) is one of the most eligible options as it represents a
      diagnostic tool that allows a non-invasive examination of the skin, showing
      microanatomical structures and individual cells. OBJECTIVES: The aim of this
      study was using RCM to observe alterations of the skin induced by UVR and to
      describe the development of these changes. In addition, the findings were
      compared with histological examinations of the same area. METHODS: A small area
      in the gluteal region of 10 healthy subjects was exposed to a threefold
      individual minimal erythema dose of solar-simulated UVR. The following
      development of the sunburn reaction was evaluated with RCM 1, 24, 72 h and 1 week
      after UVR exposure. Furthermore, RCM images of unexposed skin were obtained,
      serving as a reference. To contrast histological examination with RCM, punch
      biopsies were performed at each point in time. The obtained data were interpreted
      regarding histological and RCM-based criteria on sunburn reaction. RESULTS: All
      important UVR-induced alterations of the skin could be shown in RCM beginning
      with an inflammatory reaction (inflammatory cells, vasodilatation, oedema),
      containing the formation of microvesicles, followed by the appearance of
      apoptotic keratinocytes (sunburn cells), activated melanocytes and at last, loss
      of the epidermal structure. There was an excellent correlation between RCM and
      histological features. CONCLUSIONS: Reflectance confocal microscopy is a highly
      valuable tool for non-invasive monitoring of UVR-induced changes of the skin over
      time. Furthermore, RCM provides a more detailed visualization of inflammatory
      cell formation and epidermal blood flow than histological examination can.

PMID- 24131409
TI  - The global outlook for dementia.

PMID- 24131410
TI  - PTSD in psychiatric nurses and other mental health providers: a review of the
      literature.
AB  - Psychiatric nurses are subject to a high rate of assault by patients. The stress
      of exposure to assault and the potential for assault appear to impact nurses'
      emotional states in the form of post-traumatic stress and post-traumatic stress
      disorder (PTSD). Most studies report a prevalence rate of PTSD in this population
      of between 9-10%. Training in the management of aggressive patients,
      participating in Critical Incident Debriefing, and having routine structured
      debriefing meetings may play a role in facilitating the development of resilience
      in nurses with respect to the risk of PTSD. Knowledge about the state of the
      science regarding aggression and PTSD is necessary for clinicians and researchers
      to develop and test effective strategies. This article presents a review of the
      current literature on this topic. 

PMID- 24131411
TI  - Latino young men and health promotion, emerging adulthood, and acculturation: a
      qualitative exploration.
AB  - The purpose of this qualitative study was to identify factors that influenced
      health promotion behaviors in young Latino men. The participants consisted of 16
      Latino men between the ages of 18 and 25 who were attending a Hispanic-serving
      academic institution. The respondents were asked to participate in an individual
      interview and focus group interview. The findings of this study indicate that
      respondents were concerned with love, work, and the multiple worlds they
      inhabited. They were influenced by both their Latino ethnicity as well as their
      inability to access the health care system. The qualitative findings may provide
      some important insights into the lived experience of these Latino young men. 

PMID- 24131412
TI  - "It was pretty scary": the theme of fear in young adult women's descriptions of a
      history of adolescent dating abuse.
AB  - The mental health impact of abusive adolescent dating relationships has not been
      well described, but fear related to abuse has been reported. We elaborate the
      theme of fear in women's descriptions of a history of adolescent dating abuse. A
      sample of community-based women, ages 19-34, who experienced an abusive dating
      relationship during adolescence (ages 11-20) was used. Data were analyzed via
      thematic analysis. Fear was a consistent and resonant theme. Three types of fear
      were identified: fear for self, fear for other relationships, and fearful
      expectation. These results offer important insights into the impact of abusive
      adolescent relationships on women's mental health. 

PMID- 24131413
TI  - The importance of communication for clinical leaders in mental health nursing:
      the perspective of nurses working in mental health.
AB  - Communication has been identified as an important attribute of clinical
      leadership in nursing. However, there is a paucity of research on its relevance
      in mental health nursing. This article presents the findings of a grounded theory
      informed study exploring the attributes and characteristics required for
      effective clinical leadership in mental health nursing, specifically the views of
      nurses working in mental health about the importance of effective communication
      in day to day clinical leadership. In-depth interviews were conducted to gain
      insight into the participants' experiences and views on clinical leadership in
      mental health nursing. The data that emerged from these interviews were
      constantly compared and reviewed, ensuring that any themes that emerged were
      based on the participants' own experiences and views. Participants recognized
      that effective communication was one of the attributes of effective clinical
      leadership and they considered communication as essential for successful working
      relationships and improved learning experiences for junior staff and students in
      mental health nursing. Four main themes emerged: choice of language;
      relationships; nonverbal communication, and listening and relevance. Participants
      identified that clinical leadership in mental health nursing requires effective
      communication skills, which enables the development of effective working
      relationships with others that allows them to contribute to the retention of
      staff, improved outcomes for clients, and the development of the profession. 

PMID- 24131414
TI  - Cross-cultural caregiving and the temporal dimension.
AB  - The caregiving research literature has explored and documented findings from
      psychological, clinical, and policy/program perspectives, but little is known
      regarding the contextual perspectives of caregiving. Temporal factors influence
      the structure and functioning of the caregiving family. The proposed paradigm
      adaptation extends a contextual perspective that addresses the exploration of the
      caregiving process as a temporal, dynamic, progressive process over time, in
      which decisions made by caregivers may not always be based on observable tasks
      but, nevertheless, may have important consequences. When cultures cross,
      attitudes and behaviors are modified, resulting from contact with a different set
      of values and beliefs. Cross-cultural research aims to explore these changes that
      take place over time. Future research should consider the inclusion of measures
      that assess the temporal aspect of caregiving and the acculturation
      considerations of family caregivers. These measures are especially needed because
      of the increased influence of international migration, economic globalization,
      and political conflicts in today's multicultural societies. 

PMID- 24131415
TI  - "The second thing to hell is living under that bridge": narratives of women
      living with victimization, serious mental illness, and in homelessness.
AB  - The increasing rates of violence committed against homeless women living with
      serious mental illness (SMI) have been well documented. These increasing rates of
      violence need attention as they are a serious public health concern. The purpose
      of this qualitative study is to increase our understanding of victimization among
      this population as perceived by those who have lived the experience. The study
      sample consists of 15 homeless adult women who self-reported having been
      diagnosed with a SMI. The findings highlight the reality that, provided with the
      right type of resources, positive growth can occur among these women despite
      lifelong events of trauma, victimization, and loss. 

PMID- 24131416
TI  - Antipsychotic options for delirium-related agitation--a multidisciplinary
      practitioner survey.

PMID- 24131417
TI  - Valuing imagination.

PMID- 24131418
TI  - "Cultural cognition": what mental health researchers and clinicians might learn
      from the climate change debate.

PMID- 24131420
TI  - Design of novel potent inhibitors of human uridine phosphorylase-1: synthesis,
      inhibition studies, thermodynamics, and in vitro influence on 5-fluorouracil
      cytotoxicity.
AB  - Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused
      by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses
      of Urd are required to achieve a protective effect against 5-FU toxicity, but
      exogenous administration of Urd is not well-tolerated. Selective inhibitors of
      human uridine phosphorylase (hUP) have been proposed as a strategy to increase
      Urd levels. We describe synthesis and characterization of a new class of ligands
      that inhibit hUP type 1 (hUP1). The design of ligands was based on a possible SN1
      catalytic mechanism and as mimics of the carbocation in the transition state of
      hUP1. The kinetic and thermodynamic profiles showed that the ligands here
      presented are the most potent in vitro hUP1 inhibitors developed to date. In
      addition, a lead compound improved the antiproliferative effects of 5-FU on colon
      cancer cells, accompanied by a reduction of in vitro 5-FU cytotoxicity in
      aggressive SW-620 cancer cells. 

PMID- 24131421
TI  - An interprofessional educational approach to oral health care in the geriatric
      population.
AB  - An interprofessional educational approach was used to provide five in-service
      training sessions for all direct health care providers in a long-term care
      facility, and one half-day seminar/live webinar for community-licensed health
      care professionals. Content included presentations by five disciplines: (a)
      periodontist: oral-systemic relationship, (b) oral pathologist: oral pathology,
      (c) pharmacist: oral health-pharmacological link, (d) dietitian: oral health
      dietary link, and (e) occupational therapist: providing and practicing proper
      oral hygiene. Significant improvement in posttest scores for the five in-service
      training sessions and the half-day seminar/live webinar was revealed in t-test
      results, representing an increase in knowledge gained. Approximately 80% of the
      145 participants indicated that they would make a change in patient care.
      Findings indicate that the in-service training sessions and half-day seminar/live
      webinar supported development of the geriatric work force by utilizing an
      interprofessional educational approach which will assist in meeting the oral
      health care needs of the geriatric population. 

PMID- 24131422
TI  - The MM-CGI Cerebral Palsy: modification and pretesting of an instrument to
      measure anticipatory grief in parents whose child has cerebral palsy.
AB  - AIMS AND OBJECTIVES: To establish the potential of a modified version of the MM
      CGI Childhood Cancer to assess anticipatory grief in parents of children with
      cerebral palsy, to amend the existing scale for use with the specific patient
      group, to test the psychometric properties of the modified version (MM-CGI
      Cerebral Palsy) and to review the clinical potential of the new scale.
      BACKGROUND: Parents of children with cerebral palsy may experience reactions
      similar to parents of children with other enduring or life-limiting conditions,
      and anticipatory grief may be one such psychological reaction. While the burden
      of caring is sometimes balanced by positive perceptions of the child, which
      enhance coping ability, for many parents the outcome is damage to their physical
      and mental health and impaired family functioning. DESIGN: A cross-sectional,
      descriptive, correlational design. METHODS: The MM-CGI Cerebral Palsy was
      administered in structured interviews with 204 parents. Standardised measures of
      caregivers' depression, stress and perceived social support were also
      administered. Mothers and fathers were recruited from healthcare centres and
      schools for special education. Cronbach's alpha was used to assess internal
      consistency, and Pearson's product-moment correlation was used to assess
      construct validity. RESULTS: The subscales were each found to measure a single
      dimension of anticipatory grief, and significant correlations were established
      with existing instruments. The instrument demonstrated excellent internal
      consistency reliability and good construct validity. CONCLUSIONS: The MM-CGI
      Cerebral Palsy could be useful for diagnosing anticipatory grief among parents of
      children with cerebral palsy. This preliminary work moves the programme on to
      testing in intervention studies. RELEVANCE TO CLINICAL PRACTICE: In the absence
      of an existing measure for the assessment of anticipatory grief, specifically in
      parents of children with cerebral palsy, the MM-CGI Cerebral Palsy could prove to
      be an effective assessment tool for clinicians and researchers.

PMID- 24131423
TI  - Cerebrospinal fluid penetration of tigecycline.
AB  - We report, in a clinical setting, the tigecycline concentration and area under
      the concentration-time curve (AUC) - both in blood and in cerebrospinal fluid
      (CSF) - of a patient with a ventriculo-atrial shunt infection. Tigecycline weakly
      penetrates CSF the CSF-to-serum concentration ratio was 0.079 and CSF-to-serum
      AUC(0-12) ratio was 0.067.

PMID- 24131424
TI  - Cigarette smoking is associated with increased diastolic blood pressure among
      Chinese nonagenarians/centenarians.
AB  - OBJECTIVE: Cigarette smoking has been confirmed as a factor influencing arterial
      blood pressure. In the present study, we studied whether cigarette smoking habits
      were still associated with arterial blood pressure among Chinese
      nonagenarians/centenarians. METHODS: The present study analyzed data from a
      survey conducted on all residents aged 90 years or more in the DuJiangYan
      district (in total 2,311,709 inhabitants) in 2005. RESULTS: The individuals
      included in the statistical analysis were 216 men and 445 women. Individuals who
      were heavy smokers (76.62 +/- 13.28 mmHg) had higher diastolic blood pressure,
      compared with medium and light smokers (72.33 +/- 12.98 and 70.28 +/- 10.31 mmHg)
      (F = 3.551, p = 0.030). There was a higher prevalence of diastolic hypertension
      (21.62% vs 5.75% and 7.14%, chi(2 =) 6.302, p = 0.043). Furthermore, there was a
      higher risk for diastolic hypertension in heavy smokers (OR = 3.886, 95% CI 1.241
      12.161) (adjusted) compared with medium (OR = 1.475, 95% CI 0.599-3.360) and
      light smokers (1.00 reference). There was, however, no significant difference in
      systolic blood pressure or prevalence of systolic hypertension among the
      different smoking groups. CONCLUSIONS: In summary, we found that among Chinese
      nonagenarians/centenarians, heavy smoking (current or former) could increase
      diastolic blood pressure and prevalence of diastolic hypertension, but was not
      associated with changes in systolic blood pressure.

PMID- 24131425
TI  - Palladium-catalyzed phosphonylation: synthesis of C3-, C4-, and C5-phosphonylated
      pyrazoles.
AB  - A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H
      phosphonates, H-phosphinates, and secondary phosphine oxides has been developed.
      This coupling reaction constitutes the first general method allowing the
      introduction of a great diversity of phosphorus substituents on the different
      carbons of the pyrazole ring in a one-step process. 

PMID- 24131426
TI  - Development of an immuno-based colorimetric assay for white spot syndrome virus.
AB  - White spot syndrome virus (WSSV) is a major cause of infectious disease in
      cultured shrimp. A fast and reliable method for detecting and monitoring the
      amount of WSSV during farming would be extremely useful. This work describes a
      sandwich immunoassay that uses anti-GST-VP26, a WSSV-binding protein (WBP), and
      modified streptavidin magnesphere paramagnetic particles (SMPPs) to develop the
      technique. The WBP was immobilized on SMPPs and later bound to different copies
      of WSSV. The binding was detected using anti-GST-VP26 conjugated to alkaline
      phosphatase. This enzymatic reaction successfully changed the test solution to a
      concentration-dependent yellow color that was measured at 405 nm. The sensitivity
      of this method was between 1.6 * 10(4) and 1.6 * 10(7) copies uL(-1) of WSSV. In
      this study, the color for detection and semiquantitative analysis is easily
      observed and measured and can lead to the development of a test kit for screening
      WSSV during shrimp farming. 

PMID- 24131427
TI  - Enhanced chemical reactivity of graphene induced by mechanical strain.
AB  - Control over chemical reactivity is essential in the field of nanotechnology.
      Graphene is a two-dimensional atomic sheet of sp(2) hybridized carbon with
      exceptional properties that can be altered by chemical functionalization. Here,
      we transferred single-layer graphene onto a flexible substrate and investigated
      the functionalization using different aryl diazonium molecules while applying
      mechanical strain. We found that mechanical strain can alter the structure of
      graphene, and dramatically increase the reaction rate, by a factor of up to 10,
      as well as increase the final degree of functionalization. Furthermore, we
      demonstrate that mechanical strain enables functionalization of graphene for both
      p- and n-type dopants, where unstrained graphene showed negligible reactivity.
      Theoretical calculations were also performed to support the experimental
      findings. Our findings offer a simple approach to control the chemical reactivity
      of graphene through the application of mechanical strain, allowing for a tuning
      of the properties of graphene. 

PMID- 24131428
TI  - Development of the EUCAST disk diffusion antimicrobial susceptibility testing
      method and its implementation in routine microbiology laboratories.
AB  - With the support of ESCMID and European countries, EUCAST has developed a disk
      diffusion test with zone diameter breakpoints correlated with the EUCAST clinical
      MIC breakpoints. The development of the EUCAST disk diffusion method and quality
      control criteria are described, together with guidance on quality control and
      implementation of the method in clinical microbiology laboratories. The method
      includes the use of Mueller-Hinton agar without supplements for non-fastidious
      organisms and with 5% mechanically defibrinated horse blood and 20 mg/L beta-NAD
      for fastidious organisms, a standardized inoculum resulting in confluent growth,
      an incubation time of 16-20 h, a reading guide on how to read zone diameters on
      individual species-agent combinations and zone diameter breakpoints calibrated to
      the EUCAST clinical MIC breakpoints. EUCAST recommendations are described in
      detail and updated regularly on the EUCAST website (http://www.eucast.org).

PMID- 24131430
TI  - Use of the International Classification of Functioning, Disability and Health as
      a framework for analyzing the Stroke Impact Scale-16 relative to falls.
AB  - OBJECTIVE: To determine if subscores based on grouping Stroke Impact Scale 16
      (SIS-16) items according to International Classification of Functioning, Health
      and Disability (ICF) components are more accurate in identifying individuals with
      a history of falls than the total SIS-16 score. DESIGN: Case series. SUBJECTS: 43
      community-dwelling people with chronic stroke. METHODS: Participants were grouped
      based on six month fall history (no fall versus one or more falls). The SIS-16
      items were categorized as belonging to the Body Structure and Function (BSF),
      Activity (ACT) or Participation (PART) component of the ICF. SIS-16 total score
      and ICF component subscores were analyzed for their association with falls.
      Receiver Operating Characteristic Curves were (ROC) analyzed. RESULTS: There were
      significant differences between groups on SIS-16 total (p = 0.006), BSF (p =
      0.041) and ACT (p = 0.003) scores. The BSF and ACT component subscores had the
      highest specificity (0.91) and sensitivity (0.80), respectively, for categorizing
      participants according to fall history. The BSF + ACT component subscore
      demonstrated greater accuracy than the total SIS-16 for identifying people with
      falls (area under the curve = 0.78). CONCLUSION: The ICF may be a useful model
      for analysis of fall screening tools for people with chronic stroke. ICF
      component subscores are more accurate than the SIS-16 total score for this
      purpose.

PMID- 24131431
TI  - Fabrication of ordered ZnO/TiO2 heterostructures via a templating technique.
AB  - Two kinds of ordered ZnO/TiO2 heterostructures were fabricated via a facile
      approach. The architecture of the TiO2 substrate could be controlled by
      alternating the filling forms of the template, and the morphology of the
      secondary ZnO nanostructure could be further tuned by adjusting the parameters of
      the hydrothermal reaction. Then two different morphologies of ZnO/TiO2
      heteroarchitectures with ZnO nanorods and nanoplates growing on TiO2 shells and
      bowls were successfully achieved, respectively. 

PMID- 24131432
TI  - Effects of adding urea on fermentation quality of pruned persimmon branch silage
      and its digestibility, preference, nitrogen balance and rumen fermentation in
      beef cattle.
AB  - Four cattle were used in a 4 * 4 Latin square design experiment to study
      digestibility, ruminal fermentation, nitrogen retention and preference of
      ensiling pruned persimmon branch (PPB) chips treated with urea. After 60 days of
      ensiling, urea-treated PPB showed higher (P < 0.05) pH, acetic acid and ammonia-N
      levels than no-urea PPB. Both urea-treated PPB and rice straw diets showed higher
      (P < 0.05) apparent digestibility and digestible nutrient content in cattle than
      no-urea PPB diet. Neither mold nor yeast was detected in any urea-treated PPB.
      Urinary and fecal excretion as well as nitrogen retention in cattle fed urea
      treated PPB were higher (P < 0.05) than in those fed no-urea PPB and rice straw.
      With the exception that ruminal ammonia-N levels in cattle fed urea-treated PPB
      were higher (P < 0.05) than in those given no-urea PPB and rice straw, ruminal
      pH, volatile fatty acid concentrations, and the acetic : propionic acid ratio of
      rumen content were unaffected by diets. The rank order of preference was rice
      straw > low-urea > no-urea > high-urea. The results suggested that urea treatment
      of PPB inhibited growth of mold and yeast during silage storage, enhanced its
      digestibility and had nutritive value almost equivalent to that of rice straw.

PMID- 24131433
TI  - The ecological literature, an idea-free distribution.

PMID- 24131434
TI  - Mapping of zebrafish research: a global outlook.
AB  - On the basis of analysis of 17,151 records on zebrafish identified from Zebrafish
      Information Network: the zebrafish model organism database and Web of Science,
      the research performance on this model organism has been evaluated. The earliest
      research work on zebrafish as reflected in the databases goes back to 1951. After
      a rather slow growth till the 1980s, research on zebrafish gained momentum in the
      1990s. Analysis shows a rapid and consistent increase in the publication output
      with 226 publications in the year 1996, to 1929 publications in the year 2012.
      The prominent areas of zebrafish research, journals, and leading authors as
      reflected from the research output have been identified. USA is the most
      productive country with 8196 articles. The most frequently used keywords were
      also determined to gain insights about the research trends and some of the
      commonly used keywords other than zebrafish and Danio rerio are development,
      retina, and gene expression.

PMID- 24131435
TI  - The effect of paclobutrazol on the development of zebrafish (Danio rerio)
      embryos.
AB  - Paclobutrazol (PBZ), a trazole-containing fungicide, is widely used on food
      crops. Frequent usage of PBZ may contaminate water, but its toxicity to aquatic
      organisms is understudied. Although the chronic effects of PBZ exposure on
      reproductive, antioxidant defense, and liver metabolism systems in rockfish have
      been reported, the toxic effects of PBZ on aquatic embryos are unknown. Here, we
      report that PBZ disrupts the development of heart and craniofacial cartilage in
      zebrafish embryos, and decreases their survival and hatching rates. PBZ affects
      the normal process of cardiac looping, which may lead to a slower heart beat
      accompanied by pericardia edema and apoptotic myocytes. PBZ also decreases the
      population of migratory neural crest cells, which give rise to craniofacial
      cartilage. Our results reveal high embryonic toxicity of PBZ on aquatic
      organisms, and thus hold significance for the impact of fungicides on public
      health and ecology.

PMID- 24131436
TI  - Liver transplantation for HBsAg-positive recipients using grafts from HBsAg
      positive deceased donors.
AB  - This study reports our experience using deceased donor liver grafts from HBsAg
      positive donors. We performed eight cases of liver transplantation (LT) using
      grafts from deceased HBsAg-positive donors between November 2005 and October
      2010. The median age of donors was 48 years (range: 26-64). HBV DNA in the serum
      of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative.
      Preoperative laboratory and liver biopsy samples revealed the absence of
      definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive
      preoperatively except one patient with HBsAg(-) status post previous LT for HBV
      related liver cirrhosis. The median age was 60 years (range: 46-76) at LT. Post
      LT antiviral management consisted of hepatitis B immunoglobulin and antiviral
      nucleos(t)ide analogues. The median follow-up period was 25.5 months (range: 14
      82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA
      disappearance postoperatively. Three recipients died of HBV-unrelated causes. The
      remaining five recipients were stable with normal liver function and no marked
      pathologic changes on follow-up biopsies. This experience shows that LT using
      grafts from deceased HBsAg-positive donors is feasible, and may represent a
      valuable expansion of the pool of organ donors with appropriate antiviral
      management and monitoring.

PMID- 24131442
TI  - Rapid and reliable thickness identification of two-dimensional nanosheets using
      optical microscopy.
AB  - The physical and electronic properties of ultrathin two-dimensional (2D) layered
      nanomaterials are highly related to their thickness. Therefore, the rapid and
      accurate identification of single- and few- to multilayer nanosheets is essential
      to their fundamental study and practical applications. Here, a universal optical
      method has been developed for simple, rapid, and reliable identification of
      single- to quindecuple-layer (1L-15L) 2D nanosheets, including graphene, MoS2,
      WSe2, and TaS2, on Si substrates coated with 90 or 300 nm SiO2. The optical
      contrast differences between the substrates and 2D nanosheets with different
      layer numbers were collected and tabulated, serving as a standard reference, from
      which the layer number of a given nanosheet can be readily and reliably
      determined without using complex calculation or expensive instrument. Our general
      optical identification method will facilitate the thickness-dependent study of
      various 2D nanomaterials and expedite their research toward practical
      applications. 

PMID- 24131443
TI  - Detection of intestinal protozoa in paediatric patients with gastrointestinal
      symptoms by multiplex real-time PCR.
AB  - The performance of a multiplex real-time PCR for the detection of Blastocystis,
      Dientamoeba fragilis, Giardia lamblia, Cryptosporidium species and Entamoeba
      species in faecal samples was evaluated in an observational prospective study.
      Paediatric patients (0-18 years) presenting with gastrointestinal symptoms and
      suspected of having enteroparasitic disease were included. A questionnaire on
      gastrointestinal symptoms and the chosen treatment was completed at the start of
      the study and after 6 weeks. Of 163 paediatric patients (mean age, 7.8 years),
      114 (70%) had a PCR-positive faecal sample. D. fragilis was detected most
      frequently, in 101 patients, followed by Blastocystis in 49. In faecal samples of
      47 patients, more than one protozoan was detected, mainly the combination of D.
      fragilis and Blastocystis. Reported gastrointestinal symptoms were abdominal pain
      (78%), nausea (30%), and altered bowel habits (28%). Eighty-nine of the PCR
      positive patients were treated with antibiotics. A significant reduction in
      abdominal pain was observed both in treated and in untreated patients. This study
      demonstrated that multiplex real-time PCR detects a high percentage of intestinal
      protozoa in paediatric patients with gastrointestinal symptoms. However,
      interpretation and determination of the clinical relevance of a positive PCR
      result in this population are still difficult.

PMID- 24131444
TI  - Enantioselective total synthesis of (-)-limaspermidine and formal synthesis of (
      )-1-acetylaspidoalbidine.
AB  - Evolution of the synthetic strategy that culminated in the first asymmetric total
      synthesis of the Aspidosperma alkaloid limaspermidine is described. The
      successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and
      with the isolation of only six intermediates using a Pd-catalyzed
      enantioselective decarboxylative allylation we have recently developed. This
      first enantioselective synthesis of (-)-limaspermidine establishes unambiguously
      its absolute configuration and allows the first asymmetric formal total synthesis
      of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine. 

PMID- 24131445
TI  - The validity of the body adiposity index in predicting percentage body fat and
      cardiovascular risk factors among Chinese.
AB  - OBJECTIVE: Recent research has suggested that body adiposity index (BAI)
      correlates more closely with percentage body fat (PBF) than body mass index
      (BMI). Here, we aimed to evaluate BAI's predictive power for PBF and for obesity
      associated risk factors in the Chinese population. SUBJECTS: A total of 1707
      women and 680 men aged 51-77 years were analysed in this community-based cross
      sectional study. MEASUREMENTS: Body weight, height, waist circumference (WC) and
      hip circumference (HC) were measured, and BMI and BAI were calculated. Percentage
      body fat was determined by dual-energy X-ray absorptiometry (DXA). Blood
      pressure, fasting lipid profiles, glucose and Carotid ultrasound examination
      determined intima-media thickness (IMT) at the common carotid arteries (CCA) were
      also measured. RESULTS: The Pearson correlation analysis indicated a stronger
      correlation between BAI and PBF when women and men were pooled together, but this
      effect disappeared in sex-stratified analysis. Bland-Altman plots suggested that
      BAI underestimated 5.8% of PBF in women and slightly overestimated 0.28% of PBF
      in men, but the magnitudes of these biases showed a fat mass-dependent manner.
      Both the logistic regression and the receiver operating characteristic curve
      (ROC) analysis indicated that BAI has an inferior predictive power for the
      presence of hypertension, dyslipidaemia, metabolic syndrome and CCA-intima-media
      thickening, compared with BMI and WC. CONCLUSION: We concluded that BAI was
      neither a better predictor for PBF nor for cardiovascular risks in Chinese
      population compared with BMI and WC.

PMID- 24131446
TI  - Giant left atrium.

PMID- 24131447
TI  - Efficacy of narrowband ultraviolet phototherapy on renal pruritus.
AB  - AIMS AND OBJECTIVES: To test the efficacy of narrowband ultraviolet B
      phototherapy in reducing renal pruritus. BACKGROUND: Renal pruritus is a
      disabling symptom affecting approximately 50% of patients undergoing maintenance
      haemodialysis. Managing refractory pruritus can be a great challenge for
      healthcare providers and patients as well. For patients who do not respond to
      conventional treatments, ultraviolet B phototherapy is considered the treatment
      of choice. Few investigators, however, have studied the efficacy of narrowband
      ultraviolet B phototherapy in this condition. DESIGN: The study was based on a
      quasi-experimental design with repeated measures. METHODS: A convenience sample
      of 42 haemodialysis patients with pruritus was recruited from haemodialysis units
      of a general hospital in Taipei, Taiwan. Two groups were created according to the
      dates of haemodialysis. The intervention participants received narrowband
      ultraviolet B phototherapy three times a week for two weeks. The control
      participants were maintained on their prior pruritus treatment. The pruritus
      intensity was measured with a numerical rating scale at baseline and on
      alternating days for seven times. Data were collected during the year 2008.
      RESULTS: The generalised estimating equation showed statistically significant
      group-by-time interactions in pruritus intensity. Using the control group as the
      reference group and baseline as the reference time, the intervention group had
      significantly lower pruritus intensity than the control group: 3.14 (p < 0.001)
      at time seven, 1.71 (p < 0.001) at time six and 1.24 at time five (p < 0.001).
      The group-by-time interactions were statistically significant after four sessions
      of narrowband-UVB irradiation. CONCLUSION: The study findings support the
      efficacy of narrowband ultraviolet B phototherapy in alleviating renal pruritus.
      RELEVANCE TO CLINICAL PRACTICE: Clinicians may consider prescribing phototherapy
      for haemodialysis patients who have intractable renal pruritus and do not respond
      to conventional treatments.

PMID- 24131448
TI  - Oxidative stress in Alzheimer's disease: are we connecting the dots?
AB  - Redox impairment is a prominent feature of Alzheimer's disease (AD). It has led
      to the "oxidative stress hypothesis", which proposes antioxidants as beneficial
      therapeutic tools in AD treatment. To date, a wide variety of antioxidants have
      been examined as neuroprotectants. However, success has been elusive in clinical
      trials. Several factors have contributed to this failure, including the
      complexity of the redox system in vivo. Potentially critical aspects include the
      fine-tuned equilibrium between antioxidant defenses and free radical production,
      the lack of specific antioxidant target(s), and the inherent difficulty in
      delivering antioxidants where they are needed. Herein, we highlight significant
      progress in the field. Future directions of antioxidant research are also
      presented. 

PMID- 24131449
TI  - Attitudes of health professionals towards electronic health records in primary
      health care settings: a questionnaire survey.
AB  - PURPOSE: This study aimed to assess the attitudes of health professionals towards
      electronic health records (EHRs) in primary health care settings in Turkey.
      METHODS: A survey was administered to 754 health professionals working in Family
      Health Centres (FHCs) in seven districts in Istanbul, Turkey. The survey was
      developed based on extensive literature review, and consisted of 33 statements
      rated on a five-point Likert-scale. RESULTS: A total of 325 completed
      questionnaires were received, representing a 43% response rate, with 97% of
      respondents being satisfied with the EHR system in the FHCs. There were
      significant differences between health professional groups (physicians and
      nurses/midwives) in their perceptions of EHRs decreasing paper-based records,
      data security in EHRs, and costs of EHRs (p < 0.05). Narrative responses
      indicated ongoing needs in software development, further support of nursing
      documentation and training. CONCLUSIONS: Overall positive attitudes towards EHRs
      among primary care health professionals in Turkey suggest strong acceptance and
      use. Recommendations based on the findings include EHR technology refinements,
      improved clinical documentation using standardized terminologies, and health
      professional-informed EHR training.

PMID- 24131450
TI  - The role of self-aspects in emotions elicited by threats to physical health.
AB  - In two studies, we examined the relationship between self-aspects and socially
      engaging and socially disengaging emotions elicited by imagined and real physical
      health problems. In Study 1, participants imagined themselves experiencing a
      health problem described in a hypothetical scenario and rated the extent to which
      they would experience a list of emotions. The experience of socially engaging
      emotions such as shame and embarrassment was predicted by the endorsement of
      collective self. In Study 2, participants recalled a past health problem and
      emotions they experienced during its course. Again, collective self predicted the
      extent to which people mentioned socially engaging emotions in their free recall
      of emotions. Independent self was not related to the imagined experience of
      socially disengaging emotions in Study 1 or the recollection of such emotions in
      Study 2. 

PMID- 24131451
TI  - Novel use of cavity ring-down spectroscopy to investigate aquatic carbon cycling
      from microbial to ecosystem scales.
AB  - Development of cavity ring-down spectroscopy (CRDS) has enabled real-time
      monitoring of carbon stable isotope ratios of carbon dioxide and methane in air.
      Here we demonstrate that CRDS can be adapted to assess aquatic carbon cycling
      processes from microbial to ecosystem scales. We first measured in situ
      isotopologue concentrations of dissolved CO2 ((12)CO2 and (13)CO2) and CH4
      ((12)CH4 and (13)CH4) with CRDS via a closed loop gas equilibration device during
      a survey along an estuary and during a 40 h time series in a mangrove creek
      (ecosystem scale). A similar system was also connected to an in situ benthic
      chamber in a seagrass bed (community scale). Finally, a pulse-chase isotope
      enrichment experiment was conducted by measuring real-time release of (13)CO2
      after addition of (13)C enriched phytoplankton to exposed intertidal sediments
      (microbial scale). Miller-Tans plots revealed complex transformation pathways and
      distinct isotopic source values of CO2 and CH4. Calculations of delta(13)C-DIC
      based on CRDS measured delta(13)C-CO2 and published fractionation factors were in
      excellent agreement with measured delta(13)C-DIC using isotope ratio mass
      spectroscopy (IRMS). The portable CRDS instrumentation used here can obtain real
      time, high precision, continuous greenhouse gas data in lakes, rivers, estuaries
      and marine waters with less effort than conventional laboratory-based techniques.

PMID- 24131452
TI  - Enhanced adsorption of Ca-ATPase containing vesicles on a negatively charged
      solid-supported-membrane for the investigation of membrane transporters.
AB  - A convenient model system for a biological membrane is a solid-supported membrane
      (SSM), which consists of a gold-supported alkanethiol|phospholipid bilayer. In
      combination with a concentration jump method, SSMs have been used for the
      investigation of several membrane transporters. Vesicles incorporating
      sarcoplasmic reticulum Ca-ATPase (SERCA) were adsorbed on a negatively charged
      SSM (octadecanethiol|phosphatidylserine bilayer). The current signal generated by
      the adsorbed vesicles following an ATP concentration jump was compared to that
      produced by SERCA-containing vesicles adsorbed on a conventional SSM
      (octadecanethiol|phosphatidylcholine bilayer). A significantly higher current
      amplitude was recorded on the serine-based SSM. The adsorption of SERCA
      incorporating vesicles on the SSM was then characterized by surface plasmon
      resonance (SPR). The SPR measurements clearly indicate that in the presence of
      Ca(2+) and Mg(2+), the amount of adsorbed vesicles on the serine-based SSM is
      about twice that obtained using the conventional SSM, thereby demonstrating that
      the higher current amplitude recorded on the negatively charged SSM is correlated
      with a greater quantity of adsorbed vesicles. The enhanced adsorption of membrane
      vesicles on the PS-based SSM may be useful to study membrane preparations with a
      low concentration of transport protein generating small current signals, as in
      the case of various recombinantly expressed proteins. 

PMID- 24131453
TI  - Outcomes of radical cystectomy with extended lymphadenectomy alone in patients
      with lymph node-positive bladder cancer who are unfit for or who decline adjuvant
      chemotherapy.
AB  - OBJECTIVE: To analyse the long-term outcomes of patients with lymph node (LN)
      positive bladder cancer, who did not receive any adjuvant therapy after radical
      cystectomy (RC) and extended pelvic lymph node dissection (ePLND). PATIENTS AND
      METHODS: We conducted a retrospective, combined cohort analysis based on two
      prospectively maintained cystectomy databases from the University of Southern
      California and the University of Bern. Eligible patients underwent RC with ePLND
      for cN0M0 disease but were found to have LN-positive disease. No patient had
      neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots
      were used to estimate recurrence-free survival (RFS) and overall survival (OS).
      Subgroup comparisons were performed using log-rank tests, and multivariable
      analysis was based on Cox proportional hazard models. RESULTS: Of 521 patients
      with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the
      pathological stage distribution was similar, the 251 patients who did not receive
      adjuvant therapy were older and had both fewer total and positive LNs than those
      who underwent adjuvant therapy. The median RFS for patients treated with RC alone
      was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and
      10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total
      number of LNs and the number of positive LNs detected were independent predictors
      of RFS and OS. CONCLUSIONS: In this study, 25% of patients with documented LN
      metastases who did not receive adjuvant therapy were cured with RC and ePLND;
      however, a few relapses may occur later than 3 years. Predictors of survival were
      pathological T stage, the number of total LNs and the number of positive LNs
      identified.

PMID- 24131458
TI  - Antidepressant and QT interval prolongation, how should we look at this issue?
      Focus on citalopram.
AB  - INTRODUCTION: Evidence increasingly points to the potential development of
      harmful cardiac side effects concomitant with the use of a number of psychotropic
      drugs, primarily traditional antipsychotics and tricyclic antidepressants. AREAS
      COVERED: The US Food and Drug Administration announced safety warnings associated
      with the use of citalopram with QT interval prolongation in 2011 and 2012. This
      paper explores the clinical background of QT interval prolongation, clinical data
      related to antidepressants and QT interval prolongation, the clinical
      implications of safety issues associated with the use of antidepressants and
      future research directions. EXPERT OPINION: Currently available evidence proposes
      that citalopram may not be definitely associated with the increase of cardiac
      mortality, although it should be related with increase of QT prolongation. A firm
      consensus regarding the cardiac safety issues associated with antidepressants has
      to be established in near future. Hence, the choice of an individual
      antidepressant regarding cardiac safety issues should be based on multiple
      factors; clinicians may need to select the best available antidepressant for each
      individual based on that patient's vulnerability, the proven efficacy and safety
      of each agent and a reasonable benefit:risk ratio, based on currently available
      findings.

PMID- 24131459
TI  - [Hip fractures].
AB  - Hip fractures are ranked among the frequent injuries. These fractures have been
      often coupled with high energy trauma in children and in patients with normal
      bone structure, low energy trauma and osteoporotic fracture (fragility fracture)
      is typical in elder patients. Hip fractures are divided into five groups: femoral
      head fracture, femoral neck fracture, pertrochanteric, intertrochateric and
      subtrochanteric fracture. Surgical treatment is indicated in all patients unless
      contraindications are present. Long bed rest has been accompanied by a high risk
      of development of thromboembolic disease, pneumonia and bed sore. Healing in the
      wrong position and nonunions are often the result of conservative treatment.
      Screw osteosynthesis is performed in isolated femoral head factures. Three
      cannulated screws or a DHS plate (dynamic hip screw) are used in fractures of the
      femoral neck with normal femoral head perfusion, total hip replacement is
      recommended in elder patients and in case of loss of blood supply of the femoral
      head. Pertrochanteric and intertrochanteric fractures can be stabilized by the
      femoral nails (PFN, PFN A, PFH - proximal femoral nail), nails are suitable for
      minimally invasive insertion and provide higher stability in the shaft, or plates
      (DHS) designed for stable pertronchanteric and intertrochanteric fractures.
      Subtrochanteric fractures can be fixed also intramedullary (nails - PFN long, PFN
      A long) and extramedullary (plates - DCS dynamic condylar screw, proximal femoral
      LCP - locking compression plate). Open reduction with internal plate fixation is
      advantageous for pathological fractures, as biopsy sampling can be performed. Hip
      fracture rehabilitation is integral part of the treatment, including walking on
      crutches or with a walker with partial weight bearing for at least six weeks.

PMID- 24131460
TI  - [Dynamics of serum visfatin level after abdominal surgery: a new proinflammatory
      marker in the early diagnosis?].
AB  - BACKGROUND: Visfatin is a newly recognized adipocytokine produced mainly in
      visceral fat tissue. Beside its effect on insulin receptor, it serves as
      proinflammatory cytokine and its level can be changed during inflammatory
      processes. The aim of the study was to analyze dynamics of serum visfatine level
      in early period after abdominal surgery and compare it with other proinflammatory
      markers. METHODS AND RESULTS: In prospective cross-sectional study 20 patients
      after elective laparotomic abdominal surgery (partial colectomy) were enrolled
      and dynamics of visfatin, leptin, resistin, adiponectin, TNF-alpha , IL-6 and CRP
      in period +12, +24, +48 and + 72 hours was monitored. Serum visfatin was elevated
      already in +24 hrs period after surgery comparing the culmination of serum level
      of TNF-alpha and IL-6 12-24 hrs later and CRP even 48-72 hrs later. CONCLUSIONS:
      Serum visfatin was elevated very early after abdominal surgery and thus its
      dynamic may be an early predictor of inflammatory processes namely in patients
      with visceral obesity.

PMID- 24131461
TI  - [Comparing quality of life in dialysis patients and patients after kidney
      transplantation: a questionnaire survey].
AB  - BACKGROUND: The aim of the study was to determine and compare quality of life in
      patients with chronic kidney failure treated with dialysis and those after kidney
      transplantation. METHODS AND RESULTS: The group comprised 199 patients with
      chronic kidney failure (99 dialysis patients and 100 patients after kidney
      transplantation). Data were collected using the WHOQOL-BREF questionnaire for
      assessing quality of life. Patients after kidney transplantation had
      statistically significantly higher quality of life scores in all domains than
      dialysis patients (p < 0.001). When compared with the general population,
      patients after transplantation showed lower quality of life only in the physical
      health domain (p < 0.001) and separate item measuring satisfaction with health (p
      < 0.01). Dialysis patients had lower quality of life than the normal population
      in all domains and separate items, the only exception being the environment
      domain(p < 0.001). Dialysis patients quality of life significantly decreased in
      all domains with time from the initiation of dialysis therapy (p < 0.05).
      CONCLUSIONS: Information about QoL of patients with renal failure treated by
      different approaches may help both doctors and patients and their families when
      making decisions about therapy selection.

PMID- 24131462
TI  - [Smoking is a political disease].
AB  - Current research concerning tobacco health impact revealed clear conclusions:
      both active and passive smoking cause diseases and premature death. No more
      research in this field is needed: we just need to eliminate tobacco from the
      society. Research outputs which have not been used represent wasting of
      resources. The evidence we have should be used to add more countries on the list
      of those with detailed End Game plans, like Finland, New Zealand or Australia. It
      means to decrease tobacco availability, protect population from tobacco smoke
      exposition, and support broadly available treatment of tobacco dependence.

PMID- 24131463
TI  - [Teaching at the Czech Faculty of Medicine has started 130 years ago].
AB  - Act on the division of Charles-Ferdinand University in Prague into the Czech and
      German universities was signed by the emperor on 28 February 1882. Czech Faculty
      of Medicine was able to start education only in the school year 1882/83, one year
      after the Faculty of Law and Faculty of Arts. It was necessary to establish all
      institutes of theoretical medicine and some clinical departments, because German
      professors transferred their clinics to the German University, which the Act
      allowed. Celebration of the beginning of the teaching at the Czech Faculty of
      Medicine was imposing and it was described in the Journal of Czech Physicians and
      in the daily papers.

PMID- 24131464
TI  - New continuous fluorometric assay for bacterial transglycosylase using Forster
      resonance energy transfer.
AB  - The emergence of antibiotic resistance has prompted scientists to search for new
      antibiotics. Transglycosylase (TGase) is an attractive target for new antibiotic
      discovery due to its location on the outer membrane of bacteria and its essential
      role in peptidoglycan synthesis. Though there have been a few molecules
      identified as TGase inhibitors in the past thirty years, none of them have been
      developed into antibiotics for humans. The slow pace of development is perhaps
      due to the lack of continuous, quantitative, and high-throughput assay available
      for the enzyme. Herein, we report a new continuous fluorescent assay based on
      Forster resonance energy transfer, using lipid II analogues with a dimethylamino
      azobenzenesulfonyl quencher in the lipid chain and a coumarin fluorophore in the
      peptide chain. During the process of transglycosylation, the quencher-appended
      polyprenol is released and the fluorescence of coumarin can be detected. Using
      this system, the substrate specificity and affinity of lipid II analogues bearing
      various numbers and configurations of isoprene units were investigated. Moreover,
      the inhibition constants of moenomycin and two previously identified small
      molecules were also determined. In addition, a high-throughput screening using
      the new assay was conducted to identify potent TGase inhibitors from a 120,000
      compound library. This new continuous fluorescent assay not only provides an
      efficient and convenient way to study TGase activities, but also enables the high
      throughput screening of potential TGase inhibitors for antibiotic discovery. 

PMID- 24131465
TI  - Involvement of proteinase activated receptor-2 in the vascular response to
      sphingosine 1-phosphate.
AB  - S1P (sphingosine 1-phosphate) represents one of the key latest additions to the
      list of vasoactive substances that modulate vascular tone. PAR-2 (proteinase
      activated receptor-2) has been shown to be involved in cardiovascular function.
      In the present study, we investigated the involvement of PAR-2 in S1P-induced
      effect on vascular tone. The present study has been performed by using isolated
      mouse aortas. Both S1P and PAR-2 agonists induced endothelium-dependent
      vasorelaxation. L-NAME (N(G)-nitro-L-arginine methyl ester) and wortmannin
      abrogated the S1P-induced vasorelaxatioin, while significantly inhibiting the PAR
      2-mediated effect. Either ENMD1068, a PAR-2 antagonist, or gabexate, a serine
      protease inhibitor, significantly inhibited S1P-induced vasorelaxation. Aortic
      tissues harvested from mice overexpressing PAR-2 displayed a significant increase
      in vascular response to S1P as opposed to PAR-2-null mice. Immunoprecipitation
      and immunofluorescence studies demonstrated that S1P(1) interacted with PAR-2 and
      co-localized with PAR-2 on the vascular endothelial surface. Furthermore, S1P
      administration to vascular tissues triggered PAR-2 mobilization from the plasma
      membrane to the perinuclear area; S1P-induced translocation of PAR-2 was
      abrogated when aortic rings were pre-treated with ENMD1068 or when caveolae
      dysfunction occurred. Similarly, experiments performed in cultured endothelial
      cells (human umbilical vein endothelial cells) showed a co-localization of S1P(1)
      and PAR2, as well as the ability of S1P to induce PAR-2 trafficking. Our results
      suggest that S1P induces endothelium-dependent vasorelaxation mainly through
      S1P(1) and involves PAR-2 transactivation.

PMID- 24131466
TI  - Evaluation of the chronic obstructive pulmonary disease assessment test in
      Japanese outpatients.
AB  - OBJECTIVE: The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT)
      is a quality-of-life (QOL) questionnaire that proved to correlate with St.
      George's Respiratory Questionnaire. Correlations between CAT scores and other
      COPD parameters have not been thoroughly evaluated in Japanese outpatients.
      METHODS: Cross-sectional study of 85 outpatients with COPD at a Japanese
      community-based hospital. PATIENTS: We observed 70 men and 15 women, whose
      average age was 72.0 +/- 9.0 years. Mean forced expiratory volume in 1 s (FEV1)
      (% predicted) was 45.8 +/- 14.7%. Mean CAT score was 10.1 +/- 7.9 (range: 0-31).
      We calculated Spearman's rank correlation coefficient for CAT score and the
      following variables: r=0.81 for 'the Body Mass Index, Airflow Obstruction,
      Dyspnea and Exercise Capacity Index'; r=-0.05 for body mass index; r=-0.56 for
      FEV1 (% predicted); r=0.88 for Modified Medical Research Council Dyspnea Scale;
      r=-0.71 for 6-min walk distance; r=0.68 for 'the Age, Dyspnoea,and Airflow
      Obstruction Index'; and r=-0.40 for oxygen saturation in artery. Each COPD
      parameter, except for body mass index, had a significant (P<0.001) correlation
      with the CAT score. CONCLUSIONS: The CAT score, which is obtainable by a simple
      questionnaire originally designed for QOL assessment, had strong correlations
      with airflow obstruction, dyspnea, exercise tolerance, prognostic index and
      oxygenation in Japanese outpatients.

PMID- 24131467
TI  - A retrospective chart review of the use of rituximab for the treatment of
      rheumatoid arthritis in Australian rheumatology practice.
AB  - AIM: Rituximab is one of nine biologic agents approved for the treatment of
      rheumatoid arthritis (RA) in Australia. The primary study objective was to
      analyze the factors that lead to the therapeutic decision to use rituximab in RA.
      METHOD: A cross-sectional, retrospective chart review was conducted to identify
      patients who were treated with rituximab and to evaluate their response to
      treatment. RESULTS: Factors influencing the prescription of rituximab were
      identified. The most commonly reported reason for prescribing rituximab was the
      presence of comorbidities and the presence of seropositive disease. Median
      rituximab treatment duration was 32.5 months and mean number of treatment cycles
      was 4.1. Disease activity scores showed significant improvement from baseline to
      most recent visit. Rituximab treatment was well-tolerated in this group of RA
      patients. CONCLUSIONS: Rituximab was effective in a refractory group of RA
      patients and appears to be safe in a population with a high prevalence of
      comorbidities, including malignancy and recurrent infections/bronchiectasis. This
      study may assist rheumatologists in selecting appropriately targeted therapy in
      RA.

PMID- 24131468
TI  - I(2)-catalyzed direct alpha-hydroxylation of beta-dicarbonyl compounds with
      atmospheric oxygen under photoirradiation.
AB  - An I2-catalyzed hydroxylation of beta-dicarbonyl moieties using air as the
      oxidant under photoirradiation has been developed for the easy preparation of
      alpha-hydroxy-beta-dicarbonyl compounds. The transformation was completed with
      only 1 mol % of I2. With alpha-unsubstituted malonates, the hydroxylated
      dimerization product was afforded as the predominant product along with a minor
      product, alpha,alpha-dihydroxyl malonate. 

PMID- 24131470
TI  - Regulating bioactivity of Cu2+ bis-1,10-phenanthroline artificial
      metallonucleases with sterically functionalized pendant carboxylates.
AB  - The synthetic chemical nuclease, [Cu(1,10-phenanthroline)2](2+), has stimulated
      research within metallonuclease development and in the area of cytotoxic
      metallodrug design. Our analysis reveals, however, that this agent is
      "promiscuous" as it binds both dsDNA and protein biomolecules, without
      specificity, and induces general toxicity to a diversity of cell lineages. Here,
      we describe the synthesis and characterization of small-molecule metallonucleases
      containing the redox-active cation, [Cu(RCOO)(1,10-phen)2](+), where 1,10-phen =
      1,10-phenanthroline and R = -H, -CH3, -C2H5, -CH(CH3)2, and -C(CH3)3. The
      presence of coordinated carboxylate groups in the complex cation functions to
      enhance dsDNA recognition, reduce serum albumin binding, and offer control of
      toxicity toward human cancer cells, Gram positive and negative bacteria, and
      fungal pathogens. The induction of genomic dsDNA breaks (DSBs) were identified in
      ovarian adenocarcinoma cells using immunodetection of gamma-H2AX. Formate,
      acetate, and pivalate functionalized complexes induced DSBs in a higher
      percentage of cells compared with [Cu(1,10-phen)2](2+), which supports the
      importance of inner-sphere modification toward enhancing targeted biological
      application. 

PMID- 24131471
TI  - Peptide tag/probe pairs based on the coordination chemistry for protein labeling.
AB  - Protein-labeling methods serve as essential tools for analyzing functions of
      proteins of interest under complicated biological conditions such as in live
      cells. These labeling methods are useful not only to fluorescently visualize
      proteins of interest in biological systems but also to conduct protein and cell
      analyses by harnessing the unique functions of molecular probes. Among the
      various labeling methods available, an appropriate binding pair consisting of a
      short peptide and a de novo designed small molecular probe has attracted
      attention because of its wide utility and versatility. Interestingly, most
      peptide tag/probe pairs exploit metal-ligand coordination interactions as the
      main binding force responsible for their association. Herein, we provide an
      overview of the recent progress of these coordination-chemistry-based protein
      labeling methods and their applications for fluorescence imaging and functional
      analysis of cellular proteins, while highlighting our originally developed
      labeling methods. These successful examples clearly exemplify the utility and
      versatility of metal coordination chemistry in protein functional analysis. 

PMID- 24131469
TI  - Systematic interrogation of the Conus marmoreus venom duct transcriptome with
      ConoSorter reveals 158 novel conotoxins and 13 new gene superfamilies.
AB  - BACKGROUND: Conopeptides, often generically referred to as conotoxins, are small
      neurotoxins found in the venom of predatory marine cone snails. These molecules
      are highly stable and are able to efficiently and selectively interact with a
      wide variety of heterologous receptors and channels, making them valuable
      pharmacological probes and potential drug leads. Recent advances in next
      generation RNA sequencing and high-throughput proteomics have led to the
      generation of large data sets that require purpose-built and dedicated
      bioinformatics tools for efficient data mining. RESULTS: Here we describe
      ConoSorter, an algorithm that categorizes cDNA or protein sequences into
      conopeptide superfamilies and classes based on their signal, pro- and mature
      region sequence composition. ConoSorter also catalogues key sequence
      characteristics (including relative sequence frequency, length, number of
      cysteines, N-terminal hydrophobicity, sequence similarity score) and
      automatically searches the ConoServer database for known precursor sequences,
      facilitating identification of known and novel conopeptides. When applied to
      ConoServer and UniProtKB/Swiss-Prot databases, ConoSorter is able to recognize
      100% of known conotoxin superfamilies and classes with a minimum species
      specificity of 99%. As a proof of concept, we performed a reanalysis of Conus
      marmoreus venom duct transcriptome and (i) correctly classified all sequences
      previously annotated, (ii) identified 158 novel precursor conopeptide
      transcripts, 106 of which were confirmed by protein mass spectrometry, and (iii)
      identified another 13 novel conotoxin gene superfamilies. CONCLUSIONS: Taken
      together, these findings indicate that ConoSorter is not only capable of robust
      classification of known conopeptides from large RNA data sets, but can also
      facilitate de novo identification of conopeptides which may have pharmaceutical
      importance.

PMID- 24131473
TI  - Automated synthesis of photovoltaic-quality colloidal quantum dots using separate
      nucleation and growth stages.
AB  - As colloidal quantum dot (CQD) optoelectronic devices continue to improve,
      interest grows in the scaled-up and automated synthesis of high-quality
      materials. Unfortunately, all reports of record-performance CQD photovoltaics
      have been based on small-scale batch syntheses. Here we report a strategy for
      flow reactor synthesis of PbS CQDs and prove that it leads to solar cells having
      performance similar to that of comparable batch-synthesized nanoparticles.
      Specifically, we find that, only when using a dual-temperature-stage flow reactor
      synthesis reported herein, are the CQDs of sufficient quality to achieve high
      performance. We use a kinetic model to explain and optimize the nucleation and
      growth processes in the reactor. Compared to conventional single-stage flow
      synthesized CQDs, we achieve superior quality nanocrystals via the optimized dual
      stage reactor, with high photoluminescence quantum yield (50%) and narrow full
      width-half-maximum. The dual-stage flow reactor approach, with its versatility
      and rapid screening of multiple parameters, combined with its efficient materials
      utilization, offers an attractive path to automated synthesis of CQDs for
      photovoltaics and, more broadly, active optoelectronics. 

PMID- 24131472
TI  - CMTM3 inhibits cell migration and invasion and correlates with favorable
      prognosis in gastric cancer.
AB  - The CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) gene is a novel
      tumor suppressor with frequent epigenetic inactivation. In this study, we showed
      the role played by CMTM3 in gastric cancer cells as a tumor suppressor gene, and
      examined the correlation between CMTM3 expression and clinicopathological
      parameters using immunohistochemistry in gastric cancer patients with different
      pathological stages (n = 350). We found that CMTM3 expression was reduced or
      silenced by epigenetic regulation in gastric cell lines, and dramatically
      downregulated in primary gastric cancer tissues. Restoration of CMTM3
      significantly affected migration and invasion of AGS and SGC-7901 cells (P <
      0.001). In vivo experiments showed that peritoneal disseminated metastases were
      significantly suppressed by CMTM3 (P < 0.001). We further showed that the
      expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3
      was restored. In addition, by immunohistochemical staining, we found that the
      expression of CMTM3 was remarkably weaker in gastric cancer tissues than in
      normal mucosae (P = 0.008), and was significantly correlated with gender (P =
      0.033), tumor depth (P = 0.049), stage (P = 0.021), and histological grade (P =
      0.022). More importantly, CMTM3 expression was associated with prognosis in
      gastric cancer patients (P = 0.041), and was a significant independent prognostic
      indicator (hazard ratio = 0.704, 95% confidence interval, 0.498-0.994; P =
      0.046). Our findings indicate that CMTM3 regulates migration and invasion of
      gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of
      gastric cancer in the clinic.

PMID- 24131474
TI  - Left ventricular pseudoaneurysm after perventricular ventricular septal defect
      device closure.
AB  - Perventricular ventricular septal defect (VSD) closure has been adopted as a
      therapeutic option for selected patients with muscular VSDs. This technique may
      combine some of the advantages of surgical and interventional techniques.
      Complication rates have been low: only one case of procedure-related left
      ventricular (LV) pseudoaneurysm has been documented. We report the surgical
      repair for a LV pseudoaneurysm after perventricular VSD device closure.

PMID- 24131475
TI  - N-acetylgalactosamine exposure of serum IgA1 was associated with
      glomerulosclerosis and tubular atrophy/interstitial fibrosis of IgA nephropathy
      patients.
AB  - AIM: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis
      with various histological and clinical phenotypes. N-acetylgalactosamine (GalNAc)
      exposure plays a pivotal role in the pathogenesis of IgAN. The aim of the current
      study is to investigate whether GalNAc exposure of serum IgA1 was associated with
      clinical and pathological manifestation of IgAN. METHODS: Sera from 199 patients
      with biopsy proved IgAN were collected. Clinical and pathological manifestations
      were collected. Biotinylated Helix aspersa were used in ELISA to examine GalNAc
      exposure on IgA1 molecules. Patients were divided into two groups according to
      the GalNAc exposure rate less or more than 0.4. RESULTS: Age, gender, and serum
      creatinine were comparable between the two groups. Univariate analysis showed
      that significantly higher urinary protein excretion rate but less severe
      glomerular sclerosis and tubularinterstitial fibrosis were observed in the lower
      GalNAc exposure group. Multivariate regression analysis demonstrated that
      adjusted by age and gender, the GalNAc exposure rate more than 0.4 was a risk
      factor of glomerular sclerosis and tubularinterstitial fibrosis, OR*(95% CI) were
      2.76 (1.19-6.37) and 2.49 (1.18-5.25), respectively. CONCLUSION: Immunoglobulin A
      nephropathy patients with lower proteinuria had higher GalNAc exposure rates. The
      GalNAc exposure rate more than 0.4 was a risk factor of severe chronic renal
      tissue change.

PMID- 24131476
TI  - Application of variant-calling algorithms for Mendelian disorders: lessons from
      whole-exome sequencing in Charcot-Marie-Tooth disease.

PMID- 24131477
TI  - The contribution of the HIV specialist nurse to HIV care: a scoping review.
AB  - AIMS AND OBJECTIVES: To systematically identify and critically examine the
      evidence of the contribution of the HIV nurse specialist to provision of HIV care
      in the UK and other developed countries. BACKGROUND: The HIV clinical nurse
      specialist role has evolved over the past two decades in response to changes in
      two areas of HIV care: first, changes in the treatment and care of those with HIV
      and second, changes and development in advanced nursing practice. The challenges
      facing HIV care require the development of innovative services including a
      greater contribution of HIV specialist nurses. A review of current evidence is
      required to inform developments. DESIGN: A review. METHODS: A broad search
      strategy was used to search electronic databases. Grey literature was accessed
      through a variety of approaches. Preference was given to UK literature with
      inclusion of international publications from other developed countries where
      relevant. RESULTS: Fourteen articles were included. Four themes were identified:
      the diversity of the clinical role; a knowledge and skills framework for HIV
      nursing practice; the education and training role of the HIV nurse specialist;
      and the effectiveness of the HIV nurse specialist. The findings mainly focus on
      the clinical aspects of the role with little evidence concerning other aspects.
      There is limited evidence to indicate clinical effectiveness. CONCLUSIONS: HIV
      care is facing substantial challenges, and there is a clear need to develop
      effective and efficient services, including expanding the contribution of HIV
      nurse specialists. Such developments need to occur within a framework that
      optimises nursing contribution and measures their impact on HIV care. This review
      provides a baseline to inform such developments. RELEVANCE TO CLINICAL PRACTICE:
      This review of the literature details current understanding of the role of HIV
      specialist nurses and the contribution that they make to HIV care.

PMID- 24131478
TI  - Changes in bacterial metabolism as a response to dissolved organic matter
      modification during protozoan grazing in coastal Cantabrian and Mediterranean
      waters.
AB  - We explored how marine dissolved organic matter (DOM) altered by bacterial growth
      and protozoan grazing modify the metabolism of Southeastern Cantabrian Sea (CS)
      and NW Mediterranean Sea (MS) coastal bacterial communities. Major metabolic
      features were measured in treatments with half of the natural water replaced by
      water with different DOM quality, characterized by fluorescent DOM analysis and
      collected from key times of the predator-prey curve. In both ecosystems,
      protozoan-altered DOM led to similar increases in bacterial carbon demand (238%
      and 213%) and decreases in bacterial growth efficiency (BGE: 56% for the CS and
      46% for the MS). These low BGEs were caused by similar bacterial production but
      much higher bacterial respiration rates, which in turn were positively related to
      aminopeptidase activity. However, in the CS bacterial community dominated by
      Bacteroidetes (41%), the enhanced hydrolytic activity was produced at a lower
      metabolic cost than in the MS, dominated by SAR11 (47%), which suggests a better
      adaptation of Bacteroidetes to the DOM altered during protozoan grazing. These
      results highlight protozoan grazing as a relevant factor influencing BGE in
      coastal ecosystems, and relate bacterial community composition to the major
      metabolic processes that result after a change in the quality of marine DOM. 

PMID- 24131479
TI  - Validation of the bladder control self-assessment questionnaire (B-SAQ) in men.
AB  - OBJECTIVE: To validate the Bladder Control Self-Assessment Questionnaire (B-SAQ),
      a short screener to assess lower urinary tract symptoms (LUTS) and overactive
      bladder (OAB) in men. PATIENTS AND METHODS: This was a prospective, single-centre
      study including 211 patients in a urology outpatient setting. All patients
      completed the B-SAQ and Kings Health Questionnaire (KHQ) before consultation, and
      the consulting urologist made an independent assessment of LUTS and the need for
      treatment. The psychometric properties of the B-SAQ were analysed. RESULTS: A
      total of 98% of respondents completed all items correctly in <5 min. The mean B
      SAQ scores were 12 and 3.3, respectively for cases (n = 101) and controls (n =
      108) (P < 0.001). Good correlation was evident between the B-SAQ and the KHQ. The
      agreement percentages between the individual B-SAQ items and the KHQ symptom
      severity scale were 86, 85, 84 and 79% for frequency, urgency, nocturia and
      urinary incontinence, respectively. Using a B-SAQ symptom score threshold of >=4
      alone had sensitivity, specificity and positive predictive values for detecting
      LUTS of 75, 86 and 84%, respectively, with an area under the curve of 0.88;
      however, in combination with a bother score threshold of >=1 these values changed
      to 92, 46 and 86%, respectively. CONCLUSIONS: The B-SAQ is an easy and quick
      valid case-finding tool for LUTS/OAB in men, but appears to be less specific in
      men than in women. The B-SAQ has the potential to raise awareness of LUTS.
      Further validation in a community setting is required.

PMID- 24131480
TI  - A day-by-day investigation of changes in criminal convictions before and after
      entering and leaving opioid maintenance treatment: a national cohort study.
AB  - BACKGROUND: Opioid maintenance treatment (OMT) is associated with reduced crime
      among heroin users, but little is known about how crime changes during different
      phases of treatment. The aim of this study was to investigate changes in criminal
      convictions on a day-to-day basis before and after entry or discharge from OMT.
      METHODS: National cohort study of all patients (n = 3221) in OMT in Norway 1997
      2003. Patients were followed over a 9-year period, before, during, and after
      treatment. Criminal convictions were studied on a day-to-day basis in relation to
      treatment status. A time-continuous estimate of the probability of convictions
      within the population for all days during observation was calculated. RESULTS:
      Changes in convictions were evident before changes of treatment status. During
      the 3 years prior to OMT, the convictions rate was approximately 0.4% per day.
      Prior to OMT, convictions decreased to about 0.2% per day on the day of treatment
      initiation. During the weeks before dropping out of treatment, convictions
      increased. The patterns during periods of transition were the same across gender,
      age and pre-treatment conviction-levels. CONCLUSIONS: Changes in convictions
      often occurred prior to changes in treatment status. Reductions in criminal
      convictions were found in the period before entry (or re-entry) to OMT, and
      increases in criminal activity were found in the months prior to treatment
      interruption.

PMID- 24131481
TI  - The effect of proatherogenic pathogens on adipose tissue transcriptome and fatty
      acid distribution in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Chronic infections have been demonstrated to maintain low-grade
      systemic inflammation and associate with atherosclerosis. We studied the
      inflammation- and lipid homeostasis-related effects of Aggregatibacter
      actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) infections on the
      epididymal and inguinal adipose tissue (AT) transcriptomes and fatty acid
      distribution in apolipoprotein (apo) E-deficient mice. Chow-fed apoE-deficient
      mice were exposed to 1) chronic intranasal infection with C. pneumoniae (Cpn
      group), 2) recurrent intravenous infection with A. actinomycetemcomitans (Aa
      group), 3) a combination of both types of infection (Cpn + Aa group), or 4)
      infection with the vehicle (control group). Epididymal and inguinal AT gene
      expression was analyzed using an Illumina Mouse WG-6 v2.0 platform and
      quantitative PCR (QPCR). Microarray data were analyzed using Gene Ontology
      enrichment analysis. AT fatty acid analysis was performed using gas-liquid
      chromatography. RESULTS: The transcriptomics data revealed significant enrichment
      in inflammation-associated biological pathways in both AT depots derived from the
      Aa and Cpn + Aa treated mice compared with the control group. The proportion of
      saturated fatty acids was higher in the inguinal AT in Aa (p = 0.027) and Cpn +
      Aa (p = 0.009) groups and in the epididymal AT in Aa group (p = 0.003). The
      proportion of polyunsaturated fatty acids was significantly lower among all Aa
      infected groups in both depots. Chronic Cpn infection displayed only minor
      effects on transcriptomics and fatty acids of the AT depots. CONCLUSIONS:
      Systemic infection with A. actinomycetemcomitans activates inflammation-related
      biological pathways and modulates cellular lipid homeostasis. The adverse changes
      in adipose tissues during chronic infection may promote atherosclerosis.

PMID- 24131482
TI  - Hypoglycemic effect of polysaccharides with different molecular weight of
      Pseudostellaria heterophylla.
AB  - BACKGROUND: The aims of this study were to evaluate the antidiabetic activity and
      to detect molecular size of Pseudostellaria heterophylla polysaccharide (PHP).
      Pseudostellaria heterophylla is a medicine extensively used in traditional
      Chinese medicine formulas to treat diabetes and its complications. METHODS:
      Molecular weight of PHP was determined by gel permeation chromatography combined
      with phenol-sulphuric acid method and the monosaccharides composition was
      determined by HPLC with a precolumn derivatization. Four polysaccharides with
      different molecular weight were compared for hypoglycemic active on two animal
      models both high does alloxan induced type1 diabetic mellitus (T1DM) and high
      fat/lower does streptozotocin induced type2 diabetic mellitus (T2DM). Blood
      sugar, glucose tolerance, and insulin tolerance were detected. Rat serum IL
      1beta, IL-2, IL-10, Leptin, TNF-alpha, Acrp30 and CRP were also analyzed by
      sandwich-ELISA approaches to preliminary probe the hypoglycemic mechanism of PHP.
      RESULTS: The hypoglycemic effects related to molecular size of polysaccharide
      were more effective against T2DM than T1DM. PHP comprise four monosaccharides of
      galacturonic acid, glucose, galactose and arabinos. T2DM rats daily receiving
      oral dose of polysaccharide(100 ~ 400 mg/kg) with 50 ~ 210 kDa molecular weight
      (PF40) could not only significantly lower blood sugar but also reduce total
      triglyceride level in serum. PF40 improves in insulin tolerance inhibited the
      expression of some biomarkers including inflammatory cytokine TNF-alpha and
      elevated anti-inflammatory cytokine IL-10, regulated adiponectin Acrp30 and
      leptin. CONCLUSIONS: PF40 prevent the cascade of inflammatory events in the
      treatment of T2DM to block overweight progresses to obesity.

PMID- 24131483
TI  - Thixotropic hydrogelators based on a cyclo(dipeptide) derivative.
AB  - Thixotropic hydrogelators have great potential in biomedical and biotechnological
      applications. In this study, we report new hydrogelators and their behavior
      during gel-sol-gel transitions. In particular, cyclo(L-O-hydroxyhexylaspartyl-L
      phenylalanyl), which was synthesized with 1,6-hexanediol, formed a
      thermally/isothermally reversible physical gel with several solvents, including
      pure water, saline, alcohols, as well as 1.0 M aqueous NaCl, KCl, CaCl2, and
      MgCl2 solutions. TEM observations showed self-assembled fibers with diameters of
      10-100 nm. FT-IR results revealed that the gels were mainly formed by hydrogen
      bonding and van der Waals forces; thixotropic behavior resulted from the
      disruption of the van der Waals forces between the alkylene chains under
      shearing. These results were repeatedly and reproducibly observed at room
      temperature, even when measurements were repeated many times.

PMID- 24131484
TI  - Current drivers and geographic patterns of HIV in Lesotho: implications for
      treatment and prevention in Sub-Saharan Africa.
AB  - BACKGROUND: The most severe HIV epidemics worldwide occur in Lesotho, Botswana
      and Swaziland. Here we focus on the Lesotho epidemic, which has received little
      attention. We determined the within-country heterogeneity in the severity of the
      epidemic, and identified the risk factors for HIV infection. We also determined
      whether circumcised men in Lesotho have had a decreased risk of HIV infection in
      comparison with uncircumcised men. We discuss the implications of our results for
      expanding treatment (current coverage is only 60%) and reducing transmission.
      METHODS: We used data from the 2009 Lesotho Demographic and Health Survey, a
      nationally representative survey of 3,849 women and 3,075 men in 9,391
      households. We performed multivariate analysis to identify factors associated
      with HIV infection in the sexually active population and calculated age-adjusted
      odds ratios (aORs). We constructed cartographic country-level prevalence maps
      using geo-referenced data. RESULTS: HIV is hyperendemic in the general
      population. The average prevalence is 27% in women and 18% in men, but shows
      substantial geographic variation. Throughout the country prevalence is higher in
      urban centers (31% in women; 21% in men) than in rural areas (25% in women; 17%
      in men), but the vast majority of HIV-infected individuals live in rural areas.
      Notably, prevalence is extremely high in women (18%) and men (12%) with only one
      lifetime sex partner. Women with more partners have a greater risk of infection:
      aOR 2.3 (2 to 4 partners), aOR 4.4 (>=5 partners). A less substantial effect was
      found for men: aOR 1.4 (3 to 6 partners), aOR 1.8 (>=7 partner). Medical
      circumcision protected against infection (aOR 0.5), traditional circumcision did
      not (aOR 0.9). Less than 5% of men in Lesotho have been medically circumcised;
      approximately 50% have been circumcised using traditional methods. CONCLUSIONS:
      There is a substantial need for treatment throughout Lesotho, particularly in
      rural areas where there is the greatest burden of disease. Interventions aimed at
      reducing the number of sex partners may only have a limited effect on reducing
      transmission. Substantially increasing levels of medical circumcision could be
      very effective in reducing transmission, but will be very difficult to achieve
      given the current high prevalence of traditional circumcision.

PMID- 24131485
TI  - A phase I study on combined therapy with proton-beam radiotherapy and in situ
      tumor vaccination for locally advanced recurrent hepatocellular carcinoma.
AB  - BACKGROUND: Proton-beam radiotherapy (PBT) has been shown to be effective to
      hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However,
      HCC still remains as one of the most difficult cancers to be cured because of
      frequent recurrences. Thus, methods to inhibit the recurrence need to be
      explored. To prevent the HCC recurrence, we here report on a prospective phase I
      study of 'in situ' tumor vaccination using CalTUMP, a newly developed
      immunoadjuvant consisting of BCG extract bound to hydroxyapatite and
      microparticulated tuberculin, following local PBT for HCC. METHODS: Patients with
      locally advanced recurrent HCC, which had been heavily pretreated with various
      treatments, were enrolled. PBT was performed with the conventional method to the
      target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor
      three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and
      1/1) were administered to 3 patients each. Vital signs, blood samples,
      ultrasound, and computed tomographic scans were monitored to evaluate the safety.
      RESULTS: Three intratumoral injections of CalTUMP following PBT (median dose:
      72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor
      laboratory changes were observed in 7 patients after CalTUMP injections. No other
      treatment-related adverse events were observed. Median progression-free survival
      was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more
      than 1 year. CONCLUSIONS: Intratumoral injection of CalTUMP following PBT was
      feasible and safe in patients with heavily pre-treated HCC. Further clinical
      studies to evaluate the efficacy of this in situ tumor vaccination are warranted.

PMID- 24131486
TI  - Induction of proliferation and pro-inflammatory cytokine production in rheumatoid
      arthritis peripheral blood mononuclear cells by a 65 KDa chondrocyte membrane
      specific, constitutive target autoantigen (CH65).
AB  - OBJECTIVE: To analyze proliferation and pro-inflammatory cytokine production of
      peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients
      following stimulation with a purified chondrocyte membrane-associated autoantigen
      (CH65). METHODS: CH65 was highly purified from bovine chondrocyte membranes by
      solubilization and ion exchange chromatography. PBMC of RA patients (n = 37; 28
      seropositive, nine seronegative) and non-arthritic donors (n = 20) were isolated
      by ficoll centrifugation and used in cell proliferation assays. The levels of
      interleukin (IL)-1, tumo necrosis factor (TNF) and IL-6 produced after
      stimulation with CH65 were determined by enzyme-linked immunosorbent assay
      (ELISA). Statistical analysis was performed using Mann-Whitney U-test and
      Spearman rank test and the software SPSS 13.0TM (SPSS Inc.; Chicago, IL, USA).
      RESULTS: Peripheral blood mononuclear cells exhibited a strong proliferative
      response to purified CH65 in approximately 50% of the RA patients (seropositive >
      seronegative), with a maximum reactivity at 0.15 or 0.30 MUg/mL culture medium.
      In contrast, PBMC from normal donors did not show a proliferative response to
      CH65 at any dose. The proliferative response in RA patients peaked at days 7-9
      and returned to control levels at day 13, indicating an antigen-driven process.
      CH65-stimulated RA PBMC produced moderate to high amounts of IL-1, TNF and IL-6.
      This was comparable to the response after exposure to isolated whole chondrocyte
      membranes or purified collagen type II. CONCLUSION: These results demonstrate a
      significant cellular immune response to CH65 protein in RA patients. Given the
      high similarity between bovine and human CH65, the results suggest a pathogenetic
      involvement of this molecule as a cartilage-specific potential target autoantigen
      in RA.

PMID- 24131487
TI  - Farewell to an old friend: chest X-ray vs high-resolution computed tomography in
      welders' lung disease.
AB  - INTRODUCTION: Welder's lung disease originated from a mixed exposure to different
      kinds of metals and chemicals from welding fumes. Because of these various
      harmful effects, irreversible morphological changes may occur in all parts of the
      respiratory tract, airways and lung parenchyma. Parenchymal changes are the main
      lesions that define the severity of exposure. The grade of these lesions is the
      main criteria for compensation claims and the clinical threshold for the
      occupational health physician's decision making of work change in order to
      protect the worker's health. In this study, our aim was to compare the diagnostic
      performance of chest X-ray (CXR) and high-resolution computed tomography (HRCT)
      for welders' lung disease. OBJECTIVES: Seventy-four male welders aged between 25
      and 55 years were enrolled to this study. METHODS: Clinical diagnoses were
      compared by CXR and HRCT. Same radiologists evaluated the scans without any
      knowledge about the medical history of the patient (double-blinded evaluation).
      The agreement between radiologists was compared with Cohen's kappa statistics.
      RESULTS: The mean age for 74 welders was 40.7 years. The mean duration of
      exposure was 18.9 years. Although all were found to be nonpathological on the
      CXR, 27 mild nodular and nine mild linear opacities, five emphysematous changes,
      three ground glass infiltrates and one pleural thickening were detected by HRCT.
      CONCLUSIONS: HRCT provides better diagnostic performance compared to CXR for the
      diagnosis of welders' lung disease.

PMID- 24131488
TI  - Photoactivated colloidal dockers for cargo transportation.
AB  - We introduce a self-propelled colloidal hematite docker that can be steered to a
      small particle cargo many times its size, dock, transport the cargo to a remote
      location, and then release it. The self-propulsion and docking are reversible and
      activated by visible light. The docker can be steered either by a weak uniform
      magnetic field or by nanoscale tracks in a textured substrate. The light
      activated motion and docking originate from osmotic/phoretic particle transport
      in a concentration gradient of fuel, hydrogen peroxide, induced by the
      photocatalytic activity of the hematite. The docking mechanism is versatile and
      can be applied to various materials and shapes. The hematite dockers are simple
      single-component particles and are synthesized in bulk quantities. This system
      opens up new possibilities for designing complex micrometer-size factories as
      well as new biomimetic systems. 

PMID- 24131489
TI  - Risk of colorectal cancer in women with pelvic inflammatory disease: a matched
      cohort study.
AB  - OBJECTIVE: Inflammation is an important risk factor for the development of
      colorectal cancer (CRC). Pelvic inflammatory disease (PID) comprises a spectrum
      of upper genital tract infections and inflammatory diseases. We aimed to evaluate
      the association between CRC and PID. DESIGN: Matched cohort study using the
      National Health Insurance Research Database. SETTING: Women with PID in Taiwan.
      POPULATION AND SAMPLE: From the Longitudinal Health Insurance Database 2005
      (LHID2005) in Taiwan, we obtained data on women from 13 to 45 years of age who
      were diagnosed with PID. The women with PID were matched 1:4 to selected members
      of the population without PID based on age and year of first entry into the
      LHID2005. METHODS: A Cox proportional hazards model was used to evaluate the
      hazard ratio for CRC during the 5-year follow-up period, after adjusting for
      sociodemographic characteristics and selected comorbid medical disorders. MAIN
      OUTCOME MEASURES: Colorectal cancer. RESULTS: Of the 19,029 women with PID, 30
      were diagnosed with CRC during the 78,965 person-year follow-up period. Of the
      76,116 control women, 66 were diagnosed with CRC. The CRC hazard ratio during the
      5-year follow-up period was 2.00 (95% CI 1.30-3.08) for women with PID relative
      to control women. Similarly, after adjusting for age, Charlson comorbidity index
      score, urbanisation level and monthly income, the adjusted CRC hazard ratio was
      1.71 (95% CI 1.10-2.65) for the women with PID relative to the women in the
      comparison cohort. CONCLUSIONS: Here we show a weak association between PID and
      CRC. Additional studies are needed to further evaluate this association and
      examine plausible mechanisms, including the influence of specific microorganisms.

PMID- 24131490
TI  - Fasting and postprandial volumes of the undisturbed colon: normal values and
      changes in diarrhea-predominant irritable bowel syndrome measured using serial
      MRI.
AB  - BACKGROUND: Previous assessments of colon morphology have relied on tests which
      were either invasive or used ionizing radiation. We aimed to measure regional
      volumes of the undisturbed colon in healthy volunteers (HV) and patients with
      diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: 3D regional
      (ascending, transverse, and descending) colon volumes were measured in fasting
      abdominal magnetic resonance (MR) images of 75 HVs and 25 IBS-D patients. Thirty
      five of the HV and all 25 IBS-D subjects were fed a standard meal and
      postprandial MRI data obtained over 225 min. KEY RESULTS: Colonic regions were
      identified and 3D maps from cecum to sigmoid flexure were defined. Fasted
      regional volumes showed wide variation in both HVs being (mean +/- SD) ascending
      colon (AC) 203 +/- 75 mL, transverse (TC) 198 +/- 79 mL, and descending (DC) 160
      +/- 86 mL with no difference from IBS-D subjects (AC 205 +/- 69 mL, TC 232 +/-
      100 mL, and DC 151 +/- 71 mL, respectively). The AC volume expanded by 10% after
      feeding (p = 0.007) in the 35 HV possibly due to increased ileo-colonic inflow. A
      later rise in AC volume occurred from t = 90 to t = 240 min as the meal residue
      entered the cecum. In contrast, IBS-D subjects showed a much reduced postprandial
      response of the AC (p < 0.0001) and a greater increase in TC volume after 90 min
      (p = 0.0244) compared to HV. CONCLUSIONS & INFERENCES: We have defined a normal
      range of the regional volumes of the undisturbed colon in fasted and fed states.
      The AC in IBS-D appeared less able to accommodate postprandial inflow which may
      account for faster colonic transit.

PMID- 24131491
TI  - Enhanced tumor retention of a radiohalogen label for site-specific modification
      of antibodies.
AB  - A known limitation of iodine radionuclides for labeling and biological tracking
      of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse
      from cells following endocytosis and lysosomal degradation. In contrast,
      radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the
      residualizing properties of the polar, charged metal-chelate-amino acid adduct.
      Iodine radionuclides boast a diversity of nuclear properties and chemical means
      for incorporation, prompting efforts to covalently link radioiodine with
      residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I
      125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and
      demonstration of its residualizing properties in a murine xenograft model.
      Overall, this study displays the power of multicomponent synthesis to yield a
      versatile radioactive probe for antibodies across multiple therapeutic areas with
      potential applications in both preclinical biodistribution studies and clinical
      radioimmunotherapies. 

PMID- 24131492
TI  - Visualizing the subsurface of soft matter: simultaneous topographical imaging,
      depth modulation, and compositional mapping with triple frequency atomic force
      microscopy.
AB  - Characterization of subsurface morphology and mechanical properties with
      nanoscale resolution and depth control is of significant interest in soft matter
      fields like biology, polymer science, and even in future applications like
      nanomanufacturing, where buried structural and compositional features are
      important to the functionality of the system. However, controllably "feeling" the
      subsurface is a challenging task for which the available imaging tools are
      relatively limited. In this paper, we propose a trimodal atomic force microscopy
      (AFM) imaging scheme, whereby three eigenmodes of the microcantilever probe are
      used as separate control "knobs" to simultaneously measure the topography,
      modulate sample indentation by the tip during tip-sample impact, and map
      compositional contrast, respectively. We illustrate this multifrequency imaging
      approach through computational simulation and experiments conducted on ultrathin
      polymer films with embedded glass nanoparticles in ambient air. By actively
      increasing the tip-sample indentation using a higher eigenmode of the cantilever,
      we are able to gradually and controllably reveal glass nanoparticles which are
      buried tens of nanometers deep under the surface, while still being able to
      refocus on the surface. 

PMID- 24131493
TI  - Marked seasonality of aerobic anoxygenic phototrophic bacteria in the coastal NW
      Mediterranean Sea as revealed by cell abundance, pigment concentration and
      pyrosequencing of pufM gene.
AB  - The abundance and diversity of aerobic anoxygenic phototrophs (AAPs) were studied
      for a year cycle at the Blanes Bay Microbial Observatory (NW Mediterranean) and
      their potential links to an array of environmental variables were explored. Cell
      numbers were low in winter and peaked in summer, showing a marked seasonality
      that positively correlated with day length and light at the surface.
      Bacteriochlorophyll a concentration, their light-harvesting pigment, was only
      detected between April and October, and pigment cell quota showed large
      variations during this period. Pyrosequencing analysis of the pufM gene revealed
      that the most abundant operational taxonomic units (OTUs) were affiliated to
      phylogroup K (Gammaproteobacteria) and uncultured phylogroup C, although they
      were outnumbered by alphaproteobacterial OTUs in spring. Overall, richness was
      higher in winter than in summer, showing an opposite trend to abundance and day
      length. Clustering of samples by multivariate analyses showed a clear seasonality
      that suggests a succession of different AAP subpopulations over time.
      Temperature, chlorophyll a and day length were the environmental drivers that
      best explained the distribution of AAP assemblages. These results indicate that
      AAP bacteria are highly dynamic and undergo seasonal variations in diversity and
      abundance mostly dictated by environmental conditions as exemplified by light
      availability. 

PMID- 24131494
TI  - Replacement of the st jude medical regent valve in the aortic position with a
      continuous suture technique in the small aortic root.
AB  - BACKGROUND: The aim of this study is to review the strategy of performing aortic
      valve replacement (AVR) by using the St. Jude Medical (SJM) Regent valve with a
      continuous suture technique in patients with a small aortic root. METHODS: Forty
      six patients with small aortic annulus underwent AVR by using 19 or 21 mm SJM
      Regent valves. There were 15 males and 31 females. The mean age of the patients
      was 51.8 +/- 12.4 years. The aortic annular diameter was 20.2 +/- 0.9 mm. AVR
      procedures were performed with continuous suture technique using SJM Regent
      valves under standard cardiopulmonary bypass. Echocardiaographic data were
      collected before operation, at discharge, and at a follow-up time, respectively.
      RESULTS: The intraoperative course was uneventful and there was no operative
      mortality. The implanted SJM Regent valves consisted of 21 mm valves in 15
      patients and 19 mm valves in 31 patients. Echocardiography at 5.6 +/- 1.3 months
      after operation showed a significant increase in the mean effective orifice area
      index (0.97 +/- 0.24 cm(2) /m(2) ), decrease in the mean and peak transvavluar
      pressure gradient (12.5 +/- 5.9 and 22.3 +/- 9.6 mmHg), and decrease in the mean
      left ventricular mass index (106 +/- 41.3 g/m(2) ). Moderate prosthesis-patient
      mismatch (PPM) (effective orifice area index between 0.65 and 0.85 cm(2) /m(2) )
      was present in three patients and no severe PPM (effective orifice area index
      <0.65 cm(2) /m(2) ) occurred at discharge and during follow-up. CONCLUSION:
      Replacement of SJM Regent valve with a continuous suture technique maybe a good
      option to prevent PPM in the aortic position.

PMID- 24131495
TI  - An individualised treatment algorithm for tumour stage 1 glottic squamous cell
      carcinoma.
AB  - OBJECTIVE: To report and discuss the outcome of a treatment algorithm for
      patients with tumour stage 1 glottic squamous cell carcinoma. METHOD: A
      retrospective outcome analysis study was performed using data from a tertiary
      referral centre. RESULTS: Sixty-nine patients were treated with radiotherapy and
      26 with surgery, in accordance with the treatment algorithm. Five-year overall
      survival rates were the same for both treatment groups (92 per cent). Five-year
      disease-specific survival rates were 100 per cent for surgery, 98 per cent for
      radiotherapy and 99 per cent overall. The overall 5-year laryngeal preservation
      rate was 89.1 per cent, being 95.7 per cent for surgery patients and 86.7 per
      cent for radiotherapy patients (p = 0.502). There was no significant association
      between laryngeal preservation rates and age (p = 0.779), anterior commissure
      involvement (p = 0.081), tumour stage (1a or 1b) (p = 0.266) or treatment
      modality (surgery or radiotherapy; p = 0.220). There was no significant
      difference in local recurrence rates between the two treatment groups (19.3 per
      cent for radiotherapy vs 10.0 per cent for surgery; p = 0.220). The overall 5
      year regional recurrence rate was 1.2 per cent. CONCLUSION: Tumour stage 1
      glottic carcinoma can be managed with different treatment modalities, following
      an individualised treatment algorithm, with results comparable to published
      outcomes.

PMID- 24131496
TI  - Improving physical health and reducing substance use in psychosis--randomised
      control trial (IMPACT RCT): study protocol for a cluster randomised controlled
      trial.
AB  - BACKGROUND: Cardiovascular morbidity and mortality is increased in individuals
      with severe mental illnesses.We set out to establish a multicentre, two arm,
      parallel cluster randomized controlled trial (RCT) of a health promotion
      intervention (HPI), IMPACT Therapy. The patient-tailored IMPACT Therapy aims to
      target one or more health behaviours from a pre-defined list that includes
      cannabis use; alcohol use; other substance use; cigarette smoking; exercise; diet
      and diabetic control, prioritising those identified as problematic by the
      patient, taking a motivational interviewing and CBT approach. METHODS: Impact
      therapy will be delivered by care coordinators in the community to the treatment
      group and will be compared to treatment as usual (TAU). The main hypothesis is
      that the addition of IMPACT Therapy (HPI) to TAU will be more effective than TAU
      alone in improving patients' quality of life as measured by the Short Form-36,
      including mental health and physical health subscales on completion of the
      intervention at 12 months post randomisation. A subsidiary hypothesis will be
      that addition of IMPACT Therapy (HPI) will be more cost-effective than TAU alone
      in improving health in people with SMI 12 months from baseline. The IMPACT
      therapy patient groups' improvement in quality of life, as well as its cost
      effectiveness, is hypothesised to be maintained at 15 months. Outcomes will be
      analyzed on an intention-to-treat (ITT) basis. DISCUSSION: The results of the
      trial will provide information about the effectiveness of the IMPACT therapy
      programme in supporting community mental health teams to address physical
      comorbidity in severe mental illness. TRIAL REGISTRATION: ISRCTN58667926.

PMID- 24131497
TI  - Structural brain abnormalities in cervical dystonia.
AB  - BACKGROUND: Idiopathic cervical dystonia is characterized by involuntary spasms,
      tremors or jerks. It is not restricted to a disturbance in the basal ganglia
      system because non-conventional voxel-based MRI morphometry (VBM) and diffusion
      tensor imaging (DTI) have detected numerous regional changes in the brains of
      patients.In this study scans of 24 patients with cervical dystonia and 24 age-and
      sex-matched controls were analysed using VBM, DTI and magnetization transfer
      imaging (MTI) using a voxel-based approach and a region-of-interest analysis.
      Results were correlated with UDRS, TWSTRS and disease duration. RESULTS: We found
      structural alterations in the basal ganglia; thalamus; motor cortex; premotor
      cortex; frontal, temporal and parietal cortices; visual system; cerebellum and
      brainstem of the patients with dystonia. CONCLUSIONS: Cervical dystonia is a
      multisystem disease involving several networks such as the motor, sensory and
      visual systems.

PMID- 24131499
TI  - Experience of BRCA1/2 mutation-negative young women from families with hereditary
      breast and ovarian cancer: a qualitative study.
AB  - BACKGROUND: Little is known about the experience of young women who become aware
      of their parent's BRCA1 or BRCA2 (BRCA) mutation status as adolescents or young
      adults. There is also currently a gap in the literature pertaining to those who
      are found to be negative for their familial mutation. We aimed to investigate the
      experience of these mutation-negative young women from hereditary breast and
      ovarian cancer (HBOC) families. METHODS: Using a semi-structured questionnaire we
      interviewed 8 women. All of the women were non-carriers of their familial
      mutation and had learned of the mutation in their family as adolescents or young
      adults at least 6 months prior to undergoing genetic testing. All interviews were
      audio recorded, transcribed, and independently analyzed by the investigators.
      This was followed by an in-depth cross-case analysis, enabling the formulation of
      emergent themes. RESULTS: The women's age ranged from 22 to 37 years old and all
      were of Ashkenazi Jewish descent. Prominent emergent themes from the interviews
      included the impact of how and when the familial mutation status was disclosed,
      the factors influencing when a young woman chooses to undergo predictive genetic
      testing, the predictors of post-test adjustment and risk perception, as well as
      the impact of familial cancer experience versus the familial mutation.
      CONCLUSIONS: By eliciting detailed patient narratives we have begun to show that
      this generation of BRCA mutation-negative young women is likely still affected by
      the degree of cancer history in their family, even with their understanding of
      the genetic contribution to disease. Larger studies with tightened participant
      characteristics, as well as studies involving women from different cultural
      backgrounds, are needed to further define the experience and needs of true
      negative young women from HBOC families.

PMID- 24131500
TI  - Association of FcgammaRIIIa-158V/F with systemic lupus erythematosus in a Chinese
      population.
AB  - AIM: It has long been a controversy that polymorphisms in FcgammaRIIIa (CD16A)
      receptors are associated with systemic lupus erythematosus (SLE). We aimed to
      verify the association of FcgammaRIIIa polymorphisms with SLE in a large Chinese
      population. METHODS: We genotyped FcgammaRIIIa-158V/F (rs396991) using a pyro
      sequencing assay (PSQ 96MA) in a total of 732 individuals with SLE (390 lupus
      nephritis and 342 non-lupus nephritis) and 886 controls. Meta-analysis was used
      to examine the association of the FcgammaRIIIa-F158 allele with SLE and lupus
      nephritis with RevMan 5. RESULTS: The allele frequencies of FcgammaRIIIa-F158
      were significantly increased in SLE (OR 1.293, 95%CI 1.111-1.505, P = 0.0009).
      There was significant skewing in the distribution of FcgammaRIIIa genotypes
      between SLE patients and controls (P = 0.0026 for 158 F/F vs. 158F/V and 158V/V,
      OR 1.604, 95%CI 1.089-2.361). Serositis was more common in patients with the
      FcgammaRIIIa-F158 allele and FcgammaRIIIa-F/F genotype, and low complement was
      more common in patients with the FcgammaRIIIa-F/F genotype. There was no skewing
      in the distribution of FcgammaRIIIa genotypes in the lupus nephritis group. No
      association was found for the frequencies of the FcgammaRIIIa-F158 allele and
      158F/F genotype compared with the V158 allele and F/V plus V/V genotypes,
      respectively, between lupus nephritis and SLE without nephritis patients in a
      meta-analysis of 11 Asian studies. CONCLUSION: Our results suggest that the low
      binding allele FcgammaRIIIa-158F is one of the risk factors for SLE in the
      Chinese population.

PMID- 24131498
TI  - Expression profile of host restriction factors in HIV-1 elite controllers.
AB  - BACKGROUND: Several host-encoded antiviral factors suppress HIV-1 replication in
      a cell-autonomous fashion in vitro. The relevance of these defenses to the
      control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular
      restriction of HIV-1 replication plays a significant role in the observed
      suppression of HIV-1 in "elite controllers", individuals who maintain
      undetectable levels of viremia in the absence of antiretroviral therapy (ART). We
      comprehensively compared the expression levels of 34 host restriction factors and
      cellular activation levels in CD4+ T cells and sorted T cell subsets between
      elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed,
      and uninfected individuals. RESULTS: Expression of schlafen 11, a codon usage
      based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T
      cells from elite controllers as compared to both non-controllers (p = 0.048) and
      ART-suppressed individuals (p = 0.024), with this effect most apparent in central
      memory CD4+ T cells. Schlafen 11 expression levels were comparable between
      controllers and uninfected individuals. Cumulative restriction factor expression
      was positively correlated with CD4+ T cell activation (r2 = 0.597, p < 0.0001),
      viral load (r2 = 0.34, p = 0.015), and expression of ISG15 (r2 = 0.73, p <
      0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and
      TRIM32 were elevated in elite controllers with respect to ART-suppressed
      individuals, while levels were comparable to uninfected individuals and non
      controllers. CONCLUSIONS: Host restriction factor expression typically scales
      with cellular activation levels. However, the elevated mRNA and protein
      expression of schlafen 11, despite low activation and viral load, violates the
      global pattern and may be a signature characteristic of HIV-1 elite control.

PMID- 24131501
TI  - Determinants of child and forced marriage in Morocco: stakeholder perspectives on
      health, policies and human rights.
AB  - BACKGROUND: In Morocco, the social and legal framework surrounding sexual and
      reproductive health has transformed greatly in the past decade, especially with
      the introduction of the new Family Law or Moudawana. Yet, despite raising the
      minimum age of marriage for girls and stipulating equal rights in the family,
      child and forced marriage is widespread. The objective of this research study was
      to explore perspectives of a broad range of professionals on factors that
      contribute to the occurrence of child and forced marriage in Morocco. METHODS: A
      qualitative approach was used to generate both primary and secondary data for the
      analysis. Primary data consist of individual semi-structured interviews that were
      conducted with 22 professionals from various sectors: health, legal, education,
      NGO's and government. Sources of secondary data include academic papers,
      government and NGO reports, various legal documents and media reports. Data were
      analyzed using thematic qualitative analysis. RESULTS: Four major themes arose
      from the data, indicating that the following elements contribute to child and
      forced marriage: (1) the legal and social divergence in conceptualizing forced
      and child marriage; (2) the impact of legislation; (3) the role of education; and
      (4) the economic factor. Emphasis was especially placed on the new Family Code or
      Moudawana as having the greatest influence on advancement of women's rights in
      the sphere of marriage. However, participants pointed out that embedded
      patriarchal attitudes and behaviours limit its effectiveness. CONCLUSION: The
      study provided a comprehensive understanding of the factors that compound the
      problem of child and forced marriage in Morocco. From the viewpoint of
      professionals, who are closely involved in tackling the issue, policy measures
      and the law have the greatest potential to bring child and forced marriage to a
      halt. However, the implementation of new legal tools is facing barriers and
      resistance. Additionally, the legal and policy framework should go hand in hand
      with both education and increased economic opportunities. Education and awareness
      raising of all ages is considered essential, seeing that parents and the extended
      family play a huge role in marrying off girls and young women.

PMID- 24131502
TI  - High prevalence of human metapneumovirus subtype B in cases presenting as severe
      acute respiratory illness: an experience at tertiary care hospital.
AB  - PURPOSE: A comparatively newly discovered human metapneumovirus (HMPV) has
      emerged as an important cause of severe acute respiratory illness (SARI), second
      only to respiratory syncytial virus (RSV). RSV and HMPV taxonomically belong to
      same family and subfamily, and their clinical presentation and seasonal
      distribution are also seemed to be indistinguishable. Present study was planned
      to know the epidemiology and prevalence of HMPV and RSV in patients presented as
      SARI in a tertiary care hospital. METHODS: Nasopharyngeal aspirate of 440
      patients fulfilling World Health Organization criteria of SARI, enrolled during a
      2-year study period, were collected and tested for the presence of RSV, HMPV and
      their subtypes A and B by real time polymerase chain reaction along with other
      respiratory viruses, viz influenza A, B, parainfluenza 1, 2, 3, 4, adenovirus,
      measles virus and bocavirus. The demographic details, clinical profile,
      underlying diseases, clinical diagnosis at the time of admission and seasonal
      distribution were studied and analyzed statistically. RESULTS: Overall positivity
      of RSV was 14.3% (24.68% in <5 years) and of HMPV was 3.63% (5.1% in <5 years and
      5.08% in 6-12 years). Among RSV, subtype A (89%), and among HMPV, genotype B
      (68.8%) were predominating. Adults having underlying chronic obstructive
      pulmonary disease were more prone to acquire RSV and HMPV infections. RSV and
      HMPV positivity was restricted to winter season. We are reporting replacement of
      RSV with HMPV in this population. CONCLUSIONS: HMPV has emerged as an important
      cause of SARI in children <12 years of age. Alternative predominance of RSV and
      HMPV is an important observation.

PMID- 24131503
TI  - Stereotactic body radiotherapy in the treatment of pancreatic adenocarcinoma in
      elderly patients.
AB  - BACKGROUND: Treatment of pancreatic adenocarcinoma in the elderly is often
      complicated by comorbidities that preclude surgery, chemotherapy and/or
      conventional external beam radiation therapy (EBRT). Stereotactic body
      radiotherapy (SBRT) has thus garnered interest in this setting. METHODS: A
      retrospective review of 26 patients of age >= 80 with pancreatic adenocarcinoma
      treated with definitive SBRT+/-chemotherapy from 2007-2011 was performed. Twenty
      seven percent of patients were stage I, 38% were stage II, 27% were stage III and
      8% were stage IV. Patients most commonly received 24 Gy/1 fraction or 30-36 Gy/3
      fractions. Kaplan-Meier was used to estimate overall survival (OS), local control
      (LC), cause specific survival (CSS) and freedom-from-metastatic disease (FFMD).
      RESULTS: The median age was 86 (range 80-91), and median follow-up was 11.6
      months (3.5-24.6). The median planning target volume was 21.48 cm3 (6.1-85.09).
      Median OS was 7.6 months with 6/12 month OS rates of 65.4%/34.6%, respectively.
      Median LC was 11.5 months, 6-month and 12-month actuarial LC rates were 60.1% and
      41.2%, respectively. There were no independent predictors for LC, but there was a
      trend for improved LC with prescription dose greater than 20 Gy (p = 0.063).
      Median CSS was 6.3 months, and 6-month and 12-month actuarial CSS were 53.8% and
      23.1%, respectively. Median FFMD was 8.4 months, and 6-month and 12-month
      actuarial rates were 62.0% and 41.4%, respectively. Nine patients (47%) had local
      failures, 11 (58%) had distant metastasis, and 7 (37%) had both. There were no
      acute or late grade 3+ toxicities. CONCLUSIONS: Definitive SBRT is feasible, safe
      and effective in elderly patients who have unresectable disease, have
      comorbidities precluding surgery or decline surgery.

PMID- 24131504
TI  - Scintigraphic assessment of gastrointestinal motility: a brief review of
      techniques and data interpretation.
AB  - Gastrointestinal transit reflects overall gastrointestinal motor activity and is
      regulated by a complex interplay between neural and hormonal stimuli. Thus,
      transit measurements provide a measure of the combined effects of
      gastrointestinal muscular activity and feedback from the gut and brain.
      Dysmotility in the different major segments of the gastrointestinal tract may
      give rise to similar symptoms; hence, localizing transit abnormalities to a
      specific segment is a valuable element of diagnostic evaluation. Scintigraphy is
      an effective noninvasive tool to assess gastric emptying as well as small
      intestinal and colonic transit. This article reviews current imaging techniques,
      methods for data processing and principles for evaluating results when
      scintigraphy is used to assess gastrointestinal motility. Furthermore, clinical
      indications for performing scintigraphy are reviewed. 

PMID- 24131505
TI  - Principles and guidelines for early intervention after confirmation that a child
      is deaf or hard of hearing.
AB  - This document is a supplement to the year 2007 position statement of the Joint
      Committee on Infant Hearing and provides comprehensive guidelines for
      establishing strong early intervention (EI) systems with appropriate expertise to
      meet the needs of children who are deaf or hard of hearing (D/HH). Optimal
      outcomes can only be achieved when there is high quality to the universal newborn
      hearing screening programs, the audiologic diagnostic process of confirmation
      that a child is D/HH and fitting of amplification, and the provision of
      appropriate, individualized, targeted, and high-quality EI services. There are 12
      best practice guidelines for EI programs that include the provision of timely
      referral to EI services with providers who have knowledge and skills in early
      childhood deafness and hearing loss, infusion within the system of partnerships
      with parents as well as professionals who are D/HH, longitudinal developmental
      assessments for monitoring the child's development, data management systems that
      include developmental outcomes, a process to monitor the fidelity of the
      intervention, and appropriate services for children with additional disabilities,
      those from non-English speaking families, and those from special populations,
      including unilateral hearing loss and auditory neuropathy/dyssynchrony. 

PMID- 24131506
TI  - Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic
      hepatitis C: final analysis from the PROPHESYS cohort.
AB  - The population of patients with chronic hepatitis C viral infection is ageing;
      however, elderly, hepatitis C-infected patients are understudied and less
      frequently treated. This subanalysis of data from the multinational PROPHESYS
      study examined associations between age (<=65 vs >65 years), on-treatment
      virological response and sustained virological response (SVR) in patients treated
      with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences.
      PROPHESYS comprised three cohorts studied in 19 countries according to country
      specific legal and regulatory requirements. This subanalysis includes treatment
      naive HCV mono-infected patients assigned to receive peginterferon alfa-2a
      (40KD)/ribavirin, with 6276 individuals aged <=65 years and 349 aged >65 years.
      Rapid virological response (RVR) rates by Week 4 were consistently lower in older
      genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3
      (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%)
      and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P =
      0.0002 vs <=65 years). In contrast, SVR and relapse rates were similar in G2 and
      G3 patients regardless of age. The positive predictive value of RVR for SVR was
      comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and
      higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological
      response rates are generally lower in elderly CHC patients, and RVR is a reliable
      positive predictor of SVR in patients >65 years. 

PMID- 24131507
TI  - Proteomic characterization of the acid tolerance response in Lactobacillus
      delbrueckii subsp. bulgaricus CAUH1 and functional identification of a novel acid
      stress-related transcriptional regulator Ldb0677.
AB  - To overcome the deleterious effects of acid stress, Lactobacillus delbrueckii
      subsp. bulgaricus (L. bulgaricus) elicits an adaptive response to acid stress. In
      this study, proteomics approach complemented by transcriptional analysis revealed
      some cellular changes in L. bulgaricus CAUH1 during acid adaptation. We observed
      an increase of glycolysis-associated proteins, promoting an optimal utilization
      of carbohydrates. Also, rerouting of the pyruvate metabolism to fatty acid
      biosynthesis was observed, indicating a possible modification of the cell
      membrane rigidity and impermeability. In addition, expression of ribosomal
      protein S1 (RpsA) was repressed; however, the expression of EF-Tu, EF-G and TypA
      was up-regulated at both protein and transcript levels. This suggests a reduction
      of protein synthesis in response to acid stress along with possible enhancement
      of the translational accuracy and protein folding. It is noteworthy that the
      putative transcriptional regulator Ldb0677 was 1.84-fold up-regulated.
      Heterologous expression of Ldb0677 was shown to significantly enhance acid
      resistance in host strain Lactococcus lactis. To clarify its role in
      transcriptional regulation network, the DNA-binding specificity of Ldb0677 was
      determined using bacterial one-hybrid and electrophoretic mobility shift assay.
      The identification of a binding motif (SSTAGACR) present in the promoter regions
      of 22 genes indicates that it might function as a major regulator in acid stress
      response in L. bulgaricus.

PMID- 24131508
TI  - Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory
      peptides for the management of type 2 diabetes.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) is increasing and it is
      estimated that by 2030 approximately 366 million people will be diagnosed with
      this condition. The use of dipeptidyl peptidase IV (DPP-IV) inhibitors is an
      emerging strategy for the treatment of T2DM. DPP-IV is a ubiquitous
      aminodipeptidase that cleaves incretins such as glucagon like peptide 1 (GLP-1)
      and glucose-dependent insulinotropic polypeptide (GIP), resulting in a loss in
      their insulinotropic activity. Synthetic DPP-IV drug inhibitors are being used to
      increase the half-life of the active GLP-1 and GIP. Dietary intervention is
      accepted as a key component in the prevention and management of T2DM. Therefore,
      identification of natural food protein-derived DPP-IV inhibitors is desirable.
      Peptides with DPP-IV inhibitory activity have been identified in a variety of
      food proteins. This review aims to provide an overview of food protein
      hydrolysates as a source of the DPP-IV inhibitory peptides with particular focus
      on milk proteins. In addition, the proposed modes of inhibition and structure
      activity relationship of peptide inhibitors are discussed. Milk proteins and
      associated peptides also display insulinotropic activity and help regulate blood
      glucose in healthy and diabetic subjects. Therefore, milk protein derived peptide
      inhibitors may be a unique multifunctional peptide approach for the management of
      T2DM. 

PMID- 24131509
TI  - Incidence of catheter-related complications in patients with central venous or
      hemodialysis catheters: a health care claims database analysis.
AB  - BACKGROUND: Central venous catheter (CVC) and hemodialysis (HD) catheter usage
      are associated with complications that occur during catheter insertion, dwell
      period, and removal. This study aims to identify and describe the incidence rates
      of catheter-related complications in a large patient population in a United
      States-based health care claims database after CVC or HD catheter placement.
      METHODS: Patients in the i3 InVision DataMart(r) health care claims database with
      at least 1 CVC or HD catheter insertion claim were categorized into CVC or HD
      cohorts using diagnostic and procedural codes from the US Renal Data System,
      American College of Surgeons, and American Medical Association's Physician
      Performance Measures. Catheter-related complications were identified using
      published diagnostic and procedural codes. Incidence rates (IRs)/1000 catheter
      days were calculated for complications including catheter-related bloodstream
      infections (CRBSIs), thrombosis, embolism, intracranial hemorrhage (ICH), major
      bleeding (MB), and mechanical catheter-related complications (MCRCs). RESULTS:
      Thirty percent of the CVC cohort and 54% of the HD cohort had catheter placements
      lasting <90 days. Catheter-related complications occurred most often during the
      first 90 days of catheter placement. IRs were highest for CRBSIs in both cohorts
      (4.0 [95% CI, 3.7-4.3] and 5.1 [95% CI, 4.7-5.6], respectively). Other IRs in CVC
      and HD cohorts, respectively, were thrombosis, 1.3 and 0.8; MCRCs, 0.6 and 0.7;
      embolism, 0.4 and 0.5; MB, 0.1 and 0.3; and ICH, 0.1 in both cohorts. Patients
      with cancer at baseline had significantly higher IRs for CRBSIs and thrombosis
      than non-cancer patients. CVC or HD catheter-related complications were most
      frequently seen in patients 16 years or younger. CONCLUSIONS: The risk of
      catheter-related complications is highest during the first 90 days of catheter
      placement in patients with CVCs and HD catheters and in younger patients (<=16
      years of age) with HD catheters. Data provided in this study can be applied
      toward improving patient care.

PMID- 24131510
TI  - Harvest: an open platform for developing web-based biomedical data discovery and
      reporting applications.
AB  - Biomedical researchers share a common challenge of making complex data
      understandable and accessible as they seek inherent relationships between
      attributes in disparate data types. Data discovery in this context is limited by
      a lack of query systems that efficiently show relationships between individual
      variables, but without the need to navigate underlying data models. We have
      addressed this need by developing Harvest, an open-source framework of modular
      components, and using it for the rapid development and deployment of custom data
      discovery software applications. Harvest incorporates visualizations of highly
      dimensional data in a web-based interface that promotes rapid exploration and
      export of any type of biomedical information, without exposing researchers to
      underlying data models. We evaluated Harvest with two cases: clinical data from
      pediatric cardiology and demonstration data from the OpenMRS project. Harvest's
      architecture and public open-source code offer a set of rapid application
      development tools to build data discovery applications for domain-specific
      biomedical data repositories. All resources, including the OpenMRS demonstration,
      can be found at http://harvest.research.chop.edu. 

PMID- 24131512
TI  - Diversity of acoustic tracheal system and its role for directional hearing in
      crickets.
AB  - BACKGROUND: Sound localization in small insects can be a challenging task due to
      physical constraints in deriving sufficiently large interaural intensity
      differences (IIDs) between both ears. In crickets, sound source localization is
      achieved by a complex type of pressure difference receiver consisting of four
      potential sound inputs. Sound acts on the external side of two tympana but
      additionally reaches the internal tympanal surface via two external sound
      entrances. Conduction of internal sound is realized by the anatomical arrangement
      of connecting trachea. A key structure is a trachea coupling both ears which is
      characterized by an enlarged part in its midline (i.e., the acoustic vesicle)
      accompanied with a thin membrane (septum). This facilitates directional
      sensitivity despite an unfavorable relationship between wavelength of sound and
      body size. Here we studied the morphological differences of the acoustic tracheal
      system in 40 cricket species (Gryllidae, Mogoplistidae) and species of outgroup
      taxa (Gryllotalpidae, Rhaphidophoridae, Gryllacrididae) of the suborder Ensifera
      comprising hearing and non hearing species. RESULTS: We found a surprisingly high
      variation of acoustic tracheal systems and almost all investigated species using
      intraspecific acoustic communication were characterized by an acoustic vesicle
      associated with a medial septum. The relative size of the acoustic vesicle - a
      structure most crucial for deriving high IIDs - implies an important role for
      sound localization. Most remarkable in this respect was the size difference of
      the acoustic vesicle between species; those with a more unfavorable ratio of body
      size to sound wavelength tend to exhibit a larger acoustic vesicle. On the other
      hand, secondary loss of acoustic signaling was nearly exclusively associated with
      the absence of both acoustic vesicle and septum. CONCLUSION: The high diversity
      of acoustic tracheal morphology observed between species might reflect different
      steps in the evolution of the pressure difference receiver; with a precursor
      structure already present in ancestral non-hearing species. In addition,
      morphological transitions of the acoustic vesicle suggest a possible adaptive
      role for the generation of binaural directional cues.

PMID- 24131513
TI  - Prevalence and clinical predictors of drug-resistant tuberculosis in three
      clinical settings in Calabar, Nigeria.
AB  - BACKGROUND AND AIMS: Drug-resistant tuberculosis (TB) poses a serious challenge
      to global control of TB. This multicentre study was to identify risk factors for
      drug resistance to the first line anti-TB drugs among TB patients presenting for
      care in three health facilities in Calabar, Nigeria. MATERIALS AND METHODS: A
      cohort of 100 consecutive TB patients were recruited. Demographic information
      such as age, sex, weight, height, occupation, previous TB diagnosis and
      treatment, smoking, alcohol dependence and substance abuse were obtained. Sputum
      samples were collected from participants and cultured on Lowenstein - Jensen (LJ)
      slopes. Drug susceptibility testing was then carried out for the isolates
      identified as Mycobacterium tuberculosis, using isoniazid, rifampicin, ethambutol
      and streptomycin. RESULTS: Forty-two of the 100 participants evaluated were found
      to be resistant to at least one drug. Multi-drug-resistant TB was seen in four
      persons. Statistically significant differences were found with respect to three
      variables: younger age, abandonment of TB treatment and presence of cavitary
      lesions on chest radiograph. The variables sex, alcohol dependence, tobacco use
      and previous imprisonment were not significantly associated with TB drug
      resistance. Four variables were significant following the multivariate analysis
      with the following adjusted odds ratios: abandonment of TB treatment (9.34),
      cavitary lesions on chest radiograph (5.88), younger age (6.25) and male sex
      (3.25). CONCLUSION: Thus, risk stratification of TB patients is advocated in
      clinical settings where diagnostic facilities for drug-resistant TB are scarce
      using the identified predictors. This group will benefit from close monitoring
      and early drug susceptibility testing.

PMID- 24131511
TI  - Multimodal neuroimaging of frontal white matter microstructure in early phase
      schizophrenia: the impact of early adolescent cannabis use.
AB  - BACKGROUND: A disturbance in connectivity between different brain regions, rather
      than abnormalities within the separate regions themselves, could be responsible
      for the clinical symptoms and cognitive dysfunctions observed in schizophrenia.
      White matter, which comprises axons and their myelin sheaths, provides the
      physical foundation for functional connectivity in the brain. Myelin sheaths are
      located around the axons and provide insulation through the lipid membranes of
      oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in
      schizophrenia, based on findings of abnormal myelin maintenance and repair in
      regions of deep white matter. The aim of this in vivo neuroimaging project is to
      assess the impact of early adolescent onset of regular cannabis use on brain
      white matter tissue integrity, and to differentiate this impact from the white
      matter abnormalities associated with schizophrenia. The ultimate goal is to
      determine the liability of early adolescent use of cannabis on brain white
      matter, in a vulnerable brain. METHODS/DESIGN: Young adults with schizophrenia at
      the early stage of the illness (less than 5 years since diagnosis) will be the
      focus of this project. Four magnetic resonance imaging measurements will be used
      to assess different cellular aspects of white matter: a) diffusion tensor
      imaging, b) localized proton magnetic resonance spectroscopy with a focus on the
      neurochemical N-acetylaspartate, c) the transverse relaxation time constants of
      regional tissue water, d) and of N-acetylaspartate. These four neuroimaging
      indices will be assessed within the same brain region of interest, that is, a
      large white matter fibre bundle located in the frontal region, the left superior
      longitudinal fasciculus. DISCUSSION: We will expand our knowledge regarding
      current theoretical models of schizophrenia with a more comprehensive multimodal
      neuroimaging approach to studying the underlying cellular abnormalities of white
      matter, while taking into consideration the important confounding variable of
      early adolescent onset of regular cannabis use.

PMID- 24131514
TI  - Isokinetic muscle performance of the hip and ankle muscles in women with
      fibromyalgia.
AB  - OBJECTIVE: To compare isokinetic muscle performances of a proximal (hip) and a
      distal (ankle) muscle of fibromyalgia syndrome (FMS) patients with those of age-
      and body mass index (BMI)-matched healthy subjects. METHODS: Thirty female
      patients with FMS (mean age: 41.5 +/- 6.7 years [range, 27-54]) and 30 age- (mean
      age: 40.6 +/- 6.0 years [range, 27-54]) and BMI-matched female healthy controls
      were consecutively enrolled. Demographic and clinical characteristics of the
      subjects were recorded. Isokinetic measurements of hip and ankle flexion and
      extension at angular velocities of 60 degrees /s and 180 degrees /s, peak
      torques, flexor-extensor torque ratios, muscle fatigue resistance values and
      average power were obtained. RESULTS: Mean disease duration of FMS patients was
      2.4 +/- 1.9 years. Mean weight, height and BMI values were 70.4 +/- 12.5 kg,
      159.5 +/- 6.0 cm and 27.7 +/- 4.7 kg/m2 (FMS patients) and 69.3 +/- 10.1 kg,
      161.7 +/- 6.2 cm and 26.6 +/- 4.3 kg/m2 (control subjects), respectively (all P >
      0.05). All isokinetic values were statistically decreased in the FMS group when
      compared with the control group, except for the peak torques at angular velocity
      of 180 degrees /s on flexion of the hip and extension of the ankle and the total
      work and average power on extension of the ankle. We did not find any correlation
      between isokinetic values and disease related parameters of FMS patients.
      CONCLUSIONS: In the light of our results, we may conclude that muscle strength
      and muscle fatigue seem to decrease in FMS patients' both proximal and distal
      lower extremity muscles.

PMID- 24131515
TI  - A fast regularized least-squares method for retinal vascular oxygen tension
      estimation using a phosphorescence lifetime imaging model.
AB  - BACKGROUND: Monitoring retinal oxygenation is of primary importance in detecting
      the presence of some common eye diseases. To improve the estimation of oxygen
      tension in retinal vessels, regularized least-squares (RLS) method was shown to
      be very effective compared with the conventional least-squares (LS) estimation.
      In this study, we propose an accelerated RLS estimation method for the problem of
      assessing the oxygenation of retinal vessels from phosphorescence lifetime
      images. METHODS: In the previous work, gradient descent algorithms were used to
      find the minimum of the RLS cost function. This approach is computationally
      expensive, especially when the oxygen tension map is large. In this study, using
      a closed-form solution of the RLS estimation and some inherent properties of the
      problem at hand, the RLS process is reduced to the weighted averaging of the LS
      estimates. This decreases the computational complexity of the RLS estimation
      considerably without sacrificing its performance. RESULTS: Performance analyses
      are conducted using both real and simulated data sets. In terms of computational
      complexity, the proposed RLS estimation method is significantly better than RLS
      methods that use gradient descent algorithms to find the minimum of the cost
      function. Additionally, there is no significant difference between the estimates
      acquired by the proposed and conventional RLS estimation methods. CONCLUSION: The
      proposed RLS estimation method for computing the retinal oxygen tension is
      computationally efficient, and produces estimates with negligible difference from
      those obtained by iterative RLS methods. Further, the results of this study can
      be applied to other lifetime imaging problems that have similar properties.

PMID- 24131516
TI  - Vancomycin-modified mesoporous silica nanoparticles for selective recognition and
      killing of pathogenic gram-positive bacteria over macrophage-like cells.
AB  - Rapid, reliable recognition and detection of bacteria from an authentic specimen
      have been gained increasing interests in the past decades. Various materials have
      been designed and prepared for implementation of bacterial recognition and
      treatment in the artificial systems. However, in the complicated physiological
      condition, the macrophages always compromise the outcomes of bacterial detection
      and/or treatment. In this work, we demonstrated the vancomycin-modified
      mesoporous silica nanoparticles (MSNs is a subset of Van) for efficiently
      targeting and killing gram-positive bacteria over macrophage-like cells. Owing to
      the specific hydrogen bonding interactions of vancomycin toward the terminal d
      alanyl-d-alanine moieties of gram-positive bacteria, the MSNs is a subset of Van
      exhibited enhanced recognition for gram-positive bacteria due to the multivalent
      hydrogen binding effect. Furthermore, the fluorescent molecules (FITC) were
      covalently decorated inside of mesopores of MSNs for tracking and visualizing the
      MSNs is a subset of Van during the detection/treatment processes. Upon incubation
      of FITC decorated MSNs with bacteria (i.e., S. aureus and E. coli as gram
      positive and gram-negative bacteria, respectively) or macrophage-like cells (Raw
      264.7), the fluorescence signals in S. aureus were 2-4 times higher than that in
      E. coli and no detectable fluorescence signals were observed in Raw 264.7 cells
      under the same condition. Finally, the MSNs is a subset of Van showed unambiguous
      antibacterial efficacy without decrease in cell viability of macrophage-like
      cells. This new strategy opens a new door for specific detection and treatment of
      pathogenic bacteria with minimized side effects.

PMID- 24131517
TI  - Neurosensory development and cell fate determination in the human cochlea.
AB  - BACKGROUND: Hearing depends on correct functioning of the cochlear hair cells,
      and their innervation by spiral ganglion neurons. Most of the insight into the
      embryological and molecular development of this sensory system has been derived
      from animal studies. In contrast, little is known about the molecular expression
      patterns and dynamics of signaling molecules during normal fetal development of
      the human cochlea. In this study, we investigated the onset of hair cell
      differentiation and innervation in the human fetal cochlea at various stages of
      development. RESULTS: At 10 weeks of gestation, we observed a prosensory domain
      expressing SOX2 and SOX9/SOX10 within the cochlear duct epithelium. In this
      domain, hair cell differentiation was consistently present from 12 weeks,
      coinciding with downregulation of SOX9/SOX10, to be followed several weeks later
      by downregulation of SOX2. Outgrowing neurites from spiral ganglion neurons were
      found penetrating into the cochlear duct epithelium prior to hair cell
      differentiation, and directly targeted the hair cells as they developed.
      Ubiquitous Peripherin expression by spiral ganglion neurons gradually diminished
      and became restricted to the type II spiral ganglion neurons by 18 weeks. At 20
      weeks, when the onset of human hearing is thought to take place, the expression
      profiles in hair cells and spiral ganglion neurons matched the expression
      patterns of the adult mammalian cochleae. CONCLUSIONS: Our study provides new
      insights into the fetal development of the human cochlea, contributing to our
      understanding of deafness and to the development of new therapeutic strategies to
      restore hearing.

PMID- 24131518
TI  - Oral mucosal injury in oncology patients: perspectives on maturation of a field.
AB  - In the past decade, there have been important strategic advances relative to
      pathobiological modeling as well as clinical management for oral mucositis caused
      by cancer therapies. Prior to the 1990s, research in this field was conducted by
      a relatively small number of basic and clinical investigators. Increasing
      interest among researchers and clinicians over the past twenty years has produced
      a synergistic outcome characterized by a number of key dynamics, including novel
      discovery models for pathobiology, increased experience in designing and
      conducting clinical trials, and creation of international collaborations among
      cancer care professionals who in turn have modeled clinical care paradigms based
      on state-of-the-science evidence. This maturation of the science and its clinical
      translation has positioned investigators and oncology providers to further
      accelerate both the foundational research and the clinical modeling for patient
      management in the years ahead. The stage is now set to further capitalize upon
      optimizing the interactions across this interface, with the goal of strategically
      enhancing management of patients with cancer at risk for this toxicity while
      reducing the cost of cancer care. 

PMID- 24131519
TI  - Automatically transforming pre- to post-composed phenotypes: EQ-lising HPO and
      MP.
AB  - BACKGROUND: Large-scale mutagenesis projects are ongoing to improve our
      understanding about the pathology and subsequently the treatment of diseases.
      Such projects do not only record the genotype but also report phenotype
      descriptions of the genetically modified organisms under investigation. Thus far,
      phenotype data is stored in species-specific databases that lack coherence and
      interoperability in their phenotype representations. One suggestion to overcome
      the lack of integration are Entity-Quality (EQ) statements. However, a reliable
      automated transformation of the phenotype annotations from the databases into EQ
      statements is still missing. RESULTS: Here, we report on our ongoing efforts to
      develop a method (called EQ-liser) for the automated generation of EQ
      representations from phenotype ontology concept labels. We implemented the
      suggested method in a prototype and applied it to a subset of Mammalian and Human
      Phenotype Ontology concepts. In the case of MP, we were able to identify the
      correct EQ representation in over 52% of structure and process phenotypes.
      However, applying the EQ-liser prototype to the Human Phenotype Ontology yields a
      correct EQ representation in only 13.3% of the investigated cases. CONCLUSIONS:
      With the application of the prototype to two phenotype ontologies, we were able
      to identify common patterns of mistakes when generating the EQ representation.
      Correcting these mistakes will pave the way to a species-independent solution to
      automatically derive EQ representations from phenotype ontology concept labels.
      Furthermore, we were able to identify inconsistencies in the existing manually
      defined EQ representations of current phenotype ontologies. Correcting these
      inconsistencies will improve the quality of the manually defined EQ statements.

PMID- 24131520
TI  - The geographical patterns of symbiont diversity in the invasive legume Mimosa
      pudica can be explained by the competitiveness of its symbionts and by the host
      genotype.
AB  - Variations in the patterns of diversity of symbionts have been described
      worldwide on Mimosa pudica, a pan-tropical invasive species that interacts with
      both alpha and beta-rhizobia. In this study, we investigated if symbiont
      competitiveness can explain these variations and the apparent prevalence of beta-
      over alpha-rhizobia. We developed an indirect method to measure the proportion of
      nodulation against a GFP reference strain and tested its reproducibility and
      efficiency. We estimated the competitiveness of 54 strains belonging to four
      species of beta-rhizobia and four of alpha-rhizobia, and the influence of the
      host genotype on their competitiveness. Our results were compared with
      biogeographical patterns of symbionts and host varieties. We found: (i) a strong
      strain effect on competitiveness largely explained by the rhizobial species, with
      Burkholderia phymatum being the most competitive species, followed by B. tuberum,
      whereas all other species shared similar and reduced levels of competitiveness;
      (ii) plant genotype can increase the competitiveness of Cupriavidus taiwanensis.
      The latter data support the likelihood of the strong adaptation of C. taiwanensis
      with the M. pudica var. unijuga and help explain its prevalence as a symbiont of
      this variety over Burkholderia species in some environments, most notably in
      Taiwan. 

PMID- 24131521
TI  - Distribution and genetic diversity of Southern rice black-streaked dwarf virus in
      China.
AB  - BACKGROUND: Rice and maize dwarf diseases caused by the newly introduced Southern
      rice black-streaked dwarf virus (SRBSDV) have led to severe economic losses in
      South China in recent years. The distribution and diversity of SRBSDV have not
      been investigated in the main rice and maize growing areas in China. In this
      study, the distribution of SRBSDV in China was determined by using reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Between 2009 and 2010,
      2404 plant samples (2294 rice, 110 maize samples, and more than 300 cultivars)
      with dwarf symptoms were collected from fields in 194 counties of 17 provinces in
      China and SRBSDV was detected. The results indicated that 1545 (64.27%) of
      samples (both rice and maize) were infected with SRBSDV. SRBSDV was detected
      widely in Hainan, Guangdong, Guangxi, Yunnan, Guizhou, Chongqing, Fujian,
      Jiangxi, Hunan, Hubei, Anhui, Jiangsu, and Zhejiang provinces, which suggests
      SRBSDV is an important pathogen causing rice dwarfing diseases in South China.
      Phylogenetic analysis of 15 representative virus isolates revealed that SRBSDV
      isolates in China had high levels of nucleotide and amino acid sequence
      identities (>97.8%). CONCLUSIONS: SRBSDV spreads naturally in Yangtze River basin
      and south region, the location of the major rice production areas. In comparison,
      the virus rarely spreads north of Yangtze River in North China. Distribution of
      SRBSDV is consistent with the migrating and existing ranges of its vector WBPH,
      suggesting that SRBSDV might be introduced into South China along with the
      migration of viruliferous WBPH.

PMID- 24131522
TI  - Facial skin and soft tissue infection caused by Mycobacterium wolinskyi
      associated with cosmetic procedures.
AB  - BACKGROUND: Mycobacteirum wolinskyi is a member of the Mycobacterium smegmatis
      group, which is less frequently found in clinical settings than other
      nontuberculous mycobacterium (NTM) species. However, its clinical significance
      has recently increased in opportunistic infections. This case is the first report
      of facial skin and soft tissue infection by M. wolinskyi complicating cosmetic
      procedures. CASE PRESENTATION: A 56-year-old Asian female patient with a history
      of receiving multiple facial cosmetic procedures over the preceding 2 years was
      admitted to our institution with swelling, local pain, and erythema on the right
      cheek. Mycobacteirum fortuitum complex isolated from a pus culture was identified
      as M. wolinskyi by rpoB sequencing. Metallic foreign bodies and abscess were
      detected by radiologic imaging. The pus was incised and drained. Treatment
      comprised clarithromycin (500 mg every 12 h), amikacin (200 mg every 8 h), and
      ciprofloxacin (400 mg every 6 h). CONCLUSION: We report the first case of facial
      skin and soft tissue infection with M. wolinskyi after multiple cosmetic
      procedures of filler injection and laser lipolysis. Increased occurrence of NTM
      infection in nosocomial settings suggests the importance of appropriate treatment
      including culturing and rpoB gene sequencing when patients who have undergone
      cosmetic procedures display symptoms and signs of soft tissue infection
      indicative of NTM infection.

PMID- 24131523
TI  - MTHFR 677TT genotype and disease risk: is there a modulating role for B-vitamins?
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising
      enzyme which requires riboflavin as its co-factor. A common polymorphism (677C
      >T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn
      leads to impaired folate metabolism and elevated homocysteine concentrations.
      Homozygosity for this polymorphism (TT genotype) is associated with an increased
      risk of a number of conditions including heart disease and stroke, but there is
      considerable variability in the extent of excess risk in various reports. The
      present review will explore the evidence which supports a role for this
      polymorphism as a risk factor for a number of adverse health outcomes, and the
      potential modulating roles for B-vitamins in alleviating disease risk. The
      evidence is convincing in the case which links this polymorphism with
      hypertension and hypertensive disorders of pregnancy, particularly preeclampsia.
      Furthermore, elevated blood pressure was found to be highly responsive to
      riboflavin intervention specifically in individuals with the MTHFR 677TT
      genotype. Future intervention studies targeted at these genetically predisposed
      individuals are required to further investigate this novel gene-nutrient
      interaction. This polymorphism has also been associated with an increased risk of
      neural tube defects (NTD) and other adverse pregnancy outcomes; however, the
      evidence in this area has been inconsistent. Preliminary evidence has suggested
      that there may be a much greater need for women with the MTHFR 677TT genotype to
      adhere to the specific recommendation of commencing folic acid prior to
      conception for the prevention of NTD, but this requires further investigation. 

PMID- 24131524
TI  - Patient-initiated questions: How can doctors encourage them and improve the
      consultation process? A qualitative study.
AB  - OBJECTIVE: To investigate the circumstances under which patients initiate direct
      questions in oncology consultations. DESIGN: Conversation analysis of 47
      consultations between oncologists and patients with cancer. SETTING: An oncology
      clinic at a teaching hospital in the East Midlands. PARTICIPANTS: 16 Oncologists
      and 67 cancer patients. OUTCOME MEASURE: Patient initiated direct questions.
      RESULTS: On the whole patients' direct questions are designed to seek specific
      information regarding, the cancer itself, treatment options or their experience
      of symptoms. When patients do ask direct questions they typically follow the
      announcement of test results where some reference to the details of those
      results, is provided. More specifically, there seems to be a relation between
      showing the patient their scan/X-ray results, patient involvement and patient
      initiated direct questions. Higher levels of patient-initiated direct questions
      were clustered around occasions where doctors provided information and
      explanations of test results (12 consultations) sometimes with direct reference
      to scan or X-ray results (7 consultations). CONCLUSIONS: This study highlights
      the importance of careful explanation of diagnostic evidence as a factor
      contributing to increased patient involvement. More specifically, the findings
      suggest that, when appropriate, invoking diagnostic evidence (eg, scan or X-ray
      results) is an effective way of increasing levels of patient question asking.
      Doctors need to be able to encourage patient question asking to ensure that
      patients have at their disposal an important means through which they can
      determine their information needs. Although these results come from a study of
      oncology consultations, the findings may be transferable to other clinical
      contexts.

PMID- 24131525
TI  - Prevalence and incidence rates of autism in the UK: time trend from 2004-2010 in
      children aged 8 years.
AB  - OBJECTIVES: To update UK studies begun in the early 1990s on the annual
      prevalence and incidence rates of autism in children; undertaken in response to a
      March 2012 press release, widely covered by the media, from the US Centre for
      Disease Control (CDC) reporting that the autism prevalence rate in 2008 in 8-year
      old US children was 1 in 88, a 78% increase from a CDC estimate in 2004. This
      finding suggested a continuation of the dramatic increase in children diagnosed
      as autistic, which occurred in the 1990s. DESIGN: Population study using the UK
      General Practice Research Database (GPRD). METHODS: Annual autism prevalence
      rates were estimated for children aged 8 years in 2004-2010 by dividing the
      number diagnosed as autistic in each or any previous year by the number of
      children active in the study population that year. We also calculated annual
      incidence rates for children aged 2-8 years, by dividing the number newly
      diagnosed in 2004-2010 by the same denominators. RESULTS: Annual prevalence rates
      for each year were steady at approximately 3.8/1000 boys and 0.8/1000 girls.
      Annual incidence rates each year were also steady at about 1.2/1000 boys and
      0.2/1000 girls. CONCLUSIONS: Following a fivefold increase in the annual
      incidence rates of autism during the 1990s in the UK, the incidence and
      prevalence rates in 8-year-old children reached a plateau in the early 2000s and
      remained steady through 2010. Whether prevalence rates have increased from the
      early 2000s in the USA remains uncertain.

PMID- 24131526
TI  - Spirometry may underestimate airway obstruction in professional Greek athletes.
AB  - PURPOSE: Lung development and consequently, lung volumes, are affected by the
      duration, type and intensity of sporting. Athletes may have higher spirometric
      values compared to predicted which may lead to misclassification of this
      population and misdiagnosis during clinical evaluation. The aim of the study was
      to compare measured spirometric values with those predicted from the European
      Community for Steel and Coal statement in Greek professional athletes. METHODS:
      Measured and predicted spirometric values were recorded from 276 normal
      professional athletes (168 males, 108 females), aged 15-60 years originated from
      the metropolitan area of Athens, Greece. Predicted and measured spirometric
      values were compared using a paired sample t-test and analysed using Bland-Altman
      method. RESULTS: Measured FEV1 was 109.6 (1.02%) and 109.4 (1.29%) and FVC was
      110.8 (1.07%) and 109.6 (1.02%) compared to predicted in males and females
      respectively. The FEV1 /FVC ratio was 102.2 (0.55%) and 103.2 (0.58%) compared to
      predicted for males and females, respectively. Bland-Altman analysis revealed a
      significant bias and magnitude of difference between predicted and measured
      spirometric values. CONCLUSIONS: European Community for Steel and Coal predicted
      spirometric values significantly underestimated measured lung volumes and FEV1
      /FVC ratio in Greek athletes of both sexes. Predicted spirometric indices should
      be used with caution in the evaluation of athletes presenting with respiratory
      symptoms for the risk of underestimation of restrictive disease or airway
      obstruction.

PMID- 24131527
TI  - A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with
      cirrhosis in hepatitis C virus carriers.
AB  - BACKGROUND & AIMS: Host genetic factors could play a primary role in determining
      risk for cirrhosis development in HCV-infected patients. The aims of this study
      were to discover new genetic variants associated with this trait and to replicate
      some associations formerly reported. METHODS: Three hundred and thirty-seven HCV
      carriers with available data about liver fibrosis status, who initiated treatment
      with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%)
      were cirrhotic. One hundred and forty-four SNPs from 40 genes related to
      cholesterol metabolism/transport, sustained viral response to HCV therapy, liver
      fibrosis, or immune response, were genotyped in all samples. Plink software was
      used to perform univariate association analyses. The results obtained were
      adjusted by other parameters related to cirrhosis using multivariate logistic
      regression models. RESULTS: Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3
      and BCL2L12 genes, was associated with cirrhosis. It was observed a higher
      proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%)
      than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P
      = 0.006). This effect was stronger in the background of rs12979860 CC genotype of
      IL28B (adjusted OR = 0.069, 95% CI = 0.014-0.349, P = 0.001). CONCLUSION: The
      rs12104272 SNP could have clinical value to select those individuals at lower
      risk for cirrhosis development.

PMID- 24131528
TI  - Online cognitive behaviour training for the prevention of postnatal depression in
      at-risk mothers: a randomised controlled trial protocol.
AB  - BACKGROUND: Postnatal depression (PND) is the most common disorder of the
      puerperium with serious consequences for both mother and child if left untreated.
      While there are effective treatments, there are many barriers for new mothers
      needing to access them. Prevention strategies may offer a more acceptable means
      of addressing the problem. Internet interventions can help overcome some barriers
      to reducing the impact of PND. However, to date there are no published studies
      that investigate the efficacy of internet interventions for the prevention of
      PND. METHODS/DESIGN: The proposed study is a two-arm double blind randomised
      controlled trial. 175 participants will be recruited in the immediate postnatal
      period at an Australian community hospital. Women who meet inclusion criteria
      (internet access, email address, telephone number, over 18, live birth, fluent
      English) will complete the Edinburgh Postnatal Depression Scale (EPDS). Those
      with a score above 9 will undertake the Structured Clinical Interview for DSM
      Disorders (SCID). Those with a clinical diagnosis of depression, or a lifetime
      diagnosis of bipolar disorder or psychosis on the SCID will be excluded.
      Following completion of the baseline battery women will be randomised using a
      computer-generated algorithm to either the intervention or control condition. The
      intervention will consist of 5 modules of automated, interactive cognitive
      behaviour training (CB training), completed weekly with email reminders. The
      control will replicate the level of contact participants experience with the
      intervention, but the content will be of a general health nature. Participants
      will complete questionnaires immediately post-intervention (6 weeks) and 3-, 6-
      and 12 months follow-up. There will also be a second SCID delivered via telephone
      at 6 months. We hypothesise that relative to the control group, the intervention
      group will show a greater reduction in postnatal distress on the EPDS (primary
      outcome measure). We also hypothesise that the intervention group will
      demonstrate lower levels of anxiety and stress and higher levels of parenting
      confidence than the control group following intervention and/or follow-up.
      DISCUSSION: The proposed study addresses a number of limitations of earlier
      trials. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registers,
      ACTRN12609001032246.

PMID- 24131529
TI  - Simultaneous quantification of myocardial and blood flow velocities based on
      duplex mode ultrasound imaging.
AB  - BACKGROUND: Ultrasound imaging of the heart is a commonly used clinical tool to
      assess cardiac function. The basis for this analysis is the quantification of
      cardiac blood flow and myocardial velocities. These are typically measured using
      different imaging modes and on different cardiac cycles. However, due to beat-to
      beat variations such as irregular heart rhythm and transient events, simultaneous
      acquisition is preferred. There exists specialized ultrasound systems for this
      purpose; however, it would be beneficial if this could be achieved using
      conventional ultrasound systems due to their wide availability. The conventional
      Duplex mode ultrasound allows simultaneous acquisition, however at a highly
      reduced spatial and temporal resolution. METHODS: The aim of this work was to
      present and evaluate the performance of a novel method to recover myocardial
      tissue velocity using conventional Duplex ultrasound imaging, and to demonstrate
      its feasibility for the assessment of simultaneous blood flow and myocardial
      velocity in-vivo. The essence of the method was the estimation of the axial phase
      shift of robust echogenic structures between subsequent image frames. The
      performance of the method was evaluated on synthetic tissue mimicking B-mode
      image sequences at different frame rates (20-60 Hz) and tissue velocities (peak
      velocities 5-15cm/s), using cardiac deformation and displacement characteristics.
      The performance was also compared to a standard 2-D speckle tracking technique.
      RESULTS: The method had an overall high performance at frame rates above 25 Hz,
      with less than 15% error of the peak diastolic velocity, and less than 10 ms peak
      timing error. The method showed superior performance compared to the 2-D tracking
      technique at frame rates below 50 Hz. The in-vivo quantification of simultaneous
      blood flow and myocardial tissue velocities verified the echocardiographic
      patterns and features of healthy subjects and the specific patient group.
      CONCLUSIONS: A novel myocardial velocity quantification method was presented and
      high performance at frame rates above 25 Hz was shown. In-vivo quantification of
      simultaneous myocardial and blood flow velocities was feasible using the proposed
      method and conventional Duplex mode imaging. We propose that the methodology is
      suitable for retrospective as well as prospective studies on the mechanics and
      hemodynamics of the heart.

PMID- 24131531
TI  - The role of reporting standards for metabolite annotation and identification in
      metabolomic studies.
AB  - The application of reporting standards in metabolomics allow data from different
      laboratories to be shared, integrated and interpreted. Although minimum reporting
      standards related to metabolite identification were published in 2007, it is
      clear that significant efforts are required to ensure their continuous update and
      appropriate use by the metabolomics community. These include their use in
      metabolomics data submission (e.g., MetaboLights) and as a requirement for
      publication in peer-reviewed journals (e.g., Metabolomics). The Data Standards
      and Metabolite Identification Task Groups of the international Metabolomics
      Society are actively working to develop and promote these standards and educate
      the community on their use. 

PMID- 24131530
TI  - The expanding spectrum of rare monogenic autoinflammatory diseases.
AB  - Monogenic autoinflammatory diseases are a group of hereditary disorders
      characterized by a clinical and biological inflammatory syndrome in which there
      is little or no evidence of autoimmunity. The discovery of the first causative
      gene in 1997 was rapidly followed by the identification of many others from the
      same group. The mutated proteins can be directly or indirectly involved in the
      regulation of inflammation. The available literature includes numerous reviews,
      which address the principle diseases, but we wanted to focus on the most recent
      rare syndromes. A comprehensive review is thus provided, including taxonomic,
      genetic, and epidemiological data, along with characteristics defining positive
      and differential diagnoses and treatment. We believe that this update will assist
      physicians in correctly naming their patient's illness. This is an essential step
      for the effective and targeted management of an orphan disease. 

PMID- 24131532
TI  - Perceived decisional responsibility for mechanical ventilation and weaning: a
      Norwegian survey.
AB  - AIM: To explore variability in perceptions of nurse managers and physician
      directors regarding roles, responsibilities and clinical-decision making related
      to mechanical ventilator weaning in Norwegian intensive care units (ICUs).
      BACKGROUND: Effective teamwork is crucial for providing optimal patient care in
      ICU. More knowledge on nurses' and physicians' perceptions of responsibility in
      clinical decision-making for mechanical ventilation is needed. METHODS: Self
      administered survey of mechanical ventilation and weaning responsibilities was
      sent to nurse managers and physician directors of Norwegian adult ICUs. Nurses'
      decisional influence and autonomy were estimated on a numeric rating scale (NRS)
      from 0 to 10 (least to most). RESULTS: Response rate was 38/60 (63%) nurses and
      38/52 (73%) physicians. On the NRS nurse managers perceived the autonomy and
      influence of nurses' ventilator decisions higher than physician directors: median
      of 7 (IQR 5-8) (nurses) versus 5 (3-6) (physicians), (p < 0.01), and 8 (7-9)
      (nurses) versus 7 (5-8) (physicians), (p < 0.01) respectively. Respondents agreed
      that nurses collaborated in assessment of patient response to ventilator changes
      and titrating ventilator settings: 92% of nurses and 87% of physicians, (p =
      0.46), and recognizing weaning failure 84% of nurses and 84% of physicians, (p =
      0.96). Physician directors perceived significantly less collaborative decision
      making on weaning method (p = 0.01), weaning readiness (p = 0.04) and readiness
      to extubate (p < 0.01) than nurse managers. Both groups acknowledged the
      importance of 'knowing the patient' for weaning success, and agreed that the
      assessment of work of breathing, well-being, and clinical deterioration were
      important for determining weaning tolerance. CONCLUSIONS: Nurse managers
      perceived nurses to have greater autonomy, influence and collaborative
      interaction regarding decisions on mechanical ventilation than physician
      directors. Greater awareness and acknowledgment of nurses' role may promote
      interprofessional collaboration and improve patient care.

PMID- 24131533
TI  - Combined measurement of multiple acute phase reactants to predict relapse of
      rheumatoid arthritis.
AB  - AIM: Acute phase reactants (APRs), such as serum C-reactive protein (CRP),
      ferritin, plasma fibrinogen and platelet count, are common biomarkers used to
      monitor the status of inflammatory diseases. The aim of this study was to
      determine whether APRs are predictive markers of relapse in rheumatoid arthritis
      (RA). METHOD: We analyzed forty RA patients in clinical remission (disease
      activity score [DAS28] < 2.6; baseline [t(0)]) or with low disease activity
      (DAS28 score <= 3.2; t(0)). The pre-existing therapeutic regimens were retained
      for each patient during a 4-week study period. APRs and patient characteristics
      were analyzed for normality of distribution by using the Kolmogorov-Smirnov test
      and correlations were assessed by Pearson's or Spearman's rank correlation
      coefficient. RESULTS: APR levels were found to be significantly correlated with
      DAS28 score of RA, and serum CRP was the most strongly correlated APR for both
      the clinical remission and high disease activity groups. For all APRs, the
      correlation strength paralleled the increase in disease activity. CONCLUSION:
      Measurement of multiple APRs in remission or low disease activity RA patients may
      predict relapse to active disease, thereby facilitating more timely clinical
      management and promoting efficacy of therapeutic intervention.

PMID- 24131534
TI  - Superhydrophobic surfaces from hierarchically structured wrinkled polymers.
AB  - This work reports the creation of superhydrophobic wrinkled surfaces with
      hierarchical structures at both the nanoscale and microscale. A nanoscale
      structure with 500 nm line gratings was first fabricated on poly(hydroxyethyl
      methacrylate) films by nanoimprint lithography while a secondary micro-scale
      structure was created by spontaneous wrinkling. Compared with random wrinkles
      whose patterns show no specific orientation, the hierarchical wrinkles exhibit
      interesting orientation due to confinement effects of pre-imprinted line
      patterns. The hierarchically wrinkled surfaces have significantly higher water
      contact angles than random wrinkled surfaces, exhibiting superhydrophobicity with
      water contact angles higher than 160 degrees  and water sliding angle lower than
      5 degrees . The hierarchically structured wrinkled surfaces exhibit tunable
      wettability from hydrophobic to superhydrophobic and there is an observed
      transition from anisotropic to isotropic wetting behavior achievable by adjusting
      the initial film thickness. 

PMID- 24131539
TI  - The role of carnitine on ovariectomy and inflammation-induced osteoporosis in
      rats.
AB  - This study was carried out to assess the protective bone-sparing effect of
      carnitine with anti-inflammatory properties on chronic inflammation-induced bone
      loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight
      groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised
      (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy +
      inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8)
      OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and
      8) were allowed to recover for two months. Sixty days after the OVX, inflammation
      was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5
      and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the
      60th to the 80th day. Serum levels of TNF-alpha, IL-1, IL-6, OP, and OC were
      assessed to determine inflammation and to evaluate osteoblastic activity. Bone
      mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur
      bones of rats. Carnitine administration was able to restore BMD up to values
      measured in both the OVX and the SH animals. The serum levels of TNF-alpha, IL
      1beta, and IL-6 were increased significantly in the OVXinf rats compared with the
      SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels
      exacerbated this bone loss, as supported by values of BMD of the total femur. The
      two different doses of carnitine reduced bone loss and improved inflammatory
      biomarkers. 

PMID- 24131541
TI  - An early and late cytotoxicity evaluation of lidocaine on human oral mucosa
      fibroblasts.
AB  - Local anesthetic drugs are extensively used in dentistry. However, the cytotoxic
      effects of these pharmaceutical compounds remain unclear. In this work, we have
      evaluated the cell viability and cell function of human oral mucosa fibroblasts
      exposed to different concentrations of lidocaine for increasing incubation times,
      using a global screening methods including structural, metabolic and
      microanalytical analyses. Our results demonstrate that lidocaine is able to alter
      cell viability and function even at low concentrations and times, although the
      effect of lidocaine concentration was more important than the incubation time.
      First, the structural analysis methods revealed that >=5% concentrations of
      lidocaine are able to significantly reduce cell viability. Then, the metabolic 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and water
      soluble tetrazolium salt (WST-1) assays suggest that concentrations starting from
      1% were able to significantly hinder cell physiology. Finally, electron-probe X
      ray microanalysis confirmed the deleterious effects of lidocaine and allowed us
      to demonstrate that these effects are associated to an apoptosis process of cell
      death. Therefore, care should be taken when lidocaine is clinically used, and the
      lowest efficient concentrations should always be used. Furthermore, these results
      suggest that the comprehensive evaluation method used in this work is accurate
      and efficient for screening of local anesthetics. 

PMID- 24131540
TI  - The antiallergic mechanisms of Citrus sunki and bamboo salt (K-ALL) in an
      allergic rhinitis model.
AB  - The antiallergic effects of traditional medicines have long been studied.
      Traditional Korean medicine, Citrus sunki and bamboo salt, has been used for the
      treatment of allergic diseases in Korea. K-ALL, composed of Citrus sunki and
      bamboo salt, is a newly prepared prescription for allergic patients. To develop
      the new antiallergic agent, we examined the effects of K-ALL through in vivo and
      in vitro models. K-ALL and naringin (an active compound of K-ALL) significantly
      inhibited histamine release from rat peritoneal mast cells. This inhibitory
      effect of K-ALL on histamine release was higher than effects from other known
      histamine inhibitors such as bamboo salt, Citrus sunki or disodium cromoglycate.
      K-ALL significantly inhibited systemic anaphylactic shock induced by the compound
      48/80 and passive cutaneous anaphylaxis induced by the IgE. K-ALL also inhibited
      production and mRNA expression of inflammatory cytokines induced by phorbol 12
      myristate 13-acetate and the calcium ionophore A23187 on HMC-1 cells (a human
      mast cell line). In the ovalbumin-induced allergic rhinitis animal model, rub
      scores, histamine, IgE, inflammatory cytokines and inflammatory cell counts were
      all reduced by the oral or nasal administration of K-ALL (pre and posttreatment).
      These results indicate the great potential of K-ALL as an active immune modulator
      for the treatment of mast cell-mediated allergic diseases. 

PMID- 24131542
TI  - Construction of adipose scaffold for bone repair with gene engineering bone
      cells.
AB  - The bone defect repairing is still a challenge in orthopedics. As the gene
      engineering bones have been used in the bone repairing clinic, the scaffold
      construction is a critical fact to be considered. This study aims to construct
      optimal scaffolds using adipose tissue in the bone repair together with the gene
      engineering osteocytes. Rat adipose stem cells (ASC) were prepared; the cells
      were transduced with the OCT-4 gene carrying lentiviral vectors (OCT-4-Lv).
      Artificial bone defects were created in the rat femoral bone. The bone defects
      were filled up with adipose scaffolds and shaped by using surrounding muscles and
      supported with orthopedic splints. ASCs with or without transducing the OCT-4-Lv
      were injected into the adipose scaffolds. The rats were sacrificed 12 weeks after
      the surgery. After receiving the OCT-4-Lv, the expressions of OCT-4, RUNX2 and
      osteocalcin were detected in the ASCs. X-ray examination showed that rats
      received the OCT-4-Lv transduced ASCs together with the adipose pad had new bone
      formation in the defect area; none of the control rats showed any new bone
      formation in situ. The results were supported by histological assessment. Using
      adipose scaffold and OCT-4-modified ASC transplantation can repair bone defects. 

PMID- 24131543
TI  - Pefluorocarbon inhibition of bubble induced Ca2+ transients in an in vitro model
      of vascular gas embolism.
AB  - Endothelial injury resulting from deleterious interaction of gas microbubbles
      occurs in many surgical procedures and other medical interventions. The symptoms
      of vascular air embolism (VAE), while serious, are often difficult to detect, and
      there are essentially no pharmaceutical preventative or post-event treatments
      currently available. Perfluorocarbons (PFCs), however, have shown particular
      promise as a therapeutic option in reducing endothelial injury both in- and ex
      vivo. Recently, we demonstrated the effectiveness of Oxycyte, a third-generation
      PFC formulated in a phosphotidylcholine emulsion, using an in vitro model of VAE
      developed in our laboratory. This apparatus allows live cell imaging concurrent
      with precise manipulation of physiologically sized microbubbles so that they may
      be brought into individual contact with human umbilical vein endothelial cells
      dye-loaded with the Ca(2+) sensitive Fluo-4. Herein, we expand use of this
      fluorescence microscopy-based cell culture model. Specifically, we examined the
      concentration dependence of Oxycyte in reducing both the amplitude and frequency
      of large intracellular Ca(2+) currents that are both a hallmark of bubble contact
      and a quantifiable indication that abnormal intracellular signaling has been
      triggered. We measured dose dependence curves and fit the resultant data using a
      modified Black and Leff operational model of agonism. The half maximal inhibitory
      concentrations of Oxycyte for (i) inhibition of occurrence and (ii) amplitude
      reduction were 229 +/- 49 uM and 226 +/- 167 uM, respectively. This investigation
      shows the preferential gas/liquid interface occupancy of the PFC component of
      Oxycyte over that of mechanosensing glycocalyx components and validates Oxycyte's
      specific surfactant mechanism of action. Further, no lethality was observed for
      any concentration of this bioinert PFC, as it acts as a competitive allosteric
      inhibitor of syndecan activation to ameliorate cell response to bubble contact. 

PMID- 24131544
TI  - Hygiene perception changes during the influenza A H1N1 pandemic in Germany:
      incorporating the results of two cross-sectional telephone surveys 2008-2009.
AB  - BACKGROUND: The federal campaign Wir gegen Viren [Us against viruses] promoted
      hygiene in Germany during the influenza A H1N1 pandemic in 2009. The intervention
      aimed to encourage people to protect themselves against respiratory infections by
      simple means of hygiene behaviour. Quantitative research was carried out to
      outline changes in hygiene perception of the population over time, and to find
      out whether the potential hygiene perception changes were consistent to the
      federal campaign about hygiene or not. METHODS: To determine changes in the
      hygiene perception of the population, two cross-sectional telephone surveys were
      held, each one with n = 2006 participants. The initial survey was carried out
      before the influenza A H1N1 pandemic in calendar week 49-51 in 2008 and the
      second in week 48 in 2009 directly after the peak of the pandemic in Germany. The
      questionnaire contained indicators about perceived hand hygiene efficacy,
      preference for coughing into the sleeve, propensity for presenteeism while
      showing symptoms of a cold and acceptance of hygiene masks. RESULTS: The
      proportion of people who perceive the efficacy of hand washing as "very good"
      increased significantly from 50.9% in 2008 to 61.1% in 2009. The proportion of
      people who perceive coughing into the sleeve as the best way to cough increased
      even more dramatically from 4.8% in 2008 to 38.3% in 2009. In contrast the
      propensity for presenteeism decreased significantly: The proportion of people who
      state that they always report to work while they show symptoms of a cold
      decreased from 50.8% in 2008 to 40.9% in 2009. Acceptance of hygiene masks has
      not changed significantly from 2008 to 2009. CONCLUSIONS: The results revealed
      changes in hygiene perception during influenza A H1N1 pandemic in Germany. The
      changes we found are in accordance with the hygiene recommendations given by the
      federal campaign Wir gegen Viren [Us against viruses]. Results can constitute a
      practical benchmark for future research about hygiene perception and hygiene
      promotion for adults. A pivotal question is: does the increase in hygiene
      perception persist after the pandemic has ceased?

PMID- 24131545
TI  - Severe asymptomatic non-alcoholic fatty liver disease in routine diabetes care; a
      multi-disciplinary team approach to diagnosis and management.
AB  - OBJECTIVES: To prospectively use a non-invasive algorithm to identify
      asymptomatic, advanced non-alcoholic fatty liver disease (NAFLD) in a secondary
      care diabetes clinic and to determine the short-term effect of a multi
      disciplinary team (MDT) approach in a liver clinic. RESEARCH DESIGN AND METHODS:
      NAFLD Fibrosis Score (NFS) was calculated in 64 asymptomatic patients with type 2
      diabetes. Advanced fibrosis was identified using transient elastography and
      confirmed with liver biopsy. In a subsequent retrospective study, 95 patients
      newly referred to the NAFLD MDT clinic were investigated and the impact of the
      MDT approach assessed. RESULTS: 25/64 (39.0%) of patients with diabetes had a low
      NFS (<-1.455). 39/64 (61.0%) patients had a high or indeterminate NFS and were
      referred for review in the NAFLD MDT clinic, of which 23/39 attended for
      assessment. 19/23 (82.6%) were diagnosed with NAFLD, of which 6/19 (31.6%)
      patients had a positive transient elastography (>=8 kPa). Liver biopsy confirmed
      advanced fibrosis in 5/6 cases, with moderate fibrosis in 1 case. In the
      retrospective study, 65/95 (68.4%) new referrals to the NAFLD MDT clinic had a
      diagnosis of NAFLD. Over a median 98 days (IQR 70-182) follow-up, there was a
      significant improvement in weight (-0.8 kg; P = 0.024), total cholesterol (-0.2
      mmol/L; P = 0.044), ALT (alanine transmaminase, -12.5 IU/L; P < 0.001) and GGT
      (gammu-glutamyl transferase, -13.0 IU/L; P < 0.0001). 7/28 (25%) of patients with
      diabetes achieved >5% weight loss. CONCLUSIONS: A significant proportion of
      asymptomatic patients attending type 2 diabetes clinics have undiagnosed advanced
      NAFLD fibrosis. An MDT approach to NAFLD results in short-term improvements in
      metabolic and liver parameters.

PMID- 24131547
TI  - Scimitar syndrome.

PMID- 24131548
TI  - Sherlock Holmes and clinical excellence.

PMID- 24131546
TI  - Plasma exchange induces vitamin D deficiency.
AB  - BACKGROUND: Plasma exchange is used in the treatment of diseases mediated by
      pathogenic circulating proteins, or for transplant desensitization. Its non
      targeted nature results in the depletion of physiologically important molecules,
      and it is often complicated by hypocalcaemia. AIM: To determine the effects of
      plasma exchange on vitamin D binding protein (DBP) and associated vitamin D
      metabolites. DESIGN: Single-centre prospective cohort study of 11 patients.
      METHODS: DBP and vitamin D metabolites were measured before and immediately after
      five plasma exchanges, and 7 and 28 days after discontinuation of plasma
      exchange. RESULTS: Plasma exchange reduced plasma DBP concentration from 196.9 +/
      53.2 to 98.5 +/- 34 MUg/ml (P = 0.0001), 1,25-dihydroxyvitamin D from 103 +/- 52
      to 42 +/- 4 pmol/l (P = 0.003) and 25-hydroxyvitamin D from 49.7 +/- 29 to 22 +/-
      9.4 nmol/l (P = 0.0017), through their removal in effluent. After 7 days, DBP and
      1,25-dihydroxyvitamin D were not significantly different from baseline, but 25
      hydroxyvitamin D remained significantly lower after 7 days (26.4 +/- 9.8 nmol/l,
      P = 0.02) and 28 days (30.8 +/- 15.5 nmol/l, P = 0.048). Corrected calcium
      decreased from 2.23 +/- 0.11 to 1.98 +/- 0.08 mmol/l (P = 0.0007) immediately
      after five treatments. Plasma calcium was significantly associated with 1,25
      dihydroxyvitamin D (r(2) = 0.79, P < 0.0001). CONCLUSION: Plasma exchange induced
      an acute reversible decrease in plasma 1,25-dihydroxyvitamin D, DBP, calcium and
      a sustained decrease in plasma 25-hydroxyvitamin D.

PMID- 24131549
TI  - Prognostic impact of systemic inflammatory diseases in elderly patients with
      congestive heart failure.
AB  - BACKGROUND AND AIMS: Inflammation is part of the pathophysiology of congestive
      heart failure (CHF). However, little is known about the impact of the presence of
      systemic inflammatory disease (SID), defined as inflammatory syndrome with
      constitutional symptoms and involvement of at least two organs as co-morbidity on
      the clinical course and prognosis of patients with CHF. METHODS AND RESULTS: This
      is an analysis of all 622 patients included in TIME-CHF. After an 18 months
      follow-up, outcomes of patients with and without SID were compared. Primary
      endpoint was all-cause hospitalization free survival. Secondary endpoints were
      overall survival and CHF hospitalization free survival. At baseline, 38 patients
      had history of SID (6.1%). These patients had higher N-terminal pro brain
      natriuretic peptide and worse renal function than patients without SID. SID was a
      risk factor for adverse outcome [primary endpoint: hazard ratio (HR) = 1.73 (95%
      confidence interval: 1.18-2.55, P = 0.005); survival: HR = 2.60 (1.49-4.55, P =
      0.001); CHF hospitalization free survival: HR = 2.3 (1.45-3.65, P < 0.001)]. In
      multivariate models, SID remained the strongest independent risk factor for
      survival and CHF hospitalization free survival. CONCLUSION: In elderly patients
      with CHF, SID is independently accompanied with adverse outcome. Given the
      increasing prevalence of SID in the elderly population, these findings are
      clinically important for both risk stratification and patient management.

PMID- 24131550
TI  - Vaginal microbiome in women from Greenland assessed by microscopy and
      quantitative PCR.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a common condition, although its
      aetiology remains unexplained. The aim of this study was to analyse the
      composition of vaginal microbiota in women from Greenland to provide a
      quantitative description and improve the understanding of BV. METHODS: Self
      collected vaginal smears and swabs were obtained from 177 women. The vaginal
      smears were graded for BV according to Nugent's criteria. The vaginal swab
      samples were analysed by 19 quantitative PCRs (qPCRs) for selected vaginal
      bacteria and by PCR for four sexually transmitted infections (STIs). RESULTS:
      STIs were common: Mycoplasma genitalium 12%, Chlamydia trachomatis 7%, Neisseria
      gonorrhoeae 1%, and Trichomonas vaginalis 0.5%. BV was found in 45% of women, but
      was not associated with individual STIs. Seven of the 19 vaginal bacteria
      (Atopobium vaginae, Prevotella spp., Gardnerella vaginalis, BVAB2, Eggerthella
      like bacterium, Leptotrichia amnionii, and Megasphaera type 1) had areas under
      the receiver operating characteristic (ROC) curve > 85%, suggesting they are good
      predictors of BV according to Nugent. Prevotella spp. had the highest odds ratio
      for BV (OR 437; 95% CI 82-2779) in univariate analysis considering only specimens
      with a bacterial load above the threshold determined by ROC curve analysis as
      positive, as well as the highest adjusted odds ratio in multivariate logistic
      regression analysis (OR 4.4; 95% CI 1.4-13.5). BV could be subdivided into
      clusters dominated by a single or a few species together. CONCLUSIONS: BV by
      Nugent score was highly prevalent. Two of seven key species (Prevotella spp. and
      A. vaginae) remained significantly associated with BV in a multivariate model
      after adjusting for other bacterial species. G. vaginalis and Prevotella spp.
      defined the majority of BV clusters.

PMID- 24131551
TI  - Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an
      open-labeled clinical trial.
AB  - BACKGROUND: Currently, there are no effective medical treatment options to
      prevent the formation of heterotopic bones in fibrodysplasia ossificans
      progressiva (FOP). By the drug repositioning strategy, we confirmed that
      perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in
      model cells and mice. Here, we conducted a prospective study to assess the
      efficacy and safety of Pex in the treatment of FOP patients. METHODS: FOP
      patients in this open-label single-center study were treated with Pex for a total
      of 12 months, and followed up for 12 consecutive months after medication
      discontinuation. The safety of the treatment was assessed regularly by physical
      and blood examinations. The efficacy of Pex for preventing heterotopic
      ossifications was evaluated by the presence of flare-ups, measurements of serum
      bone markers, and changes in the total bone volume calculated by the three
      dimensional computed tomography (3D-CT) images. RESULTS: Five patients with an
      average age of 23.4 years were enrolled. Within safe doses of Pex administration
      in each individual, there were no drug-induced adverse effects during the
      medication phase. Three patients showed no intense inflammatory reactions during
      the study period, while two patients had acute flare-ups around the hip joint
      without evidence of trauma during the medication phase. In addition, one of them
      became progressively incapable of opening her mouth over the discontinuation
      phase. Serum levels of alkaline phosphatase (ALP) and bone specific ALP (BAP)
      were significantly and synchronously increased with the occurrence of flare-ups.
      Volumetric 3D-CT analysis demonstrated a significant increase in the total bone
      volume of Case 2 (378 cm(3)) and Case 3 (833 cm(3)) during the two-year study
      period. CONCLUSIONS: We could not prove the efficacy of oral Pex administration
      in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and
      BAP appear to be promising biomarkers for monitoring the development of ectopic
      ossifications and efficacy of the therapy. Quantification of change in the total
      bone volume by whole body CT scanning could be a reliable evaluation tool for
      disease progression in forthcoming clinical trials of FOP.

PMID- 24131552
TI  - Perturbed threat monitoring following a traumatic event predicts risk for post
      traumatic stress disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a chronic and difficult to
      treat psychiatric disorder. Objective, performance-based diagnostic markers that
      uniquely index risk for PTSD above and beyond subjective self-report markers
      could inform attempts to improve prevention and early intervention. We evaluated
      the predictive value of threat-related attention bias measured immediately after
      a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up.
      We measured the predictive contribution of attentional threat bias above and
      beyond that of the more established marker of risk for PTSD, self-reported
      psychological dissociation. METHOD: Dissociation symptoms and threat-related
      attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean
      age = 35.02 years, 356 males) within 24 h of admission to an emergency department
      (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow
      up using the Clinician-Administered PTSD Scale (CAPS). RESULTS: Self-reported
      dissociation symptoms significantly accounted for 16% of the variance in PTSD at
      follow-up, and attention bias toward threat significantly accounted for an
      additional 4% of the variance in PTSD. CONCLUSIONS: Threat-related attention bias
      can be reliably measured in the context of a hospital ED and significantly
      predicts risk for later PTSD. Possible mechanisms underlying the association
      between threat bias following a potentially traumatic event and risk for PTSD are
      discussed. The potential application of an attention bias modification treatment
      (ABMT) tailored to reduce risk for PTSD is suggested.

PMID- 24131553
TI  - Influence of mHealth interventions on gender relations in developing countries: a
      systematic literature review.
AB  - INTRODUCTION: Research has shown that mHealth initiatives, or health programs
      enhanced by mobile phone technologies, can foster women's empowerment. Yet, there
      is growing concern that mobile-based programs geared towards women may exacerbate
      gender inequalities. METHODS: A systematic literature review was conducted to
      examine the empirical evidence of changes in men and women's interactions as a
      result of mHealth interventions. To be eligible, studies had to have been
      published in English from 2002 to 2012, conducted in a developing country,
      included an evaluation of a mobile health intervention, and presented findings on
      resultant dynamics between women and men. The search strategy comprised four
      electronic bibliographic databases in addition to a manual review of the
      reference lists of relevant articles and a review of organizational websites and
      journals with recent mHealth publications. The methodological rigor of selected
      studies was appraised by two independent reviewers who also abstracted data on
      the study's characteristics. Iterative thematic analyses were used to synthesize
      findings relating to gender-transformative and non-transformative experiences.
      RESULTS: Out of the 173 articles retrieved for review, seven articles met the
      inclusion criteria and were retained in the final analysis. Most mHealth
      interventions were SMS-based and conducted in sub-Saharan Africa on topics
      relating to HIV/AIDS, sexual and reproductive health, health-based
      microenterprise, and non-communicable diseases. Several methodological
      limitations were identified among eligible quantitative and qualitative studies.
      The current literature suggests that mobile phone programs can influence gender
      relations in meaningfully positive ways by providing new modes for couple's
      health communication and cooperation and by enabling greater male participation
      in health areas typically targeted towards women. MHealth initiatives also
      increased women's decision-making, social status, and access to health resources.
      However, programmatic experiences by design may inadvertently reinforce the
      digital divide, and perpetuate existing gender-based power imbalances. Domestic
      disputes and lack of spousal approval additionally hampered women's
      participation. CONCLUSION: Efforts to scale-up health interventions enhanced by
      mobile technologies should consider the implementation and evaluation imperative
      of ensuring that mHealth programs transform rather than reinforce gender
      inequalities. The evidence base on the effect of mHealth interventions on gender
      relations is weak, and rigorous research is urgently needed.

PMID- 24131554
TI  - An audit of eye dryness and corneal abrasion in ICU patients in Iran.
AB  - BACKGROUND: The use of sedation and muscle relaxants can predispose intensive
      care unit (ICU) patients to poor eyelid closure and eye disorders. These
      complications may not get the nursing care and attention that they require; this
      and the predisposing factors need to be further investigated. AIMS AND
      OBJECTIVES: The aim of this audit was to use the standard eye-care technique and
      determine the incidence of eye dryness and corneal abrasion, on day 5 after
      admission, in comatose patients in the ICU. DESIGN AND METHODS: This was an
      audit, in the four ICUs in two teaching hospitals in the cities of Kashan and
      Tehran. An ophthalmologist examined the corneal abrasion and eye dryness on the
      day of admission and then day 5. The eye-care method and other variables such as
      sex and age were also recorded. Statistical tests of chi(2) , spearman and
      multiple linear regressions were used to determine the relationships between
      variables. RESULTS: Eighty-seven patients participated in the audit. On day 5, 28
      patients (32.2%) had dry eyes and 12 patients had developed corneal abrasion
      (13.8%). The mean of Schirmer tear value on admission was 21 +/- 4.5 mm. This
      value decreased to 16.1 +/- 5.6 mm on day 5. About 10.3% of patients who received
      eye lubricant products, and 20.7% of those receiving adhesive tape as eye-care
      method developed corneal abrasion. CONCLUSIONS: Corneal abrasion and eye dryness
      were common problems in ICU patients. Eye dryness was the main risk factor for
      the development of corneal abrasion. Patients receiving adhesive tape as an eye
      care method were twice more likely to develop corneal abrasion. RELEVANCE TO
      CLINICAL PRACTICE: Eye care and eye assessment should be essential parts of
      nursing care for patients in ICU. To prevent corneal abrasion, using eye
      lubricants is more effective than closing eyes by adhesive tape.

PMID- 24131556
TI  - Multiple sclerosis severity score in a cohort of Moroccan patients.

PMID- 24131555
TI  - Reaching hard-to-reach individuals: Nonselective versus targeted outbreak
      response vaccination for measles.
AB  - Current mass vaccination campaigns in measles outbreak response are nonselective
      with respect to the immune status of individuals. However, the heterogeneity in
      immunity, due to previous vaccination coverage or infection, may lead to
      potential bias of such campaigns toward those with previous high access to
      vaccination and may result in a lower-than-expected effective impact. During the
      2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination
      occurred achieved a measureable effective campaign impact (i.e., a reduction in
      measles cases in the targeted age groups greater than that observed in
      nonvaccinated districts). Simulation models suggest that selective campaigns
      targeting hard-to-reach individuals are of greater benefit, particularly in
      highly vaccinated populations, even for low target coverage and with late
      implementation. However, the choice between targeted and nonselective campaigns
      should be context specific, achieving a reasonable balance of feasibility, cost,
      and expected impact. In addition, it is critical to develop operational
      strategies to identify and target hard-to-reach individuals.

PMID- 24131557
TI  - Software-supported evaluation of gastric motility in MRI: a feasibility study.
AB  - INTRODUCTION: The aim of this study was to evaluate the feasibility of dedicated
      motility assessment software for quantitative evaluation of basic gastric
      motility and to validate it using manual measurements. METHODS: Ten patients (5
      males/5 females, mean 41 years) out of a previous series of small bowel MR
      enterography examinations with well visible stomachs were included in this
      Institutional Reviews Board approved, retrospective study. MRI (1.5-T, Siemens
      Sonata) was performed after standardised oral preparation (3% aqueous mannitol
      over 1 h). Coronal 2DtrueFISP (TR 283.8/TE 1.89/FOV400/10 mm slice) motility
      acquisitions covering the entire abdomen were performed in apnoea. For each
      patient, image analysis for assessment of gastric motility was performed both
      manually and using the dedicated software either the proximal (n = 5) or in the
      distal (n = 5) gastric corpus. The main quantitative endpoints (amplitude,
      frequency) describing gastric motility were compared using (paired) Student's t
      Test. RESULTS: All motility curves qualitatively matched each other (10/10). No
      significant differences (P > 0.05) were found for amplitudes (mean: 18.17 mm
      manual; 17.78 mm software), contraction frequencies (5.1/min; 4.7/min) and mean
      lumen diameters (34.12 mm; 33.13 mm), respectively. Mean duration for a single
      measurement was significantly (P < 0.001) lower with the software (6.40 min
      manual technique; 1.40 min software assisted). CONCLUSIONS: The software proves
      to be feasible for fast and accurate measurement of basic gastric motility
      parameters providing comparable data in comparison to manual assessment methods.
      It might help to reduce the time needed for assessment of relevant
      characteristics of gastric motility.

PMID- 24131558
TI  - An analysis of socio-demographic patterns in child malnutrition trends using
      Ghana demographic and health survey data in the period 1993-2008.
AB  - BACKGROUND: A small but growing body of research indicates that progress in
      reducing child malnutrition is substantially uneven from place to place, even
      down to the district level within countries. Yet child malnutrition prevalence
      and trend estimates available for public health planning are mostly available
      only at the level of global regions and/or at country level. To support carefully
      targeted intervention to reduce child malnutrition, public health planners and
      policy-makers require access to more refined prevalence data and trend analyses
      than are presently available. Responding to this need in Ghana, this report
      presents trends in child malnutrition prevalence in socio-demographic groups
      within the country's geographic regions. METHODS: The study uses the Ghana
      Demographic and Health Surveys (GDHS) data. The GDHS are nationally
      representative cross-sectional surveys that have been carried out in many
      developing countries. These surveys constitute one of the richest sources of
      information currently available to examine time trends in child malnutrition.
      Data from four surveys were used for the analysis: 1993, 1998, 2003 and 2008.
      RESULTS: The results show statistically significant declining trends at the
      national level for stunting (F (1, 7204) = 7.89, p <= .005), underweight (F (1,
      7441) = 44.87, p <= .001) and wasting (F (1, 7130) = 6.19, p <= .013). However,
      analyses of the sex-specific trends revealed that the declining trends in
      stunting and wasting were significant among males but not among females. In
      contrast to the national trend, there were significantly increasing trends in
      stunting for males (F (1, 2004) = 3.92, p <= .048) and females (F (1, 2004) =
      4.34, p <= .037) whose mothers had higher than primary education, while the
      trends decreased significantly for males and females whose mothers had no
      education. CONCLUSIONS: At the national level in Ghana, child malnutrition is
      significantly declining. However, the aggregate national trend masks important
      deviations in certain socio-demographic segments, including worsening levels of
      malnutrition. This paper shows the importance of disaggregated analyses of
      national child malnutrition data, to unmask underlying geographic and socio
      demographic differences.

PMID- 24131562
TI  - From sub cellular to community level: toxicity of glutaraldehyde to several
      aquatic organisms.
AB  - The biocide glutaraldehyde (GA) is widely used as a disinfectant and sterilizing
      agent against bacteria and virus in hospital and veterinary facilities. GA or its
      metabolites may reach aquatic ecosystems due to incomplete or inadequate
      treatment of wastewaters. Data about GA effects at lethal and a sub lethal level
      to non-target organisms is needed so that a risk assessment to aquatic ecosystems
      can be done. Thus, in this work a battery of toxicity tests with primary
      producers, primary consumers and secondary consumers were performed and a species
      sensitive distribution (SSD) for GA was built. Moreover, effects on biomarkers
      (catalase, lactate dehydrogenase, glutathione-S-transferase, and cholinesterase)
      were measured in Danio rerio embryos and adults. Primary consumers
      (Thamnocephalus platyurus 24h - EC50=3.6 mg/l; Daphnia magna 48 h - EC50=6.6
      mg/l) and D. rerio adults (96 h - LC50=5.5mg/l) were slightly more sensitive to
      GA than D. rerio embryos (96 h - LC50=22.2mg/l) and primary producers (Lemna
      minor 168 h - EC50=73.8 mg/l; Pseudokirchneriella subcapitata 72h -
      EC50=12.3mg/l; Chlamydomonas reinhardtii 72 h - EC50=14.6 mg/l; Chlorella
      vulgaris 72 h - EC50=31.3mg/l). However, no significant differences between the
      trophic levels were found and general HC5 and HC50 values of 0.6 and 11.4 mg/l
      were respectively estimated. Despite the low GA toxicity to D. rerio embryos,
      hatching delay and malformations were found (96 h - EC50=11.9 mg/l). For
      biomarkers, an inhibition of lactate dehydrogenase activity was observed in
      embryos whereas an inhibition in catalase, lactate dehydrogenase and glutathione
      S-transferase activities was observed in adults. Thus, GA is moderately toxic
      (doses>1mg/l) to aquatic organisms, independently of the trophic level. However,
      considering the varied range of effects depending on the life stage and organism
      tested and relatively low HC5 value of 0.6 mg/l, mesocosm and chronic toxicity
      tests seem to be the next step in direction of more realistic scenarios of GA
      risk assessment in aquatic ecosystems.

PMID- 24131563
TI  - Genome-wide high resolution parental-specific DNA and histone methylation maps
      uncover patterns of imprinting regulation in maize.
AB  - Genetic imprinting is a specific epigenetic phenomenon in which a subset of genes
      is expressed depending on their parent-of-origin. Two types of chromatin
      modifications, DNA methylation and histone modification, are generally believed
      to be involved in the regulation of imprinting. However, the genome-wide
      correlation between allele-specific chromatin modifications and imprinted gene
      expression in maize remains elusive. Here we report genome-wide high resolution
      allele-specific maps of DNA methylation and histone H3 lysine 27 trimethylation
      (H3K27me3) in maize endosperm. For DNA methylation, thousands of parent-of-origin
      dependent differentially methylated regions (pDMRs) were identified. All pDMRs
      were uniformly paternally hypermethylated and maternally hypomethylated. We also
      identified 1131 allele-specific H3K27me3 peaks that are preferentially present in
      the maternal alleles. Maternally expressed imprinted genes (MEGs) and paternally
      expressed imprinted genes (PEGs) had different patterns of allele-specific DNA
      methylation and H3K27me3. Allele-specific expression of MEGs was not directly
      related to allele-specific H3K27me3, and only a subset of MEGs was associated
      with maternal-specific DNA demethylation, which was primarily located in the
      upstream and 5' portion of gene body regions. In contrast, allele-specific
      expression of a majority of PEGs was related to maternal-specific H3K27me3, with
      a subgroup of PEGs also associated with maternal-specific DNA demethylation. Both
      pDMRs and maternal H3K27me3 peaks associated with PEGs are enriched in gene body
      regions. Our results indicate highly complex patterns of regulation on genetic
      imprinting in maize endosperm. 

PMID- 24131565
TI  - Relationship between financial speculation and food prices or price volatility:
      applying the principles of evidence-based medicine to current debates in Germany.
AB  - There is an unresolved debate about the potential effects of financial
      speculation on food prices and price volatility. Germany's largest financial
      institution and leading global investment bank recently decided to continue
      investing in agricultural commodities, stating that there is little empirical
      evidence to support the notion that the growth of agricultural-based financial
      products has caused price increases or volatility. The statement is supported by
      a recently published literature review, which concludes that financial
      speculation does not have an adverse effect on the functioning of the
      agricultural commodities market. As public health professionals concerned with
      global food insecurity, we have appraised the methodological quality of the
      review using a validated and reliable appraisal tool. The appraisal revealed
      major shortcomings in the methodological quality of the review. These were
      particularly related to intransparencies in the search strategy and in the
      selection/presentation of studies and findings; the neglect of the possibility of
      publication bias; a lack of objective or rigorous criteria for assessing the
      scientific quality of included studies and for the formulation of conclusions.
      Based on the results of our appraisal, we conclude that it is not justified to
      reject the hypothesis that financial speculation might have adverse effects on
      food prices/price volatility. We hope to initiate reflections about scientific
      standards beyond the boundaries of disciplines and call for high quality,
      rigorous systematic reviews on the effects of financial speculation on food
      prices or price volatility. 

PMID- 24131564
TI  - Integrative transcriptome sequencing identifies trans-splicing events with
      important roles in human embryonic stem cell pluripotency.
AB  - Trans-splicing is a post-transcriptional event that joins exons from separate pre
      mRNAs. Detection of trans-splicing is usually severely hampered by experimental
      artifacts and genetic rearrangements. Here, we develop a new computational
      pipeline, TSscan, which integrates different types of high-throughput long-/short
      read transcriptome sequencing of different human embryonic stem cell (hESC) lines
      to effectively minimize false positives while detecting trans-splicing. Combining
      TSscan screening with multiple experimental validation steps revealed that most
      chimeric RNA products were platform-dependent experimental artifacts of RNA
      sequencing. We successfully identified and confirmed four trans-spliced RNAs,
      including the first reported trans-spliced large intergenic noncoding RNA
      ("tsRMST"). We showed that these trans-spliced RNAs were all highly expressed in
      human pluripotent stem cells and differentially expressed during hESC
      differentiation. Our results further indicated that tsRMST can contribute to
      pluripotency maintenance of hESCs by suppressing lineage-specific gene expression
      through the recruitment of NANOG and the PRC2 complex factor, SUZ12. Taken
      together, our findings provide important insights into the role of trans-splicing
      in pluripotency maintenance of hESCs and help to facilitate future studies into
      trans-splicing, opening up this important but understudied class of post
      transcriptional events for comprehensive characterization. 

PMID- 24131566
TI  - Dominantly Inherited Alzheimer Network: facilitating research and clinical
      trials.
AB  - The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of
      individuals at risk for developing autosomal dominant Alzheimer's disease (AD).
      Its primary aims are to investigate the temporal ordering of AD
      pathophysiological changes that occur in asymptomatic mutation carriers and to
      identify those markers that herald the transition from cognitive normality to
      symptomatic AD. DIAN participants undergo longitudinal evaluations, including
      clinical and cognitive assessments and measurements of molecular and imaging AD
      biomarkers. This review details the unique attributes of DIAN as a model AD
      biomarker study and how it provides the infrastructure for innovative research
      projects, including clinical trials. The recent design and launch of the first
      anti-amyloid-beta secondary prevention trial in AD, led by the related DIAN
      Trials Unit, also are discussed. 

PMID- 24131567
TI  - The course of the working alliance during virtual reality and exposure group
      therapy for social anxiety disorder.
AB  - BACKGROUND: Psychoanalytic theory and some empirical research suggest the working
      alliance follows a "rupture and repair" pattern over the course of therapy, but
      given its emphasis on collaboration, cognitive behavioral therapy may yield a
      different trajectory. AIMS: The current study compares the trajectory of the
      working alliance during two types of cognitive behavioral therapy for social
      anxiety disorder - virtual reality exposure therapy (VRE) and exposure group
      therapy (EGT), one of which (VRE) has been proposed to show lower levels of
      working alliance due to the physical barriers posed by the technology (e.g. no
      eye contact with therapist during exposure). METHOD: Following randomization,
      participants (N = 63) diagnosed with social anxiety disorder received eight
      sessions of manualized EGT or individual VRE and completed a standardized self
      report measure of working alliance after each session. RESULTS: Hierarchical
      linear modeling showed overall high levels of working alliance that changed in
      rates of growth over time; that is, increases in working alliance scores were
      steeper at the beginning of therapy and slowed towards the end of therapy. There
      were no differences in working alliance between the two treatment groups.
      CONCLUSION: Results neither support a rupture/repair pattern nor the idea that
      the working alliance is lower for VRE participants. Findings are consistent with
      the idea that different therapeutic approaches may yield different working
      alliance trajectories.

PMID- 24131568
TI  - Cutaneous polyarteritis nodosa presenting with digital gangrene and breast ulcer.

PMID- 24131569
TI  - Frailty and falls among adult patients undergoing chronic hemodialysis: a
      prospective cohort study.
AB  - BACKGROUND: Patients undergoing hemodialysis are at high risk of falls, with
      subsequent complications including fractures, loss of independence,
      hospitalization, and institutionalization. Factors associated with falls are
      poorly understood in this population. We hypothesized that insights derived from
      studies of the elderly might apply to adults of all ages undergoing hemodialysis;
      we focused on frailty, a phenotype of physiological decline strongly associated
      with falls in the elderly. METHODS: In this prospective, longitudinal study of 95
      patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with
      future falls was explored using adjusted Poisson regression. Frailty was
      classified using the criteria established by Fried et al., as a combination of
      five components: shrinking, weakness, exhaustion, low activity, and slowed
      walking speed. RESULTS: Over a median 6.7-month period of longitudinal follow-up,
      28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and
      older) experienced a fall. After adjusting for age, sex, race, comorbidity,
      disability, number of medications, marital status, and education, frailty
      independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of
      falls. This relationship between frailty and falls did not differ for younger and
      older adults (P=0.57). CONCLUSIONS: Frailty, a validated construct in the
      elderly, was a strong and independent predictor of falls in adults undergoing
      hemodialysis, regardless of age. Our results may aid in identifying frail
      hemodialysis patients who could be targeted for multidimensional fall prevention
      strategies.

PMID- 24131570
TI  - Student nurses in critical care: benefits and challenges of critical care as a
      learning environment for student nurses.
AB  - AIM: This article is a literature view of student nurses' experiences of critical
      care and the value of their experience to the nursing community. To explore the
      literature in relation to the value of critical care as a learning environment,
      the experiences and perceptions of student nurses in critical care and the impact
      of mentors on the experience. BACKGROUND: The shortage of critical care nurses
      and increasing numbers of acutely ill patients being cared for outside critical
      care areas has highlighted the importance of nurses being equipped with
      appropriate knowledge and skills to care for such patients. Student nurses have
      been experiencing critical care for many years and though it is accepted that it
      can be a stressful environment, there has been little empirical evidence of this.
      As anxiety has been said to interfere with learning, how much of an impact can
      this have and can anything be done about it? SEARCH STRATEGY: Using Medline,
      CINAHL and British Nursing Index (BNI) and search terms including nursing
      students or student nurses, critical or intensive care and perceptions,
      expectations or pre-conceptions, a literature search was carried out. Some
      articles explored registered nurses experiences, despite the titles, so this was
      set as an exclusion criteria. CONCLUSIONS: Critical care offers a wealth of
      learning opportunities which are only available in high acuity areas. Though
      students can be very anxious before commencing their placements, mentors and
      higher education play an important part in helping them overcome this. The
      challenge is how to work together to provide effective support systems for the
      benefit of the students.

PMID- 24131571
TI  - A case-control study of maternal bathing habits and risk for birth defects in
      offspring.
AB  - BACKGROUND: Nearly all women shower or take baths during early pregnancy;
      however, bathing habits (i.e., shower and bath length and frequency) may be
      related to the risk of maternal hyperthermia and exposure to water disinfection
      byproducts, both of which are suspected to increase risk for multiple types of
      birth defects. Thus, we assessed the relationships between bathing habits during
      pregnancy and the risk for several nonsyndromic birth defects in offspring.
      METHODS: Data for cases with one of 13 types of birth defects and controls from
      the National Birth Defects Prevention Study delivered during 2000-2007 were
      evaluated. Logistic regression analyses were conducted separately for each type
      of birth defect. RESULTS: There were few associations between shower frequency or
      bath frequency or length and risk for birth defects in offspring. The risk for
      gastroschisis in offspring was increased among women who reported showers lasting
      >=15 compared to <15 minutes (adjusted odds ratio: 1.43, 95% confidence interval:
      1.18-1.72). In addition, we observed modest increases in the risk for spina
      bifida, cleft lip with or without cleft palate, and limb reduction defects in
      offspring of women who showered >=15 compared to <15 minutes. The results of
      comparisons among more specific categories of shower length (i.e., <15 minutes
      versus 15-19, 20-29, and >= 30 minutes) were similar. CONCLUSIONS: Our findings
      suggest that shower length may be associated with gastroschisis, but the modest
      associations with other birth defects were not supported by analyses of bath
      length or bath or shower frequency. Given that showering for >=15 minutes during
      pregnancy is very common, further evaluation of the relationship between maternal
      showering habits and birth defects in offspring is worthwhile.

PMID- 24131572
TI  - Clinical evidence for orphan medicinal products-a cause for concern?
AB  - BACKGROUND: The difficulties associated with organising clinical studies for
      orphan medicinal products (OMPs) are plentiful. Recent debate on the long-term
      effectiveness of some OMPs, led us to question whether the initial standards for
      clinical evidence for OMPs, set by the European Medicines Agency (EMA) at the
      time of marketing authorization, are too low. Therefore, the aim of this study
      was to quantitatively evaluate the characteristics and quality of clinical
      evidence that is presented for OMPs to obtain marketing authorization in Europe,
      using the new and validated COMPASS tool. METHODS: We quantitatively assessed the
      characteristics and quality of clinical evidence of the pivotal studies of 64
      OMPs as described in the European Public Assessment Report and/or the Scientific
      Discussion document prepared by the Committee for Human Medicinal Products of the
      EMA. RESULTS: The 64 OMPs were altogether authorized for 78 orphan indications,
      for which 117 studies were identified as 'pivotal' or 'main' studies. In
      approximately two thirds of the studies, the allocation was randomized (64.8%)
      and a control arm was used (68.5%). Half of the studies applied some type of
      blinding. Only a minority (26.9%) of the studies included a Quality-of-Life (QoL)
      related endpoint, of which a third claim an improvement in QoL. Upon analyzing
      the quality of reporting, we found that some aspects (i.e. the endpoints, the
      sampling criteria, and the interventions) are well described, whereas other items
      (i.e. a description of the patients and of potential biases) are not reported for
      all studies. CONCLUSIONS: In conclusion, the pivotal studies that are the basis
      for marketing authorization of OMPs are a cause for concern, as they exhibit
      methodological flaws i.e. the lack of QoL-related endpoints as outcome, lack of
      blinding in the study design and the use of surrogate endpoints. Additionally,
      there are shortcomings in the reporting of those studies that complicate the
      interpretation. A more demanding regulatory process for OMPs is needed to guide
      evidence-based clinical decision-making.

PMID- 24131573
TI  - AKT is involved in granulosa cell autophagy regulation via mTOR signaling during
      rat follicular development and atresia.
AB  - In this study, we examined whether granulosa cell autophagy during follicular
      development and atresia was regulated by the class I phosphoinositide-3
      kinase/protein kinase B (AKT) pathway, which is known to control the activity of
      mammalian target of rapamycin (mTOR), a major negative regulator of autophagy.
      Ovaries and granulosa cells were obtained using an established gonadotropin
      primed immature rat model that induces follicular development and atresia.
      Autophagy was evaluated by measuring the expression level of microtubule
      associated protein light chain 3-II (LC3-II) using western blots and
      immunohistochemistry. The activity of AKT and mTOR was also examined by observing
      the phosphorylation of AKT and ribosomal protein S6 kinase (S6K) respectively.
      After gonadotropin injection, LC3-II expression was suppressed and
      phosphorylation of AKT and S6K increased in rat granulosa cells. By contrast,
      gonadotropin withdrawal by metabolic clearance promoted LC3-II expression and
      decreased phosphorylation of AKT and S6K. In addition, in-vitro FSH treatment of
      rat granulosa cells also indicated inhibition of LC3-II expression accompanied by
      a marked increase in phosphorylation of AKT and S6K. Inhibition of AKT
      phosphorylation using AKT inhibitor VIII suppressed FSH-mediated phosphorylation
      of S6K, followed by an increase in LC3-II expression. Furthermore, co-treatment
      with FSH and AKT inhibitor increased the levels of apoptosis and cell death of
      granulosa cells compared with the single treatment with FSH. Taken together, our
      findings indicated that AKT-mediated activation of mTOR suppresses granulosa cell
      autophagy during follicular development and is involved in the regulation of
      apoptotic cell death. 

PMID- 24131574
TI  - Dispelling myths about rare disease registry system development.
AB  - Rare disease registries (RDRs) are an essential tool to improve knowledge and
      monitor interventions for rare diseases. If designed appropriately, patient and
      disease related information captured within them can become the cornerstone for
      effective diagnosis and new therapies. Surprisingly however, registries possess a
      diverse range of functionality, operate in different, often-times incompatible,
      software environments and serve various, and sometimes incongruous, purposes.
      Given the ambitious goals of the International Rare Diseases Research Consortium
      (IRDiRC) by 2020 and beyond, RDRs must be designed with the agility to evolve and
      efficiently interoperate in an ever changing rare disease landscape, as well as
      to cater for rapid changes in Information Communication Technologies. In this
      paper, we contend that RDR requirements will also evolve in response to a number
      of factors such as changing disease definitions and diagnostic criteria, the
      requirement to integrate patient/disease information from advances in either
      biotechnology and/or phenotypying approaches, as well as the need to adapt
      dynamically to security and privacy concerns. We dispel a number of myths in RDR
      development, outline key criteria for robust and sustainable RDR implementation
      and introduce the concept of a RDR Checklist to guide future RDR development. 

PMID- 24131575
TI  - Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal
      dopaminergic neurons.
AB  - High-frequency stimulation of the nucleus accumbens, also known as deep brain
      stimulation (DBS), is currently used to alleviate obsessive compulsive symptoms
      when pharmacotherapy is ineffective. However, the mechanism by which DBS achieves
      its therapeutic actions is not understood. Imaging studies and the actions of
      dopaminergic drugs in untreated patients suggest that the dopamine (DA) system
      likely plays a role in the pathophysiology of obsessive compulsive disorder.
      Therefore, we examined whether DBS would impact the DA system as a potential
      component of its therapeutic actions. The activity of DA neurons in the
      substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were
      recorded in anesthetized rats under high-frequency stimulation. DA neuron
      activity was measured in terms of number of neurons firing, average firing rate
      and firing pattern. DBS of the nucleus accumbens core did not significantly
      affect VTA activity or discharge pattern. On the other hand, DBS caused a potent
      decrease in the number of SNc DA neurons firing spontaneously. Such an effect
      could contribute to the disruption of pathological habit formation in the SNc
      dorsal striatal projection system that may have therapeutic implications for the
      treatment of obsessive compulsive disorder. 

PMID- 24131576
TI  - Pharmaceutical digital marketing and governance: illicit actors and challenges to
      global patient safety and public health.
AB  - BACKGROUND: Digital forms of direct-to-consumer pharmaceutical marketing (eDTCA)
      have globalized in an era of free and open information exchange. Yet, the
      unregulated expansion of eDTCA has resulted in unaddressed global public health
      threats. Specifically, illicit online pharmacies are engaged in the sale of
      purportedly safe, legitimate product that may in fact be counterfeit or
      substandard. These cybercriminal actors exploit available eDTCA mediums over the
      Internet to market their suspect products globally. Despite these risks, a
      detailed assessment of the public health, patient safety, and cybersecurity
      threats and governance mechanisms to address them has not been conducted.
      DISCUSSION: Illicit online pharmacies represent a significant global public
      health and patient safety risk. Existing governance mechanisms are insufficient
      and include lack of adequate adoption in national regulation, ineffective
      voluntary governance mechanisms, and uneven global law enforcement efforts that
      have allowed proliferation of these cybercriminals on the web. In order to
      effectively address this multistakeholder threat, inclusive global governance
      strategies that engage the information technology, law enforcement and public
      health sectors should be established. SUMMARY: Effective global "eHealth
      Governance" focused on cybercrime is needed in order to effectively combat
      illicit online pharmacies. This includes building upon existing Internet
      governance structures and coordinating partnership between the UN Office of Drugs
      and Crime that leads the global fight against transnational organized crime and
      the Internet Governance Forum that is shaping the future of Internet governance.
      Through a UNODC-IGF governance mechanism, investigation, detection and
      coordination of activities against illicit online pharmacies and their misuse of
      eDTCA can commence.

PMID- 24131577
TI  - Exposure to aircraft and road traffic noise and associations with heart disease
      and stroke in six European countries: a cross-sectional study.
AB  - BACKGROUND: Although a number of studies have found an association between
      aircraft noise and hypertension, there is a lack of evidence on associations with
      other cardiovascular disease. For road traffic noise, more studies are available
      but the extent of possible confounding by air pollution has not been established.
      METHODS: This study used data from the Hypertension and Environmental Noise near
      Airports (HYENA) study. Cross-sectional associations between self-reported 'heart
      disease and stroke' and aircraft noise and road traffic noise were examined using
      data collected between 2004 and 2006 on 4712 participants (276 cases), who lived
      near airports in six European countries (UK, Germany, Netherlands, Sweden,
      Greece, Italy). Data were available to assess potential confounding by NO2 air
      pollution in a subsample of three countries (UK, Netherlands, Sweden). RESULTS:
      An association between night-time average aircraft noise and 'heart disease and
      stroke' was found after adjustment for socio-demographic confounders for
      participants who had lived in the same place for >= 20 years (odds ratio (OR):
      1.25 (95% confidence interval (CI) 1.03, 1.51) per 10 dB (A)); this association
      was robust to adjustment for exposure to air pollution in the subsample. 24 hour
      average road traffic noise exposure was associated with 'heart disease and
      stroke' (OR: 1.19 (95% CI 1.00, 1.41), but adjustment for air pollution in the
      subsample suggested this may have been due to confounding by air pollution.
      Statistical assessment (correlations and variance inflation factor) suggested
      only modest collinearity between noise and NO2 exposures. CONCLUSIONS: Exposure
      to aircraft noise over many years may increase risks of heart disease and stroke,
      although more studies are needed to establish how much the risks associated with
      road traffic noise may be explained by air pollution.

PMID- 24131578
TI  - Risk of tuberculosis with anti-tumor necrosis factor-alpha therapy: substantially
      higher number of patients at risk in Asia.
AB  - AIM: To assess the potential risk of tuberculosis (TB) in patients treated with
      anti-tumor necrosis factor-alpha (TNF-alpha) agents in Asia. METHODS: Absolute
      risk increase (ARI) of TB was estimated for three widely used anti-TNF-alpha
      therapies using published standardized incidence ratios (SIR) from the French
      Research Axed on Tolerance of bIOtherapies registry and incidence (absolute risk
      [AR]) of TB in Asia. Assuming an association of increased TB risk with anti-TNF
      alpha therapy and country TB AR (incidence), the ARI of TB by country was
      calculated by multiplying the SIR of the anti-TNF-alpha therapy by the country's
      TB AR. The numbers needed to harm (NNH) for each anti-TNF-alpha agent and numbers
      needed to treat (NNT) to reduce one TB event using etanercept therapy instead of
      adalimumab or infliximab were also calculated for each country. RESULTS: The ARI
      of TB with anti-TNF-alpha therapies in Asian countries is substantially higher
      than Western Europe and North America and the difference between etanercept
      versus the monoclonal antibodies becomes more evident. The NNH for Asian
      countries ranged from 8 to 163 for adalimumab, 126 to 2646 for etanercept and 12
      to 256 for infliximab. The NNT to reduce one TB event using etanercept instead of
      adalimumab therapy ranged from 8 to 173, and using etanercept instead of
      infliximab therapy the NNT ranged from 13 to 283. CONCLUSION: Higher numbers of
      patients are at risk of developing TB with anti-TNF-alpha therapy in Asia
      compared with Western Europe and North America. The relative lower risk of TB
      with etanercept may be particularly relevant for Asia, an endemic area for TB.

PMID- 24131579
TI  - Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat
      model.
AB  - BACKGROUND: Few studies have considered hormonal influences, particularly vitamin
      D, on healing. HYPOTHESIS: Vitamin D deficiency would have a negative effect on
      the structure of the healing tendon-bone interface in a rat model and would
      result in decreased tendon attachment strength. STUDY DESIGN: Controlled
      laboratory study. METHODS: Vitamin D deficiency was induced in 28 male Sprague
      Dawley rats using a specialized vitamin D-deficient diet and ultraviolet light
      restriction. Serum levels of vitamin D were measured after 6 weeks. These vitamin
      D-deficient animals (experimental group) plus 32 rats with normal vitamin D
      levels (controls) underwent unilateral detachment of the right supraspinatus
      tendon from the greater tuberosity of the humerus, followed by immediate repair
      using bone tunnel suture fixation. The animals were sacrificed at 2- and 4-week
      intervals after surgery for biomechanical analysis. A paired t test was used to
      compare serum vitamin D levels at day 0 and at 6 weeks. A nonparametric Mann
      Whitney U test was used to compare load-to-failure and stiffness values between
      the experimental group and controls. Bone density and new bone formation at the
      tendon insertion site on the greater tuberosity were assessed with micro-computed
      tomography (CT). The organization of collagen tissue, new bone formation,
      vascularity at the tendon-bone interface, fibrocartilage at the tendon-bone
      interface, and collagen fiber continuity between the tendon and bone tissue were
      evaluated with safranin O and picrosirius red staining. RESULTS: Blood draws
      confirmed vitamin D deficiency at 6 weeks compared with time zero/baseline for
      rats in the experimental group (10.9 ng/mL vs 6.5 ng/mL, respectively; P < .001).
      Biomechanical testing demonstrated a significant decrease in load to failure in
      the experimental group compared with controls at 2 weeks (5.8 +/- 2.0 N vs 10.5
      +/- 4.4 N, respectively; P < .006). There was no difference in stiffness at 2
      weeks between the control and experimental groups. At 4 weeks, there was no
      significant difference in load to failure or stiffness between the control and
      experimental groups. Histological analysis showed less bone formation and less
      collagen fiber organization in the vitamin D-deficient specimens at 4 weeks as
      compared with controls. Micro-CT analysis showed no significant difference
      between groups for total mineral density and bone volume fraction of cortical,
      whole, or trabecular bone at 4 weeks. CONCLUSION: The biomechanical and
      histological data from this study suggest that low vitamin D levels may
      negatively affect early healing at the rotator cuff repair site. CLINICAL
      RELEVANCE: It is estimated that 1 billion people worldwide are vitamin D
      deficient. In the deficient state, acutely injured rotator cuffs may have a
      reduced ability for tendon healing. Further studies are needed to determine the
      exact mechanism by which vitamin D affects tendon healing and whether vitamin D
      supplementation can improve rotator cuff tendon healing and reduce the incidence
      of retears.

PMID- 24131580
TI  - The meaning and importance of vigilant attendance for the relatives of intensive
      care unit patients.
AB  - AIM: To explore the meaning of vigilant attendance for relatives of critically
      ill patients in Greece. BACKGROUND: A plethora of international research has
      identified proximity to the patient to be a major concern for relatives of
      critically ill patients. Greece however follows a strict visiting policy in
      intensive care units (ICUs) so Greek relatives spend great amounts of time just
      outside the ICUs. DESIGN: This qualitative study adopted the social
      constructionist version of grounded theory. METHOD: Data were collected from
      three ICUs in Athens through in depth interviews with 25 informants and
      approximately 10 h of observations outside the ICUs on 159 relatives. FINDINGS:
      Vigilant attendance was one of the main coping mechanisms identified for
      relatives. Four subcategories were found to comprise vigilant attendance: (1)
      being as close as possible to feel relief, (2) being there to find out what is
      going on, (3) monitoring changes in the loved one and making own diagnosis and
      (4) interacting with the ICU professionals. CONCLUSION: Vigilant attendance
      describes the way in which relatives in Greece stayed outside the ICUs. Relatives
      felt satisfaction from being close as the best alternative for not actually being
      inside the ICU and they tried to learn what was going on by alternative methods.
      By seeing the patients, relatives were also able to make their own diagnoses and
      could therefore avoid relying solely on information given to them. However, a
      prerequisite for successful vigilant attendance was to get on well with doctors
      and nurses. RECOMMENDATIONS FOR CLINICAL PRACTICE: Changes in visiting policies
      in Greece are needed to meet the needs of relatives adequately. Recommendations
      for changes with minimal investment of time and funding are made.

PMID- 24131581
TI  - Whole genome methylation array analysis reveals new aspects in Balkan endemic
      nephropathy etiology.
AB  - BACKGROUND: Balkan endemic nephropathy (BEN) represents a chronic progressive
      interstitial nephritis in striking correlation with uroepithelial tumours of the
      upper urinary tract. The disease has endemic distribution in the Danube river
      regions in several Balkan countries.DNA methylation is a primary epigenetic
      modification that is involved in major processes such as cancer, genomic
      imprinting, gene silencing, etc. The significance of CpG island methylation
      status in normal development, cell differentiation and gene expression is widely
      recognized, although still stays poorly understood. METHODS: We performed whole
      genome DNA methylation array analysis on DNA pool samples from peripheral blood
      from 159 affected individuals and 170 healthy individuals. This technique allowed
      us to determine the methylation status of 27 627 CpG islands throughout the whole
      genome in healthy controls and BEN patients. Thus we obtained the methylation
      profile of BEN patients from Bulgarian and Serbian endemic regions. RESULTS:
      Using specifically developed software we compared the methylation profiles of BEN
      patients and corresponding controls and revealed the differently methylated
      regions. We then compared the DMRs between all patient-control pairs to determine
      common changes in the epigenetic profiles.SEC61G, IL17RA, HDAC11 proved to be
      differently methylated throughout all patient-control pairs. The CpG islands of
      all 3 genes were hypomethylated compared to controls. This suggests that
      dysregulation of these genes involved in immunological response could be a common
      mechanism in BEN pathogenesis in both endemic regions and in both genders.
      CONCLUSION: Our data propose a new hypothesis that immunologic dysregulation has
      a place in BEN etiopathogenesis.

PMID- 24131582
TI  - Autosomal recessive axonal neuropathy with neuromyotonia: a rare entity.
AB  - BACKGROUND: Autosomal recessive axonal neuropathy with neuromyotonia is a
      recently described entity associated to the HINT1 gene, encoding histidine triad
      nucleotide-binding protein 1. PATIENT: The authors report a Portuguese 16-year
      old girl of Roma ethnicity, descendant of consanguineous parents, with
      progressive distal muscular atrophy and weakness, beginning at age 6. After
      several years of extensive investigation with inconclusive results, clinical
      myotonia was identified. Electrophysiologic studies revealed neuromyotonia
      associated with a severe chronic predominantly motor axonal neuropathy and
      homozygous mutation (c.334 C > A, p.H112 N) in HINT1 was detected. CONCLUSION:
      This report emphasizes the late onset of clinical myotonia essential to the
      diagnosis.

PMID- 24131583
TI  - Neuromyelitis optica with onset in childhood and adolescence.
AB  - BACKGROUND: Neuromyelitis optica with onset before the age of 18 years is a
      relatively rare, yet potentially devastating condition. The objective of the
      present study was to contribute to the study of early-onset neuromyelitis optica
      with a case series. PATIENTS: Data were collected from medical records of
      Brazilian neurologists caring for patients with neuromyelitis optica occurring in
      childhood and adolescence. RESULTS: Twenty-nine patients with neuromyelitis
      optica occurring before the age of 18 years and fulfilling the diagnostic
      criteria were identified. The average age at disease onset was 13 years and the
      patients had had an average disease duration of 6 years. The expanded disability
      scale score at the latest consultation was, on average, 4.7, and one patient had
      died from the disease. The 29 patients had had an average 4.5 relapses during the
      disease, accounting for 0.75 relapses per year, irrespective of the medication
      used. All patients were using one or more of the following medications:
      azathioprine, prednisone, immunoglobulin, and glatiramer acetate. CONCLUSIONS:
      Neuromyelitis optica with onset in childhood and adolescence is a poorly
      understood condition that is often disabling and difficult to manage.

PMID- 24131584
TI  - Prevalence and comparison of Streptococcus infantarius subsp. infantarius and
      Streptococcus gallolyticus subsp. macedonicus in raw and fermented dairy products
      from East and West Africa.
AB  - Streptococcus infantarius subsp. infantarius (Sii) and Streptococcus gallolyticus
      subsp. macedonicus are members of the Streptococcus bovis/Streptococcus equinus
      complex (SBSEC) associated with human infections. SBSEC-related endocarditis was
      furthermore associated with rural residency in Southern Europe. SBSEC members are
      increasingly isolated as predominant species from fermented dairy products in
      Europe, Asia and Africa. African variants of Sii displayed dairy adaptations to
      lactose metabolism paralleling those of Streptococcus thermophilus including
      genome decay. In this study, the aim was to assess the prevalence of Sii and
      possibly other SBSEC members in dairy products of East and West Africa in order
      to identify their habitat, estimate their importance in dairy fermentation
      processes and determine geographic areas affected by this potential health risk.
      Presumptive SBSEC members were isolated on semi-selective M17 and SM agar media.
      Subsequent genotypic identification of isolates was based on rep-PCR
      fingerprinting and SBSEC-specific16S rRNA gene PCR assay. Detailed identification
      was achieved through application of novel primers enhancing the binding
      stringency in partial groES/groEL gene amplification and subsequent DNA
      sequencing. The presence of S. thermophilus-like lacS and lacZ genes in the SBSEC
      isolates was determined to elucidate the prevalence of this dairy adaptation.
      Isolates (n = 754) were obtained from 72 raw and 95 fermented milk samples from
      Cote d'Ivoire and Kenya on semi-selective agar media. Colonies of Sii were not
      detected from raw milk despite high microbial titers of approximately 10(6)CFU/mL
      on M17 agar medium. However, after spontaneous milk fermentation Sii was
      genotypically identified in 94.1% of Kenyan samples and 60.8% of Kenyan isolates.
      Sii prevalence in Cote d'Ivoire displayed seasonal variations in samples from
      32.3% (June) to 40.0% (Dec/Jan) and isolates from 20.5% (June) to 27.7% (Dec/Jan)
      present at titers of 10(6)-10(8)CFU/mL. lacS and lacZ genes were detected in all
      Kenyan and 25.8% (June) to 65.4% (Dec/Jan) of Ivorian Sii isolates. Regional
      differences in prevalence of Sii and dairy adaptations were observed, but no
      clear effect of dairy animal, fermentation procedure and climate was revealed.
      Conclusively, the high prevalence of Sii in Kenya, Cote d'Ivoire in addition to
      Somalia, Sudan and Mali strongly indicates a pivotal role of Sii in traditional
      African dairy fermentations potentially paralleling that of typical western dairy
      species S. thermophilus. Putative health risks associated with the consumption of
      high amounts of live Sii and potential different degrees of evolutionary
      adaptation or ecological colonization require further epidemiologic and genomic
      investigations, particularly in Africa.

PMID- 24131585
TI  - [Monitoring of viral pathogens in pediatric intensive care unit and analysis of
      clinical significance].
AB  - OBJECTIVE: To study the characteristics of viral spectrum and clinical features
      of children in pediatric intensive care unit (PICU). METHOD: Nasopharyngeal
      aspirate specimens (NPA) from 349 patients(1 from each) and 130 cerebrospinal
      fluids (CSF) specimens were collected from children who were admitted to the PICU
      of Second Affiliated Hospital of Shantou University Medical College. Additional
      87 NPA specimens were collected from healthy children for routine examination on
      the physical examination center, and the clinical data were collected. Multiplex
      PCR was applied to detect 16 kinds of viruses from NPA and CSF. Fluorescence
      quantitative PCR was applied to detect 13 viruses from CSF and to analyze the
      clinical data of positive cases. RESULT: There were 209 samples (59.9%) of the
      349 NPA specimens were positive for viruses, which included 117 cases positive
      for human rhinovirus (HRV), 60 for respiratory syncytial virus (RSV), 20 for
      influenza virus A (Inf A), 10 for adenovirus (ADV), 6 for parainfluenza virus
      type 3(PIV-3), 6 for human Boca virus (HBoV), 5 for influenza virus C(Inf C), 4
      for parainfluenza virus type 4(PIV-4), 4 for human coronavirus-HKU1/OC43, 3 for
      influenza virus B (Inf B), 3 for WU Polyomavirus (WUPyV), 2 parainfluenza virus
      type 1(PIV-1), 2 human metapneumovirus (HMPV) and 1 human coronavirus-NL63/229E.
      But none from 87 healthy controls were positive for any respiratory virus. Among
      the 130 CSF specimens, in 58 cases the diagnosis was viral encephalitis. There
      were 22 samples (37.9%) among the 58 CSF specimens positive for viruses, which
      included 14 enterovirus (EV), 3 human cytomegalovirus (HCMV), 2 mumps virus, 1
      coxsackie virus A16 (Cox-A16), 1 herpes simplex virus (HSV) and 1 human
      rhinovirus (HRV). The total positive rate was 63.3% (221/349) . Co-infection by
      at least 2 viral pathogens under study was observed in 45 of the 349 patients
      (12.9% of the total number of cases, 20.4% of the positives cases). The commonest
      pathogens in co-infected samples were WUPyV (100%) and HMPV(100%). The positive
      rate of virus peaked in the first 6 months of life, the rate in boys were higher
      than in girls and the peak season was summer. The numbers of none serious cases
      in the virus positive group were less than those in the virus negative group
      while the numbers of extremely serious cases in the virus positive group were
      higher than in the virus negative group. CONCLUSION: Viral pathogen is a major
      cause of infectious disease in pediatric critical illnesses and virus infection
      may lead to severe illness.

PMID- 24131586
TI  - Wnt inhibitory factor (WIF)-1 promotes melanogenesis in normal human melanocytes.
AB  - Wnt signaling plays a role in the differentiation as well as the development of
      melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma
      expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with
      perilesional normal skin. In this study, the expression and functional roles of
      WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the
      melanocytes of normal human skin and in cultured melanocytes. The upregulation of
      WIF-1 on cultured normal human melanocytes significantly induced expressions of
      MITF and tyrosinase, which were associated with increased melanin content and
      tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA
      reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in
      melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ
      cultured human skin. These findings suggest that melanocytes express WIF-1
      constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in
      normal human melanocytes. 

PMID- 24131587
TI  - The Children and Parents in Focus project: a population-based cluster-randomised
      controlled trial to prevent behavioural and emotional problems in children.
AB  - BACKGROUND: There is large body of knowledge to support the importance of early
      interventions to improve child health and development. Nonetheless, it is
      important to identify cost-effective blends of preventive interventions with
      adequate coverage and feasible delivery modes. The aim of the Children and
      Parents in Focus trial is to compare two levels of parenting programme intensity
      and rate of exposure, with a control condition to address impact and cost
      effectiveness of a universally offered evidence-based parenting programme in the
      Swedish context. METHODS/DESIGN: The trial has a cluster randomised controlled
      design comprising three arms: Universal arm (with access to participation in
      Triple P - Positive Parenting Program, level 2); Universal Plus arm (with access
      to participation in Triple P - Positive Parenting Program, level 2 as well as
      level 3, and level 4 group); and Services as Usual arm. The sampling frame is
      Uppsala municipality in Sweden. Child health centres consecutively recruit
      parents of children aged 3 to 5 years before their yearly check-ups (during the
      years 2013-2017). Outcomes will be measured annually. The primary outcome will be
      children's behavioural and emotional problems as rated by three informants:
      fathers, mothers and preschool teachers. The other outcomes will be parents'
      behaviour and parents' general health. Health economic evaluations will analyse
      cost-effectiveness of the interventions versus care as usual by comparing the
      costs and consequences in terms of impact on children's mental health, parent's
      mental health and health-related quality of life. DISCUSSION: This study
      addresses the need for comprehensive evaluation of the long-term effects, costs
      and benefits of early parenting interventions embedded within existing systems.
      In addition, the study will generate population-based data on the mental health
      and well-being of preschool aged children in Sweden. TRIAL REGISTRATION ISRCTN:
      ISRCTN16513449.

PMID- 24131588
TI  - Perihospitalization patterns of hemoglobin levels and erythropoiesis-stimulating
      agent doses in US hemodialysis patients, 1998-2009.
AB  - Anemia management in hemodialysis patients is of primary importance for
      clinicians and dialysis providers. Through a retrospective claims analysis, we
      studied prevalent US hemodialysis patients 1998-2009, and examined patterns of
      hemoglobin levels and erythropoiesis-stimulating agent (ESA, epoetin [EPO], and
      darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient
      claims were used to determine monthly ESA doses and associated hemoglobin levels.
      ESA dose trajectories were defined with repeated measures models incorporating an
      autoregressive covariance matrix that compared subsequent measurements with the
      index month of hospitalization, with variance component covariance matrices
      chosen for pair-wise comparisons. Regarding prehospitalization hemoglobin levels,
      a biphasic pattern occurred in both the EPO (1998-2009, n = 161,242) and DPO
      (2004-2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter
      in the EPO population, and fell after 2006 or 2007 in the DPO population. In the
      EPO population, the proportions of patients with hemoglobin less than 10 g/dL
      were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for
      the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of
      year-to-year variability occurred, EPO dose trends were less pronounced, with an
      apparent peak in 2004 followed by a modest decline; trends were similar for DPO.
      Trends in EPO dose trajectories did not completely parallel those for hemoglobin
      level; while EPO doses increased yearly up to 2004, doses stabilized, but did not
      materially decrease after 2004. No definite annual trends for DPO dose
      trajectories were apparent. 

PMID- 24131589
TI  - Prevalence of cutaneous adverse events associated with long-term disease
      modifying therapy and their impact on health-related quality of life in patients
      with multiple sclerosis: a cross-sectional study.
AB  - BACKGROUND: Glatiramer acetate (GA) and interferon-beta (IFN-beta) are disease
      modifying therapies (DMTs) for multiple sclerosis that are administered through
      subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated
      with DMTs are common and may influence patient's health-related quality of life
      (QoL). We aimed to determine the prevalence of cutaneous adverse events
      associated with long-term DMT use, and to assess the impact of cutaneous adverse
      events on QoL. METHODS: A cross-sectional study among patients with multiple
      sclerosis who had been treated with their first DMT for at least 2 years.
      Cutaneous events were assessed from photographs of injection-sites by
      dermatologists blinded for DMT. Generic and dermatology-specific health-related
      QoL were assessed using validated patient-reported questionnaires. RESULTS: A
      total of 229 patients were enrolled, of whom 156 (68%) had at least one skin
      reaction. The prevalence of cutaneous adverse events was higher for SC DMTs (75
      82%) compared to IM DMT (41%) (P < 0.001). Erythema and lipoatrophy were the most
      common skin reactions, observed in 156 (68%) and 45 (20%) patients, respectively.
      Dermatology-specific, but not generic, QoL was significantly lower among patients
      with skin reactions compared to those without. CONCLUSIONS: The prevalence of
      cutaneous adverse events was high in long-term DMT-treatment. Patients with
      cutaneous adverse events had a lower perceived dermatology-specific QoL.

PMID- 24131590
TI  - The Y2 receptor agonist PYY(3-36) increases the behavioural response to novelty
      and acute dopaminergic drug challenge in mice.
AB  - The gastrointestinal hormone PYY(3-36) is a preferential Y2 neuropeptide Y (NPY)
      receptor agonist. Recent evidence indicates that PYY(3-36) acts on central
      dopaminergic pathways, but its influence on dopamine-dependent behaviours remains
      largely unknown. We therefore explored the effects of peripheral PYY(3-36)
      treatment on the behavioural responses to novelty and to dopamine-activating
      drugs in mice. In addition, we examined whether PYY(3-36) administration may
      activate distinct dopamine and gamma-aminobutyric acid (GABA) cell populations in
      the mesoaccumbal and nigrostriatal pathways. We found that i.p. PYY(3-36)
      injection led to a dose-dependent increase in novel object exploration. The
      effective dose of PYY(3-36) (1 MUg/100 g body weight) also potentiated the
      locomotor reaction to the indirect dopamine receptor agonist amphetamine and
      increased stereotyped climbing/leaning responses following administration of the
      direct dopamine receptor agonist apomorphine. PYY(3-36) administration did not
      affect activity of midbrain dopaminergic cells as evaluated by double immuno
      enzyme staining of the neuronal early gene product c-Fos with tyrosine
      hydroxylase. PYY(3-36) did, however, lead to a marked increase in the number of
      cells co-expressing c-Fos with glutamic acid decarboxylase in the nucleus
      accumbens and caudate putamen, indicating activation of GABAergic cells in dorsal
      and ventral striatal areas. Our results support the hypothesis that acute
      administration of the preferential Y2 receptor agonist PYY(3-36) modulates
      dopamine-dependent behaviours. These effects do not seem to involve direct
      activation of midbrain dopamine cells but instead are associated with neuronal
      activation in the major input areas of the mesoaccumbal and nigrostriatal
      pathways.

PMID- 24131591
TI  - Impact of breast cancer subtypes on 3-year survival among adolescent and young
      adult women.
AB  - INTRODUCTION: Young women have poorer survival after breast cancer than do older
      women. It is unclear whether this survival difference relates to the unique
      distribution of hormone receptor (HR) and human epidermal growth factor receptor
      2 (HER2)-defined molecular breast cancer subtypes among adolescent and young
      adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine
      associations between breast cancer subtypes and short-term survival in AYA women,
      as well as to determine whether the distinct molecular subtype distribution among
      AYA women explains the unfavorable overall breast cancer survival statistics
      reported for AYA women compared with older women. METHODS: Data for 5,331 AYA
      breast cancers diagnosed between 2005 and 2009 were obtained from the California
      Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR
      /HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox
      proportional hazards regression with follow-up through 2010. RESULTS: With up to
      6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA
      women diagnosed with HR-/HER + and triple-negative breast cancer experienced a
      1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR
      /HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple
      negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard
      ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI,
      1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided
      in lower socioeconomic status neighborhoods, had public health insurance, and
      were of Black, compared with White, race/ethnicity experienced worse survival.
      This race/ethnicity association was attenuated somewhat after adjusting for
      breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had
      similar all-cause and breast cancer-specific short-term survival as older women
      for all breast cancer subtypes and across all stages of disease. CONCLUSIONS:
      Among AYA women with breast cancer, short-term survival varied by breast cancer
      subtypes, with the distribution of breast cancer subtypes explaining some of the
      poorer survival observed among Black, compared with White, AYA women. Future
      studies should consider whether distribution of breast cancer subtypes and other
      factors, including differential receipt of treatment regimens, influences long
      term survival in young compared with older women.

PMID- 24131592
TI  - Damage to the anterior arcuate fasciculus predicts non-fluent speech production
      in aphasia.
AB  - Non-fluent aphasia implies a relatively straightforward neurological condition
      characterized by limited speech output. However, it is an umbrella term for
      different underlying impairments affecting speech production. Several studies
      have sought the critical lesion location that gives rise to non-fluent aphasia.
      The results have been mixed but typically implicate anterior cortical regions
      such as Broca's area, the left anterior insula, and deep white matter regions. To
      provide a clearer picture of cortical damage in non-fluent aphasia, the current
      study examined brain damage that negatively influences speech fluency in patients
      with aphasia. It controlled for some basic speech and language comprehension
      factors in order to better isolate the contribution of different mechanisms to
      fluency, or its lack. Cortical damage was related to overall speech fluency, as
      estimated by clinical judgements using the Western Aphasia Battery speech fluency
      scale, diadochokinetic rate, rudimentary auditory language comprehension, and
      executive functioning (scores on a matrix reasoning test) in 64 patients with
      chronic left hemisphere stroke. A region of interest analysis that included brain
      regions typically implicated in speech and language processing revealed that non
      fluency in aphasia is primarily predicted by damage to the anterior segment of
      the left arcuate fasciculus. An improved prediction model also included the left
      uncinate fasciculus, a white matter tract connecting the middle and anterior
      temporal lobe with frontal lobe regions, including the pars triangularis. Models
      that controlled for diadochokinetic rate, picture-word recognition, or executive
      functioning also revealed a strong relationship between anterior segment
      involvement and speech fluency. Whole brain analyses corroborated the findings
      from the region of interest analyses. An additional exploratory analysis revealed
      that involvement of the uncinate fasciculus adjudicated between Broca's and
      global aphasia, the two most common kinds of non-fluent aphasia. In summary, the
      current results suggest that the anterior segment of the left arcuate fasciculus,
      a white matter tract that lies deep to posterior portions of Broca's area and the
      sensory-motor cortex, is a robust predictor of impaired speech fluency in aphasic
      patients, even when motor speech, lexical processing, and executive functioning
      are included as co-factors. Simply put, damage to those regions results in non
      fluent aphasic speech; when they are undamaged, fluent aphasias result. 

PMID- 24131594
TI  - The expanding spectrum of aetiologies causing retinal microcystic macular change.

PMID- 24131593
TI  - Neural network connectivity differences in children who stutter.
AB  - Affecting 1% of the general population, stuttering impairs the normally
      effortless process of speech production, which requires precise coordination of
      sequential movement occurring among the articulatory, respiratory, and resonance
      systems, all within millisecond time scales. Those afflicted experience frequent
      disfluencies during ongoing speech, often leading to negative psychosocial
      consequences. The aetiology of stuttering remains unclear; compared to other
      neurodevelopmental disorders, few studies to date have examined the neural bases
      of childhood stuttering. Here we report, for the first time, results from
      functional (resting state functional magnetic resonance imaging) and structural
      connectivity analyses (probabilistic tractography) of multimodal neuroimaging
      data examining neural networks in children who stutter. We examined how
      synchronized brain activity occurring among brain areas associated with speech
      production, and white matter tracts that interconnect them, differ in young
      children who stutter (aged 3-9 years) compared with age-matched peers. Results
      showed that children who stutter have attenuated connectivity in neural networks
      that support timing of self-paced movement control. The results suggest that
      auditory-motor and basal ganglia-thalamocortical networks develop differently in
      stuttering children, which may in turn affect speech planning and execution
      processes needed to achieve fluent speech motor control. These results provide
      important initial evidence of neurological differences in the early phases of
      symptom onset in children who stutter. 

PMID- 24131595
TI  - A new generation of trade policy: potential risks to diet-related health from the
      trans pacific partnership agreement.
AB  - Trade poses risks and opportunities to public health nutrition. This paper
      discusses the potential food-related public health risks of a radical new kind of
      trade agreement: the Trans Pacific Partnership agreement (TPP). Under negotiation
      since 2010, the TPP involves Australia, Brunei, Canada, Chile, Japan, Malaysia,
      Mexico, New Zealand, Peru, Singapore, the USA, and Vietnam. Here, we review the
      international evidence on the relationships between trade agreements and diet
      related health and, where available, documents and leaked text from the TPP
      negotiations. Similar to other recent bilateral or regional trade agreements, we
      find that the TPP would propose tariffs reductions, foreign investment
      liberalisation and intellectual property protection that extend beyond provisions
      in the multilateral World Trade Organization agreements. The TPP is also likely
      to include strong investor protections, introducing major changes to domestic
      regulatory regimes to enable greater industry involvement in policy making and
      new avenues for appeal. Transnational food corporations would be able to sue
      governments if they try to introduce health policies that food companies claim
      violate their privileges in the TPP; even the potential threat of litigation
      could greatly curb governments' ability to protect public health. Hence, we find
      that the TPP, emblematic of a new generation of 21st century trade policy, could
      potentially yield greater risks to health than prior trade agreements. Because
      the text of the TPP is secret until the countries involved commit to the
      agreement, it is essential for public health concerns to be articulated during
      the negotiation process. Unless the potential health consequences of each part of
      the text are fully examined and taken into account, and binding language is
      incorporated in the TPP to safeguard regulatory policy space for health, the TPP
      could be detrimental to public health nutrition. Health advocates and health
      related policymakers must be proactive in their engagement with the trade
      negotiations. 

PMID- 24131596
TI  - Secretome diversity and quantitative analysis of cellulolytic Aspergillus
      fumigatus Z5 in the presence of different carbon sources.
AB  - BACKGROUND: Aspergillus fumigatus Z5 has a strong ability to decompose
      lignocellulose biomass, and its extracellular protein secretion has been reported
      in earlier studies employing traditional techniques. However, a comprehensive
      analysis of its secretion in the presence of different carbon sources is still
      lacking. The goal of this work was to identify, quantify and compare the
      secretome of A. fumigatus Z5 in the presence of different carbon sources to
      understand in more details the mechanisms of lignocellulose decomposition by
      Aspergillus fumigatus Z5. RESULTS: Cellulolytic A. fumigatus Z5 was grown in the
      presence of glucose (Gl), Avicel (Av) and rice straw (RS), and the activities of
      several lignocellulosic enzymes were determined with chromatometry method. The
      maximum activities of endoglucanase, exoglucanase, beta-glucosidase,
      laminarinase, lichenase, xylanase and pectin lyase were 12.52, 0.59, 2.30, 2.37,
      1.68, 15.02 and 11.40 U.ml-1, respectively. A total of 152, 125 and 61 different
      proteins were identified in the presence of RS, Av and Gl, respectively, and the
      proteins were functionally divided into glycoside hydrolases, lipases,
      peptidases, peroxidases, esterases, protein translocating transporters and
      hypothetical proteins. A total of 49 proteins were iTRAQ-quantified in all the
      treatments, and the quantification results indicated that most of the cellulases,
      hemicellulases and glycoside hydrolases were highly upregulated when rice straw
      and Avicel were used as carbon sources (compared with glucose). CONCLUSIONS: The
      proteins secreted from A. fumigatus Z5 in the present of different carbon source
      conditions were identified by LC-MS/MS and quantified by iTRAQ-based quantitative
      proteomics. The results indicated that A. fumigatus Z5 could produce considerable
      cellulose-, hemicellulose-, pectin- and lignin-degrading enzymes that are
      valuable for the lignocellulosic bioenergy industry.

PMID- 24131598
TI  - Optimal plane for nerve sparing total mesorectal excision, immunohistological
      study and 3D reconstruction: an embryological study.
AB  - AIM: Genito-urinary complications are frequent after rectal surgery and are often
      due to nerve damage. The relationship between the pelvic nerves and surgical
      planes are unclear. The aim of the study was to determine the relationship
      between the inferior hypogastric plexus and the fascia of the lateral pelvic wall
      and between Denonvilliers' fascia and the efferent branches of the inferior
      hypogastric plexus. METHOD: Computer-assisted anatomical dissection was used.
      Serial histological sections were made from six human foetuses and a male adult.
      Sections were stained with haematoxylin and eosin, Masson's trichrome and
      immunostainings. The sections were then digitalized and reconstructed in three
      dimensions. RESULTS: The inferior hypogastric plexus was situated in a virtual
      space between the fascia propria of the rectum and the fascia on the upper
      surface of the levator ani. During the lateral dissection, the optimal surgical
      plane is the plane of the fascia propria of the rectum. We located Denonvilliers'
      fascia in three dimensions. It plays the role of a protective sheet for the
      neurovascular bundle. The optimal plane for nerve preservation is situated behind
      Denonvilliers' fascia. CONCLUSION: This study has enabled a clear visualization
      of the optimal planes to perform total mesorectal excision while ensuring nerve
      preservation. Three-dimensional visualization clearly helps to bridge the gap
      between histological examination and the findings of surgery.

PMID- 24131597
TI  - Antitumor and anti-cachectic effects of shark liver oil and fish oil: comparison
      between independent or associative chronic supplementation in Walker 256 tumor
      bearing rats.
AB  - BACKGROUND: Shark liver oil (SLOil) and fish oil (FOil), which are respectively
      rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are
      able to reduce the growth of some tumors and the burden of cachexia. It is known
      that FOil is able to reduce proliferation rate and increase apoptotic cells and
      lipid peroxidation of tumor cells efficiently. However, there are few reports
      revealing the influence of SLOil on these parameters. In the current study,
      effects of FOil chronic supplementation on tumor growth and cachexia were taken
      as reference to compare the results obtained with SLOil supplementation. Also, we
      evaluated if the association of SLOil and FOil was able to promote additive
      effects. METHODS: Weanling male Wistar rats were divided into 4 groups: fed
      regular chow (C), supplemented (1 g/kg body weight) with SLOil (CSLO), FOil (CFO)
      and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker
      256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical
      parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate
      and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG
      composition of tumor and oils were obtained by high performance liquid
      chromatography and gas chromatography - mass spectrometry, respectively.
      Statistical analysis was performed by unpaired t-test and one-way ANOVA followed
      by a post hoc Tukey test. RESULTS: Fourteen days after inoculation, SLOil was
      able to restore cachexia parameters to control levels, similarly to FOil. WSLO
      rats presented significantly lower tumor weight (40%), greater tumor cell
      apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor
      content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed
      more potent effects. Supplementation with SLOil + FOil did not promote additive
      effects. Additionally, chromatographic results suggested a potential
      incorporation competition between the n-3 fatty acids and the AKGs in the tumor
      cells' membranes. CONCLUSIONS: SLOil is another marine source of lipids with
      similar FOil anti-cachectic capacity. Furthermore, despite being less potent than
      FOil, SLOil presented significant in vivo antitumor effects. These results
      suggest that the chronic supplementation with SLOil may be adjuvant of the anti
      cancer therapy.

PMID- 24131599
TI  - Australian and New Zealand national evidence-based recommendations for the
      investigation and follow-up of undifferentiated peripheral inflammatory
      arthritis: an integration of systematic literature research and rheumatological
      expert opinion.
AB  - AIM: To develop Australian and New Zealand (ANZ) recommendations for the
      investigation and follow-up of undifferentiated peripheral inflammatory arthritis
      (UPIA) using an evidence-based approach. METHODS: Ten questions pertaining to the
      investigation and follow-up of patients with UPIA in daily rheumatological
      practice were defined by clinicians using a modified Delphi approach. A
      systematic literature search was conducted for each of the final questions. The
      results were presented to a workshop of 54 ANZ rheumatologists in May 2009.
      Discussions were held to develop consensus statements for each question, based on
      published evidence and clinical experience/expertise. RESULTS: Ten
      recommendations were made on diagnostic value of clinical features in the
      patient's history and examination, predictors of poor prognosis and persistence,
      synovial fluid analysis, serology, imaging and human leukocyte antigen B27
      testing. The lack of specific research to inform recommendations presented a
      challenge. Dynamic discussion groups outlined individual experience in areas
      without good quality clinical trial evidence. The median strength of support for
      the final set of recommendations was 7/10 (interquartile range 6-8), ranging from
      6 to 9 for individual statements. CONCLUSION: Ten ANZ recommendations for the
      investigation and follow-up of UPIA were formulated, based on available evidence
      and extensive clinical experience. The systematic literature review was of
      limited value while animated discussion of individual experience, with subsequent
      information exchange, highlighted the importance of merging clinical expertise
      with published literature to establish practical recommendations that can improve
      quality of care in rheumatology.

PMID- 24131600
TI  - Keep your friends close and your spouse closer.

PMID- 24131601
TI  - The effects of noise reduction technologies on the acceptance of background
      noise.
AB  - BACKGROUND: Directional microphones (D-Mics) and digital noise reduction (DNR)
      algorithms are used in hearing aids to reduce the negative effects of background
      noise on performance. Directional microphones attenuate sounds arriving from
      anywhere other than the front of the listener while DNR attenuates sounds with
      physical characteristics of noise. Although both noise reduction technologies are
      currently available in hearing aids, it is unclear if the use of these
      technologies in isolation or together affects acceptance of noise and/or
      preference for the end user when used in various types of background noise.
      PURPOSE: The purpose of the research was to determine the effects of D-Mic, DNR,
      or the combination of D-Mic and DNR on acceptance of noise and preference when
      listening in various types of background noise. RESEARCH DESIGN: An experimental
      study in which subjects were exposed to a repeated measures design was utilized.
      STUDY SAMPLE: Thirty adult listeners with mild sloping to moderately severe
      sensorineural hearing loss participated (mean age 67 yr). DATA COLLECTION AND
      ANALYSIS: Acceptable noise levels (ANLs) were obtained using no noise reduction
      technologies, D-Mic only, DNR only, and the combination of the two technologies
      (Combo) for three different background noises (single-talker speech, speech
      shaped noise, and multitalker babble) for each listener. In addition, preference
      rankings of the noise reduction technologies were obtained within each background
      noise (1 = best, 3 = worst). RESULTS: ANL values were significantly better for
      each noise reduction technology than baseline; and benefit increased
      significantly from DNR to D-Mic to Combo. Listeners with higher (worse) baseline
      ANLs received more benefit from noise reduction technologies than listeners with
      lower (better) baseline ANLs. Neither ANL values nor ANL benefit values were
      significantly affected by background noise type; however, ANL benefit with D-Mic
      and Combo was similar when speech-like noise was present while ANL benefit was
      greatest for Combo when speech spectrum noise was present. Listeners preferred
      the hearing aid settings that resulted in the best ANL value. CONCLUSION: Noise
      reduction technologies improved ANL for each noise type, and the amount of
      improvement was related to the baseline ANL value. Improving an ANL with noise
      reduction technologies is noticeable to listeners, at least when examined in this
      laboratory setting, and listeners prefer noise reduction technologies that
      improved their ability to accept noise.

PMID- 24131602
TI  - Differences in sensation level between the Widex Soundtracker and two real-ear
      analyzers.
AB  - BACKGROUND: SoundTracker is an algorithm in Widex's Compass fitting software that
      could potentially be used to estimate a patient's aided sensation level (SL).
      SoundTracker's accuracy of estimating a patient's SL has never been verified in
      comparison to SL measured with commercially available real-ear analyzers.
      PURPOSE: Determine whether statistically significant differences are present
      between the estimated SL of the Widex SoundTracker software application and the
      measured SL of the Audioscan Verifit and Frye 6500 real-ear analyzers at 500,
      1000, 2000, and 4000 Hz. RESEARCH DESIGN: This study used a randomized repeated
      measures design to determine differences in SL between SoundTracker and the
      Verifit and 6500. STUDY SAMPLE: Ten subjects (N = 20 ears) were recruited who
      were experienced users of behind-the-ear hearing aids with conventional vented
      earmolds and had bilateral sensorineural hearing loss that was >30 dB HL below
      1000 Hz and <=70 dB HL to 4000 Hz. DATA COLLECTION AND ANALYSIS: Real-ear in-situ
      thresholds (dB sound pressure level [SPL]) and real-ear aided responses (REAR; dB
      SPL) were measured at 500, 1000, 2000, and 4000 Hz to determine differences in SL
      between SoundTracker, Verifit, and 6500. A three-factor repeated measures
      analysis of variance (ANOVA) was utilized to determine differences between method
      (real-ear analyzers and SoundTracker), analyzer (Verifit and 6500), and frequency
      (500, 1000, 2000, and 4000 Hz). RESULTS: Mean differences in measured SL for the
      Verifit and 6500 were <=2 dB when compared to the estimated SL using
      SoundTracker. A statistically significant difference in SL was present between
      the Verifit and SoundTracker at 2000 Hz (p < 0.01), but no significant
      differences were present at 500, 1000, and 4000 Hz. A statistically significant
      difference in SL was present between the 6500 and SoundTracker at 4000 Hz (p <
      0.01), but no significant differences were present at 500, 1000, and 2000 Hz.
      Mean differences in measured SL between the real-ear analyzers (difference of
      SoundTracker SL minus Verifit SL compared to the difference of SoundTracker SL
      minus 6500 SL) were <=2 dB with a statistically significant difference present at
      2000 Hz (p < 0.01), but no statistically significant differences were present at
      500, 1000, or 4000 Hz. CONCLUSIONS: Nearly 85% of the differences between the
      estimated SoundTracker SL and the measured SLs of the Verifit and 6500 were <=2
      dB. Despite some limitations of this study, SoundTracker could be useful as a
      counseling tool to illustrate to patients which sounds are audible or inaudible
      when unaided and aided.

PMID- 24131603
TI  - Measuring the long-term SNRs of static and adaptive compression amplification
      techniques for speech in noise.
AB  - BACKGROUND: Multichannel wide-dynamic-range compression (WDRC) is a widely
      adopted amplification scheme in modern digital hearing aids. It attempts to
      provide individuals with loudness recruitment with superior speech
      intelligibility and greater listening comfort over a wider range of input levels.
      However, recent surveys have shown that compression processing (operating in the
      nonlinear regime) usually reduces the long-term signal-to-noise ratio (SNR).
      PURPOSE: The purpose of this study was to determine the long-term SNR in an
      adaptive compression-ratio (CR) amplification scheme called adaptive wide-dynamic
      range compression (AWDRC), and to determine whether this concept is better than
      static WDRC amplification at improving the long-term SNR for speech in noise.
      DESIGN AND STUDY SAMPLE: AWDRC uses the input short-term dynamic range to adjust
      the CR to maximize audibility and comfort. Various methods for evaluating the
      long-term SNR were used to observe the relationship between the CR and output SNR
      performance in AWDRC for seven typical audiograms, and to compare the results
      with those for static WDRC amplification. RESULTS: The results showed that the
      variation of the CR in AWDRC amplification can maintain the comfort and
      audibility of the output sound. In addition, the average long-term SNR improved
      by 0.1-5.5 dB for a flat hearing loss, by 0.2-3.4 dB for a reverse sloping
      hearing loss, by 1.4-4.8 dB for a high-frequency hearing loss, and by 0.3-5.7 dB
      for a mild-to-moderate-sloping high-frequency hearing loss relative to static
      WDRC amplification. The output long-term SNR differed significantly (p < .001)
      between static WDRC and AWDRC amplification. CONCLUSIONS: The results of this
      study show that AWDRC, which uses the characteristics of the input signal to
      adaptively adjust the CR, provides better long-term SNR performance than static
      WDRC amplification.

PMID- 24131604
TI  - Dichotic assessment of verbal memory function: development and validation of the
      Persian version of Dichotic Verbal Memory Test.
AB  - BACKGROUND AND PURPOSE: The Dichotic Verbal Memory Test (DVMT) is useful in
      detecting verbal memory deficits and differences in memory function between the
      brain hemispheres. The purpose of this study was to prepare the Persian version
      of DVMT, to obtain its results in 18- to 25-yr-old Iranian individuals, and to
      examine the ear, gender, and serial position effect. RESEARCH DESIGN: The Persian
      version of DVMT consisted of 18 10-word lists. After preparing the 18 lists,
      content validity was assessed by a panel of eight experts and the equivalency of
      the lists was evaluated. Then the words were recorded on CD in a dichotic mode
      such that 10 words were presented to one ear, with the same words reversed
      simultaneously presented to the other ear. Thereafter, it was performed on a
      sample of young, normal, Iranian individuals. STUDY SAMPLE: Thirty normal
      individuals (no history of neurological, ontological, or psychological diseases)
      with ages ranging from 18 to 25 yr were examined for evaluating the equivalency
      of the lists, and 110 subjects within the same age range participated in the
      final stage of the study to obtain the normative data on the developed test.
      RESULTS: There was no significant difference between the mean scores of the 18
      developed lists (p > 0.05). The mean content validity index (CVI) score was .96.
      A significant difference was found between the mean score of the two ears (p <
      0.05) and between female and male participants (p < 0.05). CONCLUSION: The
      Persian version of DVMT has good content validity and can be used for verbal
      memory assessment in Iranian young adults.

PMID- 24131605
TI  - The advantage of knowing the talker.
AB  - BACKGROUND: Many audiologists have observed a situation where a patient appears
      to understand something spoken by his or her spouse or a close friend but not the
      same information spoken by a stranger. However, it is not clear whether this
      observation reflects choice of communication strategy or a true benefit derived
      from the talker's voice. PURPOSE: The current study measured the benefits of long
      term talker familiarity for older individuals with hearing impairment in a
      variety of listening situations. RESEARCH DESIGN: In Experiment 1, we measured
      speech recognition with familiar and unfamiliar voices when the difficulty level
      was manipulated by varying levels of a speech-shaped background noise. In
      Experiment 2, we measured the benefit of a familiar voice when the background
      noise was other speech (informational masking). STUDY SAMPLE: A group of 31 older
      listeners with high-frequency sensorineural hearing loss participated in the
      study. Fifteen of the participants served as talkers and 16 as listeners. In each
      case, the talker-listener pair for the familiar condition represented a close,
      long-term relationship (spouse or close friend). DATA COLLECTION AND ANALYSIS:
      Speech-recognition scores were compared using controlled stimuli (low-context
      sentences) recorded by the study talkers. The sentences were presented in quiet
      and in two levels of speech-spectrum noise (Experiment 1) as well as in
      multitalker babble (Experiment 2). Repeated-measures analysis of variance was
      used to compare performance between the familiar and unfamiliar talkers, within
      and across conditions. RESULTS: Listeners performed better when speech was
      produced by a talker familiar to them, whether that talker was in a quiet or
      noisy environment. The advantage of the familiar talker was greater in a more
      adverse listening situation (i.e., in the highest level of background noise) but
      was similar for speech-spectrum noise and multitalker babble. CONCLUSIONS: The
      present data support a frequent clinical observation: listeners can understand
      their spouse better than a stranger. This effect was present for all our
      participants and occurred under strictly controlled conditions in which the only
      possible cue was the voice itself, rather than under normal communicative
      conditions where listener accommodation strategies on the part of the talker may
      confound the measurable benefit. The magnitude of the effect was larger than
      shown for short-term familiarity in previous work. This suggests that older
      listeners with hearing loss who inherently operate under deficient auditory
      conditions can benefit from experience with the voice characteristics of a long
      term communication partner over many years of a relationship.

PMID- 24131606
TI  - The effectiveness of the directional microphone in the Oticon Medical Ponto Pro
      in participants with unilateral sensorineural hearing loss.
AB  - BACKGROUND: Current bone anchored hearing solutions (BAHSs) have incorporated
      automatic adaptive multichannel directional microphones (DMs). Previous fixed
      single-channel hypercardioid DMs in BAHSs have provided benefit in a diffuse
      listening environment, but little data are available on the performance of
      adaptive multichannel DMs in BAHSs for persons with unilateral sensorineural
      hearing loss (USNHL). PURPOSE: The primary goal was to determine if statistically
      significant differences existed in the mean Reception Threshold for Sentences
      (RTS in dB) in diffuse uncorrelated restaurant noise between unaided, an
      omnidirectional microphone (OM), split DM (SDM), and full DM (FDM) in the Oticon
      Medical Ponto Pro. A second goal was to assess subjective benefit using the
      Abbreviated Profile of Hearing Aid Benefit (APHAB) comparing the Ponto Pro to the
      participant's current BAHS, and the Ponto Pro and participant's own BAHS to
      unaided. The third goal was to compare RTS data of the Ponto Pro to data from an
      identical study examining Cochlear Americas' Divino. RESEARCH DESIGN: A
      randomized repeated measures, single blind design was used to measure an RTS for
      each participant for unaided, OM, SDM, and FDM. STUDY SAMPLE: Fifteen BAHS users
      with USNHL were recruited from Washington University in St. Louis and the
      surrounding area. DATA COLLECTION AND ANALYSIS: The Ponto Pro was fit by
      measuring in-situ bone conduction thresholds and was worn for 4 wk. An RTS was
      obtained utilizing Hearing in Noise Test (HINT) sentences in uncorrelated
      restaurant noise from an eight loudspeaker array, and subjective benefit was
      determined utilizing the APHAB. Analysis of variance (ANOVA) was used to analyze
      the results of the Ponto Pro HINT and APHAB data, and comparisons between the
      Ponto Pro and previous Divino data. RESULTS: No statistically significant
      differences existed in mean RTS between unaided, the Ponto Pro's OM, SDM, or FDM
      (p = 0.10). The Ponto Pro provided statistically significant benefit for the
      Background Noise (BN) (p < 0.01) and Reverberation (RV) (p < 0.05) subscales
      compared to the participant's own BAHS. The Ponto Pro (Ease of Communication [EC]
      [p < 0.01], BN [p < 0.001], and RV [p < 0.01] subscales) and participant's own
      BAHS (BN [p < 0.01] and RV [p < 0.01] subscales) overall provided statistically
      significant benefit compared to unaided. Clinically significant benefit of 5% was
      present for the Ponto Pro compared to the participant's own BAHS and 10% for the
      Ponto Pro and the participant's own BAHS compared to unaided. The Ponto Pro's OM
      (p = 0.05), SDM (p = 0.05), and FDM (p < 0.01) were statistically significantly
      better than the Divino's OM. No significant differences existed between the Ponto
      Pro's OM, SDM, and FDM compared to the Divino's DM. CONCLUSIONS: No statistically
      significant differences existed between unaided, OM, SDM, or FDM. Participants
      preferred the Ponto Pro compared to the participant's own BAHS and the Ponto Pro
      and participant's own BAHS compared to unaided. The RTS of the Ponto Pro's
      adaptive multichannel DM was similar to the Divino's fixed hypercardioid DM, but
      the Ponto Pro's OM was statistically significantly better than the Divino's OM.

PMID- 24131607
TI  - Evaluation of speech recognition of cochlear implant recipients using a personal
      digital adaptive radio frequency system.
AB  - BACKGROUND: Previous research supports the use of frequency modulation (FM)
      systems for improving speech recognition in noise of individuals with cochlear
      implants (CIs). However, at this time, there is no published research on the
      potential speech recognition benefit of new digital adaptive wireless radio
      transmission systems. PURPOSE: The goal of this study was to compare speech
      recognition in quiet and in noise of CI recipients while using traditional, fixed
      gain analog FM systems, adaptive analog FM systems, and adaptive digital wireless
      radio frequency transmission systems. RESEARCH DESIGN: A three-way repeated
      measures design was used to examine performance differences among devices, among
      speech recognition conditions in quiet and in increasing levels of background
      noise, and between users of Advanced Bionics and Cochlear CIs. STUDY SAMPLE:
      Seventeen users of Advanced Bionics Harmony CI sound processors and 20 users of
      Cochlear Nucleus 5 sound processors were included in the study. DATA COLLECTION
      AND ANALYSIS: Participants were tested in a total of 32 speech-recognition-in
      noise-test conditions, which included one no-FM and three device conditions
      (fixed-gain FM, adaptive FM, and adaptive digital) at the following signal
      levels: 64 dBA speech (at the location of the participant) in quiet and 64 dBA
      speech with competing noise at 50, 55, 60, 65, 70, 75, and 80 dBA noise levels.
      RESULTS: No significant differences were detected between the users of Advanced
      Bionics and Cochlear CIs. All of the radio frequency system conditions (i.e.,
      fixed-gain FM, adaptive FM, and adaptive digital) outperformed the no-FM
      conditions in test situations with competing noise. Specifically, in conditions
      with 70, 75, and 80 dBA of competing noise, the adaptive digital system provided
      better performance than the fixed-gain and adaptive FM systems. The adaptive FM
      system did provide better performance than the fixed-gain FM system at 70 and 75
      dBA of competing noise. At the lower noise levels of 50, 55, 60, and 65 dBA, no
      significant differences were detected across the three systems, and no
      significant differences were found across the quiet conditions. In all
      conditions, performance became poorer as the competing noise level increased.
      CONCLUSIONS: In high levels of noise, the adaptive digital system provides
      superior performance when compared to adaptive analog FM and fixed-gain FM
      systems.

PMID- 24131609
TI  - Simulated patients in audiology education: student reports.
AB  - BACKGROUND: Despite increased attention in recent years to audiology counseling
      education, students remain concerned about their abilities to interact with
      patients in challenging situations, such as when breaking difficult news.
      Simulated patients, or actors trained to portray patients in clinical scenarios,
      have been used for many years in medical schools to teach and assess students'
      interpersonal skills, and are just beginning to be used in audiology programs.
      Although research suggests that medical students value simulated patient
      experiences, little is known about whether the same is true for audiology
      students. PURPOSE: The purpose of this study was to survey audiology students who
      had completed a simulated patient counseling experience as part of their graduate
      coursework at Central Michigan University, to learn about their experiences and
      views of this instructional format. RESEARCH DESIGN: This study used descriptive
      and comparative statistics to report student observations and to determine if
      student responses to evaluative questions differed from chance. STUDY SAMPLE:
      Study participants included 29 audiology students who had completed a "breaking
      difficult news" simulated patient experience as part of their required graduate
      coursework in patient counseling. DATA COLLECTION AND ANALYSIS: Participants
      completed an online survey that included seven evaluative five-point Likert-scale
      questions about their simulated patient counseling experience. Participants also
      completed one multiple-choice question on suggestions for future simulated
      patient sessions. RESULTS: For each of the seven evaluative questions, a majority
      of participants (76-100%) responded positively, agreeing or strongly agreeing
      that the experience was helpful to their learning. For each of these evaluative
      questions, a chi2 analysis revealed that the distribution of positive (i.e.,
      strongly agree and agree) to nonpositive (i.e., neutral, disagree, and strongly
      disagree) responses differed significantly from chance (p < .0001, df = 1). The
      results also indicated that when asked which of several suggested clinical
      scenarios would be helpful for future sessions, simulations of challenging
      patient types (i.e., hostile, rambling, and noncommunicative patients) were
      supported by most (62-90%) respondents. CONCLUSIONS: The results of the present
      study are consistent with findings of medical students' positive perceptions of
      simulated patient experiences as well as those previously reported for audiology
      students. Together, these data support the continued use of simulated patients as
      a method of instruction for audiology counseling education for breaking difficult
      news, and suggest a potential value of using simulated patient interactions for
      training counseling skills in other clinical situations and scenarios.

PMID- 24131608
TI  - Extended high-frequency thresholds in college students: effects of music player
      use and other recreational noise.
AB  - BACKGROUND: Human hearing is sensitive to sounds from as low as 20 Hz to as high
      as 20,000 Hz in normal ears. However, clinical tests of human hearing rarely
      include extended high-frequency (EHF) threshold assessments, at frequencies
      extending beyond 8000 Hz. EHF thresholds have been suggested for use monitoring
      the earliest effects of noise on the inner ear, although the clinical usefulness
      of EHF threshold testing is not well established for this purpose. PURPOSE: The
      primary objective of this study was to determine if EHF thresholds in healthy,
      young adult college students vary as a function of recreational noise exposure.
      RESEARCH DESIGN: A retrospective analysis of a laboratory database was conducted;
      all participants with both EHF threshold testing and noise history data were
      included. The potential for "preclinical" EHF deficits was assessed based on the
      measured thresholds, with the noise surveys used to estimate recreational noise
      exposure. STUDY SAMPLE: EHF thresholds measured during participation in other
      ongoing studies were available from 87 participants (34 male and 53 female); all
      participants had hearing within normal clinical limits (<=25 HL) at conventional
      frequencies (0.25-8 kHz). RESULTS: EHF thresholds closely matched standard
      reference thresholds [ANSI S3.6 (1996) Annex C]. There were statistically
      reliable threshold differences in participants who used music players, with 3-6
      dB worse thresholds at the highest test frequencies (10-16 kHz) in participants
      who reported long-term use of music player devices (>5 yr), or higher listening
      levels during music player use. CONCLUSIONS: It should be possible to detect
      small changes in high-frequency hearing for patients or participants who undergo
      repeated testing at periodic intervals. However, the increased population-level
      variability in thresholds at the highest frequencies will make it difficult to
      identify the presence of small but potentially important deficits in otherwise
      normal-hearing individuals who do not have previously established baseline data.

PMID- 24131610
TI  - Role of hearing AIDS in tinnitus intervention: a scoping review.
AB  - BACKGROUND: Tinnitus can have a devastating impact on the quality of life of the
      sufferer. Although the mechanisms underpinning tinnitus remain uncertain, hearing
      loss is often associated with its onset, and hearing aids are among the most
      commonly used tools for its management. PURPOSE: To conduct a scoping review to
      explore the role of hearing aids in tinnitus management. RESEARCH DESIGN: Scoping
      review based on the six-stage framework of Arksey and O'Malley (2005). STUDY
      SAMPLE: Relevant studies were identified using various databases (Scopus, Google
      Scholar, SpringerLink, and PubMed) and hand searching of journals and a reference
      list of articles. Out of 277 shortlisted articles, 29 studies (18 research
      studies and 11 reviews) were chosen for charting of data based on their
      abstracts. DATA COLLECTION AND ANALYSIS: Tinnitus assessment measures used in
      studies were recorded along with changes in their scores. Measures used in
      studies included the Tinnitus Handicap Inventory (THI), Tinnitus Handicap
      Questionnaire (THQ), Tinnitus Severity Index (TSI), Tinnitus Reaction
      Questionnaire (TRQ), German version of Tinnitus Questionnaire (TQ), Beck
      Depression Inventory (BDI), and visual analogue scale (VAS) of tinnitus
      intensity. Where possible Cohen's d effect size statistic was calculated.
      RESULTS: Although the quality of evidence for hearing aids' effect on tinnitus is
      not strong, the weight of evidence (17 research studies for, 1 against) suggests
      merit in using hearing aids for tinnitus management. CONCLUSIONS: The majority of
      studies reviewed support the use of hearing aids for tinnitus management.
      Clinicians should feel reassured that some evidence shows support for the use of
      hearing aids for treating tinnitus, but there is still a need for stronger
      methodology and randomized control trials.

PMID- 24131612
TI  - No Evidence of Genotoxic Damage in a Group of Patients with Titanium Dental
      Implants and Different Metal Restorations in the Oral Cavity.
AB  - BACKGROUND: Titanium is the most widely used metal in implant dentistry. In spite
      of its biocompatibility, when it is released into the oral environment, it can
      have local negative biological effects. PURPOSE: The aims of this study were to
      detect the concentration of metal ions in patients with dental implants, to
      evaluate whether or not their release might be influenced by the presence of
      other metals, and to assay whether these ions might provoke genotoxic damage in
      oral mucosa cells. MATERIALS AND METHODS: One hundred five patients with a total
      of 180 dental implants were included. The sample was divided into seven groups (n
      = 15 per group). Group 1 consisted of patients with metal-porcelain fixed crowns
      on dental implants; Group 2, patients with metal-porcelain fixed crowns on teeth;
      Group 3, patients with dental amalgams; Group 4, patients with metal-porcelain
      fixed crowns on dental implants and metal-porcelain fixed crowns on teeth; Group
      5, patients with metal-porcelain fixed crowns on dental implants and dental
      amalgams; and Group 6, patients with metal-porcelain fixed crowns on dental
      implants, metal-porcelain fixed crowns on teeth, and dental amalgams. Group 7 was
      the control group, without any dental treatment. The concentration of metal ions
      was detected using inductively coupled plasma mass spectrometry; genotoxicity was
      measured using the buccal micronucleus cytome assay protocol. RESULTS: Group 5
      displayed the highest concentration of metal ions in parts per billion (Ti, Co,
      Ni, Zn, Pd, Sn, and Pb). Group 6 was characterized by the highest presence of Hg.
      No signs of genotoxic damage were found in any of the study groups. CONCLUSIONS:
      Patients with titanium dental implants combined with other metal restorations
      presented higher concentrations of metal ions, but no genotoxic damage was
      observed in oral mucosal epithelial cells.

PMID- 24131613
TI  - Counting the costs of cancer care.

PMID- 24131614
TI  - Economic burden of cancer across the European Union: a population-based cost
      analysis.
AB  - BACKGROUND: In 2008, 2.45 million people were diagnosed with cancer and 1.23
      million died because of cancer in the 27 countries of the European Union (EU). We
      aimed to estimate the economic burden of cancer in the EU. METHODS: In a
      population-based cost analysis, we evaluated the cost of all cancers and also
      those associated with breast, colorectal, lung, and prostate cancers. We obtained
      country-specific aggregate data for morbidity, mortality, and health-care
      resource use from international and national sources. We estimated health-care
      costs from expenditure on care in the primary, outpatient, emergency, and
      inpatient settings, and also drugs. Additionally, we estimated the costs of
      unpaid care provided by relatives or friends of patients (ie, informal care),
      lost earnings after premature death, and costs associated with individuals who
      temporarily or permanently left employment because of illness. FINDINGS: Cancer
      cost the EU ?126 billion in 2009, with health care accounting for ?51.0 billion
      (40%). Across the EU, the health-care costs of cancer were equivalent to ?102 per
      citizen, but varied substantially from ?16 per person in Bulgaria to ?184 per
      person in Luxembourg. Productivity losses because of early death cost ?42.6
      billion and lost working days ?9.43 billion. Informal care cost ?23.2 billion.
      Lung cancer had the highest economic cost (?18.8 billion, 15% of overall cancer
      costs), followed by breast cancer (?15.0 billion, 12%), colorectal cancer (?13.1
      billion, 10%), and prostate cancer (?8.43 billion, 7%). INTERPRETATION: Our
      results show wide differences between countries, the reasons for which need
      further investigation. These data contribute to public health and policy
      intelligence, which is required to deliver affordable cancer care systems and
      inform effective public research funds allocation.

PMID- 24131615
TI  - Pollination in a patchily distributed lousewort is facilitated by presence of a
      co-flowering plant due to enhancement of quantity and quality of pollinator
      visits.
AB  - BACKGROUND AND AIMS: Plants surrounded by individuals of other co-flowering
      species may suffer a reproductive cost from interspecific pollen transfer (IPT).
      However, differences in floral architecture may reduce or eliminate IPT. METHODS:
      A study was made of Pedicularis densispica (lousewort) and its common co
      flowering species, Astragalus pastorius, to compare reproductive and pollination
      success of lousewort plants from pure and mixed patches. Floral architecture and
      pollinator behaviour on flowers of the two plants were compared along with the
      composition of stigmatic pollen load of the louseworts. The extent of pollen
      limitation of plants from pure and mixed patches was also explored through
      supplemental pollination with self- and outcross pollen (PLs and PLx). KEY
      RESULTS: Mixed patches attracted many more nectar-searching individuals of Bombus
      richardsi. These bumble-bees moved frequently between flowers of the two species.
      However, they pollinated P. densispica with their dorsum and A. pastorius with
      their abdomen. This difference in handling almost completely eliminated IPT.
      Lousewort plants from mixed patches yielded more seeds, and seeds of higher mass
      and germinability, than those from pure patches. Moreover, louseworts from mixed
      patches had lower PLs and PLx compared with those from pure patches. CONCLUSIONS:
      Differences in floral architecture induced differences in pollinator behaviour
      that minimized IPT, such that co-flowering plants significantly enhanced quantity
      and quality of pollinator visits for the lousewort plants in patchy habitat.
      These findings add to our understanding of the mechanisms of pollination
      facilitation.

PMID- 24131616
TI  - Ultrasonography for detecting a hog bristle in a finger: a case report and
      literature review.

PMID- 24131617
TI  - Lung cancer mortality and exposure to polycyclic aromatic hydrocarbons in British
      coke oven workers.
AB  - BACKGROUND: Workers on coke oven plants may be exposed to potentially
      carcinogenic polycyclic aromatic hydrocarbons (PAHs), particularly during work on
      the ovens tops. Two cohorts, employees of National Smokeless Fuels (NSF) and the
      British Steel Corporation (BSC) totalling more than 6,600 British coke plant
      workers employed in 1967, had been followed up to mid-1987 for mortality.
      Previous analyses suggested an excess in lung cancer risk of around 25%, or less
      when compared with Social Class IV ('partly skilled').Analyses based on internal
      comparisons within the cohorts identified statistical associations with estimates
      of individual exposures, up to the start of follow-up, to benzene-soluble
      materials (BSM), widely used as a metric for mixtures of PAHs. Some associations
      were also found with times spent in certain coke ovens jobs with specific
      exposure scenarios, but results were not consistent across the two cohorts and
      limitations in the exposure estimates were noted. The present study was designed
      to reanalyse the existing data on lung cancer mortality, incorporating revised
      and improved exposure estimates to BSM and to benzo[a]pyrene (B[a]P), including
      increments during the follow-up and a lag for latency. METHODS: Mean annual
      average concentrations of both BSM and B[a]P were estimated by analysis of
      variance (ANOVA) from concentration measurements at all NSF and six BSC plants,
      and summarised by job and plant, with a temporal trend (for the BSM only). These
      were combined with subjects' work histories, to produce exposure estimates in
      each year of follow-up, with a 10-year lag to allow for latency. Exposures to BSM
      and to B[a]P were sufficiently uncorrelated to permit analysis in relation to
      each variable separately.Lung cancer death risks during the follow-up were
      analysed in relation to the estimated time-dependent exposures, both continuous
      and grouped, using Cox regression models, with adjustment for age. RESULTS:
      Changing the exposure estimates changed the estimated relative risks compared
      with earlier results, but the new analyses showed no significant trends with
      continuous measures of exposure to either BSM or B[a]P, nor with time spent on
      ovens tops. Analyses with grouped exposures showed mixed results. Across all BSC
      plants, the relative risk coefficient for working 5 or more years on ovens tops,
      where the exposures were highest, was 1.81, which was statistically significant.
      However, results for those with 0-5 years on ovens tops did not suggest a trend;
      the evidence for an underlying relationship was thus suggestive but not strong.
      CONCLUSIONS: The new results are in line with previous findings; they show some
      signs consistent with an effect of coke ovens work on lung cancer risk,
      especially on ovens tops, but the preponderant absence of significant results,
      and the inconsistencies between results for NSF and BSC, highlight how little
      evidence there is in these data of any effect.

PMID- 24131618
TI  - Clinician's road map to wavelet EEG as an Alzheimer's disease biomarker.
AB  - Alzheimer's disease (AD) is considered the main cause of dementia in Western
      countries. Consequently, there is a need for an accurate, universal, specific and
      cost-effective biomarker for early AD diagnosis, to follow disease progression
      and therapy response. This article describes a new diagnostic approach to
      quantitative electroencephalogram (QEEG) diagnosis of mild and moderate AD. The
      data set used in this study was composed of EEG signals recorded from 2 groups:
      (S1) 74 normal subjects, 33 females and 41 males (mean age 67 years, standard
      deviation = 8) and (S2) 88 probable AD patients (NINCDS-ADRDA criteria), 55
      females and 33 males (mean age 74.7 years, standard deviation = 7.8) with mild to
      moderate symptoms (DSM-IV-TR). Attention is given to sample size and the use of
      state of the art open source tools (LetsWave and WEKA) to process the EEG data.
      This innovative technique consists in associating Morlet wavelet filter with a
      support vector machine technique. A total of 111 EEG features (attributes) were
      obtained for 162 probands. The results were accuracy of 92.72% and area under the
      curve of 0.92 (percentage split test). Most important, comparing a single patient
      versus the total data set resulted in accuracy of 84.56% (leave-one-patient-out
      test). Particular emphasis was on clinical diagnosis and feasibility of
      implementation of this low-cost procedure, because programming knowledge is not
      required. Consequently, this new method can be useful to support AD diagnosis in
      resource-limited settings. 

PMID- 24131619
TI  - Change in the characteristics of EEG color noise in Alzheimer's disease.
AB  - Neurophysiological experiments support the hypothesis of the presence of critical
      dynamics of brain activity. This is also manifested by power law of
      electroencephalography (EEG) power spectra, which can be described by the
      relation 1/f(alpha). This dependence is a result of internal interactions between
      parts of the brain and is probably required for optimal processing of
      information. In Alzheimer's disease, changes in the functional organization of
      the brain occur, which may be manifested by changes in the alpha coefficient. We
      compared the average values of alpha for 19 electrodes in the resting EEG record
      in 110 patients with moderate to severe Alzheimer's disease (Mini-Mental State
      Examination [MMSE] score = 10-19) with 110 healthy controls. Statistically, the
      most significant differences are present in the prefrontal areas. In addition to
      the prefrontal and frontal areas, the largest separation value in the evaluation
      of receiver operating characteristic (ROC) curves was recorded in the temporal
      area. The coefficient alpha has few false-positive results in the optimal
      operating point of the ROC curve, and is thereby highly specific for Alzheimer's
      disease.

PMID- 24131620
TI  - EEG Differences Between the Combined and Inattentive Types of Attention
      Deficit/Hyperactivity Disorder in Girls: A Further Investigation.
AB  - This study further investigated electroencephalogram (EEG) differences between
      girls with the Combined and Inattentive types of attention-deficit/hyperactivity
      disorder (AD/HD). We selected subjects with widely separated scores on
      hyperactivity-impulsivity symptoms to behaviorally exaggerate diagnostic group
      differences. Twenty girls with AD/HD Combined type, 20 girls with AD/HD
      Inattentive type, and 20 controls (aged 7-12 years) had an eyes-closed resting
      EEG recorded from 19 electrodes. The EEG was fast Fourier transformed, and
      estimates for total power, absolute and relative power in the delta, theta,
      alpha, and beta frequency bands, and the theta/beta ratio were calculated and
      analyzed in 9 scalp regions. Girls of the Combined type, compared with girls of
      the Inattentive type, had elevated midline total power, elevated temporal
      absolute alpha activity, elevated posterior absolute beta activity, reduced right
      hemisphere relative delta and reduced left hemisphere relative alpha activity,
      and reduced theta/beta ratio in the left hemisphere. Although topographic
      differences were again found between the AD/HD types, significant global
      differences remain elusive in the EEGs of girls with the Combined and Inattentive
      types. Despite creating behaviorally exaggerated AD/HD type groups, girls' EEG
      activity failed to replicate differences found previously in mixed-sex groups.
      The EEG profiles of AD/HD types in girls are markedly different from those found
      in boys. This reinforces the notion that it is no longer appropriate to apply the
      male-based literature to all AD/HD groups; rather, the use of single-sex subject
      groups is necessary in EEG research of AD/HD.

PMID- 24131621
TI  - Are chaotic models of EEG signals useful in diagnosing attention
      deficit/hyperactivity disorder?

PMID- 24131622
TI  - The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with
      a poor prognosis and endocrine resistance in breast cancer: a retrospective study
      including patients from the randomised Stockholm tamoxifen trials.
AB  - INTRODUCTION: mTOR and its downstream effectors the 4E-binding protein 1 (4EBP1)
      and the p70 ribosomal S6 kinases (S6K1 and S6K2) are frequently upregulated in
      breast cancer, and assumed to be driving forces in tumourigenesis, in close
      connection with oestrogen receptor (ER) networks. Here, we investigated these
      factors as clinical markers in five different cohorts of breast cancer patients.
      METHODS: The prognostic significance of 4EBP1, S6K1 and S6K2 mRNA expression was
      assessed with real-time PCR in 93 tumours from the treatment randomised Stockholm
      trials, encompassing postmenopausal patients enrolled between 1976 and 1990.
      Three publicly available breast cancer cohorts were used to confirm the results.
      Furthermore, the predictive values of 4EBP1 and p4EBP1_S65 protein expression for
      both prognosis and endocrine treatment benefit were assessed by
      immunohistochemical analysis of 912 node-negative breast cancers from the
      Stockholm trials. RESULTS: S6K2 and 4EBP1 mRNA expression levels showed
      significant correlation and were associated with a poor outcome in all cohorts
      investigated. 4EBP1 protein was confirmed as an independent prognostic factor,
      especially in progesterone receptor (PgR)-expressing cancers. 4EBP1 protein
      expression was also associated with a poor response to endocrine treatment in the
      ER/PgR positive group. Cross-talk to genomic as well as non-genomic ER/PgR
      signalling may be involved and the results further support a combination of ER
      and mTOR signalling targeted therapies. CONCLUSION: This study suggests S6K2 and
      4EBP1 as important factors for breast tumourigenesis, interplaying with hormone
      receptor signalling. We propose S6K2 and 4EBP1 as new potential clinical markers
      for prognosis and endocrine therapy response in breast cancer.

PMID- 24131624
TI  - Making the most out of life: Exploring the contribution of attention restorative
      theory in developing a non-pharmacological intervention for fatigue.
AB  - OBJECTIVES: This study investigates an approach based on Kaplan's Attention
      Restorative Theory (ART) to develop a non-pharmacological intervention to help
      individuals manage the distressing effects of illness related fatigue. The study
      aims to: identify activities perceived as being enjoyable by individuals who have
      moderate to severe fatigue related to advanced illness; determine the core
      attributes of potentially beneficially interventions; analyse reported
      'enjoyable' experiences within the ART framework by mapping emergent themes to
      attributes of attention restoration; and develop the prototype for a self
      management intervention tool. METHODS: A purposive sample of 25 individuals who
      experienced moderate to severe fatigue was selected from the local hospice and
      community. Focused semi-structured interviews probed the questions: What do you
      enjoying doing? What is it about the activity that you particularly enjoy?
      Framework analysis was used to manage responses. RESULTS: Seventy-five 'enjoyable
      experiences' were identified, including artistic pursuits, voluntary work,
      socialising and learning. These activities were organised into four conceptual
      themes: Belonging, Expansive, Nurturing and Purposeful. When mapped against
      attributes of restorative activities specified in ART, there was some congruence
      and variation. It was clear that the participants expressed a great need to be
      safe and in a nurturing environment. Some participants placed a high value in and
      received great joy from contributing to the community; this was not noted in
      previous ART literature. SIGNIFICANCE OF RESULTS: This study has extended
      Kaplan's insightful work on restorative behaviours by revealing the value that
      purposeful, engaging and safe activities hold for people who live with fatigue.
      ART has inspired the research team to develop a self-management intervention tool
      to guide health care practitioners in promoting a non-pharmacological approach to
      manage fatigue through exploring, discovering and promoting experiences which
      engage, excite, nurture and challenge the person. Further research is needed to
      integrate this approach into clinical practice.

PMID- 24131623
TI  - N-benzyladriamycin-14-valerate (AD 198) exhibits potent anti-tumor activity on
      TRAF3-deficient mouse B lymphoma and human multiple myeloma.
AB  - BACKGROUND: TRAF3, a new tumor suppressor identified in human non-Hodgkin
      lymphoma (NHL) and multiple myeloma (MM), induces PKCdelta nuclear translocation
      in B cells. The present study aimed to evaluate the therapeutic potential of two
      PKCdelta activators, N-Benzyladriamycin-14-valerate (AD 198) and ingenol-3
      angelate (PEP005), on NHL and MM. METHODS: In vitro anti-tumor activities of AD
      198 and PEP005 were determined using TRAF3-/- mouse B lymphoma and human patient
      derived MM cell lines as model systems. In vivo therapeutic effects of AD 198
      were assessed using NOD SCID mice transplanted with TRAF3-/- mouse B lymphoma
      cells. Biochemical studies were performed to investigate signaling mechanisms
      induced by AD 198 or PEP005, including subcellular translocation of PKCdelta.
      RESULTS: We found that AD 198 exhibited potent in vitro and in vivo anti-tumor
      activity on TRAF3-/- tumor B cells, while PEP005 displayed contradictory anti- or
      pro-tumor activities on different cell lines. Detailed mechanistic investigation
      revealed that AD 198 did not affect PKCdelta nuclear translocation, but
      strikingly suppressed c-Myc expression and inhibited the phosphorylation of ERK,
      p38 and JNK in TRAF3-/- tumor B cells. In contrast, PEP005 activated multiple
      signaling pathways in these cells, including PKCdelta, PKCalpha, PKCepsilon, NF
      kappaB1, ERK, JNK, and Akt. Additionally, AD198 also potently inhibited the
      proliferation/survival and suppressed c-Myc expression in TRAF3-sufficient mouse
      and human B lymphoma cell lines. Furthermore, we found that reconstitution of c
      Myc expression conferred partial resistance to the anti-proliferative/apoptosis
      inducing effects of AD198 in human MM cells. CONCLUSIONS: AD 198 and PEP005 have
      differential effects on malignant B cells through distinct biochemical
      mechanisms. Our findings uncovered a novel, PKCdelta-independent mechanism of the
      anti-tumor effects of AD 198, and suggest that AD 198 has therapeutic potential
      for the treatment of NHL and MM involving TRAF3 inactivation or c-Myc up
      regulation.

PMID- 24131625
TI  - Clinical comparison of the TonoVet((r)) rebound tonometer and the Tono-Pen
      Vet((r)) applanation tonometer in dogs and cats with ocular disease: glaucoma or
      corneal pathology.
AB  - OBJECTIVE: To compare the TonoVet((r)) rebound tonometer with the Tono-Pen
      Vet((r)) applanation tonometer in a larger number of glaucomatous eyes and to
      evaluate the effect of different corneal pathologies on both tonometers.
      PROCEDURE: In 26 eyes with clinical signs of glaucoma, intraocular pressure (IOP)
      was measured using the TonoVet((r)) followed by the Tono-Pen Vet((r)) . In 29
      eyes with focal corneal pathology (e.g., corneal scarring, edema, pigmentation),
      both tonometers were used successively to measure IOP in one unaffected area of
      the cornea, as well as on the lesion itself. Impact on measurement results was
      assessed comparing the deviation in IOP readings of each tonometer between the
      two localizations. Statistical data analysis included paired t-tests and
      regression analysis using sas software (version 9.2; SAS Institute, Cary, NC).
      RESULTS: In glaucomatous eyes, the TonoVet((r)) consistently yielded higher
      values of IOP than the Tono-Pen Vet((r)) as can be quantified by the regression
      equation IOP (TonoVet((r)) ) [mmHg] = 1.12 * IOP (Tono-Pen Vet((r)) ) [mmHg] +
      11.5 with R(2) = 0.91 and P < 0.0001. Depending on the type and degree of corneal
      pathology, the deviation in IOP resulting from measurements on altered cornea
      ranged from -6 to 16 mmHg for the TonoVet((r)) and -7 to 20 mmHg for the Tono-Pen
      Vet((r)) , respectively. On average, the effect of corneal disease on IOP
      measurements was lower for the TonoVet((r)) by 1.14 mmHg. CONCLUSIONS: Rebound
      tonometry appears to be a valuable alternative to established applanation
      tonometry in patients with ocular disease such as glaucoma and corneal disorders.
      In patients suffering from glaucoma, the same type of tonometer should be used
      for follow-up examinations, as measurement results of the TonoVet((r)) and the
      Tono-Pen Vet((r)) differ substantially with increasing IOP. Corneal pathology has
      considerable influence on both tonometers with the degree of over- or
      underestimation of IOP depending on the alteration of biomechanical properties of
      the cornea inflicted by various corneal pathologies.

PMID- 24131626
TI  - 'Diversion' of methadone or buprenorphine: 'harm' versus 'helping'.
AB  - BACKGROUND: 'Non-compliant' individuals in opioid maintenance treatment, OMT, are
      often met with tight control regimes to reduce the risk of 'diversion', which may
      lead to harm or death among persons outside of OMT. This article explores
      reported practices of, and motivations for, diversion of methadone and
      buprenorphine, in a group of imprisoned individuals in OMT. FINDINGS: 28 in
      depths interviews were conducted among 12 OMT-enrolled, imprisoned individuals,
      most of whom were remand prisoners. All had experienced tight control regimes
      prior to imprisonment due to varying degrees of 'non-compliance' and illicit drug
      use during treatment. Their acquired norm of sharing with others in a drug using
      community was maintained when entering OMT. Giving one's prescription opioids to
      an individual in withdrawal was indeed seen as an act of helping, something that
      takes on particular significance for couples in which only one partner is
      included in OMT and the other is using illicit heroin. Individuals enrolled in
      OMT might thus be trapped between practicing norms of helping and sharing and
      adhering to treatment regulations. 'Diversion', as this term is conventionally
      used, is not typically understood as practices of giving and helping, but may
      nevertheless be perceived as such by those who undertake them. CONCLUSIONS: As we
      see it, the need to sustain oneself as a decent person in one's own eyes and
      those of others through practices such as sharing and helping should be
      recognized. Treatment providers should consider including couples in which both
      individuals are motivated for starting OMT.

PMID- 24131627
TI  - The horror of unsafe abortion: case report of a life threatening complication in
      a 29-year old woman.
AB  - BACKGROUND: Every year 42 million women with unintended pregnancies choose
      abortion, and fifty percent of these procedures, 20 million are unsafe. An unsafe
      abortion is defined as a procedure for terminating an unintended pregnancy
      carried out either by person lacking the necessary skills or in an environment
      that does not conform to minimal medical standards or both.Pakistan is the one of
      the six countries where more than 50% of the world's all maternal deaths occur.
      It is estimated that 890,000 induced abortions are performed annually in
      Pakistan, and estimate an annual abortion rate of 29 per 1000 women aged 15-49.
      CASE PRESENTATION: Here we present a case report of a 29-year old woman who
      underwent an unsafe abortion for unintended pregnancy resulting in uterine
      perforation. The unskilled provider pulled out her bowel through vagina after
      perforating the uterus, as a result she lost major portion of her small intestine
      resulting in short bowel syndrome. CONCLUSION: The law of Pakistan only allows
      abortion during early stages of pregnancy for purpose of saving the life of a
      mother but does not cater for cases of rape, incest and fetal abnormalities or
      social reasons.Only legalization of abortion is not sufficient, preventing
      unintended pregnancy should be the priority of all the nations and for this
      reason contraception should be widely accessible.Practitioners need to become
      better trained in safer abortion methods and be to able transfer the patient to
      health facility when complications occur.

PMID- 24131628
TI  - Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and
      stromal adrenocortical cell lineages in M. musculus.
AB  - The lineage relationships of fetal adrenal cells and adrenal capsular cells to
      the differentiated adrenal cortex are not fully understood. Existing data support
      a role for each cell type as a progenitor for cells of the adult cortex. This
      report reveals that subsets of capsular cells are descendants of fetal
      adrenocortical cells that once expressed Nr5a1. These fetal adrenocortical cell
      descendants within the adrenal capsule express Gli1, a known marker of
      progenitors of steroidogenic adrenal cells. The capsule is also populated by
      cells that express Tcf21, a known inhibitor of Nr5a1 gene expression. We
      demonstrate that Tcf21-expressing cells give rise to Nr5a1-expressing cells but
      only before capsular formation. After the capsule has formed, capsular Tcf21
      expressing cells give rise only to non-steroidogenic stromal adrenocortical
      cells, which also express collagen 1a1, desmin and platelet-derived growth factor
      (alpha polypeptide) but not Nr5a1. These observations integrate prior
      observations that define two separate origins of adult adrenocortical
      steroidogenic cells (fetal adrenal cortex and/or the adrenal capsule). Thus,
      these observations predict a unique temporal and/or spatial role of adult
      cortical cells that arise directly from either fetal cortical cells or from fetal
      cortex-derived capsular cells. Last, the data uncover the mechanism by which two
      populations of fetal cells (fetal cortex derived Gli1-expressing cells and
      mesenchymal Tcf21-expressing mesenchymal cells) participate in the establishment
      of the homeostatic capsular progenitor cell niche of the adult cortex. 

PMID- 24131629
TI  - Regulation of maternal Wnt mRNA translation in C. elegans embryos.
AB  - The restricted spatiotemporal translation of maternal mRNAs, which is crucial for
      correct cell fate specification in early C. elegans embryos, is regulated
      primarily through the 3'UTR. Although genetic screens have identified many
      maternally expressed cell fate-controlling RNA-binding proteins (RBPs), their in
      vivo targets and the mechanism(s) by which they regulate these targets are less
      clear. These RBPs are translated in oocytes and localize to one or a few
      blastomeres in a spatially and temporally dynamic fashion unique for each protein
      and each blastomere. Here, we characterize the translational regulation of
      maternally supplied mom-2 mRNA, which encodes a Wnt ligand essential for two
      separate cell-cell interactions in early embryos. A GFP reporter that includes
      only the mom-2 3'UTR is translationally repressed properly in oocytes and early
      embryos, and then correctly translated only in the known Wnt signaling cells. We
      show that the spatiotemporal translation pattern of this reporter is regulated
      combinatorially by a set of nine maternally supplied RBPs. These nine proteins
      all directly bind the mom-2 3'UTR in vitro and function as positive or negative
      regulators of mom-2 translation in vivo. The net translational readout for the
      mom-2 3'UTR reporter is determined by competitive binding between positive- and
      negative-acting RBPs for the 3'UTR, along with the distinct spatiotemporal
      localization patterns of these regulators. We propose that the 3'UTR of maternal
      mRNAs contains a combinatorial code that determines the topography of associated
      RBPs, integrating positive and negative translational inputs. 

PMID- 24131630
TI  - A Pitx transcription factor controls the establishment and maintenance of the
      serotonergic lineage in planarians.
AB  - In contrast to adult vertebrates, which have limited capacities for neurogenesis,
      adult planarians undergo constitutive cellular turnover during homeostasis and
      are even able to regenerate a whole brain after decapitation. This enormous
      plasticity derives from pluripotent stem cells residing in the planarian body in
      large numbers. It is still obscure how these stem cells are programmed for
      differentiation into specific cell lineages and how lineage identity is
      maintained. Here we identify a Pitx transcription factor of crucial importance
      for planarian regeneration. In addition to patterning defects that are co
      dependent on the LIM homeobox transcription factor gene islet1, which is
      expressed with pitx at anterior and posterior regeneration poles, RNAi against
      pitx results in islet1-independent specific loss of serotonergic (SN) neurons
      during regeneration. Besides its expression in terminally differentiated SN
      neurons we found pitx in stem cell progeny committed to the SN fate. Also, intact
      pitx RNAi animals gradually lose SN markers, a phenotype that depends neither on
      increased apoptosis nor on stem cell-based turnover or transdifferentiation into
      other neurons. We propose that pitx is a terminal selector gene for SN neurons in
      planarians that controls not only their maturation but also their identity by
      regulating the expression of the Serotonin production and transport machinery.
      Finally, we made use of this function of pitx and compared the transcriptomes of
      regenerating planarians with and without functional SN neurons, identifying at
      least three new neuronal targets of Pitx. 

PMID- 24131631
TI  - A dynamic population of stromal cells contributes to the follicle stem cell niche
      in the Drosophila ovary.
AB  - Epithelial stem cells are maintained within niches that promote self-renewal by
      providing signals that specify the stem cell fate. In the Drosophila ovary,
      epithelial follicle stem cells (FSCs) reside in niches at the anterior tip of the
      tissue and support continuous growth of the ovarian follicle epithelium. Here, we
      demonstrate that a neighboring dynamic population of stromal cells, called escort
      cells, are FSC niche cells. We show that escort cells produce both Wingless and
      Hedgehog ligands for the FSC lineage, and that Wingless signaling is specific for
      the FSC niche whereas Hedgehog signaling is active in both FSCs and daughter
      cells. In addition, we show that multiple escort cells simultaneously encapsulate
      germ cell cysts and contact FSCs. Thus, FSCs are maintained in a dynamic niche by
      a non-dedicated population of niche cells. 

PMID- 24131632
TI  - Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption
      of the myotendinous junction.
AB  - The myotendinous junction (MTJ) is the major site of force transfer in skeletal
      muscle, and defects in its structure correlate with a subset of muscular
      dystrophies. Col22a1 encodes the MTJ component collagen XXII, the function of
      which remains unknown. Here, we have cloned and characterized the zebrafish
      col22a1 gene and conducted morpholino-based loss-of-function studies in
      developing embryos. We showed that col22a1 transcripts localize at muscle ends
      when the MTJ forms and that COLXXII protein integrates the junctional
      extracellular matrix. Knockdown of COLXXII expression resulted in muscular
      dystrophy-like phenotype, including swimming impairment, curvature of embryo
      trunk/tail, strong reduction of twitch-contraction amplitude and contraction
      induced muscle fiber detachment, and provoked significant activation of the
      survival factor Akt. Electron microscopy and immunofluorescence studies revealed
      that absence of COLXXII caused a strong reduction of MTJ folds and defects in
      myoseptal structure. These defects resulted in reduced contractile force and
      susceptibility of junctional extracellular matrix to rupture when subjected to
      repeated mechanical stress. Co-injection of sub-phenotypic doses of morpholinos
      against col22a1 and genes of the major muscle linkage systems showed a
      synergistic gene interaction between col22a1 and itga7 (alpha7beta1 integrin)
      that was not observed with dag1 (dystroglycan). Finally, pertinent to a conserved
      role in humans, the dystrophic phenotype was rescued by microinjection of
      recombinant human COLXXII. Our findings indicate that COLXXII contributes to the
      stabilization of myotendinous junctions and strengthens skeletal muscle
      attachments during contractile activity. 

PMID- 24131633
TI  - Emilin3 is required for notochord sheath integrity and interacts with Scube2 to
      regulate notochord-derived Hedgehog signals.
AB  - The notochord is a transient and essential structure that provides both
      mechanical and signaling cues to the developing vertebrate embryo. In teleosts,
      the notochord is composed of a core of large vacuolated cells and an outer layer
      of cells that secrete the notochord sheath. In this work, we have identified the
      extracellular matrix glycoprotein Emilin3 as a novel essential component of the
      zebrafish notochord sheath. The development of the notochord sheath is impaired
      in Emilin3 knockdown embryos. The patterning activity of the notochord is also
      affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in
      Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing
      Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3
      modulates the availability of Hh ligands by interacting with the permissive
      factor Scube2 in the notochord sheath. Overall, this study reveals a new role for
      an EMILIN protein and reinforces the concept that structure and function of the
      notochord are strictly linked. 

PMID- 24131634
TI  - Location of transient ectodermal progenitor potential in mouse development.
AB  - Ectoderm is one of the three classic germ layers in the early mouse embryo, with
      the capacity to develop into both the central nervous system and epidermis.
      Because it is a transient phase of development with few molecular markers, the
      early ectoderm is the least understood germ layer in mouse embryonic development.
      In this work, we studied the differentiation potential of isolated ectoderm
      tissue in response to BMP signaling at various developmental stages (E6.5, E7.0
      and E7.5), and identified a transient region in the anterior-proximal side of the
      embryo at E7.0 that possesses the ability to become neural or epidermal ectoderm
      in response to the absence or presence of BMP4, respectively. Furthermore, we
      demonstrated that inhibition of Nodal signaling could direct the pluripotent E6.5
      epiblast cells towards ectoderm lineages during differentiation in explants in
      vitro. Our work not only improves our understanding of ectodermal layer
      development in early embryos, but also provides a framework for regenerative
      differentiation towards ectodermal tissues. 

PMID- 24131635
TI  - Cardiac manifestations other than valvulopathy in antiphospholipid syndrome: long
      time echocardiography follow-up study.
AB  - AIM: Non-valvular cardiac disease in the antiphospholipid syndrome (APS) has been
      scanty studied. We wanted to assess the prevalence and evolution of left
      myocardial disease, pulmonary hypertension and intracardiac thrombi in a cohort
      of APS patients. METHOD: A total of 53 patients with APS, either primary (n = 34,
      64%) or associated to lupus (n = 19, 36%) and 20 controls were included. Initial
      transthoracic echocardiography assessment was performed in patients at diagnosis,
      with echocardiography controls performed along mean follow-up of 12 years.
      Prevalence of myocardial disease in APS cohort was assessed taking into account
      primary risk factors (hemodynamically significant valvular disease, systemic
      hypertension, diabetes, alcoholism, myocardial infarction or myocarditis), the
      same as for pulmonary hypertension (severe left ventricular dysfunction or
      chronic lung disease). RESULTS: Left myocardial disease had a prevalence of 3.8%
      (2/53 patients), not different from controls (P = 0.12). Both patients had
      diastolic dysfunction grade I that maintained stability throughout
      echocardiographic follow-up period. Pulmonary hypertension had a prevalence of
      11.3% (6/53 patients), not different from controls (P = 0.12); all cases were
      related to pulmonary embolism. Patients diagnosed with pulmonary hypertension in
      baseline maintained stable pressures throughout follow-up in the absence of new
      thrombosis. Intracardiac thrombi had a prevalence of 1.8% (1/53 patients), not
      different from controls (P = 0.4), without changes along echocardiographic follow
      up. CONCLUSION: Pulmonary hypertension is the most prevalent non-valvular cardiac
      manifestation in APS, with an evolution associated with thromboembolic disease,
      while left myocardial disease and intracardiac thrombi would be rare
      manifestations in APS.

PMID- 24131636
TI  - Molecular targets for antifibrotic therapy in liver disease: using magic bullets
      for crossfire rather than a one-sided shotgun attack.

PMID- 24131637
TI  - Reduced fibrosis in recurrent HCV with tacrolimus, azathioprine and steroids
      versus tacrolimus: randomised trial long term outcomes.
AB  - OBJECTIVE: Early results of a randomised trial showed reduced fibrosis due to
      recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy
      (MT) following transplantation for HCV cirrhosis. We evaluated the clinical
      outcomes after a median 8 years of follow-up, including differences in fibrosis
      assessed by collagen proportionate area (CPA). DESIGN: 103 consecutive liver
      transplant recipients with HCV cirrhosis receiving cadaveric grafts were
      randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.1 mg/kg
      divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing
      off to zero by 6 months. Both groups had serial transjugular biopsies with
      hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4
      was the predetermined endpoint. CPA was measured in all biopsies. Factors
      associated with HCV recurrence were evaluated. Clinical decompensation was the
      first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy.
      RESULTS: No significant preoperative, peri-operative or postoperative differences
      between groups were found. During 96 months median follow-up, stage 4 fibrosis
      was reached in 19 MT/11 TT with slower fibrosis progression in TT (p=0.009). CPA
      at last biopsy was 12% in MT and 8% in TT patients (p=0.004). 14 MT/ three TT
      patients reached HVPG>=10 mm Hg (p=0.002); 10 MT/three TT patients,
      decompensated. Multivariately, allocated MT (p=0.047, OR 3.23, 95% CI 1.01 to
      10.3) was independently associated with decompensation: 14 MT/ seven TT died, and
      five MT/ four TT were retransplanted. CONCLUSIONS: Long term immunosuppression
      with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis
      recipients resulted in slower progression to severe fibrosis assessed by Ishak
      stage and CPA, less portal hypertension and decompensation, compared with
      tacrolimus alone. ISRCTN94834276--Randomised study for immunosuppression regimen
      in liver transplantation.

PMID- 24131638
TI  - Taste receptors of the gut: emerging roles in health and disease.
AB  - Recent progress in unravelling the nutrient-sensing mechanisms in the taste buds
      of the tongue has triggered studies on the existence and role of chemosensory
      cells in the gut. Indeed, the gastrointestinal tract is the key interface between
      food and the human body and can sense basic tastes in much the same way as the
      tongue, through the use of similar G-protein-coupled taste receptors. These
      receptors 'taste' the luminal content and transmit signals that regulate nutrient
      transporter expression and nutrient uptake, and also the release of gut hormones
      and neurotransmitters involved in the regulation of energy and glucose
      homeostasis. Hence, they play a prominent role in the communication between the
      lumen, epithelium, smooth muscle cells, afferent nerve fibres and the brain to
      trigger adaptive responses that affect gastrointestinal function, food intake and
      glucose metabolism. This review summarises how sensing of nutrients by taste
      receptors along the gut plays a key role in the process of digestion, and how
      disturbances or adaptations of these chemosensory signalling pathways may
      contribute to the induction or resolution of a number of pathological conditions
      related to diabetes, obesity, or diet-induced symptom generation in irritable
      bowel syndrome. Targeting these receptors may represent a promising novel route
      for the treatment of a number of these diseases. 

PMID- 24131652
TI  - Strengthening the evidence-policy interface for patient safety: enhancing global
      health through hospital partnerships.
AB  - Strengthening the evidence-policy interface is a well-recognized health system
      challenge in both the developed and developing world. Brokerage inherent in
      hospital-to-hospital partnerships can boost relationships between "evidence" and
      "policy" communities and move developing countries towards evidence based patient
      safety policy. In particular, we use the experience of a global hospital
      partnership programme focused on patient safety in the African Region to explore
      how hospital partnerships can be instrumental in advancing responsive decision
      making, and the translation of patient safety evidence into health policy and
      planning. A co-developed approach to evidence-policy strengthening with seven
      components is described, with reflections from early implementation. This rapidly
      expanding field of enquiry is ripe for shared learning across continents, in
      keeping with the principles and spirit of health systems development in a
      globalized world. 

PMID- 24131653
TI  - (S)-1-(4-Dimethylaminophenylcarbonyl)-3-aminopyrrolidine: a derivatization
      reagent for enantiomeric separation and sensitive detection of chiral carboxylic
      acids by LC/ESI-MS/MS.
AB  - A novel derivatization reagent, (S)-1-(4-dimethylaminophenylcarbonyl)-3
      aminopyrrolidine (1-DAPAP), was developed for increasing the detection
      sensitivity and enantiomeric separation of chiral carboxylic acids by liquid
      chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). 1
      DAPAP reacted with carboxylic acids at room temperature within 5min in the
      presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride.
      The epimerization (racemization) during the derivatization reaction was
      negligible. The resulting derivatives were highly responsive during the ESI-MS
      operating in the positive-ion mode and gave a characteristic product ion during
      the MS/MS, which enabled the sensitive detection using selected reaction
      monitoring; the detection responses of the 1-DAPAP-derivatives were increased by
      10-1100-fold over the intact carboxylic acids and the limits of detection ranged
      from 0.97 and 5.2fmol on the column. The 1-DAPAP-derivatization was also
      effective for the enantiomeric separation of chiral carboxylic acids; the
      resolution values were 1.2-4.3 for the evaluated carboxylic acids. The
      derivatization procedure was successfully applied to biological sample analyses;
      the derivatization followed by LC/ESI-MS/MS enabled the separation and detection
      of trace amounts of ibuprofen and naproxen in human saliva with a simple
      pretreatment and small sample volume. 

PMID- 24131654
TI  - [Glenohumeral instability in patients over 40 years-old: injuries, treatment and
      complications].
AB  - INTRODUCTION: Recurrent shoulder dislocation is infrequent after forty years and
      presents different injuries than younger patients. OBJECTIVE: To compare injuries
      and complications after surgery between one group older than forty years of age
      and another younger group. MATERIAL AND METHODS: A review was made o all patients
      who had undergone arthroscopic surgery due to glenohumeral instability from 1999
      until 2011. The mean follow-up was 64 months. The case group consisted of all
      patients older than 40 years at the time of the surgery (n=21), which was
      compared with a similar sized control group of randomly selected younger patients
      (n=27). RESULTS: The mean age in the older group was 54 years (SD 11.86), while
      it was 26 years (SD 5.80) in the younger group. No differences were founded
      between both groups in labrum injury, Hill-Sachs injury, and bone Bankart lesion
      (P>.05). Rotator cuff tears were 7.3 times (95% CI; 2.5-21.6) more frequent in
      the older group (81%) compared to the younger group (P<.05). However,
      neurological injuries after dislocation were not more frequent in this group.
      There was no significant difference between the complications after surgery and
      the age according to the design (P>.05). CONCLUSIONS: Anterior recurrent
      dislocation after forty years of age is usually associated with rotator cuff
      tears. Arthroscopic treatment of instability was effective with no more
      postoperative complications.

PMID- 24131656
TI  - Lipopolysaccharide infusion enhances dynamic cerebral autoregulation without
      affecting cerebral oxygen vasoreactivity in healthy volunteers.
AB  - INTRODUCTION: Sepsis may be associated with disturbances in cerebral oxygen
      transport and cerebral haemodynamic function, thus rendering the brain
      particularly susceptible to hypoxia. The purpose of this study was to assess the
      impact of isocapnic hypoxia and hyperoxia on dynamic cerebral autoregulation in a
      human-experimental model of the systemic inflammatory response during the early
      stages of sepsis. METHODS: A total of ten healthy volunteers were exposed to
      acute isocapnic inspiratory hyperoxia (FIO2 = 40%) and hypoxia (FIO2 = 12%)
      before and after a 4-hour lipopolysaccharide (LPS) infusion (2 ng kg-1). Middle
      cerebral artery blood follow velocity was assessed using transcranial Doppler
      ultrasound, and dynamic autoregulation was evaluated by transfer function
      analysis. RESULTS: Transfer function analysis revealed an increase in the phase
      difference between mean arterial blood pressure and middle cerebral artery blood
      flow velocity in the low frequency range (0.07-0.20 Hz) after LPS (P<0.01). In
      contrast, there were no effects of either isocapnic hyperoxia or hypoxia on
      dynamic autoregulation, and the cerebral oxygen vasoreactivity to both hyperoxia
      and hypoxia was unaffected by LPS. CONCLUSIONS: The observed increase in phase
      suggests that dynamic cerebral autoregulation is enhanced after LPS infusion and
      resistant to any effects of acute hypoxia; this may protect the brain from
      ischaemia and/or blood-brain barrier damage during the early stages of sepsis.

PMID- 24131657
TI  - Local flap therapy for the treatment of pressure sore wounds.
AB  - The aim of this study was to analyse the effectiveness of an interdisciplinary
      cooperation between conservative and surgical disciplines for the treatment of
      pressure sores (PS). From January 2004 to December 2005, a single-centre study
      was performed with paraplegic and tetraplegic patients presenting with PS grades
      III-V. Outcome measures were defect size, grade, method of reconstruction,
      complication and recurrence rate as well as average length of hospitalisation. A
      total of 119 patients aged 22-84 years with totally 170 PS were included. The
      most common PS were located in the ischial region (47%), followed by the sacral
      (18%), trochanteric (11%), foot (9%) and the malleolar (8%) regions. Defect sizes
      ranged between 4 and 255 cm(2) . Grade IV was the most common PS (68%), followed
      by grade III (30%) and grade V (2%) PS. For wound closure, fasciocutaneous flaps
      were used most frequently (71%), followed by skin grafts (10%) and myocutaneous
      flaps (7%). Postoperative follow-up ranged between 6 and 38 months. The overall
      complication and recurrence rate was 26% and 11%, respectively. If no
      complication occurred, the average duration of hospitalisation stay after the
      first debridement was 98 +/- 62 days. In conclusion, our treatment concept is
      reliable, effective and results in a low recurrence rate. The complication rate,
      even though favourable when compared with the literature, still needs to be
      improved. 

PMID- 24131658
TI  - Clinical significance of L-type amino acid transporter 1 expression as a
      prognostic marker and potential of new targeting therapy in biliary tract cancer.
AB  - BACKGROUND: The expression of L-type amino acid transporter 1 (LAT1) has been
      described to play essential roles in tumor cell growth and survival. However, it
      remains unclear about the clinicopathological significance of LAT1 expression in
      biliary tract cancer. This study was conducted to determine biological
      significance of LAT1 expression and investigate whether LAT1 could be a
      prognostic biomarker for biliary tract cancer. METHODS: A total of 139
      consecutive patients with resected pathologic stage I-IV biliary tract
      adenocarcinoma were retrospectively reviewed. Tumor specimens were stained by
      immunohistochemistry for LAT1, Ki-67, microvessel density determined by CD34, and
      p53; and prognosis of patients was correlated. Biological significance of LAT1
      expression was investigated by in vitro and in vivo experiments with LAT
      inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using
      cholangiocarcinoma cell line. RESULTS: In total patients, high LAT1 expressions
      were recognized in 64.0%. The expression of LAT1 was closely correlated with
      lymphatic metastases, cell proliferation and angiogenesis, and was a significant
      indicator for predicting poor outcome after surgery. LAT1 expression was a
      significant independent predictor by multivariate analysis. Both in vitro and in
      vivo preliminary experiments indicated that BCH significantly suppressed growth
      of the tumor and yielded an additive therapeutic efficacy to gemcitabine and 5
      FU. CONCLUSIONS: High expression of LAT1 is a promising pathological marker to
      predict the outcome in patients with biliary tract adenocarcinoma. Inhibition of
      LAT1 may be an effective targeted therapy for this distressing disease.

PMID- 24131659
TI  - Comprehensive Evaluation of Cryopreserved Bone-Derived Osteoblasts for the Repair
      of Segmental Mandibular Defects in Canines.
AB  - BACKGROUND: The repair of segmental mandibular defects remains challenging in the
      clinic. Previous studies have shown that cryopreserved bone-derived osteoblasts
      (CBOs) have good proliferation and osteogenicity. However, whether these cells
      can be used in the repair of segmental mandibular defects is largely unknown.
      PURPOSE: In this study, we applied CBOs combined with beta-tricalcium phosphate
      (beta-TCP) to repair a segmental mandibular defect in canines and thus
      established the feasibility of using this type of tissue-bank cell for the repair
      of large bone defects in the future. MATERIAL AND METHODS: Sixteen segmental
      mandibular defects in 16 animals were made on the right side. Sequential
      radiographs, computer tomography, polychrome fluorescent labeling,
      immunohistochemical staining, and histological analysis were used to evaluate the
      effects of tissue-engineered bone for segmental mandibular defects. RESULTS: Our
      results demonstrated that CBOs combined with beta-TCP promoted bone
      mineralization and deposition at the early stage, and bony union was achieved in
      the CBO and fresh bone-derived osteoblast (FBO) groups. However, nonunion and
      minimal callus were present in the beta-TCP group. Furthermore, there was a large
      amount of newly formed bone in the CBO and FBO groups and in the autogenous bone
      group. Additionally, osteocalcin immunohistochemistry showed intensive
      osteocalcin immunoreactivity in the bone matrix of the CBO and FBO groups.
      CONCLUSIONS: These data indicate that CBOs implanted in a scaffold can promote
      new bone formation, and this tissue-engineered bone can repair critically sized
      segmental mandibular defects in canines. The use of CBOs combined with beta-TCP
      may be an effective approach for the reconstruction of segmental mandibular
      defects in the clinic.

PMID- 24131661
TI  - A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate
      to-Die Foot-and-Mouth Disease Response Policies II: Waiting Periods After
      Emergency Vaccination in FMD Free Countries.
AB  - For countries with OIE status, FMD free country where vaccination is not
      practised, vaccinate-to-live policies have a significant economic disincentive as
      the trade restriction waiting period is double that of vaccinate-to-die policies.
      The disposal of healthy vaccinated animals strictly for the purpose of regaining
      markets with debatable scientific justification is a global concern. The
      feasibility of aligning the waiting periods to facilitate vaccinate-to-live is
      explored. The first article of this two-part review (Barnett et al., 2015)
      explored the qualities of higher potency Foot-and-Mouth Disease (FMD) vaccines,
      performance of differentiating infected from vaccinated animals (DIVA) diagnostic
      assays particularly in vaccinates and carriers, as well as aspects of current
      limitations of post-outbreak surveillance. Here, the history behind the OIE
      waiting periods for FMD free status is reviewed as well as whether the risk of
      vaccinated animals and their subsequent products differ appreciably at 3 versus 6
      months. It is concluded that alignment is feasible for vaccinate-to-live using
      higher potency FMD vaccines within the current OIE waiting period framework of 3
      and 6 months blocks of time. These waiting periods reflect precedence, historical
      practicalities and considered expert opinion rather than a specific scientific
      rationale. The future lies in updated epidemiological and diagnostic technology
      to establish an acceptable level of statistical certainty for surveillance or
      target probability of freedom of FMDV (infection or circulation) not time
      restricted waiting periods. The OIE Terrestrial Code limits trade from a FMD free
      country where vaccination is not practiced to animal products and live non
      vaccinated animals. The risk of FMDV in products derived from higher potency
      vaccinated animals is appreciably less than for countries with infected FMD
      status or even from a FMD free country where vaccination is practised for which
      the Code has Articles with guidelines for safe trade with time restrictions of 3
      months or less. All these presume that key requirements in the implementation of
      emergency vaccination including appropriate vaccine match, vaccine application,
      susceptible population coverage, etc. are addressed.

PMID- 24131660
TI  - Time perception impairs sensory-motor integration in Parkinson's disease.
AB  - It is well known that perception and estimation of time are fundamental for the
      relationship between humans and their environment. However, this temporal
      information processing is inefficient in patients with Parkinson' disease (PD),
      resulting in temporal judgment deficits. In general, the pathophysiology of PD
      has been described as a dysfunction in the basal ganglia, which is a multisensory
      integration station. Thus, a deficit in the sensorimotor integration process
      could explain many of the Parkinson symptoms, such as changes in time perception.
      This physiological distortion may be better understood if we analyze the
      neurobiological model of interval timing, expressed within the conceptual
      framework of a traditional information-processing model called "Scalar Expectancy
      Theory". Therefore, in this review we discuss the pathophysiology and
      sensorimotor integration process in PD, the theories and neural basic mechanisms
      involved in temporal processing, and the main clinical findings about the impact
      of time perception in PD. 

PMID- 24131662
TI  - Equine deep stromal abscesses (51 cases - 2004-2009)--Part 2: the histopathology
      and immunohistochemical aspect with attention to the histopathologic diagnosis,
      vascular response, and infectious agents.
AB  - PURPOSE: To investigate histopathologic and immunohistochemical aspects of equine
      deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis,
      presumptive etiology, and the immunohistochemical expression of three
      angiogenesis-related factors: vascular endothelial growth factor-A (VEGF-A),
      pigment epithelium-derived factor (PEDF), and interleukin-1 receptor antagonist
      (IL-1ra). SAMPLE POPULATION: Paraffin-embedded biopsy samples from 51 DSA. The
      biopsies were collected from full-thickness penetrating keratoplasty or split
      thickness lamellar keratoplasty surgeries at the University of Florida Veterinary
      Medical Center in the period from 2004 to 2009. PROCEDURE: The histopathologic
      and immunohistochemical findings were tested for association between each other.
      Prevalence calculation and test for association with qualitative data analysis
      was used for data evaluation. RESULTS: Fungal hyphae were found histologically in
      47.1% (n = 24) of the DSA cases. Histopathologically, most fungal DSA showed
      suppurative keratitis (n = 34; 66.7%) and little to no stromal vascularization
      infiltrating the abscess (negative association, P = 0.005). All three
      angiogenesis-related factors were expressed to some degree in DSA tissue. A
      negative association between VEGF-A and PEDF when compared to the presence of
      fungal hyphae (P < 0.001, P = 0.023) indicated that cases positive for these two
      factors will most probably not have fungal hyphae present. CONCLUSION: Abnormally
      decreased VEGF-A expression is suggested as the reason for the slow
      vascularization and delayed resolution of fungal DSA, whereas PEDF and IL-ra did
      not seem to have any influence on the vascularization process. Clinical and
      histopathologic characteristics of DSA make it possible to suggest an etiology
      for an equine DSA with an unknown etiology.

PMID- 24131663
TI  - Cognitive remediation in schizophrenia: background, techniques, evidence of
      efficacy and perspectives.
AB  - Impairment of cognitive functions is a core feature of schizophrenia with
      relevant consequences on patients' psychosocial functioning. Cognitive
      remediation techniques have been recently developed with the aim to restore or
      compensate for such impairments and improve the functional outcome of the
      disease. There is now convincing evidence of the efficacy of many of these
      techniques, especially when delivered in the context of a comprehensive treatment
      programme. Whether the application of these techniques in the early phases of the
      disease could modify the disease course and outcome and how they could affect
      brain plasticity and the trajectory of brain disease of schizophrenia is still
      under scrutiny. 

PMID- 24131664
TI  - Central nervous system penetration of oxycodone after intravenous and epidural
      administration.
AB  - BACKGROUND: Despite being increasingly used for pain management, only two
      studies, with controversial results, have evaluated the epidural use of
      oxycodone. METHODS: Twenty-four women, aged 26-64 yr, undergoing elective
      gynaecological surgery were enrolled in this randomized, double-blinded, parallel
      group study. The subjects were administered either i.v. oxycodone and epidural
      placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12)
      after operation. Oxycodone was administered as a single dose of 0.1 mg kg(-1). An
      epidural catheter for drug administration was placed at T12/L1 and a spinal
      catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were
      frequently collected for the analysis of oxycodone and its major metabolites. The
      primary outcomes were the peak concentration (C(max)), time to peak concentration
      (T(max)), and the exposure (AUC(last)) of oxycodone in CSF and plasma. The
      secondary outcome was the analgesic efficacy, measured as the total dose of
      rescue fentanyl during the first four postoperative hours. RESULTS: In the EPI
      group, the median oxycodone Cmax and AUC(last) in the CSF were 320- and 120-fold
      higher, respectively, compared with the IV group. The total dose of rescue
      fentanyl was significantly lower in the EPI group (seven subjects needed 16
      doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious
      or unexpected adverse events were reported. CONCLUSIONS: Epidural oxycodone
      provides much higher CSF concentrations and possibly better analgesic efficacy
      than does i.v. oxycodone. CLINICAL TRIAL REGISTRATION: EudraCT reference number:
      2011-000125-76.

PMID- 24131665
TI  - Comparison of the effects of xenon and sevoflurane anaesthesia on leucocyte
      function in surgical patients: a randomized trial.
AB  - BACKGROUND: While most anaesthetics are known to suppress immune reactions, data
      from experimental studies indicate the enhancement of reactivity to inflammatory
      stimulators under xenon treatment. We investigated the effect of xenon
      anaesthesia on leucocyte function in surgical patients. METHODS: We performed a
      subgroup analysis of subjects undergoing xenon or sevoflurane anaesthesia in a
      randomized clinical trial. After oral premedication with midazolam, two separate
      blood samples were obtained from subjects undergoing elective abdominal surgery,
      directly before and 1 h after induction of anaesthesia. General anaesthesia was
      maintained with either 60% xenon or 2.0% sevoflurane in 30% O2. Leucocyte count,
      phagocytotic function, and pro-inflammatory cytokine release after ex vivo
      lipopolysaccharide (LPS) stimulation were determined. RESULTS: Except for
      lymphocyte numbers, leucocyte subpopulations did not differ between the groups.
      Phagocytosis and oxidative burst of granulocytes were reduced in both groups
      after 1 h of anaesthesia, whereas monocytes were not affected. Pro-inflammatory
      cytokine release in response to LPS was not affected. CONCLUSIONS: In vivo, xenon
      and sevoflurane anaesthesia did not have a pro-inflammatory effect, at least in
      combination with the types of surgery performed in this study. Notably, the
      impact of xenon anaesthesia did not differ significantly from sevoflurane
      anaesthesia with regard to leucocyte function. However, an underestimation of
      treatment effects due to limited sample sizes cannot be fully excluded.

PMID- 24131666
TI  - Restrictions on antimicrobial use in food animal production: an international
      regulatory and economic survey.
AB  - BACKGROUND: The administration of antimicrobial drugs to food animals at low
      doses for extended durations for growth promotion and disease prevention has been
      linked to the global health crisis of antimicrobial resistance. Internationally,
      multiple jurisdictions have responded by restricting antimicrobial use for these
      purposes, and by requiring a veterinary prescription to use these drugs in food
      animals. Opponents of these policies have argued that restrictions have been
      detrimental to food animal production where they have been adopted. METHODS: We
      surveyed the antimicrobial use policies of 17 political jurisdictions outside of
      the United States with respect to growth promotion, disease prevention, and
      veterinary oversight, and reviewed the available evidence regarding their
      production impacts, including measures of animal health. Jurisdictions were
      included if they were a top-five importer of a major U.S. food animal product in
      2011, as differences between the policies of the U.S. and other jurisdictions may
      lead to trade barriers to U.S. food animal product exports. Jurisdictions were
      also included if information on their policies was publicly available in English.
      We searched the peer-reviewed and grey literatures and corresponded with
      jurisdictions' U.S. embassies, regulators, and local experts. RESULTS:
      Jurisdictions were categorized by whether they prohibit use of antimicrobials for
      growth promotion and/or use of antimicrobials without a veterinary prescription.
      Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of
      use, five jurisdictions have prohibited one use but not the other use, and five
      jurisdictions have not prohibited either use, while information was not available
      for one jurisdiction. Data on the production impacts of these prohibitions were
      limited, although available data, especially from Denmark and Sweden, suggest
      that restrictions on growth promotion use can be implemented with minimal
      production consequences. CONCLUSIONS: A majority of leading U.S. trade partners
      have more stringent policies regarding antibiotic use and veterinary oversight in
      food animal production. Available data suggest that restrictions on growth
      promotion may not be detrimental to production in the long run, although
      additional research could be useful. There is evidence that discordance between
      the U.S. and other jurisdictions with respect to antimicrobial use in food
      animals may be detrimental to U.S. access to export markets for food animal
      products. The available economic evidence strengthens the rationale for
      restricting antimicrobial use in U.S. food animals.

PMID- 24131667
TI  - Evaluating the transport, health and economic impacts of new urban cycling
      infrastructure in Sydney, Australia - protocol paper.
AB  - BACKGROUND: There are repeated calls to build better cycling paths in Australian
      cities if the proportion of people cycling is to increase. Yet the full range of
      transport, health, environmental and economic impacts of new cycling
      infrastructure and the extent to which observed changes are sustained is not well
      understood. The City of Sydney is currently building a new bicycle network, which
      includes a new bicycle path separated from road traffic in the south Sydney area.
      This protocol paper describes a comprehensive method to evaluate this new cycling
      infrastructure. METHOD: A cohort of residents within two kilometres of the new
      bicycle path will be surveyed at baseline before a new section of bicycle path is
      built, and again 12 and 24 months later to assess changes in travel behaviour,
      sense of community, quality of life and health behaviours. Residents in a
      comparable area of Sydney that will not get a new separated bike path will act as
      a comparison group. At baseline a sub-set of residents who volunteer will also
      take a small GPS device with them for one week to assess travel behaviour.
      DISCUSSION: This research should contribute to the advancement in evaluation and
      appraisal methods for cycling projects.

PMID- 24131668
TI  - Contribution of obesity to left atrial and left ventricular dysfunction in
      asymptomatic patients with hypertension: A two-dimensional speckle-tracking
      echocardiographic study.
AB  - Hypertension and obesity each are well known to result in heart failure with
      preserved ejection fraction. Therefore, it is clinically important to clarify the
      mechanisms of further deterioration of left atrial (LA)-left ventricular (LV)
      interaction in asymptomatic patients with obesity in the presence of
      hypertension. Data on conventional and two-dimensional speckle-tracking
      echocardiography (2DSTE) were obtained from 134 asymptomatic hypertensive
      patients. The study sample was divided into two groups: non-obese (n = 80; body
      mass index [BMI] <25 kg/m(2)] and obese (n = 54; BMI >=25 kg/m(2)). The end
      diastolic LV diameter, ratio of early transmitral flow to mitral annular motion
      velocity (E/e'), peak systolic LV circumferential strain rate, and E/e'/peak
      systolic LA strain (S-LAs) were greater in the obese group. Among the
      significantly correlated variables with BMI and E/e'/S-LAs in univariate
      analyses, multivariate analyses revealed that BMI is independently associated
      with end-diastolic LV diameter and peak systolic LV radial strain in all
      hypertensive patients, and that age, systolic blood pressure, relative LV wall
      thickness, peak systolic mitral annular motion velocity (s'), peak systolic LV
      radial strain, and peak early diastolic LV longitudinal strain rate are
      identified as independent predictors related to E/e'/S-LAs in the obese patients,
      whereas only s' contributes to the E/e'/S-LAs in the non-obese patients. Impaired
      LA-LV interaction was accelerated with obesity in the presence of hypertension.
      Assessment of the LA and LV function using 2DSTE provided additional information
      to the negative effects of cardiovascular risk factors on the LA and LV function
      in patients without clinical symptoms.

PMID- 24131669
TI  - Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on
      candesartan-based antihypertensive regimen: results from the study of optimal
      treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial.
AB  - The autoantibodies against angiotensin AT1 receptors (AT1-AAs) in patients with
      essential hypertension exhibited an agonistic action like angiotensin II and
      maintained high blood pressure (BP). Angiotensin II receptor gene (AGTR1)
      polymorphisms were associated with BP response to RAS inhibition in the
      hypertensive population. Furthermore, the BP response to AT1 receptor blockers
      varied significantly among individuals with hypertension. We hypothesized that
      the polymorphisms of the AGTR1 and AT1-AAs might affect antihypertensive response
      to AT1 receptor blockers based in patients with primary hypertension. Patients
      who received a candesartan-based regimen came from the SOT-AT1 study (Study of
      Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor
      Autoantibodies). The established enzyme-labeled immunosorbent assay was used to
      detect AT1-AAs in the sera of the patients. Genotype 3 single nucleotide
      polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among
      AT1-AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect
      candesartan-based were analyzed using SPSS. The percentage of systolic BP
      reduction that was candesartan-based was greater in AT1-AA positive groups than
      in AT1-AA negative ones (21 +/- 8 vs. 18 +/- 9; P = .001). Meanwhile, systolic BP
      reduction that was candesartan-based was more significant in the group of rs5186
      AC genotypes than AA homozygotes after adjusting for other confounding factors
      (37.55 +/- 13.7 vs. 32.47 +/- 17.27 mm Hg; adjusted P = .028). Furthermore,
      haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of
      candesartan therapy. The AT1-AAs, AGTR1 gene polymorphisms and haplotypes solely
      or jointly have influences on candesartan-based antihypertensive response in
      patients with primary hypertension.

PMID- 24131670
TI  - Small employer perspectives on the Affordable Care Act's premiums, SHOP
      exchanges, and self-insurance.
AB  - Beginning January 1, 2014, small businesses having no more than fifty full-time
      equivalent workers will be able to obtain health insurance for their employees
      through Small Business Health Options Program (SHOP) exchanges in every state.
      Although the Affordable Care Act intended the exchanges to make the purchasing of
      insurance more attractive and affordable to small businesses, it is not yet known
      how they will respond to the exchanges. Based on a telephone survey of 604
      randomly selected private firms having 3-50 employees, we found that both firms
      that offered health coverage and those that did not rated most features of SHOP
      exchanges highly but were also very price sensitive. More than 92 percent of
      nonoffering small firms said that if they were to offer coverage, it would be
      "very" or "somewhat" important to them that premium costs be less than they are
      today. Eighty percent of offering firms use brokers who commonly perform
      functions of benefit managers--functions that the SHOP exchanges may assume.
      Twenty-six percent of firms using brokers reported discussing self-insuring with
      their brokers. An increase in the number of self-insured small employers could
      pose a threat to SHOP exchanges and other small-group insurance reforms.

PMID- 24131671
TI  - Relationship between activity of daily living and asteatosis in the lower legs
      among elderly residents in long-term care institutions: a cross-sectional study.
AB  - This cross-sectional observational study investigated the relationship between
      the level of activities of daily living (ADL) and asteatosis in the lower legs
      among elderly residents. We enrolled 173 residents from a long-term care health
      facility and two special nursing homes for elderly persons in the Tokyo
      metropolitan area and Oshima Island, Japan. The level of ADL was measured by the
      Barthel Index. The relationship between the Barthel Index total score and the
      presence of asteatosis in the lower legs diagnosed by a dermatologist was
      analysed by multivariate logistic regression analysis. Among the residents, 79.2%
      had asteatosis in their lower legs. An increase of 1 point in the Barthel Index
      total score was significantly associated with a decreased probability of lower
      leg asteatosis after adjusting for age, sex and the type of institution (adjusted
      odds ratio = 0.982; 95% confidence interval: 0.966-0.998). A higher level of ADL
      is associated with a lower probability of having asteatosis in the lower legs
      among residents in long-term care institutions. Nurses should pay specific
      attention to residents with limited ADL for initiating preventive care for
      asteatosis. 

PMID- 24131673
TI  - Mental health issues decrease diabetes-specific quality of life independent of
      glycaemic control and complications: findings from Australia's living with
      diabetes cohort study.
AB  - BACKGROUND: While factors associated with health-related quality of life for
      people with chronic diseases including diabetes are well researched, far fewer
      studies have investigated measures of disease-specific quality of life. The
      purpose of this study is to assess the impact of complications and comorbidities
      on diabetes-specific quality of life in a large population-based cohort of type 2
      diabetic patients. METHODS: The Living with Diabetes Study recruited participants
      from the National Diabetes Services Scheme in Australia. Data were collected via
      a mailed self-report questionnaire. Diabetes-specific quality of life was
      measured using the Audit of Diabetes-Dependent Quality of Life (ADDQoL)
      questionnaire. The analyses are for 3609 patients with type 2 diabetes.
      Regression models with adjustment for control variables investigated the
      association of complications and comorbidities with diabetes-specific quality of
      life. Next, the most parsimonious model for diabetes-specific quality of life
      after controlling for important covariates was examined. RESULTS: The expected
      associations with better diabetes-specific quality of life were evident, such as
      increased income, not on insulin, better glycaemic control and older age.
      However, being single and having been diagnosed with cancer were also associated
      with better ADDQoL. Additionally, poorer diabetes-specific quality of life was
      strongly sensitive to the presence of diabetes complications and mental health
      conditions such as depression, anxiety and schizophrenia. These relationships
      persisted after adjustment for gender, age, duration of diabetes, treatment
      regimen, sampling region and other treatment and socio-demographic variables.
      CONCLUSIONS: A greater appreciation of the complexities of diabetes-specific
      quality of life can help tailor disease management and self-care messages given
      to patients. Attention to mental health issues may be as important as focusing on
      glycaemic control and complications. Therefore clinicians' ability to identify
      and mange mental health issues and/or refer patients is critical to improving
      patients' diabetes-specific quality of life.

PMID- 24131672
TI  - Deoxyschizandrin, a naturally occurring lignan, is a specific probe substrate of
      human cytochrome P450 3A.
AB  - To accurately predict the modifications done during metabolic processes by
      cytochrome P450 (P450) 3A enzyme, selecting substrates that best represent a
      broad range of substrate substitutions and that follow the Michaelis-Menten
      kinetic properties is highly necessary. In the present study, the oxidative
      pathways of deoxyschizandrin (DS), the most abundant lignan in Fructus
      Schisandrae fruit extract, were characterized with liver microsomes from human
      (HLM) and rat (RLM). Only one monohydroxylated metabolite 7(S)-hydroxylated
      metabolite (isoschizandrin, ISZ), was identified using liquid chromatography-mass
      spectrometry and nuclear magnetic resonance techniques. CYP3A4 and CYP3A5 were
      found to be the major isoforms involved in the monohydroxylation of DS. Also, the
      kinetic studies showed that DS hydroxylation obeyed Michaelis-Menten kinetics
      both in HLM and in RLM. However, the subsequent metabolism of ISZ was nearly
      nonexistent when DS was present. More importantly, the interactions between DS
      and three well characterized CYP3A probe substrates, testosterone (TST),
      midazolam (MDZ), and nifedipine (NIF), were studied. TST and MDZ were shown to
      compete with DS for the mutual binding site, causing Km to be increased. The
      presence of DS also lowered the binding affinities for MDZ and TST. However, DS
      showed only slight inhibitory effects on nifedipine (NIF) oxidation even though
      NIF was able to inhibit DS hydroxylation in a noncompetitive fashion. These
      results show that DS is a good representative substrate of MDZ and TST primarily
      due to their shared, large binding regions on CYP3A. Therefore, DS is an
      attractive candidate as a novel CYP3A probe substrate for predicting the
      metabolic modifications in CYP3A activity. 

PMID- 24131674
TI  - Efficacy and initial dose determination of paricalcitol for treatment of
      secondary hyperparathyroidism in Chinese subjects.
AB  - AIM: Prevalence of secondary hyperparathyroidism (SHPT), a renal disease
      complication, is increasing in China. Available therapies may not optimally
      control SHPT, particularly in patients with hypercalcemia, hyperphosphatemia, and
      parathyroid hyperplasia. This study examined efficacy and safety of two dosing
      regimens of selective vitamin D receptor activator paricalcitol. MATERIALS AND
      METHODS: Subjects with SHPT (n = 216) undergoing hemodialysis were treated with
      paricalcitol i.v. for 12 weeks. One group was treated according to the EU
      paricalcitol package insert (PI) (initial MUg dose based on iPTH/80), and the
      other was treated according to the US PI (initial dose of 0.04 MUg/kg). Dose
      titration was based on iPTH and serum calcium (Ca) and phosphorus (P) levels.
      RESULTS: The primary endpoint of two consecutive >= 30% iPTH decreases was
      achieved by 88.6% and 55.9% of subjects in the EU and US PI groups, respectively.
      Noninferiority of the EU PI group vs. the US PI group was demonstrated (lower
      bound of the 1-sided 97.5% CI = 21.3%). Superiority of the EU PI group was shown
      (lower limit > 0%) and confirmed by Fisher's exact test (p < 0.001); both groups
      showed similar achievement of recommended KDIGO iPTH levels. Ca and P levels were
      relatively constant. CONCLUSION: Both EU and US PI paricalcitol dosing strategies
      effectively reduced iPTH levels in Chinese subjects with SHPT, with minimal
      impact on Ca and P levels.

PMID- 24131675
TI  - Does basiliximab induction trigger lifethreatening ARDS and shock in young
      patients after kidney transplantation?
AB  - BACKGROUND: Kidney disease Improving Global Outcomes (KDIGO) guidelines strongly
      recommend administering an anti-IL-2R mAb (i.e., basiliximab) for induction in
      all kidney transplant recipients. We describe a life-threatening episode of shock
      following basiliximab injection and review the literature. METHODS AND RESULTS: A
      20-year-old male was given tacrolimus, methylprednisolone, mycophenolate, and
      basiliximab, 20 mg in the context of living-related kidney transplantation. On
      post-operative Day 1 (POD 1), he developed acute respiratory distress syndrome
      (ARDS), shock, multiple organ failure, and had a cardiac arrest. After effective
      resuscitation, he received rescue therapies (NO inhalation, extra-corporeal
      membrane oxygenation, and CVVHD) but lost the graft as the result of cortical
      necrosis. We conducted PubMed searches that yielded 7 similar cases; 6 required
      invasive ventilation. Three patients developed cardiac arrest, 3 required major
      inotropic support, and 2 developed MOF and myocardial depression. All but 1
      patient recovered rapidly within a few days. There was no evidence for
      infectious, allergic, or over-hydration concerns. Although the direct causal role
      of basiliximab cannot be formally proven, the fact that ARDS at the time of
      induction therapy with other immunosuppressive agents is otherwise extremely rare
      suggests a direct role for basiliximab. CONCLUSIONS: Basiliximab could be
      associated with shock and ARDS.

PMID- 24131676
TI  - Circulating levels of interleukin-22 in dialysis patients.

PMID- 24131677
TI  - C-reactive protein and carotid and femoral intima media thickness: predicting
      inflammation.
AB  - BACKGROUND: C-reactive protein (CRP) is a recognized marker of systemic
      inflammation. Its association with carotid and femoral intima media thickness
      (surrogate measures of atherosclerosis) may explain excess cardiovascular disease
      risk in hemodialysis patients. OBJECTIVES: To estimate the association between
      CRP and both carotid and femoral IMT in hemodialysis (HD) patients; to predict
      CRP in these patients. METHODS: The present cross-sectional study is nested in
      the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima
      media thickness progression in end-stage renal disease (SUMMER) clinical trial.
      Carotid (common, internal, and bifurcation) and femoral arteries were visualized
      in B-mode ultrasonography. CRP was measured in serum. RESULTS: The study cohort
      included 144 HD patients (39.5% female, mean age 67.8 +/- 11.5 years). All
      measures of both carotid and femoral IMT were significantly positively associated
      with CRP. Subjects with a history of smoking or coronary revascularization had
      significantly higher CRP levels, while subjects treated with sevelamer
      hydrochloride had significantly lower CRP. CRP was significantly positively
      associated with serum phosphorus, calcium, alkaline phosphatase, and PTH, and
      significantly inversely associated with HDL and albumin. CONCLUSIONS: CRP is
      significantly positively associated with both femoral and carotid IMT. Treatment
      with sevelamer hydrochloride is associated with lower CRP in HD patients.

PMID- 24131678
TI  - The clinical spectrum of hemolytic uremic syndrome secondary to complement factor
      H autoantibodies.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with
      significant mortality, progression to end-stage renal disease and recurrence post
      transplantation. The deficiency of CFHR plasma proteins and autoantibody-positive
      hemolytic uremic syndrome (DEAP-HUS) has a more favorable outcome. Guidelines
      suggest plasma therapy be initiated within 24 hours of presentation of aHUS.
      Presentation of aHUS, particularly, DEAP-HUS is associated with a diarrheal
      prodrome in up to 53% of patients and initiation of appropriate therapies is
      frequently delayed. CASES: We report on 3 patients with DEAP-HUS, who presented
      with a diarrheal prodrome that delayed diagnosis and initiation of plasma therapy
      past the 24-hour window recommended. C3 was low in 2 cases at presentation. All
      patients had positive complement factor H (CFH) autoantibodies. Despite delay in
      initiating plasma therapy, all 3 cases remitted with restoration of normal renal
      function following initial presentation. One patient had a relapse but responded
      to further plasma exchange and immunosuppression. The remaining 2 patients were
      relapse-free without maintenance immunosuppression. CONCLUSION: Our cases
      highlight the complexity of diagnosing DEAP-HUS due to the common occurrence of
      diarrhea in the prodromal phase and the subsequent delay in initiating of plasma
      therapy. We therefore advocate a low threshold for testing CFH autoantibodies in
      ambiguous cases where there is no history of bloody diarrhea or Shiga-toxin
      exposure.

PMID- 24131679
TI  - Percutaneous tenotomy for the treatment of diabetic toe ulcers.
AB  - BACKGROUND: Foot ulcers have been implicated as a causative factor in diabetic
      foot amputations. The purpose of this study was to evaluate treating foot ulcers
      in patients with diabetes by percutaneous tenotomy. METHODS: We retrospectively
      reviewed the computerized medical files of 83 patients treated for foot ulcers by
      percutaneous tenotomies. Results were analyzed on the basis of indication and per
      patient. RESULTS: The 83 patients had 160 tenotomies for 4 indications: 103 tip
      of-toe ulcers (treated by flexor digitorum longus tenotomy), 26 cock-up/dorsal
      ulcers (extensor digitorum longus tenotomy), 21 kissing ulcers (extensor
      digitorum longus and/or flexor digitorum longus tenotomies), and 10 plantar
      metatarsal ulcers (extensor digitorum longus with or without flexor digitorum
      longus tenotomy). Healing at 4 weeks was 98%, 96%, 81%, and 0%, respectively. The
      complication rate was very low, with the exception of "transfer lesions," where
      an adjacent toe became involved and needed subsequent tenotomy in 8% of tip-of
      toe ulcers. CONCLUSIONS: Percutaneous tenotomy was an effective and safe method
      for treating toe ulcers in neuropathic patients. It was not effective in treating
      plantar metatarsal ulcers. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24131680
TI  - Periprosthetic osteolysis after total ankle arthroplasty.
AB  - BACKGROUND: Periprosthetic osteolysis in total ankle arthroplasty (TAA) is a
      substantial problem. We report the incidence and characteristics of
      periprosthetic osteolysis and its association with clinical outcomes after TAA
      using the HINTEGRA ankle system. METHODS: Between May 2004 and April 2010, 126
      primary TAA were performed on 115 patients. We excluded 27 ankles with a follow
      up of less than 24 months; thus, 99 ankles in 90 patients with a mean follow-up
      of 40.8 (range, 24-89) months were included in the study. Pain and clinical
      outcomes were assessed using the visual analog scale and the American Orthopaedic
      Foot and Ankle Society score. Fluoroscopy was used for optimum visualization of
      the bone-implant interfaces on radiographs. Computed tomography (CT) was
      conducted on 25 ankles that exhibited progression of osteolysis. RESULTS:
      Radiographs revealed that 37 of the 99 ankles showed radiologic evidence of
      osteolysis; of these, 10 demonstrated continuous progression over the study
      period. Helical CT scans were more accurate than radiographs for identifying and
      measuring periprosthetic osteolysis in TAA. None of the demographic parameters
      were substantially different between the 2 groups of subjects (with or without
      osteolysis). No major association was found between the presence of osteolysis
      and clinical and radiologic outcomes. CONCLUSION: Osteolysis associated with TAA
      may indeed be common in the postoperative period. Although most of the osteolytic
      lesions observed here were relatively quiescent, these lesions raise concerns in
      contemporary TAA because of their incidence rate and the potential for later
      mechanical failure as compared to arthrodesis. Early diagnosis and careful
      evaluation of osteolysis may provide a clinical opportunity for limited revision
      surgery in ankles of impending prosthesis failure. LEVEL OF EVIDENCE: Level IV,
      case series.

PMID- 24131681
TI  - Clinical and microbiological profile of infectious keratitis in children.
AB  - BACKGROUND: Infectious keratitis is a sight-threatening condition for children.
      The purpose of this study was to describe the clinical profile, risk factors and
      microbiological profile of infectious keratitis in children. METHODS:
      Retrospective review of clinical records of patients under 16 years of age with
      history of microbial keratitis seen at a tertiary referral center. Clinical
      characteristics, risk factors, visual and surgical outcomes as well as the
      microbiological profile are analyzed. RESULTS: Forty-one eyes of 41 patients.
      Mean age was 8.7 years. Time between the onset of symptoms and ophthalmological
      examination was 12.7 days. Predisposing factors were found in 78%; ocular trauma
      was the most common (25%). Visual acuity equal or worse than 20/200 at admission
      correlated positively with a poorer visual outcome, p=0.002. Positivity of
      cultures was 34%. Gram-positive bacteria were isolated in 78.5%; Staphylococcus
      epidermidis (28.6%) was the most common microorganism. CONCLUSIONS: Our study
      emphasizes the importance of a prompt diagnosis and treatment of infectious
      corneal ulcers in children. Trauma and contact lenses were the main predisposing
      factors. Gram-positive organisms were isolated in the vast majority of cases and
      visual outcomes are usually poor.

PMID- 24131682
TI  - Lactobacillus plantarum LG42 isolated from gajami sik-hae decreases body and fat
      pad weights in diet-induced obese mice.
AB  - AIMS: This study investigated the antiobesity effect of lactic acid bacteria
      (Lactobacillus plantarum LG42) isolated from gajami sik-hae. METHODS AND RESULTS:
      Male C57BL/6J mice were divided into four groups (n = 10); NDC (normal diet &
      DW), HDC (high-fat diet & DW), LGLAB (high-fat diet & Lactobacillus plantarum
      LG42, 1 * 10(7) CFU per mouse), HGLAB (high-fat diet & L. plantarum LG42, 1 *
      10(9) CFU per mouse). After 12 weeks, GLAB supplemented groups showed lower body
      weight, with a significant reduction in epididymal and back fat. Serum and
      hepatic triglyceride, serum insulin and leptin levels were significantly lowered
      in GLAB supplemented groups. The hepatic mRNA expression of PPARalpha and CPT-I
      were significantly increased in GLAB groups, whereas the level of ACC, SREBP-1
      and LXRalpha were significantly decreased in GLAB groups compared with HDC group.
      Additionally, GLAB reduces the expression of PPARgamma in the epididymal adipose
      tissue resulting in inhibition of genes regulated by PPARgamma. CONCLUSION: These
      results suggest that the Lactobacillus plantarum LG42 has antiobesity effects in
      high-fat-diet-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These
      results may contribute to nutraceutical and food industries in developing
      functional food and probiotics based therapies for the treatment and prevention
      of obesity.

PMID- 24131683
TI  - Prevalence and genotype distribution of Pneumocystis jirovecii in Cuban infants
      and toddlers with whooping cough.
AB  - This study describes the prevalence and genotype distribution of Pneumocystis
      jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban
      infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163
      young Cuban children with WC who were admitted to the respiratory care units at
      two pediatric centers were studied. The prevalence of the organism was determined
      by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large
      subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of
      mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP)
      analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P.
      jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed
      the presence of three different genotypes in the population. Genotype 2 was most
      common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed
      genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR
      products revealed four genotypes, 18% of which were associated with resistance to
      sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95%
      confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke
      (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with
      being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and
      toddlers with WC and the genotyping results provide evidence that this population
      represents a potential reservoir and transmission source of P. jirovecii. 

PMID- 24131684
TI  - Nitrate reductase assay for rapid detection of isoniazid, rifampin, ethambutol,
      and streptomycin resistance in Mycobacterium tuberculosis: a systematic review
      and meta-analysis.
AB  - Colorimetric phenotypic tests recently gained interest because traditional
      primary drug susceptibility testing of Mycobacterium tuberculosis isolates takes
      a long time. We used meta-analysis techniques to review the reliability and
      accuracy of the nitrate reductase assay (NRA), which is one of the most popular
      colorimetric methods to detect resistance to first-line drugs. Medline, PubMed,
      ISI Web, Web of Science, and Google Scholar were used to search for studies
      enrolled in the meta-analysis. The analysis included 35 studies for isoniazid
      (INH), 38 for rifampin (RIF), and 22 for ethambutol (EMB) and streptomycin (STR).
      Summary receiver operating characteristic (SROC) curves were applied to summarize
      diagnostic accuracy. The meta-analyses were performed by the use of Meta-DiSc
      software (version 1.4) and were focused on sensitivity and specificity values for
      measurements of accuracy. The pooled sensitivities were 96% for INH, 97% for RIF,
      90% for EMB, and 82% for STR. The pooled specificities for INH, RIF, EMB, and STR
      were 99%, 100%, 98%, and 96%, respectively. The times required to obtain results
      were between 5 and 28 days by the direct NRA and between 5 and 14 days by the
      indirect test. In conclusion, the present meta-analysis showed that the NRA is a
      reliable low-cost rapid colorimetric susceptibility test that can be used for the
      detection of multidrug-resistant (MDR) tuberculosis, including detection of EMB
      resistance. However, the test appears to have a relatively low sensitivity for
      STR and needs further improvement. 

PMID- 24131685
TI  - Evaluation of the BioFire FilmArray respiratory panel and the GenMark eSensor
      respiratory viral panel on lower respiratory tract specimens.
AB  - We evaluated the performance characteristics of the FilmArray respiratory panel
      and the eSensor respiratory viral panel on clinical and spiked lower respiratory
      tract specimens (LRTS). The overall agreement between the two methods was 89.5%
      (51/57). The lower limit of detection of both assays for all targets in LRTS was
      comparable to that for nasopharyngeal swab specimens. 

PMID- 24131686
TI  - Molecular analysis and clinical significance of Lactobacillus spp. recovered from
      clinical specimens presumptively associated with disease.
AB  - Lactobacillus spp. are part of the normal human flora and are generally assumed
      to be nonpathogenic. We determined the genotypic identification of >100
      Lactobacillus isolates from clinical specimens in the context of presumed
      pathogenic potential (e.g., recovered as the single/predominant isolate from a
      sterile site or at >=10(5) CFU/ml from urine). This study assessed the clinical
      significance and the frequency of occurrence of each Lactobacillus sp. We
      identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of
      which could not be associated with disease. While Lactobacillus rhamnosus,
      Lactobacillus gasseri, and Lactobacillus paracasei were associated with
      infections, L. gasseri was also a common colonizing/contaminating species.
      Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were
      associated with at least one infection. Species commonly used in probiotic
      products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene
      sequencing, to our isolates associated with disease. Human isolates of
      Lactobacillus spp. have differing site associations and levels of clinical
      significance. Knowing the niche and pathogenic potential of each Lactobacillus
      sp. can be of importance to both clinical microbiology and the food and probiotic
      supplement industry. 

PMID- 24131687
TI  - Characteristics of antibody responses in West Nile virus-seropositive blood
      donors.
AB  - West Nile virus (WNV) is now endemic in the United States. Protection against
      infection is thought to be conferred in part by humoral immunity. An
      understanding of the durability and specificity of the humoral response is not
      well established. We studied the magnitude and specificity of antibody responses
      in 370 WNV-seropositive blood donors. We also recalled 18 donors who were
      infected in 2005 to compare their antibody responses at 6 months following
      infection versus at 5 years postinfection. There were no significant differences
      in IgG antibody levels based on age, sex, or recent infection (as evidenced by
      IgM positivity). Specific antibody responses by viral plaque reduction
      neutralization testing (PRNT) were seen in 51/54 subjects evaluated. All donors
      who were seropositive in 2005 remained seropositive at 5 years and maintained
      neutralizing antibodies. IgG levels at 5 years postinfection showed fairly
      minimal decreases compared with the paired levels at 6 months postinfection (mean
      of paired differences,-0.54 signal-to-cutoff ratio (S/CO) units [95% confidence
      interval {CI}, -0.86 to -0.21 S/CO units]) and only minimal decreases in PRNT
      titers. WNV induces a significant antibody response that remains present even 5
      years after infection. 

PMID- 24131688
TI  - Role of pncA and rpsA gene sequencing in detection of pyrazinamide resistance in
      Mycobacterium tuberculosis isolates from southern China.
AB  - We sequenced pncA and rpsA genes plus flanking regions of 161 Mycobacterium
      tuberculosis isolates and found 10 new pncA and 3 novel rpsA mutations in
      pyrazinamide-resistant strains determined by the Bactec MGIT 960 system. The 3'
      end of rpsA might be added as the target of molecular detection of pyrazinamide
      susceptibility. 

PMID- 24131689
TI  - Light microscopy, culture, molecular, and serologic methods for detection of
      herpes simplex virus.
AB  - Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) cause a variety of human diseases,
      ranging from acute to chronic and mild to severe. The absence of curative therapy
      results in lifelong carriage marked by recurrent outbreaks and allows
      transmission of the virus to uninfected individuals. Nonspecific lesions,
      variable presentation, and chronic carriage necessitate the use of different
      laboratory testing methods appropriate for each presentation. A thorough
      understanding of the performance characteristics and limitations of available
      tests is critical for selection of the appropriate test and interpretation of
      results. Clinical sensitivity, specificity, and selection of the appropriate
      methodology is paramount to avoid misdiagnosis and guide therapy. In this article
      we review the different methods for detection and typing of HSV, including light
      microscopy, culture, serology, and nucleic acid-based tests. We discuss the
      strengths and weaknesses of each method for diagnosing HSV infection, cite
      performance characteristics, and review appropriate clinical uses. 

PMID- 24131690
TI  - Disseminated adenovirus infection in cancer patients presenting with focal
      pulmonary consolidation.
AB  - We report disseminated adenovirus (ADV) infection in four adult cancer patients
      presenting with focal pulmonary consolidation. In all cases, ADV was recovered
      from respiratory specimens and ADV viremia (>1 * 10(5) copies/ml) was determined
      by a quantitative PCR assay. Despite antiviral therapy, 3 (75%) patients died.
      ADV should be considered as a possible cause of severe pneumonia in
      immunosuppressed patients. 

PMID- 24131691
TI  - Higher specificity of nucleic acid sequence-based amplification isothermal
      technology than of real-time PCR for quantification of HIV-1 RNA on dried blood
      spots.
AB  - Dried blood spots (DBS) are widely proposed as a plasma surrogate for monitoring
      antiretroviral treatment efficacy based on the HIV-1 RNA level (viral load [VL])
      in resource-limited settings. Interfering coamplification of cell-associated HIV
      1 DNA during reverse transcription (RT)-PCR can be avoided by using nucleic acid
      sequence-based amplification (NASBA) technology, which is based on an RNA
      template and isothermic conditions. We analyzed VL values obtained with DBS and
      plasma samples by comparing isothermic NASBA (NucliSENS EasyQ HIV-1 V2.0;
      bioMerieux) with real-time RT-PCR (Cobas TaqMan HIV-1 V2.0; Roche). Samples from
      197 HIV-1-infected patients were tested (non-B subtypes in 51% of the cases).
      Nucleic acid extractions were performed by use of NucliSENS EasyMAG (bioMerieux)
      and Cobas AmpliPrep (Roche) before the NASBA and RT-PCR quantifications,
      respectively. Both quantification assays have lower limits of detection of 20
      (1.3) and 800 (2.9) log10 copies/ml (log) in plasma and DBS, respectively. The
      mean (DBS minus plasma) differences were -0.39 and -0.46 log, respectively, for
      RT-PCR and NASBA. RT-PCR on DBS identified virological failure in 122 of 126
      patients (sensitivity, 97%) and viral suppression in 58 of 70 patients
      (specificity, 83%), yielding 12 false-positive results (median, 3.2 log). NASBA
      on DBS identified virological failure in 85 of 96 patients (sensitivity, 89%) and
      viral suppression in 95 of 97 patients (specificity, 98%) and yielded 2 false
      positive results (3.0 log for both). Both technologies detected HIV-1 RNA in DBS
      at a threshold of 800 copies/ml. This higher specificity of NASBA technology
      could avoid overestimation of poor compliance or the emergence of resistance when
      monitoring antiretroviral efficacy with the DBS method. 

PMID- 24131692
TI  - Gastroenteritis caused by the Cryptosporidium hedgehog genotype in an
      immunocompetent man.
AB  - The Cryptosporidium hedgehog genotype, which has been reported previously in
      hedgehogs and horses, was identified as the cause of the diarrheal disease
      cryptosporidiosis in an immunocompetent man in the Czech Republic. This is the
      first report of human illness caused by the Cryptosporidium hedgehog genotype. 

PMID- 24131693
TI  - Development of a capillary electrophoresis-based heteroduplex tracking assay to
      measure in-host genetic diversity of initial and recurrent Plasmodium vivax
      infections in Cambodia.
AB  - A heteroduplex tracking assay used to genotype Plasmodium vivax merozoite surface
      protein 1 was adapted to a capillary electrophoresis format, obviating the need
      for radiolabeled probes and allowing its use in settings where malaria is
      endemic. This new assay achieved good allelic discrimination and detected high
      multiplicities of infection in 63 P. vivax infections in Cambodia. More than half
      of the recurrent parasitemias sampled displayed identical or highly related
      genotypes compared to the initial genotype, suggesting that they represented
      relapses. 

PMID- 24131694
TI  - Molecular characterization of a catalase-negative methicillin-susceptible
      Staphylococcus aureus subsp. aureus strain collected from a patient with
      cutaneous abscess.
AB  - We describe a cutaneous abscess caused by catalase-negative methicillin
      susceptible Staphylococcus aureus subsp. aureus in a patient who was
      concomitantly colonized with virulent USA300 methicillin-resistant S. aureus
      (MRSA). Sequencing of the katA gene demonstrated a thymine insertion leading to a
      frameshift mutation and premature truncation of catalase to 21 amino acids. 

PMID- 24131695
TI  - Homology analysis of pathogenic Yersinia species Yersinia enterocolitica,
      Yersinia pseudotuberculosis, and Yersinia pestis based on multilocus sequence
      typing.
AB  - We developed a multilocus sequence typing (MLST) scheme and used it to study the
      population structure and evolutionary relationships of three pathogenic Yersinia
      species. MLST of these three Yersinia species showed a complex of two clusters,
      one composed of Yersinia pseudotuberculosis and Yersinia pestis and the other
      composed of Yersinia enterocolitica. Within the first cluster, the predominant Y.
      pestis sequence type 90 (ST90) was linked to Y. pseudotuberculosis ST43 by one
      locus difference, and 81.25% of the ST43 strains were from serotype O:1b,
      supporting the hypothesis that Y. pestis descended from the O:1b serotype of Y.
      pseudotuberculosis. We also found that the worldwide-prevalent serotypes O:1a,
      O:1b, and O:3 were predominated by specific STs. The second cluster consisted of
      pathogenic and nonpathogenic Y. enterocolitica strains, two of which may not have
      identical STs. The pathogenic Y. enterocolitica strains formed a relatively
      conserved group; most strains clustered within ST186 and ST187. Serotypes O:3,
      O:8, and O:9 were separated into three distinct blocks. Nonpathogenic Y.
      enterocolitica STs were more heterogeneous, reflecting genetic diversity through
      evolution. By providing a better and effective MLST procedure for use with the
      Yersinia community, valuable information and insights into the genetic
      evolutionary differences of these pathogens were obtained. 

PMID- 24131696
TI  - Performance of the Verigene Gram-positive blood culture assay for direct
      detection of Gram-positive organisms and resistance markers in a pediatric
      hospital.
AB  - The performance characteristics of the Verigene Gram-positive blood culture (BC
      GP) assay were evaluated in pediatric patients. Concordance of the BC-GP assay
      was 95.8%, with significant decreases in turnaround time for identification and
      resistance detection. BC-GP is highly accurate and can be integrated into the
      routine workflow of the microbiology laboratory. 

PMID- 24131697
TI  - Development and application of a multiplex PCR method for rapid differential
      detection of subgroup A, B, and J avian leukosis viruses.
AB  - Avian leukosis virus (ALV) subgroups A, B, and J are very common in poultry
      flocks and have caused serious economic losses in recent years. A multiplex PCR
      (mPCR) method for the detection of these three subgroups was developed and
      optimized in this study. We first designed a common forward primer, PF, and three
      downstream primers, AR, BR, and JR, which can amplify 715 bp for subgroup A, 515
      bp for subgroup B, and 422 bp for subgroup J simultaneously in one reaction. The
      mPCR method produced neither cross-reactions with other subgroups of ALVs nor
      nonspecific reactions with other common avian viruses. The detection limit of the
      mPCR was as low as 1 * 10(3) viral DNA copies of each of the three subgroups. In
      animal experiments, the mPCR detected ALVs 2 to 4 days earlier than did virus
      isolation from whole-blood samples and cloaca swabs. Furthermore, a total of 346
      clinical samples (including 127 tissue samples, 86 cloaca swabs, 59 albumen
      samples, and 74 whole-blood samples) from poultry flocks with suspected ALV
      infection were examined by mPCR, routine PCR, and virus isolation. The positive
      sample/total sample ratios for ALV-A, ALV-B, and ALV-J were 48% (166/346) as
      detected by mPCR and 48% (166/346) as detected by routine PCR. However, the
      positive sample/total sample ratio detected by virus isolation was 40% (138/346).
      The results of the mPCR and routine PCR were confirmed by sequencing the specific
      fragments. These results indicate that the mPCR method is rapid, specific,
      sensitive, and convenient for use in epidemiological studies of ALV, clinical
      detection of ALV, and ALV eradication programs. 

PMID- 24131699
TI  - Evaluation of agar-based medium with sheep sera for testing of drug
      susceptibility of Mycobacterium tuberculosis to Isoniazid, Rifampin, Ethambutol,
      and Streptomycin.
AB  - The performance of sheep sera instead of sheep blood in agar-based media was
      investigated for susceptibility testing of Mycobacterium tuberculosis against
      primary drugs. The levels of agreement between agar-based medium supplemented
      with sheep sera and the proportion method on Middlebrook 7H11 agar as the
      reference method for determining susceptibility to isoniazid (INH), rifampin
      (RIF), ethambutol (EMB), and streptomycin (STR) were 98.4, 98.4, 95.3, and 100%,
      respectively. 

PMID- 24131698
TI  - Evaluation of a multitarget real-time PCR assay for detection of Bordetella
      species during a pertussis outbreak in New Hampshire in 2011.
AB  - A multitarget real-time PCR assay with three targets, including insertion
      sequence 481 (IS481), IS1001, and an IS1001-like element, as well as pertussis
      toxin subunit S1 (ptxS1), for the detection of Bordetella species was evaluated
      during a pertussis outbreak. The sensitivity and specificity were 77 and 88%
      (PCR) and 66 and 100% (culture), respectively. All patients with an IS481 C(T) of
      <30 also tested positive by ptxS1 assay and were clinical pertussis cases. No
      patients with IS481 C(T) values of >=40 tested positive by culture. Therefore, we
      recommend that culture be performed only for specimens with IS481 C(T) values of
      30 <= CT <40.

PMID- 24131700
TI  - On the significance of germline cytogenetic rearrangements at MYCN locus in
      neuroblastoma.
AB  - BACKGROUND: MYCN oncogene amplification is the most important prognostic factor
      in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this
      locus but little is known about its constitutional aberrations and their
      potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR
      characterization of two patients with constitutional partial 2p trisomy including
      MYCN genomic region. RESULTS: One of the patients had congenital neuroblastoma
      and showed presence of minute areas of gains and losses within the common fragile
      site FRA2C at 2p24 encompassing MYCN. The link between 2p24 germline
      rearrangements and neuroblastoma development was reassessed by reviewing similar
      cases in the literature. CONCLUSIONS: It appears that constitutional
      rearrangements involving chromosome 2p24 may play role in NB development.

PMID- 24131701
TI  - An automated and standardized neural index to quantify patient-ventilator
      interaction.
AB  - INTRODUCTION: The aim of this study was to validate an automated, objective and
      standardized algorithm for quantifying and displaying patient-ventilator
      interaction. METHODS: Using a new method to detect patient-ventilator synchrony,
      the present study re-analyzed previously acquired and published data from 24
      mechanically ventilated adult patients (Colombo et al., Crit Care Med. 2011
      Nov;39(11):2452-7). Patient-ventilator interactions were evaluated by comparing
      ventilator pressure and diaphragm electrical activity (EAdi) waveforms, recorded
      during pressure support ventilation. The EAdi and ventilator pressure waveforms
      were analyzed for their timings (manually and automatically determined), and the
      error between the two waveforms was quantified. A new index of patient-ventilator
      interaction (NeuroSync index), which is standardized and automated, was validated
      and compared to manual analysis and previously published indices of asynchrony.
      RESULTS: The comparison of manual and automated detection methods produced high
      test-retest and inter-rater reliability (Intraclass correlation coefficient =
      0.95). The NeuroSync index increased the sensitivity of detecting dyssynchronies,
      compared to previously published indices, which were found to only detect
      asynchronies. CONCLUSION: The present study introduces an automated method and
      the NeuroSync index to determine patient-ventilator interaction with a more
      sensitive analysis method than those previously described. A dashboard-style of
      graphical display allows a rapid overview of patient-ventilator interaction and
      breathing pattern at the bedside.

PMID- 24131702
TI  - Initiation and continuation of randomized trials after the publication of a trial
      stopped early for benefit asking the same study question: STOPIT-3 study design.
AB  - BACKGROUND: Randomized control trials (RCTs) stopped early for benefit (truncated
      RCTs) are increasingly common and, on average, overestimate the relative
      magnitude of benefit by approximately 30%. Investigators stop trials early when
      they consider it is no longer ethical to enroll patients in a control group. The
      goal of this systematic review is to determine how investigators of ongoing or
      planned RCTs respond to the publication of a truncated RCT addressing a similar
      question. METHODS/DESIGN: We will conduct systematic reviews to update the
      searches of 210 truncated RCTs to identify similar trials ongoing at the time of
      publication, or started subsequently, to the truncated trials ('subsequent
      RCTs'). Reviewers will determine in duplicate the similarity between the
      truncated and subsequent trials. We will analyze the epidemiology, distribution,
      and predictors of subsequent RCTs. We will also contact authors of subsequent
      trials to determine reasons for beginning, continuing, or prematurely
      discontinuing their own trials, and the extent to which they rely on the
      estimates from truncated trials. DISCUSSION: To the extent that investigators
      begin or continue subsequent trials they implicitly disagree with the decision to
      stop the truncated RCT because of an ethical mandate to administer the
      experimental treatment. The results of this study will help guide future
      decisions about when to stop RCTs early for benefit.

PMID- 24131703
TI  - Age-dependent patterns of bovine tuberculosis in cattle.
AB  - Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting
      cattle industries in both industrialised and pre-industrialised countries. Like
      TB in other mammals, infection is life long and, if undiagnosed, may progress to
      disease years after exposure. The risk of disease in humans is highly age
      dependent, however in cattle, age-dependent risks have yet to be quantified,
      largely due to insufficient data and limited diagnostics. Here, we estimate age
      specific reactor rates in Great Britain by combining herd-level testing data with
      spatial movement data from the Cattle Tracing System (CTS). Using a catalytic
      model, we find strong age dependencies in infection risk and that the probability
      of detecting infection increases with age. Between 2004 and 2009, infection
      incidence in cattle fluctuated around 1%. Age-specific incidence increased
      monotonically until 24-36 months, with cattle aged between 12 and 36 months
      experiencing the highest rates of infection. Beef and dairy cattle under 24
      months experienced similar infection risks, however major differences occurred in
      older ages. The average reproductive number in cattle was greater than 1 for the
      years 2004-2009. These methods reveal a consistent pattern of BTB rates with age,
      across different population structures and testing patterns. The results provide
      practical insights into BTB epidemiology and control, suggesting that targeting a
      mass control programme at cattle between 12 and 36 months could be beneficial.

PMID- 24131706
TI  - Mortality from uveal melanoma treated by enucleation --a 16-year survey in
      Taiwan.

PMID- 24131707
TI  - Chronic low back pain patient groups in primary care--a cross sectional cluster
      analysis.
AB  - BACKGROUND: Due to the heterogeneous nature of chronic low back pain (CLBP), it
      is necessary to identify patient groups and evaluate treatments within these
      groups. We aimed to identify groups of patients with CLBP in the primary care
      setting. METHODS: We performed a k-means cluster analysis on a large data set (n
      = 634) of primary care patients with CLBP. Variables of sociodemographic data,
      pain characteristics, psychological status (i.e., depression, anxiety,
      somatization), and the patient resources of resilience and coping strategies were
      included. RESULTS: We found three clusters that can be characterized as
      "pensioners with age-associated pain caused by degenerative diseases", "middle
      aged patients with high mental distress and poor coping resources", and "middle
      aged patients who are less pain-affected and better positioned with regard to
      their mental health". CONCLUSIONS: Our results supported current knowledge
      concerning groups of CLBP patients in primary care. In particular, we identified
      a group that was most disabled and distressed, and which was mainly characterized
      by psychological variables. As shown in our study, pain-related coping strategies
      and resilience were low in these patients and might be addressed in
      differentiating treatment strategies. Future studies should focus on the
      identification of this group in order to achieve effective treatment allocation.
      TRIAL REGISTRATION: German Clinical Trial Register DRKS00003123.

PMID- 24131708
TI  - Management of postpartum depression.
AB  - The mainstays of treatment for peripartum depression are psychotherapy and
      antidepressant medications. More research is needed to understand which
      treatments are safe, preferable, and effective. Postpartum depression, now termed
      peripartum depression by the DSM-V, is one of the most common complications in
      the postpartum period and has potentially significant negative consequences for
      mothers and their families. This article highlights common clinical challenges in
      the treatment of peripartum depression and reviews the evidence for currently
      available treatment options. Psychotherapy is the first-line treatment option for
      women with mild to moderate peripartum depression. Antidepressant medication in
      combination with therapy is recommended for women with moderate to severe
      depression. Although pooled case reports and small controlled studies have
      demonstrated undetectable infant serum levels and no short-term adverse events in
      infants of mothers breastfeeding while taking sertraline (Zoloft) and paroxetine
      (Paxil), further research is needed including larger samples and long-term follow
      up of infants exposed to antidepressants via breastfeeding controlling for
      maternal depression. Pharmacologic treatment recommendations for women who are
      lactating must include discussion with the patient regarding the benefits of
      breastfeeding, risks of antidepressant use during lactation, and risks of
      untreated illness. There is a growing evidence base for nonpharmacologic
      interventions including repetitive transcranial magnetic stimulation, which may
      offer an attractive option for women who wish to continue to breastfeed and are
      concerned about their infants being exposed to medication. Among severe cases of
      peripartum depression with psychosis, referral to a psychiatrist or psychiatric
      advanced practice registered nurse is warranted. Suicidal or homicidal ideation
      with a desire, intent, or plan to harm oneself or anyone else, including the
      infant, is a psychiatric emergency, and an evaluation by a mental health
      professional should be conducted immediately. Peripartum depression treatment
      research is limited by small sample sizes and few controlled studies. Much work
      is still needed to better understand which treatments women prefer and are the
      most effective in ameliorating the symptoms and disease burden associated with
      peripartum depression. 

PMID- 24131709
TI  - Chronic joint disease caused by persistent Chikungunya virus infection is
      controlled by the adaptive immune response.
AB  - Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes
      incapacitating disease in humans characterized by intense joint pain that can
      persist for weeks, months, or even years. Although there is some evidence of
      persistent CHIKV infection in humans suffering from chronic rheumatologic disease
      symptoms, little is known about chronic disease pathogenesis, and no specific
      therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of
      chronic CHIKV-induced disease, we utilized a mouse model and defined the duration
      of CHIKV infection in tissues and the associated histopathological changes.
      Although CHIKV RNA was readily detectable in a variety of tissues very early
      after infection, CHIKV RNA persisted specifically in joint-associated tissues for
      at least 16 weeks. Inoculation of Rag1(-/-) mice, which lack T and B cells,
      resulted in higher viral levels in a variety of tissues, suggesting that adaptive
      immunity controls the tissue specificity and persistence of CHIKV infection. The
      presence of CHIKV RNA in tissues of wild-type and Rag1(-/-) mice was associated
      with histopathological evidence of synovitis, arthritis, and tendonitis; thus,
      CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune
      responses. Finally, we show that prophylactic administration of CHIKV-specific
      monoclonal antibodies prevented the establishment of CHIKV persistence, whereas
      therapeutic administration had tissue-specific efficacy. These findings suggest
      that chronic musculoskeletal tissue pathology is caused by persistent CHIKV
      infection and controlled by adaptive immune responses. Our results have
      significant implications for the development of strategies to mitigate the
      disease burden associated with CHIKV infection in humans. 

PMID- 24131710
TI  - Alternative reassortment events leading to transmissible H9N1 influenza viruses
      in the ferret model.
AB  - Influenza A H9N2 viruses are common poultry pathogens that occasionally infect
      swine and humans. It has been shown previously with H9N2 viruses that
      reassortment can generate novel viruses with increased transmissibility. Here, we
      demonstrate the modeling power of a novel transfection-based inoculation system
      to select reassortant viruses under in vivo selective pressure. Plasmids
      containing the genes from an H9N2 virus and a pandemic H1N1 (pH1N1) virus were
      transfected into HEK 293T cells to potentially generate the full panel of
      possible H9 reassortants. These cells were then used to inoculate ferrets, and
      the population dynamics were studied. Two respiratory-droplet-transmissible H9N1
      viruses were selected by this method, indicating a selective pressure in ferrets
      for the novel combination of surface genes. These results show that a
      transfection-based inoculation system is a fast and efficient method to model
      reassortment and highlight the risk of reassortment between H9N2 and pH1N1
      viruses. 

PMID- 24131711
TI  - Characterization of the envelope glycoprotein of a novel filovirus, lloviu virus.
AB  - Lloviu virus (LLOV), a novel filovirus detected in bats, is phylogenetically
      distinct from viruses in the genera Ebolavirus and Marburgvirus in the family
      Filoviridae. While filoviruses are known to cause severe hemorrhagic fever in
      humans and/or nonhuman primates, LLOV is biologically uncharacterized, since
      infectious LLOV has never been isolated. To examine the properties of LLOV, we
      characterized its envelope glycoprotein (GP), which likely plays a key role in
      viral tropism and pathogenicity. We first found that LLOV GP principally has the
      same primary structure as the other filovirus GPs. Similar to the other
      filoviruses, virus-like particles (VLPs) produced by transient expression of LLOV
      GP, matrix protein, and nucleoprotein in 293T cells had densely arrayed GP spikes
      on a filamentous particle. Mouse antiserum to LLOV VLP was barely cross-reactive
      to viruses of the other genera, indicating that LLOV is serologically distinct
      from the other known filoviruses. For functional study of LLOV GP, we utilized a
      vesicular stomatitis virus (VSV) pseudotype system and found that LLOV GP
      requires low endosomal pH and cathepsin L, and that human C-type lectins act as
      attachment factors for LLOV entry into cells. Interestingly, LLOV GP-pseudotyped
      VSV infected particular bat cell lines more efficiently than viruses bearing
      other filovirus GPs. These results suggest that LLOV GP mediates cellular entry
      in a manner similar to that of the other filoviruses while showing preferential
      tropism for some bat cells. 

PMID- 24131712
TI  - Chimeric virus-like particle vaccines displaying conserved enterovirus 71
      epitopes elicit protective neutralizing antibodies in mice through divergent
      mechanisms.
AB  - Enterovirus 71 (EV71) is a major causative agent of hand, food, and mouth
      disease, which frequently occurs in young children. Since there are 11
      subgenotypes (A, B1 to B5, and C1 to C5) within EV71, an EV71 vaccine capable of
      protecting against all of these subgenotypes is desirable. We report here the
      vaccine potential and protective mechanism of two chimeric virus-like particles
      (VLPs) presenting conserved neutralizing epitopes of EV71. We show that fusions
      of hepatitis B core antigen (HBc) with the SP55 or SP70 epitope of EV71,
      designated HBcSP55 and HBcSP70, respectively, can be rapidly generated and self
      assembled into VLPs with the epitopes displayed on the surface. Immunization with
      the chimeric VLPs induced carrier- and epitope-specific antibody responses in
      mice. Anti-HBcSP55 and anti-HBcSP70 sera, but not anti-HBc sera, were able to
      neutralize in vitro multiple genotypes and strains of EV71. Importantly, passive
      immunization with anti-HBcSP55 or anti-HBcSP70 sera protected neonatal mice
      against lethal EV71 infections. Interestingly, anti-HBcSP70 sera could inhibit
      EV71 attachment to susceptible cells, whereas anti-HBcSP55 sera could not.
      However, both antisera were able to neutralize EV71 infection in vitro at the
      postattachment stage. The divergent mechanism of neutralization and protection
      conferred by anti-SP70 and anti-SP55 sera is in part attributed to their
      respective ability to bind authentic viral particles. Collectively, our study not
      only demonstrates that chimeric VLPs displaying the SP55 and SP70 epitopes are
      promising candidates for a broad-spectrum EV71 vaccine but also reveals distinct
      mechanisms of neutralization by the SP55- and SP70-targeted antibodies. 

PMID- 24131713
TI  - Rotavirus NSP1 protein inhibits interferon-mediated STAT1 activation.
AB  - Rotavirus (RV) replicates efficiently in intestinal epithelial cells (IECs) in
      vivo despite the activation of a local host interferon (IFN) response.
      Previously, we demonstrated that homologous RV efficiently inhibits IFN induction
      in single infected and bystander villous IECs in vivo. Paradoxically, RV also
      induces significant type I IFN expression in the intestinal hematopoietic cell
      compartment in a relatively replication-independent manner. This suggests that RV
      replication and spread in IECs must occur despite exogenous stimulation of the
      STAT1-mediated IFN signaling pathway. Here we report that RV inhibits IFN
      mediated STAT1 tyrosine 701 phosphorylation in human IECs in vitro and identify
      RV NSP1 as a direct inhibitor of the pathway. Infection of human HT29 IECs with
      simian (RRV) or porcine (SB1A or OSU) RV strains, which inhibit IFN induction by
      targeting either IFN regulatory factor 3 (IRF3) or NF-kappaB, respectively,
      resulted in similar regulation of IFN secretion. By flow cytometric analysis at
      early times during infection, neither RRV nor SB1A effectively inhibited the
      activation of Y701-STAT1 in response to exogenously added IFN. However, at later
      times during infection, both RV strains efficiently inhibited IFN-mediated STAT1
      activation within virus-infected cells, indicating that RV encodes inhibitors of
      IFN signaling targeting STAT1 phosphorylation. Expression of RV NSP1 in the
      absence of other viral proteins resulted in blockage of exogenous IFN-mediated
      STAT1 phosphorylation, and this function was conserved in NSP1 from simian,
      bovine, and murine RV strains. Analysis of NSP1 determinants responsible for the
      inhibition of IFN induction and signaling pathways revealed that these
      determinants are encoded on discrete domains of NSP1. Finally, we observed that
      at later times during infection with SB1A, there was almost complete inhibition
      of IFN-mediated Y701-STAT1 in bystander cells staining negative for viral
      antigen. This property segregated with the NSP1 gene and was observed in a simian
      SA11 monoreassortant that encoded porcine OSU NSP1 but not in wild-type SA11 or a
      reassortant encoding simian RRV NSP1. 

PMID- 24131714
TI  - Functional characterization of bovine viral diarrhea virus nonstructural protein
      5A by reverse genetic analysis and live cell imaging.
AB  - Nonstructural protein 5A (NS5A) of bovine viral diarrhea virus (BVDV) is a
      hydrophilic phosphoprotein with RNA binding activity and a critical component of
      the viral replicase. In silico analysis suggests that NS5A encompasses three
      domains interconnected by two low-complexity sequences (LCSs). While domain I
      harbors two functional determinants, an N-terminal amphipathic helix important
      for membrane association, and a Zn-binding site essential for RNA replication,
      the structure and function of the C-terminal half of NS5A are still ill defined.
      In this study, we introduced a panel of 10 amino acid deletions covering the C
      terminal half of NS5A. In the context of a highly efficient monocistronic
      replicon, deletions in LCS I and the N-terminal part of domain II, as well as in
      domain III, were tolerated with regard to RNA replication. When introduced into a
      bicistronic replicon, only deletions in LCS I and the N-terminal part of domain
      II were tolerated. In the context of the viral full-length genome, these
      mutations allowed residual virion morphogenesis. Based on these data, a
      functional monocistronic BVDV replicon coding for an NS5A variant with an
      insertion of the fluorescent protein mCherry was constructed. Live cell imaging
      demonstrated that a fraction of NS5A-mCherry localizes to the surface of lipid
      droplets. Taken together, this study provides novel insights into the functions
      of BVDV NS5A. Moreover, we established the first pestiviral replicon expressing
      fluorescent NS5A-mCherry to directly visualize functional viral replication
      complexes by live cell imaging. 

PMID- 24131715
TI  - Transcription of true late (gamma2) cytomegalovirus genes requires UL92 function
      that is conserved among beta- and gammaherpesviruses.
AB  - Human cytomegalovirus-encoded UL92 plays an essential role in viral replication
      that has not been resolved. We show here that this gene controls the accumulation
      of true late (gamma2) viral transcripts, a property shared with several other
      recently evaluated genes (UL79, UL87, UL91, and UL95) conserved among beta- and
      gammaherpesviruses. When the UL92 mutant virus was evaluated, function was fully
      complemented by either the natural protein or the homologous Rh127 protein from
      rhesus cytomegalovirus. N-terminal epitope-tagged UL92 protein is functional,
      follows complex early-late expression kinetics, and localizes in the nucleus
      within viral replication compartments. UL92 severely impacts the late (72-h
      postinfection) expression of nine genes encoding virion proteins (UL32, UL55,
      UL73, UL75, UL80, UL86, UL99, and UL115), as well as UL91 and itself, but does
      not influence the levels of UL44, UL82, or UL83 accumulation. Although viral DNA
      is made at normal levels, viral capsid accumulation in the nucleus is severely
      compromised in UL92 mutant virus-infected cells, and mature virions are not
      observed in the cytoplasm. Taken together, UL92 is a key regulator of late viral
      gene expression, apparently functioning with four other beta- or gammaherpesvirus
      gene products in a pattern that appears reminiscent of gene regulation in T4 DNA
      bacteriophage. 

PMID- 24131716
TI  - Elucidation of the block to herpes simplex virus egress in the absence of
      tegument protein UL16 reveals a novel interaction with VP22.
AB  - UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among
      all members of the Herpesviridae, but its function is poorly understood. Previous
      studies revealed that UL16 is associated with capsids in the cytoplasm and
      interacts with the membrane protein UL11, which suggested a "bridging" function
      during cytoplasmic envelopment, but this conjecture has not been tested. To gain
      further insight, cells infected with UL16-null mutants were examined by electron
      microscopy. No defects in the transport of capsids to cytoplasmic membranes were
      observed, but the wrapping of capsids with membranes was delayed. Moreover,
      clusters of cytoplasmic capsids were often observed, but only near membranes,
      where they were wrapped to produce multiple capsids within a single envelope.
      Normal virion production was restored when UL16 was expressed either by
      complementing cells or from a novel position in the HSV genome. When the
      composition of the UL16-null viruses was analyzed, a reduction in the packaging
      of glycoprotein E (gE) was observed, which was not surprising, since it has been
      reported that UL16 interacts with this glycoprotein. However, levels of the
      tegument protein VP22 were also dramatically reduced in virions, even though this
      gE-binding protein has been shown not to depend on its membrane partner for
      packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in
      the absence of other viral proteins. These results extend the UL16 interaction
      network beyond its previously identified binding partners to include VP22 and
      provide evidence that UL16 plays an important function at the membrane during
      virion production. 

PMID- 24131717
TI  - Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene
      expression.
AB  - In this study, we report that murine cytomegalovirus (MCMV) protein pM92
      regulates viral late gene expression during virus infection. Previously, we have
      shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79
      are required for late viral gene transcription. Identification of additional
      factors involved is critical to dissecting the mechanism of this regulation. We
      show here that pM92 accumulated abundantly at late times of infection in a DNA
      synthesis-dependent manner and localized to nuclear viral replication
      compartments. To investigate the role of pM92, we constructed a recombinant virus
      SMin92, in which pM92 expression was disrupted by an insertional/frameshift
      mutation. During infection, SMin92 accumulated representative viral immediate
      early gene products, early gene products, and viral DNA sufficiently but had
      severe reduction in the accumulation of late gene products and was thus unable to
      produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis
      revealed an interaction between pM92 and pM79, as well as between their HCMV
      homologues pUL92 and pUL79. Importantly, we showed that the growth defect of
      pUL92-deficient HCMV could be rescued in trans by pM92. This study indicates that
      pM92 is an additional viral regulator of late gene expression, that these
      regulators (represented by pM92 and pM79) may need to complex with each other for
      their activity, and that pM92 and pUL92 share a conserved function in CMV
      infection. pM92 represents a potential new target for therapeutic intervention in
      CMV disease, and a gateway into studying a largely uncharted viral process that
      is critical to the viral life cycle. 

PMID- 24131718
TI  - Comparative virus replication and host innate responses in human cells infected
      with three prevalent clades (2.3.4, 2.3.2, and 7) of highly pathogenic avian
      influenza H5N1 viruses.
AB  - Highly pathogenic avian influenza H5N1 virus clades 2.3.4, 2.3.2, and 7 are the
      dominant cocirculating H5N1 viruses in poultry in China. However, humans appear
      to be clinically susceptible mostly to the 2.3.4 virus clade. Here, we
      demonstrated that A549 cells and human macrophages infected with clade 2.3.4
      viruses produced significantly more viruses than those infected with the other
      two clades. Likewise, clade 2.3.4-infected macrophages caused the most severe
      cellular damage and strongest proinflammatory response. 

PMID- 24131719
TI  - Both HLA-B*57 and plasma HIV RNA levels contribute to the HIV-specific CD8+ T
      cell response in HIV controllers.
AB  - CD8(+) T cell responses are thought to play an important role during HIV
      infection, particularly in HIV controllers (HIC) in whom viral replication is
      spontaneously controlled without any treatment. We have demonstrated that CD8(+)
      T cells from these subjects are able to suppress viral replication in vitro. In
      parallel, HIV-specific CD8(+) responses were shown to be strong and of high
      quality, with proliferative abilities and cytotoxic capacities, in HIC. The HLA
      B*57 allele, which is associated with a better clinical outcome in HIV infection,
      is overrepresented in HIC. However, we showed that these patients constitute a
      heterogeneous group that includes subjects who present weak suppression of viral
      replication in vitro and HIV-specific responses. We performed an extensive study
      of 101 HIC (49 HLA-B*57(+) and 52 HLA-B*57(-)) to determine the impact of HLA
      B*57 on the HIV-specific CD8(+) response. The HLA-B*57-restricted response
      displayed better qualitative features, such as higher functional avidity, higher
      proliferation capacity, and a higher level of cytokine production, than responses
      not restricted by HLA-B*57. However, the highest frequencies of HIV-specific
      CD8(+) T cells were observed only in a subset of HLA-B*57(+) subjects. They were
      tightly associated with the ability to suppress viral replication in vitro. In
      contrast, the subset of HLA-B*57(+) subjects with a weak ability to suppress
      viral replication had significantly lower ultrasensitive viral loads than all the
      other groups of controllers. In conclusion, both HLA-B*57 and the amount of
      ultrasensitive viral load seem to play a role in HIV-specific CD8(+) T cell
      responses in HIC. 

PMID- 24131720
TI  - The selection of low envelope glycoprotein reactivity to soluble CD4 and cold
      during simian-human immunodeficiency virus infection of rhesus macaques.
AB  - Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human
      immunodeficiency virus type 1 (HIV-1) Env to change conformation from the
      metastable unliganded state in response to the binding of ligands (antibodies and
      soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that
      favor in vivo persistence, we inoculated rhesus macaques with three closely
      related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in
      ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by
      antibodies equivalently and thus were similar in ERantibody. All three SHIVs
      achieved high levels of acute viremia in the monkeys without alteration of their
      Env sequences, indicating that neither ERcold nor ERsCD4 significantly influences
      the establishment of infection. Between 14 and 100 days following infection,
      viruses with high ERcold and ERsCD4 were counterselected. Remarkably, the virus
      variant with low ERcold and low ERsCD4 did not elicit a neutralizing antibody
      response against the infecting virus, despite the generation of high levels of
      anti-Env antibodies in the infected monkeys. All viruses that achieved persistent
      viremia escaped from any autologous neutralizing antibodies and exhibited low
      ERcold and low ERsCD4. One set of gp120 changes determined the decrease in ERcold
      and ERsCD4, and a different set of gp120 changes determined resistance to
      autologous neutralizing antibodies. Each set of changes contributed to a
      reduction in Env-mediated entry. During infection of monkeys, any Env replication
      fitness costs associated with decreases in ERcold and ERsCD4 may be offset by
      minimizing the elicitation of autologous neutralizing antibodies. 

PMID- 24131721
TI  - Residues Arg703, Asp777, and Arg781 of the RNase H domain of hepatitis B virus
      polymerase are critical for viral DNA synthesis.
AB  - Hepatitis B virus (HBV) synthesizes its DNA genome through reverse transcription,
      which is catalyzed by viral polymerase (Pol). Previous studies suggested that the
      RNase H domain of hepadnaviral Pol may contribute to multiple steps of the viral
      genome replication, such as RNA encapsidation and viral DNA synthesis. However,
      specific residues of the RNase H domain that contribute to viral reverse
      transcription have not been determined. Therefore, we employed charged-to-alanine
      scanning mutagenesis to generate a set of single-substitution mutants of the
      RNase H domain and then analyzed their ability to support viral reverse
      transcription. Southern blot analysis showed that three mutants (R703A, D777A,
      and R781A mutants) yielded significantly reduced amounts of viral DNAs. However,
      none of these mutants were defective in RNA encapsidation. The data indicated
      that in the R703A and D777A mutants, minus-strand DNA synthesis was incomplete
      due to loss of catalytic activity of RNase H. In contrast, in the R781A mutant,
      the minus-strand DNA synthesis was near complete to some extent, while the plus
      strand DNA synthesis (i.e., relaxed circular DNA) was severely impaired due to
      the defect in RNase H activity. Overall, our analysis revealed that three charged
      residues of the HBV Pol RNase H domain contribute to the catalysis of RNase H in
      removing the RNA template, but not in the RNA encapsidation. 

PMID- 24131722
TI  - Characterization of a novel betacoronavirus related to middle East respiratory
      syndrome coronavirus in European hedgehogs.
AB  - Bats are known to host viruses closely related to important human coronaviruses
      (HCoVs), such as HCoV-229E, severe-acute respiratory syndrome coronavirus (SARS
      CoV), and Middle East respiratory syndrome CoV (MERS-CoV). As RNA viruses may
      coevolve with their hosts, we sought to investigate the closest sister taxon to
      bats, the Eulipotyphla, and screened European hedgehogs (Erinaceus europaeus)
      from Germany for CoV by nested reverse transcriptase PCR. A novel betacoronavirus
      species in a phylogenetic sister relationship to MERS-CoV and clade c bat CoVs
      was detected and characterized on the whole-genome level. A total of 58.9% of
      hedgehog fecal specimens were positive for the novel CoV (EriCoV) at 7.9 log10
      mean RNA copies per ml. EriCoV RNA concentrations were higher in the intestine
      than in other solid organs, blood, or urine. Detailed analyses of the full
      hedgehog intestine showed the highest EriCoV concentrations in lower
      gastrointestinal tract specimens, compatible with viral replication in the lower
      intestine and fecal-oral transmission. Thirteen of 27 (48.2%) hedgehog sera
      contained non-neutralizing antibodies against MERS-CoV. The animal origins of
      this betacoronavirus clade that includes MERS-CoV may thus include both bat and
      nonbat hosts. 

PMID- 24131723
TI  - Mosquito saliva serine protease enhances dissemination of dengue virus into the
      mammalian host.
AB  - Dengue virus (DENV), a flavivirus of global importance, is transmitted to humans
      by mosquitoes. In this study, we developed in vitro and in vivo models of saliva
      mediated enhancement of DENV infectivity. Serine protease activity in Aedes
      aegypti saliva augmented virus infectivity in vitro by proteolyzing extracellular
      matrix proteins, thereby increasing viral attachment to heparan sulfate
      proteoglycans and inducing cell migration. A serine protease inhibitor reduced
      saliva-mediated enhancement of DENV in vitro and in vivo, marked by a 100-fold
      reduction in DENV load in murine lymph nodes. A saliva-mediated infectivity
      enhancement screen of fractionated salivary gland extracts identified serine
      protease CLIPA3 as a putative cofactor, and short interfering RNA knockdown of
      CLIPA3 in mosquitoes demonstrated its role in influencing DENV infectivity.
      Molecules in mosquito saliva that facilitate viral infectivity in the vertebrate
      host provide novel targets that may aid in the prevention of disease. 

PMID- 24131724
TI  - Crystal structures of beta- and gammaretrovirus fusion proteins reveal a role for
      electrostatic stapling in viral entry.
AB  - Membrane fusion is a key step in the life cycle of all envelope viruses, but this
      process is energetically unfavorable; the transmembrane fusion subunit (TM) of
      the virion-attached glycoprotein actively catalyzes the membrane merger process.
      Retroviral glycoproteins are the prototypical system to study pH-independent
      viral entry. In this study, we determined crystal structures of extramembrane
      regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine
      leukemia virus-related virus (XMRV) at 1.7-A and 2.2-A resolution, respectively.
      The structures are comprised of a trimer of hairpins that is characteristic of
      class I viral fusion proteins and now completes a structural library of
      retroviral fusion proteins. Our results allowed us to identify a series of intra-
      and interchain electrostatic interactions in the heptad repeat and chain reversal
      regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations
      significantly destabilize the postfusion six-helix bundle and abrogate retroviral
      infection, demonstrating that electrostatic stapling of the fusion subunit is
      essential for viral entry. Our data indicate that salt bridges are a major
      stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key
      energetics for viral and host membrane fusion. 

PMID- 24131725
TI  - NADPH oxidase mediates the expression of MMP-9 in cerebral tissue after ischemia
      reperfusion damage.
AB  - Oxygen free radicals and their reactive lipid peroxidation are known to be
      elements promoting ischemia-reperfusion damage. NADPH oxidase is a major factor
      in peroxide production. Excessive production of oxygen free radicals is
      considered as an important mechanism in the expression of matrix
      metalloproteinase (MMP)-9 and in damage to the blood-brain barrier (BBB). In this
      study, we evaluated changes in the expression of the NADPH oxidase catalytic
      subunit gp91(phox) and oxidase activity, as well as the involvement of NADPH
      oxidase catalysis in the expression of MMP-9 in cerebral tissue after ischemia
      reperfusion damage. A middle cerebral artery occlusion (MCAO) model was
      established using male Sprague-Dawley (SD) rats. Brain tissue was isolated for
      triphenyltetrazolium chloride (TTC) staining, gp91(phox) mRNA quantitative PCR
      analysis, western blot analysis, NADPH oxidase activity determination
      (detection), and MMP-9 gelatin zymography analysis. In the MCAO rats, gp91(phox)
      and MMP-9 expression was upregulated in the ischemic hemisphere of the brain
      tissue after 90 minutes of MCAO with 22.5 hours of reperfusion. Inhibition of
      NADPH oxidase with apocynin reduced the increase in MMP-9. These results suggest
      that NADPH oxidase is a major precipitating factor for the expression of MMP-9 in
      the ischemic brain tissue. 

PMID- 24131726
TI  - Equine deep stromal abscesses (51 cases - 2004-2009)--Part 1: the clinical
      aspects with attention to the duration of the corneal disease, treatment history,
      clinical appearance, and microbiology results.
AB  - OBJECTIVE: To study the equine deep stromal abscesses (DSA) with focus on the
      duration of the corneal disease, medical treatment, season of presentation,
      clinical appearance, and the degree of corneal vascularization. MATERIAL AND
      METHODS: Equine DSA diagnosed, biopsied, and surgically treated at the University
      of Florida Veterinary Medical Center (UFVMC) from 2004 to 2009 were identified.
      The medical record, clinical photographic images, and microbiology results for
      each case were evaluated. Frequency and prevalence calculation as well as
      qualitative data analysis was performed for clinical and microbiological data.
      RESULTS: Fifty-one equine DSA were included in the study. Spring (March, April,
      May; 33.4%) and winter (December, January, February; 31.4%) were the most common
      seasons for DSA presentation. The 51 cases were divided into four categories of
      focal opacity from their clinical appearance: focal yellow (45.2%), focal white
      (23.5%), diffuse yellow/white (23.5%), and focal pink (7.8%). 5.9% of the DSA (n
      = 3) were culture positive for fungal growth, whereas 17.6% were positive for
      bacterial growth (n = 9). No association between short-/long-term systemically
      administered NSAID treatment and the corneal vascular response to the corneal
      lesion could be appreciated. CONCLUSION: Equine DSA most often present in the
      spring and winter in the subtropical environment of the state of Florida (USA).
      The clinical appearance may have a connection with the etiology and pathogenesis
      of the equine DSA. No connection between short- or long-term systemically
      administered NSAID and the degree of corneal vascularization of the DSA was
      noted.

PMID- 24131727
TI  - The plantar fat pad and the diabetic foot--a review.
AB  - There has been much debate concerning the pathologic consequences of diabetes on
      the plantar fat pad and its subsequent association with the development of a foot
      ulcer. This review article documents two theories regarding pathophysiology in
      diabetic foot ulcer formation as they are related to the plantar fat pad and
      discusses current treatment options for this pathophysiological phenomenon.
      Traditionally, fat pad atrophy in diabetic patients was thought to result as an
      irregular arrangement of collagen fibrils within the septal walls as a result of
      glycation as well as diminishing adipocyte size due to thickened septal walls.
      Contrary to this traditional theory, a model depicting distal fat pad migration
      from under the metatarsal heads has been described in the diabetic patient. Such
      pad migration renders the metatarsal heads vulnerable to increased pressure,
      which, in turn, predisposes to foot ulceration. This migratory fat pad theory
      plays a significant role in approaches to the prevention of diabetic foot
      ulceration and subsequent amputation. Various methods of fat pad supplementation
      and claw toe management are impacted by the pathophysiological changes described
      and new avenues of therapy may be based on these changes. 

PMID- 24131728
TI  - A giant pregnancy-associated intra-abdominal desmoid tumour: not necessarily a
      contraindication for subsequent pregnancy.
AB  - Desmoid tumours are rare mesenchymal tumours, often locally invasive and
      characteristically associated with a high local recurrence rate after resection.
      A potential aetiological role for female hormones is indicated. Pregnancy
      associated desmoid tumours are almost exclusively located in the abdominal wall.
      An essential issue is how to counsel women who have had a pregnancy-associated
      desmoid tumour and subsequently wish to bear a child. A considerably rare case of
      a patient with a resection of a giant pregnancy-associated, 33 cm in diameter,
      intra-abdominal desmoid tumour is presented. After a subsequent pregnancy, the
      patient delivered healthy twins 26 months later. Fifty-four months after
      treatment, there are no signs of recurrent or second desmoid tumour. Although
      rarely located in the abdomen, pregnancy-associated desmoid tumours should be
      included in the differential diagnosis of intra-abdominal tumours detected during
      or shortly after pregnancy. Based on this case and a few others reported in the
      literature, subsequent pregnancy does not necessarily seem to be a risk factor
      for recurrent or new disease.

PMID- 24131729
TI  - Health literacy, socioeconomic status and self-rated health in Japan.
AB  - Health literacy (HL) is a key determinant of health in a contemporary society
      characterized by abundant information. Previous studies have suggested that basic
      or functional HL is positively associated with health, whereas evidences on the
      association between health and communicative/critical HL are scarce. Furthermore,
      confounding by socioeconomic status on HL-health association has been poorly
      tested. Using cross-sectional data from a nationally representative community
      based survey in Japan, we investigated whether communicative/critical HL is
      associated with self-rated health independent of socioeconomic status. A total of
      1237 subjects participated in this study; the response rate was 62%. To measure
      communicative/critical HL, we used three questions assessing the respondents'
      ability to select, to communicate to others and to evaluate specific health
      related information. Potential confounders included demographic factors,
      household income, employment status, and educational attainment. A multivariate
      model revealed that good self-reported health was significantly associated with
      younger age [odds ratio (OR), 0.99; 95% confidence interval (CI), 0.97-0.99],
      employment (OR, 2.89; 95% CI, 1.06-7.88) and higher communicative/critical HL
      scores (OR 2.75; 95%CI, 1.93-3.90). Respondents with lower education were likely
      to have poorer communicative/critical HL. These results imply that to close the
      health gap, policy interventions should focus on the promotion of HL among
      deprived sociodemographic groups. 

PMID- 24131730
TI  - In vivo confocal microscopy in goldenhar syndrome: a case report.
AB  - BACKGROUND: Goldenhar Syndrome is characterized by malformations of multiple
      anatomical districts. Between these, bulbar dermoids are common and represent a
      significant clinical problem as they can affect both ocular function and
      aesthetic comfort.Histologic characterization of dermoids has been extensively
      performed; however, no reports exist describing in vivo confocal microscopy
      (IVCM) of these lesions. We aimed to (i) describe the in vivo confocal morphology
      of limbal dermoids in Goldenhar syndrome and (ii) compare these findings with
      standard light microscopy. CASE PRESENTATION: A 15-year-old Caucasian female
      affected by Goldenhar Syndrome showed a left, infero-temporal, limbal
      neoformation, with extension to the left orbital region. Prior to surgical
      removal, IVCM was performed with the Heidelberg Retina Tomograph II, Cornea
      Module, using the "section" modality. The IVCM sections showed structures
      resembling corneal epithelium and vascular structures. Surgical removal of the
      lesion was decided as it caused poor eyelid closure. After surgical removal,
      sectioning and standard optical microscopy were performed. The comparison between
      IVCM imaging and standard microscopy sections were highly correlated in the
      detection of the pilar and vascular structures. CONCLUSIONS: This study showed
      that IVCM may be a useful technique to study limbal dermoids, given its ability
      to detect typical microscopic features and its comparability to optical
      microscopy, which is the current standard.

PMID- 24131731
TI  - Phytotoxins produced by plant pathogenic Streptomyces species.
AB  - Streptomyces is a large genus consisting of soil-dwelling, filamentous bacteria
      that are best known for their capability of producing a vast array of medically
      and agriculturally useful secondary metabolites. In addition, a small number of
      Streptomyces spp. are capable of colonizing and infecting the underground
      portions of living plants and causing economically important crop diseases such
      as potato common scab (CS). Research into the mechanisms of Streptomyces plant
      pathogenicity has led to the identification and characterization of several
      phytotoxic secondary metabolites that are known or suspected of contributing to
      diseases in various plants. The best characterized are the thaxtomin phytotoxins,
      which play a critical role in the development of CS, acid scab and soil rot of
      sweet potato. In addition, the best-characterized CS-causing pathogen,
      Streptomyces scabies, produces a molecule that is predicted to resemble the
      Pseudomonas syringae coronatine phytotoxin and which contributes to seedling
      disease symptom development. Other Streptomyces phytotoxic secondary metabolites
      that have been identified include concanamycins, FD-891 and borrelidin.
      Furthermore, there is evidence that additional, unknown metabolites may
      participate in Streptomyces plant pathogenicity. Such revelations have
      implications for the rational development of better management procedures for
      controlling CS and other Streptomyces plant diseases. 

PMID- 24131732
TI  - Pro-adrenomedullin, pro-endothelin-1, procalcitonin, C-reactive protein and
      mortality risk in critically ill children: a prospective study.
AB  - INTRODUCTION: We tested the hypothesis that higher mid-regional pro
      adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1),
      procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations would be
      associated with increased prediction of mortality risk scores. METHODS:
      Prospective observational study set in two pediatric intensive care units
      (PICUs). Two-hundred-thirty-eight patients were included. MR-proADM, CT-proET-1,
      PCT and CRP levels were compared between children with PRISM III and PIM 2 > p75
      (Group A; n = 33) and the rest (Group B; n = 205). RESULTS: Median (range) MR
      proADM levels were 1.39 nmol/L (0.52-12.67) in group A versus 0.54 (0.15-3.85) in
      group B (P < 0.001). CT-proET-1 levels were 172 pmol/L (27-500) versus 58 (4-447)
      (P < 0.001). PCT levels were 7.77 ng/mL (0.34-552.00) versus 0.28 (0.02-107.00)
      (P < 0.001). CRP levels were 6.23 mg/dL (0.08-28.25) versus 1.30 mg/dL (0.00
      42.09) (P = 0.210). The area under the ROC curve (AUC) for the differentiation of
      group A and B was 0.87 (95% CI:0.81-0.821) for MR-proADM, 0.86 (95% CI:0.79-0.92)
      for CT-proET-1 and 0.84 (95% CI:0.74-0.94) for PCT. A MR-proADM > 0.79 nmol/L had
      93% sensitivity and 76% specificity to differentiate groups, whereas a CT-proET-1
      > 123 pmol/L had 77% sensitivity and 84% specificity, and a PCT concentration >
      2.05 ng/mL had 80% sensitivity and specificity. CONCLUSIONS: In critically ill
      children, high levels of MR-proADM, CT-proET-1 and PCT were associated with
      increased prediction of mortality risk scores. MR-proADM, CT-proET-1 and PCT
      concentrations higher than 0.80 nmol/L, 123 pmol/L and 2 ng/mL, respectively,
      could be used by clinicians to identify critically ill children at higher
      prediction of risk death scores.

PMID- 24131733
TI  - An empirical comparison of knowledge and skill in the context of traditional
      ecological knowledge.
AB  - BACKGROUND: We test whether traditional ecological knowledge (TEK) about how to
      make an item predicts a person's skill at making it among the Tsimane' (Bolivia).
      The rationale for this research is that the failure to distinguish between
      knowledge and skill might account for some of the conflicting results about the
      relationships between TEK, human health, and economic development. METHODS: We
      test the association between a commonly-used measure of individual knowledge
      (cultural consensus analysis) about how to make an arrow or a bag and a measure
      of individual skill at making these items, using ordinary least-squares
      regression. The study consists of 43 participants from 3 villages. RESULTS: We
      find no association between our measures of knowledge and skill (core model, p >
      0.5, R2 = .132). CONCLUSIONS: While we cannot rule out the possibility of a real
      association between these phenomena, we interpret our findings as support for the
      claim that researchers should distinguish between methods to measure knowledge
      and skill when studying trends in TEK.

PMID- 24131735
TI  - Visualizing genomic information across chromosomes with PhenoGram.
AB  - BACKGROUND: With the abundance of information and analysis results being
      collected for genetic loci, user-friendly and flexible data visualization
      approaches can inform and improve the analysis and dissemination of these data. A
      chromosomal ideogram is an idealized graphic representation of chromosomes.
      Ideograms can be combined with overlaid points, lines, and/or shapes, to provide
      summary information from studies of various kinds, such as genome-wide
      association studies or phenome-wide association studies, coupled with genomic
      location information. To facilitate visualizing varied data in multiple ways
      using ideograms, we have developed a flexible software tool called PhenoGram
      which exists as a web-based tool and also a command-line program. RESULTS: With
      PhenoGram researchers can create chomosomal ideograms annotated with lines in
      color at specific base-pair locations, or colored base-pair to base-pair regions,
      with or without other annotation. PhenoGram allows for annotation of chromosomal
      locations and/or regions with shapes in different colors, gene identifiers, or
      other text. PhenoGram also allows for creation of plots showing expanded
      chromosomal locations, providing a way to show results for specific chromosomal
      regions in greater detail. We have now used PhenoGram to produce a variety of
      different plots, and provide these as examples herein. These plots include
      visualization of the genomic coverage of SNPs from a genotyping array,
      highlighting the chromosomal coverage of imputed SNPs, copy-number variation
      region coverage, as well as plots similar to the NHGRI GWA Catalog of genome-wide
      association results. CONCLUSIONS: PhenoGram is a versatile, user-friendly
      software tool fostering the exploration and sharing of genomic information.
      Through visualization of data, researchers can both explore and share complex
      results, facilitating a greater understanding of these data.

PMID- 24131736
TI  - Safety and pharmacokinetics of PF-04360365 following a single-dose intravenous
      infusion in Japanese subjects with mild-to-moderate Alzheimer's disease: a
      multicenter, randomized, double-blind, placebo-controlled, dose-escalation study.
AB  - OBJECTIVE: PF-04360365 is a humanized IgG(2)Deltaa anti-amyloid beta (Abeta)
      antibody designed to improve outcome in Alzheimer's disease (AD). Single doses of
      0.1 - 10 mg/kg were safe and well tolerated in Western (mostly Caucasian)
      subjects with mild-to-moderate AD. This Phase 1, multicenter, randomized, double
      blind, dose-escalation study was the first to evaluate the safety,
      pharmacokinetics, pharmacodynamics, and immunogenicity of PF-04360365 in Japanese
      subjects. MATERIALS AND METHODS: 30 subjects with mild-to-moderate AD were
      enrolled. In each cohort, 3 subjects received PF-04360365 (0.1, 0.5, 1, 5, or 10
      mg/kg) and 1 subject received placebo as a single 2-hour intravenous infusion.
      Subjects were monitored as inpatients for 24 hours and then as outpatients for 1
      year. RESULTS: All subjects completed the study. There were no serious or
      National Cancer Institute Common Terminology Criteria for Adverse Events grade >=
      3 adverse events, hypersensitivity reactions, or antidrug antibodies. No clinical
      or MRI evidence of brain microhemorrhage, cerebral edema, or encephalitis was
      observed. PF-04360365 plasma concentrations increased with dose, and
      pharmacokinetics were consistent with a small steady-state volume of
      distribution, slow clearance, and long elimination half-life. Cerebrospinal fluid
      (CSF):plasma ratios were < 0.5%. Plasma Abeta species showed dose-dependent
      increases in C(max) and AUC(infinity), but CSF biomarkers did not differ clearly
      between treatment arms. CONCLUSIONS: PF-04360365 was safe and well tolerated in
      Japanese subjects. Pharmacokinetics and plasma pharmacodynamic responses in
      Japanese subjects were comparable to those in Western subjects. *No longer
      affiliated with Pfizer.

PMID- 24131734
TI  - Acrolein exposure suppresses antigen-induced pulmonary inflammation.
AB  - BACKGROUND: Adverse health effects of tobacco smoke arise partly from its
      influence on innate and adaptive immune responses, leading to impaired innate
      immunity and host defense. The impact of smoking on allergic asthma remains
      unclear, with various reports demonstrating that cigarette smoke enhances asthma
      development but can also suppress allergic airway inflammation. Based on our
      previous findings that immunosuppressive effects of smoking may be largely
      attributed to one of its main reactive electrophiles, acrolein, we explored the
      impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic
      asthma. METHODS: C57BL/6 mice were sensitized to ovalbumin (OVA) by
      intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7,
      and challenged with aerosolized OVA on days 14-16. In some cases, mice were also
      exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14-17. Lung tissues or
      brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single
      initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last
      OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were
      measured in BALF, and lung tissue samples were collected for analysis of mucus
      and Th1/Th2 cytokine expression, determination of protein alkylation, cellular
      thiol status and transcription factor activity. RESULTS: Exposure to acrolein
      following OVA challenge of OVA-sensitized mice resulted in markedly attenuated
      allergic airway inflammation, demonstrated by decreased inflammatory cell
      infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly
      depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2
      pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and
      induction of Nrf2-target genes such as HO-1. Additionally, analysis of
      inflammatory signaling pathways showed suppressed activation of NF-kappaB and
      marginally reduced activation of JNK in acrolein-exposed lungs, associated with
      increased carbonylation of RelA and JNK. CONCLUSION: Acrolein inhalation
      suppresses Th2-driven allergic inflammation in sensitized animals, due to direct
      protein alkylation resulting in activation of Nrf2 and anti-inflammatory gene
      expression, and inhibition of NF-kappaB or JNK signaling. Our findings help
      explain the paradoxical anti-inflammatory effects of cigarette smoke exposure in
      allergic airways disease.

PMID- 24131737
TI  - Montelukast sodium-induced hematuria: a case report and literature review of 19
      cases in mainland China.
AB  - We report a rare case of montelukast sodium-induced hematuria in a 58-year-old
      female patient with allergic rhinitis. Renal function returned to normal after
      drug withdrawal. We reviewed 19 case reports of adverse reactions associated with
      montelukast sodium in mainland China and found that (1) 37% of patients were
      pediatric patients, (2) psychiatric disorders, rashes and uropoietic organs
      symptom were common, (3) uropoietic organ symptoms reported in mainland China
      were very rare abroad. The clinician in China should be vigilant about the
      adverse reaction of montelukast sodium and further studies are needed to explore
      the pathogenesis of montelukast-induced uropoietic organ symptoms. 

PMID- 24131738
TI  - Marked reductions in visual impairment due to diabetic retinopathy achieved by
      efficient screening and timely treatment.
AB  - PURPOSE: Diabetic retinopathy (DR) is the most common complication of diabetes
      and needs to be diagnosed early to prevent severe sight-threatening retinopathy.
      Digital photography with telemedicine connections is a novel way to deliver cost
      effective, accessible screening to remote areas. Screening for DR in a mobile eye
      examination unit (EyeMo) is compared to traditional service models (i.e. local
      municipal services or a commercial service provider). The quality of images,
      delays from screening to treatment, the stage of DR, coverage of screening and
      the rate of visual impairment due to DR are evaluated. METHODS: EyeMo utilizes
      telemedicine technology. The electronic databases of the hospital and information
      from the Finnish Register of Visual Impairment were used to determine delays and
      the rate of visual impairment. RESULTS: Fourteen thousand eight hundred and sixty
      six fundus photographs were taken in EyeMo in 2007-2011. Coverage reached 78% of
      potential clients. No DR was detected in 43%, mild background retinopathy in 23%,
      moderate or severe background retinopathy in 31% and proliferative retinopathy in
      3% of the evaluations. The quality of images was higher (p < 0.01) and delays
      shorter (p < 0.01) in EyeMo as compared to traditional service models. The rate
      of visual impairment due to DR decreased by 86% in the area covered by EyeMo, and
      the change compared favourably to the situation in the entire Finland (p <
      0.0005). CONCLUSION: EyeMo is a feasible model of telemedicine application for
      screening of DR. Effective screening and timely access to care may indeed have
      influenced the reduced rate of visual damage.

PMID- 24131739
TI  - Study of the association between the BMP4 gene and congenital anomalies of the
      kidney and urinary tract.
AB  - OBJECTIVE: To determine the frequency of different phenotypes for congenital
      anomalies of the kidney and urinary tract (CAKUT) in a Brazilian sample, and to
      evaluate the association between the CAKUT phenotypes and the BMP4 gene. METHODS:
      In this study, 457 Brazilian individuals were analyzed in an attempt to establish
      the association between the BMP4 gene and the CAKUT diagnosis. A case-control
      sample was genotyped for three BMP4 gene polymorphisms. RESULTS: Association data
      was established with CAKUT sample as a whole and with the three most important
      CAKUT phenotypes: multicystic dysplastic kidney disease (MDK), ureteropelvic
      junction obstruction (UPJO) and vesicoureteral reflux (VUR). When the sample was
      segregated in these three phenotypes, associations between the BMP4 gene were
      observed with UPJO and with MDK. Conversely, VUR was not associated to the
      polymorphisms of the BMP4 gene. CONCLUSIONS: The present data suggest that
      Brazilian individuals with polymorphisms of the BMP4 gene have a higher risk to
      develop CAKUT, especially the malformations related to nephrogenesis and initial
      branching such as MDK and UPJO. Conversely, VUR appeared not to be related to
      BMP4 gene.

PMID- 24131740
TI  - Eosinophilic colitis in infants.
AB  - OBJECTIVE: To review the literature for clinical data on infants with allergic or
      eosinophilic colitis. DATA SOURCE: MEDLINE search of all indexes was performed
      using the words "colitis or proctocolitis and eosinophilic" or "colitis or
      proctocolitis and allergic" between 1966 and February of 2013. All articles that
      described patients' characteristics were selected. DATA SYNTHESIS: A total of 770
      articles were identified, of which 32 met the inclusion criteria. The 32 articles
      included a total of 314 infants. According to the available information, 61.6% of
      infants were male and 78.6% were younger than 6 months. Of the 314 patients,
      49.0% were fed exclusively breast milk, 44.2% received cow's milk protein, and
      6.8% received soy protein. Diarrheal stools were described in 28.3% of patients.
      Eosinophilia was found in 43.8% (115/263) of infants. Colonic or rectal biopsy
      showed infiltration by eosinophils (between 5 and 25 per high-power field) in
      89.3% (236/264) of patients. Most patients showed improvement with the removal of
      the protein in cow's milk from their diet or the mother's diet. Allergy challenge
      tests with cow's milk protein were cited by 12 of the 32 articles (66 patients).
      CONCLUSIONS: Eosinophilic colitis occurs predominantly in the first six months of
      life and in males. Allergy to cow's milk was considered the main cause of
      eosinophilic colitis. Exclusion of cow's milk from the diet of the lactating
      mother or from the infant's diet is generally an effective therapeutic measure.

PMID- 24131741
TI  - First report on simplified diagnostic criteria for pre-hypertension and
      hypertension in a national sample of adolescents from the Middle East and North
      Africa: the CASPIAN-III study.
AB  - OBJECTIVE: This study aimed to simplify the diagnostic criteria of pre
      hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group, and to
      determine the accuracy of these simple indexes in a nationally-representative
      sample of Iranian children and adolescents. METHOD: The diagnostic accuracy of
      the indexes of systolic blood pressure-to-height ratio (SBPHR) and diastolic BPHR
      (DBPHR) to define pre-HTN and HTN was determined by the area under the curve of
      the receiver operator characteristic curves. RESULTS: The study population
      consisted of 5,738 Iranian students (2,875 females) with mean (SD) age of 14.7
      (2.4) years. The prevalences of pre-HTN and HTN were 6.9% and 5.6%. The optimal
      thresholds for defining pre-HTN were 0.73 in males and 0.71 in females for SBPHR,
      and 0.47 in males and 0.45 in females for DBPHR, respectively. The corresponding
      figures for HTN were 0.73, 0.71, 0.48, and 0.46, respectively. In both genders,
      the accuracies of SBPHR and DBPHR in diagnosing pre-HTN and HTN were
      approximately 80%. CONCLUSIONS: BPHR is a valid, simple, inexpensive, and
      accurate tool to diagnose pre-HTN and HTN in adolescents. The optimal thresholds
      of SBPHR and DBPHR were consistent with the corresponding figures in other
      populations of children and adolescents with different racial and ethnic
      backgrounds. Thus, it is suggested that the use of these indexes can be
      generalized in programs aiming to screen elevated blood pressure in the pediatric
      age group.

PMID- 24131742
TI  - Current evidence of percutaneous nucleoplasty for the cervical herniated disk: a
      systematic review.
AB  - BACKGROUND: Although percutaneous cervical nucleoplasty (PCN) has been shown to
      be both safe and effective, its application is still debated. PCN applied in disk
      herniation has not been systematically reviewed before, resulting in a limited
      insight into its effectiveness and safety, and the quality of available evidence.
      Therefore, we systematically reviewed the evidence on the efficacy and safety of
      PCN in patients with a (contained) herniated disk. METHODS: MEDLINE, EMBASE, and
      the Cochrane Library (Central Register of Controlled Trials) were searched for
      randomized controlled trials (RCTs) and nonrandomized studies using the following
      keywords: "Nucleoplasty," "Cervical," "Hernia," "Herniation," "Prolapse,"
      "Protrusion," "Intervertebral disk," and "Percutaneous disk decompression."
      First, all articles were appraised for methodological quality, and then, RCTs
      were graded for the level of evidence according a best-evidence synthesis,
      because a meta-analysis was not possible. Finally, the RCTs' applicability and
      clinical relevance also was assessed. RESULTS: Of 75 identified abstracts, 10
      full-text articles were included (3 RCTs and 7 nonrandomized studies). These
      studies represented a total of 1021 patients: 823 patients (>= 892 disks) were
      treated by PCN. All studies showed low methodological quality, except for two.
      The level of evidence of the RCTs was graded as moderate, with low to moderate
      applicability and clinical relevance. CONCLUSION: All included studies showed PCN
      to be an effective and safe procedure in the treatment of (contained) herniated
      disks at short-, mid-, and long-term follow-up. However, the level of evidence is
      moderate and shows only low to moderate applicability and clinical relevance.

PMID- 24131743
TI  - Factors associated with parent support for condom education and availability.
AB  - Expanding condom-related knowledge and skills and reducing barriers to condom use
      have the potential to help reduce pregnancies and sexually transmitted infections
      among youth. These goals are sometimes addressed through condom education and
      availability (CEA) programs as part of sexuality education in school. Parents are
      a key constituency in efforts to implement such programs. A representative
      statewide sample of households with children (N = 1,093) in California was
      employed to examine parent support for CEA and the potential influences of
      demographics (gender, age, and Hispanic ethnicity), sociodemographics (education,
      religious affiliation, religious service attendance, and political ideology), and
      condom-related beliefs (belief in condom effectiveness and belief that teens who
      use condoms during sex are being responsible) on parent support for CEA. The
      parents in our sample reported a high level of support for CEA (M = 3.23 on a 4
      point scale) and believing in a high level of condom effectiveness (M = 3.36 on a
      4-point scale). In addition, 84% of the parents agreed that teens who use condoms
      during sex are being responsible. Hierarchical regression analyses showed that
      parents who were younger, Hispanic, with a lower educational attainment, without
      a religious affiliation, less religiously observant, and politically liberal were
      more supportive of CEA. After controlling for these demographic and
      sociodemographic factors, condom effectiveness and responsibility beliefs each
      added independently to the predictability of parent support for CEA. These
      findings suggest that parent education related to condom effectiveness could help
      increase support for school-based CEA programs. 

PMID- 24131744
TI  - Hepatitis B virus reactivation and liver function after chemoembolization for
      hepatocellular carcinoma: How is it different from systemic chemotherapy?

PMID- 24131745
TI  - At the moment of occurrence of a fragility hip fracture, men have higher
      mechanical properties values in comparison with women.
AB  - BACKGROUND: It is well established that males have lower fracture risk in
      comparison with females, which suggests a higher bone resistance in men. The aim
      of our study was to find out if in older patients with hip fragility fractures,
      gender has also an impact on trabecular bone material behaviour, specifically to
      determine whether trabecular mechanical properties under compressive loading
      differ between men and women who suffered a fragility hip fracture. METHODS:
      Femoral epiphyses were consecutively collected during hip replacement surgery due
      to proximal femur fragility fracture. Trabecular bone cylinders were drilled and
      submitted to uniaxial compression tests and mechanical properties were assessed.
      RESULTS: Seventy-three patients, 55 women (mean age 81 years and standard
      deviation of 7 years) and 18 men (mean age 81 years and standard deviation of 8
      years) were evaluated. The ultimate stress of trabecular bone was significantly
      higher in men than in women: the median values and the interquartile range (IQR)
      were respectively 8.04(5.35-10.90) MPa vs. 4.46(3.02-7.73) MPa, (p-value =
      0.005). The same difference between male and female was observed in the Young's
      modulus: 293.68(166.67-538.18) MPa vs. 174.26(73.07-322.28) MPa, (p-value =
      0.028), and also in the energy to failure: 0.25(0.07-0.42) MJ/m3 vs. 0.11(0.05
      0.25) MJ/m3, (p-value = 0.058). These differences were also verified after
      adjusting the analysis for age in a multivariate model analysis. CONCLUSIONS: Our
      observations demonstrated that, even in a population who suffered a fragility hip
      fracture, men still have higher trabecular bone mechanical properties in
      comparison with women.

PMID- 24131746
TI  - Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic
      retinopathy: an updated meta-analysis.
AB  - BACKGROUND: The vascular endothelial growth factor (VEGFA) gene has been
      suggested to play an important role in the pathogenesis of diabetic retinopathy
      (DR). However, the results have been inconsistent. In this study, we performed a
      meta-analysis to clarify the associations between VEGFA polymorphisms and DR
      risk. METHODS: Published literature from PubMed, EMBASE, Web of Science and
      Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: A
      total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism
      and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were
      included in the meta-analysis. The results suggested that rs699947 polymorphism
      was marginally associated with DR under a homogeneous co-dominant model (AA vs.
      CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs.
      CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between
      rs2010963 polymorphism and DR was not significant under all genetic models (all p
      > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was
      only marginally significant among European populations under a dominant model (OR
      = 1.47, 95% CI = 1.07-2.02, p = 0.018), but not among East Asians. After
      exclusion of outliers which were the source of between-study heterogeneity, there
      was significant association between rs699947 polymorphism and DR under a
      homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even
      after multiple comparison correction. CONCLUSIONS: Our meta-analysis confirmed
      the significant association between rs699947 polymorphism and DR after exclusion
      of outliers, and rs2010963 polymorphism might be not associated with DR.

PMID- 24131747
TI  - Contralateral optic neuropathy and retinopathy associated with visual and
      afferent pupillomotor dysfunction following enucleation in six cats.
AB  - PURPOSE: To investigate contralateral optic neuropathy and retinopathy following
      enucleation in 6 cats. METHODS: Retrospective study. The medical records of cats
      with contralateral visual and afferent pupillomotor dysfunction following
      enucleation presented to the Animal Health Trust (AHT), Newmarket, UK, between
      January 1994 and January 2010 were reviewed. Information recorded included
      history, signalment, ophthalmic findings, electroretinography (ERG) (2/6) and MRI
      (3/6) findings and long-term outcome. Pearson's chi-square tests were used to
      compare breed proportions (P < 0.05). RESULTS: Six cats aged 1.5 to 11 (median
      5.5) years presented with mydriasis and/or visual deficits noted immediately
      following enucleation. Enucleation involved optic nerve (ON) ligation in all of
      the four cases for which this information was available. Ophthalmic findings
      included mydriasis with absent pupillary light reflex (PLR) (4/6), incomplete
      PLRs (2/6), absence of dazzle reflex (4/6) and absence of menace response (4/6).
      Funduscopy initially revealed multifocal peripapillary retinal lesions, with
      subsequent progressive optic nerve head (ONH) and retinal atrophy. ERG recordings
      revealed normal outer retinal function at 6 and 22 weeks (2/2). On MRI, the optic
      chiasm (OC) ipsilateral to the enucleation could not be identified and the
      contralateral OC was atrophied (3/3). CONCLUSIONS: The acute afferent ON deficits
      following enucleation, progressive ONH atrophy, normal outer retinal function and
      MRI demonstrating OC pathology are consistent with chiasmal injury due to
      traction on the ON during enucleation. Rostral traction on the globe to
      facilitate ON ligation is contraindicated in cats.

PMID- 24131748
TI  - Clinical Neuropathology practice guide 6-2013: morphology and an appropriate
      immunohistochemical screening panel aid in the identification of synovial sarcoma
      by neuropathologists.
AB  - AIMS: Pathologists are under increasing pressure to accurately subclassify
      sarcomas, yet neuropathologists have limited collective experience with rare
      sarcoma types such as synovial sarcoma. We reviewed 9 synovial sarcomas affecting
      peripheral nerve diagnosed by neuropathologists and explored the morphologic and
      immunohistochemical differences between these and MPNST. Our goal was to make
      practical recommendations for neuropathologists regarding which spindle cell
      tumors affecting nerve should be sent for SYT-SSX testing. METHODS: Clinical
      records and genetics were reviewed retrospectively and central pathology review
      of 9 synovial sarcomas and 6 MPNST included immunohistochemistry for SOX10, S100,
      BAF47, CK (lmw, pan, CK7, CK19), EMA, CD34, bcl2, CD99, and neurofilament.
      RESULTS: Common synovial sarcoma sites were brachial plexus, spinal and femoral
      nerve, none were "intra-neural", all had the SYTSSX1 translocation, and 6/9 were
      monophasic with myxoid stroma and distinct collagen. Half of the monophasic
      synovial sarcomas expressed CK7, CK19 or panCK in a "rare positive cells
      pattern", 8/9 (89%) expressed EMA, and all were SOX10 immunonegative with reduced
      but variable BAF47 expression. CONCLUSIONS: We recommend that upon encountering a
      cellular spindle cell tumor affecting nerve neuropathologists consider the
      following: 1) SYT-SSX testing should be performed on any case with morphology
      suspicious for monophasic synovial sarcoma including wiry or thick bands of
      collagen and relatively monomorphous nuclei; 2) neuropathologists should employ a
      screening immunohistochemical panel including one of CK7, panCK or CK19, plus
      EMA, S100 and SOX10, and 3) SYT-SSX testing should be performed on any spindle
      cell tumor with CK and/or EMA immunopositivity if SOX10 immunostaining is
      negative or only labels entrapped nerve elements.

PMID- 24131749
TI  - Olfactory dysfunction related to TDP-43 pathology in amyotrophic lateral
      sclerosis.
AB  - AIMS: To clarify a possible contribution of TDP-43 pathology to odor dysfunction
      in amyotrophic lateral sclerosis patients. CASE REPORT: An 83-year-old woman
      suffered from muscle weakness, which started to deteriorate during the previous
      half year. In addition to her pyramidal signs, lower motor involvement was shown
      by needle electromyography; this upper and lower motor neuron involvement was
      suggestive of probable ALS. She presented with severe odor impairments but
      relatively preserved cognitive functions. Her autopsy findings revealed TDP-43
      positive inclusions in the spinal motor neurons and cerebral limbic system
      without significant tau or alpha-synuclein deposits. DISCUSSION: This case showed
      evidence suggesting that olfactory dysfunction was probably related to limbic TDP
      43 pathology and was possibly independent of her Alzheimer pathology. Olfactory
      dysfunction does not necessarily indicate the presence of tau or alpha-synuclein
      pathology and could be an early sign of ALS with the limbic involvement of TDP-43
      pathology even when cognitive functions are preserved.

PMID- 24131750
TI  - Medulloblastoma with multi-lineage differentiation including myogenic and
      melanotic elements: a case report with molecular data.
AB  - We present an unusual medulloblastoma in a 3.9-year-old boy who had a 2-week
      history of nausea and vertigo. MRI revealed a 5*5.5*5 cm sized tumor located in
      the fourth ventricle and spinal leptomeningeal dissemination. The patient was
      treated according to the MET-HIT 2000-BIS4 protocol but showed tumor progression
      after 6 months and died 9 months postoperatively. Histopathologically and
      immunohistochemically, the tumor showed PNET-like areas with focal anaplasia,
      admixed rhabdomyoblastic and pigmented elements, cartilage and bone formation, as
      well as areas with neurocytic and glial differentiation. Neither CTNNB1 mutation
      nor MYCC/MYCN amplification was detected. The combination of rhabdomyoblastic and
      melanotic elements in medulloblastoma is exceptionally rare. Although the
      histopathological features suggested a teratoid tumor, the endodermal cell
      lineage required for this diagnosis was not present. An atypical teratoid
      rhabdoid tumor was ruled out due to the presence of the INI1-protein. Regarding
      the molecular profile with 1q and 17q chromosomal gains and loss of chromosome 8,
      this tumor could be compatible with a molecular medulloblastoma Group 3 or 4.
      Yet, it cannot be definitively ruled out that medulloblastomas with multi-lineage
      differentiation represent a distinct subgroup of medulloblastoma, and it remains
      to be clarified whether these tumors are associated with a distinct clinical
      behavior. 

PMID- 24131751
TI  - Renal cell carcinoma metastatic to meningioma: tumor-to-tumor metastasis.

PMID- 24131752
TI  - Panencephalopathic-type sporadic Creutzfeldt-Jakob disease with circumscribed
      spongy foci.

PMID- 24131753
TI  - An analysis of cervical non-infectious inflammatory myelitis risk factors.
AB  - BACKGROUND: Non-infectious inflammatory myelitis or non-infectious myelitis (NIM)
      is an inflammatory condition that occurs following an immune response in the
      central nervous system (CNS). In cases of spinal disc degeneration, multiple
      factors converge to cause pathologic changes in disc structure. To date, no
      studies have examined the potential relationship between disc degeneration and
      NIM. OBJECTIVES: To investigate the relationship between cervical NIM and
      cervical disc degeneration. METHODS: Magnetic resonance imaging (MRI) was used to
      examine 85 patients with cervical NIM. Peripheral levels of the pro-inflammatory
      cytokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were
      also measured. Non-infectious myelitis occurrence rates and TNF-alpha and IL-6
      levels were compared between patients with cervical disc degeneration and a
      control group. The relationship between cervical NIM and cervical disc
      degeneration was analyzed with logistic regression and a receiver operating
      characteristic (ROC) curve. RESULTS: Magnetic resonance imaging showed that 78.8%
      of patients with myelitis exhibited disc degeneration compared to only 18.9% of
      the control group. Moreover, IL-6 and TNF-alpha levels in patients with NIM were
      significantly higher than those in the control group; levels of these
      inflammatory cytokines were even higher in NIM patients with cervical disc
      degeneration than in those without. CONCLUSIONS: Our results suggest that
      patients with cervical NIM have a higher incidence of cervical disc degeneration,
      indicating that cervical disc degeneration is likely a possible risk factor in
      cervical NIM progression. Future quantitative studies are required to confirm
      this observation.

PMID- 24131754
TI  - A case of Mycobacterium mucogenicum infection in a liver transplant recipient and
      a review of the literature.
AB  - Bacterial, viral, and fungal infections can be devastating in a postoperative
      liver transplant recipient on multidrug immunosuppressive therapy. Various
      atypical (nontuberculous mycobacteria [NTM]) mycobacterial infections have been
      reported in the solid organ transplant population, but to our knowledge, no cases
      of Mycobacterium mucogenicum infections have been reported. Here, we report a
      case of a patient with end-stage liver disease secondary to primary biliary
      cirrhosis, model for end-stage liver disease score of 29, who underwent deceased
      donor orthotopic liver transplantation, with her postoperative course complicated
      by multiple pleural effusions and peritonitis. Despite numerous courses of
      antibiotics, her condition did not improve. Acid-fast bacilli cultures grew M.
      mucogenicum, which was then treated with appropriate antimicrobical therapy. M.
      mucogenicum, a rapidly growing NTM that can be present in water contamination,
      should be recognized as a potential source of infection, especially in the
      immunocompromised population. 

PMID- 24131755
TI  - Insulin glargine versus other types of basal insulin-clinical and tumor
      characteristics in patients with breast carcinoma.
AB  - BACKGROUND: Recent epidemiological studies have suggested that some insulin
      analogues could be associated with an increased risk of cancer. The aim of this
      retrospective study was to examine whether patients with diabetes mellitus (DM)
      using insulin glargine have a higher tumor stage of breast carcinoma in
      comparison to patients using other types of insulin. METHODS: We performed a
      chart review of 79 surgically treated breast carcinoma patients (mean age of 66.5
      years; range 38-86 years) who were on insulin. Insulin glargine was used in 13
      patients, while the other 66 patients were on other types of insulin. Clinical
      and histopathology characteristics of patients on glargine versus other types of
      insulin were compared using a chi-square test and non-parametric statistical
      analysis. RESULTS: DM type 1 and DM type 2 was present in 14 and 65 patients,
      respectively. The mean tumor size was 2.98 cm. The TNM tumor stage at diagnosis
      was not higher among patients on glargine compared to patients on other types of
      insulin (T1/T2 85% vs. 68%, T3/T4 15% vs. 32%, p = 0.32; N1 54% vs. 58%, p =
      0.80; M1 8% vs. 6%, respectively). No significant differences between both study
      groups (glargine vs. other types of insulin) were found in the ages of the
      patients, their BMI, tumor histology, grade, number of metastatic lymph nodes,
      hormone receptors or HER-2 status. CONCLUSION: We could not show that patients
      with DM using insulin glargine have a higher tumor stage of breast carcinoma in
      comparison to those using other types of insulin.

PMID- 24131756
TI  - Expression of epidermal growth factor receptor is an independent prognostic
      factor for esophageal squamous cell carcinoma.
AB  - BACKGROUND: The overall survival of patients with esophageal squamous cell
      carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based
      on histological assessment of tumor invasion and lymph node metastasis, but a
      biomarker with better predictive accuracy could be more useful. Because
      overexpression of epidermal growth factor receptor (EGFR) has been associated
      with poor prognosis, this study investigated whether EGFR is an independent
      prognostic factor for overall survival and disease-free survival of ESCC
      patients. METHODS: ESCC tissue specimens from 243 patients obtained during
      surgical resection between 1980 and 1997 were retrieved for immunohistochemical
      analysis of EGFR expression. RESULTS: The data showed that EGFR protein was
      overexpressed in 187 of 243 (77%) ESCC tissues. Elevated expression was
      associated with higher pathologic tumor stages (P = 0.001), lymph node metastasis
      (P = 0.002), and higher Union for International Cancer Control (UICC) stage (P
      <0.0001), as well as poorer disease-free survival and overall survival of ESCC
      patients (P <0.0001). A multivariate analysis showed that overexpression of EGFR
      protein was an independent factor for disease-free survival (P = 0.003) and
      overall survival (P = 0.001) of these patients. Subgroup analysis of patients
      with stage IIA (UICC 2002) showed that EGFR overexpression was associated with
      poorer disease-free survival (P = 0.007) and overall survival (P = 0.010) of the
      patients in univariate analyses. CONCLUSIONS: The current study demonstrated that
      EGFR overexpression was an independent prognostic factor for overall survival and
      disease-free survival of ESCC patients. However, targeting of EGFR activity using
      gefitinib or erlotinib could be useful for clinical treatment of ESCC patients.

PMID- 24131757
TI  - The association of body-mass index and depressed mood with knee pain and activity
      limitations in knee osteoarthritis: results from the Amsterdam osteoarthritis
      cohort.
AB  - BACKGROUND: Body-mass index (BMI) and depressed mood are both positively
      associated with pain and activity limitations in knee osteoarthritis (OA), and
      are interrelated. The aims of the present study were: 1) to assess whether BMI
      and depressed mood are independently associated with knee pain and activity
      limitations; and 2) to compare the relative contributions of BMI and depressed
      mood to knee pain and activity limitations. METHODS: A cross-sectional study in
      294 patients with clinical knee OA. Regression analyses were performed with knee
      pain or activity limitations (self-reported and performance-based) as dependent
      variables, and BMI and depressed mood as independent variables. All analyses were
      adjusted for age, gender, marital status, education level, radiographic OA and
      comorbidity. Dominance analyses were performed to examine the relative
      contributions of BMI and depressed mood to knee pain and activity limitations.
      RESULTS: BMI and depressed mood were positively and independently associated with
      knee pain and activity limitations. BMI and depressed mood explained small parts
      (3.0% and 2.3%, respectively) of variance in knee pain. BMI explained a
      substantial part of variance in both self-reported (9.8%) and performance-based
      (20.4%) activity limitations, while depressed mood explained a small part of
      variance (3.1% in self-reported and 2.6% in performance-based activity
      limitations). CONCLUSIONS: In patients with knee OA both BMI and depressed mood
      seem to be independently associated with knee pain and activity limitations. The
      contribution of BMI to activity limitations is most substantial, thereby offering
      a relevant target for interventions.

PMID- 24131758
TI  - The current status of ethnobiological research in Latin America: gaps and
      perspectives.
AB  - BACKGROUND: Recent reviews have demonstrated an increase in the number of papers
      on ethnobiology in Latin America. Among factors that have influenced this
      increase are the biological and cultural diversity of these countries and the
      general scientific situation in some countries. This study aims to assess the
      panorama of ethnobiological research in Latin America by analyzing its evolution,
      trends, and future prospects. METHODS: To conduct this study, we searched for
      papers in the Scopus (http://www.scopus.com) and Web of Science
      (http://www.isiknowledge.com) databases. The search was performed using
      combinations of keywords and the name of each Latin American country. The
      following countries were included in this study: Argentina, Bolivia, Brazil,
      Chile, Colombia, Costa Rica, Cuba, Ecuador, Guatemala, Haiti, Honduras, Mexico,
      Panama, Paraguay, Peru, Venezuela, and Uruguay. RESULTS AND CONCLUSIONS:
      According to our inclusion criteria, 679 ethnobiological studies conducted in
      Latin America were found for the period between 1963 and 2012. Of these studies,
      289 (41%) were conducted in Brazil, 153 in Mexico (22%), 61 in Peru (9%), 58 in
      Argentina (8%), 45 in Bolivia (6%), and 97 (14%) in other Latin American
      countries. The increased number of publications related to this area of knowledge
      in recent years demonstrates the remarkable growth of ethnobiology as a science.
      Ethnobiological research may be stimulated by an increase in the number of
      scientific events and journals for study dissemination and by the creation of
      undergraduate courses and graduate programs to train ethnoscientists who will
      produce high-quality studies, especially in certain countries.

PMID- 24131759
TI  - Corticosteroids injection in rotator cuff tears in elderly patient: pain outcome
      prediction.
AB  - AIM: The aim of this prospective study was to evaluate the effect of
      corticosteroids intra-articular injections on pain in patients with rotator cuff
      tear (RCT), and to identify predictors for pain outcomes. METHODS: A total of 60
      patients with RCT were enrolled. All patients underwent rehabilitation; 20
      patients received a single intra-articular injection of 40 mg triamcinolone
      acetonide and 20 patients had a repeat injection at a 21-day interval. Backward
      stepwise regression analysis was used to predict effectiveness and improvement of
      pain. The independent variables were age, sex, symptom duration, tear size,
      passive range of motion (ROM), active ROM, non-steroidal anti-inflammatory drugs
      request, pain at rest, number of triamcinolone injections and severity of
      osteoarthritis at admission. RESULTS: At 3 and 6 months, patients who received
      triamcinolone had higher effectiveness and improvement in pain during activities
      and pain at night than those of control group. At the 3-month interval post
      therapy, active ROM was the only predictor for effectiveness in pain during
      activity, effectiveness in pain at night and improvement in pain at night. Six
      months after therapy, active ROM was a predictor for improvement in pain at
      night. Age was a predictor for effectiveness in pain at night, whereas tear size
      of RCT was a predictor for effectiveness and improvement in pain during activity.
      CONCLUSIONS: Corticosteroids can relieve pain in RCT. Active ROM is the most
      important predictor of pain outcomes. This finding can be useful to physicians
      when deciding on the type of patients who might best benefit from intra-articular
      injections of corticosteroids.

PMID- 24131760
TI  - Awake bruxism in a patient with Alzheimer's dementia.

PMID- 24131761
TI  - Takotsubo cardiomyopathy in a senile female patient after transcatheter coil
      embolization of patent arterial duct.

PMID- 24131762
TI  - Incarcerated femoral hernia with presentation of abdominal pain without groin
      symptoms in an elderly man.

PMID- 24131763
TI  - Aggravation of Alzheimer's disease symptoms after the earthquake in Japan: A
      comparative analysis of subcategories.

PMID- 24131764
TI  - Addition of oral cavity brushing and rehabilitation reduces fever in tube-fed
      patients.

PMID- 24131765
TI  - Is segmental bioelectrical impedance analysis a valid tool to assess muscle mass
      in the elderly?

PMID- 24131766
TI  - Re: Post-stroke delirium in Hong Kong: 1-year outcomes.

PMID- 24131767
TI  - Potential role of physiotherapists in polymedication of the elderly.

PMID- 24131768
TI  - Translation, cross-cultural adaptation, and validity of the Korean version of the
      pain sensitivity questionnaire in chronic pain patients.
AB  - The purpose of this study was to translate pain sensitivity questionnaires (PSQ)
      into the Korean language, perform a cross-cultural adaption of the PSQ, and
      validate the Korean version of PSQ in patients with degenerative spinal disease.
      The PSQ was translated forward and backward, cross-culturally adapted by 2
      independent translators, and approved by an expert committee. The final Korean
      version of the PSQ was tested on 72 patients with degenerative spinal disease.
      Test-retest reliability was evaluated for 60 patients (83%) who completed the
      second assessment in an interval of 4 weeks. The mean PSQ-minor, PSQ-moderate,
      and PSQ-total (standard deviation [SD]) were 5.40 (2.02), 6.46 (1.98), and 5.93
      (1.93), respectively. The PSQ-total, PSQ-minor, and PSQ-moderate of the Korean
      version showed very good internal consistencies determined by the Cronbach's
      alpha of 0.926, 0.869, and 0.877, respectively. For convergent validity, the PSQ
      scores of the Korean version showed significant correlations with pain
      catastrophizing scale (PCS) (r = 0.377, P = 0.002; r = 0.365, P = 0.003; r =
      0.362, P = 0.003 for PSQ-total, PSQ-minor, and PSQ-moderate of the Korean
      version, respectively). For test-retest reliability, the intraclass correlation
      coefficients were 0.782 for PSQ-total, 0.752 for PSQ-minor, and 0.793 for PSQ
      moderate. In conclusion, the validated Korean version of PSQ is a transculturally
      equivalent, reliable, and valid tool to assess individual pain sensitivity. 

PMID- 24131769
TI  - Effective process or dangerous precipice: qualitative comparative embedded case
      study with young people with epilepsy and their parents during transition from
      children's to adult services.
AB  - BACKGROUND: Transition from children's to adult epilepsy services is known to be
      challenging. Some young people partially or completely disengage from contact
      with services, thereby risking their health and wellbeing. We conducted a mixed
      method systematic review that showed current epilepsy transition models enabling
      information exchange and developing self-care skills were not working well. We
      used synthesised evidence to develop a theoretical framework to inform this
      qualitative study. The aim was to address a critical research gap by exploring
      communication, information needs, and experiences of knowledge exchange in
      clinical settings by young people and their parents, during transition from
      children's to adult epilepsy services. METHOD: Qualitative comparative embedded
      Case study with 2 'transition' cases (epilepsy services) in two hospitals. Fifty
      eight participants: 30 young people (13-19 years) and 28 parents were interviewed
      in-depth (individual or focus group). Clinical documents/guidelines were
      collated. 'Framework' thematic analysis was used. The theoretical framework was
      tested using themes, pattern matching and replication logic. Theory-based
      evaluation methods were used to understand how and why different models of
      service delivery worked. RESULTS: A joint epilepsy clinic for young people 14-17
      years coordinated by children's and adult services was more likely to influence
      young people's behaviour by facilitating more positive engagement with adult
      healthcare professionals and retention of epilepsy-related self-care information.
      Critical success factors were continuity of care, on-going and consistent age
      appropriate and person centred communication and repeated information exchange.
      Three young people who experienced a single handover clinic disengaged from
      services. Psychosocial care was generally inadequate and healthcare professionals
      lacked awareness of memory impairment. Parents lacked knowledge, skills and
      support to enable their child to independently self-care. Translation of
      transition policies/guidelines into practice was weak. CONCLUSION: Findings make
      a significant contribution to understanding why young people disengage from
      epilepsy services, why some parents prevent independent self-care, and what
      constitutes good communication and transition from the perspective of young
      people and parents. The type of service configuration, delivery and organisation
      influenced the behaviours of young people at transition to adult services. The
      novel theoretical framework was substantially supported, underwent further post
      hoc development and can be used in future practice/intervention development and
      research.

PMID- 24131770
TI  - Effects of rocuronium bromide on globe position and respiratory function in
      isoflurane-anesthetized dogs: a comparison between three different dosages.
AB  - OBJECTIVE: To evaluate the effect on globe position and respiration of three
      dosages of intravenous rocuronium in isoflurane-anesthetized dogs. ANIMAL
      STUDIED: Thirty-two dogs anesthetized for ophthalmic procedures. PROCEDURES: The
      dogs were divided into four groups, each of eight animals (G1-G4). G1, G2, G3
      received 0.075, 0.05, 0.03 mg/kg of IV rocuronium, respectively; G4 received 0.9%
      NaCl IV; all the treatments were administered when an end-tidal isoflurane of 1.1
      1.2% was reached. Anesthesia was obtained with dexmedetomidine (2.5 mcg/kg IV),
      methadone (0.1 mg/kg IV), propofol (2 mg/kg IV), and isoflurane in oxygen.
      Neuromuscular function was assessed with acceleromyography by stimulation of the
      peroneal nerve using the train-of-four (ToF) and the ToF ratio (ToFR). Monitoring
      of cardiovascular and respiratory functions was performed. Changes in globe
      position were recorded. RESULTS: All three dosages of rocuronium produced
      centralization of the globe. Duration was 24.3 +/- 4.2, 23.4 +/- 3.6, and 8.7 +/-
      2.8 min, for G1, G2, and G3, respectively. The control group did not show globe
      centralization. No significant differences were found among the four groups in
      cardiovascular and respiratory parameters. Minute volume and ToFR were
      significantly lower in G1 compared with baseline values. CONCLUSIONS: All doses
      of rocuronium resulted in globe centralization. The higher dose provoked a
      transient respiratory depression and some degree of skeletal muscular blockade
      detectable with ToFR. No alterations in respiratory activity were present when
      0.05 mg/kg was used. The 0.03 mg/kg dosage could be useful for very short
      ophthalmic procedures.

PMID- 24131771
TI  - Optimization and validation of a reversed-phase high performance liquid
      chromatography method for the measurement of bovine liver methylmalonyl-coenzyme
      a mutase activity.
AB  - BACKGROUND: Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent
      enzyme that catalyses the interconversion of (2R)-methylmalonyl-CoA to succinyl
      CoA. In humans, a deficit in activity of MCM, due to an impairment of
      intracellular formation of adenosylcobalamin and methylcobalamin results in a
      wide spectrum of clinical manifestations ranging from moderate to fatal.
      Consequently, MCM is the subject of abundant literature. However, there is a lack
      of consensus on the reliable method to monitor its activity. This metabolic
      pathway is highly solicited in ruminants because it is essential for the
      utilization of propionate formed during ruminal fermentation. In lactating dairy
      cows, propionate is the major substrate for glucose formation. In present study,
      a reversed-phase high performance liquid chromatography (RP-HPLC) was optimized
      and validated to evaluate MCM activity in bovine liver. The major aim of the
      study was to describe the conditions to optimize reproducibility of the method
      and to determine stability of the enzyme and its product during storage and
      processing of samples. RESULTS: Specificity of the method was good, as there was
      no interfering peak from liver extract at the retention times corresponding to
      methylmalonyl-CoA or succinyl-CoA. Repeatability of the method was improved as
      compared to previous RP-HPLC published data. Using 66 MUg of protein, intra-assay
      coefficient of variation (CV) of specific activities, ranged from 0.90 to 8.05%
      and the CV inter-day was 7.40%. Storage and processing conditions (frozen
      homogenate of fresh tissue vs. fresh homogenate of tissue snapped in liquid
      nitrogen) did not alter the enzyme activity. The analyte was also stable in liver
      crude extract for three frozen/thawed cycles when stored at -20 degrees C and
      thawed to room temperature. CONCLUSIONS: The improved method provides a way for
      studying the effects of stages of lactation, diet composition, and physiology in
      cattle on MCM activity over long periods of time, such as a complete lactation
      period. Interestingly, this sensitive and accurate method could benefit the study
      of the cobalamin status in experimental studies and clinical cases.

PMID- 24131772
TI  - Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs
      discriminates tumor subtypes, while extracellular matrix metalloproteinase
      inducer indicates prognosis.
AB  - BACKGROUND: Matrix metalloproteinases can promote invasion and metastasis, which
      are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing
      the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an
      inhibitor of matrix metalloproteinases and the extracellular matrix
      metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine
      their expression, localization and possible antagonistic action in the
      pathogenesis and progression of renal cell tumors in a retrospective study.
      METHODS: Tumor and adjacent normal tissues of 395 nephrectomized patients were
      immunostained for RECK and EMMPRIN on a tissue microarray. RESULTS: RECK strongly
      decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon
      signed rank test, P<0.001), and it discriminated tumor entities showing the
      highest expression in oncocytomas. EMMPRIN, however, could be significantly
      correlated to pT stage and Fuhrman grading (Spearman's correlation coefficient
      rs=0.289 and rs=0.382, respectively). Higher expression of EMMPRIN was associated
      with decreased overall survival in Kaplan-Meier analysis (P<0.001), and the
      EMMPRIN level could independently predict survival for cases without metastasis
      and involvement of lymph nodes. Decreased RECK expression was confirmed by
      Western blotting in tissue of eight normal/tumor matches of patients after
      radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous.
      CONCLUSIONS: We propose RECK down regulation in renal cell carcinoma to be an
      early event that facilitates tumor formation and progression. EMMPRIN, however,
      as a prognostic tumor marker, increases only when aggressiveness is proceeding
      and could add an additional step to invasive properties of renal cell carcinoma.

PMID- 24131773
TI  - Perceptions of Dutch health care professionals regarding the Care Standard for
      diabetes.
AB  - BACKGROUND: The Netherlands can be regarded as unique in the use of the
      Netherlands Diabetes Federation (NDF) Care Standard (CS) for diabetes. The need
      to understand the barriers obstructing optimal health care, the dissemination and
      implementation of health care innovations into daily practice and the extent to
      which health care professionals actually adhere to guidelines has been emphasized
      repeatedly. Therefore, the aim of the present study was to suggest ways to
      optimize the implementation of the CS by examining the perceptions of Dutch
      health care professionals regarding the CS and the barriers to using it. METHODS:
      A cross-sectional questionnaire survey was conducted among health care
      professionals (N = 1547) in 2010. RESULTS: A total of 39.6% (N = 1323) of the
      participating health care professionals possessed the CS. Only 15.5% of the
      professionals who were to some extent familiar with the CS (N = 1100) described
      themselves as working in complete accordance with the CS. The majority (83.9%)
      thought the CS contributed greatly to ensuring the quality of care; the judgment
      on the feasibility of working in accordance with the CS was positive (mean = 3.9
      on a 5-point Likert scale). However, professionals tended to perceive the
      guidelines issued by the own professional association as the norm for high
      quality diabetes care, rather than the CS. The main barrier to using the CS was
      the lack of effective lifestyle interventions (or access to them) to provide care
      for people with diabetes or those at increased risk for the disorder.
      CONCLUSIONS: A limited percentage of health care professionals were found to
      posses the CS. It is questionable whether possession of the CS is a prerequisite
      for delivering high quality care. Overall, professionals were largely positive
      about the CS, although only a minority indicated they were working in complete
      accordance with it. Professionals and professional organizations should be
      further educated about the content of the CS and especially its added value with
      respect to the guidelines for their own professional group, in terms of the
      multidisciplinary approach to diabetes care. Furthermore, attention should be
      given to the most important perceived barriers, to facilitate adherence to the
      CS.

PMID- 24131774
TI  - Does lamellar surgery for keratoconus experience the popularity it deserves?
AB  - PURPOSE: To analyse developments in surgical treatment for keratoconus (KC) by
      assessing rates and types of corneal surgery from 2005 to 2010. METHODS: The
      Dutch Transplantation Foundation supplied data on all keratoplasty procedures for
      KC performed from 2005 to 2010 in the Netherlands. Registration was carried out
      by the eyebank at allocation and by the surgeon at the time of surgery. The type
      of surgery was categorized as either a penetrating or a lamellar procedure.
      RESULTS: Five hundred and seventy-five anonymized records were received, with
      excellent data completion (99%). Patients undergoing penetrating surgery had on
      average a lower visual acuity, higher k-readings and were slightly older compared
      with the lamellar group. A previous corneal hydrops was recorded for 19.1% of
      patients. Regular penetrating keratoplasty decreased in popularity from 79.7% in
      2005 to 43.7% in 2010, due to the increased rate of lamellar surgery (42.5% in
      2010) and 'mushroom' penetrating keratoplasty (13.8% in 2010). When hydrops cases
      were excluded, popularity became equal (47.6% penetrating versus 52.4% lamellar
      surgery, in 2010). CONCLUSION: Lamellar surgery is gaining in popularity,
      although regular penetrating keratoplasty is still the more commonly performed
      procedure. Only when hydrops cases are excluded do transplant rates become
      comparable.

PMID- 24131775
TI  - N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial
      fibrillation in the Multi-Ethnic Study of Atherosclerosis: the effects of age,
      sex and ethnicity.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a common source of medical costs,
      morbidity and mortality. NT pro-brain natriuretic peptide (BNP) is a remarkably
      strong predictor of AF in older whites; we aimed to assess if this biomarker was
      as predictive in other racial groups. DESIGN: We used covariate-adjusted Cox
      model regressions to estimate the HRs of developing AF as a function of NT
      proBNP, and tested for interactions of NT proBNP with age, gender and
      race/ethnicity. SETTING: The Multi-Ethnic Study of Atherosclerosis (MESA).
      PATIENTS: 5518 subjects were followed over a median of 7.6 years. During this
      time, 267 developed AF. RESULTS: NT proBNP was statistically significantly
      associated with incident AF; for ln NT proBNP, the adjusted HR was 2.2 (95% CI
      1.9 to 2.5). Assessed by quintiles, the relationship between NT proBNP was strong
      and graded; the unadjusted HR for the highest quintile of NT proBNP was 23.7 (95%
      CI 11.1 to 50.6) and adjusted was 11.4 (95% CI 5.1 to 25.3). NT proBNP was an
      excellent predictor of incident AF in the younger and older age groups, in men
      and women and in the different race/ethnicity groups: the HR for ln NT proBNP as
      a predictor of incident AF ranged from 2.0 to 3.9 in each subgroup. CONCLUSIONS:
      NT proBNP is a robust predictor of incident AF; its prognostic value is more
      significant in younger patients and women compared with older patients and men.
      NT proBNP was also as strongly predictive in black patients, Hispanics and
      Asian/Chinese as in white patients despite a lower incidence of arrhythmia.

PMID- 24131776
TI  - Bats and birds increase crop yield in tropical agroforestry landscapes.
AB  - Human welfare is significantly linked to ecosystem services such as the
      suppression of pest insects by birds and bats. However, effects of biocontrol
      services on tropical cash crop yield are still largely unknown. For the first
      time, we manipulated the access of birds and bats in an exclosure experiment
      (day, night and full exclosures compared to open controls in Indonesian cacao
      agroforestry) and quantified the arthropod communities, the fruit development and
      the final yield over a long time period (15 months). We found that bat and bird
      exclusion increased insect herbivore abundance, despite the concurrent release of
      mesopredators such as ants and spiders, and negatively affected fruit
      development, with final crop yield decreasing by 31% across local (shade cover)
      and landscape (distance to primary forest) gradients. Our results highlight the
      tremendous economic impact of common insectivorous birds and bats, which need to
      become an essential part of sustainable landscape management. 

PMID- 24131777
TI  - Dynamical modelling of phenotypes in a genome-wide RNAi live-cell imaging assay.
AB  - BACKGROUND: The combination of time-lapse imaging of live cells with high
      throughput perturbation assays is a powerful tool for genetics and cell biology.
      The Mitocheck project employed this technique to associate thousands of genes
      with transient biological phenotypes in cell division, cell death and migration.
      The original analysis of these data proceeded by assigning nuclear morphologies
      to cells at each time-point using automated image classification, followed by
      description of population frequencies and temporal distribution of cellular
      states through event-order maps. One of the choices made by that analysis was not
      to rely on temporal tracking of the individual cells, due to the relatively low
      image sampling frequency, and to focus on effects that could be discerned from
      population-level behaviour. RESULTS: Here, we present a variation of this
      approach that employs explicit modelling by dynamic differential equations of the
      cellular state populations. Model fitting to the time course data allowed
      reliable estimation of the penetrance and time of appearance of four types of
      disruption of the cell cycle: quiescence, mitotic arrest, polynucleation and cell
      death. Model parameters yielded estimates of the duration of the interphase and
      mitosis phases. We identified 2190 siRNAs that induced a disruption of the cell
      cycle at reproducible times, or increased the durations of the interphase or
      mitosis phases. CONCLUSIONS: We quantified the dynamic effects of the siRNAs and
      compiled them as a resource that can be used to characterize the role of their
      target genes in cell death, mitosis and cell cycle regulation. The described
      population-based modelling method might be applicable to other large-scale cell
      based assays with temporal readout when only population-level measures are
      available.

PMID- 24131778
TI  - Effect of four additional physical education lessons on body composition in
      children aged 8-13 years--a prospective study during two school years.
AB  - BACKGROUND: Strategies for combating increasing childhood obesity is called for.
      School settings have been pointed out as potentially effective settings for
      prevention. The objective of this paper was to evaluate the effect of four
      additional Physical Education (PE) lessons/week in primary schools on body
      composition and weight status in children aged 8-13. METHODS: Children attending
      2nd to 4th grade (n = 632) in 10 public schools, 6 intervention and 4 control
      schools, participated in this longitudinal study during 2 school years. OUTCOME
      MEASURES: Primary: Body Mass Index (BMI) and Total Body Fat percentage (TBF%)
      derived from Dual Energy X ray Absorptiometry (DXA). Secondary: the moderating
      effect of overweight/obesity (OW/OB) and adiposity based on TBF% cut offs for
      gender. RESULTS: Intervention effect on BMI and TBF% (BMI: beta -0.14, 95% CI: 
      0.33; 0.04, TBF%: beta -0.08, 95% CI:-0.65;0.49) was shown insignificant.
      However, we found significant beneficial intervention effect on prevalence of
      OW/OB based on BMI (OR 0.29, 95% CI: 0.11;0.72). The intervention effect on
      adiposity based on TBF% cut offs was borderline significant (OR 0.64, 95% CI:0.
      39; 1.05). CONCLUSION: Four additional PE lessons/week at school can
      significantly improve the prevalence of OW/OB in primary schoolchildren. Mean BMI
      and TBF% improved in intervention schools, but the difference with controls was
      not significant. The intervention had a larger effect in children who were OW/OB
      or adipose at baseline.

PMID- 24131779
TI  - A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin
      dependent kinase inhibitor, administered weekly in subjects with advanced
      malignancies.
AB  - BACKGROUND: Dinaciclib, a small-molecule, cyclin-dependent kinase inhibitor,
      inhibits cell cycle progression and proliferation in various tumor cell lines in
      vitro. We conducted an open-label, dose-escalation study to determine the safety,
      tolerability, and bioactivity of dinaciclib in adults with advanced malignancies.
      METHODS: Dinaciclib was administered starting at a dose of 0.33 mg/m2, as a 2
      hour intravenous infusion once weekly for 3 weeks (on days 1, 8, and 15 of a 28
      day cycle), to determine the maximum administered dose (MAD), dose-limiting
      toxicities (DLTs), recommended phase 2 dose (RP2D), and safety and tolerability.
      Pharmacodynamics of dinaciclib were assessed using an ex vivo phytohemagglutinin
      lymphocyte stimulation assay and immunohistochemistry staining for retinoblastoma
      protein phosphorylation in skin biopsies. Evidence of antitumor activity was
      assessed by sequential computed tomography imaging after every 2 treatment
      cycles. RESULTS: Forty-eight subjects with solid tumors were treated. The MAD was
      found to be 14 mg/m2 and the RP2D was determined to be 12 mg/m2; DLTs at the MAD
      included orthostatic hypotension and elevated uric acid. Forty-seven (98%)
      subjects reported adverse events (AEs) across all dose levels; the most common
      AEs were nausea, anemia, decreased appetite, and fatigue. Dinaciclib administered
      at the RP2D significantly inhibited lymphocyte proliferation, demonstrating a
      pharmacodynamic effect. Ten subjects treated at a variety of doses achieved
      prolonged stable disease for at least 4 treatment cycles. CONCLUSIONS: Dinaciclib
      administered every week for 3 weeks (on days 1, 8, and 15 of a 28-day cycle) was
      generally safe and well tolerated. Initial bioactivity and observed disease
      stabilization support further evaluation of dinaciclib as a treatment option for
      patients with advanced solid malignancies. TRIAL REGISTRATION: ClinicalTrials.gov
      # NCT00871663.

PMID- 24131784
TI  - Functional magnetic resonance imaging of the ascending stages of the auditory
      system in dogs.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) is a technique able to
      localize neural activity in the brain by detecting associated changes in blood
      flow. It is an essential tool for studying human functional neuroanatomy
      including the auditory system. There are only a few studies, however, using fMRI
      to study canine brain functions. In the current study ten anesthetized dogs were
      scanned during auditory stimulation. Two functional sequences, each in
      combination with a suitable stimulation paradigm, were used in each subject.
      Sequence 1 provided periods of silence during which acoustic stimuli could be
      presented unmasked by scanner noise (sparse temporal sampling) whereas in
      sequence 2 the scanner noise was present throughout the entire session
      (continuous imaging). The results obtained with the two different functional
      sequences were compared. RESULTS: This study shows that with the proper
      experimental setup it is possible to detect neural activity in the auditory
      system of dogs. In contrast to human fMRI studies the strongest activity was
      found in the subcortical parts of the auditory pathways. Especially sequence 1
      showed a high reliability in detecting activated voxels in brain regions
      associated with the auditory system. CONCLUSION: These results indicate that fMRI
      is applicable for studying the canine auditory system and could become an
      additional method for the clinical evaluation of the auditory function of dogs.
      Additionally, fMRI is an interesting technique for future studies concerned with
      canine functional neuroanatomy.

PMID- 24131785
TI  - Historical perspectives of The American Association for Thoracic Surgery: Craig
      R. Smith.

PMID- 24131786
TI  - Tumor invasiveness as defined by the newly proposed IASLC/ATS/ERS classification
      has prognostic significance for pathologic stage IA lung adenocarcinoma and can
      be predicted by radiologic parameters.
AB  - OBJECTIVES: The International Association for the Study of Lung Cancer, American
      Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) have
      collaborated to propose a new pathologic classification of lung adenocarcinoma.
      In this classification, noninvasiveness and invasiveness have been newly defined
      for lung adenocarcinoma. The aims of this study were to validate the prognostic
      significance of tumor invasiveness as defined by the new IASLC/ATS/ERS
      classification and to assess the relationship between pathologic invasiveness and
      radiologic findings in pathologic stage IA lung adenocarcinoma. METHODS: We
      retrospectively reviewed 123 consecutive patients with pathologic stage IA lung
      adenocarcinoma. Pathologic data were classified according to the new
      IASLC/ATS/ERS classification. The following radiologic parameters were assessed
      using thin-section computed tomography: the ground-glass opacity ratio, tumor
      disappearance rate, and consolidation diameter. RESULTS: There were 54
      noninvasive and 69 invasive adenocarcinomas. Five-year overall survival rates for
      noninvasive adenocarcinoma and invasive adenocarcinoma were 100% and 78.4%,
      respectively; this difference was statistically significant (P < .01), indicating
      the prognostic value of this classification. Receiver operating characteristic
      curves of the ground-glass opacity ratio, tumor disappearance rate, and
      consolidation diameter identified the optimal cut-off values for predicting the
      presence of invasive tumors as 50%, 75%, and 10 mm, respectively. CONCLUSIONS: We
      found that by using the new IASLC/ATS/ERS classification, histologic subtypes of
      pathologic stage IA lung adenocarcinoma with prognostic value could be
      identified. Tumor invasiveness of lung adenocarcinoma as defined by this
      classification can be predicted by evaluating the ground-glass opacity ratio,
      tumor disappearance rate, and consolidation diameter on thin-section computed
      tomography.

PMID- 24131787
TI  - Impact of cardiac support device combined with slow-release prostacyclin agonist
      in a canine ischemic cardiomyopathy model.
AB  - BACKGROUND: The cardiac support device supports the heart and mechanically
      reduces left ventricular (LV) diastolic wall stress. Although it has been shown
      to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is
      limited by its lack of biological effects. In contrast, the slow-release
      synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling
      through biological mechanisms such as angiogenesis and attenuation of fibrosis.
      We therefore hypothesized that ONO-1301 plus a cardiac support device might be
      beneficial for the treatment of ischemic cardiomyopathy. METHODS: Twenty-four
      dogs with induced anterior wall infarction were assigned randomly to 1 of 4
      groups at 1 week postinfarction as follows: cardiac support device alone, cardiac
      support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.
      RESULTS: At 8 weeks post-infarction, LV wall stress was reduced significantly in
      the hybrid therapy group compared with the other groups. Myocardial blood flow,
      measured by positron emission tomography, and vascular density were significantly
      higher in the hybrid therapy group compared with the cardiac support device alone
      and sham groups. The hybrid therapy group also showed the least interstitial
      fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed
      by multidetector computed tomography and cardiac catheterization, and the lowest
      plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). CONCLUSIONS:
      The combination of a cardiac support device and the prostacyclin agonist ONO-1301
      elicited a greater reversal of LV remodeling than either treatment alone,
      suggesting the potential of this hybrid therapy for the clinical treatment of
      ischemia-induced heart failure.

PMID- 24131788
TI  - The high-affinity maltose switch MBP317-347 has low affinity for glucose:
      implications for targeting tumors with metabolically directed enzyme prodrug
      therapy.
AB  - Development of agents with high affinity and specificity for tumor-specific
      markers is an important goal of molecular-targeted therapy. Here, we propose a
      shift in paradigm using a strategy that relies on low affinity for fundamental
      metabolites found in different concentrations in cancerous and non-cancerous
      tissues: glucose and lactate. A molecular switch, MBP317-347, originally designed
      to be a high-affinity switch for maltose and maltose-like polysaccharides, was
      demonstrated to be a low-affinity switch for glucose, that is, able to be
      activated by high concentrations (tens of millimolar) of glucose. We propose that
      such a low-affinity glucose switch could be used as a proof of concept for a new
      prodrug therapy strategy denominated metabolically directed enzyme prodrug
      therapy (MDEPT) where glucose or, preferably, lactate serves as the activator.
      Accordingly, considering the typical differential concentrations of lactate found
      in tumors and in healthy tissues, a low-affinity lactate-binding switch analogous
      to the low-affinity glucose-binding switch MBP317-347 would be an order of
      magnitude more active in tumors than in normal tissues and therefore can work as
      a differential activator of anticancer drugs in tumors. 

PMID- 24131789
TI  - Increased mortality in systemic inflammatory response syndrome patients with high
      levels of coagulation factor VIIa.
AB  - BACKGROUND: The tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal
      role in inflammatory and coagulation responses in patients with systemic
      inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and
      FVIIa compete for binding to TF, their plasma levels determine if a catalytically
      active TF-FVIIa complex will be formed. OBJECTIVE: To study mortality in SIRS
      patients as a function of FVIIa and FVII levels in plasma. METHODS: This was a
      cohort study of 275 patients presenting with SIRS, aged 18 years or older and
      with an anticipated Intensive Care Unit (ICU) stay of at least 24 h. FVIIa was
      measured using a novel, quantitative assay that recognizes FVIIa, but not FVII.
      All-cause hospital mortality was followed over a period of 60 days. RESULTS: The
      percentage of FVII measured as FVIIa was higher in non-survivors than survivors
      (2.8%, IQR = 1-5.5% vs. 1.5%, IQR = 0.6-3.3%; P = 0.034). High levels of FVIIa
      were associated with decreased 60-day cumulative survival (62% vs. 81%, P =
      0.030); the opposite was observed for FVII (84% vs. 76%, P = 0.039). Patients
      with high-FVIIa and low-FVII levels had a three-fold increased hazard ratio (HR)
      compared with the patients that had low-FVIIa and high-FVII levels (HR = 3.24,
      95% confidence interval [CI] = 1.41-7.36). This association persisted after
      adjusting for the APACHE IV score (adjusted HR = 2.75, 95% CI = 1.2-6.27).
      CONCLUSIONS: SIRS patients with high-FVIIa and low-FVII on admission have an
      increased mortality risk, an association that is independent from the parameters
      included in the APACHE IV score.

PMID- 24131790
TI  - Sacral nerve stimulation lead implantation using the O-arm.
AB  - BACKGROUND: Sacral neuromodulation operations have usually been performed based
      on 2D fluoro images. However, sacral nerve stimulation lead implantation may be
      challenging when the normal anatomy is confused by obesity or congenital
      anomalies. Thus the surgical navigation and intraoperative imaging methods could
      be helpful as those same methods have proven to be feasible methods for guiding
      other surgical operations. Our recent knowledge about the O-arm in trauma pelvic
      operations encouraged us to evaluate the usefulness of O-arm guided navigation in
      sacral neuromodulation. Similar navigation would be useful for complex sacral
      nerve stimulation lead implantations. METHODS: In this preliminary article we
      report our experience of utilizing the orthopedically optimized O-arm to implant
      the S3 stimulation electrode in a patient. The 3D O-arm imaging was performed
      intraoperatively under surgical navigation control. General anesthesia was used.
      The obtained 3D image dataset was registered automatically into the patient's
      anatomy. The stimulation needle was guided and the tined lead electrode was
      implanted using navigation. RESULTS: The bony sacral structures were clearly
      visualized. Due to automatic registration, the navigation was practicable
      instantly after the O-arm scanning and operation could be performed successfully
      under navigation control. CONCLUSIONS: To our knowledge, this is the first
      published tined lead implantation which was guided based on the surgical
      navigation and intraoperative O-arm images. In this case, the applied method was
      useful and helped the surgeon to demarcate the region of surgical interest. The
      method is slightly more invasive than the formal technique but could be an option
      in anatomically challenging cases and reoperations. However, further evaluation
      with larger patient series is required before definitive recommendations can be
      made.

PMID- 24131791
TI  - Identification of a negative feedback loop between cyclic di-GMP-induced levels
      of IFI16 and p202 cytosolic DNA sensors and STING.
AB  - A host type I IFN response is induced by cytosolic sensing of the bacterial
      second messenger cyclic-di-GMP (c-di-GMP) by STING (stimulator of IFN genes).
      Because the STING, an adaptor protein, links the cytosolic detection of DNA by
      the cytosolic DNA sensors such as the IFN-inducible human IFI16 and murine p202
      proteins to the TBK1/IRF3 axis, we investigated whether c-di-GMP-induced
      signaling could regulate expression of IFI16 and p202 proteins. Here, we report
      that activation of c-di-GMP-induced signaling in human and murine cells increased
      steady-state levels of IFI16 and p202 proteins. The increase was c-di-GMP
      concentration- and time-dependent. Unexpectedly, treatment of cells with type I
      IFN decreased levels of the adaptor protein STING. Therefore, we investigated
      whether the IFI16 or p202 protein could regulate the expression of STING and
      activation of the TBK1/IRF3 axis. We found that constitutive knockdown of IFI16
      or p202 expression in cells increased steady-state levels of STING. Additionally,
      the knockdown of IFI16 resulted in activation of the TBK1/IRF3 axis. Accordingly,
      increased levels of the IFI16 or p202 protein in cells decreased STING levels.
      Together, our observations identify a novel negative feedback loop between c-di
      GMP-induced levels of IFI16 and p202 cytosolic DNA sensors and the adaptor
      protein STING. 

PMID- 24131792
TI  - Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20
      and VEGF production by human monocytes and macrophages.
AB  - Peripheral blood monocytes are recruited to inflammatory and tumor lesions where
      they undergo terminal differentiation into macrophages. Monocytes/macrophages
      integrate stimulatory and inhibitory signals present in the pathologic
      microenvironment through a defined repertoire of cell surface receptors, and
      deregulated expression of these molecules may result in amplification of
      inflammation or establishment of immune escape mechanisms. Characterization of
      the expression and function of these receptors is required for a better
      understanding of the regulation of monocyte/macrophage activity at pathologic
      sites. Hypoxia is a common feature of many pathological situations and an
      important regulator of monocyte/macrophage pro-inflammatory responses. In this
      study, we identify the leukocyte membrane antigen, CD300a, a member of the CD300
      superfamily of immunoregulatory receptors, as a new hypoxia-inducible gene in
      primary human monocytes and monocyte-derived macrophages. CD300a mRNA up
      regulation by hypoxia was rapid and reversible, paralleled by increased surface
      protein expression, and mediated by hypoxia-inducible factor-1alpha. CD300a
      induction was also triggered by the hypoxia-mimetic agent, desferrioxamine.
      CD300a exhibited both activating and inhibitory potential, differentially
      regulating CCL20 and vascular endothelial growth factor pro-inflammatory cytokine
      production by monocytes/macrophages upon triggering by an agonist Ab. These
      results suggest that CD300a induction by the hypoxic environment represents a
      mechanism of regulation of monocyte/macrophage pro-inflammatory responses at
      pathologic sites. 

PMID- 24131793
TI  - Sex differences in the generalization of fear as a function of retention
      intervals.
AB  - In previous studies using male rodents, context change disrupted a fear response
      at a short, but not a long, retention interval. Here, we examined the effects of
      context changes on fear responses as a function of time in male and female rats.
      Males displayed context discrimination at all intervals, whereas females
      exhibited generalization by 5 d. Ovariectomized females with no hormone
      replacement displayed context discrimination at 5 d, whereas those receiving
      17beta-estradiol generalized their fear response to a neutral context. These
      results demonstrate that fear generalization for contextual cues occurs faster in
      female rats and is mediated, in part, by estrogens. 

PMID- 24131795
TI  - Long-term exercise is needed to enhance synaptic plasticity in the hippocampus.
AB  - Exercise can have many benefits for the body, but it also benefits the brain by
      increasing neurogenesis, synaptic plasticity, and performance on learning and
      memory tasks. The period of exercise needed to realize the structural and
      functional benefits for the brain have not been well delineated, and previous
      studies have used periods of exercise exposure that range from as little as 3 d
      to up to 6 mo. In this study, we systematically evaluated the effects of
      differential running periods (3, 7, 14, 28, and 56 d) on both structural (cell
      proliferation and maturation) and functional (in vivo LTP) changes in the dentate
      gyrus of adult male Sprague-Dawley rats. We found that voluntary access to a
      running wheel for both short- and long-term periods can increase cell
      proliferation in the adult DG; however, increases in neurogenesis required longer
      term exposure to exercise. Increases in immature neurons were not observed until
      animals had been running for a minimum of 14 d. Similarly, short-term periods of
      wheel running did not facilitate LTP in the DG of adult animals, and reliable
      increases in LTP were only observed with 56 d of running. These results provide
      us with a greater understanding of the time course of wheel running access needed
      to enhance DG function. Furthermore, the results indicate that the new neurons
      produced in response to exercise in rats do not contribute significantly to
      synaptic plasticity until they mature. 

PMID- 24131794
TI  - Neuronal correlates of fear conditioning in the bed nucleus of the stria
      terminalis.
AB  - Lesion and inactivation studies indicate that the central amygdala (CeA)
      participates in the expression of cued and contextual fear, whereas the bed
      nucleus of the stria terminalis (BNST) is only involved in the latter. The basis
      for this functional dissociation is unclear because CeA and BNST form similar
      connections with the amygdala and brainstem fear effectors. To address this
      question, we recorded neurons in the anterolateral (AL) and anteromedial (AM)
      regions of BNST in rats subjected to auditory fear conditioning. During
      habituation, few neurons were responsive to the conditioned stimulus (CS). After
      fear conditioning, 20% of BNST-AL neurons developed inhibitory responses to the
      CS. In BNST-AM, 26% of neurons developed positive CS responses. The behavior of
      BNST-AM and -AL neurons during contextual fear paralleled their CS
      responsiveness: More BNST-AM neurons fired at higher rates during contextual
      freezing than movement, whereas the opposite was seen in BNST-AL cells. These
      findings point to regional differences in the activity of BNST-AL and -AM in
      relation to learned fear, raising the possibility that they exert opposite
      influences on fear output networks. However, given the similar behavior of BNST
      AM and -AL neurons in relation to cued and contextual fear, it remains unclear
      why lesion and inactivation of BNST differentially affect these two types of
      fear. Either neurons in a different BNST sector, not explored here, show a
      different activity profile in relation to the two forms of fear or
      inactivation/lesion studies inadvertently affected a structure adjacent to BNST,
      which is involved in contextual fear. 

PMID- 24131796
TI  - Characteristics of residency training associated with first-time pass rate on the
      American College of Veterinary Ophthalmologists certifying examination.
AB  - OBJECTIVE: The aim of this study was to examine the association of various
      aspects of veterinary ophthalmology residency training with the first-time pass
      rate (FTPR) of the American College of Veterinary Ophthalmologists (ACVO)
      examination, as well as the individual written, image recognition, animal
      examination, and surgical sections of the examination. PROCEDURES: Program type,
      resident evaluations, cumulative surgery and case logs, and scores from ACVO
      examinations from 2007 to 2010 were evaluated. RESULTS: Data were available for
      71 candidates. The overall FTPR was 35% (n = 25). For the different sections of
      the examination, FTPRs were as follows: written (68%), image recognition (76%),
      intraocular surgery (80%), extraocular surgery (65%), and animal examination
      (75%). The overall FTPR among candidates from academic residency (AR) programs
      was 43% (20 of 47), while the FTPR of residents in private practice (PPR)
      programs was 21% (5 of 24; P = 0.07). The AR candidates were more likely to pass
      the written portion than PPR residents (P = 0.02), and AR candidates had
      significantly more time off clinics (median 25%) vs PPR residents (median 18%; P
      = 0.007). The AR residents also had a higher reported percentage of direct
      supervision than PPR residents (95% vs 76%, respectively). Although PPR residents
      did significantly more surgeries and examined significantly more dogs and cats,
      those from ARs examined significantly more equine, bovine, avian, camelid, and
      reptile species. CONCLUSIONS: Overall, AR residents had a higher FTPR and were
      more likely to pass the written portion of the examination. Total case and
      surgery numbers were not associated with FTPR.

PMID- 24131797
TI  - High variance in reproductive success generates a false signature of a genetic
      bottleneck in populations of constant size: a simulation study.
AB  - BACKGROUND: Demographic bottlenecks can severely reduce the genetic variation of
      a population or a species. Establishing whether low genetic variation is caused
      by a bottleneck or a constantly low effective number of individuals is important
      to understand a species' ecology and evolution, and it has implications for
      conservation management. Recent studies have evaluated the power of several
      statistical methods developed to identify bottlenecks. However, the false
      positive rate, i.e. the rate with which a bottleneck signal is misidentified in
      demographically stable populations, has received little attention. We analyse
      this type of error (type I) in forward computer simulations of stable populations
      having greater than Poisson variance in reproductive success (i.e., variance in
      family sizes). The assumption of Poisson variance underlies bottleneck tests, yet
      it is commonly violated in species with high fecundity. RESULTS: With large
      variance in reproductive success (Vk >= 40, corresponding to a ratio between
      effective and census size smaller than 0.1), tests based on allele frequencies,
      allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio,
      and Tajima's D test) tend to show erroneous signals of a bottleneck. Similarly,
      strong evidence of population decline is erroneously detected when ancestral and
      current population sizes are estimated with the model based method MSVAR.
      CONCLUSIONS: Our results suggest caution when interpreting the results of
      bottleneck tests in species showing high variance in reproductive success.
      Particularly in species with high fecundity, computer simulations are recommended
      to confirm the occurrence of a population bottleneck.

PMID- 24131798
TI  - A tale of two ligands: angiopoietins, the endothelium, and outcomes.
AB  - Angiopoietins signal via the Tie-2 receptor and are essential molecules for
      vasculogenesis during development and in the adult state play roles in vascular
      stability as well as inflammation and appear to be involved in the dysregulation
      of the endothelium in illness. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)
      are, respectively, agonists and competitive partial agonists, which have been
      found to undergo alterations in individuals with sepsis. In sepsis, Ang-2 levels
      are elevated and Ang-1 is decreased. In the previous issue of Critical Care,
      Fiusa and colleagues measure circulating Ang-1 and Ang-2 along with other growth
      factors in humans with febrile neutropenia. The authors found that an increased
      Ang-2/Ang-1 ratio, or an elevated Ang-2 level, at the time of an initial fever,
      is associated with subsequent development of septic shock and death. These
      findings validate that the Ang-2/Ang-1 balance, which is thought to reflect
      overall signaling via the Tie-2 receptor, is relevant to outcomes in patients
      with sepsis. Importantly, the specimens were obtained far in advance of the
      development of septic shock, suggesting that detectable alterations in this
      pathway may provide early clues regarding outcomes. This study adds to the
      evidence that angiopoietins are early markers of endothelial dysfunction in
      sepsis and provide prognostic information regarding outcomes. 

PMID- 24131800
TI  - Posterior reversible encephalopathy syndrome in systemic lupus erythematosus
      following methylprednisolone: report of two cases.

PMID- 24131799
TI  - Aging on a different scale--chronological versus pathology-related aging.
AB  - In the next decades the elderly population will increase dramatically, demanding
      appropriate solutions in health care and aging research focusing on healthy aging
      to prevent high burdens and costs in health care. For this, research targeting
      tissue-specific and individual aging is paramount to make the necessary
      progression in aging research. In a recently published study we have attempted to
      make a step interpreting aging data on chronological as well as pathological
      scale. For this, we sampled five major tissues at regular time intervals during
      the entire C57BL/6J murine lifespan from a controlled in vivo aging study,
      measured the whole transcriptome and incorporated temporal as well as physical
      health aspects into the analyses. In total, we used 18 different age-related
      pathological parameters and transcriptomic profiles of liver, kidney, spleen,
      lung and brain and created a database that can now be used for a broad systems
      biology approach. In our study, we focused on the dynamics of biological
      processes during chronological aging and the comparison between chronological and
      pathology-related aging. 

PMID- 24131801
TI  - Patient and prescriber perspectives on long-acting injectable (LAI)
      antipsychotics and analysis of in-office discussion regarding LAI treatment for
      schizophrenia.
AB  - BACKGROUND: The research goal is to better understand prescriber, patient, and
      caregiver perspectives about long-acting injectable (LAI) antipsychotic therapy
      and how these perspectives affect LAI use. Addressing these perspectives in the
      clinic may lead to greater success in achieving therapeutic goals for the patient
      with schizophrenia. METHODS: Ethnographic information was collected from a non
      random sample of 69 prescriber-patient conversations (60 with community mental
      health center [CMHC] psychiatrists; 9 with nurse-practitioners) recorded during
      treatment visits from August 2011 to February 2012, transcribed and analyzed.
      Discussions were categorized according to 11 predetermined CMHC topics. In-person
      observations were also conducted at 4 CMHCs, including home visits by researchers
      (n = 15 patients) prior to the CMHC visit and observations of patients receiving
      injections and interacting with staff. Telephone in-depth interviews with
      psychiatrists, patients, and caregivers to gather additional information on LAI
      discussion, prescription, or use were conducted. RESULTS: Antipsychotic treatment
      decisions were made without patient or caregiver input in 40 of 60 (67%) of
      psychiatrist-patient conversations. Involvement of patients or caregivers in
      treatment decisions was greater when discussing LAI (15 of 60 [25%]) vs oral
      antipsychotic treatment (5 of 60 [8%]). LAIs were not discussed by psychiatrists
      in 11 of 22 (50%) patients taking oral antipsychotics. When offered, more LAI
      naive patients expressed neutral (9 of 19 [47%]) rather than favorable (3 of 19
      [16%]) or unfavorable (7 of 19 [37%]) responses. Prescribers were most concerned
      about potentially damaging the therapeutic relationship and side-effects when
      discussing LAIs while patient resistance was often related to negative feelings
      about injections. Psychiatrists had some success in overcoming patient objections
      to LAIs by addressing and decomposing initial resistance. More than half (11 of
      19 [58%]) of LAI-naive patients agreed to start LAI treatment following office
      visits. Patient-described benefits of LAIs vs orals included perceived rapid
      symptom improvement and greater overall efficacy. CONCLUSIONS: In this study,
      many psychiatrists did not offer LAIs and most patients and caregivers were not
      involved in antipsychotic treatment decision making. Opportunities to increase
      active patient engagement, address resistances, guide patient drug-formulation
      selection, and provide better LAI-relevant information for more individualized
      approaches to treating the patient with schizophrenia were present.

PMID- 24131802
TI  - On the importance of cotranscriptional RNA structure formation.
AB  - The expression of genes, both coding and noncoding, can be significantly
      influenced by RNA structural features of their corresponding transcripts. There
      is by now mounting experimental and some theoretical evidence that structure
      formation in vivo starts during transcription and that this cotranscriptional
      folding determines the functional RNA structural features that are being formed.
      Several decades of research in bioinformatics have resulted in a wide range of
      computational methods for predicting RNA secondary structures. Almost all state
      of-the-art methods in terms of prediction accuracy, however, completely ignore
      the process of structure formation and focus exclusively on the final RNA
      structure. This review hopes to bridge this gap. We summarize the existing
      evidence for cotranscriptional folding and then review the different, currently
      used strategies for RNA secondary-structure prediction. Finally, we propose a
      range of ideas on how state-of-the-art methods could be potentially improved by
      explicitly capturing the process of cotranscriptional structure formation. 

PMID- 24131807
TI  - Secreted proteins from carotid endarterectomy: an untargeted approach to disclose
      molecular clues of plaque progression.
AB  - BACKGROUND: Atherosclerosis is the main cause of morbidity and mortality in
      Western countries and carotid plaque rupture is associated to acute events and
      responsible of 15-20% of all ischemic strokes. Several proteomics approaches have
      been up to now used to elucidate the molecular mechanisms involved in plaque
      formation as well as to identify markers of pathology severity for early
      diagnosis or target of therapy. The aim of this study was to characterize the
      plaque secretome. The advantage of this approach is that secretome mimics the in
      vivo condition and implies a reduced complexity compared to the whole tissue
      proteomics allowing the detection of under-represented potential biomarkers.
      METHODS: Secretomes from carotid endarterectomy specimens of 14 patients were
      analyzed by a liquid chromatography approach coupled with label free mass
      spectrometry. Differential expression of proteins released from plaques and from
      their downstream distal side segments were evaluated in each specimen. Results
      were validated by Western blot analysis and ELISA assays. Histology and
      immunohistochemistry were performed to characterize plaques and to localise the
      molecular factors highlighted by proteomics. RESULTS: A total of 463 proteins
      were identified and 31 proteins resulted differentially secreted from plaques and
      corresponding downstream segments. A clear-cut distinction in the distribution of
      cellular- and extracellular-derived proteins, evidently related to the higher
      cellularity of distal side segments, was observed along the longitudinal axis of
      carotid endarterectomy samples. The expressions of thrombospondin-1, vitamin D
      binding protein, and vinculin, as examples of extracellular and intracellular
      proteins, were immunohistologically compared between adjacent segments and
      validated by antibody assays. ELISA assays of plasma samples from 34 patients and
      10 healthy volunteers confirmed a significantly higher concentration of
      thrombospondin-1 and vitamin D binding protein in atherosclerotic subjects.
      CONCLUSIONS: Taking advantage of the optimized workflow, a detailed protein
      profile related to carotid plaque secretome has been produced which may assist
      and improve biomarker discovery of molecular factors in blood. Distinctive
      signatures of proteins secreted by adjacent segments of carotid plaques were
      evidenced and they may help discriminating markers of plaque complication from
      those of plaque growth.

PMID- 24131808
TI  - Sperm analysis of the vas deferens fluid after a long interval of unilateral
      percutaneous epididymal sperm aspiration in vasectomized patients.
AB  - OBJECTIVES: Evaluation of the presence of spermatozoa in vas deferens fluid after
      a long interval of unilateral and homolateral percutaneous epididymal sperm
      aspiration (PESA) in vasectomized men. When found, the spermatozoa were evaluated
      including concentration and motility, in order to verify the patency of the
      epididymal tubules. MATERIALS AND METHODS: Four patients, numbered in a
      progressive order, from one to four, with 38, 40, 48 and 51 years old and
      vasectomy interval of 10, 10, 25 and 11 years, respectively, whose wives did not
      get pregnant using intracytoplasmic sperm injection of sperm obtained by
      unilateral PESA and decided to try only natural conception, were submitted to
      intrasurgical sperm analysis of the vas deferens fluid (ISAVDF) during
      microsurgery for reconstruction of the seminal tract. RESULTS: Time interval
      between PESA and ISAVDF was 13.75 +/- 11.12 months (x +/- s) varying from 3 to 29
      months. Homolateral ISAVDF and PESA showed the presence of spermatozoa. Patients
      1, 2 and 4 had a high concentration of 10 x 106, 64 x 106 and 45 x 106
      spermatozoa/ mL; the first two had motile sperms and patient 3 had no sperms.
      CONCLUSIONS: Three of four patients showed spermatozoa in the vas deferens fluid
      after a long interval of unilateral and homolateral PESA with high concentration,
      including motile forms. These findings support the concept that PESA may not
      result in late epipidymal tubule obstruction in vasectomized patients.

PMID- 24131809
TI  - Redesigned care must focus on the health needs of Canadians.

PMID- 24131810
TI  - Using evidence to meet population healthcare needs: successes and challenges.
AB  - In order to respond effectively to the health needs of Canadians, healthcare
      planners must directly consider these needs when planning and delivering
      services. However, Canada's various healthcare systems have traditionally been
      organized based on historical levels of service provision as opposed to
      population health needs. A number of innovations in care delivery redesign in
      Canada have already been developed as part of efforts to foster a more effective
      and sustainable healthcare system. This paper presents two of these as case
      studies illustrating some of the main challenges in trying to identify and
      address healthcare needs, as well as some potential solutions to those
      challenges. 

PMID- 24131811
TI  - Is the deck stacked against fundamental health human resources redesign in
      Canada?
AB  - Contemporary healthcare is a sobering spectacle. It costs a lot and doesn't
      deliver much at the margins. But even if deep and open-minded reflection and
      analysis were to propose a reboot, the odds are very long against it. It is next
      to impossible to alter deeply entrenched patterns and entitlements. It will take
      nothing less than a collective commitment on the part of professions,
      governments, educators, accreditors, employers and a whole host of others to
      create an agile, responsive and integrated health human resources model for
      Canada. 

PMID- 24131812
TI  - Policy and evidence in Canadian health human resources planning.
AB  - The health human resources supply in Canada swings reactively between over- and
      under-supply. There are numerous policy actors in this arena, each of whom could
      contribute to good data collection and an agreed-on process for decision-making.
      This could form the basis for evidence-informed policy. Absent these tools for
      pan-Canadian health human resources policy development, smaller health
      jurisdictions are experimenting with quality improvement initiatives which, when
      properly evaluated, can discover useful methods of aligning patient and community
      needs with healthcare resources. 

PMID- 24131813
TI  - The importance of evaluating new models of care to better meet patient needs.
AB  - In their paper "Using evidence to meet population healthcare needs: successes and
      challenges," Tomblin Murphy and MacKenzie highlight the critically important need
      to shift health system reform efforts from those focused on the more salient
      provider or supply side to those that more appropriately attempt to better meet
      patient and population health needs. A population needs-based focus on health
      workforce planning that is more than just rhetoric is indeed important, as is
      acknowledging that population health needs are best addressed through an
      interdisciplinary approach to care. Most importantly, the authors also argue that
      rigorous evaluation is needed to scale up the most promising health workforce
      innovations: this could be best addressed with a dedicated arm's-length health
      workforce evidence infrastructure.

PMID- 24131814
TI  - Successes and challenges: clarity of definition required.
AB  - In the lead paper, Tomblin Murphy and MacKenzie advocate the application of
      population health needs in the planning and delivery of clinical services across
      Canadian healthcare systems. The authors are correct in urging the minimal use,
      if not abandonment, of legacy demand data as a relevant predictor for advancing a
      more effective and sustainable healthcare system. The primary challenge for a
      reader of their paper is the confusion of terminology and a resulting dissonance
      among the title, the abstract and the content. Expectations created by the title
      are not attained due to the unfortunate interchangeability of key phrases and the
      propriety of the case studies selected as examples. This commentary focuses on
      the choice of language and concerns of secondary uncertainty between "needs" and
      process management; this is framed by a brief review of terminology and the
      principles that underpin needs-based models. 

PMID- 24131815
TI  - Using evidence to meet population healthcare needs: A UK perspective.
AB  - For over 30 years, researchers have questioned the standard practice of planning
      the health workforce, with relatively little effect on policy. The authors of
      this commentary find it extremely refreshing and thoroughly heartening to see
      their Canadian colleagues making new attempts to change the way that the health
      workforce is planned and structured. In this commentary, the authors discuss what
      is meant by healthcare "needs" and the traditionally poor use of data in
      healthcare planning, and they support Tomblin Murphy and MacKenzie's call for
      proper evaluation of healthcare resources interventions. 

PMID- 24131816
TI  - More for less - if only we could get them to do it!
AB  - Systems for the provision of healthcare need to be improved, since costs are
      already high and rising along with the needs of an aging population. In
      considering evaluations of two programs from opposite ends of the country,
      inferences can differ depending on the observer. While the demographic-healthcare
      time bomb we're faced with should have been obvious years ago, the need for
      positive action is upon us. The difficult issues are not so much errors in the
      past as they are (1) disingenuous suggestions that this isn't a cost problem, (2)
      a need to improve team behaviors and functions to increase the value of the care
      provided (i.e., quality for expenditure), (3) a lack of engagement and enthusiasm
      by providers for new systems and (4) most importantly, resistance to change
      brought from outside the care environment and the source and beneficiaries of the
      change not being primarily the local stakeholders. Care providers and recipients,
      as well as the governments funding healthcare will need to be convinced that we
      are successfully increasing healthcare value and improving patient outcomes. 

PMID- 24131818
TI  - Quality of life and associated factors in persons with chronic rhinosinusitis in
      the general population: a prospective questionnaire and clinical cross-sectional
      study.
AB  - OBJECTIVES: The European Position Paper on Rhinosinusitis and Nasal Polyps
      describes methods to perform population-based and clinical studies on chronic
      rhinosinusitis in a standardised way, and it also describes how to clinical
      investigate CRS. The aim of this cross-sectional study was to evaluate quality of
      life and objective findings in persons with chronic rhinosinusitis recruited from
      the general population. DESIGN: As part of a trans-European study, selected
      respondents to a survey questionnaire were invited for a clinical visit.
      Subjective symptoms and rhinoscopy were used for the clinical diagnosis of
      chronic rhinosinusitis, and persons with and without chronic rhinosinusitis were
      compared. SETTING: This research took place in the department of Otolaryngology,
      Odense University Hospital. PARTICIPANTS: A total of 366 persons participated at
      the clinical visit, and of these, 91 were diagnosed with chronic rhinosinusitis,
      271 without chronic rhinosinusitis and four persons were excluded. MAIN OUTCOME
      MEASURES: Severity of symptoms and disease-specific quality of life were measured
      using the Sino-Nasal Outcome Test 22, and generic quality of life was measured
      using European quality of life - 5 dimensions including an index score and a
      visual analogue scale. RESULTS: The prevalence of chronic rhinosinusitis was 9%,
      and the prevalence of polyps was 4%. Persons with chronic rhinosinusitis had
      significantly reduced disease-specific quality of life (P = 0.00) and generic
      quality of life (P = 0.04 and 0.01) compared with persons without chronic
      rhinosinusitis. Having chronic rhinosinusitis was correlated to age, allergic
      rhinitis and smell. CONCLUSION: This study gives insight into health-related
      quality of life and objective findings in persons with chronic rhinosinusitis
      recruited from the general population.

PMID- 24131819
TI  - An investigation of resistance to beta-lactam antimicrobials among staphylococci
      isolated from pigs with exudative epidermitis.
AB  - BACKGROUND: A high proportion of staphylococci isolated from pigs affected with
      exudative epidermitis were found to be resistant to beta-lactam antimicrobials.
      The primary objective of this research was to investigate and characterize beta
      lactam resistance in Staphylococcus hyicus, Staphylococcus aureus and other
      staphylococci isolated from these pigs. RESULTS: The antimicrobial resistance
      patterns of 240 staphylococci isolates were determined by disk diffusion, of
      which 176 (73.3%) of the isolates were resistant to 3 beta-lactams (penicillin G,
      ampicillin, and ceftiofur). The presence of mecA gene was identified in 63
      staphylococci isolates from skin samples by PCR. The mecA gene was identified in
      19 S. aureus, 31 S. hyicus, 9 Staphylococcus chromogenes, 2 Staphylococcus
      pseudintermedius isolates, and in 1 isolate each of Staphylococcus arlettae, and
      Staphylococcus cohnii subspecies urealyticus. From SCCmec typing results, the
      majority (45/63, 71.4%) were shown to be SCCmec type V. One isolate was SCCmec
      III. Fourteen isolates were detected as mec class A, mec class C or ccr type 5.
      The ccr complex and mec complex was not detected in 3 isolates of methicillin
      resistant S. hyicus (MRSH) based on multiplex PCR. Of the 30 isolates of MRSA
      identified from nasal samples of the pigs, 29 isolates were SCCmec type V and 1
      isolate was SCCmec type II. Staphyloccoci isolates that were mecA negative but
      resistant to beta-lactam antimicrobials were further examined by screening for
      mecC, however all were negative. Furthermore, the majority of mecA negative beta
      lactam resistant staphylococci isolates were susceptible to oxacillin and
      amoxicillin-clavulanic acid in a double disk diffusion test. CONCLUSIONS:
      Methicillin resistance can be identified in a variety of staphylococcal species
      isolated from pigs. In this study there was a great deal of similarity in the
      SCCmec types between staphylococcal species, suggesting that resistance may be
      passed from one species of staphylococci to another species of staphylococci.
      While this has been reported for acquisition of methicillin-resistance from
      coagulase negative staphylococci to S. aureus, these data suggest that
      transmission to or from the porcine pathogen S. hyicus may also occur. The
      identification of methicillin resistance in a variety of staphylococcal species
      in pigs does raise concerns about the spread of serious multi-drug resistance in
      food producing animals and warrants further study.

PMID- 24131820
TI  - Hand bone mineral density reference values in a Turkish healthy female
      population.
AB  - AIM: In this study we aimed at identifying the bone mineral density (BMD)
      reference values of hands, according to age, measured by dual-energy X-ray
      absorptiometry (DEXA) and assessing the correlation of these values with lumbar
      and femoral BMD values. METHOD: A total of 403 healthy women aged between 20 and
      70 participated in our study. All BMD measurements are performed by DEXA method
      on both hands, anteroposterior lumbar spine (L2-L4) and right femur (femoral
      neck, total femur) regions. BMD results of all the patients were divided to 10
      year age categories and evaluated in five subgroups in total (20-30 to 61-70).
      RESULTS: Among the 10-year age categories we found both dominant and non-dominant
      hand peak bone mass values in the 31-40 years age group (0.423 +/- 0.039 g/cm2,
      0.410 +/- 0.043 g/cm2, respectively). Statistically significant positive
      correlation was defined between dominant and non-dominant hand BMD values and L2
      L4 spine, femur neck and total femur values (for dominant hand r = 0.636, P =
      0.0001; r = 0.645, P = 0.0001; r = 0.623; P = 0.0001; for non-dominant hand r =
      0.624, P = 0.0001; r = 0.637, P = 0.0001, r = 0.623, P = 0.0001, respectively).
      Regarding the relationship of age and menopause with BMD results, a negative
      statistical relationship was observed among dominant and non-dominant hand, L2-L4
      spine, femoral neck and total femur BMD values (P = 0.0001). CONCLUSION: Our
      study has provided hand BMD reference values in women aged between 20-70 years;
      further studies are needed to investigate the role of these values in identifying
      diseases causing osteoporosis in the hand and in evaluating treatment.

PMID- 24131822
TI  - An expanded role for semaphorin 4D in platelets includes contact-dependent
      amplification of Clec-2 signaling.

PMID- 24131821
TI  - Defining structural and evolutionary modules in proteins: a community detection
      approach to explore sub-domain architecture.
AB  - BACKGROUND: Assessing protein modularity is important to understand protein
      evolution. Still the question of the existence of a sub-domain modular
      architecture remains. We propose a graph-theory approach with significance and
      power testing to identify modules in protein structures. In the first step,
      clusters are determined by optimizing the partition that maximizes the modularity
      score. Second, each cluster is tested for significance. Significant clusters are
      referred to as modules. Evolutionary modules are identified by analyzing
      homologous structures. Dynamic modules are inferred from sets of snapshots of
      molecular simulations. We present here a methodology to identify sub-domain
      architecture robustly, biologically meaningful, and statistically supported.
      RESULTS: The robustness of this new method is tested using simulated data with
      known modularity. Modules are correctly identified even when there is a low
      correlation between landmarks within a module. We also analyzed the evolutionary
      modularity of a data set of alpha-amylase catalytic domain homologs, and the
      dynamic modularity of the Niemann-Pick C1 (NPC1) protein N-terminal domain.The
      alpha-amylase contains an (alpha/beta)8 barrel (TIM barrel) with the
      polysaccharides cleavage site and a calcium-binding domain. In this data set we
      identified four robust evolutionary modules, one of which forms the minimal
      functional TIM barrel topology.The NPC1 protein is involved in the intracellular
      lipid metabolism coordinating sterol trafficking. NPC1 N-terminus is the first
      luminal domain which binds to cholesterol and its oxygenated derivatives. Our
      inferred dynamic modules in the protein NPC1 are also shown to match functional
      components of the protein related to the NPC1 disease. CONCLUSIONS: A domain
      compartmentalization can be found and described in correlation space. To our
      knowledge, there is no other method attempting to identify sub-domain
      architecture from the correlation among residues. Most attempts made focus on
      sequence motifs of protein-protein interactions, binding sites, or sequence
      conservancy. We were able to describe functional/structural sub-domain
      architecture related to key residues for starch cleavage, calcium, and chloride
      binding sites in the alpha-amylase, and sterol opening-defining modules and
      disease-related residues in the NPC1. We also described the evolutionary sub
      domain architecture of the alpha-amylase catalytic domain, identifying the
      already reported minimum functional TIM barrel.

PMID- 24131824
TI  - Hen's egg, not cow's milk, sensitization in infancy is associated with asthma: 10
      year follow-up of the PIAMA birth cohort.

PMID- 24131823
TI  - Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in
      patients with common variable immunodeficiency.
AB  - BACKGROUND: Despite reducing pneumonia and other infections, antibody replacement
      does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with
      common variable immunodeficiency (CVID). The pathogenesis and optimal treatments
      remain to be clarified. OBJECTIVE: We aimed to better understand the pathology of
      CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of
      interstitial lung disease associated with autoimmune diseases, has not previously
      been explored in patients with CVID. METHODS: We examined the clinical
      characteristics and pathologic findings of 6 patients with CVID with
      nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH.
      RESULTS: In these subjects regions of PLH contained distinct B- and T-cell zones,
      with B-cell predominance in 1 patient and T-cell predominance in the others.
      Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture
      demonstrated tertiary lymphoneogenesis with active centers of cellular
      proliferation. One patient received rituximab with improved pulmonary radiologic
      findings. CONCLUSION: Ectopic lymphoid tissue forming germinal centers suggest
      tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted
      therapy might disrupt CVID-associated lymphoid hyperplasia.

PMID- 24131825
TI  - GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids
      in white subjects with asthma.

PMID- 24131826
TI  - Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm
      infants: a randomized, placebo-controlled trial.
AB  - BACKGROUND: Simple and safe strategies for the prevention of viral respiratory
      tract infections (RTIs) are needed. OBJECTIVE: We hypothesized that early
      prebiotic or probiotic supplementation would reduce the risk of virus-associated
      RTIs during the first year of life in a cohort of preterm infants. METHODS: In
      this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no.
      NCT00167700), 94 preterm infants (gestational age, >=32 + 0 and <=36 + 6 weeks;
      birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were
      allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose
      mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo
      (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome
      was the incidence of clinically defined virus-associated RTI episodes confirmed
      from nasal swabs by using nucleic acid testing. Secondary outcomes were the
      severity and duration of RTIs. RESULTS: A significantly lower incidence of RTIs
      was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12
      0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared
      with those receiving placebo. Also, the incidence of rhinovirus-induced episodes,
      which comprised 80% of all RTI episodes, was found to be significantly lower in
      the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49;
      95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No
      differences emerged among the study groups in rhinovirus RNA load during
      infections, duration of rhinovirus RNA shedding, duration or severity of
      rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants.
      CONCLUSIONS: Gut microbiota modification with specific prebiotics and probiotics
      might offer a novel and cost-effective means to reduce the risk of rhinovirus
      infections.

PMID- 24131827
TI  - Chorea, a little-known manifestation in systemic lupus erythematosus: short
      literature review and four case reports.
AB  - Chorea is a movement disorder that may be found in children due to several
      causes. Here we focus especially on Systemic Lupus Erythematosus associated
      chorea. First we outline its epidemiology, hypothesized pathogenesis, clinical
      presentation and treatment, then we report four significant clinical cases, which
      represent well the extreme variability of set of symptoms that may accompany
      lupus chorea. Our experience, according to literature, suggests that choreic
      movements in a child should alert the pediatrician and lead him to investigate a
      potential neurological involvement of Systemic Lupus Erythematosus. 

PMID- 24131828
TI  - [Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an
      eternal topic].
AB  - Pulmonary arterial hypertension (PAH) is one of the most severe complications of
      congenital heart defects with left to right shunt. Pulmonary vascular remodeling
      (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR
      is one of the most important factors for improving quality of life for children
      suffering from PAH. In this article we reviewed the emerging research views on
      PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections
      were included. On the one hand, we introduced the "ATM signal turning point
      hypothesis" from the DNA damage response (DDR) mechanism research in oncology.
      The hypothesis suggests that the tumor-like proliferation of vascular smooth
      muscle cells might be the pathological basis of obstructive PAH. On the other
      hand, a new lung-targeted drug delivery system based on the fact that low
      concentration of anti-tumor drugs can inhibit angiogenesis without cellular
      toxicity was introduced. These new research directions could extend current
      practice in PVR therapy. 

PMID- 24131829
TI  - [Long term psychosocial outcomes of congenital heart disease in adolescents and
      young adults].
AB  - OBJECTIVE: Congenital heart disease (CHD) is a chronic illness with a high
      frequency in the worldwide population, and is normally diagnosed at birth or in
      uterus. Because of better conditions in diagnosis and early medical and surgical
      treatment, patients have survival rates of 90% and go further and further in
      life, facing different challenges in life cycle. In this study, we tested the
      effects of different demographic, clinical and psychosocial variables on the
      perception of quality of life (QOL), on psychosocial adjustment (PSA) and
      psychiatric morbidity (PM) of adolescents and young adults with CHD. We aimed to
      evaluate QOL, PM and PSA of adolescents and young adults with CHD and to
      determine which variables (demographic, clinical, and psychosocial) play a role
      in buffering stress and promoting resilience and which ones have a detrimental
      effect. METHODS: The study enrolled 150 CHD patients (87 males and 63 females),
      12 to 26 years (17.45+/-3.373 years). The participants were interviewed regarding
      social support, family educational style, self-image, demographic information and
      physical limitations. They responded to questions in a standardized psychiatric
      interview (SADS-L) and completed self-reports questionnaires for assessment of
      QOL (WHOQOL-BREF) and PSA (YSR/ASR). RESULTS: We found a 18.7% lifetime
      prevalence of psychopathology in our participants (25.4% in females and 13.8% in
      males). 57.1% had retentions in school (1.53+/-0.804 year). The perception of QOL
      of CHD patients is better compared to the Portuguese population in the social
      relationships, environmental, physical and general dimensions. However, it is
      worse in female CHD patients and patients with poor academic performance and
      social support as well as in patients with complex or cyanotic CHD, moderate-to
      severe residual lesions and physical limitations, and undergoing surgery. All of
      these variables, except presence of cyanosis, are also associated to a worse PSA.
      CONCLUSIONS: Female patients and patients with poor academic performance and poor
      social support refer worse PSA and QOL.

PMID- 24131830
TI  - [Histone acetylation and expression of acetylation-related enzymes in children
      with tetralogy of Fallot].
AB  - OBJECTIVE: To study the expression of histone acetyltransferases (HATs) and
      histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to
      investigate the role of histone acetylation and acetylation-related enzymes in
      the pathogenesis of TOF. METHODS: Myocardial tissue samples in the TOF group were
      obtained from 46 children with TOF who underwent radical operation, and
      myocardial tissue samples in the control group were obtained from 16 children who
      suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The
      acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The
      mRNA expression of HATs and HDACs in the myocardium was measured by real-time
      PCR. The correlation between mRNA expression of HATs and HDACs and histone
      acetylation was analyzed. RESULTS: Compared with the control group, the TOF group
      showed significantly increased acetylation of H3K9 (P=0.0165) and significantly
      decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and
      6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF
      group than in the control group (P=0.025; P=0.017), and there was no significant
      difference in the mRNA expression of other HATs and HDACs between the two groups.
      The correlation analysis revealed a positive correlation between H3K9 acetylation
      and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).
      CONCLUSIONS: Upregulated mRNA expression of EP300 and CBP may be associated with
      increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac
      development by regulating H3K9 acetylation.

PMID- 24131831
TI  - [Association between two SNPs of ISL1 gene and congenital heart disease in
      children].
AB  - OBJECTIVE: To investigate the association between 2 SNPs of ISL1 gene and
      congenital heart disease (CHD) in Tianjin Han children. METHODS: Polymerase chain
      reaction and DNA sequencing were used to detect 2 SNPs at rs41268421 and rs1017
      sites of ISL1 gene, including 35 CHD cases and 30 non-CHD controls. Differences
      of genotype and allele frequencies of rs41268421 and rs1017 sites were compared,
      and haplotype analysis of the two sites was performed. RESULTS: Three genotypes
      (GG, GT and TT) were detected at ISL1 gene SNP rs41268421, and three genotypes
      (AA, AT and TT) were detected at SNP rs1017. At rs41268421, GT+TT genotypes and T
      allele frequencies in the CHD group were statistically higher than in the
      controls. The risk of CHD in children with T allele was significantly increased
      compared with children with G allele (OR=4.833). At rs1017, AT+TT genotypes and T
      allele frequencies in the CHD group were statistically higher than controls. The
      risk of CHD in children with T allele was greater compared with children with A
      allele (OR=4.491; P<0.05). Four kinds of haplotype were detected in the two SNPs
      sites and TT type increased the risk of CHD (OR=7.813). CONCLUSIONS: Haplotype TT
      may increase the risk of CHD in Tianjin Han children.

PMID- 24131832
TI  - [Perioperative change in serum neutrophil gelatinase-associated lipocalin level
      among children with congenital heart disease and pulmonary hypertension].
AB  - OBJECTIVE: To study the perioperative change in serum neutrophil gelatinase
      associated lipocalin (NGAL) level among children with congenital heart disease
      (CHD) and pulmonary hypertension (PH) and its significance. METHODS: Eighty
      children with CHD were divided into four groups according to pulmonary artery
      systolic pressure: non-PH, mild PH, moderate PH and severe PH groups. Serum NGAL
      levels were measured before operation, immediately after operation and 24 hours
      after operation. The relationship of serum NGAL level with PH and early prognosis
      was analyzed. RESULTS: The mild, moderate and severe PH groups had significantly
      higher serum NGAL levels than the non-PH group, and the severer the PH, the
      higher the serum NGAL level (P<0.01). All groups showed significant decreases in
      serum NGAL levels after operation (P<0.01). Serum NGAL level was positively
      correlated with the degree of PH and length of stay in the intensive care unit
      (P<0.01). CONCLUSIONS: Serum NGAL level increases in children with CHD and PH,
      and it gradually decreases after operation for closing the abnormal shunt. Serum
      NGAL level may be used as a serological indicator for evaluating the degree of PH
      and surgical outcome.

PMID- 24131833
TI  - [Risk factors for accelerated junctional escape rhythm in children early after
      percutaneous ventricular septal defect closure].
AB  - OBJECTIVE: To identify the risk factors for accelerated junctional escape rhythm
      (AJER) in children early after percutaneous ventricular septal defect (VSD)
      closure. METHODS: A retrospective controlled study was conducted on 42 children
      who had AJER within one week after percutaneous VSD closure between January 2008
      and October 2012. These subjects were compared with controls without AJER after
      VSD closure in terms of age, sex, diameter of VSD, occluder size, difference
      between occluder size and diameter of VSD, and distance between VSD and aortic
      valve ring. Risk factors for AJER were identified by logistic regression
      analysis. RESULTS: Compared with the control group, the AJER group had a longer
      distance betweenVSD and aortic valve ring, a larger diameter of VSD (basal
      diameter), a larger occluder size (waist diameter) , and a bigger difference
      between the waist diameter of occluder and diameter of VSD (P<0.05). Logistic
      regression analysis showed that distance between VSD and aortic valve ring
      (OR=1.813, P<0.05) and occluder size (OR=1.671, P<0.05) are primary risk factors
      for AJER. CONCLUSIONS: AJER early after percutaneous VSD closure is related to
      diameter of VSD, occluder size, difference between the waist diameter of occluder
      and diameter of VSD, and distance between VSD and aortic valve ring. The distance
      between VSD and aortic valve ring and occluder size are primary risk factors for
      AJER.

PMID- 24131834
TI  - [Visualization study of current research on nutrition of premature infants in
      China].
AB  - OBJECTIVE: Inadequate postnatal nutritional support is an important factor
      contributing to growth failure, which leads to poor neurological outcome. In this
      study, co-word analysis was used to investigate the research on nutrition of
      premature infants over the last six years in China, describe the research trend
      in this field in China, and provide possible directions for future research.
      METHODS: A literature search was performed in January 2013 using the CNKI
      database and the key words "preterm infant" and "nutrition". A total of 772
      articles were retrieved. Then high-frequency key words were extracted using Excel
      2010 to create a co-occurrence matrix. Finally, a visualized network was built
      using Ucinet 6.0. RESULTS: The knowledge domain map of research on nutritional
      support for premature infants in China showed that the major topic of relevant
      research is still the combination of parenteral nutrition and enteral nutrition,
      with the goal of maintaining appropriate growth rates in premature infants.
      Researchers have paid much attention to the adverse effects of parenteral
      nutrition. Feeding intolerance is still the main problem in nutritional support,
      especially enteral nutrition, for premature infants. CONCLUSIONS: A visualized
      network of current research on nutrition of premature infants in China has been
      created, and a knowledge domain map has been drawn to reflect the hot topics in
      this field of study over the last six years.

PMID- 24131835
TI  - [Changes in plasma thrombomodulin and D-dimer levels and their clinical
      significance in neonates with sepsis].
AB  - OBJECTIVE: To observe changes in plasma thrombomodulin (TM) and D-dimer (DD)
      levels in neonates with sepsis, and to investigate their significance in
      evaluating the patients' condition and prognosis. METHODS: Fifty-six neonates
      with sepsis were classified into extremely critical (n=13), critical (n=22) and
      non-critical groups (n=21) based on neonatal critical illness score (NCIS).
      Fasting venous blood samples were collected on admission and in the recovery
      phase. Plasma TM and D-dimer levels were measured using enzyme-linked
      immunosorbent assay and immune turbidimetry, respectively. Twenty-six healthy
      neonates were selected as the control group. Plasma TM and D-dimer levels were
      compared between groups, and the changes after treatment were determined.
      RESULTS: Plasma TM levels in the extremely critical, critical and non-critical
      groups were 25.5+/-6.6, 17.3+/-4.7 and 13.3+/-2.8 ug/L respectively,
      significantly higher than in the control group (9.8+/-2.7 ug/L) (P<0.01). Plasma
      D-dimer levels in the extremely critical and critical groups were 744+/-262 and
      436+/-147 ug/L respectively, also significantly higher than in the control group
      (205+/-61 ug/L) (P<0.01). The extremely critical group had significantly higher
      plasma TM and DD levels than the critical group (P<0.05), and the critical group
      had significantly higher plasma TM and DD levels than the non-critical group
      (P<0.05). All patients showed significant decreases in plasma TM and DD levels in
      the recovery phase after treatment (P<0.01). Plasma TM and DD levels were
      significantly negatively correlated with NCIS (r=-0.428, P<0.01; r=-0.363,
      P<0.01). CONCLUSIONS: Determination of plasma TM and DD levels may be helpful in
      evaluating severity and prognosis in neonates with sepsis.

PMID- 24131836
TI  - [Clinical analysis of 28 cases of bronchiolitis obliterans].
AB  - OBJECTIVE: To study the clinical features of bronchiolitis obliterans (BO) in
      children. METHODS: The clinical data of 28 children with BO between July 2007 and
      April 2012 was retrospectively reviewed. RESULTS: All patients presented with
      persistent or repeated cough and wheezing. Twenty-three cases were post
      infectious bronchiolitis obliterans (PIBO), among whom the etiology were
      adenovirus (12 cases), measles (2 cases), influenza virus A (2 cases), mycoplasma
      pneumoniae (1 case), mycoplasma pneumoniae coinfection with adenovirus (1 case),
      respiratory syncytial virus coinfection with Parainfluenza type 3 virus (1 case)
      and pulmonary tuberculosis (1 case). The etiology of 3 cases was not associated
      with infection. The etiology was unknown in 2 cases. Pulmonary HRCT revealed that
      decreased density in 25 cases, mosaic perfusion in 21 cases, bronchial wall
      thickening in 15 cases, bronchiectasis in 12 cases and air retention in 6 cases.
      Lung function test was performed on 21 cases and demonstrated that obstructive
      ventilation disorder in all 21 cases. Bronchodilation test was performed on 18
      cases and 17 cases showed a negative result. All 28 cases received corticosteroid
      treatment, and 24 cases were orally administered with low doses of azithromycin.
      One case died during hospitalization. Eighteen cases were followed up for 4
      months to 4 years and seven months. Clinical manifestations were improved in 12
      cases and one case died. CONCLUSIONS: Low respiratory infection is the most
      common cause of pediatric BO and adenovirus is a major pathogen. Persistent
      wheezing and cough were main clinical manifestations. Pulmonary HRCT imaging is
      important for diagnosis and follow-up of BO. Lung function test can typically
      show obstructive ventilation disorder. Corticosteroid and methotrexate may be
      effective for treatment of BO. Prognosis of this disease is unsatisfactory. Early
      diagnosis and treatment, and avoidance of repeated respiratory tract infection
      may be helpful to improve the prognosis.

PMID- 24131837
TI  - [Effect of low-dose methylprednisolone on serum TNF-alpha level in children with
      Mycoplasma pneumoniae pneumonia].
AB  - OBJECTIVE: To investigate the effect of low-dose methylprednisolone on serum
      tumor necrosis factor alpha (TNF-alpha) level in children with Mycoplasma
      pneumoniae pneumonia (MPP). METHODS: A case-control study was conducted among 38
      children with MPP who received treatment in the Affiliated Hospital of Yan'an
      University between January and December 2012, and who had not received
      glucocorticoids before hospitalization. They were randomly divided into
      methylprednisolone treatment (n=20) and conventional treatment groups (n=18). The
      methylprednisolone treatment group was administered with methylprednisolone (1
      mg/kg.d) by intravenous drip for three days in addition to conventional
      treatment. Serum samples were collected from both groups before treatment and on
      days 4 and 7 of treatment. Twenty-five children who underwent physical
      examination in the healthcare clinic during the same period were randomly
      selected as a normal control group, and serum samples were collected on the same
      day that the physical examination was performed. Serum TNF-alpha levels in the
      three groups were measured using enzyme-linked immunosorbent assay. RESULTS: On
      admission, the methylprednisolone treatment and conventional treatment groups had
      significantly higher serum TNF-alpha levels than the normal control group
      (P<0.01), but there was no significant difference between the methylprednisolone
      treatment and conventional treatment groups. On days 4 and 7 of treatment, the
      methylprednisolone treatment group had significantly lower serum TNF-alpha levels
      than the conventional treatment group (P<0.05; P<0.01). On day 7 of treatment,
      there was no significant difference in serum TNF-alpha level between the
      methylprednisolone treatment and normal control groups, but the conventional
      treatment group still had a significantly higher serum TNF-alpha level than the
      normal control group (P<0.01). CONCLUSIONS: Low-dose methylprednisolone can
      significantly decrease serum TNF-alpha level and inhibit inflammatory response in
      children with MPP, and may reduce damage caused by inflammatory response.

PMID- 24131838
TI  - [Impact factors for efficacy of specific immunotherapy in children with dust mite
      allergic asthma].
AB  - OBJECTIVE: To investigate impact factors for the efficacy of specific
      immunotherapy (SIT) in children with dust mite allergic asthma. METHODS: Ninety
      nine children with house dust mite allergic asthma received standardized SIT, and
      the level of asthma control was evaluated after 6 months (S1 stage), 12 months
      (S2 stage), 18 months (S3 stage), and 24 months (S4 stage) of treatment. The age
      of first visit, course of asthma, level of asthma severity, initial serum
      specific immunoglobulin E (sIgE) level, combination with allergic rhinitis or
      atopic dermatitis, use of inhaled corticosteroids, and local or systemic side
      effects during treatment were recorded, and their impacts on the level of asthma
      control were analyzed. RESULTS: As the SIT proceeded, the number of clinically
      controlled cases increased significantly (P<0.01). The level of asthma control
      was significantly affected by the age of patients at first visit in S1 and S3
      stages, and combination with allergic rhinitis or atopic dermatitis in S1 stage
      (P<0.05). In all stages of SIT, the controlled cases had significantly higher
      initial serum sIgE levels than the uncontrolled cases (P<0.05). In S1 and S2
      stages, there was a significantly higher proportion of controlled cases among
      children with a high level of asthma severity than among those with a low level
      of asthma severity (P<0.05). CONCLUSIONS: There is a positive correlation between
      long-term efficacy of SIT and the course or the total dose of treatment. Patients
      with higher initial serum sIgE levels achieve clinical control earlier than those
      with lower initial serum sIgE levels during SIT.

PMID- 24131839
TI  - [Transplantation of human neural precursor cells in the treatment of children
      with pervasive developmental disorder].
AB  - OBJECTIVE: To assess the efficiency and safety of human neural progenitor cells
      (hNPCs) transplantation in the treatment of pervasive developmental disorder
      (PDD) in children. METHODS: Twenty-two children with PDD were treated, including
      13 children with Rett syndrome and 9 children with autism. They accepted hNPCs
      transplantation voluntarily. hNPCs derived from aborted fetal tissue were
      injected into the lateral ventricle of the patients under supersonic guidance.
      All patients were assessed according to the Autism Behavior Checklist before
      operation, at one and six months post operation, and one year later. RESULTS: No
      delayed complications resulting from this therapy were observed. The clinical
      symptoms of 17 patients, including 8 patients with autism and 9 patients with
      Rett syndrome, improved in varying degrees. The assessment results of the Autism
      Behavior Checklist for children with autism showed that compared with pre
      operative function, social communication scores were significantly reduced at six
      months after transplantation, and total scores and social communication and
      language scores were also significantly reduced 1 year after transplantation
      (P<0.05). CONCLUSIONS: These results suggest that hNPCs transplantation is
      effective and safe for treatment of PPD in children. It deserves a further study.

PMID- 24131840
TI  - [Effects of sleep deprivation on the intelligence structure of school-age
      children in Changsha, China].
AB  - OBJECTIVE: To investigate the effects of sleep deprivation on intelligence
      development in primary school students. METHODS: Between June 2009 and April
      2010, 316 grade 5 students aged 10-11 years were selected from four primary
      schools in four administrative districts of Changsha, China by stratified random
      sampling. The intelligence characteristics of children with varying degrees of
      sleep deprivation were investigated using the Chinese Wechsler Intelligence Scale
      for Children. RESULTS: A total of 286 valid questionnaires were received, with a
      response rate of 90.5%. The survey was comprised of a sleep deprivation group
      (sleep time <8 hours per night; n=180) and a control group (sleep time >=8 hours
      per night; n=106). The sleep deprivation group had significantly lower subtest
      scores, verbal intelligence quotient (IQ) (VIQ), performance IQ (PIQ) and full
      scale IQ (P<0.05) and significantly lower verbal comprehension factor score and
      memory/attention factor score compared with the control group (P<0.05). Compared
      with the control group, the moderate sleep deprivation subgroup had significantly
      decreased VIQ and full scale IQ as well as verbal comprehension factor score and
      memory/attention factor score (P<0.05), and the severe sleep deprivation subgroup
      showed decreases in all scores (P<0.05). The sleep deprivation group and moderate
      and severe sleep deprivation subgroups had significantly higher proportions of
      children with VIQ-PIQ imbalance than the control group. CONCLUSIONS: Sleep
      deprivation adversely affects intelligence development, especially VIQ, in
      primary school students, and the adverse effects of sleep deprivation are mainly
      seen in students with moderate and severe sleep deprivation.

PMID- 24131841
TI  - [Relationship of serum 25-hydroxyvitamin D with obesity and inflammatory
      cytokines in children].
AB  - OBJECTIVE: To study the relationship of serum 25-hydroxyvitamin D [25-(OH)D3]
      level with obesity and inflammatory cytokines in children, and to provide a basis
      for clinical evaluation of the relationship between vitamin D nutritional status
      and obesity. METHODS: Seventy-eight children with obesity who visited the
      hospital between February and June 2012 were selected as subjects. According to
      baseline data, such as age and sex, 105 children who underwent physical
      examination in the same period were selected as controls. Fasting venous blood
      samples were taken to measure serum levels of 25-(OH)D3, interleukin-6 (IL-6),
      interleukin-8 (IL-8), interferon-gamma (IFN-gamma), and tumor necrosis factor
      alpha (TNF-alpha). RESULTS: Serum 25-(OH)D3 levels were significantly lower in
      the obesity group than in the control group (P<0.01). Serum 25-(OH)D3 levels were
      negatively correlated with BMI (r=-0.462, P<0.01). Patients were further divided,
      according to their serum 25-(OH)D levels, into vitamin D sufficiency, vitamin D
      insufficiency, vitamin D deficiency and severe vitamin D deficiency subgroups.
      There were significant differences in serum IFN-gamma levels among the subgroups
      (P<0.05). There were no significant differences in serum IL-6, IL-8 and TNF-alpha
      levels between the subgroups, however (P>0.05). CONCLUSIONS: Obese children have
      lower serum 25-(OH)D3 levels than normal children. Serum 25-(OH)D3 level is
      negatively correlated with BMI, but has little correlation with inflammatory
      cytokines levels.

PMID- 24131842
TI  - [Nutritional risk screening and its clinical significance in 706 children
      hospitalized in the surgical department].
AB  - OBJECTIVE: To investigate nutritional risk and its relationship with clinical
      outcome in children hospitalized in the surgical department, and to provide a
      scientific basis for clinical nutrition management. METHODS: Nutritional risk
      screening was performed on 706 children hospitalized in the surgical department
      using the Screening Tool for Risk on Nutritional Status and Growth. The data on
      nutritional support during hospitalization, incidence of infectious
      complications, length of hospital stay, post operative length of hospital stay
      and total hospital expenses were recorded. RESULTS: Of the 706 cases, 11.5% had
      high nutritional risk, 46.0% had moderate nutritional risk, and 42.5% had low
      nutritional risk. Congenital hypertrophic pyloric stenosis, intestinal
      obstruction and congenital heart disease were the three most common types of high
      nutritional risk. The incidence of high nutritional risk was significantly higher
      in infants than in other age groups (P<0.01). Fifty-two (64.2%) of the eighty-one
      children with high nutritional risk received parenteral nutrition. Children with
      high nutritional risk were significantly more likely to have weight loss than
      children with low nutritional risk (P<0.05). Children with high nutritional risk
      had significantly increased incidence of infectious complications, length of
      hospital stay, post operative length of hospital stay and total hospital expenses
      compared with those with moderate or low nutritional risk (P<0.01). CONCLUSIONS:
      Moderate or high nutritional risk is seen in children hospitalized in the
      surgical department. Nutritional risk score is correlated with clinical outcome.
      Nutritional support for these children is not yet properly provided. Nutritional
      risk screening and standard nutritional support should be widely applied among
      hospitalized children.

PMID- 24131843
TI  - [Clinical features and treatment of acute clenbuterol poisoning in children].
AB  - OBJECTIVE: To study clinical features, treatment and curative effects in children
      with acute clenbuterol poisoning, in order to provide a basis for early diagnosis
      and treatment. METHODS: Clinical data of 28 hospitalized children with acute
      clenbuterol poisoning in April 2011 were retrospectively studied. RESULTS: Of the
      28 patients, there were 15 males and 13 females, aged 1 to 13 years (mean age
      6.5+/-4.8 years). Vomiting, palpitations and limb shaking were found as main
      clinical manifestations in the patients. Main changes of blood biochemical
      included hypokalemia, lactic acidosis, hyperglycemia, hypsocreatinkinase. Snus
      tachycardia and S-T segment depression were observed on ECG. Patients' symptoms
      were gradually alleviated after 12-78 hours by use of beta blockers, potassium
      supplement, protecting the heart and other symptomatic and supportive treatment.
      Blood biochemical indexes were improved after 48 hours of admission. All of the
      patients were cured after 5 days. The symptoms of the patients do not longer
      occur during a follow up of half a month. CONCLUSIONS: Acute clenbuterol
      poisoning is characterized by vomiting, palpitations, limb shaking, hypokalemia,
      lactic acidosis and tachycardia in children. An early effective treatment of this
      disease can improve prognosis in children.

PMID- 24131844
TI  - [Effects of erythropoietin on cardiomyocyte apoptosis and endoplasmic reticulum
      stress-related proteins in neonatal rats with asphyxia].
AB  - OBJECTIVE: To study the effects of erythropoietin (EPO) on cardiomyocyte
      apoptosis and endoplasmic reticulum stress (ERS)-related proteins, glucose
      regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in neonatal
      rats with asphyxia. METHODS: A total of 120 newborn Sprague-Dawley rats (7 days
      old) were randomly divided into sham-operated (n=40), asphyxia (n=40) and EPO
      treated asphyxia groups (n=40). A neonatal rat model of normobaric asphyxia was
      established in the asphyxia and EPO-treated asphyxia groups. The rats in the EPO
      treated asphyxia group received intraperitoneal injection of recombinant human
      erythropoietin (500 U/mL) immediately after the model was established, while the
      other two groups received the same volume of normal saline (0.9%). Heart blood
      and myocardial tissue samples were collected from 8 rats in each group at 2, 6,
      12, 24 or 48 hours after the model was established. Serum creatine kinase (CK)
      and lactate dehydrogenase (LDH) levels were measured; cardiomyocyte apoptosis was
      evaluated, and expression of myocardial GRP78 and CHOP was measured. RESULTS:
      Compared with the sham-operated and EPO-treated asphyxia groups, the asphyxia
      group had significantly increased serum CK and LDH levels, number of apoptotic
      cells, and expression of myocardial GRP78 and CHOP at each time point (P<0.01),
      and all the indices were significantly higher in the EPO-treated asphyxia group
      than in the sham-operated group (P<0.01). At 24 hours after asphyxia, the
      expression of myocardial CHOP was positively correlated with the myocardial
      apoptosis index (r=0.944, P<0.01). CONCLUSIONS: EPO exerts a protective effect on
      the myocardium of neonatal rats with hypoxic-ischemic injury by regulating ERS
      related proteins GRP78 and CHOP and reducing cardiomyocyte apoptosis.

PMID- 24131845
TI  - [Roles of cardiac mast cells and Toll-like receptor 4 in viral myocarditis among
      mice].
AB  - OBJECTIVE: To investigate the role and significance of cardiac mast cells and
      Toll-like receptor 4 (TLR4) in the development and progression of viral
      myocarditis (VMC). METHODS: Forty-eight Balb/c mice were randomly divided into a
      control group (n=24) and a model group (n=24). Coxsackievirus B3 was
      intraperitoneally injected into the model group mice to establish a VMC model. In
      each group, cardiac tissues were collected from 8 mice at 7, 14 and 28 days after
      the model was established. The cardiac tissues were stained with hematoxylin and
      eosin as well as Masson trichrome to observe pathological changes in cardiac
      tissues. The number and degranulation of cardiac mast cells at each time point
      were measured and evaluated by toluidine blue staining and transmission electron
      microscopy. The mRNA and protein expression of TLR4 in cardiac tissues was
      measured by RT-PCR and immunohistochemistry. In the model group, the correlation
      between number of cardiac mast cells and mRNA expression of TLR4 at all time
      points was analyzed. RESULTS: The model group had significantly higher
      pathological scores of cardiac tissues than the control group at all time points
      (P<0.05). The myocardial collagen volume fraction in the model group at 28 days
      was significantly higher than in the control group at all time points and higher
      than in the model group at 7 and 14 days (P<0.05). At each time point, the model
      group had a significantly increased number of mast cells (P<0.05), and
      significantly increased mRNA and protein expression of TLR4 (P<0.05) compared
      with the control group. In the model group, the number of cardiac mast cells was
      positively correlated with the mRNA expression of TLR4 at all time points
      (R<suP>2</suP>=0.877, P<0.05). CONCLUSIONS: Mice with VMC have significantly
      increased numbers of cardiac mast cells and expression of TLR4 compared with
      control mice at all time points, suggesting that mast cells and TLR4 may play
      important roles in the inflammatory response and fibrosis of VMC.

PMID- 24131846
TI  - [Change in plasma H2S level and therapeutic effect of H2S supplementation in
      tubulointerstitial fibrosis among rats with unilateral ureteral obstruction].
AB  - OBJECTIVE: To observe the level in plasma hydrogen sulfide (H2S) and the
      expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase
      (CSE) (two key synthetases for endogenous H2S generation in the kidney) in
      obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF)
      induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S
      in TIF. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into
      sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF
      was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low
      dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and
      7.0 MUmol/kg respectively) twice daily immediately after operation, and the sham
      operated and model groups were intraperitoneally injected with an identical
      volume of normal saline. In each group, 8 rats were randomly selected and
      sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was
      measured by deproteinization. The obstructed kidney tissue was subjected to
      hematoxylin and eosin staining and Masson staining, and the renal
      tubulointerstitial injury was evaluated under a microscope. mRNA and protein
      expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR
      and immunohistochemistry respectively. RESULTS: The degree of UUO-induced renal
      tubulointerstitial injury was negatively correlated with plasma H2S concentration
      in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury
      was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the
      kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of
      TIF was reduced (P<0.01). There were no significant differences in plasma H2S
      level and mRNA and protein expression of CBS and CSE between the low-dose and
      high-dose NaHS groups (P>0.05). CONCLUSIONS: H2S is involved in the development
      of UUO-induced TIF, and the CBS/H2S and CSE/H2S systems play key roles in this
      process. H2S supplementation can delay the progression of TIF.

PMID- 24131847
TI  - [Video-electroencephalographic monitoring for paroxysmal events in critically ill
      children].

PMID- 24131848
TI  - [A confirmed diagnosis of tuberculosis by CT-guided percutaneous lung biopsy in a
      2-month infant].

PMID- 24131849
TI  - [Systemic lupus erythematosus complicated by superficial angiomyxoma in a child].

PMID- 24131850
TI  - [Research progress in mild hypothermia treatment of neonatal hypoxic-ischemic
      encephalopathy].
AB  - Randomized controlled trials have demonstrated the safety and efficacy of mild
      hypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE),
      which can reduce mortality or the incidence of severe neurological sequelae. Mild
      hypothermia has been used in the neonatal intensive care unit (NICU) as a routine
      treatment method for neonatal HIE in many developed countries, and it is
      increasingly applied in some NICUs in China. However, 40%-50% of the neonates
      treated with mild hypothermia die or develop severe neurological disability.
      Thus, to achieve the best neuroprotective effect, issues such as selection of
      patients with indications for mild hypothermia, cooling method, optimal time for
      mild hypothermia, duration of mild hypothermia, optimal target temperature, and
      the safety and long-term effects of mild hypothermia combined with other
      therapies, need to be further discussed. This article reviews the latest progress
      in clinical research on these issues. 

PMID- 24131851
TI  - [Quality of life in children with short stature: an analysis using PedsQL].
AB  - OBJECTIVE: To study the differences in quality of life and psychosocial function
      between children with short stature and children with normal stature. METHODS:
      The Pediatric Quality of Life Inventory (PedsQL) was used to survey 53 children
      aged 5-18 years who were diagnosed with short stature between June 2011 and June
      2012, and their parents or guardians. Seventy-nine healthy children aged 4-17
      years were selected as the control group. RESULTS: For PedsQL Child-Self Report,
      the children with short stature had a significantly higher total score than the
      control children (25.3+/-11.2 vs 21.1+/-10.3; P<0.05), and the former had
      significantly higher scores than the latter on the following items: It is hard
      for me to walk more than one block; It is hard for me to lift something heavy; I
      hurt or ache; I worry about what will happen to me; I cannot do things that other
      kids of my age can do; It is hard to keep up when I play with other kids; It is
      hard to pay attention in class; I forget things; I have trouble keeping up with
      my schoolwork (P<0.05). For PedsQL Parent-Proxy Report, the children with short
      stature had significantly higher scores than the control children on the
      following items: troubled sleeping; paying attention in class; keeping up with
      schoolwork; forgetting things (P<0.05). There was no significant difference in
      total score, however, between the two groups (P>0.05). CONCLUSIONS: Children with
      short stature have poorer development of psychosocial function than children with
      normal stature.

PMID- 24131852
TI  - Linkage mapping and expression analysis of miRNAs and their target genes during
      fiber development in cotton.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, endogenously expressed, non-coding RNA
      molecules involved in gene transcription and expression that combine with
      specific mRNA site of target genes to inhibit protein synthesis or degrade mRNA.
      Since the first plant miRNA was reported in 2002, numerous new miRNAs and their
      targets have been discovered via high-throughput sequencing and computational
      approaches. However, the genetic variation of miRNA genes is poorly understood
      due to the lack of miRNA-specific DNA markers. RESULTS: To study the genetic
      variation and map miRNAs and their putative target genes in cotton, we designed
      specific primers based on pre-miRNAs and published putative target genes. A total
      of 83 pre-miRNA primers and 1,255 putative target gene primers were surveyed, and
      9 pre-miRNA polymorphic loci were mapped on 7 of the 26 tetraploid cotton
      chromosomes. Furthermore, 156 polymorphic loci of the target genes were mapped on
      the cotton genome. To map more miRNA loci, miRNA-based SRAP (sequence-related
      amplified polymorphism) markers were used to map an additional 54 polymorphic
      loci on the cotton genome with the exception of Chr01, Chr22, and Chr24. Finally,
      a network between miRNAs and their targets was constructed. All pre-miRNAs and 98
      putative target genes were selected for RT-PCR analysis, revealing unique
      expression patterns across different fiber development stages between the mapping
      parents. CONCLUSIONS: Our data provide an overview of miRNAs, their putative
      targets, and their network in cotton as well as comparative expression analyses
      between Gossypium hirsutum and G. barbadense. These data provide a foundation for
      understanding miRNA regulation during cotton fiber development.

PMID- 24131853
TI  - Select human milk oligosaccharides directly modulate peripheral blood mononuclear
      cells isolated from 10-d-old pigs.
AB  - Infant formulas lack the complex mixture of oligosaccharides found in human milk.
      These human milk oligosaccharides (HMO) may be pivotal to the development of the
      neonatal immune system. Few comprehensive analyses of the effects of HMO on
      immune cells from neonates have been undertaken. Herein, the direct effects of
      HMO on immune cells were analysed ex vivo. Peripheral blood mononuclear cells
      (PBMC) isolated from 10-d-old sow-reared (SR) or colostrum-deprived formula-fed
      (FF) pigs were stimulated for 72 h with single HMO, mixtures of single HMO or a
      complex mixture of HMO isolated from human milk (iHMO). T-cell phenotype,
      cytokine production and proliferation were measured by flow cytometry,
      immunoassay and [3H]thymidine incorporation, respectively. Stimulation with HMO
      had direct effects on PBMC. For instance, cells stimulated with iHMO produced
      more IL-10 than unstimulated cells, and cells stimulated with fucosylated HMO
      tended to proliferate less than unstimulated cells. Additionally, co-stimulation
      with HMO mixtures or single HMO altered PBMC responses to phytohaemagglutinin
      (PHA) or lipopolysaccharide (LPS) stimulation. Compared with PBMC stimulated with
      PHA alone, cells co-stimulated with iHMO and PHA proliferated more and had fewer
      detectable CD4+CD8+ T cells. Compared with PBMC stimulated by LPS alone, cells co
      stimulated with a mixture of sialylated HMO and LPS proliferated more and tended
      to have fewer detectable CD4+ T cells. Differences in the baseline responses of
      PBMC isolated from the SR or FF pigs were observed. In summary, HMO directly
      affected PBMC populations and functions. Additionally, ex vivo measurements of
      PBMC phenotype, cytokine production and proliferation were influenced by the
      neonate's diet.

PMID- 24131854
TI  - Neuroethics, confidentiality, and a cultural imperative in early onset Alzheimer
      disease: a case study with a First Nation population.
AB  - The meaningful consideration of cultural practices, values and beliefs is a
      necessary component in the effective translation of advancements in neuroscience
      to clinical practice and public discourse. Society's immense investment in
      biomedical science and technology, in conjunction with an increasingly diverse
      socio-cultural landscape, necessitates the study of how potential discoveries in
      neurodegenerative diseases such as Alzheimer disease are perceived and utilized
      across cultures. Building on the work of neuroscientists, ethicists and
      philosophers, we argue that the growing field of neuroethics provides a pragmatic
      and constructive pathway to guide advancements in neuroscience in a manner that
      is culturally nuanced and relevant. Here we review a case study of one issue in
      culturally oriented neuroscience research where it is evident that traditional
      research ethics must be broadened and the values and needs of diverse populations
      considered for meaningful and relevant research practices. A global approach to
      neuroethics has the potential to furnish critical engagement with cultural
      considerations of advancements in neuroscience. 

PMID- 24131855
TI  - Stress-dose hydrocortisone reduces critical illness-related corticosteroid
      insufficiency associated with severe traumatic brain injury in rats.
AB  - INTRODUCTION: The spectrum of critical illness-related corticosteroid
      insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined
      and no effective treatments for TBI-induced CIRCI are available to date. Despite
      growing interest in the use of stress-dose hydrocortisone as a potential therapy
      for CIRCI, there remains a paucity of data regarding its benefits following
      severe TBI. This study was designed to investigate the effects of stress-dose
      hydrocortisone on CIRCI development and neurological outcomes in a rat model of
      severe traumatic brain injury. METHODS: Rats were subjected to lateral fluid
      percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either
      a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and
      0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5
      mg/kg on day 6, and 0.25 mg on day 7) or control saline solution
      intraperitoneally daily for 7 days after injury. RESULTS: We investigated the
      effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological
      deficits using an electrical stimulation test to assess corticosteroid response
      and modified neurological severity score (mNSS). We also studied pathological
      changes in the hypothalamus, especially in the paraventricular nuclei (PVN),
      after stress-dose HC or a low dose of MP was administered, including apoptosis
      detected by a TUNEL assay, blood-brain barrier (BBB) permeability assessed by
      brain water content and Evans Blue extravasation into the cerebral parenchyma,
      and BBB integrity evaluated by CD31 and claudin-5 expression. We made the
      following observations. First, 70% injured rats developed CIRCI, with a peak
      incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated
      with an increased mortality and delayed neurological recovery. Second, post
      injury administration of stress-dose HC, but not MP or saline increased
      corticosteroid response, prevented CIRCI, reduced mortality, and improved
      neurological function during the first 14 days post injury dosing. Thirdly, these
      beneficial effects were closely related to improved vascular function by the
      preservation of tight junctions in surviving endothelial cells, and reduced
      neural apoptosis in the PVN of hypothalamus. CONCLUSIONS: Our findings indicate
      that post-injury administration of stress-dose HC, but not MP reduces CIRCI and
      improves neurological recovery. These improvements are associated with reducing
      the damage to the tight junction of vascular endothelial cells and blocking
      neuronal apoptosis in the PVN of the hypothalamus.

PMID- 24131856
TI  - Effects of a bacteria-based probiotic on subpopulations of peripheral leukocytes
      and their cytokine mRNA expression in calves.
AB  - Eight Holstein calves (10 +/- 3 weeks) were used to examine the interaction
      between a bacteria-based probiotic agent (probiotic) and the function of
      peripheral blood mononuclear cells (PBMCs). The probiotic, consisting of
      Lactobacillus plantarum, Enterococcus faecium and Clostridium butyricum, was
      administered orally at 3.0 g/100 kg body weight to calves once daily for 5
      consecutive days. Calves given the vehicle alone with no probiotic served as the
      control. In the treatment group, increases in numbers of CD282(+) (TLR2)
      monocytes, CD3(+) T cells and CD4(+), CD8(+) and WC1(+) gammadelta T cell subsets
      were noted on day 7 post-placement compared to predose day and the control group.
      Expression of interleukin (IL)-6, interferon-gamma (INF-gamma) and tumor necrosis
      factor-alpha (TNF-alpha) was elevated in peripheral leukocytes on days 7 and 14.
      These results suggest that peripheral blood leukocytes in healthy calves may be
      stimulated via the gastrointestinal microbiota, which was increased by the oral
      probiotic treatment, with overall stability of the rumen bacterial flora. The 5
      day repeated administration of a bacteria-based probiotic may enhance cellular
      immune function in weaned calves.

PMID- 24131857
TI  - Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a
      general adult population: effect of gender and age: EPIRCE cross-sectional study.
AB  - BACKGROUND: Insulin resistance has been associated with metabolic and hemodynamic
      alterations and higher cardio metabolic risk. There is great variability in the
      threshold homeostasis model assessment of insulin resistance (HOMA-IR) levels to
      define insulin resistance. The purpose of this study was to describe the
      influence of age and gender in the estimation of HOMA-IR optimal cut-off values
      to identify subjects with higher cardio metabolic risk in a general adult
      population. METHODS: It included 2459 adults (range 20-92 years, 58.4% women) in
      a random Spanish population sample. As an accurate indicator of cardio metabolic
      risk, Metabolic Syndrome (MetS), both by International Diabetes Federation
      criteria and by Adult Treatment Panel III criteria, were used. The effect of age
      was analyzed in individuals with and without diabetes mellitus separately. ROC
      regression methodology was used to evaluate the effect of age on HOMA-IR
      performance in classifying cardio metabolic risk. RESULTS: In Spanish population
      the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to
      2.05 taking into account of MetS components. In non-diabetic women, but no in
      men, we found a significant non-linear effect of age on the accuracy of HOMA-IR.
      In non-diabetic men, the cut-off values were 1.85. All values are between 70th
      75th percentiles of HOMA-IR levels in adult Spanish population. CONCLUSIONS: The
      consideration of the cardio metabolic risk to establish the cut-off points of
      HOMA-IR, to define insulin resistance instead of using a percentile of the
      population distribution, would increase its clinical utility in identifying those
      patients in whom the presence of multiple metabolic risk factors imparts an
      increased metabolic and cardiovascular risk. The threshold levels must be
      modified by age in non-diabetic women.

PMID- 24131858
TI  - Vitamin D deficiency and low bone mineral density in native Chinese rheumatoid
      arthritis patients.
AB  - OBJECTIVE: We aimed to examine the risk factors related to the development of
      osteoporosis in rheumatoid arthritis (RA) patients and whether there is an
      association among the changes in bone mineral density (BMD), disease activities
      (modified DAS28), serum 25-hydroxyvitamin D (25OHD) levels, and disease duration.
      METHODS: There were 110 patients with RA and 110 age- and sex-matched healthy
      controls who were concurrently studied. All of the patients underwent the
      following measurements: erythrocyte sedimentation rate, C-reactive protein,
      rheumatoid factor, and serum 25OHD. Dual-energy X-ray absorptiometry (DEXA) was
      also used to measure the BMD of the left femur at the time of recruitment.
      Patients taking vitamin D supplement or corticosteroids were excluded. RESULTS:
      The incidences of osteopenia (45.6% vs. 36.4%, P = 0.170) and osteoporosis (33.6%
      vs. 5.45%, P = 0.000) were higher in the RA patients than in the healthy
      controls. There was a significant negative correlation between vitamin D levels
      and DAS28 (r = -0.325, P = 0.001) and a significant positive correlation between
      vitamin D levels and BMD (r = 0.422, P = 0.000). The multiple regression analysis
      revealed that 25OHD levels were significantly correlated with disease activity
      and BMD (F = 11.087, P = 0.000). Stepwise multiple regression analysis showed
      that serum 25OHD levels were the significant predictors for low BMD and high
      disease activity (DAS28) in RA patients. CONCLUSION: The incidences of
      osteoporosis and osteopenia were higher in RA patients compared to the age- and
      gender-matched healthy controls. Low serum 25OHD levels correlate with low BMD
      and high disease activity in RA patients.

PMID- 24131859
TI  - Outcomes of artificial urinary sphincter implantation in the irradiated patient.
AB  - OBJECTIVES: To present the outcomes of men undergoing artificial urinary
      sphincter (AUS) implantation. To determine the impact a history of radiation
      therapy has on the outcomes of prosthetic surgery for stress urinary
      incontinence. PATIENTS AND METHODS: A cohort of 77 consecutive men undergoing AUS
      implantation for stress urinary incontinence after prostate cancer surgery,
      including 29 who had also been irradiated, were included in a prospective
      database and followed up for a mean period of 21.2 months. Continence rates and
      incidence of complications, revision and cuff erosion were evaluated, with
      results in irradiated men compared with those of men who had undergone radical
      prostatectomy alone. The effect of co-existing hypertension, diabetes mellitus
      and surgical approach on outcomes were also examined. RESULTS: Overall, the rate
      of social continence (0-1 pad/day) was 87% and similar in irradiated and non
      irradiated men (86.2 vs 87.5%). Likewise, the incidence of infection (3.4 vs 0%),
      erosion (3.4 vs 2.0%) and revision surgery (10.3 vs 12.5%) were not significantly
      different between the groups. There was a far greater incidence of co-existing
      urethral stricture disease in irradiated patients (62.1 vs 10.4%) which often
      complicated management; however, AUS implantation was still feasible in these men
      and, in four such cases, a transcorporal cuff placement was used. There were
      poorer outcomes in patients with diabetes, and a greater re-operation rate in
      those men who underwent a transverse scrotal rather than perineal surgical
      approach, although the differences did not reach statistical significance.
      CONCLUSIONS: Previous irradiation in patients may increase the complexity of
      treatment because of a greater incidence of co-existing urethral stricture
      disease; however, these patients are still able to achieve a level of social
      continence similar to that of non-irradiated patients, with no discernable
      increase in complication rates, cuff erosion or the need for revision surgery.
      AUS implantation remains the 'gold standard' for management of moderate-to-severe
      stress urinary incontinence in both irradiated and non-irradiated patients after
      prostate cancer treatment.

PMID- 24131860
TI  - The challenges of treating anorexia nervosa.

PMID- 24131861
TI  - Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment
      as usual in outpatients with anorexia nervosa (ANTOP study): randomised
      controlled trial.
AB  - BACKGROUND: Psychotherapy is the treatment of choice for patients with anorexia
      nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of
      OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual
      based outpatient treatments for anorexia nervosa--focal psychodynamic therapy and
      enhanced cognitive behaviour therapy--versus optimised treatment as usual.
      METHODS: The ANTOP study is a multicentre, randomised controlled efficacy trial
      in adults with anorexia nervosa. We recruited patients from ten university
      hospitals in Germany. Participants were randomly allocated to 10 months of
      treatment with either focal psychodynamic therapy, enhanced cognitive behaviour
      therapy, or optimised treatment as usual (including outpatient psychotherapy and
      structured care from a family doctor). The primary outcome was weight gain,
      measured as increased body-mass index (BMI) at the end of treatment. A key
      secondary outcome was rate of recovery (based on a combination of weight gain and
      eating disorder-specific psychopathology). Analysis was by intention to treat.
      This trial is registered at http://isrctn.org, number ISRCTN72809357. FINDINGS:
      Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal
      psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to
      optimised treatment as usual. At the end of treatment, 54 patients (22%) were
      lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out.
      At the end of treatment, BMI had increased in all study groups (focal
      psychodynamic therapy 0.73 kg/m(2), enhanced cognitive behaviour therapy 0.93
      kg/m(2), optimised treatment as usual 0.69 kg/m(2)); no differences were noted
      between groups (mean difference between focal psychodynamic therapy and enhanced
      cognitive behaviour therapy -0.45, 95% CI -0.96 to 0.07; focal psychodynamic
      therapy vs optimised treatment as usual -0.14, -0.68 to 0.39; enhanced cognitive
      behaviour therapy vs optimised treatment as usual -0.30, -0.22 to 0.83). At 12
      month follow-up, the mean gain in BMI had risen further (1.64 kg/m(2), 1.30
      kg/m(2), and 1.22 kg/m(2), respectively), but no differences between groups were
      recorded (0.10, -0.56 to 0.76; 0.25, -0.45 to 0.95; 0.15, -0.54 to 0.83,
      respectively). No serious adverse events attributable to weight loss or trial
      participation were recorded. INTERPRETATION: Optimised treatment as usual,
      combining psychotherapy and structured care from a family doctor, should be
      regarded as solid baseline treatment for adult outpatients with anorexia nervosa.
      Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month
      follow-up, and enhanced cognitive behaviour therapy was more effective with
      respect to speed of weight gain and improvements in eating disorder
      psychopathology. Long-term outcome data will be helpful to further adapt and
      improve these novel manual-based treatment approaches. FUNDING: German Federal
      Ministry of Education and Research (Bundesministerium fur Bildung und Forschung,
      BMBF), German Eating Disorders Diagnostic and Treatment Network (EDNET).

PMID- 24131862
TI  - Endoscopic nasobiliary drainage with sphincterotomy in acute obstructive
      cholangitis: a prospective randomized controlled trial.
AB  - OBJECTIVE: We aimed to determine the efficacy and safety of endoscopic
      nasobiliary drainage (ENBD) with or without endoscopic sphincterotomy (EST) for
      temporary biliary decompression in patients with acute obstructive cholangitis.
      METHODS: In total, 72 patients with acute obstructive cholangitis were
      prospectively randomized to undergo emergency ENBD with EST (EST group, n = 36)
      or without EST (non-EST group, n = 36). The clinical outcomes and complications
      between the two groups were compared. RESULTS: Endoscopic nasobiliary
      decompression was successful in all 72 patients. Four patients underwent a second
      endoscopic retrograde cholangiopancreatography (ERCP) to replace the nasobiliary
      catheter due to blockage (one in the EST group and two in the non-EST group) or
      migration (one in the EST group). The mean serum gamma-glutamyltransferase and
      total bilirubin levels after treatment were significantly higher in the non-EST
      group than in the EST group (P < 0.05). However, no significant differences were
      observed for other parameters evaluated. The total complication rate was similar
      between the two groups (EST 25.0% vs non-EST 19.4%). Although hemorrhage occurred
      more frequently in the EST group and acute pancreatitis in the non-EST group,
      these differences were not significant. CONCLUSIONS: EST is helpful and safe for
      biliary drainage while ENBD without EST is the first choice for acute
      cholangitis. EST may increase the efficacy of ENBD in patients with papillary
      inflammatory stricture and thick bile.

PMID- 24131863
TI  - Methylation profiling of SOCS1, SOCS2, SOCS3, CISH and SHP1 in Philadelphia
      negative myeloproliferative neoplasm.
AB  - Janus kinase-signal transducer and activator of transcription (JAK/STAT)
      signalling, pivotal in Philadelphia-negative (Ph-ve) myeloproliferative neoplasm
      (MPN), is negatively regulated by molecules including SOCSs, CISH and SHP1.
      SOCS1, SOCS2 and SOCS3 methylation have been studied in MPN with discordant
      results. Herein, we studied the methylation status of SOCS1, SOCS2 and SOCS3,
      CISH and SHP1 by methylation-specific polymerase chain reaction (MSP) in cell
      lines and 45 diagnostic marrow samples of Ph-ve MPN. Moreover, we attempted to
      explain the discordance of methylation frequency by mapping the studied MSP
      primers to the respective genes. Methylation was detected in normal controls
      using SOCS2 MSP primers in the 3'translated exonic sequence, but not primers
      around the transcription start site in the 5' untranslated regions (5'UTR).
      SOCS1, SOCS2, SOCS3 and CISH were completely unmethylated in primary MPN samples
      and cell lines. In contrast, methylation of SHP1 was detected in 8.9% primary
      marrow samples. Moreover, SHP1 was completely methylated in K562 cell line,
      leading to reversible SHP1 silencing. A review of methylation studies of SOCS1
      and SOCS3 showed that spuriously high rates of SOCS methylation had been reported
      using MSP primers targeting CpG sites in the 3'translated exonic sequence, which
      is also methylated in normal controls. However, using MSP primers localized to
      the 5'UTR, methylation of SOCS1, SOCS2 and SOCS3 is infrequent across all
      studies. In summary, methylation of SOCS1, SOCS2, SOCS3 and CISH is infrequent in
      Ph-ve MPN. Appropriate MSP primers are important for accurate estimation of the
      methylation frequency. The role of SHP1 methylation in the pathogenesis of MPN
      warrants further investigation. 

PMID- 24131864
TI  - The demonstration of a theory-based approach to the design of localized patient
      safety interventions.
AB  - BACKGROUND: There is evidence of unsafe care in healthcare systems globally.
      Interventions to implement recommended practice often have modest and variable
      effects. Ideally, selecting and adapting interventions according to local
      contexts should enhance effects. However, the means by which this can happen is
      seldom systematic, based on theory, or made transparent. This work aimed to
      demonstrate the applicability, feasibility, and acceptability of a theoretical
      domains framework implementation (TDFI) approach for co-designing patient safety
      interventions. METHODS: We worked with three hospitals to support the
      implementation of evidence-based guidance to reduce the risk of feeding into
      misplaced nasogastric feeding tubes. Our stepped process, informed by the TDF and
      key principles from implementation literature, entailed: involving stakeholders;
      identifying target behaviors; identifying local factors (barriers and levers)
      affecting behavior change using a TDF-based questionnaire; working with
      stakeholders to generate specific local strategies to address key barriers; and
      supporting stakeholders to implement strategies. Exit interviews and audit data
      collection were undertaken to assess the feasibility and acceptability of this
      approach. RESULTS: Following audit and discussion, implementation teams for each
      Trust identified the process of checking the positioning of nasogastric tubes
      prior to feeding as the key behavior to target. Questionnaire results indicated
      differences in key barriers between organizations. Focus groups generated
      innovative, generalizable, and adaptable strategies for overcoming barriers, such
      as awareness events, screensavers, equipment modifications, and interactive
      learning resources. Exit interviews identified themes relating to the benefits,
      challenges, and sustainability of this approach. Time trend audit data were
      collected for 301 patients over an 18-month period for one Trust, suggesting
      clinically significant improved use of pH and documentation of practice following
      the intervention. CONCLUSIONS: The TDF is a feasible and acceptable framework to
      guide the implementation of patient safety interventions. The stepped TDFI
      approach engages healthcare professionals and facilitates contextualization in
      identifying the target behavior, eliciting local barriers, and selecting
      strategies to address those barriers. This approach may be of use to
      implementation teams and policy makers, although our promising findings confirm
      the need for a more rigorous evaluation; a balanced block evaluation is currently
      underway.

PMID- 24131865
TI  - Characterization of CD4+ T-cell immune activation and interleukin 10 levels among
      HIV, hepatitis C virus, and HIV/HCV-coinfected patients.
AB  - BACKGROUND: HIV/hepatitis C virus (HCV)-coinfected patients have accelerated
      liver disease compared with HCV monoinfection. In HIV-positive patients with
      viral suppression, data comparing inflammatory cytokines and immune activation
      between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV
      seropositive patients with cleared HCV are limited. METHODS: Fifty-nine age- and
      sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV
      monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and
      (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had
      undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver
      fibrosis was assessed in each subject using transient elastography. Cells were
      collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow
      cytometry and plasma for luminex-multiplex cytokine assays. RESULTS: CD38+HLA-DR+
      expression on CD4+ T cells was significantly increased in HIV/HCV coinfection
      with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4+ total HLA-DR+
      expression was significantly increased in HIV/HCV coinfection with CHC (43%)
      versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared
      HCV (38%) (P = 0.046). Total CD4+CD38+ and CD4+CD38+HLA-DR- expression was
      significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection
      (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were
      significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P =
      0.0002). In multivariate analysis, severe fibrosis was associated with lower
      expression of CD4+CD38+HLA-DR+ and CD4+ total CD38+ than mild-moderate fibrosis
      (P = 0.03 and 0.03, respectively). CONCLUSIONS: CD4 immune activation with HLA
      DR+ expression in HIV/HCV coinfection with well-controlled HIV may arise from
      chronic HCV viremia. Conversely, CD4+CD38+ expression may be driven by underlying
      HIV infection. CD4 immune activation was unexpectedly found to be associated with
      decreased liver fibrosis.

PMID- 24131866
TI  - Spontaneous thoracic spinal subarachnoid hemorrhage diagnosed with brain computed
      tomography.
AB  - Spontaneous thoracic spinal subarachnoid hemorrhage is rare, and thus no useful
      radiological findings for preoperative diagnosis have been reported. We
      experienced a patient with spontaneous thoracic spinal subarachnoid hemorrhage. A
      37-year-old female presented with sudden-onset paraplegia and numbness in the
      trunk and bilateral lower extremities. The patient had no past history of trauma,
      lumbar puncture and bleeding disorder. T2-weighted sagittal magnetic resonance
      imaging (MRI) of the cervical and thoracic spines showed a mass occupied in the
      ventral space of spinal cord that was dorsally shifted. The mass extended from C6
      to Th6 levels, with its largest size at Th2 level. Thoracic spine T2-weighted
      sagittal and axial MRI showed that the mass compressed spinal cord and was
      located in the intradural space. There was no spinal cord tumor and no spinal
      vascular malformation around the mass. Brain computed tomography (CT) showed a
      high-density area in the subarachnoid space, indicating the possibility of
      subarachnoid hemorrhage. Brain MRI showed no ruptured aneurysm. The patient was
      diagnosed as a spontaneous thoracic spinal subarachnoid hemorrhage and emergency
      surgery was selected. We performed right-side hemilaminectomy at Th1-Th6 and
      opened dura mater and arachnoid membrane. Hematoma was found in the ventral space
      of spinal cord and was removed. One year after surgery, numbness in the trunk and
      bilateral lower extremities had disappeared but paraplegia remained unchanged.
      Thoracic spine T2-weighted MRI confirmed no hematoma but showed a newly formed
      intradural cyst. Preoperative combination of brain CT and thoracic MRI is useful
      to diagnose thoracic spinal subarachnoid hemorrhage. 

PMID- 24131867
TI  - Comparison of cold crystalloid and colloid infusions for induction of therapeutic
      hypothermia in a porcine model of cardiac arrest.
AB  - INTRODUCTION: Large-volume cold intravenous infusion of crystalloids has been
      used for induction of therapeutic hypothermia after cardiac arrest. However, the
      effectiveness of cold colloids has not been evaluated. Therefore, we performed an
      experimental study to investigate the cooling effect of cold normal saline
      compared to colloid solution in a porcine model of ventricular fibrillation.
      METHODS: Ventricular fibrillation was induced for 15 minutes in 22 anesthetized
      domestic pigs. After spontaneous circulation was restored, the animals were
      randomized to receive either 45 ml/kg of 1 degrees C cold normal saline (Group A,
      9 animals); or 45 ml/kg of 1 degrees C cold colloid solution (Voluven, 6%
      hydroxyethyl starch 130/0.4 in 0.9% NaCl) during 20 minutes (Group B, 9 animals);
      or to undergo no cooling intervention (Group C, 4 animals). Then, the animals
      were observed for 90 minutes. Cerebral, rectal, intramuscular, pulmonary artery,
      and subcutaneous fat body temperatures (BT) were recorded. In the mechanical ex
      vivo sub study we added a same amount of cold normal saline or colloid into the
      bath of normal saline and calculated the area under the curve (AUC) for induced
      temperature changes. RESULTS: Animals treated with cold fluids achieved a
      significant decrease of BT at all measurement sites, whereas there was a
      consistent significant spontaneous increase in group C. At the time of completion
      of infusion, greater decrease in pulmonary artery BT and cerebral BT in group A
      compared to group B was detected (-2.1 +/- 0.3 vs. -1.6 +/- 0.2 degrees C, and 
      1.7 +/- 0.4 vs. -1.1 +/- 0.3 degrees C, p < 0.05, respectively). AUC analysis of
      the decrease of cerebral BT revealed a more vigorous cooling effect in group A
      compared to group B (-91 +/- 22 vs. -68 +/- 23 degrees C/min, p = 0.046). In the
      mechanical sub study, AUC analysis of the induced temperature decrease of cooled
      solution revealed that addition of normal saline led to more intense cooling than
      colloid solution (-7155 +/- 647 vs. -5733 +/- 636 degrees C/min, p = 0.008).
      CONCLUSIONS: Intravenous infusion of cold normal saline resulted in more intense
      decrease of cerebral and pulmonary artery BT than colloid infusion in this
      porcine model of cardiac arrest. This difference is at least partially related to
      the various specific heat capacities of the coolants.

PMID- 24131868
TI  - Requirement for integrin-linked kinase in neural crest migration and
      differentiation and outflow tract morphogenesis.
AB  - BACKGROUND: Neural crest defects lead to congenital heart disease involving
      outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in
      multiple cellular processes and embryogenesis. ILK is expressed in the neural
      crest, but its role in neural crest and outflow tract morphogenesis remains
      unknown. RESULTS: We ablated ILK specifically in the neural crest using the Wnt1
      Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of
      neural crest cells in the pharyngeal arches and outflow tract and a significant
      reduction in the expression of neural cell adhesion molecule (NCAM) and
      extracellular matrix components. ILK mutant embryos exhibited an enlarged common
      arterial trunk and ventricular septal defect. Reduced smooth muscle
      differentiation, but increased ossification and neurogenesis/innervation were
      observed in ILK mutant outflow tract that may partly be due to reduced
      transforming growth factor beta2 (TGFbeta2) but increased bone morphogenetic
      protein (BMP) signaling. Consistent with these observations, microarray analysis
      of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed
      reduced expression of genes associated with muscle differentiation, but increased
      expression of genes of neurogenesis and osteogenesis. CONCLUSIONS: Our results
      demonstrate that ILK plays essential roles in neural crest and outflow tract
      development by mediating complex crosstalk between cell matrix and multiple
      signaling pathways. Changes in these pathways may collectively result in the
      unique neural crest and outflow tract phenotypes observed in ILK mutants.

PMID- 24131869
TI  - Effect of the interaction of seaweed extracts containing laminarin and fucoidan
      with zinc oxide on the growth performance, digestibility and faecal
      characteristics of growing piglets.
AB  - Seaweed extracts (SWE) rich in laminarin and fucoidan have shown promise as a
      supplement for weaned piglets. However, successful application in pig nutrition
      depends on their bioactivity in the presence of additives such as ZnO. In the
      present study, a 2 * 2 factorial experiment was carried out to investigate the
      effect of the interaction between SWE and ZnO on the growth performance,
      digestibility and faecal characteristics of 192 weaned piglets (6.5 kg). The
      piglets were penned in groups of 4 (n 12 pens). The study consisted of two phases
      after weaning: a starter diet period from the day of weaning (0 d) to 21 d and a
      transition diet period from 21 to 40 d. The dietary treatments were as follows:
      (1) control diet; (2) control diet+ZnO; (3) control diet+SWE; (4) control
      diet+ZnO+SWE. Diets containing ZnO improved the faecal consistency of the piglets
      throughout the experimental period (0-40 d). An effect of the interaction between
      ZnO and SWE on several variable was observed. The diet containing only SWE or ZnO
      improved the feed conversion efficiency of the piglets during the transition diet
      period; however, this effect was not observed when the diet containing both ZnO
      and SWE was fed. The diet containing only SWE increased the N and organic matter
      digestibility of the piglets; however, this effect was not observed in the
      presence of ZnO. An interaction between ZnO and SWE was observed, whereby the
      faecal counts of Escherichia coli were decreased when piglets were fed the diet
      containing only SWE, but not when fed the diet containing both SWE and ZnO. In
      summary, SWE and ZnO improve growth performance when given alone, but not when
      given in combination. The biological effect of SWE on selected digestibility and
      faecal characteristics was markedly different when compared with that of ZnO.

PMID- 24131870
TI  - Silicon sheets by redox assisted chemical exfoliation.
AB  - In this paper, we report the direct chemical synthesis of silicon sheets in gram
      scale quantities by chemical exfoliation of pre-processed calcium disilicide
      (CaSi2). We have used a combination of x-ray photoelectron spectroscopy,
      transmission electron microscopy and energy-dispersive x-ray spectroscopy to
      characterize the obtained silicon sheets. We found that the clean and crystalline
      silicon sheets show a two-dimensional hexagonal graphitic structure.

PMID- 24131872
TI  - Effects of physical examination and diet consultation on serum cholesterol and
      health-behavior in the Korean pilots employed in commercial airline.
AB  - An objective of this study is to search how physical examination and diet
      consultation can influence those risk factors of cardiovascular disease. The
      subjects were 326 pilots of the "B" airline company in Korea whose total
      cholesterol values were over 220 mg/dl on their regular physical examinations
      from April 2006 to December 2008. They were divided into two groups, one who had
      diet consultation (an intervention group) and a control group. The physical
      examination components used to each group were body mass index (BMI), total
      cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL)
      and triglyceride (TG). The behavioral, anthropometric and biomedical measurements
      were collected at each visit. This study compares and investigates the changes of
      serum cholesterol and also the health-behavior at each physical examination.
      Within the intervention group significant improvements were observed for total
      cholesterol, BMI (body mass index) and HDL (high density lipoprotein). The
      normalizing rates for cholesterol level to decrease down to lower than 200 mg/dl
      were 17.7% in intervention group and 8.7% in control group, which is
      statistically significantly higher among the intervention group. The odds ratio
      of diet consultation was 2.80 (95% CI=1.35-5.79), which indicates that it is a
      significantly contributing factor to normalize the serum cholesterol value down
      to lower than 200 mg/dl. Based on result, it is recommended to have regular
      physical examination and intensive management with diet and exercise
      consultation. 

PMID- 24131871
TI  - Genome analysis of Pseudoalteromonas flavipulchra JG1 reveals various survival
      advantages in marine environment.
AB  - BACKGROUND: Competition between bacteria for habitat and resources is very common
      in the natural environment and is considered to be a selective force for
      survival. Many strains of the genus Pseudoalteromonas were confirmed to produce
      bioactive compounds that provide those advantages over their competitors. In our
      previous study, P. flavipulchra JG1 was found to synthesize a Pseudoalteromonas
      flavipulchra antibacterial Protein (PfaP) with L-amino acid oxidase activity and
      five small chemical compounds, which were the main competitive agents of the
      strain. In addition, the genome of this bacterium has been previously sequenced
      as Whole Genome Shotgun project (PMID: 22740664). In this study, more extensive
      genomic analysis was performed to identify specific genes or gene clusters which
      related to its competitive feature, and further experiments were carried out to
      confirm the physiological roles of these genes when competing with other
      microorganisms in marine environment. RESULTS: The antibacterial protein PfaP may
      also participate in the biosynthesis of 6-bromoindolyl-3-acetic acid, indicating
      a synergistic effect between the antibacterial macromolecule and small molecules.
      Chitinases and quorum quenching enzymes present in P. flavipulchra, which
      coincide with great chitinase and acyl homoserine lactones degrading activities
      of strain JG1, suggest other potential mechanisms contribute to
      antibacterial/antifungal activities. Moreover, movability and rapid response
      mechanisms to phosphorus starvation and other stresses, such as antibiotic,
      oxidative and heavy metal stress, enable JG1 to adapt to deleterious, fluctuating
      and oligotrophic marine environments. CONCLUSIONS: The genome of P. flavipulchra
      JG1 exhibits significant genetic advantages against other microorganisms,
      encoding antimicrobial agents as well as abilities to adapt to various adverse
      environments. Genes involved in synthesis of various antimicrobial substances
      enriches the antagonistic mechanisms of P. flavipulchra JG1 and affords several
      admissible biocontrol procedures in aquaculture. Furthermore, JG1 also evolves a
      range of mechanisms adapting the adverse marine environment or multidrug rearing
      conditions. The analysis of the genome of P. flavipulchra JG1 provides a better
      understanding of its competitive properties and also an extensive application
      prospect.

PMID- 24131873
TI  - Association between genetic variations in GRHL2 and noise-induced hearing loss in
      Chinese high intensity noise exposed workers: a case-control analysis.
AB  - The grainyhead like 2 (GRHL2) is a transcription factor, and the role among noise
      exposed workers is not well established. We tested whether GRHL2 polymorphisms
      are associated with the risk of noise-induced hearing loss (NIHL) in Chinese high
      intensity noise exposed workers. We genotyped six polymorphisms of GRHL2 gene
      (i.e., rs611419, rs3779617, rs3735713, rs3735714, rs3735715, and rs6989650) of
      340 NIHL cases and 356 control subjects who exposed to noise higher than 85 dB
      (A) [Lex, 8 h=time-weighted average of levels of noise exposure (Lex) for a
      nominal 8 h working day] in a Chinese population. Compared with rs611419 AA
      genotype, the AT/TT genotypes conferred protection against NIHL [adjusted odds
      ratio (OR)=0.71, 95% confidence interval (CI)=0.52-0.98]. No altered NIHL risk
      was associated with the other five polymorphisms. In the combined analyses, we
      found that the combined genotypes with three to eight variant alleles were
      associated with an decrease risk of NIHL compared with those with zero to two
      variant alleles, and the decrease risk was more pronounced among subgroups of
      exposure time>20 yr (0.31, 0.16-0.62) and drinkers (0.51, 0.29-0.90).
      Polymorphisms of GRHL2 may positively contribute to the etiology of NIHL. 

PMID- 24131874
TI  - Obstructive pulmonary function impairment among Korean male workers exposed to
      organic solvents, iron oxide dust, and welding fumes.
AB  - We evaluated spirometric obstructive pulmonary function impairment among workers
      who were occupationally exposed to organic solvents, iron oxide dust, or welding
      fumes. Data were collected from records of periodic health examinations of
      workers. In total, 448 Korean male workers were enrolled and classified into
      three exposure groups: exposure to organic solvents, iron oxide dust, or welding
      fumes. Logistic regression analysis was performed to evaluate the association
      between occupational exposure and pulmonary function. Compared to exposure to
      organic solvents, exposure to iron oxide dust was significantly associated with
      obstructive pulmonary function impairment (odds ratio [OR], 9.61; 95% confidence
      interval [CI], 2.20-41.97). The group exposed to welding fumes did not show a
      significantly higher OR compare to those exposed to organic solvents (OR, 2.83;
      95% CI, 0.74-10.8). These results suggest that exposure to iron oxide dust has a
      greater association with obstructive pulmonary function impairment than exposure
      to organic solvents or welding fumes. 

PMID- 24131875
TI  - Novel frameworks for understanding pediatric obesity.

PMID- 24131876
TI  - Obesity-related behaviors of US- and non-US-born parents and children in low
      income households.
AB  - OBJECTIVE: To examine differences in obesity-related behaviors by parental US
      born status among low-income, minority families participating in Healthy Habits,
      Happy Homes, an intervention trial to improve household routines for childhood
      obesity prevention. Evidence suggests lower obesity risk among adult immigrants,
      but research is inconclusive regarding the influence of having a non-US-born
      parent on childhood obesity. METHOD: We sampled 57 US-born and 64 non-US-born
      families of children aged 2 to 5.9 years living in the Boston area. At baseline,
      parents reported their own screen time, physical activity, diet, and sleep as
      well as their children's behaviors. We used linear and logistic regression to
      examine the association of parental US-born status with obesity-related
      behaviors. RESULTS: Mean (SD) body mass index z score was 0.94 (1.16), and it did
      not differ between the groups. After adjusting for parental education and child
      race/ethnicity, children of non-US-born (vs US-born) parents had later bedtimes
      (0.81 hours later; 95% confidence interval [CI], 0.37-1.25) and wake-up times
      (0.56 hours later; 95% CI, 0.16-0.95) and engaged in less active play (0.15 fewer
      hr/d; 95% CI, -0.28 to -0.01). Non-US-born (vs US-born) parents had less screen
      exposure. CONCLUSION: In this cross-section of low-income, urban families, having
      a parent born outside the United States was associated with a profile of risk and
      protective behavior; adjustment for education and race/ethnicity removed the
      protective associations of parental nativity with child behavior. Obesity-related
      differences in behaviors and home environments should be considered when
      designing interventions targeting low-income communities with a high proportion
      of non-US-born participants.

PMID- 24131877
TI  - Social and behavioral risk factors for obesity in early childhood.
AB  - OBJECTIVE: Although multiple social and behavioral risk factors associated with
      obesity co-occur among young children, most studies have examined them
      separately. The purpose of this study was to examine the relationship between
      social risk factors, behavioral problems, health behaviors, and obesity among
      preschoolers in the Fragile Families and Child Wellbeing Study (N = 1589).
      METHODS: A cumulative social risk score was created by summing maternal reports
      of intimate partner violence, food insecurity, housing insecurity, maternal
      depressive symptoms, maternal substance use, and father's incarceration, obtained
      when the child was 3 years old. Mothers reported on the child's internalizing and
      externalizing behaviors with the Child Behavior Checklist at age 5 years. Mothers
      also reported on hours the child spent watching television and sleeping as well
      as servings of soda or juice drinks the child consumed per day. Child height and
      weight were measured at age 5 years. Obesity was defined as body mass index >=
      95th percentile. RESULTS: In regression analyses adjusted for health behaviors,
      behavioral problems, and sociodemographic factors, cumulative social risk was
      associated with obesity among girls. Externalizing behavioral problems were
      associated with obesity among girls (prevalence ratios [PRs], 1.5; 95% confidence
      interval [CI], 1.2-1.7) and boys (PR, 1.3; 95% CI, 1.1-1.6). Short sleep duration
      was also associated with obesity among girls (PR, 1.2; 95% CI, 1.0-1.4) and boys
      (PR, 1.3; 95% CI, 1.1-1.5) even after adjusting for behavioral problems and
      social risk factors. Watching more than 2 hours of television per day was
      associated with obesity among boys (PR 1.5; 95% CI, 1.2 to 1.9) but not girls.
      CONCLUSION: Co-occurring social and behavioral risk factors are associated with
      obesity among 5-year-old children.

PMID- 24131878
TI  - Emotion regulation is related to children's emotional and external eating.
AB  - OBJECTIVE: The objective of this study was to examine the associations between 2
      types of emotion regulation (reactivity and inhibition) and 2 types of non-hunger
      based eating (emotional eating and external eating). Although emotion regulation
      and eating regulation problems have both been linked to obesity in previous
      studies, there is little research examining the link between the two,
      particularly among children. METHODS: A total of 782 rural second graders (49%
      girls, 20% American Indian) were followed longitudinally through third grade.
      During both data collection points, children participated in face-to-face
      interviews at school using the Children's Emotion Management Scales and the
      revised Dutch Eating Behavior Questionnaire. RESULTS: Correlational analyses
      revealed that children's emotion regulation was significantly related to both
      external and emotional eating within and across grades, with reactivity appearing
      to be more consistently related to eating regulation than was inhibition.
      Regression analyses showed that second to third grade increases in external and
      emotional eating were predicted by increases in reactivity to anger and
      reactivity to worry. CONCLUSIONS: Given the established link in previous research
      between poor behavioral regulation and obesity in children, findings from this
      study linking child emotional reactivity and emotional and external eating (both
      forms of behavior dysregulation) are important in informing prevention and
      treatment programs. Based on these findings, targeting child emotion regulation
      in addition to behavior regulation skills as part of prevention and intervention
      programs may improve program effectiveness.

PMID- 24131879
TI  - ADHD is a risk factor for overweight and obesity in children.
AB  - OBJECTIVE: Although hyperactivity would seem to increase energy expenditure,
      attention-deficit hyperactivity disorder (ADHD) appears to increase the risk for
      being overweight. This study examined the body mass index (BMI) in children with
      ADHD and its relationship with age, gender, ADHD and comorbid symptom severity,
      inhibitory control, developmental coordination disorder, sleep duration, and
      methylphenidate use. METHOD: Participants were 372 Dutch children with ADHD
      combined type aged 5 to 17 years participating in the International Multicenter
      ADHD Genetics (IMAGE) study. We categorized BMI according to international age-
      and gender-specific reference values and calculated BMI-standard deviation scores
      (BMI-SDS). The control population was matched for age, gender, and ethnicity and
      originated from the same birth cohort as the ADHD group. Inhibitory control was
      measured by the computerized Stop-signal task. Prevalence differences of
      underweight, overweight, and obesity between groups were expressed in odds
      ratios. We used linear regression analyses with gender, age, parent- and teacher
      rated ADHD and comorbid scores, inhibitory control, sleep duration, motor
      coordination, and methylphenidate use to predict BMI-SDS. RESULTS: Boys with ADHD
      aged 10 to 17 years and girls aged 10 to 12 years were more likely to be
      overweight than children in the general Dutch population. Younger girls and
      female teenagers, however, seemed to be at lower risk for being overweight.
      Higher oppositional behavior and social communication problems related to higher
      BMI-SDS scores, whereas more stereotyped behaviors related to lower BMI-SDS
      scores. We found no effects of the other examined associated risk factors on BMI
      SDS. CONCLUSIONS: Attention-deficit hyperactivity disorder in boys is a risk
      factor for overweight. In girls with ADHD, the prevalence of overweight is age
      dependent and most pronounced in girls aged 10 to 12 years. They have a 4-fold
      risk of being obese. Higher oppositional and social communication problems pose
      an increased risk for overweight, whereas sleep duration, motor coordination
      problems, and methylphenidate use do not.

PMID- 24131880
TI  - Predicting health-related quality of life from the psychosocial profiles of youth
      seeking treatment for obesity.
AB  - OBJECTIVE: To identify, in a sample of youth seeking treatment for obesity,
      subgroups of youth characterized by distinct profiles of psychosocial functioning
      and to examine whether psychosocial subgroup membership predicted treatment
      outcomes. METHODS: Baseline psychosocial profiles identified using cluster
      analysis techniques were used to predict treatment outcomes (i.e., health-related
      quality of life, BMI z scores). Participants were 92 youths seeking treatment for
      obesity (mean age = 11.6 years, mean body mass index for age and sex = 30.5) and
      their caregivers. RESULTS: Three distinct psychosocial profile subgroups were
      identified. Subgroups with higher levels of psychosocial problems had poorer
      health-related quality of life outcomes posttreatment and at 12-month follow-up.
      Subgroup membership did not predict weight outcomes. CONCLUSION: Youth seeking
      weight management treatment may present with patterns of psychosocial
      difficulties with implications for treatment outcomes. Weight treatment
      interventions should be tailored to meet the needs of youth with higher levels of
      psychosocial problems.

PMID- 24131881
TI  - Parental alliance and family functioning in pediatric obesity from both parents'
      perspectives.
AB  - OBJECTIVE: The aim of the present study was to investigate the maternal and
      paternal specific contributions on the associations between family socioeconomic
      status, parental anthropometric factors, parental alliance, and family
      functioning. These were assessed separately for mothers and fathers, by means of
      a case-control study with families of Italian youths with and without
      overweight/obesity. METHODS: Ninety families with children aged 11 to 16 years
      (mean = 13.27 years; SD = 1.5) participated in the study. Half of the families
      included children with overweight/obesity (n = 45). The body mass indices (BMIs)
      of youths and parents were measured and the former transformed in BMI z-scores.
      The parents completed the Parenting Alliance Measure and the Family Assessment
      Measure Version III, General Scale. RESULTS: Higher levels of dysfunction in
      parental alliance and family functioning of the mothers and fathers of the
      overweight/obese group were found. Socioeconomic status did not contribute
      significantly to the prediction of overweight and obesity in youth. Both maternal
      and paternal BMIs were positively associated with youth overweight/obesity. The
      degrees of parental alliance perceived by both mothers (odds ratio [OR], 81; 95%
      confidence interval [CI], 0.72-0.90) and fathers (OR, 89; 95% CI, 0.81-0.98)
      predicted child's weight status. The perception of poor parental and familial
      functioning by both parents contributed to the prediction of overweight and
      obesity in youth (mother: OR, 1.06; 95% CI, 1.02-1.10; father: OR, 1.06; 95% CI,
      1.01-1.11). CONCLUSION: The results support a strong effect of parental and
      family functioning on a youth's overweight/obesity also from the father's
      perspective. The importance of considering the father's perspective is discussed.

PMID- 24131882
TI  - Multimethod analyses of discretionary time use and health behaviors among urban
      low-income African-American adolescents: a pilot study.
AB  - OBJECTIVE: The objective of this pilot study was to examine the relations between
      discretionary time (DT) social context, health behaviors (dietary intake and
      physical activity), and body mass index (BMI) in a sample of urban low-income
      African-American early adolescents. METHODS: Multiple methods were used,
      including accelerometers, 24-hour dietary recalls, anthropometric measurements,
      and Experience Sampling Method (ESM). Participants included 9 boys (mean = 12.9
      years) and 16 girls (mean = 12.9 years). Sixteen participants were at a healthy
      weight (10 girls and 6 boys), and 9 were overweight or obese (5 girls and 3
      boys). RESULTS: Eighth graders had higher BMI z scores, engaged in less healthful
      eating during DT, and spent less time in vigorous exercise in DT than sixth
      graders. Participants spent the majority of DT with siblings, which was
      associated with increased light physical activity as measured by accelerometers.
      The ESM data suggested that adolescents engaged in increased physical activity
      and decreased sedentary activity when with peers but increased sedentary activity
      when with parents. Increased percentage of DT spent with parents was associated
      with increased daily fat intake. Data also indicate high consumption of unhealthy
      foods across all DT social contexts and activities. CONCLUSIONS: Peers may
      provide a protective social context with regard to obesity-related health
      behaviors. Targeting changes in health behaviors during the middle school years
      may be an effective means of decreasing obesity risk among urban African-American
      adolescents. Interventions for urban African-American early adolescents may
      benefit from facilitating physical activity with peers and targeting change in
      family health behaviors.

PMID- 24131883
TI  - Provider communication behaviors that predict motivation to change in black
      adolescents with obesity.
AB  - OBJECTIVE: The goal of this research was to identify communication behaviors used
      by weight loss counselors that mostly strongly predicted black adolescents'
      motivational statements. Three types of motivational statements were of interest:
      change talk (CT; statements describing their own desires, abilities, reasons, and
      need for adhering to weight loss recommendations), commitment language (CML;
      statements about their intentions or plans for adhering), and counterchange talk
      (CCT; amotivational statements against change and commitment). METHODS: Thirty
      seven black adolescents with obesity received a single motivational interviewing
      session targeting weight-related behaviors. The video-recorded transcribed
      sessions were coded using the Minority Youth Sequential Coding for Observing
      Process Exchanges generating a sequential chain of communication. Data were then
      subjected to sequential analysis to determine causal relationships between
      counselor and adolescent communication. RESULTS: Asking open-ended questions to
      elicit adolescent CT and emphasizing adolescents' autonomy most often led to CT.
      Open-ended questions to elicit CML, reflecting adolescent CML, and emphasizing
      autonomy most often led to CML. In contrast, open-ended questions to elicit CCT,
      reflecting CCT, reflecting ambivalence, and neutral open-ended questions about
      the target behavior led to CCT. CONCLUSIONS: This study provides clinicians with
      insight into the most effective way to communicate with black adolescents with
      obesity about weight loss. Specifically, reflective statements and open questions
      focusing on their own desires, abilities, reasons, need, and commitment to weight
      loss recommendations are more likely to increase motivational statements, whereas
      other types of reflections and questions may be counterproductive. Finally,
      because adolescents have a strong need for autonomous decision making,
      emphasizing their autonomy may be particularly effective in evoking motivational
      statements.

PMID- 24131884
TI  - An in-home intervention to improve nutrition, physical activity, and knowledge
      among low-income teen mothers and their children: results from a pilot study.
AB  - OBJECTIVE: Teenage pregnancy is a major public health concern in the United
      States. In addition to other life stressors, adolescent mothers and their
      children are at risk for obesity and other negative health outcomes. The current
      study examines the impact of a brief in-home educational intervention designed to
      improve health knowledge and behavior in a sample of low-income adolescent
      mothers. METHOD: Forty-six teen mothers received 6 in-home educational sessions
      focused on nutrition and physical activity, with baseline and follow-up knowledge
      and behavior assessments. RESULTS: Results indicate significant improvements in
      mothers' health knowledge and physical activity pertaining to themselves and to
      their children, and also an unexpected increase in sedentary behaviors.
      CONCLUSION: Results from this study indicate that knowledge-focused interventions
      may be an effective method to facilitate positive health behavioral change for
      teenage mothers.

PMID- 24131885
TI  - The effects of imposed sedentary behavior and exercise on energy intake in
      adolescents with obesity.
AB  - OBJECTIVE: Exercise has been shown to decrease subsequent energy intake, without
      modification of appetite, in adolescents who are obese. This study compared the
      impact of acute exercise with imposed sedentary behaviors on the daily
      nutritional adaptations and energy balance of youths with obesity. METHODS: Body
      composition and maximal oxygen uptake were assessed in 10 12- to 15-year-old
      adolescents with obesity. Energy consumption, appetite, and energy expenditure
      were assessed during 3 experimental sessions: (1) exercise session (EX), (2) bed
      rest session (BR), and (3) control session (CON). RESULTS: Total and morning
      energy expenditures were significantly higher during EX compared to CON and BR
      sessions (p < .001), and no differences were found during the afternoon energy
      expenditure between conditions (BR: 1056.5 +/- 121.5; CON: 1185.7 +/- 173; EX:
      996.1 +/- 153.4 Kcal). Total energy intake was significantly reduced on EX (p <
      .001). Dinner energy intake was significantly reduced during EX (491.65 +/- 75.74
      Kcal) and CON (666.55 +/- 152.09 Kcal) compared with BR (818.87 +/- 122.97 Kcal)
      (p < .001). Appetite was not affected. CONCLUSION: Whereas intense exercise
      reduces daily energy balance in adolescents with obesity by mainly affecting ad
      libitum dinner energy consumption, imposed sedentary behaviors lead to increased
      energy intake and then positive energy balance. The impact of exercise or imposed
      sedentary behaviors on the energy balance of adolescents with obesity is not only
      related to the exercise-induced energy expenditure, but also to their energy
      intake.

PMID- 24131886
TI  - Bullying and ADHD: which came first and does it matter?
AB  - CASE: Aiden, a 13-year-old boy in the sixth grade who is relatively new to your
      practice, is seen for follow-up after his routine physical last month when you
      noted concerns for possible attention-deficit hyperactivity disorder (ADHD) and
      gave the family Vanderbilt Scales to complete. Aiden has a family history of
      ADHD, specific learning disabilities, and mood disorder.His mother reports that
      she is concerned about how Aiden is doing at school; his teachers are complaining
      that he is not doing his work, and she is worried that he may be kept back in
      school. Aiden first began having trouble in the third grade. He was retained in
      the fourth grade for academic and behavioral reasons. Now his mother has been
      receiving calls about him not paying attention, distracting others, and staring
      at his paper. At home, he does not want to do homework and gets very frustrated.
      In fifth grade, he had a psychoeducational evaluation and was found not eligible
      for services. His achievement testing showed average scores in reading, math, and
      writing. Cognitive testing demonstrated average scores for verbal and nonverbal
      abilities and memory but was significantly below average for processing speed.
      Aiden continues to have problems now in into the sixth grade.You speak with Aiden
      in the office and ask him about school. He says, "It's bad. I'm failing." He
      believes his major problems at school are that he is not doing his homework, he
      easily becomes frustrated, and he argues with the teachers. He has supportive
      relationships with his family and friends at school. He gets along well with some
      of his teachers, noting that he loves his science teacher even though she is
      tough and "gives hard homework." He describes his history teacher as "annoying."
      When you ask what he means he states this teacher "Can be not nice and says mean
      things. She picks on me a lot." His description is consistent with the use of
      shaming as a behavior he experiences at school.You review the completed parent
      and teacher Vanderbilt forms; both are consistent and concerning for combined
      type ADHD. You discuss the diagnosis of ADHD with his mother and both agree to
      revisit pharmacotherapy in September when the school year resumes. You give her
      resources on ADHD and classroom accommodations and discuss requesting a 504 plan
      at school. You also discuss behavioral therapy to better address his self
      regulation skills.A week later, you receive a telephone call from Aiden's mother.
      "Aiden got home today and he is more upset than I have ever seen him! His teacher
      told him in front of the class that he would probably stay back a year and now he
      is saying there is no point in going to school." She is not aware if retention
      has been recommended for Aiden.What would you say to Aiden's mother? What would
      you do next?

PMID- 24131888
TI  - Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid
      leukemia.
AB  - Patients with chronic myeloid leukemia develop resistance to both first
      generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of
      mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD
      mutations that confer resistance to TKIs have been identified, and the T315I
      mutant has proven particularly difficult to target. This review summarizes the
      prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in
      patients with chronic myeloid leukemia who are treated with current TKIs and
      provides an overview of recent treatment guidelines and future trends for the
      detection of mutations. 

PMID- 24131890
TI  - Patients with prostate cancer continue to have excess mortality up to 15 years
      after diagnosis.
AB  - OBJECTIVE: To estimate the population-based conditional 5-year relative survival
      rates for patients with prostate cancer (PCa). PATIENTS AND METHODS: All 98 672
      patients, aged 45-89 years, diagnosed in the Netherlands with PCa (clinical T
      stage 1-4) in the period 1989-2008 were selected from the Netherlands Cancer
      Registry and followed up until 2010. The conditional 5-year relative survival
      rate was estimated for every subsequent year of survival up to 15 years after
      diagnosis. RESULTS: The conditional 5-year relative survival rate decreased with
      survival time from diagnosis. Excess mortality (conditional 5-year relative
      survival rate <95%) for patients with clinical T1 stage only became manifest 5
      years after diagnosis and increased to almost 10% after 10 years. Patients with
      more advanced disease (cT2-cT4) were found to have an excess mortality rate of 6
      12% at diagnosis, which increased to 15-22% after 10 years. Excess mortality
      occurred earlier for the older age groups. The 5-year relative survival rate at
      diagnosis was <90% for all age groups of patients with cT3/cT4 disease and excess
      mortality for this group increased to >20% for those who had already survived for
      5 years since diagnosis. CONCLUSIONS: Patients with PCa were found to have excess
      mortality within 10 years of diagnosis. Excess mortality was found at an earlier
      timepoint for patients with a more advanced stage and for older age groups.
      Quantitative insight into conditional survival is useful for caregivers to help
      plan optimum cancer treatment and surveillance and to inform patients about their
      actual prognosis during follow-up, taking the current condition of the patient
      into account.

PMID- 24131889
TI  - No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with
      breast cancer in Mexican women.
AB  - Breast cancer is the most frequent malignancy affecting women worldwide. It has
      been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor
      Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology
      of the disease. However, studies looking at the presence of these viruses in
      breast cancer have produced conflicting results, and this possible association
      remains controversial. Here, we used polymerase chain reaction assay to screen
      specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from
      Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were
      positive for either virus in a first round PCR and only 4 tumor samples were EBV
      positive by a more sensitive nested PCR. Considering the study's statistical
      power, these results do not support the involvement of EBV and MMTV-LV in the
      etiology of breast cancer. 

PMID- 24131891
TI  - Molecular characterization of Lys49 and Asp49 phospholipases A2from snake venom
      and their antiviral activities against Dengue virus.
AB  - We report the detailed molecular characterization of two PLA2s, Lys49 and Asp49
      isolated from Bothrops leucurus venom, and examined their effects against Dengue
      virus (DENV). The Bl-PLA2s, named BlK-PLA2 and BlD-PLA2, are composed of 121 and
      122 amino acids determined by automated sequencing of the native proteins and
      peptides produced by digestion with trypsin. They contain fourteen cysteines with
      pIs of 9.05 and 8.18 for BlK- and BlD-PLA2s, and show a high degree of sequence
      similarity to homologous snake venom PLA2s, but may display different biological
      effects. Molecular masses of 13,689.220 (Lys49) and 13,978.386 (Asp49) were
      determined by mass spectrometry. DENV causes a prevalent arboviral disease in
      humans, and no clinically approved antiviral therapy is currently available to
      treat DENV infections. The maximum non-toxic concentration of the proteins to LLC
      MK2 cells determined by MTT assay was 40 ug/mL for Bl-PLA2s (pool) and 20 ug/mL
      for each isoform. Antiviral effects of Bl-PLA2s were assessed by quantitative
      Real-Time PCR. Bl-PLA2s were able to reduce DENV-1, DENV-2, and DENV-3 serotypes
      in LLC-MK2 cells infection. Our data provide further insight into the structural
      properties and their antiviral activity against DENV, opening up possibilities
      for biotechnological applications of these Bl-PLA2s as tools of research.

PMID- 24131892
TI  - Validity of Italian version of the Child Perceptions Questionnaire (CPQ11-14).
AB  - BACKGROUND: The Child Perceptions Questionnaire (CPQ11-14) is the most commonly
      used indicator of child oral health-related quality of life (OHRQoL), and its
      validity and reliability have been studied both in English and in other
      linguistic contexts. The aim of this study was to develop a CPQ11-14 for use in
      Italy and to test its validity in a random sample of fourteen year-old Italian
      adolescents. METHODS: Once the CPQ11-14was translated into Italian and adapted
      for an Italian public, five hundred sixty-one adolescents were recruited for
      testing. Parents rated their social status; the children/adolescents were
      administered the questionnaire and underwent a dental examination during which
      their dental status was taken and recorded. Cronbach's alpha was used to assess
      the questionnaire's internal consistency. Spearman's correlation coefficients
      were calculated to assess construct validity between the total and subscale
      scores and the respondents' global ratings on oral health and well-being.
      Discriminant validity was analysed using the Kruskal-Wallis or Mann-Whitney tests
      in groups defined by gender, social position, caries experience and previous or
      no orthodontic treatment. RESULTS: The mean score on the CPQ11-14 was 15.4
      (SD=11.9), and the scores on all the domains were found to be highly skewed.
      Cronbach's alpha ranged from 0.85 to 0.90. The global ratings on oral health and
      well-being were correlated to the total score and to the sub-scores except for
      those regarding the functional limitations. There were significant differences in
      the two genders, in the groups that had already or had not yet undergone
      orthodontic treatment, and in the social classification groups, while the
      difference between those who had and those who did not have caries experience did
      not reach statistical significance. CONCLUSIONS: The Italian version of the CPQ11
      14 appears to be a reliable, valid instrument for Italian children/adolescents.

PMID- 24131893
TI  - Diagnostic and Demographic Differences Between Incarcerated and Nonincarcerated
      Youth (Ages 6-15) With ADHD in South Carolina.
AB  - OBJECTIVE: Analyze diagnostic and demographic factors to identify predictors of
      delinquency resulting in incarceration within a group of children/adolescents
      diagnosed with ADHD. METHOD: The study followed a cohort of 15,472 Medicaid
      covered children/adolescents with ADHD, ages 6 to 15 inclusive, between January
      1, 2003, and December 31, 2006. The Diagnostic and Statistical Manual of Mental
      Disorders (4th ed., text rev. [ DSM-IV-TR]), 2000 Codes were used for qualifying
      diagnosis codes. Available demographic characteristics included race, sex, and
      residence. The outcome was incarceration at the South Carolina Department of
      Juvenile Justice during 2005-2006. RESULTS: Among youth with ADHD, incarceration
      was more likely among black, male, and urban youth. Children/adolescents with
      comorbid ODD and/or CD were at greater risk compared with those with ADHD alone.
      CONCLUSION: Within ADHD-diagnosed youth, comorbid conditions and demographic
      characteristics increase the risk of incarceration. Intervention and treatment
      strategies that address behavior among youth with these characteristics are
      needed to reduce incarceration.

PMID- 24131894
TI  - Postsecondary ADHD Documentation Requirements: Common Practices in the Context of
      Clinical Issues, Legal Standards, and Empirical Findings.
AB  - OBJECTIVE: To evaluate the information postsecondary institutions require when
      determining disability service eligibility for students with reported ADHD.
      METHOD: ADHD documentation requirements of 200 U.S. institutions were surveyed by
      reviewing guidelines posted on disability services websites. RESULTS: Whereas
      virtually all institutions required documentation, findings revealed significant
      variability in requirements across institutions. Required variables most often
      included a qualified evaluator (80%), diagnostic statement (75%), and
      identification of substantial limitations (73%), but only 5 of 46 evaluated
      variables were required by at least 50% of institutions. Supportive data such as
      diagnostic criteria, standardized assessment results, and rationale for
      accommodations were rarely required. CONCLUSION: The majority of institutions
      required little to verify ADHD as a disability. Furthermore, there was little
      agreement on what components are essential for verification. When integrated with
      research, a large portion of guidelines failed to address identified weaknesses
      in ADHD diagnosis and disability determination.

PMID- 24131897
TI  - Blood pressure and neurohormonal responses to renal nerve ablation in treatment
      resistant hypertension.
AB  - OBJECTIVE: Catheter-based renal nerve ablation is a novel therapy for treatment
      resistant hypertension. Although the precise mechanism is unknown, a reduction in
      global sympathetic tone and renal sympathetic tone, potentially resulting in a
      decrease in renin, may account for the antihypertensive effect. DESIGN AND
      METHODS: In 17 patients (mean age 51.2 +/- 9.4 years) with treatment-resistant
      hypertension (antihypertensive drugs 4.7 +/- 1.3), office and ambulatory blood
      pressure (BP) measurements and circulating concentrations of catecholamines,
      renin, aldosterone and endothelin-1 were measured at baseline and 6 and 12 months
      after ablation. Office BP was measured for 1 h at 5-min intervals using an
      automatic device. RESULTS: Office BP (164.7 +/- 27.7/102.3 +/- 19.3  mmHg)
      decreased by 5.7 +/- 18.8  mmHg (P = 0.11) systolic and by 2.6 +/- 10.7 (P =
      0.33) mmHg diastolic after 6 months, whereas after 12 months decreases were 12.7
      +/- 16.0  mmHg (P = 0.007) and 7.3 +/- 11.9  mmHg (P = 0.02). Heart rate, 24-h
      (151.8 +/- 12.6/94.2 +/- 10.3  mmHg) and day and night ambulatory BP did not
      change, after either 6 or 12 months. Of the neurohormones, only plasma
      noradrenaline (397  pg/ml, interquartile range 268-461  pg/ml) decreased by 128
      +/- 167  pg/ml (P = 0.008) after 6 months, whereas other neurohormones remained
      unchanged. Forty-seven percent of patients had at least 10  mmHg decrease in 24-h
      ambulatory SBP. In these responders, office and ambulatory BP tended to be higher
      than in nonresponders, but neurohormones or changes after ablation between
      responders and nonresponders did not differ. CONCLUSION: Renal nerve ablation in
      treatment-resistant hypertensive patients had a moderate effect on office BP and
      is associated with a decrease in plasma noradrenaline but not in renin. The
      absent decrease in renin may imply that the intensity of efferent renal
      denervation achieved with the number of ablations applied was insufficient.

PMID- 24131898
TI  - Is there a change in the epidemiology of nasal fractures in females in the UK?
AB  - OBJECTIVE: To determine whether there is a change in the epidemiology of nasal
      fractures in females in the UK, and the potential contribution of the 'ladette'
      culture. METHODS: This paper reports a multi-centre retrospective study.
      Operating theatre data for all females who underwent manipulation of nasal
      fractures under anaesthesia between 2002 and 2009 were analysed. In addition, the
      case notes of all females presenting with nasal fractures over a five-year period
      (2004-2009) were retrospectively reviewed and the cited cause of the fracture was
      noted. RESULTS: From 2002 to 2009, there was an 825 per cent increase in nasal
      fractures in women aged 13-20 years. Almost one-quarter of all nasal fractures in
      one centre was attributed to non-domestic violence. The highest incidence of
      nasal fractures (67 per cent) was amongst white British females. CONCLUSION:
      There is an increasing trend in the number of women sustaining nasal fractures in
      the UK. The cause may be multi-factorial, but could be partially attributed to a
      rise in ladette culture. Further research on the role of alcohol consumption in
      this phenomenon is needed.

PMID- 24131899
TI  - The satisfaction with the quality of dementia care and the health, burnout and
      work ability of nurses: a longitudinal analysis of 50 German nursing homes.
AB  - BACKGROUND: The increasing prevalence of residents with dementia in Nursing Homes
      (NH) leads to a demanding work with high physical and psychological workloads.
      This study focuses on NH nurses and their satisfaction with quality of care for
      residents with dementia (SQCD) and its impact on nurses' general health, burnout
      and work ability. METHOD: Two-wave (2007/2009) self-report questionnaire data of
      305 nurses (RNs and nurses' aides) from 50 German NHs. RESULTS: 58.6% (2007) and
      64.9% (2009) of the respondents reported satisfaction with the quality of care of
      the dementia residents. However, when dissatisfied, this was perceived as
      substantial work stressor and was adversely associated with nurses' individual
      resource outcomes. Those nurses who between 2007 and 2009 had become dissatisfied
      or were dissatisfied at both measurements showed the most adverse scorings for
      burnout, general health and work ability. DISCUSSION: The findings imply that in
      NHs, SQCD may be a relevant work factor with substantial impact on nurses' core
      resources.

PMID- 24131901
TI  - Zero-temperature phase diagram of D2 physisorbed on graphane.
AB  - We determined the zero-temperature phase diagram of D2 physisorbed on graphane
      using the diffusion Monte Carlo method. The substrate used was C-graphane, an
      allotropic form of the compound that has been experimentally obtained through
      hydrogenation of graphene. We found that the ground state is the delta phase, a
      commensurate structure observed experimentally when D2 is adsorbed on graphite,
      and not the registered ?3 x ?3 structure characteristic of H2 on the same
      substrate.

PMID- 24131902
TI  - When ethical reform became law: the constitutional  concerns raised by recent
      legislation in Taiwan.
AB  - In an effort at ethical reform, Taiwan recently revised the Hospice Palliative
      Care Law authorising family members or physicians to make surrogate decisions to
      discontinue life-sustaining treatment if an incompetent terminally ill patient
      did not express their wishes while still competent. In particular, Article 7 of
      the new law authorises the palliative care team, namely the physicians, to act as
      sole decision-makers on behalf of the incompetent terminally ill patient's best
      interests if no family member is available. However, the law fails to provide
      guidance as to what constitutes the patient's best interests or what specific
      procedures the treating physicians should follow, and so has raised
      constitutional concerns. It may be difficult to translate ethical reform into law
      but it is not impossible if essential requirements are carefully followed. First,
      there must be substantial nexus between the purpose of the statute and the
      measures provided under the statute. Second, advocates need to convince the
      public that futility or waste has amounted to a public health emergency so as to
      justify lower procedural requirements. Third, a remedy or compensation should be
      available if the surrogate decisions have not been appropriately made.
      Fourth,minimum procedural safeguards are necessary even though the statute is
      intended to reduce the procedural burdens of making surrogate decisions on behalf
      of incompetent patients who lack family members and did not express their wishes
      while still competent.

PMID- 24131900
TI  - Prostaglandin E2 is critical for the development of niacin-deficiency-induced
      photosensitivity via ROS production.
AB  - Pellagra is a photosensitivity syndrome characterized by three "D's": diarrhea,
      dermatitis, and dementia as a result of niacin deficiency. However, the molecular
      mechanisms of photosensitivity dermatitis, the hallmark abnormality of this
      syndrome, remain unclear. We prepared niacin deficient mice in order to develop a
      murine model of pellagra. Niacin deficiency induced photosensitivity and severe
      diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated
      expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently,
      photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or
      blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin
      deficiency was mediated via ROS production in keratinocytes. In line with the
      above murine findings, human skin lesions of pellagra patients confirmed the
      enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was
      mediated through EP4 signaling in response to increased PGE2 production via
      induction of ROS formation.

PMID- 24131903
TI  - The ethics of peer review in bioethics.
AB  - A good deal has been written on the ethics of peer review, especially in the
      scientific and medical literatures. In contrast, we are unaware of any articles
      on the ethics of peer review in bioethics. Recognising this gap, we evaluate the
      extant proposals regarding ethical standards for peer review in general and
      consider how they apply to bioethics. We argue that scholars have an obligation
      to perform peer review based on the extent to which they personally benefit from
      the peer review process. We also argue, contrary to existing proposals and
      guidelines, that it can be appropriate for peer reviewers to benefit in their own
      scholarship from the manuscripts they review. With respect to bioethics in
      particular, we endorse double-blind review and suggest several ways in which the
      peer review process might be improved. 

PMID- 24131905
TI  - Effects of atomic scale roughness at metal/insulator interfaces on metal work
      function.
AB  - We evaluate the performance of different van der Waals (vdW) corrected density
      functional theory (DFT) methods in predicting the structure of perfect interfaces
      between the LiF(001), MgO(001), NiO(001) films on the Ag(001) surface and the
      resulting work function shift of Ag(001). The results demonstrate that including
      the van der Waals interaction is important for obtaining accurate interface
      structures and the metal work function shift. The work function shift results
      from a subtle interplay of several effects strongly affected by even small
      changes in the interface geometry. This makes the accuracy of theoretical methods
      insufficient for predicting the shift values better than within 0.2 eV. Most of
      the existing van der Waals corrected functionals are not particularly suited for
      studying metal/insulator interfaces. The lack of accurate experimental data on
      the interface geometries and surface rumpling of insulators hampers the
      calibration of existing and novel density functionals. 

PMID- 24131906
TI  - Systemic rheumatic diseases: beyond classification criteria.

PMID- 24131907
TI  - Cutaneous manifestations of antiphospholipid syndrome: a review of the clinical
      features, diagnosis and management.
AB  - Antiphospholipid syndrome is a relatively recent systemic autoimmune disorder
      defined by thrombotic events and/or obstetric complications in the presence of
      persistent elevated antiphospholipid antibodies. It?'s characterized by a wide
      spectrum of clinical presentations and virtually any organ system or tissue may
      be affected by the consequences of vascular occlusion. Diagnosis is sometimes
      difficult and although classification criteria have been published and revised
      there remain ongoing issues regarding nomenclature, expanding clinical features,
      laboratory tests and management and much still has to be done. Cutaneous
      manifestations are common and frequently the first sign of the disease. Although
      extremely diverse it?'s important to know which dermatological findings should
      prompt consideration of antiphospholipid syndrome and the appropriate management
      for those patients. Much has been debated about when to consider antiphospholipid
      syndrome and consensus still does not exist, however in spite of being a
      diagnostic challenge clinicians should know when to look for antiphospholipid
      antibodies since an early diagnosis is important to prevent further and serious
      complications. In this article we focus on the cutaneous features that should
      raise suspicion on the presence of antiphospholipid syndrome and on the complex
      management of such patients. Many other dermatological signs related to this
      syndrome have been described in the literature but only occasionally and without
      consistency or statistic impact and therefore will not be considered here.

PMID- 24131908
TI  - A glimpse from the past: osteoporosis and osteoporotic fractures in a Portuguese
      identified skeletal sample.
AB  - The diachronic variation of etiological factors, like longevity or diet, affected
      the prevalence of osteoporosis and the so-called osteoporotic fractures in the
      past. As such, it is important to understand the epidemiology of this disease in
      historical populations; with behaviors and customs that were unalike the modern
      westernized lifestyle. OBJECTIVES: The main objective of this study is to
      characterize the epidemiological patterns of osteoporosis and related fractures
      in an identified Portuguese skeletal sample from the mid 19th - early 20th
      centuries. MATERIALS AND METHODS: The sample studied comprised 196 skeletal
      individuals with known sex and age-at-death, housed at the University of Coimbra.
      Bone mineral density (BMD) was evaluated in the proximal femur through dual X-ray
      absorptiometry and osteoporotic fractures were recorded according to clinical and
      paleopathological protocols. RESULTS: BMD decreased significantly with age-at
      death, both at the ROI "Total hip" and the ROI "Neck". At the "Total hip", peak
      bone mass (PBM) was achieved early (20-29 years age group) in both sexes. In the
      study-group as a whole, BMD was significantly higher in males when compared to
      females. As expected, the prevalence of osteoporosis in the proximal femur is
      higher in women and rises steeply with age. Comparisons with two modern
      Portuguese samples showed an equivalent pattern of BMD reduction. Nonetheless,
      BMD is usually lower in the skeletal sample. Women with osteoporosis had a much
      larger probability of showing a fragility fracture than women diagnosed with
      "normal" BMD or osteopenia. CONCLUSIONS: In spite of enormous lifestyle
      differences, the epidemiological pattern of bone mass decrease in a Portuguese
      skeletal sample is strikingly similar to the ones observed in modern populations.
      This study adds further data to the recent notion that osteoporosis is a disease
      with deep roots in the past.

PMID- 24131909
TI  - Neurological involvement in Primary Sjogren Syndrome.
AB  - OBJECTIVES: To perform an observational retrospective cross-sectional case
      control study to evaluate prevalence, clinical patterns and outcomes of
      neurological involvement in a cohort of Primary Sjogren Syndrome (pSS) patients
      followed up in a single center. MATERIAL AND METHODS: From a total of 93 pSS
      patients, diagnosed according to the 2002 criteria proposed by the American
      European Consensus Group, we reviewed the clinical data of those with
      neurological complaints that were referred to observation by Neuroimmunology
      doctors. Demographic, clinical, seroimmunological data were compared between
      patients with and without neurological involvement. RESULTS: Neurological
      involvement was detected in 26 (28%) of the 93 patients. Neurological symptoms
      preceded the diagnosis of pSS in 12 (46%) patients. They were all females. The
      mean age at disease onset and neurological onset were 41,2 and 47,9 years,
      respectively. Twelve patients (46%) had peripheral system involvement (PNS), 13
      (50%) patients had central nervous involvement (CNS) disorders and one (4%)
      patient had both PNS and CNS involvement. In patients with PNS, pure sensory
      neuropathy (small fiber neuropathy confirmed by quantitative sensory testing and
      sural neuropathy) occurred most frequently (n =5), followed by cranial nerve
      involvement affecting trigeminal, facial, or trochlear nerves (n = 4). Multiple
      mononeuropathy (n = 1), sensorimotor polyneuropathy (n=1), autonomic neuropathy
      (n=1) and myasthenia gravis (n = 1), were also observed. In patients with CNS
      disorders, headache (n=3) occurred most frequently, in two patients with MRI
      abnormalities compatible with inflammatory disease. Spinal cord involvement
      (n=2), seizures (n = 2), motor and sensory deficit (n=2), movement disorders
      (n=2), neuromyelitis optica (n=2), aseptic meningitis (n=1) were others
      manifestations observed. Cognitive dysfunction was observed in 3 of these
      patients. The frequency of constitutional symptoms (such as fever and fatigue)
      and lung involvement was significantly higher (p< 0,05) and the articular
      symptoms were significantly less frequent (p< 0,05) in pSS with neurological
      involvement. The neurologic outcome was good in 77% of the patients. CONCLUSION:
      The current study underlines the diversity of neurologic complications of pSS.
      The frequency of neurologic manifestations as first manifestation of pSS,
      especially in the event of CNS involvement, could explain why SS is frequently
      under diagnosed or late diagnosed. Screening for SS should be systematically
      performed in cases of acute or chronic myelopathy, axonal sensorimotor
      neuropathy, or cranial nerve involvement.

PMID- 24131910
TI  - A seroimmunological profile of erosive hand osteoarthritis.
AB  - OBJECTIVES: erosive hand osteoarthritis (EHOA) is an inflammatory disorder
      involving joints of the hands, which may be accompanied by acute phase reactants.
      The relationship between EHOA and classical osteoarthritis (OA) is still
      controversial, since some authors consider EHOA as a distinct disease, other as a
      subset of OA, and some as a border entity between OA and rheumatoid arthritis
      (RA). Scarce data are available about the seroimmunological profile of the
      disease, which could aid to identify a possible role of the immune system in EHOA
      pathogenesis, and could also allow to better differentiate EHOA both from OA and
      RA. MATERIAL AND METHODS: blood was drawn from the following patients: 37 with
      EHOA, 35 with OA and 45 with RA. All sera were tested for rheumatoid factor, anti
      cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA),
      anti-extractable nuclear antigens (anti-ENA) and anti-neutrophil cytoplasmic
      antibodies (ANCA). RESULTS: ANCA were never detected in OA, whereas they were
      found in 7 (19%) EHOA and 8 (18%) RA patients; the difference between EHOA and OA
      was statistically significant (p<0.01). Anti-CCP antibodies, which were
      consistently negative in OA, were positive in 2 EHOA (5%) at a low titre and in
      23 (51%) RA patients, usually at a very high titre. The difference between EHOA
      and OA was not statistically significant, while the number of RA positive
      patients was significantly higher (p<0.001). CONCLUSIONS: our findings suggest
      that the seroimmunological profile of EHOA is different from that of OA. In EHOA
      patients ANCA and anti-CCP antibodies might be either markers of inflammation
      involving neutrophils and/or markers of an underlying autoimmune process.

PMID- 24131912
TI  - Concomitant alopecia areata and hypertrichosis after infliximab therapy: rara
      avis.
AB  - We present a 37 year-old man with HLA-B27 positive ankylosing spondylitis for the
      last 3 years. Interestingly, he developed both alopecia areata and hypertrichosis
      simultaneously following infliximab treatment. Reporting this interesting patient
      of ours -to our best notice for the first time in the literature- we call
      attention of clinicians to the contradistinctive effects of anti-TNF-alpha agents
      on hair growth cycle.

PMID- 24131911
TI  - Therapy of calcinosis universalis complicating adult dermatomyositis.
AB  - Although frequent in juvenile dermatomyositis, calcinosis is a rare finding in
      adult dermatomyositis. It has been associated with disease activity and delayed
      treatment. It is more common in later phases of the disease, in sites under
      chronic stress and trauma. Calcinosis has been associated with inflammation but
      information about its pathogeny continues to evolve as we learn more about the
      underlying processes. Being uncommon, there is no standard therapy and management
      is guided by case studies and series. Different treatments have been used in an
      attempt to clear calcinosis lesions and prevent its recurrence but none has been
      clearly effective. The authors present the case of a 25 year-old female diagnosed
      with dermatomyositis who developed calcinosis universalis after stopping therapy.
      Immunossupressive therapy was reinitiated and therapy aiming at reduction of
      calcinosis was sequentially tried using: colchicine, hydroxide magnesium,
      diltiazem, alendronate, probenecid and pamidronate. After receiving intravenous
      pamidronate, calcinosis lesions decreased and the patient regained full range of
      movement and quality of life. No recurrence has occurred after eight years of
      follow-up.

PMID- 24131913
TI  - Goldbloom's syndrome - a case report.
AB  - The Goldbloom's syndrome (GS) is a rare clinical condition of unknown aetiology,
      occurring exclusively in the pediatric population. It consists in an idiopathic
      periosteal hyperostosis with dysproteinemia, whose symptoms can mimic a
      neoplastic disease. We present a case report illustrating the diagnostic
      challenge of this condition. The exclusion of the common causes of bone pain,
      associated with generalized periostitis and increased gammaglobulins suggested
      the diagnosis of GS. The self-limited symptoms, the resolution of radiological
      findings in four months and the normalization of laboratory abnormalities within
      ten months, allowed to establish definitely the diagnosis of GS. GS must be
      considered when diffuse bone pain, prolonged fever and weight loss are present
      after exclusion of malignant disease with bone involvement.

PMID- 24131914
TI  - Sudden onset of cyanosis due to systemic onset juvenil idiopathic arthritis.

PMID- 24131915
TI  - Endothelin receptor antagonists and scleroderma related digital ulcers.

PMID- 24131917
TI  - Tuning CO2 electroreduction efficiency at Pd shells on Au nanocores.
AB  - The faradaic efficiency of CO2 electroreduction is significantly affected by the
      thickness of Pd nanoshells on Au cores. The ratio of hydrogen evolution to CO2
      reduction was determined by differential electrochemical mass spectrometry.
      Decreasing the Pd shell thickness from 10 to 1 nm leads to a twofold increase in
      faradaic efficiency. 

PMID- 24131916
TI  - In vitro anti-Herpes simplex virus activity of crude extract of the roots of
      Nauclea latifolia Smith (Rubiaceae).
AB  - BACKGROUND: Nauclea latifolia Smith, a shrub belonging to the family Rubiaceae is
      a very popular medicinal plant in Cameroon and neighboring countries where it is
      used to treat jaundice, yellow fever, rheumatism, abdominal pains, hepatitis,
      diarrhea, dysentery, hypertension, as well as diabetes. The ethno-medicinal use
      against yellow fever, jaundice and diarrhea prompted us to investigate on the
      antiviral activity of the root bark of N. latifolia. In this study, HSV-2 was
      chosen as a viral model because of its strong impact on HIV transmission and
      acquisition. METHODS: The crude extract under study was prepared by maceration of
      air-dried and powdered roots barks of N. latifolia in CH2Cl2/MeOH (50:50) mixture
      for 48 hours, then it was subjected to filtration and evaporation under vacuum. A
      phytochemical analysis of the crude extract was performed by High Performance
      Liquid Chromatography coupled with a photodiode array and mass spectrometry (HPLC
      PDA-ESI-qMS). The anti-HSV-2 activity was assayed in vitro by plaque reduction
      and virus yield assays and the major mechanism of action was investigated by
      virucidal and time of addition assays. Data values were compared using the Extra
      sum of squares F test of program GraphPad PRISM 4. RESULTS: The main components
      detected in the extract belong to the class of indole alkaloids characteristic of
      Nauclea genus. Strictosamide, vincosamide and pumiloside were tentatively
      identified together with quinovic acid glycoside. N. latifolia crude extract
      inhibited both acyclovir sensitive and acyclovir resistant HSV-2 strains, with
      IC50 values of 5.38 MUg/ml for the former and 7.17 MUg/ml for the latter. The
      extract was found to be most active when added post-infection, with IC50 of 3.63
      MUg/ml. CONCLUSION: The results of this work partly justify the empirical use of
      N. latifolia in traditional medicine for the treatment of viral diseases. This
      extract could be a promising rough material for the development of a new and more
      effective modern anti-HSV-2 medication also active against acyclovir-resistant
      HSV-2 strains.

PMID- 24131918
TI  - Bioactive bredigite coating with improved bonding strength, rapid apatite
      mineralization and excellent cytocompatibility.
AB  - Previous studies have shown that bredigite (Ca7MgSi4O16) bioceramics possessed
      excellent biocompatibility, apatite-mineralization ability and mechanical
      properties. In this paper, the bredigite coating on Ti-6Al-4 V substrate was
      prepared by plasma spraying technique. The main compositions of the coating were
      bredigite crystal phase with small parts of amorphous phases. The bonding
      strength of the coating to Ti-6Al-4 V substrate reached 49.8 MPa, which was
      significantly higher than that of hydroxyapatite coating and other silicate-based
      bioceramic coatings prepared by same method. After immersed in simulated body
      fluid for 2 days, a distinct apatite layer was deposited on the surface of
      bredigite coating, indicating that the prepared bredigite coating has excellent
      apatite-mineralization ability. The prepared bredigite coating supported the
      attachment and proliferation of rabbit bone marrow stem cells. The proliferation
      level of bone marrow stem cells was significantly higher than that on the
      hydroxyapatite coating. Our further study showed that the released SiO4 (4-) and
      Mg(2+) ions from bredigite coating as well as the formed nano-apatite layer on
      the coating surface might mainly contribute to the improvement of cell
      proliferation. The results indicated that the bredigite coating may be applied on
      orthopedic implants due to its excellent bonding strength, apatite mineralization
      and cytocompatibility.

PMID- 24131919
TI  - Pom1 is not the size ruler.

PMID- 24131920
TI  - Tumor suppression: putting p53 in context.

PMID- 24131921
TI  - Gfi1: a unique controller of T(reg) cells.

PMID- 24131922
TI  - mTOR/PRAS40 interaction: hypertrophy or proliferation.

PMID- 24131923
TI  - Neuronal migration re-purposes mechanisms of cytokinesis.

PMID- 24131924
TI  - PTEN sumo-wrestles human RAD52 to mystery land.

PMID- 24131925
TI  - The gene dosage of class Ia PI3K dictates the development of PTEN hamartoma tumor
      syndrome.
AB  - The PTEN hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline
      inactivating mutations of the tumor suppressor gene PTEN. Loss of PTEN function
      leads to unimpeded phosphatidylinositol-3'-kinase (PI3K) activity and PI3K-driven
      cell division. Individuals with PHTS develop benign hamartomas in various tissues
      and have an increased risk of developing malignant diseases. Notably, no
      effective therapy currently exists for this disorder. Using both genetic mouse
      models and pharmacological approaches, we recently demonstrated that PI3K
      p110alpha and p110beta isoforms play spatially distinct but concerted roles in
      the skin that are required for the development and maintenance of PHTS. We also
      show that treatment with a pan-PI3K inhibitor prevents the development of skin
      PHTS and reverses advanced-stage skin hamartomas in vivo. Here, we report that
      genetic ablation of only 3 out of 4 p110 alleles is sufficient to block the
      development of skin hamartomas resulting from the complete loss of Pten in mice.
      Similar to our findings in skin, we now also show that mammary gland neoplastic
      lesions can be prevented or reversed upon PI3K inhibition in our PHTS mouse
      model. Our data suggest a possible route to chemoprevention using reduced doses
      of PI3K inhibitors for PTEN-deficient carrier patients. 

PMID- 24131928
TI  - Nanoporous metal formates for krypton/xenon separation.
AB  - Metal(II) formates (Co and Ni) show a significantly larger heat of adsorption for
      xenon than krypton across all loadings due to size selectivity in the primary
      adsorption site.

PMID- 24131926
TI  - Coordinated regulation of p31(Comet) and Mad2 expression is required for cellular
      proliferation.
AB  - p31(Comet) is a well-known interacting partner of the spindle assembly checkpoint
      (SAC) effector molecule Mad2. At the molecular level it is well established that
      p31(Comet) promotes efficient mitotic exit, specifically the metaphase-anaphase
      transition, by antagonizing Mad2 function. However, there is little knowledge of
      how p31(Comet) is regulated or the physiological importance of controlling
      p31(Comet). Here, we show that the Rb-E2F pathway regulates p31(Comet)
      expression. In multiple tumor types (including breast and lung) p31(Comet)
      expression is increased along with Mad2. Expression of this antagonist-target
      pair is coordinated in cells and correlated in cancer. Moreover, a narrow range
      of p31(Comet):Mad2 ratios is compatible with cellular viability. Our data suggest
      that coordinate regulation is important for the outgrowth of oncogenic cell
      populations. Our findings suggest that altered p31(Comet):Mad2 expression ratios
      may provide new insight into altered SAC function and the generation of
      chromosomal instability in tumors. 

PMID- 24131927
TI  - High expression of leptin receptor leads to temozolomide resistance with
      exhibiting stem/progenitor cell features in gliobalastoma.
AB  - Glioblastoma is a highly aggressive malignant disease with notable resistance to
      chemotherapy. In this study, we found that leptin receptor (ObR)-positive
      glioblastoma cells were resistant to temozolomide (TMZ), and TMZ-resistant cells
      exhibited high expression of ObR. ObR can serve as a marker to enrich
      glioblastoma cells with some stem/progenitor cell traits, which explained the
      reason for TMZ resistance of ObR+ cells. STAT3-mediated SOX2/OCT4 signaling axis
      maintained the stem/progenitor cell properties of ObR+ cells, which indirectly
      regulated glioblastoma TMZ resistance. These findings gain insight into the
      molecular link between obesity and glioblastoma, and better understanding of this
      drug-resistant population may lead to the development of more effective
      therapeutic interventions for glioblastoma. 

PMID- 24131930
TI  - Sign-inverted response of aluminum work function to tangential strain.
AB  - We have investigated the response of the work function, W, of low-index aluminum
      surfaces to tangential strain by using first-principles calculations based on
      density functional theory. This response parameter is a central quantity in
      electrocapillary coupling of metal electrodes relating to the performance of
      porous metal actuators and surface stress based sensing devices. We find that Al
      surfaces exhibit a positive response for all orientations considered. By
      contrast, previous studies reported negative-valued response parameters for clean
      surfaces of several transition metals. We discuss separately the response of W to
      different types of strain and the impact of the strain on the Fermi energy and
      the surface dipole. We argue that the reason for the abnormal positive sign of
      the Al response parameter lies in its high valence electron density.

PMID- 24131929
TI  - Deriving at candidate genes of metabolic stress from pancreas of WNIN/GR-Ob
      mutant rats.
AB  - Development of appropriate animal model systems have greatly helped our
      understanding of the basic mechanism(s) of several degenerative diseases. WNIN/GR
      Ob?a mutant rat strain developed at the National Center for Laboratory Animal
      Sciences facility of National Institute of Nutrition, is a new animal model ideal
      to study the metabolic syndrome since it is obese with impaired glucose tolerance
      and also exhibits several secondary complications. The present study was
      performed in the pancreas of this mutant model to assess the global gene
      expression (microarray) to assess the transcriptome level changes in situ
      depicting inflammation, obesity, insulin resistance, and diabetes in these
      animals. Our findings suggest an interplay of several confounding factors in
      pancreas which include inflammation /macrophage infiltration/apoptosis/oxidative
      and endoplasmic reticulum stress, all contributing for the shift toward pro
      inflammation. We were able to phenotypically correlate the metabolic alterations
      vis-a-vis candidate genes (array analyses) compared between mutants and its age
      matched, parental controls. We advocate that the data reported here would provide
      a suitable insight in to the pathophysiology of metabolic syndrome . 

PMID- 24131931
TI  - Versatile supramolecular pH-tolerant hydrogels which demonstrate pH-dependent
      selective adsorption of dyes from aqueous solution.
AB  - We report a novel gelator functionalised with hydrazides (as replacements for
      carboxylic acids) which, as a result, is able to assemble into hydrogels across a
      wide pH range - this gelator exhibits pH-switchable dye adsorption-desorption
      dependent on protonation of the target dyes and their resulting interactions with
      the self-assembled gel nanofibres. 

PMID- 24131932
TI  - Surgery for acquired cardiovascular disease: antiseptic treatment of contaminated
      vein grafts.
AB  - AIM: Saphenous vein grafts harvested for use as bypass conduits can be
      contaminated intraoperatively, e.g. by being inadvertently dropped to the floor
      of the operating room (OR). This study was performed to investigate
      microorganisms most likely contaminating vein grafts and to assess the possible
      efficacy of measures to treat potentially contaminated vein grafts antiseptically
      for further use. METHODS: In a first step we determined the microbiological flora
      of the OR using surface cultures and cultures from intentionally dropped vein
      grafts. Several antiseptic agents (PVP-iodine 10%, octenidinhydrochloride 0.1%,
      polyhexanide 1%) were evaluated for their in vitro efficacy to disinfect
      artificially contaminated vein segments. The most promising antiseptic regimen
      was tested on veins contaminated in a real OR setting. Finally, we tested for
      possible alterations in mechanical properties of the veins caused by antiseptic
      treatment. RESULTS: Coagulase-negative staphylococci where the predominant
      bacteria recovered from the OR with 59.9%. Antiseptic treatment with a
      combination of octenidine and PVP-iodine resulted in a higher rate of negative
      cultures than any single agent. Treatment of 50 saphenous vein grafts
      contaminated in the OR with the combination regimen resulted in only 3 positive
      cultural results within 7 days. Mechanical tear-stress testing comparing
      antiseptically treated vein grafts with controls showed no difference in their
      resistance to tear stress. CONCLUSION: Antiseptic treatment of contaminated vein
      grafts was shown to be effective in a high percentage of cases without altering
      mechanical properties of grafts and may be an option for the surgeon in case of a
      contamination.

PMID- 24131933
TI  - Huge postmyocardial infarction left ventricular pseudoaneurysm in a patient with
      previous self-inflicted thoracic stab wounds.

PMID- 24131934
TI  - Clinical course after surgical treatment of active isolated native mitral valve
      endocarditis.
AB  - AIM: Isolated mitral valve endocarditis (MVE) forms a particular subgroup within
      native infective valve endocarditis (NVE). We characterized this particular
      subgroup and analyzed the course of patients undergoing cardiac surgery. METHODS:
      Between 1997 and 2011, 474 patients underwent cardiac surgery at our institution
      for NVE treatment. Of these, 89 patients (18.8%) suffered from MVE. Valve
      replacement was undertaken in 84.2% and valve repair in 15.8%. Follow-up was
      completed with 267 patient years. RESULTS: A delay between the onset of first
      symptoms and surgery of 4.7+/-1.2 weeks was observed. Hence, most patients were
      in a critical preoperative state characterized by severe sepsis and destruction
      of the mitral valve. About 19.4% were emergency procedures. The MVE group
      presented with a higher prevalence of preoperative stroke, atrial fibrillation,
      coronary artery disease and chronic obstructive pulmonary disease in comparison
      with remaining NVE cases. MVE was more likely caused by Staphylococcus aureus;
      Staphylococcus epidermidis and Staphylococcus viridans were less frequent (P<0.01
      each). Early mortality (6.7%) was caused by persistent sepsis. ICU stay >7 days
      and time on artificial ventilation >40 h led to a higher risk of in-hospital
      death. Five-year survival was 59.6% and affected by extracardiac comorbidities.
      CONCLUSION: Isolated MVE was characterized by a long delay before surgery,
      differences in microbiological findings and a higher prevalence of preoperative
      strokes in comparison to NVE. Surgery for MVE can be conducted with good clinical
      results, but mid-term outcome is limited by extracardiac comorbidities.

PMID- 24131936
TI  - Stereospecific synthesis of resorcin[4]arenes and pyrogallol[4]arenes in dynamic
      thin films.
AB  - Acid catalysed condensation of resorcinol and pyrogallol with aromatic aldehydes
      using a microfluidic vortex fluidic device (VFD) under continuous flow conditions
      results in the selective formation of resorcin[4]arenes and pyrogallol[4]arenes
      as predominantly their C(4v) isomers. Notably C(2v) isomers and C(2h) isomers can
      be also prepared with the latter being converted to the C(4v) isomer when the VFD
      operates in confined mode.

PMID- 24131937
TI  - Magnetocaloric effect of a series of remarkably isostructural intermetallic
      [Ni(II)3Ln(III)] cubane aggregates.
AB  - A new series of remarkably isostructural 3d-4f compounds,
      [Ni3Ln(hmp)4(OAc)5].H2O.CH2Cl2 (Ln = Gd (1), Tb (2), Dy (3), Ho (4), Y (5)) were
      synthesized based on a simple one-pot self-assembly method. Magnetic measurements
      demonstrated the ferromagnetic property of the [Ni3Ln] cores and the
      heterometallic influence on the magnetocaloric properties. This study suggested
      that robust and discrete intermetallic cubanes can be an alternative to other
      magnetically active materials such as high-nuclearity aggregates or clusters
      whose structures are not generally controlled by common synthetic methodological
      designs.

PMID- 24131935
TI  - How does cancer cell metabolism affect tumor migration and invasion?
AB  - Cancer metastasis is the major cause of cancer-associated death. Accordingly,
      identification of the regulatory mechanisms that control whether or not tumor
      cells become "directed walkers" is a crucial issue of cancer research. The
      deregulation of cell migration during cancer progression determines the capacity
      of tumor cells to escape from the primary tumors and invade adjacent tissues to
      finally form metastases. The ability to switch from a predominantly oxidative
      metabolism to glycolysis and the production of lactate even when oxygen is
      plentiful is a key characteristic of cancer cells. This metabolic switch, known
      as the Warburg effect, was first described in 1920s, and affected not only tumor
      cell growth but also tumor cell migration. In this review, we will focus on the
      recent studies on how cancer cell metabolism affects tumor cell migration and
      invasion. Understanding the new aspects on molecular mechanisms and signaling
      pathways controlling tumor cell migration is critical for development of
      therapeutic strategies for cancer patients. 

PMID- 24131938
TI  - Ultrafast modulation of polarization amplitude by terahertz fields in electronic
      type organic ferroelectrics.
AB  - Ferroelectrics sometimes show large electro-optical and non-linear optical
      effects, available for polarization rotation and frequency conversion of light,
      respectively. If the amplitude of ferroelectric polarization is modulated in the
      picosecond time domain, terahertz repetition of optical switching via electro
      optical and non-linear optical effects would be achieved. Here we show that
      polarization amplitude can be rapidly modulated by a terahertz electric field in
      an organic ferroelectric, tetrathiafulvalene-p-chloranil (TTF-CA). In this
      compound, alternately stacked donor (TTF) and acceptor (CA) molecules are
      dimerized via the spin-Peierls mechanism, and charge transfer within each dimer
      results in a new type of ferroelectricity called electronic-type
      ferroelectricity. Using a terahertz field, the intradimer charge transfer is
      strongly modulated, producing a subpicosecond change in the macroscopic
      polarization, which is demonstrated by transient reflectivity and second-harmonic
      generation measurements. Subsequently, coherent oscillation of the dimeric
      molecular displacements occur, which is explained by the modulation of the spin
      moment of each molecule. 

PMID- 24131939
TI  - Back-scatter based whispering gallery mode sensing.
AB  - Whispering gallery mode biosensors allow selective unlabelled detection of single
      proteins and, combined with quantum limited sensitivity, the possibility for
      noninvasive real-time observation of motor molecule motion. However, to date
      technical noise sources, most particularly low frequency laser noise, have
      constrained such applications. Here we introduce a new technique for whispering
      gallery mode sensing based on direct detection of back-scattered light. This
      experimentally straightforward technique is immune to frequency noise in
      principle, and further, acts to suppress thermorefractive noise. We demonstrate
      27 dB of frequency noise suppression, eliminating frequency noise as a source of
      sensitivity degradation and allowing an absolute frequency shift sensitivity of
      76 kHz. Our results open a new pathway towards single molecule biophysics
      experiments and ultrasensitive biosensors.

PMID- 24131940
TI  - Elucidating the mechanism behind the stabilization of multi-charged metal cations
      in water: a case study of the electronic states of microhydrated Mg2+, Ca2+ and
      Al3+.
AB  - Metal atoms typically have second and higher ionization potentials (IPs) that are
      larger than the IP of water, resulting in the Coulombic explosion of the first
      few [M(H2O)n](+q) (q>= 2) gas phase clusters as the M(+(q-1)) + (H2O)n(+) or
      MOH(+(q-1)) + H3O(+)(H2O)n-2 energy levels are energetically more stable than the
      M(q+) + (H2O)n ones for small n. We present a theoretical analysis of the various
      electronic states arising from the sequential hydration of the Ca(2+), Mg(2+) and
      Al(3+) cations with up to six water molecules. Our results quantify the relative
      shift of those electronic states with the degree of solvation, identify their
      complex interaction with other states arising from different dissociation
      channels and shed light on the mechanism behind the energetic stabilization of
      the multi-charged hydrated M(+q)(H2O)n complexes observed in aqueous solution
      with respect to the water ionization products. 

PMID- 24131941
TI  - Evaluation of dead-time corrections for post-radionuclide-therapy (177)Lu
      quantitative imaging with low-energy high-resolution collimators.
AB  - OBJECTIVES: Dead-time (DT) effects rarely cause problems in diagnostic single
      photon emission computed tomography (SPECT) studies; however, in post
      radionuclide-therapy imaging, DT can be substantial. Therefore, corrections may
      be necessary if quantitative images are used in image-based dosimetry or for
      evaluation of therapy outcomes. This task is particularly challenging if low
      energy collimators are used. Our goal was to design a simple method to determine
      the dead-time correction factor (DTCF) without the need for phantom experiments
      and complex calculations. METHODS: Planar and SPECT/CT scans of a water phantom
      containing a 70 ml bottle filled with lutetium-177 (Lu) were acquired over 60
      days. Two small Lu markers were used in all scans. The DTCF based on the ratio of
      observed to true count rates measured over the entire spectrum and using
      photopeak primary photons only was estimated for phantom (DT present) and marker
      (no DT) scans. In addition, variations in counts in SPECT projections
      (potentially caused by varying bremsstrahlung and scatter) were investigated.
      RESULTS: For count rates that were about two-fold higher than typically seen in
      post-therapy Lu scans, the maximum DTCF reached a level of about 17%. The DTCF
      values determined directly from the phantom experiments using the total energy
      spectrum and photopeak counts only were equal to 13 and 16%, respectively. They
      were closely matched by those from the proposed marker-based method, which uses
      only two energy windows and measures photopeak primary photons (15-17%).
      CONCLUSION: A simple, marker-based method allowing for determination of the DTCF
      in high-activity Lu imaging studies has been proposed and validated using phantom
      experiments.

PMID- 24131943
TI  - DNA vaccines onward and upward! 20 years and counting! Highlights of the DNA
      vaccines 2012 meeting.

PMID- 24131942
TI  - Comparing approaches to correct for respiratory motion in NH3 PET-CT cardiac
      perfusion imaging.
AB  - AIM: Respiratory motion affects cardiac PET-computed tomography (CT) imaging by
      reducing attenuation correction (AC) accuracy and by introducing blur. The aim of
      this study was to compare three approaches for reducing motion-induced AC errors
      and evaluate the inclusion of respiratory motion correction. MATERIALS AND
      METHODS: AC with a helical CT was compared with averaged cine and gated cine CT,
      as well as with a pseudo-gated CT, which was produced by applying PET-derived
      motion fields to the helical CT. Data-driven gating was used to produce
      respiratory-gated PET and CT images, and 60 NH3 PET scans were attenuation
      corrected with each of the CTs. Respiratory motion correction was applied to the
      gated and pseudo-gated attenuation-corrected PET images. RESULTS: Anterior and
      lateral wall intensity measured in attenuation-corrected PET images generally
      increased when PET-CT alignment improved and decreased when alignment degraded.
      On average, all methods improved PET-CT liver and cardiac alignment, and
      increased anterior wall intensity by more than 10% in 36, 33 and 25 cases for the
      averaged, gated and pseudo-gated CTAC PET images, respectively. However, cases
      were found where alignment worsened and severe artefacts resulted. This occurred
      in more cases and to a greater extent for the averaged and gated CT, where the
      anterior wall intensity reduced by more than 10% in 21 and 24 cases,
      respectively, compared with six cases for the pseudo-gated CT. Application of
      respiratory motion correction increased the average anterior and inferior wall
      intensity, but only 13% of cases increased by more than 10%. CONCLUSION: All
      methods improved average respiratory-induced AC errors; however, some severe
      artefacts were produced. The pseudo-gated CT was found to be the most robust
      method.

PMID- 24131944
TI  - Neck lump clinics: is on-site assessment of fine needle aspirate diagnostic
      adequacy cost-effective?
AB  - OBJECTIVES: To establish the diagnostic adequacy of ultrasound-guided fine needle
      aspiration cytology samples at the East Berkshire neck lump clinic, and to
      perform a cost-benefit analysis related to the hypothetical addition of an on
      site cytology technician (required to review fine needle aspiration specimen
      adequacy). METHOD: The adequacy of all ultrasound-guided fine needle aspiration
      procedures was reviewed from 1 January to 30 June 2011. These results were used
      in the cost-benefit analysis related to on-site cytology assessment. RESULTS: Of
      the 307 ultrasound-guided fine needle aspiration cytology procedures performed
      over 6 months, 67 (22 per cent) were reported to be non-diagnostic. Operator
      experience was found to correlate significantly with diagnostic adequacy (p <
      0.001). Only 5 per cent of all fine needle aspirations were initially non
      diagnostic but diagnostic on repeat sampling. This suggests that the financial
      and time costs of on-site fine needle aspirate adequacy assessment would outweigh
      any benefit. CONCLUSION: In this series, the experience of individuals performing
      fine needle aspirations was the most important factor related to adequacy.

PMID- 24131946
TI  - Development of a multilocus sequence typing scheme for Streptococcus
      gallolyticus.
AB  - Streptococcus gallolyticus is often found as a member of the normal gut
      microflora in various animals. However, it has been reported to cause mastitis in
      cattle, septicaemia in pigeons, and meningitis, septicaemia and endocarditis in
      humans. However, little is known about the epidemiology and crucial virulence
      factors of S. gallolyticus. To help address these issues, we developed a
      multilocus sequence typing (MLST) scheme for S. gallolyticus. Seven housekeeping
      gene fragments were sequenced from each of 58 S. gallolyticus isolates collected
      from diverse origins and sources. The MLST scheme had good discriminatory
      ability. The 63 strains, including the 5 whole genome sequenced strains examined,
      resolved into 57 sequence types (STs), with 52 STs represented by only a single
      strain. With respect to the identification of S. gallolyticus subspecies (i.e. S.
      gallolyticus subsp. gallolyticus, S. gallolyticus subsp. pasteurianus and S.
      gallolyticus subsp. macedonicus), the results of biochemical tests and DNA-DNA
      hybridization were in high concordance with those of the MLST scheme. The MLST
      scheme developed in this study may be a useful tool capable of replacing the
      conventional methods used for S. gallolyticus subspecies identification. The
      results of this study suggest that the biology and virulence of two pathogenic S.
      gallolyticus subspecies (i.e. S. gallolyticus subsp. gallolyticus and S.
      gallolyticus subsp. pasteurianus) are very different. The MLST scheme offers
      researchers a valuable typing tool that will promote further investigation of the
      epidemiology of S. gallolyticus. 

PMID- 24131947
TI  - Static or breakloose friction for lubricated contacts: the role of surface
      roughness and dewetting.
AB  - We present experimental data for the static or breakloose friction for lubricated
      elastomer contacts, as a function of the time of stationary contact. Due to fluid
      squeeze-out from the asperity contact regions, the breakloose friction force
      increases continuously with the time of stationary contact. We consider three
      different cases: (a) PDMS rubber balls against flat smooth glass surfaces, (b)
      PDMS cylinder ribs against different substrates (glass, smooth and rough PMMA and
      an inert polymer) and (c) application to syringes. Due to differences in the
      surface roughness and contact pressures the three systems exhibit very different
      time dependences of the breakloose friction. In case (a) for rough surfaces the
      dry contact area A is a small fraction of the nominal contact area A0, and the
      fluid squeeze-out is fast. In case (b) the dry contact area is close to the
      nominal contact area, A/A0 ~ 1, and fluid squeeze-out is very slow due to
      percolation of the contact area. In this case, remarkably, different fluids with
      very different viscosities, ranging from 0.005 Pa s (water-glycerol mixture) to
      1.48 Pa s (glycerol), give very similar breakloose friction forces as a function
      of the time of stationary contact. In case (c) the contact pressure and the
      surface roughness are larger than in case (b), and the squeeze-out is very slow
      so that even after a very long time the area of real contact is below the
      percolation threshold. For all cases (a)-(c), the increase in the breakloose
      friction is mainly due to the increase in the area of real contact with
      increasing time, because of the fluid squeeze-out and dewetting.

PMID- 24131948
TI  - Primary basal cell carcinoma of the caruncle: case report and review of the
      literature.
AB  - A case of primary basal cell carcinoma of the caruncle is presented and patients
      presented in the literature reviewed. Clinical features and outcome of a patient
      with primary basal cell carcinoma of the caruncle is described. Review of 8 other
      cases identified through literature search with the keywords of "basal cell
      carcinoma" and "caruncle" is presented.A 67-year-old male patient presented with
      a 12 months' history of a lesion over the caruncular region. Incisional biopsy of
      the lesion revealed primary basal cell carcinoma of nodular type. MRI of the
      orbit identified extension of the lesion into the medial orbit. The tumor was
      excised, and reconstructive surgery was performed. The patient declined
      subsequent radiotherapy. No recurrence was detected during the follow up of 33
      months. The current patient and 8 other patients with primary basal cell
      carcinoma of the caruncle were reviewed.The main therapeutic approach for primary
      basal cell carcinoma of the caruncle is complete excision with tumor-free
      surgical margins. Adjuvant radiotherapy or chemotherapy may be administered when
      deemed necessary. 

PMID- 24131949
TI  - Crystal-storing histiocytosis masquerading ocular adnexal lymphoma: a case report
      and review of literature.
AB  - A case of crystal-storing histiocytosis (CSH) associated with mucosa-associated
      lymphoid tissue (MALT) lymphoma of orbit is reported. The patient was a 53-year
      old man who presented with an 8-year history of a slowly enlarging tumor in his
      right orbit. Histopathologic examination revealed that the tumor was composed
      predominantly of sheets of spindle-shaped cells resembling striated muscle cells
      and scattered aggregates of atypical lymphoid cells, showing prominent
      plasmacytoid differentiation. Immunohistochemical analysis demonstrated that the
      spindle-shaped cells were CD68-positive histiocytes containing abundant crystals
      in their cytoplasm, consistent with the diagnosis of CSH. The aggregates of
      atypical lymphoid cells were diagnosed as MALT lymphoma based on their
      immunophenotype. Although CSH is a well-recognized manifestation in
      lymphoproliferative disorders, CSH complicated by MALT type of ocular adnexal
      lymphoma has rarely been reported. Given the rarity of this, every case
      presenting with such crystal-storing histiocytes warrants a thorough search for a
      hidden lymphoid dyscrasia. 

PMID- 24131950
TI  - Lenz micropthalmia syndrome with associated orbital cysts.
AB  - An 8-year-old boy presented for oculoplastic evaluation of bilateral
      microphthalmia. He had multiple other congenital anomalies, including
      microcephaly, wide-spaced teeth, sloping shoulders, protruding ears, syndactyly,
      a posterior urethral valve, cystic dysplasia of the kidneys, and a bicuspid
      aortic valve. Taken together, these findings supported the diagnosis of Lenz
      microphthalmia syndrome. CT of the orbits revealed bilateral microphthalmic
      globes with associated colobomatous cysts. To the authors' knowledge, this is the
      first reported case of Lenz microphthalmia syndrome with associated orbital
      cysts. 

PMID- 24131951
TI  - Programming adaptive control to evolve increased metabolite production.
AB  - The complexity inherent in biological systems challenges efforts to rationally
      engineer novel phenotypes, especially those not amenable to high-throughput
      screens and selections. In nature, increased mutation rates generate diversity in
      a population that can lead to the evolution of new phenotypes. Here we construct
      an adaptive control system that increases the mutation rate in order to generate
      diversity in the population, and decreases the mutation rate as the concentration
      of a target metabolite increases. This system is called feedback-regulated
      evolution of phenotype (FREP), and is implemented with a sensor to gauge the
      concentration of a metabolite and an actuator to alter the mutation rate. To
      evolve certain novel traits that have no known natural sensors, we develop a
      framework to assemble synthetic transcription factors using metabolic enzymes and
      construct four different sensors that recognize isopentenyl diphosphate in
      bacteria and yeast. We verify FREP by evolving increased tyrosine and isoprenoid
      production. 

PMID- 24131952
TI  - Fluorinated metal-organic frameworks of 1,4-bis(1,2,4-triazol-1-ylmethyl)-2,3,5,6
      tetrafluorobenzene: synergistic interactions of ligand isomerism and
      counteranions.
AB  - A fluorinated bis(triazole) ligand, 1,4-bis(1,2,4-triazol-1-ylmethyl)-2,3,5,6
      tetrafluorobenzene (Fbtz), was applied to coordinate with a series of Mn(II),
      Co(II), Fe(II), and Cu(II) ions, respectively. In comparison with its
      nonfluorinated analogue 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene (btx), Fbtz is
      able to build six novel metal-organic frameworks by acting as a versatile bridge
      combining with the terminal chlorides (1-5) or acetates (6) ligands. The solid
      state crystal structures of 1-6 are studied by single-crystal X-ray
      crystallography to form the following structures: 3D polymers [M(Fbtz)2Cl2]n (1:
      M = Mn, 2: M = Co), 1D double chain polymers {[M(Fbtz)2Cl2].CH2Cl2.xH2O}n (3: M =
      Co, x = 1; 4: M = Fe, x = 2), {[Cu(Fbtz)2Cl2].4H2O}n (5), and a 1D double
      stranded helical polymer {[Cu2(Fbtz)(OAc)2].2H2O}n (6). Conformations of Fbtz in
      1-6 can be tuned as a result of varying the anions or solvent system, which
      ultimately form a series of novel coordination frameworks with different
      supramolecular architectures. The antibacterial activities of all complexes are
      investigated. Complexes 4 and 5 show a wide range of bactericidal activities to
      Gram positive (B. subtilis and S. aureus) and negative (E. coli and P.
      fluorescence) bacterial strains. The synergistic interactions of ligand isomerism
      and counteranions have profound effects on the supramolecular networks and
      properties. 

PMID- 24131953
TI  - Study of underpotential deposited Cu layers on Pt(111) and their stability
      against CO and CO2 in perchloric acid.
AB  - The underpotential deposition (UPD) of copper on a Pt(111) electrode and the
      influence of gas coadsorbates, i.e. CO and CO2, on the thus deposited copper
      layer were studied in a 0.1 M HClO4 electrolyte by means of EC-STM. By UPD, an
      atomically flat Cu layer is formed, which exhibits a pseudomorphic (1 * 1)
      structure. However, it contains several point defects due to which its total
      coverage is less than a monolayer, in agreement with the measured charge density
      in the CV curves. Upon exposure to a CO-saturated solution the pseudomorphic
      structure collapses to a coalescent structure with many vacancy islands. This
      phase transition is induced by the preferential binding of CO to the Pt(111)
      surface. In contrast, CO2, which binds stronger to copper, does not affect the
      pseudomorphic structure of the Cu layer. 

PMID- 24131954
TI  - Towards ultrahigh volumetric capacitance: graphene derived highly dense but
      porous carbons for supercapacitors.
AB  - A small volumetric capacitance resulting from a low packing density is one of the
      major limitations for novel nanocarbons finding real applications in commercial
      electrochemical energy storage devices. Here we report a carbon with a density of
      1.58 g cm(-3), 70% of the density of graphite, constructed of compactly
      interlinked graphene nanosheets, which is produced by an evaporation-induced
      drying of a graphene hydrogel. Such a carbon balances two seemingly incompatible
      characteristics: a porous microstructure and a high density, and therefore has a
      volumetric capacitance for electrochemical capacitors (ECs) up to 376 F cm(-3),
      which is the highest value so far reported for carbon materials in an aqueous
      electrolyte. More promising, the carbon is conductive and moldable, and thus
      could be used directly as a well-shaped electrode sheet for the assembly of a
      supercapacitor device free of any additives, resulting in device-level high
      energy density ECs.

PMID- 24131955
TI  - Horizontal gene transfer converts non-toxigenic Clostridium difficile strains
      into toxin producers.
AB  - Clostridium difficile is a major nosocomial pathogen and the main causative agent
      of antibiotic-associated diarrhoea. The organism produces two potent toxins, A
      and B, which are its major virulence factors. These are chromosomally encoded on
      a region termed the pathogenicity locus (PaLoc), which also contains regulatory
      genes, and is absent in non-toxigenic strains. Here we show that the PaLoc can be
      transferred from the toxin-producing strain, 630Deltaerm, to three non-toxigenic
      strains of different ribotypes. One of the transconjugants is shown by
      cytotoxicity assay to produce toxin B at a similar level to the donor strain,
      demonstrating that a toxigenic C. difficile strain is capable of converting a non
      toxigenic strain to a toxin producer by horizontal gene transfer. This has
      implications for the treatment of C. difficile infections, as non-toxigenic
      strains are being tested as treatments in clinical trials. 

PMID- 24131957
TI  - Compositional effects on the hydrogen storage properties of Mg(NH2)2-2LiH-xKH and
      the activity of KH during dehydrogenation reactions.
AB  - Potassium hydride (KH) was directly added to a Mg(NH2)2-2LiH system to improve
      the hydrogen storage properties; the corresponding mechanisms were elucidated.
      The Mg(NH2)2-2LiH-0.08KH composite displays optimized hydrogen-storage
      properties, reversibly storing approximately 5.2 wt% hydrogen through a two-stage
      reaction and a dehydrogenation onset at 70  degrees C. The 0.08KH-added sample
      fully dehydrogenated at 130  degrees C begins to absorb hydrogen at 50  degrees
      C, and takes up approximately 5.1 wt% of hydrogen at 140  degrees C. Adding KH
      significantly enhances the de-/hydrogenation kinetic properties; however, an
      overly rapid hydrogenation rate enlarges the particle size and raises the
      dehydrogenation temperature. A cycling evaluation reveals that the KH-added
      Mg(NH2)2-2LiH system possesses good reversible hydrogen storage abilities,
      although the operational temperatures for de-/hydrogenation increase during
      cycling. Detailed mechanistic investigations indicate that adding KH
      catalytically decreases the activation energy of the first dehydrogenation step
      and reduces the enthalpy of desorption during the second dehydrogenation step as
      a reactant, significantly improving the hydrogen storage properties of Mg(NH2)2
      2LiH. 

PMID- 24131956
TI  - Intermediary quantitative traits--an alternative in the identification of disease
      genes in asthma?
AB  - Intermediary quantitative traits are a possible alternative for the
      identification of disease genes. This may be particularly relevant when
      diagnostic criteria are not very well defined as described for asthma. We
      analyzed serum samples from 944 individuals of 218 asthma families for 17
      cytokines (eotaxin, GM-CSF, IFNgamma, IL1B, IL1RA, IL-4, IL-5, IL-6, IL-8, IL-10,
      IL-12(p40), IL-13, IL-17, IL-23, IL-33, TSLP and TNF-alpha) and determined the
      heritability. Linked chromosomal regions were identified by a genome-wide
      analysis using 334 autosomal microsatellite marker and association tested by
      further 550 SNP marker at genes implicated earlier with immune response.
      Heritability varied with TNF-alpha and IL-8 levels having the highest and TSLP
      having the lowest heritability. Linkage was significantly increased only for IL
      12(p40) at D17S949. There were multiple significant single-nucleotide
      polymorphisms (SNP) associations (P<0.05) as found in the transmission
      disequilibrium test, whereas only a few replicated in parents or children only.
      These include SNPs in IL1RN that were associated with IL-33 and TSLP levels, and
      a SNP in NR3C2 that was associated with eotaxin, IL-13 and IFN-gamma levels.
      Circulating level of serum cytokines exhibits genetic associations with asthma
      traits that are otherwise not detected using clinical diagnosis or when the
      clinical details are ambiguous. 

PMID- 24131958
TI  - Detection of hepatitis B virus in the cerumen of patients with chronic hepatitis
      B infection.
AB  - OBJECTIVE: To investigate hepatitis B virus DNA in the cerumen of hepatitis B
      virus infected patients. METHODS: This study comprised 30 confirmed cases of
      chronic hepatitis B. Patients' serum samples were examined for hepatitis B
      surface antigen and antibodies using enzyme immunoassay systems. The presence of
      hepatitis B virus DNA in cerumen was investigated using a polymerase chain
      reaction test. RESULTS: All of the samples were positive for hepatitis B surface
      antigen and negative for hepatitis B surface antibodies. Hepatitis virus DNA was
      detected in two cerumen samples (6.6 per cent of patients). CONCLUSION: Cerumen
      can be a potential source of transmission of hepatitis B virus.

PMID- 24131959
TI  - Thermal transport across metal-insulator interface via electron-phonon
      interaction.
AB  - The thermal transport across a metal-insulator interface can be characterized by
      electron-phonon interaction through which an electron lead is coupled to a phonon
      lead if phonon-phonon coupling at the interface is very weak. We investigate the
      thermal conductance and rectification between the electron part and the phonon
      part using the nonequilibrium Green's function method. It is found that the
      thermal conductance has a nonmonotonic behavior as a function of average
      temperature or the coupling strength between the phonon leads in the metal part
      and the insulator part. The metal-insulator interface shows a clear thermal
      rectification effect, which can be reversed by a change in average temperature or
      the electron-phonon coupling.

PMID- 24131960
TI  - Theoretical investigation of porphyrin-based photosensitizers with enhanced NIR
      absorption.
AB  - Porphyrins are compounds which are fundamental for designing many
      photosensitizers assigned for use in photodynamic therapy (PDT). However,
      photosensitizers available on the drug market are not ideal for use in PDT among
      others because of their low absorption in the wavelength range optimal for tissue
      penetration, i.e. the near-infrared (NIR) spectral region. In the present study
      the density functional theory and its time dependent extension calculations have
      been used to design new porphyrin-based photosensitizers with absorption in the
      therapeutic window of PDT of 700-800 nm. Theoretical investigation of four
      different derivatives of the 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p
      THPP) revealed specific 'bridge' configurations which have a significant
      influence on absorption spectra. The results of the present study may be a useful
      starting point for future design of porphyrin derivatives as improved
      photosensitizers. 

PMID- 24131962
TI  - Endogenous 4beta-hydroxycholesterol-to-cholesterol ratio is not a validated
      biomarker for the assessment of CYP3A activity.

PMID- 24131963
TI  - Using social media to quantify nature-based tourism and recreation.
AB  - Scientists have traditionally studied recreation in nature by conducting surveys
      at entrances to major attractions such as national parks. This method is
      expensive and provides limited spatial and temporal coverage. A new source of
      information is available from online social media websites such as flickr. Here,
      we test whether this source of "big data" can be used to approximate visitation
      rates. We use the locations of photographs in flickr to estimate visitation rates
      at 836 recreational sites around the world, and use information from the profiles
      of the photographers to derive travelers' origins. We compare these estimates to
      empirical data at each site and conclude that the crowd-sourced information can
      indeed serve as a reliable proxy for empirical visitation rates. This new
      approach offers opportunities to understand which elements of nature attract
      people to locations around the globe, and whether changes in ecosystems will
      alter visitation rates.

PMID- 24131964
TI  - BRCAness: a deeper insight into basal-like breast tumors.
AB  - The molecular scenario of breast cancer has become more complex in the last few
      years. Distinguishing between BRCA-associated, sporadic, HER2-enriched and triple
      negative tumors is not sufficient to allow effective clinical management. Basal
      like breast cancer, a subtype of triple-negative breast cancer, differs from
      others grouped under this heading. Commonalities between BRCA-related tumors and
      basal-like breast cancers (BRCAness phenotype) are highly relevant to ongoing
      clinical trials, in particular those investigating targeted therapies (e.g. PARP
      inhibitors) in sporadic breast tumors. The 'gold standard' to identify basal-like
      phenotype is DNA microarray, but integrated results could provide a panel of
      biomarkers helpful in identifying 'BRCAness' tumors (e.g. copy number
      aberrations, abnormal protein localization and altered transcriptional levels)
      and other molecular targets, such as APE1,the inhibition of which is emerging as
      an attractive breast cancer treatment in certain therapeutic settings. 

PMID- 24131965
TI  - BRCA1- and BRCA2-related mutations: therapeutic implications in ovarian cancer.
AB  - Ovarian cancer is the deadliest among gynecologic cancers. Hereditary cancer
      related to BRCA1/2 gene mutations account for ~10%-12% of ovarian cancers. The
      BRCA1/2 proteins are important in homologous recombination (HR) repair of DNA.
      Patients with BRCA1/2 mutations have been reported to have improved
      chemosensitivity to platinum agents, longer disease-free intervals, and longer
      survivals than nonhereditary counterparts. Recent interest in poly(ADP-ribosyl)
      polymerase (PARP) proteins which are key components of base excision repair, has
      led to the development of PARP inhibitors; tumors arising in BRCA1/2 mutation
      carriers and/or with HR deficiency (HRD) are particularly sensitive to the action
      of these drugs. As 60%-80% of all advanced ovarian cancers are high-grade serous
      type, exhibiting HRD in at least 50% (referred as BRCAness) future antitumor
      strategies may depend on identifying these defects through molecular testing.
      Once HRD becomes amenable to routine testing, a larger group of ovarian cancer
      patients than are currently considered for PARP inhibitor trials, may benefit
      from such targeted therapy.

PMID- 24131967
TI  - Biomarkers and clinical interventions.

PMID- 24131966
TI  - Coming into focus: the nonovarian origins of ovarian cancer.
AB  - BACKGROUND: The traditional view of epithelial ovarian cancer asserts that all
      tumor subtypes share a common origin in the ovarian surface epithelium (OSE)
      DESIGN: A literature review was carried out to summarize the emerging
      understanding of extraovarian sources of epithelial ovarian carcinomas. RESULTS:
      Historically, there were no diagnostic criteria for documenting the origin of
      ovarian epithelial carcinomas. Moreover, there are no normal epithelial tissues
      in the ovary with morphologic similarities to these tumors. In fact, no precursor
      lesions have ever been reproducibly identified in the ovary. However, there is a
      strong correlation between extrauterine Mullerian tissue and the development of
      ovarian carcinomas, tumors of low malignant potential, and cystadenomas. The most
      recent support for this hypothesis comes from the careful analysis of risk
      reducing bilateral salpingo-oopherectomy specimens from BRCA1 or BRCA2 mutation
      carriers. These studies showed that a significant majority of high-grade serous
      ovarian carcinomas, the most common subtype, arise from the fallopian tube
      fimbriae rather than the OSE. CONCLUSIONS: Mounting evidence indicates that the
      vast majority of epithelial ovarian carcinomas are not ovarian in origin.
      Extrauterine Mullerian epithelium from various sites in the reproductive tract
      likely accounts for the diverse morphology and behavior of these tumors.

PMID- 24131968
TI  - Mammographic density, MRI background parenchymal enhancement and breast cancer
      risk.
AB  - Mammographic density (MD), representing connective and epithelial tissue
      (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an
      analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic
      microcalcification and parenchymal patterns as indicators of histologic "high
      risk" benign breast disease. Cancer 1990; 66: 1721-1725, Bartow SA, Pathak DR,
      Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and
      breast cancer risk factors. Am J Epidemiol 1995; 142: 813-819), MD was found to
      be strongly correlated with the collagen and epithelial content of the breast (Li
      T, Sun L, Miller N et al. The association of measured breast tissue
      characteristics with MD and other risk factors for breast cancer. Cancer
      Epidemiol Biomarkers Prev 2005; 14: 343-349), and another report showed that
      breast epithelium was highly concentrated in the areas of collagen concentration
      (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly
      increased concentration of breast epithelium but no increase in its proliferative
      activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming
      majority of the FGT, occupying an area on the slides obtained from the autopsy
      series some 15 times the area of glandular tissue. The relationship of MD with
      breast cancer risk appears likely to be due to a major extent to increasing
      epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic
      resonance imaging (breast MRI) and, as expected, it has been shown that this
      measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast
      MRI shows that normal FGT 'enhances' (background parenchymal enhancement, BPE)
      after contrast agent is administered(Morris EA. Diagnostic breast MR imaging:
      current status and future directions. Radiol Clin North Am 2007; 45: 863-880,
      vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of
      technique, image interpretation, diagnostic accuracy, and transfer to clinical
      practice. Radiology 2007; 244: 356-378), and a recent study suggests that BPE is
      also a major breast cancer risk factor, possibly as important as, and independent
      of MD (King V, Brooks JD, Bernstein JL et al. BPE at breast MR imaging and breast
      cancer risk. Radiology 2011; 260: 50-60). BPE is much more sensitive to the
      effects of menopause and tamoxifen than is FGT (King V, Gu Y, Kaplan JB et al.
      Impact of menopausal status on BPE and fibroglandular tissue on breast MRI. Eur
      Radiol 2012; 22: 2641-2647, King V, Kaplan J, Pike MC et al. Impact of tamoxifen
      on amount of fibroglandular tissue, BPE, and cysts on breast MRI. Breast J 2012;
      18: 527-534). Changes in MD and BPE may be most useful in predicting response to
      chemopreventive agents aimed at blocking breast cell proliferation. More study of
      the biological basis of the effects of MD and BPE is needed if we are to fully
      exploit these factors in developing chemopreventive approaches to breast cancer. 

PMID- 24131969
TI  - Acceptability of chemoprevention trials in high-risk subjects.
AB  - The development and current widespread acceptance of clinical trials is one of
      the major conceptual advances in research medicine introduced during the second
      half of the 20th century. Despite general agreement on the scientific merits of
      randomization, many patients and physicians are however reluctant to participate
      in randomized, controlled trials. If we focus on chemoprevention in healthy
      subjects, it is even more essential to evaluate the ethics, logistics, patient's
      and doctor's acceptability, acute and late toxic effect, patient accrual and
      compliance of treatment. Furthermore, the decision-making process about
      participating in a cancer chemoprevention trial is often poorly understood.
      Adherence to a cancer prevention trial requires in fact a strong sense of
      awareness and an ability to carefully assess risks and benefits. We review the
      main aspects in the chemo-preventive approach to patients at high risk for breast
      and ovarian cancer, focusing on different pharmacological risk reduction
      strategies, ongoing phase III chemoprevention studies in carriers of BRCA1/2
      germline mutation, the psychological and clinical factors implicated in decision
      making about a trial, and the possible impact of the trial design on the overall
      acceptability and adherence. 

PMID- 24131970
TI  - Alternatives to risk-reducing surgery for ovarian cancer.
AB  - BRCA1 and BRCA2 mutation carriers have an 18%-60% and 11%-27% lifetime risk of
      developing ovarian carcinoma, respectively. Prophylactic bilateral salpingo
      oophorectomy reduces the risk of this malignancy by up to 96%. Gynecological
      screening programs with periodical trans-vaginal ultrasound and serum CA125 assay
      have been widely used in women at hereditary high risk of ovarian carcinoma, but
      clinical results have been conflicting. These surveillance protocols have often
      fallen short of expectations because of the advanced stage of ovarian carcinoma
      in the identified screened women. Several investigations have been addressed to
      the detection of additional tumor markers able to generate more reliable
      screening tools. The combined serum assay of leptin, prolactin, osteopontin,
      CA125, macrophage inhibiting factor and insulin-like growth factor-II appears to
      have a significant better diagnostic reliability compared with serum CA125 alone
      in discriminating healthy individuals from ovarian carcinoma patients, and
      therefore, it could have a role in the screening of women at high risk for this
      malignancy. As far as chemoprevention is concerned, oral contraceptives
      significantly reduce the ovarian carcinoma risk also in BRCA mutation carriers,
      whereas the efficacy of fenretinide is still under investigation. 

PMID- 24131971
TI  - Local approaches to hereditary breast cancer.
AB  - The diagnostic and local treatment modalities of hereditary breast cancer (HBC)
      are evolving based on emerging evidence from new imaging, radiotherapy and
      surgical studies. The optimal selection of diagnostic and therapeutic strategies
      for the individual HBC patient remains an area of active research in this
      relatively new patient population. In this context, some rational pathways of
      intervention are currently available to both reduce cancer risk in mutation
      carriers without a cancer diagnosis, as well as to reduce the risk of recurrence
      or new cancers among the carriers already diagnosed with a malignancy. It is
      encouraging to notice to what degree certain interventions have successfully
      reduced both the risk of malignancy and the anxiety associated with this genetic
      diagnosis. This updated report aims at summarizing the most recent findings,
      while it identifies the areas of uncertainty that remain, and continue to present
      difficult challenges, particularly among younger HBC patients. 

PMID- 24131972
TI  - Introduction to epidemiology of breast and ovarian cancers.

PMID- 24131973
TI  - BRCA mutations and outcome in epithelial ovarian cancer (EOC): experience in
      ethnically diverse groups.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) patients with BRCA mutations have
      better prognosis than nonhereditary cases matched for histology and stage and age
      at diagnosis, especially Ashkenazi Jews (AJ). MATERIALS AND METHODS: We
      retrospectively reviewed data on 700 highly ethnically heterogeneous patients
      diagnosed with stage Ic-IV EOC and evaluated for BRCA status between 1995 and
      2009 in American, Israeli, and Italian medical centers. RESULTS: The ethnicities
      of the 190 patients (median age 55.5 years, range 31-83 years) were AJ, Jewish
      non-Ashkenazi, Caucasian, African-American, Hispanic, or unknown. Ninety were
      BRCA1/2 carriers (71 BRCA1 and 19BRCA2). The most common mutations in AJ and non
      AJ origins were 185delAG and 6174delT. Non-Jewish Caucasians exhibited the widest
      variation (>20 mutation subtypes). BRCA carriers had significantly prolonged
      median overall survival (93.6 months) compared with noncarriers (66.6 months; 95%
      confidence interval 44.5-91.7, P = 0.0081). There was no difference in
      progression-free survival. CONCLUSIONS: Our data demonstrate a wide variety of
      BRCA mutations in a highly ethnically diverse EOC population, and confirm that
      EOC BRCA mutation carriers have better prognosis with longer median survival than
      patients with nonhereditary disease. The contribution of unclassified BRCA
      variants to cancer etiology remains undetermined.

PMID- 24131974
TI  - Variants of unknown significance in BRCA testing: impact on risk perception,
      worry, prevention and counseling.
AB  - BACKGROUND: Sequence-based BRCA testing can identify variants of unknown
      significance (VUS). Relatively little is known about how well a test outcome of
      VUS is understood by patients and referring physicians, and whether genetic
      counselors have an interest in the development of VUS management guidelines.
      DESIGN: Self-administered questionnaires were completed by 36 VUS counselees, 75
      women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed
      24 genetic counselors and 22 referring family physicians. RESULTS: One-third of
      VUS failed to recall the clinical significance of their result. Incorrect recall
      was significantly higher among VUS with high-school-only education (70% versus
      19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk
      reducing surgeries among VUS counselees were more similar to NMF than to mutation
      carriers. Genetic counselors accurately predicted the difficulties counselees
      would have with a VUS result and identified the need for VUS management
      guidelines. Referring physicians unanimously stated that genetic testing was
      indicated for unaffected siblings of VUS carriers. CONCLUSIONS: While VUS seems
      to be correctly perceived by counselees as more similar to NMF than to a
      pathogenic mutation, miscomprehension of VUS is more common, particularly in
      counselees with lower education. VUS-related educational interventions for both
      VUS counselees and their referring physicians are needed. We encourage the
      development of national VUS-related guidelines for genetic counselors.

PMID- 24131975
TI  - Biology of hereditary breast and ovarian cancers.

PMID- 24131976
TI  - Male breast cancer: genetics, epigenetics, and ethical aspects.
AB  - BACKGROUND AND STUDY DESIGN: Male breast cancer (MBC) is a rare disease compared
      with female BC and our current understanding regarding breast carcinogenesis in
      men has been largely extrapolated from the female counterpart. We focus on
      differences between the ethical issues related to male and female BC patients. A
      systematic literature search by using PubMed
      (http://www.ncbi.nlm.nih.gov/pubmed/), was carried out to provide a synopsis of
      the current research in the field of MBC genetics, epigenetics and ethics.
      Original articles and reviews published up to September 2012 were selected by
      using the following search key words to query the PubMed website: 'male breast
      cancer', 'male breast cancer and genetic susceptibility', 'male breast cancer and
      epigenetics', 'male breast cancer and methylation', 'male breast cancer and
      miRNA', 'male breast cancer and ethics'. RESULTS AND CONCLUSIONS: As in women,
      three classes of breast cancer genetic susceptibility (high, moderate, and low
      penetrance) are recognized in men. However, genes involved and their impact do
      not exactly overlap in female and male BC. Epigenetic alterations are currently
      scarcely investigated in MBC, however, the different methylation and miRNA
      expression profiles identified to date in female and male BCs suggest a potential
      role for epigenetic alterations as diagnostic biomarkers. Overall, much still
      needs to be learned about MBC and, because of its rarity, the main effort is to
      develop large consortia for moving forward in understanding MBC and improving the
      management of MBC patients on a perspective of gender medicine.

PMID- 24131977
TI  - Breast cancer risk in BRCA1 mutation carriers: insight from mouse models.
AB  - Since its identification 20 years ago, the biological basis for the high breast
      cancer risk in women who have germline BRCA1 mutations has been an area of
      intense study for three reasons. First, BRCA1 was the first gene shown to
      associate with breast cancer risk, and therefore serves as model for
      understanding genetic susceptibility. Second, the type of breast cancer that
      occurs in these women has specific features that have engendered new hypotheses
      about the cancer biology. Third, it is hoped that understanding the origins of
      this disease may provide the means to prevent disease. Resolving this question
      has proven extremely challenging because the biology controlled by BRCA1 is
      complex. Our working model is that the high frequency of basal-like breast cancer
      in BRCA1 mutation carriers is the result of a self-perpetuating triad of cellular
      phenotypes consisting of: (i) intrinsic defects in DNA repair and centrosome
      regulation that lead to genomic instability and increases spontaneous
      transformation; (ii) aberrant lineage commitment; and (iii) increased
      proliferation due to in large part to increased IGF-1 activity. We propose that
      the last is key and is a potential entree for preventing breast cancer in BRCA1
      mutation carriers. 

PMID- 24131978
TI  - Hereditary ovarian and breast cancer: what have we learned?
AB  - An autosomal-dominant inherited trait predisposing women to both breast cancer
      (BC) and ovarian cancer (OC) was first described in 1971. Subsequent strides were
      made in identifying mutations in the eventually cloned genes BRCA1 and BRCA2 as
      being responsible for hereditary BC and OC (HBOC) in many women with early-onset
      HBOC. More recently, modifiers of BC risk have also been identified and are under
      study. The biological and molecular genetic pathways for malignant transformation
      in OC (ovarian epithelium and/or epithelium of the fallopian tube or, possibly,
      the endometrium and endocervix) remain elusive. The answer to the question 'What
      have we learned?' which is part of our chapter title unfortunately remains
      incomplete. However, intensive worldwide research indicates that its malignant
      transformation is the product of a multi-step process where there is an array of
      mutations which account for three or more classes of genes, inclusive of proto
      oncogenes, tumor suppressor genes and mutator genes. This causal uncertainty
      heralds an enormous clinical-pathology dilemma, given the fact that epithelial
      OC, together with related Mullerian duct carcinoma, harbor the highest fatality
      rates of all gynecologic malignancies. 

PMID- 24131979
TI  - Minimal piggyBac vectors for chromatin integration.
AB  - We describe novel transposon piggyBac vectors engineered to deliver transgenes as
      efficiently as currently available piggyBac systems, but with significantly less
      helper DNA co-delivered into the host genome. To generate these plasmids, we
      identified a previously unreported aspect of transposon biology, that the full
      length terminal domains required for successful plasmid-to-chromatin transgene
      delivery can be removed from the transgene delivery cassette to other parts of
      the plasmid without significantly impairing transposition efficiency. This is
      achieved by including in the same plasmid, an additional helper piggyBac sequence
      that contains both long terminal domains, but is modified to prevent its
      transposition into the host genome. This design decreases the size of the
      required terminal domains within the delivered gene cassette of the piggyBac
      vector from about 1500 to just 98 base pairs. By removing these sequences from
      the delivered gene cassette, they are no longer incorporated into the host genome
      which may reduce the risk of target cell transformation. 

PMID- 24131980
TI  - Liver-directed adeno-associated virus serotype 8 gene transfer rescues a lethal
      murine model of citrullinemia type 1.
AB  - Citrullinemia type 1 (CTLN1) is an autosomal recessive disorder of metabolism
      caused by a deficiency of argininosuccinate synthetase. Despite optimal
      management, CTLN1 patients still suffer from lethal metabolic instability and
      experience life-threatening episodes of acute hyperammonemia. A murine model of
      CTLN1 (fold/fold) that displays lethality within the first 21 days of life was
      used to determine the efficacy of adeno-associated viral (AAV) gene transfer as a
      potential therapy. An AAV serotype 8 (AAV8) vector was engineered to express the
      human ASS1 cDNA under the control of a liver-specific promoter (thyroxine-binding
      globulin, TBG), AAV8-TBG-hASS1, and delivered to 7-10 days old mice via
      intraperitoneal injection. Greater than 95% of the mice were rescued from
      lethality and survival was extended beyond 100 days after receiving a single dose
      of vector. AAV8-TBG-hASS1 treatment resulted in liver-specific expression of
      hASS1, increased ASS1 enzyme activity, reduction in plasma ammonia and citrulline
      concentrations and significant phenotypic improvement of the fold/fold growth and
      skin phenotypes. These experiments highlight a gene transfer approach using AAV8
      vector for liver-targeted gene therapy that could serve as a treatment for CTLN1.

PMID- 24131981
TI  - Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction
      of the dog brain.
AB  - Canine models have many advantages for evaluating therapy of human central
      nervous system (CNS) diseases. In contrast to nonhuman primate models, naturally
      occurring canine CNS diseases are common. In contrast to murine models, the dog's
      lifespan is long, its brain is large and the diseases affecting it commonly have
      the same molecular, pathological and clinical phenotype as the human diseases. We
      compared the ability of four intracerebrally injected adeno-associated virus
      vector (AAV) serotypes to transduce the dog brain with green fluorescent protein
      as the first step in using these vectors to evaluate both delivery and efficacy
      in naturally occurring canine homologs of human diseases. Quantitative measures
      of transduction, maximum diameter and area, identified both AAV2/9 and AAV2/rh10
      as significantly more efficient than either AAV2/1 or AAV2/5 at transducing
      cerebral cortex, caudate nucleus, thalamus and internal capsule. Fluorescence co
      labeling with cell-type-specific antibodies demonstrated that AAV2/9 and
      AAV2/rh10 were capable of primarily transducing neurons, although glial
      transduction was also identified and found to be more efficient with the AAV2/9
      vector. These data are a prerequisite to evaluating the efficacy of recombinant
      AAV vectors carrying disease-modifying transgenes to treat naturally occurring
      canine models in preclinical studies of human CNS disease therapy. 

PMID- 24131982
TI  - Pluronic-PEI copolymers enhance exon-skipping of 2'-O-methyl phosphorothioate
      oligonucleotide in cell culture and dystrophic mdx mice.
AB  - A series of small-size polyethylenimine (PEI)-conjugated pluronic polycarbamates
      (PCMs) have been investigated for the ability to modulate the delivery of 2'-O
      methyl phosphorothioate RNA (2'-OMePS) in vitro and in dystrophic mdx mice. The
      PCMs retain strong binding capacity to negatively charged oligomer as
      demonstrated by agarose gel retardation assay, with the formation of condensed
      polymer/oligomer complexes at a wide-range weight ratio from 1:1 to 20:1. The
      condensed polymer/oligomer complexes form 100-300 nm nanoparticles. Exon-skipping
      effect of 2'-OMePS was dramatically enhanced with the use of the most effective
      PCMs in comparison with 2'-OMePS alone in both cell culture and in vivo,
      respectively. More importantly, the effective PCMs, especially those composed of
      moderate size (2k-5kDa) and intermediate hydrophilic-lipophilic balance (7-23) of
      pluronics, enhanced exon-skipping of 2'-OMePS with low toxicity as compared with
      Lipofectamine-2000 in vitro or PEI 25k in vivo. The variability of individual PCM
      for delivery of antisense oligomer and plasmid DNA indicate the complexity of
      interaction between polymer and their cargos. Our data demonstrate the potential
      of PCMs to mediate delivery of modified antisense oligonucleotides to the muscle
      for treating muscular dystrophy or other appropriate myodegenerative diseases. 

PMID- 24131984
TI  - The Kramers-Kronig relations for usual and anomalous Poisson-Nernst-Planck
      models.
AB  - The consistency of the frequency response predicted by a class of electrochemical
      impedance expressions is analytically checked by invoking the Kramers-Kronig (KK)
      relations. These expressions are obtained in the context of Poisson-Nernst-Planck
      usual or anomalous diffusional models that satisfy Poisson's equation in a finite
      length situation. The theoretical results, besides being successful in
      interpreting experimental data, are also shown to obey the KK relations when
      these relations are modified accordingly. 

PMID- 24131983
TI  - Molecular mechanism of strigolactone perception by DWARF14.
AB  - Strigolactones (SLs) are phytohormones that inhibit shoot branching and function
      in the rhizospheric communication with symbiotic fungi and parasitic weeds. An
      alpha/beta-hydrolase protein, DWARF14 (D14), has been recognized to be an
      essential component of plant SL signalling, although its precise function remains
      unknown. Here we present the SL-dependent interaction of D14 with a gibberellin
      signalling repressor SLR1 and a possible mechanism of phytohormone perception in
      D14-mediated SL signalling. D14 functions as a cleavage enzyme of SLs, and the
      cleavage reaction induces the interaction with SLR1. The crystal structure of D14
      shows that 5-hydroxy-3-methylbutenolide (D-OH), which is a reaction product of
      SLs, is trapped in the catalytic cavity of D14 to form an altered surface. The
      D14 residues recognizing D-OH are critical for the SL-dependent D14-SLR1
      interaction. These results provide new insight into crosstalk between gibberellin
      and SL signalling pathways. 

PMID- 24131985
TI  - Expression levels of the innate response gene RIG-I and its regulators RNF125 and
      TRIM25 in HIV-1-infected adult and pediatric individuals.
AB  - OBJECTIVE: TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate
      innate immune responses by detecting microorganism invasion. RIG-I activation
      results in the production of interferon (IFN) type 1 and IFN responsive genes
      (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG
      I function, our aim was to assess whether the levels of these three genes vary
      between healthy and HIV-infected individuals and whether these levels are related
      to disease progression. DESIGN: Gene expression analyses for RIG-I, RNF125, and
      TRIM25 were performed for HIV-infected adults and the children's peripheral blood
      mononuclear cells (PBMCs). METHODS: Reverse transcription-quantitative PCRs (RT
      qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125
      and TRIM25 from PBMCs purified from control or HIV-infected individuals. RESULTS:
      Controls express higher levels of the three genes when compared to HIV-infected
      patients. These expressions are clearly distinct between healthy and progressors,
      and are reproduced in adults and children. In controls, RNF125 is the highest
      expressed gene, whereas in progressors, RIG-I is either the highest expressed
      gene or is expressed similarly to RNF125 and TRIM25. CONCLUSION: A pattern of
      expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The
      high expression of RNF125 in healthy individuals reflects the importance of
      keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent
      with this assumption, RNF125 levels are lower in HIV patients and importantly,
      the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results
      might help to predict disease progression and unveil the role of poorly
      characterized host genes during HIV infection.

PMID- 24131986
TI  - Borata-alkene derivatives conveniently made by frustrated Lewis pair chemistry.
AB  - Two (aryl)PXY starting materials (aryl = mesityl or 2,4,6-triisopropylphenyl; X,Y
      = Cl, Br) were reacted with lithiated conjugated enynes (derived from 2
      methylbutenyne or 1-ethynylcyclohexene) to yield the respective
      (aryl)bis(enynyl)phosphanes. Their reaction with HB(C6F5)2 gave the heterocyclic
      five-membered zwitterionic borata-diene compounds containing the aryl group and
      one unchanged enynyl substituent at phosphorus. The borata-alkene products were
      thought to arise from a two step process of regioselective alkyne hydroboration
      followed by an internal phosphane attack on the boryldiene unit. Three examples
      of the ring-closed borata-alkene type products were characterized by X-ray
      diffraction. 

PMID- 24131987
TI  - Competitive hydrosilylation in carbon nanoreactors: probing the effect of
      nanoscale confinement on selectivity.
AB  - Platinum nanoparticles (PtNP) either imbedded within (PtNP@GNF) or adsorbed on
      the surface (PtNP/GNF) of hollow graphitised carbon nanofibres catalyse
      hydrosilylation reactions inside or outside the nanoreactor respectively.
      Comparison of the products formed using PtNP@GNF and PtNP/GNF reveals that
      nanoreactors create an environment promoting the formation of aromatic over
      aliphatic products in the competitive hydrosilylation of phenylacetylene with a
      mixture of triethylsilane and dimethylphenylsilane reactants. Quantification of
      the distribution of reaction products indicates a three- to four-fold increase in
      the concentration of aromatic reactants within GNF depending on the dimensions of
      the carbon nanoreactor. The altered local concentrations of reactants in PtNP@GNF
      combined with stabilisation of the reaction intermediates by interactions with
      the nanoreactor interior cause significant changes in the pathways of chemical
      transformations. The effects of nanoscale confinement on the reactivity of
      molecules can be harnessed for preparative synthesis in carbon nanoreactors. 

PMID- 24131988
TI  - Possible association of Kingella kingae with infantile spondylodiscitis.
AB  - The course of the spondylodiscitis' infantile form is characterized by a mild-to
      moderate clinical and biologic inflammatory response. Unfortunately, blood and
      disk/vertebral aspiration cultures show a high percentage of negative results.
      However, detecting Kingella kingae DNA in the oropharynx provided reasonable
      suspicion, to our opinion, that this microorganism is responsible for the
      spondylodiscitis. 

PMID- 24131993
TI  - Sharply autofocused ring-Airy beams transforming into non-linear intense light
      bullets.
AB  - Controlling the propagation of intense optical wavepackets in transparent media
      is not a trivial task. During propagation, low- and high-order non-linear
      effects, including the Kerr effect, multiphoton absorption and ionization, lead
      to an uncontrolled complex reshaping of the optical wavepacket that involves
      pulse splitting, refocusing cycles in space and significant variations of the
      focus. Here we demonstrate both numerically and experimentally that intense,
      abruptly autofocusing beams in the form of accelerating ring-Airy beams are able
      to reshape into non-linear intense light-bullet wavepackets propagating over
      extended distances, while their positioning in space is extremely well defined.
      These unique wavepackets can offer significant advantages in numerous fields such
      as the generation of high harmonics and attosecond physics or the precise micro
      engineering of materials. 

PMID- 24131994
TI  - Group 5 hydride and borohydride complexes supported by cyclopentadienyl-imido
      ligand sets.
AB  - Reactions of Cp*Ta(NAr)Cl2 and CpM(NAr)Cl2 (M = Nb, Ta; Ar = 2,6-C6H3(i)Pr2) with
      NaBH4 in the presence of an excess of PMe3 provided facile access to the
      corresponding dihydride derivatives Cp(R)M(NAr)H2(PMe3) (Cp(R) = Cp, Cp*).
      Reaction of Cp*Nb(NAr)Cl2 with NaBH4 in the absence of phosphine gave the Nb(+5)
      borohydride-hydride complex Cp*Nb(NAr)H(eta(2)-BH4). When the corresponding
      reactions for CpM(NAr)Cl2 (M = Nb, Ta) were carried out in the absence of an
      excess of phosphine, dimeric M(IV) products [CpM(MU-NAr)(eta(2)-BH4)]2 containing
      M-M single bonds were formed. 

PMID- 24131995
TI  - Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased
      glycogen levels, mTOR activation, and autophagy defects in Lafora disease.
AB  - Lafora disease (LD), a fatal genetic form of myoclonic epilepsy, is characterized
      by abnormally high levels of cellular glycogen and its accumulation as Lafora
      bodies in affected tissues. Therefore the two defective proteins in LD-laforin
      phosphatase and malin ubiquitin ligase-are believed to be involved in glycogen
      metabolism. We earlier demonstrated that laforin and malin negatively regulate
      cellular glucose uptake by preventing plasma membrane targeting of glucose
      transporters. We show here that loss of laforin results in activation of
      serum/glucocorticoid-induced kinase 1 (SGK1) in cellular and animals models and
      that inhibition of SGK1 in laforin-deficient cells reduces the level of plasma
      membrane-bound glucose transporter, glucose uptake, and the consequent glycogen
      accumulation. We also provide evidence to suggest that mammalian target of
      rapamycin (mTOR) activates SGK1 kinase in laforin-deficient cells. The mTOR
      activation appears to be a glucose-dependent event, and overexpression of
      dominant-negative SGK1 suppresses mTOR activation, suggesting the existence of a
      feedforward loop between SGK1 and mTOR. Our findings indicate that inhibition of
      SGK1 activity could be an effective therapeutic approach to suppress glycogen
      accumulation, inhibit mTOR activity, and rescue autophagy defects in LD. 

PMID- 24131998
TI  - Enhanced photoresponse in curled graphene ribbons.
AB  - Graphene has become one of the most promising materials for future
      optoelectronics due to its ultrahigh charge-carrier mobility, high light
      transmission, and universal absorbance in the near-infrared and visible spectral
      ranges. However, a zero band gap and ultrafast recombination of the photoexcited
      electron-hole pairs limit graphene's potential in photovoltaic generation. Recent
      studies have shown that hot carriers can enhance photovoltaic generation in
      graphene p-n junctions through the photothermoelectric effect (PTE). It is,
      therefore, desirable to synthesize graphene nanostructures with an intrinsic PTE
      induced photocurrent response. Here we report a simple method to synthesize quasi
      one dimensional (quasi-1D) curled graphene ribbons (CGRs) that generate a
      photocurrent response with two orders of magnitude enhancement. Scanning
      photocurrent and photoluminescence measurements reveal that the photocurrent
      response is primarily attributed to the PTE and that the infrared emission may
      arise from thermal radiation. These results offer a new way to fabricate graphene
      based optoelectronics with an enhanced photoresponse. 

PMID- 24131996
TI  - Specific deletion of Cdc42 does not affect meiotic spindle organization/migration
      and homologous chromosome segregation but disrupts polarity establishment and
      cytokinesis in mouse oocytes.
AB  - Mammalian oocyte maturation is distinguished by highly asymmetric meiotic
      divisions during which a haploid female gamete is produced and almost all the
      cytoplasm is maintained in the egg for embryo development. Actin-dependent
      meiosis I spindle positioning to the cortex induces the formation of a polarized
      actin cap and oocyte polarity, and it determines asymmetric divisions resulting
      in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic
      maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional
      knockout technology. We find that Cdc42 deletion causes female infertility in
      mice. Cdc42 deletion has little effect on meiotic spindle organization and
      migration to the cortex but inhibits polar body emission, although homologous
      chromosome segregation occurs. The failure of cytokinesis is due to the loss of
      polarized Arp2/3 accumulation and actin cap formation; thus the defective
      contract ring. In addition, we correlate active Cdc42 dynamics with its function
      during polar body emission and find a relationship between Cdc42 and polarity, as
      well as polar body emission, in mouse oocytes. 

PMID- 24131997
TI  - Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to
      specific membrane sites.
AB  - Src interactions with the plasma membrane are an important determinant of its
      activity. In turn, Src activity modulates its association with the membrane
      through binding of activated Src to phosphotyrosylated proteins. Caveolin-1 (Cav
      1), a major component of caveolae, is a known Src phosphorylation target, and
      both were reported to regulate cell transformation. However, the nature of Src
      Cav-1 interactions, a potential mechanism of their coregulation, remained
      unclear. Here we used fluorescence recovery after photobleaching beam-size
      analysis, coimmunoprecipitation, quantitative imaging, and far-Western studies
      with cells expressing wild type, as well as structural and activity mutants of
      Src-green fluorescent protein and Cav-1-monomeric red fluorescent protein, to
      measure their interactions with the membrane and with each other. We show dynamic
      Src-plasma membrane interactions, which are augmented and stabilized by Cav-1.
      The mechanism involves phosphorylation of Cav-1 at Tyr-14 by Src and subsequent
      binding of the Src SH2 domain to phospho-Cav-1, leading to accumulation of
      activated Src in focal adhesions. This novel Cav-1 function potentially modulates
      focal adhesion dynamics. 

PMID- 24131999
TI  - Distinct genetic clades of Malaysian Copera damselflies and the phylogeny of
      platycnemine subfamilies.
AB  - The phylogenetic relationships of some taxa in the Platycnemidinae at the species
      and generic levels have been investigated. Phylogenetic trees were generated from
      both individual mitochondrial encoded COI, COII, 16S rDNA and nuclear encoded 28S
      rDNA and also combined sequences; these data indicate that the component taxa of
      the genus Copera belong to two distinct genetic clades - the marginipes group and
      the annulata group. There was no distinct genetic difference between the red
      legged and yellow-legged morphs of C. vittata. Molecular data showed that the
      annulata group is considered a member of the genus Platycnemis, as originally
      proposed. The genus Coeliccia, a member of the subfamily Calicnemiinae
      (Platycnemididae), is not grouped with the Platycnemidinae. The Disparoneurinae
      of the 'Protoneuridae' showed a closer relationship to the Platycnemidinae than
      the Calicnemiinae. The dataset supports the placement of the Disparoneurinae as a
      subfamily of the Platycnemididae. This resolves the monophyly of Platycnemididae.

PMID- 24132000
TI  - Understanding the joint effects of EBV and vitamin D in MS.

PMID- 24132001
TI  - One can prevent post-partum MS relapses by exclusive breast feeding: no.

PMID- 24132002
TI  - One can prevent post-partum MS relapses by exclusive breast feeding: yes.

PMID- 24132003
TI  - One can prevent post-partum MS relapses by exclusive breast feeding: commentary.

PMID- 24132004
TI  - Diabetes insipidus as a rare cause of acute cognitive impairment in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a
      diversity of clinical symptoms including palsy and cognitive impairment. We
      present a 59-year-old woman with a history of secondary progressive MS since
      1987, who was referred to our department because of recent onset of confusion and
      polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low
      urine osmolality. Under water deprivation, diuresis and low urine osmolality
      persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin
      resulted in normalisation of serum sodium as well as urine osmolarity, confirming
      a diagnosis of central diabetes insipidus. As drug-induced diabetes could be
      excluded, pituitary magnetic resonance imaging (MRI) was performed. A
      demyelinating lesion was detected in the hypothalamus. The patient was started on
      oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels
      have since remained normal. In summary, we report the rare case of a patient
      presenting with diabetes insipidus due to progressive MS. Diabetes insipidus
      should be considered in MS patients who develop new onset of polydipsia. 

PMID- 24132005
TI  - Separation of bones from chest radiographs by means of anatomically specific
      multiple massive-training ANNs combined with total variation minimization
      smoothing.
AB  - Most lung nodules that are missed by radiologists as well as computer-aided
      detection (CADe) schemes overlap with ribs or clavicles in chest radiographs
      (CXRs). The purpose of this study was to separate bony structures such as ribs
      and clavicles from soft tissue in CXRs. To achieve this, we developed
      anatomically specific multiple massive-training artificial neural networks
      (MTANNs) combined with total variation (TV) minimization smoothing and a
      histogram-matching-based consistency improvement method. The anatomically
      specific multiple MTANNs were designed to separate bones from soft tissue in
      different anatomic segments of the lungs. Each of the MTANNs was trained with the
      corresponding anatomic segment in the teaching bone images. The output segmental
      images from the multiple MTANNs were merged to produce an entire bone image. TV
      minimization smoothing was applied to the bone image for reduction of noise while
      preserving edges. This bone image was then subtracted from the original CXR to
      produce a soft-tissue image where bones were separated out. This new method was
      compared with conventional MTANNs with a database of 110 CXRs with nodules. Our
      new anatomically specific MTANNs separated rib edges, ribs close to the lung
      wall, and the clavicles from soft tissue in CXRs to a substantially higher level
      than did the conventional MTANNs, while the conspicuity of lung nodules and
      vessels was maintained. Thus, our technique for bone-soft-tissue separation by
      means of our new MTANNs would be potentially useful for radiologists as well as
      CADe schemes in detection of lung nodules on CXRs. 

PMID- 24132006
TI  - Traveling wave magnetic particle imaging.
AB  - Most 3-D magnetic particle imaging (MPI) scanners currently use permanent magnets
      to create the strong gradient field required for high resolution MPI. However,
      using permanent magnets limits the field of view (FOV) due to the large amount of
      energy required to move the field free point (FFP) from the center of the
      scanner. To address this issue, an alternative approach called "Traveling Wave
      MPI" is here presented. This approach employs a novel gradient system, the
      dynamic linear gradient array, to cover a large FOV while dynamically creating a
      strong magnetic gradient. The proposed design also enables the use of a so-called
      line-scanning mode, which simplifies the FFP trajectory to a linear path through
      the 3-D volume. This results in simplified mathematics, which facilitates the
      image reconstruction. 

PMID- 24132007
TI  - Quantitative comparison of reconstruction methods for intra-voxel fiber recovery
      from diffusion MRI.
AB  - Validation is arguably the bottleneck in the diffusion magnetic resonance imaging
      (MRI) community. This paper evaluates and compares 20 algorithms for recovering
      the local intra-voxel fiber structure from diffusion MRI data and is based on the
      results of the "HARDI reconstruction challenge" organized in the context of the
      "ISBI 2012" conference. Evaluated methods encompass a mixture of classical
      techniques well known in the literature such as diffusion tensor, Q-Ball and
      diffusion spectrum imaging, algorithms inspired by the recent theory of
      compressed sensing and also brand new approaches proposed for the first time at
      this contest. To quantitatively compare the methods under controlled conditions,
      two datasets with known ground-truth were synthetically generated and two main
      criteria were used to evaluate the quality of the reconstructions in every voxel:
      correct assessment of the number of fiber populations and angular accuracy in
      their orientation. This comparative study investigates the behavior of every
      algorithm with varying experimental conditions and highlights strengths and
      weaknesses of each approach. This information can be useful not only for
      enhancing current algorithms and develop the next generation of reconstruction
      methods, but also to assist physicians in the choice of the most adequate
      technique for their studies. 

PMID- 24132008
TI  - Automatic generation of statistical pose and shape models for articulated joints.
AB  - Statistical analysis of motion patterns of body joints is potentially useful for
      detecting and quantifying pathologies. However, building a statistical motion
      model across different subjects remains a challenging task, especially for a
      complex joint like the wrist. We present a novel framework for simultaneous
      registration and segmentation of multiple 3-D (CT or MR) volumes of different
      subjects at various articulated positions. The framework starts with a pose model
      generated from 3-D volumes captured at different articulated positions of a
      single subject (template). This initial pose model is used to register the
      template volume to image volumes from new subjects. During this process, the Grow
      Cut algorithm is used in an iterative refinement of the segmentation of the bone
      along with the pose parameters. As each new subject is registered and segmented,
      the pose model is updated, improving the accuracy of successive registrations. We
      applied the algorithm to CT images of the wrist from 25 subjects, each at five
      different wrist positions and demonstrated that it performed robustly and
      accurately. More importantly, the resulting segmentations allowed a statistical
      pose model of the carpal bones to be generated automatically without interaction.
      The evaluation results show that our proposed framework achieved accurate
      registration with an average mean target registration error of 0.34 +/-0.27 mm.
      The automatic segmentation results also show high consistency with the ground
      truth obtained semi-automatically. Furthermore, we demonstrated the capability of
      the resulting statistical pose and shape models by using them to generate a
      measurement tool for scaphoid-lunate dissociation diagnosis, which achieved 90%
      sensitivity and specificity. 

PMID- 24132009
TI  - Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L
      NAME hypertensive rats.
AB  - The cardiovascular effects and pharmacokinetics of nebivolol were assessed in
      N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control
      rats. Male Wistar rats were randomly divided to drink tap water (control) or L
      NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg(-1) i.v.) on
      blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L
      NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d.
      and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was
      studied by means of traditional blood sampling. Nebivolol showed enantioselective
      pharmacokinetics in both experimental groups; the clearance and the volume of
      distribution of l-nebivolol were significantly greater than those of the d
      enantiomer. The hypotensive response to nebivolol was significantly enhanced in L
      NAME rats (Deltamean arterial pressure (MAP): -16.1+/-1.1%, P<0.05 vs. control
      rats) compared with normotensive animals (DeltaMAP: -1.4+/-2.1%). An analysis of
      the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare
      with the control rats. Nebivolol significantly reduced the low-frequency/high
      frequency ratio in hypertensive L-NAME animals compared with normotensive rats.
      Short-term BPV was markedly reduced by nebivolol in both experimental groups,
      although the attenuation of the s.d. of BP recording was greater in L-NAME rats.
      In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in
      L-NAME rats compared with normotensive animals, which is most likely due to a
      greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated
      short-term BPV in both experimental groups, suggesting that beta-blockers with
      additional pharmacological actions provide beneficial cardiovascular effects by
      controlling high BP and its short-term variability. 

PMID- 24132010
TI  - Biological, electrical and echocardiographic indices versus cardiac magnetic
      resonance imaging in diagnosing left ventricular hypertrophy.
AB  - The aim of this study was to compare the diagnostic performance of N-terminal pro
      brain natriuretic peptide (NT-proBNP), electrocardiographic (ECG) criteria and
      transthoracic echocardiography (TTE) versus cardiac magnetic resonance imaging in
      detecting left ventricular hypertrophy (LVH). The study included 42 hypertensive
      subjects with mean+/-s.d. age 48.1+/-12.3 years, 57.1% men, 24-h ambulatory blood
      pressure 144/89 mm Hg, left ventricular ejection fraction >50%, without symptoms
      of heart failure, and not taking any drugs that interfere with hormonal
      regulation. The accuracies of the methods in detecting LVH were compared at two
      diagnostic LVH cutoffs: low, 83 g m(-2) in men and 67 g m(-2) in women; and high,
      96 g m(-2) in men and 81 g m(-2) in women. With the low and high LVH cutoffs, the
      areas under the receiver-operating characteristic curves and the optimal values
      for NT-proBNP were 0.761, 0.849, 200 and 421 pg ml(-1), respectively. An NT
      proBNP level under 30 pg ml(-1) ruled out LVH with 100% sensitivity. The optimal
      values and literature-based values of NT-proBNP allowed a correct classification
      of 73-81% of the subjects. In 80-90% of the cases, the diagnostic accuracy of NT
      proBNP was close to that of ECG criteria but lower than that of TTE criteria.
      Interestingly, combining ECG criteria and NT-proBNP level improved the diagnostic
      performance to be at least comparable to that of TTE: the percentages of
      correctly classified subjects were 73-95% vs. 67-86%, respectively. Of note, the
      range considers both diagnostic LVH cutoffs. The simultaneous use of ECG criteria
      and NT-proBNP plasma levels seemed to be powerful enough to detect LVH in most
      hypertensive subjects.

PMID- 24132011
TI  - Detecting diabetic risk using the oral glucose tolerance test in Chinese patients
      with hypertension: a cross-sectional study.
AB  - To analyze the clinical significance of the oral glucose tolerance test (OGTT) in
      the assessment of abnormal glucose metabolism in Chinese patients with
      hypertension. In this cross-sectional study of 10,173 hypertensive adult patients
      from eight sites in China, data on patient, clinical and disease characteristics
      were collected, and fasting plasma glucose (FPG) levels were measured. A subset
      of 5322 patients also underwent an OGTT. Abnormal glucose metabolism (impaired
      glucose regulation (IGR) or diabetes mellitus (DM)) was detected in 31.1% of the
      10,173 patients by FPG testing and in 67% of the 5322 patients by OGTT. OGTT
      increased the detection rate by 35.8%. Patients with FPG levels >=5.6 and >=6.1
      mmol l(-1) had the mean OGTT 2-h plasma glucose levels of 8.79 and 9.68 mmol l(
      1), respectively. Compared with normoglycemic patients, those with IGR or DM had
      higher rates of total proteinuria (normoglycemic 15.8% vs. IGR 22.1% vs. DM
      33.7%, P<0.001), a lower absolute estimated glomerular filtration rate (eGFR; in
      ml min(-1) per 1.73 m(2)) (82.9 vs. 80.77 vs. 79.74, P=0.06) and a higher
      prevalence of cardiovascular disease (normoglycemic 17.6% vs. IGR/DM 13.8%,
      P<0.001). Abnormal abdominal circumference, eGFR <=60 ml min(-1) per 1.73 m(2),
      and proteinuria were independently associated with abnormal glucose metabolism
      (IGR or DM). Hypertensive patients who are diabetic or at risk of diabetes are at
      greater risk of renal damage and cardiovascular disease than those who are
      normoglycemic. It is insufficient to assess the glucose metabolism status of
      Chinese hypertensive patients using only FPG testing; the use of OGTT can
      increase the detection rate by 35.8%. Patients whose FPG levels were <5.6 mmol l(
      1) may be found to have abnormal glucose metabolism after an OGTT.

PMID- 24132012
TI  - The effects of exposure to general anesthesia in infancy on academic performance
      at age 12.
AB  - BACKGROUND: Recent evidence from juvenile animal models has shown that exposure
      to anesthetic drugs above threshold doses during a critical neurodevelopmental
      window causes widespread neuronal apoptosis, resulting in irreversible brain
      damage and subsequent learning difficulties. The relevance of this to human
      infants having general anesthesia for minor surgery is unknown. In this pilot
      observational cohort study, we sought to determine whether children exposed to
      general anesthesia for minor surgery during infancy exhibited differences in
      academic achievement at age 12 years, as evidenced by (1) lower aggregate scores
      in the Singapore standardized Primary School Leaving Examination (PSLE) and (2)
      formally diagnosed learning disability, compared with children who were never
      exposed to anesthesia or sedation. METHODS: We compared 100 full-term, apparently
      healthy children aged 12 years who were exposed to general anesthesia for minor
      surgery before age 1 at our institution with an age-matched cohort of 106
      children who were never exposed to anesthesia or sedation. Parents of children
      completed a 20-minute telephone interview with questions regarding their
      children's medical history, school environment, and home environment. RESULTS:
      The difference in mean PSLE aggregate scores (3.0; 95% confidence interval [CI], 
      8.3 to 14.3) between exposed (197.0; 95% CI, 185.6-208.4) and control groups
      (194.0; 95% CI, 182.9-205.1) was not statistically significant (P = 0.603). The
      presence of formally diagnosed learning disability was 15% (15 of 100) in the
      exposed group compared with 3.77% (4 of 106) in the control group (P < 0.001).
      The odds ratio for a formal diagnosis of learning disability in those exposed to
      general anesthesia relative to controls was 4.5 (95% CI, 1.44-14.1). CONCLUSION:
      The odds of a formal diagnosis of learning disability by age 12 years in
      apparently healthy children exposed to general anesthesia for minor surgery
      during infancy were 4.5 times greater than their peers who had never been exposed
      to anesthesia. However, study precision was inadequate to detect a clinically
      relevant difference in PSLE scores.

PMID- 24132013
TI  - Neonatal exposure to sevoflurane causes significant suppression of hippocampal
      long-term potentiation in postgrowth rats.
AB  - BACKGROUND: The inhaled anesthetic sevoflurane is commonly used for neonates in
      the clinical setting. Recent studies have indicated that exposure of neonatal
      rodents to sevoflurane causes acute widespread neurodegeneration and long-lasting
      neurocognitive dysfunction. Although acute toxic effects of sevoflurane on
      cellular viability in the hippocampus have been reported in some studies, little
      is known about the effects of neonatal sevoflurane exposure on long-term
      hippocampal synaptic plasticity, which has been implicated in the processes of
      learning and memory formation. Our study is the first to examine the long-term
      electrophysiological impact of neonatal exposure to a clinically relevant
      concentration of sevoflurane. METHODS: On postnatal day 7, rats were exposed to
      sevoflurane (1% or 2% for 2 hours) with oxygen. To eliminate the influence of
      blood gas abnormalities caused by sevoflurane-induced respiratory suppression, a
      group of rats were exposed to a high concentration of carbon dioxide (8% for 2
      hours) to duplicate respiratory disturbances caused by 2% sevoflurane exposure.
      RESULTS: Exposure of neonatal rats to 2% sevoflurane for 2 hours caused
      significant suppression of long-term potentiation (LTP) induction in the
      postgrowth period. There was no significant difference between the control group
      and the CO2-exposed group in LTP induction, indicating that sevoflurane-induced
      LTP suppression was not caused by blood gas abnormalities. CONCLUSION: Our
      present findings indicate that neonatal exposure to sevoflurane at a higher
      concentration can cause alterations in the hippocampal synaptic plasticity that
      persists into adulthood.

PMID- 24132014
TI  - General anesthesia in infancy is associated with learning disabilities-or not.

PMID- 24132015
TI  - Growth and oxidation of graphene on Rh(111).
AB  - The growth and oxidation of graphene supported on Rh(111) was studied in situ by
      high-resolution X-ray photoelectron spectroscopy. By variation of propene
      pressure and surface temperature the optimum growth conditions were identified,
      yielding graphene with low defect density. Oxidation of graphene was studied at
      temperatures between 600 and 1000 K, at an oxygen pressure of ~2 * 10(-6) mbar.
      The oxidation follows sigmoidal reaction kinetics. In the beginning, the reaction
      rate is limited by the number of defects, which represent the active sites for
      oxygen dissociation. After an induction period, the reaction rate increases and
      graphene is rapidly removed from the surface by oxidation. For graphene with a
      high defect density we found that the oxidation is faster. In general, a
      reduction of the induction period and a faster oxidation occur at higher
      temperatures.

PMID- 24132016
TI  - Structural characterization of water and ice in mesoporous SBA-15 silicas IV:
      partially filled cases for 86 A pore diameter.
AB  - Previous papers in this series have involved the study of water/ice in a sample
      of a mesoporous SBA-15 silica with a pore size of 86 A, filling-factors f of 1.15
      and 0.95. The present paper extends the study to partially filled samples with f
      = 0.6 and 0.4. It is found that the ice formed in the pores has characteristics
      that differ markedly from those seen in the previous measurements. For f = 0.6,
      there is a significant amount of hexagonal ice, as seen by the presence of the
      normal ice triplet. For f = 0.4, the triplet peaks are not seen, indicating the
      predominant formation of cubic ice superimposed on a broad diffuse scattering
      peak that is attributed to a defective form of low-density amorphous ice. A
      parameter-fitting routine has been used (as previously) to extract the variation
      of the peak intensities and shapes with temperature. A separate component
      analysis procedure confirms these conclusions and emphasizes the role of plastic
      ice in the phase conversion process for the 260-200 K temperature region. A
      comparison of the liquid phase data for filling-factors of 0.4 and 0.95 indicates
      that the structural characteristics of the water vary according to the thickness
      of the layer, as suggested by computer predictions. 

PMID- 24132017
TI  - Extracting signals robust to electrode number and shift for online simultaneous
      and proportional myoelectric control by factorization algorithms.
AB  - Previous research proposed the extraction of myoelectric control signals by
      linear factorization of multi-channel electromyogram (EMG) recordings from
      forearm muscles. This paper further analyses the theoretical basis for
      dimensionality reduction in high-density EMG signals from forearm muscles.
      Moreover, it shows that the factorization of muscular activation patterns in
      weights and activation signals by non-negative matrix factorization (NMF) is
      robust with respect to the channel configuration from where the EMG signals are
      obtained. High-density surface EMG signals were recorded from the forearm muscles
      of six individuals. Weights and activation signals extracted offline from 10
      channel configurations with varying channel numbers (6, 8, 16, 192 channels) were
      highly similar. Additionally, the method proved to be robust against electrode
      shifts in both transversal and longitudinal direction with respect to the muscle
      fibers. In a second experiment, six subjects directly used the activation signals
      extracted from high-density EMG for online goal-directed control tasks involving
      simultaneous and proportional control of two degrees-of-freedom of the wrist. The
      synergy weights for this control task were extracted from a reference
      configuration and activation signals were calculated online from the reference
      configuration as well as from the two shifted configurations, simulating
      electrode shift. Despite the electrode shift, the task completion rate, task
      completion time, and execution efficiency were generally not statistically
      different among electrode configurations. Online performances were also mostly
      similar when using either 6, 8, or 16 EMG channels. The robustness of the method
      to the number and location of channels, proved both offline and online, indicates
      that EMG signals recorded from forearm muscles can be approximated as linear
      instantaneous mixtures of activation signals and justifies the use of linear
      factorization algorithms for extracting, in a minimally supervised way, control
      signals for simultaneous multi-degree of freedom prosthesis control. 

PMID- 24132022
TI  - Impact of the genome-wide schizophrenia risk single nucleotide polymorphism
      (rs1625579) in miR-137 on brain structures in healthy individuals.

PMID- 24132023
TI  - Basic training requirements for the use of dental CBCT by dentists: a position
      paper prepared by the European Academy of DentoMaxilloFacial Radiology.
AB  - Cone beam CT (CBCT) is a relatively new imaging modality, which is now widely
      available to dentists for examining hard tissues in the dental and maxillofacial
      regions. CBCT gives a three-dimensional depiction of anatomy and pathology, which
      is similar to medical CT and uses doses generally higher than those used in
      conventional dental imaging. The European Academy of DentoMaxilloFacial Radiology
      recognizes that dentists receive training in two-dimensional dental imaging as
      undergraduates, but most of them have received little or no training in the
      application and interpretation of cross-sectional three-dimensional imaging. This
      document identifies the roles of dentists involved in the use of CBCT, examines
      the training requirements for the justification, acquisition and interpretation
      of CBCT imaging and makes recommendations for further training of dentists in
      Europe who intend to be involved in any aspect of CBCT imaging. Two levels of
      training are recognized. Level 1 is intended to train dentists who prescribe CBCT
      imaging, such that they may request appropriately and understand the resultant
      reported images. Level 2 is intended to train to a more advanced level and covers
      the understanding and skills needed to justify, carry out and interpret a CBCT
      examination. These recommendations are not intended to create specialists in CBCT
      imaging but to offer guidance on the training of all dentists to enable the safe
      use of CBCT in the dentoalveolar region. 

PMID- 24132024
TI  - The effect of scan parameters on cone beam CT trabecular bone microstructural
      measurements of the human mandible.
AB  - The objective of this study was to investigate the effect of different cone beam
      CT scan parameters on trabecular bone microstructure measurements. A human
      mandibular cadaver was scanned using a cone beam CT (3D Accuitomo 170; J.Morita,
      Kyota, Japan). 20 cone beam CT images were obtained using 5 different fields of
      view (4*4 cm, 6*6 cm, 8*8 cm, 10*10 cm and 10*5 cm), 2 types of rotation steps
      (180 degrees  and 360 degrees ) and 2 scanning resolutions (standard and high).
      Image analysis software was used to assess the trabecular bone microstructural
      parameters (number, thickness and spacing). All parameters were measured twice by
      one trained observer. Intraclass correlation coefficients showed high
      intraobserver repeatability (intraclass correlation coefficient, 0.95-0.97) in
      all parameters across all tested scan parameters. Trabecular bone microstructural
      measurements varied significantly, especially in smaller fields of view (p =
      0.001). There was no significant difference in the trabecular parameters when
      using different resolutions (number, p = 0.988; thickness, p = 0.960; spacing, p
      = 0.831) and rotation steps (number, p = 1.000; thickness, p = 0.954; spacing, p
      = 0.759). The scan field of view significantly influences the trabecular bone
      microstructure measurements. Rotation steps (180 degrees  or 360 degrees ) and
      resolution (standard or high) selections are not relevant. 

PMID- 24132025
TI  - An automated screening system for tuberculosis.
AB  - Automated screening systems are commonly used to detect some agent in a sample
      and take a global decision about the subject (e.g., ill/healthy) based on these
      detections. We propose a Bayesian methodology for taking decisions in
      (sequential) screening systems that considers the false alarm rate of the
      detector. Our approach assesses the quality of its decisions and provides lower
      bounds on the achievable performance of the screening system from the training
      data. In addition, we develop a complete screening system for sputum smears in
      tuberculosis diagnosis, and show, using a real-world database, the advantages of
      the proposed framework when compared to the commonly used count detections and
      threshold approach.

PMID- 24132026
TI  - Quality of the wireless electrocardiogram signal during physical exercise in
      different age groups.
AB  - Electrocardiographic (ECG) recordings are usually obtained at rest. In many
      cases, real-time ECG monitoring in the home environment during daily life would
      be useful, but that requires a wireless device. The purpose of this paper is to
      evaluate the quality of the wireless ECG signals during physical activities. The
      test data were collected both in a normal exercise environment and in a radio
      frequency (RF)-shielded and noiseless environment. 30 test persons performed
      running, biking, or Nordic walking exercises in normal indoor conditions, while
      electrical activity of the heart and acceleration of the body were measured by a
      VitalSens VS100 device (InteleSens). The acceleration data were also acquired
      with a DogIMU movement sensor (Domuset). Six more persons were measured in an RF
      shielded environment, while they followed a specific list of exercises to verify
      the tests of the first group. The list consisted of exercise movements, thought
      to introduce disturbance in the ECG signals. The collected data were classified
      into three quality classes, good (3%), moderate (66%), and poor (31%), based on
      the recognition of the QRS-complex and R-R intervals as well as the amount of
      disturbance. The accelerometer data were compared to the amount of noise in the
      ECG data. A clear correlation was found between increased noise and level of
      activity. Increasing age also appeared to decrease the ECG signal quality.
      Careful consideration of the quality of the data versus positive and negative
      features of wirelessness shows great potential for the wireless ECG in future
      home healthcare and fitness industries. 

PMID- 24132027
TI  - Cross-layer design for prompt and reliable transmissions over body area networks.
AB  - In this paper, we propose a cross-layer design to make ambulatory health
      monitoring via body area networks (BAN) more reliable and robust. The proposed
      design builds on our centralized body area network access scheme (CBAS), a
      receiver-initiated medium access control (MAC) scheme that improves the
      visibility of a BAN in a coexistent environment, where diverse networks with
      various physical and MAC protocols share the radio spectrum. The design enhances
      CBAS by incorporating a network layer scheme that improves the packet delivery
      ratio (PDR), while minimizing the need for multihop cooperative transmissions;
      thus, packet delay is less compromised to achieve higher PDRs. The MAC layer
      provides the network layer with local information about the quality of on-body
      links to enable the BAN to identify the most reliable links in a distributed
      manner. Extensive experimental results are presented, which give insights on how
      the proposed cross-layer design improves PDR and packet delay. Results show the
      effectiveness of the proposed design which takes advantage of dynamic scheduling
      and multihop relays as warranted by the link conditions.

PMID- 24132028
TI  - A bicluster-based Bayesian principal component analysis method for microarray
      missing value estimation.
AB  - Data generated from microarray experiments often suffer from missing values. As
      most downstream analyses need full matrices as input, these missing values have
      to be estimated. Bayesian principal component analysis (BPCA) is a well-known
      microarray missing value estimation method, but its performance is not
      satisfactory on datasets with strong local similarity structure. A bicluster
      based BPCA (bi-BPCA) method is proposed in this paper to fully exploit local
      structure of the matrix. In a bicluster, the most correlated genes and
      experimental conditions with the missing entry are identified, and BPCA is
      conducted on these biclusters to estimate the missing values. An automatic
      parameter learning scheme is also developed to obtain optimal parameters.
      Experimental results on four real microarray matrices indicate that bi-BPCA
      obtains the lowest normalized root-mean-square error on 82.14% of all missing
      rates. 

PMID- 24132029
TI  - A computational tool for preoperative breast augmentation planning in aesthetic
      plastic surgery.
AB  - Breast augmentation was the most commonly performed cosmetic surgery procedure in
      2011 in the United States. Although aesthetically pleasing surgical results can
      only be achieved if the correct breast implant is selected from a large variety
      of different prosthesis sizes and shapes available on the market, surgeons still
      rely on visual assessment and other subjective approaches for operative planning
      because of lacking objective evaluation tools. In this paper, we present the
      development of a software prototype for augmentation mammaplasty simulation
      solely based on 3-D surface scans, from which patient-specific finite-element
      models are generated in a semiautomatic process. The finite-element model is used
      to preoperatively simulate the expected breast shapes using physical soft-tissue
      mechanics. Our approach uses a novel mechanism based on so-called displacement
      templates, which, for a specific implant shape and position, describe the
      respective internal body forces. Due to a highly efficient numerical solver we
      can provide immediate visual feedback of the simulation results, and thus, the
      software prototype can be integrated smoothly into the medical workflow. The
      clinical value of the developed 3-D computational tool for aesthetic breast
      augmentation surgery planning is demonstrated in patient-specific use cases. 

PMID- 24132030
TI  - Multiple kernel learning in the primal for multimodal Alzheimer's disease
      classification.
AB  - To achieve effective and efficient detection of Alzheimer's disease (AD), many
      machine learning methods have been introduced into this realm. However, the
      general case of limited training samples, as well as different feature
      representations typically makes this problem challenging. In this paper, we
      propose a novel multiple kernel-learning framework to combine multimodal features
      for AD classification, which is scalable and easy to implement. Contrary to the
      usual way of solving the problem in the dual, we look at the optimization from a
      new perspective. By conducting Fourier transform on the Gaussian kernel, we
      explicitly compute the mapping function, which leads to a more straightforward
      solution of the problem in the primal. Furthermore, we impose the mixed L21 norm
      constraint on the kernel weights, known as the group lasso regularization, to
      enforce group sparsity among different feature modalities. This actually acts as
      a role of feature modality selection, while at the same time exploiting
      complementary information among different kernels. Therefore, it is able to
      extract the most discriminative features for classification. Experiments on the
      ADNI dataset demonstrate the effectiveness of the proposed method. 

PMID- 24132031
TI  - On the seamless, harmonized use of ISO/IEEE11073 and openEHR.
AB  - Standardized exchange of clinical information is a key factor in the provision of
      high quality health care systems. In this context, the openEHR specification
      facilitates the management of health data in electronic health records (EHRs),
      while the ISO/IEEE11073 (also referred to as X73PHD) family of standards provides
      a reference framework for medical device interoperability. Hospitals and health
      care providers using openEHR require flawless integration of data coming from
      external sources, such as X73PHD. Hence, a harmonization process is crucial for
      achieving a seamless, coherent use of those specifications in real scenarios.
      Such harmonization is the aim of this paper. Thus, the classes and attributes of
      a representative number of X73PHD specializations for medical devices--weight,
      temperature, blood pressure, pulse and heart rate, oximetry, and
      electrocardiograph--along with the X73PHD core document--ISO/IEEE11073-20601-
      have been analyzed and mapped to openEHR archetypes. The proposed methodology
      reuses the existing archetypes when possible and suggests new ones--or
      appropriate modifications--otherwise. As a result, this paper analyzes the
      inconsistencies found and the implications thereof in the coordinated use of
      these two standards. The procedure has also shown how existing standards are able
      to influence the archetype development process, enhancing the existing archetype
      corpus.

PMID- 24132032
TI  - Using a dynamic tracking filter to extract distortion-product otoacoustic
      emissions evoked with swept-tone signals.
AB  - Distortion-product otoacoustic emissions (DPOAEs) are sound energy generated by
      healthy inner ears when stimulated by two tones. Since DPOAEs are physiologically
      related with the functional status of the inner ear, they have been widely used
      as a clinical tool in hearing screening and diagnoses. Currently, almost all
      DPOAEs recording systems use pure tones as the stimuli and can test only one
      frequency at a time, resulting in low efficiency and insufficient resolution. In
      this study, conventional pure tones were replaced by swept tones with time
      varying frequencies to overcome the limitation of current DPOAEs measurements. A
      tracking filter with dynamic center frequencies was proposed to extract the swept
      tone DPOAEs from recorded signals with stimulus artifacts and background noises.
      The results of this study showed that the dynamic tracking filter had great
      performance in effectively extracting the swept-tone DPOAEs under different noise
      conditions for both the simulation and experimental data. The spectrogram of the
      extracted swept-tone DPOAEs could provide useful information to examine the
      functional status of the inner ear and to identify the detailed frequency regions
      of the hearing loss. These preliminary findings suggested that the swept-tone
      DPOAEs might be useful for developing a more efficient and accurate tool for
      hearing loss screening in the clinic.

PMID- 24132033
TI  - Fuzzy neural network-based adaptive control for a class of uncertain nonlinear
      stochastic systems.
AB  - This paper studies an adaptive tracking control for a class of nonlinear
      stochastic systems with unknown functions. The considered systems are in the
      nonaffine pure-feedback form, and it is the first to control this class of
      systems with stochastic disturbances. The fuzzy-neural networks are used to
      approximate unknown functions. Based on the backstepping design technique, the
      controllers and the adaptation laws are obtained. Compared to most of the
      existing stochastic systems, the proposed control algorithm has fewer adjustable
      parameters and thus, it can reduce online computation load. By using Lyapunov
      analysis, it is proven that all the signals of the closed-loop system are
      semiglobally uniformly ultimately bounded in probability and the system output
      tracks the reference signal to a bounded compact set. The simulation example is
      given to illustrate the effectiveness of the proposed control algorithm. 

PMID- 24132034
TI  - Evolutionary algorithms with segment-based search for multiobjective optimization
      problems.
AB  - This paper proposes a variation operator, called segment-based search (SBS), to
      improve the performance of evolutionary algorithms on continuous multiobjective
      optimization problems. SBS divides the search space into many small segments
      according to the evolutionary information feedback from the set of current
      optimal solutions. Two operations, micro-jumping and macro-jumping, are
      implemented upon these segments in order to guide an efficient information
      exchange among "good" individuals. Moreover, the running of SBS is adaptive
      according to the current evolutionary status. SBS is activated only when the
      population evolves slowly, depending on general genetic operators (e.g., mutation
      and crossover). A comprehensive set of 36 test problems is employed for
      experimental verification. The influence of two algorithm settings (i.e., the
      dimensionality and boundary relaxation strategy) and two probability parameters
      in SBS (i.e., the SBS rate and micro-jumping proportion) are investigated in
      detail. Moreover, an empirical comparative study with three representative
      variation operators is carried out. Experimental results show that the
      incorporation of SBS into the optimization process can improve the performance of
      evolutionary algorithms for multiobjective optimization problems. 

PMID- 24132035
TI  - Strain sensors based on chromium nanoparticle arrays.
AB  - High sensitivity strain sensors have been fabricated by depositing chromium (Cr)
      nanoparticles between silver interdigital electrodes coated on the substrate of a
      flexible plastic material like polyethylene terephthalate. A gas phase cluster
      beam deposition system was used for the preparation of the nanoparticle arrays
      with a well-defined conductance. We demonstrate that the conductance of the
      nanoparticle arrays is dominated by the quantum transport between the closely
      spaced nanoparticles. Compared to the traditional metallic foil or semiconductor
      strain sensors, this kind of strain sensor demonstrates both a higher gauge
      factor, which can be as large as the order of 100, and a wider dynamic range,
      with a workable maximum applied strain beyond 3%. 

PMID- 24132036
TI  - CO2 fixation employing an iridium(I)-hydroxide complex.
AB  - The reactivity of a number of Ir(I) complexes towards CO2 is explored using
      [Ir(NHC)(OH)] as a key synthon. CO2 insertion into Ir-O and Ir-N bonds proved
      facile, yielding a number of Ir(I)-carbonates and -carbamates. Most importantly,
      reaction between CO2 and Ir(I)-OH led to isolation of the novel [{Ir(I)}2-(MU
      kappa(1):kappa(2)-CO3)] complex. 

PMID- 24132037
TI  - Critical care medicine in the United States: addressing the intensivist shortage
      and image of the specialty.
AB  - Intensivists are increasingly needed to care for the critically ill and manage
      ICUs as ICU beds, utilization, acuity of illness, complexity of care and costs
      continue to rise. However, there is a nationwide shortage of intensivists that
      has occurred despite years of well publicized warnings of an impending workforce
      crisis from specialty societies and the federal government. The magnitude of the
      intensivist shortfall, however, is difficult to determine because there are many
      perspectives of optimal ICU administration, patient coverage and intensivist
      availability and a lack of national data on intensivist practices. Nevertheless,
      the intensivist shortfall is quite real as evidenced by the alternative solutions
      that hospitals are deploying to provide care for their critically ill patients.
      In the midst of these manpower struggles, the critical care environment is
      dynamically changing and becoming more stressful. Severe hospital bed
      availability and fiscal constraints are forcing ICUs to alter their approaches to
      triage, throughput and unit staffing. National and local organizations are
      mandating that hospitals comply with resource intensive and arguably unproven
      initiatives to monitor and improve patient safety and quality, and informatics
      systems. Lastly, there is an ongoing sense of professional dissatisfaction among
      intensivists and a lack of public awareness that critical care medicine is even a
      distinct specialty. This article offers proposals to increase the adult
      intensivist workforce through expansion and enhancements of internal medicine
      based critical care training programs, incentives for recent graduates to enter
      the critical care medicine field, suggestions for improvements in the critical
      care profession and workplace to encourage senior intensivists to remain in the
      field, proactive marketing of critical care, and expanded engagement by the
      critical care societies in the challenges facing intensivists. 

PMID- 24132038
TI  - Inhaled nitric oxide does not reduce mortality in patients with acute respiratory
      distress syndrome regardless of severity: systematic review and meta-analysis.
AB  - OBJECTIVE: Treatment with inhaled nitric oxide improves oxygenation but not
      survival in mechanically ventilated patients with acute respiratory distress
      syndrome, but the effect may depend on the severity of hypoxemia. Our objective
      was to determine whether nitric oxide reduces hospital mortality in patients with
      severe acute respiratory distress syndrome (PaO2/FIO2 <= 100 mm Hg) but not in
      patients with mild-moderate acute respiratory distress syndrome (100 < PaO2/FIO2
      <= 300 mm Hg) at the time of randomization. DATA SOURCES: Data were collected
      from Medline, Embase, and Cochrane CENTRAL electronic databases (inception to May
      2013); proceedings from five conferences (to May 2013); and trial registries
      (http://www.clinicaltrials.gov and http://www.controlled-trials.com). No language
      restrictions were applied. STUDY SELECTION: Two authors independently selected
      parallel-group randomized controlled trials comparing nitric oxide with control
      (placebo or no gas) in mechanically ventilated adults or postneonatal children
      with acute respiratory distress syndrome. DATA EXTRACTION: Two authors
      independently extracted data from included trials. Trial investigators provided
      subgroup data. Meta-analyses used within-trial subgroups and random-effects
      models. DATA SYNTHESIS: Nine trials (n = 1,142 patients) met inclusion criteria.
      Overall methodological quality was good. Nitric oxide did not reduce mortality in
      patients with severe acute respiratory distress syndrome (risk ratio, 1.01 [95%
      CI, 0.78-1.32]; p = 0.93; n = 329, six trials) or mild-moderate acute respiratory
      distress syndrome (risk ratio, 1.12 [95% CI, 0.89-1.42]; p = 0.33; n = 740, seven
      trials). Risk ratios were similar between subgroups (interaction p = 0.53). There
      was no between-trial heterogeneity in any analysis (I = 0%). Varying the
      PaO2/FIO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not
      identify any threshold at which the nitric oxide-treated patients had lower
      mortality relative to controls. CONCLUSIONS: Nitric oxide does not reduce
      mortality in adults or children with acute respiratory distress syndrome,
      regardless of the degree of hypoxemia. Given the lack of related ongoing or
      recently completed randomized trials, new data addressing the effectiveness of
      nitric oxide in patients with acute respiratory distress syndrome and severe
      hypoxemia will not be available for the foreseeable future.

PMID- 24132039
TI  - Molecular tectonics: anion control of dimensionality and connectivity in meta
      pyridyl appended tetramercaptotetrathiacalix[4]arene based silver coordination
      networks.
AB  - The combination of the same organic tecton 1, a meta-pyridyl appended
      tetramercaptotetrathiacalix[4]arene in 1,3-alternate conformation offering four
      pyridyl units and eight thioether groups, with three silver salts AgX (X = BF4(
      ), NO3(-) and SbF6(-)) leads, under identical conditions (concentration,
      temperature and solvent system), to the formation of different silver
      coordination networks. Both the connectivity and the dimensionality of the three
      silver coordination networks depend on the nature of the anion used as a counter
      ion. Whereas the weakly coordinating BF4(-) anion does not participate in the
      formation of the non-tubular 1D coordination network, the coordinating NO3(-)
      anion is bound to the metal cation and this leads to the formation of a tubular
      1D silver coordination network. In both cases, the eight S atoms of the tecton 1
      do not take part in the binding of the cation. In marked contrast, when the SbF6(
      ) anion is used as a counter ion, the organic tecton 1 behaves as a
      tetrakismonodentate through its four meta-pyridyl moieties and as a bischelating
      unit of the SCCS type leading thus to the formation of a porous 3D diamondoid
      type network.

PMID- 24132040
TI  - Hierarchically structured Co3O4@Pt@MnO2 nanowire arrays for high-performance
      supercapacitors.
AB  - Here we proposed a novel architectural design of a ternary MnO2-based electrode -
      a hierarchical Co3O4@Pt@MnO2 core-shell-shell structure, where the complemental
      features of the three key components (a well-defined Co3O4 nanowire array on the
      conductive Ti substrate, an ultrathin layer of small Pt nanoparticles, and a thin
      layer of MnO2 nanoflakes) are strategically combined into a single entity to
      synergize and construct a high-performance electrode for supercapacitors. Owing
      to the high conductivity of the well-defined Co3O4 nanowire arrays, in which the
      conductivity was further enhanced by a thin metal (Pt) coating layer, in
      combination with the large surface area provided by the small MnO2 nanoflakes,
      the as-fabricated Co3O4@Pt@MnO2 nanowire arrays have exhibited high specific
      capacitances, good rate capability, and excellent cycling stability. The
      architectural design demonstrated in this study provides a new approach to
      fabricate high-performance MnO2-based nanowire arrays for constructing next
      generation supercapacitors.

PMID- 24132041
TI  - Electron transport through a quantum dot assisted by cavity photons.
AB  - We investigate transient transport of electrons through a single quantum dot
      controlled by a plunger gate. The dot is embedded in a finite wire with length Lx
      assumed to lie along the x-direction with a parabolic confinement in the y
      direction. The quantum wire, originally with hard-wall confinement at its ends,
      +/-Lx/2, is weakly coupled at t = 0 to left and right leads acting as external
      electron reservoirs. The central system, the dot and the finite wire, is strongly
      coupled to a single cavity photon mode. A non-Markovian density-matrix formalism
      is employed to take into account the full electron-photon interaction in the
      transient regime. In the absence of a photon cavity, a resonant current peak can
      be found by tuning the plunger-gate voltage to lift a many-body state of the
      system into the source-drain bias window. In the presence of an x-polarized
      photon field, additional side peaks can be found due to photon-assisted
      transport. By appropriately tuning the plunger-gate voltage, the electrons in the
      left lead are allowed to undergo coherent inelastic scattering to a two-photon
      state above the bias window if initially one photon was present in the cavity.
      However, this photon-assisted feature is suppressed in the case of a y-polarized
      photon field due to the anisotropy of our system caused by its geometry. 

PMID- 24132042
TI  - Declining and stabilising trends in prevalence of overweight and obesity in
      Dutch, Turkish, Moroccan and South Asian children 3-16 years of age between 1999
      and 2011 in the Netherlands.
AB  - OBJECTIVE: In many developed countries, overweight and obesity prevalence seems
      to stabilise. The aim of this study was to determine trends between 1999 and 2011
      in overweight and obesity prevalence, and mean Body Mass Index (BMI) z-score in
      Dutch, Turkish, Moroccan and Surinamese South Asian children in the Netherlands.
      DESIGN: A cross-sectional population-based study with 136 080 measurements of
      height and weight of 73 290 children aged 3-16 years. BMI class and BMI z-score
      were determined with the latest International Obesity Taskforce (IOTF) criteria,
      with overweight defined as an adult BMI equivalent >= 25 and obesity >= 30. Time
      trends per year were analysed using logistic and linear regression analyses.
      RESULTS: The prevalence of overweight in Dutch children declined from 13% to 11%
      (OR 0.960; 95% CI 0.954 to 0.965), but increased in Turkish children from 25% to
      32% (OR 1.028; 95% CI 1.020 to 1.036). In Moroccan and Surinamese South Asian
      children, overweight rates were stable, but obesity prevalence decreased (OR
      0.973; 95% CI 0.957 to 0.989, OR 0.964; 95% CI 0.943 to 0.985, respectively) as
      well as the mean BMI z-score (B=-0.010; 95% CI -0.014 to -0.006, B=-0.010; 95% CI
      -0.016 to -0.004). In Turkish children, trends limited to the period 2007-2011
      showed no statistically significant relationship for all outcome measures.
      CONCLUSIONS: The decrease in obesity prevalence in Dutch, Moroccan and Surinamese
      South Asian children suggests that overweight children became less adipose. The
      stabilising trend in overweight and obesity prevalence in Turkish children since
      2007 may signify a levelling off for this ethnic group.

PMID- 24132043
TI  - Paroxysmal autonomic dysfunction in a patient with chronic rhinosinusitis.

PMID- 24132044
TI  - Adherence to a web-based physical activity intervention for patients with knee
      and/or hip osteoarthritis: a mixed method study.
AB  - BACKGROUND: Web-based interventions show promise in promoting a healthy
      lifestyle, but their effectiveness is hampered by high rates of nonusage.
      Predictors and reasons for (non)usage are not well known. Identifying which
      factors are related to usage contributes to the recognition of subgroups who
      benefit most from Web-based interventions and to the development of new
      strategies to increase usage. OBJECTIVE: The aim of this mixed methods study was
      to explore patient, intervention, and study characteristics that facilitate or
      impede usage of a Web-based physical activity intervention for patients with knee
      and/or hip osteoarthritis. METHODS: This study is part of a randomized controlled
      trial that investigated the effects of Web-based physical activity intervention.
      A total of 199 participants between 50-75 years of age with knee and/or hip
      osteoarthritis were randomly assigned to a Web-based intervention (n=100) or a
      waiting list (n=99). This mixed methods study used only data from the individuals
      allocated to the intervention group. Patients were defined as users if they
      completed at least 6 out of 9 modules. Logistic regression analyses with a
      stepwise backward selection procedure were executed to build a multivariate
      prediction usage model. For the qualitative part, semistructured interviews were
      conducted. Both inductive and deductive analyses were used to identify patterns
      in reported reasons for nonusage. RESULTS: Of the 100 participants who received a
      password and username, 46 completed 6 modules or more. Multivariate regression
      analyses revealed that higher age (OR 0.94, P=.08) and the presence of a
      comorbidity (OR 0.33, P=.02) predicted nonusage. The sensitivity analysis
      indicated that the model was robust to changes in the usage parameter. Results
      from the interviews showed that a lack of personal guidance, insufficient
      motivation, presence of physical problems, and low mood were reasons for
      nonusage. In addition, the absence of human involvement was viewed as a
      disadvantage and it negatively impacted program usage. Factors that influenced
      usage positively were trust in the program, its reliability, functionality of the
      intervention, social support from family or friends, and commitment to the
      research team. CONCLUSIONS: In this mixed methods study, we found patient,
      intervention, and study factors that were important in the usage and nonusage of
      a Web-based PA intervention for patients with knee and/or hip osteoarthritis.
      Although the self-guided components offer several advantages, particularly in
      relation to costs, reach, and access, we found that older patients and
      participants with a comorbid condition need a more personal approach. For these
      groups the integration of Web-based interventions in a health care environment
      seems to be promising.

PMID- 24132045
TI  - Developing Fe3O4 nanoparticles into an efficient multimodality imaging and
      therapeutic probe.
AB  - A rapid ligand-exchange method was developed to transfer high quality hydrophobic
      magnetite nanocrystals into water-soluble NPs by using protocatechuic acid as a
      ligand via homogenous reaction. After ligand exchange, the magnetite nanocrystals
      not only exhibited outstanding stability in water, but also maintained high
      crystallinity and saturation magnetization. Cell viability experiments
      demonstrated good biocompatibility of the NPs. For 12 nm magnetite nanoparticles
      (NPs), the small hydrodynamic size of 14 nm enabled a high T1 relaxivity of 17.8
      mM(-1) s(-1) while high saturation magnetization of 77.8 emu g(-1) enabled the
      NPs to exhibit a high T2 relaxivity of 220 mM(-1) s(-1) in MRI phantom
      experiments. In vivo MR imaging experiments further confirmed that the NPs were
      eminent T1 and T2 contrast agents. Moreover, the high quality NPs can be used as
      excellent magnetic heating agents under an alternating magnetic field. With all
      those features, including multimodality imaging and magnetic hyperthermia, the
      NPs can be used as single compound multifunctional agents for various biomedical
      applications, especially for cancer diagnosis and therapy. 

PMID- 24132046
TI  - Emergence of nanoscale inhomogeneity in the superconducting state of a
      homogeneously disordered conventional superconductor.
AB  - The notion of spontaneous formation of an inhomogeneous superconducting state is
      at the heart of most theories attempting to understand the superconducting state
      in the presence of strong disorder. Using scanning tunneling spectroscopy and
      high resolution scanning transmission electron microscopy, we experimentally
      demonstrate that under the competing effects of strong homogeneous disorder and
      superconducting correlations, the superconducting state of a conventional
      superconductor, NbN, spontaneously segregates into domains. Tracking these
      domains as a function of temperature we observe that the superconducting domains
      persist across the bulk superconducting transition, Tc, and disappear close to
      the pseudogap temperature, T*, where signatures of superconducting correlations
      disappear from the tunneling spectrum and the superfluid response of the system. 

PMID- 24132047
TI  - Synthesis and characterisation of tetramethylfulvene complexes of ruthenium.
AB  - Reactions of [RuCp*Cl2]2 with dibenzoylmethane and triethylamine, in either
      dichloromethane or toluene, produced the complexes [RuCl(eta(6)
      C5Me4CH2)(PhCOCCOPh)] (1) and [RuCl3(eta(6)-C5Me4CH2)][RuCp*(C6H5CH3)] (2)
      respectively under mild conditions. Both compounds 1 and 2 are examples of an
      unusual tetramethylfulvene-ruthenium structure, obtained by deprotonation of the
      pentamethylcyclopentadienyl ligand, and were characterised by single-crystal X
      ray diffraction. 

PMID- 24132048
TI  - Resonant ultrasonic spectroscopy and resonant piezoelectric spectroscopy in
      ferroelastic lead phosphate, Pb3(PO4)2.
AB  - Elastic properties of the ferroelastic compound Pb3(PO4)2 were investigated using
      resonant ultrasonic spectroscopy. Results show softening of the mechanical
      resonance frequencies at the D3m -> C2/c ferroelastic transition temperature
      Ttrans = 453.6 K with no noticeable frequency dispersion. The reduction of
      resonance frequencies corresponds to 25% softening of the effective elastic
      constants at Ttrans relative to the value at 700 K. The data analysis indicates
      that the elastic precursor softening is driven by a displacive soft mode that is
      coupled to the order-disorder movements of Pb atoms around the rhombohedral
      threefold axis, which gives rise to local monoclinicity in the paraelastic phase.
      Finally, resonant piezoelectric spectroscopy (RPS) is used to determine if
      microstructures are polar in the cubic phase. RPS measurements find no evidence
      of piezoelectric signals in Pb3(PO4)2, confirming that the possible polar
      behavior detected using second harmonic generation is due to crystal
      imperfections.

PMID- 24132049
TI  - A mixed dicarboxylate strut approach to enhancing catalytic activity of a de novo
      urea derivative of metal-organic framework UiO-67.
AB  - A hydrogen-bond donating MOF catalyst based on the framework, containing both
      urea-functionalized dicarboxylate and biphenyl-4,4'-dicarboxylate struts, was
      synthesized by a de novo route. The mixed strut framework has larger pore sizes
      and improved catalytic activity for Henry reactions than the pure strut analogue,
      which contains only the urea-functionalized dicarboxylate linker. 

PMID- 24132051
TI  - Combinatorial generation of droplets by controlled assembly and coalescence.
AB  - We describe a microfluidic system for generating a sequence of liquid droplets of
      multiple concentrations in a single experimental condition. The series of final
      droplets has the combination of the compositions varying periodically, with
      polydispersity of the size less than 8%. By utilizing the design of the
      microchannel geometry and the passive control of three immiscible fluids (oil,
      water, and air) including generation, breakup, separation and coalescence of
      droplets, we can change the system to generate diverse sets of combination of
      materials. The device can be used for testing different concentration of
      materials in picoliter volumes and developing a new way to deliver dynamic
      signals of chemicals with microfluidics. 

PMID- 24132050
TI  - Peripheral atherosclerosis in patients with arterial erectile dysfunction.
AB  - Erectile dysfunction (ED) develops owing to psychogenic, organic or/and both of
      these two factors. The aim of this study was to investigate the relationship
      between penile cavernosal arterial flow and peripheral atherosclerosis in men
      with ED. This study was conducted on 102 patients who had presented to Radiology
      Clinic with a prediagnosis of ED. Diabetes, hypertension (HT) and smoking were
      recorded. Blood were taken from all patients for analysis of fasting blood
      glucose, total cholesterol and high-density lipoprotein level. All the patients
      underwent high-resolution penile colour Doppler ultrasound (CDUS). The peak
      systolic velocity and the end-diastolic velocity values in the bilateral
      cavernosal arteries were recorded. At the same session, all the patients
      underwent evaluation for bilateral common carotid artery and femoral artery
      intima media thickness and for the presence of atherosclerotic plaque. Patients
      were classified as ED of arterial origin and non-arterial origin according to
      penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and
      the remaining 59 (57.8%) were contained in non-arterial ED. There was a
      significant difference between groups for diabetes mellitus (DM), HT,
      atherosclerotic cardiovascular diseases (ACVD) and total cholesterol level
      (P<0.05). There was also a significant difference between groups for the presence
      of plaque in the carotid and the femoral artery (P<0.05). The relationship
      between smoking and arterial ED was not found to be statistically significant
      (P>0.05). Non-diagnosed or silent DM, HT and ACVD can have roles in the etiology
      of arterial ED. Patients who are diagnosed as having arterial ED with Doppler
      Ultrasound should also be evaluated with B-mode ultrasonography for other
      peripheral vascular atherosclerotic processes. In this way, subclinical cases can
      be detected and further possible complications can be avoided.

PMID- 24132053
TI  - Symptoms of obstructive sleep apnoea are treated by adenotonsillectomy, but
      without change in neurocognitive outcome.

PMID- 24132052
TI  - Abnormal brain activity during a reward and loss task in opiate-dependent
      patients receiving methadone maintenance therapy.
AB  - A core feature of human drug dependency is persistence in seeking and using drugs
      at the expense of other life goals. It has been hypothesized that addiction is
      associated with overvaluation of drug-related rewards and undervaluation of
      natural, nondrug-related rewards. Humans additionally tend to persist in using
      drugs despite adverse consequences. This suggests that the processing of both
      rewarding and aversive information may be abnormal in addictions. We used fMRI to
      examine neural responses to reward and loss events in opiate-dependent patients
      receiving methadone maintenance treatment (MMT, n=30) and healthy controls (n=23)
      using nondrug-related stimuli. Half of the patients were scanned after/before
      daily methadone intake (ADM/BDM patient groups). During reward trials, patients
      as a whole exhibited decreased neural discrimination between rewarding and
      nonrewarding outcomes in the dorsal caudate. Patients also showed reduced neural
      discrimination in the ventral striatum with regard to aversive and nonaversive
      outcomes and failed to encode successful loss avoidance as a reward signal in the
      ventral striatum. Patients also showed decreased insula activation during the
      anticipation/decision phase of loss events. ADM patients exhibited increased loss
      signals in the midbrain/parahippocampal gyrus, possibly related to a
      disinhibition of dopamine neurons. This study suggests that patients with opiate
      dependency on MMT exhibit abnormal brain activations to nondrug-related rewarding
      and loss events. Our findings add support to proposals that treatments for opiate
      addiction should aim to increase the reward value of nondrug-related rewarding
      events and highlight the importance of potential abnormalities in aversive
      information processing. 

PMID- 24132054
TI  - Central venous pressure cannot predict fluid-responsiveness.

PMID- 24132055
TI  - Animal care practices in research on biological rhythms and sleep.

PMID- 24132057
TI  - A randomized controlled trial with bright light and melatonin for the treatment
      of delayed sleep phase disorder: effects on subjective and objective sleepiness
      and cognitive function.
AB  - Delayed sleep phase disorder (DSPD) is a circadian rhythm sleep disorder.
      Patients with DSPD have problems initiating sleep if they go to bed at a
      conventional time, and they often have problems waking at desired times. If they
      rise early in the morning, they usually experience severe sleepiness during
      morning hours. In the present study, we investigated the short- and long-term
      effects on measures of subjective and objective sleepiness and cognitive function
      of bright light and melatonin treatment alongside gradually advanced rise times
      in adolescents and young adults. Four treatment conditions were used in the short
      term intervention (2 weeks): dim light (placebo) + placebo capsule, bright light
      + placebo capsule, dim light (placebo) + melatonin capsule, and bright light +
      melatonin capsule. This was followed by a long-term intervention (3 months)
      including 2 conditions: no treatment and combined bright light + melatonin
      treatment. Effects of treatment on sleepiness and fatigue were the primary
      outcome measures, and effects on cognitive function were secondary outcome
      measures. On a gradual advancement of the rise time schedule, all treatment
      conditions (bright light, melatonin, combination, and placebo) were almost
      equally effective in improving subjective daytime sleepiness, fatigue, and
      cognitive function in the 2-week study. The 2-week intervention showed no effect
      on objective sleepiness. Long-term treatment increased some of the positive
      effects seen after 2 weeks. The combined bright light and melatonin treatment
      improved subjective daytime sleepiness, fatigue, and cognitive function in the 3
      month study. The no-treatment group returned to baseline values on most
      variables. In conclusion, a gradual advancement of rise times seems to produce
      positive effects on subjective sleepiness, fatigue, and cognitive performance
      during short-term treatment of patients with DSPD. However, the benefits from
      gradually advanced rise times seem to wear off, suggesting that the continuation
      of bright light and melatonin treatment is beneficial to maintain positive
      effects over time. 

PMID- 24132059
TI  - Daily physical activity patterns of children with delayed eating behaviors.
AB  - Night eating syndrome (NES) is a delayed pattern of energy intake. It is unknown
      if symptoms associated with this syndrome are accompanied by a delayed pattern of
      physical activity. This study examines the relationship between physical activity
      patterns and delayed eating behaviors in children. Children from the QUALITY
      cohort (n = 269, 45% female, aged 8-11 y) completed the Night Eating
      Questionnaire (NEQ), which measures NES symptoms on a continuous scale and
      identifies single NES symptoms. Daily accelerometer data were transformed into
      mean counts per wear-time minute for each hour of the day. Children with high NEQ
      scores had higher levels of daily (p < 0.001) and evening physical activity (p =
      0.05) and reached 75% of their total daily physical activity 20 minutes later
      than children with low NEQ scores (p < 0.05). Excessive evening snacking and a
      strong urge to eat in the evening or at night were the symptoms most related to
      these physical activity patterns. Children with delayed eating behaviors had
      higher levels of physical activity in the late morning and evening and a delayed
      physical activity pattern compared to children with no or fewer symptoms. Future
      research is needed to determine if physical activity plays a role in the onset or
      maintenance of night eating. 

PMID- 24132058
TI  - Circadian phase and its relationship to nighttime sleep in toddlers.
AB  - Circadian phase and its relation to sleep are increasingly recognized as
      fundamental factors influencing human physiology and behavior. Dim light
      melatonin onset (DLMO) is a reliable marker of the timing of the circadian clock,
      which has been used in experimental, clinical, and descriptive studies in the
      past few decades. Although DLMO and its relationship to sleep have been well
      documented in school-aged children, adolescents, and adults, very little is known
      about these processes in early childhood. The purpose of this study was 1) to
      describe circadian phase and phase angles of entrainment in toddlers and 2) to
      examine associations between DLMO and actigraphic measures of children's
      nighttime sleep. Participants were 45 healthy toddlers aged 30 to 36 months (33.5
      +/- 2.2 months; 21 females). After sleeping on a parent-selected schedule for 5
      days (assessed with actigraphy and diaries), children participated in an in-home
      DLMO assessment involving the collection of saliva samples every 30 minutes for 6
      hours. Average bedtime was 2015 +/- 0036 h, average sleep onset time was 2043 +/-
      0043 h, average midsleep time was 0143 +/- 0038 h, and average wake time was 0644
      +/- 0042 h. Average DLMO was 1929 +/- 0051 h, with a 3.5-hour range. DLMO was
      normally distributed; however, the distribution of the bedtime, sleep onset time,
      and midsleep phase angles of entrainment were skewed. On average, DLMO occurred
      47.8 +/- 47.6 minutes (median = 39.4 minutes) before bedtime, 74.6 +/- 48.0
      minutes (median = 65.4 minutes) before sleep onset time, 6.2 +/- 0.7 hours
      (median = 6.1 hours) before midsleep time, and 11.3 +/- 0.7 hours before wake
      time. Toddlers with later DLMOs had later bedtimes (r = 0.46), sleep onset times
      (r = 0.51), midsleep times (r = 0.66), and wake times (r = 0.65) (all p < 0.001).
      Interindividual differences in toddlers' circadian phase are large and associated
      with their sleep timing. The early DLMOs of toddlers indicate a maturational
      delay in the circadian timing system between early childhood and adolescence.
      These findings are a first step in describing the fundamental properties of the
      circadian system in toddlers and have important implications for understanding
      the emergence of sleep problems and the consequences of circadian misalignment in
      early childhood. 

PMID- 24132060
TI  - Modeling interindividual differences in spontaneous internal desynchrony
      patterns.
AB  - A physiologically based mathematical model of a putative sleep-wake regulatory
      network is used to investigate the transition from typical human sleep patterns
      to spontaneous internal desynchrony behavior observed under temporal isolation
      conditions. The model sleep-wake regulatory network describes the
      neurotransmitter-mediated interactions among brainstem and hypothalamic neuronal
      populations that participate in the transitions between wake, rapid eye movement
      (REM) sleep, and non-REM (NREM) sleep. Physiologically based interactions among
      these sleep-wake centers and the suprachiasmatic nucleus (SCN), whose activity is
      driven by an established circadian oscillator model, mediate circadian modulation
      of sleep-wake behavior. When the sleep-wake and circadian rhythms are
      synchronized, the model simulates stereotypically normal human sleep-wake
      behavior within the limits of individual variation, including typical NREM-REM
      cycling across the night. When effects of temporal isolation are simulated by
      increasing the period of the sleep-wake cycle, the model replicates spontaneous
      internal desynchrony with the appropriate dependence of multiple features of REM
      sleep on circadian phase. In temporal isolation experiments, subjects have
      exhibited different desynchronized sleep-wake behaviors. Our model can generate
      similar ranges of desynchronized behaviors by variations in the period of the
      sleep-wake cycle and the strength of interactions between the SCN and the sleep
      wake centers. Analysis of the model suggests that similar mechanisms underlie
      several different desynchronized behaviors and that the phenomenon of phase
      trapping may be dependent on SCN modulation of REM sleep-promoting centers. These
      results provide predictions for physiologically plausible mechanisms underlying
      interindividual variations in sleep-wake behavior observed during temporal
      isolation experiments. 

PMID- 24132061
TI  - Exposure to shift work as a risk factor for diabetes.
AB  - Using telephone survey data from 1111 retired older adults (>=65 years; 634 male,
      477 female), we tested the hypothesis that exposure to shift work might result in
      increased self-reported diabetes. Five shift work exposure bins were considered:
      0 years, 1-7 years, 8-14 years, 15-20 years, and >20 years. Shift work exposed
      groups showed an increased proportion of self-reported diabetes (chi(2) = 22.32,
      p < 0.001), with odds ratios (ORs) of about 2 when compared to the 0-year group.
      The effect remained significant after adjusting for gender and body mass index
      (BMI) (OR >= 1.4; chi(2) = 10.78, p < 0.05). There was a significant shift work
      exposure effect on BMI (chi(2) = 80.70, p < 0.001) but no significant gender
      effect (chi(2) = 0.37, p > 0.50). 

PMID- 24132064
TI  - Congenital malformation of the posterior fossa: new insights.

PMID- 24132065
TI  - Basic genetic principles applied to posterior fossa malformations.
AB  - Recent advances in neuroimaging techniques turned possible for neuroradiologists
      to be frequently the first one to detect possible brain structural anomalies.
      However, with all the recent advances in genetics and embryology, understanding
      posterior fossa malformation's principles is being hardest to be achieved than
      previously. Studies in vertebrate models provide a developmental framework in
      which to categorize human hindbrain malformations and serve to inform our
      thinking regarding candidate genes involved in disrupted developmental processes.
      The main focus of this review was to survey the basic principles of the
      rhombomere division, anteroposterior and dorsoventral patterning, alar and basal
      zone concept, and axonal path finding to integrate the knowledge of human
      hindbrain malformations for better understanding the genetic basis of hindbrain
      development. 

PMID- 24132066
TI  - Fetal magnetic resonance imaging of the posterior fossa malformations.

PMID- 24132067
TI  - Imaging findings in congenital cranial dysinnervation disorders.
AB  - In 2002, the term congenital cranial dysinnervation disorders (CCDDs) was
      proposed to group heterogeneous syndromes with congenital abnormalities of ocular
      muscle and facial innervations. The concept of neurogenic etiology has been
      supported by discovery of genes that are essential to the normal development of
      brainstem, cranial nerves, and their axonal connections. The CCDDs include Duane
      retraction syndrome, congenital fibrosis of the extraocular muscles, Mobius
      syndrome, horizontal gaze palsy with progressive scoliosis, the human homeobox
      related disorders, pontine cap tegmental dysplasia, and an expanding list. The
      purpose of this review was to update the imaging features, as well as clinical
      and genetic information, regarding cases of CCDDs. 

PMID- 24132068
TI  - Posterior fossa malformation associated with cerebral anomalies: genetic and
      imaging features.
AB  - Many posterior fossa malformations are associated with other malformations
      particularly supratentorial ones, which tend to affect the prognosis of these
      patients. The role of the cerebellum in higher learning is just beginning to be
      understood, but it is obvious that cerebellar abnormalities may result in higher
      cognition defects. Studies have demonstrated cerebellar abnormalities in patients
      with developmental encephalopathies, such as autism, mental retardation, and Rett
      syndrome. Disorders that affect cell life cycles and result in abnormal cell
      proliferation and abnormal cell migration disorders (hemimegalencephaly,
      dystroglicanopathy, lissencephaly, and gray matter heterotopia) can also be
      accompanied by posterior fossa malformations. In this article, we discuss
      hindbrain-midbrain malformations associated with developmental encephalopathies
      and with supratentorial brain abnormalities that result from abnormal cell
      proliferation and cell migration. 

PMID- 24132069
TI  - Neuroimaging of Dandy-Walker malformation: new concepts.
AB  - Dandy-Walker malformation (DWM) is the most common human cerebellar malformation,
      characterized by hypoplasia of the cerebellar vermis, cystic dilation of the
      fourth ventricle, and an enlarged posterior fossa with upward displacement of the
      lateral sinuses, tentorium, and torcular. Although its pathogenesis is not
      completely understood, there are several genetic loci related to DWM as well as
      syndromic malformations and congenital infections. Dandy-Walker malformation is
      associated with other central nervous system abnormalities, including dysgenesis
      of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube
      defects. Hydrocephalus plays an important role in the development of symptoms and
      neurological outcome in patients with DWM, and the aim of surgical treatment is
      usually the control of hydrocephalus and the posterior fossa cyst. Imaging
      modalities, especially magnetic resonance imaging, are crucial for the diagnosis
      of DWM and distinguishing this disorder from other cystic posterior fossa
      lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection
      with cerebrospinal fluid signal intensity and a median line communication with
      the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna
      presents as an extraaxial fluid collection posteroinferior to an intact
      cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar
      hemispheres and the fourth ventricle. Patients with DWM show an enlarged
      posterior fossa filled with a cystic structure that communicates freely with the
      fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is
      of utmost importance for understanding the cerebellar malformations, including
      DWM, and other related entities. 

PMID- 24132070
TI  - Facile preparation of ammonium alginate-derived nanofibers carrying diverse
      therapeutic cargo.
AB  - Alginic acid was converted to a variety of ammonium alginate derivatives carrying
      diverse chemical cargo such as analgesics, antibiotics, and enzymes. These
      functional polymers could be fashioned into nanofibrous mats by electrostatic
      spinning. The therapeutic payload could be released in functional form by a
      simple ion exchange mechanism. Prospects in wound healing are discussed. 

PMID- 24132071
TI  - Switching kinetics of the ferroelectric transition in K2SeO4 studied by
      stroboscopic gamma-ray diffraction.
AB  - The kinetics of the ferroelectric lock-in transition in potassium selenate
      (K2SeO4) was studied on a millisecond timescale using high-resolution gamma-ray
      diffraction. A large change of the line width and wavevector of the first order
      satellite is observed during the switching process. This is attributed to a loss
      of long-range order under the influence of the electric field. In addition, the
      incommensurate phase is stabilized by the pulsed field and the transition to the
      pure commensurate phase is shifted to lower temperatures. Strains that may build
      up during the rapid switching process are supposed to be the reason for this
      behaviour. 

PMID- 24132072
TI  - An Internet-Based Intervention (Condom-Him) to Increase Condom Use Among HIV
      Positive Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: In the recent years, the Internet has been used as a medium to find
      sexual partners and engage in risky sexual behavior. This has changed the way in
      which men having have sex with men (MSM) seek sexual partners and has increased
      the number of high-risk sexual encounters. Therefore, developers of human
      immunodeficiency virus (HIV)-prevention interventions have also started using the
      Internet as a viable medium to promote safe sexual behaviors. However, much of
      the efforts thus far have been aimed at HIV-negative rather than HIV-positive
      MSM. HIV-positive individuals continue to engage in risky sexual behaviors and
      thus constitute an important group in which HIV prevention strategies need to be
      addressed. Therefore, HIV prevention in HIV-positive MSM is a critical issue.
      OBJECTIVE: Condom-Him, an Internet-based intervention tailored to increase condom
      use among HIV-positive MSM, was developed with the aim of improving condom use,
      self-efficacy, and intentions to use condoms among these individuals. The
      acceptability and feasibility of this Internet-based intervention will be
      examined in a pilot study. METHODS: We will perform a randomized controlled
      parallel-group superiority trial. HIV-positive MSM who currently engage in
      unprotected anal sex will be recruited for the study. Participants will be
      randomly assigned using a one-to-one allocation ratio generated by the computer
      program. The researchers will be blinded to participant's group assignment.
      Participants will be assigned either to use the Condom-Him intervention
      (experimental arm) or to view a list of websites containing HIV/AIDS related
      information (control arm). Self-administered questionnaires will be provided
      online before randomization (baseline) and two weeks after intervention (post
      test). RESULTS: The study will include a total of 60 participants with 30 in each
      group. The results from this pilot study will provide further evidence for a
      larger study to examine the effectiveness of this intervention and will provide a
      cost-effective and widely accessible approach to HIV prevention for HIV-positive
      MSM. CONCLUSIONS: Internet-based interventions for HIV-positive MSM, a population
      that has been under-represented in the efforts for positive prevention of HIV
      within Canada, have the potential to provide a cost-effective strategy, which
      influences the way in which information is accessed and provided to high-risk
      individuals. The advantages of an Internet-based intervention include the
      potential to provide consistency in the delivery of an intervention and the
      ability to disseminate the intervention to a wider population. Internet-based
      interventions are perceived as vital tools in combating HIV infection within the
      realm of social media. Therefore, it is important to determine the feasibility
      and acceptability of these interventions before implementing them. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01726153;
      http://clinicaltrials.gov/ct2/show/NCT01726153 (Archived by WebCite at
      http://www.webcitation.org/6Jljzip8B).

PMID- 24132074
TI  - Male breast cancer: 20-year survival data for post-mastectomy radiotherapy.
AB  - BACKGROUND: The goal of this population-based study was to determine the impact
      of post-mastectomy radiation therapy on long-term overall survival (OS) of male
      patients with breast cancer. PATIENTS AND METHODS: We investigated 20-year OS
      rates of 664 patients diagnosed with primary stage I-III breast cancer in former
      East Germany between 1970 and 1989. Patients had a radical mastectomy with
      axillary lymph node dissection without systemic adjuvant therapy. RESULTS: Median
      follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post
      mastectomy radiotherapy. Radiotherapy showed different effects in each stage
      group after 20 years. Whereas there was an OS trend for radiotherapy to harm
      patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval
      (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage
      II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival
      benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95%
      CI 0.41-0.88; p = 0.008). CONCLUSION: Post-mastectomy radiotherapy is associated
      with longer OS in male patients with stage III breast cancer. Male breast cancer
      patients at stages I and II do not seem to benefit from radiotherapy, but
      obsolete irradiation techniques might explain adverse long-term effects in
      earlier stages.

PMID- 24132075
TI  - Species matter: the role of competition in the assembly of congeneric bacteria.
AB  - Interspecific competition is an important driver of community assembly in plants
      and animals, but phylogenetic evidence for interspecific competition in bacterial
      communities has been elusive. This could indicate that other processes such as
      habitat filtering or neutral processes are more important in bacterial community
      assembly. Alternatively, this could be a consequence of the lack of a consistent
      and meaningful species definition in bacteria. We hypothesize that competition in
      bacterial community assembly has gone undetected at least partly because overly
      broad measures of bacterial diversity units were used in previous studies. First,
      we tested our hypothesis in a simulation where we showed that how species are
      defined can dramatically affect whether phylogenetic overdispersion (a signal
      consistent with competitive exclusion) will be detected. Second, we demonstrated
      that using finer-scale Operational Taxonomic Units (OTUs) (with more stringent
      16S rRNA sequence identity cutoffs or based on fast-evolving protein coding
      genes) in natural populations revealed previously undetected overdispersion.
      Finally, we argue that bacterial ecotypes, diversity units incorporating
      ecological and evolutionary theory, are superior to OTUs for the purpose of
      studying community assembly. 

PMID- 24132076
TI  - Seasonal microbial community dynamics correlate with phytoplankton-derived
      polysaccharides in surface coastal waters.
AB  - Phytoplankton produce large amounts of polysaccharide gel material known as
      transparent exopolymer particles (TEP). We investigated the potential links
      between phytoplankton-derived TEP and microbial community structure in the sea
      surface microlayer and underlying water at the English Channel time-series
      station L4 during a spring diatom bloom, and in two adjacent estuaries. Major
      changes in bacterioneuston and bacterioplankton community structure occurred
      after the peak of the spring bloom at L4, and coincided with the significant
      decline of microlayer and water column TEP. Increased abundance of
      Flavobacteriales and Rhodobacterales in bacterioneuston and bacterioplankton
      communities at L4 was significantly related to the TEP decline, indicating that
      both taxa could be responsible. The results suggest that TEP is an important
      factor in determining microbial diversity in coastal waters, and that TEP
      utilisation could be a niche occupied by Flavobacteriales and Rhodobacterales. 

PMID- 24132077
TI  - Spatial heterogeneity and co-occurrence patterns of human mucosal-associated
      intestinal microbiota.
AB  - Human gut microbiota shows high inter-subject variations, but the actual spatial
      distribution and co-occurrence patterns of gut mucosa microbiota that occur
      within a healthy human instestinal tract remain poorly understood. In this study,
      we illustrated a model of this mucosa bacterial communities' biogeography, based
      on the largest data set so far, obtained via 454-pyrosequencing of bacterial 16S
      rDNAs associated with 77 matched biopsy tissue samples taken from terminal ileum,
      ileocecal valve, ascending colon, transverse colon, descending colon, sigmoid
      colon and rectum of 11 healthy adult subjects. Borrowing from macro-ecology, we
      used both Taylor's power law analysis and phylogeny-based beta-diversity metrics
      to uncover a highly heterogeneous distribution pattern of mucosa microbial
      inhabitants along the length of the intestinal tract. We then developed a spatial
      dispersion model with an R-squared value greater than 0.950 to map out the gut
      mucosa-associated flora's non-linear spatial distribution pattern for 51.60% of
      the 188 most abundant gut bacterial species. Furthermore, spatial co-occurring
      network analysis of mucosa microbial inhabitants together with occupancy (that is
      habitat generalists, specialists and opportunist) analyses implies that
      ecological relationships (both oppositional and symbiotic) between mucosa
      microbial inhabitants may be important contributors to the observed spatial
      heterogeneity of mucosa microbiota along the human intestine and may even
      potentially be associated with mutual cooperation within and functional stability
      of the gut ecosystem.

PMID- 24132078
TI  - Using environmental niche models to test the 'everything is everywhere'
      hypothesis for Badhamia.
AB  - It is often discussed whether the biogeography of free-living protists is better
      explained by the 'everything is everywhere'(EiE) hypothesis, which postulates
      that only ecology drives their distribution, or by the alternative hypothesis of
      'moderate endemicity' in which geographic barriers can limit their dispersal. To
      formally test this, it would be necessary not only to find organisms restricted
      to a geographical area but also to check for their presence in any other place
      with a similar ecology. We propose the use of environmental niche models to
      generate and test null EiE distributions. Here we have analysed the distribution
      of 18S rDNA variants (ribotypes) of the myxomycete Badhamia melanospora
      (belonging to the protozoan phylum Amoebozoa) using 125 specimens from 91
      localities. Two geographically structured groups of ribotypes congruent with
      slight morphological differences in the spores can be distinguished. One group
      comprises all populations from Argentina and Chile, and the other is formed by
      populations from North America together with human-introduced populations from
      other parts of the world. Environmental climatic niche models constructed
      separately for the two groups have significant differences, but show several
      overlapping areas. However, only specimens from one group were found in an
      intensively surveyed area in South America where both niche models overlap. It
      can be concluded that everything is not everywhere for B. melanospora. This taxon
      constitutes a complex formed by at least two cryptic species that probably
      diverged allopatrically in North and South America.

PMID- 24132079
TI  - Fish gut microbiota analysis differentiates physiology and behavior of invasive
      Asian carp and indigenous American fish.
AB  - Gut microbiota of invasive Asian silver carp (SVCP) and indigenous planktivorous
      gizzard shad (GZSD) in Mississippi river basin were compared using 16S rRNA gene
      pyrosequencing. Analysis of more than 440 000 quality-filtered sequences obtained
      from the foregut and hindgut of GZSD and SVCP revealed high microbial diversity
      in these samples. GZSD hindgut (GZSD_H) samples (n=23) with >7000 operational
      taxonomy units (OTUs) exhibited the highest alpha-diversity indices followed by
      SVCP foregut (n=15), GZSD foregut (n=9) and SVCP hindgut (SVCP_H) (n=24). UniFrac
      distance-based non-metric multidimensional scaling (NMDS) analysis showed that
      the microbiota of GZSD_H and SVCP_H were clearly separated into two clusters:
      samples in the GZSD cluster were observed to vary by sampling location and
      samples in the SVCP cluster by sampling date. NMDS further revealed distinct
      microbial community between foregut to hindgut for individual GZSD and SVCP.
      Cyanobacteria, Proteobacteria, Actinobacteria and Bacteroidetes were detected as
      the predominant phyla regardless of fish or gut type. The high abundance of
      Cyanobacteria observed was possibly supported by their role as the fish's major
      food source. Furthermore, unique and shared OTUs and OTUs in each gut type were
      identified, three OTUs from the order Bacteroidales, the genus Bacillariophyta
      and the genus Clostridium were found significantly more abundant in GZSD_H (14.9
      22.8%) than in SVCP_H (0.13-4.1%) samples. These differences were presumably
      caused by the differences in the type of food sources including bacteria
      ingested, the gut morphology and digestion, and the physiological behavior
      between GZSD and SVCP. 

PMID- 24132080
TI  - Genetic diversity of inorganic carbon uptake systems causes variation in CO2
      response of the cyanobacterium Microcystis.
AB  - Rising CO2 levels may act as an important selective factor on the CO2
      concentrating mechanism (CCM) of cyanobacteria. We investigated genetic diversity
      in the CCM of Microcystis aeruginosa, a species producing harmful cyanobacterial
      blooms in many lakes worldwide. All 20 investigated Microcystis strains contained
      complete genes for two CO2 uptake systems, the ATP-dependent bicarbonate uptake
      system BCT1 and several carbonic anhydrases (CAs). However, 12 strains lacked
      either the high-flux bicarbonate transporter BicA or the high-affinity
      bicarbonate transporter SbtA. Both genes, bicA and sbtA, were located on the same
      operon, and the expression of this operon is most likely regulated by an
      additional LysR-type transcriptional regulator (CcmR2). Strains with only a small
      bicA fragment clustered together in the phylogenetic tree of sbtAB, and the bicA
      fragments were similar in strains isolated from different continents. This
      indicates that a common ancestor may first have lost most of its bicA gene and
      subsequently spread over the world. Growth experiments showed that strains with
      sbtA performed better at low inorganic carbon (Ci) conditions, whereas strains
      with bicA performed better at high Ci conditions. This offers an alternative
      explanation of previous competition experiments, as our results reveal that the
      competition at low CO2 levels was won by a specialist with only sbtA, whereas a
      generalist with both bicA and sbtA won at high CO2 levels. Hence, genetic and
      phenotypic variation in Ci uptake systems provide Microcystis with the potential
      for microevolutionary adaptation to changing CO2 conditions, with a selective
      advantage for bicA-containing strains in a high-CO2 world. 

PMID- 24132081
TI  - Seasonal variation in the metatranscriptomes of a Thaumarchaeota population from
      SE USA coastal waters.
AB  - We used a combination of metatranscriptomic analyses and quantitative PCR (qPCR)
      to study seasonal changes in Thaumarchaeota populations from a salt marsh
      dominated estuary. Surface waters (0.5 m depth) were sampled quarterly at Marsh
      Landing, Sapelo Island, GA, USA over a 3-year period. We found a mid-summer peak
      in Thaumarchaeota abundance measured by qPCR of either 16S rRNA or amoA genes in
      each of the 3 years. Thaumarchaeota were 100-1000-fold more abundant during the
      peak than at other times of the year, whereas the abundance of ammonia- and
      nitrite-oxidizing Bacteria varied <10-fold over the same period. Analysis of the
      microdiversity of several highly transcribed genes in 20 metatranscriptomes from
      a 1-year subset of these samples showed that the transcriptionally active
      population consisted of 2 or 3 dominant phylotypes that differed between
      successive summers. This shift appeared to have begun during the preceding winter
      and spring. Transcripts from the same genes dominated the Thaumarchaeota mRNA
      pool throughout the year, with genes encoding proteins believed to be involved in
      nitrogen uptake and oxidation, and two hypothetical proteins being the most
      abundant transcripts in all libraries. Analysis of individual genes over the
      seasonal cycle suggested that transcription was tied more closely to variation in
      growth rates than to seasonal changes in environmental conditions. Day-night
      differences in the relative abundance of transcripts for ribosomal proteins
      suggested diurnal variation in Thaumarchaeota growth. 

PMID- 24132083
TI  - Evaluation of a passive sampler for the speciation of metals in urban runoff
      water.
AB  - Metals in urban runoff water need to be monitored in order to estimate fluxes and
      assess their impact on the aquatic environment. Passive sampling is a useful and
      reliable emerging tool for measuring time averaged concentrations of metals in
      water bodies. This paper describes the deployment of a passive sampler to measure
      Cu, Ni and Zn in an urban runoff water treatment facility. The concentrations
      derived from the passive samplers are compared to concentrations obtained from an
      automated water sampler which provides pooled spot water samples and to model
      predictions from the visualMINTEQ computer speciation code. Results show that
      visualMINTEQ predictions partly describe the metal speciation in non-equilibrium
      systems. In addition we conclude that passive samplers are useful for monitoring
      and characterization of metal speciation under chemodynamic conditions. 

PMID- 24132082
TI  - Retained asymptomatic third molars and risk for second molar pathology.
AB  - Prophylactic extraction of unerupted asymptomatic third molars is the most common
      oral surgery procedure in the United States. However, limited evidence exists to
      justify its costs and associated morbidity. We analyzed data collected over 25
      years from 416 adult men enrolled in the Veterans Affairs Dental Longitudinal
      Study to evaluate the association of retained asymptomatic third molars with risk
      of adjacent second molar pathology (caries and/or periodontitis), based on third
      molar status (i.e., absent, erupted, or unerupted). Unerupted molars were further
      categorized as either "soft tissue" or "bony" impacted. We found that the lowest
      prevalence and incidence of second molar pathology occurred when the adjacent
      third molar was absent. The presence of a third molar that was soft tissue
      impacted increased the risk of incident second molar pathology 4.88-fold (95%
      confidence interval: 2.62, 9.08). Having an erupted or "bony" impacted third
      molar increased the risk of incident second molar pathology by 1.74 (95%
      confidence interval: 1.34, 2.25) and 2.16 (95% confidence interval: 1.56, 2.99),
      respectively. The retention of third molars is associated with increased risk of
      second molar pathology in middle-aged and older adult men. 

PMID- 24132084
TI  - The influences of computer system success and informatics competencies on
      organizational impact in nursing environments.
AB  - The previous literature provides evidence that the characteristics of a
      successful computer system and the informatics competencies of individuals play a
      critical role in the adoption of information technology. However, while the
      combined effects of the two may provide a comprehensive view in understanding
      nursing informatics research, they have rarely been studied simultaneously.
      Therefore, this study aimed to examine the influences of computer system success
      and informatics competencies on nursing organizational impact. We surveyed 454
      nurses who worked at international patient centers in Taiwan. The results show
      that both nurses' informatics competencies and nursing computer system success do
      have influence on nursing organizational impact. Moreover, nurses' informatics
      competencies have a greater effect than the superior characteristics of a nursing
      computer system on nursing organizational performance. Finally, implications for
      practitioners complete this study. 

PMID- 24132086
TI  - Imprinted green beards: a little less than kin and more than kind.
AB  - RNA is complementary to the DNA sequence from which it is transcribed. Therefore,
      interactions between DNA and RNA provide a simple mechanism of genetic self
      detection within nuclei. Imprinted RNAs could enable alleles of maternal and
      paternal origin to detect whether they are the same (homozygous) or different
      (heterozygous), and thereby provide strategic information about expected
      relatedness to siblings. 

PMID- 24132087
TI  - Kin selection, genomics and caste-antagonistic pleiotropy.
AB  - Kin selection is a fundamentally important process that affects the evolution of
      social behaviours. The genomics revolution now provides the opportunity to test
      kin selection theory using genomic data. In this commentary, we discuss previous
      studies that explored the link between kin selection and patterns of variation
      within the genome. We then present a new theory aimed at understanding the
      evolution of genes involved in the development of social insects. Specifically,
      we investigate caste-antagonistic pleiotropy, which occurs when the phenotypes of
      distinct castes are optimized by different genotypes at a single locus. We find
      that caste-antagonistic pleiotropy leads to narrow regions where polymorphism can
      be maintained. Furthermore, multiple mating by queens reduces the region in which
      worker-favoured alleles fix, which suggests that multiple mating impedes worker
      caste evolution. We conclude by discussing ways to test these and other facets of
      kin selection using newly emerging genomic data. 

PMID- 24132088
TI  - Towards greater realism in inclusive fitness models: the case of worker
      reproduction in insect societies.
AB  - The conflicts over sex allocation and male production in insect societies have
      long served as an important test bed for Hamilton's theory of inclusive fitness,
      but have for the most part been considered separately. Here, we develop new
      coevolutionary models to examine the interaction between these two conflicts and
      demonstrate that sex ratio and colony productivity costs of worker reproduction
      can lead to vastly different outcomes even in species that show no variation in
      their relatedness structure. Empirical data on worker-produced males in eight
      species of Melipona bees support the predictions from a model that takes into
      account the demographic details of colony growth and reproduction. Overall, these
      models contribute significantly to explaining behavioural variation that previous
      theories could not account for. 

PMID- 24132089
TI  - Hamiltonian inclusive fitness: a fitter fitness concept.
AB  - In 1963-1964 W. D. Hamilton introduced the concept of inclusive fitness, the only
      significant elaboration of Darwinian fitness since the nineteenth century. I
      discuss the origin of the modern fitness concept, providing context for
      Hamilton's discovery of inclusive fitness in relation to the puzzle of altruism.
      While fitness conceptually originates with Darwin, the term itself stems from
      Spencer and crystallized quantitatively in the early twentieth century.
      Hamiltonian inclusive fitness, with Price's reformulation, provided the solution
      to Darwin's 'special difficulty'-the evolution of caste polymorphism and
      sterility in social insects. Hamilton further explored the roles of inclusive
      fitness and reciprocation to tackle Darwin's other difficulty, the evolution of
      human altruism. The heuristically powerful inclusive fitness concept ramified
      over the past 50 years: the number and diversity of 'offspring ideas' that it has
      engendered render it a fitter fitness concept, one that Darwin would have
      appreciated. 

PMID- 24132090
TI  - The veil of ignorance can favour biological cooperation.
AB  - Lack of information is a constraint but ignorance can sometimes assist the
      evolution of cooperation by constraining selfishness. We discuss examples
      involving both ignorance of role or pay-off and ignorance of relatedness.
      Ignorance can favour cooperative traits like grouping and warning coloration and
      reduce conflicts from meiotic drive, imprinting, greenbeards and various forms of
      nepotism. 

PMID- 24132091
TI  - Parasites and altruism: converging roads.
AB  - W.D. Hamilton was most known for his work on two topics: social evolution and
      parasites. Although at first glance these seem to be disparate interests, they
      share many attributes and have logical connections within evolutionary biology.
      Nevertheless, Hamilton's contributions in these areas met with very different
      receptions, with his place in the field of social evolution assured, but his work
      on the role of parasites perceived as more specialized. We take an historical
      approach to examine the reasons for this difference. 

PMID- 24132092
TI  - Genes underlying altruism.
AB  - William D. Hamilton postulated the existence of 'genes underlying altruism',
      under the rubric of inclusive fitness theory, a half-century ago. Such genes are
      now poised for discovery. In this article, we develop a set of intuitive criteria
      for the recognition and analysis of genes for altruism and describe the first
      candidate genes affecting altruism from social insects and humans. We also
      provide evidence from a human population for genetically based trade-offs,
      underlain by oxytocin-system polymorphisms, between alleles for altruism and
      alleles for non-social cognition. Such trade-offs between self-oriented and
      altruistic behaviour may influence the evolution of phenotypic diversity across
      all social animals. 

PMID- 24132093
TI  - Dissecting ant recognition systems in the age of genomics.
AB  - Hamilton is probably best known for his seminal work demonstrating the role of
      kin selection in social evolution. His work made it clear that, for individuals
      to direct their altruistic behaviours towards appropriate recipients (kin),
      mechanisms must exist for kin recognition. In the social insects, colonies are
      typically comprised of kin, and colony recognition cues are used as proxies for
      kinship cues. Recent years have brought rapid advances in our understanding of
      the genetic and molecular mechanisms that are used for this process. Here, I
      review some of the most notable advances, particularly the contributions from
      recent ant genome sequences and molecular biology. 

PMID- 24132094
TI  - Nice to kin and nasty to non-kin: revisiting Hamilton's early insights on
      eusociality.
AB  - When helping behaviour is costly, Hamiltonian logic implies that animals need to
      direct helpful acts towards kin, so that indirect fitness benefits justify the
      costs. We revisit inferences about nepotism and aggression in Hamilton's 1964
      paper to argue that he overestimated the general significance of nepotism, but
      that other issues that he raised continue to suggest novel research agendas
      today. We now know that nepotism in eusocial insects is rare, because variation
      in genetic recognition cues is insufficient. A lower proportion of individuals
      breeding and larger clutch sizes selecting for a more uniform colony odour may
      explain this. Irreversible worker sterility can induce both the fiercest possible
      aggression and the highest likelihood of helping random distant kin, but these
      Hamiltonian contentions still await large-scale testing in social animals. 

PMID- 24132095
TI  - Kinship and the evolution of social behaviours in the sea.
AB  - Until recently, little attention has been paid to the existence of kin structure
      in the sea, despite the fact that many marine organisms are sessile or sedentary.
      This lack of attention to kin structure, and its impacts on social evolution,
      historically stems from the pervasive assumption that the dispersal of gametes
      and larvae is almost always sufficient to prevent any persistent associations of
      closely related offspring or adults. However, growing evidence, both theoretical
      and empirical, casts doubt on the generality of this assumption, not only in
      species with limited dispersal, but also in species with long dispersive phases.
      Moreover, many marine organisms either internally brood their progeny or package
      them in nurseries, both of which provide ample opportunities for kinship to
      influence the nature and outcomes of social interactions among family members. As
      the evidence for kin structure within marine populations mounts, it follows that
      kin selection may play a far greater role in the evolution of both behaviours and
      life histories of marine organisms than is presently appreciated. 

PMID- 24132096
TI  - Kin selection, species richness and community.
AB  - Can evolutionary and ecological dynamics operating at one level of the biological
      hierarchy affect the dynamics and structure at other levels? In social insects,
      strong hostility towards unrelated individuals can evolve as a kin-selected
      counter-adaptation to intraspecific social parasitism. This aggression in turn
      might cause intraspecific competition to predominate over interspecific
      competition, permitting coexistence with other social insect species. In other
      words, kin selection-a form of intra-population dynamics-might enhance the
      species richness of the community, a higher-level structure. The converse effect,
      from higher to lower levels, might also operate, whereby strong interspecific
      competition may limit the evolution of selfish individual traits. If the latter
      effect were to prove more important, it would challenge the common view that
      intra-population dynamics (via individual or gene selection) is the main driver
      of evolution. 

PMID- 24132097
TI  - Size and accumulation of fuel reserves at stopover predict nocturnal restlessness
      in a migratory bird.
AB  - Early arrival at the breeding site positively affects the breeding success of
      migratory birds. During migration, birds spend most of their time at stopovers.
      Therefore, determining which factors shape stopover duration is essential to our
      understanding of avian migration. Because the main purpose of stopover is to
      accumulate fat as fuel for the next flight bout, fuel reserves at arrival and the
      accumulation of fuel are both expected to affect stopover departure decisions.
      Here, we determined whether fuel reserves and fuel accumulation predict a bird's
      motivation to depart, as quantified by nocturnal migratory restlessness
      (Zugunruhe), using northern wheatears (Oenanthe oenanthe) that were captured and
      temporarily contained at spring stopover. We found that fuel reserves at capture
      were positively correlated with Zugunruhe, and negatively correlated with fuel
      accumulation. This indicates that fat birds were motivated to depart, whereas
      lean birds were set on staying and accumulating fuel. Moreover, the change in
      fuel reserves was positively correlated with the concurrent change in Zugunruhe,
      providing the first empirical evidence for a direct link between fuel
      accumulation and Zugunruhe during stopover. Our study indicates that, together
      with innate rhythms and weather, the size and accumulation of fuel reserves shape
      stopover duration, and hence overall migration time. 

PMID- 24132098
TI  - To call or not to call: parents assess the vulnerability of their young before
      warning them about predators.
AB  - Communication about predators can reveal the effects of both conspecific and
      heterospecific audiences on signalling strategy, providing insight into signal
      function and animal cognition. In species that alarm call to their young, parents
      face a fundamental dilemma: calling can silence noisy offspring and so make them
      less likely to be overheard, but can also alert predators that young are nearby.
      Parents could resolve this dilemma by being sensitive to the current
      vulnerability of offspring, and calling only when young are most at risk. Testing
      whether offspring vulnerability affects parental strategy has proved difficult,
      however, because more vulnerable broods are often also more valuable. We tested
      experimentally whether parent white-browed scrubwren, Sericornis frontalis,
      assessed brood noisiness when alarm calling near nests. When a model predator was
      nearby, parents gave more alarm calls when playbacks simulated noisy broods, yet
      brood noisiness did not affect adult calling when only a control model was
      present. Parents were therefore sensitive to the tradeoff between silencing young
      and alerting predators to the presence of nests. Our study demonstrates that
      receiver vulnerability can affect signalling decisions in species other than
      primates. 

PMID- 24132099
TI  - Embryonic growth and antioxidant provision in avian eggs.
AB  - Avian embryos undergo extremely rapid development over a relatively short period
      of time, and so are likely to suffer high levels of oxidative damage unless this
      is mitigated by sufficient maternal allocation of appropriate antioxidants. At a
      species level, it is therefore predicted that antioxidants should be allocated to
      eggs according to the rate of embryonic growth, such that eggs containing embryos
      that grow faster are furnished with higher antioxidant levels, independent of egg
      size. We tested this prediction for three potentially important classes of
      dietary-derived yolk antioxidants: carotenoids, vitamin E and vitamin A. Across
      species, we found positive relationships between embryonic growth rate and total
      yolk levels of each of the three antioxidant classes. Moreover, there were
      consistent differences in antioxidant provision between pairs of species that
      share a common initial egg mass yet have differing rates of embryonic growth,
      such that the eggs of the faster-developing species have higher levels of
      carotenoids and vitamin E. These results may explain the marked interspecific
      variation in antioxidant provision and provide evidence for the role that these
      antioxidants play during embryonic development. 

PMID- 24132100
TI  - 50 Years on: the legacy of William Donald Hamilton.

PMID- 24132101
TI  - Local shear viscosity of strongly inhomogeneous dense fluids: from the hard
      sphere to the Lennard-Jones fluids.
AB  - This work aims at providing a tractable approach to model the local shear
      viscosity of strongly inhomogeneous dense fluids composed of spherical molecules,
      in which the density variations occur on molecular distance. The proposed scheme,
      which relies on the local density average model, has been applied to the quasi
      hard-sphere, the Week-Chandler-Andersen and the Lennard-Jones fluids. A weight
      function has been developed to deal with the hard-sphere fluid given the
      specificities of momentum exchange. To extend the approach to the smoothly
      repulsive potential, we have taken into account that the non-local contributions
      to the viscosity due to the interactions of particles separated by a given
      distance are temperature dependent. Then, using a simple perturbation scheme, the
      approach is extended to the Lennard-Jones fluids. It is shown that the viscosity
      profiles of inhomogeneous dense fluids deduced from this approach are consistent
      with those directly computed by non-equilibrium molecular dynamics simulations. 

PMID- 24132102
TI  - Tumour microenvironment: To me, to you.

PMID- 24132104
TI  - Tyrosine kinase gene rearrangements in epithelial malignancies.
AB  - Chromosomal rearrangements that lead to oncogenic kinase activation are observed
      in many epithelial cancers. These cancers express activated fusion kinases that
      drive the initiation and progression of malignancy, and often have a considerable
      response to small-molecule kinase inhibitors, which validates these fusion
      kinases as 'druggable' targets. In this Review, we examine the aetiologic,
      pathogenic and clinical features that are associated with cancers harbouring
      oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and
      RET. We discuss the clinical outcomes with targeted therapies and explore
      strategies to discover additional kinases that are activated by chromosomal
      rearrangements in solid tumours. 

PMID- 24132108
TI  - Metabolism: IDH2 drives cancer in vivo.

PMID- 24132114
TI  - Successful treatment of acute thrombotic microangiopathy by eculizumab after
      combined lung and kidney transplantation.

PMID- 24132110
TI  - The roles of TGFbeta in the tumour microenvironment.
AB  - The influence of the microenvironment on tumour progression is becoming clearer.
      In this Review we address the role of an essential signalling pathway, that of
      transforming growth factor-beta, in the regulation of components of the tumour
      microenvironment and how this contributes to tumour progression. 

PMID- 24132115
TI  - Splenunculus masquerading as a neuroendocrine tumor of the pancreatic allograft
      in a kidney-pancreas recipient.

PMID- 24132116
TI  - Elevated everolimus levels during severe diarrhea in two children after heart
      transplantation.

PMID- 24132111
TI  - The microbiome and cancer.
AB  - Microbiota and host form a complex 'super-organism' in which symbiotic
      relationships confer benefits to the host in many key aspects of life. However,
      defects in the regulatory circuits of the host that control bacterial sensing and
      homeostasis, or alterations of the microbiome, through environmental changes
      (infection, diet or lifestyle), may disturb this symbiotic relationship and
      promote disease. Increasing evidence indicates a key role for the bacterial
      microbiota in carcinogenesis. In this Opinion article, we discuss links between
      the bacterial microbiota and cancer, with a particular focus on immune responses,
      dysbiosis, genotoxicity, metabolism and strategies to target the microbiome for
      cancer prevention. 

PMID- 24132117
TI  - Successful kidney transplantation from a brain-dead donor with ornithine
      transcarbamylase deficiency.

PMID- 24132118
TI  - Mycobacterium genavense and chronic intermittent diarrhea in a kidney and
      pancreas transplant recipient.

PMID- 24132119
TI  - Intestinal microsporidiosis due to Enterocytozoon bieneusi in a pediatric kidney
      transplant recipient successfully treated with fumagillin.

PMID- 24132120
TI  - The first venomous crustacean revealed by transcriptomics and functional
      morphology: remipede venom glands express a unique toxin cocktail dominated by
      enzymes and a neurotoxin.
AB  - Animal venoms have evolved many times. Venomous species are especially common in
      three of the four main groups of arthropods (Chelicerata, Myriapoda, and
      Hexapoda), which together represent tens of thousands of species of venomous
      spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their
      great diversity of body plans, there is no unambiguous evidence that any
      crustacean is venomous. We provide the first conclusive evidence that the
      aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that
      venoms evolved in all four major arthropod groups. We produced a three
      dimensional reconstruction of the venom delivery apparatus of the remipede
      Speleonectes tulumensis, showing that remipedes can inject venom in a controlled
      manner. A transcriptomic profile of its venom glands shows that they express a
      unique cocktail of transcripts coding for known venom toxins, including a
      diversity of enzymes and a probable paralytic neurotoxin very similar to one
      described from spider venom. We screened a transcriptomic library obtained from
      whole animals and identified a nontoxin paralog of the remipede neurotoxin that
      is not expressed in the venom glands. This allowed us to reconstruct its probable
      evolutionary origin and underlines the importance of incorporating data derived
      from nonvenom gland tissue to elucidate the evolution of candidate venom
      proteins. This first glimpse into the venom of a crustacean and primitively
      aquatic arthropod reveals conspicuous differences from the venoms of other
      predatory arthropods such as centipedes, scorpions, and spiders and contributes
      valuable information for ultimately disentangling the many factors shaping the
      biology and evolution of venoms and venomous species. 

PMID- 24132121
TI  - Performance of standard and stochastic branch-site models for detecting positive
      selection among coding sequences.
AB  - The branch-site model is a widely popular approach that accommodates for the
      lineage- and the site-specific heterogeneity of natural selection regimes among
      coding sequences. This model relies on prior knowledge of the (foreground)
      lineage(s) evolving under positive selection at some sites. Unfortunately, such
      prior information is not always available in practice. A more recent technique
      (Guindon S, Rodrigo A, Dyer K, Huelsenbeck J. 2004. Modeling the site-specific
      variation of selection patterns along lineages. Proc Natl Acad Sci USA 101:12957
      12962) alleviates this issue by explicitly modeling the variability of selection
      patterns using a stochastic process. However, the performance of this approach
      for deciding whether a set of homologous sequences evolved under positive
      selection at some point has not been assessed yet. This study compares the
      sensitivity and specificity of tests for positive selection derived from both the
      standard and the stochastic approaches using extensive simulations. We show that
      the two methods have low proportions of type I errors, that is, they tend to be
      conservative when testing the null hypothesis of no positive selection if
      sequences truly evolve under neutral or negative selection regimes. Also, the
      standard approach is more powerful than the stochastic one when the prior
      knowledge on foreground lineages is correct. When this prior is incorrect,
      however, the stochastic approach outperforms the standard model in a broad range
      of conditions. Additional comparisons also suggest that the stochastic branch
      site method compares favorably with the recently proposed mixed-effects model of
      evolution of Murrell et al. (Murrell B, Wertheim JO, Moola S, Weighill T,
      Scheffler K, Pond SLK. 2012. Detecting individual sites subject to episodic
      diversifying selection. PLoS Genet. 8:e1002764). Altogether, our results show
      that the standard branch-site model is well suited to confirmatory analyses,
      whereas the stochastic approach should be preferred over the standard or the
      mixed-effects ones for exploratory studies. 

PMID- 24132122
TI  - MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.
AB  - We announce the release of an advanced version of the Molecular Evolutionary
      Genetics Analysis (MEGA) software, which currently contains facilities for
      building sequence alignments, inferring phylogenetic histories, and conducting
      molecular evolutionary analysis. In version 6.0, MEGA now enables the inference
      of timetrees, as it implements the RelTime method for estimating divergence times
      for all branching points in a phylogeny. A new Timetree Wizard in MEGA6
      facilitates this timetree inference by providing a graphical user interface (GUI)
      to specify the phylogeny and calibration constraints step-by-step. This version
      also contains enhanced algorithms to search for the optimal trees under
      evolutionary criteria and implements a more advanced memory management that can
      double the size of sequence data sets to which MEGA can be applied. Both GUI and
      command-line versions of MEGA6 can be downloaded from www.megasoftware.net free
      of charge. 

PMID- 24132123
TI  - Efficient colorimetric and fluorescent detection of fluoride in DMSO-water
      mixtures with arylaldoximes.
AB  - Fluoride detection through hydrogen bonding or deprotonation is most commonly
      achieved using amide, urea or pyrrole derivatives. The sensor molecules are often
      complex constructs and several synthetic steps are required for their
      preparation. Here we report the discovery that simple arylaldoximes have
      remarkable properties as fluoride anion sensors, providing distinct colorimetric
      or fluorescent readouts, depending on the structure of the arylaldoxime. The
      oximes showed exceptional selectivity towards fluoride over other typical anions,
      and low detection limits for fluoride in both DMSO and DMSO-water mixtures were
      obtained. 

PMID- 24132124
TI  - Y-chromosome diversity in the Kalmyks at the ethnical and tribal levels.
AB  - The Mongolic-speaking Kalmyks currently inhabiting the steppes of the Volga
      region have Central Asian ancestry and are organized into the tribal groups. The
      genetic relationships among these tribes and their origin have remained obscure.
      We analyzed 17 short tandem repeat and 44 binary polymorphisms of Y-chromosome in
      426 individuals mainly from three major tribes of the Kalmyks (the Torguuds,
      Dorwods and Khoshuuds). Among these tribes, the Dorwods and Torguuds, as well as
      the Kalmyks collectively as an ethnic group, showed relatively close genetic
      affinities to each other and to the Mongols and Altaian Kazakhs, whereas the
      Khoshuuds were clearly separated from all of them, gathering with the Manchu,
      Tibetans or Evenks (depending on the algorithm used to calculate genetic
      distances). The genetic results also indicate that paternal gene flow from East
      Europeans to the Kalmyks is very little, despite their cohabitation in the North
      Caspian Steppe during the last 380 years. The occurrence of unique cluster of N1c
      Tat haplotypes in the Khoshuuds, which dates to about 340 years and is likely to
      have East European ancestry, is considered as a result of interethnic contacts
      occurred soon after the appearance of the Kalmyk tribes in the Volga-Ural region.

PMID- 24132125
TI  - A novel break point of the BMPR2 gene exonic deletion in a patient with pulmonary
      arterial hypertension.
AB  - The presence of genetic rearrangements of bone morphogenetic protein type 2
      receptor (BMPR2) was identified in pulmonary arterial hypertension (PAH) patients
      as the deletion or duplication of one or more exons of the gene. We recently
      investigated the deletion break points in exonic deletions of BMPR2 in two
      Japanese familial cases with PAH, and found that these were Alu-mediated via
      either non-allelic homologous recombination or non-homologous recombination. We
      herein report the third case of exonic deletion, which was in a 25-year-old
      female PAH patient with a deletion of BMPR2 exon 3. The break point in this case
      was not located in an Alu sequence. The 5'- and 3'-break point maps between the
      inverted Alu sequences in intron 2 and in exon 3, respectively, resulted in a 759
      bp deletion. This novel exonic deletion in this PAH case may be a unique and non
      recurrent rearrangement, and appears to be of a different size from that in other
      patients. 

PMID- 24132126
TI  - Orientational order-dependent thermal expansion and compressibility of ZrW2O8 and
      ZrMo2O8.
AB  - The role of MO4 (M = W, Mo) orientational disorder in the thermal expansion and
      compressibility of ZrW2O8 and ZrMo2O8 was investigated via in situ powder X-ray
      diffraction at elevated temperature and pressure. A dramatic reduction in the
      bulk modulus of alpha-ZrW2O8, which has ordered WO4 tetrahedra at room
      temperature, from 65 GPa at room temperature to 47 GPa at 386 K was observed to
      be concomitant with the onset of a reversible WO4 orientational disordering upon
      compression. Additionally, the coefficient of thermal expansion (CTE) of the
      alpha phase became more negative upon compression within the temperature range in
      which pressure-dependent disorder was observed; alphal, over the range 298 to 386
      K, was ~-11 ppm K(-1) at 35 MPa but ~-16 ppm K(-1) at 276 MPa. No softening upon
      heating or change in CTE upon compression was observed for ZrW2O8 above the order
      -> disorder phase transition temperature. Cubic ZrMo2O8 has a disordered
      arrangement of MoO4 tetrahedra at all temperatures and pressures accessed in this
      study. Its bulk modulus was independent of temperature, and its CTE was
      insensitive to pressure, much like beta-ZrW2O8. The stability/metastability of
      the cubic and orthorhombic phases upon heating above room temperature and
      compression is discussed, with a focus on changes in the thermodynamics and
      kinetics of the cubic <-> orthorhombic transition.

PMID- 24132127
TI  - Three years (2008-2010) of measurements of atmospheric concentrations of
      organochlorine pesticides (OCPs) at Station Nord, North-East Greenland.
AB  - Atmospheric concentrations of organochlorine pesticides (OCPs) have been measured
      for the first time at Station Nord, North-East Greenland, from 2008 to 2010. The
      data obtained are reported here. Hexachlorobenzene (HCB), endosulfan I and
      hexachlorocyclohexanes (HCHs) were the predominant compounds detected in the
      atmosphere, followed by p,p'-DDE and dieldrin. Chlordane isomers and related
      compounds (trans- and cis-chlordanes, heptachlor and heptachlor epoxide, trans-
      and cis-nonachlor) were also detected. Atmospheric concentrations of the
      investigated compounds were correlated with temperature using the Clausius
      Clapeyron equation in order to obtain information about their transport
      properties. The correlation between atmospheric concentrations and temperature
      was not significant for endosulfan I, gamma-HCH and p,p'-DDT, which indicates
      that direct transport from direct sources is the dominating transport mechanism
      for these compounds. A significant correlation with temperature was found for all
      the other studied pesticides and pesticide degradation products, which indicates
      that re-emission of these compounds from previously contaminated surfaces is an
      important factor for the observed variation in concentrations. Pesticide
      concentrations were also correlated with sea ice cover. Concentrations of the
      compounds that have not been in use for decades correlated with temperature and
      ice cover, while concentrations of compounds still in use did not correlate with
      either of these parameters. These observations indicate that processes such as
      revolatilization from the open sea surface are important mediating factors in the
      dynamics of anthropogenic persistent pollutants in the Arctic environment under
      the expected influence of climate change processes. 

PMID- 24132129
TI  - Brain injury as a risk factor for fever upon admission to the intensive care unit
      and association with in-hospital case fatality: a matched cohort study.
AB  - PURPOSE: To test the hypothesis that fever was more frequent in critically ill
      patients with brain injury when compared to nonneurological patients and to study
      its effect on in-hospital case fatality. METHODS: Retrospective matched cohort
      study utilizing a single-center prospectively compiled registry. Critically ill
      neurological patients >=18 years and consecutively admitted to the intensive care
      unit (ICU) with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and
      traumatic brain injury (TBI) were selected. Patients were matched by sex, age,
      and Acute Physiology and Chronic Health Evaluation II (APACHE-II) to a cohort of
      nonneurological patients. Fever was defined as any temperature >=37.5 degrees C
      within the first 24 hours upon admission to the ICU. The primary outcome measure
      was in-hospital case fatality. RESULTS: Mean age among neurological patients was
      65.6 +/- 15 years, 46% were men, and median APACHE-II was 15 (interquartile range
      11-20). There were 18% AIS, 27% ICH, and 6% TBI. More neurological patients
      experienced fever than nonneurological patients (59% vs 47%, P = .007). The mean
      hospital length of stay was higher for nonneurological patients (18 +/- 20 vs 14
      +/- 15 days, P = .007), and more neurological patients were dead at hospital
      discharge (29% vs 20%, P < .0001). After risk factor adjustment, diagnosis
      (neurological vs nonneurological), and the probability of being exposed to fever
      (propensity score), the following variables were associated with higher in
      hospital case fatality: APACHE-II, neurological diagnosis, mean arterial
      pressure, cardiovascular and respiratory dysfunction in ICU, and fever (odds
      ratio 1.9, 95% confidence interval 1.04-3.6, P = .04). CONCLUSION: These data
      suggest that fever is a frequent occurrence after brain injury, and that it is
      independently associated with in-hospital case fatality.

PMID- 24132131
TI  - Different genetic factors influence specific symptom dimensions of DSM-IV major
      depression.

PMID- 24132132
TI  - Children conceived following induced ovulation or intrauterine insemination have
      a small increased risk of mental disorders.

PMID- 24132133
TI  - The natural history of IgE-mediated food allergy: can skin prick tests and serum
      specific IgE predict the resolution of food allergy?
AB  - IgE-mediated food allergy is a transient condition for some children, however
      there are few indices to predict when and in whom food allergy will resolve. Skin
      prick test (SPT) and serum-specific IgE levels (sIgE) are usually monitored in
      the management of food allergy and are used to predict the development of
      tolerance or persistence of food allergy. The aim of this article is to review
      the published literature that investigated the predictive value of SPT and sIgE
      in development of tolerance in children with a previous diagnosis of peanut, egg
      and milk allergy. A systematic search identified twenty-six studies, of which
      most reported SPT or sIgE thresholds which predicted persistent or resolved
      allergy. However, results were inconsistent between studies. Previous research
      was hampered by several limitations including the absence of gold standard test
      to diagnose food allergy or tolerance, biased samples in retrospective audits and
      lack of systematic protocols for triggering re-challenges. There is a need for
      population-based, prospective studies that use the gold standard oral food
      challenge (OFC) to diagnose food allergy at baseline and follow-up to develop SPT
      and sIgE thresholds that predict the course of food allergy.

PMID- 24132134
TI  - Psychological distress, related work attendance, and productivity loss in small
      to-medium enterprise owner/managers.
AB  - Owner/managers of small-to-medium enterprises (SMEs) are an under-researched
      population in terms of psychological distress and the associated health and
      economic consequences. Using baseline data from the evaluation of the Business in
      Mind program, a mental health promotion intervention amongst SME owner/managers,
      this study investigated: (i) prevalence of high/very high psychological distress,
      past-month sickness absenteeism and presenteeism days in SME owner/managers; (ii)
      associated, self-reported lost productivity; and (iii) associations between work,
      non-work and business-specific factors and work attendance behaviours. In our
      sample of 217 SME owner/managers 36.8% reported high/very high psychological
      distress. Of this group 38.7% reported past-month absenteeism, 82.5% reported
      past-month presenteeism, and those reporting presenteeism were 50% less
      productive as than usual. Negative binomial regression was used to demonstrate
      the independent effects of socio-demographic, work-related wellbeing and health
      related factors, as well as various individual and business characteristics on
      continuous measures of absenteeism and presenteeism days. Health-related factors
      (self-rated health and treatment) were the strongest correlates of higher
      presenteeism days (p < 0.05). Work-related wellbeing factors (job tension and job
      satisfaction) were the strongest correlates of higher absenteeism days (p <
      0.05). Higher educational attainment, treatment and neuroticism were also
      correlated with more absenteeism days. SME-specific information about the
      occurrence of psychological distress, work attendance behaviour, and the
      variables that influence these decisions, are needed for the development of
      guidelines for managing psychological distress within this sector. 

PMID- 24132135
TI  - Longitudinal influences of neighbourhood built and social environment on
      children's weight status.
AB  - The objective was to examine longitudinal 4-year-relationships between
      neighbourhood social environment and children's body mass index-standard
      deviation score (BMI-SDS) taking into account the built environment. Furthermore,
      we have analysed the influence of potential interactions between the social
      environment and family/social data on children's BMI-SDS. Between 2006-2008 and
      2010-2012, anthropometric measurements were conducted among 485 children (age at
      baseline: 6.1 (5.8-6.4)). Socio-demographic characteristics and perception of
      residential environment were reported by parents. Geographic Information Systems
      were used to examine street length, number of food outlets and distance to the
      nearest playground and park/green space within an 800 m Euclidian buffer of each
      participant address point. Additional data on neighbourhood characteristics
      (e.g., traffic density, walkability, crime rates) were obtained from the State
      Capital of Kiel, Germany. In a multivariate model, walkability, street type,
      socioeconomic status of the district and perceived frequency of passing
      trucks/buses were associated with BMI-SDS over 4 years, but only neighbourhood
      SES had an effect on change in BMI-SDS. However, familial/social factors rather
      than neighbourhood environment (especially social environment) had an impact on
      children's BMI-SDS over 4 years. Thus, social inequalities in childhood
      overweight are only partially explained by social neighbourhood environment.

PMID- 24132136
TI  - Circulating microRNAs as potential non-invasive biomarkers for the early
      detection of hypertension-related stroke.
AB  - Hypertension is one of the most important risk and modifiable factors for stroke.
      Crucial in managing the cerebrovascular damage caused by long-lasting and
      inadequately treated hypertension is not only lowering arterial blood pressure
      but also early predicting subtypes of hypertension-related stroke and applying
      more effective interventions. Accumulating evidence suggested that circulating
      microRNAs (miRNAs) could be developed as biomarkers for early recognition of the
      onset of a variety of diseases. The role of miRNAs has been extensively reviewed,
      involving cardiac hypertrophy, hypertensive heart failure, kidney failure and
      renal fibrosis. miRNA research in stroke is still in its infancy, although there
      are few literatures reviewing the role of miRNAs in the processes of hypertension
      related stroke. This review summarizes current advances in miRNAs regulation of
      critical pathogenic process underlying hypertension, ischemic stroke and
      hemorrhagic stroke, and highlights the potential of using circulating miRNAs as
      noninvasive biomarkers for the early detection of hypertension-related stroke. 

PMID- 24132137
TI  - Pulse pressure and subclinical peripheral artery disease.
AB  - Ankle-brachial index (ABI) measurement offers an easily available method to
      diagnose peripheral artery disease (PAD) and systemic atherosclerosis in early
      stage and thus to identify high-risk individuals for preventive interventions.
      The objective of this study was to assess the most practical criteria for the
      measurement of ABI in subjects with high cardiovascular risk. We examined 972
      asymptomatic, middle-aged high-risk subjects without manifested cardiovascular
      disease or previously diagnosed diabetes. The prevalence of PAD (defined as
      ABI?0.90) and borderline PAD (0.91-1.00) were 5% (95% confidence interval (CI) 4
      7%) (49/972) and 20% (95% CI 18-23%) (192/972), respectively. In multivariate
      analysis, female gender (odds ratio (OR) 0.71 (95% CI 0.53-0.97)), current
      smoking (OR 2.14 (95% CI 1.47-3.11)) and pulse pressure (OR 1.03 for each
      increase of 1 mm Hg (95% CI 1.01-1.04)) were associated with low ABI. Measuring
      ABI in subjects who smoke or have pulse pressure >65 mm Hg seems to be
      worthwhile. 

PMID- 24132138
TI  - Eight weeks of stretching training reduces aortic wave reflection magnitude and
      blood pressure in obese postmenopausal women.
AB  - The augmentation index (AIx, a marker of wave reflection) is reduced and
      peripheral artery vasodilation increased following acute stretching exercise. We
      examined the effects of stretching training (ST) on arterial function, blood
      pressure (BP) and sympathetic vasomotor modulation. Twenty-eight obese
      postmenopausal women (57+/-1 years) were randomized to a ST (n=14) or no-exercise
      control (CON) group ( n=14). ST included stretching exercises 3 days week(-1) for
      8 weeks. Brachial (b) and aortic (a) systolic BP (SBP), diastolic BP (DBP), mean
      arterial pressure (MAP), heart rate (HR), brachial-ankle pulse wave velocity
      (baPWV), carotid-femoral PWV (aPWV), femoral-ankle PWV (faPWV), AIx, low
      frequency component of SBP (LFSBP) and sit/reach score (SRS) were measured before
      and after interventions. There were significant decreases in bSBP (P<0.05), aSBP
      (P<0.01), aDBP (P<0.05), aMAP (P<0.01), aAIx (P<0.05) and LFSBP (P<0.05) after ST
      compared with CON. SRS significantly (P<0.01) increased after ST but not after
      CON. There were no significant effects (P>0.05) on HR, baPWV, aPWV and faPWV
      after ST or CON. Eight weeks of ST decreases BP, AIx and LFSBP in obese
      postmenopausal women. Our findings show that ST reduces peripheral and central
      BP, wave reflection magnitude and vascular sympathetic activity in obese
      postmenopausal women with prehypertension and hypertension. 

PMID- 24132139
TI  - Poor diagnostic performance of tilt testing in hypertensive patients with
      unexplained syncope.
AB  - Syncope is a common condition. Tilt testing with sublingual nitroglycerin (TT
      TNT) provides a test with good specificity and positivity rate in young and old
      patients. Its use in hypertensive patients with unexplained syncope has not been
      validated. The aims of this study were to evaluate the positivity rate,
      specificity and tolerability of TT-TNT in hypertensive patients with unexplained
      syncope. Five hundred and ten subjects (mean age 55 years) were enrolled, 388
      patients with unexplained syncope (73 hypertensive and 315 normotensive) and 122
      controls (59 hypertensive and 63 normotensive). All subjects underwent TT-TNT.
      The responses were classified as positive, negative or exaggerated (aspecific).
      In hypertensive patients, the usual hypotensive therapy was taken on the day of
      the test. In hypertensive controls, the positive responses were higher than in
      normotensives (19% vs 6%, P<0.001). The overall specificity was 81% in
      hypertensives and 94% in normotensives. The positivity rate was significantly
      lower in hypertensives (55% vs 72%, P<0.03). There was no significant difference
      between young patients and patients >65 years. TT was well tolerated, and no
      serious side effects occurred. TT potentiated with TNT has a lower positivity
      rate and specificity in hypertensive than in normotensive patients with syncope. 

PMID- 24132140
TI  - Clinical relevance of visit-to-visit blood pressure variability: impact on renal
      outcomes.
AB  - An impaired renal function has been found associated with very high
      cardiovascular (CV) risk, especially in subjects with type 2 diabetes.
      Microalbuminuria is a sensitive early marker of renal damage, often preceding the
      more advanced stages of diabetic nephropathy. Consistent evidence has been
      provided that any degree of quantifiable albuminuria, even in the range of
      normoalbuminuria, is a significant predictor of CV events and progression to end
      stage renal disease. This is of particular relevance in subjects with type 2
      diabetes in whom the prevalence of microalbuminuria may be as high as 50%. This
      has motivated the search for novel, yet modifiable risk factors the correction of
      which may contribute to prevention of albuminuria development and of renal
      impairment progression in patients with type 2 diabetes, aimed at further
      reducing the overall CV risk profile in these patients. One of these proposed
      novel risk factors is an increase in blood pressure variability (BPV). This
      suggestion is supported by a series of studies, carried out either in diabetic
      and in nondiabetic populations, which have provided evidence that an increased
      BPV, in addition to increased average BP levels, may be an independent predictor
      not only of CV events and mortality but also of development and progression of
      renal disease. The purpose of the present paper is to provide a critical review
      of the evidence exploring the relationship between BPV and renal dysfunction with
      particular emphasis on the relationship between visit-to-visit BPV and urinary
      albumin excretion variability. 

PMID- 24132142
TI  - A heterodimeric Fc-based bispecific antibody simultaneously targeting VEGFR-2 and
      Met exhibits potent antitumor activity.
AB  - Heterodimeric Fc designed by engineering the CH3 homodimeric interface of
      immunoglobulin G1 serves as an attractive scaffold for the generation of
      bispecific antibodies (bsAb) due to the favorable properties of the Fc region. In
      this study, we describe a heterodimeric Fc generated by substituting the
      conserved electrostatic interactions at the CH3 core interface with asymmetric
      hydrophobic interactions and introducing asymmetric, long-range electrostatic
      interactions at the rim of the CH3 interface. Coexpression of Fc proteins
      carrying the combined CH3 variant pairs in HEK293F cells produced the
      heterodimer, which was purified with more than 90% yield, and retained wild-type
      Fc biophysical properties. The heterodimeric Fc was exploited to generate a bsAb
      simultaneously targeting both the Met receptor tyrosine kinase and the VEGF
      receptor 2 (VEGFR-2), with two respective antigen-specific, single-chain variable
      fragments (scFv) into the N-terminus. The Met * VEGFR-2 bsAb bound concurrently
      to the two target antigens, efficiently inhibited the downstream signaling and
      tube formation stimulated by the two receptors in human endothelial cells, and
      exhibited more potent antitumor efficacy in MKN45 human gastric cancer xenograft
      models than both the parent monospecific antibody alone. Collectively, based on
      the newly designed heterodimeric Fc-based bsAb, our results provide the
      therapeutic potential of bsAb targeting both Met and VEGFR-2 simultaneously for
      the treatment of human cancers.

PMID- 24132144
TI  - Model-based exploration of the drivers of mountain cold-trapping in soil.
AB  - A pollutant is said to undergo mountain cold-trapping if it is found at higher
      concentrations in a surface medium (soil, snow, foliage) high on a mountain,
      where it is colder, than in the same medium lower on the mountain. The processes
      that lead to mountain cold-trapping in soil were explored for a set of
      hypothetical Perfectly Persistent Pollutants (PPPs) by varying several
      environmental parameters in a fugacity based fate and transport box model. These
      parameters were: the spatial scale of the mountain; the rate and location of
      rain; the amount of particles in the atmosphere; the presence and magnitude of
      the upslope temperature gradient. The relative potential of each hypothetical PPP
      to exhibit mountain cold-trapping was expressed in terms of its Mountaintop
      Contamination Potential (MCP). The PPPs with the highest MCPs were those that
      neither were deposited from the atmosphere to the surface in the lower zones in
      the model nor left the model domain without being deposited at all. The
      simulations revealed that under most conditions wet-gaseous deposition is the
      biggest driver of mountain cold-trapping in soils, and its effects are greatly
      enhanced by large negative temperature gradients and increased precipitation
      upslope. Dry-gaseous and wet-and-dry-particle deposition processes cause similar
      PPPs to exhibit mountain cold-trapping, and the contributions to MCP by the dry
      processes are of the same magnitude as wet-particle deposition. Dry gaseous
      deposition alone is insufficient to cause mountain cold-trapping in soils under
      any conditions modelled here. Those measuring organic contaminants in mountains
      should expect to find that mountains with different climates cold-trap different
      pollutants, and that some mountains may not exhibit upslope enrichment of any
      species. 

PMID- 24132143
TI  - ATP citrate lyase mediates resistance of colorectal cancer cells to SN38.
AB  - Combination chemotherapy is standard for metastatic colorectal cancer; however,
      nearly all patients develop drug resistance. Understanding the mechanisms that
      lead to resistance to individual chemotherapeutic agents may enable
      identification of novel targets and more effective therapy. Irinotecan is
      commonly used in first- and second-line therapy for patients with metastatic
      colorectal cancer, with the active metabolite being SN38. Emerging evidence
      suggests that altered metabolism in cancer cells is fundamentally involved in the
      development of drug resistance. Using Oncomine and unbiased proteomic profiling,
      we found that ATP citrate lyase (ACLy), the first-step rate-limiting enzyme for
      de novo lipogenesis, was upregulated in colorectal cancer compared with its
      levels in normal mucosa and in chemoresistant colorectal cancer cells compared
      with isogenic chemo-naive colorectal cancer cells. Overexpression of exogenous
      ACLy by lentivirus transduction in chemo-naive colorectal cancer cells led to
      significant chemoresistance to SN38 but not to 5-fluorouracil or oxaliplatin.
      Knockdown of ACLy by siRNA or inhibition of its activity by a small-molecule
      inhibitor sensitized chemo-naive colorectal cancer cells to SN38. Furthermore,
      ACLy was significantly increased in cancer cells that had acquired resistance to
      SN38. In contrast to chemo-naive cells, targeting ACLy alone was not effective in
      resensitizing resistant cells to SN38, due to a compensatory activation of the
      AKT pathway triggered by ACLy suppression. Combined inhibition of AKT signaling
      and ACLy successfully resensitized SN38-resistant cells to SN38. We conclude that
      targeting ACLy may improve the therapeutic effects of irinotecan and that
      simultaneous targeting of ACLy and AKT may be warranted to overcome SN38
      resistance.

PMID- 24132146
TI  - Bispidine as a helix inducing scaffold: examples of helically folded linear
      peptides.
AB  - We designed and synthesized bispidine-anchored peptides and showed that these
      peptides as small as (containing four chiral alpha-amino acid residues) adopt a
      right handed helical conformation. Bispidine anchored linear peptide adopts a
      helical conformation in solution and in the solid state. 

PMID- 24132147
TI  - Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin:
      possible mediation through the inhibition of NFkappaB signaling.
AB  - Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in
      arugula and has recently been reported to have anti-cancer properties in various
      cancer cells. In this study, we assessed the anti-inflammatory effects of erucin
      and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW
      264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse
      skin. In RAW 264.7 cells, erucin (2.5, 5 MUmol/L) inhibited LPS-induced
      production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced
      degradation of the inhibitor of kappaBalpha and translocation of p65 to the
      nucleus and, subsequently, reduced LPS-induced nuclear factor kappaB (NFkappaB)
      DNA binding activities, as well as the transcriptional activity of NFkappaB,
      leading to the decreased expression of NFkappaB-target genes, including tumor
      necrosis factor-alpha, interleukin (IL)-6, IL-1beta, inducible nitric oxide
      synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity
      of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly
      inhibited phorbol ester-induced formation of ear edema and expression of iNOS and
      COX-2 proteins. These results indicate that erucin exerts a potent anti
      inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines,
      which may be mediated, at least in part, via the inhibition of NFkappaB
      signaling. 

PMID- 24132148
TI  - Structural insights into a novel interkingdom signaling circuit by cartography of
      the ligand-binding sites of the homologous quorum sensing LuxR-family.
AB  - Recent studies have identified a novel interkingdom signaling circuit, via plant
      signaling molecules, and a bacterial sub-family of LuxR proteins, bridging
      eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are
      regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators
      that, although closely related to the quorum sensing (QS) LuxR family, do not
      bind or respond to canonical quorum sensing N-acyl homoserine lactones (AHLs),
      but only to specific host plant signal molecules. The large body of structural
      data available for several members of the QS LuxR family complexed with different
      classes of ligands (AHLs and other compounds), has been exploited to dissect the
      cartography of their regulatory domains through structure-based multiple sequence
      alignments, structural superimposition and a comparative analysis of the contact
      residues involved in ligand binding. In the absence of experimentally determined
      structures of members of the PAB LuxR solos subfamily, an homology model of its
      prototype OryR is presented, aiming to elucidate the architecture of its ligand
      binding site. The obtained model, in combination with the cartography of the
      regulatory domains of the homologous QS LuxRs, provides novel insights into the
      3D structure of its ligand-binding site and unveils the probable molecular
      determinants responsible for differences in selectivity towards specific host
      plant signal molecules, rather than to canonical QS compounds. 

PMID- 24132149
TI  - The epidermal growth factor receptor and its ligands in cardiovascular disease.
AB  - The epidermal growth factor receptor (EGFR) family and its ligands serve as a
      switchboard for the regulation of multiple cellular processes. While it is clear
      that EGFR activity is essential for normal cardiac development, its function in
      the vasculature and its role in cardiovascular disease are only beginning to be
      elucidated. In the blood vessel, endothelial cells and smooth muscle cells are
      both a source and a target of EGF-like ligands. Activation of EGFR has been
      implicated in blood pressure regulation, endothelial dysfunction, neointimal
      hyperplasia, atherogenesis, and cardiac remodeling. Furthermore, increased
      circulating EGF-like ligands may mediate accelerated vascular disease associated
      with chronic inflammation. Although EGFR inhibitors are currently being used
      clinically for the treatment of cancer, additional studies are necessary to
      determine whether abrogation of EGFR signaling is a potential strategy for the
      treatment of cardiovascular disease. 

PMID- 24132150
TI  - A comparative proteomic analysis of Pinellia ternata leaves exposed to heat
      stress.
AB  - Pinellia ternata is an important traditional Chinese medicinal plant. The growth
      of P. ternata is sensitive to high temperatures. To gain a better understanding
      of heat stress responses in P. ternata, we performed a comparative proteomic
      analysis. P. ternata seedlings were subjected to a temperature of 38  degrees C
      and samples were collected 24 h after treatment. Increased relative ion leakage
      and lipid peroxidation suggested that oxidative stress was frequently generated
      in rice leaves exposed to high temperature. Two-dimensional electrophoresis (2
      DE) was used to analyze heat-responsive proteins. More than 600 protein spots
      were reproducibly detected on each gel; of these spots, 20 were up-regulated, and
      7 were down-regulated. A total of 24 proteins and protein species were
      successfully identified by MALDI-TOF/TOF MS. These proteins and protein species
      were found to be primarily small heat shock proteins (58%) as well as proteins
      involved in RNA processing (17%), photosynthesis (13%), chlorophyll biosynthetic
      processes (4%), protein degradation (4%) and defense (4%). Using 2-DE Western
      blot analysis, we confirmed the identities of the cytosolic class II small heat
      shock protein (sHSPs-CII) identified by MS. The expression levels of four
      different proteins [cytosolic class I small heat shock protein (sHSPs-CI), sHSPs
      CII, mitochondrial small heat shock protein (sHSPs-MIT), glycine-rich RNA-binding
      protein (GRP)] were analyzed at the transcriptional level by quantitative real
      time PCR. The mRNA levels of three sHSPs correlated with the corresponding
      protein levels. However, GRP was down-regulated at the beginning of heat stress
      but then increased substantially to reach a peak after 24 h of heat stress. Our
      study provides valuable new insight into the responses of P. ternata to heat
      stress. 

PMID- 24132151
TI  - Mass spectrometry coupled experiments and protein structure modeling methods.
AB  - With the accumulation of next generation sequencing data, there is increasing
      interest in the study of intra-species difference in molecular biology,
      especially in relation to disease analysis. Furthermore, the dynamics of the
      protein is being identified as a critical factor in its function. Although
      accuracy of protein structure prediction methods is high, provided there are
      structural templates, most methods are still insensitive to amino-acid
      differences at critical points that may change the overall structure. Also,
      predicted structures are inherently static and do not provide information about
      structural change over time. It is challenging to address the sensitivity and the
      dynamics by computational structure predictions alone. However, with the fast
      development of diverse mass spectrometry coupled experiments, low-resolution but
      fast and sensitive structural information can be obtained. This information can
      then be integrated into the structure prediction process to further improve the
      sensitivity and address the dynamics of the protein structures. For this purpose,
      this article focuses on reviewing two aspects: the types of mass spectrometry
      coupled experiments and structural data that are obtainable through those
      experiments; and the structure prediction methods that can utilize these data as
      constraints. Also, short review of current efforts in integrating experimental
      data in the structural modeling is provided. 

PMID- 24132153
TI  - Thermal properties and crystallite morphology of nylon 66 modified with a novel
      biphenyl aromatic liquid crystalline epoxy resin.
AB  - In order to improve the thermal properties of important engineering plastics, a
      novel kind of liquid crystalline epoxy resin (LCER), 3,3',5,5' 
      Tetramethylbiphenyl-4,4' -diyl bis(4-(oxiran-2-ylmethoxy)benzoate) (M1) was
      introduced to blend with nylon 66 (M2) at high temperature. The effects of M1 on
      chemical modification and crystallite morphology of M2 were investigated by
      rheometry, thermo gravimetric analysis (TGA), dynamic differential scanning
      calorimetry (DSC) and polarized optical microscopy (POM). TGA results showed that
      the initial decomposition temperature of M2 increased by about 8  degrees C by
      adding 7% wt M1, indicating the improvement of thermal stability. DSC results
      illustrated that the melting point of composites decreased by 12  degrees C
      compared to M2 as the content of M1 increased, showing the improvement of
      processing property. POM measurements confirmed that dimension of nylon-66
      spherulites and crystallization region decreased because of the addition of
      liquid crystalline epoxy M1. 

PMID- 24132152
TI  - Absolute quantification of selected proteins in the human osteoarthritic
      secretome.
AB  - Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is
      driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome
      enables the global study of secreted proteins. These are an important class of
      molecules with roles in numerous pathological mechanisms. Although cartilage
      studies have identified profiles of secreted proteins, quantitative proteomics
      techniques have been implemented that would enable further biological questions
      to be addressed. To overcome this limitation, we used the secretome from human OA
      cartilage explants stimulated with IL-1beta and compared proteins released into
      the media using a label-free LC-MS/MS-based strategy. We employed QconCAT
      technology to quantify specific proteins using selected reaction monitoring. A
      total of 252 proteins were identified, nine were differentially expressed by IL-1
      beta stimulation. Selected protein candidates were quantified in absolute amounts
      using QconCAT. These findings confirmed a significant reduction in TIMP-1 in the
      secretome following IL-1beta stimulation. Label-free and QconCAT analysis
      produced equivocal results indicating no effect of cytokine stimulation on
      aggrecan, cartilage oligomeric matrix protein, fibromodulin, matrix
      metalloproteinases 1 and 3 or plasminogen release. This study enabled comparative
      protein profiling and absolute quantification of proteins involved in molecular
      pathways pertinent to understanding the pathogenesis of OA. 

PMID- 24132154
TI  - Molecular cloning and characterization of the calcineurin subunit A from Plutella
      xylostella.
AB  - Calcineurin (or PP2B) has been reported to be involved in an array of
      physiological process in insects, and the calcineurin subunit A (CNA) plays a
      central role in calcineurin activity. We cloned the CNA gene from Plutella
      xylostella (PxCNA). This gene contains an ORF of 1488 bp that encodes a 495 amino
      acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and
      humans respectively. The full-length of PxCNA and its catalytic domain (CNA(1
      341), defined as PxCNalpha) were both expressed in Escherichia coli. Purified
      recombinant PxCNA displayed no phosphatase activity, whereas recombinant
      PxCNalpha showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66
      S(-1) against pNPP. It could be activated at different degrees by Mn2+, Ni2+,
      Mg2+, and Ca2+. The optimum reaction pH was about 7.5 and the optimum reaction
      temperature was around 45  degrees C. An in vitro inhibition assay showed that
      okadaic acid (OA) and cantharidin (CTD) competitively inhibited recombinant
      PxCNalpha activity with the IC50 values of 8.95 MUM and 77.64 MUM, respectively.
      However, unlike previous reports, pyrethroid insecticides were unable to inhibit
      recombinant PxCNalpha, indicating that the P. xylostella calcineurin appears not
      to be sensitive to class II pyrethroid insecticides.

PMID- 24132156
TI  - Supramolecular interactions of terpyridine-derived cores of metallomesogen
      precursors.
AB  - Use of Hirshfeld surfaces calculated from crystal structure determinations on
      various transition metal ion complexes of three terpyridine ligands carrying
      trimethoxyphenyl substituents has enabled an assessment of the contribution made
      by the ligand components to the interactions determining the lattice structures,
      interactions expected also to be present in metallomesogens derived from similar
      ligands. The form of the link joining the trimethoxyphenyl substituent to the 4'
      position of 2,2';6',2''-terpyridine is of some importance. In the case of the
      Co(II) complexes of two of the ligands, their spin-crossover characteristics can
      be rationalised in terms of the different interactions seen in their lattices. 

PMID- 24132155
TI  - Multiple hits, including oxidative stress, as pathogenesis and treatment target
      in non-alcoholic steatohepatitis (NASH).
AB  - Multiple parallel hits, including genetic differences, insulin resistance and
      intestinal microbiota, account for the progression of non-alcoholic
      steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic
      reticulum (ER) and oxidative stress at the cellular level that subsequently
      induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress
      is considered a key contributor to progression from simple fatty liver to NASH.
      Although several clinical trials have shown that anti-oxidative therapy can
      effectively control hepatitis activities in the short term, the long-term effect
      remains obscure. Several trials of long-term anti-oxidant protocols aimed at
      treating cerebrovascular diseases or cancer development have failed to produce a
      benefit. This might be explained by the non-selective anti-oxidative properties
      of these drugs. Molecular hydrogen is an effective antioxidant that reduces only
      cytotoxic reactive oxygen species (ROS) and several diseases associated with
      oxidative stress are sensitive to hydrogen. The progress of NASH to
      hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus,
      targeting mitochondrial oxidative stress might be a good candidate for NASH
      treatment. Long term clinical intervention is needed to control this complex
      lifestyle-related disease. 

PMID- 24132159
TI  - Investigation on the mechanism of water-assisted palladium-catalyzed benzylic C-H
      amination by N-fluorobenzenesulfonimide.
AB  - A combination of computational and experimental methods was carried out to
      elucidate the mechanism of palladium-catalyzed water-assisted benzylic C-H
      amination with N-fluorobenzenesulfonimide (NFSI), which involved the oxidative
      addition of Pd(II) to Pd(IV)-species as a rate-limiting step, followed by water
      assisted concerted metalation-deprotonation (CMD) of the Pd(IV) complex and water
      assisted reductive elimination (RE) processes, and then a nucleophilic addition
      process to generate the final product and complete the catalytic cycle. The
      stability of the Pd(IV) complex could be ascribed to the suitable ligands with
      strong sigma-donors and resistance to decomposition, as well as being
      sufficiently bulky because the water-clusters assembled the ligands through
      hydrogen bonds to act as one multidentate ligand. Calculation results suggested
      that water also plays a crucial role as a proton transferring bridge in water
      assisted CMD and RE processes. The corresponding experimental findings
      substantiate the expectation. Additionally, NFSI was found to act as both the
      oxidant and the nitrogen source to facilitate the reaction, while the steric
      effect of the bulky -N(SO2Ph)2 group contributed to circumventing the o-C-H
      amination. In this reaction, we investigated a novel spiro-cyclopalladation
      intermediate, formed by the reaction of the Pd(IV) centre with pristine-carbon
      instead of ortho-carbon, which might be valuable for our understanding and
      further development of transition metal catalyzed C-H functionalization. 

PMID- 24132157
TI  - Molecular cloning, sequence characterization and expression analysis of a CD63
      homologue from the coleopteran beetle, Tenebrio molitor.
AB  - CD63, a member of the tetraspanin membrane protein family, plays a pivotal role
      in cell growth, motility, signal transduction, host-pathogen interactions and
      cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from
      larvae of a coleopteran beetle, Tenebrio molitor. The cDNA is comprised of an
      open reading frame of 705 bp, encoding putative protein of 235 amino acid
      residues. In silico analysis shows that the protein has four putative
      transmembrane domains and one large extracellular loop. The characteristic "Cys
      Cys-Gly" motif and "Cys188" residues are highly conserved in the large
      extracellular loop. Phylogenetic analysis of TmCD63 revealed that they belong to
      the insect cluster with 50%-56% identity. Analysis of spatial expression patterns
      demonstrated that TmCD63 mRNA is mainly expressed in gut and Malphigian tubules
      of larvae and the testis of the adult. Developmental expression patterns of CD63
      mRNA showed that TmCD63 transcripts are detected in late larval, pupal and adult
      stages. Interestingly, TmCD63 transcripts are upregulated to the maximum level of
      4.5 fold, in response to DAP-type peptidoglycan during the first 6 h, although
      other immune elicitors also caused significant increase to the transcript level
      at later time-points. These results suggest that CD63 might contribute to T.
      molitor immune response against various microbial pathogens. 

PMID- 24132160
TI  - Roles of T cell-associated L-selectin and beta7 integrins during induction and
      regulation of chronic colitis.
AB  - BACKGROUND: L-selectin (CD62L) and beta(7) integrins are important for
      trafficking of naive T cells under steady-state conditions. The objectives of
      this study were to dissect the requirements for T cell-associated CD62L and
      beta(7) integrins during initiation, progression, and regulation of chronic
      colitis. METHODS: Using the T-cell transfer model, we compared colitogenic
      potential between T cells lacking one or both of these molecules with wild-type T
      cells. To assess trafficking of cells to the secondary lymphoid tissue and the
      gut, we performed co-homing experiments. RESULTS: Adoptive transfer of wild-type,
      CD62L(-/-) or beta(7)(-/-) single-deficient T cells induced moderate to severe
      disease with slightly different kinetics. However, transfer of CD62L(-/-)
      beta(7)(-/-) double-deficient (DKO) T cells produced significantly attenuated gut
      inflammation, which correlated with fewer T cells and reduced levels of
      proinflammatory cytokines in the colon lamina propria. Our subsequent experiments
      established that lack of colitogenic potential of these cells was due to
      inability of DKO T cells to home to the secondary lymphoid tissue. Furthermore,
      homing of in vitro-generated effector DKO T cells to the inflamed intestine was
      significantly impaired. Lastly, DKO regulatory T cells were ineffective at
      suppressing colitis induced by wild-type T cells. CONCLUSIONS: We established
      that T cells can use either CD62L(-/-) or beta(7)(-/-) integrins to induce
      chronic colitis, but lack of both abrogates their colitogenic potential. Effector
      T cells critically rely on beta(7) integrin during their recruitment to the
      inflamed intestinal mucosa. Finally, regulation of intestinal inflammation by
      regulatory T cells requires one or both of these adhesion molecules.

PMID- 24132161
TI  - Mucosal healing is associated with improved long-term outcome of maintenance
      therapy with natalizumab in Crohn's disease.
AB  - BACKGROUND: Natalizumab is an efficacious agent for induction and maintenance of
      remission in patients with Crohn's disease (CD) who have failed anti-tumor
      necrosis factor agents. We aimed to assess the impact of endoscopic severity and
      mucosal healing on the long-term outcome of natalizumab treatment in CD. METHODS:
      We retrospectively assessed endoscopic severity according to the Simple
      Endoscopic Score for Crohn's Disease in patients with CD who received natalizumab
      therapy. The degree of endoscopic severity before natalizumab treatment and
      mucosal healing after treatment and their correlation with long-term outcome were
      studied. RESULTS: Thirty-two patients with CD (15 male, median age 32.5 years)
      receiving natalizumab underwent at least 1 colonoscopy before or during
      natalizumab treatment. All patients had previously failed immunomodulator(s), and
      31 failed anti-tumor necrosis factor agent(s). Mean duration of natalizumab
      treatment was 14.1 months. Baseline Simple Endoscopic Score for CD was
      categorized into quartiles, and those with a greater score were less likely to
      respond to treatment as assessed by Kaplan-Meier survival analysis (n = 32, log
      rank test, P = 0.0055). Mucosal healing (decrease of Simple Endoscopic Score for
      CD of >70%) was achieved in 11 of 26 patients (42.3%), and this was correlated
      with an improved long-term outcome (log-rank test, P = 0.0063). CONCLUSIONS: The
      degree of endoscopic inflammation correlates to response to natalizumab and
      maintenance of remission. These findings provide prognostic information for
      patient management decisions.

PMID- 24132162
TI  - Automation of 3D cell culture using chemically defined hydrogels.
AB  - Drug development relies on high-throughput screening involving cell-based assays.
      Most of the assays are still based on cells grown in monolayer rather than in
      three-dimensional (3D) formats, although cells behave more in vivo-like in 3D. To
      exemplify the adoption of 3D techniques in drug development, this project
      investigated the automation of a hydrogel-based 3D cell culture system using a
      liquid-handling robot. The hydrogel technology used offers high flexibility of
      gel design due to a modular composition of a polymer network and bioactive
      components. The cell inert degradation of the gel at the end of the culture
      period guaranteed the harmless isolation of live cells for further downstream
      processing. Human colon carcinoma cells HCT-116 were encapsulated and grown in
      these dextran-based hydrogels, thereby forming 3D multicellular spheroids.
      Viability and DNA content of the cells were shown to be similar in automated and
      manually produced hydrogels. Furthermore, cell treatment with toxic Taxol
      concentrations (100 nM) had the same effect on HCT-116 cell viability in manually
      and automated hydrogel preparations. Finally, a fully automated dose-response
      curve with the reference compound Taxol showed the potential of this hydrogel
      based 3D cell culture system in advanced drug development. 

PMID- 24132163
TI  - Application of ggplot2 to Pharmacometric Graphics.
AB  - Visualization is a powerful mechanism for extracting information from data.
      ggplot2 is a contributed visualization package in the R programming language,
      which creates publication-quality statistical graphics in an efficient, elegant,
      and systematic manner. This article summarizes key features of the package with
      examples from pharmacometrics and pointers to available resources for learning
      ggplot2.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e79;
      doi:10.1038/psp.2013.56; advance online publication 16 October 2013. 

PMID- 24132164
TI  - Application of physiologically based pharmacokinetic modeling to predict
      acetaminophen metabolism and pharmacokinetics in children.
AB  - Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that
      undergoes extensive phase I and II metabolism. To better understand the kinetics
      of this process and to characterize the dynamic changes in metabolism and
      pharmacokinetics (PK) between children and adults, we developed a physiologically
      based PK (PBPK) model for APAP integrating in silico, in vitro, and in vivo PK
      data into a single model. The model was developed and qualified for adults and
      subsequently expanded for application in children by accounting for maturational
      changes from birth. Once developed and qualified, it was able to predict clinical
      PK data in neonates (0-28 days), infants (29 days to <2 years), children (2 to
      <12 years), and adolescents (12-17 years) following intravenous and orally
      administered APAP. This approach represents a general strategy for projecting
      drug exposure in children, in the absence of pediatric PK information, using
      previous drug- and system-specific information of adults and children through
      PBPK modeling.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e80;
      doi:10.1038/psp.2013.55; advance online publication 16 October 2013. 

PMID- 24132165
TI  - Evaluating the environmental fate of short-chain chlorinated paraffins (SCCPs) in
      the Nordic environment using a dynamic multimedia model.
AB  - Short chain chlorinated paraffins (SCCPs) raise concerns due to their potential
      for persistence, bioaccumulation, long-range transport and adverse effects. An
      understanding of their environmental fate remains limited, partly due to the
      complexity of the mixture. The purpose of this study was to evaluate whether a
      mechanistic, integrated, dynamic environmental fate and bioaccumulation
      multimedia model (CoZMoMAN) can reconcile what is known about environmental
      emissions and human exposure of SCCPs in the Nordic environment. Realistic SCCP
      emission scenarios, resolved by formula group, were estimated and used to predict
      the composition and concentrations of SCCPs in the environment and the human food
      chain. Emissions at the upper end of the estimated range resulted in predicted
      total concentrations that were often within a factor of 6 of observations.
      Similar model performance for a complex group of organic contaminants as for the
      well-known polychlorinated biphenyls strengthens the confidence in the CoZMoMAN
      model and implies a relatively good mechanistic understanding of the
      environmental fate of SCCPs. However, the degree of chlorination predicted for
      SCCPs in sediments, fish, and humans was higher than observed and poorly
      established environmental half-lives and biotransformation rate constants
      contributed to the uncertainties in the predicted composition and ?SCCP
      concentrations. Improving prediction of the SCCP composition will also require
      better constrained estimates of the composition of SCCP emissions. There is,
      however, also large uncertainty and lack of coherence in the existing
      observations, and better model-measurement agreement will require improved
      analytical methods and more strategic sampling. More measurements of SCCP levels
      and compositions in samples from background regions are particularly important. 

PMID- 24132166
TI  - Promise of human induced pluripotent stem cells in skin regeneration and
      investigation.
AB  - Induced pluripotent stem cell (iPSC) technology has initiated a new era in
      biomedical science. The skin has been realized as an ideal platform for iPSC
      applications; unlike other organs, the skin is easily accessible, highly
      proliferative, and reconstitutable. Currently, skin equivalents can be generated
      from iPSCs not only from healthy individuals but also from patients with
      genodermatoses, providing novel platforms for dissecting disease pathophysiology
      and establishing cell-based therapy. With their developmental plasticity, iPSCs
      may also enable the regeneration of skin appendages. The iPSC technology may
      provide novel remedies for intractable disorders, once key issues particularly,
      safety concerns, are cleared. 

PMID- 24132170
TI  - Efficient cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.
AB  - Nitrogen heterocycles could be prepared in good yields via intramolecular
      cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF. 

PMID- 24132176
TI  - Pulse-reverse electrodeposition of transparent nickel phosphide film with porous
      nanospheres as a cost-effective counter electrode for dye-sensitized solar cells.
AB  - A Ni2P nanolayer with porous nanospheres was directly coated on fluorine-doped
      tin oxide glass by pulse-reverse deposition as a low-cost counter electrode
      catalyst for dye-sensitized solar cells, and the photoelectron conversion
      efficiency of the cell was increased to 7.32% by using a porous nanosphere
      catalyst due to the significantly improved ion transport. 

PMID- 24132177
TI  - Radiation-modified natural zeolites for cleaning liquid nuclear waste
      (irradiation against radioactivity).
AB  - There have been comparatively few investigations reported of radiation effects in
      zeolites, although it is known that these materials may be modified substantially
      by exposure to ionizing radiation. Thus, by exposure to gamma-rays or high-energy
      particles, the charge states of atoms may be changed so to create, and
      accumulate, lattice point defects, and to form structurally disordered regions.
      Such a technique may permit the creation, in a controlled fashion, of
      additionally useful properties of the material while preserving its essential
      stoichiometry and structure. Accordingly, we present an application, in which the
      cation-exchange capacity of a natural zeolite (clinoptilolite) is substantially
      enhanced, for the treatment/decontamination of water contaminated with
      radionuclides e.g. (134)Cs, (137)Cs and (90)Sr, by its exposure to high-energy (8
      MeV) electrons, and to different total doses.

PMID- 24132178
TI  - New spirotetronate antibiotics, lobophorins H and I, from a South China Sea
      derived Streptomyces sp. 12A35.
AB  - Strain 12A35 was isolated from a deep-sea sediment collected from the South China
      Sea and showed promising antibacterial activities. It was identified as
      Streptomyces sp. by the 16S rDNA sequence analysis. Bioassay-guided fractionation
      using HP20 adsorption, flash chromatography over silica gel and octadecylsilyl
      (ODS) and semi-preparative HPLC, led to the isolation and purification of five
      metabolites from the fermentation culture of 12A35. Two new spirotetronate
      antibiotics, lobophorins H (1) and I (2), along with three known analogues, O
      beta-kijanosyl-(1->17)-kijanolide (3), lobophorins B (4) and F (5) were
      characterized by 1D, 2D-NMR and MS data. These compounds exhibited significant
      inhibitory activities against Bacillus subtilis. Compounds 1 and 5 exhibited
      moderate activities against Staphylococcus aureus. In particular, the new
      compound lobophorin H (1) showed similar antibacterial activities against B.
      subtilis CMCC63501 to ampicillin. 

PMID- 24132181
TI  - A novel strategy for the construction of substituted benzoxazoles via a tandem
      oxidative process.
AB  - A practical and simple synthesis of benzoxazoles from easily available substrates
      was developed. The protocol is triggered by an iron-catalyzed tandem oxidative
      process from simple toluene derivatives and 2-aminophenols. This method
      represents a straightforward approach to access substituted benzoxazoles. 

PMID- 24132179
TI  - Enhanced anti-obesity activities of red mold dioscorea when fermented using deep
      ocean water as the culture water.
AB  - Deep ocean water (DOW) has, in previous studies, been found to be a novel anti
      obesity drink and useful in raising Monascus-produced monascin and ankaflavin
      levels. This may resolve the limited anti-obesity ability of red mold dioscorea
      (RMD) known as the Monascus purpureus-fermented Disocorea batatas. This study
      aims to compare the anti-obesity effect of DOW-cultured RMD (DOW-RMD) and ultra
      pure water-cultured RMD (UPW-RMD) in rats fed on a high fat diet. Moreover, the
      effect of ions composition of DOW and DOW-influenced functional metabolites
      change of RMD on the differentiation and lipogenesis regulation were investigated
      using 3T3-L1 pre-adipocytes. In the animal test, compared to UPW-RMD, DOW-RMD
      possessed better ability to inhibit increases in weight gain, and better feed
      efficiency, body-fat pad and cross-sectional area of adipocytes. In the cell
      test, the anti-obesity abilities of DOW-RMD in inhibiting PPARgamma and
      C/EBPalpha expression in differentiation and lipoprotein lipase activity in
      lipogenesis were contributed to by the DOW-increased monascin and ankaflavin
      levels and the ions of DOW, respectively. 

PMID- 24132182
TI  - Three-dimensional fibroblast morphology on compliant substrates of controlled
      negative curvature.
AB  - Traditionally, cell biological investigations have mostly employed cells growing
      on flat, two-dimensional, hard substrates, which are of questionable utility in
      mimicking microenvironments in vivo. We engineered a novel scaffold to achieve
      cell culture in the third dimension (3D), where fibroblasts lose the strong
      dorsal-ventral asymmetry in the distribution of cytoskeletal and adhesion
      components that is induced by growth on flat substrates. The design principle of
      our new 3D substrate was inspired by recent advances in engineering cellular
      microenvironments in which rigidity and the patterning of adhesion ligands were
      tuned on two-dimensional substrates; the engineered substrates enable independent
      control over biochemical and mechanical factors to elucidate how mechanical cues
      affect cellular behaviours. The 3D substrates consisted of polyacrylamide
      scaffolds of highly ordered, uniform pores coated with extracellular matrix
      proteins. We characterized important parameters for fabrication and the
      mechanical properties of polyacrylamide scaffolds. We then grew individual
      fibroblasts in the identical pores of the polyacrylamide scaffolds, examining
      cellular morphological, actin cytoskeletal, and adhesion properties. We found
      that fibroblasts sense the local rigidity of the scaffold, and exhibit a 3D
      distribution of actin cytoskeleton and adhesions that became more pronounced as
      the pore size was reduced. In small pores, we observed that elongated adhesions
      can exist without attachment to any solid support. Taken together, our results
      show that the use of negatively curved surfaces is a simple method to induce cell
      adhesions in 3D, opening up new degrees of freedom to explore cellular
      behaviours. 

PMID- 24132183
TI  - Maternal exposure to dioxin imprints sexual immaturity of the pups through fixing
      the status of the reduced expression of hypothalamic gonadotropin-releasing
      hormone.
AB  - Our previous studies have shown that treatment of pregnant rats with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD; 1 MUg/kg) at gestational day (GD) 15 reduces
      the pituitary synthesis of luteinizing hormone (LH) during the late fetal and
      early postnatal period, leading to the imprinting of defects in sexual behaviors
      at adulthood. However, it remains unclear how the attenuation of pituitary LH is
      linked to sexual immaturity. To address this issue, we performed a DNA microarray
      analysis to identify the gene(s) responsible for dioxin-induced sexual immaturity
      on the pituitary and hypothalamus of male pups, born of TCDD-treated dams, at the
      age of postnatal day (PND) 70. Among the reduced genes, we focused on
      gonadotropin-releasing hormone (GnRH) in the hypothalamus because of published
      evidence that it has a role in sexual behaviors. An attenuation by TCDD of GnRH
      expression emerged at PND4, and no subsequent return to the control level was
      seen. A change in neither DNA methylation nor histone acetylation accounted for
      the reduced expression of GnRH. Intracerebroventricular infusion of GnRH to the
      TCDD-exposed pups after reaching maturity restored the impairment of sexual
      behaviors. Supplying equine chorionic gonadotropin, an LH-mimicking hormone, to
      the TCDD-exposed fetuses at GD15 resulted in a recovery from the reduced
      expression of GnRH, as well as from the defects in sexual behavior. These results
      strongly suggest that maternal exposure to TCDD fixes the status of the lowered
      expression of GnRH in the offspring by reducing the LH-assisted steroidogenesis
      at the perinatal stage, and this mechanism imprints defects in sexual behaviors
      at adulthood. 

PMID- 24132184
TI  - The right to health is coming of age: evidence of impact and the importance of
      leadership.

PMID- 24132185
TI  - Protein destabilisation in ionic liquids: the role of preferential interactions
      in denaturation.
AB  - The preferential binding of anions and cations in aqueous solutions of the ionic
      liquids (ILs) 1-butyl-3-methylimidazolium ([C4mim](+)) and 1-ethyl-3
      methylimidazolium ([C2mim](+)) chloride and dicyanamide (dca(-)) with the small
      alpha-helical protein Im7 was investigated using a combination of differential
      scanning calorimetry, NMR spectroscopy and molecular dynamics (MD) simulations.
      Our results show that direct ion interactions are crucial to understand the
      effects of ILs on the stability of proteins and that an anion effect is dominant.
      We show that the binding of weakly hydrated anions to positively charged or polar
      residues leads to the partial dehydration of the backbone groups, and is critical
      to control stability, explaining why dca(-) is more denaturing than Cl(-). Direct
      cation-protein interactions also mediate stability; cation size and
      hydrophobicity are relevant to account for destabilisation as shown by the effect
      of [C4mim](+) compared to [C2mim](+). The specificity in the interaction of IL
      ions with protein residues established by weak favourable interactions is
      confirmed by NMR chemical shift perturbation, amide hydrogen exchange data and MD
      simulations. Differences in specificity are due to the balance of interaction
      established between ion pairs and ion-solvent that determine the type of residues
      affected. When the interaction of both cation and anion with the protein is
      strong the net result is similar to a non-specific interaction, leading
      ultimately to unfolding. Since the nature of the ions is a determinant of the
      level of interaction with the protein towards denaturation or stabilisation, ILs
      offer a unique possibility to modulate protein stabilisation or even folding
      events. 

PMID- 24132186
TI  - Temperature, light and solvent-induced spin transition in a 3D 2-fold
      interpenetrated PtS-type porous coordination polymer.
AB  - A 3D 2-fold interpenetrated porous coordination polymer,
      [Fe(NCS)2(tppm)].5CH3OH.2CH2Cl2 (.sol, tppm = 4,4',4'',4'''-tetrakis(4
      pyridylethen-2-yl)tetraphenylmethane), was synthesized, which showed temperature,
      light and solvent-induced spin-crossover behaviours. 

PMID- 24132187
TI  - Coronary evaginations are associated with positive vessel remodelling and are
      nearly absent following implantation of newer-generation drug-eluting stents: an
      optical coherence tomography and intravascular ultrasound study.
AB  - OBJECTIVES: The purpose of this study was to assess the occurrence, predictors,
      and mechanisms of optical coherence tomography (OCT)-detected coronary
      evaginations following drug-eluting stent (DES) implantation. BACKGROUND:
      Angiographic ectasias and aneurysms in stented segments have been associated with
      a risk of late stent thrombosis. Using OCT, some stented segments show coronary
      evaginations reminiscent of ectasias. METHODS: Evaginations were defined as
      outward bulges in the luminal contour between struts. They were considered major
      evaginations (MEs) when extending >=3 mm along the vessel length, with a depth
      >=10% of the stent diameter. A total of 228 patients who had sirolimus (SES)-,
      paclitaxel-, biolimus-, everolimus (EES)-, or zotarolimus (ZES)-eluting stents
      implanted in 254 lesions, were analysed after 1, 2, or 5 years; and serial
      assessment using OCT and intravascular ultrasound (IVUS) was performed post
      intervention and after 1 year in 42 patients. RESULTS: Major evaginations
      occurred frequently at all time points in SES (~26%) and were rarely seen in EES
      (3%) and ZES (2%, P = 0.003). Sirolimus-eluting stent implantation was the
      strongest independent predictor of ME [adjusted OR (95% CI) 9.1 (1.1-77.4), P =
      0.008]. Malapposed and uncovered struts were more common in lesions with vs.
      without ME (77 vs. 25%, P < 0.001 and 95 vs. 20%, P < 0.001, respectively) as was
      thrombus [49 vs. 14%, OR 7.3 (95% CI: 1.7-31.2), P = 0.007]. Post-intervention
      intra-stent dissection and protrusion of the vessel wall into the lumen were
      associated with an increased risk of evagination at follow-up [OR (95% CI): 2.9
      (1.8-4.9), P < 0.001 and 3.3 (1.6-6.9), P = 0.001, respectively]. In paired IVUS
      analyses, lesions with ME showed a larger increase in the external elastic
      membrane area (20% area change) compared with lesions without ME (5% area change,
      P < 0.001). CONCLUSION: Optical coherence tomography-detected MEs are a specific
      morphological footprint of early-generation SES and are nearly absent in newer
      generation ZES and EES. Evaginations appear to be related to vessel injury at
      baseline; are associated with positive vessel remodelling; and correlate with
      uncoverage, malapposition, and thrombus at follow-up.

PMID- 24132188
TI  - Atypical hypertrophic cardiomyopathy of the left lateral wall leading to
      ventricular tachycardia.

PMID- 24132189
TI  - Can speckle-tracking imaging improve the reliability of echocardiographic
      parameters for outcome evaluation in clinical trials?

PMID- 24132191
TI  - An interview study of young adults born to mothers with mild intellectual
      disability.
AB  - A group of 10 young adults from a population-based series in Sweden, of
      originally 42 individuals, born to mothers with mild intellectual disability
      (ID), were interviewed with regard to their experiences during childhood,
      adolescence, and their current situation. The interview revealed that 6 of the 10
      individuals had been removed from their biological parents during childhood, 6
      reported clear child abuse and/or neglect, and 6 individuals had mild ID. The
      majority of the individuals reported difficulties in their relations with family
      and in school. The small number of participants (n = 10) who could be personally
      interviewed reflected the major problems that were encountered in the process of
      making contact with this group of young individuals. In conclusion, this study
      adds to other reports that children of mothers with ID constitute an extremely
      vulnerable group. Therefore, these families need full and continuous attention
      from the supportive systems in society. 

PMID- 24132190
TI  - Ischaemic cardiac outcomes in patients with atrial fibrillation treated with
      vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial.
AB  - AIMS: We investigated the prevalence of prior myocardial infarction (MI) and
      incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF)
      patients. METHODS AND RESULTS: In ROCKET AF, 14 264 patients with nonvalvular AF
      were randomized to rivaroxaban or warfarin. The key efficacy outcome for these
      analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis
      was performed on patients while on treatment. Rates are per 100 patient-years.
      Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients
      without prior MI, these patients were more likely to be male (75 vs. 57%), on
      aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs.
      59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score
      (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs.
      54%). CV death, MI, or UA rates tended to be lower in patients assigned
      rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95%
      confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were
      higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04,
      95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban
      compared with warfarin in prior MI compared with no prior MI (P interaction =
      0.10). CONCLUSION: Prior MI was common and associated with substantial risk for
      subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared
      with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

PMID- 24132192
TI  - Implementation of the care programme approach across health and social services
      for dual diagnosis clients.
AB  - BACKGROUND: Care for clients with mental health problems and concurrent
      intellectual disability (dual diagnosis) is currently expected to be provided
      through the care programme approach (CPA), an approach to provide care to people
      with mental health problems in secondary mental health services. When CPA was
      originally introduced into UK mental health services in the 1990s, its
      implementation was slow and problematic, being hampered in part by problems
      occurring at a strategic level as health and social service organizations
      attempted to integrate complex systems. This article reports on a study of a more
      recent attempt to implement CPA for dual diagnosis clients in one mental health
      foundation trust, aiming to gauge progress and identify factors at the strategic
      level that were helping or hindering progress this time round. METHODS: The study
      took place in a mental health National Health Service (NHS) Foundation Trust in a
      large English city, which was implementing a joint mental health and intellectual
      disability CPA policy across five of its constituent boroughs. Semi-structured
      interviews with key informants at Trust and borough levels focused on the Trust's
      overall strategy for implementing CPA and on how it was being put into practice
      at the front line. Documentary analysis and the administration of the Partnership
      Assessment Tool were also undertaken. Data were analysed using a framework
      approach. RESULTS: Progress in implementing CPA varied but overall was extremely
      limited in all the boroughs. The study identified six key contextual challenges
      that significantly hindered the implementation progress. These included
      organizational complexity; arrangements for governance and accountability;
      competing priorities; financial constraints; high staff turnover and complex
      information and IT systems. The only element of policy linked to CPA that had
      been widely taken up was the Greenlight Framework and Audit Toolkit (GLTK). The
      fact that the toolkit had targets and penalties associated with its
      implementation appeared to have given it priority. CONCLUSION: None of the
      contextual challenges identified in this study were specifically related to CPA
      as a policy or to the needs and circumstances of dual diagnosis clients.
      Nevertheless, they inhibited the types of organizational change and partnership
      working that implementing CPA for a client group of this kind required. Unless
      these more generic factors are acknowledged and addressed when introducing
      policies such as CPA, the chances of effective implementation will inevitably be
      compromised.

PMID- 24132194
TI  - Atomic scale investigation of a graphene nano-ribbon based high efficiency spin
      valve.
AB  - Graphene nanoribbons based electronic devices present many interesting physical
      properties. We designed and investigated the spin-dependent electron transport of
      a device configuration, which is easy to be fabricated, with an oxygen-terminated
      ZGNR central scatter region between two hydrogen-terminated ZGNR electrodes.
      According to the analysis based on non-equilibrium Green's function and density
      functional theory, the proposed device could maintain its good spin-filter
      performance (80% to 99%) and have a stable magneto resistance value up to 10(5)%.
      The spin dependent electron transmission spectrum and space-resolve density of
      states are employed to investigate the physical origin of the spin-polarized
      current and magneto resistance. 

PMID- 24132195
TI  - Heteroaryl chalcones: design, synthesis, X-ray crystal structures and biological
      evaluation.
AB  - Chalcone derivatives have attracted increasing attention due to their numerous
      pharmacological activities. Changes in their structures have displayed high
      degree of diversity that has proven to result in a broad spectrum of biological
      activities. The present study highlights the synthesis of some halogen
      substituted chalcones 3(a-i) containing the 5-chlorothiophene moiety, their X-ray
      crystal structures and the evaluation of possible biological activities such as
      antibacterial, antifungal and reducing power abilities. The results indicate the
      tested compounds show a varied range of inhibition values against all the tested
      microbial strains. Compound 3c with a p-fluoro substituent on the phenyl ring
      exhibits elevated antimicrobial activity, whereas the compounds 3e and 3f
      displayed the least antimicrobial activities. The compounds 3d, 3e, 3f and 3i
      showed good ferric and cupric reducing abilities, and the compounds 3b and 3c
      showed the weakest reducing power in the series. 

PMID- 24132196
TI  - Microwave assisted synthesis, antifungal activity and DFT theoretical study of
      some novel 1,2,4-triazole derivatives containing the 1,2,3-thiadiazole moiety.
AB  - In order to investigate the biological activity of 1,2,4-triazole compounds,
      seventeen novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole moieties
      were synthesized by multi-step reactions under microwave assisted conditions. The
      structures were characterized by 1H-NMR, 13C-NMR, MS and elemental analyses. The
      target compounds were evaluated for their in vivo fungicidal activities against
      Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, and
      Pseudoperonospora cubensis, and the results indicated that some of the title
      compounds displayed good fungicidal activities. Theoretical calculations on the
      title compounds were carried out at the B3LYP/6-31G (d,p). level. The full
      geometry optimization was carried out using the 6-31G(d,p) basis set, and the
      frontier orbital energy, atomic net charges were discussed, and the structure
      activity relationships were also studied. 

PMID- 24132197
TI  - An efficient and facile methodology for bromination of pyrimidine and purine
      nucleosides with sodium monobromoisocyanurate (SMBI).
AB  - An efficient and facile strategy has been developed for bromination of
      nucleosides using sodium monobromoisocyanurate (SMBI). Our methodology
      demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C
      8 position of purine nucleosides. Unprotected and also several protected
      nucleosides were brominated in moderate to high yields following this procedure. 

PMID- 24132198
TI  - The effect of molecular crowding on the stability of human c-MYC promoter
      sequence I-motif at neutral pH.
AB  - We have previously shown that c-MYC promoter sequences can form stable i-motifs
      in acidic solution (pH 4.5-5.5). In terms of drug targeting, the question is
      whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH.
      In this work, we have investigated the stability of a mutant c-MYC i-motif in
      solutions containing a molecular crowding agent. The crowded nuclear environment
      was modeled by the addition of up to 40% w/w polyethylene glycols having
      molecular weights up to 12,000 g/mol. CD and DSC were used to establish the
      presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4
      to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH
      values as high as 6.7 in crowded solutions. Generic dielectric constant effects,
      e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or
      the formation of non-specific PEG/DNA complexes appear to contribute
      insignificantly to i-motif stabilization. Molecular crowding, largely an excluded
      volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol,
      appears to be responsible for stabilizing the more compact i-motif over the
      random coil at higher pH values. 

PMID- 24132199
TI  - Ring-opening polymerization of L-lactic acid O-carboxyanhydrides initiated by
      alkoxy rare earth compounds.
AB  - The ring-opening polymerization of L-lactic acid O-carboxyanhydrides was
      initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high
      yields and relatively high molecular weight PLAs were obtained within 4 h at 25 
      degrees C. The reaction was highly controllable and easy to conduct, and the
      molecular weight distribution of the PLAs was rather narrow (Mw/Mn = 1.10-1.36).
      NMR analysis showed that one end of the PLA chain consisted of an isopropoxy
      group, while the other end of the chain contained a hydroxyl group. Due to their
      availability and high polymerizability, Lac-OCAs are promising monomers for the
      preparation of tailored architectures derived from well-defined PLAs.

PMID- 24132200
TI  - Intimal hyperplasia following implantation of helical-centreline and straight
      centreline stents in common carotid arteries in healthy pigs: influence of
      intraluminal flow.
AB  - Intimal hyperplasia (IH) is a leading cause of obstruction of vascular
      interventions, including arterial stents, bypass grafts and arteriovenous grafts
      and fistulae. Proposals to account for arterial stent-associated IH include wall
      damage, low wall shear stress (WSS), disturbed flow and, although not widely
      recognized, wall hypoxia. The common non-planarity of arterial geometry and flow,
      led us to develop a bare-metal, nitinol, self-expanding stent with three
      dimensional helical-centreline geometry. This was deployed in one common carotid
      artery of healthy pigs, with a straight-centreline, but otherwise identical
      (conventional) stent deployed contralaterally. Both stent types deformed the
      arteries, but the helical-centreline device additionally deformed them helically
      and caused swirling of intraluminal flow. At sacrifice, one month post stent
      deployment, histology revealed significantly less IH in the helical-centreline
      than straight-centreline stented vessels. Medial cross-sectional area was not
      significantly different in helical-centreline than straight-centreline stented
      vessels. By contrast, luminal cross-sectional area was significantly larger in
      helical-centreline than straight-centreline stented vessels. Mechanisms
      considered to account for those results include enhanced intraluminal WSS and
      enhanced intraluminal blood-vessel wall mass transport, including of oxygen, in
      the helical-centreline stented vessels. Consistent with the latter proposal,
      adventitial microvessel density was lower in the helical-centreline stented than
      straight-centreline stented vessels. 

PMID- 24132201
TI  - Impacts of light shading and nutrient enrichment geo-engineering approaches on
      the productivity of a stratified, oligotrophic ocean ecosystem.
AB  - Geo-engineering proposals to mitigate global warming have focused either on
      methods of carbon dioxide removal, particularly nutrient fertilization of plant
      growth, or on cooling the Earth's surface by reducing incoming solar radiation
      (shading). Marine phytoplankton contribute half the Earth's biological carbon
      fixation and carbon export in the ocean is modulated by the actions of microbes
      and grazing communities in recycling nutrients. Both nutrients and light are
      essential for photosynthesis, so understanding the relative influence of both
      these geo-engineering approaches on ocean ecosystem production and processes is
      critical to the evaluation of their effectiveness. In this paper, we investigate
      the relationship between light and nutrient availability on productivity in a
      stratified, oligotrophic subtropical ocean ecosystem using a one-dimensional
      water column model coupled to a multi-plankton ecosystem model, with the goal of
      elucidating potential impacts of these geo-engineering approaches on ecosystem
      production. We find that solar shading approaches can redistribute productivity
      in the water column but do not change total production. Macronutrient enrichment
      is able to enhance the export of carbon, although heterotrophic recycling reduces
      the efficiency of carbon export substantially over time. Our results highlight
      the requirement for a fuller consideration of marine ecosystem interactions and
      feedbacks, beyond simply the stimulation of surface blooms, in the evaluation of
      putative geo-engineering approaches. 

PMID- 24132202
TI  - An automated algorithm for online detection of fragmented QRS and identification
      of its various morphologies.
AB  - Fragmented QRS (f-QRS) has been proven to be an efficient biomarker for several
      diseases, including remote and acute myocardial infarction, cardiac sarcoidosis,
      non-ischaemic cardiomyopathy, etc. It has also been shown to have higher
      sensitivity and/or specificity values than the conventional markers (e.g. Q-wave,
      ST-elevation, etc.) which may even regress or disappear with time. Patients with
      such diseases have to undergo expensive and sometimes invasive tests for
      diagnosis. Automated detection of f-QRS followed by identification of its various
      morphologies in addition to the conventional ECG feature (e.g. P, QRS, T
      amplitude and duration, etc.) extraction will lead to a more reliable diagnosis,
      therapy and disease prognosis than the state-of-the-art approaches and thereby
      will be of significant clinical importance for both hospital-based and emerging
      remote health monitoring environments as well as for implanted ICD devices. An
      automated algorithm for detection of f-QRS from the ECG and identification of its
      various morphologies is proposed in this work which, to the best of our
      knowledge, is the first work of its kind. Using our recently proposed time-domain
      morphology and gradient-based ECG feature extraction algorithm, the QRS complex
      is extracted and discrete wavelet transform (DWT) with one level of
      decomposition, using the 'Haar' wavelet, is applied on it to detect the presence
      of fragmentation. Detailed DWT coefficients were observed to hypothesize the
      postulates of detection of all types of morphologies as reported in the
      literature. To model and verify the algorithm, PhysioNet's PTB database was used.
      Forty patients were randomly selected from the database and their ECG were
      examined by two experienced cardiologists and the results were compared with
      those obtained from the algorithm. Out of 40 patients, 31 were considered
      appropriate for comparison by two cardiologists, and it is shown that 334 out of
      372 (89.8%) leads from the chosen 31 patients complied favourably with our
      proposed algorithm. The sensitivity and specificity values obtained for the
      detection of f-QRS were 0.897 and 0.899, respectively. Automation will speed up
      the detection of fragmentation, reducing the human error involved and will allow
      it to be implemented for hospital-based remote monitoring and ICD devices. 

PMID- 24132203
TI  - A mathematical model of serotype replacement in pneumococcal carriage following
      vaccination.
AB  - A number of childhood vaccination programmes have recently introduced vaccination
      against Streptococcus pneumoniae, the pneumococcus, a major cause of pneumonia
      and meningitis. The pneumococcal conjugate vaccines (PCVs) that are currently in
      use only protect against some serotypes of the bacterium, and there is now strong
      evidence that those serotypes not included in the vaccine increase in prevalence
      among most vaccinated populations. We present a mathematical model for the
      dynamics of nasopharyngeal carriage of S. pneumoniae that allows for carriage
      with multiple serotypes. The model is used to predict the prevalence of vaccine
      type (VT) and non-VT (NVT) serotypes following the introduction of PCV. Parameter
      estimates for the model are obtained by maximum likelihood using pre-vaccination
      data from The Gambia. The model predicts that low (1, 6A and 9V) and medium (4,
      5, 7F, 14, 18C, 19A and 19F) prevalence serotypes can be eliminated through
      vaccination, but that the overall prevalence of carriage will be reduced only
      slightly because of an increase in the prevalence of NVT serotypes. Serotype
      replacement will be sequential, with high and medium prevalence NVT serotypes
      dominating initially, followed by an increase of serotypes of low prevalence. We
      examine the impact of a hypothetical vaccine that provides partial protection
      against all serotypes, and find that this reduces overall carriage, but is unable
      to eliminate low or medium prevalence serotypes. 

PMID- 24132204
TI  - Quantifying Waddington landscapes and paths of non-adiabatic cell fate decisions
      for differentiation, reprogramming and transdifferentiation.
AB  - Cellular differentiation, reprogramming and transdifferentiation are determined
      by underlying gene regulatory networks. Non-adiabatic regulation via slow
      binding/unbinding to the gene can be important in these cell fate decision-making
      processes. Based on a stem cell core gene network, we uncovered the stem cell
      developmental landscape. As the binding/unbinding speed decreases, the landscape
      topography changes from bistable attractors of stem and differentiated states to
      more attractors of stem and other different cell states as well as substates. Non
      adiabaticity leads to more differentiated cell types and provides a natural
      explanation for the heterogeneity observed in the experiments. We quantified
      Waddington landscapes with two possible cell fate decision mechanisms by changing
      the regulation strength or regulation timescale (non-adiabaticity). Transition
      rates correlate with landscape topography through barrier heights between
      different states and quantitatively determine global stability. We found the
      optimal speeds of these cell fate decision-making processes. We quantified
      biological paths and predict that differentiation and reprogramming go through an
      intermediate state (IM1), whereas transdifferentiation goes through another
      intermediate state (IM2). Some predictions are confirmed by recent experimental
      studies. 

PMID- 24132205
TI  - Wing and body motion and aerodynamic and leg forces during take-off in
      droneflies.
AB  - Here, we present a detailed analysis of the take-off mechanics in droneflies
      performing voluntary take-offs. Wing and body kinematics of the insects during
      take-off were measured using high-speed video techniques. Based on the measured
      data, the inertia force acting on the insect was computed and the aerodynamic
      force of the wings was calculated by the method of computational fluid dynamics.
      Subtracting the aerodynamic force and the weight from the inertia force gave the
      leg force. In take-off, a dronefly increases its stroke amplitude gradually in
      the first 10-14 wingbeats and becomes airborne at about the 12th wingbeat. The
      aerodynamic force increases monotonously from zero to a value a little larger
      than its weight, and the leg force decreases monotonously from a value equal to
      its weight to zero, showing that the droneflies do not jump and only use
      aerodynamic force of flapping wings to lift themselves into the air. Compared
      with take-offs in insects in previous studies, in which a very large force (5-10
      times of the weight) generated either by jumping legs (locusts, milkweed bugs and
      fruit flies) or by the 'fling' mechanism of the wing pair (butterflies) is used
      in a short time, the take-off in the droneflies is relatively slow but smoother. 

PMID- 24132207
TI  - Disulfide exchange: exposing supramolecular reactivity through dynamic covalent
      chemistry.
AB  - A Tutorial Review of the subtle supramolecular interactions influencing the
      outcomes of equilibrating systems, focusing on the dynamic covalent chemistry
      (DCC) of disulfide exchange reactions, is presented. We discuss the topics of
      cation-pi interactions (2.1), hydrophobic effects (2.2), hydrogen bonding
      interactions (2.3) aromatic donor-acceptor interactions (2.4), and metal-ligand
      interactions (2.5) in the context of dynamic disulfide chemistry. 

PMID- 24132206
TI  - Asymmetric phospholipid: lipopolysaccharide bilayers; a Gram-negative bacterial
      outer membrane mimic.
AB  - The Gram-negative bacterial outer membrane (OM) is a complex and highly
      asymmetric biological barrier but the small size of bacteria has hindered
      advances in in vivo examination of membrane dynamics. Thus, model OMs, amenable
      to physical study, are important sources of data. Here, we present data from
      asymmetric bilayers which emulate the OM and are formed by a simple two-step
      approach. The bilayers were deposited on an SiO2 surface by Langmuir-Blodgett
      deposition of phosphatidylcholine as the inner leaflet and, via Langmuir-Schaefer
      deposition, an outer leaflet of either Lipid A or Escherichia coli rough
      lipopolysaccharides (LPS). The membranes were examined using neutron
      reflectometry (NR) to examine the coverage and mixing of lipids between the
      bilayer leaflets. NR data showed that in all cases, the initial deposition
      asymmetry was mostly maintained for more than 16 h. This stability enabled the
      sizes of the headgroups and bilayer roughness of 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine and Lipid A, Rc-LPS and Ra-LPS to be clearly resolved. The results
      show that rough LPS can be manipulated like phospholipids and used to fabricate
      advanced asymmetric bacterial membrane models using well-known bilayer deposition
      techniques. Such models will enable OM dynamics and interactions to be studied
      under in vivo-like conditions. 

PMID- 24132209
TI  - Effects of chronic kidney disease and uremia on hepatic drug metabolism and
      transport.
AB  - The pharmacokinetics of non-renally cleared drugs in patients with chronic kidney
      disease is often unpredictable. Some of this variability may be due to
      alterations in the expression and activity of extra renal drug-metabolizing
      enzymes and transporters, primarily localized in the liver and intestine. Studies
      conducted in rodent models of renal failure have shown decreased mRNA and protein
      expression of many members of the cytochrome P450 enzyme (CYP) gene family and
      the ATP-binding cassette (ABC) and solute carrier (SLC) gene families of drug
      transporters. Uremic toxins interfere with transcriptional activation, cause
      downregulation of gene expression mediated by proinflammatory cytokines, and
      directly inhibit the activity of the cytochrome P450s and drug transporters.
      While much has been learned about the effects of kidney disease on non-renal drug
      disposition, important questions remain regarding the mechanisms of these
      effects, as well as the interplay between drug-metabolizing enzymes and drug
      transporters in the uremic milieu. In this review, we have highlighted the
      existing gaps in our knowledge and understanding of the impact of chronic kidney
      disease on non-renal drug clearance, and identified areas of opportunity for
      future research. 

PMID- 24132212
TI  - Radiation induced physicochemical changes in FAP (fluoro alkyl phosphate) based
      imidazolium ionic liquids and their mechanistic pathways: influence of hydroxyl
      group functionalization of the cation.
AB  - Future applications of ionic liquids (ILs) in a variety of areas, especially
      those having high radiation fields such as the nuclear fuel cycle and in space
      technology, are under serious consideration nowadays. For such applications to be
      possible, however, radiation stability of the ILs is an important issue that
      needs to be addressed. We envisaged that the ultra-hydrophobic, bulky and
      hydrolytically stable FAP (tris(perfluoroalkyl)trifluorophosphate) anion might
      shield the radiolytically vulnerable imidazolium cations from degradation and our
      result shows that these anions indeed enhance their radiolytic stability.
      However, introduction of a hydroxyl group into the alkyl side chain of the
      imidazolium moiety resulted in significant changes in the physical properties of
      the IL with respect to onset temperatures, conductivity and the electrochemical
      window. Furthermore, a nonlinear trend in absorbance with an increase in
      radiation dose accompanied by NMR (nuclear magnetic resonance) and mass
      spectrometry studies clearly demonstrated that the presence of the hydroxyl group
      promotes various degradation channels. Interestingly, a perturbation of the
      hydrogen bond between the hydroxyl group (present in the side chain of the
      cation) and the fluorine atom of the anion (OHF) was evident in the case of
      irradiated hydroxyl functionalized FAP ILs. Besides, the hydrogen gas yields of
      the ILs were determined and found to be comparable to those of a radiolytically
      stable aromatic compound, benzene. Finally, through transient spectroscopic
      studies we could delineate the mechanism of the radiation induced changes in the
      physicochemical properties of the non-hydroxyl and hydroxyl containing FAP ILs.
      We have clearly demonstrated that a simple functionalization of the molecular
      structure of the FAP based imidazolium ILs might cause marked differences in the
      reactivity, reaction center and the nature of the radiolytic products, which
      eventually lead to significant changes in their physicochemical properties. 

PMID- 24132213
TI  - A new vision for Acta Crystallographica Section A.

PMID- 24132210
TI  - Increased mitochondrial activity in renal proximal tubule cells from young
      spontaneously hypertensive rats.
AB  - Renal proximal tubule cells from spontaneously hypertensive rats (SHR), compared
      with normotensive Wistar-Kyoto rats (WKY), have increased oxidative stress. The
      contribution of mitochondrial oxidative phosphorylation to the subsequent
      hypertensive phenotype remains unclear. We found that renal proximal tubule cells
      from SHR, relative to WKY, had significantly higher basal oxygen consumption
      rates, adenosine triphosphate synthesis-linked oxygen consumption rates, and
      maximum and reserve respiration. These bioenergetic parameters indicated
      increased mitochondrial function in renal proximal tubule cells from SHR compared
      with WKY. Pyruvate dehydrogenase complex activity was consistently higher in both
      renal proximal tubule cells and cortical homogenates from SHR than those from
      WKY. Treatment for 6 days with dichloroacetate, an inhibitor of pyruvate
      dehydrogenase kinase, significantly increased renal pyruvate dehydrogenase
      complex activity and systolic blood pressure in 3-week-old WKY and SHR.
      Therefore, mitochondrial oxidative phosphorylation is higher in renal proximal
      tubule cells from SHR compared with WKY. Thus, the pyruvate dehydrogenase complex
      is a determinant of increased mitochondrial metabolism that could be a causal
      contributor to the hypertension in SHR. 

PMID- 24132214
TI  - Nets with collisions (unstable nets) and crystal chemistry.
AB  - Nets in which different vertices have identical barycentric coordinates (i.e.
      have collisions) are called unstable. Some such nets have automorphisms that do
      not correspond to crystallographic symmetries and are called non
      crystallographic. Examples are given of nets taken from real crystal structures
      which have embeddings with crystallographic symmetry in which colliding nodes
      either are, or are not, topological neighbors (linked) and in which some links
      coincide. An example is also given of a crystallographic net of exceptional girth
      (16), which has collisions in barycentric coordinates but which also has
      embeddings without collisions with the same symmetry. In this last case the
      collisions are termed unforced. 

PMID- 24132215
TI  - Homometry in the light of coherent beams.
AB  - Two systems are homometric if they are indistinguishable by diffraction. A
      distinction is first made between Bragg and diffuse scattering homometry, and it
      is shown that in the last case coherent diffraction can allow the diffraction
      diagrams to be differentiated. The study of the Rudin-Shapiro sequence,
      homometric to random sequences, allows one to manipulate independently two-point
      and four-point correlation functions, and to show their effect on the statistics
      of speckle patterns. This study provides evidence that long-range order in high
      order correlation functions has a measurable effect on the speckle statistics. 

PMID- 24132216
TI  - More about residual values.
AB  - The usual residual values are complemented by expectation values based solely on
      the experimental data and the number of model parameters. These theoretical R
      values serve as benchmark values when all of the basic assumptions for a least
      squares refinement, i.e. no systematic errors and a fully adequate model capable
      of describing the data, are fulfilled. The prediction of R values as presented
      here is applicable to any field where model parameters are fitted to data with
      known precision. For crystallographic applications, F(2)-based residual benchmark
      values are given. They depend on the first and second moments of variance,
      intensity and significance distributions, <sigma(2)>, <Io(2)>, <Io(2)/sigma(2)>.
      Possible applications of the theoretical R values are, for example, as a data
      quality measure or the detection of systematic deviations between experimental
      data and model predicted data, although the theoretical R values cannot identify
      the origin of these systematic deviations. The change in R values due to
      application of a weighting scheme is quantified with the theoretical R values.

PMID- 24132217
TI  - Direct phasing of nanocrystal diffraction.
AB  - Recent experiments at free-electron laser X-ray sources have been able to resolve
      the intensity distributions about Bragg peaks in nanocrystals of large
      biomolecules. Information derived from small shifts in the peak positions augment
      the Bragg samples of the particle intensity with samples of its gradients.
      Working on the assumption that the nanocrystal is entirely generated by lattice
      translations of a particle, an algorithm is developed that reconstructs the
      particle from intensities and intensity gradients. Unlike traditional direct
      phasing methods that require very high resolution data in order to exploit
      sparsity of the electron density, this method imposes no constraints on the
      contrast other than positivity and works well at low resolution. Successful
      reconstructions are demonstrated with simulated P1 lysozyme nanocrystal data down
      to a signal-to-noise ratio of 2 in the intensity gradients. 

PMID- 24132218
TI  - Comparative study of X-ray charge-density data on CoSb3.
AB  - CoSb3 is an example of a highly challenging case for experimental charge-density
      analysis due to the heavy elements (suitability factor of ~0.01), the perfect
      crystallinity and the high symmetry of the compound. It is part of a family of
      host-guest structures that are potential candidates for use as high-performance
      thermoelectric materials. Obtaining and analysing accurate charge densities of
      the undoped host structure potentially can improve the understanding of the
      thermoelectric properties of this family of materials. In a previous study,
      analysis of the electron density gave a picture of covalent Co-Sb and Sb-Sb
      interactions together with relatively low atomic charges based on state-of-the
      art experimental and theoretical data. In the current study, several experimental
      X-ray diffraction data sets collected on the empty CoSb3 framework are compared
      in order to probe the experimental requirements for obtaining data of high enough
      quality for charge-density analysis even in the case of very unsuitable crystals.
      Furthermore, the quality of the experimental structure factors is tested by
      comparison with theoretical structure factors obtained from periodic DFT
      calculations. The results clearly show that, in the current study, the data
      collected on high-intensity, high-energy synchrotron sources and very small
      crystals are superior to data collected at conventional sources, and in fact
      necessary for a meaningful charge-density study, primarily due to greatly
      diminished effects of extinction and absorption which are difficult to correct
      for with sufficient accuracy.

PMID- 24132219
TI  - C70, C80, C90 and carbon nanotubes by breaking of the icosahedral symmetry of
      C60.
AB  - The icosahedral symmetry group H3 of order 120 and its dihedral subgroup H2 of
      order 10 are used for exact geometric construction of polytopes that are known to
      exist in nature. The branching rule for the H3 orbit of the fullerene C60 to the
      subgroup H2 yields a union of eight orbits of H2: four of them are regular
      pentagons and four are regular decagons. By inserting into the branching rule
      one, two, three or n additional decagonal orbits of H2, one builds the polytopes
      C70, C80, C90 and nanotubes in general. A minute difference should be taken into
      account depending on whether an even or odd number of H2 decagons are inserted.
      Vertices of all the structures are given in exact coordinates relative to a non
      orthogonal basis naturally appropriate for the icosahedral group, as well as
      relative to an orthonormal basis. Twisted fullerenes are defined. Their surface
      consists of 12 regular pentagons and 20 hexagons that have three and three edges
      of equal length. There is an uncountable number of different twisted fullerenes,
      all with precise icosahedral symmetry. Two examples of the twisted C60 are
      described. 

PMID- 24132220
TI  - Platonic solids generate their four-dimensional analogues.
AB  - This paper shows how regular convex 4-polytopes - the analogues of the Platonic
      solids in four dimensions - can be constructed from three-dimensional
      considerations concerning the Platonic solids alone. Via the Cartan-Dieudonne
      theorem, the reflective symmetries of the Platonic solids generate rotations. In
      a Clifford algebra framework, the space of spinors generating such three
      dimensional rotations has a natural four-dimensional Euclidean structure. The
      spinors arising from the Platonic solids can thus in turn be interpreted as
      vertices in four-dimensional space, giving a simple construction of the four
      dimensional polytopes 16-cell, 24-cell, the F4 root system and the 600-cell. In
      particular, these polytopes have 'mysterious' symmetries, that are almost trivial
      when seen from the three-dimensional spinorial point of view. In fact, all these
      induced polytopes are also known to be root systems and thus generate rank-4
      Coxeter groups, which can be shown to be a general property of the spinor
      construction. These considerations thus also apply to other root systems such as
      A(1)?oplus I(2)(n) which induces I(2)(n)?oplus I(2)(n), explaining the existence
      of the grand antiprism and the snub 24-cell, as well as their symmetries. These
      results are discussed in the wider mathematical context of Arnold's trinities and
      the McKay correspondence. These results are thus a novel link between the
      geometries of three and four dimensions, with interesting potential applications
      on both sides of the correspondence, to real three-dimensional systems with
      polyhedral symmetries such as (quasi)crystals and viruses, as well as four
      dimensional geometries arising for instance in Grand Unified Theories and string
      and M-theory.

PMID- 24132221
TI  - Distribution rules of systematic absences on the Conway topograph and their
      application to powder auto-indexing.
AB  - This paper presents several general properties of systematic absences that are
      available before unit-cell parameters and the space group have been determined.
      The properties are given in the form of distribution rules of Miller indices
      corresponding to systematic absences on a topograph. A topograph is a graph whose
      edges are associated with a set of four lattice vectors satisfying Ito's equation
      2(|l1(*)|(2) + |l2(*)|(2)) = |l1(*) + l2(*)|(2) + |l1(*) - l2(*)|(2). It is
      possible to integrate global information about extinct reflections by using
      topographs. As an example of the application of these rules, a new powder auto
      indexing algorithm is introduced, focusing on its theoretical aspects.

PMID- 24132222
TI  - Spin line groups.
AB  - Spin line groups describe the symmetries of spin arrangements in quasi-one
      dimensional systems. These groups are derived for the first family of line
      groups. Among them, magnetic groups are singled out as a special case. Spin
      arrangements generated by the derived groups are first discussed for single-orbit
      systems and then the conclusions are extended to multi-orbit cases. The results
      are illustrated by the examples of a CuO2 zigzag chain, a (13)C nanotube and the
      hexaferrite Ba2Mg2Fe12O22. Applications to neutron diffraction and classical
      ground-state determination are indicated. 

PMID- 24132225
TI  - Copper-catalyzed C(sp2)-H amidation of unactivated arenes by N
      tosyloxycarbamates.
AB  - [(Neocuproine)Cu]PF6 catalyzes the C-H amidation of unactivated arenes by N
      tosyloxytrichloroethylcarbamates. Alkyl benzenes are selectively converted to
      aromatic amines and substituted arenes display variable regioselectivity. 

PMID- 24132226
TI  - Melatonin and stable circadian rhythms optimize maternal, placental and fetal
      physiology.
AB  - BACKGROUND: Research within the last decade has shown melatonin to have
      previously-unsuspected beneficial actions on the peripheral reproductive organs.
      Likewise, numerous investigations have documented that stable circadian rhythms
      are also helpful in maintaining reproductive health. The relationship of
      melatonin and circadian rhythmicity to maternal and fetal health is summarized in
      this review. METHODS: Databases were searched for the related published English
      literature up to 15 May 2013. The search terms used in various combinations
      included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus,
      ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth
      restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative
      stress and free radicals. The results of the studies uncovered are summarized
      herein. RESULTS: Both melatonin and circadian rhythms impact reproduction,
      especially during pregnancy. Melatonin is a multifaceted molecule with direct
      free radical scavenging and indirect antioxidant activities. Melatonin is
      produced in both the ovary and in the placenta where it protects against
      molecular mutilation and cellular dysfunction arising from oxidative/nitrosative
      stress. The placenta, in particular, is often a site of excessive free radical
      generation due to less than optimal adhesion to the uterine wall, which leads to
      either persistent hypoxia or intermittent hypoxia and reoxygenation, processes
      that cause massive free radical generation and organ dysfunction. This may
      contribute to pre-eclampsia and other disorders which often complicate pregnancy.
      Melatonin has ameliorated free radical damage to the placenta and to the fetus in
      experiments using non-human mammals. Likewise, the maintenance of a regular
      maternal light/dark and sleep/wake cycle is important to stabilize circadian
      rhythms generated by the maternal central circadian pacemaker, the
      suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important
      since her circadian clock, either directly or indirectly via the melatonin
      rhythm, programs the developing master oscillator of the fetus. Experimental
      studies have shown that disturbed maternal circadian rhythms, referred to as
      chronodisruption, and perturbed melatonin cycles have negative consequences for
      the maturing fetal oscillators, which may lead to psychological and behavioral
      problems in the newborn. To optimize regular circadian rhythms and prevent
      disturbances of the melatonin cycle during pregnancy, shift work and bright light
      exposure at night should be avoided, especially during the last trimester of
      pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the
      fetus. Since blood melatonin levels are normally highest during the dark period,
      the propensity of childbirth to occur at night may relate to the high levels of
      melatonin at this time which work in concert with oxytocin to enhance the
      strength of uterine contractions. CONCLUSIONS: A number of conclusions naturally
      evolve from the data summarized in this review: (i) melatonin, of both pineal and
      placental origin, has essential functions in fetal maturation and
      placenta/uterine homeostasis; (ii) circadian clock genes, which are components of
      all cells including those in the peripheral reproductive organs, have important
      roles in reproductive and organismal (fetal and maternal) physiology; (iii) due
      to the potent antioxidant actions of melatonin, coupled with its virtual absence
      of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia,
      intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc.
      (iv) the propensity for parturition to occur at night may relate to the synergism
      between the nocturnal increase in melatonin and oxytocin.

PMID- 24132227
TI  - Two novel six-coordinated cadmium(II) and zinc(II) complexes from carbazate beta
      diketonate: crystal structures, enhanced two-photon absorption and biological
      imaging application.
AB  - To explore the photophysical properties of coordination compounds with enhanced
      two-photon absorption, two novel six-coordinated metal complexes (ML2, M =
      Cd(ii), Zn(ii)) from carbazole beta-diketone ligand (HL = 4,4,4-trifluoro-1-(9
      butylcarbazole-3-yl)-1,3-butanedione) were prepared and fully characterized.
      Their crystal structures were determined by X-ray diffraction analysis. Both
      variable temperature (1)H NMR spectra and MALDI-TOF mass spectrometry proved that
      the coordination compounds exhibit good stability in solution. The results of
      time-dependent density functional theory (TD-DFT) calculations indicated that the
      complexation of the ligands with metal ion extends the electronic delocalization
      in the coordination compounds, leading to enhanced two-photon absorption. The
      photophysical properties for the coordination compounds were identified relying
      on both experimentally and theoretically studies. Finally, confocal microscopy
      and two-photon microscopy fluorescent imaging of HepG2 cells labeled with the
      Zn(ii) complexe revealed its potential applications as a biological fluorescent
      probe. 

PMID- 24132228
TI  - An InN/InGaN quantum dot electrochemical biosensor for clinical diagnosis.
AB  - Low-dimensional InN/InGaN quantum dots (QDs) are demonstrated for realizing
      highly sensitive and efficient potentiometric biosensors owing to their unique
      electronic properties. The InN QDs are biochemically functionalized. The
      fabricated biosensor exhibits high sensitivity of 97 mV/decade with fast output
      response within two seconds for the detection of cholesterol in the logarithmic
      concentration range of 1 * 10-6 M to 1 * 10-3 M. The selectivity and reusability
      of the biosensor are excellent and it shows negligible response to common
      interferents such as uric acid and ascorbic acid. We also compare the biosensing
      properties of the InN QDs with those of an InN thin film having the same surface
      properties, i.e., high density of surface donor states, but different morphology
      and electronic properties. The sensitivity of the InN QDs-based biosensor is
      twice that of the InN thin film-based biosensor, the EMF is three times larger,
      and the response time is five times shorter. A bare InGaN layer does not produce
      a stable response. Hence, the superior biosensing properties of the InN QDs are
      governed by their unique surface properties together with the zero-dimensional
      electronic properties. Altogether, the InN QDs-based biosensor reveals great
      potential for clinical diagnosis applications.

PMID- 24132230
TI  - Biodiversity assessment using hierarchical agglomerative clustering and spectral
      unmixing over hyperspectral images.
AB  - Hyperspectral images represent an important source of information to assess
      ecosystem biodiversity. In particular, plant species richness is a primary
      indicator of biodiversity. This paper uses spectral variance to predict
      vegetation richness, known as Spectral Variation Hypothesis. Hierarchical
      agglomerative clustering is our primary tool to retrieve clusters whose Shannon
      entropy should reflect species richness on a given zone. However, in a high
      spectral mixing scenario, an additional unmixing step, just before entropy
      computation, is required; cluster centroids are enough for the unmixing process.
      Entropies computed using the proposed method correlate well with the ones
      calculated directly from synthetic and field data. 

PMID- 24132229
TI  - Recent advances in optical biosensors for environmental monitoring and early
      warning.
AB  - The growing number of pollutants requires the development of innovative
      analytical devices that are precise, sensitive, specific, rapid, and easy-to-use
      to meet the increasing demand for legislative actions on environmental pollution
      control and early warning. Optical biosensors, as a powerful alternative to
      conventional analytical techniques, enable the highly sensitive, real-time, and
      high-frequency monitoring of pollutants without extensive sample preparation.
      This article reviews important advances in functional biorecognition materials
      (e.g., enzymes, aptamers, DNAzymes, antibodies and whole cells) that facilitate
      the increasing application of optical biosensors. This work further examines the
      significant improvements in optical biosensor instrumentation and their
      environmental applications. Innovative developments of optical biosensors for
      environmental pollution control and early warning are also discussed. 

PMID- 24132231
TI  - Resonant transparency and non-trivial non-radiating excitations in toroidal
      metamaterials.
AB  - Engaging strongly resonant interactions allows dramatic enhancement of
      functionalities of many electromagnetic devices. However, resonances can be
      dampened by Joule and radiation losses. While in many cases Joule losses may be
      minimized by the choice of constituting materials, controlling radiation losses
      is often a bigger problem. Recent solutions include the use of coupled radiant
      and sub-radiant modes yielding narrow asymmetric Fano resonances in a wide range
      of systems, from defect states in photonic crystals and optical waveguides with
      mesoscopic ring resonators to nanoscale plasmonic and metamaterial systems
      exhibiting interference effects akin to electromagnetically-induced transparency.
      Here we demonstrate theoretically and confirm experimentally a new mechanism of
      resonant electromagnetic transparency, which yields very narrow isolated
      symmetric Lorentzian transmission lines in toroidal metamaterials. It exploits
      the long sought non-trivial non-radiating charge-current excitation based on
      interfering electric and toroidal dipoles that was first proposed by Afanasiev
      and Stepanovsky in [J. Phys. A Math. Gen. 28, 4565 (1995)].

PMID- 24132232
TI  - Exploiting dimensionality and defect mitigation to create tunable microwave
      dielectrics.
AB  - The miniaturization and integration of frequency-agile microwave circuits-
      relevant to electronically tunable filters, antennas, resonators and phase
      shifters--with microelectronics offers tantalizing device possibilities, yet
      requires thin films whose dielectric constant at gigahertz frequencies can be
      tuned by applying a quasi-static electric field. Appropriate systems such as
      BaxSr1-xTiO3 have a paraelectric-ferroelectric transition just below ambient
      temperature, providing high tunability. Unfortunately, such films suffer
      significant losses arising from defects. Recognizing that progress is stymied by
      dielectric loss, we start with a system with exceptionally low loss-
      Srn+1TinO3n+1 phases--in which (SrO)2 crystallographic shear planes provide an
      alternative to the formation of point defects for accommodating non
      stoichiometry. Here we report the experimental realization of a highly tunable
      ground state arising from the emergence of a local ferroelectric instability in
      biaxially strained Srn+1TinO3n+1 phases with n >= 3 at frequencies up to 125 GHz.
      In contrast to traditional methods of modifying ferroelectrics-doping or strain
      in this unique system an increase in the separation between the (SrO)2 planes,
      which can be achieved by changing n, bolsters the local ferroelectric
      instability. This new control parameter, n, can be exploited to achieve a figure
      of merit at room temperature that rivals all known tunable microwave dielectrics.

PMID- 24132233
TI  - The earliest known holometabolous insects.
AB  - The Eumetabola (Endopterygota (also known as Holometabola) plus Paraneoptera)
      have the highest number of species of any clade, and greatly contribute to animal
      species biodiversity. The palaeoecological circumstances that favoured their
      emergence and success remain an intriguing question. Recent molecular
      phylogenetic analyses have suggested a wide range of dates for the initial
      appearance of the Holometabola, from the Middle Devonian epoch (391 million years
      (Myr) ago) to the Late Pennsylvanian epoch (311 Myr ago), and Hemiptera (310 Myr
      ago). Palaeoenvironments greatly changed over these periods, with global cooling
      and increasing complexity of green forests. The Pennsylvanian-period crown
      eumetabolan fossil record remains notably incomplete, particularly as several
      fossils have been erroneously considered to be stem Holometabola (Supplementary
      Information); the earliest definitive beetles are from the start of the Permian
      period. The emergence of the hymenopterids, sister group to other Holometabola,
      is dated between 350 and 309 Myr ago, incongruent with their current earliest
      record (Middle Triassic epoch). Here we describe five fossils--a Gzhelian-age
      stem coleopterid, a holometabolous larva of uncertain ordinal affinity, a stem
      hymenopterid, and early Hemiptera and Psocodea, all from the Moscovian age--and
      reveal a notable penecontemporaneous breadth of early eumetabolan insects. These
      discoveries are more congruent with current hypotheses of clade divergence.
      Eumetabola experienced episodes of diversification during the Bashkirian
      Moscovian and the Kasimovian-Gzhelian ages. This cladogenetic activity is perhaps
      related to notable episodes of drying resulting from glaciations, leading to the
      eventual demise in Euramerica of coal-swamp ecosystems, evidenced by floral
      turnover during this interval. These ancient species were of very small size,
      living in the shadow of Palaeozoic-era 'giant' insects. Although these
      discoveries reveal unexpected Pennsylvanian eumetabolan diversity, the lineage
      radiated more successfully only after the mass extinctions at the end of the
      Permian period, giving rise to the familiar crown groups of their respective
      clades.

PMID- 24132234
TI  - LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent
      dystrophy.
AB  - The dense glycan coat that surrounds every cell is essential for cellular
      development and physiological function, and it is becoming appreciated that its
      composition is highly dynamic. Post-translational addition of the polysaccharide
      repeating unit [-3-xylose-alpha1,3-glucuronic acid-beta1-]n by like
      acetylglucosaminyltransferase (LARGE) is required for the glycoprotein
      dystroglycan to function as a receptor for proteins in the extracellular matrix.
      Reductions in the amount of [-3-xylose-alpha1,3-glucuronic acid-beta1-]n
      (hereafter referred to as LARGE-glycan) on dystroglycan result in heterogeneous
      forms of muscular dystrophy. However, neither patient nor mouse studies has
      revealed a clear correlation between glycosylation status and phenotype. This
      disparity can be attributed to our lack of knowledge of the cellular function of
      the LARGE-glycan repeat. Here we show that coordinated upregulation of Large and
      dystroglycan in differentiating mouse muscle facilitates rapid extension of LARGE
      glycan repeat chains. Using synthesized LARGE-glycan repeats we show a direct
      correlation between LARGE-glycan extension and its binding capacity for
      extracellular matrix ligands. Blocking Large upregulation during muscle
      regeneration results in the synthesis of dystroglycan with minimal LARGE-glycan
      repeats in association with a less compact basement membrane, immature
      neuromuscular junctions and dysfunctional muscle predisposed to dystrophy. This
      was consistent with the finding that patients with increased clinical severity of
      disease have fewer LARGE-glycan repeats. Our results reveal that the LARGE-glycan
      of dystroglycan serves as a tunable extracellular matrix protein scaffold, the
      extension of which is required for normal skeletal muscle function. 

PMID- 24132235
TI  - Precision is essential for efficient catalysis in an evolved Kemp eliminase.
AB  - Linus Pauling established the conceptual framework for understanding and
      mimicking enzymes more than six decades ago. The notion that enzymes selectively
      stabilize the rate-limiting transition state of the catalysed reaction relative
      to the bound ground state reduces the problem of design to one of molecular
      recognition. Nevertheless, past attempts to capitalize on this idea, for example
      by using transition state analogues to elicit antibodies with catalytic
      activities, have generally failed to deliver true enzymatic rates. The advent of
      computational design approaches, combined with directed evolution, has provided
      an opportunity to revisit this problem. Starting from a computationally designed
      catalyst for the Kemp elimination--a well-studied model system for proton
      transfer from carbon--we show that an artificial enzyme can be evolved that
      accelerates an elementary chemical reaction 6 * 10(8)-fold, approaching the
      exceptional efficiency of highly optimized natural enzymes such as
      triosephosphate isomerase. A 1.09 A resolution crystal structure of the evolved
      enzyme indicates that familiar catalytic strategies such as shape complementarity
      and precisely placed catalytic groups can be successfully harnessed to afford
      such high rate accelerations, making us optimistic about the prospects of
      designing more sophisticated catalysts.

PMID- 24132236
TI  - The origin of conodonts and of vertebrate mineralized skeletons.
AB  - Conodonts are an extinct group of jawless vertebrates whose tooth-like elements
      are the earliest instance of a mineralized skeleton in the vertebrate lineage,
      inspiring the 'inside-out' hypothesis that teeth evolved independently of the
      vertebrate dermal skeleton and before the origin of jaws. However, these
      propositions have been based on evidence from derived euconodonts. Here we test
      hypotheses of a paraconodont ancestry of euconodonts using synchrotron radiation
      X-ray tomographic microscopy to characterize and compare the microstructure of
      morphologically similar euconodont and paraconodont elements. Paraconodonts
      exhibit a range of grades of structural differentiation, including tissues and a
      pattern of growth common to euconodont basal bodies. The different grades of
      structural differentiation exhibited by paraconodonts demonstrate the stepwise
      acquisition of euconodont characters, resolving debate over the relationship
      between these two groups. By implication, the putative homology of euconodont
      crown tissue and vertebrate enamel must be rejected as these tissues have evolved
      independently and convergently. Thus, the precise ontogenetic, structural and
      topological similarities between conodont elements and vertebrate odontodes
      appear to be a remarkable instance of convergence. The last common ancestor of
      conodonts and jawed vertebrates probably lacked mineralized skeletal tissues. The
      hypothesis that teeth evolved before jaws and the inside-out hypothesis of dental
      evolution must be rejected; teeth seem to have evolved through the extension of
      odontogenic competence from the external dermis to internal epithelium soon after
      the origin of jaws. 

PMID- 24132238
TI  - Palaeontology: Inside-out turned upside-down.

PMID- 24132239
TI  - Applied physics: Materials scientists take control.

PMID- 24132237
TI  - Inhibitory signalling to the Arp2/3 complex steers cell migration.
AB  - Cell migration requires the generation of branched actin networks that power the
      protrusion of the plasma membrane in lamellipodia. The actin-related proteins 2
      and 3 (Arp2/3) complex is the molecular machine that nucleates these branched
      actin networks. This machine is activated at the leading edge of migrating cells
      by Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein
      (WAVE, also known as SCAR). The WAVE complex is itself directly activated by the
      small GTPase Rac, which induces lamellipodia. However, how cells regulate the
      directionality of migration is poorly understood. Here we identify a new protein,
      Arpin, that inhibits the Arp2/3 complex in vitro, and show that Rac signalling
      recruits and activates Arpin at the lamellipodial tip, like WAVE. Consistently,
      after depletion of the inhibitory Arpin, lamellipodia protrude faster and cells
      migrate faster. A major role of this inhibitory circuit, however, is to control
      directional persistence of migration. Indeed, Arpin depletion in both mammalian
      cells and Dictyostelium discoideum amoeba resulted in straighter trajectories,
      whereas Arpin microinjection in fish keratocytes, one of the most persistent
      systems of cell migration, induced these cells to turn. The coexistence of the
      Rac-Arpin-Arp2/3 inhibitory circuit with the Rac-WAVE-Arp2/3 activatory circuit
      can account for this conserved role of Arpin in steering cell migration. 

PMID- 24132240
TI  - SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome
      patients.
AB  - Phelan-McDermid syndrome (PMDS) is a complex neurodevelopmental disorder
      characterized by global developmental delay, severely impaired speech,
      intellectual disability, and an increased risk of autism spectrum disorders
      (ASDs). PMDS is caused by heterozygous deletions of chromosome 22q13.3. Among the
      genes in the deleted region is SHANK3, which encodes a protein in the
      postsynaptic density (PSD). Rare mutations in SHANK3 have been associated with
      idiopathic ASDs, non-syndromic intellectual disability, and schizophrenia.
      Although SHANK3 is considered to be the most likely candidate gene for the
      neurological abnormalities in PMDS patients, the cellular and molecular
      phenotypes associated with this syndrome in human neurons are unknown. We
      generated induced pluripotent stem (iPS) cells from individuals with PMDS and
      autism and used them to produce functional neurons. We show that PMDS neurons
      have reduced SHANK3 expression and major defects in excitatory, but not
      inhibitory, synaptic transmission. Excitatory synaptic transmission in PMDS
      neurons can be corrected by restoring SHANK3 expression or by treating neurons
      with insulin-like growth factor 1 (IGF1). IGF1 treatment promotes formation of
      mature excitatory synapses that lack SHANK3 but contain PSD95 and N-methyl-D
      aspartate (NMDA) receptors with fast deactivation kinetics. Our findings provide
      direct evidence for a disruption in the ratio of cellular excitation and
      inhibition in PMDS neurons, and point to a molecular pathway that can be
      recruited to restore it.

PMID- 24132241
TI  - Profiling the iron, copper and zinc content in primary neuron and astrocyte
      cultures by rapid online quantitative size exclusion chromatography-inductively
      coupled plasma-mass spectrometry.
AB  - Metals often determine the chemical reactivity of the proteins to which they are
      bound. Each cell in the body tightly maintains a unique metalloproteomic profile,
      mostly dependent on function. This paper describes an analytical online flow
      injection quantitative size exclusion chromatography-inductively coupled plasma
      mass spectrometry (SEC-ICP-MS) method, which was applied to profiling the metal
      binding proteins found in primary cultures of neurons and astrocytes. This method
      can be conducted using similar amounts of sample to those used for Western
      blotting (20-150 MUg protein), and has a turnaround time of <15 minutes.
      Metalloprotein standards for Fe (as ferritin), Cu and Zn (as superoxide dismutase
      1) were used to construct multi-point calibration curves for online
      quantification of metalloproteins by SEC-ICP-MS. Homogenates of primary neuron
      and astrocyte cultures were analysed by SEC-ICP-MS. Online quantification by
      external calibration with metalloprotein standards determined the mass of metal
      eluting from the column relative to time (as pg s(-1)). Total on-column Fe, Cu
      and Zn detection limits ranged from 0.825 +/- 0.005 ng to 13.6 +/- 0.7 pg.
      Neurons and astrocytes exhibited distinct metalloprotein profiles, featuring both
      ubiquitous and unique metalloprotein species. Separation and detection by SEC-ICP
      MS allows appraisal of these metalloproteins in their native state, and online
      quantification was achieved using this relatively simple external calibration
      process. 

PMID- 24132242
TI  - Haemostasis in chronic kidney disease.
AB  - The coagulation system has gained much interest again as new anticoagulatory
      substances have been introduced into clinical practice. Especially patients with
      renal failure are likely candidates for such a therapy as they often experience
      significant comorbidity including cardiovascular diseases that require
      anticoagulation. Patients with renal failure on new anticoagulants have
      experienced excessive bleeding which can be related to a changed pharmacokinetic
      profile of the compounds. However, the coagulation system itself, even without
      any interference with coagulation modifying drugs, is already profoundly changed
      during renal failure. Coagulation disorders with either episodes of severe
      bleeding or thrombosis represent an important cause for the morbidity and
      mortality of such patients. The underlying reasons for these coagulation
      disorders involve the changed interaction of different components of the
      coagulation system such as the coagulation cascade, the platelets and the vessel
      wall in the metabolic conditions of renal failure. Recent work provides evidence
      that new factors such as microparticles (MPs) can influence the coagulation
      system in patients with renal insufficiency through their potent procoagulatory
      effects. Interestingly, MPs may also contain microRNAs thus inhibiting the
      function of platelets, resulting in bleeding episodes. This review comprises the
      findings on the complex pathophysiology of coagulation disorders including new
      factors such as MPs and microRNAs in patients with renal insufficiency. 

PMID- 24132243
TI  - Relationships of elevated systemic pentraxin-3 levels with high-risk coronary
      plaque components and impaired myocardial perfusion after percutaneous coronary
      intervention in patients with ST-elevation acute myocardial infarction.
AB  - BACKGROUND: We aimed to assess the relationships of pentraxin-3 (PTX3) with
      coronary plaque components and myocardial perfusion after percutaneous coronary
      intervention (PCI) in order to clarify the mechanisms underlying the prognostic
      function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients.
      METHODS AND RESULTS: We enrolled 75 STEMI patients who underwent pre-PCI virtual
      histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI
      PTX3 level with coronary plaque components and post-PCI myocardial blush grade
      (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median >=3.79ng/ml) had
      higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%,
      P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1)
      (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate
      analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1)
      (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9
      month follow-up, cardiac event-free survival was poorer for patients with post
      PCI MBG (0-1) (log-rank test chi(2)=8.6; P=0.003). Cox proportional-hazards
      analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309;
      P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409
      20.359; P=0.014) as independent predictors of adverse cardiac events during
      follow-up. CONCLUSIONS: Systemic pre-PCI PTX3 was associated with high-risk
      plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a
      reliable predictor of outcome in STEMI patients.

PMID- 24132244
TI  - Bone marrow rejuvenation. An excellent potential therapy for age-related
      endothelial dysfunction.

PMID- 24132247
TI  - Pseudopolyrotaxanes based polyhedral oligomeric silsesquioxanes and
      cucurbit[7]uril.
AB  - Pseudopolyrotaxanes (POSS/CB[7]) were synthesized using octaimidazolium-based
      polyhedral oligomeric silsesquioxanes (POSS) and cucurbit[7]uril (CB[7]) in
      aqueous solution. The binding interactions were monitored by (1)H NMR. Their
      regular octahedral morphologies were confirmed by TEM. The POSS/CB[7] was also
      characterized by FT-IR, thermogravimetric analysis (TGA), and elemental analysis.
      The TGA results show that the thermal stabilities of POSS/CB[7] can be improved
      by the threading of CB[7].

PMID- 24132245
TI  - Congruence between spouses' perceptions and observers' ratings of responsiveness:
      the role of attachment avoidance.
AB  - Although close relationships require partners to depend on one another for mutual
      responsiveness, avoidantly attached individuals are especially averse to risking
      such dependency. The authors propose that both avoidant and non-avoidant
      individuals perceive signs of their own and their partners' responsiveness in
      ways that reflect motivated perceptions of dependency. The present research
      examined how the interplay between spouses' attachment avoidance and observed
      responsive behaviors during marital conflict shaped perceptions of their own and
      their partners' responsiveness. Newlywed couples attempted to resolve a
      relationship conflict and then reported perceptions of their own and their
      partners' responsiveness during the conflict. Observers also coded both partners'
      responsive behaviors during the conflict. Avoidant spouses perceived themselves
      as less responsive, especially when observers rated them as more responsive;
      avoidant spouses also perceived their partners as less responsive. The discussion
      highlights the role of attachment in understanding links between responsiveness
      related perceptions and behaviors. 

PMID- 24132248
TI  - Galantamine efficacy and tolerability as an augmentative therapy in autistic
      children: A randomized, double-blind, placebo-controlled trial.
AB  - The role of cholinergic abnormalities in autism was recently evidenced and there
      is a growing interest in cholinergic modulation, emerging for targeting autistic
      symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric
      potentiator of nicotinic receptors. This study aimed to evaluate the possible
      effects of galantamine as an augmentative therapy to risperidone, in autistic
      children. In this randomized, double-blind, placebo-controlled, parallel-group
      study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR)
      and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C)
      Irritability subscale were equally randomized to receive either galantamine (up
      to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10
      weeks. We rated participants by ABC-C and a side effects checklist, at baseline
      and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients
      showed significantly greater improvement in the Irritability (P = 0.017) and
      Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The
      difference between the two groups in the frequency of side effects was not
      significant. In conclusion, galantamine augmentation was shown to be a relatively
      effective and safe augmentative strategy for alleviating some of the autism
      related symptoms. 

PMID- 24132250
TI  - Opinion dynamics with similarity-based random neighbors.
AB  - A typical assumption made in the existing opinion formation models is that two
      individuals can communicate with each other only if the distance between their
      opinions is less than a threshold called bound of confidence. However, in the
      real world it is quite possible that people may also have a few friends with
      quite different opinions. To model this situation, we propose a bounded
      confidence plus random selection model, in which each agent has several long
      range neighbors outside the bound who are selected according to a similarity
      based probability rule. We find that the opinions of all agents can reach a
      consensus in bounded time. We further consider the situation when agents ignore
      the bound of confidence and select all their neighbors randomly according to the
      similarity-based probability rule. We prove that in this scenario the whole group
      could also reach a consensus but in the probability sense. 

PMID- 24132249
TI  - Topiramate for the treatment of cocaine addiction: a randomized clinical trial.
AB  - IMPORTANCE: No medication has been established as an efficacious treatment for
      cocaine dependence. We hypothesized that dual modulation of the mesocorticolimbic
      dopamine system by topiramate-a glutamate receptor antagonist and gamma
      aminobutyric acid receptor agonist-would result in efficacious treatment for
      cocaine dependence compared with placebo. OBJECTIVE: To determine the efficacy of
      topiramate vs placebo as a treatment for cocaine dependence. DESIGN, SETTING, AND
      PARTICIPANTS: Double-blind, randomized, placebo-controlled, 12-week trial of 142
      cocaine-dependent adults in clinical research facilities at the University of
      Virginia between November 22, 2005, and July 25, 2011. INTERVENTIONS: Topiramate
      (n = 71) or placebo (n = 71) in escalating doses from 50 mg/d to the target
      maintenance dose of 300 mg/d in weeks 6 to 12, combined with weekly cognitive
      behavioral treatment. MAIN OUTCOMES AND MEASURES: For the efficacy period, weeks
      6 to 12, the primary outcome was the weekly difference from baseline in the
      proportion of cocaine nonuse days; the secondary outcome was urinary cocaine-free
      weeks, and exploratory outcomes included craving and self- and observer-rated
      global functioning on the Clinical Global Impression scales. RESULTS: Using an
      intent-to-treat analysis, topiramate was more efficacious than placebo at
      increasing the weekly proportion of cocaine nonuse days, irrespective of whether
      missing data were not or were imputed conservatively to the baseline value (13.3%
      vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs
      3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04,
      respectively). Topiramate also was associated, significantly more than placebo,
      with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds
      ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and
      improving observer-rated global functioning (all P < .05). CONCLUSIONS AND
      RELEVANCE: Topiramate is more efficacious than placebo at increasing the mean
      weekly proportion of cocaine nonuse days and associated measures of clinical
      improvement among cocaine-dependent individuals.

PMID- 24132251
TI  - Three dimensional quantitative characterization of magnetite nanoparticles
      embedded in mesoporous silicon: local curvature, demagnetizing factors and
      magnetic Monte Carlo simulations.
AB  - Magnetite nanoparticles embedded within the pores of a mesoporous silicon
      template have been characterized using electron tomography. Linear least squares
      optimization was used to fit an arbitrary ellipsoid to each segmented particle
      from the three dimensional reconstruction. It was then possible to calculate the
      demagnetizing factors and the direction of the shape anisotropy easy axis for
      every particle. The demagnetizing factors, along with the knowledge of spatial
      and volume distribution of the superparamagnetic nanoparticles, were used as a
      model for magnetic Monte Carlo simulations, yielding zero field cooling/field
      cooling and magnetic hysteresis curves, which were compared to the measured ones.
      Additionally, the local curvature of the magnetite particles' docking site within
      the mesoporous silicon's surface was obtained in two different ways and a
      comparison will be given. A new iterative semi-automatic image alignment program
      was written and the importance of image segmentation for a truly objective
      analysis is also addressed. 

PMID- 24132252
TI  - Time for global statistics we can count on.

PMID- 24132264
TI  - NIH campus endures slow decay.

PMID- 24132265
TI  - Modellers react to chemistry award.

PMID- 24132267
TI  - ITER keeps eye on prize.

PMID- 24132266
TI  - Study aims to put IPCC under a lens.

PMID- 24132268
TI  - UK push to open up patients' data.

PMID- 24132269
TI  - Regulators weigh benefits of 'three-parent' fertilization.

PMID- 24132271
TI  - Research evaluation: Impact.

PMID- 24132272
TI  - Research assessments: Judgement day.

PMID- 24132273
TI  - Science publishing: The golden club.

PMID- 24132278
TI  - Communication: Metaphors advance scientific research.

PMID- 24132279
TI  - Publications: No bias behind pollinator research.

PMID- 24132280
TI  - Biodiversity: Safeguard species in warming flatlands.

PMID- 24132281
TI  - Research: Keep PubMed running at all costs.

PMID- 24132282
TI  - Ecology: Genetic engineering in conservation.

PMID- 24132283
TI  - David Barker (1938-2013).

PMID- 24132284
TI  - Genomics: Comparisons across cancers.

PMID- 24132285
TI  - Physical chemistry: Combs for molecules.

PMID- 24132286
TI  - Astrophysics: Super-luminous supernovae on the rise.

PMID- 24132287
TI  - Materials science: To bind or not to bind.

PMID- 24132288
TI  - Criteria for the use of omics-based predictors in clinical trials.
AB  - The US National Cancer Institute (NCI), in collaboration with scientists
      representing multiple areas of expertise relevant to 'omics'-based test
      development, has developed a checklist of criteria that can be used to determine
      the readiness of omics-based tests for guiding patient care in clinical trials.
      The checklist criteria cover issues relating to specimens, assays, mathematical
      modelling, clinical trial design, and ethical, legal and regulatory aspects.
      Funding bodies and journals are encouraged to consider the checklist, which they
      may find useful for assessing study quality and evidence strength. The checklist
      will be used to evaluate proposals for NCI-sponsored clinical trials in which
      omics tests will be used to guide therapy. 

PMID- 24132289
TI  - Olivine crystals align during diffusion creep of Earth's upper mantle.
AB  - The crystallographic preferred orientation (CPO) of olivine produced during
      dislocation creep is considered to be the primary cause of elastic anisotropy in
      Earth's upper mantle and is often used to determine the direction of mantle flow.
      A fundamental question remains, however, as to whether the alignment of olivine
      crystals is uniquely produced by dislocation creep. Here we report the
      development of CPO in iron-free olivine (that is, forsterite) during diffusion
      creep; the intensity and pattern of CPO depend on temperature and the presence of
      melt, which control the appearance of crystallographic planes on grain
      boundaries. Grain boundary sliding on these crystallography-controlled boundaries
      accommodated by diffusion contributes to grain rotation, resulting in a CPO. We
      show that strong radial anisotropy is anticipated at temperatures corresponding
      to depths where melting initiates to depths where strongly anisotropic and low
      seismic velocities are detected. Conversely, weak anisotropy is anticipated at
      temperatures corresponding to depths where almost isotropic mantle is found. We
      propose diffusion creep to be the primary means of mantle flow. 

PMID- 24132290
TI  - Mutational landscape and significance across 12 major cancer types.
AB  - The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis
      methods to identify somatic variants across thousands of tumours. Here we present
      data and analytical results for point mutations and small insertions/deletions
      from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort.
      We illustrate the distributions of mutation frequencies, types and contexts
      across tumour types, and establish their links to tissues of origin,
      environmental/carcinogen influences, and DNA repair defects. Using the integrated
      data sets, we identified 127 significantly mutated genes from well-known (for
      example, mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase,
      Wnt/beta-catenin and receptor tyrosine kinase signalling pathways, and cell cycle
      control) and emerging (for example, histone, histone modification, splicing,
      metabolism and proteolysis) cellular processes in cancer. The average number of
      mutations in these significantly mutated genes varies across tumour types; most
      tumours have two to six, indicating that the number of driver mutations required
      during oncogenesis is relatively small. Mutations in transcriptional
      factors/regulators show tissue specificity, whereas histone modifiers are often
      mutated across several cancer types. Clinical association analysis identifies
      genes having a significant effect on survival, and investigations of mutations
      with respect to clonal/subclonal architecture delineate their temporal orders
      during tumorigenesis. Taken together, these results lay the groundwork for
      developing new diagnostics and individualizing cancer treatment. 

PMID- 24132291
TI  - Slowly fading super-luminous supernovae that are not pair-instability explosions.
AB  - Super-luminous supernovae that radiate more than 10(44) ergs per second at their
      peak luminosity have recently been discovered in faint galaxies at redshifts of
      0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae.
      Such models involve stars with original masses 140-260 times that of the Sun that
      now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons
      that prevent gravitational collapse are converted to electron-positron pairs,
      causing rapid contraction and thermonuclear explosions. Many solar masses of
      (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright
      light curves. Such massive progenitors are expected to have formed from metal
      poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at
      redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one
      third that of the Sun was observed to look like a fading pair-instability
      supernova. Here we report observations of two slow-to-fade super-luminous
      supernovae that show relatively fast rise times and blue colours, which are
      incompatible with pair-instability models. Their late-time light-curve and
      spectral similarities to supernova 2007bi call the nature of that event into
      question. Our early spectra closely resemble typical fast-declining super
      luminous supernovae, which are not powered by radioactivity. Modelling our
      observations with 10-16 solar masses of magnetar-energized ejecta demonstrates
      the possibility of a common explosion mechanism. The lack of unambiguous nearby
      pair-instability events suggests that their local rate of occurrence is less than
      6 * 10(-6) times that of the core-collapse rate. 

PMID- 24132292
TI  - Deterministic entanglement of superconducting qubits by parity measurement and
      feedback.
AB  - The stochastic evolution of quantum systems during measurement is arguably the
      most enigmatic feature of quantum mechanics. Measuring a quantum system typically
      steers it towards a classical state, destroying the coherence of an initial
      quantum superposition and the entanglement with other quantum systems.
      Remarkably, the measurement of a shared property between non-interacting quantum
      systems can generate entanglement, starting from an uncorrelated state. Of
      special interest in quantum computing is the parity measurement, which projects
      the state of multiple qubits (quantum bits) to a state with an even or odd number
      of excited qubits. A parity meter must discern the two qubit-excitation parities
      with high fidelity while preserving coherence between same-parity states. Despite
      numerous proposals for atomic, semiconducting and superconducting qubits,
      realizing a parity meter that creates entanglement for both even and odd
      measurement results has remained an outstanding challenge. Here we perform a time
      resolved, continuous parity measurement of two superconducting qubits using the
      cavity in a three-dimensional circuit quantum electrodynamics architecture and
      phase-sensitive parametric amplification. Using postselection, we produce
      entanglement by parity measurement reaching 88 per cent fidelity to the closest
      Bell state. Incorporating the parity meter in a feedback-control loop, we
      transform the entanglement generation from probabilistic to fully deterministic,
      achieving 66 per cent fidelity to a target Bell state on demand. These
      realizations of a parity meter and a feedback-enabled deterministic measurement
      protocol provide key ingredients for active quantum error correction in the solid
      state. 

PMID- 24132293
TI  - Coherent Raman spectro-imaging with laser frequency combs.
AB  - Advances in optical spectroscopy and microscopy have had a profound impact
      throughout the physical, chemical and biological sciences. One example is
      coherent Raman spectroscopy, a versatile technique interrogating vibrational
      transitions in molecules. It offers high spatial resolution and three-dimensional
      sectioning capabilities that make it a label-free tool for the non-destructive
      and chemically selective probing of complex systems. Indeed, single-colour Raman
      bands have been imaged in biological tissue at video rates by using ultra-short
      pulse lasers. However, identifying multiple, and possibly unknown, molecules
      requires broad spectral bandwidth and high resolution. Moderate spectral spans
      combined with high-speed acquisition are now within reach using multichannel
      detection or frequency-swept laser beams. Laser frequency combs are finding
      increasing use for broadband molecular linear absorption spectroscopy. Here we
      show, by exploring their potential for nonlinear spectroscopy, that they can be
      harnessed for coherent anti-Stokes Raman spectroscopy and spectro-imaging. The
      method uses two combs and can simultaneously measure, on the microsecond
      timescale, all spectral elements over a wide bandwidth and with high resolution
      on a single photodetector. Although the overall measurement time in our proof-of
      principle experiments is limited by the waiting times between successive spectral
      acquisitions, this limitation can be overcome with further system development. We
      therefore expect that our approach of using laser frequency combs will not only
      enable new applications for nonlinear microscopy but also benefit other nonlinear
      spectroscopic techniques. 

PMID- 24132294
TI  - Chelicerate neural ground pattern in a Cambrian great appendage arthropod.
AB  - Preservation of neural tissue in early Cambrian arthropods has recently been
      demonstrated, to a degree that segmental structures of the head can be associated
      with individual brain neuromeres. This association provides novel data for
      addressing long-standing controversies about the segmental identities of
      specialized head appendages in fossil taxa. Here we document neuroanatomy in the
      head and trunk of a 'great appendage' arthropod, Alalcomenaeus sp., from the
      Chengjiang biota, southwest China, providing the most complete neuroanatomical
      profile known from a Cambrian animal. Micro-computed tomography reveals a
      configuration of one optic neuropil separate from a protocerebrum contiguous with
      four head ganglia, succeeded by eight contiguous ganglia in an eleven-segment
      trunk. Arrangements of optic neuropils, the brain and ganglia correspond most
      closely to the nervous system of Chelicerata of all extant arthropods, supporting
      the assignment of 'great appendage' arthropods to the chelicerate total group.
      The position of the deutocerebral neuromere aligns with the insertion of the
      great appendage, indicating its deutocerebral innervation and corroborating a
      homology between the 'great appendage' and chelicera indicated by morphological
      similarities. Alalcomenaeus and Fuxianhuia protensa demonstrate that the two main
      configurations of the brain observed in modern arthropods, those of Chelicerata
      and Mandibulata, respectively, had evolved by the early Cambrian. 

PMID- 24132296
TI  - Infectivity of Cryptosporidium andersoni and Cryptosporidium muris to normal and
      immunosuppressive cynomolgus monkeys.
AB  - Cryptosporidium andersoni and Cryptosporidium muris infections have been found in
      the mice and/or cattle. The oocysts of C. andersoni and C. muris have been
      sporadically detected in human feces, but the infectious capacity and features
      have been unknown, because of the scarcity of reports involving human infections.
      To assess the infectivity and the clinical and pathological features of C.
      andersoni and C. muris in primates, an experimental infectious study was
      conducted using cynomolgus monkeys. The monkeys were orally inoculated with
      oocysts of two different C. andersoni Kawatabi types and C. muris RN-66 under
      normal and immunosuppressive conditions. The feces of the monkeys were monitored
      for about 40 days after the administration of oocysts using the flotation method,
      but no shedding oocysts were observed under either both normal or
      immunosuppressive conditions. Gross and histopathological examinations were
      performed on the immunosuppressive monkeys, but these revealed no evidence of
      Cryptosporidium infections, even though the monkeys were subjected to
      immunosuppressive conditions. It is hypothesized that C. andersoni and C. muris
      pose little danger of infection in primates even under immunosuppressive
      conditions.

PMID- 24132297
TI  - Heterogeneity of abnormal prion protein (PrP(Sc)) in murine scrapie prions
      determined by PrP(Sc)-specific monoclonal antibodies.
AB  - In prion diseases, abnormal prion protein (PrP(Sc)) is considered as the main
      component of the infectious agent. Delineation of PrP(Sc) conformation is
      expected to be a critical factor in understanding properties of prions. However,
      practical methods to differentiate between conformers of PrP(Sc) are inadequate.
      Here, we used two PrP(Sc)-specific monoclonal antibodies (mAbs), 3B7 and 3H6, and
      found that mAb 3H6 detected a limited portion of PrP(Sc) in five mice-adapted
      prion strains. The quantity of mAb 3H6-precipitated PrP(Sc) was significantly
      lesser in 22L compared to other strains. This result provides a direct evidence
      of the conformational heterogeneity of PrP(Sc) within the prion strains.
      Conformation-specific probes, like these mAbs, have the potential to be powerful
      tools for investigating conformational variations in PrP(Sc).

PMID- 24132298
TI  - The impact of pulmonary hypertension on morbidity and mortality following major
      lung resection.
AB  - OBJECTIVES: Pulmonary hypertension is considered a poor prognostic factor for or
      even a contraindication to major lung resection, but evidence for this claim is
      lacking. This study evaluates the impact of pulmonary hypertension on morbidity
      and mortality following pulmonary lobectomy. METHODS: Adult patients who
      underwent a lobectomy for cancer and had a transthoracic echocardiogram (TTE)
      performed within the year prior to the operation were included. Pulmonary
      hypertension was defined as an estimated right ventricular systolic pressure
      (RVSP) of >=36 mmHg by TTE. The preoperative characteristics, intraoperative data
      and postoperative outcomes of patients with and those without pulmonary
      hypertension based on TTE were compared. A model for morbidity including
      published risk factors as well as pulmonary hypertension was developed by
      multivariable logistic regression. RESULTS: There were 279 patients without
      pulmonary hypertension and 19 patients with pulmonary hypertension. Patients with
      pulmonary hypertension had a lower preoperative forced expiratory volume in 1 s
      and diffusing capacity of the lung for carbon monoxide than patients without
      pulmonary hypertension and a higher incidence of tricuspid regurgitation and
      mitral regurgitation, but the groups were otherwise similar. The mean RVSP in the
      group of patients with pulmonary hypertension was 47 mmHg. Perioperative
      mortality (0.0 vs 2.9%; P = 1.0) and postoperative complications (57.9 vs 47.7%;
      P = 0.48) were not significantly different between patients with and those
      without pulmonary hypertension. The presence of pulmonary hypertension was not a
      predictor of adverse outcomes in either univariate or multivariate analysis.
      CONCLUSIONS: Lobectomy may be performed safely in selected patients with
      pulmonary hypertension, with complication rates comparable with those experienced
      by patients without pulmonary hypertension.

PMID- 24132299
TI  - A review of 250 ten-year survivors after pneumonectomy for non-small-cell lung
      cancer.
AB  - OBJECTIVES: During the last decades, pneumonectomy has been increasingly seen as
      a risky procedure, first reserved for tumours not amenable to lobectomy, and now
      discouraged even in advanced stages of non-small-cell lung cancer (NSCLC). Our
      purpose was to assess the long-term survival following pneumonectomy for NSCLC
      and its prognostic factors. METHODS: We set a retrospective study including every
      patient who underwent a pneumonectomy for NSCLC in 2 French centres from 1981 to
      2002. We then described the demographic and pathological characteristics of
      patients who survived >10 years, and studied the prognostic factors of long-term
      survival. RESULTS: During the study period, 1466 pneumonectomies were performed
      for NSCLC, including 1121 standard and 345 extended, and accounted for the
      overall population. Postoperative complications occurred in 396 patients (27%),
      including 93 deaths (6.3%). Five- and 10-year survival rates were 32 and 19%,
      respectively. Two-hundred and fifty patients survived >10 years after surgery,
      and accounted for the study group. The study group included a majority of males
      (n = 230, 92%), a mean age of 57 +/- 9.2 years and a majority of clinical stage
      IIIA (n = 117, 46.8%). Induction, right-sided pneumonectomy, extended resection
      and adjuvant therapy were performed in 41 (16.4%), 109 (43.6%), 40 (16%) and 97
      patients (38.8%), respectively. Histology revealed a majority of squamous cell
      carcinoma (n = 181, 72.4%), T2 tumours (n = 117, 36.8%) and N1 disease (n = 105,
      42%). In multivariate analysis, factors associated with adverse outcomes included
      older age, advanced stage, extended resection, non-lethal postoperative
      complication, adenocarcinoma, lymphatic vessel microinvasion, N1 and N2 disease
      and R1 and R2 resection. CONCLUSIONS: During the last 30 years, pneumonectomy was
      effectively performed for advanced NSCLC, allowing a 10-year survival rate of
      19%. Such results have not been reported with other non-surgical treatments and
      confirm that pneumonectomy is still an essential weapon in the armamentarium
      against lung cancer.

PMID- 24132300
TI  - Reply to Tossios et al.

PMID- 24132301
TI  - Homografts for the management of graft infections in the ascending aortic
      position.

PMID- 24132302
TI  - Substitution of gadolinium ethylenediaminetetraacetate with phosphites: towards
      gadolinium deposit in nephrogenic systemic fibrosis.
AB  - In neutral media, reactions of gadolinium ethylenediaminetetraacetates with
      phosphorous acid result in the formation of the mixed-ligand polymeric complex
      K3n[Gd(EDTA)(HPO3)]n.7nH2O () and dimeric complex
      Na6[Gd2(EDTA)2(HPO3)2].2.5NaCl.21H2O () (H4EDTA = ethylenediaminetetraacetic
      acid) in warm solution. Further substitution with citric acid gives the monomeric
      gadolinium citrate with EDTA (NH4)2Na[Gd(EDTA)(H2cit)].4H2O (). The compounds
      were characterized by elemental analysis, single crystal X-ray diffraction, FT
      IR, ESI-MS and thermogravimetric analysis. Structural analysis indicates that
      three coordinated water molecules in the gadolinium ethylenediaminetetraacetate
      trihydrates are replaced by phosphite ions (HPO3(2-)) in the compounds and .
      Gadolinium atoms are octa-coordinated by EDTA and the phosphite ion, the latter
      links adjacent Gd-EDTA units to generate an infinite one-dimensional chain in
      compound and a dimeric octatomic ring in . In complex , coordinated water
      molecules were substituted by the alpha-hydroxy, alpha-carboxy and beta-carboxy
      groups of citrate. Citrate is favourable for inhibiting the formation of Gd-EDTA
      phosphite. All the complexes are very easily soluble in water. The solution
      behavior of the isostructural lanthanum complexes was probed with (13)C and (31)P
      NMR spectra in D2O for comparison. ESI-MS analysis and recrystallization proved
      that complexes and dissociate to the monomeric unit of Gd-EDTA and free HPO3(2-)
      in aqueous solution. Substitutions of gadolinium ethylenediaminetetraacetates to
      and are attributed to be the cause of nephrogenic systemic fibrosis in some way. 

PMID- 24132303
TI  - The binding nature of light hydrocarbons on Fe/MOF-74 for gas separation.
AB  - The application of a metal-organic framework (MOF) has expanded into the area of
      heterogeneous catalysis, gas storage and separation, drug delivery, and
      lightweight magnets. Herein, we investigate the nature of olefin and paraffin
      binding on Fe/MOF-74 and identify several factors that determine separation
      efficiency using the first-principles calculations. The calculated binding
      energies and magnetic orderings are in excellent agreement with those observed in
      experiments. While the olefin strongly interacts with Fe atoms through a well
      known pi-complexation, the HOMO - 1(2) of the paraffin weakly interacts with Fe
      atoms without back-donation, facilitating the olefin-paraffin separation
      primarily. However, the mutual gas-gas interactions and magnetic transitions of
      the MOF host also contribute significantly to the total binding energy of each
      gas molecule as much as 2-28% and 6-8%, respectively, emphasizing the necessity
      that these subtle effects must be handled carefully when considering selective
      binding with small energy differences. In particular, Fe/MOF-74 is shown to be a
      unique system where the guest-dependent magnetic transition observed only for the
      olefin adsorption is a secondary reason for the high olefin-paraffin adsorption
      selectivity measured. The understanding of the hydrocarbon binding energetics can
      provide a way to modify MOFs for enhanced separation/sorption properties that can
      be complemented by principles of kinetic separation. 

PMID- 24132305
TI  - Inhibition of the family 20 glycoside hydrolase catalytic modules in the
      Streptococcus pneumoniae exo-beta-D-N-acetylglucosaminidase, StrH.
AB  - Streptococcus pneumoniae produces a cell-surface attached beta-N
      acetylglucosaminidase called StrH that is used by this pathogen to process the
      termini of host complex N-linked glycans. N-Acetyl-D-glucosamine-thiazoline (NAG
      Thiazoline, NGT) and O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl
      carbamate (PUGNAc) are inhibitors of the two family 20 glycoside hydrolase
      catalytic modules within StrH and these inhibitors have proven useful in
      modulating the activity of StrH in assays that model aspects of the host
      bacterium interaction. Here we explore the molecular basis of StrH inhibition
      through structural, kinetic, thermodynamic and site-directed mutagenic analyses
      using the recombinantly produced independent catalytic modules of StrH (GH20A and
      GH20B) and the inhibitors NGT and PUGNAc. The results reveal a similar binding
      mode of the sugar moiety of these inhibitors at the -1 subsite in the active
      sites of GH20A and GH20B. The lower affinity of NGT as compared to PUGNAc for
      these catalytic modules can be attributed to the hydrophobic phenylcarbamate
      moiety of PUGNAc that is absent in NGT. This moiety also displayed variations in
      its interactions with the active sites of GH20A and GH20B that provide a
      rationale for the 400-fold difference observed in the Ki values of this compound
      for these two beta-N-acetylglucosaminidase catalytic modules.

PMID- 24132306
TI  - Relying on what they know: older Slavic emigres managing chronic health
      conditions.
AB  - As the U.S. population ages and becomes increasingly diverse, health care
      professionals need to recognize the role of culture and life course in managing
      chronic health conditions. Older emigres, in particular, face daunting challenges
      learning to navigate a new language, country, and health care system. In this
      focused ethnography, data collection included 16 months of participant
      observation and interviews with 28 Slavic participants (older emigres, family
      caregivers, and key informants). Participants shared beliefs about the causes of
      chronic conditions, described treatments used, identified barriers to care, and
      expressed their expectations of U.S. health care providers. The findings provide
      insight into older emigres' explanatory models of health, which can be used by
      health care providers to improve health care delivery to this underserved
      population. 

PMID- 24132307
TI  - A new sphenodontian (Lepidosauria: Rhynchocephalia) from the Late Triassic of
      Argentina and the early origin of the herbivore opisthodontians.
AB  - Sphenodontians were a successful group of rhynchocephalian reptiles that
      dominated the fossil record of Lepidosauria during the Triassic and Jurassic.
      Although evidence of extinction is seen at the end of the Laurasian Early
      Cretaceous, they appeared to remain numerically abundant in South America until
      the end of the period. Most of the known Late Cretaceous record in South America
      is composed of opisthodontians, the herbivorous branch of Sphenodontia, whose
      oldest members were until recently reported to be from the Kimmeridgian-Tithonian
      (Late Jurassic). Here, we report a new sphenodontian, Sphenotitan leyesi gen. et
      sp. nov., collected from the Upper Triassic Quebrada del Barro Formation of
      northwestern Argentina. Phylogenetic analysis identifies Sphenotitan as a basal
      member of Opisthodontia, extending the known record of opisthodontians and the
      origin of herbivory in this group by 50 Myr. 

PMID- 24132308
TI  - Sperm competition risk generates phenotypic plasticity in ovum fertilizability.
AB  - Theory predicts that sperm competition will generate sexual conflict that favours
      increased ovum defences against polyspermy. A recent study on house mice has
      shown that ovum resistance to fertilization coevolves in response to increased
      sperm fertilizing capacity. However, the capacity for the female gamete to adjust
      its fertilizability as a strategic response to sperm competition risk has never,
      to our knowledge, been studied. We sourced house mice (Mus domesticus) from
      natural populations that differ in the level of sperm competition and sperm
      fertilizing capacity, and manipulated the social experience of females during
      their sexual development to simulate conditions of either a future 'risk' or 'no
      risk' of sperm competition. Consistent with coevolutionary predictions, we found
      lower fertilization rates in ova produced by females from a high sperm
      competition population compared with ova from a low sperm competition population,
      indicating that these populations are divergent in the fertilizability of their
      ova. More importantly, females exposed to a 'risk' of sperm competition produced
      ova that had greater resistance to fertilization than ova produced by females
      reared in an environment with 'no risk'. Consequently, we show that variation in
      sperm competition risk during development generates phenotypic plasticity in ova
      fertilizability, which allows females to prepare for prevailing conditions during
      their reproductive life. 

PMID- 24132309
TI  - Evolution of growth by genetic accommodation in Icelandic freshwater stickleback.
AB  - Classical Darwinian adaptation to a change in environment can ensue when
      selection favours beneficial genetic variation. How plastic trait responses to
      new conditions affect this process depends on how plasticity reveals to selection
      the influence of genotype on phenotype. Genetic accommodation theory predicts
      that evolutionary rate may sharply increase when a new environment induces
      plastic responses and selects on sufficient genetic variation in those responses
      to produce an immediate evolutionary response, but natural examples are rare. In
      Iceland, marine threespine stickleback that have colonized freshwater habitats
      have evolved more rapid individual growth. Heritable variation in growth is
      greater for marine full-siblings reared at low versus high salinity, and genetic
      variation exists in plastic growth responses to low salinity. In fish from
      recently founded freshwater populations reared at low salinity, the plastic
      response was strongly correlated with growth. Plasticity and growth were not
      correlated in full-siblings reared at high salinity nor in marine fish at either
      salinity. In well-adapted lake populations, rapid growth evolved jointly with
      stronger plastic responses to low salinity and the persistence of strong plastic
      responses indicates that growth is not genetically assimilated. Thus, beneficial
      plastic growth responses to low salinity have both guided and evolved along with
      rapid growth as stickleback adapted to freshwater. 

PMID- 24132310
TI  - Functional morphology and biomechanics of branch-stem junctions in columnar
      cacti.
AB  - Branching in columnar cacti features morphological and anatomical characteristics
      specific to the subfamily Cactoideae. The most conspicuous features are the
      pronounced constrictions at the branch-stem junctions, which are also present in
      the lignified vascular structures within the succulent cortex. Based on finite
      element analyses of ramification models, we demonstrate that these indentations
      in the region of high flexural and torsional stresses are not regions of
      structural weakness (e.g. allowing vegetative propagation). On the contrary, they
      can be regarded as anatomical adaptations to increase the stability by fine
      tuning the stress state and stress directions in the junction along prevalent
      fibre directions. Biomimetic adaptations improving the functionality of
      ramifications in technical components, inspired, in particular, by the fine-tuned
      geometrical shape and arrangement of lignified strengthening tissues of
      biological role models, might contribute to the development of alternative
      concepts for branched fibre-reinforced composite structures within a limited
      design space. 

PMID- 24132311
TI  - Evolutionary routes to non-kin cooperative breeding in birds.
AB  - Cooperatively breeding animals live in social groups in which some individuals
      help to raise the offspring of others, often at the expense of their own
      reproduction. Kin selection--when individuals increase their inclusive fitness by
      aiding genetic relatives--is a powerful explanation for the evolution of
      cooperative breeding, particularly because most groups consist of family members.
      However, recent molecular studies have revealed that many cooperative groups also
      contain unrelated immigrants, and the processes responsible for the formation and
      maintenance of non-kin coalitions are receiving increasing attention. Here, I
      provide the first systematic review of group structure for all 213 species of
      cooperatively breeding birds for which data are available. Although the majority
      of species (55%) nest in nuclear family groups, cooperative breeding by unrelated
      individuals is more common than previously recognized: 30% nest in mixed groups
      of relatives and non-relatives, and 15% nest primarily with non-relatives.
      Obligate cooperative breeders are far more likely to breed with non-kin than are
      facultative cooperators, indicating that when constraints on independent breeding
      are sufficiently severe, the direct benefits of group membership can substitute
      for potential kin-selected benefits. I review three patterns of dispersal that
      give rise to social groups with low genetic relatedness, and I discuss the
      selective pressures that favour the formation of such groups. Although kin
      selection has undoubtedly been crucial to the origin of most avian social
      systems, direct benefits have subsequently come to play a predominant role in
      some societies, allowing cooperation to persist despite low genetic relatedness.

PMID- 24132312
TI  - Sound amplification by means of a horn-like roosting structure in Spix's disc
      winged bat.
AB  - While sound is a signal modality widely used by many animals, it is very
      susceptible to attenuation, hampering effective long-distance communication. A
      strategy to minimize sound attenuation that has been historically used by humans
      is to use acoustic horns; to date, no other animal is known to use a similar
      structure to increase sound intensity. Here, we describe how the use of a
      roosting structure that resembles an acoustic horn (the tapered tubes that form
      when new leaves of plants such as Heliconia or Calathea species start to unfurl)
      increases sound amplification of the incoming and outgoing social calls used by
      Spix's disc-winged bat (Thyroptera tricolor) to locate roosts and group members.
      Our results indicate that incoming calls are significantly amplified as a result
      of sound waves being increasingly compressed as they move into the narrow end of
      the leaf. Outgoing calls were faintly amplified, probably as a result of
      increased sound directionality. Both types of call, however, experienced
      significant sound distortion, which might explain the patterns of signal
      recognition previously observed in behavioural experiments. Our study provides
      the first evidence of the potential role that a roost can play in facilitating
      acoustic communication in bats. 

PMID- 24132316
TI  - Bartholomew the apostle: the saint of dermatology.

PMID- 24132317
TI  - Dermatology on a high note.

PMID- 24132318
TI  - What's in a name?: Hailey-Hailey disease.

PMID- 24132319
TI  - Bechet vs Behcet: the name is not the same.

PMID- 24132320
TI  - Efficacy of topical antifungal agents in the treatment of dermatophytosis: an
      incomplete meta-analysis.

PMID- 24132321
TI  - Neutrophilic urticaria with systemic inflammation identical to neutrophilic
      urticarial dermatosis.

PMID- 24132322
TI  - Efficacy of topical antifungal agents in the treatment of dermatophytosis--reply.

PMID- 24132323
TI  - The importance of a name.

PMID- 24132324
TI  - In myofibroblastic sarcomas of the head and neck, mitotic activity and necrosis
      define grade: a case study and literature review.
AB  - Low-grade myofibroblastic sarcoma (LGMFS) is considered a distinct entity in the
      World Health Organization classification of soft tissue neoplasms, defined as an
      atypical myofibroblastic proliferation with fibromatosis-like features and a
      predilection for the head and neck. A substantial subset of previously reported
      myofibroblastic sarcomas (MFS), particularly in the head and neck region, are
      associated with appreciable tumor-associated morbidity and mortality and should
      be differentiated from the more indolent LGMFS. However, no specific
      morphological criteria have been developed to define the entity of LGMFS. We have
      reviewed histological findings in conjunction with clinical follow-up information
      of previously reported MFS in the head and neck region in the English literature,
      with the addition of five new cases from our institution. We found that MFSs with
      6 or more mitoses per 10 high power fields and/or presence of spontaneous
      necrosis were accompanied by a higher mortality rate that is statistically
      significant.

PMID- 24132325
TI  - Photoluminescence via gap plasmons between single silver nanowires and a thin
      gold film.
AB  - In this work, we investigate the one-photon photoluminescence from a system
      consisting of an Ag nanowire on an Au film with a ~6 nm dielectric spacer that
      supports a localized resonance known as the gap plasmon mode. Although the Ag
      nanowire and Au film exhibit weak photoluminescence on their own, the combined
      system produces an enhanced PL emission. Our analysis reveals that the strong PL
      emission in this system was due to the enhanced laser absorption in, and PL
      emission from Au, with the Ag nanowire acting as an efficient antenna. The PL due
      to the gap mode is sensitive to the polarization of the laser excitation with
      respect to the nanowire orientation, and shows a clear dipolar emission profile.
      PL emission wavelengths were found to depend only on the nanowire width, and
      independent of its length. These observations were supported by simulation
      results indicating that gap plasmons are excited by light polarized transverse to
      the nanowire length.

PMID- 24132327
TI  - Prehospital anaesthesia performed by physician/critical care paramedic teams in a
      major trauma network in the UK: a 12 month review of practice.
AB  - INTRODUCTION: In the West Midlands region of the UK, delivery of pre-hospital
      care has been remodelled through introduction of a 24 h Medical Emergency
      Response Incident Team (MERIT). Teams including physicians and critical care
      paramedics (CCP) are deployed to incidents on land-based and helicopter-based
      platforms. Clinical practice, including delivery of rapid sequence induction of
      anaesthesia (RSI), is underpinned by standard operating procedures (SOP). This
      study describes the first 12 months experience of prehospital RSI in the MERIT
      scheme in the West Midlands. METHODS: Retrospective review of the MERIT clinical
      database for the 12 months following the launch of the scheme. Data was collected
      relating to the number of RSIs performed; indication for RSI; number of
      intubation attempts; grade of view on laryngoscopy and the base speciality/grade
      of the operator performing intubation. RESULTS: MERIT teams were activated 1619
      times, attending scene in 1029 cases. RSI was performed 142 times (13.80% of
      scene attendances). There was one recorded case of failure to intubate requiring
      insertion of a supraglottic airway device (0.70%). In over a third of RSI cases,
      CCPs performed laryngoscopy and intubation (n=53, 37.32%). Proficiency of
      obtaining Grade I view at laryngoscopy was similar for physicians (74.70%) and
      CCPs (77.36%). Intubation was successful at the first attempt in over 90% of
      cases. CONCLUSIONS: This study demonstrates that operation within a system that
      provides high levels of exposure, underpinned by comprehensive and robust
      training and governance frameworks, promotes levels of performance in successful
      prehospital RSI regardless of base speciality or profession.

PMID- 24132326
TI  - Hymenobacter swuensis sp. nov., a gamma-radiation-resistant bacteria isolated
      from mountain soil.
AB  - Gram stain-negative and non-motile bacteria, designated as DY53(T) and DY43, were
      isolated from mountain soil in South Korea prior exposure with 5 kGy gamma
      radiation. Phylogenetic analysis based on 16S rRNA gene sequence revealed that
      the strains belonged to the family Cytophagaceae in the class Cytophagia. 16S
      rRNA gene sequence similarity of strains DY53(T) and DY43 was 100 %. The highest
      degrees of sequence similarities of strains DY53(T) and DY43 were found with
      Hymenobacter perfusus A1-12(T) (98.8 %), Hymenobacter rigui WPCB131(T) (98.5 %),
      H. yonginensis HMD1010(T) (97.9 %), H. xinjiangensis X2-1g(T) (96.6 %), and H.
      gelipurpurascens Txg1(T) (96.5 %). The DNA G+C content of the novel strains
      DY53(T) and DY43 were 59.5 mol%. Chemotaxonomic data revealed that strains
      possessed major fatty acids such as C15:0 iso, C15:0 anteiso, C16:1 omega5c,
      summed feature 3 (16:1 omega7c/omega6c), summed feature 4 (17:1 anteiso B/iso I)
      and C17:0 iso, and major polar lipid was phosphatidylethanolamine. The novel
      strains showed resistance to gamma radiation, with a D10 value (i.e., the dose
      required to reduce the bacterial population by tenfold) in excess of 5 kGy. Based
      on these data, strains DY53(T) and DY43 should be classified as representing a
      novel species, for which the name Hymenobacter swuensis sp. nov. is proposed,
      with the type strain DY53(T) (=KCTC 32018(T) = JCM 18582(T)) and DY43 (=KCTC
      32010).

PMID- 24132328
TI  - Health in arts: are arts settings better than sports settings for promoting anti
      smoking messages?
AB  - AIM: Tobacco smoking is a leading cause of preventable mortality and morbidity.
      Since 1991, the Western Australian Health Promotion Foundation (Healthway) has
      sponsored the arts and sport in exchange for cigarette smoke-free events, smoke
      free policies and the promotion of anti-smoking messages (e.g. Quit, Smoke Free
      or Smarter than Smoking). As health promoters often look for innovative and
      effective settings to advocate health, and as the approach of sponsoring the arts
      to promote health to the general population is uncommon, the purpose of this
      study was to evaluate the effectiveness of 'health in arts' by measuring the
      cognitive impact (message awareness, comprehension, acceptance and intention) of
      promoting anti-smoking messages at arts events, and comparing findings to sports
      events, a more traditional health promotion setting. METHOD: A secondary analysis
      of the 2004-2009 Healthway Sponsorship Monitor data was conducted. A total of 12
      arts events (n = 592 respondents) and 9 sports events (n = 420 respondents)
      sponsored by Healthway to promote an anti-smoking message were evaluated. The
      study was cross-sectional in design. Participants were residents of Western
      Australia aged 15 years or above and attended events as part of an audience or as
      a spectator. Descriptive and regression analyses were conducted. RESULTS: After
      adjustment for demographic variables, smoking status and clustering, arts events
      were found to be as effective in promoting anti-smoking message awareness,
      comprehension and acceptance and twice as effective on intention to act (p = .03)
      compared with sports events. CONCLUSION: This study provides evidence of the
      effectiveness of arts sponsorship to promote health to the general population,
      that is, health in arts. Promoting an anti-smoking message in arts settings was
      as, or more, effective than in sports settings. Results suggest that the arts
      should be utilised to communicate and reinforce anti-smoking messages to the
      general population. The suitability of the arts to promote other types of health
      messages should be investigated further.

PMID- 24132330
TI  - Chemistry masterclass.

PMID- 24132329
TI  - Genome-wide network analysis of Wnt signaling in three pediatric cancers.
AB  - Genomic structural alteration is common in pediatric cancers, and analysis of
      data generated by the Pediatric Cancer Genome Project reveals such tumor-related
      alterations in many Wnt signaling-associated genes. Most pediatric cancers are
      thought to arise within developing tissues that undergo substantial expansion
      during early organ formation, growth and maturation, and Wnt signaling plays an
      important role in this development. We examined three pediatric tumors
      medullobastoma, early T-cell precursor acute lymphoblastic leukemia, and
      retinoblastoma-that show multiple genomic structural variations within Wnt
      signaling pathways. We mathematically modeled this pathway to investigate the
      effects of cancer-related structural variations on Wnt signaling. Surprisingly,
      we found that an outcome measure of canonical Wnt signaling was consistently
      similar in matched cancer cells and normal cells, even in the context of
      different cancers, different mutations, and different Wnt-related genes. Our
      results suggest that the cancer cells maintain a normal level of Wnt signaling by
      developing multiple mutations.

PMID- 24132331
TI  - Drug discovery: Structure-led design.

PMID- 24132332
TI  - Q&A: A lateral thinker. Interview by Diane Wu.

PMID- 24132333
TI  - Q&A: The technology starter. Interview by Valerie Gerard.

PMID- 24132334
TI  - Q&A: The bond shifter. Interview by Rebecca Melen.

PMID- 24132335
TI  - Q&A: A man of many dimensions. Interview by Stephanie Harris.

PMID- 24132336
TI  - Q&A: A sustainable chemist. Interview by Jonathan Moerdyk.

PMID- 24132337
TI  - Energy: Fuelling the future.

PMID- 24132339
TI  - Design and fabrication of a series of metal-mediated assemblies with
      tetrapyridylporphyrins for supramolecular solar cells.
AB  - In this work, a metal-mediated assembling strategy has been used to organize a
      series of new assemblies based on tetrapyridylporphyrin () on nanostructured TiO2
      electrode surfaces, wherein the metal ions (, = Zn(2+), Cd(2+), Hg(2+) and
      Mn(2+)) bridge the pyridyl units of and (E)-4-[(pyridin-4-ylmethylene)
      amino]benzoic acid (), resulting in a assembled mode. The assembled structures
      were characterized by transmission electron microscopy (TEM), computational
      calculations, energy-dispersive X-ray spectroscopy (EDX), IR, UV-vis absorption
      and fluorescence spectra. The performances of the assembly-sensitized solar cells
      were also measured under an irradiance of 100 mW cm(-2) AM 1.5G sunlight.
      Photoelectrochemical results reveal a relatively large photocurrent of the
      device. Simultaneously, a large open-circuit photovoltage and a significantly
      improved conversion efficiency of the device are also observed. These findings
      may serve as another good testing ground for the fabrication of supramolecular
      solar cells in future. 

PMID- 24132346
TI  - Optical trapping of NaYF4:Er3+,Yb3+ upconverting fluorescent nanoparticles.
AB  - We report on the first experimental observation of stable optical trapping of
      dielectric NaYF4:Er(3+),Yb(3+) upconverting fluorescent nanoparticles (~26 nm in
      diameter) using a continuous wave 980 nm single-beam laser. The laser serves both
      to optically trap and to excite visible luminescence from the nanoparticles.
      Sequential loading of individual nanoparticles into the trap is observed from the
      analysis of the emitted luminescence. We demonstrate that the trapping strength
      and the number of individual nanoparticles trapped are dictated by both the laser
      power and nanoparticle density. The possible contribution of thermal effects has
      been investigated by performing trapping experiment in both heavy water and into
      distilled water. For the case of heavy water, thermal gradients are negligible
      and optical forces dominate the trap loading behaviour. The results provide a
      promising path towards real three dimensional manipulation of single
      NaYF4:Er(3+),Yb(3+) nanoparticles for precise fluorescence sensing in
      biophotonics experiments.

PMID- 24132347
TI  - Measuring daily fatigue using a brief scale adapted from the Patient-Reported
      Outcomes Measurement Information System (PROMIS (r)).
AB  - PURPOSE: Daily assessments can provide insight into the temporal characteristics
      of fatigue. They can demonstrate consistency or reveal variability, as when
      fatigue changes with the underlying medical condition, improves with therapy, or
      worsens as a medication side effect. We adapted a fatigue measure from the
      Patient-Reported Outcomes Measurement Information System (PROMIS((r))) for daily
      assessment and examined its psychometric properties in a month-long prospective
      study. METHODS: Three groups of 100 participants each were drawn from two fatigue
      related clinical disorders [osteoarthritis (OA) and premenstrual
      syndrome/premenstrual dysphoric disorder (PMS/PMDD)], and a general population
      sample (GP). They completed brief daily web-based fatigue measures at home on 28
      consecutive evenings. RESULTS: Compliance was high for all samples, based on the
      percent of participants who remained in the study (98 % for GP and OA, 95 % for
      PMS/PMDD). The new scale performed consistently across the groups, sensitively
      measuring fatigue with high reliability (>0.90) especially in the average to high
      fatigue level range. Supporting known-groups validity, fatigue scores were
      elevated in the clinical groups as compared to the GP. The scale was sensitive to
      change, with the PMS/PMDD sample showing a linear increase in fatigue prior to
      menses onset, and a sharp drop off afterward. CONCLUSIONS: The scale was
      psychometrically sound across diverse clinical and general population samples,
      though less reliable when assessing lower levels of fatigue.

PMID- 24132348
TI  - Cancer-specific health-related quality of life in children with brain tumors.
AB  - PURPOSE: To understand the influence of disease and treatment on the health
      related quality of life (HRQOL) of children with brain tumors, compared to the
      HRQOL of children with other cancers, from the viewpoints of children and
      parents. METHODS: A total of 133 children aged 5-18 years and 165 parents of
      children aged 2-18 completed questionnaires of the Pediatric Quality of Life
      Inventory Cancer Module (Pain and Hurt, Nausea, Procedural Anxiety, Treatment
      Anxiety, Worry, Cognitive Problems, Perceived Physical Appearance, and
      Communication scales); higher scores indicate a better HRQOL. The Cancer Module
      scores, weighted by age and treatment status, were compared to those obtained in
      a previous study of children with other cancers (mostly leukemia). RESULTS: The
      weighted mean scores for Pain and Hurt (effect size d = 0.26) and Nausea (d =
      0.23) from child reports and the scores for Nausea (d = 0.28) from parent reports
      were higher for children with brain tumors than scores for children with other
      cancers. The scores for Procedural Anxiety (d = -0.22) and Treatment Anxiety (d =
      -0.32) from parent reports were lower for parents of children with brain tumors
      than the scores for parents of children with other cancers. The child-reported
      Pain and Hurt score of the Cancer Module was higher (d = 0.29) and in less
      agreement (intraclass correlation coefficient = 0.43) with scores from the Brain
      Tumor Module, indicating that assessments completed with the Cancer Module
      misesteem pain and hurt problems in children with brain tumors. CONCLUSIONS: The
      profiles of cancer-specific HRQOL in children with brain tumors differ from those
      of children with other cancers; we therefore suggest that these children receive
      specific psychological support.

PMID- 24132349
TI  - Letter to the Editor: Concerning Paltzer, Jason, Emily Barker, and Whitney P.
      Witt: Measuring the health-related quality of life (HRQoL) of young children in
      resource-limited settings: a review of existing measures, Quality of Life
      Research: Vol. 22, No. 6, August, 2013, pp 1177-1187.

PMID- 24132350
TI  - Investigation of the binding network of IGF-I on the cavity surface of IGFBP4.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) control bioactivity and
      distribution of insulin-like growth factors (IGFs) through high-affinity complex
      of IGFBP and IGF. To get more insight into the binding interaction of IGF system,
      the site-directed mutagenesis and force-driving desorption methods were employed
      to study the interaction mechanism of IGFBP4 and IGF-I by molecular dynamics (MD)
      simulation. In IGF-I, residues Gly7 to Asp12 were found to be the hot spots and
      they mainly anchored on the N-domain of IGFBP4. The contact area, the shape and
      size of protein, the surroundings of the binding site, the hydrophobic and
      electrostatic interaction between the two proteins worked as a complex network to
      regulate the protein-protein interaction. It was also found that the unfolding of
      the helix was not inevitable in the mutant, and it could be regulated by careful
      selection of the substituted amino acid. 

PMID- 24132351
TI  - New insights into the stability of alkenes and alkynes, fluoro-substituted or
      not: a DFT, G4, QTAIM and GVB study.
AB  - Many undergraduate organic chemistry books do not agree with the order of
      relative stability of alkenes towards hydrogenation reactions. Although they
      ascribe the stability of alkenes to the number and spatial position of the alkyl
      groups attached to the vinyl carbon atoms, results from the quantum theory of
      atoms in molecules indicate that the influence of an alkyl substituent on the
      stability of unsaturated hydrocarbons arises from the slight removal of electron
      density of the pi bond, not from donation of their charge density to unsaturated
      carbon atoms as stated in many text books. There is an inverse relation between
      delocalization index--the number of shared electrons between two atoms, or Wiberg
      bond index of C=C bond--and the number of methyl groups attached to the vinyl
      carbon atoms. Electron withdrawing groups (EWGs) attached to unsaturated carbon
      atoms of alkenes and alkynes have two different behaviors: slight EWGs (alkyl
      groups) stabilize unsaturated carbon atoms while the strong EWG destabilizes the
      unsaturated carbon atoms. Generalized valence bond theory was also used to study
      the ambiguous behavior of fluorine substituents bonded to vinyl carbon atoms.

PMID- 24132353
TI  - Management of patients with implanted ventricular assist devices for noncardiac
      surgery: a clinical review.
AB  - While originally primarily used as bridge to cardiac transplantation and bridge
      to recovery, more commonly ventricular assist devices (VADs) are being inserted
      as destination therapy. These patients are being discharged from transplant and
      mechanical assist centers, living as outpatients, and thus the pool of community
      dwelling patients with VADs continues to expand. Not infrequently they present
      for surgical procedures either directly related to the device itself or more
      often incidental to the fact that they have a VAD. This scenario may be more
      common in patients with VADs placed for destination therapy because these
      patients tend to be older and have more comorbidities and are living longer with
      their device. Thus, it is important for all anesthesiologists to be aware of the
      special anesthesia needs of patients with VADs requiring noncardiac surgery. 

PMID- 24132354
TI  - The biomechanical relevance of anterior rotator cuff cable tears in a cadaveric
      shoulder model.
AB  - BACKGROUND: Anterior tears of the supraspinatus tendon are more likely to be
      clinically relevant than posterior tears of the supraspinatus. We hypothesized
      that anterior tears of the supraspinatus tendon involving the rotator cuff cable
      insertion are associated with greater tear gapping, decreased tendon stiffness,
      and increased regional tendon strain under physiologic loading conditions
      compared with equivalently sized tears of the rotator cuff crescent. METHODS:
      Twelve human cadaveric shoulders were randomized to undergo simulation of
      equivalently sized supraspinatus tears of either the anterior rotator cuff cable
      (n = 6) or the adjacent rotator cuff crescent (n = 6). For each specimen, the
      supraspinatus tendon was cyclically loaded from 10 N to 180 N, and a custom three
      dimensional optical system was used to track markers on the surface of the
      tendon. Tear gap distance, stiffness, and regional strains of the supraspinatus
      tendon were calculated. RESULTS: The tear gap distance of large cable tears
      (median gap distance, 5.2 mm) was significantly greater than that of large
      crescent tears (median gap distance, 1.3 mm) (p = 0.002), the stiffness of
      tendons with a small (p = 0.002) or large (p = 0.002) cable tear was
      significantly greater than that of tendons with equivalently sized crescent
      tears, and regional strains across the supraspinatus were significantly increased
      in magnitude and altered in distribution by tears involving the anterior
      insertion of the rotator cuff cable. CONCLUSIONS: These findings support our
      hypothesis that the rotator cuff cable, which is in the most anterior 8 to 12 mm
      of the supraspinatus tendon immediately posterior to the bicipital groove, is the
      primary load-bearing structure within the supraspinatus for force transmission to
      the proximal part of the humerus. Conversely, in the presence of an intact
      rotator cuff cable, the rotator cuff crescent insertion is relatively stress
      shielded and plays a significantly lesser role in supraspinatus force
      transmission. CLINICAL RELEVANCE: Clinicians should consider early repair of
      rotator cuff cable tears, which may need surgical intervention to address their
      biomechanical pathology. In contrast, surgical treatment may be more safely
      delayed for rotator cuff crescent tears.

PMID- 24132355
TI  - Surgical management of pediatric radial neck fractures.
AB  - BACKGROUND: Management of pediatric radial neck fractures is controversial
      regarding acceptable alignment, variable reduction techniques, and suboptimal
      outcomes. The purpose of this study was to assess the characteristics,
      management, and results in a surgical cohort, in efforts to identify prognostic
      factors and offer treatment suggestions. It was hypothesized that less invasive
      reduction maneuvers would precede open reduction and that worse results would
      correlate with fracture severity, open reduction, and the presence of associated
      injuries. METHODS: Retrospective analysis of 151 children in whom a radial neck
      fracture had been surgically treated from 2001 to 2011 was performed. The mean
      age (and standard deviation) and duration of follow-up were 8.4 +/- 2.9 years and
      13.3 +/- 20.0 months, respectively; 40% of the patients were male. A successful
      clinical result was defined as elbow flexion of >=120 degrees , flexion
      contracture of <20 degrees , forearm rotation of >=90 degrees  with >=45 degrees 
      of supination and pronation, and no complications. RESULTS: An isolated radial
      neck fracture occurred in 54% of the children. The mean angulation and
      displacement improved from 43 degrees  +/- 19 degrees  and 37% +/- 35%,
      respectively, before treatment to 13 degrees  +/- 7 degrees  and 0.9% +/- 4%
      after treatment (p < 0.001). Twenty-two procedural combinations were used to
      treat these patients, and 67% of the open reductions were not preceded by
      percutaneous or closed reduction attempts. Among 131 patients with adequate
      follow-up, 31% had an unsuccessful outcome. An age of ten years or more (odds
      ratio [OR] = 5.85, p = 0.001), a time to surgery of two days or less (OR = 4.73,
      p = 0.02), and greater fracture displacement (OR = 1.25 per 10%, p = 0.001) were
      independent predictors of unsuccessful outcomes. Increased fracture severity and
      open reduction were associated with poor results, although the presence of
      concomitant injuries was not. It is predicted that closed manipulation will fail
      for half of fractures angulated >=36 degrees , and that half of fractures
      displaced >=65% will require open reduction. The predicted frequency of
      unsuccessful outcomes is 50% with 76% displacement. CONCLUSIONS: There continues
      to be great variation in the approach to treatment of displaced radial neck
      fractures in children. Suboptimal results occurred in 31% of the patients in this
      series, with worse results in patients older than ten years, who had increased
      fracture severity, and who underwent open reduction. Less invasive reduction
      methods should precede open reduction whenever possible.

PMID- 24132356
TI  - Patient-reported outcomes after total knee replacement vary on the basis of
      preoperative coexisting disease in the lumbar spine and other nonoperatively
      treated joints: the need for a musculoskeletal comorbidity index.
AB  - BACKGROUND: Although the majority of patients report substantial gains in
      physical function following primary total knee replacement, the degree of
      improvement varies widely. To understand the potential role of preoperative pain
      due to other musculoskeletal conditions on postoperative outcomes, we quantified
      bilateral knee and hip pain and low back pain before primary total knee
      replacement and evaluated its association with physical function at six months
      after total knee replacement. METHODS: A prospective cohort of 180 patients
      having primary unilateral total knee replacement reported joint-specific pain in
      right and left hips and knees (Western Ontario and McMaster Universities
      Osteoarthritis Index [WOMAC] pain) as well as the low back (Oswestry Disability
      Index) before surgery. Participants also completed the Short Form-36 (SF-36),
      including the physical and mental component summary scores, before and at six
      months after surgery. RESULTS: Of the 180 patients, 110 (61%) were women; the
      mean age was 65.1 years, the mean body mass index (BMI) was 32.5 kg/m2, and mean
      SF-36 physical component summary score reported before the total knee replacement
      was 33.1. Before total knee replacement, 56.1% of the patients reported no or
      mild pain in the nonoperatively treated knee, hips, and low back. In addition,
      22.2% of the patients had moderate to severe pain in one location; 12.8%, in two
      locations; and 8.9%, in three or four locations. Women reported more moderate to
      severe pain than men did in the nonoperatively treated knee (30% versus 11%; p <
      0.004) and ipsilateral hip (26% versus 11%; p < 0.02). At six months, the mean
      physical component summary score was lower among patients with a greater number
      of preoperative locations of moderate to severe pain. After adjusting for age,
      sex, BMI, and SF-36 mental component summary score, moderate to severe
      preoperative pain in the contralateral knee (p = 0.013), ipsilateral (p = 0.014)
      and contralateral hip (p = 0.026), and low back (p < 0.001) was significantly
      associated with poorer function at six months after total knee replacement.
      CONCLUSIONS: Preoperative musculoskeletal pain in the low back and nonoperatively
      treated lower extremity joints is associated with poorer physical function at six
      months after total knee replacement. The degree of functional improvement varies
      with the burden of musculoskeletal pain in other weight-bearing locations.

PMID- 24132357
TI  - Intraoperative syndesmotic reduction: three-dimensional versus standard
      fluoroscopic imaging.
AB  - BACKGROUND: The quality of reduction of the syndesmosis is an important factor in
      the outcome of ankle fractures associated with a syndesmotic injury. The purpose
      of this study was to directly compare the accuracy of syndesmotic reductions
      obtained using intraoperative standard fluoroscopic techniques against reductions
      obtained using three-dimensional imaging of the Iso-C3D fluoroscope. METHODS: We
      prospectively reviewed imaging studies of patients who were diagnosed as having
      preoperative or intraoperative evidence of syndesmotic diastasis (on the basis of
      the fluoroscopic Cotton test and/or a manual external rotation stress test) who
      underwent syndesmotic fixation at one of two level-I trauma centers. Center A
      used intraoperative computed tomography (CT) imaging to assess reduction (<=2
      mm), while Center B assessed reduction under standard fluoroscopic imaging.
      Postoperative alignment was assessed in a standardized manner, measuring anterior
      fibular distance, posterior fibular distance, and the anterior translation
      distance. Measurements were taken on the injured side and the uninjured side and
      compared between the groups on postoperative axial CT scans. RESULTS: A total of
      thirty-six patients in both centers met our inclusion criteria and were included
      in the data analysis. Despite utilization of the Iso-C(3D), a high rate of
      malreductions was noted in both groups. Anterior translation distance
      malreductions occurred in 31% of the sixteen patients in Center A and 25% of the
      twenty patients in Center B (p = 0.72). The number of anterior fibular distance
      malreductions was similar, with a rate of 38% in Center A and 30% in Center B (p
      = 0.73). A significant difference among the centers (p = 0.03) was noted,
      however, when the posterior fibular distance data was analyzed, with 6% being
      malreduced by >2 mm in Center A and 40% in Center B. CONCLUSIONS: The results of
      our study support previous investigations that have cited high rates of
      syndesmotic malreductions and demonstrate that the addition of advanced
      intraoperative imaging techniques does not help to reduce the rate of
      malreductions in this cohort.

PMID- 24132358
TI  - Outcomes of cementless primary THA for osteonecrosis in HIV-infected patients.
AB  - BACKGROUND: Symptomatic osteonecrosis of the joint is a frequent debilitating
      complication in patients who have been infected with the human immunodeficiency
      virus (HIV). In earlier reports, outcomes of primary total joint arthroplasty in
      such patients have been poor due to early failures, high infection rates, and
      increased complication rates. We report on the clinical and radiographic outcomes
      of primary total hip arthroplasty (THA) in nonhemophilic, HIV-infected patients
      as compared with the outcomes in a cohort of osteonecrosis patients who did not
      have this disease. METHODS: Thirty-four HIV-infected patients (forty-four hips)
      who underwent primary THA for the treatment of osteonecrosis during the period of
      2001 through 2008 were compared with a control cohort of seventy patients
      (seventy-eight hips) who also underwent THA for the treatment of osteonecrosis
      but did not have HIV or other high-risk factors for revision. The patients in the
      HIV study group (eleven women and twenty-three men) had a mean age of forty-eight
      years (range, thirty-four to eighty years) and were followed for a mean of seven
      years (range, four to eleven years). Evaluated outcomes included implant
      survivorship, Harris hip score, infection rate, activity score, postoperative
      Short-Form 36 (SF-36) health survey score, and radiographic outcome. RESULTS:
      Kaplan-Meier survival analysis demonstrated no significant difference in aseptic
      implant survivorship between the HIV and comparison cohorts at the five-year
      (100% vs. 98%, respectively) and ten-year (95% vs. 96.5%, respectively) follow-up
      times. In addition, at the time of final follow-up, the mean postoperative Harris
      hip scores (85 points in the HIV group vs. 87 points in the comparison group),
      activity scores (5.7 points in the HIV group vs. 6.1 points in the comparison
      group), and SF-36 physical (43 points in the HIV group versus 46 points in the
      comparison group) and mental component summary scores (54 points in the HIV group
      versus 57 points in the comparison group) were statistically similar between the
      two cohorts. There were two late infections in the HIV cohort as compared with
      none in the comparison cohort. CONCLUSIONS: Our results demonstrated excellent
      implant survivorship, clinical and radiographic outcomes, and minimal
      complications at the time of midterm follow-up in the HIV-infected patient group.
      We believe that the outcomes associated with primary THA are improving in this
      patient population as a result of better medical management; however, late
      infections are potential complications.

PMID- 24132359
TI  - Ankle bipolar fresh osteochondral allograft survivorship and integration:
      transplanted tissue genetic typing and phenotypic characteristics.
AB  - BACKGROUND: Fresh osteochondral allografts represent a treatment option for early
      ankle posttraumatic arthritis. Transplanted cartilage survivorship, integration,
      and colonization by recipient cells have not been fully investigated. The aim of
      this study was to evaluate the ability of recipient cells to colonize the
      allograft cartilage and to assess allograft cell phenotype. METHODS: Seventeen
      ankle allograft samples were studied. Retrieved allograft cartilage DNA from
      fifteen cases was compared with recipient and donor constitutional DNA by
      genotyping. In addition, gene expression was evaluated on six allograft cartilage
      samples by means of real-time reverse transcription-polymerase chain reaction.
      Histology and immunohistochemistry were performed to support molecular
      observations. RESULTS: Of fifteen genotyped allografts, ten completely matched to
      the host, three matched to the donor, and two showed a mixed profile. Gene
      expression analysis showed that grafted cartilage expressed cartilage-specific
      markers. CONCLUSIONS: The rare persistence of donor cells and the prevailing
      presence of host DNA in retrieved ankle allografts suggest the ingrowth of
      recipient cells into the allograft cartilage, presumably migrating from the
      subchondral bone, in accordance with morphological findings. The expression of
      chondrogenic markers in some of the samples argues for the acquisition of a
      chondrocyte-like phenotype by these cells. CLINICAL RELEVANCE: To our knowledge,
      this is the first report describing the colonization of ankle allograft cartilage
      by host cells showing the acquisition of a chondrocyte-like phenotype.

PMID- 24132360
TI  - Preclinical evaluation of zoledronate to maintain bone allograft and improve
      implant fixation in revision joint replacement.
AB  - BACKGROUND: Revision arthroplasty surgery is often complicated by loss of bone
      stock that can be managed by the use of bone allograft. The allograft provides
      immediate stability for the revision implant but may be resorbed, impairing
      subsequent implant stability. Bisphosphonates can delay allograft resorption. We
      hypothesized that zoledronate-impregnated allograft impacted around revision
      implants would improve implant fixation as characterized by mechanical push-out
      testing and histomorphometry. METHODS: Twenty-four axially pistoning micromotion
      devices were inserted bilaterally into the knees of twelve dogs according to our
      revision protocol. This produced a standardized revision cavity with a loose
      implant, fibrous tissue, and a sclerotic bone rim. Revision surgery was performed
      eight weeks later; after stable titanium revision components were implanted,
      saline solution-soaked allograft was impacted around the component on the control
      side and allograft soaked in 0.005 mg/mL zoledronate was impacted on the
      intervention side. The results were evaluated after four weeks. RESULTS: The
      zoledronate treatment resulted in a 30% increase in ultimate shear strength (p =
      0.023), a 54% increase in apparent shear stiffness (p = 0.002), and a 12%
      increase in total energy absorption (p = 0.444). The quantity of allograft in the
      gap was three times greater in the zoledronate group compared with the control
      group (p < 0.001). The volume fraction of new bone in the zoledronate group (25%;
      95% confidence interval [CI], 22% to 28%) was similar to that in the control
      group (23%; 95% CI, 19% to 26%) (p = 0.311). CONCLUSIONS: The data obtained in
      this canine model suggest that pretreating allograft with zoledronate may be
      beneficial for early stability of grafted revision arthroplasty implants, without
      any adverse effect on bone formation. Clinical studies are warranted. CLINICAL
      RELEVANCE: The zoledronate treatment is simple to apply in the clinical setting.
      The treatment could increase early stability of revision joint replacements
      without impairing new bone formation. In the long term, this can potentially
      improve the longevity of revision joint replacements and reduce the number of
      subsequent revisions.

PMID- 24132361
TI  - Unplanned readmission after total joint arthroplasty: rates, reasons, and risk
      factors.
AB  - BACKGROUND: There has been a major and alarming increase in readmission rates
      following total joint arthroplasty. With proposed changes in reimbursement
      policy, increased rates of unplanned readmission following arthroplasty will
      penalize providers. In particular, it has been proposed that specific
      complications--so-called "zero-tolerance" complications--are unacceptable and
      that their treatment will not qualify for reimbursement. The purpose of this
      study was to identify the incidence, causes, and risk factors for readmission
      following total joint arthroplasty. METHODS: An institutional arthroplasty
      database was utilized to identify those patients undergoing total knee or hip
      arthroplasty from January 2004 through December 2008. A total of 10,633
      admissions for primary arthroplasty (5207 knees and 5426 hips) were identified.
      The same database was used to identify patients requiring an unplanned
      readmission within ninety days of discharge. Multivariate logistic regression was
      utilized to determine the independent predictors of readmission within ninety
      days. RESULTS: There were 591 unplanned readmissions within ninety days of
      discharge following 564 (5.3%) of the 10,633 admissions for total joint
      arthroplasty. The most common cause of readmission was joint-related infection,
      followed by stiffness. Black race, male sex, discharge to inpatient
      rehabilitation, increased duration of hospital stay, unilateral replacement,
      decreased age, decreased distance between home and the hospital, and total knee
      replacement were independent predictors of readmission within ninety days.
      CONCLUSIONS: The high incidence of readmissions secondary to potential "zero
      tolerance" events suggests that these are not easily preventable complications.
      In addition, longer hospitalization and discharge to an inpatient continued-care
      facility increased the risk of readmission.

PMID- 24132362
TI  - Early follow-up of reverse total shoulder arthroplasty in patients sixty years of
      age or younger.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) is an accepted treatment that
      provides reproducible results in the treatment of shoulder arthritis and rotator
      cuff deficiency. Concerns over the longevity of the prosthesis have resulted in
      this procedure being reserved for the elderly. There are limited data in the
      literature with regard to outcomes in younger patients. We report on the early
      outcomes of RSA in a group of patients who were sixty years or younger and who
      were followed for a minimum of two years. METHODS: A retrospective multicenter
      review of sixty-six patients (sixty-seven RSAs) with a mean age of 52.2 years was
      performed. The indications included rotator cuff insufficiency (twenty-nine),
      massive rotator cuff disorder with osteoarthritis (eleven), failed primary
      shoulder arthroplasty (nine), rheumatoid arthritis (six), posttraumatic arthritis
      (four), and other diagnoses (eight). Forty-five shoulders (67%) had at least one
      prior surgical intervention, and thirty-one shoulders (46%) had multiple prior
      surgical procedures. RESULTS: At a mean follow-up time of 36.5 months, mean
      active forward elevation of the arm as measured at the shoulder improved from
      54.6 degrees  to 134.0 degrees  and average active external rotation improved
      from 10.0 degrees  to 19.6 degrees . A total of 81% of patients were either very
      satisfied or satisfied. The mean American Shoulder and Elbow Surgeons (ASES)
      score and visual analog scale (VAS) score for pain improved from 40.0 to 72.4 and
      7.5 to 3.0, respectively. The ability to achieve postoperative forward arm
      elevation of at least 100 degrees  was the only significant predictor of overall
      patient satisfaction (p < 0.05) that was identified in this group. There was a
      15% complication rate postoperatively, and twenty-nine shoulders (43%) had
      evidence of scapular notching at the time of the latest follow-up. CONCLUSIONS:
      RSA as a reconstructive procedure improved function at the time of short-term
      follow-up in our young patients with glenohumeral arthritis and rotator cuff
      deficiency. Objective outcomes in our patient cohort were similar to those in
      previously reported studies. However, overall satisfaction was much lower in this
      patient population (81%) compared with that in the older patient population as
      reported in the literature (90% to 96%).

PMID- 24132363
TI  - What's new in shoulder and elbow surgery.

PMID- 24132364
TI  - Computerized adaptive testing of psychological factors: relation to upper
      extremity disability.
AB  - BACKGROUND: Psychological factors are important mediators of the differences
      between impairment and disability. The most commonly used measures of disability
      and psychological factors are lengthy and are usually administered as paper
      questionnaires. The aim of this study was to assess the correlation between
      perceived disability and psychological factors with use of the user-friendly, web
      based Patient Reported Outcomes Measurement Information System initiative, and to
      compare its correlation with a frequently used, paper-based, pain self-efficacy
      questionnaire. METHODS: A cohort of 213 patients completed a web-based version of
      the abbreviated version of the Disabilities of the Arm, Shoulder and Hand
      questionnaire (QuickDASH), the pain self-efficacy questionnaire, the Patient
      Reported Outcomes Measurement Information System-based computerized adaptive
      testing Pain Interference questionnaire, and the Patient Reported Outcomes
      Measurement Information System-based computerized adaptive testing Depression
      questionnaire. Bivariate and multivariable analyses measured the correlation of
      these psychological measures with QuickDASH. RESULTS: There was large correlation
      between QuickDASH and the Pain Interference computerized adaptive testing (r =
      0.74; p < 0.001), between the Pain Interference computerized adaptive testing and
      the pain self-efficacy questionnaire (r = -0.72; p < 0.001), and between
      QuickDASH and the pain self-efficacy questionnaire (r = -0.76; p < 0.001). The
      Depression computerized adaptive testing showed a medium correlation both with
      QuickDASH (r = 0.37; p < 0.001) and with the Pain Interference computerized
      adaptive testing (r = 0.40; p < 0.001). The best multivariable model for
      QuickDASH included the Pain Interference computerized adaptive testing, prior
      treatment received, and smoking, and accounted for 57% of the variability. Fifty
      one percent of the variability in the QuickDASH was explained by pain
      interference alone. CONCLUSIONS: Maladaptive responses to upper-extremity pain
      are accurately measured by the relatively user-friendly Patient Reported Outcomes
      Measurement Information System-based computerized adaptive testing questionnaire.

PMID- 24132365
TI  - Long-term outcome following carpal wedge osteotomy in the arthrogrypotic patient.
AB  - BACKGROUND: Wrist flexion and ulnar deviation deformity is a common presentation
      in children with amyoplasia congenita. Multiple surgical procedures have been
      reported to correct the deformity to enhance functional independence and improve
      quality of life. We performed a retrospective review to detail our long-term
      results with carpal wedge osteotomy in these patients. METHODS: Medical records
      of all patients with the amyoplasia form of arthrogryposis who underwent carpal
      wedge osteotomy between 1994 and 2008 were reviewed. Patients with a follow-up of
      two years or less were excluded. Preoperative and postoperative resting position
      and range of motion of the wrist were recorded. Interviews and questionnaires
      were completed to assess the mean overall satisfaction level of the parent or
      guardian with the outcome of surgery, function, and task completion with use of
      parent-guardian surveys, the Manual Ability Classification System, and the
      ABILHAND-Kids measure of manual ability. RESULTS: Seventy-five wrists in forty
      six patients who met the inclusion criteria were reviewed. The average age of the
      patients at the time of surgery was 4.3 years (range, nine months to eighteen
      years; median, 2.7 years). The average duration of follow-up was 5.7 years
      (range, two to 10.3 years; median, 5.3 years). The average resting position of
      the wrist postoperatively (11 degrees  of flexion) was significantly different
      from that measured preoperatively (55 degrees  of flexion) (p < 0.001). The arc
      of wrist motion measured preoperatively (32 degrees ) did not differ
      significantly from that measured postoperatively (22 degrees ) (p = 0.4903). The
      location of the motion arc was significantly improved to a more functional
      position. The average active extension of the wrist changed from -37 degrees  of
      extension preoperatively to -11 degrees  of extension postoperatively (p <
      0.001). Active wrist flexion also significantly changed from 69 degrees 
      preoperatively to 33 degrees  postoperatively (p < 0.001). Parent-guardian
      surveys indicated that the mean overall satisfaction score after surgery was 9.1
      of 10 possible points and that the mean ranking for task completion in activities
      of daily living was 4 (easier following surgery). CONCLUSIONS: Long-term outcomes
      reveal that surgical correction of wrist flexion posture in children with
      amyoplasia congenita results in improvement that is sustained over time. The
      surveys and questionnaires completed by parents or guardians indicated that they
      were satisfied with the results of the operation.

PMID- 24132366
TI  - Impact of margin status and local recurrence on soft-tissue sarcoma outcomes.
AB  - BACKGROUND: The impact of local recurrence and surgical resection margin status
      on survival in extremity soft-tissue sarcomas remains to be clearly defined. Our
      aim was to conduct a retrospective analysis of prospectively collected data to
      determine the prognostic relevance of positive resection margins and local
      recurrence for extremity soft-tissue sarcomas for survival. METHODS: Three
      hundred and sixty-three patients who underwent resection of localized primary
      extremity soft-tissue sarcomas with curative intent were selected from the United
      States Department of Defense Automated Central Tumor Registry. Outcomes for local
      recurrence, distant recurrence, disease-specific survival, and overall survival
      were analyzed according to clinical, pathological, and treatment variables with
      use of the Kaplan-Meier method (log-rank test) and the multivariate Cox
      regression model. RESULTS: Positive margins (hazard ratio, 1.99 [95% confidence
      interval, 1.15 to 3.45]), local recurrence (hazard ratio, 2.93 [95% confidence
      interval, 1.38 to 6.23]), and distant recurrence (hazard ratio, 12.13 [95%
      confidence interval, 5.97 to 24.65]) were significantly associated with overall
      survival on multivariate Cox regression analysis. However, for disease-specific
      survival, local recurrence was not significant and tumor size of >10 cm (hazard
      ratio, 2.83 [95% confidence interval, 1.15 to 6.95]), positive margins (hazard
      ratio, 1.95 [95% confidence interval, 1.05 to 3.63]), and distant recurrence
      (hazard ratio, 9.46 [95% confidence interval, 4.37 to 20.47]) were independent
      adverse prognostic factors. The disease-specific survival rate for patients with
      localized soft-tissue sarcomas was 89% (95% confidence interval, 85% to 92%) for
      five years and 75% (95% confidence interval, 70% to 81%) for ten years.
      CONCLUSIONS: Positive surgical margins are consistently associated with adverse
      survival-related outcomes in localized soft-tissue sarcomas of the extremity.
      Local recurrence had a significant impact on overall survival, but not on disease
      specific survival.

PMID- 24132368
TI  - Evidence to support the interpretation and use of the Anatomic Anterior Cruciate
      Ligament Reconstruction Checklist.
AB  - Published papers on anatomic anterior cruciate ligament (ACL) reconstruction
      often lack details in the description of the surgical procedure, and there are
      large variations in anatomic ACL reconstruction techniques. We aimed to develop a
      validated checklist to be used for anatomic ACL reconstruction. First, a list of
      all potential items that could be used in the checklist was generated. Thirty
      four ACL experts were selected to participate in an anonymous online survey to
      rate the importance of these items on a scale of 1 to 4 (with a score of 4 having
      the most importance). The results were verified by surveying a large sample of
      959 orthopaedic specialists who are peer reviewers for four major orthopaedic
      journals. Items were included in the final checklist if they received an
      importance score of 3 or 4 from at least 75% of the survey takers. The survey
      response rate was 79% (twenty-seven of thirty-four) of the ACL experts and 40%
      (379 of 959) of the peer reviewers. The final Anatomic ACL Reconstruction
      Checklist includes seventeen items with a maximum score of 19 points. The final
      checklist underwent preliminary testing for internal consistency, intertester
      reliability, and validity. Cronbach's alpha for internal consistency was 0.82,
      and the intraclass correlation coefficient (ICC) for intertester reliability was
      0.65. This large survey-based study on anatomic ACL reconstruction resulted in
      the development of the Anatomic ACL Reconstruction Checklist; preliminary
      evidence for interpretation of the scores is provided. 

PMID- 24132367
TI  - Lessons learned from selective soft-tissue release for gap balancing in primary
      total knee arthroplasty: an analysis of 1216 consecutive total knee
      arthroplasties: AAOS exhibit selection.
AB  - BACKGROUND: Soft-tissue releases are commonly necessary to achieve symmetrical
      flexion and extension gaps in primary total knee arthroplasty performed with a
      measured resection technique. We reviewed the frequency of required releases
      according to preoperative alignment and the clinical and radiographic results;
      associations with failure, reoperations, and complications are presented.
      METHODS: We reviewed 1216 knees that underwent primary total knee arthroplasty
      from 2004 to 2009; 774 (64%) were in female patients and 442 (36%), in male
      patients. In the coronal plane, 855 knees had preoperative varus deformity, 123
      were neutral, and 238 had valgus deformity. The mean age at the time of the index
      procedure was 62.7 years (range, twenty-three to ninety-four years), and the mean
      body mass index was 32.7 kg/m2 (range, 17.4 to 87.9 kg/m2). Clinical outcomes
      included the Knee Society Score (KSS), implant failure, reoperation, and
      complications. Radiographs were analyzed for component alignment. RESULTS: The
      only difference in the total KSS was found at the time of final follow-up between
      valgus knees with zero releases (total KSS = 178) and those with one or two
      releases (KSS = 160, p = 0.026). Overall, 407 knees (33.5%) required zero
      releases, 686 (56.4%) required one or two releases, and 123 (10.1%) required
      three or more releases. Among varus knees, 37% required zero releases, 55%
      required one or two releases, and 7.5% required three or more releases. Among
      neutral knees, 39% required zero releases, 55% required one or two releases, and
      5.7% required three or more releases. Only 17% of valgus knees required zero
      releases whereas 61% required one or two releases and 21.8% required three or
      more releases. Valgus knees required more releases than neutral or varus knees
      did (p < 0.001). CONCLUSIONS: Selective soft-tissue release for gap balancing in
      primary total knee arthroplasty is an effective technique that produced excellent
      clinical and radiographic results regardless of preoperative alignment.
      Consistent anatomic coronal-plane alignment and soft-tissue balance could be
      achieved without bone cut modification by using measured bone resection and
      selective soft-tissue release.

PMID- 24132369
TI  - Orthopaedic fellowship selection criteria: a survey of fellowship directors.
AB  - BACKGROUND: The pursuit of a fellowship has become increasingly popular over the
      past several years, with >90% of graduating orthopaedic residents applying for a
      fellowship position. Despite the ample literature available pertaining to the
      selection of orthopaedic residents, there is no similar research for the
      selection of fellows. METHODS: Four hundred and fifteen of 475 orthopaedic
      fellowship program directors in the United States were surveyed on selection
      criteria used to choose fellows. The survey asked fellowship directors to rank
      the importance of various criteria on a Likert scale of 1 through 5 points (with
      1 point denoting most important and 5 points denoting least important). RESULTS:
      The overall response rate was 193 (46.5%) of 415 orthopaedic fellowship program
      directors. The most important criteria in selecting an applicant for an interview
      were a letter of recommendation from subspecialty faculty (1.38 points), quality
      of residency program (2.02 points), and a letter of recommendation from the
      residency program director (2.12 points). The most important criteria in
      completing the rank order list following the interview were the interview (1.17
      points), a letter of recommendation from subspecialty faculty (1.46 points), a
      letter of recommendation from the residency program director (2.16 points), and
      expressed interest in program (2.16 points).

PMID- 24132370
TI  - How important is the anterior rotator cuff cable?: commentary on an article by
      Mena M. Mesiha, MD, et al.: "The biomechanical relevance of anterior rotator cuff
      cable tears in a cadaveric shoulder model".

PMID- 24132371
TI  - The controversy continues: commentary on an article by Ryan M. Zimmerman, MD, et
      al.: "Surgical management of pediatric radial neck fractures".

PMID- 24132372
TI  - Amyloid and neurodegeneration: converging and diverging paths.

PMID- 24132373
TI  - Basis for fluctuations in lymphocyte counts in fingolimod-treated patients with
      multiple sclerosis.
AB  - OBJECTIVE: To determine the range of fluctuation in total lymphocyte counts
      (TLCs) in peripheral blood over a 4- to 7-year period in patients with MS
      receiving fingolimod (FTY720) and the relation between TLCs and T-cell subsets
      (CD4+, CD8+, CCR7+/-) that are differentially regulated in the lymph nodes by
      fingolimod. METHODS: TLCs were measured every 3 months in patients (n = 23)
      receiving fingolimod for 4 to 7 years. T-cell subset (CD4+, CD8+, and CCR7+/-)
      analyses were performed on whole-blood samples and/or freshly isolated or
      cryopreserved mononuclear cells. RESULTS: All serially studied patients had mean
      TLCs <0.6 * 10(9) lymphocytes/L. In 30% of patients, 20% to 40% of TLCs were >0.6
      * 10(9) lymphocytes/L vs mean 4.0% for "nonfluctuator" patients. Cross-sectional
      analysis indicated that TLCs of 0.2-0.6 * 10(9) lymphocytes/L correlated with
      numbers of CD8+ effector (CCR7-) cells. For patients discontinuing therapy, TLCs
      between 0.6 and 1.0 * 10(9) lymphocytes/L were associated with a relative
      increase of CD4 T cells and reappearance of CCR7+ (CD4+ and CD8+) T cells.
      Analysis of cryopreserved mononuclear cell samples from patients receiving
      therapy with TLCs >0.6 * 10(9) lymphocytes/L indicated no differences in total
      CD4 or CD8+ T cells but increased proportion of CD4+CCR7+ T cells compared to
      samples with TLCs <0.6 * 10(9) lymphocytes/L. CONCLUSION: Fluctuations of TLCs
      within 0.2-0.6 * 10(9) lymphocytes/L in patients receiving fingolimod reflect
      changes in total CCR7-CD8+ effector cells, a population less regulated by this
      agent. Although less apparent than for patients discontinuing therapy, cells
      expected to be sequestered by this therapy may begin to re-emerge when TLC values
      are >0.6 * 10(9) lymphocytes/L.

PMID- 24132374
TI  - Pulse wave velocity is associated with beta-amyloid deposition in the brains of
      very elderly adults.
AB  - OBJECTIVE: To determine arterial stiffness and beta-amyloid (Abeta) deposition in
      the brain of dementia-free older adults. METHODS: We studied a cohort of 91
      dementia-free participants aged 83-96 years. In 2009, participants completed
      brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid
      plaques in human brain). In 2011, we measured resting blood pressure (BP), mean
      arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in
      the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular
      beds, using a noninvasive and automated waveform analyzer. RESULTS: A total of
      44/91 subjects were Abeta-positive on PET scan. Abeta deposition was associated
      with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2
      fold increase in the odds of being Abeta-positive (p = 0.007). High white matter
      hyperintensity (WMH) burden was associated with increased central PWV, systolic
      BP, and MAP. Compared to Abeta-negative individuals with low WMH burden, each SD
      increase in PWV was associated with a 2-fold to 4-fold increase in the odds of
      being Abeta-positive and having high WMH. CONCLUSIONS: Arterial stiffness was
      associated with Abeta plaque deposition in the brain, independent of BP and APOE
      epsilon4 allele. The associations differed by type of brain abnormality and
      vascular bed measured (e.g., WMH with central stiffness and Abeta deposition and
      mixed stiffness). Arterial stiffness was highest in individuals with both high
      Abeta deposition and WMH, which has been suggested to be a "double hit"
      contributing to the development of symptomatic dementia.

PMID- 24132375
TI  - CSF biomarker changes precede symptom onset of mild cognitive impairment.
AB  - OBJECTIVE: This study evaluated longitudinal CSF biomarker measures collected
      when participants were cognitively normal to determine the magnitude and time
      course of biomarker changes before the onset of clinical symptoms in subjects
      with mild cognitive impairment (MCI). METHODS: Longitudinal CSF collection and
      cognitive assessments were performed on a cohort of 265 participants who were
      cognitively normal at their baseline assessment and subsequently developed MCI or
      dementia. CSF beta-amyloid 1-42 (Abeta1-42), total tau (t-tau), and
      phosphorylated tau (p-tau) were determined longitudinally. Consensus diagnoses
      were completed annually. Cox regression analyses were performed, with baseline
      CSF values and time-dependent rate of change in CSF values as covariates
      (adjusted by baseline age, race, and education), in relation to time to onset of
      mild cognitive symptoms. RESULTS: The mean time from baseline to onset of mild
      cognitive symptoms was 5.41 years. Increased risk of progressing from normal
      cognition to onset of clinical symptoms was associated with baseline values of
      Abeta1-42, p-tau, and the ratios of p-tau/Abeta1-42 and t-tau/Abeta1-42 (p <
      0.002). Additionally, the rate of change in the ratios of t-tau/Abeta1-42 (p <
      0.004) and p-tau/Abeta1-42 (p < 0.02) was greater among participants who were
      subsequently diagnosed with MCI. CONCLUSIONS: Baseline differences in CSF values
      were predictive of clinical symptoms that were a harbinger of a diagnosis of MCI
      more than 5 years before symptom onset, and continue to show longitudinal changes
      as cognitive symptoms develop, demonstrating that baseline and longitudinal
      changes in CSF biomarkers are evident during the preclinical phase of Alzheimer
      disease.

PMID- 24132376
TI  - Isolated acquired primary gusto-lacrimal reflex from a brainstem glioma.

PMID- 24132378
TI  - Amyloid-beta-related angiitis presenting as a uveomeningeal syndrome.
AB  - A 59-year-old man had a 2-month history of nonfluctuating encephalopathy. He
      initially presented acutely with fevers, headaches, and word-finding
      difficulties. The sedimentation rate was elevated with a bland CSF and normal MRI
      head. Body CT showed diffuse pulmonary interstitial thickening with patchy
      opacification. Following treatment for pneumonia, there was resolution of fevers.
      No infectious etiology was identified. Within days of discharge, he developed
      bilateral uveitis, which was successfully treated with corticosteroid eyedrops
      and oral acyclovir. One month later, he developed confusion and unsteadiness.
      Repeat MRI was reportedly normal; body CT showed resolution of lung changes but
      diffuse lymphadenopathy persisted. A lymph node biopsy, reviewed at our
      institution, showed nonspecific reactive changes and fibrosis. Due to progressive
      encephalopathy and worsening headaches 2 months after symptom onset, the patient
      presented to our institution. On examination, he scored 30/38 on the Kokmen short
      test of mental status,(1) losing points for attention and immediate and delayed
      recall. Funduscopy revealed bilateral disc edema. He had mild appendicular ataxia
      and impaired tandem walk. The remainder of the examination was normal. 

PMID- 24132377
TI  - Amyloid-first and neurodegeneration-first profiles characterize incident amyloid
      PET positivity.
AB  - OBJECTIVE: To estimate the incidence of and to characterize cognitive and imaging
      findings associated with incident amyloid PET positivity. METHODS: Cognitively
      normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more
      serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each
      time point, were eligible for analysis (n = 207). Twelve subjects with Alzheimer
      disease dementia were included for comparison. RESULTS: Of the 123 CN
      participants who were amyloid-negative at baseline, 26 met criteria for incident
      amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid
      negative, on average these 26 did not differ on any imaging, demographic, or
      cognitive variables except amyloid PET (by definition) and task-free functional
      connectivity, which at baseline was greater in the incident amyloid-positive
      group. Eleven of the 26 incident amyloid-positive subjects had abnormal
      hippocampal volume, FDG-PET, or both at baseline. CONCLUSIONS: The incidence of
      amyloid PET positivity is approximately 13% per year among CN participants over
      age 70 sampled from a population-based cohort. In 15/26 (58%), incident amyloid
      positivity occurred prior to abnormalities in FDG-PET and hippocampal volume.
      However, 11/26 (42%) incident amyloid-positive subjects had evidence of
      neurodegeneration prior to incident amyloid positivity. These 11 could be
      subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau
      mediated neurodegeneration who newly entered the amyloid pathway. Our findings
      suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile
      pathways to preclinical AD exist.

PMID- 24132379
TI  - Quasi equilibrium, variance effective size and fixation index for populations
      with substructure.
AB  - In this paper, we develop a method for computing the variance effective size N
      eV, the fixation index F ST and the coefficient of gene differentiation G ST of a
      structured population under equilibrium conditions. The subpopulation sizes are
      constant in time, with migration and reproduction schemes that can be chosen with
      great flexibility. Our quasi equilibrium approach is conditional on non-fixation
      of alleles. This is of relevance when migration rates are of a larger order of
      magnitude than the mutation rates, so that new mutations can be ignored before
      equilibrium balance between genetic drift and migration is obtained. The vector
      valued time series of subpopulation allele frequencies is divided into two parts;
      one corresponding to genetic drift of the whole population and one corresponding
      to differences in allele frequencies among subpopulations. We give conditions
      under which the first two moments of the latter, after a simple standardization,
      are well approximated by quantities that can be explicitly calculated. This
      enables us to compute approximations of the quasi equilibrium values of N eV, F
      ST and G ST. Our findings are illustrated for several reproduction and migration
      scenarios, including the island model, stepping stone models and a model where
      one subpopulation acts as a demographic reservoir. We also make detailed
      comparisons with a backward approach based on coalescence probabilities.

PMID- 24132380
TI  - Evolution of dispersal in open advective environments.
AB  - We consider a two-species competition model in a one-dimensional advective
      environment, where individuals are exposed to unidirectional flow. The two
      species follow the same population dynamics but have different random dispersal
      rates and are subject to a net loss of individuals from the habitat at the
      downstream end. In the case of non-advective environments, it is well known that
      lower diffusion rates are favored by selection in spatially varying but
      temporally constant environments, with or without net loss at the boundary. We
      consider several different biological scenarios that give rise to different
      boundary conditions, in particular hostile and "free-flow" conditions. We
      establish the existence of a critical advection speed for the persistence of a
      single species. We derive a formula for the invasion exponent and perform a
      linear stability analysis of the semi-trivial steady state under free-flow
      boundary conditions for constant and linear growth rate. For homogeneous
      advective environments with free-flow boundary conditions, we show that
      populations with higher dispersal rate will always displace populations with
      slower dispersal rate. In contrast, our analysis of a spatially implicit model
      suggest that for hostile boundary conditions, there is a unique dispersal rate
      that is evolutionarily stable. Nevertheless, both scenarios show that
      unidirectional flow can put slow dispersers at a disadvantage and higher
      dispersal rate can evolve. 

PMID- 24132381
TI  - First example of a hexadentate bicyclic phthalocyanine analogue containing a
      divalent metal center.
AB  - A reaction of 1,2-dicyanobenzene and lithium methoxide at 70  degrees C in
      methanol yielded the half-phthalocyanine intermediate, which coordinates to a
      cadmium(II) ion in the subsequent reaction step to give the first example of a
      six-coordinate phthalocyanine analogue containing a divalent metal ion at the
      center.

PMID- 24132382
TI  - Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated
      patients.
AB  - BACKGROUND: Intensive care unit (ICU) patients are exposed to many sources of
      discomfort. Although increasing attention is being given to the detection and
      treatment of pain, very little is given to the detection and treatment of dyspnea
      (defined as "breathing discomfort"). METHODS: Published information on the
      prevalence, mechanisms, and potential negative impacts of dyspnea in mechanically
      ventilated patients are reviewed. The most appropriate tools to detect and
      quantify dyspnea in ICU patients are also assessed. RESULTS/CONCLUSIONS: Growing
      evidence suggests that dyspnea is a frequent issue in mechanically ventilated ICU
      patients, is highly associated with anxiety and pain, and is improved in many
      patients by altering the ventilator settings. CONCLUSIONS: Future studies are
      needed to better delineate the impact of dyspnea in the ICU and to define
      diagnostic, monitoring and therapeutic protocols.

PMID- 24132383
TI  - Outcome of elderly patients with circulatory failure.
AB  - PURPOSE: The proportion of elderly patients admitted to the ICU is increasing.
      Mortality rates are known to increase with age but the impact of age on outcomes
      after circulatory shock has not been well defined. METHODS: We performed a
      secondary analysis of data from a large randomized trial comparing the effects of
      dopamine and norepinephrine on outcome in the ICU. Patients were separated into
      not old (<75 years), old (75-84 years), and very old (>=85 years). RESULTS: Of
      the 1,679 patients included in the initial trial, 1,651 had sufficient age data
      available: 1,157 (70%) were not old, 410 (25%) were old, and 84 (5%) were very
      old. There were minor differences among the age groups in the APACHE II score
      calculated without the age component (not old, 17 +/- 9; old, 18 +/- 9; very old,
      19 +/- 9; p = 0.047), but SOFA scores were similar (not old, 9 +/- 4; old, 9 +/-
      3; very old, 9 +/- 3; p = 0.76). Mortality rates were higher in old and very old
      patients at 28 days, at hospital discharge, and after 6 and 12 months. Most very
      old patients were dead at 6 (92%) and 12 months (97%). Mortality rates increased
      with age in all types of shock. Using multivariable analysis, the risk of death
      was higher in very old patients as compared to not old (adjusted OR 0.33, 95% CI
      0.2-0.56, p < 0.001). CONCLUSIONS: Ageing is independently associated with higher
      mortality rates in patients with circulatory failure, whatever the etiology. By 1
      year after admission, most patients 85 years of age and older were dead.

PMID- 24132384
TI  - Unpredictable combination of metabolic and feeding patterns in malnourished
      critically ill children: the malnutrition-energy assessment question.

PMID- 24132385
TI  - Chemical and biological weapons in the 'new wars'.
AB  - The strategic use of disease and poison in warfare has been subject to a
      longstanding and cross-cultural taboo that condemns the hostile exploitation of
      poisons and disease as the act of a pariah. In short, biological and chemical
      weapons are simply not fair game. The normative opprobrium is, however, not
      fixed, but context dependent and, as a social phenomenon, remains subject to
      erosion by social (or more specifically, antisocial) actors. The cross cultural
      understanding that fighting with poisons and disease is reprehensible, that they
      are taboo, is codified through a web of interconnected measures, principal
      amongst these are the 1925 Geneva Protocol; the Biological Weapons Convention;
      and the Chemical Weapons Convention. Whilst these treaties have weathered the
      storm of international events reasonably well, their continued health is premised
      on their being 'tended to' in the face of contextual changes, particularly facing
      changes in science and technology, as well as the changed nature and character of
      conflict. This article looks at the potential for normative erosion of the norm
      against chemical and biological weapons in the face of these contextual changes
      and the creeping legitimization of chemical and biological weapons.

PMID- 24132386
TI  - Bohn's nodules: peculiar neonatal intraoral lesions mistaken for natal teeth.
AB  - Inclusion cysts of transient nature during the neonatal period are developmental
      lesions, which are seen in the oral cavity of the newborn infant. These lesions
      are classified into three subtypes according to their localizations. When noticed
      by the anxious parents on the gingival surfaces, they are often mistaken for
      natal teeth, which lead to seeking medical attention. Herein, we describe a
      newborn infant with Bohn's nodules to increase the awareness of the physicians to
      this benign, self-limiting lesion.

PMID- 24132389
TI  - Simulation of neutron production using MCNPX+MCUNED.
AB  - In standard MCNPX, the production of neutrons by ions cannot be modelled
      efficiently. The MCUNED patch applied to MCNPX 2.7.0 allows to model the
      production of neutrons by light ions down to energies of a few kiloelectron
      volts. This is crucial for the simulation of neutron reference fields. The
      influence of target properties, such as the diffusion of reactive isotopes into
      the target backing or the effect of energy and angular straggling, can be studied
      efficiently. In this work, MCNPX/MCUNED calculations are compared with results
      obtained with the TARGET code for simulating neutron production. Furthermore,
      MCUNED incorporates more effective variance reduction techniques and a
      coincidence counting tally. This allows the simulation of a TCAP experiment being
      developed at PTB. In this experiment, 14.7-MeV neutrons will be produced by the
      reaction T(d,n)(4)He. The neutron fluence is determined by counting alpha
      particles, independently of the reaction cross section. 

PMID- 24132388
TI  - The association of vitamin D status with cardiometabolic risk factors, obesity
      and puberty in children.
AB  - Low serum 25-hydroxyvitamin D3 (25(OH)D) levels have been associated with insulin
      resistance and cardiovascular diseases. The influences of gender, puberty and
      adiposity on vitamin D status and the relationship between 25(OH)D and
      cardiometabolic risk factors in obese and non-obese children were studied. A
      retrospective analysis was carried out on 168 Turkish children during late
      winter. Age, gender, puberty, body mass index (BMI), 25(OH)D levels and
      cardiometabolic risk factors including lipid profiles, high-sensitivity C
      reactive protein and insulin resistance index calculated by homeostasis model
      assessment (HOMA-IR) were evaluated. The median age of the study population was
      11 (4-16) years, and 102 children (60.7 %) were prepubertal. Overall, 98.2 % of
      patients had 25(OH)D levels lower than 20 ng/mL (median 10.0 (4.0-21.3) ng/mL).
      The 25(OH)D levels did not correlate with BMI. However, an inverse correlation
      was seen between serum 25(OH)D and HOMA-IR (rho = -0.656, p = 0.006) and insulin
      (rho = -0.715, p = 0.002) in pubertal obese subjects. Female gender and puberty
      were all negatively associated with 25(OH)D. CONCLUSION: The association between
      vitamin D status and BMI is complex, and it does not seem to be altered by mild
      obesity. In addition, potential influence of puberty should be kept in mind while
      assessing the relationship between serum 25(OH)D and cardiometabolic risk
      factors.

PMID- 24132387
TI  - Pathological fractures in paediatric patients with inflammatory bowel disease.
AB  - Paediatric inflammatory bowel disease (IBD), especially Crohn's disease (CD), is
      commonly associated with poor skeletal health, related to the direct effects of
      chronic inflammation, prolonged use of glucocorticoid (GC), poor nutrition,
      delayed puberty and low muscle mass. Low bone mineral density is commonly
      reported, although the prevalence of long bone fractures may not be increased in
      these patients. Emerging evidence however suggests that there may be an increased
      risk of vertebral fractures (VFs) in this group. VFs presenting at diagnosis of
      paediatric CD, prior to any GC exposure, have been reported, highlighting the
      deleterious effect of inflammation on skeletal health. This paper reviews the
      published literature on pathophysiology of skeletal morbidity and fractures in
      paediatric IBD, illustrated with a new case report of multiple VFs in a
      prepubertal girl with CD, soon after diagnosis, who received minimal amounts of
      oral GC. Optimising control of disease, addressing vitamin D deficiency,
      encouraging physical activity and ensuring normal growth and pubertal progression
      are paramount to management of bone health in these patients. Despite the lack of
      evidence, there may be a place for bisphosphonate treatment, especially in the
      presence of symptomatic pathological fractures, but this requires close
      monitoring by clinicians with expertise in paediatric bone health. CONCLUSION:
      Chronic inflammation mediated by pro-inflammatory cytokines may have adverse
      effects on skeletal health in paediatric patients with IBD. The risk of vertebral
      fractures may be increased, even without exposure to glucocorticoid. Clinical
      monitoring of these patients requires careful attention to the various factors
      that impact on bone health.

PMID- 24132390
TI  - Monte Carlo tools to supplement experimental microdosimetric spectra.
AB  - Tissue-equivalent proportional counters (TEPCs) are widely used in experimental
      microdosimetry for characterising the radiation quality in radiation protection
      and radiation therapy environments. Generally, TEPCs are filled with tissue
      equivalent gas mixtures, at low gas pressure, to simulate tissue site sizes
      similar to the cell nucleus (1 or 2 um). The TEPC response using Monte Carlo (MC)
      codes can be applied to supplement experimental measurements. Most of general
      purpose MC codes currently available recourse to the condensed-history approach
      to model the electron transport and do not transport low-energy electrons (<1
      keV), which can lead to systematic errors, especially in thin layers and in gas
      condensed medium interfaces. In this work, a comparison between experimental
      microdosimetric spectra of (60)Co and (137)Cs radiation at different simulated
      sizes (from 1.0 to 3.0 MUm) in pure propane versus simulated spectra obtained
      with two general-purpose codes FLUKA and PENELOPE, which include a detailed
      simulation of electron-photon transport in arbitrary materials, including gases,
      is presented. 

PMID- 24132392
TI  - Cloning, expression and characterization of sugarcane (Saccharum officinarum L.)
      transketolase.
AB  - Pentose phosphate pathway (PPP) composed of two functionally-connected phases,
      the oxidative and non-oxidative phase. Both phases catalysed by a series of
      enzymes. Transketolase is one of key enzymes of non-oxidative phase in which
      transfer two carbon units from fructose-6-phosphate to erythrose-4-phosphate and
      convert glyceraldehyde-3-phosphate to xylulose-5-phosphate. In plant, erythrose-4
      phosphate enters the shikimate pathway which is produces many secondary
      metabolites such as aromatic amino acids, flavonoids, lignin. Although
      transketolase in plant system is important, study of this enzyme is still
      limited. Until to date, TKT genes had been isolated only from seven plants
      species, thus, the aim of present study to isolate, study the similarity and
      phylogeny of transketolase from sugarcane. Unlike bacteria, fungal and animal,
      PPP is complete in the cytosol and all enzymes are found cytosolic. However, in
      plant, the oxidative phase found localised in the cytosol but the sub
      localisation for non-oxidative phase might be restricted to plastid. Thus, this
      study was conducted to determine subcellular localization of sugarcane
      transketolase. The isolation of sugarcane TKT was done by reverse transcription
      polymerase chain reaction, followed by cloning into pJET1.2 vector and
      sequencing. This study has isolated 2,327 bp length of sugarcane TKT. The
      molecular phylogenetic tree analysis found that transketolase from sugarcane and
      Zea mays in one group. Classification analysis found that both plants showed
      closer relationship due to both plants in the same taxon i.e. family Poaceae.
      Target P 1.1 and Chloro P predicted that the compartmentation of sugarcane
      transketolase is localised in the chloroplast which is 85 amino acids are plant
      plastid target sequence. This led to conclusion that the PPP is incomplete in the
      cytosol of sugarcane. This study also found that the similarity sequence of
      sugarcane TKT closely related with the taxonomy plants. 

PMID- 24132391
TI  - Interaction of Notch and gp130 signaling in the maintenance of neural stem and
      progenitor cells.
AB  - Notch and gp130 signaling are involved in the regulation of multiple cellular
      processes across various tissues during animal ontogenesis. In the developing
      nervous system, both signaling pathways intervene at many stages to determine
      cell fate-from the first neural lineage commitment and generation of neuronal
      precursors, to the terminal specification of cells as neurons and glia. In most
      cases, the effects of Notch and gp130 signaling in these processes are similar.
      The aim of the current review was to summarize the knowledge regarding the roles
      of Notch and gp130 signaling in the maintenance of neural stem and progenitor
      cells during animal ontogenesis, from early embryo to adult. Recent data show a
      direct crosstalk between these signaling pathways that seems to be specific for a
      particular type of neural progenitors. 

PMID- 24132393
TI  - F99 is critical for dimerization and activation of South African HIV-1 subtype C
      protease.
AB  - HIV-1 protease (PR) is an obligate homodimer which plays a pivotal role in the
      maturation and hence propagation of HIV. Although successful developments on PR
      active site inhibitors have been achieved, the major limiting factor has been the
      emergence of HIV drug-resistant strains. Disruption of the dimer interface serves
      as an alternative mechanism to inactivate the enzyme. The terminal residue, F99,
      was mutated to an alanine to investigate its contribution to dimer stability in
      the South African HIV-1 subtype C (C-SA) PR. The F99A PR and wild-type C-SA PR
      were overexpressed and purified. The activities of the PRs and their ability to
      bind an active site inhibitor, acetyl-pepstatin, were determined in vitro. The
      F99A PR showed no activity and the inability to bind to the inhibitor. Secondary
      and quaternary structure analysis were performed and revealed that the F99A PR is
      monomeric with reduced beta-sheet content. The mutation of F99 to alanine
      disrupted the presumed 'lock-and-key' motif at the terminal dimer interface, in
      turn creating a cavity at the N- and C-terminal antiparallel beta-sheet. These
      findings support the design of inhibitors targeting the C-terminus of the C-SA
      PR, centered on interactions with the bulky F99. 

PMID- 24132396
TI  - Response to patient satisfaction as a possible indicator of quality surgical
      care.

PMID- 24132397
TI  - Valuing patient experience as a unique and intrinsically important aspect of
      health care quality.

PMID- 24132398
TI  - Patient satisfaction as a possible indicator of quality surgical care--reply.

PMID- 24132400
TI  - Investigating photoinduced charge transfer in double- and single-emission PbS@CdS
      core@shell quantum dots.
AB  - We present for the first time detailed investigation of the charge transfer
      behavior of PbS@CdS core@shell quantum dots (QDs) showing either a single
      emission peak from the core or intriguing double emission peaks from the core and
      shell, respectively. A highly non-concentric core@shell structure model was
      proposed to explain the origin of double emissions from monodisperse QDs. Their
      charge transfer behavior was investigated by monitoring photoluminescence (PL)
      intensity variation with the introduction of electron or hole scavengers. It was
      found that the PL quenching of the PbS core is more efficient than that of the
      CdS shell, suggesting more efficient charge transfer from the core to scavengers,
      although the opposite was expected. Further measurements of the PL lifetime
      followed by wave function calculations disclosed that the time scale is the
      critical factor explaining the more efficient charge transfer from the core than
      from the shell. The charge transfer behavior was also examined on a series of
      single-emission core@shell QDs with either different core sizes or different
      shell thicknesses and dominant factors were identified. Towards photovoltaic
      applications, these PbS@CdS QDs were attached onto multi-walled carbon nanotubes
      (MWCNTs) and their charge transfer behavior was compared with that in the PbS
      QD/MWCNT system. Results demonstrate that although the CdS shell serves as an
      electron transfer barrier, the electrons excited in the PbS cores can still be
      transferred into the MWCNTs efficiently when the shell thickness is ~0.7 nm.
      Considering their higher stability, these core@shell QDs are very promising for
      the development of highly efficient QD-based photovoltaic devices. 

PMID- 24132401
TI  - Impact of telavancin on prothrombin time and activated partial thromboplastin
      time as determined using point-of-care coagulometers.
AB  - Telavancin is approved in the United States, Canada, and Europe (At the time of
      submission, the telavancin European marketing authorization for nosocomial
      pneumonia was suspended until Theravance provides evidence of a new European
      Medicines Agency approved supplier) as an antibiotic to treat certain Gram
      positive bacterial skin infections. Telavancin has been shown to prolong
      plasmatic prothrombin (PT) and activated partial thromboplastin (aPTT) clotting
      times in clinical diagnostic lab-based assays. In this study, we evaluated the
      potential for telavancin to prolong whole blood PT/International Normalized Ratio
      (INR) and aPTT tests on point-of-care (POC) instruments. Whole blood collected
      from 8 healthy subjects was supplemented with telavancin to final concentrations
      of 0, 10, 20, and 100 MUg/ml. Final concentrations were selected to match trough,
      twice trough, and peak plasma levels following the approved 10 mg/kg dose. Four
      widely employed POC coagulation instruments were chosen to be representative of
      the POC platforms currently in use.. These systems were the Roche Coaguchek XS,
      the Abbott iSTAT, the ITC Hemochron SIG+, and the Alere INRatio2 POC devices. The
      PT/INR measured by the Coaguchek XS showed the greatest sensitivity to the
      presence of telavancin. The PT/INR measured by the Hemochron SIG+ and iSTAT were
      sensitive to telavancin but to a lesser extent. The INRatio2 was the least
      sensitive to the presence of telavancin when testing the whole blood PT/INR. Only
      the Hemochron SIG+ device was capable of measuring aPTT and showed a
      concentration-dependent increase in aPTT. This study supports the current
      recommendation that PT and aPTT monitoring be conducted immediately to the next
      dose of telavancin when coagulation parameters are tested using POC
      instrumentation. 

PMID- 24132402
TI  - Vascular complications after transcatheter aortic valve implantation (TAVI): risk
      and long-term results.
AB  - Vascular complications are the main safety limitations of transcatheter aortic
      valve implantation (TAVI). The aim of the study was to assess the incidents,
      predictors, and the impact of early vascular complications on prognosis after
      TAVI. This was a single-center analysis of vascular complications related to
      TAVI. Early vascular complications were defined as incidents within 30 days after
      TAVI and comprised complications related to transvascular:
      transfemoral/transsubclavian ,and transapical bioprosthesis implantation.
      Evaluated risk factors were: (1) clinical characteristics, (2) TAVI route, and
      (3) center experience. In patients with transvascular TAVI the impact of: (1)
      diameters of access arteries, vascular sheathes and difference between them, (2)
      arterial wall calcification, and (3) ProStar devices used for access site closure
      were assessed. Arterial wall calcification and arteries diameters were measured
      by 64-slice computer tomography. Arterial wall calcification was graded according
      to 5 degrees  scale. RESULTS: between 2009-2011; follow-up 1-23 months (12 +/-
      15.55), 83 consecutive patients, and 62-91 (81.10 +/- 7.20) years, underwent
      TAVI: 67 (80.72%) patients had transvascular, and 16 (19.27%) patients had
      transapical bioprosthesis implantation. We noted 44 (53.01%) early vascular
      complications: 17 (20.48%) were major and 27 (32.53%) were minor incidents.
      Independent predictors of early vascular complications were: history of anaemia
      (OR 3.497: 95% CI [1.276-9.581]; p = 0.014), diabetes (OR 0.323: 95% CI [0.108
      0.962]; p = 0.042), percutaneous coronary intervention performed as preparation
      for TAVI (OR 4.809: 95 % CI [1.172-19.736]; p = 0.029), and arterial wall
      calcification (OR 1.945: 95% CI [1.063-3.558]; p = 0.03). Of 6 (7.22%) in
      hospital and 10 (12.98%) late deaths: 5 (83.33%) patients and 8 (80%) patients
      respectively had post-procedural vascular complications. Vascular complications,
      which occurred in 30-days after TAVI, predict late mortality (p = 0.036).
      Conclusions derived were: (1) TAVI patients with history of anaemia and diabetes
      required careful monitoring for early vascular complications. (2) If coronary
      intervention before TAVI is required, it should be performed in the time allowing
      vascular injuries to heal. (3) Calcification of access arteries is an independent
      predictor of post-procedural vascular complications; therefore, its estimation
      should be a regular element of preceding computer tomography. (4) Vascular
      complications seem to be predictors of late mortality after TAVI.

PMID- 24132403
TI  - Indication and timing of soft tissue augmentation at maxillary and mandibular
      incisors in orthodontic patients. A systematic review.
AB  - OBJECTIVE: To assess the indication and timing of soft tissue augmentation for
      prevention or treatment of gingival recession when a change in the inclination of
      the incisors is planned during orthodontic treatment. MATERIALS AND METHODS:
      Electronic database searches of literature were performed. The following
      electronic databases with no restrictions were searched: MEDLINE, EMBASE,
      Cochrane, and CENTRAL. Two authors performed data extraction independently using
      data collection forms. RESULTS: No randomized controlled trial was identified.
      Two studies of low-to-moderate level of evidence were included: one of
      prospective and retrospective data collection and one retrospective study. Both
      implemented a periodontal intervention before orthodontics. Thus, best timing of
      soft tissue augmentation could not be assessed. The limited available data from
      these studies appear to suggest that soft tissue augmentation of bucco-lingual
      gingival dimensions before orthodontics may yield satisfactory results with
      respect to the development or progression of gingival recessions. However, the
      strength of the available evidence is not adequate in order to change or suggest
      a possible treatment approach in the daily practice based on solid scientific
      evidence. CONCLUSIONS: Despite the clinical experience that soft tissue
      augmentation of bucco-lingual gingival dimensions before orthodontic treatment
      may be a clinically viable treatment option in patients considered at risk, this
      treatment approach is not based on solid scientific evidence. Moreover, the
      present data do not allow to draw conclusions on the best timing of soft tissue
      augmentation when a change in the inclination of the incisors is planned during
      orthodontic treatment and thus, there is a stringent need for randomized
      controlled trials to clarify these open issues.

PMID- 24132404
TI  - Reliability of four different computerized cephalometric analysis programs: a
      methodological error.

PMID- 24132405
TI  - Reply: To PMID 21502380.

PMID- 24132406
TI  - Transcriptomic analysis of cut tree peony with glucose supply using the RNA-Seq
      technique.
AB  - KEY MESSAGE: Several unigenes encoding ACS and ERF involved in ethylene
      biosynthesis and signal transduction were greatly down-regulated in the petal
      transcriptome of cut tree peony 'Luoyang Hong' with glucose treatment. Glucose
      also repressed stress-related transcription factor genes DREB, CBF, NAC, WRKY and
      bHLH. Tree peony (Paeonia suffruticosa Andrews) is a famous traditional flower in
      China. Glucose supply prolonging vase life of cut tree peony flowers is
      associated with its role in the suppression of sensitivity to ethylene and
      ethylene production, but the regulation mechanism of sugar on ethylene
      biosynthesis and signaling is unclear. In the present work, a normalized cDNA
      pool was constructed as the reference transcriptome from mixed petals of
      different developmental cut tree peony 'Luoyang Hong' and sequenced using the
      Illumina HiSeqTM 2000 platform. We obtained 33,117 unigenes annotated with public
      protein databases. In addition, the transcriptome change in petals of cut tree
      peony with glucose supply and the control treatment was investigated. With non
      redundant annotation, 173 differentially expressed genes were identified, with 41
      up-regulated genes and 132 down-regulated genes. According to RNA-Seq data and
      real-time quantitative polymerase chain reaction validation, one unigene encoding
      ACS, a key ethylene synthetic enzyme, and four unigenes encoding ERF, which is
      involved in ethylene signal transduction was greatly down-regulated with glucose
      treatment. Furthermore, stress-related transcription factor genes DREB, CBF, NAC,
      WRKY and bHLH were also repressed with glucose supply, as well as several other
      stress-responsive and stress-tolerance genes, indicating that glucose supply
      probably releases the effects induced by various environmental stress. All the
      results and analysis are valuable resources for better understanding of the
      beneficial influence of exogenous sugars on cut tree peony.

PMID- 24132409
TI  - Cesarean delivery in a parturient with chronic myeloid leukemia.

PMID- 24132410
TI  - Multimodal imaging of an embolized vena cava filter strut causing right
      ventricular perforation.

PMID- 24132408
TI  - The difficult airway with recommendations for management--part 2--the anticipated
      difficult airway.
AB  - BACKGROUND: Appropriate planning is crucial to avoid morbidity and mortality when
      difficulty is anticipated with airway management. Many guidelines developed by
      national societies have focused on management of difficulty encountered in the
      unconscious patient; however, little guidance appears in the literature on how
      best to approach the patient with an anticipated difficult airway. METHODS: To
      review this and other subjects, the Canadian Airway Focus Group (CAFG) was re
      formed. With representation from anesthesiology, emergency medicine, and critical
      care, CAFG members were assigned topics for review. As literature reviews were
      completed, results were presented and discussed during teleconferences and two
      face-to-face meetings. When appropriate, evidence- or consensus-based
      recommendations were made, and levels of evidence were assigned. PRINCIPAL
      FINDINGS: Previously published predictors of difficult direct laryngoscopy are
      widely known. More recent studies report predictors of difficult face mask
      ventilation, video laryngoscopy, use of a supraglottic device, and
      cricothyrotomy. All are important facets of a complete airway evaluation and must
      be considered when difficulty is anticipated with airway management. Many studies
      now document the increasing patient morbidity that occurs with multiple attempts
      at tracheal intubation. Therefore, when difficulty is anticipated, tracheal
      intubation after induction of general anesthesia should be considered only when
      success with the chosen device(s) can be predicted in a maximum of three
      attempts. Concomitant predicted difficulty using oxygenation by face mask or
      supraglottic device ventilation as a fallback makes an awake approach advisable.
      Contextual issues, such as patient cooperation, availability of additional
      skilled help, and the clinician's experience, must also be considered in deciding
      the appropriate strategy. CONCLUSIONS: With an appropriate airway evaluation and
      consideration of relevant contextual issues, a rational decision can be made on
      whether an awake approach to tracheal intubation will maximize patient safety or
      if airway management can safely proceed after induction of general anesthesia.
      With predicted difficulty, close attention should be paid to details of
      implementing the chosen approach. This should include having a plan in case of
      the failure of tracheal intubation or patient oxygenation.

PMID- 24132407
TI  - The difficult airway with recommendations for management--part 1--difficult
      tracheal intubation encountered in an unconscious/induced patient.
AB  - BACKGROUND: Previously active in the mid-1990s, the Canadian Airway Focus Group
      (CAFG) studied the unanticipated difficult airway and made recommendations on
      management in a 1998 publication. The CAFG has since reconvened to examine more
      recent scientific literature on airway management. The Focus Group's mandate for
      this article was to arrive at updated practice recommendations for management of
      the unconscious/induced patient in whom difficult or failed tracheal intubation
      is encountered. METHODS: Nineteen clinicians with backgrounds in anesthesia,
      emergency medicine, and intensive care joined this iteration of the CAFG. Each
      member was assigned topics and conducted reviews of Medline, EMBASE, and Cochrane
      databases. Results were presented and discussed during multiple teleconferences
      and two face-to-face meetings. When appropriate, evidence- or consensus-based
      recommendations were made together with assigned levels of evidence modelled
      after previously published criteria. CONCLUSIONS: The clinician must be aware of
      the potential for harm to the patient that can occur with multiple attempts at
      tracheal intubation. This likelihood can be minimized by moving early from an
      unsuccessful primary intubation technique to an alternative "Plan B" technique if
      oxygenation by face mask or ventilation using a supraglottic device is non
      problematic. Irrespective of the technique(s) used, failure to achieve successful
      tracheal intubation in a maximum of three attempts defines failed tracheal
      intubation and signals the need to engage an exit strategy. Failure to oxygenate
      by face mask or supraglottic device ventilation occurring in conjunction with
      failed tracheal intubation defines a failed oxygenation, "cannot intubate, cannot
      oxygenate" situation. Cricothyrotomy must then be undertaken without delay,
      although if not already tried, an expedited and concurrent attempt can be made to
      place a supraglottic device.

PMID- 24132411
TI  - Integrating ecological momentary assessment and functional brain imaging methods:
      new avenues for studying and treating tobacco dependence.
AB  - INTRODUCTION: Ecological momentary assessment (EMA) and related methods typically
      entail repeatedly and intensively sampling behavior as it occurs over time and
      under naturalistic conditions. Although the methodological features of EMA make
      it a highly valuable research technique in its own right, EMA can also be a
      potent counterpart to other approaches. One methodological partnership with
      substantial yet largely untapped potential for the study of tobacco dependence is
      the pairing of EMA with functional brain imaging. METHODS: The goal of this
      review is to outline the promise of this approach, with a focus on the combined
      use of EMA and functional magnetic resonance imaging (fMRI). Due to the unique
      and complementary strengths of each method, the merger of EMA and fMRI methods
      has the potential to advance the understanding of tobacco dependence in ways
      difficult or impossible to achieve through the use of either method in isolation.
      RESULTS: In addition to describing a conceptual basis for combining EMA with
      fMRI, we provide a preliminary empirical illustration of this integrative
      approach using data from an ongoing study. CONCLUSIONS: EMA and fMRI have
      independently yielded important findings regarding the nature and treatment of
      tobacco dependence. The integration of these powerful research methods, however,
      holds even greater potential for the field of tobacco research. Additionally,
      recent advances are paving the way for the synergistic use of fMRI and EMA-based
      methods to develop innovative approaches to tobacco cessation.

PMID- 24132412
TI  - Rapid cognitive flexibility of rhesus macaques performing psychophysical task
      switching.
AB  - Three rhesus monkeys (Macaca mulatta) performed a simultaneous chaining task in
      which stimuli had to be sorted according to their visual properties. Each
      stimulus could vary independently along two dimensions (luminosity and radius),
      and a cue indicating which dimension to sort by was random trial to trial. These
      rapid and unpredictable changes constitute a task-switching paradigm, in which
      subjects must encode task demands and shift to whichever task-set is presently
      activated. In contrast to the widely reported task-switching delay observed in
      human studies, our subjects show no appreciable reduction in reaction times
      following a switch in the task requirements. Also, in contrast to the results of
      studies on human subjects, monkeys experienced enduring interference from trial
      irrelevant stimulus features, even after exhaustive training. These results are
      consistent with a small but growing body of evidence that task-switching in
      rhesus macaques differs in basic ways from the pattern of behavior reported in
      studies of human cognition. Given the importance of task-switching paradigms in
      cognitive and clinical assessment, and the frequency with which corresponding
      animal models rely on non-human primates, understanding these differences in
      behavior is essential to the comparative study of cognitive impairment.

PMID- 24132413
TI  - Can orangutans (Pongo abelii) infer tool functionality?
AB  - It is debatable whether apes can reason about the unobservable properties of
      tools. We tested orangutans for this ability with a range of tool tasks that they
      could solve by using observational cues to infer tool functionality. In
      experiment 1, subjects successfully chose an unbroken tool over a broken one when
      each tool's middle section was hidden. This prevented seeing which tool was
      functional but it could be inferred by noting the tools' visible ends that were
      either disjointed (broken tool) or aligned (unbroken tool). We investigated
      whether success in experiment 1 was best explained by inferential reasoning or by
      having a preference per se for a hidden tool with an aligned configuration. We
      conducted a similar task to experiment 1 and included a functional bent tool that
      could be arranged to have the same disjointed configuration as the broken tool.
      The results suggested that subjects had a preference per se for the aligned tool
      by choosing it regardless of whether it was paired with the broken tool or the
      functional bent tool. However, further experiments with the bent tool task
      suggested this preference was a result of additional demands of having to attend
      to and remember the properties of the tools from the beginning of the task. In
      our last experiment, we removed these task demands and found evidence that
      subjects could infer the functionality of a broken tool and an unbroken tool that
      both looked identical at the time of choice.

PMID- 24132414
TI  - Mother knows best: functionally referential alarm calling in white-tailed
      ptarmigan.
AB  - Functionally referential alarm calls have stimulus specificity, distinct acoustic
      structure, and elicit different escape responses that are appropriate to the
      threat. The mechanisms by which escape responses are evoked are not fully
      understood and may range from eliciting innate responses to conveying
      representational information. White-tailed ptarmigan (Lagopus leucurus) are a
      long-lived alpine tundra grouse, which are preyed upon by aerial and terrestrial
      predators. We investigated the hypothesis that alarm calls of ptarmigan hens with
      chicks are functionally referential. We recorded hens' alarm calls in response to
      naturally occurring and model predators in California's Sierra Nevada alpine
      tundra for two summer seasons. We conducted playback experiments in the field to
      determine chick responses to alarm calls. Alarm calls commenced with an extended
      'alerting' note followed by a series of staccato notes grouped into elements.
      Fundamental and dominant frequencies in element notes were significantly higher
      in terrestrial compared to aerial threat alarm calls. Playbacks of terrestrial
      threat alarm calls elicited an upright/alert position by chicks (75 % of
      responses). In response to aerial threat alarm call playbacks, chicks flattened
      to the ground and froze (80 % of responses). To our knowledge, this study
      provides the first empirical evidence of functionally referential alarm calling,
      including the responses of the receivers, in an avian species in the wild.

PMID- 24132415
TI  - Essential methods of plant sample preparation for light microscopy.
AB  - There are various preparatory techniques for light microscopy permitting access
      to the inner structure of plant body and its development. Minute objects might be
      processed as whole-mount preparations, while voluminous ones should be separated
      into smaller pieces. Hereby we summarize some of the "classical" techniques to
      cut more voluminous objects into slices and access their inner structure either
      for simple anatomical analysis or for further processing (e.g., histochemistry,
      immunohistochemistry, in situ hybridization, enzyme histochemistry). 

PMID- 24132416
TI  - Selected simple methods of plant cell wall histochemistry and staining for light
      microscopy.
AB  - Histochemical methods allow for identification and localization of various
      components within the tissue. Such information on the spatial heterogeneity is
      not available with biochemical methods. However, there is limitation of the
      specificity of such detection in context of complex tissue, which is important to
      consider, and interpretations of the results should regard suitable control
      treatments if possible. Hereby we present set of selected simple staining and
      histochemical methods with comments based on our laboratory experience. 

PMID- 24132417
TI  - Resin embedding, sectioning, and immunocytochemical analyses of plant cell walls
      in hard tissues.
AB  - Plant cell walls are structurally diverse macromolecular composites. One of our
      best methodologies to determine the temporal and spatial regulation of cell wall
      polysaccharides in relation to development are monoclonal antibody (MAB) and
      carbohydrate-binding module (CBM) probes and their detection by
      immunofluorescence microscopy. Here we describe resin embedding, sectioning, and
      in situ chemical and enzymatic cell wall disassembly and their use with
      immunocytochemical analyses as a means to unravel the complexity of cell wall
      molecular architecture in hard tissues and seeds. 

PMID- 24132418
TI  - Automated microscopy in forward genetic screening of Arabidopsis.
AB  - Tightly controlled spatiotemporal specificity of gene expression is intrinsic to
      developmental and adaptation responses of living systems throughout the kingdoms.
      Forward genetic screens employing well-characterized reporter lines can be used
      to identify as yet unknown genetic factors driving specific aspects of individual
      regulatory pathways. However, such screens are demanding with respect to data
      acquisition and analysis from thousands of mutant lines. Here, we describe a
      method that allows screening of a mutagenized GUS reporter line in Arabidopsis
      using an automated microscopy imaging system as a tool for rapid and efficient
      identification of mutants with modified expression profile for a gene of
      interest. 

PMID- 24132419
TI  - Image analysis: basic procedures for description of plant structures.
AB  - This chapter gives examples of basic procedures of quantification of plant
      structures with the use of image analysis, which are commonly employed to
      describe differences among experimental treatments or phenotypes of plant
      material. Tasks are demonstrated with the use of ImageJ, a widely used public
      domain Java image processing program. Principles of sampling design based on
      systematic uniform random sampling for quantitative studies of anatomical
      parameters are given to obtain their unbiased estimations and simplified "rules
      of thumb" are presented. The basic procedures mentioned in the text are (1)
      sampling, (2) calibration, (3) manual length measurement, (4) leaf surface area
      measurement, (5) estimation of particle density demonstrated on an example of
      stomatal density, and (6) analysis of epidermal cell shape. 

PMID- 24132420
TI  - Identifying subcellular protein localization with fluorescent protein fusions
      after transient expression in onion epidermal cells.
AB  - Most biochemical functions of plant cells are carried out by proteins which act
      at very specific places within these cells, for example, within different
      organelles. Identifying the subcellular localization of proteins is therefore a
      useful tool to narrow down the possible functions that a novel or unknown protein
      may carry out. The discovery of genetically encoded fluorescent markers has made
      it possible to tag specific proteins and visualize them in vivo under a variety
      of conditions. This chapter describes a simple method to use transient expression
      of such fluorescently tagged proteins in onion epidermal cells to determine their
      subcellular localization relative to known markers. 

PMID- 24132421
TI  - Visualizing and quantifying the in vivo structure and dynamics of the Arabidopsis
      cortical cytoskeleton using CLSM and VAEM.
AB  - The cortical microtubules, and to some extent also the actin meshwork, play a
      central role in the shaping of plant cells. Transgenic plants expressing
      fluorescent protein markers specifically tagging the two main cytoskeletal
      systems are available, allowing noninvasive in vivo studies. Advanced microscopy
      techniques, in particular confocal laser scanning microscopy (CLSM) and variable
      angle epifluorescence microscopy (VAEM), can be nowadays used for imaging the
      cortical cytoskeleton of living cells with unprecedented spatial and temporal
      resolution. With the aid of suitable computing techniques, quantitative
      information can be extracted from microscopic images and video sequences,
      providing insight into both architecture and dynamics of the cortical
      cytoskeleton. 

PMID- 24132422
TI  - Sequential replicas for in vivo imaging of growing organ surfaces.
AB  - Sequential replica method facilitates in vivo imaging of plant surface and
      provides data sufficient for detailed computation of geometry and growth. It
      enables obtaining a series of high-resolution images visualizing details of the
      examined surface. Series of molds, made in dental polymer, representing the
      examined surface are used to obtain casts in epoxy resin, which are in turn
      observed by scanning electron microscopy, while the structure itself remains
      intact. Images obtained from casts can be further used for data extraction,
      comprising 3D reconstruction and computation of local geometry and cell growth
      parameters. The sequential replica method is a universal method and can be
      applied to image complex shapes of a range of structures, like meristems,
      flowers, stems, leaves, or various types of trichomes. Different plant species
      growing in various conditions can be studied. 

PMID- 24132423
TI  - Time-lapse imaging of developing meristems using confocal laser scanning
      microscope.
AB  - Analysis of shoot meristem shape and gene expression pattern has been conducted
      in many species over the past decades. Recent live imaging techniques have
      allowed an unprecedented accumulation of data on the biology of meristematic
      cells, as well as a better understanding of the molecular and biophysical
      mechanisms behind shape changes in this tissue. Here we describe in detail how to
      prepare shoot apices of both Arabidopsis and tomato, in order to image them over
      time using a confocal microscope equipped with a long-distance water-dipping
      lens. 

PMID- 24132424
TI  - Quantifying cell shape and gene expression in the shoot apical meristem using
      MorphoGraphX.
AB  - Confocal microscopy is a technique widely used to live-image plant tissue. Cells
      can be visualized by using fluorescent probes that mark the cell wall or plasma
      membrane. This enables the confocal microscope to be used as a 3D scanner with
      submicron precision. Here we present a protocol using the 3D image processing
      software MorphoGraphX (http://www.MorphoGraphX.org) to extract the surface
      geometry and cell shapes in the shoot apex. By segmenting cells over consecutive
      time points, precise growth maps of the shoot apex can be produced. It is also
      possible to tag a protein of interest with a fluorescent marker and quantify
      protein expression at the cellular level.

PMID- 24132425
TI  - Mechanical measurements on living plant cells by micro-indentation with cellular
      force microscopy.
AB  - Indentation methods on the micro- and nanoscale are increasingly used to assess
      mechanical properties of living plant tissues. These techniques rely on recording
      the force resulting from indenting the cell surface with a small probe. Depending
      on the scale of indentation and the indenter shape, force-indentation data will
      reflect several factors such as cell wall elasticity, turgor pressure, cell and
      tip geometry, and contact angle. Cellular force microscopy is a micro-indentation
      method that was designed to precisely measure and apply forces on living plant
      cells. Here we explain how to use this method to map the apparent stiffness in
      single cells and tissues. 

PMID- 24132426
TI  - High-pressure freezing and low-temperature processing of plant tissue samples for
      electron microscopy.
AB  - Use of electron tomography methods improves image resolution of transmission
      electron microscopy especially in the z-direction, enabling determination of
      complicated 3D structures of organelles and cytoskeleton arrays. The increase in
      resolution necessitates preservation of cellular structures close to the native
      states with minimum artifacts. High-pressure freezing (HPF) that immobilizes
      molecules in the cell instantaneously has been used to avoid damages caused by
      convention chemical fixation. Despite the advantages of HPF, cells could still be
      damaged during dissection prior to HPF. Therefore, it is critical to isolate
      cells/tissues of interest quickly and carefully. The samples frozen by HPF are
      often processed by freeze substitution (FS), and FS should be carried out under
      appropriate conditions. Here we describe dissection, HPF, and FS methods that we
      have utilized to prepare plant samples for electron tomography/immuno-electron
      microscopy. 

PMID- 24132427
TI  - Reconstructing plant cells in 3D by serial section electron tomography.
AB  - In micrographs acquired with a transmission electron microscope, 3-dimensional
      (3D) objects are superimposed onto a 2D screen. This reduction in dimension
      necessarily leads to a degradation of image resolution. To overcome this problem,
      3D microscopy techniques, such as tomography and single particle analysis, have
      been developed. Tomography has been used to visualize cells in 3D, and single
      particle analysis has been used to investigate macromolecules and viral
      particles. In this chapter we will describe how we have collected tilting series
      micrographs from plant cells and how we have reconstructed the cellular volumes
      using dual axis electron tomography. 

PMID- 24132428
TI  - Imaging plant nuclei and membrane-associated cytoskeleton by field emission
      scanning electron microscopy.
AB  - Scanning electron microscopy (SEM) is a powerful technique that can image exposed
      surfaces in 3D. Modern scanning electron microscopes, with field emission
      electron sources and in-lens specimen chambers, achieve resolutions of better
      than 0.5 nm and thus offer views of ultrastructural details of subcellular
      structures or even macromolecular complexes. Obtaining a reliable image is,
      however, dependent on sample preparation methods that robustly but accurately
      preserve biological structures. In plants, exposing the object of interest may be
      difficult due to the existence of a cell wall. This protocol shows how to isolate
      plant nuclei for SEM imaging of the nuclear envelope and associated structures
      from both sides of the nuclear envelope in cultured cells as well as in leaf or
      root cells. Further, it provides a method for uncovering membrane-associated
      cytoskeletal structures. 

PMID- 24132429
TI  - Immunogold labeling of resin-embedded electron microscopical sections.
AB  - Knowledge about the spatio-temporal distribution patterns of proteins and other
      molecules of the cell is essential for understanding their function. A widely
      used technique is immunolabeling which uses specific antibodies to reveal the
      distribution of molecular components at various structural levels. Electron
      microscopy offers the highest resolution of morphological techniques and is thus
      an indispensable tool for the analysis of molecule distribution patterns at the
      subcellular level. In this chapter we describe a routine method for labeling
      ultrathin sections of resin-embedded material with antibodies conjugated to
      colloidal gold. 

PMID- 24132430
TI  - Live cell imaging of Arabidopsis root hairs.
AB  - Root hairs are tubular extensions from the root surface that expand by tip
      growth. This highly focused type of cell expansion, combined with position of
      root hairs on the surface of the root, makes them ideal cells for microscopic
      observation. This chapter describes the method that is routinely used in our
      laboratory for live cell imaging of Arabidopsis root hairs. 

PMID- 24132431
TI  - Morphological analysis of cell growth mutants in Physcomitrella.
AB  - This protocol describes a quantitative analysis of the morphology of small plants
      from the moss Physcomitrella patens. The protocol can be used for the analysis of
      growth phenotypes produced by transient RNA interference or for the analysis of
      stable mutant plants. Information is presented to guide the investigator in the
      choice of vectors and basic conditions to perform transient RNA interference in
      moss. Detailed directions and examples for fluorescence image acquisition of
      small regenerating moss plants are provided. Instructions for the use of an
      ImageJ-based macro for quantitative morphological analysis of these plants are
      also provided. 

PMID- 24132432
TI  - Plant cell lines in cell morphogenesis research.
AB  - Plant organs and tissues consist of many various cell types, often in different
      phases of their development. Such complex structures do not allow direct studies
      on behavior of individual cells. In contrast, populations of in vitro-cultured
      plant cells represent valuable tool for studying processes on a single-cell
      level, including cell morphogenesis. Here we describe characteristics of well
      established model tobacco and Arabidopsis cell lines and provide detailed
      protocol on their cultivation, characterization, and genetic transformation. 

PMID- 24132433
TI  - Antisense oligodeoxynucleotide-mediated gene knockdown in pollen tubes.
AB  - Specific gene knockdown mediated by the antisense oligodeoxynucleotides (AODNs)
      strategy recently emerged as a rapid and effective tool for probing gene role in
      plant cells, particularly tip-growing pollen tubes. Here, we describe the
      protocol for the successful employment of AODN technique in growing tobacco
      pollen tubes, covering AODN design, application, and analysis of the results. We
      also discuss the advantages and drawbacks of this method. 

PMID- 24132434
TI  - Lab-on-a-chip for studying growing pollen tubes.
AB  - A major limitation in the study of pollen tube growth has been the difficulty in
      providing an in vitro testing microenvironment that physically resembles the in
      vivo conditions. Here we describe the development of a lab-on-a-chip (LOC) for
      the manipulation and experimental testing of individual pollen tubes. The design
      was specifically tailored to pollen tubes from Camellia japonica, but it can be
      easily adapted for any other species. The platform is fabricated from
      polydimethylsiloxane (PDMS) using a silicon/SU-8 mold and makes use of
      microfluidics to distribute pollen grains to serially arranged microchannels. The
      tubes are guided into these channels where they can be tested individually. The
      microfluidic platform allows for specific testing of a variety of growth
      behavioral features as demonstrated with a simple mechanical obstacle test, and
      it permits the straightforward integration of further single-cell test assays. 

PMID- 24132435
TI  - Laser microdissection of plant cells.
AB  - Different plant cell types express unique transcriptomes, proteomes, and
      metabolomes. Therefore, the isolation of specific cell types prior to molecular
      analyses is important to understand the specification, differentiation, and
      function of these cells. Isolation of specific plant cell types from composite
      organs can be achieved by laser microdissection (LMD). A wide variety of methods
      to fix and embed tissues prior to LMD and downstream molecular analyses have been
      developed for different plant species and tissues. The present review summarizes
      and highlights the most recently applied LMD approaches in plant science. 

PMID- 24132436
TI  - Optical trapping in plant cells.
AB  - Optical tweezers allow noninvasive manipulation of subcellular compartments to
      study their physical interactions and attachments. By measuring (delay of)
      displacements, (semi-)quantitative force measurements within a living cell can be
      performed. In this chapter, we provide practical tips for setting up such
      experiments paying special attention to the technical considerations for
      integrating optical tweezers into a confocal microscope. Next, we describe some
      working protocols to trap intracellular structures in plant cells. 

PMID- 24132437
TI  - Heterologous expression in budding yeast as a tool for studying the plant cell
      morphogenesis machinery.
AB  - The budding yeast (Saccharomyces cerevisiae) can serve as a unique experimental
      system for functional studies of heterologous genes, allowing not only
      complementation of readily available yeast mutations but also generation of
      overexpression phenotypes and in some cases also rescue of such phenotypes. Here
      we summarize the main considerations that have to be taken into account when
      using the yeast expression system for investigating the function of plant genes
      participating in cell morphogenesis; outline the strategies of experiment
      planning, yeast strain selection (or construction), and expression vector choice;
      and provide detailed protocols for yeast transformation, transformant selection,
      and phenotype evaluation. 

PMID- 24132438
TI  - Performance outcomes in professional hockey players following arthroscopic
      treatment of FAI and microfracture of the hip.
AB  - PURPOSE: Previous studies report professional athletes return to play following
      arthroscopic microfracture of the hip for chondral defects. Our hypothesis is
      that professional hockey players undergoing arthroscopic microfracture for
      chondral defects of the hip achieve the same performance they had pre-injury and
      compared to matched controls. METHODS: Seventeen professional hockey players
      underwent arthroscopic microfracture for an Outerbridge grade IV chondral lesion.
      Concomitant procedures for labral pathology or FAI were included. Performance
      data for the full season preceding and following index procedure were analysed,
      in addition to two matched control players per subject. Data were collected at
      two points, 2 years apart. RESULTS: Eighty-two per cent (14/17) of players who
      underwent arthroscopic microfracture returned to play. The year prior to injury
      for the 14 players who returned was compared to the average of their individual
      controls. There was no statistical difference between the groups for age, number
      of seasons in the league, games played, time on ice, points, save percentage, and
      shots against goal. Post-operatively, there was no statistical difference between
      the treatment and control groups regarding performance measures. There was a
      trend towards a decrease in games played and points post-operatively compared
      with controls. The treatment group decreased 11 games played, while the controls
      decreased five games. The treatment group also decreased 14 points, while the
      controls decreased three points for the season. CONCLUSIONS: Professional hockey
      players with a discrete, full-thickness chondral defect of the hip are able to
      return to elite performance level following an arthroscopic microfracture
      procedure when compared to pre-injury outcomes and controls.

PMID- 24132440
TI  - Hyperamylasaemia: pathognomonic to pancreatitis?
AB  - An 82-year-old woman, presented with a history of vomiting, abdominal mass and a
      significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal
      ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis
      as is often associated with a raised amylase. The patient underwent bilateral
      ovariectomy and hysterectomy and made a good recovery. 

PMID- 24132441
TI  - Acute carotid stenting for treatment of stuttering transient ischemic attacks
      after recent carotid endarterectomy.
AB  - Carotid endarterectomy (CEA) is the established standard to treat occlusive
      extracranial atherosclerotic carotid disease. Complications of CEA must be
      recognized and dealt with efficiently due to the potentially catastrophic
      neurologic sequelae. A 67-year-old African American man was transferred from an
      outside hospital for an acute stroke. He had initially presented with a small
      right frontal subcortical infarct and had undergone a right CEA 2 days prior to
      transfer. He had a fluctuating examination with left-sided hemiplegia to slight
      hemiparesis and inconsistent neglect. Head CT demonstrated a watershed infarct of
      the right hemisphere. CT angiography demonstrated high grade stenosis at the
      distal aspect of the CEA anastomosis. He was promptly taken for angiography and
      underwent acute stenting of the right internal carotid artery. This case
      demonstrates that carotid artery stenting is a safe management strategy for the
      treatment of complications associated with failed distal anastomosis during CEA. 

PMID- 24132442
TI  - Von Recklinghausen disease (neurofibromatosis type 1): beyond skin involvement.

PMID- 24132443
TI  - Isolated paroxysmal dysarthria caused by a single demyelinating midbrain lesion.
AB  - Paroxysmal dysarthria is an unusual condition characterised by brief episodes of
      dysarthria with the sudden onset and frequent recurrence. It has been mainly
      reported in multiple sclerosis and an association with midbrain lesions has been
      claimed; however, most of the reported patients had multiple brain alterations so
      it was difficult to associate this symptom with a specific lesion site. We
      illustrate the cases of two patients with an isolated demyelinating midbrain
      lesion presenting paroxysmal dysarthria as the only symptom; both participants
      had oligoclonal bands in the cerebrospinal fluid and an unremarkable follow-up.
      Both patients had benefit from carbamazepine treatment, similarly to previously
      reported cases. Our report confirms that a demyelinating midbrain lesion is
      sufficient to provoke paroxysmal dysarthria. It is noteworthy that an erroneous
      diagnosis of psychogenic disorders was initially made in both cases, highlighting
      the importance not to underestimate isolated paroxysmal symptoms in clinical
      practice. 

PMID- 24132444
TI  - Vancomycin-induced thrombocytopaenia in a patient with severe pancreatitis.
AB  - Vancomycin-induced thrombocytopenia is a rare side effect of a commonly used drug
      that may cause life-threatening disease. A 51-year-old man was treated for an
      episode of acute severe alcohol-induced pancreatitis complicated by development
      of a peripancreatic fluid collection. He developed fever of unknown origin and
      was treated with intravenous vancomycin and piperacillin with tazobactam. On day
      6 of vancomycin therapy his platelet count dropped to 46*10(9)/L (237*10(9)/L on
      day 1 of treatment) and by day 8 of therapy platelets had fallen to a nadir of
      9*10(9)/L. The patient at this stage displayed a florid purpuric rash and
      haematoma formation on attempted intravenous cannulation. A clinical diagnosis of
      vancomycin-induced thrombocytopaenia was made and the drug withdrawn. After 3
      days a significant improvement in the platelet count was noted, rising to 56 *
      10(9)/L. Immunofluorescence testing (PIFT) ruled out teicoplanin and heparin as
      causes of drug-induced thrombocytopenia.

PMID- 24132445
TI  - An interesting rash following bowel and abdominal wall transplantation.

PMID- 24132446
TI  - Non-tuberculous mycobacterial infection of the parotid gland in an
      immunocompetent elderly patient.
AB  - We experienced an extremely rare case in which combined antibacterial therapy for
      a non-tuberculous mycobacteria (NTM) infection of the parotid gland achieved a
      favourable outcome in an elderly immunocompetent patient. Although a 79-year-old
      man, who presented with swelling and fistula formation in the left parotid gland
      region, initially received combined antituberculous therapy due to a positive
      result of acid-fast staining, the lesion did not respond to these agents.
      Thereafter, since the culture examination did not detect Mycobacterium
      tuberculosis or NTM, we excluded tuberculosis and considered the possibility of
      an NTM infection caused by a rare mycobacterial species. Therefore, we switched
      to the clarithromycin-based antibacterial treatment for eight consecutive months
      without a surgical intervention, resulting in the complete disappearance of the
      lesion and no evidence of recurrence detected for 4 years. This conservative
      chemotherapy might be a feasible alternative to a surgical intervention for
      treatment against NTM infections of the parotid gland. 

PMID- 24132447
TI  - Lung-sparing approach for an intrapulmonary bronchogenic cyst involving the right
      upper and middle lobes.
AB  - Intrapulmonary bronchogenic cysts (IBC) represent 20% of abnormal budding of the
      respiratory tract. Lobectomy is the recommended treatment for IBC in symptomatic
      adults. We presented a case of a patient with an IBC involving the right upper
      and middle lobes (RUL-RML). A 27-year-old woman presented with a 2-month history
      of thoracic pain, cough and haemoptysis. An opacity was found on the chest X-ray.
      High-resolution CT/MRI showed a 7*4.5 cm marginated mass with an air bubble
      inside. A video-assisted thoracoscopic surgery was performed. The cyst was
      neither palpable nor visible. An intraoperative ultrasonography localised the
      cyst involving the RUL-RML. The lung above the cyst was incised, and a greenish
      mucoid content was aspirated. A branch of the superior pulmonary vein was
      visible. The remaining cystic wall was cauterised. The patient was discharged on
      day 4. Histology confirmed the IBC. The patient is asymptomatic at a 16-month
      follow-up. The lung-sparing operation in a young woman with IBC involving the RUL
      RML has been beneficial. A long-term follow-up is mandatory. 

PMID- 24132448
TI  - Spinal neurocytoma with extensive syringohydromyelia.

PMID- 24132449
TI  - Umbilical paracentesis for acute hernia reduction in cirrhotic patients.
AB  - Emergent repair of umbilical hernias in cirrhotic patients is associated with a
      high risk for morbidity and mortality. We propose a new technique, umbilical
      paracentesis, for reduction of incarcerated hernias in the patient with ascites.
      Under ultrasound guidance, removal of ascitic fluid from the umbilical hernia sac
      can reduce the local pressure and thereby allow for easy hernia reduction, thus
      avoiding the need for an emergent operation. 

PMID- 24132450
TI  - Pulmonary apical fibrosis in a patient treated earlier for breast cancer.

PMID- 24132451
TI  - Case of paraspinal collection due to Burkholderia pseudomallei.

PMID- 24132452
TI  - Cumbo sign.

PMID- 24132453
TI  - Traumatic carotid-cavernous fistula: excellent demonstration on 3D CT
      angiography.

PMID- 24132454
TI  - Porphyrin-silica microparticle conjugates as an efficient tool for the
      photosensitised disinfection of water contaminated by bacterial pathogens.
AB  - A tetracationic meso-substituted amphiphilic porphyrin (abbreviated as C14) was
      encapsulated within silica microparticles to yield a conjugate with a mean
      particle diameter of ca. 0.9 MUm. The conjugate displayed a complete stability
      for at least 3 months when suspended in a neutral aqueous medium. The
      encapsulated C14 underwent a limited photobleaching when the conjugate was
      exposed to full spectrum visible light. Illumination of the silica microparticle
      bound C14 by visible light resulted in the generation of singlet oxygen and
      induced a decrease in the survival of 4 log for a 20 min irradiation of the Gram
      positive bacterium meticillin-resistant Staphylococcus aureus (MRSA) and a 30 min
      irradiation of the Gram-negative bacterium Escherichia coli (E. coli). Under
      identical experimental conditions photoexcited free C14 caused a decrease in
      viability of 5 log for MRSA and 6 log for E. coli. When the conjugate loaded with
      12 MUM C14 was added to a water sample contaminated with MRSA (10(8) cells per
      ml) a tight association of the bacterial cells with the silica microparticle
      porphyrin system was achieved. Subsequent illumination of the conjugate with
      visible light (30 min, 100 mW cm(-2)) caused a 3 log reduction in the population
      of MRSA cells in the water sample. Importantly, the conjugate was readily
      recovered by filtration of the aqueous suspension and shown to maintain a high
      antibacterial photoactivity when introduced into a new MRSA-contaminated medium
      and irradiated. 

PMID- 24132455
TI  - Integrated optical waveguide and photodetector arrays based on comb-like ZnO
      structures.
AB  - On-chip integrations of photonic waveguides and high-performance electrically
      driven devices, by combining different active or passive optical components, are
      imperative towards the advancement of nanophotonic circuitry systems. We
      experimentally demonstrate the collective optical functionalities of ZnO
      microstructures towards designing an integrated photonic system by combining the
      optical waveguiding and detection properties. Comb-like microstructures composed
      of periodic arrays of smooth, single-crystalline ZnO nanowires are synthesized
      for these purposes. We demonstrate that ZnO comb structures could be used as
      optical waveguides, which can manipulate the blue, green, and red laser beams to
      an interconnected waveguide array. These results are substantiated by extensive
      investigation of waveguiding properties of single, stacked or crossbar nanowires,
      and different branched microstructures. These waveguide arrays can be
      successfully coupled with another ZnO comb-based photodetector and the collective
      performances of the integrated optical micro-device units are investigated in
      detail. This study shows that ZnO comb-based optical waveguide arrays have the
      great potential to be used as a bottom-up strategy for the construction of
      various miniaturized photonic demultiplexer systems. 

PMID- 24132456
TI  - Methane emission of Santa Ines sheep fed cottonseed by-products containing
      different levels of gossypol.
AB  - The aim of this study was to evaluate the methane (CH4) emission of Santa Ines
      sheep fed cottonseed by-products, verifying if the gossypol content of these
      feedstuffs affects CH4 emission. Twelve late-lactating Santa Ines sheep (44.8 +/-
      7.5 kg body weight (BW)) were allocated in metabolic cages for an experimental
      period of 19 days, 14 days for adaptation and 5 days for measuring CH4 emission
      and dry matter intake (DMI). The animals were divided into four treatments,
      established in accordance with the cottonseed by-product used in concentrate
      formulation: Control (CON - no cottonseed by-product), Whole cottonseed (WCS),
      Cottonseed cake (CSC), and Cottonseed meal (CSM). The free gossypol level of the
      concentrates were 0, 1,276, 350, and 190 ppm for CON, WCS, CSC, and CSM,
      respectively. Also, the animals received Cynodon dactylon cv. Coast Cross hay,
      water, and mineral salt ad libitum. The ether extract content of the diets was
      balanced between treatments by including soybean oil in concentrates. The
      technique used to measure the CH4 emission was the sulfur hexafluoride (SF6)
      tracer technique, and the gas samples collected were quantified by analysis in
      gas chromatography system. The CH4 emission was evaluated considering the daily
      emission (g CH4/day); DMI (g CH4/kg DMI); and BW (g CH4/kg BW). No statistical
      difference was found (P > 0.05) between treatments for DMI and CH4 parameters. In
      the regression analysis, no significant relation (P > 0.05) between gossypol
      content and CH4 emission was observed. These results suggest that gossypol does
      not affect rumen methanogenesis. 

PMID- 24132457
TI  - Religion and health: anxiety, religiosity, meaning of life and mental health.
AB  - We examined the association among anxiety, religiosity, meaning of life and
      mental health in a nonclinical sample from a Chinese society. Four hundred fifty
      one Taiwanese adults (150 males and 300 females) ranging in age from 17 to 73
      years (M = 28.9, SD = 11.53) completed measures of Beck Anxiety Inventory,
      Medical Outcomes Study Health Survey, Perceived Stress Scale, Social Support
      Scale, and Personal Religiosity Scale (measuring religiosity and meaning of
      life). Meaning of life has a significant negative correlation with anxiety and a
      significant positive correlation with mental health and religiosity; however,
      religiosity does not correlate significantly anxiety and mental health after
      controlling for demographic measures, social support and physical health. Anxiety
      explains unique variance in mental health above meaning of life. Meaning of life
      was found to partially mediate the relationship between anxiety and mental
      health. These findings suggest that benefits of meaning of life for mental health
      can be at least partially accounted for by the effects of underlying anxiety.

PMID- 24132458
TI  - Attending religious services and its relationship with coronary heart disease and
      related risk factors in older adults: a qualitative study of church pastors' and
      parishioners' perspectives.
AB  - A qualitative study was undertaken to explain findings of a cross-sectional study
      of Canadian Community Health Survey (CCHS) 4.1 data showing older persons who
      attend religious services more than once a week, compared to persons who do not
      attend at all, have lower prevalences of coronary heart disease (CHD), diabetes
      and high blood pressure. Twelve semi-structured interviews with ordained pastors
      and three focus groups with older parishioners from Canadian churches were
      conducted. Interviews were transcribed and analyzed for emergent themes through a
      process of direct content analysis. All participants claimed that religious
      service attendance (RSA): (1) enhances mental health; (2) provides social support
      and activities; and (3) promotes health and lifestyle behaviours that lower CHD
      risk. These three themes appear to be underlying mechanisms that help to explain
      the inverse association between RSA and the prevalence of adverse health outcomes
      found in the CCHS 4.1 data. 

PMID- 24132459
TI  - The world can look better: enhancing beauty experience with brain stimulation.
AB  - Aesthetic appreciation is part of our everyday life: it is a subjective judgment
      we make when looking at a painting, a landscape, or--in fact--at another person.
      Neuroimaging and electrophysiological evidence suggests that the left
      dorsolateral prefrontal cortex (DLPFC) plays a critical role in aesthetic
      judgments. Here, we show that the experience of beauty can be artificially
      enhanced with brain stimulation. Specifically, we show that aesthetic
      appreciation of representational paintings and photographs can be increased by
      applying anodal (excitatory) transcranial direct current stimulation on the left
      DLPFC. Our results thus show that beauty is in the brain of the beholder, and
      offer a novel view on the neural networks underlying aesthetic appreciation.

PMID- 24132460
TI  - Can we predict the clinical outcomes of genitourinary trauma patients and offer
      them an evidence-based support? The case for telemedicine network.

PMID- 24132461
TI  - Abundant in vitro expression of the oncofetal ED-B-containing fibronectin
      translates into selective pharmacodelivery of (131)I-L19SIP in a prostate cancer
      patient.
AB  - PURPOSE: The extradomain B of fibronectin (ED-B) is a promising vascular target
      for selective pharmacodelivery in cancer patients. We analyzed a large series of
      prostatectomies from patients with prostate cancer, hyperplastic prostate
      disease, and normal prostates to study extent and tumor-selectivity of ED-B
      expression. METHODS: Using immunohistology, 68 adenocarcinomas of the prostate or
      prostate cancer-inflicted lymph nodes, 4 samples of benign prostatic hyperplasia,
      and 6 normal prostate glands were studied for ED-B expressing newly formed blood
      vessels. Further, we treated an advanced prostate cancer patient with the anti-ED
      B antibody (131)I-L19SIP to study in vivo target accessibility. RESULTS: ED-B
      positive blood vessels were found significantly more frequent in prostate cancers
      as compared with peritumoral prostate tissues or normal prostate glands,
      independent of tumor differentiation. The ED-B-positive blood vessels' density
      was 97 (+/-23), 65 (+/-9), and 59 (+/-9)/mm(2) in G3, G2, and G1 prostate
      cancers, respectively, and 7 (+/-5)/mm(2) in normal prostate glands. In high
      grade (G3) prostate cancers, also the peritumoral tissue showed a higher density
      of ED-B vessels than normal prostate glands. Similar results were obtained when
      ED-B-positive vessel density was expressed as a fraction of CD34-positive vessel
      density. Finally, selective uptake of ED-B-binding (131)I-L19SIP to tumor lesions
      was found in an advanced prostate cancer patient by whole-body planar
      scintigraphy. CONCLUSIONS: ED-B-positive blood vessels were found to a large
      extent in prostate cancer tissues, but only rarely in normal prostates or benign
      prostatic hyperplasia. Whole-body planar scintigraphy in a prostate cancer
      patient confirmed selective uptake of (131)I-L19SIP in the prostate cancer
      tissues, qualifying ED-B as a promising target for selective pharmacodelivery of
      anticancer agents in prostate cancer.

PMID- 24132462
TI  - Individual and work-related predictors of work outcomes related to sustainable
      employment among male shift and day workers.
AB  - OBJECTIVES: The aim of this study was to examine which individual and work
      related characteristics predict work outcomes related to sustainable employment
      among male shift and day workers. METHODS: Between 1 September 2005 and 31
      December 2009, data on individual and work-related characteristics of N=5640
      employees of Tata Steel in the Netherlands were retrieved from the Occupational
      Health Service and company registers. Work outcomes related to sustainable
      employment were (i) temporarily being placed in less strenuous work, (ii)
      sickness absence >=6 weeks, and (iii) leaving the organization. Cox proportional
      hazard analyses were performed for all outcome measures. RESULTS: Similar
      predictors were found for shift and day workers although some differences were
      observed. For shift workers, high blood pressure and cardiovascular disease were
      important predictors for sickness absence. For day workers, insomnia was an
      important predictor of sickness absence >=6 weeks. CONCLUSIONS: Similar
      predictors in magnitude and direction were found for work outcomes related to
      sustainable employment among shift and day workers. Interventions aimed at
      enhancing sustainable employability should focus on individual and work-related
      characteristics.

PMID- 24132463
TI  - The psychosocial atmosphere in community-based activity centers for people with
      psychiatric disabilities: visitor and staff perceptions.
AB  - This study investigated how visitors and staff in community-based activity
      centers in Sweden perceived the psychosocial atmosphere and whether this could be
      explained by the centers' orientation (work-oriented versus meeting place
      oriented centers). Eighty-eight visitors and 37 staff members at three work
      oriented and three meeting place-oriented centers participated. The Community
      oriented Programs Environmental Scale was used to estimate the psychosocial
      atmosphere. The result showed that the psychosocial atmosphere at the centers was
      in accordance with a supportive ward atmosphere profile. Visitors and staff
      perceived several aspects of the psychosocial atmosphere differently, especially
      in the meeting place-oriented centers. The visitors in the meeting place-oriented
      centers did not perceive the psychosocial atmosphere differently from those
      visiting the work-oriented centers. The results indicated that the psychosocial
      atmosphere at the centers was in line with what previous research has shown to be
      beneficial for visitors regarding outcome and favorable for promoting a good
      therapeutic alliance and a good functioning in daily life. 

PMID- 24132464
TI  - Pb and Cd bioaccumulations in the habitat and preys of red-crowned cranes (Grus
      japonensis) in Zhalong Wetland, Northeastern China.
AB  - Pb and Cd concentrations in the habitat and preys of the red-crowned crane (i.e.,
      reed rhizomes and three typical aquatic animal families (Perccottus glehni
      Dybowski, Carassius auratus Linnaeus, and Viviparidae)) were analyzed to examine
      the impact of these hazards on red-crowned cranes in northeastern China. Results
      indicated that Pb and Cd concentrations in the preys of the red-crowned cranes
      were elevated via food chain. Most of the detected Pb and Cd contents in the
      sediments were above the natural background level, ranging from 9.85 to 129.72
      ppm and 1.23 to 10.63 ppm (dry weight), respectively. Cd geo-accumulation index
      at all sites were larger than 3, even reached 5.22, suggesting serious pollution
      in this region. Three common water animal families were detected to contain heavy
      metals, following the order of increasing concentrations: primary consumers
      (i.e., Viviparidae and Carassius auratus Linnaeus) < secondary consumers (i.e.,
      Perccottus glehni Dybowski). Pb and Cd concentrations in the buffer zone are
      significantly higher than in the core area and being elevated in the food chain.
      The molten feathers of the red-crowned cranes showed the highest toxic metal
      concentrations of Pb (2.09 to 5.81 ppm) and Cd (1.42 to 3.06 ppm) compared with
      the feces produced by cranes and residual eggshell left by water fowls.
      Exceptionally high Pb and Cd concentrations in the cranes and their preys were
      thought to be associated with their habitat.

PMID- 24132465
TI  - Are metals accumulated in human hair affected by naturally occurring asbestos
      fiber contamination? A case study from a rural area of china.
AB  - Little is known about the link between metals accumulated in human and asbestos
      fiber contamination in the environment. Therefore, hair samples of 368 subjects
      (128 males and 240 females) from a rural area contaminated by crocidolite
      asbestos fibers were collected to investigate the distributions of 17 metals
      accumulated in human. The results showed that the mean concentrations of As, Al,
      Ba, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Na, Ni, Pb, Sr, and Zn in hair of the
      total subjects were 0.23, 23.36, 4.33, 0.11, 0.05, 0.70, 10.53, 29.74, 0.37,
      241.57, 3.52, 0.08, 153.21, 0.72, 4.26, 10.96, and 113.35 mg/kg, respectively.
      Moreover, approximately 86.14, 52.17, 73.91, 85.05, 80.98, 74.46, and 53.80 % of
      the hair samples of the total subjects contained much higher concentrations of
      Al, Ba, Fe, Mg, Mn, Na, and Sr compared with the highest reference values,
      respectively. The mean concentrations of the determined metals (except for As,
      Co, Cr, Hg, and Mo) significantly varied among different age groups for both male
      and females. The results of correlation analysis and cluster analysis revealed
      that strong correlations were found between Al, Fe, Zn, Mg, and Na accumulated in
      human from the study area. These might suggest that Al, Ba, Fe, Mg, Mn, Na, and
      Sr were significantly derived from contamination of crocidolite asbestos fibers.
      Zn, Mg, and Na might also originate from diet. However, Cd, Mo, Co, As, Cr, Hg,
      Ni, Mn, Pb, and Ba accumulated in human seemed to be mainly derived from soil. It
      can be concluded that metals accumulated in human hair have a link with asbestos
      fiber contamination in the environment.

PMID- 24132466
TI  - A new instrument for intrahepatic access of Glissonian pedicles during anatomical
      liver resections.
AB  - The knowledge of liver anatomy has led to a rapid evolution based on the
      intrahepatic distribution of the portal pedicle. One great advance in liver
      surgery was the used of segment-based liver resections. Techniques based with
      intrahepatic Glissonian access of portal pedicles were described to safely
      perform anatomical liver resections. We have earlier described a standardized
      intrahepatic access to right and left liver segments' pedicles without hilar
      dissection for anatomical hepatectomies. To improve the intrahepatic Glissonian
      technique, we designed a new atraumatic instrument for liver pedicle retrieval
      based on the anatomical liver landmarks. This new instrument was successfully
      employed in seventeen consecutive liver resections with minimum blood loss and
      without any complications related to its use. This new instrument, atraumatic
      retriever, replaces the right angle dissector or Gray clamp. The new instrument
      can slide easily and smoothly around Glissonian pedicle with a simple movement.
      This new instrument is a useful adjunct for performing intrahepatic access for
      liver resections. It can also be used to compass delicate anatomical structures
      such as esophagus and major abdominal vessels. The retriever can further be used
      in other common situations, including access for Pringle maneuver, encircling
      proximal esophagus during total gastrectomies or esophagectomies, and access for
      total vascular exclusion of the liver. This instrument can also be adapted to be
      used for laparoscopic liver resections. 

PMID- 24132467
TI  - Correlation between outcome and instrumental findings after stapled transanal
      rectal resection for obstructed defecation syndrome.
AB  - OBJECTIVE: Several studies show that stapled transanal rectal resection (STARR)
      significantly improves constipation in most patients, while others remain
      symptomatic for obstructed defecation syndrome (ODS). The aim of the study was to
      analyze clinical, manometric, and endoanal ultrasonography results in order to
      find any possible correlation between clinical and instrumental data,
      particularly in dissatisfied patients, both for those who remain symptomatic for
      ODS and for patients with new-onset fecal disorders. PATIENTS AND METHODS: All
      patients underwent a preoperative and postoperative assessment based on clinical
      evaluation, proctoscopy, defecography, anorectal manometry, and endoanal
      ultrasonography. Furthermore, we asked patients about a subjective satisfaction
      grading of outcome. RESULTS: From January 2007 to December 2009, 103 patients
      were treated in our department with STARR for ODS. Postoperative endoanal
      ultrasound did not demonstrate any variations compared with the preoperative one.
      Postoperative scores showed statistically significant improvement, with respect
      to the preoperative value, with good and sufficient scores in 79.6% of patients,
      and an overall rate of satisfaction of 87.1%. Fecal disorders, including also the
      slightest alteration of continence, occurred in 24% of patients, in particular
      soiling 1.8%, urgency 7.4%, occasional gas leakage 5.5%, and liquid/solid leakage
      9.3%. Anorectal manometry revealed a statistically significant reduction only in
      sensitivity threshold and maximum tolerated volume compared to patients with no
      disorders of continence. CONCLUSION: Results indicate good satisfaction grading
      and a statistically significant improvement in scores of constipation. There is
      no close correlation between satisfaction grading and scores. Besides, the
      assessment of patient's satisfaction often does not match the objective
      functional outcome.

PMID- 24132468
TI  - In-office imaging capabilities among procedure-based specialty practices.
AB  - BACKGROUND: Stark law's in-office ancillary services exception permits physicians
      to furnish designated health services in the office, including advanced imaging.
      OBJECTIVES: To determine whether arrangements tailored to fit this loophole spur
      utilization. RESEARCH DESIGN: Cross-sectional. SUBJECTS: Procedure-based
      specialty clinics participating in the National Ambulatory Medical Care Survey.
      MEASURES: Using restricted data files (2006-2008), we identified specialty
      practices with on-site advanced imaging capabilities (ie, computed tomography,
      magnetic resonance imaging, and/or positron emission tomography). We then
      characterized these practices and the physicians who worked in them over a
      variety of factors. Finally, we performed multivariable regression to evaluate
      the association between imaging use and the availability of in-office imaging.
      RESULTS: Fourteen percent of practices performed advanced imaging on site. While
      this proportion remained stable over the study period for most specialties, it
      rose significantly among orthopedic surgery clinics from 13.6% to 31.3% (P = .023
      for the temporal trend). The availability of advanced imaging varied by practice
      organization and size. For instance, 32.6% of large single-specialty groups
      provided in-office imaging as compared to only 10.1% of solo/partnership
      practices. While less than a quarter of specialty visits were made to practices
      that offered advanced imaging, these locations generated a third of all advanced
      imaging studies. In fact, 1 in 11 visits (9.0%; 95% confidence interval = 6.8% to
      11.6%; P = .030) to them resulted in advanced imaging. CONCLUSIONS: The
      availability of in-office advanced imaging is associated with increased imaging
      use.

PMID- 24132469
TI  - A multicenter prospective cohort study on camera navigation training for key user
      groups in minimally invasive surgery.
AB  - BACKGROUND: Untrained laparoscopic camera assistants in minimally invasive
      surgery (MIS) may cause suboptimal view of the operating field, thereby
      increasing risk for errors. Camera navigation is often performed by the least
      experienced member of the operating team, such as inexperienced surgical
      residents, operating room nurses, and medical students. The operating room nurses
      and medical students are currently not included as key user groups in structured
      laparoscopic training programs. A new virtual reality laparoscopic camera
      navigation (LCN) module was specifically developed for these key user groups.
      METHODS: This multicenter prospective cohort study assesses face validity and
      construct validity of the LCN module on the Simendo virtual reality simulator.
      Face validity was assessed through a questionnaire on resemblance to reality and
      perceived usability of the instrument among experts and trainees. Construct
      validity was assessed by comparing scores of groups with different levels of
      experience on outcome parameters of speed and movement proficiency. RESULTS: The
      results obtained show uniform and positive evaluation of the LCN module among
      expert users and trainees, signifying face validity. Experts and intermediate
      experience groups performed significantly better in task time and camera
      stability during three repetitions, compared to the less experienced user groups
      (P < .007). Comparison of learning curves showed significant improvement of
      proficiency in time and camera stability for all groups during three repetitions
      (P < .007). CONCLUSION: The results of this study show face validity and
      construct validity of the LCN module. The module is suitable for use in training
      curricula for operating room nurses and novice surgical trainees, aimed at
      improving team performance in minimally invasive surgery.

PMID- 24132470
TI  - Heat sink phenomenon of bipolar and monopolar radiofrequency ablation observed
      using polypropylene tubes for vessel simulation.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is widely used for treating liver
      tumors; recurrence is common owing to proximity to blood vessels possibly due to
      the heat sink effect. We seek to investigate this phenomenon using unipolar and
      bipolar RFA on an egg white tumor tissue model and an animal liver model.
      MATERIALS AND METHODS: Temperature profiles during ablation (with and without
      vessel simulation) were studied, using both bipolar and unipolar RFA probes by 4
      strategically placed temperature leads to monitor temperature profile during
      ablation. The volume of ablated tissue was also measured. RESULTS: The volume
      ablated during vessel simulation confirmed the impact of the heat sink
      phenomenon. The heat sink effect of unipolar RFA was greater compared with
      bipolar RFA (ratio of volume affected 2:1) in both tissue and liver models. The
      volume ablated using unipolar RFA was less than the bipolar RFA (ratio of volume
      ablated = 1:4). Unipolar RFA achieved higher ablation temperatures (122 degrees C
      vs 98 degrees C). Unipolar RFA resulted in tissue damage beyond the vessel, which
      was not observed using bipolar RFA. CONCLUSION: Bipolar RFA ablates a larger
      tumor volume compared with unipolar RFA, with a single ablation. The impact of
      heat sink phenomenon in tumor ablation is less so with bipolar than unipolar RFA
      with sparing of adjacent vessel damage.

PMID- 24132471
TI  - Calculating optimal surveillance for detection of von Hippel-Lindau-related
      manifestations.
AB  - von Hippel-Lindau (VHL) mutation carriers develop benign and malignant tumors,
      requiring regular surveillance. The aim of this study was to calculate the
      optimal organ-specific age to initiate surveillance and optimal intervals to
      detect initial and subsequent VHL-related manifestations. In this study, we
      compare these results with the current VHL surveillance guidelines. We collected
      data from 82 VHL mutation carriers in the Dutch VHL surveillance program. The
      cumulative proportion of carriers diagnosed with a first VHL-related
      manifestation was estimated by the Kaplan-Meier method. The Poisson distribution
      model was used to calculate average time to detection of the first VHL-related
      manifestation and subsequent manifestations. We used this to calculate the
      optimal organ-specific age to initiate surveillance and the surveillance interval
      that results in a detection probability of 5%. The calculated organ-specific ages
      to initiate surveillance were 0 years (birth) for adrenal glands, 7 years for the
      retina, 14 years for the cerebellum, 15 years for the spinal cord, 16 years for
      pancreas, and 18 years for the kidneys. The calculated surveillance intervals
      were 4 years for the adrenal glands, biennially for the retina and pancreas, and
      annually for the cerebellum, spinal cord, and kidneys. Compared with current VHL
      guidelines, the calculated starting age of surveillance was 6 years later for the
      retina and 5 years earlier for adrenal glands. The surveillance intervals were
      two times longer for the retina and four times longer for the adrenal glands. To
      attain a 5% detection probability rate per organ, our mathematical model
      indicates that several modifications of current VHL surveillance guidelines
      should be considered. 

PMID- 24132473
TI  - Au103(SR)45, Au104(SR)45, Au104(SR)46 and Au105(SR)46 nanoclusters.
AB  - High resolution ESI mass spectrometry of the "22 kDa" nanocluster reveals the
      presence of a mixture containing Au103(SR)45, Au104(SR)45, Au104(SR)46, and
      Au105(SR)46 nanoclusters, where R = -CH2CH2Ph. MALDI TOF MS data confirm the
      purity of the sample and a UV-vis spectrum shows minor features.
      Au102(SC6H5COOH)44, whose XRD crystal structure was recently reported, is not
      observed. This is due to ligand effects, because the 102 : 44 composition is
      produced using aromatic ligands. However, the 103-, 104- and 105-atom
      nanoclusters, protected by -SCH2CH2Ph and -SC6H13 ligands, are at or near 58
      electron shell closing. 

PMID- 24132472
TI  - PPAR-gamma agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced
      neurotoxicity in primary neocortical cells.
AB  - Tetrabromobisphenol A (2,2-bis(4-hydroxy-3,5-dibromophenyl)propane; TBBPA) is a
      widely used brominated flame retardant. TBBPA induces neuronal damage, but the
      mechanism by which this occurs is largely unknown. We studied the possible
      involvement of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in
      TBBPA-induced apoptosis and toxicity in mouse primary neuronal cell cultures.
      TBBPA enhanced both, caspase-3 activity and lactate dehydrogenase (LDH) release
      in neocortical cells after 6 and 24 h of exposition. These data were supported at
      the cellular level with Hoechst 33342 staining. Immunoblot analyses showed that,
      compared with control cells, 10 MUM TBBPA decreased the expression of PPAR-gamma
      protein in neocortical neurons after 1-24 h of exposure. Co-treatment with TBBPA
      and GW1929 inhibited the TBBPA-induced caspase-3 activity, apoptotic body
      formation, and LDH release as well as TBBPA-induced decrease in PPAR-gamma
      protein expression. Thus, our data support neuroprotective potential of PPAR
      gamma agonists. The PPAR-gamma antagonist GW9662 prevented the TBBPA-induced
      decrease in PPAR-gamma protein level, but it potentiated TBBPA-induced apoptotic
      and neurotoxic effects, which suggest that the mechanism of TBBPA action in
      neuronal cells is not only PPAR-gamma-dependent. Therefore, further studies of
      the mechanism of TBBPA action in the nervous system are needed.

PMID- 24132474
TI  - Biophysical methods to monitor structural aspects of the adenovirus infectious
      cycle.
AB  - In this chapter we compile a battery of biophysical and imaging methods suitable
      to investigate adenovirus structural stability, structure, and assembly. Some are
      standard methods with a long history of use in virology, such as embedding and
      sectioning of infected cells, negative staining, or immunoelectron microscopy, as
      well as extrinsic fluorescence. The newer cryo-electron microscopy technique,
      which combined with advanced image processing tools has recently yielded an
      atomic resolution picture of the complete virion, is also described. Finally, we
      detail the procedure for imaging and interacting with single adenovirus virions
      using the atomic force microscope in liquid conditions. We provide examples of
      the kind of data obtained with each technique. 

PMID- 24132475
TI  - Proteome analysis of adenovirus using mass spectrometry.
AB  - Analysis of proteins and their posttranslational modifications is important for
      understanding different biological events. For analysis of viral proteomes, an
      optimal protocol includes production of a highly purified virus that can be
      investigated with a high-resolving analytical method. In this Methods in
      Molecular Biology paper we describe a working strategy for how structural
      proteins in the Adenovirus particle can be studied using liquid chromatography
      high-resolving mass spectrometry. This method provides information on the
      chemical composition of the virus particle. Further, knowledge about amino acids
      carrying modifications that could be essential for any part of the virus life
      cycle is collected. We describe in detail alternatives available for preparation
      of virus for proteome analysis as well as choice of mass spectrometric
      instrumentation suitable for this kind of analysis. 

PMID- 24132476
TI  - Capsid modification strategies for detargeting adenoviral vectors.
AB  - Adenoviral vectors hold immense potential for a wide variety of gene therapy
      based applications; however, their efficacy and toxicity is dictated by "off
      target" interactions that preclude cell specific targeting to sites of disease. A
      number of "off target" interactions have been described in the literature that
      occur between the three major capsid proteins (hexon, penton, and fiber) and
      components of the circulatory system, including cells such as erythrocytes, white
      blood cells, and platelets, as well as circulatory proteins including complement
      proteins, coagulation factors, von Willebrand Factor, p-selectin as well as
      neutralizing antibodies. Thus, to improve efficacious targeting to sites of
      disease and limit nonspecific uptake of virus to non-target tissues, specifically
      the liver and the spleen, it is necessary to develop suitable strategies for
      genetically modifying the capsid proteins to preclude these interactions. To this
      end we have developed versatile systems based on homologous recombination for
      modification of each of the major capsid proteins, which are described herein. 

PMID- 24132477
TI  - Use of dodecahedron "VLPs" as an alternative to the whole adenovirus.
AB  - During human adenovirus type 3 (Ad3) infection, an excess of penton base and
      fiber proteins are produced. These form dodecahedral particles composed of 12
      pentamers of penton base and 12 trimers of fiber protein. Beside this "natural"
      expression, the adenovirus dodecahedron can be expressed in the heterologous
      baculovirus system in two forms: a fiber-devoid dodecahedron made only of 12
      penton bases (called base-dodecahedron: Bs-Dd) and the fiber-containing
      dodecahedron (called penton dodecahedron: Pt-Dd). These particles partly mimic
      the adenoviral cellular entry pathway but are devoid of genetic information
      making them an unusual tool for basic research or applications. We report here
      how these particles are expressed and purified, the labeling method for
      trafficking studies as well as their use in molecular interaction studies. The
      potential of these particles for biotechnological applications is under
      evaluation, making their study a "niche" along side traditional adenoviral
      vectors. 

PMID- 24132478
TI  - Study of adenovirus and CAR axonal transport in primary neurons.
AB  - Vectors derived from the canine adenovirus serotype 2 (CAV-2) possess a high
      neurotropism and efficient retrograde transport that lead to widespread neuronal
      transduction in the central nervous system (CNS) of various animals. These
      abilities are due to the engagement of virions to the coxsackievirus and
      adenovirus receptor at the surface of neurons, which is linked to the endocytic
      and axonal transport machineries. The trafficking of CAV-2 and the coxsackievirus
      and adenovirus receptor (CAR) can be visualized ex vivo by incubating primary
      neurons (e.g., motoneurons and hippocampal neurons) with fluorescently labeled
      virions or recombinant viral proteins. Using this approach, we could recapitulate
      the mechanisms responsible for long-range transport of adenovirus in neurons. 

PMID- 24132479
TI  - The use of chromatin immunoprecipitation (ChIP) to study the binding of viral
      proteins to the adenovirus genome in vivo.
AB  - The encapsidation of adenovirus (Ad) DNA into virus particles depends on cis
      acting sequences located at the left end of the viral genome. Repeated DNA
      sequences in the packaging domain contribute to viral DNA encapsidation and
      several viral proteins bind to these repeats when analyzed using in vitro DNA
      protein binding assays. In this chapter, we describe a chromatin
      immunoprecipitation (ChIP) approach to study the binding of viral proteins to
      packaging sequences in vivo. This assay permits accurate quantification over a
      wide range of DNA concentrations. The use of formaldehyde cross-linking to
      stabilize DNA-protein and protein-protein complexes formed in vivo allows the
      identification of macromolecular complexes found in living cells. 

PMID- 24132480
TI  - DNA microarray to analyze adenovirus-host interactions.
AB  - Defining the molecular toxicity of viral vectors that are or will be in use for
      clinical trials is a prerequisite for their safe application in humans. DNA chips
      allow high-throughput evaluation of the profile of transduced cells and have
      contributed to underlining specific aspects of vector toxicity both in in vitro
      and in vivo assets. With gene chips we have been able to identify vector-specific
      properties, such as the cell cycle alteration induced by vector genomic DNA,
      along with the activation of specific innate immune pathways that can be ascribed
      to viral particles. We herein describe a detailed protocol for the use of gene
      chips to dissect the toxicogenomic signature of human and canine helper-dependent
      adenoviral vectors. We suggest specific procedures suited for the study of these
      viral vectors, but we also give indications that can be applied to different
      experimental contexts. In addition, we discuss the in silico elaboration of gene
      chip raw data which is a crucial step to extrapolate biological information from
      gene chip studies. 

PMID- 24132481
TI  - Determination of the transforming activities of adenovirus oncogenes.
AB  - The last 50 years of molecular biological investigations into human adenoviruses
      (Ads) have contributed enormously to our understanding of the basic principles of
      normal and malignant cell growth. Much of this knowledge stems from analyses of
      the Ad productive infection cycle in permissive host cells. Also, initial
      observations concerning the transforming potential of human Ads subsequently
      revealed decisive insights into the molecular mechanisms of the origins of cancer
      and established Ads as a model system for explaining virus-mediated
      transformation processes. Today it is well established that cell transformation
      by human Ads is a multistep process involving several gene products encoded in
      early transcription units 1A (E1A) and 1B (E1B). Moreover, a large body of
      evidence now indicates that alternative or additional mechanisms are engaged in
      Ad-mediated oncogenic transformation involving gene products encoded in early
      region 4 (E4) as well as epigenetic changes resulting from viral DNA integration.
      In particular, studies on the transforming potential of several E4 gene products
      have now revealed new pathways that point to novel general mechanisms of virus
      mediated oncogenesis. In this chapter we describe in vitro and in vivo assays to
      determine the transforming and oncogenic activities of the E1A, E1B, and E4
      oncoproteins in primary baby rat kidney cells, human amniotic fluid cells and
      athymic nude mice. 

PMID- 24132482
TI  - Oncolytic adenovirus characterization: activity and immune responses.
AB  - Virotherapy in one of the main current applications of recombinant adenoviruses.
      Oncolytic adenovirus are designed to target tumors, replicate selectively in
      tumor cells, and elicit immune responses against tumor antigens. Transgene
      expression in replication-competent oncolytic vectors allows to explore multiple
      strategies to enhance the potential of virotherapy. In this chapter we describe
      common in vivo and in vitro techniques used to evaluate the potency and
      biodistribution of oncolytic viruses. Monitoring immune responses against viral
      and tumor antigens is crucial as the immune system determines the outcome of
      virotherapy. 

PMID- 24132483
TI  - The analysis of innate immune response to adenovirus using antibody arrays.
AB  - Even though natural infections with adenovirus (Ad) are largely harmless in
      humans, an intravenous Ad vector administration for gene delivery purposes,
      especially at high doses, stimulates strong innate and adaptive immune responses,
      and can be fatal to the host. In animal models, intravenous Ad administration has
      been shown to induce transcription and release in the serum of a great number of
      pro-inflammatory cytokines and chemokines. Macrophages, including tissue
      residential macrophages (e.g., Kupffer cells in the liver), and dendritic cells
      throughout the body are considered to be the primary source of these pro
      inflammatory mediators following their transduction with Ads. Here, we provide an
      overview and methodology for the qualitative and quantitative analyses of pro
      inflammatory cytokine and chemokine expression in the spleen and their release
      into the bloodstream after intravenous Ad delivery using antibody arrays. 

PMID- 24132484
TI  - Engineering adenovirus genome by bacterial artificial chromosome (BAC)
      technology.
AB  - Bacterial artificial chromosomes (BACs) are recombinant DNA molecules designed
      for propagation of large and instable foreign DNA fragment in Escherichia coli.
      BACs are used in genetics of large DNA viruses such as herpes and baculoviruses
      for propagation and manipulation of complex genomic regions or even entire viral
      genomes in one piece. Viral genomes in BACs are ready for the advanced tools of
      E. coli genetics. These techniques based on homologous or site-specific
      recombination allow engineering of virtually any kind of genetic changes. In the
      recent years, BAC technology was also adapted to manipulation of adenovirus
      genomes and became an effective alternative to traditional genetic engineering of
      recombinant adenoviruses. 

PMID- 24132485
TI  - Construction, production, and purification of recombinant adenovirus vectors.
AB  - Recombinant adenoviruses provide a versatile system for gene expression studies
      and therapeutic applications. In this chapter, a standard procedure for their
      generation and small-scale production is described. Homologous recombination in
      E. coli between shuttle plasmids and full-length adenovirus backbones (E1
      deleted) is used for the generation of recombinant adenoviral vectors genomes.
      The adenovirus genomes are then analyzed to confirm their identity and integrity,
      and further linearized and transfected to generate a recombinant adenoviral
      vector in permissive human cells. These vectors are then purified by two
      sequential CsCl gradient centrifugations and subjected to a chromatography step
      in order to eliminate the CsCl and exchange buffers. Finally, the viral stock is
      characterized through the quantification of its viral particle content and its
      infectivity. 

PMID- 24132486
TI  - Scalable production of adenovirus vectors.
AB  - Recombinant adenoviruses (AdV) are highly efficient at gene transfer for a broad
      spectrum of cell types and species. They became one of the vectors of choice for
      gene delivery and expression of foreign proteins in gene therapy and vaccination
      purposes. To meet the need of significant amounts of adenoviral vectors for
      preclinical and possibly clinical uses, scalable and reproducible production
      processes are required.In this chapter, we review processes used for scalable
      production of two types of first generation (E1-deleted) adenoviral vectors
      (Human and Canine) using stirred tank bioreactors. The production of adenovirus
      vectors using either suspension (HEK 293) or anchorage-dependent cells (MDCK-E1)
      are described to exemplify scalable production processes with different cell
      culture types. The downstream processes will be covered in the next chapter. 

PMID- 24132487
TI  - Canine adenovirus downstream processing protocol.
AB  - Adenovirus vectors are efficient gene delivery tools. A major caveat with vectors
      derived from common human adenovirus serotypes is that most adults are likely to
      have been exposed to the wild-type virus and exhibit active immunity against the
      vectors. This preexisting immunity limits their clinical success. Strategies to
      circumvent this problem include the use of nonhuman adenovirus vectors. Vectors
      derived from canine adenovirus type 2 (CAV-2) are among the best-studied
      representatives. CAV-2 vectors are particularly attractive for the treatment of
      neurodegenerative disorders. In addition, CAV-2 vectors have shown great promise
      as oncolytic agents in virotherapy approaches and as vectors for recombinant
      vaccines. The rising interest in CAV-2 vectors calls for the development of
      scalable GMP compliant production and purification strategies. A detailed
      protocol describing a complete scalable downstream processing strategy for CAV-2
      vectors is reported here. Clarification of CAV-2 particles is achieved by
      microfiltration. CAV-2 particles are subsequently concentrated and partially
      purified by ultrafiltration-diafiltration. A Benzonase((r)) digestion step is
      carried out between ultrafiltration and diafiltration operations to eliminate
      contaminating nucleic acids. Chromatography purification is accomplished in two
      consecutive steps. CAV-2 particles are first captured and concentrated on a
      propyl hydrophobic interaction chromatography column followed by a polishing step
      using DEAE anion exchange monoliths. Using this protocol, high-quality CAV-2
      vector preparations containing low levels of contamination with empty viral
      capsids and other inactive vector forms are typically obtained. The complete
      process yield was estimated to be 38-45 %. 

PMID- 24132488
TI  - Production of high-capacity adenovirus vectors.
AB  - High-capacity adenoviral vectors (HC-Ad), also known as "helper-dependent" (HD
      Ad), "gutless", "gutted", or "third-generation" Ad vectors, are devoid of all
      viral coding sequences and have shown promising potential for a wide variety of
      different applications-from classic gene therapy to genetic vaccination and tumor
      treatment. However, compared to first-generation adenoviral vectors their
      production is more complex and requires specific in-depth knowledge. This chapter
      delivers a detailed protocol for the successful production of HC-Ad vectors to
      high titers. 

PMID- 24132489
TI  - Production of chimeric adenovirus.
AB  - The use of chimeric pseudotyped vectors is a common way to modify the adenoviral
      tropism by replacing the fiber protein. In this chapter the procedure to generate
      a chimeric adenovirus pre-stock from a plasmid containing the adenoviral genome
      is described. Also, the chimeric adenovirus replicative cycle to increase the
      yield in further productions is determined. Finally, two different protocols, in
      culture plates and in suspension cultures, to produce the virus at large scale
      are also detailed. 

PMID- 24132490
TI  - Incorporating variability in honey bee waggle dance decoding improves the mapping
      of communicated resource locations.
AB  - Honey bees communicate to nestmates locations of resources, including food,
      water, tree resin and nest sites, by making waggle dances. Dances are composed of
      repeated waggle runs, which encode the distance and direction vector from the
      hive or swarm to the resource. Distance is encoded in the duration of the waggle
      run, and direction is encoded in the angle of the dancer's body relative to
      vertical. Glass-walled observation hives enable researchers to observe or video,
      and decode waggle runs. However, variation in these signals makes it impossible
      to determine exact locations advertised. We present a Bayesian duration to
      distance calibration curve using Markov Chain Monte Carlo simulations that allows
      us to quantify how accurately distance to a food resource can be predicted from
      waggle run durations within a single dance. An angular calibration shows that
      angular precision does not change over distance, resulting in spatial scatter
      proportional to distance. We demonstrate how to combine distance and direction to
      produce a spatial probability distribution of the resource location advertised by
      the dance. Finally, we show how to map honey bee foraging and discuss how our
      approach can be integrated with Geographic Information Systems to better
      understand honey bee foraging ecology. 

PMID- 24132491
TI  - Memory loss: do not forget the mammillary bodies.

PMID- 24132492
TI  - Usefulness of ultrasonography in posterior reversible encephalopathy syndrome.

PMID- 24132493
TI  - Repeated botulinum toxin type A (Dysport) injections for women with intractable
      detrusor overactivity: a prospective outcome study.
AB  - INTRODUCTION AND HYPOTHESIS: We present the cohort of 33 women who underwent
      botulinum toxin type A (BTX-A) injections examining the efficacy and safety of
      BTX-A in idiopathic detrusor overactivity (IDO). The aim of this report is to
      describe the outcomes of those who underwent repeated injections of BTX-A.
      METHODS: All 33 women had 3 or more injections with an initial dose of 500 units
      of Dysport with subsequent injections between 500 and 750 U, administered by the
      classic trigone-sparing flexible/rigid cystoscopic technique. An informed consent
      was obtained in all cases. Efficacy was measured using voiding diaries and
      quality of life (QOL) assessed with the International Consultation on
      Incontinence Questionnaire-Short Form (ICIQ -SF). This project was approved by
      the Clinical Effectiveness Department and the Drugs and Therapeutics Committee
      (DTC). Therefore, ethical approval was not required. RESULTS: This study included
      33 women who have been successfully treated with repeated intradetrusor
      injections of BTX-A (Dysport). Mean duration between the first and second
      injections was 15.2 +/- 7.2 months, whereas between the second and third was 19.2
      +/- 10 months (P = 0.025). Two women developed urinary tract infection and
      required clean intermittent self-catheterization. Three women required dose
      escalation to 750 units. Longer duration of subjective QOL improvement was noted
      between the second and third botulinum toxin injections compared to duration
      between the first and second injections. CONCLUSIONS: BTX-A appears to be
      effective and safe after repeated administration in women with IDO. The duration
      of the injection tends to get prolonged after the second injection.

PMID- 24132494
TI  - Transvaginal removal of mesh exposure involving the bladder.
AB  - INTRODUCTION AND HYPOTHESIS: We present three cases of transvaginal removal of
      mesh exposure involving the bladder, including patient follow-up. Mesh exposure
      occurred secondary to placement of transvaginal mesh for management of pelvic
      organ prolapse. METHODS: A pure transvaginal technique was performed to remove
      mesh exposure involving the bladder. Patient follow-ups were carefully recorded.
      RESULTS: All operative steps were completed transvaginally. The duration of
      follow-up for the three cases was 6, 11, and 19 months. One patient experienced
      recurrence of mesh exposure during follow-up. The other two patients were symptom
      free after surgery. There were no major postoperative complications and no
      recurrence of cystocele. CONCLUSIONS: Transvaginal removal of mesh exposure
      involving the bladder is feasible. The pure transvaginal approach is applicable
      to various conditions with good outcomes, yet it cannot guarantee that exposure
      of residual fibers within the bladder will not recur.

PMID- 24132496
TI  - Biodegradation of a mixture of PAHs by non-ligninolytic fungal strains isolated
      from crude oil-contaminated soil.
AB  - Nine native non-ligninolytic fungal strains were isolated from Maya crude oil
      contaminated soil and selected based on their ability to grow and use crude oil
      and several polycyclic aromatic hydrocarbons (PAHs) as carbon source, for their
      application to PAH removal in soil. The fungi were identified by PCR
      amplification of intergenic transcribed sequences regions and microbiological
      techniques, and results showed them to be part of the genera Fusarium,
      Neurospora, Aspergillus, Scedosporium, Penicillium, Neosartorya and Talaromyces.
      A primary selection of fungi was made in minimal medium plates, considering the
      tolerance to different concentrations of PAHs for each strain. The radial
      extension rate exhibited significant differences (p < 0.05) from 200 to 1,000 mg
      of PAHs mixture l-1. A secondary selection of Aspergillus terreus, Talaromyces
      spectabilis, and Fusarium sp. was achieved based on their tolerance to 2,000 mg
      of a mixture of Phenanathrene and Pyrene kg-1 of soil in a solid-state microcosm
      system for 2 weeks. The percentage of PAH removal obtained by the three strains
      was approximately 21 % of the mixture.

PMID- 24132497
TI  - Myrtucommulone production by a strain of Neofusicoccum australe endophytic in
      myrtle (Myrtus communis).
AB  - Myrtucommulones are acylphloroglucinol compounds reported from myrtle (Myrtus
      communis) and a few more plant species belonging in the Myrtaceae that have
      recently attracted the attention of pharmacologists for their anti-oxidant, anti
      inflammatory and anti-tumor properties. An endophytic strain of Neofusicoccum
      australe recovered from a myrtle branch was selected based on the bioactivity of
      its culture extracts, and found to produce myrtucommulones A and D. A mixture of
      these compounds induced anti-proliferative effects on the human prostatic cancer
      cell lines DU145 and PC3, with a IC50 of respectively 4.64 and 3.11 mg/l. Along
      the lines of recent evidences of the ability by endophytic fungi to produce
      bioactive compounds originally extracted from their host plants, this is the
      first report of myrtucommulones as secondary metabolites of an endophytic fungal
      strain. The availability of a microbial strain to be cultured in vitro may
      provide access to more substantial amounts of these products for further
      investigations in view of their possible pharmaceutical use.

PMID- 24132498
TI  - Suppression of proliferation and migration in highly-metastatic lung cancer cells
      as well as tumor growth by a new synthesized compound TBrC and its molecular
      mechanisms of action.
AB  - To develop new anticancer agents has been considered as a useful and necessary
      strategy to suppress highly-metastatic lung cancer, the leading cause of cancer
      related deaths in the world. In this study, we synthesized a new compound ethyl 6
      bromocoumarin-3-carboxylyl L-theanine (TBrC) and studied the anticancer activity
      of TBrC and its molecular mechanisms of action. Our results show that TBrC
      remarkably inhibits the proliferation and migration in highly-metastatic lung
      cancer cells by inducing apoptosis and cell cycle arrest as well as regulating
      related protein expressions. Further study indicated that TBrC not only enhances
      the protein levels of Bax, cytosolic cytochrome c, caspase-3 and PARP-1 but also
      reduces the protein expressions of Bcl-2, cyclin D1, VEGFR1 and NF-kappaB as well
      as inhibits the phosphorylation and expressions of VEGFR2 and Akt in the cancer
      cells. More importantly, TBrC displays strong suppression of highly-metastatic
      tumor growth and reduces the tumor weight by 61.6 % in tumor-bearing mice without
      toxicity to the mice. Our results suggest that TBrC suppresses the proliferation
      and migration of lung cancer cells via VEGFR-Akt-NF-kappaB signaling pathways;
      TBrC may have a wide therapeutic and/or adjuvant therapeutic application in the
      treatment of lung cancer. 

PMID- 24132499
TI  - Decrease in insulin resistance has a key role in improvement of metabolic profile
      during intragastric balloon treatment.

PMID- 24132500
TI  - Health, job characteristics, skills, and social and financial factors in relation
      to early retirement--results from a longitudinal study in the Netherlands.
AB  - OBJECTIVES: This study aimed to investigate the relative contribution of health,
      job characteristics, skills and knowledge, and social and financial factors to
      the transition from work to (non-disability) early retirement. METHODS: Employees
      aged 59-63 years (N=2317) were selected from the Study on Transitions in
      Employment, Ability and Motivation in the Netherlands (STREAM). Individual
      characteristics, health, job characteristics, skills and knowledge, and social
      and financial factors were measured using a questionnaire at baseline.
      Information on early retirement was derived from the one-year follow-up
      questionnaire. Logistic regression analyses were used to identify predictors of
      early retirement. Population Attributable Fractions (PAF) were calculated.
      RESULTS: Older age [odds ratio (OR) 1.79], poor physical health (OR 1.78), a
      positive attitude of the partner with respect to early retirement (OR 3.85), and
      the financial possibility to stop working before the age of 65 (OR 10.2)
      predicted the transition to early retirement, whereas employees that reported
      high appreciation at work (OR 0.58) and higher focus on development of skills and
      knowledge (OR 0.54) were less likely to retire early. PAF were 0.75 for the
      financial possibility to stop working, 0.43 for a positive attitude of the
      partner with respect to early retirement, 0.27 for low appreciation at work, 0.23
      for a low focus on development, and 0.21 for poor health. CONCLUSIONS: The
      financial possibility to stop working before the age of 65 importantly
      contributes to early retirement. In the context of rapidly diminishing financial
      opportunities to retire early in the Netherlands, the prolongation of working
      life might be promoted by workplace health promotion and disability management,
      and work-related interventions focusing on appreciation and the learning
      environment.

PMID- 24132501
TI  - Why and when is ethnic harassment a risk for immigrant adolescents' school
      adjustment? understanding the processes and conditions.
AB  - Ethnically harassed immigrant youth are at risk for experiencing a wide range of
      school adjustment problems. However, it is still unclear why and under what
      conditions experiencing ethnic harassment leads to school adjustment
      difficulties. To address this limitation in the literature, we examined two
      important questions. First, we investigated whether self-esteem and/or depressive
      symptoms would mediate the associations between ethnic harassment and poor school
      adjustment among immigrant youth. Second, we examined whether immigrant youths'
      perception of school context would play a buffering role in the pathways between
      ethnic harassment and school adjustment difficulties. The sample (n = 330; M age
      = 14.07, SD = .90; 49% girls at T1) was drawn from a longitudinal study in
      Sweden. The results revealed that experiencing ethnic harassment led to a
      decrease in immigrant youths' self-esteem over time, and that youths'
      expectations of academic failure increased. Further, youths' relationships with
      their teachers and their perceptions of school democracy moderated the mediation
      processes. Specifically, when youth had poor relationships with their teachers or
      perceived their school context as less democratic, being exposed to ethnic
      harassment led to a decrease in their self-esteem. In turn, they reported low
      school satisfaction and perceived themselves as being unsuccessful in school.
      Such indirect effects were not observed when youth had high positive
      relationships with their teachers or perceived their school as offering a
      democratic environment. These findings highlight the importance of understanding
      underlying processes and conditions in the examination of the effects of ethnic
      devaluation experiences in order to reach a more comprehensive understanding of
      immigrant youths' school adjustment.

PMID- 24132502
TI  - Localised intraspecific variation in the swimming phenotype of a coral reef fish
      across different wave exposures.
AB  - Wave-driven water flow is a major force structuring marine communities. Species
      distributions are partly determined by the ability to cope with variation in
      water flow, such as differences in the assemblage of fish species found in a
      given water flow environment being linked to swimming ability (based on fin shape
      and mode of locomotion). It remains unclear, however, whether similar assembly
      rules apply within a species. Here we show phenotypic variation among sites in
      traits functionally linked to swimming ability in the damselfish Acanthochromis
      polyacanthus. These sites differ in wave energy and the observed patterns of
      phenotypic differences within A. polyacanthus closely mirrored those seen at the
      interspecific level. Fish from high-exposure sites had more tapered fins and
      higher maximum metabolic rates than conspecifics from sheltered sites. This
      translates to a 36% larger aerobic scope and 33% faster critical swimming speed
      for fish from exposed sites. Our results suggest that functional relationships
      among swimming phenotypes and water flow not only structure species assemblages,
      but can also shape patterns of phenotypic divergence within species. Close links
      between locomotor phenotype and local water flow conditions appear to be
      important for species distributions as well as phenotypic divergence across
      environmental gradients.

PMID- 24132503
TI  - Wintering birds avoid warm sunshine: predation and the costs of foraging in
      sunlight.
AB  - Wintering birds can gain significant thermal benefits by foraging in direct
      sunlight. However, exposure to bright sunlight might make birds easier to detect
      by predators and may also cause visual glare that can reduce a bird's ability to
      monitor the environment. Thus, birds likely experience a trade-off between the
      thermal benefits and predation-related costs of foraging in direct sunlight. To
      examine this possible thermoregulation-predation trade-off, we monitored the
      behavior of mixed-species flocks of wintering emberizid sparrows foraging in
      alternating strips of sunlight and shade. On average, these sparrows routinely
      preferred to forage in the shade, despite midday air temperatures as much as 30 
      degrees C below their thermoneutral zone. This preference for shade was strongest
      at relatively high temperatures when the thermal benefits of foraging in sunlight
      were reduced, suggesting a thermoregulation-predation trade-off. Glare could be
      reduced if birds faced away from the sun while feeding in direct sunlight, but we
      found that foraging birds tended to face southward (the direction of the sun). We
      speculate that other factors, such as the likely direction of predator approach,
      may explain this southerly orientation, particularly if predators use solar glare
      to their advantage during an attack. This interpretation is supported by the fact
      that birds had the weakest southerly orientation on cloudy days. Wintering birds
      may generally avoid foraging in direct sunlight to minimize their risk of
      predation. However, given the thermal benefits of sunshine, such birds may
      benefit from foraging in habitats that provide a mosaic of sunlit and shaded
      microhabitats.

PMID- 24132504
TI  - The New Zealand new psychoactive substances regime--a step in the right
      direction, but questions still remain.

PMID- 24132505
TI  - Reply to Sumnall (2013), 'The New Zealand new psychoactive substances regime--a
      step in the right direction, but questions still remain'.

PMID- 24132506
TI  - 'A dancing ball in the heart': false tendon of the left ventricle simulating a
      mass lesion.

PMID- 24132507
TI  - Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting
      glycogen synthase kinase-3beta activation in human liver cells.
AB  - BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte
      lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The
      purpose of this study was to investigate saturated fatty acid induction of
      lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human
      liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty
      acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase
      3beta (GSK-3beta) inhibitor, or GSK-3beta shRNA transfection. Transmission
      electron microscopy was used to detect morphological changes, flow cytometry was
      used to detect apoptosis, a colorimetric assay was used to detect caspase-3
      activity, and western blot analysis was used to detect protein expression.
      RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis
      in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate
      activated GSK-3beta protein, which was indicated by dephosphorylation of GSK
      3beta at Ser-9. However, inhibition of GSK-3beta activity with lithium chloride
      treatment or knockdown of GSK-3beta expression with shRNA suppressed sodium
      palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level,
      inhibition of GSK-3beta expression or activity suppressed sodium palmitate
      induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation,
      whereas GSK-3beta inhibition did not affect endoplasmic reticulum stress-induced
      activation of unfolded protein response. CONCLUSIONS: The present data
      demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in
      human liver L02 and HepG2 cells was regulated by GSK-3beta activation, which led
      to JNK activation and Bax upregulation. This finding indicates that GSK-3beta
      inhibition may be a potential therapeutic target to control NAFLD.

PMID- 24132508
TI  - Modulation of nitrergic signalling pathway by American ginseng attenuates chronic
      unpredictable stress-induced cognitive impairment, neuroinflammation, and
      biochemical alterations.
AB  - Prolonged stress causes extensive loss of neurons leading to deficits in
      cognitive performance. Increasing evidence indicates that accumulation of
      intercellular messenger, nitric oxide (NO), plays a crucial role in the
      pathogenesis of memory disorders. American ginseng (AG) is known to show
      protection in different animal models of neurological diseases; however, its
      exact mechanism of action is not clearly understood. Therefore, the current study
      was designed to investigate the interaction of AG against chronic unpredictable
      stress (CUS)-associated behavioral and biochemical alterations and the probable
      role of nitrergic pathway in this effect. Male Laca mice were exposed to a series
      of stressors along with drug/vehicle treatment daily for 28 days. CUS paradigm
      caused significant impairment in both acquisition and retention memory as
      measured in Morris water maze and elevated plus maze task. This was coupled with
      alterations in oxidative stress markers, mitochondrial enzyme complex activities,
      pro-inflammatory cytokine (TNF-alpha), and acetylcholinesterase levels in the
      hippocampus as compared with naive group. Besides, there was a marked increase in
      serum corticosterone levels. AG (100, 200 mg/kg; p.o.) treatment significantly
      improved cognitive impairment; reduced TNF-alpha, acetylcholinesterase, and
      corticosterone levels; and attenuated oxidative-nitrergic stress. Furthermore,
      pre-treatment of L-arginine (100 mg/kg; i.p.), a nitric oxide donor, with
      subeffective dose of AG (100 mg/kg; p.o.) reversed its protective effects.
      However, L-NAME (10 mg/kg, i.p.), a non-specific NO synthase inhibitor,
      potentiated the effects of AG. Our findings suggest that modulation of nitrergic
      signalling cascade is involved in the protective effects of AG against CUS
      induced cognitive dysfunction, oxidative stress, and neuroinflammation. 

PMID- 24132509
TI  - Phylogenetic analysis of HCV-4d in Turkey: the curious case of Kayseri province.
AB  - In Turkey, genotype 1, especially type 1b virus, causes approximately 90% of
      these infections, while types 2, 3, and 4 exist, albeit in low prevalences and
      are due to relatively recent and limited introductions. Two recent reports from
      Kayseri, a relatively large city in Central Anatolia, indicated unusually high
      prevalence for type 4 infections in the province reaching a 35% among patients
      admitted to hospitals for treatment of chronic hepatitis C. In this study, the
      origin, the demographic history, and the dynamic of the epidemic of unusual HCV
      genotype 4d in Turkey by using Bayesian coalescent-based method were
      investigated. A gene flow migration approach was also used to describe the
      synchronous geographical dispersal and genetic diversification of this unusual
      genotype in Kayseri province. The Turkish clade had a tMRCA of 44 years
      corresponding to the year 1967 and seems to have a different origin being
      completely segregated from the European one. Gene flow migration analysis
      indicated that Kayseri province appeared to be the epicenter of HCV-4d epidemic,
      exporting the infections. The demographic history of HCV-4d showed that the
      epidemic started in 1970s year then following a slow exponential growth until
      1980s. The Turkish monophyletic clade suggests a segregate circulation of the
      epidemic in this region mostly due to unsafe parenteral medical procedures (with
      drug addiction playing a relatively negligible role).

PMID- 24132510
TI  - Influence of bacteria on epigenetic gene control.
AB  - Cellular information is inherited by daughter cells through epigenetic routes in
      addition to genetic routes. Epigenetics, which is primarily mediated by
      inheritable DNA methylation and histone post-translational modifications,
      involves changes in the chromatin structure important for regulating gene
      expression. It is widely known that epigenetic control of gene expression plays
      an essential role in cell differentiation processes in vertebrates. Furthermore,
      because epigenetic changes can occur reversibly depending on environmental
      factors in differentiated cells, they have recently attracted considerable
      attention as targets for disease prevention and treatment. These environmental
      factors include diet, exposure to bacteria or viruses, and air pollution, of
      which this review focuses on the influence of bacteria on epigenetic gene control
      in a host. Host-bacterial interactions not only occur upon pathogenic bacterial
      infection but also continuously exist between commensal bacteria and the host.
      These bacterial stimuli play an essential role in various biological responses
      involving external stimuli and in maintaining physiological homeostasis by
      altering epigenetic markers and machinery. 

PMID- 24132512
TI  - Titanium dioxide nanoparticles affect the growth and microRNA expression of
      tobacco (Nicotiana tabacum).
AB  - Titanium dioxide (TiO(2)) is one of the most widely used pigments in the world.
      Due to its heavy use in industry and daily life, such as food additives,
      cosmetics, pharmaceuticals, and paints, many residues are released into the
      environment and currently TiO(2) nanoparticles are considered an emerging
      environmental contaminant. Although several studies have shown the effect of
      TiO(2) nanoparticles on a wide range of organisms including bacteria, algae,
      plankton, fish, mice, and rats, little research has been performed on land
      plants. In this study, we investigated the effect of TiO(2) nanoparticles on the
      growth, development, and gene expression of tobacco, an important economic and
      agricultural crop in the southeastern USA as well as around the world. We found
      that TiO(2) nanoparticles significantly inhibited the germination rates, root
      lengths, and biomasses of tobacco seedlings after 3 weeks of exposure to 0.1, 1,
      2.5, and 5 % TiO(2) nanoparticles and that overall growth and development of the
      tobacco seedlings significantly decreased as TiO(2) nanoparticle concentrations
      increased. Overall, tobacco roots were the most sensitive to TiO(2) nanoparticle
      exposure. Nano-TiO(2) also significantly influenced the expression profiles of
      microRNAs (miRNAs), a recently discovered class of small endogenous noncoding
      RNAs (~20-22 nt) that are considered important gene regulators and have been
      shown to play an important role in plant development as well as plant tolerance
      to abiotic stresses such as drought, salinity, cold, and heavy metal. Low
      concentrations (0.1 and 1 %) of TiO(2) nanoparticles dramatically induced miRNA
      expression in tobacco seedlings with miR395 and miR399 exhibiting the greatest
      fold changes of 285-fold and 143-fold, respectively. The results of this study
      show that TiO(2) nanoparticles have a negative impact on tobacco growth and
      development and that miRNAs may play an important role in tobacco response to
      heavy metals/nanoparticles by regulating gene expression.

PMID- 24132511
TI  - Crosstalk between cerebral endothelium and oligodendrocyte.
AB  - It is now relatively well accepted that the cerebrovascular system does not
      merely provide inert pipes for blood delivery to the brain. Cerebral endothelial
      cells may compose an embedded bunker of trophic factors that contribute to brain
      homeostasis and function. Recent findings suggest that soluble factors from
      cerebral endothelial cells nourish neighboring cells, such as neurons and
      astrocytes. Although data are strongest in supporting mechanisms of endothelial
      neuron and/or endothelial-astrocyte trophic coupling, it is likely that similar
      interactions also exist between cerebral endothelial cells and oligodendrocyte
      lineage cells. In this mini-review, we summarize current advances in the field of
      endothelial-oligodendrocyte trophic coupling. These endothelial-oligodendrocyte
      interactions may comprise the oligovascular niche to maintain their cellular
      functions and sustain ongoing angiogenesis/oligodendrogenesis. Importantly, it
      should be noted that the cell-cell interactions are not static-the trophic
      coupling is disturbed under acute phase after brain injury, but would be
      recovered in the chronic phase to promote brain remodeling and repair.
      Oligodendrocyte lineage cells play critical roles in white matter function, and
      under pathological conditions, oligodendrocyte dysfunction lead to white matter
      damage. Therefore, a deeper understanding of the mechanisms of endothelial
      oligodendrocyte trophic coupling may lead to new therapeutic approaches for white
      matter-related diseases, such as stroke or vascular dementia. 

PMID- 24132514
TI  - Let's talk about sex and endometriosis.

PMID- 24132513
TI  - Horizontal gene transfer in plants.
AB  - Horizontal gene transfer (HGT) describes the transmission of genetic material
      across species boundaries. HGT often occurs in microbic and eukaryotic genomes.
      However, the pathways by which HGTs occur in multicellular eukaryotes, especially
      in plants, are not well understood. We systematically summarized more than ten
      possible pathways for HGT. The intimate contact which frequently occurs in
      parasitism, symbiosis, pathogen, epiphyte, entophyte, and grafting interactions
      could promote HGTs between two species. Besides these direct transfer methods,
      genes can be exchanged with a vector as a bridge: possible vectors include
      pollen, fungi, bacteria, viruses, viroids, plasmids, transposons, and insects.
      HGT, especially when involving horizontal transfer of transposable elements, is
      recognized as a significant force propelling genomic variation and biological
      innovation, playing an important functional and evolutionary role in both
      eukaryotic and prokaryotic genomes. We proposed possible mechanisms by which HGTs
      can occur, which is useful in understanding the genetic information exchange
      among distant species or distant cellular components. 

PMID- 24132515
TI  - Caged nucleotides/nucleosides and their photochemical biology.
AB  - Nucleotides and nucleosides are not only key units of DNA/RNA that store genetic
      information, but are also the regulators of many biological events of our lives.
      By caging the key functional groups or key residues of nucleotides with
      photosensitive moieties, it will be possible to trigger biological events of
      target nucleotides with spatiotemporal resolution and amplitude upon light
      activation or photomodulate polymerase reactions with the caged nucleotide
      analogues for next-generation sequencing (NGS) and bioorthogonal labeling. This
      review highlights three different caging strategies for nucleotides and
      demonstrates the photochemical biology of these caged nucleotides. 

PMID- 24132516
TI  - Presentation, pathology, and treatment outcome of brain tumors in 172 consecutive
      children at CURE Children's Hospital of Uganda. The predominance of the visible
      diagnosis and the uncertainties of epidemiology in sub-Saharan Africa.
AB  - OBJECT: This study reviews the first operative series of pediatric brain tumors
      from Uganda, the largest series from Sub-Saharan Africa, and explores the
      challenges to progress in pediatric neuro-oncology in the region. METHODS: This
      is a retrospective operative series of brain tumors in 172 children at Cure
      Children's Hospital of Uganda over 10 years. Demographics, clinical presentation,
      lesion location, histopathology, operative management, and outcome were
      investigated. Survival was assessed using Kaplan-Meier method. Log-rank test and
      p value with Bonferroni correction were used to determine significance of
      survival differences. RESULTS: There were 103 males (59.9 %) and 69 females (40.1
      %; mean age at diagnosis 6.5 years with 29 % < 2 years). The most common
      histologic types were pilocytic astrocytoma (23.2 %), ependymoma (16.3 %),
      craniopharyngioma (9.9 %), choroid plexus papilloma (9.3 %), and medulloblastoma
      (8.1 %). Supratentorial tumors (62.2 %) were more common. Symptomatic
      hydrocephalus predominated at presentation (66.9 %). In 71 (41.3 %), the
      presentation was macrocephaly or a visible mass. Estimated 5-year survival was 60
      %. CONCLUSIONS: The majority of pediatric brain tumors in the region likely go
      unrecognized. Most that do come to attention have a "visible diagnosis." Unlike
      operative series from developed countries, information about the incidence,
      prevalence, and overall burden of disease for different tumor types cannot be
      deduced from the various operative series reported from limited resource
      countries because of the selection bias that is unique to this context. Delayed
      presentation and poor access to adjuvant therapies were important contributors to
      the high mortality. The epidemiology of pediatric brain tumors in sub-Saharan
      Africa is obscure.

PMID- 24132517
TI  - The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic
      nephropathy in Chinese patients with type 2 diabetes mellitus.
AB  - The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with
      obesity, reduced glucose-induced insulin secretion in healthy or diabetic
      subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We
      evaluated the association of the Leu72Met polymorphism with measures of insulin
      sensitivity in non-diabetic control individuals and type 2 diabetics, and whether
      this variation contributes to the development of diabetic nephropathy (DN) in
      type 2 diabetes. A case-control study was performed of 291 non-diabetic control
      subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt
      albuminuria (DN group; albuminuric excretion rate [AER] >= 300 mg/24 h) and 228
      did not have DN, but had diabetes for more than 10 years (non-DN group).
      Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and
      Met/Met genotype frequencies were significantly different between the non-DN and
      DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met)
      was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p
      = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and
      higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and
      Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher
      eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met
      polymorphism may help to maintain normal renal function and may protect against
      the development of DN by reducing albuminuria and improving renal function in
      Chinese patients with type 2 diabetes.

PMID- 24132518
TI  - Non-scarring patchy alopecia in patients with systemic lupus erythematosus
      differs from that of alopecia areata.
AB  - BACKGROUND: Non-scaring patchy alopecia associated with systematic lupus
      erythematosus (SLE) is sometimes mis-diagnosed as alopecia areata (AA).
      OBJECTIVES: Our aim was to differentiate non-scarring patchy SLE alopecia
      features from patchy AA. METHODS: Clinical, dermatoscopic and histopathological
      data from 21 SLE patients with patchy alopecia were compared with data from 21
      patients with patchy AA. RESULTS: Incomplete alopecia was common in SLE alopecia
      patches, while AA patches exhibited complete alopecia. Exclamation-mark hairs,
      black dots, broken hair and yellow dots were common to AA, while hair shaft
      thinning and hypopigmentation, angiotelectasis, peripilar sign, perifollicular
      red dots, white dots and honeycomb pigment patterns were more common in SLE.
      Interfollicular polymorphous vessels were the most common angiotelectasis
      presentation in the SLE alopecia patches, but interfollicular arborizing vessels
      were significantly more common in non-hair-loss-affected SLE regions and in AA
      hair-loss regions. During follow-up, increased vellus hair was the earliest
      feature that emerged after treatment both in SLE and AA, while the earliest
      feature that disappeared was hair shaft hypopigmentation in SLE and broken hair
      in AA. After treatment, no SLE patients had relapse of alopecia, while 41.7% of
      AA patients did. CONCLUSION: Distinct clinical, dermatoscopic and
      histopathological features were found in SLE-associated alopecia regions, which
      were different from those of AA. Serological autoantibody tests are of value to
      confirm the differential diagnosis. Local angiotelectasis and vasculitis close to
      hair follicles may be involved in the pathogenesis of alopecia in SLE.

PMID- 24132520
TI  - Ustekinumab associated with flares of psoriatic arthritis.
AB  - IMPORTANCE: Ustekinumab is a human monoclonal antibody that binds to the shared
      p40 subunit of interleukin (IL) 12 and IL-23. It is approved in the United States
      for adults (>18 years) with moderate to severe plaque psoriasis who are
      candidates for phototherapy or systemic therapy. In 1 phase 2 trial of
      ustekinumab for treatment of psoriatic arthritis, joint disease improved.
      OBSERVATION: We report 4 cases of ustekinumab monotherapy for plaque psoriasis
      that resulted in disabling flares of known psoriatic arthritis or unmasked
      previously occult joint disease. In all of our cases, psoriasis improved
      dramatically with ustekinumab therapy while psoriatic arthritis flared.
      CONCLUSIONS AND RELEVANCE: Despite early results of a phase 2 ustekinumab trial
      suggesting efficacy for both plaque psoriasis and psoriatic arthritis, our case
      series raises concern that ustekinumab may unmask or aggravate joint disease in
      selected patients. These data underscore the need for further investigation of
      ustekinumab's effects on psoriatic arthritis.

PMID- 24132519
TI  - Complete republication: National Association of Medical Examiners position paper:
      Recommendations for the investigation, diagnosis, and certification of deaths
      related to opioid drugs.
AB  - The American College of Medical Toxicology and the National Association of
      Medical Examiners convened an expert panel to generate evidence-based
      recommendations for the practice of death investigation and autopsy,
      toxicological analysis, interpretation of toxicology findings, and death
      certification to improve the precision of death certificate data available for
      public health surveillance. The panel finds the following: 1. A complete autopsy
      is necessary for optimal interpretation of toxicology results, which must also be
      considered in the context of the circumstances surrounding death, medical
      history, and scene findings. 2. A complete scene investigation extends to
      reconciliation of prescription information and pill counts. 3. Blood, urine, and
      vitreous humor, when available, should be retained in all cases. Blood from the
      femoral vein is preferable to blood from other sites. 4. A toxicological panel
      should be comprehensive and include opioid and benzodiazepine analytes, as well
      as other potent depressant, stimulant, and anti-depressant medications. 5.
      Interpretation of postmortem opioid concentrations requires correlation with
      medical history, scene investigation, and autopsy findings. 6. If death is
      attributed to any drug or combination of drugs (whether as cause or contributing
      factor), the certifier should list all the responsible substances by generic name
      in the autopsy report and on the death certificate. 7. The best classification
      for manner of death in deaths due to the misuse or abuse of opioids without any
      apparent intent of self-harm is "accident." Reserve "undetermined" as the manner
      for the rare cases in which evidence exists to support more than one possible
      determination.

PMID- 24132521
TI  - COP-compost: a software to study the degradation of organic pollutants in
      composts.
AB  - Composting has been demonstrated to be effective in degrading organic pollutants
      (OP) whose behaviour depends on the composting conditions, the microbial
      populations activated and interactions with organic matters. The fate of OP
      during composting involves complex mechanisms and models can be helpful tools for
      educational and scientific purposes, as well as for industrialists who want to
      optimise the composting process for OP elimination. A COP-Compost model, which
      couples an organic carbon (OC) module and an organic pollutant (OP) module and
      which simulates the changes of organic matter, organic pollutants and the
      microbial activities during the composting process, has been proposed and
      calibrated for a first set of OP in a previous study. The objectives of the
      present work were (1) to introduce the COP-Compost model from its convenient
      interface to a potential panel of users, (2) to show the variety of OP that could
      be simulated, including the possibility of choosing between degradation through
      co-metabolism or specific metabolism and (3) to show the effect of the initial
      characteristics of organic matter quality and its microbial biomass on the
      simulated results of the OP dynamic. In the model, we assumed that the pollutants
      can be adsorbed on organic matter according to the biochemical quality of the OC
      and that the microorganisms can degrade the pollutants at the same time as they
      degrade OC (by co-metabolism). A composting experiment describing two different
      (14)C-labelled organic pollutants, simazine and pyrene, were chosen from the
      literature because the four OP fractions simulated in the model were measured
      during the study (the mineralised, soluble, sorbed and non-extractable
      fractions). Except for the mineralised fraction of simazine, a good agreement was
      achieved between the simulated and experimental results describing the evolution
      of the different organic fractions. For simazine, a specific biomass had to be
      added. To assess the relative importance of organic matter dynamics on the
      organic pollutants' behaviour, a sensitivity analysis was conducted. The
      sensitivity analysis demonstrated that the parameters associated with organic
      matter dynamics and its initial microbial biomass greatly influenced the
      evolution of all the OP fractions, although the initial biochemical quality of
      the OC did not have a significant impact on the OP evolution. 

PMID- 24132522
TI  - Tolerance to iron accumulation and its effects on mineral composition and growth
      of two grass species.
AB  - This study aimed to assess the influence of excess iron on the capacity of
      accumulation of this heavy metal, mineral composition, and growth of Setaria
      parviflora and Paspalum urvillei. Seedlings were submitted to 0.009; 1; 2; 4; and
      7 mM of Fe-EDTA. In both species there was an increase in the concentration of
      Fe, Zn, P, and Ca and a decrease in Mn, K, and Mg in the iron plaque. Both
      species accumulated more iron in roots. In the shoots, S. parviflora showed
      higher iron content, except at 7 mM. Iron altered the contents of Fe, Cu, K, and
      Mg in roots, and of Fe, Mn, Zn, N, P, K, Ca, and Mg in shoots. The two species
      tolerated high iron concentrations and accumulated high content of this element
      in both shoots and roots. The iron did not reduce their growth. Both species are
      indicated for studies aiming restoration of iron-contaminated areas.

PMID- 24132523
TI  - Using of "pseudo-second-order model" in adsorption.
AB  - A research paper's contribution exists not only in its originality and creativity
      but also in its continuity and development for research that follows. However,
      the author easily ignores it. Citation error and quotation error occurred very
      frequently in a scientific paper. Numerous researchers use secondary references
      without knowing the original idea from authors. Sulaymon et al. (Environ Sci
      Pollut Res 20:3011-3023, 2013) and Spiridon et al. (Environ Sci Pollut Res
      20:6367-6381, 2013) presented wrong pseudo-second-order models in Environmental
      Science and Pollution Research, vol. 20. This comment pointed the errors of the
      kinetic models and offered information for citing original idea of pseudo-second
      order kinetic expression. In order to stop the proliferation of the mistake, it
      is suggested to cite the original paper for the kinetic model which provided
      greater accuracy and more details about the kinetic expression. 

PMID- 24132524
TI  - Multi-biomarker responses in green mussels exposed to PFCs: effects at molecular,
      cellular, and physiological levels.
AB  - Perfluorinated chemicals (PFCs) are extremely persistent and have been found
      extensively in the environment and wildlife. Oceans are the final sink for many
      persistent organic pollutants (POPs) including PFCs. However, to date, there has
      been a lack of studies that investigated the environmental consequences of PFCs
      on marine organisms. To fill in this gap, environmental toxicity of two dominant
      PFCs, perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), was
      examined in a sentinel species, green mussel Perna viridis, using a series of
      biomarkers corresponding to different biological levels (molecular, cellular, and
      physiological). Correlations among these biomarkers were also investigated. The
      results showed that the tested compounds can induce a series adverse effect at
      different biological levels, including oxidative stress, DNA damage, membrane
      instability, suppressed filtration rate, and reduced body weight. Correlation
      analysis revealed that excess production of reactive oxygen species could be the
      major toxic pathway. An indirect mode of toxic action was also explored where
      adverse impacts could be secondary effects of PFC exposure. The joint analysis of
      biomarkers from multiple biological levels resulted in a comprehensive
      understanding of how PFC exposure can influence the health of organisms. The
      correlations of these biomarkers also provided a new perspective of the
      ecological consequences of PFCs. 

PMID- 24132525
TI  - Accumulation of eosinophils, mast cells, and basophils in the spleen and the
      coronary arteries in anaphylactic deaths: is the Kounis hypersensitivity
      associated syndrome present?

PMID- 24132527
TI  - Interaction between simultaneous contraction and relaxation in different limbs.
AB  - We investigated the interaction between relaxation and contraction for remote,
      ipsilateral muscles of the hand and foot (wrist extensor/ankle dorsiflexor).
      Subjects sat in an armchair and were able to freely move their right hand and
      foot. They performed eight tasks: (1) wrist extension from a flexed (relaxed)
      position, (2) ankle dorsiflexion from a plantarflexed (relaxed) position, (3)
      wrist relaxation from an extended position, (4) ankle relaxation from a
      moderately dorsiflexed position. The remaining tasks involved (5) simultaneous
      performance of tasks 1 and 2, (6) 3 and 4, (7) 1 and 4, and (8) 2 and 3. Subjects
      performed each task as fast as possible after hearing a start signal. They were
      instructed not to activate antagonistic muscles in the tasks involving
      relaxation. When contraction of the wrist flexor/ankle dorsiflexor was concurrent
      with relaxation of the ipsilateral limb (ankle dorsiflexor/wrist extensor), the
      reaction time of contraction as observed in electromyography (EMG) activities in
      the wrist extensor/ankle dorsiflexor became longer and the EMG activities became
      smaller. Our findings suggest that muscle relaxation in one limb interferes with
      smooth movement of muscle contraction in the ipsilateral limb.

PMID- 24132528
TI  - Bridging the gap between different measures of the reading speed deficit in
      developmental dyslexia.
AB  - The study assessed how decoding and pronunciation times contribute to total
      reading time in reading aloud and how these measures change in the presence of
      developmental dyslexia. Vocal reaction times (RTs), pronunciation times, and
      total reading times were measured while 25 children with dyslexia and 43 age
      matched typically developing readers read singly presented words and non-words
      that varied for length. Group differences were large for vocal RTs; children with
      dyslexia were increasingly slower as a function of condition difficulty (over
      additivity effect); lexicality and length influenced RTs even when over
      additivity was controlled for by z-score transformation. The group differences
      were also large for vocal total reading times, but the effect of over-additivity
      was smaller than that of vocal RTs and no selective influence of lexicality and
      length was detected. Pronunciation times showed very small individual differences
      and no over-additivity effect; children with dyslexia were more sensitive to the
      effect of lexicality and length than controls. To assess the contribution of the
      cognitive and sensory-motor compartments in determining group differences, we
      applied the difference engine model. As for RTs, the relationship between means
      and standard deviations closely supported the prediction of a general cognitive
      delay in the slow group, with no group difference in the sensory-motor
      compartment. The variance in total reading times was predicted by combining the
      model results for RTs with the linear relationship between pronunciation times
      and task difficulty. The results help clarify the internal structure of reading
      times, a measure largely used in clinical testing to assess reading rate.

PMID- 24132526
TI  - Contribution of vision to postural behaviors during continuous support-surface
      translations.
AB  - During standing balance, kinematics of postural behaviors have been previously
      observed to change across visual conditions, perturbation amplitudes, or
      perturbation frequencies. However, experimental limitations only allowed for
      independent investigation of such parameters. Here, we adapted a pseudorandom
      ternary sequence (PRTS) perturbation previously used in rotational support
      surface perturbations (Peterka in J Neurophysiol 88(3):1097-1118, 2002) to a
      translational paradigm, allowing us to concurrently examine the effects of
      vision, perturbation amplitude, and frequency on balance control. Additionally,
      the unpredictable PRTS perturbation eliminated effects of feedforward adaptations
      typical of responses to sinusoidal stimuli. The PRTS perturbation contained a
      wide spectral bandwidth (0.08-3.67 Hz) and was scaled to 4 different peak-to-peak
      amplitudes (3-24 cm). Root mean square (RMS) of hip displacement and velocity
      increased relative to RMS ankle displacement and velocity in the absence of
      vision across all subjects, especially at higher perturbation amplitudes. Gain
      and phase lag of center of mass (CoM) sway relative to the perturbation also
      increased with perturbation frequency; phase lag further increased when vision
      was absent. Together, our results suggest that visual input, perturbation
      amplitude, and perturbation frequency can concurrently and independently modulate
      postural strategies during standing balance. Moreover, each factor contributes to
      the difficulty of maintaining postural stability; increased difficulty evokes a
      greater reliance on hip motion. Finally, despite high degrees of joint angle
      variation across subjects, CoM measures were relatively similar across subjects,
      suggesting that the CoM is an important controlled variable for balance.

PMID- 24132529
TI  - Fecal transplantation therapy for Clostridium difficile-associated pouchitis.

PMID- 24132531
TI  - [Are high glucose levels a risk factor for dementia? High blood glucose levels
      increase the risk of dementia--not only in diabetes].

PMID- 24132530
TI  - Preoperative adipocytokines as a predictor of surgical infection after colorectal
      surgery: a prospective survey.
AB  - BACKGROUND: Infections are the leading cause of morbidity and mortality after
      colorectal surgery. Obesity is a well-known risk factor for wound infection, but
      it does not seem to increase the risk of other infectious complications. The aim
      of this study was to look for a relationship between the fatty tissue metabolism
      measured by adipocytokine levels and the risk of postoperative infection.
      PATIENTS AND METHODS: Preoperative plasma levels of eight adipocytokines,
      cholesterol, triglycerides, insulin and C-reactive protein (CRP) were measured in
      consecutive patients undergoing elective colorectal surgery between June 2008 and
      June 2011. Information about epidemiological and clinical characteristics was
      obtained for each patient. All infections in the 30 days following surgery were
      recorded. RESULTS: Among the 174 patients included, 49 (28 %) presented with a
      postoperative infection: 41 surgical site infections and 8 other infections.
      Preoperative leptin, insulin and CRP were significantly higher in patients with
      postoperative infection (p = 0.025, p = 0.020 and p = 0.044, respectively), but
      only leptin was predictive of infection in multivariate analysis (odds ratio (OR)
      = 1.89, 95 % confidence interval (CI) 1.18-3.03, p = 0.008). The predictive value
      of leptin was slightly lower for surgical site infection (OR = 1.65, 95 % CI 1.06
      2.55, p = 0.025). Leptin levels were independent of the other adipocytokine
      levels but not of the body mass index. CONCLUSION: Although markers of
      inflammation and insulin resistance are also related to the onset of surgical
      infection, leptin correlates more closely with the risk of infection than does
      any other factor. However, its effect could be partially mediated by the body
      mass index.

PMID- 24132532
TI  - [Uncommon solid abdominal tumor].
AB  - HISTORY AND ADMISSION FINDINGS: A 67-year-old female patient got ill during
      holidays in USA with acute abdominal pain. She was discharged after symptomatic
      treatment and presented afterwards in Germany for further clarification and
      treatment. INVESTIGATIONS, TREATMENT AND COURSE: Following abdominal sonography,
      gastroscopy and CT scan with contrast medium, a gastrointestinal stromal tumor
      (GIST) was assumed. Thereupon a tumor extirpation with cholecystectomy and liver
      resection was performed. After laparotomy a solid fibrous abdominal tumor could
      be diagnosed histologically. There was no indication for an adjuvant treatment.
      CONCLUSION: In the international literature reports about these tumors are rare.
      A complete resection is essential; there is no data for an adjuvant treatment.

PMID- 24132533
TI  - [63-year-old patient with soft tissue ulcers of both lower legs].

PMID- 24132534
TI  - [Opiate induced constipation--mechanisms, relevance and treatment].

PMID- 24132536
TI  - [Not Available].

PMID- 24132535
TI  - [Renal denervation: ready for prime time?].

PMID- 24132537
TI  - [Not Available].

PMID- 24132538
TI  - [Not Available].

PMID- 24132540
TI  - An unusual cause of acute abdomen in an adolescent with concurrent disease.

PMID- 24132541
TI  - A pilot test of a church-based intervention to promote multiple cancer-screening
      behaviors among Latinas.
AB  - We assessed the feasibility, acceptability, and initial impact of a church-based
      educational program to promote breast, cervical, and colorectal cancer screening
      among Latinas ages 18 years and over. We used a one-group pre-/post-evaluation
      within a low-income, Latino Baptist church in Boston, MA. Participants completed
      interviewer-administered assessments at baseline and at the end of the 6-month
      intervention. Under the guidance of a patient navigator (PN), women from the
      church (peer health advisors, or PHAs) were trained to deliver evidence-based
      screening interventions, including one-to-one outreach, small group education,
      client reminders, and reduction of structural barriers to screening. The PN and
      PHAs also implemented a health fair, and the pastor integrated health information
      into regular sermons. At pre-intervention, nearly half of the sample did not meet
      screening guidelines. The majority (97%, n = 35) of those who completed the post
      intervention assessment participated in intervention activities. Two thirds (67%)
      reported talking with the PN or PHAs about health issues. Participation in small
      group education sessions was highest (72%), with health fairs (61%) and goal
      setting (50%) also being popular activities. Fourteen percent also reported
      receiving help from the PN in finding a primary care provider. This study
      supports the feasibility and acceptability of churches as a setting to promote
      cancer screening among Latinas.

PMID- 24132542
TI  - Sustainability in a state comprehensive cancer control coalition: lessons
      learned.
AB  - The Alabama Comprehensive Cancer Control Coalition (ACCCC) has developed an
      integrated and coordinated approach to reducing cancer incidence, morbidity, and
      mortality, and to improving the quality of life for cancer survivors, their
      families, and their caregivers. The ACCCC is currently in a maintenance phase and
      a formal plan for sustainability of the coalition was needed to keep the members
      engaged and productive. A training session in coalition sustainability conducted
      in 2013 identified the following elements as essential to success: (1) increased
      marketing of the coalition by simplifying its mission; (2) improved networking
      including flexibility in coalition meeting location and attendance; (3) increased
      membership satisfaction through transformational leadership; (4) revision of the
      working structure of committees and improved accountability; and (5) enhancement
      of partner satisfaction with coalition activities designed to recruit and retain
      new partners. A self-administered membership satisfaction survey was given to
      assess coalition mission, meeting logistics, organization, capacity building, and
      coalition goals. Results indicated that the subcategories of communication,
      mission, and meeting logistics were rated satisfied to very satisfied on a five
      point scale. Although the ACCCC had clearly written goals, improvement could be
      made in leadership participation and new member orientation could be improved.
      Most members rated their parent organization as highly involved with the ACCCC
      and many offered suggestions on capacity building. Results of the sustainability
      training have clarified the ACCCC's plans to ensure coalition viability and
      improve strategies to inform stakeholders of the benefits of participation in the
      coalition. 

PMID- 24132543
TI  - Lay abstracts and summaries: writing advice for scientists.
AB  - Scientific journals, institutional review boards, and funding sources often
      require abstracts or research summaries written specifically for the lay public.
      Making research findings understandable to the public helps raise awareness and
      speed adoption of practices that may lead to improved health. We provide advice
      on writing lay abstracts and summaries which includes the following: (1) make
      reasonable assumptions about grade-level, vocabulary, prior experience, and
      interests of the audience; (2) practice a verbal explanation with someone from
      your audience; (3) start writing by using a simple headline followed by a brief
      and relevant synopsis in common language then expand; (4) read your draft aloud
      and revise; (5) check readability statistics and simplify as needed; and (6) have
      both lay audience and peer scientists read your summary to assure that it is
      accessible to the public while remaining true to the science. 

PMID- 24132544
TI  - The play is now reality: affective turns, narrative struggles, and theorizing
      emotion as practical experience.
AB  - Discursive approaches to subjectivity have been critiqued most recently for its
      dismissal of a living body that moves and senses. While identity as performative
      has proven invaluable to contemporary cultural theory for its dynamic
      conceptualization of power in everyday practice, the emergence of what some
      scholars have named an "affective turn" has prompted calls for configuring the
      body as more than a complex set of significations, but also a vibrant energy
      field in perpetual emergence. Centered on an enacted story created by two
      clinical therapists and two South Asian immigrant domestic violence survivors
      during a therapeutic support group session, this paper brings the affective turn
      into dialog with narrative theory. I juxtapose two different readings of this
      clinical "performance." One interpretation recognizes affect theory's value for
      highlighting sensation and the virtual in moments of transformation. Nonetheless
      I argue it overlooks a lived history. Thus, using a specifically dramatistic
      approach to narrative, the second analysis stresses the importance of personal
      experience and meaning-making in strengthening the link between affect and
      subjectivity. In doing so, the case study also argues for emotion's critical link
      to practical and moral experience. 

PMID- 24132547
TI  - Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients
      with human herpesvirus 6B-associated acute encephalopathy with biphasic seizures
      and late reduced diffusion.
AB  - Acute encephalopathy with biphasic seizures and late reduced diffusion has become
      increasingly common among various types of human herpesvirus 6B (HHV-6B)
      encephalitis at the time of primary viral infection. The aim of the present study
      is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with
      biphasic seizures and late reduced diffusion. Five cytokines and five chemokines
      were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B
      associated acute encephalopathy with biphasic seizures and late reduced diffusion
      patients and 19 control exanthem subitum (without complications) patients. Serum
      interleukin (IL)-10 (P = 0.007) and IL-8 (P = 0.025) were significantly higher in
      the patients with the disease than controls. Serum IL-1beta (P = 0.034) and
      monocyte chemoattractant protein (MCP)-1 (P = 0.002) were significantly higher in
      the controls than patients with the disease. In patients with the disease, IL-10
      (P = 0.012), regulated on activation normal T cell expressed and secreted
      (RANTES; P = 0.001), and monokine induced by interferon gamma (MIG; P = 0.001)
      were significantly higher in serum than CSF, meanwhile IL-6 (P = 0.034), IL-8 (P
      = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum.
      Additionally, serum IL-10 was significantly higher in the disease patients with
      sequelae than those without sequelae (P = 0.016). Several cytokines and
      chemokines may be associated with the pathogenesis of acute encephalopathy with
      biphasic seizures and late reduced diffusion. Moreover, the regulation of
      cytokine networks appears to be different between peripheral blood (systemic) and
      central nervous system.

PMID- 24132546
TI  - Current therapeutic strategies for childhood hepatic tumors: surgical and
      interventional treatments for hepatoblastoma.
AB  - Surgery is the mainstay of multimodal treatment for hepatoblastomas. Among the
      various staging systems used, PRETEXT is currently adopted in all major study
      groups worldwide as a common pretreatment staging system. Although variations of
      treatment strategies among study groups exist, the majority of hepatoblastoma
      cases currently undergo preoperative chemotherapy. It is therefore critical to
      determine the optimal surgical treatment during the initial courses of
      chemotherapy. Patients with PRETEXT IV tumors, multifocal tumors and tumors
      invading major vessels of the liver are candidates for liver transplantation.
      Liver transplantation requires preparation in advance, and consultation to a
      liver expertise team must take place no later than after two cycles of
      chemotherapy. The existence of pulmonary metastasis is a predictor of poor
      prognosis of the patient. Surgery for pulmonary nodules should be considered for
      those patients remaining positive after cycles of chemotherapy. A considerable
      number of patients have been reported to achieve long-term survival after
      resecting pulmonary metastasis. The existence of pulmonary metastasis at
      diagnosis is no longer a contraindication for liver transplantation, provided
      that the pulmonary nodules are eliminated by chemotherapy or by metastasectomy.
      Transcatheter arterial chemoembolization (TACE) is a useful tool for the local
      control of hepatoblastomas, although there are very few reports statistically
      supporting the significant advantage of this treatment modality. Based on
      individual cases, TACE could be beneficial in maximizing the anti-tumor effect
      with less toxic side effects. 

PMID- 24132548
TI  - Culturally Tailored Depression/Suicide Prevention in Latino Youth: Community
      Perspectives.
AB  - Latino adolescents are at elevated risk for depression and suicide compared to
      other ethnic groups. Project goals were to gain insight from community leaders
      about depression risk factors particular to Latino adolescents and generate
      innovative suggestions to improve cultural relevance of prevention interventions.
      This project utilized a CBPR approach to enhance cultural relevance,
      acceptability, and utility of the findings and subsequent program development.
      Two focus groups of youth and youth-involved Latino community leaders (n = 18)
      yielded three overarching themes crucial to a culturally tailored depression
      prevention intervention: (1) utilize a multipronged and sustainable intervention
      approach, (2) raise awareness about depression in culturally meaningful ways, and
      (3) promote Latino youth's social connection and cultural enrichment activities.
      Findings suggest that both adaptation of existing prevention programs and
      development of hybrid approaches may be necessary to reduce depression/suicide
      disparities for Latino youth. One such hybrid program informed by community
      stakeholders is described. 

PMID- 24132549
TI  - Do weather changes influence pain levels in women with fibromyalgia, and can
      psychosocial variables moderate these influences?
AB  - The aim of this study was to examine the association between fibromyalgia pain
      and weather, and to investigate whether psychosocial factors influence this
      relationship. Women with chronic widespread pain/fibromyalgia (N = 50) enrolled
      in a larger study, were recruited from a 4-week inpatient rehabilitation program
      in Norway ( 2009-2010), and reported their pain and psychological factors up to
      three times per day (morning, afternoon, evening) for 5 weeks. These ratings were
      then related to the official local weather parameters. Barometric pressure
      recorded simultaneously impacted pain significantly while temperature, relative
      humidity, and solar flux did not. No psychological variables influenced the
      weather-pain interaction. No weather parameter predicted change in the subsequent
      pain measures. The magnitude of the inverse association between pain and
      barometric pressure was very small, and none of the psychological variables
      studied influenced the association between pain and barometric pressure. All in
      all, the evidence for a strong weather-pain association in fibromyalgia seems
      limited at best.

PMID- 24132550
TI  - Potential antitumor mechanisms of phenothiazine drugs.
AB  - In this study, three kinds of phenothiazine drugs were analyzed to explore their
      potential antitumor mechanisms. First, target proteins that could interact with
      chlorpromazine, fluphenazine and trifluoperazine were predicted. Then, the target
      proteins of the three drugs were intersected. Cell signaling pathway enrichment
      and related disease enrichment were conducted for the intersected proteins to
      extract the enrichment categories associated with tumors. By regulation network
      analysis of the protein interactions, the mechanisms of action of these target
      proteins in tumor tissue were clarified, thus confirming the potential antitumor
      mechanisms of the phenothiazine drugs. The final results of cell signaling
      pathway enrichment and related disease enrichment showed that the categories with
      the highest score were all found in tumors. Target proteins belonging to the
      tumor category included signaling pathway members such as Wnt, MAPK and retinoic
      acid receptor. Moreover, another target protein, MAPK8, could indirectly act on
      target proteins CDK2, IGF1R, GSK3B, RARA, FGFR2 and MAPK10, thereby affecting
      tumor cell division and proliferation. Therefore, phenothiazine drugs may have
      potential antitumor effects, and tumor-associated target proteins play important
      roles in the process of cell signaling transduction cascades.

PMID- 24132551
TI  - Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of
      glycoconjugates of phenanthroindolizidines alkaloids.
AB  - Glycoconjugates of phenanthroindolizidine alkaloids targeting tobacco mosaic
      virus (TMV) RNA were designed, synthesized, and evaluated for their antiviral
      activity against TMV for the first time. The glycoconjugation of (S)-6-O
      desmethylantofine (2) and 14-hydroxyltylophorines (3-6) was accomplished in three
      ways (O-glycosylation manner, using carbamoyloxy as linker arm, and using 1,2,3
      triazole as linker arm) with three different sugar units (glucose, galactose, and
      mannose). The glycoconjugates showed improved water solubility and molecule
      polarity compared with phenanthroindolizidine alkaloids. The bioassay results
      showed that C6 was a suitable position for glycoconjugation and O-glycosylation
      can increase the antiviral activity of phenanthroindolizidine alkaloids
      indicating that the introduction of sugar units can improve the antiviral
      activity profile of glycoconjugates. Two O-glycosides of (S)-6-O
      desmethylantofine, (13aS)-6-O-beta-D-galactopyranosyl-2,3-dimethoxyphenanthro
      [9,10-b]-11-indolizidinone (10) and (13aS)-6-O-beta-D-mannopyranosyl-2,3
      dimethoxyphenanthro [9,10-b]-11-indolizidinone (11) displayed significant higher
      activity than commercial ningnanmycin, and thus could be considered for novel
      therapy against plant virus infection.

PMID- 24132552
TI  - The marginating-pulmonary immune compartment in mice exhibits increased NK
      cytotoxicity and unique cellular characteristics.
AB  - To test whether marginating-pulmonary (MP) leukocytes in mice have a unique
      potential to identify and destroy aberrant circulating cells, we compared MP to
      circulating leukocytes with respect to natural killer (NK) cytotoxicity,
      proinflammatory characteristics, molecular determinants of activation, and
      response to IL-12 immunostimulation. Cytotoxicity was assessed employing the YAC
      1, B16F10, and 3LL target lines. C57BL/6 mice were injected with either saline or
      murine IL-12 (0.1 or 0.5 ug/mouse), either once or three times 48-h apart. Twenty
      four hours after last injection, cardiac blood was withdrawn and MP leukocytes
      were collected by forced lung perfusion. NK cytotoxicity, cellular composition,
      and surface molecular markers were studied. MP leukocytes exhibited greater NK
      cytotoxicity than circulating leukocytes against the syngeneic B16F10 and 3LL
      tumor lines, but not against the allogeneic YAC-1 line. NKG2D and IL-12 receptor
      expression predicted NK cytotoxicity in circulating leukocytes, but not in MP
      leukocytes. IFNgamma-receptor, IL-12-receptor, CD69, CD11a, and CD11b showed
      different patterns of expression in the two leukocyte populations, suggesting pro
      inflammatory characteristics of the MP compartment. IL-12 stimulation caused
      differential effects on these markers and also elevated cytotoxicity in both
      compartments, but in different effector: target ratio-dependent patterns. MP
      leukocytes may play a critical role in eliminating aberrant circulating cells due
      to their enhanced NK cytotoxicity and given their strategic location in the lungs
      vasculature, which forces physical interactions with all circulating aberrant
      cells. MP-NK cells are unique in their cytotoxic mechanisms against syngeneic
      targets and in their activation profile and response to immunostimulatory agents.

PMID- 24132553
TI  - Patient selection for mechanical thrombectomy.
AB  - PURPOSE: To evaluate the influence of tissue parameters as assessed by multimodal
      computed tomography and procedural parameters on clinical outcome after
      mechanical thrombectomy. METHODS: A total of 301 consecutive patients with acute
      onset ischemic stroke were included in this study. Of these, 65 had
      thromboembolic occlusions of the carotid T or middle cerebral artery (MCA) and
      underwent mechanical thrombectomy. Tissue parameters were given by unenhanced CT
      and perfusion CT (PCT) parameter maps of total hypoperfused tissue, infarct core,
      and tissue at risk. Procedural parameters comprised time from symptom onset (SO)
      to PCT, from SO to the first angiographic series, and from SO to vessel
      recanalization (occlusion time). In a subset of 22 fully recanalized occlusions,
      infarcted tissue and "tissue at risk" as defined by PCT were coregistered to
      final infarcts on follow-up imaging. RESULTS: Thrombolysis in cerebral infarction
      score (TICI) 2b/3 recanalization was achieved in 58/65 patients (89%). Only the
      infarct core size (p = 0.007) and the ratio of the infarct core relative to the
      tissue at risk (p = 0.001) yielded significant differences regarding the clinical
      outcome. Small infarct cores and low ratios of core size relative to the tissue
      at risk were correlated with a favorable outcome after mechanical thrombectomy.
      In the PCT coregistration subset, the congruency between predicted infarct cores
      and final infarcts was 68%, and between tissue at risk and final infarcts 7%,
      respectively. CONCLUSIONS: The size of the infarct core and the ratio relative to
      the tissue at risk are more relevant parameters for clinical outcome after
      mechanical thrombectomy than time related factors.

PMID- 24132555
TI  - Copy number variation of Chikungunya ECSA virus with disease symptoms among
      Indian patients.
AB  - After a gap of three decades, from 2005 onwards, a series of Chikungunya virus
      (CHIKV) outbreaks occurred worldwide. This study was performed to detect CHIKV
      infection, its genotype among symptomatic Eastern Indian patients and to analyze
      any association between the presence of CHIKV genome in patient body with
      appearance of disease symptoms (n = 199). Plasma-extracted viral RNA was reverse
      transcribed to cDNA and PCR-amplified followed by agarose gel electrophoresis.
      Viral load among CHIKV-positive patients was determined by real time RT-PCR.
      CHIKV-IgM in sera was detected by ELISA. Sequencing and phylogenetic analysis of
      plasma-extracted PCR products was done. CHIKV genome and IgM were detected among
      65.3% (n = 130) and 41.2% (n = 82) patients respectively. Joint swelling was
      significantly associated with CHIKV infection (P-value: 0.0003). CHIKV PCR
      positive patients were grouped in two categories: Group-I: viral load <10(4) 
      copies/ml and Group-II: viral load >=10(4)  copies/ml. Higher number of acute
      stage patients clustered in Group-II. Fever and joint swelling were significantly
      more prevalent among Group-II patients, whereas rash and diarrhoea among Group-I
      patients (P-value <0.05). Patient-isolated CHIKV sequences clustered with CHIKV
      ECSA genotypes in the phylogenetic tree, with two types of CHIKV strains found to
      circulate among them-as indicated by their different nucleotide sequences. This
      is the first study detecting the presence of CHIKV ECSA genotype among Eastern
      Indian patients. Fever and joint swelling might have appeared first followed by
      rash, diarrhea during disease progression-as indicated by CHIK viral load in
      patients. Thus, viral load can be used as unique diagnostic and prognostic marker
      of Chikungunya disease pathogenesis.

PMID- 24132554
TI  - A comparison of CT/CT angiography and MRI/MR angiography for imaging of
      vertebrobasilar dolichoectasia.
AB  - PURPOSE: Vertebrobasilar dolichoectasia (VBD) is a rare dilatative arteriopathy
      predominantly affecting the basilar artery (BA) and vertebral arteries. Until
      today, the value of computed tomography (CT)/CT angiography (CTA) compared with
      magnetic resonance imaging (MRI)/time-of-flight MR angiography (TOF-MRA) has not
      been studied systematically. METHODS: We (1) compare CTA and TOF-MRA according to
      the established criteria (diameter at the mid-pons level, height, and lateral
      position), (2) explore the value of further CTA- and TOF-MRA-derived measures
      (maximum transverse diameter and length), as well as (3) explore the value of
      further non-contrast-enhanced MRI sequences such as T1, fluid-attenuated
      inversion recovery, and T2* for a detailed characterization of VBD in a series of
      18 patients. RESULTS: Comparison of CTA and TOF-MRA revealed very good
      consistency of the measured diameter (Pearson's r = 0.994, p = 0.01) and the
      noted height of the BA (Kendall's tau = 1.0, p = 0.001). The same held true for
      the maximum transverse diameter (Pearson's r = 0.988, p = 0.01) and length of the
      BA (Pearson's r = 0.986, p = 0.01). In contrast to this, there was a lower
      agreement concerning the lateral position (Kendall's tau = 0.866, p = 0.01). In
      comparison with the diameter at the mid-pons level, the maximum transverse
      diameter was significantly larger (p = 0.002). Luminal thrombus was detected
      equally well by CTA and TOF-MRA. CT was useful to detect small circumscribed
      calcifications, whereas MRI was advantageous to demonstrate perifocal brainstem
      edema. CONCLUSIONS: We could demonstrate a substantial comparability of CT/CTA
      and MRI/TOF-MRA in the diagnosis of VBD. The maximum transverse diameter and
      length may be useful when an endovascular treatment is considered. Taking into
      account the different informative value of both techniques, it may be worth to
      perform both imaging procedures.

PMID- 24132556
TI  - Left ventricular noncompaction cardiomyopathy: updated review.
AB  - The first case of noncompaction was described in 1932 after an autopsy performed
      on a newborn infant with aortic atresia/coronary-ventricular fistula. Isolated
      noncompaction cardiomyopathy was first described in 1984. A review on
      selected/relevant medical literature was conducted using Pubmed from 1984 to 2013
      and the pathogenesis, clinical features, and management are discussed. Left
      ventricular noncompaction (LVNC) is a relatively rare congenital condition that
      results from arrest of the normal compaction process of the myocardium during
      fetal development. LVNC shows variability in its genetic pattern,
      pathophysiologic findings, and clinical presentations. The genetic heterogeneity,
      phenotypical overlap, and variety in clinical presentation raised the suspicion
      that LVNC might just be a morphological variant of other cardiomyopathies, but
      the American Heart Association classifies LVNC as a primary genetic
      cardiomyopathy. The familiar type is common and follows a X-linked, autosomal
      dominant, or mitochondrial-inheritance pattern (in children). LVNC can occur in
      isolation or coexist with other cardiac and/or systemic anomalies. The clinical
      presentations are variable ranging from asymptomatic patients to patients who
      develop ventricular arrhythmias, thromboembolism, heart failure, and sudden
      cardiac death. Increased awareness over the last 25 years and improvements in
      technology have increased the identification of this illness and improved the
      clinical outcome and prognosis. LVNC is commonly diagnosed by echocardiography.
      Other useful diagnostic techniques for LVNC include cardiac magnetic resonance
      imaging, computerized tomography, and left ventriculography. Management is
      symptom based and patients with symptoms have a poorer prognosis. LVNC is a
      genetically heterogeneous disorder which can be associated with other anomalies.
      Making the correct diagnosis is important because of the possible associations
      and the need for long-term management and screening of living relatives. 

PMID- 24132557
TI  - ST-segment elevation induced by coronary artery spasm during tilt-table test.

PMID- 24132558
TI  - Dabigatran and rivaroxaban prescription for atrial fibrillation in Catalonia,
      Spain: the need to manage the introduction of new drugs.

PMID- 24132559
TI  - Demodex folliculitis mimicking acute graft-vs-host disease.
AB  - IMPORTANCE: Acute graft-vs-host disease (GVHD) typically requires high-dose
      systemic steroids as first-line treatment. Like drug eruptions, viral exanthema,
      and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker
      of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex
      folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients
      who have undergone a stem cell transplant with eruptions on the head and neck.
      OBSERVATIONS: A 46-year-old white woman with a history of Fms-like tyrosine
      kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day
      history of a nonpruritic eruption on her face and neck 28 days after undergoing a
      double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings
      from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent
      to follicular units along with an abundance of Demodex mites noted within the
      hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was
      given, and the eruption cleared within 24 hours. CONCLUSIONS AND RELEVANCE: To
      our knowledge, this is only the fifth reported case of Demodex folliculitis
      following HSCT, but the first ever reported to be successfully treated with oral
      ivermectin. Demodex folliculitis should be added to the differential diagnosis of
      skin eruptions that arise after HSCT.

PMID- 24132560
TI  - Sampling for landscape elements--a case study from Lower Saxony, Germany.
AB  - The estimation of coverage, i.e., the proportion of the total area in a study
      region covered by a given target class, is essential to many aspects of
      environmental monitoring. We analyze and compare the efficiency of different
      sample-based approaches for the estimation of coverage of different land cover
      classes from aerial imagery in a case study in Lower Saxony, Germany on the basis
      of the estimated standard errors. A complete delineation of vegetation classes in
      n = 279 aerial photo plots of 400 * 400 m thrown onto the study region of 1,117.7
      km(2) in accordance with a systematic grid is compared to different
      configurations of line intercept sampling and clusters of points. The observation
      designs under study are characterized by different complexity and total size of
      the observation units and therefore also to the efforts related to yield a single
      observation. Especially for those classes that cover a relatively large
      proportion of the sampling frame, our results show that difference in performance
      between the different designs are negligible. A cluster of four transects of 200
      m each allows estimating the area of land cover classes with high coverage with
      nearly similar precision as a complete mapping of fixed area plots of 16 ha each.
      Clusters of points show unexpected high precision for the estimated coverage of
      land cover classes with relatively high coverage. 

PMID- 24132561
TI  - Clinical impact of albuminuria and glomerular filtration rate on renal and
      cardiovascular events, and all-cause mortality in Japanese patients with type 2
      diabetes.
AB  - BACKGROUND: The number of patients suffering from diabetic nephropathy resulting
      in end-stage kidney disease is increasing worldwide. In clinical settings, there
      are limited data regarding the impact of the urinary albumin-to-creatinine ratio
      (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and
      cardiovascular outcomes and all-cause mortality. METHODS: We performed a
      historical cohort study of 4328 Japanese participants with type 2 diabetes from
      10 centers. Risks for renal events (requirement for dialysis or transplantation,
      or half reduction in eGFR), cardiovascular events (cardiovascular death, nonfatal
      myocardial infarction, or nonfatal stroke), and all-cause mortality were assessed
      according to UACR and eGFR levels. RESULTS: During follow-up (median 7.0 years,
      interquartile range 3.0-8.0 years), 419 renal events, 605 cardiovascular events
      and 236 deaths occurred. The UACR levels increased the risk and the adjusted
      hazard ratios for these three events. In addition to the effects of UACR levels,
      eGFR stages significantly increased the adjusted hazard ratios for renal events
      and all-cause mortality, especially in patients with macroalbuminuria. Diabetic
      nephropathy score, based on the prognostic factors, well predicted incidence
      rates per 1000 patient/year for each event. CONCLUSIONS: Increased UACR levels
      were closely related to the increase in risks for renal, cardiovascular events
      and all-cause mortality in Japanese patients with type 2 diabetes, whereas the
      association between high levels of UACR and reduced eGFR was a strong predictor
      for renal events.

PMID- 24132562
TI  - Abnormal lipoprotein metabolism in diabetic nephropathy.
AB  - It is well known that patients with diabetes have a high incidence of
      cardiovascular disease (CVD), and the incidence of CVD becomes substantially
      elevated with development of diabetic nephropathy. The mechanisms for
      dyslipidemia in diabetic nephropathy are multifactorial and complex. Long-term
      hyperglycemia causes generalized vascular endothelial damage, which reduces
      functional lipoprotein lipase, leading to increased triglyceride (TG) levels and
      decreased high-density lipoprotein cholesterol (HDL-C). In overt-diabetic
      nephropathy, hypoproteinemia markedly increases low-density lipoprotein
      cholesterol (LDL-C), and renal failure specifically increases remnant
      lipoproteins and decreases HDL-C and LDL-C. Overt diabetic nephropathy exhibits
      remarkable postprandial hypertriglyceridemia with hyper-apolipoprotein (apo) B48,
      a marker of chylomicron and its remnants. Apo CIII is a key inhibitor of
      lipolysis and particle uptake of TG-rich lipoproteins, which is specifically
      increased in advanced chronic kidney disease, irrespective of the presence of
      diabetes. LDL size becomes smaller with advanced stages of diabetic nephropathy,
      whereas LDL size is not reduced in hemodialysis patients (HD). HD patients have
      marked lower levels of HDL3-C than controls. HD patients also have substantially
      low apo AI and high serum amyloid A (SAA) levels, suggesting the replacement of
      apo AI by SAA is stimulated in HDL particles. 

PMID- 24132563
TI  - Prognostication in neurocritical care: just crystal ball gazing?

PMID- 24132564
TI  - Glibenclamide in cerebral ischemia and stroke.
AB  - The sulfonylurea receptor 1 (Sur1)-transient receptor potential 4 (Trpm4) channel
      is an important molecular element in focal cerebral ischemia. The channel is
      upregulated in all cells of the neurovascular unit following ischemia, and is
      linked to microvascular dysfunction that manifests as edema formation and
      secondary hemorrhage, which cause brain swelling. Activation of the channel is a
      major molecular mechanism of cytotoxic edema and "accidental necrotic cell
      death." Blockade of Sur1 using glibenclamide has been studied in different types
      of rat models of stroke: (i) in conventional non-lethal models (thromboembolic, 1
      2 h temporary, or permanent middle cerebral artery occlusion), glibenclamide
      reduces brain swelling and infarct volume and improves neurological function;
      (ii) in lethal models of malignant cerebral edema, glibenclamide reduces edema,
      brain swelling, and mortality; (iii) in models with rtPA, glibenclamide reduces
      swelling, hemorrhagic transformation, and death. Retrospective studies of
      diabetic patients who present with stroke have shown that those whose diabetes is
      managed with a sulfonylurea drug and who are maintained on the sulfonylurea drug
      during hospitalization for stroke have better outcomes at discharge and are less
      likely to suffer hemorrhagic transformation. Here, we provide a comprehensive
      review of the basic science, preclinical experiments, and retrospective clinical
      studies on glibenclamide in focal cerebral ischemia and stroke. We also compare
      the preclinical work in stroke models to the updated recommendations of the
      Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here
      provide a strong foundation for a translational research program to study
      glibenclamide in patients with ischemic stroke.

PMID- 24132565
TI  - Self-fulfilling prophecies through withdrawal of care: do they exist in traumatic
      brain injury, too?
AB  - OBJECTIVE: We examined factors associated with withdrawal of care (WOC) in
      moderate-severe traumatic brain injury (msTBI) patients, and how WOC may affect
      short-term mortality and receipt of neurosurgery. Variability in msTBI-related
      outcome prognostication by clinicians from different specialties was also
      assessed. METHODS: Rates of WOC, factors associated with WOC, and the relation
      between WOC and in-hospital case-fatality rate (CFR) and neurosurgery were
      determined in 232 prospectively enrolled msTBI patients in the ongoing OPTIMISM
      Study at a level-1 trauma center. In a concomitant web-based survey with clinical
      vignettes, outcome prognostication comfort, treatment aggressiveness, and WOC
      recommendations were examined among 106 respondents from neurology, neurocritical
      care, neurosurgery, trauma and anesthesia/critical care. RESULTS: The average age
      of the study sample was 53 years, with a median Glasgow Coma Scale of 6. The in
      hospital CFR was 36 and 68 % of patients had WOC. Factors independently
      associated with WOC were advanced age, pupillary reactivity, lower intensive care
      unit-length-of-stay, pre- and in-hospital cardiac arrest, herniation,
      intracranial pressure crisis, and pre-existing endocrine disease. Inclusion of
      WOC in our multivariable regression model predicting in-hospital CFRs negated all
      other variables. Survey results suggested that in younger patients, some
      clinicians prognosticated overly pessimistically based upon data available at the
      time of presentation. CONCLUSION: In our msTBI cohort, WOC was the most important
      predictor of in-hospital mortality. We identified several important independent
      predictors of WOC. Large within-center variability in msTBI outcome
      prognostication with varying levels of possible clinical nihilism exists, which
      may form the basis of self-fulfilling prophecies.

PMID- 24132566
TI  - Validation of clinical prediction scores in patients with primary intracerebral
      hemorrhage.
AB  - BACKGROUND: Initial reports of the FUNC score suggest that it may accurately
      identify those patients suffering from intracerebral hemorrhage (ICH) with an
      ultra low chance of functional neurologic recovery. This study's aim is to
      validate the FUNC score and determine if it accurately identifies the cohort of
      patients with an ultra low chance of survival with good neurologic recovery.
      METHODS: Retrospective review of 501 consecutive primary ICH patients admitted
      from the Emergency Department to a large healthcare system. Performance of the
      FUNC, ICH-GS, and oICH scores was determined by calculating areas under the
      receiver-operator-characteristic curves. Patients with a predicted 100 % chance
      of poor neurologic outcome (PNO) (FUNC <4 and ICH-GS >10) scores were evaluated
      to determine if DNR impacted 90 day survival or rate of survival with a Glasgow
      Outcome Score of <3. RESULTS: In 366 cases of primary ICH who presented during
      the study period, 222(61 %) survived to discharge. Both the FUNC (AUC: 0.873) and
      ICH-GS (AUC: 0.888) outperformed the oICH (AUC: 0.743) in predicting 90-day
      mortality (p = <0.001). Of 68 patients with a FUNC score <4, 67 (98.5 %) had PNO
      at discharge. The presence of DNR was not associated with a significant
      difference in the rate of PNO at discharge (40/40 = 100 % vs. 27/28 = 96.4 % p =
      0.42) or 90-day mortality (40/40 = 100 % vs. 21/28 = 75 %, p = 0.06). CONCLUSION:
      The FUNC and ICH-GS appear superior to the oICH in predicting outcome in patients
      with primary ICH. In addition, the FUNC score appears to accurately identify
      patients with low chance of functional neurologic recovery at discharge.

PMID- 24132567
TI  - Therapeutic hypothermia reduces middle cerebral artery flow velocity in patients
      with severe aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Transcranial Doppler (TCD) is widely used to detect and follow up
      cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia
      might influence blood flow velocities assessed by TCD. The aim of the study was
      to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH.
      METHODS: In 20 patients treated with hypothermia (33 degrees ) due to refractory
      intracranial hypertension or delayed cerebral ischemia (DCI), mean flow velocity
      of the middle cerebral artery (MFV(MCA)) was assessed by TCD. Thirteen patients
      were treated with combined hypothermia and barbiturate coma and seven with
      hypothermia alone. MFV(MCA) was obtained within 24 h before and after induction
      of hypothermia as well as before and after rewarming. RESULTS: Hypothermia was
      induced on average 5 days after SAH (range 1-12) and maintained for 144 h (range
      29-270). After hypothermia induction, MFV(MCA) decreased from 113.7 +/- 49.0 to
      93.8 +/- 44.7 cm/s (p = 0.001). The decrease was independent of SAH-related
      complications and barbiturate coma. MFV(MCA) further decreased by 28.2 cm/s
      between early and late hypothermia (p < 0.001). This second decrease was observed
      in patients with DCI (p < 0.001), but not in patients with intracranial
      hypertension (p = 0.715). Compared to late hypothermia, MFV(MCA) remained
      unchanged after rewarming (65.6 +/- 32.1 vs 70.3 +/- 36.8 cm/s; p = 0.219).
      However, patients treated with hypothermia alone showed an increase in MFV(MCA)
      after rewarming (p = 0.016). CONCLUSION: Therapeutic hypothermia after SAH
      decreases Doppler blood flow velocity in both intracranial hypertension and DCI
      cases. The results can be the effect of hypothermia-related mechanisms or
      resolving cerebral vasospasm during prolonged hypothermia.

PMID- 24132568
TI  - DELIGHT (delay of impaired glucose tolerance by a healthy lifestyle trial) - a
      feasibility study on implementing a program of sustainable diabetes prevention in
      German companies.
AB  - BACKGROUND: Ca. 50% of Germans develop prediabetes in their lifetime. Though
      diabetes type 2 has been proven preventable, no screening for prediabetes has
      been implemented. DELIGHT was designed to assess if screening for individuals at
      risk and long-standing diabetes prevention is feasible in the setting of
      companies within the scope of the German legal health system. MATERIALS AND
      METHODS: In 5 companies employees with a waist circumference of >= 94 (men) and
      >= 80 cm (women) were offered a check-up. Those with fasting plasma glucose >=
      100 mg/dl (IFG) or >= 140 mg/dl 2 h after oral glucose load (IGT) were followed
      for 3 years with an optional moderate lifestyle program during the first year and
      quarterly assistance for another 2 years. RESULTS: In 241 of 300 participants the
      self-measured waist circumference was confirmed as elevated. 3% had type 2
      diabetes, while 37% had IFG (isolated in 96%) or IGT, of whom 91.4% (men) and
      76.1% (women) had a metabolic syndrome. Within 3 years in those who had lost >= 1
      kg, weight was reduced by 3.9 kg, risk factors were improved, and no case of
      diabetes had developed, while among those with weight loss of < 1 kg or weight
      gain, 10% of men and 5% of women had developed diabetes type 2. Screening for
      prediabetes did not increase the number or costs of drug prescriptions.
      CONCLUSIONS: Companies provide a suitable setting for screening for prediabetes.
      Long-term diabetes prevention is successfully feasible within the narrow
      financial frame of a legal insurance system without rise of costs.

PMID- 24132569
TI  - A novel peroxinectin involved in antiviral and antibacterial immunity of mud
      crab, Scylla paramamosain.
AB  - Peroxinectin (PX) with cell adhesion and peroxidase activities is important in
      invertebrate immune responses. We identified a novel PX homolog from Scylla
      paramamosain (designated as Sp-PX) through transcriptome sequencing. The full
      length of cDNA sequence was 3,165 bp. And there was a peroxidase domain in the
      deduced protein sequence. A cell-adhesive sequence (KGD motif) was also found in
      the N-terminus. The predicted molecular mass of the mature protein is 83.9 kDa,
      with an estimated pI of 6.21. At the amino acid level, Sp-PX shared much higher
      similarities with other crustaceans PX proteins. And Sp-PX also exhibited some
      similarities with other peroxidase family members. According to real-time
      polymerase chain reaction, Sp-PX was mainly distributed in the hemocytes. The
      gene expression levels in the hemocytes of the normal and white spot syndrome
      virus (WSSV)-challenged crabs were compared via high-throughput RNA sequencing
      technology, and the results showed that Sp-PX was upregulated at 48 h post-WSSV
      challenge. Subsequently, how Sp-PX responds to WSSV stimulus was explored through
      time-course experiments. The Sp-PX transcripts dramatically increased and reached
      the highest level at 12 h post-injection, whereas Sp-PX transcripts were
      recovered at 96 h post-challenge. Meanwhile, it was found that the WSSV copies
      proliferated significantly after a period of latent viral infection for 48 h. In
      addition,Sp-PX transcripts were also upregulated after Vibrio harveyi or
      Staphylococcus aureus challenge. Overall, Sp-PX not only participates in
      antibacterial immunity but also plays a crucial role in the antiviral immune
      responses of mud crab at the early stage of WSSV infection. 

PMID- 24132570
TI  - Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are
      translated into aggregating dipeptide repeat proteins.
AB  - Massive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the
      most common known cause of familial frontotemporal lobar degeneration (FTLD) and
      amyotrophic lateral sclerosis (ALS). Despite its intronic localization and lack
      of an ATG start codon, the repeat region is translated in all three reading
      frames into aggregating dipeptide-repeat (DPR) proteins, poly-(Gly-Ala), poly
      (Gly-Pro) and poly-(Gly-Arg). We took an antibody-based approach to further
      validate the translation of DPR proteins. To test whether the antisense repeat
      RNA transcript is also translated, we raised antibodies against the predicted
      products, poly-(Ala-Pro) and poly-(Pro-Arg). Both antibodies stained p62-positive
      neuronal cytoplasmic inclusions throughout the cerebellum and hippocampus
      indicating that not only sense but also antisense strand repeats are translated
      into DPR proteins in the absence of ATG start codons. Protein products of both
      strands co-aggregate suggesting concurrent translation of both strands. Moreover,
      an antibody targeting the putative carboxyl terminus of DPR proteins can detect
      inclusion pathology in C9orf72 repeat expansion carriers suggesting that the non
      ATG translation continues through the entire repeat and beyond. A highly
      sensitive monoclonal antibody against poly-(Gly-Arg), visualized abundant
      inclusion pathology in all cortical regions and some inclusions also in
      motoneurons. Together, our data show that the GGGGCC repeat is bidirectionally
      translated into five distinct DPR proteins that co-aggregate in the
      characteristic p62-positive TDP-43 negative inclusions found in FTLD/ALS cases
      with C9orf72 repeat expansion. Novel monoclonal antibodies against poly-(Gly-Arg)
      will facilitate pathological diagnosis of C9orf72 FTLD/ALS.

PMID- 24132571
TI  - Revising the daily values may affect food fortification and in turn nutrient
      intake adequacy.
AB  - The Nutrition Facts panel on food labels in the United States currently displays
      Daily Values (DVs) that are based on outdated RDAs. The FDA has indicated that it
      plans to update the DVs based on the newer Dietary Reference Intakes (DRIs), but
      there is controversy regarding the best method for calculating new DVs from the
      DRIs. To better understand the implications of DV revisions, assuming that
      manufacturers choose to maintain current label claims for micronutrients from
      voluntarily fortified foods, we modeled intake of 8 micronutrients using NHANES
      2007-2008 data and 2 potential methods for calculating DVs: the population
      weighted Estimated Average Requirement (EAR) and the population-coverage RDA. In
      each scenario, levels of fortified nutrients were adjusted to maintain the
      current %DV. Usual nutrient intakes and percentages with usual intakes less than
      the EAR were estimated for the U.S. population and subpopulations aged >= 4 y (n
      = 7976). For most nutrients, estimates of the percentage of the U.S. population
      with intakes below the EAR were similar regardless of whether the DV corresponded
      to the population-weighted EAR or the population-coverage RDA. Potential
      decreases were observed in adequacy of nutrients of concern for women of
      childbearing age, namely iron and folate (up to 9% and 3%, respectively),
      adequacy of calcium among children (up to 6%), and adequacy of vitamin A intakes
      in the total population (5%) assuming use of the population-weighted EAR compared
      with the population-coverage RDA for setting the DV. Results of this modeling
      exercise will help to inform decisions in revising the DVs.

PMID- 24132572
TI  - Supplementation with fish oil as a source of n-3 fatty acids does not
      downregulate mammary lipogenesis in lactating mice.
AB  - The very long chain n-3 (omega-3) polyunsaturated fatty acids (VLCn3PUFAs) are
      potent regulators of hepatic lipid synthesis, but their effect on lipid synthesis
      in the lactating mammary gland is less well investigated. The objective of the
      present study was to examine effects of fish oil (FO) supplementation on mammary
      lipogenesis and the expression of lipogenic genes in mammary and hepatic tissues
      of lactating mice. Beginning on day 6 of lactation and continuing for 7 d, female
      C57BL/6J mice (n = 8/diet) were fed 1 of 3 dietary treatments: a 5%-fat diet
      containing mainly saturated fatty acids (FAs) (low-fat control) or 2 10%-fat
      diets, 1 enriched with FO as a source of VLCn3PUFAs and the other enriched with a
      safflower/palm oil mixture (high-fat control) as a source of oleic acid. Mammary
      lipogenic capacity, measured by (14)C-glucose incorporation into FAs by mammary
      explants, was similar among treatments, and there were no treatment effects on
      the proportion of de novo synthesized FAs in milk fat or on litter weight gain, a
      proxy for milk energy secretion. Also, there were no treatment effects on mammary
      mRNA abundance for key lipogenic enzymes and proteins involved in the regulation
      of milk lipid synthesis. In contrast, there was a treatment effect on hepatic
      lipogenesis, with FO resulting in a decrease of ~50% in hepatic lipid content and
      a similar downregulation of lipogenic gene expression compared with the 2 control
      diets. Overall, there were tissue-specific differences in dietary VLCn3PUFA
      effects on lipid synthesis with no observed effects for mammary lipogenic
      variables but marked reductions occurring in hepatic lipogenesis.

PMID- 24132573
TI  - Short-chain fatty acids activate AMP-activated protein kinase and ameliorate
      ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers.
AB  - Short-chain fatty acids (SCFAs) have been shown to promote intestinal barrier
      function, but their protective effects against ethanol-induced intestinal injury
      and underlying mechanisms remain essentially unknown. The aim of the study was to
      analyze the influence of SCFAs on ethanol-induced barrier dysfunction and to
      examine the role of AMP-activated protein kinase (AMPK) as a possible mechanism
      using Caco-2 monolayers. The monolayers were treated apically with butyrate (2,
      10, or 20 mmol/L), propionate (4, 20, or 40 mmol/L), or acetate (8, 40, or 80
      mmol/L) for 1 h before ethanol (40 mmol/L) for 3 h. Barrier function was analyzed
      by measurement of transepithelial resistance and permeation of fluorescein
      isothiocyanate-labeled dextran. Distribution of the tight junction (TJ) proteins
      zona occludens-1, occludin, and filamentous-actin (F-actin) was examined by
      immunofluorescence. Metabolic stress was determined by measuring oxidative
      stress, mitochondrial function, and ATP using dichlorofluorescein diacetate,
      dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, and bioluminescence assay,
      respectively. AMPK was knocked down by small interfering RNA (siRNA), and its
      activity was assessed by a cell-based ELISA. Exposure to ethanol significantly
      impaired barrier function compared with controls (P < 0.0001), disrupted TJ and F
      actin cytoskeleton integrity, and induced metabolic stress. However, pretreatment
      with 2 mmol/L butyrate, 4 mmol/L propionate, and 8 mmol/L acetate significantly
      alleviated the ethanol-induced barrier dysfunction, TJ and F-actin disruption,
      and metabolic stress compared with ethanol-exposed monolayers (P < 0.0001). The
      promoting effects on barrier function were abolished by inhibiting AMPK using
      either compound C or siRNA. These observations indicate that SCFAs exhibit
      protective effects against ethanol-induced barrier disruption via AMPK
      activation, suggesting a potential for SCFAs as prophylactic and/or therapeutic
      factors against ethanol-induced gut leakiness. 

PMID- 24132574
TI  - Colonic hydrogen generated from fructan diffuses into the abdominal cavity and
      reduces adipose mRNA abundance of cytokines in rats.
AB  - Hydrogen (H2) protects against inflammation-induced oxidative stress.
      Nondigestible saccharides (NDSs) enhance colonic H2 production. We examined
      whether colonic H2 transfers to tissues in the abdominal cavity and whether it
      affects expression of proinflammatory cytokines. In Expts. 1 and 2, rats were fed
      diets containing fructooligosaccharides [FOSs; 25 (Expt. 1) and 50 g/kg (Expts. 1
      and 2)] for 7 and 14 d, respectively. The no-FOS diet was used as the control
      diet. At the end of the experiment, H2 excretion and the portal H2 concentration
      were significantly greater in the FOS group than in the control group. In the FOS
      group, the arterial H2 concentration was no more than 1.5% of the portal H2
      concentration (P = 0.03). The H2 concentration in abdominal cavity tissues,
      especially adipose tissue, in the FOS group was 5.6- to 43-fold of that in the
      control group (P < 0.05). The H2 content in the abdominal cavity in the FOS group
      was 11-fold of that in the control group (P < 0.05). In Expt. 3, rats were fed a
      high-fat diet containing FOS and inulin (50 g/kg) for 28 d. The area under the
      curve for H2 excretion between 0 and 28 d and portal and adipose H2
      concentrations were significantly higher in the FOS and inulin groups than in the
      high-fat control group. Adipose mRNA abundance of nuclear factor kappa-light
      chain-enhancer of activated B cells 1 was lower in the FOS group than in the
      control group (P = 0.02) and those of interleukin-6 and chemokine (C-C motif)
      ligand 2 tended to be lower (P < 0.11). Colonic H2 generated from NDS diffuses to
      the abdominal cavity before transferring to abdominal tissues. Reduced cytokine
      expression by FOS feeding might be dependent on increased colonic H2. Colonic H2
      may have important implications in the suppressive effect on metabolic syndrome
      via oxidative stress. 

PMID- 24132575
TI  - The challenge of meeting nutrient needs of infants and young children during the
      period of complementary feeding: an evolutionary perspective.
AB  - Breast-fed infants and young children need complementary foods with a very high
      nutrient density (particularly for iron and zinc), especially at ages 6-12 mo.
      However, in low-income countries, their diet is usually dominated by cereal-based
      porridges with low nutrient density and poor mineral bioavailability.
      Complementary feeding diets typically fall short in iron and zinc and sometimes
      in other nutrients. These gaps in nutritional adequacy of infant diets have
      likely been a characteristic of human diets since the agricultural revolution
      ~10,000 y ago. Estimates of nutrient intakes before then, based on hypothetical
      diets of preagricultural humans, suggest that infants had much higher intakes of
      key nutrients than is true today and would have been able to meet their nutrient
      needs from the combination of breast milk and premasticated foods provided by
      their mothers. Strategies for achieving adequate nutrition for infants and young
      children in modern times must address the challenge of meeting nutrient needs
      from largely cereal-based diets.

PMID- 24132576
TI  - Intakes of dietary folate and other B vitamins are associated with risks of
      esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.
AB  - Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and
      methylation. Efficient folate metabolism requires other B vitamins and is
      adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may
      develop through a process involving inflammation [reflux esophagitis (RE)]
      leading to metaplasia [Barrett's esophagus (BE)] and carcinoma. Within a
      population-based, case-control study, we investigated associations between
      dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases
      had histologically confirmed disease; RE cases had endoscopically visible
      inflammation. Controls, age-sex frequency matched to EAC cases, were selected
      through population and general practice registers. Participants underwent
      structured interviews and completed food-frequency questionnaires. Multivariate
      ORs and 95% CIs were computed using logistic regression. A total of 256 controls
      and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with
      increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P
      trend < 0.01). Similar trends were found for BE (P-trend < 0.01) and RE (P-trend
      = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3
      lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake
      was positively associated with EAC. For EAC, there was a borderline significant
      interaction between folate intake and smoking (P-interaction = 0.053); compared
      with nonsmokers with high (>= median) folate intake, current smokers with low
      intakes (<median) had an 8-fold increased risk (OR: 8.15; 95% CI: 3.61, 18.40).
      The same group had increased BE risk (OR: 2.93; 95% CI: 1.24, 6.92; P-interaction
      = 0.12). Folate and other dietary methyl-group factors are implicated in the
      etiology of EAC and its precursors.

PMID- 24132577
TI  - Resistant starch induces catabolic but suppresses immune and cell division
      pathways and changes the microbiome in the proximal colon of male pigs.
AB  - Consumption of resistant starch (RS) has been associated with various intestinal
      health benefits, but knowledge of its effects on global gene expression in the
      colon is limited. The main objective of the current study was to identify genes
      affected by RS in the proximal colon to infer which biologic pathways were
      modulated. Ten 17-wk-old male pigs, fitted with a cannula in the proximal colon
      for repeated collection of tissue biopsy samples and luminal content, were fed a
      digestible starch (DS) diet or a diet high in RS (34%) for 2 consecutive periods
      of 14 d in a crossover design. Analysis of the colonic transcriptome profiles
      revealed that, upon RS feeding, oxidative metabolic pathways, such as the
      tricarboxylic acid cycle and beta-oxidation, were induced, whereas many immune
      response pathways, including adaptive and innate immune system, as well as cell
      division were suppressed. The nuclear receptor peroxisome proliferator-activated
      receptor gamma was identified as a potential key upstream regulator. RS
      significantly (P < 0.05) increased the relative abundance of several butyrate
      producing microbial groups, including the butyrate producers Faecalibacterium
      prausnitzii and Megasphaera elsdenii, and reduced the abundance of potentially
      pathogenic members of the genus Leptospira and the phylum Proteobacteria.
      Concentrations in carotid plasma of the 3 main short-chain fatty acids acetate,
      propionate, and butyrate were significantly higher with RS consumption compared
      with DS consumption. Overall, this study provides novel insights on effects of RS
      in proximal colon and contributes to our understanding of a healthy diet. 

PMID- 24132578
TI  - Increased adiponectin associated with poor survival in hepatocellular carcinoma.
AB  - BACKGROUND: Alterations of adiponectin (APN), one of the adipokines, have been
      associated with human cancers. However, the clinical significance and impacts of
      APN on hepatocellular carcinoma (HCC) remain undetermined. METHODS: Using
      immunohistochemistry, expression patterns of APN were semiquantitatively scored
      and further statistically correlated with clinicopathological characteristics and
      patient survival. Furthermore, the bioeffects and underlying mechanisms of
      ectopic APN overexpression were determined in Hep3B and HepG2 cells by XTT,
      immunoblotting, flowcytometry, and invasion assays with or without chemical
      inhibitors and neutralization antibody. RESULTS: We found that cytoplasmic APN
      staining in 85 cancerous lesions was increased and associated with a poor
      survival rate (P = 0.007), even when using the Cox regression model (OR = 3.590;
      95 % CI = 1.240-10.394; P = 0.018). Ectopic overexpression of APN in Hep3B and
      HepG2 cells increased proliferation and invasion as well as the levels of p-AKT
      (Ser473), p-STAT3 (Tyr705), and those downstream, i.e., cyclin D1 and beta
      catenin. Similar results were also demonstrated in a stable APN-overexpressing
      clone, HepG2#136. APN neutralization antibody and LY294002 blocked the APN
      mediated effects via inhibition of activated AKT. CONCLUSIONS: Our results
      suggest that increased APN may contribute to HCC at least in part through its
      activation of AKT signalling and may serve as a prognostic factor in HCC.

PMID- 24132579
TI  - Control and modulation of fluid flow in the rat kidney.
AB  - We have developed a mathematical model of the rat's renal hemodynamics in the
      nephron level, and used that model to study flow control and signal transduction
      in the rat kidney. The model represents an afferent arteriole, glomerular
      filtration, and a segment of a short-loop nephron. The model afferent arteriole
      is myogenically active and represents smooth muscle membrane potential and
      electrical coupling. The myogenic mechanism is based on the assumption that the
      activity of nonselective cation channels is shifted by changes in transmural
      pressure, such that elevation in pressure induces vasoconstriction, which
      increases resistance to blood flow. From the afferent arteriole's fluid delivery
      output, glomerular filtration rate is computed, based on conservation of plasma
      and plasma protein. Chloride concentration is then computed along the renal
      tubule based on solute conservation that represents water reabsorption along the
      proximal tubule and the water-permeable segment of the descending limb, and
      chloride fluxes driven by passive diffusion and active transport. The model's
      autoregulatory response is predicted to maintain stable renal blood flow within a
      physiologic range of blood pressure values. Power spectra associated with time
      series predicted by the model reveal a prominent fundamental peak at ~165 mHz
      arising from the afferent arteriole's spontaneous vasomotion. Periodic external
      forcings interact with vasomotion to introduce heterodynes into the power
      spectra, significantly increasing their complexity. 

PMID- 24132580
TI  - Establishing diagnostic criteria for occult hepatitis B virus infections in
      community based populations.
AB  - Present diagnostic criteria for occult hepatitis B virus (HBV) infection requires
      blood or liver samples to test positive for at least two HBV DNA targets in
      hepatitis B surface antigen (HBsAg) negative individuals. These criteria were
      derived from studies involving referred or selected patient populations. The
      objective of the present study was to determine whether the present definition of
      occult HBV infection also applies within a nonselected community based
      population. HBV DNA testing was performed in 1,007 HBsAg negative sera by real
      time PCR with primer sets targeting the Enhancer I (ENHI), precore/core and
      surface/polymerase (S) genomic regions. Real time PCR positive cases were
      analyzed further by nested PCR. The results were then correlated with serologic
      findings among HBV DNA negative and occult positive individuals. Fifty-five sera
      (5.5%) were positive for at least one of the three genomic regions. Positive
      results with at least two primer/probe sets (thereby satisfying present
      diagnostic criteria for occult HBV infection) were identified in 8 (0.8%) samples
      (3 ENHI plus S, 2 ENHI plus precore/core and 3 having positive results with all
      three primer/probe sets). The prevalence of HBV serologic markers in samples that
      tested positive for only one primer set were similar to those of HBV DNA negative
      matched controls, thereby arguing against their representing occult infection.
      The results of this study suggest that the present diagnostic criteria for occult
      HBV infection are also appropriate for population based studies. However, further
      studies are required to confirm that impression.

PMID- 24132581
TI  - Hospital length of stay and readmission: an early investigation.
AB  - This article is an investigation into the relationship between length of stay and
      readmission within 30 days of discharge from an acute care hospitalization. We
      estimated probability models for heart attack and for heart failure patients
      using generalized estimating techniques applied to hospital administrative data
      from California for calendar year 2008. The key independent variable was length
      of stay in the initial hospitalization. We found negative associations between
      length of stay and readmission probability, particularly in the case of heart
      attack. Simulated values of predicted readmissions based on a 1-day increase in
      length of stay yielded estimated reductions in readmission rates in the 7% to 18%
      range for heart attack patients and the 1% to 8% range for heart failure
      patients. Increasing length of stay for some patients may be a means of improving
      quality of care by reducing readmission during the 30-day postdischarge period. 

PMID- 24132582
TI  - Improving hospital efficiency: a process model of organizational change
      commitments.
AB  - Improving hospital efficiency is a critical goal for managers and policy makers.
      We draw on participant observation of the perioperative coaching program in seven
      Ontario hospitals to develop knowledge of the process by which the content of
      change initiatives to increase hospital efficiency is defined. The coaching
      program was a change initiative involving the use of external facilitators with
      the goal of increasing perioperative efficiency. Focusing on the role of
      subjective understandings in shaping initiatives to improve efficiency, we show
      that physicians, nurses, administrators, and external facilitators all have
      differing frames of the problems that limit efficiency, and propose different
      changes that could enhance efficiency. Dynamics of strategic and contested
      framing ultimately shaped hospital change commitments. We build on work
      identifying factors that enhance the success of change efforts to improve
      hospital efficiency, highlighting the importance of subjective understandings and
      the politics of meaning-making in defining what hospitals change. 

PMID- 24132583
TI  - Structure and formation mechanism of calcium phosphate concretions formed in
      simulated body fluid.
AB  - Synthetic calcium phosphate (CaP) concretions in the form of hemispheres formed
      under carefully controlled conditions (pH 7.4, 37  degrees C, no evaporation)
      from stagnant simulated body fluid on anionic polymeric substrate (laminin) were
      observed by scanning and transmission electron microscopy and atomic force
      microscopy. The hemispheres with diameter between approximately 50 and 200 MUm
      were composed of closely connected round spherical and elliptical objects of
      diameter varying from 70 to 120 nm with surface layer composed of tightly packed
      spherical objects of diameter 25-30 nm. The phase composition of concretions
      consisting of amorphous material was uniform. The concretions were formed by
      aggregation of CaP clusters (Posner's clusters Ca9(PO4)3 or [Ca3(PO4)2] n )
      generated in the solution by perikinetic coagulation, their settling onto a
      substrate and subsequent accumulation through surface migration (surface
      nucleation) followed by accretion of nanoparticles arriving from surrounding
      solution. The similarity of ultrafine structures of these synthetic CaP
      concretions and the compact phosphatic phase appearing in some phosphate calculi
      indicates that analogous mechanisms could be active at the formation of the
      latter in the kidneys.

PMID- 24132584
TI  - Depth dose comparison of measured and calculated dose for the Eclipse virtual
      carbon couch top models with air gap variation.
AB  - This study assessed the accuracy of EclipseTM (Varian Medical Systems, Palo Alto,
      CA, USA) treatment planning system (TPS) dose calculations when using virtual
      couch top models to account for couch presence in patient treatments. The Flat
      panel and Unipanel couch tops for the Varian Exact Couch were used in this study.
      Assigned Hounsfield unit (HU) for the virtual couch tops were varied and TPS
      calculated dose was compared to measured data to determine an optimal assigned
      HU. Air gaps of up to 10 cm were introduced between couch and phantom to assess
      the ability of the models to replicate dose in this situation, commonly seen
      clinically. Dose was measured at a range of depths, for each air gap thickness,
      in order to assess the model both near surface and at various depths beyond the
      dose maximum. Optimal HU was taken to be that which had the best agreement
      between measured and calculated dose over the range of gaps and depths tested.
      For the Flat panel couch top this was found to be -500 HU and for the Unipanel
      couch top, -200 HU. Default HU parameters originally set in the models was found
      to be not optimal for the whole range of depths studied. With optimal HU
      parameters set, there was good agreement between calculated and measured dose for
      depths greater than 0.5 cm, but discrepancies were still observed near surface.
      When implementing virtual couch top models, users could improve dose calculation
      accuracy by determining the optimal HU from comparisons over several clinical
      depths rather than a single depth. 

PMID- 24132585
TI  - Diffuse eruption of necrotic papules and nodules.

PMID- 24132586
TI  - [Concept of reconstructive body shaping in obesity. Evidence-based therapy
      algorithm].
AB  - Interdisciplinary obesity centers are medically required for the successful
      treatment of obese patients. Due to the dramatic increase in the number of obese
      patients needing treatment, it is important to develop interdisciplinary therapy
      approaches based on clinically and scientifically based knowledge with high
      levels of evidence. The recent S3 guideline "Surgery of the obese" represents
      such an evidence-based interdisciplinary approach. In this concept, postbariatric
      plastic surgery has also been integrated. This article presents an evidence-based
      therapy algorithm that was developed. 

PMID- 24132587
TI  - Contamination of therapeutic human immunoglobulin preparations with
      apolipoprotein H (beta2-glycoprotein I).
AB  - Polyclonal immunoglobulin (Ig) concentrates are important biological medicinal
      products and the assurance of their quality and safety is crucial. In our present
      approach we used proteomic methods to check the purity of commercial Ig products
      of different origin. The experimental setup included nonreducing 2DE or DIGE
      combined with MALDI-TOF and the thrombin generation assay, a routine safety test
      for pharmaceutical Ig preparations, and was complemented by a specific
      immunoassay. 2DE patterns displayed contaminations with trace amounts of human
      apolipoprotein H (Apo-H), transferrin, albumin, and its fragments. In contrast to
      the latter, Apo-H is a protein that is active in the coagulation cascade, and
      thus a potential involvement in thromboembolic events in vivo cannot be excluded.
      It was found by 2DE and MALDI-TOF to be a contaminant of several Ig preparations.
      Spiking experiments of Ig preparations with pure Apo-H demonstrated an Apo-H
      concentration dependent increase in thrombin generation assay values. Traces of
      Apo-H are possibly also contributing to unwanted side effects, as already known
      for factor XIa. The significance of Apo-H contaminations for these side effects
      might be verified by detailed analyses of pharmacovigilance data. 

PMID- 24132588
TI  - Selected physicochemical properties of AH Plus, EndoREZ and RealSeal SE root
      canal sealers.
AB  - The aim of this laboratory study was to assess selected physicochemical
      properties of three root canal sealers. The solubility, setting time and
      radiopacity of AH Plus, EndoREZ and RealSeal SE were evaluated. The solubility
      was determined by weight loss of specimens in water over a period of 28 days.
      Setting time and radiopacity were assessed according to ANSI/ADA and ISO
      specifications using an aluminum step wedge calibrated in millimeters and the
      intendention test using a Gilmore needle. Data were analyzed using ANOVA and the
      Student-Newman-Keuls test for pairwise comparisons. AH Plus was significantly
      less soluble, showed the significantly highest radiopacity and displayed the
      significantly longest setting time of all sealers (P < 0.01). At all exposure
      times, EndoREZ was significantly more soluble than the other sealers (P < 0.01)
      and displayed the significantly lowest values regarding radiopacity (P < 0.01).
      Analysis showed that setting time and radiopacity for all sealers met the
      ANSI/ADA and ISO standards. Solubility of AH Plus and RealSeal confirmed the
      ANSI/ADA and ISO specification, while EndoREZ clearly exceeded the proposed
      solubility value. Out of all sealers tested, AH Plus obtained the best values for
      all properties. 

PMID- 24132589
TI  - Significant association between MTHFR C677T polymorphism and hepatocellular
      carcinoma risk: a meta-analysis.
AB  - Previous studies investigated the association between methylenetetrahydrofolate
      reductase (MTHFR) C677T polymorphism and hepatocellular carcinoma risk, but the
      impact of MTHFR C677T polymorphism on hepatocellular carcinoma was still unclear,
      owing to the obvious inconsistence from those studies. This study aimed to
      quantify the strength of the association between MTHFR C677T polymorphism and
      hepatocellular carcinoma risk by performing a meta-analysis. We searched the
      PubMed and Wanfang databases for studies on the association between MTHFR C677T
      polymorphism and hepatocellular carcinoma risk. We estimated the pooled odds
      ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the
      association. Fifteen studies with 8,625 participants were finally included into
      the meta-analysis. Meta-analyses of total 15 studies suggested that MTHFR C677T
      polymorphism was significantly associated with an increased risk of
      hepatocellular carcinoma under two main genetic models (for TT versus CC, OR =
      1.19, 95% CI 1.03-1.37, P = 0.016; for TT versus CT/CC, OR = 1.14, 95% CI 1.01
      1.28, P = 0.032). Subgroup meta-analyses suggested that MTHFR C677T polymorphism
      was associated with an increased risk of hepatocellular carcinoma in Asians, but
      not in Caucasians. Thus, individuals with homozygote genotype TT of MTHFR C677T
      have obviously increased risk of hepatocellular carcinoma.

PMID- 24132590
TI  - Aberrant Beclin 1 expression is closely linked to carcinogenesis,
      differentiation, progression, and prognosis of ovarian epithelial carcinoma.
AB  - Beclin 1, an important autophagy-related protein in human cells, is involved in
      autophagy, differentiation, anti-apoptosis, and cancer suppression, which is
      increased during periods of cell stress and extinguished during cell cycle. Human
      ovarian tumors display allelic loss of Beclin 1 with high frequency. To clarify
      Beclin 1's role in ovarian carcinogenesis and subsequent progression, its
      expression was examined by immunostaining on tissue microarrays containing
      ovarian normal tissue, benign and borderline tumors, and carcinomas. Beclin 1
      mRNA and protein expression was examined in ovarian normal tissue, benign and
      borderline tumors, carcinoma tissue, and cell lines by reverse transcription
      polymerase chain reaction or Western blot, respectively. The results demonstrated
      that the higher Beclin 1 mRNA was observed in ovarian benign tumor than normal
      ovary and ovarian carcinoma (P < 0.05) and negatively correlated with the
      differentiation of ovarian carcinoma (P < 0.05). Beclin 1 protein expression was
      stronger in ovarian carcinoma than that in normal ovary and inversely related to
      the differentiation of ovarian carcinoma (P < 0.05) by Western blot.
      Immunohistochemically, Beclin 1 expression was statistically higher in ovarian
      borderline tumor and carcinoma than normal ovary and benign tumor (P < 0.05) and
      inversely linked to differentiation, lower ki-67 expression, and higher
      cumulative or relapse-free survival rate of ovarian carcinoma (P < 0.05). Cox
      proportional hazard model indicated that age and International Federation of
      Gynecology and Obstetrics staging (P < 0.05), but not pathological classification
      differentiation degree or Beclin 1 expression, were independent prognostic
      factors for overall and relapse-free ovarian carcinomas (P > 0.05). It was
      suggested that the aberrant Beclin 1 expression is closely linked to
      tumorigenesis and differentiation of ovarian carcinoma. Beclin 1 expression might
      be employed to indicate the worse prognosis of ovarian carcinomas, albeit not an
      independent factor. 

PMID- 24132591
TI  - MicroRNA-128 promotes proliferation in osteosarcoma cells by downregulating PTEN.
AB  - MicroRNAs are a class of small noncoding RNAs that function as critical gene
      regulators through targeting mRNAs for translational repression or degradation.
      Several studies have indicated that abnormal expression of miRNAs occurs
      frequently in human osteosarcoma. In the present study, we found that miR-128
      expression was significantly increased in osteosarcoma tissues compared to
      adjacent normal tissues. Ectopic overexpression of miR-128 significantly promoted
      while suppression of miR-128 by its antisense inhibited the proliferation of MG63
      and U2OS cells. At the molecular level, our results demonstrated that miR-128
      overexpression could repress expression of PTEN by directly targeting PTEN 3'
      untranslated region. Consistently, downstream AKT signaling was altered by miR
      128 overexpression or knockdown. Therefore, our results suggest that miR-128
      plays an important role in the proliferation of human osteosarcoma cells by
      directly regulation of PTEN/AKT signaling. 

PMID- 24132592
TI  - Support by trained mentor mothers for abused women: a promising intervention in
      primary care.
AB  - BACKGROUND: Intimate partner violence (IPV) against women is a major health
      problem and negatively affects the victim's mental and physical health. Evidence
      based interventions in family practice are scarce. OBJECTIVE: We aimed to
      evaluate a low threshold home-visiting intervention for abused women provided by
      trained mentor mothers in family practice. The aim was to reduce exposure to IPV,
      symptoms of depression as well as to improve social support, participation in
      society and acceptance of mental health care. METHODS: A pre-post study of a 16
      week mentoring intervention with identified abused women with children was
      conducted. After referral by a family doctor, a mentor mother visited the abused
      woman weekly. Primary outcomes are IPV assessed with the Composite Abuse Scale
      (CAS), depressive symptoms using the Symptom Checklist (SCL 90) and social
      support by the Utrecht Coping List. Secondary outcomes are analysed
      qualitatively: participation in society defined as employment and education and
      the acceptance of mental health care. RESULTS: At baseline, 63 out of 66 abused
      women were referred to mentor support. Forty-three participants completed the
      intervention programme. IPV decreased from CASt otal 46.7 (SD 24.7) to 9.0 (SD
      9.1) (P <= 0.001) after the mentor mother support programme. Symptoms of
      depression decreased from 53.3 (SD 13.7) to 34.8 (SD 11.5) (P <= 0.001) and
      social support increased from 13.2 (SD 4.0) to 15.2 (SD 3.5) (P <= 0.001).
      Participation in society and the acceptance of mental health for mother and child
      improved. CONCLUSIONS: Sixteen weekly visits by trained mentor mothers are a
      promising intervention to decrease exposure to IPV and symptoms of depression, as
      well as to improve social support, participation in society and the acceptance of
      professional help for abused women and their children.

PMID- 24132593
TI  - Impact of body mass index on prevalence of multimorbidity in primary care: cohort
      study.
AB  - BACKGROUND: Multimorbidity is the co-occurrence of long-term conditions. Obesity
      is associated with an increased risk of long-term conditions including type 2
      diabetes and depression. OBJECTIVE: To quantify the association between body mass
      index (BMI) category and multimorbidity in a large cohort registered in primary
      care. METHODS: The sample comprised primary care electronic health records of
      adults aged >=30 years, sampled from the Clinical Practice Research Datalink
      between 2005 and 2011. Multimorbidity was defined as the co-occurrence of >=2 of
      11 conditions affecting seven organ systems. Age- and sex-standardized prevalence
      of multimorbidity was estimated by BMI category. Adjusted odds ratios associating
      BMI with additional morbidity were estimated adjusting for socioeconomic
      deprivation and smoking. RESULTS: The sample comprised 300 006 adults. After
      excluding participants with BMI never recorded, data were analysed for 223 089
      (74%) contributing 1 374 109 person-years. In normal weight men, the standardized
      prevalence of multimorbidity was 23%, rising to 27% in overweight, 33% in
      category I obesity, 38% in category II and 44% in category III obesity. In women,
      the corresponding values were 28%, 34%, 41%, 45% and 51%. In category III
      obesity, the adjusted odds, relative to normal BMI, were 2.24 (2.13-2.36) for a
      first condition; 2.63 (2.51-2.76) for a second condition and 3.09 (2.92-3.28) for
      three or more conditions. In a cross-sectional analysis, 32% of multimorbidity
      was attributable to overweight and obesity. CONCLUSIONS: Multiple morbidity is
      highly associated with increasing BMI category and obesity, highlighting the
      potential for targeted primary and secondary prevention interventions in primary
      care.

PMID- 24132595
TI  - Pachyonychia congenita in pediatric patients: natural history, features, and
      impact.
AB  - IMPORTANCE Nail dystrophy in early childhood often suggests a diagnosis of
      pachyonychia congenita (PC). No previous investigation has focused on the early
      signs of PC and the natural course of the disease. OBJECTIVES To determine the
      course of pediatric PC, correlate the disease course with the clinical appearance
      and specific gene mutations, and assess the effect of pediatric PC on quality of
      life. DESIGN, SETTING, AND PARTICIPANTS One hundred one patients or families with
      genetically confirmed PC from the International Pachyonychia Congenita Research
      Registry who completed a survey on the general clinical features of PC and an
      auxiliary questionnaire on the clinical presentation and quality-of-life issues
      related to pediatric PC. EXPOSURE Individuals with pachyonychia congenita. MAIN
      OUTCOMES AND MEASURES Completion of both surveys. RESULTS At birth, toenail
      changes were present in 47.5% of patients; fingernail changes in 40.6%; and
      plantar keratoderma in 6.9%. By 5 years of age, these 3 key manifestations were
      found in 81.2%, 74.2%, and 75.3%, respectively, of individuals with genotype
      confirmed PC. The correct diagnosis was made during the first year of life in
      26.7% of patients despite the presence of toenail dystrophy in more than 65.3%.
      Clinical differences that distinguished PC subtypes included (1) later onset and
      less frequent occurrence of nail dystrophy and keratoderma in PC-K6b, PC-K6c, and
      PC-K16; (2) concurrent fingernail and toenail thickening in PC-K6a and PC-K17;
      (3) more palmar keratoderma in PC-K16; (4) cysts primarily in PC-K17 and
      follicular hyperkeratoses primarily in PC-K6a; (5) hoarseness and/or oral
      leukokeratoses in the first year of life most often in PC-K6a; and (6) natal
      teeth exclusively in PC-K17. Among pediatric patients, PC affected the social
      interactions and function of adolescents most profoundly. CONCLUSIONS AND
      RELEVANCE Among patients with a detectable mutation, PC manifests with nail
      thickening and plantar keratoderma before school age in more than three-quarters
      of affected children, allowing early diagnosis. The highly visible nail changes
      and painful plantar thickening exert a psychosocial effect on most affected
      adolescents. Phenotype-genotype correlations in children with PC validate the new
      classification based on the affected gene. 

PMID- 24132594
TI  - Utility of the Aintree Intubation Catheter in fiberoptic tracheal intubation
      through the three types of intubating supraglottic airways: a manikin simulation
      study.
AB  - PURPOSE: The purpose of this study was to examine the utility of the Aintree
      Intubation Catheter (AIC) with three types of supraglottic airway devices for
      tracheal intubation (ISGAs) using a manikin. METHODS: Participants were 21
      anesthesiologists with more than 2 years of experience in clinical anesthesia.
      Three types of ISGAs were passed through the glottis: Fastrack-Single Use (FSU;
      size 4), air-Q (size 3.5), and i-gel (size 4). Participants attempted fiberoptic
      tracheal intubation with the ISGAs in random order. Success rate of tracheal
      intubation, intubation time, and collision with the glottis were recorded.
      Participants also evaluated the subjective difficulty of the entire intubation
      process and passing the tracheal tube through the glottis using a Visual Analogue
      Scale. RESULTS: The FSU required a significantly longer time for intubation
      compared with the other two ISGAs (p < 0.05). AIC use did not significantly
      improve the success rate of intubation or shorten intubation times for any of the
      ISGAs. However, there were significantly more collisions with the glottis without
      AIC use for the FSU and air-Q compared to when they were used with the AIC (FSU,
      p = 0.015; air-Q, p = 0.025). CONCLUSION: Among the ISGAs tested, intubation took
      longer with the FSU, and the FSU had a higher failure rate than the other ISGAs.
      AIC significantly decreased the number of collisions with the FSU and air-Q.
      These findings suggest that the AIC is effective in reducing collisions with the
      tracheal tube and thus will reduce the risk of mechanical injury to the airway.

PMID- 24132596
TI  - [Direct costs of diabetes mellitus in Germany: first estimation of the
      differences related to educational level].
AB  - OBJECTIVE: There are many studies on health inequalities, but these are rarely
      combined with cost-of-illness analyses. If the cost-of-illness were to be
      calculated for the individual status groups, it would be possible to assess the
      economic potential of preventive measures aimed specifically at people from low
      status groups. The objective of this article is to demonstrate for the first time
      the preventive potential by taking the example of diabetes mellitus (DM) from an
      economic perspective. METHODS: Based on a systematic literature review, the
      average direct costs per patient with DM were assessed. Then, the prevalence of
      DM among adults with different educational levels was estimated based on the
      nationwide survey 'German Health Update' (GEDA), conducted by the Robert Koch
      Institute in Germany in 2009. Finally, the cost and prevalence data were used to
      calculate the direct costs for each educational level. RESULTS: The direct costs
      of DM amount to about 13.1 billion ? per year; about 35% of these costs can be
      attributed to patients with a low educational level. Thus, their share of the
      total costs is about 67% higher than their share of the total population. If the
      prevalence in the group with 'low educational level' (14.8%) could be reduced to
      the prevalence in the group with 'middle educational level' (7.9%), this would
      save about 2.2 billion (about 16.5%) ? of direct costs. DISCUSSION: The analysis
      provides a first estimate of the potential savings from an effective status
      specific prevention programme. However, the direct costs per patient used were
      only an average for all people with DM, as a breakdown by educational level was
      not available. Since education can also affect health behaviour and compliance,
      which are also determinants of cost, the analyses presented here are probably
      conservative.

PMID- 24132597
TI  - Comparison of microfabricated hexagonal and lamellar post arrays for DNA
      electrophoresis.
AB  - We used Brownian dynamics simulations to compare DNA separations in
      microfabricated post arrays containing either hexagonal or lamellar lattices.
      Contrary to intuition, dense hexagonal arrays with frequent DNA post collisions
      do not yield the optimal separation. Rather, hexagonal arrays with pore sizes
      commensurate with the radius of gyration of the DNA lead to increased separation
      resolution due to a molecular weight dependent collision probability that
      increases with molecular weight. However, when the hexagonal array is too sparse,
      this advantage is lost due to the low number of collisions. Lamellar lattices,
      such as the DNA nanofence, appear to be superior to a hexagonal array at the same
      post density, since the lamellar lattice combines regions for DNA relaxation with
      locally dense post regions for collisions. The relative advantages of different
      post arrays designs are explained in terms of the statistics for the number of
      collisions and the holdup time, providing guidelines for designing post arrays
      for separating long DNA. 

PMID- 24132598
TI  - Polychlorinated biphenyls, polybrominated diphenyl ethers, and phthalates in
      roach from the Seine River basin (France): impact of densely urbanized areas.
AB  - Endocrine disruptors (EDs) from three chemical classes-polychlorinated biphenyls
      (PCBs), polybrominated diphenyl ethers (PBDEs), and phthalates-were investigated
      in the Seine River and one tributary, the Orge River, upstream and downstream of
      urban areas. The impact of urban areas was characterized by a concentration
      increase of all compounds in the Seine River and for phthalates and PBDEs in the
      Orge River. In the Seine River, from upstream (Marnay) to downstream (Triel) of
      urban areas, water concentration increases were greater for diethylhexyl
      phthalate (DEHP) (6 times, p < 0.05) and ?tri-hexa BDE (5 times [p < 0.05]) than
      for ?7PCBi (2.6 times). Simultaneously, sediments displayed a strong accumulation
      of contaminants downstream and compared with upstream values, their
      concentrations increased greatly: 202-fold for DEHP, 69-fold for BDE209, 25-fold
      for ?tri-hexa-BDE, and 11-fold for ?7PCBi. Variations of fish ED concentrations
      gave an indication of their habitat contamination increase observed downstream of
      densely urbanized areas of the Seine River, especially for PBDEs (?tri-hexa-PBDEs
      = 14-fold increase <=15.7 +/- 6.9 ng g(-1) dry weight [dw; p < 0.001]) and for
      PCBs (?7PCBi eightfold increase <=211 +/- 55 ng g(-1) dw [p < 0.01]). PCA results
      highlighted relationships between the different ED classes. A correlation (p <
      0.05) was observed between PCB and PBDE fish concentrations, suggesting common
      sources and similar absorption mechanisms. For PCBs, which were poorly
      biodegraded, the bioaccumulation factor was strongly correlated (p < 0.001) to
      molecular hydrophobicity, whereas for PBDEs a negative correlation (p < 0.05) was
      observed related active debromination processes. This multichemical study
      investigates for the first time the occurrence of a wide range of EDs in roach,
      which was chosen as a sentinel species for this survey of surface water
      contamination. 

PMID- 24132600
TI  - Welfare based primate rehabilitation as a potential conservation strategy: does
      it measure up?
AB  - Many primate species are threatened with extinction and are the focus of
      extensive conservation efforts including re-introduction, captive breeding and
      habitat conservation. Welfare-based rehabilitation (hereafter also
      'rehabilitation') is a management strategy commonly used for primates,
      particularly those species targeted by the pet and bush meat trades.
      Rehabilitation of rescued primates typically has the dual motivation of welfare
      and conservation, but has not been assessed as a conservation strategy. As the
      species involved in rehabilitation are often endangered (e.g. chimpanzees,
      gorillas, orang-utans), it is important for rehabilitation projects to follow a
      'best practice' model in order to increase positive outcomes. In this study, we
      compared the approaches of 28 welfare-based primate rehabilitation projects to
      the 'IUCN guidelines for nonhuman primate re-introductions', in addition to
      components of the 'Best practice guidelines for the re-introduction of great
      apes' in order to assess where additional work might be needed for released
      animals to contribute to conservation outcomes. Few projects examined complied
      with the guidelines for re-introduction, failing to incorporate important factors
      such as quarantine, long term post-release monitoring and training for predator
      awareness. Further development of species-specific rehabilitation guidelines may
      improve the outcomes of future rehabilitation projects. To support this, we
      recommend that detailed methods and results be published for all rehabilitation
      efforts, regardless of the outcome. 

PMID- 24132599
TI  - Detecting hepatocellular carcinoma in gadoxetic-acid-enhanced hepatobiliary-phase
      MR imaging at 3T: comparing high and low flip angle.
AB  - PURPOSE: We evaluated the diagnostic performance of fat-suppressed 3D T1-weighted
      gradient-echo magnetic resonance imaging (MRI) sequences for the hepatobiliary
      phase of gadoxetic-acid-enhanced liver MRI between low and high flip angle (FA)
      at 3T. MATERIALS AND METHODS: Forty-six patients with 62 HCCs were enrolled in
      this retrospective study from among 267 consecutive patients who underwent 3T MRI
      with low and high FA (10 degrees  and 25 degrees ) sequences at the hepatobiliary
      phase. A radiologist measured signal intensities and standard deviations (SD) of
      lesion, liver, and spleen and calculated signal-to-noise ratio, liver-spleen
      contrast, and liver-lesion contrast. Two reviewers assessed both image sequences
      using a five-point rating scale focusing on detecting hypointense lesions.
      RESULTS: The high FA sequence showed significantly higher liver-spleen and liver
      lesion contrast compared with those of low FA (p < 0.05, p < 0.05, respectively).
      Per-lesion sensitivities of high FA were higher than those of low FA (p < 0.05, p
      < 0.05, respectively), and per-person sensitivities were elevated on high FA (p <
      0.05 in a reviewer). There were statistically significant differences for
      detecting HCCs larger than 1 cm (p < 0.05, p < 0.05, respectively). CONCLUSION:
      Increasing FA in T1-weighted hepatobiliary-phase liver MRI may help in detecting
      HCC at 3T.

PMID- 24132601
TI  - Strategic alliance, a way forward for violence against women: a case for the
      Special Cells, India.
AB  - This article attempts to describe the experiences of violated women and the
      struggles of social workers to contest violence against women in the Indian
      context. It begins with a brief account of an "indigenous model": the
      establishment of a service for violated women in India within the police force-
      the Special Cell on Violence Against Women. The article traces the strategic
      location, vision, growth, present position, expansion, and replication of the
      Special Cell in India, and discusses the necessity of working simultaneously with
      violated women, formal systems, and social structures; its contribution to the
      campaign for a Domestic Violence Act; and the resultant outcomes. The arduous
      nature of the work required for violated women and the women's own assessment of
      the Special Cells were accessed through a rigorous evaluation study, which is
      presented in the article, providing an answer and affirmation to the question:
      Why work with the Establishment--the State.

PMID- 24132602
TI  - Clinical and diagnostic developments of a gamma interferon release assay for use
      in bovine tuberculosis control programs.
AB  - Currently, the Bovigam assay is used as an official supplemental test within
      bovine tuberculosis control programs. The objectives of the present study were to
      evaluate two Mycobacterium bovis-specific peptide cocktails and purified protein
      derivatives (PPDs) from two sources, liquid and lyophilized antigen preparations.
      PPDs and peptide cocktails were also used for comparison of a second-generation
      gamma interferon (IFN-gamma) release assay kit with the currently licensed first
      generation kit (Bovigam; Prionics AG). Three strains of M. bovis were used for
      experimental challenge: M. bovis 95-1315, M. bovis Ravenel, and M. bovis 10-7428.
      Additionally, samples from a tuberculosis-affected herd (i.e., naturally
      infected) were evaluated. Robust responses to both peptide cocktails, HP (PC-HP)
      and ESAT-6/CFP10 (PC-EC), and the PPDs were elicited as early as 3 weeks after
      challenge. Only minor differences in responses to Commonwealth Serum Laboratories
      (CSL) and Lelystad PPDs were detected with samples from experimentally infected
      animals. For instance, responses to Lelystad M. avium-derived PPD (PPDa) exceeded
      the respective responses to the CSL PPDa in M. bovis Ravenel-infected and control
      animals. However, a 1:4 dilution of stimulated plasma demonstrated greater
      separation of PPDb from PPDa responses (i.e., PPDb minus PPDa) with the use of
      Lelystad PPDs, suggesting that Lelystad PPDs provide greater diagnostic
      sensitivity than CSL PPDs. The responses to lyophilized and liquid antigen
      preparations did not differ. Responses detected with first- and second-generation
      IFN-gamma release assay kits (Bovigam) did not differ throughout the study. In
      conclusion, antigens may be stored in a lyophilized state without loss in
      potency, PC-HP and PC-EC are dependable biomarkers for aiding in the detection of
      bovine tuberculosis, and second-generation Bovigam kits are comparable to
      currently used kits.

PMID- 24132603
TI  - Vectored expression of the broadly neutralizing antibody FI6 in mouse airway
      provides partial protection against a new avian influenza A virus, H7N9.

PMID- 24132604
TI  - Antigenicity of recombinant maltose binding protein-Mycobacterium avium subsp.
      paratuberculosis fusion proteins with and without factor Xa cleaving.
AB  - Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in
      ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis
      expresses certain proteins when exposed to in vitro physiological stress
      conditions similar to the conditions experienced within a host during natural
      infection. Such proteins are hypothesized to be expressed in vivo, are recognized
      by the host immune system, and may be of potential use in the diagnosis of JD. In
      this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp.
      paratuberculosis fusion proteins were evaluated using serum samples from sheep
      infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be
      antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor
      Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in
      either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and
      removal of the MBP tag was marginally enhanced.

PMID- 24132605
TI  - Evaluation of a commercial enzyme-linked immunosorbent assay for the diagnosis of
      bovine tuberculosis from milk samples from dairy cows.
AB  - Milk samples from dairy cows provide a ready source of material for measuring
      antibody responses to Mycobacterium bovis antigens. In this study, we evaluated
      the IDEXX enzyme-linked immunosorbent assay (ELISA) for the measurement of
      antibody responses to M. bovis antigens MPB70 and MPB83 in milk samples from New
      Zealand cattle. Test sensitivities for individual milk and serum samples were
      assessed in samples collected from 44 M. bovis-infected cows, and test
      specificities were assessed in milk samples collected from 356 cows from
      tuberculosis (TB)-free herds. Milk vat samples were collected from 505 herds from
      regions with relatively high or low prevalences of infection. The ELISA had a
      sensitivity of 50% and a specificity of 97.5% for milk samples, and the test
      sensitivities for milk and serum samples were the same. Dilution of the positive
      test milk samples in milk from noninfected cows at 1/10, 1/20, and 1/50 dilutions
      reduced the proportions of positive responses to 13/21, 9/21, and 4/21,
      respectively. Small differences were observed in the ELISA responses of milk
      samples from individual TB-free cows collected at different times during
      lactation. No significant differences were detected in the ELISA responses of
      milk vat samples collected from infected and noninfected herds. This study shows
      that milk samples can be substituted for serum samples for screening individual
      cows for M. bovis infection, and pooling of milk samples from 10 to 20 animals
      can result in a reduction in the sensitivity by approximately 50%. However,
      screening of milk vat samples is unlikely to be useful in countries with low
      prevalences of M. bovis in cattle and large herd sizes.

PMID- 24132606
TI  - EZH2 regulates cancer cell migration through repressing TIMP-3 in non-small cell
      lung cancer.
AB  - Histone methylations play important roles in human cancer metastasis. Enhancer of
      zeste homolog 2 (EZH2) is a key component of the polycomb repressor complex 2,
      which is responsible for histone H3K27 methylation. EZH2 is overexpressed in lung
      cancer and epigenetically silences tumor suppressor genes. Here, we showed that
      EZH2 was up-regulated in lung cancer and had a positive correlation with
      pathologic stage, nodal involvement in lung cancer patients. Moreover,
      overexpression of EZH2 was correlated with reduced tissue inhibitor of
      metalloproteinase-3 (TIMP-3) expression, which was shown to be negatively
      associated with tumor metastasis. Of note, overall survival time of patients with
      high EZH2/low TIMP-3 expression was significantly shorter than that of patients
      with low EZH2/high TIMP-3 (P = 0.031). RNA interfering and pharmacologic
      inhibition of EZH2 reduced histone H3 lysine 27 tri-methylation level and
      increased TIMP-3 expression level. Knockdown of EZH2 by siRNA significantly
      reduced A549 cancer cell migration. In contrast, reduction of TIMP-3 in A549
      cells partially rescued EZH2 deficiency-induced loss of cell migration capacity.
      Taken together, our findings indicate that EZH2 accelerates cancer cell
      migration, in part, via the repression of TIMP-3 expression, suggesting a
      potential mechanism by which EZH2 promotes lung cancer progression and
      metastasis.

PMID- 24132607
TI  - Expression of TMPRSS4 in patients with salivary adenoid cystic carcinoma:
      correlation with clinicopathological features and prognosis.
AB  - Although there is growing evidence supporting the hypothesis that TMPRSS4 is
      linked with cancer susceptibility, the precise role of TMPRSS4 expression in
      salivary adenoid cystic carcinoma (SACC) is still unknown. The aim of this study
      was to examine TMPRSS4 expression in SACC and determine its associations with
      clinicopathological features and survival. TMPRSS4 expression in 125 SACC tissue
      and adjacent non-cancerous tissues was analyzed by immunohistochemistry and
      Western blotting. In addition, the correlation of TMPRSS4 expression with
      clinicopathological variables was evaluated. The prognostic value of TMPRSS4 for
      overall survival (OS) and disease-free survival (DFS) was determined by Kaplan
      Meier estimates, and the significance of differences between curves was evaluated
      by the log-rank test. We found that high TMPRSS4 expression was predominantly
      observed in SACC tissues, but not in the adjacent normal salivary gland tissues.
      High TMPRSS4 expression in SACC tissues was correlated significantly with tumor
      TNM stage (P = 0.016), lymph node metastasis (P = 0.002) and distant metastasis
      (P < 0.001). While high TMPRSS4 expression was associated with poor OS (P =
      0.019) and DFS (P = 0.031), Cox regression analysis also revealed that TMPRSS4
      was an independent predictor of OS and DFS. These findings suggested that TMPRSS4
      was involved in the pathogenesis of SACC and might indicate a poor prognosis for
      SACC patients.

PMID- 24132612
TI  - [Psycho-oncological care for melanoma patients: conception and implementation].
AB  - Offering psycho-oncological care is an essential, guideline-based component of
      comprehensive care in skin cancer centers. This paper describes the development,
      implementation and utilization of a specific psycho-oncologic care concept for
      melanoma patients in the University Dermatology Clinic Freiburg. Based on the
      stepped-care principle, the concept is composed of interdisciplinary group
      sessions for patients and their relatives offered every 4-6 weeks addressing
      medical and psycho-oncological topics related to treatment of malignant melanoma
      and then individual psycho-oncological sessions modified for the patient's
      treatment needs. Between April 2010 and July 2012, 67 % of the melanoma patients
      treated in the Freiburg Skin Cancer Center were reached by the program. A stepped
      care concept with a routinely initiated first contact and low-threshold patient
      education group sessions is a reliable approach to reach patients and inform them
      about further psycho-oncological care. The advantages justify the allocation of
      resources and the approach proved successful for routine clinical practice.

PMID- 24132613
TI  - Incretin therapy for type 2 diabetes in Spain: a cost-effectiveness analysis of
      liraglutide versus sitagliptin.
AB  - INTRODUCTION: Treatment with glucagon-like peptide-1 receptor agonists and
      dipeptidyl peptidase-4 inhibitors, which target the incretin axis, has the
      potential to improve glycemic control in type 2 diabetes patients without the
      weight gain associated with traditional therapies. To evaluate the relative cost
      effectiveness of incretin therapies, the present study aimed to compare the long
      term clinical and cost implications associated with liraglutide and sitagliptin
      in type 2 diabetes patients in Spain. METHODS: Data were taken from a randomized,
      controlled trial (NCT00700817) in which adults with type 2 diabetes failing
      metformin monotherapy were randomly allocated to receive either liraglutide 1.2
      mg or sitagliptin 100 mg daily in addition to metformin. Long-term projections of
      clinical outcomes and direct costs (2012 EUR) based on observed treatment effects
      were made using a published and validated type 2 diabetes model. Costs were taken
      from published sources. Future costs and clinical benefits were discounted at 3%
      annually. Sensitivity analyses were performed. RESULTS: Liraglutide was
      associated with improved discounted life expectancy (14.05 versus 13.91 years)
      and quality-adjusted life expectancy [9.04 versus 8.87 quality-adjusted life
      years (QALYs)] compared to sitagliptin. Improved clinical outcomes were driven by
      improved glycemic control, leading to reduced incidence of diabetes-related
      complications, including renal disease, cardiovascular disease, ophthalmic and
      diabetic foot complications. Liraglutide was associated with increased direct
      costs of EUR 2,297, yielding an incremental cost-effectiveness ratio of EUR
      13,266 per QALY gained versus sitagliptin. CONCLUSIONS: Liraglutide was projected
      to improve life expectancy, quality-adjusted life expectancy and reduce incidence
      of diabetes-related complication. Liraglutide is likely to be cost-effective
      versus sitagliptin from a healthcare payer perspective in Spain.

PMID- 24132614
TI  - Increased risk of litigation associated with laser surgery by nonphysician
      operators.
AB  - IMPORTANCE: Controversy exists regarding the role of nonphysicians performing
      laser surgery and the increased risk of injury associated with this practice.
      OBJECTIVE: To identify the incidence of medical professional liability claims
      stemming from cutaneous laser surgery performed by nonphysician operators (NPOs).
      DESIGN, SETTING, AND PARTICIPANTS: Search of an online national database of
      public legal documents involving laser surgery by NPOs. EXPOSURE: Laser surgery
      by nonphysicians. MAIN OUTCOMES AND MEASURES: Frequency and nature of cases,
      including year of litigation, certification of provider and operator, type of
      procedure performed, clinical setting of injury, and cause of legal action.
      RESULTS: From January 1999, to December 2012, we identified 175 cases related to
      injury secondary to cutaneous laser surgery. Of these, 75 (42.9%) were cases
      involving an NPO. From 2008 to 2011, the percentage of cases with NPOs increased
      from 36.3% to 77.8%. Laser hair removal was the most commonly performed
      procedure. Despite the fact that approximately only one-third of laser hair
      removal procedures are performed by NPOs, 75.5% of hair removal lawsuits from
      2004 to 2012 were performed by NPOs. From 2008 to 2012, this number increased to
      85.7%. Most cases (64.0%) by NPOs were performed outside of a traditional medical
      setting. CONCLUSIONS AND RELEVANCE: Claims related to cutaneous laser surgery by
      NPOs, particularly outside of a traditional medical setting, are increasing.
      Physicians and other laser operators should be aware of their state laws,
      especially in regard to physician supervision of NPOs.

PMID- 24132615
TI  - Intramedullary gangliogliomas: clinical features, surgical outcomes, and
      neuropathic scoliosis.
AB  - Intramedullary spinal cord gangliogliomas are rare tumors composed of glial
      components and ganglion cells. These gangliogliomas are generally considered as
      slow-growing tumors, corresponding histologically to WHO grade I or II. There are
      few reports of large case series of intramedullary spinal cord gangliogliomas
      from a single center. We retrospectively reviewed a consecutive series of 18
      patients with pathologically diagnosed ganglioglioma. Clinical manifestations,
      radiological features, treatment and follow-up data, and concomitant scoliosis
      were investigated. The mean age at diagnosis was 27.5 years, with a slight female
      predominance. The primary clinical symptoms were sensorimotor deficits. Magnetic
      resonance (MR) imaging manifestations varied considerably. Some associated, but
      not necessary, features were found, such as young age at onset, large tumor
      dimension, and bony changes. Scoliosis was observed in seven patients. Remnant
      tumor progression was observed in five patients during the follow-up period, and
      no deaths occurred. The last neurological evaluation showed functional
      improvement from preoperative status in five patients. Differential diagnosis of
      ganglioglioma based on MR images alone is challenging, but the combination of
      some characteristic features can be helpful. An accurate diagnosis of
      ganglioglioma depends on pathological criteria. Despite the benign course of
      ganglioglioma, considerable growth may affect its resectability and prognosis.
      The extent of resection should be meticulously planned, and the potential risk of
      recurrence and neurological deterioration should be evaluated. The concomitant
      scoliosis is noteworthy. 

PMID- 24132616
TI  - Investigation and management of abnormal peri-menopausal bleeding.
AB  - Abnormal peri-menopausal bleeding is a common clinical problem. Decisions to
      investigate if the menstrual disorders are related to an underlying pathology or
      represent physiologic changes are often complex especially as no clear guidance
      is available. The aim of this review is to present a summary of the current
      available evidence regarding the investigation tools used to evaluate women with
      abnormal uterine bleeding during menopausal transition and in the post-menopausal
      period. In this article, we focus mainly on the investigation and exclusion of
      endometrial carcinoma, as this represents the most common malignancy diagnosed. 

PMID- 24132617
TI  - Mesh implantation for pelvic organ prolapse improves quality of life.
AB  - PURPOSE: The use of alloplastic meshes for repair of female pelvic organ prolapse
      (POP) has recently been discussed for its indications and safety. Mesh exposure
      and chronic pelvic pain are among the risks that need to be addressed to the
      patients. The purpose of this prospective observational study is to investigate
      the effect of vaginal mesh implantation on pelvic floor-related quality of life
      (QoL). METHODS: 55 patients were included in this prospective multicenter study.
      A validated QoL questionnaire comprising items on prolapse symptoms and bladder,
      bowel and sexual function was used. QoL data were acquired before and 1 year
      after POP surgery. Patients underwent POP surgery with implantation of either
      Prolift(r) or Seratom(r) mesh. RESULTS: Quality of life scores improved
      significantly after surgery. Prolapse complaints were reduced from 4.43 to 0.26
      (p < 0.001), and bladder and bowel complaints improved from 3.03 to 1.46 (p <
      0.001) and from 1.93 to 1.60 (p < 0.01) at follow-up. Furthermore, the sexual
      function score improved from 2.31 to 1.12 postoperatively (p < 0.01). CONCLUSION:
      Despite the risks discussed for vaginal mesh repair, we observed a statistically
      significant improvement of pelvic floor-related quality of life of POP patients.

PMID- 24132618
TI  - Food and beverage policies and public health ethics.
AB  - Government food and beverage policies can play an important role in promoting
      public health. Few people would question this assumption. Difficult questions can
      arise, however, when policymakers, public health officials, citizens, and
      businesses deliberate about food and beverage policies, because competing values
      may be at stake, such as public health, individual autonomy, personal
      responsibility, economic prosperity, and fairness. An ethically justified policy
      strikes a reasonable among competing values by meeting the following criteria:
      (1) the policy serves important social goal(s); (2) the policy is likely to be
      effective at achieving those goal(s); (3) less burdensome options are not likely
      to be effective at achieving the goals; (4) the policy is fair. 

PMID- 24132619
TI  - New approaches in sensitive chiral CE.
AB  - CE has shown to have a big potential for chiral separations, with advantages such
      as high efficiency, high resolution, and low sample and reagents consumption.
      Nevertheless, when UV detection is employed, CE has some drawbacks, especially
      the low sensitivity obtained due to the short optical path length.
      Notwithstanding, sensitivity improvements can be achieved when different
      approaches are employed, such as sample treatment strategies (off-line or on
      line), in-capillary sample preconcentration techniques, and/or alternative
      detection systems to UV-Vis (such as fluorescence, conductimetry,
      electrochemiluminiscence, MS, etc.). This article reviews the most recent
      methodological and instrumental advances reported from June 2011 to May 2013 for
      enhancing the sensitivity in chiral analysis by CE. The sensitivity achieved for
      the enantioseparated analytes and the applications carried out using the
      developed methodologies are also summarized.

PMID- 24132621
TI  - Monitoring the load on a telemeterised vertebral body replacement for a period of
      up to 65 months.
AB  - PURPOSE: To determine the postoperative temporal course of the forces acting on a
      vertebral body replacement (VBR) for two well reproducible activities. METHODS: A
      telemeterised VBR was implanted in five patients. It allows the measurement of
      six load components. Implant loads were measured in up to 28 measuring sessions
      for different activities, including standing and walking. RESULTS: The
      postoperative temporal course of the resultant implant forces measured during
      standing and walking was similar in each patient, but the patterns varied
      strongly from patient to patient. In one patient, the forces decreased in the
      first year and then increased in the following 4 years. In another patient, the
      forces increased in the first few months and then decreased. In a third patient,
      the forces varied only slightly in the postoperative time. In two patients, there
      was a strong drop of the implant force in the first two postoperative months. The
      force was on average approximately 100 N or 71% higher for walking than for
      standing. CONCLUSIONS: The strong force reduction in the first 2 months is most
      likely caused by implant subsidence, and the force reduction over a period of
      more than 6 months is most likely caused by fusion of the vertebrae adjacent to
      the VBR. The short-term force increase could be attributed to bone atrophy at the
      index level, and the long-term force increase could be attributed to an increase
      in the thoracic spine kyphosis angle.

PMID- 24132620
TI  - High-density lipoprotein cholesterol levels in middle-school children:
      association with cardiovascular risk factors and lifestyle behaviors.
AB  - To examine factors associated with low high-density lipoprotein cholesterol (HDL
      C) levels among middle school children. HDL-C levels were the primary outcome of
      interest. A total of 1,104 middle-school children (mean age 11.6 years, 51.2%
      female) were included in this analysis, of whom 177 (16%) had an HDL-C level <=40
      mg/dL. More than half of those with low HDL-C were overweight or obese (62.2%)
      and had greater systolic and diastolic blood pressure, triglyceride (TRG) levels,
      and low-density lipoprotein cholesterol levels compared with children with an HDL
      C level >40 mg/dL. Among those with an HDL-C <= 40 mg/dL, 35% also had body mass
      index >=85% and TRG levels >=150 mg/dL. Exercise habits were significantly
      associated with HDL-C level, whereas sedentary behaviors, such as screen time,
      were not significantly associated with HDL-C level. Fruit and vegetable intake
      was also not significantly associated with HDL-C level. Children with low HDL-C
      levels are more likely to be overweight and to have other physiological
      indicators of increased cardiovascular risk. Further research is needed to
      determine if school-based interventions can result in long-term improvements in
      HDL-C.

PMID- 24132622
TI  - Endurance and fatigue characteristics in the neck muscles during sub-maximal
      isometric test in patients with cervical radiculopathy.
AB  - PURPOSE: The aim of the study was to compare myoelectric manifestation in neck
      muscle endurance and fatigue characteristics during sub-maximal isometric
      endurance test in patients with cervical radiculopathy and asymptomatic subjects.
      An additional aim was to explore associations between primary neck muscle
      endurance, myoelectric fatigability, and self-rated levels of fatigue, pain and
      subjective health measurements in patients with cervical radiculopathy. METHODS:
      Muscle fatigue in the ventral and dorsal neck muscles was assessed in patients
      with cervical radiculopathy and in an asymptomatic group during an isometric neck
      muscle endurance test in prone and supine. 46 patients and 34 asymptomatic
      subjects participated. Surface electromyography signals were recorded from the
      sternocleidomastoid, cervical paraspinal muscles and upper and middle trapezius
      bilaterally during the endurance test. Subjective health measurements were
      assessed with questionnaires. RESULTS: The results showed altered neck muscle
      endurance in several of the muscles investigated with greater negative median
      frequency slope, greater variability, side imbalance, lower endurance time and
      higher experience of fatigue among the cervical radiculopathy patients compared
      with healthy subjects. Endurance times were significantly lower in both prone and
      in supine positions between the patients compared to asymptomatic subjects.
      During the neck muscle endurance test, fatigues in the upper trapezius muscles
      during the prone test and in the sternocleidomastoid muscles during the supine
      test were of more importance than self-perceived pain, fatigue, disability and
      kinesiophobia in predicting neck muscle endurance (NME). CONCLUSION: NME testing
      in the primary neck muscles seems to be an important factor to take into
      consideration in rehabilitation.

PMID- 24132624
TI  - Differences between hepatocellular carcinoma and hepatitis B virus infection in
      patients with and without cirrhosis.
AB  - BACKGROUND: In patients with hepatitis B virus (HBV) infections, differences in
      hepatocellular carcinoma (HCC) between those with liver cirrhosis and those
      without cirrhosis have not been elucidated. The aim of this study was to compare
      clinicopathological characteristics and survival between noncirrhotic and
      cirrhotic patients and to determine prognostic factors for tumor recurrence after
      hepatectomy in patients with HBV and HCC. METHODS: Between 2005 and 2010, 441
      curative hepatectomies for HCC in patients with cirrhosis and 454 for HCC in
      patients without cirrhosis were performed. RESULTS: Cirrhotic patients had lower
      platelet counts, protein induced by vitamin K antagonist-II (PIVKA-II) levels,
      and tumor size than noncirrhotic patients. HCC differentiation in noncirrhotic
      patients was poorer than in cirrhotic patients. The 1-, 2-, and 3-year disease
      free survival rates were 72.0, 65.6, and 61.0% in noncirrhotic patients, and
      68.6, 56.5, and 51.5% in cirrhotic patients, respectively (P = 0.013). However,
      the 1-, 2-, and 3-year overall survival rates were 92.4, 85.5, and 81.7% in
      noncirrhotic patients, and 91.9, 86.1, and 82.4% in cirrhotic patients,
      respectively (P = 0.683). Risk factors for tumor recurrence in each group varied
      in multivariate analyses. Increased age, high platelet counts, microvascular
      invasion, serosal invasion, and intrahepatic metastasis predisposed to tumor
      recurrence in noncirrhotic patients, but elevated PIVKA-II and alkaline
      phosphatase levels, low serum albumin levels, portal vein invasion, intrahepatic
      metastasis, and tumor size were predisposing factors for recurrence in cirrhotic
      patients. CONCLUSIONS: The clinicopathologic characteristics and risk factors for
      tumor recurrence in cirrhotic and noncirrhotic HCC patients with HBV infection
      differ.

PMID- 24132625
TI  - The number of lymph nodes dissected in breast cancer patients influences the
      accuracy of prognosis.
AB  - BACKGROUND: Recent trials have suggested that axillary node dissection may not be
      warranted in some breast cancer patients with one to two positive nodes. Given
      that lymph node ratio (LNR; number of positive lymph nodes divided by the total
      examined) has been shown to be a significant prognostic factor, we sought to
      determine whether the number of nodes removed in this low risk population
      predicted survival. METHODS: The National Cancer Database is a comprehensive
      clinical surveillance resource capturing 70% of newly diagnosed malignancies in
      the United States; 309,216 breast cancer patients diagnosed between 1998 and
      2005, with tumors <=5 cm and one to two positive nodes, formed the cohort of
      interest. RESULTS: Median age at diagnosis was 57 (range 18-90) years. Median
      tumor size was 2 (range 0.1-5) cm; 215,382 patients (69.7%) had one positive
      node, and 93,834 (30.3%) had two. The median number of lymph nodes examined was
      11 (range 1-84). Patients were categorized into low (<=0.2), medium (0.21-0.65),
      or high (>0.65) LNR groups, with 228,822 (74%), 55,797 (18%), and 24,597 (8%)
      patients in each of these categories, respectively. Median follow-up was 54.1
      months. Median overall survival (OS) for low, intermediate, and high LNR was
      66.1, 61.1, and 56.5 months, respectively (p < 0.001). In a Cox model controlling
      for clinicopathologic and therapy covariates, LNR category remained a significant
      predictor of OS (p < 0.001). CONCLUSIONS: LNR is an independent predictor of OS
      in a low-risk population with one to two positive nodes and tumors <=5 cm.
      Therefore, the number of lymph nodes excised may influence prognostic
      stratification.

PMID- 24132626
TI  - Postoperative nomograms predictive of survival after surgical management of
      malignant tumors of the major salivary glands.
AB  - OBJECTIVES: The objective of this study was to create a nomogram predictive of
      survival in salivary gland cancer. METHODS: Clinical, tumor, and treatment
      characteristics were collected for 301 patients who underwent surgery for
      salivary gland cancer between 1985 and 2009 at Memorial Sloan Kettering Cancer
      Centre. Factors predictive of overall survival (OS) and cancer-specific survival
      (CSS) were determined by univariate analysis. Cox risk regression was used to
      model OS data. Competing risks regression was used for cancer-specific death.
      Deaths from other causes were treated as competing risks for cancer-specific
      death. Predictive nomograms for OS and CSS were then created using stepdown
      method to select predictors of outcome. RESULTS: The median age was 62 (range 9
      89) years. There were 156 (52%) males and 145 (48%) females. Five variables
      predictive for OS (age, clinical T4 stage, histological grade, perineural
      invasion, and tumor dimension) were used to generate a parsimonious model, and a
      nomogram was created to predict 10-year survival probability. The concordance
      index (CI) for this nomogram was 0.809. Five variables predictive for CSS
      (histological grade, perineural invasion, clinical T4 stage, positive nodal
      status, and status of margins) were used to generate a second nomogram predicting
      CSS. This nomogram had a CI of 0.856. Both nomograms were validated internally by
      assessing discrimination and calibration. CONCLUSIONS: We have developed the
      first nomograms to predict prognosis in an individual patient with salivary gland
      cancer.

PMID- 24132623
TI  - Exploiting functional domains of GRK2/3 to alter the competitive balance of pro-
      and anticontractile signaling in airway smooth muscle.
AB  - To clarify the potential utility of targeting GRK2/3-mediated desensitization as
      a means of manipulating airway smooth muscle (ASM) contractile state, we assessed
      the specificity of GRK2/3 regulation of procontractile and relaxant G-protein
      coupled receptors in ASM. Functional domains of GRK2/3 were stably expressed, or
      siRNA-mediated GRK2/3 knockdown was performed, in human ASM cultures, and agonist
      induced signaling was assessed. Regulation of contraction of murine tracheal
      rings expressing GRK2 C terminus was also assessed. GRK2/3 knockdown or
      expression of the GRK2 C terminus caused a significant (~ 30-90%) increase in
      maximal beta-agonist and histamine [phosphoinositide (PI) hydrolysis] signaling,
      without affecting the calculated EC50. GRK2 C-terminal expression did not affect
      signaling by methacholine, thrombin, or LTD4. Expression of the GRK2 N terminus
      or kinase-dead holo-GRK2 diminished (~ 30-70%) both PI hydrolysis and Ca(2+)
      mobilization by every Gq-coupled receptor examined. Under conditions of GRK2 C
      terminal expression, beta-agonist inhibition of methacholine-stimulated PI
      hydrolysis was greater. Finally, transgenic expression of the GRK2 C terminus in
      murine ASM enabled ~ 30-50% greater beta-agonist-mediated relaxation of
      methacholine-induced contraction. Collectively these data demonstrate the
      relative selectivity of GRKs for the beta2AR in ASM and the ability to exploit
      GRK2/3 functional domains to render ASM hyporesponsive to contractile agents
      while increasing responsiveness to bronchodilating beta-agonist.

PMID- 24132627
TI  - High expression of interleukin-22 and its receptor predicts poor prognosis in
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The cytokine interleukin-22 (IL-22) and its receptor are present in
      the tumor microenvironment. Their function in pancreatic ductal adenocarcinoma
      (PDAC) remains largely unknown. The goal of the present study was to measure the
      expression of IL-22 and IL-22R in PDAC and assess their relationship with
      clinicopathological features and prognosis. METHODS: The expression of IL-22 and
      IL-22R was evaluated by immunohistochemistry in PDAC tissues from 57 patients and
      by Western blotting in six tumors and adjacent nontumor tissues. A statistical
      analysis was conducted to assess the relationship between levels of expression,
      clinicopathological factors, and overall survival. In addition, the relationship
      between the expression of IL-22 and IL-22R and invasion was assessed by Western
      blotting and transwell assay with the PDAC cell lines PANC1 and BxPC3. RESULTS:
      Positive IL-22 staining was detected in PDAC tissues and adjacent nontumor
      tissues. Positive IL-22R staining was detected in PDAC cells. High expression of
      IL-22 and IL-22R correlated significantly with lymph node involvement. IL-22
      increased the phosphorylation of signal transducer and activator of
      transcription3, the expression of matrix metalloproteinase 9, and the invasion in
      PANC1 and BxPC3 cells in vitro while silencing of IL-22R RNA caused opposite
      effects. Most importantly, overall survival was significantly poorer in patients
      with high expression of IL-22 and IL-22R than in those with low expression.
      CONCLUSIONS: These findings reveal the positive role of IL-22 and IL-22R in
      invasion and metastasis in human PDAC. IL-22 and IL-22R may be suitable
      independent prognostic markers in PDAC.

PMID- 24132629
TI  - Prophylaxis of migraine in children.

PMID- 24132628
TI  - Novel oral anticoagulants versus warfarin therapy at various levels of
      anticoagulation control in atrial fibrillation--a cost-effectiveness analysis.
AB  - BACKGROUND: The decision as to whether to use more expensive novel oral
      anticoagulants (NOACs) or invest resources for quality improvement of warfarin
      therapy requires input from both clinical and economic analyses. OBJECTIVE: Cost
      effectiveness of NOACs compared to warfarin therapy at various levels of patient
      time in therapeutic range (TTR) in patients with atrial fibrillation was
      examined, from the healthcare provider's perspective. DESIGN, SUBJECTS AND
      INTERVENTION: A Markov model was used to compare life-long economic and treatment
      outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial
      fibrillation patients with CHADS2 scores of 2 or above. Model inputs were derived
      from clinical trials published in the literature. MAIN MEASURES: The outcome
      measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER).
      KEY RESULTS: Using United States Dollar (USD) 50,000 as the threshold of
      willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of
      warfarin therapy was 60 % or below, or monthly cost of warfarin management
      increased by two-fold or more to achieve 70 % TTR. Warfarin therapy was cost
      effective when TTR of warfarin was 70 % with up to a 1.5-fold increment in
      monthly cost of care, or when TTR reached 75 % with monthly cost of warfarin care
      increased up to three-fold. At TTR 60 %, 70 % and 75 %, NOACs was cost-effective
      when monthly drug cost was < USD 200, < USD 122-185 and < USD 85-145,
      respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective
      83.6 %, 50.7 % and 32.7 % of the time at TTR of 60 %, 70 % and 75 %,
      respectively. CONCLUSIONS: The acceptance of NOACs as cost-effective was highly
      dependent upon drug cost, anticoagulation control for warfarin, and
      anticoagulation service cost.

PMID- 24132630
TI  - Editorial: the fear factor and forbidden facts.

PMID- 24132634
TI  - Engineering the emergence of stem cell therapeutics.

PMID- 24132635
TI  - Going with the flow: from circulating tumor cells to DNA.
AB  - Molecular analyses of circulating tumor DNA (ctDNA) in plasma from cancer
      patients have the potential to deliver minimally invasive diagnostic and disease
      monitoring biomarkers. Drawing from experience gained through the translation of
      circulating tumor cell detection to clinical tests, we discuss ctDNA as a source
      of tumor material for biomarker development. 

PMID- 24132636
TI  - Inhibition of the cardiomyocyte-specific kinase TNNI3K limits oxidative stress,
      injury, and adverse remodeling in the ischemic heart.
AB  - Percutaneous coronary intervention is first-line therapy for acute coronary
      syndromes (ACS) but can promote cardiomyocyte death and cardiac dysfunction via
      reperfusion injury, a phenomenon driven in large part by oxidative stress.
      Therapies to limit this progression have proven elusive, with no major classes of
      new agents since the development of anti-platelets/anti-thrombotics. We report
      that cardiac troponin I-interacting kinase (TNNI3K), a cardiomyocyte-specific
      kinase, promotes ischemia/reperfusion injury, oxidative stress, and myocyte
      death. TNNI3K-mediated injury occurs through increased mitochondrial superoxide
      production and impaired mitochondrial function and is largely dependent on p38
      mitogen-activated protein kinase (MAPK) activation. We developed a series of
      small-molecule TNNI3K inhibitors that reduce mitochondrial-derived superoxide
      generation, p38 activation, and infarct size when delivered at reperfusion to
      mimic clinical intervention. TNNI3K inhibition also preserves cardiac function
      and limits chronic adverse remodeling. Our findings demonstrate that TNNI3K
      modulates reperfusion injury in the ischemic heart and is a tractable therapeutic
      target for ACS. Pharmacologic TNNI3K inhibition would be cardiac-selective,
      preventing potential adverse effects of systemic kinase inhibition. 

PMID- 24132638
TI  - mAbs and Ad-vectored IFN-alpha therapy rescue Ebola-infected nonhuman primates
      when administered after the detection of viremia and symptoms.
AB  - ZMAb is a promising treatment against Ebola virus (EBOV) disease that has been
      shown to protect 50% (two of four) of nonhuman primates (NHPs) when administered
      2 days post-infection (dpi). To extend the treatment window and improve
      protection, we combined ZMAb with adenovirus-vectored interferon-alpha (Ad-IFN)
      and evaluated efficacy in EBOV-infected NHPs. Seventy-five percent (three of
      four) and 100% (four of four) of cynomolgus and rhesus macaques survived,
      respectively, when treatment was initiated after detection of viremia at 3 dpi.
      Fifty percent (two of four) of the cynomolgus macaques survived when Ad-IFN was
      given at 1 dpi, followed by ZMAb starting at 4 dpi, after positive diagnosis. The
      treatment was able to suppress viremia reaching ~10(5) TCID50 (median tissue
      culture infectious dose) per milliliter, leading to survival and robust specific
      immune responses. This study describes conditions capable of saving 100% of EBOV
      infected NHPs when initiated after the presence of detectable viremia along with
      symptoms. 

PMID- 24132637
TI  - A blood-based proteomic classifier for the molecular characterization of
      pulmonary nodules.
AB  - Each year, millions of pulmonary nodules are discovered by computed tomography
      and subsequently biopsied. Because most of these nodules are benign, many
      patients undergo unnecessary and costly invasive procedures. We present a 13
      protein blood-based classifier that differentiates malignant and benign nodules
      with high confidence, thereby providing a diagnostic tool to avoid invasive
      biopsy on benign nodules. Using a systems biology strategy, we identified 371
      protein candidates and developed a multiple reaction monitoring (MRM) assay for
      each. The MRM assays were applied in a three-site discovery study (n = 143) on
      plasma samples from patients with benign and stage IA lung cancer matched for
      nodule size, age, gender, and clinical site, producing a 13-protein classifier.
      The classifier was validated on an independent set of plasma samples (n = 104),
      exhibiting a negative predictive value (NPV) of 90%. Validation performance on
      samples from a nondiscovery clinical site showed an NPV of 94%, indicating the
      general effectiveness of the classifier. A pathway analysis demonstrated that the
      classifier proteins are likely modulated by a few transcription regulators
      (NF2L2, AHR, MYC, and FOS) that are associated with lung cancer, lung
      inflammation, and oxidative stress networks. The classifier score was independent
      of patient nodule size, smoking history, and age, which are risk factors used for
      clinical management of pulmonary nodules. Thus, this molecular test provides a
      potential complementary tool to help physicians in lung cancer diagnosis. 

PMID- 24132639
TI  - Tumor-specific activation of an EGFR-targeting probody enhances therapeutic
      index.
AB  - Target-mediated toxicity constitutes a major limitation for the development of
      therapeutic antibodies. To redirect the activity of antibodies recognizing widely
      distributed targets to the site of disease, we have applied a prodrug strategy to
      create an epidermal growth factor receptor (EGFR)-directed Probody therapeutic-an
      antibody that remains masked against antigen binding until activated locally by
      proteases commonly active in the tumor microenvironment. In vitro, the masked
      Probody showed diminished antigen binding and cell-based activities, but when
      activated by appropriate proteases, it regained full activity compared to the
      parental anti-EGFR antibody cetuximab. In vivo, the Probody was largely inert in
      the systemic circulation of mice, but was activated within tumor tissue and
      showed antitumor efficacy that was similar to that of cetuximab. The Probody
      demonstrated markedly improved safety and increased half-life in nonhuman
      primates, enabling it to be dosed safely at much higher levels than cetuximab. In
      addition, we found that both Probody-responsive xenograft tumors and primary
      tumor samples from patients were capable of activating the Probody ex vivo.
      Probodies may therefore improve the safety profile of therapeutic antibodies
      without compromising efficacy of the parental antibody and may enable the wider
      use of empowered antibody formats such as antibody-drug conjugates and
      bispecifics. 

PMID- 24132640
TI  - Bottom-up and top-down visuomotor responses to action observation.
AB  - Action observation produces automatic "mirror" responses in the observers' motor
      system. However, in daily life, nonimitative actions are often required to be
      produced in response to others' acts, generating a conflict between automatic and
      voluntary responses. First, we used single-pulse transcranial magnetic
      stimulation (TMS) to assess the temporal dynamics of motor output in healthy
      volunteers preparing rule-based counter-imitative motor responses cued by
      different observed hand movements. Second, we applied the same paradigm after 1
      Hz repetitive TMS (rTMS) of the left posterior parietal cortex (PPC) and of the
      left dorsolateral prefrontal cortex (dlPFC). The results showed an early (150 ms
      from onset of visual stimuli) stimulus-driven mirror response that was followed
      by a later (300 ms) rule-based nonmirror response. rTMS applied to the PPC
      modulated only the early mirror response. Conversely, rTMS to the dlPFC modulated
      specifically the late rule-based motor response. The data indicate that a fast
      bottom-up process mediated by the dorsal visual stream produces automatic
      imitative responses. Arbitrary rule-based visuomotor associations are on the
      contrary mediated by a slower system, relying on the prefrontal cortex. The 2
      systems are mutually independent and compete for motor output in socially
      relevant situations only at a distal level. 

PMID- 24132641
TI  - A peptide antagonist of ErbB receptors, Inherbin3, induces neurite outgrowth from
      rat cerebellar granule neurons through ErbB1 inhibition.
AB  - ErbB receptors not only function in cancer, but are also key developmental
      regulators in the nervous system. We previously identified an ErbB1 peptide
      antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in
      vivo. In this study, we found that inhibition of ErbB1 kinase activity and
      activation of ErbB4 by NRG-1beta induced neurite extension, suggesting that ErbB1
      and ErbB4 act as negative and positive regulators, respectively, of the
      neuritogenic response. Inherbin3, inhibited activation not only of ErbB1 but also
      of ErbB4 in primary neurons, strongly induced neurite outgrowth in rat cerebellar
      granule neurons, indicating that this effect mainly was due to inhibition of
      ErbB1 activation. 

PMID- 24132642
TI  - A novel prolyl hydroxylase inhibitor protects against cell death after hypoxia.
AB  - Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent
      hydroxylation of proline residues by prolyl hydroxylases (PHDs). We recently
      developed a novel PHD inhibitor, TM6008, that suppresses the activity of PHDs,
      inducing continuous HIF-1alpha activation. In this study, we investigated how
      TM6008 affects cell survival after hypoxic conditions capable of inducing HIF
      1alpha expression and how TM6008 regulates PHDs and genes downstream of HIF
      1alpha. After SHSY-5Y cells had been subjected to hypoxia, TM6008 was added to
      the cell culture medium under normoxic conditions. Apoptotic cell death was
      significantly augmented just after the hypoxic conditions, compared with cell
      death under normoxic conditions. Notably, when TM6008 was added to the media
      after the cells had been subjected to hypoxia, the expression level of HIF-1alpha
      increased and the number of cell deaths decreased, compared with the results for
      cells cultured in media without TM6008 after hypoxia, during the 7-day incubation
      period under normoxic conditions. Moreover, the protein expression levels of heme
      oxygenase 1, erythropoietin, and glucose transporter-3, which were genes
      downstream of HIF-1alpha, were elevated in media to which TM6008 had been added,
      compared with media without TM6008, during the 7-day incubation period under
      normoxic conditions. However, the protein expression levels of PHD2 and p53 which
      suppressed cell proliferation were suppressed in the media to which TM6008 had
      been added. Thus, TM6008, which suppresses the protein expressions of PHD2 and
      p53, might play an important role in cell survival after hypoxic conditions, with
      possible applications as a new compound for treatment after ischemic stroke. 

PMID- 24132644
TI  - Development and validation of an LC-ESI-MS/MS method for the quantitation of
      hemslecin A in rhesus monkey plasma and its application in pharmacokinetics.
AB  - In this study, a new LC-ESI-MS/MS-based method was validated for the quantitation
      of hemslecin A in rhesus monkey plasma using otophylloside A as internal standard
      (IS). Hemslecin A and the IS were extracted from rhesus monkey plasma using
      liquid-liquid extraction as the sample clean-up procedure, and were subjected to
      chromatography on a Phenomenex Luna CN column (150 * 2.0 mm, 3.0 um) with the
      mobile phase consisting of methanol and 0.02 mol/mL ammonium acetate (55:45, v/v)
      at a flow rate of 0.2 mL/min. Detection was performed on an Agilent G6410B tandem
      mass spectrometer by positive ion electrospray ionization in multiple reaction
      monitoring mode, monitoring the transitions m/z 580.5 [M + NH4 ](+)  -> 503.4 and
      m/z 518.2 [M + NH4 ](+)  -> 345.0 for hemslecin A and IS, respectively. The assay
      was linear over the concentration range of 0.5-200 ng/mL and was successfully
      applied to a pharmacokinetic study in rhesus monkeys.

PMID- 24132643
TI  - EZH2-miR-30d-KPNB1 pathway regulates malignant peripheral nerve sheath tumour
      cell survival and tumourigenesis.
AB  - Malignant peripheral nerve sheath tumours (MPNSTs), which develop sporadically or
      from neurofibromatosis, recur frequently with high metastatic potential and poor
      outcome. The polycomb group protein enhancer of zeste homologue 2 (EZH2) is an
      important regulator for various human malignancies. However, the function of EZH2
      in MPNSTs is unknown. Here we report that the EZH2-miR-30d-KPNB1 signalling
      pathway is critical for MPNST tumour cell survival in vitro and tumourigenicity
      in vivo. Up-regulated EZH2 in MPNST inhibits miR-30d transcription via promoter
      binding activity, leading to enhanced expression of the nuclear transport
      receptor KPNB1 that is inhibited by miR-30d targeting of KPNB1 3' UTR region.
      Furthermore, inhibition of EZH2 or KPNB1, or miR-30d over-expression, induces
      MPNST cell apoptosis in vitro and suppresses tumourigenesis in vivo. More
      importantly, forced over-expression of KPNB1 rescues MPNST cell apoptosis induced
      by EZH2 knockdown. Immunohistochemical analyses show that EZH2 and KPNB1 over
      expression is observed in human MPNST specimens and is negatively associated with
      miR-30d expression. Our findings identify a novel signalling pathway involved in
      MPNST tumourigenesis, and also suggest that EZH2-miR-30d-KPNB1 signalling
      represents multiple potential therapeutic targetable nodes for MPNST.

PMID- 24132645
TI  - Atrial fibrillation in heart failure: catheter and surgical interventional
      therapies.
AB  - Atrial fibrillation and heart failure commonly coexist in the same patient. Each
      may adversely affect the other. Atrial fibrillation leads to heart failure
      exacerbation, left ventricular function deterioration and an increase in thrombo
      embolic risk. Therapeutic options targeting atrial fibrillation in heart failure
      patients include pharmacological and non-pharmacological means. Pharmacological
      therapy is directed at either rate control using nodal blocking agents or rhythm
      control using anti-arrhythmic agents, of which the options are limited in
      patients with heart failure. The landmark AF-CHF trial did not show any benefit
      of rhythm control strategy as opposed to rate control in patients with heart
      failure and atrial fibrillation. However, patients in this trial as well as in
      others used mostly amiodarone for rhythm control. This might have negated any
      positive effects of achieving normal sinus rhythm. Non-pharmacological therapy
      both for rate and rhythm control is appealing. This includes AV node ablation for
      rate control, catheter ablation of atrial fibrillation and surgical therapy of
      atrial fibrillation. This review will address non-pharmacologic treatment of AF
      in heart failure patients. 

PMID- 24132646
TI  - Alterations in streaming potential in presence of time periodic pressure-driven
      flow of a power law fluid in narrow confinements with nonelectrostatic ion-ion
      interactions.
AB  - We study the coupled effect of electrokinetic phenomena and fluid rheology in
      altering the induced streaming potential in narrow fluidic confinements, which is
      manifested by establishing a time periodic pressure-driven flow in presence of
      electrical double layer phenomenon. However, in sharp contrast with reported
      literature, we take into account nonelectrostatic ion-ion interactions toward
      estimating the same in addition to electrostatic interactions and steric effects.
      We employ power law based rheological model for estimating the induced streaming
      potential. We bring out an intricate interaction between nonelectrostatic
      interactions and fluid rheology on the concerned electrokinetic phenomena,
      bearing immense consequences toward designing of integrated lab-on-a-chip-based
      microdevices and nanodevices. 

PMID- 24132647
TI  - Contrast enhanced ultrasound (CEUS) characterization of grey-scale sonographic
      indeterminate focal liver lesions in pediatric practice.
AB  - PURPOSE: To determine the usefulness of contrast-enhanced ultrasound (CEUS) in
      characterizing grey-scale sonographic indeterminate focal liver lesions (FLL) in
      pediatric practice. MATERIALS AND METHODS: Local Ethics Board approval waiver was
      attained. Consent for CEUS examinations was acquired from parents. Forty-four
      children referred for CEUS assessment of grey-scale sonographic indeterminate FLL
      over a 5-year period underwent standard multiphase CEUS performed by experienced
      operators. A phospholipid microbubble agent was used and low mechanical index
      ultrasound imaging techniques employed. Interpretation by consensus of the CEUS
      examination was compared to consensus interpretation of other imaging and to
      histology. Follow-up imaging was used to confirm stability of benign
      abnormalities. Any contrast reactions were recorded. RESULTS: The CEUS
      examination interpretation agreed with reference imaging in 29/34 (85.3 %) of
      cases. In discordant cases, reference imaging showed no abnormality (n = 5), with
      fatty change (n = 4) and regenerating nodules (n = 1) on CEUS and follow-up
      sonography. Where reference imaging was not performed (n = 10), histology (n = 7)
      or follow-up sonography (n = 3) confirmed the diagnosis. In one discordant case,
      all imaging modalities showed concordance identifying a malignant lesion; however
      histology demonstrated a benign hepatocellular adenoma. The specificity was 98.0
      % (95 % CI; 86 - 100 %) and the negative predictive value was 100 %. No adverse
      effects to the contrast material were noted. CONCLUSION: These findings
      demonstrate the usefulness of CEUS in characterizing indeterminate grey-scale
      sonography FLL in pediatric patients with the potential to reduce exposure to
      ionizing radiation.

PMID- 24132648
TI  - Early prediction of treatment response to sorafenib with elastosonography in a
      mice xenograft model of hepatocellular carcinoma: a proof-of-concept study.
AB  - PURPOSE: Sorafenib is the reference therapy for advanced hepatocellular carcinoma
      (HCC). There is no method for predicting in the early period subsequent
      individual response. Starting from the clinical experience in humans that
      subcutaneous metastases may rapidly change consistency under sorafenib and that
      elastosonography allows assessment of tissue elasticity, we investigated the role
      of this ultrasound-based technique in the early prediction of tumor response to
      sorafenib in a HCC mice model. MATERIALS AND METHODS: HCC subcutaneous
      xenografting in mice was utilized. Mice were randomized to vehicle (17 mice) or
      treatment with sorafenib (19 mice). Strain elastosonography (Esaote, Italy) of
      the tumor mass was performed at different time points (day 0, + 2 and + 14 from
      treatment start) until the mice were sacrificed (day + 14). At the same time
      points, the volume was calculated with ultrasonography. RESULTS: Sorafenib
      treated mice showed a smaller increase in tumor size on day + 14 in comparison to
      vehicle-treated mice (tumor volume increase + 175 % vs. + 382 %, p = 0.009). The
      median tumor elasticity increased in both groups on day + 2 (+ 5.65 % and + 3.86
      %, respectively) and decreased on day + 14 (-3.86 % and -3.63 %, respectively).
      However, among Sorafenib-treated tumors, 13 mice with a growth percentage delta <
      200 % (considered as good treatment response) showed an increase in elasticity on
      day + 2 (+ 8.9 %, range -12.6 - + 64) while the other 6 with a growth percentage
      delta > 300 % (considered as poor treatment response) showed a decrease in
      elasticity (-17 %, range -30.2 - + 15.3) (p = 0.044). CONCLUSION:
      Elastosonography appears to be a promising noninvasive new technique for the
      early treatment prediction of HCC tumor response to sorafenib. Specifically, an
      early increase in tumor elasticity (corresponding to tumors becoming softer) is
      associated with a good response.

PMID- 24132649
TI  - Monitoring during hepatic radiofrequency ablation (RFA): comparison of real-time
      ultrasound elastography (RTE) and contrast-enhanced ultrasound (CEUS): first
      clinical results of 25 patients.
AB  - PURPOSE: To evaluate the reliability of ultrasound elastography for delineating
      thermal ablation defects post-radiofrequency ablation (RFA) by comparing lesion
      dimensions determined by real-time elastography (RTE) with the findings of
      contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: A total of 21
      malignant liver tumors were percutaneously ablated using RFA. Color-coded
      elastography and CEUS were performed by one experienced examiner, using a 1 - 5
      MHz multi-frequency convex transducer (LOGIQ E9, GE). Lesions were examined using
      CEUS and real-time elastography (RTE) to assess ablation defects. Measurements of
      lesions (long axis, short axis, and area) representing the same image plane used
      for elastography were taken during CEUS examination and compared to the
      measurements obtained from the elastograms. All measurements were performed by
      two independent observers. RESULTS: A statistically significant correlation in
      vivo between RTE and CEUS measurements with respect to the lesion's principal
      axis and area (r = 0.876 long axis, r = 0.842 short axis and r = 0.889 area) was
      found. Inter-rater reliability assessed with the concordance correlation
      coefficient was substantial for all measurements (rhoc >= 0.96) Overall,
      elastography slightly underestimated the lesion size, as judged by the CEUS
      images. CONCLUSION: These results support that RTE could potentially be used for
      the routine assessment of thermal ablation therapies.

PMID- 24132650
TI  - Epigenetics components of aging in the central nervous system.
AB  - This review highlights recent discoveries that have shaped the emerging
      viewpoints in the field of epigenetic influences in the central nervous system
      (CNS), focusing on the following questions: (i) How is the CNS shaped during
      development when precursor cells transition into morphologically and molecularly
      distinct cell types, and is this event driven by epigenetic alterations?; ii) How
      do epigenetic pathways control CNS function?; (iii) What happens to "epigenetic
      memory" during aging processes, and do these alterations cause CNS dysfunction?;
      (iv) Can one restore normal CNS function by manipulating the epigenome using
      pharmacologic agents, and will this ameliorate aging-related neurodegeneration?
      These and other still unanswered questions remain critical to understanding the
      impact of multifaceted epigenetic machinery on the age-related dysfunction of
      CNS.

PMID- 24132651
TI  - The N-glycoform of sRAGE is the key determinant for its therapeutic efficacy to
      attenuate injury-elicited arterial inflammation and neointimal growth.
AB  - Signaling of the receptor for advanced glycation end products (RAGE) has been
      implicated in the development of injury-elicited vascular complications. Soluble
      RAGE (sRAGE) acts as a decoy of RAGE and has been used to treat pathological
      vascular conditions in animal models. However, previous studies used a high dose
      of sRAGE produced in insect Sf9 cells (sRAGE(Sf9))and multiple injections to
      achieve the therapeutic outcome. Here, we explore whether modulation of sRAGE N
      glycoform impacts its bioactivity and augments its therapeutic efficacy. We first
      profiled carbohydrate components of sRAGE produced in Chinese hamster Ovary cells
      (sRAGE(CHO)) to show that a majority of its N-glycans belong to sialylated
      complex types that are not shared by sRAGE(Sf9). In cell-based NF-kappaB
      activation and vascular smooth muscle cell (VSMC) migration assays, sRAGE(CHO)
      exhibited a significantly higher bioactivity relative to sRAGE(Sf9) to inhibit
      RAGE alarmin ligand-induced NF-kappaB activation and VSMC migration. We next
      studied whether this N-glycoform-associated bioactivity of sRAGE(CHO) is
      translated to higher in vivo therapeutic efficacy in a rat carotid artery balloon
      injury model. Consistent with the observed higher bioactivity in cell assays,
      sRAGE(CHO) significantly reduced injury-induced neointimal growth and the
      expression of inflammatory markers in injured vasculature. Specifically, a single
      dose of 3 ng/g of sRAGE(CHO) reduced neointimal hyperplasia by over 70%, whereas
      the same dose of sRAGE(Sf9) showed no effect. The administered sRAGE(CHO) is
      rapidly and specifically recruited to the injured arterial locus, suggesting that
      early intervention of arterial injury with sRAGE(CHO) may offset an inflammatory
      circuit and reduce the ensuing tissue remodeling. Our findings showed that the N
      glycoform of sRAGE is the key determinant underlying its bioactivity and thus is
      an important glycobioengineering target to develop a highly potent therapeutic
      sRAGE for future clinical applications. KEY MESSAGE: The specific N-glycoform
      modification is the key underlying sRAGE bioactivity Markedly reduced sRAGE dose
      to attenuate neointimal hyperplasia and inflammation Provide a molecular target
      for glycobioengineering of sRAGE as a therapeutic protein Blocking RAGE alarmin
      ligands during acute injury phase offsets neointimal growth.

PMID- 24132652
TI  - Time interval between primary radiotherapy and salvage laryngectomy: a predictor
      of pharyngocutaneous fistula formation.
AB  - Salvage laryngectomy (SL) is associated with high levels of morbidity. Rates of
      pharyngocutaneous fistulae (PCF) are as high as 35 % in some series. Patients at
      highest risk of such complications may be candidates for altered surgical
      management in terms of additional tissue transfer, or delayed tracheoesophageal
      puncture. This study investigates the relationship between the time from primary
      radiotherapy (RT) to salvage surgery and the development of PCF. 26 consecutive
      patients who underwent SL between 2000 and 2010 were identified from our
      institutional database. Demographic, staging, treatment and complication data
      were collected. Subgroup analysis was performed using the Student's t test or
      Mann-Whitney U test for continuous variables and either Chi-squared test or
      Fisher's Exact test for categorical variables. 26 patients underwent SL between
      October 2003 and July 2010. Of these, 15 (58 %) developed a PCF. On analysis of
      the time between pre-operative RT and surgery, a significant difference was seen,
      with a mean time of 19.5 months in those who developed a PCF versus 47.0 months
      in those who did not (p = 0.02). Patient characteristics, treatment, and
      pathology results were comparable between the two groups. There was no
      significant difference in distribution of the other covariates between the PCF
      and non-PCF groups. We reported a high rate of PCF and identified an association
      between PCF and a short time from primary treatment to salvage surgery.
      Identifying factors associated with higher rates of post-operative morbidity
      allows surgeons to adapt surgical planning in an attempt to minimize rates of
      PCF.

PMID- 24132653
TI  - Detection of bacterial biofilms in different types of chronic otitis media.
AB  - Biofilms are organized bacterial communities that may be homogeneous or
      heterogeneous. They play a significant role in the pathogenesis of chronic nasal
      sinusitis, chronic tonsillitis, cholesteatomas, and device-related infections.
      Despite this, few studies have been done that examine the presence of bacterial
      biofilms in tissues from patients with different types of COM or middle ear
      cholesteatomas. In the current study, we examined the presence of biofilms in
      surgical tissue specimens from humans with chronic ear infections using scanning
      electron microscopy (SEM). We hypothesize that bacterial biofilms present
      differently in patients with different types of chronic otitis media. Our results
      provide new insights regarding treatment of chronic otitis media. A prospective
      study was conducted in which middle ear tissues were obtained from 38 patients
      who underwent tympanoplasty and/or tympanomastoid surgery due to chronic ear
      infections. A total of 50 middle and mastoid tissue samples were processed for
      SEM analysis. In addition, 38 middle ear secretion specimens were obtained for
      routine bacterial culture analysis. Bacterial biofilms were present in 85 % (11
      of 13) of patients with middle ear cholesteatoma, 92 % (12/13) of patients with
      chronic otitis suppurative media (CSOM), and 16 % of patients (2/12) with
      tympanic membrane perforation (TMP). Fungal biofilms were found in two cases of
      cholesteatoma. The positive coincidence rate between bacterial biofilms
      visualized by SEM and bacteria detected by culture was 82 %. Our findings suggest
      that bacterial biofilms are very common in CSOM and middle ear cholesteatomas.
      Positive bacterial cultures imply the presence of biofilm formation in CSOM and
      cholesteatomas. As such, our results provide new insights regarding treatment of
      chronic otitis media.

PMID- 24132654
TI  - Risk factors for recurrent nerve palsy after thyroid surgery: a national study of
      patients treated at Danish departments of ENT Head and Neck Surgery.
AB  - Recurrent laryngeal nerve (RLN) injury is a well-known and serious complication
      to thyroid surgery. The objective was to estimate the frequency of post
      thyroidectomy RLN palsy and to identify possible risk factors. Based on the
      Danish national thyroid surgery database, 6,859 patients treated with thyroid
      surgery from 1 January 2001 to the 31 December 2008 at the Danish departments of
      ENT-HNS were analyzed. Unilateral RLN palsy was found in 2.1 % and bilateral in
      0.1 %. In benign histology, RLN palsies were registered in 1.3 %. Malignant
      histology and accordingly neck dissection were the most predominant risk factors
      with a relative risk (RR) of 5.4 and 5.8, respectively. In benign cases previous
      performed thyroid surgery had a RR of 10.4. High volume departments with more
      than 150 thyroid procedures per year seem to perform significantly better.
      Malignant histology, neck dissection and previous performed thyroid surgery are
      the strongest predictors for RLN palsy and patient information should be given
      accordingly. Incomplete resections should be reserved for isthmectomy only.
      Centralization of thyroid surgery in larger units might improve quality.

PMID- 24132655
TI  - Regenerative and proliferative activities of chondrocyte based on the degree of
      perichondrial injury in rabbit auricular cartilage.
AB  - Although the regeneration process for injured cartilage requires an intact
      perichondrium, few studies have addressed the importance of the intact
      perichondrial layer in the regeneration of damaged cartilage. In this study, we
      evaluated the role of the perichondrium on regenerative activities in injured
      cartilage according to different degrees of perichondrial injury. Auricular
      cartilage harvested from six New Zealand white rabbits was irradiated with a
      1,460-nm diode laser at two different power settings (0.3 or 0.5 W). Irradiated
      cartilage was reimplanted into a subperichondrial pocket under three different
      conditions: non-injured perichondrium (NPI), unilaterally injured perichondrium
      (UPI), or bilaterally injured perichondrium (BPI). Rabbits were sacrificed at 1,
      2, and 4 weeks after reimplantation and the auricular cartilage was reharvested.
      A histopathological study using hematoxylin and eosin staining, a live/dead
      viability assay, and immunohistochemical staining for proliferating cell nuclear
      antigen were performed to evaluate structural changes and regenerative and
      proliferative activities of the injured chondrocytes. A modified array and
      restored boundary of chondrocytes were observed in the NPI and UPI groups.
      Regeneration of chondrocytes was prominent in the NPI and UPI groups, but was not
      observed in the BPI group. Proliferative activity of chondrocytes was observed
      only when the perichondrium was preserved in the NPI and UPI groups. In contrast,
      proliferative activity was not observed until 4 weeks in the BPI group. The
      degree of perichondrial injury affected proliferation and regeneration in injured
      elastic cartilage. In the case of unilateral perichondrial injury, the surgeon
      should be careful to avoid damaging the other side of the perichondrium, because
      at least a unilateral perichondrial layer is needed for the regeneration of
      elastic cartilage. 

PMID- 24132656
TI  - Reversible posterior leukoencephalopathy syndrome.

PMID- 24132658
TI  - Hospital quality: does past performance predict future performance?

PMID- 24132657
TI  - Efficient and scalable expansion of human pluripotent stem cells under clinically
      compliant settings: a view in 2013.
AB  - Human pluripotent stem cells (hPSCs) hold great promise for revolutionizing
      regenerative medicine for their potential applications in disease modeling, drug
      discovery, and cellular therapy. Many their applications require robust and
      scalable expansion of hPSCs, even under settings compliant to good clinical
      practices. Rapid evolution of media and substrates provided safer and more
      defined culture conditions for long-term expansion of undifferentiated hPSCs in
      either adhesion or suspension. With well-designed automatic systems or fully
      controlled bioreactors, production of a clinically relevant quantity of hPSCs
      could be achieved in the near future. The goal is to find a scalable, xeno-free,
      chemically defined, and economic culture system for clinical-grade expansion of
      hPSCs that complies the requirements of current good manufacturing practices.
      This review provides an updated overview of the current development and
      challenges on the way to accomplish this goal, including discussions on basic
      principles for bioprocess design, serum-free media, extracellular matric or
      synthesized substrate, microcarrier- or cell aggregate-based suspension culture,
      and scalability and practicality of equipment.

PMID- 24132659
TI  - The possible interplanetary transfer of microbes: assessing the viability of
      Deinococcus spp. under the ISS Environmental conditions for performing exposure
      experiments of microbes in the Tanpopo mission.
AB  - To investigate the possible interplanetary transfer of life, numerous exposure
      experiments have been carried out on various microbes in space since the 1960s.
      In the Tanpopo mission, we have proposed to carry out experiments on capture and
      space exposure of microbes at the Exposure Facility of the Japanese Experimental
      Module of the International Space Station (ISS). Microbial candidates for the
      exposure experiments in space include Deinococcus spp.: Deinococcus radiodurans,
      D. aerius and D. aetherius. In this paper, we have examined the survivability of
      Deinococcus spp. under the environmental conditions in ISS in orbit (i.e., long
      exposure to heavy-ion beams, temperature cycles, vacuum and UV irradiation). A
      One-year dose of heavy-ion beam irradiation did not affect the viability of
      Deinococcus spp. within the detection limit. Vacuum (10(-1) Pa) also had little
      effect on the cell viability. Experiments to test the effects of changes in
      temperature from 80  degrees C to -80  degrees C in 90 min (+/- 80  degrees C/90
      min cycle) or from 60  degrees C to -60  degrees C in 90 min (+/- 60  degrees
      C/90 min cycle) on cell viability revealed that the survival rate decreased
      severely by the +/- 80  degrees C/90 min temperature cycle. Exposure of various
      thicknesses of deinococcal cell aggregates to UV radiation (172 nm and 254 nm,
      respectively) revealed that a few hundred micrometer thick aggregate of
      deinococcal cells would be able to withstand the solar UV radiation on ISS for 1
      year. We concluded that aggregated deinococcal cells will survive the yearlong
      exposure experiments. We propose that microbial cells can aggregate as an ark for
      the interplanetary transfer of microbes, and we named it 'massapanspermia'.

PMID- 24132660
TI  - A CHO/fibre diet reduces and a MUFA diet increases postprandial lipaemia in type
      2 diabetes: no supplementary effects of low-volume physical training.
AB  - The aim of the study was to evaluate the effects of a supervised physical
      training added to a healthy diet-rich in either carbohydrate and fibre
      (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia,
      an independent cardiovascular risk factor particularly relevant in type 2
      diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D,
      of both genders, in good blood glucose control with diet or diet+metformin, with
      normal fasting plasma lipids. According to a parallel groups 2 * 2 factorial
      design, participants were randomized to an 8-week isoenergetic intervention with
      a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic
      training programme. The main outcome of the study was the incremental area under
      the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL
      lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856).
      Body weight remained stable during the trial in all groups. Physical fitness
      slightly improved with training (VO2 peak, 16 +/- 4 vs. 15 +/- 3 ml/kg/min, M +/-
      SD, p < 0.05). Postprandial triglyceride and cholesterol iAUCs in plasma and
      chylomicron+VLDL fraction decreased after the CHO/fibre diet, but increased after
      the MUFA diet with a significant effect for diet by two-way ANOVA (p < 0.05). The
      addition of exercise training to either dietary intervention did not
      significantly influence postprandial lipid response. A diet rich in carbohydrates
      and fibre reduced postprandial triglyceride-rich lipoproteins compared with a
      diet rich in MUFA in patients with T2D. A supervised low-volume physical training
      did not significantly influence these dietary effects. 

PMID- 24132661
TI  - Modified Jiu Wei Qiang Huo decoction improves dysfunctional metabolomics in
      influenza A pneumonia-infected mice.
AB  - In order to study the effective mechanism of a traditional Chinese medicine
      (TCM), modified Jiu Wei Qiang Huo decoction (MJWQH), against H1N1-induced
      pneumonia in mice, we chose a holistic approach. A reverse-phase liquid
      chromatography with quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS) was
      developed to determine metabolomic biomarkers in mouse serum for the MJWQH
      effects. Thirteen biomarkers of H1N1-induced pneumonia in mice serum were
      identified, which comprised l-valine, lauroylcarnitine, palmitoyl-l-carnitine, l
      ornithine, uric acid, taurine, O-succinyl-l-homoserine, l-leucine, l
      phenylalanine, PGF2alpha, 20-ethyl-PGE2, arachidonic acid, and glycerophospho-N
      arachidonoyl ethanolamine. Among them, metabolites of amino acids, fatty acids
      and arachidonic acid had the most relevant changes in mice with H1N1-induced
      pneumonia. MJWQH effectively improved weight loss, lung index, biomarkers and
      inflammatory mediators such as prostaglandin E2 and phospholipase A2 in the
      infected mice. Importantly, MJWQH reversed the elevated biomarkers to the control
      levels from the infection, which provided a systematic view and a theoretical
      basis for its prevention or treatment. The results suggest that the protective
      effect of MJWQH against H1N1-induced pneumonia is possibly through regulation of
      pathways for amino acid, fatty acid and arachidonic acid metabolism. They also
      suggest that the LC-MS-based metabolomic strategy is a powerful tool for
      elucidation of the mechanisms of TCM.

PMID- 24132662
TI  - Endotoxin tolerance induced by lipopolysaccharides derived from Porphyromonas
      gingivalis and Escherichia coli: alternations in Toll-like receptor 2 and 4
      signaling pathway.
AB  - Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of
      the host to periodontal pathogens and their virulence factors induces a
      hyporesponsive state to subsequent challenge, which is termed endotoxin
      tolerance. In this experiment, we studied the cytokine production in THP-1 cells
      upon single or repeated Porphyromonas gingivalis (P. gingivalis)
      lipopolysaccharide (LPS) or Escherichia coli (E. coli) LPS stimulation by ELISA.
      In addition, the protein expression profiles of Toll-like receptor 2 (TLR2),
      TLR4, IL-1 receptor-associated kinase 4 (IRAK4) and IRAK-M and the gene
      expression changes of Toll-interacting protein (Tollip) and suppressor of
      cytokine-signaling-1 (SOCS1) were explored to identify possible mechanisms for
      changes in cytokine secretion. After repeated stimulation with P. gingivalis LPS
      or E. coli LPS, secretions of TNF-alpha and IL-1beta were decreased significantly
      compared with those following single challenge, while the levels of IL-10 were
      increased (p < 0.05). Only comparable levels of IL-8 were confirmed in P.
      gingivalis LPS-tolerized cells (p > 0.05). In addition, severe downregulation of
      TLR2 was detected in THP-1 cells retreated with P. gingivalis LPS, and the
      reduction of TLR4 expression was observed in cells restimulated with E. coli LPS
      (p < 0.05). Precondition with P. gingivalis LPS or E. coli LPS also led to an
      enhancement of IRAK-M and SOCS1, while maintaining the expressions of IRAK4 and
      Tollip. This pattern of cytokine production indicates the different effects of
      endotoxin tolerance triggered by P. gingivalis LPS and E. coli LPS, which might
      contribute to limiting inflammatory damage. Moreover, TLR2, TLR4, IRAK-M, and
      SOCS1 might play important roles in developing tolerance.

PMID- 24132664
TI  - Culture cultivating culture: the four products of the meaning-made world.
AB  - Culture, in a semiotic cultural psychology, is defined from the viewpoint of
      cultivation--the meaning making processes that give meaning to the world
      (Valsiner 2000, 2007a). However, the individual is not simply a process-machine
      in an empty world--there are both the external outcomes of meaning making
      (individual and group based) as well as the collective influence on the
      cultivation process. I argue to examine the cultivation process more completely,
      one must look at these external influences that catalyze future cultivation
      processes. By examining the power of the external (environmental Umwelten) and
      group-internal (myths, morals), a much greater understanding of the behavior of
      individuals can be accomplished beyond examining the individual's process of
      meaning making. Further work into examining the objects that affectively activate
      the individual as well as group action and meaning making is called for and
      examples of such studies are given.

PMID- 24132663
TI  - Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with
      methyleneindolinones.
AB  - Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with
      methyleneindolinones are reported. The spiro[pyrazolin-3,3'-oxindole] products
      are formed in good yields (up to 98%) and high enantioselectivity (up to 99% ee).

PMID- 24132665
TI  - Outcomes in patients with mucosal melanomas.
AB  - BACKGROUND AND OBJECTIVE: Our goal was to evaluate the different subtypes of
      mucosal melanoma and describe specific variables that predict outcomes. METHODS:
      Prospective review of two tertiary care center databases identified 76 mucosal
      melanoma patients; 73 with complete records were included. Demographic and
      clinical data were analyzed. Cox regression determined variables impacting
      recurrence and survival. RESULTS: In the 73 patients, the mean age was 64 years,
      and 74% were female. Sixty-seven percent presented with lymph node involvement,
      and 73% had ulcerated tumors. Major sites affected were nasal/palate/oral (36%),
      vulvar/vaginal/cervical (48%), and anorectal (15%). Mean overall and disease-free
      survival were 56.9 and 27.2 months. Variables associated with decreased survival
      included: lymphovascular invasion (HR17.70, P = 0.0093), Caucasian race (HR3.02,
      P = 0.0362), nasal/palate/oral sub-group (HR1.85, P = 0.026), Breslow thickness
      (HR1.23, P = 0.00004), T stage (HR1.34, P = 0.0075), M stage (HR3.03, P =
      0.0039), and chemotherapy (HR3.13, P = 0.0002). The worst prognosis was seen in
      the nasal/palate/oral sub-group, with a median overall survival of 9.7 months and
      recurrence-free time of 4.5 months. This subtype also demonstrated high lymph
      node positivity, ulceration, and larger tumor size. CONCLUSION: The nasal,
      palate, oral subtype has the worst prognosis compared to other mucosal melanoma
      locations. Studies are ongoing to evaluate pathologic and genomic variables that
      may predict outcomes.

PMID- 24132667
TI  - Cellodextrin transporters play important roles in cellulase induction in the
      cellulolytic fungus Penicillium oxalicum.
AB  - Cellodextrin transporters (cellodextrin permeases) have been identified in fungi
      in recent years. However, the functions of these transporters in cellulose
      utilization and cellulase expression have not been well studied. In this study,
      three cellodextrin transporters, namely, CdtC, CdtD, and CdtG, in the
      cellulolytic fungus Penicillium oxalicum (formally was classified as P.
      decumbens) were identified, and their functions were analyzed. The deletion of a
      single cellodextrin transporter gene slightly decreased cellobiose consumption,
      but no observable effect on cellulase expression was observed, which was
      attributed to the overlapping activity of isozymes. Further simultaneous deletion
      of cdtC and cdtD resulted in significantly decreased cellobiose consumption and
      poor growth on cellulose. The extracellular activity and transcription level of
      cellulases in the mutant without cdtC and cdtD were significantly lower than
      those in the wild-type strain when grown on cellulose. This result provides
      direct evidence of the crucial function of cellodextrin transporters in the
      induction of cellulase expression by insoluble cellulose. 

PMID- 24132666
TI  - Antibacterial activity of the lipopetides produced by Bacillus amyloliquefaciens
      M1 against multidrug-resistant Vibrio spp. isolated from diseased marine animals.
AB  - In this work, the antibacterial activity of the lipopeptides produced by Bacillus
      amyloliquefaciens M1 was examined against multidrug-resistant Vibrio spp. and
      Shewanella aquimarina isolated from diseased marine animals. A new and cheap
      medium which contained 1.0 % soybean powder, 1.5 % wheat flour, pH 7.0 was
      developed. A crude surfactant concentration of 0.28 mg/ml was obtained after 18 h
      of 10-l fermentation and diameter of the clear zone on the plate seeded with
      Vibrio anguillarum was 34 mm. A preliminary characterization suggested that the
      lipopeptide N3 produced by B. amyloliquefaciens M1 was the main product and
      contained the surfactin isoforms with amino acids (GLLVDLL) and hydroxy fatty
      acids (of 12-15 carbons in length). The evaluation of the antibacterial activity
      of the lipopeptide N3 was carried out against S. aquimarina and nine species of
      Vibrio spp.. It was found that all the Vibrio spp. and S. aquimarina showed
      resistance to several different antibiotics, suggesting that they were the
      multidrug resistance. It was also indicated that all the Vibrio spp. strains and
      S. aquimarina were sensitive to the surfactin N3, in particular V. anguillarum.
      The results demonstrated that the lipopeptides produced by B. amyloliquefaciens
      M1 had a broad spectrum of action, including antibacterial activity against the
      pathogenic Vibrio spp. with multidrug-resistant profiles. After the treatment
      with the lipopeptide N3, the cell membrane of V. anguillarum was damaged, and the
      whole cells of the bacterium were disrupted.

PMID- 24132669
TI  - [Elective and acute procedures in trauma surgery. Complications requiring
      revision].
AB  - BACKGROUND: Using data between 2010 and 31 March 2012, a cohort study concerning
      complications of all discharged patients who had undergone surgery was performed.
      PATIENTS AND METHODS: In our detailed analysis, we defined two groups out of the
      5,248 cases: an acute trauma patient group (n = 3,942) and an elective patient
      group (n = 1,306). Complications were divided into the following groups: (1)
      technical complications (failure of the implant, poor indication, instability or
      non-union), (2) local complication (hematoma or delayed wound healing), and (3)
      infection. RESULTS: In 4.4% of patients (n = 233), treatment was delayed because
      of a complication. In 2.3% (n = 123), a technical complication was observed,
      followed by local complications in 1.3% [e.g., hematoma 0.6%, other wound healing
      disturbance (0.6%)]. In the elective surgery group, the percentage of
      complications needing revision (3.1%) was significantly lower compared to the
      trauma surgery group (4.9%). The patient's age for the non-complicated surgery
      group was significantly lower (54 vs. 63 years) and length of hospital stay (6.7
      days longer) was significantly higher in patients with complications. Risk
      factors such as smoking were significantly more frequent in patients with
      complications (9% vs. 18.5%). CONCLUSION: Recording and evaluating of
      complications in surgery plays a major role for quality control. Certain factors
      (e.g., comorbidity and the age of the patient) cannot be influenced, but
      complications caused by technical problems could theoretically be avoided.
      Especially these cases must be analyzed in detail to reduce the percentage of
      complications requiring revision.

PMID- 24132670
TI  - Pharmacokinetic study of Guanfu base G in rats by LC-ESI-MS.
AB  - A sensitive and simple liquid chromatography -: electrospray ionization mass
      spectrometry method has been established and validated for the quantification of
      Guanfu base G in rats. Phenoprolamine hydrochloride was selected as the internal
      standard. Sample preparation involved simple liquid-liquid extraction by
      ethylacetate with high efficiency. The chromatographical separation was performed
      on a Shimadzu C18 column (150 * 2.0 mm, 5 um) with a gradient elution of 0.2%
      acetic acid-acetonitrile (30:70, v/v). The method was sensitive with the lowest
      limit of detection at 1 ng/mL (S/N >= 3) in 100 uL of rat plasma. Good linearity
      (r = 0.9996) was obtained covering a concentration of 5-2000 ng/mL. The intra-
      and interday assay precision ranged from 4.3 to 6.1% and 5.4 to 8.3%,
      respectively. In addition, the stability, extraction recovery and matrix effect
      involved in the method were also validated. After intravenous dosing, rat plasma
      Guangfu base G (GFG) concentration declined in a biphasic manner with a terminal
      elimination half-life of 3.72 h. The total plasma clearance values were 1.15
      L/h/kg. After oral dosing, the plasma GFG concentration reached a maximum within
      0.5 h. The absolute bioavailability of GFG was 83.06%. 

PMID- 24132671
TI  - Epiretinal membrane: a treatable cause of visual disability in myotonic dystrophy
      type 1.
AB  - A wide range of ocular abnormalities have been documented to occur in patients
      with myotonic dystrophy type 1. The objectives of this study were to investigate
      the macular and optic nerve morphology using optical coherence tomography in
      patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1
      patients and 28 controls were recruited for participation. All participants
      underwent a thorough ophthalmologic examination, including spectral-domain
      optical coherence tomography of the macula and retinal nerve fibre layer. Images
      were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of
      the participants. Average macular thickness was significantly greater in the
      myotonic dystrophy group compared to controls [327.3 MUm vs. 308.5 MUm (p <
      0.001)]. Macular thickness was significantly greater (p < 0.005) in five of the
      nine macular regions. The increase in macular thickness was due to the increased
      prevalence of epiretinal membranes in the myotonic dystrophy patient group (p =
      0.0002): 48.2 % of myotonic dystrophy patient eyes had evidence of epiretinal
      membrane, compared with 12.5 % of control eyes. Examination revealed that 56.7 %
      of myotonic dystrophy patients had an epiretinal membrane in at least one eye.
      Visual acuity was reduced due to the presence of epiretinal membrane in six
      patient eyes and none of the control eyes. The presence of an epiretinal membrane
      was significantly correlated with increasing age in the patient group. We report
      an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1
      group. This may be a previously under-recognised form of visual impairment in
      this group. Epiretinal membranes can be treated surgically. We suggest that, in
      addition to a comprehensive clinical examination, optical coherence tomography
      examination is implemented as part of an ophthalmological assessment for the
      myotonic dystrophy type 1 patient with reduced visual acuity.

PMID- 24132672
TI  - Ocular flutter, generalized myoclonus, and truncal ataxia in a patient with
      Graves' ophthalmopathy.

PMID- 24132673
TI  - [A Mycotic Pulmonary Artery Aneurysm in an Intravenous Drug User].

PMID- 24132674
TI  - [Total-endoscopic Thyroid Resection in ABBA-Technique: Comments on the
      Integration of Intraoperative Neuromonitoring].
AB  - Background: Total endoscopic thyroid resections without any scars on the neck are
      a special challenge for the surgeon. Clinical results of intraoperative
      neuromonitoring (IONM) in the axillo-bilateral-breast-approach (ABBA) have not
      been described so far. Methods: 29 female patients (~ 40 years) were operated for
      one-sided thyroid pathology using the ABBA technique (20 subtotal resections, 9
      hemithyroidectomies). Suspected malignoma, size > 35 mL, known thyroiditis and
      recurrencies were excluded. For stimulation a 30-cm handprobe and for signal
      deviation a tube adhesive electrode (ISIS; Fa. Inomed, Emmendingen, Germany) were
      used. Results: The average operation time was 132 minutes. Intraoperative blood
      loss necessitated conversion to the open procedure in 1 case. A single tube
      electrode dislocation occurred. In the alternative a bipolar needle electrode was
      inserted percutaneously through the cricothyroid ligament. One intraoperative
      signal loss was confirmed by the laryngoscopic finding of vocal cord paresis,
      which recovered within 6 months. An additional case of incomplete brachial plexus
      paralysis was observed with a 2-day recovery time. Conclusion: Direct
      neuromonitoring of the recurrent laryngeal nerve can be easily applied in the
      total endoscopic ABBA technique for thyroid resection. Vagal stimulation, which
      is obligatory in open thyroid surgery, cannot consequently be included in this
      endoscopic operation method. Unexpected tube electrode dislocation may cause IONM
      misinterpretation. A risk of double-sided vocal cord palsy is theoretically
      present.

PMID- 24132675
TI  - [Clostridium difficile infection (CDI) in the course of time - an issue only for
      the internist?].
AB  - BACKGROUND: Toxigenic strains of Clostridium (C.) difficile are the most
      prevalent pathogens of antibiotic associated intestinal disease and nosocomial
      diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI)
      have increased worldwide. MATERIALS AND METHODS: With clinical and
      microbiological original data for 2002-2012 from the University Hospitals Leipzig
      and Halle (Saale), Germany, the authors illustrate the current situation
      regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest
      developments in terms of incidence, prevalence of resistance, diagnosis and
      treatment strategies regarding CDI with an emphasis on surgical options. RESULTS:
      Following the general trend, at the University Hospitals of Leipzig and Halle
      (Saale) there was also an increase in incidence of CDI, especially of severe
      clinical courses. In primary and secondary care facilities, prevention of CDI is
      based on hygiene management and restricted usage of antibiotics, preferably as
      "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic
      Fidaxomicin was approved in the European Union for the treatment of CDI. The
      therapeutic armamentarium, previously based on metronidazole or vancomycin, has
      now been enriched by a substance that presumably will reduce the rate of
      recurrence of CDI. Moreover, early data from case series and controlled trials
      suggest that the re-establishment of eubiosis in the colon of patients with
      recurrent CDI by stool transplantation from healthy donors is an alternative to
      antibiotics. Standard surgical intervention for refractory CDI is subtotal
      colectomy with terminal ileostomy. In patients with adequate life expectancy and
      without organ dysfunction, a colon-saving surgical technique should be
      considered. CONCLUSION: Taking antibiotics for most remains the main risk factor
      for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is
      hope for an improvement in the conservative treatment of CDI. Stool transplants
      from healthy donors are now considered to be better than giving antibiotics for
      severe CDI, but this treatment has not found broad acceptance yet. In cases with
      a lack of early treatment success, the surgeon must be consulted. Here, the
      evidence for preferably colon-saving surgical procedures is so far unfortunately
      low.

PMID- 24132676
TI  - [Surgical Instrument-Associated, Miniaturised Separate Light Source Facilitates
      Intraperitoneal Dissection in Laparoscopic Surgery, e.g., in Cholecystectomy -
      "Technical Note"].

PMID- 24132677
TI  - [Structured teaching of surgery the LMU model in Munich].
AB  - The medical curriculum (MeCuM) of the Ludwig Maximilian University (LMU) in
      Munich is a dynamic curriculum aimed to support the learning process of all
      students with their different learning styles. It is based on interactive,
      activating teaching methods in order to increase students' interest, and on
      repetitive evaluation of teaching units to modify the teaching in order to meet
      students' needs and wishes. In this context the teaching of surgery at our
      faculty takes place. Besides interdisciplinary lessons where diseases are taught
      in cooperation with our colleagues from internal medicine, indications for
      surgery, complications and consequences of surgery for the patients are analysed
      in PBL tutorials, online cases, bedside teachings and practical teaching on the
      ward. Surgical skills like suturing are demonstrated in videos, practiced on
      models or during practical teaching on the ward and they are tested in OSCEs.
      During the "praktisches Jahr", the students in the last year of their medical
      studies are supposed to apply their practical skills besides repeating
      theoretical knowledge in order to pass the final examination. For this purpose
      they are taught in a revision course called "LMU-StaR" (revision course for the
      Staatsexamen). In this paper we describe in detail the teaching of surgery at our
      faculty. 

PMID- 24132678
TI  - [Contrast-enhanced sonography and endoscopic ultrasound for the diagnosis of
      pancreatic diseases].
AB  - Contrast-enhanced ultrasound (CEUS) has increased the diagnostic spectrum of
      clinical ultrasound. Especially the introduction of specific contrast-enhanced
      software in connection with the development of second generation contrast
      enhancers has enabled the development of CEUS to a stage where it sometimes
      furnishes better diagnostic results than any other cross-sectional diagnostic
      imaging method. The present article should provide the reader with an overview
      about the diagnostic possibilities of CEUS including contrast-enhanced endoscopic
      ultrasound. The reader should then be able to understand the weaknesses and
      strengths of CEUS in the diagnostic apporach to pancreatic diseases. 

PMID- 24132679
TI  - [Hepatocellular carcinoma - current aspects of screening, surveillance and
      therapeutic strategies (revised EASL-EORTC recommendations)].
AB  - With an incidence of 523 000 new cases a year hepatocellular carcinomas (HCCs)
      belong to the most frequent cancer entities worldwide. Diagnostic and therapeutic
      procederes have been improved during the last years. Surveillance of patients
      with high risk factors leads to an early diagnosis. Up to now the detection of
      early HCCs represents the best prerequisite for any curative therapy. The present
      synopsis summarises the current guidelines of the European Association for the
      Study of the Liver (EASL) and the European Organisation for Research and
      Treatment of Cancer (EORTC) with a special focus on screening and surveillance of
      risk groups. 

PMID- 24132680
TI  - [Advances, limitations and prospects of oncological liver surgery].
AB  - Modern oncological liver surgery continues to push the limits of resectability by
      incorporating an array of new developments in the fields of surgery, anaesthesia
      and intensive care, oncology, radiology and transplantation medicine. New
      criteria for determining the resectability of primary and secondary liver tumours
      have been developed and introduced into national consensus guidelines. Modern
      tools for improving oncological outcome include the rapid induction of liver
      hypertrophy prior to major liver resection, downstaging of tumours with advanced
      chemotherapy protocols, minimally invasive local therapies like radiofrequency
      ablation and chemo- or radioembolisation, and liver transplantation for non
      resectable hepatocellular carcinoma. 

PMID- 24132681
TI  - Prosthesis-patient mismatch in aortic stenosis.
AB  - BACKGROUND: The clinical impacts of prosthesis-patient mismatch (PPM) after
      aortic valve replacement (AVR) have been debated since Rahimtoola first reported
      PPM in 1978. Many reports discussing several aspects of PPM have been published
      to date, but the definitive clinical impacts of PPM have not yet been clarified.
      PURPOSE: The purpose of this review is to evaluate recent articles regarding PPM
      and discuss the latest findings. RESULTS: Moderate PPM (indexed effective orifice
      area <= 0.85 cm(2)/m(2)) did not affect the surgical outcomes in several papers,
      but severe PPM (indexed effective orifice area <= 0.65 cm(2)/m(2)) affected early
      and late mortality in almost of the all papers in which it was reported. PPM had
      a greater effect on younger patients and patients with left ventricular
      dysfunction than it did on elderly patients and patients with preserved left
      ventricular function. CONCLUSION: Based on recent findings, it is difficult to
      define the impact of PPM after AVR. To some degree, PPM affects the clinical
      outcomes after AVR; therefore, it is important to avoid PPM, especially severe
      PPM.

PMID- 24132682
TI  - Clinical applications of capillary electrophoresis based immunoassays.
AB  - Immunoassays have long been an important set of tools in clinical laboratories
      for the detection, diagnosis, and treatment of disease. Over the last two
      decades, there has been growing interest in utilizing CE as a means for
      conducting immunoassays with clinical samples. The resulting method is known as a
      CE immunoassay. This approach makes use of the selective and strong binding of
      antibodies for their targets, as is employed in a traditional immunoassay, and
      combines this with the speed, efficiency, and small sample requirements of CE.
      This review discusses the variety of ways in which CE immunoassays have been
      employed with clinical samples. An overview of the formats and detection modes
      that have been employed in these applications is first presented. A more detailed
      discussion is then given on the type of clinical targets and samples that have
      been measured or studied by using CE immunoassays. Particular attention is given
      to the use of this method in the fields of endocrinology, pharmaceutical
      measurements, protein and peptide analysis, immunology, infectious disease
      detection, and oncology. Representative applications in each of these areas are
      described, with these examples involving work with both traditional and
      microanalytical CE systems.

PMID- 24132683
TI  - Spontaneous hemopneumothorax: epidemiological details and clinical features.
AB  - PURPOSES: Spontaneous hemopneumothorax (SHP) may cause life-threatening blood
      loss. The objective of this study was to elucidate the epidemiological and
      clinical features of SHP. METHODS: We reviewed the records of 26 patients who
      underwent surgery for SHP between 1989 and 2010. We evaluated their epidemiology
      and clinical features by comparing them with those of 681 patients with
      spontaneous pneumothorax treated during the same period. RESULTS: The proportion
      of smokers in the SHP group was higher than that in the spontaneous pneumothorax
      group (P < 0.01). Seventeen cases (65.4 %) of SHP occurred on the left side. The
      most frequent bleeding area was the superior thoracic aperture (STA:17 cases,
      65.4 %), followed by the left superior mediastinum (six cases, 23.1 %). Ten cases
      had intrathoracic clots greater than 500 mL, which could not be drained
      preoperatively. The postoperative stay of patients treated with video-assisted
      thoracic surgery (VATS) was shorter than that of patients treated with open
      thoracotomy (21 versus five cases; P < 0.05). CONCLUSIONS: A higher proportion of
      smokers was revealed in the SHP patients. VATS shortened the hospital stay of the
      patients. The particular areas that should be observed intraoperatively are the
      STA and the left superior mediastinum.

PMID- 24132684
TI  - Thyroidectomy in a patient with thyroid storm: report of a case.
AB  - Thyroid storm is a life-threatening condition that is generally considered to be
      a contradiction to surgical intervention. We herein describe the case of a 37
      year-old patient with a history of Graves' disease who was transferred to Tottori
      University Hospital with thyroid storm. She had been followed by her family
      doctor since 2006, but she had stopped taking her medication of her own volition
      in 2010. About ten days prior to her admission at our hospital, she consulted her
      family doctor with complaints of dyspnea, palpitations and general fatigue.
      Subsequent thyroid function tests showed TSH < 0.01 MUU/ml, FT3 25.0 pg/ml and
      FT4 8.0 ng/dl. She also had acute heart failure, atrial fibrillation and hepatic
      failure. A diagnosis of thyroid storm was made and she was transferred to our
      hospital. She received steroids, beta blockade, potassium iodide, and plasma
      exchange, but her hepatic failure did not resolve and her clinical condition
      deteriorated. The decision was made to proceed with thyroidectomy.
      Postoperatively, her hepatic function normalized. Thus, thyroidectomy is a
      potential therapeutic choice for cases of thyroid storm refractory to medical
      management.

PMID- 24132685
TI  - A simple prediction rule for all-cause mortality in a cohort eligible for
      bariatric surgery.
AB  - IMPORTANCE: Current eligibility criteria for bariatric surgery use arbitrarily
      chosen body mass index (BMI) (calculated as weight in kilograms divided by height
      in meters squared) thresholds, an approach that has been criticized as arbitrary
      and lacking evidence. OBJECTIVES: To verify the importance of BMI as a mortality
      predictor, to identify other important mortality predictors, and to construct a
      mortality prediction rule in a population eligible for bariatric surgery. DESIGN:
      We studied individuals from a population-representative register who met
      contemporary eligibility criteria for bariatric surgery (BMI, >=35.0 alone or
      30.0-34.9 with an obesity-related comorbidity) from January 1, 1988, through
      December 31, 1998. We used binary logistic regression to construct a parsimonious
      model and a clinical prediction rule for 10-year all-cause mortality. SETTING:
      The United Kingdom General Practice Research Database, a population
      representative primary care registry. PARTICIPANTS: Fifteen thousand three
      hundred ninety-four patients aged 18 to 65 years. EXPOSURE: Bariatric surgery.
      MAIN OUTCOME AND MEASURE: Ten-year all-cause mortality. RESULTS: Mean (SD) age
      was 46.9 (11.9) years, BMI was 36.2 (5.5), and 63.2% of the patients were women.
      All-cause mortality was 2.1%, and mean follow-up duration was 9.9 years. The
      final model, which included age (odds ratio, 1.09 per year [95% CI, 1.07-1.10]),
      type 2 diabetes mellitus (2.25 [1.76-2.87]), current smoking (1.62 [1.28-2.06]),
      and male sex (1.50 [1.20-1.87]), had a C statistic of 0.768. Although BMI
      significantly predicted mortality (odds ratio, 1.03 per unit [95% CI, 1.01
      1.05]), it did not improve model discrimination or calibration. We divided
      clinical prediction rule scoring into 4 tiers. All-cause mortality was 0.2% in
      tier 1, 0.9% in tier 2, 2.0% in tier 3, and 5.2% in tier 4. CONCLUSIONS AND
      RELEVANCE: All-cause 10-year mortality in obese individuals eligible for
      bariatric surgery can be estimated using a simple 4-variable prediction rule
      based on age, sex, smoking, and diabetes mellitus. Body mass index was not an
      important mortality predictor. Further work is needed to define low, moderate,
      and high absolute risk thresholds and to provide external validation.

PMID- 24132687
TI  - High ambient temperatures and hypokalaemia.

PMID- 24132686
TI  - Combining computational methods for hit to lead optimization in Mycobacterium
      tuberculosis drug discovery.
AB  - PURPOSE: Tuberculosis treatments need to be shorter and overcome drug resistance.
      Our previous large scale phenotypic high-throughput screening against
      Mycobacterium tuberculosis (Mtb) has identified 737 active compounds and
      thousands that are inactive. We have used this data for building computational
      models as an approach to minimize the number of compounds tested. METHODS: A
      cheminformatics clustering approach followed by Bayesian machine learning models
      (based on publicly available Mtb screening data) was used to illustrate that
      application of these models for screening set selections can enrich the hit rate.
      RESULTS: In order to explore chemical diversity around active cluster scaffolds
      of the dose-response hits obtained from our previous Mtb screens a set of 1924
      commercially available molecules have been selected and evaluated for
      antitubercular activity and cytotoxicity using Vero, THP-1 and HepG2 cell lines
      with 4.3%, 4.2% and 2.7% hit rates, respectively. We demonstrate that models
      incorporating antitubercular and cytotoxicity data in Vero cells can
      significantly enrich the selection of non-toxic actives compared to random
      selection. Across all cell lines, the Molecular Libraries Small Molecule
      Repository (MLSMR) and cytotoxicity model identified ~10% of the hits in the top
      1% screened (>10 fold enrichment). We also showed that seven out of nine Mtb
      active compounds from different academic published studies and eight out of
      eleven Mtb active compounds from a pharmaceutical screen (GSK) would have been
      identified by these Bayesian models. CONCLUSION: Combining clustering and
      Bayesian models represents a useful strategy for compound prioritization and hit
      to lead optimization of antitubercular agents.

PMID- 24132688
TI  - Acute fourth nerve paresis.

PMID- 24132689
TI  - Management of recurrent chalazia.

PMID- 24132690
TI  - Urgent ophthalmic examination for renal tubular acidosis. Infantile nephropathic
      cystinosis.

PMID- 24132691
TI  - A video educational and consenting system for ROP.

PMID- 24132692
TI  - Unilateral myelinated nerve fibers associated with ipsilateral myopia and
      amblyopia.

PMID- 24132693
TI  - Hyaline fibromatosis of Hoffa's fat pad in a patient with a mild type of hyaline
      fibromatosis syndrome.
AB  - Hyaline fibromatosis syndrome (HFS) is a rare, homozygous, autosomal recessive
      disease, characterized by deposition of hyaline material in skin and other
      organs, resulting in esthetic problems, disability, and potential life
      threatening complications. Most patients become clinically apparent in the first
      few years of life, and the disorder typically progresses with the appearance of
      new lesions. We describe a rare case of a 20-year-old patient with juvenile-onset
      mild HFS who presented with a history of progressive anterior knee pain. Detailed
      magnetic resonance (MR) imaging findings with histopathological correlation are
      presented of hyaline fibromatosis of Hoffa's fat pad, including differential
      diagnosis. The diagnosis of HFS is generally made on basis of clinical and
      histopathological findings. Imaging findings, however, may contribute to the
      correct diagnosis in patients who present with a less typical clinical course of
      HFS. 

PMID- 24132694
TI  - Familial history of non-medullary thyroid cancer is an independent prognostic
      factor for tumor recurrence in younger patients with conventional papillary
      thyroid carcinoma.
AB  - BACKGROUND: It is not clear whether familial non-medullary thyroid cancer (FNMTC)
      is more aggressive and has a poorer prognosis, than sporadic carcinoma.
      Therefore, the optimal clinical approach for FNMTC is yet to be established. In
      this study, we investigated the biological behavior and prognosis of FNMTC
      compared with its sporadic counterpart. METHODS: Between 1996 and 2004, 1,262
      patients underwent a total thyroidectomy for conventional PTC at Asan Medical
      Center and 113 (9.0%) were diagnosed with FNMTC. We compared the clinico
      pathologic characteristics, treatment modalities, and prognosis between familial
      and sporadic NMTC. RESULTS: FNMTC was significantly more multi-centric than
      sporadic. We also found that family history itself was an independent risk factor
      for recurrence. Moreover, disease-free survival in the familial group was
      significantly shorter than in the sporadic group in the subgroups in which age
      was <45 years, and in which the tumors were multi-centric, bilateral, and of N1b
      node status. CONCLUSION: FNMTC may be considered as a separate clinical entity
      with a higher rate of recurrence and worse DFS than its sporadic counterpart.
      Furthermore, familial history of NMTC is an independent risk factor for
      recurrence, especially in younger patients with conventional PTC.

PMID- 24132695
TI  - Ab initio study on the noncovalent adsorption of camptothecin anticancer drug
      onto graphene, defect modified graphene and graphene oxide.
AB  - The application of graphene and related nanomaterials like boron nitride (BN)
      nanosheets, BN-graphene hybrid nanomaterials, and graphene oxide (GO) for
      adsorption of anticancer chemotherapeutic camptothecin (CPT) along with the
      effect on electronic properties prior to functionalization and after
      functionalization has been reported using density functional theory (DFT)
      calculations. The inclusion of dispersion correction to DFT is instrumental in
      accounting for van der Waals pi-pi stacking between CPT and the nanomaterial. The
      adsorption of CPT exhibits significant strain within the nanosheets and
      noncovalent adsorption of CPT is thermodynamically favoured onto the nanosheets.
      In case of GO, surface incorporation of functional groups result in significant
      crumpling along the basal plane and the interaction is basically mediated by H
      bonding rather than pi-pi stacking. Docking studies predict the plausible binding
      of CPT, CPT functionalized graphene and GO with topoisomerase I (top 1)
      signifying that CPT interacts through pi stacking with AT and GC base pairs of
      DNA and in presence of nano support, DNA bases preferentially gets bound to the
      basal plane of graphene and GO rather than the edges. At a theoretical level of
      understanding, our studies point out the noncovalent interaction of CPT with
      graphene based nanomaterials and GO for loading and delivery of anticancer
      chemotherapeutic along with active binding to Top1 protein. 

PMID- 24132696
TI  - Serial sub-conjunctival 5-Fluorouracil for early recurrent anophthalmic
      contracted socket.
AB  - BACKGROUND: To evaluate the effects and side-effects of serial sub-conjunctival
      injections of 5-fluorouracil (5-FU) in early postoperative period for recurrent
      anophthalmic contracted socket. METHODS: Retrospective comparative case series at
      tertiary eye care centre including fifteen adult patients with features of
      postoperative recurrent socket contraction after buccal mucosal graft. Group A
      comprised eight patients treated with 10 mg weekly sub-conjunctival injection of
      5-FU in the fornices. Group B comprised seven patients taken as control. Main
      outcome measures were: superior fornix depth (SFD), inferior fornix depth (IFD),
      and socket volume (SV) at 6 months follow up. Patients were re-evaluated
      clinically for recurrence at last follow-up. RESULTS: The mean +/- SD values in
      group A versus group B were as follows: 10 +/- 1.6 mm vs 5.1 +/- 0.9 mm (p <
      0.005) for SFD, 6.7 +/- 1.5 mm vs 3.5 +/- 0.5 mm (p = 0.02) for IFD; and 2 +/-
      0.55 ml versus 0.27 +/- 0.06 ml (p = 0.005) for SV at 6 months. There was
      significant improvement in depth of fornices and volume of socket in seven
      patients in group A. One patient in group A did not benefit from 5-FU treatment.
      The beneficial effects of 5-FU were observed when first injection was given
      within 4 weeks after socket reconstruction. There was no recurrence (in six
      cases) and no side-effects seen in group A at final follow-up of 18.2 (12-24)
      months. CONCLUSIONS: Weekly injections of 5-FU are effective for stopping the
      progression of recurrent contracted socket following primary reconstructive
      surgery. It provides early rehabilitation, and avoids repetitive surgery.

PMID- 24132697
TI  - Determination of different forms of aminothiols in red blood cells without
      washing erythrocytes.
AB  - Detection and quantification of different aminothiols forms (reduced and total)
      in biological fluids are important for the investigation of oxidative stress
      related diseases and cell homeostasis study. The aim of this study was to
      optimize a HPLC method in order to determine both reduced and total thiol forms
      in red blood cells (RBC) at low temperature without washing erythrocytes.
      Analytical recoveries for total and reduced thiols were 91.6-98.5 and 94.9-98.2%
      respectively. The relative standard deviations intra-assay for total and reduced
      thiols were 1.14-3.64 and 0.83-2.3% respectively and the relative standard
      deviations inter-assay for total and reduced thiols were 1.12-3.54 and 0.84
      2.03%, respectively. This method allows specific analysis of the aminothiol state
      inside the RBC, as a model of intracellular metabolism functioning.

PMID- 24132699
TI  - Repetitive transcranial magnetic stimulation transiently reduces punding in
      Parkinson's disease: a preliminary study.
AB  - Amongst the impulse-control disorders (ICDs) associated with dopamine-replacement
      therapy in patients with Parkinson's disease (PD) is a repetitive, complex,
      stereotyped behaviour called punding. Disruption of the reciprocal loops between
      the striatum and structures in the prefrontal cortex (PFC) following dopamine
      depletion may predispose patients with PD to these behavioural disorders. The
      purpose of the present study was to assess the effects of repetitive transcranial
      magnetic stimulation (rTMS) over the dorsolateral PFC (DLPFC) on punding in PD.
      We used low-frequency (LF) rTMS in four PD patients presenting with punding.
      Punding was transiently reversed by LF-rTMS over the DLPFC without enhancing
      motor impairment. The effect was more sustained after right DLPFC rTMS.
      Therefore, LF-rTMS produced a transient beneficial effect in PD patients with
      punding, similar to that reported in PD patients with levodopa-induced
      dyskinesias. rTMS might have therapeutic potential for the treatment of punding
      and perhaps other ICDs in PD. 

PMID- 24132698
TI  - Dexamethasone in the presence of desipramine enhances MAPK/ERK1/2 signaling
      possibly via its interference with beta-arrestin.
AB  - Antidepressant medication is the standard treatment for major depression disorder
      (MDD). However, the response to these treatments is often incomplete and many
      patients remain refractory. In the present study, we show that the glucocorticoid
      receptor (GR) agonist dexamethasone (DEX) increased MAPK/ERK1/2 signaling in the
      presence of the noradrenergic antidepressant, desipramine (DMI), while no such
      effect was induced by DEX or DMI alone in human neuroblastoma SH-SY5Y cells. This
      enhancement was dependent on the activation of both alpha(2) adrenergic receptors
      (AR) and GR. The timing of MAPK/ERK1/2 activation as well as DEX-induced
      reduction in membranous alpha(2) AR suggests the involvement of a beta-arrestin
      dependent mechanism. In line with the latter, DEX increased cytosolic and
      decreased membranous levels of beta-arrestin. Concomitantly, DEX induced a time
      dependent increase in cytosolic alpha(2) AR-beta-arrestin interaction and a
      decrease in beta-arrestin interaction with Mdm2 E3 ubiquitin ligase. All of these
      effects of DEX were prevented by the GR antagonist RU486. Our data suggest an
      additional intracellular role for DEX, in which activation of GR interferes with
      the trafficking and degradation of beta-arrestin-alpha2c-AR complex. We suggest
      that such an interaction in the presence of DMI can enhance MAPK/ERK1/2
      signaling, a key player in neural plasticity and neurogenesis processes, which is
      impaired in MDD, while stimulated by antidepressants.

PMID- 24132700
TI  - Factors affecting particle collection by electro-osmosis in microfluidic systems.
AB  - Alternating-current electro-osmosis, a phenomenon of fluid transport due to the
      interaction between an electrical double layer and a tangential electric field,
      has been used both for inducing fluid movement and for the concentration of
      particles suspended in the fluid. This offers many advantages over other
      phenomena used to trap particles, such as placing particles at an electrode
      centre rather than an edge; benefits of scale, where electrodes hundreds of
      micrometers across can trap particles from the molecules to cells at the same
      rate; and a trapping volume limited by the vortex height, a phenomenon thus far
      unstudied. In this paper, the collection of particles due to alternating-current
      electro-osmosis driven collection is examined for a range of particle
      concentrations, inter-electrode gap widths, chamber heights and media viscosity
      and density. A model of collection behaviour is described where particle
      collection over time is governed by two processes, one driven by the vortices and
      the other by sedimentation, allowing the determination of the maximum height of
      vortex-driven collection, but also indicates how trapping is limited by high
      particle concentrations and fluid velocities. The results also indicate that
      viscosity, rather than density, is a significant governing factor in determining
      the trapping behaviour of particles. 

PMID- 24132701
TI  - Comparative effect of antihypertensive therapy on blood glucose level in
      hypertensive patients in an Indian population.
AB  - Hypertensive patients have higher prevalence of insulin resistance and are at
      increased risk of developing type 2 diabetes mellitus (DM). There is scarcity of
      data on the relationship between antihypertensive therapies and glycaemic control
      in Indian population. Thus, the present study was designed to investigate such
      association among Indian population in a University teaching hospital.The study
      was carried out on 177 hypertensive patients (with new onset of diabetes or
      without diabetes) visiting the OPD of medicine department at Majeedia hospital,
      New Delhi. The drug history of hypertensive patients and blood glucose levels
      following 1-5 yrs of antihypertensive therapy were recorded.The gender
      distribution of hypertensive patients reveals a higher percentage of incidences
      in males (53.7%) as compared to females (46.3%). Hypertensive patient without DM
      on beta blockers and on thiazide shows higher incidence of impaired glucose
      tolerance (IGT) (17.5%, 18.5%) and DM (10%, 11%) as compared to patient receiving
      other antihypertensive therapy. While in patients of new onset diabetes the
      incidence was higher with beta-blockers (56.2%) than with thiazides (31.3%)
      followed by calcium channel blockers (CCBs) (12.5%). There was proportionate
      increase in incidence with the duration of therapy (3-5 years). None of the
      patients who were on ACE inhibitors or on angiotensin receptor blockers (ARBs)
      reported any incidence of IGT or DM.To conclude, beta-blockers and thiazides
      increases the risk of type 2 diabetes mellitus with long term antihypertensive
      therapy requiring regular monitoring. CCBs have lowered risks while ACE
      inhibitors and ARBs are relatively free of such metabolic adverse effects. 

PMID- 24132702
TI  - Gradient HPLC-DAD determination of paracetamol, phenylephrine hydrochloride,
      cetirizine in tablet formulation.
AB  - Present work describes the development and validation of a simple and reliable
      high-performance liquid chromatography-diode array detection (HPLC-DAD) procedure
      for the analysis of phenylephrine hydrochloride (PHE), paracetamol (PAR) and
      cetirizine dihydrochloride (CET), in pharmaceutical mixture. The method was
      applied successfully on tablet dosage form. Effective chromatographic separation
      of PHE, PAR and CET was achieved using a Kinetex-C18 (4.6, 150 mm, 5 mm) column
      with gradient elution of the mobile phase composed of 10 mM phosphate buffer (pH
      3.3) and acetonitrile. The elution was a 3 step gradient elution program step-1
      started initially with 2% (by volume) acetonitrile and 98% phosphate buffer (pH
      3.3) for first 2 min. In step-2 acetonitrile concentration changed linearly to
      20% upto 12 min the analysis was concluded by step-3 changing acetonitrile to 2%
      upto 20 min. The reliability and analytical performance of the proposed HPLC
      procedure were statistically validated with respect to linearity, ranges,
      precision, accuracy, selectivity and robustness. Calibration curves were linear
      in the ranges 5-15, 250-750 and 2.5-7.5 MUg/ml for PHE, PAR and CET, with
      correlation coefficients >0.9996. The validated HPLC method was applied to a
      pharmaceutical mixture of a marketed preparation tablet in which the analytes
      were successfully quantified with good recovery values with no interfering peaks
      from the excipents. 

PMID- 24132703
TI  - Evaluation of wound healing property of Terminalia catappa on excision wound
      models in Wistar rats.
AB  - Wound is defined as the loss of breaking cellular and functional continuity of
      the living tissues. Management of wounds is frequently encountered with different
      problems. Drug resistance and toxicity hindered the development of synthetic
      antimicrobial agents with wound healing activity. Many plants with potent
      pharmacological activities may offer better treatment options viz. Terminalia
      chebula, Terminalia bellirica and Phyllanthus emblica formulations have shown
      healing activities on wounds.The present study was planned to investigate the
      wound healing activity of Terminalia catappa on excision wound model in rats.
      Ointment was prepared by using bark extract of Terminalia catappa in soft
      paraffin and preservative. Wistar albino rats (200-250 gm) of either sex were
      used in the present study. A circular wound of 2 cm in diameter was made on the
      depilated dorsal thoracic region of the rats under ether anesthesia in aseptic
      conditions. The ointment was applied for 18 days and percent wound closure
      observed along with the parameters viz. Epithelization, granuloma weight and scar
      formation. Animals were observed on 3rd, 6th, 9th, 12th, 15th and 18th post
      wounding day.Wound healing activity was compared with that of control and
      Betadine ointment as standard drug. Animals treated with Terminalia catappa
      ointment exhibited 97% reduction in wound area as compared to the control animals
      (81%). Ointment treated wounds were found to induce epithelization faster
      compared to the control. In conclusion, Terminalia catappa ointment promotes
      significant wound healing in rats and further evaluation of this activity in
      humans is suggested. 

PMID- 24132704
TI  - Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1/2
      pathway in rat liver.
AB  - INTRODUCTION: Diazinon Yis one of the most broadly used organophosphorus
      insecticides in agriculture. It has been shown that exposure to diazinon may
      interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has
      been established. Earlier studies revealed the major role of Extracellular signal
      regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr)
      expression. The aim of this study was to evaluate changes in the regulation of
      lipid metabolism, ERK and LDLr expression in the liver of rats exposed to
      subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced
      disturbed cholesterol homeostasis was studied. METHODS: 24 Rats were divided into
      4 groups and received following treatments for 4 weeks; Corn oil (control),
      diazinon (15mg/kg per day, orally) and crocin (12.5 and 25mg/kg per day,
      intraperitoneally) in combination with diazinon (15 mg/kg). The levels of
      cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA
      levels of LDLr and ERK1/2 as well as protein levels of total and activated forms
      of ERK1/2 in rat liver were evaluated by Western blotting and quantitative real
      time polymerase chain reaction analysis. RESULTS: Our data showed that subacute
      exposure to diazinon significantly increased concentrations of cholesterol,
      triglyceride and LDL. Moreover diazinon decreased ERK1/2 protein phosphorylation
      and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon
      induced hyperlipemia and increased levels of LDLr transcript. CONCLUSIONS: Crocin
      may be considered as a novel protective agent in diazinon-induced hyperlipemia
      through modulating of ERK pathway and increase of LDLr expression.

PMID- 24132705
TI  - The influence of food on the pharmacokinetics of amlodipine and losartan after
      single-dose of its compound tablets in healthy chinese subjects.
AB  - We aim to identify the effects of food on the pharmacokinetics (PK) of
      amlodipine, losartan and losartan's active metabolite (EXP3174) after oral
      administration of the Compound Amlodipine Tablets with single dose in healthy
      Chinese subjects. 12 subjects took the compounds (10 mg/100 mg,
      amlodipine/losartan) at the conditions of a high-fat breakfast and an overnight
      fast with a washout period of 14 days. Plasma samples were obtained at scheduled
      time, and determined by HPLC-MS/MS for the concentrations of amlodipine and HPLC
      MS for the concentrations of losartan and EXP3174, respectively. PK parameters
      were calculated using Software Drug and Statistics (Version 2.0). When tablets
      were co-administered with food, there was no significant difference of AUC for
      amlodipine and losartan, but the AUC of EXP3174 was reduced by 19.1%. Meanwhile,
      the Cmax of amlodipine, losartan and EXP3174 were reduced by 11.4%, 20.0% and
      41.4%, and the Tmax of losartan and EXP3174 were 1.3 and 1.8 h longer,
      respectively. No significant difference was found at t1/2 following food intake.
      In conclusion, the Compound Amlodipine Tablets, are affected by food
      administration by reducing the AUC of EXP3174. It is thus suggested that the
      Compound Amlodipine Tablets should be administered 1 h before or 2 h after meal. 

PMID- 24132706
TI  - To investigate antihyperglycemic and antihyperlipidemic potential of safrole in
      rodents by in-vivo and in-vitro study.
AB  - In the present investigation anti-diabetic and in-vitro antioxidant potential of
      safrole were evaluated (100 and 200 mg/kg p.o.) in acute and chronic
      Streptozotocin-nicotinamide (STZ) induced antihyperglycemic rat model. The oral
      administration of safrole for 30 days affects the level of blood glucose,
      glycosylated hemoglobin (HbA1C), total cholesterol (TC), triglycerides (TG),
      phospholipids, high density lipoprotein (HDL), body weight, insulin level, liver
      glycogen content, antioxidant parameters, lipase, alpha-amylase in normal and STZ
      induced diabetic rats. The oral administration of safrole at dose 100 & 200 mg/kg
      p.o. significantly improve the diabetic condition in Streptozotocin-induced
      diabetic rats. In enzymatic assay, the IC50 value of the safrole for alpha
      amylase and lipase was found to be 702.78 and 861.35 MUg/ml respectively which
      was found comparable with the standard drug (ascorbic acid) as 252.12 MUg/ml.
      Further studies can be performed on safrole for mechanistic and toxicological
      aspects so that it can be investigated as a new substance for the management of
      various diseases. 

PMID- 24132707
TI  - Bioequivalence study of 8 mg ondansetron film-coated tablets in healthy Caucasian
      volunteers.
AB  - The aim of the study was to investigate the bioequivalence of a generic product
      of 8 mg film-coated tablets (test) to the branded product (reference) at the same
      strength in order to apply for regulatory approval. The secondary objective of
      the study was to compare the tolerability of both products. A double blinded,
      randomized, cross-over, 2-period, comparative study was conducted in healthy
      Caucasian volunteers under fasting conditions. A single oral dose administration
      of the test or reference product was followed by a 7-day wash-out period. The
      ondansetron concentration was determined using a validated high performance
      liquid chromatography with a UV detection method. The 90% confidence interval of
      the point estimate (test over reference products) for C(max) and AUC(0-t) fell
      within the 80.00-125.00% acceptance range. The results of the study indicate that
      the film-coated tablets of Ondatron 8 mg manufactured by Tarchominskie Zaklady
      Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zofran
      manufactured by GlaxoSmithKline Export Ltd (reference product). Both products
      were well tolerated.

PMID- 24132708
TI  - Composite measures for profiling hospitals on bariatric surgery performance.
AB  - IMPORTANCE: The optimal approach for profiling hospital performance with
      bariatric surgery is unclear. OBJECTIVE: To develop a novel composite measure for
      profiling hospital performance with bariatric surgery. DESIGN, SETTING, AND
      PARTICIPANTS: Using clinical registry data from the Michigan Bariatric Surgery
      Collaborative, we studied all patients undergoing bariatric surgery from January
      1, 2008, through December 31, 2010. For laparoscopic gastric bypass surgery, we
      used empirical Bayes techniques to create a composite measure by combining
      several measures, including serious complications, reoperations, and
      readmissions; hospital and surgeon volume; and outcomes with other related
      procedures. Hospitals were ranked for 2008 through 2009 and placed in 1 of 3
      groups: 3-star (top 20%), 2-star (middle 60%), and 1-star (bottom 20%). We
      assessed how well these ratings predicted outcomes in the next year (2010)
      compared with other widely used measures. MAIN OUTCOMES AND MEASURES: Risk
      adjusted serious complications. RESULTS: Composite measures explained a larger
      proportion of hospital-level variation in serious complication rates with
      laparoscopic gastric bypass than other measures. For example, the composite
      measure explained 89% of the variation compared with only 28% for risk-adjusted
      complication rates alone. Composite measures also appeared better at predicting
      future performance compared with individual measures. When ranked on the
      composite measure, 1-star hospitals had 2-fold higher serious complication rates
      (4.6% vs 2.4%; odds ratio, 2.0; 95% CI, 1.1-3.5) compared with 3-star hospitals.
      Differences in serious complication rates between 1- and 3-star hospitals were
      much smaller when hospitals were ranked using serious complications (4.0% vs
      2.7%; odds ratio, 1.6; 95% CI, 0.8-2.9) and hospital volume (3.3% vs 3.2%; odds
      ratio, 0.85; 95% CI, 0.4-1.7). CONCLUSIONS AND RELEVANCE: Composite measures are
      much better at explaining hospital-level variation in serious complications and
      predicting future performance than other approaches. In this preliminary study,
      it appears that such composite measures may be better than existing alternatives
      for profiling hospital performance with bariatric surgery.

PMID- 24132709
TI  - Interference of spoken word recognition through phonological priming from visual
      objects and printed words.
AB  - Three cross-modal priming experiments examined the influence of preexposure to
      pictures and printed words on the speed of spoken word recognition. Targets for
      auditory lexical decision were spoken Dutch words and nonwords, presented in
      isolation (Experiments 1 and 2) or after a short phrase (Experiment 3). Auditory
      stimuli were preceded by primes, which were pictures (Experiments 1 and 3) or
      those pictures' printed names (Experiment 2). Prime-target pairs were
      phonologically onset related (e.g., pijl-pijn, arrow-pain), were from the same
      semantic category (e.g., pijl-zwaard, arrow-sword), or were unrelated on both
      dimensions. Phonological interference and semantic facilitation were observed in
      all experiments. Priming magnitude was similar for pictures and printed words and
      did not vary with picture viewing time or number of pictures in the display
      (either one or four). These effects arose even though participants were not
      explicitly instructed to name the pictures and where strategic naming would
      interfere with lexical decision making. This suggests that, by default,
      processing of related pictures and printed words influences how quickly we
      recognize spoken words. 

PMID- 24132710
TI  - Using scissors to bisect a line: a perception-action dissociation in complex tool
      use.
AB  - Previous research has shown that unilateral visual neglect is improved when
      patients are required to actively grasp an object at its center, rather than only
      pointing to its center. A similar dissociation between pointing and grasping
      responses has been reported for pseudoneglect, a spatial bias toward the left
      side of space that is normally exhibited by healthy participants. Among other
      theories, the two-visual-streams hypothesis has been offered as an explanation
      for these dissociations. According to this hypothesis, highly practiced actions
      that are performed under easily available visual input (e.g., grasping an object)
      are controlled by the dorsal stream and can resist perceptual judgment biases. We
      investigated whether, in pseudoneglect, dissociations between perceptual
      judgments and motor-manipulative responses occur when participants have to
      respond with complex tools that are highly practiced but that have been shown to
      rely on both ventral- and dorsal-stream processing. In a standard line bisection
      task, participants had to either mark the center of a line with a pencil or cut
      the line in two halves using a pair of scissors. The results indicated the
      typical leftward bias (pseudoneglect) in the pencil task, whereas performance was
      much more accurate in the scissors task. These results show that actions
      featuring complex tool use can resist perceptual judgment biases, and the
      findings are discussed with reference to existing accounts of perception-action
      dissociations. 

PMID- 24132711
TI  - Responding to the direction of the eyes: in search of the masked gaze-cueing
      effect.
AB  - Recent studies have demonstrated that masked gaze cues can produce a cueing
      effect. Those studies, however, all utilized a localization task and, hence, are
      ambiguous with respect to whether the previously observed masked gaze-cueing
      effect reflects the orienting of attention or the preparation of a motor
      response. The aim of the present study was to investigate this issue by
      determining whether masked gaze cues can modulate responses in detection and
      discrimination tasks, both of which isolate spatial attention from response
      priming. First, we found a gaze-cueing effect for unmasked cues in detection,
      discrimination, and localization tasks, which suggests that the gaze-cueing
      effect for visible cues is not task dependent. Second, and in contrast, we found
      a gaze-cueing effect for masked cues in a localization task, but not in detection
      or discrimination tasks, which suggests that the gaze-cueing effect for masked
      cues is task dependent. Therefore, the present study shows that the masked gaze
      cueing effect is attributed to response priming, as opposed to the orienting of
      spatial attention. 

PMID- 24132712
TI  - Seasonal changes in burrow geometry of the common mole rat (Rodentia:
      Bathyergidae).
AB  - Sociality in mole rats has been suggested to have evolved as a response to the
      widely dispersed food resources and the limited burrowing opportunities that
      result from sporadic rainfall events. In the most arid regions, individual
      foraging efficiency is reduced, and energetic constraints increase. In this
      study, we investigate seasonal differences in burrow architecture of the social
      Cryptomys hottentotus hottentotus in a mesic region. We describe burrow geometry
      in response to seasonal weather conditions for two seasons (wet and dry).
      Interactions occurred between seasons and colony size for the size of the burrow
      systems, but not the shape of the burrow systems. The fractal dimension values of
      the burrow systems did not differ between seasons. Thus, the burrow complexity
      was dependent upon the number of mole rats present in the social group. 

PMID- 24132713
TI  - An analysis of natural mentoring relationship profiles and associations with
      mentees' mental health: considering links via support from important others.
AB  - We explored associations between natural mentoring relationship profiles and
      young adults' life satisfaction and symptoms of depression via participants'
      perceived support from important others accounting for participants' perceived
      support and mental health prior to the onset of their natural mentoring
      relationships. Participants included 396 young adults (57% female; mean age =
      30.97, SD = .6), the majority of whom identified as Black or African American
      (79% Black, 18% White, 3% Biracial). Most participants had completed high school
      but few participants (13%) had completed degrees from 4 year institutions. We
      used a latent profile approach to identify natural mentoring relationship
      profiles and employed structural equation modeling to test our study hypotheses.
      Slightly over half of study participants (53%) reported the presence of a natural
      mentor in their lives since the age of 14. Results suggest that natural mentoring
      relationships characterized by high levels of relational closeness and either
      extended relationship duration or frequent contact may promote improvements in
      psychological well-being among mentees over time via greater experiences of
      social support from important others.

PMID- 24132714
TI  - Poorer right ventricular systolic function and exercise capacity in women after
      repair of tetralogy of fallot: a sex comparison of standard deviation scores
      based on sex-specific reference values in healthy control subjects.
AB  - BACKGROUND: In repaired congenital heart disease, there is increasing evidence of
      sex differences in cardiac remodeling, but there is a lack of comparable data for
      specific congenital heart defects such as in repaired tetralogy of Fallot.
      METHODS AND RESULTS: In a prospective multicenter study, a cohort of 272
      contemporary patients (158 men; mean age, 14.3+/-3.3 years [range, 8-20 years])
      with repaired tetralogy of Fallot underwent cardiac magnetic resonance for
      ventricular function and metabolic exercise testing. All data were transformed to
      standard deviation scores according to the Lambda-Mu-Sigma method by relating
      individual values to their respective 50th percentile (standard deviation score,
      0) in sex-specific healthy control subjects. No sex differences were observed in
      age at repair, type of repair conducted, or overall hemodynamic results. Relative
      to sex-specific controls, repaired tetralogy of Fallot in women had larger right
      ventricular end-systolic volumes (standard deviation scores: women, 4.35; men,
      3.25; P=0.001), lower right ventricular ejection fraction (women, -2.83; men, 
      2.12; P=0.011), lower right ventricular muscle mass (women, 1.58; men 2.45;
      P=0.001), poorer peak oxygen uptake (women, -1.65; men, -1.14; P<0.001), higher
      VE/VCO2 (ventilation per unit of carbon dioxide production) slopes (women, 0.88;
      men 0.58; P=0.012), and reduced peak heart rate (women, -2.16; men -1.74;
      P=0.017). Left ventricular parameters did not differ between sexes. CONCLUSIONS:
      Relative to their respective sex-specific healthy control subjects, derived
      standard deviation scores in repaired tetralogy of Fallot suggest that women
      perform poorer than men in terms of right ventricular systolic function as tested
      by cardiac magnetic resonance and exercise capacity. This effect cannot be
      explained by selection bias. Further outcome data are required from longitudinal
      cohort studies.

PMID- 24132715
TI  - Antenatal screening for Down Syndrome and other chromosomal abnormalities:
      increasingly complex issues.

PMID- 24132716
TI  - A comparison of different mask holds for positive pressure ventilation in a
      neonatal manikin.
AB  - BACKGROUND: Ventilation during neonatal resuscitation is typically initiated with
      a face mask, but may be ineffective due to leak or obstruction. OBJECTIVE: To
      compare leak using three methods of mask hold. METHODS: Medical and nursing staff
      regularly involved in neonatal resuscitation used the three holds (two-point, two
      handed, spider) on a manikin in a random order to apply positive pressure
      ventilation (PPV) at standard settings each for 1 min while mask leak was
      recorded. RESULTS: Participants (n=53) varied in experience (1-23 years) and hand
      size. Combined median (IQR) leak was 14 (2-46)% and was not different among the
      holds. CONCLUSIONS: There was no difference in the leak measured using the three
      different mask holds.

PMID- 24132717
TI  - Improvement of left ventricular diastolic function and left atrial reverse
      remodeling after catheter ablation of premature ventricular complexes.
AB  - AIMS: Catheter ablation of premature ventricular complexes (PVC) improves left
      ventricular (LV) systolic performance in certain patients; however, the effect on
      diastolic function and left atrial (LA) remodeling is unclear. We assessed the
      effects of catheter ablation of PVCs on parameters of LV diastolic function and
      LA remodeling. METHODS: Forty-seven patients (age 65 +/- 10 years, 46 men) who
      underwent catheter ablation for symptomatic PVCs were evaluated using two
      dimensional echocardiography before and 6 +/- 2 months after ablation. The
      measured diastolic indices included mitral inflow parameters (E wave, A wave, E/A
      ratio, and deceleration time (DT)), mitral lateral annulus early diastolic
      velocity (Ea), and E/Ea ratio. The LA volume was measured using modified biplane
      Simpson's method. We also compared the changes in the left atrial volumes and
      left atrial volume index (LAVI) after PVC ablation. RESULTS: After catheter
      ablation of PVCs, the mean LV ejection fraction (EF) increased significantly
      (49.9 +/- 10.3 vs. 42.8 +/- 11.8, p < 0.01). Significant improvement was also
      seen in A wave velocity (71.3 +/- 17.1 vs. 59.5 +/- 15.1 cm/s, p = 0.039), E/A
      ratio (1.42 +/- 0.6 vs. 1.07 +/- 0.5 ml, p = 0.034), Ea (8.9 +/- 3.9 vs. 6.8 +/-
      2.9 cm/s, p = 0.04), and E/Ea ratio (15.4 +/- 5.8 vs. 10.6 +/- 3.4, p = 0.027),
      whereas mitral E and DT did not show significant change. LAVI decreased
      significantly after ablation (44.4 +/- 14.8 vs. 36.7 +/- 12.5, p < 0.001).
      Significant improvement in LAVI was also seen in patients with normal baseline
      LVEF (p = 0.04). CONCLUSION: Catheter ablation of PVCs improved LV diastolic
      function and resulted in left atrial reverse remodeling.

PMID- 24132718
TI  - Surgical interventions for the early management of Bell's palsy.
AB  - BACKGROUND: Bell's palsy is an acute paralysis of one side of the face of unknown
      aetiology. Bell's palsy should only be used as a diagnosis in the absence of all
      other pathology. As the proposed pathophysiology is swelling and entrapment of
      the nerve, some surgeons suggest surgical decompression of the nerve as a
      possible management option. This is an update of a review first published in
      2011. OBJECTIVES: To assess the effects of surgery in the management of Bell's
      palsy. SEARCH METHODS: On 29 October 2012, we searched the Cochrane Neuromuscular
      Disease Group Specialized Register, CENTRAL (2012, Issue 10), MEDLINE (January
      1966 to October 2012) and EMBASE (January 1980 to October 2012). We also
      handsearched selected conference abstracts for the original version of the
      review. SELECTION CRITERIA: We included all randomised or quasi-randomised
      controlled trials involving any surgical intervention for Bell's palsy. We
      compared surgical interventions to no treatment, sham treatment, other surgical
      treatments or medical treatment. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed whether trials identified from the searches were eligible
      for inclusion. Two review authors independently assessed the risk of bias and
      extracted data. MAIN RESULTS: Two trials with a total of 69 participants met the
      inclusion criteria. The first study considered the treatment of 403 people but
      only included 44 participants in the surgical trial, who were randomised into
      surgical and non-surgical groups. However, the report did not provide information
      on the method of randomisation. The second study randomly allocated 25
      participants into surgical or control groups using statistical charts. There was
      no attempt in either study to conceal allocation. Neither participants nor
      outcome assessors were blind to the interventions, in either study. The first
      study lost seven participants to follow-up and there were no losses to follow-up
      in the second study.Surgeons in both studies decompressed the nerves of all the
      surgical group participants using a retroauricular approach. The primary outcome
      was recovery of facial palsy at 12 months. The first study showed that the
      operated group and the non-operated group (who received oral prednisolone) had
      comparable facial nerve recovery at nine months. This study did not statistically
      compare the groups but the scores and size of the groups suggested that
      statistically significant differences are unlikely. The second study reported no
      statistically significant differences between the operated and control (no
      treatment) groups. One operated participant in the first study had 20 dB
      sensorineural hearing loss and persistent vertigo. We identified no new studies
      when we updated the searches in October 2012. AUTHORS' CONCLUSIONS: There is only
      very low quality evidence from randomised controlled trials and this is
      insufficient to decide whether surgical intervention is beneficial or harmful in
      the management of Bell's palsy.Further research into the role of surgical
      intervention is unlikely to be performed because spontaneous recovery occurs in
      most cases.

PMID- 24132719
TI  - Determination of amino acid neurotransmitters in rat hippocampi by HPLC-UV using
      NBD-F as a derivative.
AB  - A simple, rapid and accurate high-performance liquid chromatography method with
      ultraviolet-visible detection was developed for the determination of five amino
      acid neurotransmitters - aspartate, glutamic acid, glycine, taurine and gamma
      aminobutyric acid - in rat hippocampi with pre-column derivatization with 4
      fluoro-7-nitrobenzofurazan. Several conditions which influenced derivatization
      and separation, such as pH, temperature, acetonitrile percentage mobile phase and
      flow rate, were optimized to obtain a suitable protocol for amino acids
      quantification in samples. The separation of the five neurotransmitter
      derivatives was performed on a C18 column using a mobile phase consisting of
      phosphate buffer (0.02 mol/L, pH 6.0)-acetonitrile (84:16, v/v) at a flow rate of
      1.0 mL/min with the column temperature at 30 degrees C. The detection wavelength
      was 472 nm. Without gradient elution, the five neurotransmitter derivatives were
      completely separated within 15 min. The linear relation was good in the range
      from 0.50 to 500 umol/L, and the correlation coefficients were >=0.999. Intra-day
      precision was between 1.8 and 3.2%, and inter-day precision was between 2.4 and
      4.7%. The limits of detection (signal-to-noise ratio 3) were from 0.02 to 0.15
      umol/L. The established method was used to determine amino acid neurotransmitters
      in rat hippocampi with satisfactory recoveries varying from 94.9 to 105.2%.

PMID- 24132720
TI  - Engineered retroviral virus-like particles for receptor targeting.
AB  - Retroviral gag proteins, as well as fragments minimally containing the capsid
      (CA) and nucleocapsid (NC) subunits of Gag, are able to spontaneously assemble
      into virus-like particles (VLPs). This occurs in mammalian and bacterial cells as
      well as in in vitro systems. In every circumstance, nucleic acids are
      incorporated into the forming particles. Here, we took advantage of an in vitro
      system for the generation of non-enveloped Mason-Pfizer monkey virus (M-PMV) VLPs
      derived from a self-assembling CA-NC subunit of Gag. These VLPs were modified
      through N-terminal extension of CA-NC with short oligopeptides that, after the
      assembly process, were exposed on the surface of VLPs. The employed N-terminal
      modifications allowed specific interaction with target cells expressing prostate
      specific membrane antigen. Using this system, we were able to incorporate
      selected siRNA into forming VLPs and deliver it into the cytosol of target cells.
      In comparison with other viral vectors designed for targeted transgene delivery,
      this M-PMV VLP system represents the lowest risk of generating virus-associated
      pathology, as the VLPs do not contain any viral coding sequences and are formed
      in a cell-free system. 

PMID- 24132721
TI  - Comparative analysis of antibody induction and protection against influenza virus
      infection by DNA immunization with HA, HAe, and HA1 in mice.
AB  - Plasmid DNA vaccines are considered alternatives to inactivated influenza virus
      vaccines to control influenza. Vaccination with a hemagglutinin (HA)-, HA
      ectodomain (HAe)-, or HA subunit 1 (HA1)-based vaccine can stimulate protective
      immunity in animals. The aim of this study was to compare their capacity to
      induce an antibody response and protection against influenza virus infection in
      mice after DNA vaccination. We constructed three expression vectors encoding full
      length HA, HAe, or HA1 of the A/California/07/2009 influenza A virus and designed
      three animal experiments: (i) BALB/c mice were immunized twice with 30 MUg of the
      HA, HAe, or HA1 DNA vaccine with high-voltage electroporation (100 V), and 3
      weeks after boosting, they were challenged with a lethal dose of virus. (ii)
      Immunization and challenge were as in experiment i, but with low-voltage
      electroporation (10 V). (iii) Mice were immunized once with 50 MUg of DNA and
      challenged 1 week later. The immunogenic effects of the three DNA vaccines were
      evaluated in terms of antibody titer, survival rate, bodyweight change, and lung
      viral titer. In all three experiments, both HA and HAe induced higher antibody
      and neutralization titers than HA1. Following challenge with a lethal mouse
      adapted homologous virus, both HA and HAe reduced the viral titers in lung washes
      or offered better protection from weight loss than HA1 in experiments ii and iii.
      Thus, HA1 induces a lower immune response than HA or HAe when used as a DNA
      vaccination. Our data should be valuable in choosing the optimal candidate
      vaccine when faced with the threat of pandemic influenza. 

PMID- 24132723
TI  - Does the cognitive reflection test measure cognitive reflection? A mathematical
      modeling approach.
AB  - We used a mathematical modeling approach, based on a sample of 2,019
      participants, to better understand what the cognitive reflection test (CRT;
      Frederick In Journal of Economic Perspectives, 19, 25-42, 2005) measures. This
      test, which is typically completed in less than 10 min, contains three problems
      and aims to measure the ability or disposition to resist reporting the response
      that first comes to mind. However, since the test contains three mathematically
      based problems, it is possible that the test only measures mathematical
      abilities, and not cognitive reflection. We found that the models that included
      an inhibition parameter (i.e., the probability of inhibiting an intuitive
      response), as well as a mathematical parameter (i.e., the probability of using an
      adequate mathematical procedure), fitted the data better than a model that only
      included a mathematical parameter. We also found that the inhibition parameter in
      males is best explained by both rational thinking ability and the disposition
      toward actively open-minded thinking, whereas in females this parameter was
      better explained by rational thinking only. With these findings, this study
      contributes to the understanding of the processes involved in solving the CRT,
      and will be particularly useful for researchers who are considering using this
      test in their research. 

PMID- 24132724
TI  - Genetic profile characterization and population study of 21 autosomal STR in
      Chinese Kazak ethnic minority group.
AB  - Short tandem repeat loci have been recognized as useful tools in the routine
      forensic application and in recent decades, more and more new short tandem repeat
      (STR) loci have been constantly discovered, studied, and applied in forensic
      caseworks. In this study, we investigated the genetic polymorphisms of 21 STR
      loci in the Kazak ethnic minority as well as the genetic relationships between
      the Kazak ethnic minority and other populations. Allelic frequencies of 21 STR
      loci were obtained from 114 unrelated healthy Kazak individuals in the Ili Kazak
      Autonomous Prefecture, Xinjiang Uigur Autonomous Region of China. We observed a
      total of 159 alleles in the group with the allelic diversity values ranging from
      0.0044 to 0.5088. The highest polymorphism was found at D19S433 locus and the
      lowest was found at D1S1627. Statistical analysis of the generated data indicated
      no deviation from Hardy-Weinberg equilibriums at all 21 STR loci. In order to
      estimate the population differentiation, allelic frequencies of all STR loci of
      the Kazak were compared with those of other neighboring populations using
      analysis of molecular variance method. Statistically significant differences were
      found between the studied population and other populations at 2-7 STR loci. A
      neighbor-joining tree was constructed based on allelic frequencies of the 21 STR
      loci and phylogenetic analysis indicates that the Kazak has a close genetic
      relationship with the Uigur ethnic group. The present results may provide useful
      information for forensic sciences and population genetics studies, and can also
      increase our understanding of the genetic background of this group. The present
      findings showed that all the 21 STR loci are highly genetically polymorphic in
      the Kazak group, which provided valuable population genetic data for the genetic
      information study, forensic human individual identification, and paternity tests.

PMID- 24132725
TI  - Oxidative stress in cystic fibrosis patients with Burkholderia cenocepacia airway
      colonization: relation of 8-isoprostane concentration in exhaled breath
      condensate to lung function decline.
AB  - The association between oxidative stress and neutrophilic inflammation in cystic
      fibrosis (CF) lung disease is well recognized. 8-Isoprostane is a product of non
      enzymatic oxidation of arachidonic acid. The aim of the present study was to
      examine the relationship between lung function decline and 8-isoprostane
      concentrations in exhaled breath condensate (EBC) in CF patients with
      Burkholderia cenocepacia airway colonization. Concentrations of 8-isoprostane in
      EBC were measured in 24 stable CF patients with B. cenocepacia airway
      colonization. The median (interquartile range) age of the cohort was 23.9 (22.0;
      26.6) years. All patients underwent clinical examinations and pulmonary function
      tests at the time of EBC collection and in 1-, 3-, and 5-year intervals. 8
      Isoprostane concentrations in EBC correlated to 1- and 3-year declines of forced
      expiratory volume in 1 s (FEV1) with r(S) values of -0.511 (p = 0.0011) and 
      0.495 (p = 0.016), respectively. In multiple regression analysis, 8-isoprostane
      concentrations in EBC were the only independent predictor for 1-year FEV1 decline
      (p = 0.01). When the median value of 8-isoprostane concentration in EBC (10.0
      pg/mL) was used as a cutoff, subgroups of patients with lower and higher level of
      oxidative stress had significantly different median (interquartile range) FEV1
      declines in 1-year interval, -2.4% (-5.3; 0.8) and -7.3% (-10.3; -5.8) predicted
      (p = 0.009). In conclusion, 8-isoprostane concentrations in EBC correlated to
      short-term lung function decline in CF patients with B. cenocepacia airway
      colonization. This correlation reflects the role of oxidative stress in CF lung
      pathogenesis and contributes to prediction of prognosis in these patients.

PMID- 24132727
TI  - Visualizing aquatic bacteria by light and transmission electron microscopy.
AB  - The understanding of the functional role of aquatic bacteria in microbial food
      webs is largely dependent on methods applied to the direct visualization and
      enumeration of these organisms. While the ultrastructure of aquatic bacteria is
      still poorly known, routine observation of aquatic bacteria by light microscopy
      requires staining with fluorochromes, followed by filtration and direct counting
      on filter surfaces. Here, we used a new strategy to visualize and enumerate
      aquatic bacteria by light microscopy. By spinning water samples from varied
      tropical ecosystems in a cytocentrifuge, we found that bacteria firmly adhere to
      regular slides, can be stained by fluorochoromes with no background formation and
      fast enumerated. Significant correlations were found between the
      cytocentrifugation and filter-based methods. Moreover, preparations through
      cytocentrifugation were more adequate for bacterial viability evaluation than
      filter-based preparations. Transmission electron microscopic analyses revealed a
      morphological diversity of bacteria with different internal and external
      structures, such as large variation in the cell envelope and capsule thickness,
      and presence or not of thylakoid membranes. Our results demonstrate that aquatic
      bacteria represent an ultrastructurally diverse population and open avenues for
      easy handling/quantification and better visualization of bacteria by light
      microscopy without the need of filter membranes. 

PMID- 24132728
TI  - Halococcus sediminicola sp. nov., an extremely halophilic archaeon isolated from
      a marine sediment.
AB  - A novel, red-pigmented and coccoid haloarchaeon, designated strain CBA1101(T),
      was isolated from a marine sediment. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain CBA1101(T) is most closely related to the genus
      Halococcus in the family Halobacteriaceae. Strain CBA1101(T) had a highest 16S
      rRNA gene sequence similarity of 98.4 % with Halococcus dombrowskii DSM 14522(T),
      followed by 93.7-98.3 % with sequences of other type strains in the genus
      Halococcus. The RNA polymerase subunit B' gene sequence similarity of strain
      CBA1101(T) with that of Halococcus qingdaonensis JCM 13587(T) is 89.5 % and lower
      with those of other members of the genus Halococcus. Strain CBA1101(T) was
      observed to grow at 25-40  degrees C, pH 6.0-9.0 and in the presence of 15-30 %
      (w/v) NaCl, with optimal growth at 35-40  degrees C, pH 7.0 and with 20 % NaCl.
      The cells of strain CBA1101(T) are Gram-negative and did not lyse in distilled
      water. The major polar lipids were identified as phosphatidylglyerol,
      phosphatidylglycerol phosphate methyl ester, sulfated diglycosyl diether,
      unidentified phospholipids and unidentified glycolipids. The genomic DNA G+C
      content was determined 66.0 mol%. The DNA-DNA hybridization experiment showed
      that there was less than 40 % relatedness between strain CBA1101(T) and the
      reference species in the genus Halococcus. Based on this polyphasic taxonomic
      analysis, strain CBA1101(T) is considered to represent a new species in the genus
      Halococcus, for which the name Halococcus sediminicola sp. nov. is proposed. The
      type strain is CBA1101(T) (=JCM 18965(T) = CECT 8275(T)). 

PMID- 24132726
TI  - Skeletal manifestations of treatment of breast cancer.
AB  - Breast cancer and osteoporosis are common diagnoses in women. Breast cancer
      survival has improved due to earlier detection and improved treatments. As most
      breast cancers are estrogen receptor positive, treatment is often aimed at
      altering the hormonal environment. Both pre and postmenopausal women undergoing
      these therapies are at risk for bone loss. The patient's health care team ought
      to have an awareness of the potential for breast cancer treatments to accelerate
      bone loss. Women with early stage breast cancer are treated with curative intent
      and, therefore, maintaining bone health is important and is part of the
      survivorship care to ensure an optimal quality of life. 

PMID- 24132729
TI  - Thalassomonas fusca sp. nov., a novel gammaproteobacterium isolated from tidal
      flat sediment.
AB  - A Gram-negative, aerobic, non-motile, dark brown-coloured and rod-shaped
      bacterial strain, designated G-MB1(T), was isolated from a tidal flat sediment of
      the South Sea, South Korea. Strain G-MB1(T) was found to grow optimally at 25 
      degrees C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. A neighbour
      joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain G
      MB1(T) fell within the clade comprising Thalassomonas species, clustering with
      the type strains of Thalassomonas agarivorans, Thalassomonas loyana,
      Thalassomonas ganghwensis and Thalassomonas agariperforans, with which it
      exhibited 16S rRNA gene sequence similarity values of 96.0-96.9 %. The 16S rRNA
      gene sequence similarity values between strain G-MB1(T) and the type strains of
      the other Thalassomonas species were 94.6-95.1 %. Strain G-MB1(T) was found to
      contain Q-8 as the predominant ubiquinone and C16:0, C17:1 omega8c, C16:1
      omega9c, C12:0 3-OH and summed feature 3 (C16:1 omega7c and/or C16:1 omega6c) as
      the major fatty acids. The major polar lipids of strain G-MB1(T) were
      phosphatidylglycerol, phosphatidylethanolamine and one unidentified aminolipid.
      The DNA G+C content of strain G-MB1(T) was determined to be 42.4 mol%.
      Differential phenotypic properties, together with the phylogenetic
      distinctiveness, revealed that strain G-MB1(T) is separated from other
      Thalassomonas species. On the basis of the data presented, strain G-MB1(T) is
      considered to represent a novel species of the genus Thalassomonas, for which the
      name Thalassomonas fusca sp. nov. is proposed. The type strain is G-MB1(T) (=KCTC
      32499(T) = NBRC 109830(T)). 

PMID- 24132730
TI  - Levator plate descent correlates with levator ani muscle deficiency.
AB  - AIMS: Measurements such as the minimal levator hiatus dimension, levator plate
      angle, iliococcygeal angle, and anorectal angle have been used for assessing the
      impact of levator damage on static and dynamic imaging features. The primary aim
      of this study was to investigate the association between levator ani muscle
      deficiency (LAD) and the position of the levator plate. METHODS: 3D endovaginal
      ultrasounds of 186 women were reviewed. The levator ani muscle groups, the
      puboanalis, puborectalis, and pubovisceralis, were scored for abnormalities, (0
      no defect and 3 total absence of the muscle). The levator plate descent angle,
      minimal levator hiatus dimensions, and the anorectal angle were measured. Levator
      plate descent towards the perineum was assessed and correlated with levator ani
      muscle deficiency. RESULTS: The correlation between puborectalis scores and
      minimal levator hiatus area, anorectal angle and levator plate descent angle were
      0.43 (P < 0.0001), 0.22 (P = 0.0045), and -0.40 (P < 0.0001), respectively. The
      correlation between pubovisceralis scores and minimal levator hiatus area,
      anorectal angle and levator plate descent angle were 0.36 (P < 0.0001), 0.38 (P <
      0.0001), and -0.40 (P < 0.0001), respectively. The correlation between the total
      levator ani muscle scores and the minimal levator hiatus area, anorectal angle
      and the levator plate descent angle were 0.45 (P < 0.0001), 0.31 (P < 0.0001),
      and -0.45 (P < 0.0001) respectively. CONCLUSION: Worsening LAD score is
      associated with levator plate descensus and with decreasing levator plate descent
      angle. We can use levator plate descent angle along with the minimal levator
      hiatus and anorectal angle as objective measurements to assess levator ani muscle
      deficiency.

PMID- 24132731
TI  - Separation of total lipids on human lipoproteins using surfactant-coated
      multiwalled carbon nanotubes as pseudostationary phase in capillary
      electrophoresis.
AB  - Surfactant-coated multiwalled carbon nanotubes (MWNTs) were used as
      pseudostationary phase (PSP) in CE to investigate the total lipids of high
      density lipoproteins and low-density lipoproteins. To optimize the CE conditions,
      several experimental factors including carbon nanotube concentration, bile salt
      concentration, sodium phosphate (PB) concentration, organic modifier
      concentration and buffer pH value have been examined. In addition, the CE
      capillary temperature and applied voltage have also been examined. The optimal
      separation buffer selected was a mixture of 3.2 mg/L MWNT, 50 mM bile salt, 10 mM
      PB, 20% 1-propanol, pH 9.5. The optimal capillary temperature and applied voltage
      selected were 50 degrees C and 20 kV, respectively. Phosphatidyl choline (PC) has
      been used as a model analyte and investigated by the optimal CE method. The
      linear range for PC was 0.1-3 mg/mL with a correlation coefficient of 0.9934, and
      the concentration LOD was 0.055 mg/mL. The optimal CE method has been used to
      characterize the total lipids of high-density lipoprotein and low-density
      lipoprotein. At absorbance 200 nm, one major peak and two or three minor peaks
      showed for the total lipids of lipoproteins within 13 minutes. Resolutions of the
      total lipids were enhanced using surfactant-coated MWNTs as PSPs in the CE
      separation buffer. However, resolutions of the total lipids were not enhanced
      using surfactant-coated single-walled carbon nanotubes as PSPs in the CE
      separation buffer.

PMID- 24132732
TI  - Attention network hypoconnectivity with default and affective network
      hyperconnectivity in adults diagnosed with attention-deficit/hyperactivity
      disorder in childhood.
AB  - IMPORTANCE: The neurobiological underpinnings of attention-deficit/hyperactivity
      disorder (ADHD) and particularly those associated with the persistence of ADHD
      into adulthood are not yet well understood. The correlation patterns in
      spontaneous neural fluctuations at rest are known as resting-state functional
      connectivity (RSFC) and could characterize ADHD-specific connectivity changes.
      OBJECTIVE: To determine the specific location of possible ADHD-related
      differences in RSFC between adults diagnosed as having ADHD in childhood and
      control subjects. DESIGN Using resting-state functional magnetic resonance
      imaging, we calculated and compared functional connectivity from attention,
      affective, default, and cognitive control networks involved in the
      psychopathology of ADHD between the ADHD and control groups. SETTING University
      psychiatric service and magnetic resonance imaging research center. PARTICIPANTS:
      Sixteen drug-free adults (5 women and 11 men; mean age, 24.5 years) diagnosed
      with combined-type ADHD in childhood and 16 healthy controls matched for age
      (mean age, 24.4 years), sex, handedness, and educational level recruited from the
      community. INTERVENTION: Functional magnetic resonance imaging. MAIN OUTCOMES AND
      MEASURES: Connectivity data from ventral and dorsal attention, affective,
      default, and cognitive control networks and ADHD symptoms derived from ADHD
      specific rating instruments. RESULTS: Adults with ADHD showed significantly
      decreased RSFC within the attention networks and increased RSFC within the
      affective and default mode and the right lateralized cognitive control networks
      compared with healthy controls (P < .01, familywise error for whole-brain cluster
      correction). Lower RSFC in the ventral and dorsal attention network was
      significantly correlated with higher levels of ADHD symptoms (P < .001).
      CONCLUSIONS AND RELEVANCE: These RSFC findings might underpin a biological basis
      for adult ADHD and are functionally related to persistent inattention,
      disturbance in cognitive control, and emotional dysregulation in adults with
      ADHD. These findings need to be understood in the context of all aspects of brain
      function in ADHD.

PMID- 24132733
TI  - Treating substance use disorders in the criminal justice system.
AB  - The large number of individuals with substance use disorders involved in the
      nation's criminal justice system (CJS) represents a unique opportunity, as well
      as challenges, in addressing the dual concerns of public safety and public
      health. Unfortunately, a low proportion of those who could benefit from treatment
      actually receive it while involved in the CJS. This article presents a review of
      recent research on the effectiveness of major substance abuse treatment
      interventions used at different possible linkage points during criminal justice
      case processing, including diversion, jail, prison, and community supervision.
      This is followed by a discussion of key research and practice issues, including
      low rates of treatment access and under-utilization of medication-assisted
      treatment. Concluding comments discuss principles of effective treatment for
      offenders and identify key gaps in research and practice that need to be
      addressed to improve and expand provision of effective treatment for offenders. 

PMID- 24132734
TI  - Predictors of disease progression in pediatric dilated cardiomyopathy.
AB  - BACKGROUND: Despite medical advances, children with dilated cardiomyopathy (DCM)
      remain at high risk of death or need for cardiac transplantation. We sought to
      identify predictors of disease progression in pediatric DCM. METHODS AND RESULTS:
      The Pediatric Heart Network evaluated chronic DCM patients with prospective
      echocardiographic and clinical data collection during an 18-month follow-up.
      Inclusion criteria were age <22 years and DCM disease duration >2 months.
      Patients requiring intravenous inotropic/mechanical support or listed status
      1A/1B for transplant were excluded. Disease progression was defined as an
      increase in transplant listing status, hospitalization for heart failure,
      intravenous inotropes, mechanical support, or death. Predictors of disease
      progression were identified using Cox proportional hazards modeling and
      classification and regression tree analysis. Of the 127 patients, 28 (22%) had
      disease progression during the 18-month follow-up. Multivariable analysis
      identified older age at diagnosis (hazard ratio=1.14 per year; P<0.001), larger
      left ventricular (LV) end-diastolic M-mode dimension z-score (hazard ratio=1.49;
      P<0.001), and lower septal peak systolic tissue Doppler velocity z-score (hazard
      ratio=0.81; P=0.01) as independent predictors of disease progression.
      Classification and regression tree analysis stratified patients at risk of
      disease progression with 89% sensitivity and 94% specificity based on LV end
      diastolic M-mode dimension z-score >=7.7, LV ejection fraction <39%, LV inflow
      propagation velocity (color M-mode) z-score <-0.28, and age at diagnosis >=8.5
      months. CONCLUSIONS: In children with chronic stable DCM, a combination of
      diagnosis after late infancy and echocardiographic parameters of larger LV size
      and systolic and diastolic function predicted disease progression. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00123071.

PMID- 24132735
TI  - Distribution of metastatic sites in patients with prostate cancer: A population
      based analysis.
AB  - BACKGROUND: There is few data on what constitutes the distribution of metastatic
      sites in prostate cancer (PCa). The aim of our study was to systematically
      describe the most common sites of metastases in a contemporary cohort of PCa
      patients. METHODS: Patients with metastatic PCa were abstracted from the
      Nationwide Inpatient Sample (1998-2010). Most common metastatic sites within the
      entire population were described. Stratification was performed according to the
      presence of single or multiple (>= 2 sites) metastases. Additionally, we
      evaluated the distribution of metastatic sites amongst patients with and without
      bone metastases. RESULTS: Overall, 74,826 patients with metastatic PCa were
      identified. The most common metastatic sites were bone (84%), distant lymph nodes
      (10.6%), liver (10.2%), and thorax (9.1%). Overall, 18.4% of patients had
      multiple metastatic sites involved. When stratifying patients according to the
      site of metastases, only 19.4% of men with bone metastases had multiple sites
      involved. Conversely, among patients with lymph nodes, liver, thorax, brain,
      digestive system, retroperitoneum, and kidney and adrenal gland metastases the
      proportion of men with multiple sites involved was 43.4%, 76.0%, 76.7%, 73.0%,
      52.2%, 60.9%, and 76.4%, respectively. When focusing exclusively on patients with
      bone metastases, the most common sites of secondary metastases were liver
      (39.1%), thorax (35.2%), distant lymph nodes (24.6%), and brain (12.4%).
      CONCLUSIONS: Although the majority of patients with metastatic PCa experience
      bone location, the proportion of patients with atypical metastases is not
      negligible. These findings might be helpful when planning diagnostic imaging
      procedures in patients with advanced PCa.

PMID- 24132736
TI  - Evaluation of pharmaceutical care in a diabetes ward from China: a pre-and post
      intervention study.
AB  - OBJECTIVE: To describe the development and implementation of pharmaceutical care
      services in a diabetes ward, and to examine the effectiveness of pharmacist
      interventions. SETTING: Tongde hospital of Zhejiang province, a 1,200-bed South
      China teaching hospital, serving the local community. METHOD: A single-center, 2
      phase (pre-/post-intervention phase) designs was performed in the diabetes ward
      of a general hospital. Patients in post-intervention phase (October 2012 to
      December 2012) received pharmaceutical care from a clinical pharmacist, while
      patients in the pre-intervention phase (January 2012 to March 2012) received
      routine medical care. The pre- and post-intervention phases were then compared to
      evaluate the outcomes of pharmacist interventions. Main outcome measure type and
      number of interventions, and medication errors assessed at the baseline and at
      the end of pharmaceutical care were the main outcome measures. RESULTS: During
      the 3-month study period, the clinical pharmacist made 240 interventions for 473
      admitted patients; of these, 207 (86.3 %) were accepted by physicians or nurses,
      and dosage adjustment [n = 83, (34.6 %)] was the type of intervention implemented
      most often. In the group that received the participation of pharmacists,
      medication errors per patient decreased from 1.68 to 0.46 (p < 0.001); medication
      errors, of incorrect dose or dosing interval, were markedly improved (decreased
      from 0.87 to 0.14; p < 0.001), the drug cost per patient day decreased from
      $347.15 to $309.74 (p = 0.095), and the length of diabetes ward stay did not
      change significantly (16.14 vs. 15.93 days; p = 0.15). CONCLUSION: The presence
      of the pharmacist in the diabetes ward resulted in significant reduction in
      medication errors and had potential drug-cost-saving effects.

PMID- 24132737
TI  - A matched case-control study of IBD-associated colorectal cancer: IBD portends
      worse outcome.
AB  - BACKGROUND AND OBJECTIVES: The effect of inflammatory bowel disease (IBD) on
      outcome in patients with colorectal cancer (CRC) remains unclear. Our objective
      is to evaluate oncologic outcomes of patients with IBD-associated CRC. METHODS:
      We retrospectively reviewed a prospectively maintained database to identify
      patients with IBD-associated CRC. Clinicopathologic variables and overall
      survival were compared to patients with sporadic CRC using a 2:1 matched
      controlled analysis. RESULTS: Fifty-five patients with IBD and CRC were
      identified. On univariate analysis, CRC patients with IBD had a significantly
      shorter median overall survival (68.2 months vs. 204.3 months, P = 0.01) compared
      to patients with sporadic CRC. On multivariate analysis, after adjusting for N
      and M stage, IBD was associated with an increased risk of death compared to
      sporadic CRC (HR = 2.011, 95% CI 1.24-3.23, P = 0.004). Stage 3 CRC patients with
      IBD in particular showed significantly decreased survival (23.0 vs. 133.9 months,
      P = 0.008). CONCLUSIONS: In this study, patients with node-positive IBD
      associated CRC had a significant increased risk of death and a shorter overall
      survival than those with sporadic disease and may require tailored adjuvant
      therapy and surveillance protocols. Continued investigation to elucidate the
      mechanisms that contribute to these observations is justified.

PMID- 24132738
TI  - Mapping the low palmitate fap1 mutation and validation of its effects in soybean
      oil and agronomic traits in three soybean populations.
AB  - KEY MESSAGE: fap 1 mutation is caused by a G174A change in GmKASIIIA that
      disrupts a donor splice site recognition and creates a GATCTG motif that enhanced
      its expression. Soybean oil with reduced palmitic acid content is desirable to
      reduce the health risks associated with consumption of this fatty acid. The
      objectives of this study were: to identify the genomic location of the reduced
      palmitate fap1 mutation, determine its molecular basis, estimate the amount of
      phenotypic variation in fatty acid composition explained by this locus, determine
      if there are epistatic interactions between the fap1 and fap nc loci and,
      determine if the fap1 mutation has pleiotropic effects on seed yield, oil and
      protein content in three soybean populations. This study detected two major QTL
      for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near
      BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the
      variation in 16:0 content in the three populations. Sequencing results of a
      putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the
      germplasm line C1726, which was predicted to disrupt the donor splice site
      recognition between exon one and intron one and produce a truncated KASIIIA
      protein. This G to A change also created the GATCTG motif that enhanced gene
      expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA
      mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and
      an increase in unsaturated fatty acids content. There were significant epistatic
      interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and
      seed yield in two populations. In conclusion, the fap1 phenotype is caused by a
      single unique SNP in the GmKASIIIA gene.

PMID- 24132739
TI  - Going out on a limb about regrowing an arm.
AB  - Starting with the observations that fetuses effortlessly grow limbs, fetuses heal
      wounds without scar and children up to the age of two can partially regrow
      amputated digits, the potential for adult humans to regrow limbs is explored. The
      process of limb growth in amphibians is reviewed with these steps summarizing the
      process: blood vessels contract to minimize bleeding; the injury site is covered
      by skin cells transforming into the apical epithelial cap which sends signals
      important for the next phases of the regrowth; resident fibroblasts leave the
      surrounding extracellular matrix and migrate across the amputation surface;
      migratory fibroblasts proliferate and dedifferentiate to form an aggregation of
      stemlike cells called the blastema; and the blastema coordinates the formation of
      a new limb. Other factors contributing to this process are: innervation, cell
      spatial "memory," chemical signals between cells, gene up and down regulation,
      cell differentiation (or dedifferentiation) and inflammatory cells. Remarkable
      discoveries have been made in all these areas in the last few years that might be
      integrated into technology for limb regeneration. In particular, the
      demonstration of the plasticity of supposedly "terminally differentiated" cells
      speak to the idea that mature cells at the amputation site might be harnessed for
      limb regrowth. Also, the demonstration that macrophages can be driven to a
      regenerative phenotype (M2) and they may also be stem-like is promising for
      complex regenerations. This article posits that scientific discoveries useful for
      limb regeneration have been made and now it is time to develop technology
      exploiting these discoveries to regrow limbs. 

PMID- 24132740
TI  - Reply to Stan Becker, "has the world really survived the population bomb?
      (Commentary on "how the world survived the population bomb: lessons from 50 years
      of extraordinary demographic history")".

PMID- 24132741
TI  - Comment of Liying Luo's article, "assessing validity and application scope of the
      intrinsic estimator approach to the age-period-cohort problem".

PMID- 24132742
TI  - Cohort analysis' unholy quest: a discussion.

PMID- 24132743
TI  - Misunderstandings, mischaracterizations, and the problematic choice of a specific
      instance in which the IE should never be applied.

PMID- 24132744
TI  - Comment on "assessing validity and application scope of the intrinsic estimator
      approach to the age-period-cohort (APC) problem".

PMID- 24132745
TI  - Vitamin D: too soon to turn out the lights?

PMID- 24132751
TI  - Regulation of the high-affinity copper transporter (hCtr1) expression by
      cisplatin and heavy metals.
AB  - Platinum-based antitumor agents have been the mainstay in cancer chemotherapy for
      many human malignancies. Drug resistance is an important obstacle to achieving
      the maximal therapeutic efficacy of these drugs. Understanding how platinum drugs
      enter cells is of great importance in improving therapeutic efficacy. It has been
      demonstrated that human high-affinity copper transporter 1 (hCtr1) is involved in
      transporting cisplatin into cells to elicit cytotoxic effects, although other
      mechanisms may exist. In this communication, we demonstrate that cisplatin
      transcriptionally induces the expression of hCtr1 in time- and concentration
      dependent manners. Cisplatin functions as a competitor for hCtr1-mediated copper
      transport, resulting in reduced cellular copper levels and leading to upregulated
      expression of Sp1, which is a positive regulator for hCtr1 expression. Thus,
      regulation of hCtr1 expression by cisplatin is an integral part of the copper
      homeostasis regulation system. We also demonstrate that Ag(I) and Zn(II), which
      are known to suppress hCtr1-mediated copper transport, can also induce hCtr1/Sp1
      expression. In contrast, Cd(II), another inhibitor of copper transport,
      downregulates hCtr1 expression by suppressing Sp1 expression. Collectively, our
      results demonstrate diverse mechanisms of regulating copper metabolism by these
      heavy metals. 

PMID- 24132752
TI  - Di- and polynuclear silver(I) saccharinate complexes of tertiary diphosphane
      ligands: synthesis, structures, in vitro DNA binding, and antibacterial and
      anticancer properties.
AB  - A series of new silver(I) saccharinate (sac) complexes, [Ag2(sac)2(MU
      dppm)H2O].H2O (1), {[Ag2(MU-sac)2(MU-dppe)].3H2O.CH2Cl2} n (2), [Ag2(MU-sac)2(MU
      dppp)] n (3), and [Ag(sac)(MU-dppb)] n (4) [dppm is 1,1
      bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is
      1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane],
      have been synthesized and characterized by C, H, N elemental analysis, IR
      spectroscopy, (1)H NMR, (13)C NMR, and (31)P NMR spectroscopy, electrospray
      ionization mass spectrometry, and thermogravimetry-differential thermal analysis.
      Single-crystal X-ray studies show that the diphosphanes act as bridging ligands
      to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and
      4), whereas the sac ligand adopts a MU2-N/O bridging mode in 2, and is N
      coordinated in 1 and 4. The interaction of the silver(I) complexes with fish
      sperm DNA was investigated using UV-vis spectroscopy, fluorescence spectroscopy,
      and agarose gel electrophoresis. The binding studies indicate that the silver(I)
      complexes can interact with fish sperm DNA through intercalation, and complexes 1
      and 3 have the highest binding affinity. The gel electrophoresis assay further
      confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum
      inhibitory concentrations of the complexes indicate that complex 1 exhibits very
      high antibacterial activity against standard bacterial strains of Escherichia
      coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than
      those of AgNO3, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover,
      complexes 1-3 exhibit very high cytotoxic activity against A549 and MCF-7 cancer
      cell lines, compared with AgNO3 and cisplatin. The bacterial and cell growth
      inhibitions of the silver(I) complexes are closely related to their DNA binding
      affinities. 

PMID- 24132753
TI  - Alternative processing as evolutionary mechanism for the origin of novel
      nonprotein coding RNAs.
AB  - The evolution of new genes can ensue through either gene duplication and the
      neofunctionalization of one of the copies or the formation of a de novo gene from
      hitherto nonfunctional, neutrally evolving intergenic or intronic genomic
      sequences. Only very rarely are entire genes created de novo. Mostly,
      nonfunctional sequences are coopted as novel parts of existing genes, such as in
      the process of exonization whereby introns become exons through changes in
      splicing. Here, we report a case in which a novel nonprotein coding RNA evolved
      by intron-sequence recruitment into its structure. cDNAs derived from rat brain
      small RNAs, revealed a novel small nucleolar RNA (snoRNA) originating from one of
      the Snord115 copies in the rat Prader-Willi syndrome locus. We suggest that a
      single-point substitution in the Snord115 region led to the expression of a
      longer snoRNA variant, designated as L-Snord115. Cell culture and footprinting
      experiments confirmed that a single nucleotide substitution at Snord115 position
      67 destabilized the kink-turn motif within the canonical snoRNA, while distal
      intronic sequences provided an alternate D-box region. The exapted sequence
      displays putative base pairing to 28S rRNA and mRNA targets. 

PMID- 24132754
TI  - Emerging role of tumor-associated macrophages as therapeutic targets in patients
      with metastatic renal cell carcinoma.
AB  - Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes
      recruited into the renal cell carcinoma (RCC) microenvironment. In response to
      inflammatory stimuli, macrophages undergo M1 (classical) or M2 (alternative)
      activation. M1 cells produce high levels of inflammatory cytokines, such as tumor
      necrosis factor-alpha, interleukin (IL)-12, IL-23 and IL-6, while M2 cells
      produce anti-inflammatory cytokines, such as IL-10, thus contributing to RCC
      related immune dysfunction. The presence of extensive TAM infiltration in RCC
      microenvironment contributes to cancer progression and metastasis by stimulating
      angiogenesis, tumor growth, and cellular migration and invasion. Moreover, TAMs
      are involved in epithelial-mesenchymal transition of RCC cancer cells and in the
      development of tumor resistance to targeted agents. Interestingly, macrophage
      autophagy seems to play an important role in RCC. Based on this scenario, TAMs
      represent a promising and effective target for cancer therapy in RCC. Several
      strategies have been proposed to suppress TAM recruitment, to deplete their
      number, to switch M2 TAMs into antitumor M1 phenotype and to inhibit TAM
      associated molecules. In this review, we summarize current data on the essential
      role of TAMs in RCC angiogenesis, invasion, impaired anti-tumor immune response
      and development of drug resistance, thus describing the emerging TAM-centered
      therapies for RCC patients.

PMID- 24132755
TI  - Cyanophage and algal virus.

PMID- 24132756
TI  - Freshwater cyanophages.
AB  - Cyanophages are double-stranded DNA viruses that infect cyanobacteria, and they
      can be found in both freshwater and marine environments. They have a complex
      pattern of host ranges and play important roles in controlling cyanobacteria
      population. Unlike marine cyanophages, for which there have been a number of
      recent investigations, very little attention has been paid to freshwater
      cyanophages. This review summarizes the taxonomy and morphology, host range,
      distribution, seasonal dynamics, and complete genomes of freshwater cyanophages,
      as well as diagnostic markers that can be used to identify them. 

PMID- 24132757
TI  - Characterization and genomic analysis of a plaque purified strain of cyanophage
      PP.
AB  - Cyanophages are ubiquitous and essential components of the aquatic environment
      and play an important role in the termination of algal blooms. As such, they have
      attracted widespread interest. PP was the first isolated cyanophage in China,
      which infects Plectonema boryanum and Phormidium foveolarum. In this study, this
      cyanophage was purified three times by a double-agar overlay plaque assay and
      characterized. Its genome was extracted, totally sequenced and analyzed. Electron
      microscopy revealed a particle with an icosahedral head connected to a short
      stubby tail. Bioassays showed that PP was quite virulent. The genome of PP is a
      42,480 base pair (bp), linear, double-stranded DNA molecule with 222 bp terminal
      repeats. It has high similarity with the known Pf-WMP3 sequence. It contains 41
      open reading frames (ORFs), 17 of which were annotated. Intriguingly, the genome
      can be divided into two completely different parts, which differ both in
      orientation and function. 

PMID- 24132758
TI  - Viral metagenomics analysis of planktonic viruses in East Lake, Wuhan, China.
AB  - East Lake (Lake Donghu), located in Wuhan, China, is a typical city freshwater
      lake that has been experiencing eutrophic conditions and algal blooming during
      recent years. Marine and fresh water are considered to contain a large number of
      viruses. However, little is known about their genetic diversity because of the
      limited techniques for culturing viruses. In this study, we conducted a viral
      metagenomic analysis using a high-throughput sequencing technique with samples
      collected from East Lake in Spring, Summer, Autumn, and Winter. The libraries
      from four samples each generated 234,669, 71,837, 12,820, and 34,236 contigs (>
      90 bp each), respectively. The genetic structure of the viral community revealed
      a high genetic diversity covering 23 viral families, with the majority of contigs
      homologous to DNA viruses, including members of Myoviridae, Podoviridae,
      Siphoviridae, Phycodnaviridae, and Microviridae, which infect bacteria or algae,
      and members of Circoviridae, which infect invertebrates and vertebrates. The
      highest viral genetic diversity occurred in samples collected in August, then
      December and June, and the least diversity in March. Most contigs have low
      sequence identities with known viruses. PCR detection targeting the conserved
      sequences of genes (g20, psbA, psbD, and DNApol) of cyanophages further confirmed
      that there are novel cyanophages in the East Lake. Our viral metagenomic data
      provide the first preliminary understanding of the virome in one freshwater lake
      in China and would be helpful for novel virus discovery and the control of algal
      blooming in the future. 

PMID- 24132759
TI  - Study of the dynamics of Microcystis aeruginosa and its cyanophage in East Lake
      using quantitative PCR.

PMID- 24132760
TI  - Valproic acid, valproate and divalproex in the maintenance treatment of bipolar
      disorder.
AB  - BACKGROUND: Bipolar disorder is a recurrent illness that is amongst the top 30
      causes of disability worldwide and is associated with significant healthcare
      costs. In the past, emphasis was placed solely on the treatment of acute episodes
      of bipolar disorder; recently, the importance of episode prevention and of
      minimisation of iatrogenicity has been recognised. For many years, lithium was
      the only mood stabiliser in common use, and it remains an agent of first choice
      in the preventative treatment of bipolar disorder. However, an estimated 20% to
      40% of patients may not respond adequately to lithium. Valproate is an
      anticonvulsant drug that has been shown to be effective in acute mania and is
      frequently used in maintenance treatment of bipolar disorder. When the
      acceptability of long-term treatment is considered, together with efficacy, the
      adverse event profile of a medication is also important. This is an update of a
      Cochrane review first published in 2001 and last updated in 2009. OBJECTIVES: 1.
      To determine the efficacy of valproate continuation and maintenance treatment:a)
      in preventing or attenuating manic, depressive and mixed episodes of bipolar
      disorder;b) in preventing or attenuating episodes of bipolar disorder in patients
      with rapid cycling disorder; and; c) in improving patients' general health and
      social functioning, as measured by global clinical impression, employment and
      marital stability.2. To review the acceptability to patients of long-term
      valproate treatment, as measured by numbers of dropouts and reasons for dropping
      out, by compliance and by reference to patients' expressed views regarding
      treatment.3. To investigate the adverse effects of valproate treatment (including
      general prevalence of side effects) and overall mortality rates. SEARCH METHODS:
      Search of the Cochrane Register of Controlled Trials and the Cochrane Depression,
      Anxiety and Neurosis Group Register (CCDANCTR) (to January 2013), which includes
      relevant randomised controlled trials from the following bibliographic databases:
      The Cochrane Library (all years), EMBASE, (1974 to date), MEDLINE (1950 to date)
      and PsycINFO (1967 to date). No language restrictions were applied. Reference
      lists of relevant papers and previous systematic reviews were handsearched.
      Pharmaceutical companies marketing valproate and experts in this field were
      contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials
      allocating participants with bipolar disorder to long-term treatment with
      valproate or any other mood stabiliser, or antipsychotic drugs, or placebo.
      Maintenance treatment was defined as treatment instituted specifically or mainly
      to prevent further episodes of illness. DATA COLLECTION AND ANALYSIS: Three
      review authors independently extracted data. A double-entry procedure was
      employed by two review authors. Information extracted included study
      characteristics, participant characteristics, intervention details and outcome
      measures in terms of efficacy, acceptability and tolerability. For dichotomous
      data, risk ratios were calculated with 95% confidence intervals (CIs). For
      statistically significant results, we calculated the number needed to treat for
      an additional beneficial outcome (NNTB) and the number needed to treat for an
      additional harmful outcome (NNTH). For continuous data, mean differences (MDs) or
      standardised mean differences (SMDs) were calculated along with 95% CIs. MDs were
      used when the same scale was used to measure an outcome; SMDs were employed when
      different scales were used to measure the same outcome. The primary analysis used
      a fixed-effect model. Binary outcomes were calculated on a strict intention-to
      treat (ITT) basis; dropouts were included in this analysis. When data were
      missing and the method of "last observation carried forward" (LOCF) had been used
      to do an ITT analysis, then the LOCF data were used. MAIN RESULTS: Six randomised
      controlled trials (overall 876 participants) lasting 6 to 24 months were
      included. Two studies (overall 312 participants) compared valproate with placebo,
      four studies (overall 618 participants) valproate with lithium, one study
      (overall 23 participants) valproate with olanzapine and one study (overall 220
      participants) valproate with the combination of valproate plus lithium. In terms
      of study quality, most studies reported the methods used to generate random
      sequence; however, only one study reported enough details on allocation
      concealment. Four of six included studies described their design as "double
      blind", but only two trials reported full details about blinding. Valproate was
      more effective than placebo in preventing study withdrawal due to any mood
      episode (RR 0.68, 95% CI 0.49 to 0.93; NNTB 8), but no difference in efficacy was
      found between valproate and lithium (RR 1.02, 95% CI 0.87 to 1.20). Valproate was
      associated with fewer participants dropping out of treatment for any cause when
      compared with placebo or lithium (RR 0.82, 95% CI 0.71 to 0.95 and RR 0.87, 95%
      CI 0.77 to 0.98, respectively). However, combination therapy with lithium plus
      valproate was more likely to prevent relapse than was monotherapy with valproate
      (RR 0.78, 95% CI 0.63 to 0.96). Significant differences in adverse event
      frequencies were found, and lithium was associated with more frequent diarrhoea,
      polyuria, increased thirst and enuresis, whereas valproate was associated with
      increased sedation and infection. AUTHORS' CONCLUSIONS: Limited evidence supports
      the efficacy of valproate in the long-term treatment of bipolar disorder.
      Clinicians and patients should consider acceptability and tolerability profile
      when choosing between lithium and valproate-their combination or other agents-as
      long-term treatment for bipolar disorder.

PMID- 24132761
TI  - Negative pressure wound therapy for treating foot wounds in people with diabetes
      mellitus.
AB  - BACKGROUND: Foot wounds in people with diabetes mellitus (DM) are a common and
      serious global health issue. Negative pressure wound therapy can be used to treat
      these wounds and a clear and current overview of current evidence is required to
      facilitate decision-making regarding its use. OBJECTIVES: To assess the effects
      of negative pressure wound therapy compared with standard care or other adjuvant
      therapies in the healing of foot wounds in people with DM. SEARCH METHODS: In
      July 2013, we searched the following databases to identify reports of relevant
      randomised controlled trials (RCTs): Cochrane Wounds Group Specialised Register;
      The Cochrane Central Register of Controlled Trials (CENTRAL); The Database of
      Abstracts of Reviews of Effects (DARE); The NHS Economic Evaluation Database;
      Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid
      EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: Published or unpublished RCTs that
      evaluate the effects of any brand of negative pressure wound therapy in the
      treatment of foot wounds in people with diabetes, irrespective of publication
      date or language of publication. Particular effort was made to identify
      unpublished studies. DATA COLLECTION AND ANALYSIS: Two review authors
      independently performed study selection, risk of bias assessment and data
      extraction. MAIN RESULTS: We included five studies in this review randomising 605
      participants. Two studies (total of 502 participants) compared negative pressure
      wound therapy with standard moist wound dressings. The first of these was
      conducted in people with DM and post-amputation wounds and reported that
      significantly more people healed in the negative pressure wound therapy group
      compared with the moist dressing group: (risk ratio 1.44; 95% CI 1.03 to 2.01).
      The second study, conducted in people with debrided foot ulcers, also reported a
      statistically significant increase in the proportion of ulcers healed in the
      negative pressure wound therapy group compared with the moist dressing group:
      (risk ratio 1.49; 95% CI 1.11 to 2.01). However, these studies were noted to be
      at risk of performance bias, so caution is required in their interpretation.
      Findings from the remaining three studies provided limited data, as they were
      small, with limited reporting, as well as being at unclear risk of bias. AUTHORS'
      CONCLUSIONS: There is some evidence to suggest that negative pressure wound
      therapy is more effective in healing post-operative foot wounds and ulcers of the
      foot in people with DM compared with moist wound dressings. However, these
      findings are uncertain due to the possible risk of bias in the original studies.
      The limitations in current RCT evidence suggests that further trials are required
      to reduce uncertainty around decision making regarding the use of NPWT to treat
      foot wounds in people with DM.

PMID- 24132762
TI  - Elevated insulin-like growth factor binding protein-1 (IGFBP-1) in men with
      metastatic prostate cancer starting androgen deprivation therapy (ADT) is
      associated with shorter time to castration resistance and overall survival.
AB  - BACKGROUND: Insulin-like growth factor (IGF) and adipokines have been implicated
      in prostate cancer carcinogenesis. METHOD: Data from 122 men with serum samples
      drawn within 3 months of starting ADT for metastatic prostate cancer was accessed
      retrospectively. IGF-1, IGF binding protein (BP)-1, leptin, and adiponectin
      levels were measured by multiplex electrochemiluminescence assays. A
      multivariable Cox model assessed the association of time to castration resistant
      prostate cancer (CRPC) and overall survival by the protein levels, adjusted for
      clinical variables, age and prostate specific antigen (PSA) levels at start of
      ADT, race, ECOG status, extent of metastases and were reported as hazard ratio
      (HR) with 95% confidence interval (CI). RESULTS: Median follow-up and overall
      survival were 44 and 42.2 months, respectively. ECOG performance status (>= 1 vs.
      0) was negatively associated with overall survival [H  = 2.8 (1.1-7.0), P =
      0.03], and PSA nadir <0.2 was predictive of longer time to CRPC [HR = 0.3 (0.2
      0.5), P < 0.0001]. The median time to CRPC by low, middle, and top IGFBP-1
      tertile distribution was 20.7, 18.1, and 12.4 months, respectively, with HR for
      middle versus low tertile levels 3.1 (1.7-5), P = 0.0003, and for top versus low
      tertile levels was 2.4 (1.3-4.2), P = 0.003. The median overall survival by low,
      middle and top tertile IGFBP-1 level was 48.5, 46.4, and 32.8 months,
      respectively, with HR for top versus low tertile 2.5 (1.2-5.1), P = 0.01. There
      was no association with IGF-1, adiponectin and leptin. CONCLUSION: Elevated IGFBP
      1 appears to be associated with shorter time to CRPC and lower overall survival
      in men with metastatic prostate cancer.

PMID- 24132766
TI  - Comparison of three software systems for semi-automatic volumetry of pulmonary
      nodules on baseline and follow-up CT examinations.
AB  - BACKGROUND: Early diagnosis of lung cancer in a treatable stage is the main
      purpose of lung cancer screening by computed tomography (CT). Accurate three
      dimensional size and growth measurements are essential to assess the risk of
      malignancy. Nodule volumes can be calculated by using semi-automated volumetric
      software. Systematic differences in volume measurements between packages could
      influence nodule categorization and management decisions. PURPOSE: To compare
      volumetric measurements of solid pulmonary nodules on baseline and follow-up CT
      scans as well as the volume doubling time (VDT) for three software packages.
      MATERIAL AND METHODS: From a Lung Cancer Screening study (NELSON), 50
      participants were randomly selected from the baseline round. The study population
      comprised participants with at least one pulmonary nodule at the baseline and
      consecutive CT examination. The volume of each nodule was determined for both
      time points using three semi-automated software packages (P1, P2, and P3). Manual
      modification was performed when automated assessment was visually inaccurate. VDT
      was calculated to evaluate nodule growth. Volume, VDT, and nodule management were
      compared for the three software packages, using P1 as the reference standard.
      RESULTS: In 25 participants, 147 nodules were present on both examinations
      (volume: 12.0-436.6 mm(3)). Initial segmentation at baseline was evaluated to be
      satisfactory in 93.9% of nodules for P1, 84.4 % for P2, and 88.4% for P3.
      Significant difference was found in measured volume between P1 and the other two
      packages (P < 0.001). P2 overestimated the volume by 38 +/- 24%, and P3 by 50 +/-
      22%. At baseline, there was consensus on nodule size categorization in 80% for
      P1&P2 and 74% for P1&P3. At follow-up, consensus on VDT categorization was
      present in 47% for P1&P2 and 44% for P1&P3. CONCLUSION: Software packages for
      lung nodule evaluation yield significant differences in volumetric measurements
      and VDT. This variation affects the classification of lung nodules, especially in
      follow-up examinations.

PMID- 24132763
TI  - Brainstem aminergic nuclei and late-life depressive symptoms.
AB  - IMPORTANCE: The neurobiologic basis of late-life depressive symptoms is not well
      understood. OBJECTIVE: To test the hypothesis that neurodegeneration and neuronal
      density in brainstem aminergic nuclei are related to late-life depressive
      symptoms. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Longitudinal
      clinicopathological cohort study at residences of participants in the Chicago,
      Illinois, metropolitan area. Participants included 124 older persons without
      dementia in the Rush Memory and Aging Project who had annual evaluations for a
      mean (SD) of 5.7 (2.8) years, died, and underwent a postmortem neuropathological
      examination that provided estimates of the densities of Lewy bodies,
      neurofibrillary tangles, and aminergic neurons in the locus ceruleus, dorsal
      raphe nucleus, substantia nigra, and ventral tegmental area. MAIN OUTCOMES AND
      MEASURES: The number of depressive symptoms (mean [SD], 1.61 [1.48]; range, 0-6;
      skewness, 0.94) on the Center for Epidemiological Studies Depression Scale
      averaged across annual evaluations. RESULTS: Brainstem Lewy bodies were
      associated with depressive symptoms, and the association was attenuated in those
      taking antidepressant medication. Brainstem tangles were associated with more
      depressive symptoms in those without cognitive impairment but with fewer symptoms
      in those with mild cognitive impairment. Lower density of tyrosine hydroxylase
      immunoreactive neurons in the ventral tegmental area was robustly associated with
      a higher level of depressive symptoms (mean [SE] estimate, -0.014 [0.003]; P <
      .001; 16.3% increase in adjusted R2). The association was not modified by
      medication use or cognitive impairment. Neither tyrosine hydroxlyase
      immunoreactive neurons in the locus ceruleus nor tryptophan hydroxlyase
      immunoreactive neurons in the dorsal raphe nucleus were related to depressive
      symptoms. CONCLUSIONS AND RELEVANCE: The results suggest that the mesolimbic
      dopamine system, especially the ventral tegmental area, has an important role in
      late-life depressive symptoms.

PMID- 24132767
TI  - Quality of chest radiograph reports.
AB  - BACKGROUND: Examination requests and imaging reports are the most important
      communication instruments between clinicians and radiologists. An accurate and
      clear report helps referring physicians make care decisions for their patients.
      PURPOSE: To evaluate the contents of initial and re-reported chest reports,
      assess the inter-observer agreement, and evaluate the clarity of the report
      contents from the viewpoint of the referring physicians. MATERIAL AND METHODS:
      The content and agreement of the reports were analyzed by comparing the initial
      reports with re-reports prepared by a chest radiologist. The referring physicians
      evaluated the contents of 50 reports regarding their medical facts, clarity, and
      intelligibility. The results were analyzed using cross-over tables, the Pearson
      Chi-Square, and kappa statistics. RESULTS: Radiologists mostly addressed the
      questions posed by the referring physicians. General radiologists included
      separate conclusions in their reports more frequently (22%) than the chest
      radiologist in her re-reports. Reports prepared by the chest radiologist
      contained nearly 50% more findings than the general radiologists' reports. Inter
      observer agreement between the initial and specialist re-reported reports was
      66%, but the kappa value was 0.31. The reports were considered clear/intelligible
      by the referring physicians in 68% of the initial reports by the general
      radiologists and in 94% of the re-reported studies by the chest radiologist.
      CONCLUSION: Radiology report quality was rather high despite their contents
      varying depending on the radiologist. Inter-observer agreement of the chest
      radiographs was low due to the non-structured reports containing different
      quantities of information, thus complicating the comparison. Referring physicians
      considered both short and long radiology reports to be clear.

PMID- 24132768
TI  - Invasive growth patterns of juvenile nasopharyngeal angiofibroma: radiological
      imaging and clinical implications.
AB  - Juvenile nasopharyngeal angiofibroma is a benign lesion with locally aggressive
      nature. Knowledge of its typical growth patterns is crucial for precise
      preoperative staging and adequate preoperative patient counseling. This pictorial
      essay focuses on characteristic radiological features and paths of invasive
      growth of this rare tumor. Also, the impact of accurate preoperative evaluation
      of tumor extensions on surgical planning and results of treatment are discussed. 

PMID- 24132769
TI  - Interventional tumor removal: a new technique for malignant spinal tumor and
      malignant vertebral compression fractures without epidural involvement.
AB  - BACKGROUND: Percutaneous vertebroplasty (PVP) is associated with incomplete pain
      relief and vertebral instability due to cement leakages. PURPOSE: To evaluate the
      feasibility of a new method of PVP, radiofrequency ablation (RFA) and
      interventional tumor removal (ITR) for malignant spinal tumor and malignant
      vertebral compression fractures without epidural involvement. MATERIAL AND
      METHODS: Twelve patients were treated with PVP, RFA, and ITR. A 14 G needle and a
      guidewire were inserted into the vertebral body, followed by sequential
      dilatation of the tract with the working cannula until the last working cannula
      reached the anterior portions of the pedicle. Thereafter, tumors were ablated
      with a radiofrequency probe, and ITR was performed with a marrow nucleus
      rongeurs. Then, cement was injected into the extirpated vertebral body. The data
      were collected and follow-up was performed after 1, 3, and 6 months, and
      thereafter every 6 months postoperatively. RESULTS: PVP, RFA, and ITR were
      technically successful in all patients. The average preoperative pain visual
      analog scale (VAS) score was 7.0 +/- 1.0, which decreased to 2.1 +/- 1.2 at 1
      month, to 1.6 +/- 1.4 at 6 months, to 1.8 +/- 1.7 at 1 year, and was maintained
      at 1.3 +/- 1.1 at >1-year follow-up. A total of 92% patients (11/12) obtained
      excellent and good pain relief with improvement of quality of life. Seven
      patients continued with follow-up healthcare, and five patients died of the
      underlying disease. CONCLUSION: PVP, RFA, and ITR may be a feasible approach for
      malignant spinal tumor and malignant vertebral compression fractures without
      epidural involvement.

PMID- 24132770
TI  - 3.0T MRI tractography of lumbar nerve roots in disc herniation.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) with fiber tracking (FT) has found
      clinical applications in the evaluation of the central nervous system and has
      been extensively used to image white matter tract. The feasibility of FT of the
      lumbar nerve roots in disc herniation is unclear. PURPOSE: To demonstrate the
      feasibility of FT in the lumbar nerve roots, and to assess potential differences
      in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of L4, L5,
      and S1 nerves between healthy disc and disc herniation. MATERIAL AND METHODS:
      Twenty patients with unilateral sciatica related to posterolateral or foraminal
      disc herniation and 20 healthy volunteers were enrolled in our study. Anatomical
      fusion with the axial T2 sequences was used to estimate the relevance of
      reconstructions. DTI with tractography of the L4, L5, and S1 nerves was
      performed. Mean FA and ADC values were calculated from tractography images.
      RESULTS: Lumbosacral root compression sites could be clearly identified on the
      tractography images. There was no significant difference in FA or ADC between
      left and right nerve roots at the same level (P > 0.05) in healthy volunteers.
      The mean FA value of the compressed spinal nerve roots was significantly lower
      than that of FA of the contralateral nerve roots (P = 0.0001). ADC was
      significantly higher in compressed nerve roots than that in the contralateral
      nerve root (P = 0.0002). CONCLUSION: 3 T magnetic resonance imaging (MRI) DTI and
      FT of the lumbosacral region nerve is possible. There are significant changes in
      FA and ADC values in the compressed L4, L5, and S1 nerves.

PMID- 24132771
TI  - The rice nuclear gene WLP1 encoding a chloroplast ribosome L13 protein is needed
      for chloroplast development in rice grown under low temperature conditions.
AB  - Plastidial ribosome proteins (PRPs) form the major component of the plastidial
      ribosome. Here we describe a rice mutant named wlp1 (white leaf and panicles 1)
      selected from a population of tissue culture regenerants. The early seedling
      leaves of the mutant were albino, as was the immature panicle at heading, and the
      phenotype was more strongly expressed in plants exposed to low temperature
      conditions. Changes in the leaf pigmentation of the mutant were due to altered
      chlorophyll content and chloroplast development. Positional cloning of WLP1,
      followed by complementation and knock-down experiments, showed that it encodes a
      50S ribosome L13 protein. The WLP1 protein localized to the chloroplast. WLP1 was
      mainly transcribed in green tissues and particularly abundantly in the early
      seedling leaves. In addition, the expression level of WLP1 was induced by the low
      temperature. The transcription pattern of a number of genes involved in
      plastidial transcription/translation and in photosynthesis was altered in the
      wlp1 mutants. These results reveal that WLP1 is required for normal chloroplast
      development, especially under low temperature conditions. This is the first
      report on the function of PRPs in rice. 

PMID- 24132773
TI  - Pharmacodynamics and pharmacokinetics of a novel, low-dose, soft-gel capsule of
      acetylsalicylic acid in comparison with an oral solution after single-dose
      administration to healthy volunteers: a phase I, two-way crossover study.
AB  - BACKGROUND: Low-dose acetylsalicylic acid (ASA; aspirin) is well-established as a
      platelet anti-aggregating agent for the secondary prevention of cardiovascular
      events. OBJECTIVES: The objective of this study was to investigate the non
      inferiority of a novel ASA 75 mg soft-gel capsule formulation compared with a
      marketed powder for oral solution in terms of reduction in serum thromboxane B2
      (TXB2), a surrogate for platelet aggregation. Pharmacokinetics and tolerability
      of the products were also investigated. METHODS: In this randomised, two-way
      crossover study, 46 male and female healthy subjects received a single dose of
      the investigational products in two periods separated by a 14-day washout. Serum
      TXB2 and plasma ASA were determined up to 24 h post-dose. Maximum percentage of
      TXB2 inhibition (I max) and area under the inhibition-time curve (AUICt) were
      calculated. Non-inferiority was assumed if the lower limits of the 95 %
      confidence intervals (CIs) for the two pharmacodynamic parameters were above 85
      %. RESULTS: The 95 % CI lower limits were 95.35 % for I max and 86.12 % for
      AUICt, i.e. within the pre-specified delta. Time to achieve I max did not differ
      between treatments (p = 0.88). The two formulations were bioequivalent as regards
      the extent of ASA exposure (area under the plasma concentration-time curve from
      zero to time t [AUCt] 90 % CIs 96.67-113.37); a delayed ASA absorption (later
      time to reach maximum plasma concentration [t max], lower maximum plasma
      concentration [C max]) was observed for the test product. No treatment-related
      adverse events were reported. CONCLUSIONS: In healthy subjects, the 75 mg soft
      gel capsules were not inferior to the oral solution in terms of serum TXB2
      inhibition, indicating that the novel formulation could be an effective
      alternative in the secondary prevention of cardiovascular events.

PMID- 24132772
TI  - An open-label drug-drug interaction study of the steady-state pharmacokinetics of
      topiramate and glyburide in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Topiramate is approved for epilepsy and migraine headache management
      and has potential antidiabetic activity. Because topiramate and antidiabetic
      drugs may be co-administered, the potential drug-drug interactions between
      topiramate and glyburide (glibenclamide), a commonly used sulfonylurea
      antidiabetic agent, was evaluated at steady state in patients with type 2
      diabetes mellitus (T2DM). METHODS: This was a single-center, open-label, phase I,
      drug interaction study of topiramate (150 mg/day) and glyburide (5 mg/day alone
      and concomitantly) in patients with T2DM. The study consisted of 14-day
      screening, 48-day open-label treatment, and a 7-day follow-up phase. Serial blood
      and urine were obtained and analyzed by liquid chromatography coupled mass
      spectrometry/mass spectrometry for topiramate, glyburide, and its active
      metabolites M1 (4-trans-hydroxy-glyburide) and M2 (3-cis-hydroxy-glyburide)
      concentrations. Pharmacokinetic parameters were estimated by model-independent
      methods. Changes in fasting plasma glucose from baseline and safety parameters
      were monitored throughout the study. RESULTS: Of 28 enrolled patients, 24
      completed the study. Co-administration of topiramate resulted in a significant (p
      < 0.05) decrease in the glyburide area under the concentration-time curve (25 %)
      and maximum plasma concentration (22 %), and reduction in systemic exposure of M1
      (13 %) and M2 (15 %). Renal clearance of M1 (13 %) and M2 (12 %) increased during
      treatment with topiramate. Steady-state pharmacokinetics of topiramate were
      unaffected by co-administration of glyburide. Co-administration of topiramate and
      glyburide was generally tolerable in patients with T2DM. CONCLUSION: Glyburide
      did not affect the pharmacokinetics of topiramate. Co-administration of
      topiramate decreased systemic exposure of glyburide and its active metabolites;
      combined treatment may require dosing adjustments of glyburide as per clinical
      judgment and glycemic control.

PMID- 24132774
TI  - Heterosexual men's ratings of sexual attractiveness of pubescent girls: Effects
      of labeling the target as under or over the age of sexual consent.
AB  - The study aimed to identify implicit and explicit processes involved in reporting
      the sexual attractiveness of photographs of the same pubescent girls labeled as
      either under or within the age of sexual consent in the UK, women, and men. In
      two studies, 53 and 70 heterosexual men (M age 25.2 and 31.0 years) rated the
      sexual attractiveness of photographs in each category presented via computer
      [seeing target photographs of girls labeled as either under- (14-15 years) or
      within the age of consent (16-17 years)], using a 7-point response box. Ratings
      in Study 1 were in response to a question asking participants to rate how
      sexually attractive the person in each photograph was. In Study 2, participants
      rated how sexually attractive they personally found the target. Response times
      were also recorded. Several findings were replicated in both studies (although
      the strength of findings differed). Mean ratings of the sexual attractiveness of
      the underage girls were lower than those of overage girls and women. In addition,
      correlations revealed significantly longer responding times when "underage" girls
      (and men) were rated as more highly sexually attractive. No such relationship
      emerged with the same girls labeled within the age of consent or women. Overall,
      these data suggest that men find pubescent girls identified as being under the
      age of consent sexually attractive, but inhibit their willingness to report this;
      the greater the attraction, the greater the inhibition.

PMID- 24132775
TI  - Shape differences between the faces of homosexual and heterosexual men.
AB  - Previous studies have shown that homosexual men differ from heterosexual men in
      several somatic traits and lay people accurately attribute sexual orientation
      based on facial images. Thus, we may predict that morphological differences
      between faces of homosexual and heterosexual individuals can cue to sexual
      orientation. The main aim of this study was to test for possible differences in
      facial shape between heterosexual and homosexual men. Further, we tested whether
      self-reported sexual orientation correlated with sexual orientation and
      masculinity-femininity attributed from facial images by independent raters. In
      Study 1, we used geometric morphometrics to test for differences in facial shape
      between homosexual and heterosexual men. The analysis revealed significant shape
      differences in faces of heterosexual and homosexual men. Homosexual men showed
      relatively wider and shorter faces, smaller and shorter noses, and rather massive
      and more rounded jaws, resulting in a mosaic of both feminine and masculine
      features. In Study 2, we tested the accuracy of sexual orientation judgment from
      standardized facial photos which were assessed by 80 independent raters. Binary
      logistic regression showed no effect of attributed sexual orientation on self
      reported sexual orientation. However, homosexual men were rated as more masculine
      than heterosexual men, which may explain the misjudgment of sexual orientation.
      Thus, our results showed that differences in facial morphology of homosexual and
      heterosexual men do not simply mirror variation in femininity, and the
      stereotypic association of feminine looking men as homosexual may confound
      judgments of sexual orientation.

PMID- 24132776
TI  - Comparative reproductive output of androphilic and gynephilic males in samoa.
AB  - Debate exists in the behavioral sciences regarding the extent to which
      androphilic males reproduce compared to their gynephilic counterparts.
      Quantitative data that might speak to this debate are surprisingly rare. Here, we
      compared the reproductive output of 235 transgendered, exclusively androphilic
      Samoan males (known locally as fa'afafine) to that of 447 exclusively gynephilic
      Samoan males. Samoan gynephilic male participants fathered significantly more
      children than fa'afafine participants. In fact, none of the fa'afafine in our
      sample produced offspring. On the basis of this evidence and anecdotal accounts
      in the anthropological literature, we contend that absence of reproductive output
      is a near absolute cross-cultural universal characterizing non-Western,
      transgendered androphilic ("third-gender") males. Models for the evolution of
      male androphilia must account for how genes associated with this sexual
      orientation originated in the past and persisted in populations over time despite
      the fact that the vast majority of androphilic males have no direct reproductive
      success.

PMID- 24132777
TI  - Glans necrosis produced by trauma during masturbation.

PMID- 24132778
TI  - Resonance assignment of the NMR spectra of disordered proteins using a multi
      objective non-dominated sorting genetic algorithm.
AB  - A multi-objective genetic algorithm is introduced to predict the assignment of
      protein solid-state NMR (SSNMR) spectra with partial resonance overlap and
      missing peaks due to broad linewidths, molecular motion, and low sensitivity.
      This non-dominated sorting genetic algorithm II (NSGA-II) aims to identify all
      possible assignments that are consistent with the spectra and to compare the
      relative merit of these assignments. Our approach is modeled after the recently
      introduced Monte-Carlo simulated-annealing (MC/SA) protocol, with the key
      difference that NSGA-II simultaneously optimizes multiple assignment objectives
      instead of searching for possible assignments based on a single composite score.
      The multiple objectives include maximizing the number of consistently assigned
      peaks between multiple spectra ("good connections"), maximizing the number of
      used peaks, minimizing the number of inconsistently assigned peaks between
      spectra ("bad connections"), and minimizing the number of assigned peaks that
      have no matching peaks in the other spectra ("edges"). Using six SSNMR protein
      chemical shift datasets with varying levels of imperfection that was introduced
      by peak deletion, random chemical shift changes, and manual peak picking of
      spectra with moderately broad linewidths, we show that the NSGA-II algorithm
      produces a large number of valid and good assignments rapidly. For high-quality
      chemical shift peak lists, NSGA-II and MC/SA perform similarly well. However,
      when the peak lists contain many missing peaks that are uncorrelated between
      different spectra and have chemical shift deviations between spectra, the
      modified NSGA-II produces a larger number of valid solutions than MC/SA, and is
      more effective at distinguishing good from mediocre assignments by avoiding the
      hazard of suboptimal weighting factors for the various objectives. These two
      advantages, namely diversity and better evaluation, lead to a higher probability
      of predicting the correct assignment for a larger number of residues. On the
      other hand, when there are multiple equally good assignments that are
      significantly different from each other, the modified NSGA-II is less efficient
      than MC/SA in finding all the solutions. This problem is solved by a combined
      NSGA-II/MC algorithm, which appears to have the advantages of both NSGA-II and
      MC/SA. This combination algorithm is robust for the three most difficult chemical
      shift datasets examined here and is expected to give the highest-quality de novo
      assignment of challenging protein NMR spectra.

PMID- 24132779
TI  - Equivalence between Euler angle conventions for the description of tensorial
      interactions in liquid NMR: application to different software programs.
AB  - Long-range orientational restraints derived from alignment or rotational
      diffusion tensors have greatly contributed to the expansion of applications in
      biomolecular NMR. The orientation of the principal axis system of these tensors
      is usually described by the so-called Euler angles. However, no clear consensus
      has emerged concerning the convention of the associated orthogonal rotations. As
      a result, the different programs that derive or predict them have adopted
      different conventions, which make comparison between their results difficult.
      Moreover, the rotation schemes are seldom completely described. Here, we
      summarize the different conventions, determine which ones are adopted by commonly
      used software packages, and establish the formal equivalencies between the
      different calculated Euler angles.

PMID- 24132780
TI  - Lifestyle factors and mortality risk in individuals with diabetes mellitus: are
      the associations different from those in individuals without diabetes?
AB  - AIMS/HYPOTHESIS: Thus far, it is unclear whether lifestyle recommendations for
      people with diabetes should be different from those for the general public. We
      investigated whether the associations between lifestyle factors and mortality
      risk differ between individuals with and without diabetes. METHODS: Within the
      European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was
      formed of 6,384 persons with diabetes and 258,911 EPIC participants without known
      diabetes. Joint Cox proportional hazard regression models of people with and
      without diabetes were built for the following lifestyle factors in relation to
      overall mortality risk: BMI, waist/height ratio, 26 food groups, alcohol
      consumption, leisure-time physical activity, smoking. Likelihood ratio tests for
      heterogeneity assessed statistical differences in regression coefficients.
      RESULTS: Multivariable adjusted mortality risk among individuals with diabetes
      compared with those without was increased, with an HR of 1.62 (95% CI 1.51,
      1.75). Intake of fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil
      was related to a lower mortality risk, and intake of butter and margarine was
      related to an increased mortality risk. These associations were significantly
      different in magnitude from those in diabetes-free individuals, but directions
      were similar. No differences between people with and without diabetes were
      detected for the other lifestyle factors. CONCLUSIONS/INTERPRETATION: Diabetes
      status did not substantially influence the associations between lifestyle and
      mortality risk. People with diabetes may benefit more from a healthy diet, but
      the directions of association were similar. Thus, our study suggests that
      lifestyle advice with respect to mortality for patients with diabetes should not
      differ from recommendations for the general population.

PMID- 24132781
TI  - Differential regulation of mouse pancreatic islet insulin secretion and Smad
      proteins by activin ligands.
AB  - AIMS/HYPOTHESIS: Glucose-stimulated insulin secretion (GSIS) from pancreatic beta
      cells is regulated by paracrine factors, the identity and mechanisms of action of
      which are incompletely understood. Activins are expressed in pancreatic islets
      and have been implicated in the regulation of GSIS. Activins A and B signal
      through a common set of intracellular components, but it is unclear whether they
      display similar or distinct functions in glucose homeostasis. METHODS: We
      examined glucose homeostatic responses in mice lacking activin B and in
      pancreatic islets derived from these mutants. We compared the ability of activins
      A and B to regulate downstream signalling, ATP production and GSIS in islets and
      beta cells. RESULTS: Mice lacking activin B displayed elevated serum insulin
      levels and GSIS. Injection of a soluble activin B antagonist phenocopied these
      changes in wild-type mice. Isolated pancreatic islets from mutant mice showed
      enhanced GSIS, which could be rescued by exogenous activin B. Activin B
      negatively regulated GSIS and ATP production in wild-type islets, while activin A
      displayed the opposite effects. The downstream mediator Smad3 responded
      preferentially to activin B in pancreatic islets and beta cells, while Smad2
      showed a preference for activin A, indicating distinct signalling effects of the
      two activins. In line with this, overexpression of Smad3, but not Smad2,
      decreased GSIS in pancreatic islets. CONCLUSIONS/INTERPRETATION: These results
      reveal a tug-of-war between activin ligands in the regulation of insulin
      secretion by beta cells, and suggest that manipulation of activin signalling
      could be a useful strategy for the control of glucose homeostasis in diabetes and
      metabolic disease.

PMID- 24132782
TI  - Systems biology approach to identify alterations in the stem cell reservoir of
      subcutaneous adipose tissue in a rat model of diabetes: effects on
      differentiation potential and function.
AB  - AIMS/HYPOTHESIS: Autologous progenitor cells represent a promising option for
      regenerative cell-based therapies. Nevertheless, it has been shown that ageing
      and cardiovascular risk factors such as diabetes affect circulating endothelial
      and bone marrow-derived progenitor cells, limiting their therapeutic potential.
      However, their impact on other stem cell populations remains unclear. We
      therefore investigated the effects of diabetes on adipose-derived stem cells
      (ASCs) and whether these effects might limit the therapeutic potential of
      autologous ASCs. METHODS: A systems biology approach was used to analyse the
      expression of genes related to stem cell identification in subcutaneous adipose
      tissue (SAT), the stromal vascular fraction and isolated ASCs from Zucker
      diabetic fatty rats and their non-diabetic controls. An additional model of type
      2 diabetes without obesity was also investigated. Bioinformatic approaches were
      used to investigate the biological significance of these changes. In addition,
      functional studies on cell viability and differentiation potential were
      performed. RESULTS: Widespread downregulation of mesenchymal stem cell markers
      was observed in SAT of diabetic rats. Gene expression and in silico analysis
      revealed a significant effect on molecules involved in the maintenance of
      pluripotency and self-renewal, and on the alteration of main signalling pathways
      important for stem cell maintenance. The viability and differentiation potential
      of ASCs from diabetic rats was impaired in in vitro models and in in vivo
      angiogenesis. CONCLUSIONS/INTERPRETATION: The impact of type 2 diabetes on ASCs
      might compromise the efficiency of spontaneous self-repair and direct autologous
      stem cell therapy.

PMID- 24132783
TI  - Analysis of the gait generation principle by a simulated quadruped model with a
      CPG incorporating vestibular modulation.
AB  - This study aims to understand the principles of gait generation in a quadrupedal
      model. It is difficult to determine the essence of gait generation simply by
      observation of the movement of complicated animals composed of brains, nerves,
      muscles, etc. Therefore, we build a planar quadruped model with simplified
      nervous system and mechanisms, in order to observe its gaits under simulation.
      The model is equipped with a mathematical central pattern generator (CPG),
      consisting of four coupled neural oscillators, basically producing a trot
      pattern. The model also contains sensory feedback to the CPG, measuring the body
      tilt (vestibular modulation). This spontaneously gives rise to an unprogrammed
      lateral walk at low speeds, a transverse gallop while running, in addition to
      trotting at a medium speed. This is because the body oscillation exhibits a
      double peak per leg frequency at low speeds, no peak (little oscillation) at
      medium speeds, and a single peak while running. The body oscillation autonomously
      adjusts the phase differences between the neural oscillators via the feedback. We
      assume that the oscillations of the four legs produced by the CPG and the body
      oscillation varying according to the current speed are synchronized along with
      the varied phase differences to keep balance during locomotion through postural
      adaptation via the vestibular modulation, resulting in each gait. We succeeded in
      determining a single simple principle that accounts for gait transition from
      walking to trotting to galloping, even without brain control, complicated leg
      mechanisms, or a flexible trunk.

PMID- 24132784
TI  - PRDA1, a novel chloroplast nucleoid protein, is required for early chloroplast
      development and is involved in the regulation of plastid gene expression in
      Arabidopsis.
AB  - Chloroplast development requires accurate spatio-temporal expression of plastid
      genes. The regulation of plastid genes mediated by plastid-encoded RNA polymerase
      (PEP) is rather complex, and its related mechanism remains largely unclear. Here,
      we report the identification of a novel protein that is essential for plant
      development, PEP-Related Development Arrested 1 (PRDA1). Knock-out of PRDA1 in
      Arabidopsis (prda1 mutant) caused a seedling-lethal, albino phenotype and
      arrested the development of leaf chloroplasts. Localization analysis showed that
      PRDA1 was specifically targeted to chloroplasts and co-localized with chloroplast
      nucleoids, revealing that PRDA1 is a chloroplast nucleoid-associated protein.
      Gene expression analyses revealed that the PEP-dependent plastid transcript
      levels were greatly reduced in prda1. PRDA1 was co-expressed with most of the PEP
      associated proteins. Protein interaction assays showed that PRDA1 clearly
      interacts with MRL7 and FSD2, both of which have been verified as essential for
      PEP-related chloroplast development. Reactive oxygen species scavenging through
      dimethylthiourea markedly alleviated the cotyledon-albino phenotypes of PRDA1 and
      MRL7 RNA interference seedlings. These results demonstrate that PRDA1 is required
      for early chloroplast development and involved in the regulation of plastid gene
      expression.

PMID- 24132785
TI  - Can patient reported outcomes help identify the optimal outcome in palliative
      surgery?
AB  - BACKGROUND: The purpose of this pilot study was to determine whether an open
      ended questionnaire captures severe symptoms in cancer patients undergoing
      palliative surgical consultation that a structured, validated quality-of-life
      assessment does not capture. METHODS: We prospectively used the Functional
      Assessment of Cancer Therapy-General (FACT-G) and an open-ended questionnaire to
      assess the symptoms of patients with incurable malignancies who underwent
      palliative surgical consultation at our institution between January 2011 and
      September 2012. RESULTS: Of the 69 patients enrolled, the most common indications
      for consultation were bowel obstruction (54%), jaundice (13%), wound problems
      (10%), and gastrointestinal bleeding (7%). Of the severe symptoms patients
      reported, 76% were identified with the FACT-G alone, 22% were identified with the
      open-ended questionnaire alone, and 2% were duplicate responses captured with
      both the FACT-G and open-ended questionnaire. The open-ended questionnaire
      captured 68 instances of severe symptoms in 47 patients that the FACT-G did not
      capture; of these symptoms, 52 were considered to be highly relevant to surgery
      and potential outcome measures. CONCLUSIONS: An open-ended questionnaire can
      identify severe symptoms that a global quality of life survey cannot capture and
      could be used in conjunction with a global survey to reassess symptoms after
      palliative surgical consultation.

PMID- 24132786
TI  - Sleep-related headache and its management.
AB  - OPINION STATEMENT: Sleep and headache have both generated curiosity within the
      human mind for centuries. The relationship between headache and sleep disorders
      is very complex. While Lieving in 1873 first observed that headaches were linked
      to sleep, Dexter and Weitzman in 1970 described the relationship between headache
      and sleep stages. Though our understanding of sleep and headache relationship has
      improved over the years with expanding knowledge in both fields and assessment
      tools such as polysomnography, it is still poorly understood. Headache and sleep
      have an interdependent relationship. Headache may be intrinsically related to
      sleep (migraine with and without aura, cluster headache, hypnic headache, and
      paroxysmal hemicrania), may cause sleep disturbance (chronic migraine, chronic
      tension-type headache, and medication overuse headache) or a manifestation of a
      sleep disorder like obstructive sleep apnea. Headache and sleep disorder may be a
      common manifestation of systemic dysfunction-like anemia and hypoxemia. Headaches
      may occur during sleep, after sleep, and in relation to different sleep stages.
      Lack of sleep and excessive sleep are both considered triggers for migraine.
      Insomnia is more common among chronic headache patients. Experimental data
      suggest that there is a common anatomic and physiologic substrate. There is
      overwhelming evidence that cluster headache and hypnic headaches are
      chronobiological disorders with strong association with sleep and involvement of
      hypothalamus. Cluster headache shows a circadian and circannual rhythmicity while
      hypnic headache shows an alarm clock pattern. There is also a preferential
      occurrence of cluster headache, hypnic headache, and paroxysmal hemicrania during
      REM sleep. Silencing of anti-nociceptive network of periaqueductal grey (PAG),
      locus ceruleus and dorsal raphe nucleus doing REM sleep may explain the
      preferential pattern. Sleep related headaches can be classified into (1)
      headaches with high association with obstructive sleep apnea, which includes
      cluster headache, hypnic headache, and headache related to obstructive sleep
      apnea; and (2) headaches with high prevalence of insomnia, medication overuse,
      and psychiatric comorbidity including chronic migraine and chronic tension-type
      headache. The initial step in the management of sleep related headache is proper
      diagnosis with exclusion of secondary headaches. Screening for sleep disorders
      with the use of proper tests including polysomnography and referral to sleep
      clinic, when appropriate is very helpful. Control of individual episode in less
      than 2 hours should be the initial goal using measures to abort and prevent a
      relapse. Cluster headache responds very well to injectable Imitrex and oxygen.
      Verapamil, steroids and lithium are used for preventive treatment of cluster
      headache. Intractable cluster headache patients have responded to hypothalamic
      deep brain stimulation. Hypnic headache patients respond to nightly caffeine,
      indomethacin, and lithium. Paroxysmal hemicrania responds very well to
      indomethacin. Early morning headaches associated with obstructive sleep apnea
      respond to CPAP or BiPAP with complete resolution of headache within a month.
      Patient education and lifestyle modification play a significant role in overall
      success of the treatment. Chronic tension-type headache and chronic migraine have
      high prevalence of insomnia and comorbid psychiatric disorders, which require
      behavioral insomnia treatment and medication if needed along with psychiatric
      evaluation. Apart from the abortive treatment tailored to the headache types, -
      such as triptans and DHE 45 for migraine and nonsteroidal anti-inflammatory
      medication for chronic tension-type headache, preventive treatment with different
      class of medications including antiepileptics (Topamax and Depakote), calcium
      channel blockers (verapamil), beta blockers (propranolol), antidepressants
      (amitriptyline), and Botox may be used depending upon the comorbid conditions.

PMID- 24132787
TI  - Absolute free energies of biomolecules from unperturbed ensembles.
AB  - Computing the absolute free energy of a macromolecule's structural state, F, is a
      challenging problem of high relevance. This study presents a method that computes
      F using only information from an unperturbed simulation of the macromolecule in
      the relevant conformational state, ensemble, and environment. Absolute free
      energies produced by this method, dubbed Valuation of Local Configuration
      Integral with Dynamics (VALOCIDY), enable comparison of alternative states. For
      example, comparing explicitly solvated and vaporous states of amino acid side
      chain analogs produces solvation free energies in good agreement with
      experiments. Also, comparisons between alternative conformational states of model
      heptapeptides (including the unfolded state) produce free energy differences in
      agreement with data from MUs molecular-dynamics simulations and experimental
      propensities. The potential of using VALOCIDY in computational protein design is
      explored via a small design problem of stabilizing a beta-turn structure. When
      VALOCIDY-based estimation of folding free energy is used as the design metric,
      the resulting sequence folds into the desired structure within the atomistic
      force field used in design. The VALOCIDY-based approach also recognizes the
      distinct status of the native sequence regardless of minor details of the
      starting template structure, in stark contrast with a traditional fixed-backbone
      approach.

PMID- 24132788
TI  - Brain trauma, PET scans and forensic complexity.
AB  - Positron Emission Tomography (PET) is a medical imaging technique that can be
      used to show brain function. Courts have admitted PET scan evidence in cases
      involving brain damage, injury, toxic exposure, or illness ("brain trauma") and
      to support claims of diminished cognitive abilities and impulse control. Despite
      the limited data on the relationships between PET, brain trauma and behavior,
      many courts admit PET scan evidence without much critical analysis. This article
      examines the use of PET as proof of functional impairment and justification of
      abnormal behavior by explaining its diagnostic use and limitations, the limited
      support for claims of its relationship to behavior, and evidentiary
      considerations that should govern its admission into court as evidence. The
      authors urge courts to consider PET evidence, claims of experts, and the scope of
      the proposed testimony with greater deference to the clinical scope of PET, as
      outlined by the American College of Radiology's appropriateness criteria and the
      Working Group Report of the American Psychiatric Association.

PMID- 24132789
TI  - On the link between media coverage of anorexia and pro-anorexic practices on the
      web.
AB  - OBJECTIVE: Links between media portrayals of celebrities and participation in
      activities related to anorexia are of interest to both researchers and
      practitioners but are difficult to study over long time periods and in large
      populations. Here we aim to determine the links between media portrayals of
      celebrities and online practices related to anorexia. METHOD: We examined the
      Internet searching activities of 9.2 million people, focusing on searches related
      to known celebrities, especially those perceived by the public as suffering from
      anorexia, and on searches indicative of anorexic practices. Additionally, we
      tracked media attention of individual celebrities by monitoring all messages from
      Twitter related to those celebrities. RESULTS: We found that a subset of users
      focus their browsing activities on celebrities perceived as anorexic. There was
      an increase of 14% in the hazard of performing anorexia-related searches after
      searching for information on the celebrities most perceived as anorexic. Media
      attention of a celebrity was a trigger for search activity, and when focused on a
      celebrity perceived as anorexic, resulted in a 33% increase in hazard for
      carrying out anorexic searches. Strikingly, when media attention included a
      reference to anorexia, the hazard decreased by 22%. DISCUSSION: Our findings
      suggest that it would be beneficial for media, when reporting on those
      celebrities who are known to suffer from anorexia, to include this information in
      their reporting.

PMID- 24132790
TI  - Sexual dimorphism in relative sacral breadth among catarrhine primates.
AB  - As the sacrum contributes to the size and shape of the birth canal, the sexually
      dimorphic sacrum of humans is frequently interpreted within obstetric contexts.
      However, while the human sacrum has been extensively studied, comparatively
      little is known about sacral morphology in nonhuman primates. Thus, it remains
      unclear whether sacral sexual dimorphism exists in other primates, and whether
      potential dimorphism is primarily related to obstetrics or other factors such as
      body size dimorphism. In this study, sacra of Homo sapiens, Hylobates lar,
      Nasalis larvatus, Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, and Pan
      paniscus were evaluated for sexual dimorphism in relative sacral breadth (i.e.,
      the ratio of overall sacral breadth to first sacral vertebral body breadth). Homo
      sapiens, H. lar, N. larvatus, and G. gorilla exhibit dimorphism in this ratio. Of
      these, the first three species have large cephalopelvic proportions, whereas G.
      gorilla has small cephalopelvic proportions. P. pygmaeus, P. troglodytes, and P.
      paniscus, which all have small cephalopelvic proportions, were not dimorphic for
      relative sacral breadth. We argue that among species with large cephalopelvic
      proportions, wide sacral alae in females facilitate birth by increasing the
      pelvic inlet's transverse diameter. However, given the small cephalopelvic
      proportions among gorillas, an obstetric basis for dimorphism in relative sacral
      breadth appears unlikely. This raises the possibility that sacral dimorphism in
      gorillas is attributable to selection for relatively narrow sacra in males rather
      than relatively broad sacra in females. Accordingly, these results have
      implications for interpreting pelvic dimorphism among fossil primates, including
      hominins.

PMID- 24132791
TI  - Updates on surgical treatments for pediatric scoliosis.
AB  - Scoliosis in children poses serious problems including respiratory problems,
      trunk imbalance, and depression, as well as detracting from the child's
      appearance. Scoliosis can also contribute to back pain later in life. Advanced
      surgical techniques allow for good correction and maintenance of progressive
      curves, and growth-sparing treatments are now available for patients with early
      onset scoliosis (EOS). Posterior corrective surgeries using pedicle screw (PS)
      constructs, which allow curves to be corrected in three dimensions, has become
      the most popular surgical treatment for scoliosis. Several navigation systems and
      probes have been developed to aid in accurate PS placement. For thoracolumbar and
      lumbar curves, anterior surgery remains the method of choice. Growth-sparing
      techniques for treating EOS include growing rods, the Shilla method, anterior
      stapling, and vertical expandable prosthetic titanium rib, which was originally
      designed to treat thoracic insufficiency syndrome. However, these advanced
      surgical techniques do not always offer a perfect solution for pediatric
      scoliosis, and they are associated with complications such as infections and
      problems with instrumentation. Surgeons have developed several techniques in
      efforts to address these complications. We here review historic and recent
      advances in the surgical treatment of scoliosis in children, the problems
      associated with various techniques, and the challenges that remain to be
      overcome. 

PMID- 24132792
TI  - Impact of low back pain, knee pain, and timed up-and-go test on quality of life
      in community-living people.
AB  - BACKGROUND: The Japanese Orthopaedic Association (JOA) has proposed the term
      "locomotive syndrome" (LS) to designate a condition in people from high-risk
      groups with musculoskeletal disease who are highly likely to require nursing care
      at some point. This syndrome is caused by weakening of the musculoskeletal organs
      such as bone, joint, and muscle. The current study investigated factors that
      influence quality of life (QOL) loss caused by LS, which builds upon our previous
      study showing that LS affects individuals' QOL. METHODS: We enrolled 386 subjects
      >50 years old. Sex, age, body mass index and bone mineral density, plus physical
      function tests of grip strength, back muscle strength, maximum stride, 10-m gait
      time, functional reach (cm), timed up-and-go test (TUG) (s) and one-leg standing
      time (s), and the visual analogue scale assessments for leg numbness and knee,
      low back and leg pain were selected as independent variables in a multiple
      regression model for the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the
      Short Form-36 (SF-36), and the Roland Morris Disability Questionnaire (RDQ)
      scores. RESULTS: Low back pain contributed significantly to all JOABPEQ scores.
      Knee pain and TUG contributed significantly to 4/5 and 3/5 of the JOABPEQ scores,
      respectively. Age, TUG, knee pain, and low back pain contributed significantly to
      the RDQ and the physical component summary of the SF-36. CONCLUSIONS: Low back
      and knee pain proved to be significant contributors to individuals' QOL. TUG
      might be the most valuable function test for effectively evaluating an
      individual's QOL.

PMID- 24132793
TI  - Ultrasonographic evaluation of the first extensor compartment of the wrist in de
      Quervain's disease.
AB  - BACKGROUND: This prospective cohort study was undertaken to explore the
      hypothesis that the retinaculum is thicker in de Quervain's disease and to
      identify another landmark for the presence of the intracompartmental septum.
      METHODS: A case group (60 wrists) comprised of Korean female patients with
      unilateral de Quervain's disease and a healthy control group (60 wrists) were
      evaluated by ultrasonography. The case group underwent surgery for extensor
      retinacular release, and surgical findings were used as the reference standard.
      The mean extensor retinacular thickness in the case and control groups was
      compared using a Wilcoxon rank-sum test. A receiver operation characteristic
      curve was constructed for the parameter. RESULTS: The mean thickness of the
      extensor retinaculum was 0.94 mm (SD 0.37) in the case group and 0.35 mm (SD
      0.07) in the control group, and this difference was significant. The cutoff value
      of the extensor retinaculum for diagnosing de Quervain's disease was 0.45 mm
      (sensitivity 96.3%, specificity 93.3%). Bony crests were found in all cases of
      presence of the intracompartmental septum and could be classified into three
      types according to shape. CONCLUSIONS: We concluded that the extensor retinaculum
      is thicker in de Quervain's disease. And the bony crest on the radial styloid can
      be considered a new landmark for determining the presence of an
      intracompartmental septum. TYPE OF STUDY AND LEVEL OF EVIDENCE: Diagnostic, level
      II.

PMID- 24132794
TI  - Female recreational athletes demonstrate different knee biomechanics from male
      counterparts during jumping rope and turning activities.
AB  - BACKGROUND: A variety of athletic exercises are performed in sports training or
      rehabilitation after knee injuries. However, it remains unclear whether males and
      females exhibit similar joint loading during the various athletic motions. The
      purpose of this study was to identify gender differences in knee biomechanics
      during the athletic motions. METHODS: Three-dimensional knee kinematics and
      kinetics were investigated in 20 recreational athletes (10 males and 10 females)
      while jumping rope, backward running, side running, side-to-side running, side-to
      forward running, inside turning, and outside turning. The strengths of the
      quadriceps and hamstring muscles, the knee joint force, the knee joint angle, and
      the knee joint moment were compared between males and females using one-tailed t
      tests. RESULTS: Peak knee anterior force was greater in female recreational
      athletes than in their male counterparts during jumping rope, side-to-forward
      running, inside turning, and outside turning. Female subjects displayed greater
      peak knee abduction angles and greater peak knee flexion moments while jumping
      rope compared to their male counterparts. There were no significant differences
      between the sexes in knee kinematics and kinetics in the frontal and transverse
      planes during running and turning motions. CONCLUSIONS: Female recreational
      athletes exhibited significantly different knee biomechanics compared with male
      counterparts during jumping rope and turning motions.

PMID- 24132795
TI  - A survey of patients who were referred to our palliative care division from other
      hospitals and appeared to have obvious indications for cancer chemotherapies.
AB  - Higashi Sapporo Hospital is a cancer-specific hospital with palliative care
      doctors and certified oncologists. During case conferences held twice a week, we
      routinely evaluate the referred patients. In our case conferences, we selected
      patients who were referred to our palliative care division from other hospitals,
      with possible indications for cancer chemotherapies. We reviewed a total of 1215
      patients who were referred to our palliative care division. We identified 18
      cases as having indications for cancer chemotherapies. Among them, we identified
      4 cases as having indications for standard cancer chemotherapies. All 4 patients
      tolerated the therapies well, responded to chemotherapy, and survived for more
      than 1 year. Conferences in which oncologists and palliative care doctors can
      discuss cases frequently and intimately are thought to be important. 

PMID- 24132796
TI  - Activation of mammalian target of rapamycin contributes to pain nociception
      induced in rats by BmK I, a sodium channel-specific modulator.
AB  - The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of
      the sensitivity of certain adult sensory neurons. Here, we investigated whether
      the mTOR cascade is involved in scorpion envenomation-induced pain
      hypersensitivity in rats. The results showed that intraplantar injection of a
      neurotoxin from Buthus martensii Karsch, BmK I (10 MUg), induced the activation
      of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70
      S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5
      6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h
      and recovered 1 day after injection. Compared with the control group, the ratios
      of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The
      cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed.
      Intrathecal administration of deforolimus, a specific inhibitor of mTOR,
      attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain
      like behavior, and mechanical hypersensitivity). Together, these results imply
      that the mTOR signaling pathway is mobilized by and contributes to experimental
      scorpion sting-induced pain. 

PMID- 24132797
TI  - Antidepressant-like effects and memory enhancement of a herbal formula in mice
      exposed to chronic mild stress.
AB  - Shen Yuan Gan (SYG) is a Chinese herbal prescription composed of total saponins
      of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia (2:1).
      Our previous studies have demonstrated that SYG has antidepressant-like effects
      in various mouse models of behavioral depression. The present study aimed to test
      whether SYG affected chronic mild stress (CMS)-induced depression and cognitive
      impairment in mice. We found that a 5-week CMS schedule induced significant
      degradation of the coat state, decreased sucrose intake in the sucrose-preference
      test, and increased the latency to feed in the noveltysuppressed feeding test.
      All of these CMS-induced changes were ameliorated by SYG (100 and 200 mg/kg) and
      fluoxetine (10 mg/kg). In addition, SYG restored the decreased monoamine
      neurotransmitter concentrations (serotonin, dopamine, norepinephrine and
      acetylcholine) induced by CMS in the prefrontal cortex. Interestingly, SYG
      ameliorated CMS-induced cognitive impairment in the step-through test, and
      increased the acetylcholine level in the prefrontal cortex. These results suggest
      that SYG has an antidepressant-like action and enhances cognition by modulating
      the serotonin, dopamine, norepinephrine, and acetylcholine levels in the
      prefrontal cortex. 

PMID- 24132798
TI  - Synergistic effect of MTHFR C677T and F2 G20210A polymorphisms on ischemic
      stroke.
AB  - The predisposition to stroke might involve interactive effects among variants in
      several genes. We tested this hypothesis by examining the influence of
      polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (C677T) and
      prothrombin (F2) (G20210A) as risk factors for stroke in Morocco. The polymerase
      chain reaction-restriction fragment length polymorphism methods were used to
      analyze DNA from 91 stroke patients and 182 controls. Association between the two
      polymorphisms and the risk of stroke was estimated by four-level models for the
      analysis of genetic interaction. Neither the MTHFR 677TT nor the F2 20210GA
      genotype showed any significant association compared to the MTHFR CC and F2 GG
      genotypes, respectively. An interactive effect between the MTHFR 677TT and F2
      20210GA polymorphisms showed an increased risk of stroke. The odds ratios, in
      univariate and multivariate analysis, for the combined polymorphisms were 4.99
      (95% CI, 1.75-14.2, P = 0.001) and 5.29 (95% CI, 1.63-17.1, P = 0.005),
      respectively. 

PMID- 24132800
TI  - The stapler technique can save lives in trauma patients requiring emergency
      hepatic resection.

PMID- 24132799
TI  - Preventing postoperative recurrence in Crohn's disease: what does the future
      hold?
AB  - Despite an increasing use of immunosuppressants and anti-tumor necrosis factor
      (TNF) agents, approximately half of the patients with Crohn's disease will
      require surgery within 10 years after diagnosis. Postoperative relapse is
      frequent and should be systematically assessed within the first year by
      endoscopy. Absence of prophylactic treatment is associated with a higher risk of
      relapse. Other risk factors include smoking, prior intestinal surgery,
      penetrating disease behavior, perianal location, and extensive small bowel
      resection. Pooled data indicate that 5-aminosalicylic acid and thiopurines have
      only slight efficacy to prevent postoperative recurrence in Crohn's disease.
      Nitroimidazole antibiotics are modestly effective, but long-term toxicity limits
      their use in clinical practice. Recently, anti-TNF agents in this setting have
      demonstrated efficacy and dramatically contrast with other interventions, but
      rising costs are concerning. Anti-TNF agents are highly effective in the
      prevention of postoperative recurrence in these patients. A therapeutic strategy
      based on a risk stratification of patients, with further treatment step-up and
      adjustment if relapse occurs on the basis of ileocolonoscopy, is recommended in
      clinical practice. Should we move towards top-down strategies based on a wider
      use of anti-TNF agents even in patients who are not at high risk of postoperative
      recurrence? Ongoing clinical trials addressing this issue will dramatically
      change our clinical practice.

PMID- 24132801
TI  - Acute cholecystitis: the golden 72-h period is not a strict limit to perform
      early cholecystectomy. Results from 316 consecutive patients.
AB  - PURPOSE: Early laparoscopic cholecystectomy (ELC) is the treatment of choice for
      acute cholecystitis (AC), but the optimal surgical timing is controversial. The
      aim of this study was to retrospectively verify the outcome of patients with AC
      according to different timing of cholecystectomy. METHODS: Patients undergoing
      cholecystectomy for AC from 2006 to 2012 were stratified into two groups: initial
      admission cholecystectomy (IAC) and delayed cholecystectomy (DC, after at least 4
      weeks). Among IAC, a subgroup undergoing immediate cholecystectomy (IC, within 72
      h of symptom onset) was further analyzed. RESULTS: Three-hundred and sixteen
      consecutive patients were studied. IAC group included 262 patients (82.9 %) and
      DC group included 54 patients (17.1 %). The two groups were similar in conversion
      rate, operation length, and overall complication rate. The total length of
      hospitalization was longer in DC patients (p = 0.005). Among DC patients, 25.9 %
      required re-hospitalization while waiting an elective procedure. In the group
      undergoing IC (66 patients), conversion rate, length of operation, and
      postoperative morbidity were similar to that of the IAC group. Length of stay was
      shorter in IC group (p < 0.001). Multivariate analysis identified moderate-severe
      AC grading and ASA score >= 3 as predictors of postoperative complications.
      CONCLUSIONS: The timing of cholecystectomy for AC does not seem to affect
      conversion rate and postoperative morbidity. Therefore the 72-h period should not
      be considered a strict limit to perform LC, provided that the operation is
      carried out during the initial hospital admission.

PMID- 24132802
TI  - Reverse shoulder arthroplasty combined with latissimus dorsi transfer using the
      bone-chip technique.
AB  - PURPOSE: Reverse shoulder arthroplasty (RSA) can restore active elevation in
      rotator-cuff-deficient shoulders. However, RSA cannot restore active external
      rotation. The combination of latissimus dorsi transfer with RSA has been reported
      to restore both active elevation and external rotation. We hypothesised that in
      the combined procedure, harvesting the latissimus dorsi with a small piece of
      bone, leads to good tendon integrity, low rupture rates and good clinical
      outcome. METHODS: Between 2004 and 2010, 13 patients (13 shoulders) were treated
      with RSA in combination with latissimus dorsi transfer in a modified manner. The
      mean follow-up was 65.4 months, and the mean age at index surgery was 71.1 years.
      All patients had external rotation lag sign and positive hornblower's sign, as
      well as radiological signs of cuff-tear arthropathy (Hamada 3, 4 or 5) and fatty
      infiltration grade 3 according to Goutallier et al. on magnetic resonance imaging
      (MRI). The outcome measures included the Constant Murley Score, University of
      California-Los Angeles (UCLA) shoulder score, Simple Shoulder Test (SST), visual
      analogue scale (VAS) and the Activities of Daily Living Requiring External
      Rotation (ADLER) score. Tendon integrity was evaluated with dynamic ultrasound.
      All patients were asked at final follow-up to rate their satisfaction as
      excellent, good, satisfied or dissatisfied. RESULTS: The overall mean Constant
      Murley Shoulder Outcome Score (CMS) improved from 20.4 to 64.3 points (p <
      0.001). Mean VAS pain score decreased from 6.8 to 1.1 (p < 0.001)., mean UCLA
      score improved from 7.9 to 26.4 (p < 0.001), mean SST score improved from 2.3 to
      7.9 (p < 0.001) and mean postoperative ADLER score was 26 points. The average
      degree of abduction improved from 45 degrees  to 129 degrees  (p < 0.001), the
      average degree of anterior flexion improved from 55 degrees  to 138 degrees  (p <
      0.001) and the average degree of external rotation improved from -16 degrees  to
      21 degrees  (p < 0.001). Eight patients rated their results as very satisfied,
      three as satisfied and two as dissatisfied. CONCLUSION: This modified technique,
      which avoids cutting the pectoralis major tendon and involves harvesting the
      tendon together with a small piece of bone, leads to good or even better
      functional results compared with the results reported in the literature, and also
      has high patient satisfaction and low failure rates.

PMID- 24132803
TI  - Anterior cruciate ligament deterioration correlates with patella osteoarthritis.
AB  - PURPOSE: The correlation between anterior cruciate ligament (ACL) condition and
      patella osteoarthritic (OA) changes has not been well reported. The aim of this
      study was to reveal the correlation between ACL deterioration and the morphology
      of OA changes in the patella. The hypothesis was that significant correlation
      between ACL deterioration and patella OA morphology would be revealed in this
      study. METHODS: Two hundred ninety-one cadaveric knees from 151 cadavers were
      included in this study with a median age of 83 years (54-98). Knees were opened
      with a sub-vastus approach and the ACL condition was classified as intact or
      deteriorated. Patella OA lesions were classified using Han's method: type 1, no
      or minimal lesion; type 2, medial facet lesion without involvement of the ridge;
      type 3, lateral facet lesion without involvement of the ridge; type 4, lesion
      involving the ridge only; type 5, medial facet lesion with involvement of the
      ridge; type 6, lateral facet lesion with involvement of the ridge; and type 7,
      global lesion. OA depth evaluation was performed following Outerbridge's
      classification. Statistical analysis of the collected data was performed using
      generalized estimating equations (GEE). RESULTS: The ACL was intact in 277 knees
      and deteriorated in 14 knees. Patella OA lesions were observed as follows: type
      1, 29%; type 2, 15%; type 3, 2%; type 4, 12%; type 5, 18%; type 6, 2%; and type
      7, 22%. Outerbridge's classification of over grade 2 OA depth was observed in
      73.5% of subjects. When patella OA was divided into types 1-4 and types 5-7, ACL
      deterioration was correlated with the occurrence of type 5-7 patella OA [OR 6.44,
      95%CI 2.27-18.25, p = 0.000]. When patella OA was divided into types 1-6 and type
      7, ACL deterioration was correlated with the occurrence of type 7 patella OA [OR
      6.02, 95%CI 2.57-14.09, p = 0.000]. When patella OA depth was divided into grades
      1-3 and grade 4, ACL deterioration was highly correlated with the occurrence of
      grade 4 patella OA [OR 9.31, 95%CI 2.96-29.33, p = 0.025]. CONCLUSION: ACL
      deterioration is a strong risk factor of wider and deeper OA changes in the
      patella. For clinical relevance, subjects with ACL tear should be aware of the
      progression of patella OA.

PMID- 24132804
TI  - Comparison of ambient solvent extraction methods for the analysis of fatty acids
      in non-starch lipids of flour and starch.
AB  - BACKGROUND: Lipids are minor components of flours, but are major determinants of
      baking properties and end-product quality. To the best of our knowledge, there is
      no single solvent system currently known that efficiently extracts all non-starch
      lipids from all flours without the risk of chemical, mechanical or thermal
      damage. This paper compares nine ambient solvent systems (monophasic and
      biphasic) with varying polarities: Bligh and Dyer (BD); modified Bligh and Dyer
      using HCl (BDHCL); modified BD using NaCl (BDNaCl); methanol-chloroform-hexane
      (3:2:1, v/v); Hara and Radin (hexane-isopropanol, 3:2, v/v); water-saturated n
      butanol; chloroform; methanol and hexane for their ability to extract total non
      starch lipids (separated by lipid classes) from wheat flour (Triticum aestivum
      L.). Seven ambient extraction protocols were further compared for their ability
      to extract total non-starch lipids from three alternative samples: barley flour
      (Hordeum vulgare L.), maize starch (Zea mays L.) and tapioca starch (Manihot
      esculenta Crantz). RESULTS: For wheat flour the original BD method and those
      containing HCl or NaCl tended to extract the maximum lipid and a significant
      correlation between lipid extraction yield (especially the glycolipids and
      phospholipids) and the polarity of the solvent was observed. For the wider range
      of samples BD and BD HCl repeatedly offered the maximum extraction yield and
      using pooled standardized (by sample) data from all flours, total non-starch
      lipid extraction yield was positively correlated with solvent polarity (r =
      0.5682, P < 0.05) and water ratio in the solvent mixture (r = 0.5299, P < 0.05).
      CONCLUSION: In general, BD-based methods showed better extraction yields compared
      to methods without the addition of water and, most interestingly, there was much
      greater method dependence of lipid yields in the starches when compared to the
      flour samples, which is due to the differences in lipid profiles between the two
      sample types (flours and starches).

PMID- 24132805
TI  - Beware of "curare cleft" like changes during unilateral capnothorax.
AB  - Capnography is a standard monitoring tool during general anaesthesia.
      Diaphragmatic movement with the weaning of muscle relaxant effect produces the
      characteristic "curare cleft" on capnography. Various artefacts can mimick this
      trace intraoperatively. Cautious interpretation and identification of these is
      essential to avoid any undue overdosing of the patients with muscle relaxants. We
      report "curare cleft" like artefact during ventilation with a single lumen tube
      in a patient with unilateral capnothorax undergoing minimally invasive
      esophagectomy. 

PMID- 24132806
TI  - Inexpensive video-laryngoscopy guided intubation using a personal computer:
      initial experience of a novel technique.
AB  - Video-laryngoscopy may provide an enhanced view of laryngeal structures compared
      to direct visualization. Commercial video-laryngoscopes are often expensive,
      limiting its adoption for routine use. We describe our initial experience using
      an inexpensive custom made device. Patients >15 years age, were randomly chosen,
      after informed consent, for video-laryngoscopy. A custom device easily assembled
      using an USB endoscopic camera, a conventional Macintosh laryngoscope blade size
      3 or 4, and a personal computer was used. Patients with Mallampati class 1-3 were
      chosen. Video-laryngoscopy was recorded and reviewed. Twenty-four patients aged
      16-68 years, of mean weight 58.46 +/- 12.54 (40-86) kg were studied. The glottis
      could be visualized and intubation could be performed in all patients with 22/24
      patients on first attempt. Mean duration of laryngoscopy was 22.17 +/- 12.78 (7
      59) s. Time taken for intubation, was mean of 28.58 +/- 21.01 (9-89) s. Three
      patients with anticipated difficult airways could be intubated on the first
      attempt. Minor blood staining of the airway was seen in the video in two
      patients. Cormack-Lehane laryngoscopy grade visualized was 1 in 9/24, 2 in 15/24
      patients. Percentage of glottic opening score was 62.29 +/- 28.40 (20-100) %.
      Real-time video could be captured in all cases. The custom-made, inexpensive,
      video-laryngoscopy device is safe and reliable for clinical use. Real-time
      visualization and endotracheal intubation were successful in all patients,
      including those with anticipated difficult airway. Further, this device helps in
      archiving the video of intubation.

PMID- 24132807
TI  - The regulation of iron transport.
AB  - Iron is an essential nutrient, but its concentration and distribution in the body
      must be tightly controlled due to its inherent toxicity and insolubility in
      aqueous solution. Living systems have successfully overcome these potential
      limitations by evolving a range of iron binding proteins and transport systems
      that effectively maintain iron in a nontoxic and soluble form for much, if not
      all, of its time within the body. In the circulation, iron is transported to
      target organs bound to the serum iron binding protein transferrin. Individual
      cells modulate their uptake of transferrin-bound iron depending on their iron
      requirements, using both transferrin receptor 1-dependent and independent
      pathways. Once inside the cell, iron can be chaperoned to sites of need or, if in
      excess, stored within ferritin. Iron is released from cells by the iron export
      protein ferroportin1, which requires the ferroxidase activity of ceruloplasmin or
      hephestin to load iron safely onto transferrin. The regulation of iron export is
      controlled predominantly at the systemic level by the master regulator of iron
      homeostasis hepcidin. Hepcidin, in turn, responds to changes in body iron demand,
      making use of a range of regulatory mechanisms that center on the bone
      morphogenetic protein signaling pathway. This review provides an overview of
      recent advances in the field of iron metabolism and outlines the key components
      of the iron transport and regulation systems.

PMID- 24132808
TI  - Dicer1 is crucial for the oocyte maturation of telotrophic ovary in Nilaparvata
      lugens (STAL) (Hemiptera: Geometroidea).
AB  - As a member of the RNase III nucleases family, Dicer1 (Dcr1) protein plays an
      essential role in the production of microRNAs (miRNAs) and oocyte development.
      Here, the full-length cDNA of Nilaparvata lugens Dcr1 (NlDcr1) was firstly cloned
      and analyzed, and then the function of NlDcr1 gene was investigated by RNAi. The
      open reading frame of NlDcr1 cDNA was 6,720 bp in length (GenBank Accession no.
      JX644040), which encoded for a protein of 2,239 amino acids. The NlDcr1
      transcripts were present in all developmental stages and tissues investigated.
      The lowest levels of NlDcr1 expression were found in the first and second instar
      stage, while the highest in 7- and 9 -day-old female adults. The expression
      levels were relatively higher in fat body, ovary, and midgut. After injecting 100
      ng dsRNA of NlDcr1 into female adult, mRNA level of NlDcr1 gene was depleted
      significantly, and 10 kinds of tested miRNAs levels were downregulated in both
      whole body and ovary. The oocytes of females treated with dsNlDcr1 were smaller
      and badly malformed, among which the follicular cell did not develop normally,
      with unclear boundary between cells. These results suggest that NlDcr1 was
      crucial for the regulation of oogenesis in telotrophic ovary.

PMID- 24132810
TI  - Kinetic energy decomposition scheme based on information theory.
AB  - We proposed a novel kinetic energy decomposition analysis based on information
      theory. Since the Hirshfeld partitioning for electron densities can be formulated
      in terms of Kullback-Leibler information deficiency in information theory, a
      similar partitioning for kinetic energy densities was newly proposed. The
      numerical assessments confirm that the current kinetic energy decomposition
      scheme provides reasonable chemical pictures for ionic and covalent molecules,
      and can also estimate atomic energies using a correction with viral ratios.

PMID- 24132811
TI  - Complications and Visual Prognosis in Children with Aniridia.

PMID- 24132809
TI  - Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney
      injury after high-dose methotrexate therapy.
AB  - STUDY OBJECTIVE: Because the incidence rate of renal impairment is 2-10% for
      patients treated with high-dose methotrexate and renal impairment develops in 0
      12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of
      glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to
      inactive metabolites, which allows for nonrenal clearance in patients with
      delayed renal methotrexate elimination. DESIGN: Pooled analysis of efficacy data
      from four multicenter single-arm compassionate-use clinical trials using
      protocols from 1993 to 2007. PATIENTS: Of 476 patients with renal toxicity and
      delayed methotrexate elimination who were treated with intravenous glucarpidase
      for rescue after high-dose methotrexate, 169 patients had at least one
      preglucarpidase (baseline) plasma methotrexate concentration greater than 1
      MUmol/L and one postglucarpidase methotrexate concentration measurement by high
      performance liquid chromatography and were included in the efficacy analysis;
      renal recovery was assessed in 436 patients who had at least one recorded
      preglucarpidase and postglucarpidase serum creatinine concentration measurement.
      MEASUREMENTS AND MAIN RESULTS: Efficacy was defined as rapid and sustained
      clinically important reduction (RSCIR) in plasma methotrexate concentration, with
      a concentration of 1 MUmol/L or lower at all postglucarpidase determinations.
      Median age of efficacy-evaluable patients was 20 years (range 5 weeks-84 years).
      Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia
      (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum
      methotrexate was 11.7 MUmol/L. At the first (median 15 minutes) through the last
      (median 40 hours) postglucarpidase measurement, plasma methotrexate
      concentrations demonstrated consistent 99% median reduction. RSCIR was achieved
      by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment
      greater than or equal to Common Terminology Criteria for Adverse Events grade 2
      recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase
      administration. CONCLUSION: Glucarpidase caused a clinically important 99% or
      greater sustained reduction of serum methotrexate levels and provided noninvasive
      rescue from methotrexate toxicity in renally impaired patients.

PMID- 24132812
TI  - Probing the consequences of antenna modification in cyanobacteria.
AB  - Photosynthetic organisms rely on antenna systems to harvest and deliver energy
      from light to reaction centers. In fluctuating photic environments, regulation of
      light harvesting is critical for a photosynthetic organism's survival. Here, we
      describe the use of a suite of phycobilisome mutants to probe the consequences of
      antenna truncation in the cyanobacterium Synechocystis sp. PCC 6803. Studies
      using transmission electron microscopy (TEM), hyperspectral confocal fluorescence
      microscopy (HCFM), small-angle neutron scattering (SANS), and an optimized
      photobioreactor system have unraveled the adaptive strategies that cells employ
      to compensate for antenna reduction. As the phycobilisome antenna size decreased,
      changes in thylakoid morphology were more severe and physical segregation of the
      two photosystems increased. Repeating distances between thylakoid membranes
      measured by SANS were correlated with TEM data, and corresponded to the degree of
      phycobilisome truncation. Thylakoid membranes were found to have a high degree of
      structural flexibility, and changes in the membrane system upon illumination were
      rapid and reversible. Phycobilisome truncation in Synechocystis 6803 reduced the
      growth rate and lowered biomass accumulation. Together, these results lend a
      dynamic perspective to the intracellular membrane organization in cyanobacteria
      cells and suggest an adaptive mechanism that allows cells to adjust to altered
      light absorption capabilities, while highlighting the cell-wide implications of
      antenna truncation. 

PMID- 24132813
TI  - Prediction of 8-year cardiovascular outcomes in patients with systemic arterial
      hypertension: value of stress (99m)Tc-tetrofosmin myocardial perfusion imaging in
      a high-risk cohort.
AB  - OBJECTIVE: Systemic arterial hypertension is a strong and prevalent
      cardiovascular risk factor. Currently, information on the very long-term
      prognostic value of single-photon emission computed tomography (SPECT) myocardial
      perfusion imaging (MPI) in patients with systemic arterial hypertension is
      lacking. The aim of this study was to assess the value of stress (99m)Tc
      tetrofosmin MPI for the prediction of very long-term outcome in these patients.
      METHODS: The study population consisted of 608 patients with systemic arterial
      hypertension who underwent exercise or dobutamine stress (99m)Tc-tetrofosmin MPI
      for the assessment of known or suspected coronary artery disease. Follow-up was
      successful in 600 (99%) patients. The endpoints were all-cause mortality, cardiac
      death, nonfatal infarction, and coronary revascularization. Kaplan-Meier survival
      cures were constructed and univariate and multivariate analyses were performed to
      identify predictors of very long-term outcome. RESULTS: The mean age of the
      patients was 59 +/- 10 years, and 65% of them were male. MPI findings were normal
      in 301 patients (50%). Myocardial perfusion abnormalities were fixed in 162 (27%)
      and reversible in 137 (23%) patients. During a median 8.1-year follow-up, 241
      (40%) patients died (121 cardiac deaths), 52 (9%) had a nonfatal myocardial
      infarction, and 128 (21%) underwent coronary revascularization. Survival curves
      in patients with a low vs a high summed difference score diverged up to 5 years
      after the test was performed. Multivariate analyses demonstrated that SPECT MPI
      provided incremental prognostic information up to 5 years after the test.
      CONCLUSIONS: Stress (99m)Tc-tetrofosmin MPI provides incremental prognostic
      information for the prediction of cardiovascular outcome in patients with
      systemic arterial hypertension. Patients with normal stress MPI have a
      significantly better prognosis as compared with those with an abnormal study, up
      to 5 years after the test is performed.

PMID- 24132814
TI  - Complete somatostatin-induced insulin suppression combined with heparin loading
      does not significantly suppress myocardial 18F-FDG uptake in patients with
      suspected cardiac sarcoidosis.
AB  - BACKGROUND: Cardiac 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography
      preceded by extended fasting is used to demonstrate active cardiac sarcoidosis.
      However, physiological insulin-dependent myocardial 18F-FDG uptake often obscures
      18F-FDG uptake in sarcoid lesions. We therefore aimed to completely suppress
      physiological myocardial 18F-FDG uptake by pharmaceutically blocking endogenous
      insulin secretion while elevating free fatty acids (FFAs). METHODS AND RESULTS:
      Six patients with suspected cardiac sarcoidosis were studied in a randomized
      cross-over design: (1) 12 hours fasting followed by 2 hours saline infusion
      (SALINE), and (2) 12 hours fasting followed by 2 hour infusions of somatostatin
      (300 MUg/hour) and heparin (70 mIE/kg/minutes) (SOMA). 18F-FDG PET scans were
      performed post-infusion. Glucose, insulin, and FFA levels were measured and left
      ventricle SUV-values were recorded. During the SALINE infusion, insulin, glucose,
      and FFAs remained stable. By design, the SOMA infusions rapidly (<60 minutes)
      suppressed insulin completely, while FFA levels peaked at 1.13 +/- 0.23 mM.
      However, SOMA infusions only suppressed cardiac 18F-FDG uptake insignificantly
      globally [SUVmean (g/mL): 4.0 +/- 3.3 (SALINE) vs 2.4 +/- 1.2 (SOMA), P = .15]
      and regionally. CONCLUSIONS: Complete insulin suppression combined with markedly
      increased circulating FFAs does not completely suppress physiological myocardial
      18F-FDG uptake and thus conveys no extra diagnostic value compared with extended
      fasting.

PMID- 24132815
TI  - Focal retention of Tc-99m sestamibi at central venous catheter tip: a potential
      source of artifact.

PMID- 24132816
TI  - Is regadenoson an appropriate stressor for MPI in patients with left bundle
      branch block or pacemakers?
AB  - BACKGROUND: Patients with LBBB or ventricular pacemaker undergoing MPI are at
      risk for false positive MPI results in the setting of an elevated heart rate (HR)
      with exercise or dobutamine stress. The areas of increased apparent ischemia are
      typically the LAD and septal territories. METHODS: In a subanalysis of the
      ADVANCE MPI 1 and 2 studies, perfusion on an initial adenosine and a second MPI
      study with regadenoson or adenosine was compared by visual and quantitative
      analysis. Among 2,015 patients, 64 had LBBB and 93 had pacemakers. The
      hemodynamic response during the second scan was compared in those with and
      without LBBB and PM. RESULTS: Following regadenoson, peak HR in the LBBB group
      increased by a mean of 25.4 compared to 15.3 bpm following adenosine (P = .0083).
      In the pacemaker group HR was blunted, 11.8 and 8.1 following regadenoson and
      adenosine, respectively (P = .1262). However, the visually assessed summed
      difference score and the quantitatively assessed extent of ischemia for the LAD
      and septal territories and the entire LV did not differ between the initial
      adenosine and subsequent regadenoson scans. CONCLUSIONS: The significant increase
      in HR observed with regadenoson compared to adenosine did not translate into
      greater perfusion defects in the LAD or septal territories in patients undergoing
      regadenoson stress.

PMID- 24132817
TI  - High-frequency fire alters C : N : P stoichiometry in forest litter.
AB  - Fire is a major driver of ecosystem change and can disproportionately affect the
      cycling of different nutrients. Thus, a stoichiometric approach to investigate
      the relationships between nutrient availability and microbial resource use during
      decomposition is likely to provide insight into the effects of fire on ecosystem
      functioning. We conducted a field litter bag experiment to investigate the long
      term impact of repeated fire on the stoichiometry of leaf litter C, N and P
      pools, and nutrient-acquiring enzyme activities during decomposition in a wet
      sclerophyll eucalypt forest in Queensland, Australia. Fire frequency treatments
      have been maintained since 1972, including burning every 2 years (2yrB), burning
      every 4 years (4 yrB) and no burning (NB). C : N ratios in freshly fallen litter
      were 29-42% higher and C : P ratios were 6-25% lower for 2 yrB than NB during
      decomposition, with correspondingly lower 2yrB N : P ratios (27-32) than for NB
      (34-49). Trends in litter soluble and microbial N : P ratios were similar to the
      overall litter N : P ratios across fire treatments. Consistent with these, the
      ratio of activities for N-acquiring to P-acquiring enzymes in litter was higher
      for 2 yrB than NB, whereas 4 yrB was generally intermediate between 2 yrB and NB.
      Decomposition rates of freshly fallen litter were significantly lower for 2 yrB
      (72 +/- 2% mass remaining at the end of experiment) than for 4 yrB (59 +/- 3%)
      and NB (62 +/- 3%), a difference that may be related to effects of N limitation,
      lower moisture content, and/or litter C quality. Results for older mixed-age
      litter were similar to those for freshly fallen litter although treatment
      differences were less pronounced. Overall, these findings show that frequent fire
      (2 yrB) decoupled N and P cycling, as manifested in litter C : N : P
      stoichiometry and in microbial biomass N : P ratio and enzymatic activities.
      Furthermore, these data indicate that fire induced a transient shift to N-limited
      ecosystem conditions during the postfire recovery phase.

PMID- 24132818
TI  - Long-term survival and quality of life after open abdominal aortic aneurysm
      repair.
AB  - BACKGROUND: Open repair of abdominal aortic aneurysm (AAA) generally involves
      postsurgery admission to the intensive care unit (ICU). Few studies have
      evaluated the impact of surgery for either ruptured or nonruptured AAA (with
      postoperative ICU treatment) on long-term survival and quality of life. The
      primary aim of this study was to quantify long-term survival and health-related
      quality of life (HrQpL) of a cohort of patients undergoing open AAA repair after
      hospital discharge. METHODS: Consecutive patients undergoing open elective or
      acute AAA reconstruction with postoperative admission to the ICU and discharged
      alive from the hospital during 2009 were identified. Primary outcome measures
      were 1-year and long-term mortality. The secondary outcome was the HrQoL using
      the EuroQol-6D (EQ-6D) questionnaire at the end of the follow-up period. RESULTS:
      A total of 263 patients were treated and postoperatively discharged alive: 56 had
      a ruptured AAA (rAAA), 35 a symptomatic AAA, and 172 an asymptomatic AAA. The 1
      year mortality after open AAA repair was 8 %. Overall, 39 % of patients died
      within 10 postoperative years (mean 6.0 +/- 2.8 years). Long-term survival of
      patients with a ruptured or symptomatic aneurysm was similar to that of patients
      undergoing elective aneurysm repair. Long-term HrQoL of the total study
      population was worse than that of an age-matched general Dutch population on the
      EQ-us (range 0-1, difference 0.12). This decrease in HrQoL was mainly seen in
      mobility, self-care, usual activities, and cognition. CONCLUSIONS: Ten years
      after open AAA repair, the overall survival rate was 59 %. Long-term survival and
      HrQoL were similar for patients with a repaired ruptured or symptomatic aneurysm
      and those who underwent elective aneurysm repair. There were also no differences
      in patients with infrarenal versus juxtarenal/suprarenal aneurysms. Surviving
      patients had a lower HrQoL than the age-matched general Dutch population,
      especially regarding mobility, self-care, usual activities, and cognition.

PMID- 24132819
TI  - Ultrasound-guided methylene blue dye injection for parathyroid localization in
      the reoperative neck.
AB  - BACKGROUND: The goal of this study was to review a single institution's
      experience using intraoperative ultrasound-guided (ioUSG) methylene blue dye
      injection for the localization and removal of enlarged parathyroid glands in
      patients with primary hyperparathyroidism and a history of previous neck surgery.
      METHODS: We performed a retrospective review of nine consecutive patients who
      underwent reoperative parathyroidectomy using ioUSG methylene blue dye injection.
      RESULTS: All patients had successful resolution of their hyperparathyroidism,
      with at least a 50 % decrease in intraoperative parathyroid hormone level after
      resection. One patient had transient recurrent laryngeal nerve paresis. There
      were no permanent recurrent laryngeal nerve injuries or cases of permanent
      hypoparathyroidism. CONCLUSIONS: Blue dye injection is a safe and effective
      method of localizing diseased parathyroid glands in the reoperative neck.

PMID- 24132820
TI  - The impact of posthepatectomy liver failure on the recurrence of hepatocellular
      carcinoma.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) who underwent
      hepatectomy often developed an intrahepatic recurrence, even though it was a
      curative one. The relationship between surgery-induced liver damage and the
      recurrence of HCC has not been described. This study evaluated whether
      posthepatectomy liver failure, as defined by the International Study Group of
      Liver Surgery, affected the recurrence of HCC. METHODS: We performed a
      retrospective cohort study of 488 patients with HCC who underwent hepatectomy
      between 2004 and 2012 at Kyoto University Hospital. Early posthepatectomy liver
      failure (EPLF) was defined as liver failure occurring between postoperative days
      5 and 10. The patients were divided into an EPLF group and a non-EPLF group.
      Disease-free survival (DFS) was compared between these groups. The influences of
      host-related, surgery-related, and tumor-related factors on patient outcomes were
      evaluated using multivariate analyses. RESULTS: The EPLF group and the non-EPLF
      group contained 153 and 335 patients, respectively. The probability of DFS was
      significantly increased in the non-EPLF group (median: 574 days) compared to the
      EPLF group (median: 348 days) (hazard ratio, HR [95 % confidence interval, CI]
      1.61 [1.29-2.00]). The multivariate analysis revealed that EPLF was an
      independent factor for DFS (HR [95 % CI] 1.43 [1.13-1.81]), besides the factors
      previously described, including fibrosis (1.32 [1.05-1.67]), stage (1.85 [1.34
      2.51]), tumor differentiation (1.46 [1.11-1.89]), and des-gamma
      carboxyprothrombin (1.39 [1.10-1.74]). CONCLUSIONS: EPLF was associated with
      postoperative HCC recurrence. The prevention of EPLF might improve the prognosis
      of patients with HCC.

PMID- 24132821
TI  - Mandatory resection of strangulation marks in small bowel obstruction?
AB  - BACKGROUND: No evidence is available on how to treat intraoperatively detected
      band-shaped strangulation marks of the bowel wall originating from an adhesive
      band or hernia ring. The authors prefer to resect these hazardous strangulation
      marks to avoid secondary small bowel perforation. This retrospective study
      investigated the prevalence of intraoperatively unrecognized ulceration and
      transmural necrosis at the site of the strangulation marks. METHODS: From July
      2003 to July 2011, a total of 31 of 461 patients with acute bowel obstruction
      underwent small bowel resection due to strangulation marks, exclusively. Seven
      patients had two strangulation marks, resulting in 38 strangulation marks to be
      analyzed. RESULTS: From 38 examined strangulation marks, 14 (36.8 %) exhibited
      deep ulceration or transmural necrosis. Four (10.5 %) necrotic lesions had
      already been recognized intraoperatively, while 7 (18.4 %) unsuspicious
      strangulation marks showed deep ulceration and 3 (7.9 %) showed transmural
      necrosis exclusively at final histopathologic examination. The number of
      strangulation marks that needed to be resected for prevention of one missed deep
      ulceration and/or transmural necrosis of the small bowel was 3.4. The presence of
      deep ulceration or transmural necrosis is associated with an obvious decrease in
      bowel diameter caudad to the strangulation mark. No anastomotic leak occurred.
      CONCLUSION: The severity of small bowel damage at the site of band-shaped
      strangulation marks may be underestimated by surgeons. The present series showed
      favorable results with a resection-per-principle policy for these strangulation
      marks. If an obvious decrease of bowel diameter aborally to the strangulation
      mark is present, resection or seromuscular invagination of the later is
      particularly recommended.

PMID- 24132822
TI  - Influence of preoperative chemotherapy on CT volumetric liver regeneration
      following right hemihepatectomy.
AB  - BACKGROUND: An increasing number of patients undergo major liver resection
      following preoperative chemotherapy. Liver regeneration may be impaired in these
      patients, predisposing them to postoperative liver dysfunction. The aim of the
      present study was to evaluate the effects of preoperative chemotherapy on liver
      regeneration after partial liver resection. METHODS: Patients planned to receive
      right hepatectomy either with (group B) or without (group A) prior chemotherapy
      were identified retrospectively from a prospective multi-institutional database
      created in the conduct of a national randomized controlled trial (RCT). Prior
      chemotherapy was neither an inclusion nor an exclusion criterion of the trial.
      Future remnant liver volume (FRLV) was calculated by measuring total functional
      liver volume and resection specimen on preoperative computed tomography (CT)
      scans. Remnant liver volume after 7 days (V RLV7days) was measured on scheduled
      postoperative CT scans. The early regeneration index 7 days after surgery (RI
      early) was calculated as [(V RLV7days - FRLV) / FRLV] * 100 %. Data are expressed
      as median (interquartile range). RESULTS: A total of 72 patients were enrolled:
      45 in group A and 27 in group B. For the whole group, the liver remnant showed a
      58 % (39 %) increase in volume at day 7 (1) day. The RI early was not
      significantly different between groups A and B, 60 % (36 %) and 50 % (43 %),
      respectively (p = 0.47). The RI early was significantly lower in patients who had
      undergone more than six cycles of chemotherapy. CONCLUSIONS: Preoperative
      chemotherapy does not seem to have a negative impact on early liver regeneration
      after partial liver resection.

PMID- 24132823
TI  - The past and present of liver suture.
AB  - Since the first attempts at resecting parts of diseased livers in the late
      nineteenth century, hemorrhage has been the main obstacle for surgeons. One of
      the first hemostasis techniques in liver resection was liver suture. The idea of
      suturing the liver in order to perform resection was proposed by a team of
      Russian and Polish surgeons from Kharkiv University in today's Ukraine. The liver
      suture became widely popular and has been used in various forms throughout the
      surgical world. Further into the twentieth century, it has lost much of its
      popularity; however, over more than 100 years of existence it has seen several
      peaks in interest. Currently, it is still being used by some liver surgeons as it
      is one of the cheapest ways of obtaining a bloodless liver parenchyma
      transection.

PMID- 24132824
TI  - Single-port cholecystectomy and quality of life: reply.

PMID- 24132825
TI  - Stroke volume response to liver graft reperfusion stress in cirrhotic patients.
AB  - INTRODUCTION: In patients with advanced cirrhosis, stressful stimuli may reveal a
      silent reduced cardiac performance. During liver transplantation (LT), graft
      reperfusion strongly stresses the heart and may unmask latent myocardial
      dysfunction. AIM: The objective of this study was to assess heart response to
      acutely increased preload after liver graft reperfusion and correlate this
      response with preoperative data and outcome. METHODS: Preoperative clinical,
      echocardiographic, and hemodynamic data, and patient outcome were retrospectively
      recorded for 235 liver recipients who had no known cardiac disease. Myocardial
      dysfunction was defined as less than 10 % increase of stroke volume after graft
      reperfusion (non-responder). RESULTS: We found 84 (35.7 %) non-responder
      patients. The non-responders showed higher Model for end-stage liver disease
      scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure
      gradient (p = 0.055), and hyperdynamic state than responders. The percentages of
      patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also
      higher among non-responders. Independent predictors of inadequate cardiac
      response in the multivariate analysis were low preoperative systemic vascular
      resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15-4.82; p = 0.027] and
      enlargement of LAD (OR 2.08, 95 % CI 1.49-2.74; p = 0.044). Non-response was
      associated with higher rates of early cardiovascular events [hazard ratio (HR)
      2.84, 95 % CI 1.09-4.22; p = 0.039] and higher length of intensive care unit stay
      (p = 0.038). No differences were found in 1-year survival rates. CONCLUSIONS:
      Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke
      volume response to unclamping of portal vein, is very prevalent. SVRI and LAD
      were independent predictors of inadequate responses. This condition deserves
      special attention since it may aggravate the early postoperative course of LT.

PMID- 24132826
TI  - Surgical outcomes in hepatocellular carcinoma patients with portal vein tumor
      thrombosis.
AB  - BACKGROUND: Different approaches to surgical treatment of portal vein tumor
      thrombosis (PVTT) have been advocated. This study investigated the outcomes of
      different surgical approaches in hepatocellular carcinoma (HCC) patients with
      PVTT. METHODS: We reviewed prospectively collected data for all patients who
      underwent hepatectomy for HCC at our hospital between December 1989 and December
      2010. Patients were excluded from analysis if they had extrahepatic disease, PVTT
      reaching the level of the superior mesenteric vein, or hepatectomy with a
      positive resection margin. The remaining patients were divided into three groups
      for comparison: group 1, with ipsilateral PVTT resected in a hepatectomy; group
      2, with PVTT extending to or beyond the portal vein bifurcation, treated by en
      bloc resection followed by portal vein reconstruction; group 3, with PVTT
      extending to or beyond the portal vein bifurcation, treated by thrombectomy.
      RESULTS: A total of 88 patients, with a median age of 54 years, were included in
      the analysis. Group 2 patients were younger, with a median age of 43.5 years
      versus 57 in group 1 and 49 in group 3 (p = 0.017). Group 1 patients had higher
      preoperative serum alpha-fetoprotein levels, with a median of 8,493 ng/mL versus
      63.25 in group 2 and 355 in group 3 (p = 0.004), and shorter operation time, with
      a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 (p = 0.018). No
      patient had thrombus in the main portal vein. Two (2.8 %) hospital deaths
      occurred in group 1 and one (10 %) in group 2, but none in group 3 (p = 0.440).
      The rates of complication in groups 1, 2, and 3 were 31.9, 50.0, and 71.4 %,
      respectively (p = 0.079). The median overall survival durations were 10.91, 9.4,
      and 8.58 months, respectively (p = 0.962), and the median disease-free survival
      durations were 4.21, 3.78, and 1.51 months, respectively (p = 0.363). The groups
      also had similar patterns of disease recurrence (intrahepatic: 33.8 vs. 28.6 vs.
      40.0 %; extrahepatic: 16.9 vs. 14.3 vs. 0 %; both: 28.2 vs. 42.9 vs. 40.0 %; no
      recurrence: 21.1 vs. 14.3 vs. 20.0 %; p = 0.836). CONCLUSIONS: The three
      approaches have similar outcomes in terms of survival, complication, and
      recurrence. Effective adjuvant treatments need to be developed to counteract the
      high incidence of recurrence.

PMID- 24132827
TI  - Outcome after curative surgery for gastric cancer patients with type 2 diabetes.
AB  - BACKGROUND: Bariatric surgery has been adapted to the management of morbid
      obesity, leading to not only loss of body weight but also improvement of type 2
      diabetes mellitus (DM). The goal of our study was to evaluate the effect of
      gastrectomy in gastric cancer patients with type 2 DM. METHODS: From 1989 to
      2011, a total of 69 gastric cancer patients receiving curative surgery were
      enrolled in this study. They were diagnosed with type 2 DM preoperatively and all
      are alive without tumor recurrence. The clinical characteristics were compared
      between groups with improved or unimproved DM, and groups were also analyzed
      based on the extent of gastrectomy and different reconstruction methods. RESULTS:
      Of the 69 patients, 58 received subtotal gastrectomy and 11 received total
      gastrectomy. The frequency of DM improvement was significantly higher after total
      gastrectomy than subtotal gastrectomy (81.8 vs. 36.2 %; p = 0.007). Patients with
      DM duration of less than 5 years tended to experience DM improvement after
      surgery more frequently than patients with DM duration of more than 5 years (p =
      0.028). Roux-en-Y esophagojejunostomy (R-Ye) led to a higher rate of DM
      improvement than did R-Y gastrojejunostomy (R-Yg), especially in patients with DM
      duration more than 5 years. Among patients receiving duodenal bypass after
      gastrectomy, R-Ye was associated with a higher frequency of DM improvement than R
      Yg and B-II. CONCLUSIONS: The extent of gastrectomy rather than the
      reconstruction method played an important role in DM improvement after curative
      surgery for gastric cancer.

PMID- 24132828
TI  - Prognostic impact of microscopic tumor involved resection margin in advanced
      gastric cancer patients after gastric resection.
AB  - BACKGROUND: The prognosis of patients with positive surgical resection margins is
      dismal in gastric cancer. However, the influence of positive margin itself on
      prognosis is still uncertain, especially in advanced gastric cancer (AGC). The
      aims of the present study were to evaluate the prognostic impact of microscopic
      tumor involved resection margins in stage III-IV AGC after gastric resection in
      comparison with other well-known factors. METHODS: Among 1,536 consecutive
      gastric cancer patients who received intentional curative resection for stage III
      IV AGC between April 2001 and December 2011 at the National Cancer Center, 35
      patients (2.28 %) had positive resection margins on their final histology. A
      comparison of clinicopathologic characteristics, recurrence pattern, overall
      survival (OS), and disease-free survival (DFS) was made between positive margin
      (PM) patients and negative margin (NM) patients. RESULTS: Among the 35 PM
      patients, 15 (42.9 %) had proximal involved margins, 21 (60.0 %) had distal
      involved margins, and one (2.9 %) had both involved margins. Twenty-eight PM
      patients (80.0 %) were stage III, and 7 (20.0 %) were stage IV. Recurrence was
      significantly higher in PM than NM (63.6 % vs. 39.7 %, respectively; p = 0.005).
      The OS and DFS rates were significantly lower in the PM group than in the NM
      group (14.9 vs. 36.3 months, p < 0.001 and 11.6 vs. 27.1 months, p = 0.005,
      respectively). The presence of PM was an independent risk factor for both OS and
      DFS. CONCLUSIONS: The presence of PM is an independent risk factor for OS and
      DFS. Considering the prognostic impact of PM, a sufficient resection margin
      should be ensured when determining the resection line in gastrectomy with
      curative intent. The reoperation to secure clear resection margins should be
      considered as a treatment of choice in the case of PM.

PMID- 24132829
TI  - Firing properties of entorhinal cortex neurons and early alterations in an
      Alzheimer's disease transgenic model.
AB  - The entorhinal cortex (EC) is divided into medial (MEC) and lateral (LEC)
      anatomical areas, and layer II neurons of these two regions project to granule
      cells of the dentate gyrus through the medial and lateral perforant pathways (MPP
      and LPP), respectively. Stellate cells (SCs) represent the main neurons
      constituting the MPP inputs, while fan cells (FCs) represent the main LPP inputs.
      Here, we first characterized the excitability properties of SCs and FCs in adult
      wild-type (WT) mouse brain. Our data indicate that, during sustained
      depolarization, action potentials (APs) generated by SCs exhibit increased fast
      afterhyperpolarization and overshoot, making them able to fire at higher
      frequencies and to exhibit higher spike frequency adaptation (SFA) than FCs.
      Since the EC is one of the earliest brain regions affected during Alzheimer's
      disease (AD) progression, we compared SCs and FCs firing in 4-month-old WT and
      transgenic Tg2576 mice, a well-established AD mouse model. Tg2576-SCs displayed a
      slight increase in firing frequency during mild depolarization but otherwise
      normal excitability properties during higher stimulations. On the contrary,
      Tg2576-FCs exhibited a decreased firing frequency during mild and higher
      depolarizations, as well as an increased SFA. Our data identify the FCs as a
      neuronal population particularly sensitive to early pathological effects of
      chronic accumulation of APP-derived peptides, as it occurs in Tg2576 mice. As FCs
      represent the major input of sensory information to the hippocampus during memory
      acquisition, early alterations in their excitability profile could significantly
      contribute to the onset of cognitive decline in AD. 

PMID- 24132830
TI  - Dental health of young children prenatally exposed to buprenorphine. A concern of
      child neglect?
AB  - PURPOSE: To study the oral health and dental neglect of prenatally buprenorphine
      exposed 3-year-old children. METHODS: The study consisted of 51 children who as
      newborns tested positive for buprenorphine in a urine screen. The control group
      comprised 68 children previously unexposed to narcotics. The dentist examined the
      children and interviewed their guardians. RESULTS: Buprenorphine-exposed children
      exhibited significantly more early childhood caries than did the control group.
      Caries indices, the number of decayed, missing and filled teeth or tooth surfaces
      and decayed teeth were greater in the buprenorphine-exposed children than the
      control children (p = 0.004, p = 0.004, p = 0.001, respectively). In the
      buprenorphine group, more children showed visible plaque (p = 0.003) and fewer
      children were caries-free (p = 0.009) than in the control group. The control
      children's teeth were also brushed more often than the buprenorphine-exposed
      children's teeth (p = 0.001) and the parents were more involved in their
      children's tooth brushing than were those in the buprenorphine-exposed group (p =
      0.035). CONCLUSIONS: More caries and dental neglect were found in buprenorphine
      exposed children than in controls. These findings highlight the importance of
      routine dental appointments, caries screening and preventive care for children in
      substance-abusing families.

PMID- 24132831
TI  - Neuroprotective effects of resveratrol on damages of mouse cortical neurons
      induced by beta-amyloid through activation of SIRT1/Akt1 pathway.
AB  - Resveratrol (3,5,4'-tihydroxy-trans-stilbene), a polyphenolic phytoalexin found
      in the skin and seeds of grapes, has been reported to possess a wide range of
      biological and pharmacological activities including antioxidant, anti
      inflammatory, and antimutagenic effects. The present study intended to explore
      the neuroprotective effects of resveratrol against Abeta25-35 -induced
      neurotoxicity of cultured mouse cortical neurons and the possible mechanisms
      involved. For this purpose, mouse cortical neurons were cultured and exposed to
      30 MUM Abeta25-35 in the absence or presence of resveratrol (5, 10, and 25 MUM).
      In addition, the potential contribution of the SIRT1/Akt1 neuroprotective pathway
      in resveratrol-mediated protection against Abeta25-35 -induced neurotoxicity was
      also investigated. The results showed that resveratrol dose-dependently increased
      cell viability and reduced the number of apoptotic cells as measured by 3-[4,5
      dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, lactate
      dehydrogenase (LDH) activity assay, reactive oxygen species (ROS) activity assay,
      and Hoechst/PI double staining. Further study revealed that resveratrol through
      activation of SIRT1/Akt1 to avert apoptosis. These findings raise the possibility
      that resveratrol may be a potent therapeutic compound against the
      neurodegenerative diseases.

PMID- 24132832
TI  - Change in psychological problems of adolescents with and without visual
      impairment.
AB  - The present study analyzed change in psychological problems of German adolescents
      with and without visual impairment across a 2-year interval. A total of 182
      adolescents with severe visual impairment and 560 sighted adolescents provided
      longitudinal data. At the start of the study, adolescents with visual impairment
      had, on average, elevated scores on all difficulties scales of the Strengths and
      Difficulties Questionnaire (SDQ) (Goodman R, J Child Psychol Psychiat 38:581
      586), 1997 and about 39 % of them scored in the abnormal range of one or more
      scales as compared to 30.5 % of their sighted peers (p < 0.05). However, between
      group differences of emotional and total problems declined over time. While
      adolescents who are blind and those who have low vision had similar levels of
      psychological problems, SDQ scores showed less improvement in adolescents with an
      earlier age at onset of vision loss. In conclusion, a minority of adolescents
      with visual impairment and with early onset of visual impairment in particular,
      may benefit from psychological interventions aimed at preventing and reducing
      psychological problems and increasing the ability to cope with stressors
      associated with vision loss.

PMID- 24132833
TI  - Emotional and behavioral problems in migrant children and adolescents in Europe:
      a systematic review.
AB  - Based on findings of Stevens and Vollebergh [69], who analyzed cross-cultural
      topics, this review considers the current prevalence of emotional and behavioral
      problems of native children and adolescents in comparison with children with a
      migration background in European countries. 36 studies published from 2007 up to
      2013 chosen from a systematic literature research were included and analyzed in
      their perspective design in detail. Previous studies showed great differences in
      their results: Especially in Germany, many studies compare the heterogeneous
      group of immigrant children with native children to analyze an ethnic minority or
      migration process effect. Only a British and Turkish study demonstrates the
      selection effect in migration. Most Dutch or British studies examined different
      ethnic groups, e.g. Turkish, Moroccan, Surinamese, Pakistani, Indian or Black
      migrant children and adolescents. Migrant childhood in Europe could be declared a
      risk in increasing internalizing problem behavior while the prevalent rate in
      externalizing problem behavior was comparable between native and migrant
      children. A migration status itself can often be postulated as a risk factor for
      children's mental condition, in particular migration in first generation.
      Furthermore, several major influence factors in migrant children's mental health
      could be pointed out, such as a low socio-economic status, a Non-European origin,
      an uncertain cultural identity of the parents, maternal harsh parenting or
      inadequate parental occupation, a minority status, the younger age, gender
      effects or a specific culture declaration in diseases. 

PMID- 24132835
TI  - Classification of gait disturbances: distinguishing between continuous and
      episodic changes.
AB  - The increased awareness of the importance of gait and postural control to quality
      of life and functional independence has led many research groups to study the
      pathophysiology, epidemiology, clinical, and therapeutic aspects of these motor
      functions. In recognition of the increased awareness of the significance of this
      topic, the Movement Disorders journal is devoting this entire issue to gait and
      postural control. Leading research groups provide critical reviews of the current
      knowledge and propose future directions for this evolving field. The intensive
      work in this area throughout the world has created an urgent need for a unified
      language. Because gait and postural disturbances are so common, the clinical
      classification should be clear, straightforward, and simple to use. As an
      introduction to this special issue, we propose a new clinically based
      classification scheme that is organized according to the dominant observed
      disturbance, while taking into account the results of a basic neurological exam.
      The proposed classification differentiates between continuous and episodic gait
      disturbances because this subdivision has important ramifications from the
      functional, prognostic, and mechanistic perspectives. We anticipate that research
      into gait and postural control will continue to flourish over the next decade as
      the search for new ways of promoting mobility and independence aims to keep up
      with the exponentially growing population of aging older adults. Hopefully, this
      new classification scheme and the articles focusing on gait and postural control
      in this special issue of the Movement Disorders journal will help to facilitate
      future investigations in this exciting, rapidly growing area.

PMID- 24132836
TI  - Neurophysiology of gait: from the spinal cord to the frontal lobe.
AB  - Locomotion is a purposeful, goal-directed behavior initiated by signals arising
      from either volitional processing in the cerebral cortex or emotional processing
      in the limbic system. Regardless of whether the locomotion initiation is
      volitional or emotional, locomotion is accompanied by automatic controlled
      movement processes, such as the adjustment of postural muscle tone and rhythmic
      limb movements. Sensori-motor integration in the brainstem and the spinal cord
      plays crucial roles in this process. The basic locomotor motor pattern is
      generated by spinal interneuronal networks, termed central pattern generators
      (CPGs). Responding to signals in proprioceptive and skin afferents, the spinal
      interneuronal networks modify the locomotor pattern in cooperation with
      descending signals from the brainstem structures and the cerebral cortex.
      Information processing between the basal ganglia, the cerebellum, and the
      brainstem may enable automatic regulation of muscle tone and rhythmic limb
      movements in the absence of conscious awareness. However, when a locomoting
      subject encounters obstacles, the subject has to intentionally adjust bodily
      alignment to guide limb movements. Such an intentional gait modification requires
      motor programming in the premotor cortices. The motor programs utilize one's
      bodily information, such as the body schema, which is preserved and updated in
      the temporoparietal cortex. The motor programs are transmitted to the brainstem
      by the corticoreticulospinal system, so that one's posture is anticipatorily
      controlled. These processes enable the corticospinal system to generate limb
      trajectory and achieve accurate foot placement. Loops from the motor cortical
      areas to the basal ganglia and the cerebellum can serve this purpose.

PMID- 24132837
TI  - Imaging: What can it tell us about parkinsonian gait?
AB  - Functional neuroimaging has provided new tools to study cerebral gait control in
      Parkinson's disease (PD). First, imaging of blood flow functions has identified a
      supraspinal locomotor network that includes the (frontal) cortex, basal ganglia,
      brainstem tegmentum, and cerebellum. These studies also emphasize the cognitive
      and attentional dependency of gait in PD. Furthermore, gait in PD and related
      syndromes like progressive supranuclear palsy may be associated with dysfunction
      of the indirect, modulatory prefrontal-subthalamic-pedunculopontine loop of
      locomotor control. The direct, stereotyped locomotor loop from the primary motor
      cortex to the spinal cord with rhythmic cerebellar input appears to be preserved
      and may contribute to the unflexible gait pattern in parkinsonian gait. Second,
      neurotransmitter and proteinopathy imaging studies are beginning to unravel novel
      mechanisms of parkinsonian gait and postural disturbances. Dopamine displacement
      imaging studies have shown evidence for a mesofrontal dopaminergic shift from a
      depleted striatum in parkinsonian gait. This may place additional burden on other
      brain systems mediating attention functions to perform previously automatic motor
      tasks. For example, our preliminary cholinergic imaging studies suggest
      significant slowing of gait speed when additional forebrain cholinergic
      denervation occurs in PD. Cholinergic denervation of the pedunculopontine nucleus
      and its thalamic projections have been associated with falls and impaired
      postural control. Deposition of beta-amyloid may represent another non
      dopaminergic correlate of gait disturbance in PD. These findings illustrate the
      emergence of dopamine non-responsive gait problems to reflect the transition from
      a predominantly hypodopaminergic disorder to a multisystem neurodegenerative
      disorder involving non-dopaminergic locomotor network structures and pathologies.

PMID- 24132838
TI  - Dynamic control of posture across locomotor tasks.
AB  - Successful locomotion depends on postural control to establish and maintain
      appropriate postural orientation of body segments relative to one another and to
      the environment and to ensure dynamic stability of the moving body. This article
      provides a framework for considering dynamic postural control, highlighting the
      importance of coordination, consistency, and challenges to postural control posed
      by various locomotor tasks, such as turning and backward walking. The impacts of
      aging and various movement disorders on postural control are discussed broadly in
      an effort to provide a general overview of the field and recommendations for
      assessment of dynamic postural control across different populations in both
      clinical and research settings. Suggestions for future research on dynamic
      postural control during locomotion also are provided and include discussion of
      opportunities afforded by new and developing technologies, the need for long-term
      monitoring of locomotor performance in everyday activities, gaps in our knowledge
      of how targeted intervention approaches modify dynamic postural control, and the
      relative paucity of literature regarding dynamic postural control in movement
      disorder populations other than Parkinson's disease.

PMID- 24132839
TI  - Characterizing freezing of gait in Parkinson's disease: models of an episodic
      phenomenon.
AB  - Freezing of gait (FOG) is a very disabling and common gait disorder in
      Parkinson's disease (PD). The first aim of this article was to provide a
      methodological and critical review of the most common research approach to
      understand FOG, ie, comparing the behavior of freezers with that of non-freezers.
      The review demonstrates that studies often fall short in clearly defining the
      freezer?non-freezer groups and in controlling for disease severity and other
      confounders. These problems complicate data interpretation on FOG. The second aim
      of this article was to summarize the literature on the potential mechanisms
      behind the episodic nature of FOG in the following four models: (1) The threshold
      model assumes that FOG occurs when the accumulation of various motor deficits
      reinforce each other to a point of motor breakdown; (2) the interference model
      proposes that FOG represents an inability to deal with concurrent cognitive,
      limbic, and motor input, causing an interruption of locomotion; (3) the cognitive
      model views FOG as induced by a failure to process response conflict, leading to
      behavioral indecision; and (4) the decoupling model sees FOG as a disconnection
      between preparatory programming and the intended motor response as a result of
      which automatic movement generation gets stuck. These four theoretical premises
      are still incomplete and do not fully explain FOG. The depletion of motor and
      cognitive reserves and an increasingly complex response to levodopa with disease
      progression will also have an impact on the emergence of FOG episodes.

PMID- 24132841
TI  - Moving forward on gait measurement: toward a more refined approach.
AB  - Gait is emerging as a powerful measurement tool in neurodegenerative disorders to
      identify markers of incipient pathology, inform diagnostic algorithms and disease
      progression, and measure the efficacy of interventions. However, it is unclear
      which of the many gait outcomes is most appropriate for each of these purposes.
      In this review, we summarise key topics relating to gait measurement. We draw on
      literature from Parkinson's disease, ageing, and neurodegenerative disease to
      address the issue of variable selection with the goal of moving toward a
      structured approach to measurement. Findings from this review identify a wide
      range of spatiotemporal and dynamic characteristics; however, their suitability
      differs according to the aim of measurement. Gait speed is useful as a global
      characteristic of performance but may not capture the nature of underlying
      pathology. Inconsistent application, reporting, and interpretation of gait
      outcomes currently preclude a prescriptive approach. Conceptual models of gait
      may facilitate a reasoned approach to outcome selection. We also recommend
      harmonisation of protocols, longitudinal cohort studies, and use of novel
      technologies and methods of analysis to provide a complete picture of gait. Gait
      characteristics are "fit for purpose" when selected according to a clear
      rationale and in accordance with their clinimetric properties. Evidence supports
      the use of gait as a biomarker of disease and to complement diagnosis and inform
      disease management. A structured approach to measurement is urgently required to
      fully realise the contribution gait can make to our understanding of
      neurodegenerative disease.

PMID- 24132840
TI  - Cognitive contributions to gait and falls: evidence and implications.
AB  - Dementia and gait impairments often coexist in older adults and patients with
      neurodegenerative disease. Both conditions represent independent risk factors for
      falls. The relationship between cognitive function and gait has recently received
      increasing attention. Gait is no longer considered merely automated motor
      activity but rather an activity that requires executive function and attention as
      well as judgment of external and internal cues. In this review, we intend to: (1)
      summarize and synthesize the experimental, neuropsychological, and neuroimaging
      evidence that supports the role played by cognition in the control of gait; and
      (2) briefly discuss the implications deriving from the interplay between
      cognition and gait. In recent years, the dual task paradigm has been widely used
      as an experimental method to explore the interplay between gait and cognition.
      Several neuropsychological investigations have also demonstrated that walking
      relies on the use of several cognitive domains, including executive-attentional
      function, visuospatial abilities, and even memory resources. A number of
      morphological and functional neuroimaging studies have offered additional
      evidence supporting the relationship between gait and cognitive resources. Based
      on the findings from 3 lines of studies, it appears that a growing body of
      evidence indicates a pivotal role of cognition in gait control and fall
      prevention. The interplay between higher-order neural function and gait has a
      number of clinical implications, ranging from integrated assessment tools to
      possible innovative lines of interventions, including cognitive therapy for falls
      prevention on one hand and walking program for reducing dementia risk on the
      other.

PMID- 24132843
TI  - Clinical syndromes: Parkinsonian gait.
AB  - Disturbances of gait manifest in almost all cases of Parkinson's disease (PD),
      often leading to loss of mobility and increased mortality. In this review a
      clinically oriented approach to gait disorders in different stages of PD is
      presented. In addition, interactions between motor behavior and mental processing
      will be discussed. Analyzing the clinical features of gait can be helpful to
      differentiate PD from atypical forms of parkinsonism. Bedside tests to
      distinguish parkinsonian gait disorders are reviewed. There is still an unmet
      need to effectively treat complex gait disturbances, which are frequently not
      responsive to dopamine replacement medication. We thus present current approaches
      for the management of dopa-refractory gait disorders.

PMID- 24132842
TI  - Objective biomarkers of balance and gait for Parkinson's disease using body-worn
      sensors.
AB  - Balance and gait impairments characterize the progression of Parkinson's disease
      (PD), predict the risk of falling, and are important contributors to reduced
      quality of life. Advances in technology of small, body-worn, inertial sensors
      have made it possible to develop quick, objective measures of balance and gait
      impairments in the clinic for research trials and clinical practice. Objective
      balance and gait metrics may eventually provide useful biomarkers for PD. In
      fact, objective balance and gait measures are already being used as surrogate
      endpoints for demonstrating clinical efficacy of new treatments, in place of
      counting falls from diaries, using stop-watch measures of gait speed, or clinical
      balance rating scales. This review summarizes the types of objective measures
      available from body-worn sensors. The metrics are organized based on the neural
      control system for mobility affected by PD: postural stability in stance,
      postural responses, gait initiation, gait (temporal-spatial lower and upper body
      coordination and dynamic equilibrium), postural transitions, and freezing of
      gait. However, the explosion of metrics derived by wearable sensors during
      prescribed balance and gait tasks, which are abnormal in individuals with PD, do
      not yet qualify as behavioral biomarkers, because many balance and gait
      impairments observed in PD are not specific to the disease, nor have they been
      related to specific pathophysiologic biomarkers. In the future, the most useful
      balance and gait biomarkers for PD will be those that are sensitive and specific
      for early PD and are related to the underlying disease process.

PMID- 24132844
TI  - Higher-level gait disorders: an open frontier.
AB  - The term higher-level gait disorders (HLGD) defines a category of balance and
      gait disorders that are not explained by deficits in strength, tone, sensation,
      or coordination. HLGD are characterized by various combinations of disequilibrium
      and impaired locomotion. A plethora of new imaging techniques are beginning to
      determine the neural circuits that are the basis of these disorders. Although a
      variety of neurodegenerative and other pathologies can produce HLGD, the most
      common cause appears to be microvascular disease that causes white-matter lesions
      and thereby disrupts balance/locomotor circuits.

PMID- 24132845
TI  - Gait ataxia--specific cerebellar influences and their rehabilitation.
AB  - It is well known that the cerebellum is important for movement control and plays
      a critical role in balance and locomotion. As such, one of the most
      characteristic and sensitive signs of cerebellar damage is gait ataxia. However,
      characterizing ataxic gait is no easy task, because gait patterns are highly
      variable. This variability seems to result from the interaction of different
      factors, namely, (1) the primary motor deficits in balance control and multi
      joint coordination and oculomotor dysfunction, (2) the safety strategies used,
      and (3) inaccurate adjustments in patients with loss of balance. In this report,
      we review different approaches to analyzing ataxic gait and studies to identify
      and quantify the different factors contributing to this movement disorder. We
      also discuss the influence of the cerebellum in adaptive locomotor control, the
      interaction between cognitive load and gait in dual-task paradigms, and the
      recent advances in rehabilitation of gait and posture for patients with
      cerebellar degeneration. In the second part, we discuss open questions concerning
      cerebellar mechanisms in multi-joint coordination during different walking
      conditions. Furthermore, we point out potential future directions in motor
      rehabilitation, with the objective of identifying predictors of rehabilitation
      outcome and the development of individualized training programs that potentially
      involve rehabilitation technology.

PMID- 24132846
TI  - Emerging therapies for gait disability and balance impairment: promises and
      pitfalls.
AB  - Therapeutic management of gait and balance impairment during aging and
      neurodegeneration has long been a neglected topic. This has changed considerably
      during recent years, for several reasons: (1) an increasing recognition that gait
      and balance deficits are among the most relevant determinants of an impaired
      quality of life and increased mortality for affected individuals; (2) the arrival
      of new technology, which has allowed for new insights into the anatomy and
      functional (dis)integrity of gait and balance circuits; and (3) based in part on
      these improved insights, the development of new, more specific treatment
      strategies in the field of pharmacotherapy, deep brain surgery, and
      physiotherapy. The initial experience with these emerging treatments is
      encouraging, although much work remains to be done. The objective of this
      narrative review is to discuss several promising developments in the field of
      gait and balance treatment. We also address several pitfalls that can potentially
      hinder a fast and efficient continuation of this vital progress. Important issues
      that should be considered in future research include a clear differentiation
      between gait and balance as two distinctive targets for treatment and recognition
      of compensatory mechanisms as a separate target for therapeutic intervention.

PMID- 24132847
TI  - Effects of exercise on mobility in people with Parkinson's disease.
AB  - Parkinson's disease is a prevalent neurodegenerative disorder for which only
      symptomatic treatment exists. Gait and balance disturbance is common in
      Parkinson's disease and is a major contributor to increased disability and
      decreased health-related quality of life and survival. Balance and gait deficits
      in Parkinson's disease are notoriously difficult to treat and are not
      significantly helped by pharmacological or surgical treatment. The last two
      decades have seen a dramatic increase in the research and clinical interest in
      using exercise as a treatment for mobility problems in people with Parkinson's
      disease. With exciting advances in basic science research suggesting
      neurochemical and neuroplastic changes after exercise, an increasing number of
      high-quality studies are documenting particular aspects of mobility improving
      after exercise. Exercise has the potential to help both motor (gait, balance,
      strength) and nonmotor (depression, apathy, fatigue, constipation) aspects of
      Parkinson's disease as well as secondary complications of immobility
      (cardiovascular, osteoporosis). This perspective article focuses primarily on
      recent evidence on the effects of exercise in improving mobility while
      highlighting the importance of targeted exercise intervention for maximizing the
      benefits of exercise. Suggestions for exercise guidelines, adherence issues, and
      directions for future research are provided.

PMID- 24132848
TI  - Virtual reality and motor imagery: promising tools for assessment and therapy in
      Parkinson's disease.
AB  - Motor imagery (MI) and virtual reality (VR) are two evolving therapeutic
      approaches that make use of cognitive function to study and enhance movement, in
      particular, balance and mobility of people with Parkinson's disease (PD). This
      review examines the literature on the use of VR and MI in the assessment of
      mobility and as a therapeutic intervention to improve balance and gait in
      patients with PD. A study was eligible for inclusion if MI or VR were used to
      assess motor or cognitive function to improve gait, balance, or mobility in
      patients with PD. Data were extracted on the following categories: participants;
      study design; intervention (type, duration, and frequency); and outcomes.
      Intervention studies were evaluated for quality using the Physiotherapy Evidence
      Database scale. Sixteen studies were identified; 4 articles used MI and 12 used
      VR for assessment and treatment of gait impairments in PD. The studies included
      small samples and were diverse in terms of methodology. Quality of the
      intervention trials varied from fair for VR to good for MI. The benefits of using
      MI and VR for assessment and treatment were noted. Encouraging findings on the
      potential benefits of using MI and VR in PD were found, although further good
      quality research is still needed. Questions remain on the optimal use, content of
      interventions, and generalizability of findings across the different stages of
      the disease. The possible mechanisms underlying MI and VR and recommendations for
      future research and therapy are also presented.

PMID- 24132849
TI  - Deep brain stimulation for gait and postural symptoms in Parkinson's disease.
AB  - In patients with Parkinson's disease, gait and balance difficulties have emerged
      as some of the main therapeutic concerns. During earlier stages of the disease,
      the dopamine-responsive aspects of gait disorder can be treated initially with
      dopaminergic drugs or deep brain stimulation. However, certain temporal aspects
      of parkinsonian gait disorder remain therapeutically resistant in both the short
      term and the long term. In this review, we summarize the effects of deep brain
      stimulation on gait and postural symptoms in the five currently available targets
      (subthalamic nucleus, globus pallidus, ventralis intermedius thalamic nucleus,
      pedunculopontine nucleus, and substantia nigra) and describe programming
      strategies for patients who are mainly disabled by gait problems.

PMID- 24132852
TI  - The frailty phenotype and the frailty index: different instruments for different
      purposes.
AB  - The integration of frailty measures in clinical practice is crucial for the
      development of interventions against disabling conditions in older persons. The
      frailty phenotype (proposed and validated by Fried and colleagues in the
      Cardiovascular Health Study) and the Frailty Index (proposed and validated by
      Rockwood and colleagues in the Canadian Study of Health and Aging) represent the
      most known operational definitions of frailty in older persons. Unfortunately,
      they are often wrongly considered as alternatives and/or substitutables. These
      two instruments are indeed very different and should rather be considered as
      complementary. In the present paper, we discuss about the designs and rationals
      of the two instruments, proposing the correct ways for having them implemented in
      the clinical setting. 

PMID- 24132853
TI  - Specialty experience in geriatric medicine is associated with a small increase in
      knowledge of delirium.
AB  - BACKGROUND: delirium is underdiagnosed and undertreated. Understanding of
      delirium among doctors in medical and ICU settings has previously been shown to
      be low. We hypothesised that junior doctors who had gained experience in
      geriatrics, neurology or psychiatry may have an increased knowledge of delirium.
      METHODS: we used data from a large multi-centre study of junior doctors conducted
      between December 2006 and January 2007 which is, to date, the largest survey of
      understanding of delirium among junior doctors. The original survey used a
      questionnaire within which certain key items led to a correct or incorrect
      answer. Total correct answers were recorded giving a maximum total knowledge
      score of 17 for each participant. The relationship between total knowledge score
      achieved on the questionnaire and time since qualification; specialty experience
      in geriatric medicine, psychiatry and/or neurology and self-reported experience
      with the Confusion Assessment Method (independent variables) were modelled using
      linear regression. RESULTS: around half (53.2%; 399 of 750) of those surveyed
      stated that they had experience in geriatric medicine. In contrast only 4.1 and
      8.0% of respondents had experience in psychiatry and neurology, respectively.
      Experience in geriatric medicine was significantly associated with a modest
      increase in correct answers (4.7 versus 4.3 points, P = 0.020). No other
      variables were significantly associated with better scores. CONCLUSION:
      experience in geriatric medicine leads to a small improvement in understanding of
      delirium among junior doctors.

PMID- 24132854
TI  - Screening for depression in Parkinson's disease: the performance of two screening
      questions.
AB  - BACKGROUND: the study objective was to evaluate the validity of the two questions
      recommended by the UK. National Institute for Health and Clinical Excellence for
      depression screening in Parkinson's disease (PD). METHODS: one hundred and twenty
      patients attending a PD out-patient clinic were interviewed in a standardised
      manner using relevant sections of the Present State Examination- Schedules for
      Clinical Assessment in Neuropsychiatry to identify depression according to
      Diagnostic and Statistical Manual (4th edition) criteria. Participants then
      completed the two depression screening questions and the 15-item Geriatric
      Depression Scale (GDS-15). RESULTS: sensitivity, specificity, positive and
      negative predictive values of the two questions and GDS-15 for major and minor
      depression combined were calculated for different cut-off scores and a receiver
      operating characteristics (ROC) analysis was conducted. A threshold of one or
      more positive responses to the two screening questions gave a sensitivity of 100%
      and specificity of 84% (positive predictive value 54%, negative predictive value
      100%). The area under the ROC curve was 0.95. The optimal cut-off for the GDS-15
      was 5/6, which gave a sensitivity of 84% and specificity of 89% (positive
      predictive value 59%, negative predictive value 97%), and the area under the
      curve was 0.92. CONCLUSION: this study shows that the two depression screening
      questions can be used as an initial screen for depression in patients with PD who
      have no significant cognitive impairment. A positive response to either of the
      questions would indicate that further diagnostic assessment may be warranted.

PMID- 24132855
TI  - The provision of care for residents dying in U.K. nursing care homes.
AB  - OBJECTIVES: to identify the care currently provided to residents dying in U.K.
      nursing care homes. METHOD: study participants were residents who had died within
      38 nursing care homes in southeast England over a 3-year period. The nursing care
      homes had been recruited to take part in a cluster randomised controlled trial
      looking at different models of facilitation while implementing the Gold Standards
      Framework in Care Homes (GSFCH) programme. Two researchers examined the notes and
      daily records of all residents who died in each of these homes between the 1 June
      2008 and the 31 May 2011. RESULTS: a total of 2,444 residents died during the 3
      year period. Fifty-six percent of these residents died within a year of
      admission. The support from specialist healthcare services to residents during
      their last 6 months of life was variable. CONCLUSIONS: nursing care homes have
      established links with some external healthcare providers. These links included
      the GP, palliative care nurses and physiotherapy. As dependency of resident
      increase with 56% residents dying within a year of admission these links need to
      be expanded. The provision of health care that meets the needs of future nursing
      care home residents needs to be 'proactively' obtained rather than left to
      chance.

PMID- 24132856
TI  - Link between oxidative stress and acute brain ischemia.
AB  - The pathogenesis of acute brain ischemia (ABI) is highly complex and involves
      multiple mechanisms including free radical generation. Imbalance between the
      cellular production of free radicals and the ability of cells to defend against
      them is referred to as oxidative stress. Oxidative stress is one of the
      mechanisms contributing to neuronal damage, potentially induced through the ABI.
      Through interactions with a large number of molecules, reactive oxygen species
      may irreversibly destroy or alter the function of the cellular lipids, proteins,
      and nucleic acids and initiate cell signaling pathways after cerebral ischemia.
      Future investigations should focus on the understanding of oxidative stress
      mechanisms and neuroprotection in order to discover new treatment targets. 

PMID- 24132858
TI  - Simulation of in-vivo-equivalent epithelial barriers using a micro fluidic
      device.
AB  - In biomedical approaches cell culture models do often not fully represent their
      biological counterparts. Often the methods used do not completely mimic the in
      vivo situation, either by using only single-cell-type culture approaches, or by
      using inadequate culture conditions. We therefore developed a variable system
      based on individual modules to simulate in vitro equivalent cell-barriers (e.g.
      for mucous layers). This system allows the growth of different communicating cell
      types in micro channels. Hot embossing is used to fabricate the micro structured
      polymer sheets. The stamp for hot embossing is fabricated by UV
      lithography/electroforming or by micro milling. The system consists of a
      container with micro fluidic modules and a pump-system for a continuous medium
      supply. An individual module is made of two micro-structured polycarbonate-sheets
      separated by a transmissible polycarbonate membrane. The two sheets are arranged
      orthogonally to induce a cross flow. The system is highly variable by channel
      geometry (height and width), capacity (number of micro fluidic modules), and pore
      sizes of the transmissible membranes. In a first approach we simulated the
      intestinal mucosa. Epithelial cells and primary neurons of the enteric nervous
      system were cultured on both sides of the transmissible membrane within the two
      different compartments. So the cells could be supplied with two different media.
      We kept a mono-culture of primary neurons or epithelial cells for 5 days and a co
      culture between these two cell-types was established for 4 days. The proposed
      system delivers a sophisticated model for the simulation of various epithelial
      layers which takes the specific biological properties into account. 

PMID- 24132857
TI  - System architecture for a magnetically guided endovascular microcatheter.
AB  - Magnetic resonance imaging (MRI) guided minimally invasive interventions are an
      emerging technology. We developed a microcatheter that utilizes micro
      electromagnets manufactured on the distal tip, in combination with the magnetic
      field of a MRI scanner, to perform microcatheter steering during endovascular
      surgery. The aim of this study was to evaluate a user control system for
      operating, steering and monitoring this magnetically guided microcatheter. The
      magnetically-assisted remote control (MARC) microcatheter was magnetically
      steered within a phantom in the bore of a 1.5 T MRI scanner. Controls mounted in
      an interventional MRI suite, along with a graphical user interface at the MRI
      console, were developed with communication enabled via MRI compatible hardware
      modules. Microcatheter tip deflection measurements were performed by evaluating
      MRI steady-state free precession (SSFP) images and compared to models derived
      from magnetic moment interactions and composite beam mechanics. The magnitude and
      direction of microcatheter deflections were controlled with user hand, foot, and
      software controls. Data from two different techniques for measuring the
      microcatheter tip location within a 1.5 T MRI scanner showed correlation of
      magnetic deflections to our model (R(2): 0.88) with a region of linear response
      (R(2): 0.98). Image processing tools were successful in autolocating the in vivo
      microcatheter tip within MRI SSFP images. Our system showed good correlation to
      response curves and introduced low amounts of MRI noise artifact. The center of
      the artifact created by the energized microcatheter solenoid was a reliable
      marker for determining the degree of microcatheter deflection and auto-locating
      the in vivo microcatheter tip.

PMID- 24132859
TI  - Hominoid humeral morphology: 3D morphometric analysis.
AB  - Variation in humeral morphology among hominoids has long been recognized in
      relation to both phylogeny and behavior. Here, we use 3D landmark data to analyze
      humeral shape among hominoids, including hylobatids (n = 37), Pongo (n = 33),
      Homo (n = 74), Pan (n = 55), and Gorilla (n = 45) to examine the relative
      influence of phylogenetic history vs. locomotor adaptation on humeral shape.
      Principal components analysis (PCA) of Procrustes shape data derived from 19
      humeral type II or type III landmarks (Bookstein, 1991) for these taxa reveals
      the following: PC1, which primarily reflects the humeral torsion (or lack
      thereof) and relative diaphyseal and epiphyseal breadths, separates the
      relatively narrow-shafted, small articular dimensions and low humeral torsion
      Hylobates, and to a lesser extent, Pongo, humeri from those of the African
      hominoids. PC2, which largely contrasts shafts that are posteriorly convex (high
      PC2 scores) with antero-posteriorly straight humeral shafts (low PC2 scores)
      separates Homo, who tend to have A-P straighter shafts, from the more A-P bowed
      humeral shafts of the apes. These shape patterns suggest that the bowed shafts of
      Pan, Pongo, and Gorilla (and to a lesser extent, hylobatids) are due to the fact
      that in each of these taxa, the humerus is a weight-bearing bone, whereas the
      shafts of Homo are freed from locomotion. More subtle behavioral indicators are
      also elucidated, whereas cluster analyses (minimum spanning tree fit to a
      principal coordinates [PCO] plot and UPGMA dendrogram) reveal strong phylogenetic
      signals in the hominoid humerus as well.

PMID- 24132860
TI  - Mercuric reductase activity of multiple heavy metal-resistant Lysinibacillus
      sphaericus G1.
AB  - A culture was isolated from an industrial mercuric salt-contaminated soil, which
      could tolerate Cd, Co, Zn, Cr, and Hg up to 190, 525, 350, 935, and 370 MUM,
      respectively. The isolate was identified as Lysinibacillus sphaericus by 16S rRNA
      gene sequencing. It bioaccumulated Cd, Co, and Zn, and reductively detoxified Cr
      and Hg. Chromate reductase and mercuric reductase (MerA) activities in the cell
      extract were 2.4 and 0.13 units mg(-1) protein, respectively. The study also
      describes designing of broad-specificity primers based on firmicute merA genes.
      These primers were successfully used to amplify a 440 bp merA fragment from the
      current isolate. Based on the partial sequence, complete merA ORF of 1641 bp was
      amplified. It showed 99% similarity to a putative merA gene from distantly
      related Streptococcus agalactiae, but only 72% identity with the well
      characterized merA from a more closely related Bacillus cereus RC607. The gene
      sequence possessed all the features required for the functioning of MerA enzyme,
      and its function was confirmed by recombinant expression in E. coli. To the best
      of our knowledge, this is the first report of full length merA gene from L.
      sphaericus.

PMID- 24132865
TI  - Bonding and reactivity of a MU-hydrido dicopper cation.
AB  - A bent dicopper-hydride cation that has an N-heterocyclic carbene supporting
      ligand has a Cu-H-Cu angle of 122 degrees  in the solid state. Density functional
      theory suggests an open three-centered metal-hydrogen interaction. The hydride
      reacts readily with methanol and with carbon dioxide; insertion of
      phenylacetylene affords a gem-dicopper vinyl complex. 

PMID- 24132866
TI  - Abrupt fire regime change may cause landscape-wide loss of mature obligate seeder
      forests.
AB  - Obligate seeder trees requiring high-severity fires to regenerate may be
      vulnerable to population collapse if fire frequency increases abruptly. We tested
      this proposition using a long-lived obligate seeding forest tree, alpine ash
      (Eucalyptus delegatensis), in the Australian Alps. Since 2002, 85% of the Alps
      bioregion has been burnt by several very large fires, tracking the regional trend
      of more frequent extreme fire weather. High-severity fires removed 25% of
      aboveground tree biomass, and switched fuel arrays from low loads of herbaceous
      and litter fuels to high loads of flammable shrubs and juvenile trees, priming
      regenerating stands for subsequent fires. Single high-severity fires caused adult
      mortality and triggered mass regeneration, but a second fire in quick succession
      killed 97% of the regenerating alpine ash. Our results indicate that without
      interventions to reduce fire severity, interactions between flammability of
      regenerating stands and increased extreme fire weather will eliminate much of the
      remaining mature alpine ash forest. 

PMID- 24132867
TI  - A randomized controlled multicenter trial on the multimodal treatment of adult
      attention-deficit hyperactivity disorder: enrollment and characteristics of the
      study sample.
AB  - Adult ADHD is a frequent psychiatric disorder affecting relevant aspects of an
      individual's life. The aim of our study group was to carry out the first
      randomized controlled multicenter study to evaluate the effects of psychotherapy
      compared to clinical management in combination with psychopharmacological
      treatment with methylphenidate (MPH) or placebo (Plac) in a factorial four-arm
      design. Here, we present the enrollment procedure and description of adult ADHD
      patients recruited for the trial. Four hundred and thirty-three adult patients
      with ADHD were randomized at seven study sites in Germany to four treatment
      conditions: manualized dialectical-behavioral-therapy-based group psychotherapy
      (GPT) plus MPH or Plac, or clinical management (CM) including supportive
      counseling plus MPH or Plac with weekly sessions in the first 12 weeks and
      monthly sessions thereafter. Assessment for eligibility included standardized
      scales and instruments. After prescreening of 1,480 patients, 518 were evaluated
      for trial participation and 433 were randomized. The main reasons for
      prescreening failure were lack of interest in participating (n = 205),
      difficulties in meeting the time and effort requirements for participation (n =
      186), and contraindications for psychopharmacological treatment with MPH (n =
      194). The full analysis set (FAS) comprised 419 adult ADHD patients (mean age
      35.2 years, males/females 1:1). Fifty-seven percent of the patients suffered from
      the combined ADHD subtype. Prevalence of at least one current or lifetime axis-I
      comorbidity was 66 %. Axis-II comorbidity rates was 18 % (patients with comorbid
      borderline and antisocial personality disorders were excluded). Our network was
      able to recruit an adult ADHD sample essentially comparable to community samples.
      A selection bias was created by excluding patients unable or unwilling to
      participate, or who had somatic and psychiatric contraindications for stimulant
      treatment (Current Controlled Trials ISRCTN54096201, FUNDING: Federal Ministry of
      Education and Research 01GV0606).

PMID- 24132868
TI  - Tailoring the LCST of PNIPAAM-b-PLA-b-PNIPAAM triblock copolymers via
      stereocomplexation.
AB  - Poly(N-isopropylacrylamide)-block-poly(l-lactic acid)-block-poly(N
      isopropylacrylamide) (PNIPAAM-b-PLLA-b-PNIPAAM) and PNIPAAM-b-PDLA-b-PNIPAAM
      triblock copolymers with varying polylactic acid (PLA) lengths are synthesized
      using a combination of ring-opening polymerization and atom-transfer radical
      polymerization. Results of (1) H NMR and gel permeation chromatography analyses
      show that the copolymers have a well-defined triblock structure and the PLA
      segment lengths can be readily controlled with monomer feed ratio.
      Stereocomplexation between the enantiomeric PLA segments is confirmed with
      differential scanning calorimetry and wide-angle X-ray scattering. Dynamic light
      scattering experiments show that (1) the LCST of PNIPAAM in water could be
      tailored from 32  degrees C up to 38.5  degrees C by increasing the length of PLA
      segments and mixing copolymers of similar molecular weight with enantiomeric PLA
      segments to induce stereocomplexation, and (2) the LCST of each mixed copolymer
      system could be tailored within a 2-3  degrees C range of body temperature by
      manipulating the ratio of the enantiomeric copolymers in solution. 

PMID- 24132869
TI  - A new option for glycemic control: insulin degludec, a new-generation basal
      insulin with an ultralong duration of action.
AB  - Basal insulin represents an essential tool in the treatment of diabetes mellitus;
      it can be prescribed with oral antidiabetic agents for the management of type 2
      diabetes (T2D) or used as part of a basal-bolus regimen in type 1 diabetes (T1D)
      and more advanced T2D. The basal insulin products currently on the market,
      although improved, do not optimally mimic endogenous insulin secretion. It is
      therefore important to investigate how the action of a basal insulin can be
      improved to match the physiologic profile more precisely and consequently to
      examine the desired properties of an ideal new-generation basal insulin. Some of
      these characteristics would include stable pharmacokinetic (PK) and
      pharmacodynamic (PD) profiles, true 24-hour duration of action in all patients,
      low within-person variability in absorption and glucose-lowering action, more
      flexible dose timing, and low occurrence of hypoglycemia. A new-generation basal
      insulin, insulin degludec, currently approved in Japan, Mexico, and Europe, was
      designed to provide a more stable pharmacotherapeutic option with a lower risk of
      hypoglycemia than the currently available basal insulins while retaining an
      efficacious profile. The characteristics of an ideal basal insulin are reviewed,
      and the pharmacology and clinical attributes of insulin degludec are discussed. 

PMID- 24132870
TI  - Attention problems and pathological gaming: resolving the 'chicken and egg' in a
      prospective analysis.
AB  - Pathological gaming (PG) behaviors are behaviors which interfere with other life
      responsibilities. Continued debate exists regarding whether symptoms of PG
      behaviors are a unique phenomenon or arise from other mental health problems,
      including attention problems. Development of attention problems and occurrence of
      pathological gaming in 144 adolescents were followed during a 1-year prospective
      analysis. Teens and their parents reported on pathological gaming behaviors,
      attention problems, and current grade point average, as well as several social
      variables. Results were analyzed using regression and path analysis. Attention
      problems tended to precede pathological gaming behaviors, but the inverse was not
      true. Attention problems but not pathological gaming predicted lower GPA 1 year
      later. Current results suggest that pathological gaming arises from attention
      problems, but not the inverse. These results suggest that pathological gaming
      behaviors are symptomatic of underlying attention related mental health issues,
      rather than a unique phenomenon.

PMID- 24132871
TI  - Development of polycaprolactone porous scaffolds by combining solvent casting,
      particulate leaching, and polymer leaching techniques for bone tissue
      engineering.
AB  - Sodium chloride and polyethylene glycol (PEG) were used as water-soluble porogens
      for the formation of porous polycaprolactone (PCL) scaffolds. The main purpose
      was to prepare and evaluate in vitro efficacy of highly interconnected, three
      dimensional, porous polymeric scaffolds, as obtained from the combined
      particulate and polymer leaching techniques. Microscopic analysis confirmed the
      high interconnectivity of the pores and relatively uniform pore size of 378-435
      MUm. The PCL scaffolds were further characterized for their density and pore
      characteristics, water absorption and flow behaviors, and mechanical properties
      and the potential for their use as bone scaffolding materials was evaluated in
      vitro using mouse calvaria-derived preosteoblastic cells (MC3T3-E1). Evidently,
      the use of PEG as the secondary porogen not only improved the interconnectivity
      of the pore structures but also resulted in the PCL scaffolds that exhibited much
      better support for the proliferation and differentiation of the cultured bone
      cells.

PMID- 24132872
TI  - Utility of anthropometric measures in a multiethnic population: their association
      with prevalent diabetes, hypertension and other chronic disease comorbidities.
AB  - Body mass index (BMI) and waist circumference (WC) are two common anthropometric
      measures of obesity in clinical and public health practice. Consensus, however,
      remains elusive regarding their utility for predicting cardiovascular disease
      risk in multiethnic populations. We address this gap in the literature by
      analyzing cross-sectional data from the first round of the Los Angeles County
      Health and Nutrition Examination Survey, 2011. We characterized the relationships
      between BMI, WC, waist-to-hip ratios, waist-to-height ratios, and chronic disease
      extent, as confirmed by the presence of hypertension, diabetes, and/or two or
      more other chronic conditions as defined by a composite indicator 'comorbidity'.
      To account for race/ethnicity, age, gender, and cigarette smoking frequency,
      adjusted odds ratios (aOR) were generated and reported for each of the regression
      analyses. Whereas being overweight was associated with hypertension alone (aOR
      2.10; 95% CI 1.12-3.94), obesity was associated with hypertension (aOR 5.04; 95%
      CI 2.80-9.06) as well as diabetes (aOR 5.28; 95% CI 2.25-12.3) and comorbidity
      (aOR 3.69; 95% CI 2.02-6.77). In whites and African-Americans, BMI and WC were
      positively related to diabetes, hypertension and comorbidity. In Hispanics, BMI
      and WC were also positively related to diabetes and comorbidity, but only the
      former measure was associated with hypertension (p < 0.050). In Asians, BMI was
      not a significant predictor of diabetes, hypertension and/or comorbidity.
      Collectively, the findings suggest that BMI is not universally informative and
      waist circumference and its derivatives may represent a viable, more
      racially/ethnically appropriate alternative for use with selected minority
      groups.

PMID- 24132874
TI  - Risk of docetaxel-induced peripheral neuropathy among 1,725 Danish patients with
      early stage breast cancer.
AB  - Docetaxel-induced peripheral neuropathy (PN) can lead to sub-optimal treatment in
      women with early breast cancer. Here, we compare the frequency of dose reduction
      as a result of PN in two different adjuvant regimens. From the Danish Breast
      Cancer Cooperative Group READ trial we included 1,725 patients with early stage
      breast cancer who randomly were assigned to three cycles of epirubicin and
      cyclophosphamide followed by three cycles docetaxel (D100) or six cycles of
      cyclophosphamide and docetaxel (D75). Eligible patients completed chemotherapy,
      received docetaxel, and provided information on patient-reported outcome
      (secondary outcome of trial) including PN. Associations between PN and risk
      factors were analyzed by multivariate logistic regression. Overall 597 patients
      (34 %) reported PN, grades 2-4, during treatment, 194 (11 %) after the first
      cycle [early onset peripheral neuropathy (EPN)] and 403 (23 %) after subsequent
      cycles [later-onset peripheral neuropathy (LPN)]. The odds ratio (OR) of EPN was
      significantly increased for the D100 regimen (OR 3.10; 95 % CI 2.18-4.42) while
      this regimen was associated with reduced OR of LPN (OR 0.69; 95 % CI 0.54-0.88).
      Patients with PN received significantly lower cumulative doses of docetaxel than
      patients with no PN. Explorative analysis showed that OR of PN was significantly
      reduced if patients wore frozen gloves and socks during treatment (OR 0.56; 95 %
      CI 0.38-0.81) in the EPN group. Patients developing PN after the first cycle are
      less likely to receive docetaxel at the planned dose intensity and usage of
      frozen gloves and socks may modify the risk.

PMID- 24132873
TI  - Performance of a motor task learned on levodopa deteriorates when subsequently
      practiced off.
AB  - Studies in animals and in people with Parkinson's disease (PD) demonstrate
      complex effects of dopamine on learning motor tasks; its effect on retention of
      motor learning has received little attention. Recent animal studies demonstrate
      that practicing a task in the off state, when initially learned in the on state,
      leads to progressive deterioration in performance. We measured the acquisition
      and retention of 3 different motor tasks in the presence and absence of levodopa.
      Twenty individuals with Hoehn and Yahr Stage 1.5 to 3 PD practiced the tasks
      daily for two 4-day weeks, one half practicing on L-dopa the first week and off
      the second week. The other half practiced off l-dopa both weeks. The tasks were
      (1) alternate tapping of 2 keys, (2) moving the body toward 2 targets on a
      posturography device, and (3) mirror drawing of a star. For the tapping and body
      movement tests, those who practiced on the first week had a progressive decline
      in performance with practice during week 2, while subjects off during week 1
      maintained or improved. In contrast, for the mirror task, subjects on L-dopa
      initially had much more difficulty completing the task compared to subjects who
      practiced off. Both groups improved with practice the first week and had flat
      performance the second week. These data suggest that performance of speed
      accuracy tasks learned in the on state may progressively worsen if subsequently
      practiced in the off state. In addition, performance, but not learning, of some
      tasks may be impeded by L-dopa.

PMID- 24132875
TI  - Methylaluminum-supported rare-earth-metal dihydrides.

PMID- 24132876
TI  - Efficacy of a Levulinic Acid Plus Sodium Dodecyl Sulfate (SDS)-Based Sanitizer on
      Inactivation of Influenza A Virus on Eggshells.
AB  - Influenza A virus poses a major public health concern and is associated with
      annual epidemics and occasional pandemics. Influenza A H3N2 viruses, which are an
      important cause of human influenza, can infect birds and mammals. Contaminated
      undercooked poultry products including eggs with avian influenza virus constitute
      a possible risk of transmission to humans. In this study, a novel levulinic acid
      plus sodium dodecyl sulfate (SDS) sanitizer was evaluated for eggshell
      decontamination. Influenza A H3N2 virus-inoculated chicken eggshells were treated
      with a 5 % levulinic acid plus 2 % SDS, 2 % levulinic acid plus 1 % SDS, and 0.5
      % levulinic acid plus 0.5 % SDS liquid solution for 1 min. Log reductions of
      viable viruses were observed by plaque assay. The 5 % levulinic acid plus 2 % SDS
      sanitizer provided the greatest level of influenza A H3N2 virus inactivation
      (2.23 log PFU), and differences in virus inactivation were observed for the
      various levulinic acid plus SDS concentrations tested (P <= 0.05). To the best of
      our knowledge, this is the first study demonstrating influenza A H3N2 virus
      inactivation on eggshells using a novel levulinic acid plus SDS sanitizer. The
      sanitizer may be useful for reducing egg contamination and preventing the spread
      of avian influenza virus to humans.

PMID- 24132877
TI  - Estimating twin concordance for bivariate competing risks twin data.
AB  - For twin time-to-event data, we consider different concordance probabilities,
      such as the casewise concordance that are routinely computed as a measure of the
      lifetime dependence/correlation for specific diseases. The concordance
      probability here is the probability that both twins have experienced the event of
      interest. Under the assumption that both twins are censored at the same time, we
      show how to estimate this probability in the presence of right censoring, and as
      a consequence, we can then estimate the casewise twin concordance. In addition,
      we can model the magnitude of within pair dependence over time, and covariates
      may be further influential on the marginal risk and dependence structure. We
      establish the estimators large sample properties and suggest various tests, for
      example, for inferring familial influence. The method is demonstrated and
      motivated by specific twin data on cancer events with the competing risk death.
      We thus aim to quantify the degree of dependence through the casewise concordance
      function and show a significant genetic component.

PMID- 24132878
TI  - Autumn warming reduces the CO2 sink of a black spruce forest in interior Alaska
      based on a nine-year eddy covariance measurement.
AB  - Nine years (2003-2011) of carbon dioxide (CO2) flux were measured at a black
      spruce forest in interior Alaska using the eddy covariance method. Seasonal and
      interannual variations in the gross primary productivity (GPP) and ecosystem
      respiration (RE) were associated primarily with air temperature: warmer
      conditions enhanced GPP and RE. Meanwhile, interannual variation in annual CO2
      balance was controlled predominantly by RE, and not GPP. During these 9 years of
      measurement, the annual CO2 balance shifted from a CO2 sink to a CO2 source, with
      a 9-year average near zero. The increase in autumn RE was associated with autumn
      warming and was mostly attributed to a shift in the annual CO2 balance. The
      increase in autumn air temperature (0.22  degrees C yr(-1)) during the 9 years of
      study was 15 times greater than the long-term warming trend between 1905 and 2011
      (0.015  degrees C yr(-1)) due to decadal climate oscillation. This result
      indicates that most of the shifts in observed CO2 fluxes were associated with
      decadal climate variability. Because the natural climate varies in a cycle of 10
      30 years, a long-term study covering at least one full cycle of decadal climate
      oscillation is important to quantify the CO2 balance and its interaction with the
      climate.

PMID- 24132879
TI  - The influence of body mass index on the functional prognosis of patients with hip
      fracture.
AB  - BACKGROUNDS AND AIMS: To examine the contribution of patient body mass index to
      functional status, physical independence and emotional distress in various age
      groups (third and fourth age) of female hip-fracture patients. METHODS: A sample
      of 123 older females (>65 years) admitted in a major regional hospital with a
      diagnosis of hip fracture participated in this cross-sectional study. The outcome
      measures used in this study were body mass index (BMI), the Modified Barthel
      Index, the Goldberg General Health Questionnaire, the Tinetti Mobility Test and a
      survey collecting data from participants 24-72 h after admission. For our
      analysis, patients were divided into two groups according to their age: <80 years
      (third age) and >81 years (fourth age). In addition, three groups were made
      according to patients' body mass index <24 h prior to surgery: a normal weight
      group, an overweight group and an obese group. An ANCOVA was performed with age
      group as a between-subjects variable (third age, fourth age) and gender,
      educational level, marital status, type of fracture, type of surgery, presence of
      other fractures and BMI as covariates. RESULTS: Patients in the third-age group
      obtained significantly higher values in the Barthel Index (P = 0.040) and the
      Tinetti Mobility Test (P = 0.001) and lower values in the Goldberg General Health
      Questionnaire (P = 0.035) compared to the fourth-age group. When BMI was
      considered, significance was maintained only in the Tinetti Mobility Test.
      CONCLUSIONS: The BMI could be a relevant mediator of the relationship between
      functional decline and the aging process in the transition between third to
      fourth age in females.

PMID- 24132880
TI  - Ruptured omphalocele mimicking gastroschisis in a fetus with Edwards syndrome.

PMID- 24132881
TI  - Sonographic diagnosis of ascariasis causing small bowel obstruction.
AB  - Acute right lower quadrant pain is a common, but nonspecific presenting symptom
      of a wide variety of diseases in children. Sonography (US) can play a significant
      role in the accurate and early diagnosis of right lower quadrant pain. In this
      article, we report a case of small bowel obstruction due to intestinal ascariasis
      diagnosed at bedside US and confirmed by MRI and describe a new US sign of
      intestinal ascariasis.

PMID- 24132882
TI  - Catchment-mediated atmospheric nitrogen deposition drives ecological change in
      two alpine lakes in SE Tibet.
AB  - The south-east margin of Tibet is highly sensitive to global environmental change
      pressures, in particular, high contemporary reactive nitrogen (Nr) deposition
      rates (ca. 40 kg ha(-1)  yr(-1) ), but the extent and timescale of recent
      ecological change is not well prescribed. Multiproxy analyses (diatoms, pigments
      and geochemistry) of (210) Pb-dated sediment cores from two alpine lakes in
      Sichuan were used to assess whether they have undergone ecological change
      comparable to those in Europe and North America over the last two centuries. The
      study lakes have contrasting catchment-to-lake ratios and vegetation cover: Shade
      Co has a relatively larger catchment and denser alpine shrub than Moon Lake. Both
      lakes exhibited unambiguous increasing production since the late 19th to early
      20th. Principle component analysis was used to summarize the trends of diatom and
      pigment data after the little ice age (LIA). There was strong linear change in
      biological proxies at both lakes, which were not consistent with regional
      temperature, suggesting that climate is not the primary driver of ecological
      change. The multiproxy analysis indicated an indirect ecological response to Nr
      deposition at Shade Co mediated through catchment processes since ca. 1930, while
      ecological change at Moon Lake started earlier (ca. 1880) and was more directly
      related to Nr deposition (depleted delta(15) N). The only pronounced climate
      effect was evidenced by changes during the LIA when photoautotrophic groups
      shifted dramatically at Shade Co (a 4-fold increase in lutein concentration) and
      planktonic diatom abundance declined at both sites because of longer ice cover.
      The substantial increases in aquatic production over the last ca. 100 years
      required a substantial nutrient subsidy and the geochemical data point to a major
      role for Nr deposition although dust cannot be excluded. The study also
      highlights the importance of lake and catchment morphology for determining the
      response of alpine lakes to recent global environmental forcing. 

PMID- 24132883
TI  - Upconverting near-infrared light through energy management in core-shell-shell
      nanoparticles.

PMID- 24132889
TI  - Natural history and pregnancy outcome in patients with placental chorioangioma.
AB  - PURPOSE: To evaluate the natural history and outcome of pregnancies in patients
      with placental chorioangioma. METHODS: A total of 16 placentas with a histologic
      diagnosis of chorioangioma were identified, and the natural history and outcome
      of pregnancy were evaluated. This study was approved by the Institutional Ethics
      Committees of our unit, and written informed consent was obtained from all study
      participants. RESULTS: Thirteen of the 16 cases were associated with a wide
      variety of fetal complications. Two-thirds of the cases developed complications
      that either required elective delivery because of fetal distress (n = 4), fetal
      heart failure (n = 1), oligohydramnion (n = 1), and premature labor of
      dichorionic twins (n = 1) or resulted in intrauterine fetal death and termination
      of pregnancy (n = 2). CONCLUSIONS: Placental chorioangioma was associated with
      the development of polyhydramnios, fetal growth restriction, and fetal distress
      in a significant number of cases. The size, vascularity, and location of the
      chorioangioma may be three independent factors of maternal and fetal
      complications. Any of these three factors can influence the outcome of pregnancy.
      Close antenatal examination should be routinely practiced to allow the timely
      diagnosis of early fetal heart failure.

PMID- 24132888
TI  - Novel wave intensity analysis of arterial pulse wave propagation accounting for
      peripheral reflections.
AB  - We present a novel analysis of arterial pulse wave propagation that combines
      traditional wave intensity analysis with identification of Windkessel pressures
      to account for the effect on the pressure waveform of peripheral wave
      reflections. Using haemodynamic data measured in vivo in the rabbit or generated
      numerically in models of human compliant vessels, we show that traditional wave
      intensity analysis identifies the timing, direction and magnitude of the
      predominant waves that shape aortic pressure and flow waveforms in systole, but
      fails to identify the effect of peripheral reflections. These reflections persist
      for several cardiac cycles and make up most of the pressure waveform, especially
      in diastole and early systole. Ignoring peripheral reflections leads to an
      erroneous indication of a reflection-free period in early systole and additional
      error in the estimates of (i) pulse wave velocity at the ascending aorta given by
      the PU-loop method (9.5% error) and (ii) transit time to a dominant reflection
      site calculated from the wave intensity profile (27% error). These errors
      decreased to 1.3% and 10%, respectively, when accounting for peripheral
      reflections. Using our new analysis, we investigate the effect of vessel
      compliance and peripheral resistance on wave intensity, peripheral reflections
      and reflections originating in previous cardiac cycles.

PMID- 24132890
TI  - Festschrift celebrating the career of Ming T. Tsuang.

PMID- 24132891
TI  - Disorders and borders: psychiatric genetics and nosology.
AB  - Over the past century, the definition and classification of psychiatric disorders
      has evolved through a combination of historical trends, clinical observations,
      and empirical research. The current nosology, instantiated in the DSM-5 and ICD
      10, rests on descriptive criteria agreed upon by a consensus of experts. While
      the development of explicit criteria has enhanced the reliability of diagnosis,
      the validity of the current diagnostic categories has been the subject of debate
      and controversy. Genetic studies have long been regarded as a key resource for
      validating the boundaries among diagnostic categories. Genetic epidemiologic
      studies have documented the familiality and heritability of clinically defined
      psychiatric disorders and molecular genetic studies have begun to identify
      specific susceptibility variants. At the same time, there is growing evidence
      from family, twin and genomic studies that genetic influences on psychiatric
      disorders transcend clinical boundaries. Here I review this evidence for cross
      disorder genetic effects and discuss the implications of these findings for
      psychiatric nosology. Psychiatric genetic research can inform a bottom-up
      reappraisal of psychopathology that may help the field move beyond a purely
      descriptive classification and toward an etiology-based nosology.

PMID- 24132892
TI  - A network medicine approach to psychiatric genetics.
AB  - The major psychiatric disorders are complex in nature, meaning that they are
      influenced by multiple environmental and genetic exposures that perturb the
      intricate cellular network, resulting in disease. In general, psychiatric
      diseases are highly heritable but also have important environmental etiologies.
      Environmental influences include neonatal exposures, social environments,
      psychological mechanisms, and abnormal functioning of the neurotransmitter
      system. Molecular influences can be identified using many data types including
      genomics, epigenomics, transcriptomics, metabolomics, and proteomics. The
      emerging field of network medicine offers a new approach to explore the
      complexities of disease development in a framework that considers a holistic,
      rather than a reductionist viewpoint. In this review we explain a general
      framework of how the network medicine approach can provide valuable insight into
      understanding important molecular mechanisms that contribute to the pathogenesis
      of psychiatric disorders.

PMID- 24132893
TI  - On the outside, looking in: a review and evaluation of the comparability of blood
      and brain "-omes".
AB  - In this article, we review studies detailing the correspondence between
      peripheral blood and brain tissue across various domains of high-throughput -omic
      analysis in order to provide a context for evaluating blood-based biomarker
      studies. Specifically, we reviewed seven studies comparing patterns of DNA
      methylation (i.e., an aspect of the epigenome), eight articles comparing patterns
      of gene expression (i.e., the transcriptome), and three articles comparing
      patterns of protein expression (i.e., the proteome). Our review of the epigenomic
      literature suggests that CpG-island methylation levels are generally highly
      correlated (r = 0.90) between blood and brain. Our review of transcriptomic
      studies suggests that between 35% and 80% of known transcripts are present in
      both brain and blood tissue samples; estimates of cross-tissue correlation in
      expression levels were found to range from 0.25 to 0.64, with stronger
      correlations observed among particular subsets of genes. Relative to the
      epigenome and transcriptome, the proteome has not been as fully compared between
      brain and blood samples, highlighting an important area for future work as whole
      proteome profiling methods mature. Beyond reviewing the relevant studies, we
      discuss some of the assumptions, methodological issues, and gaps in knowledge
      that should be addressed in order to better understand how the multiple "-omes"
      of the brain are reflected in the peripheral blood. A better understanding of
      these relationships is a critical precursor to the validation of biomarkers for
      brain disorders.

PMID- 24132894
TI  - A review of neuroimaging studies of young relatives of individuals with
      schizophrenia: a developmental perspective from schizotaxia to schizophrenia.
AB  - In an effort to identify the developing abnormalities preceding psychosis, Dr.
      Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of
      "schizotaxia," and examined brain structure and function in families affected by
      schizophrenia (SZ). Here, we systematically review genetic (familial) high-risk
      (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings
      inform models of SZ etiology, and suggest directions for future research.
      Neuroimaging studies of youth at HR for SZ through the age of 30 were identified
      through a MEDLINE (PubMed) search. There is substantial evidence of gray matter
      volume abnormalities in youth at HR compared to controls, with an accelerated
      volume reduction over time in association with symptoms and cognitive deficits.
      In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the
      most consistently reported finding in HR. There was also consistent evidence of
      smaller hippocampal volume. In functional studies, hyperactivity of the right PFC
      during performance of diverse tasks with common executive demands was
      consistently reported. The only longitudinal fMRI study to date revealed
      increasing left middle temporal activity in association with the emergence of
      psychotic symptoms. There was preliminary evidence of cerebellar and default mode
      network alterations in association with symptoms. Brain abnormalities in
      structure, function and neurochemistry are observed in the premorbid period in
      youth at HR for SZ. Future research should focus on the genetic and environmental
      contributions to these alterations, determine how early they emerge, and
      determine whether they can be partially or fully remediated by innovative
      treatments.

PMID- 24132895
TI  - Taiwan Schizophrenia Linkage Study: lessons learned from endophenotype-based
      genome-wide linkage scans and perspective.
AB  - Taiwan Schizophrenia Linkage Study (TSLS) was initiated with a linkage strategy
      for locating multiple genes, each of small to moderate effect, and aimed to
      recruit a large enough sample of pairs of affected siblings and their families
      ascertained from a multisite study. With a sample of 607 families successfully
      recruited, a total of 2,242 individuals (1,207 affected and 1,035 unaffected)
      from 557 families were genotyped using 386 microsatellite markers spaced at an
      average of 9-cM intervals. Here the author reviews the establishment of TSLS and
      initial signal derived from linkage scan using the diagnosis of schizophrenia.
      Based on the limited success of the initial linkage analysis, a sufficient
      component causal model is proposed to incorporate endophenotypes and genes for
      schizophrenia. Four types of candidate endophenotype measured in TSLS, including
      schizotypal personality, Continuous Performance Test, Wisconsin Card Sorting
      Test, and niacin skin flush test, are briefly described. The author discusses
      different strategies of linkage analysis incorporating these endophenotypes,
      including quantitative trait loci (QTL) linkage analysis, clustering-derived
      subgroups, ordered subset analysis (OSA), and latent classes for linkage scan.
      Then the author summarizes the linkage signals generated from seven studies of
      endophenotype-based linkage analysis using TSLS, including QTL scan of
      neurocognitive performance, QTL scan of niacin skin flush, the family cluster of
      attention deficit and execution deficit, OSA by schizophrenia-schizotypy factors,
      nested OSA by age at onset and neurocognitive performance, and the latent class
      of deficit schizophrenia for linkage analysis. The perspective of combining next
      generation sequencing with linkage analysis of families is also discussed.

PMID- 24132896
TI  - Heterogeneity of schizophrenia: Genetic and symptomatic factors.
AB  - Schizophrenia may have etiological heterogeneity, and may reflect common
      symptomatology caused by many genetic and environmental factors. In this review,
      we show the potential existence of heterogeneity in schizophrenia based on the
      results of our previous studies. In our study of the NOTCH4 gene, there were no
      significant associations between any single nucleotide polymorphisms (SNPs) of
      NOTCH4 and schizophrenia. However, exploratory analyses suggested that the SNP,
      rs3134928 may be associated with early-onset schizophrenia, and that rs387071 may
      be associated with schizophrenia characterized by negative symptoms. In our
      highly familial schizophrenia study, the African-American cohort without
      environmental exposure showed a possible linkage at marker 8p23.1 in the dominant
      model and in the European-American cohort, a marker at 22q13.32 showed a probable
      linkage in the recessive model. In the less familial schizophrenia families,
      these linkages were not shown. Based on our eye movement study, a putative
      subtype of schizophrenia with severe symptoms related to excitement/hostility,
      negative symptoms and disorganization may be associated with chromosome 22q11. We
      consider that a sample stratification approach may clarify the heterogeneity of
      schizophrenia. Therefore, this approach may lead to a more straightforward way of
      identifying susceptibility genes of schizophrenia.

PMID- 24132897
TI  - The New England Family Study High-risk Project: neurological impairments among
      offspring of parents with schizophrenia and other psychoses.
AB  - This manuscript presents the design and initial outcomes of the New England
      Family Study's (NEFS) High-Risk Project, one of the few epidemiologically
      representative cohorts that has prospectively followed a large sample of
      offspring of parents with both affective and non-affective psychotic disorders
      from the fetal period forward. The goals of this report are: (1) to describe in
      some detail the design, data collection methods, and resulting sample of this
      project; and (2) to prospectively identify and compare rates of childhood
      neurological impairments among offspring of psychotic and nonpsychotic parents,
      with a particular emphasis on offspring risk in relation to specific classes of
      parental psychosis (i.e., affective vs. non-affective psychosis). The
      investigators identified a pool of 755 parents with potential psychotic
      disorders, located over 80% of these and confirmed psychotic diagnoses for 212
      affected parents and 132 unaffected control parents. At birth, the 259 offspring
      of parents with psychosis had approximately a twofold increased risk of abnormal
      neurological functioning compared to offspring of families with no psychotic
      history. This was most pronounced among the 58 offspring of parents with
      schizophrenia. Similar trends were observed at ages 1 and 7 years although these
      did not reach statistical significance. Neither at birth nor at any of the follow
      up assessments were the 157 offspring of parents with affective psychosis found
      to be at elevated risk of neurological impairment. Implications for future
      research and potential preventive interventions for at-risk individuals are
      discussed.

PMID- 24132898
TI  - What can we learn about schizophrenia from studying the human model, drug-induced
      psychosis?
AB  - When drug-induced psychoses were first identified in the mid-20th century,
      schizophrenia was considered a discrete disease with a likely genetic cause.
      Consequently, drug-induced psychoses were not considered central to understanding
      schizophrenia as they were thought to be phenocopies rather than examples of the
      illness secondary to a particular known cause. However, now that we know that
      schizophrenia is a clinical syndrome with multiple component causes, then it is
      clear that the drug-induced psychoses have much to teach us. This article shows
      how the major neuropharmacological theories of schizophrenia have their origins
      in studies of the effects of drugs of abuse. Research into the effects of LSD
      initiated the serotonergic model; amphetamines the dopamine hypothesis, PCP and
      ketamine the glutamatergic hypothesis, while most recently the effects of
      cannabis have provoked interest in the role of endocannabinoids in schizophrenia.
      None of these models account for the complete picture of schizophrenia; rather
      the various drug models mimic different aspects of the illness. Determining the
      different molecular effects of those drugs whose pharmacological effects do and
      do not mimic the various aspects of schizophrenia has much to teach us concerning
      the pathogenesis of the illness.

PMID- 24132899
TI  - Next-generation sequencing in schizophrenia and other neuropsychiatric disorders.
AB  - Schizophrenia is a debilitating lifelong illness that lacks a cure and poses a
      worldwide public health burden. The disease is characterized by a heterogeneous
      clinical and genetic presentation that complicates research efforts to identify
      causative genetic variations. This review examines the potential of current
      findings in schizophrenia and in other related neuropsychiatric disorders for
      application in next-generation technologies, particularly whole-exome sequencing
      (WES) and whole-genome sequencing (WGS). These approaches may lead to the
      discovery of underlying genetic factors for schizophrenia and may thereby
      identify and target novel therapeutic targets for this devastating disorder.

PMID- 24132900
TI  - Genome-wide association study of atypical psychosis.
AB  - Atypical psychosis with a periodic course of exacerbation and features of major
      psychiatric disorders [schizophrenia (SZ) and bipolar disorder (BD)] has a long
      history in clinical psychiatry in Japan. Based upon the new criteria of atypical
      psychosis, a Genome-Wide Association Study (GWAS) was conducted to identify the
      risk gene or variants. The relationships between atypical psychosis, SZ and BD
      were then assessed using independent GWAS data. Forty-seven patients with solid
      criteria of atypical psychosis and 882 normal controls (NCs) were scanned using
      an Affymetrics 6.0 chip. GWAS SZ data (560 SZ cases and 548 NCs) and GWAS BD (107
      cases with BD type 1 and 107 NCs) were compared using gene-based analysis. The
      most significant SNPs were detected around the CHN2/CPVL genes (rs245914, P = 1.6
      * 10(-7)) , COL21A1 gene (rs12196860, P = 2.45 * 10(-7) ), and PYGL/TRIM9 genes
      (rs1959536, P = 7.73 * 10(-7) ), although none of the single-nucleotide
      polymorphisms exhibited genome-wide significance (P = 5 * 10(-8) ). One of the
      highest peaks was detected on the major histocompatibility complex region, where
      large SZ GWASs have previously disclosed an association. The gene-based analysis
      suggested significant enrichment between SZ and atypical psychosis (P = 0.01),
      but not BD. This study provides clues about the types of patient whose diagnosis
      lies between SZ and BD. Studies with larger samples are required to determine the
      causal variant.

PMID- 24132901
TI  - Development of liability syndromes for schizophrenia: where did they come from
      and where are they going?
AB  - Three decades after Paul Meehl proposed the term "schizotaxia" to describe a
      conceptual framework for understanding the liability to schizophrenia, Ming
      Tsuang et al. at Harvard University reformulated the concept as a clinical
      syndrome with provisional research criteria. The reformulated view relied heavily
      on more recent data showing that many non-psychotic, un-medicated biological
      relatives of individuals with schizophrenia showed difficulties in cognitive and
      other clinical functions that resembled those seen in their ill relatives. The
      reformulation raised questions about both whether and when liability could be
      assessed validly in the absence of psychosis, and about the extent to which
      symptoms of liability are reversible. Both questions bear on the larger issue of
      early intervention in schizophrenia. This article reviews the efforts of Tsuang
      et al. to conceptualize and validate schizotaxia as one such syndrome of
      liability. Towards this end, liability is considered first more generally as an
      outcome of interactive genetic and environmental factors. Liability is then
      considered in the context of endophenotypes as a concept that is both broader and
      is potentially more specific (and predictive) than many DSM or ICD diagnostic
      symptoms. Liability syndromes are then considered in the context of their
      proximity to illness, first by reviewing prodromal syndromes (which are more
      proximal), and then by considering schizotaxia, which, as it is currently
      formulated, is pre-prodromal and, therefore, less proximal. Finally, challenges
      to validation and future directions for research are considered.

PMID- 24132902
TI  - Sex differences in the genetic risk for schizophrenia: history of the evidence
      for sex-specific and sex-dependent effects.
AB  - Although there is a long history to examinations of sex differences in the
      familial (and specifically, genetic) transmission of schizophrenia, there have
      been few investigators who have systematically and rigorously studied this issue.
      This is true even in light of population and clinical studies identifying
      significant sex differences in incidence, expression, neuroanatomic and
      functional brain abnormalities, and course of schizophrenia. This review
      highlights the history of work in this arena from studies of family transmission
      patterns, linkage and twin studies to the current molecular genetic strategies of
      large genome-wide association studies. Taken as a whole, the evidence supports
      the presence of genetic risks of which some are sex-specific (i.e., presence in
      one sex and not the other) or sex-dependent (i.e., quantitative differences in
      risk between the sexes). Thus, a concerted effort to systematically investigate
      these questions is warranted and, as we argue here, necessary in order to fully
      understand the etiology of schizophrenia.

PMID- 24132903
TI  - Can sodium/hydrogen exchange inhibitors be repositioned for treating attention
      deficit hyperactivity disorder? An in silico approach.
AB  - Medications for attention deficit hyperactivity disorder (ADHD) are only
      partially effective. Ideally, new treatment targets would derive from a known
      pathophysiology. Such data are not available for ADHD. We combine evidence for
      new etiologic pathways with bioinformatics data to assess the possibility that
      existing drugs might be repositioning for treating ADHD. We use this approach to
      determine if prior data implicating the sodium/hydrogen exchanger 9 gene (SLC9A9)
      in ADHD implicate sodium/hydrogen exchange (NHE) inhibitors as potential
      treatments. We assessed the potential for repositioning by assessing the
      similarity of drug-protein binding profiles between NHE inhibitors and drugs
      known to treat ADHD using the Drug Repositioning and Adverse Reaction via
      Chemical-Protein Interactome server. NHE9 shows a high degree of amino acid
      similarity between NHE inhibitor sensitive NHEs in the region of the NHE
      inhibitor recognition site defined for NHE1. We found high correlations in drug
      protein binding profiles among most ADHD drugs. The drug-protein binding profiles
      of some NHE inhibitors were highly correlated with ADHD drugs whereas the
      profiles for a control set of nonsteroidal anti-inflammatory drugs (NSAIDs) were
      not. Further experimental work should evaluate if NHE inhibitors are suitable for
      treating ADHD.

PMID- 24132904
TI  - Association of genetic risk severity with ADHD clinical characteristics.
AB  - This study sought to examine the association between the cumulative risk severity
      conferred by the total number of attention-deficit/hyperactivity disorder (ADHD)
      risk alleles of the DAT1 3'UTR variable number tandem repeat (VNTR), DRD4 Exon 3
      VNTR, and 5-HTTLPR with ADHD characteristics, clinical correlates, and functional
      outcomes in a pediatric sample. Participants were derived from case-control
      family studies of boys and girls diagnosed with ADHD, a genetic linkage study of
      families with children with ADHD, and a family genetic study of pediatric bipolar
      disorder. Caucasian children 18 and younger with and without ADHD and with
      available genetic data were included in this analysis (N = 591). The association
      of genetic risk severity with sociodemographic, clinical characteristics,
      neuropsychological, emotional, and behavioral correlates was examined in the
      entire sample, in the sample with ADHD, and in the sample without ADHD,
      respectively. Greater genetic risk severity was significantly associated with the
      presence of disruptive behavior disorders in the entire sample and oppositional
      defiant disorder in participants with ADHD. Greater genetic risk severity was
      also associated with the absence of anxiety disorders, specifically with the
      absence of agoraphobia in the context of ADHD. Additionally, one ADHD symptom was
      significantly associated with greater genetic risk severity. Genetic risk
      severity is significantly associated with ADHD clinical characteristics and co
      morbid disorders, and the nature of these associations may vary on the type
      (externalizing vs. internalizing) of the disorder.

PMID- 24132905
TI  - Chromosomal abnormalities in patients with autism spectrum disorders from Taiwan.
AB  - Autism spectrum disorders (ASD) are childhood-onset neurodevelopmental disorders
      characterized by verbal communication impairments, social reciprocity deficits,
      and the presence of restricted interests and stereotyped behaviors. Genetic
      factors contribute to the incidence of ASD evidently. However, the genetic
      spectrum of ASD is highly heterogeneous. Chromosomal abnormalities contribute
      significantly to the genetic deficits of syndromic and non-syndromic ASD. In this
      study, we conducted karyotyping analysis in a sample of 500 patients (447 males,
      53 females) with ASD from Taiwan, the largest cohort in Asia, to the best of our
      knowledge. We found three patients having sex chromosome aneuploidy, including
      two cases of 47, XXY and one case of 47, XYY. In addition, we detected a novel
      reciprocal chromosomal translocation between long arms of chromosomes 4 and 14,
      designated t(4;14)(q31.3;q24.1), in a patient with Asperger's disorder. This
      translocation was inherited from his unaffected father, suggesting it might not
      be pathogenic or it needs further hits to become pathogenic. In line with other
      studies, our study revealed that subjects with sex chromosomal aneuploidy are
      liable to neurodevelopmental disorders, including ASD, and conventional
      karyotyping analysis is still a useful tool in detecting chromosomal
      translocation in patients with ASD, given that array-based comparative genomic
      hybridization technology can provide better resolution in detecting copy number
      variations of genomic DNA.

PMID- 24132906
TI  - Sex-specific association of a common variant of the XG gene with autism spectrum
      disorders.
AB  - Autism spectrum disorders (ASD) are much more common in males than in females.
      Studies using both linkage and candidate gene association approaches have
      identified genetic variants specific to families in which all affected cases were
      male, suggesting that sex may interact with or otherwise influence the expression
      of specific genes in association with ASD. In this study, we specifically
      evaluated the sex-specific genetic effects of ASD with a family-based genome-wide
      association study approach using the data from the Autism Genetic Resource
      Exchange repository. We evaluated the male-specific genetic effects of ASD in 374
      multiplex families of European ancestry in which all affected were male (male
      only; MO) and identified a novel genome-wide significant association in the
      pseudoautosomal boundary on chromosome Xp22.33/Yp11.31 in the MO families of
      predominantly paternal origin (rs2535443, p = 3.8 * 10(-8) ). Five markers that
      reside within a 550 kb intergenic region on chromosome 13q33.3, between the MYO16
      and IRS2 genes, also showed suggestive association with ASD in the MO families (p
      = 3.3 * 10(-5) to 5.3 * 10(-7) ). In contrast, none of these markers appeared to
      be associated with ASD in the families containing any affected females. Our
      results suggest that the pseudoautosomal boundary on Xp22.33/Yp11.31 may harbor
      male-specific genetic variants for ASD.

PMID- 24132909
TI  - Inverse probability weighting in nested case-control studies with additional
      matching--a simulation study.
AB  - Nested case-control designs are inevitably less efficient than full cohort
      designs, and it is important to use available information as efficiently as
      possible. Reuse of controls by inverse probability weighting may be one way to
      obtain efficiency improvements, and it can be particularly advantageous when two
      or more endpoints are analyzed in the same cohort. The controls in a nested case
      control design are often matched on additional factors than at risk status, and
      this should be taken into account when reusing controls. Although some studies
      have suggested methods for handling additional matching, a thorough investigation
      of how this affects parameter estimates and weights is lacking. Our aim is to
      provide such a discussion to help developing guidelines for practitioners. We
      demonstrate that it is important to adjust for the matching variables in
      regression analyses when the matching is broken. We present three types of
      estimators for the inverse sampling probabilities accounting for additional
      matching. One of these estimators was somewhat biased when the cases and controls
      were matched very closely. We investigated how additional matching affected
      estimates of interest, with varying degree of association between the matching
      variables and exposure/outcome. Strong associations introduced only a small bias
      when the matching variables were properly adjusted for. Sometimes, exposure
      variables, for example, blood samples, are analyzed in batches. Rather, strong
      batch effects had to be present before this introduced much bias when the
      matching was broken. All simulations are based on a study of prostate cancer and
      vitamin D.

PMID- 24132907
TI  - Genetics of brain structure: contributions from the Vietnam Era Twin Study of
      Aging.
AB  - Understanding the genetics of neuropsychiatric disorders requires an
      understanding of the genetics of brain structure and function. The Vietnam Era
      Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on
      cognitive and brain aging. Here, we describe basic science work carried out
      within the VETSA MRI study that provides meaningful contributions toward the
      study of neuropsychiatric disorders. VETSA produced the first comprehensive
      assessment of the heritability of cortical and subcortical brain structure sizes,
      all within the same individuals. We showed that neocortical thickness and surface
      area are largely genetically distinct. With continuous neocortical thickness
      maps, we demonstrated regional specificity of genetic influences, and that
      genetic factors did not conform to traditional regions of interest (ROIs).
      However, there was some evidence for different genetic factors accounting for
      different types of cortex, and for genetic relationships across cortical regions
      corresponding to anatomical and functional connectivity and brain maturation
      patterns. With continuous neocortical surface area maps, we confirmed the
      anterior-posterior gradient of genetic influences on cortical area patterning
      demonstrated in animal models. Finally, we used twin methods to create the first
      map of cortical ROIs based entirely on genetically informative data. We conclude
      that these genetically based cortical phenotypes may be more appropriate for
      genetic studies than traditional ROIs based on structure or function. Our results
      also suggest that cortical volume-the product of thickness and surface area-is a
      problematic phenotype for genetic studies because two independent sets of genes
      may be obscured. Examples supporting the validity of these conclusions are
      provided.

PMID- 24132908
TI  - Gene-environment interaction of ApoE genotype and combat exposure on PTSD.
AB  - Factors determining who develops PTSD following trauma are not well understood.
      The ?4 allele of the apolipoprotein E (apoE) gene is associated with dementia and
      unfavorable outcome following brain insult. PTSD is also associated with
      dementia. Given evidence that psychological trauma adversely affects the brain,
      we hypothesized that the apoE genotype moderates effects of psychological trauma
      on PTSD pathogenesis. To investigate the moderation of the relationship between
      PTSD symptoms and combat exposure, we used 172 participants with combat trauma
      sustained during the Vietnam War. PTSD symptoms were the dependent variable and
      number of combat experiences, apoE genotype, and the combat experiences * apoE
      genotype interaction were predictors. We also examined the outcome of a diagnosis
      of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat * apoE genotype
      interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis
      (P = .009). ApoE genotype moderates the relationship between combat exposure and
      PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the
      ?4 allele is related to reduced resilience of the brain to insult. Our results
      are consistent with the ?4 allele influencing the effects of psychological trauma
      on the brain, thereby affecting the risk of PTSD.

PMID- 24132910
TI  - Barriers to effective treatment of pediatric solid tumors in middle-income
      countries: can we make sense of the spectrum of nonbiologic factors that
      influence outcomes?
AB  - BACKGROUND: The delivery of effective treatment for pediatric solid tumors poses
      a particular challenge to centers in middle-income countries (MICs) that already
      are vigorously addressing pediatric cancer. The objective of this study was to
      improve the current understanding of barriers to effective treatment of pediatric
      solid tumors in MICs. METHODS: An ecologic model centered on pediatric sarcoma
      and expanded to country as the environment was used as a benchmark for studying
      the delivery of solid tumor care in MICs. Data on resources were gathered from 7
      centers that were members of the Central American Association of Pediatric
      Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool.
      Pediatric sarcoma outcomes data were available, were retrieved from hospital
      based cancer registries for 6 of the 7 centers, and were analyzed by country.
      Patients who were diagnosed from January 1, 2000 to December 31, 2009 with
      osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas
      were included in the analysis. To explore correlations between resources and
      outcomes, a pilot performance index was created. RESULTS: The analyses identified
      specific deficits in human resources, communication, quality, and infrastructure.
      The treatment abandonment rate, the proportion of metastatic disease at
      diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall
      survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from
      15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment
      abandonment rate correlated inversely with health economic expenditure per capita
      (r = -0.86; P = .03) and life expectancy at birth (r = -0.93; P = .007). The 4
      year AOS rate correlated inversely with the mortality rate among children aged <5
      years (r = -0.80; P = 0.05) and correlated directly with the pilot performance
      index (r = 0.98; P = 0.005). CONCLUSIONS: Initiatives to improve the
      effectiveness of treatment for pediatric solid tumors in MICs are warranted,
      particularly for pediatric sarcomas. Building capacity and infrastructure,
      improving supportive care and communication, and fostering comprehensive,
      multidisciplinary teams are identified as keystones in Central America. A measure
      that meaningfully describes performance in delivering pediatric cancer care is
      feasible and needed to advance comparative, prospective analysis of pediatric
      cancer care and to define resource clusters internationally.

PMID- 24132912
TI  - Simulating effects of changing climate and CO(2) emissions on soil carbon pools
      at the Hubbard Brook experimental forest.
AB  - Carbon (C) sequestration in forest biomass and soils may help decrease regional C
      footprints and mitigate future climate change. The efficacy of these practices
      must be verified by monitoring and by approved calculation methods (i.e., models)
      to be credible in C markets. Two widely used soil organic matter models - CENTURY
      and RothC - were used to project changes in SOC pools after clear-cutting
      disturbance, as well as under a range of future climate and atmospheric carbon
      dioxide (CO(2) ) scenarios. Data from the temperate, predominantly deciduous
      Hubbard Brook Experimental Forest (HBEF) in New Hampshire, USA, were used to
      parameterize and validate the models. Clear-cutting simulations demonstrated that
      both models can effectively simulate soil C dynamics in the northern hardwood
      forest when adequately parameterized. The minimum postharvest SOC predicted by
      RothC occurred in postharvest year 14 and was within 1.5% of the observed
      minimum, which occurred in year 8. CENTURY predicted the postharvest minimum SOC
      to occur in year 45, at a value 6.9% greater than the observed minimum; the slow
      response of both models to disturbance suggests that they may overestimate the
      time required to reach new steady-state conditions. Four climate change scenarios
      were used to simulate future changes in SOC pools. Climate-change simulations
      predicted increases in SOC by as much as 7% at the end of this century, partially
      offsetting future CO(2) emissions. This sequestration was the product of enhanced
      forest productivity, and associated litter input to the soil, due to increased
      temperature, precipitation and CO(2) . The simulations also suggested that
      considerable losses of SOC (8-30%) could occur if forest vegetation at HBEF does
      not respond to changes in climate and CO(2) levels. Therefore, the source/sink
      behavior of temperate forest soils likely depends on the degree to which forest
      growth is stimulated by new climate and CO(2) conditions.

PMID- 24132911
TI  - Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of
      age?
AB  - RATIONALE: Sensitive outcome measures applicable in different centres to quantify
      and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are
      needed both for clinical care and interventional trials. Chest CT has been
      advocated as such a measure yet there is no validated scoring system in infants.
      OBJECTIVES: The objectives of this study were to standardise CT data collection
      across multiple sites; ascertain the incidence of bronchial dilatation and air
      trapping in newborn screened (NBS) infants with CF at 1 year; and assess the
      reproducibility of Brody-II, the most widely used scoring system in children with
      CF, during infancy. METHODS: A multicentre observational study of early pulmonary
      lung disease in NBS infants with CF at age 1 year using volume-controlled chest
      CT performed under general anaesthetic. MAIN RESULTS: 65 infants with NBS
      diagnosed CF had chest CT in three centres. Small insignificant variations in
      lung recruitment manoeuvres but significant centre differences in radiation
      exposures were found. Despite experienced scorers and prior training, with the
      exception of air trapping, inter- and intraobserver agreement on Brody-II score
      was poor to fair (eg, interobserver total score mean (95% CI) kappa coefficient:
      0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score >= 12 (ie, >= 5%
      maximum possible) by either scorer. CONCLUSIONS: In NBS infants with CF, CT
      changes were very mild at 1 year, and assessment of air trapping was the only
      reproducible outcome. CT is thus of questionable value in infants of this age,
      unless an improved scoring system for use in mild CF disease can be developed.

PMID- 24132913
TI  - Synthesis of five-membered osmacycloallenes and conversion into six-membered
      osmacycloallenes.

PMID- 24132914
TI  - Arthrobacter gyeryongensis sp. nov., isolated from soil of a Gynostemma
      pentaphyllum field.
AB  - A Gram-stain-positive, flagellate, rod-shaped, catalase- and oxidase-positive
      bacterium, designated DCY72(T), was isolated from the soil of a Gynostemma
      pentaphyllum field. Growth occurred at 4-34  degrees C (optimum 30  degrees C),
      at pH 4-10 (optimum pH 7), and with 0-5% NaCl (w/v). The major menaquinones of
      strain DCY72(T) were MK-9(H2) (81.0 %) and MK-10(H2) (12.2%). The major amino
      acid present in the cell-wall peptidoglycan was L-lysine. The major fatty acids
      were anteiso-C(15 : 0) and anteiso-C(17 : 0). The genomic DNA G+C content was
      64.5 mol%. 16S rRNA gene sequence analysis revealed that strain DCY72(T) belonged
      to the family Micrococcaceae and was most closely related to Arthrobacter ramosus
      CCM 1646(T) (98.2% similarity). The DNA-DNA relatedness between strain DCY72(T)
      and A. ramosus KACC 14391(T) (98.2% 16S rRNA gene sequence similarity),
      Arthrobacter nitroguajacolicus KACC 14581(T) (97.6%), Arthrobacter nicotinovorans
      KACC 20508(T) (97.3%) and Arthrobacter aurescens KACC 20528(T) (97.3%). was 12.9%
      +/- 0.3, 25.6% +/- 0.3, 26.6% +/- 0.5 and 23.2% +/- 0.9, respectively. On the
      basis of the phenotypic characteristics, genotypic analysis and physiological
      characteristics, strain DCY72(T) represents a novel species of the genus
      Arthrobacter, for which the name Arthrobacter gyeryongensis sp. nov. is proposed.
      The type strain is DCY72(T) ( = KCTC 33072(T) = JCM 18514(T)).

PMID- 24132915
TI  - Mucilaginibacter defluvii sp. nov., isolated from a dye wastewater treatment
      facility.
AB  - A non-motile, rod-shaped bacterium, designated strain A5(T), was isolated from a
      dye wastewater treatment facility in the Republic of Korea. Cells were Gram
      reaction-negative, aerobic, catalase-positive and oxidase-negative. The major
      fatty acids were C(16 : 0), C(18 : 0), iso-C(15 : 0) and summed feature 3 (C16 :
      1)omega6c and/or C(16 : 1omega7c) and the major polar lipid was
      phosphatidylethanolamine. The strain contained MK-7 as the only isoprenoid
      quinone and the DNA G+C content was 41.2 mol%. A phylogenetic tree based on 16S
      rRNA gene sequences showed that strain A5(T) forms an evolutionary lineage within
      the radiation encompassing the members of genus Mucilaginibacter, with
      Mucilaginibacter lutimaris BR-3(T) as its nearest neighbour (96.6% sequence
      similarity). A number of phenotypic characteristics distinguished strain A5(T)
      from the members of the genus Mucilaginibacter. On the basis of the evidence
      presented in this study, strain A5(T) represents a novel species, for which the
      name Mucilaginibacter defluvii sp. nov. is proposed. The type strain is A5(T) ( =
      KCTC 23922(T) = JCM 18283(T)).

PMID- 24132916
TI  - Description of Galbitalea soli gen. nov., sp. nov., and Frondihabitans sucicola
      sp. nov.
AB  - Bacterial strains KIS82-1(T) and GRS42(T) were isolated from soil and from sap of
      Acer mono, respectively, in the Republic of Korea. Both strains were aerobic,
      Gram-stain-positive, mesophilic, rod-shaped and motile. Phylogenetically, both
      strains belonged to the family Microbacteriaceae of the phylum Actinobacteria.
      The 16S rRNA gene sequence of strain KIS82-1(T) showed the highest similarity to
      those of Frondihabitans peucedani RS-15(T) (97.6%), Frigoribacterium mesophilum
      MSL-08(T) (97.2%) and Labedella gwakjiensis KSW2-17(T) (97.0%), while strain
      GRS42(T) showed the highest 16S rRNA gene sequence similarity to Frondihabitans
      peucedani RS-15(T) (98.7%), Frondihabitans cladoniiphilus CafT13(T) (98.4%),
      Frondihabitans australicus E1HC-02(T) (98.2%) and Frigoribacterium faeni 801(T)
      (97.3%). The 16S rRNA gene sequence similarity between GRS42(T) and KIS82-1(T)
      was 97.0%. Phylogenetic trees indicated that strain GRS42(T) was firmly grouped
      into the genus Frondihabitans, while strain KIS82-1(T) did not show a clear
      affiliation to any genus within the family Microbacteriaceae. Strain KIS82-1(T)
      showed type B1beta peptidoglycan with 2,4-diamino-L-butyric acid as the diamino
      acid. It had MK-11, MK-10 and MK-12 as respiratory quinones, anteiso-C(15 : 0),
      iso-C(16: 0) and iso-C(14 : 0) as major cellular fatty acids and
      diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid as
      predominant polar lipids. The peptidoglycan of strain GRS42(T) was of type B2beta
      with D-ornithine as the diamino acid. The strain contained MK-8, MK-9 and MK-7 as
      respiratory quinones, summed feature 8 (C(18 : 1)omega6c and/or C(18 : 1)omega7c)
      as major cellular fatty acid and diphosphatidylglycerol, phosphatidylglycerol and
      three unknown glycolipids as predominant polar lipids. Strain GRS42(T) revealed
      low DNA-DNA hybridization (<50% relatedness) with closely related strains. Based
      on the data obtained in the present polyphasic taxonomic study, we propose that
      strain KIS82-1(T) represents a novel genus and species and that strain GRS42(T)
      represents a novel species in the family Microbacteriaceae. The genus Galbitalea
      gen. nov. is proposed, with strain KIS82-1(T) ( = KACC 15520(T) = NBRC 108727(T))
      as the type strain of the type species, Galbitalea soli sp. nov. Strain GRS42(T)
      ( = KACC 15521(T) = NBRC 108728(T)) is proposed as the type strain of
      Frondihabitans sucicola sp. nov.

PMID- 24132917
TI  - alphaB-crystallin: a novel regulator of breast cancer metastasis to the brain.
AB  - PURPOSE: Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and
      are associated with a high incidence of brain metastases and poor clinical
      outcomes. The molecular chaperone alphaB-crystallin is predominantly expressed in
      triple-negative breast cancer (TNBC) and contributes to an aggressive tumor
      phenotype in preclinical models. We investigated the potential role of alphaB
      crystallin in brain metastasis in TNBCs. EXPERIMENTAL DESIGN: alphaB-crystallin
      expression in primary breast carcinomas and brain metastases was analyzed by
      immunohistochemistry among patients with breast cancer with brain metastases.
      alphaB-crystallin was overexpressed or silenced in two different TNBC cell lines.
      The effects on cell adhesion to human brain microvascular endothelial cells
      (HBMEC) or extracellular matrix proteins, transendothelial migration, and
      transmigration across a HBMEC/astrocyte coculture blood-brain barrier (BBB) model
      were examined. In addition, the effects of overexpressing or silencing alphaB
      crystallin on brain metastasis in vivo were investigated using orthotopic TNBC
      models. RESULTS: In a cohort of women with breast cancer brain metastasis, alphaB
      crystallin expression in primary breast carcinomas was associated with poor
      overall survival and poor survival after brain metastasis, even among patients
      with TNBC. Stable overexpression of alphaB-crystallin in TNBC cells enhanced
      adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro,
      whereas silencing alphaB-crystallin inhibited these events. alphaB-crystallin
      promoted adhesion of TNBC cells to HBMECs, at least in part, through an
      alpha3beta1 integrin-dependent mechanism. alphaB-crystallin overexpression
      promoted brain metastasis, whereas silencing alphaB-crystallin inhibited brain
      metastasis in orthotopic TNBC models. CONCLUSION: alphaB-crystallin is a novel
      regulator of brain metastasis in TNBC and represents a potential biomarker and
      drug target for this aggressive disease.

PMID- 24132918
TI  - Loss of PTEN expression is associated with poor prognosis in patients with
      intraductal papillary mucinous neoplasms of the pancreas.
AB  - PURPOSE: Previously, we reported PIK3CA gene mutations in high-grade intraductal
      papillary mucinous neoplasms (IPMN). However, the contribution of
      phosphatidylinositol-3 kinase pathway (PI3K) dysregulation to pancreatic
      carcinogenesis is not fully understood and its prognostic value unknown. We
      investigated the dysregulation of the PI3K signaling pathway in IPMN and its
      clinical implication. EXPERIMENTAL DESIGN: Thirty-six IPMN specimens were
      examined by novel mutant-enriched sequencing methods for hot-spot mutations in
      the PIK3CA and AKT1 genes. PIK3CA and AKT1 gene amplifications and loss of
      heterozygosity at the PTEN locus were also evaluated. In addition, the expression
      levels of PDPK1/PDK1, PTEN, and Ki67 were analyzed by immunohistochemistry.
      RESULTS: Three cases carrying the E17K mutation in the AKT1 gene and one case
      harboring the H1047R mutation in the PIK3CA gene were detected among the 36
      cases. PDK1 was significantly overexpressed in the high-grade IPMN versus low
      grade IPMN (P = 0.034) and in pancreatic and intestinal-type of IPMN versus
      gastric-type of IPMN (P = 0.020). Loss of PTEN expression was strongly associated
      with presence of invasive carcinoma and poor survival in these IPMN patients (P =
      0.014). CONCLUSION: This is the first report of AKT1 mutations in IPMN. Our data
      indicate that oncogenic activation of the PI3K pathway can contribute to the
      progression of IPMN, in particular loss of PTEN expression. This finding suggests
      the potential employment of PI3K pathway-targeted therapies for IPMN patients.
      The incorporation of PTEN expression status in making surgical decisions may also
      benefit IPMN patients and should warrant further investigation.

PMID- 24132919
TI  - Discrete molecular classes of ovarian cancer suggestive of unique mechanisms of
      transformation and metastases.
AB  - PURPOSE: Tumor heterogeneity and subsistence of high-grade serous ovarian
      adenocarcinoma (HGSC) classes can be speculated from clinical incidences
      suggesting passive tumor dissemination versus active invasion and metastases.
      EXPERIMENTAL DESIGN: We explored this theme toward tumor classification through
      two approaches of gene expression pattern clustering: (i) derivation of a core
      set of metastases-associated genes and (ii) resolution of independent weighted
      correlation networks. Further identification of appropriate cell and xenograft
      models was carried out for resolution of class-specific biologic functions.
      RESULTS: Both clustering approaches achieved resolution of three distinct tumor
      classes, two of which validated in other datasets. Networks of enriched gene
      modules defined biologic functions of quiescence, cell division-differentiation
      lineage commitment, immune evasion, and cross-talk with niche factors. Although
      deviant from normal homeostatic mechanisms, these class-specific profiles are not
      totally random. Preliminary validation of these suggests that Class 1 tumors
      survive, metastasize in an epithelial-mesenchymal transition (EMT)-independent
      manner, and are associated with a p53 signature, aberrant differentiation, DNA
      damage, and genetic instability. These features supported by association of cell
      specific markers, including PAX8, PEG3, and TCF21, led to the speculation of
      their origin being the fimbrial fallopian tube epithelium. On the other hand,
      Class 2 tumors activate extracellular matrix-EMT-driven invasion programs (Slug,
      SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are
      prospectively suggestive of ovarian surface epithelium associated wound healing
      mechanisms. Further validation of these etiologies could define a new therapeutic
      framework for disease management.

PMID- 24132920
TI  - A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate,
      administered by intravenous infusion once weekly in patients with
      relapsed/refractory B-cell non-Hodgkin lymphoma.
AB  - PURPOSE: To determine recommended dose, dose-limiting toxicity, safety profile,
      pharmacokinetics, preliminary antitumor activity, and exploratory
      pharmacodynamics of SAR3419, an antibody-drug conjugate targeting CD19,
      administered alone by intravenous infusion weekly (qw), in a dose-escalation
      phase I study in patients with refractory/relapsed (R/R) non-Hodgkin lymphoma
      (NHL). EXPERIMENTAL DESIGN: Patients with R/R CD19(+) B-NHL were treated with
      escalating doses of SAR3419 repeated qw for eight to 12 doses. On the basis of
      clinical evidence of late or cumulative toxicities, the study protocol was
      amended to test an "optimized" administration schedule consisting of four qw
      doses followed by four biweekly (q2w) doses (qw/q2w) at the recommended dose with
      the intent of reducing drug accumulation. RESULTS: Forty-four patients were
      treated on seven dose levels ranging from 5 to 70 mg/m(2). SAR3419 recommended
      dose was determined as 55 mg/m(2) qw. Twenty-five patients received the qw/q2w
      schedule at 55 mg/m(2), which showed an improved safety profile compared with the
      qw schedule. Antilymphoma activity was observed with both schedules in around 30%
      of patients with either indolent or aggressive diseases. SAR3419 displayed a long
      terminal half-life (approximately 7 days) and a low clearance (approximately 0.6
      L/d), with no dose effect. The qw/q2w schedule allowed limiting accumulation with
      a decrease in SAR3419 plasma trough and average concentrations by around 1.4-fold
      compared with the qw schedule. CONCLUSION: While administered weekly, SAR3419 is
      well tolerated and active. The qw/q2w schedule that shows an improved safety
      profile and preserves antilymphoma activity is selected for clinical phase II
      studies.

PMID- 24132921
TI  - Large-scale analysis of PDGFRA mutations in melanomas and evaluation of their
      sensitivity to tyrosine kinase inhibitors imatinib and crenolanib.
AB  - PURPOSE: Platelet-derived growth factor receptor alpha (PDGFRA) is a target for
      tyrosine kinase inhibitor (TKI)-based targeted therapy. Dysregulation of PDGFRA
      has been reported in many cancers. However, PDGFRA mutations in melanomas have
      not been well studied. We analyzed the genetic mutations of PDGFRA in Chinese
      patients with melanoma and determined the inhibitory potency of TKIs, such as
      imatinib and crenolanib, on mutant PDGFRA. EXPERIMENTAL DESIGN: Of note, 351
      melanoma tissue samples were examined for genetic mutations in exons 12, 14, and
      18 of PDGFRA. Activities of mutations in response to imatinib and crenolanib were
      analyzed by Western blotting of tyrosine-phosphorylated PDGFRA and cell
      proliferation assays. RESULTS: PDGFRA mutations were observed in 4.6% (16 of 351)
      of melanomas, and these mutations were mainly detected in acral and mucosal
      melanomas. PDGFRA mutations seem to be mutually exclusive with KIT mutations, but
      may coexist with BRAF and NRAS mutations. The genetic mutations of PDGFRA were
      unrelated to the age, thickness, and ulceration status of primary melanomas.
      Thirteen mutations were not reported before, and five (P577S, V658A, R841K,
      H845Y, and G853D) of them resulted in strong autophosphorylation of PDGFRA.
      Crenolanib showed higher potency than imatinib in inhibiting the kinase activity
      of PDGFRA. Except that V658A mutation was imatinib-resistant, all the other
      mutations were sensitive to both imatinib and crenolanib. CONCLUSIONS: PDGFRA
      mutations are detected in a small population of melanoma patients. Our study
      suggests that patients with melanoma harboring certain PDGFRA mutations may
      benefit from imatinib and crenolanib treatment.

PMID- 24132922
TI  - Phase I trial of preoperative chemoradiation plus sorafenib for high-risk
      extremity soft tissue sarcomas with dynamic contrast-enhanced MRI correlates.
AB  - PURPOSE: We conducted a phase I trial of the addition of sorafenib to a
      chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5
      cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a
      correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to
      assess response to treatment. EXPERIMENTAL DESIGN: Patients were treated at
      increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice
      daily) initiated 14 days before three preoperative and three postoperative cycles
      of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with
      epirubicin omitted. The primary objective was to determine the maximum tolerated
      dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of
      sorafenib, and before surgery. The imaging data were subjected to quantitative
      pharmacokinetic analyses. RESULTS: Eighteen subjects were enrolled, of which 16
      were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3-4 adverse
      events included neutropenia (94%), hypophosphatemia (75%), anemia (69%),
      thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38%
      developed wound complications requiring surgical intervention. The rate of >=95%
      histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker
      DeltaK(trans) after 2 weeks of sorafenib correlated with histologic response
      (R(2) = 0.67, P = 0.012) at surgery. CONCLUSION: The addition of sorafenib to
      preoperative chemoradiotherapy is feasible and warrants further investigation in
      a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of
      sorafenib and may be a minimally invasive tool for rapid assessment of drug
      effect in soft tissue sarcoma.

PMID- 24132923
TI  - Development, characterization, and reversal of acquired resistance to the MEK1
      inhibitor selumetinib (AZD6244) in an in vivo model of childhood astrocytoma.
AB  - PURPOSE: The BT-40 low-grade childhood astrocytoma xenograft model expresses
      mutated BRAF(V600E) and is highly sensitive to the MEK inhibitor selumetinib
      (AZD6244). In this study, we developed and characterized selumetinib resistance
      and explored approaches to circumventing the mechanisms of acquired resistance.
      EXPERIMENTAL DESIGN: BT-40 xenografts were selected in vivo for selumetinib
      resistance. Resistant tumors were obtained and characterized, as were tumors that
      reverted to sensitivity. Characterization included expression profiling,
      assessment of MEK signature and compensatory pathways, MEK inhibition, BRAF
      expression, and cytokine levels. Combination treatment of BT-40/AZD-resistant
      tumors with the MEK inhibitor and a STAT3 inhibitor (LLL12) was assessed.
      RESULTS: Resistance was unstable, tumors reverting to selumetinib sensitivity
      when passaged in untreated mice, and MEK was equally inhibited in sensitive and
      resistant tumors by selumetinib. Drug resistance was associated with an enhanced
      MEK signature and increased interleukin (IL)-6 and IL-8 expression. Selumetinib
      treatment induced phosphorylation of STAT3 (Y705) only in resistant xenografts,
      and similar results were observed in BRAF(V600E) astrocytic cell lines
      intrinsically resistant to selumetinib. Treatment of BT-40-resistant tumors with
      selumetinib or LLL12 had no significant effect, whereas combined treatment
      induced complete regressions of BT-40/AZD-resistant xenografts. CONCLUSIONS:
      Resistance to selumetinib selected in vivo in BT-40 tumor xenografts was
      unstable. In resistant tumors, selumetinib activated STAT3, and combined
      treatment with selumetinib and LLL12 induced complete responses in resistant BT
      40 tumors. These results suggest dual targeting BRAF (V600E) signaling and STAT3
      signaling may be effective in selumetinib-resistant tumors or may retard or
      prevent onset of resistance.

PMID- 24132925
TI  - Voluntary sterilization for childfree women: understanding patient profiles,
      evaluating accessibility, examining legislation.
AB  - Approximately 47 percent of women ages fifteen to forty-four are currently
      without children, and slightly more than 20 percent of white women in America
      will never bear children, the highest percentage in modern history. Many fertile
      women who are childless are voluntarily so. Although any competent person twenty
      one years or older is legally eligible for voluntary sterilization, many doctors
      refuse to sterilize childfree women. This essay explores various reasons a woman
      would want to continue in her childfree lifestyle, evaluates the accessibility of
      sterilization for women who are childfree by examining the reported reasons for
      denial of sterilization-both from the woman's and the physician's perspective-and
      assesses the legal status of voluntary sterilization for nonparous women. The
      essay also urges physicians to follow recommended guidelines for counseling women
      who, regardless of parity, desire sterilization and to provide this contraception
      if, after careful consideration, there are no outstanding health or other reasons
      that the procedure should not be performed. 

PMID- 24132924
TI  - HAb18G/CD147 promotes pSTAT3-mediated pancreatic cancer development via CD44s.
AB  - PURPOSE: Signal transducer and activator of transcription 3 (STAT3) plays a
      critical role in initiation and progression of pancreatic cancer. However,
      therapeutically targeting STAT3 has failed clinically. We previously identified
      HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed
      to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic
      tumorigenesis in vitro and in vivo. EXPERIMENTAL DESIGN: The expression of
      HAb18G/CD147, pSTAT3, and CD44s was determined in tissue microarrays. The
      tumorigenic function and molecular signaling mechanism of HAb18G/CD147 were
      assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot
      assay, immunofluorescence staining, immunoprecipitation, and in vivo tumor
      formation using loss or gain-of-function strategies. RESULTS: Highly expressed
      HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity
      in vivo. Cyclophilin A (CyPA), a ligand of CD147, stimulated STAT3
      phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147
      dependent mechanisms. HAb18G/CD147 was associated and colocalized with cancer
      stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as
      well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell
      growth. High HAb18G/CD147 expression in pancreatic cancer was significantly
      correlated with the poor tumor differentiation, and the high coexpression of
      HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with
      pancreatic cancer. CONCLUSIONS: We identified HAb18G/CD147 as a novel upstream
      activator of STAT3, which interacts with CD44s and plays a critical role in the
      development of pancreatic cancer. The data suggest that HAb18G/CD147 could be a
      promising therapeutic target for highly aggressive pancreatic cancer and a
      surrogate marker in the STAT3-targeted molecular therapies.

PMID- 24132928
TI  - Causal inference for Mann-Whitney-Wilcoxon rank sum and other nonparametric
      statistics.
AB  - The nonparametric Mann-Whitney-Wilcoxon (MWW) rank sum test is widely used to
      test treatment effect by comparing the outcome distributions between two groups,
      especially when there are outliers in the data. However, such statistics
      generally yield invalid conclusions when applied to nonrandomized studies,
      particularly those in epidemiologic research. Although one may control for
      selection bias by using available approaches of covariates adjustment such as
      matching, regression analysis, propensity score matching, and marginal structural
      models, such analyses yield results that are not only subjective based on how the
      outliers are handled but also often difficult to interpret. A popular alternative
      is a conditional permutation test based on randomization inference [Rosenbaum PR.
      Covariance adjustment in randomized experiments and observational studies.
      Statistical Science 2002; 17(3):286-327]. Because it requires strong and
      implausible assumptions that may not be met in most applications, this approach
      has limited applications in practice. In this paper, we address this gap in the
      literature by extending MWW and other nonparametric statistics to provide causal
      inference for nonrandomized study data by integrating the potential outcome
      paradigm with the functional response models (FRM). FRM is uniquely positioned to
      model dynamic relationships between subjects, rather than attributes of a single
      subject as in most regression models, such as the MWW test within our context.
      The proposed approach is illustrated with data from both real and simulated
      studies.

PMID- 24132929
TI  - gCMAP: user-friendly connectivity mapping with R.
AB  - Connections between disease phenotypes and drug effects can be made by
      identifying commonalities in the associated patterns of differential gene
      expression. Searchable databases that record the impacts of chemical or genetic
      perturbations on the transcriptome--here referred to as 'connectivity maps'-
      permit discovery of such commonalities. We describe two R packages, gCMAP and
      gCMAPWeb, which provide a complete framework to construct and query connectivity
      maps assembled from user-defined collections of differential gene expression
      data. Microarray or RNAseq data are processed in a standardized way, and results
      can be interrogated using various well-established gene set enrichment methods.
      The packages also feature an easy-to-deploy web application that facilitates
      reproducible research through automatic generation of graphical and tabular
      reports. AVAILABILITY AND IMPLEMENTATION: The gCMAP and gCMAPWeb R packages are
      freely available for UNIX, Windows and Mac OS X operating systems at Bioconductor
      (http://www.bioconductor.org).

PMID- 24132930
TI  - Thymine distribution in genes provides novel insight into the functional
      significance of the proteome of the malaria parasite Plasmodium falciparum 3D7.
AB  - Plasmodium falciparum (Pf)-mediated malaria is one of the most devastating
      diseases in the world, and the search for suitable antimalarial drugs remains an
      extraordinary challenge for scientists working in this area. Novel unconventional
      approaches could reveal new potential targets that may be useful for the
      treatment of malaria. We used a bioinformatics approach to analyze the entire
      genome of the Pf3D7 strain. Because the carbon (C-) content is a pivotal
      parameter that determines the hydrophobicity of a protein, which in turn controls
      protein folding and function, we analyzed the entire Pf3D7 proteome based on the
      gene's thymine (T)-controlled amino acid expression. Our data disclose a total of
      14 proteins encoded by chromosome-4 and chromosome-9 that have an outstanding T
      encoded and C-controlled hydrophobic character. The identification of these
      proteins could open new pivotal drug-targeting avenues.

PMID- 24132931
TI  - MFCompress: a compression tool for FASTA and multi-FASTA data.
AB  - MOTIVATION: The data deluge phenomenon is becoming a serious problem in most
      genomic centers. To alleviate it, general purpose tools, such as gzip, are used
      to compress the data. However, although pervasive and easy to use, these tools
      fall short when the intention is to reduce as much as possible the data, for
      example, for medium- and long-term storage. A number of algorithms have been
      proposed for the compression of genomics data, but unfortunately only a few of
      them have been made available as usable and reliable compression tools. RESULTS:
      In this article, we describe one such tool, MFCompress, specially designed for
      the compression of FASTA and multi-FASTA files. In comparison to gzip and applied
      to multi-FASTA files, MFCompress can provide additional average compression gains
      of almost 50%, i.e. it potentially doubles the available storage, although at the
      cost of some more computation time. On highly redundant datasets, and in
      comparison with gzip, 8-fold size reductions have been obtained. AVAILABILITY:
      Both source code and binaries for several operating systems are freely available
      for non-commercial use at http://bioinformatics.ua.pt/software/mfcompress/.

PMID- 24132932
TI  - Clinical care in craniofacial microsomia: a review of current management
      recommendations and opportunities to advance research.
AB  - Craniofacial microsomia (CFM) is a complex condition associated with microtia,
      mandibular hypoplasia, and preauricular tags. It is the second most common
      congenital facial condition treated in many craniofacial centers and requires
      longitudinal multidisciplinary patient care. The purpose of this article is to
      summarize current recommendations for clinical management and discuss
      opportunities to advance clinical research in CFM.

PMID- 24132933
TI  - Novel "breath figure"-based synthetic PLGA matrices for in vitro modeling of
      mammary morphogenesis and assessing chemotherapeutic response.
AB  - Biodegradable poly(lactic-co-glycolic acid) (PLGA) porous films are developed to
      support mammary cell growth and function. Such porous polymer matrices of PLGA
      are generated using the easily implemented water-templating "breath-figure"
      technique that allows water droplets to penetrate the nascent polymer films to
      create a rough porous polymer film. Such breath figure-based micropatterned
      porous films show higher epithelial differentiation and growth than the
      corresponding flat 2D films, and represent the first instance of using them for
      tissue culture. Specifically, the breath figure morphology supports robust acinar
      growth with almost double the number of lobular-alveolar units compared to the 2D
      cultures. Gene profile analysis indicates that the cells grown on porous polymer
      films show enhanced expressions of mammary differentiation genes (GATA3, EMA, and
      INTEGB4) but lower the expression of mesenchymal gene (CALLA). Hormonal
      stimulation of these cultures dramatically increases expression of progenitor
      marker gene Notch1. Importantly, cells grown on porous PLGA films exhibit an
      enhanced resistance to doxorubicin treatment in comparison to 2D cultures. Breath
      figure PLGA films show promise in mimicking in vivo mammary functions and can
      potentially be used to screen chemotherapeutic drugs. The simplicity and ease of
      fabrication of these polymer films is especially appealing to the development of
      effective biomaterials to support cell culture and differentiation.

PMID- 24132934
TI  - Unexpected isomerism in cis-2 bis(pyrrolidino)[60]fullerene diastereomers.
AB  - Similar yet different: A one-step regio- and diastereoselective synthesis of
      three new bis(pyrrolidine)[60]fullerenes, one cis-1 and two unprecedented cis-2
      diastereoisomers, is reported. The compounds are easily purified using simple
      chromatographic techniques, and were fully characterized by spectroscopic
      techniques and X-ray crystallography. A mechanism for the isomeric conversion
      observed is proposed. 

PMID- 24132935
TI  - Surface modification of polymers for biocompatibility via exposure to extreme
      ultraviolet radiation.
AB  - Polymeric biomaterials are being widely used for the treatment of various
      traumata, diseases and defects in human beings due to ease in their synthesis. As
      biomaterials have direct interaction with the extracellular environment in the
      biological world, biocompatibility is a topic of great significance. The
      introduction or enhancement of biocompatibility in certain polymers is still a
      challenge to overcome. Polymer biocompatibility can be controlled by surface
      modification. Various physical and chemical methods (e.g., chemical and plasma
      treatment, ion implantation, and ultraviolet irradiation etc.) are in use or
      being developed for the modification of polymer surfaces. However an important
      limitation in their employment is the alteration of bulk material. Different
      surface and bulk properties of biomaterials are often desirable for biomedical
      applications. Because extreme ultraviolet (EUV) radiation penetration is quite
      limited even in low density mediums, it could be possible to use it for surface
      modification without influencing the bulk material. This article reviews the
      degree of biocompatibility of different polymeric biomaterials being currently
      employed in various biomedical applications, the surface properties required to
      be modified for biocompatibility control, plasma and laser ablation based surface
      modification techniques, and research studies indicating possible use of EUV for
      enhancing biocompatibility.

PMID- 24132936
TI  - Inferring global network properties from egocentric data with applications to
      epidemics.
AB  - Social networks are often only partly observed, and it is sometimes desirable to
      infer global properties of the network from 'egocentric' data. In the current
      paper, we study different types of egocentric data, and show which global network
      properties are consistent with data. Two global network properties are
      considered: the size of the largest connected component (the giant) and the size
      of an epidemic outbreak taking place on the network. The main conclusion is that,
      in most cases, egocentric data allow for a large range of possible sizes of the
      giant and the outbreak, implying that egocentric data carry very little
      information about these global properties. The asymptotic size of the giant and
      the outbreak is also characterized, assuming the network is selected uniformly
      among networks with prescribed egocentric data. 

PMID- 24132937
TI  - Neuronal and glial alterations, increased anxiety, and cognitive impairment
      before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's
      disease.
AB  - In the context of Alzheimer's disease (AD), hippocampal alterations have been
      well described in advanced stages of the pathology, when amyloid deposition,
      inflammation and glial activation occur, but less attention has been directed to
      studying early brain and behavioral changes. Using an animal model of AD, the
      transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are
      present and low cerebral levels of amyloid peptides are detectable, we found
      structural, morphological, and cellular alterations in the hippocampus. Young
      transgenic mice showed a reduced hippocampal volume with less number of pyramidal
      and granular neurons, which additionally exhibited cell atrophy. The neurogenic
      capability in this zone, measured as DCX+ cells, was strongly diminished and
      associated to alterations in cell maturity. A decrease in presynaptic
      synaptophysin optical density was detected in mossy fibers reaching CA3 subfield
      but not in Golgi stained- CA1 dendritic spine density. Employing confocal
      microscopy and accurate stereological tools we also found a reduction in the
      number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a
      potential detriment of neural support. According with untimely neuroglial
      alterations, young PDAPP mice failed in the novel location recognition test, that
      depends on hippocampal function. Moreover, multivariate statistical analysis of
      the behavioral outcome in the open-field test evidenced an elevated anxiety score
      in Tg mice compared with age-matched control mice. In line with this, the
      transgenic group showed a higher number of c-Fos+ nuclei in central and
      basolateral amygdala, a result that supports the early involvement of the
      emotionality factor in AD pathology. Applying an integrative approach, this work
      focuses on early structural, morphological and functional changes and provides
      new and compelling evidence of behavioral alterations that precede manifest AD.

PMID- 24132938
TI  - Combining markers with and without the limit of detection.
AB  - In this paper, we consider the combination of markers with and without the limit
      of detection (LOD). LOD is often encountered when measuring proteomic markers.
      Because of the limited detecting ability of an equipment or instrument, it is
      difficult to measure markers at a relatively low level. Suppose that after some
      monotonic transformation, the marker values approximately follow multivariate
      normal distributions. We propose to estimate distribution parameters while taking
      the LOD into account, and then combine markers using the results from the linear
      discriminant analysis. Our simulation results show that the ROC curve parameter
      estimates generated from the proposed method are much closer to the truth than
      simply using the linear discriminant analysis to combine markers without
      considering the LOD. In addition, we propose a procedure to select and combine a
      subset of markers when many candidate markers are available. The procedure based
      on the correlation among markers is different from a common understanding that a
      subset of the most accurate markers should be selected for the combination. The
      simulation studies show that the accuracy of a combined marker can be largely
      impacted by the correlation of marker measurements. Our methods are applied to a
      protein pathway dataset to combine proteomic biomarkers to distinguish cancer
      patients from non-cancer patients.

PMID- 24132939
TI  - Wind farm and solar park effects on plant-soil carbon cycling: uncertain impacts
      of changes in ground-level microclimate.
AB  - Global energy demand is increasing as greenhouse gas driven climate change
      progresses, making renewable energy sources critical to future sustainable power
      provision. Land-based wind and solar electricity generation technologies are
      rapidly expanding, yet our understanding of their operational effects on
      biological carbon cycling in hosting ecosystems is limited. Wind turbines and
      photovoltaic panels can significantly change local ground-level climate by a
      magnitude that could affect the fundamental plant-soil processes that govern
      carbon dynamics. We believe that understanding the possible effects of changes in
      ground-level microclimates on these phenomena is crucial to reducing uncertainty
      of the true renewable energy carbon cost and to maximize beneficial effects. In
      this Opinions article, we examine the potential for the microclimatic effects of
      these land-based renewable energy sources to alter plant-soil carbon cycling,
      hypothesize likely effects and identify critical knowledge gaps for future carbon
      research. 

PMID- 24132940
TI  - Ketimido metallophthalocyanines: an approach to phthalocyanine-supported
      mononuclear high-valent ruthenium complexes.
AB  - A "metal-ketimine+ArI(OR)2 " approach has been developed for preparing metal
      ketimido complexes, and ketimido ligands are found to stabilize high-valent
      metallophthalocyanine (M-Pc) complexes such as ruthenium(IV) phthalocyanines.
      Treatment of bis(ketimine) ruthenium(II) phthalocyanines [Ru(II)(Pc)(HN=CPh2)2]
      (1 a) and [Ru(II) (Pc)(HNQu)2 ] (1b; HNQu=N-phenyl-1,4-benzoquinonediimine) with
      PhI(OAc)2 affords bis(ketimido) ruthenium(IV) phthalocyanines
      [Ru(IV)(Pc)(N=CPh2)2] (2a) and [Ru(IV)(Pc)(NQu)2] (2b), respectively. X-ray
      crystal structures of 1b and [Ru(II) (Pc)(PhN=CHPh)2] (1c) show Ru-N(ketimine)
      distances of 2.075(4) and 2.115(3) A, respectively. Complexes 2a,b readily revert
      to 1a,b upon treatment with phenols. (1)H NMR spectroscopy reveals that 2a,b are
      diamagnetic and 2b exists as two isomers, consistent with a proposed eclipsed
      orientation of the ketimido ligands in these ruthenium(IV) complexes. The
      reaction of 1a,b with PhI(OAc)2 to afford 2a,b suggests the utility of ArI(OR)2
      as an oxidative deprotonation agent for the generation of high-valent metal
      complexes featuring M-N bonds with multiple bonding characters. DFT and time
      dependent (TD)-DFT calculations have been performed on the electronic structures
      and the UV/Vis absorption spectra of 1b and 2b, which provide support for the
      diamagnetic nature of 2b and reveal a significant barrier for rotation of the
      ketimido group about the Ru-N(ketimido) bond.

PMID- 24132941
TI  - A quantitative method for measuring innate phagocytosis by human monocytes using
      real-time flow cytometry.
AB  - Phagocytosis is central to immunity however a rapid and standardized method is
      much needed for quantitative assessment of the phagocytic process. We describe a
      real-time flow cytometric method to quantitate the phagocytosis of fluorescent
      latex beads by human monocytes in serum-free conditions. Effects of buffer
      composition, temperature, pH, and bead surface on phagocytic rate are described.
      The innate phagocytic ability of human monocytes from single subjects measured by
      this method was relatively stable over many months although phagocytosis rate
      varied as much as two-fold between individuals. Comparable results were obtained
      with a simplified method using several mL of whole blood which is suitable for
      routine clinical application. This method also allows two-color flow cytometric
      measurement of cytosolic calcium levels during the phagocytic uptake of
      fluorescent beads.

PMID- 24132942
TI  - Capacitive epidermal electronics for electrically safe, long-term
      electrophysiological measurements.
AB  - Integration of capacitive sensing capabilities to epidermal electronic systems
      (EES) can enhance the robustness in operation for electrophysiological signal
      measurement. Capacitive EES designs are reusable, electrically safe, and
      minimally sensitive to motion artifacts. Experiments on human subjects illustrate
      levels of fidelity in ECG, EMG, and EOG recordings comparable to those of
      standard gel electrodes and of direct contact EES electrodes.

PMID- 24132943
TI  - Prognostic significance of metastasis-related microRNAs in early breast cancer
      patients with a long follow-up.
AB  - BACKGROUND: Stability of microRNAs (miRNAs) in formalin-fixed paraffin-embedded
      (FFPE) tissues enables their reliable analysis in archived FFPE tissue samples,
      which are an invaluable source for the evaluation of novel biomarkers. Especially
      in breast cancer, for which late relapses occur in many cases, analysis of miRNAs
      in FFPE tissues holds great potential, because it can lead to the discovery of
      novel biomarkers suitable for future routine clinical diagnostics for breast
      cancer. We investigated the prognostic significance of 6 metastasis-related
      miRNAs that can critically regulate various stages of migration and invasion and
      play critical roles in the multistep metastatic process. METHODS: We quantified
      the expression of 6 mature miRNAs (namely miR-21, miR-205, miR-10b, miR-210, miR
      335, and let-7a) by reverse-transcription quantitative PCR in FFPE tissues of 84
      patients with early breast cancer and a long follow-up and 13 cancer-free breast
      tissue FFPE samples that were used as the control group. We further correlated
      individual miRNA over- or underexpression with the disease-free interval (DFI)
      and overall survival (OS). RESULTS: Univariate analysis revealed that both miR-21
      and miR-205 were significantly associated with DFI and only miR-205 with OS.
      Multivariate analysis demonstrated that miR-205 and miR-21 were independent
      factors associated with early disease relapse, whereas only miR-205
      overexpression was associated with OS. CONCLUSIONS: Our results clearly indicate
      that deregulation of metastasis-associated miRNAs in primary tumors is associated
      with clinical outcome in patients with early breast cancer and can differentiate
      patients with higher risk in well-characterized subgroups.

PMID- 24132944
TI  - Flexible micro spring array device for high-throughput enrichment of viable
      circulating tumor cells.
AB  - BACKGROUND: The dissemination of circulating tumor cells (CTCs) that cause
      metastases in distant organs accounts for the majority of cancer-related deaths.
      CTCs have been established as a cancer biomarker of known prognostic value. The
      enrichment of viable CTCs for ex vivo analysis could further improve cancer
      diagnosis and guide treatment selection. We designed a new flexible micro spring
      array (FMSA) device for the enrichment of viable CTCs independent of antigen
      expression. METHODS: Unlike previous microfiltration devices, flexible structures
      at the micro scale minimize cell damage to preserve viability, while maximizing
      throughput to allow rapid enrichment directly from whole blood with no need for
      sample preprocessing. Device performance with respect to capture efficiency,
      enrichment against leukocytes, viability, and proliferability was characterized.
      CTCs and CTC microclusters were enriched from clinical samples obtained from
      breast, lung, and colorectal cancer patients. RESULTS: The FMSA device enriched
      tumor cells with 90% capture efficiency, higher than 10(4) enrichment, and better
      than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm(2)
      device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples
      (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the
      commercial CellSearch(r) system. There was no incidence of clogging in over 100
      tested fresh whole blood samples. CONCLUSIONS: The FMSA device provides a
      versatile platform capable of viable enrichment and analysis of CTCs from
      clinically relevant volumes of whole blood.

PMID- 24132945
TI  - Effectiveness of written hospitalist sign-outs in answering overnight inquiries.
AB  - BACKGROUND: Hospitalists are key providers of care to medical inpatients, and
      sign-out is an integral part of providing safe, high-quality inpatient care.
      There is little known about hospitalist-to-hospitalist sign-out. OBJECTIVE: To
      evaluate the quality of hospitalist/physician-extender sign-outs by assessing how
      well the sign-out prepares the night team for overnight events and to determine
      attributes of effective sign-out. DESIGN: Analysis of a written-only sign-out
      protocol on a nonteaching hospitalist service using prospective data collected by
      an attending physician survey during overnight shifts. SETTING: Yale-New Haven
      Hospital, a 966-bed, urban, academic medical center in New Haven, Connecticut
      with approximately 13,700 hospitalist discharges annually. RESULTS: We recorded
      124 inquiries about 96 patients during 6 days of data collection in 2012.
      Hospitalists referenced the sign-out for 89 (74%) inquiries, and the sign-out was
      considered sufficient in isolation to respond to 27 (30%) of these inquiries.
      Hospitalists physically saw the patient for 14 (12%) of inquiries. Nurses were
      the originator for most inquiries (102 [82%]). The most common inquiry topics
      were medications (55 [45%]), plan of care (26 [21%]), and clinical changes (26
      [21%]). Ninety-five (77%) inquiries were considered to be "somewhat" or "very"
      clinically important by the hospitalist. CONCLUSIONS: Overall, we found that
      attending hospitalists rely heavily on written sign-out to address overnight
      inquiries, but that those sign-outs are not reliably effective. Future work to
      better understand the roles of written and verbal components in sign-out is
      needed to help improve the safety of overnight care.

PMID- 24132946
TI  - Early age-dependent impairments of context-dependent extinction learning, object
      recognition, and object-place learning occur in rats.
AB  - The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of
      memory depend on adequate hippocampal function. Extinction learning comprises
      active inhibition of no longer relevant learned information concurrent with
      suppression of a previously learned reaction. It is highly dependent on context,
      and evidence exists that it requires hippocampal activation. In this study, we
      addressed whether context-based extinction as well as hippocampus-dependent
      tasks, such as object recognition and object-place recognition, are equally
      affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar
      rats were used. For the extinction study, animals learned that a particular floor
      context indicated that they should turn into one specific arm (e.g., left) to
      receive a food reward. On the day after reaching the learning criterion of 80%
      correct choices, the floor context was changed, no reward was given and animals
      were expected to extinguish the learned response. Both, young and older rats
      managed this first extinction trial in the new context with older rats showing a
      faster extinction performance. One day later, animals were returned to the T-maze
      with the original floor context and renewal effects were assessed. In this case,
      only young but not older rats showed the expected renewal effect (lower
      extinction ratio as compared to the day before). To assess general memory
      abilities, animals were tested in the standard object recognition and object
      place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals.
      Object recognition memory was poor at short-term and intermediate time-points in
      older but not young rats. Object-place memory performance was unaffected at 5
      min, but impaired at 1 h in older but not young rats. Both groups were impaired
      at 7 days. These findings support that not only aspects of general memory, but
      also context-dependent extinction learning, are affected by moderate aging. This
      may reflect less flexibility in revising hard-wired knowledge or reduced
      adaptability to new learning challenges.

PMID- 24132947
TI  - Remote opto-acoustic probing of single-cell adhesion on metallic surfaces.
AB  - The reflection of picosecond ultrasonic pulses from a cell-substrate interface is
      used to probe cell-biomaterial adhesion with a subcell resolution. We culture
      monocytes on top of a thin biocompatible Ti metal film, supported by a
      transparent sapphire substrate. Low-energy femtosecond pump laser pulses are
      focused at the bottom of the Ti film to a micron spot. The subsequent ultrafast
      thermal expansion launches a longitudinal acoustic pulse in Ti, with a broad
      spectrum extending up to 100 GHz. We measure the acoustic echoes reflected from
      the Ti-cell interface through the transient optical reflectance changes. The time
      frequency analysis of the reflected acoustic pulses gives access to a map of the
      cell acoustic impedance Zc and to a map of the film-cell interfacial stiffness K
      simultaneously. Variations in Zc across the cell are attributed to rigidity and
      density fluctuations within the cell, whereas variations in K are related to
      interfacial intermolecular forces and to the nano-architecture of the
      transmembrane bonds.

PMID- 24132948
TI  - A noble-metal-free porous coordination framework with exceptional sensing
      efficiency for oxygen.

PMID- 24132949
TI  - Analysis of the shedding of three beta-herpesviruses in urine and saliva of
      children with renal disease.
AB  - Cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and 7 (HHV-7) are important
      pathogens in immunocompromised patients. To elucidate the kinetics of the three
      beta-herpesviruses in saliva and urine samples were collected serially from
      children with renal diseases. Twenty children with renal diseases were enrolled
      in this study. A total of 240 saliva and urine samples were collected monthly
      from the patients over a 1-year period. Viral DNAs loads were measured by real
      time PCR. In 10 CMV seropositive patients CMV DNA was detected rarely in saliva
      and CMV DNA load was lower than the other two beta-herpesviruses DNA loads. All
      patients were seropositive for HHV-6B and the virus was detected frequently in
      saliva. Two of 20 patients were HHV-7 seronegative. High copies of viral DNA were
      detected continuously in saliva of the HHV-7 seropositive patients. Although
      neither CMV nor HHV-6B DNA load was different among the three renal diseases, HHV
      7 DNA load was different among the diseases (P = 0.039). HHV-6B DNA loads were
      significantly higher in patients with immunosuppressive treatment compared to
      those without treatment (P = 0.013). Although CMV DNA was detected in urine
      samples collected from 5 of 10 CMV seropositive patients, HHV-6B and HHV-7 DNA
      were detected at relatively low frequencies in urine. No remarkable temporal
      associations between viral DNA excretion and proteinuria or immunosuppressive
      treatment were demonstrated. The pattern of viral DNA excretion in saliva and
      urine were different among the three viruses. No temporal correlation was
      observed between viral infection and renal diseases.

PMID- 24132950
TI  - The adult head morphology of the hessian fly Mayetiola destructor (Diptera,
      Cecidomyiidae).
AB  - Cover illustration. Mayetiola destructor is a major pest of wheat in Europe,
      North Africa and North America. In this issue of the Journal of Morphology,
      Schneeberg et al. (pp. 1299-1311) investigate the adult head structures of the
      cecidomyiid fly and compared their findings with evolutionarily less successful
      families within Bibionomorpha. The cover image shows a histological cross section
      of the head of Mayetiola destructor (Diptera, Cecidomyiidae). 

PMID- 24132954
TI  - Animal manure application and soil organic carbon stocks: a meta-analysis.
AB  - The impact of animal manure application on soil organic carbon (SOC) stock
      changes is of interest for both agronomic and environmental purposes. There is a
      specific need to quantify SOC change for use in national greenhouse gas (GHG)
      emission inventories. We quantified the response of SOC stocks to manure
      application from a large worldwide pool of individual studies and determined the
      impact of explanatory factors such as climate, soil properties, land use and
      manure characteristics. Our study is based on a meta-analysis of 42 research
      articles totaling 49 sites and 130 observations in the world. A dominant effect
      of cumulative manure-C input on SOC response was observed as this factor
      explained at least 53% of the variability in SOC stock differences compared to
      mineral fertilized or unfertilized reference treatments. However, the effects of
      other determining factors were not evident from our data set. From the linear
      regression relating cumulative C inputs and SOC stock difference, a global manure
      C retention coefficient of 12% +/- 4 (95% Confidence Interval, CI) could be
      estimated for an average study duration of 18 years. Following an approach
      comparable to the Intergovernmental Panel on Climate Change, we estimated a
      relative SOC change factor of 1.26 +/- 0.14 (95% CI) which was also related to
      cumulative manure-C input. Our results offer some scope for the refinement of
      manure retention coefficients used in crop management guidelines and for the
      improvement of SOC change factors for national GHG inventories by taking into
      account manure-C input. Finally, this study emphasizes the need to further
      document the long-term impact of manure characteristics such as animal species,
      especially pig and poultry, and manure management systems, in particular liquid
      vs. solid storage.

PMID- 24132955
TI  - Self-efficacy in diabetic care and occurrence of adverse events in an ambulatory
      setting.
AB  - OBJECTIVE: To assess the relationship between patients' self-efficacy and the
      occurrence of adverse events in patients with insulin-using, type-2 diabetes
      mellitus in an ambulatory setting. DESIGN: A prospective cohort study. Patients'
      risks were estimated by relative risk (RR) and analyzed by Poisson regression
      using the generalized estimating equation (GEE). SETTING: Diabetic clinic at a
      university-affiliated, tertiary-care hospital in Bangkok, Thailand. PARTICIPANTS:
      One hundred and fifty-seven patients in the low self-efficacy group and 153
      patients in the high self-efficacy group based on their pre-test scores,
      including self-efficacy in problem-solving and daily living. MAIN OUTCOME
      MEASURES: Adverse events defined as unplanned incidents related to medical
      management in diabetic care, leading to patient harm. Patient data were followed
      up every 3 months for 1 year. RESULTS: The incident rate of adverse events in the
      low self-efficacy group was 2.12 incidents per 100 person-months, in comparison
      with 0.44 incidents per 100 person-months in the high self-efficacy group,
      resulting in adjusted RR of 4.75 (95% confidence interval (CI): 2.19-10.28). The
      use of long-acting insulin was also found to increase the risk of adverse events
      by 3.11 times (95% CI: 1.35-7.18) without interaction with patients' self
      efficacies. CONCLUSION: To increase patients' self-efficacy by strengthening
      patient and family involvement may help prevent harmful events and improve
      patient safety in an ambulatory setting among chronically ill patients with type
      2 diabetes mellitus.

PMID- 24132956
TI  - Impact of electronic chemotherapy order forms on prescribing errors at an urban
      medical center: results from an interrupted time-series analysis.
AB  - OBJECTIVE: To evaluate the impact of electronic standardized chemotherapy
      templates on incidence and types of prescribing errors. DESIGN: A quasi
      experimental interrupted time series with segmented regression. SETTING: A 700
      bed multidisciplinary tertiary care hospital with an ambulatory cancer center.
      PARTICIPANTS: A multidisciplinary team including oncology physicians, nurses,
      pharmacists and information technologists. INTERVENTION(S): Standardized, regimen
      specific, chemotherapy prescribing forms were developed and implemented over a 32
      month period. MAIN OUTCOME MEASURE(S): Trend of monthly prevented prescribing
      errors per 1000 chemotherapy doses during the pre-implementation phase (30
      months), immediate change in the error rate from pre-implementation to
      implementation and trend of errors during the implementation phase. Errors were
      analyzed according to their types: errors in communication or transcription,
      errors in dosing calculation and errors in regimen frequency or treatment
      duration. Relative risk (RR) of errors in the post-implementation phase (28
      months) compared with the pre-implementation phase was computed with 95%
      confidence interval (CI). RESULTS: Baseline monthly error rate was stable with
      16.7 prevented errors per 1000 chemotherapy doses. A 30% reduction in prescribing
      errors was observed with initiating the intervention. With implementation, a
      negative change in the slope of prescribing errors was observed (coefficient = 
      0.338; 95% CI: -0.612 to -0.064). The estimated RR of transcription errors was
      0.74; 95% CI (0.59-0.92). The estimated RR of dosing calculation errors was 0.06;
      95% CI (0.03-0.10). The estimated RR of chemotherapy frequency/duration errors
      was 0.51; 95% CI (0.42-0.62). CONCLUSIONS: Implementing standardized chemotherapy
      prescribing templates significantly reduced all types of prescribing errors and
      improved chemotherapy safety.

PMID- 24132957
TI  - Mentoring of physicians at a community-based health system: preliminary findings.
AB  - BACKGROUND: Mentoring has been suggested as 1 way to reduce physician stress and
      improve professional satisfaction, yet mentoring programs for physicians have
      focused principally on faculties of academic medical centers. Recently, a formal
      mentoring program for physicians in full-time clinical practice was created at a
      regional health system in western Connecticut. We describe the results of a
      survey of mentees' impressions of the program after its first year. METHODS: We
      surveyed hospitalists and other physicians who had participated in the mentoring
      program to determine their reasons for participation, whether the program was
      helpful (and if so in what ways), and their recommendations for improvement.
      RESULTS: Twenty-seven of the 39 participants responded to the survey (69%).
      Hospitalists were the most likely to participate in the mentoring program (18 of
      24) and to respond to the survey. Career planning (52%), balance among personal
      and professional life (43%), and leadership development (38%) were the most
      common reasons given for meeting with a mentor. All but 1 respondent felt the
      mentoring program met their expectations by setting goals (62%), planning next
      steps in their career(60%), and gaining new insights (52%). CONCLUSIONS:
      Community-based health systems that seek to improve the professional satisfaction
      of their physicians should be interested in this description of the physician
      mentoring program of the Western Connecticut Health Network.

PMID- 24132958
TI  - Sex, drugs, and adult neurogenesis: sex-dependent effects of escalating
      adolescent cannabinoid exposure on adult hippocampal neurogenesis, stress
      reactivity, and amphetamine sensitization.
AB  - Cannabinoid exposure during adolescence has adverse effects on neuroplasticity,
      emotional behavior, cognition, and reward sensitivity in adult rats. We
      investigated whether escalating doses of the cannabinoid receptor 1 (CB1 R)
      agonist, HU-210, in adolescence would affect adult hippocampal neurogenesis and
      behavioral processes putatively modulated by hippocampal neurogenesis, in adult
      male and female Sprague-Dawley rats. Escalating doses of HU-210 (25, 50, and 100
      ug/kg), or vehicle were administered from postnatal day (PND) 35 to 46. Animals
      were left undisturbed until PND 70, when they were treated with 5-bromo-2
      deoxyuridine (BrdU; 200 mg/kg) and perfused 21 days later to examine density of
      BrdU-ir and BrdU/NeuN cells in the dentate gyrus. In another cohort, hypothalamic
      pituitary-adrenal (HPA) axis reactivity to an acute restraint stress (30 min; PND
      75) and behavioral sensitization to d-amphetamine sulfate (1-2 mg/kg; PND 105
      134) were assessed in adulthood. Adolescent HU-210 administration suppressed the
      density of BrdU-ir cells in the dentate gyrus in adult male, but not adult female
      rats. Adolescent HU-210 administration also induced significantly higher peak
      corticosterone levels and reminiscent of the changes in neurogenesis, this effect
      was more pronounced in adult males than females. However, adolescent cannabinoid
      treatment resulted in significantly higher stereotypy scores in adult female, but
      not male, rats. Thus, adolescent CB1 R activation suppressed hippocampal
      neurogenesis and increased stress responsivity in adult males, but not females,
      and enhanced amphetamine sensitization in adult female, but not male, rats. Taken
      together, increased CB1 R activation during adolescence results in sex-dependent,
      long-term, changes to hippocampal structure and function, an effect that may shed
      light on differing vulnerabilities to developing disorders following adolescent
      cannabinoid exposure, based on sex.

PMID- 24132959
TI  - Involvement of DOT1L in the remodeling of heterochromatin configuration during
      early preimplantation development in mice.
AB  - The global chromatin configuration is dramatically remodeled during fertilization
      and early preimplantation development. Although the chromocenters, which are
      pericentromeric heterochromatin clusters, are observed in the nuclei of oocytes,
      they disappear after fertilization and then reappear at the four-cell stage. To
      elucidate the mechanism of this reorganization of heterochromatin, we
      investigated the expression and nuclear localization of DOT1L, which is involved
      in the regulation of heterochromatin structure through histone H3 lysine 79
      (H3K79) methyltransferase activity, during preimplantation development. The Dot1L
      mRNA level was low at the two-cell stage. In the analysis by the
      immunocytochemistry, DOT1L protein was not observed in the nuclei at this stage.
      Microinjection of Flag-tagged Dot1L cRNA revealed that the DOT1L protein was
      localized in the nucleus of the embryos at the one-cell and four-cell stages but
      not at the two-cell stage. However, C-terminus-truncated DOT1L was localized in
      the nucleus of two-cell-stage embryos. Expression of the truncated DOT1L caused
      hypermethylation on H3K79 and the formation of chromocenter-like structures at
      the two-cell stage. Intriguingly, the expression of catalytically inactive
      truncated DOT1L also caused the formation of chromocenter-like structures without
      an increase in H3K79 methylation. Most embryos expressing the truncated DOT1L or
      its inactive form were arrested at the two-cell stage. These results suggest that
      the absence of DOT1L, which is involved in the formation of a specific
      configuration of heterochromatin at the two-cell stage, is essential for early
      preimplantation development. 

PMID- 24132960
TI  - Regulation of baboon fetal ovarian development by placental estrogen: onset of
      puberty is delayed in offspring deprived of estrogen in utero.
AB  - Using the baboon as a model for studies of human reproductive biology, we
      previously showed that placental estrogen regulates fetal ovarian follicle
      development. In this study, offspring of baboons untreated or treated in utero
      with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and
      estradiol were reared to adulthood to determine whether estrogen programming of
      the fetal ovary impacted puberty and reproduction in adulthood. All offspring
      exhibited normal growth and blood pressure/chemistries. Puberty onset in
      untreated baboons (43.2 +/- 1.4 mo) was delayed (P < 0.01) in animals of
      letrozole-treated mothers (49.0 +/- 1.2 mo) and normal in offspring of mothers
      treated with letrozole and estradiol (42.7 +/- 0.8 mo). During the first 2 yr
      postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 +/- 1.3 days)
      were longer (P < 0.05) than in untreated baboons (38.3 +/- 0.5 days) or those
      treated with letrozole and estrogen (39.6 +/- 0.8 days). Moreover, in estrogen
      suppressed offspring, serum levels of estradiol were lower and follicle
      stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and
      the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty
      onset was delayed and menstrual cycles prolonged and associated with altered
      serum hormone levels in baboon offspring that developed in an intrauterine
      environment in which estradiol levels were suppressed. Because puberty and
      follicle development, as shown previously, were normal in baboons treated in
      utero with letrozole and estradiol, we propose that fetal ovarian development and
      timely onset of puberty in the primate is programmed by fetal exposure to
      placental estrogen. 

PMID- 24132961
TI  - YES1 activation elicited by heat stress is anti-apoptotic in mouse pachytene
      spermatocytes.
AB  - Deregulated expression of protein tyrosine phosphorylation has been implicated in
      testicular response to different stimuli. Herein, YES1, a nonreceptor protein
      tyrosine kinase, was found to be significantly up-regulated in pachytene
      spermatocytes (PS) during early recovery from a transient testicular heat stress.
      Coculture of PS with Sertoli cells (SCs) could enhance the hyperthermia-induced
      YES1 activation, indicative of a positive regulation of the paracrine signaling.
      Moreover, SU6656, a selective YES1 inhibitor, was shown to effectively block YES1
      activity, thereafter resulting in a dramatic increase of heat stress-induced
      apoptosis in primary cultured PS. Mechanistically, the antiapoptotic effect of
      YES1 activation in response to testicular heat insult may mediate via the
      regulation of extracellular signal-regulated kinase (ERK)/metastasis-associated 1
      (MTA1) cascade. From a clinical standpoint, a notably higher level of YES1
      expression was observed in the pathological testis from varicocele patients as
      compared to a negligible staining in the control group. Taken together, our
      present results provide the first evidence that the YES1/ERK/MTA1/p53 cascade may
      serve as a naturally occurring, indispensable self-defensive mechanism
      maintaining apoptotic balance during meiotic heat stress. Our study may have also
      partially answered the question of how activation of signal pathways at the cell
      membrane surface interacts with the key regulatory events occurring in the
      nucleus during testicular heat shock. 

PMID- 24132962
TI  - Stroke prevention in older adults with atrial fibrillation.

PMID- 24132963
TI  - Psychoanalysis and APsaA in the twenty-first century: their fates may be
      different.

PMID- 24132964
TI  - A patient returns: editors' introduction.

PMID- 24132965
TI  - Introduction: a patient returns.

PMID- 24132966
TI  - A patient returns.

PMID- 24132967
TI  - The effect of postanalytic contact.

PMID- 24132968
TI  - Varieties of psychoanalytic experience: lessons from returning patients.

PMID- 24132969
TI  - A patient returns: discussion.

PMID- 24132970
TI  - Response to Zepf and Gerlach.

PMID- 24132971
TI  - Safety for the analysand, safety for the analyst, safety for the dyad.

PMID- 24132974
TI  - Fasting insulin concentrations and incidence of hypertension, stroke, and
      coronary heart disease: a meta-analysis of prospective cohort studies.
AB  - BACKGROUND: Insulin resistance is a precursor of numerous chronic diseases,
      including cardiovascular disease (CVD). The fasting insulin concentration is
      considered a reasonable surrogate of insulin resistance, especially among
      nondiabetic individuals. OBJECTIVE: We aimed to quantitatively summarize the
      literature on the association of fasting insulin concentrations with risk of
      hypertension, stroke, and coronary heart disease (CHD) by conducting a meta
      analysis of prospective cohort studies. DESIGN: Eligible studies were identified
      by searching PubMed and EMBASE through January 2013. Additional information was
      retrieved through Google Scholar or a hand review of the reference lists from
      relevant articles. Prospective cohort studies that reported RRs and corresponding
      95% CIs for the association of interest were identified. Data were extracted
      independently by 2 investigators, and the weighted RRs and 95% CIs for the
      associations were obtained by using a random-effects model. RESULTS: Of the 22
      identified studies, 10 reported results on hypertension (36,617 individuals and
      4491 cases), 7 on stroke (27,887 individuals and 1550 cases), and 9 on CHD
      (22,379 individuals and 1986 cases). Comparison of the highest with the lowest
      quantile of fasting insulin concentrations showed a pooled RR (95% CI) of 1.63
      (1.35, 1.97) for hypertension, 1.18 (0.87, 1.60) for stroke, and 1.50 (1.28,
      1.77) for CHD. Each 50-pmol/L increment in fasting insulin was associated with a
      25% increase in risk of hypertension [RR: 1.25 (1.14, 1.36)] and a 16% increase
      in risk of CHD [RR: 1.16 (1.10, 1.22)] but was not associated with risk of stroke
      [RR: 0.999 (0.99, 1.01)]. CONCLUSIONS: A higher fasting insulin concentration or
      hyperinsulinemia was significantly associated with an increased risk of
      hypertension and CHD but not stroke. This meta-analysis suggests that early
      fasting insulin ascertainment in the general population may help clinicians
      identify those who are potentially at high risk of CVD.

PMID- 24132975
TI  - Pregnancy alters choline dynamics: results of a randomized trial using stable
      isotope methodology in pregnant and nonpregnant women.
AB  - BACKGROUND: Although biomarkers of choline metabolism are altered by pregnancy,
      little is known about the influence of human pregnancy on the dynamics of choline
      related metabolic processes. OBJECTIVE: This study used stable isotope
      methodology to examine the effects of pregnancy on choline partitioning and the
      metabolic activity of choline-related pathways. DESIGN: Healthy third-trimester
      pregnant (n = 26; initially week 27 of gestation) and nonpregnant (n = 21) women
      consumed 22% of their total choline intake (480 or 930 mg/d) as methyl-d9-choline
      for the final 6 wk of a 12-wk feeding study. RESULTS: Plasma d9-betaine:d9
      phosphatidylcholine (PC) was lower (P <= 0.04) in pregnant than in nonpregnant
      women, suggesting greater partitioning of choline into the cytidine diphosphate
      choline (CDP-choline) PC biosynthetic pathway relative to betaine synthesis
      during pregnancy. Pregnant women also used more choline-derived methyl groups for
      PC synthesis via phosphatidylethanolamine N-methyltransferase (PEMT) as indicated
      by comparable increases in PEMT-PC enrichment in pregnant and nonpregnant women
      despite unequal (pregnant > nonpregnant; P < 0.001) PC pool sizes. Pregnancy
      enhanced the hydrolysis of PEMT-PC to free choline as shown by greater (P <
      0.001) plasma d3-choline:d3-PC. Notably, d3-PC enrichment increased (P <= 0.011)
      incrementally from maternal to placental to fetal compartments, signifying the
      selective transfer of PEMT-PC to the fetus. CONCLUSIONS: The enhanced use of
      choline for PC production via both the CDP-choline and PEMT pathways shows the
      substantial demand for choline during late pregnancy. Selective partitioning of
      PEMT-PC to the fetal compartment may imply a unique requirement of PEMT-PC by the
      developing fetus.

PMID- 24132976
TI  - Effects of vitamin D supplementation on glucose metabolism, lipid concentrations,
      inflammation, and oxidative stress in gestational diabetes: a double-blind
      randomized controlled clinical trial.
AB  - BACKGROUND: To our knowledge, there is no study that has examined the effects of
      vitamin D supplementation on metabolic status in gestational diabetes mellitus
      (GDM). OBJECTIVE: This study was designed to assess the effects of vitamin D
      supplementation on metabolic profiles, high-sensitivity C-reactive protein, and
      biomarkers of oxidative stress in pregnant women with GDM. DESIGN: This
      randomized, double-blind, placebo-controlled clinical trial was conducted in 54
      women with GDM. Subjects were randomly assigned to receive either vitamin D
      supplements or placebo. Individuals in the vitamin D group (n = 27) received
      capsules containing 50,000 IU vitamin D3 2 times during the study (at baseline
      and at day 21 of the intervention) and those in the placebo group (n = 27)
      received 2 placebos at the same times. Fasting blood samples were collected at
      baseline and after 6 wk of the intervention to quantify relevant variables.
      RESULTS: Cholecalciferol supplementation resulted in increased serum 25
      hydroxyvitamin D concentrations compared with placebo (+18.5 +/- 20.4 compared
      with +0.5 +/- 6.1 ng/mL; P < 0.001). Furthermore, intake of vitamin D supplements
      led to a significant decrease in concentrations of fasting plasma glucose (-17.1
      +/- 14.8 compared with -0.9 +/- 16.6 mg/dL; P < 0.001) and serum insulin (-3.08
      +/- 6.62 compared with +1.34 +/- 6.51 MUIU/mL; P = 0.01) and homeostasis model of
      assessment-insulin resistance (-1.28 +/- 1.41 compared with +0.34 +/- 1.79; P <
      0.001) and a significant increase in the Quantitative Insulin Sensitivity Check
      Index (+0.03 +/- 0.03 compared with -0.001 +/- 0.02; P = 0.003) compared with
      placebo. A significant reduction in concentrations of total (-11.0 +/- 23.5
      compared with +9.5 +/- 36.5 mg/dL; P = 0.01) and low-density lipoprotein (LDL) (
      10.8 +/- 22.4 compared with +10.4 +/- 28.0 mg/dL; P = 0.003) cholesterol was also
      seen after vitamin D supplementation. CONCLUSIONS: Vitamin D supplementation in
      pregnant women with GDM had beneficial effects on glycemia and total and LDL
      cholesterol concentrations but did not affect inflammation and oxidative stress.
      This trial was registered at www.irct.ir as IRCT201305115623N7.

PMID- 24132977
TI  - Zinc for preterm infants: Who needs it and how much is needed?

PMID- 24132978
TI  - Post-1000 days growth trajectories and child cognitive development in low- and
      middle-income countries.

PMID- 24132979
TI  - Supplemental feeding during pregnancy compared with maternal supplementation
      during lactation does not affect schooling and cognitive development through late
      adolescence.
AB  - BACKGROUND: The long-term impact of early malnutrition on human capital outcomes
      remains unclear, and existing evidence has come largely from observational
      studies. OBJECTIVE: We compared the impact of a nutritional supplement given
      during pregnancy or lactation in rural Gambia on educational performance and
      cognitive ability in offspring at their maturity. DESIGN: This study was a follow
      up of a randomized trial of prenatal high protein and energy supplementation
      conducted between 1989 and 1994. Subjects were 16-22 y of age at follow-up, and
      information was collected on schooling achievement and cognitive ability by using
      the Raven's progressive matrices test, Mill Hill vocabulary test, and forward and
      backward digit-span tests. RESULTS: A total of 1459 individuals were traced and
      interviewed and represented 71% of the original cohort and 81% of the surviving
      cohort. There was no difference in cognitive ability or educational attainment
      between treatment groups by using any of the methods of assessment. CONCLUSION:
      We have shown little evidence to support a long-term effect of prenatal protein
      energy supplementation compared with supplementation during lactation on
      cognitive development in rural Gambians. This trial was registered at
      http://www.controlled-trials.com as ISRCTN72582014.

PMID- 24132981
TI  - Variable photophysical properties of phosphorescent iridium(III) complexes
      triggered by closo- and nido-carborane substitution.

PMID- 24132980
TI  - Relative ability of fat and sugar tastes to activate reward, gustatory, and
      somatosensory regions.
AB  - BACKGROUND: Although the intake of high-fat and high-sugar food activates
      mesolimbic reward, gustatory, and oral somatosensory brain regions, contributing
      to overeating, few studies have examined the relative role of fat and sugar in
      the activation of these brain regions, which would inform policy, prevention, and
      treatment interventions designed to reduce obesity. OBJECTIVE: We evaluated the
      effect of a high-fat or high-sugar equicaloric chocolate milkshake and increasing
      fat or sugar milkshake content on the activation of these regions. DESIGN:
      Functional magnetic resonance imaging was used to assess the neural response to
      the intake of high-fat/high-sugar, high-fat/low-sugar, low-fat/high-sugar, and
      low-fat/low-sugar chocolate milkshakes and a tasteless solution in 106 lean
      adolescents (mean +/- SD age = 15.00 +/- 0.88 y). Analyses contrasted the
      activation to the various milkshakes. RESULTS: High-fat compared with high-sugar
      equicaloric milkshakes caused greater activation in the bilateral caudate,
      postcentral gyrus, hippocampus, and inferior frontal gyrus. High-sugar compared
      with high-fat equicaloric milkshakes caused greater activation in the bilateral
      insula extending into the putamen, the Rolandic operculum, and thalamus, which
      produced large activation regions. Increasing sugar in low-fat milkshakes caused
      greater activation in the bilateral insula and Rolandic operculum; increasing fat
      content did not elicit greater activation in any region. CONCLUSIONS: Fat caused
      greater activation of the caudate and oral somatosensory regions than did sugar,
      sugar caused greater activation in the putamen and gustatory regions than did
      fat, increasing sugar caused greater activity in gustatory regions, and
      increasing fat did not affect the activation. Results imply that sugar more
      effectively recruits reward and gustatory regions, suggesting that policy,
      prevention, and treatment interventions should prioritize reductions in sugar
      intake. This trial was registered at clinicaltrials.gov as DK092468.

PMID- 24132982
TI  - Urinary incontinence 4 and 12 years after first delivery: risk factors associated
      with prevalence, incidence, remission, and persistence in a cohort of 236 women.
AB  - AIMS: Our aim was to study risk factors associated with prevalence, incidence,
      and remission of UI 4 and 12 years after first delivery. METHODS: Seven hundred
      seventy-four nulliparous women who gave birth in 1996 in two French maternity
      units at term received a questionnaire about their urinary symptoms in 2000 and
      again in 2008. Two hundred thirty-six women returned a questionnaire about UI 4
      and 12 years after first delivery. Four groups of women were built: (A) women
      continent 4 and 12 years after first delivery; (B) women continent at 4 and
      incontinent at 12 years; (C) women incontinent at 4 and continent at 12 years;
      and (D) women incontinent at 4 and 12 years. Multivariate logistic regressions
      were used to determine risk factors of UI prevalence (groups B + D vs. A + C),
      incidence (B vs. A), remission (C vs. D), and onset of UI (D vs. B) RESULTS:
      Factors associated with UI 12 years after first pregnancy were: BMI (OR = 1.17
      [95%CI: 1.04-1.32], by 1 kg/m(2) ) and increasing BMI (1.43 [1.19-1.73]), first
      child's weight (1.08 [1.001-1.16], by 100 g) and UI during first pregnancy (3.77
      [1.83-7.76]). Factors associated with UI incidence were age at first delivery
      (0.86 [0.75-0.98]) and high BMI (1.24 [1.05-1.45]). Increasing BMI, UI during
      first pregnancy, and heavy first child reduce the likelihood of UI remission
      (0.37 [0.20-0.68], 0.11 [0.02-0.63], and 0.73[0.59-0.91], respectively).
      CONCLUSIONS: UI during first pregnancy could be indicative of individual
      susceptibility to UI. Obesity appears to be a modifiable factor for remission of
      UI in women.

PMID- 24132983
TI  - Long term recovery of median nerve repair using laser-activated chitosan adhesive
      films.
AB  - Sutures remain the standard peripheral nerve repair technique, whether applied
      directly or indirectly to nerve tissue. Unfortunately, significant postoperative
      complications can result, such as inflammation, neuroma formation and foreign
      body reactions. Photochemical-tissue-bonding (PTB) using rose Bengal (RB)
      integrated into a chitosan bioadhesive is an alternative nerve repair device that
      removes the need for sutures. Rats were arranged into three groups: RB-chitosan
      adhesives-repair, end-to-end epineural suture-repair (surgical standard) and sham
      laser-irradiated control. Groups were compared through histological assessment,
      electrophysiological recordings and grip motor strength. RB-chitosan adhesive
      repaired nerves displayed comparable results when compared to the standard suture
      repair based on histological and electrophysiological findings. Functionally, RB
      chitosan adhesive was associated with a quicker and more pronounced recovery of
      grip force when compared to the suture-repair.

PMID- 24132984
TI  - Microhabitats reduce animal's exposure to climate extremes.
AB  - Extreme weather events, such as unusually hot or dry conditions, can cause death
      by exceeding physiological limits, and so cause loss of population. Survival will
      depend on whether or not susceptible organisms can find refuges that buffer
      extreme conditions. Microhabitats offer different microclimates to those found
      within the wider ecosystem, but do these microhabitats effectively buffer extreme
      climate events relative to the physiological requirements of the animals that
      frequent them? We collected temperature data from four common microhabitats
      (soil, tree holes, epiphytes, and vegetation) located from the ground to canopy
      in primary rainforests in the Philippines. Ambient temperatures were monitored
      from outside of each microhabitat and from the upper forest canopy, which
      represent our macrohabitat controls. We measured the critical thermal maxima
      (CTmax ) of frog and lizard species, which are thermally sensitive and inhabit
      our microhabitats. Microhabitats reduced mean temperature by 1-2  degrees C and
      reduced the duration of extreme temperature exposure by 14-31 times. Microhabitat
      temperatures were below the CTmax of inhabitant frogs and lizards, whereas
      macrohabitats consistently contained lethal temperatures. Microhabitat
      temperatures increased by 0.11-0.66  degrees C for every 1  degrees C increase in
      macrohabitat temperature, and this nonuniformity in temperature change influenced
      our forecasts of vulnerability for animal communities under climate change.
      Assuming uniform increases of 6  degrees C, microhabitats decreased the
      vulnerability of communities by up to 32-fold, whereas under nonuniform increases
      of 0.66 to 3.96  degrees C, microhabitats decreased the vulnerability of
      communities by up to 108-fold. Microhabitats have extraordinary potential to
      buffer climate and likely reduce mortality during extreme climate events. These
      results suggest that predicted changes in distribution due to mortality and
      habitat shifts that are derived from macroclimatic samples and that assume
      uniform changes in microclimates relative to macroclimates may be overly
      pessimistic. Nevertheless, even nonuniform temperature increases within buffered
      microhabitats would still threaten frogs and lizards. 

PMID- 24132985
TI  - The poverty effects of a 'fat-tax' in Ireland.
AB  - To combat growing levels of obesity, health-related taxes have been suggested
      with taxes on foods high in fat or sugar. Such taxes have been criticised on the
      basis of their regressivity and potentially adverse impact upon poverty. This
      paper analyses the effect of such taxes on a range of poverty measures and also
      examines the effect of a revenue-neutral tax subsidy mixed with a tax on
      unhealthy food combined with a subsidy on more healthy food. Using Irish
      expenditure data, the results indicate that taxes on high fat/sugar goods on
      their own will be regressive but that a tax-subsidy combination can be broadly
      neutral with respect to poverty.

PMID- 24132986
TI  - Improved efficiency of reversed-phase carbon/nanodiamond/polymer core-shell
      particles for HPLC using carbonized poly(divinylbenzene) microspheres as the core
      materials.
AB  - Here, we report efficiencies up to 112,000 plates per meter (a reduced plate
      height, h, of 2.22) for RP, carbon/nanodiamond/aminopolymer particles using
      conventional injection conditions in HPLC. This efficiency greatly exceeds our
      best previously reported value of 71,000 N/m (h = 3.52). The carbon cores used in
      this study were derived from carbonized poly(divinylbenzene) spheres that were
      either made in-house by a two-step polymerization procedure or obtained
      commercially. The resulting particles showed good uniformity and were oxidized in
      nitric acid to increase their dispersability. X-ray photoelectron spectroscopy
      confirms particle oxidation and subsequent aminopolymer deposition. Layer-by
      layer (LbL) growth of poly(allyamine) and nanodiamond was demonstrated to produce
      core-shell particles. After LbL growth, the particles were functionalized,
      sieved, and packed into columns. The column functionalization and packing were
      reproducible. Van Deemter curves indicated that the commercially obtained
      poly(divinylbenzene) spheres outperformed those synthesized in our laboratory.
      The columns appear to be stable at 120 degrees C in a pH 11.3 mobile phase.
      Longer columns (2.1 * 50 mm) than previously reported were packed. Four essential
      oils were separated by gradient elution.

PMID- 24132988
TI  - Long-term outcomes of autologous pubovaginal fascia slings: is there a difference
      between primary and secondary slings?
AB  - INTRODUCTION: To report our long-term pubovaginal slings (PVS) outcomes between
      primary (PVS1) and secondary (PVS2) autologous fascia PVS, with the hypothesis
      that outcomes in PVS1 will be better than in PVS2. MATERIALS AND METHODS: IRB
      approved retrospective study of women undergoing PVS between 1996 and 2011 with
      minimum 6 months follow-up. Data reviewed included demographics, questionnaires
      that is, UDI-6, IIQ-7, QOL, prior anti-incontinence procedure, associated
      repairs, urodynamic findings and repeat procedures. Primary outcome and surgical
      success defined by: (1) QOL <= 3, (2) UDI question 3 on SUI <= 1, and (3) no SUI
      re-treatment/operation. Secondary outcomes included all other patient reported
      outcome measures (PROM). RESULTS: Of 110 patients, 84 had follow-up. Mean age was
      61 years (38-88) and median follow-up was 89 months (7-189). Demographic findings
      and type of fascia used were similar between the two groups. Mean postoperative
      scores were not statistically significant for total UDI-6 score (P = 0.62), IIQ-7
      (P = 0.30) and QOL (P = 0.35) between groups, but was statistically significant
      compared to baseline (P = 0.001) as expected. Twelve patients, 3 in PVS1 and 9 in
      PVS2 underwent subsequent procedures. Surgical success rate was 76% in PVS1 and
      52% in PVS2 for those with completed questionnaires. Overall, 78% (28) in PVS1
      and 69% (33) in PVS 2 required no further surgical intervention at last follow
      up. CONCLUSION: At long-term follow-up of average 7.4 years, primary and
      secondary PVS patients had comparable favourable functional outcomes with low
      morbidity. However, secondary PVS patients had lower success rates as per our
      definition with higher rate of additional procedures.

PMID- 24132991
TI  - Effects of the Good Behavior Game on classwide off-task behavior in a high school
      basic algebra resource classroom.
AB  - This study investigated the effects of the Good Behavior Game (GBG) on classwide
      off-task behavior in two ninth-grade basic algebra resource classes. Ten students
      with a variety of disabilities, in two classrooms, and their special education
      resource teacher participated in this study. A reversal design was employed, in
      which the special education teacher implemented GBG compared to typical practice
      algebra readiness instruction. Results showed that classwide off-task behavior
      decreased in the GBG conditions compared to the baseline and reversal conditions.
      Fidelity measures indicated that the teacher implemented GBG with fidelity.
      Students and the teacher rated GBG favorably. Overall findings support the use of
      GBG for reducing classwide off-task behavior. Implications for practice and
      future research directions are presented. 

PMID- 24132992
TI  - Characterization of broad-spectrum Mycobacterium abscessus class A beta
      lactamase.
AB  - OBJECTIVES: Imipenem and cefoxitin are used to treat Mycobacterium abscessus
      infections and have moderate activity against this fast-growing mycobacterium
      (MIC50 of 16 and 32 mg/L, respectively). M. abscessus is highly resistant to most
      other beta-lactams, although the underlying mechanisms have not been explored.
      Here, we characterized M. abscessus class A beta-lactamase (Bla(Mab)) and
      investigated its role in beta-lactam resistance. METHODS: Hydrolysis kinetic
      parameters of purified Bla(Mab) were determined by spectrophotometry for various
      beta-lactams and compared with those of related BlaC from Mycobacterium
      tuberculosis. MICs of beta-lactams were determined for M. abscessus CIP104536 and
      for Escherichia coli producing Bla(Mab) and BlaC. RESULTS: Bla(Mab) had a broad
      hydrolysis spectrum, similar to that of BlaC, but with overall higher catalytic
      efficiencies, except for cefoxitin. As expected from its in vivo efficacy,
      cefoxitin was very slowly hydrolysed by Bla(Mab) (k(cat)/K(m) = 6.7 M(-1) s(-1)).
      Bla(Mab) hydrolysed imipenem more efficiently (k(cat)/K(m) = 3.0 * 10(4) M(-1) s(
      1)), indicating that the in vivo activity of this drug might be improved by
      combination with a beta-lactamase inhibitor. beta-Lactamase inhibitors
      clavulanate, tazobactam and sulbactam did not inhibit Bla(Mab). This enzyme
      efficiently hydrolysed clavulanate, in contrast to BlaC, which is irreversibly
      acylated by this inhibitor. Bla(Mab) and BlaC were functional in E. coli and the
      resistance profiles mediated by these enzymes were in agreement with the kinetic
      parameters. CONCLUSIONS: M. abscessus produces a clavulanate-insensitive broad
      spectrum beta-lactamase that limits the in vivo efficacy of beta-lactams.

PMID- 24132993
TI  - Improved protocols for vibrational spectroscopic analysis of body fluids.
AB  - The applications of vibrational spectroscopy to the examination of human blood
      serum are explored. Although FTIR spectra can be recorded in aqueous solutions at
      (gelatin) concentrations as low as 100 mg/L, the high-wavenumber region remains
      obscured by water absorption. Using Raman spectroscopy, high quality spectra of
      gelatine solutions as low as 10 mg/L can be achieved, also covering the high
      wavenumber regions. In human serum, spectral profiles are weak and partially
      obscured by water features. Dried deposits are shown to be physically and
      chemically inhomogeneous resulting in reduced measurement reproducibility.
      Concentration of the serum using commercially available centrifugal filter
      devices results in an improvement in the spectral intensity and quality.
      Additionally, in Raman spectroscopy, reduced background and significantly
      enhanced signal collection is achievable by measurement in an inverted geometry.
      The improved protocols for spectroscopic measurement of human serum are
      applicable to a range of bodily fluids and should accelerate potential clinical
      applications.

PMID- 24132994
TI  - The effect of hyaluronic acid on biofunctionality of gelatin-collagen intestine
      tissue engineering scaffolds.
AB  - The creation of engineered intestinal tissue has recently stimulated new
      endeavors with the ultimate goal of intestinal replacement for massive resections
      of bowel. In this context, we investigated the effect of hyaluronic acid (HA) on
      the physicochemical characteristics of gelatin-collagen scaffolds and its
      cytocompatibilty to the human intestinal epithelial Caco-2 cell line in vitro.
      Gelatin/collagen hybrid scaffolds with different concentrations of HA were
      prepared by solvent casting and freeze-drying techniques and subsequent chemical
      crosslinking by genipin. The morphologies of the scaffolds were characterized by
      scanning electron microscopy and Fourier transform infrared spectroscopy. In
      vitro tests were carried out in phosphate-buffered saline (PBS) solution to study
      the swelling ratio and the biostability of the scaffolds. It was found that the
      porous structure of the scaffolds could be tailored by further addition of HA.
      Moreover, both the swelling ratio and the degradation rate of the scaffold
      increased by addition of HA. A resazurin-based cell viability assay was employed
      to determine the viability and estimate the number of scaffold-adherent Caco-2
      cells. The assay indicated that the scaffolds were all cytocompatible. We
      concluded that addition of less than 15% HA to scaffolds with a composition of
      9:1 gelatin:collagen results only in incremental improvement in the structural
      characteristics and cytocompatibility of the gelatin-collagen scaffolds. However,
      the scaffolds with 25% HA exhibited remarkable enhancement in physicochemical
      characteristics of the scaffolds including cell viability, growth, and attachment
      as well as their physical structure.

PMID- 24132995
TI  - High risk for obstructive sleep apnea in relation to hypertension among southeast
      Asian young adults: role of obesity as an effect modifier.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been linked to hypertension among
      middle-aged and older adults in Western countries. Few studies have focused on
      young adults, especially those in Southeast Asian countries undergoing
      epidemiologic transitions and experiencing elevated noncommunicable disease
      burden. We investigated associations of high risk for OSA with hypertension among
      Asian young adults. METHODS: A total of 2,911 college students in Thailand
      participated in this study. The high risk for OSA was assessed using the Berlin
      Questionnaire. Blood pressure (BP) and anthropometric measurements were taken by
      trained research staff. Elevated BP and hypertension were defined as BP >= 120/80
      mm Hg and >= 140/90 mm Hg, respectively. Multivariable logistic regression models
      were fit to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of
      elevated BP and hypertension. Stratified analyses were conducted to examine
      whether observed associations varied by weight status. RESULTS: High risk for OSA
      was significantly associated with elevated BP (OR = 2.38; 95% CI = 1.68-3.39) and
      hypertension (OR = 2.55; 95% CI = 1.57-4.15) after adjustment for demographic and
      lifestyle factors. When body mass index was further controlled for, observed
      associations were greatly attenuated. The associations were only evident among
      overweight and obese students. CONCLUSIONS: The high risk for OSA among
      overweight and obese young adults is associated with elevated BP and
      hypertension. Enhanced efforts directed toward screening and diagnosing OSA and
      weight control among young adults could be one strategy for improving
      cardiovascular health.

PMID- 24132996
TI  - Forest floor vegetation response to nitrogen deposition in Europe.
AB  - Chronic nitrogen (N) deposition is a threat to biodiversity that results from the
      eutrophication of ecosystems. We studied long-term monitoring data from 28 forest
      sites with a total of 1,335 permanent forest floor vegetation plots from northern
      Fennoscandia to southern Italy to analyse temporal trends in vascular plant
      species cover and diversity. We found that the cover of plant species which
      prefer nutrient-poor soils (oligotrophic species) decreased the more the measured
      N deposition exceeded the empirical critical load (CL) for eutrophication effects
      (P = 0.002). Although species preferring nutrient-rich sites (eutrophic species)
      did not experience a significantly increase in cover (P = 0.440), in comparison
      to oligotrophic species they had a marginally higher proportion among new
      occurring species (P = 0.091). The observed gradual replacement of oligotrophic
      species by eutrophic species as a response to N deposition seems to be a general
      pattern, as it was consistent on the European scale. Contrary to species cover
      changes, neither the decrease in species richness nor of homogeneity correlated
      with nitrogen CL exceedance (ExCLemp N). We assume that the lack of diversity
      changes resulted from the restricted time period of our observations. Although
      existing habitat-specific empirical CL still hold some uncertainty, we exemplify
      that they are useful indicators for the sensitivity of forest floor vegetation to
      N deposition. 

PMID- 24132997
TI  - Effect of background derivatization on the signal enhancement of pesticide
      residues extracted from edible oils.
AB  - The effect of background derivatization on the signal enhancement of pesticide
      residues extracted from edible oil samples was studied by GC with negative
      chemical ionization MS. The analytes were extracted by a solvent extraction
      process, and the extract was subjected to rapid low-temperature fat
      precipitation. The residual fatty acids were silylated by derivatization with N,O
      bis(trimethylsilyl)trifluoroacetamide. The chromatograms obtained from the
      derivatized samples showed higher signal intensity and lower detection levels
      when compared to the direct analysis without derivatization. The sensitivity
      levels of the method are either better or comparable to that of previously
      reported methodologies. The LODs of the analyzed organochlorine,
      organophosphorus, and synthetic pyrethroid residues in sunflower, rice bran, and
      ground oil samples were in the range of 0.02-0.5 ng/g, and the LOQs were in the
      range of 0.1-2 ng/g. The intraday and interday accuracies were in the range of 81
      116% with RSDs less than 14%. The recoveries obtained were in the range of 53-89%
      with the RSD values less than 13% for all the studied pesticide residues.

PMID- 24133003
TI  - Electrochemical sizing of organic nanoparticles.
AB  - The size of organic nanoparticles (NPs) can be electrochemically determined by
      Faradaic charge transfer when nanoparticles strike an electrode. Indigo NPs were
      used as a model (see distribution of the NP diameter). This strategy could be
      used for monitoring the size of a wide range of organic nanoparticles. 

PMID- 24133004
TI  - Waveguide evanescent field scattering microscopy: bacterial biofilms and their
      sterilization response via UV irradiation.
AB  - Waveguide Evanescent Field Scattering (WEFS) microscopy is introduced as a new
      and simple tool for label-free, high contrast imaging of bacteria and bacteria
      sensors. Bacterial microcolonies and single bacteria were discriminated both by
      their bright field images and by their evanescent scattering intensity. By
      comparing bright field images with WEFS images, the proportion of planktonic:
      sessile (i.e., "floating": attached) bacteria were measured. Bacteria were
      irradiated with UV light, which limited their biofilm forming capability. A
      quantitative decrease in attachment of individual, sessile bacteria and in
      attached, microcolony occupied areas was easily determined within the apparent
      biofilms with increasing UV dose. WEFS microscopy is an ideal tool for providing
      rapid quantitative data on biofilm formation.

PMID- 24133005
TI  - Efficacy and safety of oxybutynin topical gel 3% in patients with urgency and/or
      mixed urinary incontinence: a randomized, double-blind, placebo-controlled study.
AB  - AIMS: To assess the efficacy and safety of oxybutynin transdermal gel 3% (OTG3%),
      with propylene glycol for enhanced skin permeation, in patients with urinary
      incontinence (UI). METHODS: In this phase 3 study, 626 patients >=18 years old
      with urgency and/or mixed UI symptoms and predominantly urgency UI for >=3 months
      were randomized 1:1:1 to receive 12 weeks of OTG3% 84 mg, OTG3% 56 mg, or placebo
      gel applied once daily to abdomen, inner/upper thigh, or upper arm/shoulder.
      Primary efficacy endpoint was change from baseline to Week 12 in weekly UI
      episodes recorded in 3-day bladder diaries. Results were compared using analysis
      of covariance. Adverse events (AEs) were monitored. RESULTS: Efficacy was
      assessed in 601 (intent-to-treat) and safety in 626 patients. At 12 weeks, OTG3%
      84 mg/day achieved significantly greater improvement versus placebo in weekly UI
      episodes (mean change from baseline: -20.4 vs. -18.1; P < 0.05(a)), daily urinary
      frequency (-2.6 vs. -1.9; P = 0.001(b)), and urinary void volume (32.7 vs. 9.8; P
      < 0.0001(b)). Dry mouth, the most common treatment-related AE, occurred more
      often with OTG3% 84 mg/day (26/214 [12.1%]) vs. placebo (10/202 [5.0%]) (P =
      0.028); 4 OTG3% patients withdrew because of dry mouth. Application site erythema
      occurred more often with OTG3% 84 mg/day (8/214 [3.7%]) versus placebo (2/202
      [1.0%]) (P = NS); 12 OTG patients withdrew because of skin irritation. No serious
      treatment-related AEs occurred. CONCLUSIONS: OTG3% 84 mg/day was well tolerated
      and effective in improving urge incontinence or mixed UI symptoms with a
      predominance of UI in adults with overactive bladder.

PMID- 24133006
TI  - Melt-electrospun polycaprolactone strontium-substituted bioactive glass scaffolds
      for bone regeneration.
AB  - Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue
      engineering owing to good structural properties and processability. Strontium
      substituted bioactive glass (SrBG) has the ability to promote osteogenesis and
      may be incorporated into scaffolds intended for bone repair. Here, we describe
      for the first time, the development of a PCL-SrBG composite scaffold
      incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the
      technique of melt electrospinning. We show that we are able to reproducibly
      manufacture composite scaffolds with an interconnected porous structure and,
      furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions
      present in the SrBG component were shown to dissolve into cell culture media and
      promoted precipitation of a calcium phosphate layer on the scaffold surface which
      in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1
      cells compared to PLC-only scaffolds. These results suggest that melt-electrospun
      PCL-SrBG composite scaffolds show potential to become effective bone graft
      substitutes.

PMID- 24133008
TI  - Sample conditions to avoid pH distortion in RP-LC.
AB  - Band deformations might take place for acids and bases in preparative
      applications and adsorption studies where it is necessary to use overloaded
      injections. In this study, we focus on how deformations can be prevented without
      using highly concentrated buffers that may precipitate in the eluent. We have
      systematically investigated how the elution zones depend on which protolytic form
      the analyte has when it is dissolved. Basic and acidic model compounds are
      investigated using eluents with different pH values and the resulting elution
      profiles are compared when the analytes are dissolved in their protonated and
      deprotonated form, i.e., in uncharged form or as different kinds of salts.
      Depending on the analyte's protolytic form, a sample zone is created at the
      column inlet whose pH deviates, more or less, from the bulk eluent's. If the
      local adsorption strength in this sample zone is greater than the bulk eluent's,
      the elution profiles are compressed. Under opposite conditions, the eluted bands
      are more or less deformed and may even be split; completely different
      deformations can even take place for different kinds of salt combinations.
      Explanations of these, and other, effects, together with detailed guidelines for
      proper sample preparation to avoid peak deformations, are given. 

PMID- 24133007
TI  - Common cerebral networks associated with distinct deep brain stimulation targets
      for cluster headache.
AB  - BACKGROUND: Several centers have reported efficacious cluster headache
      suppression with deep brain stimulation (DBS) of the hypothalamic region using a
      variety of targets. While the connectivity of some of these targets has
      individually been studied, commonalities across these targets, especially with
      respect to network-level connectivity, have not previously been explored.
      METHODS: We examined the anatomic connectivity of the four distinct DBS targets
      reported in the literature using probabilistic diffusion tensor tractography in
      normal subjects. RESULTS: Despite being described as hypothalamic, the DBS
      targets localized in the midbrain tegmentum posterior to the hypothalamus. Common
      tracts across DBS targets and subjects included projections to the ipsilateral
      hypothalamus, reticular formation, and cerebellum. DISCUSSION: Although DBS
      target coordinates are not located within the hypothalamus, a strong connection
      between DBS targets and the hypothalamus likely exists. Moreover, a common
      projection to the medial ipsilateral cerebellum was identified. Understanding the
      common connectivity of DBS-targeted regions may elucidate anatomic pathways that
      are involved in modulating cluster headache attacks and facilitate more precise
      patient-specific targeting of DBS.

PMID- 24133009
TI  - Increases in disturbance and reductions in habitat size interact to suppress
      predator body size.
AB  - Food webs are strongly size-structured so will be vulnerable to changes in
      environmental factors that affect large predators. However, mechanistic
      understanding of environmental controls of top predator size is poorly developed.
      We used streams to investigate how predator body size is altered by three
      fundamental climate change stressors: reductions in habitat size, increases in
      disturbance and warmer temperatures. Using new survey data from 74 streams, we
      showed that habitat size and disturbance were the most important stressors
      influencing predator body size. A synergistic interaction between that habitat
      size and disturbance due to flooding meant the sizes of predatory fishes peaked
      in large, benign habitats and their body size decreased as habitats became either
      smaller or harsher. These patterns were supported by experiments indicating that
      habitat-size reductions and increased flood disturbance decreased both the
      abundance and biomass of large predators. This research indicates that
      interacting climate change stressors can influence predator body size, resulting
      in smaller predators than would be predicted from examining an environmental
      factor in isolation. Thus, climate-induced changes to key interacting
      environmental factors are likely to have synergistic impacts on predator body
      size which, because of their influence on the strength of biological
      interactions, will have far-reaching effects on food-web responses to global
      environmental change. 

PMID- 24133010
TI  - Enantioselective functionalization of radical intermediates in redox catalysis:
      copper-catalyzed asymmetric oxytrifluoromethylation of alkenes.

PMID- 24133011
TI  - Dynamics of palladium on nanocarbon in the direct synthesis of H2O2.
AB  - This work aims to clarify the nanostructural transformation accompanying the loss
      of activity and selectivity for the hydrogen peroxide synthesis of palladium and
      gold-palladium nanoparticles supported on N-functionalized carbon nanotubes. High
      resolution X-ray photoemission spectroscopy (XPS) allows the discrimination of
      metallic palladium, electronically modified metallic palladium hosting
      impurities, and cationic palladium. This is paralleled by the morphological
      heterogeneity observed by high-resolution TEM, in which nanoparticles with an
      average size of 2 nm coexisted with very small palladium clusters. The
      morphological distribution of palladium is modified after reaction through
      sintering and dissolution/redeposition pathways. The loss of selectivity is
      correlated to the extent to which these processes occur as a result of the
      instability of the particle at the carbon surface. We assign beneficial activity
      in the selective hydrogenation of oxygen to palladium clusters with a modified
      electronic structure compared with palladium metal or palladium oxides. These
      beneficial species are formed and stabilized on carbons modified with nitrogen
      atoms in substitutional positions. The formation of larger metallic palladium
      particles not only reduces the number of active sites for the synthesis, but also
      enhances the activity for deep hydrogenation to water. The structural instability
      of the active species is thus detrimental in a dual way. Minimizing the chance of
      sintering of palladium clusters by all means is thus the key to better performing
      catalysts.

PMID- 24133012
TI  - Regulation of cuticle pigmentation in drosophila by the nutrient sensing insulin
      and TOR signaling pathways.
AB  - BACKGROUND: Insect pigmentation is a phenotypically plastic trait that plays a
      role in thermoregulation, desiccation tolerance, mimicry, and sexual selection.
      The extent and pattern of pigmentation of the abdomen and thorax in Drosophila
      melanogaster is affected by environmental factors such a growth temperature and
      access to the substrates necessary for melanin biosynthesis. This study aimed to
      determine the effect of nutritional status during development on adult
      pigmentation and test whether nutrient sensing through the Insulin/IGF and target
      of rapamycin (TOR) pathways regulates the melanization of adult cuticle in
      Drosophila. RESULTS: Flies reared on low quality food exhibit decreased
      pigmentation, which can be phenocopied by inhibiting expression of the Insulin
      receptor (InR) throughout the entire fly during mid to late pupation. The loss of
      Insulin signaling through PI3K/Akt and FOXO in the epidermis underlying the
      developing adult cuticle causes a similar decrease in adult pigmentation,
      suggesting that Insulin signaling acts in a cell autonomous manner to regulate
      cuticle melanization. In addition, TOR signaling increases pigmentation in a cell
      autonomous manner, most likely through increased S6K activity. CONCLUSION: These
      results suggest that nutrient sensing through the Insulin/IGF and TOR pathways
      couples cuticle pigmentation of both male and female Drosophila with their
      nutritional status during metamorphosis.

PMID- 24133013
TI  - Development and application of a LC-MS/MS assay for the simultaneous
      quantification of edaravone and taurine in beagle plasma.
AB  - An LC-MS/MS method was developed and validated for the simultaneous
      quantification of edaravone and taurine in beagle plasma. The plasma sample was
      deproteinized using acetonitrile containing formic acid. Chromatographic
      separations were achieved on an Agilent Zorbax SB-Aq (100 * 2.1 mm, 3.5 MUm)
      column, with a gradient of water (containing 0.03% formic acid) and methanol as
      the mobile phase at a flow rate of 0.3 mL/min. The analyte detection was carried
      out in multiple reaction monitoring mode and the optimized precursor-to-product
      transitions of m/z [M+H](+) 175.1 -> 133.0 (edaravone), m/z [M+H](+) 189.1 ->
      147.0 (3-methyl-1-p-tolyl-5-pyrazolone, internal standard, IS), m/z [M-H](-)
      124.1->80.0 (taurine), and m/z [M-H](-) 172.0 -> 80.0 (sulfanilic acid, IS) were
      employed to quantify edaravone, taurine, and their corresponding ISs,
      respectively. The LOD and the lower LOQ were 0.01 and 0.05 MUg/mL for edaravone
      and 0.66 and 2 MUg/mL for taurine, respectively. The calibration curves of these
      two analytes demonstrated good linearity (r > 0.99). All the validation data
      including the specificity, precision, recovery, and stability conformed to the
      acceptable requirements. This validated method has successfully been applied in
      the pharmacokinetic study of edaravone and taurine mixture in beagle dogs. 

PMID- 24133015
TI  - Synthetically important alkali-metal utility amides: lithium, sodium, and
      potassium hexamethyldisilazides, diisopropylamides, and tetramethylpiperidides.
AB  - Most synthetic chemists will have at some point utilized a sterically demanding
      secondary amide (R2 N(-) ). The three most important examples, lithium
      1,1,1,3,3,3-hexamethyldisilazide (LiHMDS), lithium diisopropylamide (LiDA), and
      lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-the "utility amides"-have long been
      indispensible particularly for lithiation (Li-H exchange) reactions. Like
      organolithium compounds, they exhibit aggregation phenomena and strong Lewis
      acidity, and thus appear in distinct forms depending on the solvents employed.
      The structural chemistry of these compounds as well as their sodium and potassium
      congeners are described in the absence or in the presence of the most
      synthetically significant donor solvents tetrahydrofuran (THF) and N,N,N',N'
      tetramethylethylenediamine (TMEDA) or closely related solvents. Examples of
      hetero-alkali-metal amides, an increasingly important composition because of the
      recent escalation of interest in mixed-metal synergic effects, are also included.

PMID- 24133017
TI  - Octanol/water partitioning simulation by RP-HPLC for structurally diverse acidic
      drugs: comparison of three columns in the presence and absence of n-octanol as
      the mobile phase additive.
AB  - The advantageous effect of n-octanol as a mobile phase additive for lipophilicity
      assessment of structurally diverse acidic drugs both in the neutral and ionized
      form was explored. Two RP C18 columns, ABZ+ and Aquasil, were used for the
      determination of logkw indices, and the results were compared with those
      previously reported on a base-deactivated silica column. At pH 2.5, the use of n
      octanol-saturated buffer as the mobile phase aqueous component led to high
      quality 1:1 correlation between logkw and logP for the ABZ+ column, while
      inferior statistics were obtained for Aquasil. At physiological pH, the
      correlations were significantly improved if strongly ionized acidic drugs were
      treated separately from weakly ionized ones. In the latter case, 1:1 correlations
      between logD7.4 and logkw(oct) indices were obtained in the presence of 0.25% n
      octanol. Concerning strongly ionized compounds, adequate correlations were
      established under the same conditions; however, slopes were significantly lower
      than unity, while large negative intercepts were obtained. According to the
      absolute difference (diff = logD7.4 - logkw) pattern, base-deactivated silica
      showed a better performance than ABZ+, however, the latter seems more efficient
      for the lipophilicity assessment of highly lipophilic acidic compounds. Aquasil
      may be the column of choice if logD7.4<3 with the limitation, however, that very
      hydrophilic compounds cannot be measured.

PMID- 24133018
TI  - Controlling size-induced phase transformations using chemically designed
      nanolaminates.

PMID- 24133019
TI  - Yeast three-hybrid screening for identifying anti-tuberculosis drug targets.
AB  - Mycobacterium goes yeast: Target deconvolution of anti-tuberculosis drugs can be
      a very challenging task. Here we report a yeast 3-hybrid system that allows
      promising small molecules to be screened for protein targets of a pathogen in
      nontoxic yeast cells. The system employs libraries of randomly fragmented
      bacterial DNA and offers a technically simple alternative approach for target
      identification. 

PMID- 24133020
TI  - Microstructure and interfacial chemistry of pure and La-doped BiFeO3 thin films.
AB  - We report on the microstructure and interfacial chemistry of thin films of pure
      and La-doped multiferroic bismuth ferrite (Bi1-x Lax FeO3 or BLFO), synthesized
      on Indium Tin Oxide-coated glass substrates by solution-deposition technique and
      studied using scanning transmission electron microscopy. Our results show that
      undoped and La-doped thin films are polycrystalline with distorted rhombohedral
      structure without any presence of any line or planar defect in the films. In
      addition, the films with La doping did not show any structural change and
      maintain the equilibrium structure. Cross section compositional analysis using X
      ray energy dispersive spectrometry did not reveal either any interdiffusion of
      chemical species or formation of reaction product at the film-substrate
      interface. However, a closer examination of the microstructure of the films shows
      tiny pores along with the presence of approximately 2-3 nm thin amorphous layers,
      which may have significant influence on the functional properties of such films.

PMID- 24133021
TI  - Facile deposition of multicolored electrochromic metal-organic framework thin
      films.

PMID- 24133022
TI  - Immobilized ECM molecules and the effects of concentration and surface type on
      the control of NSC differentiation.
AB  - New developments in growth factor and pharmaceutical control of cells for neural
      regenerative strategies have built a need for high throughput assays to
      conveniently screen these treatments in vitro before moving to more complex
      experiments. Towards this application, we have studied an easy and highly
      reproducible culture regime with a renewable cell source for central nervous
      system (CNS) strategies. Adult neural stem cells (NSCs) derived from the CNS are
      attractive for use in screening assay because they are easily expanded and can
      differentiate into all major CNS cell types. NSCs were cultured on glass alone or
      methacrylamide chitosan (MAC) hydrogel coated glass substrates, immobilized with
      extracellular matrix (ECM) proteins collagen and laminin at varying densities.
      Proteins were also adsorbed on the surfaces as a control. We found that adsorbed
      protein on hydrogel coated glass resulted in the highest cell densities after 8
      d, over twice the density of immobilized groups or adsorbed protein on glass. No
      significant differences were observed between collagen, laminin, or both proteins
      together regarding cell differentiation (p > 0.05); however, the morphological
      spreading and branching of differentiated NSC processes was enhanced on MAC
      substrates with covalently immobilized laminin protein. The results of this study
      suggest that a soft MAC hydrogel surface with adsorbed protein would be most
      desirable for specifying neuronal differentiation of large numbers of stem cells
      due to the high cellularities they supported.

PMID- 24133023
TI  - Electropolymerization of single-walled carbon nanotubes composited with
      polypyrrole as a solid-phase microextraction fiber for the detection of
      acrylamide in food samples using GC with electron-capture detection.
AB  - We developed a solid-phase microextraction coupled to GC with electron-capture
      detection method for the detection of acrylamide in food samples. Single-walled
      carbon nanotubes and polypyrrole were electropolymerized onto a stainless-steel
      wire as a coating, which possessed a homogeneous, porous, and wrinkled surface,
      chemical and mechanical stability, long lifespan (over 300 extractions), and good
      extraction efficiency for acrylamide. The linearity range between the signal
      intensity and the acrylamide concentration was found to be in the range 0.001-1
      MUg/mL, and the coefficient of determination was 0.9985. The LOD, defined as
      three times the baseline noise, was 0.26 ng/mL. The reproducibility for each
      single fiber (n = 6) and the fiber-to-fiber (n = 5) repeatability prepared in the
      same batch were less than 4.1 and 11.2%, respectively.

PMID- 24133024
TI  - A randomised controlled trial comparing a thermal massager with artificial
      teardrops for the treatment of dry eye.
AB  - BACKGROUND: To evaluate the efficacy and safety of a thermal massager for the
      treatment of dry eye syndrome. METHODS: Ninety-five patients with dry eye
      syndrome were randomly assigned to receive either the thermal massager or
      artificial tears treatment. Thermal massage consisted of vibration, massage and
      thermotherapy and was carried out twice daily. Patients in the artificial tears
      group received 0.1% sodium hyaluronate solution five times daily. The Ocular
      Surface Disease Index (OSDI) score, break-up time (BUT), Schirmer test,
      fluorescein staining of the cornea, tear osmolarity test and adverse events were
      evaluated after 4 weeks. RESULTS: OSDI showed a significant improvement in both
      groups and improvement was significantly greater in thermal massager group
      (p=0.032). BUT and fluorescein staining also indicated significant improvement.
      No differences were found between the two groups in measures other than the OSDI.
      Adverse events were mild and transient. CONCLUSIONS: Thermal massage was
      effective in improving dry eye syndrome both subjectively and objectively. It was
      safe and seems to be a useful treatment option.

PMID- 24133025
TI  - Brachytherapy and endoresection for choroidal melanoma: a cohort study.
AB  - AIM: To report and compare the outcomes of brachytherapy and endoresection in the
      conservative treatment of medium sized choroidal melanoma. METHODS: A
      retrospective cohort study. Medium tumours were defined as 2.5-10 mm in height
      and less than 16 mm in the widest diameter. Consecutive patients undergoing
      brachytherapy at Groote Schuur Hospital were compared with a cohort undergoing
      endoresection from a national database. RESULTS: 148 brachytherapy and 22
      endoresection patients were followed for a median of 55.4 and 62.4 months,
      respectively. Tumours undergoing endoresection were thicker (7.3 vs 4.9 mm,
      p<0.001, Wilcoxon rank-sum test) and further from the fovea (5.2 vs 3.7 mm,
      p=0.05, Wilcoxon rank-sum test) than those treated with brachytherapy. Visual
      acuity of 6/18 or better was maintained in 41% of the endoresection group and 35%
      of the brachytherapy group. The likelihood of achieving a final visual acuity of
      better than 2/60 was 22% higher in the endoresection group (risk ratio 1.22, 95%
      CI 1.02 to 1.28, p=0.034). Rates of local recurrence (18.2% vs 14.9%, p=0.75) and
      metastases or death (18.2% vs 14.2%, p=0.75) were higher in the endoresection
      group, and the enucleation rate was lower in this group (4.6% vs 10.8%, p=0.70)
      but these were not statistically significant. CONCLUSIONS: The outcomes observed
      in this small cohort of endoresection patients suggest that endoresection of
      selected tumours may achieve better visual outcomes than brachytherapy. Rates of
      local recurrence, enucleation and metastases following endoresection require
      further research. Local recurrence is likely to be influenced by consolidation
      treatment methods.

PMID- 24133026
TI  - Recipient corneal thickness and visual outcome after Descemet's stripping
      automated endothelial keratoplasty.
AB  - BACKGROUND: Descemet's stripping automated endothelial keratoplasty (DSAEK) is
      widely performed for endothelial failure. Unfortunately, the visual outcome is
      often mediocre and the underlying cause unclear. This study examines whether
      corneal light scatter and recipient corneal thickness (RCT) influence the visual
      outcome after DSAEK. METHODS: Patients attending clinical control after DSAEK
      were recruited during 4 months. In total, 125 eyes from 93 patients were
      enrolled. Postoperative time averaged 20+/-13 months. Data from previous controls
      were also reviewed. Examinations included corrected distance visual acuity
      (CDVA), Pentacam and anterior-segment OCT. From OCT and Pentacam data, RCT and
      lamellar graft thickness (LGT) were determined. Corneal densitometry was
      estimated from Pentacam images. RESULTS: 6 months after DSAEK, RCT measured 482+/
      27 MUm. After 3 years, RCT was significantly higher, measuring 505+/-23 MUm.
      Pentacam and OCT showed similar variations in RCT. Also, in paired observations,
      from patients with previous controls, RCT increased significantly. Concurrently,
      corneal densitometry decreased and CDVA improved from 0.30+/-0.13 logMAR by 6
      months to 0.17+/-0.08 logMAR by 4 years. No changes in LGT were observed. Changes
      in RCT, densitometry and CDVA were significantly correlated. CONCLUSIONS: The
      study suggests that changes in RCT and corneal densitometry are important for the
      visual outcome after DSAEK.

PMID- 24133027
TI  - Effects of unilateral internal jugular vein removal on intraocular pressure.
AB  - PURPOSE: To investigate the intraocular pressure (IOP) and retinal nerve fibre
      layer (RNFL) thickness after ipsilateral neck dissection with internal jugular
      vein (IJV) removal for head and neck tumours. METHODS: A computer search was
      performed to identify all patients who were treated with neck dissection with
      unilateral IJV removal from 2005 to 2012. All patients underwent a complete
      ophthalmological examination including measurement of IOP by Goldmann applanation
      tonometry and the average RNFL thickness using a Spectralis optical coherence
      tomography. The following analyses were made between the eyes on the side of the
      IJV removal versus the eye on the contralateral side: gonioscopy, IOP, vertical
      cup-disc ratio (VCDR) and peripapillary RNFL. Correlation analysis between the
      year of operation and IOP was done using the Pearson correlation coefficient.
      RESULTS: This prospective cross-sectional study recruited 38 patients. The median
      age at operation was 59.5 years (range 33-87 years). There were 26 males and 12
      females. Exactly half of the patients had left IJV removal and the remaining half
      had right IJV removal. The median interval from neck dissection to eye assessment
      was 46.5 months (range 11-97 months). There was no significant difference between
      the ipsilateral and contralateral side in terms of gonioscopy, IOP, VCDR, and
      RNFL. There was no significant correlation between the duration of IJV removal
      and IOP (p=0.8). CONCLUSIONS: Ipsilateral IJV removal after neck dissection did
      not result in any significant differences in the average peripapillary RNFL
      thickness or IOP compared to the contralateral eye at a mean of 46.5 months
      postoperatively.

PMID- 24133028
TI  - Macular burns resulting from the accidental use of selective laser
      trabeculoplasty mode during a laser capsulotomy.

PMID- 24133029
TI  - Involvement of HMGB1 mediated signalling pathway in diabetic retinopathy:
      evidence from type 2 diabetic rats and ARPE-19 cells under diabetic condition.
AB  - AIMS: Inflammation is considered to play a critical role in the pathogenesis of
      diabetic retinopathy, and high mobility group box protein 1 (HMGB1) could promote
      inflammation as an alarmin. We investigated the expression of HMGB1 signalling
      pathway components in type 2 diabetic rat retinas and in high glucose cultured
      ARPE-19 cells. METHODS: Retinal expression of HMGB1 and its receptors in type 2
      diabetic rats were detected by western blot and immunohistochemistry. ARPE-19
      cells were cultured with low glucose, high glucose (with or without anti-HMGB1
      antibody) or mannitol (control) for different lengths of time (12, 24, 48, 72 h).
      Then expression of HMGB1 and its receptors was measured by immunocytochemistry,
      ELISA or western blot. Nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB) activity and tumour necrosis factor alpha (TNFalpha)/vascular
      endothelial growth factor (VEGF) production in retinas as well as in ARPE-19
      cells were detected by ELISA. Furthermore, blood-retinal barrier permeability and
      ARPE-19 cell viability were measured by Evans-Blue and Cell Counting Kit-8 assay,
      respectively. RESULTS: HMGB1 signalling pathway components including receptors
      for HMGB1 as well as NF-kappaB and TNFalpha/VEGF were significantly upregulated
      in type 2 diabetic retinas and in high glucose treated ARPE-19 cells, compared to
      their respective counterparts. HMGB1 blockage significantly alleviated NF-kappaB
      activity and VEGF secretion in ARPE-19 cells cultured with high glucose. In
      addition, blood-retinal barrier permeability of the diabetic retinas increased,
      while cell viability of high glucose treated ARPE-19 cells decreased.
      CONCLUSIONS: Expression of HMGB1 signalling pathway components were increased in
      diabetic rat retinas and in ARPE-19 cells exposed to high glucose.

PMID- 24133030
TI  - Choroidal varix elevates macula following Valsalva manoeuvre.

PMID- 24133031
TI  - Identification of a pepducin acting as S1P3 receptor antagonist.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid with key functions in the
      immune, inflammatory, and cardiovascular systems. S1P exerts its action through
      the interaction with a family of five known G protein-coupled receptors, named
      S1P(1-5). Among them, S1P(3) has been implicated in the pathological processes of
      a number of diseases, including sepsis and cancer. KRX-725 (compound 1) is a
      pepducin that mimics the effects of S1P by triggering specifically S1P(3). Here,
      aiming to identify novel S1P(3) antagonists, we carried out an alanine scanning
      analysis to address the contribution of the side chains of each amino acid
      residue to the peptide function. Then, deleted peptides from both the C- and N
      terminus were prepared in order to determine the minimal sequence for activity
      and to identify the structural requirements for agonistic and, possibly,
      antagonistic behaviors. The pharmacological results of the Ala-scan derived
      compounds (2-10) suggested a high tolerance of the pepducin 1 to amino acid
      substitutions. Importantly, the deleted peptide 16 has the ability to inhibit, in
      a dose-dependent manner, both pepducin 1-induced vasorelaxation and fibroblast
      proliferation. Finally, a computational analysis was performed on the prepared
      compounds, showing that the supposed antagonists 16 and 17 appeared to be aligned
      with each other but not with the others. These results suggested a correlation
      between specific conformations and activities.

PMID- 24133032
TI  - Synthesis, characterization and optical studies of highly luminescent ZnS
      nanoparticles associated with hypromellose matrix as a green and novel
      stabilizer.
AB  - ZnS nanoparticles stabilized by a carbohydrate-based matrix, hypromellose
      (hydroxypropyl methylcellulose) were prepared via a wet chemical method. The
      nanocomposite was characterized by X-ray diffraction, transmission electon
      microscopy and Fourier transform infrared spectroscopy. X-Ray diffraction
      patterns revealed a zinc blende structure. Thermogravimetric analysis suggested
      that polymer attached to the surface decomposes at 700  degrees C. Absorption
      measurements were carried out and calculation of the diameter polydispersity
      index (DPI) suggests the formation of monodisperse nanoparticles. The optical
      properties of the as-prepared samples were studied by UV/vis spectroscopy and
      steady-state photoluminescence (PL) spectroscopy. The PL studies indicate the
      applicability of these nanoparticles as biocompatible sensors or luminescence
      markers in future.

PMID- 24133033
TI  - Charged metallopolymers as universal precursors for versatile cobalt materials.

PMID- 24133034
TI  - Dutch Dyslexia Programme.

PMID- 24133035
TI  - Precursors of developmental dyslexia: an overview of the longitudinal Dutch
      Dyslexia Programme study.
AB  - Converging evidence suggests that developmental dyslexia is a neurobiological
      disorder, characterized by deficits in the auditory, visual, and linguistic
      domains. In the longitudinal project of the Dutch Dyslexia Programme, 180
      children with a familial risk of dyslexia (FR) and a comparison group of 120
      children without FR (noFR) were followed from the age of 2 months up to 9 years.
      Children were assessed on (1) auditory, speech, and visual event-related
      potentials every half year between 2 and 41 months; (2) expressive and receptive
      language, motor development, behaviour problems, and home-literacy environment by
      questionnaires at the age of 2 and 3; (3) speech-language and cognitive
      development from 47 months onwards; and (4) preliteracy and subskills of reading,
      and reading development during kindergarten and Grades 2 and 3. With regard to
      precursors of reading disability, first analyses showed specific differences
      between FR and noFR children in neurophysiological, cognitive, and early language
      measures. Once reading tests administered from age 7 to 9 years were available,
      the children were divided into three groups: FR children with and without
      dyslexia, and controls. Analyses of the differences between reading groups
      yielded distinct profiles and developmental trajectories. On early speech and
      visual processing, and several cognitive measures, performance of the non
      dyslexic FR group differed from the dyslexic FR group and controls, indicating
      continuity of the influence of familial risk. Parental reading and rapid naming
      skills appeared to indicate their offspring's degree of familial risk.
      Furthermore, on rapid naming and nonverbal IQ, the non-dyslexic FR group
      performed similarly to the controls, suggesting protective factors. There are
      indications of differences between the FR and control groups, irrespective of
      reading outcome. These results contribute to the distinction between the deficits
      correlated to dyslexia as a manifest reading disorder and deficits correlated to
      familial risk only.

PMID- 24133036
TI  - Molecular genetics of dyslexia: an overview.
AB  - Dyslexia is a highly heritable learning disorder with a complex underlying
      genetic architecture. Over the past decade, researchers have pinpointed a number
      of candidate genes that may contribute to dyslexia susceptibility. Here, we
      provide an overview of the state of the art, describing how studies have moved
      from mapping potential risk loci, through identification of associated gene
      variants, to characterization of gene function in cellular and animal model
      systems. Work thus far has highlighted some intriguing mechanistic pathways, such
      as neuronal migration, axon guidance, and ciliary biology, but it is clear that
      we still have much to learn about the molecular networks that are involved. We
      end the review by highlighting the past, present, and future contributions of the
      Dutch Dyslexia Programme to studies of genetic factors. In particular, we
      emphasize the importance of relating genetic information to intermediate
      neurobiological measures, as well as the value of incorporating longitudinal and
      developmental data into molecular designs.

PMID- 24133037
TI  - Dyslexia and early intervention: what did we learn from the Dutch Dyslexia
      Programme?
AB  - Part of the Dutch Dyslexia Programme has been dedicated to early intervention.
      The question of whether the genetically affected learning mechanism of children
      who are at familial risk (FR) of developing dyslexia could be influenced by
      training phoneme awareness and letter-sound associations in the prereading phase
      was investigated. The rationale was that intervention studies reveal insights
      about the weaknesses of the learning mechanisms of FR children. In addition, the
      studies aimed to gather practical insights to be used in the development of a
      system of early diagnosis and prevention. Focused on the last period of
      kindergarten before formal reading instruction starts in Grade 1, intervention
      methods with comparable samples and designs but differences in delivery mode (use
      of computer or manual), tutor (semi-professional or parent), location (at school
      or at home), and additional practices (serial rapid naming or simple word
      reading) have been executed to test the hypothesis that the incidence and degree
      of dyslexia can be reduced. The present position paper summarizes the Dutch
      Dyslexia Programme findings and relates them to findings of other studies. It is
      discussed that the Dutch studies provide evidence on why prevention of dyslexia
      is hard to accomplish. It is argued that effective intervention should not only
      start early but also be adapted to the individual and often long-lasting
      educational needs of children at risk of reading failure.

PMID- 24133038
TI  - The effectiveness of a 2-year supplementary tutor-assisted computerized
      intervention on the reading development of beginning readers at risk for reading
      difficulties: a randomized controlled trial.
AB  - Children with low (pre-)literacy skills may benefit from individual tutoring
      during the early phases of learning to read. Dutch at-risk students from 13
      schools received in first and second grade a computerized reading intervention,
      delivered by non-professional tutors at school. Digital logs indicated that
      treatment integrity was lower than intended; therefore, the intervention group
      was subdivided using a completion criterion. Third grade assessments revealed
      that the subgroup that had finished the program successfully (IF, N = 40) was
      able to read as fluent as the average reader, outperforming the subgroup that had
      not completely finished the program (InF, N = 31) as well as the group that had
      not worked with the program (controls, N = 66) on all reading measures. This
      study demonstrates that a well-implemented tutoring model can serve as a (cost
      )effective complement to the classroom practice for beginning readers.

PMID- 24133039
TI  - A new fluorescent derivatization reagent and its application to free fatty acid
      analysis in pomegranate samples using HPLC with fluorescence detection.
AB  - A new fluorescent labeling reagent has been developed for the determination of
      fatty acids (FAs) by HPLC with fluorescence detection. The derivatization
      conditions including the amount of derivatization reagent, temperature, and type
      of catalyst were investigated, the results indicated that the reaction proceeded
      within 30 min at 90 degrees C in the presence of K2CO3 catalyst. The maximal
      yield was obtained with a four- to fivefold molar reagent excess. The derivatives
      exhibited strong fluorescence with an excitation maximum at lambdaex = 245 nm and
      an emission maximum at lambdaem = 410 nm. Twenty-five FA derivatives were well
      separated by RP-HPLC on a Hypersil BDS C8 column in combination with gradient
      elution. All FAs were found to give excellent linear responses with correlation
      coefficients >0.9992. The method gave a low LOQ of 0.85-5.5 ng/mL (S/N of 10).
      The developed method was employed to analyze free FAs (FFAs) composition in
      pomegranate samples without any purification. FFAs in samples were doubly
      identified by HPLC retention time and protonated molecular ion corresponding to
      m/z [M+H]+. This newly developed method allows a highly sensitive determination
      of trace FFAs from pomegranate and other foodstuffs.

PMID- 24133040
TI  - Chitosan scaffold co-cultured with keratinocyte and fibroblast heals full 
      thickness skin wounds in rabbit.
AB  - This study evaluated the modulatory effect of chitosan sponge co-cultured with
      keratinocyte and fibroblast on wound healing. Dermal fibroblasts and keratinocyte
      isolated from rabbit skin were co-cultured on chitosan sponge, to fabricate cell
      loaded chitosan tissue engineered construct. Full thickness excision wounds
      created on the rabbit dorsum were treated with three types of graft materials - a
      noncellular chitosan graft, homologous keratinocyte fibroblast loaded chitosan,
      and a commercial product. Postgraft skin-wound samples were examined
      histomorphologically at 7th, 14th, and 28th day after staining with hematoxylin
      and eosin, picrosirius red and/or immunohistochemistry. Wound healing parameters
      considered were the extent of re-epithelialization, collagen deposition, and
      neoangiogenesis. The number of proliferating cells, vimentin positive cells, and
      alpha smooth muscle actin cells were also quantified. The histology results
      suggested that the grafts aided wound healing but, the cell-loaded graft induced
      a differential pattern of healing and had lower scarring tendency. The cell
      loaded tissue construct may be useful as a therapeutic graft for treating wounds
      where there is a total loss of tissue and cells as in burn injury.

PMID- 24133041
TI  - High-mobility, aligned crystalline domains of TIPS-pentacene with metastable
      polymorphs through lateral confinement of crystal growth.
AB  - Patterns composed of solvent wetting and dewetting regions promote lateral
      confinement of solution-sheared and lattice-strained TIPS-pentacene crystals.
      This lateral confinement causes aligned crystal growth, and the smallest patterns
      of 0.5 MUm wide solvent wetting regions promotes formation of highly strained,
      aligned, and single-crystalline TIPS-pentacene regions with mobility as high as
      2.7 cm(2) V(-1) s(-1) . 

PMID- 24133042
TI  - A simple and versatile method for the formation of arrays of giant vesicles with
      controlled size and composition.
AB  - A simple and versatile method for the Formation of Arrays of Giant Vesicles with
      Controlled Size and Composition. The ability of this technique to generate arrays
      of giant liposomes from a wide range of membrane lipids and protein compositions
      is demonstrated. The resulting vesicles are utilized for studying protein
      activity, lipid-protein interactions, and protein-protein interactions. 

PMID- 24133043
TI  - Synthesis, characterization, and biocompatibility of alternating block 
      polyurethanes based on PLA and PEG.
AB  - A series of alternating block polyurethanes (abbreviated as PULA-alt-PEG) and
      random block polyurethanes (abbreviated as PULA-ran-PEG) based on poly(L-lactic
      acid) (PLA) and poly(ethylene glycol) (PEG) were synthesized. The differences of
      PULA-alt/ran-PEG chemical structure, molecular weight, distribution, thermal
      properties, mechanical properties and static contact angle were systematically
      investigated. The PULA-alt/ran-PEG polyurethanes exhibited low T(g) (-47.3 ~ 
      34.4 degrees C), wide mechanical properties (stress sigma(t): 4.6-32.6 MPa,
      modulus E: 11.4-323.9 MPa and strain epsilon: 468-1530%) and low water contact
      angle (35.4-51.4 degrees ). Scanning electron microscope (SEM) observation showed
      that PULA-alt-PEG film displays rougher and more patterned surface morphology
      than PULA-ran-PEG does, due to more regular structures of PULA-alt-PEG.
      Hydrolytic degradation shows that degradation rate of random block polyurethane
      series PULA-ran-PEG is higher than the alternating counterpart PULA-alt-PEG. PLA
      segment degradation is faster than urethane linkage and PEG segment almost does
      not degrade in the buffer solution. Platelet adhesion study showed that all the
      polyurethanes possess excellent hemocompatibility. The cell culture assay
      revealed that PULA-alt/ran-PEG polyurethanes were cell inert and unfavorable for
      the attachment of rat glial cell due to the hydrophilic characters of the
      materials.

PMID- 24133044
TI  - Contact-mediated quenching for RNA imaging in bacteria with a fluorophore-binding
      aptamer.

PMID- 24133045
TI  - Comparative proteomics of dehydration response in the rice nucleus: new insights
      into the molecular basis of genotype-specific adaptation.
AB  - Dehydration is the most crucial environmental factor that considerably reduces
      the crop harvest index, and thus has become a concern for global agriculture. To
      better understand the role of nuclear proteins in water-deficit condition, a
      nuclear proteome was developed from a dehydration-sensitive rice cultivar IR-64
      followed by its comparison with that of a dehydration-tolerant c.v. Rasi. The 2DE
      protein profiling of c.v. IR-64 coupled with MS/MS analysis led to the
      identification of 93 dehydration-responsive proteins (DRPs). Among those
      identified proteins, 78 were predicted to be destined to the nucleus, accounting
      for more than 80% of the dataset. While the detected number of protein spots in
      c.v. IR-64 was higher when compared with that of Rasi, the number of DRPs was
      found to be less. Fifty-seven percent of the DRPs were found to be common to both
      sensitive and tolerant cultivars, indicating significant differences between the
      two nuclear proteomes. Further, we constructed a functional association network
      of the DRPs of c.v. IR-64, which suggests that a significant number of the
      proteins are capable of interacting with each other. The combination of nuclear
      proteome and interactome analyses would elucidate stress-responsive signaling and
      the molecular basis of dehydration tolerance in plants. 

PMID- 24133047
TI  - Nkx2-5 lineage tracing visualizes the distribution of second heart field-derived
      aortic smooth muscle.

PMID- 24133046
TI  - Characterization of scaffold carriers for BMP9-transduced osteoblastic progenitor
      cells in bone regeneration.
AB  - Successful bone tissue engineering at least requires sufficient osteoblast
      progenitors, efficient osteoinductive factors, and biocompatible scaffolding
      materials. We have demonstrated that BMP9 is one of the most potent factors in
      inducing osteogenic differentiation of mesenchymal progenitors. To facilitate the
      potential use of cell-based BMP9 gene therapy for bone regeneration, we
      characterize the in vivo osteoconductive activities and bone regeneration
      potential of three clinically used scaffold materials, type I collagen sponge,
      hydroxyapatite-tricalcium phosphate (HA-TCP), and demineralized bone matrix
      (DBM), using BMP9-expressing C2C12 osteoblastic progenitor cells. We find that
      recombinant adenovirus-mediated BMP9 expression effectively induces osteogenic
      differentiation in C2C12 cells. Although direct subcutaneous injection of BMP9
      transduced C2C12 cells forms ectopic bony masses, subcutaneous implantation of
      BMP9-expressing C2C12 cells with collagen sponge or HA-TCP scaffold yields the
      most robust and mature cancellous bone formation, whereas the DBM carrier group
      forms no or minimal bone masses. Our results suggest that collagen sponge and HA
      TCP scaffold carriers may provide more cell-friendly environment to support the
      survival, propagation, and ultimately differentiation of BMP9-expressing
      progenitor cells. This line of investigation should provide important
      experimental evidence for further preclinical studies in BMP9-mediated cell-based
      approach to bone tissue engineering.

PMID- 24133048
TI  - Voltage-controlled nonvolatile molecular memory of an azobenzene monolayer
      through solution-processed reduced graphene oxide contacts.
AB  - The solution-processed fabrication of an azobenzene (ABC10) monolayer-based
      nonvolatile memory device on a reduced graphene oxide (rGO) electrode is
      successfully accomplished. Trans--cis isomerizations of ABC10 between two rGO
      electrodes in a crossbar device are controlled by applied voltage. An rGO soft
      contact top electrode plays an important role in the conformational-change
      dependent conductance switching process of an ABC10 monolayer. 

PMID- 24133050
TI  - In macropore tryptic digestion at acidic pH and its implication for proteomics.
AB  - Gan et al. (Proteomics 2013, 13, 3117-3123) described a new "macropore" protocol
      for effective protein digestion by trypsin suitable for a wide range of pH
      including acidic pH. It was effective not only in experiments with solutions of a
      model protein (myoglobin), but also with a subfraction of rat liver cytosol. This
      significantly simplifies and accelerates protein digestion procedures for
      subsequent MS. However, further studies are needed to find limits of experimental
      applicability of the described protocol in proteomics. 

PMID- 24133051
TI  - Photoredox transformations with dimeric gold complexes.

PMID- 24133052
TI  - Photo quiz: nausea and emesis in a complicated patient.

PMID- 24133053
TI  - Risks of "blind" automated identification systems in medical microbiology.

PMID- 24133054
TI  - Reply to "risks of 'blind' automated identification systems in medical
      microbiology".

PMID- 24133057
TI  - A voxel-based morphometry study of anosmic patients.
AB  - OBJECTIVE: The aim of our study was to compare volume change in grey matter (GM)
      and white matter (WM) in a group of subjects with anosmia and a healthy control
      group. We tried to find a regular pattern of atrophy within and between GM and WM
      and to determine whether any particular areas are more sensitive to olfactory
      injury. METHODS: There were 19 anosmic patients and 20 age- and sex-matched
      control subjects. We acquired MR images on a 3-T scanner and performed voxel
      based morphometry using the VBM8 toolbox and SPM8 in a MATLAB(r) (MathWorks(r),
      Natick, MA) environment. RESULTS: Patients with anosmia showed a significant
      decrease in GM volume, mainly in the anterior cingulate cortex, middle temporal
      gyrus, superior temporal gyrus, fusiform gyrus, supramarginal gyrus, superior
      frontal gyrus, middle frontal gyrus, middle occipital gyrus, anterior insular
      cortex and cerebellum. In addition, we observed volume decreases in smaller areas
      such as the piriform cortex, the inferior temporal gyrus, the precuneus and the
      subcallosal gyrus. All WM areas with atrophy were near those GM areas that
      experienced volume loss. There was more volume atrophy in GM areas corresponding
      to WM areas with more volume loss. Atrophy increased with disease duration.
      CONCLUSION: There is simultaneous atrophy in GM and WM, and the degree of atrophy
      is greater with longer disease duration. Different GM and WM areas have different
      sensitivities to olfactory injury. ADVANCES IN KNOWLEDGE: This study examines the
      atrophy pattern in and between GM and WM-a subject that has not been widely
      researched previously.

PMID- 24133058
TI  - A national dosimetry audit of intraoperative radiotherapy.
AB  - OBJECTIVE: National dosimetry audits are a fundamental part of quality assurance
      in radiotherapy, especially for new techniques. Intraoperative radiotherapy with
      a compact mobile kilovoltage X-ray source is a novel approach for the treatment
      of breast and other cancers. All seven current clinical sites in the UK were
      audited by a single visiting group and set of measurement equipment. METHODS:
      Measurements of output, isotropy and depth doses were performed using an ion
      chamber in solid water, thermoluminescent dosemeters and radiochromic film,
      respectively. RESULTS: The mean difference between measured and planned dose
      across all centres was -3.2+/-2.7%. Measured isotropy was within +/-3% around the
      lateral plane of the X-ray source and +11+/-4% in the forward direction compared
      with the lateral plane. Measured depth doses were agreed within 5+/-2% of
      manufacturer-provided calibration values or a mean gamma index of 97% at a
      tolerance of 7%/0.5 mm. CONCLUSION: Agreement within measurement uncertainties
      was found for all three parameters except forward anisotropy, which is unlikely
      to be clinically significant. Steep dose gradients increase the sensitivity to
      small variations in positioning, but these tests are practical for use in
      interdepartmental audits and local baseline comparison. ADVANCES IN KNOWLEDGE:
      The first UK interdepartmental audit of intraoperative radiotherapy builds
      confidence in the delivery of this treatment.

PMID- 24133059
TI  - Hypolipemic effect of Garcinia cambogia in obese women.
AB  - Garcinia cambogia seems to promote weight reduction and improvement on lipid
      profile by its major compound, hydroxycitric acid (HCA), blocking ATP
      citratelyase, potentially inhibiting lipogenesis. Furthermore, it is suggested
      that its extract is able to change the adipokine levels. Thus, the aim of this
      study was to analyse the effect of G. cambogia on the lipid profile, endocrine,
      calorimetric and anthropometric parameters of obese women. The women (BMI > 25
      kg/m(2) ; age 25-60 years), divided in treated (n = 30) and control (n = 13)
      groups, received 2.4 g (800 mg 3*/day) of garcinia extract (50% of HCA) or
      placebo during 60 days, respectively, as well as dietary control. Weight, BMI,
      waist-hip ratio and percentage of fat mass, resting metabolic rate, respiratory
      coefficient, triglycerides (TG), total cholesterol, HDL and LDL, leptin and
      insulin serum levels were evaluated. TG was significantly reduced in the treated
      group (p = 0.0002) and the post-treatment variation was different compared to the
      placebo group (p = 0.04). No significant response was observed on other variables
      of the lipid profile, or on the anthropometric and calorimetric parameters.
      Leptin and insulin levels did not change significantly after the treatment. The
      short-term treatment with G. cambogia demonstrated a hypotriglyceridemic effect,
      which does not appear to be related to changes in leptinemia.

PMID- 24133060
TI  - Enterotoxigenic Escherichia coli infection and intestinal thiamin uptake: studies
      with intestinal epithelial Caco-2 monolayers.
AB  - Infections with enteric pathogens like enterotoxigenic Escherichia coli (ETEC) is
      a major health issue worldwide and while diarrhea is the major problem,
      prolonged, severe, and dual infections with multiple pathogens may also
      compromise the nutritional status of the infected individuals. There is almost
      nothing currently known about the effect of ETEC infection on intestinal
      absorptions of water-soluble vitamins including thiamin. We examined the effect
      of ETEC infection on intestinal uptake of the thiamin using as a model the human
      derived intestinal epithelial Caco-2 cells. The results showed that infecting
      confluent Caco-2 monolayers with live ETEC (but not with boiled/killed ETEC or
      nonpathogenic E. coli) or treatment with bacterial culture supernatant led to a
      significant inhibition in thiamin uptake. This inhibition appears to be caused by
      a heat-labile and -secreted ETEC component and is mediated via activation of the
      epithelial adenylate cyclase system. The inhibition in thiamin uptake by ETEC was
      associated with a significant reduction in expression of human thiamin
      transporter-1 and -2 (hTHTR1 and hTHTR2) at the protein and mRNA levels as well
      as in the activity of the SLC19A2 and SLC19A3 promoters. Dual infection of Caco-2
      cells with ETEC and EPEC (enteropathogenic E. coli) led to compounded inhibition
      in intestinal thiamin uptake. These results show for the first time that
      infection of human intestinal epithelial cells with ETEC causes a significant
      inhibition in intestinal thiamin uptake. This inhibition is mediated by a
      secreted heat-labile toxin and is associated with a decrease in the expression of
      intestinal thiamin transporters. 

PMID- 24133061
TI  - Holocarboxylase synthetase catalyzes biotinylation of heat shock protein 72,
      thereby inducing RANTES expression in HEK-293 cells.
AB  - In a recent mass spectrometry screen, we identified 108 new proteins that were
      modified endogenously by covalent binding of biotin; members of the heat shock
      superfamily of proteins, including heat shock protein 72 (HSP72), were
      overrepresented among the biotinylated proteins. Mammals respond to infections by
      secreting extracellular HSP72 (eHSP72), which elicits an immune response. Here,
      using mass spectrometry and site-directed mutagenesis, we identified five
      biotinylation sites in HSP72. We used coimmunoprecipitation, mass spectrometry,
      and limited proteolysis assays to demonstrate that HSP72 interacts physically
      with the protein biotin ligase holocarboxylase synthetase (HLCS), leading to
      biotinylation of residues K112, K128 K348, K361, K415, and, probably, additional
      lysines. Finally, we demonstrated that HLCS-dependent biotinylation of eHSP72
      increases expression of the chemokine regulated on activation normal T-expressed
      and presumably secreted (RANTES) by human embryonic kidney (HEK-293) cells. In
      conclusion, we report a novel endogenous modification of HSP72 and demonstrated
      that binding of biotin to eHSP72 prepares cells for a strong immune response. 

PMID- 24133062
TI  - Who's really in control: microbial regulation of protein trafficking in the
      epithelium.
AB  - Due to evolutionary pressure, there are many complex interactions at the
      interface between pathogens and eukaryotic host cells wherein host cells attempt
      to clear invading microorganisms and pathogens counter these mechanisms to
      colonize and invade host tissues. One striking observation from studies focused
      on this interface is that pathogens have multiple mechanisms to modulate and
      disrupt normal cellular physiology to establish replication niches and avoid
      clearance. The precision by which pathogens exert their effects on host cells
      makes them excellent tools to answer questions about cell physiology of
      eukaryotic cells. Furthermore, an understanding of these mechanisms at the host
      pathogen interface will benefit our understanding of how pathogens cause disease.
      In this review, we describe a few examples of how pathogens disrupt normal
      cellular physiology and protein trafficking at epithelial cell barriers to
      underscore how pathogens modulate cellular processes to cause disease and how
      this knowledge has been utilized to learn about cellular physiology. 

PMID- 24133063
TI  - Physical biology in cancer. 2. The physical biology of circulating tumor cells.
AB  - The identification, isolation, and characterization of circulating tumor cells
      (CTCs) promises to enhance our understanding of the evolution of cancer in
      humans. CTCs provide a window into the hematogenous, or "fluid phase," of cancer,
      underlying the metastatic transition in which a locally contained tumor spreads
      to other locations in the body through the bloodstream. With the development of
      sensitive and specific CTC identification and isolation methodologies, the role
      of CTCs in clinical diagnostics, disease surveillance, and the physical basis of
      metastasis continues to be established. This review focuses on the quantification
      of the basic biophysical properties of CTCs and the use of these metrics to
      understand the hematogenous dissemination of these enigmatic cells. 

PMID- 24133065
TI  - Carboxy terminus and pore-forming domain properties specific to Cx37 are
      necessary for Cx37-mediated suppression of insulinoma cell proliferation.
AB  - Connexin 37 (Cx37) suppresses cell proliferation when expressed in rat insulinoma
      (Rin) cells, an effect also manifest in vivo during vascular development and in
      response to tissue injury. Mutant forms of Cx37 with nonfunctional channels but
      normally localized, wild-type carboxy termini are not growth suppressive. Here we
      determined whether the carboxy-terminal (CT) domain is required for Cx37-mediated
      growth suppression and whether the Cx37 pore-forming domain can be replaced with
      the Cx43 pore-forming domain and still retain growth-suppressive properties. We
      show that despite forming functional gap junction channels and hemichannels, Cx37
      with residues subsequent to 273 replaced with a V5-epitope tag (Cx37-273tr*V5)
      had no effect on the proliferation of Rin cells, did not facilitate G1-cell cycle
      arrest with serum deprivation, and did not prolong cell cycle time comparably to
      the wild-type protein. The chimera Cx43*CT37, comprising the pore-forming domain
      of Cx43 and CT of Cx37, also did not suppress proliferation, despite forming
      functional gap junctions with a permselective profile similar to wild-type Cx37.
      Differences in channel behavior of both Cx37-273tr*V5 and Cx43*CT37 relative to
      their wild-type counterparts and failure of the Cx37-CT to interact as the Cx43
      CT does with the Cx43 cytoplasmic loop suggest that the Cx37-CT and pore-forming
      domains are both essential to growth suppression by Cx37. 

PMID- 24133064
TI  - Physical biology in cancer. 4. Physical cues guide tumor cell adhesion and
      migration.
AB  - As tumor cells metastasize from the primary tumor location to a distant secondary
      site, they encounter an array of biologically and physically heterogeneous
      microenvironments. While it is well established that biochemical signals guide
      all stages of the metastatic cascade, mounting evidence indicates that physical
      cues also direct tumor cell behavior, including adhesion and migration
      phenotypes. Physical cues acting on tumor cells in vivo include extracellular
      matrix mechanical properties, dimensionality, and topography, as well as
      interstitial flow, hydrodynamic shear stresses, and local forces due to
      neighboring cells. State-of-the-art technologies have recently enabled us and
      other researchers to engineer cell microenvironments that mimic specific physical
      properties of the cellular milieu. Through integration of these engineering
      strategies, along with physics, molecular biology, and imaging techniques, we
      have acquired new insights into tumor cell adhesion and migration mechanisms. In
      this review, we focus on the extravasation and invasion stages of the metastatic
      cascade. We first discuss the physical role of the endothelium during tumor cell
      extravasation and invasion and how contractility of endothelial and tumor cells
      contributes to the ability of tumor cells to exit the vasculature. Next, we
      examine how matrix dimensionality and stiffness coregulate tumor cell adhesion
      and migration beyond the vasculature. Finally, we summarize how tumor cells
      translate and respond to physical cues through mechanotransduction. Because of
      the critical role of tumor cell mechanotransduction at various stages of the
      metastatic cascade, targeting signaling pathways involved in tumor cell
      mechanosensing of physical stimuli may prove to be an effective therapeutic
      strategy for cancer patients. 

PMID- 24133066
TI  - A junction of transparency. Focus on "Functional effects of Cx50 mutations
      associated with congenital cataracts".

PMID- 24133068
TI  - Back to the future--the value of single protein species investigations.
AB  - In proteomics, in the past years, there was a focus on high throughput and
      reaching of large numbers of identified proteins with the basic discourse of
      protein expression. To avoid the impression of producing pure lists attempts are
      usually made to correlate proteins changed in amount between two biological
      situations to different pathways or protein interactions. This discourse is based
      on two simplifications, which limit the applicability of proteomics drastically:
      (i) it is sufficient to quantify a protein from several enzymatic digestion
      products; (ii) a biological situation is sufficiently described, if a peptide
      with its PTM is identified, resulting in long lists of modified peptides with
      data amounts, which are not anymore made accessible for the reader of a
      publication. The elucidation of N-terminal methylation of proteasome subunit Rpt1
      in yeast by Kimura et al. (Proteomics 2013, 13, 3167-3174), which represents the
      focus on one protein, shows the value of solid chemical analysis with a complete
      data documentation and paves the way to proteomics based on the protein
      speciation discourse. 

PMID- 24133067
TI  - Physical biology in cancer. 3. The role of cell glycocalyx in vascular transport
      of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) in blood are known to adhere to the luminal
      surface of the microvasculature via receptor-mediated adhesion, which contributes
      to the spread of cancer metastasis to anatomically distant organs. Such
      interactions between ligands on CTCs and endothelial cell-bound surface receptors
      are sensitive to receptor-ligand distances at the nanoscale. The sugar-rich
      coating expressed on the surface of CTCs and endothelial cells, known as the
      glycocalyx, serves as a physical structure that can control the spacing and,
      thus, the availability of such receptor-ligand interactions. The cancer cell
      glycocalyx can also regulate the ability of therapeutic ligands to bind to CTCs
      in the bloodstream. Here, we review the role of cell glycocalyx on the adhesion
      and therapeutic treatment of CTCs in the bloodstream. 

PMID- 24133070
TI  - Resveratrol and food effects on lifespan and reproduction in the model crustacean
      Daphnia.
AB  - Longevity is a highly variable life history trait and its variation is
      attributable to both genetic and environmental factors. Exploring well-known
      environmental factors in a new model system is a useful approach to explore
      taxonomic variation in plasticity of longevity. We examined responsiveness of the
      Daphnia pulex clone TCO to potentially related interventions that have been
      reported to extend lifespan: resveratrol and dietary restriction. First, we
      examined effects of resveratrol on lifespan and fecundity in TCO which were grown
      at moderate (12K cells Ankistrodesmus falcatus mL-1) and high (20K cells A.
      falcatus mL-1) food levels. We found no evidence for lifespan extension by
      resveratrol, but found a reduction of lifetime fecundity. The effect of
      resveratrol on fecundity was more pronounced early in life. We then conducted an
      additional life table to test the effect of dietary restriction on TCO.
      Surprisingly, reduced food level did not extend the lifespan of TCO, which
      contrasts with previous studies in D. pulex. Our results suggest that variation
      in the response to dietary restriction might be more common than previously
      thought. If resveratrol activates genes involved in the response to dietary
      restriction, genetic polymorphisms in dietary restriction will influence
      responses to resveratrol. Thus, this experiment suggests that careful re
      examination of resveratrol effects using diverse genotypes is required.

PMID- 24133075
TI  - Classification, measurement, and debate--the science of peritoneal dialysis.

PMID- 24133074
TI  - Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta
      analysis.
AB  - BACKGROUND: The association of long-term effects of inorganic arsenic (iAs)
      exposure with type 2 diabetes mellitus (T2DM) risk remains controversial.
      METHODS: A literature search was performed in PubMed, China National Knowledge
      Infrastructure and Web of Knowledge for relevant available articles published in
      English or Chinese from 1 January 1990 to 5 June 2013. Case-control, cohort or
      cross-sectional studies evaluating iAs and T2DM were included. The DerSimonian
      and Laird random effect model was adopted as the pooling method. Dose-response
      relationship was assessed by restricted cubic spline model and multivariate
      random-effect meta-regression. RESULTS: Of the 569 articles identified through
      searching databases, 17 published articles with 2,243,745 participants for iAs in
      drinking water and 21 083 participants for total arsenic (tAs) in urine were
      included for this meta-analysis. The pooled relative risk with 95% CI of T2DM for
      the highest versus lowest category of iAs exposure level in drinking water was
      1.75 (1.20 to 2.54). After removing three studies that had a strong effect on
      heterogeneity, the pooled relative risk was 1.23 (1.12 to 1.36). Dose-response
      analysis suggested T2DM risk increased by 13% (1.13 (1.00 to 1.27)) for every 100
      ug/L increment of iAs in drinking water. Significant association of T2DM risk
      with tAs in urine was also found 1.28 (1.14 to 1.44). CONCLUSIONS: This meta
      analysis indicates that long-term iAs exposure might be positively associated
      with T2DM risk.

PMID- 24133076
TI  - Vasopressin and osmoregulation: older than you thought.

PMID- 24133080
TI  - Is female sex really a risk factor for infectious death in peritoneal dialysis?

PMID- 24133081
TI  - Classification of encapsulating peritoneal sclerosis is important, but must
      encapsulate the entire spectrum of the disease.

PMID- 24133082
TI  - Towards standardized reporting in studies of encapsulating peritoneal sclerosis.

PMID- 24133083
TI  - Unroofing surgery with en bloc resection of the skin and tissues around the
      peripheral cuff.

PMID- 24133084
TI  - Comamonas testosteroni peritonitis secondary to dislocated intrauterine device
      and laparoscopic intervention in a continuous ambulatory peritoneal dialysis
      patient.

PMID- 24133085
TI  - Effect of intra-abdominal dialysate on bioimpedance-derived fluid volume status
      and body composition measurements in peritoneal dialysis patients.

PMID- 24133086
TI  - A rare and under-recognized pathogen in peritoneal dialysis peritonitis:
      Corynebacterium jeikeium.

PMID- 24133087
TI  - Tidying up the peritoneal dialysis modality classification: a proposal.

PMID- 24133088
TI  - Peritoneal dialysis combined with extracorporeal ultrafiltration in refractory
      heart failure: a case report.

PMID- 24133089
TI  - Increase in peritonitis rates with the reuse of drain tubing of the Fresenius
      Liberty cycler.

PMID- 24133097
TI  - A new variance stabilizing transformation for gene expression data analysis.
AB  - In this paper, we introduce a new family of power transformations, which has the
      generalized logarithm as one of its members, in the same manner as the usual
      logarithm belongs to the family of Box-Cox power transformations. Although the
      new family has been developed for analyzing gene expression data, it allows a
      wider scope of mean-variance related data to be reached. We study the analytical
      properties of the new family of transformations, as well as the mean-variance
      relationships that are stabilized by using its members. We propose a methodology
      based on this new family, which includes a simple strategy for selecting the
      family member adequate for a data set. We evaluate the finite sample behavior of
      different classical and robust estimators based on this strategy by Monte Carlo
      simulations. We analyze real genomic data by using the proposed transformation to
      empirically show how the new methodology allows the variance of these data to be
      stabilized.

PMID- 24133098
TI  - Effects of ventricular insertion sites on rotational motion of left ventricular
      segments studied by cardiac MR.
AB  - OBJECTIVE: Obtaining new details for rotational motion of left ventricular (LV)
      segments using velocity encoding cardiac MR and correlating the regional motion
      patterns to LV insertion sites. METHODS: Cardiac MR examinations were performed
      on 14 healthy volunteers aged between 19 and 26 years. Peak rotational velocities
      and circumferential velocity curves were obtained for 16 ventricular segments.
      RESULTS: Reduced peak clockwise velocities of anteroseptal segments (i.e.
      Segments 2 and 8) and peak counterclockwise velocities of inferoseptal segments
      (i.e. Segments 3 and 9) were the most prominent findings. The observations can be
      attributed to the LV insertion sites into the right ventricle, limiting the
      clockwise rotation of anteroseptal LV segments and the counterclockwise rotation
      of inferoseptal segments as viewed from the apex. Relatively lower clockwise
      velocities of Segment 5 and counterclockwise velocities of Segment 6 were also
      noted, suggesting a cardiac fixation point between these two segments, which is
      in close proximity to the lateral LV wall. CONCLUSION: Apart from showing
      different rotational patterns of LV base, mid ventricle and apex, the study
      showed significant differences in the rotational velocities of individual LV
      segments. Correlating regional wall motion with known orientation of myocardial
      aggregates has also provided new insights into the mechanisms of LV rotational
      motions during a cardiac cycle. ADVANCES IN KNOWLEDGE: LV insertion into the
      right ventricle limits the clockwise rotation of anteroseptal LV segments and the
      counterclockwise rotation of inferoseptal segments adjacent to the ventricular
      insertion sites. The pattern should be differentiated from wall motion
      abnormalities in cardiac pathology.

PMID- 24133099
TI  - Attenuated thermoregulatory, metabolic, and liver acute phase protein response to
      heat stroke in TNF receptor knockout mice.
AB  - Tumor necrosis factor (TNF) is considered an adverse mediator of heat stroke (HS)
      based on clinical studies showing high serum levels. However, soluble TNF
      receptors (sTNFR; TNF antagonists) were higher in survivors than nonsurvivors,
      and TNFR knockout (KO) mice showed a trend toward increased mortality, suggesting
      TNF has protective actions for recovery. We delineated TNF actions in HS by
      comparing thermoregulatory, metabolic, and inflammatory responses between B6129F2
      (wild type, WT) and TNFR KO mice. Before heat exposure, TNFR KO mice showed ~0.4
      degrees C lower core temperature (T(c); radiotelemetry), ~10% lower metabolic
      rate (M(r); indirect calorimetry), and reduced plasma interleukin (IL)-1alpha and
      sIL-1RI than WT mice. KO mice selected warmer temperatures than WT mice in a
      gradient but remained hypothermic. In the calorimeter, both genotypes showed a
      similar heating rate, but TNFR KO maintained lower T(c) and M(r) than WT mice for
      a given heat exposure duration and required ~30 min longer to reach maximum T(c)
      (42.4 degrees C). Plasma IL-6 increased at ~3 h of recovery in both genotypes,
      but KO mice showed a more robust sIL-6R response. Higher sIL-6R in the KO mice
      was associated with delayed liver p-STAT3 protein expression and attenuated serum
      amyloid A3 (SAA3) gene expression, suggesting the acute phase response (APR) was
      attenuated in these mice. Our data suggest that the absence of TNF signaling
      induced a regulated hypothermic state in the KO mice, TNF-IL-1 interactions may
      modulate T(c) and M(r) during homeostatic conditions, and TNF modulates the APR
      during HS recovery through interactions with the liver IL-6-STAT3 pathway of SAA3
      regulation.

PMID- 24133100
TI  - Effects of aging on mineralocorticoid-induced salt appetite in rats.
AB  - This work examined the effects of age on salt appetite measured in the form of
      daily saline (i.e., 0.3 M NaCl) drinking in response to administration of
      deoxycorticosterone acetate (DOCA; 5 mg/kg body wt) using young (4 mo), "middle
      aged" adult (12 mo), and old (30 mo) male Brown Norway rats. Water and sodium
      intakes, excretions, and balances were determined daily. The salt appetite
      response was age dependent with "middle-aged" rats ingesting the most saline
      solution followed in order by young and then old rats. While old rats drank the
      least saline solution, the amounts of saline ingested still were copious and
      comprise an unambiguous demonstration of salt appetite in old rats. Middle-aged
      rats had the highest saline preference ratios of the groups under baseline
      conditions and throughout testing consistent with an increased avidity for sodium
      taste. There were age differences in renal handling of water and sodium that were
      consistent with a renal contribution to the greater saline intakes by middle-aged
      rats. There was evidence of impaired renal function in old rats, but this did not
      account for the reduced saline intakes of the oldest rats. 

PMID- 24133101
TI  - Role of an excitatory preoptic-raphe pathway in febrile vasoconstriction of the
      rat's tail.
AB  - Heat dissipation from the rat's tail is reduced in response to cold and during
      fever. The sympathetic premotor neurons for this mechanism, located in the
      medullary raphe, are under tonic inhibitory control from the preoptic area. In
      parallel with the inhibitory pathway, an excitatory pathway from the rostromedial
      preoptic region (RMPO) to the medullary raphe mediates the vasoconstrictor
      response to cold skin. Whether this applies also to the tail vasoconstrictor
      response in fever is unknown. Single- or a few-unit tail sympathetic nerve
      activity (SNA) was recorded in urethane-anesthetized, artificially ventilated
      rats. Experimental fever was induced by PGE2 injected into the lateral cerebral
      ventricle (50 ng in 1.5 MUl icv) or into the RMPO (0.2 ng in 60 nl); in both
      cases, there was a robust increase in tail SNA and a delayed rise in core
      temperature. Microinjection of glutamate receptor antagonist kynurenate (50 mM,
      120 nl) into the medullary raphe completely reversed the tail SNA response to
      intracerebroventricular or RMPO PGE2 injection. Inhibiting RMPO neurons by
      microinjecting glycine (0.5 M, 60 nl) or the GABAA receptor agonist, muscimol (2
      mM, 30-60 nl), reduced the tail SNA response to PGE2 injected into the same site
      by approximately half. Vehicle injections into the medullary raphe or RMPO were
      without effect. These results suggest that the tail vasoconstrictor response
      during experimental fever depends on a glutamatergic excitatory synaptic relay in
      the medullary raphe and that an excitatory output signal from the RMPO
      contributes to the tail vasoconstrictor response during fever. 

PMID- 24133103
TI  - Termination of Amblyopia Treatment: when to Stop Follow-Up Visits and Risk
      Factors for Recurrence.

PMID- 24133102
TI  - Organ-specific development characterizes circadian clock gene Per2 expression in
      rats.
AB  - To explore developmental changes in circadian organization of central and
      peripheral oscillators, circadian rhythms in clock gene expression were examined
      in 12 organs in transgenic rats carrying a bioluminescence reporter for Per2.
      Organ slices were obtained from different developmental stages starting at
      postnatal day 5 and tissue was cultured for more than 6 days. In addition, four
      organs were examined from embryonic day 20. Robust circadian rhythms in
      bioluminescence were detected in all organs examined. The circadian period in
      vitro was specific to each organ and remained essentially the same during
      development. The circadian peak phase on the first day of culture was
      significantly different not only among organs but also in the same organ. Three
      patterns in circadian phase were detected during development. Thus, during
      development, circadian phase did not change in the suprachiasmatic nucleus,
      adrenal gland, and liver, whereas delay shifts were seen in the pineal, lung,
      heart, kidney, spleen, thymus, and testis. Finally, circadian phase advanced at
      postnatal day 10-15 and subsequently delayed in skeletal muscle and
      stomach.Circadian amplitude also showed developmental changes in several organs.
      These findings indicate that the temporal orders of physiological functions of
      various organs change during development. Such age-dependent and organ-specific
      changes in the phase relationship among circadian clocks most likely reflect
      entrainment to organ-specific time cues at different developmental stages. 

PMID- 24133104
TI  - Physiotherapy based on PNF concept for elderly people after conventional colon
      surgery.
AB  - Aging population, increases the number of major abdominal surgery (MAS) performed
      in the elderly. Main goal of physiotherapy after that surgery is prevention
      postoperative complications and reduction of functional limitation. The aim of
      the study was to asses functional status elderly people after MAS during early
      postoperative physiotherapy. MATERIAL AND METHODS: In a prospective randomized
      study involved 34 patients scheduled for elective MAS, aged 65+. Patients were
      randomly assigned to receive PNF or conventional physiotherapy. The study
      included forced spirometry (FVC, FEV1, PEF) and functional tests (gait speed,
      up&go). Measurements were performed before surgery and the fourth day after
      surgery. Also analyzed age, sex, BMI and the level of postoperative independence
      (postoperative independence scale SAP). Kolmogorow- Smirnow test was used to
      check normal distribution, t-Student was used to check whether two sets of data
      differ significantly, and r-Pearsons for correlations testing. p values <0.05
      were considered significant. RESULTS: After surgery the time of gait speed test
      and up and go test was significant longer in comparison to preoperative value.
      FVC%, FEV1%, PEF% values was decrease. In the PNF group was found significantly
      higher postoperative independence(SAP) and shorter length of stay in hospital
      compared to conventional physiotherapy group. Results of SAP and functional tests
      were significantly positive correlated. CONCLUSIONS: Major abdominal surgery
      decrees efficiency of walking and lung ventilation after 65 year old in early
      postoperative period. Some techniques of the PNF concept used in improving older
      patients after the MAS may favourably affect the postoperative increase
      independence and reduce the time of hospitalization.

PMID- 24133105
TI  - Acinetobacter baumannii nosocomial infections.
AB  - Nosocomial infections caused by strains Acinetobacter baumannii strands are a
      growing clinical problem. The occurrence of multidrug-resistant strands is
      observed and that limits the ways of therapy considerably. The aim of the study
      was to determine the rate of infection and susceptibility spectrum of the species
      Acinetobacter baumannii isolated from patients treated at Maria Sklodowska-Curie
      Memorial Hospital in Zgierz with particular emphasis on surgical wards. MATERIALS
      AND METHODS: The material consisted of Acinetobacter baumannii isolates were
      obtained from samples of materials from patients treated at Maria Sklodowska
      Curie Memorial Hospital in Zgierz from January to December 2011. Isolated
      bacterial strains were cultured at microbiological substrates. Isolates were
      identified to species using the VITEK 2 GN card (bioMerieux) and Vitek 2
      automated system (bioMerieux). Susceptibility towards antibiotics of particular
      strains was determined by the means of AST NO 93 card. In the case of resistance
      towards carbapenem, the MIC was marked by E-test with Mueller Hinton substrate.
      The occurrence of MBL was verified by the means of disc system with Mueller
      Hinton substrate. RESULTS: We have shown that total number of Acinetobacter
      baumannii infections at hospital was 140 (10,31% of total results of cultures).
      Percentage of Acinetobacter baumannii infections at wards: Intensive Care Unit
      48%, Surgical Departments 20%, Internal Diseases Department 16%, Neurology 13%,
      other wards - 3%. The susceptibility percentage of Acinetobacter Baumannii
      against antibiotics: colistin 90%, imipenem 64%, meropenem 43%, ampicillin
      sulbactam 28%, amikacin 27%, gentamicin 24%, cefepime 9%, ceftazidime 7%,
      ciprofloxacin 7% CONCLUSIONS: Acinetobacter baumannii infections are a
      significant proportion of nosocomial infections. Most relate to surgical wards
      and ICUs. Acinetobacter baumannii is resistant against most antibiotics. The
      highest percentage of sensitivity demonstrated for colistin and carbapenems.

PMID- 24133106
TI  - Is age a risk factor of postoperative complications in colorectal cancer?
AB  - Colorectal cancer is the most common malignant neoplasm in elderly with peak of
      incidence in 7. and 8. decade of life. Elderly patients with colorectal cancer
      more often require surgery. Advanced age of patients seems to increase the risk
      of postoperative complications. The aim of the study was to compare the frequency
      of early complications in two groups of patients: under 75 and over 75,
      undergoing elective colorectal cancer surgery. MATERIAL AND METHODS: 440
      consecutive adult patients subjected to colorectal cancer surgery between 08.2006
      to 10.2011 in Oncological Surgery Department, Gdynia Centre of Oncology. Group A
      (over 75 year-of-life): 109 patients, median 79 and group B (up to 75 year-of
      life): 331 patients, median 65. Patients requiring emergency surgery were
      excluded from the study. Postoperative 30-day mortality, anastomotic leakage,
      wound infection, bowel obstruction, postoperative respiratory and circulatory
      insufficiency were among analyzed complications. RESULTS: Symptomatic disease was
      observed in 81.6% of group A and in 83% of group B. Groups A and B were
      comparable concerning: BMI, gender, tumor staging, rate of curative and
      palliative resections, and duration of hospital stay. Accompanying diseases were
      more common in group A (83% vs 65%; p<0.0002). Early complications occurred in
      21.1% of patients from group A and in 19.9% from group B. The rate of reoperation
      in early perioperative period didn't differ (6.4% vs 5.7%). Features like: age,
      gender, additional illnesses, tumor location and staging did not influence the
      occurrence of perioperative complications. CONCLUSIONS: Age itself is not a risk
      factor for postoperative complications in spite of higher rate of accompanying
      diseases in elderly.

PMID- 24133107
TI  - Therapeutic management of stoma complications in selected patients.
AB  - Stoma complications occur in 21-75% of patients, and 30% of them require redo
      surgery within 10 years after previous surgical treatment. Medical treatment is
      successful in most cases with no need for surgery. However, severe stoma
      complications are the real challenge for medical team and require an individual
      approach to each patient. The aim of the study was to report stoma patients with
      severe complications of both ileo- and/or colostomy and present different options
      of medical treatment. MATERIAL AND METHODS: Between March 2005 and April 2007 we
      treated 8 patients with severe stoma complications at the Department of General
      and Colorectal Surgery, Medical University of Lodz. There were 4 patients with
      colostomy, 3 patients with ileostomy and one patient with both ileo- and
      colostomy. The mean age of patients was 56,7 years (range 30-68 years). RESULTS:
      In all patients we achieved either complete stoma-related wound healing or we
      observed substantial progress of wound healing with medical treatment. No patient
      required surgery for stoma complications. CONCLUSIONS: Stoma complications still
      occur in spite of adherence to rules of stoma care and surgical technique. Most
      of them can be treated conservatively. Much emphasis is put on close team work
      comprising doctors and nurses in the treatment of severe stoma complications.

PMID- 24133108
TI  - Laparoscopically assisted ileo-colonic resection in patients with Crohn's disease
      -preliminary report.
AB  - Despite increasing number of reports indicating good treatment outcomes,
      laparoscopic treatment of Crohn's disease remains controversial. The aim of the
      study was to compare outcomes of laparoscopically assisted and open ileo-colonic
      resection in patients with active Crohn's disease. MATERIAL AND METHODS: 82
      patients who underwent surgical treatment (44 laparoscopic and 38 open
      procedures) at the Department of General, Oncological and Gastrointestinal
      Surgery in Warsaw were enrolled to the study. The following perioperative
      parameters were compared in both these groups: duration of hospitalization and
      presence of postoperative complications in at least 12 months of follow-up.
      RESULTS: The conversion rate in the laparoscopy group was 29.5%. There were no
      statistically significant differences between the study groups with regard to
      duration of the surgical procedure, requirement for perioperative transfusions
      and total number of postoperative complications (19.3% in the laparoscopy group
      versus 28.9% in the open surgery group). However, amount of analgesic drugs
      required in the postoperative period was significantly lower (25 +/- 6 vs 43 +/-
      9, p < 0.01) and duration of hospitalization was significantly shorter (9.0 vs
      11.3 days, p = 0.021) after laparoscopic versus open procedures procedures. Most
      of the patients with complicated Crohn's disease who were qualified to
      laparoscopic treatment, underwent successful treatment using this method.
      Patients in whom conversion was done, were more likely to be on long term
      preoperative immunosuppressive therapy versus other patients. CONCLUSIONS:
      Laparoscopy is a demanding procedure from the technical point of view, but
      provides valuable benefits to patients with Crohn's disease, including those with
      a complicated disease. However, this method requires ongoing improvement of
      technical aspects and thorough analysis of failures to identify factors that
      could accurately select patients with indications and contraindications to this
      procedure.

PMID- 24133109
TI  - Surgical cost of care in Crohn's disease.
AB  - The aim of the study was to evaluate the cost of surgical care and short-term
      outcomes of Crohn's disease(CD) in the era of laparoscopy and biologic therapy.
      MATERIAL AND METHODS: Review of a prospective database identified CD patients
      that underwent surgical management. Patients were stratified into laparoscopic,
      open, and converted approaches. Main outcome measures were short-term patient
      outcomes and cost of care by approach. RESULTS: 92 patients were analyzed- 63.1%
      laparoscopic, 32.6% open, 4.3% converted. The majority was elective (100%
      converted, 94.8% laparoscopic, 90% open) and segmental resections (75% converted,
      70.7% laparoscopic, 43.3% open). Operative times were similar between
      laparoscopic and open (152 minutes and 138 minutes, respectively). More open
      patients required ICU care (20% versus 12.1% laparoscopic and 0% converted). The
      median LOS was 3 (1-25) days laparoscopic, 4 (1-29) open and 4 (3-8) converted.
      The laparoscopic complication rate was 15.5%, readmission rate 12.1%, and
      reoperation rate 8.6%. The mean total hospital cost was $9,702 laparoscopic,
      $10,782 open, and $13,293 for converted cases (US Dollars). CONCLUSIONS:
      Laparoscopy is appropriate for most CD cases. When necessary to combine with open
      surgery, this results in efficient and effective patient outcomes and healthcare
      utilization. These results are important when weighing the cost of ongoing
      medical therapy versus surgical intervention.

PMID- 24133110
TI  - A case of portomesenteric venous gas detected on computed tomography.
AB  - Portomesenteric vein gas is a rare condition, which pathogenesis is not completly
      understood. One of causes is e.g. mesenteric ischemia. Pathogenesis of this
      condition are: intraabdominal sepsis, interventional procedures, liver
      transplantation, Crohn disease and trauma. In 15% of causes its idiopathic.
      Hepatic portal venous gas predict high risk of mortality (>50%). An advanced
      radiology techniques such as computed tomography can be helpful in recognizing of
      this pathology stage. We want to report a case of 83-year-old man with acute
      abdominal pain after cardiovascular procedure, with portomesenteric vein gas and
      bowel pneumatosis detected on computed tomography.

PMID- 24133111
TI  - Myositis ossificans of the quadriceps femoris mimicking sarcoma as a diagnostic
      and therapeutic problem--case report and literature review.
AB  - Myositis ossificans (MO) may be included in the group of lesions described as
      pseudosarcomas. Its clinical and histological picture frequently mimics a
      malignant neoplasm and therefore, ultimate diagnosis and implementation of
      adequate treatment requires the cooperation of interdisciplinary team of
      physicians. The paper presents the case of 20-year old female patient suffering
      from severe pain in the right thigh. The patient was initially diagnosed with the
      lower limb overload. Rest and administration of non-steroidal anti-inflammatory
      drugs (NSAID) were recommended. Due to the lack of the efficacy of the
      recommended conservative treatment and detection of tumorous mass on ultrasound
      examination, the patient was referred to the cancer centre. The diagnostic
      procedures were extended and an open biopsy of the lesion was performed which
      revealed the presence of MO. The patient underwent a surgical procedure during
      which the pathological mass was entirely removed. Follow up examinations
      conducted upon the conclusion of the rehabilitation indicate no pathologies in
      the operated area.

PMID- 24133112
TI  - Diagnosis and treatment of primary hyperhidrosis.

PMID- 24133113
TI  - Polish consensus on treatment of gastric cancer; update 2013.

PMID- 24133114
TI  - Comparison of contrast-enhanced ultrasonography with grey-scale ultrasonography
      and contrast-enhanced computed tomography in diagnosing focal fatty liver
      infiltrations and focal fatty sparing.
AB  - PURPOSE: Fatty liver infiltrations and fatty sparing impair diagnostic
      performance of grey-scale ultrasonography in differentiating malignant and benign
      focal liver lesions. In the study, we present our experience in diagnosing focal
      fatty liver infiltrations and focal fatty sparing with contrastenhanced
      ultrasonography (CEUS) in comparison to grey-scale ultrasonography and contrast
      enhanced computed tomography (CECT). MATERIAL AND METHOD: The retrospective study
      group (n=82 patients), included 44 (53.7%) men, 38 (46.3%) women (aged 29- 81
      years, mean 55.8 years) with 48 focal fatty liver infiltrations and 34 focal
      fatty sparing. All patients underwent grey-scale ultrasonography (US), CEUS using
      SonoVue(r) and CECT executed within the 7 days. RESULTS: With US, CEUS and CECT
      focal fatty liver infiltrations were diagnosed in 22, 46 and 44 cases,
      respectively. The following values were obtained: sensitivity - 45.8%, 95.8% and
      91.7%, specificity - 100% for all, accuracy - 95.2%, 99.6% and 99.3%,
      respectively. Focal fatty sparing was diagnosed in 16, 31 and 30 cases,
      respectively. The following values were obtained: sensitivity - 47.1%, 91.2% and
      88.2%, specificity - 99.8%, 100% and 100%, accuracy - 95.6%, 99.4% and 99.3%,
      respectively. No statistically significant differences were found in sensitivity
      of diagnosing focal fatty liver infiltrations and focal fatty liver sparing
      between CEUS and CECT. Sensitivity of grey-scale ultrasonography was
      significantly lower when compared to those of CEUS and CECT (p<0.001).
      CONCLUSION: CEUS is as sensitive as CECT in focal fatty infiltrations and focal
      fatty sparing diagnosing. However, CEUS provides more information than CECT about
      the vasculature and enhancement pattern of focal fatty liver infiltrations.

PMID- 24133115
TI  - The contribution of British general practice to our knowledge of epilepsy and its
      effects on people.
AB  - INTRODUCTION: British general practice is a good base for epidemiological
      research which is evidenced by the study of epilepsy. SOURCES OF DATA: A
      comprehensive search of PubMed using various keywords for articles on epilepsy
      research performed in British general practice. AREAS OF AGREEMENT: Studies in
      the setting of general practice have contributed significantly to knowledge in
      the field of epilepsy, especially in relation to epidemiology, studies of
      prognosis and treatment patterns and psychosocial aspects. AREAS OF CONTROVERSY:
      The extent to which epilepsy can be managed in general practice. GROWING POINTS:
      The importance of primary care research and the importance of collaborative
      studies between general practice, hospital and university departments. AREAS
      TIMELY FOR DEVELOPING RESEARCH: The effects of interventions at general practice
      level on seizure control, morbidity and mortality.

PMID- 24133116
TI  - Activation of the cAMP/PKA pathway induces UT-A1 urea transporter
      monoubiquitination and targets it for lysosomal degradation.
AB  - Regulation of urea transporter UT-A1 in the kidney is important for the urinary
      concentrating mechanism. We previously reported that activation of the cAMP/PKA
      pathway by forskolin (FSK) leads to UT-A1 ubiquitination, endocytosis, and
      degradation. In this study, we discovered that FSK-induced UT-A1 ubiquitination
      is monoubiquitination as judged by immunoblotting with specific ubiquitin
      antibodies to the different linkages of the ubiquitin chain. UT-A1
      monoubiquitination induced by FSK was processed mainly on the cell plasma
      membrane. Monoubiquitination facilitates UT-A1 endocytosis, and internalized UT
      A1 is accumulated in the early endosome. Inhibition of ubiquitination by E1
      ubiquitin-activating enzyme inhibitor PYR-41 significantly reduced FSK-induced UT
      A1 endocytosis and degradation. Interestingly, FSK-stimulated UT-A1 degradation
      occurs through a lysosomal protein degradation system. We further found that the
      PKA phosphorylation sites of UT-A1 at Ser486 and Ser499 are required for FSK
      induced UT-A1 monoubiquitination. The physiological significance was confirmed
      using rat kidney inner medullary collecting duct suspensions, which showed that
      vasopressin treatment promotes UT-A1 ubiquitination. We conclude that unlike
      under basal conditions in which UT-A1 is subject to polyubiquitination and
      proteasome-mediated protein degradation, activation of UT-A1 by FSK induces UT-A1
      monoubiquitination and protein lysosomal degradation. 

PMID- 24133117
TI  - Genetics of hypertension: discoveries from the bench to human populations.
AB  - Hypertension is a complex trait that is influenced by both heritable and
      environmental factors. The search for genes accounting for the susceptibility to
      hypertension has driven parallel efforts in human research and in research using
      experimental animals in controlled environmental settings. Evidence from rodent
      models of genetic hypertension and human Mendelian forms of hypertension and
      hypotension have yielded mechanistic insights into the pathways that are
      perturbed in blood pressure homeostasis, most of which converge at the level of
      renal sodium reabsorption. However, the bridging of evidence from these very
      diverse approaches to identify mechanisms underlying hypertension susceptibility
      and the translation of these findings to human populations and public health
      remain a challenge. Furthermore, findings from genome-wide association studies
      still require functional validation in experimental models. In this review, we
      highlight results and implications from key studies in experimental and clinical
      hypertension to date.

PMID- 24133118
TI  - Intravenous renal cell transplantation with SAA1-positive cells prevents the
      progression of chronic renal failure in rats with ischemic-diabetic nephropathy.
AB  - Diabetic nephropathy, the most common cause of progressive chronic renal failure
      and end-stage renal disease, has now reached global proportions. The only means
      to rescue diabetic patients on dialysis is renal transplantation, a very
      effective therapy but severely limited by the availability of donor kidneys.
      Hence, we tested the role of intravenous renal cell transplantation (IRCT) on
      obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and
      diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of
      the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS
      male tubular cells was given intravenously at 15 and 20 wk of age. Rats were
      euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong
      and long-lasting beneficial effects on renal function and structure, including
      tubules and glomeruli. However, donor cells were found engrafted only in renal
      tubules 14 wk after the second infusion. The results indicate that IRCT with
      serum amyloid A-positive cells is effective in preventing the progression of
      chronic kidney disease in rats with diabetic and ischemic nephropathy. 

PMID- 24133119
TI  - Ischemia-reperfusion induces renal tubule pyroptosis via the CHOP-caspase-11
      pathway.
AB  - The apoptotic or necrotic death of renal tubule epithelial cells is the main
      pathogenesis of renal ischemia-reperfusion-induced acute kidney injury (AKI).
      Pyroptosis is a programmed cell death pathway that depends on the activation of
      the caspase cascade and IL-1 cytokine family members. However, the role of
      pyroptosis in AKI induced by ischemia-reperfusion remains unclear. In this study,
      we found that the levels of the pyroptosis-related proteins, including caspase-1,
      caspase-11, and IL-1beta, were significantly increased after 6 h of renal
      ischemia-reperfusion injury (IRI) and peaked at 12 h after IRI. Enhanced
      pyroptosis was accompanied by elevated renal structural and functional injury.
      Similarly, hypoxia-reoxygenation injury (HRI) also induced pyroptosis in renal
      tubule epithelial NRK-52E cells, which was characterized by increased pore
      formation and elevated lactate dehydrogenase release. In addition, obvious
      upregulation of the endoplasmic reticulum (ER) stress biomarkers glucose
      regulated protein 78 and C/EBP homologous protein (CHOP) preceded the incidence
      of pyroptosis in cells treated with IRI or HRI. Pretreatment with a low dose of
      tunicamycin, an inducer of ER stress, relieved IRI-induced pyroptosis and renal
      tissue injury. Silencing of CHOP by small interfering RNA significantly decreased
      HRI-induced pyroptosis of NRK-52E cells, as evidenced by reduced caspase-11
      activity and IL-1beta generation. Therefore, we conclude that pyroptosis of renal
      tubule epithelial cells is a key event during IRI and that CHOP-caspase-11
      triggered by overactivated ER stress may be an essential pathway involved in
      pyroptosis.

PMID- 24133120
TI  - Vasopressin induces apical expression of caveolin in rat kidney collecting duct
      principal cells.
AB  - Caveolin (Cav)1 is expressed in the basolateral membrane domain of renal
      collecting duct (CD) principal cells (PCs), where it is associated with caveolae.
      To reveal any potential involvement of Cav1 in vasopressin signaling, we used
      specific monoclonal and polyclonal antibodies to examine its localization in CD
      PCs of Brattleboro (BB) rats treated with vasopressin (DDAVP). Compared with
      controls, immunofluorescence revealed a time-dependent increase in Cav1
      expression in the apical membrane domain of PCs, where it overlapped with
      aquaporin-2 (AQP2). After 24 h of DDAVP treatment, Cav1 was visible as an
      increased number of small apical spots. The staining gradually became more
      extensive, and, after 2 wk of DDAVP, it occupied the majority of the apical
      membrane domain of many PCs. Cav1 also assumed an apical localization in PCs of
      DDAVP-treated Sprague-Dawley and Long-Evans rats. Similarly, Cav2 appeared at the
      apical pole of PCs after DDAVP treatment of BB, Sprague-Dawley, and Long-Evans
      rats. Immunogold electron microscopy confirmed bipolar Cav1 membrane expression
      in DDAVP-treated BB rats, whereas caveolae were only detected on the basolateral
      membrane. Immunoblot analysis of BB rat whole kidney homogenates revealed no
      significant increase in Cav1 levels in DDAVP-treated rats, suggesting that DDAVP
      induces Cav1 relocalization or modifies its targeting. We conclude that Cav1 and
      Cav2 trafficking and membrane localization are dramatically altered by the action
      of DDAVP. Importantly, the absence of apical caveolae indicates that while Cavs
      may have an as yet undetermined role in vasopressin-regulated signaling
      processes, this is probably unrelated to AQP2 internalization by caveolae. 

PMID- 24133126
TI  - General practice 8 till 8.

PMID- 24133122
TI  - Regulation of NKCC2 activity by inhibitory SPAK isoforms: KS-SPAK is a more
      potent inhibitor than SPAK2.
AB  - The cation cotransporters Na(+)-K(+)-2Cl(-) cotransporter 1 and 2 (NKCC1 and
      NKCC2) and Na(+)-Cl cotransporter (NCC) are phosphorylated and activated by the
      kinases Ste20-related proline alanine-rich kinase (SPAK) and oxidative stress
      responsive kinase (OSR1), and their targeted disruption in mice causes phenotypes
      resembling the human disorders Bartter syndrome and Gitelman syndrome, reflecting
      reduced NKCC2 and NCC activity, respectively. We previously cloned a kinase
      inactive kidney-specific SPAK isoform, kidney-specific (KS)-SPAK, which lacks the
      majority of the kinase domain present in full-length SPAK. Another putative
      inactive SPAK isoform, SPAK2, which only lacks the initial portion of the kinase
      domain, is also highly expressed in kidney. The functional relevance of inactive
      SPAK isoforms is unclear. Here, we tested whether KS-SPAK and SPAK2
      differentially affect cation cotransporter activity. While KS-SPAK and SPAK2 both
      strongly inhibited NKCC1 activity, SPAK2 was a much weaker inhibitor of NKCC2
      activity. Removal of the catalytic loop from SPAK2 resulted in an inhibitory
      effect on NKCC2 similar to that of KS-SPAK. Full-length SPAK is phosphorylated
      and activated by members of the with-no-lysine[K] (WNK) kinase family. Mutation
      of a WNK phosphorylation in KS-SPAK did not alter its ability to inhibit NKCC2
      activity. In contrast, we found that residues involved in KS-SPAK interactions
      with cation cotransporters are required for it to inhibit cotransporter activity.
      Finally, both KS-SPAK and SPAK2 associated with NKCC2, as demonstrated by
      coimmunoprecipitation. Together, these data identify the structural basis for the
      differential effects of KS-SPAK and SPAK2 on cation cotransporter activity that
      may be physiologically important. 

PMID- 24133127
TI  - Radiograph showing the soft tissues of the neck: lateral view.

PMID- 24133121
TI  - Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in
      rabbit renal proximal tubules.
AB  - The renal proximal tubule (PT) is a major site for maintaining whole body pH
      homeostasis and is responsible for reabsorbing ~80% of filtered HCO3(-), the
      major plasma buffer, into the blood. The PT adapts its rate of HCO3(-)
      reabsorption (JHCO3(-)) in response to acute acid-base disturbances. Our
      laboratory previously showed that single isolated perfused PTs adapt JHCO3(-) in
      response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3(-)
      concentrations but, surprisingly, not to pH. The response to CO2 concentration
      can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the
      present study, we exposed enriched rabbit PT suspensions to five acute acid-base
      disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific
      antibodies to determine the influence of each disturbance on pan-pY, ErbB1
      specific pY (four sites), and ErbB2-specific pY (two sites). We found that each
      acid-base treatment generated a distinct temporal pY pattern. For example, the
      summated responses of the individual ErbB1/2-pY sites to each disturbance showed
      that metabolic acidosis (normal CO2 concentration and reduced HCO3(-)
      concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas
      metabolic alkalosis produced a transient increase. Respiratory acidosis (normal
      HCO3(-) concentration and elevated CO2 concentration) had little effect on
      summated pY at 5 min but produced an elevation at 20 min, whereas respiratory
      alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in
      the PT respond to acute acid-base disturbances, consistent with the hypothesis
      that they are part of the signaling cascade. 

PMID- 24133128
TI  - Clare Gerada: best move was "getting into drugs".

PMID- 24133129
TI  - Devices and desires: industry fights toughening of medical device regulation in
      Europe.

PMID- 24133130
TI  - CEO pay at US non-profit hospitals not associated with quality or charity care,
      study finds.

PMID- 24133131
TI  - Ethyl glucuronide (EtG): better than breathalyser or self-reports to detect
      covert short-term relapses into drinking.
AB  - AIMS: The assessment of relapses is widely used as an outcome measure of alcohol
      dependence treatment. However, the methods of assessing relapses range from
      questionnaires to biological markers of alcohol for different time spans. The aim
      of this study was to compare the relapse rates of weekend home stays during long
      term alcohol dependence treatment, assessed by ethyl glucuronide (EtG), breath
      alcohol tests and self-reports. METHODS: Two hundred and ninety-seven alcohol
      dependent patients receiving a long-term inpatient treatment programme
      participated. After a weekend at home (Friday to Sunday) they were evaluated for
      relapse by personal interviews and with breath alcohol tests. A concomitantly
      collected urine sample was later assessed for EtG with liquid chromatography
      tandem mass spectrometry (LC-MS/MS analysis). RESULTS: Of the total, 37.7% of the
      patients were positive for EtG at least once. Breath alcohol tests had been
      positive in only 4.4% and in personal interviews only 5.7% of the patients had
      admitted relapse. 15.6% of EtG tests were positive, but breath alcohol tests were
      negative (Cohen's kappa = 0.056). Ninety-three per cent of the relapses were only
      detected by EtG. CONCLUSION: In addition to breath alcohol tests and interviews,
      urinary EtG can clearly improve the verification of relapse in inpatient
      treatment programmes allowing for weekend stays at home. Without EtG testing, a
      high amount of relapses will stay undetected.

PMID- 24133137
TI  - Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil
      functions.
AB  - Neutrophils play a major role in inflammatory responses and immune defense
      against pathogens. Even though expression of inhibitory receptors has been
      reported on neutrophils, their role remains poorly defined. Here we show that
      primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4)
      inhibitory receptor and that this expression was induced during differentiation
      of the myelomonoblast PLB-985 cell line into "neutrophil-like" cells. Functional
      assays indicated that human leukocyte antigen G, the preferred ligand of ILT4,
      inhibited the phagocytic function of neutrophils. ILT4 engagement also impaired
      reactive oxygen species production induced through CD32a and both receptors were
      found colocalized into neutrophil lipid rafts. Moreover, neutrophil degranulation
      induced through inflammatory stimuli increased ILT4 expression as a result of the
      rapid translocation of an intracellular pool to the cell surface. Consequently to
      this ILT4 up-regulation, the human leukocyte antigen G-mediated inhibition of
      neutrophil phagocytic function was enhanced. Finally, we found that ILT4 up
      regulation induced on healthy donor neutrophils following stimulation was
      impaired in presence of plasma from patients with sepsis. Similarly, ILT4 up
      regulation was inhibited in neutrophils from septic patients. Altogether, our
      results reveal a unique mechanism of regulation of neutrophil functions through
      ILT4 and its exocytosis that may have implications in inflammatory disorders. 

PMID- 24133138
TI  - Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin
      receptor-like kinase 1 during development and cancer progression.
AB  - Lymphatic vessels (LVs) play critical roles in the maintenance of fluid
      homeostasis and in pathological conditions, including cancer metastasis. Although
      mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone
      morphogenetic protein (BMP) receptor family, have been linked to hereditary
      hemorrhagic telangiectasia, a human vascular disease, the roles of activin
      receptor-like kinase 1 (ALK-1) signals in LV formation largely remain to be
      elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were
      enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of
      ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured
      lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited
      enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and
      tumorigenesis. BMP-9 downregulated the expression of the transcription factor
      prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial
      cell identity. Furthermore, silencing prospero-related homeobox 1 expression
      inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique
      molecular basis for the physiological and pathological roles of BMP-9/ALK-1
      signals in LV formation. 

PMID- 24133139
TI  - Fast structural responses of gap junction membrane domains to AB5 toxins.
AB  - Gap junctions (GJs) represent connexin-rich membrane domains that connect
      interiors of adjoining cells in mammalian tissues. How fast GJs can respond to
      bacterial pathogens has not been known previously. Using Bessel beam plane
      illumination and confocal spinning disk microscopy, we found fast (~500 ms)
      formation of connexin-depleted regions (CDRs) inside GJ plaques between cells
      exposed to AB5 toxins. CDR formation appears as a fast redistribution of connexin
      channels within GJ plaques with minor changes in outline or geometry. CDR
      formation does not depend on membrane trafficking or submembrane cytoskeleton and
      has no effect on GJ conductance. However, CDR responses depend on membrane
      lipids, can be modified by cholesterol-clustering agents and extracellular K(+)
      ion concentration, and influence cAMP signaling. The CDR response of GJ plaques
      to bacterial toxins is a phenomenon observed for all tested connexin isoforms.
      Through signaling, the CDR response may enable cells to sense exposure to AB5
      toxins. CDR formation may reflect lipid-phase separation events in the biological
      membrane of the GJ plaque, leading to increased connexin packing and lipid
      reorganization. Our data demonstrate very fast dynamics (in the millisecond-to
      second range) within GJ plaques, which previously were considered to be
      relatively stable, long-lived structures.

PMID- 24133140
TI  - Chromosome missegregation rate predicts whether aneuploidy will promote or
      suppress tumors.
AB  - Aneuploidy, a chromosome content other than a multiple of the haploid number, is
      a common feature of cancer cells. Whole chromosomal aneuploidy accompanying
      ongoing chromosomal instability in mice resulting from reduced levels of the
      centromere-linked motor protein CENP-E has been reported to increase the
      incidence of spleen and lung tumors, but to suppress tumors in three other
      contexts. Exacerbating chromosome missegregation in CENP-E(+/-) mice by reducing
      levels of another mitotic checkpoint component, Mad2, is now shown to result in
      elevated cell death and decreased tumor formation compared with reduction of
      either protein alone. Furthermore, we determine that the additional contexts in
      which increased whole-chromosome missegregation resulting from reduced CENP-E
      suppresses tumor formation have a preexisting, elevated basal level of chromosome
      missegregation that is exacerbated by reduction of CENP-E. Tumors arising from
      primary causes that do not generate chromosomal instability, including loss of
      the INK4a tumor suppressor and microsatellite instability from reduction of the
      DNA mismatch repair protein MLH1, are unaffected by CENP-E-dependent chromosome
      missegregation. These findings support a model in which low rates of chromosome
      missegregation can promote tumorigenesis, whereas missegregation of high numbers
      of chromosomes leads to cell death and tumor suppression. 

PMID- 24133142
TI  - Extension of in vivo half-life of biologically active peptides via chemical
      conjugation to XTEN protein polymer.
AB  - XTEN, unstructured biodegradable proteins, have been used to extend the in vivo
      half-life of genetically fused therapeutic proteins and peptides. To expand the
      applications of XTEN technology to half-life extension of other classes of
      molecules, XTEN protein polymers and methods for chemical XTENylation were
      developed. Two XTEN precursors were engineered to contain enzymatically removable
      purification tags. The proteins were readily expressed in bacteria and purified
      to homogeneity by chromatography techniques. As proof-of-principle, GLP2-2G
      peptide was chemically conjugated to each of the two XTEN protein polymers using
      maleimide-thiol chemistry. The monodisperse nature of XTEN protein polymer
      enabled reaction monitoring as well as the detection of peptide modifications in
      the conjugated state using reverse phase-high performance liquid chromatography
      (RP-HPLC) and electrospray ionization mass spectrometry. The resulting GLP2-2G
      XTEN conjugates were purified by preparative RP-HPLC to homogeneity. In
      comparison with recombinantly fused GLP2-2G-XTEN, chemically conjugated GLP2-2G
      XTEN molecules exhibited comparable in vitro activity, in vitro plasma stability
      and pharmacokinetics in rats. These data suggest that chemical XTENylation could
      effectively extend the half-life of a wide spectrum of biologically active
      molecules, therefore broadening its applicability. 

PMID- 24133143
TI  - Raising more antibodies.

PMID- 24133141
TI  - Cell-cycle regulation of formin-mediated actin cable assembly.
AB  - Assembly of appropriately oriented actin cables nucleated by formin proteins is
      necessary for many biological processes in diverse eukaryotes. However, compared
      with knowledge of how nucleation of dendritic actin filament arrays by the actin
      related protein-2/3 complex is regulated, the in vivo regulatory mechanisms for
      actin cable formation are less clear. To gain insights into mechanisms for
      regulating actin cable assembly, we reconstituted the assembly process in vitro
      by introducing microspheres functionalized with the C terminus of the budding
      yeast formin Bni1 into extracts prepared from yeast cells at different cell-cycle
      stages. EM studies showed that unbranched actin filament bundles were
      reconstituted successfully in the yeast extracts. Only extracts enriched in the
      mitotic cyclin Clb2 were competent for actin cable assembly, and cyclin-dependent
      kinase 1 activity was indispensible. Cyclin-dependent kinase 1 activity also was
      found to regulate cable assembly in vivo. Here we present evidence that formin
      cell-cycle regulation is conserved in vertebrates. The use of the cable
      reconstitution system to test roles for the key actin-binding proteins
      tropomyosin, capping protein, and cofilin provided important insights into
      assembly regulation. Furthermore, using mass spectrometry, we identified
      components of the actin cables formed in yeast extracts, providing the basis for
      comprehensive understanding of cable assembly and regulation. 

PMID- 24133144
TI  - European Union's tobacco products directive.

PMID- 24133145
TI  - Prescribing methylphenidate for moderate ADHD.

PMID- 24133146
TI  - Burden of dengue fever is higher than previously thought.

PMID- 24133149
TI  - Chasing maximal performance: a cautionary tale from the celebrated jumping frogs
      of Calaveras County.
AB  - Maximal performance is an essential metric for understanding many aspects of an
      organism's biology, but it can be difficult to determine because a measured
      maximum may reflect only a peak level of effort, not a physiological limit. We
      used a unique opportunity provided by a frog jumping contest to evaluate the
      validity of existing laboratory estimates of maximum jumping performance in
      bullfrogs (Rana catesbeiana). We recorded video of 3124 bullfrog jumps over the
      course of the 4-day contest at the Calaveras County Jumping Frog Jubilee, and
      determined jump distance from these images and a calibration of the jump arena.
      Frogs were divided into two groups: 'rental' frogs collected by fair organizers
      and jumped by the general public, and frogs collected and jumped by experienced,
      'professional' teams. A total of 58% of recorded jumps surpassed the maximum jump
      distance in the literature (1.295 m), and the longest jump was 2.2 m. Compared
      with rental frogs, professionally jumped frogs jumped farther, and the
      distribution of jump distances for this group was skewed towards long jumps.
      Calculated muscular work, historical records and the skewed distribution of jump
      distances all suggest that the longest jumps represent the true performance limit
      for this species. Using resampling, we estimated the probability of observing a
      given jump distance for various sample sizes, showing that large sample sizes are
      required to detect rare maximal jumps. These results show the importance of
      sample size, animal motivation and physiological conditions for accurate maximal
      performance estimates. 

PMID- 24133150
TI  - Launches, squiggles and pounces, oh my! The water-land transition in mangrove
      rivulus (Kryptolebias marmoratus).
AB  - Mangrove rivulus (Kryptolebias marmoratus) are small fusiform teleosts
      (Cyprinodontiformes) with the ability to locomote on land, despite lacking
      apparent morphological adaptations for terrestrial movement. Rivulus will leave
      their aquatic habitat for moist, terrestrial environments when water conditions
      are poor, or, as we show here, to capture terrestrial insects. Specimens were
      conditioned to eat pinhead crickets on one side of their aquaria. After 2 weeks
      of conditioning, a barrier with a slope of 15 deg was partially submerged in the
      middle of the tank, forcing the fish to transition from water to land and back
      into water in order to feed. Kinematics during the transition were recorded using
      Fastec high-speed video cameras (125-250 frames s(-1)). Videos were analyzed
      using Didge and ImageJ software programs. Transition behaviors were characterized
      and analyzed according to their specific type. Body oscillation amplitude and
      wave duration were quantified for movements along the substrate, along with
      initial velocity for launching behaviors. Kryptolebias marmoratus used a diverse
      suite of behaviors to transition from water to land. These behaviors can be
      categorized as launches, squiggles and pounces. Prey were captured terrestrially
      and brought underwater for consumption. Kryptolebias marmoratus's suite of
      behaviors represents a novel solution to non-tetrapodal terrestrial transition,
      which suggests that fishes may have been able to exploit land habitats
      transiently, without leaving any apparent evidence in the fossil record. 

PMID- 24133151
TI  - Complex vibratory patterns in an elephant larynx.
AB  - Elephants' low-frequency vocalizations are produced by flow-induced self
      sustaining oscillations of laryngeal tissue. To date, little is known in detail
      about the vibratory phenomena in the elephant larynx. Here, we provide a first
      descriptive report of the complex oscillatory features found in the excised
      larynx of a 25 year old female African elephant (Loxodonta africana), the largest
      animal sound generator ever studied experimentally. Sound production was
      documented with high-speed video, acoustic measurements, air flow and sound
      pressure level recordings. The anatomy of the larynx was studied with computed
      tomography (CT) and dissections. Elephant CT vocal anatomy data were further
      compared with the anatomy of an adult human male. We observed numerous unusual
      phenomena, not typically reported in human vocal fold vibrations. Phase delays
      along both the inferior-superior and anterior-posterior (A-P) dimension were
      commonly observed, as well as transverse travelling wave patterns along the A-P
      dimension, previously not documented in the literature. Acoustic energy was
      mainly created during the instant of glottal opening. The vestibular folds, when
      adducted, participated in tissue vibration, effectively increasing the generated
      sound pressure level by 12 dB. The complexity of the observed phenomena is partly
      attributed to the distinct laryngeal anatomy of the elephant larynx, which is not
      simply a large-scale version of its human counterpart. Travelling waves may be
      facilitated by low fundamental frequencies and increased vocal fold tension. A
      travelling wave model is proposed, to account for three types of phenomena: A-P
      travelling waves, 'conventional' standing wave patterns, and irregular vocal fold
      vibration. 

PMID- 24133152
TI  - Nasal sound production in echolocating delphinids (Tursiops truncatus and
      Pseudorca crassidens) is dynamic, but unilateral: clicking on the right side and
      whistling on the left side.
AB  - Toothed whales produce sound in their nasal complex by pneumatic actuation of
      phonic lip pairs within the blowhole. It has been hypothesized that dual
      actuation of the phonic lip pairs can generate two pulses that merge to form a
      single echolocation click with a higher source level, broader bandwidth and
      larger potential for beam steering than if produced by a single pair of phonic
      lips. Here, we test that hypothesis by measuring the sound production of five
      echolocating delphinids using hydrophones around the animals and imbedded in on
      animal suction cups. We show that the studied animals click with their right pair
      of phonic lips and whistle with their left pair. We demonstrate that, with just a
      single pair of phonic lips, they can change the click energy levels over five
      orders of magnitude, change the click centroid frequencies over more than two
      octaves, and modulate the sound radiation from the melon for beam steering. We
      conclude that all of the click dynamics ascribed to dual actuation of two phonic
      lip pairs can be achieved with actuation of just the right pair of phonic lips,
      and we propose that the large dynamic range of source outputs is achieved by
      highly controlled modulation of the pneumatic driving pressure, the tension of
      the phonic lip labia and the conformation of the fatty melon and associated air
      sacs. 

PMID- 24133153
TI  - Quantifying energy intake in Pacific bluefin tuna (Thunnus orientalis) using the
      heat increment of feeding.
AB  - Using implanted archival tags, we examined the effects of meal caloric value,
      food type (sardine or squid) and ambient temperature on the magnitude and
      duration of the heat increment of feeding in three captive juvenile Pacific
      bluefin tuna. The objective of our study was to develop a model that can be used
      to estimate energy intake in wild fish of similar body mass. Both the magnitude
      and duration of the heat increment of feeding (measured by visceral warming)
      showed a strong positive correlation with the caloric value of the ingested meal.
      Controlling for meal caloric value, the extent of visceral warming was
      significantly greater at lower ambient temperature. The extent of visceral
      warming was also significantly higher for squid meals compared with sardine
      meals. By using a hierarchical Bayesian model to analyze our data and treating
      individuals as random effects, we demonstrate how increases in visceral
      temperature can be used to estimate the energy intake of wild Pacific bluefin
      tuna of similar body mass to the individuals used in our study. 

PMID- 24133154
TI  - Aversive conditioning in honey bees (Apis mellifera anatolica): a comparison of
      drones and workers.
AB  - Honey bees provide a model system to elucidate the relationship between sociality
      and complex behaviors within the same species, as females (workers) are highly
      social and males (drones) are more solitary. We report on aversive learning
      studies in drone and worker honey bees (Apis mellifera anatolica) in escape,
      punishment and discriminative punishment situations. In all three experiments, a
      newly developed electric shock avoidance assay was used. The comparisons of
      expected and observed responses were performed with conventional statistical
      methods and a systematic randomization modeling approach called object oriented
      modeling. The escape experiment consisted of two measurements recorded in a
      master-yoked paradigm: frequency of response and latency to respond following
      administration of shock. Master individuals could terminate an unavoidable shock
      triggered by a decrementing 30 s timer by crossing the shuttlebox centerline
      following shock activation. Across all groups, there was large individual
      response variation. When assessing group response frequency and latency, master
      subjects performed better than yoked subjects for both workers and drones. In the
      punishment experiment, individuals were shocked upon entering the shock portion
      of a bilaterally wired shuttlebox. The shock portion was spatially static and
      unsignalled. Only workers effectively avoided the shock. The discriminative
      punishment experiment repeated the punishment experiment but included a
      counterbalanced blue and yellow background signal and the side of shock was
      manipulated. Drones correctly responded less than workers when shock was paired
      with blue. However, when shock was paired with yellow there was no observable
      difference between drones and workers. 

PMID- 24133162
TI  - Phylogeographical patterns of an alpine plant, Rhodiola dumulosa (Crassulaceae),
      inferred from chloroplast DNA sequences.
AB  - The phylogeographical patterns of Rhodiola dumulosa, an alpine plant species
      restrictedly growing in the crevices of rock piles, were investigated based on 4
      fragments of the chloroplast genome. To cover the full distribution of R.
      dumulosa in China, 19 populations from 3 major disjunct distribution areas
      (northern, central, and northwestern China) were sampled. A total of 5881bp
      (after alignment) of chloroplast DNA (cpDNA) from 100 individuals were sequenced.
      The combined cpDNA data set yielded 36 haplotypes. The total genetic diversity of
      R. dumulosa was remarkably high (H(T) = 0.981). The interpopulation genetic
      differentiation was significantly large (F(ST) = 0.8537, P < 0.001), possibly due
      to the long-term isolation of the natural populations. N(ST) was significantly
      larger than G(ST) (P < 0.001), indicating the presence of phylogeographical
      structure among the R. dumulosa populations. We propose 2 migration steps to
      explain the current distribution of R. dumulosa in China. First, this species
      migrated from refugia in the Qinghai-Tibetan Plateau to northern areas via the
      intervening highlands when temperatures increased; second, the highland
      populations migrated toward the mountaintops when temperatures increased further
      because R. dumulosa is adapted to cold environments. During the second migration
      step, the common ancestral haplotypes may have been gradually lost.

PMID- 24133165
TI  - The uncoupling of monocyte-platelet interactions from the induction of
      proinflammatory signaling in monocytes.
AB  - Induction of an inflammatory monocyte phenotype by activated platelets is
      implicated in the pathogenesis of inflammatory diseases, including
      atherosclerosis. In this study, we investigated the early signaling events
      associated with this platelet-induced inflammatory phenotype. We report that
      coculture of human monocytes with activated platelets induces phosphorylation of
      Akt, together with rapid mobilization of intracellular Ca(2+), and show that
      these signaling events can be uncoupled from monocyte binding to activated
      platelets. Specifically, Ab-inhibition studies and incubation of monocytes with
      activated platelet supernatant highlighted a role for secreted product(s) of
      activated platelets. We also identified a role for pertussis toxin-sensitive G
      protein-coupled receptors and excluded key candidates platelet-activating factor
      receptor and CCR5. Our results suggest that inhibition of monocyte-platelet
      interactions via PSGL-1 or P-selectin is not sufficient to prevent platelet
      mediated monocyte activation in an inflammatory context. These findings have
      important implications for the development of therapeutics to treat diseases in
      which platelet-monocyte complexes are implicated in pathogenesis. 

PMID- 24133166
TI  - Interaction of CD99 with its paralog CD99L2 positively regulates CD99L2
      trafficking to cell surfaces.
AB  - Mouse CD99 and its paralog CD99-like 2 (CD99L2) are surface proteins implicated
      in cellular adhesion and migration. Although their distributions overlap in a
      wide variety of cells, their physical/functional relationship is currently
      unknown. In this study, we show the interaction between the two molecules and its
      consequence for membrane trafficking of mouse (m)CD99L2. The interaction was
      analyzed by bimolecular fluorescence complementation, immunoprecipitation, and
      fluorescence resonance energy transfer assays. When coexpressed, mCD99 formed
      heterodimers with mCD99L2, as well as homodimers, and the heterodimers were
      localized more efficiently at the plasma membrane than were the homodimers. Their
      interaction was cytoplasmic domain-dependent and enhanced mCD99L2 trafficking to
      the plasma membrane regardless of whether it was transiently overexpressed or
      endogenously expressed. Surface levels of endogenous mCD99L2 were markedly low on
      thymocytes, splenic leukocytes, and CTL lines derived from CD99-deficient mice.
      Importantly, the surface levels of mCD99L2 on mCD99-deficient cells recovered
      significantly when wild-type mCD99 was exogenously introduced, but they remained
      low when a cytoplasmic domain mutant of mCD99 was introduced. Our results
      demonstrate a novel role for mCD99 in membrane trafficking of mCD99L2, providing
      useful insights into controlling transendothelial migration of leukocytes. 

PMID- 24133167
TI  - Tissue LyC6- macrophages are generated in the absence of circulating LyC6-
      monocytes and Nur77 in a model of muscle regeneration.
AB  - There are several open questions regarding the origin, development, and
      differentiation of subpopulations of monocytes, macrophages (MFs), and dendritic
      cells. It is a particularly intriguing question how circulating monocyte subsets
      develop and contribute to the generation of steady-state and inflammatory tissue
      MF pools and which transcriptional mechanisms contribute to these processes. In
      this study, we took advantage of a genetic model in which LyC6(-) circulating
      monocyte development is severely diminished due to the lack of the nuclear
      receptor, NUR77. We show that, in a mouse model of skeletal muscle injury and
      regeneration, the accumulation of leukocytes and the generation of LyC6(+) and
      LyC6(-) MF pools are intact in the absence of circulating LyC6(-) blood
      monocytes. These data suggest that NUR77, which is required for LyC6(-) blood
      monocyte development, is expressed but not critically required for LyC6(+) to
      LyC6(-) tissue MF specification. Moreover, these observations support a model
      according to which tissue macrophage subtype specification is distinct from that
      of circulating monocytes. Lastly, our data show that in the used sterile
      inflammation model tissue LyC6(-) MFs are derived from LyC6(+) cells. 

PMID- 24133168
TI  - IL-13 immunotoxin accelerates resolution of lung pathological changes triggered
      by silica particles in mice.
AB  - Instillation of silica into the lungs of rodents results in pathological changes
      that strongly mimic human silicosis, an occupational lung disease marked by
      restrictive airway obstruction, inflammation, and fibrosis. Because IL-13 is a
      pivotal proinflammatory and fibrogenic cytokine, we examined whether a
      recombinant immunotoxin comprised of human IL-13 and a mutated form of
      Pseudomonas exotoxin (IL-13-PE) might affect pathological features of
      experimental silicosis. Mice received a single intranasal instillation of silica
      particles and were treated with intranasal IL-13-PE every other day from days 21
      to 27 postsilica. The sensitivity of putative cell targets to IL-13-PE was also
      assessed in in vitro settings. Upregulation of IL-13, its receptor subunits IL
      13Ralpha1 and IL-13Ralpha2, and shared receptor IL-4Ralpha were associated with
      development of granulomatous lung inflammation triggered by silica. IL-13-PE
      inhibited silica-induced granuloma and fibrotic responses noted at 24 h and 15 d
      after the last treatment. Upregulation of TNF-alpha, TGF-beta, and chemokines, as
      well as increased collagen deposition and airway hyperreactivity to methacholine
      were all clearly sensitive to IL-13-PE. In addition, IL-13-PE inhibited both IL
      13-induced proliferation of cultured lung fibroblasts from silicotic mice and
      silica-induced IL-8 generation from A549 cells. In conclusion, our findings show
      that therapeutic treatment with IL-13-PE can reverse important pathological
      features caused by inhalation of silica particles, suggesting that this
      recombinant immunotoxin is a promising molecular template in drug discovery for
      the treatment of silicosis. 

PMID- 24133169
TI  - IFN-gamma-induced priming maintains long-term strain-transcending immunity
      against blood-stage Plasmodium chabaudi malaria.
AB  - The mechanism by which protective immunity to Plasmodium is lost in the absence
      of continued exposure to this parasite has yet to be fully elucidated. It has
      been recently shown that IFN-gamma produced during human and murine acute malaria
      primes the immune response to TLR agonists. In this study, we investigated
      whether IFN-gamma-induced priming is important to maintain long-term protective
      immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6
      mice still had chronic parasitemia and efficiently controlled homologous and
      heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented
      numbers of effector/effector memory (TEM) CD4(+) cells, which is associated with
      increased levels of IFN-gamma-induced priming (i.e., high expression of IFN
      inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN
      gamma-induced priming was no longer detected and protective immunity to
      heterologous challenge was mostly lost with >70% mortality. Spontaneously cured
      mice had high serum levels of parasite-specific IgG, but effector T/TEM cell
      numbers, parasite-driven CD4(+) T cell proliferation, and IFN-gamma production
      were similar to noninfected controls. Remarkably, the priming of cured mice with
      low doses of IFN-gamma rescued TLR hyperresponsiveness and the capacity to
      control heterologous challenge, increasing the TEM cell population and restoring
      the CD4(+) T cell responses to parasites. Contribution of TLR signaling to the
      CD4(+) T cell responses in chronic mice was supported by data obtained in mice
      lacking the MyD88 adaptor. These results indicate that IFN-gamma-induced priming
      is required to maintain protective immunity against P. chabaudi and aid in
      establishing the molecular basis of strain-transcending immunity in human
      malaria. 

PMID- 24133175
TI  - Factors impacting variability of the urinary normeperidine-to-meperidine
      metabolic ratio in patients with chronic pain.
AB  - Meperidine (Demerol((r))) is a mu- and kappa-opiate receptor agonist used for
      moderate to severe pain. Overdose can result in respiratory depression,
      hypotension and coma, while accumulation of its toxic metabolite, normeperidine,
      can cause delirium and seizures. Little data exist examining the inter- and
      intrasubject variability of the normeperidine-to-meperidine metabolic ratio (MR)
      in urine. This retrospective data analysis examined meperidine and normeperidine
      urine concentrations collected from chronic pain patients. In 98 subjects with
      multiple visits, the geometric mean urinary MR = 6.1 (coefficient of variation,
      %CV = 68%). From single specimens obtained from 799 subjects, the geometric mean
      urinary MR = 6.2 (%CV = 212%). The urinary MR increased in young subjects
      compared with elderly (P = 0.004) and middle-aged subjects (P = 0.01). A 27%
      difference was found between the male and female urinary MR (male geometric mean
      MR = 5.1, female geometric mean MR = 7.0, P = 0.02). Intersubject variability in
      meperidine metabolism was 3-fold greater than intrasubject variability. A
      significant difference in the urinary MR was found between males and females. The
      substantial variability in meperidine metabolism and the serious side effects of
      its metabolite normeperidine require greater vigilance in patient medication
      monitoring. 

PMID- 24133181
TI  - Epidemiology and clinical presentation of parainfluenza type 4 in children: a 3
      year comparative study to parainfluenza types 1-3.
AB  - BACKGROUND: Human parainfluenza viruses (HPIVs) are among the most common causes
      of respiratory tract infections in children. Little is known about the
      epidemiology and clinical presentation of HPIV type 4. METHODS: A retrospective
      chart review and comparison of patients positive for HPIV types 1-4 by multiplex
      polymerase chain reaction between 2009 and 2012 at Children's Hospital Colorado
      was performed. Patients who had only direct fluorescent antibody testing
      performed or concurrent viral infections were excluded. RESULTS: Of 11,533
      samples, 752 (6.5%) were positive for HPIV. After exclusion criteria, 316 samples
      were included in the study. HPIV-4 had year-round prevalence with biennial peaks
      in odd-numbered years. HPIV-4 and HPIV-3 had similar clinical presentations.
      50.8% and 51.5% of patients with HPIV-3-4 had hypoxia compared to 20.3% and 33.3%
      of patients with HPIV-1-2 (P < .01). HPIV-1 (23.6%) and HPIV-2 (24.2%) were more
      associated with stridor than HPIV-3 (6.6%) and HPIV-4 (0%) (P < .01). No patients
      with HPIV-4 had croup. Patients with HPIV-4 had similar lengths of stay and
      mortality as those with HPIV-1-3. CONCLUSIONS: This is the first large-scale
      analysis of HPIV-4 clinical and epidemiologic features. HPIV-4 was most similar
      to HPIV-3 in clinical presentation. HPIV-4 had year-round prevalence with peaks
      in the autumn of odd-numbered years. HPIV-4 is a common respiratory pathogen
      capable of causing significant morbidity in children.

PMID- 24133182
TI  - Regulatory T cells prevent liver fibrosis during HIV type 1 infection in a
      humanized mouse model.
AB  - Human immunodeficiency virus type 1 (HIV-1) disease is associated with aberrant
      immune activation, and coinfection with hepatitis C virus (HCV) exacerbates
      hepatic inflammation and fibrosis. However, the role of HIV-1 infection or host
      immune modulation in liver pathogenesis is not clearly defined. Here, we report
      that regulatory T (Treg) cells prevent liver immunopathogenesis during HIV-1
      infection in a humanized mouse model. In the absence of Treg cells, HIV-1
      infection induced liver fibrosis associated with hepatic stellate cell
      activation, hepatitis, and liver injury. Our findings provide new insight linking
      Treg cells and liver immunopathogenesis during HIV-1 infection. 

PMID- 24133183
TI  - HIV treatment, preexposure prophylaxis, and drug resistance: reconciling
      conflicting predictions from mathematical models.

PMID- 24133184
TI  - Maternal antibody at delivery protects neonates from early onset group B
      streptococcal disease.
AB  - BACKGROUND: Further reduction in the group B streptococcal (GBS) disease burden
      in neonates in the United States awaits an additional prevention strategy, such
      as maternal immunization. METHODS: We performed a prospective, multicenter, case
      control study of 33 mothers delivering neonates with early onset GBS infection
      (cases), and 99 age- and ethnicity-matched mothers colonized with the same
      capsular polysaccharide (CPS) types delivering healthy neonates (controls).
      Relative risk and absolute risk were calculated for early onset disease
      associated with concentrations of type Ia, III, or V CPS-specific antibody in
      maternal serum. RESULTS: For GBS types Ia and III, maternal CPS-specific antibody
      concentrations of >= 0.5 ug/mL were associated with a relative risk of
      approximately 0.1 (95% confidence intervals [CIs], .01-.74 and 0-.72,
      respectively; P = .02 for each), corresponding to a 90% risk reduction (by
      logistic regression). For type V, the relative risk was 0.3 (95% CI, .01-3.1),
      corresponding to a 70% risk reduction. By Bayesian modeling, the risk of early
      onset disease would decrease by 70% if maternal CPS-specific antibody
      concentrations for these 3 GBS types were >= 1 ug/mL. CONCLUSIONS: Maternal CPS
      specific antibody serum concentrations of >= 1 MUg/mL at the time of delivery
      appear to protect most neonates from early onset GBS type Ia and III disease.

PMID- 24133185
TI  - Macrophages accumulate in the gut mucosa of untreated HIV-infected patients.
AB  - BACKGROUND: Mucosal macrophages are involved in the maintenance of epithelial
      barrier integrity and the elimination of invading pathogens. Although an
      intestinal barrier defect and microbial translocation are hallmarks of human
      immunodeficiency virus (HIV) infection, recent data on gut mucosal macrophages in
      HIV infection are sparse. METHODS: Treatment-naive and treated HIV-infected
      patients and healthy controls were studied for frequencies and functional
      parameters of blood monocytes and macrophages in duodenal mucosa. RESULTS: We
      found mucosal enrichment of macrophages in untreated HIV infection associated
      with reduced monocyte counts in blood and increased monocyte expression of the
      gut-homing molecule integrin beta7. Increased CCR2 density on integrin beta7
      expressing monocytes and mucosal secretion of CCL2 suggest that CCR2/CCL2
      chemotaxis is involved in enhanced trafficking of blood monocytes to the gut.
      Secretion of macrophage-related proinflammatory molecules interleukin 1beta,
      CCL5, CXCL9, and CXCL10 was increased in the gut mucosa of untreated patients.
      Moreover, mucosal macrophages of untreated patients showed reduced phagocytic
      activity. CONCLUSIONS: These data suggest a role for gut mucosal macrophages in
      HIV immune pathogenesis: infiltrated macrophages in the intestinal mucosa may
      promote local inflammation and tissue injury, whereas their low phagocytic
      activity prevents the efficient elimination of luminal antigens that cross the
      damaged intestinal barrier.

PMID- 24133186
TI  - Antiretroviral treatment, preexposure prophylaxis, and drug resistance in sub
      Saharan Africa: a consensus among mathematical models.

PMID- 24133187
TI  - Lack of a therapeutic role for interferon gamma in patients with tuberculosis.

PMID- 24133189
TI  - Reply to Wallis.

PMID- 24133188
TI  - Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte
      binding protein homologue 5 inhibit parasite growth and predict protection from
      malaria.
AB  - BACKGROUND: Plasmodium falciparum reticulocyte-binding protein homologue 5
      (PfRH5) is a blood-stage parasite protein essential for host erythrocyte
      invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in
      vitro, but the relevance of naturally acquired PfRH5-specific antibodies in
      humans is unclear. METHODS: We assessed pre-malaria season PfRH5-specific
      immunoglobulin G (IgG) levels in 357 Malian children and adults who were
      uninfected with Plasmodium. Subsequent P. falciparum infections were detected by
      polymerase chain reaction every 2 weeks and malaria episodes by weekly physical
      examination and self-referral for 7 months. The primary outcome was time between
      the first P. falciparum infection and the first febrile malaria episode. PfRH5
      specific IgG was assayed for parasite growth-inhibitory activity. RESULTS: The
      presence of PfRH5-specific IgG at enrollment was associated with a longer time
      between the first blood-stage infection and the first malaria episode (PfRH5
      seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This
      association remained significant after adjustment for age and other factors
      associated with malaria risk/exposure (hazard ratio, .62; P = .02). Concentrated
      PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro.
      CONCLUSIONS: Naturally acquired PfRH5-specific IgG inhibits parasite growth in
      vitro and predicts protection from malaria. These findings strongly support
      efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine.
      CLINICAL TRIALS REGISTRATION: NCT01322581.

PMID- 24133190
TI  - Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages
      and in mice by enhancing autophagy and phagosome maturation.
AB  - BACKGROUND: Statins are cholesterol-lowering drugs, targeting HMG-CoA reductase,
      thereby reducing the risk of coronary disorders and hypercholesterolemia.
      However, they also can influence immunologic responses. METHODS: Peripheral blood
      mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) were isolated
      from patients with familial hypercholesterolemia (FH) during statin therapy.
      After infection of cells with Mycobacterium tuberculosis, bacterial burden was
      determined. In vivo, mice were treated with statins before aerosol-based
      infection with M. tuberculosis and were monitored for disease progression.
      RESULTS: PBMCs and MDMs from patients with FH receiving statin therapy were more
      resistant to M. tuberculosis infection, with reduced bacterial burdens, compared
      with those of healthy donors. Moreover, statin treatment in experimental murine
      M. tuberculosis infection studies increased host protection, with reduced lung
      burdens and improved histopathologic findings. Mechanistically, metabolic rescue
      experiments demonstrated that statins reduce membrane cholesterol levels,
      particularly by the mevalonate-isoprenoid arm of the sterol pathway. This
      promoted phagosomal maturation (EEA-1/Lamp-3) and autophagy (LC3-II), as shown by
      confocal microscopy and Western blot in macrophages. In addition, inhibitors of
      phagosome and autophagosome maturation reversed the beneficial effect of statins
      on bacterial growth. CONCLUSION: These results suggest that statin-mediated
      reduction in cholesterol levels within phagosomal membranes counteract M.
      tuberculosis-induced inhibition of phagosomal maturation and promote host-induced
      autophagy, thereby augmenting host protection against tuberculosis.

PMID- 24133192
TI  - What's Your Diagnosis?

PMID- 24133191
TI  - The neuraminidase inhibitor oseltamivir is effective against A/Anhui/1/2013
      (H7N9) influenza virus in a mouse model of acute respiratory distress syndrome.
AB  - BACKGROUND:  High mortality and uncertainty about the effectiveness of
      neuraminidase inhibitors (NAIs) in humans infected with influenza A(H7N9) viruses
      are public health concerns. METHODS:  Susceptibility of N9 viruses to NAIs was
      determined in a fluorescence-based assay. The NAI oseltamivir (5, 20, or 80
      mg/kg/day) was administered to BALB/c mice twice daily starting 24, 48, or 72
      hours after A/Anhui/1/2013 (H7N9) virus challenge. RESULTS:  All 12 avian N9 and
      3 human H7N9 influenza viruses tested were susceptible to NAIs. Without prior
      adaptation, A/Anhui/1/2013 (H7N9) caused lethal infection in mice that was
      restricted to the respiratory tract and resulted in pulmonary edema and acute
      lung injury with hyaline membrane formation, leading to decreased oxygenation,
      all characteristics of human acute respiratory distress syndrome. Oseltamivir at
      20 and 80 mg/kg protected 80% and 88% of mice when initiated after 24 hours, and
      the efficacy decreased to 70% and 60%, respectively, when treatment was delayed
      by 48 hours. Emergence of oseltamivir-resistant variants was not detected.
      CONCLUSIONS:  H7N9 viruses are comparable to currently circulating influenza A
      viruses in susceptibility to NAIs. Based on these animal studies, early treatment
      is associated with improved outcomes.

PMID- 24133193
TI  - Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm.
AB  - We investigated the prostaglandin (PG)E2 pathway in human abdominal aortic
      aneurysm (AAA) and its relationship with hypervascularization. We analyzed
      samples from patients undergoing AAA repair in comparison with those from healthy
      multiorgan donors. Patients were stratified according to maximum aortic diameter:
      low diameter (LD) (<55 mm), moderate diameter (MD) (55-69.9 mm), and high
      diameter (HD) (>=70 mm). AAA was characterized by abundant microvessels in the
      media and adventitia with perivascular infiltration of CD45-positive cells. Like
      endothelial cell markers, cyclooxygenase (COX)-2 and the microsomal isoform of
      prostaglandin E synthase (mPGES-1) transcripts were increased in AAA (4.4- and
      1.4-fold, respectively). Both enzymes were localized in vascular cells and
      leukocytes, with maximal expression in the LD group, whereas leukocyte markers
      display a maximum in the MD group, suggesting that the upregulation of COX
      2/mPGES-1 precedes maximal leukocyte infiltration. Plasma and in vitro tissue
      secreted levels of PGE2 metabolites were higher in AAA than in controls (plasma
      controls, 19.9 +/- 2.2; plasma-AAA, 38.8 +/- 5.5 pg/ml; secretion-normal aorta,
      16.5 +/- 6.4; secretion-AAA, 72.9 +/- 6.4 pg/mg; mean +/- SEM). E-prostanoid
      receptor (EP)-2 and EP-4 were overexpressed in AAA, EP-4 being the only EP
      substantially expressed and colocalized with mPGES-1 in the microvasculature.
      Additionally, EP-4 mediated PGE2-induced angiogenesis in vitro. We provide new
      data concerning mPGES-1 expression in human AAA. Our findings suggest the
      potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated
      hypervascularization. 

PMID- 24133194
TI  - DHA attenuates postprandial hyperlipidemia via activating PPARalpha in intestinal
      epithelial cells.
AB  - It is known that peroxisome proliferator-activated receptor (PPAR)alpha, whose
      activation reduces hyperlipidemia, is highly expressed in intestinal epithelial
      cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia,
      however, its relationship with intestinal PPARalpha activation is not revealed.
      In this study, we investigated whether DHA can affect postprandial hyperlipidemia
      by activating intestinal PPARalpha using Caco-2 cells and C57BL/6 mice. The genes
      involved in fatty acid (FA) oxidation and oxygen consumption rate were increased,
      and the secretion of triacylglyceride (TG) and apolipoprotein B (apoB) was
      decreased in DHA-treated Caco-2 cells. Additionally, intestinal FA oxidation was
      induced, and TG and apoB secretion from intestinal epithelial cells was reduced,
      resulting in the attenuation of plasma TG and apoB levels after oral
      administration of olive oil in DHA-rich oil-fed mice compared with controls.
      However, no increase in genes involved in FA oxidation was observed in the liver.
      Furthermore, the effects of DHA on intestinal lipid secretion and postprandial
      hyperlipidemia were abolished in PPARalpha knockout mice. In conclusion, the
      present work suggests that DHA can inhibit the secretion of TG from intestinal
      epithelial cells via PPARalpha activation, which attenuates postprandial
      hyperlipidemia. 

PMID- 24133203
TI  - 3q27.3 microdeletional syndrome: a recognisable clinical entity associating
      dysmorphic features, marfanoid habitus, intellectual disability and psychosis
      with mood disorder.
AB  - BACKGROUND: Since the advent of array-CGH, numerous new microdeletional syndromes
      have been delineated while others remain to be described. Although 3q29
      subtelomeric deletion is a well-described syndrome, there is no report on 3q
      interstitial deletions. METHODS: We report for the first time seven patients with
      interstitial deletions at the 3q27.3q28 locus gathered through the Decipher
      database, and suggest this locus as a new microdeletional syndrome. RESULTS: The
      patients shared a recognisable facial dysmorphism and marfanoid habitus,
      associated with psychosis and mild to severe intellectual disability (ID). Most
      of the patients had no delay in gross psychomotor acquisition, but had severe
      impaired communicative and adaptive skills. Two small regions of overlap were
      defined. The first one, located on the 3q27.3 locus and common to all patients,
      was associated with psychotic troubles and mood disorders as well as recognisable
      facial dysmorphism. This region comprised several candidate genes including SST,
      considered a candidate for the neuropsychiatric findings because of its
      implication in interneuronal migration and differentiation processes. A familial
      case with a smaller deletion allowed us to define a second region of overlap at
      the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common
      morphological findings in the first four patients included skeletal features from
      the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness
      (average Body Mass Index of 15 (18.5<N<25)) (4/4), arachnodactyly (3/4) and
      pectus excavatum (2/4)). This phenotype could be explained by the deletion of the
      AHSG gene, which encodes a secreted protein implicated in bone maturation and the
      TGFb signalling pathway. CONCLUSIONS: We report on a new microdeletional syndrome
      that associates with a recognisable facial dysmorphism and marfanoid habitus
      including scoliosis, neuropsychiatric disorders of the psychotic spectrum and
      moderate to severe ID.

PMID- 24133204
TI  - MicroRNA-27 (miR-27) targets prohibitin and impairs adipocyte differentiation and
      mitochondrial function in human adipose-derived stem cells.
AB  - Prohibitin (PHB) has been reported to play a crucial role in adipocyte
      differentiation and mitochondrial function. However, the regulative mechanism of
      PHB during adipogenesis remains unclear. In this study, we determined that the
      levels of both microRNA (miR)-27a and miR-27b were down-regulated following
      adipogenic induction of human adipose-derived stem cells, whereas the mRNA level
      of PHB was up-regulated. Overexpression of miR-27a or miR-27b inhibited PHB
      expression and adipocyte differentiation. Using PHB 3'-UTR luciferase reporter
      assay, we observed that miR-27a and miR-27b directly targeted PHB in human
      adipose-derived stem cells. A compensation of PHB partially restored the
      adipogenesis inhibited by miR-27. Moreover, we demonstrated the novel finding
      that ectopic expression of miR-27a or miR-27b impaired mitochondrial biogenesis,
      structure integrity, and complex I activity accompanied by excessive reactive
      oxygen species production. Our data suggest that miR-27 is an anti-adipogenic
      microRNA partly by targeting PHB and impairing mitochondrial function.
      Pharmacological modulation of miR-27 function may provide a new therapeutic
      strategy for the treatment of obesity. 

PMID- 24133205
TI  - Cell division cycle 7 mediates transforming growth factor-beta-induced smooth
      muscle maturation through activation of myocardin gene transcription.
AB  - Smooth muscle (SM) development consists of several processes, including cell fate
      determination, differentiation, and maturation. The molecular mechanisms
      controlling SM early differentiation have been studied extensively. However,
      little is known about the mechanism underlying SM maturation. Cell division cycle
      7 (Cdc7) has been shown to regulate cell fate determination in the initial phase
      of transforming growth factor-beta (TGF-beta)-induced SM differentiation. Our
      present study indicates that Cdc7 also regulates SM maturation. Knockdown of Cdc7
      suppresses TGF-beta-induced expression of SM myosin heavy chain, a late marker of
      SM differentiation. Cdc7 overexpression, on the other hand, enhances SM myosin
      heavy chain expression. Interestingly, Cdc7 activates the mRNA expression and
      promoter activity of myocardin (Myocd), a master regulator of SM differentiation,
      whose transcription is blocked in the initial phase of the differentiation
      because TGF-beta does not induce Myocd mRNA until after the early SM markers are
      induced. These data suggest that Cdc7 mediates TGF-beta-induced SM maturation via
      activation of Myocd transcription. Mechanistically, Cdc7 physically and
      functionally interacts with Nkx2.5 to regulate Myocd promoter activity. Cdc7
      appears to enhance Nkx2.5 binding to Myocd promoter, leading to Myocd activation.
      Taken together, our studies demonstrate that Cdc7 regulates the initial and late
      phase of SM differentiation through distinct mechanisms. 

PMID- 24133206
TI  - Distinct roles of the phosphatidate phosphatases lipin 1 and 2 during
      adipogenesis and lipid droplet biogenesis in 3T3-L1 cells.
AB  - Lipins are evolutionarily conserved Mg(2+)-dependent phosphatidate phosphatase
      (PAP) enzymes with essential roles in lipid biosynthesis. Mammals express three
      paralogues: lipins 1, 2, and 3. Loss of lipin 1 in mice inhibits adipogenesis at
      an early stage of differentiation and results in a lipodystrophic phenotype. The
      role of lipins at later stages of adipogenesis, when cells initiate the formation
      of lipid droplets, is less well characterized. We found that depletion of lipin
      1, after the initiation of differentiation in 3T3-L1 cells but before the loading
      of lipid droplets with triacylglycerol, results in a reciprocal increase of lipin
      2, but not lipin 3. We generated 3T3-L1 cells where total lipin protein and PAP
      activity levels are down-regulated by the combined depletion of lipins 1 and 2 at
      day 4 of differentiation. These cells still accumulated triacylglycerol but
      displayed a striking fragmentation of lipid droplets without significantly
      affecting their total volume per cell. This was due to the lack of the PAP
      activity of lipin 1 in adipocytes after day 4 of differentiation, whereas
      depletion of lipin 2 led to an increase of lipid droplet volume per cell. We
      propose that in addition to their roles during early adipogenesis, lipins also
      have a role in lipid droplet biogenesis. 

PMID- 24133207
TI  - Novel structural and functional insights into M3 muscarinic receptor
      dimer/oligomer formation.
AB  - Class A G protein-coupled receptors (GPCRs) are able to form homodimers and/or
      oligomeric arrays. We recently proposed, based on bioluminescence resonance
      energy transfer studies with the M3 muscarinic receptor (M3R), a prototypic class
      A GPCR, that the M3R is able to form multiple, structurally distinct dimers that
      are probably transient in nature (McMillin, S. M., Heusel, M., Liu, T., Costanzi,
      S., and Wess, J. (2011) J. Biol. Chem. 286, 28584-28598). To provide more direct
      experimental support for this concept, we employed a disulfide cross-linking
      strategy to trap various M3R dimeric species present in a native lipid
      environment (transfected COS-7 cells). Disulfide cross-linking studies were
      carried out with many mutant M3Rs containing single cysteine (Cys) substitutions
      within two distinct cytoplasmic M3R regions, the C-terminal portion of the second
      intracellular loop (i2) and helix H8 (H8). The pattern of cross-links that we
      obtained, in combination with molecular modeling studies, was consistent with the
      existence of two structurally distinct M3R dimer interfaces, one involving i2/i2
      contacts (TM4-TM5-i2 interface) and the other one characterized by H8-H8
      interactions (TM1-TM2-H8 interface). Specific H8-H8 disulfide cross-links led to
      significant impairments in M3R-mediated G protein activation, suggesting that
      changes in the structural orientation or mobility of H8 are critical for
      efficient receptor-G protein coupling. Our findings provide novel structural and
      functional insights into the mechanisms involved in M3R dimerization
      (oligomerization). Because the M3R shows a high degree of sequence similarity
      with many other class A GPCRs, our findings should be of considerable general
      interest. 

PMID- 24133208
TI  - Ca2+-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      receptors and dopamine D1 receptors regulate GluA1 trafficking in striatal
      neurons.
AB  - Regulation of striatal medium spiny neuron synapses underlies forms of motivated
      behavior and pathological drug seeking. A primary mechanism for increasing
      synaptic strength is the trafficking of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors (AMPARs) into the postsynapse, a process
      mediated by GluA1 AMPAR subunit phosphorylation. We have examined the role of
      converging glutamate and dopamine inputs in regulating biochemical cascades
      upstream of GluA1 phosphorylation. We focused on the role of Ca(2+)-permeable
      AMPARs (CPARs), which lack the GluA2 AMPAR subunit. Under conditions that
      prevented depolarization, stimulation of CPARs activated neuronal nitric oxide
      synthase and production of cGMP. CPAR-dependent cGMP production was sufficient to
      induce synaptic insertion of GluA1, detected by confocal microscopy, through a
      mechanism dependent on GluA1 Ser-845 phosphorylation. Dopamine D1 receptors, in
      contrast, stimulate GluA1 extra synaptic insertion. Simultaneous activation of
      dopamine D1 receptors and CPARs induced additive increases in GluA1 membrane
      insertion, but only CPAR stimulation augmented CPAR-dependent GluA1 synaptic
      insertion. This incorporation into the synapse proceeded through a sequential two
      step mechanism; that is, cGMP-dependent protein kinase II facilitated membrane
      insertion and/or retention, and protein kinase C activity was necessary for
      synaptic insertion. These data suggest a feed-forward mechanism for synaptic
      priming whereby an initial stimulus acting independently of voltage-gated
      conductance increases striatal neuron excitability, facilitating greater neuronal
      excitation by a subsequent stimulus. 

PMID- 24133209
TI  - The E295K cancer variant of human polymerase beta favors the mismatch
      conformational pathway during nucleotide selection.
AB  - DNA polymerase beta (pol beta) is responsible for gap filling synthesis during
      repair of damaged DNA as part of the base excision repair pathway. Human pol beta
      mutations were recently identified in a high percentage (~30%) of tumors.
      Characterization of specific cancer variants is particularly useful to further
      the understanding of the general mechanism of pol beta while providing context to
      disease contribution. We showed that expression of the carcinoma variant E295K
      induces cellular transformation. The poor polymerase activity exhibited by the
      variant was hypothesized to be caused by the destabilization of proper active
      site assembly by the glutamate to lysine mutation. Here, we show that this
      variant exhibits an unusual preference for binding dCTP opposite a templating
      adenine over the cognate dTTP. Biochemical studies indicate that the noncognate
      competes with the cognate nucleotide for binding to the polymerase active site
      with the noncognate incorporation a function of higher affinity and not increased
      activity. In the crystal structure of the variant bound to dA:dCTP, the fingers
      domain closes around the mismatched base pair. Nucleotide incorporation is
      hindered because key residues in the polymerase active site are not properly
      positioned for nucleotidyl transfer. In contrast to the noncognate dCTP, neither
      the cognate dTTP nor its nonhydrolyzable analog induced fingers closure, as
      isomorphous difference Fourier maps show that the cognate nucleotides are bound
      to the open state of the polymerase. Comparison with published structures
      provides insight into the structural rearrangements within pol beta that occur
      during the process of nucleotide discrimination. 

PMID- 24133210
TI  - Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on
      osteoclasts: actions on cytoskeletal organization, survival, and resorption.
AB  - Phosphatidylinositol 3-kinases (PI3K) participate in numerous signaling pathways,
      and control distinct biological functions. Studies using pan-PI3K inhibitors
      suggest roles for PI3K in osteoclasts, but little is known about specific PI3K
      isoforms in these cells. Our objective was to determine effects of isoform
      selective PI3K inhibitors on osteoclasts. The following inhibitors were
      investigated (targets in parentheses): wortmannin and LY294002 (pan-p110), PIK75
      (alpha), GDC0941 (alpha, delta), TGX221 (beta), AS252424 (gamma), and IC87114
      (delta). In addition, we characterized a new potent and selective PI3Kdelta
      inhibitor, GS-9820, and explored roles of PI3K isoforms in regulating osteoclast
      function. Osteoclasts were isolated from long bones of neonatal rats and rabbits.
      Wortmannin, LY294002, GDC0941, IC87114, and GS-9820 induced a dramatic retraction
      of osteoclasts within 15-20 min to 65-75% of the initial area. In contrast, there
      was no significant retraction in response to vehicle, PIK75, TGX221, or AS252424.
      Moreover, wortmannin and GS-9820, but not PIK75 or TGX221, disrupted actin belts.
      We examined effects of PI3K inhibitors on osteoclast survival. Whereas PIK75,
      TGX221, and GS-9820 had no significant effect on basal survival, all blocked
      RANKL-stimulated survival. When studied on resorbable substrates, osteoclastic
      resorption was suppressed by wortmannin and inhibitors of PI3Kbeta and PI3Kdelta,
      but not other isoforms. These data are consistent with a critical role for
      PI3Kdelta in regulating osteoclast cytoskeleton and resorptive activity. In
      contrast, multiple PI3K isoforms contribute to the control of osteoclast
      survival. Thus, the PI3Kdelta isoform, which is predominantly expressed in cells
      of hematopoietic origin, is an attractive target for anti-resorptive
      therapeutics. 

PMID- 24133211
TI  - Ribosomes regulate the stability and action of the exoribonuclease RNase R.
AB  - Ribonucleases play an important role in RNA metabolism. Yet, they are also
      potentially destructive enzymes whose activity must be controlled. Here we
      describe a novel regulatory mechanism affecting RNase R, a 3' to 5'
      exoribonuclease able to act on essentially all RNAs including those with
      extensive secondary structure. Most RNase R is sequestered on ribosomes in
      growing cells where it is stable and participates in trans-translation. In
      contrast, the free form of the enzyme, which is deleterious to cells, is
      extremely unstable, turning over with a half-life of 2 min. RNase R binding to
      ribosomes is dependent on transfer-messenger RNA (tmRNA)-SmpB, nonstop mRNA, and
      the modified form of ribosomal protein S12. Degradation of the free form of RNase
      R also requires tmRNA-SmpB, but this process is independent of ribosomes,
      indicating two distinct roles for tmRNA-SmpB. Inhibition of RNase R binding to
      ribosomes leads to slower growth and a massive increase in RNA degradation. These
      studies indicate a previously unknown role for ribosomes in cellular homeostasis.

PMID- 24133212
TI  - A soluble fragment of the tumor antigen BCL2-associated athanogene 6 (BAG-6) is
      essential and sufficient for inhibition of NKp30 receptor-dependent cytotoxicity
      of natural killer cells.
AB  - Immunosurveillance of tumor cells depends on NKp30, a major activating receptor
      of human natural killer (NK) cells. The human BCL2-associated athanogene 6 (BAG
      6, also known as BAT3; 1126 amino acids) is a cellular ligand of NKp30. To date,
      little is known about the molecular details of this receptor ligand system.
      Within the current study, we have located the binding site of NKp30 to a sequence
      stretch of 250 amino acids in the C-terminal region of BAG-6 (BAG-6(686-936)).
      BAG-6(686-936) forms a noncovalent dimer of 57-59 kDa, which is sufficient for
      high affinity interaction with NKp30 (KD < 100 nM). As our most important
      finding, BAG-6(686-936) inhibits NKp30-dependent signaling, interferon-gamma
      release, and degranulation of NK cells in the presence of malignantly transformed
      target cells. Based on these data, we show for the first time that BAG-6(686-936)
      comprises a subdomain of BAG-6, which is sufficient for receptor docking and
      inhibition of NKp30-dependent NK cell cytotoxicity as part of a tumor immune
      escape mechanism. These molecular insights provide an access point to restore
      tumor immunosurveillance by NK cells and to increase the efficacy of cellular
      therapies.

PMID- 24133213
TI  - Analysis of Drosophila glucuronyl C5-epimerase: implications for developmental
      roles of heparan sulfate sulfation compensation and 2-O-sulfated glucuronic acid.
AB  - During the biosynthesis of heparan sulfate (HS), glucuronyl C5-epimerase (Hsepi)
      catalyzes C5-epimerization of glucuronic acid (GlcA), converting it to iduronic
      acid (IdoA). Because HS 2-O-sulfotransferase (Hs2st) shows a strong substrate
      preference for IdoA over GlcA, C5-epimerization is required for normal HS
      sulfation. However, the physiological significance of C5-epimerization remains
      elusive. To understand the role of Hsepi in development, we isolated Drosophila
      Hsepi mutants. Homozygous mutants are viable and fertile with only minor
      morphological defects, including the formation of an ectopic crossvein in the
      wing, but they have a short lifespan. We propose that two mechanisms contribute
      to the mild phenotypes of Hsepi mutants: HS sulfation compensation and possible
      developmental roles of 2-O-sulfated GlcA (GlcA2S). HS disaccharide analysis
      showed that loss of Hsepi resulted in a significant impairment of 2-O-sulfation
      and induced compensatory increases in N- and 6-O-sulfation. Simultaneous block of
      Hsepi and HS 6-O-sulfotransferase (Hs6st) activity disrupted tracheoblast
      formation, a well established FGF-dependent process. This result suggests that
      the increase in 6-O-sulfation in Hsepi mutants is critical for the rescue of FGF
      signaling. We also found that the ectopic crossvein phenotype can be induced by
      expression of a mutant form of Hs2st with a strong substrate preference for GlcA
      containing units, suggesting that this phenotype is associated with abnormal GlcA
      2-O-sulfation. Finally, we show that Hsepi formed a complex with Hs2st and Hs6st
      in S2 cells, raising the possibility that this complex formation contributes to
      the close functional relationships between these enzymes. 

PMID- 24133214
TI  - Wiskott-Aldrich syndrome protein (WASp) controls the delivery of platelet
      transforming growth factor-beta1.
AB  - Platelets are immunologically competent cells containing cytokines such as TGF
      beta1 that regulate cell-mediated immunity. However, the mechanisms underlying
      cytokine secretion from platelets are undefined. The Wiskott-Aldrich syndrome
      protein (WASp) regulates actin polymerization in nucleated hematopoietic cells
      but has other role(s) in platelets. WASp-null (WASp(-/-)) platelets stimulated
      with a PAR-4 receptor agonist had increased TGF-beta1 release compared with WT
      platelets; inhibiting WASp function with wiskostatin augmented TRAP-induced TGF
      beta1 release in human platelets. TGF-beta1 release is dissociated from alpha
      granule secretion (P-selectin up-regulation) and occurs more gradually, with ~10
      15% released after 30-60 min. Blockade of Src family kinase-mediated WASp Tyr
      291/Tyr-293 phosphorylation increased TGF-beta1 release, with no additive effect
      in WASp(-/-) platelets, signifying that phosphorylation is critical for WASp
      limited TGF-beta1 secretion. Inhibiting F-actin assembly with cytochalasin D
      enhanced secretion in WT platelets and further increased TGF-beta1 release in
      WASp(-/-) platelets, indicating that WASp and actin assembly independently
      regulate TGF-beta1 release. A permeabilized platelet model was used to test the
      role of upstream small GTPases in TGF-beta1 release. N17Cdc42, but not Rac1
      mutants, increased TGF-beta1 secretion and abrogated WASp phosphorylation. We
      conclude that WASp function restricts TGF-beta1 secretion in a Cdc42- and Src
      family kinase-dependent manner and independently of actin assembly. 

PMID- 24133215
TI  - Exosomes derived from hypoxic leukemia cells enhance tube formation in
      endothelial cells.
AB  - Hypoxia plays an important role during the evolution of cancer cells and their
      microenvironment. Emerging evidence suggests communication between cancer cells
      and their microenvironment occurs via exosomes. This study aimed to clarify
      whether hypoxia affects angiogenic function through exosomes secreted from
      leukemia cells. We used the human leukemia cell line K562 for exosome-generating
      cells and human umbilical vein endothelial cells (HUVECs) for exosome target
      cells. Exosomes derived from K562 cells cultured under normoxic (20%) or hypoxic
      (1%) conditions for 24 h were isolated and quantitated by nanoparticle tracking
      analysis. These exosomes were then cocultured with HUVECs to evaluate angiogenic
      activity. The exosomes secreted from K562 cells in hypoxic conditions
      significantly enhanced tube formation by HUVECs compared with exosomes produced
      in normoxic conditions. Using a TaqMan low-density miRNA array, we found a subset
      of miRNAs, including miR-210, were significantly increased in exosomes secreted
      from hypoxic K562 cells. We demonstrated that cancer cells and their exosomes
      have altered miRNA profiles under hypoxic conditions. Although exosomes contain
      various molecular constituents such as proteins and mRNAs, altered exosomal
      compartments under hypoxic conditions, including miR-210, affected the behavior
      of endothelial cells. Our results suggest that exosomal miRNA derived from cancer
      cells under hypoxic conditions may partly affect angiogenic activity in
      endothelial cells. 

PMID- 24133216
TI  - Identification of a dithiol-disulfide switch in collapsin response mediator
      protein 2 (CRMP2) that is toggled in a model of neuronal differentiation.
AB  - Vertebrate-specific glutaredoxin 2 (Grx2) is expressed in at least two isoforms,
      mitochondrial Grx2a and cytosolic Grx2c. We have previously shown that cytosolic
      Grx2 is essential for embryonic development of the brain. In particular, we
      identified collapsin response mediator protein 2 (CRMP2/DPYSL2), a mediator of
      the semaphorin-plexin signaling pathway, as redox-regulated target of Grx2c and
      demonstrated that this regulation is required for normal axonal outgrowth. In
      this study, we demonstrate the molecular mechanism of this regulation, a specific
      and reversible intermolecular Cys-504-Cys-504 dithiol-disulfide switch in
      homotetrameric CRMP2. This switch determines two conformations of the quaternary
      CRMP2 complex that controls axonal outgrowth and thus neuronal development. 

PMID- 24133217
TI  - The strawberry pathogenesis-related 10 (PR-10) Fra a proteins control flavonoid
      biosynthesis by binding to metabolic intermediates.
AB  - Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant
      biology but their molecular function is still unclear. They are related by
      sequence and structural homology to mammalian lipid transport and plant abscisic
      acid receptor proteins and are predicted to have cavities for ligand binding.
      Recently, three new members of the PR-10 family, the Fra a proteins, have been
      identified in strawberry, where they are required for the activity of the
      flavonoid biosynthesis pathway, which is essential for the development of color
      and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids
      with different selectivity and affinities in the low MUm range. The structural
      analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5,
      and L7 surrounding the ligand-binding cavity show significant flexibility in the
      apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings
      provide mechanistic insight on the function of Fra a proteins and suggest that PR
      10 proteins, which are widespread in plants, may play a role in the control of
      secondary metabolic pathways by binding to metabolic intermediates. 

PMID- 24133218
TI  - Pan-mammalian target of rapamycin (mTOR) inhibitor AZD8055 primes
      rhabdomyosarcoma cells for ABT-737-induced apoptosis by down-regulating Mcl-1
      protein.
AB  - The PI3K/mammalian Target of Rapamycin (mTOR) pathway is often aberrantly
      activated in rhabdomyosarcoma (RMS) and represents a promising therapeutic
      target. Recent evaluation of AZD8055, an ATP-competitive mTOR inhibitor, by the
      Preclinical Pediatric Testing Program showed in vivo antitumor activity against
      childhood solid tumors, including RMS. Therefore, in the present study, we
      searched for AZD8055-based combination therapies. Here, we identify a new
      synergistic lethality of AZD8055 together with ABT-737, a BH3 mimetic that
      antagonizes Bcl-2, Bcl-xL, and Bcl-w but not Mcl-1. AZD8055 and ABT-737 cooperate
      to induce apoptosis in alveolar and embryonal RMS cells in a highly synergistic
      fashion (combination index < 0.2). Synergistic induction of apoptosis by AZD8055
      and ABT-737 is confirmed on the molecular level, as AZD8055 and ABT-737 cooperate
      to trigger loss of mitochondrial membrane potential, activation of caspases, and
      caspase-dependent apoptosis that is blocked by the pan-caspase inhibitor Z-VAD
      fmk. Similar to AZD8055, the PI3K/mTOR inhibitor NVP-BEZ235, the PI3K inhibitor
      NVP-BKM120 and Akt inhibitor synergize with ABT-737 to trigger apoptosis, whereas
      no cooperativity is found for the mTOR complex 1 inhibitor RAD001. Interestingly,
      molecular studies reveal a correlation between the ability of different PI3K/mTOR
      inhibitors to potentiate ABT-737-induced apoptosis and to suppress Mcl-1 protein
      levels. Importantly, knockdown of Mcl-1 increases ABT-737-induced apoptosis
      similar to AZD8055/ABT-737 cotreatment. This indicates that AZD8055-mediated
      suppression of Mcl-1 protein plays an important role in the synergistic drug
      interaction. By identifying a novel synergistic interaction of AZD8055 and ABT
      737, our findings have important implications for the development of molecular
      targeted therapies for RMS. 

PMID- 24133219
TI  - Respiration-related discharge of hyoglossus muscle motor units in the rat.
AB  - Although respiratory muscle motor units have been studied during natural
      breathing, simultaneous measures of muscle force have never been obtained. Tongue
      retractor muscles, such as the hyoglossus (HG), play an important role in
      swallowing, licking, chewing, breathing, and, in humans, speech. The HG is
      phasically recruited during the inspiratory phase of the respiratory cycle.
      Moreover, in urethane anesthetized rats the drive to the HG waxes and wanes
      spontaneously, providing a unique opportunity to study motor unit firing patterns
      as the muscle is driven naturally by the central pattern generator for breathing.
      We recorded tongue retraction force, the whole HG muscle EMG and the activity of
      38 HG motor units in spontaneously breathing anesthetized rats under low-force
      and high-force conditions. Activity in all cases was confined to the inspiratory
      phase of the respiratory cycle. Changes in the EMG were correlated significantly
      with corresponding changes in force, with the change in EMG able to predict 53
      68% of the force variation. Mean and peak motor unit firing rates were greater
      under high-force conditions, although the magnitude of discharge rate modulation
      varied widely across the population. Changes in mean and peak firing rates were
      significantly correlated with the corresponding changes in force, but the
      correlations were weak (r(2) = 0.27 and 0.25, respectively). These data indicate
      that, during spontaneous breathing, recruitment of HG motor units plays a
      critical role in the control of muscle force, with firing rate modulation playing
      an important but lesser role. 

PMID- 24133220
TI  - Movement speed is biased by prior experience.
AB  - How does the motor system choose the speed for any given movement? Many current
      models assume a process that finds the optimal balance between the costs of
      moving fast and the rewards of achieving the goal. Here, we show that such models
      also need to take into account a prior representation of preferred movement
      speed, which can be changed by prolonged practice. In a time-constrained reaching
      task, human participants made 25-cm reaching movements within 300, 500, 700, or
      900 ms. They were then trained for 3 days to execute the movement at either the
      slowest (900-ms) or fastest (300-ms) speed. When retested on the 4th day,
      movements executed under all four time constraints were biased toward the speed
      of the trained movement. In addition, trial-to-trial variation in speed of the
      trained movement was significantly reduced. These findings are indicative of a
      use-dependent mechanism that biases the selection of speed. Reduced speed
      variability was also associated with reduced errors in movement amplitude for the
      fast training group, which generalized nearly fully to a new movement direction.
      In contrast, changes in perpendicular error were specific to the trained
      direction. In sum, our results suggest the existence of a relatively stable but
      modifiable prior of preferred movement speed that influences the choice of
      movement speed under a range of task constraints. 

PMID- 24133221
TI  - Long-term in vivo time-lapse imaging of synapse development and plasticity in the
      cerebellum.
AB  - Synapses are continuously formed and eliminated throughout life in the mammalian
      brain, and emerging evidence suggests that this structural plasticity underlies
      experience-dependent changes of brain functions such as learning and long-term
      memory formation. However, it is generally difficult to understand how the
      rewiring of synaptic circuitry observed in vivo eventually relates to changes in
      animal's behavior. This is because afferent/efferent connections and local
      synaptic circuitries are very complicated in most brain regions, hence it is
      largely unclear how sensorimotor information is conveyed, integrated, and
      processed through a brain region that is imaged. The cerebellar cortex provides a
      particularly useful model to challenge this problem because of its simple and
      well-defined synaptic circuitry. However, owing to the technical difficulty of
      chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar
      neurons dynamically change their structures over a long period of time. Here, we
      showed that the commonly used method for neocortical in vivo imaging was not
      ideal for long-term imaging of cerebellar neurons, but simple optimization of the
      procedure significantly improved the success rate and the maximum time window of
      chronic imaging. The optimized method can be used in both neonatal and adult mice
      and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ~80% of
      animals. This method allows vital observation of dynamic cellular processes such
      as developmental refinement of synaptic circuitry as well as long-term changes of
      neuronal structures in adult cerebellum under longitudinal behavioral
      manipulations. 

PMID- 24133222
TI  - Older adults learn less, but still reduce metabolic cost, during motor
      adaptation.
AB  - The ability to learn new movements and dynamics is important for maintaining
      independence with advancing age. Age-related sensorimotor changes and increased
      muscle coactivation likely alter the trial-and-error-based process of adapting to
      new movement demands (motor adaptation). Here, we asked, to what extent is motor
      adaptation to novel dynamics maintained in older adults (>=65 yr)? We
      hypothesized that older adults would adapt to the novel dynamics less well than
      young adults. Because older adults often use muscle coactivation, we expected
      older adults to use greater muscle coactivation during motor adaptation than
      young adults. Nevertheless, we predicted that older adults would reduce muscle
      activity and metabolic cost with motor adaptation, similar to young adults.
      Seated older (n = 11, 73.8 +/- 5.6 yr) and young (n = 15, 23.8 +/- 4.7 yr) adults
      made targeted reaching movements while grasping a robotic arm. We measured their
      metabolic rate continuously via expired gas analysis. A force field was used to
      add novel dynamics. Older adults had greater movement deviations and compensated
      for just 65% of the novel dynamics compared with 84% in young adults. As
      expected, older adults used greater muscle coactivation than young adults. Last,
      older adults reduced muscle activity with motor adaptation and had consistent
      reductions in metabolic cost later during motor adaptation, similar to young
      adults. These results suggest that despite increased muscle coactivation, older
      adults can adapt to the novel dynamics, albeit less accurately. These results
      also suggest that reductions in metabolic cost may be a fundamental feature of
      motor adaptation. 

PMID- 24133223
TI  - Energy-related optimal control accounts for gravitational load: comparing
      shoulder, elbow, and wrist rotations.
AB  - We permanently deal with gravity force. Experimental evidences revealed that
      moving against gravity strongly differs from moving along the gravity vector.
      This directional asymmetry has been attributed to an optimal planning process
      that optimizes gravity force effects to minimize energy. Yet, only few studies
      have considered the case of vertical movements in the context of optimal control.
      What kind of cost is better suited to explain kinematic patterns in the vertical
      plane? Here, we aimed to understand further how the central nervous system (CNS)
      plans and controls vertical arm movements. Our reasoning was the following: if
      the CNS optimizes gravity mechanical effects on the moving limbs, kinematic
      patterns should change according to the direction and the magnitude of the
      gravity torque being encountered in the motion. Ten subjects carried out single
      joint movements, i.e., rotation around the shoulder (whole arm), elbow (forearm),
      and wrist (hand) joints, in the vertical plane. Joint kinematics were analyzed
      and compared with various theoretical optimal model predictions (minimum absolute
      work-jerk, jerk, torque change, and variance). We found both direction-dependent
      and joint-dependent variations in several kinematic parameters. Notably,
      directional asymmetries decreased according to a proximodistal gradient.
      Numerical simulations revealed that our experimental findings could be attributed
      to an optimal motor planning (minimum absolute work-jerk) that integrates the
      direction and the magnitude of gravity torque and minimizes the absolute work of
      forces (energy-related cost) around each joint. Present results support the
      general idea that the CNS implements optimal solutions according to the dynamic
      context of the action. 

PMID- 24133224
TI  - Neural correlates of motion processing through echolocation, source hearing, and
      vision in blind echolocation experts and sighted echolocation novices.
AB  - We have shown in previous research (Thaler L, Arnott SR, Goodale MA. PLoS One 6:
      e20162, 2011) that motion processing through echolocation activates temporal
      occipital cortex in blind echolocation experts. Here we investigated how neural
      substrates of echo-motion are related to neural substrates of auditory source
      motion and visual-motion. Three blind echolocation experts and twelve sighted
      echolocation novices underwent functional MRI scanning while they listened to
      binaural recordings of moving or stationary echolocation or auditory source
      sounds located either in left or right space. Sighted participants' brain
      activity was also measured while they viewed moving or stationary visual stimuli.
      For each of the three modalities separately (echo, source, vision), we then
      identified motion-sensitive areas in temporal-occipital cortex and in the planum
      temporale. We then used a region of interest (ROI) analysis to investigate cross
      modal responses, as well as laterality effects. In both sighted novices and blind
      experts, we found that temporal-occipital source-motion ROIs did not respond to
      echo-motion, and echo-motion ROIs did not respond to source-motion. This double
      dissociation was absent in planum temporale ROIs. Furthermore, temporal-occipital
      echo-motion ROIs in blind, but not sighted, participants showed evidence for
      contralateral motion preference. Temporal-occipital source-motion ROIs did not
      show evidence for contralateral preference in either blind or sighted
      participants. Our data suggest a functional segregation of processing of auditory
      source-motion and echo-motion in human temporal-occipital cortex. Furthermore,
      the data suggest that the echo-motion response in blind experts may represent a
      reorganization rather than exaggeration of response observed in sighted novices.
      There is the possibility that this reorganization involves the recruitment of
      "visual" cortical areas. 

PMID- 24133225
TI  - Reflex responses of human masseter motor units to mechanical stimulation of the
      teeth.
AB  - Our aim was to investigate the jaw reflexes using both the probability- and the
      discharge rate-based analysis methods. Twelve consenting volunteer subjects
      participated in this study. Subjects bit gently on bite bars that carried the
      impression of their teeth. Surface and intramuscular electrical activity of the
      masseter was recorded. With the help of audio feedback from one motor unit, each
      subject bit to discharge the unit at a fixed rate. While the subject continuously
      activated the selected motor unit, 4-N stimuli were delivered to the upper right
      central incisor either at a rapid or a slow rate. For each trial, >=300 stimuli
      were delivered, and, once a trial was completed, local anesthetic block was
      applied around the stimulated tooth, and the experiment was repeated. While
      preceding local anesthesia, the rapid-rate stimuli ("tap") induced substantial
      inhibitory reflex responses; during local anesthetic block, the same stimulus
      induced excitatory and inhibitory reflex responses. Slow-rate stimuli ("push"),
      on the other hand, usually generated a combination of inhibitory and excitatory
      responses that disappeared completely during the local anesthetic block. This
      study discovered that the strength of the inhibitory reflex response to a tooth
      tap stimulus was much larger than previously reported. This study also found that
      whereas the probability-based analyses were better for illustrating the existence
      and latency of small earlier responses, the discharge rate-based method was
      better for indicating the duration of earlier responses and the existence, sign,
      and duration of later responses. 

PMID- 24133228
TI  - Topographical representations of taste response characteristics in the rostral
      nucleus of the solitary tract in the rat.
AB  - The rostral nucleus of the solitary tract (rNST) is the first-order taste relay
      in rats. This study constructed topographical distributions of taste response
      characteristics (best-stimulus, response magnitude, and taste-tuning) from spike
      discharges of single neurons in the rNST. The rNST is divided into four
      subregions along the rostrocaudal (RC) axis, which include r1-r4. We explored
      single-neuron activity in r1-r3, using multibarreled glass microelectrodes. NaCl
      (N)-best neurons were localized to the rostral half of r1-r3, while HCl (H)-best
      and sucrose (S)-best neurons showed a tendency toward more caudal locations. NaCl
      and HCl (NH)-best neurons were distributed across r2-r3. The mean RC values and
      Mahalanobis distance indicated a significant difference between the distributions
      of N-best and NH-best neurons in which N-best neurons were located more
      rostrally. The region of large responses to NaCl (net response >5 spikes/s)
      overlapped with the distribution of N-best neurons. The region of large responses
      to HCl extended widely over r1-r3. The region of large responses to sucrose was
      in the medial part of r2. The excitatory region (>1 spike/s) for quinine
      overlapped with that for HCl. Neurons with sharp to moderate tuning were located
      primarily in r1-r2, while those with broad tuning were located in r2-r3. The
      robust responses to NaCl in r1-r2 primarily contributed to sharp to moderate
      taste-tuning. Neurons in r3 tended to have broad tuning, apparently due to small
      responses to both NaCl and HCl. Therefore, the rNST is spatially organized by
      neurons with distinct taste response characteristics, suggesting that these
      neurons serve different functional roles. 

PMID- 24133227
TI  - Distinguishing hair cell from neural potentials recorded at the round window.
AB  - Almost all patients who receive cochlear implants have some acoustic hearing
      prior to surgery. Electrocochleography (ECoG), or electrophysiological measures
      of cochlear response to sound, can identify remaining auditory nerve activity
      that is the basis for this residual hearing and can record potentials from hair
      cells that are no longer functionally connected to nerve fibers. The ECoG signal
      is therefore complex, being composed of both hair cell and neural signals. To
      identify signatures of different sources in the recorded potentials, we collected
      ECoG data across frequency and intensity from the round window of gerbils before
      and after treatment with kainic acid, a neurotoxin. Distortions in the recorded
      waveforms were produced by different sources over different ranges of frequency
      and intensity. In response to tones at low frequencies and low-to-moderate
      intensities, the major source of distortion was from neural phase-locking that
      was sensitive to kainic acid. At high intensities at all frequencies, the
      distortion was not sensitive to kainic acid and was consistent with asymmetric
      saturation of the hair cell transducer current. In addition to loss of phase
      locking, changes in the envelope after kainic acid treatment indicate that
      sustained neural firing combines with receptor potentials from hair cells to
      produce the envelope of the response to tones. These results provide baseline
      data to interpret comparable recordings from human cochlear implant recipients. 

PMID- 24133235
TI  - CME Quiz: New Developments in the Management of Periocular Capillary Hemangioma
      in Children.

PMID- 24133226
TI  - Characterization of age-related changes in synaptic transmission onto F344 rat
      basal forebrain cholinergic neurons using a reduced synaptic preparation.
AB  - Basal forebrain (BF) cholinergic neurons participate in a number of cognitive
      processes that become impaired during aging. We previously found that age-related
      enhancement of Ca(2+) buffering in rat cholinergic BF neurons was associated with
      impaired performance in the water maze spatial learning task (Murchison D,
      McDermott AN, Lasarge CL, Peebles KA, Bizon JL, and Griffith WH. J Neurophysiol
      102: 2194-2207, 2009). One way that altered Ca(2+) buffering could contribute to
      cognitive impairment involves synaptic function. In this report we show that
      synaptic transmission in the BF is altered with age and cognitive status. We have
      examined the properties of spontaneous postsynaptic currents (sPSCs) in
      cholinergic BF neurons that have been mechanically dissociated without enzymes
      from behaviorally characterized F344 rats. These isolated neurons retain
      functional presynaptic terminals on their somata and proximal dendrites. Using
      whole cell patch-clamp recording, we show that sPSCs and miniature PSCs are
      predominately GABAergic (bicuculline sensitive) and in all ways closely resemble
      PSCs recorded in a BF in vitro slice preparation. Adult (4-7 mo) and aged (22-24
      mo) male rats were cognitively assessed using the water maze. Neuronal phenotype
      was identified post hoc using single-cell RT-PCR. The frequency of sPSCs was
      reduced during aging, and this was most pronounced in cognitively impaired
      subjects. This is the same population that demonstrated increased intracellular
      Ca(2+) buffering. We also show that increasing Ca(2+) buffering in the synaptic
      terminals of young BF neurons can mimic the reduced frequency of sPSCs observed
      in aged BF neurons. 

PMID- 24133247
TI  - Seizure initiation and propagation in the pilocarpine rat model of temporal lobe
      epilepsy.

PMID- 24133248
TI  - alpha2delta-1 gene deletion affects somatosensory neuron function and delays
      mechanical hypersensitivity in response to peripheral nerve damage.
AB  - The alpha2delta-1 subunit of voltage-gated calcium channels is upregulated after
      sensory nerve injury and is also the therapeutic target of gabapentinoid drugs.
      It is therefore likely to play a key role in the development of neuropathic pain.
      In this study, we have examined mice in which alpha2delta-1 gene expression is
      disrupted, to determine whether alpha2delta-1 is involved in various modalities
      of nociception, and for the development of behavioral hypersensitivity after
      partial sciatic nerve ligation (PSNL). We find that naive alpha2delta-1(-/-) mice
      show a marked behavioral deficit in mechanical and cold sensitivity, but no
      change in thermal nociception threshold. The lower mechanical sensitivity is
      mirrored by a reduced in vivo electrophysiological response of dorsal horn wide
      dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord
      synaptosomes from alpha2delta-1(-/-) mice, and alpha2delta-1(-/-) DRG neurons
      exhibit lower calcium channel current density. Furthermore, a significantly
      smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL,
      alpha2delta-1(-/-) mice show delayed mechanical hypersensitivity, which only
      develops at 11 d after surgery, whereas in wild-type littermates it is maximal at
      the earliest time point measured (3 d). There is no compensatory upregulation of
      alpha2delta-2 or alpha2delta-3 after PSNL in alpha2delta-1(-/-) mice, and other
      transcripts, including neuropeptide Y and activating transcription factor-3, are
      upregulated normally. Furthermore, the ability of pregabalin to alleviate
      mechanical hypersensitivity is lost in PSNL alpha2delta-1(-/-) mice. Thus,
      alpha2delta-1 is essential for rapid development of mechanical hypersensitivity
      in a nerve injury model of neuropathic pain. 

PMID- 24133249
TI  - Structural basis of cerebellar microcircuits in the rat.
AB  - The topography of the cerebellar cortex is described by at least three different
      maps, with the basic units of each map termed "microzones," "patches," and
      "bands." These are defined, respectively, by different patterns of climbing fiber
      input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on
      embryological development, the "one-map" hypothesis proposes that the basic units
      of each map align in the adult animal and the aim of the present study was to
      test this possibility. In barbiturate anesthetized adult rats, nanoinjections of
      bidirectional tracer (Retrobeads and biotinylated dextran amine) were made into
      somatotopically identified regions within the hindlimb C1 zone in copula
      pyramidis. Injection sites were mapped relative to PC bands defined by the
      molecular marker zebrin II and were correlated with the pattern of retrograde
      cell labeling within the inferior olive and in the basilar pontine nuclei to
      determine connectivity of microzones and patches, respectively, and also with the
      distributions of biotinylated dextran amine-labeled PC terminals in the
      cerebellar nuclei. Zebrin bands were found to be related to both climbing fiber
      and mossy fiber inputs and also to cortical representation of different parts of
      the ipsilateral hindpaw, indicating a precise spatial organization within
      cerebellar microcircuitry. This precise connectivity extends to PC terminal
      fields in the cerebellar nuclei and olivonuclear projections. These findings
      strongly support the one-map hypothesis and suggest that, at the microcircuit
      level of resolution, the cerebellar cortex has a common plan of spatial
      organization for major inputs, outputs, and PC phenotype. 

PMID- 24133250
TI  - Frontal and parietal cortical interactions with distributed visual
      representations during selective attention and action selection.
AB  - Using multivoxel pattern analysis (MVPA), we studied how distributed visual
      representations in human occipitotemporal cortex are modulated by attention and
      link their modulation to concurrent activity in frontal and parietal cortex. We
      detected similar occipitotemporal patterns during a simple visuoperceptual task
      and an attention-to-working-memory task in which one or two stimuli were cued
      before being presented among other pictures. Pattern strength varied from highest
      to lowest when the stimulus was the exclusive focus of attention, a conjoint
      focus, and when it was potentially distracting. Although qualitatively similar
      effects were seen inside regions relatively specialized for the stimulus category
      and outside, the former were quantitatively stronger. By regressing
      occipitotemporal pattern strength against activity elsewhere in the brain, we
      identified frontal and parietal areas exerting top-down control over, or reading
      information out from, distributed patterns in occipitotemporal cortex. Their
      interactions with patterns inside regions relatively specialized for that
      stimulus category were higher than those with patterns outside those regions and
      varied in strength as a function of the attentional condition. One area, the
      frontal operculum, was distinguished by selectively interacting with
      occipitotemporal patterns only when they were the focus of attention. There was
      no evidence that any frontal or parietal area actively inhibited occipitotemporal
      representations even when they should be ignored and were suppressed. Using MVPA
      to decode information within these frontal and parietal areas showed that they
      contained information about attentional context and/or readout information from
      occipitotemporal cortex to guide behavior but that frontal regions lacked
      information about category identity. 

PMID- 24133251
TI  - Doc2b synchronizes secretion from chromaffin cells by stimulating fast and
      inhibiting sustained release.
AB  - Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE
      dependent exocytosis in mouse chromaffin cells, but the role of a closely related
      calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in
      chromaffin cells using Doc2b knock-out mice and high temporal resolution
      measurements of exocytosis. We found that the calcium dependence of vesicle
      priming and release triggering remained unchanged, ruling out an obligatory role
      for Doc2b in those processes. However, in the absence of Doc2b, release was
      shifted from the readily releasable pool to the subsequent sustained component.
      Conversely, upon overexpression of Doc2b, the sustained component was largely
      inhibited whereas the readily releasable pool was augmented. Electron microscopy
      revealed an increase in the total number of vesicles upon Doc2b overexpression,
      ruling out vesicle depletion as the cause for the reduced sustained component.
      Further experiments showed that, in the absence of Doc2b, the refilling of the
      readily releasable vesicle pools is faster, but incomplete. Faster refilling
      leads to an increase in the sustained component as newly primed vesicles fuse
      while the [Ca(2+)]i following stimulation is still high. We conclude that Doc2b
      acts to inhibit vesicle priming during prolonged calcium elevations, thus
      protecting unprimed vesicles from fusing prematurely, and redirecting them to
      refill the readily releasable pool after relaxation of the calcium signal. In
      sum, Doc2b favors fast, synchronized release, and limits out-of-phase secretion. 

PMID- 24133252
TI  - Synaptic regulation of microtubule dynamics in dendritic spines by calcium, F
      actin, and drebrin.
AB  - Dendritic spines are actin-rich compartments that protrude from the microtubule
      rich dendritic shafts of principal neurons. Spines contain receptors and
      postsynaptic machinery for receiving the majority of glutamatergic inputs. Recent
      studies have shown that microtubules polymerize from dendritic shafts into spines
      and that signaling through synaptic NMDA receptors regulates this process.
      However, the mechanisms regulating microtubule dynamics in dendrites and spines
      remain unclear. Here we show that in hippocampal neurons from male and female
      mice, the majority of microtubules enter spines from highly localized sites at
      the base of spines. These entries occur in response to synapse-specific calcium
      transients that promote microtubule entry into active spines. We further document
      that spine calcium transients promote local actin polymerization, and that F
      actin is both necessary and sufficient for microtubule entry. Finally, we show
      that drebrin, a protein known to mediate interactions between F-actin and
      microtubules, acts as a positive regulator of microtubule entry into spines.
      Together these results establish for the first time the essential mechanisms
      regulating microtubule entry into spines and contribute importantly to our
      understanding of the role of microtubules in synaptic function and plasticity. 

PMID- 24133253
TI  - Integration of direction cues is invariant to the temporal gap between them.
AB  - Many decisions involve integration of evidence conferred by discrete cues over
      time. However, the neural mechanism of this integration is poorly understood.
      Several decision-making models suggest that integration of evidence is
      implemented by a dynamic system whose state evolves toward a stable point
      representing the decision outcome. The internal dynamics of such point attractor
      models render them sensitive to the temporal gaps between cues because their
      internal forces push the state forward once it is dislodged from the initial
      stable point. We asked whether human subjects are as sensitive to such temporal
      gaps. Subjects reported the net direction of stochastic random dot motion, which
      was presented in one or two brief observation windows (pulses). Pulse strength
      and interpulse interval varied randomly from trial to trial. We found that
      subjects' performance was largely invariant to the interpulse intervals up to at
      least 1 s. The findings question the implementation of the integration process
      via mechanisms that rely on autonomous changes of network state. The mechanism
      should be capable of freezing the state of the network at a variety of firing
      rate levels during temporal gaps between the cues, compatible with a line of
      stable attractor states. 

PMID- 24133255
TI  - The hand sees visual periphery better than the eye: motor-dependent visual motion
      analyses.
AB  - Information pertaining to visual motion is used in the brain not only for
      conscious perception but also for various kinds of motor controls. In contrast to
      the increasing amount of evidence supporting the dissociation of visual
      processing for action versus perception, it is less clear whether the analysis of
      visual input is shared for characterizing various motor outputs, which require
      different kinds of interactions with environments. Here we show that, in human
      visuomotor control, motion analysis for quick hand control is distinct from that
      for quick eye control in terms of spatiotemporal analysis and spatial
      integration. The amplitudes of implicit and quick hand and eye responses induced
      by visual motion stimuli differently varied with stimulus size and pattern
      smoothness (e.g., spatial frequency). Surprisingly, the hand response did not
      decrease even when the visual motion with a coarse pattern was mostly occluded
      over the visual center, whereas the eye response markedly decreased. Since these
      contrasts cannot be ascribed to any difference in motor dynamics, they clearly
      indicate different spatial integration of visual motion for the individual motor
      systems. Going against the overly unified hierarchical view of visual analysis,
      our data suggest that visual motion analyses are separately tailored from early
      levels to individual motor modalities. Namely, the hand and eyes see the external
      world differently. 

PMID- 24133254
TI  - Opposing action of nuclear factor kappaB and Polo-like kinases determines a
      homeostatic end point for excitatory synaptic adaptation.
AB  - Homeostatic responses critically adjust synaptic strengths to maintain stability
      in neuronal networks. Compensatory adaptations to prolonged excitation include
      induction of Polo-like kinases (Plks) and degradation of spine-associated Rap
      GTPase-activating protein (SPAR) to reduce synaptic excitation, but mechanisms
      that limit overshooting and allow refinement of homeostatic adjustments remain
      poorly understood. We report that Plks produce canonical pathway-mediated
      activation of the nuclear factor kappaB (NF-kappaB) transcription factor in a
      process that requires the kinase activity of Plks. Chronic elevated activity,
      which induces Plk expression, also produces Plk-dependent activation of NF
      kappaB. Deficiency of NF-kappaB, in the context of exogenous Plk2 expression or
      chronic elevated neuronal excitation, produces exaggerated homeostatic reductions
      in the size and density of dendritic spines, synaptic AMPA glutamate receptor
      levels, and excitatory synaptic currents. During the homeostatic response to
      chronic elevated activity, NF-kappaB activation by Plks subsequently opposes Plk
      mediated SPAR degradation by transcriptionally upregulating SPAR in mouse
      hippocampal neurons in vitro and in vivo. Exogenous SPAR expression can rescue
      the overshooting of homeostatic reductions at excitatory synapses in NF-kappaB
      deficient neurons responding to elevated activity. Our data establish an integral
      feedback loop involving NF-kappaB, Plks, and SPAR that regulates the end point of
      homeostatic synaptic adaptation to elevated activity and are the first to
      implicate a transcription factor in the regulation of homeostatic synaptic
      responses. 

PMID- 24133257
TI  - Modeling fall propensity in Parkinson's disease: deficits in the attentional
      control of complex movements in rats with cortical-cholinergic and striatal
      dopaminergic deafferentation.
AB  - Cognitive symptoms, complex movement deficits, and increased propensity for falls
      are interrelated and levodopa-unresponsive symptoms in patients with Parkinson's
      disease (PD). We developed a test system for the assessment of fall propensity in
      rats and tested the hypothesis that interactions between loss of cortical
      cholinergic and striatal dopaminergic afferents increase fall propensity. Rats
      were trained to traverse stationary and rotating rods, placed horizontally or at
      inclines, and while exposed to distractors. Rats also performed an operant
      Sustained Attention Task (SAT). Partial cortical cholinergic and/or caudate
      dopaminergic deafferentation were produced by bilateral infusions of 192 IgG
      saporin (SAP) into the basal forebrain and/or 6-hydroxydopamine (6-OHDA) into the
      caudate nucleus, respectively, modeling the lesions seen in early PD. Rats with
      dual cholinergic-dopaminergic lesions (DL) fell more frequently than SAP or 6
      OHDA rats. Falls in DL rats were associated with incomplete rebalancing after
      slips and low traversal speed. Ladder rung walking and pasta handling performance
      did not indicate sensorimotor deficits. SAT performance was impaired in DL and
      SAP rats; however, SAT performance and falls were correlated only in DL rats.
      Furthermore, in DL rats, but not in rats with only dopaminergic lesions, the
      placement and size of dopaminergic lesion correlated significantly with fall
      rates. The results support the hypothesis that after dual cholinergic
      dopaminergic lesions, attentional resources can no longer be recruited to
      compensate for diminished striatal control of complex movement, thereby
      "unmasking" impaired striatal control of complex movements and yielding falls. 

PMID- 24133256
TI  - miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social
      context of singing behavior in zebra finches.
AB  - Mutations in the FOXP2 gene cause speech and language impairments, accompanied by
      structural and functional abnormalities in brain regions underlying speech
      related sensory-motor processing, including the striatum and cerebellum. The
      sequence and expression patterns of FOXP2 are highly conserved among higher
      vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal
      nucleus required for vocal learning, and reduced FoxP2 expression impairs
      dendritic development and vocal learning. The FoxP2 gene encodes a transcription
      factor that controls the expression of many downstream genes. However, how FOXP2
      gene expression is regulated is not clearly understood. miRNAs regulate gene
      expression post-transcriptionally by targeting the 3'-untranslated regions (UTRs)
      of mRNAs, leading to translational suppression or mRNA degradation. In this
      study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2
      gene. We show that both miR-9 and miR-140-5p target specific sequences in the
      FoxP2 3'-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also
      show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch
      brain is regulated during song development in juvenile zebra finches. We further
      show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X
      is regulated as a function of the social context of song behavior in males
      singing undirected songs. Our findings reveal a post-transcriptional mechanism
      that regulates FoxP2 expression and suggest that social vocal behavior can
      influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2
      gene regulatory network. 

PMID- 24133258
TI  - alpha2-Chimaerin regulates a key axon guidance transition during development of
      the oculomotor projection.
AB  - The ocular motor system consists of three nerves which innervate six muscles to
      control eye movements. In humans, defective development of this system leads to
      eye movement disorders, such as Duane Retraction Syndrome, which can result from
      mutations in the alpha2-chimaerin signaling molecule. We have used the zebrafish
      to model the role of alpha2-chimaerin during development of the ocular motor
      system. We first mapped ocular motor spatiotemporal development, which occurs
      between 24 and 72 h postfertilization (hpf), with the oculomotor nerve following
      an invariant sequence of growth and branching to its muscle targets. We
      identified 52 hpf as a key axon guidance "transition," when oculomotor axons
      reach the orbit and select their muscle targets. Live imaging and quantitation
      showed that, at 52 hpf, axons undergo a switch in behavior, with striking changes
      in the dynamics of filopodia. We tested the role of alpha2-chimaerin in this
      guidance process and found that axons expressing gain-of-function alpha2
      chimaerin isoforms failed to undergo the 52 hpf transition in filopodial
      dynamics, leading to axon stalling. alpha2-chimaerin loss of function led to
      ecotopic and misguided branching and hypoplasia of oculomotor axons; embryos had
      defective eye movements as measured by the optokinetic reflex. Manipulation of
      chimaerin signaling in oculomotor neurons in vitro led to changes in microtubule
      stability. These findings demonstrate that a correct level of alpha2-chimaerin
      signaling is required for key oculomotor axon guidance decisions, and provide a
      zebrafish model for Duane Retraction Syndrome. 

PMID- 24133259
TI  - The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid
      beta oligomer toxicity.
AB  - In Alzheimer's disease (AD), soluble amyloid-beta oligomers (AbetaOs) trigger
      neurotoxic signaling, at least partially, via the cellular prion protein
      (PrP(C)). However, it is unknown whether other ligands of PrP(C) can regulate
      this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an
      Hsp90 cochaperone secreted by astrocytes, binds to PrP(C) in the vicinity of the
      AbetaO binding site to protect neurons against toxic stimuli. Here, we
      investigated a potential role of STI1 in AbetaO toxicity. We confirmed the
      specific binding of AbetaOs and STI1 to the PrP and showed that STI1 efficiently
      inhibited AbetaO binding to PrP in vitro (IC50 of ~70 nm) and also decreased
      AbetaO binding to cultured mouse primary hippocampal neurons. Treatment with STI1
      prevented AbetaO-induced synaptic loss and neuronal death in mouse cultured
      neurons and long-term potentiation inhibition in mouse hippocampal slices.
      Interestingly, STI1-haploinsufficient neurons were more sensitive to AbetaO
      induced cell death and could be rescued by treatment with recombinant STI1.
      Noteworthy, both AbetaO binding to PrP(C) and PrP(C)-dependent AbetaO toxicity
      were inhibited by TPR2A, the PrP(C)-interacting domain of STI1. Additionally,
      PrP(C)-STI1 engagement activated alpha7 nicotinic acetylcholine receptors, which
      participated in neuroprotection against AbetaO-induced toxicity. We found an age
      dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD
      and in the brains of AD-affected individuals, suggesting a compensatory response.
      Our findings reveal a previously unrecognized role of the PrP(C) ligand STI1 in
      protecting neurons in AD and suggest a novel pathway that may help to offset
      AbetaO-induced toxicity. 

PMID- 24133261
TI  - Synapsin function in GABA-ergic interneurons is required for short-term olfactory
      habituation.
AB  - In Drosophila, short-term (STH) and long-term habituation (LTH) of olfactory
      avoidance behavior are believed to arise from the selective potentiation of
      GABAergic synapses between multiglomerular local circuit interneurons (LNs) and
      projection neurons in the antennal lobe. However, the underlying mechanisms
      remain poorly understood. Here, we show that synapsin (syn) function is necessary
      for STH and that syn(97)-null mutant defects in STH can be rescued by syn(+) cDNA
      expression solely in the LN1 subset of GABAergic local interneurons. As synapsin
      is a synaptic vesicle-clustering phosphoprotein, these observations identify a
      presynaptic mechanism for STH as well as the inhibitory interneurons in which
      this mechanism is deployed. Serine residues 6 and/or 533, potential kinase target
      sites of synapsin, are necessary for synapsin function suggesting that synapsin
      phosphorylation is essential for STH. Consistently, biochemical analyses using a
      phospho-synapsin-specific antiserum show that synapsin is a target of Ca(2+)
      calmodulin-dependent kinase II (CaMKII) phosphorylation in vivo. Additional
      behavioral and genetic observations demonstrate that CaMKII function is necessary
      in LNs for STH. Together, these data support a model in which CaMKII-mediated
      synapsin phosphorylation in LNs induces synaptic vesicle mobilization and thereby
      presynaptic facilitation of GABA release that underlies olfactory STH. Finally,
      the striking observation that LTH occurs normally in syn(97) mutants indicates
      that signaling pathways for STH and LTH diverge upstream of synapsin function in
      GABAergic interneurons. 

PMID- 24133260
TI  - The neuromuscular transform of the lobster cardiac system explains the opposing
      effects of a neuromodulator on muscle output.
AB  - Motor neuron activity is transformed into muscle movement through a cascade of
      complex molecular and biomechanical events. This nonlinear mapping of neural
      inputs to motor behaviors is called the neuromuscular transform (NMT). We
      examined the NMT in the cardiac system of the lobster Homarus americanus by
      stimulating a cardiac motor nerve with rhythmic bursts of action potentials and
      measuring muscle movements in response to different stimulation patterns. The NMT
      was similar across preparations, which suggested that it could be used to predict
      muscle movement from spontaneous neural activity in the intact heart. We assessed
      this possibility across semi-intact heart preparations in two separate analyses.
      First, we performed a linear regression analysis across 122 preparations in
      physiological saline to predict muscle movements from neural activity. Under
      these conditions, the NMT was predictive of contraction duty cycle but was unable
      to predict contraction amplitude, likely as a result of uncontrolled interanimal
      variability. Second, we assessed the ability of the NMT to predict changes in
      motor output induced by the neuropeptide C-type allatostatin. Wiwatpanit et al.
      (2012) showed that bath application of C-type allatostatin produced either
      increases or decreases in the amplitude of the lobster heart contractions. We
      show that an important component of these preparation-dependent effects can arise
      from quantifiable differences in the basal state of each preparation and the
      nonlinear form of the NMT. These results illustrate how properly characterizing
      the relationships between neural activity and measurable physiological outputs
      can provide insight into seemingly idiosyncratic effects of neuromodulators
      across individuals. 

PMID- 24133262
TI  - Multistate structural modeling and voltage-clamp analysis of epilepsy/autism
      mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the
      channel closed state.
AB  - Voltage-gated potassium channel Kv10.2 (KCNH5) is expressed in the nervous
      system, but its functions and involvement in human disease are poorly understood.
      We studied a human Kv10.2 channel mutation (R327H) recently identified in a child
      with epileptic encephalopathy and autistic features. Using multistate structural
      modeling, we demonstrate that the Arg327 residue in the S4 helix of voltage
      sensing domain has strong ionic interactions with negatively charged residues
      within the S1-S3 helices in the resting (closed) and early-activation state but
      not in the late-activation and fully-activated (open) state. The R327H mutation
      weakens ionic interactions between residue 327 and these negatively charged
      residues, thus favoring channel opening. Voltage-clamp analysis showed a strong
      hyperpolarizing (~70 mV) shift of voltage dependence of activation and an
      acceleration of activation. Our results demonstrate the critical role of the
      Arg327 residue in stabilizing the channel closed state and explicate for the
      first time the structural and functional change of a Kv10.2 channel mutation
      associated with neurological disease. 

PMID- 24133263
TI  - Visual response properties of V1 neurons projecting to V2 in macaque.
AB  - Visual area V2 of the primate cortex receives the largest projection from area
      V1. V2 is thought to use its striate inputs as the basis for computations that
      are important for visual form processing, such as signaling angles, object
      borders, illusory contours, and relative binocular disparity. However, it remains
      unclear how selectivity for these stimulus properties emerges in V2, in part
      because the functional properties of the inputs are unknown. We used antidromic
      electrical stimulation to identify V1 neurons that project directly to V2 (10% of
      all V1 neurons recorded) and characterized their electrical and visual responses.
      V2-projecting neurons were concentrated in the superficial and middle layers of
      striate cortex, consistent with the known anatomy of this cortico-cortical
      circuit. Most were fast conducting and temporally precise in their electrical
      responses, and had broad spike waveforms consistent with pyramidal regular
      spiking excitatory neurons. Overall, projection neurons were functionally
      diverse. Most, however, were tuned for orientation and binocular disparity and
      were strongly suppressed by large stimuli. Projection neurons included those
      selective and invariant to spatial phase, with roughly equal proportions.
      Projection neurons found in superficial layers had longer conduction times,
      broader spike waveforms, and were more responsive to chromatic stimuli; those
      found in middle layers were more strongly selective for motion direction and
      binocular disparity. Collectively, these response properties may be well suited
      for generating complex feature selectivity in and beyond V2. 

PMID- 24133264
TI  - A hierarchy of attentional priority signals in human frontoparietal cortex.
AB  - Humans can voluntarily attend to a variety of visual attributes to serve
      behavioral goals. Voluntary attention is believed to be controlled by a network
      of dorsal frontoparietal areas. However, it is unknown how neural signals
      representing behavioral relevance (attentional priority) for different attributes
      are organized in this network. Computational studies have suggested that a
      hierarchical organization reflecting the similarity structure of the task demands
      provides an efficient and flexible neural representation. Here we examined the
      structure of attentional priority using functional magnetic resonance imaging.
      Participants were cued to attend to location, color, or motion direction within
      the same stimulus. We found a hierarchical structure emerging in frontoparietal
      areas, such that multivoxel patterns for attending to spatial locations were most
      distinct from those for attending to features, and the latter were further
      clustered into different dimensions (color vs motion). These results provide
      novel evidence for the organization of the attentional control signals at the
      level of distributed neural activity. The hierarchical organization provides a
      computationally efficient scheme to support flexible top-down control. 

PMID- 24133265
TI  - Long-lasting spinal oxytocin analgesia is ensured by the stimulation of
      allopregnanolone synthesis which potentiates GABA(A) receptor-mediated synaptic
      inhibition.
AB  - Hypothalamospinal control of spinal pain processing by oxytocin (OT) has received
      a lot of attention in recent years because of its potency to reduce pain symptoms
      in inflammatory and neuropathic conditions. However, cellular and molecular
      mechanisms underlying OT spinal antinociception are still poorly understood. In
      this study, we used biochemical, electrophysiological, and behavioral approaches
      to demonstrate that OT levels are elevated in the spinal cord of rats exhibiting
      pain symptoms, 24 h after the induction of inflammation with an intraplantar
      injection of lambda-carrageenan. Using a selective OT receptor antagonist, we
      demonstrate that this elevated OT content is responsible for a tonic analgesia
      exerted on both mechanical and thermal modalities. This phenomenon appeared to be
      mediated by an OT receptor-mediated stimulation of neurosteroidogenesis, which
      leads to an increase in GABA(A) receptor-mediated synaptic inhibition in lamina
      II spinal cord neurons. We also provide evidence that this novel mechanism of OT
      mediated spinal antinociception may be controlled by extracellular signal-related
      protein kinases, ERK1/2, after OT receptor activation. The oxytocinergic
      inhibitory control of spinal pain processing is emerging as an interesting target
      for future therapies since it recruits several molecular mechanisms, which are
      likely to exert a long-lasting analgesia through nongenomic and possibly genomic
      effects.

PMID- 24133266
TI  - Amplified cold transduction in native nociceptors by M-channel inhibition.
AB  - Topically applied camphor elicits a sensation of cool, but nothing is known about
      how it affects cold temperature sensing. We found that camphor sensitizes a
      subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to
      cold, but desensitizes and partially blocks heterologously expressed TRPM8
      (transient receptor potential cation channel subfamily M member 8). In contrast,
      camphor reduces potassium outward currents in cultured sensory neurons and, in
      cold nociceptors, the cold-sensitizing effects of camphor and menthol are
      additive. Using a membrane potential dye-based screening assay and heterologously
      expressed potassium channels, we found that the effects of camphor are mediated
      by inhibition of Kv7.2/3 channels subtypes that generate the M-current in
      neurons. In line with this finding, the specific M-current blocker XE991
      reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M
      channel blocking effects of XE991 and camphor are not sufficient to initiate cold
      transduction but require a cold-activated inward current generated by TRPM8. The
      cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold
      nociceptors. Low-threshold corneal cold thermoreceptors that express high levels
      of TRPM8 and lack potassium channels are not affected by camphor. We also found
      that menthol--like camphor--potently inhibits Kv7.2/3 channels. The apparent
      functional synergism arising from TRPM8 activation and M-current block can
      improve the effectiveness of topical coolants and cooling lotions, and may also
      enhance TRPM8-mediated analgesia.

PMID- 24133267
TI  - Object representation in inferior temporal cortex is organized hierarchically in
      a mosaic-like structure.
AB  - There are two dominant models for the functional organization of brain regions
      underlying object recognition. One model postulates category-specific modules
      while the other proposes a distributed representation of objects with generic
      visual features. Functional imaging techniques relying on metabolic signals, such
      as fMRI and optical intrinsic signal imaging (OISI), have been used to support
      both models, but due to the indirect nature of the measurements in these
      techniques, the existing data for one model cannot be used to support the other
      model. Here, we used large-scale multielectrode recordings over a large surface
      of anterior inferior temporal (IT) cortex, and densely mapped stimulus-evoked
      neuronal responses. We found that IT cortex is subdivided into distinct domains
      characterized by similar patterns of responses to the objects in our stimulus
      set. Each domain spanned several millimeters on the cortex. Some of these domains
      represented faces ("face" domains) or monkey bodies ("monkey-body" domains). We
      also identified domains with low responsiveness to faces ("anti-face" domains).
      Meanwhile, the recording sites within domains that displayed category selectivity
      showed heterogeneous tuning profiles to different exemplars within each category.
      This local heterogeneity was consistent with the stimulus-evoked feature columns
      revealed by OISI. Taken together, our study revealed that regions with common
      functional properties (domains) consist of a finer functional structure (columns)
      in anterior IT cortex. The "domains" and previously proposed "patches" are rather
      like "mosaics" where a whole mosaic is characterized by overall similarity in
      stimulus responses and pieces of the mosaic correspond to feature columns. 

PMID- 24133268
TI  - Medial and lateral networks in anterior prefrontal cortex support metacognitive
      ability for memory and perception.
AB  - Convergent evidence indicates that frontopolar Brodmann area 10, and more
      generally the anterior prefrontal cortex (aPFC), supports the human capacity to
      monitor and reflect on cognition and experience. An important unanswered
      question, however, is whether aPFC is a homogeneous region that supports a
      general-purpose metacognitive ability or whether there could be regional
      specialization within aPFC with respect to specific types of metacognitive
      processes. Previous studies suggest that the lateral and medial subdivisions
      within aPFC may support metacognitive judgments of moment-to-moment perceptual
      processes and assessments of information from memory stored over longer time
      scales, respectively. Here we directly compared intraindividual variability in
      metacognitive capacity for perceptual decisions and memorial judgments and used
      resting-state functional connectivity (rs-fcMRI) to relate this variability to
      the connectivity of the medial and lateral regions of aPFC. We found a behavioral
      dissociation in metacognitive ability for perceptual and memorial judgments.
      Furthermore, functional connectivity analysis revealed distinct patterns of
      connectivity that correlated with individual differences in each domain.
      Metacognitive ability for perceptual decisions was associated with greater
      connectivity between lateral regions of aPFC and right dorsal anterior cingulate
      cortex, bilateral putamen, right caudate, and thalamus, whereas metacognitive
      ability for memory retrieval predicted greater connectivity between medial aPFC
      and the right central precuneus and intraparietal sulcus/inferior parietal
      lobule. Together, these results suggest that an individual's capacity for
      accurate introspection in the domains of perception and memory is related to the
      functional integrity of unique neural networks anchored in the medial and lateral
      regions of the aPFC. 

PMID- 24133269
TI  - Shared vulnerability of two synaptically-connected medial temporal lobe areas to
      age and cognitive decline: a seven tesla magnetic resonance imaging study.
AB  - The medial temporal lobe (MTL) is the first brain area to succumb to
      neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human
      tissue evaluation suggests that this pathology propagates in an ordered manner,
      with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum
      lacunosum-moleculare (CA1-SRLM)--two monosynaptically connected structures-
      exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM
      share an early vulnerability to AD pathology, then atrophy should occur in a
      proportional manner between the two structures. We tested this hypothesis in
      living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL
      microstructure. Among a pool of age-matched healthy controls and patients with
      amnestic mild cognitive impairment and mild AD, we found a significant
      correlation between ERC and CA1-SRLM size that could not be explained by global
      atrophy affecting the MTL. Of the various structures that contribute axons or
      dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor
      of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically
      connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC
      structural covariance was significant for older controls and not patients,
      whereas the opposite pattern emerged for a correlation between CA1-SRLM and
      episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL
      structures to atrophy in older controls relative to a younger comparison group.
      Together, these findings suggest that ERC and CA1-SRLM share vulnerability to
      both age and AD-associated atrophy.

PMID- 24133270
TI  - Gap junction-dependent homolog avoidance in the developing CNS.
AB  - Oppositely directed projections of some homologous neurons in the developing CNS
      of the medicinal leech (Hirudo verbana), such as the AP cells, undergo a form of
      contact-dependent homolog avoidance. Embryonic APs extend axons within the
      connective nerve toward adjacent ganglia, in which they meet and form gap
      junctions (GJs) with the oppositely directed axons of their segmental homologs,
      stop growing, and are later permanently retracted (Wolszon et al., 1994a,b).
      However, early deletion of an AP neuron leads to resumed growth and permanent
      maintenance of the projections of neighboring APs. Here we test the hypothesis
      that a GJ-based signaling mechanism is responsible for this instance of homolog
      avoidance. We demonstrate that selective knockdown of GJ gene Hve-inx1 expression
      in single embryonic APs, by expressing a short-hairpin interfering RNA, leads to
      continued growth of the projections of the cell toward, into, and beyond adjacent
      ganglia. Moreover, the projections of the APs in adjacent ganglia also resume
      growth, mimicking their responses to cell deletion. Continued growth was also
      observed when two different INX1 mutant transgenes that abolish dye coupling
      between APs were expressed. These include a mutant transgene that effectively
      downregulates all GJ plaques that include the INX1 protein and a closed channel
      INX1 mutant that retains the adhesive cellular binding characteristic of INX1 GJs
      but not the open channel pore function. Our results add GJ intercellular
      communication to the list of molecular signaling mechanisms that can act as
      mediators of growth-inhibiting cell-cell interactions that define the topography
      of neuronal arbors. 

PMID- 24133271
TI  - Saccade modulation by optical and electrical stimulation in the macaque frontal
      eye field.
AB  - Recent studies have demonstrated that strong neural modulations can be evoked
      with optogenetic stimulation in macaque motor cortex without observing any evoked
      movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why
      such perturbations do not generate movements and if conditions exist under which
      they may evoke movements. In this study, we examine the effects of five
      optogenetic constructs in the macaque frontal eye field and use electrical
      microstimulation to assess whether optical perturbation of the local network
      leads to observable motor changes during optical, electrical, and combined
      stimulation. We report a significant increase in the probability of evoking
      saccadic eye movements when low current electrical stimulation is coupled to
      optical stimulation compared with when electrical stimulation is used alone.
      Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with
      simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with
      optical stimulation but strong activity with electrical stimulation. Our findings
      suggest that stimulation with current ChR2 optogenetic constructs generates
      subthreshold activity that contributes to the initiation of movements but, in
      most cases, is not sufficient to evoke a motor response. 

PMID- 24133272
TI  - Titration of Syntaxin1 in mammalian synapses reveals multiple roles in vesicle
      docking, priming, and release probability.
AB  - Synaptic vesicles undergo sequential steps in preparation for neurotransmitter
      release. Individual SNARE proteins and the SNARE complex itself have been
      implicated in these processes. However, discrete effects of SNARE proteins on
      synaptic function have been difficult to assess using complete loss-of-function
      approaches. We therefore used a genetic titration technique in cultured mouse
      hippocampal neurons to evaluate the contribution of the neuronal SNARE protein
      Syntaxin1 (Stx1) in vesicle docking, priming, and release probability. We
      generated graded reductions of total Stx1 levels by combining two approaches,
      namely, endogenous hypomorphic expression of the isoform Stx1B and RNAi-mediated
      knockdown. Proximity of synaptic vesicles to the active zone was not strongly
      affected. However, overall release efficiency of affected neurons was severely
      impaired, as demonstrated by a smaller readily releasable pool size, slower
      refilling rate of primed vesicles, and lower release probability. Interestingly,
      dose-response fitting of Stx1 levels against readily releasable pool size and
      vesicular release probability showed similar Kd (dissociation constant) values at
      18% and 19% of wild-type Stx1, with cooperativity estimates of 3.4 and 2.5,
      respectively. This strongly suggests that priming and vesicle fusion share the
      same molecular stoichiometry, and are governed by highly related mechanisms. 

PMID- 24133273
TI  - Diverse suppressive influences in area MT and selectivity to complex motion
      features.
AB  - Neuronal selectivity results from both excitatory and suppressive inputs to a
      given neuron. Suppressive influences can often significantly modulate neuronal
      responses and impart novel selectivity in the context of behaviorally relevant
      stimuli. In this work, we use a naturalistic optic flow stimulus to explore the
      responses of neurons in the middle temporal area (MT) of the alert macaque
      monkey; these responses are interpreted using a hierarchical model that
      incorporates relevant nonlinear properties of upstream processing in the primary
      visual cortex (V1). In this stimulus context, MT neuron responses can be
      predicted from distinct excitatory and suppressive components. Excitation is
      spatially localized and matches the measured preferred direction of each neuron.
      Suppression is typically composed of two distinct components: (1) a directionally
      untuned component, which appears to play the role of surround suppression and
      normalization; and (2) a direction-selective component, with comparable tuning
      width as excitation and a distinct spatial footprint that is usually partially
      overlapping with excitation. The direction preference of this direction-tuned
      suppression varies widely across MT neurons: approximately one-third have
      overlapping suppression in the opposite direction as excitation, and many other
      neurons have suppression with similar direction preferences to excitation. There
      is also a population of MT neurons with orthogonally oriented suppression. We
      demonstrate that direction-selective suppression can impart selectivity of MT
      neurons to more complex velocity fields and that it can be used for improved
      estimation of the three-dimensional velocity of moving objects. Thus, considering
      MT neurons in a complex stimulus context reveals a diverse set of computations
      likely relevant for visual processing in natural visual contexts. 

PMID- 24133274
TI  - Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating
      kinetics and are inhibited by mGluR1 activation.
AB  - We investigated the subthreshold properties of an erg (ether-a-go-go-related
      gene) K(+) current in Purkinje cells of neonatal mice. Action potentials recorded
      from Purkinje cells in cerebellar slices exhibited a decreased threshold
      potential and increased frequency of spontaneous and repetitive activity
      following application of the specific erg channel blocker E-4031. Accommodation
      was absent before and after drug application. The erg current of these Purkinje
      cells activated at membrane potentials near -60 mV and exhibited fast gating
      kinetics. The functional importance of fast gating subthreshold erg channels in
      Purkinje cells was corroborated by comparing the results of action potential
      clamp experiments with erg1a, erg1b, erg2, and erg3 currents heterologously
      expressed in HEK cells. Computer simulations based on a NEURON model of Purkinje
      cells only reproduced the effects of the native erg current when an erg channel
      conductance like that of erg3 was included. Experiments with subunit-sensitive
      toxins (BeKm-1, APETx1) indicated that erg channels in Purkinje cells are
      presumably mediated by heteromeric erg1/erg3 or modified erg1 channels. Following
      mGluR1 activation, the native erg current was reduced by ~70%, brought about by
      reduction of the maximal erg current and a shift of the activation curve to more
      positive potentials. The Purkinje cell erg current contributed to the sustained
      current component of the biphasic mGluR1 response. Activation of mGluR1 by the
      agonist 3,4-dihydroxyphenylglycol increased Purkinje cell excitability, similar
      to that induced by E-4031. The results indicated that erg currents can be
      modulated and may contribute to the mGluR1-induced plasticity changes in Purkinje
      cells. 

PMID- 24133275
TI  - Musical training enhances neural processing of binaural sounds.
AB  - While hearing in noise is a complex task, even in high levels of noise humans
      demonstrate remarkable hearing ability. Binaural hearing, which involves the
      integration and analysis of incoming sounds from both ears, is an important
      mechanism that promotes hearing in complex listening environments. Analyzing
      inter-ear differences helps differentiate between sound sources--a key mechanism
      that facilitates hearing in noise. Even when both ears receive the same input,
      known as diotic hearing, speech intelligibility in noise is improved. Although
      musicians have better speech-in-noise perception compared with non-musicians, we
      do not know to what extent binaural processing contributes to this advantage.
      Musicians often demonstrate enhanced neural responses to sound, however, which
      may undergird their speech-in-noise perceptual enhancements. Here, we recorded
      auditory brainstem responses in young adult musicians and non-musicians to a
      speech stimulus for which there was no musician advantage when presented
      monaurally. When presented diotically, musicians demonstrated faster neural
      timing and greater intertrial response consistency relative to non-musicians.
      Furthermore, musicians' enhancements to the diotically presented stimulus
      correlated with speech-in-noise perception. These data provide evidence for
      musical training's impact on biological processes and suggest binaural processing
      as a possible contributor to more proficient hearing in noise.

PMID- 24133276
TI  - Functional subdomains within human FFA.
AB  - The fusiform face area (FFA) is a well-studied human brain region that shows
      strong activation for faces. In functional MRI studies, FFA is often assumed to
      be a homogeneous collection of voxels with similar visual tuning. To test this
      assumption, we used natural movies and a quantitative voxelwise modeling and
      decoding framework to estimate category tuning profiles for individual voxels
      within FFA. We find that the responses in most FFA voxels are strongly enhanced
      by faces, as reported in previous studies. However, we also find that responses
      of individual voxels are selectively enhanced or suppressed by a wide variety of
      other categories and that these broader tuning profiles differ across FFA voxels.
      Cluster analysis of category tuning profiles across voxels reveals three
      spatially segregated functional subdomains within FFA. These subdomains differ
      primarily in their responses for nonface categories, such as animals, vehicles,
      and communication verbs. Furthermore, this segregation does not depend on the
      statistical threshold used to define FFA from responses to functional localizers.
      These results suggest that voxels within FFA represent more diverse information
      about object and action categories than generally assumed. 

PMID- 24133277
TI  - Cell-specific fine-tuning of neuronal excitability by differential expression of
      modulator protein isoforms.
AB  - SLOB (SLOWPOKE-binding protein) modulates the Drosophila SLOWPOKE calcium
      activated potassium channel. We have shown previously that SLOB deletion or RNAi
      knockdown decreases excitability of neurosecretory pars intercerebralis (PI)
      neurons in the adult Drosophila brain. In contrast, we found that SLOB
      deletion/knockdown enhances neurotransmitter release from motor neurons at the
      fly larval neuromuscular junction, suggesting an increase in excitability.
      Because two prominent SLOB isoforms, SLOB57 and SLOB71, modulate SLOWPOKE
      channels in opposite directions in vitro, we investigated whether divergent
      expression patterns of these two isoforms might underlie the differential
      modulation of excitability in PI and motor neurons. By performing detailed in
      vitro and in vivo analysis, we found strikingly different modes of regulatory
      control by the slob57 and slob71 promoters. The slob71, but not slob57, promoter
      contains binding sites for the Hunchback and Mirror transcriptional repressors.
      Furthermore, several core promoter elements that are absent in the slob57
      promoter coordinately drive robust expression of a luciferase vector by the
      slob71 promoter in vitro. In addition, we visualized the expression patterns of
      the slob57 and slob71 promoters in vivo and found clear spatiotemporal
      differences in promoter activity. SLOB57 is expressed prominently in adult PI
      neurons, whereas larval motor neurons exclusively express SLOB71. In contrast, at
      the larval neuromuscular junction, SLOB57 expression appears to be restricted
      mainly to a subset of glial cells. Our results illustrate how the use of
      alternative transcriptional start sites within an ion channel modulator locus
      coupled with functionally relevant alternative splicing can be used to fine-tune
      neuronal excitability in a cell-specific manner. 

PMID- 24133278
TI  - Glycine transporter-1 inhibition promotes striatal axon sprouting via NMDA
      receptors in dopamine neurons.
AB  - NMDA receptor activity is involved in shaping synaptic connections throughout
      development and adulthood. We recently reported that brief activation of NMDA
      receptors on cultured ventral midbrain dopamine neurons enhanced their axon
      growth rate and induced axonal branching. To test whether this mechanism was
      relevant to axon regrowth in adult animals, we examined the reinnervation of
      dorsal striatum following nigral dopamine neuron loss induced by unilateral
      intrastriatal injections of the toxin 6-hydroxydopamine. We used a
      pharmacological approach to enhance NMDA receptor-dependent signaling by
      treatment with an inhibitor of glycine transporter-1 that elevates levels of
      extracellular glycine, a coagonist required for NMDA receptor activation. All
      mice displayed sprouting of dopaminergic axons from spared fibers in the ventral
      striatum to the denervated dorsal striatum at 7 weeks post-lesion, but the
      reinnervation in mice treated for 4 weeks with glycine uptake inhibitor was
      approximately twice as dense as in untreated mice. The treated mice also
      displayed higher levels of striatal dopamine and a complete recovery from
      lateralization in a test of sensorimotor behavior. We confirmed that the actions
      of glycine uptake inhibition on reinnervation and behavioral recovery required
      NMDA receptors in dopamine neurons using targeted deletion of the NR1 NMDA
      receptor subunit in dopamine neurons. Glycine transport inhibitors promote
      functionally relevant sprouting of surviving dopamine axons and could provide
      clinical treatment for disorders such as Parkinson's disease. 

PMID- 24133279
TI  - Optic flow stimuli update anterodorsal thalamus head direction neuronal activity
      in rats.
AB  - Head direction (HD) neurons fire selectively according to head orientation in the
      yaw plane relative to environmental landmark cues. Head movements provoke optic
      field flow signals that enter the vestibular nuclei, indicating head velocity,
      and hence angular displacements. To test whether optic field flow alone affects
      the directional firing of HD neurons, rats walked about on a circular platform as
      a spot array was projected onto the surrounding floor-to-ceiling cylindrical
      black curtain. Directional responses in the anterodorsal thalamus of four rats
      remained stable as they moved about with the point field but in the absence of
      landmark cues. Then, the spherical projector was rotated about its yaw axis at
      4.5 degrees /s for ~90 s. In 27 sessions the mean drift speed of the preferred
      directions (PDs) was 1.48 degrees /s (SD=0.78 degrees /s; range: 0.15 to 2.88
      degrees /s). Thus, optic flow stimulation entrained PDs, albeit at drift speeds
      slower than the field rotation. This could be due to conflicts with vestibular,
      motor command, and efferent copy signals. After field rotation ended, 20/27 PDs
      drifted back to within 45 degrees  of the initial values over several minutes,
      generally following the shortest path to return to the initial value.
      Poststimulation drifts could change speed and/or direction, with mean speeds of
      0.68+/-0.64 degrees /s (range 0 to 1.36 degrees /s). Since the HD cell pathway
      (containing anterodorsal thalamus) is the only known projection of head direction
      information to entorhinal grid cells and hippocampal place cells, yaw plane optic
      flow signals likely influence representations in this spatial reference
      coordinate system for orientation and navigation. 

PMID- 24133280
TI  - Large-scale brain networks in the awake, truly resting marmoset monkey.
AB  - Resting-state functional MRI is a powerful tool that is increasingly used as a
      noninvasive method for investigating whole-brain circuitry and holds great
      potential as a possible diagnostic for disease. Despite this potential, few
      resting-state studies have used animal models (of which nonhuman primates
      represent our best opportunity of understanding complex human neuropsychiatric
      disease), and no work has characterized networks in awake, truly resting animals.
      Here we present results from a small New World monkey that allows for the
      characterization of resting-state networks in the awake state. Six adult common
      marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint
      using individualized helmets. Following behavioral training, resting BOLD data
      were acquired during eight consecutive 10 min scans for each conscious subject.
      Group independent component analysis revealed 12 brain networks that overlap
      substantially with known anatomically constrained circuits seen in the awake
      human. Specifically, we found eight sensory and "lower-order" networks (four
      visual, two somatomotor, one cerebellar, and one caudate-putamen network), and
      four "higher-order" association networks (one default mode-like network, one
      orbitofrontal, one frontopolar, and one network resembling the human salience
      network). In addition to their functional relevance, these network patterns bear
      great correspondence to those previously described in awake humans. This first-of
      its-kind report in an awake New World nonhuman primate provides a platform for
      mechanistic neurobiological examination for existing disease models established
      in the marmoset. 

PMID- 24133282
TI  - Relationship between the local structure of orientation map and the strength of
      orientation tuning of neurons in monkey V1: a 2-photon calcium imaging study.
AB  - A majority of neurons in the monkey primary visual cortex (V1) are tuned to
      stimulus orientations. Preferred orientations and tuning strengths vary among V1
      neurons. The preferred orientation of neurons gradually changes across the cortex
      with occasional failures of this organization. How V1 neurons are arranged by the
      strength of orientation tuning and whether neuronal arrangement for tuning
      strength relates to orientation preference maps remains controversial. In this
      study, we performed in vivo two-photon calcium imaging in macaque V1 to examine
      the local spatial organization of orientation tuning at the level of single
      cells. We recorded fluorescence signals from individual neurons loaded with a
      calcium-sensitive dye in layer 2 and the uppermost tier of layer 3. The strength
      of orientation tuning was shared by nearby neurons, and changed across the
      cortex. The neurons with similar tuning strength were distributed across at least
      the entire thickness of layer 2. The tuning strength was weaker in regions where
      neurons exhibited heterogeneous preferred orientations, as compared with regions
      where neurons shared similar orientation preferences. Nearby direction-selective
      neurons often shared their preferred directions, although only a few neurons were
      direction selective in the layers examined. Thus, the orientation tuning strength
      of V1 neurons is partially predictable from the local structure of orientation
      map. The weaker orientation tuning we found in regions with heterogeneous
      orientation preferences suggests that orientation-independent interactions among
      local populations of V1 neurons play a critical role in determining their
      orientation tuning. 

PMID- 24133281
TI  - Oligodendrocyte/type-2 astrocyte progenitor cells and glial-restricted precursor
      cells generate different tumor phenotypes in response to the identical oncogenes.
AB  - Despite the great interest in identifying the cell-of-origin for different
      cancers, little knowledge exists regarding the extent to which the specific
      origin of a tumor contributes to its properties. To directly examine this
      question, we expressed identical oncogenes in two types of glial progenitor
      cells, glial-restricted precursor (GRP) cells and oligodendrocyte/type-2
      astrocyte progenitor cells (O-2A/OPCs), and in astrocytes of the mouse CNS
      (either directly purified or generated from GRP cells). In vitro, expression of
      identical oncogenes in these cells generated populations differing in expression
      of antigens thought to identify tumor initiating cells, generation of 3D
      aggregates when grown as adherent cultures, and sensitivity to the
      chemotherapeutic agent BCNU. In vivo, cells differed in their ability to form
      tumors, in malignancy and even in the type of host-derived cells infiltrating the
      tumor mass. Moreover, identical genetic modification of these different cells
      yielded benign infiltrative astrocytomas, malignant astrocytomas, or tumors with
      characteristics seen in oligodendrogliomas and small-cell astrocytomas,
      indicating a contribution of cell-of-origin to the characteristic properties
      expressed by these different tumors. Our studies also revealed unexpected
      relationships between the cell-of-origin, differentiation, and the order of
      oncogene acquisition at different developmental stages in enabling neoplastic
      growth. These studies thus provide multiple novel demonstrations of the
      importance of the cell-of-origin in respect to the properties of transformed
      cells derived from them. In addition, the approaches used enable analysis of the
      role of cell-of-origin in tumor biology in ways that are not accessible by other
      more widely used approaches. 

PMID- 24133283
TI  - The neural cell adhesion molecule promotes maturation of the presynaptic
      endocytotic machinery by switching synaptic vesicle recycling from adaptor
      protein 3 (AP-3)- to AP-2-dependent mechanisms.
AB  - Newly formed synapses undergo maturation during ontogenetic development via
      mechanisms that remain poorly understood. We show that maturation of the
      presynaptic endocytotic machinery in CNS neurons requires substitution of the
      adaptor protein 3 (AP-3) with AP-2 at the presynaptic plasma membrane. In mature
      synapses, AP-2 associates with the intracellular domain of the neural cell
      adhesion molecule (NCAM). NCAM promotes binding of AP-2 over binding of AP-3 to
      presynaptic membranes, thus favoring the substitution of AP-3 for AP-2 during
      formation of mature synapses. The presynaptic endocytotic machinery remains
      immature in adult NCAM-deficient (NCAM-/-) mice accumulating AP-3 instead of AP-2
      and its partner protein AP180 in synaptic membranes and vesicles. NCAM deficiency
      or disruption of the NCAM/AP-2 complex in wild-type (NCAM+/+) neurons by
      overexpression of AP-2 binding-defective mutant NCAM interferes with efficient
      retrieval of the synaptic vesicle v-SNARE synaptobrevin 2. Abnormalities in
      synaptic vesicle endocytosis and recycling may thus contribute to neurological
      disorders associated with mutations in NCAM. 

PMID- 24133284
TI  - Distinct parietal and temporal connectivity profiles of ventrolateral frontal
      areas involved in language production.
AB  - Broca's region, which in the language-dominant hemisphere of the human brain
      plays a major role in language production, includes two distinct
      cytoarchitectonic areas: 44 and 45. The unique connectivity patterns of these two
      areas have not been well established. In a resting-state functional connectivity
      study, we tested predictions about these areas from invasive tract-tracing
      studies of the connectivity of their homologs in the macaque monkey. We
      demonstrated their distinct connectivity profiles as well as their differences
      from the caudally adjacent ventral parts of the premotor cortex and the primary
      motor cortical region that represent the orofacial musculature. Area 45 is
      strongly connected with the superior temporal sulcus and the cortex on the
      adjacent superior and middle temporal gyri. In the parietal region, area 45 is
      connected with the angular gyrus, whereas area 44 is connected with the
      supramarginal gyrus. The primary motor cortical region in the caudal precentral
      gyrus is not connected with the posterior parietal region, which lies outside the
      confines of the postcentral gyrus, whereas the ventrorostral premotor cortical
      area 6VR, in the most anterior part of the precentral gyrus, has strong
      connections with the rostral supramarginal gyrus. Thus, area 44, which has
      stronger connections to the posterior supramarginal gyrus, can be distinguished
      from both the adjacent area 6VR and area 45. These findings provide a major
      improvement in understanding the connectivity of the areas in the ventrolateral
      frontal region that are involved in language production. 

PMID- 24133286
TI  - Cognitive deficits in mild Parkinson's disease are associated with distinct areas
      of grey matter atrophy.
AB  - BACKGROUND AND OBJECTIVES: The neuroanatomical substrates underlying cognitive
      impairment in Parkinson's disease (PD) remain poorly understood. To address this
      gap, we compared the grey matter atrophy patterns in PD patients with mild
      cognitive impairment (PD-MCI) with PD patients having no cognitive impairment (PD
      NCI), and examined relationships between atrophic regions and cognitive
      performance in specific domains. METHODS: 90 non-demented PD patients (64.95+/
      7.54 years, Hoehn and Yahr=1.88+/-0.39) were classified using formal diagnostic
      criteria as PD-MCI (n=23) or PD-NCI (n=67). Grey matter volume differences were
      examined using voxel-based morphometry on structural MRI, and multivariate linear
      regressions were employed to assess the relationships between cognitive
      performance in specific domains and atrophic regions. RESULTS: Patients with PD
      MCI had lower global cognition scores compared with PD-NCI (Mini Mental State
      Examination: 26.9 vs. 28.4, p=0.011; Montreal Cognitive Assessment: 24.5 vs.
      27.0, p<0.001). The PD-MCI group demonstrated significantly poorer performance on
      executive function, attention, memory and language abilities. Patients with PD
      MCI had reductions in grey matter volumes in the left insular, left superior
      frontal and left middle temporal areas compared to PD-NCI. Multiple regressions
      controlling for age, education and cardiovascular risk factors revealed
      significant positive correlations between left insular atrophy and executive
      attention dysfunction. CONCLUSIONS: Domain specific cognitive impairment in mild
      PD is associated with distinct areas of grey matter atrophy. These regions of
      atrophy are demonstrable early in the disease course and may serve as a biomarker
      for dementia in PD.

PMID- 24133285
TI  - Atrophy in distinct corticolimbic networks in frontotemporal dementia relates to
      social impairments measured using the Social Impairment Rating Scale.
AB  - Patients with frontotemporal dementia (FTD) often exhibit prominent, early and
      progressive impairments in social behaviour. We developed the Social Impairment
      Rating Scale (SIRS), rated by a clinician after a structured interview, which
      grades the types and severity of social behavioural symptoms in seven domains. In
      20 FTD patients, we used the SIRS to study the anatomic basis of social
      impairments. In support of hypotheses generated from a prior study of healthy
      adults, we found that the relative magnitude of brain atrophy in three partially
      dissociable corticolimbic networks anchored in the amygdala predicted the
      severity of distinct social impairments measured using the SIRS. Patients with
      the greatest atrophy in a mesolimbic, reward-related (affiliation) network
      exhibited the most severe socioemotional detachment, whereas patients with the
      greatest atrophy in an interoceptive, pain-related (aversion) network exhibited
      the most severe lack of social apprehension. Patients with the greatest atrophy
      in a perceptual network exhibited the most severe lack of awareness or
      understanding of others' social and emotional behaviour. Our findings underscore
      observations that FTD is associated with heterogeneous social symptoms that can
      be understood in a refined manner by measuring impairments in component processes
      subserved by dissociable neural networks. Furthermore, these findings support the
      validity of the SIRS as an instrument to measure the social symptoms of patients
      with FTD. Ultimately, we hope it will be useful as a longitudinal outcome measure
      in natural history studies and in clinical trials of putative interventions to
      improve social functioning.

PMID- 24133288
TI  - Don't know what they are, but treatable? Therapies for conversion disorders.

PMID- 24133287
TI  - An algorithmic approach to structural imaging in dementia.
AB  - Accurate and timely diagnosis of dementia is important to guide management and
      provide appropriate information and support to patients and families. Currently,
      with the exception of individuals with genetic mutations, postmortem examination
      of brain tissue remains the only definitive means of establishing diagnosis in
      most cases, however, structural neuroimaging, in combination with clinical
      assessment, has value in improving diagnostic accuracy during life. Beyond the
      exclusion of surgical pathology, signal change and cerebral atrophy visible on
      structural MRI can be used to identify diagnostically relevant imaging features,
      which provide support for clinical diagnosis of neurodegenerative dementias.
      While no structural imaging feature has perfect sensitivity and specificity for a
      given diagnosis, there are a number of imaging characteristics which provide
      positive predictive value and help to narrow the differential diagnosis. While
      neuroradiological expertise is invaluable in accurate scan interpretation, there
      is much that a non-radiologist can gain from a focused and structured approach to
      scan analysis. In this article we describe the characteristic MRI findings of the
      various dementias and provide a structured algorithm with the aim of providing
      clinicians with a practical guide to assessing scans. 

PMID- 24133289
TI  - Apathy correlates with prefrontal amyloid beta deposition in Alzheimer's disease.
AB  - OBJECTIVE: Neuropsychiatric symptoms affect many patients with Alzheimer's
      disease (AD). ((11)C)Pittsburgh Compound-B (PIB) positron emission tomography
      (PET) has enabled the in vivo visualisation of brain amyloid-beta (Abeta)
      deposition. This study exploratively investigated the correlation between brain
      Abeta deposition measured by ((11)C)PIB PET and neuropsychiatric symptoms in AD.
      METHODS: Participants were 28 patients (15 women, 13 men) with PIB-positive AD.
      Clinical assessments included Mini-Mental State Examination, Clinical Dementia
      Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All
      patients underwent three-dimensional T1-weighted MRI and ((11)C)PIB PET. The
      distribution volume ratio (DVR), an index of ((11)C)PIB retention and, thus,
      Abeta deposition, was estimated voxel by voxel from ((11)C)PIB PET data with
      partial volume correction. Voxel-based correlation analysis was performed to
      assess the relationships between DVR and each NPI subscale. Additionally, voxel
      based analysis of covariance (ANCOVA) of the DVR images was performed between
      Patients with AD with and without each neuropsychiatric symptom. Voxel-based
      morphometry analysis of MRI was also performed. RESULTS: Apathy subscale was
      correlated with ((11)C)PIB retention in the bilateral frontal and right anterior
      cingulate. ((11)C)PIB retention was greater in the bilateral frontal cortex of
      patients with AD with apathy than those of without apathy. Overlapping areas
      between the two analyses were the bilateral orbitofrontal gyrus and left superior
      frontal gyrus. Other NPI subscales were not correlated with ((11)C)PIB retention.
      Voxel-based morphometry analysis of MRI showed no significant cluster of
      correlation between grey matter volume and NPI subscales. CONCLUSIONS: This study
      revealed that prefrontal Abeta deposition correlates with apathy.

PMID- 24133290
TI  - Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results
      from a national surveillance cohort.
AB  - BACKGROUND: Autoantibodies to glial, myelin and neuronal antigens have been
      reported in a range of central demyelination syndromes and autoimmune
      encephalopathies in children, but there has not been a systematic evaluation
      across the range of central nervous system (CNS) autoantibodies in childhood
      acquired demyelinating syndromes (ADS). METHODS: Children under the age of 16
      years with first-episode ADS were identified from a national prospective
      surveillance study; serum from 65 patients had been sent for a variety of
      diagnostic tests. Antibodies to astrocyte, myelin and neuronal antigens were
      tested or retested in all samples. RESULTS: Fifteen patients (23%) were positive
      for at least one antibody (Ab): AQ4-Ab was detected in three; two presenting with
      neuromyelitis optica (NMO) and one with isolated optic neuritis (ON). Myelin
      oligodendrocyte glycoprotein (MOG)-Ab was detected in seven; two with acute
      disseminated encephalomyelitis (ADEM), two with ON, one with transverse myelitis
      (TM) and two with clinically isolated syndrome (CIS). N-Methyl-D-Aspartate
      receptor (NMDAR)-Ab was found in two; one presenting with ADEM and one with ON.
      Voltage-gated potassium channel (VGKC)-complex antibodies were positive in three;
      one presenting with ADEM, one with ON and one with CIS. GlyR-Ab was detected in
      one patient with TM. All patients were negative for the VGKC-complex-associated
      proteins LGI1, CASPR2 and contactin-2. CONCLUSIONS: A range of CNS-directed
      autoantibodies were found in association with childhood ADS. Although these
      antibodies are clinically relevant when associated with the specific neurological
      syndromes that have been described, further studies are required to evaluate
      their roles and clinical relevance in demyelinating diseases.

PMID- 24133291
TI  - Control of fixation duration during scene viewing by interaction of foveal and
      peripheral processing.
AB  - Processing in our visual system is functionally segregated, with the fovea
      specialized in processing fine detail (high spatial frequencies) for object
      identification, and the periphery in processing coarse information (low
      frequencies) for spatial orienting and saccade target selection. Here we
      investigate the consequences of this functional segregation for the control of
      fixation durations during scene viewing. Using gaze-contingent displays, we
      applied high-pass or low-pass filters to either the central or the peripheral
      visual field and compared eye-movement patterns with an unfiltered control
      condition. In contrast with predictions from functional segregation, fixation
      durations were unaffected when the critical information for vision was strongly
      attenuated (foveal low-pass and peripheral high-pass filtering); fixation
      durations increased, however, when useful information was left mostly intact by
      the filter (foveal high-pass and peripheral low-pass filtering). These patterns
      of results are difficult to explain under the assumption that fixation durations
      are controlled by foveal processing difficulty. As an alternative explanation, we
      developed the hypothesis that the interaction of foveal and peripheral processing
      controls fixation duration. To investigate the viability of this explanation, we
      implemented a computational model with two compartments, approximating spatial
      aspects of processing by foveal and peripheral activations that change according
      to a small set of dynamical rules. The model reproduced distributions of fixation
      durations from all experimental conditions by variation of few parameters that
      were affected by specific filtering conditions. 

PMID- 24133293
TI  - On the limited effect of stimulus boundaries on saccade metrics.
AB  - How the endpoint of saccadic eye movements is determined out of many potential
      peripheral locations is a crucial issue in the field of vision. Models of saccade
      generation account for this seemingly selective process in terms of competitive
      interactions between populations of neurons that encode respectively for
      different saccade amplitudes and directions. However, these models do not specify
      which visual stimulus properties other than the relative location of the stimuli
      are involved and how these properties contribute to ultimately determine a single
      saccade endpoint. We addressed this issue by contrasting the respective
      contributions of the 2-D spatial extent of the stimuli and the location of their
      boundaries in a global-effect paradigm. Participants were presented a to-be
      looked-at peripheral target stimulus with or without a less eccentric visually
      invariant distractor. The extent of the target stimulus was manipulated in either
      one or two dimensions, such that targets differed either by their 2-D spatial
      extent (small, medium, or large circle) or the location of their boundaries
      (circle vs. horizontal or vertical ellipse of medium size). Results showed that
      the distractor deviated the eyes away from the target with the deviation varying
      with the 2-D spatial extent of the target but not the location of its boundaries.
      This finding suggests that the spatial distribution of luminance contrast and/or
      the number of elementary features that compose the stimuli prevails over visual
      boundaries in specifying the saccade endpoint. Implications for models of saccade
      generation are discussed. 

PMID- 24133292
TI  - Attention modulates generalization of visuomotor adaptation.
AB  - Generalization represents the ability to transfer what has been learned in one
      context to another context beyond limited experience. Because acquired motor
      representations often have to be reinstated in a different or novel environment,
      generalization is a crucial part of visuomotor learning. In daily life, training
      for new motor skills often occurs in a complex environment, in which dividing
      attentional resources for multiple stimuli is required. However, it is unknown
      how dividing attention during learning affects the generalization of visuomotor
      learning. We examined how divided attention during training modulates the
      generalization of visuomotor rotational adaptation. Participants were trained to
      adapt to one direction with or without dividing attention to a simultaneously
      presented visual detection task. Then, they had to generalize rotational
      adaptation to other untrained directions. We show that visuomotor training with
      divided attention multiplicatively reduces the gain and sharpens the tuning of
      the generalization function. We suggest that limiting attention narrowly
      restricts an internal model, reducing the range and magnitude of transfer. This
      result suggests that attention modulates a selective subpopulation of neurons in
      motor areas, those with directional tuning values in or near the training
      direction. 

PMID- 24133294
TI  - Allocentric visual cues influence mental transformation of bodies.
AB  - Identifying a human body stimulus involves mentally rotating an embodied spatial
      representation of one's body (motoric embodiment) and projecting it onto the
      stimulus (spatial embodiment). Interactions between these two processes (spatial
      and motoric embodiment) may thus reveal cues about the underlying reference
      frames. The allocentric visual reference frame, and hence the perceived
      orientation of the body relative to gravity, was modulated using the York
      Tumbling Room, a fully furnished cubic room with strong directional cues that can
      be rotated around a participant's roll axis. Sixteen participants were seated
      upright (relative to gravity) in the Tumbling Room and made judgments about body
      and hand stimuli that were presented in the frontal plane at orientations of 0
      degrees , 90 degrees , 180 degrees  (upside down), or 270 degrees  relative to
      them. Body stimuli have an intrinsic visual polarity relative to the environment
      whereas hands do not. Simultaneously the room was oriented 0 degrees , 90 degrees
      , 180 degrees  (upside down), or 270 degrees  relative to gravity resulting in
      sixteen combinations of orientations. Body stimuli were more accurately
      identified when room and body stimuli were aligned. However, such congruency did
      not facilitate identifying hand stimuli. We conclude that static allocentric
      visual cues can affect embodiment and hence performance in an egocentric mental
      transformation task. Reaction times to identify either hands or bodies showed no
      dependence on room orientation. 

PMID- 24133295
TI  - What do fast response times tell us about attentional control?
AB  - The mental experience of attention capture has attracted a great deal of intrigue
      among researchers seeking to explain the interactions between stimulus-driven and
      goal-driven attentional control. In recent years, researchers have increasingly
      begun to analyze cumulative response time (RT) distributions to test modern
      accounts of the capture phenomenon, particularly accounts claiming that there are
      changes in susceptibility to distraction as a function of time. In this paper, we
      raise a criticism of this approach, which centers on a problematic assumption.
      The assumption is that variability in these distributions is primarily determined
      by fluctuations in the observer's internal control state (e.g., readiness for the
      trial). However, it is also the case that faster segments of the distributions
      are overrepresented by trials that are objectively easy, while slower segments
      are overrepresented by trials that are objectively difficult. That is, incidental
      aspects of the trial stimuli influence task performance independently of the
      observer's internal control state. Here, we demonstrate empirically that
      contributions of incidental stimulus factors distort cumulative RT distributions
      in such a way that confounds proper interpretation of experimental data. The
      results have implications for theoretical accounts of attentional control, and
      they also raise caution about the assumptions that are sometimes made when
      analyzing cumulative RT distributions. 

PMID- 24133296
TI  - Embedding multilevel survival analysis of dyadic social interaction in structural
      equation models: hazard rates as both outcomes and predictors.
AB  - OBJECTIVE: Demonstrate multivariate multilevel survival analysis within a larger
      structural equation model. Test the 3 hypotheses that when confronted by a
      negative parent, child rates of angry, sad/fearful, and positive emotion will
      increase, decrease, and stay the same, respectively, for antisocial compared with
      normal children. This same pattern will predict increases in future antisocial
      behavior. METHODS: Parent-child dyads were videotaped in the fall of kindergarten
      in the laboratory and antisocial behavior ratings were obtained in the fall of
      kindergarten and third grade. RESULTS: Kindergarten antisocial predicted less
      child sad/fear and child positive but did not predict child anger given parent
      negative. Less child positive and more child neutral given parent negative
      predicted increases in third-grade antisocial behavior. CONCLUSIONS: The model is
      a useful analytic tool for studying rates of social behavior. Lack of positive
      affect or excess neutral affect may be a new risk factor for child antisocial
      behavior.

PMID- 24133297
TI  - Pharmacokinetic and pharmacodynamic properties of GS-9620, a novel Toll-like
      receptor 7 agonist, demonstrate interferon-stimulated gene induction without
      detectable serum interferon at low oral doses.
AB  - GS-9620 [8-(3-(pyrrolidin-1-ylmethyl)benzyl)-4-amino-2-butoxy-7,8-dihydropteridin
      6(5H)-one] is a potent, orally bioavailable small-molecule agonist of Toll-like
      receptor 7 (TLR7) developed for finite treatment of chronic hepatitis B viral
      (HBV) infection, with the goal of inducing a liver-targeted antiviral effect
      without inducing the adverse effects associated with current systemic interferon
      alpha (IFN-alpha) therapies. We characterized the pharmacodynamic response of GS
      9620 in CD-1 mice and cynomolgus monkeys following intravenous or oral
      administration and showed that GS-9620 induces the production of select
      chemokines and cytokines, including IFN-alpha and interferon-stimulated genes
      (ISGs). It is noteworthy that we also demonstrated that, in animals and healthy
      human volunteers, oral administration of GS-9620 can induce a type I interferon
      dependent antiviral innate immune response, as measured by whole-blood mRNA of
      the ISGs 2'5'-oligoadenylate synthetase 1 (OAS1) and myxovirus resistance 1
      (MX1), without the induction of detectable systemic IFN-alpha, i.e., a
      presystemic response. Additionally, presystemic induction of hepatic OAS1 and MX1
      mRNA was observed in CD-1 mice in the absence of detectable systemic IFN-alpha.
      We propose that the mechanism of this presystemic response is likely its high
      intestinal absorption, which facilitates localized activation of TLR7, probably
      in plasmacytoid dendritic cells at the level of gut-associated lymphoid tissue
      and/or the liver. This localized response is further supported by data that
      indicate only minimal contributions of systemic immune stimulation to the overall
      pharmacodynamic response to orally administered GS-9620. These data demonstrate
      that GS-9620 can induce an antiviral innate immune response without inducing a
      systemic IFN-alpha response and thus suggest the therapeutic potential of this
      approach in the treatment of chronic HBV infection. 

PMID- 24133298
TI  - Seeking a valid gold standard for an innovative, dialect-neutral language test.
AB  - PURPOSE In this study, the authors explored alternative gold standards to
      validate an innovative, dialect-neutral language assessment. METHOD Participants
      were 78 African American children, ages 5;0 (years;months) to 6;11. Twenty
      participants had previously been identified as having language impairment. The
      Diagnostic Evaluation of Language Variation-Norm Referenced (DELV-NR; Seymour,
      Roeper, & J. de Villiers, 2005) was administered, and concurrent language samples
      (LSs) were collected. Using LS profiles as the gold standard, sensitivity,
      specificity, and other measures of diagnostic accuracy were compared for
      diagnoses made from the DELV-NR and participants' clinical status prior to
      recruitment. In a second analysis, the authors used results from the first
      analysis to make evidence-based adjustments in the estimates of DELV-NR
      diagnostic accuracy. RESULTS Accuracy of the DELV-NR relative to LS profiles was
      greater than that of prior diagnoses, indicating that the DELV-NR was an
      improvement over preexisting diagnoses for this group. Specificity met
      conventional standards, but sensitivity was somewhat low. Reanalysis using the
      positive and negative predictive power of the preexisting diagnosis in a
      discrepant-resolution procedure revealed that estimates for sensitivity and
      specificity for the DELV-NR were .85 and .93, respectively. CONCLUSION The
      authors found that, even after making allowances for the imperfection of
      available gold standards, clinical decisions made with the DELV-NR achieved high
      values on conventional measures of diagnostic accuracy. 

PMID- 24133300
TI  - Bone and Joint day - India.

PMID- 24133301
TI  - Outcome of distraction interference arthrodesis of the sacroiliac joint for
      sacroiliac arthritis.
AB  - BACKGROUND: After lumbar or lumbosacral fusion for various spine disorders,
      adjacent segment disease has been reported. Most of the studies have focused on
      proximal segment disease. The author has reported sacroiliac joint degeneration
      in these patients. Based on our own experiences with an increasing number of
      patients with sacroiliac joint (SIJ) arthralgia after multi-level lumbar or
      lumbosacral fusion procedures, we evaluated a surgical procedure called
      distraction arthrodesis of the SIJ for patients with refractory severe pain of
      the SIJ. MATERIALS AND METHODS: Nineteen (19) consecutive patients were recruited
      and evaluated prospectively after undergoing distraction arthrodesis of the SIJ.
      The inclusion criteria for the surgical procedure were degeneration of the SIJ
      and failed conservative treatment. Magnetic resonance imaging (MRI) scans and CT
      scans were performed in all cases. The clinical outcome was assessed using the
      Visual Analog Scale and the Oswestry Disability Index (ODI). CT scans were
      performed postoperatively and again at the final followup to evaluate assess
      fusion. The data was analyzed using the SPSS software (version 10.0; SPSS,
      Chicago, IL) and statistical analysis was performed. The P values were based on
      the Student t-test. RESULTS: The mean followup was 13.2 months. All patients had
      an instrumented lumbar or lumbosacral fusion. The overall fusion rate of SIJ was
      78.9% (15/19 joints). All patients demonstrated significant improvement in VAS
      and ODI scores compared to preoperative values. The mean VAS score was 8.5 before
      surgery and was 6 at final followup, demonstrating 30% improvement. The mean ODI
      scores were 64.1 before surgery and 56.97 at the final followup, demonstrating
      12% improvement. CONCLUSIONS: Refractory sacroiliac pain as a result of multi
      level fusion surgery can be successfully treated with minimally invasive
      arthrodesis. It offers a safe and effective treatment for severe SIJ pain.
      Careful patient selection is important.

PMID- 24133302
TI  - Head size and dislocation rate in primary total hip arthroplasty.
AB  - BACKGROUND: Dislocation after total hip arthroplasty (THA) has a multifactorial
      etiology with variables such as surgical approach, component orientation and
      position, type of cup, stem and head size. Review of the literature regarding the
      relationship of head size and dislocation rate in THA is suggestive that large
      femoral head size is associated with lower dislocation rate after THA. However,
      limited data is available as a proof of this hypothesis. The purpose of this
      study was to determine that the use of large head size would lead to a decreased
      incidence of dislocations following THA. MATERIALS AND METHODS: 317 primary THAs
      were performed using the posterolateral approach with posterior soft-tissue
      repair between January 2006 and December 2009. Cases were divided into two groups
      (A and B). Femoral head diameter size 36 mm was used in 163 THA in group A and 28
      mm in 154 THA in group B. Average period of followup being 2 years (6 month to 4
      years). Patients were routinely followed at definite intervals and were
      specifically assessed for dislocation. RESULTS: One or more dislocations occurred
      in 11 out of 317 hips with the overall rate of dislocation being 3.47%.
      Dislocation rate was 0.6% in 36 mm head size and 6.49% with 28 mm head size (P
      value is 0.0107). Keeping the stem design variable as a constant, the difference
      in the rate of dislocation between the two groups was again found to be
      statistically significant for both un-cemented and cemented stem. CONCLUSION:
      Dislocation rate decreased significantly as the size of the head increased in
      primary THA. However, longer followup is necessary as rate of dislocation or in
      vivo highly cross linked poly failure or fracture may increase in future
      affecting the rate of dislocations in primary THA.

PMID- 24133303
TI  - Revision hip arthroplasty as a treatment of Vancouver B3 periprosthetic femoral
      fractures without bone grafting.
AB  - BACKGROUND: It is conventionally considered that bone grafting is mandatory for
      Vancouver B3 periprosthetic femoral fractures (PFF) although few clinical studies
      have challenged the concept previously. The aim of the current study was to
      investigate the radiographic and functional results of Vancouver B3 PFF treated
      by revision total hip or hemiarthroplasty (HA) in combination with appropriate
      internal fixation without bone grafting. MATERIALS AND METHODS: 12 patients with
      Vancouver B3 PFF were treated by revision THA/HA without bone grafting between
      March 2004 and May 2008. There were nine females and three males, with an average
      age of 76 years. PFFs were following primary THA/HA in nine patients and
      following revision THA/HA in three. Postoperative followup was 5.5 years on
      average (range, 3.5-6.5 years). At the final followup, radiographic results were
      evaluated with Beals and Tower's criteria and functional outcomes were evaluated
      using the Merle d'Aubigne scoring system. RESULTS: All fractures healed within an
      average of 20 weeks (range, 12-28 weeks). There was no significant deformity and
      shortening of the affected limb and the implant was stable. The average Merle
      d'Aubigne score was 15.8. Walking ability was regained in 10 patients without
      additional assistance, while 2 patients had to use crutches. There were 2
      patients with numbness of lateral thigh, possibly due to injury to the lateral
      femoral cutaneous nerve. There were no implant failures, dislocation and
      refractures. CONCLUSIONS: Revision THA/HA in combination with appropriate
      internal fixation without bone grafting is a good option for treatment of
      Vancouver B3 periprosthetic femoral fractures in the elderly.

PMID- 24133304
TI  - Results of titanium locking plate and stainless steel cerclage wire combination
      in femoral fractures.
AB  - BACKGROUND: Some in vitro studies warn combining different metals in orthopedic
      surgery. The aim of this study is to determine the impact of combining titanium
      and stainless steel on bone healing and the clinical course of patients
      undergoing internal fixation of femoral fractures. MATERIALS AND METHODS: 69
      patients with femoral fractures had polyaxial locking plate osteosynthesis. The
      locking plate was made of a titanium alloy. Two different cohorts were defined:
      (a) sole plating and (b) additional stainless steel cerclage wiring.
      Postoperative radiographs and clinical followup were performed at 6 weeks, 3
      months and 12 months. RESULTS: Cohorts A and B had 36 and 33 patients,
      respectively. Patient demographics and comorbidities were similar in both groups.
      In two cases in cohort A, surgical revision was necessary. No complication could
      be attributed to the combination of titanium and stainless steel. CONCLUSION: The
      combination of stainless steel cerclage wires and titanium plates does not
      compromise fracture healing or the postoperative clinical course.

PMID- 24133305
TI  - Outcome of unicompartmental knee arthroplasty in octogenarians with
      tricompartmental osteoarthritis: A longer followup of previously published
      report.
AB  - BACKGROUND: Unicompartmental knee arthroplasty (UKA) has specific indications,
      producing excellent results. It, however, has a limited lifespan and needs
      eventual conversion to total knee arthroplasty (TKA). It is, therefore, a
      temporizing procedure in select active young patients with advanced
      unicompartmental osteoarthritis (UCOA). Being a less morbid procedure it is
      suggested as an alternative in the very elderly patients with tricompartmental
      osteoarthritis (TCOA). We performed UKA in a series of 45 octogenarians with TCOA
      predominant medial compartment osteoarthritis (MCOA) and analyzed the results.
      MATERIALS AND METHODS: Forty five octogenarian patients with TCOA predominant
      MCOA underwent UKA (19 bilateral) from January 2002 to January 2012. All had
      similar preoperative work-up, surgical approach, procedure, implants and
      postoperative protocol. Clinicoradiological assessment was done at 3-monthly
      intervals for the first year, then yearly till the last followup (average 72
      months, range 8-128 months). Results were evaluated using the knee society scores
      (KSS), satisfaction index [using the visual analogue scale (VAS)] and orthogonal
      radiographs (for loosening, subsidence, lysis or implant wear). Resurgery for any
      cause was considered failure. RESULTS: Four patients (six knees) died due to
      medical conditions, two patients (three knees) were lost to followup, and these
      were excluded from the final analysis. Barring two failures, all the remaining
      patients were pain-free and performing well at the final followup. Indications
      for resurgery were: medial femoral condyle fracture needing fixation subsequent
      conversion to TKA at 2 years (n=1) and progression of arthritis and pain leading
      to revision TKA at 6 years (n=1). CONCLUSION: UKA has shown successful outcomes
      with regards to pain relief and function with 96.4% implant survival and 94.9%
      good or excellent outcomes. Due to lower demands, early rehabilitation, less
      morbidity, and relative short life expectancy, UKA can successfully manage TCOA
      in the octogenarians.

PMID- 24133306
TI  - Outcomes of total knee arthroplasty following high tibial osteotomy.
AB  - BACKGROUND: Total knee arthroplasty (TKA) following high tibial osteotomy (HTO)
      is a technically demanding procedure with varying results. The purpose of our
      study was to analyze the clinicoradiological results of TKA following HTO and to
      identify the factors that may influence the final outcome. MATERIALS AND METHODS:
      55 patients (58 knees) who had undergone a previous HTO were treated with a TKA
      from 1991 to 2009. There were 34 female and 21 male patients. The average age was
      61.9 years (range 52-82 years) and the average weight was 79.5 kg (range 54-106
      kg), with an average body mass index of 29.6 (range 21.8-34.6) at the time of
      TKA. The knee society scores (KSSs) and knee society functional scores were
      evaluated for every patient pre and postoperatively and the results evaluated.
      RESULTS: The mean period of followup was 11.2 years (range 3-18 years) and the
      patients were followed up every year. The average KSS score at final followup
      improved from 38.5 (range 0-80 points) preoperatively to 88.5 postoperatively
      (range 35-95 points) (P < 0.05). The mean femorotibial angle corrected from 6.8
      degrees (range 5-12 degrees ) varus preoperatively to a valgus of 4.4 (2-8
      degrees ) degrees postoperatively. The average joint line height improved to an
      average of 9.6 mm (range 4.4-22 mm) (P < 0.01) at the last followup. The average
      Insall Salvatti Ratio also improved (average 1.11 preoperative - 1.21 average
      postoperative) (P < 0.05). The average range of motion improved to 108 degrees 
      (range 85 degrees -125 degrees ) from 76 degrees  preoperative (range 55 degrees 
      100 degrees ) (P < 0.01). CONCLUSION: Although TKA postHTO is a demanding surgery
      however, with newer component designs, results are comparable to primary TKA.
      Technical difficulties in exposure can sometimes lead to component
      malpositioning, which can affect the final outcome. Inadequate soft tissue
      balancing and limb malalignment should always be kept in mind. Regular followup
      to look for evidences of loosening is advised in such patients].

PMID- 24133307
TI  - Hemostatic matrix effects on blood loss after total knee arthroplasty: A
      randomized controlled trial.
AB  - BACKGROUND: Total knee arthroplasty (TKA) can result in major postoperative blood
      loss which can impact on the recovery and rehabilitation of patients. It also
      requires expensive transfusions. The purpose of the study was to investigate
      whether a hemostatic matrix, composed of cross-linked gelatin and a thrombin
      solution, would reduce blood loss in patients following TKA. MATERIALS AND
      METHODS: THIS WAS A PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY (TRIAL
      REGISTRATION: Hospital S. Salvatore L'Aquila ADJ00843) conducted in 93 patients.
      Criteria for participation were unilateral TKA for osteoarthritis, and a
      preoperative hemoglobin level >13 g/dL. The outcomes measured were postoperative
      hemoglobin and hematocrit levels measured at 24h, 72 h, and 7 days. The mean
      total postoperative blood loss was calculated from drainage volume, patient blood
      volume, hematocrit, and red blood cell volume. In addition, the drain output
      within 24 h following surgery and any transfusion requirements were determined.
      RESULTS: Hemostatic matrix-treated patients (n = 51) showed significant
      reductions in calculated postoperative blood loss of 32.3% and 28.7% versus
      control in men and women, respectively (P < 0.01). Postoperative blood loss after
      24 h in drain was significantly less with the hemostatic matrix versus control,
      as were decreases in hemoglobin levels 7 days post-surgery (each P < 0.01). Three
      patients in the control group required blood transfusion, whereas no blood
      transfusions were necessary in the hemostatic matrix group. CONCLUSION: The use
      of a hemostatic matrix provides a safe and effective means to reduce blood loss
      and blood transfusion requirements in TKA.

PMID- 24133308
TI  - False negative rate of syndesmotic injury in pronation-external rotation stage IV
      ankle fractures.
AB  - BACKGROUND: To investigate false negative rate in the diagnosis of diastasis on
      initial static anteroposterior radiograph and reliability of intraoperative
      external rotational stress test for detection of concealed disruption of
      syndesmosis in pronation external rotation (PER) stage IV (Lauge-Hansen) ankle
      fractures. MATERIALS AND METHODS: We prospectively studied 34 PER stage IV ankle
      fractures between September 2001 and September 2008. Twenty (59%) patients show
      syndesmotic injury on initial anteroposterior radiographs. We performed an
      intraoperative external rotation stress test in other 14 patients with suspicious
      PER stage IV ankle fractures, which showed no defined syndesmotic injury on
      anteroposterior radiographs inspite of a medial malleolar fracture, an oblique
      fibular fracture above the syndesmosis and fracture of the posterior tubercle of
      the tibia. RESULTS: All 14 fractures showed different degrees of tibiofibular
      clear space (TFCS) and tibiofibular overlapping (TFO) on the external rotation
      stress test radiograph compared to the initial plain anteroposterior radiograph.
      It is important to understand the fracture pattern characterstic of PER stage IV
      ankle fractures even though it appears normal on anteroposterior radiographs, it
      is to be confirmed for the concealed syndesmotic injury through a routine
      intraoperative external rotational stress radiograph.

PMID- 24133309
TI  - The operative treatment of complex pilon fractures: A strategy of soft tissue
      control.
AB  - BACKGROUND: Pilon fractures are challenging to manage because of the complexity
      of the injury pattern and the risk of significant complications. The soft tissue
      injury and handling of the soft tissue envelope are crucial in pilon fracture
      outcomes. The purpose of this study was to evaluate the early rate of
      complications using the strategy of "soft tissue control" for operative treatment
      of complex pilon fractures. MATERIALS AND METHODS: 36 complex pilon fractures
      were treated with the "soft tissue control" strategy. Patients followed the
      standard staged protocol, anterolateral approach to the distal tibia, the "no
      touch" technique and incisional negative pressure wound therapy for pilon
      fractures. Patients were examined clinically at 2-3 weeks and then 8 weeks for
      complications associated with the surgical technique. RESULTS: All fractures were
      AO/OTA (Orthopaedic Trauma Association) type C fractures (61% C3, 22% C2 and 16%
      C1). Only one patient developed superficial infection and resolved with
      antibiotics and local wound care. None developed deep infection. CONCLUSIONS: The
      strategy of soft tissue control for treatment of pilon fractures resulted in
      relatively low incidence of early wound complications in patients with complex
      pilon fractures.

PMID- 24133310
TI  - Effect of partial and complete posterior cruciate ligament transection on medial
      meniscus: A biomechanical evaluation in a cadaveric model.
AB  - BACKGROUND: The relationship between medial meniscus tear and posterior cruciate
      ligament (PCL) injury has not been exactly explained. We studied to investigate
      the biomechanical effect of partial and complete PCL transection on different
      parts of medial meniscus at different flexion angles under static loading
      conditions. MATERIALS AND METHODS: TWELVE FRESH HUMAN CADAVERIC KNEE SPECIMENS
      WERE DIVIDED INTO FOUR GROUPS: PCL intact (PCL-I), anterolateral bundle
      transection (ALB-T), posteromedial bundle transection (PMB-T) and PCL complete
      transection (PCL-T) group. Strain on the anterior horn, body part and posterior
      horn of medial meniscus were measured under different axial compressive tibial
      loads (200-800 N) at 0 degrees , 30 degrees , 60 degrees  and 90 degrees  knee
      flexion in each groups respectively. RESULTS: Compared with the PCL-I group, the
      PCL-T group had a higher strain on whole medial meniscus at 30 degrees , 60
      degrees  and 90 degrees  flexion in all loading conditions and at 0 degrees 
      flexion with 400, 600 and 800 N loads. In ALB-T group, strain on whole meniscus
      increased at 30 degrees , 60 degrees  and 90 degrees  flexion under all loading
      conditions and at 0 degrees  flexion with 800 N only. PMB-T exihibited higher
      strain at 0 degrees  flexion with 400 N, 600 N and 800 N, while at 30 degrees 
      and 60 degrees  flexion with 800 N and at 90 degrees  flexion under all loading
      conditions. CONCLUSIONS: Partial PCL transection triggers strain concentration on
      medial meniscus and the effect is more pronounced with higher loading conditions
      at higher flexion angles.

PMID- 24133311
TI  - Effects of montelukast sodium on tendon healing: An experimental study.
AB  - INTRODUCTION: Montelukast sodium (MS) a selective leukotriene antagonist of the
      cysteinyl leukotriene receptor, has been used in the treatment of asthma and
      allergic rhinitis. In this study, we evaluated the effect of MS on the early
      inflammatory phase (histological) of nonsynovial tendon healing. MATERIALS AND
      METHODS: Rats were divided randomly into two groups (n = 6 each). MS (Singulair)
      was administered to one group at 10 mg/kg/day [250 g/day intraperitoneally
      (i.p.)]. The control group was administered 250 g/day of 0.9% saline i.p. This
      nonsynovial tendon was longitudinally divided at the midportion, cut transversely
      and then sutured. In both groups, the rats were sacrificed by decapitation 10
      days later. RESULTS: Decreased inflammatory cell infiltration and more properly
      oriented collagen fibres were observed in the MS group's histopathological
      specimens as compared to the control group's (P < 0.05). Additionally,
      vascularity was decreased in the MS group. CONCLUSION: MS decreased tendon
      healing, apparently by inhibiting the early inflammatory phase of nonsynovial
      tendon healing.

PMID- 24133312
TI  - ISHKS joint registry: A preliminary report.
AB  - BACKGROUND: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are
      the most widely practiced surgical options for arthritis all over the world and
      its application is rising in India. Indian Society of Hip and Knee Surgeons
      (ISHKS) has established a joints registry and has been collecting data for last 6
      years. MATERIALS & METHODS: All members of ISHKS are encouraged to actively
      participate in the registry. A simple two page knee and hip form can be
      downloaded from the website www.ishks.com. The information collected includes
      patient demographics, indication for surgery, implant details and in case of
      revision arthroplasty: the details of implants removed and the cause of failure
      of primary arthroplasty. These forms are mailed to the central registry office
      and the data is fed in computerized registry. Data collection started in October
      2006. RESULTS: Joint registry is a very important initiative of ISHKS and till
      date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across
      India. Some important observations have emerged. Data of 34,478 TKAs was
      assessed: These included 8612 males (25%) and 25,866 females (75%). Average age
      was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range:
      22 to 74 years). Average body mass index was 29.1 (Range: 18.1 to 42.9). The
      indication for TKA was osteoarthritis in 33,444 (97%) and rheumatoid arthritis in
      759 (2.2%). Total of 3604 THA procedures were recorded. These included 2162 (60%)
      male patients and 1442 (40%) female patients. Average age was 52 years (Range 17
      to 85 years) and average BMI was 25.8 (Range: 17.3 to 38.5). The indications for
      THA was AVN in 49%. CONCLUSION: The registry will become more meaningful in years
      to come. Active participation of all arthroplasty surgeons across India is vital
      for the success of the joints registry.

PMID- 24133313
TI  - Modified valgus osteotomy of the femoral neck for late presenting femoral neck
      stress fractures in military recruits.
AB  - Neglected or late presenting femoral neck stress fractures are often associated
      with varus deformity, with potential risks of nonunion and osteonecrosis. We
      proposed a surgical technique whereby a wedge osteotomy was performed at the
      basal part of the neck, on the tensile surface, keeping the inferomedial femoral
      neck as a hinge. The femoral shaft was abducted to close the osteotomy site and
      it was fixed with three cannulated cancellous screws. Three military recruits who
      presented with neglected femoral neck stress fracture with varus deformity were
      operated on with the proposed modified femoral neck valgus osteotomy. All the
      fractures united without any complications and the patients resumed their
      professional activity. 

PMID- 24133314
TI  - Percutaneous osteoplasty in treatment of bone lymphangiomatosis.
AB  - Primary bone lymphangiomatosis is a disease of unknown etiology that can cause
      lytic lesions in long bones, the pelvis, the spinal column and the cranium. We
      are presenting the case of a woman with localized bone lymphangiomatosis in the
      left knee. The authors believe this is the first case in which percutaneous
      osteoplasty was used in long bones for the treatment of bone lesions resulting
      from this disease showing good clinical results. 

PMID- 24133315
TI  - Bioball universal modular neck adapter as a salvage for failed revision total hip
      arthroplasty.
AB  - Management of recurrent dislocation of total hip arthroplasty is often a
      challenging and daunting task. Re-revision of such a total hip prosthesis may not
      be easy as the removal of a well-fixed, fully coated stem is extremely difficult.
      We managed to salvage instability in three revision hip cases in which the fully
      coated stem had subsided by using a bioball universal neck adapter without
      changing the femoral stem or acetabular cup. 

PMID- 24133316
TI  - Osseous involvement in rhinosporidiosis.
AB  - Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium
      seeberi. It usually affects the mucocutaneous tissue of the nose. Bone
      involvement is rare. We report a case of Rhinosporidiosis of the nasopharynx
      which later involved the right little finger where ray amputation was performed. 

PMID- 24133317
TI  - Fungal prosthetic joint infection after total knee arthroplasty.
AB  - Fungal prosthetic joint infection after total knee arthroplasty (TKA) is a rare
      complication. Lacunae exist in the management of this complication. 62 year old
      lady presented with pain and swelling in left knee and was diagnosed as Candida
      tropicalis fungal infection after TKA. She underwent debridement, resection
      arthroplasty and antifungal plus antibiotic loaded cement spacer insertion,
      antifungal therapy with fluconazole followed by delayed revision TKA and further
      fluconazole therapy. Total duration of fluconazole therapy was 30 weeks. At 2
      year followup, she has pain less range of motion of 10( degrees )-90( degrees )
      and there is no evidence of recurrence of infection. 

PMID- 24133318
TI  - Intrathoracic displacement of the humeral head in a trauma patient.

PMID- 24133319
TI  - Author's reply.

PMID- 24133320
TI  - Four quadrant parallel peripheral screw fixation for displaced femoral neck
      fractures in elderly patients.

PMID- 24133321
TI  - Author's reply.

PMID- 24133322
TI  - Outcome of locking compression plates in humeral shaft nonunions.

PMID- 24133323
TI  - Author's reply.

PMID- 24133325
TI  - Acute kidney injury in critically ill children: More than just urine output.

PMID- 24133324
TI  - Bedside ultrasound and echocardiography by the pediatric intensivist: An evolving
      tool and a feasible option in a pediatric ICU.

PMID- 24133326
TI  - Methicillin-resistant Staphylococcus aureus carriage screening in intensive care.

PMID- 24133327
TI  - Clinical profile of acute kidney injury in a pediatric intensive care unit from
      Southern India: A prospective observational study.
AB  - BACKGROUND: Although the term acute renal failure was replaced by acute kidney
      injury (AKI) recently, there is a paucity of data on the incidence and profile of
      AKI in critically ill children from the developing world. OBJECTIVES: The
      objective of this study is to determine the incidence, etiology, short term
      outcome and predictors of fatality in critically ill children admitted to the
      pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.
      MATERIALS AND METHODS: In this prospective observational study, from June 2010 to
      March 2011, 215 children admitted to the PICU were screened for AKI, defined
      according to the AKI Network criteria. The patients with AKI were followed-up
      until discharge/death. Their clinical and biochemical data were recorded.
      RESULTS: The incidence of AKI among 215 patients screened was 54 (25.1%). The
      common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%),
      snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive
      cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted
      26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus,
      tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients
      required dialysis. Overall mortality was 46.3%. On logistic regression analysis,
      requirement of mechanical ventilation was an independent predictor of fatality in
      AKI. CONCLUSIONS: Besides the high incidence of AKI in critically ill-children
      admitted to the PICU (25.1%), the condition was associated with adverse outcomes,
      including high mortality (46.3%) and need for dialysis (27.8%). Infections
      dominated the etiological profile. Requirement of mechanical ventilation
      predicted an adverse outcome in our patient population.

PMID- 24133328
TI  - Association of biofilm production with multidrug resistance among clinical
      isolates of Acinetobacter baumannii and Pseudomonas aeruginosa from intensive
      care unit.
AB  - BACKGROUND AND AIMS: Given choice, bacteria prefer a community-based, surface
      bound colony to an individual existence. The inclination for bacteria to become
      surface bound is so ubiquitous in diverse ecosystems that it suggests a strong
      survival strategy and selective advantage for surface dwellers over their free
      ranging counterparts. Virtually any surface, biotic or abiotic (animal, mineral,
      or vegetable) is suitable for bacterial colonization and biofilm formation. Thus,
      a biofilm is "a functional consortium of microorganisms organized within an
      extensive exopolymeric matrix." MATERIALS AND METHODS: The present study was
      undertaken to detect biofilm production from the repertoire stocks of
      Acinetobacter baumannii (A. baumannii) and Pseudomonas aeruginosa (P. aeruginosa)
      obtained from clinical specimens. The tube method was performed to qualitatively
      detect biofilm production. RESULTS: A total of 109 isolates of both organisms
      were included in the study, out of which 42% (46/109) isolates showed biofilm
      detection. Among the biofilm producers, 57% of P. aeruginosa and 73% of A.
      baumannii showed multidrug resistance (MDR) pattern which was statistically
      significant in comparison to nonbiofilm producers (P < 0.001). CONCLUSION: To the
      best of our knowledge, this is the only study to have tested the biofilm
      production in both P. aeruginosa and A. baumannii in a single study. Biofilm
      production and MDR pattern were found to be significantly higher in A. baumannii
      than P. aeruginosa. Antibiotic resistance was significantly higher among biofilm
      producing P. aeruginosa than non producers. Similarly, antibiotic resistance was
      significantly higher among biofilm producing A. baumannii than non producers.

PMID- 24133329
TI  - Factors associated with death and predictors of 1-month mortality in nontraumatic
      coma in a tertiary hospital in Northwestern Nigeria.
AB  - BACKGROUND: Coma occurring in the course of an illness ordinarily implies a poor
      prognosis and early prognostication is important for treatment decisions. The
      study was undertaken to study the factors associated with mortality in
      nontraumatic coma in a tertiary institution. MATERIALS AND METHODS: In this
      prospective observational study, adults with clinically confirmed coma Glasgow
      coma scale (GCS) score of <=8, admitted consecutively to the emergency unit of a
      tertiary hospital in Northwestern Nigeria over a period of 18 months were
      recruited. Vital parameters, severity of coma by GCS and neurological signs were
      recorded. The etiology of coma was determined on the basis of history, clinical
      examination, and laboratory investigations. Outcome was determined within 1 month
      of onset of coma by patients' death or survival. RESULTS: A total of 194 patients
      (140 males and 54 females) were recruited with mean age was 53.7 +/- 1.4. The
      predominant etiological factors were central nervous system (CNS) infections
      (28.9%), toxic and metabolic (28.9%), and stroke (23.7%). Overall, 1-month
      mortality was 49%. On univariate analysis, the factors that showed significant
      association with outcome were gender, blood pressure, GCS, breathing pattern,
      pupillary size, pupillary reaction, papiloedema, and abnormal posturing. Abnormal
      pupillary size, severe hypertension, and GCS score <=5 were independent
      predictors of in-hospital 1-month mortality in nontraumatic coma. CONCLUSION: The
      independent important predictors of nontraumatic 1-month coma mortality in a
      developing country setting were GCS <= 5, abnormal pupillary size, and severe
      hypertension.

PMID- 24133330
TI  - Bedside echocardiography is useful in assessing children with fluid and inotrope
      resistant septic shock.
AB  - OBJECTIVE: To report changes in the cardiovascular management of fluid and
      inotropic resistant septic shock in children based on echocardiography. DESIGN:
      Retrospective case series. SETTING: Tertiary care Pediatric Intensive Care Unit
      (PICU), Chennai. PATIENTS: Twenty-two patients with unresolved septic shock after
      60 ml/kg fluid plus inotropic agents in the first hour. INTERVENTIONS: Bedside
      echocardiography (echo) within 6 h of admission to the PICU. RESULTS: Over a 28
      month period, of 37 patients with septic shock, 22 children remained in shock
      despite 60 ml/kg fluid and dopamine and/or dobutamine infusions as per
      guidelines. On clinical exam, 12 patients had warm shock and ten had cold shock,
      however, six exhibited an unusual pattern of cold shock with wide pulse pressures
      on invasive arterial monitoring. The most common echocardiographic finding was
      uncorrected hypovolemia in 12/22 patient while ten patients had impaired left +/-
      right ventricular function. Echocardiography permitted an appreciation of the
      underlying disordered pathophysiology and a rationale for adjustment of
      treatment. Shock resolved in 17 (77%) and 16 patients (73%) survived to
      discharge. CONCLUSIONS: Bedside echo provided crucial information that was not
      apparent on clinical assessment and affords a simple noninvasive tool to
      determine the cause of low cardiac output in patients who remain in shock despite
      60 ml/kg fluid and inotropic support. Most patients in our series had
      vasodilatory shock with wide pulse pressures and most common finding on echo was
      uncorrected hypovolemia. The echo findings allowed adjustment of therapy which
      was not possible based on clinical examination alone.

PMID- 24133331
TI  - Osmotic demyelination syndrome following slow correction of hyponatremia:
      Possible role of hypokalemia.
AB  - A 47-year-old male presented with hyponatremia that was corrected slowly as per
      the recommended guidelines. The patient improved initially but went on to develop
      a quadriparesis with a locked-in state due to a central as well as extrapontine
      myelinolysis and subsequently succumbed to an intercurrent infective illness. The
      patient had associated hypokalemia. Hyponatremia can result in central pontine
      myelinolysis even when the electrolyte disorder is treated slowly, and the
      concomitant hypokalemia seems to play a contributory role in the pathogenesis of
      the neurological disorder. 

PMID- 24133332
TI  - Thrombotic thrombocytopenic purpura secondary to ABO group incompatible blood
      transfusion in a patient after cardiac surgery.
AB  - The triggers of secondary thrombotic thrombopcytopenic purpura (TTP) include drug
      toxicity, radiation and high-dose chemotherapy, angioinvasive infections, surgery
      and acute graft versus host disease. TTP secondary to surgery have been reported
      in a number of cases. Most of the cases have been occurred after open heart
      surgery. Extensive endothelial damage is held responsible as the initiating
      mechanism in postoperative TTP cases. However, there is no report of secondary
      TTP describing development owing to ABO incompatible blood transfusion. Here, we
      describe a patient who developed TTP after transfusion of ABO incompatible blood
      during hospitalization for bypass surgery. We also propose a hypothesis which may
      account for the possible underlying mechanism. 

PMID- 24133333
TI  - Acute arterial thrombosis associated with inadvertent high dose of tranexamic
      acid.
AB  - Tranexamic acid (TA) act as anti-fibrinolytic agent and is widely used to limit
      bleeding in clinical practice. Tranexemic acid bind with plasminogen and prevent
      its conversion to plasmin, which limits the fibrinolytic pathway, so there is a
      theoretical risk of increasing thrombosis with high or prolonged therapy with TA.
      We encountered a case of acute arterial thrombosis following inadvertent
      administration of high dose of TA. A 27-years-old male with no other co-morbidity
      was ordered intravenous 1 gm TA to control excessive bleeding from previous
      bladder injury, but by mistake, he received 10 gm of TA. The patient developed
      signs and symptoms of acute ischemia in the right lower limb, which was diagnosed
      as acute iliac arterial thrombosis by computed tomography (CT) angiography. The
      patient was managed with systemic heparinization, fasciotomy for impending
      gangrene and other supportive care following which he recovered fully within a
      few days. Caution should be exercised for all prophylactic use, especially with
      high dosage or prolonged therapy with TA. 

PMID- 24133334
TI  - A new treatment modality for unilateral athelectasis: Recruitment maneuver with
      endobronchial blocker.
AB  - Atelectasis is a commonly seen complication during the post-operative period in
      intensive care units. The treatment of atelectasis depends on the underlying
      cause. We aimed to share our experience on the treatment of right total
      atelectasis in our intensive care unit applied with the help of the endobronchial
      blocker. 

PMID- 24133336
TI  - An observation of impact of neurological consultations in intensive care
      patients: Case series of 23 patients.
AB  - OBJECTIVE: The objective of the present study was to assess the impact of
      neurological consultation and intervention upon patient outcome in intensive care
      unit (ICU). SETTINGS: A retrospective observational study was conducted in the 24
      bedded multispecialty ICU of a 350 bedded tertiary care hospital over 8 months
      period, from January 2011 to August 2011. Critically, ill-patients with varied
      neurological symptomatology affecting the course of illness and ICU discharge
      were included. Neurological consult sought for, investigations ordered by the
      neurologist, interventions carried out, treatment started and the impact of such
      treatment on the outcome of patients were noted. The length of ICU stay was also
      noted. RESULTS: Over a period of 8 months, there were 864 ICU admissions. On
      neurological consult, 23 patients had a positive finding affecting the outcome: 5
      patients were diagnosed to have parkinson's disease, 4 patients had neuromuscular
      disease, 9 patients had high creatinine phosphokinase levels, 2 patients had
      restless legs syndrome and 3 patients were diagnosed to have seizure disorder.
      CONCLUSIONS: On being examined and investigated by neurologist, a variety of co
      existing neurological disorders could be diagnosed and if managed early, patients
      had a faster recovery, rapid weaning and early discharge from the ICU.

PMID- 24133335
TI  - Optimization of multiple muco-cutaneous site sampling method for screening MRSA
      colonization in ICU.
AB  - AIMS: Active screening for methicillin resistant Staphylococcus aureus (MRSA)
      carriers remains a vital component of infection control policy in any health-care
      setting. The relative advantage of multiple anatomical site screening for
      detecting MRSA carriers is well recognized. However, this leads to increase in
      financial and logistical load in a developing world scenario. The objective of
      our study was to determine the sensitivity of MRSA screening of nose, throat,
      axilla, groin, perineum and the site of catheterization (central line catheter)
      individually among intensive care unit patients and to compare it with the
      sensitivity of multiple site screening. MATERIALS AND METHODS: Active
      surveillance of 400 patients was done to detect MRSA colonization; 6 sites-nose,
      throat, axilla, perineum, groin and site of catheter were swabbed. RESULT AND
      DISCUSSION: The throat swab alone was able to detect maximum number of MRSA
      (76/90) carriers, with sensitivity of 84.4%. Next in order of sensitivity was
      nasal swab, which tested 77.7% of MRSA colonized patients. When multiple sites
      are screened, the sensitivity for MRSA detection increased to 95%. CONCLUSIONS:
      We found that though throat represent the most common site of MRSA colonization,
      nose or groin must also be sampled simultaneously to attain a higher sensitivity.

PMID- 24133337
TI  - The role of non-invasive positive pressure ventilation in post-extubation
      respiratory failure: An evaluation using meta-analytic techniques.
AB  - BACKGROUND: The use of non-invasive positive pressure ventilation (NIPPV) in post
      extubation respiratory failure is not well-established. Meta-analytic techniques
      were used to assess the effects of prophylactic application of NIPPV (prior to
      the development of respiratory failure) and therapeutic application of NIPPV
      (subsequent to the development of respiratory failure). MATERIALS AND METHODS:
      Randomized controlled trials (RCTs) from 1966 to May 2010 were identified using
      electronic databases. RCTs, which reported the use of NIPPV in post-extubation
      respiratory failure with defined assessable endpoints: reintubation, mortality
      and length of stay, were included. RESULTS: Reintubation was the primary outcome,
      mortality and lengths of stay were the secondary outcomes. Risk ratios (RR) were
      calculated for discrete outcomes and weighted mean differences (WMD) for
      continuous measures. There were 13 trials with 1420 patients; 9 prophylactic with
      861 patients and 4 therapeutic with 559 patients. In the prophylactic group,
      NIPPV was associated with lower rates of reintubation: RR 0.53 (95% confidence
      interval [CI], 0.28-0.98), P = 0.04. In the therapeutic group, NIPPV showed a
      null effect on reintubation: RR 0.79 (95% CI, 0.50-1.25), P = 0.31. The analysis
      on the secondary outcomes suggested significant reduction of hospital mortality
      with prophylactic application of NIPPV: RR 0.62 (95% CI 0.4-0.97), P = 0.03, with
      no effect on the other outcomes. Therapeutic application of NIPPV reduced
      intensive care unit length of stay: WMD -1.17 (95% CI -2.82 to -0.33), P = 0.006,
      but no effect on the other secondary outcomes. CONCLUSIONS: The results of this
      review suggested prophylactic NIPPV was beneficial with respect to reintubation
      and the therapeutic use of NIPPV showed a null effect.

PMID- 24133338
TI  - What is normal in an abnormality? Central venous cannulation in a patient with
      Situs inversus totalis with dextrocardia and polyCystic kidney disease.

PMID- 24133339
TI  - Metabolic alkalosis: A less appreciated side effect of Imipenem-cilastatin use.

PMID- 24133340
TI  - Intravenous lignocaine for treatment of refractory ileus following spinal cord
      injury.

PMID- 24133341
TI  - An unusual complication of internal jugular vein catheterization.

PMID- 24133342
TI  - Lesson of the seventh international congress on peer review and biomedical
      publication.

PMID- 24133344
TI  - Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3
      academic hospitals.
AB  - Social factors may affect the available sources of toxic substances and causes of
      poisoning; and these factors may change over time. Additionally, understanding
      the characteristics of patients with acute toxic poisoning is important for
      treating such patients. Therefore, this study investigated the characteristics of
      patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and
      2011 were included in this study. Data on all patients who were admitted to the
      emergency departments with acute toxic poisoning were retrospectively obtained
      from medical records. Total 939 patients were analyzed. The average age of
      patients was 40.0 +/- 20 yr, and 335 (36.9%) patients were men. Among the
      elements that did not change over time were the facts that suicide was the most
      common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and
      that there were more women than men. Furthermore, acetaminophen and doxylamine
      remained the most common poisoning agents. In conclusion, the average patient age
      and psychotic drug poisoning has increased over time, and the use of lavage
      treatment has decreased. 

PMID- 24133343
TI  - NLRP3 inflammasome and host protection against bacterial infection.
AB  - The inflammasome is a multi-protein complex that induces maturation of
      inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of
      caspase-1. Several nucleotide binding oligomerization domain-like receptor family
      members, including NLRP3, recognize unique microbial and danger components and
      play a central role in inflammasome activation. The NLRP3 inflammasome is
      critical for maintenance of homeostasis against pathogenic infections. However,
      inflammasome activation acts as a double-edged sword for various bacterial
      infections. When the IL-1 family of cytokines is secreted excessively, they cause
      tissue damage and extensive inflammatory responses that are potentially hazardous
      for the host. Emerging evidence has shown that diverse bacterial pathogens or
      their components negatively regulate inflammasome activation to escape the immune
      response. In this review, we discuss the current knowledge of the roles and
      regulation of the NLRP3 inflammasome during bacterial infections. Activation and
      regulation of the NLRP3 inflammasome should be tightly controlled to prevent
      virulence and pathology during infections. Understanding the roles and regulatory
      mechanisms of the NLRP3 inflammasome is essential for developing potential
      treatment approaches against pathogenic infections. 

PMID- 24133345
TI  - Patients with persistent new-onset diabetes after transplantation have greater
      weight gain after kidney transplantation.
AB  - The purpose of the present study was to evaluate the difference in BMI pattern
      between patients with persistent new-onset diabetes after transplantation (P
      NODAT) and without new-onset diabetes after transplantation (N-NODAT) in a
      retrospective matched case-control (1:3) analysis. Thirty-six patients who
      developed P-NODAT were identified among 186 adult renal transplant recipients
      with no evidence of pretransplant diabetes mellitus who underwent kidney
      transplantation from September 1997 to March 2008 and were treated with a triple
      regimen including tacrolimus. The controls were selected to match the patients
      for pretransplant BMI, age at transplantation (+/- 5 yr), and date of
      transplantation (+/- 12 months). Finally, 20 P-NODAT patients and 60 N-NODAT
      patients were selected. The pre- and posttransplant BMI data were collected every
      16 weeks for up to 80 weeks. The clinical characteristics did not differ between
      the P-NODAT group and N-NODAT group. BMI increased faster in the P-NODAT group
      than in the N-NODAT group. The mixed-model analysis showed that patients with P
      NODAT exhibited a faster increase in BMI. P-NODAT is associated with
      posttransplant weight gain. The risk of P-NODAT should be considered in patients
      with rapid weight gain after transplantation. 

PMID- 24133346
TI  - Expression of semaphorin 3A and neuropilin 1 in asthma.
AB  - Neuropilin 1 (NP1) is a part of essential receptor complexes mediating both
      semaphorin3A (SEMA3A) and vascular endothelial growth factor (VEGF) which is one
      of important mediators involved in the pathogenesis of asthma. Therefore, it is
      possible that SEMA3A plays a role in the pathogenesis of asthma through
      attenuation of VEGF-mediated effects. In the present study, we aimed to evaluate
      expression levels of SEMA3A and NP1 using induced sputum of asthmatics and a
      murine model of asthma. Firstly, SEMA3A and NP1 expressions in induced sputum of
      asthmatics and SEMA3A and NP1 expression on bronchoalveolar lavage (BAL) cells
      and lung homogenates of asthmatic mice were determined. Then we evaluated the
      immunolocalization of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), and NP1
      expressions on asthmatic mice lung tissue and their subcellular distributions
      using fibroblast and BEAS2B cell lines. Sputum SEMA3A and NP1 expressions were
      significantly higher in asthmatics than controls. Similarly, SEMA3A and NP1
      expressions on BAL cells and lung homogenates were significantly elevated in
      asthmatic mice compared to control mice. Immunohistochemical analysis showed that
      VEGFR1, VEGFR2, and NP1 expressions were also uniformly increased in asthmatic
      mice. Our observations suggest that SEMA3A and NP1 may play important roles in
      the pathogenesis of asthma. 

PMID- 24133347
TI  - Expression and clinicopathological significance of CD9 in gastrointestinal
      stromal tumor.
AB  - This study investigated the expression and clinicopathological significance of
      CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for
      CD9 was performed on tumor tissues from 74 GIST patients. The correlation with
      clinicopathological features, risk classification and prognosis was analyzed. CD9
      positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive
      expression rate of the sample was significantly associated with diameter (P =
      0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three
      year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards
      regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for
      post-operative RFS. The subgroup analysis showed that CD9 expression in gastric
      stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk
      classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional
      hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent
      factor for RFS of GST. However, CD9 expression does not have a statistically
      significant correlation with clinicopathological features, risk classification,
      and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be
      associated with the recurrence and/or metastasis of GIST patients, especially in
      GST, which may indicate the important role of CD9 in the malignant biological
      behavior and prognosis of GST. 

PMID- 24133348
TI  - Status of primary liver cancer found through routine health check-up.
AB  - This study aimed to investigate the status of primary liver cancers found through
      a routine health check-up. The data of subjects who were diagnosed with primary
      liver cancer for the first time through a routine health check-up during a period
      of 8-yr were analyzed. Primary liver cancers were detected for the first time in
      34 subjects among 91,219 routine health check-up subjects. Only 11.8% of primary
      liver cancer subjects had been under previous surveillance. Of them, 55.8% were
      positive for HBsAg, 17.7% were positive for anti-HCV, and 8.8% were heavy alcohol
      comsumers. However, 17.7% of the subjects were neither heavy alcohol consumers
      nor positive for both HBsAg and anti-HCV. Of the subjects, 50.0% had a single
      nodular tumor, 23.5% had multi-nodular tumors, and 26.5% had an infiltrative
      tumor. A routine health check-up may provide beneficial opportunities to detect a
      liver cancer in a very early stage. It is beneficial to start surveillance in
      high-risk subjects for liver cancer or to detect any liver cancer in subjects
      without risk factors of chronic viral hepatitis or heavy alcohol consumption. 

PMID- 24133349
TI  - Long QT syndrome: a Korean single center study.
AB  - The long QT syndrome (LQTS) is a rare hereditary disorder in which affected
      individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac
      death. We investigated 62 LQTS (QTc >= 0.47 sec) and 19 family members whose
      genetic study revealed mutation of LQT gene. In the proband group, the modes of
      presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and
      syncope or seizure (19.4%). Median age of initial symptom development was 10.5
      yr. Genetic studies were performed in 61; and mutations were found in 40 cases
      (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the
      family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as
      patients had the history of syncope (P = 0.001), ventricular tachycardia (P =
      0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut
      off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta
      blocker was frequently applied for treatment and had significant effects on
      reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in
      6 patients. Congenital LQTS is a potentially lethal disease. It shows various
      genetic mutations with low penetrance in Korean patients. 

PMID- 24133350
TI  - Association between central obesity and circadian parameters of blood pressure
      from the korean ambulatory blood pressure monitoring registry: Kor-ABP registry.
AB  - Central obesity has been reported as a risk for atherosclerosis and metabolic
      syndrome. The influence of central obesity on diurnal blood pressure (BP) has not
      been established. In this study, we investigated the influence of central obesity
      on the circadian parameters of BP by 24 hr ambulatory BP monitoring. Total 1,290
      subjects were enrolled from the Korean Ambulatory BP registry. Central obesity
      was defined as having a waist circumference>=90 cm in males and >=85 cm in
      females. The central-obese group had higher daytime systolic BP (SBP), nighttime
      SBP and diastolic BP (DBP) than the non-obese group (all, P<0.001). There were no
      differences in nocturnal dipping (ND) patterns between the groups. Female
      participants showed a higher BP mean difference (MD) than male participants with
      concerns of central obesity (daytime SBP MD 5.28 vs 4.27, nighttime SBP MD 6.48
      vs 2.72) and wider pulse pressure (PP). Central obesity within the elderly (>=65
      yr) also showed a higher BP MD than within the younger group (daytime SBP MD 8.23
      vs 3.87, daytime DBP 4.10 vs 1.59). In conclusion, central obesity has no
      influence on nocturnal dipping patterns. However, higher SBP and wider PP are
      associated with central obesity, which is accentuated in women. 

PMID- 24133351
TI  - A reverse dipping pattern predicts cardiovascular mortality in a clinical cohort.
AB  - An abnormal dipping pattern in ambulatory blood pressure monitoring (ABPM) is a
      cardiovascular (CV) risk factor. However, its impact on CV mortality has not been
      investigated sufficiently in clinical practice to be considered a standard
      parameter. We assessed the association between abnormal dipping patterns and
      increased CV mortality in a tertiary hospital in Korea. Our retrospective cohort
      study included 401 patients who underwent ABPM between 1994 and 1996 in Hanyang
      University Hospital, Seoul, Korea. The patients were classified as risers (<0%
      drop in systolic BP; n=107), and others included dippers and non-dippers (>=0%
      drop, n=294). The follow-up period was 120 months. The frequency of CV mortality
      was 14.0% in risers and 5.8% in others. A Cox regression analysis found a
      significant association between dipping pattern and CV mortality, after adjusting
      for age, gender, body mass index, hypertension, diabetes mellitus, smoking and
      hypercholesterolemia. Risers were at greater risk of CV death than others (RR,
      3.02, P=0.022), but there was no difference in event rates between dippers and
      non-dippers. The reverse dipping pattern may be more frequent in clinical
      settings than in the population at large, and it is strongly associated with
      increased risk of CV mortality in Korea. 

PMID- 24133352
TI  - S-Fas urinary excretion helps to predict the immunosuppressive treatment outcomes
      in patients with proliferative primary glomerulonephritis.
AB  - Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important
      role in glomerulonephritis (GN). The study assed the influence of
      immunosuppressive treatment on serum and urine sFas in patients with
      proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential
      of sFas measurements in predicting outcomes. Eighty-four patients with GN (45
      males and 39 females) were included. Serum concentration (ng/mL) and urinary
      excretion (ng/mg of urinary creatinine) of sFas were measured before and after
      the treatment. After 12 months of therapy with steroids and cyclophosphamide,
      patients were divided into two subgroups according to the treatment results:
      Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced
      after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008
      and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas
      serum concentration remained unchanged. In PGN, pre-treatment urinary sFas
      concentration was significantly lower in the Responders than in Non-Responders
      (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P
      = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment
      reduced sFas urinary excretion in proliferative and non-proliferative GN and
      results suggest that the lower urinary sFas may be linked with favorable therapy
      outcomes in patients with PGN. 

PMID- 24133353
TI  - Dairy product intake is inversely associated with metabolic syndrome in Korean
      adults: Anseong and Ansan cohort of the Korean Genome and Epidemiology Study.
AB  - The objective of this study was to examine the relationship between dairy product
      intake and the incidence of metabolic syndrome (MetS) and its components among
      middle-aged Koreans. We examined 7,240 adults aged 40-69 yr without MetS at
      baseline over a 45.5-month follow-up period. They were taken from the Anseong and
      Ansan cohort of the Korean Genome and Epidemiology Study. Dairy product intake
      including milk, yogurt, and cheese was assessed with food frequency
      questionnaire. At the follow-up, the incidence of MetS was 17.1%. The incidences
      of MetS components were as follows: low HDL cholesterol (16.2%), abdominal
      obesity (14.0%), hypertriglyceridemia (13.8%), hyperglycemia (13.3%), and
      hypertension (13.1%). Adjusting for potential confounders, dairy product
      consumption frequency was inversely associated with the risk of MetS and
      abdominal obesity. Hazard ratio (HR) (95% confidence interval) for dairy product
      consumption more than 7 times/week compared to never was 0.75 (0.64-0.88, P for
      trend < 0.001) for MetS and 0.73 (0.61-0.88, P for trend < 0.001) for abdominal
      obesity. HR for milk intake was 0.79 for MetS and 0.82 for abdominal obesity. The
      results of this study suggest that daily intake of dairy products protects
      against the development of MetS, particularly abdominal obesity, in middle-aged
      Koreans. 

PMID- 24133354
TI  - Genetic and clinical characteristics of korean patients with isolated
      hypoparathyroidism: from the Korean hypopara registry study.
AB  - Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused
      by defects in a variety of genes. The goal of our study was to determine the
      clinical features and to analyze gene mutations in a large cohort of Korean
      patients with sporadic or familial IH. We recruited 23 patients. They showed a
      broad range of onset age and various values of biochemical data. Whole exome
      sequencing was performed on two affected cases and one unaffected individual in a
      family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH
      were sequenced using PCR-amplified DNA. In one family who underwent the whole
      exome sequencing analysis, approximately 300 single nucleotide changes emerged as
      candidates for genetic alteration. Among them, we identified a functional
      mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous
      gain-of-function mutations in the CASR gene were found in other subjects; D410E
      and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro
      PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current
      study represents a variety of biochemical phenotypes in IH patients with the
      molecular genetic diagnosis of IH. 

PMID- 24133355
TI  - High serum osteopontin levels are associated with low bone mineral density in
      postmenopausal women.
AB  - Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the
      bone and kidneys. It is reportedly involved in bone resorption and formation. We
      examined the association between serum OPN levels and bone mineral density in
      postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409)
      participated in the study. We measured serum osteopontin levels and their
      relationships with bone mineral density and previous total fragility fractures.
      The postmenopausal women had higher mean serum OPN levels compared to the
      premenopausal women (43.6+/-25.9 vs 26.3+/-18.6 ng/mL; P<0.001). In the
      postmenopausal women, high serum OPN levels were negatively correlated with mean
      lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple
      linear regression model, serum OPN levels were associated with BMD of the spine,
      femoral neck, and total hip after adjustment for age, body mass index, smoking,
      and physical activity in postmenopausal women. However, serum OPN levels did not
      differ between postmenopausal women with and without fractures. Postmenopausal
      women exhibit higher serum OPN levels than premenopausal women and higher serum
      OPN levels were associated with low BMD in postmenopausal women. 

PMID- 24133356
TI  - Chronic kidney disease, hemodynamic instability, and endoscopic high-risk
      appearance are associated with 30-day rebleeding in patients with non-variceal
      upper gastrointestinal bleeding.
AB  - The results of studies that evaluated predictive factors for rebleeding in non
      variceal upper gastrointestinal bleeding are inconsistent. The aim of this study
      was to investigate predictive factors for 30-day rebleeding in these patients. A
      consecutive 312 patients presenting symptoms and signs of gastrointestinal
      bleeding were enrolled in this prospective, observational study. Clinical and
      demographic characteristics and endoscopic findings were evaluated for potential
      factors associated with 30-day rebleeding using logistic regression analysis.
      Overall, 176 patients were included (male, 80.1%; mean age, 59.7+/-16.0 yr).
      Rebleeding within 7 and 30 days occurred in 21 (11.9%) and 27 (15.3%) patients,
      respectively. We found that chronic kidney disease (CKD) (OR, 10.29; 95% CI, 2.84
      37.33; P<0.001), tachycardia (pulse>100 beats/min) during the admission (OR,
      3.79; 95% CI, 1.25-11.49; P=0.019), and Forrest classes I, IIa, and IIb (OR,
      6.14; 95% CI, 1.36-27.66; P=0.018) were significant independent predictive
      factors for 30-day rebleeding. However, neither Rockall nor Blatchford scores
      showed statistically significant relationships with 30-day rebleeding in a
      multivariate analysis. CKD, hemodynamic instability during hospitalization, and
      an endoscopic high-risk appearance are significantly independent predictors of 30
      day rebleeding in patients with non-variceal upper gastrointestinal bleeding.
      These factors may be useful for clinical management of such patients. 

PMID- 24133357
TI  - Hepatoportal sclerosis in childhood: descriptive analysis of 12 patients.
AB  - Hepatoportal sclerosis (HPS) is defined as sclerosis of portal areas in the
      absence of cirrhosis. There is little information about HPS in children in the
      literature. The aim of this study was to describe the clinical presentation,
      associated disorders, laboratory characteristics and outcome of children who were
      diagnosed as HPS. This study included 12 children diagnosed as HPS by the
      Pathology Department between 2005 and 2011. Data were collected from the
      gastroenterology clinic charts retrospectively, including demographics,
      presentation characteristics, laboratory data and recent status of patients.
      Twelve patients were enrolled (6 girls, 6 boys). The median age of patients was
      13.5 yr. Median age at the time of biopsy was 11 yr. Four patients had
      splenomegaly, 3 had esophageal varices, one had hepatopulmonary syndrome and had
      been transplanted. Smooth muscle antibody was found positive in 4 patients,
      without autoimmune hepatitis findings in liver biopsy. One patient had celiac
      disease and another patient had positive celiac disease serology but pathology
      findings. Another patient had Turner's syndrome. Mean follow-up time was 39
      months (3.3 yr) after biopsy. Hepatoportal sclerosis does not necessarily present
      with portal hypertension in children. 

PMID- 24133359
TI  - Tooth loss may predict poor cognitive function in community-dwelling adults
      without dementia or stroke: the PRESENT project.
AB  - Periodontal disease is a potential predictor of stroke and cognitive impairment.
      However, this association is unclear in adults aged 50 yr and above without a
      history of stroke or dementia. We evaluated the association between the number of
      teeth lost, indicating periodontal disease, and cognitive impairment in community
      dwelling adults without any history of dementia or stroke. Dental examinations
      were performed on 438 adults older than 50 yr (315 females, mean age 63+/-7.8 yr;
      123 males, mean age 61.5+/-8.5 yr) between January 2009 and December 2010. In the
      unadjusted analysis, odds ratios (OR) of cognitive impairment based on MMSE score
      were 2.46 (95% CI, 1.38-4.39) and 2.7 (95% CI, 1.57-4.64) for subjects who had
      lost 6-10 teeth and those who had lost more than 10 teeth, respectively, when
      compared with subjects who had lost 0-5 teeth. After adjusting for age, education
      level, hypertension, diabetes, hyperlipidemia, and smoking, the relationship
      remained significant (OR, 2.0; 95% CI, 1.08-3.69, P=0.027 for those with 6-10
      teeth lost; OR, 2.26; 95% CI, 1.27-4.02, P=0.006 for those with more than 10
      teeth lost). The number of teeth lost is correlated with cognitive impairment
      among community-dwelling adults aged 50 and above without any medical history of
      stroke or dementia. 

PMID- 24133358
TI  - Longitudinal standards for height and height velocity in Korean children and
      adolescents: the Kangwha study. [corrected].
AB  - Longitudinal standards for height and height velocity are essential to monitor
      for appropriate linear growth. We aimed to construct standards in Korean children
      and adolescents through the population-based longitudinal Kangwha study. Our
      study was a part of a community-based prospective cohort study from 1986 to 1999
      with 800 school children. Height and height velocity were recorded annually from
      age 6 until final height. Results were compared with cross-sectional data from
      the 2007 Korean National Growth Charts. Final height was 173.5 cm in boys and
      160.5 cm in girls. Although final height was similar between longitudinal and
      cross-sectional standards, the mean height for age was higher in the longitudinal
      standard by 1-4 cm from age 6 until the completion of puberty. Using the
      longitudinal standard, age at peak height velocity (PHV) was 12 in boys and 10 in
      girls; height velocity at PHV was 8.62 cm/yr in boys and 7.07 cm/yr in girls. The
      mean height velocity was less than 1 cm/yr at age 17 in boys and 15 in girls.
      Thus, we have presented the first report of longitudinal standards for height and
      height velocity in Korean children and adolescents by analyzing longitudinal data
      from the Kangwha cohort. 

PMID- 24133360
TI  - Improvement of dementia screening accuracy of mini-mental state examination by
      education-adjustment and supplementation of frontal assessment battery
      performance.
AB  - This study aimed to investigate whether the demographic variable-adjustment and
      supplementation of Frontal Assessment Battery (FAB) score can improve the
      screening ability of Mini-Mental State Examination (MMSE) for dementia and its
      subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia
      (320 Alzheimer's disease [AD]; 139 non-Alzheimer's disease dementia [NAD]; and 15
      mixed AD-NAD dementia) individuals living in the community were included.
      Education-adjusted MMSE (MMSE-edu) score showed significantly better screening
      accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented
      MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not
      for overall dementia and AD, than MMSE raw score alone. Additional
      supplementation of FAB to MMSE-edu further increased the ability for overall
      dementia or NAD screening, but not for AD screening. Further education adjustment
      of MMSE-FAB also improved its ability for overall dementia, AD, and NAD
      screening. These results strongly support the usefulness of education-adjustment
      and supplementation of frontal function assessment to improve screening
      performance of MMSE for dementia and its subtypes, NAD in particular. 

PMID- 24133361
TI  - Neural substrate responsible for crossed aphasia.
AB  - Crossed aphasia (CA) refers to language impairment secondary to right hemisphere
      lesion. Imaging analysis on the lesion location of CA has not yet been reported
      in the literature. This study was proposed to analyze the most prevalent lesion
      site related to CA. Brain MRI of 7 stroke patients satisfying the criteria for CA
      were used to define Region of interest (ROIs) before overlaying the images to
      visualize the most overlapped area. Talairach coordinates for the most overlapped
      areas were converted to corresponding anatomical regions. Anatomical lesions
      where more than 3 patients' images were overlapped were considered significant.
      The overlayed ROIs of 7 patients revealed the lentiform nucleus as the most
      frequently involved area, overlapping in 6 patients. Our study first demonstrates
      the areas involved in CA by lesion mapping using brain MRI, and lentiform nucleus
      is the responsible neural substrate for crossed aphasia. 

PMID- 24133362
TI  - Oropharyngeal Dysphagia in a community-based elderly cohort: the korean
      longitudinal study on health and aging.
AB  - This study was conducted to investigate the prevalence of dysphagia and evaluated
      the association of dysphagia and activities of daily living in a geriatric
      population residing in an independent-living facility in Korea. Korean men and
      women 65-yr and older living in a single, typical South Korean city (n=415) were
      enrolled in the Korean Longitudinal Study on Health and Aging study. Dysphagia
      was assessed using the Standardized Swallowing Assessment. Data were collected on
      activities of daily living (ADL), instrumental ADL (IADL), and medical history
      and laboratory. The overall prevalence of dysphagia in the random sample was
      33.7% (95% CI, 29.1-38.4), including 39.5% in men and 28.4% in women. The
      identified risk factors for dysphagia were men (OR, 3.6, P=0.023), history of
      stroke (OR, 2.7, P=0.042) and presence of major depressive disorder (OR, 3.0,
      P=0.022). Dysphagia was associated with impairment in IADL domains of preparing
      meals and taking medicine (P=0.013 and P=0.007, respectively). This is the first
      published report of the prevalence of dysphagia in older community-dwelling
      Koreans. Dysphagia is a common problem among elderly people that limits some IADL
      domains. 

PMID- 24133363
TI  - Case report of occupational asthma induced by polyvinyl chloride and nickel.
AB  - Polyvinyl chloride (PVC) is a widely used chemical for production of plastics.
      However occupational asthma (OA) caused by PVC has been reported only rarely. We
      report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel
      (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room
      due to an asthma attack with moderate airflow obstruction and markedly increased
      sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5
      mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late
      asthmatic responses, respectively. Moreover, the fractional concentration of
      exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our
      knowledge, this is the first case of OA in Korea induced by exposure to both PVC
      and Ni. We suggest that eosinophilic inflammation may be involved in the
      pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its
      diagnosis. 

PMID- 24133364
TI  - A case of extrinsic compression of the left main coronary artery secondary to
      pulmonary artery dilatation.
AB  - Extrinsic compression of the left main coronary artery (LMCA) secondary to
      pulmonary artery dilatation is a rare syndrome. Most cases of pulmonary artery
      hypertension but no atherosclerotic risk factors rarely undergo coronary
      angiography, and hence, diagnoses are seldom made and proper management is often
      delayed in these patients. We describe a patient that presented with pulmonary
      hypertension, clinical angina, and extrinsic compression of the LMCA by the
      pulmonary artery, who was treated successfully by percutaneous coronary
      intervention. Follow-up coronary angiography showed patent stent in the LMCA in
      the proximity of the dilated main pulmonary artery. This case reminds us that
      coronary angiography and percutaneous coronary intervention should be considered
      in pulmonary hypertension patients presenting with angina or left ventricular
      dysfunction. 

PMID- 24133365
TI  - Secondary prophylaxis of docetaxel induced diarrhea with loperamide: case report.
AB  - Diarrhea is a common adverse event of docetaxel with 20%-40% of incidence and
      severe diarrhea occurs in 5%-6%. Several treatment guidelines for chemotherapy
      induced diarrhea (CID) exist, however the prophylaxis for that is not well known.
      We describe a new prophylactic approach for the CID with loperamide. A 72-yr-old
      male patient with stage IV non-small-cell lung cancer developed diarrhea
      repeatedly after docetaxel-cisplatin chemotherapy. His diarrhea persisted despite
      treatment including loperamide and fasting. However, the diarrhea was
      successfully prevented when loperamide was given before and after the
      chemotherapy. To our knowledge, this is the first report of prophylactic approach
      for the CID with loperamide. 

PMID- 24133366
TI  - Epidemiology of hemorrhagic fever with renal syndrome in Korea, 2001-2010.
AB  - This study describes the epidemiology of hemorrhagic fever with renal syndrome
      (HFRS) in the past 10 yr (2001-2010) in Korea. During this period, a total of
      3,953 HFRS patients and an average prevalence rate of 0.81 per 100,000 population
      were recorded, with a total of 40 fatal cases, corresponding to a case fatality
      rate of 1.01%. More HFRS cases were found in men than in women (57% vs 43%), and
      a higher prevalence rate of HFRS was observed in patients older than 40 yr
      (82.1%). The highest numbers of HFRS cases were found amongst farmers (35.6%).
      The majority of HFRS cases (71.3%) occurred in the last quarter of the calendar
      year (October to December). More HFRS cases occurred in the western part than in
      the eastern part of Korea (68.9% vs 31.1%). The incidence of HFRS was
      significantly higher (P < 0.001) in rural areas than in urban areas (80.3% vs
      19.7%). HFRS still occurs commonly among men, in autumn, and in western rural
      area of Korea. 

PMID- 24133367
TI  - RET fusion genes in Korean non-small cell lung cancer.
AB  - Recently, rearranged during transfection (RET) fusions have been identified in
      approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of
      RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156
      surgically resected NSCLCs using a reverse transcriptase polymerase chain
      reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All
      three patients were females and never smokers with adenocarcinomas. RET fusion
      genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET
      fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in
      Koreans. 

PMID- 24133369
TI  - Phase II study of whole brain radiotherapy with or without erlotinib in patients
      with multiple brain metastases from lung adenocarcinoma.
AB  - The aim of this paper is to explore the efficacy of whole brain radiotherapy
      (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain
      metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both
      arms. In the combination arm, 150 mg erlotinib was given each day, starting the
      first day of radiotherapy and continuing for 1 month following the end of
      radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best
      supportive therapy was given to both arms. The intracranial objective response
      rate and the local progression-free survival (LPFS) were primary endpoints.
      Toxicity, progression-free survival (PFS) and overall survival (OS) were
      secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the
      combination group were enrolled from November 2009 to December 2011. In the WBRT
      and the combination arms, respectively, the objective response rate was 54.84%
      and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months
      and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P =
      0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the
      combination group, there were no differences of LPFS, PFS, and OS between the
      epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type
      patients. No Grade 4 or higher side effects were observed in either group. A
      multivariate analysis indicated that erlotinib was the most important prognostic
      factor for a prolonged survival. Data showed that erlotinib in combination with
      WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung
      adenocarcinoma patients with multiple brain metastases compared with WBRT
      monotherapy. 

PMID- 24133368
TI  - Comparison of enhanced depth imaging and high-penetration optical coherence
      tomography for imaging deep optic nerve head and parapapillary structures.
AB  - PURPOSE: To evaluate and compare the abilities of enhanced depth imaging (EDI)
      and high-penetration optical coherence tomography (HP-OCT) to visualize the deep
      optic nerve head (ONH) and deep parapapillary structures. METHODS: Horizontal and
      vertical optic nerve images were obtained using EDI-OCT and HP-OCT, during the
      same visit, from 24 eyes of 12 patients with glaucoma. Three graders, using a
      three-point grading system, independently graded the visibility of the deep ONH
      structures (prelaminar tissue surface, anterior laminar surface, posterior
      laminar border, and laminar pores) and deep parapapillary structures
      (intrascleral vessels, cerebrospinal fluid space, and parapapillary choroid). The
      differences in the visibility scores between the EDI-OCT and the HP-OCT images
      and among the image locations were analyzed statistically. The agreement in
      scoring among the graders also was analyzed. RESULTS: The visibility of three ONH
      structures, the anterior laminar surface, posterior laminar border, and laminar
      pores, was significantly better with EDI-OCT (P = 0.0010, P < 0.0001, and P =
      0.0141, respectively). In contrast, the visibility of all parapapillary
      structures was significantly better with HP-OCT (P < 0.0001, P = 0.0176, and P <
      0.0001, respectively). The visibility scores were better in the vertical images
      compared with the horizontal images and were best in the temporal quadrants. The
      intergrader agreement was moderate for all parameters examined. CONCLUSION: Both
      EDI-OCT and HP-OCT are useful for evaluating the deep ONH and parapapillary
      structures. The visibility scores of the deep ONH structures were better with EDI
      OCT, in contrast to the better visibility scores of the deep parapapillary
      structures with HP-OCT. Both systems should be chosen depending on the target
      tissue to observe.

PMID- 24133370
TI  - "Expiratory holding" approach in measuring end-expiratory pulmonary artery wedge
      pressure for mechanically ventilated patients.
AB  - OBJECTIVE: To accurately measure the end-expiratory pulmonary artery wedge
      pressure (PAWP) with the "expiration holding" function on the ventilator and the
      "pulmonary artery wedge pressure review" software on the monitor. MATERIALS AND
      METHODS: Fifty prospective measurements were made on 12 patients undergoing
      pulmonary artery catheter and mechanical ventilation. All measurements were
      divided into <8 mmHg or >=8 mmHg subgroups according to respiratory variability,
      and they were then subdivided into either an airway pressure display measurement
      group (AM group) or an expiration holding (EH) group for comparison. RESULTS: In
      all measurements, the two groups showed similar levels of accuracy; however, for
      the time spent for measurement, the EH group was much faster than the airway
      pressure display measurement group (P<0.001). Additionally, the EH group was
      associated with lower medical costs. CONCLUSION: The expiration holding approach
      measured the PAWP more accurately, more quickly, and with reduced costs in
      comparison to the airway pressure display approach.

PMID- 24133371
TI  - Spirituality in childhood cancer care.
AB  - To deal with the suffering caused by childhood cancer, patients and their
      families use different coping strategies, among which, spirituality appears a way
      of minimizing possible damage. In this context, the purpose of the present study
      was to analyze the influence of spirituality in childhood cancer care, involving
      biopsychosocial aspects of the child, the family, and the health care team facing
      the disease. To accomplish this purpose, a nonsystematic review of literature of
      articles on national and international electronic databases (Scientific
      Electronic Library Online [SciELO], PubMed, and Latin American and Caribbean
      Health Sciences Literature [LILACS]) was conducted using the search terms
      "spirituality," "child psychology," "child," and "cancer," as well as on other
      available resources. After the search, 20 articles met the eligibility criteria
      and were included in the final sample. Our review showed that the relation
      between spirituality and health has lately become a subject of growing interest
      among researchers, as a positive influence of spirituality in the people's
      welfare was noted. Studies that were retrieved using the mentioned search
      strategy in electronic databases, independently assessed by the authors according
      to the systematic review, showed that spirituality emerges as a driving force
      that helps pediatric patients and their families in coping with cancer. Health
      care workers have been increasingly attentive to this dimension of care. However,
      it is necessary to improve their knowledge regarding the subject. The search
      highlighted that spirituality is considered a source of comfort and hope,
      contributing to a better acceptance of his/her chronic condition by the child
      with cancer, as well as by the family. Further up-to-date studies facing the
      subject are, thus, needed. It is also necessary to better train health care
      practitioners, so as to provide humanized care to the child with cancer. 

PMID- 24133373
TI  - Clinical impact of recent genetic discoveries in osteoporosis.
AB  - Osteoporotic fracture carries an enormous public health burden in terms of
      mortality and morbidity. Current approaches to identify individuals at high risk
      for fracture are based on assessment of bone mineral density and presence of
      other osteoporosis risk factors. Bone mineral density and susceptibility to
      osteoporotic fractures are highly heritable, and over 60 loci have been robustly
      associated with one or both traits through genome-wide association studies
      carried out over the past 7 years. In this review, we discuss opportunities and
      challenges for incorporating these genetic discoveries into strategies to prevent
      osteoporotic fracture and translating new insights obtained from these
      discoveries into development of new therapeutic targets. 

PMID- 24133375
TI  - Mineralocorticoid receptor antagonists: emerging roles in cardiovascular
      medicine.
AB  - Spironolactone was first developed over 50 years ago as a potent
      mineralocorticoid receptor (MR) antagonist with undesirable side effects; it was
      followed a decade ago by eplerenone, which is less potent but much more MR
      specific. From a marginal role as a potassium-sparing diuretic, spironolactone
      was shown to be an extraordinarily effective adjunctive agent in the treatment of
      progressive heart failure, as was eplerenone in subsequent heart failure trials.
      Neither acts as an aldosterone antagonist in the heart as the cardiac MR are
      occupied by cortisol, which becomes an aldosterone mimic in conditions of tissue
      damage. The accepted term "MR antagonist", (as opposed to "aldosterone
      antagonist" or, worse, "aldosterone blocker"), should be retained, despite the
      demonstration that they act not to deny agonist access but as inverse agonists.
      The prevalence of primary aldosteronism is now recognized as accounting for about
      10% of hypertension, with recent evidence suggesting that this figure may be
      considerably higher: in over two thirds of cases of primary aldosteronism therapy
      including MR antagonists is standard of care. MR antagonists are safe and
      vasoprotective in uncomplicated essential hypertension, even in diabetics, and at
      low doses they also specifically lower blood pressure in patients with so-called
      resistant hypertension. Nowhere are more than 1% of patients with primary
      aldosteronism ever diagnosed and specifically treated. Given the higher risk
      profile in patients with primary aldosteronism than that of age, sex, and blood
      pressure matched essential hypertension, on public health grounds alone the
      guidelines for first-line treatment of all hypertension should mandate inclusion
      of a low-dose MR antagonist. 

PMID- 24133374
TI  - Phosphate control in dialysis.
AB  - Prevention and correction of hyperphosphatemia is a major goal of chronic kidney
      disease-mineral and bone disorder (CKD-MBD) management, achievable through
      avoidance of a positive phosphate balance. To this aim, optimal dialysis removal,
      careful use of phosphate binders, and dietary phosphate control are needed to
      optimize the control of phosphate balance in well-nourished patients on a
      standard three-times-a-week hemodialysis schedule. Using a mixed diffusive
      convective hemodialysis tecniques, and increasing the number and/or the duration
      of dialysis tecniques are all measures able to enhance phosphorus (P) mass
      removal through dialysis. However, dialytic removal does not equal the high P
      intake linked to the high dietary protein requirement of dialysis patients;
      hence, the use of intestinal P binders is mandatory to reduce P net intestinal
      absorption. Unfortunately, even a large dose of P binders is able to bind
      approximately 200-300 mg of P on a daily basis, so it is evident that their
      efficacy is limited in the case of an uncontrolled dietary P load. Hence,
      limitation of dietary P intake is needed to reach the goal of neutral phosphate
      balance in dialysis, coupled to an adequate protein intake. To this aim, patients
      should be informed and educated to avoid foods that are naturally rich in
      phosphate and also processed food with P-containing preservatives. In addition,
      patients should preferentially choose food with a low P-to-protein ratio. For
      example, patients could choose egg white or protein from a vegetable source.
      Finally, boiling should be the preferred cooking procedure, because it induces
      food demineralization, including phosphate loss. The integrated approach outlined
      in this article should be actively adapted as a therapeutic alliance by
      clinicians, dieticians, and patients for an effective control of phosphate
      balance in dialysis patients. 

PMID- 24133376
TI  - Prospective study evaluating the radiosensitizing effect of reduced doses of
      temozolomide in the treatment of Egyptian patients with glioblastoma multiforme.
AB  - PURPOSE: In view of the documented toxicity of continuous daily radiosensitizer
      doses of temozolomide concomitant with radiation in the treatment of glioblastoma
      multiforme, we aimed to compare it with a different schedule of abbreviated
      radiosensitizer dosing. PATIENTS AND METHODS: This was a randomized prospective
      study comparing toxicity and survival in 60 Egyptian patients with glioblastoma
      multiforme. Patients in arm I received temozolomide at a dose of 75 mg/m(2) daily
      with radiotherapy for 42 days, starting 4 weeks after surgery and reaching to a
      total radiation dose of 60 Gy/30 Fractions/6 weeks, while patients in arm II
      received temozolomide at a dose of 75 mg/m(2) concomitantly with the same
      radiotherapy schedule daily in the first and last weeks of the same radiotherapy
      program. RESULTS: Common grade 1-2 adverse events were malaise in 28 patients
      (46.7%), followed by alopecia (40%) and nausea (26.7%). Grade 3-4 convulsion and
      decreased level of consciousness was seen in only four patients who were all from
      arm I. The median progression-free survival (PFS) for the entire study population
      was 10.6 months (95% confidence interval [CI] 7.3-14), and PFS at 12 months was
      32%. The median PFS in arm I was 8.8 months (95% CI 5.9-11.7) and in arm II 11.5
      months (95% CI 8.9-14.2), and PFS at 12 months for both arms was 32% and 30%
      respectively (P=0.571). The median overall survival (OS) of the whole group of
      patients was 14.2 months (95% CI 13-15.5), and OS was 70% at 12 months and 25% at
      18 months. The median OS for patients in arm I was 12.3 months (95% CI 7.7-16.9),
      whereas in arm II it was 14.3 months (95% CI 14-14.7) (P=0.83). CONCLUSION:
      Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in
      glioblastoma multiforme exhibited comparable efficacy with a classic continuous
      daily schedule, though with better tolerability.

PMID- 24133372
TI  - The emerging and diverse roles of sirtuins in cancer: a clinical perspective.
AB  - Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide
      (NAD(+))-dependent protein lysine modifying enzymes with deacetylase, adenosine
      diphosphateribosyltransferase and other deacylase activities. Mammals have seven
      sirtuins, namely SIRT1-7. They are key regulators for a wide variety of cellular
      and physiological processes such as cell proliferation, differentiation, DNA
      damage and stress response, genome stability, cell survival, metabolism, energy
      homeostasis, organ development, aging, and cancer. Here we present an extensive
      literature review of the roles of mammalian sirtuins, particularly SIRT1 as that
      is the most studied sirtuin, in human epithelial, neuronal, hematopoietic, and
      mesenchymal malignancies, covering breast, prostate, lung, thyroid, liver, colon,
      gastric, pancreatic, ovarian, and cervical cancers, tumors of the central nervous
      system, leukemia and lymphoma, and soft tissue sarcomas. Collective evidence
      suggests sirtuins are involved in both promoting and suppressing tumorigenesis
      depending on cellular and molecular contexts. We discuss the potential use of
      sirtuin modulators, especially sirtuin inhibitors, in cancer treatment. 

PMID- 24133377
TI  - Translation and validation of the Western Ontario Osteoarthritis of the Shoulder
      (WOOS) index - the Danish version.
AB  - BACKGROUND AND PURPOSE: The Western Ontario Osteoarthritis of the Shoulder (WOOS)
      index is a patient-reported, disease-specific questionnaire for the measurement
      of the quality-of-life in patients with osteoarthritis. The purpose of this study
      was to describe the process used to translate the WOOS into Danish and to test
      the translation in a Danish population, in terms of validity, reliability, and
      responsiveness. MATERIAL AND METHODS: The translation of the WOOS was done
      according to international standardized guidelines. The psychometric properties
      were tested in 20 consecutive patients. The eligibility criteria were: a
      diagnosis of osteoarthritis without symptomatic rotator cuff pathology and
      treated with primary shoulder replacement. Patients were excluded only in the
      case of other pathology of the upper extremity or in the case of cognitive or
      linguistic impairment compromising the ability to complete the questionnaires.
      RESULTS: The Pearson's correlation coefficient between the WOOS and the Constant
      Murley score (CMS), preoperatively was 0.62 (P = 0.004) and the correlation
      between the changes of score for the WOOS and CMS was 0.73 (P < 0.001). The
      correlation coefficient between the WOOS and the CMS, SF-36, and the Oxford
      Shoulder Score postoperatively was 0.82 (P < 0.001), 0.48 (P = 0.03), and 0.82 (P
      < 0.001), respectively. There were no floor and ceiling effects. The Cronbach's
      alpha was 0.98. The intraclass correlation coefficient between test and retest
      was 0.96. The standardized response mean was 1.41, and effect size was 2.32.
      CONCLUSION: We have shown that the Danish version of the WOOS, translated
      according to international standardized guidelines, has substantial statistical
      and clinical psychometric properties at the same level as was described for the
      original version.

PMID- 24133378
TI  - Impact of psychoeducation on professional stress reduction among prison guards.
AB  - CONFLICT OF INTEREST: NONE DECLARED. INTRODUCTION: Through psychological support
      for prison guard's awareness about professional stress and burn-out, cognitive
      assessment of stress consequences, insight in coping strategies, as well as
      prevention of stress consequences is achieved. AIM: Evaluation of psychoeducation
      effects on professional stress consequences within prison guards. METHOD: In the
      research were included 122 prison guards from three prisons in Bosnia and
      Herzegovina. All of them have been tested before and after psychoeducation was
      finished using following instruments: Index of reaction, STAI questionnaire,
      SAMACA questionnaire. RESULTS: Differences between first and second measuring of
      subjects included in this study in Sarajevo prison indicated statistically
      significant reduction of stress reactions, improvement of coping strategies and
      communication skills. In prisons Zenica and Kula there are differences between
      first and second measurement in stress reactions reduction, improvement of coping
      strategies and overcoming of stress and improvement of communication skills as
      well, which are not statistically significant. In Kula prison, significant
      differences between two measurements in attitudes of prison guards toward
      detainees were observed. CONCLUSIONS: Results of this study show that prison
      guards within prisons where are detained persons with long period of imprisonment
      are more exposed to professional stress, comparing to prison guards who are
      employed in investigation prison. Psychoeducation resulted in positive effects
      and it should be obligatory included in prison guards training with the aim of
      decreasing of psychological consequences of prolonged professional stress to
      which they are exposed to. Psychoeducation should be on continuous basis and led
      by educated mental health professionals.

PMID- 24133379
TI  - Dental office waste - public health and ecological risk.
AB  - CONFLICT OF INTEREST: NONE DECLARED Waste management is one of the key ecological
      challenges of the modern world. As dental practitioners, we must recognize that
      some of the materials and procedures we use to provide dental health services may
      present challenges to the environment. Realizing this, we can begin to take
      measures to minimize the production of these wastes and their potential
      environmental effects. Dental office waste typically cause toxic chemicals to
      enter our streams, sewers, and landfills. This paper identifies some common
      wastes produced by dental offices (dental amalgam, silver, lead, biomedical and
      general office waste) and provides practical suggestions for reducing the impact
      of our profession on the environment. To dispose of dental wastes, if recycling
      is not an option, proper disposal as hazardous waste is necessary. But, problem
      is that dental waste is in most cases dumped at uncontrolled disposal sites, and
      that is public health and ecological risk.

PMID- 24133380
TI  - How to rationally use information diagnostic technologies in family and general
      medicine practice.
AB  - CONFLICT OF INTEREST: NONE DECLARED New discoveries in technology indeed enabled
      significant improvement of health care in the last three decades. Only during the
      last few years a significant breakthrough is achieved in the field of antiviral
      drugs, biotechnology, digital diagnostic technology, molecular diagnosis, tissues
      and organs transplantation as well as surgical and information technologies,
      which all contributed to the improvement of health care. Rapid growth of medical
      technology has led to the increase in costs of health care, increased access to
      these technologies and improvement of health care that is permanently encouraging
      the further development of technology. Technology encompasses the skills,
      knowledge and ability to understand, use and create useful things. It is the
      practical application of knowledge. Evaluation of health technology is the
      systematic evaluation of characteristics, results or impact of health
      technologies. The primary purpose of evaluation is to provide information to
      responsible parties for the technology in the health care system, which will be
      used in decision-making and introduction of these technologies. Information
      technology in medicine and health care represents all medical and health
      technology in the process of work, monitoring and evaluation done using computer
      technology. Progress of medical science in recent years especially needs to thank
      to the development of information technologies. The health care system of Bosnia
      and Herzegovina is currently operating in the two sub-systems of primary health
      care. One is inherited from the past system, in which the primary health care is
      provided by general practitioners, specialists in general practice, as well as
      gynecologists, pediatricians and pulmologists, and the second subsystem occurs
      when in PHC is introduced the system of family medicine doctors and family
      medicine specialists. Family medicine, based on the concept of orientation
      towards the methods which are more effective, rational and cost-effective health
      care, use of defined procedures and evidence-based medicine, and more adequate
      education can empower and stimulate general practice doctors, especially family
      medicine specialists, who have passed various forms of training and courses in
      this area, to more rational and efficient use of diagnostic technology in their
      daily practice, without unnecessary duplication of tests. With this they make
      savings to the healthcare system, improve the financial position of overall
      health system, especially in the PHC segment, increase satisfaction of doctors
      providing that health care, but also the users of health services.

PMID- 24133381
TI  - Quality assessment of family medicine teams based on accreditation standards.
AB  - CONFLICT OF INTEREST: NONE DECLARED In order to speed up and simplify the self
      assessment and external assessment process, provide better overview and access to
      Accreditation Standards for Family Medicine Teams and better assessment documents
      archiving, Agency for Healthcare Quality and Accreditation in Federation of
      Bosnia and Herzegovina (AKAZ) has developed self assessment and externals
      assessment software for family medicine teams. This article presents the
      development of standardized software for self and external evaluation of quality
      of service in family medicine, as well as plans for the future development of
      this software package.

PMID- 24133382
TI  - The jubilee of medical informatics in bosnia and herzegovina - 20 years
      anniversary.
AB  - CONFLICT OF INTEREST: NONE DECLARED LAST TWO YEARS, THE HEALTH INFORMATICS
      PROFESSION CELEBRATED FIVE JUBILEES IN BOSNIA AND HERZEGOVINA: thirty years from
      the introduction of the first automatic manipulation of data, twenty years from
      the establishment of Society for Medical Informatics BiH, fifteen years from the
      establishment of the Scientific and Professional Journal of the Society for
      Medical Informatics of Bosnia and Herzegovina "Acta Informatica Medica", fifteen
      years on from the establishment of the first Cathedra for Medical Informatics on
      Biomedical Faculties in Bosnia and Herzegovina and five years on from the
      introduction of the method of "Distance learning" in medical curriculum. The
      author of this article are eager to mark the importance of the above mentioned
      Anniversaries in the development of Health informatics in Bosnia and Herzegovina
      and have attempted, very briefly, to present the most significant events and
      persons with essential roles throughout this period.

PMID- 24133383
TI  - The role of extracellular vesicles in phenotypic cancer transformation.
AB  - BACKGROUND: Cancer has traditionally been considered as a disease resulting from
      gene mutations. New findings in biology are challenging gene-centered
      explanations of cancer progression and redirecting them to the non-genetic
      origins of tumorigenicity. It has become clear that intercellular communication
      plays a crucial role in cancer progression. Among the most intriguing ways of
      intercellular communication is that via extracellular vesicles (EVs). EVs are
      membrane structures released from various types of cells. After separation from
      the mother membrane, EVs become mobile and may travel from the extracellular
      space to blood and other body fluids. CONCLUSIONS: Recently it has been shown
      that tumour cells are particularly prone to vesiculation and that tumour-derived
      EVs can carry proteins, lipids and nucleic acids causative of cancer progression.
      The uptake of tumour-derived EVs by noncancerous cells can change their normal
      phenotype to cancerous. The suppression of vesiculation could slow down tumour
      growth and the spread of metastases. The purpose of this review is to highlight
      examples of EV-mediated cancer phenotypic transformation in the light of possible
      therapeutic applications.

PMID- 24133385
TI  - Prediction of 2 years-survival in patients with stage I and II non-small cell
      lung cancer utilizing (18)F-FDG PET/CT SUV quantification.
AB  - BACKGROUND: The purpose of the study was to evaluate the correlation between the
      maximum standardized uptake value (SUVmax), size of primary lung lesion, disease
      free survival (DFS) and overall survival (OS) in patients with stage I and II non
      small cell lung cancer (NSCLC) in 2 years follow-up. PATIENTS AND METHODS: Forty
      nine patients with stage I-II NSCLC were included in this study. Pre-surgical 2
      deoxy-2-[18F]fluoro-D-glucose positron-emission tomography ((18)F-FDG PET/CT)
      study was performed for all patients. The relationship between SUVmax, tumour
      size and clinical outcome was measured. The cut-off value for SUVmax and tumour
      size with the best prognostic significance, probability of DFS and the
      correlation between SUVmax and the response to therapy were calculated. RESULTS:
      There was a statistically significant correlation between SUVmax and DFS (p =
      0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for
      tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30
      mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was
      <30 mm and/or SUVmax was <9. CONCLUSIONS: In stage I-II, SUVmax and tumour size
      might be helpful to identify the subgroup of patients with high chance for
      recurrence.

PMID- 24133384
TI  - Comparison between whole-body MRI and Fluorine-18-Fluorodeoxyglucose PET or
      PET/CT in oncology: a systematic review.
AB  - BACKGROUND: The aim of the article is to systematically review published data
      about the comparison between positron emission tomography (PET) or PET/computed
      tomography (PET/CT) using Fluorine-18-Fluorodeoxyglucose (FDG) and whole-body
      magnetic resonance imaging (WB-MRI) in patients with different tumours. METHODS:
      A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus
      and Embase databases through April 2012 and regarding the comparison between FDG
      PET or PET/CT and WB-MRI in patients with various tumours was carried out.
      RESULTS: Forty-four articles comprising 2287 patients were retrieved in full-text
      version, included and discussed in this systematic review. Several articles
      evaluated mixed tumours with both diagnostic methods. Concerning the specific
      tumour types, more evidence exists for lymphomas, bone tumours, head and neck
      tumours and lung tumours, whereas there is less evidence for other tumour types.
      CONCLUSIONS: Overall, based on the literature findings, WB-MRI seems to be a
      valid alternative method compared to PET/CT in oncology. Further larger
      prospective studies and in particular cost-effectiveness analysis comparing these
      two whole-body imaging techniques are needed to better assess the role of WB-MRI
      compared to FDG-PET or PET/CT in specific tumour types.

PMID- 24133386
TI  - Advanced ultrasonography technologies to assess the effects of radiofrequency
      ablation on hepatocellular carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a curative therapy for
      hepatocellular carcinoma (HCC). In RFA, ultrasonography (US) is most commonly
      used to guide tumor puncture, while its effects are assessed using dynamic
      computed tomography or magnetic resonance. The differences in modalities used for
      RFA and assessment of its effects complicate RFA. We developed a method for
      assessing the effects of RFA on HCC by combining contrast-enhanced (CE) US and
      real-time virtual sonography with three-dimensional US data. PATIENTS AND
      METHODS: Before RFA, we performed a sweep scan of the target HCC nodule and the
      surrounding hepatic parenchyma to generate three-dimensional US data. After RFA,
      we synchronized multi-planar reconstruction images derived from stored three
      dimensional US data with real-time US images on the same US monitor and performed
      CEUS and real-time virtual sonography. Using a marking function, we drew a sphere
      marker along the target HCC nodule contour on pre-treatment US- multi-planar
      reconstruction images so that the automatically synchronized sphere marker
      represented the original HCC nodule contour on post-treatment real-time CEUS
      images. Ablation was considered sufficient when an avascular area with a margin
      of several millimeters in all directions surrounded the sphere marker on CEUS.
      RESULTS: This method was feasible and useful for assessing therapeutic effects in
      13 consecutive patients with HCC who underwent RFA. In 2 patients who underwent
      multiple sessions of RFA, HCC-nodule portions requiring additional RFA were
      easily identified on US images. CONCLUSIONS: This method using advanced US
      technologies will facilitate assessment of the effects of RFA on HCC.

PMID- 24133387
TI  - Intrathoracic malignant peripheral nerve sheath tumors: imaging features and
      implications for management.
AB  - BACKGROUND: The aim of the study was to analyze the clinical and imaging
      characteristics of primary intrathoracic malignant peripheral nerve sheath tumors
      (MPNSTs). PATIENTS AND METHODS: In this institutional review board (IRB)-approved
      retrospective study, clinical and imaging features of 15 patients (eight men;
      mean age 50 years [range 18-83)] with pathologically proven malignant peripheral
      nerve sheath tumors seen from January 1999 to December 2011 were analyzed.
      Imaging features (CT in 15, MRI in 5 and PET/CT in 4) of primary tumors were
      evaluated by three radiologists and correlated with clinical management. RESULTS:
      Of the 15 tumors, six were located in the mediastinum (two each in anterior,
      middle and posterior mediastinum), four in chest wall, two were paraspinal, and
      three in the lung. Four patients had neurofibromatosis-1 (NF1); four tumors had
      heterologous rhabdomyoblastic differentiation (malignant triton tumor). Masses
      typically were elongated along the direction of nerves, with mean size of 11 cm.
      The masses were hypo- or isodense to muscles on CT, isointense on T1-weighted
      images, hyperintense on T2-weighted images and intensely fluorodeoxyglucose (FDG)
      avid (mean standardized uptake value [SUV]max of 10.5 [range 4.4-23.6]). Necrosis
      and calcification was seen in four tumors each. Finding of invasion of adjacent
      structures on imaging led to change in management in seven patients; patients
      with invasion received chemoradiation. CONCLUSIONS: Intrathoracic MPNSTs appear
      as large elongated masses involving mediastinum, lung or chest wall. Radiological
      identification of invasion of adjacent structures is crucial and alters therapy,
      with patients with invasion receiving neoadjuvant or adjuvant chemoradiation.

PMID- 24133388
TI  - Percutaneous mechanical thrombectomy of superior mesenteric artery embolism.
AB  - BACKGROUND: The present series present three consecutive cases of successful
      percutaneous mechanical embolectomy in acute superior mesenteric artery ischemia.
      Superior mesenteric artery embolism is a rare abdominal emergency that commonly
      leads to bowel infarction and has a very high mortality rate. Prompt recognition
      and treatment are crucial for successful outcome. Endovascular therapeutic
      approach in patients with acute SMA embolism in median portion of its stem is
      proposed. CASE REPORTS: Three male patients had experienced a sudden abdominal
      pain and acute superior mesenteric artery embolism in median portion of its stem
      was revealed on computed tomography angiography. No signs of intestinal
      infarction were present. The decision for endovascular treatment was made in
      concordance with the surgeons. In one patient 6 French gauge Rotarex((r)) device
      was used while in others 6 French gauge Aspirex((r)) device were used. All
      patients experienced sudden relief of pain after the procedure with no signs of
      intestinal infarction. Minor procedural complication - rupture of a smaller
      branch of SMA during Aspirex((r)) treatment was successfully managed by coiling
      while transient paralytic ileus presented in one patient resolved spontaneously.
      All three patients remained symptom-free with patent superior mesenteric artery
      during the follow-up period. CONCLUSIONS: Percutaneous mechanical thrombectomy
      seems to be a rapid and effective treatment of acute superior mesenteric artery
      embolism in median portion of its stem in absence of bowel necrosis. Follow-up of
      our patients showed excellent short- and long-term results.

PMID- 24133389
TI  - Magnetic resonance imaging of vulvar dermatofibrosarcoma protuberans - report of
      a case.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) of the vulva is a rare low
      grade soft tissue sarcoma. Magnetic resonance imaging (MRI) findings of vulvar
      DFSP were essentially unreported in the literature. CASE REPORT: We report a DFSP
      of vulva with its clinical, histological and MRI features. As far we know this is
      the first case of histologically confirmed vulvar DFSP presenting with MR images.
      The diagnosis of DFSP is usually made by histopathologic and clinical findings.
      CONCLUSIONS: MRI is useful both for the diagnosis of DFSP and following up the
      patients since it has high soft tissue resolution and no risk of radiation
      exposure. With MRI the relation to the adjacent anatomical structures, extension
      and depth of the tumour and possible lymph node involvement can also be
      demonstrated.

PMID- 24133390
TI  - The potential value of the neutral comet assay and gammaH2AX foci assay in
      assessing the radiosensitivity of carbon beam in human tumor cell lines.
AB  - BACKGROUND: Carbon ions ((12)C(6+)) are high linear energy transfer (LET)
      radiation characterized by higher relative biological effectiveness than low LET
      radiation. The assessment of tumour radiosensitivity would be particularly useful
      in optimizing the radiation dose during radiotherapy. The aim of the current
      study was to evaluate the potential value of the neutral comet assay and
      gammaH2AX foci assay in assessing (12)C(6+) radiosensitivity of tumour cells.
      MATERIALS AND METHODS: The doses of (12)C(6+) and X-rays used in the present
      study were 2 and 4 Gy. The survival fraction, DNA double-strand breaks (DSB) and
      repair kinetics of DSB were assayed with clonogenic survival, neutral comet assay
      and gammaH2AX foci assay in human cervical carcinoma HeLa cells, hepatoma HepG2
      cells, and mucoepidermoid carcinoma MEC-1 cells at the time points of 0.5, 4, 16
      and 24 h after (12)C(6+) and X-rays irradiation. RESULTS: The survival fraction
      for 12C6+ irradiation was much more inhibited than for X-rays (p < 0.05) in all
      three tumour cell lines tested. Substantial amounts of residual damage, assessed
      by the neutral comet assay, were present after irradiation (p < 0.05). The
      highest residual damage was observed at 0.5 or 4 h, both for (12)C(6+) and X-ray
      irradiation. However, the residual damage in HeLa and MEC-1 cells was higher for
      (12)C(6+) than X-rays (p < 0.05). The strongest induction of gammaH2AX foci was
      observed after 30 min, for all three tumour cell lines (p < 0.01). The franction
      of gammaH2AX foci persisted for at least 24 h after (12)C6+ irradiation; in HeLa
      cells and MEC-1 was higher than after X-ray irradiation (p < 0.05). The
      correlation coefficients between the clonogenic survival, neutral comet assay and
      gammaH2AX foci assay were not statistically significant, except for some tumour
      cells at individual irradiation doses and types. CONCLUSIONS: Our study
      demonstrated that the neutral comet assay and gamma-H2AX foci assay could be used
      to assess the radiosensitivity of (12)C(6+) in human tumour cells.

PMID- 24133391
TI  - Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells
      and dendritic cells infected with Helicobacter pylori.
AB  - BACKGROUND: The immune response to Helicobacter pylori importantly determines the
      outcome of infection as well as the success of eradication therapy. We
      demonstrate the role of a cysteine protease cathepsin X in the immune response to
      H. pylori infection. MATERIALS AND METHODS: We analysed how the inhibition of
      cathepsin X influenced the immune response in experiments when THP-1 cells or
      dendritic cells isolated from patients were stimulated with 48 strains of H.
      pylori isolated from gastric biopsy samples of patients which had problems with
      the eradication of bacteria. RESULTS: The experiments, performed with the help of
      a flow cytometer, showed that the expression of Toll-like receptors (TLRs),
      especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells
      was higher when we stimulated cells with H. pylori together with inhibitor of
      cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H.
      pylori only, and also in comparison with negative control samples. We also
      demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the
      concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were
      stimulated with H. pylori only. CONCLUSIONS: We demonstrated that inhibition of
      cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4
      redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is
      blocked. The beginning of a successful immune response against H. pylori in the
      case of inhibition of cathepsin X is delayed.

PMID- 24133392
TI  - Early outcome in endoscopic extended endonasal approach for removal of
      supradiaphragmatic craniopharyngiomas: a case series and a comprehensive review.
AB  - BACKGROUND: The choice of endoscopic expanded endonasal approach introduces the
      possibility of improved gross total resection of craniopharyngioma while
      minimizing surgical morbidity in a significant subset of patients. METHODS: From
      our trans-sphenoidal surgical series of 331 cases, we retrospectively reviewed
      visual, endocrine and neuro-cognitive outcomes in the first consecutive eight
      patients (median age 63 years; range 47-73 years) with newly diagnosed
      supradiaphragmatic craniopharyngioma (median tumour height 23 mm; range 15-34
      mm), removed by expanded endonasal approach (median follow-up 27 months; range 10
      69 months). Gross total resection was attempted in all patients. RESULTS: Gross
      total resection was achieved in 6 of 8 patients. Visual improvement was present
      in 6 of 8 patients of patients or in 14 of 16 eyes. New endocrinopathy, including
      diabetes insipidus, appeared in 5 of 8 patients. Stalk was preserved in 4
      patients. Cognitive decline was present in 2 cases. Five of 8 patients retained
      previous quality of life. CONCLUSIONS: Our early outcome results are comparable
      to the recent few expanded endonasal approach series, except for the incidence of
      new endocrinopathy and cerebrospinal fluid leak rate. This was influenced by
      higher number of transinfundibular tumours in our series, where stalk
      preservation is less likely, and not using nasoseptal flap or gasket closure in
      the first half of cases. Including data from the literature and ours, expanded
      endonasal approach shows a trend for improved gross total resection rate with
      less morbidity, more obviously for visual outcome and quality of life than for
      endocrine outcome. However, validity of expanded endonasal approach should be
      confirmed in a larger number of patients with a longer follow-up period.

PMID- 24133393
TI  - Definitive radiotherapy for uterine cervix cancer: long term results for patients
      treated in the period from 1998 till 2002 at the Institute of Oncology Ljubljana.
AB  - BACKGROUND: The aim of this retrospective study was to analyse results of the two
      dimensional (2D) uterine cervix cancer treatment at the Institute of Oncology
      Ljubljana from 1998 till 2002, before the three-dimensional (3D) approach was
      introduced in our clinical practice. METHODS: Ninety-eight patients with the
      following FIGO stage distribution were analysed: 10% IB, 7% IIA, 37% IIB, 4% IIIA
      and 42% IIIB. The influence of age, haemoglobin level, histology, grade, stage,
      lymph node status, cumulative point A dose, and an overall treatment time on the
      survival and local control (LC) were evaluated. Acute and late side effects were
      assessed. RESULTS: Five and 8-year overall survival (OS), disease specific
      survival (DSS) and LC rate were as follows: 47.2% and 43.0%, 54.7% and 53.4%,
      74.9% and 72.5%, respectively. Point A dose and histology of the tumour
      influenced OS, positive lymph nodes DSS and point A dose LC rate. Probability of
      grade three and four late complications in the first five years was 7.1% for
      gastrointestinal tract and 3.3% for genitourinary system and vagina. CONCLUSIONS:
      Point A dose was independent predictor of OS and LC rate, lymph node status
      predicted DSS, while histology of the tumour influenced OS.

PMID- 24133394
TI  - Evaluation of safety and analgesic consumption in patients with advanced cancer
      treated with zoledronic acid.
AB  - BACKGROUND: The aim of the study was evaluation of zoledronic acid with regard to
      safety, effect on analgesic consumption and impact on occurrence of skeletal
      related events in patients with bone lesions from solid tumors and multiple
      myeloma. METHODS: We conducted an observational, 12-month, phase IV and multi
      center study. One hundred and twenty-five symptomatic (pain) bone-metastatic
      patients were included between 2007 and 2009: 92 prostate cancers, 28 multiple
      myelomas, 5 others. They were prescribed monthly infusions of zoledronic acid in
      accordance to each disease's treatment guidelines. Analgesics consumption, pain
      and laboratory values were evaluated. RESULTS: Zoledronic acid was prescribed
      concurrent to initial therapy for myeloma and only in late stage of prostate
      cancer. With treatment, percentage of patients on analgesics decreased in myeloma
      group (from 57% to 24%) and increased in prostate cancer group (from 70% to 88%).
      In patients with any analgesics, the use of opiates' prescription dropped from
      72.9% to 64%, percentages of non-steroidal analgesics and other mild analgesics
      increased slightly. Pain score (Visual Analog Scale, VAS) decreased non
      significantly (by 22%) in prostate cancer but significantly in myeloma (by 97%).
      Hypocalcaemia grade 3 or 4 was observed in 4% of patients. Deviations in
      creatinine remained stable throughout. A total of 31 skeletal related events were
      reported for 10 patients (8%). CONCLUSIONS: Zoledronic acid was safe medication.
      Different response of pain was seen between prostate cancer and myeloma patients,
      which might be due to different stages of disease where it was prescribed
      according to present guidelines. Possibility of earlier start of treatment should
      be explored in prostate cancer.

PMID- 24133395
TI  - Usability application of multiplex polymerase chain reaction in the diagnosis of
      microorganisms isolated from urine of patients treated in cancer hospital.
AB  - BACKGROUND: THE OBJECTIVE OF THIS STUDY WAS: i) to compare the results of urine
      culture with polymerase chain reaction (PCR) -based detection of microorganisms
      using two commercially available kits, ii) to assess antimicrobial susceptibility
      of urine isolates from cancer patients to chosen antimicrobial drugs and, if
      necessary, to update the recommendation of empirical therapy. MATERIALS AND
      METHODS: A one-year hospital-based prospective study has been conducted in
      Greater Poland Cancer Centre and Genetic Medicine Laboratory CBDNA Research
      Centre in 2011. Urine cultures and urine PCR assay from 72 patients were
      examined. RESULTS: Urine cultures and urine PCR assay from 72 patients were
      examined. Urine samples were positive for 128 strains from which 95 (74%) were
      identical in both tests. The most frequently isolated bacteria in both culture
      and PCR assay were coliform organisms and Enterococcus spp. The Gram negative
      bacilli were most resistant to cotrimoxazol. 77.2% of these bacilli and 100% of
      E. faecalis and S. agalactiae were sensitive to amoxicillin-clavulanic acid. 4.7%
      of Gram positive cocci were resistant to nitrofurantoin. CONCLUSIONS: The PCR
      method quickly finds the causative agent of urinary tract infection (UTI) and,
      therefore, it can help with making the choice of the proper antimicrobial therapy
      at an early stage. It appears to be a viable alternative to the recommendations
      made in general treatment guidelines, in cases where diversified sensitivity
      patterns of microorganisms have been found.

PMID- 24133396
TI  - Estimated collective effective dose to the population from nuclear medicine
      examinations in Slovenia.
AB  - BACKGROUND: A national survey of patient exposure from nuclear medicine
      diagnostic procedures was performed by Slovenian Radiation Protection
      Administration in order to estimate their contribution to the collective
      effective dose to the population of Slovenia. METHODS: A set of 36 examinations
      with the highest contributions to the collective effective dose was identified.
      Data about frequencies and average administered activities of radioisotopes used
      for those examinations were collected from all nuclear medicine departments in
      Slovenia. A collective effective dose to the population and an effective dose per
      capita were estimated from the collected data using dose conversion factors.
      RESULTS: The total collective effective dose to the population from nuclear
      medicine diagnostic procedures in 2011 was estimated to 102 manSv, giving an
      effective dose per capita of 0.05 mSv. CONCLUSIONS: The comparison of results of
      this study with studies performed in other countries indicates that the nuclear
      medicine providers in Slovenia are well aware of the importance of patient
      protection measures and of optimisation of procedures.

PMID- 24133397
TI  - Epidemiology of major burns at the Lebanese Burn Center in Geitawi, Lebanon.
AB  - Burn care is one of the few areas in medicine considered both medically and
      surgically challenging, with burn injuries affecting people of all ages and both
      sexes. Between May 1992 and March 2012, 1,524 patients were admitted to the
      Lebanese Burn Center in Geitawi, with an average length of stay (LOS) of 36.5
      days. The most frequently encountered injuries were thermal burns, generally
      resulting from domestic accidents. Of our patients, 47% were from rural areas and
      burned body surface (BBS) was the most serious factor, with 36% of all those
      admitted having suffered burns of 20% to 40% of their total body surface area
      (TBSA). Our team of experienced physicians, nurses, nutritionists and physical
      therapists was essential to successful burn care and outcomes were improved with
      adequate early fluid intake. The main causes of death were multiple organ failure
      due to hemodynamic instability, followed by respiratory failure from inhalation
      injury. A week after the injury, risk of infection was the main threat to the
      burn victims. Although this threat was compounded by malnutrition and
      immunodeficiency, excessive use of antibiotics was not justified. The fatality
      rate was about 18% and correlates with higher TBSA burns. 

PMID- 24133398
TI  - Post-burn pruritus: need for standardization of care in Nigeria.
AB  - It is generally agreed among burn care specialists that pruritus (itching) is a
      very common and distressing complication of burn injuries that results in extreme
      discomfort. There is no consensus on treatment modality worldwide but there are
      generally accepted methods of managing amelioration. This survey aims to study
      the knowledge, attitudes and practices of Nigerian burn specialists who manage
      various degrees of burn injuries in our environment. The purpose is to find out
      whether there are any uniform modalities of care for these patients, with the
      view of possibly providing standardization. To this end, a structured
      questionnaire was designed and distributed to plastic surgeons from across
      Nigeria. Findings showed that 88.6% of the plastic surgeons had no form of
      assessment tool or method for evaluating post-burn pruritus, leaving only 11.4%
      believing they had a method of assessing the severity of post-burn pruritus. With
      regard to treatment, 57.1% would use oral medications as first-line treatment,
      22.9% would use injectables, 8.6% would use topical agents, 5.7% would only
      reassure the patients and another 5.7% would use a combination of oral and
      topical agents together. 85.7% of these plastic surgeons and burn care
      specialists did not have any form of anti-pruritic regimen, as only 14.3%
      indicated having this. Hence, there is no standardization in the management of
      pruritus in Nigeria and there is an urgent need for a management protocol. 

PMID- 24133399
TI  - Possible risk factors associated with burn wound colonization in burn units of
      Gaza strip hospitals, Palestine.
AB  - The epidemiological pattern and risk factors of burns and burn infections varies
      widely in different parts of the world. This study aims to determine the
      epidemiologic pattern of burn injuries and possible risk factors associated with
      burn infections in burn units of Gaza strip hospitals. A total of 118 patients
      were included in the study. The data collected included: patient age and gender,
      the causes, site, degree, and TBSA of the burns, as well as surgical operations,
      length of hospital stay, and microbiological profile of samples collected from
      patients, the environment, and from health care staff. Pediatric and adult
      patients accounted for 72% and 28% respectively. 58.5% of all patients were male
      and 41.5% were female. The most common etiological factors in children were
      scalding, while in adults these were open fire and flammable liquids. The mean
      TBSA was 12% with a range from 1-90%. Second and third degree burns accounted for
      78% and 22% respectively. The area of the body most often affected was the torso
      (39%), followed by the lower limb (29.7%), and upper limb (17.8%). The
      predominant microorganisms isolated from burn wounds were Pseudomonas aeruginosa,
      Enterobacter spp. and Staphylococcus spp. The study showed the highest risk
      groups to be children and males, and enabled us to identify possible risk factors
      that can help in future efforts toward prevention and minimizing nosocomial
      infections in burn units of Gaza strip hospitals. 

PMID- 24133400
TI  - Distribution of genes encoding tetracycline resistance and aminoglycoside
      modifying enzymes in Staphylococcus aureus strains isolated from a burn center.
AB  - Staphylococcus aureus (S. aureus) is one of the most common organisms associated
      with infections among burn patients and has shown a frequent and rapid
      development of antibiotic resistance. The presence of genes encoding
      aminoglycoside modifying enzymes (AME) and tetracycline resistance were detected
      by PCR and multiplex-PCR. Among the 151 S. aureus isolates recovered from the
      burn patients, 96 (63.6%) were detected to have mecA gene. The rate of
      tetracycline resistance genes associated with mecA was 61% (92/151). Forty nine
      isolates (32.4%) contained tetM, 26 (17.2%) possessed only tetK and 21 (13.9%)
      contained both tetM and tetK. The presence of the aac(6')-Ie-aph(2'')-I gene was
      determined in 18 isolates, aph(3')-IIIa in 8 isolates, both the aac(6')-Ie
      aph(2'')-I, aph(3')-IIIa and the ant(4')-Ia genes in 69 isolates, both aac(6')-Ie
      aph(2'')-I and ant(4')-Ia in 6 isolates, and both the aph(3')-IIIa and the
      ant(4')-Ia genes in 8 isolates. Most of the strains which harboured the mecA gene
      also contained the tet and AME genes. 

PMID- 24133402
TI  - Hypoglossal nerve paralysis in a burn patient following mechanical ventilation.
AB  - Traumatic injury resulting in isolated dysfunction of the hypoglossal nerve is
      relatively rare and described in few case reports. We present a patient with
      isolated unilateral palsy of the twelfth cranial nerve (CN XII) resulting from
      recurrent airway intervention following extensive burn injuries. The differential
      diagnosis for paralysis of the CN XII is also discussed herein. This case
      illustrates the significance of comprehensive diagnostic evaluation and the need
      for refined airway manipulation in patients that require multiple endotracheal
      intubations. 

PMID- 24133401
TI  - [Not Available].
AB  - Infectious complications of finger-joints in association with hand burns are
      common and dominated by osteoarthritis. However, this issue has hardly ever been
      addressed in the literature. This ailment can either be identified while patients
      with extensive burns are undergoing intensive care, or during patient
      rehabilitation. In the former instance, it is difficult to recognize because
      patient sedation means the clinical signs are not obvious. In the latter phase,
      however, the pain, swelling (tumefaction), stiffness and radiological signs are
      clear. These infections should be diagnosed as soon as possible in order to
      preserve the function of the hand. 

PMID- 24133403
TI  - Combined use of negative pressure wound therapy and Integra(r) to treat complex
      defects in lower extremities after burns.
AB  - Deep and extensive burns of lower extremities present a difficult challenge to
      healthcare professionals. After debridement, bones, tendons or joints are
      frequently exposed and cannot be covered by simple autografts. Moreover, in the
      case of major burns, damage to the surrounding areas of skin and the severity of
      the patient's overall condition, often count against using pedicled or
      microsurgical flaps. In dealing with such complex wounds, which are difficult to
      treat, several authors have recommended the combined use of Integra((r)) and
      negative pressure wound therapy (NPWT). They emphasize that NPWT eliminates wound
      exudate, promotes neovascularisation and cell migration through the Integra((r))
      matrix while increasing its stability and adherence to the wound bed, as well as
      decreasing the time needed for its total integration. The case presented here is
      of a patient with major third-degree flame burns to the lower extremities. After
      debridement, the external and internal malleolus bilaterally became exposed as
      well as the partially debrided tendons (Achilles, extensor digitorum longus, long
      and short peroneus, anterior and posterior tibialis). After ruling out the use of
      local or microsurgical flaps due to the patient's poor general condition and the
      presence of burns debrided to the fascia over both lower extremities, we elected
      to manage the patient with a combined treatment using Integra((r)) and NPWT.
      After three weeks of treatment, the surface layer of the Integra((r)) matrix was
      replaced with autografts. Due to partial loss of the skin grafts, a second
      autograft was needed. At present the patient is completely healed; he can walk
      with full flexion-extension of both ankles. 

PMID- 24133404
TI  - The use of Biobrane(r) to dress split-thickness skin graft in paediatric burns.
AB  - Biobrane((r)) is commonly used in paediatric burns to cover partial thickness
      burns and donor sites of split thickness skin (SSG). The purpose of this study is
      to evaluate the use of Biobrane((r)) in dressing SSG adjacent to skin graft donor
      sites or partial thickness burns. A retrospective review was undertaken to
      determine the use of Biobrane((r)) in dressing SSG, where the grafted areas were
      adjacent to donor sites or partial thickness burns. Between 2009 and 2012, we
      reported five cases of using Biobrane((r)) to dress SSG, where the grafted areas
      were adjacent to partial thickness burns and two cases where the grafted areas
      were adjacent to donor sites. Biobrane((r)) promoted adherence of the SSG to the
      wound, prevented shearing, and allowed fluid drainage. At the same time,
      Biobrane((r)) also facilitated healing of the adjacent donor sites or partial
      thickness burns. 

PMID- 24133406
TI  - MBC News.

PMID- 24133405
TI  - Advantages of collagen based biological dressings in the management of
      superficial and superficial partial thickness burns in children.
AB  - Collagen based dressings for acute burn wound management have been extensively
      used in India, particularly in the city of Chennai. Due to the high levels of
      humidity in our city, closed dressings become infected and treatment with topical
      antimicrobials, like Silver Sulfadiazine cream, quickly become desiccated.
      Collagen membrane dressings were manufactured by the biomaterial laboratory of
      the Central Leather Research Institute (CLRI), Government of India in Chennai,
      and then the process was patented. Collagen was extracted from bovine skin and
      Achilles tendons, and then reconstituted. This was used on burn wounds as
      dressings after clearance from the Institutional Review Board and Ethics
      Committees of the Hospital and CLRI. Continued research in this field to enable
      resulted in the design of silver sulphadiazine loaded alginate microspheres which
      were embedded in the reconstituted collagen. Controlled delivery of silver
      sulphadiazine. This collagen membrane was used in chronic infected burns. Low
      molecular weight heparin was given subcutaneously to improve wound healing in
      burn injuries and collagen membrane dressings were also applied. After several
      trials the process technology was patented. The advantages and disadvantages of
      the collagen membrane cover is elaborated in a group of 487 pediatric burn
      patients. The trial was conducted at the burn unit of Kanchi Kamakoti Childs
      Trust Hospital (KKCTH) in Chennai, India. 

PMID- 24133407
TI  - The central GLP-1: implications for food and drug reward.
AB  - Glucagon-like-peptide-1 (GLP-1) and its long acting analogs comprise a novel
      class of type 2 diabetes (T2D) treatment. What makes them unique among other T2D
      drugs is their concurrent ability to reduce food intake, a great benefit
      considering the frequent comorbidity of T2D and obesity. The precise neural site
      of action underlying this beneficial effect is vigorously researched. In
      accordance with the classical model of food intake control GLP-1 action on
      feeding has been primarily ascribed to receptor populations in the hypothalamus
      and the hindbrain. In contrast to this common view, relevant GLP-1 receptor
      populations are distributed more widely, with a prominent mesolimbic complement
      emerging. The physiological relevance of the mesolimbic GLP-1 is suggested by the
      demonstration that similar anorexic effects can be obtained by independent
      stimulation of the mesolimbic and hypothalamic GLP-1 receptors (GLP-1R). Results
      reviewed here support the idea that mesolimbic GLP-1R are sufficient to reduce
      hunger-driven feeding, the hedonic value of food and food-motivation. In
      parallel, emerging evidence suggests that the range of action of GLP-1 on reward
      behavior is not limited to food-derived reward but extends to cocaine,
      amphetamine, and alcohol reward. The new discoveries concerning GLP-1 action on
      the mesolimbic reward system significantly extend the potential therapeutic range
      of this drug target. 

PMID- 24133409
TI  - Characteristics of colonic migrating motor complexes in neuronal NOS (nNOS)
      knockout mice.
AB  - It is well established that the intrinsic pacemaker mechanism that generates
      cyclical colonic migrating motor complexes (CMMCs) does not require endogenous
      nitric oxide (NO). However, pharmacological blockade of endogenous NO production
      potently increases the frequency of CMMCs, suggesting that endogenous NO acts
      normally to inhibit the CMMC pacemaker mechanism. In this study, we investigated
      whether mice with a life long genetic deletion of the neuronal nitric oxide
      synthase (nNOS) gene would show similar CMMC characteristics as wild type mice
      that have endogenous NO production acutely inhibited. Intracellular
      electrophysiological and mechanical recordings were made from circular muscle
      cells of isolated whole mouse colon in wild type and nNOS knockout (KO) mice at
      35 degrees C. In wild type mice, the NOS inhibitor, L-NA (100 MUM) caused a
      significant increase in CMMC frequency and a significant depolarization of the CM
      layer. However, unexpectedly, the frequency of CMMCs in nNOS KO mice was not
      significantly different from control mice. Also, the resting membrane potential
      of CM cells in nNOS KO mice was not depolarized compared to controls; and the
      amplitude of the slow depolarization phase underlying MCs was of similar
      amplitude between KO and wild type offspring. These findings show that in nNOS KO
      mice, the major characteristics of CMMCs and their electrical correlates are, at
      least in adult mice, indistinguishable from wild type control offspring. One
      possibility why the major characteristics of CMMCs were no different between both
      types of mice is that nNOS KO mice may compensate for their life long deletion of
      the nNOS gene, and their permanent loss of neuronal NO production. In this
      regard, we suggest caution should be exercised when assuming that data obtained
      from adult nNOS KO mice can be directly extrapolated to wild type mice, that have
      been acutely exposed to an inhibitor of NOS. 

PMID- 24133408
TI  - Brain immune interactions and air pollution: macrophage inhibitory factor (MIF),
      prion cellular protein (PrP(C)), Interleukin-6 (IL-6), interleukin 1 receptor
      antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in
      serum differentiate urban children exposed to severe vs. low air pollution.
AB  - Mexico City Metropolitan Area children chronically exposed to high concentrations
      of air pollutants exhibit an early brain imbalance in genes involved in oxidative
      stress, inflammation, innate and adaptive immune responses along with
      accumulation of misfolded proteins observed in the early stages of Alzheimer and
      Parkinson's diseases. A complex modulation of serum cytokines and chemokines
      influences children's brain structural and gray/white matter volumetric responses
      to air pollution. The search for biomarkers associating systemic and CNS
      inflammation to brain growth and cognitive deficits in the short term and
      neurodegeneration in the long-term is our principal aim. We explored and compared
      a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and
      Cellular prion protein (PrP(C)) in normal cerebro-spinal-fluid (CSF) of urban
      children with high vs. low air pollution exposures. PrP(C) and macrophage
      inhibitory factor (MIF) were also measured in serum. Samples from 139 children
      ages 11.91 +/- 4.2 years were measured. Highly exposed children exhibited
      significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014),
      IL-2 (p = 0.04), and PrP(C) (p = 0.039) vs. controls. MIF serum concentrations
      were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF,
      IL6, IL1Ra, IL-2, and PrP(C) compartment that can possibly differentiate air
      pollution exposures in children. MIF, a key neuro-immune mediator, is a potential
      biomarker bridge to identify children with CNS inflammation. Fine tuning of
      immune-to-brain communication is crucial to neural networks appropriate
      functioning, thus the short and long term effects of systemic inflammation and
      dysregulated neural immune responses are of deep concern for millions of exposed
      children. Defining the linkage and the health consequences of the brain / immune
      system interactions in the developing brain chronically exposed to air pollutants
      ought to be of pressing importance for public health. 

PMID- 24133410
TI  - Circadian adaptations to meal timing: neuroendocrine mechanisms.
AB  - Circadian rhythms of behavior and physiology are generated by central and
      peripheral circadian oscillators entrained by periodic environmental or
      physiological stimuli. A master circadian pacemaker in the hypothalamic
      suprachiasmatic nucleus (SCN) is directly entrained by daily light-dark (LD)
      cycles, and coordinates the timing of other oscillators by direct and indirect
      neural, hormonal and behavioral outputs. The daily rhythm of food intake provides
      stimuli that entrain most peripheral and central oscillators, some of which can
      drive a daily rhythm of food anticipatory activity if food is restricted to one
      daily mealtime. The location of food-entrainable oscillators (FEOs) that drive
      food anticipatory rhythms, and the food-related stimuli that entrain these
      oscillators, remain to be clarified. Here, we critically examine the role of
      peripheral metabolic hormones as potential internal entrainment stimuli or
      outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones
      for which data are available include corticosterone, ghrelin, leptin, insulin,
      glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily
      rhythms of synthesis and secretion that are synchronized by meal timing. There is
      some evidence that ghrelin and leptin modulate the expression of food
      anticipatory rhythms, but none of the hormones examined so far are necessary for
      entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions
      in hypothalamic circuits utilizing melanocortin and orexin signaling, although
      again food-entrained behavioral rhythms can persist in lesion and gene knockout
      models in which these systems are disabled. Actions of these hormones on
      circadian oscillators in central reward circuits remain to be evaluated. Food
      entrained activity rhythms are likely mediated by a distributed system of
      circadian oscillators sensitive to multiple feeding related inputs. Metabolic
      hormones appear to play a modulatory role within this system. 

PMID- 24133411
TI  - Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during
      late mouse embryogenesis through EGFR transactivation.
AB  - Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell
      (NSC) proliferation. How these signals cooperate is therefore critical for
      understanding normal brain development and function. Here we report a novel acute
      effect of Shh signaling on EGFR function. We show that during late neocortex
      development, Shh mediates the activation of the ERK1/2 signaling pathway in
      Radial Glial cells (RGC) through EGFR transactivation. This process is dependent
      on metalloprotease activity and accounts for almost 50% of the EGFR-dependent
      mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known
      model for studying the EGFR receptor function, Shh also induces cell
      proliferation involving EGFR activation, as reflected by EGFR internalization and
      ERK1/2 phosphorylation. These findings may have important implications for
      understanding the mechanisms that regulate NSC proliferation during neurogenesis
      and may lead to novel approaches to the treatment of tumors. 

PMID- 24133412
TI  - MARCH5 inactivation supports mitochondrial function during neurodegenerative
      stress.
AB  - Neuronal cell death is accompanied by mitochondrial dysfunction with
      mitochondrial maintenance critical to neuronal survival. The mitochondrial
      ubiquitin ligase MARCH5 has dual roles in the upkeep of mitochondrial function.
      MARCH5 is involved in targeted degradation of proteins harmful to mitochondria
      and impacts mitochondrial morphology upstream of the fission protein Drp1. In a
      neuronal cell model, dominant-negative MARCH5 prevents mitochondrial
      fragmentation during neurodegenerative stress induced by the neuron-specific
      reactive oxygen generator 6-hydroxydopamine, the complex I inhibitor rotenone or
      Alzheimer's-related amyloid beta peptide. In addition, preservation of
      mitochondrial function in terms of membrane potential and lower reactive oxygen
      generation was observed following inactivation of MARCH5. Our findings connect
      MARCH5 to neuronal stress responses and further emphasize the link between
      mitochondrial dynamics and function. 

PMID- 24133413
TI  - Neuronal dark matter: the emerging role of microRNAs in neurodegeneration.
AB  - MicroRNAs (miRNAs) are small, abundant RNA molecules that constitute part of the
      cell's non-coding RNA "dark matter." In recent years, the discovery of miRNAs has
      revolutionised the traditional view of gene expression and our understanding of
      miRNA biogenesis and function has expanded. Altered expression of miRNAs is
      increasingly recognized as a feature of many disease states, including
      neurodegeneration. Here, we review the emerging role for miRNA dysfunction in
      Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and
      Huntington's disease pathogenesis. We emphasize the complex nature of gene
      regulatory networks and the need for systematic studies, with larger sample
      cohorts than have so far been reported, to reveal the most important miRNA
      regulators in disease. Finally, miRNA diversity and their potential to target
      multiple pathways, offers novel clinical applications for miRNAs as biomarkers
      and therapeutic agents in neurodegenerative diseases. 

PMID- 24133414
TI  - Three-dimensional mapping of microcircuit correlation structure.
AB  - Great progress has been made toward understanding the properties of single
      neurons, yet the principles underlying interactions between neurons remain poorly
      understood. Given that connectivity in the neocortex is locally dense through
      both horizontal and vertical connections, it is of particular importance to
      characterize the activity structure of local populations of neurons arranged in
      three dimensions. However, techniques for simultaneously measuring microcircuit
      activity are lacking. We developed an in vivo 3D high-speed, random-access two
      photon microscope that is capable of simultaneous 3D motion tracking. This allows
      imaging from hundreds of neurons at several hundred Hz, while monitoring tissue
      movement. Given that motion will induce common artifacts across the population,
      accurate motion tracking is absolutely necessary for studying population activity
      with random-access based imaging methods. We demonstrate the potential of this
      imaging technique by measuring the correlation structure of large populations of
      nearby neurons in the mouse visual cortex, and find that the microcircuit
      correlation structure is stimulus-dependent. Three-dimensional random access
      multiphoton imaging with concurrent motion tracking provides a novel, powerful
      method to characterize the microcircuit activity in vivo. 

PMID- 24133416
TI  - Neurites containing the neurofilament-triplet proteins are selectively vulnerable
      to cytoskeletal pathology in Alzheimer's disease and transgenic mouse models.
AB  - Amyloid-beta plaque accumulation in Alzheimer's disease (AD) is associated with
      dystrophic neurite (DN) formation and synapse loss in principal neurons, but
      interneuron pathology is less clearly characterized. We compared the responses of
      neuronal processes immunoreactive for either neurofilament triplet (NF(+)) or
      calretinin (CR(+)) to fibrillar amyloid (Abeta) plaques in human end-stage and
      preclinical AD, as well as in APP/PS1 and Tg2576 transgenic mouse AD models.
      Neurites traversing the Abeta plaque core, edge, or periphery, defined as 50,
      100, and 150% of the plaque diameter, respectively, in human AD and transgenic
      mouse tissue were compared to age-matched human and wild-type mouse controls. The
      proportion of NF(+) neurites exhibiting dystrophic morphology (DN) was
      significantly larger than the proportion of dystrophic CR(+) neurites in both
      human AD and transgenic mice (p < 0.01). Additionally, the number of NF(+), but
      not CR(+), DNs, correlated with Abeta plaque size. We conclude that CR(+)
      interneurons appear to be more resistant than NF(+) neurons to AD-mediated
      cytoskeletal pathology. 

PMID- 24133417
TI  - Development and automation of a test of impulse control in zebrafish.
AB  - Deficits in impulse control (difficulties in inhibition of a pre-potent response)
      are fundamental to a number of psychiatric disorders, but the molecular and
      cellular basis is poorly understood. Zebrafish offer a very useful model for
      exploring these mechanisms, but there is currently a lack of validated procedures
      for measuring impulsivity in fish. In mammals, impulsivity can be measured by
      examining rates of anticipatory responding in the 5-choice serial reaction time
      task (5-CSRTT), a continuous performance task where the subject is reinforced
      upon accurate detection of a briefly presented light in one of five distinct
      spatial locations. This paper describes the development of a fully-integrated
      automated system for testing impulsivity in adult zebrafish. We outline the
      development of our image analysis software and its integration with National
      Instruments drivers and actuators to produce the system. We also describe an
      initial validation of the system through a one-generation screen of chemically
      mutagenized zebrafish, where the testing parameters were optimized. 

PMID- 24133415
TI  - Application of FRET probes in the analysis of neuronal plasticity.
AB  - Breakthroughs in imaging techniques and optical probes in recent years have
      revolutionized the field of life sciences in ways that traditional methods could
      never match. The spatial and temporal regulation of molecular events can now be
      studied with great precision. There have been several key discoveries that have
      made this possible. Since green fluorescent protein (GFP) was cloned in 1992, it
      has become the dominant tracer of proteins in living cells. Then the evolution of
      color variants of GFP opened the door to the application of Forster resonance
      energy transfer (FRET), which is now widely recognized as a powerful tool to
      study complicated signal transduction events and interactions between molecules.
      Employment of fluorescent lifetime imaging microscopy (FLIM) allows the precise
      detection of FRET in small subcellular structures such as dendritic spines. In
      this review, we provide an overview of the basic and practical aspects of FRET
      imaging and discuss how different FRET probes have revealed insights into the
      molecular mechanisms of synaptic plasticity and enabled visualization of neuronal
      network activity both in vitro and in vivo. 

PMID- 24133418
TI  - Serotonergic modulation of spatial working memory: predictions from a
      computational network model.
AB  - Serotonin (5-HT) receptors of types 1A and 2A are strongly expressed in
      prefrontal cortex (PFC) neurons, an area associated with cognitive function.
      Hence, 5-HT could be effective in modulating prefrontal-dependent cognitive
      functions, such as spatial working memory (SWM). However, a direct association
      between 5-HT and SWM has proved elusive in psycho-pharmacological studies.
      Recently, a computational network model of the PFC microcircuit was used to
      explore the relationship between 5-HT and SWM (Cano-Colino et al., 2013). This
      study found that both excessive and insufficient 5-HT levels lead to impaired SWM
      performance in the network, and it concluded that analyzing behavioral responses
      based on confidence reports could facilitate the experimental identification of
      SWM behavioral effects of 5-HT neuromodulation. Such analyses may have confounds
      based on our limited understanding of metacognitive processes. Here, we extend
      these results by deriving three additional predictions from the model that do not
      rely on confidence reports. Firstly, only excessive levels of 5-HT should result
      in SWM deficits that increase with delay duration. Secondly, excessive 5-HT
      baseline concentration makes the network vulnerable to distractors at distances
      that were robust to distraction in control conditions, while the network still
      ignores distractors efficiently for low 5-HT levels that impair SWM. Finally, 5
      HT modulates neuronal memory fields in neurophysiological experiments: Neurons
      should be better tuned to the cued stimulus than to the behavioral report for
      excessive 5-HT levels, while the reverse should happen for low 5-HT
      concentrations. In all our simulations agonists of 5-HT1A receptors and
      antagonists of 5-HT2A receptors produced behavioral and physiological effects in
      line with global 5-HT level increases. Our model makes specific predictions to be
      tested experimentally and advance our understanding of the neural basis of SWM
      and its neuromodulation by 5-HT receptors. 

PMID- 24133419
TI  - Modified impact of emotion on temporal discrimination in a transgenic rat model
      of Huntington disease.
AB  - Huntington's disease (HD) is characterized by triad of motor, cognitive, and
      emotional symptoms along with neuropathology in fronto-striatal circuit and
      limbic system including amygdala. Emotional alterations, which have a negative
      impact on patient well-being, represent some of the earliest symptoms of HD and
      might be related to the onset of the neurodegenerative process. In the transgenic
      rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic
      stage along with neuropathology of the central nucleus of amygdala (CE). Studies
      in humans and animals demonstrate that emotion can modulate time perception. The
      impact of emotion on time perception has never been tested in HD, nor is it known
      if that impact could be part of the presymptomatic emotional phenotype of the
      pathology. The aim of this paper was to characterize the effect of emotion on
      temporal discrimination in presymptomatic tgHD animals. In the first experiment,
      we characterized the acute effect of an emotion (fear) conditioned stimulus on
      temporal discrimination using a bisection procedure, and tested its dependency
      upon an intact central amygdala. The second experiment was aimed at comparing
      presymptomatic homozygous transgenic animals at 7-months of age and their wild
      type littermates (WT) in their performance on the modulation of temporal
      discrimination by emotion. Our principal findings show that (1) a fear cue
      produces a short-lived decrease of temporal precision after its termination, and
      (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an
      alteration of this emotion-evoked temporal distortion. The results contribute to
      our knowledge about the presymptomatic phenotype of this HD rat model, showing
      susceptibility to emotion that may be related to dysfunction of the central
      nucleus of amygdala. 

PMID- 24133420
TI  - Urethane anesthesia depresses activities of thalamocortical neurons and alters
      its response to nociception in terms of dual firing modes.
AB  - Anesthetics are often used to characterize the activity of single neurons in vivo
      for their advantages such as reduction of noise level and convenience in noxious
      stimulations. Urethane has been a widely used anesthetic in thalamic studies
      under the assumption that sensory signals are still relayed to the thalamus under
      urethane anesthesia and that thalamic response would therefore reflect the
      response of the awake state. We tested this assumption by comparing thalamic
      activity in terms of tonic and burst firing modes during "the awake state" or
      under "urethane anesthesia" using the extracellular single unit recording
      technique. We first tested how thalamic relay neurons respond to the introduction
      of urethane, and then tested how urethane influences thalamic discharges under
      formalin-induced nociception. Urethane significantly depressed overall firing
      rates of thalamic relay neurons, which was sustained despite the delayed increase
      of burst activity over a 4 h recording period. Thalamic response to nociception
      under anesthesia was also similar overall except for the slight and transient
      increase of burst activity. Overall, results demonstrated that urethane
      suppresses the activity of thalamic relay neurons and that, despite the slight
      fluctuation of burst firing, formalin-induced nociception cannot significantly
      change the firing pattern of thalamic relay neurons that was caused by urethane. 

PMID- 24133421
TI  - Orexin receptors within the nucleus accumbens shell mediate the stress but not
      drug priming-induced reinstatement of morphine conditioned place preference.
AB  - Orexins are found to participate in mediating stress-induced drug relapse.
      However, the neuroanatomical basis that orexin transmission modulates stress
      induced drug seeking remains unknown. The nucleus accumbens shell (NAcSh), best
      known for its role in appetitive and negative motivation via dopamine receptors,
      is likely to be the potential important brain area where the orexin system
      mediates stress-induced drug relapse since the function of dopamine system in the
      NAcSh can be regulated by orexin transmission. In the present study, a morphine
      conditioned place preference (CPP) model was used to determine whether the two
      types of orexin receptors would be involved into footshock-induced and/or drug
      priming-induced CPP reinstatement differentially. The results showed that
      blockade of orexin-1 or orexin-2 receptor in the NAcSh significantly attenuated
      stress-induced morphine CPP reinstatement, but neither of the orexin antagonists
      had any effect on morphine priming-induced reinstatement. These findings indicate
      that the NAcSh is a brain area through which orexins participate in stress but
      not drug priming-induced relapse of opioid seeking. 

PMID- 24133422
TI  - Alerting, orienting or executive attention networks: differential patters of
      pupil dilations.
AB  - Attention capacities, alerting responses, orienting to sensory stimulation, and
      executive monitoring of performance are considered independent yet interrelated
      systems. These operations play integral roles in regulating the behavior of
      diverse species along the evolutionary ladder. Each of the primary attention
      constructs-alerting, orienting, and executive monitoring-involves salient
      autonomic correlates as evidenced by changes in reactive pupil dilation (PD),
      heart rate, and skin conductance. Recent technological advances that use remote
      high-resolution recording may allow the discernment of temporo-spatial attributes
      of autonomic responses that characterize the alerting, orienting, and executive
      monitoring networks during free viewing, irrespective of voluntary performance.
      This may deepen the understanding of the roles of autonomic regulation in these
      mental operations and may deepen our understanding of behavioral changes in
      verbal as well as in non-verbal species. The aim of this study was to explore
      differences between psychosensory PD responses in alerting, orienting, and
      executive conflict monitoring tasks to generate estimates of concurrent locus
      coeruleus (LC) noradrenergic input trajectories in healthy human adults using the
      attention networks test (ANT). The analysis revealed a construct-specific pattern
      of pupil responses: alerting is characterized by an early component (Pa), its
      acceleration enables covert orienting, and executive control is evidenced by a
      prominent late component (Pe). PD characteristics seem to be task-sensitive,
      allowing exploration of mental operations irrespective of conscious voluntary
      responses. These data may facilitate development of studies designed to assess
      mental operations in diverse species using autonomic responses. 

PMID- 24133423
TI  - Cognitively controlled timing and executive functions develop in parallel? A
      glimpse on childhood research.

PMID- 24133424
TI  - Opioid and dopamine mediation of gambling responses in recreational gamblers.

PMID- 24133425
TI  - Abnormal functional connectivity during visuospatial processing is associated
      with disrupted organisation of white matter in autism.
AB  - Disruption of structural and functional neural connectivity has been widely
      reported in Autism Spectrum Disorder (ASD) but there is a striking lack of
      research attempting to integrate analysis of functional and structural
      connectivity in the same study population, an approach that may provide key
      insights into the specific neurobiological underpinnings of altered functional
      connectivity in autism. The aims of this study were (1) to determine whether
      functional connectivity abnormalities were associated with structural
      abnormalities of white matter (WM) in ASD and (2) to examine the relationships
      between aberrant neural connectivity and behavior in ASD. Twenty-two individuals
      with ASD and 22 age, IQ-matched controls completed a high-angular-resolution
      diffusion MRI scan. Structural connectivity was analysed using constrained
      spherical deconvolution (CSD) based tractography. Regions for tractography were
      generated from the results of a previous study, in which 10 pairs of brain
      regions showed abnormal functional connectivity during visuospatial processing in
      ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal
      functional connectivity; linking a region in the left occipital lobe (left BA19)
      and five paired regions: left caudate head, left caudate body, left uncus, left
      thalamus, and left cuneus. Measures of WM microstructural organization were
      extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD
      group relative to controls were significant for WM connecting left BA19 to left
      caudate head and left BA19 to left thalamus. Using a multimodal imaging approach,
      this study has revealed aberrant WM microstructure in tracts that directly
      connect brain regions that are abnormally functionally connected in ASD. These
      results provide novel evidence to suggest that structural brain pathology may
      contribute (1) to abnormal functional connectivity and (2) to atypical
      visuospatial processing in ASD. 

PMID- 24133427
TI  - Kinesthetic imagery training of forceful muscle contractions increases brain
      signal and muscle strength.
AB  - The purpose of this study was to compare the effect of training using internal
      imagery (IMI; also known as kinesthetic imagery or first person imagery) with
      that of external imagery (EMI; also known as third-person visual imagery) of
      strong muscle contractions on voluntary muscle strengthening. Eighteen young,
      healthy subjects were randomly assigned to one of three groups (6 in each group):
      internal motor imagery (IMI), external motor imagery (EMI), or a no-practice
      control (CTRL) group. Training lasted for 6 weeks (~15 min/day, 5 days/week). The
      participants' right arm elbow-flexion strength, muscle electrical activity, and
      movement-related cortical potential (MRCP) were evaluated before and after
      training. Only the IMI group showed significant strength gained (10.8%) while the
      EMI (4.8%) and CTRL (-3.3%) groups did not. Only the IMI group showed a
      significant elevation in MRCP on scalp locations over both the primary motor (M1)
      and supplementary motor cortices (EMI group over M1 only) and this increase was
      significantly greater than that of EMI and CTRL groups. These results suggest
      that training by IMI of forceful muscle contractions was effective in improving
      voluntary muscle strength without physical exercise. We suggest that the IMI
      training likely strengthened brain-to-muscle (BTM) command that may have improved
      motor unit recruitment and activation, and led to greater muscle output. Training
      by IMI of forceful muscle contractions may change the activity level of cortical
      motor control network, which may translate into greater descending command to the
      target muscle and increase its strength. 

PMID- 24133426
TI  - The implicit processing of categorical and dimensional strategies: an fMRI study
      of facial emotion perception.
AB  - OUR UNDERSTANDING OF FACIAL EMOTION PERCEPTION HAS BEEN DOMINATED BY TWO
      SEEMINGLY OPPOSING THEORIES: the categorical and dimensional theories. However,
      we have recently demonstrated that hybrid processing involving both categorical
      and dimensional perception can be induced in an implicit manner (Fujimura etal.,
      2012). The underlying neural mechanisms of this hybrid processing remain unknown.
      In this study, we tested the hypothesis that separate neural loci might
      intrinsically encode categorical and dimensional processing functions that serve
      as a basis for hybrid processing. We used functional magnetic resonance imaging
      to measure neural correlates while subjects passively viewed emotional faces and
      performed tasks that were unrelated to facial emotion processing. Activity in the
      right fusiform face area (FFA) increased in response to psychologically obvious
      emotions and decreased in response to ambiguous expressions, demonstrating the
      role of the FFA in categorical processing. The amygdala, insula and medial
      prefrontal cortex exhibited evidence of dimensional (linear) processing that
      correlated with physical changes in the emotional face stimuli. The occipital
      face area and superior temporal sulcus did not respond to these changes in the
      presented stimuli. Our results indicated that distinct neural loci process the
      physical and psychological aspects of facial emotion perception in a region
      specific and implicit manner. 

PMID- 24133428
TI  - Predictive error detection in pianists: a combined ERP and motion capture study.
AB  - Performing a piece of music involves the interplay of several cognitive and motor
      processes and requires extensive training to achieve a high skill level. However,
      even professional musicians commit errors occasionally. Previous event-related
      potential (ERP) studies have investigated the neurophysiological correlates of
      pitch errors during piano performance, and reported pre-error negativity already
      occurring approximately 70-100 ms before the error had been committed and
      audible. It was assumed that this pre-error negativity reflects predictive
      control processes that compare predicted consequences with actual consequences of
      one's own actions. However, in previous investigations, correct and incorrect
      pitch events were confounded by their different tempi. In addition, no data about
      the underlying movements were available. In the present study, we exploratively
      recorded the ERPs and 3D movement data of pianists' fingers simultaneously while
      they performed fingering exercises from memory. Results showed a pre-error
      negativity for incorrect keystrokes when both correct and incorrect keystrokes
      were performed with comparable tempi. Interestingly, even correct notes
      immediately preceding erroneous keystrokes elicited a very similar negativity. In
      addition, we explored the possibility of computing ERPs time-locked to a
      kinematic landmark in the finger motion trajectories defined by when a finger
      makes initial contact with the key surface, that is, at the onset of tactile
      feedback. Results suggest that incorrect notes elicited a small difference after
      the onset of tactile feedback, whereas correct notes preceding incorrect ones
      elicited negativity before the onset of tactile feedback. The results tentatively
      suggest that tactile feedback plays an important role in error-monitoring during
      piano performance, because the comparison between predicted and actual sensory
      (tactile) feedback may provide the information necessary for the detection of an
      upcoming error. 

PMID- 24133430
TI  - Methodological lessons in neurophenomenology: Review of a baseline study and
      recommendations for research approaches.
AB  - Neurophenomenological (NP) methods integrate objective and subjective data in
      ways that retain the statistical power of established disciplines (like cognitive
      science) while embracing the value of first-person reports of experience. The
      present paper positions neurophenomenology as an approach that pulls from
      traditions of cognitive science but includes techniques that are challenging for
      cognitive science in some ways. A baseline study is reviewed for "lessons
      learned," that is, the potential methodological improvements that will support
      advancements in understanding consciousness and cognition using
      neurophenomenology. These improvements, we suggest, include (1) addressing issues
      of interdisciplinarity by purposefully and systematically creating and
      maintaining shared mental models among research team members; (2) making sure
      that NP experiments include high standards of experimental design and execution
      to achieve variable control, reliability, generalizability, and replication of
      results; and (3) conceiving of phenomenological interview techniques as placing
      the impetus on the interviewer in interaction with the experimental subject. 

PMID- 24133429
TI  - Sex differences in chemosensation: sensory or emotional?
AB  - Although the first sex-dependent differences in chemosensory processing were
      reported in the scientific literature over 60 years ago, the underlying
      mechanisms are still unknown. Generally, more pronounced sex-dependent
      differences are noted with increased task difficulty or with increased levels of
      intranasal irritation produced by the stimulus. Whether differences between the
      sexes arise from differences in chemosensory sensitivity of the two intranasal
      sensory systems involved or from differences in cognitive processing associated
      with emotional evaluation of the stimulants is still not known. We used
      simultaneous and complementary measures of electrophysiological (EEG),
      psychophysiological, and psychological responses to stimuli varying in intranasal
      irritation and odorousness to investigate whether sex differences in the
      processing of intranasal irritation are mediated by varying sensitivity of the
      involved sensory systems or by differences in cognitive and/or emotional
      evaluation of the irritants. Women perceived all stimulants more irritating and
      they exhibited larger amplitudes of the late positive deflection of the event
      related potential than men. No significant differences in sensory sensitivity,
      anxiety, and arousal responses could be detected. Our findings suggest that men
      and women process intranasal irritation differently. Importantly, the differences
      cannot be explained by variation in sensory sensitivity to irritants, differences
      in anxiety, or differences in physiological arousal. We propose that women
      allocate more attention to potentially noxious stimuli than men do, which
      eventually causes differences in cognitive appraisal and subjective perception. 

PMID- 24133431
TI  - Contribution of transcranial oscillatory stimulation to research on neural
      networks: an emphasis on hippocampo-neocortical rhythms.
AB  - EEG rhythms reflect the synchronized activity of underlying biological neuronal
      network oscillations, and certain predominant frequencies are typically linked to
      certain behavioral states. For instance, slow wave activity characterized by
      sleep slow oscillation (SO) emerges normally during slow-wave sleep (SWS). In
      this mini-review we will first give a background leading up to the present day
      association between specific oscillations and their functional relevance for
      learning and memory consolidation. Following, some principles on oscillatory
      activity are summarized and finally results of studies employing slowly
      oscillating transcranial electric stimulation are given. We underscore that
      oscillatory transcranial electric stimulation presents a tool to study principles
      of cortical network function. 

PMID- 24133432
TI  - Flexible spatial perspective-taking: conversational partners weigh multiple cues
      in collaborative tasks.
AB  - Research on spatial perspective-taking often focuses on the cognitive processes
      of isolated individuals as they adopt or maintain imagined perspectives.
      Collaborative studies of spatial perspective-taking typically examine speakers'
      linguistic choices, while overlooking their underlying processes and
      representations. We review evidence from two collaborative experiments that
      examine the contribution of social and representational cues to spatial
      perspective choices in both language and the organization of spatial memory.
      Across experiments, speakers organized their memory representations according to
      the convergence of various cues. When layouts were randomly configured and did
      not afford intrinsic cues, speakers encoded their partner's viewpoint in memory,
      if available, but did not use it as an organizing direction. On the other hand,
      when the layout afforded an intrinsic structure, speakers organized their spatial
      memories according to the person-centered perspective reinforced by the layout's
      structure. Similarly, in descriptions, speakers considered multiple cues whether
      available a priori or at the interaction. They used partner-centered expressions
      more frequently (e.g., "to your right") when the partner's viewpoint was
      misaligned by a small offset or coincided with the layout's structure.
      Conversely, they used egocentric expressions more frequently when their own
      viewpoint coincided with the intrinsic structure or when the partner was
      misaligned by a computationally difficult, oblique offset. Based on these
      findings we advocate for a framework for flexible perspective-taking: people
      weigh multiple cues (including social ones) to make attributions about the
      relative difficulty of perspective-taking for each partner, and adapt behavior to
      minimize their collective effort. This framework is not specialized for spatial
      reasoning but instead emerges from the same principles and memory-depended
      processes that govern perspective-taking in non-spatial tasks. 

PMID- 24133433
TI  - Valence of emotions and moral decision-making: increased pleasantness to pleasant
      images and decreased unpleasantness to unpleasant images are associated with
      utilitarian choices in healthy adults.
AB  - Moral decision-making is a key asset for humans' integration in social contexts,
      and the way we decide about moral issues seems to be strongly influenced by
      emotions. For example, individuals with deficits in emotional processing tend to
      deliver more utilitarian choices (accepting an emotionally aversive action in
      favor of communitarian well-being). However, little is known about the
      association between emotional experience and moral-related patterns of choice. We
      investigated whether subjective reactivity to emotional stimuli, in terms of
      valence, arousal, and dominance, is associated with moral decision-making in 95
      healthy adults. They answered to a set of moral and non-moral dilemmas and
      assessed emotional experience in valence, arousal and dominance dimensions in
      response to neutral, pleasant, unpleasant non-moral, and unpleasant moral
      pictures. Results showed significant correlations between less unpleasantness to
      negative stimuli, more pleasantness to positive stimuli and higher proportion of
      utilitarian choices. We also found a positive association between higher arousal
      ratings to negative moral laden pictures and more utilitarian choices. Low
      dominance was associated with greater perceived difficulty over moral judgment.
      These behavioral results are in fitting with the proposed role of emotional
      experience in moral choice. 

PMID- 24133435
TI  - Effects of saccadic bilateral eye movements on episodic and semantic
      autobiographical memory fluency.
AB  - Performing a sequence of fast saccadic horizontal eye movements has been shown to
      facilitate performance on a range of cognitive tasks, including the retrieval of
      episodic memories. One explanation for these effects is based on the hypothesis
      that saccadic eye movements increase hemispheric interaction, and that such
      interactions are important for particular types of memory. The aim of the current
      research was to assess the effect of horizontal saccadic eye movements on the
      retrieval of both episodic autobiographical memory (event/incident based memory)
      and semantic autobiographical memory (fact based memory) over recent and more
      distant time periods. It was found that saccadic eye movements facilitated the
      retrieval of episodic autobiographical memories (over all time periods) but not
      semantic autobiographical memories. In addition, eye movements did not enhance
      the retrieval of non-autobiographical semantic memory. This finding illustrates a
      dissociation between the episodic and semantic characteristics of personal memory
      and is considered within the context of hemispheric contributions to episodic
      memory performance. 

PMID- 24133434
TI  - Putative physiological mechanisms underlying tDCS analgesic effects.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation
      technique that induces changes in excitability, and activation of brain neurons
      and neuronal circuits. It has been observed that beyond regional effects under
      the electrodes, tDCS also alters activity of remote interconnected cortical and
      subcortical areas. This makes the tDCS stimulation technique potentially
      promising for modulation of pain syndromes. Indeed, utilizing specific montages,
      tDCS resulted in analgesic effects in experimental settings, as well as in post
      operative acute pain and chronic pain syndromes. The promising evidence of tDCS
      induced analgesic effects raises the challenging and complex question of
      potential physiologic mechanisms that underlie/mediate the accomplished pain
      relief. Here we present hypotheses on how the specific montages and targets for
      stimulation may affect the pain processing network. 

PMID- 24133436
TI  - Modulation of functionally localized right insular cortex activity using real
      time fMRI-based neurofeedback.
AB  - The capacity for subjects to learn to volitionally control localized brain
      activity using neurofeedback is actively being investigated. We aimed to
      investigate the ability of healthy volunteers to quickly learn to use visual
      feedback during real-time functional MRI (rtfMRI) to modulate brain activity
      within their anterior right insular cortex (RIC) localized during a blink
      suppression task, an approach of possible interest in the use of rtfMRI to reduce
      urges. The RIC region of interest (RIC-ROI) was functionally localized using a
      blink suppression task, and blood-oxygen level dependent (BOLD) signal changes
      within RIC-ROI used to create a constantly updating display fed back to the
      subject in the scanner. Subjects were instructed to use emotional imagery to try
      and increase activity within RIC-ROI during four feedback training runs (FB1
      FB4). A "control" run (CNTRL) before training and a "transfer" run (XSFR) after
      training were performed without feedback to assess for baseline abilities and
      learning effects. Fourteen participants completed all neurofeedback training
      runs. At the group-level, increased BOLD activity was seen in the anterior RIC
      during all the FB runs, but a significant increase in the functionally defined
      RIC-ROI was only attained during FB2. In atlas-defined insular cortex ROIs,
      significant increases were seen bilaterally during the CNTRL, FB1, FB2, and FB4
      runs. Increased activity within the insular cortices did not show lateralization.
      Training did, however, result in a significant increase in functional
      connectivity between the RIC-ROI and the medial frontal gyrus when comparing FB4
      to FB1. Since neurofeedback training did not lead to an increase in BOLD signal
      across all feedback runs, we suggest that learning to control one's brain
      activity in this fashion may require longer or repeated rtfMRI training sessions.

PMID- 24133437
TI  - Motor resonance facilitates movement execution: an ERP and kinematic study.
AB  - Action observation, simulation and execution share neural mechanisms that allow
      for a common motor representation. It is known that when these overlapping
      mechanisms are simultaneously activated by action observation and execution,
      motor performance is influenced by observation and vice versa. To understand the
      neural dynamics underlying this influence and to measure how variations in brain
      activity impact the precise kinematics of motor behavior, we coupled kinematics
      and electrophysiological recordings of participants while they performed and
      observed congruent or non-congruent actions or during action execution alone. We
      found that movement velocities and the trajectory deviations of the executed
      actions increased during the observation of congruent actions compared to the
      observation of non-congruent actions or action execution alone. This facilitation
      was also discernible in the motor-related potentials of the participants; the
      motor-related potentials were transiently more negative in the congruent
      condition around the onset of the executed movement, which occurred 300 ms after
      the onset of the observed movement. This facilitation seemed to depend not only
      on spatial congruency but also on the optimal temporal relationship of the
      observation and execution events. 

PMID- 24133438
TI  - The phenomenology of deep brain stimulation-induced changes in OCD: an enactive
      affordance-based model.
AB  - People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not
      want to do, and/or they think things they do not want to think. In about 10% of
      OCD patients, none of the available treatment options is effective. A small group
      of these patients is currently being treated with deep brain stimulation (DBS).
      DBS involves the implantation of electrodes in the brain. These electrodes give a
      continuous electrical pulse to the brain area in which they are implanted. It
      turns out that patients may experience profound changes as a result of DBS
      treatment. It is not just the symptoms that change; patients rather seem to
      experience a different way of being in the world. These global effects are
      insufficiently captured by traditional psychiatric scales, which mainly consist
      of behavioral measures of the severity of the symptoms. In this article we aim to
      capture the changes in the patients' phenomenology and make sense of the broad
      range of changes they report. For that we introduce an enactive, affordance-based
      model that fleshes out the dynamic interactions between person and world in four
      aspects. The first aspect is the patients' experience of the world. We propose to
      specify the patients' world in terms of a field of affordances, with the three
      dimensions of broadness of scope ("width" of the field), temporal horizon
      ("depth"), and relevance of the perceived affordances ("height"). The second
      aspect is the person-side of the interaction, that is, the patients' self
      experience, notably their moods and feelings. Thirdly, we point to the different
      characteristics of the way in which patients relate to the world. And lastly, the
      existential stance refers to the stance that patients take toward the changes
      they experience: the second-order evaluative relation to their interactions and
      themselves. With our model we intend to specify the notion of being in the world
      in order to do justice to the phenomenological effects of DBS treatment. 

PMID- 24133439
TI  - Genome-wide association study of autistic-like traits in a general population
      study of young adults.
AB  - Lay abstract: It has been proposed that autistic-like traits in the general
      population lie on a continuum, with clinical Autism Spectrum Disorder (ASD),
      representing the extreme end of this distribution. The current study undertook a
      genome-wide association (GWA) scan of 965 young Western Australian adults to
      identify novel risk variants associated with autistic-like traits. No
      associations reached genome-wide significance; however, a review of nominally
      associated single nucleotide polymorphisms (SNPs) indicated two positional
      candidate loci that have been previously implicated in autistic-like trait
      etiology. Scientific abstract: Research has proposed that autistic-like traits in
      the general population lie on a continuum, with clinical ASD representing the
      extreme end of this distribution. Inherent in this proposal is that biological
      mechanisms associated with clinical ASD may also underpin variation in autistic
      like traits within the general population. A GWA study using 2,462,046 SNPs was
      undertaken for ASD in 965 individuals from the Western Australian Pregnancy
      Cohort (Raine) Study. No SNP associations reached genome-wide significance (p <
      5.0 * 10(-8)). However, investigations into nominal observed SNP associations (p
      < 1.0 * 10(-5)) add support to two positional candidate genes previously
      implicated in ASD etiology, PRKCB1, and CBLN1. The rs198198 SNP (p = 9.587 * 10(
      6)), is located within an intron of the protein kinase C, beta 1 (PRKCB1) gene on
      chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and
      association studies for ASD, and its mRNA expression has been shown to be
      significantly down regulated in ASD cases compared with controls. The rs16946931
      SNP (p = 1.78 * 10(-6)) is located in a region flanking the Cerebellin 1 (CBLN1)
      gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is
      part of a gene family previously implicated in ASD. This GWA study is only the
      second to examine SNPs associated with autistic-like traits in the general
      population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes
      in risk of clinical ASD. 

PMID- 24133441
TI  - Functional opposition between habenula metabolism and the brain reward system.

PMID- 24133440
TI  - Vestibular modulation of spatial perception.
AB  - Vestibular inputs make a key contribution to the sense of one's own spatial
      location. While the effects of vestibular stimulation on visuo-spatial processing
      in neurological patients have been extensively described, the normal contribution
      of vestibular inputs to spatial perception remains unclear. To address this
      issue, we used a line bisection task to investigate the effects of galvanic
      vestibular stimulation (GVS) on spatial perception, and on the transition between
      near and far space. Brief left-anodal and right-cathodal GVS or right-anodal and
      left-cathodal GVS were delivered. A sham stimulation condition was also included.
      Participants bisected lines of different lengths at six distances from the body
      using a laser pointer. Consistent with previous results, our data showed an
      overall shift in the bisection bias from left to right as viewing distance
      increased. This pattern suggests leftward bias in near space, and rightward bias
      in far space. GVS induced strong polarity dependent effects in spatial
      perception, broadly consistent with those previously reported in patients: left
      anodal and right-cathodal GVS induced a leftward bisection bias, while right
      anodal and left-cathodal GVS reversed this effect, and produced bisection bias
      toward the right side of the space. Interestingly, the effects of GVS were
      comparable in near and far space. We speculate that vestibular-induced biases in
      space perception may optimize gathering of information from different parts of
      the environment. 

PMID- 24133442
TI  - Covert oculo-manual coupling induced by visually guided saccades.
AB  - Hand pointing to objects under visual guidance is one of the most common motor
      behaviors in everyday life. In natural conditions, gaze and arm movements are
      commonly aimed at the same target and the accuracy of both systems is
      considerably enhanced if eye and hand move together. Evidence supports the
      viewpoint that gaze and limb control systems are not independent but at least
      partially share a common neural controller. The aim of the present study was to
      verify whether a saccade execution induces excitability changes in the upper-limb
      corticospinal system (CSS), even in the absence of a manual response. This effect
      would provide evidence for the existence of a common drive for ocular and arm
      motor systems during fast aiming movements. Single-pulse TMS was applied to the
      left motor cortex of 19 subjects during a task involving visually guided
      saccades, and motor evoked potentials (MEPs) induced in hand and wrist muscles of
      the contralateral relaxed arm were recorded. Subjects had to make visually guided
      saccades to one of 6 positions along the horizontal meridian (+/-5 degrees , +/
      10 degrees , or +/-15 degrees ). During each trial, TMS was randomly delivered at
      one of 3 different time delays: shortly after the end of the saccade or 300 or
      540 ms after saccade onset. Fast eye movements toward a peripheral target were
      accompanied by changes in upper-limb CSS excitability. MEP amplitude was highest
      immediately after the end of the saccade and gradually decreased at longer TMS
      delays. In addition to the change in overall CSS excitability, MEPs were
      specifically modulated in different muscles, depending on the target position and
      the TMS delay. By applying a simple model of a manual pointing movement, we
      demonstrated that the observed changes in CSS excitability are compatible with
      the facilitation of an arm motor program for a movement aimed at the same target
      of the gaze. These results provide evidence in favor of the existence of a common
      drive for both eye and arm motor systems. 

PMID- 24133443
TI  - First evidence of a hyperdirect prefrontal pathway in the primate: precise
      organization for new insights on subthalamic nucleus functions.

PMID- 24133444
TI  - Muscle synergy space: learning model to create an optimal muscle synergy.
AB  - Muscle redundancy allows the central nervous system (CNS) to choose a suitable
      combination of muscles from a number of options. This flexibility in muscle
      combinations allows for efficient behaviors to be generated in daily life. The
      computational mechanism of choosing muscle combinations, however, remains a long
      standing challenge. One effective method of choosing muscle combinations is to
      create a set containing the muscle combinations of only efficient behaviors, and
      then to choose combinations from that set. The notion of muscle synergy, which
      was introduced to divide muscle activations into a lower-dimensional synergy
      space and time-dependent variables, is a suitable tool relevant to the discussion
      of this issue. The synergy space defines the suitable combinations of muscles,
      and time-dependent variables vary in lower-dimensional space to control
      behaviors. In this study, we investigated the mechanism the CNS may use to define
      the appropriate region and size of the synergy space when performing skilled
      behavior. Two indices were introduced in this study, one is the synergy stability
      index (SSI) that indicates the region of the synergy space, the other is the
      synergy coordination index (SCI) that indicates the size of the synergy space.
      The results on automatic posture response experiments show that SSI and SCI are
      positively correlated with the balance skill of the participants, and they are
      tunable by behavior training. These results suggest that the CNS has the ability
      to create optimal sets of efficient behaviors by optimizing the size of the
      synergy space at the appropriate region through interacting with the environment.

PMID- 24133445
TI  - How to assess the reliability of cerebral microbleed rating?

PMID- 24133446
TI  - PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents
      renal injury with reduced risk of hyperkalemia in an animal model of nephropathy.
AB  - The mineralocorticoid receptor (MR) antagonists PF-03882845 and eplerenone were
      evaluated for renal protection against aldosterone-mediated renal disease in
      uninephrectomized Sprague-Dawley (SD) rats maintained on a high salt diet and
      receiving aldosterone by osmotic mini-pump for 27 days. Serum K(+) and the
      urinary albumin to creatinine ratio (UACR) were assessed following 14 and 27 days
      of treatment. Aldosterone induced renal fibrosis as evidenced by increases in
      UACR, collagen IV staining in kidney cortex, and expression of pro-fibrotic genes
      relative to sham-operated controls not receiving aldosterone. While both PF
      03882845 and eplerenone elevated serum K(+) levels with similar potencies, PF
      03882845 was more potent than eplerenone in suppressing the rise in UACR. PF
      03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID
      while eplerenone was effective only at the highest dose tested (450 mg/kg BID).
      All doses of PF-03882845 suppressed aldosterone-induced increases in collagen IV,
      transforming growth factor-beta 1 (Tgf-beta 1), interleukin-6 (Il-6),
      intermolecular adhesion molecule-1 (Icam-1) and osteopontin gene expression in
      kidney while eplerenone was only effective at the highest dose. The therapeutic
      index (TI), calculated as the ratio of the EC50 for increasing serum K(+) to the
      EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. Thus,
      the TI of PF-03882845 against hyperkalemia was 57-fold superior to that of
      eplerenone indicating that PF-03882845 may present significantly less risk for
      hyperkalemia compared to eplerenone. 

PMID- 24133448
TI  - A method for biomarker measurements in peripheral blood mononuclear cells
      isolated from anxious and depressed mice: beta-arrestin 1 protein levels in
      depression and treatment.
AB  - A limited number of biomarkers in the central and peripheral systems which are
      known may be useful for diagnosing major depressive disorders and predicting the
      effectiveness of antidepressant (AD) treatments. Since 60% of depressed patients
      do not respond adequately to medication or are resistant to ADs, it is imperative
      to delineate more accurate biomarkers. Recent clinical studies suggest that beta
      arrestin 1 levels in human mononuclear leukocytes may be an efficient biomarker.
      If potential biomarkers such as beta-arrestin 1 could be assessed from a source
      such as peripheral blood cells, then they could be easily monitored and used to
      predict therapeutic responses. However, no previous studies have measured beta
      arrestin 1 levels in peripheral blood mononuclear cells (PBMCs) in
      anxious/depressive rodents. This study aimed to develop a method to detect beta
      arrestin protein levels through immunoblot analyses of mouse PBMCs isolated from
      whole blood. In order to validate the approach, beta-arrestin levels were then
      compared in na?"{?i}ve, anxious/depressed mice, and anxious/depressed mice
      treated with a selective serotonin reuptake inhibitor (fluoxetine, 18~mg/kg/day
      in the drinking water). The results demonstrated that mouse whole blood collected
      by submandibular bleeding permitted isolation of enough PBMCs to assess
      circulating proteins such as beta-arrestin 1. beta-Arrestin 1 levels were
      successfully measured in healthy human subject and na?"{?i}ve mouse PBMCs.
      Interestingly, PBMCs from anxious/depressed mice showed significantly reduced
      beta-arrestin 1 levels. These decreased beta-arrestin 1 expression levels were
      restored to normal levels with chronic fluoxetine treatment. The results suggest
      that isolation of PBMCs from mice by submandibular bleeding is a useful technique
      to screen putative biomarkers of the pathophysiology of mood disorders and the
      response to ADs. In addition, these results confirm that beta-arrestin 1 is a
      potential biomarker for depression. 

PMID- 24133447
TI  - Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy
      of the central nervous system?
AB  - The coordination of tissue function is mediated by gap junctions (GJs) that
      enable direct cell-cell transfer of metabolic and electric signals. GJs are
      formed by connexins of which Cx43 is most widespread in the human body. In the
      brain, Cx43 GJs are mostly found in astroglia where they coordinate the
      propagation of Ca(2+) waves, spatial K(+) buffering, and distribution of glucose.
      Beyond its role in direct intercellular communication, Cx43 also forms unapposed,
      non-junctional hemichannels in the plasma membrane of glial cells. These allow
      the passage of several neuro- and gliotransmitters that may, combined with
      downstream paracrine signaling, complement direct GJ communication among glial
      cells and sustain glial-neuronal signaling. Mutations in the GJA1 gene encoding
      Cx43 have been identified in a rare, mostly autosomal dominant syndrome called
      oculodentodigital dysplasia (ODDD). ODDD patients display a pleiotropic phenotype
      reflected by eye, hand, teeth, and foot abnormalities, as well as craniofacial
      and bone malformations. Remarkably, neurological symptoms such as dysarthria,
      neurogenic bladder (manifested as urinary incontinence), spasticity or muscle
      weakness, ataxia, and epilepsy are other prominent features observed in ODDD
      patients. Over 10 mutations detected in patients diagnosed with neurological
      disorders are associated with altered functionality of Cx43 GJs/hemichannels, but
      the link between ODDD-related abnormal channel activities and neurologic
      phenotype is still elusive. Here, we present an overview on the nature of the
      mutants conveying structural and functional changes of Cx43 channels and discuss
      available evidence for aberrant Cx43 GJ and hemichannel function. In a final
      step, we examine the possibilities of how channel dysfunction may lead to some of
      the neurological manifestations of ODDD. 

PMID- 24133449
TI  - Role of liver progenitors in acute liver injury.
AB  - Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte
      function and frequently exhibits a fulminant course, characterized by high
      mortality in the absence of immediate state-of-the-art intensive care and/or
      emergency liver transplantation (ELT). The role of hepatocyte-mediated liver
      regeneration during acute and chronic liver injury has been extensively
      investigated, and recent studies suggest that hepatocytes are not exclusively
      responsible for the regeneration of the injured liver during fulminant liver
      injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent
      in the healthy liver, but may be activated under conditions where the
      regenerative capacity of mature hepatocytes is severely impaired. This review
      aims to provide an overview of the role of the LPC population during ALF, and the
      role of putative cytokines, growth factors, mitogens, and hormones in the LPC
      response. We will highlight the potential interaction among cellular compartments
      during ALF, and discuss the possible prognostic value of the LPC response on ALF
      outcomes. 

PMID- 24133450
TI  - Mechanisms regulating nutrition-dependent developmental plasticity through organ
      specific effects in insects.
AB  - Nutrition, via the insulin/insulin-like growth factor (IIS)/Target of Rapamycin
      (TOR) signaling pathway, can provide a strong molding force for determining
      animal size and shape. For instance, nutrition induces a disproportionate
      increase in the size of male horns in dung and rhinoceros beetles, or mandibles
      in staghorn or horned flour beetles, relative to body size. In these species,
      well-fed male larvae produce adults with greatly enlarged horns or mandibles,
      whereas males that are starved or poorly fed as larvae bear much more modest
      appendages. Changes in IIS/TOR signaling plays a key role in appendage
      development by regulating growth in the horn and mandible primordia. In contrast,
      changes in the IIS/TOR pathway produce minimal effects on the size of other adult
      structures, such as the male genitalia in fruit flies and dung beetles. The horn,
      mandible and genitalia illustrate that although all tissues are exposed to the
      same hormonal environment within the larval body, the extent to which insulin can
      induce growth is organ specific. In addition, the IIS/TOR pathway affects body
      size and shape by controlling production of metamorphic hormones important for
      regulating developmental timing, like the steroid molting hormone ecdysone and
      sesquiterpenoid hormone juvenile hormone. In this review, we discuss recent
      results from Drosophila and other insects that highlight mechanisms allowing
      tissues to differ in their sensitivity to IIS/TOR and the potential consequences
      of these differences on body size and shape. 

PMID- 24133451
TI  - Targeting cardiac beta-adrenergic signaling via GRK2 inhibition for heart failure
      therapy.
AB  - Cardiac cells, like those of the other tissues, undergo regulation through
      membrane-bound proteins known as G protein-coupled receptors (GPCRs). beta
      adrenergic receptors (betaARs) are key GPCRs expressed on cardiomyocytes and
      their role is crucial in cardiac physiology since they regulate inotropic and
      chronotropic responses of the sympathetic nervous system (SNS). In compromised
      conditions such as heart failure (HF), chronic betaAR hyperstimulation occurs via
      SNS activation resulting in receptor dysregulation and down-regulation and
      consequently there is a marked reduction of myocardial inotropic reserve and
      continued loss of pump function. Data accumulated over the last two decades
      indicates that a primary culprit in initiating and maintain betaAR dysfunction in
      the injured and stressed heart is GPCR kinase 2 (GRK2), which was originally
      known as betaARK1 (for betaAR kinase). GRK2 is up-regulated in the failing heart
      due to chronic SNS activity and targeting this kinase has emerged as a novel
      therapeutic strategy in HF. Indeed, its inhibition or genetic deletion in several
      disparate animal models of HF including a pre-clinical pig model has shown that
      GRK2 targeting improves functional and morphological parameters of the failing
      heart. Moreover, non-betaAR properties of GRK2 appear to also contribute to its
      pathological effects and thus, its inhibition will likely complement existing
      therapies such as betaAR blockade. This review will explore recent research
      regarding GRK2 inhibition; in particular it will focus on the GRK2 inhibitor
      peptide known as betaARKct, which represents new hope in the treatment against HF
      progression. 

PMID- 24133452
TI  - Emerging roles of mitochondria in the evolution, biogenesis, and function of
      peroxisomes.
AB  - In the last century peroxisomes were thought to have an endosymbiotic origin.
      Along with mitochondria and chloroplasts, peroxisomes primarily regulate their
      numbers through the growth and division of pre-existing organelles, and they
      house specific machinery for protein import. These features were considered
      unique to endosymbiotic organelles, prompting the idea that peroxisomes were key
      cellular elements that helped facilitate the evolution of multicellular
      organisms. The functional similarities to mitochondria within mammalian systems
      expanded these ideas, as both organelles scavenge peroxide and reactive oxygen
      species, both organelles oxidize fatty acids, and at least in higher eukaryotes,
      the biogenesis of both organelles is controlled by common nuclear transcription
      factors of the PPAR family. Over the last decade it has been demonstrated that
      the fission machinery of both organelles is also shared, and that both organelles
      act as critical signaling platforms for innate immunity and other pathways. Taken
      together it is clear that the mitochondria and peroxisomes are functionally
      coupled, regulating cellular metabolism and signaling through a number of common
      mechanisms. However, recent work has focused primarily on the role of the ER in
      the biogenesis of peroxisomes, potentially overshadowing the critical importance
      of the mitochondria as a functional partner. In this review, we explore the
      mechanisms of functional coupling of the peroxisomes to the mitochondria/ER
      networks, providing some new perspectives on the potential contribution of the
      mitochondria to peroxisomal biogenesis. 

PMID- 24133453
TI  - Cytoplasmic expression of LGR5 in pancreatic adenocarcinoma.
AB  - BACKGROUND: CD133 has been identified as a cancer stem cell marker for pancreatic
      ductal adenocarcinoma. Although leucine-rich-repeat-containing G-protein-coupled
      receptor 5 (LGR5), a marker of intestinal stem cells, has been shown to be on a
      higher level of the stem cell hierarchy than CD133, the expression and function
      of LGR5 in pancreatic cancer tissue remains unclear. This study investigated
      tissue expression of LGR5 and CD133 in resected pancreatic cancer tissue.
      METHODS: LGR5 and CD133 expression was immunohistochemically examined in 9
      patients with pancreatic ductal adenocarcinoma who underwent resection. RESULTS:
      LGR5 was expressed in the cytoplasm of pancreatic cancer cells in 4 of 9 cases.
      CD133 was not detected in cancerous tissue. In non-neoplastic tissue, LGR5 was
      expressed in the basolateral membrane of a subset of endocrine cells. Conversely,
      CD133 was expressed in the apical membrane of small duct cells. Co-localization
      of LGR5 and CD133 was not found in either neoplastic or non-neoplastic tissue.
      LGR5 expression in pancreatic cancer cells showed no statistically significant
      correlation with survival after surgery. CONCLUSION: We have demonstrated that
      LGR5 is expressed in the cytoplasm of pancreatic adenocarcinoma cells, and the
      basolateral membrane of a subset of endocrine cells of the human pancreas.
      Further investigation is required to clarify any prognostic significance of LGR5
      expression.

PMID- 24133454
TI  - Methods and approaches in the topology-based analysis of biological pathways.
AB  - The goal of pathway analysis is to identify the pathways significantly impacted
      in a given phenotype. Many current methods are based on algorithms that consider
      pathways as simple gene lists, dramatically under-utilizing the knowledge that
      such pathways are meant to capture. During the past few years, a plethora of
      methods claiming to incorporate various aspects of the pathway topology have been
      proposed. These topology-based methods, sometimes referred to as "third
      generation," have the potential to better model the phenomena described by
      pathways. Although there is now a large variety of approaches used for this
      purpose, no review is currently available to offer guidance for potential users
      and developers. This review covers 22 such topology-based pathway analysis
      methods published in the last decade. We compare these methods based on: type of
      pathways analyzed (e.g., signaling or metabolic), input (subset of genes, all
      genes, fold changes, gene p-values, etc.), mathematical models, pathway scoring
      approaches, output (one or more pathway scores, p-values, etc.) and
      implementation (web-based, standalone, etc.). We identify and discuss challenges,
      arising both in methodology and in pathway representation, including inconsistent
      terminology, different data formats, lack of meaningful benchmarks, and the lack
      of tissue and condition specificity. 

PMID- 24133456
TI  - Transport metabolons with carbonic anhydrases.

PMID- 24133455
TI  - The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer.
AB  - Voltage-dependent K(+) channels (Kv) are involved in a number of physiological
      processes, including immunomodulation, cell volume regulation, apoptosis as well
      as differentiation. Some Kv channels participate in the proliferation and
      migration of normal and tumor cells, contributing to metastasis. Altered
      expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors
      and cancer cells. In general, while the expression of Kv1.3 apparently exhibits
      no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues.
      Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation
      with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and
      Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3
      and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas.
      Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may
      indicate their role in tumor growth and their importance as potential tumor
      markers. However, despite of this increasing body of information, which considers
      Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed
      to reach any conclusion. In this review, we summarize what it has been lately
      documented about Kv1.3 and Kv1.5 channels in human cancer. 

PMID- 24133457
TI  - Epigenomic Mechanisms of Early Adversity and HPA Dysfunction: Considerations for
      PTSD Research.
AB  - Childhood adversity can have life-long consequences for the response to stressful
      events later in life. Abuse or severe neglect are well-known risk factors for
      post-traumatic stress disorder (PTSD), at least in part via changes in neural
      systems mediating the endocrine response to stress. Determining the biological
      signatures of risk for stress-related mental disorders such as PTSD is important
      for identifying homogenous subgroups and improving treatment options. This review
      will focus on epigenetic regulation in early life by adversity and parental care 
      prime mediators of offspring neurodevelopment - in order to address several
      questions: (1) what have studies of humans and analogous animal models taught us
      about molecular mechanisms underlying changes in stress-sensitive physiological
      systems in response to early life trauma? (2) What are the considerations for
      studies relating early adversity and PTSD risk, going forward? I will summarize
      studies in animals and humans that address the epigenetic response to early
      adversity in the brain and in peripheral tissues. In so doing, I will describe
      work on the glucocorticoid receptor and other well-characterized genes within the
      stress response pathway and then turn to genomic studies to illustrate the use of
      increasingly powerful high-throughput approaches to the study of epigenomic
      mechanisms. 

PMID- 24133458
TI  - The Association between Cannabis Use, Mental Illness, and Suicidal Behavior: What
      is the Role of Hopelessness?

PMID- 24133459
TI  - Frequency and neural correlates of pauses in patients with formal thought
      disorder.
AB  - BACKGROUND: Pauses during speech may reflect the planning and monitoring of
      discourse, two processes putatively impaired in patients with schizophrenia,
      particularly those with formal thought disorder (FTD). We used functional MRI to
      examine the neural correlates of between-clause and of filled pauses, which are
      respectively associated with speech planning and speech monitoring. METHODS: BOLD
      contrast was measured while six schizophrenia patients with FTD and six healthy
      subjects spoke about Rorshach inkblots. In an event-related design, we examined
      activity associated with pauses that occurred between clauses and with pauses
      that were filled. RESULTS: There was no significant group difference in the
      frequency of between-clause pauses but patients with FTD made strikingly fewer
      filled pauses than controls. Between-clause pauses were associated with
      activation in the anterior part of the left superior temporal gyrus (STG) and the
      left insula in controls and the engagement of these regions was significantly
      attenuated in patients. CONCLUSION: The anterior part of the left STG and the
      left insula are normally involved in both the planning and monitoring of
      discourse. The attenuated engagement of these regions with between-clause pauses
      and the striking infrequency of filled pauses in the patients are consistent with
      cognitive models implicating defective speech planning and speech monitoring in
      schizophrenia, especially in relation to FTD.

PMID- 24133461
TI  - Cannabis Use during Adolescent Development: Susceptibility to Psychiatric
      Illness.
AB  - Cannabis use is increasingly pervasive among adolescents today, even more common
      than cigarette smoking. The evolving policy surrounding the legalization of
      cannabis reaffirms the need to understand the relationship between cannabis
      exposure early in life and psychiatric illnesses. cannabis contains psychoactive
      components, notably Delta(9)-tetrahydrocannabinol (THC), that interfere with the
      brain's endogenous endocannabinoid system, which is critically involved in both
      pre- and post-natal neurodevelopment. Consequently, THC and related compounds
      could potentially usurp normal adolescent neurodevelopment, shifting the brain's
      developmental trajectory toward a disease-vulnerable state, predisposing early
      cannabis users to motivational, affective, and psychotic disorders. Numerous
      human studies, including prospective longitudinal studies, demonstrate that early
      cannabis use is associated with major depressive disorder and drug addiction. A
      strong association between schizophrenia and cannabis use is also apparent,
      especially when considering genetic factors that interact with this environmental
      exposure. These human studies set a foundation for carefully controlled animal
      studies which demonstrate similar patterns following early cannabinoid exposure.
      Given the vulnerable nature of adolescent neurodevelopment and the persistent
      changes that follow early cannabis exposure, the experimental findings outlined
      should be carefully considered by policymakers. In order to fully address the
      growing issues of psychiatric illnesses and to ensure a healthy future, measures
      should be taken to reduce cannabis use among teens. 

PMID- 24133460
TI  - Pathways from cannabis to psychosis: a review of the evidence.
AB  - The nature of the relationship between cannabis use (CU) and psychosis is complex
      and remains unclear. Researchers and clinicians remain divided regarding key
      issues such as whether or not cannabis is an independent cause of psychosis and
      schizophrenia. This paper reviews the field in detail, examining questions of
      causality, the neurobiological basis for such causality and for differential
      inter-individual risk, the clinical and cognitive features of psychosis in
      cannabis users, and patterns of course and outcome of psychosis in the context of
      CU. The author proposes two major pathways from cannabis to psychosis based on a
      differentiation between early-initiated lifelong CU and a scenario where
      vulnerable individuals without a lifelong pattern of use consume cannabis over a
      relatively brief period of time just prior to psychosis onset. Additional key
      factors determining the clinical and neurobiological manifestation of psychosis
      as well as course and outcome in cannabis users include: underlying genetic and
      developmental vulnerability to schizophrenia-spectrum disorders; and whether or
      not CU ceases or continues after the onset of psychosis. Finally, methodological
      guidelines are presented for future research aimed at both elucidating the
      pathways that lead from cannabis to psychosis and clarifying the long-term
      outcome of the disorder in those who have a history of using cannabis. 

PMID- 24133462
TI  - Functional Neuroimaging Correlates of Burnout among Internal Medicine Residents
      and Faculty Members.
AB  - Burnout is prevalent in residency training and practice and is linked to medical
      error and suboptimal patient care. However, little is known about how burnout
      affects clinical reasoning, which is essential to safe and effective care. The
      aim of this study was to examine how burnout modulates brain activity during
      clinical reasoning in physicians. Using functional Magnetic Resonance Imaging
      (fMRI), brain activity was assessed in internal medicine residents (n = 10) and
      board-certified internists (faculty, n = 17) from the Uniformed Services
      University (USUHS) while they answered and reflected upon United States Medical
      Licensing Examination and American Board of Internal Medicine multiple-choice
      questions. Participants also completed a validated two-item burnout scale, which
      includes an item assessing emotional exhaustion and an item assessing
      depersonalization. Whole brain covariate analysis was used to examine blood
      oxygen-level-dependent (BOLD) signal during answering and reflecting upon
      clinical problems with respect to burnout scores. Higher depersonalization scores
      were associated with less BOLD signal in the right dorsolateral prefrontal cortex
      and middle frontal gyrus during reflecting on clinical problems and less BOLD
      signal in the bilateral precuneus while answering clinical problems in residents.
      Higher emotional exhaustion scores were associated with more right posterior
      cingulate cortex and middle frontal gyrus BOLD signal in residents. Examination
      of faculty revealed no significant influence of burnout on brain activity.
      Residents appear to be more susceptible to burnout effects on clinical reasoning,
      which may indicate that residents may need both cognitive and emotional support
      to improve quality of life and to optimize performance and learning. These
      results inform our understanding of mental stress, cognitive control as well as
      cognitive load theory. 

PMID- 24133463
TI  - Cox's Chair Revisited: Can Spinning Alter Mood States?
AB  - Although there is clinical and historical evidence for a vivid relation between
      the vestibular and emotional systems, the neuroscientific underpinnings are
      poorly understood. The "spin doctors" of the nineteenth century used spinning
      chairs (e.g., Cox's chair) to treat conditions of mania or elevated arousal. On
      the basis of a recent study on a hexapod motion-simulator, in this prototypic
      investigation we explore the impact of yaw stimulation on a spinning chair on
      mood states. Using a controlled experimental stimulation paradigm on a unique 3-D
      turntable at the University of Zurich we included 11 healthy subjects and
      assessed parameters of mood states and autonomic nervous system activity. The
      Multidimensional Mood State Questionnaire and Visual Analog Scales (VAS) were
      used to assess changes of mood in response to a 100 s yaw stimulation. In
      addition heart rate was continuously monitored during the experiment. Subjects
      indicated feeling less "good," "relaxed," "comfortable," and "calm" and reported
      an increased alertness after vestibular stimulation. However, there were no
      objective adverse effects of the stimulation. Accordingly, heart rate did not
      significantly differ in response to the stimulation. This is the first study in a
      highly controlled setting using the historical approach of stimulating the
      vestibular system to impact mood states. It demonstrates a specific interaction
      between the vestibular system and mood states and thereby supports recent
      experimental findings with a different stimulation technique. These results may
      inspire future research on the clinical potential of this method. 

PMID- 24133464
TI  - Gene x environment interactions in schizophrenia and bipolar disorder: evidence
      from neuroimaging.
AB  - INTRODUCTION: Schizophrenia (SZ) and Bipolar disorder (BD) are considered as
      severe multifactorial diseases, stemming from genetic and environmental
      influences. Growing evidence supports gene x environment (GxE) interactions in
      these disorders and neuroimaging studies can help us to understand how those
      factors mechanistically interact. No reviews synthesized the existing data of
      neuroimaging studies in these issues. METHODS: We conduct a systematic review on
      the neuroimaging studies exploring GxE interactions relative to SZ or BD in
      PubMed. RESULTS: First results of the influence of genetic and environmental
      risks on brain structures came from monozygotic twin pairs concordant and
      discordant for SZ or BD. Few structural magnetic resonance imaging (sMRI) studies
      have explored the GxE interactions. No other imaging methods were found. Two main
      GxE interactions on brain volumes have arisen. First, an interaction between
      genetic liability to SZ and obstetric complications on gray matter, cerebrospinal
      fluid, and hippocampal volumes. Second, cannabis use and genetic liability
      interaction effects on cortical thickness and white matter volumes. CONCLUSION:
      Combining GxE interactions and neuroimaging domains is a promising approach.
      Genetic risk and environmental exposures such as cannabis or obstetrical
      complications seem to interact leading to specific neuroimaging cerebral
      alterations in SZ. They are suggestive of GxE interactions that confer phenotypic
      abnormalities in SZ and possibly BD. We need further, larger neuroimaging studies
      of GxE interactions for which we may propose a framework focusing on GxE
      interactions data already known to have a clinical effect such as infections,
      early stress, urbanicity, and substance abuse.

PMID- 24133466
TI  - Honesty requires time-a reply to Foerster et al. (2013).

PMID- 24133465
TI  - Environmental influences on neural systems of relational complexity.
AB  - Constructivist learning theory contends that we construct knowledge by experience
      and that environmental context influences learning. To explore this principle, we
      examined the cognitive process relational complexity (RC), defined as the number
      of visual dimensions considered during problem solving on a matrix reasoning task
      and a well-documented measure of mature reasoning capacity. We sought to
      determine how the visual environment influences RC by examining the influence of
      color and visual contrast on RC in a neuroimaging task. To specify the
      contributions of sensory demand and relational integration to reasoning, our
      participants performed a non-verbal matrix task comprised of color, no-color
      line, or black-white visual contrast conditions parametrically varied by
      complexity (relations 0, 1, 2). The use of matrix reasoning is ecologically valid
      for its psychometric relevance and for its potential to link the processing of
      psychophysically specific visual properties with various levels of RC during
      reasoning. The role of these elements is important because matrix tests assess
      intellectual aptitude based on these seemingly context-less exercises. This
      experiment is a first step toward examining the psychophysical underpinnings of
      performance on these types of problems. The importance of this is increased in
      light of recent evidence that intelligence can be linked to visual
      discrimination. We submit three main findings. First, color and black-white
      visual contrast (BWVC) add demand at a basic sensory level, but contributions
      from color and from BWVC are dissociable in cortex such that color engages a
      "reasoning heuristic" and BWVC engages a "sensory heuristic." Second, color
      supports contextual sense-making by boosting salience resulting in faster problem
      solving. Lastly, when visual complexity reaches 2-relations, color and visual
      contrast relinquish salience to other dimensions of problem solving. 

PMID- 24133467
TI  - Synesthesia, at and near its borders.

PMID- 24133468
TI  - Training, hypnosis, and drugs: artificial synaesthesia, or artificial paradises?
AB  - The last few years have seen the publication of a number of studies by
      researchers claiming to have induced "synaesthesia," "pseudo-synaesthesia," or
      "synaesthesia-like" phenomena in non-synaesthetic participants. Although the
      intention of these studies has been to try and shed light on the way in which
      synaesthesia might have been acquired in developmental synaesthestes, we argue
      that they may only have documented a phenomenon that has elsewhere been accounted
      for in terms of the acquisition of sensory associations and is not evidently
      linked to synaesthesia. As synaesthesia remains largely defined in terms of the
      involuntary elicitation of conscious concurrents, we suggest that the theoretical
      rapprochement with synaesthesia (in any of its guises) is unnecessary, and
      potentially distracting. It might therefore, be less confusing if researchers
      were to avoid referring to synaesthesia when characterizing cases that lack
      robust evidence of a conscious manifestation. Even in the case of those other
      conditions for which conscious experiences are better evidenced, when training
      has been occurred during hypnotic suggestion, or when it has been combined with
      drugs, we argue that not every conscious manifestation should necessarily be
      counted as synaesthetic. Finally, we stress that cases of associative learning
      are unlikely to shed light on two highly specific characteristic of the majority
      of cases of developmental synaesthesia in terms of learning patterns: First,
      their resistance to change through exposure once the synaesthetic repertoire has
      been fixed; Second, the transfer of conditioned responses between concurrents and
      inducers after training. We conclude by questioning whether, in adulthood, it is
      ever possible to acquire the kind of synaesthesia that is typically documented in
      the developmental form of the condition. The available evidence instead seems to
      point to there being a critical period for the development of synaesthesia,
      probably only in those with a genetic predisposition to develop the condition. 

PMID- 24133470
TI  - Dreaming and the neurobiology of self: recent advances and implications for
      psychiatry.

PMID- 24133469
TI  - Sensitive and critical periods in visual sensory deprivation.
AB  - While the demonstration of crossmodal plasticity is well established in
      congenital and early blind individuals, great debate still surrounds whether
      those who acquire blindness later in life can also benefit from such compensatory
      changes. No proper consensus has been reached despite the fact that a proper
      understanding of the developmental time course of these changes, and whether
      their occurrence is limited to-or within-specific time windows, is crucial to our
      understanding of the crossmodal phenomena. An extensive review of the literature
      reveals that while the majority of investigations to date have examined the
      crossmodal plasticity available to late blind individuals in quantitative terms,
      recent findings rather suggest that this reorganization also likely changes
      qualitatively compared to what is observed in early blindness. This obviously
      could have significant repercussions not only for the training and rehabilitation
      of blind individuals, but for the development of appropriate neuroprostheses
      designed to aid and potentially restore vision. Important parallels will also be
      drawn with the current state of research on deafness, which is particularly
      relevant given in the development of successful neuroprostheses (e.g., cochlear
      implants) for providing auditory input to the central nervous system otherwise
      aurally deafferented. Lastly, this paper will address important inconsistencies
      across the literature concerning the definition of distinct blind groups based on
      the age of blindness onset, and propose several alternatives to using such a
      categorization. 

PMID- 24133471
TI  - A componential view of children's difficulties in learning fractions.
AB  - Fractions are well known to be difficult to learn. Various hypotheses have been
      proposed in order to explain those difficulties: fractions can denote different
      concepts; their understanding requires a conceptual reorganization with regard to
      natural numbers; and using fractions involves the articulation of conceptual
      knowledge with complex manipulation of procedures. In order to encompass the
      major aspects of knowledge about fractions, we propose to distinguish between
      conceptual and procedural knowledge. We designed a test aimed at assessing the
      main components of fraction knowledge. The test was carried out by fourth-, fifth
      and sixth-graders from the French Community of Belgium. The results showed large
      differences between categories. Pupils seemed to master the part-whole concept,
      whereas numbers and operations posed problems. Moreover, pupils seemed to apply
      procedures they do not fully understand. Our results offer further directions to
      explain why fractions are amongst the most difficult mathematical topics in
      primary education. This study offers a number of recommendations on how to teach
      fractions. 

PMID- 24133473
TI  - Further evidence for the interaction of central and peripheral processes: the
      impact of double letters in writing English words.
AB  - Most studies on spelling processes suppose that the activation of orthographic
      representations is over before we start to write. The goal of the present study
      was to provide evidence indicating that the orthographic representations
      activated during spelling production interact continuously with the motor
      processes during movement production. We manipulated gemination to assess the
      influence of the orthographic properties of words on the kinematic parameters of
      production. Native English-speaking participants wrote words containing double
      letters and control words on a digitizer [e.g., DISSIPATE (Geminate) and DISGRACE
      (Control)]. The word pairs shared the initial letters and differed on the
      presence of a doublet at the same position. The results revealed that latencies
      were shorter for Geminates than Controls, indicating that spelling processes were
      facilitated by the presence of a doublet in the word. Critically, the impact of
      letter doubling was also observed during production, with shorter letter
      durations (e.g., D, I, S) and intervals (DI, IS) for Geminates than Controls.
      Letter doubling therefore affected the whole process of word writing: from
      spelling recall to movement preparation and production. The spelling processes
      that were involved before movement initiation cascaded into processes that
      regulate movement execution. The activation spread onto peripheral processing
      until the production of the doublet was completely programmed (e.g., letter S). 

PMID- 24133472
TI  - The neurocognitive consequences of the wandering mind: a mechanistic account of
      sensory-motor decoupling.
AB  - A unique human characteristic is our ability to mind wander - a state in which we
      are free to engage in thoughts that are not directly tied to sensations and
      perceptions from our immediate physical environment. From a neurocognitive
      perspective, it has been proposed that during mind wandering, our executive
      resources are decoupled from the external environment and directed to these
      internal thoughts. In this review, we examine an underappreciated aspect of this
      phenomenon - attenuation of sensory-motor processing - from two perspectives.
      First, we describe the range of widespread sensory, cognitive and motor processes
      attenuated during mind wandering states, and how this impacts our neurocognitive
      processing of external events. We then consider sensory-motor attenuation in a
      class of clinical neurocognitive disorders that have ties to pathological
      patterns of decoupling, reviews suggesting that mind wandering and these clinical
      states may share a common mechanism of sensory-motor attenuation. Taken together,
      these observations suggest the sensory-motor consequences of decoupled thinking
      are integral to normal and pathological neurocognitive states. 

PMID- 24133474
TI  - The Iowa Gambling Task in depression - what have we learned about sub-optimal
      decision-making strategies?
AB  - Our earlier study found patients with depression to show a preference for larger
      reward as measured by the Iowa Gambling Task (IGT). In this IGT version, larger
      rewards were associated with even larger consequent losses. In the light of the
      clinical markers defining depressive disorder, this finding might appear
      controversial at first. Performance of depressed patients on various decision
      making (DM) tasks is typically found to be impaired. Evidence points toward
      reduced reward learning, as well as the difficulty to shift strategy and
      integrate environmental changes into DM contingencies. This results in an
      impaired ability to modulate behavior as a function of reward, or punishment,
      respectively. Clinical symptoms of the disorder, the genetic profile, as well as
      personality traits might also influence DM strategies. More severe depression
      increased sensitivity to immediate large punishment, thus predicting future
      decisions, and was also associated with higher harm avoidance. Anhedonic features
      diminished reward learning abilities to a greater extent, even predicting
      clinical outcome. Several questions about how these aspects relate remain to be
      clarified. Is there a genetic predisposition for the DM impairment preceding mood
      symptoms? Is it the consequence of clinical signs or even learned behavior
      serving as a coping strategy? Are patients prone to develop an aversion of loss
      or are they unable to sense or deal with reward or the preference of reward? Does
      the DM deficit normalize or is a persisting impairment predictor for clinical
      outcome or relapse risk? To what extent is it influenced by medication effects?
      How does a long-lasting DM deficit affect daily life and social interactions?
      Strikingly, research evidence indicates that depressed patients tend to behave
      less deceptive and more self-focused, resulting in impaired social DM. The
      difficulty in daily interpersonal interactions might contribute to social
      isolation, further intensifying depressive symptoms. 

PMID- 24133475
TI  - Acoustic cues for the recognition of self-voice and other-voice.
AB  - Self-recognition, being indispensable for successful social communication, has
      become a major focus in current social neuroscience. The physical aspects of the
      self are most typically manifested in the face and voice. Compared with the
      wealth of studies on self-face recognition, self-voice recognition (SVR) has not
      gained much attention. Converging evidence has suggested that the fundamental
      frequency (F0) and formant structures serve as the key acoustic cues for other
      voice recognition (OVR). However, little is known about which, and how, acoustic
      cues are utilized for SVR as opposed to OVR. To address this question, we
      independently manipulated the F0 and formant information of recorded voices and
      investigated their contributions to SVR and OVR. Japanese participants were
      presented with recorded vocal stimuli and were asked to identify the speaker
      either themselves or one of their peers. Six groups of 5 peers of the same sex
      participated in the study. Under conditions where the formant information was
      fully preserved and where only the frequencies lower than the third formant (F3)
      were retained, accuracies of SVR deteriorated significantly with the modulation
      of the F0, and the results were comparable for OVR. By contrast, under a
      condition where only the frequencies higher than F3 were retained, the accuracy
      of SVR was significantly higher than that of OVR throughout the range of F0
      modulations, and the F0 scarcely affected the accuracies of SVR and OVR. Our
      results indicate that while both F0 and formant information are involved in SVR,
      as well as in OVR, the advantage of SVR is manifested only when major formant
      information for speech intelligibility is absent. These findings imply the
      robustness of self-voice representation, possibly by virtue of auditory
      familiarity and other factors such as its association with motor/articulatory
      representation. 

PMID- 24133476
TI  - On the interrelation of multiplication and division in secondary school children.
AB  - MULTIPLICATION AND DIVISION ARE CONCEPTUALLY INVERSELY RELATED: Each division
      problem can be transformed into as a multiplication problem and vice versa.
      Recent research has indicated strong developmental parallels between
      multiplication and division in primary school children. In this study, we were
      interested in (i) whether these developmental parallels persist into secondary
      school, (ii) whether similar developmental parallels can be observed for simple
      and complex problems, (iii) whether skill level modulates this relationship, and
      (iv) whether the correlations are specific and not driven by general cognitive or
      arithmetic abilities. Therefore, we assessed performance of 5th and 6th graders
      attending two secondary school types of the German educational system in simple
      and complex multiplication as well as division while controlling for non-verbal
      intelligence, short-term memory, and other arithmetic abilities. Accordingly, we
      collected data from students differing in skills levels due to either age (5th <
      6th grade) or school type (general < intermediate secondary school). We observed
      moderate to strong bivariate and partial correlations between multiplication and
      division with correlations being higher for simple tasks but nevertheless
      reliable for complex tasks. Moreover, the association between simple
      multiplication and division depended on students' skill levels as reflected by
      school types, but not by age. Partial correlations were higher for intermediate
      than for general secondary school children. In sum, these findings emphasize the
      importance of the inverse relationship between multiplication and division which
      persists into later developmental stages. However, evidence for skill-related
      differences in the relationship between multiplication and division was
      restricted to the differences for school types.

PMID- 24133477
TI  - Who is she? Changes in the person context affect categorization.
AB  - Changes between the learning and testing contexts affect learning, memory, and
      generalization. We examined whether a change (between learning and testing) in
      the person children were interacting with affects generalization. Three-, four-,
      and five-year-old children were trained on eight novel noun categories by one
      experimenter. Children were tested for their ability to generalize the label to a
      new category member by either the same experimenter who trained them or by a
      novel experimenter. Three-year-old children's performance was not affected by who
      they were tested by. Four- and five-year-old children's performance was lower
      when tested by the novel experimenter. The results are discussed in terms of
      source monitoring and the effect of perceptual context change on category
      generalization. 

PMID- 24133478
TI  - Virtual sensory feedback for gait improvement in neurological patients.
AB  - We review a treatment modality for movement disorders by sensory feedback. The
      natural closed-loop sensory-motor feedback system is imitated by a wearable
      virtual reality apparatus, employing body-mounted inertial sensors and responding
      dynamically to the patient's own motion. Clinical trials have shown a significant
      gait improvement in patients with Parkinson's disease using the apparatus. In
      contrast to open-loop devices, which impose constant-velocity visual cues in a
      "treadmill" fashion, or rhythmic auditory cues in a "metronome" fashion,
      requiring constant vigilance and attention strategies, and, in some cases,
      instigating freezing in Parkinson's patients, the closed-loop device improved
      gait parameters and eliminated freezing in most patients, without side effects.
      Patients with multiple sclerosis, previous stroke, senile gait, and cerebral
      palsy using the device also improved their balance and gait substantially.
      Training with the device has produced a residual improvement, suggesting virtual
      sensory feedback for the treatment of neurological movement disorders. 

PMID- 24133479
TI  - Automated decision-support system for prediction of treatment responders in acute
      ischemic stroke.
AB  - MRI is widely used in the assessment of acute ischemic stroke. In particular, it
      identifies the mismatch between hypoperfused and the permanently damaged tissue,
      the PWI-DWI mismatch volume. It is used to help triage patients into active or
      supportive treatment pathways. COMBAT Stroke is an automated software tool for
      estimating the mismatch volume and ratio based on MRI. Herein, we validate the
      decision made by the software with actual clinical decision rendered.
      Furthermore, we evaluate the association between treatment decisions (both
      automated and actual) and outcomes. COMBAT Stroke was used to determine PWI-DWI
      mismatch volume and ratio in 228 patients from two European multi-center stroke
      databases. We performed confusion matrix analysis to summarize the agreement
      between the automated selection and the clinical decision. Finally, we evaluated
      the clinical and imaging outcomes of the patients in the four entries of the
      confusion matrix (true positive, true negative, false negative, and false
      positive). About 186 of 228 patients with acute stroke underwent thrombolytic
      treatment, with the remaining 42 receiving supportive treatment only. Selection
      based on radiographic criteria using COMBAT Stroke classified 142 patients as
      potential candidates for thrombolytic treatment and 86 for supportive treatment;
      60% sensitivity and 29% specificity. The patients deemed eligible for
      thrombolytic treatment by COMBAT Stroke demonstrated significantly higher rates
      of compromised tissue salvage, less neurological deficit, and were more likely to
      experience thrombus dissolving and reestablishment of normal blood flow at 24 h
      follow-up compared to those who were treated without substantial PWI-DWI
      mismatch. These results provide evidence that COMBAT Stroke, in addition to
      clinical assessment, may offer an optimal framework for a fast, efficient, and
      standardized clinical support tool to select patients for thrombolysis in acute
      ischemic stroke. 

PMID- 24133480
TI  - Complex-value coherence mapping reveals novel abnormal resting-state functional
      connectivity networks in task-specific focal hand dystonia.
AB  - Resting-state imaging designs are powerful in modeling functional networks in
      movement disorders because they eliminate task performance related confounds.
      However, the most common metric for quantifying functional connectivity, i.e.,
      bivariate magnitude coherence (Coh), can sometimes be contaminated by spurious
      correlations in blood-oxygen level dependent (BOLD) signal due to smoothing and
      seed blur, thereby limiting the identification of true interactions between
      neighboring neural populations. Here, we apply a novel functional connectivity
      metric., i.e., imaginary coherence (ICoh), to BOLD fMRI data in healthy
      individuals and patients with task-specific focal hand dystonia (tspFHD), in
      addition to the traditional magnitude Coh metric. We reconstructed resting-state
      sensorimotor, basal ganglia, and default-mode networks using both Coh and ICoh.
      We demonstrate that indeed the ICoh metric eliminates spatial blur around seed
      placement and reflects slightly different networks from Coh. We then identified
      significant reductions in resting-state connectivity within both the sensorimotor
      and basal ganglia networks in patients with tspFHD, primarily in the hemisphere
      contralateral to the affected hand. Collectively, these findings direct our
      attention to the fact that multiple networks are decoupled in tspFHD that can be
      unraveled by different functional connectivity metrics, and that this aberrant
      communication contributes to clinical deficits in the disorder. 

PMID- 24133481
TI  - Primary blast traumatic brain injury in the rat: relating diffusion tensor
      imaging and behavior.
AB  - The incidence of traumatic brain injury (TBI) among military personnel is at its
      highest point in U.S. history. Experimental animal models of blast have provided
      a wealth of insight into blast injury. The mechanisms of neurotrauma caused by
      blast, however, are still under debate. Specifically, it is unclear whether the
      blast shockwave in the absence of head motion is sufficient to induce brain
      trauma. In this study, the consequences of blast injury were investigated in a
      rat model of primary blast TBI. Animals were exposed to blast shockwaves with
      peak reflected overpressures of either 100 or 450 kPa (39 and 110 kPa incident
      pressure, respectively) and subsequently underwent a battery of behavioral tests.
      Diffusion tensor imaging (DTI), a promising method to detect blast injury in
      humans, was performed on fixed brains to detect and visualize the spatial
      dependence of blast injury. Blast TBI caused significant deficits in memory
      function as evidenced by the Morris Water Maze, but limited emotional deficits as
      evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy, a
      metric derived from DTI, revealed significant brain abnormalities in blast
      exposed animals. A significant relationship between memory deficits and brain
      microstructure was evident in the hippocampus, consistent with its role in memory
      function. The results provide fundamental insight into the neurological
      consequences of blast TBI, including the evolution of injury during the sub-acute
      phase and the spatially dependent pattern of injury. The relationship between
      memory dysfunction and microstructural brain abnormalities may provide insight
      into the persistent cognitive difficulties experienced by soldiers exposed to
      blast neurotrauma and may be important to guide therapeutic and rehabilitative
      efforts. 

PMID- 24133482
TI  - Censoring distances based on labeled cortical distance maps in cortical
      morphometry.
AB  - It has been demonstrated that shape differences in cortical structures may be
      manifested in neuropsychiatric disorders. Such morphometric differences can be
      measured by labeled cortical distance mapping (LCDM) which characterizes the
      morphometry of the laminar cortical mantle of cortical structures. LCDM data
      consist of signed/labeled distances of gray matter (GM) voxels with respect to
      GM/white matter (WM) surface. Volumes and other summary measures for each subject
      and the pooled distances can help determine the morphometric differences between
      diagnostic groups, however they do not reveal all the morphometric information
      contained in LCDM distances. To extract more information from LCDM data,
      censoring of the pooled distances is introduced for each diagnostic group where
      the range of LCDM distances is partitioned at a fixed increment size; and at each
      censoring step, the distances not exceeding the censoring distance are kept.
      Censored LCDM distances inherit the advantages of the pooled distances but also
      provide information about the location of morphometric differences which cannot
      be obtained from the pooled distances. However, at each step, the censored
      distances aggregate, which might confound the results. The influence of data
      aggregation is investigated with an extensive Monte Carlo simulation analysis and
      it is demonstrated that this influence is negligible. As an illustrative example,
      GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major
      depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control
      (Ctrl) subjects are used. A significant reduction in laminar thickness of the
      VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the
      GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which
      these differences start to occur are determined. The methodology is also
      applicable to LCDM-based morphometric measures of other cortical structures
      affected by disease. 

PMID- 24133483
TI  - Evaluation of potential protective factors against metabolic syndrome in
      bottlenose dolphins: feeding and activity patterns of dolphins in sarasota bay,
      Florida.
AB  - Free-ranging bottlenose dolphins (Tursiops truncatus) living in Sarasota Bay,
      Florida appear to have a lower risk of developing insulin resistance and
      metabolic syndrome compared to a group of dolphins managed under human care.
      Similar to humans, differences in diet and activity cycles between these groups
      may explain why Sarasota dolphins have lower insulin, glucose, and lipids. To
      identify potential protective factors against metabolic syndrome, existing and
      new data were incorporated to describe feeding and activity patterns of the
      Sarasota Bay wild dolphin community. Sarasota dolphins eat a wide variety of live
      fish and spend 10-20% of daylight hours foraging and feeding. Feeding occurs
      throughout the day, with the dolphins eating small proportions of their total
      daily intake in brief bouts. The natural pattern of wild dolphins is to feed as
      necessary and possible at any time of the day or night. Wild dolphins rarely eat
      dead fish or consume large amounts of prey in concentrated time periods. Wild
      dolphins are active throughout the day and night; they may engage in bouts of
      each key activity category at any time during daytime. Dive patterns of radio
      tagged dolphins varied only slightly with time of day. Travel rates may be
      slightly lower at night, suggesting a diurnal rhythm, albeit not one involving
      complete, extended rest. In comparison, the managed dolphins are older; often fed
      a smaller variety of frozen-thawed fish types; fed fish species not in their
      natural diet; feedings and engaged activities are often during the day; and they
      are fed larger but fewer meals. In summary, potential protective factors against
      metabolic syndrome in dolphins may include young age, activity, and small meals
      fed throughout the day and night, and specific fish nutrients. These protective
      factors against insulin resistance and type 2 diabetes are similar to those
      reported in humans. Further studies may benefit humans and dolphins. 

PMID- 24133484
TI  - Insulin-resistance-associated compensatory mechanisms of pancreatic Beta cells: a
      current opinion.

PMID- 24133485
TI  - De novo Synthesis of Glial Glutamate and Glutamine in Young Mice Requires
      Aspartate Provided by the Neuronal Mitochondrial Aspartate-Glutamate Carrier
      Aralar/AGC1.

PMID- 24133486
TI  - The effects of high-tannin leaf litter from transgenic poplars on microbial
      communities in microcosm soils.
AB  - The impacts of leaf litter from genetically modified hybrid poplar accumulating
      high levels of condensed tannins (proanthocyanidins) were examined in soil
      microcosms consisting of moss growing on sieved soil. Moss preferentially
      proliferated in microcosms with lower tannin content; DGGE (denaturing gradient
      gel electrophoresis) detected increased fungal diversity in microcosms with low
      tannin litter. The proportion of cloned rDNA sequences from Actinobacteria
      decreased with litter addition while Bacteroidetes, Chloroflexi, Cyanobacteria,
      and alpha-Proteobacteria significantly increased. beta-Proteobacteria were
      proportionally more numerous at high-tannin levels. Tannins had no significant
      impact on overall diversity of bacterial communities analyzed with various
      estimators. There was an increased proportion of N-fixing bacteria corresponding
      to the addition of litter with low-tannin levels. The addition of litter
      increased the proportion of Ascomycota/Basidiomycota. Dothideomycetes,
      Pucciniomycetes, and Tremellomycetes also increased and Agaricomycetes decreased.
      Agaricomycetes and Sordariomycetes were significantly more abundant in controls,
      whereas Pucciniomycetes increased in soil with litter from transformed trees (P =
      0.051). Richness estimators and diversity indices revealed no significant
      difference in the composition of fungal communities; PCoA (principal coordinate
      analyses) partitioned the fungal communities into three groups: (i) those with
      higher amounts of added tannin from both transformed and untransformed
      treatments, (ii) those corresponding to soils without litter, and (iii) those
      corresponding to microcosms with litter added from trees transformed only with a
      beta-glucuronidase control vector. While the litter from transformed poplars had
      significant effects on soil microbe communities, the observed impacts reflected
      known impacts on soil processes associated with tannins, and were similar to
      changes that would be expected from natural variation in tannin levels. 

PMID- 24133487
TI  - The bamA gene for anaerobic ring fission is widely distributed in the
      environment.
AB  - Benzoyl-CoA is the signature central metabolite associated with the anaerobic
      metabolism of a diverse range of compounds such as humic acid, lignin, amino
      acids, and industrial chemicals. Aromatic chemicals with different upstream
      degradation pathways all funnel into the downstream benzoyl-CoA pathway.
      Different genes encoding enzymes of the benzoyl-CoA pathway could be used as
      biomarkers for the anaerobic benzoyl-CoA pathway, however, the ring opening
      hydrolase, encoded by the bamA gene, is ideal because it is detected under a
      range of respiratory conditions, including under denitrifying, iron-reducing,
      sulfate-reducing, and fermentative conditions. This work evaluated DNA samples
      from six diverse environments for the presence of the bamA gene, and had positive
      results for every sample. Individual bamA gene clones from these sites were
      compared to published genome sequences. The clone sequences were distributed
      amongst the genome sequences, although there were clone sequences from two of the
      analyzed sites that formed a unique clade. Clone sequences were then grouped by
      site and analyzed with a functional operational taxonomic unit based clustering
      program to compare the bamA gene diversity of these sites to that of several
      locations reported in the literature. The results showed that the sequence
      diversity of the sites separated into two clusters, but there was no clear trend
      that could be related to the site characteristics. Interestingly, two pristine
      freshwater sites formed a subgroup within one of the larger clusters. Thus far
      the bamA gene has only been examined within the context of contaminated
      environments, however, this study demonstrates that the bamA gene is also
      detected in uncontaminated sites. The widespread presence of the bamA gene in
      diverse environments suggests that the anaerobic benzoyl-CoA pathway plays an
      important role in the global carbon cycle that has thus far been understudied. 

PMID- 24133489
TI  - Influenza A(H1N1)pdm09 virus and asthma.
AB  - Respiratory viral infection is a major cause of asthma exacerbations in both
      children and adults. Among the respiratory viruses, influenza virus is a
      particularly important pathogen due to its enormous morbidity and mortality in
      annual epidemics. The swine-origin influenza A virus, designated as A(H1N1)pdm09,
      emerged in the spring of 2009 and caused the first influenza pandemic in the 21st
      century. With the emergence of the novel A(H1N1)pdm09 virus, numerous
      epidemiologic studies detected asthma as a frequent comorbid condition in
      patients infected with this virus. Here we review recent reports regarding asthma
      in patients infected with influenza A(H1N1)pdm09 virus, and we discuss the
      utility of influenza vaccines and antivirals. 

PMID- 24133490
TI  - How numbers, nature, and immune status of foxp3(+) regulatory T-cells shape the
      early immunological events in tumor development.
AB  - The influence of CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Tregs) on cancer
      progression has been demonstrated in a large number of preclinical models and
      confirmed in several types of malignancies. Neoplastic processes trigger an
      increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors,
      leading to the suppression of anti-tumor responses. Treg-depletion before or
      early in tumor development may lead to complete tumor eradication and extends
      survival of mice and humans. However this strategy is ineffective in established
      tumors, highlighting the critical role of the early Treg-tumor encounters. In
      this review, after discussing old and new concepts of immunological tumor
      tolerance, we focus on the nature (thymus-derived vs. peripherally derived) and
      status (naive or activated/memory) of the regulatory T-cells at tumor emergence.
      The recent discoveries in this field suggest that the activation status of Tregs
      and effector T-cells (Teffs) at the first encounter with the tumor are essential
      to shape the fate and speed of the immune response across a variety of tumor
      models. The relative timing of activation/recruitment of anti-tumor cells vs.
      tolerogenic cells at tumor emergence appears to be crucial in the identification
      of tumor cells as friend or foe, which has broad implications for the design of
      cancer immunotherapies. 

PMID- 24133491
TI  - Selective up-regulation of arginase-1 in coronary arteries of diabetic patients.
AB  - Coronary artery disease (CAD) remains the leading cause of death in the Western
      societies. Diabetes mellitus (DM) is one of the highly prevalent diseases, which
      remarkably accelerates the development of CAD. Experimental evidence indicates
      that decreased bioavailability of coronary endothelial nitric oxide (NO)
      contributes to the development of CAD in DM. There are recent studies showing
      that a selective impairment of NO synthesis occurs in coronary arteries of DM
      patients, which is mainly due to the limited availability of endothelial NO
      synthase (eNOS) precursor, l-arginine. Importantly, these studies demonstrated
      that DM, independent of the presence of CAD, leads to selective up-regulation of
      arginase-1. Arginase-1 seems to play an important role in limiting l-arginine
      availability in the close proximity of eNOS in vessels of DM patients. This brief
      review examines recent clinical studies demonstrating the pathological role of
      vascular arginase-1 in human diabetes. Whether arginase-1, which is crucial in
      the synthesis of various fundamental polyamines in the body, will represent a
      potent therapeutic target for prevention of DM-associated CAD is still debated. 

PMID- 24133488
TI  - Proteinaceous determinants of surface colonization in bacteria: bacterial
      adhesion and biofilm formation from a protein secretion perspective.
AB  - Bacterial colonization of biotic or abiotic surfaces results from two quite
      distinct physiological processes, namely bacterial adhesion and biofilm
      formation. Broadly speaking, a biofilm is defined as the sessile development of
      microbial cells. Biofilm formation arises following bacterial adhesion but not
      all single bacterial cells adhering reversibly or irreversibly engage inexorably
      into a sessile mode of growth. Among molecular determinants promoting bacterial
      colonization, surface proteins are the most functionally diverse active
      components. To be present on the bacterial cell surface, though, a protein must
      be secreted in the first place. Considering the close association of secreted
      proteins with their cognate secretion systems, the secretome (which refers both
      to the secretion systems and their protein substrates) is a key concept to
      apprehend the protein secretion and related physiological functions. The protein
      secretion systems are here considered in light of the differences in the cell
      envelope architecture between diderm-LPS (archetypal Gram-negative), monoderm
      (archetypal Gram-positive) and diderm-mycolate (archetypal acid-fast) bacteria.
      Besides, their cognate secreted proteins engaged in the bacterial colonization
      process are regarded from single protein to supramolecular protein structure as
      well as the non-classical protein secretion. This state-of-the-art on the
      complement of the secretome (the secretion systems and their cognate effectors)
      involved in the surface colonization process in diderm-LPS and monoderm bacteria
      paves the way for future research directions in the field. 

PMID- 24133493
TI  - The Influence of Mucus Microstructure and Rheology in Helicobacter pylori
      Infection.
AB  - The bacterium Helicobacter pylori (H. pylori), has evolved to survive in the
      highly acidic environment of the stomach and colonize on the epithelial surface
      of the gastric mucosa. Its pathogenic effects are well known to cause gastritis,
      peptic ulcers, and gastric cancer. In order to infect the stomach and establish
      colonies on the mucus epithelial surface, the bacterium has to move across the
      gel-like gastric mucus lining of the stomach under acidic conditions. In this
      review we address the question of how the bacterium gets past the protective
      mucus barrier from a biophysical perspective. We begin by reviewing the molecular
      structure of gastric mucin and discuss the current state of understanding
      concerning mucin polymerization and low pH induced gelation. We then focus on the
      viscoelasticity of mucin in view of its relevance to the transport of particles
      and bacteria across mucus, the key first step in H. pylori infection. The second
      part of the review focuses on the motility of H. pylori in mucin solutions and
      gels, and how infection with H. pylori in turn impacts the viscoelastic
      properties of mucin. We present recent microscopic results tracking the motion of
      H. pylori in mucin solutions and gels. We then discuss how the biochemical
      strategy of urea hydrolysis required for survival in the acid is also relevant to
      the mechanism that enables flagella-driven swimming across the mucus gel layer.
      Other aspects of the influence of H. pylori infection such as, altering gastric
      mucin expression, its rate of production and its composition, and the influence
      of mucin on factors controlling H. pylori virulence and proliferation are briefly
      discussed with references to relevant literature. 

PMID- 24133492
TI  - Immune activation and collateral damage in AIDS pathogenesis.
AB  - In the past decade, evidence has accumulated that human immunodeficiency virus
      (HIV)-induced chronic immune activation drives progression to AIDS. Studies among
      different monkey species have shown that the difference between pathological and
      non-pathological infection is determined by the response of the immune system to
      the virus, rather than its cytopathicity. Here we review the current
      understanding of the various mechanisms driving chronic immune activation in HIV
      infection, the cell types involved, its effects on HIV-specific immunity, and how
      persistent inflammation may cause AIDS and the wide spectrum of non-AIDS related
      pathology. We argue that therapeutic relief of inflammation may be beneficial to
      delay HIV-disease progression and to reduce non-AIDS related pathological side
      effects of HIV-induced chronic immune stimulation. 

PMID- 24133494
TI  - MHC Class II Polymorphisms, Autoreactive T-Cells, and Autoimmunity.
AB  - Major histocompatibility complex (MHC) genes, also known as human leukocyte
      antigen genes (HLA) in humans, are the prevailing contributors of genetic
      susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D), multiple
      sclerosis, and rheumatoid arthritis, among others (1-3). Although the pathways
      through which MHC molecules afford autoimmune risk or resistance remain to be
      fully mapped out, it is generally accepted that they do so by shaping the central
      and peripheral T-cell repertoires of the host toward autoimmune proclivity or
      resistance, respectively. Disease-predisposing MHC alleles would both spare
      autoreactive thymocytes from central tolerance and bias their development toward
      a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote
      central deletion of autoreactive thymocytes and skew their development toward non
      pathogenic phenotypes. This interpretation of the data is at odds with two other
      observations: that in MHC-heterozygous individuals, resistance is dominant over
      susceptibility; and that it is difficult to understand how deletion of one or a
      few clonal autoreactive T-cell types would suffice to curb autoimmune responses
      driven by hundreds if not thousands of autoreactive T-cell specificities. This
      review provides an update on current advances in our understanding of the
      mechanisms underlying MHC class II-associated autoimmune disease susceptibility
      and/or resistance and attempts to reconcile these seemingly opposing concepts. 

PMID- 24133495
TI  - Modulation of T Cell Metabolism and Function through Calcium Signaling.
AB  - As a vital second messenger in the activation of lymphocytes, the divalent cation
      Ca(2+) plays numerous roles in adaptive immune responses. Importantly, Ca(2+)
      signaling is essential for T cell activation, tolerance of self-antigens, and
      homeostasis. Supporting the essential role of Ca(2+) signaling in T cell biology,
      the Ca(2+) regulated protein phosphatase calcineurin is a key target of
      pharmacologic inhibition for preventing allograft rejection and for autoimmune
      therapy. Recent studies have highlighted the unique role of Stim1 and Orai1/2
      proteins in the regulation of store-operated/calcium release activated calcium
      (CRAC) channels in the context of T cells. While Ca(2+) is known to modulate T
      cell activation via effects on calcineurin and its target, nuclear factor of
      activated T cells (NFAT), this second messenger also regulates other pathways,
      including protein kinase C, calmodulin kinases, and cytoskeletal proteins. Ca(2+)
      also modulates the unique metabolic changes that occur during in distinct T cell
      stages and subsets. Herein, we discuss the means by which Ca(2+) mobilization
      modulates cellular metabolism following T cell receptor ligation. Further, we
      highlight the crosstalk between mitochondrial metabolism, reactive oxygen species
      (ROS) generation, and CRAC channel activity. As a target of mitochondrial ROS and
      Ca(2+) regulation, we describe the involvement of the serine/threonine kinase
      DRAK2 in the context of these processes. Given the important roles for Ca(2+)
      dependent signaling and cellular metabolism in adaptive immune responses, the
      crosstalk between these pathways is likely to be important for the regulation of
      T cell activation, tolerance, and homeostasis. 

PMID- 24133497
TI  - Alloreactivity of virus-specific T cells: possible implication of graft-versus
      host disease and graft-versus-leukemia effects.
AB  - Immune reconstitution of functional virus-specific T cells after allogeneic
      hematopoietic stem cell transplantation (HSCT) has been intensively investigated.
      However, the possible role of crossreactivity of these virus-specific T cells
      against allogeneic targets is still unclear. Theoretically, as in the field of
      organ transplantation, virus-specific T cells possess crossreactivity potential
      after allogeneic HSCT. Such crossreactivity is assumed to play a role in graft
      versus-host disease and graft-versus-leukemia effects. In this article, we aim to
      give a comprehensive overview of current understanding about crossreactivity of
      virus-specific T cells. 

PMID- 24133498
TI  - Thiol-based redox signaling in the nitrogen-fixing symbiosis.
AB  - In nitrogen poor soils legumes establish a symbiotic interaction with rhizobia
      that results in the formation of root nodules. These are unique plant organs
      where bacteria differentiate into bacteroids, which express the nitrogenase
      enzyme complex that reduces atmospheric N 2 to ammonia. Nodule metabolism
      requires a tight control of the concentrations of reactive oxygen and nitrogen
      species (RONS) so that they can perform useful signaling roles while avoiding
      nitro-oxidative damage. In nodules a thiol-dependent regulatory network that
      senses, transmits and responds to redox changes is starting to be elucidated. A
      combination of enzymatic, immunological, pharmacological and molecular analyses
      has allowed us to conclude that glutathione and its legume-specific homolog,
      homoglutathione, are abundant in meristematic and infected cells, that their
      spatio-temporally distribution is correlated with the corresponding
      (homo)glutathione synthetase activities, and that they are crucial for nodule
      development and function. Glutathione is at high concentrations in the bacteroids
      and at moderate amounts in the mitochondria, cytosol and nuclei. Less information
      is available on other components of the network. The expression of multiple
      isoforms of glutathione peroxidases, peroxiredoxins, thioredoxins, glutaredoxins
      and NADPH-thioredoxin reductases has been detected in nodule cells using
      antibodies and proteomics. Peroxiredoxins and thioredoxins are essential to
      regulate and in some cases to detoxify RONS in nodules. Further research is
      necessary to clarify the regulation of the expression and activity of thiol redox
      active proteins in response to abiotic, biotic and developmental cues, their
      interactions with downstream targets by disulfide-exchange reactions, and their
      participation in signaling cascades. The availability of mutants and transgenic
      lines will be crucial to facilitate systematic investigations into the function
      of the various proteins in the legume-rhizobial symbiosis. 

PMID- 24133499
TI  - Modeling branching in cereals.
AB  - Cereals and grasses adapt their structural development to environmental
      conditions and the resources available. The primary adaptive response is a
      variable degree of branching, called tillering in cereals. Especially for
      heterogeneous plant configurations the degree of tillering varies per plant.
      Functional-structural plant modeling (FSPM) is a modeling approach allowing
      simulation of the architectural development of individual plants, culminating in
      the emergent behavior at the canopy level. This paper introduces the principles
      of modeling tillering in FSPM, using (I) a probability approach, forcing the
      dynamics of tillering to correspond to measured probabilities. Such models are
      particularly suitable to evaluate the effect structural variables on system
      performance. (II) Dose-response curves, representing a measured or assumed
      response of tillering to an environmental cue. (III) Mechanistic approaches to
      tillering including control by carbohydrates, hormones, and nutrients. Tiller
      senescence is equally important for the structural development of cereals as
      tiller appearance. Little study has been made of tiller senescence, though
      similar concepts seem to apply as for tiller appearance. 

PMID- 24133500
TI  - Sense-antisense gene pairs: sequence, transcription, and structure are not
      conserved between human and mouse.
AB  - Previous efforts to characterize conservation between the human and mouse genomes
      focused largely on sequence comparisons. These studies are inherently limited
      because they don't account for gene structure differences, which may exist
      despite genomic sequence conservation. Recent high-throughput transcriptome
      studies have revealed widespread and extensive overlaps between genes, and
      transcripts, encoded on both strands of the genomic sequence. This overlapping
      gene organization, which produces sense-antisense (SAS) gene pairs, is capable of
      effecting regulatory cascades through established mechanisms. We present an
      evolutionary conservation assessment of SAS pairs, on three levels: genomic,
      transcriptomic, and structural. From a genome-wide dataset of human SAS pairs, we
      first identified orthologous loci in the mouse genome, then assessed their
      transcription in the mouse, and finally compared the genomic structures of SAS
      pairs expressed in both species. We found that approximately half of human SAS
      loci have single orthologous locations in the mouse genome; however, only half of
      those orthologous locations have SAS transcriptional activity in the mouse. This
      suggests that high human-mouse gene conservation overlooks widespread
      distinctions in SAS pair incidence and expression. We compared gene structures at
      orthologous SAS loci, finding frequent differences in gene structure between
      human and orthologous mouse SAS pair members. Our categorization of human SAS
      pairs with respect to mouse conservation of expression as well as structure
      points to limitations of mouse models. Gene structure differences, including at
      SAS loci, may account for some of the phenotypic distinctions between primates
      and rodents. Genes in non-conserved SAS pairs may contribute to evolutionary
      lineage-specific regulatory outcomes. 

PMID- 24133503
TI  - The mircrine mechanism controlling cardiac stem cell fate.
AB  - The recent identification of c-kit-positive cardiac stem cells revealed the great
      growth reserve of the heart, in which connection among cells might be essential
      in regulating their fate. Especially, the mircrine mechanism, translocation of
      microRNAs (miRs) from a cell to another via gap junctions, appeared to be
      important in controlling the differentiation of cardiac stem cells. The
      modification on miR expression and/or translocation may be able to enhance
      further the clinical efficacy of cellular therapy. 

PMID- 24133502
TI  - Regulation of hepatitis B virus replication by epigenetic mechanisms and
      microRNAs.
AB  - The hepatitis B virus (HBV) genome forms a covalently closed circular DNA
      (cccDNA) minichromosome that persists in the nucleus of virus-infected
      hepatocytes. HBV cccDNA serves as the template for viral mRNA synthesis and is
      subject to epigenetic regulation by several mechanisms, including DNA methylation
      and histone acetylation. Recently, microRNAs (miRNAs), a class of small non
      coding RNAs, were also directly connected to the epigenetic machinery through a
      regulatory loop. Epigenetic modifications have been shown to affect miRNA
      expression, and a sub-group of miRNAs (defined as epi-miRNAs) can directly target
      effectors of the epigenetic machinery. In this review, we will summarize recent
      findings on the epigenetic mechanisms controlling HBV cccDNA function, primarily
      focusing on the epi-miRNA functions operating in HBV replication. Investigation
      of the epigenetic regulation of HBV replication may help to discover novel
      potential therapeutic targets for drug development with the goal to eradicate the
      HBV cccDNA pool in hepatocytes. 

PMID- 24133501
TI  - Human placental trophoblast invasion and differentiation: a particular focus on
      Wnt signaling.
AB  - Wingless ligands, a family of secreted proteins, are critically involved in organ
      development and tissue homeostasis by ensuring balanced rates of stem cell
      proliferation, cell death and differentiation. Wnt signaling components also play
      crucial roles in murine placental development controlling trophoblast lineage
      determination, chorioallantoic fusion and placental branching morphogenesis.
      However, the role of the pathway in human placentation, trophoblast development
      and differentiation is only partly understood. Here, we summarize our present
      knowledge about Wnt signaling in the human placenta and discuss its potential
      role in physiological and aberrant trophoblast invasion, gestational diseases and
      choriocarcinoma formation. Differentiation of proliferative first trimester
      cytotrophoblasts into invasive extravillous trophoblasts is associated with
      nuclear recruitment of beta -catenin and induction of Wnt-dependent T-cell factor
      4 suggesting that canonical Wnt signaling could be important for the formation
      and function of extravillous trophoblasts. Indeed, activation of the pathway was
      shown to promote trophoblast invasion in different in vitro trophoblast model
      systems as well as trophoblast cell fusion. Methylation-mediated silencing of
      inhibitors of Wnt signaling provided evidence for epigenetic activation of the
      pathway in placental tissues and choriocarcinoma cells. Similarly, abundant
      nuclear expression of beta -catenin in invasive trophoblasts of complete
      hydatidiform moles suggested a role for hyper-activated Wnt signaling. In
      contrast, upregulation of Wnt inhibitors was noticed in placentae of women with
      preeclampsia, a disease characterized by shallow trophoblast invasion and
      incomplete spiral artery remodeling. Moreover, changes in Wnt signaling have been
      observed upon cytomegalovirus infection and in recurrent abortions. In summary,
      the current literature suggests a critical role of Wnt signaling in physiological
      and abnormal trophoblast function. 

PMID- 24133496
TI  - Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer
      Vaccine.
AB  - Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human
      population, causing chronic inflammation, which however is largely asymptomatic.
      Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic
      ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer.
      Chronic exposure to the pathogen and its ability to induce epithelial to
      mesenchymal transition (EMT) through the injection of cytotoxin-associated gene A
      into gastric epithelial cells may be key triggers of carcinogenesis. By
      deregulating cell-cell and cell-matrix interactions as well as DNA methylation,
      histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT
      can actively contribute to early stages of the cancer formation. Host response to
      the infection significantly contributes to disease development and the
      concomitance of particular genotypes of both pathogen and host may turn into the
      most severe outcomes. T regulatory cells (Treg) have been recently demonstrated
      to play an important role in H. pylori-related disease development and at the
      same time the Treg-induced tolerance has been proposed as a possible mechanism
      that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori
      infection has significantly dropped. Unfortunately, no vaccine against H. pylori
      is currently licensed, and protective immunity mechanisms against H. pylori are
      only partially understood. In spite of promising results obtained in animal
      models of infection with a number of vaccine candidates, few clinical trials have
      been conducted so far and with no satisfactory outcomes. However, prophylactic
      vaccination may be the only means to efficiently prevent H. pylori-associated
      cancers. 

PMID- 24133504
TI  - The importance and application of the ancestral recombination graph.

PMID- 24133505
TI  - Rotational atherectomy: an Update.

PMID- 24133506
TI  - Application of rotational atherectomy in the drug-eluting stent era.
AB  - Rotational atherectomy (RA) was introduced in the interventional arena in 1988 as
      a dedicated device for calcified lesions. Due to the complexity of the technique,
      the development of alternative methods such as the cutting balloon procedure, and
      the high restenosis rate of subsequent bare metal stenting in long lesions, its
      use had later declined. However, with the increasing use of drug-eluting stents
      (DES) and the aggressive treatment of longer lesions, the number of procedure
      performed with RA has increased significantly again in recent years. In this
      article, we reviewed the application of RA in DES era. 

PMID- 24133507
TI  - Rotablation in the treatment of high-risk patients with heavily calcified left
      main coronary lesions.
AB  - OBJECTIVE: Heavily calcified left-main coronary diseases (LMCA) remain a
      formidable challenge for percutaneous interventions (PCI). This study was to
      investigate the safety and efficacy of using rotational atherectomy (RA) in
      treating such lesions in actual practice. METHODS: From February 2004 to March
      2012, all consecutive patients who received RA for heavily-calcified LMCA lesions
      in our cath lab were enrolled. The relevant clinical and angiographic
      characteristics at the time of index PCI, as well as the clinical follow-up
      outcomes, were retrieved and analyzed. RESULTS: A total of 34 consecutive
      patients were recruited with a mean age 77.2 +/- 10.2 years. There were 82.4%
      presented with acute coronary syndrome and 11.8% with cardiogenic shock. Chronic
      renal disease and diabetes were seen in 64.7% and 52.9%, respectively. Triple
      vessel coronary disease was found in 76.5% of them. The mean SYNTAX score was 50
      +/- 15 and EuroSCORE II scale 5.6 +/- 4.8. The angiographic success rate was 100%
      with a procedural success rate of 91.2%. The mean number of burrs per patient was
      1.7 +/- 0.5. Crossing-over stenting was used in 64.7%. Most stents were drug
      eluting (67.6%). Intra-aortic ballon pump was used in 20.6% of the procedures.
      Three patients died during hospitalization, all due to presenting cardiogenic
      shock. No major complication occurred. Among 31 hospital survivors, the major
      adverse cardiac events (MACE) rate was 16.1%, all due to target lesion
      revascularization or target vessel revascularization. CONCLUSIONS: In high
      surgical-risk elderly patients, plaque modification with RA in PCI of heavily
      calcified LMCA could be safely accomplished with a minimal complication rate and
      low out-of-hospital MACE.

PMID- 24133508
TI  - IVUS-guided rotational atherectomy for unexpandable paclitaxel-eluting stent: A
      case report and review of literature.
AB  - We describe a patient suffering from late stent thrombosis in a paclitaxel
      eluting stent which had an underexpanded ring due to the three-hundred-sixty
      degree circumferential calcified plaque. Intravascular ultrasound (IVUS) revealed
      rotational atherectomy could successfully ablate both the metallic ring and the
      calcified ring. The ablated segment was scaffolded with a new paclitaxel-eluting
      stent, well expanded and documented by IVUS. To our knowledge, this is the first
      case report of stent ablation for an unexpanded paclitaxel-eluting stent. From
      the Medline index, there were only six case reports of stent ablation. We review
      and summarize the operation details of stent ablation from these reports. 

PMID- 24133509
TI  - Mechanism and management of burr entrapment: A nightmare of interventional
      cardiologists.
AB  - Entrapment of the burr within calcified lesion is an uncommon, but serious
      complication during rotational atherectomy and usually needs surgical retrieval.
      We report a case series of this complication and also review the possible
      mechanisms, such as kokesi phenomenon or insufficient pecking motion with
      decreased rotational speed. We also review the potential techniques ever proposed
      to rescue this complication percutaneously, including simple manual traction,
      balloon dilation to release the trap, snaring the burr as distal as possible for
      forceful local traction and wedging the burr with a child catheter to facilitate
      retrieval. Gentle pecking motion of the burr for sufficient ablation and
      shortening the run less than 15 s may avoid such complications. Interventional
      cardiologists using the rotablator should be familiar with the tips and tricks to
      avoid and rescue this complication. 

PMID- 24133510
TI  - One-year clinical outcomes in invasive treatment strategies for acute ST
      elevation myocardial infarction complicated by cardiogenic shock in elderly
      patients.
AB  - OBJECTIVE: To investigate the clinical outcomes of an invasive strategy for
      elderly (aged >= 75 years) patients with acute ST-segment elevation myocardial
      infarction (STEMI) complicated by cardiogenic shock (CS). METHODS: Data on 366 of
      409 elderly CS patients from a total of 6,132 acute STEMI cases enrolled in the
      Korea Acute Myocardial Infarction Registry between January 2008 and June 2011,
      were collected and analyzed. In-hospital deaths and the 1-month and 1-year
      survival rates free from major adverse cardiac events (MACE; defined as all cause
      death, myocardial infarction, and target vessel revascularization) were reported
      for the patients who had undergone invasive (n = 310) and conservative (n = 56)
      treatment strategies. RESULTS: The baseline clinical characteristics were not
      significantly different between the two groups. There were fewer in-hospital
      deaths in the invasive treatment strategy group (23.5% vs. 46.4%, P < 0.001). In
      addition, the 1-year MACE-free survival rate after invasive treatment was
      significantly lower compared with the conservative treatment (51% vs. 66%, P =
      0.001). CONCLUSIONS: In elderly patients with acute STEMI complicated by CS, the
      outcomes of invasive strategy are similar to those in younger patients at the 1
      year follow-up.

PMID- 24133511
TI  - Prevalence of extracardiac findings in the evaluation of ischemic heart disease
      by multidetector computed tomography.
AB  - OBJECTIVE: Multidector computed tomography (MDCT) is now commonly used for the
      evaluation of coronary artery disease. Because MDCT images include many non
      cardiac organs and the patient population evaluated is highly susceptible to
      extracardiac diseases, this study was designed to evaluate the prevalence of
      extracardiac findings in the MDCT evaluation of ischemic heart disease. METHODS:
      From March 2007 to March 2008, a total of six-hundred twenty patients, who
      underwent 64-slice MDCT evaluations for chest pain, or dyspnea, were enrolled in
      this study. Cardiac and non-cardiac findings were comprehensively evaluated by a
      radiologist. RESULTS: Enrolled patients included 306 men (49.4%), with a mean age
      of 66 years. Significant coronary artery stenosis was found in 41.6% of the
      patients. A total of 158 extracardiac findings were observed in 110 (17.7%)
      patients. Commonly involved extracardiac organs were lung (36.7%), hepatobiliary
      system (21.5%), thyroid (19.6%), kidney (10.8%), spine (9.7%) and breast (0.6%).
      Of those 110 patients, 50 (45.5%) patients underwent further diagnostic
      investigations. Malignant disease was detected in three (2.7%) patients (lung
      cancer, pancreatic cancer, and thyroid cancer). CONCLUSIONS: Extracardiac
      findings are frequently present and should be a concern in the MDCT evaluation of
      chest pain syndrome.

PMID- 24133512
TI  - Utility of 64-MSCT in assessing acute non-reperfused myocardial infarct size.
AB  - OBJECTIVE: To evaluate the utility of multi-slice computed tomography (MSCT) in
      assessing acute non-reperfused myocardial infarct size. METHODS: Seven domestic
      pigs (mean weight 17.3 +/- 1.9 kg) underwent ligation of the distal left anterior
      descending artery to establish a model of acute myocardial infarction (MI). MSCT
      and triphenyltetrazolium chloride (TTC) staining were performed two hours later.
      The following data were acquired and analyzed: MI volume (%), CT values of the
      infarcted region, left ventricular cavity and normal cardiac tissue at various
      scanning time-points (1, 5, 10, 15, 20 min after contrast injection). RESULTS:
      Using MSCT, the overall MI volume showed a time-dependent decrease, with a
      reduction of 28.87% after 20 min. The greatest reduction occurred at the 5 min
      time-point. In TTC staining, MI volume was 9.87% +/- 2.44%. When MI size, as
      determined by MSCT, was compared with that by TTC staining in Bland-Altman plots,
      there was a better agreement at 5, 10, and 15 min time-points at 1 and 20 min.
      CONCLUSIONS: The study indicates that double-phase scanning examination using
      MSCT is a useful tool to assess MI size, and the optimal late-phase scanning time
      point set within 5-15 min of contrast injection.

PMID- 24133513
TI  - OptiVol fluid index predicts acute decompensation of heart failure with a high
      rate of unexplained events.
AB  - BACKGROUND: Intrathoracic impedance monitoring has emerged as a promising new
      technique for the detection of impending heart failure (HF). Although false
      positive episodes have been reported in case reports and clinical trials, the
      efficacy and false positive rate in real-world practice remain unclear.
      OBJECTIVE: The aim of this study is to investigate the utility and reliability of
      the OptiVol alert feature in clinical practice. METHODS: We continuously
      recruited patients who underwent implantable cardioverter-defibrillator (ICD) or
      cardiac resynchronization therapy with defibrillator (CRT-D) implantation with
      feature of intrathoracic impedance monitoring system in our center from Sep. 2010
      to Oct. 2012. Regular in-office follow-up were required of all patients and the
      following information was collected at each visit: medical history, device
      interrogation, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement
      and an echocardiogram. Worsening HF was defined as hospitalization or the
      presentation of signs or symptoms of HF. RESULTS: FORTY THREE PATIENTS (MALE:
      76.7%, mean age: 57 +/- 15 years, left ventricular ejection fraction (LVEF): 33%
      +/- 14%) were included in this observational study. Fifty four alert events and
      14 adjudicated worsening HF were detected within 288 +/-163 days follow-up.
      Eleven (20.4%) alert episodes were associated with acute cardiac decompensation
      in 9 patients with a positive predictive value of 78.6%. Forty three audible
      alerts showed no connection to worsening HF. The unexplained alerts rate was
      79.6% and 1.27 per person-year. Thirty seven alarm alerts were detected in
      patients with EF < 45%, among which 9 accompanied with HF, 17 alerts detected in
      patients with LVEF >= 45% and 2 associated with HF. There was no significant
      difference between the two groups (9/37 vs. 2/17; P = 0.47). CONCLUSIONS:
      Patients with normal or nearly normal left ventricular systolic function also
      exhibited considerable alert events. The OptiVol fluid index predicted worsening
      cardiac events with a high unexplained detection rate, and any alert must
      therefore be analyzed with great caution. Efforts to improve the specificity of
      this monitoring system represent a significant aspect of future studies.

PMID- 24133514
TI  - CHADS2 versus CHA2DS2-VASc score in assessing the stroke and thromboembolism risk
      stratification in patients with atrial fibrillation: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of the predictive
      abilities of CHADS2 and CHA2DS2-VASc in stroke and thromboembolism risk
      stratification of atrial fibrillation (AF) patients. METHODS: We searched PubMed
      and EMBASE for English-language literature on comparisons of the diagnostic
      performance between CHADS2 and CHA2DS2-VASc in predicting stroke, or systemic
      embolism, in AF. We then assessed the quality of the included studies and pooled
      the C-statistics and 95% confidence intervals (95% CI). RESULTS: Eight studies
      were included. It was unsuitable to perform a direct meta-analysis because of
      high heterogeneity. When analyzed as a continuous variable, the C-statistic
      ranged from 0.60 to 0.80 (median 0.683) for CHADS2 and 0.64-0.79 (median 0.673)
      for CHA2DS2-VASc. When analyzed as a continuous variable in anticoagulation
      patients, the subgroup analysis showed that the pooled C-statistic (95% CI) was
      0.660 (0.655-0.665) for CHADS2 and 0.667 (0.651-0.683) for CHA2DS2-VASc (no
      significant difference). For non-anticoagulation patients, the pooled C-statistic
      (95% CI) was 0.685 (0.666-0.705) for CHADS2 and 0.675 (0.656-0.694) for CHA2DS2
      VASc (no significant difference). The average ratio of endpoint events in the low
      risk group of CHA2DS2-VASc was less than CHADS2 (0.41% vs. 0.94%, P < 0.05). The
      average proportion of the moderate-risk group of CHA2DS2-VASc was lower than
      CHADS2 (11.12% vs. 30.75%, P < 0.05). CONCLUSIONS: The C-statistic suggests a
      similar clinical utility of the CHADS2 and CHA2DS2-VASc scores in predicting
      stroke and thromboembolism, but CHA2DS2- VASc has the important advantage of
      identifying extremely low-risk patients with atrial fibrillation, as well as
      classifying a lower proportion of patients as moderate risk.

PMID- 24133515
TI  - Impact of diabetes mellitus on pneumonia mortality in a senior population:
      results from the NHANES III follow-up study.
AB  - OBJECTIVE: To examine whether diabetes mellitus increases the risk of pneumonia
      mortality among seniors in the U.S. general population. METHODS & RESULTS: The
      NHANES III follow-up study data were used. After excluding individuals from other
      minorities, being hospitalized with pneumonia in the previous year at baseline,
      or death of pneumonia during the first year of follow-up, a total of 3,707
      subjects aged 65 years or older (1,794 men and 1,913 women) who had no missing
      information on variables for the analysis were included. Approximately 16% of
      seniors at baseline were diabetics, which was defined as either having been
      diagnosed by a physician, currently taking pills/insulin lowering blood glucose,
      or HbA1c higher than 6.4%. During an average 11 years of follow-up, a total of 98
      deaths due to pneumonia were recorded (ICD-10: J12-J18). Cox-regression models
      were used to estimate the risk association between pneumonia mortality and
      diabetes mellitus. After adjustment for the covariates at baseline, the hazard
      ratios of pneumonia death were 1.30 (95% CI: 0.64-2.70) for pre-diabetics and
      2.28 (95% CI: 1.18-4.39) for diabetics, respectively. Among those covariates,
      only age (HR (95% CI); 1.16 (1.13-1.20)), gender as female (0.35 (0.22-0.61)) and
      physical fitness measured as having no problem walking 1(+) mile during the
      previous month (0.38 (0.20-0.67)) reached statistical significance. CONCLUSIONS:
      The results suggest that diabetes mellitus is a strong risk predictor of
      pneumonia mortality and the evaluation of physical fitness may also be useful in
      the risk prediction of pneumonia mortality for seniors.

PMID- 24133516
TI  - Purification and functional assessment of smooth muscle cells derived from mouse
      embryonic stem cells.
AB  - OBJECTIVE: To obtain a pure population of smooth muscle cells (SMC) derived from
      mouse embryonic stem cells (ESC) and further assess their functions. METHODS: A
      vector, expressing both puromycin resistance gene (puro(r) ) and enhanced green
      fluorescent protein (EGFP) gene driven by smooth muscle 22alpha (SM22alpha)
      promoter, named pSM22alpha-puro(r)-IRES2-EGFP was constructed and used to
      transfect ESC. Transgenic ESC (Tg-ESC) clones were selected by G418 and
      identified by PCR amplification of puro(r) gene. The characteristics of Tg-ESC
      were detected by alkaline phosphatase (ALP) staining, SSEA-1 immunofluorescence
      and teratoma formation test in vivo. After induction of SMC differentiation by
      all-trans retinoic acid, differentiated Tg-ESC were treated with 10 ug/mL
      puromycin for three days to obtain purified SMC (P-SMC). Percentage of EGFP(+)
      cells in P-SMC was assessed by flow cytometer. Expressions of smooth muscle
      specific markers were detected by immunostaining and Western blotting.
      Proliferation, migration and contractility of P-SMC were analyzed by growth
      curve, trans-well migration assay, and carbachol treatment, respectively.
      Finally, both P-SMC and unpurified SMC (unP-SMC) were injected into syngeneic
      mouse to see teratoma development. RESULTS: Tg-ESC clone was successfully
      established and confirmed by PCR detection of puro(r) gene in its genomic DNA.
      The Tg-ESC was positive for ALP staining, SSEA-1 staining and formed teratoma
      containing tissues derived from three germ layers. After retinoic acid induction,
      large amount of EGFP positive cells outgrew from differentiated Tg-ESC. Three
      days of puromycin treatment produced a population of P-SMC with an EGFP(+)
      percentage as high as 98.2% in contrast to 29.47% of unP-SMC. Compared with
      primary mouse vascular smooth muscle cells (VSMC), P-SMC displayed positive, but
      lowered expression of SMC-specific markers including SM alpha-actin and myosin
      heavy chain (SM-MHC) detected either, by immunostaining, or immunoblotting,
      accelerated proliferation, improved migration (99.33 +/- 2.04 vs. 44.00 +/- 2.08
      migrated cells/field, P < 0.05), and decreased contractility in response to
      carbachol (7.75 +/- 1.19 % vs. 16.50 +/- 3.76 % in cell area reduction, P <
      0.05). In vivo injection of unP-SMC developed apparent teratoma while P-SMC did
      not. CONCLUSIONS: We obtained a pure population of ESC derived SMC with less
      mature (differentiated) phenotypes, which will be of great use in research of
      vascular diseases and in bio-engineered vascular grafts for regenerative
      medicine.

PMID- 24133517
TI  - GRK 2 level in peripheral blood lymphocytes of elderly patients with acute
      myocardial infarction.
AB  - OBJECTIVE: To investigate the G protein-coupled receptor kinase 2 (GRK 2) level
      in peripheral blood lymphocytes with cardiac function in elderly patients with
      acute myocardial infarction. METHODS: This study enrolled 40 patients with acute
      ST-segment elevation myocardial infarction (STEMI) and 40 patients with unstable
      angina. All patients were 65 years or older. Cardiac function was evaluated by
      echocardiography, and the GRK 2 level in peripheral blood lymphocytes was
      measured. Patients with STEMI were followed up for 2 years. RESULTS: The GRK 2
      level in peripheral blood lymphocytes was significantly higher in patients with
      STEMI than in patients with unstable angina, and was negatively correlated with
      left ventricular ejection fraction, cardiac output, stroke volume, and left
      ventricular fractional shortening. The GRK 2 level was significantly elevated in
      some patients with acute STEMI and poor cardiac function. CONCLUSIONS: Increased
      GRK 2 level in patients with acute STEMI may contribute to poor myocardial
      systolic function and myocardial remodeling. Measurement of the GRK 2 level in
      peripheral blood lymphocytes may assist in the evaluation of cardiac function and
      myocardial remodeling in elderly patients with acute STEMI.

PMID- 24133518
TI  - Serum cystatin C concentration as an independent marker for hypertensive left
      ventricular hypertrophy.
AB  - BACKGROUND: Serum cystatin C levels can be used to predict morbidity and
      mortality in patients with cardiovascular disease. However, the clinical
      relevance of serum cystatin C levels in patients with hypertensive left
      ventricular hypertrophy (LVH) has rarely been investigated. We designed the
      present study to investigate whether serum cystatin C levels are associated with
      cardiac structural and functional alterations in hypertensive patients. METHODS:
      We enrolled 823 hypertensive patients and classified them into two groups: those
      with LVH (n = 287) and those without LVH (n = 536). All patients underwent
      echocardiography and serum cystatin C testing. We analyzed the relationship
      between serum cystatin C levels and LVH. RESULTS: Serum cystatin C levels were
      higher in hypertensive patients with LVH than in those without LVH (P < 0.05).
      Using linear correlation analysis, we found a positive correlation between serum
      cystatin C levels and interventricular septal thickness (r = 0.247, P < 0.01),
      posterior wall thickness (r = 0.216, P < 0.01), and left ventricular weight index
      (r = 0.347, P < 0.01). When analyzed by multiple linear regression, the positive
      correlations remained between serum cystatin C and interventricular septal
      thickness (beta = 0.167, P < 0.05), posterior wall thickness (beta = 0.187, P <
      0.05), and left ventricular weight index (beta = 0.245, P < 0.01). CONCLUSION:
      Serum cystatin C concentration is an independent marker for hypertensive LVH.

PMID- 24133520
TI  - A successful team treatment for left main shock syndrome.
AB  - Acute myocardial infarction complicated by cardiogenic shock and left main
      coronary artery disease is called left main shock syndrome. It is reported that
      the morbility and mortality of the syndrome is approximately 0.46% and 55%-80%,
      respectively. However, the best treatment strategy in these cases is unknown. In
      this article, we present a patient with LMSS who successively underwent emergency
      percutaneous coronary intervention and coronary artery bypass grafting with
      hemodynamic support within 5 days. The patient is now on his three month
      uneventful out-patient follow-up. 

PMID- 24133521
TI  - From the Editor-in-Chief.

PMID- 24133519
TI  - Blood rheology and aging.
AB  - The flow properties of blood play significant roles in tissue perfusion by
      contributing to hydrodynamic resistance in blood vessels. These properties are
      influenced by pathophysiological processes, thereby increasing the clinical
      relevance of blood rheology information. There is well-established clinical
      evidence for impaired blood fluidity in humans of advanced age, including
      enhanced plasma and whole blood viscosity, impaired red blood cell (RBC)
      deformability and enhanced RBC aggregation. Increased plasma fibrinogen
      concentration is a common finding in many studies owing to the pro-inflammatory
      condition of aged individuals; this finding of increased fibrinogen concentration
      explains the higher plasma viscosity and RBC aggregation in elderly subjects.
      Enhanced oxidant stress in advanced age is also known to contribute to altered
      blood fluidity, with RBC deformability being an important determinant of blood
      viscosity. Several studies have shown that physical activity may improve the
      hemorheological picture in elderly subjects, yet well-designed observational and
      mechanistic studies are required to determine the specific effects of regular
      exercise on hemorheological parameters in healthy and older individuals. 

PMID- 24133522
TI  - To prevent the osteoporosis playing in advance.
AB  - There are several possibilities for the prevention of primary, secondary and
      tertiary osteoporosis but till now they have not been promoted enough and bone
      fragility is thought about only after the onset of a fracture (tertiary
      prevention). By recent studies and discoveries it is becoming increasingly clear
      that there is a relationship between growth and development in early childhood
      and bone health in old age. Suboptimal bone development leads to a reduction in
      peak bone mass, and a higher risk of osteoporotic fracture later in life.
      Preventative strategies against osteoporosis can be aimed at either optimizing
      the peak bone mass obtained, or reducing the rate of bone loss. Optimization of
      peak bone mass may be more amenable to public health strategies. Technological
      advances and our knowledge of osteoporosis have increased in the last decade and
      so tertiary prevention should be considered a failure in the field of public
      health. If we want to make advances in the osteoporotic field, we must start in
      childhood, before the bone mass peak is reached and the gold-standard is starting
      with prevention as soon as possible, also during fetal development. 

PMID- 24133523
TI  - Inside the "fragile" infant: pathophysiology, molecular background, risk factors
      and investigation of neonatal osteopenia.
AB  - Current research in bone mineral metabolism reveals many aspects of osteopenia
      occurred in premature infants. This review examines not only the
      pathophysiological and molecular mechanisms of newborn osteopenia but also the
      risk factors and investigation. Osteopenia of premature infants has increased
      incidence among other diseases of prematurity. Identification of risk factors is
      essential for monitoring of osteopenia. Some of the risk factors include low
      birth weight, prematurity, long term administration of drugs such as
      corticosteroids, methyloxanthines, furosemide, abnormalities in vitamin D
      metabolism, poor maternal nutritional and mineral uptake etc. Neonatologists,
      pediatricians and endocrinologists should investigate premature, low birth weight
      infants that have high serum alkaline phosphatase and have at least one risk
      factor. 

PMID- 24133524
TI  - Fall prevention in the elderly.
AB  - Falls are frequent in the elderly and affect mortality, morbidity, loss of
      functional capacity and institutionalization. In the older patient the incidence
      of falls can sometimes be underestimated, even in the absence of a clear
      cognitive impairment, because it is often difficult to reconstruct the dynamics.
      It is quite common that forms due to syncope are associated with retrograde
      amnesia and in 40 to 60% of the cases falls happen in the absence of witnesses.
      The pathogenesis of falls is often multifactorial, due to physiological age
      related changes or more properly pathological factors, or due to the environment.
      The identification of risk factors is essential in the planning of preventive
      measures. Syncope is one of major causes of falls. About 20% of cardiovascular
      syncope in patients older than 70 appears as a fall and more than 20% of older
      people with Carotid Sinus Syndrome complain of falls as well as syncope. These
      data clearly state that older patients with history of falls should undergo a
      cardiovascular and neuroautonomic assessment besides the survey of other risk
      factors. Multifactorial assessment requires a synergy of various specialists. The
      geriatrician coordinates the multidisciplinary intervention in order to make the
      most effective evaluation of the risk of falling, searching for all predisposing
      factors, aiming towards a program of prevention. In clear pathological conditions
      it is possible to enact a specific treatment. Particular attention must indeed be
      paid to the re-evaluation of drug therapy, with dose adjustments or withdrawal
      especially for antihypertensive, diuretics and benzodiazepines. The Guidelines of
      the American Geriatrics Society recommend modification of environmental hazards,
      training paths, hip protectors and appropriate use of support tools (sticks,
      walkers), which can be effective elements of a multifactorial intervention
      program. Balance exercises are also recommended. In conclusion, an initial
      assessment, supported by a comprehensive cardiovascular and neuroautonomic
      evaluation, allows for reaching a final diagnosis in most cases, demonstrating a
      key role in the real identification of the etiology of the fall and implementing
      the treatment measures. 

PMID- 24133525
TI  - Biomechanical analysis and rehabilitation in athletes.
AB  - Posture is defined as the position of the body at a given point in time.
      Incorrect relationship among different parts of body produces an higher tension
      on retaining structure that causes postural problems. Posturology is fundamental
      to recognize the relationship between postural attitude and some pathological
      conditions otherwise difficult to recognize. We can use force platform,
      baropodometric or dynamometric platform to analyze tonic postural system and to
      evaluate sensitive receptors. The main injuries in athletes are caused by
      cumulative trauma. Rehabilitation process is divided in three phases: an acute
      phase, a post-acute phase and a "return to play" phase. The goal of prevention
      and rehabilitation is to find and remove stress and pathologic agent, to reduce
      the limitation of the range of motion, control pain and come back to sport. 

PMID- 24133527
TI  - Porous metal for orthopedics implants.
AB  - Porous metal has been introduced to obtain biological fixation and improve
      longevity of orthopedic implants. The new generation of porous metal has
      intriguing characteristics that allows bone healing and high osteointegration of
      the metallic implants. This article gives an overview about biomaterials
      properties of the contemporary class of highly porous metals and about the
      clinical use in orthopaedic surgery. 

PMID- 24133528
TI  - Current medical treatment strategies concerning fracture healing.
AB  - The morbidity and socioeconomic costs associated with bone healing are
      considerable. A number of fractures are complicated by impaired healing. This is
      prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal
      women, and in people with malnutrition. The biologic process of fracture healing
      is complex and impacted by multiple factors. Some of them, such as the
      nutritional and health conditions, are patient-dependent, while others depend on
      the trauma experienced and stability of the fracture. Fracture healing disorders
      negatively affect the patient's quality of life and result in high health-care
      costs, as a second surgery is required to stabilize the fracture and stimulate
      bone biology. Future biotechnologies that accelerate fracture healing may be
      useful tools, which might also prevent the onset of these disorders. We list the
      characteristics of the drugs used for osteoporosis, but we point out in
      particular the use of strontium ranelate and teriparatide in our clinical
      practice in elderly patients, especially females, who reported fractures with
      risk of nonunion. This medical treatment could impaired fracture healing however,
      most of the evidence is obtained in animal studies and very few studies have been
      done in humans. Thus one could hypothesize the possibility of a medical treatment
      both as a preventive and as support to the synthesis. However, no clinical
      studies are available so far, and such studies are warranted before any
      conclusions can be drawn. A positive effect of osteoporosis treatments on bone
      healing is an interesting possibility and merits further clinical research. 

PMID- 24133526
TI  - Painful prosthesis: approaching the patient with persistent pain following total
      hip and knee arthroplasty.
AB  - BACKGROUND: Symptomatic severe osteoarthritis and hip osteoporotic fractures are
      the main conditions requiring total hip arthroplasty (THA), whereas total knee
      arthroplasty (TKA) is mainly performed for pain, disability or deformity due to
      osteoarthritis. After surgery, some patients suffer from "painful prosthesis",
      which currently represents a clinical problem. METHODS: A systematic review of
      scientific literature has been performed. A panel of experts has examined the
      issue of persistent pain following total hip or knee arthroplasty, in order to
      characterize etiopathological mechanisms and define how to cope with this
      condition. RESULTS: Four major categories (non infective, septic, other and
      idiopathic causes) have been identified as possible origin of persistent pain
      after total joint arthroplasty (TJA). Time to surgery, pain level and function
      impairment before surgical intervention, mechanical stress following prosthesis
      implant, osseointegration deficiency, and post-traumatic or allergic inflammatory
      response are all factors playing an important role in causing persistent pain
      after joint arthroplasty. Diagnosis of persistent pain should be made in case of
      post-operative pain (self-reported as VAS >=3) persisting for at least 4 months
      after surgery, or new onset of pain (VAS >=3) after the first 4 months, lasting
      >=2 months. Acute pain reported as VAS score >=7 in patients who underwent TJA
      should be always immediately investigated. CONCLUSIONS: The cause of pain needs
      always to be indentified and removed whenever possible. Implant revision is
      indicated only when septic or aseptic loosening is diagnosed. Current evidence
      has shown that peri-and/or post-operative administration of bisphosphonates may
      have a role in pain management and periprosthetic bone loss prevention.

PMID- 24133529
TI  - Bone and cancer: the osteoncology.
AB  - In recent years clinicians have witnessed a radical change in the relationship
      between bone and cancer, with in particular an increase in bone metastases
      incidence due to an improvement of patients survival. Bone metastases are
      responsible for the high morbidity in cancer patients with a strong clinical
      impact. For all these reasons, efforts have been directed to this important field
      with the foundation of the osteoncology, a new scientific and clinical branch
      involved in the management of patients with bone cancer disease, including
      primary bone tumors and bone metastases. Another innovative and important
      osteoncology topic is the Cancer Treatment Induced Bone Loss (CTIBL) that is
      mainly caused by antitumoral treatment with bone resorption induction. The
      diagnostic and therapeutic options are described briefly in order to highlight
      the importance of the multidisciplinary approach in this new field. 

PMID- 24133530
TI  - The second hip fracture in osteoporotic patients: not only an orthopaedic matter.
AB  - The second hip fracture indicates the fracture of the osteoporotic femoral neck
      which occurs in patients already operated on the opposite side. It is a growing
      problem, especially in Italy where the ageing rate of the population is one of
      the highest in the world. Only in recent years this issue has been discussed in
      the international literature about timing and the treatment methods as a
      consequence linked to the social costs, mortality, disability of this pathology.
      The aim of our study is the evaluation of the incidence of hip fractures in a
      sample of patients that already substained a surgical procedure for a proximal
      femour fracture. The evaluation was based on the time elapsed between the two
      fractures, the quality of life after the second fractural episode through a
      telephone questionnaire (EQ-5D), the incidence of mortality, the adhesion to the
      antifractural therapy and the comparison of the obtained data to the
      international standards. 

PMID- 24133531
TI  - Disuse osteoporosis of the upper limb: assessment of thirty patients.
AB  - Osteoporosis is a multifactorial skeletal disorder characterized by the decrease
      of bone mass and the alteration of bone microarchitecture that leads to the
      increase of fracture risks. Traditionally, osteoporosis has been classified into
      primary and secondary osteoporosis. Primary osteoporosis refers to osteoporotic
      conditions which are not related to other chronic illnesses and is usually
      associated with aging and decreased gonadal function, such as decreased level of
      estrogen, whereas secondary osteoporosis is the type of osteoporosis caused by
      other health problems. Disuse is one of the many reasons inducing bone loss and
      resulting in secondary osteoporosis. The disuse osteoporosis appeared for the
      first time in the literature in 1974 when Minaire reported some histomorphometric
      analysis of iliac crest bone biopsies performed after a spinal cord injury. The
      most common skeleton sites in which disuse osteoporosis can be observed are knees
      and ankles. THERE ARE THREE CLINICAL SITUATION IN WHICH THIS DISEASE CAN BE
      OBSERVED: neurological or muscular disease that causes a pathological and
      prolonged immobilization. The most frequent is caused by a spinal cord injury,
      long term bed rest or space flight that causes the immobilization linked to
      changes in mechanical environment and experimental immobilizations in healthy
      subjects. Physical exercise is essential for increasing or maintaining bone mass
      and strength. In our study we wondered if the disuse of the upper limbs of a
      certain entity, lasting for a long time, can cause a decrease in BMD quantifiable
      with a densitometric evaluation of the distal radius and with an evaluation of
      the humeral cortical index such as to define a real osteoporosis from disuse. We
      analyzed 30 female patients without secondary osteoporosis older than 60 years:
      everyone underwent to vit D evaluation, densitometric exams of spine, hip and
      distal radius, Constant score and femoral and humeral cortical index evaluation.
      We observed that the distal radius BMD and humeral cortical index were worse in
      patients with low upper limb functionality than in patients with normal shoulder
      function. The results of this study suggest that humeral cortical index and
      radial BMD can be useful methods of upper limb bone density evaluation and that
      they can be useful to select a correct surgical treatment in orthopaedic and
      traumatologic diseases. 

PMID- 24133532
TI  - COL1A1 Sp1 variation and bone phenotypes in an Italian population.
AB  - BACKGROUND: Osteoporosis is the most common metabolic bone disorder of the
      elderly, affecting the normal bone turnover with an increased bone resorption and
      subsequent higher risk of fragility fractures. Collagen type 1 is the most
      represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of
      COL1A1 gene has been associated to modulation of expression of the alpha 1 chain
      of collagen type 1 and it is considered a candidate polymorphism for
      predisposition to osteoporosis status and fragility fractures. Association
      studies, in ethnically different populations, are needed to strongly confirm the
      role of this polymorphism in bone metabolism. MATERIALS AND METHODS: We enrolled
      over 2,000 Italian individuals and studied their bone mineral density (BMD) and
      fractures in relation to age, sex and body mass index (BMI). Moreover, we
      analyzed the distribution of Sp1 polymorphism in these individuals and associated
      it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and
      the presence of low-trauma fractures. RESULTS: The most rare ss genotype showed a
      trend for osteoporosis diagnosis with respect to both normal and osteopenic
      status. The same genotype resulted to be associated to lower values of BMD both
      at spine and femur sites. No association was found with fractures. DISCUSSION: In
      conclusion the presence of the homozygote ss genotype seemed to predispose to
      osteoporosis diagnosis and to be more frequent in subjects with lower spine and
      femur BMD values.

PMID- 24133534
TI  - A physician remembered thanks to the work of the Renaissance Florentine
      sculptors.

PMID- 24133533
TI  - Osteonecrosis of the jaw in a patient with rheumatoid artritis treated with an
      oral aminobisphosphonate: a clinical case report.
AB  - Osteonecrosis of the jaw (ONJ) has been recently described after intravenous
      administration of amino-bisphosphonates and - less frequently - in association
      with the use of oral bisphosphonates. Bisphosphonate-Related Osteonecrosis of the
      Jaw (BRONJ) may affect mandible bone (65%), maxilla bone (26%) and rarely (9%)
      both sites simultaneously. Although causality may never be proven, emerging
      experimental data have established a strong association between monthly
      intravenous bisphosphonate administration and ONJ. Current level of evidence does
      not fully support a cause and effect relationship between the use of oral BPs and
      ONJ. In this paper, we report a clinical case of BRONJ in a 73 years old woman
      affected by rheumatoid arthritis (RA) and periodontitis, after three years of
      treatment with alendronate 70 mg one a week, plus daily calcium and vitamin D.
      The patient developed a tooth abscess at the lower jaw, accompanied by increased
      inflammatory markers, that never returned to normal range despite antibiotic
      therapy, inducing deterioration of joint synovium. The worsening of joint status
      after the onset of ONJ was reflected by the progressive increase in the number of
      swollen (SJ) and tender (TJ) joints, by the deterioration of the score DAS 28
      (which passed from 5.46 to 7.07), pain (with VAS increasing from 60 to 90), and
      by a progressively impaired quality of life, as reported using the HAQ score
      (from 1,25 to 2,5). The patient was switched to antifracture therapy with
      strontium ranelate and the osteonecrosis was successfully treated with
      antibiotics, surgical curettage and local ultrasounds. 

PMID- 24133536
TI  - Relevance of pharmacoepidemiology to Nepal.
AB  - Drug-related problems such as overuse of injectable drug products and
      antimicrobials, increased cost of drug therapy, polypharmacy, and adverse drug
      reactions (ADRs) are prevalent in the healthcare settings of Nepal. To date, no
      new drug development processes or clinical trials have been conducted in Nepal,
      despite the fact that studies of real life situations are an essential tool for
      monitoring medicine use. Pharmacoepidemiology (PE) is an important area that
      evaluates the effects of drug use in large populations. Data obtained from
      pharmacoepidemiological studies may highlight ways to reduce certain drug-related
      problems and provide reliable information on the safety profile of a drug.
      Moreover, clinicians and regulatory authorities may also use the data to make
      drug therapy decisions, drug regulation and policy development. Therefore, there
      is a great need to conduct appropriate pharmacoepidemiological studies that
      involve multiple regions and in various groups of the population of Nepal, to
      collect unbiased and reliable information on drug use. 

PMID- 24133535
TI  - Aetiological agents of ventilator-associated pneumonia and its resistance pattern
      - a threat for treatment.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a common type of nosocomial
      pneumonia encountered in intensive care units. There are several aetiological
      agents which make treatment challenging. Improper antibiotic treatment of
      ventilated patients may lead to the emergence of multidrug resistant (MDR)
      pathogens. METHOD: A prospective study was performed over a period of 20 months.
      Our study had two arms: the first, 'Incidence and risk factors of VAP in a
      tertiary care hospital' was the subject of an earlier publication; we therefore
      present the second investigative arm in this work. The aetiological agents of
      patients on mechanical ventilation (MV) were identified by standard
      bacteriological method. The susceptibility pattern was evaluated by Kirby-Bauer
      disc diffusion method. Extended spectrum beta lactamase (ESBL) testing was
      performed by combination disc method, and metallo-beta lactamase (MBL) testing
      was performed by EDTA disk synergy test (EDS). RESULTS: Late-onset VAP was
      associated with Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia
      coli, while early-onset VAP was commonly caused by members of Enterobacteriaceae,
      Candida albicans and Staphylococcus aureus. 72.2 per cent of VAP patients had
      monomicrobial and 27.8 per cent had polymicrobial infection. Out of the 24
      isolates obtained from patients with VAP, seven (29.2 per cent) were MDR
      pathogens. ESBL and MBL production was detected in 40 per cent and 20 per cent of
      Klebsiella pneumoniae isolated in our study. Around 50 per cent of isolates
      associated with late-onset VAP were MDR, while 22.2 per cent isolates obtained
      from patients with earlyonset VAP were MDR. CONCLUSION: VAP is a nosocomial
      pneumonia that is common among ventilated patients. The aetiological agents vary
      from common organisms to MDR pathogens that are difficult to treat. A proper
      knowledge of MDR pathogens and early isolation followed by prevention of
      prolonged antibiotic therapy can reduce the mortality of late onset VAP.

PMID- 24133537
TI  - Efficacy and perceived utility of podcasts as a supplementary teaching aid among
      first-year dental students.
AB  - BACKGROUND: The advent of newer technology and students' growing familiarity with
      it has enabled information providers to introduce newer teaching methods such as
      audio podcasting in education. Inclusion of audio podcasts as a teaching aid for
      undergraduate medical or dental students could serve as a useful supplement to
      make reviewing more convenient and to enhance understanding and recall of the
      subject matter. AIMS: To assess the efficacy of podcasts as a supplementary
      teaching and learning aid for first-year dental students of Manipal.To study
      students' attitudes towards audio podcasts and perceived utility of podcasts.
      METHOD: This study was conducted at the Manipal College of Dental Sciences,
      India. The participants were first-year dental students. Live lecture classes
      were conducted for the students (n=80). The students were then divided randomly
      into two equal groups of 40 each. Group 1 students (n=40) had a study session
      followed by a multiple choice question (MCQ) test. This was followed by a
      podcasting session. Group 2 students had a study session along with an
      opportunity to listen to a podcast, followed by the test. Following this both
      groups completed a feedback form intended to assess their perceived utility and
      attitude towards podcasts. The performance score was analysed using SPSS and an
      independent sample t test was used to test the significance of differences in the
      mean score between the two groups. RESULTS: Our analysis revealed a significant
      difference (p = 0.000) in the mean score between the two groups. Group 1 scored a
      mean of 7.95 out of 13 and group 2 scored a mean of 6.05 out of 13. Analysis of
      the feedback forms showed that 91.3 per cent of the students found the podcasts
      useful, as they could listen to lecture content repeatedly and at their own
      convenience. Sixty-three per cent of the students, however, felt that the absence
      of images and diagrams in podcasts was a disadvantage. CONCLUSION: Students
      benefited when podcasts were used to supplement live lectures and textbook
      content. This was indicated by better student performance in the podcast group.
      Also, students showed a favourable attitude for podcasts being used as a
      supplementary teaching and learning aid.

PMID- 24133538
TI  - Chromoblastomycosis - A clinical mimic of squamous carcinoma.
AB  - Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous
      tissue caused by dematiaceous fungi. We report a case of chromoblastomycosis
      caused by Fonsecaea pedrosoi from a subtropical region of India that developed
      over the left foot of a 45-year-old male farmer and was provisionally diagnosed
      as squamous cell carcinoma. The patient presented with irregular warty growths
      over the left foot, which had started one year previously, and has gradually
      progressed over a year to involve the lateral aspect of left leg. The diagnosis
      of chromoblastomycosis was confirmed by histopathology and fungal culture. 

PMID- 24133539
TI  - Student attitude towards communication skills learning in a Caribbean medical
      school.
AB  - BACKGROUND: Medical student attitudes towards communication skills are important
      for curriculum planners and teachers. Xavier University School of Medicine
      (XUSOM) is a private medical school admitting students mainly from the United
      States and Canada. AIMS: Attitude of students towards communication skills has
      not been previously studied in the institution. Hence the present study was
      carried out. METHOD: The study was carried out among the first, second, third and
      fourth semester undergraduate medical (MD) students at XUSOM, Aruba during July
      2013 using the communication skills attitude scale (CSAS). Respondents' age,
      gender, nationality, occupation of parents, place of residence of family,
      semester of study were noted. The positive and negative attitude scale scores
      were calculated and compared among different subgroups of respondents (p<0.05).
      RESULTS: Fifty-one of the seventy-three students (69.9 per cent) participated.
      The majority were between 20 to 25 years of age, of American nationality, from
      metro cities and had excellent or good self-perceived verbal and written
      communication skills. The mean positive attitude scale (PAS) score was 47.65
      (maximum being 65) and the mean negative attitude scale (NAS) score was 31.06
      (maximum 65). PAS score was significantly higher among respondents whose fathers
      were not in health related professions. NAS scores were significantly lower among
      the third and fourth semester respondents. CONCLUSION: Students overall had a
      positive attitude towards communication skills but negative attitudes were also
      noted Based on results of the study and a review of literature we are planning to
      start communication skills learning in the institution right from the first
      semester and students will be provided opportunities for supervised practice
      during early clinical exposure, hospital observership and with standardised
      patients. The medical humanities module will be expanded and communication skills
      learning will continue during the clinical years with higher order skills being
      taught.

PMID- 24133540
TI  - Pattern of injury in fatal road traffic accidents in a rural area of western
      Maharashtra, India.
AB  - BACKGROUND: Fatal road traffic accidents (RTA) are a major cause of concern all
      over the world. The outcome of injuries sustained in an RTA depends on various
      factors including but not limited to: the location of the event, type of vehicle
      involved, nature of the roads, the time of accident, etc. AIMS: This study aims
      to investigate and evaluate prospectively the socio-demographic profile and
      pattern of injuries in victims of RTA in the rural area of the Ahmedanagar
      district of Maharashtra state. METHOD: This prospective study included all
      victims of RTA that presented to our emergency room from 1 June 2007 to 31 May
      2009 and were either found dead on arrival or died during treatment. All the
      victims were autopsied at the post-mortem centre of Rural Medical College, Loni.
      RESULTS: Ninety-eight RTA victims were studied during the period. The most
      commonly affected age group was 20-39 years. Men died in RTA more than women.
      Fatal RTA were more prevalent on the secondary road system (47.97 per cent) and
      especially involved pedestrian and two wheeler vehicle users. Large numbers
      (n=63, 64.28%) of victims either died on the scene or during transportation.
      Numbers of skeletal injuries (199) and internal organ injuries (202) exceeded the
      total number of victims (98) clearly indicating the multiplicity of injuries. The
      majority of RTA victims (n=46, 46.93%) died due to head injury. The study showed
      that most deaths in RTA, brought to a tertiary care rural hospital, took place
      either on the spot or within 24 hours of injury which is very alarming and
      highlights the need to take urgent steps to establish good pre-hospital care and
      provision of trauma services at site. CONCLUSION: A computerised trauma registry
      is urgently needed to highlight risk factors, circumstances and chains of events
      leading to accidents. This would be extremely helpful in policy making and health
      management in India.

PMID- 24133541
TI  - Magnesium sulphate versus phenytoin in eclampsia - Maternal and foetal outcome -
      A comparative study.
AB  - BACKGROUND: Eclampsia manifests as seizures and is unique to the pregnant state.
      It remains an important cause of maternal mortality especially in resource
      challenged countries that lack access to prenatal care. AIMS: The aim of our
      study was to compare maternal and foetal outcomes in mothers with eclampsia with
      the administration of either magnesium sulphate or phenytoin in a resource-
      challenged situation. METHOD: The work was conducted from January 2012 to
      December 2012. A total of 80 patients were assigned alternately to two groups -
      one group was treated with magnesium sulphate (Group-M; n=40), and the other
      treated with phenytoin (Group-P; n=40) (Figure 1). The magnesium sulphate was
      administered according to Pritchard's regimen; phenytoin administered according
      to Ryan's regimen. With either regimen, anticonvulsant therapy was continued for
      24 hours postpartum or 24 hours after the last convulsion, whichever was later.
      RESULTS: Fifty-four per cent of patients regained consciousness within eight
      hours of treatment onset in Group-P compared to 5.3 per cent in Group-M
      (p=0.0001, chi(2)=19.24). Seven patients in Group-P had recurrence of convulsions
      as compared to none of the 40 women assigned to Group-M (p=0.032, chi(2)=4.62).
      The incidence of Caesarean section was greater (62.5 per cent) in Group-M
      compared to Group-P (25 per cent; p=0.001, chi(2)= 9.96). No statistically
      significant differences were found in the foetal outcomes between the two groups.
      CONCLUSION: Phenytoin use may be reconsidered in selective cases in low and
      middle income countries (LMIC) as it has been found simpler to use, has several
      benefits and also curtails treatment cost. Magnesium sulphate is substantially
      more effective than phenytoin with regard to recurrence of convulsions. Proper
      training in the management of eclampsia should be given to all health care
      workers to ensure appropriate management of eclamptic mothers. Thus, the
      treatment of this disease calls for more research especially in resource
      challenged settings.

PMID- 24133542
TI  - Nosocomial infections - a present and future challenge.

PMID- 24133543
TI  - Nosocomial infection and antibiotic use: a second national prevalence study in
      Germany.
AB  - BACKGROUND: In 2011, seventeen years after the first national study on the
      prevalence of nosocomial infections and antibiotic use in German hospitals, a
      second national prevalence study was carried out according to the specifications
      of the European Centre for Disease Prevention and Control (ECDC). METHODS: The
      ECDC protocol, containing uniform surveillance definitions and ascertainment
      methods, was implemented. The only infections counted were those that were active
      or under treatment with antibiotics on the day of the study. In addition to the
      representative sample required by the ECDC, which consisted of 46 hospitals,
      further hospitals participated on a voluntary basis. RESULTS: Data on 41 539
      patients in 132 hospitals were analyzed. The prevalence of infections that had
      arisen during the current hospital stay was 3.8% in the overall group and 3.4% in
      the representative sample of 9626 patients in 46 hospitals. The prevalence of all
      nosocomial infections, including those acquired before the current hospital stay
      and still present upon admission, was 5.1% in both the overall group and the
      representative sample. The prevalence of antibiotic use on the day of the study
      was 25.5% and 23.3% in the two groups, respectively. CONCLUSION: The prevalence
      of nosocomial infection has not changed since 1994, but the prevalence of
      antibiotic use has increased. In interpreting these findings, one should bear in
      mind that confounders may have influenced them in different directions: The mean
      length of hospital stay is now shorter than in 1994, but the mean age of
      hospitalized patients is higher.

PMID- 24133546
TI  - Correspondence (letter to the editor): Punctuality is an expression of respect.

PMID- 24133545
TI  - Adult patients with nosocomial pneumonia: epidemiology, diagnosis, and treatment.
AB  - BACKGROUND: Nosocomial pneumonia is among the most common types of infection in
      hospitalized patients. The increasing prevalence of multi-drug resistant
      organisms (MDROs) in recent years points to the need for an up-to-date clinical
      guideline. METHODS: An interdisciplinary S3 guideline was created on the basis of
      a systematic literature review in the PubMed and Cochrane Library databases, with
      assessment and grading of the evidence according to the GRADE system. RESULTS:
      9097 abstracts and 808 articles were screened in full text, and 22
      recommendations were issued. It is recommended that any antimicrobial treatment
      should be preceded by a microbiological diagnostic evaluation with cultures of
      blood and respiratory samples. The diagnosis of nosocomial pneumonia should be
      suspected in any patient with a new or worsened pulmonary infiltrate who meets
      any two of the following three criteria: leucocyte count above 10,000 or below
      4000/uL, temperature above 38.3 degrees C, and/or the presence of purulent
      respiratory secretions. The initially calculated antimicrobial treatment should
      be begun without delay; it should be oriented to the locally prevailing
      resistance pattern, and its intensity should be a function of the risk of
      infection with MDROs. The initial treatment should be combination therapy if
      there is a high risk of MDRO infection and/or if the patient is in septic shock.
      In the new guideline, emphasis is laid on a strict de-escalation concept. In
      particular, antimicrobial treatment usually should not be continued for longer
      than eight days. CONCLUSION: The new guideline's recommendations are intended to
      encourage rational use of antibiotics, so that antimicrobial treatment will be
      highly effective while the unnecessary selection of multi-drug-resistant
      organisms will be avoided.

PMID- 24133547
TI  - Correspondence (letter to the editor): Target times are inconsistent.

PMID- 24133548
TI  - Correspondence (letter to the editor): different specialties need to be
      considered.

PMID- 24133549
TI  - Correspondence (reply): In reply.

PMID- 24133550
TI  - Biophysical mechanisms of the neutralization of endotoxins by lipopolyamines.
AB  - Endotoxins (lipopolysaccharides, LPS) are one of the strongest immunostimulators
      in nature, responsible for beneficial effects at low, and pathophysiological
      effects at high concentrations, the latter frequently leading to sepsis and
      septic shock associated with high mortality in critical care settings. There are
      no drugs specifically targeting the pathophysiology of sepsis, and new
      therapeutic agents are therefore urgently needed. The lipopolyamines are a novel
      class of small molecules designed to sequester and neutralize LPS. To understand
      the mechanisms underlying the binding and neutralization of LPS toxicity, we have
      performed detailed biophysical analyses of the interactions of LPS with candidate
      lipopolyamines which differ in their potencies of LPS neutralization. We examined
      gel-to-liquid crystalline phase behavior of LPS and of its supramolecular
      aggregate structures in the absence and presence of lipopolyamines, the ability
      of such compounds to incorporate into different membrane systems, and the
      thermodynamics of the LPS:lipopolyamine binding. We have found that the
      mechanisms which govern the inactivation process of LPS obey similar rules as
      found for other active endotoxin neutralizers such as certain antimicrobial
      peptides. 

PMID- 24133551
TI  - Successful Treatment with Agomelatine in NES: A Series of Five Cases.
AB  - The NES is an emerging disease in eating behavior that combines eating disorders,
      sleep, mood and stress. In recent years, the NES is becoming more interested in
      close association with obesity and depression. In the present study we have
      followed for 12 weeks 5 patients (2 males and 3 females) with NES and comorbid
      depression treated with agomelatine (25 mg / day for the first two weeks, then 50
      mg / day), an antidepressant similar of melatonin. At the end of the three months
      of treatment, it was found an improvement in symptoms characteristic of the NES,
      as assessed by a reduction an average of the NEQ (from 31 to 22.8), improved
      mood, mean values reduced by 23, 2 to 13.2 on the HAM-D, weight reduction, an
      average of 3.6 kg reduction in average weekly awakenings from 12 to 6.4 and the
      time of snoring and motion detected polysomnography. The serum chemistry values
      remained stable and there were no reported adverse events. The present study
      showed that the treatment with agomelatine has improved the symptoms of NES and
      mood, decrease of body weight, reduce, albeit not in an optimal manner, the
      number of awakenings per night with a reduction of movement time and snoring . Of
      course, these preliminary data need to be confirmed by controlled trials on a
      larger sample. 

PMID- 24133552
TI  - Joint pain undergoes a transition in accordance with signal changes of bones
      detected by MRI in hip osteoarthritis.
AB  - OBJECTIVES: In this study, we aimed to investigate whether joint pain is derived
      from cartilage or bone alterations. METHODS: We reviewed 23 hip joints of 21
      patients with primary hip osteoarthritis (OA), which were classified into
      Kellgren-Laurence (KL) grading I to IV. Plain radiographs and magnetic resonance
      imaging (MRI) were obtained from all of the 23 joints. Two of the 21 patients had
      bilateral hip OA. Pain was assessed based on the pain scale of Denis. A Welch t
      test was performed for age, height, weight, body mass index, bone mineral
      density, and a Mann-Whitney U test was performed for KL grading. RESULTS: Four of
      8 hip joints with pain and OA showed broad signal changes detected by MRI.
      Fourteen hip joints without pain, but with OA did not show broad signal changes
      by MRI. Collectively, MRI analyses showed that broad signal changes in OA cases
      without joint pain or with a slight degree of joint pain were not observed, while
      broad signal changes were observed in OA cases with deteriorated joint pain.
      CONCLUSION: Our findings suggest that hip joint pain might be associated with
      bone signal alterations in the hips of OA patients.

PMID- 24133553
TI  - The relationship between neck pain and physical activity.
AB  - Neck pain is a significant societal burden due to its high prevalence and
      healthcare costs. While physical activity can help to manage other forms of
      chronic musculoskeletal pain, little data exists on the relationship between
      physical activity and neck pain. The purpose of this study was to compare
      physical activity levels between individuals with neck pain and healthy controls,
      and then to relate disability, fear of movement, and pain sensitivity measures to
      physical activity levels in each of the two participant groups. 21 participants
      were recruited for each of the two participant groups (n = 42). Data collection
      included the use of the Neck Disability Index, the Tampa Scale for Kinesiophobia,
      electrocutaneous (Neurometer(r) CPT) and pressure stimulation (JTech algometer)
      for quantitative sensory testing, and 5 days of subjective (Rapid Assessment of
      Physical Activity) and objective (BioTrainer II) measurements of physical
      activity. Analysis of Variance and Pearson's Correlation were used to determine
      if differences and relationships exist between dependent variables both within
      and between groups. The results show that individuals with mild neck pain and
      healthy controls do not differ in subjectively and objectively measured physical
      activity. While participants with neck pain reported higher neck disability and
      fear of movement, these factors did not significantly relate to physical activity
      levels. Perceived activity level was related to pain threshold and tolerance at
      local neck muscles sites (C2 paraspinal muscle and upper trapezius muscle),
      whereas measured activity was related to generalized pain sensitivity, as
      measured at the tibialis anterior muscle site. 

PMID- 24133555
TI  - Acetabular component anteversion in primary and revision total hip arthroplasty:
      an observational study.
AB  - PURPOSE: In a prospective manner to evaluate the range of acetabular component
      anteversion actually achieved by the use of a cup positioner in cementless
      revision and primary THA. METHODS: We operated 71 patients with cementless
      primary THA, and 26 patients with cementless acetabular revision surgery. We
      aimed to obtain cup anteversion of 10 to 30 degrees  with an impactor-positioner.
      In all cases we used elevated liners and a ceramic head with diameter 28. At 3
      months postoperatively the component versions were measured using CT with the
      patient in supine position. RESULTS: The acetabular component version in the
      primary hips ranged from 28 degrees  of retroversion to 42 degrees  of
      anteversion with a mean of 17.4 +/- 14.0 degrees , while the cup version in the
      revision hips ranged from 4 degrees  of retroversion to 32 degrees  of
      anteversion with a mean of 15.0 +/- 9.6 degrees (p=0.427). The anteversion of 40
      (56%) of the primary acetabular components were within the target zone of 10 to
      30 degrees , while 19 (27%) were below the target zone and and 12 (17%) were
      above the target range. The anteversion of 19 (73%) of the revision acetabular
      components were within the target zone, while 6 (23%) were below the target zone
      and 1 (4%) were above the target range. The differences in distribution between
      the primary and revision operations were not significant (p=0.183). CONCLUSIONS:
      The intraoperative estimation of acetabular anteversion by free hand technique in
      many cases was not within the intended range of 10 to 30 degrees  in either
      primary or revision THA and with no differences between the two series.

PMID- 24133554
TI  - Psychological Care, Patient Education, Orthotics, Ergonomics and Prevention
      Strategies for Neck Pain: An Systematic Overview Update as Part of the ICON
      Project.
AB  - OBJECTIVES: To conduct an overview on psychological interventions, orthoses,
      patient education, ergonomics, and 10/20 neck pain prevention for adults with
      acute-chronic neck pain. SEARCH STRATEGY: Computerized databases and grey
      literature were searched (2006-2012). SELECTION CRITERIA: Systematic reviews of
      randomized controlled trials (RCTs) on pain, function/disability, global
      perceived effect, quality-of-life and patient satisfaction were retrieved. DATA
      COLLECTION &AMP ANALYSIS: Two independent authors selected articles, assessed
      risk of bias using AMSTAR tool and extracted data. The GRADE tool was used to
      evaluate the body of evidence and an external panel to provide critical review.
      MAIN RESULTS: We retrieved 30 reviews (5-9 AMSTAR score) reporting on 75 RCTs
      with the following moderate GRADE evidence. For acute whiplash associated
      disorder (WAD), an education video in emergency rooms (1RCT, 405participants]
      favoured pain reduction at long-term follow-up thus helping 1 in 23 people
      [Standard Mean Difference: -0.44(95%CI: -0.66 to -0.23)). Use of a soft collar
      (2RCTs, 1278participants) was not beneficial in the long-term. For chronic neck
      pain, a mind-body intervention (2RCTs, 1 meta-analysis, 191participants) improved
      short-term pain/function in 1 of 4 or 6 participants. In workers, 2-minutes of
      daily scapula-thoracic endurance training (1RCT, 127participants) over 10 weeks
      was beneficial in 1 of 4 participants. A number of psychosocial interventions,
      workplace interventions, collar use and self-management educational strategies
      were not beneficial. REVIEWERS' CONCLUSIONS: Moderate evidence exists for
      quantifying beneficial and non-beneficial effects of a limited number of
      interventions for acute WAD and chronic neck pain. Larger trials with more
      rigorous controls need to target promising interventions.

PMID- 24133556
TI  - Efficacy of intravitreal ranibizumab injection in acute nonarteritic ischemic
      optic neuropathy: a long-term follow up.
AB  - BACKGROUND: To evaluate the effect of a single intravitreal ranibizumab injection
      in eyes with acute nonarteritic ischemic optic neuropathy (NAION). SUBJECTS AND
      METHODS: In this retrospective clinical data analysis, 17 eyes of sixteen
      patients who experienced a visual loss with duration of 15 days or less comprised
      the study group. In addition to standard ophthalmic examination, retinal nerve
      fiber layer thickness (RNFLT) analysis with spectral domain OCT was also
      performed prior to 0.5 mg Ranibizumab injection, one week, one, three, six months
      and one year after the injection. RESULTS: The mean time between visual loss and
      intravitreal injection was 7.5 days (Range, 2-15 days). Mean age of patients was
      59 years (Range, 41-90 years). Male to female ratio was 6:10. After a single dose
      of ranibizumab injection, visual gain was noted in 14 of 17 study eyes. In two
      eyes, visual acuity was minimally reduced and no change was noted in the
      remaining eye with an initial visual acuity of hand motions. While pre-injection
      mean best-corrected visual acuity (BCVA) was 1.45 +/-0.88 log Mar unit, post
      injection mean BCVA was 1.00+/-0.68, 0.86 +/-0.70, 0.80 +/-0.71, 0.77 +/-0.70,
      0.77 +/-0.70 log Mar unit respectively at the first week, first month, third
      month, sixth month and first year. In all patients, the mean RNFLT dramatically
      decreased after the injection during the follow- up. While pre-injection mean
      RNFLT was 210 +/-38 um, post-injection mean RNFLT was 162.11+/-40.2, 94+/-27,
      71.23+/-22.5, 63 +/-19 and 57 +/-18 um respectively at the first week, first
      month, third month, sixth month and first year. No injection related complication
      was noted during the follow-up period. CONCLUSION: Intravitreal ranibizumab
      injection can be a treatment modality in eyes with acute NAION.

PMID- 24133557
TI  - Do Men who have Sex with Men (MSM) in the United States Understand that HIV
      Serodiscordance is Possible?
AB  - BACKGROUND: Little is currently known about the extent to which US MSM understand
      the possibility that a long-term sex partner can have an HIV status different
      than one's own status. This information is important in the adaptation of Couples
      Voluntary HIV Counseling and Testing (CVCT) for US MSM. METHODS: 428 US MSM
      completed an online survey using MySpace.com from March-April, 2009. RESULTS: Of
      426 MSM with complete data, 21.1% (90) were not definitively aware that
      serodiscordance is possible. Factors associated with a lack of understanding that
      serodiscordance is possible were: never having tested for HIV (OR: 2.0; CI: 1.1,
      3.8), compared to testing 0-6 months previously and having a high school
      education or less (OR: 2.2; CI: 1.1, 4.5), compared to men who had completed at
      least some college. CONCLUSIONS: A large proportion of young, internet-using MSM
      in the United States may not understand that HIV serodiscordance is possible
      within sexual partnerships. Based on these results, we recommend that CVCT
      provided to male couples in the United States should include education on HIV
      serodiscordance.

PMID- 24133558
TI  - mHealth for HIV Treatment & Prevention: A Systematic Review of the Literature.
AB  - This systematic review assesses the published literature to describe the
      landscape of mobile health technology (mHealth) for HIV/AIDS and the evidence
      supporting the use of these tools to address the HIV prevention, care, and
      treatment cascade. The speed of innovation, broad range of initiatives and tools,
      and heterogeneity in reporting have made it difficult to uncover and synthesize
      knowledge on how mHealth tools might be effective in addressing the HIV pandemic.
      To do address this gap, a team of reviewers collected literature on the use of
      mobile technology for HIV/AIDS among health, engineering, and social science
      literature databases and analyzed a final set of 62 articles. Articles were
      systematically coded, assessed for scientific rigor, and sorted for HIV
      programmatic relevance. The review revealed evidence that mHealth tools support
      HIV programmatic priorities, including: linkage to care, retention in care, and
      adherence to antiretroviral treatment. In terms of technical features, mHealth
      tools facilitate alerts and reminders, data collection, direct voice
      communication, educational messaging, information on demand, and more. Studies
      were mostly descriptive with a growing number of quasi-experimental and
      experimental designs. There was a lack of evidence around the use of mHealth
      tools to address the needs of key populations, including pregnant mothers, sex
      workers, users of injection drugs, and men who have sex with men. The science and
      practice of mHealth for HIV are evolving rapidly, but still in their early
      stages. Small-scale efforts, pilot projects, and preliminary descriptive studies
      are advancing and there is a promising trend toward implementing mHealth
      innovation that is feasible and acceptable within low-resource settings, positive
      program outcomes, operational improvements, and rigorous study design. 

PMID- 24133559
TI  - Life-threatening pharyngeal edema after sclerotherapy of oral venous
      malformations in a patient with blue rubber bleb nevus syndrome.
AB  - BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder
      characterized by multiple venous malformations of the skin and internal organs.
      Oral lesions are very common and occur in over half of the patients with this
      condition. Sclerotherapy is currently the first-line treatment modality of
      symptomatic cases due to its high efficacy and low rate of complications. MAIN
      OBSERVATIONS: We report the case of a 68-year-old male with BRBNS who presented
      with dysphagia and difficulty with speech due to prominent oral venous
      malformations. After the use of sclerotherapy with ethanolamine oleate to control
      his symptoms, the patient exhibited severe edema of the tongue and posterior
      pharyngeal wall which caused constriction of his airway. The patient was
      intubated, and remained so for 72 hours until his edema resolved. In addition to
      his oral lesions, the patient also exhibited other features of BRBNS including
      cutaneous, soft-tissue, gastrointestinal, and neurological manifestations of
      disease. CONCLUSION: Physicians should be aware of the potentially life
      threatening complication of severe tongue and pharyngeal edema when using
      sclerotherapy for the treatment of oral vascular malformations. Additionally,
      dermatologists should be familiar with the many systemic manifestations which can
      be present in patients with BRBNS, as illustrated in this case.

PMID- 24133560
TI  - Pentoxifylline-induced drug rash with eosinophilia and systemic symptoms (DRESS)
      in a patient with caffeine intolerance.
AB  - BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe
      drug reaction characterised by rash, eosinophilia and systemic involvement. MAIN
      OBSERVATIONS: We report a case of DRESS induced by pentoxifylline used for the
      treatment of severe alcoholic hepatitis, in a patient with longstanding caffeine
      intolerance. A history of intolerance to caffeine and other methylxanthines is
      listed as a contraindication to the use of pentoxifylline, yet this precaution is
      not mentioned in alcoholic hepatitis treatment guidelines. CONCLUSIONS:
      Prescribers should always seek a history of intolerance to caffeine and related
      compounds prior to use of pentoxifylline, as severe life threatening reactions
      can occur.

PMID- 24133561
TI  - Psoriasis treated successfully with ustekinumab in a cocaine-addicted patient.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory disease
      estimated approximately in 2% of the European population. Drug abuse is reported
      in 3-5% of the global population. MAIN OBSERVATION: We present a 41-year-old,
      cocaine-addicted patient male with severe plaque-type psoriasis treated
      successfully with ustekinumab. The patient received ustekinumab at a dose of 45
      mg subcutaneously at weeks 0, 4 and 16 and achieved PASI 75 at week 18.
      CONCLUSIONS: Although several drug-abusers experience psoriasis, literature is
      very poor regarding the outcome of systemic treatment in those patients. In our
      patient no adverse effects were seen during the administration period of
      ustekinumab and no interactions between cocaine and ustekinumab were noticed.
      Nevertheless, more individuals and further studies are needed to establish the
      efficacy and safety of ustekinumab in the treatment of psoriasis in drug-abusers.

PMID- 24133562
TI  - Squamous cell carcinoma in lichen planopilaris.
AB  - BACKGROUND: Lichen planopilaris (LPP) is a rare variant of cutaneous lichen
      planus that preferentially involves hair follicles. OBSERVATION: We describe the
      case of an 87-year-old woman with cicatricial alopecia due to lichen
      planopilaris. The diagnosis was based on clinical evaluation, histopathology and
      trichoscopy. Squamous cell carcinoma developed within the hairless area after 18
      years of evolution. CONCLUSION: It is necessary to consider the association
      between lichen planopilaris and squamous cell carcinoma and to ensure a close
      follow-up of LPP patients, especially when there is a long history of the disease
      or new a lesion develops, which does not correspond clinically or in trichoscopy
      to lichen planopilaris.

PMID- 24133563
TI  - A lesion suspected of melanoma by dermoscopy: we must trust this diagnostic tool.
AB  - BACKGROUND: The incidence of cutaneous melanoma is increasing worldwide and early
      diagnosis is essential since the prognosis is poor in advanced stages of disease.
      Dermoscopy emerged as an additional and important diagnostic procedure for the
      early diagnosis of cutaneous melanoma. MAIN OBSERVATION: We report a case of a 52
      year-old man, who developed a pigmented lesion in the right pretibial region.
      Dermoscopy highly suggestive of melanoma. The initial histopathological
      evaluation suggested a benign lesion. Since dermoscopy was very suspicious, a
      more extensive histopathological study of the excised skin fragment was
      performed. This led to a change of diagnosis to a melanoma with partial
      regression. CONCLUSIONS: The present case shows that occasionally dermoscopy may
      be more informative for diagnosis of melanoma than an initial histopathology
      result.

PMID- 24133564
TI  - Coexistence of aplasia cutis congenita, faun tail nevus and fetus papyraceus.
AB  - BACKGROUND: Aplasia cutis congenita is a disorder of the skin embryonic
      development characterized by a defect of localized or widespread areas of skin at
      birth. The lesions are mostly oval, 1-3 cm in diameter, with localization on the
      parietal part of scalp (60%) and rarely on the face and extremities. MAIN
      OBSERVATIONS: Herein, we reported a case of aplasia cutis congenita termly born
      at 39 weeks of gestation to a 30-year-old mother with bronchial asthma attacks.
      She was referred for 3 punched-out punctate depressed defective lesions in 0.4
      cm's diameter on the vertex covered with necrotic and hemorrhagic crusts. There
      was a hypertrichotic area consisting of tufts of terminal hair on the lumbosacral
      area over a sinus tract. Maternal perinatal drugs included aerosol salbutamol
      sulfate, ipratropium bromide and oral montelukast sodium for bronchial asthma.
      The pregnancy was firstly started as a di-chorionic, di-amniotic twin gestation,
      but deteriorated after the fetal resorption of the co-twin in the 20th
      gestational week resulting in fetus papyraceus. CONCLUSION: In multi-gestational
      pregnancies, the presence of the fetus papyraceus or the death of the co-twins
      should make the neonatologists and dermatologists be aware of the possible
      cutaneous defects like aplasia cutis congenita. We emphasize that the possibility
      of this rare entity should be kept in mind in the presence of fetus papyraceus,
      perinatal drug use, maternal cigarette smoke, or maternal diseases like bronchial
      asthma in multiple gestations.

PMID- 24133565
TI  - A Unique Case of Classic Kaposi's sarcoma restricted to the toes.
AB  - BACKGROUND: Kaposi's sarcoma associated-herpesvirus causes all forms of Kaposi's
      sarcoma, and six major subtypes have been described based on the amino acid
      sequences of the open reading frame K1. MAIN OBSERVATION: A 71-year-old man from
      China, HIV negative, presented with nodules on the dorsal aspect of his toes.
      Biopsy confirmed the diagnosis of Kaposi's sarcoma and virology studies of his
      blood and saliva confirmed the presence of Kaposi's sarcoma associated
      herpesvirus infection. Viral genotyping was consistent with subtype C3.
      Intervention has been deferred as our patient has remained clinically
      asymptomatic and without evident growth of his lesions over a 2-year follow up.
      CONCLUSIONS: We herein report the first known case of Kaposi's sarcoma restricted
      to the toes caused by the viral subtype C3 in an HIV-negative patient from
      Harbin, China.

PMID- 24133566
TI  - Photoletter to the editor: Dermatitis herpetiformis co-localised with vitiligo in
      a patient with autoimmune polyglandular syndrome.
AB  - We report a case of dermatitis herpetiformis co-localised with segmental vitiligo
      in a 37-year-old woman with a background history of autoimmune polyglandular
      syndrome type 2. We propose genetic mosaicism as a possible mechanism. There has
      only been one previous case report in which dermatitis hepetiformis co-localised
      in close proximity but not exclusively within vilitigo in a patient with
      autoimmune thyroiditis. To our knowledge, this is the first case report of
      dermatitis herpetiformis co-localised exclusively to segmental vitiligo in the
      presence of autoimmune polyglandular syndrome. 

PMID- 24133567
TI  - Photoletter to the editor: Squamous cell carcinoma associated with and
      masquerading as molluscum contagiosum.
AB  - Squamous cell carcinoma is a non-melanoma skin cancer with a significant risk of
      mortality if not diagnosed promptly. A high index of suspicion is required, since
      it may mimic many benign conditions. Molluscum contagiosum is an innocuous viral
      infection which can also mimic a wide variety of other conditions. We report a
      case of squamous cell carcinoma on the anterior chest wall resembling a giant
      molluscum contagiosum, where the patient also had molluscum contagiosum at other
      sites. In addition, he developed herpes zoster of the left fifth thoracic
      dermatome. After surgical removal of the cancer, there was prompt subsidence of
      the molluscum contagiosum lesions without any specific treatment. This report
      highlights the importance of early biopsy in the diagnosis of squamous cell
      carcinoma. As the patient had no other conditions or therapy that could account
      for the immunosuppression, we hypothesize that the occurrance of molluscum
      contagiosum and zoster along with the squamous cell carcinoma indicates possible
      immunosuppression due to the carcinoma, though no metastatic spread could be
      detected. 

PMID- 24133568
TI  - Letter to the editor: Temporary renal insufficiency associated with topical
      tacrolimus treatment of multilocal pyoderma gangrenosum.

PMID- 24133569
TI  - Impact of advanced (open) access scheduling on patients with chronic diseases: an
      evidence-based analysis.
AB  - BACKGROUND: The goal of advanced access scheduling is to eliminate wait times for
      physician visits by ensuring access to same-day appointments, regardless of
      urgency or health care need. The intent is to reduce delays in access, leading to
      improvements in clinical care and patient satisfaction, and reductions in the use
      of urgent care. OBJECTIVE: To evaluate whether implementation of an advanced
      access scheduling system reduced other types of health service utilization and/or
      improved clinical measures and patient satisfaction among adults with chronic
      diseases. DATA SOURCES AND REVIEW METHODS: A literature search was performed on
      January 29, 2012, for studies published from 1946 (OVID) or 1980 (EMBASE) to
      January 29, 2012. Systematic reviews, randomized controlled trials, and
      observational studies were eligible if they evaluated advanced access
      implementation in adults with chronic diseases and reported health resource
      utilization, patient outcomes, or patient satisfaction. Results were summarized
      descriptively. RESULTS: One systematic review in a primary care population and 4
      observational studies (5 papers) in chronic disease and/or geriatric populations
      were identified. The systematic review concluded that advanced access did not
      improve clinical outcomes, but there was no evidence of harm. Findings from the
      observational studies in chronic disease populations were consistent with those
      of the systematic review. Advanced access implementation was not consistently
      associated with changes in clinical outcomes, patient satisfaction, or health
      service utilization. LIMITATIONS: All studies were retrospective: 3 studies (4
      papers) included historical controls only, and 1 included contemporaneous
      controls. Findings were inconsistent across studies for a number of outcomes.
      CONCLUSIONS: Based on low to very low quality evidence, advanced access did not
      have a statistically (or clinically) significant impact on health service
      utilization among patients with diabetes and/or coronary artery disease (CAD).
      Very low quality evidence showed a significant reduction in the proportion of
      patients with diabetes and CAD admitted to hospital whose length of stay was
      greater than 3 days. Evidence was inconsistent for changes in clinical outcomes
      for patients with diabetes or CAD. Very low quality evidence showed no increase
      in patient satisfaction with an advanced access scheduling system.

PMID- 24133570
TI  - Screening and management of depression for adults with chronic diseases: an
      evidence-based analysis.
AB  - BACKGROUND: Depression is the leading cause of disability and the fourth leading
      contributor to the global burden of disease. In Canada, the 1-year prevalence of
      major depressive disorder was approximately 6% in Canadians 18 and older. A large
      prospective Canadian study reported an increased risk of developing depression in
      people with chronic diseases compared with those without such diseases.
      OBJECTIVES: To systematically review the literature regarding the effectiveness
      of screening for depression and/or anxiety in adults with chronic diseases in the
      community setting. To conduct a non-systematic, post-hoc analysis to evaluate
      whether a screen-and-treat strategy for depression is associated with an
      improvement in chronic disease outcomes. DATA SOURCES: A literature search was
      performed on January 29, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and
      Other Non-Indexed Citations, OVID EMBASE, OVID PsycINFO, EBSCO Cumulative Index
      to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and
      the Centre for Reviews and Dissemination database, for studies published from
      January 1, 2002 until January 29, 2012. REVIEW METHODS: No citations were
      identified for the first objective. For the second, systematic reviews and
      randomized controlled trials that compared depression management for adults with
      chronic disease with usual care/placebo were included. Where possible, the
      results of randomized controlled trials were pooled using a random-effects model.
      RESULTS: Eight primary randomized controlled trials and 1 systematic review were
      included in the post-hoc analysis (objective 2)-1 in people with diabetes, 2 in
      people with heart failure, and 5 in people with coronary artery disease. Across
      all studies, there was no evidence that managing depression improved chronic
      disease outcomes. The quality of evidence (GRADE) ranged from low to moderate.
      Some of the study results (specifically in coronary artery disease populations)
      were suggestive of benefit, but the differences were not significant.
      LIMITATIONS: The included studies varied in duration of treatment and follow-up,
      as well as in included forms of depression. In most of the trials, the authors
      noted a significant placebo response rate that could be attributed to spontaneous
      resolution of depression or mild disease. In some studies, placebo groups may
      have had access to care as a result of screening, since it would be unethical to
      withhold all care. CONCLUSIONS: There was no evidence to suggest that a screen
      and-treat strategy for depression among adults with chronic diseases resulted in
      improved chronic disease outcomes. PLAIN LANGUAGE SUMMARY: People with chronic
      diseases are more likely to have depression than people without chronic diseases.
      This is a problem because depression may make the chronic disease worse or affect
      how a person manages it. Discovering depression earlier may make it easier for
      people to cope with their condition, leading to better health and quality of
      life. We reviewed studies that looked at screening and treating for depression in
      people with chronic diseases. In people with diabetes, treatment of depression
      did not affect clinical measures of diabetes management. In people with heart
      failure and coronary artery disease, treatment of depression did not improve
      heart failure management or reduce rates of heart attacks or death. At present,
      there is no evidence that screening and treating for depression improves the
      symptoms of chronic diseases or lead to use of fewer health care services.

PMID- 24133572
TI  - Ensemble of gene signatures identifies novel biomarkers in colorectal cancer
      activated through PPARgamma and TNFalpha signaling.
AB  - We describe a novel bioinformatic and translational pathology approach, gene
      Signature Finder Algorithm (gSFA) to identify biomarkers associated with
      Colorectal Cancer (CRC) survival. Here a robust set of CRC markers is selected by
      an ensemble method. By using a dataset of 232 gene expression profiles, gSFA
      discovers 16 highly significant small gene signatures. Analysis of dichotomies
      generated by the signatures results in a set of 133 samples stably classified in
      good prognosis group and 56 samples in poor prognosis group, whereas 43 remain
      unreliably classified. AKAP12, DCBLD2, NT5E and SPON1 are particularly
      represented in the signatures and selected for validation in vivo on two
      independent patients cohorts comprising 140 tumor tissues and 60 matched normal
      tissues. Their expression and regulatory programs are investigated in vitro. We
      show that the coupled expression of NT5E and DCBLD2 robustly stratifies our
      patients in two groups (one of which with 100% survival at five years). We show
      that NT5E is a target of the TNF-alpha signaling in vitro; the tumor suppressor
      PPARgamma acts as a novel NT5E antagonist that positively and concomitantly
      regulates DCBLD2 in a cancer cell context-dependent manner. 

PMID- 24133573
TI  - Emblica officinalis extract induces autophagy and inhibits human ovarian cancer
      cell proliferation, angiogenesis, growth of mouse xenograft tumors.
AB  - Patients with ovarian cancer (OC) may be treated with surgery, chemotherapy
      and/or radiation therapy, although none of these strategies are very effective.
      Several plant-based natural products/dietary supplements, including extracts from
      Emblicaofficinalis (Amla), have demonstrated potent anti-neoplastic properties.
      In this study we determined that Amla extract (AE) has anti-proliferative effects
      on OC cells under both in vitro and in vivo conditions. We also determined the
      anti-proliferative effects one of the components of AE, quercetin, on OC cells
      under in vitro conditions. AE did not induce apoptotic cell death, but did
      significantly increase the expression of the autophagic proteins beclin1 and LC3B
      II under in vitro conditions. Quercetin also increased the expression of the
      autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also
      significantly reduced the expression of several angiogenic genes, including
      hypoxia-inducible factor 1alpha (HIF-1alpha) in OVCAR3 cells. AE acted
      synergistically with cisplatin to reduce cell proliferation and increase
      expression of the autophagic proteins beclin1 and LC3B-II under in vitro
      conditions. AE also had anti-proliferative effects and induced the expression of
      the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors.
      Additionally, AE reduced endothelial cell antigen - CD31 positive blood vessels
      and HIF-1alpha expression in mouse xenograft tumors. Together, these studies
      indicate that AE inhibits OC cell growth both in vitro and in vivo possibly via
      inhibition of angiogenesis and activation of autophagy in OC. Thus AE may prove
      useful as an alternative or adjunct therapeutic approach in helping to fight OC. 

PMID- 24133574
TI  - Ovarian stimulation for in vitro fertilization alters the protein profile
      expression in endometrial secretion.
AB  - Failure of the embryo to implant now constitutes the major limiting step in IVF
      treatment. Successful implantation requires a vital embryo and an effective
      molecular dialogue with a 'receptive' endometrium. However, what precisely
      constitutes a receptive human endometrium remains poorly defined. Several
      observations have indicated that ovarian stimulation for IVF may impair
      endometrial receptivity. The histological approach to monitor endometrial
      maturation requires an invasive biopsy that excludes its use during the luteal
      phase of cycles in which implantation is the end-point objective as in IVF. In
      recent years, several studies have been reported that the removal of endometrial
      secretions immediately prior to embryo transfer provides sufficient material for
      analysis of markers of receptivity without disrupting embryo implantation.
      Therefore, analysis of protein patterns in endometrial secretion fluid may offer
      a relatively non-invasive means of assessing endometrial receptivity during
      fertility treatment cycles. Several studies have shown that protein profile
      expression in endometrial secretions undergo cyclical changes, and demonstrated
      significant differences between the natural cycle and stimulated cycle. These
      findings suggest that endometrial secretion analysis provide a novel means of
      investigating the effect of ovarian stimulation on the intrauterine environment
      at the time of embryo transfer, which may help to develop less disruptive ovarian
      stimulation protocols for IVF in the future. 

PMID- 24133575
TI  - Assessment of different decalcifying protocols on Osteopontin and Osteocalcin
      immunostaining in whole bone specimens of arthritis rat model by confocal
      immunofluorescence.
AB  - Confocal immunofluorescence is a valuable technique for the detection of relevant
      molecules in the pathogenesis of arthritis in rat models; however, it requires
      efficient processing of tissues including bone decalcification. The
      decalcification process must ensure the complete removal of calcium and also a
      proper preservation of cellular structures and, specially, the antigenicity of
      the tissue to allow the immunodetection of the molecules of interest. In the
      present study, we evaluated the effect of four different decalcifying solutions:
      the Morse's solution, 10% EDTA (pH 7.4), 7% HCl/2% EDTA and 5% Nitric acid, as
      well as four different treatments of the tissues (including microwave
      irradiation) in the processes of decalcification for large pieces of adult rat
      bones (hind paw, fore paw, knee and column). We assessed the time of
      decalcification, the easiness of slicing, the morphological preservation and
      finally, the antigenicity of two different bone proteins (Osteopontin (OPN) and
      Osteocalcin (OC)) measured by its immunofluorescence intensity under controlled
      confocal microscopy conditions. Our results showed that the specimen size and the
      presence of skin are critical factors for the rate of decalcification, and no
      significant benefit was found if microwave irradiation is applied to the tissue.
      The comprehensive statistical analysis showed that the optimal solution for the
      detection of OPN and OC by confocal immunofluorescence is the 5% Nitric Acid, and
      followed by 10% EDTA (pH 7.4), Ana Morse solution and 7% HCl/2% EDTA. 

PMID- 24133576
TI  - Role of two single nucleotide polymorphisms in secreted frizzled related protein
      1 and bladder cancer risk.
AB  - In this study, we determined the genotype distribution of two single nucleotide
      polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and
      rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of
      the SNPs were determined using restriction fragment length polymorphism (RFLP)
      analysis and partly verified by sequencing analysis. Overall, DNA from 188
      consecutive and 215 early-onset bladder cancer patients (<=45 years) as well as
      from 332 controls was investigated. Potential microRNA binding sites were
      determined for rs3242, and microRNA expression was analysed in cell lines and
      tumour specimens. We observed a remarkable distribution difference in rs3242
      between bladder cancer patients and healthy controls (p=0.05). Additionally, we
      found a significant difference in genotype distribution (p=0.032), resulting from
      the difference of early-onset patients and the control group (p=0.007). The risk
      allele T showed increased frequency in the early-onset patient group (p=0.002).
      Genotype-dependent differences of microRNA binding capacity were predicted in
      SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines
      and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142
      SNP showed no significant association with bladder cancer risk. This is the first
      study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk
      as well as the influence of rs3242 on genotype-dependent microRNA capacity on
      SFRP1 mRNA. The onset of bladder seems to be associated with the increased
      occurrence of the T-allele in rs3242. 

PMID- 24133577
TI  - Cyclosporin A promotes proliferating cell nuclear antigen expression and
      migration of human cytotrophoblast cells via the mitgen-activated protein kinase
      3/1-mediated nuclear factor-kappaB signaling pathways.
AB  - Our previous studies have demonstrated that cyclosporin A (CsA) promotes the
      proliferation and migration of human trophoblasts via the mitgen-activated
      protein kinase-3/1 (MAPK3/1) pathway. In the present study, we further
      investigated the role of nuclear factor (NF)-kappaB in the CsA-induced
      trophoblast proliferating cell nuclear antigen (PCNA) expression and migration,
      and its relationship to MAPK3/1 signal. Flow cytometry was used to analyze the
      expression of PCNA in trophoblasts. The migration of human primary trophoblasts
      was determined by wound-healing assay and transwell migration assay. Western blot
      analysis was performed to evaluate the activation of NF-kappaB p65 and NF-kappaB
      inhibitory protein I-kappaB in human trophoblasts. We found that treatment with
      CsA promotes PCNA expression and migration of human trophoblast in a dose
      associated manner. Blocking of the MAPK3/1 signal abrogated the enhanced PCNA
      expression and migration in trophoblasts by CsA. In addition, CsA increased the
      phosphorylation of NF-kappaB p65 and the inhibitor I-kappaB in human trophoblasts
      in a time-related manner. Pretreatment with MAPK3/1 inhibitor U0126 abrogated the
      phosphorylation of NF-kappaB p65 and I-kappaB. Accordingly, the CsA-induced
      enhancement of PCNA expression and migration in trophoblasts was also decreased.
      This CsA-induced enhancement in the expression and migration of trophoblasts was
      abolished by pretreatment with pyrrolidine dithiocarbamate, a specific NF-kappaB
      inhibitor. Thus, our results suggest that CsA promotes PCNA expression and
      migration of human trophoblasts via MAPK-mediated NF-kappaB activation. 

PMID- 24133578
TI  - IL-22 in the endometriotic milieu promotes the proliferation of endometrial
      stromal cells via stimulating the secretion of CCL2 and IL-8.
AB  - Interleukin-22 (IL-22) is a member of the IL-10 cytokine family and plays
      critical roles in inflammation, immune surveillance, and tissue homeostasis.
      However, whether IL-22 regulates the growth of endometrial stromal cells (ESCs),
      and participates in the pathogenesis of endometriosis remain unclear. In this
      study, we found that the expression of IL-22 and it receptors (IL-22R1 and IL
      10R2) in eutopic endometrium and ectopic lesion of women with endometriosis was
      higher than that from healthy control. Recombinant human IL-22 (rhIL-22)
      stimulated the proliferation of ESCs in a dosage-dependent manner. On the
      contrary, anti-human IL-22 neutralizing antibody inhibited the proliferation of
      ESCs in vitro. The stimulatory effect of IL-22 on the proliferation of ESCs could
      be reversed by inhibitor of STAT5, ERK1/2 or AKT signal pathway. However,
      blocking STAT3, JNK or P38 signal pathway had no these effects. By Enzyme-linked
      immunosorbent assay (ELISA) and flow cytometry assay, we demonstrated the rhIL-22
      not only stimulate the secretion of CCL2 and IL-8, but also significantly up
      regulate the expression of IL-8 receptor CXCR1 on ESCs. Meanwhile, STAT5, ERK1/2
      and or AKT signal inhibitors could abrogate the increase of CCL2, IL-8 and CXCR1
      levels induced by rhIL-22. However, rhIL-22 had not similar influence on CCL2
      receptor CCR2. Our current results suggested that the higher level of IL-22 and
      it receptors in eutopic endometrium may stimulate the expression of CCL2, IL
      8/CXCR1, and further promote the growth of ESCs possibly through activating
      STAT5, MAPK/ERK1/2 and or AKT signal pathways, which may be involved in the
      occurrence and development of endometriosis. 

PMID- 24133579
TI  - Impact of hyperglycemia and acute pancreatitis on the receptor for advanced
      glycation endproducts.
AB  - Since hyperglycemia aggravates acute pancreatitis and also activates the receptor
      for advanced glycation endproducts (RAGE) in other organs, we explored if RAGE is
      expressed in the pancreas and if its expression is regulated during acute
      pancreatitis and hyperglycemia. Acute pancreatitis was induced by cerulein in
      untreated and streptozotocin treated diabetic mice. Expression of RAGE was
      analyzed by Western blot and immunohistochemistry. To evaluate signal
      transduction the phosphorylation of ERK1/ERK2 was assessed by Western blot and
      the progression of acute pancreatitis was monitored by evaluation of lipase
      activity and the pancreas wet to dry weight ratio. RAGE is mainly expressed by
      acinar as well as interstitial cells in the pancreas. During acute pancreatitis
      infiltrating inflammatory cells also express RAGE. Using two distinct anti-RAGE
      antibodies six RAGE proteins with diverse molecular weight are detected in the
      pancreas, whereas just three distinct RAGE proteins are detected in the lung.
      Hyperglycemia, which aggravates acute pancreatitis, significantly reduces the
      production of two RAGE proteins in the inflamed pancreas. 

PMID- 24133580
TI  - NME1 suppression of endometrial stromal cells promotes angiogenesis in the
      endometriotic milieu via stimulating the secretion of IL-8 and VEGF.
AB  - Nonmetastatic gene 23-H1 (NME1, also known as nm23-H1) is a wide-spectrum tumor
      metastasis suppressor gene that plays an important role in suppressing the
      proliferation, adhesion and invasion of endometrial stromal cells (ESCs). The
      present study is undertaken to explore the mechanism by which NME1 in ESCs from
      endometriosis modulates the angiogenesis and herein participates in the
      pathogenesis of endometriosis. The expression of NME1 in the primary ESCs from
      normal endometrium without endometriosis was higher than that from eutopic
      endometrium and ectopic lesion with endometriosis. Silencing NME1 stimulated the
      secretion of angiogenic factors interleukin-8 (IL-8) and vascular-endothelial
      growth factor (VEGF) of the eutopic ESCs from women with endometriosis, and these
      effects could be abrogated by MAPK/ERK1/2 or AKT inhibitor. In addition, the
      supernatant of NME1-silenced ESCs increased the expression of angiogenesis
      relative molecules CD62E and CD105, and promoted angiogenesis of human umbilical
      vein endothelial cells (HUVECs). Anti-human IL-8 or VEGF neutralizing antibody
      reversed the effect on angiogenesis of HUVECs induced by NME1-silenced ESCs. Our
      current results suggest that the abnormal lower expression of NME1 in ESCs
      secrete more IL-8 and VEGF through activation of MAPK/ERK1/2 and AKT signal
      pathways, up-regulate the level of CD62E and CD105, and finally lead to numerous
      angiogenesis of vascular endothelial cells in the endometriotic milieu, which is
      beneficial to the origin and development of endometriosis. 

PMID- 24133581
TI  - Functional regeneration of irradiated salivary glands with human amniotic
      epithelial cells transplantation.
AB  - This study aimed to investigate the functional restoration of radiation-damaged
      salivary gland with human amniotic epithelial cells (hAECs) transplantation by
      intra-glandular injection. hAECs were isolated from the amnion tissues. After
      primary culture, the phenotype of hAECs of the second passage was identified by
      flow cytometry (FCM) and immunocytochemical staining. Then, hAECs were intra
      glandularly injected into the irradiated glands of mice. At different time points
      after transplantation, the glands were collected for hematoxylin-eosin (HE)
      staining and immunofluorescence staining, and the saliva flow rate was also
      determined. Results showed these cells were positive for CD29, CD73 and CK19 and
      negative for CD44, CD34, CD45 and CD71. The transplanted hAECs in the recipient
      glands could differentiate into acinar-like cells and resulted in morphological
      and functional restoration of salivary gland. 

PMID- 24133582
TI  - Clinicopathological study of gene rearrangement and microRNA expression of
      primary central nervous system diffuse large B-cell lymphomas.
AB  - We studied the clinicopathological and imaging characteristics of primary central
      nervous system diffuse large B-cell lymphomas (PCNS-DLBCL). Imaging, pathologic
      histology, and immunohistochemical staining characteristics were analyzed, and
      the immunoglobulin heavy and light chain gene rearrangement of 25 PCNS-DLBCL
      cases was examined. MicroRNA was extracted from 10 cases each of PCNS-DLBCL,
      extracerebral germinal center DLBCL (GC-DLBCL), and extracerebral non-GC-DLBCL
      (NGC-DLBCL); we conducted chip hybridization and comparatively analyzed the
      difference among the three. PCNS-DLBCLs typically involved no less than two
      cerebral lobes (10/25); the frontal lobe was affected most often (6/25). Target
      shaped structures were observed in all PCNS-DLBCLs due to the proliferation of
      centroblast-like large lymphocytes surrounding the vessels. There was strong and
      diffuse immunostaining for CD20 and CD79a, and negative immunostaining for CD3,
      CD5, CD23, and cyclin D1 for all PCNS-DLBCLs. The percentage of cells with
      nuclear positivity for anti-Ki67 antibody ranged 50-90% (mean, 80%). Three, 19,
      and 22 PCNS-DLBCLs were CD10-, Bcl-6-, and melanoma ubiquitous mutated 1
      positive, respectively. Twenty-four PCNS-DLBCLs were B-cell monoclonal. MicroRNA
      hybridization showed that 788 PCNS-DLBCL microRNAs/segments increased to at least
      twice that of NGC-DLBCLs, and 401 PCNS-DLBCL microRNAs/segments declined to less
      than half of that of NGC-DLBCLs. Six hundred and eleven PCNS-DLBCL
      microRNAs/segments increased to at least twice that of GC-DLBCLs, and 229 PCNS
      DLBCL microRNAs/segments declined to less than half of that in GC-DLBCLs. PCNS
      DLBCL typically affected multiple sites, tended to occur in older men, arose from
      activated B cells, had high B-cell monoclonality; its microRNA expression
      differed from that of NGC-DLBCL and GC-DLBCL. 

PMID- 24133583
TI  - Decreased SARI expression predicts poor prognosis of Chinese patients with non
      small cell lung cancer.
AB  - SARI is associated with the risk for several cancers, and loss of SARI expression
      is frequently found in aggressive and metastatic cancer. Limited evidence shows
      that SARI is a tumor suppressor gene, but the role of SARI in non-small cell lung
      cancer (NSCLC) has not been previously reported. This study was to investigate
      the SARI expression profile in surgically resected lung cancer tissues of Chinese
      patients by immunohistochemistry and evaluate the relationship between SARI
      expression and prognosis of lung cancer patients. Furthermore, SARI gene was
      transfected into lung cancer cells (A549), and the growth curve and cell healing
      of lung cancer cells were determined, aiming to investigate the influence of SARI
      on the growth and migration of lung cancer cells in vitro. Results showed that
      103 of 195 (52.82%) tissues were positive for SARI. When compared with normal
      tissues, SARI expression significantly reduced in 50.26% of NSCLC tissues.
      Patients with negative or reduced SARI expression were more likely to have
      advanced lung cancer and lymph node metastasis. In squamous carcinoma and
      adenocarcinoma patients, the SARI expression had no relation with the survival
      time; However in one-on-one analysis SARI expression in tumor cells and adjacent
      tissues, patients which tumor cells SARI express reduced than adjacent tissues,
      survival time was significantly shorter than those without reduction in SARI
      expression (Log Rank test, p = 0.001). After transfection by SARI gene, the
      proliferation and migration of A549 cells were obviously inhibited (p < 0.001).
      These results demonstrate that decreased SARI expression may predict a poor
      prognosis in NSCLC patients, and SARI may serve as a prognostic biomarker and
      potential therapeutic target for lung cancer. 

PMID- 24133584
TI  - Upregulation of ATF-3 is correlated with prognosis and proliferation of laryngeal
      cancer by regulating Cyclin D1 expression.
AB  - OBJECTIVE: This study aimed to investigate the expression and significance of ATF
      3 in laryngeal squamous cell carcinoma (LSCC). METHODS: Expression of ATF-3 was
      examined using immunohistochemistry methods in samples from 83 cases of LSCC
      carcinoma. MTT assay was used to detect proliferation of Hep-2 cells after ATF-3
      knocked down by siRNA lentivirus. A mouse model was used to investigate the
      inhibitive role of ATF-3 siRNA in LSCC xenografts. Realtime RCR was used to
      detect Cyclin D1 expression after ATF-3 downregulation in Hep-2 cells. RESULTS:
      The expression of ATF-3 was positively detected in all the 83 cases of LSCC
      cancer tissues while Only 4 cases of adjacent non-neoplastic tissues were
      detected with positive ATF-3 expression. The ATF-3 expression was statistically
      related with T stage, neck nodal metastasis, clinical stage and prognosis of
      LSCC. Both cell proliferation in vitro and tumor growth in vivo were suppressed
      after ATF-3 knockdown. Furthermore, the expression of Cyclin D1 was decreased
      after ATF-3 downregulation in Hep-2 cells. CONCLUSION: ATF-3 is involved in the
      progress of LSCC, and may provide clinical information for evaluation of
      prognosis of LSCC. The oncologic role of ATF-3 may be correlated with Cyclin D1
      regulation.

PMID- 24133585
TI  - Small interfering RNA survivin and GRIM-19 co-expression salmonella plasmid
      inhibited the growth of laryngeal cancer cells in vitro and in vivo.
AB  - OBJECTIVE: To investigate the inhibitory effect of plasmid-based survivin
      specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer
      cells. METHODS: The plasmid expressing survivin-specific short hairpin RNA
      (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into
      Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving
      and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT
      assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry
      and AO/EB assay were done to determine the apoptosis of Hep-2 cells. RESULTS: In
      the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was
      markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of
      surviving was more obvious than that in the p-siRNA survivin group (37%)
      (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared
      with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2
      cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly
      inhibited, and the inhibition rate was as high as 79%, which was higher than that
      in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow
      cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19
      group were dramatically increased as compared to the psi-survivin group and p
      GRIM-19 group. CONCLUSION: The p-siRNA survivin/GRIM-19 has marked decrease in
      survivin expression and dramatic increase in GRIM-19 expression. Moreover,
      silencing of survivin and over-expression of GRIM-19 can significantly inhibit
      the growth and induce the apoptosis of Hep-2 in vitro and in vivo.

PMID- 24133586
TI  - Systematic screen with kinases inhibitors reveals kinases play distinct roles in
      growth of osteoprogenitor cells.
AB  - Cancer treatment-related bone loss has become growing problematic, especially in
      breast and prostate cancer treated with hormone/endocrine therapy, chemotherapy
      and radiotherapy. However, bone loss caused by targeted therapy in cancer
      patients is largely unknown yet. In present study, a kinase inhibitors screen was
      applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase
      inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and
      Everolimus) were found to suppress the cell viability with dose- and time
      dependent manner. The most interesting is that many kinase inhibitors (such as
      lapatinib, erlotinib and sunitinib) can promote MC3T3-E1 cell proliferation at
      0.01 MUM. 4 out of 7 inhibitors were selected to perform the functional study and
      found that they lead to cell cycle dysregulation, treatments of PF-04691502 (AKT
      inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1
      arrest of MC3T3-E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880
      (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and G2/M phase
      by upregulation of p53 protein. Our work provides important indications for the
      comprehensive care of cancer patients treated with some targeted drugs. 

PMID- 24133587
TI  - Differential expression and subcellular localization of Prohibitin 1 are related
      to tumorigenesis and progression of non-small cell lung cancer.
AB  - Lung cancer remains the leading cause of cancer-related deaths worldwide and non
      small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer.
      With a variety of biological functions, Prohibitin1 (PHB1) has been proved tumor
      associated. But there are conflicting data regarding the involvement of PHB1 in
      tumorigenesis and few studies regarding the role of PHB1 in lung cancer. The
      studies reported herein used a combination of clinical observations and molecular
      methods to investigate the possible role of PHB1 in NSCLC tissues and cell lines.
      PHB1 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and
      immunohistochemistry analysis. Flow cytometric analysis was used to determine the
      surface expression profiles of PHB1 in lung cell lines. The results showed that
      PHB1 expression were generally increased in lung cancer tissues when compared
      with matched noncancerous tissues and closely related with tumor differentiation
      and lymph node invasion. PHB1 expression levels was also increased in three lung
      cancer cell lines (SK-MES-1, NCI-H157 and NCI-H292) as compared with BEAS-2B
      cells. Moreover, there were various subcellular localization of PHB1 in different
      lung cancer cells and the presence of PHB1 on the surface of lung cancer cells
      was significantly reduced. In conclusion, PHB1 expression is increased in NSCLC
      and the up-regulation of PHB1 is associated with clinically aggressive phenotype.
      The different subcellular localization of PHB1 in NSCLC cells and the loss of the
      membrane-associated PHB1 probably related to the tumorigenesis and progression of
      NSCLC and suggests that PHB1 may play different roles in various types of NSCLC. 

PMID- 24133588
TI  - Expression of Id-1 and VEGF in non-small cell lung cancer.
AB  - Angiogenesis is essential for invasive tumor growth and metastasis. Bevacizumab
      has been widely used for the treatment of non-small cell lung cancer (NSCLC).
      Various studies clearly demonstrate the relevance of Id-1 and VEGF in
      angiogenesis. The aim of this study was to establish the role of Id-1 expression
      in tumor progression and angiogenesis in relation to VEGF in NSCLC. Seventy five
      patients underwent surgery for lung cancers. The expressions of Id-1 and VEGF in
      NSCLC samples were determined by immunohistochemistry. Expression of Id-1 and
      VEGF showed a close correlation in NSCLC (p < 0.001). In addition, Id-1 strong
      expression group showed high incidence of metastasis in multivariate analysis (p
      = 0.028). Id-1 strong expression group had short metastasis-free survival (p =
      0.008) and short recurrence-free survival (p = 0.027). Strong Id-1 expression in
      NSCLC had a poor prognosis in association with VEGF expression. Id-1 may function
      in tumor growth and progression via angiogenesis. Therefore, Id-1 is considered
      to be a candidate for new therapeutic target and a prognostic factor in NSCLC. 

PMID- 24133589
TI  - Clinicopathological significance of PTEN and PI3K/AKT signal transduction pathway
      in non-small cell lung cancer.
AB  - A high frequency of mutations at the PTEN locus has been noticed in carcinoma of
      lung. However, the role of PTEN alternations and its association with outcome
      variables in the genesis of lung carcinoma are not understood fully. The purpose
      of our study was to examine the impact of EGFR, TGF-alpha, P-AKT and PTEN in the
      genesis of non-small cell lung cancer (NSCLC). Total numbers of 66
      histopathologically confirmed cases of NSCLC and 10 cases of benign control
      samples embedded with wax were studied. We assessed EGFR, TGF-alpha and P-AKT by
      the use of specific antibody through immunohistochemistry as directed by the
      manufacturer, and detected PTEN expression by in situ hybridization. There were
      progressive loss of PTEN expression and significant increasing in EGFR, TGF
      alpha, P-AKT expression from benign samples to NSCLC (p<0.05). The overexpression
      of EGFR, TGF-alpha, P-AKT and loss of PTEN expression were correlated to
      differentiation extent of cancer tissue, metastasis of lymph nodes and
      histological classification. Thus, alteration of EGFR, TGF-alpha, P-AKT and PTEN
      are likely important molecular events in pathogenesis and carcinogenesis of
      NSCLC. 

PMID- 24133590
TI  - Cytologic changes of ovarian epithelial cancer induced by neoadjuvant
      chemotherapy.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by cytoreduction has now
      become a part of standard care for patients with advanced ovarian cancer.
      Cytologic changes of the cancer cells induced by NACT, however, sometimes may
      cause confusion in terms of pathologic diagnosis and therefore inappropriate
      management. The objective of this study was to characterize the histologic or
      cytologic features of the ovarian cancers from those patients who received NACT
      in order to improve the diagnostic accuracy and reduce unnecessary clinical
      workup. METHODS: Specimens from 120 patients with advanced ovarian cancer who
      received NACT were studied. All 120 cases had either cytologic samples from
      ascites (n=108) or fine needle aspiration (n=12) and the diagnosis of consistent
      with cancers of ovarian origin was made prior to NACT. There were 70 (58.3%)
      patients received subsequent tumor debulking surgery after NACT. The time frame
      between NACT and debulking surgery ranged from 28 to 65 with an average of 45
      days. Among the 70 cases with cytoreductive surgery, 48 cases containing both pre
      NACT cytology/histology and subsequent debulking specimens were suitable for the
      study. All 48 post-NACT ovarian cancers were reviewed and the characteristic
      pathologic features in gross were summarized. Microscopic evaluation and
      immunohistochemical stainings with antibodies against ER, PR, p53, WT1, PAX8,
      CK7, CK20, and CDX2 were performed to confirm the primary site and histologic
      type of the cancers. RESULTS: Grossly, tumor size within the ovaries from those
      debulking specimens ranged from 2.3 to 6.5 cm in greatest dimension. The cancers
      were mainly solid (average of 65%) and cystic areas had more or less hemorrhagic
      appearance. Extensive tumor necrosis and some with fibrosis were present.
      Microscopically, the non-necrotic cancer cells were arranged in cords, islands
      and sometimes as scattered single large cells with large amount of eosinophilic
      cytoplasm with vacuoles. The viable cancer cells contained more or less
      vacuolated cytoplasm in almost all post chemotherapy cases. Multinucleated tumor
      giant cells were noted in close to half of the cases. The cancer cells commonly
      had large hyperchromatic bizarre nuclei with coarse chromatin clumping and
      sometimes prominent nucleoli. Due to the unusual cytologic changes after NACT,
      there was a concern of non-ovarian origin or the different histologic type of the
      cancers. Therefore, immunohistochemical (IHC) staining with the antibodies
      against ER, PR, PAX8, WT1, CK7, CK20, and CDX2 was performed in all 48 pairs of
      the cases. The 48 paired samples showed identical immunophenotype in pre- and
      post-NACT cancers, confirming there was no metastatic or new primary cancer
      involved in the study. CONCLUSIONS: NACT can apparently induce significant
      cytologic/histologic changes in ovarian cancer. Aware of such NACT induced
      changes will be useful to make correct diagnosis for those patients who have
      received NACT. IHC with appropriate panels of the antibodies will be helpful to
      aid the diagnosis, particularly when nuclear change is dramatic and the clinical
      history of ovarian cancer is not available.

PMID- 24133591
TI  - MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1beta induced
      in human endometriosis stromal cells in vitro.
AB  - OBJECTIVE: Now there are more and more evidences that Cyclooxygenase-2 (COX-2)
      plays an important role in angiogenesis of endometriosis (EMs). Vascular
      endothelial growth factor (VEGF) has a potent angiogenic activity. However, it is
      worth studying about the regulating mechanism of COX-2/COX-1 and VEGF in the
      development of human endometriosis in vitro. The current study was designed to
      investigate the effect of 4 cytokines on COX-2/COX-1 expression and the effect of
      IL-1beta on VEGF release in human endometriosis stromal cells (ESC), and to
      explore the related signaling pathways involved in vitro. METHODS: Isolation,
      culture and identification of ESC. Cells were treated with 4 cytokines, and the
      inhibitor mitogen-activated protein-Erk (MEK) and the inhibitor p38 mitogen
      activated protein kinase (MAPK) prior to adding cytokine IL-1beta. COX-2 protein
      expression was measured by western blot and VEGF secretion was determined by
      ELISA. RESULTS: Among four kinds of cytokines, IL-1beta treatment increased COX-2
      protein expression and VEGF release in three ESC, and TNF-alpha had the same
      effect on COX-2 protein level as IL-1beta only in ectopic and eutopic ESC, and
      MCSF had only slight effect on ectopic ESC. In contrast, cytokines had no effect
      on COX-1 expression. We also demonstrated that MAPK reduced the synthesis of COX
      2 by IL-1beta induced. COX-2 inhibitor reduced VEGF release by IL-1beta induced.
      CONCLUSIONS: i) In human ESC in vitro, IL-1beta up-regulated the COX-2 expression
      through the activation of p38 MAPK pathway, and not to COX-1. ii) Up-regulation
      of VEGF level by IL-1beta treatment was found in human endometriosis stromal cell
      and COX-2 inhibitor was involved in this process.

PMID- 24133592
TI  - Clinical significance of NOB1 expression in breast infiltrating ductal carcinoma.
AB  - BACKGROUND: NIN/RPN Binding protein 1 homologue (NOBp1), encoded by NOB1 gene,
      was reported to play an essential role in the oncogenesis and prognosis of
      carcinomas. We conducted a study to reveal its expression and clinical
      significance in breast infiltrating ductal carcinoma. METHODS: To explore the
      relationship between NOB1 expression and the clinical TNM (cTNM), 162 patients
      who undergone surgery were involved in the study. Compared to healthy tissues,
      abnormal localization and higher level of NOB1 in tumor cells was observed by
      Immunohistochemistry staining. Real-time PCR and western-blotting verified the up
      regulation of NOB1 in carcinoma individuals. RESULTS: A significant correlation
      between high level of NOB1 and the T stage, lymph node metastasis and cTNM was
      shown. Furthermore, patients with higher level of NOB1 predicted a declined
      overall survival (OS). Notably, multivariate analyses by Cox's proportional
      hazard model revealed that expression of NOB1 was an independent prognostic
      factor in breast infiltrating ductal carcinoma. CONCLUSIONS: In summary, our
      present study clarify that the aberrant expression of NOB1 in breast infiltrating
      ductal carcinoma is possibly involved with tumorigenesis and development, and the
      NOB1 protein could act as a potential biomarker for prognosis assessment of
      breast infiltrating ductal carcinoma. Related mechanism is worthy of further
      investigation.

PMID- 24133593
TI  - Expression of autophagy-related proteins in phyllodes tumor.
AB  - Phyllodes tumors (PTs) are classified as fibroepithelial tumors and their
      histologic grade is determined primarily by the features of the stromal
      component. In this study, we examined the expression profiles of autophagy
      related proteins in the stromal component of PTs and analyzed their clinical
      implications. We selected 204 human PT samples which were excised and diagnosed
      at Severance Hospital from 2000 to 2008 and created tissue microarray (TMA)
      blocks. Immunohistochemical assays for autophagy-related proteins (beclin-1,
      LC3A, LC3B, and p62) were then performed on these samples. The surgical specimens
      from higher grade PTs less frequently displayed cytoplasmic expression of beclin
      1, LC3A, LC3B, and p62 in the stromal component (p<0.001). In univariate
      analysis, the following profiles were associated with shorter disease-free
      survival and overall survival: nuclear beclin-1 positivity in the stromal
      component (p=0.013 and p=0.044, respectively), LC3A positivity in the stromal
      component (p<0.001 and p<0.001, respectively), and p62 positivity in the stromal
      component (p=0.012 and p=0.004, respectively). In conclusion, we determined that
      increased activity of autophagy-related proteins correlated with a higher
      histologic grade and poorer prognosis in PTs. These results lead us to conclude
      that the autophagy activity of the stromal cells plays a key role in the
      progression of PTs. 

PMID- 24133594
TI  - Pathogenesis and significance of glomerular C4d deposition in lupus nephritis:
      activation of classical and lectin pathways.
AB  - Immune complex-mediated complement activation through the classic pathway plays a
      key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal
      tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of
      the current study is to investigate the pathogenesis and clinicopathologic
      significance of glomerular C4d deposition in LN. We retrospectively analyzed
      clinical and histopathological data of 20 SLE patients with renal biopsy-proven
      LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying
      degrees of glomerular C4d staining associated with immune complex deposits, IgG
      (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d,
      C1q and C3 deposits in their glomeruli, indicative of the activation of the
      classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without
      accompanying C1q deposits, indicating the activation of the lectin pathway.
      Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In
      particular, a diffusely intense and coarsely granular pattern of C4d deposition
      in all glomeruli was detected in class V membranous LN. However, glomerular C4d
      deposition was correlated with neither disease activity of SLE nor histological
      activity and chronicity of LN. In conclusion, the activation of the lectin
      pathway as well as the classical pathway seems to play a crucial role in the
      pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class
      V membranous LN, although glomerular C4d deposition does not reflect SLE disease
      activity and histological activity and chronicity. 

PMID- 24133595
TI  - Detection of high-risk human papillomavirus subtypes in cervical glandular
      neoplasia by in situ hybridization.
AB  - In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect
      multiple high-risk human papillomavirus (HPV) subtypes in 27 cases of cervical
      adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results
      were compared with those of HPV detection by HPV-PCR genotyping and p16
      immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed HPV
      DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases
      (67%) by PCR. The concordance rate between HPV-ISH and HPV-PCR genotyping was 74%
      with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases,
      HPV-18 in 2 cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV
      PCR/genotyping, 22 cases (81.5%) were considered HPV positive.
      Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive;
      however, 4 of these cases were HPV-negative by both PCR and ISH. Combining HPV
      ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV
      detection in FFPE tissues from cervical glandular neoplasias. In contrast, p16
      immunohistochemistry seemed to have a low specificity for determining HPV status
      in cervical glandular neoplasia. HPV-ISH is useful for recognizing the
      distribution of HPV in AIS and CA tissues and visualizing signal patterns, and
      may be a useful tool to confirm the cervical origin of neoplasias and metastatic
      lesions. 

PMID- 24133596
TI  - Deep-seated huge hibernoma of soft tissue: a rare differential diagnosis of
      atypical lipomatous tumor/well differentiated liposarcoma.
AB  - BACKGROUND: Hibernoma is a rare benign fat-forming soft tissue tumor that
      differentiates similar to brown fat, hence an origin from remnants of fetal brown
      adipose tissue has been proposed. Mainly young adults are affected, usually
      without significant clinical symptoms. MATERIAL AND METHODS: We report on four
      patients with hibernomas, who were treated at our hospital during the last 10
      years. The clinicopathologic and immunohistochemical features are presented and
      treatment and follow-up data discussed. RESULTS: Patients were 2 women and 2 men
      aged 21-67 years (mean: 45 yrs) who presented with a slowly growing, painless
      mass. The anatomic location was the thigh, upper arm, lateral thoracic wall and
      paravertebral soft tissue. Two of them were diagnosed preoperatively through a
      percutaneous core needle biopsy and the other two underwent surgery because of
      high clinical and radiological suspicion of liposarcoma. The tumor's size ranged
      from 7 cm to 15.5 cm (mean: 11 cm). All were deep-seated subfascial intramuscular
      masses. Histologically, all four tumors were of the typical variant. All patients
      underwent a R0-surgical resection of the tumor and they were recurrence-free at
      last follow-up (mean: 47 months; range: 25-87). CONCLUSION: Hibernoma may present
      as huge deep intramuscular soft tissue mass in adults, closely mimicking well
      differentiated liposarcoma and should be considered in the differential diagnosis
      of fatty soft tissue tumors in any location. Surgical excision is the treatment
      of choice. The tumor has no malignant or recurrence potential.

PMID- 24133597
TI  - Elevated expression of SHIP2 correlates with poor prognosis in non-small cell
      lung cancer.
AB  - SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a vital regulator of
      phosphoinositide pools in metabolic pathways and is considered to downregulate
      phosphatidylinositol 3'-kinase signaling, which underlies the development of
      several kinds of human cancers. However, SHIP2 expression in non-small cell lung
      cancer (NSCLC) and its relationship with the clinical characteristics of NSCLC
      remain poorly understood. In this study, one-step quantitative reverse
      transcription-polymerase chain reaction and immunohistochemistry analysis with
      tissue microarray was used to evaluate SHIP2 expression in NSCLC and to
      investigate the relationship of this expression to NSCLC prognosis. Results
      showed that the expression of SHIP2 messenger RNA and protein was significantly
      higher in NSCLC than in corresponding non-cancerous tissues (both p < 0.05).
      SHIP2 protein expression in NSCLC was related to lymph node metastasis (p =
      0.042), TNM stage (p = 0.036), and 5-year survival rate (p = 0.046). The Kaplan
      Meier method and log-rank test suggested that high SHIP2 expression, tobacco
      consumption, and advanced tumor stage were significantly associated with low
      survival of NSCLC patients. The results of this research suggested that SHIP2
      expression was correlated with malignant phenotypes of NSCLC and may thus serve
      as a poor prognostic factor and valuable oncogene for NSCLC. 

PMID- 24133598
TI  - Clinicopathological features of acute promyelocytic leukemia: an experience in
      one institute emphasizing the morphological and immunophenotypic changes at the
      time of relapse.
AB  - Acute promyelocytic leukemia (APL) has two morphological variants, namely
      macrogranular (M3) and microgranular (M3v). M3v, characterized by the presence of
      neoplastic promyelocytes with only sparse fine azurophilic granules, accounts for
      10-25% of all APL and has unique biological characteristics. Relapse occurs in
      approximately 20% of patients with APL. The morphological type of the leukemic
      cells at relapse is usually identical with the primary disease, and only one case
      of morphological change at relapse has been reported. Here, we analyzed the
      clinicopathological features of APL, including 4 relapsed cases emphasizing
      morphological changes at the time of relapse. The unique finding of the present
      study is that 2 of 4 relapsed cases changed from M3 to M3v at relapse. The
      morphological features of these were different in each case (one had blastic
      features and the other resembled monocytoid leukemic cells). Cytogenetic analyses
      revealed the continued presence of t(15;17)(q22;q12) at the time of relapse and
      morphological change. Moreover, the immune phenotype of the leukemic cells
      changed from CD2(-)/CD34(-) to CD2(+)/CD34(+) at that time. These findings
      suggest that morphological change at relapse in APL may not be a rare event, and
      that the leukemic cells can show variable morphological features at the time of
      relapse, which could result in misdiagnosis as a different type of acute myeloid
      leukemia. Therefore, a comprehensive approach with emphasis on combined
      morphological, immunophenotypic, and cytogenetic analyses is important for
      diagnosis and appropriate treatment of relapsed APL. 

PMID- 24133600
TI  - Angiofibroma of soft tissue: clinicopathologic study of 2 cases of a recently
      characterized benign soft tissue tumor.
AB  - Angiofibroma of soft tissue is a very recently characterized, histologically
      distinctive benign mesenchymal neoplasm of unknown cellular origin composed of 2
      principal components, the spindle cell component and very prominent stromal
      vasculatures. It usually occurs in middle-aged adults, with a female
      predominance. Herein, we describe the clinical and pathologic details of 2 other
      examples of this benign tumor. Both patients were middle-aged male and presented
      with a slow-growing, painless mass located in the deep-seated soft tissue of
      thigh and left posterior neck region, respectively. Grossly, both tumors were
      well-demarcated, partial encapsulated of a grayish-white color with firm
      consistence. Histologically, one case showed morphology otherwise identical to
      those have been described before, whereas the other case showed in areas being
      more cellular than most examples of this subtype tumor had, with the lesional
      cells frequently exhibiting short fascicular, vaguely storiform and occasionally
      swirling arrangements, which posed a challenging differential diagnosis.
      Immunostains performed on both tumors did not confirm any specific cell
      differentiation with lesional cells only reactive for vimentin and focally desmin
      and negative for all the other markers tested. This report serves to broaden the
      morphologic spectrum of angiofibroma of soft tumor. Awareness of this tumor is
      important to prevent misdiagnosis as other more aggressive soft tissue tumor. 

PMID- 24133599
TI  - Maternal and neonatal outcomes in dichorionic twin pregnancies following IVF
      treatment: a hospital-based comparative study.
AB  - AIM: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously
      conceived dichorionic twin pregnancy. METHOD: We collected data regarding
      dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic
      sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as
      data regarding spontaneously conceived pregnancies (n=213) delivered after 28
      weeks of gestation at the Department of Obstetrics and Gynecology, Renmin
      Hospital in Wuhan in the years of 2010-2013. We then compared maternal and
      neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies,
      with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds
      ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were
      adjusted for maternal factors. RESULTS: The mean maternal age and the percentage
      of primiparous women were significantly higher in the IVF/ICSI group.
      Multivariate analysis revealed that maternal outcomes were comparable in both
      groups with/without adjustment for maternal age and parity. However, IVF/ICSI
      twins were less likely to have birth weight discordance than those spontaneously
      conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI
      0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF
      (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted
      OR=0.500, 95% CI 0.139-1.807). CONCLUSION: IVF/ICSI treatment was not a risk
      factor for adverse maternal neonatal outcomes, but the risk for birth weight
      discordance is lower among IVF/ICSI twins.

PMID- 24133601
TI  - Primary bone carcinosarcoma of the fibula with chondrosarcoma and squamous cell
      carcinoma components.
AB  - Carcinosarcoma is defined as a malignant neoplasm that is composed of both
      carcinomatous and sarcomatous components. The occurrence of carcinosarcoma in the
      bone is extremely rare. In this report, we describe the third documented de novo
      case of carcinosarcoma of the bone. A 59-year-old Japanese female presented with
      a painful tumor in her right lower leg. Plane radiography revealed an osteolytic
      destructive lesion with periosteal reaction and mineralization in the right
      fibula. Resection of the fibula tumor was performed under a clinical diagnosis of
      chondrosarcoma. Histopathological study revealed that the tumor was comprised of
      three components. The main component was proliferation of small round to short
      spindle cells (approximately 50%), and the remaining components were
      chondrosarcoma (30%) and squamous cell carcinoma (20%). Immunohistochemically,
      SOX9 was expressed in the small round to spindle cells and chondrosarcoma
      component, and p63 and p40 were expressed in all three components. Accordingly,
      an ultimate diagnosis of carcinosarcoma of the bone was made. The
      clinicopathological analysis of carcinosarcoma of the bone revealed that this
      type of tumor affects the middle-aged to elderly persons and occurs in the long
      bone. All three de novo cases had chondrosarcoma and squamous cell carcinoma
      components. One of the 3 patients died of the disease. The histogenesis of
      carcinosarcoma of the bone remains a matter of controversy, although a
      multpotential stem cell theory has been proposed. Additional studies are required
      to clarify the clinical behavior and histogenesis of carcinosarcoma of the bone. 

PMID- 24133602
TI  - Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma
      cell leukemia.
AB  - Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma
      cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or
      plasma cell myeloma, are typically characterized by production of a monoclonal
      heavy and/or light chain immunoglobulin. We present a case of a secondary plasma
      cell leukemia arising from plasma cell myeloma with dual expression of lambda and
      kappa light chains along with aberrant expression of CD33, CD20, and dim CD56.
      This case emphasizes the importance of recognizing aberrant immunophenotypes in
      plasma cell leukemias and represents the first reported case of biclonal light
      chain expression in a secondary plasma cell leukemia. 

PMID- 24133603
TI  - Desmoplastic fibroma of the scapula with fluorodeoxyglucose uptake on positron
      emission tomography: a case report and literature review.
AB  - We present a case of desmoplastic fibroma (DF) arising from the right scapula
      that was incidentally identified by fluorodeoxyglucose-positron emission
      tomography (FDG-PET) imaging performed to evaluate the presence of metastasis due
      to a history of surgical treatment for endometrioid adenocarcinoma. A 65-year-old
      woman was admitted to our hospital for consultation about a bone lesion in the
      right scapula although she was asymptomatic. FDG-PET revealed moderate focal
      (18)F-FDG uptake in the right scapula with a maximal standardized uptake value of
      3.2. The lower angle of the scapula was unclear on plain radiology. Needle biopsy
      was performed to make a differential diagnosis between primary bone and
      metastatic tumor. Pathologically, the tumor was composed of a relatively sparse
      proliferation of spindle-shaped fibroblastic/myofibroblastic cells in a dense
      collagenous background. Therefore, the diagnosis was a primary fibrous bone
      tumor. Wide excision was performed, because of the possibility of malignant
      tumors such as low-grade fibrosarcoma in light of the FDG-PET uptake.
      Pathologically, the resected tumor was composed of a proliferation of less
      atypical spindle cells in the collagenous stroma with focally myxoid change; no
      mitotic figures were observed. Immunohistochemically, beta-catenin
      nuclear/cytoplasmic staining was not observed, and no beta-catenin genetic
      mutations were detected. Therefore, the tumor was diagnosed as DF. DF is a tumor
      that exhibits FDG-PET uptake. There were no signs of recurrence 6 months after
      surgery. 

PMID- 24133604
TI  - Methotrexate-related Epstein-Barr virus-associated lymphoproliferative disorder
      occurring in the gingiva of a patient with rheumatoid arthritis.
AB  - It is well recognized that patients with immunodeficiency have a high risk of
      development of lymphoproliferative disorders (LPDs), and Epstein-Barr virus (EBV)
      is associated with the occurrence of LPDs. Methotrexate (MTX) is one of the
      common cause of iatrogenic-associated LPD, and approximately 40-50% of MTX
      related LPD cases occur in extranodal sites. However, the occurrence of MTX
      related LPD in the gingiva is extremely rare. Herein, we report the fourth
      documented case of MTX-related EBV-associated LPD occurring in the gingiva of a
      patient with rheumatoid arthritis (RA). A 76-year-old Japanese female with a 10
      year history of RA, who was treated with MTX and infliximab, presented with a
      tumorous lesion in the gingiva. Biopsy of the gingiva tumor revealed diffuse
      proliferation of large-sized lymphoid cells with cleaved nuclei containing
      conspicuous nucleoli. These lymphoid cells were CD20- and EBER-positive.
      Therefore, a diagnosis of MTX-related EBV-associated LPD showing features of
      diffuse large B-cell lymphoma (DLBCL) that occurred in the gingiva was made.
      Although the occurrence of LPD in the oral region, as seen in the present case,
      is rare, the prevalence of this disorder may be on the rise due to the increased
      number of patients undergoing immunosuppression therapy. Moreover,
      immunosenescence can also be a cause of EBV-associated LPD. Therefore,
      recognition of the occurrence of this disorder in the oral cavity and
      consideration of the clinical history can facilitate the correct diagnosis. 

PMID- 24133605
TI  - Xanthomatous meningioma: a case report with review of the literature.
AB  - Xanthomatous meningioma is an extremely rare variant of meningioma that is
      characterized histopathologically by the presence of tumor cells with lipid
      filled vacuolated cytoplasm. In this report, we describe the fifth documented
      case of xanthomatous meningioma and review its clinicopathological features. A 76
      year-old Japanese male presented with dizziness. Magnetic resonance imaging
      demonstrated a well-circumscribed tumor in the left parasagittal to frontal
      region with attachment of the dura mater. Histopathological examination of the
      resected specimen revealed proliferation of polygonal to spindle cells with
      eosinophilic cytoplasm and bland round to oval nuclei. Whorl formation and
      psammomas were scattered, and mitotic figures were rarely seen. A peculiar
      finding was the presence of extensive xanthomatous change continuing to the above
      mentioned typical meningothelial meningioma. These tumor cells had clear
      vacuolated cytoplasm and bland round to oval nuclei. Immunohistochemically,
      xanthomatous cells were positive for epithelial membrane antigen. Accordingly, an
      ultimate diagnosis of xanthomatous meningioma was made. Our clinicopathological
      analysis revealed that xanthomatous meningioma affects children to young persons
      or the elderly, and four of five cases were located in the supratentorial region.
      Although the detailed mechanism underlying the xanthomatous change has not been
      clarified, this change is thought to result from a metabolic abnormality of the
      neoplastic meningothelial cells. Further, xanthomatous change has also been
      reported in atypical and anaplastic meningiomas. Therefore, it is important to
      recognize that xanthomatous change can occur in meningiomas, and to avoid
      misidentifying these cells as macrophages. 

PMID- 24133606
TI  - Paraganglioma of the vulva: a case report and review of the literature.
AB  - Paraganglioma is a neuroendocrine neoplasm, which is extremely rare in the vulva
      and only one case has been reported. Here we present a case of vulvar
      paraganglioma in a 48-year-old woman and a literature review. The patient found a
      lump located in the genitals below the symphysis pubis 3 months before
      presentation when she complained that the lump was increasing in size. A 3.2 cm x
      2.3 cm x 1.5 cm nodule was excised from subcutaneous soft tissue in the vulva.
      Microscopy showed a diversity of cell morphologies and structures in the rich
      vascular network of the tumor separated the chief cells into round cell nests
      (Zellballen pattern). Some areas of the tumor presented epithelioid and spindle
      shaped cells with increased cell density and indistinct structural
      characteristics. Hyaline degeneration of collagen fibers or mucoid degeneration
      was found in tumor interstitium. Immunohistochemical staining showed diffused
      expression of synaptophysin in the chief cells, focal expression of S-100 protein
      in the sustentacular cells and high expression of CD34 in the vascular
      components. Based on morphological and immunohistochemical results, a rare
      paraganglioma of the vulva was diagnosed. 

PMID- 24133607
TI  - Malignant perivascular epithelioid cell tumor of the retroperitoneum.
AB  - Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal
      neoplasms characterized by a proliferation of perivascular cells with an
      epithelioid phenotype and expression of myo-melanocytic markers. The majority of
      PEComas seem to be benign and usually their prognosis is good. Malignant cases
      are extremely rare, exhibiting a malignant course with local recurrences and
      distant metastases. We herein report a case of a malignant PEComa arising in the
      retroperitoneum. The patient was a 55-year-old woman experiencing abdominal
      discomfort for approximately one month. Ultrasound and computer tomography (CT)
      scans of the abdomen revealed a solid mass arising from the retroperitoneum.
      Microscopically, the tumor was composed of epithelioid cells mixed with spindled
      cells. The nucleus had significant atypia, and the mitoses were obvious. The
      focal intravascular tumor embolus was visible. Immunohistochemically, the
      epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled
      tumor celLs were positive for SMA and desmin. Seven months after a surgical
      resection, an ultrasound revealed liver metastases. In conclusion, the malignant
      PEComas of the retroperitoneum is a very rare neoplasm with unique morphological
      and immunohistochemical characteristics. It should be differentiated from other
      epithelioid cell tumors of the retroperitoneum. 

PMID- 24133608
TI  - Synovial sarcoma of the neck masquerading as a malignant second branchial cleft
      cyst.
AB  - Synovial sarcoma is an uncommon, aggressive malignant tumor of the soft tissues
      primarily involving the extremities of young adults. Head and neck synovial
      sarcoma is rare, and its diagnosis and therapy are still challenging.We report a
      case of a young patient with synovial sarcoma, clinically masquerading as cystic
      mass of the neck and malignant second branchial cleft cyst. The pathological
      diagnosis of the sarcoma was confirmed by a multimodality diagnostic protocol,
      including histological, immunohistochemical and molecular genetic analysis. The
      patient underwent complete surgical excision followed by postoperative
      radiotherapy and recovered well. 

PMID- 24133609
TI  - Metastatic Crohn's disease accompanying granulomatous vasculitis and lymphangitis
      in the vulva.
AB  - Metastatic Crohn's disease (CD) is an extremely rare extragastrointestinal
      manifestation of CD, and is characterized histopathologically by the presence of
      non-caseating granulomatous inflammation. Granulomatous vasculitis and
      lymphangitis have rarely been documented in metastatic CD. Herein, we report the
      first documented case of metastatic CD accompanied by both granulomatous
      vasculitis and lymphangitis in the vulva. A 35-year-old Japanese female with CD
      presented with multiple small nodules in her vulva. Biopsy was performed under a
      clinical diagnosis of genital warts. A histopathological study revealed marked
      lymphangiectasia in the papillary dermis. Within the dilated lymphatics,
      lymphocytes and aggregates of macrophages were present, which are typical
      features of granulomatous lymphangitis. Tiny non-caseating granulomas and
      granulomatous vasculitis were also observed. Accordingly, a diagnosis of
      metastatic CD accompanied by both granulomatous vasculitis and lymphangitis was
      made. The occurrence of cutaneous lesions in patients with CD is well known.
      Albeit extremely rare, lymphangiectasia has been reported in the vulva of CD
      patients that clinically mimicked viral warts, as in the present case. The
      diagnosis of metastatic CD in the present case was not difficult because
      characteristic histopathological features were present, and a clinical history of
      CD was available. However, a few cases of genital swelling associated with
      granulomatous inflammation prior to a diagnosis of gastrointestinal CD have been
      documented. Therefore, granulomatous vasculitis and lymphangitis in the external
      genitals should be considered as potential indication of metastatic CD even in
      cases without a history of gastrointestinal CD. 

PMID- 24133610
TI  - Encephalomalacic dysplastic mass lesion associated with vascular abnormalities in
      an elderly man. Is this "acquired" focal cortical dysplasia?
AB  - Focal cortical dysplasia (FCD) is known to occur in association with a principal
      lesion and has been newly introduced as FCD type III in the ILAE 2011
      classification system of FCDs. FCD type IIIc is associated with vascular
      malformations, and in all such cases in the literature with histologic
      confirmation, the principal lesion was a cavernous angioma. We present here a
      case of mass-forming FCD type IIIc with very unusual vasculopathies. The patient,
      a 75-year-old man, presented with a seizure and left-sided weakness. MRI showed a
      right frontal intra-axial mass (4 cm in diameter). He had significant multiple
      cardiovascular risk factors and a history of melanoma and bladder cancer.
      Craniotomy was performed for excision of the suspected neoplasm. Histologically,
      the cortex showed transition from normal, laminar cortical architecture to marked
      architectural abnormality with irregular areas of encephalomalacia, with
      intervening, almost nodular regions of "preserved" cortex. These regions
      consisted of large clusters of dysplastic and maloriented neurons. There were
      medium-sized to larger arteries with marked medial thickening and luminal
      stenosis, predominantly within the markedly thickened and fibrosed leptomeninges.
      In addition, the parenchymal vessels showed markedly hyalinized and thickened
      walls, and several exhibited glomeruloid clusters of new capillaries. We
      interpreted the cortical and subcortical encephalomalacic features to be
      presumably "secondary" to the underlying/associated vascular pathology. This case
      may represent "acquired" FCD. It is possible that this patient had a preexistent
      cortical dysplasia with secondary ischemic changes; however, given the absence of
      previous history of seizure, this appears less likely. 

PMID- 24133612
TI  - Combined effects of food and exercise on anaphylaxis.
AB  - Food-dependent exercise-induced anaphylaxis (FDEIAn) is induced by different
      types and various intensities of physical activity, and is distinct from food
      allergies. It has been shown that consumption of allergenic food followed by
      exercise causes FDEIAn symptoms. Intake of allergenic food or medication before
      exercise is a major predisposing factor for FDEIAn. Urticaria and severe allergic
      reactions are general symptoms of FDEIAn. Dermatological tests and serum IgE
      assays are the typical prescreening methods, and have been used for several
      decades. However, these screening tests are not sufficient for detecting or
      preventing FDEIAn. It has been found that exercise may stimulate the release of
      mediators from IgE-dependent mast cells that can result in FDEIAn when a certain
      threshold level has been exceeded. Mast cell degradation might be a major factor
      to induce FDEIAn but this has not been determined. A number of foods have been
      reported to be involved in the onset of FDEIAn including wheat, eggs, chicken,
      shrimp, shellfish, nuts, fruits, and vegetables. It is also known that aspirin
      increases the occurrence of type I allergy symptoms when combined with specific
      foods. Moreover, high intensity and frequent exercise are more likely to provoke
      an attack than low intensity and less frequent exercise. In this paper, we
      present the current views of the pathophysiological mechanisms underlying FDEIAn
      within the context of exercise immunology. We also present a detailed FDEIAn
      definition along with etiologic factors and medical treatment for cholinergic
      urticaria (UC) and exercise-induced anaphylaxis (EIA). 

PMID- 24133611
TI  - Cavernous hemangioma of the parietal bone.
AB  - PATIENT: Male, 38 FINAL DIAGNOSIS: Cavernous hemangioma Symptoms: Headache *
      parietal mass MEDICATION: - Clinical Procedure: - Specialty: Neurosurgery.
      OBJECTIVE: A rare disease. BACKGROUND: Bone hemangioma is a vascular hemartoma of
      bone structures. In general, this pathology is detected on incidentally
      investigated patients' films. Bone hemangioma is most commonly seen in 4(th)
      decade of life and the male/female ratio is 1/1.5. The locations of these lesions
      are commonly long bones of the vertebral column and the skull. Primary bone
      hemangiomas constitute less than 1% of all bone tumors, and they are seen at 0.2%
      in the calvarial region. CASE REPORT: Cases with this pathology are seen on
      incidental radiological evaluations. We report the case of a 38-year-old man with
      localized headache and a palpable mass in the left parietal region, admitted and
      operated on after cranial CT and MRI. Pathology investigation revealed a
      cavernous hemangioma. CONCLUSIONS: We suspected that in our case head trauma may
      have been the cause of cavernous hemangioma in the calvarial region, because
      cavernous hemangiomas are rarely located there. Localized headache and minor
      discomfort can be seen with this pathology. The best treatment for cavernous
      hemangiomas is the removal of the mass within the limits of safe surgery.

PMID- 24133613
TI  - Impact of Korean pine nut oil on weight gain and immune responses in high-fat
      diet-induced obese mice.
AB  - Korean pine nut oil (PNO) has been reported to have favorable effects on lipid
      metabolism and appetite control. We investigated whether PNO consumption could
      influence weight gain, and whether the PNO-induced effect would result in an
      improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6
      mice were fed control diets with 10% energy fat from either PNO or soybean oil
      (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or
      SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative
      responses of splenocytes upon stimulation with concanavalin A (Con A) or
      lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and
      interferon (IFN)-gamma, and LPS-stimulated production of IL-6, IL-1beta, and
      prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs
      containing PNO resulted in significantly less weight gain (17% less, P < 0.001),
      and lower weight gain was mainly due to less white adipose tissue (18% less, P =
      0.001). The reduction in weight gain did not result in the overall enhancement in
      splenocyte proliferation. Overall, PNO consumption resulted in a higher
      production of IL-1beta (P = 0.04). Replacement of SBO with PNO had no effect on
      the production of IL-2, IFN-gamma, IL-6, or PGE2 in mice fed with either the
      control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in
      mice fed with HFD, but this effect did not result in the overall improvement in
      immune responses. 

PMID- 24133614
TI  - In vivo antioxidant, hypoglycemic, and anti-tumor activities of anthocyanin
      extracts from purple sweet potato.
AB  - Anthocyanin from purple sweet potato (PSP) extracted by microwave baking (MB) and
      acidified electrolyzed water (AEW) exhibited antioxidant activity. After further
      purification by macroporous AB-8 resin, the color value of PSP anthocyanin (PSPA)
      reached 30.15 with a total flavonoid concentration of 932.5 mg/g. The purified
      extracts had more potent antioxidant activities than the crude extracts. After
      continuously administering the PSP extracts to 12-mo-old mice for 1 mo, the anti
      aging index of the experimental group was not significantly different from that
      of 5-mo-old mice. To a certain degree, PSPA was also effective for controlling
      plasma glucose levels in male Streptozocin (STZ)-treated diabetic mice. In
      addition, the extracts inhibited Sarcoma S180 cell growth in ICR mice. Mice
      consuming the PSP extracts formed significantly fewer and smaller sarcomas than
      mice consuming the control diets. The highest inhibition rate was 69.03%. These
      results suggest that anthocyanin extracts from PSP not only exert strong
      antioxidant effects in vitro, but also had anti-aging, anti-hyperglycemic, and
      anti-tumor activities. 

PMID- 24133615
TI  - Effect of green tea extract microencapsulation on hypertriglyceridemia and
      cardiovascular tissues in high fructose-fed rats.
AB  - The application of polyphenols has attracted great interest in the field of
      functional foods and nutraceuticals due to their potential health benefits in
      humans. However, the effectiveness of polyphenols depends on their bioactivity
      and bioavailability. In the present study, the bioactive component from green tea
      extract (GTE) was administrated orally (50 mg/kg body weight/day) as free or in a
      microencapsulated form with maltodextrin in rats fed a high fructose diet. High
      fructose diet induced features of metabolic syndrome including
      hypertriglyceridemia, hyperuricemia, increased serum total cholesterol, and
      retroperitoneal obesity. In addition, myocardial fibrosis was increased. In rats
      receiving high fructose diet, the lowering of blood triglycerides, total
      cholesterol, non esterified fatty acid (NEFA) and uric acid, as well as the
      reduction in final body weight and retroperitoneal fat weight associated with the
      administration of GTE, led to a reversal of the features of metabolic syndrome (P
      < 0.05). In particular, the administration of microencapsulated GTE decreased
      myocardial fibrosis and increased liver catalase activity consistent with a
      further alleviation of serum NEFA, and hyperuricemia compared to administration
      of GTE. Taken together, our results suggest that microencapsulation of the
      bioactive components of GTE might have a protective effect on cardiovasucular
      system by attenuating the adverse features of myocardial fibrosis, decreasing
      uric acid levels and increasing hepatic catalase activity effectively by
      protecting their bioactivities. 

PMID- 24133616
TI  - Effect of onion peel extract supplementation on the lipid profile and
      antioxidative status of healthy young women: a randomized, placebo-controlled,
      double-blind, crossover trial.
AB  - The consumption of fruits and vegetables that have high polyphenol content has
      been previously associated with a reduced risk for cardiovascular disease. We
      investigated the effects of onion peel extract on plasma total antioxidant
      capacity, lipid peroxidation, and leukocyte DNA damage. This study was a
      randomized, double-blind, placebo-controlled, crossover trial. Healthy female
      subjects received either onion peel extract or placebo (dextrin) for two weeks,
      underwent a 1-week washout period, and then received the other treatment for an
      additional two weeks. After two weeks of onion peel extract supplementation, the
      total cholesterol level, low-density lipoprotein cholesterol level, and
      atherogenic index significantly decreased (P < 0.05). No changes were observed in
      activities of erythrocyte antioxidant enzymes or levels of lipid peroxidation
      markers following onion peel extract supplementation. Additionally, no
      significant difference was found in plasma antioxidant vitamin (retinol,
      tocopherols, carotenoids, and coenzyme Q10) levels or ex vivo H2O2-provoked
      oxidative DNA damage after onion peel extract supplementation. The present
      interventional study provides evidence of the health benefits of onion peel
      extract and demonstrates its effects in modulating lipid profiles in healthy
      young Korean women. 

PMID- 24133617
TI  - Dietary zinc intake is inversely associated with systolic blood pressure in young
      obese women.
AB  - Zinc may participate in blood pressure regulation and in the pathogenesis of
      hypertension. The study examined the relationship between zinc status and blood
      pressure in obese Korean women. Forty obese women (body mass index (BMI) >= 25
      kg/m(2)) aged 19-28 years participated in this study. Zinc intake was estimated
      from one 24 hour recall and 2-day diet records. Serum and urinary zinc
      concentrations were determined by atomic absorbance spectrophotometry. Systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) were measured using an
      automatic sphygmometer. Metabolic variables, such as waist circumference,
      triglyceride, high density lipoprotein (HDL) cholesterol, fasting glucose, and
      fasting insulin, were also measured. Dietary zinc intake of obese women was
      averagely 7.5 mg/day. Serum zinc and urinary zinc concentrations were 13.4 umol/L
      and 378.7 ug/day, respectively. Averages of SBP and DBP were 119 mmHg and 78
      mmHg. Dietary zinc intake was negatively correlated with SBP after adjusting for
      energy intake (P < 0.05), but serum and urinary zinc concentrations were not
      found to be correlated with SBP or DBP. Multivariate linear regression analysis
      showed that dietary zinc intake was inversely associated with SBP in obese women
      after adjusting for body weight, energy intake and sodium intake (P = 0.0145).
      The results show that dietary zinc intake may be an independent risk factor of
      elevated SBP in obese Korean women. 

PMID- 24133618
TI  - The effect of low glycemic index diet on body weight status and blood pressure in
      overweight adolescent girls: a randomized clinical trial.
AB  - Although several studies have assessed the influence of the glycemic index on
      body weight and blood pressure among adults, limited evidence exists for the
      pediatric age population. In the current study, we compared the effects of low
      glycemic index (LGI) diet to the healthy nutritional recommendation (HNR)-based
      diet on obesity and blood pressure among adolescent girls in pubertal ages. This
      10-week parallel randomized clinical trial comprised of 50 overweight or obese
      and sexually mature girls less than 18 years of age years, who were randomly
      assigned to LGI or HNR-based diet. Macronutrient distribution was equivalently
      prescribed in both groups. Blood pressure, weight and waist circumference were
      measured at baseline and after intervention. Of the 50 participants, 41 subjects
      (include 82%) completed the study. The GI of the diet in the LGI group was 42.67
      +/- 0.067. A within-group analysis illustrated that in comparison to the baseline
      values, the body weight and body mass index (not waist circumference and blood
      pressure) decreased significantly after the intervention in both groups (P =
      0.0001). The percent changes of the body weight status, waist circumference and
      blood pressure were compared between the two groups and the findings did not show
      any difference between the LGI diet consumers and those in the HNR group. In
      comparison to the HNR, LGI diet could not change the weight and blood pressure
      following a 10-week intervention. Further longitudinal studies with a long-term
      follow up should be conducted in this regard. 

PMID- 24133619
TI  - Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of
      soy products with different aglycone/glucoside ratios in South Korean women.
AB  - Asian populations are thought to receive significant health benefits from
      traditional diets rich in soybeans due to high isoflavone contents. However,
      available epidemiologic data only weakly support this hypothesis. The present
      study was carried out to assess the pharmacokinetics of isoflavones in South
      Korean women after ingestion of soy-based foods. Twenty-six healthy female
      volunteers (20-30 y old) consumed three different soy products (i.e., isogen,
      soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma
      and urine isoflavone concentrations were measured by high-performance liquid
      chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic
      parameters were determined using the WinNonlin program. The area under the curve
      (AUC) for plasma daidzein levels of the soymilk group (2,101 +/- 352 ng . h/mL)
      was significantly smaller than those of the isogen (2,628 +/- 573 ng . h/mL) and
      fermented soybean (2,593 +/- 465 ng . h/mL) groups. The maximum plasma
      concentration (Cmax ) of daidzein for the soymilk group (231 +/- 44 ng/mL) was
      significantly higher than those of the isogen (160 +/- 32 ng/mL) and fermented
      soybean (195 +/- 35 ng/mL) groups. The half-lives of daidzein and genistein in
      the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than
      those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented
      soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and
      genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented
      soybean group, and 33% and 22% for the soymilk group. In conclusion, our data
      indicated that soy products containing high levels of isoflavone aglycone are
      more effective for maintaining plasma isoflavone concentrations. Additional dose
      response, durational, and interventional studies are required to evaluate the
      ability of soy-based foods to increase the bioavailability of isoflavones that
      positively affect human health. 

PMID- 24133620
TI  - Maternal and grandmaternal obesity and environmental factors as determinants of
      daughter's obesity.
AB  - Obesity may be the consequence of various environmental or genetic factors, which
      may be highly correlated with each other. We aimed to examine whether
      grandmaternal and maternal obesity and environmental risk factors are related to
      obesity in daughters. Daughters (n = 182) recruited from female students, their
      mothers (n = 147) and their grandmothers (n = 67) were included in this study.
      Multivariable logistic regression was used to analyze the association between the
      daughter's obesity and maternal, grandmaternal, and environmental factors.
      Maternal heights of 161-175cm (OD: 8.48, 95% CI: 3.61-19.93) and 156-160 cm
      (2.37, 1.14-4.91) showed positive associations with a higher height of daughter,
      compared to those of 149-155 cm. Mothers receiving a university or a higher
      education had a significant OR (3.82, 1.27-11.50) for a higher height of daughter
      compared to those having a low education (elementary school). Mother having the
      heaviest weight at current time (59-80 kg, 3.78, 1.73-8.28) and the heaviest
      weight at 20 years of age (51-65 kg, 3.17, 1.53-6.55) had significant
      associations with a higher height of daughters, compared to those having the
      lightest weight at the same times. There was no association between the height,
      weight, and BMI of daughters and the characteristics and education of her
      grandmothers. In conclusion, although genetic factors appear to influence the
      daughter's height more than environmental factors, the daughter's weight appears
      to be more strongly associated with individual factors than the genetic factors. 

PMID- 24133621
TI  - Effects of calcium intake, milk and dairy product intake, and blood vitamin D
      level on osteoporosis risk in Korean adults: analysis of the 2008 and 2009 Korea
      National Health and Nutrition Examination Survey.
AB  - This study was performed to determine the effects of dietary calcium (Ca) intake,
      milk and dairy product intake, and serum vitamin D level on bone mineral density.
      The survey data from the 2008-2009 Korea National Health and Nutrition
      Examination Survey (KNHANES) for adults (3,819 males, 5,625 females) aged > 20
      years were examined; osteoporosis was defined according to the standards for
      Asian populations (T-score < -2.5). The risk for osteoporosis significantly
      decreased as Ca intake increased; this effect persisted (quartile 4 vs. quartile
      1 of Ca intake: odds ratio [OR] 0.66; 95% confidence interval [CI]: 0.50-0.87)
      even after adjustment for gender, age, and other factors (body mass index, serum
      vitamin D, menstruation, female hormone intake, menopausal status, and the number
      of days per week of muscular strength exercise). Additionally, the risk for
      osteoporosis significantly decreased as the Ca/P ratio increased (quartile 4 vs.
      quartile 1: OR 0.76; 95% CI: 0.58-0.98). The degree of risk was 0.96 (0.66-1.38)
      in those who consumed < 1 portion of milk or dairy products daily, and 0.71 (0.53
      0.96) in those who consumed > 1 portion per day, compared with those who had zero
      intake. The risk for osteoporosis significantly decreased as the serum 25(OH)
      vitamin D level increased. From these results, we advocate an increase in Ca,
      milk, and dairy product intake, and that serum 25(OH) vitamin D levels be
      maintained within the normal range, for the maintenance of bone health and the
      prevention of osteoporosis in adults. 

PMID- 24133622
TI  - Overexpression of DRAM enhances p53-dependent apoptosis.
AB  - Tumor suppressor p53-dependent apoptosis is thought to be one of the most
      important tumor-suppressive mechanisms in human tumorigenesis. Till date, "super
      p53" mutants exhibiting more potent ability to induce apoptosis than wild-type
      p53 have been reported. These super p53s may provide a clue for development of
      novel therapeutic targets. However, the major mechanism underlying the super p53
      dependent apoptosis remains unclear. To identify critical gene(s) in this
      mechanism, we performed a comprehensive and comparative expression analysis in
      p53-null Saos-2 cells with conditional expression of wild-type p53 and S121F,
      which was previously reported as a super p53 mutant. We identified damage
      regulated autophagy modulator (DRAM) as one of the genes that were more
      upregulated by S121F than wild-type p53. Although knockdown of DRAM was not
      sufficient for reducing the ability of S121F to induce apoptosis, DRAM
      overexpression enhanced the ability in a wild-type p53-dependent manner. Here, we
      show that DRAM is an important gene for the enhancement of p53-dependent
      apoptosis. Additional analysis of the mechanism of super p53-dependent apoptosis
      may lead to the identification of novel drug targets for cancer therapy.

PMID- 24133623
TI  - Optimization of routine KRAS mutation PCR-based testing procedure for rational
      individualized first-line-targeted therapy selection in metastatic colorectal
      cancer.
AB  - KRAS mutation detection represents a crucial issue in metastatic colorectal
      cancer (mCRC). The optimization of KRAS mutation detection delay enabling
      rational prescription of first-line treatment in mCRC including anti-EGFR
      targeted therapy requires robust and rapid molecular biology techniques. Routine
      analysis of mutations in codons 12 and 13 on 674 paraffin-embedded tissue
      specimens of mCRC has been performed for KRAS mutations detection using three
      molecular biology techniques, that is, high-resolution melting (HRM), polymerase
      chain reaction restriction fragment length polymorphism (PCR-RFLP), and allelic
      discrimination PCR (TaqMan PCR). Discordant cases were assessed with COBAS 4800
      KRAS CE-IVD assay. Among the 674 tumor specimens, 1.5% (10/674) had excessive DNA
      degradation and could not be analyzed. KRAS mutations were detected in 38.0%
      (256/674) of the analysable specimens (82.4% in codon 12 and 17.6% in codon 13).
      Among 613 specimens in whom all three techniques were used, 12 (2.0%) cases of
      discordance between the three techniques were observed. 83.3% (10/12) of the
      discordances were due to PCR-RFLP as confirmed by COBAS 4800 retrospective
      analysis. The three techniques were statistically comparable (kappa > 0.9; P <
      0.001). From these results, optimization of the routine procedure consisted of
      proceeding to systematic KRAS detection using HRM and TaqMan and PCR-RFLP in case
      of discordance and allowed significant decrease in delays. The results showed an
      excellent correlation between the three techniques. Using HRM and TaqMan warrants
      high-quality and rapid-routine KRAS mutation detection in paraffin-embedded tumor
      specimens. The new procedure allowed a significant decrease in delays for
      reporting results, enabling rational prescription of first-line-targeted therapy
      in mCRC.

PMID- 24133624
TI  - Gene expression of the IGF pathway family distinguishes subsets of
      gastrointestinal stromal tumors wild type for KIT and PDGFRA.
AB  - Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of
      Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal
      tract. While the majority of GISTs harbor activating mutations in either the v
      kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet
      derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10
      15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These "wild
      type" GISTs have been reported to express high levels of the insulin-like growth
      factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being
      evaluated in clinical trials. However, it is not clear that all wild-type GISTs
      express IGF1R, because studies to date have predominantly focused on a particular
      subtype of gastric wild-type GIST that is deficient in the mitochondrial
      succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs,
      including 72 wild-type specimens, was therefore undertaken to further
      characterize wild-type GIST subtypes based on the relative expression of
      transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were
      also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and
      insulin receptor [INSR]), neural markers (CDH2[CDH: Cadherin], neurofilament,
      light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE
      like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B
      protein expression was also assessed as a measure of SDH complex integrity. In
      addition to the previously described SDH-deficient, IGF1R(high) wild-type GISTs,
      other SDH-intact wild-type subpopulations were defined by high relative
      expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with
      high IGF2. These results underscore the complexity and heterogeneity of wild-type
      GISTs that will need to be factored into molecularly-targeted therapeutic
      strategies.

PMID- 24133625
TI  - Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK
      and mTOR inhibitions in renal cancer cells.
AB  - Advanced renal cell carcinoma (RCC) remains an incurable disease, and newer
      anticancer drugs are needed. Bisebromoamide, a novel cytotoxic peptide, was
      isolated from the marine cyanobacterium Lyngbya species at our laboratory in
      2009. This compound specifically inhibited the phosphorylation of ERK in platelet
      derived growth factor-activated normal rat kidney cells. The aim of this study
      was to evaluate the effect and elucidate the potential mechanism of
      Bisebromoamide actions on human RCC cells. Two renal cancer cell lines, 769-P and
      786-O, were used. The effects of Bisebromoamide were analyzed employing assays
      for water-soluble Tetrazolium-1 salts. Apoptosis was determined by flow
      cytometric TUNEL analysis. Cell-cycle distributions were analyzed by flow
      cytometry using BrdU/propidium iodide (PI) staining. Kinases of the
      phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR)
      pathway and Raf/MEK/ERK pathway were analyzed by Western blotting. After
      Bisebromoamide treatment for 48 and 72 h, cell viability was significantly
      decreased in both cell lines at 1 and 10 MUmol/L. After treatment with 1 MUmol/L
      Bisebromoamide for 72 h, apoptosis and the increased percentage of cells in the
      sub-G1 phase were observed in both cell lines. Bisebromoamide inhibited the
      phosphorylation of ERK and Akt in both cell lines tested. Similar effects were
      demonstrated for phosphorylation of mTOR and p70 S6. Bisebromoamide is a
      promising potential agent against RCC due to its ability to inhibit both the
      Raf/MEK/ERK and PI3K/Akt/mTOR pathways.

PMID- 24133626
TI  - Targeting phosphodiesterase 3B enhances cisplatin sensitivity in human cancer
      cells.
AB  - We previously reported that human squamous cell carcinoma (SCC) cell lines
      refractory to cis-diaminedichloro-platinum II (cisplatin [CDDP]) had significant
      upregulation of the phosphodiesterase 3B gene (PDE3B), suggesting that inhibiting
      PDE3B suppresses CDDP resistance. shRNA-mediated PDE3B depletion in CDDP
      resistant cells derived from SCC cells and Hela cells and induced CDDP
      sensitivity and inhibited tumor growth with elevated cyclic GMP induction
      resulting in upregulation of the multidrug-resistant molecule, but this did not
      occur in the 5-fluorouracil-resistant hepatocellular carcinoma cell lines.
      Furthermore, the antitumor growth effect of the combination of a PDE3B inhibitor
      (cilostazol) and CDDP in vivo was also greater than with either cilostazol or
      CDDP alone, with a significant increase in the number of apoptotic and cell
      growth-suppressive cancer cells in CDDP-resistance cell lines. Our results
      provided novel information on which to base further mechanistic studies of CDDP
      sensitization by inhibiting PDE3B in human cancer cells and for developing
      strategies to improve outcomes with concurrent chemotherapy.

PMID- 24133627
TI  - Preventive effects of low-dose aspirin on colorectal adenoma growth in patients
      with familial adenomatous polyposis: double-blind, randomized clinical trial.
AB  - There are several reports of clinical trials of aspirin in sporadic colon cancer.
      However, only one double-blind trial of aspirin in patients with familial
      adenomatous polyposis (FAP) has been reported to date. This double-blind,
      randomized, placebo-controlled clinical trial was therefore performed to evaluate
      the influence of low-dose aspirin enteric-coated tablets (100 mg/day for 6-10
      months) in 34 subjects with FAP (17 each in the aspirin and placebo groups). The
      increase in mean diameter of colorectal polyps tended to be greater in the
      placebo group compared with the aspirin group, which showed a response ratio,
      that is, aspirin response rate (number of subjects with reduced
      polyps/total)/placebo response rate (number of subjects with reduced
      polyps/total), of 2.33 (95% confidence interval: 0.72-7.55). Subgroup analysis
      revealed that the number of subjects with a mean baseline polyp diameter of <=2
      mm, and the diameter and number of polyps after intervention showed a significant
      reduction in the aspirin group. Adverse effects of aspirin, such as anastomotic
      ulcer, aphtha in the large intestine, and progression of anemia, occurred in
      three subjects. Moreover, none of the subjects developed colorectal cancer. The
      results thus indicated a potential for aspirin to reduce colorectal adenoma
      development in patients with FAP, but careful follow-up is needed to avoid or
      rapidly counter severe adverse effects.

PMID- 24133628
TI  - Anti-human-cytomegalovirus immunoglobulin G levels in glioma risk and prognosis.
AB  - The role of human cytomegalovirus (HCMV) in glioma development and progression
      remains controversial. The purpose of our study was to assess the potential
      associations between anti-HCMV antibodies (immunoglobulin G [IgG] and
      immunoglobulin M [IgM]) and glioma risk and prognosis using data from the Harris
      County Case-Control Study. Multivariable logistic regression models were utilized
      to estimate odds ratios and 95% confidence intervals (CI) for the associations
      between glioma status and antibody levels among glioma cases (n = 362) and cancer
      free controls (n = 462). Hazard ratios and 95% CIs were calculated using Cox
      proportional hazards regression, adjusting for age, race, and sex, to determine
      if antibody levels were associated with survival over time among cases. Among IgG
      positive participants, increasing anti-HCMV IgG levels were associated with
      decreasing glioma risk (P for trend = 0.0008), and those with the lowest level of
      anti-HCMV IgG (<10 U/mL) had the highest glioma risk, controlling for age, sex,
      and race/ethnicity (OR: 2.51, 95% CI: 1.42-4.43). Antibody levels were not
      associated with survival among glioma cases. Our study contributes new evidence
      toward the potential importance of the direct and indirect effects of HCMV
      infection in gliomagenesis.

PMID- 24133629
TI  - Early detection of clinically significant prostate cancer at diagnosis: a
      prospective study using a novel panel of TMPRSS2:ETS fusion gene markers.
AB  - We explore noninvasive clinical applications of multiple disease-specific fusion
      markers recently discovered in prostate cancer to predict the risk of cancer
      occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate
      specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled
      for this study. Prospectively collected urine was blind coded for laboratory
      tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS
      fusion markers with a sensitive quantitative PCR platform. The pathology reported
      39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique
      combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples.
      A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified
      with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on
      biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3
      and serum PSA, a regression model was developed to predict biopsy outcomes with
      an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS)
      was shown to be an independent predictor to the high-grade cancer, with a
      predictive accuracy of 80% when coupled with PSA density. The individualized risk
      scores further stratified a high-risk group that is composed of 92% high-grade
      cancers and a low-risk group that harbors mainly clinically insignificant
      cancers. In conclusion, we have identified a novel combination of fusion types
      very specific to the clinically significant prostate cancer and developed
      effective regression models to predict biopsy outcomes and aggressive cancers at
      diagnosis.

PMID- 24133630
TI  - Targeting hyperactivation of the AKT survival pathway to overcome therapy
      resistance of melanoma brain metastases.
AB  - Brain metastases are the most common cause of death in patients with metastatic
      melanoma, and the RAF-MEK-ERK and PI3K-AKT signaling pathways are key players in
      melanoma progression and drug resistance. The BRAF inhibitor vemurafenib
      significantly improved overall survival. However, brain metastases still limit
      the effectiveness of this therapy. In a series of patients, we observed that
      treatment with vemurafenib resulted in substantial regression of extracerebral
      metastases, but brain metastases developed. This study aimed to identify factors
      that contribute to treatment resistance in brain metastases. Matched brain and
      extracerebral metastases from melanoma patients had identical ERK, p-ERK, and AKT
      immunohistochemistry staining patterns, but there was hyperactivation of AKT (p
      AKT) and loss of PTEN expression in the brain metastases. Mutation analysis
      revealed no differences in BRAF, NRAS, or KIT mutation status in matched brain
      and extracerebral metastases. In contrast, AKT, p-AKT, and PTEN expression was
      identical in monolayer cultures derived from melanoma brain and extracerebral
      metastases. Furthermore, melanoma cells stimulated by astrocyte-conditioned
      medium showed higher AKT activation and invasiveness than melanoma cells
      stimulated by fibroblast-conditioned medium. Inhibition of PI3K-AKT signaling
      resensitized melanoma cells isolated from a vemurafenib-resistant brain
      metastasis to vemurafenib. Brain-derived factors appear to induce hyperactivation
      of the AKT survival pathway and to promote the survival and drug resistance of
      melanoma cells in the brain. Thus, inhibition of PI3K-AKT signaling shows
      potential for enhancing and/or prolonging the antitumor effect of BRAF inhibitors
      or other anticancer agents in melanoma brain metastases.

PMID- 24133631
TI  - A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy
      for hepatocellular carcinoma.
AB  - Cisplatin (CDDP) is an anticancer agent that is commonly used in hepatic arterial
      infusion (HAI) chemotherapy for hepatocellular carcinoma (HCC). This study aimed
      to clarify the safe and effective dose of CDDP in HAI for HCC. The hypervascular
      area was measured in 42 HCCs before and after HAI with CDDP. Serum platinum
      concentration was quantified in the peripheral and/or middle hepatic veins by
      atomic absorption spectrometry. The relation between the HCC response and CDDP
      dose was statistically analyzed. The multiple HCC nodules in an individual case
      generally demonstrated the same response to CDDP. The free-platinum concentration
      stayed relatively constant in the hepatic vein during HAI followed by a rapid
      decline, while total-platinum gradually increased then slowly disappeared over
      several days. After CDDP-HAI, 15 HCCs shrunk and 27 HCCs grew. The reduction rate
      in the shrunken nodules was tended to be correlated with CDDP dose after
      standardization with the target liver volume. On the other hand, the growth rate
      of the enlarged HCCs was significantly correlated with CDDP dose after
      normalization with creatinine clearance. These data support a recommendation of
      CDDP-HAI infusion where the amount of CDDP (mg) administered is less than patient
      creatinine clearance (mL/min/1.73 m(2)) upon an assumption of HCC doubling time
      of 90 days, and the targeted liver is smaller than 200 times the CDDP dose (mg).
      A further analysis is required to define appropriate injection speeds.

PMID- 24133633
TI  - NF-kappaB inhibitor could be a novel treatment for multiple myeloma.

PMID- 24133632
TI  - Metformin use and improved response to therapy in rectal cancer.
AB  - Locally advanced rectal cancer is commonly treated with chemoradiation prior to
      total mesorectal excision (TME). Studies suggest that metformin may be an
      effective chemopreventive agent in this disease as well as a possible adjunct to
      current therapy. In this study, we examined the effect of metformin use on
      pathologic complete response (pCR) rates and outcomes in rectal cancer. The
      charts of 482 patients with locally advanced rectal adenocarcinoma treated from
      1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was
      50.4 Gy (range 19.8-63). Nearly, all patients were treated with concurrent 5
      fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%).
      Patients were categorized as nondiabetic (422), diabetic not taking metformin
      (40), or diabetic taking metformin (20). No significant differences between
      groups were found in clinical tumor classification, nodal classification, tumor
      distance from the anal verge or circumferential extent, pretreatment
      carcinoembryonic antigen level, or pathologic differentiation. pCR rates were
      16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for
      diabetics taking metformin, with metformin users having significantly higher pCR
      rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P =
      0.007). Metformin use was significantly associated with pCR rate on univariate (P
      = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking
      metformin had significantly increased disease-free (P = 0.013) and overall
      survival (P = 0.008) compared with other diabetic patients. Metformin use is
      associated with significantly higher pCR rates as well as improved survival.
      These promising data warrant further prospective study.

PMID- 24133634
TI  - Coco expression in lung promotes organ-specific metastasis.

PMID- 24133635
TI  - A new species of long-necked turtle (Pleurodira: Chelidae: Chelodina) from the
      late Miocene Alcoota Local Fauna, Northern Territory, Australia.
AB  - The new species Chelodina (Chelodina) murrayi is described from the late Miocene
      Alcoota Local Fauna of central Australia, in the Northern Territory. The new
      species is based on shell fragments and can be diagnosed by a ventrally reflexed
      anterior margin of the plastron, a ventrally narrowed cervical scute and strongly
      dorsally curved margins of the carapace extending from approximately peripheral
      two to peripheral nine or ten as well as by a unique combination of characters.
      Within Chelodina the new species is part of the nominal subgenus and within that
      subgenus it is most closely related to the Chelodina (Chelodina) novaeguineae
      species group. This is not only the oldest record but also the most southerly
      occurrence of this species group. 

PMID- 24133637
TI  - Decadal changes and delayed avian species losses due to deforestation in the
      northern Neotropics.
AB  - How avifauna respond to the long-term loss and fragmentation of tropical forests
      is a critical issue in biodiversity management. We use data from over 30 years to
      gain insights into such changes in the northernmost Neotropical rainforest in the
      Sierra de Los Tuxtlas of southern Veracruz, Mexico. This region has been
      extensively deforested over the past half-century. The Estacion de Biologia
      Tropical Los Tuxtlas, of the Universidad Nacional Autonoma de Mexico (UNAM),
      protects a 640 ha tract of lowland forest. It became relatively isolated from
      other forested tracts between 1975 and 1985, but it retains a corridor of forest
      to more extensive forests at higher elevations on Volcan San Martin. Most
      deforestation in this area occurred during the 1970s and early 1980s. Forest
      birds were sampled on the station and surrounding areas using mist nets during
      eight non-breeding seasons from 1973 to 2004 (though in some seasons netting
      extended into the local breeding season for some species). Our data suggested
      extirpations or declines in 12 species of birds subject to capture in mist nets.
      Six of the eight species no longer present were captured in 1992-95, but not in
      2003-2004. Presence/absence data from netting and observational data suggested
      that another four low-density species also disappeared since sampling began. This
      indicates a substantial time lag between the loss of habitat and the apparent
      extirpation of these species. Delayed species loss and the heterogeneous nature
      of the species affected will be important factors in tropical forest management
      and conservation. 

PMID- 24133636
TI  - Antimicrobial resistance and molecular epidemiology of Staphylococcus aureus from
      Ulaanbaatar, Mongolia.
AB  - This study aimed to characterize Staphylococcus aureus (S. aureus) strains
      isolated from human infections in Mongolia. Infection samples were collected at
      two time periods (2007-08 and 2011) by the National Center for Communicable
      Diseases (NCCD) in Ulaanbaatar, Mongolia. S. aureus isolates were characterized
      using polymerase chain reaction (PCR) for mecA, PVL, and sasX genes and tested
      for agr functionality. All isolates were also spa typed. A subset of isolates
      selected by frequency of spa types was subjected to antimicrobial susceptibility
      testing and multilocus sequence typing. Among 251 S. aureus isolates, genotyping
      demonstrated methicillin resistance in 8.8% of isolates (22/251). Approximately
      28% of the tested S. aureus isolates were observed to be multidrug resistant
      (MDR). Sequence type (ST) 154 (spa t667) was observed to be a strain with high
      virulence potential, as all isolates for this spa type were positive for PVL, had
      a functional agr system and 78% were MDR. S. aureus isolates of ST239 (spa t037)
      were observed to cause infections and roughly 60% had functional agr system with
      a greater proportion being MDR. Additionally, new multilocus sequence types and
      new spa types were identified, warranting continued surveillance for S. aureus in
      this region. 

PMID- 24133638
TI  - SUMOylation in Trypanosoma brucei.
AB  - Small ubiquitin like modifier (SUMO) proteins are involved in many processes in
      eukaryotes. We here show that Trypanosoma brucei SUMO (Tb927.5.3210) modifies
      many proteins. The levels of SUMOylation were unaffected by temperature changes
      but were increased by severe oxidative stress. We obtained evidence that
      trypanosome homologues of the SUMO conjugating enzyme Ubc9 (Tb927.2.2460) and the
      SUMO-specific protease SENP (Tb927.9.2220) are involved in SUMOylation and SUMO
      removal, respectively. 

PMID- 24133639
TI  - Assessment of heavy metal (Cu, Ni, Fe, Co, Mn, Cr, Zn) pollution in effluent
      dominated rivulet water and their effect on glycogen metabolism and histology of
      Mastacembelus armatus.
AB  - The present study was conducted to examine the contamination of rivulet situated
      at Kasimpur, Aligarh (27.218 degrees  N; 79.378 degrees  E). It receives the
      wastewater of Harduaganj Thermal Power Plant (HTPS) containing fly ash and heavy
      metals. Among the heavy metals estimated in the rivulet water, Fe (8.71 mgL(-1))
      was present in the highest concentration followed by Cu (0.86 mgL(-1)), Zn (0.30
      mgL(-1)) Mn (0.21 mgL(-1)), Ni (0.12 mgL(-1)), Co (0.11 mgL(-1)) and Cr (0.10
      mgL(-1)). The values for the heavy metals such as Fe, Ni and Mn were beyond the
      limits set by UNEPGEMS. Bioaccumulation of these heavy metals was detected in
      tissues such as gills, liver, kidney, muscle and integument of the fish
      Mastacembelus armatus. Accumulation of Fe (213.29 - 2601.49 mgkg(-1).dw) was
      highest in all the organs. Liver was the most influenced organ and integument had
      the least metal load. The accumulation of Fe, Zn, Cu and Mn, observed in the
      tissues were above the values recommended by FAO/WHO. Biochemical estimation
      related to blood glucose, liver and muscle glycogen conducted showed significant
      (p < 0.01) elevation in blood glucose content over control (17.73%), whereas
      liver glycogen dropped significantly (p < 0.01) over control (-89.83%), and
      similarly muscle glycogen also decreased significantly (p < 0.05) over control (
      71.95%), suggesting enhanced glycolytic capacity to fuel hepatic metabolism.
      Histopathological alterations were also observed in selected organs (gills, liver
      and kidney) of Mastacembelus armatus. 

PMID- 24133640
TI  - Genomic and expression analysis of a solute carrier protein (CcSLC25a5) gene from
      Cyprinus carpio Linnaeus.
AB  - Using the Genefishing method, we identified seven potential regulatory genes
      involved in the process of scale morphogenesis in fishes. We further
      characterized a novel solute carrier protein gene (CcSLC), from the common carp
      which is differentially expressed in mirror carp and Jianli. The ORF encodes a
      peptide of 298 amino acids with a molecular mass of 31.5 kDa and a theoretical
      isoelectric point of 7.49. ScanProsite analysis indicated that it is a putative
      solute carrier protein that contains a substrate binding site. CcSLC was detected
      in carp embryos by in situ hybridization in the 70%-epiboly, 6-somite, and 14
      somite embryonic stages. Gene expression stopped at the long pec stage. However,
      CcSLC25a5 was re-expressed during the initiation of scale formation in the
      regions that were scale covered. These findings provide novel insights into the
      features of early carp embryo and scale development. 

PMID- 24133641
TI  - Clinicopathological characteristic and clinical handling of the patients with 2
      cm or less gastric GISTs.
AB  - BACKGROUND: We previously reported that safety and efficacy of mucosal cutting
      biopsy for diagnosing included 2 cm or less gastric GISTs. However, there have
      been no reports stating the clinicopathological characteristic and clinical
      handling of the patients with 2 cm or less gastric GISTs. The aim of our study is
      to investigate the clinicopathological characteristic and clinical handling of
      the patients with 2 cm or less gastric GISTs. METHODS: The 19 patients diagnosed
      with GIST by mucosal cutting biopsy were divided into 2 groups: Group I; subjects
      were GISTs with 2 cm or less, Group II; subjects were GISTs >2 cm. We compared
      the 2 groups in terms of mean age, tumor size, tumor site, histopathological risk
      grade. In cases that underwent surgery with a diagnosis of GIST, we compared the
      pre- and postoperative histopathological diagnosis, and the histopathlogical risk
      grade within each group. RESULTS: The mean age and tumor size were significantly
      higher in Group I than in Group II. Meanwhile, there were no significant
      differences between the 2 groups, sex ratio, tumor site. All lesions were at
      histopathological risk grade at very low risk and low risk respectively. In 17
      patients with GIST who underwent surgery, the histopathological diagnoses,
      immunostaining were in agreement with those from the mucosal cutting biopsy
      specimens in all cases, but mitotic count of one patient was not in agreement in
      group II. CONCLUSIONS: The 2 cm or less gastric GISTs diagnosed with
      histpathlogical very low risk can be considered acceptable to follow-up.

PMID- 24133642
TI  - Isolation of RNA from equine peripheral blood cells: comparison of methods.
AB  - Gene expression studies in equine research involve the use of whole blood samples
      as a vital source of RNA. To determine the optimal method for RNA isolation from
      equine whole blood, we compared three RNA isolation strategies using different
      commercially available kits to evaluate the yield and quality of equine RNA. All
      3 methods produced RNA with high quality. Though it did not produce the highest
      yield, combining the quality, yield and the need for the downstream application
      in our project, LeukoLOCKTM total RNA isolation system was the best RNA
      extraction method. 

PMID- 24133644
TI  - Identification of harmful cyanobacteria in the Sacramento-San Joaquin Delta and
      Clear Lake, California by DNA barcoding.
AB  - Accurate identification of cyanobacteria using traditional morphological taxonomy
      is challenging due to the magnitude of phenotypic plasticity among natural algal
      assemblages. In this study, molecular approach was utilized to facilitate the
      accurate identification of cyanobacteria in the Sacramento-San Joaquin Delta and
      in Clear Lake in Northern California where recurring blooms have been observed
      over the past decades. Algal samples were collected from both water bodies in
      2011 and the samples containing diverse cyanobacteria as identified by
      morphological taxonomy were chosen for the molecular analysis. The 16S ribosomal
      RNA genes (16S rDNA) and the adjacent internal transcribed spacer (ITS) regions
      were amplified by PCR from the mixed algal samples using cyanobacteria generic
      primers. The obtained sequences were analyzed by similarity search (BLASTN) and
      phylogenetic analysis (16S rDNA) to differentiate species sharing significantly
      similar sequences. A total of 185 plasmid clones were obtained of which 77 were
      successfully identified to the species level: Aphanizomenon flos-aquae,
      Dolichospermum lemmermannii (taxonomic synonym: Anabaena lemmermannii),
      Limnoraphis robusta (taxonomic synonym: Lyngbya hieronymusii f. robusta) and
      Microcystis aeruginosa. To date, Dolichospermum and Limnoraphis found in Clear
      Lake have only been identified to the genus lavel by microscopy. During the
      course of this study, morphological identification and DNA barcoding confirmed A.
      flos-aquae as the predominant cyanobacterium in the Sacramento-San Joaquin Delta
      indicating a shift from M. aeruginosa that have dominated the blooms in the past
      decade. Lastly, the species-specific identification of Limnoraphis robusta in
      Clear Lake is another significant finding as this cyanobacterium has, thus far,
      only been reported in Lake Atitlan blooms in Guatemala. 

PMID- 24133643
TI  - Muscle free amino acid profiles are related to differences in skeletal muscle
      growth between single and twin ovine fetuses near term.
AB  - Twin sheep fetuses have reduced skeletal muscle weight near birth relative to
      singles as a result of restricted muscle hypertrophy. Intracellular free amino
      acids (FAA) are reported to regulate metabolic pathways which control muscle
      protein accretion, whereby reduced intracellular content of specific FAA may
      reduce their activation and therefore, muscle hypertrophy. The aim of this study
      was to determine whether differences in muscle weight between singleton and twin
      fetuses, under different maternal conditions is associated with reduced
      concentration of specific FAA. The FAA content in the semitendinosus muscle (ST)
      in singleton and twin fetuses (rank) at 140 days of gestation from heavy (H) or
      light (L) ewes fed ad libitum (A) or maintenance (M) level of nutrition was
      measured. Muscle weight was reduced in twin fetuses compared to singletons in all
      groups. Reduced concentrations of leucine, threonine and valine, but higher
      concentrations of methionine, ornithine, lysine and serine were found in twin
      fetuses compared to singletons. Maternal size and nutrition interaction with rank
      resulted in reduced glutamine in twins from HM-ewes (H-ewes under M nutrition)
      compared to their singleton counterparts. Maternal weight interaction with
      pregnancy rank reduced the concentration of arginine in twins, with a larger
      effect on H-ewes compared with L-ewes. Maternal size interaction with pregnancy
      rank resulted in twins from M-ewes to have lower alanine, while twins from A-ewes
      had lower aspartic acid concentration compared to singletons. The ST muscle
      weight was positively correlated only with arginine concentration after taking
      into account rank, size and nutrition. The present results indicate that reduced
      concentrations of specific intracellular FAA, such as arginine, leucine, valine,
      glutamine, which are known to play a role in muscle growth, could be acting as
      limiting factors for muscle hypertrophy in twin fetuses during late gestation.
      Ewe size and nutrition can influence the concentration of specific FAA in muscle
      and should be considered in any intervention plan to improve twin fetal muscle
      growth. 

PMID- 24133645
TI  - An oxidoreductase from 'Alphonso' mango catalyzing biosynthesis of furaneol and
      reduction of reactive carbonyls.
AB  - Two furanones, furaneol (4-hydroxy-2,5-dimethyl-3(2H)-furanone) and mesifuran
      (2,5-dimethyl-4-methoxy-3(2H)-furanone), are important constituents of flavor of
      the Alphonso cultivar of mango (Mangifera indica). To get insights into the
      biosynthesis of these furanones, we isolated an enone oxidoreductase gene from
      the Alphonso mango. It has high sequence similarity to an alkenal/one
      oxidoreductase from cucumber (79% identity) and enone oxidoreductases from tomato
      (73% identity) and strawberry (72% identity). The complete open reading frame was
      expressed in E. coli and the (his)6-tagged recombinant protein was purified by
      affinity chromatography. The purified protein assayed with NADH as a reducing
      agent converted D-fructose-1,6-diphosphate into furaneol, the immediate precursor
      of mesifuran. The enzyme was also able to convert two highly reactive carbonyls,
      3-buten-2-one and 1-penten-3-one, produced by lipid peroxidation in plants, into
      their saturated derivatives. Expression profiling in various ripening stages of
      Alphonso fruits depicted an expression maxima at 10 days after harvest stage,
      shortly before the appearance of the maximum amount of furanones (completely ripe
      stage, 15 days after harvest). Although no furanones were detected at the 0 day
      after harvest stage, significant expression of this gene was detected in the
      fruits at this stage. Overall, the results suggest that this oxidoreductase plays
      important roles in Alphonso mango fruits. 

PMID- 24133646
TI  - A statistical approach to quantitative data validation focused on the assessment
      of students' perceptions about biotechnology.
AB  - Student awareness levels are frequently used to evaluate the effectiveness of
      educational policies to promote scientific literacy. Over the last years several
      studies have been developed to assess students' perceptions towards science and
      technology, which usually rely on quantitative methods to achieve broad
      characterizations, and obtain quantifiable and comparable data. Although the
      usefulness of this information depends on its validity and reliability,
      validation is frequently neglected by researchers with limited background in
      statistics. In this context, we propose a guideline to implement a statistical
      approach to questionnaire validation, combining exploratory factor analysis and
      reliability analysis. The work focuses on the psychometric analysis of data
      provided by a questionnaire assessing 1196 elementary and high school students'
      perceptions about biotechnology. Procedural guidelines to enhance the efficiency
      of quantitative inquiry surveys are given, by discussing essential methodological
      aspects and relevant criteria to integrate theory into practice. 

PMID- 24133647
TI  - Effect of copper sulfate on the survival and growth performance of Caspian Sea
      kutum, Rutilus frisii kutum.
AB  - The aim of present study was to determine the LC50/96 h value of copper sulfate
      and determine the growth performance of Caspian Sea kutum) Rutilus frisii kutum
      (fingerlings during 60-days sub-lethal copper (Cu). After acclimation period to
      two weeks, for determine the LC50/96 h value, total of 27 aquarium with a
      capacity of 60 L each stocked with 10 fishes an aquarium. Tunney four aquarium
      and 8 concentrations of (Cu) composed the 24 treatments while 3 other aquaria
      were used as control. For each treatment, three replications were conducted. And
      experiment to determine the growth performance fish were transferred into
      fiberglass aquaria of 200 L water capacity for growth trials. The treated fish
      were kept in the aquarium containing sub-lethal concentrations of Cu (0.11 and
      0.23 mg L(-1)) and affected to grow for 60 days, while control fish were placed
      in metal free water. The results indicated that median lethal concentrations
      (LC50) of copper to Caspian Sea kutum for 96 h exposure was 2.310 ppm. The
      chronic sub-lethal water-borne Cu exposure to the fish exerted that fish had
      significantly decreased final body weight in comparison to control group. The
      copper sulfate also had significant negative effects on specific growth rate
      (SGR) and feed conversion efficiency (FCE) in comparison to those fed the control
      group. The feed conversion ratio (FCR) and condition factor (CF) were
      significantly increased in comparison with the control group (P < 0.05). Also
      survival rate in experimental treatments in comparison with control group, was
      significantly decreased (P < 0.05). The treated fish exhibited significantly
      lower body weight and length gains than that of control. The increments of fish
      weights, fork and total lengths, condition factor, feed intake and condition
      factor of treated and control fish varied significantly during study period.
      Hence, concluded that copper sulfate is toxic for Caspian sea kutum (Rutilus
      frisii kutum). 

PMID- 24133648
TI  - Trace elements can influence the physical properties of tooth enamel.
AB  - In previous studies, we showed that the size of apatite nanocrystals in tooth
      enamel can influence its physical properties. This important discovery raised a
      new question; which factors are regulating the size of these nanocrystals? Trace
      elements can affect crystallographic properties of synthetic apatite, therefore
      this study was designed to investigate how trace elements influence enamel's
      crystallographic properties and ultimately its physical properties. The
      concentration of trace elements in tooth enamel was determined for 38 extracted
      human teeth using inductively coupled plasma-optical emission spectroscopy (ICP
      OES). The following trace elements were detected: Al, K, Mg, S, Na, Zn, Si, B,
      Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se and Ti. Simple and stepwise multiple
      regression was used to identify the correlations between trace elements
      concentration in enamel and its crystallographic structure, hardness, resistance
      to crack propagation, shade lightness and carbonate content. The presence of some
      trace elements in enamel was correlated with the size (Pb, Ti, Mn) and lattice
      parameters (Se, Cr, Ni) of apatite nanocrystals. Some trace elements such as Ti
      was significantly correlated with tooth crystallographic structure and
      consequently with hardness and shade lightness. We conclude that the presence of
      trace elements in enamel could influence its physical properties. 

PMID- 24133649
TI  - SCLpredT: Ab initio and homology-based prediction of subcellular localization by
      N-to-1 neural networks.
AB  - The prediction of protein subcellular localization is a important step towards
      the prediction of protein function, and considerable effort has gone over the
      last decade into the development of computational predictors of protein
      localization. In this article we design a new predictor of protein subcellular
      localization, based on a Machine Learning model (N-to-1 Neural Networks) which we
      have recently developed. This system, in three versions specialised,
      respectively, on Plants, Fungi and Animals, has a rich output which incorporates
      the class "organelle" alongside cytoplasm, nucleus, mitochondria and
      extracellular, and, additionally, chloroplast in the case of Plants. We
      investigate the information gain of introducing additional inputs, including
      predicted secondary structure, and localization information from homologous
      sequences. To accommodate the latter we design a new algorithm which we present
      here for the first time. While we do not observe any improvement when including
      predicted secondary structure, we measure significant overall gains when adding
      homology information. The final predictor including homology information
      correctly predicts 74%, 79% and 60% of all proteins in the case of Fungi, Animals
      and Plants, respectively, and outperforms our previous, state-of-the-art
      predictor SCLpred, and the popular predictor BaCelLo. We also observe that the
      contribution of homology information becomes dominant over sequence information
      for sequence identity values exceeding 50% for Animals and Fungi, and 60% for
      Plants, confirming that subcellular localization is less conserved than
      structure. SCLpredT is publicly available at http://distillf.ucd.ie/sclpredt/.
      Sequence- or template-based predictions can be obtained, and up to 32kbytes of
      input can be processed in a single submission. 

PMID- 24133650
TI  - Optimization and partial characterization of culture conditions for the
      production of alkaline protease from Bacillus licheniformis P003.
AB  - Proteolytic enzymes have occupied a pivotal position for their practical
      applications. The present study was carried out under shake flask conditions for
      the production of alkaline protease from Bacillus licheniformis P003 in basal
      medium containing glucose, peptone, K2HPO4, MgSO4 and Na2CO3 at pH 10. The effect
      of culture conditions and medium components for maximum production of alkaline
      protease was investigated using one factor constant at a time method along with
      its characterization. Maximum level of enzyme production was obtained after 48h
      of incubation with 2% inoculum size at 42 degrees C, under continuous agitation
      at 150 rpm, in growth medium of pH 9. Highest enzyme production was obtained
      using 1% rice flour as carbon source and 0.8% beef extract as organic nitrogen
      source. Results indicated that single organic nitrogen source alone was more
      suitable than using in combinations and there was no significant positive effect
      of adding inorganic nitrogen sources in basal medium. After optimization of the
      parameters, enzyme production was increased about 20 fold than that of in basal
      medium. The crude enzyme was highly active at pH 10 and stable from pH 7-11. The
      enzyme showed highest activity (100%) at 50 degrees C, and retained 78% relative
      activity at 70 degrees C. Stability studies showed that the enzyme retained 75%
      of its initial activity after heating at 60 degrees C for 1h. The enzyme retained
      about 66% and 46% of its initial activity after 28 days of storage at 4 degrees C
      and room temperature (25 degrees C) respectively. Mn(2+) and Mg(2+) increased the
      residual activity of the enzyme, whereas Fe(2+) moderately inhibited its residual
      activity. When pre-incubated with Tween-20, Tween-80, SDS and H2O2, each at 0.5%
      concentration, the enzyme showed increased residual activity. These
      characteristics may make the enzyme suitable for several industrial applications,
      especially in leather industries. 

PMID- 24133651
TI  - Effect of the amino chain length and the transformation into citric acid salts of
      aryl-diphenyl-butenes and ferrocenyl-diphenyl-butenes bearing two
      dimethylaminoalkyl chains on their antimicrobial activities.
AB  - In a previous work we have demonstrated the antimicrobial activity of ferrocenyl
      or phenyl derivatives of diphenyl butene series. This finding has opened a new
      area of applications of organometallic compounds. In order to improve these
      activities, we have synthesized new organic and organometallic diaryl butene
      compounds with different lengths of their amino chains. These new compounds, and
      also their ammonium salts, were tested against man pathogenic microorganisms
      Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442),
      Staphylococcus aureus (ATCC 6538) and Enterococcus hirae (ATCC 10541). It emerged
      from the tests that the Gram+ bacteria are more sensitive to the compounds than
      Gram-, and the compounds with 3 carbon amino chains have a better antimicrobial
      activity than the one having a chain of 2 or 4 carbons. The transformation of
      compounds to citrate salts was accompanied by a significant regression of
      antibacterial activity against Pseudomonas aeruginosa, for both organic and
      ferrocenic molecules. This resistance problem has been solved using
      hydrochlorides salts rather than citrates one. 

PMID- 24133652
TI  - Cluster headache associated with acute maxillary sinusitis.
AB  - BACKGROUND: Cluster headache is a primary headache by definition not caused by
      any known underlying structural pathology. However, symptomatic cases have been
      described, for example tumours, particularly pituitary adenomas, malformations,
      and infections/inflammations. The evaluation of cluster headache is an issue
      unresolved. CASE DESCRIPTION: I present a case of a 24-year-old patient who
      presented with a 4-week history of side-locked attacks of pain located in the
      left orbit. He satisfied the revised International Classification of Headache
      Disorders criteria for cluster headache. His medical and family histories were
      unremarkable. There was no history of headache. A diagnosis of cluster headache
      was made. The patient responded to symptomatic treatment. Low-dose computer
      tomography scan after 2 weeks displayed a left-sided acute maxillary sinusitis.
      The headache attacks resolved completely after treatment with antibiotics and
      sinus puncture. DISCUSSION AND EVALUATION: Although I cannot exclude an
      unintentional comorbidity, in my opinion, the co-occurrence of an acute maxillary
      sinusitis with unilateral headache, in a hitherto headache-free man, points
      toward the fact that in this case the cluster headache was caused or triggered by
      the sinusitis. The headache attacks resolved completely after the treatment and
      the patient also remained headache free at the follow-up. The response of the
      headache to sumatriptan and other typical cluster headache medications does not
      exclude a secondary form. Symptomatic cluster headaches responsive to this
      therapy have been described. Associated cranial lesions such as infections have
      been reported in cluster headache patients and the attacks may be clinically
      indistinguishable from the primary form. CONCLUSIONS: Neuroimaging, preferably
      contrast-enhanced magnetic resonance imaging including sinuses should always be
      considered in patients with cluster headache despite normal neurological
      examination. Acute maxillary sinusitis can present as cluster headache.

PMID- 24133653
TI  - Synthesis and characterization of transition metal complexes of 4-Amino-5-pyridyl
      4H-1,2,4-triazole-3-thiol.
AB  - Series of coordination complexes of Ni(II), Cu(II), Zn(II), Cd(II) and Sn(II)
      metal with 4-amino-5-(pyridyl)-4H-1,2,4-triazole-3-thiol, as a ligand has been
      successfully prepared in alcoholic medium. The prepared complexes were
      characterized quantitatively and qualitatively by using: microelemental analysis,
      FTIR spectroscopy, UV-visible spectroscopy, (1)H and (13)C NMR, magnetic
      susceptibility and conductivity measurements. This triazole ligand act as
      bidentate that coordination to the metal ions through sulphur and amine group.
      According to the spectral data of the complexes a tetrahedral geometry was
      suggested for these complexes except Cu (II) complexes which exhibit a square
      structure. 

PMID- 24133655
TI  - Direct measurements of human colon crypt stem cell niche genetic fidelity: the
      role of chance in non-darwinian mutation selection.
AB  - Perfect human stem cell genetic fidelity would prevent aging and cancer. However,
      perfection would be difficult to achieve, and aging is universal and cancers
      common. A hypothesis is that because mutations are inevitable over a human
      lifetime, downstream mechanisms have evolved to manage the deleterious effects of
      beneficial and lethal mutations. In the colon, a crypt stem cell architecture
      reduces the number of mitotic cells at risk for mutation accumulation, and
      multiple niche stem cells ensure that a lethal mutation within any single stem
      cell does not lead to crypt death. In addition, the architecture of the colon
      crypt stem cell niche may harness probability or chance to randomly discard many
      beneficial mutations that might lead to cancer. An analysis of somatic chromosome
      copy number alterations (CNAs) reveals a lack of perfect fidelity in individual
      normal human crypts, with age-related increases and higher frequencies in
      ulcerative colitis, a proliferative, inflammatory disease. The age-related
      increase in somatic CNAs appears consistent with relatively normal replication
      error and cell division rates. Surprisingly, and similar to point mutations in
      cancer genomes, the types of crypt mutations were more consistent with random
      fixation rather than selection. In theory, a simple "non-Darwinian" way to
      nullify selection is to reduce the size of the reproducing population. Fates are
      more determined by chance rather than selection in very small populations, and
      therefore selection may be minimized within small crypt niches. The desired
      effect is that many beneficial mutations that might lead to cancer are randomly
      lost by drift rather than fixed by selection. The subdivision of the colon into
      multiple very small stem cell niches may trade Darwinian evolution for non
      Darwinian somatic cell evolution, capitulating to aging but reducing cancer
      risks. 

PMID- 24133654
TI  - HERV-K and LINE-1 DNA Methylation and Reexpression in Urothelial Carcinoma.
AB  - Changes in DNA methylation frequently accompany cancer development. One prominent
      change is an apparently genome-wide decrease in methylcytosine that is often
      ascribed to DNA hypomethylation at retroelements comprising nearly half the
      genome. DNA hypomethylation may allow reactivation of retroelements, enabling
      retrotransposition, and causing gene expression disturbances favoring tumor
      development. However, neither the extent of hypomethylation nor of retroelement
      reactivation are precisely known. We therefore assessed DNA methylation and
      expression of three major classes of retroelements (LINE-1, HERV-K, and AluY) in
      human urinary bladder cancer tissues and cell lines by pyrosequencing and
      quantitative reverse transcription-polymerase chain reaction, respectively. We
      found substantial global LINE-1 DNA hypomethylation in bladder cancer going along
      with a shift toward full-length LINE-1 expression. Thus, pronounced differences
      in LINE-1 expression were observed, which may be promoted, among others, by LINE
      1 hypomethylation. Significant DNA hypomethylation was found at the HERV
      K_22q11.23 proviral long terminal repeat (LTR) in bladder cancer tissues but
      without reactivation of its expression. DNA methylation of HERVK17, essentially
      absent from normal urothelial cells, was elevated in cell lines from invasive
      bladder cancers. Accordingly, the faint expression of HERVK17 in normal
      urothelial cells disappeared in such cancer cell lines. Of 16 additional HERV-Ks,
      expression of 7 could be detected in the bladder, albeit generally at low levels.
      Unlike in prostate cancers, none of these showed significant expression changes
      in bladder cancer. In contrast, expression of the AluYb8 but not of the AluYa5
      family was significantly increased in bladder cancer tissues. Collectively, our
      findings demonstrate a remarkable specificity of changes in expression and DNA
      methylation of retroelements in bladder cancer with a significantly different
      pattern from that in prostate cancer. 

PMID- 24133657
TI  - Targeting nutrient retrieval by Francisella tularensis.

PMID- 24133656
TI  - Characterization of a novel zinc transporter ZnuA acquired by Vibrio
      parahaemolyticus through horizontal gene transfer.
AB  - Vibrio parahaemolyticus is a clinically important foodborne pathogen that causes
      acute gastroenteritis worldwide. It has been shown that horizontal gene transfer
      (HGT) contributes significantly to virulence development of V. parahaemolyticus.
      In this study, we identified a novel znuA homolog (vpa1307) that belongs to a
      novel subfamily of ZnuA, a bacterial zinc transporter. The vpa1307 gene is
      located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in
      both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic
      analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus
      clinical isolates possessing this gene. The expression of vpa1307 gene in V.
      parahaemolyticus clinical strain VP3218 is induced under zinc limitation
      condition. Gene deletion and complementation assays confirmed that vpa1307
      contributes to the growth of VP3218 under zinc depletion condition and that
      conserved histidine residues of Vpa1307 contribute to its activity. Importantly,
      vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain
      degree of virulence in murine model. These results suggest that the horizontally
      acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence
      of Vibrio species. 

PMID- 24133658
TI  - Fungal zinc metabolism and its connections to virulence.
AB  - Zinc is a ubiquitous metal in all life forms, as it is a structural component of
      the almost 10% of eukaryotic proteins, which are called zinc-binding proteins. In
      zinc-limiting conditions such as those found during infection, pathogenic fungi
      activate the expression of several systems to enhance the uptake of zinc. These
      systems include ZIP transporters (solute carrier 39 family) and secreted
      zincophores, which are proteins that are able to chelate zinc. The expression of
      some fungal zinc uptake systems are regulated by a master regulator (Zap1), first
      characterized in the yeast Saccharomyces cerevisiae. In this review, we highlight
      features of zinc uptake and metabolism in human fungal pathogens and aspects of
      the relationship between proper zinc metabolism and the expression of virulence
      factors and adaptation to the host habitat. 

PMID- 24133659
TI  - Options for the management of antiviral resistance during hepatitis B therapy:
      reflections on battles over a decade.
AB  - Although much advancement has been achieved in the treatment of chronic hepatitis
      B, antiviral resistance is still a challenging issue. Previous generation
      antiviral agents have already developed resistance in a number of patients, and
      it is still being used especially in resource limited countries. Once antiviral
      resistance occurs, it predisposes to subsequent resistance, resulting in
      multidrug resistance. Therefore, prevention of initial antiviral resistance is
      the most important strategy, and appropriate choice and modification of therapy
      would be the cornerstone in avoiding treatment failures. Until now, management of
      antiviral resistance has been evolving from sequential therapy to combination
      therapy. In the era of tenofovir, the paradigm shifts again, and we have to
      decide when to switch and when to combine on the basis of newly emerging clinical
      data. We expect future eradication of chronic hepatitis B virus infection by
      proper prevention and optimal management of antiviral resistance. 

PMID- 24133660
TI  - Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.
AB  - Liver plays a central role in the biogenesis of major metabolites including
      glucose, fatty acids, and cholesterol. Increased incidence of obesity in the
      modern society promotes insulin resistance in the peripheral tissues in humans,
      and could cause severe metabolic disorders by inducing accumulation of lipid in
      the liver, resulting in the progression of non-alcoholic fatty liver disease
      (NAFLD). NAFLD, which is characterized by increased fat depots in the liver,
      could precede more severe diseases such as non-alcoholic steatohepatitis (NASH),
      cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in
      the liver can be traced by increased uptake of free fatty acids into the liver,
      impaired fatty acid beta oxidation, or the increased incidence of de novo
      lipogenesis. In this review, I would like to focus on the roles of individual
      pathways that contribute to the hepatic steatosis as a precursor for the NAFLD. 

PMID- 24133662
TI  - Chasing after novel non-invasive markers to identify advanced fibrosis in NAFLD.

PMID- 24133663
TI  - Elevated red cell distribution width is associated with advanced fibrosis in
      NAFLD.
AB  - BACKGROUND/AIMS: The red-blood-cell distribution width (RDW) is a newly
      recognized risk marker in patients with cardiovascular disease, but its role in
      nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of
      the present study was to determine the association between RDW values and the
      level of fibrosis in NAFLD according to BARD and FIB-4 scores. METHODS: This
      study included 24,547 subjects who had been diagnosed with NAFLD based on
      abdominal ultrasonography and questionnaires about alcohol consumption. The
      degree of liver fibrosis was determined according to BARD and FIB-4 scores. The
      association between RDW values and the degree of fibrosis in NAFLD was analyzed
      retrospectively. RESULTS: After adjusting for age, hemoglobin level, mean
      corpuscular volume, history of hypertension, history of diabetes, and high
      sensitivity C-reactive protein, the RDW values were 12.61+/-0.41% (mean+/-SD),
      12.70+/-0.70%, 12.77+/-0.62%, 12.87+/-0.82%, and 13.25+/-0.90% for those with
      BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71+/-0.72%, 12.79+/-0.66%,
      and 13.23+/-1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and >=2.67,
      respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and
      FIB-4 score of >=1.3) increased with the RDW [BARD score: 51.1% in quartile 1
      (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After
      adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared
      to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69
      (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score. CONCLUSIONS: Elevated RDW is
      independently associated with advanced fibrosis in NAFLD.

PMID- 24133664
TI  - Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi
      do, Korea.
AB  - BACKGROUND/AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) in
      Korea has increased recently. The aim of the present study was to determine the
      regional differences in the prevalence and characteristics of NAFLD. METHODS:
      From January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents
      receiving a health examination at our institution were enrolled in this cross
      sectional study. After applying exclusion criteria, the data of 141,610 subjects
      (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was
      established by ultrasound examination. RESULTS: The overall prevalence of NAFLD
      was 27.3% (38.3% in men, 12.6% in women). When standardized according to age,
      area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized
      prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001).
      The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul
      (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi
      do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in
      Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001). CONCLUSIONS: The regional
      prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are
      needed to establish the etiology of this difference.

PMID- 24133666
TI  - The secondary prophylactic efficacy of beta-blocker after endoscopic gastric
      variceal obturation for first acute episode of gastric variceal bleeding.
AB  - BACKGROUND/AIMS: The most appropriate treatment for acute gastric variceal
      bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using
      Histoacryl(r). However, the secondary prophylactic efficacy of beta-blocker (BB)
      after GVO for the first acute episode of GVB has not yet been established. The
      secondary prophylactic efficacy of BB after GVO for the first acute episode of
      GVB was evaluated in this study. METHODS: Ninety-three patients at Soonchunhyang
      University Hospital with acute GVB who received GVO using Histoacryl(r) were
      enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO
      alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB
      group). This study was intended for patients in whom a desired heart rate was
      reached. The rates of rebleeding-free survival and overall survival were
      calculated for the two study groups using Kaplan-Meyer analysis and Cox's
      proportional-hazards model. RESULTS: The follow-up period after the initial
      eradication of gastric varices was 18.14+/-25.22 months (mean+/-SD). During the
      follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB
      patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16
      (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not
      differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months,
      respectively; P=0.774), whereas the mean overall survival time did differ (52.54
      and 72.65 months, respectively; P=0.036). CONCLUSIONS: Adjuvant BB therapy after
      GVO using Histoacryl(r) for the first acute episode of GVB could decrease the
      mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no
      benefit for the secondary prevention of rebleeding in GV.

PMID- 24133665
TI  - Lamivudine plus adefovir combination therapy for lamivudine resistance in
      hepatitis-B-related hepatocellular carcinoma patients.
AB  - BACKGROUND/AIMS: Lamivudine (LAM) plus adefovir (ADV) combination therapy has
      been accepted as one of the best treatments for LAM-resistant chronic hepatitis B
      (CHB). The aim of this study was to determine the efficacy of this combination
      therapy in hepatocellular carcinoma (HCC) patients. METHODS: The medical records
      of CHB patients who developed LAM resistance and were treated with LAM plus ADV
      combination therapy for more than 6 months were reviewed. Their virological
      response (VR; undetectable HBV DNA) and biochemical response (BR; alanine
      aminotransferase normalization) were evaluated, and the findings of HCC and non
      HCC patients were compared. RESULTS: The data from 104 patients (19 with HCC and
      85 without HCC) were analyzed. The VR rates did not differ significantly between
      the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs.
      67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs.
      71.0% at 48 months (P=1.000). The BR rates also did not differ significantly
      between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24
      months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at
      48 months (P=0.591). CONCLUSIONS: The efficacy of LAM plus ADV combination
      therapy is comparable in HCC and non-HCC patients.

PMID- 24133667
TI  - Efficacy and safety of hepatic arterial infusion chemotherapy for advanced
      hepatocellular carcinoma as first-line therapy.
AB  - BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) with 5
      fluorouracil and cisplatin for intractable advanced hepatocellular carcinoma
      (HCC) may have survival benefits. We aimed to determine the efficacy and safety
      of HAIC for advanced HCC as first-line therapy. METHODS: A total of 54 patients
      who received only HAIC with 5-fluorouracil (750 mg/m(2) on days 1-4) and
      cisplatin (25 mg/m(2) on days 1-4) for advanced HCC from Jan. 2009 to Dec. 2011
      were selected. According to Child-Pugh class, the overall survival (OS),
      progression-free survival (PFS), and adverse events after HAIC were investigated
      retrospectively. RESULTS: Median OS and PFS between the Child-Pugh A group (n=24)
      and the Child-Pugh B/C group (n=30) were 8.7 (95% confidence interval [CI]: 4.7
      12.7) vs. 3.7 months (95% CI: 2.0-5.3), and 7.1 (95% CI: 3.8-10.4) vs. 3.6 months
      (95% CI: 2.0-5.2), respectively. Although median OS and PFS were not
      statistically significant between the two groups (P=0.079, P=0.196), the Child
      Pugh class B/C tended to influence poor OS. Serious adverse events >= grade 3
      occurred frequently in both groups (83.3 vs. 96.7%, P=0.159). Responders (22.2%,
      complete or partial response) significantly differed in median OS, compared to
      non-responders (13.1 vs. 4.4 months, P=0.019). Achievement of complete or partial
      response was an independent prognostic factor of OS (hazard ratio: 0.4, 95% CI:
      0.2-0.8, P=0.011). CONCLUSIONS: Achievement of response after HAIC provide a
      survival benefit in patients with advanced HCC, but HAIC should be administered
      cautiously in patients with Child-Pugh class B/C, because of a relatively low
      survival and high incidence of serious adverse events.

PMID- 24133668
TI  - Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg
      negative hepatitis patients.
AB  - BACKGROUND/AIMS: Relapse has been reported after stopping nucleos(t)ide (NUC)
      therapy in the majority of chronic HBeAg negative hepatitis patients. However,
      the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not
      well known. We investigated the frequency of relapse in HBeAg negative CHB
      patients receiving NUC therapy. METHODS: The NUC therapy was discontinued at
      least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients.
      Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase
      (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal
      range. Virological relapse was defined as HBV DNA >2,000 IU/mL. RESULTS: Clinical
      relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at
      6 months and 12 months off therapy, respectively. Virological relapse developed
      22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The
      factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels,
      treatment duration, and consolidation duration were analyzed to investigate the
      predictive factors associated with 1 year sustained response. Of these factors,
      cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year
      virological relapse rate. Baseline HBV DNA and total treatment duration tended to
      be associated with virological relapse. CONCLUSIONS: Virological relapse
      developed in the majority (73.3%) of HBeAg negative CHB patients and clinical
      relapse developed in the half (53.3%) of patients at 1 year off therapy.
      Cirrhosis may be associated with the low rate of virological relapse.

PMID- 24133661
TI  - KASL clinical practice guidelines: management of alcoholic liver disease.

PMID- 24133669
TI  - Co-development of autoimmune hepatitis and Sjogren's syndrome triggered by the
      administration of herbal medicines.
AB  - Autoimmune hepatitis (AIH) has been reported in association with Sjogren's
      syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co
      development of AIH and SS in a 53-year-old woman after the consumption of herbal
      medicines is described. After admission, the patient complained of dryness in her
      mouth, and she was subsequently diagnosed with SS, which had not been detected
      previously. The patient's bilirubin and aminotransferase levels initially
      decreased following conservative management; however, they later began to
      progressively increase. A diagnosis of AIH was made based on the scoring system
      proposed by the International Autoimmune Hepatitis Group. The patient was
      administered a combination of prednisolone and azathioprine, and the results of
      follow-up liver-function tests were found to be within the normal range. This is
      an unusual case of AIH and SS triggered simultaneously by the administration of
      herbal medicines. 

PMID- 24133670
TI  - Genotype-4 hepatitis E in a human after ingesting roe deer meat in South Korea.
AB  - The recent increase in the number of cases of indigenous hepatitis E virus (HEV)
      infection highlights the importance of identifying the transmission routes for
      the prevention of such infections. Presented herein is the first case of acute
      HEV infection after ingesting wild roe deer meat in South Korea. A 43-year-old
      male presented with abdominal discomfort and jaundice. He had not recently
      traveled abroad, but had eaten raw roe-deer meat 6-8 weeks before the
      presentation. On the 7th day of hospitalization the patient was diagnosed with
      acute viral hepatitis E. Phylogenetic analysis of his serum revealed genotype-4
      HEV. This case supports the possibility of zoonotic transmission of HEV because
      the patient appears to have been infected with genotype-4 HEV after ingesting raw
      deer meat. 

PMID- 24133673
TI  - American Association for Health Education (AAHE) 2011 Membership Survey: Summary
      of Findings.
AB  - The American Association for Health Education (AAHE), a national health education
      organization with the mission of advancing the profession of health education,
      launched the 2011 AAHE membership survey between October 13, 2011 and November 1,
      2011, under the leadership of the AAHE Board of Directors and AAHE Staff. The
      primary objective of the survey was to provide insight into the perspectives of
      AAHE members on several important issues facing the organization including: AAHE
      exiting its parent organization, the American Alliance for Health, Physical
      Education, Recreation and Dance (AAHPERD), and the proposed "modified" merger
      with the Society for Public Health Education (SOPHE), another national health
      education organization. A total of 240 AAHE members completed the survey. A
      majority of respondents were university faculty members in health education, and
      results provide keen insight into AAHE members' perspectives on the AAHE-SOPHE
      modified merger.

PMID- 24133671
TI  - Epithelioid hemangioendothelioma of the liver.

PMID- 24133672
TI  - Primary hepatic lymphoma mimicking acute hepatitis.

PMID- 24133674
TI  - A pyrene-based simple but highly selective fluorescence sensor for Cu(2+) ions
      via a static excimer mechanism.
AB  - A pyrene-based simple fluorosensor has been synthesized by a one step process. It
      exhibited high selectivity towards Cu(2+) ions via fluorescence enhancement of
      monomer and excimer emission. The origin of excimer formation was examined and
      established to be of static in nature from the study of absorption and excitation
      spectra. The observed monomer and excimer emission in the presence and absence of
      Cu(2+) ion with varying pH was studied and provided probable justification. The
      effect of varying portions of water content in solvent on the sensor molecule was
      also examined. The sensor found its proper application in finding accurate and
      trace amount of Cu(2+) ions present in drinking water samples from various
      sources. The detection limit of the current sensor was found to be 4 * 10(-8) M. 

PMID- 24133675
TI  - Nanostructured solid substrates for efficient laser desorption/ionization mass
      spectrometry (LDI-MS) of low molecular weight compounds.
AB  - Analytical applications often require rapid measurement of compounds from complex
      sample mixtures. High-speed mass spectrometry approaches frequently utilize
      techniques based on direct ionization of the sample by laser irradiation, mostly
      by means of matrix-assisted laser desorption/ionization (MALDI). Compounds of low
      molecular weight are difficult to analyze by MALDI, however, because of severe
      interferences in the low m/z range from the organic matrix used for
      desorption/ionization. In recent years, surface-assisted laser
      desorption/ionization (SALDI) techniques have shown promise for small molecule
      analysis, due to the unique properties of nanostructured surfaces, in particular,
      the lack of a chemical background in the low m/z range and enhanced production of
      analyte ions by SALDI. This short review article presents a summary of the most
      promising recent developments in SALDI materials for MS analysis of low molecular
      weight analytes, with emphasis on nanostructured materials based on metals and
      semiconductors. 

PMID- 24133677
TI  - Molecularly imprinted superparamagnetic iron oxide nanoparticles for rapid
      enrichment and separation of cholesterol.
AB  - A general protocol to prepare surface molecularly imprinted polymer core-shell
      superparamagnetic Fe3O4 nanoparticles (Fe3O4@MIP SPNPs), using a surface-mediated
      RAFT polymerization approach, is described. Cholesterol-imprinted Fe3O4@MIP SPNPs
      were obtained by oleic acid-stabilized Fe3O4 nanoparticles with a
      trithiocarbonate agent and subsequently by polymerizing thin molecularly
      imprinted layers composed of dimethylacrylamide and N,N'-methylene(bis)acrylamide
      units. The surface-mediated RAFT polymerization approach allows the synthesis of
      ~20 nm hybrid composite particles with a ~6 nm MIP shell, exhibiting
      superparamagnetic properties (saturation magnetization = 35.4 emu g(-1)) and
      specific molecular recognition of cholesterol. The Fe3O4@MIP SPNPs show the
      capability of rapid enriching and separating cholesterol (~3.1% in weight) and
      are renewable and cyclically exploited due to their monodispersive and
      superparamagnetic features. Moreover, under optimal conditions, the Fe3O4@MIP
      SPNP recoveries of spiked human serum, milk, yolk and beef were 91.6%, 93.6%,
      92.4% and 91.2%, respectively. Finally, the method of molecular imprinting on
      superparamagnetic particles can be extended to a wide range of applications for
      cell sorting, biomolecule enrichment and separation, and drug delivery. 

PMID- 24133678
TI  - High-performance H(2)S detection by redox reactions in semiconducting carbon
      nanotube-based devices.
AB  - Here we report the highly effective detection of hydrogen sulfide (H2S) gas by
      redox reactions based on single-walled carbon nanotubes (SWCNTs) functionalized
      with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as a catalyst and we also
      discuss the important role of water vapor in the electrical conductivity of
      SWCNTs during the sensing of H2S molecules. To explore the H2S sensing mechanism,
      we investigate the adsorption properties of H2S on carbon nanotubes (CNTs) and
      the effects of the TEMPO functionalization using first-principles density
      functional theory (DFT) and we summarize current changes of devices resulting
      from the redox reactions in the presence of H2S. The semiconducting-SWCNT (s
      SWCNT) device functionalized with TEMPO shows a very high sensitivity of 420% at
      60% humidity, which is 17 times higher than a bare s-SWCNT device under dry
      conditions. Our results offer promising prospects for personal safety and real
      time monitoring of H2S gases with the highest sensitivity and low power
      consumption and potentially at a low cost. 

PMID- 24133676
TI  - A visible light photoelectrochemical sensor for tumor marker detection using tin
      dioxide quantum dot-graphene as labels.
AB  - In this paper, a simple and sensitive sandwich-type photoelectrochemical (PEC)
      immunosensor for measurement of biomarkers on a gold nanoparticle-modified indium
      tin oxide (ITO) electrode through electrodeposition for point-of-care testing was
      developed by using a tin dioxide quantum dot-graphene nanocomposite (G-SnO2) as
      an excellent label with amplification techniques. The capture antibody (Ab1) was
      firstly immobilized on the gold nanoparticle-modified ITO electrode due to the
      covalent conjugation, then the antigen and the AuNP/PDDA-G-SnO2 nanocomposite
      nanoparticle labeled signal antibody (Ab2) were conjugated successively to form a
      sandwich-type immunocomplex through a specific interaction. Under irradiation
      with a common ultraviolet lamp (~365 nm, price $50), the SnO2 NPs were excited
      and underwent charge-separation to yield electrons (e(-)) and holes (h(+)). As
      the holes were scavenged by ascorbic acid (AA), the electrons were transferred to
      the ITO electrode through RGO to generate a photocurrent. The photocurrents were
      proportional to the CEA concentrations, and the linear range of the developed
      immunosensor was from 0.005 to 10 ng mL(-1) with a detection limit of 0.036 pg
      mL(-1). The proposed sensor shows high sensitivity, stability, reproducibility,
      and can become a promising platform for other biomolecular detection. 

PMID- 24133681
TI  - Federal Employees Health Benefits Program: members of Congress and Congressional
      staff. Final rule.
AB  - The U.S. Office of Personnel Management (OPM) is issuing a final rule to amend
      the Federal Employees Health Benefits (FEHB) Program regulations regarding
      coverage for Members of Congress and congressional staff.

PMID- 24133682
TI  - About health and disease.

PMID- 24133683
TI  - [Not Available].

PMID- 24133684
TI  - In reply.

PMID- 24133685
TI  - Author's reply: To PMID 23157145.

PMID- 24133686
TI  - In reply.

PMID- 24133687
TI  - [Proceedings of the 13th Symposium: Diabetes mellitus--ocular complications,
      October 12, 2012, Prague, Czech Republic].

PMID- 24133688
TI  - Second annual meeting of the European Society for the study of Human Evolution.

PMID- 24133689
TI  - Human cooperation at the National Evolutionary Synthesis Center.

PMID- 24133690
TI  - Chasing monkeys and finding fossils under the sunsphere.

PMID- 24133691
TI  - The author's reply.

PMID- 24133692
TI  - Medicare program; FY 2014 inpatient prospective payment systems: changes to
      certain cost reporting procedures related to disproportionate share hospital
      uncompensated care payments. Interim final rule with comment period.
AB  - : In the fiscal year (FY) 2014 inpatient prospective payment systems (IPPS)/long
      term care hospital (LTCH) PPS final rule, we established the methodology for
      determining the amount of uncompensated care payments made to hospitals eligible
      for the disproportionate share hospital (DSH) payment adjustment in FY 2014 and a
      process for making interim and final payments. This interim final rule with
      comment period revises certain operational considerations for hospitals with
      Medicare cost reporting periods that span more than one Federal fiscal year and
      also makes changes to the data that will be used in the uncompensated care
      payment calculation in order to ensure that data from Indian Health Service (IHS)
      hospitals are included in Factor 1 and Factor 3 of that calculation.

PMID- 24133694
TI  - Effect of fenspiride on bronchial smooth muscle of rats with chronic obstructive
      pulmonary disease.

PMID- 24133696
TI  - State innovation models: early experiences and challenges of an initiative to
      advance broad health system reform.
AB  - The Centers for Medicare and Medicaid Services and states are partnering to
      transform health care systems by creating and testing new models of care delivery
      and payment. Interviews with officials from states participating in the State
      Innovation Models (SIM) Initiative reveal that the readiness of providers and
      payers to adopt innovations var-ies, requiring different starting points, goals,
      and strategies. So far, effective strategies appear to include: building on past
      reform efforts; redesigning health information technol-ogy to provide reliable,
      targeted data on care costs and quality; and using standard perfor-mance measures
      and financial incentives to spur alignment of providers' and payers' goals. State
      governments also have policy levers to encourage efficient deployment of a
      diverse health care workforce. As federal officials review states' innovation
      plans, set timetables, and provide technical assistance, they can also take steps
      to accommodate the budgetary, political, and time constraints that states are
      facing.

PMID- 24133695
TI  - Non-genomic effects of progesterone on Rho kinase II in rat gastric smooth muscle
      cells.

PMID- 24133693
TI  - Membrane depolarization-induced RhoA/Rho-associated kinase activation and
      sustained contraction of rat caudal arterial smooth muscle involves genistein
      sensitive tyrosine phosphorylation.

PMID- 24133698
TI  - Notice to readers: final 2012 reports of nationally notifiable infectious
      diseases.

PMID- 24133697
TI  - What Americans think of the new insurance marketplaces and Medicaid expansion:
      findings from the Commonwealth Fund Health Insurance Marketplace Survey, 2013.
AB  - The Affordable Care Act's health insurance marketplaces are opening for
      enrollment on October 1, 2013. The Commonwealth Fund Health Insurance Marketplace
      Survey, 2013, finds that only two of five adults are aware of the marketplaces or
      of potential financial help that may be available to them to pay for plans
      purchased though the marketplaces. However, three of five adults who might be
      eligible for these new options said they were likely to take advantage of them.
      The survey also finds broad support for state expansion of the Medicaid program,
      even in states that have not yet decided to expand their programs. While outreach
      and education are critical to ensuring that those eligible for the new coverage
      options will enroll, the survey results suggest that eligible Americans will
      likely take advantage of the law's insurance reforms in the months and years to
      come.

PMID- 24133699
TI  - History lessons.
AB  - There was a time when epidemics were solely the province of infectious diseases.
      Indeed, most dictionary definitions of the term refer first to contagious
      diseases that spread rapidly among a given population.

PMID- 24133700
TI  - Chronic heart failure management in Australia--time for general practice centred
      models of care?

PMID- 24133701
TI  - Reply: To PMID 23781539.

PMID- 24133702
TI  - Interactions between alcohol and prescription medications.

PMID- 24133703
TI  - Reply: To PMID 23781538.

PMID- 24133704
TI  - Hot water immersion for bluebottle stings.

PMID- 24133705
TI  - Underemployment of veterinarians.

PMID- 24133706
TI  - Veterinary applicants.

PMID- 24133707
TI  - The need for greater diversity in our profession.

PMID- 24133708
TI  - Foreign veterinary school accreditation.

PMID- 24133709
TI  - Poetry for new doctors: in memory of Dr Pat Manson.

PMID- 24133710
TI  - Evidence appraisal of Blackham AU, Farrah JP, McCoy TP, Schmidt BS, Shen P.
      Prevention of surgical site infections in high-risk patients with laparotomy
      incisions using negative-pressure therapy. Am J Surg. 2013;205(6):647-654.

PMID- 24133711
TI  - Current world literature. Thyroid.

PMID- 24133712
TI  - Retraction to: "Signaling pathways in tumor vasculogenic mimicry".

PMID- 24133713
TI  - [Determining the dose of azathioprine based on the lower limit of leukocyte count
      in patients with Crohn's disease].

PMID- 24133714
TI  - [Synchronous double primary hepatic cancer: hepatocellular carcinoma and
      intrahepatic cholangiocarcinoma].

PMID- 24133716
TI  - How do vets fare?

PMID- 24133715
TI  - [Is classification of gastric cancer according to distinct therapeutic targets
      applicable in clinical practice?].

PMID- 24133717
TI  - Securing the future of veterinarians.

PMID- 24133718
TI  - Committee'd to excellence.

PMID- 24133719
TI  - How to cope with performance management.

PMID- 24133720
TI  - What we pay for self-education.

PMID- 24133721
TI  - Future directions for animal health in Australia.

PMID- 24133722
TI  - Practice of Excellence award winner.

PMID- 24133723
TI  - Animals and scientific research: the ethics that guide us.

PMID- 24133724
TI  - Re: pricing and charging for veterinary services.

PMID- 24133725
TI  - Breast cryoablation.

PMID- 24133726
TI  - Hospitalist.

PMID- 24133727
TI  - Pediatric critical care medicine.

PMID- 24133728
TI  - Nuclear radiology.

PMID- 24133729
TI  - Sentinel lymph node biopsy for breast cancer.

PMID- 24133730
TI  - Fecal microbiota transplantation for treatment of recurrent C. difficile
      infection.

PMID- 24133732
TI  - Coping with the process of dying and mourning.

PMID- 24133731
TI  - Plagiarism and self-plagiarism.

PMID- 24133733
TI  - Current world literature. Auditory and vestibular science.

PMID- 24133734
TI  - From the Editor: Solving problems.

PMID- 24133735
TI  - 3M ESPE's FiltekTM Supreme Ultra: offering clinicians exceptional strength,
      esthetics, and handling.

PMID- 24133736
TI  - Danville's new ZNano: a state-of-the-art nanofilled universal composite.

PMID- 24133737
TI  - DENTSPLY Caulk's TPH SpectraTM simplifies handling and shade matching.

PMID- 24133738
TI  - Ivoclar Vivadent: a pioneer in dental composite development.

PMID- 24133739
TI  - Septodont's N'Durance dimer flow composite ideal for no-prep abfraction lesion
      treatment.

PMID- 24133740
TI  - Shofu's Beautifil(r) II composite big on therapeutic properties.

PMID- 24133741
TI  - Synca's ENA HRi: delivering optimal, natural-looking esthetics.

PMID- 24133742
TI  - Comment on: Acetabular index values in healthy Turkish children between 6 months
      and 8 years of age: a cross-sectional radiological study.

PMID- 24133743
TI  - Acetabular index values in healthy Turkish children between 6 months and 8 years
      of age: a cross-sectional radiological study. Authors' reply.

PMID- 24133744
TI  - Stent thrombosis following drug-eluting stents: conflict of generations.

PMID- 24133745
TI  - Author reply: To PMID 23813060.

PMID- 24133746
TI  - Insights and lessons useful to everyday practice.

PMID- 24133747
TI  - In response to: "Portability of licensure and the Nation's Health".

PMID- 24133748
TI  - In response to letter to the editor: Re: "Portability of licensure and the
      Nation's Health".

PMID- 24133749
TI  - In response to the following letters to the editor: "A paradox: Military Graduate
      Medical Education, an open letter to GME" (Mil Med 2012; 177(10): vi), "The real
      paradox: the case of the missing hat" (Mil Med 2012; 177(12): vii), "Letter to
      the editor" (Mil Med 2013; 178(1): iv-v), and "A paradox: Military Graduate
      Medical Education, one year later" (Mil Med 2013; 178(5): v).

PMID- 24133750
TI  - In response to: "Case reports: Death of active duty soldiers following ingestion
      of dietary supplements containing 1,3-dimethylamylamine (DMAA)" (Mil Med 2012;
      177(12): 1455-59).

PMID- 24133751
TI  - In response to letter to the editor: Re: "Case reports: Death of active duty
      soldiers following ingestion of dietary supplements containing 1,3
      dimethylamylamine (DMAA)" (Mil Med 2012; 177(12): 1455-59).

PMID- 24133752
TI  - Current world literature. Neuromuscular disease: muscle.

PMID- 24133753
TI  - Response: Re: The emergence of primary care in Latin America: reflections from
      the field.

PMID- 24133754
TI  - Response: Re: Journal of the American Board of Family Medicine issue on
      communities of solution.

PMID- 24133755
TI  - Chronic enteropathy and diet.

PMID- 24133756
TI  - Calcinosis cutis in relatives of Bulldogs.

PMID- 24133757
TI  - Osteopathic manual treatment and ultrasound therapy for chronic low back pain: an
      illustration of osteopathic semantic confusion. Author reply.

PMID- 24133758
TI  - International prostate symptoms score usage in a developing country.

PMID- 24133759
TI  - [Chronic gastric volvulus by diaphragmatic hernia and gastroparesis].

PMID- 24133760
TI  - [New paradigm for treatment of chronic hepatitis C virus infection].

PMID- 24133761
TI  - [The association between stomach cancer and colorectal cancer: it still remains
      unclear].

PMID- 24133762
TI  - Abstracts of the Third Cross-Cultural Health Care Conference: Collaborative and
      Multidisciplinary Interventions, February 8-9, 2013, Hawaii.

PMID- 24133763
TI  - [Invisible].

PMID- 24133764
TI  - [For bacteria, humans are just an animal].

PMID- 24133765
TI  - [An intimate bond].

PMID- 24133766
TI  - [How do you recognize good post-graduate education?].

PMID- 24133767
TI  - [Surveillance].

PMID- 24133768
TI  - [Prescribing antibiotics in a veterinary clinic].

PMID- 24133769
TI  - [Communication with the owner limits antibiotic prescriptions].

PMID- 24133770
TI  - [Responsible antibiotic use in the small animal practice. Bottlenecks and
      solutions].

PMID- 24133771
TI  - [Responsible antibiotic use: the role of business life].

PMID- 24133772
TI  - [Antibiotic use in special animals].

PMID- 24133773
TI  - [Reduction of antibiotics in the world].

PMID- 24133774
TI  - [Formulary dog and cat].

PMID- 24133775
TI  - [Castration of males decide per case].

PMID- 24133776
TI  - [Advising about animal welfare].

PMID- 24133777
TI  - [Coagulase-negative staphylococcus and mammae health].

PMID- 24133778
TI  - [An English bulldog with MRSP].

PMID- 24133779
TI  - [Hygiene protocol: clean, clear and easy].

PMID- 24133780
TI  - Expansion plan for hurricane evacuees.

PMID- 24133781
TI  - Public health perspective on causes of death among relatively young adults in a
      biracial (Black-white) semi-rural Louisiana community and implications for
      prevention: the Bogalusa Heart Study.

PMID- 24133782
TI  - Lifetime risks of cutaneous melanoma by histological subtype and race/ethnicity
      in the United States.
AB  - The probability of developing melanoma of the skin in the United States has been
      previously reported as a whole entity. This study aimed to describe lifetime
      risks of cutaneous melanoma by histological subtype among different racial and
      ethnic groups in the United States. Melanoma cases newly diagnosed in 2005-2007
      were obtained from 16 registries participating in the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program. Lifetime risks of
      developing melanoma subtypes (nodular melanoma, lentigo maligna melanoma,
      superficial spreading melanoma, acral lentiginous melanoma and desmoplastic
      melanoma) were examined among non-Hispanic whites, Hispanic whites, Blacks, and
      Asian/Pacific Islanders. Of the total 43,690 melanoma cases, 18,910 cases (43%)
      diagnosed with one of the five histological subtypes were included in the study.
      The results reveal that lifetime risks of melanoma subtypes differ among racial
      and ethnic groups, and therefore, stratification of the risks by subtype provides
      useful information in evaluating and counseling patients.

PMID- 24133783
TI  - A 33-year-old female with first episode of sudden onset massive hemoptysis.

PMID- 24133784
TI  - An eight-month-old infant with diarrhea and skin lesions.

PMID- 24133785
TI  - Oligosecretory biclonal multiple myeloma.
AB  - Among the plasma cell dyscrasias, non-secretory myeloma is one of the rarest.
      This diagnosis is based on the absence of monoclonal proteins in the serum and
      urine. When serum free light chains are trace and the kappa: lambda ratio normal,
      clonality may however be established by PCR. We present a case of an
      oligosecretory myeloma confirmed by PCR, which would have hitherto been
      classified as non-secretory.

PMID- 24133786
TI  - Sexually transmitted diseases during pregnancy in Louisiana, 2007-2009: high-risk
      populations and adverse newborn outcomes.
AB  - BACKGROUND: The aims of the study were to determine the prevalence of sexually
      transmitted diseases during pregnancy (STDs/P) in Louisiana, the association of
      maternal characteristics with STDs/P, and the association of STDs/P with low
      birth weight and preterm birth. METHODS: STDs surveillance data from 2006-2009
      were linked with 2007-2009 birth certificate data. The linked data were used for
      analyses. The data were limited to infections of chlamydia, gonorrhea, and
      syphilis during pregnancy. Logistic regression was applied to evaluate
      associations. RESULTS: The prevalence of chlamydia, gonorrhea, and syphilis
      during pregnancy was 5.5%, 1.6%, and 0.3%, respectively, among women who had a
      live birth between 2007 and 2009. Maternal race, ethnicity, age, education,
      marital status, and Medicaid paid for delivery were associated with STDs/P (p
      value < .05). Only infection with gonorrhea during pregnancy was associated with
      preterm birth [adjusted OR: 1.20 (CI95%: 1.08-1.33)]. CONCLUSIONS: The prevalence
      of STDs/P in Louisiana remains high. Low-educated, young, black, single, and
      economically disadvantaged mothers were at high risk for STDs during pregnancy.
      Women diagnosed with gonorrhea during pregnancy were more likely to experience
      preterm birth.

PMID- 24133787
TI  - ECG of the month. ECG in a cyanotic 22-year-old woman who had a cardiac operation
      in early childhood. Normal sinus rhythm; biatrial enlargement; right axis
      deviation of the QRS complex; biventricular enlargement with repolarization
      abnormality.

PMID- 24133788
TI  - Radiology case of the month. A child with progressive enlargement of the left
      foot. Macrodystrophia lipomatosa.

PMID- 24133789
TI  - A 52-year-old man with ecchymotic leg ulcers.

PMID- 24133790
TI  - Fatality following acute onset of shortness of breath.

PMID- 24133791
TI  - Changing birth practices.

PMID- 24133793
TI  - Cytotec and the FDA.

PMID- 24133792
TI  - Marion's message. Risks in being born.

PMID- 24133794
TI  - The times and tools of induction.

PMID- 24133796
TI  - Should we ban labor induction?

PMID- 24133795
TI  - Herbs for induction of labor.

PMID- 24133797
TI  - Timing is everything.

PMID- 24133798
TI  - An emotional preparation for birth.

PMID- 24133799
TI  - The circumcision conversation.

PMID- 24133800
TI  - Jane Sharp: a midwife of Renaissance England.

PMID- 24133801
TI  - The mythical expiration date.

PMID- 24133802
TI  - The episiotomy redemption.

PMID- 24133803
TI  - Cesarean inter-section.

PMID- 24133804
TI  - Maharishi Ayurveda for postpartum care.

PMID- 24133805
TI  - The downside of doula-ing.

PMID- 24133806
TI  - Resolving shoulder dystocia: is episiotomy best practice?

PMID- 24133807
TI  - Rotary helps pave the way for the Mongolian maternal health training project.

PMID- 24133808
TI  - Searching for ancient secrets in childbirth.

PMID- 24133809
TI  - My successful homebirth after five cesareans.

PMID- 24133810
TI  - H.R. 2286: A vision to increase maternal health professionals & services.

PMID- 24133811
TI  - My discovery of the historical Dr. Joseph DeLee.

PMID- 24133813
TI  - Labor encouragement with essential oils.

PMID- 24133812
TI  - An estimated due season.

PMID- 24133814
TI  - Rebirth.

PMID- 24133816
TI  - What have you learned in animal birth that has helped you in understanding human
      birth?

PMID- 24133815
TI  - 15 days late: oh, the pressure!

PMID- 24133817
TI  - Nurture all women and never devalue their birth experience.

PMID- 24133818
TI  - Announcing a new series: Understanding unusual dysproteinemias.

PMID- 24133819
TI  - Oral oncolytics: part 1--financial, adherence, and management challenges.

PMID- 24133820
TI  - Use of molecular biomarkers to inform adjuvant therapy for colon cancer.
AB  - The decision about who may derive benefit from adjuvant chemotherapy in colon
      cancer is often a difficult one for clinicians. While multiple trials have
      demonstrated that adjuvant chemotherapy reduces the risk of recurrence and
      improves overall survival in patients with stage III disease, the data supporting
      the use of adjuvant chemotherapy in patients with stage II disease are not as
      compelling. Because adjuvant therapy can have significant toxicity, tools to help
      clinicians determine who may derive a benefit from therapy are of the utmost
      importance. Recent advances in high throughput technologies have led to the
      identification of molecular biomarkers-including microsatellite instability
      (MSI), loss of heterozygosity (LOH), p53, Kirsten rat sarcoma viral oncogene
      homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF),
      thymidylate synthase (TS), and excision repair cross-complementation group 1
      (ERCC1)--as well as various multigene assays that are being studied for their
      ability to offer both prognostic and predictive information to clinicians. Here
      we review the current knowledge about molecular biomarkers that may aid the
      clinician in offering personalized cancer therapy based on the genetic landscape
      of an individual patient's tumor.

PMID- 24133821
TI  - Personalized medicine in the adjuvant chemotherapy of stage II colon cancer--are
      we there yet?

PMID- 24133822
TI  - Biomarkers in colon cancer: the chasm between expectations and reality.

PMID- 24133823
TI  - Straightforward oncology: How honest is the EMR?

PMID- 24133824
TI  - Musings of a cynical curmudgeon: Pain or feign?

PMID- 24133825
TI  - First-line treatment for patients with CML in chronic phase: why imatinib is an
      appropriate choice.

PMID- 24133826
TI  - First-line treatment for patients with CML in chronic phase: second-generation
      TKIs are the therapy of choice.

PMID- 24133827
TI  - ACR Appropriateness Criteria: Localized nodal indolent lymphoma.
AB  - The present guidelines review epidemiology, pathology, presentation, workup,
      staging, prognostic factors, and treatment options for patients with localized
      nodal indolent lymphoma, with an emphasis on radiation guidelines, including
      radiation dose, field design, and radiation techniques. Following a discussion of
      the current literature and available data for treatment and outcomes of patients
      with indolent lymphoma, several different example cases are reviewed to help
      physicians make appropriate treatment decisions. The American College of
      Radiology 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) by which the panel rates
      the appropriateness of imaging and treatment procedures. In those instances where
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment.

PMID- 24133828
TI  - Ductal carcinoma in situ of the breast: 'making the punishment fit the crime'.

PMID- 24133829
TI  - Unusual myelomas: a review of IgD and IgE variants.
AB  - Immunoglobulin D multiple myeloma (IgD MM) accounts for almost 2% of all myeloma
      cases. It is associated with an increased frequency of undetectable or small
      monoclonal (M)-protein levels on electrophoresis; osteolytic lesions;
      extramedullary involvement; amyloidosis; a lambda (lambda) light chain
      predilection; renal failure; hypercalcemia; and, often, advanced disease at
      diagnosis. Immunoglobulin E (IgE) MM is rare, with fewer than 50 cases reported
      in the literature. IgE MM presents with features similar to those of IgD MM,
      along with a higher incidence of plasma cell leukemia. The hallmark of IgE MM is
      t(11;14) (q13;q32). IgD and IgE levels are generally very low and hence may
      escape detection; thus, it is important that, when myeloma is suspected, patients
      be screened for the presence of IgD and IgE if they have an apparently free
      monoclonal immunoglobulin light chain in the serum. Although survival of patients
      with IgD MM or IgE MM is shorter in comparison to those with immunoglobulin G
      (IgG) MM or immunoglobulin A (IgA) MM, the outcome for patients with IgD and IgE
      subtypes is improving with the use of novel agents and autologous
      transplantation.

PMID- 24133830
TI  - IgD and IgE variants of myeloma: valuable insights and therapeutic opportunities.

PMID- 24133831
TI  - Rare myelomas: sometimes when you hear hooves, it's a zebra...

PMID- 24133832
TI  - Study links omega-3 fatty acids and prostate cancer risk.

PMID- 24133833
TI  - FDA approves afatinib for advanced lung cancer.

PMID- 24133834
TI  - EUTOS score validated for predicting treatment outcomes with TKI therapy.

PMID- 24133835
TI  - The impact of molecular testing on treatment of cancer of unknown primary origin.

PMID- 24133836
TI  - Nonseminomatous germ cell tumor of testis and interrupted treatment.

PMID- 24133837
TI  - Gauging the impact of ESRD treatments.

PMID- 24133838
TI  - The times they are a changin'.

PMID- 24133839
TI  - The CMO Initiative: Creating an open dialogue on improving dialysis care. Part I:
      Nutrition.

PMID- 24133840
TI  - Patient-physician relationships: The day I realized...

PMID- 24133841
TI  - Partnering with your doctors can help you manage your kidney disease.

PMID- 24133842
TI  - Dealing with phosphorus: a patient perspective.

PMID- 24133843
TI  - Transplantation: what every patient and health care professional should know.

PMID- 24133844
TI  - A note on reporting sedation scores (Re: "Propofol compared with combination
      propofol for midazolam/fentanyl for endoscopy in a community setting, " February
      2013, ANNA Journal, Vol 81, No. 1).

PMID- 24133846
TI  - Response from the Editor-in-Chief.

PMID- 24133845
TI  - Author's reply: To PMID 23513321.

PMID- 24133847
TI  - To press or not to press, and if so, with what? A single question-focused meta
      analysis of vasopressor choice during regional anesthesia in obstetrics.
AB  - Given the underlying assumption that reasonable maternal hemodynamics can be
      achieved with either ephedrine or phenylephrine, this focused meta-analysis
      addresses the impact of vasopressor choice on resultant neonatal Apgar scores
      during regional anesthesia. The literature was systematically searched for
      randomized trials of obstetric vasopressor use employing standard search tools.
      Only the highest quality trials were included. Of 142 studies retrieved, 9 met
      the defined inclusion criteria. Apgar scores at 1 and 5 minutes in the ephedrine
      group (served as control) vs the phenylephrine group did not differ at either
      time epoch; no abnormal values prevailed in either group (relative risk, 0.88;
      CI, 0.79-1.16). This meta-analysis focused on the most clinically relevant,
      immediately available information pertinent in the obstetric suite, the Apgar
      score, and found that ephedrine and phenylephrine did not differ in their effect
      on this metric. The current meta-analysis provides an updated, evidence-based
      validation of vasopressor use from the American Society of Anesthesiologists'
      2007 "Practice Guidelines for Obstetric Anesthesia".

PMID- 24133848
TI  - Detection of pneumothorax with ultrasound.
AB  - Diagnosis of a pneumothorax in the perioperative area can be difficult.
      Traditional gold-standard modalities may not be available or feasible to
      institute. Ultrasound guidance allows the anesthesia provider a method of quickly
      ruling out this potentially life-threatening complication. In this article we
      detail the use of sonography for fast and accurate diagnosis of pneumothorax. The
      essential terms relative to the use of ultrasonography to detect pneumothorax are
      also defined.

PMID- 24133849
TI  - Forced-air warming design: evaluation of intake filtration, internal microbial
      buildup, and airborne-contamination emissions.
AB  - Forced-air warming devices are effective for the prevention of surgical
      hypothermia. However, these devices intake nonsterile floor-level air, and it is
      unknown whether they have adequate filtration measures to prevent the internal
      buildup or emission of microbial contaminants. We rated the intake filtration
      efficiency of a popular current-generation forced-air warming device (Bair Hugger
      model 750, Arizant Healthcare) using a monodisperse sodium chloride aerosol in
      the laboratory. We further sampled 23 forced-air warming devices (same model) in
      daily hospital use for internal microbial buildup and airborne-contamination
      emissions via swabbing and particle counting. Laboratory testing found the intake
      filter to be 63.8% efficient. Swabbing detected microorganisms within 100% of the
      forced-air warming blowers sampled, with isolates of coagulase-negative
      staphylococci, mold, and micrococci identified. Particle counting showed 96% of
      forced-air warming blowers to be emitting significant levels of internally
      generated airborne contaminants out of the hose end. These findings highlight the
      need for upgraded intake filtration, preferably high-efficiency particulate air
      filtration (99.97% efficient), on current-generation forced-air warming devices
      to reduce contamination buildup and emission risks.

PMID- 24133850
TI  - Use of a positive pressure endoscopic mask to assist with positive pressure
      ventilation in a morbidly obese patient during fiberoptic intubation: a case
      report.
AB  - Airway management in the morbidly obese, anesthetized patient can be especially
      challenging. Difficulties in fiberoptic intubation (FOI) can be experienced due
      to alterations in airway anatomy associated with morbid obesity and the effects
      of anesthesia. The loss of upper airway muscle tone that occurs during anesthesia
      compromises the structure of the pharynx, causing a tendency toward airway
      collapse. This collapsibility can prevent the identification of anatomical
      structures during FOI, making this advanced airway technique difficult or
      impossible. The application of positive pressure via endoscopic mask ventilation
      during FOI can help to stent open collapsible airways and reestablish airway
      anatomy in morbidly obese patients. Although drawbacks exist, the endoscopic mask
      may be most effective at accomplishing this goal.

PMID- 24133851
TI  - Pediatric posttransplant anesthesia: a summary review of the literature with
      recommendations for clinical practice.
AB  - Premature pediatric patients who previously received a multivisceral organ
      transplant and subsequently present for nontransplant surgery will offer multiple
      challenges to the anesthesia practitioner caring for the patient during the
      operative period. Multivisceral organ transplant is a treatment option for
      patients with irreversible intestinal and hepatic failure. Physiologic
      complications of this population include bronchopulmonary dysplasia, reactive
      airway disease, and delayed gastric motility. Because of prolonged
      hospitalization and chronic illness, this population frequently is difficult to
      achieve peripheral venous access. Immunosuppressive medications may result in
      lymphoproliferation of the airway, increased risk of infection, alterations in
      organ system function, and the need to ensure continuation of scheduled
      immunosuppression therapy. The posttransplant pediatric patient has been exposed
      to prolonged periods of sedation while in the intensive care unit, resulting in
      pharmacodynamic tolerance to common anesthetic medications. A review of the
      current literature in the management of this challenging patient population is
      presented.

PMID- 24133852
TI  - Perioperative changes in oxygen saturation after ambulatory laparoscopic
      cholecystectomy: a retrospective analysis.
AB  - In the ambulatory surgical setting, patients may present with grossly abnormal
      oxygen saturation (Spo2) readings that, along with other disease pathology, make
      referral to an inpatient facility a straightforward decision. Patients presenting
      with unexplained slightly abnormal Spo2 readings might make evaluation as an
      appropriate candidate for the ambulatory setting more problematic. Little
      guidance is provided for these scenarios in current consensus documents, and
      minimal data exist regarding preoperative baseline Spo2 readings as a predictor
      for postoperative Spo2 readings after undergoing general anesthesia and surgery
      in the ambulatory care setting. A retrospective analysis was performed of all
      laparoscopic cholecystectomies performed at a freestanding ambulatory surgery
      center during 2011 (n = 56). Multiple linear regression analysis was performed to
      establish predictors for variability in baseline Spo2. Wilcoxon tests were used
      to compare preoperative baseline Spo2 readings with readings taken at discharge.
      Increased patient age was the only statistically significant predictor of lower
      baseline Spo2 levels, although no statistically significant decrease in Spo2 was
      found at discharge in patients above 60 years old. Males, patients who smoke, and
      patients whose body mass index exceeded 30 kg/m2 all demonstrated statistically
      significant decreases in Spo2 values at discharge home (Z = -1.947, -1.807, 
      1.75, P < .05).

PMID- 24133853
TI  - Severe pulmonary hypertension: a noncardiac, nonobstetric surgical case study.
AB  - This report describes the noncardiac, nonobstetric surgical case of a 29-year old
      woman with idiopathic pulmonary arterial hypertension. To safely manage a patient
      with pulmonary hypertension, the anesthesia provider must have a thorough
      understanding of the disease and associated risks. This case study briefly
      summarizes the surgical case and then discusses history, current classifications,
      epidemiology, pathophysiology, contemporary treatments, and basic anesthetic
      management related to pulmonary hypertension.

PMID- 24133854
TI  - Epidural anesthesia for cesarean delivery facilitated by minimally invasive
      hemodynamic monitoring in a patient with Fontan repair: a case report.
AB  - With the advancement of medicine, surgery, and technology, along with the decline
      in mortality, anesthesia providers encounter patients with complex and rare
      conditions. One such example is the single ventricle congenital cardiac defect,
      which is corrected with Fontan reconstructive surgery. To care for patients who
      have undergone the Fontan procedure, the anesthesia provider needs an in-depth
      knowledge of the anatomy and physiology behind Fontan circulation. This article
      presents a brief overview of the anatomy and physiology of Fontan circulation.
      The case report describes a parturient who, approximately 2 decades earlier, had
      undergone a Fontan operation at the age of 4 years and recovered uneventfully.
      This article discusses the anesthetic management for the patient during cesarean
      delivery using epidural anesthesia, and the minimally invasive monitoring
      technology (Vigileo monitor, Edwards Lifesciences) to assist in monitoring the
      patient intraoperatively.

PMID- 24133856
TI  - Every hour counts: Integrating rapid molecular analysis with antimicrobial
      stewardship in real time for gram-negative bacteremia.

PMID- 24133857
TI  - Rapid testing for CVDs: high-sensitivity troponin assays.

PMID- 24133855
TI  - AANA journal course: update for nurse anesthetists--Part3--Tobacco smoking using
      a waterpipe (hookah): what you need to know.
AB  - Smoking tobacco using a waterpipe (hookah) is increasing worldwide and is
      remarkably common among adolescents and young adults in the United States.
      Contrary to misperceptions that waterpipe tobacco smoking presents fewer health
      risks than cigarette smoking, recent data demonstrate clearly that the smoke from
      a waterpipe contains many of the same toxicants that are in cigarettes, including
      the dependence-producing drug nicotine, cancer-causing polycyclic aromatic
      hydrocarbons, pulmonary disease-causing volatile aldehydes, and cardiovascular
      disease-causing carbon monoxide that can also lead to acute intoxication in
      waterpipe users. Because many anesthesia providers are likely treating waterpipe
      tobacco smokers, the goal of this AANA Journal Course is to describe a waterpipe,
      who uses a waterpipe to smoke tobacco, and the toxicants found in waterpipe smoke
      and waterpipe smokers. Based on available evidence, there is no indication that
      waterpipe tobacco smoking is any less risky to patient health than cigarette
      smoking. Anesthesia providers should begin to assess patients for this form of
      tobacco use explicitly and should consider addressing it as they do cigarette
      smoking, with the additional precaution of presurgery carboxyhemoglobin
      measurement.

PMID- 24133858
TI  - Dry hematology: its development, function, and role in point of care testing.

PMID- 24133859
TI  - Allowable measurement error associated with quality management plans.

PMID- 24133860
TI  - The technology is there: options for preventing lab labeling and tracking errors.

PMID- 24133861
TI  - Achieving 100% accountability: How healthcare CRM drives action and resolves
      issues.

PMID- 24133862
TI  - Assessing the impact of new cervical cancer screening guidelines.

PMID- 24133863
TI  - Multiplex molecular diagnostics: shifting the paradigm.

PMID- 24133864
TI  - DNA replication: polymerases.

PMID- 24133865
TI  - Safe for now.

PMID- 24133866
TI  - Three essential strategies for a successful lab design.

PMID- 24133868
TI  - "Empty QC".

PMID- 24133869
TI  - "Empty QC".

PMID- 24133870
TI  - Automated urinalysis in the clinical lab.

PMID- 24133871
TI  - Another clue to foil a wily enemy: measuring protein tumor markers outside the
      primary tissue in breast carcinoma.

PMID- 24133872
TI  - The future of imaging technology in the science of pathology.

PMID- 24133873
TI  - Trends for early detection of aneuploidy and trisomy.

PMID- 24133874
TI  - Automation and beyond: improving efficiency in the pathway from collection to
      care.

PMID- 24133875
TI  - HAI prevention and control: rapid MRSA screening methods.

PMID- 24133876
TI  - DNA and RNA structure: nucleic acids as genetic material.

PMID- 24133877
TI  - Outreach strategies for operational success.

PMID- 24133878
TI  - Anatomic pathology today and tomorrow.

PMID- 24133880
TI  - Firing the soul.

PMID- 24133881
TI  - Through a lens brightly: How a St. Paul physician mixes movie-making and
      medicine.

PMID- 24133882
TI  - Tapping the creative side: Mayo Clinic turns its arts focus toward those who care
      for patients.

PMID- 24133883
TI  - Artists in residence: Hospitals in Minneapolis and Fargo have hired artists to
      help cancer patients deal with the stress of treatment.

PMID- 24133884
TI  - Medical students at play: A look at some of this year's Fisch Art of Medicine
      Award winners.

PMID- 24133886
TI  - Their best shot: The winners of our third annual photo contest.

PMID- 24133885
TI  - A decade of musings.

PMID- 24133887
TI  - Getting the word out on MNsure: The many facets of promoting the new health
      insurance exchange.

PMID- 24133888
TI  - A few minutes with Kathryn Duevel, M.D., MNsure board member.

PMID- 24133889
TI  - Cirque de-Stress.

PMID- 24133890
TI  - Healing through reflective writing: Breast cancer survivors' experience.
AB  - This article describes an intervention for breast cancer survivors called Journal
      of My Medical Experiences in which participants engaged in reflective writing
      over six weeks. The 107 participants were encouraged to explore concerns and
      issues in a safe online environment. About half of the women posted writings to a
      website once a week or more; others logged on solely to read what others had
      written. A number of themes emerged as the women explored their feelings. We
      share some of those.

PMID- 24133891
TI  - Skin-lightening practices and mercury exposure in the Somali community.
AB  - Somali women often use creams and soaps to lighten skin tone, fade freckles or
      get rid of age spots. Use of these products raises a health concern, as some have
      been found to contain mercury. This article describes an investigation that
      involved interviewing Somali women about skin-lightening practices and the
      products they use and then testing those products for mercury. Twenty-seven
      samples of products purchased at markets in Minneapolis and St. Paul were
      analyzed bythe Minnesota Department of Health for specific mercury levels. Eleven
      of the 27 (47%) were found to contain mercury. Some exceeded the current FDA
      threshold of 1 part per million. This has prompted both state and federal health
      officials to issue warnings about the use of these products.

PMID- 24133892
TI  - Homo sapiens as physician and patient: a view from Darwinian medicine.
AB  - Medicine's cardinal diagnostic and therapeutic resource is the clinical
      encounter. Over the last two centuries and particularly over the last five
      decades the function of the clinical encounter has been eroded to the point of
      near irrelevance because of the atomized and atomizing influence of technology
      and microspecialization. Meanwhile, over the past five decades the exceptionalist
      view of Homo sapiens inherent in the social and religious traditions of the West
      has similarly undergone radical changes. H. sapiens is now best understood as a
      microecosystem integrated into a much broader ecosystem: the biosphere. That
      human microecosystem is composed of constituents derived from the archaeal,
      bacterial, and eukaryan domains via endosymbiotic, commensalistic and mutualistic
      interactions. This amalgamation of 100 trillion cells and viral elements is
      regulated by a composite genome aggregated over the 3.8 billion years of
      evolutionary history of organic life. No component of H. sapiens or its genome
      can be identified as irreducibly and exclusively human. H. sapiens' humanity is
      an emergent property of the microecosystem. Ironically as H. sapiens is viewed by
      evolutionary science in a highly integrated manner medicine approaches it as a
      balkanized, deaggregated entity through the eye of 150 different specialties. To
      effectively address the needs of H sapiens in its role as patient by the same
      species in its role as physician the disparate views must be harmonized. Here I
      review some conceptual elements that would assist a physician in addressing the
      needs of the patient in integrum, as a microecosystem, by the former address the
      latter as a historical gestalt being. The optimal way to recover the harmony
      between patient and physician is through a revitalization of the clinical
      encounter via an ecological and Darwinian epistemology.

PMID- 24133893
TI  - Child maltreatment in Puerto Rico: findings from the 2010 National Child Abuse
      and Neglect Data System.
AB  - OBJECTIVE: Child maltreatment can have long-term adverse effects. Quantifying the
      scope and characteristics of child maltreatment is necessary for effective
      prevention in Puerto Rico. METHODS: The National Child Abuse and Neglect Data
      System Child File contains all the reports of child maltreatment from the United
      States (US) and Puerto Rico. A child maltreatment victim is defined as a child
      whose maltreatment was substantiated or indicated by the local child protective
      agency. We compared reporting and victimization rates and reporting sources in
      Puerto Rico, with those in the US and examined characteristics of child
      maltreatment in Puerto Rico. RESULTS: During 2006-2010, a total of 31,849-40,712
      cases of child maltreatment were reported annually in Puerto Rico. Victimization
      rates are consistently higher in Puerto Rico than in the US (10.7/1,000
      14.8/1,000 in Puerto Rico vs. 10.1/1,000-12.1/1,000 in the US), despite
      consistently lower reporting rates. In 2010, victimization rates were highest
      among children aged 1-6 years. In Puerto Rico, neglect is the most common form of
      maltreatment, followed by emotional abuse; however, the majority of victims
      suffered multiple types of abuse. Reporting was more commonly anonymous in Puerto
      Rico (29.8%) than in the US (9.4%) and less commonly provided by professionals in
      Puerto Rico (37.2%) than in the US (58.7%). CONCLUSION: We identified a high
      prevalence of child maltreatment in Puerto Rico. A lower reporting rate, higher
      victimization rate, and substantial percentage of anonymous reporting indicate
      potential underreporting of child maltreatment in Puerto Rico. Increasing the
      awareness and training professionals for improved child maltreatment
      identification could help alleviate the problem of underreporting.

PMID- 24133894
TI  - Association between obesity and symptoms of depression of adults in Puerto Rico.
AB  - OBJECTIVE: This study was aimed at determining the prevalence of overweight; of
      class 1 and class 2/3 obesity; and of the symptoms of depression in adults in
      Puerto Rico. The study also evaluated the relationship between the symptoms of
      depression and weight status. METHODS: The sample for this study consists of
      6,025 adults (3,851 females and 2,174 males) who lived in Puerto Rico at the time
      of and who participated in either the 2006 or the 2010 BRFSS. RESULTS: In this
      sample 70.0% of the respondents were either overweight or obese. About 39.6% of
      them were considered overweight, while 18.1% were obese class 1 and 12.3% were
      obese class 2 or 3. When compared by gender, the prevalence rate of overweight
      was higher for males (46.9%) than it was for females (35.5%), but females (14.1%)
      had a higher rate of class 2/3 obesity than did males (9.2%). There were no
      significant gender-based differences in the class 1 (BMI between 30 and 35)
      obesity group. According to the study's findings, depression symptoms and class 1
      obesity are not strongly associated. A positive relationship between depression
      and weight was found only in women with class 2/3 obesity (BMI>35). CONCLUSION:
      In summary, the results of this study show that depressive symptoms are
      associated with obesity, and this correlation seems to be more significant in
      women, especially those with severe obesity, less education, and lower incomes.
      Findings point to the existence of a high risk of comorbid obesity and depression
      of adults in Puerto Rico.

PMID- 24133895
TI  - Incidence, in-hospital case-fatality rates, and management practices in Puerto
      Ricans hospitalized with acute myocardial infarction.
AB  - OBJECTIVE: There are extremely limited data on minority populations, especially
      Hispanics, describing the clinical epidemiology of acute coronary disease. The
      aim of this study is to examine the incidence rate of acute myocardial infarction
      (AMI), in-hospital case-fatality rate (CFR), and management practices among
      residents of greater San Juan (Puerto Rico) who were hospitalized with an initial
      AMI. METHODS: Our trained study staff reviewed and independently validated the
      medical records of patients who had been hospitalized with possible AMI at any of
      the twelve hospitals located in greater San Juan during calendar year 2007.
      RESULTS: The incidence rate (# per 100,000 population) of 1,415 patients
      hospitalized with AMI increased with advancing age and were significantly higher
      for older patients for men (198) than they were for women (134). The average age
      of the study population was 64 years, and women comprised 45% of the study
      sample. Evidence-based cardiac therapies, e.g., aspirin, beta blockers, ACE
      inhibitors/angiotensin receptor blockers, and statins, were used with 60% of the
      hospitalized patients, and women were less likely than men to have received these
      therapies (59% vs. 65%) or to have undergone interventional cardiac procedures
      (47% vs. 59%) (p<0.05). The in-hospital CFR increased with advancing age and were
      higher for women (8.6%) than they were for men (6.0%) (p<0.05). CONCLUSION:
      Efforts are needed to reduce the magnitude of AMI, enhance the use of evidence
      based cardiac therapies, reduce possible gender disparities, and improve the
      short-term prognoses of Puerto Rican patients hospitalized with an initial AMI.

PMID- 24133896
TI  - Social support and its association with sociodemographic characteristics, dietary
      patterns, and perceived academic stress among college students in Puerto Rico.
AB  - OBJECTIVE: The objective of the present study was to determine the association
      between social support, dietary pattern, and academic stress among college
      students in Puerto Rico, based on their socio-demographic characteristics.
      METHODS: This was a retrospective, descriptive, epidemiological study that used a
      stratified sample of 275 college students. The data collection was done by means
      of a self-administered instrument. RESULTS: Most of the participating students
      were female (67.6%), ranged in age from 21 to 30 years (88%), and had health
      weights (56.4%); a large minority, 42.7%, lived in homes having low annual
      incomes. Most of the participating students perceived their academic loads as
      being heavy (68.2%) and their total academic stress levels as being moderate
      (60.7%). Most of the students had moderate levels of social support (61.5%).
      Social support was significantly associated with age (p = 0.04), in that young
      students had high levels of social support; with the school being attended (p =
      0.01), in that students from the School of Dental Medicine had high levels of
      social support' and with perceived academic load (p = 0.02). Social support was
      significantly associated with age (p = 0.04), in that the younger students had
      higher levels of social support than did their older counterparts; with the
      school being attended (p = 0.01), in that students from the School of Medicine
      had higher levels of social support than did the students from the other schools;
      and with perceived academic load (p = 0.02). CONCLUSION: There were associations
      between social support and age, school, and perceived academic load, but there
      were no such associations between social support and either level of academic
      stress or dietary pattern.

PMID- 24133897
TI  - Fetal surface placental hematomas: the clue in the diagnosis of a bleeding
      dyscrasia.
AB  - Von Willebrand disease (vWD) is the most common inherited bleeding disorder in
      humans, occurring in about 1% of women and caused by a deficiency or abnormality
      in the von Willebrand factor (vWF). There are different types of vWD. Type I
      comprises approximately 80% of the cases, its inheritance is autosomal dominant.
      Women with vWD have a 10-fold risk of having antepartum bleeding when compared to
      the general population. We report a case of von Willebrand disease diagnosed due
      to findings on a routine ultrasound evaluation.

PMID- 24133898
TI  - Analytical performances and heart failure research of the BNP and NT-proBNP
      assays on the Cobas E601 and ADVIA Centaur.
AB  - BACKGROUND: The analytical performances of the NT-proBNP and BNP assays on the
      Cobas E601 and ADVIA Centaur were thoroughly evaluated. In addition, the values
      of BNP and NT-proBNP, which are heart failure markers, were compared in the
      diagnosis of HF patients with or without acute cerebral infarction since they
      could also be elevated in ischemic stroke. METHODS: Clinical and Laboratory
      Standards Institute (CLSI) documents were employed in the analytical evaluation
      of NT-proBNP and BNP assays on the Cobas E601 and ADVIA Centaur. Then 100 heart
      failure patients and 103 cerebral infarction complicated with heart failure
      patients, who had been diagnosed by clinical doctors blinded to NT-proBNP and BNP
      concentrations, were chosen to compare their values in the diagnosis of heart
      failure with or without acute cerebral infarction. RESULTS: The NT-proBNP and BNP
      methods are precise and accurate (total CV < 2.9%, deviation < 3.6%), have wide
      dynamic measuring ranges (8 pg/mL to 35 126 pg/mL and 2.0 pg/mL to 5094 pg/mL,
      respectively) with maximum dilutability of 1:2, and are free of common
      interferences. The most suitable sample types for NT-proBNP and BNP are serum and
      EDTA plasma, respectively, and both methods correlate well in simple-HF patients.
      Unlike BNP, the level of NT-proBNP is much higher in HF patients with acute
      cerebral infarction (p < 0.001). The Cobas E601 and ADVIA Centaur systems have
      good analytical performances. CONCLUSIONS: In HF patients with acute cerebral
      infarction, the NT-proBNP and BNP levels did not correlate and thus had
      implications for clinical diagnosis.

PMID- 24133899
TI  - Accuracy of self monitoring blood glucose systems in a clinical setting:
      application of new planned ISO- standards.
AB  - BACKGROUND: The accuracy of glucose meters (GMs) for self-monitoring of blood
      glucose (BG) is essential for preventing insulin dosage errors in insulin
      injecting diabetic patients. We evaluated the accuracy of 19 commercially
      available GMs in a clinical setting applying the new planned ISO criteria.
      METHODS: Capillary blood was taken at 10-minute intervals in insulin dependent
      patients during induction of a BG increase and decrease by administration of a
      standardized carbohydrate rich meal and/or injection of an appropriate dosage of
      insulin under medical supervision. BG was measured simultaneously by GMs and a
      laboratory method (Hitado Super GL). The GM results were compared with a
      laboratory reference method according to the current ISO criteria (ISO
      15197:2003) and the proposed (more stringent) criteria. RESULTS: Evaluating GM
      results according to the current ISO criteria, all GMs reached the minimum
      acceptable system accuracy criteria. Analysing GM results according to the more
      stringent planned ISO standard criteria, only 8 of 19 GMs reached the minimum
      acceptable accuracy criteria, i.e. > or = 95% of the individual glucose results
      fell within +/- 15 mg/dL of the results of the reference value at glucose
      concentrations < 100 mg/dL and within +/- 15% at glucose concentrations > or =
      100 mg/dL. When results obtained in BG ranges < and > or = 100 mg/dL were
      separately analysed, readings of 10 and 8 GMs, respectively, fell in the area of
      acceptable accuracy. CONCLUSIONS: The study shows that more than half of the
      tested GMs would fail the proposed tighter ISO criteria. Most GMs reveal similar
      accuracy in BG measurement when compared at lower and higher BG ranges.

PMID- 24133900
TI  - Heparin-induced thrombocytopenia in Chinese patients: 240 patients study in one
      center.
AB  - BACKGROUND: The study was conducted in order to analyze the incidence of heparin
      induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and
      thrombosis syndrome (HITTS) in 240 patients from the Department of Vascular
      Surgery in China, to evaluate the current laboratory detection technique, and to
      explore the feasibility for the technique to be developed in China. METHODS: 240
      patients receiving unfractionated heparin (UFH) were studied in one center.
      Before and after the UFH treatment, platelet count, HIT-antibody ELISA test, and
      heparin-induced platelet aggregation (HIPA) were tested. RESULTS: Among 240
      patients, HIT was diagnosed in 36 cases. The incidence was 15%. HITTS occurred in
      6 cases (2.5%). The median time of thrombocytopenia was the 8th day. Platelet
      counts recovered to normal level in 3 - 6 days after heparin withdrawal
      CONCLUSIONS: The incidence of HIT is higher; however, the incidence of HITTS is
      lower. Monitoring platelet count, which is simple and easy to do and available in
      hospitals at different levels (township hospital included), is a reliable method
      to diagnose HIT early. The HIT-antibody ELISA test could be introduced in
      specific hospitals to prescreen HIT. In view of the higher sensitivity and
      specificity of HIPA, it can be used in larger diagnostic centers in all the big
      cities of China.

PMID- 24133901
TI  - Association between the polymorphism of estrogen receptor alpha and Alzheimer's
      disease in Chinese population.
AB  - BACKGROUND: To investigate the possible association between the polymorphism of
      estrogen receptor alpha (ERalpha) and Alzheimer's disease (AD) in Chinese
      population. METHODS: Cognitive function of patients with AD was evaluated with
      the Modified Mini-Mental Status Examination (MMSE). ERalpha polymorphism was
      detected in 236 AD patients and 236 control individuals. Logistic regression was
      used in age, body mass index, education, depression, hypertension, diabetes,
      history of stroke, smoking status, ApoE e4 carrier, and estrogen receptor a
      genotypes to calculate their odds ratios. RESULTS: There were no significant
      differences in PvuII allele and genotype between AD patients and control
      individuals. The frequencies of XbaI x allele and XbaI xx genotype were
      significantly higher in AD patients than in control individuals (chi2 = 28.116,
      df = 1, p < 0.0001 and chi2 = 16.628, df = 2, p < 0.0001, respectively). The odds
      ratio for the patients with xx genotype was 2.12 (95% CI = 1.63 - 2.76, p <
      0.01). CONCLUSIONS: These findings suggest that ERalpha XbaI polymorphism is
      associated with an increased risk of AD in Chinese population. More research is
      needed to determine the mechanism by which ERalpha polymorphisms is associated
      with AD.

PMID- 24133902
TI  - Ischemic-type biliary lesions after liver transplantation: a retrospective
      analysis of risk factors and outcome.
AB  - BACKGROUND: Ischemic-type biliary lesions (ITBL) are the most troublesome
      complications after liver transplantation. Their cause remains unknown and,
      although some risk factors have been identified, results from different research
      groups are often conflicting. The goal of this study was to investigate potential
      risk factors for ITBL. METHODS: 565 transplantations performed between September
      1997 and August 2010 were identified and divided into two cohorts: 77 in which
      the patient developed ITBL and 488 in which no ITBL occurred. The following
      factors were analyzed: donor age, patient Child-Pugh score, cold ischemia time,
      total ischemia time, type of perfusion solution, shipped versus non-shipped
      organ, ABO-compatibility versus identity between donor and recipient, Rhesus
      difference versus identity between donor and recipient, presence versus absence
      of HLA antibodies in the patient at the time of registration on the transplant
      waiting list, presence in the donor of at least one HLA-C group 1 allele versus
      at least one HLA-C group 2 allele. HLA-C is the major inhibitory ligand for
      killer immunoglobulin-like receptors (KIR) that regulate the cytotoxic activity
      of natural killer cells. HLA-C alleles can be allocated into two groups, HLA-C1
      and HLA-C2, based on their KIR specificity. RESULTS: In a multivariate logistic
      regression analysis the donor age and patient Child-Pugh score C were found to be
      independent risk factors for ITBL (p < 0.001 and 0.007, respectively). However,
      the multivariate Cox regression analysis indicated that neither has an impact on
      graft survival. CONCLUSIONS: Donor age and patient Child-Pugh score predispose to
      ITBL, whereas other factors must intervene for their development.

PMID- 24133903
TI  - Diagnostic value of serum adenosine deaminase activity in HIV infected patients
      of Kurdish population.
AB  - BACKGROUND: Adenosine deaminase (ADA) is a hydrolytic enzyme involved in the
      deamination of adenosine to inosine. ADA is involved in T-lymphocyte
      differentiation and development. This study was aimed to determine the diagnostic
      value of the adenosine deaminase (ADA) activity test for the diagnosis of HIV
      positive patients in the Kurdish population. METHODS: This descriptive analytical
      case-control study was performed on 30 healthy and 60 HIV positive subjects.
      Blood CD4+ cell count was recorded and serum total ADA, and ADA1 and ADA2
      isoenzyme activities were determined. RESULTS: Serum total ADA and ADA2 isoenzyme
      activity was significantly higher in HIV positive patients than in healthy
      subjects. CD4+ cell counts markedly decreased in all patients and showed a
      significant inverse correlation with ADA activities. Using a cut-off level of
      36.52 U/L and 30.98 U/L for serum total ADA and ADA2, respectively, sensitivity
      and specificity were 90.9% and 90.27% for total ADA and 93% and 90% for ADA2,
      respectively. CONCLUSIONS: Serum ADA was significantly increased in HIV infected
      patients. Therefore, because of its low cost and simplicity to perform, ADA
      activity might be considered a useful diagnostic tool among the other markers in
      this disease.

PMID- 24133904
TI  - Evaluation of rezasurin microtiter assay and high resolution melting curve
      analysis for detection of rifampicin and isoniazid resistance of Mycobacterium
      tuberculosis clinical isolates.
AB  - BACKGROUND: Several methods have been proposed for rapid detection of drug
      resistance of Mycobacterium tuberculosis (M. tuberculosis). High resolution
      melting (HRM) curve analysis has been developed for accurate and simultaneous
      detection of resistance of M. tuberculosis isolates to rifampicin (RIF) and
      isoniazid (INH). Other techniques include the resazurin microtiter assay (REMA)
      which is one of the new colorimetric phenotypic methods. The present study
      evaluated the HRM curve analysis and REMA assay in comparison to the proportional
      method (PM) for rapid identification of multidrug resistant (MDR) M. tuberculosis
      isolates. METHODS: Thirty M. tuberculosis clinical isolates of known resistance
      phenotypes were used. An HRM curve was generated for each isolate to scan for
      mutations in the rpoB and katG genes to detect RIF and INH resistance,
      respectively. The REMA colorimetric assay was also evaluated using the same
      isolates. The results of both techniques were compared to the gold standard
      proportional method. RESULTS: The sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV), and accuracy of the REMA assay for
      RIF and INH susceptibility testing were 100%. The HRM curve assay results for RIF
      susceptibility testing were 92.3%, 100%, 100%, 94.4%, and 96.7%, respectively,
      and for INH they were 85%, 100%, 100%, 76.9%, and 90%, respectively. CONCLUSIONS:
      REMA is a rapid non-conventional and inexpensive method and may serve as a
      replacement for the proportion method in resource limited settings, while the PPV
      and NPV of the HRM curve make this assay an ideal screening method for the TB
      laboratory.

PMID- 24133905
TI  - Cytokine promoter polymorphisms and risk of colorectal cancer.
AB  - BACKGROUND: Cytokines and chemokines are involved in cancer development and
      progression, but their role in colorectal tumorigenesis is still far from well
      defined. This study investigated the association between five cytokine promoter
      polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC)
      in a hospital-based case-control study. METHODS: A total of 377 Romanian subjects
      were included in this study: 144 patients with sporadic colorectal cancer and 233
      controls. Cytokine polymorphisms (IL-1B -31T > C, IL-4R -3223C > T, IL-8 -251T >
      A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic
      discrimination TaqMan PCR assay with specific probes. RESULTS: A significant
      association was observed for IL-10 -1082A > G polymorphism, the subjects carrying
      AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 - 0.98) when
      compared with the more frequent AA genotype. Furthermore, in a dominant model the
      carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97).
      In a stratified analysis the only association between CRC and cytokine
      polymorphisms was found for carriers of IL-10 -1082G allele and was restricted to
      poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was
      observed for the remaining polymorphisms and CRC risk. CONCLUSIONS: This study
      shows that IL-10 -1082A > G polymorphism may influence CRC risk, the carriers of
      G allele being protected against CRC in the Romanian population.

PMID- 24133906
TI  - Serum sialic acid as a marker of pancreatic cancers.
AB  - BACKGROUND: The carbohydrate alterations in sialoglycoproteins and
      sialoglycolipids cause the high serum concentration of sialic acid in many types
      of cancers. The aim of this study was to evaluate the diagnostic accuracy of
      total sialic acid (TSA), lipid-bound sialic acid (LSA), and free sialic acid
      (FSA) in patients with primary pancreatic cancers. METHODS: TSA and LSA
      concentrations in the sera of 42 patients were measured by the enzymatic and FSA
      by the thiobarbituric method. RESULTS: The mean levels of TSA, LSA, and FSA in
      the sera of patients with pancreatic cancers were significantly higher than in
      controls. Taking into consideration the size and the location of the tumors,
      regional lymph node and distant metastases, there were no differences in TSA,
      FSA, and CA 19-9 levels. However, the location of tumors in the pancreas affects
      LSA levels. The sialic acids, contrary to CA 19-9, are not useful tools in the
      differential diagnosis of tumors and non-malignant diseases of the pancreas. LSA
      has the highest sensitivity, negative predictive value, accuracy, and the ability
      to discriminate cancer patients from healthy controls. The diagnostic power of
      LSA is similar to CA 19-9. CONCLUSIONS: We suggest that LSA can be useful in the
      diagnosis and evaluation of the tumor location in patients with primary
      pancreatic cancers.

PMID- 24133907
TI  - Application and development of review criteria on Sysmex XT-2100 in Chinese at a
      large third-grade class-A hospital.
AB  - BACKGROUND: Hematology analysis is an essential component of patient assessment
      and used in screening, diagnosis, and the planning of care. The objective of the
      study was to find out the suitable hematology review criteria for large scale
      general hospitals in China via the analysis of experimental data from Sysmex XE
      2100 hematology analyzer. METHODS: A total 1486 blood samples were detected with
      the Sysmes XE-2100. Based on hematology review criteria suggested by
      international consensus group and a positive smear finding new optimal review
      rules were determined. RESULTS: With the International Article 41 Review Rules,
      the true positive ratio (TP), the false positive ratio (FP), the true negative
      ratio (TN), and the false negative ratio (FN) was 14.0% (208/1486), 31.49%
      (468/1486) 52.42% (779/1486), and 2.09% (31/1486), respectively. With the help of
      Laboman 4.2 software (the Sysmex Corporation), 19 rules for review of automated
      CBC and WBC differential were set up. With our review rules, the TP, FP, TN, and
      FN was 13.86% (206/1486), 25.17% (374/1486), 58.75% (873/1486) and 2.22%
      (33/1486), respectively. The review rules were validated, the FN was 0.96%,
      blasts and immature cells were not omitted. CONCLUSIONS: The review criteria can
      be developed in light of the rules of the International Consensus Group for
      Hematology Review, but should be improved depending on different laboratory's
      requirements.

PMID- 24133908
TI  - A new triplex real time PCR which distinguishes between MRSA, MSSA, and mecA
      coagulase negative strains by means of melting point analysis using SYTO 9.
AB  - BACKGROUND: A new screening method was developed for the detection and
      identification of methicillin resistant staphylococcus aureus (MRSA) from sterile
      sites or mixed flora samples (inguinal or nose swabs). METHODS: After rapid
      treatment of samples, the method consists of two steps, template DNA preparation
      by a simple and rapid boiling procedure and a multiplex real time PCR. The
      triplex PCR system simultaneously detects the following targets, (i) the
      integration site for the open reading frame X (orfX) of the staphylococcal
      cassette chromosome mec type I - V (SCCmec), (ii) the mecA gene which codes for
      the penicillin-binding protein PBP-2a, and (iii) an internal control (IC) which
      can be amplified with the SCCmec primer system. A new buffer system, which
      contains the fluorescent dye SYTO 9, allows a reproducible real time PCR for the
      discrimination of the above mentioned PCR products by means of a high resolution
      melting point analysis (HRM). RESULTS: This new PCR system distinguishes between
      MRSA, MSSA, and mecA positive but coagulase-negative staphylococci (CoNS)
      strains. An internal control confirms the integrity of the PCR run. The HRM shows
      three melting points specific for each amplification product. 78.75 degrees C for
      the mecA gene, 83.15 degrees C for the SCCmec/orfX fragment and 88.25 degrees C
      for the internal control. CONCLUSIONS: This new multilocus MRSA PCR system is a
      fast and inexpensive alternative to commercially available test systems and costs
      only five to six euros.

PMID- 24133909
TI  - Hypoxia inducible factor-1alpha and microvessel density as angiogenic factors in
      bilharzial and non-bilharzial bladder cancer.
AB  - BACKGROUND: Hypoxia inducible factor (HIF)-1alpha is a critical regulatory
      protein of cellular response to hypoxia and is closely related to angiogenic
      processes. Microvessel density (MVD), a measure of tumor angiogenesis has been
      shown to be predictive of progression and poor prognosis in bladder urothelial
      carcinoma. Most research has relied on measuring HIF-1alpha by
      immunohistochemistry on tissue sections and studying its prognostic value.
      However, no study has investigated HIF-1alpha expression by ELISA technique in
      association with angiogenesis in bilharzial and nonbilharzial bladder carcinoma.
      The primary objective of this pilot case control study was to measure HIF-1alpha
      level by ELISA technique in voided urine samples in a trial to find a diagnostic
      applicability in patients with bilharzial and nonbilharzial bladder carcinoma.
      Secondary objectives were assessment of MVD in relation to HIF-1alpha positivity
      as well as correlating them with clinicopathological variables to get insight in
      their potential prognostic and predictive value in bladder cancer. METHODS:
      Voided urine specimens were collected from patients with histologically confirmed
      bladder urothelial carcinoma (Group 1: n = 39), urological patients without
      urothelial carcinoma (Group 2: n = 15), and healthy volunteers (Group 3: n = 15).
      All underwent serological assessment of bilharzial antibody, quantitative
      measurement of HIF-1alpha by ELISA in urothelial cells of voided urine samples
      and urine cytology. MVD was calculated by immunohistochemical staining of
      endothelial cells with CD34 on tumor tissue paraffin sections. RESULTS: There was
      a statistically significant difference between benign and malignant groups
      regarding HIF-1alpha positivity rate (p < 0.001). Urinary HIF-1alpha best cut-off
      was determined using receiver operating characteristic curves to discriminate
      between malignant and nonmalignant groups (21.7 ng/mg protein) at 82.1%
      sensitivity and 63.3% specificity. The sensitivity of urine cytology was
      increased on combination with HIF-1alpha from 53.8% to 92.8%. In the malignant
      group, MVD revealed a high score in 70% and a low score in 30% of cases compared
      to 0% and 100%, respectively, in the benign group. The difference was highly
      significant (p < 0.001). There was no significant relationship between HIF-1alpha
      positivity rate or MVD and stage, as well as histologic grade of the tumor (p >
      0.05) denoting no prognostic significance. CONCLUSIONS: HIF-1alpha can be
      reliably and quantitatively measured in urine of bladder cancer patients,
      improving the sensitivity and specificity of urine cytology for the diagnosis of
      bladder cancer. Independent studies, however, will be required on larger cohorts
      to validate these findings.

PMID- 24133910
TI  - The levels of carbohydrate antigen 19-9 are associated with gender and age in
      Chinese population.
AB  - BACKGROUND: CA 19-9 is one of the most frequently used biomarkers for tumors.
      METHODS: We analyzed the influential factors of the Carbohydrate Antigen 19-9 (CA
      19-9) levels in Chinese general population to better interpret the results of the
      CA 19-9 screening tests. 36,924 apparently healthy individuals and 1,335 patients
      with gastrointestinal (GI) tumors were involved in this study. Serum CA 19-9
      levels were measured using a Roche Cobas E601. RESULTS: The serum CA 19-9 levels
      in apparently healthy individuals were correlated with age and gender. Its level
      was positively correlated with the age of males, while it showed a V-shape curve
      in female populations. This effect could be due to sex hormones, such as
      prolactin, which were found to have a negative effect on the level of CA 19-9 in
      the present study. CONCLUSIONS: Our data indicates that gender and age could
      affect the CA19-9 serum level. We can set up different cut-off values according
      to the patient's gender and age, which can help us to get a more individualized
      representation in different populations.

PMID- 24133912
TI  - Defective NF-kB transcription factor as the mediator of inflammatory responses: a
      study on depressed Iranian medical students.
AB  - BACKGROUND: NF-kB is a transcription factor that is a downstream target of
      several cell signaling systems including TLRs. Defective expression of the
      molecule can lead to inappropriate immune responses. Previous studies revealed
      that depression can affect immune responses, but its molecular mechanisms are yet
      to be fully understood. Thus, the main aim of this study was to identify if mRNA
      levels of NF-kB are changed in the PBMCs isolated from Iranian depressed medical
      students. METHODS: This cross-sectional study was done on 38 Iranian depressed
      medical students and 43 healthy students as a control group. The mRNA levels of
      NF-kB were assessed in parallel with beta-actin (as the housekeeping gene) using
      Real-Time PCR technique. RESULTS: Our results showed that mRNA levels of NF-kB
      were significantly decreased in isolated PBMCs from depressed patients compared
      to healthy controls. CONCLUSIONS: According to the results obtained in the
      present study, it seems that depressed patients are unable to appropriately
      express NF-kB at mRNA levels which may in turn lead to defective molecule
      expression.

PMID- 24133911
TI  - Relation of protein oxidation parameters and disease activity in patients with
      Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a chronic inflammatory vasculitis
      characterized by endothelial dysfunction, elevated reactive oxygen species (ROS),
      and neutrophil hyperfunction production including acute attacks and remission
      periods. Ischemia modified albumin (IMA), advanced oxidation protein products
      (AOPP), prooxidants-antioxidants balance (PAB), and ferric reducing antioxidant
      power (FRAP) were evaluated in regard to their role in the pathogenesis of BD as
      well as their relation to clinical presentation, uveitis attacks and remission
      periods, and healthy volunteers. METHODS: The study included 28 BD cases and 27
      healthy volunteers as the control group. Blood samples were taken twice from each
      patient; first during an attack and second about three months after an attack,
      during remission period. RESULTS: AOPP, IMA and PAB levels were significantly
      increased in active periods of patients with BD compared with healthy control and
      remission periods of patients with BD (p < 0.0001, p < 0.0001, p < 0.0001,
      respectively). FRABP levels were found to be lower in active periods of patients
      with than healthy controls and remission periods of patients with BD (p < 0.001,
      p < 0.05, respectively). The AOPP levels were negatively correlated with the
      levels of FRAB in patients (r = -0.468, p = 0.012; r = -0.394, p = 0.038,
      respectively). The PAB levels were positively correlated with the levels of CRP
      in patients (r = -0.606, p = 0.001). CONCLUSIONS: Our results show that these
      parameters play a major role in the inflammatory reactions observed in BD.
      Increased levels of IMA and PAB are likely to be a result of inflammation-induced
      oxidative stress and hence its potential significance as a new marker of
      oxidative stress in BD.

PMID- 24133913
TI  - Measurement Nt-proBNP circulating concentrations in heart failure patients with a
      new point-of-care assay.
AB  - BACKGROUND: BNP (Brain Natriuretic Peptide) and Nt-proBNP (N-terminal-pro-Brain
      Natriuretic Peptide) are valuable markers for the diagnosis and prognosis of
      heart failure (HF). The AQT90 FLEX is a newly released random access analyzer for
      point-of-care (POCT) measurement. The aim of our study was to determine Nt-pro
      BNP concentrations in HF patients with the POCT assay. METHODS: Nt-proBNP levels
      were measured in seventy seven HF patients and in thirty seven healthy
      volunteers. The results were compared with a central laboratory assay. RESULTS:
      Nt-proBNP levels measured with the AQT90 FLEX were significantly correlated with
      the comparison Nt-proBNP assay and were related to HF severity. CONCLUSIONS: Nt
      proBNP testing with the AQT 90 FLEX analyzer is comparable to the central lab
      assay and may offer the advantages of POCT testing for the diagnosis and
      prognosis of heart failure.

PMID- 24133914
TI  - HPLC determination of malondialdehyde as biomarker for oxidative stress:
      application in patients with alcohol dependence.
AB  - BACKGROUND: Chronic and excess ethanol exposure causes an increase in generation
      of free radicals which attack the polyunsaturated fatty acids in membranes to
      create lipid peroxides such as malondialdehyde (MDA) which is widely used as an
      indirect biomarker of oxidative stress. METHODS: In this study a sensitive and
      reproducible high performance liquid chromatography (HPLC) method for measurement
      of MDA was applied in a group of alcohol dependent patients who underwent
      detoxification treatment. RESULTS: Compared to the control group, mean MDA
      concentrations at baseline were significantly higher in alcohol dependent
      patients (1.28 +/- 0.58 microM vs. 0.9 +/- 0.21 microM; p < 0.02). However, MDA
      levels remained almost unchanged after three weeks of detoxification treatment
      (1.28 +/- 0.58 microM vs. 1.38 +/- 0.61 microM; p > 0.05). Among alcoholic
      patients, the MDA plasma concentration in smokers was higher than in non smokers
      both at baseline and after three weeks. CONCLUSIONS: The failure to reduce the
      levels of MDA after 3 weeks of detoxification treatment suggests that patients
      with chronic alcohol dependence have difficulty in compensating for alcohol
      induced excessive production of free radicals. Furthermore, the possibility of
      cigarette smoke affecting the MDA plasma concentration cannot be ruled out.

PMID- 24133915
TI  - Effect of concomitant oral chronic dipyridamole therapy on inflammatory cytokines
      in heart failure patients.
AB  - BACKGROUND: To assess whether dipyridamole therapy exerts a significant anti
      inflammatory effect in heart failure patients. METHODS: We performed a
      retrospective analysis of the stored bio-samples of 3 groups of patients: 1) 25
      normal healthy controls (N); 2) 25 heart failure patients (HF) under standard
      optimal therapy, including aspirin; 3) 17 HF patients with previous stroke and
      under clinically-driven therapy with A (Aggrenox, long-acting dipyridamole 200 mg
      + aspirin 25 mg, twice daily) for at least 1 month (HF-A). In all, we evaluated
      interleukin (IL)-6, adiponectin and C-reactive protein (CRP) as well as NT
      proBNP. The same laboratory measurements were performed in the 17 HF patients
      with recent or previous stroke, both before and 1-month after clinically driven
      administration of A. RESULTS: All laboratory inflammatory indices were
      significantly higher in HF patients compared to N: IL-6 (N = 0.68 (0.3 - 12.7)
      vs. HF = 3.10 (0.5 - 16.7) vs. HF-A = 1.24 (0.3 - 3.3) pg/mL; p < 0.001 N vs. HF,
      p < 0.01 N vs. HF-A, p = ns HF vs. HF-A); CRP (N = 0.12 (0.01 - 0.45) vs. HF =
      0.58 (0.04 - 2.7) vs. HF-A = 0.72 (0.02 - 4.8) mg/dL; p = ns N vs. HF, p = 0.05 N
      vs. HF-A, p = ns HF vs. HF-A); Adiponectin (N = 8.8 (3.0 - 31.4) vs. HF = 12.16
      (4.9 - 27.3) vs. HF-A = 10.0 (4.8 - 15.6) pg/mL; p < 0.05 N vs. HF, p = ns N vs.
      HF-A p = ns HF vs. HF-A). NT-proBNP was also increased (N = 42.2 (13 - 93) vs. HF
      = 1907 (18.1 - 8038) vs. HF-A = 497.9 (7.8 - 3686) pg/mL; p < 0.001 N vs. HF, p =
      0.01 N vs. HF-A, p = ns HF vs. HF-A). In 17 subjects, the intra-patient
      assessment (before and 1-month after starting of Aggrenox therapy) did not show a
      decrease in inflammation markers. CONCLUSIONS: HF patients show an increase in
      inflammatory indices independently of underlying A therapy.

PMID- 24133916
TI  - Cell cycle specificity of spermatogenic cell apoptosis in rats with experimental
      varicocele.
AB  - BACKGROUND: Varicocele has been implicated as a factor responsible for
      infertility. Many researchers have shown that varicocele causes spermatogenic
      dysfunction and abnormal germ cell apoptosis. However, the effects of varicocele
      on the cell cycle and the mechanism of germ cell apoptosis have not been fully
      defined. Spermatogenic dysfunction in varicocele testes may be related partly to
      abnormal apoptosis. METHODS: Methods Forty Sprague-Dawley male rats were randomly
      divided into two groups: sham-operated group (SOG) and experimental left
      varicocele (ELV) group. Experimental varicocele was induced by partial ligation
      of the left renal vein in rats. After 90 days, two flow cytometric methods, PI
      staining and annexin V/PI labeling assays, were used to analyze the cell cycle
      and cell cycle specificity of spermatogenic cell apoptosis. RESULTS: The weight
      of the left testicle in SOG and ELV was 1.527 +/- 0.071 g and 1.223 +/- 0.136 g,
      respectively, indicating a lower left testicle weight in ELV than in SOG (p <
      0.05). Many changes were observed in ELV. Seminiferous tubules shrunk,
      spermatogenic epithelium became thinner and many spermatogenic cells dropped into
      the tubules. Furthermore, we found that the cell cycle was arrested at the phase
      of spermatogonium. Compared with SOG, the proportion of cells in G0/G1 phase
      increased from 60.632 +/- 5.144% to 74.128 +/- 17.067% (p < 0.05), and the
      proportion of cells in S phase decreased from 13.853 +/- 2.796% to 7.905 +/-
      5.314% in ELV (p < 0.05). Compared with SOG, the apoptosis index (A) increased
      from 4.345 +/- 0.554% to 14.583 +/- 3% (p < 0.05) in ELV. In ELV, apoptotic cells
      were mainly in G0/G1 and G2/M phases, and A1 (A1: Apoptosis index of G0/G1 phase)
      and A3 (Apoptosis index of G2/M phase) increased to 8.343 +/- 1.605% and 5.648 +/
      1.685%, respectively (p < 0.05). CONCLUSIONS: Spermatogenesis is arrested in
      G0/G1 phase in experimental left varicocele. The apoptosis of spermatogenic cells
      by a varicocele may be induced in G0/G1 and G2/M phases of the cell cycle.
      Apoptosis of germ cells with DNA damage may be the principal method through which
      the testis eliminates arrested germ cells.

PMID- 24133917
TI  - Association of iron overload and oxidative stress with insulin resistance in
      transfusion-dependent beta-thalassemia major and beta-thalassemia/HbE patients.
AB  - BACKGROUND: Beta-thalassemia causes a severe hemolytic anemia in patients
      necessitating frequent transfusions leading to iron overload and endocrine
      complications, especially diabetes mellitus. We tried to determine the change or
      effect on carbohydrate physiology and oxidation markers and the association of
      these markers in chronic transfusion-dependent beta-thalassemia major and beta
      thalassemia/HbE (beta-TM) patients. METHODS: Prospective study on 60 beta-TM
      patients, receiving only regular blood transfusions, and 20 healthy controls were
      enrolled for oral glucose tolerance test, fasting insulin, Homeostasis Model
      Assessment of insulin resistance (HOMA-IR), liver function test, iron overload,
      oxidative stress, and lipid profile at baseline. The same tests were repeated
      after 6 months. RESULTS: One beta-TM patient had impaired glucose tolerance.
      Fasting glucose, insulin, ferritin, MDA, TG concentrations, HOMA-IR, and liver
      profiles were significantly higher while Hb, Hct, TC, HDL-C, LDL-C concentrations
      and TAC were significantly lower in beta-TM patients than controls (p < 0.001).
      Fasting glucose, HOMA-IR and beta-cell function were significantly correlated
      with MDA and glucose, AST, ALT, MDA were significantly correlated with ferritin
      (p < 0.05). Multiple forward stepwise linear regression analyses of the
      significant variables showed that in these beta-TM patients, independent
      predictors of HOMA-IR were fasting glucose (beta = 0.634, r2 = 0.374, p < 0.001),
      HDL-C (beta = 0.249, r2 = 0.418, p = 0.043) and MDA (beta = 0.225, r2 = 0.466, p
      = 0.029). CONCLUSIONS: Progression of iron overload, oxidative stress and
      hyperinsulinemia were substantially and persistently higher in beta-TM patients.
      We observed a positive association between oxidative stress, iron overload and
      insulin resistance in these beta-TM patients.

PMID- 24133919
TI  - Experience with an alternative form of samples for external quality assessment of
      urinary sediment (visual sample EQA).
AB  - BACKGROUND: Urinary sediment components are mainly unstable, especially in their
      original forms. This makes the use of such material in routine external quality
      assessment surveys (EQAS) almost impossible. The development of an alternative
      EQAS for urinary sediment using photomicrographs (visual-sample EQAS) is
      described here, together with results, improvements and future plans. METHODS:
      The original survey allowed a free-text interpretation, which proved to be time
      consuming and impractical. The next phase included a multiple choice answer (one
      from five alternatives). The current version challenges the participant with a
      list of over 50 alternatives, together with a "not-in-the-list" possibility.
      RESULTS: Certain elements are always interpreted more correctly (examples:
      erythrocytes, squamous cells, renal epithelial cells, bacteria--above 90%) than
      others (examples: leukocytes, fat droplets, certain crystals--below 55%).
      Pictures are included which are atypical (for example: decoy cells, which must be
      interpreted correctly, other artefacts). Occasionally interesting structures are
      included, but which are not evaluated. CONCLUSIONS: The two-dimensional pictures
      often limited the interpretation possibilities, so that in such cases more than
      one answer was allowed. The possibility of "online microscopy" using staple
      pictures is at present in evaluation. The acceptance of this type of EQAS is seen
      by the number of participants, at present over 500 per survey, four surveys per
      year.

PMID- 24133918
TI  - Establishment of tacrolimus-induced diabetes in rat model and assessment of
      clinical treatments for post-transplant diabetes mellitus in liver transplant
      recipients.
AB  - BACKGROUND: To establish a tacrolimus-induced diabetes rat model and assess
      efficacy and safety of insulin glargine combined with repaglinide in Chinese
      patients with diabetes after liver transplantation. METHODS: Animal experiments
      and clinical trial were conducted. Animal experiments: Male SD rats were randomly
      divided into tacrolimus (4 mg/kg daily) and control group (saline). Rats were
      sacrificed after five months of treatment and blood was collected through heart
      puncture. Patients who underwent liver transplantation were selected and followed
      up regularly. If HbA1c was < 9%, repaglinide was administered; if HbA1c was > or
      = 9%, glargine plus repaglinide was administered. RESULTS: For rat model studies,
      in the tacrolimus group, fasting blood glucose (FBG) levels were increased after
      three months (p < 0.01). After five months, the insulin secretion index and the
      sensitivity index in the tacrolimus group was significantly lower than in the
      control group (p < 0.01). For studies of post-transplant diabetes mellitus
      (PTDM), eighty-six liver transplant recipients were enrolled. 51 were given
      repaglinide and 35 were given repaglinide combined with glargine. After treatment
      for 1, 6, and 12 months, FBG, post-prandial blood glucose (PPBG), and HbA1c
      levels decreased (p < 0.05) in both groups, and no statistically significant
      changes were observed in the liver and kidney function indicators (p > 0.05). No
      severe hypoglycemia episodes were reported. CONCLUSIONS: Tacrolimus caused islet
      cell necrosis, reduced insulin secretion, increased insulin resistance, and
      increased blood glucose in the model. The blood glucose levels increased in a
      time-dependent manner. Combination of glargine and repaglinide was effective and
      safe for Chinese patients with post liver transplant diabetes mellitus.

PMID- 24133920
TI  - Comparison of automated methods for measurement of 25-hydroxyvitamin D.
AB  - BACKGROUND: The objective of the study was to compare the analytical performance
      of three automated immunoassays for the determination of serum 25-hydroxyvitamin
      D. METHODS: Quantitative determination of serum 25(OH)D were performed by
      "Vitamin D total" (n = 131) and "Vitamin D3(25-OH)" (n = 77) assays (Roche
      Diagnostics) on a Cobas e411 and by "25-OH Vitamin D" (n = 131) assay (Abbott
      Laboratories) on an Architect. The inter-assay precision was calculated and
      methods were compared by the Passing Bablok regression and Bland-Altman analysis.
      RESULTS: The "Vitamin D total" demonstrated stronger correlation (r = 0.863) and
      better agreement (bias = -7.89 nmol/L) with the "25-OH Vitamin D" than with the
      "Vitamin D3(25-OH)" (r = 0.716; bias = +18.6 nmol/L). The inter-assay precision
      (% CV) for the "Vitamin D total" and "25-OH Vitamin D" assays, were respectively
      3.47 to 6.14 and 4.27 to 8.56. CONCLUSIONS: The results of this study demonstrate
      that Abbott "25-OH Vitamin D" and Roche "Vitamin D total" are rapid and precise
      methods for 25(OH)D serum measurement over a wide reportable range on automated
      immunoassay platforms. The Abbott assay exhibited better correlation and
      agreement with the new Roche assay than the "Vitamin D3(25-OH)" Roche assay.
      Between method differences observed in this study still indicates the need for
      standardization of 25(OH)D assays.

PMID- 24133921
TI  - The diagnostic efficacy of urinary survivin and hyaluronidase mRNA as urine
      markers in patients with bladder cancer.
AB  - BACKGROUND: A new, sensitive, noninvasive method for the detection of urothelial
      carcinomas of the bladder would open new possibilities in both the diagnosis and
      follow up of patients. METHODS: Voided urine specimens were collected from
      patients with histologically confirmed bladder urothelial carcinoma (Group 1: n =
      60), urological patients without urothelial carcinoma (Group 2: n = 20), and
      healthy volunteers (Group 3: n = 20). All underwent serological assessment of
      schistosomiasis antibody, quantitative measurement of survivin by ELISA in urine
      supernatant, urine cytology, and detection of hyaluronidase (HYAL-1) by RT-PCR in
      urothelial cells of voided urine samples. RESULTS: Urinary survivin mean rank was
      higher in malignant and benign groups than in the healthy group (p < 0.001).
      Urinary survivin best-cutoff was determined using receiver operating
      characteristic curve to discriminate between malignant and nonmalignant groups
      (2537.25 pg/mg protein) at 78.33% sensitivity and 82.5% specificity. HAase mRNA
      showed superior sensitivity (86.67%) over cytology (38.33%) and urinary survivin
      (78.33%) with specificity of 97.5%, 100%, and 82.5%, respectively. The
      sensitivity of urine cytology was increased on combination with either survivin
      (83.33%) or HAase (90%). Also, the combination of both markers increased overall
      sensitivity (95%). CONCLUSIONS: Survivin can be reliably and quantitatively
      measured in urine of bladder cancer patients, improving the sensitivity and
      specificity of urine cytology for the diagnosis of bladder cancer. Combined use
      of cytology with survivin and HAase was the best recommended combination for
      bladder cancer detection.

PMID- 24133922
TI  - Acute myocardial infarction in an 8-year old male child with homozygous familiar
      hypercholesterolemia: laboratory findings and response to lipid-lowering drugs.
AB  - BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited
      metabolic disease, caused by low-density lipoprotein (LDL) receptor abnormality,
      consequently leading to an increase of serum levels of LDL cholesterol (LDL-C).
      Clinically, this disease is characterized by the deposition of LDL-C in skin,
      tendons, and arterial wall. Children with HoFH develop significant coronary
      artery disease (CAD) in the first decade of life and frequently die of myocardial
      infarction (MI) before 20 years of age. METHODS: An 8-year-old boy with a
      diagnosis of acute MI on January 15, 2012 was admitted to our hospital for
      further evaluation of the potential cause and treatment. He had severe
      hypercholesterolemia for the past several years and showed typical signs of FH.
      Laboratory work-up excluded secondary causes of hypercholesterolemia and a
      diagnosis of HoFH was made after assessing the lipid profiles of his parents and
      his relatives. After careful consideration, he was prescribed a combination
      regime of lipid-lowering therapy. The plasma pro-protein convertase
      subtilisin/kexin type 9 (PCSK9) levels were also evaluated for him and his family
      members. RESULTS: His total cholesterol (TC) was 18.96 mmol/L and both parents
      had hypercholesterolemia (TC of mother: 7.46 mmol/L and father: 8.74 mmol/L). The
      plasma level of PCSK9 of the patient was significantly higher than his parents
      and his uncles and this pattern was similar with the level of their lipid
      profile. Importantly but not surprisingly, his serum lipid profile was not
      significantly improved by concomitant use of rosuvastatin 10 mg and ezetimibe 10
      mg daily for one month, even a double dose of rosuvastatin and ezetimibe 10 mg
      daily for another month. CONCLUSIONS: The present case may have an important
      clinical implication for future investigation regarding the relation of HoFH to
      statin and PCSK9.

PMID- 24133923
TI  - Concentration of plasma neutrophil gelatinase-associated lipocalin in patients
      with chronic kidney disease.
AB  - BACKGROUND: The inclining incidence of chronic kidney disease which has led to
      high mortality and immense medical burden over the past decades has become a
      distressing concern in epidemiology. Unfortunately, the number of biomarkers that
      allow the monitoring of chronic kidney disease (CKD) is limited. Neutrophil
      gelatinase-associated lipocalin (NGAL) is an emerging biomarker which has been
      shown to be able to diagnose kidney injuries. METHODS: Eighty-one nondiabetic
      patients with chronic kidney disease, stage 2 to 5, were recruited for this
      study, and 17 healthy volunteers with eGFR greater than 90 mL/minute/1.73m(2)
      were selected as the control group. RESULTS: Our study demonstrated that the
      pNGAL level is elevated during CKD, and the pNGL level has a strong correlation
      with the concentration of sCr and eGFR. CONCLUSIONS: Plasma neutrophil gelatinase
      associated lipocalin is a potent tool in the diagnosis of chronic kidney diseases
      and is shown to have high correlation with serum creatinine and estimated
      glomerular filtration rate.

PMID- 24133924
TI  - Frequency of human enterovirus 71 in children under 8 years old with aseptic
      menengitis in Tehran.
AB  - BACKGROUND: Human enterovirus 71 (HEV71) was isolated for the first time from an
      infant with encephalitis in California in 1969 and then spread through the world.
      It has emerged as a major cause of a vast variety of diseases such as epidemics
      of hand, foot and mouth disease (HFMD), aseptic meningitis (AM), acute flaccid
      paralysis, and encephalitis. The aim of this study was to determine the
      prevalence of enterovirus 71 in children < 8 years old who were hospitalized due
      to primary diagnosis of AM in Tehran. METHODS: One hundred cerebrospinal fluid
      samples (CSF) were collected by physicians from children with a diagnosis of AM
      and transported on ice to the Pasteur Institute of Iran for further processing.
      Viral RNA was extracted and EV71 infection was detected by RT-PCR method using
      the specific primers. RESULTS: EV71 infection was detected in 14 patients (14%).
      Eight (57.14%) patients were younger than 2 years old, 11 (78.57%) were male and
      3 (21.43%) were female. The seasonal peaks of EV71 were observed during autumn
      and winter with 6 (42.86%) and 5 (35.71%) cases, respectively. CONCLUSIONS: EV71
      should be considered as a causative agent of AM in Iran with the epidemiological
      pattern similar to that of other enteroviruses as males are more susceptible to
      be affected by these viruses. Further studies on this virus are needed to improve
      our knowledge about them in our country.

PMID- 24133925
TI  - Evaluation of three APTT reagents in a routine laboratory: toward a compromise.
AB  - BACKGROUND: Our current activated partial thromboplastin time (APTT) reagent (PTT
      A) is often prolonged for unexplained reasons. METHODS: We decided to compare
      this reagent with an alternative reagent (Cephascreen) and with our second line
      APTT (Actin FS) in terms of cut-off values, sensitivity to in-vitro coagulation
      factor deficiencies, sensitivity to lupus anticoagulant (LA), and in vivo
      sensitivity to unfractionated heparin (UFH). RESULTS: Actin FS, PTT-A, and
      Cephascreen were prolonged for FVIII level at 60%, 40%, and 40% respectively, FIX
      at 50%, 25%, and 35%, and FXI at 60%, 20%, and 50%. PTT-A showed the same
      sensitivity and specificity as Cephascreen to LA. Actin FS and PTT-A appeared
      less suitable to monitor UFH regarding the CLSI criteria. CONCLUSIONS:
      Cephascreen fulfilled the CLSI performance criteria, with a good compromise in
      terms of sensitivity to factor deficiency and with a substantial reduction of
      complementary analysis in our routine practice.

PMID- 24133926
TI  - A novel PCBD gene mutation in an Iranian patient with hyperphenylalaninemia.
AB  - BACKGROUND: Neonatal screening for PKU is carried out nationally and our center
      is one of the referral centers for molecular analysis of PKU in Iran.
      Hyperphenylalaninemias are common disorders of phenyalanine catabolism. Six
      genes, including PAH, PTPS, DHPR, GTPCH, SR, and PCBD, independently play a role
      in this disorder. METHODS: A 2-year-old boy was referred to our center for
      genetic diagnosis of PKU. PAH gene was sequenced but no mutation was found. Using
      the STR based linkage mapping approach, BH4-metabolizing genes were screened.
      RESULT: A pattern of autozygosity by descent (ABD) suggested that the PCBD gene
      may be involved in this family. The PCBD gene was sequenced and a homozygous T >
      C substitution (X105Q) was found in the termination codon. CONCLUSIONS: Although
      most of the reported mutations in PCBD gene are single substitutions or premature
      stop codons causing a benign or transient form of BH4 deficiency, this novel
      mutation was found in the stop codon.

PMID- 24133927
TI  - Rapid detection of respiratory syncytial virus (RSV) in children with acute lower
      respiratory tract infections: a pilot evaluation of an immuno-chromatographic
      rapid antigen detection method.

PMID- 24133928
TI  - Killing machines.

PMID- 24133930
TI  - Provision of antiretroviral care to displaced populations in humanitarian
      settings: a systematic review.
AB  - Providing antiretroviral treatment (ART) in humanitarian settings is challenging.
      Reports suggest that ART provision is feasible, but the evidence base is scarce.
      We systematically searched three databases for studies reporting ART outcomes
      among displaced populations in settings of conflict, natural disasters or
      political instability, and estimated overall mortality using random effects
      models. Fourteen studies were identified, six in conflict areas, five in areas of
      post-election violence and three in natural disaster settings. The pooled
      proportion for mortality was 7.6% (95% CI 5.3-10.0%) at six months and 9.0% (95%
      CI 5.8-12.2%) at 12 months. Loss-to-follow-up at six months was 6.3% (95% CI 4.3
      8.3%) and at 12 months was 8.1% (4.9-11.2%). Adherence was comparable to stable
      settings. Strategies used to support ART provision included additional drug
      stocks and establishing peer communication networks. Good clinical outcomes can
      be achieved with ART in disaster setting, in particular if supported by regional
      collaboration, standardized drug regimens and contingency planning.

PMID- 24133929
TI  - Political violence, collective functioning and health: a review of the
      literature.
AB  - Political violence is implicated in a range of mental health outcomes, including
      PTSD, depression, and anxiety. The social and political contexts of people's
      lives, however, offer considerable protection from the mental health effects of
      political violence. In spite of the importance of people's social and political
      environments for health, there is limited scholarship on how political violence
      compromises necessary social and political systems and inhibits individuals from
      participating in social and political life. Drawing on literature from multiple
      disciplines, including public health, anthropology, and psychology, this
      narrative review uses a multi-level, social ecological framework to enhance
      current knowledge about the ways that political violence affects health. Findings
      from over 50 studies were analysed and used to build a conceptual model
      demonstrating how political violence threatens three inter-related domains of
      functioning: individual functioning in relationship to their environment;
      community functioning and social fabric; and governmental functioning and
      delivery of services to populations. Results illustrate the need for multilevel
      frameworks that move beyond individual pathology towards more nuanced
      conceptualizations about how political violence affects health; findings
      contribute to the development of prevention programmes addressing political
      violence.

PMID- 24133931
TI  - Medical care as the carrot: the Red Cross in Indonesia during the war of
      decolonization, 1945-1950.
AB  - During the war of decolonisation in Indonesia 1945-1950, the Dutch Red Cross and
      the Dutch East Indies Red Cross delivered aid to sick and wounded soldiers and
      civilians. This was supposed to happen in cooperation with organisations
      including the Indonesian Red Cross, the International Committee of the Red Cross,
      the military health service and civilian health services. Due to lack of
      resources, doctors and nurses, and due to differing interests, cooperation went
      anything but smoothly, severely undermining medical aid. On top of that, the aid
      that was given turned out be a tool of propaganda for the Dutch cause. Aid was
      deliberately--and with Red Cross consent--used as a political-military tool in
      the service of Dutch national interests. In a military strategy of carrot and
      stick, medical care served as the carrot.

PMID- 24133932
TI  - Injured and disabled casualties of the Northern Ireland conflict: issues in
      immediate and long-term treatment, care and support.
AB  - Even though injury due to armed conflict is more commonly caused than death,
      research into injury due to Northern Ireland's four decades of otherwise
      exhaustively documented conflict is sparse. This article reports on a 2011 study
      based on interviews with 30 people seriously physically injured in the conflict
      and 20 of their carers and a self-administered questionnaire survey of a further
      90 people injured in political violence in Northern Ireland. All injured
      respondents reported that emergency medical emergency treatment had been
      excellent. Those injured in the 1970s reported low expectations of their life
      expectancy and rehabilitation, a lack of psychological support and lack of help
      with chronic injury-related conditions. More recently injured people had
      psychological support and were more successfully rehabilitated but those injured
      earlier often saw it as 'too late' for psychological help. Influences on well
      being seem to be: changing professional standards and awareness; policies
      acknowledging of the effects of conflict; anti-discrimination legislation;
      development of rehabilitation services; and the reform of disability benefits.
      Inter alia, health professionals' attitudes towards victims and their treatment
      of injury appear to have a significant influence on outcomes for injured people.

PMID- 24133933
TI  - Facing the new term head on.

PMID- 24133934
TI  - Plain tobacco packs up urgency to kick the habit.

PMID- 24133935
TI  - The power of information: from policy to implementation.

PMID- 24133936
TI  - Re: Uniforms.

PMID- 24133937
TI  - Student voices are heard at the CPHVA Question Time event.

PMID- 24133938
TI  - School nurse 121 campaign.

PMID- 24133939
TI  - Breaking barriers.

PMID- 24133940
TI  - Laugh with Mary.

PMID- 24133941
TI  - Assisting healthcare professionals in understanding drivers and barriers to
      improving pre-school immunisation uptake.
AB  - Improving the uptake of immunisations in preschool children is an ongoing public
      health policy strategy. Delineating the drivers and barriers affecting uptake may
      be helpful to health care professionals aiming to assess their own effectiveness
      or understand confounding factors when implementing improvement initiatives.
      Relevant literature was collated and placed into one of three over arching
      domains i) Wider environment ii) Home environment and iii) Practice Factors. A
      range of sub-domains are presented in addition to metrics to enable their
      assessment. The list of domains will be helpful to health care professionals
      interested in developing quality improvement programmes to increase or assess pre
      school immunisation uptake.

PMID- 24133942
TI  - Assessing and responding to infant mental health needs.
AB  - Early recognition of mental health problems in maltreated infants, coupled with
      tailored support to aid recovery, has the potential to offer significant benefits
      to a population whose needs have perhaps remained hidden in the past. All forms
      of maltreatment may adversely affect infant mental health, but perhaps none more
      so than emotional neglect. Universal contact with families with young children
      makes health visitors ideally placed to provide early support to this vulnerable
      group, but such practice requires considerable knowledge and understanding. This
      paper examines how emotional neglect can impact on an infant's mental health and
      explores how health visitors can assess and respond effectively to this key
      health need. Throughout, the term 'infant' is used to describe children from
      birth to age three.

PMID- 24133943
TI  - A survey of antenatal advice and education by the Sedgemoor Health Visitor Team.
AB  - The Healthy Child Programme includes an antenatal contact with the health visitor
      between 28 and 36 weeks gestation. In South Sedgemoor, health visitors had
      previously run an antenatal parenting session as part of the parentcraft
      education provided by the midwives. This had stopped due to a number of reasons.
      The decision was made to survey expectant parents to determine their views on how
      best this antenatal contact with the health visitor could be achieved. Sixty-six
      questionnaires were handed out and 73% responded. It was evident from the
      findings that the vast majority of parents questioned (82%) wanted individual
      face-to-face to contact with health visitors and midwives, with only 27% wanting
      to attend a small group. There was a clear request that this contact was to be
      done in the surgery (59%), although 36% felt that home or the children's centre
      would be an appropriate place. The parents mostly felt that the best time for
      this to happen would be during the day (48%) or at the weekend (30%). This small
      survey shows how important it is for individual health visiting teams to identify
      the antenatal needs of their clients in each locality and to listen to what they
      want.

PMID- 24133944
TI  - NICE guidance points the way to tackling eczema in children.
AB  - By prioritising time for assessment and including practical demonstrations on how
      much of the treatments to use, how often to apply treatments, when and how to
      step treatment up or down, and how to treat infected atopic eczema, the guideline
      sets an invaluable precedent on the role that healthcare professionals should
      play in improving patient care. The earlier a child's eczema gets successfully
      treated the better chance that long-term damage to the skin is avoided--good news
      for the child, the carer and healthcare professionals.

PMID- 24133945
TI  - Setting up a health visitor advice line: the truth behind the call.

PMID- 24133946
TI  - Clinical update: vomiting in infants.
AB  - Vomiting is very common in infants and is mostly caused by non-serious
      conditions. However, community practitioners may come across infants with serious
      causes of vomiting, requiring prompt referral. Bilious vomiting should always
      raise suspicion of a surgical cause and needs urgent assessment by the
      paediatric/surgical team. The role of community practitioners in the assessment
      of vomiting infants for 'red flag' symptoms and early interventions are
      discussed.

PMID- 24133947
TI  - 'Seek the possible'.

PMID- 24133948
TI  - The South African obsession--and shame.

PMID- 24133949
TI  - The authors respond.

PMID- 24133950
TI  - Biological aspects of periodontal tissue regeneration: cementogenesis and the
      induction of Sharpey's fibres.
AB  - The realm of periodontal tissue regeneration has a plethora of unanswered
      questions and challenges due to the complexity of restoring mineralised and
      fibrous connective tissues ultimately to be covered by epithelium in a very
      specific spatial organisation. Wound healing of the periodontium follows a highly
      ordered sequence of events that guides cellular morphology, differentiation,
      migration and proliferation and comprises a series of cellular, extracellular and
      molecular reciprocal interactions. The prerequisite for regeneration of any
      structure is the trio of a soluble molecular signal, a scaffold and responding
      stem cells. Striated muscle represents an abundant source of easily accessible
      tissue that contains several perivascular, pericytic and myoblastic cell niches
      capable of differentiating and inducing selected tissue phenotypes and
      morphogenesis. Morcellated autogenous rectus abdominis muscle combined with 75
      microg of hTGF-beta3 in Matrigel matrix implanted into non-human primate class II
      and III furcation defects induced greater alveolar bone formation and
      cementogenesis when compared to furcation defects without the addition of
      morcellated autogenous bone. In situ hybr disation and immunohistochemistry
      during embryonic development and tooth morphogenesis have shown synchronous but
      spatially different bone morphogenetic proteins (BMPs) expression during tissue
      induction and morphogenesis. Preclin cal studies in the non-human primate Papio
      ursinus have shown a seemingly specific cementogenic function of osteogenic
      protein-1 (OP-1, also known as BMP-7) when treating Class II furcation defects of
      Papio ursinus. In context, hOP-1 is preferentially cementogenic when implanted
      into non-human primate class II and III furcation defects whilst hBMP-2 is highly
      osteogenic but not cementogenic when in contact with dentine extracellular
      matrix. Importantly, naturally-derived highly purified BMPs/OPs, recombinant hOP
      1 and hTGF-beta3 when implanted into non-human primates Class II and III
      furcation defects induce cementogenesis with morphologically and functionally
      oriented periodontal ligament fibres coursing within a newly formed highly
      vascular periodontal ligament space with Sharpey's fibres generated within the
      newly secreted cementoid matrix. The grand challenge of molecular and therapeutic
      implications is the biological significance of apparent redundancy. The presence
      of several homologous but molecularly different isoforms all endowed with the
      striking capacity of inducing "bone formation by autoinduction" indicates that
      there is a structure/activity profile amongst soluble osteogenic molecular
      signals; this suggests a therapeutic significance in clinical contexts. The
      structure/activity profile finely tunes the vast pleiotropic activities of the
      soluble molecular signals in mineralised and non-mineralised tissues profoundly
      modulating epithelial/mesenchymal tissue interactions. Significant advances in
      regenerative tissue engineering may be expected if ongoing research is tailored
      to provide further mechanistic and morphological insights into the relevance of
      the apparent redundancy and the structure/activity profile of the recombinant
      human osteogenic proteins. The presence of the structure/activity profile
      together with the biological significance of apparent redundancy will necessitate
      re-shaping and re-engineering developing newly devised targeted therapeutics for
      periodontal tissue engineering.

PMID- 24133952
TI  - Oral medicine case book 52: pleomorphic adenoma of the upper lip.

PMID- 24133951
TI  - The importance of glide path preparation in endodontics: a consideration of
      instruments and literature.
AB  - The efficacy of root canal preparation is considerably enhanced when an effort is
      made to provide an effective glide path. In addition the risk of undesirable
      fractures of instruments is reduced. The introduction of techniques and in
      struments specifically directed at the preparation of a glide path have
      facilitated root canal shaping and provide a variety from which the clinician may
      choose, guided by the relevant design features and performance characteristics.

PMID- 24133953
TI  - Maxillo-facial radiology case 113. Osteochondroma.

PMID- 24133954
TI  - Warnings--written is always best.

PMID- 24133955
TI  - The view from the edge: rethinking a few ideas.

PMID- 24133956
TI  - Grammar structures and deaf and hard of hearing students: a review of past
      performance and a report of new findings.
AB  - Results of a study are presented that suggest the grammatical structures of
      English some deaf and hard of hearing students struggle to acquire. A review of
      the literature from the past 40 years is presented, exploring particular lexical
      and morphosyntactic areas in which deaf and hard of hearing children have
      traditionally exhibited difficulty. Twenty-six participants from an urban day
      school for the deaf used the LanguageLinks software, produced by Laureate
      Learning Systems, for 10 minutes daily for 9 weeks. The descriptive analysis of
      the results expands on findings reported by Cannon, Easterbrooks, Gagne, and Beal
      Alvarez (2011). The results indicated that many participants struggled with
      regular noun singular/plural; accusative first- and second-person singular;
      noun/verb agreement copular "be"; accusative third-person number/ gender;
      locative pronominals; auxiliary "be"/regular past "-ed;" and prenominal
      determiners plural.

PMID- 24133957
TI  - Increasing children's ASL classifier production: a multicomponent intervention.
AB  - The Authors examined classifier production during narrative retells by 10 deaf
      and hard of hearing students in grades 2-4 at a day school for the deaf following
      a 6-week intervention of repeated viewings of stories in American Sign Language
      (ASL) paired with scripted teacher mediation. Classifier production, documented
      through a multiple-baseline-across-participants design, was followed by visual
      analysis and calculation of the percentage of non-overlapping data (Scruggs,
      Mastropieri, & Casto, 1987). Following the intervention, most students increased
      specific elements within their classifier production during narrative retells of
      stories they had watched and showed improved performance from pre- to
      postintervention measures. Picture support and fading of teacher mediation during
      retells variably affected classifier production. The results suggest that
      students may benefit from tailored intervention, including repeated viewings of
      ASL models paired with teacher mediation and possibly picture support, to
      increase classifier production during narrative retells.

PMID- 24133958
TI  - Deaf and hard of hearing students' perspectives on bullying and school climate.
AB  - Student perspectives reflect school climate. The study examined perspectives
      among deaf and hard of hearing students in residential and large day schools
      regarding bullying, and compared these perspectives with those of a national
      database of hearing students. The participants were 812 deaf and hard of hearing
      students in 11 U.S. schools. Data were derived from the Olweus Bullying
      Questionnaire (Olweus, 2007b), a standardized self-reported survey with multiple
      choice questions focusing on different aspects of bullying problems. Significant
      bullying problems were found in deaf school programs. It appears that deaf and
      hard of hearing students experience bullying at rates 2-3 times higher than those
      reported by hearing students. Deaf and hard of hearing students reported that
      school personnel intervened less often when bullying occurred than was reported
      in the hearing sample. Results indicate the need for school climate improvement
      for all students, regardless of hearing status.

PMID- 24133959
TI  - Deaf students' knowledge of subtle lexical properties of transitive and
      intransitive English verbs.
AB  - Deaf learners' acquisition of fundamental lexical properties of high-frequency
      English verbs related to transitivity and intransitivity was examined, including
      the subtle distinction between unergative and unaccusative verbs. A 140-item
      sentence acceptability rating scale was used to assess this lexical knowledge in
      deaf college students at two English proficiency levels, plus a control group of
      hearing native English speakers. Hypotheses addressed the influence of relative
      derivational complexity and overall English proficiency on verb acquisition.
      Though the hearing group showed greater accuracy in sentence acceptability
      judgments and greater accuracy tied to overall English proficiency, the two deaf
      groups displayed fairly robust knowledge of targeted verbs' fundamental
      transitive and intransitive lexical properties. Nevertheless, verb acquisition
      remains a formidable challenge. Further research should assess deaf students'
      knowledge of these lexical properties in lower-frequency English verbs, including
      unaccusative verbs prevalent in STEM (science, technology, engineering,
      mathematics) and other academic discourse.

PMID- 24133960
TI  - Assessment accommodations on tests of academic achievement for students who are
      deaf or hard of hearing: a qualitative meta-analysis of the research literature.
AB  - The authors conducted a qualitative meta-analysis of the research on assessment
      accommodations for students who are deaf or hard of hearing. There were 16
      identified studies that analyzed the impact of factors related to student
      performance on academic assessments across different educational settings,
      content areas, and types of assessment accommodations. The meta-analysis found
      that the results of analyses of group effects of accommodated versus
      unaccommodated test formats are often not significant, test-level factors exist
      that can affect how students perceive the assessments, and differences exist in
      how test items function across different conditions. Student-level factors,
      including educational context and academic proficiency, influence accommodations'
      role in assessment processes. The results of this analysis highlight the
      complexity of and intersections between student-level factors, test-level
      factors, and larger policy contexts. Findings are discussed within the context of
      larger changes in academic assessment, including computer-based administration
      and high-stakes testing.

PMID- 24133961
TI  - Promoting self-determination of students who are deaf or hard of hearing.
AB  - Self-determination is a combination of attitudes, knowledge, and skills that
      enables individuals to make choices and engage in goal-directed, self-regulated
      behavior. Research in special education has demonstrated the benefits of
      promoting self-determination in achieving positive adult outcomes. However, to
      date, very little has been written about self-determination as it relates to the
      education of students who are deaf or hard of hearing. This article provides an
      overview of self-determination, suggestions for instructional planning, and
      guidance on resources that can be used to gather additional information.

PMID- 24133962
TI  - [Advance in the study of myocardial ischemic preconditioning and postconditioning
      and the clinical applications].
AB  - Myocardial ischemic preconditioning and postconditioning can reduce myocardial
      infarct size, improve myocardial contractility, protect coronary endothelial and
      myocardial cell ultrastructure, as well as reduce the incidence of arrhythmias.
      Clinical practice has confirmed the safety and efficacy of these two methods of
      myocardial protection. This paper reviewed about ischemic preconditioning and
      postconditioning protection mechanisms in myocardial ischemia reperfusion injury
      and clinical research literatures in recent years, to provide a theoretical basis
      for finding new treatment strategies on the prevention and treatment of ischemic
      cardiomyopathy.

PMID- 24133963
TI  - [Sphingosine kinase 1 and tumor].
AB  - Sphingolipids as an important regulator play a critical role in the cell
      biological functions. Among them, ceramide (Cer) and sphingosine (Sph) induce
      apoptosis and inhibit cell proliferation; on the contrary sphingosine 1-phosphate
      (S1P) promotes cell survival and proliferation. The balance between
      ceramide/sphingosine and S1P forms a so-called "sphingolipid-rheostat", which
      decides the cell fate. Sphingosine kinases, which catalyze the phosphorylation of
      sphingosine to S1P, are critical regulators of this balance. Here, we review the
      role of sphingosine kinase 1 (SphK1) in regulating fundamental biological
      processes and tumorigenesis and the potential of SphK1 as a new target for cancer
      therapeutics.

PMID- 24133964
TI  - [Progress in the study of BLyS and APRIL on regulating T cell responses in
      rheumatoid arthritis].
AB  - B lymphocyte stimulator (BLyS), a tumor neurosis factor ligand superfamily, is an
      important factor of B cell survival and activation. However, BLyS also regulates
      T cell activation and survival, playing key roles in T cell-mediated autoimmune
      disorders. In the paper, we introduced the mechanisms of BLyS and a proliferation
      inducing ligand (APRIL) regulating T cell responses and their roles in rheumatoid
      arthritis (RA).

PMID- 24133965
TI  - [Progress in anti-cancer research of American ginseng: with an example of
      colorectal cancer].
AB  - Cancer is a group of various diseases, all of which involve unregulated cell
      growth. Many currently used chemotherapeutic drugs are derived from botanicals.
      Thus, searching botanical sources for novel oncology medications, including
      identifying the lead compounds and their derivatives for chemoprevention, is an
      essential step in advancing cancer therapeutics. This article mainly focuses on
      the data from our previous American ginseng anti-colon cancer studies. In
      addition to the potential role of American ginseng on cancer, the herb as an
      adjuvant for cancer treatment is presented, including describing the attenuation
      of adverse events induced by chemotherapeutic agents and increasing of quality of
      cancer patient life. Since heat-treated American ginseng and ginsenoside gut
      microbiome metabolites showed significant increases in cancer chemopreventive
      effects, active constituents of the steamed herb and their gut metabolites should
      be clearly identified, and the structure-activity relationship should be further
      explored. Data obtained from herbal medicine studies and clinical trials will
      help develop useful anticancer agents.

PMID- 24133966
TI  - [Recent progress in development of antibiotics against Gram-negative bacteria].
AB  - Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram
      negative pathogens, have emerged to be one of the world's greatest health
      threats. However, not only have recent decades shown a steady decline in the
      number of approved antimicrobial agents but a disappointing discovery also void.
      The development of novel antibiotics to treat MDR Gram-negative bacteria has been
      stagnated over the last half century. Though few compounds have shown activities
      in vitro, in animal models or even in clinical studies, the global antibiotic
      pipeline is not encouraging. There are a plethora of unexpected challenges that
      may arise and cannot always be solved to cause promising drugs to fail. This
      review intends to summarize recent research and development activities to meet
      the inevitable challenge in restricting the proliferation of MDR Gram-negative
      bacteria, with focus on compounds that have entered into clinical development
      stage. In addition to new analogues of existing antibiotic molecules, attention
      is also directed to alternative strategies to develop antibacterial agents with
      novel mechanisms of action.

PMID- 24133967
TI  - [Epigenetic mechanisms of Alzheimer's disease and related drug research].
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characteristic of
      neurons reducing, senile plaques, neurofibrillary tangles and so on, and the most
      common cause of dementia among the elderly. Many efforts have been made to
      understand the epigenetic mechanisms involved in the development of AD, such as
      gene methylation and histone acetylation, although the exact mechanisms are not
      yet entirely clear. Here, we provide a review of the epigenetic mechanisms and
      related research in AD, which may provide a new direction for the research as
      well as the development of the epigenetic drugs.

PMID- 24133968
TI  - [Application of efficient synthetic techniques in drug research].
AB  - Compound libraries and chemical synthesis play important roles in drug discovery
      and development, and efficient synthetic techniques can greatly facilitate the
      drug research. This review highlights the application of some efficient synthetic
      techniques in drug research including microwave chemistry, click chemistry,
      combinatorial chemistry, cascade reactions and multicomponent reactions, as well
      as the construction of diverse and drug-like compound libraries.

PMID- 24133969
TI  - [Challenges and strategies of drug innovation].
AB  - Drug research involves scientific discovery, technological inventions and product
      development. This multiple dimensional effort embodies both high risk and high
      reward and is considered one of the most complicated human activities. Prior to
      the initiation of a program, an in-depth analysis of "what to do" and "how to do
      it" must be conducted. On the macro level, market prospects, capital required,
      risk assessment, necessary human resources, etc. need to be evaluated critically.
      For execution, drug candidates need to be optimized in multiple properties such
      as potency, selectivity, pharmacokinetics, safety, formulation, etc., all with
      the constraint of finite amount of time and resources, to maximize the
      probability of success in clinical development. Drug discovery is enormously
      complicated, both in terms of technological innovation and organizing capital and
      other resources. A deep understanding of the complexity of drug research and our
      competitive edge is critical for success. Our unique government-enterprise
      academia system represents a distinct advantage. As a new player, we have not
      heavily invested in any particular discovery paradigm, which allows us to select
      the optimal approach with little organizational burden. Virtue R&D model using
      CROs has gained momentum lately and China is a global leader in CRO market.
      Essentially all technological support for drug discovery can be found in China,
      which greatly enables domestic R&D efforts. The information technology revolution
      ensures the globalization of drug discovery knowledge, which has bridged much of
      the gap between China and the developed countries. The blockbuster model and the
      target-centric drug discovery paradigm have overlooked the research in several
      important fields such as injectable drugs, orphan drugs, and following high
      quality therapeutic leads, etc. Prejudice against covalent ligands, prodrugs,
      nondrug-like ligands can also be taken advantage of to find novel medicines. This
      article will discuss the current challenges and future opportunities for drug
      innovation in China.

PMID- 24133970
TI  - [Computational chemistry in structure-based drug design].
AB  - Today, the understanding of the sequence and structure of biologically relevant
      targets is growing rapidly and researchers from many disciplines, physics and
      computational science in particular, are making significant contributions to
      modern biology and drug discovery. However, it remains challenging to rationally
      design small molecular ligands with desired biological characteristics based on
      the structural information of the drug targets, which demands more accurate
      calculation of ligand binding free-energy. With the rapid advances in computer
      power and extensive efforts in algorithm development, physics-based computational
      chemistry approaches have played more important roles in structure-based drug
      design. Here we reviewed the newly developed computational chemistry methods in
      structure-based drug design as well as the elegant applications, including
      binding-site druggability assessment, large scale virtual screening of chemical
      database, and lead compound optimization. Importantly, here we address the
      current bottlenecks and propose practical solutions.

PMID- 24133971
TI  - [Design of next generation antibody drug conjugates].
AB  - Chemotherapy remains one of the major tools, along with surgery, radiotherapy,
      and more recently targeted therapy, in the war against cancer. There have
      appeared a plethora of highly potent cytotoxic drugs but the poor
      discriminability between cancerous and healthy cells of these agents limits their
      broader application in clinical settings. Therapeutic antibodies have emerged as
      an important class of biological anticancer agents, thanks to their ability in
      specific binding to tumor-associated antigens. While this important class of
      biologics can be used as single agents for the treatment of cancer through
      antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is
      often limited. Antitumor antibody drug conjugates (ADCs) combine the target
      specificity of monoclonal antibody (mAb) and the highly active cell-killing
      drugs, taking advantages of the best characteristics out of both components.
      Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by
      arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to
      transport potent payloads to tumor cells. ADCs contain three main components:
      antibody, linker and cytotoxics (also frequently referred as payload). Antibodies
      can recognize and specifically bind to the tumor-specific antigens, leading to an
      antibody-assisted internalization, and payload release. While ADC has
      demonstrated tremendous success, a number of practical challenges limit the
      broader applications of this new class of anticancer therapy, including
      inefficient cellular uptake, low cytotoxicity, and off-target effects. This
      review article aims to cover recent advances in optimizing linkers with increased
      stability in circulation while allowing efficient payload release within tumor
      cells. We also attempt to provide some practical strategies in resolving the
      current challenges in this attractive research area, particularly to those new to
      the field.

PMID- 24133972
TI  - [Application and development of in vitro metabolism study at early drug discovery
      stage].
AB  - Drug metabolism studies, including in vivo and in vitro metabolism studies, are
      significant in the design of candidate compounds and screening of lead compounds
      at drug discovery/development stages. Compared with in vivo metabolism studies,
      in vitro metabolism studies have the advantages of rapidity, simplicity, without
      consumption of large amounts of samples and animals. Moreover, it is convenient
      for researchers to observe the selective interaction between compound and target.
      Therefore, in vitro metabolism studies are appropriate for high throughput
      screening of compounds which are lack of metabolism information and have been
      widely used during drug discovery stages. This article briefly introduced the
      application of in vitro drug metabolism studies based on the metabolic stability,
      reaction phenotyping and metabolic drug-drug interactions, aiming to raise
      valuable evaluation strategies for innovative drug discovery in China.

PMID- 24133973
TI  - [Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors].
AB  - Human protein tyrosine kinases play an essential role in carcinogenesis and have
      been recognized as promising drug targets. By the end of 2012, eight small
      molecule tyrosine kinase inhibitors (TKIs) have been approved by State Food and
      Drug Administration of China for cancer treatment. In this paper, the
      pharmacokinetic characteristics (absorption, distribution, metabolism and
      excretion) and drug-drug interactions of the approved TKIs are reviewed. Overall,
      these TKIs reach their peak plasma concentrations relatively fast; are
      extensively distributed and highly protein bound (> 90%); are primarily
      metabolized by CYP3A4; most are heavily influenced by CYP3A4 inhibitors or
      inducers except for sorafenib; are mainly excreted with feces and only a minor
      fraction is eliminated with the urine; and are substrate of the efflux
      transporters ABCB1 (P-gp) and ABCG2 (BCRP). Additionally, many of the TKIs can
      inhibit some CYP450 enzymes, UGT enzymes, and transporters. Gefitinib, erlotinib,
      dasatinib, and sunitinib are metabolized to form reactive metabolites capable of
      covalently binding to biomolecules.

PMID- 24133974
TI  - [Research progress in co-delivery of gene and chemotherapy drugs with
      nanocarriers for cancer therapy].
AB  - Current trends in nanotechnology and RNA interference technology have made the
      application of nanocarriers (NCS) as a novel gene and drug delivery systems very
      promising for the field of multidrug resistance (MDR) cancer treatment. Co
      delivery of gene and chemotherapy drugs with NCS has a good synergistic effect
      compared with the traditional chemotherapy which can increase the amount of the
      drug distribution in target organ in order to reduce the toxic side effects
      thereby enhancing efficacy. Therefore, the advent of co-delivery systems with NCS
      especially in the clinical treatment of MDR has had a significant impact on the
      cancer treatment.

PMID- 24133975
TI  - [Salvia miltiorrhiza as medicinal model plant].
AB  - Research on medicinal model organism is one of the core technologies to promote
      the modernization of traditional Chinese medicine (TCM). The research progress of
      Salvia miltiorrhiza as medicinal model plant is summarized in this paper. The
      genome of S. miltiorrhiza is small and its life cycle is short, as well as this
      plant can be stably genetically transformed. Because S. miltiorrhiza possesses
      the important medicinal and economic values, recently the transcriptome and
      genome of S. miltiorrhiza have been significantly recovered. The research
      prospect of S. miltiorrhiza as medicinal model plant in TCM was discussed,
      including biosynthesis of active components and their genetic regulation,
      relationship between quality of TCM and ecological environments, and selective
      breeding of good quality lines. Furthermore, as medicinal model plant, the
      construction of mutant library for S. miltiorrhiza, the genome map with high
      quality, and the functional genome should be investigated. Accompanying modern
      investigation of life sciences, the platform for medicinal model plant, S.
      miltiorrhiza, will be promoted to be established. It is important to develop the
      ethnopharmacology and new drugs around the world.

PMID- 24133976
TI  - [Expression of recombinant human kallistatin in Pichia pastoris by high density
      cell culture, and its purification and characterization].
AB  - Kallistatin (Kal) is a negative acute phase endogenous protein which can inhibit
      tumor angiogenesis, growth and metastasis effectively. To express and purify
      recombinant human kallistatin (rHKal), and characterize its biological activity,
      P. pastoris was transformed with pPIC9-Kal/GS115 (His4) to express rHKal. The
      fermentation was carried out in a 7.5 L bioreactor with high density cell
      culture. 1%-2% methanol was added to the medium to induce the expression of
      rHKal. The secretion was purified with phenyl sepharose, G-25 sepharose, heparin
      sepharose and Sephacryl S-100 chromatography. The biological activity of purified
      bulk rHKal on HUVEC was evaluated with MTT and tube formation assays. The final
      expression of rHKal in the supernatant reached 50 mg x L(-1), the purity of bulk
      rHKal after purification was above 98%. A dose-dependent inhibition of rHKal on
      HUVEC proliferation was observed, however, a U-shaped dose-response curve of
      rHKal on capillary formation of HUVEC was revealed. The described protocol
      provides an effective means for preparing rHKal that could be used for anti
      angiogenesis therapy in the future.

PMID- 24133977
TI  - [S632A3 promotes LPS-induced IFN-beta production through inhibiting the
      activation of GSK-3beta].
AB  - LPS stimulation of macrophages production of IFN-beta plays a key role in innate
      immunity defending the microbial invasion. In this study, the effect of S632A3
      promoting LPS-induced IFN-beta production and the underlying mechanism were
      investigated, mRNA level was measured by real-time PCR, cytokine production was
      determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein
      phosphorylation and expression were evaluated by Western blotting. The results
      revealed that S632A3 significantly augmented IFN-beta production by LPS
      stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced
      the threonine 239 phosphorylation of transcription factor c-Jun but increased the
      total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering
      RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment
      IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead
      compound and provides a molecular mechanism by which S632A3 promoted LPS-induced
      IFN-beta production in macrophages through inhibiting the activation of GSK
      3beta.

PMID- 24133978
TI  - [Synthesis and antitumor activity of novel tetrahydro-beta-carboline derivatives
      as KSP inhibitors].
AB  - Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer
      agents that cause mitotic arrest and induce apoptosis of tumor cells. A series of
      novel tetrahydro-beta-carboline derivatives were synthesized as kinesin spindle
      protein inhibitor and evaluated as potential antitumor agents. All compounds
      showed promising KSP inhibitiory activity. Compounds 8 and 9 exhibited better
      antitumor activity (Lung/A549, Stomach/AGS) than CK0106023 with GI50/IC50 values
      (1.07/1.62 and 1.46/3.27 micromol x L(-1), 1.09/>10 and 1.22/6.33 micromol x L(
      1), respectively).

PMID- 24133979
TI  - [Chemical constituents of Dipsacus asper].
AB  - To study the chemical constituents of Dipsacus asper, chromatographic methods
      such as D101 macroporous resin, silica gel, octadecylsilyl (ODS) column
      chromatographic techniques and preparative HPLC were used, and five compounds
      were isolated from 70% (v/v) ethanol extract of the plant. By using spectroscopic
      techniques including 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC and TOF-MS, the
      compounds were identified as 3beta-hydroxy-24-nor-urs-4 (23), 12-dien-28-oic acid
      (1), ursolic acid (2), oleanolic acid (3), 3-O-alpha-L-rhamnosyl(1 --> 3)-beta-D
      glucopyranosyl (1 --> 3)-alpha-L-rhamnosyl (1 --> 2)-alpha-L-arabinopyranosyl
      hederagenin 28-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl ester (4),
      3-O-[beta-D-xylopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 4)] [alpha-L
      rhamnosyl(1 --> 3)]-beta-D-glucopyranosyl (1 --> 3)-alpha-L-rhamnosyl(1 --> 2)
      alpha-L-arabinopyranosyl hederagenin (5), separately. Among them, 1 is a new
      compound, and 2 is isolated from this plant for the first time.

PMID- 24133980
TI  - [Two novel isocoumarins from Erigeron breviscapus].
AB  - Two novel isocoumarins, erigeronone C (1) and D (2), were isolated from the
      ethanol extract of the whole plant of Erigeron breviscapus (Vant.) Hand.-Mazz
      (Compositae). Their structures were respectively elucidated as 8, 9
      dihydroxypyrano [3, 2-c] isochromen-4, 6-dione (1) and 4, 7-dihydroxy-3-(3
      hydroxy-4-oxo-4H-pyran-2-yl)-1H-isochromen-1-one (2) on the basis of spectral
      analyses. Both structures of 1 and 2 possess a gamma-pyrone moiety and that is
      rare in natural products.

PMID- 24133981
TI  - [Effects of six kinds of Chinese herb extracts on the activities of rat liver
      microsomes in vitro].
AB  - Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract,
      Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium
      pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the
      activities of CYP450 isozymes (CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) in rat
      hepatic microsomals were studied by using a UPLC-MS/MS (MRM) and cocktail probe
      substrates method. The results showed that effects of six kinds of Chinese herb
      extracts on each CYP450 isozyme activity were inhibitory. The IC50 of Folium
      Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for
      4.04 microg x mL(-1), which showed the highest inhibition; Trifolium pratense L.
      extract had strong inhibitory action to CYP2D, the IC50 value was 5.73 microg x
      mL(-1); Folium Crataegi extract also had strong inhibitory action on CYP2E1, the
      IC50 value was 10.91 microg x mL(-1). Furthermore, the IC50 of Folium Ginkgo
      extract for the inhibition of rat microsomal CYP3A, 2D, 2E1 activities were
      45.12, 35.45 and 22.41 microg x mL(-1), respectively, and the IC50 of Folium
      Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1
      activity was 32.89 microg x mL(-1). In addition, mechanism of inhibition
      experimental results showed that the inhibiting abilities of Folium Crataegi
      extract and Radix Puerariae extract on each CYP450 isozyme increased with the
      increasing of the preincubation time, therefore, the inhibitory effects were a
      mechanism-based inhibition.

PMID- 24133982
TI  - In vivo effect of triptolide combined with glycyrrhetinic acid on rat cytochrome
      P450 enzymes.
AB  - Triptolide (TP) is a major active component in Tripterygium root, but its
      therapeutic window was very narrow due to its severe multi-organ toxicity. In
      this work, the effect of TP combined with glycyrrhetic acid (GA) on mRNA
      expression and activity of four cytochrome P450 (CYP) enzymes in rat liver was
      studied after intragastric administration of TP (0.05, 0.3 and 0.6 mg x kg(-1) x
      day(-1)) and TP (0.6 mg x kg(-1) x day(-1)) combined with GA (30 mg x kg(-1) x
      day(-1)) for 7 consecutive days. Compared with the control, the high dose of TP
      significantly up-regulated the mRNA expression levels of CYP2E1, 1A2, 3A1 and
      2C11, the co-administration of TP and GA further up-regulated the mRNA expression
      levels of CYP3A1, 2C11 and 2E1 as compared with the high dose of TP. Meanwhile,
      TP at high dose and combined with GA significantly increased CYP3A-associated
      testosterone 6beta-hydroxylation activity (2.2-fold and 4.1-fold, respectively)
      as compared with the control. Because TP is mainly metabolized by CYP3A2 in male
      rats, the present work indicated that TP-induced increase of CYP3A activity might
      be an important reason for the rapidly metabolic clearance of TP in rat liver,
      and GA can reduce the hepatotoxicity of TP by promoting its hepatic metabolic
      clearance. Furthermore, the results also suggest that the drug interactions might
      be occurred when TP and GA were co-administered with other CYP3A substrate drug.

PMID- 24133983
TI  - [Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane
      modified liposomes].
AB  - The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane
      modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L
      was prepared by organic solvent injection method. Transmission electron
      microscope, dynamic light scattering and electrophoretic light scattering were
      employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory
      effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA
      PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were
      detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice
      were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal
      saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor
      volume, mice weight, inhibition rate of tumor and life span were measured at the
      end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were
      significantly lower than that of DCT-I and DCT-L, without hemolysis reaction
      observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and
      FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at
      79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated
      mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA
      PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers
      for DCT in the treatment of tumor.

PMID- 24133984
TI  - [Powder modification technology used for the preparation of the hydrophilic
      decoction pieces of indigo naturalis and the modification principle].
AB  - The hydrophilicity of the normal decoction pieces (NDP) of Indigo Naturalis is
      not good, therefore, it is not suit for decoctions. In this paper, powder
      modification technology is used and some NDP and alcohol are ground together in
      the vibromill to prepare the hydrophilic decoction pieces (HDP) of Indigo
      Naturalis. Initially, the properties of NDP, ultrafine decoction pieces (UDP) and
      HDP are compared, the hydrophilicity of UDP was promoted slightly, that of HDP is
      promoted dramatically. Then, three batches of Indigo Naturalis are prepared to
      HDP separately, but there is no obvious difference in the contact angle.
      Furthermore, the size distribution, surface area and micro-shape of HDP are
      bigger than that of UDP and smaller than NDP. The contents of indigo and
      indirubin in three decoction pieces are the same, as well as the species of
      inorganic substance, although there is a little difference in the proportion of
      five inorganic substances. The fact suggests the change of physical state and the
      qualitative and quantitative change of organism and inorganic substances are not
      the main factors to influence the hydrophilicity. In addition, hydroxyl,
      methylene and methyl can be identified at the wavenumber of 3 356 cm(-1) and 1
      461 cm(-1) in infrared spectrum; the content of alcohol in HDP is 0.67% measured
      by gas chromatogram. The stability of HDP in the heating condition is studied,
      the fact suggests the hydrophilic effect of HDP at 40 degrees C is relatively
      stable. All above research suggests that the alcohol is the main factor to
      influence the hydrophilicity and maybe the intermolecular force which fixed
      alcohol molecule on the surface of Indigo Naturalis is the basic principle to
      produce the hydrophilicity.

PMID- 24133985
TI  - [Real-time UV imaging of chloramphenicol intrinsic dissolution characteristics
      from ophthalmic in situ gel].
AB  - In this paper, chloramphenicol was selected as a model drug to prepare in situ
      gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was
      evaluated using the surface dissolution imaging system. The results indicated
      that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel
      decreased significantly when the poloxamer concentration increased. The addition
      of the thickener reduced the intrinsic dissolution rate of chloramphenicol
      thermosensitive gel, wherein carbomer had the most impact. Different dilution
      ratios of simulated tear fluid greatly affected gel temperature, and had little
      influence on the intrinsic dissolution rate of chloramphenicol from the
      thermosensitive in situ gel. The pH of simulated tear fluid had little influence
      on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel.
      For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in
      weak acidic and neutral simulated tear fluids were slower than that in weak
      alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of
      chloramphenicol from in situ gel was dependent on formulation and physiological
      factors. With advantages of small volume sample required and rapid detection, the
      UV imaging method can be an efficient tool for the evaluation of drug release
      characteristics of ophthalmic in situ gel.

PMID- 24133986
TI  - [Expression of subtilisin-like protease gene from Hirsutella sinensis before and
      after infecting Hepialus gonggaensis].
AB  - To address the role of Pr1 gene in the process of Hirsutella sinensis infecting
      Hepialus gonggaensis, differential expression of subtilisin-like protease gene
      was detected. In the present study, Pr1 gene analogues from H. sinensis were
      obtained by PCR strategy using specific primers designed from conserved regions
      of Pr1 gene reported in the GenBank. Then we detected the changes in the
      expression of Pr1 gene before and after infecting H. gonggaensis using real-time
      quantitative PCR. We obtained the partial sequence of Pr1 gene with the length of
      535 bp (GenBank accession: KC009680). Real-time PCR results showed that the
      expression level of Pr1 gene was significantly different among 8 samples (P <
      0.01). Pr1 gene showed the obvious higher expression level (2-3 folds) after
      infecting the H. gonggaensis, suggesting that the Pr1 gene may play an important
      role in the process of H. sinensis infecting H. gonggaensis. The present study
      paves a way for further identification on infectivity assessment of H. sinensis.

PMID- 24133987
TI  - [Construction and tobacco transformation of COR and BBE genes hairpin RNA vector
      of Papaver somniferum].
AB  - The gene expressions of codeinone reductase (COR) and berberine bridge enzyme
      (BBE) in Papaver somniferum were blocked by RNA hairpin of RNA interference
      (RNAi). The complete sequences of COR and BBE genes were cloned by reverse
      transcription-polymerase chain reaction (RT-PCR), the results of homology
      comparison revealed that the cloned COR and BBE genes had high homology with the
      other gene family members reported in the GenBank. The target sequences of COR
      and BBE genes were screened in accordance with the design principle of RNAi, a
      643 bp fusion gene was obtained by the method of overlapping PCR, then plant
      expression vector ihpRNA was constructed based on intermediate vector pHANNIBAL
      and plant expression vector pCEPSPS. With that 78 transgenic plants were obtained
      through Agrobacterium-mediated and 17 positive plants were screened by PCR, that
      could initially indicate that the target fragments of COR and BBE gene had been
      integrated into tobacco genome.

PMID- 24133988
TI  - [Oil of Piper longum unsaponifiable matter prevents cholesterol gallstone
      formation].
AB  - To observe the effect of various doses of oil of Piper longum unsaponifiable
      matter (OPUM) to cholesterol gallstones in experimental mice. C57BL/6 mice (n =
      60) were randomly divided into 6 groups: control group, model group, OPUM (15, 30
      and 60 mg x kg(-1)) group and ursodeoxycholic acid (UDCA, 60 mg x kg(-1)) group,
      administered for 10 weeks. The level of serum lipid and liver function enzymes
      were tested. The gallbladder was removed and bile was obtained by centrifugation.
      Next, the levels of the bile total cholesterol (TC), phospholipid (PL) and bile
      acid (TBA) were measured. The indicators of lipid peroxidation were determined
      and cholesterol saturation index (CSI) was calculated. The liver histological
      changes were observed by HE staining. The results showed that serum TC, TG
      (triglycerides) and AST (aspartate transaminase) contents, gallbladder
      cholesterol crystallization and CSI increased significantly (P < 0.05). In
      addition, the activity of SOD decreased significantly and MDA content increased
      significantly in liver (P < 0.05). HE staining results showed that the hepatic
      cord disorder and intracellular lipid droplets increased significantly. All
      results indicate that lithogenic diet lead to the formation of cholesterol
      gallstones. In OPUM (30 and 60 mg x kg(-1)) group, serum TC, TG and AST content,
      gallbladder cholesterol crystallization and CSI decreased significantly, the
      activity of SOD increased significantly and MDA content decreased significantly.
      HE staining results showed that OPUM can improve the morphology of liver cell,
      reduce the degree of hepatic cord disorders and restore the cell morphology close
      to normal. The cause of OPUM prevents cholesterol gallstone formation maybe due
      to protect the integrity of the liver cells, lower CSI, and reduce cholesterol
      crystal formation and hence prevent cholesterol gallstone formation.

PMID- 24133989
TI  - [Study on rapid propagation of Scutellaria baicalensis variation].
AB  - OBJECTIVE: To establish and optimize the technology of taking root and promoting
      seedlings of white flower Scutellaria baicalensis test tube plantlet, and provide
      the theory and technology base for efficient factorization production system of
      white flower Scutellaria baicalensis. METHODS: Stem segments with axillary bud
      were cultured onto the different basic medium with different kinds and
      concentration of cytokinin and auxins to take root and produce strong seedling.
      RESULTS: The suitable culture medium for taking root of white flower Scutellaria
      baicalensis was 1/2 MS (all substance reduced half) + IBA 0.02 mg/L + sucrose 2%,
      the induction rate of root was 100%; The best medium for promoting seedling was
      1/2 MS (all substance reduced half) + PP333 0.2 mg/L + IBA 0.02 mg/L + sucrose
      2%, the seedling was green, the internode was normal, and its growth was vigorous
      and healthy. CONCLUSION: 1/2 MS (all substance reduced half) culture medium and
      relatively low concentration of sucrose is beneficial to inducing roots; Media
      adding appropriate concentration of IBA can significantly increase the root
      induction rate, the seedling has many stout roots; PP333 has dwarfing effect on
      seedlings and suitable concentration of PP333 can significantly improve the
      quality of the plantlets. A good technology of taking root and producing strong
      test tube plantlets is established.

PMID- 24133990
TI  - [Effect of salt stress on DNA methylation in Isatis indigotica].
AB  - OBJECTIVE: To investigate the effect of salt stress on DNA methylation in Isatis
      indigotica. METHODS: Methylation sensitive amplification polymorphism (MSAP)
      approach was used in this study. RESULTS: By using 15 pairs of selective primers
      combinations, a total of 632 MSAP bands were obtained in Isatis indigotica genome
      under salt stress. In all, 44 (6.9%) CCGG sites displayed cytosine methylation
      changes under salt stress. Among these sites, 31(4.9%) CCGG sites underwent
      hypermethylation changes and 13 (2.0%) CCGG sites underwent demethylation
      changes. CONCLUSION: This result provides evidence for DNA methylation remodeling
      occurring immediately after salt stress affects Isatis indigotica.

PMID- 24133991
TI  - [Comparative study on the protein maps of different parts of Cervus nippon antler
      by two-dimensional electrophoresis].
AB  - OBJECTIVE: To optimize the two-dimensional electrophoresis (2-DE) method for the
      proteome analysis of the Cervus nippon antler, and compare the protein maps of
      different parts of Cervus nippon antler. METHODS: The total proteins of Cervus
      nippon antler were extracted by protein lysate containing 7 mol/L Urea, 4% CHAPS,
      2 mol/L Thiourea, 65 mmol/L DTT, 1 mmol/L PMSF and 0.2% Bio-Lyte. The proteins
      were separated by immobilized pH 3 - 10 linear gradient (IPG), 7 cm strips as the
      first dimension. Isoelectric focusing conditions were optimized. 12% SDS-PAGE was
      used as the second dimension electrophoresis. The gels were stained with
      Coomassie brilliant blue and analyzed by PDQuest analysis software. RESULTS: The
      contents of total protein and the numbers of protein points of three different
      parts of Cervus nippon antler reduced gradually from the top to the bottom.
      Comparing three maps of different parts of Cervus nippon antler, there were 18
      different protein points. Isoelectric point, molecular weight and gray value of
      each different protein point were calculated. CONCLUSION: An optimized two
      dimensional electrophoresis method for the proteome analysis of the Cervus nippon
      antler is established. The 2-DE profiles of different parts of Cervus nippon
      antler exist obvious differences. The different protein points can be used as
      reference for Cervus nippon antler quality control and evaluation.

PMID- 24133992
TI  - [Effects of PEG and NaCl stress on the contents of indigotin and indirubin in
      Isatis indigotica tetraploids].
AB  - OBJECTIVE: To provide a reference evidence for choosing salt-resistent and
      drought-resistent varieties of Isatis indigotica Fort.. METHODS: The tissue
      culture seedlings of different Isatis indigotica tetraploids were used as plant
      materials. The diploid was used as CK, which were cultured for 30 days. 2 g/L
      NaCl and 15% PEG-6000 were used as stress treatment respectively for 12 hours,
      then poured out the solution, the materials were continuously cultured for 7
      days. The contents of indirubin and indigotin were determined by HPLC. RESULTS:
      The contents of indigotin and indirubin of DB3, DB5 and DB12 with PEG treatment
      and DB2, DB3 and DB12 with NaCl treatment were increased. CONCLUSION: DB3 and
      DB12 can be further studied as reproduction materials.

PMID- 24133993
TI  - [Determination of organochlorine pesticide residues in the roots of Zanthoxylum
      nitidum by GC-MS].
AB  - OBJECTIVE: To determine the contents of organochlorine pesticide residues in the
      roots of Zanthoxylum nitidum and provide scientific foundation for the quality
      control and standard establishment. METHODS: GC-MS method with selected ion
      monitoring (SIM) mode was used to analyze the contents of organochlorine
      pesticide residues in the roots of Zanthoxylum nitidum. The samples were
      extracted with acetone and ultrasonic vibrations, and the analytical samples were
      purified by anhydrous sodium sulfate-anhydrous magnesium sulfate -PSA -C18
      PestiCarb -phase extraction (SPE) cartridge. RESULTS: Eight kinds of
      organochlorine pesticide were detected simultanously. Small amounts of OP-DDT
      were detected in samples 1, 4, 5, 6, 11 and 12, no organochlorine pesticide
      residue was detected in other samples. The RSD of precision ranged from 0.89% to
      2.21%, and the average recovery ranged from 85.33% to 103.70%, with the RSD less
      than 4%. CONCLUSION: The contents of organochlorine pesticide residues in the
      roots of Zanthoxylum nitidum are less than 0.2 ppm. This method is sensitive,
      good purifying, and suitable for analyzing organochlorine pesticide residues in
      the roots of Zanthoxylum nitidum.

PMID- 24133994
TI  - [Study on species and distribution of flora of national rare and endangered
      medicinal plant in the Three Gorges area].
AB  - According to the China Plant Red Data Book and National Key Protected Wild
      Plants, the distribution of the rare and endangered plants and national
      conservative plants in the Three Gorges area were investigated and statistically
      analyzed. Its floristic composition and characteristics of geographical
      distribution were explored. As a result, a total of 97 species of medicinal flora
      belonging to rare and endangered national protection plants were found in the
      Three Gorges area. They come from 81 genera of 46 families. Their vertical
      distribution is obvious and horizontal distribution has discontinuous overlap.
      There are many ancient relict medicinal plants in the Three Gorges area. These
      medicinal plants have obvious temperate characteristics, and are easily found at
      warm and moist ravines and hillsides; The proportion of tree is much higher than
      that of herb, vine, shrub and fern. Most of them belong to specific and monotypic
      genera.

PMID- 24133995
TI  - [Effect of honey-toasting on the constituents and contents of aristolochic acid
      analogues in aristolochiae fructus].
AB  - OBJECTIVE: To evaluate the degree of de-toxification of Aristolochiae Fructus by
      honey-toasting technology from chemical viewpoint. METHODS: The contents of
      aristolochic acid analogues (AAs) in Aristolochiae Fructus and its honey-toasted
      product were determined by HPLC, and the degree of de-toxification was evaluated
      comprehensively. RESULTS: After honey-toasted, the contents of AAs decreased to
      varying degrees, and some new compounds were found. CONCLUSION: The constituents
      and contents of Aristolochiae Fructus change after honey-toasted, which indicate
      honey-toasting can reduce the toxicity of Aristolochiae Fructus.

PMID- 24133996
TI  - [Optimization of wine-roasting technology of coptidis rhizoma using orthogonal
      design].
AB  - OBJECTIVE: To optimize the processing technology of Coptidis Rhizoma roasting
      with yellow rice wine. METHODS: The total content of four kinds of alkaloids was
      used as index. Orthogonal design was applied to study the processing technology
      of Coptidis Rhizoma roasting with yellow rice wine. L9 (3(4)) orthogonal table
      was decided with three factors: roasting temperature, roasting time and the
      amount of yellow rice wine. RESULTS: Of the three factors, only B factor
      (roasting time) had obvious effect on the total content of four kinds of
      alkaloids. CONCLUSION: The optimal processing technology is as follows: Coptidis
      Rhizoma should be roasted with 15% yellow rice wine for 30 min at 150 degrees C.

PMID- 24133997
TI  - [Research on HPLC fingerprint of Rheum palmatum from Gansu Province called "quan
      shui-da-huang"].
AB  - OBJECTIVE: To establish an analysis method for HPLC fingerprint of Rheum palmatum
      collected from Gansu province (called "Quan-shui-da-huang"), and provide basis
      for quality control of Quan-shui-da-huang. METHODS: The Cosmosil 5C18-PAQ column
      (250 mm x 4.6 mm, 5 microm) was used with the mixture of 0.1% acetic acid and
      acetonitrile as mobile phase in a gradient elution mode. The flow rate was 1
      mL/min, column temperature was 30 degrees C and detection wavelength was set at
      280 nm. The similarity evaluation, principal component analysis (PCA) and cluster
      analysis of crude drugs collected from different habitats were carried out.
      RESULTS: The analysis method of HPLC fingerprint was set up. The characteristic
      fingerprint was obtained by chemometrics methods. CONCLUSION: Under the selected
      chromatographic conditions, constituents in Rheum palmatum can be separated well.
      This method can be used for the quality control of Quan-shui-da-huang.

PMID- 24133998
TI  - [Evaluation of quality coherence of prepared slices of polygoni cuspidati rhizoma
      commercially available in China based on HPLC fingerprint].
AB  - OBJECTIVE: To evaluate the quality coherence of the prepared slices of Polygoni
      Cuspidati Rhizoma commercially available in China and provide a reference for
      their quality evaluation. METHODS: The fingerprints were obtained using HPLC
      method, and analyzed with Chromatographic Fingerprint Similarity Evaluation
      System (2004A Version) provided by Chinese Pharmacopoeia Commission. The
      experiment was carried out with an Agilent TC-C18 column (250 mm x 4.6 mm, 5
      microm) using acetonitrile-0.05% aqueous solution of phosphoric acid as mobile
      phase at the flow rate of 1.0 mL/min, detection wavelength of 230 nm, and
      temperature of 25 degrees C. RESULTS: The fingerprint for Polygoni Cuspidati
      Rhizoma was established. 21 common characteristic peaks were identified and the
      similarities of 24 batches of prepared slices of Polygoni Cuspidati Rhizoma were
      between 0.882 - 0.988. CONCLUSION: The quality of the prepared slices of Polygoni
      Cuspidati Rhizoma commercially available in China is comparable.

PMID- 24134000
TI  - [Study on species identification of commercial drug cudraniae tricuspidatae radix
      et caulis and its medicinal parts].
AB  - OBJECTIVE: To establish an identification method of Cudrania tricuspidata and
      Cudrania cochinchinensis, and their medicinal parts, and analyse the species of
      commercial drug Cudraniae Tricuspidatae Radix et Caulis. METHODS: TLC and First
      order Derivative UV Spectrophotometry were used. RESULTS: Commercial drugs 5, 6,
      7 and 9 belonged to the stem of Cudrania cochinchinensis, commercial drug 1, 2, 3
      ,4 and 8 were neither Cudrania tricuspidata nor Cudrania cochinchinensis.
      CONCLUSION: Cudrania tricuspidata and Cudrania cochinchinensis can be identified
      by TLC, as well as the medicinal parts. UV Spectrophotometry can't be applied to
      variety identification but can be used for identifying the medicinal parts. It's
      more accurate and reliable for identifying Cudrania tricuspidata and Cudrania
      cochinchinensis, and the medicinal parts by combined using TLC and UV. This study
      provides a scientific and effective method for species identification and
      medicinal part analysis of commercial drug Cudraniae Tricuspidatae Radix et
      Caulis.

PMID- 24133999
TI  - [Study on quality standard for mori cortex].
AB  - OBJECTIVE: To establish a new evaluation model and compare the differences of
      Mori Cortex from different habitats at different harvest time. METHODS: TLC
      method was used to identify sanggenon D in the sample with silica gel G plate and
      a mixture of chloroform-methanol-formic acid (5: 1:0. 3) as a developing solvent.
      UV was used for determination the centent of total flavonoids of Mori Cortex with
      sanggenon C as the reference substance. HPLC was applied for determination the
      contents of sanggenons C, D and DNJ of Mori Cortex. RESULTS: In the TLC
      chromatogram, sanggenon D showed a distinct fluorescence spot under UV 365 nm
      with good separation. In UV, sanggenon C calibration curve showed a good linear
      relationship at the range of 146.8 - 734.0 microg/mL, the average recovery was
      97.4% (RSD = 2.1%); For the HPLC quantitation method, sanggenons C, D and DNJ
      showed good linear within the scope of 700 - 4 000 microg, 500 - 3 000 microg and
      4.8 - 96 microg, respectively. The average recovery of sanggenons C, D and DNJ
      were 98.8% (RSD = 2.6%), 99.1% (RSD = 2.2%) and 98.9% (RSD = 1.7%), respectively.
      The contents of index components in samples from different habitats at different
      harvest time were different. CONCLUSION: The established method is reliable and
      accurate. It can be used for quality control of Mori Cortex.

PMID- 24134002
TI  - [Study on the chemical constituent from the dichloromethane extract of the pine
      needle of Cedrus deodara (II)].
AB  - OBJECTIVE: To study the chemical constituents of the dichloromethane extract from
      pine needles of Cedrus deodara. METHODS: The chemical constituents were isolated
      and purified from the dichloromethane extract of pine needles by chromatography
      on silica gel and Sephadex LH-20. Their structures were elucidated by analysis of
      spectral data and chemical properties. RESULTS: Seven compounds were isolated and
      their chemical structures were identified as ferulic acid (1), osthole (2), beta
      phenylacrylic acid (3), paeonol (4), beta-sitosterol (5), magnolol (6) and
      honokiol (7). CONCLUSION: Compounds 1 - 4, 6 and 7 are isolated from this plant
      for the first time.

PMID- 24134001
TI  - [Study on chemical constituents of Callicarpa peii].
AB  - OBJECTIVE: To study the chemical constituents of Callicarpa peii. METHODS: The
      chemical constituents were isolated and purified by chromatographic methods and
      elucidated by spectral analysis, including UV, IR, MS, 1H-NMR and 13C-NMR.
      RESULTS: Ten compounds were obtained and identified as oleanolic acid (1), 2beta,
      3beta,19alpha-trihydroxy-12-en-28-ursolic acid (2), luteolin -7,4'-dimethylether
      (3), luteolin -3', 4', 7, -trimethylether (4), luteolin -4'-methylether (5),
      hydnocarpin (6), luteolin (7), lyoniresinol 3alpha-O-beta-D-glucopyranoside (8),
      kelampayoside A (9), kaempferol -3-O-glucuronide (10). CONCLUSION: All these
      compounds are isolated from Callicarpa peii for the first time and compounds 3,
      4, 6, 8 and 10 are isolated from this genus for the first time.

PMID- 24134004
TI  - [Research on the correlation between microscopic characteristic constant and
      chemical component of sophorae flos].
AB  - OBJECTIVE: To explore the correlation between microscopic characteristic constant
      and chemical component of Sophorae Flos. METHODS: Capacity analysis was used to
      quantify pollen grains of Sophorae Flos. The content of total flavonoids was
      determined by UV method. The data were analyzed by SPSS statistics software.
      RESULTS: In Sophorae Flos, the microscopic characteristic constant of pollen
      grains and the content of total flavonoids were significantly correlated.
      CONCLUSION: Determination of microscopic characteristic of pollen grains can be
      applied to the quality control of Sophorae Flos.

PMID- 24134003
TI  - [Chemical constituents of roots of Celastrus orbiculatus].
AB  - OBJECTIVE: To study the chemical constitutes of roots of Celastrus orbiculatus.
      METHODS: The compounds were isolated by column chromatography and identified by
      spectroscopic methods including IR, MS and NMR. RESULTS: Nine compounds were
      isolated and identified as sugiol (1), friedelane-3-one (2), salapermic acid (3),
      28-hydroxyfriedelane-3-one (4), pristimerin (5), celastrol (6), beta-sitosterol
      (7), beta-daucosterol (8) and benzoic acid (9), respectively. CONCLUSION:
      Compounds 2 and 4 are isolated from this plant for the first time.

PMID- 24134005
TI  - [Study on volatile components from flowers of Gymnema sylvestre].
AB  - OBJECTIVE: To analyze the volatile components from flowers of Gymnema sylvestre.
      METHODS: Volatile components of flowers of Gymnema sylvestre were extracted by
      water vapor distilling, and the components were separated and identified by GC
      MS. RESULTS: 55 components were separated and 33 components were identified,
      accounting for 88.73% of all quantity. The principal volatile components are
      Phytol, Pentacosane, 10-Heneicosene (c, t), 3-Eicosene, (E) -and 2-Methyl-Z-2
      docosane. CONCLUSION: The research can pro-vide scientific basis for chemical
      component research of flowers of Gymnema sylvestre.

PMID- 24134006
TI  - [Analysis of polysaccharide and lipid components of cinnamomi cortex by GC-MS].
AB  - OBJECTIVE: To study the polysaccharide and lipid components of Cinnamomi Cortex
      by GC-MS and provide experimental evidence for its exploitation. METHODS: The
      polysaccharide components of Cinnamomi Cortex were extracted,and hydrolyzed with
      trifluoroacetic acid (TFA) and followed by adding hydroxylamine hydrochloride,
      pyridine and acetic anhydride acetylation for reaction. After that, spectrometry
      of polysaccharides was measured by GC-MS. Lipid components were esterified and
      identified by GC-MS. RESULTS: 6 kinds of polysaccharide components were
      identified by GC-MS. D-glucofuranose accounted for 38.64%, which was the most
      proportion. 13 kinds of fatty acids were identified, accounted for 72.68% in
      total lipids. 5 kinds of unsaturated fatty acids accounted for 13.83% and 8
      saturated fatty acids accounted for 58.85%. CONCLUSION: There are many kinds of
      polysaccharide and lipid components in Cinnamomi Cortex and GC-MS can analyze the
      polysaccharide and lipid components of Cinnamomi Cortex effectively.

PMID- 24134007
TI  - [Simultaneous determination of formononetin, calycosin and isorhamnetin from
      Astragalus mongholicus in rat plasma by LC-MS/MS and application to
      pharmacokinetic study].
AB  - OBJECTIVE: To establish a method to determine the concentration of formononetin,
      calycosin and isorhamnetin from Astragalus mongholicus in rats' plasma using LC
      MS/MS and calculate their pharmacokinetic parameters. METHODS: The contents of
      formononetin, calycosin and isorhamnetin in plasma were detected before and 24 h
      after 10 rats were treated with 10 g/kg Astragalus mongholicus. Rutin was used as
      internal standard. Agilent 1 200 HPLC system with Alltima C18 (150 mm x 2.1 mm, 5
      microm) was used. Mobile phase was methanol-water solution with gradient elute at
      a flow rate of 0.3 mL/min. The column temperature was 40 degrees C. The LC-MS/ MS
      system was operated using an electrospray ionization probe in negative ion mode;
      Scan mode: multiple reaction ion monitoring (MRM) mode. The ion of monitor: m/z
      267.0 --> 251.9 for formononetin, m/z 283.1 --> 268.2 for calycosin, m/z 315.4 -
      > 300.1 for isorhamnetin and m/z 609.4 --> 300.1 for rutin (internal standard),
      respectively. RESULTS: The linear range of formononetin, calycosin and
      isorhamnetin was 5 - 1 000 (r = 0.9996), 3.91 - 500 (r = 0.9989) and 0.5 - 100
      ng/mL (r = 0.9992), respectively. The lowest limit of quantification (LLOQ) of
      formononetin, calycosin and isorhamnetin was 0.625, 0.5 and 0.1 ng/mL,
      respectively. The pharmacokinetic parameter, t(1/2beta), of formononetin,
      calycosin and isorhamnetin was (10.43 +/- 2.94), (6.91 +/- 1.33) and (5.07 +/-
      1.21) h, respectively. The C(max) of formononetin, calycosin and isorhamnetin was
      (398.5 +/- 103.7), (138.7 +/- 32.8) and (58.3 +/- 14.5) ng/mL, respectively. The
      AUC(0 -> 12h), of formononetin, calycosin and isorhamnetin was (1238.8 +/-
      311.3), (669.5 +/- 159.7) and (274.1 +/- 83.9)ng x h/mL, respectively.
      CONCLUSION: A sensitive, accuracy and suitable LC-MS/MS method for determination
      of formononetin, calycosin and isorhamnetin is developed and successfully applied
      to the pharmacokinetic study of 10 g/kg Astragalus mongholicus after oral
      administration in rats.

PMID- 24134008
TI  - [Effects of plumbagin on expression of TNF-alpha and PDGF-BB in human hepatic
      stellate cells activated by leptin].
AB  - OBJECTIVE: To investigate the effect of plumbagin on the expression of TNF-alpha
      and PDGF-BB in human hepatic stellate cells (HSC-LX2) activated by Leptin.
      METHODS: HSC-LX2 were cultured in vitro and stimulated by Leptin for 24 hours
      then treated with different concentrations of plumbagin for 24 hours, the
      expressions of TNF-alpha mRNA and PDGF-BB mRNA were determined by Realtime
      quantitative PCR, the protein expressions of TNF-alpha and PDGF-BB were
      determined-by Western blotting. RESULTS: The expressions of TNF-alpha mRNA and
      PDGF-BB mRNA of treatment groups were significantly reduced, especially in high
      dose group (P < 0.01), and Western blotting analyses revealed similar trends in
      protein expression. CONCLUSION: Plumbagin may prevent the formation of hepatic
      fibrosis and its mechanism may be related to decreasing the level of mRNA of TNF
      alpha and PDGF-BB and the protein of PDGF-BB.

PMID- 24134009
TI  - [Effect of Helicteres angustifolia on rats with ulcerative colitis].
AB  - OBJECTIVE: To investigate the effect of aqueous extract of Helicteres
      angustifolia (AEHA) on rats with ulcerative colitis (UC) and its mechanism.
      METHODS: SD rats were randomly divided into 6 groups normal control group, the
      model group, SASP group and 21.6, 10.8, 5.4 g/kg AEHA group with 10 rats in each
      group. UC was induced by clyster with 2, 4,6-trinitrobenzesulphonic acid (TN-BS)
      in rats. Rats were given AEHA by gavage for 3 weeks, and sacrificed at day 22nd
      to determine the expressions of IL-10, IL-6 and TNF-alpha in blood. Colon tissue
      pathological changes were investigated. RESULTS: Compared with the control group,
      the expression of IL-10 was increased, the expressions of IL-6 and TNF-alpha were
      decreased in AEHA treatment groups. The colon tissue damages and the symptoms of
      UC rats were improved. CONCLUSION: AEHA can keep balance of inflammatory factors
      in blood of UC rats, and improve it's colon tissue damages and symptoms.

PMID- 24134010
TI  - [Effect of elemene on reversing chemoresistance to adriamycin in human stomach
      cancer cell line].
AB  - OBJECTIVE: To investigate the effect of elemene on reversing chemoresistance to
      adriamycin (ADM) in human stomach cancer cell, and explore its possible
      mechanism. METHODS: SGC7901/ADM were divided imto two groups: control group and
      elemene treatment group. The cytotoxicity of ADM on SGC7901/ADM was determined by
      MTT assay. The activity of nuclear factor-kappa B (NF-kappaB) was measured by
      immunohistochemical staining. The apoptosis rate of stomach cancer cell line was
      determined by flow cyotometric analysis. RESULTS: The immunohistochemical
      staining result showed that the activity of NF-kappaB in SGC7901/ADM was
      increased after treated with ADM for 9 - 12 h, while that of the elemene
      treatment group decreased with the increasing of the elemene concentration and
      the lowest level was 8 - 12%. The apoptosis rate of SGC7901/ADM stomach cancer
      cell line was increased with the increasing of elemene concentration. At the same
      elemene concentration, the apoptosis rate increased with ADM treatment time
      prolonged. MTT result showed that the non-cytotoxic dose of elemene had
      synergistic effect on rilling SGC7901/ADM stomach cancer cell line and was in a
      dose-dependant manner. CONCLUSION: The inhibitory effect of elemene on reversing
      chemoresistance to ADM in human stomach cancer cell line maybe related to
      inhibiting NF-kappaB activity.

PMID- 24134011
TI  - [Effect of total saponin of aralia taibaiensis on proliferation of leukemia
      cells].
AB  - OBJECTIVE: To investigate the effect of total saponin of Aralia Taibaiensis on
      the leukemia cells and explore the mechanisms of early apoptosis. METHODS: The
      leukemia cells lines K562 and U937 were cultured in vitro and divided into 2
      groups: control group and treatment group. The proliferation inhibition of
      leukemia cells was measured by MTT assay. K562 cells morphological changes were
      observed under the reverse microscope; Flow cytometry (FCM) was used to detect
      the influence of total saponin of Aralia Taibaiensis on changes of mitochondrial
      membrane potential in K562 cells. The expression of protein BCL-2 and BAX in K562
      cells was investigated by immunohistochemistry. RESULTS: The total saponin of
      Aralia Taibaiensis had significant inhibitory effects on K562 and U937 cell
      lines, and the inhibitory effects on these two cells lines presented time
      dependent and dose-dependent manner. The results by inverted microscope were
      consistent with that of the MTT assay. FCM analysis showed that total saponin of
      Aralia Taibaiensis could induce mitochondrial membrane potential of K562 cells.
      Compared with control group, the expression of BCL-2 in treatment group was down
      regulated, the expression of BAX was significantly up-regulated. CONCLUSION: The
      total saponin of Aralia Taibaiensis can inhibit two kinds of leukemia cells lines
      in vitro, and the mechanism may be related to promoting the early apoptosis of
      K562 cells.

PMID- 24134012
TI  - [Preparation technology of total coumarins from Laportea bulbifera].
AB  - OBJECTIVE: To investigate the preparation process of total coumarins from
      Laportea bulbifera. METHODS: The optimum condition for the extraction of total
      coumarins was studied using the orthogonal test, and the extracts was purled with
      different kinds of macroporous resins. The content of total coumarins was
      detected by ultraviolet spectrophotometry. RESULTS: The optimum extraction
      process was as follows: three-time circumfluence with 4 times volume of 75%
      ethanol for 1.5 h each time. HPD300 macroporous resin was the optimum one for the
      separation and purification of total coumarins. The extraction condition was
      loading 30 mL of 0.4 g/mL the crude drug, flowing at 2BV/h, then edulcorating
      with 4 times volume of distilled water and eluting with the same volume of 75%
      ethanol. The yield rate was more than 52%. CONCLUSION: This method is suitable
      for the preparation of total coumarins in Laportea bulbifera, and the process is
      stable and repeatable.

PMID- 24134013
TI  - [Influence of superfine grinding on micromeritic properties of Scutellaria
      baicalensis].
AB  - OBJECTIVE: To study the micromeritic properties of different particle size of
      Scutellaria baicalensis and provide a basis for being directly used or as raw
      material of Chinese herba preparation. METHODS: Size distribution, surface area
      and pore volume, contact angle, angle of repose and bulk density, moisture
      absorption, micromorphology, Infrared spectrum, HPLC fingerprint were used to
      evaluate the differences of micromeritic properties of 4 kinds of Scutellaria
      baicalensis superfine grinding. RESULTS: With the particle size of powders
      decreased, size distribution and bulk density decreased, the surface area and
      pore volume, contact angle and moisture absorption increased, angle of repose
      first increased and then decreased. Infrared spectrum and HPLC fingerprint showed
      no change of chemical composition of Scutellaria baicalensis. CONCLUSION:
      Different particle size of Scutellaria baicalensis leads to the differences of
      micromeritic properties. Superfine grinding III is determined as a better
      particle size.

PMID- 24134014
TI  - [Optimization the formulation of Eisemia foetida protein burn spray by response
      surface methodology].
AB  - OBJECTIVE: To optimize the formulation of Eisemia foetida protein (EFP) burn
      spray. METHODS: A five-factor, three-level response surface method was employed;
      The response variable was the proliferation effect of EFP on NIH3T3 cells.
      RESULTS: The optimization formulation was as follows: the proportion of EFP,
      glycerol and mannitol was 0.91%, 1.42% and 5%, respectively; 0.02 mol/L Na2 HPO4
      and 0.01 mol/L citric acid buffer system corresponding pH value was 7.0.
      CONCLUSION: The response surface method is reliable, efficient and suitable for
      optimizing the formulation of EFP burn spray.

PMID- 24134015
TI  - [Adsorption and isolation of macroporous resin for three isoflavonoids from
      puerariae lobatae radix].
AB  - OBJECTIVE: To study the adsorption function of macroporous resins for the
      separation and purification of three isoflavonoids (3'-hydroxypuerarin, puerarin,
      daidzin) in Puerariae Lobatae Radix. METHODS: The contents of 3'-hydroxypuerarin,
      puerarin, daidzin were determined by HPLC. D101, AB-8, XDA-5, HP-20 and other
      five resins were systematically investigated for their adsorption capability,
      adsorption isothermal curve, adsorption and elution properties with static and
      dynamic experiments. RESULTS: Experimental results showed that macroporous resin
      XDA-5 owned optimum adsorption and elution parameters. Optimal conditions for
      adsorption and elution the three components were: per 1 mL solution contained
      Puerariae Lobatae Radix 0.5 - 0.8 g, flow rate 2BV/h, adsorbed 3'
      hydroxypuerarin, puerarin and daidzin could be desorbed by alcohol at flow rate
      1BV/h. CONCLUSION: The purity of 3'-hydroxypuerarin, puerarin and daidzin of the
      product obtained from Puerariae Lobatae Radix with optimum technology is 23.39%,
      52.09% and 19.21%, respectively.

PMID- 24134016
TI  - [Study on chemical components in yiqing capsule based on UPLC-ESI-MS-MS and FTIR
      and its anti-inflammatory activity in vitro].
AB  - OBJECTIVE: To study the chemical components in Yiqing capsule by UPLC-ESI-MS-MS
      and its anti-inflammatory activity in vitro. METHODS: The mass spectrometer
      equipped with an eletrospray ion source in positive ion mode was used and data of
      mass spectrum and mass/mass spectrum were analyzed; FTIR was used to detect the
      characteristic spectra of ten bcathes of Yiqing capsule. Compared the spectra by
      principal component analysis and cluster analysis; RAW264.7 cell model induced by
      LPS was established to study the inhibitory effect of Yiqing capsule on the
      release of NO. RESULTS: Totally twelve chemical components were analyzed by the
      established UPLC-ESI-MS-MS method; The results of the principal component
      analysis and the cluster analysis indicated that there were significant
      differences between the sample (batch number: 120703) and other different batches
      of samples; Yiqing capsule could inhibit the release of NO induced by LPS in a
      dose-dependent manner at the concentration of 1 - 100 micromol/L. CONCLUSION:
      UPLC-ESI-MS-MS and FTIR which are rapid, convenient and effective, can be used
      for quality control of Yiping capsule; Yiqing capsule exhibites anti-inflammatory
      activity in vitro.

PMID- 24134017
TI  - [Thinking about the diagnosis and treatment of tuberculosis and the choice of
      operation time for spinal tuberculosis].

PMID- 24134018
TI  - [Analysis of postoperative recurrence reason and observation of reoperation
      outcome for spinal tuberculosis].
AB  - OBJECTIVE: To analyze the reason of postoperative recurrence of spinal
      tuberculosis and observe the clinical outcome of these patients in reoperation.
      METHODS: From January 2002 to May 2010,27 patients with postoperative
      recrudescent spinal tuberculosis were treated. There were 15 males and 12 females
      with an average age of 36.5 years old (ranged, 21 to 65). The risk factors and
      effect strength associated with postoperative recrudescent spinal tuberculosis
      were compared by Logistic regression analysis. Individual operation was performed
      according to the major reason. Re-operative methods including debridment in 5
      cases, debridment and sinuses resection in 7 cases, one stage debridement and
      bone grafting via anterior approach and internal fixation via posterior approach
      in 8 cases, one stage bone grafting and internal fixation via posterior approach
      combined with CT-guided percutaneous catheter drainage and local chemotherapy in
      2 cases, CT-guided percutaneous catheter drainage and local chemotherapy in 5
      cases. Antituberculosis drugs were regularly used in all patients after
      operation. The ESR, X-ray and 3D-CT were regularly performed to estimate the
      progress of tuberculosis and condition of bony fusion. RESULTS: The risk factors
      associated with postoperative recrudescent spinal tuberculosis were complicated,
      including no regularly used antituberculosis drugs before and after operation, no
      early diagnosis and treatment of the postoperative fluidify, malnutrition, no
      thoroughly debridement during operation and poor spinal stability after
      operation, according to effect strength to arrange. There was no injury of blood
      vessel,spinal cord or ureter during reoperation. The follow-up period was from 12
      to 36 months with an average of 24 months. Tuberculosis symptoms disappeared
      after reoperation and no complications such as tuberculosis recurrence, infection
      of incision, sinuses formation and internal fixation failure were found in the
      patients. ESR recovered normal in follow-up and bone graft obtained fusion at 8
      to 12 months after operation and internal fixation position was normal.
      CONCLUSION: The reoperative reasons of spinal tuberculosis are complicated and
      multifactorial. The diagnosis and treatment are difficult. It is important to
      analyze the recrudescent reasons thoroughly before operation,emphasize the
      application of regularly antituberculosis drugs and individual operation,
      meanwhile, reinforce nourishment and supportive treatment.

PMID- 24134019
TI  - [Surgical treatment of thoracic tuberculosis with one stage posterior debridement
      and bone grafting fusion and internal fixation].
AB  - OBJECTIVE: To investigate the effect and indication of one stage posterior
      debridement and bone grafting fusion and internal fixation for thoracic
      tuberculosis. METHODS: From January 2005 to May 2011,12 patients with thoracic
      tuberculosis were treated with one stage posterior debridement and pedicle screw
      fixation combined with regular anti-tuberculosis treatment before and after
      operation. There were 7 males and 5 females,with an average age of 45 years and
      average course of 15 months. Information of operative time, blood loss, bony
      fusion, local kyphosis and neurologic functional were evaluated. RESULTS: All
      infective focus were thoroughly removed and bone graft obtained fusion. The mean
      of operative time and blood loss were 170 min (120-210 min) and 510 ml (200-1 000
      ml),respectively. Cobb angle from (28.7 +/- 9.2) degrees preoperatively decreased
      to (8.2 +/- 3.5) degrees postoperatively(P<0.05). No kyphosis correction
      loss,tubercular recurrence or failure of internal fixation was found. According
      to Frankel grade to evaluate neurological function, all patients arrived to grade
      E. CONCLUSION: One stage posterior debridement and bone grafting fusion and
      internal fixation is an effective method in treating thoracic tuberculosis. It
      has advantages such as thorough debridement, short operative time, less blood
      loss, more kyphosis correction and higher bony fusion rate.

PMID- 24134020
TI  - [One stage anterior debridement, bone fusion and internal fixation for the
      treatment of lumbosacral tuberculosis].
AB  - OBJECTIVE: To explore the clinical effect of the anterior debridement,bone
      fusion, single screw-rod fixation for the treatment of lumbosacral tuberculosis.
      METHODS: From March 2005 to February 2011,18 patients with lumbosacral (L3-S1)
      tuberculosis (including 13 males and 5 females with an average age of 38.5 years
      old ranging from 24 to 61 years) were treated with removing focus completely,
      large piece of iliac bone strut grafting, single screw-rod vertebral lateral
      anterior internal fixation through anterior extraperitoneal approach. The process
      segment was L3,4 in 2 cases, L4,5 in 5, L4 in 2, L5S1 in 6, L4-S1 in 3. All
      patients were routinely treated with antituberculous druy for 12-18 months after
      operation, erythrocyte sedimentation rate and liver function, X-ray films, CT
      examination, were statedly rechecked, and condition of antituberculosis treatment
      and bone grafting fusion were detected. RESULTS: Intraoperative focus were
      exposed clearly, debrided thoroughly. There were no large blood vessels, nerves,
      ureteral injury and other serious complications during operation. All patients
      were followed up form 6 to 42 months with an average of 13 months. Internal
      fixations were not loosening,breaking; bone of grafting was not displacement and
      obtained good healing; erythrocyte sedimentation rate and C-reactive protein were
      normal; tuberculosis lesions were not recurrence. CONCLUSION: Through anterior
      extraperitoneal approach to remove focus, bone fusion, single screw-rod fixation
      in treating lumbosacral tuberculosis can complete cut lesion and rebuild the
      stability of lumbosacral vertebrae,in this area with a single screw and rod
      fixation is a feasible method.

PMID- 24134021
TI  - [Open reduction and mini-plate internal fixation for the treatment of fracture
      and dislocation of coccyx].
AB  - OBJECTIVE: To explore the therapeutic methods of fracture and dislocation of
      coccyx and evaluate its curative effects. METHODS: From May 2002 to March 2010,56
      patients with fracture and dislocation of coccyx were divided into surgical
      treatment group and non-surgical treatment group. There were 7 males and 20
      females in surgical treatment group with an average age of (48.1 +/- 0.6) years
      (ranged, 29 to 62 years), treated with open reduction and mini-plate internal
      fixation. There were 8 males and 21 females in non-surgical treatment group with
      an average age of (47.5 +/- 0.9) years (ranged, 19 to 54 years),treated with
      manipulative reduction. All patients were underwent X-ray examination and were
      finally diagnosed before treatment. Clinical symptoms and Visual Analogue Scales
      (VAS) of all patients were statistically analyzed before and after treatment.
      RESULTS: There was no significant difference between two groups in gender, age,
      BMI index and VAS evaluation. All patients were followed up from 12 to 25 months
      with an average of 17.2 months. In surgical treatment group,there were 26 cases
      with I/a incision and 1 case with II/a incision; the excellent rate of clinical
      symptom was respectively 92.6% and 100% at leaving hospital and final follow-up;
      the improvement rate of VAS was 97.6% and was excellent result;internal fixtures
      were removed at the 1 to 2 years after treatment and no unwell symptoms occurred;
      VAS of all patients in the group was 0 point. In non-surgical treatment group,the
      excellent rate of clinical symptom was respectively 72.4% and 82.8% at leaving
      hospital and final follow-up; the improvement rate of VAS was 72.1% and was good
      result. There was significant difference in clinical results between two groups
      (P<0.05). CONCLUSION: The results indicated that fracture and dislocation of
      coccyx should be treated in time. For the treatment of patients with manipulative
      reduction failures, instability reduction by X-ray examination and serious rectal
      irritation, open reduction and mini-plate internal fixation can obtain
      satisfactory results.

PMID- 24134022
TI  - [Comparison of diagnostic value between DR and MSCT in fracture and dislocation
      of foot and ankle].
AB  - OBJECTIVE: To compare the diagnostic value between digital photography (DR) and
      multi-slice spiral CT (MSCT) in fracture and dislocation of foot and ankle.
      METHODS: From August 2010 to August 2012, the DR and MSCT data of 52 patients
      with fracture and dislocation of foot and ankle were compared according to
      results of surgery or discharge diagnosis. There were 37 males and 15 females,
      aged from 15 to 49 years old. Wilcoxon signed rank test was used for statistical
      analysis. RESULTS: The results of 52 cases of MSCT were matched with the
      postoperative or discharge diagnosis. A total of 172 fractures were found on MSCT
      and 98 fractures were found on DR, the results had significant difference in
      detecting fracture (V=1 081, P<0.05); A total of 24 dislocations were found on
      MSCT and 16 dislocations were found on DR,the results also had significant
      difference in detecting dislocation (V=21, P<0.05). Fractures of 6 cases with DR
      diagnosis were corrected and located by MSCT. CONCLUSION: MSCT is significantly
      better than DR in diagnosis of fracture and dislocation of foot and ankle. The
      examination of two parts should be performed in DR. MSCT and multi-planar
      reconstruction (MPR) examination should be further performed if DR results are
      unclear or do not match with clinical symptoms, missed diagnosis and misdiagnosis
      can be avoided.

PMID- 24134023
TI  - [Study on the correlation between "Gucuofeng and Jinchucao" and cervical
      spondylosis].
AB  - OBJECTIVE: To explore the relation between "Gucuofeng and Jinchucao" and cervical
      spondylosis. METHODS: From March 2006 to October 2011,333 patients with cervical
      spondylosis were collected in the study as cervical spondylosis group; 30
      subjects of control group come from student of Shuguang Hospital and other health
      volunteer. There were 119 males and 214 females with a mean age of (48.11 +/-
      12.21) years in cervical spondylosis group and there were 6 males and 24 females
      with a mean age of (45.27 +/- 10.12) years in control group. In aspect of the
      symptom and sign, dynamic palpation, X-ray examination wer performed to find the
      incidence rate of "Gucuofeng and Jinchucao" in two groups. RESULTS: There was
      significant difference in symptom and sign, dynamic palpation, X-ray examination
      between two groups (P<0.01). In cervical spondylosis group, "Gucuofeng and
      Jinchucao" occurred in 293 cases (87.99%),there was significant difference
      compared with control group (P<0.01). CONCLUSION: Cervical "Gucuofeng and
      Jinchucao" is one of pathological point of cervical spondylosis,and it can
      provide a guidance for the diagnosis and treatment of cervical spondylosis.

PMID- 24134024
TI  - [Comparison of early clinical effects of two hip prosthesis designs between
      ceramics to ceramics and metal to polyethylene].
AB  - OBJECTIVE: To retrospectively study early therapeutic effects of the ceramics to
      ceramics prosthesis design in treating hip disease. METHODS: From October 2007 to
      September 2010, 42 patients (44 hips) with hip disease underwent replacement of
      total hip. Hip prosthesis designs included the Pinnacle ceramics to ceramics and
      the Duraloc metal to polyethylene,produced by DePuy Company, all were non-bone
      cement type of artificial hip joint. Twenty patients (22 hips) were performed
      with ceramics to ceramics total hip prosthesis (CoC group, there were 12 males
      and 8 females, aged from 21 to 49 years) and 22 patients (22 hips) were performed
      with metal to polyethylene total hip prosthesis (MoP group, there were 13 males
      and 9 females, aged from 42 to 55 years). All the surgical approachs were
      posterolateral, and the routine anticoagulation and the corresponding functional
      exercise were performed after operation. The follow-up time was 6 months at least
      including clinical and radiographic observation. Measured the motion of joint and
      evaluated the function of hip joint according to Harris classification. RESULTS:
      All clinical effects were satisfactory and no dislocation ,loosening,infection,
      deep venous thrombosis and other complications occurred. There was no statistical
      significance in Harris scoring and the motion of joint between two groups before
      and after operation (P>0.05). CONCLUSION: The clinical effect of ceramics to
      ceramics prosthesis design in improving clinical symptoms and the motion of joint
      is coordinate with metal to polyethylene total hip prosthesis, however, its
      advantages and long-term efficacy need further observing. The ceramics to
      ceramics prosthesis design may be a good choice for the young patients with hip
      disease because of its good wear resistance.

PMID- 24134025
TI  - [Case-control study on double screws system and compressed three canulated screws
      in treating femoral neck fractures].
AB  - OBJECTIVE: To compare the clinical effects of double screws system and compressed
      three canulated screws in treating femoral neck fractures. METHODS: From January
      2007 to June 2009, the clinical data of 67 patients with femoral neck fractures
      underwent operation were retrospectively analyzed. There were 38 males and 29
      females,aged from 31 to 71 years with an average of 50.6 years, left was in 41
      cases and right was in 26 cases. The patients were divided into two groups (group
      A and B) based on the different fixation method. Of them, 30 cases (group A,19
      males and 11 females) were treated with double screws system and 37 cases (group
      B, 19 males and 18 females) with compressed three canulated screws. In group A,
      Pauwells angle was more than or equal 50 degrees in 16 cases and Pauwells angle
      less 50 degrees in 14 cases; in group B, Pauwells angle was more than or equal 50
      degrees in 22 cases and Pauwells angle less 50 degrees in 15 cases. Duration of
      hospitalization, operative time, intraoperative blood loss, postoperative time in
      bed, infection of incision, postoperative complication, quality of fracture
      reduction, position of internal fixation, incidence of non-union and femoral head
      necrosis, incidence of failure fixation, joint function (Harris score) were
      compared between two groups. RESULTS: All patients were followed up from 30 to 59
      months with an average of 42 months. There was no significant differences in
      aspect of duration of hospitalization, infection of incision, intraoperative
      blood loss, walking time, postoperative complications between two groups(P>0.05).
      Operative time of group A [(31.1 +/- 9.7) min]was less than that of group B
      [(40.4 +/- 12.7) min] (P<0.05). There was no significant differences in quality
      of fracture reduction, position of internal fixation, incidence of non-union and
      femoral head necrosis between two groups (P>0.05). In the patients with Pauwells
      angle more than or equal 50 degrees in group A, there was no retreated screws,
      broken screws, screw cut-off from the femoral head;a head;and in group B,
      retreated screws occurred in 2 cases, screw cut-off from the femoral head
      occurred in 2 cases, screws not completely getting in femoral head occurred in 2
      cases; there was significant differences between two groups (P<0.05). The
      patients with Pauwells angle less 50 degrees in group A, screw loosening occurred
      in one case; and in group B, screw retreating occurred in one cases; there was no
      significant differences between two groups (P>0.05). All patients who suffered
      from screw loosening, retreating or cut-off from the femoral head were more than
      65 years old. There was no significant differences in the joint function between
      two groups at 6 and 30 months after operations (P>0.05). CONCLUSION: Double
      screws system has advantages of minimal invasion, easy operation, reliable
      fixation in treatment of femoral neck fractures. Compared with the traditional
      compressed three canulated screws,double screws system has less fixation failure
      rate and higher hip function scoring. It has a good clinical effect especially
      for the patients with Pauwells angle more than or equal 50 degrees.

PMID- 24134026
TI  - [Surgical strategy for upper cervical vertebrae instability through the anterior
      approach].
AB  - OBJECTIVE: To explore the choice and effect of internal fixation in treating
      upper cervical vertebrae instability through anterior approach. METHODS: From
      March 2000 to September 2010,83 patients with upper cervical vertebrae
      instability were treated with internal fixation through anterior approach. There
      were 59 males and 24 females with a mean age of 42 years old (ranged, 20 to 68).
      Among these patients, 36 patients were treated with odontoid screw fixation, 16
      patients with C1,2 transarticular screw fixation, 23 patients with C2,3 steel
      plate fixation, 5 patients with odontoid screw and transarticular screw
      fixation,2 patients with odontoid screw and C2.3 steel plate fixation, 1 patient
      with C1,2 transarticular screw and C2,3 steel plate fixation. RESULTS: One
      patient with completely cervical vertebrae cord injury died of pulmonary
      infection after C1,2 transarticular screw fixation. Other patients were followed
      up from 8 to 36 months with an average of 15 months. Upper cervical vertebrae
      stability were restored without vertebral artery and spinal cord injury. Thirty
      six patients were treated with odontoid screw fixation and 5 patients were
      treated with screw combined with transarticular screw fixation obtained bone
      union in the dentations without bone graft. Among the 16 patients treated with
      C1,2 transarticular screw fixation, 13 patients obtained bone union after bone
      graft; 1 patient died of pulmonary infection after surgery; 1 patient with
      comminuted odontoid fracture of type II C and atlantoaxial anterior dislocation
      did not obtain bone union after bone graft,but the fibrous healing was strong
      enough to maintain the atlantoaixal joint stability; 1 patient with obsolete
      atlantoaxial anterior dislocation were re-treated with Brooks stainless steel
      wire fixation and bone graft through posterior approach, and finally obtained
      bone union. CONCLUSION: It could obtain satisfactory effects depending on the
      difference of cervical vertebrae instability to choose the correctly surgical
      method.

PMID- 24134027
TI  - [Resorption phenomenon of intervertebral disc herniations by conservative
      treatment: a case report].

PMID- 24134028
TI  - [Relationship between effect of sacral canal injection and different sections,
      types, courses of lumbar intervertebral disc herniation].
AB  - OBJECTIVE: To observe the effects of sacral canal injection in treating lumbar
      intervertebral disc herniation with different sections, types and courses, in
      order to provide selective basis for clinical indications. METHODS: From March
      2007 to May 2011, 329 patients with lumbar intervertebral disc herniation were
      treated with sacral canal injection and their data were retrospectively analyzed.
      There were 178 males and 151 females,ranging in age from 16 to 78 years old with
      an average of 45 years; ranging in course of disease from 2 days to 41 years with
      an average of 4.1 years. All the protrusions were simple segment, and L3,4 of 51
      cases, L4,5 of 142 cases, L5S1 of 136 cases including central protrusion of 137
      cases, posterolateral of 145 cases, extreme posterolateral of 47 cases. According
      to different sections, types, courses (more than or less than 6 months ) of
      lumbar intervertebral disc herniation, the patients were divided into several
      groups, clinical effects of the groups were compared and analyzed. RESULTS:
      Clinical effect of protrusion in L5S1 group was better than that of L3,4, L4,5
      group; the effect of patients with course less than 6 months was better than with
      course more than 6 months; effect of posterolateral protrution was better than
      that of central and extreme posterolateral protrusion. Clinical effect of
      corresponding the three conditions was better than that of others no
      corresponding the three conditions,the three conditions included the course less
      than 6 months, protrusion in L5S1 section, with type of posterolateral
      protrusion. No complications were found in all patients and cured patients were
      followed up for 1 year with the recurrence rate of 0.05%. CONCLUSION: The
      patients with short course, lower protrusion, type of posterolateral protrusion
      can obtained better effects, while the patients who meets the three conditions is
      appropriate mostly to sacral canal injection therapy.

PMID- 24134029
TI  - [Evaluation of early clinical results of two stage hip replacement after failed
      internal fixation for femoral neck fractures].
AB  - OBJECTIVE: To evaluate the early clinical results of two stage hip replacement
      after failed internal fixation for femoral neck fractures in young patients.
      METHODS: From June 2008 to June 2010,24 patients with femoral head necrosis
      caused by failed internal fixation were treated with hip arthroplasty. Among
      them, 12 patients were male and 12 patients were female, with an average age of
      42.9 years old (ranged, 18 to 58). According to Harris score and X-ray
      examination, the clinical result was evaluated. RESULTS: Twenty-three cases were
      followed up with an average age of 34.4 months (ranged, 25 to 48). After
      operation, 1 case complicated with the dislocation of hip joint. No deep
      infection of hip joint, prosthetic loosing or peripheral fracture was found. The
      mean Harris score was 90.9 +/- 4.3, and 18 obtained excellent results, 4 good and
      1 fair. CONCLUSION: Although treatment of femoral head necrosis with two stage
      hip replacement after failed internal fixation is difficult during operation, its
      early result is satisfactory.

PMID- 24134030
TI  - [Transpedicular bone graft for the treatment of thoracolumbar vertebral fractures
      through Wiltse approach].
AB  - OBJECTIVE: To explore methods and therapeutic effects of transpedicular bone
      graft in treating thoracolumbar fractures through Wiltse approach. METHODS: From
      March 2009 to February 2012,56 patients with thoracolumbar fractures were treated
      by transpedicular bone graft through Wiltse approach. Among them, there were 36
      males and 20 females, ranging in age from 14 to 55 years old (mean, 41 years
      old). The time from injury to operation from 2 to 15 d (mean,3 d). Twenty-five
      cases were caused by falling down, 7 cases were caused by slipping, 20 cases were
      caused by car accident and 4 cases were caused by crush trauma. MRI was performed
      before operation to exclude pathological fracture. The distance between
      multifidus muscle and longissimus to midcourt line was measured. Self-made trocar
      was applied in operation. According to AO classification,there were 33 cases with
      type A1 compression fracture,5 cases with type A2 cleavage fracture and 18 cases
      with type A3 burst fracture. Sixteen cases of the 56 cases combined with spinal
      cord injury. Based on Frankel neurologic grading system, preoperative
      neurological function was grade B in 5 cases, grade C in 2 cases, gade D in 9
      cases. Preoperative Denis gading were P5. Frankel and lumbago Denis clssification
      were used to evaluate neurological function and lumbago. The imaging data before,
      after operation and the latest follow-up were used to evaluate correction vision.
      RESULTS: All patients were followed up over 24 months. At the time of the latest
      follow-up, Frankel B were 3 cases, Frankel C were 2 cases, Frankel D were 4 cases
      and Frankel E were 7 cases. According to lumbago Denis clssification, P1
      (painlessness) were 32 cases, P2 ( slight pain without treatment) were 18 cases,
      P3 ( moderate pain and taking medicine occasionally) were 6 cases. The anterior
      vertebral height improved from preoperative (13.38 +/- 4.72)mm to postoperative
      (22.18 +/- 1.44)mm. The Cobb's angle decreased from preoperative (28.39 +/- 2.64)
      degrees to (10.07 +/- 3.05) degrees. There were no nails broken, rod broken,
      internal fixation lossen and vertebral body recompression. CONCLUSION:
      Transpedicular bone graft for thoracolumbar fractures through Wiltse approach can
      reduce intraoperative blood loss and postoperative complications, and aviod
      "eggshell" vertebral body. Mastering revealed way, drafting detailed preoperative
      plan and eariler exercise is the key to the success of treatment.

PMID- 24134031
TI  - [Effects of promoting blood circulation to remove meridian obstruction combined
      with medicinal guides on related osteogenesis factors in rabbits with femoral
      head necrosis].
AB  - OBJECTIVE: To observe effects of blood circulation promoting compounds combined
      with medicinal guides on content of bone glaprotein (BGP), bone morphogenetic
      protein-2 (BPM-2) and expression of BMP-2 mRNA in rabbits with femoral head
      necrosis, and explore its mechanism. METHODS: Ninety-eight healthy Spragur-Dawley
      male rabbits were collected and weighted 2.2 to 2.8 kg. Eighty-four rabbits were
      built femoral head necrosis model by freezing left femoral head in liquid
      nitrogen, then randomly divided into 6 groups, 14 in each group. The 6 groups
      included model group,promoting blood circulation to remove meridian obstruction
      group,promoting blood circulation to remove meridian obstruction combined with
      achyranthes bidentata group,radix angelicae pubescentis, asarum group, and
      platycodon grandiflorum group,other 14 rabbits were sham operation group. While
      drug groups were administrated corresponding Chinese herb after molding,model
      group and shamp operation group were given saline. Recombinant human granulocyte
      colony stimulating factor ( 30 microg x kg(-1) x d(-1))were injected into all
      rabbits for 7 days. Samples were taken on the second and fourth week,the content
      of BGP and BMP-2 were detected by enzyme-linked immunosorbent assay (ELSA) and
      radioimmunoassay (RIA), histopathological changes of left femoral head were
      observed by Hematoxylin and Eeosin staining (HE), and expression of BMP-2 mRNA
      were tested by fluorescence in situ hybridization. RESULTS: Compared with sham
      operation group, the rate of empty lacunae femoral head were obviously increased
      in model group, and the content of BGP were increased on the second week, and BMP
      2 and BMP-2 mRNA were decreased on the fourth week. Compared with model group,
      the content of BGP, BMP-2 and BMP-2 mRNA were higher both of the second and
      fourth week in promoting blood circulation to remove meridian obstruction group.
      The rate of empty la- cunae femoral head were lower in achyranthes bidentata
      group, BGP, BMP-2 and BMP-2 mRNA were higher on the fourth week. The rate of
      empty lacunae femoral head were lower in platycodon grandiflorum group, and BGP
      were decreased on the second and fourth week, BMP-2 were lower on the second week
      ,while BMP-2 mRNA were decreased on the fourth week; the content of BMP-2 and BMP
      2 mRNA were increased in radix angelicae pubescentis group on the second week;
      while there was no change in asarum group. CONCLUSION: Radix angelicae
      pubescentis can increase the content of BGP, BMP-2 and expression of BMP-2 mRNA
      ,which is an effective mechanism of preventing femoral head necrosis.

PMID- 24134033
TI  - [Treatment of comminuted fracture of tibial plateau with ni-ti shape memory alloy
      bow-teeth screws combined with locking plate internal fixation].
AB  - OBJECTIVE: To assess the clinical effects of Ni-Ti shape memory alloy bow-teeth
      screws combined with locking plate internal fixation in treating comminuted
      fracture of tibial plateau. METHODS: From January 2003 to December 2008, 17
      patients with comminuted fracture of tibial plateau were treated with Ni-Ti shape
      memory alloy bow-teeth screws and locking plate internal fixation. There were 9
      males and 8 females with an average age of 33.7 years old (ranged, 23 to 48
      years). All fractures were fresh and injured time less 3 weeks and 2 patients
      with common peroneal nerve injury. According to Schatzker typing, type V was in 1
      case and type VI was in 16 cases. RESULTS: All patients were followed up from 10
      to 22 months with an average of 18 months and all incisions healed in one stage.
      At 3 to 12 weeks after operation, knee joint function of 16 cases arrived to the
      level of uninjured side and 1 case was poor in flexed function. All fractures
      obtained union at 3 to 5 months after operation, and internal fixtures were
      removed at 1 year after operation and no reduction lossing or refracture
      occurred. At final follow-up, no bone block shifting, internal fixture loosening
      and breakage was found. According to the standard of Xushanding's knee joint
      function, 9 cases got excellent results, 4 good, 4 fair. CONCLUSION: The design
      of Ni-Ti shape memory alloy bow-teeth screws is adapt to irregular anatomic
      structure of comminuted fractures of tibial plateau,it can continuously
      pressurize and promote bone healing. Multi drop lockedup may avoid wide-ranging
      stripping local soft tissue, and form three-dimension fixation after combined
      with locking plate internal fixation, can effective recover anatomic structure of
      fracture. So Ni-Ti shape memory alloy bow-teeth screws combined with locking
      plate internal fixation is an effective method in treating comminuted fracture of
      tibial plateau.

PMID- 24134032
TI  - [Gene expression of bone mesenchymal stem cells transduced by the lentiviral
      vector of SOX9 gene].
AB  - OBJECTIVE: To construct one lentiviral vector containing mouse SRY-related high
      mobility group-box gene 9 (SOX9) and transfect the murine bone mesenchymal stem
      cells (mBMSCs) in vitro and observe the expression of target gene. METHODS: RNA
      from the vectors containing mouse SOX9 gene were extracted and SOX9 genes were
      amplified by reverse transcription-Polymerase Chain Reaction (RT-PCR). The SOX9
      genes were connected into lentiviral vectors pGC-FU. Then pGC-FU-SOX9 transduced
      into 293T cells to produce recombinant lentivirus called as Lenti-SOX9-EGFP.
      mBMSCs were transfected. The expression of target gene was detected by
      immunofluorescence, RT-PCR and Western Blot. RESULTS: Lenti-SOX9-EGFP was
      recombined successfully and transduced efficiently into mBMSCs. The expression of
      SOX9 gene was confirmed by RT-PCR and Western Blot. CONCLUSION: Lentiviral vector
      of mouse SOX9 gene can transfect successfully into mBMSCs. Meanwhile, SOX9 gene
      may be expressed in mBMSCs. This will provide the target cells for the following
      study about SOX9 gene repairing cartilage injury.

PMID- 24134034
TI  - [Treatment of children with femoral subtrochanteric fracture with advanced
      elastic intramedullary nail technology].
AB  - OBJECTIVE: To explore curative effects of advanced elastic intramedullary nail
      technology in treating children with femoral subtrochanteric fracture. METHODS:
      Form March 2009 to December 2010, 16 children with femoral subtrochanteric
      fracture were treated with advanced elastic intramedullary nail technology. There
      were 12 males and 4 females ranging in age from 7 to 15 years old with a mean of
      9.8 years old. According to fracture classification, 9 cases were stable
      fractures (traverse or short oblique type) and 7 cases were unstable fractures
      (comminuted or long oblique type). Radiographs and complications were
      retrospectively reviewed. Fracture healing were evaluated according to Flynn
      criteria. RESULTS: All children were followed up from 11 to 32 months with an
      average of 21 months. No incision infecton,bone nonunion and breakage of screw
      occurred. The fracture healing time was from 8 to 16 weeks with an average of
      10.1 weeks. According to Flynn criteria, 14 cases got excellent results, 1
      moderate and 1 poor. CONCLUSION: Advanced elastic intramedullary nail technology
      for the treatment of children with femoral subtrochanteric fracture is a safe and
      effective fixation, which is good for early mobilization, shorter the duration of
      hospital stays and reduce complications.

PMID- 24134035
TI  - [Treatment of fracture of fifth metatarsal base and degree III lateral ligament
      injury of ankle with compressed cannulated screw and suture anchors].
AB  - OBJECTIVE: To investigate the clinical outcomes of surgical treatment of fracture
      of the fifth metatarsal base combined with degree III lateral ligament injury of
      ankle. METHODS: From January 2008 to December 2011, 32 patients with fracture of
      the fifth metatarsal base combined with degree III lateral ligament injury of
      ankle were treated with surgery. Fractures were fixed with compressed canulated
      screw and ligaments were repaired with suture anchors. After operation, ankle
      joints were fixed in neutral position and slightly valgus position by plaster
      slab. Taking out stitch was performed at 2 weeks after operation and non-weight
      loading walking by double crutches support started; after the 6 weeks, remove the
      gypsum and part-weight loading walking by brace protection; at the 8 weeks after
      operation, completely weight loading walking was permitted. American Orthopaedic
      Foot and Ankle Society (AOFAS) was used to evaluate the clinical effect. RESULTS:
      Thirty-two patients were followed up from 8 to 18 months with an average of 12
      months. All fractures obtained healing with an average time of 12.5 weeks
      (ranged, 8 to 24 weeks). According to the standard of AOFAS, 18 cases got
      excellent results and 14 good. CONCLUSION: The method that fracture fixation with
      compressed canulated screw and ligament repair with suture anchors can obtain
      satisfactory effects in treating fracture of the fifth metatarsal base and degree
      III lateral ligament injury of ankle.

PMID- 24134036
TI  - [Comminuted fracture of distal humerus by arm wrestling: a case report].

PMID- 24134037
TI  - [Progress on Wnt/beta-catenin signal pathway regulating the cartilage metabolism
      in osteonecrosis].
AB  - More and more scholars agreed with the viewpoint that osteonecrosis relates with
      the metabolic activity of chondrocyte. Moreover,the activation of beta-catenin
      among Wnt/beta-catenin signal pathway can promote differentiation of chondrocyte
      and can promote differentiated cell death. So it suggests that this signal
      pathway should have an effect to occurrence and development of osteonecrosis by
      regulating the metabolic activity of chondrocyte. Through the establishment of
      conditional beta-catenin knockout mice,it is helpful to understand the
      pathogenesis of Wnt/beta-catenin signal pathway regulating cartilage metabolism.
      By the way we can understand the pathogenesis of osteonecrosis and give a
      targeted treatment to the disease. This article reviewed the relationship of
      three aspects of Wnt/beta-catenin signal pathway, cartilage metabolism and
      osteonecrosis.

PMID- 24134038
TI  - [Progress on tantalum rod implanting for the treatment of femur head necrosis].
AB  - Incorrect treatment for femur head necrosis can cause collapse of femoral head
      and tresult in severe harm for the patients (especially for the patient with
      middle-aged and young). The structure and mechanics characteristics of tantalum
      rod is similar to bone tissue, it higher strength and can adapt the internal
      environment of organism, so it has a large potency in treating femur head
      necrosis. Treatment of early femur head necrosis with tantalum rod implanting had
      alreadly widey applied at home and abroad, the method has the advantages of
      simple operation, little risk, less complication and beseems the patient with
      stage I - II of ARCO. But reasons that the difficult diagnosis of early femur
      head necrosis, localized effect of tantalum rod, different experience of medical
      worker,caused the contentions about effect of tantalum rod implanting. With
      development of science, tantalum rod implanting combined with correlative
      biotechnology should raise the effect in treating femur head necrosis.

PMID- 24134039
TI  - Design, synthesis and biological assessment of a triazine dendrimer with
      approximately 16 Paclitaxel groups and 8 PEG groups.
AB  - The synthesis and characterization of a generation three triazine dendrimer that
      displays a phenolic group at the core for labeling, up to eight 5 kDa PEG chains
      for solubility, and 16 paclitaxel groups is described. Three different diamine
      linkers--dipiperidine trismethylene, piperazine, and aminomethylpiperidine--were
      used within the dendrimer. To generate the desired stoichiometric ratio of 8 PEG
      chains to 16 paclitaxel groups, a monochlorotriazine was prepared with two
      paclitaxel groups attached through their 2'-hydroxyls using a linker containing a
      labile disulfide. This monochlorotriazine was linked to a dichlorotriazine with
      aminomethylpiperidine. The resulting dichlorotriazine bearing two paclitaxel
      groups could be reacted with the eight amines of the dendrimer. NMR and MALDI-TOF
      confirm successful reaction. The eight monochlorotriazines of the resulting
      material are used as the site for PEGylation affording the desired 2:1
      stoichiometry. The target and intermediates were amenable to characterization by
      (1)H and (13)C NMR, and mass spectrometry. Analysis revealed that 16 paclitaxel
      groups were installed along with 5-8 PEG chains. The final construct is 63% PEG,
      22% paclitaxel, and 15% triazine dendrimer. Consistent with previous efforts and
      computational models, 5 kDa PEG groups were essential for making the target water
      soluble. Molecular dynamics simulations showed a high degree of hydration of the
      core, and a radius of gyration of 2.8 +/- 0.2 nm. The hydrodynamic radius of the
      target was found to be 15.8 nm by dynamic light scattering, an observation
      indicative of aggregation. Drug release studies performed in plasma showed slow
      and identical release in mouse and rat plasma (8%, respectively). SPECT/CT
      imaging was used to follow biodistribution and tumor uptake. Using a two
      component model, the elimination and distribution half-lives were 2.65 h and 38.2
      h, respectively. Compared with previous constructs, this dendrimer persists in
      the vasculature longer (17.33 +/- 0.88% ID/g at 48 h postinjection), and showed
      higher tumor uptake. Low levels of dendrimer were observed in lung, liver, and
      spleen (~6% ID/g). Tumor saturation studies of small prostate cancer tumors (PC3)
      suggest that saturation occurs at a dose between 23.2 mg/kg and 70.9 mg/kg.

PMID- 24134040
TI  - P3F9(2-): an all-pseudo-pi* 2pi-aromatic.
AB  - A qualitative MO analysis suggests (PH3)3(2-) as a candidate for an all-pseudo
      pi* 2pi-aromatic; however computational studies rule out its existence. Fluorine
      substitution which increases the contribution of p orbitals on P in the pseudo
      pi* MO makes (PF3)3(2-) a minimum and an aromatic. The 2pi aromaticity arising
      from the bonding combination of the three pseudo-pi* fragment MOs is comparable
      to that in C3O3(2-) and is another example for the analogy between CO and PF3.
      The dianion (PF3)3(2-) forms the first example of a three-membered ring with all
      the vertices constituted by pentacoordinate phosphorus. The ability of PF3 to
      form the all-pseudo-pi* 2pi-aromatic system is not shared by the heavier
      analogues, AsF3 and SbF3. 

PMID- 24134043
TI  - Frailty as a terminal illness.

PMID- 24134041
TI  - Near-infrared fluorescence energy transfer imaging of nanoparticle accumulation
      and dissociation kinetics in tumor-bearing mice.
AB  - In the current study we show the dissociation and tumor accumulation dynamics of
      dual-labeled near-infrared quantum dot core self-assembled lipidic nanoparticles
      (SALNPs) in a mouse model upon intravenous administration. Using advanced in vivo
      fluorescence energy transfer imaging techniques, we observed swift exchange with
      plasma protein components in the blood and progressive SALNP dissociation and
      subsequent trafficking of individual SALNP components following tumor
      accumulation. Our results suggest that upon intravenous administration SALNPs
      quickly transform, which may affect their functionality. The presented technology
      provides a modular in vivo tool to visualize SALNP behavior in real time and may
      contribute to improving the therapeutic outcome or molecular imaging signature of
      SALNPs. 

PMID- 24134044
TI  - Evaluation of nausea and vomiting: a case-based approach.
AB  - In the absence of acute abdominal pain, significant headache, or recent
      initiation of certain medications, acute nausea and vomiting is usually the
      result of self-limited gastrointestinal infections. Nausea and vomiting is also a
      common adverse effect of radiation therapy, chemotherapy, and surgical
      anesthesia. Other potential diagnoses include endocrine conditions (including
      pregnancy), central nervous system disorders, psychiatric causes, toxin exposure,
      metabolic abnormalities, and obstructive or functional gastrointestinal causes.
      The likely cause of acute nausea and vomiting can usually be determined by
      history and physical examination. Alarm signs such as dehydration, acidosis
      caused by an underlying metabolic disorder, or an acute abdomen warrant
      additional evaluation. Based on the suspected diagnosis, basic laboratory testing
      may include urinalysis, urine pregnancy testing, complete blood count,
      comprehensive metabolic panel, amylase and lipase levels, thyroid-stimulating
      hormone level, and stool studies with cultures. Imaging studies include abdominal
      radiography, ultrasonography, and computed tomography. Computed tomography of the
      head should be performed if an acute intracranial process is suspected. Chronic
      nausea and vomiting is defined by symptoms that persist for at least one month.
      Patients with risk factors for gastric malignancies or alarm symptoms should be
      evaluated with esophagogastroduodenoscopy. If gastroparesis is suspected, a
      gastric emptying study is recommended. In addition to functional causes, it is
      also important to consider psychiatric causes when evaluating patients with
      chronic nausea and vomiting. 

PMID- 24134045
TI  - Top 20 research studies of 2012 for primary care physicians.
AB  - This is the second annual summary of top research studies in primary care. In
      2012, through regular surveillance of more than 100 English-language clinical
      research journals, seven clinicians identified 270 studies with the potential to
      change primary care practice, called POEMs, or patient-oriented evidence that
      matters. These studies were then summarized in brief, structured critical
      appraisals and e-mailed to subscribers, including members of the Canadian Medical
      Association. A validated tool was used to obtain feedback from these physicians
      about the clinical relevance of each POEM and the benefits the physicians
      expected for their practice. The 20 identified research studies rated as most
      relevant cover common topics such as diabetes mellitus, cardiovascular disease
      prevention, infectious disease, musculoskeletal disease and exercise, cancer
      screening, and women's health. 

PMID- 24134047
TI  - A team approach: comprehensive evaluation for functional decline in older
      patients.

PMID- 24134046
TI  - Functional decline in older adults.
AB  - Functional disability is common in older adults. It is often episodic and is
      associated with a high risk of subsequent health decline. The severity of
      disability is determined by physical impairments caused by underlying medical
      conditions, and by external factors such as social support, financial support,
      and the environment. When multiple health conditions are present, they often
      result in greater disability than expected because the patient's ability to
      compensate for one problem may be affected by comorbid conditions. Evaluation of
      functional disability is most effective when the physician determines the course
      of the disability, associated symptoms, effects on specific activities, and
      coping mechanisms the patient uses to compensate for the functional problem.
      Underlying health conditions, impairments, and contextual factors (e.g.,
      finances, social support) should be identified using validated screening tools.
      Interventions should focus on increasing the patient's capacity to cope with task
      demands and reducing the demands of the task itself. Interventions for functional
      decline in older adults are almost always multifactorial because they must
      address multiple conditions, impairments, and contextual factors. 

PMID- 24134048
TI  - FPIN's clinical inquiries: Management of ADHD in preschool-aged children.

PMID- 24134049
TI  - Bilateral papulosquamous lesions.

PMID- 24134052
TI  - Comparison of membrane insertion pathways of the apoptotic regulator Bcl-xL and
      the diphtheria toxin translocation domain.
AB  - The diphtheria toxin translocation domain (T-domain) and the apoptotic repressor
      Bcl-xL are membrane proteins that adopt their final topology by switching folds
      from a water-soluble to a membrane-inserted state. While the exact molecular
      mechanisms of this transition are not clearly understood in either case, the
      similarity in the structures of soluble states of the T-domain and Bcl-xL led to
      the suggestion that their membrane insertion pathways will be similar, as well.
      Previously, we have applied an array of spectroscopic methods to characterize the
      pH-triggered refolding and membrane insertion of the diphtheria toxin T-domain.
      Here, we use the same set of methods to describe the membrane insertion pathway
      of Bcl-xL, which allows us to make a direct comparison between both systems with
      respect to the thermodynamic stability in solution, pH-dependent membrane
      association, and transmembrane insertion. Thermal denaturation measured by
      circular dichroism indicates that, unlike the T-domain, Bcl-xL does not undergo a
      pH-dependent destabilization of the structure. Forster resonance energy transfer
      measurements demonstrate that Bcl-xL undergoes reversible membrane association
      modulated by the presence of anionic lipids, suggesting that formation of the
      membrane-competent form occurs close to the membrane interface. Membrane
      insertion of the main hydrophobic helical hairpin of Bcl-xL, alpha5-alpha6, was
      studied by site-selective attachment of environment-sensitive dye NBD. In
      contrast to the insertion of the corresponding TH8-TH9 hairpin into the T-domain,
      insertion of alpha5-alpha6 was found not to depend strongly on the presence of
      anionic lipids. Taken together, our results indicate that while Bcl-xL and the T
      domain share structural similarities, their modes of conformational switching and
      membrane insertion pathways are distinctly different. 

PMID- 24134053
TI  - HIV and depression in Eastern Nigeria: the role of HIV-related stigma.
AB  - To examine the prevalence of depression among HIV-positive patients in Eastern
      Nigeria and to explore its association with HIV-related stigma. One hundred and
      five patients with a diagnosis of HIV attending HIV clinics in Eastern Nigeria
      completed a questionnaire consisting of demographic and health background, the
      Patients Health Questionnaire (to measure depression) and the Berger HIV stigma
      scale. As many as 33.3% of participants were considered depressed. Depression was
      positively correlated with overall stigma score with further analysis finding a
      positive correlation with all four subscales of the questionnaire (personalised
      stigma, disclosure, negative self-image and public attitudes). Individuals
      experiencing more side effects of HIV treatment were also rated as more
      depressed. A regression analysis found that negative self-image and number of
      treatment side effects were significant predictors of depression. Depression is
      positively associated with HIV-related stigma in this sample in Eastern Nigeria.
      As both stigma and depression have been shown to have a negative impact on
      quality of life for those with HIV, health professionals working to support them
      should be aware of the impact of stigma on risk of depression. Screening for both
      HIV-related stigma and depression would be an important intervention to promote
      both physical and psychological well-being amongst HIV-positive patients in
      Eastern Nigeria. 

PMID- 24134054
TI  - Development and application of a multi-axis dynamometer for measuring grip force.
AB  - OBJECTIVE: This paper describes the development and application of a novel multi
      axis hand dynamometer for quantifying 2D grip force magnitude and direction in
      the flexion-extension plane of the fingers. METHODS: A three-beam reconfigurable
      form dynamometer, containing two active beams for measuring orthogonal forces and
      moments regardless of point of force application, was designed, fabricated and
      tested. Maximum grip exertions were evaluated for 16 subjects gripping
      cylindrical handles varying in diameter. RESULTS: Mean grip force magnitudes were
      231 N (SD = 67.7 N), 236 N (72.9 N), 208 N (72.5 N) and 158 N (45.7 N) for 3.81
      cm, 5.08 cm, 6.35 cm and 7.62 cm diameter handles, respectively. Grip force
      direction rotated clockwise and the centre of pressure moved upward along the
      handle as handle diameter increased. CONCLUSIONS: Given that the multi-axis
      dynamometer simultaneously measures planar grip force magnitude and direction,
      and centre of pressure along the handle, this novel sensor design provides more
      grip force characteristics than current sensor designs that would improve
      evaluation of grip characteristics and model-driven calculations of
      musculoskeletal forces from dynamometer data.

PMID- 24134055
TI  - Reinvestigation of the elementary chemical kinetics of the reaction C2H5(*) + HBr
      (HI) -> C2H6 + Br(*) (I(*)) in the range 293-623 K and its implication on the
      thermochemical parameters of C2H5(*) free radical.
AB  - A reinvestigation of the absolute rate constants of the metathesis reactions
      C2H5* + HBr -> C2H6 + Br* (R1) and C2H5* + HI -> C2H6 + I* (R2) has been
      performed and led to the following Arrhenius expressions: k1 = 3.69(+/-0.95) * 10
      11 exp(-10.62(+/-0.66)/RT), k2 = 1.20(+/-0.38) * 10-11 exp(-7.12(+/-1.059)/RT) in
      the temperature range 293-623 K (A/cm3 molecule-1 s-1, Ea/kJ mol-1). The study
      has been performed using a Knudsen reactor coupled to single-photon (VUV)
      photoionization mass spectrometer (SPIMS). Hydrocarbon free radicals have been
      generated externally before admission into the Knudsen reactor according to two
      different chemical schemes, enabling the generation of thermalized C2H5* free
      radicals. A minor correction to k1 and k2 for the wall loss of C2H5* (kw) has
      been applied throughout the temperature range. The obtained results are
      consistent regarding both the disappearance of C2H5* and the formation of closed
      shell products (n-C4H10, C2H4, C2H6), indicating that the chemical mechanism is
      largely understood and complete. Thermochemical parameters for C2H5* free radical
      resulting from the present kinetic measurements are discussed and point toward a
      slightly lower value for the standard heat of formation DeltafH298 degrees
      (C2H5*) compared to some presently recommended values. On the basis of the
      present results and suitable data on the reverse reaction taken from the
      literature, we recommend DeltafH298 degrees (C2H5*) = 117.3 +/- 3.1 kJ/mol
      resulting from an average of "third law" evaluations using S298 degrees (C2H5*) =
      242.9 +/- 4.6 J/K mol. The present work yields a standard heat of formation in
      satisfactory agreement with the results obtained by W. Tsang (DeltafH298 degrees
      (C2H5*) = 119 +/- 2 kJ/mol) despite using two very different experimental
      techniques.

PMID- 24134056
TI  - Development of a rapid LC-DAD/FLD method for the simultaneous determination of
      auxins and abscisic acid in plant extracts.
AB  - Plant hormones play a crucial role in controlling plant growth and development.
      These groups of naturally occurring substances trigger physiological processes at
      very low concentrations, which mandate sensitive techniques for their
      quantitation. This paper describes a method to quantify endogenous (+/-)-2-cis-4
      trans-abscisic acid, indole-3-acetic acid, indole-3-propionic acid, and indole-3
      butyric acid. The method combines high-performance liquid chromatography (HPLC)
      with diode array and fluorescence detection in a single run. Hybrid tea rose
      'Monferrato' matrices (leaves, petals, roots, seeds, androecium, gynoecium, and
      pollen) were used as references. Rose samples were separated and suspended in
      extracting methanol, after which (+/-)-2-cis-4-trans-abscisic acid and auxins
      were extracted by solvent extraction. Sample solutions were added first to cation
      solid phase extraction (SPE) cartridges and the eluates to anion SPE cartridges.
      The acidic hormones were bound to the last column and eluted with 5% phosphoric
      acid in methanol. Experimental results showed that this approach can be
      successfully applied to real samples and that sample preparation and total time
      for routine analysis can be greatly reduced. 

PMID- 24134057
TI  - Smoke-free or not: a pilot evaluation in selected Beijing Hospitals.
AB  - BACKGROUND: China enacted a policy to ban smoking in hospitals. The Chinese
      Association for Tobacco Control (CATC) developed a program to help hospitals
      implement this policy. They conducted a program and an assessment in 3 Chinese
      cities (Beijing, Shanghai and Guangdong). A more in-depth evaluation was
      implemented with a sub-sample of hospitals in Beijing (N = 7) to provide an
      independent assessment. This independent assessment focused on evaluating policy
      development and an assessment of secondhand smoke (SHS) to determine compliance
      with the smoke-free policy initiative. METHODS: Pre- and post-survey data were
      collected at each of the selected hospitals with a total sample of 2835
      physicians at pre-intervention and 2812 at post-intervention. Smoking rates pre-
      and post-policy implementation, change in knowledge, attitudes and practices
      among physicians, and compliance with policy were assessed. Measurements of
      airborne nicotine concentrations in selected locations in each hospital were
      taken: main hospital lobby; main outpatient center; emergency waiting room; and
      stairwell adjacent to a large inpatient ward. Hospital policies were collected,
      translated and rated for incorporated components necessary to implement a smoke
      free policy. RESULTS: Physicians' smoking rates decreased and attitudes towards
      tobacco control improved significantly from pre-to post-intervention. Smoking was
      still reported in certain areas of the hospital with 96% of passive nicotine
      monitors as well as self-report indicating continued smoking. Nicotine levels
      ranged from <0.0056 to 3.94 MUg/m3), with an overall mean of .667 MUg/m3.
      Hospitals that established stronger policies seemed to have lower levels of
      nicotine, suggesting a relationship between policy development and compliance.
      This finding is interesting but just suggestive and requires further
      investigation to truly demonstrate if stronger policies improve compliance and
      produce better outcomes. CONCLUSION: As implementation strategies for smoke-free
      environments are improved and more resources are focused on hospitals, China is
      making progress toward achieving smoke-free hospitals. Using a model program
      could increase the prevalence of SHS policies across China. However, relying only
      on survey data may not provide an accurate assessment of this progress, and more
      extensive evaluation efforts are useful to understand how change can and does
      occur.

PMID- 24134058
TI  - Beta-blockers in portal hypertension: new developments and controversies.
AB  - There are many studies investigating the role of non-selective beta-blockers in
      portal hypertension. Satisfactory reduction in portal pressure is possible in a
      third to half of patients with propranolol and nadolol, although combining these
      drugs with nitrates may be more effective. Carvedilol is a more potent agent than
      propranolol in reducing portal pressure, particularly in non-responders, and is
      better tolerated. All these drugs have been studied in primary and secondary
      prophylaxis, sometimes in combination with band ligation and/or nitrates. There
      is some evidence to support combining these agents with band ligation, despite a
      lack of survival benefit and increased adverse events. Hemodynamic monitoring can
      help select non-responders who may benefit from additional therapies such as band
      ligation, as lack of response is associated with worse outcomes. Propranolol
      should be used with caution in patients with refractory ascites, although the
      current evidence is not of sufficient quality to justify not using these drugs in
      such situations. Beta-blockers have been shown to reduce bacterial translocation
      and spontaneous bacterial peritonitis in cirrhosis. 

PMID- 24134059
TI  - Magnetic resonance elastography of the liver in patients status-post fontan
      procedure: feasibility and preliminary results.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of
      performing magnetic resonance elastography (MRE) as a screening tool for elevated
      liver stiffness in patients' status-post Fontan procedure. BACKGROUND: With
      greater numbers of Fontan patients surviving far into adulthood, a factor
      increasingly affecting long-term prognosis is the presence of hepatic congestion
      and fibrosis. If detected early, steps can be taken to potentially slow or halt
      the progression of fibrosis. MRE is a relatively new, noninvasive imaging
      technique, which can quantitatively measure liver stiffness and provide an
      estimate of the extent of fibrosis. METHODS: A retrospective study was conducted
      using MRE to evaluate liver stiffness in patients with a history of Fontan
      procedure. An MRE was performed in the same session as a clinical cardiac MRI.
      The liver was interrogated at four slice locations, and a mean liver stiffness
      value was calculated for each patient using postprocessing software. The medical
      records were reviewed for demographic and clinical characteristics. RESULTS:
      During the time frame of this investigation, 17 MRE exams were performed on 16
      patients. All patients had elevated liver stiffness values as defined by MRE
      standards. The median of the individual mean liver stiffness values was 5.1 kPa
      (range: 3.4-8.2 kPa). This range of liver stiffness elevation would suggest the
      presence of mild to severe fibrosis in a patient with standard cardiovascular
      anatomy. We found a significant trend toward higher liver stiffness values with
      greater duration of Fontan circulation (rs = 0.55, P = .02). CONCLUSION: Our
      preliminary findings suggest that MRE is a feasible method for evaluating the
      liver in Fontan patients who are undergoing surveillance cardiac MRI. Further
      investigation with histologic correlation is needed to determine the
      contributions of hepatic congestion and fibrosis to the liver stiffness in this
      population.

PMID- 24134060
TI  - Simultaneous irrigation and negative pressure wound therapy enhances wound
      healing and reduces wound bioburden in a porcine model.
AB  - Infected foot wounds are one of the most common reasons for hospitalization and
      amputation among persons with diabetes. The objective of the study was to
      investigate a new wound therapy system that employs negative pressure wound
      therapy (NPWT) with simultaneous irrigation therapy. For this study, we used a
      porcine model with full-thickness excisional wounds, inoculated with Pseudomonas
      aeruginosa. Wounds were treated for 21 days of therapy with either NPWT, NPWT
      with simultaneous irrigation therapy using normal saline or polyhexanide
      biguanide (PHMB) at low or high flow rates, or control. Data show that NPWT with
      either irrigation condition improved wound healing rates over control-treated
      wounds, yet did not differ from NPWT alone. NPWT improved bioburden over control
      treated wounds. NPWT with simultaneous irrigation further reduced bioburden over
      control and NPWT-treated wounds; however, flow rate did not affect these
      outcomes. Together, these data show that NPWT with simultaneous irrigation
      therapy with either normal saline or PHMB has a positive effect on bioburden in a
      porcine model, which may translate clinically to improved wound healing outcomes.

PMID- 24134061
TI  - Early consolidation of development and physiology of an identified presynaptic
      nerve terminal.
AB  - BACKGROUND: A central objective in the field of neurobiology is to understand the
      developmental plasticity of neurons. The pursuit of this objective has revealed
      the presence of critical periods in neural development. Here, critical periods
      are defined as developmental time windows during which neural remodeling can take
      place; outside of these times neural plasticity is reduced. We have taken
      advantage of transgenic technology at the Drosophila melanogaster neuromuscular
      junction (NMJ) to investigate developmental plasticity and critical period
      determination of an identifiable nerve terminal. RESULTS: Using temperature
      dependent Gal80 control of transgene expression, we regulated the expression of
      dNSF2E/Q, a dominant-negative version of the Drosophila NSF2 gene, by shifting
      developing embryos and larvae between permissive and restrictive temperatures.
      dNSF2E/Q reduces synaptic strength and causes tremendous overgrowth of the
      neuromuscular junctions. We therefore measured synaptic transmission and synaptic
      morphology in two temperature-shift paradigms. Our data show that both
      physiological and morphological development is susceptible to dNSF2E/Q
      perturbation within the first two days. CONCLUSION: Our data support the view
      that individual motor neurons in Drosophila larvae possess a critical window for
      synapse development in the first one to two days of life and that the time period
      for morphological and physiological plasticity are not identical. These studies
      open the door to further molecular genetic analysis of critical periods of
      synaptic development.

PMID- 24134062
TI  - Diffusion-controlled reference material for VOC emissions testing: effect of
      temperature and humidity.
AB  - A polymethylpentene film loaded with toluene is being developed as a reference
      material to support the reliable measurement of volatile organic compound
      emissions from building materials using environmental chambers. Earlier studies
      included the measurement of the material-phase diffusion coefficient (D) and
      material/air partition coefficient (K) at 23 degrees C. A fundamental mass
      transfer model can then be used to predict toluene emissions from the reference
      material at 23 degrees C, serving as a reference for validating chamber-measured
      emission profiles. In this study, the effect of temperature and humidity on
      performance of the reference material was investigated. Reference material
      emissions were measured at 10, 23, and 30 degrees C and at different relative
      humidity (RH) levels. D and K at different temperatures and RH were determined
      using an independent method. Results showed that RH does not significantly affect
      D and K and had no effect on emissions. However, emissions increased
      substantially at elevated temperatures due to the relationship between D and
      temperature. A statistical analysis shows good agreement between model-predicted
      and measured gas-phase concentrations, indicating that the model can accurately
      predict emission profiles as a function of temperature. The reference material
      can therefore be applied to a wide range of emission chamber testing conditions.
      PRACTICAL IMPLICATIONS: A reference material with a dynamic emissions profile was
      previously developed as a validation tool for emission testing in chambers. This
      follow-up study investigated the effect of temperature and humidity on the
      performance of the reference material. The results show that the reference
      material can be used to calibrate and validate chamber testing procedures over a
      broad range of environmental conditions.

PMID- 24134063
TI  - Using modular psychotherapy in school mental health: provider perspectives on
      intervention-setting fit.
AB  - The "fit" or appropriateness of well-researched interventions within usual care
      contexts is among the most commonly cited, but infrequently researched, factors
      in the successful implementation of new practices. The current study was
      initiated to address two exploratory research questions: How do clinicians
      describe their current school mental health service delivery context? and How do
      clinicians describe the fit between modular psychotherapy and multiple levels of
      the school mental health service delivery context? Following a year-long training
      and consultation program in an evidence-based, modular approach to psychotherapy,
      semistructured qualitative interviews were conducted with 17 school-based mental
      health providers to evaluate their perspectives on the appropriateness of
      implementing the approach within a system of school-based health centers.
      Interviews were transcribed and coded for themes using conventional and directed
      content analysis. Findings identified key elements of the school mental health
      context including characteristics of the clinicians, their practices, the school
      context, and the service recipients. Specific evaluation of intervention-setting
      appropriateness elicited many comments about both practical and value-based
      (e.g., cultural considerations) aspects at the clinician and client levels but
      fewer comments at the school or organizational levels. Results suggest that a
      modular approach may fit well with the school mental health service context,
      especially along practical aspects of appropriateness. Future research focused on
      the development of methods for routinely assessing appropriateness at different
      stages of the implementation process is recommended. 

PMID- 24134064
TI  - National consultation informing development of guidelines for a palliative
      approach for aged care in the community setting.
AB  - AIM: This study aimed to obtain perspectives from key stakeholders to inform the
      development of Australian national guidelines for a palliative approach to aged
      care in the community setting. METHODS: A descriptive, exploratory qualitative
      design was used. Sampling was purposive. Data were collected during audiotaped,
      semistructured, individual and focus group interviews that addressed the need for
      the guidelines and aimed to identify practice areas for inclusion. Thematic
      analysis was undertaken. RESULTS: Interviews were conducted across Australia and
      included 172 participants: health-care providers, consumers, volunteers and
      researchers/educators. Themes emerging from the data were: Provision of a
      Palliative Approach in Community Aged Care, Carer Support, Advance Care Planning,
      Physical and Psychological Symptom Assessment and Management, Psychosocial
      Support, Spiritual Support, Issues for Aboriginal or Torres Strait Islander
      People, Older People from Diverse Cultural and Language Groups, and Clients with
      Special Needs. CONCLUSION: Findings underpinned development of new guideline
      documents.

PMID- 24134065
TI  - Suprasegmental lexical stress cues in visual speech can guide spoken-word
      recognition.
AB  - Visual cues to the individual segments of speech and to sentence prosody guide
      speech recognition. The present study tested whether visual suprasegmental cues
      to the stress patterns of words can also constrain recognition. Dutch listeners
      use acoustic suprasegmental cues to lexical stress (changes in duration,
      amplitude, and pitch) in spoken-word recognition. We asked here whether they can
      also use visual suprasegmental cues. In two categorization experiments, Dutch
      participants saw a speaker say fragments of word pairs that were segmentally
      identical but differed in their stress realization (e.g., 'ca-vi from cavia
      "guinea pig" vs. 'ka-vi from kaviaar "caviar"). Participants were able to
      distinguish between these pairs from seeing a speaker alone. Only the presence of
      primary stress in the fragment, not its absence, was informative. Participants
      were able to distinguish visually primary from secondary stress on first
      syllables, but only when the fragment-bearing target word carried phrase-level
      emphasis. Furthermore, participants distinguished fragments with primary stress
      on their second syllable from those with secondary stress on their first syllable
      (e.g., pro-'jec from projector "projector" vs. 'pro-jec from projectiel
      "projectile"), independently of phrase-level emphasis. Seeing a speaker thus
      contributes to spoken-word recognition by providing suprasegmental information
      about the presence of primary lexical stress.

PMID- 24134066
TI  - Rauhut-Currier-type reaction with Morita-Baylis-Hillman carbonates of 2
      cyclohexenone and alkylidenemalononitriles to access chromene derivatives.
AB  - An assembly of MBH carbonates of cyclohexen-2-one and alkylidenemalononitriles
      was investigated by the catalysis of a tertiary amine, which efficiently provides
      aromatic chromene derivatives with dense functionalities through a domino Rauhut
      Currier-type reaction, cyclization, and isomerization process under metal-free
      conditions. 

PMID- 24134067
TI  - Localized cutaneous immunoglobulin G4.

PMID- 24134069
TI  - A technique for laparoscopic peritoneal entry after abdominoplasty.
AB  - BACKGROUND AND OBJECTIVES: The fascial anatomy of the anterior midline of the
      abdominal wall is permanently altered by the vertical plication of the rectus
      abdominis muscles commonly performed during abdominoplasty. In order to achieve
      safe and expeditious peritoneal entry in patients undergoing laparoscopy after a
      previous abdominoplasty, a modification of the standard midline open technique
      was developed. This not only facilitates entry and insufflation, but it also
      provides an acceptable cosmetic result following the laparoscopic surgery.
      MATERIALS AND METHODS: A modified midline open Hasson technique of laparoscopic
      peritoneal entry that addresses the anatomical distortion created by a previous
      midline fascial plication was used in 24 consecutive patients undergoing elective
      laparoscopic cholecystectomy and is described herein. RESULTS AND CONCLUSIONS:
      This modified entry technique consistently allowed safe and expeditious
      peritoneal entry in 24 consecutive patients undergoing laparoscopic surgery after
      a previous abdominoplasty.

PMID- 24134070
TI  - A novel method for creating working space during endoscopic thyroidectomy via
      bilateral areolar approach.
AB  - BACKGROUND: Endoscopic thyroidectomy (ET) can be performed through the bilateral
      areolar approach (BAA). A working space (WS) is typically created on the surface
      of the pectoral fascia in the chest wall and in the subplatysmal space in the
      neck. There are several limitations of using this WS. The aim of this study was
      to establish a new WS for ET. SUBJECTS AND METHODS: A retrospective review was
      performed on 85 patients with benign thyroid nodules who had undergone ET through
      a BAA. A WS was created between the anterior and poster layers of the superficial
      pectoral fascia (SPF) in the chest and underneath the deep layer of the investing
      layer (IL) in the neck. RESULTS: The time for creating the WS was 7.2 +/- 2.1
      (range, 5-12) minutes. No hemorrhage occurred during the procedure. Fat
      liquefaction occurred in 2 patients. Edema of the neck skin flap presented as
      lack of a suprasternal notch. No skin numbness occurred. No patient required
      postoperative pain medication. All patients were extremely satisfied with the
      cosmetic results. CONCLUSIONS: This new method of establishing a WS between the
      two layers of the SPF and underneath the IL is simple and fast, provides good
      exposure, yields less postoperative pain, and has a lower risk of skin burn.

PMID- 24134071
TI  - Diagnostic value of laparoscopy, abdominal computed tomography, and
      ultrasonography in acute appendicitis.
AB  - BACKGROUND: The most efficient approach to diagnosis of acute appendicitis (AA)
      continues to be a challenge. We sought to determine diagnostic accuracy,
      sensitivity, and specificity of computed tomography (CT), ultrasonography, and
      laparoscopy and compared benefits and advantages in patients with suspected AA.
      PATIENTS AND METHODS: A retrospective review of all patients who had laparoscopic
      surgery between January 2000 and December 2009 was conducted. Preoperative
      information, surgery results, and outcomes were compared. RESULTS: Of 887
      laparoscopic procedures performed for suspected AA, 254 (29%) patients had
      preoperative imaging: 171 CT scans and 83 ultrasound (US) scans. Overall, 754
      patients underwent laparoscopic appendectomy (LA), and 133 underwent diagnostic
      laparoscopy (DL). DL was negative in 23 patients. The sensitivity of LA was
      higher than that of CT (98% versus 94%), whereas the specificity of LA was higher
      than that of CT and US in complicated appendicitis and in women. Complicated AA
      was significantly less common in patients who underwent laparoscopic surgery
      compared with patients evaluated by preoperative CT. Comparing the kappa value
      between the preoperative diagnosis by imaging and DL, a weak agreement was found
      (kappa=0.234 +/- 0.057). CONCLUSIONS: Laparoscopy achieves early and accurate
      diagnosis of AA and can reduce the incidence of perforated appendicitis.
      Abdominal CT remains a valuable diagnostic tool. DL is useful in the early stages
      of the diagnostic work-up and avoids unnecessary exposure to radiation of the
      abdomen and pelvis in young women.

PMID- 24134068
TI  - Population pharmacokinetic-pharmacodynamic modelling in oncology: a tool for
      predicting clinical response.
AB  - In oncology trials, overall survival (OS) is considered the most reliable and
      preferred endpoint to evaluate the benefit of drug treatment. Other relevant
      variables are also collected from patients for a given drug and its indication,
      and it is important to characterize the dynamic effects and links between these
      variables in order to improve the speed and efficiency of clinical oncology drug
      development. However, the drug-induced effects and causal relationships are often
      difficult to interpret because of temporal differences. To address this,
      population pharmacokinetic-pharmacodynamic (PKPD) modelling and parametric time
      to-event (TTE) models are becoming more frequently applied. Population PKPD and
      TTE models allow for exploration towards describing the data, understanding the
      disease and drug action over time, investigating relevance of biomarkers,
      quantifying patient variability and in designing successful trials. In addition,
      development of models characterizing both desired and adverse effects in a
      modelling framework support exploration of risk-benefit of different dosing
      schedules. In this review, we have summarized population PKPD modelling analyses
      describing tumour, tumour marker and biomarker responses, as well as adverse
      effects, from anticancer drug treatment data. Various model-based metrics used to
      drive PD response and predict OS for oncology drugs and their indications are
      also discussed. 

PMID- 24134072
TI  - Psychophysiological responses to visceral and somatic pain in functional chest
      pain identify clinically relevant pain clusters.
AB  - BACKGROUND: Despite chronic pain being a feature of functional chest pain (FCP)
      its experience is variable. The factors responsible for this variability remain
      unresolved. We aimed to address these knowledge gaps, hypothesizing that the
      psychophysiological profiles of FCP patients will be distinct from healthy
      subjects. METHODS: 20 Rome III defined FCP patients (nine males, mean age 38.7
      years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched
      controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and
      personality traits measured. Subjects had sympathetic and parasympathetic nervous
      system parameters measured at baseline and continuously thereafter. Subjects
      received standardized somatic (nail bed pressure) and visceral (esophageal
      balloon distension) stimuli to pain tolerance. Venous blood was sampled for
      cortisol at baseline, post somatic pain and post visceral pain. KEY RESULTS:
      Patients had higher neuroticism, state and trait anxiety, and depression scores
      but lower extroversion scores vs controls (all p < 0.005). Patients tolerated
      less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher
      cortisol at baseline, and following pain (all p < 0.001). At baseline, patients
      had a higher sympathetic tone (p = 0.04), whereas in response to pain they
      increased their parasympathetic tone (p <= 0.008). The amalgamating the data, we
      identified two psychophysiologically distinct 'pain clusters'. Patients were
      overrepresented in the cluster characterized by high neuroticism, trait anxiety,
      baseline cortisol, pain hypersensitivity, and parasympathetic response to pain
      (all p < 0.03). CONCLUSIONS & INFERENCES: In future, such delineations in FCP
      populations may facilitate individualization of treatment based on
      psychophysiological profiling.

PMID- 24134073
TI  - Morphological alterations in the tympanic membrane affected by tympanosclerosis:
      ultrastructural study.
AB  - The ultrastructure of tympanoslerotic tissue, surgically excised from patients,
      has been studied with particular reference to the morphological changes of the
      connective tissue components and mineralization. Detailed analysis revealed the
      combination of degenerative and fibroplastic alterations, especially in the
      circular fibrous layer of the thickened lamina propria. In the biological
      material in this study the authors recognized different stages of calcium plaque
      development with discrete, moderate, and severe degree of mineralization.
      Extracellular matrix vesicles, with or without calcareous deposits, released by
      degenerating fibroblasts were prominent. In these biopsies no distinct
      morphological features of an inflammatory reaction were seen.

PMID- 24134074
TI  - Oral dextrose for analgesia in neonates during nasogastric tube insertion: a
      randomised controlled trial.
AB  - AIM: This study aims to determine if oral dextrose solution can mitigate the pain
      response to nasogastric tube (NGT) insertion in neonates. METHODS: The study was
      a double-blinded, placebo-controlled, randomised controlled trial. One hundred
      and fifty consecutive neonates were randomised into three groups to receive 25%
      dextrose (D25), or 10% dextrose (D10) or placebo (distilled water). An NGT was
      inserted after giving 2 mL of one of the solutions orally. Pain response was
      assessed using the Premature Infant Pain Profile (PIPP), and the duration of cry
      was noted within 60 s of the intervention. Total PIPP score, duration of cry,
      change in heart rate and oxygen saturation (SpO2 ) were compared among the three
      groups. RESULTS: Neonates who received D25 had significantly lesser pain response
      to NGT insertion in terms of lower PIPP score (P < 0.05) and duration of cry (P =
      0.001) compared to D10. There was a significantly smaller increase in heart rate
      and decrease in SpO2 (P < 0.05). In comparison with placebo, D10 significantly
      decreased duration of cry (P < 0.05) but not PIPP score. CONCLUSION: Oral D25 was
      effective in reducing the pain response during NGT insertion in neonates when
      compared with oral D10 and placebo. Oral D10 was not found to have a potent
      analgesic effect for the same.

PMID- 24134075
TI  - False identification use among college students increases the risk for alcohol
      use disorder: results of a longitudinal study.
AB  - BACKGROUND: It is well known that using false identification (ID) is a common
      method by which underage youth in the United States obtain alcohol. While false
      ID use is associated with high-risk drinking patterns, its association with
      alcohol use disorder (AUD), independent of other risk factors, has not been
      firmly established. METHODS: Participants were 1,015 college students recruited
      from 1 university and assessed annually during their first 4 years of college.
      Latent variable growth curve modeling was used to identify significant predictors
      of false ID use and test the hypothesis that false ID use increased the risk for
      AUD, by increasing the frequency and/or quantity of alcohol use. Several other
      hypothesized risk factors for AUD were accounted for, including demographics
      (sex, race, living situation, religiosity, socioeconomic status), individual
      characteristics (childhood conduct problems, sensation-seeking, age at first
      drink), high school behaviors (high school drinking frequency, drug use), family
      factors (parental monitoring, parental alcohol problems), perception of peer
      drinking norms, and other factors related to false ID use. RESULTS: False IDs
      were used by almost two-thirds (66.1%) of the sample. False ID use frequency was
      positively associated with baseline quantity and frequency of alcohol use,
      independent of all other factors tested. False ID use was not directly related to
      AUD risk, but indirectly predicted increases in AUD risk over time through its
      association with greater increases in alcohol use frequency over time. Several
      predictors of false ID use frequency were also identified. CONCLUSIONS: False ID
      use may contribute to AUD risk by facilitating more frequent drinking. If
      replicated, these findings highlight the potential public health significance of
      policies that enforce sanctions against false ID use. Students who use false IDs
      represent an important target population for alcohol prevention activities.

PMID- 24134076
TI  - Benign metastasizing leiomyoma of the lung.
AB  - Benign leiomyomas of the uterus are uncommonly found in association with benign
      smooth muscle tumors beyond the confines of the uterus. Benign metastasizing
      leiomyoma (BML) is a rare disease in which the lung is described to be the most
      afflicted extrauterine organ. We present a brief review of the literature, along
      with case reports for four patients who were followed up after resection of a
      pulmonary lesion or after pathological confirmation by biopsy. The clinical
      course of BML varies from chronic asymptomatic appearance to rapid progression,
      leading to respiratory failure and death. Our BML patients did not complain of
      pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology
      revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high
      power field. Immunohistochemical staining was positive for actin and desmin. A
      standard treatment for BML has not yet been established. Because of the hormone
      sensitive characteristics of BML, treatments are based on hormonal manipulation
      along with either surgical or medical oophorectomy. Benign metastasizing
      leiomyoma can be observed in postmenopausal women. We observed four patients who
      did not receive adjuvant hormonal therapy because they were postmenopausal or
      perimenopausal. All patients are still healthy and show no evidence of recurrence
      or progression of the disease.

PMID- 24134078
TI  - Physicians should consider indications before ordering preoperative cardiac
      testing.

PMID- 24134077
TI  - Reasons for eating 'unhealthy' snacks in overweight and obese males and females.
AB  - BACKGROUND: Snack foods are often high in fat and sugar. Thus, reducing snack
      consumption may be a useful weight management strategy. However, individuals may
      snack for a variety of reasons with different implications for intervention. The
      present study examined the perceived reasons for eating main meals, 'unhealthy'
      snacks (i.e. snacks high in fat or sugar) and 'healthy' snacks in overweight and
      obese participants. METHODS: Over a period of 5 days, 28 males and 27 females
      completed a food diary every time they ate. As well as providing details about
      the type of eating episode and food eaten, they also rated their agreement with
      13 different reasons for eating (identified from relevant literature and a pilot
      study). RESULTS: Across a total of 1084 eating episodes, 358 were coded as
      snacks, 79% of which were high in either fat or sugar. The results showed that
      hunger and temptation (external eating) were reported as a reason for eating
      unhealthy snacks in 49% and 55% of all episodes, respectively. Eating because the
      individual was feeling fed up, bored or stressed (emotional eating) was given as
      a reason in 26% of episodes. CONCLUSIONS: These findings point to the potential
      utility of intervention strategies that target cravings, enhance self-control or
      promote stimulus control.

PMID- 24134081
TI  - General health checks for reducing morbidity and mortality.

PMID- 24134082
TI  - Ultrasound-guided steroid injections for shoulder pain.

PMID- 24134083
TI  - Otitis media: diagnosis and treatment.
AB  - Acute otitis media is diagnosed in patients with acute onset, presence of middle
      ear effusion, physical evidence of middle ear inflammation, and symptoms such as
      pain, irritability, or fever. Acute otitis media is usually a complication of
      eustachian tube dysfunction that occurs during a viral upper respiratory tract
      infection. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis are the most common organisms isolated from middle ear fluid.
      Management of acute otitis media should begin with adequate analgesia. Antibiotic
      therapy can be deferred in children two years or older with mild symptoms. High
      dose amoxicillin (80 to 90 mg per kg per day) is the antibiotic of choice for
      treating acute otitis media in patients who are not allergic to penicillin.
      Children with persistent symptoms despite 48 to 72 hours of antibiotic therapy
      should be reexamined, and a second-line agent, such as amoxicillin/clavulanate,
      should be used if appropriate. Otitis media with effusion is defined as middle
      ear effusion in the absence of acute symptoms. Antibiotics, decongestants, or
      nasal steroids do not hasten the clearance of middle ear fluid and are not
      recommended. Children with evidence of anatomic damage, hearing loss, or language
      delay should be referred to an otolaryngologist. 

PMID- 24134084
TI  - Dermoscopy for the family physician.
AB  - Noninvasive in vivo imaging techniques have become an important diagnostic aid
      for skin cancer detection. Dermoscopy, also known as dermatoscopy,
      epiluminescence microscopy, incident light microscopy, or skin surface
      microscopy, has been shown to increase the clinician's diagnostic accuracy when
      evaluating cutaneous neoplasms. A handheld instrument called a dermatoscope or
      dermoscope, which has a transilluminating light source and standard magnifying
      optics, is used to perform dermoscopy. The dermatoscope facilitates the
      visualization of subsurface skin structures that are not visible to the unaided
      eye. The main purpose for using dermoscopy is to help correctly identify lesions
      that have a high likelihood of being malignant (i.e., melanoma or basal cell
      carcinoma) and to assist in differentiating them from benign lesions clinically
      mimicking these cancers. Colors and structures visible with dermoscopy are
      required for generating a correct diagnosis. Routinely using dermoscopy and
      recognizing the presence of atypical pigment network, blue-white color, and
      dermoscopic asymmetry will likely improve the observer's sensitivity for
      detecting pigmented basal cell carcinoma and melanoma. A two-step algorithm based
      on a seven-level criterion ladder is the foundation for dermoscopic evaluation of
      skin lesions. The first step of the algorithm is intended to help physicians
      differentiate melanocytic lesions from the following nonmelanocytic lesions:
      dermatofibroma, basal cell carcinoma, seborrheic keratosis, and hemangioma. The
      second step is intended to help physicians differentiate nevi from melanoma using
      one of several scoring systems. From a management perspective, the two-step
      algorithm is intended to guide the decision-making process on whether to perform
      a biopsy, or to refer or reassure the patient. 

PMID- 24134085
TI  - Recognition and evaluation of nontraumatic subarachnoid hemorrhage and ruptured
      cerebral aneurysm.
AB  - Swift diagnosis and treatment are critical for good outcomes in patients with
      nontraumatic subarachnoid hemorrhage, which is usually caused by a ruptured
      aneurysm. This type of stroke often results in death or disability. Rates of
      misdiagnosis and treatment delays for subarachnoid hemorrhage have improved over
      the years, but these are still common occurrences. Subarachnoid hemorrhage can be
      more easily diagnosed in patients who present with severe symptoms,
      unconsciousness, or with thunderclap headache, which is often accompanied by
      vomiting. The diagnosis is more elusive in patients who present in good
      condition, yet these patients have the best chance for good outcome if they are
      correctly diagnosed at the time of presentation. Physicians should be alert for
      warning headaches, which are often severe, and headaches that feel different to
      the patient. Other symptoms may include nausea, vomiting, impaired consciousness,
      nuchal rigidity, orbital pain, focal neurologic deficits, dysphasia,
      lightheadedness, and dizziness. The most important risk factors for subarachnoid
      hemorrhage include cigarette smoking, hypertension, heavy alcohol use, and
      personal or family history of aneurysm or hemorrhagic stroke. The first step in
      the diagnostic workup is noncontrast computed tomography of the head. If computed
      tomography is negative or equivocal, a lumbar puncture should be performed.
      Subsequent imaging may include computed tomographic angiography, catheter
      angiography, and magnetic resonance angiography. 

PMID- 24134086
TI  - Photosensitive erythematous skin rash.

PMID- 24134088
TI  - Do abstracts of articles in major journals contain the same information as the
      body of the paper?

PMID- 24134091
TI  - Should children with acute otitis media routinely be treated with antibiotics?
      No: most children older than two years do not require antibiotics.

PMID- 24134092
TI  - Should children with acute otitis media routinely be treated with antibiotics?
      Yes: routine treatment makes sense for symptomatic, emotional, and economic
      reasons.

PMID- 24134093
TI  - Historic growth rates vary widely across the primary care physician disciplines.

PMID- 24134094
TI  - Minnesota smokers' perceived helpfulness of 2009 federal tobacco tax increase in
      assisting smoking cessation: a prospective cohort study.
AB  - BACKGROUND: The cost of cigarettes has been cited as a motivating factor for
      smokers to quit smoking, and a cigarette tax increase is an effective way to
      increase the cost of cigarettes. Scholars have suggested that smokers may see
      cigarette tax increases as commitment devices to help them quit smoking. Little
      is known about whether smokers actually think cigarette tax increases help them
      quit, and whether this perception predicts subsequent smoking cessation
      behaviors. We used data from the Minnesota Adult Tobacco Survey Cohort Study
      collected after the 2009 federal tobacco tax increase to answer these questions.
      METHODS: In 2009, 727 smokers were asked whether they thought the federal tobacco
      tax increase helped them to: (1) think about quitting, (2) cut down on
      cigarettes, and (3) make a quit attempt. We also collected data on demographics,
      number of cigarette price-minimizing strategies used, and cigarette consumption.
      In 2010, we assessed if these smokers had made a quit attempt, had cut down on
      their cigarette consumption, and had stopped smoking. Logistic regression models
      were used to assess the characteristics associated with the perceptions that the
      tax increase was helpful in assisting smoking cessation, and the association
      between these perceptions in 2009 and cessation behaviors in 2010. RESULTS:
      Overall, 65% of the sample thought that the 2009 tax increase helped them think
      about quitting, 47% thought it helped them cut down on cigarettes, and 29%
      thought it helped them make a quit attempt. Lower education, lower income, lower
      cigarette consumption, and using more cigarette price-minimizing strategies were
      associated with the perceptions that the tax increase was helpful in assisting
      smoking cessation (p < 0.05). Smokers who perceived the tax increase as helpful
      in assisting smoking cessation were more likely than those who did not perceive
      the tax increase as helpful to report making a quit attempt in 2010 (p < 0.05).
      CONCLUSIONS: A significant proportion of smokers in our sample thought the 2009
      federal tobacco tax increase was helpful in assisting smoking cessation,
      particularly among smokers of lower socio-economic status. Health communication
      interventions to promote cigarette tax increases as an opportunity for smoking
      cessation may further assist quit attempts.

PMID- 24134096
TI  - There is no free lunch--really.

PMID- 24134095
TI  - 670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina.
AB  - BACKGROUND: Irradiation with light wavelengths from the far red (FR) to the near
      infrared (NIR) spectrum (600 nm -1000 nm) has been shown to have beneficial
      effects in several disease models. In this study, we aim to examine whether 670
      nm red light pretreatment can provide protection against hyperoxia-induced damage
      in the C57BL/6J mouse retina. Adult mice (90-110 days) were pretreated with 9
      J/cm2 of 670 nm light once daily for 5 consecutive days prior to being placed in
      hyperoxic environment (75% oxygen). Control groups were exposed to hyperoxia, but
      received no 670 nm light pretreatment. Retinas were collected after 0, 3, 7, 10
      or 14 days of hyperoxia exposure (n = 12/group) and prepared either for
      histological analysis, or RNA extraction and quantitative polymerase chain
      reaction (qPCR). Photoreceptor damage and loss were quantified by counting
      photoreceptors undergoing cell death and measuring photoreceptor layer thickness.
      Localization of acrolein, and cytochrome c oxidase subunit Va (Cox Va) were
      identified through immunohistochemistry. Expression of heme oxygenase-1 (Hmox-1),
      complement component 3 (C3) and fibroblast growth factor 2 (Fgf-2) genes were
      quantified using qPCR. RESULTS: The hyperoxia-induced photoreceptor loss was
      accompanied by reduction of metabolic marker, Cox Va, and increased expression of
      oxidative stress indicator, acrolein and Hmox-1. Pretreatment with 670 nm red
      light reduced expression of markers of oxidative stress and C3, and slowed, but
      did not prevent, photoreceptor loss over the time course of hyperoxia exposure.
      CONCLUSION: The damaging effects of hyperoxia on photoreceptors were ameliorated
      following pretreatment with 670 nm light in hyperoxic mouse retinas. These
      results suggest that pretreatment with 670 nm light may provide stability to
      photoreceptors in conditions of oxidative stress.

PMID- 24134097
TI  - Medical assistants.

PMID- 24134098
TI  - Skepticism.

PMID- 24134099
TI  - Hospital employment.

PMID- 24134100
TI  - Correction.

PMID- 24134101
TI  - The Sunshine Act: how to avoid getting burned.

PMID- 24134102
TI  - Three building blocks for improving access to care.

PMID- 24134103
TI  - Practice transformation: running your business like a business.

PMID- 24134105
TI  - Working with international populations--abroad or in your own backyard.

PMID- 24134104
TI  - Practical realities of doing volunteer medical work in the developing world.

PMID- 24134114
TI  - iGeriatrics.

PMID- 24134115
TI  - Six essential relationships in health care.

PMID- 24134117
TI  - Family history of hepatocellulcar carcinoma is not associated with its patients'
      prognosis after hepatectomy.
AB  - BACKGROUND: Family history of liver cancer is a major risk factor for
      hepatocellular carcinoma (HCC). In this study, we investigated the prognosis of
      patients with HCC with or without family history. METHODS: Data for 1,313
      patients who underwent hepatectomy as initial treatment for HCC between 2000 and
      2008 at a tertiary cancer center hospital were retrieved from a prospective
      database. A positive family history was defined as a self-reported history of HCC
      in first-degree relatives. Clinicopathologic characteristics were compared by
      family history. Kaplan-Meier method and Cox proportional hazards regressions were
      applied for overall survival (OS) and disease-free survival (DFS). RESULTS: Of
      1,313 patients, 169 patients (12.9%) had first-degree relatives with a history of
      HCC. There were no significant differences between patients with or without
      family history in basic clinicopathologic characteristics. In either whole group
      or each stage according to the TNM staging system, first-degree family history
      was not associated with survival in all patients, hepatitis B virus-positive
      patients, as well as male patients. Multivariate analysis revealed that first
      degree family history was not a prognostic factor, either for OS or DFS.
      CONCLUSION: A first-degree family history of HCC is not associated with its
      patients' prognosis after hepatectomy.

PMID- 24134118
TI  - Induction of protein expression within Escherichia coli vector for entry into
      mammalian cells.
AB  - Direct protein delivery into the cytosol of mammalian cells by invasive
      Escherichia coli (E. coli) bacterial vector will bypass the need to achieve
      nuclear entry and transcription of DNA, a major hurdle that is known to seriously
      limit gene transfer. The bacterial vector is induced to express the protein
      during its growth phase, before presentation for entry into mammalian cells and
      release of its content into the cellular environment. For this class of vector,
      crossing the plasma membrane becomes the primary step that determines the success
      of protein delivery. Yet, how the mechanics of protein expression within the
      vector affect its entry into the host is poorly understood. We found the vector's
      effectiveness to enter HeLa cells diminished together with its viability when
      phage N15 protelomerase (TelN) expression was induced continuously in the
      invasive E. coli despite producing an abundant amount of functional protein. By
      comparison, shorter induction, even as little as 3 hr, produced sufficient
      amounts of functional TelN and showed more effective invasion of HeLa cells,
      comparable to that of uninduced invasive E. coli. These results demonstrate that
      brief induction of protein expression during vector growth is essential for
      optimal entry into mammalian cells, an important step for achieving bacteria
      mediated protein delivery.

PMID- 24134119
TI  - Pineal oscillator functioning in the chicken--effect of photoperiod and
      melatonin.
AB  - The avian pineal gland, apart from the hypothalamic master clock (suprachiasmatic
      nuclei, SCN) and retina, functions as an independent circadian oscillator,
      receiving external photic cues that it translates into the rhythmical synthesis
      of melatonin, a biochemical signal of darkness. Functional similarity to the
      mammalian SCN makes the avian pineal gland a convenient model for studies on
      biological clock mechanisms in general. Pineal melatonin is produced not only in
      a light-dependent manner but also remains under the control of the endogenous
      oscillator, while the possible involvement of melatonin in maintaining cyclic
      expression of the avian clock genes remains to be elucidated. The aim of the
      present study was to characterize the diurnal profiles of main clock genes
      transcription in the pineal glands of chickens exposed to continuous light (LL)
      and supplemented with exogenous melatonin. We hypothesized that rearing chickens
      from the day of hatch under LL conditions would evoke a functional pinealectomy,
      influencing, in turn, pineal clock function. To verify this hypothesis, we
      examined the diurnal transcriptional profiles of selected clock genes as well as
      the essential parameters of pineal gland function: transcription of the genes
      encoding arylalkylamine N-acetyltransferase (Aanat), a key enzyme in melatonin
      biosynthesis, and the melatonin receptor (Mel1c), along with the blood melatonin
      level. Chickens hatched in summer or winter were maintained under LD 16:8 and
      8:16, corresponding to the respective photoperiods, as the seasonal control
      groups. Another set of chickens was kept in parallel under LL conditions and some
      were supplemented with melatonin to check the ability of exogenous hormone to
      antagonize the effects evoked by continuous light. Twelve-day-old chickens were
      sacrificed every 3 h over a 24-h period and the mRNAs of selected clock genes,
      Bmal1, Cry1, Per3, E4bp4, together with those of Aanat and Mel1c, were quantified
      in the isolated pineal glands. Our results indicate that the profiles of clock
      gene transcription are not dependent on the duration of the light phase, while LL
      conditions decrease the amplitude of diurnal changes, but do not abolish them
      entirely. Melatonin supplied in drinking water to the birds kept in LL seems to
      desynchronize transcription of the majority of clock genes in the summer, while
      in the winter, it restores the pattern, but not the diurnal rhythmicity. Rhythmic
      expression of Bmal1 appears to provide a direct link between the circadian clock
      and the melatonin output pathway, while the availability of cyclic melatonin is
      clearly involved in the canonical transcription pattern of Per3 in the chicken
      pineal gland. Regardless of the experimental conditions, a negative correlation
      was identified between the transcription of genes involved in melatonin
      biosynthesis (Aanat) and melatonin signal perception (Mel1c receptor). 

PMID- 24134120
TI  - Visible-light-promoted selenofunctionalization of alkenes.
AB  - A visible-light-promoted method for the selenofunctionalization (and
      tellurofunctionalization) of alkenes has been developed. This method obviates the
      prepreparation of moisture-sensitive chalcogen electrophiles. The experimental
      setup is simple, and superior yields are obtained in the case of
      selenofunctionalization (up to 99%) while moderate to good yields are obtained in
      the case of tellurofunctionalization (53-75%). A variety of intra- and
      intermolecular processes and a short synthesis of the Amaryllidaceae alkaloid (+/
      )-gamma-lycorane are demonstrated with this method. 

PMID- 24134116
TI  - Independent associations of socioeconomic factors with disability and pain in
      adults with knee osteoarthritis.
AB  - BACKGROUND: The purpose of this study is to explore the relationship between
      function, pain and stiffness outcomes with individual and community socioeconomic
      status (SES) measures among individuals with radiographic knee osteoarthritis
      (rOA). METHODS: Cross-sectional data from the Johnston County Osteoarthritis
      Project were analyzed for adults age 45 and older with knee rOA (n = 782) and a
      subset with both radiographic and symptomatic knee OA (n = 471). Function, pain
      and stiffness were measured using the Western Ontario and McMasters Universities
      Index of Osteoarthritis (WOMAC). Individual SES measures included educational
      attainment (<12 years, >=12 years) and occupation type (managerial, non
      managerial), while community SES was measured using Census block group poverty
      rate (<12%, 12-25%, >=25%). SES measures were individually and simultaneously
      examined in linear regression models adjusting for age, gender, race, body mass
      index (BMI), occupational physical activity score (PAS), comorbidity count, and
      presence of hip symptoms. RESULTS: In analyses among all individuals with rOA,
      models which included individual SES measures were observed to show that
      occupation was significantly associated with WOMAC Function (beta =2.91, 95%
      Confidence Interval (CI) = 0.68-5.14), WOMAC Pain (beta =0.93, 95% CI = 0.26
      1.59) and WOMAC Total scores (beta =4.05, 95% CI = 1.04-7.05), and education was
      significantly associated with WOMAC Function (beta =3.57, 95% CI = 1.25-5.90) and
      WOMAC Total (beta =4.56, 95% CI = 1.41-7.70) scores. In multivariable models
      including all SES measures simultaneously, most associations were attenuated.
      However, statistically significant results for education remained between WOMAC
      Function (beta =2.83, 95% CI = 0.38-5.28) and WOMAC Total (beta =3.48, 95% CI =
      0.18-6.78), as well as for the association between occupation and WOMAC Pain
      (beta =0.78, 95% CI = 0.08-1.48). In rOA subgroup analyses restricted to those
      with symptoms, we observed a significant increase in WOMAC Pain (beta =1.36, 95%
      CI = 0.07-2.66) among individuals living in a block group with poverty rates
      greater than 25%, an association that remained when all SES measures were
      considered simultaneously (beta =1.35, 95% CI = 0.06-2.64). CONCLUSIONS: Lower
      individual and community SES are both associated with worse function and pain
      among adults with knee rOA.

PMID- 24134121
TI  - Halogen interactions in protein-ligand complexes: implications of halogen bonding
      for rational drug design.
AB  - Halogen bonding interactions between halogenated ligands and proteins were
      examined using the crystal structures deposited to date in the PDB. The data was
      analyzed as a function of halogen bonding to main chain Lewis bases, viz. oxygen
      of backbone carbonyl and backbone amide nitrogen. This analysis also examined
      halogen bonding to side-chain Lewis bases (O, N, and S) and to the electron-rich
      aromatic amino acids. All interactions were restricted to van der Waals radii
      with respective atoms. The data reveals that while fluorine and chlorine have
      strong tendencies favoring interactions with the backbone Lewis bases at glycine,
      the trend is not restricted to the achiral amino acid backbone for larger
      halogens. Halogen side-chain interactions are not restricted to amino acids
      containing O, N, and S as Lewis bases. Electron-rich aromatic amino acids host a
      high frequency of halogen bonds as does Leu. A closer examination of the latter
      hydrophobic side chain reveals that the "propensity of interactions" of halogen
      ligands at this oily residue is an outcome of strong classical halogen bonds with
      Lewis bases in the vicinity. Finally, an examination of Theta1 (C-X...O and C
      X...N) and Theta2 (X...O-Z and X...N-Z) angles reveals that very few ligands
      adopt classical halogen bonding angles, suggesting that steric and other factors
      may influence these angles. The data is discussed in the context of ligand design
      for pharmaceutical applications. 

PMID- 24134122
TI  - Synthesis and characterization of lipid immuno-nanocapsules for directed drug
      delivery: selective antitumor activity against HER2 positive breast-cancer cells.
AB  - Lipid nanocapsules (LNC) are usually developed as nanocarriers for lipophilic
      drug delivery. The surface characteristics of these colloidal particles are
      determinant for a controlled and directed delivery to target tissues with
      specific markers. We report the development of immuno-nanocapsules, in which some
      antibody molecules with different immuno-specificity are conjugated to the
      nanocapsule surface, offering the standardization of a simple method to obtain
      vectorized nanosystems with specific recognition properties. Nanocapsules were
      prepared by a solvent-displacement technique, producing an oily core coated by a
      functional shell of different biocompatible molecules and surface carboxylic
      groups. Three different antibodies (one a specific HER2 oncoprotein antibody)
      were conjugated with these nanoparticles by the carbodiimide method, which allows
      the covalent immobilization of protein molecules through carboxylic surface
      groups. The immuno-nanocapsules were completely characterized physico-chemically
      via electrokinetic and colloidal stability experiments, confirming the correct
      immobilization of these antibody molecules on the colloidal nanoparticles. Also,
      additional immunological analyses verified that these IgG-LNC complexes showed
      the expected specific immuno-response. Finally, different healthy and tumoral
      breast-cell lines were cultured in vitro with Nile-Red-loaded and docetaxel
      loaded HER2 immuno-nanocapsules. The results indicate that our immuno
      nanocapsules can increase their uptake in HER2 overexpressing tumoral cell lines.

PMID- 24134123
TI  - C-reactive protein, pre- and postdexamethasone cortisol levels in post-traumatic
      stress disorder.
AB  - BACKGROUND: Dysregulations of the hypothalamic-pituitary-adrenal axis may impact
      inflammatory processes in post-traumatic stress disorder (PTSD), possibly
      resulting in a low-grade inflammation as reflected by elevated levels of C
      reactive protein (CRP). METHODS: Serum CRP levels and salivary cortisol before
      and after the dexamethasone suppression test (DST) were assessed in 50 inpatients
      with main diagnoses PTSD, major depressive disorder or borderline personality
      disorder. RESULTS: A strong trend for lower CRP levels was found in PTSD positive
      individuals compared with patients without PTSD. CONCLUSIONS: Our study does not
      support the hypothesis of elevated serum CRP levels in PTSD compared with other
      psychiatric patients. However, a dysbalanced immune system with suppressed CRP
      might contribute to the elevated somatic comorbidity in PTSD.

PMID- 24134124
TI  - Wild-type but not mutant SOD1 transgenic astrocytes promote the efficient
      generation of motor neuron progenitors from mouse embryonic stem cells.
AB  - BACKGROUND: The efficient derivation of mature (Hb9+) motor neurons from
      embryonic stem cells is a sought-after goal in the understanding, and potential
      treatment, of motor neuron diseases. Conditions that promote the robust
      generation of motor neuron progenitors from embryonic stem cells and that promote
      the survival of differentiated motor neurons ex vivo are likely, therefore, to be
      critical in future biological/therapeutic/screening approaches. Previous studies
      have shown that astrocytes have a protective effect on differentiated motor
      neurons (in vivo and ex vivo), but it remains unclear whether astrocytes also
      play a beneficial role in the support of motor neuron progenitors. Here we
      explore the effect of murine astrocyte-conditioned medium on monolayer cultures
      of mouse embryonic stem cell-derived motor neuron progenitors. RESULTS: Our data
      show that wild-type astrocyte-conditioned medium significantly increases the
      number of Olig2+/Hb9- progenitors, which subsequently differentiate into
      Hb9+/Islet1+ post-mitotic motor neurons. Intriguingly, while astrocyte
      conditioned medium derived from mice transgenic for wild-type human SOD1 mimics
      the effect of wild-type astrocytes, conditioned medium derived from astrocytes
      carrying an amyotrophic lateral sclerosis-related SOD1-G93A mutation shows no
      such beneficial effect. The effect of astrocyte-conditioned medium, moreover, is
      specific to motor neurons: we find that interneurons generated from mouse
      embryonic stem cells are unaffected by conditioned media from any type of
      astrocyte. CONCLUSIONS: Our study indicates that conditioned medium derived from
      wild type astrocytes enhances the efficient generation of motor neurons from
      mouse embryonic stem cells by enhancing motor neuron progenitors. In contrast,
      conditioned medium from SOD1-G93A astrocytes does not show a similar enhancing
      effect.

PMID- 24134125
TI  - Evidence of semantic clustering in letter-cued word retrieval.
AB  - Letter-cued word fluency is conceptualized as a phonemically guided word
      retrieval process. Accordingly, word clusters typically are defined solely by
      their phonemic similarity. We investigated semantic clustering in two letter-cued
      (P and S) word fluency task performances by 315 healthy adults, each for 1 min.
      Singular value decomposition (SVD) and generalized topological overlap measure
      (GTOM) were applied to verbal outputs to conservatively extract clusters of high
      frequency words. The results generally confirmed phonemic clustering. However, we
      also found considerable semantic/associative clusters of words (e.g., pen,
      pencil, and paper), and some words showed both phonemic and semantic associations
      within a single cluster (e.g., pair, pear, peach). We conclude that letter-cued
      fluency is not necessarily a purely phonemic word retrieval process. Strong
      automatic semantic activation mechanisms play an important role in letter-cued
      lexical retrieval. Theoretical conceptualizations of the word retrieval process
      with phonemic cues may also need to be reexamined in light of these analyses. 

PMID- 24134126
TI  - The energy demands of portable gas analysis system carriage during walking and
      running.
AB  - The aim of this study was to evaluate the carriage of a portable gas analyser
      during prolonged treadmill exercise at a variety of speeds. Ten male participants
      completed six trials at different speeds (4, 8 and 12 km h(- 1)) for 40 min
      whilst wearing the analyser (P) or where the analyser was externally supported
      (L). Throughout each trial, respiratory gases, heart rate (HR), perceptions of
      effort and energy expenditure (EE) were measured. Significantly higher EE
      occurred during P12 (p = 0.01) than during L12 (855.3 +/- 104.3; CI = 780.7-930.0
      and 801.5 +/- 82.2 kcal; CI = 742.7-860.3 kcal, respectively), but not at the
      other speeds; despite this, perceptions of effort and HR responses were
      unaffected. This additional EE is likely caused by alterations to posture which
      increase oxygen demand. The use of such systems is unlikely to affect low
      intensity tasks, but researchers should use caution when interpreting data,
      particularly when exercise duration exceeds 30 min and laboratory-based analysers
      should be used where possible. 

PMID- 24134127
TI  - Four-way junction-driven DNA strand displacement and its application in building
      majority logic circuit.
AB  - We introduced a four-way DNA junction-driven toehold-mediated strand displacement
      method. Separation of the different functional domains on different strands in
      the four-way junction structure and usage of glue strand to recombine them for
      different logic gates make the design more flexible. On the basis of this
      mechanism, a majority logic circuit fabricated by DNA strands was designed and
      constructed by assembling three AND gates and one OR gate together. The output
      strand drew the G-rich segments together to form a split G-quadruplex, which
      could specifically bind PPIX and enhance its fluorescence. Just like a poll with
      three voters, the high fluorescence signal would be given off only when two or
      three voters vote in favor. Upon slight modification, the majority circuit was
      utilized to select the composite number from 0 to 9 represented by excess-three
      code. It is a successful attempt to integrate the logic gates into a circuit and
      to achieve desired functions. 

PMID- 24134128
TI  - Arterial ammonia levels in cirrhosis are determined by systemic and hepatic
      hemodynamics, and by organ function: a quantitative modelling study.
AB  - BACKGROUND & AIMS: Hyperammonaemia is a common complication of chronic liver
      failure. Two main factors are thought to underlie this complication: a loss of
      hepatic detoxification function and the development of portosystemic shunting.
      However, few studies have tried to quantify the importance of portosystemic
      shunting. Here, we used a theoretical approach to test the hypothesis that the
      development of portosystemic shunting is sufficient to cause hyperammonaemia in
      cirrhosis. METHODS: Two mathematical models are developed. The first one
      describes the main vascular resistances of the circulation and is used to provide
      scenarios for the distributions of organ blood flow in cirrhosis, which are
      necessary to run the second model. The second model predicts arterial ammonia
      levels resulting from ammonia metabolism in gut, liver, kidney, muscle and brain,
      and the distribution of organ blood flow. RESULTS: The fraction of
      gastrointestinal blood flow shunted through collaterals was estimated to be 41%
      in mild cirrhosis, 69% in moderate and 85% in severe cases. In the second model,
      the redistribution of organ blood flow associated with severe cirrhosis was
      sufficient to cause hyperammonaemia, even when the hepatic detoxification
      function and the ammonia production were set to normal. CONCLUSIONS: The model
      indicates that the development of portosystemic shunting in cirrhosis is
      sufficient to cause hyperammonaemia. Interventions that reduce the fraction of
      shunting may be future targets of therapy to control severity of hyperammonaemia.

PMID- 24134129
TI  - Type 2 diabetes in Asia: like chronic obstructive pulmonary disease, a threat to
      human health and wellbeing.

PMID- 24134131
TI  - Adverse effects and homeopathy: may remedies yet contain noxious or toxic
      molecules?

PMID- 24134130
TI  - The origin of projections from the posterior cingulate and retrosplenial cortices
      to the anterior, medial dorsal and laterodorsal thalamic nuclei of macaque
      monkeys.
AB  - Interactions between the posterior cingulate cortex (areas 23 and 31) and the
      retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal
      medial thalamic nuclei are thought to support various aspects of cognition,
      including memory and spatial processing. To detail these interactions better, the
      present study used retrograde tracers to reveal the origins of the
      corticothalamic projections in two closely related monkey species (Macaca
      mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only
      light cortical inputs, which predominantly arose from area 23. Efferents to the
      anterior medial thalamic nucleus also arose principally from area 23, but these
      projections proved more numerous than those to the medial dorsal nucleus and also
      involved additional inputs from areas 29 and 30. The anterior ventral and
      laterodorsal thalamic nuclei had similar sources of inputs from the posterior
      cingulate and retrosplenial cortices. For both nuclei, the densest projections
      arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when
      going dorsal from area 23a to 23c and to area 31. In all cases, the
      corticothalamic projections almost always arose from the deepest cortical layer.
      The different profiles of inputs to the anterior medial and anterior ventral
      thalamic nuclei reinforce other anatomical and electrophysiological findings
      suggesting that these adjacent thalamic nuclei serve different, but
      complementary, functions supporting memory. While the lack of retrosplenial
      connections singled out the medial dorsal nucleus, the very similar connection
      patterns shown by the anterior ventral and laterodorsal nuclei point to common
      roles in cognition.

PMID- 24134133
TI  - Abstracts of the Royal Australian and New Zealand College of Ophthalmologists
      45th Annual Scientific Congress. November 2-6, 2013. Hobart, Tasmania.

PMID- 24134137
TI  - BRCA1/2 negative status predicts no extended risk of invasive ovarian cancer.

PMID- 24134138
TI  - A single-center study of 100 consecutive patients with localized prostate cancer
      treated with stereotactic body radiotherapy.
AB  - BACKGROUND: Radiotherapy is an increasingly preferred treatment option for
      localized prostate cancer, and stereotactic body radiation therapy (SBRT) a
      relatively established modality of therapeutic irradiation. The present study
      analyzes the toxicity and biochemical efficacy of SBRT in 100 consecutive
      prostate cancer patients treated with CyberKnife Robotic Radiosurgery System.
      METHODS: One hundred patients were treated with SBRT at the Radiation Oncology
      department of San Bortolo Hospital, Vicenza, Italy. All patients included in this
      IRB-approved protocol-driven prospective study had biopsy-proven prostate cancer.
      Risk category was low in 41, intermediate in 42, and high in 17 patients. The
      patients were treated with CyberKnife-SBRT (CK-SBRT), the prescription dose was
      35 Gy in five fractions, corresponding to 92 Gy in 2-Gy fractions (alpha/beta
      =1.5 Gy); 29 patients also received androgen deprivation therapy (ADT). RESULTS:
      Median follow-up was 36 months (range, 6-76 months). Acute Grade 2 genitourinary
      and gastrointestinal toxicity occurred in respectively 12% and 18% of the
      patients; there were no Grade 3 or higher acute toxicities. Late Grade 1, 2, and
      3 genitourinary toxicities occurred in 4%, 3%, and 1% of the patients,
      respectively; late Grade 1 gastrointestinal toxicity occurred in two patients and
      Grade 2 toxicity in one patient; no late gastrointestinal toxicities of grade 3
      or 4 were observed. Median PSA nadir was 0.45 ng/ml at 36 months for all
      patients. In the SBRT-monotherapy group, the median PSA nadir at 36 months was
      0.62 ng/ml; in the ADT-SBRT group, it was 0.18 ng/ml. Four patients had clinical
      recurrence: one local, two lymph nodes, and one to the bone. Ninety-six patients
      had no evidence of biochemical or clinical recurrence. A benign PSA bounce of
      median 1.08 ng/ml occurred in 12% of the 71 SBRT monotherapy patients at a mean
      23 months (range, 18-30 months). CONCLUSIONS: In this study CK-SBRT has provided
      promising outcomes in localized prostate cancer with good PSA response, minimal
      toxicity and patient inconvenience.

PMID- 24134139
TI  - Learning difficulties or learning English difficulties? Additional language
      acquisition: an update for paediatricians.
AB  - Australia is a diverse society: 26% of the population were born overseas, a
      further 20% have at least one parent born overseas and 19% speak a language other
      than English at home. Paediatricians are frequently involved in the assessment
      and management of non-English-speaking-background children with developmental
      delay, disability or learning issues. Despite the diversity of our patient
      population, information on how children learn additional or later languages is
      remarkably absent in paediatric training. An understanding of second language
      acquisition is essential to provide appropriate advice to this patient group. It
      takes a long time (5 years or more) for any student to develop academic
      competency in a second language, even a student who has received adequate prior
      schooling in their first language. Refugee students are doubly disadvantaged as
      they frequently have limited or interrupted prior schooling, and many are unable
      to read and write in their first language. We review the evidence on second
      language acquisition during childhood, describe support for English language
      learners within the Australian education system, consider refugee-background
      students as a special risk group and address common misconceptions about how
      children learn English as an additional language. 

PMID- 24134140
TI  - SCA14 mutation V138E leads to partly unfolded PKCgamma associated with an exposed
      C-terminus, altered kinetics, phosphorylation and enhanced insolubilization.
AB  - The protein kinase C gamma (PKCgamma) undergoes multistep activation and
      participates in various cellular processes in Purkinje cells. Perturbations in
      its phosphorylation state, conformation or localization can disrupt kinase
      signalling, such as in spinocerebellar ataxia type 14 (SCA14) that is caused by
      missense mutations in PRKCG encoding for PKCgamma. We previously showed that
      SCA14 mutations enhance PKCgamma membrane translocation upon stimulation owing to
      an altered protein conformation. As the faster translocation did not result in an
      increased function, we examined how SCA14 mutations induce this altered
      conformation of PKCgamma and what the consequences of this conformational change
      are on PKCgamma life cycle. Here, we show that SCA14-related PKCgamma-V138E
      exhibits an exposed C-terminus as shown by fluorescence resonance energy transfer
      fluorescence lifetime imaging microscopy in living cells, indicative of its
      partial unfolding. This conformational change was associated with faster phorbol
      12-myristate 13-acetate-induced translocation and accumulation of fully
      phosphorylated PKCgamma in the insoluble fraction, which could be rescued by
      coexpressing PDK1 kinase that normally triggers PKCgamma autophosphorylation. We
      propose that the SCA14 mutation V138E causes unfolding of the C1B domain and
      exposure of the C-terminus of the PKCgamma-V138E molecule, resulting in a
      decrease of functional kinase in the soluble fraction. Here, we show that the
      mutation V138E of the protein kinase C gamma (PKCgamma) C1B domain (PKCgamma
      V138E), which is implicated in spinocerebellar ataxia type 14, exhibits a
      partially unfolded C-terminus. This leads to unusually fast phorbol 12-myristate
      13-acetate-induced membrane translocation and accumulation of phosphorylated
      PKCgamma-V138E in the insoluble fraction, causing loss of the functional kinase.
      In contrast to general chaperones, coexpression of PKCgamma's 'natural
      chaperone', PDK1 kinase, could rescue the PKCgamma-V138E phenotype.

PMID- 24134141
TI  - Personalized dosimetry of 131I-rituximab radioimmunotherapy of non-hodgkin
      lymphoma defined by pharmacokinetics in bone marrow and blood.
AB  - PURPOSE: To report a comparison of SPECT/CT technique with standard blood-based
      dosimetry methodology in a cohort of non-Hodgkin lymphoma (NHL) patients treated
      with 131I-rituximab anti-CD20 chimeric monoclonal antibody. METHODOLOGY: Red
      marrow uptake was measured directly using serial quantitative whole-body imaging
      in conjunction with SPECT/CT in a cohort of 23 patients undergoing routine 131I
      rituximab radioimmunotherapy of NHL. Absorbed dose measurements were then
      compared with radiation doses calculated using standard peripheral blood counting
      methodology. RESULTS: Activity clearance from whole body of 88.7 hours measured
      by imaging 131I-rituximab was significantly slower (p<0.001) than the mean
      effective half-life clearance of 60.8 hours calculated from the sampling
      peripheral blood. The mean activity concentrations in bone marrow measured using
      SPECT/CT, and by blood sampling, extrapolated to the time of administration,
      were, however, concordant. The absorbed self-dose in red marrow, measured using
      imaging, was 1.02 Gy compared with the dose (0.81 Gy) calculated from blood
      sampling. Neutrophil toxicity correlated with absorbed dose by SPECT/CT imaging
      (p=0.01), whereas the blood sampling method demonstrated no correlation with any
      parameters of hematological toxicity. CONCLUSION: Radiation dose to red marrow
      from 131I-rituximab is inherently underestimated by standard indirect peripheral
      blood counting methods. Personalized marrow dosimetry by quantitative gamma
      imaging more accurately predicts of hemopoietic myelotoxicity by direct
      measurement of the bone marrow activity concentration of 131I-rituximab.

PMID- 24134142
TI  - The roles of topical negative pressure in deep burn wounds treated by dermal
      substitution.

PMID- 24134143
TI  - The association between blood alcohol content and cheerfulness, focus
      distraction, and sluggishness among young adults attending high school parties.
AB  - BACKGROUND: The belief that alcohol makes you cheerful is one of the main reasons
      for engaging in high-risk drinking, especially among young adults. The aim of the
      study was to investigate the association between blood alcohol content (BAC) and
      cheerfulness, focus distraction, and sluggishness among students attending high
      school parties. METHODS: Participants included 230 students attending high school
      parties. BAC, measured by use of a breath analyzer, self-reported cheerfulness
      (on a score from 0 to 16), focus distraction (score from 0 to 8), and
      sluggishness (score from 0 to 4) were assessed several times during the party.
      Data were analyzed by means of linear regression, including robust standard
      errors and stratified on sex. RESULTS: For girls, cheerfulness increased up to a
      BAC of 0.113 g% and decreased at higher BACs. At BACs of 0.020, 0.050, 0.100, and
      0.150 g% cheerfulness was 11.0 (95% confidence interval [CI]: 10.4 to 11.6), 12.4
      (95% CI: 11.8 to 12.9), 13.5 (95% CI: 13.0 to 14.0), and 13.1 (95% CI: 11.9 to
      14.4), respectively. For boys, the association was linear with an increase of
      0.18 points in cheerfulness (95% CI: 0.01 to 0.36) for every 0.010 g% increase in
      BAC. Focus distraction increased with increasing BAC: 0.22 (95% CI: 0.16 to 0.28)
      and 0.24 (95% CI: 0.14 to 0.33) points for girls and boys, respectively, per
      0.010 g% increase in BAC. The degree of sluggishness increased only slightly with
      increasing BAC with 0.02 (95% CI: 0.02 to 0.05) and 0.03 (95% CI: -0.01 to 0.07)
      points for every 0.010 g% increase in BAC for girls and boys, respectively.
      CONCLUSIONS: Cheerfulness increased up to a certain BAC value for girls, while it
      increased linearly for boys. Focus distraction increased with increasing BAC.

PMID- 24134144
TI  - Volatile organic compounds effective diffusion coefficients and fluxes estimation
      through two types of construction material.
AB  - Accumulation of volatile organic compounds (VOCs) that migrate inside buildings
      from underlying contaminated soils and groundwater poses human health risks. VOCs
      intrusion into buildings driven only by diffusion was reproduced by a laboratory
      scale experiment. Effective diffusion coefficients and fluxes of a group of
      selected chlorinated solvents and BTEX through two types of isolation material -
      that is, concrete (anhydrite screed) and geo-membrane - were estimated. The
      laboratory experiment indicated that the diffusive transfer of pollutants through
      sediments into indoor air of buildings cannot be prevented by building sealing
      material, but it could be attenuated to a certain degree by concrete and up to
      non-detectable levels by the geo-membrane. Effective diffusion coefficients
      through concrete and geo-membrane ranged from 3.17 * 10(-2) to 5.90 * 10(-5)
      cm(2) /s and from 5.47 * 10(-6) to 5.50 * 10(-8) cm(2) /s, respectively.
      PRACTICAL IMPLICATIONS: The vapor intrusion of volatile organic compounds (VOCs)
      into buildings has special relevance in human health risk assessment. Prediction
      of indoor air VOCs concentration by applying numerical or analytical models
      eventually fails due to the lack of input parameters, such as the VOCs effective
      diffusion coefficient through building material used as foundation or isolation
      material. Passive migration of VOCs from contaminated sites into indoor air
      through construction and isolation materials has not been extensively
      investigated. Our findings showed that the mass flux through building material is
      not negligible, but it could be reduced partly, and to a minimum, with the
      utilization of concrete and geo-membranes, respectively. As a result of our
      investigation, effective diffusion coefficients of BTEX and chlorinated solvents,
      as well as the correlation between specific compounds' parameters and the
      estimated effective diffusion coefficient, are provided.

PMID- 24134145
TI  - Rare atypical presentations in Type 2 lepra reaction: a case series.
AB  - OBJECTIVES: Type 2 lepra reaction is a Th2-mediated type III hypersensitivity
      reaction in leprosy, with a characteristic cutaneous manifestation in the form of
      erythema nodosum leprosum (ENL). We describe unusual presentations of Type 2
      lepra reaction in five patients. METHODS: Patient data and dermatological
      findings were analyzed in three men and two women diagnosed with Hansen's
      disease. RESULTS: Findings included multiple tender, polycyclic, necrotic lesions
      distributed over the face in one patient, and painful, fluid-filled lesions on
      both arms and lower limbs in another. The third patient showed erythematous,
      tender nodules, bullae, and necrotic ulcers over the back and upper and lower
      limbs. The fourth showed erythematous tender nodules over the face, neck, back,
      and extremities, predominantly in sun-exposed areas. The fifth revealed multiple
      erythematous, severely tender nodules and urticarial plaques mimicking those of
      Sweet's syndrome. Diagnosis of borderline or lepromatous leprosy with atypical
      Type 2 reaction were made in all cases. CONCLUSIONS: Type 2 lepra reactions are
      antigen antibody-mediated immune complex reactions that present with
      constitutional symptoms and ENL characterized by tender, erythematous, evanescent
      nodules mainly on the face, arms, and legs. Over 50% of lepromatous leprosy
      patients and 25% of borderline lepromatous leprosy patients experienced type 2
      lepra reactions prior to the advent of multi-drug therapy. Thalidomide is the
      drug of choice for severe atypical lepra reactions because of its anti-tumor
      necrosis factor-alpha action. Awareness of these atypical variants and prompt
      diagnosis and treatment are essential to prevent mortality and morbidity in
      potentially treatable patients.

PMID- 24134146
TI  - The role of cognitive reserve in cognitive aging: results from the neurocognitive
      study on aging.
AB  - The study tested the cognitive reserve hypothesis by quantifying cognitive
      reserve (CR) and subsequently determining its role in executive function and
      verbal episodic memory performance. A neuropsychological battery was administered
      to 383 Greek-Cypriot older adults. A multiple indicators multiple causes (MIMIC)
      latent construct was utilized to define CR incorporating three indicators: years
      of education, vocabulary, and reading performance. Findings from two structural
      equation models supported the moderating role of CR in reducing the direct
      negative effect of age on verbal episodic memory and on executive function. The
      study illustrates a parsimonious way of defining CR and provides empirical
      support for the CR hypothesis. 

PMID- 24134147
TI  - Emerging spectra of singular correlation matrices under small power-map
      deformations.
AB  - Correlation matrices are a standard tool in the analysis of the time evolution of
      complex systems in general and financial markets in particular. Yet most analysis
      assume stationarity of the underlying time series. This tends to be an assumption
      of varying and often dubious validity. The validity of the assumption improves as
      shorter time series are used. If many time series are used, this implies an
      analysis of highly singular correlation matrices. We attack this problem by using
      the so-called power map, which was introduced to reduce noise. Its nonlinearity
      breaks the degeneracy of the zero eigenvalues and we analyze the sensitivity of
      the so-emerging spectra to correlations. This sensitivity will be demonstrated
      for uncorrelated and correlated Wishart ensembles.

PMID- 24134148
TI  - Production of reactive oxygen species and wound-induced resistance in Arabidopsis
      thaliana against Botrytis cinerea are preceded and depend on a burst of calcium.
AB  - BACKGROUND: Wounded leaves of Arabidopsis thaliana produce reactive oxygen
      species (ROS) within minutes after wounding and become resistant to the
      pathogenic fungus Botrytis cinerea at a local level. This fast response of the
      plants to the wound is called wound-induced resistance (WIR). However the
      molecular mechanisms of this response and the signal cascade between the wound
      and ROS production are still largely unknown. Calcium is a conserved signal and
      it is involved in many abiotic stress responses in plants, furthermore, calcium
      pathways act very fast. RESULTS: The results of this study show that leaves
      treated with calcium channels inhibitors (verapamil) or calcium chelators
      (oxalate and EGTA) are impaired in ROS production. Moreover, leaves treated with
      verapamil, EGTA or oxalate were more susceptible to B. cinerea after wounding.
      The intracellular measurements of calcium changes indicated quick but transient
      calcium dynamics taking place few seconds after wounding in cells neighbouring
      the wound site. This change in the cytosolic calcium was followed in the same
      region by a more stable ROS burst. CONCLUSIONS: These data further extend our
      knowledge on the connection between wounding, calcium influx and ROS production.
      Moreover they provide for the first time the evidence that, following wounding,
      calcium changes precede a burst in ROS in the same location.

PMID- 24134149
TI  - In vitro metabolism of monensin A: microbial and human liver microsomes models.
AB  - 1. Monensin A, an important antibiotic ionophore that is primarily employed to
      treat coccidiosis, selectively complexes and transports sodium cations across
      lipid membranes and displays a variety of biological properties. 2. In this
      study, we evaluated the fungi Cunninghamella echinulata var. elegans ATCC 8688A,
      Cunninghamella elegans NRRL 1393 ATCC 10028B and human hepatic microsomes as CYP
      P450 models to investigate the in vitro metabolism of monensin A and compare the
      products with the metabolites produced in vivo. 3. Mass spectrometry analysis of
      the products from these model systems revealed the formation of three
      metabolites: 3-O-demethyl monensin A, 12-hydroxy monensin A and 12-hydroxy-3-O
      demethyl monensin A. We identified these products by tandem mass spectrometry and
      through comparison with the in vivo metabolites. 4. This analysis demonstrated
      that the model systems produce the same metabolites found in in vivo studies,
      thus they could be used to predict the metabolism of monensin A. Furthermore, we
      verified that liquid chromatography coupled to mass spectrometry is a powerful
      tool to study the in vitro metabolism of drugs, because it allows the successful
      identifications of several derivatives from different metabolic models.

PMID- 24134151
TI  - Fibroblast growth factor receptor 2: a therapeutic target in gastric cancer.
AB  - Gastric cancer remains a leading cause of cancer-related death in the world. FGF
      receptor 2 (FGFR2) is preferentially amplified and overexpressed in the diffuse
      type of gastric cancer. This review evaluates the expression and function of
      FGFR2 in gastric cancer, and analyzes the use of its inhibitors for gastric
      cancer therapy. This review also discusses the limitations of FGFR2-based
      therapy, and envisages future developments toward the clinical applications of
      FGFR2. 

PMID- 24134150
TI  - Gut microbiome perturbations induced by bacterial infection affect arsenic
      biotransformation.
AB  - Exposure to arsenic affects large human populations worldwide and has been
      associated with a long list of human diseases, including skin, bladder, lung, and
      liver cancers, diabetes, and cardiovascular disorders. In addition, there are
      large individual differences in susceptibility to arsenic-induced diseases, which
      are frequently associated with different patterns of arsenic metabolism. Several
      underlying mechanisms, such as genetic polymorphisms and epigenetics, have been
      proposed, as these factors closely impact the individuals' capacity to metabolize
      arsenic. In this context, the role of the gut microbiome in directly metabolizing
      arsenic and triggering systemic responses in diverse organs raises the
      possibility that perturbations of the gut microbial communities affect the
      spectrum of metabolized arsenic species and subsequent toxicological effects. In
      this study, we used an animal model with an altered gut microbiome induced by
      bacterial infection, 16S rRNA gene sequencing, and inductively coupled plasma
      mass spectrometry-based arsenic speciation to examine the effect of gut
      microbiome perturbations on the biotransformation of arsenic. Metagenomics
      sequencing revealed that bacterial infection significantly perturbed the gut
      microbiome composition in C57BL/6 mice, which in turn resulted in altered spectra
      of arsenic metabolites in urine, with inorganic arsenic species and methylated
      and thiolated arsenic being perturbed. These data clearly illustrated that gut
      microbiome phenotypes significantly affected arsenic metabolic reactions,
      including reduction, methylation, and thiolation. These findings improve our
      understanding of how infectious diseases and environmental exposure interact and
      may also provide novel insight regarding the gut microbiome composition as a new
      risk factor of individual susceptibility to environmental chemicals. 

PMID- 24134152
TI  - Thiopurines during pregnancy in inflammatory bowel disease: is there a risk for
      the (unborn) child?

PMID- 24134153
TI  - Acute kidney injury in acute liver failure: a review.
AB  - Acute liver failure is a rare and often devastating condition consequent on
      massive liver cell necrosis that frequently affects young, previously healthy
      individuals resulting in altered cognitive function, coagulopathy and peripheral
      vasodilation. These patients frequently develop concurrent acute kidney injury
      (AKI). This abrupt and sustained decline in renal function, through a number of
      pathogenic mechanisms such as renal hypoperfusion, direct drug-induced
      nephrotoxicity or sepsis/systemic inflammatory response contributes to increased
      morbidity and is strongly associated with a worse prognosis. Improved
      understanding of the pathophysiology AKI in the context of acute liver failure
      may be beneficial in a number of areas; the development of new and sensitive
      biomarkers of renal dysfunction, refining prognosis and organ allocation, and
      ultimately leading to the development of novel treatment strategies, these issues
      are discussed in more detail in this expert review. 

PMID- 24134154
TI  - Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel
      syndrome subjects.
AB  - Loss of intestinal absorptive capacity from congenital defect, surgical resection
      or mucosal disease results in short bowel syndrome (SBS)-associated intestinal
      failure. In the past, few medical management options were available besides
      dietary modification, controlling diarrhea or high stomal output, and providing
      parenteral fluid, electrolyte and nutrient support (parenteral support). Recent
      research on strategies to enhance the intestinal absorptive capacity focused on
      glucagon-like peptide-2, an intestinotrophic hormone that has been shown to
      increase the villus height and crypt depth, and decrease gastric motility and
      intestinal secretory losses. STEPS is a Phase III randomized double-blinded
      controlled trial in which teduglutide, a recombinant analog of glucagon-like
      peptide-2, or placebo was given subcutaneously to SBS patients for 24 weeks. A
      clinically meaningful response, defined as a 20-100% reduction in parenteral
      support volume, was achieved in 63% of the treatment group compared with 30% in
      the placebo group (p = 0.002) without an increase in serious side effects.
      Teduglutide offers a new targeted approach to SBS-associated intestinal failure
      management. Its specific role in clinical practice remains to be evaluated. 

PMID- 24134155
TI  - Milk thistle to treat non-alcoholic fatty liver disease: dream or reality?

PMID- 24134156
TI  - Comparison of salivary collection and processing methods for quantitative HHV-8
      detection.
AB  - OBJECTIVES: Saliva is a proved diagnostic fluid for the qualitative detection of
      infectious agents, but the accuracy of viral load determinations is unknown.
      Stabilising fluids impede nucleic acid degradation, compared with collection onto
      ice and then freezing, and we have shown that the DNA Genotek P-021 prototype kit
      (P-021) can produce high-quality DNA after 14 months of storage at room
      temperature. Here we evaluate the quantitative capability of 10
      collection/processing methods. METHODS: Unstimulated whole mouth fluid was spiked
      with a mixture of HHV-8 cloned constructs, 10-fold serial dilutions were
      produced, and samples were extracted and then examined with quantitative PCR
      (qPCR). Calibration curves were compared by linear regression and qPCR dynamics.
      RESULTS: All methods extracted with commercial spin columns produced linear
      calibration curves with large dynamic range and gave accurate viral loads.
      Ethanol precipitation of the P-021 does not produce a linear standard curve, and
      virus is lost in the cell pellet. DNA extractions from the P-021 using commercial
      spin columns produced linear standard curves with wide dynamic range and
      excellent limit of detection. CONCLUSION: When extracted with spin columns, the P
      021 enables accurate viral loads down to 23 copies MUl(-1) DNA. The quantitative
      and long-term storage capability of this system makes it ideal for study of
      salivary DNA viruses in resource-poor settings.

PMID- 24134157
TI  - HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43
      hemichannel-dependent mechanism.
AB  - Human immunodeficiency virus-1 (HIV) is a public health issue and a major
      complication of the disease is NeuroAIDS. In vivo, microglia/macrophages are the
      main cells infected. However, a low but significant number of HIV-infected
      astrocytes has also been detected, but their role in the pathogenesis of
      NeuroAIDS is not well understood. Our previous data indicate that gap junction
      channels amplify toxicity from few HIV-infected into uninfected astrocytes. Now,
      we demonstrated that HIV infection of astrocytes results in the opening of
      connexin43 hemichannels (HCs). HIV-induced opening of connexin43 HCs resulted in
      dysregulated secretion of dickkopf-1 protein (DKK1, a soluble wnt pathway
      inhibitor). Treatment of mixed cultures of neurons and astrocytes with DKK1, in
      the absence of HIV infection, resulted in the collapse of neuronal processes. HIV
      infection of mixed cultures of human neurons and astrocytes also resulted in the
      collapse of neuronal processes through a DKK1-dependent mechanism. In addition,
      dysregulated DKK1 expression in astrocytes was observed in human brain tissue
      sections of individuals with HIV encephalitis as compared to tissue sections from
      uninfected individuals. Thus, we demonstrated that HIV infection of astrocytes
      induces dysregulation of DKK1 by a HC-dependent mechanism that contributes to the
      brain pathogenesis observed in HIV-infected individuals. Our studies demonstrated
      that HIV infection of astrocytes, despite minimal replication and a low number of
      infected cells, induces dysregulation of DKK1 secretion by a Cx43 hemichannel
      (HC)-dependent mechanism. Enhanced DKK1 secretion in response to HIV infection of
      glial cells compromised formation and stability of neuronal processes, similar to
      the synaptic compromise observed in HIV-infected individuals. In addition,
      analysis of human brain tissue sections obtained from encephalitic individuals
      also shows enhanced expression of DKK1 in astrocytes. Our data provide a novel
      mechanism by which HIV infection of glial cells participate in the pathogenesis
      of brain dysfunction observed in HIV-infected individuals. LRP5 = Low-density
      lipoprotein receptor-related protein 5.

PMID- 24134158
TI  - Feature tracking measurement of dyssynchrony from cardiovascular magnetic
      resonance cine acquisitions: comparison with echocardiographic speckle tracking.
AB  - BACKGROUND: Analysis of left ventricular (LV) mechanical dyssynchrony may provide
      incremental prognostic information regarding cardiac resynchronization therapy
      (CRT) response in addition to QRS width alone. Our objective was to quantify LV
      dyssynchrony using feature tracking post processing of routine cardiovascular
      magnetic resonance (CMR) cine acquisitions (FT-CMR) in comparison to speckle
      tracking echocardiography. METHODS: We studied 72 consecutive patients who had
      both steady-state free precession CMR and echocardiography. Mid-LV short axis CMR
      cines were analyzed using FT-CMR software and compared with echocardiographic
      speckle tracking radial dyssynchrony (time difference between the anteroseptal
      and posterior wall peak strain). RESULTS: Radial dyssynchrony analysis was
      possible by FT-CMR in all patients, and in 67 (93%) by echocardiography.
      Dyssynchrony by FT-CMR and speckle tracking showed limits of agreement of strain
      delays of +/- 84 ms. These were large (up to 100% or more) relative to the small
      mean delays measured in more synchronous patients, but acceptable (mainly <25%)
      in those with mean delays of >200 ms. Radial dyssynchrony was significantly
      greater in wide QRS patients than narrow QRS patients by both FT-CMR (radial
      strain delay 230 +/- 94 vs. 77 +/- 92* ms) and speckle tracking (radial strain
      delay 242 +/- 101 vs. 75 +/- 88* ms, all *p < 0.001). CONCLUSIONS: FT-CMR
      delivered measurements of radial dyssynchrony from CMR cine acquisitions which,
      at least for the patients with more marked dyssynchrony, showed reasonable
      agreement with those from speckle tracking echocardiography. The clinical
      usefulness of the method, for example in predicting prognosis in CRT patients,
      remains to be investigated.

PMID- 24134159
TI  - The milspouse battle rhythm: communicating resilience throughout the deployment
      cycle.
AB  - Military spouses (milspouses) enact resilience through communication before,
      during, and after military deployments. Based on an organizing framework of
      resilience processes ( Buzzanell, 2010 ), this study examined milspouses'
      communicative construction of resilience during an increasingly rapid military
      deployment cycle. Narratives from in-depth interviews with military spouses (n =
      24) revealed how resilience is achieved through communication seeking to
      reconcile the often contradictory realities of milspouses who endure physical,
      psychological, and social difficulties due to prolonged separations from their
      partners. 

PMID- 24134160
TI  - Intracellular and extracellular adenosine triphosphate in regulation of insulin
      secretion from pancreatic beta cells (beta).
AB  - Adenosine triphosphate (ATP) synthesis and release in mitochondria play critical
      roles in regulating insulin secretion in pancreatic beta cells. Mitochondrial
      dysfunction is mainly characterized by a decrease in ATP production, which is a
      central event in the progression of pancreatic beta cell dysfunction and
      diabetes. ATP has been demonstrated to regulate insulin secretion via several
      pathways: (i) Intracellular ATP directly closes ATP-sensitive potassium channel
      to open L-type calcium channel, leading to an increase in free cytosolic calcium
      levels and exocytosis of insulin granules; (ii) A decrease in ATP production is
      always associated with an increase in production of reactive oxygen species,
      which exerts deleterious effects on pancreatic beta cell survival and insulin
      secretion; and (iii) ATP can be co-secreted with insulin from pancreatic beta
      cells, and the released ATP functions as an autocrine signal to modulate insulin
      secretory process via P2 receptors on the cell membrane. In this review, the
      recent findings regarding the role and mechanism of ATP synthesis and release in
      regulation of insulin secretion from pancreatic beta cells will be summarized and
      discussed. 

PMID- 24134161
TI  - Diffuse dermal melanocytosis in two patients with Sandhoff disease and
      mucopolysaccharidosis VI.
AB  - Dermal melanocytosis (DM) is described as the presence of ectopic melanocytes in
      the dermis and could be a normal cutaneous finding. However, diffuse DM or
      extensive Mongolian spots must be considered as an early sign of neurometabolic
      diseases, in particular lysosomal storage disorders. The presence of extensive DM
      should alert the physician to the presence of such disorders, making early
      diagnosis possible. We describe for the first time the presence of DM in two
      patients with Sandhoff disease and mucopolysaccharidosis VI. 

PMID- 24134162
TI  - Site-specific imaging of elemental steps in dehydration of diols on TiO(2)(110).
AB  - Scanning tunneling microscopy is employed to follow elemental steps in conversion
      of ethylene glycol and 1,3-propylene glycol on partially reduced TiO2(110) as a
      function of temperature. Mechanistic details about the observed processes are
      corroborated by density functional theory calculations. The use of these two diol
      reactants allows us to compare and contrast the chemistries of two functionally
      similar molecules with different steric constraints, thereby allowing us to
      understand how molecular geometry may influence the observed chemical reactivity.
      We find that both glycols initially adsorb on Ti sites, where a dynamic
      equilibrium between molecularly bound and deprotonated species is observed. As
      the diols start to diffuse along the Ti rows above 230 K, they irreversibly
      dissociate upon encountering bridging oxygen vacancies. Surprisingly, two
      dissociation pathways, one via O-H and the other via C-O bond scission, are
      observed. Theoretical calculations suggest that the differences in the C-O/O-H
      bond breaking processes are the result of steric factors enforced upon the diols
      by the second Ti-bound OH group. Above ~400 K, a new stable intermediate centered
      on the bridging oxygen (Ob) row is observed. Combined experimental and
      theoretical evidence shows that this intermediate is most likely a new dioxo
      species. Further annealing leads to sequential C-Ob bond cleavage and alkene
      desorption above ~500 K. Simulations demonstrate that the sequential C-Ob bond
      breaking process follows a homolytic diradical pathway, with the first C-Ob bond
      breaking event accompanied with a nonadiabatic electron transfer within the
      TiO2(110) substrate. 

PMID- 24134163
TI  - Ghrelin receptor-knockout mice display alterations in circadian rhythms of
      activity and feeding under constant lighting conditions.
AB  - Ghrelin is an orexigenic hormone produced by the stomach. Ghrelin, however, may
      also be a modulator of the circadian system given that ghrelin receptors are
      expressed in the master clock, the suprachiasmatic nucleus (SCN) and several
      outputs of this region. To investigate this, we performed analyses of running
      wheel activity and neuronal activation in wild type (WT) and growth hormone
      secretagogue receptor-knockout (GHSR-KO) mice under various lighting conditions.
      GHSR-KO and WT mice were maintained under constant dark (DD) or constant light
      (LL) with ad libitum access to food before being placed on a schedule of
      temporally restricted access to food (4 h/day) for 2 weeks. There were no
      differences between KO and WT mice in free-running period under DD, but GHSR-KO
      mice required more days to develop a high level of food anticipatory activity,
      and this was lower than that observed in WT mice. Under LL, GHSR-KO mice showed
      greater activity overall, lengthening of their circadian period, and more
      resistance to the disorganisational effects of LL. Furthermore, GHSR-KO mice
      showed greater activity overall, and greater activity in anticipation of a
      scheduled meal under LL. These behavioral effects were not correlated with
      changes in the circadian expression of the Fos, Per1 or Per2 proteins under any
      lighting conditions. These results suggest that the ghrelin receptor plays a role
      in modulating the activity of the circadian system under normal conditions and
      under restricted feeding schedules, but does so through mechanisms that remain to
      be determined. 

PMID- 24134165
TI  - Institutional racism, neighborhood factors, stress, and preterm birth.
AB  - OBJECTIVE: Racial/ethnic disparities in the risk of preterm birth may be
      explained by various factors, and previous studies are limited in examining the
      role of institutional racism. This study focused on the following questions: what
      is the association between preterm birth and institutional racism as measured by
      residential racial segregation (geographic separation by race) and redlining
      (black-white disparity in mortgage loan denial); and what is the association
      between preterm birth and reported stress, discrimination, and neighborhood
      quality. DESIGN: We used data from a clinic-based sample of pregnant women (n =
      3462) participating in a stress and pregnancy study conducted from 1999 to 2004
      in Philadelphia, PA (USA). We linked data from the 2000 US Census and Home
      Mortgage Disclosure Act (HMDA) data from 1999 to 2004 and developed measures of
      residential redlining and segregation. RESULTS: Among the entire population,
      there was an increased risk for preterm birth among women who were older,
      unmarried, tobacco users, higher number of previous births, high levels of
      experiences of everyday discrimination, owned their homes, lived in nonredlined
      areas, and areas with high levels of segregation measured by the isolation index.
      Among black women, living in a redlined area (where blacks were more likely to be
      denied mortgage loans compared to whites) was moderately associated with a
      decreased risk of preterm birth (aRR = 0.8, 95% CI: 0.6, 0.99). CONCLUSION:
      Residential redlining as a form institutional racism and neighborhood
      characteristic may be important for understanding racial/ethnic disparities in
      pregnancy and preterm birth.

PMID- 24134164
TI  - HIV-1 and alcohol: interactions in the central nervous system.
AB  - The use of alcohol has been associated with both an increased risk of acquisition
      of HIV-1 infection and an increased rate of disease progression among those
      already infected by the virus. The potential for alcohol to exacerbate the
      effects of HIV infection is especially important in the central nervous system
      (CNS) because this area is vulnerable to the combined effects of alcohol and HIV
      infection. The effects of alcohol on glial cells are mediated through receptors
      such as Toll-like receptor 4 and N-methyl-d-aspartate receptor. This causes the
      activation of signaling molecules such as interleukin-1 receptor-associated
      kinase and various members of the P38 mitogen-activated protein kinase family and
      subsequent activation of transcription factors such as nuclear factor-kappa beta
      and activator protein 1. The eventual outcome is an increase in pro-inflammatory
      cytokine production by glial cells. Alcohol also induces higher levels of NADPH
      oxidase in glial cells, which leads to an increased production of reactive oxygen
      species (ROS). Viral invasion of the CNS occurs early after infection, and HIV
      proteins have also been demonstrated to increase levels of pro-inflammatory
      cytokines and ROS in glial cells through activation of some of the same pathways
      activated by alcohol. Both cell culture systems and animal models have
      demonstrated that concomitant exposure to alcohol and HIV/HIV proteins results in
      increased levels of expression of pro-inflammatory cytokines such as interleukin
      1 beta and tumor necrosis factor-alpha, along with increased levels of oxidative
      stress. Clinical studies also suggest that alcohol exacerbates the CNS effects of
      HIV-1 infection. This review focuses on the mechanisms by which alcohol causes
      increased CNS damage in HIV-1 infection. 

PMID- 24134167
TI  - What is quality of medicines?

PMID- 24134166
TI  - An analysis of oligomerization interfaces in transmembrane proteins.
AB  - BACKGROUND: The amount of transmembrane protein (TM) structures solved to date is
      now large enough to attempt large scale analyses. In particular, extensive
      studies of oligomeric interfaces in the transmembrane region are now possible.
      RESULTS: We have compiled the first fully comprehensive set of validated
      transmembrane protein interfaces in order to study their features and assess what
      differentiates them from their soluble counterparts. CONCLUSIONS: The general
      features of TM interfaces do not differ much from those of soluble proteins: they
      are large, tightly packed and possess many interface core residues. In our set,
      membrane lipids were not found to significantly mediate protein-protein
      interfaces. Although no G protein-coupled receptor (GPCR) was included in the
      validated set, we analyzed the crystallographic dimerization interfaces proposed
      in the literature. We found that the putative dimer interfaces proposed for class
      A GPCRs do not show the usual patterns of stable biological interfaces, neither
      in terms of evolution nor of packing, thus they likely correspond to crystal
      interfaces. We cannot however rule out the possibility that they constitute
      transient or weak interfaces. In contrast we do observe a clear signature of
      biological interface for the proposed dimer of the class F human Smoothened
      receptor.

PMID- 24134168
TI  - Functional bowel symptoms and diet.
AB  - It is well recognised that ingestion of food is a trigger for functional bowel
      symptoms, particularly those associated with irritable bowel syndrome (IBS).
      Patients often use manipulation of diet as a means of controlling symptoms.
      Despite description of multiple dietary methods, few have scientific backing or
      quality evidence of efficacy. One approach is to define how specific food
      components influence the pathophysiology of IBS and then rationally design
      dietary approaches. For example, short-chain poorly absorbed carbohydrates
      (fermentable oligo-, di- and mono-saccharides and polyols (FODMAP)) cause luminal
      distension, which is a major stimulus for the development of symptoms in patients
      with visceral hypersensitivity. By determining food content of FODMAP, a diet in
      which foods low in FODMAP are favoured over those high in FODMAP can be designed.
      Observational, comparative and randomised controlled treatment and rechallenge
      studies have shown that such an approach is efficacious in the majority of
      patients with IBS. The low FODMAP diet is now the primary dietary therapy for
      such patients. Similar approaches can be applied to other food components,
      including proteins (such as gluten), fats and natural bioactive food chemicals.
      Such approaches have suggestions of efficacy, but the evidence base remains
      underdeveloped. An additional and important consideration for any dietary therapy
      is its nutritional adequacy and potential adverse health effects. Dietary
      manipulation is now a key management strategy in patients with functional bowel
      symptoms. Future well-designed interventional studies will lead to refinement of
      dietary approaches taken and to a better understanding of their long-term safety.

PMID- 24134169
TI  - Practical aspects of telehealth: set-up and preparation for video consultations.
AB  - The third in a series of articles about the practical aspects of telehealth, this
      paper gives guidance on suitable setup for video consultations, including layout
      of rooms, managing sound and image quality, scheduling, testing and best practice
      in telehealth videoconferencing. 

PMID- 24134170
TI  - Peripheral T-cell lymphoma mimicking 5-aminosalicylate hypersensitivity in
      ulcerative colitis.
AB  - 5-aminosalicylates (5-ASA) remain an important strategy in the induction and
      maintenance of remission of inflammatory bowel diseases especially in ulcerative
      colitis. The prototypical drug of this class, sulfasalazine is generally well
      tolerated with severe hypersensitivity reactions and hepatotoxicity also
      described within the literature. When approaching a patient with an adverse
      reaction to 5-ASA, it can be difficult to differentiate clinically between a
      sulfa allergy versus a 5-ASA allergy versus a malignancy. We report on a case
      with initial signs and symptoms suggestive of a sulfa/5-ASA allergy that was
      subsequently found to be malignant in nature. 

PMID- 24134171
TI  - Computed tomography in patients with abdominal pain and diarrhoea: does the
      benefit outweigh the drawbacks?
AB  - The role of computed tomography (CT) in the evaluation of abdominal pain is well
      established. However, concern exists in regard to procedure-related radiation
      levels, contrast-medium toxicity and costs. We sought to determine whether the
      use of abdominal CT caused major changes in the management of patients who had
      abdominal pain and diarrhoea. We reviewed all abdominal CT examinations that were
      performed at our hospital from October through December 2010. We selected 574
      scans that had been performed in patients who presented with or without
      diarrhoea. We examined the selected medical records to determine whether the CT
      scan changed patients' management. A scan was considered to be management
      changing if a decisive intervention occurred on the basis of the scan results.
      Among 124 scans in patients with diarrhoea and 450 scans in patients without
      diarrhoea, the scan results changed management in 13 of the patients with
      diarrhoea (11%) and in 233 of those without diarrhoea (52%) (P < 0.001). When
      management changed, the changes resulted from findings unrelated to diarrhoea.
      Despite its defined role in the assessment of abdominal pain, CT of patients that
      also had diarrhoea seldom caused a major change in management. The probability of
      CT causing such a change does not outweigh the cost, radiation risk or potential
      for contrast-induced nephropathy.

PMID- 24134172
TI  - Systemic capillary leak syndrome: recognition prevents morbidity and mortality.
AB  - Idiopathic systemic capillary leak syndrome (SCLS) is extremely rare but carries
      a high morbidity and mortality. The diagnosis is made clinically by a classic
      triad of hypotension, hypoalbuminaemia and haemoconcentration. There have been
      recent advances in understanding the pathophysiological basis for SCLS and in
      effective prophylaxis. We report a case of SCLS to increase awareness of the
      condition and to highlight the benefits of prophylactic intravenous
      immunoglobulin in this condition. 

PMID- 24134173
TI  - Prolonged vitamin D intoxication: presentation, pathogenesis and progress.
AB  - Vitamin D toxicity from unactivated vitamin D (calciferol) therapy is currently a
      rare cause of hypercalcaemia. However, the frequency of this event may increase
      as high-dose unactivated vitamin D preparations become available. Prolonged
      vitamin D toxicity can cause reversible hypercalcaemia and partially reversible
      renal impairment. Parathyroid hormone may not be suppressed with unactivated
      vitamin D toxicity, especially if renal disease coexists. 

PMID- 24134174
TI  - Are doctors the structural weakness in the e-health building?
AB  - Progressive evaluations by the Organization for Economic Co-operation and
      Development (OECD) demonstrate that health care is now or becoming unaffordable.
      This means nations must change the way they manage health care. The costly nature
      of health care in most nations, as a percentage of Gross Domestic Product (GDP)
      seems independent of the national funding models. Increasing evidence is
      demonstrating that the lack of involvement by clinicians (doctors, nurses,
      pharmacists, ancillary care and patients) in e-health projects is a major factor
      for the costly failures of many of these projects. The essential change in focus
      required to improve healthcare delivery using e-health technologies has to be on
      clinical care. To achieve this change clinicians must be involved at all stages
      of e-health implementations. From a clinicians perspective medicine is not a
      business. Our business is clinical medicine and e-health must be focussed on
      clinical decision making. This paper views the roles of physicians in e-health
      structural reforms. 

PMID- 24134175
TI  - Deep vein thrombosis in association with acute intravascular haemolysis in
      glucose-6-phosphate dehydrogenase deficiency: a unique case.

PMID- 24134176
TI  - Ceftriaxone-associated urolithiasis treated with ureteral stenting and
      extracorporeal shock wave lithotripsy.

PMID- 24134177
TI  - Venous thromboprophylaxis audit in two Queensland hospitals.

PMID- 24134178
TI  - A vaccine against tick-borne encephalitis is available in Australia.

PMID- 24134179
TI  - Identification of host and viral factors involved in a dissimilar resolution of a
      hepatitis C virus infection.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) transmission from a chronic patient to
      a susceptible individual is a good opportunity to study viral and host factors
      that may influence the natural course of hepatitis C infection towards either
      spontaneous recovery or chronicity. To compare a documented case of a bottleneck
      event in the sexual transmission of HCV from a chronically infected patient to a
      recipient host that cleared infection. METHODS: Host genetic components such as
      Class I and II HLA and IL28B polymorphism (rs12979860 SNPs) were identified by
      direct sequencing and LightMix analysis, respectively. Deep nucleotide sequence
      analysis of quasispecies complexity was performed using massive pyrosequencing
      platform (454 GS-FLX), and the CD4 specific immune response was characterized by
      ELISPOT. RESULTS AND CONCLUSIONS: Sequencing analysis and CD4 response
      highlighted several NS3-helicase domains in which an interplay between amino acid
      variability and CD4 immune response might have contributed either to chronicity
      in the donor patient or to viral clearance in the receptor (newly infected)
      patient.

PMID- 24134180
TI  - Reducing the pain of intramuscular benzathine penicillin injections in the
      rheumatic fever population of Counties Manukau District Health Board.
AB  - AIM: To evaluate the effectiveness of lignocaine and a vibrating device with cold
      pack (Buzzy) for pain management of intramuscular (IM) benzathine penicillin
      injections in the rheumatic fever (RF) population of Counties Manukau District
      Health Board (CMDHB). METHODS: Four hundred and five RF patients receiving four
      weekly injections in the CMDHB region were offered 0.25 mL of lignocaine 2% and
      Buzzy for pain management of their injections. The lignocaine was mixed in with
      the benzathine penicillin prior to administration. A pre and post survey assessed
      pain scores during, 2-min and 1-h post administration and the following day.
      Questions assessing fear were also included. RESULTS: In total 49% of patients
      responded to the survey. There were 118 surveys paired pre and post intervention.
      Pain at injection delivery and fear scores were higher for participants <=13
      years of age. Overall pain scores were significantly reduced over all four time
      points. There was also a significant reduction in fear of the injections.
      Lignocaine and Buzzy resulted in a greater reduction in pain than lignocaine
      alone, only when the injection was being administered to those <=13 years. After
      five months, a file audit showed that 66% of all RF patients of CMDHB were
      choosing to use lignocaine and 43% were choosing to use Buzzy. In total, 71% of
      all RF patients were choosing one or both of these analgesic interventions.
      CONCLUSION: This study demonstrates a clinically important reduction in the
      subjective experience of pain when two analgesic interventions were offered with
      IM delivery of benzathine penicillin. These pain reduction strategies have been
      popular in the RF population of CMDHB with a 71% uptake and a corresponding
      reduction in pain and fear.

PMID- 24134181
TI  - Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult
      volunteers with mild or moderate renal impairment.
AB  - AIMS: To evaluate the pharmacokinetics and pharmacodynamics following a single
      dose of liposomal mifamurtide (L-MTP-PE, MEPACT((r))) in adult subjects with mild
      (calculated creatinine clearance [CLcr ] of 50-80 ml min(-1)) or moderate (CLcr
      30-50 ml min(-1)) renal impairment in comparison with age-, weight- and gender
      matched healthy subjects with normal renal function (CLcr >80 ml min(-1)).
      METHODS: Subjects received a 4 mg dose of liposomal mifamurtide via 1 h
      intravenous infusion. Blood samples were collected over 72 h for analysis of
      plasma pharmacokinetics of total and non-liposome-associated (free) mifamurtide
      and assessment of pharmacodynamics (changes in serum interleukin-6 [IL-6], tumour
      necrosis factor-alpha [TNF-alpha], C-reactive protein [CRP]). RESULTS: Thirty
      three subjects were enrolled: nine with mild renal impairment, eight with
      moderate renal impairment and 16 healthy subjects. Geometric mean (%CV) AUCinf
      for total mifamurtide was 89.5 (58.1), 94.8 (27.8), 85.1 (29.0), 95.4 (18.1) nM h
      in the mild renal impairment, mild-matched healthy subject, moderate renal
      impairment and moderate-matched healthy subject groups, respectively. Mifamurtide
      clearance was not correlated with CLcr, estimated glomerular filtration rate or
      iohexol clearance (all r(2) < 0.01). AUCinf of free mifamurtide was similar
      across the renal function groups. There were no readily apparent differences in
      serum pharmacodynamic effect parameters (baseline-adjusted AUEClast for IL-6 and
      TNF-alpha and Emax for CRP) between the renal function groups. No subjects
      reported grade >=3 or serious adverse events. CONCLUSIONS: Mild or moderate renal
      impairment does not alter the clinical pharmacokinetics or pharmacodynamics of
      mifamurtide. No dose modifications appear necessary for these patients based on
      clinical pharmacologic considerations.

PMID- 24134182
TI  - A simple microfluidic strategy for cell migration assay in an in vitro wound
      healing model.
AB  - In vitro scratch wound assays are commonly used strategies to measure cell repair
      rate, facilitating the study of cell migration, tissue reorganization, and cell
      division. This work presented a simple and novel microfluidic device that allowed
      a quantitative investigation of the cell migration and cell proliferation
      behaviors in an in vitro wound-healing model, especially focused on the scratch
      assay. The microfluidic device is composed of four units, which include cell
      growth regions and cell-free regions created by micropillars. Using this device,
      we evaluated the proliferation and migration process of human gastric epithelial
      cells in the presence of different concentrations of the epidermal growth factor,
      and investigated the migration behavior of mesenchymal stem cells toward tumor
      cells as well. This approach has the unique capability to create localized cell
      free regions in parallel, and facilitate quantitative research on cell migration
      in the wound-healing process, providing a powerful platform for elucidating the
      mechanism of cell migration in regeneration medicine. 

PMID- 24134183
TI  - How tablet technology is going to change cooperative diagnosis in the cytology e
      laboratory.

PMID- 24134184
TI  - Spanning boundaries into remote communities: an exploration of experiences with
      telehealth chronic disease self-management programs in rural northern ontario,
      Canada.
AB  - BACKGROUND: In rural and remote settings, providing education programs for
      chronic conditions can be challenging because of the limited access and
      availability of healthcare services. The purpose of this study was to explore the
      experiences of participants in a chronic disease self-management program via
      telehealth (tele-CDSMP) and to identify facilitators and barriers to inform
      future tele-CDSMP delivery models. MATERIALS AND METHODS: Nineteen tele-CDSMP
      courses were delivered to 13 Northern Ontario (Canada) communities. Two types of
      group were delivered: (1) single telehealth site (one community formed a self
      management group linked to program leaders via telehealth) and (2) multiple
      telehealth sites (several remote communities were linked to each other and
      program leaders via telehealth). Following the completion of the courses,
      participants were invited to partake in a focus group. RESULTS: Overall, 44
      people participated in the focus groups. Four main themes were identified by tele
      CDSMP participants related to the overall experience of the program: (1) bridging
      the access gap, (2) importance of group dynamics, (3) importance of strong
      leaders, and (4) preference for extended session time. Key barriers were related
      to transportation, lack of session time, and access to Internet-based resources.
      The main facilitators were having strong program leaders, encouraging the
      development of group identity, and providing enough time to be comfortable with
      technology. CONCLUSIONS: Our findings suggest overall the tele-CDSMP was a
      positive experience for participants and that tele-CDSMPs are an effective option
      to increasing access to more geographically isolated communities.

PMID- 24134185
TI  - Germline mutations and genotype-phenotype correlations in patients with
      apparently sporadic pheochromocytoma/paraganglioma in Korea.
AB  - The aim of our study was to assess the frequency of germline mutations and
      develop the genetic testing strategy in patients with apparently sporadic
      pheochromocytoma/paraganglioma (PPGL) in Korea. We included 53 patients diagnosed
      with non-syndromic PPGL without a family history of PPGLs in three referral
      centers from 2004 to 2011. Succinate dehydrogenase complex B (SDHB), SDHD, Von
      Hippel-Lindau (VHL), and rearranged during transfection (RET) genes were examined
      by direct sequencing and multiple ligation-dependent probe amplification. The
      study patients were composed of 26 men and 27 women, and mean age was 50.1 +/-
      13.5 years. The frequency of germline mutations was 13.2% (7/53): RET (n = 2),
      VHL (n = 1), SDHB (n = 2), and SDHD (n = 2). Six of seven mutation carriers were
      diagnosed before the age of 50. One of two patients harboring an SDHB mutation
      had malignant PPGLs. One patient with multifocal head and neck paraganglioma
      (PGL) and pheochromocytoma (PHEO) carried a SDHD mutation. The carriers of
      germline mutations in patients with apparently sporadic PPGL were 13.2% in our
      study. We recommend genetic testing in patients below 50 years and SDHD genetic
      testing in patients with multifocal PPGLs. In malignant PPGLs, SDHB genetic
      testing may be performed. 

PMID- 24134186
TI  - Galectin-7, induced by cis-urocanic acid and ultraviolet B irradiation, down
      modulates cytokine production by T lymphocytes.
AB  - Urocanic acid (UCA) is an epidermal chromophore that undergoes trans to cis
      isomerization after UVB irradiation. cis-UCA is a potent inhibitor of cutaneous
      acquired immunity. The aim of this study was to explore the genes, which are
      upregulated by cis-UCA in normal human epidermal keratinocytes (NHEK) and
      investigated its role in vitro using human T-lymphocyte cell line, Jurkat cells.
      DNA microarray analysis and real-time PCR investigation revealed that cis-UCA,
      not trans-UCA, increased the expression of a gene encoding a beta-galactoside
      binding lectin, galectin-7, LGALS7B. Immunohistochemical study demonstrated that
      galectin-7 was highly expressed in the epidermis in the patients with actinic
      keratosis. Galectin-7 administration upregulated apoptosis and inhibited the
      expression of interleukin-2 (IL2) and interferon-gamma (IFNG) mRNA in Jurkat
      cells. Taken together, galectin-7 may play important roles in downregulating the
      functions of T lymphocytes after UVB irradiation and can be developed into novel
      immunosuppressive therapies for inflammatory skin diseases. 

PMID- 24134187
TI  - Replication across regioisomeric ethylated thymidine lesions by purified DNA
      polymerases.
AB  - Causal links exist between smoking cigarettes and cancer development. Some
      genotoxic agents in cigarette smoke are capable of alkylating nucleobases in DNA,
      and higher levels of ethylated DNA lesions were observed in smokers than in
      nonsmokers. In this study, we examined comprehensively how the regioisomeric O(2)
      , N3-, and O(4)-ethylthymidine (O(2)-, N3-, and O(4)-EtdT, respectively) perturb
      DNA replication mediated by purified human DNA polymerases (hPols) eta, kappa,
      and iota, yeast DNA polymerase zeta (yPol zeta), and the exonuclease-free Klenow
      fragment (Kf(-)) of Escherichia coli DNA polymerase I. Our results showed that
      hPol eta and Kf(-) could bypass all three lesions and generate full-length
      replication products, whereas hPol iota stalled after inserting a single
      nucleotide opposite the lesions. Bypass conducted by hPol kappa and yPol zeta
      differed markedly among the three lesions. Consistent with its known ability to
      efficiently bypass the minor groove N(2)-substituted 2'-deoxyguanosine lesions,
      hPol kappa was able to bypass O(2)-EtdT, though it experienced great difficulty
      in bypassing N3-EtdT and O(4)-EtdT. yPol zeta was only modestly blocked by O(4)
      EtdT, but the polymerase was strongly hindered by O(2)-EtdT and N3-EtdT. LC-MS/MS
      analysis of the replication products revealed that DNA synthesis opposite O(4)
      EtdT was highly error-prone, with dGMP being preferentially inserted, while the
      presence of O(2)-EtdT and N3-EtdT in template DNA directed substantial
      frequencies of misincorporation of dGMP and, for hPol iota and Kf(-), dTMP. Thus,
      our results suggested that O(2)-EtdT and N3-EtdT may also contribute to the AT ->
      TA and AT -> GC mutations observed in cells and tissues of animals exposed to
      ethylating agents. 

PMID- 24134189
TI  - Carbon dioxide alters the Hoffmann reflex independent of hydrogen ions.
AB  - The purpose of this study was to examine the effect of changes in capillary blood
      pH on the resting soleus Hoffmann (H) reflex in the intact human. H-max size, H
      wave at 20% of H-max, M-max and H-reflex latency were recorded in 10 subjects
      (apparently healthy, ages 19-36) before and after exposure to 3 hours of
      NaHCO(3), CaCO(3), NH(4)Cl (all at 0.3 g/kg) or 10 minutes 7% Carbon dioxide
      (CO(2)) administration. NaHCO(3) increased capillary blood pH, CaCO(3) did not
      change capillary blood pH, and NH(4)Cl and 7% CO(2) decreased capillary blood pH.
      H-max and H-wave at 20% of M-max size were significantly decreased with no change
      in M-max, and H-reflex latency significantly increased during 7% CO(2)
      administration only. No other changes in H-maximum size or H-reflex latency in
      response to dry chemical administration were observed. Seven percent CO(2)
      administration reduces the size and increases the latency of the H-maximum size
      as previously found, but other chemicals which alter capillary blood pH do not.
      CO(2) modulates afferent nerve function, and does so, it appears, independent of
      changes in capillary blood pH.

PMID- 24134188
TI  - SNP marker discovery, linkage map construction and identification of QTLs for
      enhanced salinity tolerance in field pea (Pisum sativum L.).
AB  - BACKGROUND: Field pea (Pisum sativum L.) is a self-pollinating, diploid, cool
      season food legume. Crop production is constrained by multiple biotic and abiotic
      stress factors, including salinity, that cause reduced growth and yield. Recent
      advances in genomics have permitted the development of low-cost high-throughput
      genotyping systems, allowing the construction of saturated genetic linkage maps
      for identification of quantitative trait loci (QTLs) associated with traits of
      interest. Genetic markers in close linkage with the relevant genomic regions may
      then be implemented in varietal improvement programs. RESULTS: In this study,
      single nucleotide polymorphism (SNP) markers associated with expressed sequence
      tags (ESTs) were developed and used to generate comprehensive linkage maps for
      field pea. From a set of 36,188 variant nucleotide positions detected through in
      silico analysis, 768 were selected for genotyping of a recombinant inbred line
      (RIL) population. A total of 705 SNPs (91.7%) successfully detected segregating
      polymorphisms. In addition to SNPs, genomic and EST-derived simple sequence
      repeats (SSRs) were assigned to the genetic map in order to obtain an evenly
      distributed genome-wide coverage. Sequences associated with the mapped molecular
      markers were used for comparative genomic analysis with other legume species.
      Higher levels of conserved synteny were observed with the genomes of Medicago
      truncatula Gaertn. and chickpea (Cicer arietinum L.) than with soybean (Glycine
      max [L.] Merr.), Lotus japonicus L. and pigeon pea (Cajanus cajan [L.] Millsp.).
      Parents and RIL progeny were screened at the seedling growth stage for responses
      to salinity stress, imposed by addition of NaCl in the watering solution at a
      concentration of 18 dS m-1. Salinity-induced symptoms showed normal distribution,
      and the severity of the symptoms increased over time. QTLs for salinity tolerance
      were identified on linkage groups Ps III and VII, with flanking SNP markers
      suitable for selection of resistant cultivars. Comparison of sequences
      underpinning these SNP markers to the M. truncatula genome defined genomic
      regions containing candidate genes associated with saline stress tolerance.
      CONCLUSION: The SNP assays and associated genetic linkage maps developed in this
      study permitted identification of salinity tolerance QTLs and candidate genes.
      This constitutes an important set of tools for marker-assisted selection (MAS)
      programs aimed at performance enhancement of field pea cultivars.

PMID- 24134190
TI  - Decreased submandibular adiponectin is involved in the progression of autoimmune
      sialoadenitis in non-obese diabetic mice.
AB  - OBJECTIVE: To investigate a possible role of adiponectin in the pathogenesis of
      autoimmune sialoadenitis in non-obese diabetic (NOD) mouse model of Sjogren's
      syndrome. MATERIALS AND METHODS: Expression of adiponectin and its receptors
      (AdipoR1/2) was detected by PCR, immunoblotting, or immunofluorescence. The level
      of adiponectin was quantified by ELISA. Adiponectin-related signaling molecules
      and pro-inflammatory cytokines were examined by PCR or immunoblotting. Apoptosis
      was evaluated by TUNEL staining, flow cytometry, and caspase 3 activation.
      RESULTS: Adiponectin and AdipoR1/2 mRNA and protein were expressed in
      submandibular glands. Adiponectin immunostaining was widely diffused in the
      cytoplasm of acinar and ductal cells. AdipoR1 was mainly distributed in acinar
      cytoplasm, while AdipoR2 was predominantly located at acinar cell membrane.
      Submandibular adiponectin levels were reduced during the progression of
      autoimmune sialoadenitis in 7-, 14-, and 21-week-old NOD mice, while AdipoR1/2
      levels were unchanged. The levels of phosphorylated adenosine monophosphate
      activated protein kinase, extracellular signal-regulated kinase 1/2, and p38
      mitogen-activated protein kinase were decreased, while interferon (IFN)-gamma and
      glandular apoptosis were temporally increased at all time points. Moreover,
      exogenous adiponectin supplement inhibited, whereas neutralizing endogenous
      adiponectin by its antibody promoted IFN-gamma-induced apoptosis and caspase 3
      activation in cultured submandibular acinar cells. CONCLUSIONS: Adiponectin plays
      a protective role on submandibular cells. Decreased adiponectin might promote
      glandular destruction in autoimmune sialoadenitis.

PMID- 24134191
TI  - Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis.
AB  - Cu/Zn-superoxide dismutase is misfolded in familial and sporadic amyotrophic
      lateral sclerosis, but it is not clear how this triggers endoplasmic reticulum
      (ER) stress or other pathogenic processes. Here, we demonstrate that mutant SOD1
      (mSOD1) is predominantly found in the cytoplasm in neuronal cells. Furthermore,
      we show that mSOD1 inhibits secretory protein transport from the ER to Golgi
      apparatus. ER-Golgi transport is linked to ER stress, Golgi fragmentation and
      axonal transport and we also show that inhibition of ER-Golgi trafficking
      preceded ER stress, Golgi fragmentation, protein aggregation and apoptosis in
      cells expressing mSOD1. Restoration of ER-Golgi transport by over-expression of
      coatomer coat protein II subunit Sar1 protected against inclusion formation and
      apoptosis, thus linking dysfunction in ER-Golgi transport to cellular pathology.
      These findings thus link several cellular events in amyotrophic lateral sclerosis
      into a single mechanism occurring early in mSOD1 expressing cells.

PMID- 24134192
TI  - Easing reintegration: telephone support groups for spouses of returning Iraq and
      Afghanistan service members.
AB  - Spouses of returning Iraq (Operation Iraqi Freedom, OIF) and Afghanistan
      (Operation Enduring Freedom, OEF) military service members report increased
      depression and anxiety post deployment as they work to reintegrate the family and
      service member. Reconnecting the family, renegotiating roles that have shifted,
      reestablishing communication patterns, and dealing with mental health concerns
      are all tasks that spouses must undertake as part of reintegration. We tested
      telephone support groups focusing on helping spouses with these basic
      reintegration tasks. Year-long telephone support groups focused on education,
      skills building (communication skills, problem solving training, cognitive
      behavioral techniques, stress management), and support. Spouse depression and
      anxiety were decreased and perceived social support was increased during the
      course of the study. In subgroup analyses, spouses with husbands whose injuries
      caused care difficulties had a positive response to the intervention. However,
      they were more likely to be depressed, be anxious, and have less social support
      compared to participants who had husbands who had no injury or whose injury did
      not cause care difficulty. Study findings suggest that this well-established,
      high-access intervention can help improve quality of life for military spouses
      who are struggling with reintegration of the service member and family. 

PMID- 24134193
TI  - Temporomandibular signs, symptoms, joint alterations and disease activity in
      juvenile idiopathic arthritis - an observational study.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease that
      frequently affects also the temporomandibular joint (TMJ) and associated
      structures. The main aim of this observational study was to describe
      systematically orofacial clinical signs and subjective symptoms in JIA patients,
      classified according to the International League of Associations for Rheumatology
      (ILAR) criteria, and to relate the findings to disease activity and radiological
      TMJ condyle lesions. METHODS: The study was a retrospective evaluation of dental
      and medical records in consecutive JIA patients referred to one of three dental
      specialist clinics in Sweden during an eight-year period. Data concerning
      temporomandibular signs, symptoms and general disease activity were collected and
      condylar alterations were judged on panoramic radiographs. RESULTS: All ILAR
      categories of JIA were represented among the 266 referrals included in the study.
      The distribution of patients among categories resembled the pattern seen in
      epidemiological studies. Persistent oligoarthritis was the largest category with
      36.5% of the patients. Temporomandibular clinical signs (mild, moderate or
      severe) occurred in 57.7% to 92.0%, and subjective symptoms (mild or severe) in
      32.0% to 76.0% of the patients in all categories. Patients in the juvenile
      psoriatic arthritis category had the largest number of orofacial signs and
      symptoms, and patients in the persistent oligoarthritis category had the fewest
      signs and symptoms. There were significant associations between clinical signs as
      well as subjective symptoms and overall disease activity. Half of all the
      patients had undergone panoramic examinations and 37.9% of those were judged to
      have condylar alterations after a mean of 2.9 years after onset. No associations
      between radiological findings and variables, such as signs, symptoms or disease
      activity, were found. CONCLUSIONS: Temporomandibular signs and symptoms can be
      expected to a varying degree, including severe cases, in all JIA categories.
      Clinical and subjective orofacial involvement appears to be related to disease
      activity but not to condylar lesions.

PMID- 24134194
TI  - Nutraceutical intervention improves older adults' cognitive functioning.
AB  - Interventions to improve the cognitive health of older adults are of critical
      importance. In the current study, we conducted a double-blind, placebo-controlled
      clinical trial using a pill-based nutraceutical (NT-020) that contained a
      proprietary formulation of blueberry, carnosine, green tea, vitamin D3, and
      Biovin to evaluate the impact on changes in multiple domains of cognitive
      functioning. One hundred and five cognitively intact adults aged 65-85 years of
      age (M=73.6 years) were randomized to receive NT-020 (n=52) or a placebo (n=53).
      Participants were tested with a battery of cognitive performance tests that were
      classified into six broad domains--episodic memory, processing speed, verbal
      ability, working memory, executive functioning, and complex speed at baseline and
      2 months later. The results indicated that persons taking NT-020 improved
      significantly on two measures of processing speed across the 2-month test period
      in contrast to persons on the placebo whose performance did not change. None of
      the other cognitive ability measures were related to intervention group. The
      results also indicated that the NT-020 was well tolerated by older adults, and
      the presence of adverse events or symptoms did not differ between the NT-020 and
      placebo groups. Overall, the results of the current study were promising and
      suggest the potential for interventions like these to improve the cognitive
      health of older adults.

PMID- 24134195
TI  - The gut microbiota and the liver: implications for clinical practice.
AB  - While a central role for the microbiota in the precipitation of infectious and
      non-infectious complications of liver disease has been long established, evidence
      for a more fundamental role in the etiology of several liver diseases continues
      to accumulate. However, though progress is rapidly occurring in this area, the
      definitive delineation of the precise relevance of changes in the microbiota to
      various forms and stages of liver disease is still far from complete. While high
      quality clinical evidence supports the use of antibiotic therapy, in the
      management of hepatic encephalopathy, spontaneous bacterial peritonitis and other
      infectious complications, how these interventions impact on the microbiota and
      microbiota-host interactions has not been clearly defined. Although probiotics
      and even, perhaps, fecal transplantation hold promise in the management of liver
      disease, and the potential impact of probiotics is supported by a considerable
      amount of laboratory data, high-quality clinical evidence is scanty. 

PMID- 24134196
TI  - Understanding the self-assembly of proteins onto gold nanoparticles and quantum
      dots driven by metal-histidine coordination.
AB  - Coupling of polyhistidine-appended biomolecules to inorganic nanocrystals driven
      by metal-affinity interactions is a greatly promising strategy to form hybrid
      bioconjugates. It is simple to implement and can take advantage of the fact that
      polyhistidine-appended proteins and peptides are routinely prepared using well
      established molecular engineering techniques. A few groups have shown its
      effectiveness for coupling proteins onto Zn- or Cd-rich semiconductor quantum
      dots (QDs). Expanding this conjugation scheme to other metal-rich nanoparticles
      (NPs) such as AuNPs would be of great interest to researchers actively seeking
      effective means for interfacing nanostructured materials with biology. In this
      report, we investigated the metal-affinity driven self-assembly between AuNPs and
      two engineered proteins, a His7-appended maltose binding protein (MBP-His) and a
      fluorescent His6-terminated mCherry protein. In particular, we investigated the
      influence of the capping ligand affinity to the nanoparticle surface, its
      density, and its lateral extension on the AuNP-protein self-assembly. Affinity
      gel chromatography was used to test the AuNP-MPB-His7 self-assembly, while NP-to
      mCherry-His6 binding was evaluated using fluorescence measurements. We also
      assessed the kinetics of the self-assembly between AuNPs and proteins in
      solution, using time-dependent changes in the energy transfer quenching of
      mCherry fluorescent proteins as they immobilize onto the AuNP surface. This
      allowed determination of the dissociation rate constant, Kd(-1) ~ 1-5 nM.
      Furthermore, a close comparison of the protein self-assembly onto AuNPs or QDs
      provided additional insights into which parameters control the interactions
      between imidazoles and metal ions in these systems. 

PMID- 24134198
TI  - Bullous scabies failing to respond to glucocorticoids, immunoglobulin, and
      cyclophosphamide.

PMID- 24134199
TI  - Staging, prognostic factors and adjuvant therapy of intrahepatic
      cholangiocarcinoma after curative resection.
AB  - BACKGROUND & AIMS: Prognostic factors and adjuvant therapy of intrahepatic
      cholangiocarcinoma (ICC) after curative resection were not clear. We aim to
      analyse prognostic factors after curative resection and evaluate adjuvant therapy
      and survival based on the new staging system. METHODS: A retrospective analysis
      of 283 patients who underwent surgical exploration for ICC was performed. Staging
      was performed according to the 7th edition AJCC staging manual. Univariate and
      multivariate analyses were used to evaluate independent prognostic factors.
      RESULTS: The difference for OS at different TNM stages after R0 resection was
      significant (P < 0.001). Despite regional lymph node metastasis, tumour number
      and vascular invasion, serum GGT level was also an independent prognostic factor
      for OS of patients after R0 resection. The incidence of biliary and vascular
      invasion was significantly higher in high GGT group than in normal GGT group.
      Factors predictive of recurrence were multiple tumours and regional lymph node
      metastasis. After R0 resection, adjuvant TACE not only did not improve the OS of
      patients at TNM stage I (P = 0.508), but significantly promoted recurrence of
      these patients (P = 0.006). Only patients at TNM stage II, III and IV benefited
      from adjuvant TACE for longer survival, while the recurrence rates were not
      affected. CONCLUSIONS: The new staging system can predict the survival of ICC
      patients after R0 resection. High GGT level may be suggestive of biliary and
      vascular invasion and was an independent risk factor for OS after R0 resection.
      Adjuvant TACE may be indicated only for patients at advanced stages for better
      survival.

PMID- 24134200
TI  - Different trajectories of adolescent alcohol use: testing gene-environment
      interactions.
AB  - BACKGROUND: Transitions into heavy alcohol use often already take place during
      adolescence and are likely to be both genetically and environmentally determined.
      Therefore, in a 6-wave longitudinal study, we examined the effects of DRD2 Taq1A
      and OPRM1 A118G genotypes and the interaction with parental rule-setting on
      different groups of adolescent drinkers. METHODS: Growth mixture modeling
      resulted in 3 distinct groups of adolescent drinkers: light drinkers (n = 346),
      moderate drinkers (n = 178), and heavy drinkers (n = 72). RESULTS: Multinomial
      regression showed that moderate drinkers carried the OPRM1 G allele and received
      lower levels of parental rule-setting significantly more often than the light
      drinking group. No other significant main effects of DRD2, OPRM1, and rule
      setting were found. The interaction between OPRM1 genotype and parental rule
      setting significantly distinguished the heavy drinkers from the light (p < 0.001)
      and moderate groups (p = 0.055): Particularly, the alcohol use of OPRM1 G allele
      carriers was affected by parental rule-setting, while AA genotype carriers
      remained largely unaffected by parental rules. CONCLUSIONS: Findings showed that
      different trajectories of adolescent drinking are preceded by a gene-parenting
      interaction. These results concur with Belsky's theory of plasticity (2009), as
      well as with Shanahan and Hofer's typology of a controlling and restricting gene
      environment interaction (2005).

PMID- 24134201
TI  - Convergent structure of multitrophic communities over three continents.
AB  - Ecological theory predicts that communities using the same resources should have
      similar structure, but evolutionary constraints on colonisation and niche shifts
      may hamper such convergence. Multitrophic communities of wasps exploiting fig
      fruits, which first evolved about 75MYA, do not show long-term 'inheritance' of
      taxonomic (lineage) composition or species diversity. However, communities on
      three continents have converged ecologically in the presence and relative
      abundance of five insect guilds that we define. Some taxa fill the same niches in
      each community (phylogenetic niche conservatism). However, we show that overall
      convergence in ecological community structure depends also on a combination of
      niche shifts by resident lineages and local colonisations of figs by other insect
      lineages. Our study explores new ground, and develops new heuristic tools, in
      combining ecology and phylogeny to address patterns in the complex multitrophic
      communities of insect on plants, which comprise a large part of terrestrial
      biodiversity. 

PMID- 24134202
TI  - Development of a wound healing index for patients with chronic wounds.
AB  - Randomized controlled trials in wound care generalize poorly because they exclude
      patients with significant comorbid conditions. Research using real-world wound
      care patients is hindered by lack of validated methods to stratify patients
      according to severity of underlying illnesses. We developed a comprehensive
      stratification system for patients with wounds that predicts healing likelihood.
      Complete medical record data on 50,967 wounds from the United States Wound
      Registry were assigned a clear outcome (healed, amputated, etc.). Factors known
      to be associated with healing were evaluated using logistic regression models.
      Significant variables (p < 0.05) were determined and subsequently tested on a
      holdout sample of data. A different model predicted healing for each wound type.
      Some variables predicted significantly in nearly all models: wound size, wound
      age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade
      or stage), being nonambulatory, and requiring hospitalization during the course
      of care. Variables significant in some models included renal failure, renal
      transplant, malnutrition, autoimmune disease, and cardiovascular disease. All
      models validated well when applied to the holdout sample. The "Wound Healing
      Index" can validly predict likelihood of wound healing among real-world patients
      and can facilitate comparative effectiveness research to identify patients
      needing advanced therapeutics.

PMID- 24134203
TI  - Structural and functional characterisation of the methionine adenosyltransferase
      from Thermococcus kodakarensis.
AB  - BACKGROUND: Methionine adenosyltransferases catalyse the synthesis of S
      adenosylmethionine, a cofactor abundant in all domains of life. In contrast to
      the enzymes from bacteria and eukarya that show high sequence similarity,
      methionine adenosyltransferases from archaea diverge on the amino acid sequence
      level and only few conserved residues are retained. RESULTS: We describe the
      initial characterisation and the crystal structure of the methionine
      adenosyltransferase from the hyperthermophilic archaeon Thermococcus
      kodakarensis. As described for other archaeal methionine adenosyltransferases the
      enzyme is a dimer in solution and shows high temperature stability. The overall
      structure is very similar to that of the bacterial and eukaryotic enzymes
      described, with some additional features that might add to the stability of the
      enzyme. Compared to bacterial and eukaryotic structures, the active site
      architecture is largely conserved, with some variation in the substrate/product
      binding residues. A flexible loop that was not fully ordered in previous
      structures without ligands in the active side is clearly visible and forms a
      helix that leaves an entrance to the active site open. CONCLUSIONS: The similar
      three-dimensional structures of archaeal and bacterial or eukaryotic methionine
      adenosyltransferases support that these enzymes share an early common ancestor
      from which they evolved independently, explaining the low similarity in their
      amino acid sequences. Furthermore, methionine adenosyltransferase from T.
      kodakarensis is the first structure without any ligands bound in the active site
      where the flexible loop covering the entrance to the active site is fully
      ordered, supporting a mechanism postulated earlier for the methionine
      adenosyltransferase from E. coli. The structure will serve as a starting point
      for further mechanistic studies and permit the generation of enzyme variants with
      different characteristics by rational design.

PMID- 24134204
TI  - A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of
      GSK3beta to phosphorylate cyclin D1 at Thr(286), not Thr(288).
AB  - DYRK1B (dual-specificity tyrosine phosphorylation-regulated kinase 1B) is
      amplified in certain cancers and may be an oncogene; however, our knowledge of
      DYRK1B has been limited by the lack of selective inhibitors. In the present study
      we describe AZ191, a potent small molecule inhibitor that selectively inhibits
      DYRK1B in vitro and in cells. CCND1 (cyclin D1), a key regulator of the mammalian
      G1-S-phase transition, is phosphorylated on Thr(286) by GSK3beta (glycogen
      synthase kinase 3beta) to promote its degradation. DYRK1B has also been proposed
      to promote CCND1 turnover, but was reported to phosphorylate Thr(288) rather than
      Thr(286). Using in vitro kinase assays, phospho-specific immunoblot analysis and
      MS in conjunction with AZ191 we now show that DYRK1B phosphorylates CCND1 at
      Thr(286), not Thr(288), in vitro and in cells. In HEK (human embryonic kidney)
      293 and PANC-1 cells (which exhibit DYRK1B amplification) DYRK1B drives Thr(286)
      phosphorylation and proteasome-dependent turnover of CCND1 and this is abolished
      by AZ191 or DYRK1B RNAi, but not by GSK3beta inhibitors or GSK3beta RNAi. DYRK1B
      expression causes a G1-phase cell-cycle arrest, but overexpression of CCND1 (wild
      type or T286A) fails to overcome this; indeed, DYRK1B also promotes the
      expression of p21CIP1 (21 kDa CDK-interacting protein 1) and p27KIP1 (CDK
      inhibitory protein 1). The results of the present study demonstrate for the first
      time that DYRK1B is a novel Thr(286)-CCND1 kinase that acts independently of
      GSK3beta to promote CCND1 degradation. Furthermore, we anticipate that AZ191 may
      prove useful in defining further substrates and biological functions of DYRK1B.

PMID- 24134205
TI  - Racial and ethnic differences in risk factors associated with suicidal behavior
      among young adults in the USA.
AB  - OBJECTIVE: The objectives of this study are to examine racial and ethnic
      differences in suicidal behaviour, its main risk factors, and the effect of the
      risk factors on suicidal behaviour in young adults in the United States. DESIGN:
      Using nationally representative data (n=10,585) from Add Health, we calculate the
      prevalence of suicidal behavior and associated risk factors for non-Hispanic
      White, non-Hispanic Black, and Hispanic youth (aged 18-26) using logistic
      regression models of suicidal ideation stratified by race. RESULTS: Non-Hispanic
      White and Hispanic young adults have higher rates of suicidal ideation than their
      non-Hispanic Black counterparts, but racial/ethnic differences in attempts are
      not statistically significant. Non-Hispanic Whites and Hispanic young adults are
      more likely to possess key risk factors for suicide. With the exception of
      substance use variables (i.e. alcohol and marijuana use) which appear to be more
      conducive to suicidal ideation in non-Hispanic Black than in non-Hispanic White
      young adults, the effects of risk factors appear to be similar across
      race/ethnicity. CONCLUSION: The higher prevalence of suicidal ideation in non
      Hispanic White and Hispanic young adults may be driven by their greater exposure
      to risk factors, as opposed to differences in the effects of these risk factors.
      More research is needed to uncover why non-Hispanic White and Hispanic young
      adults have higher rates of suicidal ideation than their non-Hispanic Black
      counterparts; yet, rates of suicide attempts are comparable and non-Hispanic
      White young adults have the highest rate of completed suicides.

PMID- 24134206
TI  - Stage migration of renal cell carcinoma at a single Japanese university hospital:
      24-year study.

PMID- 24134207
TI  - Elevated levels of CXCL10 in the Periodic Fever, Aphthous stomatitis, Pharyngitis
      and cervical Adenitis syndrome (PFAPA) during and between febrile episodes; an
      indication of a persistent activation of the innate immune system.
AB  - BACKGROUND: The Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical
      Adenitis syndrome (PFAPA) is the most common periodic fever syndrome in
      childhood. Clinically, PFAPA may resemble autoinflammatory diseases, but the
      etiology is not fully understood. METHODS: We measured inflammatory proteins in
      plasma and hematologic parameters in children with PFAPA during and between
      febrile episodes, and in a control group with suspected bacterial pneumonia. In
      children with PFAPA, a first blood sample was taken within 24 hours of a febrile
      episode and a second sample between episodes. In children with pneumonia, the
      first sample was taken shortly after admission and a second sample after full
      recovery. RESULTS: A total of 22 children with PFAPA and 14 children with
      pneumonia were included. In children with PFAPA, levels of interleukin (IL) 6,
      CXCL10 and CCL4 were significantly increased during febrile episodes. The levels
      of IL-6 and CXCL10 were higher in children with PFAPA during febrile episodes
      than in children with pneumonia. The levels of CXCL10 remained higher in children
      with PFAPA between febrile episodes compared to children with pneumonia after
      recovery. Children with PFAPA had a relative eosinopenia and lymphocytopenia with
      reduced numbers of both CD4+ and CD8+ T cells during febrile episodes. This
      pattern was not observed in the children with pneumonia. CONCLUSIONS: The results
      indicate an innate immune response as the initial step in PFAPA, and a subsequent
      adaptive response with activation and redistribution of T cells. Moreover, an
      activation of the innate immune system involving CXCL10 may persist between
      febrile episodes. CXCL10 may be a possibly clinical marker in children with
      PFAPA.

PMID- 24134208
TI  - New 7-methylguanine derivatives targeting the influenza polymerase PB2 cap
      binding domain.
AB  - The heterotrimeric influenza virus polymerase performs replication and
      transcription of viral RNA in the nucleus of infected cells. Transcription by
      "cap-snatching" requires that host-cell pre-mRNAs are bound via their 5' cap to
      the PB2 subunit. Thus, the PB2 cap-binding site is potentially a good target for
      new antiviral drugs that will directly inhibit viral replication. Docking studies
      using the structure of the PB2 cap-binding domain suggested that 7-alkylguanine
      derivatives substituted at position N-9 and N-2 could be good candidates. Four
      series of 7,9-di- and 2,7,9-trialkyl guanine derivatives were synthesized and
      evaluated by an AlphaScreen assay in competition with a biotinylated cap
      analogue. Three synthesized compounds display potent in vitro activity with IC50
      values lower than 10 MUM. High-resolution X-ray structures of three inhibitors in
      complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and
      provide detailed information for further compound optimization. 

PMID- 24134209
TI  - An Implication of Health Sector Reform for Disadvantaged Women's Struggle for
      Birth Control: A Case of Kurdish Rural-Urban Migrant Women in Van, Turkey.
AB  - In this article, we examine how socioeconomically disadvantaged women are
      affected by health sector reform and family planning policy changes in Turkey
      through a case study of Kurdish women's struggles for birth control. In Turkey, a
      family planning program became relatively marginalized in primary health care
      services as a result of health sector reform as well as a shift of population
      policy toward a moderately pronatal approach. We argue that an emerging health
      care system would leave disadvantaged women unable to benefit from contraceptives
      and would perpetuate reproductive health inequalities between women in the
      country. 

PMID- 24134210
TI  - Cutaneous porphyrias part II: treatment strategies.
AB  - The porphyrias are diverse in pathophysiology, clinical presentation, severity,
      and prognosis, presenting a diagnostic and therapeutic challenge. Although not
      easily curable, the dermatological manifestations of these diseases,
      photosensitivity and associated cutaneous pathology, can be effectively prevented
      and managed. Sun avoidance is essential, and patient education regarding the
      irreversibility of photocutaneous damage is a necessary corollary. Beyond
      preventative measures, the care of fragile, vulnerable skin, and pain management,
      each of the porphyrias has a limited number of unique additional therapeutic
      options. Many of the treatments have been published only in small case series or
      anecdotal reports and do not have well-understood nor proven mechanisms of
      action. This article presents a comprehensive review of available therapeutic
      options and long-term management recommendations for the cutaneous porphyrias. 

PMID- 24134211
TI  - Outcomes of preterm infants receiving positive pressure support at term corrected
      gestation.
AB  - AIM: To establish the mortality rate to hospital discharge of very preterm
      infants who remain on positive pressure support (PPS) at term corrected gestation
      and describe factors that are associated with increased mortality. METHODS:
      Infants born <30 weeks' gestation between 1 January 2001 and 31 December 2009 who
      were receiving PPS at 40 weeks' postmenstrual age (PMA) were identified from our
      database, and their medical records reviewed. The fraction of inspired oxygen
      (FiO2 ), mean airway pressure and partial pressure of carbon dioxide (PaCO2 ) at
      40 weeks' PMA were recorded. Receiver operating characteristic curves for
      mortality before discharge were generated. RESULTS: One thousand three hundred
      fifty-nine of 1572 infants survived to term. Forty-nine infants were receiving
      PPS at 40 weeks' PMA. Of these, 15 (31%) infants died before hospital discharge.
      All three infants who were ventilated via an endotracheal tube died. Increased
      oxygen requirement at term was associated with increased risk of death before
      discharge (area under curve (AUC) 0.75). FiO2 > 0.5 was associated with an 80%
      risk of death. PaCO2 was not predictive of death (AUC 0.49). CONCLUSIONS: Two
      thirds of very preterm infants who remained on PPS at 40 weeks' PMA survived to
      hospital discharge. Risk of death rises with increasing oxygen requirements. All
      five infants with FiO2 > 0.70 died.

PMID- 24134212
TI  - Simultaneous dual protein labeling using a triorthogonal reagent.
AB  - Construction of heterofunctional proteins is a rapidly emerging area of
      biotherapeutics. Combining a protein with other moieties, such as a targeting
      element, a toxic protein or small molecule, and a fluorophore or polyethylene
      glycol (PEG) group, can improve the specificity, functionality, potency, and
      pharmacokinetic profile of a protein. Protein farnesyl transferase (PFTase) is
      able to site-specifically and quantitatively prenylate proteins containing a C
      terminal CaaX-box amino acid sequence with various modified isoprenoids. Here, we
      describe the design, synthesis, and application of a triorthogonal reagent, 1,
      that can be used to site-specifically incorporate an alkyne and aldehyde group
      simultaneously into a protein. To illustrate the capabilities of this approach, a
      protein was enzymatically modified with compound 1 followed by oxime ligation and
      click reaction to simultaneously incorporate an azido-tetramethylrhodamine
      (TAMRA) fluorophore and an aminooxy-PEG moiety. This was performed with both a
      model protein [green fluorescent protein (GFP)] as well as a therapeutically
      useful protein [ciliary neurotrophic factor (CNTF)]. Next, a protein was
      enzymatically modified with compound 1 followed by coupling to an azido-bis
      methotrexate dimerizer and aminooxy-TAMRA. Incubation of that construct with a
      dihydrofolate reductase (DHFR)-DHFR-anti-CD3 fusion protein resulted in the self
      assembly of nanoring structures that were endocytosed into T-leukemia cells and
      visualized therein. These results highlight how complex multifunctional protein
      assemblies can be prepared using this facile triorthogonal approach. 

PMID- 24134213
TI  - Androgen supplementation during aging: development of a physiologically
      appropriate protocol.
AB  - Men show an age-related decline in the circulating levels of testosterone (T) and
      dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in
      developing androgen supplementation paradigms for old men that replicate the
      hormone profiles of young adults. In the present study, we used old (21-26 years
      old) male rhesus monkeys as a model to examine the efficacy of an androgen
      supplementation paradigm that comprised oral T administration (12 mg/kg body
      weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA
      administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame
      oil/chocolate) in the morning. After 5 days of repeated hormone supplementation,
      serial blood samples were remotely collected from each animal hourly across the
      24-hr day, and assayed for cortisol, DHEAS, T, 5alpha-dihydrotestosterone (DHT),
      estrone (E1), and 17beta-estradiol (E2). Following androgen supplementation, T
      levels were significantly elevated and this was associated with a more sustained
      nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2.
      Plasma DHEAS levels were also significantly elevated after androgen
      supplementation; DHEAS levels rose in the early morning and gradually declined
      during the course of the day, closely mimicking the profiles observed in young
      adults (7-12 years old); in contrast, cortisol levels were unaltered by the
      supplementation. Together the data demonstrate a non-invasive androgen
      supplementation paradigm that restores youthful circulating androgen levels in
      old male primates. Because this paradigm preserves the natural circulating
      circadian hormone patterns, we predict that it will produce fewer adverse side
      effects, such as perturbed sleep or cognitive impairment.

PMID- 24134214
TI  - Characteristics of patients complaining of halitosis and factors associated with
      halitosis.
AB  - OBJECTIVES: To describe the characteristics of patients who visited halitosis
      clinic and to investigate the factors that may associate with halitosis.
      MATERIALS AND METHODS: Nine hundred and eleven patients, who visited halitosis
      clinic for consultations, underwent organoleptic tests and volatile sulfur
      compound (VSC) measurements with a portable sulfide monitor. The oral health of
      patients, including dental caries, oral hygiene, and gingival inflammation
      status, was assessed. Questionnaires were used to obtain information on
      demographics, oral hygiene practices, and dietary habits. RESULTS: Of the 911
      patients, more females than males visited the clinic. Patients' age ranged from
      18 to 82 years (mean +/- s.d.: 40.8 +/- 14.1). Almost 30% of patients had
      complained of halitosis for over 5 years before looking into treatments.
      Approximately half of the patients self-perceived that they were unable to get
      close to others. Around 77% of patients had halitosis. Results of multiple
      logistic regressions for organoleptic scores and VSC values showed that tongue
      coating and tongue scraping were significantly associated with halitosis (P <
      0.05). CONCLUSIONS: Among these Chinese patients, over three-quarters of patients
      had halitosis, and negative impacts on social communications were observed.
      Tongue coating was the most important factor responsible for halitosis.

PMID- 24134215
TI  - Bi(1)-(x)Sb(x) alloy nanocrystals: colloidal synthesis, charge transport, and
      thermoelectric properties.
AB  - Nanostructured Bi1-xSbx alloys constitute a convenient system to study charge
      transport in a nanostructured narrow-gap semiconductor with promising
      thermoelectric properties. In this work, we developed the colloidal synthesis of
      monodisperse sub-10 nm Bi1-xSbx alloy nanocrystals (NCs) with controllable size
      and compositions. The surface chemistry of Bi1-xSbx NCs was tailored with
      inorganic ligands to improve the interparticle charge transport as well as to
      control the carrier concentration. Temperature-dependent (10-300 K) electrical
      measurements were performed on the Bi1-xSbx NC based pellets to investigate the
      effect of surface chemistry and grain size (~10-40 nm) on their charge transport
      properties. The Hall effect measurements revealed that the temperature dependence
      of carrier mobility and concentration strongly depended on the grain size and the
      surface chemistry, which was different from the reported bulk behavior. At low
      temperatures, electron mobility in nanostructured Bi1-xSbx was directly
      proportional to the average grain size, while the concentration of free carriers
      was inversely proportional to the grain size. We propose a model explaining such
      behavior. Preliminary measurements of thermoelectric properties showed a ZT value
      comparable to those of bulk Bi1-xSbx alloys at 300 K, suggesting a potential of
      Bi1-xSbx NCs for low-temperature thermoelectric applications. 

PMID- 24134216
TI  - Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult
      volunteers with mild or moderate hepatic impairment.
AB  - AIMS: To evaluate the pharmacokinetics and pharmacodynamics after a single dose
      of liposomal mifamurtide (liposomal muramyl tripeptide phospatidyl ethanolamine;
      MEPACT((r))) in adult subjects with mild (Child-Pugh Class A) or moderate (Child
      Pugh Class B) hepatic impairment in comparison with age-, weight- and sex-matched
      healthy subjects with normal hepatic function. METHODS: Subjects received a 4 mg
      dose of liposomal mifamurtide via 1 h intravenous infusion. Blood samples were
      collected over 72 h for pharmacokinetic and pharmacodynamic assessments (changes
      in serum interleukin-6, tumour necrosis factor-alpha and C-reactive protein).
      RESULTS: Thirty-seven subjects were enrolled: nine with mild hepatic impairment,
      eight with moderate hepatic impairment and 20 matched healthy subjects. Geometric
      least-square mean ratios of total mifamurtide AUCinf for the mild hepatic
      impairment and moderate hepatic impairment groups vs. matched healthy subjects
      were 105% (90% confidence interval, 83.6-132%) and 119% (90% confidence interval,
      94.1-151%), respectively, which are below the protocol-specified threshold (150%)
      to require development of dose-modification recommendations. Pharmacodynamic
      parameters for changes in serum interleukin-6 and tumour necrosis factor-alpha
      concentrations were generally similar across hepatic function groups. Mifamurtide
      induced increases in serum C-reactive protein were attenuated in the moderate
      hepatic impairment group, consistent with the liver being the major organ of C
      reactive protein synthesis. No grade >=3 adverse events were seen in subjects
      administered mifamurtide (4 mg). CONCLUSIONS: These results support the
      conclusion that mild or moderate hepatic impairment does not produce clinically
      meaningful effects on the clinical pharmacokinetics or pharmacodynamics of
      mifamurtide; no dose modifications are needed in these special patient
      populations based on clinical pharmacological considerations.

PMID- 24134217
TI  - Reflecting on the iridophore transcriptome, and more.

PMID- 24134219
TI  - Risks of neurological and immune-related diseases, including narcolepsy, after
      vaccination with Pandemrix: a population- and registry-based cohort study with
      over 2 years of follow-up.
AB  - OBJECTIVES: To investigate the association between vaccination with Pandemrix and
      risk of selected neurological and immune-related diseases including narcolepsy.
      DESIGN: Population-based prospective cohort study using data from regional
      vaccination registries and national health registries. SETTING: Seven healthcare
      regions in Sweden comprising 61% of the Swedish population. SUBJECTS: Study
      population of 3,347,467 vaccinated and 2,497,572 nonvaccinated individuals
      (vaccination coverage ~ 60%) followed between 2009 and 2011 for 6.9 million
      person-years after exposure and 6.0 million person-years without exposure. MAIN
      OUTCOME MEASURE AND ANALYSIS: First recorded diagnosis of neurological and immune
      related diseases. Relative risks [hazard ratios (HRs) with 95% confidence
      intervals (CIs)] assessed using Cox regression, adjusted for covariates. RESULTS:
      For all selected neurological and immune-related outcomes under study, other than
      allergic vaccine reactions (for which we verified an expected increase in risk)
      and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three
      fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79;
      that is, four additional cases per 100,000 person-years) in individuals <= 20
      years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75)
      amongst young adults between 21 and 30 years of age. The excess risk declined
      successively with increasing age at vaccination; no increase in risk was seen
      after 40 years of age. CONCLUSIONS: For a large number of selected neurological
      and immune-related diseases, we could neither confirm any causal association with
      Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk
      for a diagnosis of narcolepsy in individuals <= 20 years of age and observed a
      trend towards an increased risk also amongst young adults between 21 and 30
      years.

PMID- 24134218
TI  - Hyperammonaemia induces hepatic injury with alteration of gene expression
      profiles.
AB  - BACKGROUND: Hyperammonaemia is a serious metabolic disorder commonly observed in
      patients with hepatic failure. However, it is unknown whether hyperammonaemia has
      a direct adverse effect on the hepatocytes and thereby serves as both a cause and
      effect of hepatic failure. AIMS: The purposes were to determine whether hepatic
      injury can be caused by hyperammonaemia, and if so, screen the key genes involved
      in hyperammonaemia. METHODS: Hyperammonaemic rats were established via
      intragastric administration of the ammonium chloride solution. The liver tissues
      were assessed via biochemistry, histology, immunohistochemistry and microarray
      analysis. Selected genes were confirmed by quantitative RT-PCR. RESULTS:
      Administration of the ammonium chloride caused the hyperammonaemia, accompanied
      with the changes of plasma markers indicating hepatic injury. A pathological
      assessment demonstrated increased apoptosis and higher level of cyclin D1 and
      cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver
      samples and 198 differentially expressed genes were identified in hyperammonaemic
      rats and validated by quantitative RT-PCR. These genes were associated with many
      vital functional classes and belonged to different signal transduction pathways.
      CONCLUSIONS: This study demonstrates that hyperammonaemia can directly induce
      hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide
      the possible explanations and mechanisms for the hepatic injury induced by
      hyperammonaemia.

PMID- 24134220
TI  - Depressive symptoms, relational turbulence, and the reintegration difficulty of
      military couples following wartime deployment.
AB  - During reunion following wartime deployment, military couples are at risk for
      both depression and relationship distress (Bowling & Sherman, 2008). This article
      applies the relational turbulence model ( Knobloch & Theiss, 2011a ; Solomon &
      Theiss, 2011 ) to understand the difficulty military couples may experience upon
      homecoming. One hundred and eighteen military couples completed an online
      questionnaire once per month for the first 3 months upon reunion following
      wartime deployment. Multilevel modeling results indicated that people's
      depressive symptoms (H1), relational uncertainty (H2), and interference from
      partners (H3) predicted their difficulty with reintegration. A few partner
      effects were apparent as well. These findings illuminate the dynamics of the
      reunion period, extend the relational turbulence model, and suggest guidelines
      for helping military couples preserve well-being during reintegration following
      wartime deployment. 

PMID- 24134221
TI  - Use of principal components analysis and protein microarray to explore the
      association of HIV-1-specific IgG responses with disease progression.
AB  - The role of HIV-1-specific antibody responses in HIV disease progression is
      complex and would benefit from analysis techniques that examine clusterings of
      responses. Protein microarray platforms facilitate the simultaneous evaluation of
      numerous protein-specific antibody responses, though excessive data are
      cumbersome in analyses. Principal components analysis (PCA) reduces data
      dimensionality by generating fewer composite variables that maximally account for
      variance in a dataset. To identify clusters of antibody responses involved in
      disease control, we investigated the association of HIV-1-specific antibody
      responses by protein microarray, and assessed their association with disease
      progression using PCA in a nested cohort design. Associations observed among
      collections of antibody responses paralleled protein-specific responses. At
      baseline, greater antibody responses to the transmembrane glycoprotein (TM) and
      reverse transcriptase (RT) were associated with higher viral loads, while
      responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and
      integrase (IN) proteins were associated with lower viral loads. Over 12 months
      greater antibody responses were associated with smaller decreases in CD4 count
      (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and
      protein microarray analyses highlighted a collection of HIV-specific antibody
      responses that together were associated with reduced disease progression, and may
      not have been identified by examining individual antibody responses. This
      technique may be useful to explore multifaceted host-disease interactions, such
      as HIV coinfections.

PMID- 24134222
TI  - Combined linkage and association mapping reveals candidates for Scmv1, a major
      locus involved in resistance to sugarcane mosaic virus (SCMV) in maize.
AB  - BACKGROUND: Sugarcane mosaic virus (SCMV) disease causes substantial losses of
      grain yield and forage biomass in susceptible maize cultivars. Maize resistance
      to SCMV is associated with two dominant genes, Scmv1 and Scmv2, which are located
      on the short arm of chromosome 6 and near the centromere region of chromosome 3,
      respectively. We combined both linkage and association mapping to identify
      positional candidate genes for Scmv1. RESULTS: Scmv1 was fine-mapped in a
      segregating population derived from near-isogenic lines and further validated and
      fine-mapped using two recombinant inbred line populations. The combined results
      assigned the Scmv1 locus to a 59.21-kb interval, and candidate genes within this
      region were predicted based on the publicly available B73 sequence. None of three
      predicted genes that are possibly involved in the disease resistance response are
      similar to receptor-like resistance genes. Candidate gene-based association
      mapping was conducted using a panel of 94 inbred lines with variable resistance
      to SCMV. A presence/absence variation (PAV) in the Scmv1 region and two
      polymorphic sites around the Zmtrx-h gene were significantly associated with SCMV
      resistance. CONCLUSION: Combined linkage and association mapping pinpoints Zmtrx
      h as the most likely positional candidate gene for Scmv1. These results pave the
      way towards cloning of Scmv1 and facilitate marker-assisted selection for
      potyvirus resistance in maize.

PMID- 24134223
TI  - Structural and biochemical characterization of the essential DsbA-like disulfide
      bond forming protein from Mycobacterium tuberculosis.
AB  - BACKGROUND: Bacterial Disulfide bond forming (Dsb) proteins facilitate proper
      folding and disulfide bond formation of periplasmic and secreted proteins.
      Previously, we have shown that Mycobacterium tuberculosis Mt-DsbE and Mt-DsbF aid
      in vitro oxidative folding of proteins. The M. tuberculosis proteome contains
      another predicted membrane-tethered Dsb protein, Mt-DsbA, which is encoded by an
      essential gene. RESULTS: Herein, we present structural and biochemical analyses
      of Mt-DsbA. The X-ray crystal structure of Mt-DsbA reveals a two-domain
      structure, comprising a canonical thioredoxin domain with the conserved CXXC
      active site cysteines in their reduced form, and an inserted alpha-helical domain
      containing a structural disulfide bond. The overall fold of Mt-DsbA resembles
      that of other DsbA-like proteins and not Mt-DsbE or Mt-DsbF. Biochemical
      characterization demonstrates that, unlike Mt-DsbE and Mt-DsbF, Mt-DsbA is unable
      to oxidatively fold reduced, denatured hirudin. Moreover, on the substrates
      tested in this study, Mt-DsbA has disulfide bond isomerase activity contrary to
      Mt-DsbE and Mt-DsbF. CONCLUSION: These results suggest that Mt-DsbA acts upon a
      distinct subset of substrates as compared to Mt-DsbE and Mt-DsbF. One could
      speculate that Mt-DsbE and Mt-DsbF are functionally redundant whereas Mt-DsbA is
      not, offering an explanation for the essentiality of Mt-DsbA in M. tuberculosis.

PMID- 24134224
TI  - Hyperbaric oxygen treatment reduces neutrophil-endothelial adhesion in chronic
      wound conditions through S-nitrosation.
AB  - Hyperbaric oxygen (HBO) therapy is an effective treatment for diabetic chronic
      wounds. HBO reduces inflammation and accelerates wound healing, by mechanisms
      that remain unclear. Here we examined a mechanism by which HBO may reduce
      neutrophil recruitment, through changes in endothelial and neutrophil adhesion
      molecule expression and function. Human umbilical vein endothelial cells and
      neutrophils were exposed to selected chronic wound conditions, comprising hypoxia
      in the presence of lipopolysaccharide and tumor necrosis factor-alpha, and then
      treated with HBO. We observed neutrophil adhesion to endothelial cells following
      treatment with chronic wound conditions, which was reversed by HBO treatment.
      This was partly explained by reduced expression of endothelial intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 by HBO. No changes in
      neutrophil adhesion molecule expression (CD18, CD11b, CD62L, CD31) were observed
      following HBO treatment. However, HBO decreased hydrogen peroxide generation by
      neutrophils, and induced nitrous oxide-related protein modifications. The
      transnitrosating agent S-nitroso-L-cysteine ethyl ester (600 MUM) also reduced
      neutrophil adhesion to human umbilical vein endothelial cell monolayers, and the
      iNOS inhibitor 1400 W (10 MUM) and HgCl2, which promotes the decomposition of S
      nitrosothiols (1 mM), reversed the effect of HBO, suggesting that S-nitrosation
      may inhibit neutrophil-endothelial cell adhesion. This study indicates that HBO
      could reduce inflammation in wounds through reduced neutrophil recruitment,
      mediated by S-nitrosation.

PMID- 24134225
TI  - Ecological and evolutionary implications of food subsidies from humans.
AB  - Human activities are the main current driver of global change. From hunter
      gatherers through to Neolithic societies-and particularly in contemporary
      industrialised countries-humans have (voluntarily or involuntarily) provided
      other animals with food, often with a high spatio-temporal predictability.
      Nowadays, as much as 30-40% of all food produced in Earth is wasted. We argue
      here that predictable anthropogenic food subsidies (PAFS) provided historically
      by humans to animals has shaped many communities and ecosystems as we see them
      nowadays. PAFS improve individual fitness triggering population increases of
      opportunistic species, which may affect communities, food webs and ecosystems by
      altering processes such as competition, predator-prey interactions and nutrient
      transfer between biotopes and ecosystems. We also show that PAFS decrease
      temporal population variability, increase resilience of opportunistic species and
      reduce community diversity. Recent environmental policies, such as the regulation
      of dumps or the ban of fishing discards, constitute natural experiments that
      should improve our understanding of the role of food supply in a range of
      ecological and evolutionary processes at the ecosystem level. Comparison of
      subsidised and non-subsidised ecosystems can help predict changes in diversity
      and the related ecosystem services that have suffered the impact of other global
      change agents. 

PMID- 24134302
TI  - Causal knowledge in evidence-based medicine. In reply to Kerry et al.'s causation
      and evidence-based practice: an ontological review.
AB  - In Causation and evidence-based practice: an ontological review, Kerry et al.
      argue that evidence-based practice (EBP) should revise its understanding of
      causation, and take on board a dispositionalist ontology. We point out that the
      challenges from complexity discussed by Kerry et al., are not properly addressed
      by their proposed ontology. Rather, the difference making views of causation
      Kerry et al. criticize, spell out the relevant aspects of causation, and have a
      range of advantages compared to dispositionalist accounts. We explore some of
      these here, with a special focus on the role of causal assumptions in inferences
      from scientific evidence to clinical decisions. A philosophical account should
      help us explicate the assumptions that go into causal inference in EBM. In doing
      so, it enables an understanding of the various ways in which these assumptions
      might fail, and of how they can be justified. 

PMID- 24134303
TI  - Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS
      copolymer for breast cancer treatment.
AB  - A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d
      alpha-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer
      was developed for paclitaxel delivery for breast cancer treatment, which
      demonstrated superior in vitro and in vivo performance in comparison with
      paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear
      PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were
      fabricated by a modified nanoprecipitation method and then characterized in terms
      of size, surface charge, surface morphology, drug encapsulation efficiency, and
      in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical
      in shape with an average size of around 120 nm. The nanoparticles were found to
      be stable, showing no change in the particle size and surface charge during 90
      day storage of the aqueous solution. The release profiles of the paclitaxel
      loaded nanoparticles exhibited typically biphasic release patterns. The results
      also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy
      than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In
      conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block
      copolymer could be considered as a potentially promising and effective strategy
      for breast cancer treatment. 

PMID- 24134304
TI  - Hypertension is associated with serologically active disease in patients with
      systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative
      stress.
AB  - OBJECTIVES: To determine whether disease activity verified by laboratorial
      parameters is associated with a higher frequency of hypertension in patients with
      systemic lupus erythematosus (SLE) without renal impairment and to investigate
      factors that could influence this hypertension. METHOD: This study included 102
      controls, 70 patients with inactive SLE, and 53 patients with active SLE without
      renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines,
      nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS:
      Patients with active SLE had a higher probability of developing hypertension
      compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806
      8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752,
      p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p <
      0.05) than both controls and inactive SLE patients. Protein oxidation was
      significantly higher in patients with active SLE than in the control group and in
      patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate
      analysis revealed an association between the presence of hypertension and he
      levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p =
      0.0221), IFN-gamma (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373),
      IFN-gamma/IL-10 (p = 0.0142), IFN-gamma/IL-4 (p = 0.0320), and adiponectin (p =
      0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an
      increased frequency of high blood pressure (43.4%) compared with patients with
      inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with
      serologically active disease and was influenced by an increased Th1/Th2 ratio and
      oxidative stress.

PMID- 24134305
TI  - Coexistence of psoriasis vulgaris and vitiligo with bullous pemphigoid: a case
      report.

PMID- 24134306
TI  - Voices from the Hilo Women's Health Study: talking story about menopause.
AB  - Our purpose in conducting this qualitative study was to examine how a multiethnic
      sample of women living in Hilo, Hawai'i, describe menopause. Interviews were
      conducted with 185 pre-, peri-, and post-menopausal women aged 45 to 55. We found
      that pre-menopausal women felt anxious compared with peri- and post-menopausal
      women's more affirmative attitudes of increasing confidence and freedom in this
      new cycle of life. A dominant theme was the construction of a post-menstrual
      identity. Peri-and post-menopausal women's attitudes were not biomedically
      oriented. Local culture and the island lifestyle may provide a positive
      atmosphere for women going through menopause. 

PMID- 24134307
TI  - Henoch-Schonlein purpura in children.
AB  - Henoch-Schonlein purpura is the most common systemic vasculitis of childhood. In
      the majority of children, the outcome of Henoch-Schonlein purpura is excellent
      with spontaneous resolution of symptoms and signs. However, a small subset of
      patients will develop long-term sequelae in the form of chronic kidney disease.
      While the clinical presentation and diagnosis of Henoch-Schonlein purpura is
      straightforward, treatment of Henoch-Schonlein purpura nephritis and long-term
      renal outcomes of more severely affected children are less certain. This review
      article gives a general overview of Henoch-Schonlein purpura with emphasis on
      recently published information, including the new classification of childhood
      vasculitis, insights into pathogenesis of Henoch-Schonlein purpura and a summary
      of various treatments of established Henoch-Schonlein purpura nephritis. 

PMID- 24134308
TI  - A study of clinical profiles of vitiligo in different ages: an analysis of 669
      outpatients.
AB  - INTRODUCTION: Vitiligo is a skin disorder characterized by achromic macules
      (white) on the skin and/or mucous membranes, which affects 0.5-2% of the
      population. Few publications address a vitiligo epidemiological profile
      worldwide. In Brazil there are only studies in children. OBJECTIVE: To assess the
      clinical and epidemiological profile of individuals affected by vitiligo and to
      evaluate behavior of the disease in different age groups. MATERIALS AND METHODS:
      We conducted a retrospective cross-sectional study in 669 patients with vitiligo
      from January 2001 to May 2006, who attended the Faculty of Medicine of ABC,
      located in the metropolitan region of Sao Paulo, Brazil. RESULTS: There was a
      predominance of females (62.2%) and adult age group (62.5%), with higher
      prevalence peaks between the second and third decades of life (18.3% and 16.9%,
      respectively). The most frequent phototype in skin was III (49.9%). Lesions began
      on the face most commonly in children and adolescents (32.6%) and the elderly
      (23.3%), and on hands in adults (24.0%). There was a higher prevalence of
      segmental vitiligo in children and adolescents (36.4%), compared with adults
      (11.3%) and the elderly (6.7%), and vitiligo with stable evolution was
      proportionately more frequent in childhood and adolescents (46.2%) than in adults
      (32.5%) and elderly (36.7%). CONCLUSIONS: Our findings are similar to other
      countries, mainly regarding the higher prevalence of segmental vitiligo and
      vitiligo with stable development among children and adolescents.

PMID- 24134309
TI  - Open surgical partial nephrectomy for upper tract urothelial carcinoma.
AB  - We aimed to determine the ability of partial nephrectomy to prevent end-stage
      renal disease and tumor recurrence or progression in patients with upper tract
      urothelial carcinoma. Retrospectively, eight patients undergoing partial
      nephrectomy for upper tract urothelial carcinoma were identified and their
      medical records reviewed. All patients had imperative indications for nephron
      sparing, and diagnosis of upper tract urothelial carcinoma not adequately
      amenable to endoscopic management. Although three patients suffered acute tubular
      necrosis, only one required postoperative hemodialysis. During the follow-up
      period 25% (2/8) developed end-stage renal disease, including the one patient who
      had received postoperative hemodialysis. Recurrences occurred in five of seven
      patients with adequate oncological surveillance. Recurrences were successfully
      treated endoscopically in 80% (4/5) patients, and one patient had metastases. Of
      the eight patients, four have died. Death occurred 4 months, 1 year, 1.2 years
      and 3.5 years after partial nephrectomy. Of these patients, one succumbed to
      metastatic disease; the exact cause of death is unknown in the other three, but
      there was no documentation of metastatic cancer. The mean duration of follow up
      in the remaining four patients, all without evidence of metastatic urothelial
      cancer, is 71 months (range 22-108 months). In summary, partial nephrectomy for
      upper tract urothelial carcinoma in patients with imperative indications averts
      end-stage renal disease in most patients, and appears to be associated with
      acceptable disease-specific survival. Partial nephrectomy is a sparingly used
      option in patients with upper tract urothelial carcinoma refractory to endoscopic
      management who have imperative indications for nephron sparing. 

PMID- 24134311
TI  - A novel RCE1 isoform is required for H-Ras plasma membrane localization and is
      regulated by USP17.
AB  - Processing of the 'CaaX' motif found on the C-termini of many proteins, including
      the proto-oncogene Ras, requires the ER (endoplasmic reticulum)-resident protease
      RCE1 (Ras-converting enzyme 1) and is necessary for the proper localization and
      function of many of these 'CaaX' proteins. In the present paper, we report that
      several mammalian species have a novel isoform (isoform 2) of RCE1 resulting from
      an alternate splice site and producing an N-terminally truncated protein. We
      demonstrate that both RCE1 isoform 1 and the newly identified isoform 2 are
      required to reinstate proper H-Ras processing and thus plasma membrane
      localization in RCE1-null cells. In addition, we show that the deubiquitinating
      enzyme USP17 (ubiquitin-specific protease 17), previously shown to modulate RCE1
      activity, can regulate the abundance and localization of isoform 2. Furthermore,
      we show that isoform 2 is ubiquitinated on Lys43 and deubiquitinated by USP17.
      Collectively, the findings of the present study indicate that RCE1 isoform 2 is
      required for proper 'CaaX' processing and that USP17 can regulate this via its
      modulation of RCE1 isoform 2 ubiquitination. 

PMID- 24134312
TI  - Tinea capitis mimicking dissecting cellulitis.
AB  - Tinea capitis is a common disease of childhood that typically follows one of
      several clinical patterns. Our patient and several previously reported cases
      demonstrate the existence of a dissecting cellulitis-like presentation of tinea
      capitis. This variant should be recognized to prevent misdiagnosis of dissecting
      cellulitis and allow proper treatment to prevent scarring alopecia. 

PMID- 24134313
TI  - Introduction to the special section on communication and wartime deployment.
AB  - Over the past decade, the wars in Iraq and Afghanistan have taken a heavy toll on
      the physical, psychological, and relational health of military service members
      and their families. The articles included in this special section of Health
      Communication add to the robust, interdisciplinary body of research on the health
      consequences of wartime deployment by examining how communication enables the
      recovery process of service members and their families. Because communication
      processes can signal health problems, construct and promote family resiliency,
      and shape the content and delivery of health interventions, our discipline's
      theory and research can help inform ongoing efforts to support military families
      as the wars in Iraq and Afghanistan wind down. 

PMID- 24134314
TI  - Risk compensation behaviours in construction workers' activities.
AB  - The purpose of this study was to test whether the construction workers have the
      tendency of engaging in risk compensation behaviours, and identify the
      demographic variables, which may influence the extent to which the construction
      workers may show risk compensation behaviours. Both quantitative (survey) and
      qualitative (interviews) approaches were used in this study. A questionnaire
      survey was conducted with all the construction workers on three building
      construction sites of a leading construction company in Australia. Semi
      structured interviews were then conducted to validate the findings of the
      quantitative research. The findings indicate that workers tend to show risk
      compensation behaviours in the construction environment. The workers with more
      working experience, higher education, or having never been injured at work before
      have a higher tendency to show risk compensation in their activities than the
      others. The implication is that contractors need to assess the potential
      influence of workers' risk compensation behaviours when evaluating the effect of
      risk control measures. It is recommended that supervisors pay more attention to
      the behavioural changes of those workers who have more experience, higher
      education, and have never been injured before after the implementation of new
      safety control measures on construction site. 

PMID- 24134315
TI  - Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic
      mucosa defined by CD207 dendritic cells and CD209 macrophages.
AB  - A common route for HIV-1 infection is sexual transmission across colorectal
      mucosa, which is thought to be 10-2,000 times more vulnerable to infection than
      that of the female genital tract. Mucosal surfaces are the first line of defense
      against many pathogens but the antigen-presenting cells (APCs), key regulators of
      innate immunity and determinants of adaptive immunity, are not well defined in
      these target tissues. Using immunohistochemistry, dendritic cells expressing
      Langerin (CD207(+)), a lectin known to bind and internalize HIV-1, were detected
      in the periphery of colonic glands and sparsely scattered in the submucosa
      similarly in colorectal mucosa. This cell type, well known in skin, has generally
      not been reported in colonic/rectal mucosa. Unexpectedly, the largest APC
      population observed was a macrophage-like population expressing the well
      characterized tissue macrophage markers CD68 and CD163. Confocal microscopy of
      these cells revealed colocalization of CD209 (DC-SIGN), a presumed dendritic cell
      marker believed to facilitate HIV-1 transmission, but not other dendritic cell
      markers. These results show evidence of the unconfirmed presence of Langerhans
      cells in colorectal mucosa and a predominance of macrophage-like APCs that
      express CD209 (DC-SIGN). These findings define potential target cells in the
      pathogenesis of HIV-1 transmission, which may have key implications for the study
      of early transmission events in normal colorectal mucosa, as well as other
      infectious diseases and primary immune diseases involving the gut.

PMID- 24134317
TI  - Recipient graft failure or death impact on living kidney donor quality of life
      based on the living organ donor network database.
AB  - BACKGROUND AND PURPOSE: There is a paucity of prospective long-term data on
      living kidney donor (LKD) quality of life (QoL). The Living Organ Donor Network
      (LODN) database follows donors longitudinally and cross-references with United
      Network for Organ Sharing (UNOS) data to assess factors that affect donor QoL.
      PATIENTS AND METHODS: The Short Form (SF)-36 was sent to donors at 6 months and
      yearly thereafter. Recipient outcomes were determined from the UNOS database. Of
      2219 donors, 1030 returned >= 1 QoL survey in the first year. Seven-hundred and
      thirty-one donors returned at least two surveys with 51 associated with a
      nonfunctioning graft and 38 with recipient death. RESULTS: Initial QoL scores
      were not different between donors whose recipients were alive with graft
      function, and those whose recipients died (88.9 vs 89.2, P = 0.87). For donors
      whose recipient died, QoL in the year after recipient death averaged 6 points
      lower than the initial QoL (88.9 vs 82.9, P = 0.01). Thirty-one donors returned
      surveys an average of 4.1 years after their recipient's death. Final QoL score
      increased by 2.5 points, no longer significantly lower than the initial QoL (85.4
      vs 88.9, P = 0.16). Thirty-eight donors returned surveys in the year after their
      recipient's graft failure and their QoL decreased by 5.6 points on average (86.9
      vs 81.2, P = 0.07). Twenty-eight of these donors returned future surveys and
      final QoL was unchanged (81.2 vs 81.2, P = 0.99). CONCLUSIONS: Donor QoL declines
      after recipient death but recovers with time. Graft failure resulted in decreased
      QoL without recovery. The LODN database identifies factors affecting LKD QoL and
      provides a model for a national registry.

PMID- 24134316
TI  - Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant
      yeast assay and Ames test.
AB  - BACKGROUND: Crotalaria pallida Ailton is a plant belonging to the Fabaceae
      family, popularly known as "rattle or rattlesnake" and used in traditional
      medicine to treat swelling of the joints and as a vermifuge. Previous
      pharmacological studies have also reported anti-inflammatory, antimicrobial and
      antifungal activities. Nevertheless, scientific information regarding this
      species is scarce, and there are no reports related to its possible estrogenic
      and mutagenic effects. Thus, the purpose of the present study was to investigate
      the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast
      Assay (RYA), seeking an alternative for estrogen replacement therapy during
      menopause; and to reflect on the safe use of natural products to assess the
      mutagenic activity of the crude extract from C. pallida leaves, the
      dichloromethane fraction and stigmasterol by means of the Ames test. METHODS: The
      recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was
      performed with the ethanolic extract, dichloromethane fraction and stigmasterol
      isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the
      Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester
      strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization,
      by the preincubation method. RESULTS: All samples showed estrogenic activity,
      mainly stigmasterol. The ethanolic extract from C. pallida leaves showed
      mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and
      stigmasterol were found devoid of activity. CONCLUSION: Considering the excellent
      estrogenic activity performed by stigmasterol in the RYA associated with the
      absence of mutagenic activity when evaluated by the Ames test, stigmasterol
      becomes a strong candidate to be used in hormone replacement therapy during
      menopause.

PMID- 24134318
TI  - Microdeformation in wound healing.
AB  - Mechanical forces greatly influence cellular organization and behavior. Cells
      respond to applied stress by changes in form and composition until a suitable
      state is reestablished. However, without any mechanical stimuli cells stop
      proliferating, discontinue migration, go into cell-cycle arrest, and eventually
      die. Hence, one can assume that pathologies closely depending on cell migration
      like cancer or atherosclerosis might be governed by biophysical parameters.
      Moreover, mechanical cues will have fundamental effects in wound healing.
      Especially negative pressure wound therapy has the potential to endorse wound
      healing by induction of both macrodeformation (wound contraction) and
      microdeformation (tissue reactions at microscopic level). So far, the capacity
      for researchers to study the link between mechanical stimulation and biological
      response has been limited by the lack of instrumentation capable of stimulating
      the tissue in an appropriate manner. However, first reports on application of
      micromechanical forces to wounds elucidate the roles of cell stretch, substrate
      stiffness, and tissue deformation during cell proliferation and differentiation.
      This review deals with their findings and tries to establish a link between the
      current knowledge and the questions that are essential to clinicians in the
      field: What is the significance of mirodeformations for wound healing? Does "dead
      space" impede propagation of mechanical cues? How can microdeformations induce
      cell proliferation? What role do fibroblasts, myofibroblasts, and mesenchymal
      stem cells play in chronic wounds with regard to micromechanical forces? 

PMID- 24134319
TI  - Direct estimation of mass flow and diffusion of nitrogen compounds in solution
      and soil.
AB  - Plant nutrient uptake from soil is mainly governed by diffusion and
      transpirationally induced mass flow, but the current methods for assessing the
      relative importance of these processes are indirect. We developed a microdialysis
      method using solutions of different osmotic potentials as perfusates to simulate
      diffusion and mass flow processes, and assessed how induced mass flow affected
      fluxes of nitrogen (N) compounds in solution and in boreal forest soil. Varying
      the osmotic potential of perfusates induced vertical fluxes in the direction of
      the dialysis membranes at rates of between 1 * 10(-8) and 3 * 10(-7)  m s(-1) ,
      thus covering the estimated range of water velocities perpendicular to root
      surfaces and induced by transpiration. Mass flow increased N fluxes in solution
      but even more so in soil. This effect was explained by an indirect effect of mass
      flow on rates of diffusive fluxes, possibly caused by the formation of steeper
      gradients in concentrations of N compounds from membrane surfaces out in the
      soil. Our results suggest that transpiration may be an essential driver of plant
      N acquisition. 

PMID- 24134320
TI  - What does this mean for graduate education in marriage and family therapy?
      Commentary on "The divide between 'evidenced-based' approaches and practitioners
      of traditional theories of family therapy".
AB  - The Dattilio, Piercy, and Davis article is a welcome addition to the conversation
      focusing on how to bridge the divide in the MFT field between research and
      practice. The present commentary challenges us to see the divide as an indictment
      of our training programs resulting from a lack of focus on MFT research.
      Suggestions for increasing expectations for students to monitor client progress,
      get involved in research at all levels, and for doctoral students to expect to be
      able to conduct independent, fundable research in the MFT field when they leave
      their programs are offered. 

PMID- 24134321
TI  - Increased ubiquitination and the crosstalk of G protein signaling in cardiac
      myocytes: involvement of Ric-8B in Gs suppression by Gq signal.
AB  - Hyperactivation of Gq signaling causes cardiac hypertrophy, and beta-adrenergic
      receptor-mediated Gs signaling is attenuated in hypertrophic cardiomyocytes.
      Here, we found the increase in a global ubiquitination in hypertrophic mouse
      heart. The activation of Gq signaling resulted in the ubiquitination of Galphas
      in neonatal rat cardiomyocytes, reduced Galphas expression, and suppressed cAMP
      response to beta-adrenergic receptor stimulation. Ectopic expression of Galphaq
      induced a similar suppression, which is due to the degradation of Galphas by a
      ubiquitin-proteasome pathway. Co-expression of Ric-8B, a positive regulator of
      Galphas, effectively canceled the Galphaq-induced ubiquitination of Galphas and
      recovered the cAMP accumulation. In vitro, Galphaq competes for the binding of
      Galphas to Ric-8B. These data show a new role of Ric-8B in the crosstalk of two
      distinct G protein signaling pathways, which are possibly involved in a part of
      mechanisms of chronic heart failure. 

PMID- 24134322
TI  - Thermo-cross-linked elastomeric opal films.
AB  - An efficient and convenient thermal cross-linking protocol in elastomeric opal
      films leading to fully reversible and stretch-tunable optical materials is
      reported. In this study, functional monodisperse core-shell particles were
      arranged in a face-centered cubic (fcc) lattice structure by a melt flow process.
      A problem up to now was that un-cross-linked films could not be drawn fully
      reversibly and hence lost their optical and mechanical performance. After thermal
      cross-linking reaction, the obtained films can be drawn like rubbers and the
      color of their Bragg reflection changes because of controlled lattice
      deformation, which makes the cross-linked films mechanochromic sensors. Different
      techniques were developed for the cross-linking of the films a posteriori, after
      their preparation in the melt flow process. A photo-cross-linking approach was
      reported earlier. This study now deals with a very efficient thermo-cross-linking
      approach based on the chemistry of hydroxyl- and isocyanate-functionalities that
      form urethane bridges. The focus of the present work is the mechanism and
      efficiency of this cross-linking process for elastomeric opal films with
      excellent mechanical and optical properties. 

PMID- 24134323
TI  - Interleukin-18 as an efficient marker for remission and follow-up in patients
      with inactive adult-onset Still's disease.
AB  - OBJECTIVES: Diagnosis of adult-onset Still's disease (AOSD) is difficult because
      of a lack of pathognomonic findings and markers. The aim of this study was to
      investigate the efficacy of interleukin (IL)-18 and free IL-18 in the diagnosis
      and follow-up of patients with AOSD. METHOD: Levels of inflammatory cytokines, IL
      18, IL-18 binding protein (IL-18BP), and free IL-18 were compared in 80 AOSD
      patients and 90 controls. The AOSD patients were divided into active and inactive
      groups according to disease activity, and the inactive patients were subdivided
      into a remission subgroup and a low disease activity subgroup. We compared
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, IL-18,
      and free IL-18 as disease activity markers in the AOSD patients. Serial serum
      levels of activity markers were measured in 52 of the 80 AOSD patients at 3- to 6
      month intervals. RESULTS: There were significantly higher levels of IL-18 and
      free IL-18 in the AOSD patients than in the controls. IL-18 and free IL-18 were
      significantly higher in the active group than the inactive group (p < 0.001 for
      all). Unlike other activity markers, IL-18 and free IL-18 levels in the low
      disease activity subgroup were significantly higher than those in the remission
      subgroup within the inactive group (p = 0.004 and 0.005, respectively). During
      serial follow-up, ferritin and IL-18 showed a significant decrease in the
      responder and remission subgroup. CONCLUSIONS: IL-18 might be an efficient marker
      for diagnosis and follow-up of AOSD and might also be a useful predictor of
      remission, especially in clinically inactive patients.

PMID- 24134324
TI  - Comparison of cystatin C and Beta-2-microglobulin kinetics in children on
      maintenance hemodialysis.
AB  - Middle-molecules (MM) are not monitored in children on hemodialysis (HD), but are
      accumulated and increase the risk of cardiovascular disease and mortality.
      Molecular properties of Cystatin C (CyC), 13 kDa, potentially make it a preferred
      MM marker over Beta-2-Microglobulin (B2M), 12 kDa. We compared CyC and B2M
      kinetics to investigate if CyC can be used as preferred MM marker. CyC (mg/L) and
      B2M (MUg/mL) were measured in 21 low-flux HD sessions in seven children. Blood
      samples were taken at HD start (pre), 1 and 2 hours into HD and at end of HD
      (post) for all sessions and 60 minutes after the first HD (Eq). PreCyC (9.85 +/-
      2.15) did not differ (P > 0.05) from postCyC (10.04 +/- 2.83). PostB2M (38.87 +/-
      7.12) was higher (P < 0.05) than preHD B2M (33.27 +/- 7.41). There was no change
      in CyC at 1 and 2 hours into HD, while B2M progressively increased. CyC or B2M
      changes did not significantly correlate with spKt/V (2.09 +/- 0.86),
      ultrafiltration (4.61 +/- 1.98%) or HD duration (218 +/- 20 minutes). EqCyC was
      not different from postCyC (11.07 +/- 3.14 vs. 10.71 +/- 2.85, P > 0.05), while
      EqB2M was lower than postB2M (36.48 +/- 7.68 vs. 41.09 +/- 8.99, P < 0.05). MMs
      as represented by B2M and CyC are elevated in children on standard HD.
      Intensified HD modalities would be needed for their removal. B2M is affected by
      the dialytic process with a rise during HD independent of ultrafiltration and
      decrease 1 hour after, while CyC remains unchanged. We suggest that CyC be used
      as preferred marker of MM removal and as a marker of adequacy of intensified HD
      regimens.

PMID- 24134325
TI  - Vascular calcification in end-stage renal disease.
AB  - Vascular calcification is highly prevalent in end-stage renal disease and
      independently predictive of future cardiovascular events and mortality.
      Calcification can occur in both the intimal and medial layers of vasculature, but
      medial calcification is the major form in end-stage renal disease. Medial
      calcification increases large elastic artery stiffness and pulse-pressure,
      promotes left ventricular hypertrophy, reduces perfusion of the coronary
      arteries, and ultimately promotes increased cardiovascular mortality via
      increased risk of myocardial infarction and heart failure. It results not from a
      passive deposition of calcium and phosphate due to increased circulating levels,
      but rather is an active cell-mediated process involving vascular smooth muscle
      cell apoptosis and vesicle release, a shift in the balance of inhibitors and
      promoters of vascular calcification, and vascular smooth muscle cell
      differentiation from a contractile to osteochondrogenic phenotype. This
      phenotypic shift requires phosphate, as well as the uptake of phosphate by the
      sodium-dependent phosphate cotransporter PiT-1, which is upregulated by
      proinflammatory cytokines and the uremic milieu. Further research is needed to
      determine if targeting these processes can ultimately reduce vascular
      calcification in this high cardiovascular risk population. 

PMID- 24134326
TI  - Efficacy of oral powder compared with chewable tablets for lanthanum carbonate
      administration in hemodialysis patients.
AB  - Lanthanum carbonate (LC) has been administered in a chewable tablet form for
      patients with hyperphosphatemia undergoing dialysis. However, some patients have
      difficulty chewing the tablets. LC oral powder has recently been released in
      Japan. The purpose of this study was to clarify the efficacy of LC oral powder
      form compared with that of chewable tablet form. The efficacy and safety of LC
      oral powder was retrospectively assessed in hemodialysis patients who switched
      from chewable tablet form to oral powder form without dose modification. Thirty
      six patients (mean age, 66.8 +/- 10.5 years; male, 64%; 39% with diabetes; mean
      duration of dialysis treatment, 99.2 +/- 95.6 months) were enrolled in this study
      between June and July of 2012. Changes in clinical data and adverse events after
      the switch to oral powder form were investigated. The average dose of LC was 1180
      +/- 520 mg/day. Serum phosphorus levels were significantly decreased after the
      switch from chewable tablet form to oral powder form (5.3 +/- 1.7 mg/dL at
      baseline vs. 4.9 +/- 1.2 mg/dL at after 1 month after, P = 0.038). In contrast,
      no significant differences were observed in serum calcium and parathyroid hormone
      levels. Furthermore, no significant differences were evident in weight gain after
      the switch to oral powder form (2.5 +/- 1.2 kg at baseline vs. 2.4 +/- 1.1 kg at
      1 month after the switch, P = 0.29). No serious adverse events were recorded. Our
      results suggest that LC is more effective in oral powder form than chewable
      tablet form for hemodialysis patients.

PMID- 24134327
TI  - Changing the hemodialysis prescription for hemodialysis patients with subdural
      and intracranial hemorrhage.
AB  - Although continuous modalities of renal replacement therapy offer an advantage to
      the patient with compromised cerebral perfusion and intracranial hypertension,
      they are generally limited to the intensive care unit setting. Many hemodialysis
      patients admitted with strokes and subdural hematoma are managed on general
      wards. As such, these patients are generally treated by intermittent
      hemodialysis, and their dialysis prescription should be altered to minimize
      changes in serum osmolality, and fall in blood pressure during dialysis. Such
      patients require more frequent but shorter dialysis sessions, using minimally
      bioincompatible small surface area dialyzers with lower blood flows, in
      combination with higher sodium and cooled dialysate. In patients at risk of
      intracranial hemorrhage and those with invasive intracranial monitoring, systemic
      anticoagulants should be avoided, choosing no anticoagulation protocols or
      regional anticoagulants. 

PMID- 24134328
TI  - The rationale for the use of low molecular weight heparin for hemodialysis
      treatments.
AB  - Unfractionated heparin (UFH) is the most commonly used anticoagulant for
      hemodialysis worldwide. However, UFH comprises a series of different molecules
      with variable biological activity, thus risking under and over anticoagulation.
      As such, low molecular weight heparins (LMWHs) were developed to improve
      reliability. LMWHs are now established in clinical practice and have been proven
      to be effective in preventing extracorporeal circuit clotting, but also safer
      with fewer reported bleeding episodes and less heparin induced thrombocytopenia
      than UFH. As with UFH, most centers simply adjust the dose of LMWHs by clinical
      inspection of the extracorporeal circuit for thrombus, and bleeding times post
      fistula needle removal. Despite potentially higher drug costs, LMWHs have become
      the anticoagulant of choice in Europe for routine outpatient hemodialysis
      sessions, due to their ease of administration and reliability of clinical effect.

PMID- 24134329
TI  - Calciphylaxis and subtotal parathyroidectomy: a double-edged sword.
AB  - Calciphylaxis, also called calcific uremic arteriolopathy is a dreadful, life
      threatening ischemic vasculopathy, primarily involving skin and subcutaneous
      tissue, mostly on patients with end-stage kidney disease. Calciphylaxis is a well
      described, but still a poorly understood disorder of mineral metabolism. Its
      occurrence is rare, but increasingly reported. We describe a 62-year-old obese
      lady on hemodialysis for end-stage kidney disease due to type 2 diabetes, who
      developed two episodes of calciphylactic skin lesions during the 3 years
      observation. The healing of lesions in the first episode was prompted by a
      subtotal parathyroidectomy for severe secondary hyperparathyroidism. However, the
      resumption of oral calcium and vitamin D analog for the parathyroidectomy-related
      hypocalcemia induced another occurrence of widespread calciphylactic skin lesions
      in areas of great adiposity. The typical regimen of IV sodium thiosulfate brought
      a successful outcome to the second episode. Now, growing numbers of successful
      treatment for calciphylaxis are reported with more specific therapies and a clear
      understanding of the pathogenetic mechanism is in sight. 

PMID- 24134330
TI  - Using noninvasive hemoglobin measurements to estimate measured hemoglobin in a
      pediatric hemodialysis unit.
AB  - Maintaining a dialysis patient's hemoglobin (Hgb) within a very narrow range can
      be challenging. Relying on Hgb measurements only once or twice a month can cause
      large fluctuations in their measurements. Utilizing the Hgb measurement from
      noninvasive modalities has been studied in adult populations. Our study focused
      on a pediatric hemodialysis population where blood volumes are much smaller to
      see if these measurements would adequately work for adjusting erythropoietin
      dosages. We reviewed our patients' data over a 6-month time period and collected
      simultaneous measurements of Hgb performed in the laboratory, as well as the
      initial Crit-Line measurement. We then analyzed the correlation of the two
      estimates of the patient's Hgb using linear regression as well as Bland-Altman
      plot and ROCs. There were 407 simultaneous measurements of Hgb in our 32
      pediatric hemodialysis patients during this time. Linear regression showed good
      correlation with an R value of 0.85 (P value < 0.0001). The Bland-Altman plot
      showed excellent agreement between the two methods. The ROC analysis showed that
      the performance of the noninvasive Hgb measurement was very good at predicting
      low measurements. Predicting Hgb less than 10 g/dL had an area under the curve of
      0.94. Predicting Hgb greater than 12 g/dL had an area under the curve of 0.91.
      There were 100 simultaneous measurements of hematocrit. The analysis revealed
      similar results as the hemoglobin. Noninvasive in-line monitoring of Hgb can be a
      very useful way of assessing the patient's response to erythropoietin on a day-to
      day time frame. Utilizing this methodology should help reduce the variability in
      the pediatric patients' Hgb measurements.

PMID- 24134331
TI  - Relationship status as an influence on cybersex activity: cybersex, youth, and
      steady partner.
AB  - The authors focus on the influence of participants' having or not having a steady
      partner when reference to cybersex use. Participants were 1,239 young, Spanish
      individuals who completed the Internet Sex Screening Test. Results showed the
      influence of being in a relationship on certain consumption dimensions of
      cybersex; the influence was found to be greater in men than in women. In general,
      cybersex activity was higher for single participants, although it was also
      significant for participants with a steady partner. The authors' findings
      facilitate the comprehension of the effect of new technologies in intimate human
      relationships. 

PMID- 24134332
TI  - Predicting species distributions for conservation decisions.
AB  - Species distribution models (SDMs) are increasingly proposed to support
      conservation decision making. However, evidence of SDMs supporting solutions for
      on-ground conservation problems is still scarce in the scientific literature.
      Here, we show that successful examples exist but are still largely hidden in the
      grey literature, and thus less accessible for analysis and learning. Furthermore,
      the decision framework within which SDMs are used is rarely made explicit. Using
      case studies from biological invasions, identification of critical habitats,
      reserve selection and translocation of endangered species, we propose that SDMs
      may be tailored to suit a range of decision-making contexts when used within a
      structured and transparent decision-making process. To construct appropriate SDMs
      to more effectively guide conservation actions, modellers need to better
      understand the decision process, and decision makers need to provide feedback to
      modellers regarding the actual use of SDMs to support conservation decisions.
      This could be facilitated by individuals or institutions playing the role of
      'translators' between modellers and decision makers. We encourage species
      distribution modellers to get involved in real decision-making processes that
      will benefit from their technical input; this strategy has the potential to
      better bridge theory and practice, and contribute to improve both scientific
      knowledge and conservation outcomes. 

PMID- 24134333
TI  - Synthesis and electroluminescence property of new hexaphenylbenzene derivatives
      including amine group for blue emitters.
AB  - Three new blue-emitting compounds of 5P-VA, 5P-VTPA, and 5P-DVTPA for organic
      light-emitting diode (OLED) based on hexaphenylbenzene moiety were demonstrated.
      Physical properties by the change of the substitution groups of the synthesized
      materials were systematically examined. Photoluminescence spectrum of the
      synthesized materials showed maximum emitting wavelengths of about 400 to 447 nm
      in solution state and 451 to 461 nm in film state, indicating deep blue emission
      color. OLED devices were fabricated by the synthesized compounds using vacuum
      deposit process as an emitting layer. The device structure was ITO/2-TNATA 60 nm/
      NPB 15 nm/ EML 35 nm/ TPBi 20 nm/ LiF 1 nm/ Al 200 nm. External quantum
      efficiencies and CIE values of 5P-VA, 5P-VTPA, and 5P-DVTPA were 1.89%, 3.59%,
      3.34%, and (0.154, 0.196), (0.150, 0.076), (0.148, 0.120), respectively. 5P-VTPA
      and 5P-DVTPA exhibited superior highly blue quality and thermal property such as
      high Td of 448 degrees C and 449 degrees C. 

PMID- 24134334
TI  - Effects of midazolam, pentobarbital and ketamine on the mRNA expression of ion
      channels in a model organism Daphnia pulex.
AB  - BACKGROUND: Over the last few decades intensive studies have been carried out on
      the molecular targets mediating general anesthesia as well as the effects of
      general anesthetics. The gamma-aminobutyric acid type A receptor (GABAAR) has
      been indicated as the primary target of general anaesthetics such as propofol,
      etomidate and isoflurane, and sedating drugs including benzodiazepines and
      barbiturates. The GABAAR is also involved in drug tolerance and dependence.
      However, the involvement of other ion channels is possible. METHODS: Using
      reverse transcription and quantitative PCR techniques, we systematically
      investigated changes in the mRNA levels of ion channel genes in response to
      exposure to midazolam, pentobarbital and ketamine in a freshwater model animal,
      Daphnia pulex. To retrieve the sequences of Daphnia ion channel genes, Blast
      searches were performed based on known human or Drosophila ion channel genes.
      Retrieved sequences were clustered with the maximum-likelihood method. To
      quantify changes in gene expression after the drug treatments for 4 hours, total
      RNA was extracted and reverse transcribed into cDNA and then amplified using
      quantitative PCR. RESULTS: A total of 108 ion channel transcripts were examined,
      and 19, 11 and 11 of them are affected by midazolam (100 MUM), pentobarbital (200
      MUM) and ketamine (100 MUM), respectively, covering a wide variety of ion channel
      types. There is some degree of overlap with midazolam- and pentobarbital-induced
      changes in the mRNA expression profiles, but ketamine causes distinct changes in
      gene expression pattern.In addition, flumazenil (10 MUM) eliminates the effect of
      midazolam on the mRNA expression of the GABAA receptor subunit Rdl, suggesting a
      direct interaction between midazolam and GABAA receptors. CONCLUSIONS: Recent
      research using high throughput technology suggests that changes in mRNA
      expression correlate with delayed protein expression. Therefore, the mRNA profile
      changes in our study may reflect the molecular targets not only in drug actions,
      but also in chronic drug addiction. Our data also suggest the possibility that
      hypnotic/anesthetic drugs are capable of altering the functions of the nervous
      system, as well as those non-nerve tissues with abundant ion channel expressions.

PMID- 24134335
TI  - Prevention and treatment of intraluminal catheter thrombosis in children
      hospitalised in a paediatric intensive care unit.
AB  - AIM: The aim of the study was to develop and implement a protocol for the
      prevention and treatment of catheter related intraluminal thrombosis in a
      paediatric intensive care unit METHODS: A computerised search was carried out on
      MEDLINE, through PubMed, using the medical subject heading 'central venous
      catheter', 'central venous access device', 'central venous line' associated with
      'occlusion', 'obstruction', 'catheter-related thrombosis', 'critically ill
      patients' and 'thrombolytic therapy'. References of reviewed articles were also
      searched for relevant titles as well as non-randomised controlled trials and
      series of cases when no information of higher level of evidence was available.
      RESULTS: With the information gathered, a protocol for the prevention and
      treatment of catheter related intraluminal thrombosis was elaborated and those
      recommendations that best suit our environment were included. They were agreed
      upon by a broad panel of professionals working in the Pediatric Intensive Care
      Unit and the Pharmacy Department. CONCLUSIONS: Due to the variety of options
      available for the pharmacotherapeutic management of intraluminal catheter
      thrombosis, one measure to improve the quality of the therapy and to diminish the
      variability in the prescription could be the implementation of a protocol as
      described in this paper.

PMID- 24134336
TI  - Minute reddish patch of extramammary Paget's disease with notable lymph node
      metastases.

PMID- 24134337
TI  - Clinical characteristics and prostate-specific antigen kinetics of prostate
      cancer detected in repeat annual population screening in Japan.
AB  - OBJECTIVES: To clarify the present status regarding repeat examination in the
      annual population screening system in Japan, and to analyze the clinical
      characteristics and prostate-specific antigen kinetics of prostate cancer
      detected in this setting. METHODS: We summarized the annual individual data of
      prostate-specific antigen-based population screening in Kanazawa, Japan, and
      analyzed the prostate cancer detection rates at first and repeat screening. The
      clinical characteristics were compared between patients detected at first and
      repeat screening. The patients were classified according to favorable or
      unfavorable clinical characteristics of cancer, and prostate-specific antigen
      kinetics were compared between the two groups. RESULTS: From 2000 to 2011, 19 620
      men participated in this screening program, and a total of 59 019 screenings were
      carried out. The total annual numbers of examinees increased, and the annual
      rates of first examinees gradually decreased. The annual detection rates of
      cancer at total screening decreased in the second year. The annual detection rate
      at first screening was not different from that in the first year. The rate of
      patients with favorable cancer features was significantly higher among patients
      detected at repeat screening than at first screening. The rates of patients with
      high prostate-specific antigen velocity and low prostate-specific antigen
      doubling time were significantly higher in unfavorable than favorable cancer
      patients in repeat screening. CONCLUSIONS: Repeat population screening could
      contribute to early detection of prostate cancer, and it seems that prostate
      specific antigen kinetics might predict the cancer characteristics in repeat
      screening.

PMID- 24134338
TI  - Post waxing folliculitis: a clinicopathological evaluation.
AB  - BACKGROUND: Epilation by waxing is one of the common methods of removing unwanted
      body hair, and follicular papules following this cosmetic procedure are not
      uncommon. However, this not so uncommon problem has not been clinically and
      histopathologically evaluated. OBJECTIVE: To study the clinicopathological
      profile of folliculitis temporally developing after epilation by waxing. SUBJECTS
      AND METHODS: Clinical and histopathological evaluation was done in 28 patients
      who developed follicular papules within a period of eight weeks following a
      history of epilation by waxing over the same area. The demographic profile and
      the method and frequency of waxing were noted. The symptoms associated with and
      the morphology and distribution of the follicular lesions were recorded. A punch
      biopsy was done from a representative follicular lesion to evaluate the
      pathological changes. RESULTS: All the patients recruited were females (100%)
      with a mean age of 24.33 + 2.43 years. While all 28 patients had waxed their
      forearms, 25 had waxed their arms, 18 their legs, and 10 their thighs. The most
      common sites affected by folliculitis were arms (25; 100%) and forearms (15/28;
      53.6%). Thighs, though least frequently waxed, were involved in seven (70%)
      subjects. Of these, seven (25%) women complained of itching. The lesions in all
      patients were erythematous to skin colored follicular papules, though two (7.1%)
      patients also had nodular lesions. A punch biopsy done showed features suggestive
      of pseudofolliculitis. A granulomatous reaction was seen in nine (32.1%)
      biopsies. A foreign body identified as a hair shaft was seen in seven (25%)
      biopsies and keratin in one biopsy. CONCLUSIONS: Folliculitis following epilation
      by waxing is more frequent in proximal parts of the extremities than in distal
      parts, even though distal parts are more frequently waxed. In one-third of the
      cases, post-waxing folliculitis is due to foreign body reaction to hair shaft or
      keratin and resembles pseudofolliculitis. To know exact pathogenesis, additional
      biopsies with multiple step sections need to be taken to look for retained
      fragments of hair shaft and /or foreign body reaction.

PMID- 24134339
TI  - Distinguishing Personality Psychopathology Five (PSY-5) characteristics
      associated with violent and nonviolent juvenile delinquency.
AB  - This study examined the relationship between the Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-A) Personality Psychopathology Five (PSY
      5) scales and violent and nonviolent juvenile delinquency. Participants were 260
      adolescent boys and girls in a forensic setting. Results indicated that
      Disconstraint (DISC), a marker of behavioral disinhibition and impulsivity, was
      associated with nonviolent delinquency, whereas Aggressiveness (AGGR), which is
      characterized by the use of instrumental aggression and interpersonal dominance,
      was specifically associated with violent delinquency. These findings are
      consistent with expectations based on empirical findings in the broader
      personality literature linking the construct of disinhibition with externalizing
      psychopathology as well as the literature identifying callous-unemotional
      aggression as a risk factor for violence. 

PMID- 24134340
TI  - The novel HLA-A*26:89 allele identified by sequence-based typing.

PMID- 24134341
TI  - Public health or private profit?

PMID- 24134342
TI  - Biomarker evidence of tobacco smoke exposure in children participating in lead
      screening.
AB  - OBJECTIVES: We assessed tobacco smoke exposure (TSE), defined according to
      detection of cotinine, in dried blood spots collected from children for lead
      screening. METHODS: Dried blood spots collected from a national sample of 1541
      Black and White children and submitted to a commercial laboratory for lead
      analysis were analyzed for cotinine. We used an anonymous administrative data set
      including information on children's characteristics to conduct univariate and
      multivariate analyses. RESULTS: Cotinine was detected in 61% of dried blood
      spots; 17% of samples had cotinine levels above 3 nanograms per gram. Median
      cotinine levels were significantly higher among Black than White children (0.66
      ng/g vs 0.30 ng/g) and among Medicaid recipients (0.94 ng/g vs < 0.3 ng/g). In
      multivariate analyses, significant increases in cotinine levels were associated
      with Black (vs White) race, older age, Medicaid coverage, higher state smoking
      rate, and higher average winter temperature. Detectable cotinine levels were
      significantly associated with higher lead levels. CONCLUSIONS: TSE is highly
      prevalent among children undergoing lead screening, and exposure levels are
      greater among Black children and children on Medicaid. TSE may contribute to lead
      exposure. Concurrent lead screening and biological screening for TSE may be a
      feasible approach to increasing childhood TSE detection.

PMID- 24134343
TI  - Impact of rurality, broiler operations, and community socioeconomic factors on
      the risk of campylobacteriosis in Maryland.
AB  - OBJECTIVES: We evaluated the combined impact of community-level environmental and
      socioeconomic factors on the risk of campylobacteriosis. METHODS: We obtained
      Campylobacter case data (2002-2010; n = 3694) from the Maryland Foodborne
      Diseases Active Surveillance Network. We obtained community-level socioeconomic
      and environmental data from the 2000 US Census and the 2007 US Census of
      Agriculture. We linked data by zip code. We derived incidence rate ratios by
      Poisson regressions. We mapped a subset of zip code-level characteristics.
      RESULTS: In zip codes that were 100% rural, incidence rate ratios (IRRs) of
      campylobacteriosis were 6 times (IRR = 6.18; 95% confidence interval [CI] = 3.19,
      11.97) greater than those in urban zip codes. In zip codes with broiler chicken
      operations, incidence rates were 1.45 times greater than those in zip codes
      without broilers (IRR = 1.45; 95% CI = 1.34, 1.58). We also observed higher rates
      in zip codes whose populations were predominantly White and had high median
      incomes. CONCLUSIONS: The community and environment in which one lives may
      significantly influence the risk of campylobacteriosis.

PMID- 24134344
TI  - Expanded HIV testing in the US Department of Veterans Affairs, 2009-2011.
AB  - OBJECTIVES: We measured HIV testing and seropositivity among veterans in Veterans
      Affairs (VA) care for calendar years 2009 through 2011 and analyzed 2011 results
      by patient demographics. METHODS: We performed a repeated-measures cross
      sectional study using standardized electronic data extraction from the VA
      electronic health records for all veterans with at least 1 outpatient visit
      during 2009 through 2011. We analyzed testing rates and seropositivity by
      demographic characteristics for 2011. RESULTS: Of veterans with an outpatient
      visit, 20.0% had an HIV test in 2011, compared with 9.2% in 2009. Documented HIV
      testing rates were highest in women and Blacks. Of confirmed positive test
      results, 67.0% were in outpatients older than 50 years. Seropositivity was
      highest among men aged 30 to 49 years, women aged 50 to 69 years, and Black
      outpatients of both genders. Implementation of an electronic clinical reminder
      was associated with higher testing rates. CONCLUSIONS: The significant effect of
      an electronic clinical reminder suggests that such decision support tools can
      substantially increase testing rates. The frequency of positive test results in
      older individuals suggests the need for additional work to define optimum
      approaches to HIV testing in this population.

PMID- 24134345
TI  - "You're an open target to be abused": a qualitative study of stigma and HIV self
      disclosure among Black men who have sex with men.
AB  - The HIV/AIDS epidemic is a health crisis among Black men who have sex with men
      (MSM). HIV-related stigma presents a primary barrier to sexual communication and
      effective HIV prevention. Using in-depth, qualitative interviews conducted with
      20 HIV-positive Black MSM between 2007 and 2008 in Chicago, Illinois, we explored
      the themes related to HIV-related stigma and the underlying messages HIV-positive
      Black MSM receive regarding their status. Stigmatizing messages stem from family,
      churches, and the gay community and from negative, internalized, beliefs HIV
      positive Black MSM held about infected individuals before their own infection.
      HIV stigma influences sexual silence around HIV disclosure, especially to sexual
      partners. 

PMID- 24134346
TI  - Scarcity of relevant data on traumatic brain injuries in youth sports.

PMID- 24134347
TI  - Ethical considerations for conducting health disparities research in community
      health centers: a social-ecological perspective.
AB  - Community health centers (CHCs) provide optimal research settings. They serve a
      high-risk, medically underserved population in the greatest need of intervention.
      Low socioeconomic status renders this population particularly vulnerable to
      research misconduct. Traditional principles of research ethics are often applied
      to participants only. The social-ecological model offers a comprehensive
      framework for applying these principles across multiple levels (participants,
      providers, organizations, communities, and policy). Our experience with the Trial
      Using Motivational Interviewing, Positive Affect and Self-Affirmation in African
      Americans with Hypertension, a randomized trial conducted in CHCs, led us to
      propose a new platform for discussing research ethics; examine the social,
      community, and political factors surrounding research conducted in CHCs; and
      recommend how future research should be conducted in such settings. 

PMID- 24134348
TI  - Harvey responds.

PMID- 24134349
TI  - Ethical research and minorities.

PMID- 24134350
TI  - Women's health initiative view of estrogen avoidance and all-cause mortality.

PMID- 24134351
TI  - Risk, reward, and the double-edged sword: perspectives on pharmacogenetic
      research and clinical testing among Alaska Native people.
AB  - OBJECTIVES: Pharmacogenetic research and clinical testing raise important
      concerns for individuals and communities, especially where past medical research
      and practice has perpetrated harm and cultivated distrust of health care systems
      and clinicians. We investigated perceptions of pharmacogenetics among Alaska
      Native (AN) people. METHODS: We held four focus groups for 32 ANs in south
      central Alaska to elicit views about pharmacogenetics in general and for
      treatment of cardiovascular disease, breast cancer, depression, and nicotine
      addiction. We analyzed data for perceived risks and rewards of pharmacogenetics.
      RESULTS: Potential risks of pharmacogenetics included health care rationing,
      misuse of information, and stigma to individuals and the AN community. Potential
      rewards included decreased care costs, improved outcomes, and community
      development. Participants also discussed 8 contingent conditions that could
      mitigate risks and increase pharmacogenetic acceptability. CONCLUSIONS: Alaska
      Natives perceive pharmacogenetics as potentially benefitting and harming
      individuals, communities, and health systems, depending on methods and oversight.
      Researchers, clinicians, and administrators, especially in community-based clinic
      and health care systems serving minority populations, must address this "double
      edged sword" to effectively conduct pharmacogenetics.

PMID- 24134352
TI  - Ethical community-engaged research: a literature review.
AB  - Health research has relied on ethical principles, such as those of the Belmont
      Report, to protect the rights and well-being of research participants. Community
      based participatory research (CBPR), however, must also consider the rights and
      well-being of communities. This requires additional ethical considerations that
      have been extensively discussed but not synthesized in the CBPR literature. We
      conducted a comprehensive thematic literature review and summarized empirically
      grounded discussions of ethics in CBPR, with a focus on the value of the Belmont
      principles in CBPR, additional essential components of ethical CBPR, the ethical
      challenges CBPR practitioners face, and strategies to ensure that CBPR meets
      ethical standards. Our study provides a foundation for developing a working
      definition and a conceptual model of ethical CBPR. 

PMID- 24134353
TI  - Shared decision-making for cancer care among racial and ethnic minorities: a
      systematic review.
AB  - To assess decision-making for cancer treatment among racial/ethnic minority
      patients, we systematically reviewed and synthesized evidence from studies of
      "shared decision-making," "cancer," and "minority groups," using PubMed,
      PsycInfo, CINAHL, and EMBASE. We identified significant themes that we compared
      across studies, refined, and organized into a conceptual model. Five major themes
      emerged: treatment decision-making, patient factors, family and important others,
      community, and provider factors. Thematic data overlapped categories, indicating
      that individuals' preferences for medical decision-making cannot be authentically
      examined outside the context of family and community. The shared decision-making
      model should be expanded beyond the traditional patient-physician dyad to include
      other important stakeholders in the cancer treatment decision process, such as
      family or community leaders. 

PMID- 24134355
TI  - Promoting physical activity through the shared use of school recreational spaces:
      a policy statement from the American Heart Association.
AB  - Most Americans are not sufficiently physically active, even though regular
      physical activity improves health and reduces the risk of many chronic diseases.
      Those living in rural, non-White, and lower-income communities often have
      insufficient access to places to be active, which can contribute to their lower
      level of physical activity. The shared use of school recreational facilities can
      provide safe and affordable places for communities. Studies suggest that
      challenges to shared use include additional cost, liability protection,
      communication among constituencies interested in sharing space, and decision
      making about scheduling and space allocation. This American Heart Association
      policy statement has provided recommendations for federal, state, and local
      decision-makers to support and expand opportunities for physical activity in
      communities through the shared use of school spaces. 

PMID- 24134354
TI  - The effectiveness of cigarette price and smoke-free homes on low-income smokers
      in the United States.
AB  - OBJECTIVES: We examined the effectiveness of state cigarette price and smoke-free
      homes on smoking behaviors of low-income and high-income populations in the
      United States. METHODS: We used the 2006-2007 Tobacco Use Supplement to the
      Current Population Survey. The primary outcomes were average daily cigarette
      consumption and successful quitting. We used multivariable regression to examine
      the association of cigarette price and smoke-free home policies on these
      outcomes. RESULTS: High state cigarette price (pack price >= $4.50) was
      associated with lower consumption across all income levels. Although low-income
      individuals were least likely to adopt smoke-free homes, those who adopted them
      had consumption levels and successful quit rates that were similar to those among
      higher-income individuals. In multivariable analysis, both policies were
      independently associated with lower consumption, but only smoke-free homes were
      associated with sustained cessation at 90 days. CONCLUSIONS: High cigarette
      prices and especially smoke-free homes have the potential to reduce smoking
      behaviors among low-income individuals. Interventions are needed to increase
      adoption of smoke-free homes among low-income populations to increase cessation
      rates and prevent relapse.

PMID- 24134356
TI  - Museums as a venue for public health intervention.
AB  - Big Food: Health, Culture, and the Evolution of Eating broke numerous records for
      museum attendance, highlighting the public's appetite for public health. During
      its 10-month run at the Yale Peabody Museum of Natural History, more than 120 000
      visitors attended Big Food, including 25 000 students through the museum's public
      education program, an increase of 30% more than the average student attendance in
      the past decade. Big Food cost approximately $100 000 to build, comprising
      printed panels and objects, installation displays (e.g., custom-built cases to
      house such objects as sugar-sweetened beverages and healthy and diseased organs),
      temporary walls, video monitors, food products, and more. At less than $1 per
      visitor, this provided extraordinary public health value. 

PMID- 24134357
TI  - Missed opportunities for hepatitis C testing and other opportunistic health care.

PMID- 24134358
TI  - "Screening" for prostate cancer in New York's skid row: history and implications.
AB  - The Bowery series, open perineal biopsies performed on more than 1200 alcoholic
      men recruited from homeless shelters in New York City's Bowery section, began in
      1951 and persisted for more than a decade. If frozen sections revealed prostate
      cancer, men typically underwent radical perineal prostatectomy, orchiectomy, and
      diethylstilbestrol treatment. This poorly informed, vulnerable population was
      subjected to health risks that investigators knew others would not accept.
      Although the knowledge produced had little impact on practice, the Bowery
      practices foreshadowed and have troubling continuities with later developments.
      Currently, more than a million American men each year undergo prostatic biopsies.
      But the efficacy of prostate-specific antigen screening and the treatment that
      typically follows has never been established. The Bowery series and subsequent
      developments are part of one continuous story of how medical and lay people came
      to believe in the efficacy of population screening followed by aggressive
      treatment without solid supporting scientific evidence. 

PMID- 24134359
TI  - Suicide mortality following nursing home discharge in the Department of Veterans
      Affairs health system.
AB  - OBJECTIVES: We assessed suicide rates up to 6 months following discharge from US
      Department of Veterans Affairs (VA) nursing homes. METHODS: In VA Minimum Data
      Set (MDS) records, we identified 281 066 live discharges from the 137 VA nursing
      homes during fiscal years 2002 to 2008. We used MDS and administrative data to
      assess resident age, gender, behaviors, pain, and indications of psychoses,
      bipolar disorder, dementia, and depression. We identified vital status and
      suicide mortality within 6 months of discharge through National Death Index
      searches. RESULTS: Suicide rates within 6 months of discharge were 88.0 per 100
      000 person-years for men and 89.4 overall. Standardized mortality ratios relative
      to age- and gender-matched individuals in the VA patient population were 2.3 for
      men (95% confidence interval [CI] = 1.9, 2.8) and 2.4 overall (95% CI = 2.0,
      2.9). In multivariable proportional hazards regression analyses, resident
      characteristics, diagnoses, behaviors, and pain were not significantly associated
      with suicide risk. CONCLUSIONS: Suicide risk was elevated following nursing home
      discharge. This underscores the importance of ongoing VA efforts to enhance
      discharge planning and timely postdischarge follow-up.

PMID- 24134360
TI  - Strengthening the network of mentored, underrepresented minority scientists and
      leaders to reduce HIV-related health disparities.
AB  - OBJECTIVES: We reviewed data for the Minority HIV/AIDS Research Initiative
      (MARI), which was established in 2003 to support underrepresented minority
      scientists performing HIV prevention research in highly affected communities.
      METHODS: MARI was established at the Centers for Disease Prevention and Control
      as a program of competitively awarded, mentored grants for early career
      researchers conducting HIV prevention research in highly affected racial/ethnic
      and sexual minority communities. We have described progress from 2003 to 2013.
      RESULTS: To date, MARI has mentored 27 scientist leaders using low-cost
      strategies to enhance the development of effective HIV prevention interventions.
      These scientists have (1) developed research programs in disproportionately
      affected communities of color, (2) produced first-authored peer-reviewed
      scientific and programmatic products (including articles and community-level
      interventions), and (3) obtained larger, subsequent funding awards for research
      and programmatic work related to HIV prevention and health disparities work.
      CONCLUSIONS: The MARI program demonstrates how to effectively engage minority
      scientists to conduct HIV prevention research and reduce racial/ethnic
      investigator disparities and serves as a model for programs to reduce disparities
      in other public health areas in which communities of color are disproportionately
      affected.

PMID- 24134361
TI  - Effects of the minimum legal drinking age on alcohol-related health service use
      in hospital settings in Ontario: a regression-discontinuity approach.
AB  - OBJECTIVES: We assessed the impact of the minimum legal drinking age (MLDA) on
      hospital-based treatment for alcohol-related conditions or events in Ontario,
      Canada. METHODS: We conducted regression-discontinuity analyses to examine MLDA
      effects with respect to diagnosed alcohol-related conditions. Data were derived
      from administrative records detailing inpatient and emergency department events
      in Ontario from April 2002 to March 2007. RESULTS: Relative to youths slightly
      younger than the MLDA, youths just older than the MLDA exhibited increases in
      inpatient and emergency department events associated with alcohol-use disorders
      (10.8%; P = .048), assaults (7.9%; P < .001), and suicides related to alcohol
      (51.8%; P = .01). Among young men who had recently crossed the MLDA threshold,
      there was a 2.0% increase (P = .01) in hospitalizations for injuries.
      CONCLUSIONS: Young adults gaining legal access to alcohol incur increases in
      hospital-based care for a range of serious alcohol-related conditions. Our
      regression-discontinuity approach can be used in future studies to assess the
      effects of the MLDA across different settings, and our estimates can be used to
      inform cost-benefit analyses across MLDA scenarios.

PMID- 24134362
TI  - Revisiting the role of the urban environment in substance use: the case of
      analgesic overdose fatalities.
AB  - OBJECTIVES: We examined whether neighborhood social characteristics (income
      distribution and family fragmentation) and physical characteristics (clean
      sidewalks and dilapidated housing) were associated with the risk of fatalities
      caused by analgesic overdose. METHODS: In a case-control study, we compared 447
      unintentional analgesic opioid overdose fatalities (cases) with 3436
      unintentional nonoverdose fatalities and 2530 heroin overdose fatalities
      (controls) occurring in 59 New York City neighborhoods between 2000 and 2006.
      RESULTS: Analgesic overdose fatalities were less likely than nonoverdose
      unintentional fatalities to have occurred in higher-income neighborhoods (odds
      ratio [OR] = 0.82; 95% confidence interval [CI] = 0.70, 0.96) and more likely to
      have occurred in fragmented neighborhoods (OR = 1.35; 95% CI = 1.05, 1.72). They
      were more likely than heroin overdose fatalities to have occurred in higher
      income (OR = 1.31; 95% CI = 1.12, 1.54) and less fragmented (OR = 0.71; 95% CI =
      0.55, 0.92) neighborhoods. CONCLUSIONS: Analgesic overdose fatalities exhibit
      spatial patterns that are distinct from those of heroin and nonoverdose
      unintentional fatalities. Whereas analgesic fatalities typically occur in lower
      income, more fragmented neighborhoods than nonoverdose fatalities, they tend to
      occur in higher-income, less unequal, and less fragmented neighborhoods than
      heroin fatalities.

PMID- 24134363
TI  - Ethical issues in conducting research with deaf populations.
AB  - Deaf American Sign Language (ASL) users represent a small population at risk for
      marginalization from research and surveillance activities resulting from
      cultural, language, and ethical challenges. The Deaf community's view of deafness
      as a cultural identity, rather than a disability, contradicts the medical
      community's perception of deafness as a disease or deficiency in need of
      correction or elimination. These differences continue to have significant
      cultural and social implications within the Deaf community, resulting in mistrust
      of research opportunities. Two particularly contentious ethical topics for the
      Deaf community are the absence of community representation in genetic research
      and the lack of accessible informed consents and research materials. This article
      outlines a series of innovative strategies and solutions to these issues,
      including the importance of community representation and collaboration with
      researchers studying deaf populations. 

PMID- 24134364
TI  - Effects of early dental office visits on dental caries experience.
AB  - OBJECTIVES: We determined the association between timing of a first dentist
      office visit before age 5 years and dental disease in kindergarten. METHODS: We
      used North Carolina Medicaid claims (1999-2006) linked to state oral health
      surveillance data to compare caries experience for kindergarten students (2005
      2006) who had a visit before age 60 months (n=11,394) to derive overall exposure
      effects from a zero-inflated negative binomial regression model. We repeated the
      analysis separately for children who had preventive and tertiary visits. RESULTS:
      Children who had a visit at age 37 to 48 and 49 to 60 months had significantly
      less disease than children with a visit by age 24 months (incidence rate ratio
      [IRR]=0.88; 95% confidence interval [CI]=0.81, 0.95; IRR=0.75; 95% CI=0.69, 0.82,
      respectively). Disease status did not differ between children who had a tertiary
      visit by age 24 months and other children. CONCLUSIONS: Medicaid-enrolled
      children in our study followed an urgent care type of utilization, and access to
      dental care was limited. Children at high risk for dental disease should be given
      priority for a preventive dental visit before age 3 years.

PMID- 24134365
TI  - Racial/ethnic disparities in antiretroviral treatment among HIV-infected pregnant
      Medicaid enrollees, 2005-2007.
AB  - OBJECTIVES: We examined racial/ethnic differences in prenatal antiretroviral
      (ARV) treatment among 3259 HIV-infected pregnant Medicaid enrollees. METHODS: We
      analyzed 2005-2007 Medicaid claims data from 14 southern states, comparing rates
      of not receiving ARVs and suboptimal versus optimal ARV therapy. RESULTS: More
      than one third (37.3%) had zero claims for ARV drugs. Three quarters (73.4%) of
      346 Hispanic women received no prenatal ARVs. After we adjusted for covariates,
      Hispanic women had 3.89 (95% confidence interval = 2.58, 5.87) times the risk of
      not receiving ARVs compared with Whites. Hispanic women often had only 1 or 2
      months of Medicaid eligibility, perhaps associated with barriers for immigrants.
      Less than 3 months of eligibility was strongly associated with nontreatment
      (adjusted odds ratio = 29.0; 95% confidence interval = 13.4, 62.7). CONCLUSIONS:
      Optimal HIV treatment rates in pregnancy are a public health priority, especially
      for preventing transmission to infants. Medicaid has the surveillance and drug
      coverage to ensure that all HIV-infected pregnant women are offered treatment.
      States that offer emergency Medicaid coverage for only delivery services to
      pregnant immigrants are missing an opportunity to screen, diagnose, and treat
      pregnant women with HIV, and to prevent HIV in children.

PMID- 24134366
TI  - 25-Hydroxyvitamin D in the range of 20 to 100 ng/mL and incidence of kidney
      stones.
AB  - OBJECTIVES: Increasing 25-hydroxyvitamin D serum levels can prevent a wide range
      of diseases. There is a concern about increasing kidney stone risk with vitamin D
      supplementation. We used GrassrootsHealth data to examine the relationship
      between vitamin D status and kidney stone incidence. METHODS: The study included
      2012 participants followed prospectively for a median of 19 months. Thirteen
      individuals self-reported kidney stones during the study period. Multivariate
      logistic regression was applied to assess the association between vitamin D
      status and kidney stones. RESULTS: We found no statistically significant
      association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body
      mass index was significantly associated with kidney stone risk (odds ratio = 3.5;
      95% confidence interval = 1.1, 11.3). CONCLUSIONS: We concluded that a serum 25
      hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant
      association with kidney stone incidence.

PMID- 24134367
TI  - Comparative effectiveness of a faith-based HIV intervention for African American
      women: importance of enhancing religious social capital.
AB  - OBJECTIVES: We assessed the effectiveness of P4 for Women, a faith-based HIV
      intervention. METHODS: We used a 2-arm comparative effectiveness trial involving
      134 African American women aged 18 to 34 years to compare the effectiveness of
      the Centers for Disease Control and Prevention-defined evidence-based Sisters
      Informing Sisters about Topics on AIDS (SISTA) HIV intervention with P4 for
      Women, an adapted faith-based version of SISTA. Participants were recruited from
      a large black church in Atlanta, Georgia, and completed assessments at baseline
      and follow-up. RESULTS: Both SISTA and P4 for Women had statistically significant
      effects on this study's primary outcome-consistent condom use in the past 90 days
      as well as other sexual behaviors. However, P4 for Women also had statistically
      significant effects on the number of weeks women were abstinent, on all
      psychosocial mediators, and most noteworthy, on all measures of religious social
      capital. Results were achieved by enhancing structural social capital through
      ministry participation, religious values and norms, linking trust and by reducing
      negative religious coping. High intervention attendance may indicate the
      feasibility of conducting faith-based HIV prevention research for African
      American women. CONCLUSIONS: P4 for Women enhanced abstinence and safer sex
      practices as well as religious social capital, and was more acceptable than
      SISTA. Such efforts may assist faith leaders in responding to the HIV epidemic in
      African American women.

PMID- 24134369
TI  - George Wolff (1886-1952): spreading the legacy of Alfred Grotjahn to the United
      States.

PMID- 24134368
TI  - Moving forward: breaking the cycle of mistrust between American Indians and
      researchers.
AB  - American Indians (AIs) have some of the poorest documented health outcomes of any
      racial/ethnic group. Research plays a vital role in addressing these health
      disparities. Historical and recent instances of unethical research, specifically
      the Havasupai diabetes project, have generated mistrust in AI communities. To
      address the concerns about unethical research held by some AIs in the Heartland
      (Midwest), the Center for American Indian Community Health (CAICH) has launched a
      series of efforts to inform AIs about research participants' rights. CAICH
      educates health researchers about the importance of learning and respecting a
      community's history, culture, values, and wishes when engaging in research with
      that community. Through community-based participatory research, CAICH is also
      empowering AIs to assert their rights as research participants. 

PMID- 24134370
TI  - First, do no harm: the US sexually transmitted disease experiments in Guatemala.
AB  - Beginning in 1946, the United States government immorally and unethically-and,
      arguably, illegally-engaged in research experiments in which more than 5000
      uninformed and unconsenting Guatemalan people were intentionally infected with
      bacteria that cause sexually transmitted diseases. Many have been left untreated
      to the present day. Although US President Barack Obama apologized in 2010, and
      although the US Presidential Commission for the Study of Bioethical Issues found
      the Guatemalan experiments morally wrong, little if anything has been done to
      compensate the victims and their families. We explore the backdrop for this
      unethical medical research and violation of human rights and call for steps the
      United States should take to provide relief and compensation to Guatemala and its
      people. 

PMID- 24134371
TI  - Building trust for engagement of minorities in human subjects research: is the
      glass half full, half empty, or the wrong size?

PMID- 24134372
TI  - Research ethics and indigenous communities.
AB  - Institutional review boards (IRBs) function to regulate research for the
      protection of human participants. We share lessons learned from the development
      of an intertribal IRB in the Rocky Mountain/Great Plains Tribal region of the
      United States. We describe the process through which a consortium of Tribes
      collaboratively developed an intertribal board to promote community-level
      protection and participation in the research process. In addition, we examine the
      challenges of research regulation from a Tribal perspective and explore the
      future of Tribally regulated research that honors indigenous knowledge and
      promotes community accountability and transparency. We offer recommendations for
      researchers, funding agencies, and Tribal communities to consider in the review
      and regulation of research. 

PMID- 24134373
TI  - Katz et al. respond.

PMID- 24134374
TI  - Katz et al. respond.

PMID- 24134375
TI  - Rethinking the vulnerability of minority populations in research.
AB  - The Belmont Report, produced in 1979 by a United States government commission,
      includes minority populations among its list of vulnerable research participants.
      In this article, we consider some previous attempts to understand the
      vulnerability of minorities in research, and then provide our own account. First
      we examine the question of the representation of minorities in research. Then we
      argue that the best understanding of minorities, vulnerability, and research will
      begin with a broad understanding of the risk of individual members of minority
      groups to poor health outcomes. We offer a typology of vulnerability to help with
      this task. Finally, we show how researchers should be guided by this broad
      analysis in the design and execution of their research. 

PMID- 24134376
TI  - Launching native health leaders: reducing mistrust of research through student
      peer mentorship.
AB  - OBJECTIVES: We assessed the impact of Launching Native Health Leaders (LNHL), a
      peer-mentoring and networking program that introduced American Indian/Alaska
      Native (AI/AN) undergraduates to health and research careers and concepts of
      community-based participatory research (CBPR). METHODS: We conducted 15
      interviews and 1 focus group with students who had attended 1 or more LNHL
      meetings, which took place during 9 professional health research conferences in
      2006 to 2009. We completed data collection in 2010, within 1 to 4 years of LNHL
      participant engagement in program activities. RESULTS: Participants described
      identity and cultural challenges they encountered in academic institutions and
      how their views shifted from perceiving research as an enterprise conducted by
      community outsiders who were not to be trusted toward an understanding of CBPR as
      contributing to AI/AN health. CONCLUSIONS: LNHL provided a safe environment for
      AI/AN students to openly explore their place in the health and research arenas.
      Programs such as LNHL support AI/AN student development as leaders in building
      trust for academic-tribal partnerships.

PMID- 24134377
TI  - Migrant home attendants: regulation and practice in 7 countries.
AB  - We compared regulation and working and living conditions of foreign home
      attendants in 7 countries (Canada, Germany, Israel, Singapore, Spain, United
      Kingdom, United States). We conducted a literature search in the PSYCinfo,
      MEDLINE, and Google Scholar databases for 2002 to 2012. We found substantial
      between-country differences in the legal status of migrant caregivers and
      regulations regarding working and living conditions and drew 3 conclusions.
      Improving regulations will likely improve not only the well-being of foreign home
      attendants but also the care they provide. Countries in which many foreign home
      attendants work without specific legal entry programs should rethink their
      policies. Finally, requiring an employer's recommendation to obtain permanent
      residency may constrain foreign workers from registering complaints or leaving
      suboptimal employment situations. 

PMID- 24134378
TI  - The unique impact of abolition of Jim Crow laws on reducing inequities in infant
      death rates and implications for choice of comparison groups in analyzing
      societal determinants of health.
AB  - OBJECTIVES: We explored associations between the abolition of Jim Crow laws
      (i.e., state laws legalizing racial discrimination overturned by the 1964 US
      Civil Rights Act) and birth cohort trends in infant death rates. METHODS: We
      analyzed 1959 to 2006 US Black and White infant death rates within and across
      sets of states (polities) with and without Jim Crow laws. RESULTS: Between 1965
      and 1969, a unique convergence of Black infant death rates occurred across
      polities; in 1960 to 1964, the Black infant death rate was 1.19 times higher (95%
      confidence interval [CI] = 1.18, 1.20) in the Jim Crow polity than in the non-Jim
      Crow polity, whereas in 1970 to 1974 the rate ratio shrank to and remained at
      approximately 1 (with the 95% CI including 1) until 2000, when it rose to 1.10
      (95% CI = 1.08, 1.12). No such convergence occurred for Black-White differences
      in infant death rates or for White infants. CONCLUSIONS: Our results suggest that
      abolition of Jim Crow laws affected US Black infant death rates and that valid
      analysis of societal determinants of health requires appropriate comparison
      groups.

PMID- 24134379
TI  - Social cohesion and mortality: a survival analysis of older adults in Japan.
AB  - OBJECTIVES: We examined the association between social cohesion and mortality in
      a sample of older adults in Japan. METHODS: Data were derived from a cohort study
      of elderly individuals (65-84 years) in Shizuoka Prefecture; 14 001 participants
      were enrolled at baseline (1999) and followed up in 2002, 2006, and 2009. Among
      the 11 092 participants for whom we had complete data, 1427 had died during
      follow-up. We examined the association between social cohesion (assessed at both
      the community and individual levels) and subsequent mortality after control for
      baseline and time-varying covariates. We used clustered proportional hazard
      regression models to estimate hazard ratios (HRs) and confidence intervals (CIs).
      RESULTS: After control for individual characteristics, individual perceptions of
      community cohesion were associated with a reduced risk of all-cause mortality (HR
      = 0.78; 95% CI = 0.73, 0.84) as well as mortality from cardiovascular disease (HR
      = 0.75; 95% CI = 0.67, 0.84), pulmonary disease (HR = 0.66; 95% CI = 0.58, 0.75),
      and all other causes (HR = 0.76; 95% CI = 0.66, 0.89). However, no statistically
      significant relationship was found between community cohesion and mortality risk.
      CONCLUSIONS: Among the elderly in Japan, more positive individual perceptions of
      community cohesion are associated with reduced risks of all-cause and cause
      specific mortality.

PMID- 24134380
TI  - Paradigm shifts in disability and health: toward more ethical public health
      research.
AB  - Disability is often considered a health outcome disproportionately experienced by
      minority groups. It is also possible to view people with disabilities as a
      minority group that itself experiences health disparities. Calls to reduce these
      disparities necessitate the inclusion of people with developmental disabilities
      in research, although resulting ethical issues can thwart scientific progress.
      Using disability rights principles can help address ethical challenges and
      promote safe, respectful public health research. Examples include applying human
      rights frameworks, providing accommodations, attending to power, countering
      legacies of deficits-based models of disability, and transforming access to
      science more broadly. Collectively, these strategies can encourage broader
      engagement in safe, respectful, inclusive public health research aimed at
      promoting the health and well-being of people with developmental disabilities. 

PMID- 24134381
TI  - Creating research capacity through a tribally based institutional review board.
AB  - Tribal groups work tirelessly to maintain sovereignty rights, preserving and
      upholding tribal authority and protection over their land, people, businesses,
      and health. Moreover, the conduct of health science research by outsiders has had
      its share of an unethical, misguided, and abusive past. Tribally based
      institutional review boards (IRBs) are addressing these issues in an effort to
      control new health science research, set their own research agenda, and protect
      their people in the same spirit as has been accomplished through the perpetuation
      of sovereignty rights. We describe the success of a tribally based IRB at
      creating new capacity for health research and enhanced levels of trust, including
      bidirectional cultural education between academic researchers and tribal IRB
      committee members. 

PMID- 24134382
TI  - Seroprevalence of HIV, hepatitis B virus, and HCV among injection drug users in
      Connecticut: understanding infection and coinfection risks in a nonurban
      population.
AB  - OBJECTIVES: We examined HIV, hepatitis B virus (HBV), and HCV seroprevalence in
      an interim analysis and the potential risk factors associated with these
      infections among injection drug users (IDUs) residing in nonurban communities of
      southwestern Connecticut. METHODS: We recruited and interviewed active adult IDUs
      about their injection-associated risk and conducted serological tests for HIV,
      HBV, and HCV. Regression analyses were performed to identify risk factors for
      infection and coinfection. RESULTS: Among 446 participants, 51.6% carried at
      least 1 infection, and 16.3% were coinfected. Infection risk was associated with
      longer duration of injection use, overdose, substance abuse treatment,
      depression, and involvement with the criminal justice system. Coinfection was
      associated with longer injection drug use, lower education, overdose, and
      criminal justice involvement. Multivariate models identified injection drug use
      duration, substance abuse treatment, and criminal justice involvement as the most
      significant predictors of infection; injection drug use duration and education
      were the most significant predictors of coinfection. CONCLUSIONS: Suburban IDUs
      are at significant risk for acquiring single and multiple viral infections.
      Effective harm reduction strategies are needed to reach users early. There might
      be roles for interventions in the treatment and justice systems in which IDUs
      interact.

PMID- 24134383
TI  - Refining the notion of maturing out: results from the national epidemiologic
      survey on alcohol and related conditions.
AB  - OBJECTIVES: Our aim was to determine if the decrease in drug use disorders with
      age is attributable to changes in persistence, as implied by the notion of
      maturing out. Also, we examined the association between role transitions and
      persistence, recurrence, and new onset of drug use disorders. METHODS: We
      performed secondary analysis of the 2 waves of the National Epidemiologic Survey
      on Alcohol and Related Conditions data (baseline assessment 2001-2002, follow-up
      conducted 2004-2005). We conducted logistic regressions and multinomial logistic
      regression to determine the effect of age on wave 2 diagnosis status, as well as
      the interaction between age and role transitions. RESULTS: Rates of persistence
      were stable over the life span, whereas rates of new onset and recurrence
      decreased with age. Changes in parenthood, marital, and employment status were
      associated with persistence, new onset, and recurrence. We found an interaction
      between marital status and age. CONCLUSIONS: Our findings challenge commonly held
      notions that the age-related decrease in drug use disorders is attributable to an
      increase in persistence, and that the effects of role transitions are stronger
      during young, compared with middle and older, adulthood.

PMID- 24134384
TI  - Redressing past wrongs: changing the common rule to increase minority voices in
      research.
AB  - Numerous diseases disproportionately affect African Americans across
      socioeconomic, age, gender, and geographic groups. Despite the need for research
      into these disparities, African Americans are often underrepresented in research.
      The Tuskegee Syphilis Study receives much of the blame for this problem, but
      other contributing factors have also been identified. To date, government
      policies seeking to increase African American participation have had limited
      success, and recently proposed changes to the Common Rule do not address this
      problem. Therefore, we have proposed 3 changes: treating racial minorities as
      vulnerable, requiring community consultation in minority research, and increasing
      minority representation on institutional review boards. Coupled with other
      efforts, these changes could help increase minority representation in researching
      health disparities. 

PMID- 24134385
TI  - We can have it all: improved surveillance outcomes and decreased personnel costs
      associated with electronic reportable disease surveillance, North Carolina, 2010.
AB  - OBJECTIVES: We assessed the timeliness, accuracy, and cost of a new electronic
      disease surveillance system at the local health department level. We describe
      practices associated with lower cost and better surveillance timeliness and
      accuracy. METHODS: Interviews conducted May through August 2010 with local health
      department (LHD) staff at a simple random sample of 30 of 100 North Carolina
      counties provided information on surveillance practices and costs; we used
      surveillance system data to calculate timeliness and accuracy. We identified LHDs
      with best timeliness and accuracy and used these categories to compare
      surveillance practices and costs. RESULTS: Local health departments in the top
      tertiles for surveillance timeliness and accuracy had a lower cost per case
      reported than LHDs with lower timeliness and accuracy ($71 and $124 per case
      reported, respectively; P = .03). Best surveillance practices fell into 2
      domains: efficient use of the electronic surveillance system and use of
      surveillance data for local evaluation and program management. CONCLUSIONS:
      Timely and accurate surveillance can be achieved in the setting of restricted
      funding experienced by many LHDs. Adopting best surveillance practices may
      improve both efficiency and public health outcomes.

PMID- 24134386
TI  - Crossing the chasm of mistrust: collaborating with immigrant populations through
      community organizations and academic partners.
AB  - As a community partner and an academic researcher, we experienced the direct and
      extended benefits of a relatively small-scale, community-engaged informed consent
      process that developed in an immigrant occupational health study, Assessing and
      Controlling Occupational Health Risks for Immigrant Populations in Somerville,
      Massachusetts. The practice of human participants research played a positive role
      in the community, and both community partners and researchers, as well as the
      larger academic community, reaped unexpected benefits during the five-year
      project (2005-2010), which continue into the present. Lessons learned from our
      experience may be helpful for wider application. 

PMID- 24134387
TI  - Lymph node-positive bladder cancer: surgical, pathologic, molecular and
      prognostic aspects.
AB  - The presence of lymphatic metastasis is associated with markedly worse prognosis
      in patients with bladder cancer, although surgical resection and chemotherapy can
      still provide long-term survival for selected patients. The prognostic
      stratification of patients with positive lymph nodes has been broadly discussed
      in the current literature and a more extensive pelvic lymph node dissection and
      thorough pathologic assessment has been advocated. It is clear that
      stratification using the tumor node metastasis staging system is insufficient to
      adequately discriminate prognosis between patients with different lymph node
      involvement. Lymph node density and extranodal extension have been extensively
      investigated and appear to influence the prognosis of these patients. Molecular
      markers have been developed to improve the diagnosis of micrometastatic disease,
      and new targeted therapies have shown promising preclinical results and are now
      being tested in different clinical scenarios. 

PMID- 24134388
TI  - Antimicrobial effects of coprisin on wounds infected with Staphylococcus aureus
      in rats.
AB  - Antimicrobial peptides (AMPs) are naturally produced antibiotics that play
      important roles in host defense mechanisms. These proteins are found in variety
      of animal and plant species. The antibiotic effects of AMPs are gaining attention
      for use in human medicine. In this study, the antimicrobial effects of coprisin,
      a novel AMP isolated from the dung beetle (Copris tripartitus), were evaluated.
      The peptide was used to treat rats with wounds infected with Staphylococcus
      aureus. Coprisin accelerated wound closure both grossly and microscopically
      compared with the untreated group. Additionally, treatment with this peptide
      decreased phosphorylated-Smad2/3 (p-Smad2/3) levels, a downstream factor of the
      transforming growth factor-beta signaling pathway which is believed to inhibit
      reepithelization, in the nucleus and cytoplasm of regenerating cells. Moreover,
      increased cell populations and angiogenesis were observed in lesions treated with
      coprisin, suggesting that this peptide promotes wound healing via its
      antimicrobial activity against S. aureus. Our results demonstrated that coprisin
      is a potential therapeutic agent that can possibly replace traditional
      antibiotics and overcome microbial resistance. 

PMID- 24134389
TI  - Residence place as a risk factor in different types of fatal car accidents.
AB  - The association between place of residence, population density, relief and type
      of event (collision or non-collision of the vehicle) has not been evaluated in
      developing countries. The main objective of this study is to determine the
      differential factors associated with the occurrence of deaths of collision and
      non-collision automobile users in Patagonia, Argentina. A multiple logistic
      regression analysis was performed using as the dependent variable death by car
      accident (collision or non-collision of the vehicle) and sex, age, place of
      residence of the victim, relief and population density as the independent
      variables. Collision fatalities were related to areas of high population density,
      while non-collision fatalities were related to areas of low population density,
      mountainous landscape and place of residence of the victims outside the
      Patagonian region. The results obtained in this study indicate the need to
      develop differential primary prevention policies by place of residence of car
      occupants, focusing on Patagonia non-resident drivers and by emphasising non
      collision accidents. 

PMID- 24134390
TI  - Using structural and evolutionary information to detect and correct
      pyrosequencing errors in noncoding RNAs.
AB  - The analysis of the sequence-structure relationship in RNA molecules is not only
      essential for evolutionary studies but also for concrete applications such as
      error-correction in next generation sequencing (NGS) technologies. The
      prohibitive sizes of the mutational and conformational landscapes, combined with
      the volume of data to process, require efficient algorithms to compute sequence
      structure properties. In this article, we address the correction of NGS errors by
      calculating which mutations most increase the likelihood of a sequence to a given
      structure and RNA family. We introduce RNApyro, an efficient, linear time and
      space inside-outside algorithm that computes exact mutational probabilities under
      secondary structure and evolutionary constraints given as a multiple sequence
      alignment with a consensus structure. We develop a scoring scheme combining
      classical stacking base-pair energies to novel isostericity scores and apply our
      techniques to correct pointwise errors in 5s and 16s rRNA sequences. Our results
      suggest that RNApyro is a promising algorithm to complement existing tools in the
      NGS error-correction pipeline.

PMID- 24134391
TI  - NP-MuScL: unsupervised global prediction of interaction networks from multiple
      data sources.
AB  - Inference of gene interaction networks from expression data usually focuses on
      either supervised or unsupervised edge prediction from a single data source.
      However, in many real world applications, multiple data sources, such as
      microarray and ISH (in situ hybridization) measurements of mRNA abundances, are
      available to offer multiview information about the same set of genes. We propose
      ISH to estimate a gene interaction network that is consistent with such multiple
      data sources, which are expected to reflect the same underlying relationships
      between the genes. NP-MuScL casts the network estimation problem as estimating
      the structure of a sparse undirected graphical model. We use the semiparametric
      Gaussian copula to model the distribution of the different data sources, with the
      different copulas sharing the same precision (i.e., inverse covariance) matrix,
      and we present an efficient algorithm to estimate such a model in the high
      dimensional scenario. Results are reported on synthetic data, where NP-MuScL
      outperforms baseline algorithms significantly, even in the presence of noisy data
      sources. Experiments are also run on two real-world scenarios: two yeast
      microarray datasets and three Drosophila embryonic gene expression datasets,
      where NP-MuScL predicts a higher number of known gene interactions than existing
      techniques.

PMID- 24134392
TI  - Boosting prediction performance of protein-protein interaction hot spots by using
      structural neighborhood properties.
AB  - Binding of one protein to another in a highly specific manner to form stable
      complexes is critical in most biological processes, yet the mechanisms involved
      in the interaction of proteins are not fully clear. The identification of hot
      spots, a small subset of binding interfaces that account for the majority of
      binding free energy, is becoming increasingly important in understanding the
      principles of protein interactions. Despite experiments like alanine scanning
      mutagenesis and a variety of computational methods that have been applied to this
      problem, comparative studies suggest that the development of accurate and
      reliable solutions is still in its infant stage. We developed PredHS (Prediction
      of Hot Spots), a computational method that can effectively identify hot spots on
      protein-binding interfaces by using 38 optimally chosen properties. The optimal
      combination of features was selected from a set of 324 novel structural
      neighborhood properties by a two-step feature selection method consisting of a
      random forest algorithm and a sequential backward elimination method. We
      evaluated the performance of PredHS using a benchmark of 265 alanine-mutated
      interface residues (Dataset I) and a trimmed subset (Dataset II) with 10-fold
      cross-validation. Compared with the state-of-the art approaches, PredHS achieves
      a significant improvement on the prediction quality, which stems from the new
      structural neighborhood properties, the novel way of feature generation, as well
      as the selection power of the proposed two-step method. We further validated the
      capability of our method by an independent test and obtained promising results.

PMID- 24134393
TI  - Towards the discovery of novel genetic component involved in stress resistance in
      Arabidopsis thaliana.
AB  - The exposure of plants to high concentrations of trace metallic elements such as
      copper involves a remodeling of the root system, characterized by a primary root
      growth inhibition and an increase in the lateral root density. These
      characteristics constitute easy and suitable markers for screening mutants
      altered in their response to copper excess. A forward genetic approach was
      undertaken in order to discover novel genetic factors involved in the response to
      copper excess. A Cu(2+) -sensitive mutant named copper modified resistance1
      (cmr1) was isolated and a causative mutation in the CMR1 gene was identified by
      using positional cloning and next-generation sequencing. CMR1 encodes a plant
      specific protein of unknown function. The analysis of the cmr1 mutant indicates
      that the CMR1 protein is required for optimal growth under normal conditions and
      has an essential role in the stress response. Impairment of the CMR1 activity
      alters root growth through aberrant activity of the root meristem, and modifies
      potassium concentration and hormonal balance (ethylene production and auxin
      accumulation). Our data support a putative role for CMR1 in cell division
      regulation and meristem maintenance. Research on the role of CMR1 will contribute
      to the understanding of the plasticity of plants in response to changing
      environments. 

PMID- 24134394
TI  - Ameliorating effects of aged garlic extracts against Abeta-induced neurotoxicity
      and cognitive impairment.
AB  - BACKGROUND: In vitro antioxidant activities and neuron-like PC12 cell protective
      effects of solvent fractions from aged garlic extracts were investigated to
      evaluate their anti-amnesic functions. Ethyl acetate fractions of aged garlic had
      higher total phenolics than other fractions. METHODS: Antioxidant activities of
      ethyl acetate fractions from aged garlic were examined using 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) and malondialdehyde
      (MDA) inhibitory effect using mouse whole brain homogenates. Levels of cellular
      oxidative stress as reactive oxygen species (ROS) accumulation were measured
      using 2',7'-dichlorofluorescein diacetate (DCF-DA). PC12 cell viability was
      investigated by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide
      (MTT) and lactate dehydtrogenase (LDH) assay. The learning and memory impairment
      in institute of cancer research (ICR) mice was induced by neurotoxic amyloid beta
      protein (Abeta) to investigate in vivo anti-amnesic effects of aged garlic
      extracts by using Y-maze and passive avoidance tests. RESULTS: We discovered that
      ethyl acetate fractions showed the highest ABTS radical scavenging activity and
      MDA inhibitory effect. Intracellular ROS accumulation resulting from Abeta
      treatment in PC12 cells was significantly reduced when ethyl acetate fractions
      were presented in the medium compare to PC12 cells which was only treated with
      Abeta only. Ethyl acetate fractions from aged garlic extracts showed protection
      against Abeta-induced neurotoxicity. Pre-administration with aged garlic extracts
      attenuated Abeta-induced learning and memory deficits in both in vivo tests.
      CONCLUSIONS: Our findings suggest that aged garlic extracts with antioxidant
      activities may improve cognitive impairment against Abeta-induced neuronal
      deficit, and possess a wide range of beneficial activities for neurodegenerative
      disorders, notably Alzheimer's disease (AD).

PMID- 24134395
TI  - Evaluation of subclinical left ventricular dysfunction in diabetic patients:
      longitudinal strain velocities and left ventricular dyssynchrony by two
      dimensional speckle tracking echocardiography study.
AB  - BACKGROUND: We evaluated left ventricular (LV) subclinical systolic dysfunction
      in diabetes mellitus patients using two-dimensional speckle tracking
      echocardiography (STE) for early detection of changes in LV longitudinal strain
      (ST) or synchronized contraction. METHODS: To determine ST and LV dyssynchrony,
      37 normal coronary and normotensive diabetes mellitus patients with LV ejection
      fraction >50% were enrolled and compared to 39 nondiabetic normal coronary and LV
      function subjects. The cases underwent standard conventional transthoracic
      echocardiography and tissue Doppler imaging (TDI) and STE. End-systolic ST and
      time-to-peak systolic strain (Ts) were measured in 18 LV segments. RESULTS:
      Conventional parameters were similar between diabetic and nondiabetic subjects.
      In diabetic patients, significant reduction in global and segmental ST adjusted
      for age and body mass index, independently correlated with early diastolic
      velocity at the septal mitral valve annulus by TDI (P = 0.001), ratio of
      transmitral early and late diastolic velocities (P < 0.001), relative wall
      thickness (P = 0.014), glycosylated hemoglobin (P < 0.001), and fasting blood
      sugar (P < 0.001). These correlations were not found in the nondiabetic patients.
      After adjustment, presence of diabetes mellitus remained an independent correlate
      of reduced LV global longitudinal ST (R = 0.688, P = 0.003). Delay of Ts between
      the anteroseptal and posterior walls and all the LV segments was markedly higher
      in the diabetic group regardless of diastolic dysfunction. CONCLUSION: In
      diabetic patients with normal coronary and ejection fraction, segmental and
      global end-systolic longitudinal ST decreased and differences between Ts among LV
      segments increased irrespective of diastolic dysfunction at early stage. These
      results suggest that there might be early detectable changes in systolic function
      in the natural course of diabetes mellitus by STE study.

PMID- 24134396
TI  - Registering medicines for low-income countries: how suitable are the stringent
      review procedures of the World Health Organisation, the US Food and Drug
      Administration and the European Medicines Agency?
AB  - New medicines are registered after a resource-demanding process. Unfortunately,
      in low-income countries (LICs), demand outweighs resources. To facilitate
      registration in LICs, stringent review procedures of the European Medicines
      Agency (EMA Article-58), Food and Drug Administration (FDA PEPFAR-linked review)
      and WHO Prequalification programme have been established. Only the PEPFAR-linked
      review gives approval, while the others make recommendations for approval. This
      study assessed the performance and discussed the challenges of these three
      stringent review procedures. Data from WHO, FDA, EMA, Medline and Internet were
      analysed. Over 60% of medicines reviewed by stringent review procedures are
      manufactured in India. Until 2012, WHO prequalified 400 medicines (211 vaccines,
      130 antiretrovirals, 29 tuberculostatics, 15 antimalarials and 15 others). PEPFAR
      linked review approved 156 antiretrovirals, while EMA Article 58 recommended
      approval of 3 antiretrovirals, 1 vaccine and 1 antimalarial. WHO Prequalification
      and PEPFAR-linked review are free of charge and as a result have accelerated
      access to antiretrovirals. They both built capacity in sub-Saharan Africa,
      although WHO prequalification relies technically on stringent regulatory
      authorities and financially on donors. Article-58 offers the largest disease
      coverage and strongest technical capacities, is costly and involves fewer LICs.
      To meet the high demand for quality medicines in LICs, these stringent review
      procedures need to enlarge their disease coverage. To improve registration, EMA
      Article 58 should actively involve LICs. Furthermore, LIC regulatory activities
      must not be fully resigned to stringent review procedure.

PMID- 24134397
TI  - Integrating the 'genomic mosaic' view of species into studies of biotic
      interactions: a comment on Bernhardsson et al. ().
AB  - The co-occurrence of geographical structure in herbivore communities, metabolomes
      and defence genes in forest trees has been analysed in the context of
      'geographical mosaics' of coevolution. A deeper understanding of these important
      issues will require full integration of a 'genomic mosaic' view of species into
      community ecology. 

PMID- 24134398
TI  - Night work and the reproductive health of women: an integrated literature review.
AB  - INTRODUCTION: The aim of this review was to synthesize current evidence on the
      effects of night work on the major stages of women's reproductive health,
      specifically the menstrual cycle, fertility, pregnancy, and menopause. Current
      understanding suggests that night work (work that causes disruption of a worker's
      circadian [day/night] rhythms) adversely affects workers' health and well-being.
      A complex relationship exists between circadian rhythms and reproductive
      hormones, and this may potentially increase the vulnerability of women to the
      detrimental effect of night work, including during menopause. METHODS: A
      systematic search was conducted (March-May 2011) via CINAHL, MEDLINE,
      Sociological Abstracts, and Business Source Premier for primary research studies
      written in English using the key words "shift-work" and "female/women." Findings
      of identified articles were themed to pregnancy, fertility, aspects of menstrual
      cycles, and menopause. RESULTS: Twenty articles were identified, (13 articles
      concerning pregnancy, 3 addressing fertility, and 4 addressing aspects of the
      menstrual cycle) but no studies addressing menopause were located. All identified
      articles demonstrated problematic approaches to the determination of night-work
      exposure. DISCUSSION: Evidence of the impact of night work on female reproductive
      health as presented in the current literature is inconclusive. Moreover,
      available evidence needs to be interpreted with caution, given the various
      limitations and inconsistencies among the studies in the measurement of night
      work exposure and shift-work patterns. Studies that focus specifically on night
      work are needed to facilitate an understanding of the impact of circadian
      disruption on the reproductive health of women undertaking night work.

PMID- 24134399
TI  - Water- and humidity-enhanced UV detector by using p-type La-doped ZnO nanowires
      on flexible polyimide substrate.
AB  - High-density La-doped ZnO nanowires (NWs) were grown hydrothermally on flexible
      polyimide substrate. The length and diameter of the NWs were around 860 nm and 80
      160 nm, respectively. All XRD peaks of the La-doped sample shift to a larger
      angle. The strong PL peak of the La-doped sample is 380 nm, which is close to the
      3.3 eV ZnO bandgap. That PL dominated indicates that the La-doped sample has a
      great amount of oxygen vacancies. The lattice constants ~0.514 nm of the ZnO:La
      NW were smaller when measured by HR-TEM. The EDX spectrum determined that the La
      doped sample contains approximately 1.27 at % La. The La-doped sample was found
      to be p-type by Hall Effect measurement. The dark current of the p-ZnO:La NWs
      decreased with increased relative humidity (RH), while the photocurrent of the p
      ZnO:La nanowires increased with increased RH. The higher RH environment was
      improved that UV response performance. Based on the highest 98% RH, the
      photocurrent/dark current ratio was around 47.73. The UV response of water drops
      on the p-ZnO:La NWs was around 2 orders compared to 40% RH. In a water
      environment, the photocurrent/dark current ratio of p-ZnO:La NWs was 212.1, which
      is the maximum UV response.

PMID- 24134400
TI  - A nationwide population-based retrospective cohort study: increased risk of acute
      coronary syndrome in patients with ankylosing spondylitis.
AB  - OBJECTIVES: To compare the risk of acute coronary syndrome (ACS) between patients
      with and without ankylosing spondylitis (AS). METHOD: This retrospective cohort
      study identified all patients with AS aged >= 18 years newly diagnosed from 2000
      to 2009, registered in the National Health Insurance Research Database (NHIRD) in
      Taiwan. The non-AS cohort consisted of fourfold randomly selected control
      patients free of AS, frequency matched by age, sex, and diagnosis year. The
      incidence of ACS was determined for both AS and non-AS cohorts. RESULTS: We
      selected 6262 patients with AS and 25 048 patients without AS. The patients with
      AS were more prevalent than those without, with co-morbidities of hypertension,
      diabetes mellitus (DM), hyperlipidaemia, stroke, and peripheral vascular
      diseases. The overall incidence rate of ACS was higher in the AS cohort than in
      the non-AS cohort (4.4 vs. 2.9 per 1000 person-years), with an adjusted hazard
      ratio (aHR) of 1.36 [95% confidence interval (CI) 1.16-1.59]. AS patients with co
      morbidities of hypertension, DM, and cancer had an aHR of 7.74 for ACS, compared
      to those without these co-morbidities. CONCLUSIONS: AS patients are at higher
      risk of ACS compared with non-AS subjects. Management of CV risk factors should
      be taken into account for the treatment of patients with AS, especially for
      patients with co-morbidities of hypertension, DM, and cancer.

PMID- 24134401
TI  - Asexuality: few facts, many questions.
AB  - Although there has been increasing interest in asexuality during the past decade,
      still little is known on this topic. To define asexuality, three different
      approaches have been proposed: a definition that is based on sexual behavior, one
      on sexual desire/sexual attraction, one on self-identification, and one on a
      combination of these. Depending on the definition used, reported prevalence rates
      range from 0.6% to 5.5%. In this article, the authors present characteristics of
      asexuality and review biological, psychological, and sociodemographic factors
      associated with asexuality. Given the suggestion of existing overlap with
      hypoactive sexual desire disorder, special attention is paid to similarities and
      differences between this condition and asexuality. It is further noted that
      theoretical models to understand (the etiology) of asexuality are underdeveloped.

PMID- 24134402
TI  - Serum vitamin D level and disease activity in patients with recent onset
      rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid Arthritis (RA) is one of the most prevalent autoimmune
      diseases. Due to the significance of the relationship between serum vitamin D
      levels and autoimmune diseases, this study aimed to determine the relationship
      between serum vitamin D level and the severity of disease activity in patients
      with newly diagnosed RA. METHOD: This cross-sectional study was conducted on 66
      patients meeting the American College of Rheumatology - European League Against
      Rheumatism classification criteria for RA. It was performed in 2012 using simple
      sampling. The disease activity was measured based on Disease Activity Score of 28
      joints - erythrocyte sedimentation rate (DAS28-ESR) and serum 25-OH vitamin D
      (25(OH)D) levels using the chemiluminescent immunoassay method. In addition, the
      levels of ESR and C-reactive protein (CRP), the duration of morning stiffness,
      and the number of joints with tenderness and swollen were calculated as well. The
      data were analyzed using the Pearson correlation coefficient. RESULTS: In this
      study, 10 patients were male (15.2%) and 56 were female (84.8%). The average age
      of the participants was 45.2 +/- 15.3 years. The average level of 25(OH)D in the
      patients' serum was 30.5 +/- 28.9 ng/mL and the mean DAS28-ESR was 5.6 +/- 1.1.
      The correlation coefficient showed that there was an inverse relationship between
      25(OH)D and DAS28-ESR, the number of tender and swollen joints, global patient
      assessment and duration of morning stiffness (P < 0.01). However, the average
      25(OH)D level was not related to ESR (P = 0.779) and CRP (P = 0.269). CONCLUSION:
      The results of this analysis indicated that patients with more active RA have a
      lower serum vitamin D level.

PMID- 24134403
TI  - Chiral hybrid inorganic-organic materials: synthesis, characterization, and
      application in stereoselective organocatalytic cycloadditions.
AB  - The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles,
      exploiting two different anchoring sites and two different linkers, is reported.
      Catalysts 1-4 were prepared starting from l-phenylalanine or l-tyrosine methyl
      esters and supporting the imidazolidinone onto silica by grafting protocols or
      azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully
      characterized by solid-state NMR, N2 physisorption, SEM, and TGA in order to
      provide structural assessments, including an evaluation of surface areas, pore
      dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder
      cycloadditions between cyclopentadiene and different aldehydes, affording results
      comparable to those obtained with the nonsupported catalyst (up to 91% yield and
      92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The
      catalysts were recovered from the reaction mixture by simple filtration or
      centrifugation. The most active catalyst was recycled two times with some loss of
      catalytic efficiency and a small erosion of ee. 

PMID- 24134404
TI  - Conformational preference and chiroptical response of carbohydrates D-ribose and
      2-deoxy-D-ribose in aqueous and solid phases.
AB  - This work targets the structural preferences of D-ribose and 2-deoxy-D-ribose in
      water solution and solid phase. A theoretical DFT (B3LYP and M06-2X) and MP2
      study has been undertaken considering the five possible configurations (open
      chain, alpha-furanose, beta-furanose, alpha-pyranose, and beta-pyranose) of these
      two carbohydrates with a comparison of the solvent treatment using only a
      continuum solvation model (PCM) and the PCM plus one explicit water molecule. In
      addition, experimental vibrational studies using both nonchiroptical (IR-Raman)
      and chiroptical (VCD) techniques have been carried out. The theoretical and
      experimental results show that alpha- and beta-pyranose forms are the dominant
      configurations for both compounds. Moreover, it has been found that 2-deoxy-D
      ribose presents a non-negligible percentage of open-chain forms in aqueous
      solution, while in solid phase this configuration is absent.

PMID- 24134405
TI  - Single dose recombinant erythropoietin versus moderate hypothermia for neonatal
      hypoxic ischemic encephalopathy in low resource settings.
AB  - OBJECTIVE: To determine the safety and efficacy of single dose systemic
      recombinant human erythropoietin (rEPO) in neonates with perinatal hypoxic
      Ischemic Encephalopathy (HIE), and its effect on serum brain-derived neurotrophic
      factor (BDNF) and neuron-specific enolase (NSE). METHODS: Forty-five full-term
      neonates; 30 with perinatal HIE and 15 controls were studied. HIE neonates were
      randomized into three intervention groups (first 6 h of life): 10 received single
      subcutaneous 1500 U/kg rEPO at day-1, 10 subjected to hypothermia for 72 h and 10
      received supportive care. BDNF and NSE measured during first 6 h and day 5
      postnatal. Daily Thompson's score, MRI brain and neuromuscular function scale for
      survivors at 3 months of age were done. RESULTS: Hypothermia group had best
      survival especially with stage-II Sarnat scale, followed by rEpo and supportive
      group. BDNF day-5 was significantly higher in each group compared to controls.
      MRI score and neuromuscular function score were non-significantly lower in the
      hypothermia group compared to rEPO. CONCLUSIONS: Therapeutic hypothermia was
      superior to single dose rEpo for neuro-protection in HIE especially in patients
      with stage-II Sarnat scale. Therapeutic effect of combined rEPO multiple dosing
      and modest hypothermia therapy should be studied.

PMID- 24134406
TI  - Aqueous solution synthesis of reduced graphene oxide-germanium nanoparticles and
      their electrical property testing.
AB  - Aqueous solution synthesis of reduced graphene oxide-germanium nanoparticles (RGO
      GeNPs) was developed using graphene oxide (GO) as stabilizer, which could be
      conducive to obtain better excellent electrical properties. The information about
      morphology and chemical composition of the nanomaterials were obtained by TEM,
      FTIR, EDS, and XRD measurements. Stable aqueous dispersibility of RGO-GeNPs was
      further improved by poly(sodium 4-styrenesulfonate) (PSS) to obtain amphiphilic
      polymer-coated RGO-GeNPs (PSS-RGO-GeNPs). A possible mechanism to interpret the
      formation of RGO-GeNPs was proposed. The as-synthesized RGO-GeNPs showed
      excellent battery performance when used as an anode material for Li ion
      batteries. The resulting nanocomposites exhibited high specific capacity and good
      cycling stability after 80 cycles. This study showed a facile strategy to
      synthetize graphene and Ge nanocomposites which can be a hopeful anode material
      with excellent electrical properties for lithium ion batteries. 

PMID- 24134407
TI  - Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV
      infected patient: a case report.
AB  - BACKGROUND: Sexually transmitted diseases and most notably syphilis-infections
      are rising amongst men who have sex with men. In HIV-co-infected patients, an
      accelerated clinical course of syphilis neurological involvement is known. CASE
      PRESENTATION: A 46 year old HIV-positive male patient came in to our emergency
      department in the late evening with acute fever, rapidly progressive cephalgia
      and photophobia. Palmar skin efflorescence was evocative of an active syphilis
      infection. A reactive Treponema pallidum particle agglutination (TPPA) assay with
      positive Treponema pallidum-specific IgG/IgM immunofluorescence as well as a
      highly reactive Veneral diseases research laboratory (VDRL) test confirmed the
      diagnosis. Liquor pleocytosis, liquor protein elevation and a highly positive
      VDRL test in cerebrospinal fluid (CSF) were interpreted in context of the
      clinical symptoms as neurosyphilitic manifestations within an early syphilis
      infection (stage II). Cranial nuclear magnetic resonance scans of the sella
      turcica, which were performed due to low thyroidea stimulation hormone (TSH) and
      thyroxin levels, showed signs of hypophysitis such as pituitary gland enlargement
      and inhomogeneous contrast enhancement. Advanced endocrine laboratory testing
      revealed hypopituitarism. Fourteen days of intravenous ceftriaxone treatment and
      levothyroxine- and hydrocortisone-substitution led to complete disappearance of
      all clinical symptoms. Two months later, nuclear magnetic resonance scan showed
      normal pituitary size and that the syphilis serology had normalized. CONCLUSION:
      We report to the best of our knowledge the first case of a HIV-positive patient
      with acute hypophysitis and hypopituarism due to early neurosyphilis infection.
      Ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to
      the disappearance of all clinical symptoms. We strongly recommend to exclude
      syphilis infection in every clinical situation unclear in HIV-patients,
      especially when additional risk factors are known.

PMID- 24134408
TI  - The effect of resin infiltration and oxidative pre-treatment on microshear bond
      strength of resin composite to hypomineralised enamel.
AB  - BACKGROUND: Reduced bond strengths of resin composites to hypomineralised enamel
      increase restorative failure. AIM: To investigate if the adhesion of resin
      composite to hypomineralised enamel can be improved by pre-treatments: resin
      infiltration, oxidative pre-treatment followed by a resin infiltration, or
      oxidative pre-treatment. DESIGN: Twenty-one enamel specimens in each of five
      Groups: 1) Normal enamel; 2) Hypomineralised enamel; 3) Hypomineralised enamel
      pre-treated with a resin infiltrant, (Icon((r))); 4) Hypomineralised enamel pre
      treated with 5.25% sodium hypochlorite then treatment with resin infiltrant; 5)
      Hypomineralised enamel pre-treated with 5.25% sodium hypochlorite. A resin
      composite rod was bonded to each specimen using ClearfilTM SE bond as the
      adhesive (hereafter termed 'routine bonding'), then subjected to microshear bond
      strength (MSBS) testing. RESULTS: Overall, the mean MSBS between the five groups
      differed significantly (P = 0.001). Pre-treatment of hypomineralised enamel with
      5.25% sodium hypochlorite with or without subsequent resin infiltration in Groups
      4 and 5 prior to routine bonding resulted in increased mean MSBS compared to
      Groups 2 and 3, with mean MSBS values not differing significantly when compared
      to routine bonding to normal enamel. CONCLUSION: Increased bond strength of resin
      composite to hypomineralised enamel was obtained by pre-treatment of
      hypomineralised enamel specimens with 5.25% sodium hypochlorite with or without
      subsequent resin infiltration.

PMID- 24134409
TI  - Interpretation of World Health Organization growth charts for assessing infant
      malnutrition: a randomised controlled trial.
AB  - AIMS: The study aims to assess the effects of switching from National Center for
      Health Statistics (NCHS) growth references to World Health Organization (WHO)
      growth standards on health-care workers' decisions about malnutrition in infants
      aged <6 months. METHODS: We conducted a single blind randomised crossover trial
      involving 78 health-care workers (doctors, clinical officers, health service
      assistants) in Southern Malawi. Participants were offered hypothetical clinical
      scenarios with the same infant plotted on NCHS-based weight-for-age charts and
      again on WHO-based charts. Additional scenarios compared growth charts with a
      single final weight against charts with the same final weight plus a preceding
      growth trend. Reported (i) level of concern, (ii) referral suggestions and (iii)
      feeding advice were elicited with a questionnaire. RESULTS: Even after adjusting
      for health-care worker type and experience, using WHO rather than NCHS charts
      increased: (i) concern: aOR 4.4 (95% CI 2.4-8.1); (ii) odds of referral: aOR 5.1
      (95% CI 2.4-10.8); and (iii) odds of feeding advice which would interrupt
      exclusive breastfeeding (aOR 2.4, 95% CI 1.2-4.9). A preceding steady growth
      trend line did not affect concern, referral or feeding advice. CONCLUSIONS:
      Health-care workers take insufficient account of linear growth trend, clinical
      and feeding status when interpreting a low weight-for-age plot. Because more
      infants <6 months fall below low centile lines on WHO growth charts, their use
      may increase inappropriate referrals and risks undermining already low rates of
      exclusive breastfeeding. To avoid their being misinterpreted in this way, WHO
      charts need accompanying guidelines and training materials that recognise and
      address this possible adverse effect.

PMID- 24134410
TI  - Validity and reliability of the French versions of the body shape questionnaire.
AB  - The validity of the 34-item and shortened versions of the Body Shape
      Questionnaire (BSQ) has been evaluated in various languages. To date, only the
      validity of the 34-item French BSQ scale has been tested in a nonclinical sample.
      This study assessed the reliability and validity of the 34-item French BSQ and 7
      shortened versions in clinical and nonclinical samples. The 34-item French BSQ
      was administered to 159 obese women with and without binge eating disorders and
      to 1,169 female undergraduate students. The results suggested that the BSQ-8B was
      the best French BSQ to use in nonclinical and clinical samples. 

PMID- 24134411
TI  - Characterization of mannose-binding lectin (MBL) variants by allele-specific
      sequencing of MBL2 and determination of serum MBL protein levels.
AB  - Mannose-binding lectin (MBL) is a major component of the lectin pathway of
      complement activation. High and low MBL levels have been associated with
      susceptibility and severity of a variety of infectious and autoimmune diseases.
      Several single-nucleotide polymorphisms (SNPs) in the promoter region and exon 1
      of the MBL2 gene are responsible for variations in serum MBL levels. We developed
      a sequence-based typing method for allele-specific MBL2 genotyping and measured
      serum MBL protein levels in 24 German blood donors. We identified the common MBL2
      haplotypes including five promoter polymorphisms in linkage with the Q allele and
      correlated serum MBL levels with the respective genotypes. The genotyping method
      presented here could provide a basis for confirmatory studies in larger cohorts. 

PMID- 24134412
TI  - Cutaneous T-cell lymphoma in patients with chronic lymphocytic leukemia: clinical
      characteristics, temporal relationships, and survival data in a series of 14
      patients at Mayo Clinic.
AB  - BACKGROUND: We examined the course of cutaneous T-cell lymphoma (CTCL), which has
      been associated with chronic lymphocytic leukemia (CLL) in patients with CLL.
      MATERIALS AND METHODS: A search was conducted of the master diagnosis index at
      our institution to identify patients with both CLL and CTCL from 1980 to 2010. A
      retrospective chart review was then conducted. RESULTS: Of the 14 patients with
      CTCL and CLL, eight had mycosis fungoides (MF; two with patch stage, two with
      plaque stage, two with tumor stage, and two with erythrodermic stage), four had
      Sezary syndrome, one had natural killer cell lymphoma involving the skin, and one
      had peripheral T-cell lymphoma involving the skin. Eight had concurrent
      diagnoses, five received a CLL diagnosis first, and one received a CTCL diagnosis
      first. Ten patients were deceased at the time of data abstraction due to unknown
      causes (n = 4), lymphoma (n = 2), pneumonia (n = 2), MF (n = 1), or respiratory
      failure (n = 1). Of the nine patients with concurrent or prior CTCL, seven were
      deceased, with a median time to death of 10.2 months (range, 6-89 months). Of the
      five patients with CLL prior to CTCL, three were deceased at 18, 27, and 47
      months, respectively, after the CTCL diagnosis. The median survival for the two
      groups was 12 and 47 months, respectively. CONCLUSIONS: Patients with CTCL
      concurrent with or prior to CLL have a worse overall survival than patients with
      CLL in whom CTCL later develops. Larger studies are needed.

PMID- 24134413
TI  - Use of safety management practices for improving project performance.
AB  - Although site safety has long been a key research topic in the construction
      field, there is a lack of literature studying safety management practices (SMPs).
      The current research, therefore, aims to test the effect of SMPs on project
      performance. An empirical study was conducted in Hong Kong and the data collected
      were analysed with multiple regression analysis. Results suggest that 3 of the 15
      SMPs, which were 'safety committee at project/site level', 'written safety
      policy', and 'safety training scheme' explained the variance in project
      performance significantly. Discussion about the impact of these three SMPs on
      construction was provided. Assuring safe construction should be an integral part
      of a construction project plan. 

PMID- 24134414
TI  - Prone position in acute respiratory distress syndrome. Rationale, indications,
      and limits.
AB  - In the prone position, computed tomography scan densities redistribute from
      dorsal to ventral as the dorsal region tends to reexpand while the ventral zone
      tends to collapse. Although gravitational influence is similar in both positions,
      dorsal recruitment usually prevails over ventral derecruitment, because of the
      need for the lung and its confining chest wall to conform to the same volume. The
      final result of proning is that the overall lung inflation is more homogeneous
      from dorsal to ventral than in the supine position, with more homogeneously
      distributed stress and strain. As the distribution of perfusion remains nearly
      constant in both postures, proning usually improves oxygenation. Animal
      experiments clearly show that prone positioning delays or prevents ventilation
      induced lung injury, likely due in large part to more homogeneously distributed
      stress and strain. Over the last 15 years, five major trials have been conducted
      to compare the prone and supine positions in acute respiratory distress syndrome,
      regarding survival advantage. The sequence of trials enrolled patients who were
      progressively more hypoxemic; exposure to the prone position was extended from 8
      to 17 hours/day, and lung-protective ventilation was more rigorously applied.
      Single-patient and meta-analyses drawing from the four major trials showed
      significant survival benefit in patients with PaO2/FiO2 lower than 100. The
      latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a
      formal randomized study. The bulk of data indicates that in severe acute
      respiratory distress syndrome, carefully performed prone positioning offers an
      absolute survival advantage of 10-17%, making this intervention highly
      recommended in this specific population subset.

PMID- 24134415
TI  - Two-dimensional speckle tracking-derived strain to distinguish acute coronary
      syndrome from a marked early repolarization in a patient with chest pain: a fancy
      gadget or a useful tool?
AB  - BACKGROUND: With a potential of detecting subtle myocardial injury, two
      dimensional (2D) speckle tracking-derived strain could help to distinguish
      between ischemic and nonischemic ST-segment elevation. Little is known if
      limitations of strain imaging could prevent its applicability in acute cardiac
      care settings. CASE PRESENTATION: We present a 56-year-old male with persistent
      ST-segment elevation in the inferolateral leads and suspected hypokinesia of the
      inferior wall. Semiautomated 2D speckle tracking strain analysis showed normal
      longitudinal peak systolic strain (LPSS) in all segments of the inferior wall,
      ruling out wall-motion abnormalities in this region. Stationary reverberations
      and spuriously low values of LPSS in the posterolateral wall required operator's
      expertise to distinguish pathological myocardial deformation from artifacts.
      Additional workup revealed that early repolarization pattern was mistaken for the
      inferior wall acute myocardial infarction in our patient. CONCLUSIONS:
      Semiautomated quantification of regional left ventricular function by 2D speckle
      tracking echocardiography could facilitate decision making even in the emergency
      settings. Due to intrinsic limitations of this novel method, its actual clinical
      value in acute cardiac care settings may depend on the expertise of the operator
      and is yet to be determined.

PMID- 24134416
TI  - A rare case of bullous contact dermatitis caused by severe organophosphorus
      pesticides poisoning.

PMID- 24134418
TI  - New concepts and insights into the role of radiation therapy in extracranial
      metastatic disease.
AB  - Stereotactic ablative radiotherapy (SABR) is a form of very precise radiotherapy
      that delivers high doses to tumors while sparing adjacent organs at risk. Recent
      data show that SABR is a low-toxic and highly effective local treatment for
      metastatic localizations in various organs, obtaining local control rates of
      approximately 80%. Experimental evidence also suggests that SABR may play an
      important therapeutic role in oligometastatic/oligorecurrent/oligoprogressive
      patients, a subset of cancer patients who are probably in an intermediate disease
      state between localized disease and widespread dissemination. There is a strong
      biological and clinical rationale in combining the high local control rates
      achievable with SABR with effective systemic therapies, and recent results of
      pilot studies indicate that SABR may have a potential impact on prognosis in this
      subgroup of patients, being 'curative' in around 20-25% of cases. This paper
      reviews and discusses basic concepts and clinical applications of SABR in
      oligometastatic patients. 

PMID- 24134419
TI  - Advances in biomarkers for esophageal cancer.
AB  - Cancer of the esophagus is an aggressive disease with early lymphatic and
      hematogenous dissemination and at present often considered as one clinical entity
      because of their comparable increasing incidence, prognosis and optimal treatment
      options. However, it is still a matter of debate whether these malignancies have
      the same pathogenesis and genotype. Despite recent advances, treatment of upper
      gastrointestinal malignancies remains a significant challenge. Molecular
      pathology has revealed many molecular mechanisms of disease progression, which
      are related to prognosis. Better knowledge of molecular bases may lead to new
      paradigms, improved prognostication, early diagnosis and individually tailored
      therapeutic options. This review summarizes the rationale, preclinical evidence,
      retrospective clinical analyses and the interim clinical data pertaining HER2
      therapy and many other molecular pathways. 

PMID- 24134420
TI  - Molecularly targeted therapy: toxicity and quality of life considerations in
      advanced colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common malignancy and cause of death
      from cancer among adults worldwide. In recent years, the use of 5-fluorouracil
      based regimens in combination with molecularly targeted agents has greatly
      expanded treatment options for patients with metastatic disease. With a more
      capillary use of this new class of agents comes the recognition of diverse
      adverse events related to disturbance of critical biological pathways involved in
      physiological functions. Proactive management and prevention of adverse events,
      with a focus on the necessary compromise between adverse events and tumor
      control, are often effective and allows for uninterrupted, full-dose therapy with
      targeted agents. Quality of life does not appear deteriorated, rather improved
      due to efficacy in prolonging wellness. 

PMID- 24134421
TI  - Antiangiogenic agents and chemotherapy in advanced non-small cell lung cancer: a
      clinical perspective.
AB  - Antiangiogenic agents represent a major advance in the management of patients
      with advanced non-small-cell lung cancer receiving chemotherapy. While
      bevacizumab has been available for first-line treatment, other drugs, such as
      nintedanib, recently demontrated significant activity in the second-line setting.
      This review covers most recent results with antiangiogenic treatments, focusing
      on data relevant for routine clinical practice; recent results potentially
      leading to new agents approval are discussed. While biomarkers are still awaited
      to better-select patients for these approaches, the development of antiangiogenic
      agents represent a model for implementation in thoracic oncology, while
      highlighting the promise of a better outcome for patients with advanced lung
      cancer. 

PMID- 24134422
TI  - Advanced non-small-cell lung cancer with epidermal growth factor receptor
      mutations: current evidence and future perspectives.
AB  - The identification of activating mutations in the tyrosine kinase domain of the
      EGF receptor (EGFR) predictive of response to tyrosine kinase inhibitors (TKIs)
      led to a therapeutic revolution in the treatment of patients with metastatic non
      small-cell lung cancer (NSCLC). To date, eight randomized clinical trials have
      demonstrated that first-line treatment with TKIs in advanced NSCLC patients
      harboring activating EGFR mutations is associated with significant improvement in
      response rate, progression-free survival, quality of life and tolerability,
      compared with platinum-based chemotherapy. These results prompted the EGFR TKIs
      as the current standard first-line treatment of patients with advanced NSCLC
      harboring activating EGFR mutations. However, there are several questions that
      need to be addressed, including the best choice among different EGFR TKIs, the
      treatment of resistant disease and of patients with specific clinical conditions.
      Ongoing and future, well-designed trials should answer all these questions. 

PMID- 24134423
TI  - HER2 and lung cancer.
AB  - In non-small-cell lung cancer (NSCLC), the identification of oncogenic driver
      mutations led to the definition of different clinical entities with different
      therapeutic opportunities, as demonstrated in patients harboring EGF receptor
      (EGFR) mutations or anaplastic lymphoma kinase translocations. Human EGFR2 (or
      HER2) has an established role as a prognostic and predictive factor in breast
      cancer. Although HER2 deregulation, including overexpression, amplification and
      mutation, has been described in NSCLC, its role as a therapy biomarker remains
      undefined. In the last few years, there has been a growing interest on HER2
      mutation, with few anecdotal or retrospective studies suggesting a relevant role
      for this biomarker. This review discusses the prognostic and predictive impact of
      HER2 deregulation and the clinical implications of anti-HER2 strategies in NSCLC.

PMID- 24134424
TI  - Single-stage application of a novel decellularized dermis for treatment-resistant
      lower limb ulcers: positive outcomes assessed by SIAscopy, laser perfusion, and
      3D imaging, with sequential timed histological analysis.
AB  - We present results of an original clinical study investigating efficacy of a
      decellularized dermal skin substitute (DCD) as part of a one-stage therapeutic
      strategy for recalcitrant leg ulcers. Twenty patients with treatment-resistant
      ulcers underwent hydrosurgical debridement, after which DCD was applied and
      covered with negative pressure dressings for 1 week. Participants were reviewed
      on seven occasions over 6 months. 3D photography, full-field laser perfusion
      imaging, spectrophotometric intracutaneous analysis, and sequential biopsies were
      used to monitor healing. Mean ulcer duration and surface area prior to DCD
      placement were 4.76 years (range 0.25-40 years) and 13.11 cm(2) (range 1.06-40.75
      cm(2)), respectively. Seventy percent of ulcers were venous. Surface area
      decreased in all patients after treatment (range 23-100%). Mean reduction was 87%
      after 6 months, and 60% of patients healed completely. Wound bed hemoglobin flux
      increased significantly 6 weeks after treatment (p = 0.005). Histological and
      immunohistochemical analysis confirmed progressive DCD integration with
      colonization by host fibroblasts, lymphocytes, and neutrophils, resulting in
      fibroplasia, reepithelialisation, and angiogenesis, with correlating raised CD31,
      collagen I, and collagen III levels. Subgroup analysis showed differing cellular
      behavior depending on wound duration, with delayed angiogenesis, reduced collagen
      deposition, and smaller reductions in surface area in ulcers present for over 1
      year. The stain intensities of immunohistochemical markers including fibronectin,
      collagen, and CD31 differed depending on depth from the wound surface and
      presence of intact epithelium. DCD safely produced significant improvement in
      treatment-resistant leg ulcers. With no requirement for hospital admission,
      anesthetic, or autogenic skin grafting, this treatment could be administered in
      hospital and community settings.

PMID- 24134425
TI  - The relationship between the second to fourth digit ratio and acne vulgaris.
AB  - BACKGROUND: Although the pathophysiology of acne vulgaris (AV) is not clear,
      androgens are thought to play an important role in its development through either
      an increased level of circulating androgens or end-organ sensitivity. The ratio
      of the length of the second and fourth digit (2D : 4D) has been hypothesized to
      reflect prenatal androgen exposure and/or an individual's sensitivity to
      androgens, with a low 2D : 4D ratio suggesting high prenatal androgen exposure.
      Interestingly, the prenatal androgen peak time period coincides with both the
      development of the sebaceous gland and digits. OBJECTIVES: To determine the
      relationship between digit ratio and AV. METHODS: Vernier caliper was used to
      take digit measurements of both patients and controls. Acne severity was assessed
      by using the International Consensus Conference on Acne Classification System.
      RESULTS: Data of 251 patients with AV (67.7% female) and 120 healthy controls
      (72.5% female), aged 16-40 years, were analysed. The 2D : 4D ratios of female
      patients with AV were significantly lower than healthy females in both hands.
      However, there was no significant difference between male acne cases and
      controls. Acne severity was positively correlated with the left 2D : 4D ratios
      and mean 2D : 4D ratio, whereas the duration of acne was negatively correlated
      with the right 2D : 4D ratios in females. CONCLUSION: Our results support the
      anatomical evidence of in utero androgen exposure and/or an individual's
      sensitivity to androgens in patients with AV and suggest that the 2D : 4D ratio
      might be a predictor of acne development, duration, and severity grade, at least
      in female patients.

PMID- 24134426
TI  - Measuring preferences for analgesic treatment for cancer pain: how do African
      Americans and Whites perform on choice-based conjoint (CBC) analysis experiments?
AB  - BACKGROUND: Conjoint Analysis (CA) can serve as an important tool to study health
      disparities and unique factors underlying decision-making in diverse subgroups.
      However, methodological advancements are needed in exploiting this application of
      CA. We compared the internal and external predictive validity and inter-temporal
      stability of Choice-based-Conjoint (CBC) analysis between African-Americans and
      Whites in the clinical context of preferences for analgesic treatment for cancer
      pain. METHODS: We conducted a prospective study with repeated-measures at two
      time-points (T1 = baseline; T2 = 3-months). African-Americans (n = 102); and
      Whites (n = 139) with cancer-related pain were recruited from outpatient oncology
      clinics in Philadelphia. Informed by pilot work, a computer-assisted CBC
      experiment was developed using 5 attributes of analgesic treatment: type of
      analgesic; expected pain relief; type of side-effects; severity of side-effects;
      and out-of-pocket cost. The design included 2 choice alternatives, 12 random
      tasks, 2 holdout tasks, and maximum of 6 levels per attribute. The internal and
      external predictive validity of CBC was estimated using Root Likelihood (RLH) and
      Mean Absolute Error (MAE), respectively. Inter-temporal stability was assessed
      using Cohen's kappa. RESULTS: Whites predominantly traded based on "pain relief"
      whereas African-Americans traded based on "type of side-effects". At both time
      points, the internal validity (RLH) was slightly higher for Whites than for
      African-Americans. The RLH for African-Americans improved at T2, possibly due to
      the learning effect. Lexicographic (dominant) behavior was observed in 29% of
      choice datasets; Whites were more likely than African-Americans to engage in a
      lexicographic behavior (60% vs. 40%). External validity (MAE) was slightly better
      for African-Americans than for Whites at both time-points (MAE: T1 = 3.04% for
      African-Americans and 4.02% for Whites; T2 = 8.04% for African-Americans; 10.24%
      for Whites). At T2, the MAE increased for both groups possibly reflecting an
      increase in the complexity of pain treatment decision-making based on
      expectations (T1) as opposed to reality (T2). The inter-temporal stability was
      fair for CBC attributes between T1 and T2 (kappa = 0.28, 95% CI: 0.24-0.32) and
      was not predicted by demographics including race. CONCLUSIONS: While we found
      slight group differences, overall the internal and external predictive validity
      of CBC was comparable between African-Americans and Whites. We discuss some areas
      to investigate and improve internal and external predictive validity of CBC
      experiments.

PMID- 24134428
TI  - The maintenance of mitochondrial genetic variation by negative frequency
      dependent selection.
AB  - Mitochondrial genes generally show high levels of standing genetic variation,
      which is puzzling given the accumulating evidence for phenotypic effects of
      mitochondrial genetic variation. Negative frequency-dependent selection, where
      the relative fitness of a genotype is inversely related to its frequency in a
      population, provides a potent and potentially general process that can maintain
      mitochondrial polymorphism. We assessed the change in mitochondrial haplotype
      frequencies over 10 generations of experimental evolution in 180 seed beetle
      populations in the laboratory, where haplotypes competed for propagation to
      subsequent generations. We found that haplotypes consistently increased in
      frequency when they were initially rare and decreased in frequency when initially
      common. Our results have important implications for the use of mtDNA haplotype
      frequency data to infer population level processes and they revive the general
      hypothesis that negative frequency-dependent selection, presumably caused by
      habitat heterogeneity, may commonly promote polymorphism in ecologically relevant
      life history genes. 

PMID- 24134427
TI  - The policy of free healthcare for children under the age of 6 years in Vietnam:
      assessment of the uptake for children hospitalised with acute diarrhoea in Ho Chi
      Minh City.
AB  - OBJECTIVE: To assess the proportion of, and reasons for, households not utilising
      the policy of free healthcare for children under 6 years of age (FCCU6) for
      hospitalisation with diarrhoea, and assess the risk of catastrophic expenditure
      for households that forgo FCCU6 and pay out of pocket. METHODS: Invoices
      detailing insurance information and charges incurred from 472 hospitalised
      diarrhoeal cases in one paediatric hospital in Ho Chi Minh City were retrieved.
      Hospital charges and the utilisation of elective services were analysed for
      patients utilising and not utilising FCCU6. Associations between socio-economic
      factors with non-utilisation of FCCU6 were evaluated. RESULTS: Overall, 29% of
      patients were FCCU6 non-users. The FCCU6 non-users paid a median hospital charge
      of $29.13 (interquartile range, IQR: $18.57-46.24), consuming no more than 1.4%
      of a medium-income household's annual income. Seventy per cent of low-income
      FCCU6 non-users utilised less-expensive elective services, whereas only 43% of
      medium income patients and 21% of high-income patients did (P = 0.036). Patients
      from larger households and those with a parent working in government were more
      likely to use FCCU6. CONCLUSIONS: The rate of FCCU6 non-usage in this study
      population was 29%. A significant proportion of those that did not use FCCU6 was
      from lower income households and may perceive a justifiable cost-benefit ratio
      when forgoing FCCU6. Although a single diarrhoeal hospitalisation is unlikely to
      induce a catastrophic expenditure, FCCU6 non-usage may disproportionately
      increase the risk of catastrophic expenditure for lower income households over
      multiple illnesses.

PMID- 24134429
TI  - Lightweight, multifunctional polyetherimide/graphene@Fe3O4 composite foams for
      shielding of electromagnetic pollution.
AB  - Novel high-performance polyetherimide (PEI)/graphene@Fe3O4 (G@Fe3O4) composite
      foams with flexible character and low density of about 0.28-0.4 g/cm(3) have been
      developed by using a phase separation method. The obtained PEI/G@Fe3O4 foam with
      G@Fe3O4 loading of 10 wt % exhibited excellent specific EMI shielding
      effectiveness (EMI SE) of ~41.5 dB/(g/cm(3)) at 8-12 GHz. Moreover, most the
      applied microwave was verified to be absorbed rather than being reflected back,
      resulting from the improved impedance matching, electromagnetic wave attenuation,
      as well as multiple reflections. Meanwhile, the resulting foams also possessed a
      superparamagnetic behavior and low thermal conductiviy of 0.042-0.071 W/(m K).
      This technique is fast, highly reproducible, and scalable, which may facilitate
      the commercialization of such composite foams and generalize the use of them as
      EMI shielding materials in the fields of spacecraft and aircraft.

PMID- 24134430
TI  - Alterations in pain response are partially reversed by methylphenidate (Ritalin)
      in adults with attention deficit hyperactivity disorder (ADHD).
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by
      dysregulation of sensory processing and neurobiology of dopamine. Although
      cumulative evidence suggests that dopamine is involved in pain processing, pain
      perception in ADHD subjects and the effect of dopamine agonists such as
      methylphenidate (MP, Ritalin) on it have rarely been studied. AIMS: The aims of
      this study were to (1) psychophysically assess sensitivity to pain in ADHD
      subjects as compared to controls and (2) examine the effects of MP on pain
      response in ADHD subjects. METHODS: Thirty subjects with ADHD and 30 age- and
      gender-matched controls participated in a preliminary trial. Pain threshold,
      intensity, and tolerance in response to cold pain stimulation were measured for
      both groups (ADHD with no treatment). In addition, the ADHD group was reassessed
      following a single dose of MP treatment. RESULTS: The ADHD subjects "without MP"
      in comparison with controls displayed significantly shorter cold pain threshold
      (2.8 +/- 2.1 vs. 5.8 +/- 2.5 seconds, respectively, P < 0.001) and cold tolerance
      (21.8 +/- 22.3 vs. 62.8 +/- 59.8 seconds, respectively P < 0.001). No differences
      in pain intensities between the groups were found. Following MP treatment, both
      cold threshold and tolerance in the ADHD subjects increased significantly
      compared to those with no treatment (3.6 +/- 2.5 seconds, P = 0.011, and 46.4 +/-
      53.3 seconds, P < 0.001, respectively). CONCLUSIONS: These results suggest that
      adults with ADHD are more sensitive to pain compared with controls and that MP
      may exert antinociceptive properties in these subjects. Randomized, controlled
      trials are warranted to verify these findings.

PMID- 24134431
TI  - Plant growth-promoting potential of bacteria isolated from active volcano sites
      of Barren Island, India.
AB  - To elucidate the biodiversity of plant growth-promoting (PGP) bacteria in active
      volcano sites of Barren Island, India, a total of 102 bacteria were isolated and
      screened for their multifunctional PGP properties. The results revealed that 21
      isolates (20.6%) survived heat shock at 72 degrees C and 11 (10.8%) isolates were
      able to grow exposed to 25% NaCl (w/v). In assaying for PGP properties, 59
      (57.8%) isolates shown indole acetic acid (IAA) like substances production, 57
      isolates (55.9%) produced siderophore and 34 (33.3%) solubilized inorganic
      phosphate qualitatively. Whereas in the production of extracellular enzymes, 42
      isolates (41.2%) produced protease and amylase, 26 (25.5%) isolates produced
      lipase and 24 (23.5%) isolates produced cellulase. In antagonistic activity, 30
      isolates (29.4%) were found antagonistic against Macrophomina sp., 20 isolates
      (19.6%) against Rhizoctonia solani and 15 isolates (14.7%) against Sclerotium
      rolfsii. The results based on 16 rRNA gene sequencing revealed that the PGP
      bacteria belonged to 22 different species comprising 13 genera. Based on
      multifunctional properties, nine isolates were further selected to determine the
      PGP in brinjal and chilli seeds. Of the bacteria tested, the isolate BAN87 showed
      increased root and shoot length of both the crops followed in plant growth
      promotion by BAN86 and BAN43. The outcome of this research proves plausible
      practical applicability of these PGPB for crop production in soils of saline and
      arid environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The present research
      shows diverse plant growth-promoting (PGP) bacteria could be isolated from the
      active volcano site and suggests that volcano sites represent an ecological
      niche, which harbours a diverse and hitherto largely uncharacterized microbial
      population with yet unknown and untapped potential biotechnological applications,
      for example, plant growth promoters, as evidenced from this study. The outcome of
      this research may have a practical effect on crop production methodologies in
      saline and arid environment soils.

PMID- 24134432
TI  - Quality of life and anxiety in Turkish patients with anorectal malformation.
AB  - AIM: The aim of this study was to investigate quality of life (QoL) and anxiety
      level in Turkish children with anorectal malformation as well as the anxiety
      level of their mothers and the support group effects on anxiety. METHODS: A total
      of 87 children and their parents were included. They were grouped according to
      children's age: <8 years (group 1), 8-12 years (group 2) and >12 years (group 3).
      The anxiety of all mothers and of children in group 3 was assessed by
      Spielberger's State-Trait Anxiety Index-2. The QoL of children in groups 2 and 3
      was evaluated with the Ped-QL 4.0 test by self-report and proxy report. The QoL
      results in groups 2 and 3 were compared with age-matched controls. RESULTS:
      Mothers in groups 1 and 3 were more anxious than were those in group 2.
      Adolescents in group 3 had poorer QoL compared with controls by self- and proxy
      reports. A significant difference was observed in QoL between the children who
      did and those who did not soil. The anxiety level was significantly lower in
      parents who attended more than one meeting. CONCLUSIONS: High anxiety and poor
      QoL levels in adolescence may have been related to the growing importance of body
      image. The higher anxiety levels of mothers in group 1 could be explained by an
      encounter with a baby who was different from the imagined baby and the newness of
      illness. QoL may have been perceived as being worse than what it was for
      psychological reasons.

PMID- 24134433
TI  - Mixture modeling methods for the assessment of normal and abnormal personality,
      part I: cross-sectional models.
AB  - Over the past 75 years, the study of personality and personality disorders has
      been informed considerably by an impressive array of psychometric instruments.
      Many of these tests draw on the perspective that personality features can be
      conceptualized in terms of latent traits that vary dimensionally across the
      population. A purely trait-oriented approach to personality, however, might
      overlook heterogeneity that is related to similarities among subgroups of people.
      This article describes how factor mixture modeling (FMM), which incorporates both
      categories and dimensions, can be used to represent person-oriented and trait
      oriented variability in the latent structure of personality. We provide an
      overview of different forms of FMM that vary in the degree to which they
      emphasize trait- versus person-oriented variability. We also provide practical
      guidelines for applying FMM to personality data, and we illustrate model fitting
      and interpretation using an empirical analysis of general personality
      dysfunction.

PMID- 24134434
TI  - Human exposure to rabid free-ranging cats: a continuing public health concern in
      Pennsylvania.
AB  - Rabid free-ranging cats have been a public health concern in Pennsylvania since
      raccoon variant rabies first was recognized in the state in the early 1980s. Over
      the last decade, between 1.5 and 2.5% of cats submitted to Pennsylvania's state
      laboratories for rabies testing have been positive. In this report, we describe
      the extent of rabies in free-ranging cats in Pennsylvania. We also present two
      examples of human exposure to rabid free-ranging cats that occurred in
      Pennsylvania during 2010-2011 and the public health actions taken to address
      rabies exposure in the humans and animals. We then describe the concerns
      surrounding the unvaccinated and free-ranging cat population in Pennsylvania and
      possible options in managing this public and animal health problem. 

PMID- 24134435
TI  - Comparison of outcomes between endovascular treatment and bypass surgery in
      Takayasu arteritis.
AB  - OBJECTIVES: There is currently a lack of evidence regarding the optimal
      revascularization method for Takayasu arteritis (TA). This study compares
      outcomes between endovascular treatment and surgical therapy in TA patients
      requiring revascularization. METHOD: From September 1994 to January 2011, 235
      patients were diagnosed with TA according to the diagnostic criteria of the 1990
      American College of Rheumatology, and of these, arterial revascularizations were
      performed in 65 (27.7%). Symptomatic or angiographic recurrence and peri
      operative use of immunosuppressive drugs were investigated by retrospectively
      reviewing medical records. RESULTS: A total of 111 arterial lesions in the 65
      (27.7%) patients were revascularized during the follow-up period (median 3.2
      years, range 0.01-12.7 years). At the 2-year follow-up, the symptomatic
      recurrence rate was significantly higher in the endovascular treatment group
      (32.3% vs. 11.5%, p = 0.016), as was the incidence of angiographic recurrence
      (32.1% vs. 11.1%, p = 0.026). The symptomatic recurrence rate was not influenced
      by the need for peri-operative immunosuppressive drugs (20% vs. 34.1%, p = 0.34).
      CONCLUSIONS: In TA patients, surgical revascularization seems to be superior to
      endovascular treatment with regard to patency. Further investigation to identify
      novel and optimal arterial revascularization methods for TA patients should be
      undertaken.

PMID- 24134436
TI  - Chronic disease influences over 40 major life-changing decisions (MLCDs): a
      qualitative study in dermatology and general medicine.
AB  - BACKGROUND: Chronic disease not only impairs patients' psycho-social well-being
      but also influences major life-changing decisions (MLCDs). There is little
      information about the types of MLCDs affected and the long-term consequences.
      OBJECTIVES: The aims were to identify the MLCDs influenced by chronic disease, to
      define 'MLCD' and to suggest support strategies for patients taking MLCDs.
      METHODS: Adult dermatology patients explained how their chronic disease had
      influenced MLCDs in individual interviews. Adult patients from other medical
      specialities gave similar information by postal survey. NVivo8 software was used
      for qualitative analysis of data. Themes were categorized through a coding
      recoding iterative process. RESULTS: There were 308 evaluable responses (male
      55.2%; mean age = 51.8 years, mean disease duration = 19 years) from the 365
      (55.7%) responses to the 655 patient invitations. These were used to generate
      themes to conceptualize 'MLCDs'. The most frequently reported MLCDs in the
      dermatology interviews concerned career choice (66%), job (58%), choice of
      clothing (54%), relationships (52%), education (44%), stopping swimming (34%),
      moving abroad (32%), not socializing (34%), wearing make-up (22%) and having
      children (22%). In the postal survey early retirement (40.6%), impact on job
      (29.4%), having children (24.8%), career choice (22.4%) and relationships (15.5%)
      were most commonly reported. The number of MLCDs reported by individuals was
      inversely related to age. Forty-one affected MLCD themes were grouped into 18
      MLCD categories. A definition of MLCD was developed and strategies suggested to
      support patients. CONCLUSIONS: Chronic diseases influence a wide range of MLCDs.
      MLCDs are a novel domain in disease burden assessment. Clinicians' knowledge
      about this is important in patient management.

PMID- 24134437
TI  - Deciphering the catalysis-associated conformational changes of human adenylate
      kinase 1 with single-molecule spectroscopy.
AB  - Human adenylate kinase isoenzyme 1 (AK1) is the key enzyme in maintaining the
      cellular energy homeostasis. The catalysis-associated conformational changes of
      AK1 involve large-amplitude rearrangements. To decipher the conformational
      changes of AK1 at the single-molecule level, we tagged AK1 with two identical
      fluorophores, one near the substrate-binding site and the other at the boundary
      of the core domain. We found that magnesium ion binding to AK1 increases the
      structural heterogeneity of AK1, whereas ADP binding reduces the structural
      heterogeneity. We exploited the hidden Markov model to extract the underlying
      catalysis-associated conformational dynamics and determined thermodynamic
      parameters of the multiple catalytic pathways. The third-order correlation
      difference calculated from photon fluctuation traces reveals the irreversible
      nature of the conformational motions, suggesting that single-molecule AK1 is in a
      nonequilibrium steady state. This discovery offers a fresh viewpoint to look into
      the molecular mechanisms of cellular biochemistry. 

PMID- 24134438
TI  - Skin cancer prevention in annual performance of total skin examination,
      photoprotection counseling, and patient instruction of self-skin examination.
AB  - BACKGROUND: Prevention of skin cancer includes early diagnosis and
      photoprotection, such as by physician-performed total skin examination (TSE) and
      patient-performed self-skin examination (SSE). Hypothesizing that 90% of our
      patients receive an annual TSE, photoprotection counseling, and SSE instruction,
      we assessed the extent to which this was documented in patients' records. We also
      sought to identify differences in documentation of TSE, photoprotection
      counseling, and instruction on SSE with or without use of a dictation template
      prompting documentation. MATERIALS AND METHODS: Retrospective review of a random
      sample of 400 patients in an outpatient dermatology practice of a tertiary care
      academic medical center for any dermatology appointment between May 1 and July
      31, 2007. Exclusion criteria included refusal to undergo TSE, lack of access to
      skin (e.g., wheelchair-bound or in cast), or inappropriate visit type (e.g., for
      acne, psoriasis, or lupus). RESULTS: Of 400 randomly selected patients, 313 met
      inclusion criteria. The dictation template was used in 133; of these, 89%
      (119/133) had documentation in their clinical note of a TSE (exclusive of the
      buttocks or groin area), and 98% (130/133) had documentation of instruction on
      sun protection and SSE. Without use of the dictation template, these percentages
      dropped to 78% (140/180) and 20% (36/180), respectively. Physicians using a
      dictation template were more likely to document having conducted a TSE and
      instructed patients on photoprotection and SSE. CONCLUSIONS: A dictation template
      aids documentation of annual TSE and patient education efforts on photoprotection
      and SSE.

PMID- 24134439
TI  - Cytoprotective effects of opioids on irradiated oral epithelial cells.
AB  - Oral mucositis is a common side effect of chemotherapy and radiation therapy
      accompanied with acute inflammation and ulceration of the oral mucosa. Opioids
      can improve the wound healing of dermal and oral tissue when applied locally. The
      aim of this study was to investigate if morphine exhibits cytoprotective effects
      on oral epithelial cells postirradiation. Hence, oral epithelial cells were
      exposed to increasing doses (3-30 Gy) of ionization radiation. We assessed the
      effects of the radiation on cell viability, proinflammatory cytokine release
      (interleukin [IL]-1alpha, IL-6), and matrix metalloproteinase (MMP-1, -8, and -9)
      expression. As expected, radiation significantly impaired cell viability and
      morphology and resulted in enhanced IL release. However, morphine-treated cells
      consistently showed higher cell viability postirradiation: 9.19 +/- 1.16% after
      24 hours and 7.45 +/- 0.93% after 48 hours compared with the control. In terms of
      proinflammatory cytokines, the release of IL-1alpha and IL-6 was significantly
      reduced, too, being most pronounced at 48 hours postradiation. Additionally, we
      observed a significant reduction of MMP-1 and especially MMP-9 expression in
      morphine-treated cells. The results clearly indicate anti-inflammatory as well as
      cytoprotective effects of morphine on irradiated oral epithelial cells.
      Interestingly, the protective effects of morphine are not related to a decrease
      in cell apoptosis or necrosis. Before final conclusions can be drawn, further
      studies in more complex systems in vitro and in vivo are required. Nevertheless,
      these findings further underline the high potential of opioids for the treatment
      of topical wounds and inflammatory conditions.

PMID- 24134440
TI  - Magnetic properties of fluffy Fe@alpha-Fe2O3 core-shell nanowires.
AB  - : Novel fluffy Fe@alpha-Fe2O3 core-shell nanowires have been synthesized using
      the chemical reaction of ferrous sulfate and sodium borohydride, as well as the
      post-annealing process in air. The coercivity of the as-synthesized nanowires is
      above 684 Oe in the temperature range of 5 to 300 K, which is significantly
      higher than that of the bulk Fe (approximately 0.9 Oe). Through the annealing
      process in air, the coercivity and the exchange field are evidently improved.
      Both the coercivity and the exchange field increase with increasing annealing
      time (TA) and reach their maximum values of 1,042 and 78 Oe, respectively, at TA
      = 4 h. The magnetic measurements show that the effective anisotropy is increased
      with increasing the thickness of thealpha-Fe2O3 by annealing. The large values of
      coercivity and exchange field, as well as the high surface area to volume ratio,
      may make the fluffy Fe@alpha-Fe2O3 core-shell nanowire a promising candidate for
      the applications of the magnetic drug delivery, electrochemical energy storage,
      gas sensors, photocatalysis, and so forth. 

PMID- 24134441
TI  - Thromboembolism risk following recurrent miscarriage.
AB  - Normal pregnancy is associated with extensive changes in hemostasis such that the
      procoagulant effect becomes dominant. The evolutionary advantage of this
      hypercoagulability may be to counteract the inherent instability associated with
      hemochorial placentation, which is unique to human beings. However, overall,
      there is a four- to 10-fold increased thrombotic risk throughout gestation and
      the postpartum period. Certain inherited or acquired thrombophilic factors may
      predispose to arterial and/or venous thrombosis and have a possible association
      with pregnancy complications, including recurrent miscarriage (RM), which affects
      up to 5% of couples with childbearing desire. A subgroup of women with RM has
      been demonstrated to be in a prothombotic state before and after pregnancy. The
      long-term health implications of this hypercoagulability may imply an increased
      risk of ischemic heart disease. Moreover, the presence of antiphospholipid
      antibodies rather than thrombophilic genetic defects (i.e., factor V Leiden or
      prothrombin G202010A mutation) in patients with RM is a determinant of thrombotic
      events later in life, especially among those patients having also cardiovascular
      risk factors. This article highlights the thromboembolic risk in nonpregnant RM
      patients in different thrombophilic settings and the need for thromboprophylaxis
      among these patients. 

PMID- 24134442
TI  - Regional anaesthesia and cancer metastases: the implication of local
      anaesthetics.
AB  - Clinical and basic science studies have demonstrated the anti-inflammatory
      properties of local anaesthetics. Recent studies have begun to unravel molecular
      pathways linking inflammation and cancer. Regional anaesthesia is associated in
      some retrospective clinical studies with reduced risk of metastasis and increased
      long-term survival. The potential beneficial effects of regional anaesthesia have
      been attributed mainly to the inhibition of the neuroendocrine stress response to
      surgery and to the reduction in the requirements of volatile anaesthetics and
      opioids. Because cancer is linked to inflammation and local anaesthetics have
      anti-inflammatory effects, these agents may participate in reducing the risk of
      metastasis, but their mechanism of action is unknown. We demonstrated in vitro
      that amide local anaesthetics attenuate tumour cell migration as well as
      signalling pathways enhancing tumour growth and metastasis. This has provided the
      first evidence of a molecular mechanism by which regional anaesthesia might
      inhibit or reduce cancer metastases. 

PMID- 24134443
TI  - Do pre-hospital anaesthesiologists reliably predict mortality using the NACA
      severity score? A retrospective cohort study.
AB  - INTRODUCTION: The National Advisory Committee on Aeronautics' (NACA) severity
      score is widely used in pre-hospital emergency medicine to grade the severity of
      illness or trauma in patient groups but is scarcely validated. The aim of this
      study was to assess the score's ability to predict mortality and need for
      advanced in-hospital interventions in a cohort from one anaesthesiologist-manned
      helicopter service in Northern Norway. METHODS: All missions completed by one
      helicopter service during January 1999 to December 2009 were reviewed. One
      thousand eight hundred forty-one patients were assessed by the NACA score. Pre
      hospital and in-hospital interventions were collected from patient records. The
      relationship between NACA score and the outcome measures was assessed using
      receiver operating characteristic (ROC) curves. RESULTS: A total of 1533 patients
      were included in the analysis; uninjured and dead victims were excluded per
      protocol. Overall mortality rate of the patients with NACA score 1-6 was 5.2%.
      Trauma patients with NACA score 1-6 had overall mortality rate of 1.9% (12/625)
      and non-trauma patients 7.4% (67/908). The NACA score's ability to predict
      mortality was assessed by using ROC area under curve (AUC) and was 0.86 for all,
      0.82 for non-trauma and 0.98 for trauma patients. The NACA score's ability to
      predict a need for respiratory therapy within 24 h revealed an AUC of 0.90 for
      all patients combined. CONCLUSION: The NACA score had good discrimination for
      predicting mortality and need for respiratory therapy. It is thus useful as a
      tool to measure overall severity of the patient population in this kind of
      emergency medicine system.

PMID- 24134444
TI  - Limitations of medical treatment among patients attended by the rapid response
      team.
AB  - BACKGROUND: Rapid response teams (RRTs) are called to deteriorating ward patients
      in order to improve their outcome. The involvement of the team also in end-of
      life care issues needs to be addressed. Our objective was to evaluate the RRT
      with focus on limitations of medical treatment (LOMT). METHODS: Observational
      cohort study of RRT calls from 2005 to 2010 at a university hospital. RESULTS:
      There were 2189 calls in 1818 admissions. Six hundred forty-two patients (35.3%)
      were assigned LOMT, and in 296 cases (46.1%) it was documented on the same day as
      the first RRT call. In total, 152 calls were for patients where a decision was
      already in place. Among patients with multiple calls, 44.6% received limitations.
      Hospital mortality was 25.6% in total, 60.6% for patients with limitations and
      6.6% for patients without. Mortality at 180 days was 43.2% for the whole cohort,
      and 83.6% and 21.2% with and without limitations, respectively. Cardiac arrest
      rate has remained at the level of 0.82/1000 admissions since the introduction of
      the RRT. CONCLUSION: Patients attended by the RRT have high short- and long-term
      mortality. Distinction of when deteriorations may be amenable to treatment or
      when focus should be laid on palliative care is not always made in the wards.
      Many decisions of limitations are taken in close conjunction to the call,
      although limitations do not preclude repeated visits from the team, indicating a
      need to support wards that care for patients at end of life.

PMID- 24134445
TI  - The stability of a sulphite-free epidural analgesic solution containing fentanyl,
      bupivacaine, and adrenaline.
AB  - BACKGROUND: Thoracic epidural infusion analgesia is optimised by using a triple
      component infusion containing a local anaesthetic, an opioid, and adrenaline.
      Adrenaline in solution is prone to oxidation, and stabilisers, such as
      antioxidants (e.g. sulphites) or chelators (edetates), are therefore commonly
      added. Sulphites may, however, have unwanted effects, especially allergic
      reactions. The aim of this study was to evaluate the stability of an analgesic
      infusion solution for epidural administration free of sulphites, containing
      adrenaline, fentanyl, bupivacaine, and disodium edetate. METHODS: An epidural
      infusion solution containing adrenaline 2 MUg/ml, fentanyl 2 MUg/ml, bupivacaine
      1 mg/ml, and disodium edetate 0.18 MUg/ml was stored at 2-8 degrees C for 4.5
      months. A concentrate 11 times more potent, used for the production of the ready
      to-use solution, was stored at 2-8 degrees C for 9 months. Concentrations of the
      active ingredients were determined, pH was measured throughout the period, the
      clarity of the solutions was investigated, and the weight of the infusion bags
      recorded. RESULTS: After 4.5 months at 2-8 degrees C, the infusion solution
      contained adrenaline 97.5%, bupivacaine 100.9%, and fentanyl 102.6%. The pH
      stayed between 4.76 and 4.79, the solutions remained clear, and the weight was
      99.9% of that found initially. The solution was also stable for 7 days at room
      temperature. The concentrate was stable (> 90%) for 9 months at 2-8 degrees C.
      CONCLUSION: The solution containing adrenaline, fentanyl, and bupivacaine,
      stabilised with disodium edetate, is stable for several months at 2-8 degrees C,
      and at least for 7 days at room temperature without the addition of sulphites.

PMID- 24134448
TI  - Color stability of carious incipient lesions located in enamel and treated with
      resin infiltration or remineralization.
AB  - OBJECTIVE: In this in vitro study, the color change of artificial caries lesions
      in enamel was evaluated after resin infiltration (Icon((r)), DMG, Hamburg,
      Germany) or remineralization. METHODS: Bovine enamel specimens (n = 72) were
      randomly divided into four groups: G1 - exposure to demineralizing solution (32
      h) and resin infiltration; G2 - immersion in demineralizing solution and
      remineralization cycles (8 days); G3 - demineralizing solution (negative
      control); G4 - healthy/non-treated enamel (positive control). The groups were
      subdivided and immersed in: A (saliva), B (coffee), and C (wine). The baseline
      color was evaluated by spectrophotometer and repeated after 4 and 8 weeks, and
      after polishing, at the end of 8 weeks. The variation in color (?E) and lightness
      (?L) was analyzed by anova (two-way) and Tukey tests, and Friedman and Kruskal
      Wallis tests, respectively. RESULTS: All specimens underwent color and lightness
      change, irrespective of immersion medium. In coffee, G2 presented the lowest mean
      ?E (P < 0.05), compared with the other groups. In saliva, G3 presented the
      highest mean ?E, and G2 and G4 lower ?E means. CONCLUSION: Lesions infiltrated
      with Icon((r)) underwent greater color change when compared with remineralized
      lesions, which may represent an esthetic disadvantage for the first-mentioned
      treatment.

PMID- 24134450
TI  - Prognostic role of embolic burden assessed at computed tomography angiography in
      patients with acute pulmonary embolism: systematic review and meta-analysis.
AB  - BACKGROUND: In patients with acute pulmonary embolism (PE), risk stratification
      is indicated for tailoring of both diagnostic strategies and acute treatment.
      Whether embolic burden assessed at computed tomography (CT) angiography has a
      role in risk stratification in these patients is debated. OBJECTIVE: To
      systematically review and perform a meta-analysis to evaluate the role of CT
      assessed burden associated with embolic obstruction and embolic localization in
      the prognostic stratification of patients with acute PE. METHODS: We performed a
      systematic search in EMBASE and MEDLINE up until 30 June 2013. Studies reporting
      on the 30-day outcome of patients with confirmed PE and CT-assessed embolic
      burden were included. The study outcome was death. RESULTS: Thirty studies
      reporting on the prognostic value of CT-assessed embolic burden met the inclusion
      criteria for this systematic review; of these, 19 were included in the meta
      analysis. Five studies (2215 patients) were included in the analysis of
      localization: an association between embolus localization in the central arteries
      and 30-day mortality was found after heterogeneity was resolved (odds ratio [OR]
      2.24, 95% confidence interval [CI] 1.29-3.89, I(2)  = 0%). No correlation was
      observed between obstruction index (according to the Qanadli scoring system) and
      30-day mortality after heterogeneity was reduced (16 studies, 3884 patients, OR
      1.22, 95% CI 0.99-1.51, I(2)  = 27%). CONCLUSION: Localization of emboli assessed
      at CT angiography can be used for risk stratification in patients with acute PE.
      Moreover, no correlation was observed between obstruction index and prognosis.

PMID- 24134449
TI  - Nevirapine versus efavirenz-based antiretroviral therapy regimens in
      antiretroviral-naive patients with HIV and tuberculosis infections in India: a
      pilot study.
AB  - BACKGROUND: Administration of rifampicin along with nevirapine reduces the plasma
      concentration of nevirapine in human immunodeficiency virus positive individuals
      with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper
      drug than its alternative efavirenz, and might be beneficial in resource
      constrained settings. METHODS: A randomised open label trial was conducted at All
      India Institute of Medical Sciences, New Delhi, India. During the regimen of an
      antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to
      receive either nevirapine or efavirenz based ART with concomitant rifampicin
      based anti-tubercular therapy (ATT). Participants were followed for 24 months
      after starting ART. The end points were virological, immunological and clinical
      responses, and progression of HIV disease marked by failure of ART. RESULTS: Of
      the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were
      selected randomly to receive efavirenz based ART and 67 to receive nevirapine
      based ART. The virological failure rates in the overall population, and the
      nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2%
      (9/68), respectively (p =0.94). No significant difference was found between the
      groups in the rate of clinical, immunological or virological failures. The
      overall mortality was 17% with no significant difference between the two groups.
      Except for the lead in period on day 14, the mean nevirapine concentration
      remained above 3 mg/L. No association was found between plasma levels of
      nevirapine and incidence of unfavourable outcomes in this group. CONCLUSIONS:
      Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant
      difference, irrespective of whether efavirenz or nevirapine was used. Therefore,
      nevirapine based ART could be an alternative in the resource limited settings in
      patients with HIV and tuberculosis co-infection. TRIAL REGISTRATION: NCT No.
      01805258.

PMID- 24134451
TI  - Identifying the factors contributing to the severity of truck-involved crashes.
AB  - To address the dilemma between the need for truck transportation and the costs
      related to truck-involved crashes, the key is to identify the risk factors that
      significantly affect truck-involved crashes. The objective of this research is to
      estimate the effects of the characteristics of traffic, driver, geometry, and
      environment on severity of truck-involved crashes. Based on four crash severity
      categories (fatal/incapacitating, non-incapacitating, possible injury, and no
      injury/property damage only), a multinomial logit model is conducted to identify
      the risk factors. The investigation of risk ratios indicates that lower traffic
      volume with higher truck percentage is associated with more serious traffic crash
      with fatal/incapacitating injury while a non-standard geometric design is the
      main cause of non-incapacitating crashes. The influences of weather are
      significant for the possible-injury crashes while driver condition is the
      principal cause of no-injury/property-damage-only crashes. In addition, the
      statistical results demonstrate that the influence of the truck percentage is
      significant. One-unit change in the truck percentage will cause more than one
      times probability of being in an injury. 

PMID- 24134452
TI  - Pulmonary vein stenosis assessed by three-dimensional transesophageal
      echocardiography.

PMID- 24134453
TI  - Increase in sagittal depth of the bony nasopharynx following maxillary
      protraction in patients with unilateral cleft lip and palate.
AB  - Objective : To study the change in the sagittal depth of the bony nasopharynx in
      patients with unilateral cleft lip and palate (UCLP), following maxillary
      protraction using reverse headgear. Methods : Nineteen patients (14 male, five
      female; aged 9.36 +/- 2.89 years) with repaired complete UCLP underwent maxillary
      protraction with a Delaire type reverse headgear at a tertiary-care referral
      teaching hospital. Control data were taken from five patients (four male, one
      female; aged 8.25 +/- 2.25 years) who did not receive any orthopedic/orthodontic
      treatment for a similar duration of time as the treated patients. Average
      treatment/observation period was 11.71 +/- 3.39 months for the treated patients
      and 12.40 +/- 2.60 months for the untreated subjects. Changes in the sagittal
      bony nasopharynx depth were measured by comparing pretreatment (T1) and
      posttreatment (T2) lateral cephalograms. Correlations between the changes in the
      bony nasopharynx depth and in other variables measured in the treated patients
      were analyzed. An exploratory analysis of differences in the changes from T1 to
      T2 between the treated patients and untreated subjects was also conducted.
      Results : The favorable skeletal changes seen in SNA and ANB following maxillary
      protraction were accompanied by a significant increase in the sagittal depth of
      bony nasopharynx (1.74 +/- 1.10 mm; P < .001). This change was significant when
      compared with the data from the untreated subjects (P = .004). Correlations
      between the increase in bony nasopharynx depth and changes in other variables
      studied in the treated patients were weak and not statistically significant.
      Conclusion : Sagittal depth of the bony nasopharynx in patients with repaired
      UCLP increased following maxillary protraction therapy using reverse headgear. 

PMID- 24134454
TI  - Developing a medication communication framework across continuums of care using
      the Circle of Care Modeling approach.
AB  - BACKGROUND: Medication errors are a common type of preventable errors in health
      care causing unnecessary patient harm, hospitalization, and even fatality.
      Improving communication between providers and between providers and patients is a
      key aspect of decreasing medication errors and improving patient safety.
      Medication management requires extensive collaboration and communication across
      roles and care settings, which can reduce (or contribute to) medication-related
      errors. Medication management involves key recurrent activities (determine need,
      prescribe, dispense, administer, and monitor/evaluate) with information
      communicated within and between each. Despite its importance, there is a lack of
      conceptual models that explore medication communication specifically across roles
      and settings. This research seeks to address that gap. METHODS: The Circle of
      Care Modeling (CCM) approach was used to build a model of medication
      communication activities across the circle of care. CCM positions the patient in
      the centre of his or her own healthcare system; providers and other roles are
      then modeled around the patient as a web of relationships. Recurrent medication
      communication activities were mapped to the medication management framework. The
      research occurred in three iterations, to test and revise the model: Iteration 1
      consisted of a literature review and internal team discussion, Iteration 2
      consisted of interviews, observation, and a discussion group at a Community
      Health Centre, and Iteration 3 consisted of interviews and a discussion group in
      the larger community. RESULTS: Each iteration provided further detail to the
      Circle of Care medication communication model. Specific medication communication
      activities were mapped along each communication pathway between roles and to the
      medication management framework. We could not map all medication communication
      activities to the medication management framework; we added Coordinate as a
      separate and distinct recurrent activity. We saw many examples of coordination
      activities, for instance, Medical Office Assistants acting as a liaison between
      pharmacists and family physicians to clarify prescription details. CONCLUSIONS:
      Through the use of CCM we were able to unearth tacitly held knowledge to expand
      our understanding of medication communication. Drawing out the coordination
      activities could be a missing piece for us to better understand how to streamline
      and improve multi-step communication processes with a goal of improving patient
      safety.

PMID- 24134455
TI  - Oxidation products of doubly trimethylene-bridged tetrabenzyl p-phenylenediamine
      paracyclophane.
AB  - We report synthesis and investigation of doubly trimethylene-bridged tetrabenzyl
      p-phenylenediamine 1(Bz) in its singly and doubly charged redox states. The
      singly oxidized monoradical cation, which is a mixed-valence (MV) system with
      directly interacting charge-bearing units, shows broad and solvent-sensitive
      intervalence bands consistent with class II compounds according to the Robin-Day
      classification. The doubly oxidized diradical dication of 1(Bz) exists in the
      spin-paired singlet state with thermally accessible triplet state. It has similar
      conformations as the other dimeric p-phenylenediamines, such as derivatives 1(Me)
      and 1(Et), in both the solid-state and solution phases. The successful isolation
      of the single-crystalline 1(Bz)(2+) diradical dications with two different in
      nature counteranions, relatively highly coordinating SbF6(-) and weakly
      coordinating carborane [undecamethylcarborane HCB11Me11(-) (CB(-))], reveals the
      distinct effect of the nature of counterions on the structural features of
      diradical dication. Cyclic voltammetry measurements of 1(Bz) in dichloromethane
      reveal separation of the first and second oxidation potential by 0.12 V (2.8
      kcal/mol), indicating relatively stable mixed-valence state in the
      dichloromethane, whereas in the acetonitrile both the first and second oxidation
      potentials overlap into one unresolved redox peak with minimal separation. 

PMID- 24134456
TI  - Topical photodynamic therapy with 5-aminolevulinate for the treatment of tumor
      stage mycosis fungoides: a case report.

PMID- 24134457
TI  - Biodurability/retention of Libby amphiboles in a case of mesothelioma.
AB  - Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous
      materials) and can occur decades after first exposure. The present case study
      reports on tissue burden of fibrous dust in a person who used a vermiculite
      material (Zonolite) as an attic insulator some 50 years prior to her death. The
      exposure occurred in two construction/renovation projects in her private
      residencies. She potentially had exposures to wall board/joint compounds during
      renovations. She additionally was reported to occasionally be involved in
      occupational activity, including drilling holes in presumed asbestos-containing
      electrical boxes. The tissue burden analysis revealed the presence of
      noncommercial amphibole asbestos fibers and consistent presence in the lung and
      lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers
      in human tissue can be attributed to exposure to Libby vermiculite. This study
      illustrates that analytical transmission electron microscopy can distinguish
      these structures from "asbestos" fibers. Further, the findings indicate that a
      population of these structures is biodurable and retained in the tissue years
      after first/last exposure.

PMID- 24134458
TI  - Bone mineral density, growth, pubertal development and other parameters in
      Brazilian children and young adults with sickle cell anaemia.
AB  - OBJECTIVES: To evaluate the occurrence of low bone mineral density (BMD) and its
      relationship with clinical and laboratorial characteristics in children and young
      adults with sickle cell anaemia living in Northeast-Brazil, and to assess the
      role of radiography in diagnosing low BMD. METHODS: Bone mineral density of
      lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 27
      patients with Sickle cell anaemia (SCA) aged 7-28 years. Clinical history,
      calcium and calorie intake, laboratory measurements, anthropometrics and pubertal
      development were assessed, and X-rays were obtained. Z-scores and T-scores for
      weight, height, Body Mass Index (BMI) and BMD were calculated using age and
      gender matched reference data. RESULTS: Mean lumbar spine BMD Z-scores and T
      scores were -1.81 SD in boys and -0.80 SD in girls. BMD Z-scores were below -2 SD
      in 33.3% of girls and in 46.7% of boys. Low BMD (<-2 SD) occurred significantly
      more in patients with low height-for-age (P = 0.02), low weight-for-age (P =
      0.001) and low BMI-for-age (P = 0.006). No significant relationships were found
      between BMD and other clinical and laboratory parameters. Radiography had a
      sensitivity of 75% and a specificity of 36% to detect low BMD, and was considered
      not useful in this context. CONCLUSIONS: Patients with low height and/or low
      weight-for-age seem to be at high risk for developing low BMD.

PMID- 24134459
TI  - Conservative management of cervical pregnancy with embryonic heart activity by
      ultrasound-guided local injection: an eight case series.
AB  - OBJECTIVE: To evaluate the efficacy of conservative management of cervical
      pregnancy with embryonic heart activity by ultrasound-guided local injection.
      METHODS: Retrospective case series at University tertiary care Hospital. Eight
      patients diagnosed with cervical pregnancy with embryonic heart activity managed
      conservatively. The intervention was ultrasound-guided local injection of
      methotrexate (1 mg/kg) and potassium chloride (2 meq/mL). Measurements were
      occurrence of morbidity, necessity for further intervention, the initial titers
      of beta-hCG, interval of time in which the levels of beta-hCG became negative,
      period for regression of cervical pregnancy at ultrasound and future pregnancy.
      RESULTS: All patients were treated successfully. The initial levels of beta-hCG
      ranged from 3013 to 71199 mUI/mL. One case evaluated with infection. There was no
      need for additional intervention in our series study. The interval of time for
      the levels of beta-hCG becomes negative range from 2 to 12 weeks. The period for
      the regression of the cervical pregnancy at ultrasound range from 3 to 14 weeks.
      In two cases intrauterine pregnancies occurred after the treatment. CONCLUSION:
      Conservative management of cervical pregnancy with embryonic heart activity by
      ultrasound-guided injection is an effective treatment avoiding the need of
      further intervention.

PMID- 24134461
TI  - What explains variation in the impacts of exotic plant invasions on the nitrogen
      cycle? A meta-analysis.
AB  - Exotic plant invasions can notably alter the nitrogen (N) cycle of ecosystems.
      However, there is large variation in the magnitude and direction of their impact
      that remains unexplained. We present a structured meta-analysis of 100 papers,
      covering 113 invasive plant species with 345 cases of invasion across the globe
      and reporting impacts on N cycle-related metrics. We aim to explain heterogeneity
      of impacts by considering methodological aspects, properties of the invaded site
      and phylogenetic and functional characteristics of the invaders and the natives.
      Overall, plant invasions increased N pools and accelerated fluxes, even when
      excluding N-fixing invaders. The impact on N pools depended mainly on functional
      differences and was greater when the invasive plants and the natives differed in
      N-fixation ability, plant height and plant/leaf habit. Furthermore, the impact on
      N fluxes was related mainly to climate, being greater under warm and moist
      conditions. Our findings show that more functionally distant invaders occurring
      in mild climates are causing the strongest alterations to the N cycle. 

PMID- 24134460
TI  - Chemosensory functions for pulmonary neuroendocrine cells.
AB  - The mammalian airways are sensitive to inhaled stimuli, and airway diseases are
      characterized by hypersensitivity to volatile stimuli, such as perfumes,
      industrial solvents, and others. However, the identity and function of the cells
      in the airway that can sense volatile chemicals remain uncertain, particularly in
      humans. Here, we show that solitary pulmonary neuroendocrine cells (PNECs), which
      are morphologically distinct and physiologically undefined, might serve as
      chemosensory cells in human airways. This conclusion is based on our finding that
      some human PNECs expressed members of the olfactory receptor (OR) family in vivo
      and in primary cell culture, and are anatomically positioned in the airway
      epithelium to respond to inhaled volatile chemicals. Furthermore, apical exposure
      of primary-culture human airway epithelial cells to volatile chemicals decreased
      levels of serotonin in PNECs, and the led to the release of the neuropeptide
      calcitonin gene-related peptide (CGRP) to the basal medium. These data suggest
      that volatile stimulation of PNECs can lead to the secretion of factors that are
      capable of stimulating the corresponding receptors in the lung epithelium. We
      also found that the distribution of serotonin and neuropeptide receptors may
      change in chronic obstructive pulmonary disease, suggesting that increased PNEC
      dependent chemoresponsiveness might contribute to the altered sensitivity to
      volatile stimuli in this disease. Together, these data indicate that human airway
      epithelia harbor specialized cells that respond to volatile chemical stimuli, and
      may help to explain clinical observations of odorant-induced airway reactions. 

PMID- 24134462
TI  - Egg allergy: an update.
AB  - Egg allergy is the commonest infant food allergy both in Australia and world
      wide. The clinical presentation of egg allergy is varied - egg is involved in
      both IgE and non-IgE-mediated allergic reactions and has been implicated in
      conditions such as anaphylaxis, food protein-induced enterocolitis syndrome,
      atopic dermatitis and eosinophilic oesophagitis. The clinical presentation,
      pathophysiology and diagnosis as well as the natural history and management of
      egg allergy will be discussed. Current theories about primary prevention as well
      as potential future therapies are presented. Finally, practical information about
      egg allergy and immunisation is provided. 

PMID- 24134463
TI  - Syphilitic balanitis of Follmann.
AB  - BACKGROUND: Syphilitic balanitis of Follmann (SBF) is a rare condition that is
      considered as manifestation of primary syphilis. MATERIALS AND METHODS: A 28-year
      old heterosexual male patient was consulted for a diffuse indurated dark red
      erythema of the glans penis accompanied by bilateral inguinal lymphadenopathy.
      Serological tests for syphilis were found positive. Treatment consisting of a
      single intramuscular administration of 2.4 million units of benzathine-penicillin
      was followed by complete disappearance of erythema and induration of the glans
      within two weeks. RESULTS: Syphilitic balanitis of Follmann presents with
      variable clinical appearances, and primary chancre may be absent, associated
      with, or occur after the balanitis. Usually the inguinal lymphadenopathy is
      present, and syphilitic serology is positive or is going to become positive.
      Treatment is identical to that of primary syphilis. CONCLUSION: The recrudescence
      of syphilitic infection requires exclusion of SBF from the diagnosis of
      balanitis.

PMID- 24134464
TI  - Gene therapy with beta-defensin 2 induces antitumor immunity and enhances local
      antitumor effects.
AB  - Beta-defensins, small antimicrobial peptides, are involved in host immune
      responses to tumors. In this study, we used beta-defensin 2 (BD2) to explore the
      possible role of beta-defensins in cancer gene therapy. A recombinant plasmid
      expressing a secretable form of BD2 was constructed. The biological activities of
      BD2 in immature dendritic cells (iDCs) were tested in vitro and in vivo. The
      antitumor effects were investigated in three established tumor models. The
      secreted BD2 was detected and exhibited chemotactic activity in iDCs both in
      vitro and in vivo. Recruitment and activation of iDCs in tumor niches resulted in
      significant tumor growth inhibition. Adoptive transfer of splenocytes and
      depletion of immune cell subsets revealed that CD8(+) T lymphocyte responses
      mediated the increased tumor inhibition. Furthermore, we also found that
      chemotactic and maturation-inducing activities in iDCs in tumor milieu
      contributed to enhanced local antitumor effects. Our study indicates that gene
      therapy with BD2 can mediate specific antitumor immunity and augment local
      antitumor effects. Our study also suggested that beta-defensins may merit further
      exploration for cancer immunotherapy as promising immunogenes.

PMID- 24134465
TI  - Fabrication of CuInS2-sensitized solar cells via an improved SILAR process and
      its interface electron recombination.
AB  - Tetragonal CuInS2 (CIS) has been successfully deposited onto mesoporous TiO2
      films by in-sequence growth of InxS and CuyS via a successive ionic layer
      absorption and reaction (SILAR) process and postdeposition annealing in sulfur
      ambiance. X-ray diffraction and Raman measurements showed that the obtained
      tetragonal CIS consisted of a chalcopyrite phase and Cu-Au ordering, which
      related with the antisite defect states. For a fixed Cu-S deposition cycle, an
      interface layer of beta-In2S3 formed at the TiO2/CIS interface with suitable
      excess deposition of In-S. In the meantime, the content of the Cu-Au ordering
      phase decreased to a reasonable level. These facts resulted in the retardance of
      electron recombination in the cells, which is proposed to be dominated by
      electron transfer from the conduction band of TiO2 to the unoccupied defect
      states in CIS via exponentially distributed surface states. As a result, a
      relatively high efficiency of ~0.92% (V(oc) = 0.35 V, J(sc) = 8.49 mA cm(-2), and
      FF = 0.31) has been obtained. Last, but not least, with an overloading of the
      sensitizers, a decrease in the interface area between the sensitized TiO2 and
      electrolytes resulted in deceleration of hole extraction from CIS to the
      electrolytes, leading to a decrease in the fill factor of the solar cells. It is
      indicated that the unoccupied states in CIS with energy levels below EF0 of the
      TiO2 films play an important role in the interface electron recombination at low
      potentials and has a great influence on the fill factor of the solar cells.

PMID- 24134466
TI  - Dosimetric and efficiency comparison of high-dose radiotherapy for esophageal
      cancer: volumetric modulated arc therapy versus fixed-field intensity-modulated
      radiotherapy.
AB  - The aim of this study was to compare high-dose volumetric modulated arc therapy
      (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the
      treatment of patients with middle-thoracic esophageal cancer. Eight patients with
      cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning
      system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare,
      Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each
      case, and both techniques were used to deliver 50 Gy to the planning target
      volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans
      provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034),
      whereas the ff-IMRT plans provided more appropriate dose homogeneity to the
      PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT
      plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans.
      The delivery time was significantly shorter for the VMAT plans than for the ff
      IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor
      units. The VMAT technique required a shorter planning time than the ff-IMRT
      technique (3.8 +/- 0.8 hours vs. 5.4 +/- 0.6 hours, P = 0.011). The major
      advantages of VMAT plans are higher efficiency and an approximately 50% reduction
      in delivery time compared with the ff-IMRT plans, with comparable plan quality.
      Further clinical investigations to evaluate the use of high-dose VMAT for the
      treatment of esophageal cancer are warranted.

PMID- 24134467
TI  - Microstructure and optical properties of Ag/ITO/Ag multilayer films.
AB  - Transflective and highly conductive Ag/ITO/Ag multilayer films were prepared by
      magnetron sputtering on glass substrates. The microstructure and optical
      properties of Ag/ITO/Ag multilayer films were systematically investigated by X
      ray diffraction, scanning electron microscopy, and ultraviolet-visible
      spectroscopy. The optical properties of the multilayer films were significantly
      influenced by the thickness of the Ag surface layer from 3.0 to 12.6 nm. The
      multilayer film of Ag9.3nm/ITO142nm/Ag9.3nm shows the best comprehensive
      property. It could satisfy the requirement for transflective LCD. 

PMID- 24134468
TI  - Acne is an inflammatory disease and alterations of sebum composition initiate
      acne lesions.
AB  - Hyperseborrhoea has been considered as a major aetiopathogenetic factor of acne.
      However, changes in sebaceous gland activity not only correlate with seborrhoea
      but also with alterations in sebum fatty acid composition. Current findings
      indicate that sebum lipid fractions with proinflammatory properties and
      inflammatory tissue cascades are associated in the process of the development of
      acne lesions. The oxidant/antioxidant ratio of the skin surface lipids and
      alterations of lipid composition are the main players in the induction of acne
      inflammation. Nutrition may influence the development of seborrhoea, the
      fractions of sebum lipids and acne. Acne is an inflammatory disease probably
      triggered, among others, by proinflammatory sebum lipid fractions. 

PMID- 24134469
TI  - Distribution of protein Ramachandran psi (psi) angle using non-resonance visible
      raman scattering measurements.
AB  - Knowing the distribution of Ramachandran angles helps in understanding peptide
      and protein backbone conformation. Empirical relations are proposed to correlate
      the spectral profile of the amide III3 band, obtained from ultraviolet resonance
      Raman measurements (UVRR), with the Ramachandran dihedral psi angle distribution
      in small peptide and protein molecules, in different environmental conditions
      (Mikhonin et al. J. Phys. Chem. B 2006, 110, 1928-1943). It has also been used
      for more complicated structures, like large globular proteins and protein
      fibrils. In our work here, we use visible Raman spectra and available empirical
      relations to obtain similar correlations for human serum albumin, hen egg white
      lysozyme, and human gamma crystallin. We also report the dihedral angle
      distribution in fibrils and a denatured protein in an ethanol environment using
      the same spectroscopic technique. 

PMID- 24134470
TI  - Expression of candidate genes for residual feed intake in Angus cattle.
AB  - Residual feed intake (RFI) has been adopted in Australia for the purpose of
      genetic improvement in feed efficiency in beef cattle. RFI is the difference
      between the observed feed intake of an animal and the predicted feed intake based
      on its size and growth rate over a test period. Gene expression of eight
      candidate genes (AHSG, GHR, GSTM1, INHBA, PCDH19, S100A10, SERPINI2 and SOD3),
      previously identified as differentially expressed between divergent lines of high
      and low-RFI animals, was measured in an unselected population of 60 steers from
      the Angus Society Elite Progeny Test Program using quantitative real-time PCR.
      Results showed that the levels of gene expression were significantly correlated
      with RFI. The genes explain around 33.2% of the phenotypic variance in RFI, and
      prediction equations using the expression data are reasonably accurate estimators
      of RFI. The association of these genes with economically important traits, such
      as other feed efficiency-related traits and fat, growth and carcass traits, was
      investigated as well. The expression of these candidate genes was significantly
      correlated with feed conversion ratio and daily feed intake, which are highly
      associated with RFI, suggesting a functional role for these genes in modulating
      feed utilisation. The expression of these genes did not show any association with
      average daily gain, eye muscle area and carcass composition. 

PMID- 24134471
TI  - IgG4-related disease in a Chinese cohort: a prospective study.
AB  - OBJECTIVES: To report the clinical, laboratory, and histological characteristics
      in a cohort of 28 Chinese patients with immunoglobulin G4-related disease (IgG4
      RD). METHOD: The patients were admitted to, or were out-patients in, Peking Union
      Medical College Hospital (PUMCH) between January 2011 and May 2012 according to
      the criteria for IgG4-RD. Clinical presentations, imaging studies, serum Ig
      subclass assays, and histological examinations were performed in all patients.
      RESULTS: The 28 patients (male-to-female ratio 1.8:1) enrolled in this study had
      a mean age at onset of disease of 51.5 years and the duration of symptoms before
      diagnosis was 20.4 months; 57% of the patients presented with a history of
      allergic disease. The most common symptoms were salivary and lacrimal gland
      swelling, and abdominal pain. Most patients (93%) presented with multiple organ
      involvement. Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) levels were observed in 16 (57%) and seven (25%) patients, respectively.
      The mean serum IgG4 level was 1142.3 mg/dL (range 149-3870 mg/dL). Eosinophilia
      was noted in 11 (39%) patients. IgE levels were elevated in all of eight patients
      examined. Lymphocyte and plasma cell infiltration and IgG4-positive plasma cell
      infiltration, together with tissue fibrosis, were the predominant histological
      findings. Most patients (93%) were given prednisone (0.5-0.8 mg/kg/day).
      Immunosuppressive agents were administered in 19 (68%) patients. Patients were
      followed for a mean of 6.3 months; efficacy was noted in more than 90% of cases.
      CONCLUSIONS: IgG4-RD is a chronic, systemic, multiorgan inflammatory disorder.
      IgG4-RD patients generally response well to glucocorticoids but the treatment
      should be individualized.

PMID- 24134472
TI  - Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and
      Staphylococcus aureus colonization within and between pneumococcal-vaccine naive
      mother-child dyads.
AB  - BACKGROUND: A high prevalence of bacterial nasopharyngeal co-infections has been
      reported in children, however, such data is limited in adults. We examined the
      interaction of Haemophilus influenzae, Staphylococcus aureus and Streptococcus
      pneumoniae pharyngeal colonization in mother-child dyads. METHODS: Pneumococcal
      vaccine naive children and their mothers had pharyngeal swabs undertaken at 1.6,
      2.5, 3.5, 4.5, 7.4, 9.5, 12.5, 16.2 and 24.2 months of child's age. Swabs were
      cultured for S. pneumoniae, H. influenzae and S. aureus using standard
      microbiologic methods. Multivariate generalized estimating equation-models were
      used to explore the associations of the three bacteria within and between
      children and their mothers. RESULTS: In children, the observed probability of co
      colonization was higher than expected. Well-defined associations in colonization
      between the bacteria were observed in children but not among mothers. In
      children, a synergistic association was observed between S. pneumoniae and H.
      influenzae (Adjusted odds ratio (AOR): 1.75, 95% CI: 1.32-2.32) and a negative
      association between S. pneumoniae and S. aureus (AOR: 0.51, 95% CI: 0.39-0.67) or
      H. influenzae and S. aureus (AOR: 0.24, 95% CI: 0.16-0.34) colonization.
      Additionally, all three bacteria had a higher likelihood of concurrent
      colonization. There was a strong association in colonization by the bacteria in
      children and their mothers, including increased likelihood of maternal
      colonization if the child was colonized by S. pneumoniae (AOR: 1.84, 95% CI: 1.28
      2.63) and H. influenzae (AOR: 6.34, 95% CI: 2.24-18.0). CONCLUSIONS: The effects
      of immunization of children with pneumococcal-conjugate-vaccine in settings such
      as ours needs monitoring with regard to potential changes of pharyngeal bacterial
      ecology which could occur in vaccinated and -unvaccinated age-groups.

PMID- 24134473
TI  - Development and validation of a computerized assessment form to support nursing
      diagnosis.
AB  - PURPOSE: Describe the development and validation of the Nursing Assessment Form
      (NAF), within a clinical nursing information system, to support nurses in the
      identification of nursing diagnoses. METHODS: Content validity and consensus on
      NAF contents were established using a panel of experts in nursing diagnosis and
      Delphi rounds. FINDINGS: Expert consensus was achieved to validate an instrument
      to support nurses in the process of nursing diagnoses identification.
      CONCLUSIONS: The use of the NAF can help nurses in diagnostic reasoning,
      facilitating the identification of the more suitable nursing diagnoses, and
      provide a basis for the best nursing interventions and outcomes. IMPLICATIONS FOR
      NURSING PRACTICE: The use of computerized decision support can improve the
      implementation of standardized terminology and the accuracy of nursing diagnosis.

PMID- 24134474
TI  - Three-dimensional echocardiography images showing anomalous pulmonary venous
      return in an adult with scimitar syndrome.

PMID- 24134475
TI  - 'It stays with me': the experiences of second- and third-year student nurses when
      caring for patients with cancer.
AB  - Little is known about student nurses experiences of nursing patients with cancer
      in the UK. With the increasing survival of people with cancer and with cancer no
      longer seen as a terminal illness it is useful to understand student nurses
      clinical experience when nursing those with cancer. This study takes a
      phenomenological approach involving three focus group interviews with 20 student
      nurses from the second and third year of their course in one centre in the UK.
      All the students had experience of caring for patients with cancer. The key
      themes emerging from the study were: Communication, Impact on Self, Lack of
      Support and End-of-Life-Care. Students emphasised the need to have more knowledge
      and support in relation to cancer care. They describe how they lack communication
      skills and found it difficult to handle their emotions. A number of students
      found the whole experience of caring for patients with cancer emotionally
      distressing and draining and they describe avoiding contact with these patients
      by using distancing and avoidance strategies. Student nurses need additional
      support through demystifying cancer, using reflective practice and good mentoring
      in the clinical area to enable students to feel supported, and develop confidence
      in their capacity for care for people with cancer. 

PMID- 24134476
TI  - Microporous brookite-phase titania made by replication of a metal-organic
      framework.
AB  - Metal-organic frameworks (MOFs) provide access to structures with nanoscale
      pores, the size and connectivity of which can be controlled by combining the
      appropriate metals and linkers. To date, there have been no reports of using MOFs
      as templates to make porous, crystalline metal oxides. Microporous titania
      replicas were made from the MOF template HKUST-1 by dehydration, infiltration
      with titanium isopropoxide, and subsequent hydrothermal treatment at 200  degrees
      C. Etching of the MOF with 1 M aqueous HCl followed by 5% H2O2 yielded a titania
      replica that retained the morphology of the parent HKUST-1 crystals and contained
      partially ordered micropores as well as disordered mesopores. Interestingly, the
      synthesis of porous titania from the HKUST-1 template stabilized the formation of
      brookite, a rare titania polymorph. 

PMID- 24134477
TI  - In reply.

PMID- 24134478
TI  - Epidemiology of orofacial clefts in the East of ireland in the 25-year period
      1984-2008.
AB  - Objective : To describe the epidemiology of orofacial clefts in the east of
      Ireland. Design and Setting : A descriptive epidemiologic study on 851 cases of
      orofacial cleft identified over a 25-year period from 1984 to 2008 from more than
      500,000 births. Results : There were 438 (51.5%) cases of cleft lip with or
      without cleft palate and 413 (48.5%) cases of cleft palate. The total birth
      prevalence was 16.0 per 10,000 births for all orofacial clefts, 8.2 for cleft lip
      with or without cleft palate, and 7.8 for cleft palate. Of all cases, 63.7%
      (542/851) occurred as isolated anomalies, 21.5% (183/851) were associated with
      multiple anomalies, and 14.8% (126/851) were associated with a syndrome or
      chromosomal anomaly. A significantly increasing trend over the 25-year period was
      observed for cleft lip with or without cleft palate associated with syndromes or
      chromosomal anomalies among mothers younger than 35 years but not in those older
      than 35 years. Conclusion : A slightly higher rate of orofacial clefts was
      observed in the east of Ireland than was observed in European and multinational
      studies during the study period, and there were higher rates of cleft palate. The
      rising trend in the proportion of mothers aged 35 years or older in Ireland is
      not contributing significantly to orofacial clefts associated with chromosomal
      syndromes. 

PMID- 24134479
TI  - Roadside observation of secondary school students' commuting to school in
      Vientiane, Laos.
AB  - To investigate modes of secondary school students' commuting to school and their
      unsafe driving practices in Laos, we conducted a roadside observation in front of
      the gate of a selected school in central Vientiane in December 2011. Of the 544
      students observed, the majority came to school on foot (43%), followed by
      motorcycle (36%), and bicycle (14%). Of the 195 students who commuted by
      motorcycle, 45 (23%) drove it themselves. Of the 150 students who commuted as
      pillion riders, 35 (23%) were driven by a student or another child driver. The
      prevalence of helmet use among students (3%) was much lower than adults (66%). It
      was common for adult drivers to wear a helmet but to leave student pillion riders
      unhelmeted on the same motorcycle. Carrying two or three pillion riders was also
      often observed. The study revealed the necessity for measures to promote safe
      travel to school. 

PMID- 24134480
TI  - Sequential injection method for rapid and simultaneous determination of 236U,
      237Np, and Pu isotopes in seawater.
AB  - An automated analytical method implemented in a novel dual-column tandem
      sequential injection (SI) system was developed for simultaneous determination of
      (236)U, (237)Np, (239)Pu, and (240)Pu in seawater samples. A combination of TEVA
      and UTEVA extraction chromatography was exploited to separate and purify target
      analytes, whereupon plutonium and neptunium were simultaneously isolated and
      purified on TEVA, while uranium was collected on UTEVA. The separation behavior
      of U, Np, and Pu on TEVA-UTEVA columns was investigated in detail in order to
      achieve high chemical yields and complete purification for the radionuclides of
      interest. (242)Pu was used as a chemical yield tracer for both plutonium and
      neptunium. (238)U was quantified in the sample before the separation for deducing
      the (236)U concentration from the measured (236)U/(238)U atomic ratio in the
      separated uranium target using accelerator mass spectrometry. Plutonium isotopes
      and (237)Np were measured using inductively coupled plasma mass spectrometry
      after separation. The analytical results indicate that the developed method is
      robust and efficient, providing satisfactory chemical yields (70-100%) of target
      analytes and relatively short analytical time (8 h/sample). 

PMID- 24134481
TI  - Revisiting vasopressin and heart failure.

PMID- 24134482
TI  - Effects of fullerenol C60(OH)24 nanoparticles on a single-dose doxorubicin
      induced cardiotoxicity in pigs: an ultrastructural study.
AB  - Cardioprotective effects of fullerenol C60(OH)24 nanoparticles (FNP) were
      investigated in pigs after a single treatment with doxorubicin (DOX). Semithin
      and ultrathin sections of myocardial tissue routinely prepared for transmission
      electron microscopy were analyzed. Extensive intracellular damage was confirmed
      in cardiomyocytes of DOX-treated animals. By means of ultrastructural analysis, a
      certain degree of parenchymal degeneration was confirmed even in animals treated
      with FNP alone, including both the oral and the intraperitoneal application of
      the substance. The cardioprotective effects of FNP in animals previously treated
      with DOX were recognized to a certain extent, but were not fully confirmed at the
      ultrastructural level. Nevertheless, the myocardial morphology of DOX-treated
      animals improved after the admission of FNP. Irregular orientation of myofibrils,
      myofibrillar disruption, intracellular edema, and vacuolization were reduced, but
      not completely eliminated. Reduction of these cellular alterations was achieved
      if FNP was applied orally 6 h prior to DOX treatment in a dose of 18 mg/kg.
      However, numerous defects, including the inner mitochondrial membrane and the
      plasma membrane disruption of certain cells persisted. In FNP/DOX-treated
      animals, the presence of multinuclear cells with mitosis-like figures resembling
      metaphase or anaphase were observed, indicating that DOX and FNP could have a
      complex influence on the cell cycle of cardiomyocytes. Based on this experiment,
      further careful increase in dosage may be advised to enhance FNP-induced
      cardioprotection. These investigations should, however, always be combined with
      ultrastructural analysis. The FNP/DOX interaction is an excellent model for the
      investigation of cardiomyocyte cell death and cell cycle mechanisms.

PMID- 24134483
TI  - Response to desmopressin in patients with mild hemophilia A caused by the F8
      c.1910A>G, p.Asn637Ser mutation.

PMID- 24134484
TI  - Sexual activity during pregnancy and prognosis of labor in Cameroonian women: a
      cohort study.
AB  - OBJECTIVE: Our aim was to assess the effects of sexual activity during pregnancy
      on the prognosis of labor. METHODS: It was a prospective cohort study of labor
      comparing 72 women declaring unprotected vaginal sexual intercourse after 37
      weeks of pregnancy consecutively recruited to 72 women claiming no sexual contact
      after 37 weeks of pregnancy also consecutively recruited. RESULTS: The sexually
      active group at term were significantly involved in more frequent heterosexual
      intercourse after 28 weeks pregnancy and before term (RR = 37.8; CI = 19.8
      515.4). Women sexually active were significantly admitted during the active phase
      of labor (RR = 2.4; IC = 1.6-5.3), with the fetal head at station 0 and more (RR
      = 1.5; CI = 1.3-5.2). They significantly had a shorter active phase (RR = 1.7; CI
      = 1.5-3.7) and a shorter second stage (RR = 1.5; CI = 1.2-3.3). They
      significantly had a normal pattern of labor (RR = 2.1; CI = 1.2-5.3), a higher
      rate of spontaneous deliveries (RR = 2.1; CI = 1.5-4.5), a lower rate of
      caesarean sections (RR = 0.46; CI = 0.1-0.8) and needed less oxytocin usage
      before expulsion (RR = 0.5; CI = 0.2-0.7). CONCLUSION: Sexual activity during
      pregnancy improves the prognosis of labor in Cameroonian women. In the absence of
      contraindications, consented unprotected heterosexual intercourse should be
      promoted in pregnant women.

PMID- 24134485
TI  - Cavernoma-related epilepsy: review and recommendations for management--report of
      the Surgical Task Force of the ILAE Commission on Therapeutic Strategies.
AB  - Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions
      present in 0.4-0.9% of the population. Epileptic seizures are the most frequent
      symptom in patients with CCMs and have a great impact on social function and
      quality of life. However, patients with CCM-related epilepsy (CRE) who undergo
      surgical resection achieve postoperative seizure freedom in only about 75% of
      cases. This is frequently because insufficient efforts are made to adequately
      define and resect the epileptogenic zone. The Surgical Task Force of the
      Commission on Therapeutics of the International League Against Epilepsy (ILAE)
      and invited experts reviewed the pertinent literature on CRE. Definitions of
      definitive and probable CRE are suggested, and recommendations regarding the
      diagnostic evaluation and etiology-specific management of patients with CRE are
      made. Prospective trials are needed to determine when and how surgery should be
      done and to define the relations of the hemosiderin rim to the epileptogenic
      zone. 

PMID- 24134487
TI  - In vitro activities of antifungal drugs against dermatophytes isolated in Tokat,
      Turkey.
AB  - BACKGROUND: In this study, we aimed to establish the in vitro antifungal
      susceptibilities of terbinafine, miconazole, itraconazole, ketoconazole,
      griseofulvin, and amphotericin B against dermatophyte isolates. METHODS: One
      hundred and seventy-seven clinical isolates were tested: Trichophyton rubrum (n =
      78), Trichophyton mentagrophytes (n = 49), Epidermophyton floccosum (n = 30),
      Trichophyton verrucosum (n = 16), and Trichophyton tonsurans (n = 4). The broth
      microdilution assay for antifungal susceptibility testing of dermatophytes was
      performed according to Clinical and Laboratory Standards Institute guidelines in
      the M38-A2 document. RESULTS: Our minimum inhibitory concentration (MIC) results
      showed that the values for terbinafine for all dermatophyte isolates were
      significantly lower than the values for amphotericin B, miconazole, itraconazole,
      ketoconazole, and griseofulvin. For T. rubrum isolates, amphotericin B was more
      active than miconazole, itraconazole, and ketoconazole. Among the antifungal
      drugs tested, griseofulvin had the highest minimum inhibitory concentration
      values for T. mentagrophytes isolates. CONCLUSION: Terbinafine was found to be
      the most effective antifungal drug against all tested dermatophyte isolates.
      Griseofulvin was the less active antifungal drug against T. mentagrophytes
      isolates. Performing antifungal susceptibility testing is especially important
      for screening the development of antifungal resistance.

PMID- 24134486
TI  - Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary
      inflammation in mice.
AB  - Although the effects of fish oil supplements on airway inflammation in asthma
      have been studied with varying results, the independent effects of the fish oil
      components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      administered separately, are untested. Here, we investigated airway inflammation
      and hyperresponsiveness using a mouse ovalbumin exposure model of asthma
      assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus
      DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty
      acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA
      contents (molar %) of 9.0 (+/- 0.6), 3.2 (+/- 0.2), 6.8 (+/- 0.5), and 0.01 (+/-
      0.0)%; DHA contents were 6.8 (+/- 0.1), 15.6 (+/- 0.5), 12.3 (+/- 0.3), and 3.8
      (+/- 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage
      (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for
      macrophages, IL-4, and IL-13, whereas TNF-alpha was lower in omega-3
      polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also
      had the highest airway resistance, which differed significantly from the EPA plus
      DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and
      BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin
      production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase
      pathways correlated significantly with BAL eosinophil levels. The proinflammatory
      effects of DHA suggest that the adverse effects of individual fatty acid
      formulations should be thoroughly considered before any use as therapeutic agents
      in asthma. 

PMID- 24134488
TI  - Asparagine assimilation is critical for intracellular replication and
      dissemination of Francisella.
AB  - In order to develop a successful infectious cycle, intracellular bacterial
      pathogens must be able to adapt their metabolism to optimally utilize the
      nutrients available in the cellular compartments and tissues where they reside.
      Francisella tularensis, the agent of the zoonotic disease tularaemia, is a highly
      infectious bacterium for a large number of animal species. This bacterium
      replicates in its mammalian hosts mainly in the cytosol of infected macrophages.
      We report here the identification of a novel amino acid transporter of the major
      facilitator superfamily of secondary transporters that is required for bacterial
      intracellular multiplication and systemic dissemination. We show that
      inactivation of this transporter does not affect phagosomal escape but prevents
      multiplication in the cytosol of all cell types tested. Remarkably, the
      intracellular growth defect of the mutant was fully and specifically reversed by
      addition of asparagine or asparagine-containing dipeptides as well as by
      simultaneous addition of aspartic acid and ammonium. Importantly, bacterial
      virulence was also restored in vivo, in the mouse model, by asparagine
      supplementation. This work unravels thus, for the first time, the importance of
      asparagine for cytosolicmultiplication of Francisella. Amino acid transporters
      are likely to constitute underappreciated players in bacterial intracellular
      parasitism. 

PMID- 24134489
TI  - Unexpected copper-catalyzed cascade synthesis of quinazoline derivatives.
AB  - The first example of a copper-catalyzed cascade reaction of (2
      aminophenyl)methanols with aldehydes using the combination of cerium nitrate
      hexahydrate and ammonium chloride has been developed, leading to a wide range of
      2-substituted quinazolines in moderate to excellent yields. The efficiency of
      this transformation was demonstrated by compatibility with a wide range of
      functional groups. Thus, the method represents a convenient and practical
      strategy for synthesis of 2-substituted quinazoline derivatives. 

PMID- 24134490
TI  - Thin-film photovoltaic cells: long-term metal(loid) leaching at their end-of
      life.
AB  - The photovoltaic effect of thin-film copper indium gallium selenide cells (CIGS)
      is conferred by the latter elements. Organic photovoltaic cells (OPV), relying on
      organic light-absorbing molecules, also contain a variety of metals (e.g., Zn,
      Al, In, Sn, Ag). The environmental impact of such technologies is largely
      unknown, in particular when the physical integrity deteriorates upon end-of-life,
      possibly facilitating cell constituent leaching. This study analyzed long-term
      inorganic leaching from damaged OPV and CIGS into different model waters.
      Leachate concentrations were put into perspective by calculating the predicted
      environmental concentrations (PEC) for several scenarios. Roof-top acidic rain
      runoff from CIGS was found to be the predominant emission source for metals and
      metalloids, with Cd released to such extents that PEC (173.4 MUg Cd L(-1)) would
      considerably exceed acute toxicity concentrations for Daphnia magna . Other PEC
      for CIGS (9.9 mg Mo L(-1) and 9.4 MUg Se L(-1)) were in the range of teratogenic
      effects. In contrast, OPV released little metals with calculated PEC being below
      even conservative drinking water guidelines. Time-resolved single-particle ICP-MS
      indicated that some metals (Zn, Mo, Ag) were in nanoparticulate form, raising
      nanotoxicity concerns. Leaching kinetics called for revision of existing
      standardized (accelerated) leaching protocols because long-term release was most
      relevant. 

PMID- 24134491
TI  - Effectiveness of a lifestyle exercise program for older people receiving a
      restorative home care service: study protocol for a pragmatic randomised
      controlled trial.
AB  - BACKGROUND: Restorative home care services help older people maximise their
      independence using a multi-dimensional approach. They usually include an exercise
      program designed to improve the older person's strength, balance and function.
      The types of programs currently offered require allocation of time during the day
      to complete specific exercises. This is not how the majority of home care clients
      prefer to be active and may be one of the reasons that few older people do the
      exercises regularly and continue the exercises post discharge.This paper
      describes the study protocol to test whether a Lifestyle Functional Exercise
      (LiFE) program: 1) is undertaken more often; 2) is more likely to be continued
      over the longer term; and, 3) will result in greater functional gains compared to
      a standard exercise program for older people receiving a restorative home care
      service. METHODS/DESIGN:  DESIGN: A pragmatic randomised controlled trial (RCT)
      design was employed with two study arms: LiFE program (intervention) and the
      current exercise program (control). SETTING: Silver Chain, a health and community
      care organisation in Perth, Western Australia. PARTICIPANTS: One hundred and
      fifty restorative home care clients, aged 65 years and older. MEASUREMENTS: The
      primary outcome is a composite measure incorporating balance, strength and
      mobility. Other outcome measures include: physical functioning, falls efficacy,
      and levels of disability and functioning. DISCUSSION: If LiFE is more effective
      than the current exercise program, the evidence will be presented to the service
      management accompanied by the recommendation that it be adopted as the generic
      exercise program to be used within the restorative home care service. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12611000788976.

PMID- 24134492
TI  - Route-dependent systemic and local immune effects following exposure to solutions
      prepared from titanium dioxide nanoparticles.
AB  - Nanoparticle titanium dioxide (nano-TiO2) is a white pigment widely used in
      foods, sunscreens, and other cosmetic products. However, it remains unclear
      whether exposure to nano-TiO2 results in immunosuppressive effects or induces a
      contact hypersensitivity response. To address these data gaps, studies were
      conducted with the hypothesis that nano-TiO2 exposure could alter immune
      responses. After 28 days of oral gavage, nano-TiO2 (1.25-250 mg/kg in 0.5%
      methylcellulose) produced no significant effects on innate, humoral, or cell
      mediated immune functions in female B6C3F1 mice. Furthermore, there were no
      effects on the weights of selected organs (spleen, thymus, liver, lung, and
      kidneys with adrenals). Following dermal exposure on the ears for 3 days, nano
      TiO2 (2.5-10% w/v in 4:1 acetone:olive oil) did not affect auricular lymph node
      cell proliferation, although an irritancy response was observed following
      treatment with 5% and 10% nano-TiO2. Dermal sensitization (2.5-10%) on the back
      and subsequent challenge (10%) on the right ear with nano-TiO2 produced no
      significant effects on percentage ear swelling in the Mouse Ear Swelling Test
      (MEST). However, when nano-TiO2 was injected subcutaneously along the mid-line on
      top of the head at 125-250 mg/kg (in 0.5% methylcellulose), significant increases
      in auricular lymph node cell proliferation resulted. These results demonstrate
      that immune effects of nano-TiO2 exposure are route-of-exposure dependent, and
      they suggest that irritancy and/or potential hypersensitivity responses may occur
      following parenteral exposure or dermal administration of nano-TiO2 to
      compromised skin.

PMID- 24134493
TI  - Interaction of H2 @C60 and nitroxide through conformationally constrained peptide
      bridges.
AB  - We synthesized two molecular systems, in which an endofullerene C60 ,
      incarcerating one hydrogen molecule (H2 @C60 ) and a nitroxide radical are
      connected by a folded 310 -helical peptide. The difference between the two
      molecules is the direction of the peptide orientation. The nuclear spin
      relaxation rates and the para -> ortho conversion rate of the incarcerated
      hydrogen molecule were determined by (1) H NMR spectroscopy. The experimental
      results were analyzed using DFT-optimized molecular models. The relaxation rates
      and the conversion rates of the two peptides fall in the expected distance range.
      One of the two peptides is particularly rigid and thus ideal to keep the H2 @C60
      /nitroxide separation, r, as large and controlled as possible, which results in
      particularly low relaxation and conversion rates. Despite the very similar
      optimized distance, however, the rates measured with the other peptide are
      considerably higher and thus are compatible with a shorter effective distance.
      The results strengthen the outcome of previous investigations that while the para
      -> ortho conversion rates satisfactorily obey the Wigner's theory, the nuclear
      spin relaxation rates are in excellent agreement with the Solomon-Bloembergen
      equation predicting a 1/r(6) dependence. 

PMID- 24134494
TI  - Modular mesoionics: understanding and controlling regioselectivity in 1,3-dipolar
      cycloadditions of Munchnone derivatives.
AB  - 1,3-Dipolar cycloadditions of mesoionic 1,3-dipoles (Munchnones, imino
      Munchnones, and phospha-Munchnones) with alkynes offer versatile, modular
      synthetic routes to pyrroles. Reactivity and regioselectivity differ markedly for
      different members of this series, and we report here the first general rationale
      for differences in reactivity by means of a systematic investigation of 1,3
      dipolar cycloadditions involving electron-poor and electron-rich alkynes.
      Competition kinetic measurements indicate that Munchnones and phospha-Munchnones
      are nucleophilic 1,3-dipoles that react most rapidly with electron-poor alkynes.
      However, the regioselectivities of cycloadditions are found to undergo an
      inversion as a function of alkyne ionization potential. The exact point at which
      this occurs is different for the two dipoles, allowing rational control of the
      pyrrole formed. The origins of these reactivities and regioselectivities are
      examined computationally. Frontier molecular orbital predictions are found not to
      be accurate for these reactions, but transition state calculations give correct
      predictions of reactivity and selectivity, the origins of which can be analyzed
      using the distortion/interaction model of reactivity. Cycloadditions with
      electron-poor alkynes are shown to favor the regioisomer that has either the most
      favorable TS interaction energy (Munchnones or imino-Munchnones) or the smallest
      TS distortion energy (phospha-Munchnones). Cycloadditions with more electron-rich
      aryl-substituted alkynes, on the other hand, generally favor the regioisomer that
      has the smaller TS distortion energy. These insights delineate the synthetically
      important distinctions between Munchnones and phospha-Munchnones: phospha
      Munchnones undergo highly regioselective cycloadditions with electron-poor
      alkynes that do not react selectively with Munchnones, and the reverse is true
      for cycloadditions of Munchnones with electron-rich alkynes. 

PMID- 24134495
TI  - Assessment of children with learning and behavioural problems: comparison of a
      multidisciplinary and sole paediatrician model.
AB  - AIMS: This study aimed to compare multidisciplinary (MD) versus sole
      paediatrician (SP) assessment models for children with learning and/or behaviour
      difficulties. METHODS: Children aged 4-12 years referred for an MD or SP
      assessment of learning and/or behavioural concerns were invited to participate.
      At baseline, parents completed surveys assessing child behaviour (Strengths and
      Difficulties Questionnaire; SDQ) and quality of life (QoL) (Pediatric Quality of
      Life Inventory 4.0; PedsQL). Following the assessment, parents completed a survey
      evaluating their satisfaction with the assessment. Parents completed a survey at
      3-4 months post-assessment assessing: (i) adherence to recommendations; (ii)
      perceived changes in child functioning; and (iii) child QoL and behaviour.
      RESULTS: The parents of 66 children (82% male) participated in the study. Parents
      reported satisfaction with both assessment models; however, parents in the MD
      group reported better understanding of their child's difficulties than the SP
      group (P = 0.03). Parents in the MD group were less likely to report that
      'recommendations were useful and practical' compared with the SP group (P =
      0.01). There was no significant change in child behaviour or QoL in either group
      from baseline to 3-4 months post-assessment. CONCLUSIONS: Parents attending both
      clinics were satisfied with the assessment process. MD assessment of children
      with suspected learning and/or behavioural concerns appears to have the
      additional benefit of helping families to better understand their child's
      difficulties. Fewer families attending MD clinics reported that recommendations
      were useful and practical compared with the SP model.

PMID- 24134496
TI  - Objective measures of right ventricular function during exercise: results of a
      pilot study.
AB  - BACKGROUND: A growing body of evidence seems to suggest that reduction in right
      ventricular (RV) systolic function is not only associated with both development
      of symptoms associated with pulmonary arterial hypertension (PAH) but also
      increased morbidity and adverse clinical outcomes. Recent data suggest that
      supine bicycle stress echocardiography (sBEE) is feasible and provides realistic
      resistance and compliance estimations. METHODS: The study design was a
      retrospective analysis of sBEE obtained for clinical indications of dyspnea on
      exertion or unexplained exercise intolerance. A total of 30 sBEE studies were
      included. The first 10 sBEE studies served as a calibration cohort not only to
      establish objective measures of RV performance but also to determine feasibility
      and reproducibility. The following 20 sBEE served as a validation cohort.
      RESULTS: Our results demonstrate that tricuspid annular plane systolic excursion
      and tricuspid annular systolic velocity, even when measured by an untrained
      reader, are reliable and accurate measures of the RV response to exercise during
      a sBEE protocol. Furthermore, measurements of RV myocardial performance (Tei
      index) or peak RV strain during exercise not only are time consuming but also
      simply unreliable and should not be utilized to evaluate RV function during sBEE.
      CONCLUSION: The results of our pilot study suggest that sBEE might be promising
      for detecting RV abnormalities during exercise. A larger prospective study is now
      needed to determine if TAPSE and tricuspid annular systolic velocity recorded
      during sBEE might be useful in assessing patients presenting with dyspnea during
      exercise or suspected of having PAH.

PMID- 24134497
TI  - Assessing the impact of genomic selection against hip dysplasia in the Labrador
      Retriever dog.
AB  - Many purebred dogs exhibit a higher prevalence of inherited diseases compared
      with non-purebred dogs. One of the most popular breeds in the UK is the Labrador
      Retriever, which has a high prevalence of hip dysplasia resulting in high costs
      for surgical operations and impaired animal welfare. Considering the many
      complications of highly managed populations, mainly due to breeder's conventions
      and the resulting population structure, is of great importance for the proper
      development of a strategy against the disease. In this study, we have compared
      the utilities and performances of both genomic and phenotypic selection against
      hip dysplasia in a simulated population with the characteristics of the British
      Veterinary Association and Kennel Club (BV /KC) hip dysplasia scheme. The results
      confirm the potential benefits of genomic selection by showing a moderate
      increase of 1.15-fold (assuming a realistic accuracy of r(2) = 0.5) in response
      to selection due to the higher accuracy (between 0.96- and 1.32-fold, considering
      0.35 <= r(2) <= 0.7) and more than a threefold increase when all the offspring in
      each litter are tested (between 3.25- and 4.55-fold, again considering 0.35 <=
      r(2) <= 0.7).

PMID- 24134498
TI  - Adalimumab maintains remission of Crohn's disease after up to 4 years of
      treatment: data from CHARM and ADHERE.
AB  - BACKGROUND: Therapies that maintain remission for patients with Crohn's disease
      are essential. Stable remission rates have been demonstrated for up to 2 years in
      adalimumab-treated patients with moderately to severely active Crohn's disease
      enrolled in the CHARM and ADHERE clinical trials. AIM: To present the long-term
      efficacy and safety of adalimumab therapy through 4 years of treatment. METHODS:
      Remission (CDAI <150), response (CR-100) and corticosteroid-free remission over 4
      years, and maintenance of these endpoints beyond 1 year were assessed in CHARM
      early responders randomised to adalimumab. Corticosteroid-free remission was also
      assessed in all adalimumab-randomised patients using corticosteroids at baseline.
      Fistula healing was assessed in adalimumab-randomised patients with fistula at
      baseline. As observed, last observation carried forward and a hybrid nonresponder
      imputation analysis for year 4 (hNRI) were used to report efficacy. Adverse
      events were reported for any patient receiving at least one dose of adalimumab.
      RESULTS: Of 329 early responders randomised to adalimumab induction therapy, at
      least 30% achieved remission (99/329) or CR-100 (116/329) at year 4 of treatment
      (hNRI). The majority of patients (54%) with remission at year 1 maintained this
      endpoint at year 4 (hNRI). At year 4, 16% of patients taking corticosteroids at
      baseline were in corticosteroid-free remission and 24% of patients with fistulae
      at baseline had healed fistulae. The incidence rates of adverse events remained
      stable over time. CONCLUSIONS: Prolonged adalimumab therapy maintained clinical
      remission and response in patients with moderately to severely active Crohn's
      disease for up to 4 years. No increased risk of adverse events or new safety
      signals were identified with long-term maintenance therapy. (clinicaltrials.gov
      number: NCT00077779).

PMID- 24134499
TI  - Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM
      staging systems.
AB  - BACKGROUND: Operative link on gastritis assessment (OLGA) and Operative link on
      gastric intestinal metaplasia assessment (OLGIM) staging systems have been
      proposed for gastric cancer (GC) risk estimation. AIM: To validate the OLGA and
      OLGIM staging systems in a region with high risk of GC. METHODS: This
      retrospective study included 474 GC patients and age- and sex-matched health
      screening control persons in a cancer centre hospital. We classified gastritis
      patterns according to the OLGA and OLGIM systems using the histological database
      that a pathologist prospectively evaluated using the updated Sydney system. GC
      risk according to the OLGA and OLGIM stages was evaluated using logistic
      regression analysis. RESULTS: More GC patients had OLGA stages III-IV (46.2%)
      than controls (26.6%, P < 0.001), particularly among patients with intestinal
      type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV
      were significantly associated with increased risk of GC [odds ratios (ORs), 2.09;
      P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The
      association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and
      4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV
      were significantly associated with increased risk of both intestinal-type (ORs,
      3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59,
      5.08 and 6.32 respectively) with a significantly increasing trend. CONCLUSION: As
      high OLGA and OLGIM stages are independent risk factors for gastric cancer, the
      staging systems may be useful for risk assessment in high-risk regions,
      especially for intestinal-type gastric cancer.

PMID- 24134500
TI  - Commentary: fibroblast growth factor 19 in patients with bile acid diarrhoea.

PMID- 24134501
TI  - Commentary: rabeprazole improves symptoms in patients with functional dyspepsia
      in Japan.

PMID- 24134502
TI  - Commentary: rabeprazole improves symptoms in patients with functional dyspepsia
      in Japan - author's reply.

PMID- 24134503
TI  - Letter: coeliac disease in inter-tropical Africa.

PMID- 24134505
TI  - The effect of a geriatric evaluation on treatment decisions for older cancer
      patients--a systematic review.
AB  - AIM: The aim of this systematic review is to summarise all available data on the
      effect of a geriatric evaluation on the multidisciplinary treatment of older
      cancer patients, focussing on oncologic treatment decisions and the
      implementation of non-oncologic interventions. METHODS: A systematic search in
      MEDLINE and EMBASE for studies on the effect of a geriatric evaluation on
      oncologic and non-oncologic treatment for older cancer patients. RESULTS:
      Literature search identified 1654 reports (624 from Medline and 1030 from
      Embase), of which 10 studies were included in the review. Three studies used a
      geriatric consultation while seven used a geriatric assessment performed by a
      cancer specialist, healthcare worker or (research) nurse. Six studies addressed a
      change in oncologic treatment, the initial treatment plan was modified in a
      median of 39% of patients after geriatric evaluation, of which two thirds
      resulted in less intensive treatment. Seven studies focused on the implementation
      of non-oncologic interventions based on the results of the geriatric evaluation;
      all but one reported that interventions were suggested for over 70% of patients,
      even in studies that did not focus specifically on frail older patients. In the
      other study, implementation of non-oncologic interventions was left to the cancer
      specialist's discretion. CONCLUSION: A geriatric evaluation has significant
      impact on oncologic and non-oncologic treatment decisions in older cancer
      patients and deserves consideration in the oncologic work-up for these patients.

PMID- 24134504
TI  - Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban
      Kampala-Uganda is not associated with cavitary disease.
AB  - BACKGROUND: Previous studies have shown that Mycobacterium tuberculosis (MTB)
      Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of
      tuberculosis (TB) in Uganda. Using a well characterized patient population, this
      study sought to determine whether there are clinical and patient characteristics
      associated with the success of the MTB Uganda family in Kampala. METHODS: A total
      of 1,746 MTB clinical isolates collected from 1992-2009 in a household contact
      study were genotyped. Genotyping was performed using Single Nucleotide
      Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4
      strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from
      patients with detailed clinical data. These data were used to seek associations
      between MTB lineage/sub-lineage and patient phenotypes. RESULTS: Three MTB
      lineages were found to dominate the MTB population in Kampala during the last two
      decades. Overall, MTB Uganda accounted for 63% (1,092/1,746) of all cases,
      followed by other Lineage 4 strains accounting for 22% (394/1,746), and Lineage 3
      for 11% (187/1,746) of cases, respectively. Seventy-three (4 %) strains remained
      unclassified. Our longitudinal data showed that MTB Uganda family occurred at the
      highest frequency during the whole study period, followed by other Lineage 4
      strains and Lineage 3. To explore whether the long-term success of MTB Uganda
      family was due to increased virulence, we used cavitary disease as a proxy, as
      this form of TB is the most transmissible. Multivariate analysis revealed that
      even though cavitary disease was associated with known risk factors such as
      smoking (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 3.33-6.84)
      and low income (aOR 2.1, 95% CI 1.47-3.01), no association was found between MTB
      lineage and cavitary TB. CONCLUSION: The MTB Uganda family has been dominating in
      Kampala for the last 18 years, but this long-term success is not due to increased
      virulence as defined by cavitary disease.

PMID- 24134506
TI  - Perceived barriers and facilitators to physical activity in men with prostate
      cancer: possible influence of androgen deprivation therapy.
AB  - While physical activity is beneficial for men with prostate cancer, too few
      perform sufficient activity for such benefit. This study examined perceptions of
      men with prostate cancer of their barriers and facilitators to physical activity,
      and how androgen deprivation therapy (ADT) may influence these perceptions. Two
      focus groups were conducted, involving six ADT and eight non-ADT patients
      respectively. Data were transcribed verbatim and themes developed using a general
      inductive thematic approach. Facilitators to physical activity common to both
      groups of cancer survivors included clinician and spousal involvement, with pre
      existing co-morbidities and increased age cited as barriers by both groups. The
      ADT subgroup cited personal involvement as a facilitator to physical activity,
      with fatigue, reduced motivation and a relative lack of specific advice from
      their clinician as additional barriers. The non-ADT subgroup had no additional
      facilitators to physical activity but cited time constraints as a barrier. These
      results highlight the important role that cancer clinicians and spouses play in
      promoting physical activity for men with prostate cancer and how ADT may
      influence their other facilitators and barriers. As physical activity is
      beneficial for prostate cancer survivors, especially those on ADT, cancer
      clinicians should regularly discuss physical activity with their patients. 

PMID- 24134507
TI  - Excited-state proton transfer of fluorescein anion as an ionic liquid component.
AB  - Fluorescent ionic liquids (FILs) incorporating the fluorescein anion have been
      prepared by anion exchange of the parent quaternary ammonium chloride (Quat(+)Cl(
      )) ionic liquid. By controlling the molar ratio of fluorescein to Quat(+)Cl(-),
      ionic liquids incorporating different prototropic forms of fluorescein were
      prepared. The 1:1 molar ratio ionic liquid (FIL1) is essentially composed of
      monoanionic fluorescein, while dianionic fluorecein is predominant in the FIL
      with a 1:2 molar ratio (FIL2). The fluorescence excitation spectrum of FIL2 is
      markedly different from its absorption spectrum. Absorption features the
      fluorescein dianion, while the excitation spectrum is exclusively due to the
      monoanion. In FIL1, the absorption and excitation spectra are both characteristic
      of the monoanion. In both FILs, emission of the dianion is observed upon
      excitation of the monoanion. This unusual behavior is interpreted in the context
      of a fast deprotonation of the monoanion in the excited state. The presence of
      residual water in the ionic liquid is important for the proton transfer process.
      By lowering the pH of FIL1, the transient proton transfer is inhibited, and the
      emission of the monoanion could be observed. The FILs have completely different
      spectroscopic properties from solvated fluorescein in Quat(+)Cl(-), where the
      prototropic equilibrium is shifted toward the neutral forms. 

PMID- 24134508
TI  - Hole defects and nitrogen doping in graphene: implication for supercapacitor
      applications.
AB  - One great challenge for supercapacitor is to achieve high energy capacity and
      fast charge/discharge rates simultaneously. Porous graphene with large surface
      area is a promising candidate for electrode materials of supercapacitor. Using
      first-principles calculations and non-equilibrium Green's function technique, we
      have explored the formation energies, mechanical properties, diffusion behaviors
      and electrical conductance of graphene sheets with various hole defects and/or
      nitrogen doping. Interestingly, graphene sheets with pyridinic-like holes
      (especially hexagonal holes) can be more easily doped with nitrogen and still
      retain the excellent mechanical properties of pristine graphene that is
      beneficial for the long cycle life. Porous graphene electrode with moderate hole
      diameter of 4.2-10 A facilitates efficient access of electrolyte and exhibit
      excellent rate capability. In addition, doping with nitrogen as electron donors
      or proton attractors leads to charge accumulation and generates higher
      pseudocapacitance. Transmission coefficients of N-doped graphene sheets with
      pyridinic-like holes are only moderately reduced with regard to that of pristine
      graphene and are insensitive to the detailed geometry parameters. Overall, N
      doped graphene with pyridinic-like holes exhibits exciting potentials for high
      performance energy storage in supercapacitor devices. 

PMID- 24134509
TI  - Three-dimensional magneto-photoluminescence as a probe of the electronic
      properties of crystal-phase quantum disks in GaAs nanowires.
AB  - Crystal-phase engineering has emerged as a novel method of bandgap engineering,
      made feasible by the high surface-to-volume ratio of nanowires. There remains
      intense debate about the exact characteristics of the band structure of the novel
      crystal phases, such as wurtzite GaAs, obtained by this approach. We attack this
      problem via a low-temperature angle-dependent magneto-photoluminescence study of
      wurtzite/zinc-blende quantum disks in single GaAs nanowires. The exciton
      diamagnetic coefficient is proportional to the electron-hole correlation length,
      enabling a determination of the spatial extent of the exciton wave function in
      the plane and along the confinement axis of the crystal-phase quantum disks.
      Depending on the disk nature, the diamagnetic coefficient measured in Faraday
      geometry ranges between 25 and 75 MUeV/T(2). For a given disk, the diamagnetic
      coefficient remains constant upon rotation of the magnetic field. Along with our
      envelope function calculation accounting for excitonic effects, we demonstrate
      that the electron effective mass in wurtzite GaAs quantum disks is heavy, mostly
      isotropic and results from mixing of the two lower-energy conduction bands with
      Gamma7 and Gamma8 symmetries. Finally, we discuss the implications of the results
      of the angle dependent magneto-luminescence for the likely symmetry of the
      exciton states. This work provides important insight in the band structure of
      wurtzite GaAs for future nanowire-based polytypic bandgap engineering. 

PMID- 24134510
TI  - PCSK9 and resistin at the crossroads of the atherogenic dyslipidemia.
AB  - The atherogenic dyslipidemia is a pathophysiological lipid triad, composed of
      high triglycerides and low-density lipoprotein and low high-density lipoprotein.
      The dyslipidemia is highly prevalent in individuals who are obese, insulin
      resistant and those with Type 2 diabetes and is the major contributing factor to
      the high atherosclerotic cardiovascular disease risk in these subjects. The
      primary initiating event in atherogenic dyslipidemia development is the hepatic
      overproduction of very-low-density lipoprotein (VLDL). The intracellular and
      extracellular protein triggers of hepatic VLDL production were not known until
      the recent identification of the causal roles of PCSK9 and resistin. Both PCSK9
      and resistin act in large part by targeting and reducing the hepatic degradation
      of VLDL apoB through distinctly different mechanisms. In the current review, we
      discuss both the individual roles and the interaction of these proteins in
      driving atherogenic dyslipidemia, and thus, atherosclerotic cardiovascular
      disease progression in humans. We further explore the important therapeutic
      implications of these findings. 

PMID- 24134511
TI  - Effects of nutritional stress and socio-economic status on maternal mortality in
      six German villages, 1766-1863.
AB  - We examined the effects of nutritional stress on maternal mortality arising from
      short-term economic crises in eighteenth-century and nineteenth-century Germany,
      and how these effects might have been mitigated by socio-economic status.
      Historical data from six German villages were used to assess how socio-economic
      conditions and short-term economic crises following poor harvests may have
      affected maternal mortality. The results show that 1 year after an increase in
      grain prices the risk of maternal death increased significantly amongst the wives
      of those working outside the agricultural sector, and more so than for the wives
      of those working on farms. Nutritional crises seem to have had a significantly
      stronger impact on maternal mortality in the period 2-6 weeks after childbirth,
      when mothers were most prone to infections and indirect, obstetrical causes of
      maternal death. The findings indicate that both nutritional stress and socio
      economic factors contributed to maternal mortality. 

PMID- 24134512
TI  - Adsorption of gas molecules on monolayer MoS2 and effect of applied electric
      field.
AB  - : Using first-principles calculations, we investigate the adsorption of various
      gas molecules (H2, O2, H2O, NH3, NO, NO2, and CO) on monolayer MoS2. The most
      stable adsorption configuration, adsorption energy, and charge transfer are
      obtained. It is shown that all the molecules are weakly adsorbed on the monolayer
      MoS2 surface and act as charge acceptors for the monolayer, except NH3 which is
      found to be a charge donor. Furthermore, we show that charge transfer between the
      adsorbed molecule and MoS2 can be significantly modulated by a perpendicular
      electric field. Our theoretical results are consistent with the recent
      experiments and suggest MoS2 as a potential material for gas sensing application.

PMID- 24134513
TI  - Asn3, a reliable, robust, and universal lock mass for improved accuracy in LC-MS
      and LC-MS/MS.
AB  - The use of internal calibrants (the so-called lock mass approach) provides much
      greater accuracy in mass spectrometry based proteomics. However, the
      polydimethylcyclosiloxane (PCM) peaks commonly used for this purpose are quite
      unreliable, leading to missing calibrant peaks in spectra and correspondingly
      lower mass measurement accuracy. Therefore, we here introduce a universally
      applicable and robust internal calibrant, the tripeptide Asn3. We show that Asn3
      is a substantial improvement over PCM both in terms of consistent detection and
      resulting mass measurement accuracy. Asn3 is also very easy to adopt in the lab,
      as it requires only minor adjustments to the analytical setup. 

PMID- 24134514
TI  - AIDS-related Kaposi's sarcoma in Brazil: trends and geopolitical distribution.
AB  - BACKGROUND: AIDS-related Kaposi's sarcoma (KS) is a unique model of the
      relationship between viral infection, immunity, environmental, and genetic
      factors in viral cancers. The goal was to determine the distribution of KS cases
      among Brazilian geopolitical regions, looking at the ecological relationship with
      median CD4 cell count. METHODS: Ecological study using Brazilian National
      Diseases Reporting Databases: 1982-2009. Subjects >= 13 years of age who have KS
      cited in their AIDS reporting form were selected, and demographic and HIV
      exposure data were collected. RESULTS: We found 11,731 KS cases in the period,
      with a prevalence of 2.4% among AIDS cases; 88% were male, and 68% lived in the
      Southeast region, which accounted for 59% of AIDS cases. The regional and
      national prevalence trends were similar, although the highest proportion among
      women was found in the North region, which has the lowest number of both AIDS and
      KS cases. Heterosexual transmission accounted for 87% of HIV among women compared
      to 18% among men. Fifty-seven percent of all KS cases were diagnosed before
      antiretroviral therapy (ART). Injection drug use accounted for 11% of KS cases.
      Median survival was 472 days before the ART era and 1482 after it (P < 0.001).
      Median CD4 counts increased in all regions in the period as ART coverage
      expanded, and a resulting correlating decline in KS cases was observed.
      CONCLUSIONS: Prevalence of KS declined after the introduction of ART in all
      regions of Brazil, suggesting individual protection conveyed by ART.

PMID- 24134515
TI  - Degradation of antibiotic activity during UV/H2O2 advanced oxidation and
      photolysis in wastewater effluent.
AB  - Trace levels of antibiotics in treated wastewater effluents may present a human
      health risk due to the rise of antibacterial activity in the downstream
      environments. Advanced oxidation has a potential to become an effective treatment
      technology for transforming trace antibiotics in wastewater effluents, but
      residual or newly generated antibacterial properties of transformation products
      are a concern. This study demonstrates the effect of UV photolysis and UV/H2O2
      advanced oxidation on transformation of 6 antibiotics, each a representative of a
      different structural class, in pure water and in two different effluents and
      reports new or confirmatory photolysis quantum yields and hydroxyl radical rate
      constants. The decay of the parent compound was monitored with HPLC/ITMS, and the
      corresponding changes in antibacterial activity were measured using bacterial
      inhibition assays. No antibacterially active products were observed following
      treatment for four of the six antibiotics (clindamycin, ciprofloxacin, penicillin
      G, and trimethoprim). The remaining two antibiotics (erythromycin and
      doxycycline) showed some intermediates with antibacterial activity at low
      treatment doses. The antibacterially active products lost activity as the UV dose
      increased past 500 mJ/cm(2). Active products were observed only in wastewater
      effluents and not in pure water, suggesting that complex secondary reactions
      controlled by the composition of the matrix were responsible for their formation.
      This outcome emphasizes the importance of bench-scale experiments in realistic
      water matrices. Most importantly, the results indicate that photosensitized
      processes during high dose wastewater disinfection may be creating
      antibacterially active transformation products from some common antibiotics. 

PMID- 24134516
TI  - Photocatalysis by 3,6-disubstituted-s-tetrazine: visible-light driven metal-free
      green synthesis of 2-substituted benzimidazole and benzothiazole.
AB  - s-Tetrazine based molecules were prepared for visible-light-driven organic
      transformations. The 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine (pytz) derivative
      shows visible light absorption and reversible one-electron reduction behavior. In
      the presence of pytz and aerial oxygen, aldehyde reacts with o-phenylenediamine
      or o-aminothiophenol under visible light irradiation at ambient temperature to
      produce corresponding 2-substituted benzimidazoles and benzothiazoles,
      respectively. Pytz catalyst demonstrates excellent catalytic activity for alkyl,
      aryl, organo-metallic substituted aldehydes and reducing sugar. The reaction
      yield is high for both the electron-donating and electron withdrawing
      substituents in aromatic aldehydes. The use of a metal-free catalyst and visible
      light energy, along with the mild reaction conditions, makes this reaction an
      environmentally benign and energy-saving chemical process. 

PMID- 24134517
TI  - Placenta accreta and beyond: Aesop is not Zeus.

PMID- 24134518
TI  - P58(IPK) inhibits coxsackievirus-induced apoptosis via the PI3K/Akt pathway
      requiring activation of ATF6a and subsequent upregulation of mitofusin 2.
AB  - Previously we found that prolonged endoplasmic reticulum (ER) stress caused by
      coxsackievirus B3 (CVB3) infection led to p58(IPK) downregulation and subsequent
      cell apoptosis. This finding implies that p58(IPK) expression benefits cell
      survival and counteracts CVB3-induced apoptosis. In testing this hypothesis, we
      first found that PI3K/Akt survival pathway is more sensitive than ERK1/2 in
      response to p58(IPK) expression. This finding was further verified by silencing
      p58(IPK) with specific siRNAs, which led to the significant suppression of
      phosphorylation of Akt (p-Akt) but not ERK1/2. Further, using CVB3-infected cell
      line expressing dominant negative ATF6a (DN-ATF6a), we found that expression of
      p58(IPK) and p-Akt was significantly reduced, which led to the decreased cell
      viability. However, when the DN-ATF6a cells were transiently transfected with
      p58(IPK) , an opposite result was obtained. Finally, by CVB3 infection of cells
      stably expressing p58(IPK) , we found that CVB3-induced mitochondria-mediated
      apoptosis was suppressed, which was evidenced by the reduced cytochrome c release
      and upregulation of the mitochondrial membrane protein mitofusin 2. However,
      silencing p58(IPK) with either specific siRNAs or DN-ATF6a sensitized cells to
      CVB3-induced apoptosis. These results suggest that p58(IPK) suppresses CVB3
      induced apoptosis through selective activation of PI3K/Akt pathway that requires
      activation of ATF6a and subsequently upregulates mitofusin 2. 

PMID- 24134519
TI  - Reference intervals of embryos/fetuses heart rate between 6 and 14 weeks of
      pregnancy.
AB  - OBJECTIVE: To determine reference intervals for the embryos/fetuses heart rate
      (HR) between 6 and 14 weeks of pregnancy. METHODS: A retrospective cross
      sectional study was carried in a single center with singleton pregnancies of
      embryos/fetuses with a crown-rump length (CRL) between 5 and 85 mm. The HR was
      assessed by real time M-mode or spectrum Doppler ultrasound. To evaluate the
      correlation between embryo/fetal HR and CRL, polynomial equations were
      calculated, with adjustment by the determination coefficient (R(2)). RESULTS: A
      total of 5867 pregnancies were assessed. The mean gestational age was 10.37 +/-
      2.12 weeks. The mean maternal age was 26.41 +/- 6.78 years. The mean embryo/fetal
      HR (bpm) for the CRL (mm) intervals 5?15; 15?25; 25?35; 35?45; 45?55; 55?65;
      65?75; 75?85 was 145.1 +/- 18.7; 167.2 +/- 10.1; 166.9 +/- 8.7; 165.5 +/- 6.9;
      162.2 +/- 6.8; 159.2 +/- 6.4; 157.1 +/- 6.4; 154.9 +/- 7.3; respectively. The
      following third-order equation best represented the correlation between
      embryo/fetal HR and CRL: HR = 119.25 + 3.596*CRL-0.07954*CRL(2 )+ 0.00051*CRL(3)
      (R(2 )= 0.36). CONCLUSION: Reference intervals of HR in embryos/fetuses in a
      large sample were determined. These reference intervals can be used in high-risk
      early pregnancy losses.

PMID- 24134520
TI  - Alterations in regional homogeneity assessed by fMRI in patients with migraine
      without aura stratified by disease duration.
AB  - BACKGROUND: Advanced neuroimaging approaches have been employed to prove that
      migraine was a central nervous system disorder. This study aims to examine
      resting-state abnormalities in migraine without aura (MWoA) patients stratified
      by disease duration, and to explore the neuroimaging markers for reflecting the
      disease duration. METHODS: 40 eligible MWoA patients and 20 matched healthy
      volunteers were included in the study. Regional homogeneity (ReHo) analysis was
      used to identify the local features of spontaneous brain activity in MWoA
      patients stratified by disease duration, and analysis was performed to
      investigate the correlation of overlapped brain dysfunction in MWoA patients with
      different disease duration (long-term and short-term) and course of disease.
      RESULTS: Compared with healthy controls, MWoA patients with long-term disease
      duration showed comprehensive neuronal dysfunction than patients with short-term
      disease duration. In addition, increased average ReHo values in the thalamus,
      brain stem, and temporal pole showed significantly positive correlations with the
      disease duration. On the contrary, ReHo values were negatively correlated with
      the duration of disease in the anterior cingulate cortex, insula, posterior
      cingulate cortex and superior occipital gyrus. CONCLUSIONS: Our findings of
      progressive brain damage in relation to increasing disease duration suggest that
      migraine without aura is a progressive central nervous disease, and the length of
      the disease duration was one of the key reasons to cause brain dysfunction in
      MwoA patients. The repeated migraine attacks over time result in resting-state
      abnormalities of selective brain regions belonging to the pain processing and
      cognition. We predict that these brain regions are sensitive neuroimaging markers
      for reflecting the disease duration of migraine patients without aura.

PMID- 24134521
TI  - A different kind of Christmas tree: anomalous origin of the right coronary artery
      from the pulmonary artery (ARCAPA).
AB  - Anomalous right coronary artery from the pulmonary artery (ARCAPA) is a rare
      congenital coronary anomaly that has an incidence of 0.002%. We report a case of
      a previously healthy female who presented to our hospital with pneumonia and was
      incidentally discovered to have ARCAPA. This was initially diagnosed on
      echocardiography by the unusual echocardiographic finding of multiple color flow
      Doppler signals around the right ventricular free wall and apex which were
      subsequently confirmed by angiography to be due to extensive collateral
      circulation between the left and right coronary arteries. This represents an
      unusual echocardiographic manifestation of this very rare condition. 

PMID- 24134522
TI  - Monoclonal antibodies targeting the antifibrinolytic activity of activated
      thrombin-activatable fibrinolysis inhibitor but not the anti-inflammatory
      activity on osteopontin and C5a.
AB  - BACKGROUND: Recently, anti-thrombin-activatable fibrinolysis inhibitor (TAFI)
      mAbs selectively inhibiting plasmin-mediated TAFI activation were shown to
      stimulate fibrinolysis in vitro and in vivo, suggesting, in contrast to other
      findings, that plasmin-mediated TAFI activation plays an important role in
      fibrinolysis regulation. OBJECTIVE: To further characterize the effects of two
      plasmin-specific anti-TAFI mAbs (MA-TCK11A9 and MA-TCK26D6) on TAFI-dependent
      inhibition of fibrinolysis. METHODS AND RESULTS: Both mAbs inhibited plasmin
      mediated but not thrombin/thrombomodulin-mediated TAFI activation, whereas
      neither inhibited the cleavage of hippuryl-arginine by activated TAFI (TAFIa).
      They stimulated tissue-type plasminogen activator-induced fibrinolysis in
      different clot lysis models through a TAFI-dependent mechanism, especially in the
      presence of thrombomodulin (TM), a condition in which TAFI is largely activated
      by the thrombin-TM complex. In a fibrinolysis-based TAFIa activity assay, both
      mAbs inhibited TAFIa, whereas other mAbs targeting thrombin-TM-mediated TAFI
      activation did not. The inhibition of TAFIa activity, however, was substrate
      specific, because neither mAb inhibited the cleavage of thrombin-activated
      osteopontin and C5a by TAFIa, thus sparing the anti-inflammatory activity of
      TAFIa. CONCLUSIONS: Our anti-TAFI mAbs, by selectively inhibiting TAFIa activity
      on fibrin, may represent the prototype of a new class of TAFI inhibitors with
      improved pharmacologic activity.

PMID- 24134523
TI  - De novo psychogenic nonepileptic attacks after adult epilepsy surgery: an
      underestimated entity.
AB  - We retrospectively assessed all patients in a large cohort of patients with
      epilepsy surgery at the National Hospital for Neurology and Neurosurgery (NHNN)
      over 12 years, to identify patients with postoperative psychogenic nonepileptic
      attacks (PNEA). Twenty-nine patients (23 women) were identified of a total of 790
      patients, a frequency of 3.7%. Female gender and presurgical psychiatric
      diagnosis, other than psychosis, were significant risk factors for PNEA
      development. In female patients with a preoperative psychiatric diagnosis the
      chance of developing PNEA after epilepsy surgery was 8.5%. PNEA developed between
      2 weeks and 10 years after epilepsy surgery, independently of outcome of
      epileptic seizures. In most cases, PNEA differed from the present or past
      epileptic seizures, and motor symptoms were the most common manifestations.
      Seizures after epilepsy surgery should be carefully evaluated. Physicians should
      consider the possibility of PNEA, especially in female patients with preoperative
      psychiatric comorbidity developing "atypical" seizures with motor manifestations
      postoperatively, even many years after epilepsy surgery. 

PMID- 24134524
TI  - Quasispecies tropism and compartmentalization in gut and peripheral blood during
      early and chronic phases of HIV-1 infection: possible correlation with immune
      activation markers.
AB  - HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal
      mucosa and peripheral blood cells (PBMC) from patients with early or chronic
      infection, with respect to viral heterogeneity, tropism compartmentalization and
      extent of immune activation. Seventeen HIV-1-infected combined antiretroviral
      therapy naive patients were enrolled (11 early infection and six chronic
      infection). V3 and nef genomic regions were analysed by ultra-deep
      pyrosequencing. Sequences were used to infer co-receptor usage and to construct
      phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble
      tumour necrosis factor receptor II (sTNFRII) levels were measured. Median
      diversity of HIV RNA was lower in patients with early infection versus chronic
      infection patients. Overall, direct correlation was observed between V3 diversity
      and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T
      cell count; median sCD14 and sTNFRII values were similar in early and chronic
      patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14.
      The proportion of patients harbouring X4 variants and median intra-patient X4
      frequency of proviral genomes tended to be higher in chronic infection than early
      infection patients. More pronounced compartmentalization of proviral quasispecies
      in gut compared with PBMC samples was observed in patients with early infection
      compared with chronic patients. The loss of gut/PBMC compartmentalization in more
      advanced stages of HIV infection was confirmed by longitudinal observation. More
      studies are needed to understand the pathogenetic significance of early HIV
      quasispecies compartmentalization and progressive intermixing of viral variants
      in subsequent phases of the infection, as well as the role of immune activation
      in tropism switch. 

PMID- 24134525
TI  - Lewy bodies under atomic force microscope.
AB  - Lewy bodies are the hallmark of Parkinson disease and their sophisticated
      analysis will undoubtedly elucidate the pathogenic process. They have been
      studied by using different microscopic tools. The authors have used atomic force
      microscopy (AFM) to study the ultramicrotom cut postmortem brain tissue of
      Parkinson disease patients. Under the same preparation conditions, they have
      found aggregated fibrillary nanostructures in Lewy bodies, as well as a loss of
      connections between neurons located in other parts of the substantia nigra.
      Although these results are preliminary and descriptive in nature, this paper
      reports the application of a novel and intriguing technique. Further studies
      including the study of cortical LB and Lewy neurites will be needed to determine
      the full potential of AFM in the study of the pathogenesis of cell death in
      Parkinson disease and other synucleinopathies.

PMID- 24134526
TI  - Maternal periconceptional exposure to cigarette smoking and congenital limb
      deficiencies.
AB  - BACKGROUND: Congenital limb deficiencies (LD)s are characterised by the failure
      or disruption in formation of limbs or digits. Epidemiological research on
      maternal exposure to cigarette smoke and LDs is inconclusive. METHODS: Data from
      the National Birth Defects Prevention Study were used to examine LDs and maternal
      exposure to active or passive cigarette smoke. Mothers of LD case (n = 906) and
      unaffected control (n = 8352) pregnancies from October 1997 through December 2007
      reported on exposure type and quantity. Logistic regression was used to estimate
      adjusted odds ratio (OR) and 95% confidence interval [95% CI]; interactions with
      folic acid (FA) intake were tested. RESULTS: For any LD, ORs were elevated for
      active (1.24 [95% CI 1.01, 1.53]), passive (home) (1.28 [95% CI 1.03, 1.59]), and
      'active and passive' (1.34 [95% CI 1.05, 1.70]) exposures. The ORs for
      longitudinal LDs were elevated for passive (home) (1.62 [95% CI 1.14, 2.31]) and
      'active and passive' (1.62 [95% CI 1.09, 2.41]) exposures. The OR for pre-axial
      LDs were elevated for any (1.39 [95% CI 1.01, 1.90]), active (1.53 [95% CI 1.03,
      2.29]), passive (home) (1.82 [95% CI 1.23, 2.69]), and 'active and passive' (1.87
      [95% CI 1.20, 2.92]) exposures. For lower limbs, ORs were elevated for passive
      (home) (1.44 [95% CI 1.01, 2.04]) and smoking 15 or more cigarettes/day (2.25
      [95% CI 1.27, 3.97]). Interactions showed that ORs for any passive smoke exposure
      were 0.43 and 0.59 higher in the absence of FA intake for any and terminal
      transverse LDs. CONCLUSIONS: Maternal active smoking and exposure to passive
      cigarette smoke emerged as a potential teratogen that affects limb and digit
      formation. FA was not found to mitigate the impact.

PMID- 24134527
TI  - Prospective study of maternal mid-pregnancy 25-hydroxyvitamin D level and early
      childhood respiratory disorders.
AB  - BACKGROUND: Studies suggest that prenatal vitamin D status may be inversely
      associated with lower respiratory tract infections (LRTIs) early in life. Studies
      of prenatal vitamin D status and development of asthma have inconsistent
      findings. METHODS: We examined the associations of maternal mid-pregnancy 25
      hydroxyvitamin D [25(OH)D] level with the frequency of LRTIs by 36 months and
      with current asthma at 36 months using the Norwegian Mother and Child Cohort
      Study. Maternal plasma 25(OH)D level was measured using liquid chromatography
      tandem mass spectrometry. Respiratory disorders were evaluated by maternal report
      through questionnaires. LRTIs were analysed in a random sample of 1248 children.
      Asthma was analysed using a case-control design, including 489 cases and 1183
      controls. Multivariable generalised linear models calculated adjusted measures of
      association. RESULTS: The median gestational week of sample collection was 18
      weeks (range 9, 35). The mean 25(OH)D level was 73.7 nmol/L (standard deviation
      23.7). Higher maternal mid-pregnancy 25(OH)D level was associated with a reduced
      risk of three or more LRTIs by 36 months vs. none, adjusted risk ratio 0.74 [95%
      confidence interval (CI): 0.58, 0.93] per 20 nmol/L increase. Associations were
      similar when examining the frequency of LRTIs by 18 months, and the frequency of
      LRTIs between 18 and 36 months. Maternal mid-pregnancy 25(OH)D level was not
      significantly associated with current asthma at 36 months, adjusted odds ratio
      0.91 [95% CI 0.81, 1.02] per 20 nmol/L increase. CONCLUSIONS: Higher maternal mid
      pregnancy 25(OH)D level was associated with a modestly reduced risk of recurrent
      LRTIs by 36 months, but was not associated with current asthma at 36 months.

PMID- 24134528
TI  - Effects of maternal prenatal smoking and birth outcomes extending into the normal
      range on academic performance in fourth grade in North Carolina, USA.
AB  - BACKGROUND: Research has documented the adverse relationship of child cognitive
      development with maternal prenatal smoking and poor birth outcomes. The
      potential, however, for maternal prenatal smoking to modify the association
      between birth outcomes and cognitive development is unclear. METHODS: We linked
      statewide North Carolina birth data for non-Hispanic white and non-Hispanic black
      children to end-of-grade test scores in reading and mathematics at fourth grade
      (n = 65 677). We fit race-stratified multilevel models of test scores regressed
      on maternal smoking, birth outcomes (as measured by continuous and categorical
      gestational age and birthweight percentile for gestational age), and their
      interaction, controlling for maternal- and child-level socio-economic factors.
      RESULTS: Smoking was consistently associated with decrements in test scores, and
      better birth outcomes were associated with improvements in test scores, even in
      clinically normal ranges. Test scores increased quadratically with improving
      birth outcomes among smoking and non-smoking mothers. Among non-Hispanic white
      children, the magnitude of the association between gestational age and test
      scores was larger for children whose mothers smoked during pregnancy compared
      with the non-smoking group. However, among non-Hispanic black children, birth
      outcomes did not appear to interact with maternal smoking on test scores.
      CONCLUSIONS: Maternal prenatal smoking may interact with birth outcomes on
      reading and mathematics test scores, particularly among non-Hispanic white
      children. Improvements in birth outcomes, even within the clinically normal
      range, may be associated with improved academic performance. Pregnancy-related
      exposures and events exert a significant and long-term impact on cognitive
      development.

PMID- 24134529
TI  - Herpes and other genitourinary infections, and gastroschisis and oestrogen.

PMID- 24134530
TI  - Plasma levels of advanced glycation endproducts are associated with type 1
      diabetes and coronary artery calcification.
AB  - BACKGROUND: Advanced glycation endproducts (AGEs) may play a role in the
      development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We
      studied plasma AGEs in association with T1DM and CAC, and whether or not the
      latter association could be explained by low-grade inflammation (LGI) or
      endothelial dysfunction (ED). METHODS: We studied 165 individuals with and 169
      without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma
      levels of protein-bound pentosidine, Nepsilon-(carboxymethyl)lysine (CML) and
      Nepsilon-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with
      fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP)
      was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI
      and ED, respectively. Associations were analyzed with ANCOVA and adjusted for
      age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR
      and T1DM. RESULTS: Individuals with T1DM had higher plasma levels of pentosidine,
      CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51
      (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102-107) vs. 93 (90-95) nmol/mmol LYS,
      p < 0.001; and 126 (118-134) vs. 113 (106-120) U/mL, p = 0.03, respectively.
      Levels of pentosidine were higher in individuals with T1DM with a moderate to
      high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67
      (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not
      attenuated by adjustment for LGI or ED. CONCLUSIONS: We found a positive
      association between pentosidine and CAC in T1DM. These results may indicate that
      AGEs are possibly involved in the development of CAC in individuals with T1DM.

PMID- 24134532
TI  - Comparison of the symptoms reported by post-operative patients with cancer and
      nurses' perception of patient symptoms.
AB  - The purpose of this study was to compare the symptoms reported by patients with
      cancer after palliative surgery and mechanical ventilation in an intensive care
      unit (ICU) with their primary nurses' perception of the symptoms. The study
      adopted a descriptive and correlational study design. The sample comprised 60
      Turkish patients with cancer who had been mechanically ventilated for 1-12 h at
      the ICU following palliative surgery. In addition to the patients' reports, the
      nurses (= 8) independently rated their own perceptions of the patients' symptoms.
      Data were collected using the Edmonton Symptom Assessment Scale (ESAS). The mean
      age of the sample was 62.28 years (SD = 15.02; range: 27-86). The mean score of
      the patients on the ESAS was 55.17 (SD = 26.16) and that of the nurses was 55.48
      (SD = 27.13). The study found no statistically significant differences between
      scores of patients' reports and nurses' assessments of symptoms, except for the
      category of pain. Patients reported more pain than the nurses' perceived (Z = 
      2.311, P = 0.021). Systematic and frequent symptom assessments of patients in
      ICUs after palliative surgical operations should be an integral part of nursing
      care.

PMID- 24134531
TI  - Efficacy and safety of lanthanum carbonate on chronic kidney disease-mineral and
      bone disorder in dialysis patients: a systematic review.
AB  - BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a
      common complication in CKD patients, particularly in those with end-stage renal
      disease that requires dialysis. Lanthanum carbonate (LC) is a potent, non
      aluminum, non-calcium phosphate binder. This systematic review evaluates the
      efficacy and safety of LC in CKD-MBD treatment for maintenance-dialysis patients.
      METHODS: A systematic review and meta-analysis on randomized controlled trials
      (RCTs) and quasi-RCTs was performed to assess the efficacy and safety of LC in
      maintenance hemodialysis or peritoneal dialysis patients. Analysis was performed
      using the statistical software Review Manager 5.1. RESULTS: Sixteen RCTs
      involving 3789 patients were identified and retained for this review. No
      statistical difference was found in all-cause mortality. The limited number of
      trials was insufficient to show the superiority of LC over other treatments in
      lowering vascular calcification or cardiovascular events and in improving bone
      morphology, bone metabolism, or bone turn-over parameters. LC decreased the serum
      phosphorus level and calcium * phosphate product (Ca * P) as compared to placebo.
      LC, calcium carbonate (CC), and sevelamer hydrochloride (SH) were comparable in
      terms of controlling the serum phosphorus, Ca * P product, and intact parathyroid
      hormone (iPTH) levels. However, LC resulted in a lower serum calcium level and a
      higher bone-specific alkaline phosphatase level compared with CC. LC had higher
      total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared
      with SH. LC-treated patients appeared to have a higher rate of vomiting and lower
      risk of hypercalcemia, diarrhea, intradialytic hypotension, cramps or myalgia,
      and abdominal pain. Meta-analysis showed no significant difference in the
      incidence of other side effects. Accumulation of LC in blood and bone was below
      toxic levels. CONCLUSIONS: LC has high efficacy in lowering serum phosphorus and
      iPTH levels without increasing the serum calcium. Current evidence does not show
      a higher rate of adverse effects for LC compared with other treatments, except
      for a higher incidence of vomiting. Moreover, LC accumulation in blood and bone
      was below toxic levels. Well-designed studies should be conducted to evaluate the
      long-term effects of LC.

PMID- 24134533
TI  - Haiti's food and drinking water: a review of toxicological health risks.
AB  - CONTEXT: The Republic of Haiti is a developing country in the Caribbean region
      with a history that challenges toxicologists, yet the historical panoply of
      toxicological hazards in Haiti has received little scholarly attention.
      OBJECTIVES: The primary objectives of this paper are to review what is known
      about Haiti's current toxicological hazards, with a focus on chronic food-borne
      aflatoxin exposure and heavy metal contamination of water resources, and to
      compare these with previous large-scale, acute exposures to toxic substances: the
      1995-1996 diethylene glycol (DEG) intoxications and the 2000-2001 ackee fruit
      poisonings. METHODS: MEDLINE/PUBMED and the library website of Cornell University
      were searched using the terms "Haiti" and either "heavy metals," "aflatoxin",
      "diethylene glycol", or "ackee". The search was inclusive of articles from 1950
      to 2012, and 15 out of the 37 returned were peer-reviewed articles offering
      original data or comprehensive discussion. One peer-reviewed article in press,
      two newspaper articles, two personal communications, and one book chapter from
      the personal databases of the authors were also referenced, making a total of 21
      citations. RESULTS: Elevated concentrations of aflatoxins (greater than 20
      MUg/kg) were documented for staples of the Haitian food supply, most notably
      peanut butters and maize. Human exposure to aflatoxin was confirmed with analysis
      of aflatoxin blood biomarkers. The implications of aflatoxin exposure were
      reviewed in the light of Haiti's age-adjusted liver cancer risk - the highest in
      the Caribbean region. Measurement of heavy metals in Port-au-Prince ground water
      showed contamination of lead and chromium in excess of the US Environmental
      Protection Agency's 15 MUg/L Action Level for lead and 100 MUg/L Maximum
      Contamination Level Goal for total chromium. The DEG contamination of paracetamol
      (acetaminophen) containing products in 1995-1996 claimed the lives of 109
      children and the 2000-2001 epidemic of ackee fruit poisoning resulted in 60 cases
      of intoxication. Lessons for the Haitian Government. The DEG and ackee epidemics
      overwhelmed local Haitian public health resources. Yet, periods of 8 and 4
      months, respectively, passed before the Haitian government sought assistance
      following the initial poisonings. To our knowledge, the Haitian government did
      not enact policy to promote drug safety and prevent future poisonings. This will
      not likely change in the near future because of the state's finance and personnel
      crises. While protection of its people remains the prerogative of the Haitian
      government, it is extremely limited in managing chemical exposure to
      environmental toxins, including aflatoxin and heavy metals. CONCLUSIONS: The
      cases of DEG and ackee fruit poisoning demonstrate that environmental exposures
      to chemicals have occurred in Haiti. Current low-level exposures to aflatoxin and
      heavy metals highlight the risk that large-scale poisonings can occur. While
      awareness of toxicological hazards in Haiti must be acknowledged more widely
      within the government and non-governmental sectors, the lessons of these
      exposures are relevant to all developing countries where the capacity to discern
      and manage toxicological risks is absent or not yet effective.

PMID- 24134534
TI  - Antidote removal during haemodialysis for massive acetaminophen overdose.
AB  - CONTEXT: Haemodialysis is sometimes used for patients with massive acetaminophen
      overdose when signs of "mitochondrial paralysis" (lactic acidosis, altered mental
      status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is
      debated, in part because the evidence base is weak and the endogenous clearance
      of acetaminophen is high. There is also concern because the antidote
      acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine
      concentrations during haemodialysis in three such cases. CASE DETAILS: Three
      adults each presented comatose and acidemic 10 to ~18 h after ingesting >
      1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum
      lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and
      initial acetaminophen concentrations were as high as 5980 MUM (900 MUg/mL). An
      intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8
      and ~18 h post ingestion, and additional doses were empirically administered
      during haemodialysis to compensate for possible antidote removal. A single run of
      3-4 h of haemodialysis removed 10-20 g of acetaminophen (48-80% of remaining body
      burden), reduced serum acetaminophen concentrations by 56-84% (total clearance
      3.4-7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination
      half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and
      corrected acidemia. Extraction ratios of acetylcysteine across the dialysis
      circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three
      patients recovered fully, and none developed coagulopathy or other signs of liver
      failure. DISCUSSION: When massive acetaminophen ingestion is accompanied by coma
      and lactic acidosis, emergency haemodialysis can result in rapid biochemical
      improvement. As expected, haemodialysis more than doubles the clearance of both
      acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely
      empirical, we recommend doubling the dose during haemodialysis, with an
      additional half-load when dialysis exceeds 6 h.

PMID- 24134535
TI  - Canadian poison control centres: preliminary assessment of their potential as a
      resource for public health surveillance.
AB  - CONTEXT: In the United States (US) and Europe, surveillance based on calls to
      poison control centres has identified new hazards and evolving exposure trends.
      In Canada, the value of poison control centre calls as a tool for health hazard
      surveillance is largely unrecognized. OBJECTIVES: This preliminary survey was
      undertaken to describe current operational characteristics and surveillance
      capacities at Canadian poison control centres and to determine potential for
      developing a Canadian poison control centre collaborative network. METHODS: A
      structured quantitative-qualitative survey was administered to medical directors
      and clinical supervisors at the five Canadian poison control centres between
      March and May, 2012. RESULTS: All five Canadian poison control centres operate
      24/7 with each serving more than one province/territory. Annual call volumes
      range from 10,000 to 58,000. Data analysis is limited to detection of previously
      unrecognized hazards and short-term event-based adverse health monitoring.
      Currently no centre maintains systematic ongoing collection, integration and
      analysis of data. Constraints on personnel, resources and funding were identified
      as barriers to increasing capacity to provide and analyse call data. CONCLUSIONS:
      The potential exists to use Canadian poison control data as a novel source of
      public health surveillance. That they serve as sentinels for new or unexpected
      exposure events, have real-time electronic call-record capacity and demonstrate
      an interest in developing and sharing their call-record information supports
      their integration into existing public health networks.

PMID- 24134536
TI  - Electrochemistry of acids on platinum. Application to the reduction of carbon
      dioxide in the presence of pyridinium ion in water.
AB  - A detailed cyclic voltammetric investigation of the reduction of moderately weak
      acids on platinum reveals that they are reduced in two steps: one involving the
      hydrated protons initially present at equilibrium and the second the reduction of
      the acid through its prior conversion into hydrated protons. The reduction of
      pyridinium ions (protonated pyridine) follows this reaction scheme as does any
      other acid of similar pK (e.g., acetic acid). Rather than being catalytically
      reduced, CO2 plays a similar role through its prior conversion to carbonic acid.
      No trace of methanol or formate could be detected upon preparative-scale
      electrolysis of CO2 on the same electrode in the presence of pyridinium ions. 

PMID- 24134537
TI  - Forward motility is essential for trypanosome infection in the tsetse fly.
AB  - African trypanosomes are flagellated protozoan parasites transmitted by the bite
      of tsetse flies and responsible for sleeping sickness in humans. Their complex
      development in the tsetse digestive tract requires several differentiation and
      migration steps that are thought to rely on trypanosome motility. We used a
      functional approach in vivo to demonstrate that motility impairment prevents
      trypanosomes from developing in their vector. Deletion of the outer dynein arm
      component DNAI1 results in strong motility defects but cells remain viable in
      culture. However, although these mutant trypanosomes could infect the tsetse fly
      midgut, they were neither able to reach the foregut nor able to differentiate
      into the next stage, thus failing to complete their parasite cycle. This is the
      first in vivo demonstration that trypanosome motility is essential for the
      accomplishment of the parasite cycle. 

PMID- 24134538
TI  - Linear and nonlinear optical susceptibilities and the hyperpolarizability of
      borate LiBaB9O15 single-crystal: theory and experiment.
AB  - The single-crystal borate LiBaB9O15 was synthesized by a high-temperature
      solution reaction and structurally determined by the single-crystal X-ray
      diffraction technique. It crystallizes in the noncentrosymmetric space group R3c
      and features a three-dimensional infinity3[B9O15]3- anionic framework, with
      infinite channels in which the Li+ and Ba2+ cations are located. The linear
      optical properties were investigated experimentally in terms of the absorption
      spectrum, which reveals an optical gap of 5.17 eV. In addition we have calculated
      the linear optical properties using state-of-the-art all-electron full potential
      linearized augmented plane wave method. The nonlinear optical susceptibilities,
      namely, the second harmonic generation and the hyperpolarizability of the single
      crystal borate LiBaB9O15 are calculated and evaluated at a static limit and at
      lambda = 1064 nm. The calculation shows there exists three second-order nonlinear
      optical susceptiblities tensors components. We present measurements of the IR
      spectra in the range 500-2000 cm-1, and the second harmonic generation was
      performed using a Quantel 15 ns Nd:YAG laser operating at 1064 nm.

PMID- 24134539
TI  - Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from
      the German Ablation Registry.
AB  - BACKGROUND: Catheter ablation is used extensively with curative intention in
      atrial fibrillation. Radiofrequency ablation has long been a standard of care,
      while cryoballoon technology has emerged as a feasible approach with promising
      results. Prospective multicenter registry data referring to both ablation
      technologies in AF ablation therapy are lacking. METHODS: Between January 2007
      and August 2011, a total of 3,775 consecutive patients with symptomatic
      paroxysmal AF who underwent PV ablation in their respective centers were
      enrolled. The cohort was divided into 2 groups according to the ablation energy
      source used: cryoballoon ablation (group 1, n = 905 [24.0%], median age 63 years,
      64.3% men) and RF ablation (group 2, n = 2870 [76.0%], median age 63 years, 62.7%
      men). Comorbidities and baseline clinical characteristics were similar in both
      groups. RESULTS: Acute success rate was similar in both groups (97.5% in cryo vs
      97.6% in RF; P = 0.81). Procedure times were similar, ablation and fluoroscopy
      times were higher in cryoballoon when compared to RF ablation. Overall
      complication rate was similar in cryo- (4.6%) and RF-ablation (4.6%; P = 1.0).
      Phrenic nerve palsy was more often in cryo versus RF ablation (2.1% in cryo vs
      0.0% in RF; P < 0.001). Other complications were more common in RF compared to
      cryoablation (4.6% in RF vs 2.7% in cryo; P < 0.05). CONCLUSION: RF ablation is
      the most widespread ablation method in Germany, but use of cryoballoon increased
      significantly. Procedure times were similar, but ablation and fluoroscopy times
      were longer in cryoballoon ablation. No significant differences were found in
      terms of acute success and overall complication rate.

PMID- 24134540
TI  - Evidence for Scgb1a1(+) cells in the generation of p63(+) cells in the damaged
      lung parenchyma.
AB  - Transformation-related protein 63-expressing (p63(+)) basal cells are confined to
      the trachea in the mouse lung. However, after influenza virus infection or
      bleomycin treatment, patches of p63(+) cells were observed in the damaged lung
      parenchyma. To address whether the newly induced p63(+) cells are derived from
      the p63(+) basal cells, we performed lineage tracing. In a keratin 5 promoter
      driven CreER system, although preexisting p63(+) basal cells were labeled by
      enhanced green fluorescent protein (EGFP) after tamoxifen treatment, none or only
      a small fraction (~ 15%) of the p63(+) patches was labeled by EGFP after
      bleomycin treatment or influenza virus infection, respectively. In contrast, >
      60% of p63(+) patches contained EGFP(+) cells in Scgb1a1-CreER transgenic system
      where club cells are labeled. Many p63(+) cells were found in bronchiole-like
      lumen structures with columnar cells at the lumen side. The columnar cells were
      positive for club cell marker Cyp2f2 and could be traced to the newly induced
      p63(+) cells. These results suggest that most of the newly induced p63(+) cells
      in the damaged parenchyma are likely derived from club cells rather than from
      p63(+) basal cells and that newly induced p63(+) cells may be involved in the
      regeneration of bronchioles. 

PMID- 24134541
TI  - SiC2 siligraphene and nanotubes: novel donor materials in excitonic solar cells.
AB  - In excitonic solar cells (XSC), power conversion efficiency (PCE) depends
      critically on the interface band alignment between donor and acceptor materials.
      Graphene or silicene is not suitable for donor materials due to their
      semimetallic features (zero band gaps); it is therefore highly desired to open an
      energy gap in graphene or silicene to extend their application in optoelectronic
      devices, especially in photovoltaics. In this paper, based on the global particle
      swarm optimization algorithm and the density functional theory methods, we
      predict a novel SiC2 siligraphene (g-SiC2) with a direct band gap of 1.09 eV
      showing infinite planar geometry, in which Si and C atoms adopt sp(2)
      hybridization and C atoms form delocalized 4 C-domains that are periodically
      separated by Si atoms. Such a g-SiC2 siligraphene (with a global minimum of
      energy) is 0.41 eV/atom lower and thermally stabler than the isomeric pt-SiC2
      silagraphene containing planar 4-fold coordinated silicon (3000 K vs 1000 K).
      Interestingly, the derivative (n, 0), (n, n) nanotubes (with diameters greater
      than 8.0 A) have band gaps about 1.09 eV, which are independent of the chirality
      and diameter. Besides, a series of g-SiC2/GaN bilayer and g-SiC2 nanotube/ZnO
      monolayer XSCs have been proposed, which exhibit considerably high PCEs in the
      range of 12-20%. 

PMID- 24134542
TI  - BaTiO3 integration with nanostructured epitaxial (100), (110), and (111)
      germanium for multifunctional devices.
AB  - Ferroelectric-germanium heterostructures have a strong potential for
      multifunctional devices. Germanium (Ge) is attractive due to its higher electron
      and hole mobilities while ferroelectric BaTiO3 is promising due to its high
      relative permittivity, which can make next-generation low-voltage and low-leakage
      metal-oxide semiconductor field-effect transistors. Here, we investigate the
      growth, structural, chemical, and band alignment properties of pulsed laser
      deposited BaTiO3 on epitaxial (100)Ge, (110)Ge, and (111)Ge layers. Cross
      sectional transmission electron microscopy micrographs show the amorphous nature
      of the BaTiO3 layer and also show a sharp heterointerface between BaTiO3 and Ge.
      The appearance of strong Pendellosung oscillation fringes from high-resolution X
      ray diffraction implies the presence of parallel and sharp heterointerfaces. The
      valence band offset relation of DeltaEV(100) >= DeltaEV(111) > DeltaEV(110) and
      the conduction band offset relation of DeltaE(C)(110) > DeltaE(C)(111) >=
      DeltaE(C)(100) on crystallographically oriented Ge offer significant advancement
      for designing new-generation ferroelectric-germanium-based multifunctional
      devices.

PMID- 24134543
TI  - The implementation and evaluation of an evidence-based statewide prehospital pain
      management protocol developed using the national prehospital evidence-based
      guideline model process for emergency medical services.
AB  - BACKGROUND: In 2008, the National Highway Traffic Safety Administration funded
      the development of a model process for the development and implementation of
      evidence-based guidelines (EBGs) for emergency medical services (EMS). We report
      on the implementation and evaluation of an evidence-based prehospital pain
      management protocol developed using this model process. METHODS: An evidence
      based protocol for prehospital management of pain resulting from injuries and
      burns was reviewed by the Protocol Review Committee (PRC) of the Maryland
      Institute for Emergency Medical Services Systems (MIEMSS). The PRC recommended
      revisions to the Maryland protocol that reflected recommendations in the EBG:
      weight-based dosing and repeat dosing of morphine. A training curriculum was
      developed and implemented using Maryland's online Learning Management System and
      successfully accessed by 3,941 paramedics and 15,969 BLS providers. Field
      providers submitted electronic patient care reports to the MIEMSS statewide
      prehospital database. Inclusion criteria were injured or burned patients
      transported by Maryland ambulances to Maryland hospitals whose electronic patient
      care records included data for level of EMS provider training during a 12-month
      preimplementation period and a 12-month postimplementation period from September
      2010 through March 2012. We compared the percentage of patients receiving pain
      scale assessments and morphine, as well as the dose of morphine administered and
      the use of naloxone as a rescue medication for opiate use, before and after the
      protocol change. RESULTS: No differences were seen in the percentage of patients
      who had a pain score documented or the percent of patients receiving morphine
      before and after the protocol change, but there was a significant increase in the
      total dose and dose in mg/kg administered per patient. During the
      postintervention phase, patients received an 18% higher total morphine dose and a
      14.9% greater mg/kg dose. CONCLUSIONS: We demonstrated that the implementation of
      a revised statewide prehospital pain management protocol based on an EBG
      developed using the National Prehospital Evidence-based Guideline Model Process
      was associated with an increase in dosing of narcotic pain medication consistent
      with that recommended by the EBG. No differences were seen in the percentage of
      patients receiving opiate analgesia or in the documentation of pain scores.

PMID- 24134544
TI  - Stability and magnetically induced heating behavior of lipid-coated Fe3O4
      nanoparticles.
AB  - Magnetic nanoparticles that are currently explored for various biomedical
      applications exhibit a high propensity to minimize total surface energy through
      aggregation. This study introduces a unique, thermoresponsive nanocomposite
      design demonstrating substantial colloidal stability of superparamagnetic Fe3O4
      nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating
      was accomplished in different buffer systems, pH 7.4, using an equimolar mixture
      of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and l-alpha
      dipalmitoylphosphatidyl glycerol (DPPG). Particle size and zeta potential were
      measured by dynamic laser light scattering. Heating behavior within an
      alternating magnetic field was compared between the commercial MFG-1000 magnetic
      field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic
      hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product
      quality of lipid-coated SPIONs was significantly dependent on the colloidal
      stability of uncoated SPIONs during the coating process. Greatest stability was
      achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 +/- 1.7 nm; zeta
      potential = -47.1 +/- 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG
      layer effectively reduced the impact of buffer components on particle
      aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained
      at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 +/- 13.9 nm; zeta
      potential = -19.1 +/- 2.3 mV). The configuration of the magnetic field generator
      significantly affected the heating properties of fabricated SPIONs. Heating rates
      of uncoated nanoparticles were substantially dependent on buffer composition but
      less influenced by particle concentration. In contrast, thermal behavior of lipid
      coated nanoparticles within an alternating magnetic field was less influenced by
      suspension vehicle but dramatically more sensitive to particle concentration.
      These results underline the advantages of lipid-coated SPIONs on colloidal
      stability without compromising magnetically induced hyperthermia properties.
      Since phospholipids are biocompatible, these unique lipid-coated Fe3O4
      nanoparticles offer exciting opportunities as thermoresponsive drug delivery
      carriers for targeted, stimulus-induced therapeutic interventions. PACS: 7550Mw;
      7575Cd; 8185Qr. 

PMID- 24134545
TI  - Fetal anemia as a signal of congenital syphilis.
AB  - An upsurge in syphilis has been observed almost everywhere over the past decade.
      The mother's clinical presentation is often uninformative. The diagnosis of
      maternal syphilis infection is most often based on serologic tests that allow
      early Extencilline treatment. Syphilis ultrasound findings are non-specific, and
      delay before treatment can be decisive for prognosis. Fetal anemia is a
      physiological consequence of severe infection. We confirmed that syphilis can be
      suggested non-invasively by MCA-PSV measurements in a context of ascitis or
      atypical hydrops in the absence of usual causes. It is therefore important to
      perform maternal TPHA/VDRL serology if fetal anemia is suspected. In association
      with Extencilline treatment, intra uterine transfusion can limit consequences of
      infection. Reduced fetal movements and non-reactive fetal heart rate may
      prefigure acute perinatal complications or stillbirth.

PMID- 24134546
TI  - Alkaline earth complexes of silylated aminopyridinato ligands: homoleptic
      compounds and heterobimetallic coordination polymers.
AB  - The synthesis and characterization of magnesium and calcium complexes of
      sterically demanding aminopyridinato ligands is reported. The reaction of the 2
      Me3SiNH-6-MeC5H3N (L(1)H), 2-MePh2SiNH-6-MeC5H3N (L(2)H), and 2-Me3SiNH-6-PhC5H3N
      (L(3)H) with KH in tetrahydrofuran (THF) yielded potassium salts L(1)K(thf)0.5
      (1), L(2)K (2), and L(3)K(thf)0.5 (3), which, through subsequent reaction with
      MgI2 and CaI2, afforded the homoleptic complexes (L)2Ae(thf)n [L = L(1), Ae = Mg,
      n = 1 (4); L = L(2), Ae = Mg, n = 0 (5); L = L(3), Ae = Mg, n = 0 (6); L = L(2),
      Ae = Ca, n = 2 (7)] and heterobimetallic calciates {[(L)3Ca]K}infinity [L = L(1)
      (8); L = L(2) (9)]. The solid state structure of 8 reveals a polymeric
      arrangement in which the calciate units are interlocked by bridging potassium
      ions. Metalation reactions between L(1)H or L(2)H and ((n)Bu)2Mg lead to the
      solvent-free compounds (L)2Mg [L = L(1) (10); L = L(2) (5)]. The bridged butyl
      mixed-metal complex [(L(1))Li(MU2-(n)Bu)Mg(L(1))]infinity (11) was also obtained
      via a cocomplexation reaction with (n)BuLi and ((n)Bu)2Mg. 11, which adopts a
      monodimensional polymeric array in the solid state, is a rare example of an alkyl
      bridged Li/Mg complex and the first complex to feature an unsupported bridging
      butyl interaction between two metals. Changing the cocomplexation reaction
      conditions, the order of reagents added to the reactions mixture, and with the
      use of a coordinating solvent (tetrahydrofuran) formed the magnesiate complex
      (L(1))3MgLi(thf) (12). 

PMID- 24134547
TI  - Value of a simple method to assess chronic rejection in renal allograft on
      electron microscopy.
AB  - Electron microscopy is a powerful tool for the assessment of complex lesions in
      nontumor renal pathology, however it is a time-consuming procedure. We evaluated
      a simple method to assess morphological signs of chronic rejection in renal
      allograft that seems to have prognostic significance.

PMID- 24134548
TI  - The effects of earlier income variation on mortality: an analysis of Norwegian
      register data.
AB  - Several studies have shown a positive relationship between mortality and episodes
      of income decline, unemployment, or poverty shortly before death or in the more
      distant past. Our objective was to analyse the mortality effects of earlier
      income changes more generally, net of the overall level. We used Norwegian
      register data that included individual histories of annual labour income and
      focused on mortality among men aged 50-69 in 1990-2002. Men in this age group
      who, during the preceding 15 years, had experienced at least two substantial
      falls in income as well as at least one substantial increase, or vice versa,
      experienced an excess mortality of 17 per cent. For men who experienced fewer
      changes, there were only weak indications of excess mortality. Variation
      dominated by falls in income did not have a more adverse effect than variation
      dominated by rises. 

PMID- 24134549
TI  - Ascertaining the suitability of aryl sulfonyl fluorides for [18F]radiochemistry
      applications: a systematic investigation using microfluidics.
AB  - Optimization of [(18)F]radiolabeling conditions and subsequent stability analysis
      in mobile phase, PBS buffer, and rat serum of 12 aryl sulfonyl chloride
      precursors with various substituents (electron-withdrawing groups, electron
      donating groups, increased steric bulk, heterocyclic) were performed using an
      Advion NanoTek Microfluidic Synthesis System. A comparison of radiochemical
      yields and reaction times for a microfluidics device versus a conventional
      reaction vessel is reported. [(18)F]Radiolabeling of sulfonyl chlorides in the
      presence of competing nucleophiles, H-bond donors, and water was also assessed
      and demonstrated the versatility and potential utility of [(18)F]sulfonyl
      fluorides as synthons for indirect radiolabeling. 

PMID- 24134550
TI  - Activin A is associated with impaired myocardial glucose metabolism and left
      ventricular remodeling in patients with uncomplicated type 2 diabetes.
AB  - BACKGROUND: Activin A released from epicardial adipose tissue has been linked to
      contractile dysfunction and insulin resistance in cardiomyocytes. This study
      investigated the role of activin A in clinical diabetic cardiomyopathy by
      assessing whether circulating activin A levels associate with cardiometabolic
      parameters in men with uncomplicated type 2 diabetes (T2D), and the effects of
      treatment with pioglitazone versus metformin on these associations. METHODS:
      Seventy-eight men with uncomplicated T2D and fourteen healthy men with comparable
      age were included, in this randomized, double-blind, active comparator
      intervention study. All T2D men were on glimipiride monotherapy, and randomized
      to a 24-week intervention with either pioglitazone or metformin. Cardiac
      dimensions and -function were measured using magnetic resonance imaging, whilst
      myocardial glucose metabolism (MMRglu) was determined using [18F]-2-fluoro-2
      deoxy-D-glucose positron emission tomography during a hyperinsulinemic-euglycemic
      clamp. RESULTS: Circulating activin A levels were comparable in T2D men and
      controls. Activin A levels were independently inversely associated with MMRglu,
      and positively with left ventricular mass/volume (LVMV)-ratio in T2D men.
      Intervention with metformin decreased activin A levels, whereas pioglitazone did
      not alter activin A levels. The changes in plasma activin A levels were not
      correlated with the changes in MMRglu following either pioglitazone or metformin
      treatment. A borderline significant correlation (p = 0.051) of changes in plasma
      activin A levels and changes in LVMV-ratio was observed after pioglitazone
      treatment. CONCLUSIONS: Circulating activin A levels are associated with impaired
      myocardial glucose metabolism and high LVMV-ratio in patients with uncomplicated
      T2D, reflecting a potential detrimental role in early human diabetic
      cardiomyopathy. TRIAL REGISTRATION NUMBER: Current Controlled Trials
      SRCTN53177482.

PMID- 24134551
TI  - Hyperventilation and exhaustion syndrome.
AB  - Chronic stress is among the most common diagnoses in Sweden, most commonly in the
      form of exhaustion syndrome (ICD-10 classification - F43.8). The majority of
      patients with this syndrome also have disturbed breathing (hyperventilation). The
      aim of this study was to investigate the association between hyperventilation and
      exhaustion syndrome. Thirty patients with exhaustion syndrome and 14 healthy
      subjects were evaluated with the Nijmegen Symptom Questionnaire (NQ). The
      participants completed questionnaires about exhaustion, mental state, sleep
      disturbance, pain and quality of life. The evaluation was repeated 4 weeks later,
      after half of the patients and healthy subjects had engaged in a therapy method
      called 'Grounding', a physical exercise inspired by African dance. The patients
      reported significantly higher levels of hyperventilation as compared to the
      healthy subjects. All patients' average score on NQ was 26.57 +/- 10.98, while
      that of the healthy subjects was 15.14 +/- 7.89 (t = -3.48, df = 42, p < 0.001).
      The NQ scores correlated strongly with two measures of exhaustion (Karolinska
      Exhaustion Scale KES r = 0.772, p < 0.01; Shirom Melamed Burnout Measure SMBM r =
      0.565, p < 0.01), mental status [Hospital Anxiety and Depression Score (HADS)
      depression r = 0.414, p < 0.01; HADS anxiety r = 0.627, p < 0.01], sleep
      disturbances (r = -0.514, p < 0.01), pain (r = -.370, p < 0.05) and poor well
      being (Medical Outcomes Survey Short Form 36 questionnaire- SR Health r = -0.529,
      p < 0.05). In the logistic regression analysis, the variance in the scores from
      NQ were explained to a high degree (R(2) = 0.752) by scores in KES and HADS. The
      brief Grounding training contributed to a near significant reduction in
      hyperventilation (F = 2.521, p < 0.124) and to significant reductions in
      exhaustion scores and scores of depression and anxiety. The conclusion is that
      hyperventilation is common in exhaustion syndrome patients and that it can be
      reduced by systematic physical therapy such as Grounding.

PMID- 24134552
TI  - Fetal heart rate variability during pregnancy, obtained from non-invasive
      electrocardiogram recordings.
AB  - OBJECTIVE: Non-invasive spectral analysis of fetal heart rate variability is a
      promising new field of fetal monitoring. To validate this method properly, we
      studied the relationship between gestational age and the influence of fetal rest
      activity state on spectral estimates of fetal heart rate variability. DESIGN:
      Prospective longitudinal study. SETTING: Tertiary care teaching hospital.
      POPULATION: Forty healthy women with an uneventful singleton pregnancy. METHODS:
      Non-invasive fetal electrocardiogram measurements via the maternal abdomen were
      performed at regular intervals between 14 and 40 weeks of gestation and processed
      to detect beat-to-beat fetal heart rate. Simultaneous ultrasound recordings were
      performed to assess fetal rest-activity state. MAIN OUTCOME MEASURES: Absolute
      and normalized power of fetal heart rate variability in the low (0.04-0.15 Hz)
      and high (0.4-1.5 Hz) frequency band were obtained, using Fourier Transform.
      RESULTS: 14% of all measurements and 3% of the total amount of abdominal data
      (330 segments) was usable for spectral analysis. During 21-30 weeks of gestation,
      a significant increase in absolute low and high frequency power was observed.
      During the active state near term, absolute and normalized low frequency power
      were significantly higher and normalized high frequency power was significantly
      lower compared with the quiet state. CONCLUSIONS: The observed increase in
      absolute spectral estimates in preterm fetuses was probably due to increased
      sympathetic and parasympathetic modulation and might be a sign of autonomic
      development. Further improvements in signal processing are needed before this new
      method of fetal monitoring can be introduced in clinical practice.

PMID- 24134553
TI  - Mass spectrometry imaging for dissecting steroid intracrinology within target
      tissues.
AB  - Steroid concentrations within tissues are modulated by intracellular enzymes.
      Such "steroid intracrinology" influences hormone-dependent cancers and obesity
      and provides targets for pharmacological inhibition. However, no high resolution
      methods exist to quantify steroids within target tissues. We developed mass
      spectrometry imaging (MSI), combining matrix assisted laser desorption ionization
      with on-tissue derivatization with Girard T and Fourier transform ion cyclotron
      resonance mass spectrometry, to quantify substrate and product (11
      dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme
      11beta-HSD1. Regional steroid distribution was imaged at 150-200 MUm resolution
      in rat adrenal gland and mouse brain sections and confirmed with collision
      induced dissociation/liquid extraction surface analysis. In brains of mice with
      11beta-HSD1 deficiency or inhibition, MSI quantified changes in subregional
      corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and
      accumulation of the alternative 11beta-HSD1 substrate, 7-ketocholesterol. MSI
      data correlated well with LC-MS/MS in whole brain homogenates. MSI with
      derivatization is a powerful new tool to investigate steroid biology within
      tissues. 

PMID- 24134554
TI  - The meaning of self-care in persons with cervical spinal cord injury in Japan: a
      qualitative study.
AB  - BACKGROUND: Professionals in Japan tend to regard the individual contexts of
      persons with spinal cord injury (SCI) as the cause of their passive participation
      in self-care activities or self-management. However, the meaning of self-care
      involves variables that interrelate with sociocultural factors. Thus, it is
      necessary to uncover its meaning in the perceptions of persons with cervical
      spinal cord injury (CSCI) in order not only to implement better rehabilitation
      but also to understand the sociocultural constraints that determine the injured
      person's attitudes to self-care and long-term health outcomes. METHODS: Semi
      structured interviews with 29 CSCI participants from fourteen municipalities of
      Osaka, Hyogo, and Ehime prefectures were conducted. Participants contributed
      diverse perspectives on rehabilitation, lay-professional and family
      relationships, health promotion, and body conceptions. Interviews were recorded,
      transcribed and analyzed using the grounded theory approach to inter-relate
      categories and to develop theoretical constructions. RESULTS: Four main themes
      emerged from the data: rehabilitation for independence in ADLs; detachment from
      the body and self; embodiment; and self-management. From the participants' point
      of view, rehabilitation programs in Japan aim at improving body functions for ADL
      performance, but provide little health education. These rehabilitation values
      might hinder some participants from developing self-esteem for their bodies.
      Moreover, socially-shaped family caregivers' active engagement in the
      participants' self-care allowed many participants to entirely rely on them for
      care. Through embodiment, participants found that self-care was not merely a
      means of independence in ADLs but also of self-management to enhance health and
      well-being, requiring collaborative relationships with caregivers. CONCLUSION:
      Personal factors such as low motivation for self-care might be in part a
      reflection of social expectations of dependence for persons with CSCI. However,
      the shift in the meaning of self-care from ADLs to self-management implies more
      active participation in health care needs, shaped through social exchanges. Not
      only personal factors but also sociocultural factors influence the injured
      person's valuation of self-care. There is a need for further research to better
      understand sociocultural influences on illness behaviors among persons with CSCI,
      so that clinical and community practice can develop accordingly.

PMID- 24134555
TI  - Right ventricular ejection efficiency: a new echocardiographic measure of
      mechanical performance in chronic pulmonary hypertension.
AB  - BACKGROUND: The severity of pulmonary vascular resistance (PVR) is known to be a
      critical determinant of right ventricular (RV) systolic function; this
      relationship remains poorly characterized. We therefore, designed a study to
      examine the relationship that exists between echocardiographically measured PVR
      and maximal tricuspid annular plane systolic excursion (TAPSE) to gain some
      insight regarding RV ejection efficiency (RVEe) in patients with chronic
      pulmonary hypertension (cPH). METHODS: Standard echocardiographic measures of RV
      size and systolic performance were recorded from 95 patients (age 54 +/- 15 years
      and pulmonary artery systolic pressures [PASP] that range from 20 to 125 mmHg).
      For this study, RVEe was defined as TAPSE/Echocardiographic PVR. RESULTS: A
      strong negative correlation (R(2) = -0.51, P < 0.001) was seen between TAPSE and
      PASP; however, a power curve trend line fit the relationship between RVEe and
      PASP (R(2) = 0.77; P < 0.01). In a multiple regression analysis, abnormal
      pulmonary pressures were better identified when RVEe (P < 0.0001) was used.
      CONCLUSIONS: Based on these results, it appears that measurement of RVEe might be
      extremely useful for the assessment of RV mechanics and plasticity. The power
      curve relationship clearly demonstrates that minimal changes in PASP (up to 50
      mmHg) result in dramatic reductions in RVEe. A steady decline in RVEe, though at
      a lower rate, continues to occur with increasing PASP. Additional studies are
      required using RVEe into a functional RV imaging algorithm and determine if RVEe
      correlates with development of symptoms, response to therapy and overall clinical
      outcomes.

PMID- 24134556
TI  - The Eagle-like effect of echinocandins: what's in a name?
AB  - Despite several years of research, a lot of questions remain about the
      paradoxical attenuation of echinocandin activity against Candida and Aspergillus
      species at certain drug concentrations above the MIC values, the so-called
      paradoxical growth effect or Eagle-like effect. Although this phenomenon has been
      observed in several in vitro studies, confirming in vivo data are scarce. The
      clinical relevance remains unknown, although more and more data suggest that the
      clinical impact of this phenomenon might be heavily overrated. Detailed knowledge
      about the mechanisms responsible for this phenomenon and further research about
      the presence of the effect in the human body is necessary to decide whether the
      paradoxical growth effect of echinocandins can really interfere with an adequate
      treatment of invasive fungal diseases in clinical practice. 

PMID- 24134557
TI  - Genetic heterogeneity of within-family variance of body weight in Atlantic salmon
      (Salmo salar).
AB  - BACKGROUND: Canalization is defined as the stability of a genotype against minor
      variations in both environment and genetics. Genetic variation in degree of
      canalization causes heterogeneity of within-family variance. The aims of this
      study are twofold: (1) quantify genetic heterogeneity of (within-family) residual
      variance in Atlantic salmon and (2) test whether the observed heterogeneity of
      (within-family) residual variance can be explained by simple scaling effects.
      RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical
      generalized linear model (DHGLM) revealed substantial heterogeneity of within
      family variance. The 95% prediction interval for within-family variance ranged
      from ~0.4 to 1.2 kg2, implying that the within-family variance of the most
      extreme high families is expected to be approximately three times larger than the
      extreme low families. For cross-sectional data, DHGLM with an animal mean sub
      model resulted in severe bias, while a corresponding sire-dam model was
      appropriate. Heterogeneity of variance was not sensitive to Box-Cox
      transformations of phenotypes, which implies that heterogeneity of variance
      exists beyond what would be expected from simple scaling effects. CONCLUSIONS:
      Substantial heterogeneity of within-family variance was found for body weight in
      Atlantic salmon. A tendency towards higher variance with higher means (scaling
      effects) was observed, but heterogeneity of within-family variance existed beyond
      what could be explained by simple scaling effects. For cross-sectional data,
      using the animal mean sub-model in the DHGLM resulted in biased estimates of
      variance components, which differed substantially both from a standard linear
      mean animal model and a sire-dam DHGLM model. Although genetic differences in
      canalization were observed, selection for increased canalization is difficult,
      because there is limited individual information for the variance sub-model,
      especially when based on cross-sectional data. Furthermore, potential macro
      environmental changes (diet, climatic region, etc.) may make genetic
      heterogeneity of variance a less stable trait over time and space.

PMID- 24134558
TI  - Therapy of pathological scars.
AB  - The various clinical manifestations of scarring are an important topic for
      physicians in many disciplines. The prevention of excessive scarring is more
      successful than the treatment afterwards. Multiple options exist for prevention,
      wound repair modulation, and treatment of scars. This publication includes an
      overview of the pathogenesis, clinical classification, documentation, prevention,
      and invasive and non-invasive therapy options. 

PMID- 24134559
TI  - Shape features of epileptic spikes are a marker of epileptogenesis in mice.
AB  - PURPOSE: To identify reliable biomarkers for quantitatively assessing the
      development of epilepsy in brain. METHODS: In a kainate mouse model of temporal
      lobe epilepsy, we performed long-term video-electroencephalography (EEG)
      monitoring (several weeks) of freely moving animals, from kainic acid injection
      to chronic epileptic stage. Using signal processing techniques, we automatically
      detected single epileptic spikes (ESs), and we quantified the evolution of shape
      features during the epileptogenesis process. Using a computational model of
      hippocampal activity (neuronal population level), we investigated excitatory
      related and inhibitory-related parameters involved in morphologic changes of ESs.
      KEY FINDINGS: The frequency of ESs increases during epileptogenesis. Regarding
      shape features, we found that both the initial spike component and the wave
      component of opposite polarity of ESs gradually increase during epileptogenesis.
      These very specific alterations of the shape of ESs were reproduced in a
      computational physiologically relevant neuronal population model. Using this
      model, we disclosed some key parameters (related to glutamatergic and gamma
      aminobutyric acid [GABA]ergic synaptic transmission) that explain the shape
      features of simulated ESs. Of interest, the model predicted that the decrease of
      GABAergic inhibition is responsible for the increase of the wave component of
      ESs. This prediction (at first sight counterintuitive) was verified in both in
      vivo and in vitro experiments. Finally, from aforementioned electrophysiologic
      features, we devised a novel and easily computable index (wave area/spike
      amplitude ratio) indicative of the progression of the disease (early vs. late
      stage). SIGNIFICANCE: Results suggest that dendritic inhibition in hippocampal
      circuits undertake dramatic changes over the latent period. These changes are
      responsible for observed modifications in the shape of ESs recorded in local
      field potential (LFP) signals. The proposed index may constitute a biomarker of
      epileptogenesis.

PMID- 24134560
TI  - Histoid leprosy with mycobacterial keratinous bullets after possible
      transepidermal elimination of bacilli.

PMID- 24134561
TI  - Mizoribine selectively attenuates monocyte chemoattractant protein-1 production
      in cultured human glomerular mesangial cell: a possible benefit of its use in the
      treatment of lupus nephritis.
AB  - AIM: Mizoribine (MZR) is a selective inhibitor of the inosine monophosphate
      dehydrogenase - a key enzyme in the de novo pathway of guanine nucleotides - that
      was developed in Japan. Besides its immunosuppressive effects, MZR has recently
      been reported to suppress the progression of histologic chronicity via
      suppression of macrophage infiltration of the interstitium in selected patients
      with lupus nephritis. METHODS: We examine the direct effect of MZR in human
      mesangial cells on the expression of functional molecules including monocyte
      chemoattractants in cultured human mesangial cells (MCs) treated with
      polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA,
      that makes 'pseudoviral' infection, and analyzed the expression of target
      molecules by reverse transcriptase-polymerase chain reaction and Western
      blotting. Thereafter, the effect of MZR on the expressions was examined. RESULTS:
      Pretreatment of cells with MZR partially, but significantly, attenuates the
      expression of monocyte chemoattractant protein (MCP)-1 mRNA and protein, whereas
      the poly IC-induced expressions for the other functional molecules, such as CCL5,
      fractalkine and IL-8 were not influenced by MZR treatment. On the other hand,
      pretreatment of cells with tacrolimus did not suppress the expression of MCP-1
      mRNA. CONCLUSION: Mizoribine itself selectively attenuated the expression of MCP
      1 both mRNA and protein levels in MCs treated with poly IC; that is, a possible
      model of 'pseudoviral' infection, which may be involved in the pathogenesis of
      lupus nephritis.

PMID- 24134562
TI  - Colonic decompression and direct intraluminal medical therapy for Clostridium
      difficile-associated megacolon using a tube placed endoscopically in the proximal
      colon.
AB  - AIM: Urgent colectomy for severe Clostridium difficile infection can be
      associated with increased morbidity and mortality. We aimed to use endoscopic
      methods for treatment. METHOD: We describe a technique of placing an intracolonic
      tube facilitating decompression and direct delivery of vancomycin to the proximal
      colon along with enemas on a regular and frequent basis that may not be possible
      with vancomycin enemas alone. RESULTS: Successful resolution of the C. difficile
      infection and avoidance of surgery. CONCLUSION: While further long-term
      evaluation is required, our initial results have shown it to be effective in
      treating select patients with recalcitrant Clostridium difficile-associated
      megacolon.

PMID- 24134563
TI  - The effect of HPMC particle size on the drug release rate and the percolation
      threshold in extended-release mini-tablets.
AB  - The particle size of HPMC is a critical factor that can influence drug release
      rate from hydrophilic matrix systems. Percolation theory is a statistical tool
      which is used to study the disorder of particles in a lattice of a sample. The
      percolation threshold is the point at which a component is dominant in a cluster
      resulting in significant changes in drug release rates. Mini-tablets are compact
      dosage forms of 1.5-4 mm diameter, which have potential benefits in the delivery
      of drug to some patient groups such as pediatrics. In this study, the effect of
      HPMC particle size on hydrocortisone release and its associated percolation
      threshold for mini-tablets and tablets was assessed. For both mini-tablets and
      tablets, large polymer particles reduced tensile strength, but increased the drug
      release rate and the percolation threshold. Upon hydration, compacts with 45-125
      MUm HPMC particles formed a strong gel layer with low porosity, reducing
      hydrocortisone release rates. In comparison, faster drug release rates were
      obtained when 125-355 um HPMC particles were used, due to the greater pore sizes
      that resulted in the formation of a weaker gel. Using 125-355 um HPMC particles
      increased the percolation threshold for tablets and to a greater extent for mini
      tablets. This work has demonstrated the importance of HPMC particle size in ER
      matrices, the effects of which are even more obvious for mini-tablets.

PMID- 24134564
TI  - A study of photostability and compatibility of the anti-chagas drug Benznidazole
      with pharmaceutics excipients.
AB  - Abstract Context: Benznidazole (BNZ) is an antiparasitic with trypanocidal
      properties for the etiological treatment of Chagas disease since 1973. Monitoring
      the stability of this drug is one of the most effective methods of assessment,
      forecasting and prevention of problems related to quality product. OBJECTIVE: To
      investigate the direct and indirect photodegradation of BNZ and to evaluate the
      interference of the excipients used in the forms dosage solid as well as to shed
      light on the chemical structure of the degradation products obtained. MATERIALS
      AND METHODS: To perform this work we adopted the "ICH Harmonised Tripartite
      Guideline: Photostability Testing of New Drug Substances and Products Q1B"
      (Guideline Q1B). We used benzonidazole (BNZ) (N-benzil-2-(2-nitroimidazol-1-il)
      acetamide) (LAFEPE(r), Recife, Brazil) and various excipients; beyond high
      performance liquid chromatography (HPLC), differential scanning calorimetry
      (DSC), infrared spectroscopy (IR) and mass spectrometry/mass spectrometry
      (MS/MS). The indirect photodegradation of BNZ was carried out using physical
      mixtures with 13 pharmaceutical excipients commonly used in the preparation of
      solid dosage forms. RESULTS: HPLC and MS/MS techniques were selected for the
      identification of two photoproducts (PPs) and photoreactions found in direct and
      indirect tests with the microcrystalline cellulose, considered a critical
      excipient. DISCUSSION: Despite variations in the infrared spectrometry,
      differential scanning calorimetry and differential thermogravimetry curves, these
      techniques are not conclusive since the study of photodegradation of the drug
      caused decay of 30%, according to the ICH. CONCLUSIONS: The results show that BNZ
      only undergoes direct photodegradation, since no new PPs were found for a
      combination of the drug and excipients.

PMID- 24134565
TI  - Thermoresponsive magnetic nanoparticles for seawater desalination.
AB  - Thermoresponsive magnetic nanoparticles (MNPs) as a class of smart materials that
      respond to a change in temperature may by used as a draw solute to extract water
      from brackish or seawater by forward osmosis (FO). A distinct advantage is the
      efficient regeneration of the draw solute and the recovery of water via heat
      facilitated magnetic separation. However, the osmotic pressure attained by this
      type of draw solution is too low to counteract that of seawater. In this work, we
      have designed a FO draw solution based on multifunctional Fe3O4 nanoparticles
      grafted with copolymer poly(sodium styrene-4-sulfonate)-co-poly(N
      isopropylacrylamide) (PSSS-PNIPAM). The resulting regenerable draw solution shows
      high osmotic pressure for seawater desalination. This is enabled by three
      essential functional components integrated within the nanostructure: (i) a Fe3O4
      core that allows magnetic separation of the nanoparticles from the solvent, (ii)
      a thermoresponsive polymer, PNIPAM, that enables reversible clustering of the
      particles for further improved magnetic capturing at a temperature above its low
      critical solution temperature (LCST), and (iii) a polyelectrolyte, PSSS, that
      provides an osmotic pressure that is well above that of seawater. 

PMID- 24134566
TI  - Glucose-6-phosphate dehydrogenase deficiency in Italian blood donors: prevalence
      and molecular defect characterization.
AB  - BACKGROUND: In the countries with high G6PD deficiency prevalence, blood donors
      are not routinely screened for this genetic defect. G6PD deficiency is often
      asymptomatic, blood donors may be carriers of the deficiency without being aware
      of it. The aim of the study was to evaluate the prevalence of G6PD deficiency
      among the Italian blood donors. DESIGN AND METHODS: From October 2009 to April
      2011, 3004 blood donors from a large hospital transfusion centre were screened
      for G6PD deficiency using differential pH-metry and the characterization of G6PD
      mutations was performed on G6PD-deficient subjects. The haematological features
      of G6PD-deficient and normal donors were also compared. RESULTS: Thirty-three
      subjects (25 men and 8 women) with low G6PD activity were identified,
      corresponding to 1.1% of the examined blood donor population. The frequencies of
      class II severe alleles (Mediterranean, Valladolid, Chatham and Cassano) and
      class III mild alleles (Seattle, A- and Neapolis) were 48% and 43%, respectively.
      The haematological parameters of G6PD- donors were within normal range; however,
      the comparison between normal and G6PD- class II donors showed significant
      differences. CONCLUSION: In Italy, the presence of blood donors with G6PD
      deficiency is not a rare event and the class II severe variants are frequent. The
      identification of G6PD-deficient donors and the characterization of the molecular
      variants would prevent the use of G6PD-deficient RBC units when the haemolytic
      complications could be relevant especially for high risk patients as premature
      infants and neonates and patients with sickle cell disease submitted to multiple
      transfusions.

PMID- 24134567
TI  - Modulated fluorescence of colloidal quantum dots embedded in a porous alumina
      membrane.
AB  - The fluorescence spectrum of CdSe core-CdS/ZnS shell colloidal quantum dots (QDs)
      embedded in porous alumina membrane was studied. Small peaks, superimposed on the
      principal QD fluorescence spectrum, were observed. Finite-difference time-domain
      simulation indicates that the QD point radiation emitting from within the
      membrane is strongly modulated by the photonic band structure introduced by the
      membrane pores, leading to the observed fine spectral features. Moreover, the
      principal QD fluorescence peak red-shifted when the optical excitation power was
      increased, which is attributed to QD material heating due to emitted phonons when
      the photoexcited electron and hole relax nonradiatively from high-energy states
      to the ground exciton state before fluorescence. 

PMID- 24134569
TI  - Study shines spotlight on neutering: assumptions about a mainstay of companion
      animal practice are called into question.

PMID- 24134570
TI  - Prazosin in cats with urethral obstruction.

PMID- 24134571
TI  - Concerns about extralabel fluoroquinolone use in food-producing animals.

PMID- 24134572
TI  - A strategic approach to workforce dynamics requires collaboration and sound data.

PMID- 24134573
TI  - What is your diagnosis? Pyelonephritis in a dog.

PMID- 24134574
TI  - What is your diagnosis? Disseminated histiocytic sarcoma.

PMID- 24134575
TI  - ECG of the month. Accelerated idioventricular rhythm during anesthesia.

PMID- 24134576
TI  - Pathology in practice. Marked leukocytosis as a result of end-stage bacteremia or
      septicemia in a diamond python.

PMID- 24134577
TI  - Compendium of measures to prevent disease associated with animals in public
      settings, 2013.

PMID- 24134578
TI  - A randomized controlled trial of the efficacy of autologous platelet therapy for
      the treatment of osteoarthritis in dogs.
AB  - OBJECTIVE: To determine efficacy of a single intra-articular injection of an
      autologous platelet concentrate for treatment of osteoarthritis in dogs. DESIGN:
      Randomized, controlled, 2-center clinical trial. ANIMALS: 20 client-owned dogs
      with osteoarthritis involving a single joint. PROCEDURES: Dogs were randomly
      assigned to a treatment or control group. In all dogs, severity of lameness and
      pain was scored by owners with the Hudson visual analog scale and the University
      of Pennsylvania Canine Brief Pain Inventory, respectively, and peak vertical
      force (PVF) was determined with a force platform. Dogs in the treatment group
      were then sedated, and a blood sample (55 mL) was obtained. Platelets were
      recovered by means of a point-of-use filter and injected intra-articularly within
      30 minutes. Control dogs were sedated and given an intra-articular injection of
      saline (0.9% NaCl) solution. Assessments were repeated 12 weeks after injection
      of platelets or saline solution. RESULTS: Dogs weighed between 18.3 and 63.9 kg
      (40.3 and 140.6 lb) and ranged from 1.5 to 8 years old. For control dogs,
      lameness scores, pain scores, and PVF at week 12 were not significantly different
      from pretreatment values. In contrast, for dogs that received platelet
      injections, lameness scores (55% decrease in median score), pain scores (53%
      decrease in median score), and PVF (12% increase in mean PVF) were significantly
      improved after 12 weeks, compared with pretreatment values. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that a single intra-articular injection of
      autologous platelets resulted in significant improvements at 12 weeks in dogs
      with osteoarthritis involving a single joint.

PMID- 24134580
TI  - Prevalence of uveal cysts and pigmentary uveitis in Golden Retrievers in three
      Midwestern states.
AB  - OBJECTIVE: To determine the prevalence of uveal cysts and pigmentary uveitis (PU)
      in Golden Retrievers in 3 Midwestern states. DESIGN: Prospective cross-sectional
      study. ANIMALS: 164 American Kennel Club-registered Golden Retrievers in the
      states of Illinois, Indiana, and Michigan. PROCEDURES: For all dogs,
      biomicroscopic and binocular indirect ophthalmoscopic examinations of both eyes
      were performed after pupillary dilation. A finding of pigment deposition in a
      radial pattern or in zones on the anterior aspect of the lens capsule of 1 or
      both eyes was required for a diagnosis of PU. RESULTS: Eighty of the 328 (24.4%)
      eyes and 57 of the 164 (34.8%) dogs had visible uveal cysts. Of those 80 eyes
      with cysts, 41 (51.3%) had a single cyst located nasally and posterior to the
      iris, 33 (41.3%) had multiple uveal cysts, and 6 (75%) had a single, free
      floating cyst. A diagnosis of PU was made for 9 (5.5%) dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Prevalences of uveal cysts (34.3%) and PU (5.5%) in the
      examined Golden Retrievers were both higher than prevalences reported previously
      (5.4% for uveal cysts and 1.5% for PU) in the Canine Eye Registry Foundation's
      2009 All-Breeds Report. Study findings have indicated that PU is not a rare
      condition and should be considered as a differential diagnosis for Golden
      Retrievers with ocular disease.

PMID- 24134581
TI  - Evaluation of routine hematology profile results and fructosamine, thyroxine,
      insulin, and proinsulin concentrations in lean, overweight, obese, and diabetic
      cats.
AB  - OBJECTIVE: To compare results of hematologic testing in nondiabetic and diabetic
      cats to identify possible indicators of alterations in long-term glucose control.
      DESIGN: Cross-sectional study. ANIMALS: 117 client-owned cats (76 nondiabetic
      cats [25 with normal body condition, 27 overweight, and 24 obese] and 41 naive [n
      = 21] and treated [20] diabetic cats). PROCEDURES: Signalment and medical
      history, including data on feeding practices, were collected. A body condition
      score was assigned, and feline body mass index was calculated. Complete blood
      counts and serum biochemical analyses, including determination of fructosamine,
      thyroxine, insulin, and proinsulin concentrations, were performed. Urine samples
      were obtained and analyzed. RESULTS: Glucose and fructosamine concentrations were
      significantly higher in the naive and treated diabetic cats than in the
      nondiabetic cats. Insulin and proinsulin concentrations were highest in the obese
      cats but had great individual variation. Few other variables were significantly
      different among cat groups. Most cats, even when obese or diabetic, had unlimited
      access to food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that cats
      at risk of developing diabetes (ie, overweight and obese cats) could not be
      distinguished from cats with a normal body condition on the basis of results of
      isolated hematologic testing. A longitudinal study is indicated to follow
      nondiabetic cats over a period of several years to identify those that eventually
      develop diabetes. Findings also suggested that dietary education of cat owners
      might be inadequate.

PMID- 24134582
TI  - Perianesthetic complications in dogs undergoing magnetic resonance imaging of the
      brain for suspected intracranial disease.
AB  - OBJECTIVE: To evaluate the occurrence of perianesthetic complications in dogs
      undergoing MRI for suspected intracranial disease and identify risk factors
      associated with observed complications. DESIGN: Retrospective case-control study.
      ANIMALS: 238 client-owned dogs undergoing MRI of the brain. PROCEDURES:
      Signalment, clinical signs, neurologic examination findings, presumptive
      diagnosis, anesthesia-related variables, whether CSF was collected and CSF
      analysis results, severe perianesthetic complications (need for a ventilator
      following anesthesia or perianesthetic death), and anesthetic recovery time were
      recorded. Selected factors were compared between dogs with and without
      intracranial lesions and dogs with and without perianesthetic complications
      (including severe complications and prolonged anesthetic recovery [> 20 minutes
      from the end of anesthesia to extubation]). RESULTS: 3 of 149 (2%) dogs with and
      0 of 89 dogs without intracranial lesions required ventilation following
      anesthesia; the difference was nonsignificant. Recovery time was significantly
      longer in dogs with (median, 15 minutes) than in dogs without (10 minutes)
      intracranial lesions. Abnormal mentation prior to anesthesia was the only
      clinical sign that differed significantly between dogs with (15/26 [58%]) and
      without (70/212 [33%]) perianesthetic complications. A significantly larger
      proportion of dogs with perianesthetic complications had intracranial masses
      (13/26 [50%]), compared with dogs without these complications (56/212 [26%]).
      CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with complications were more likely to
      have had intracranial lesions than were dogs without complications, but few dogs
      had severe complications. Abnormal mentation was more common in dogs with than in
      dogs without complications. Prospective studies to further evaluate
      perianesthetic risk factors and procedures for improving outcomes in these
      patients are warranted.

PMID- 24134583
TI  - Clinicopathologic and atypical features of naturally occurring leptospirosis in
      dogs: 51 cases (2000-2010).
AB  - OBJECTIVE: To determine clinicopathologic features, percentage of atypical
      abnormalities, antibody titers against Leptospira serogroups, and importance of
      convalescent titers in dogs with leptospirosis. DESIGN: Retrospective case
      series. ANIMALS: 51 dogs with leptospirosis. PROCEDURES: Criteria for inclusion
      were at least 1 positive microscopic agglutination test (MAT) result (titer >=
      1:1,600 in vaccinated dogs, titer >= 1:800 in nonvaccinated dogs, or >= 4-fold
      increase in convalescent titer), a complete medical record (including
      leptospirosis vaccination date, reason for initial evaluation, and CBC, serum
      biochemical analysis, and urinalysis results), and clinical signs or laboratory
      findings consistent with leptospirosis. RESULTS: Initial clinical signs, temporal
      distribution, and signalment were similar to previous reports. Convalescent MAT
      titers were necessary for diagnosis in 45% of cases. Atypical abnormalities
      included radiographic evidence of pulmonary disease in 10 of 23 dogs and hepatic
      involvement alone in 7 of 51 dogs. Other abnormalities included proteinuria in 34
      of 51 dogs, thrombocytopenia in 26 of 51, coagulopathy in 7 of 24 dogs,
      hypoalbuminemia in 14 of 51 dogs, and glucosuria in 9 of 51 dogs. Significant
      associations were found between antibodies against serogroup Grippotyphosa and
      renal involvement and serogroup Icterohaemorrhagiae and hepatic involvement.
      CONCLUSIONS AND CLINICAL RELEVANCE: Increased awareness of atypical abnormalities
      may decrease misdiagnosis of leptospirosis in dogs. Results of concurrent
      infectious disease testing should be interpreted with caution; misdiagnosis of
      leptospirosis could pose a public health risk. Convalescent titers were necessary
      to identify infection when acute testing results were negative. Further research
      is needed to determine the true associations between antibodies against
      identified serogroups and clinical features.

PMID- 24134584
TI  - Laparoscopic removal of a bladder urolith in a standing horse.
AB  - CASE DESCRIPTION: An 11-year-old Arabian gelding was evaluated for hematuria,
      stranguria, and pollakiuria that had been observed for 1 week. CLINICAL FINDINGS:
      Transrectal palpation revealed a 5-cm firm round mass in the urinary bladder.
      Cystoscopy and transrectal ultrasonography confirmed the diagnosis of urinary
      bladder urolithiasis. TREATMENT AND OUTCOME: A multiportal transparalumbar fossa
      laparoscopic approach was selected for cystotomy and urolith removal. Cystotomy
      and urolith removal was performed with sedation and local anesthesia with the
      horse standing. No perioperative complications were observed. Urination returned
      to normal 5 days after surgery. The horse returned to its previous level of
      activity at 3 weeks after surgery. CLINICAL RELEVANCE: Findings suggested that
      minimally invasive transparalumbar fossa laparoscopic approach can be
      successfully used for cystotomy and urolith extraction in standing horses; this
      avoids the disadvantages of conventional laparocystotomy for removal of large
      uroliths in male equids and the potential complications of general anesthesia and
      recovery. The technique provided excellent viewing and access to the bladder,
      permitting extraction of the urolith and secure closure of the cystotomy with
      minimal tension and tissue trauma to the bladder.

PMID- 24134585
TI  - Association between beta-hydroxybutyrate concentration at surgery for correction
      of left-displaced abomasum in dairy cows and removal from the herd after surgery.
AB  - OBJECTIVE: To estimate the sensitivity, specificity, likelihood ratios, and
      predictive values of blood beta-hydroxybutyrate (BHB) concentrations in dairy
      cows immediately prior to surgical correction of left-displaced abomasum (LDA)
      for determining associations between BHB concentration and removal from the herd
      <= 30 days after surgery and to evaluate postsurgical risk of removal for cows
      with the BHB concentration that had highest sensitivity and specificity for
      predicting this outcome. DESIGN: Prospective cohort study. ANIMALS: 136 dairy
      cows with LDA diagnosed between 5 and 30 days in lactation (ie, days in milk).
      PROCEDURES: Blood BHB concentration was measured immediately prior to surgery.
      All cows underwent surgical correction of LDA while standing. Follow-up
      information was obtained >= 30 days after surgery. Receiver operating
      characteristic curves were used to estimate a critical threshold value for BHB
      concentration that was associated with removal from the herd, and this value was
      used in Poisson regression to estimate risk ratio for the same outcome. RESULTS:
      While controlling for parity in the model, cows with a BHB concentration < 1.2
      mmol/L at the time of LDA surgery were 2.5 times as likely (95% confidence
      interval, 1.3 to 5.0) to be removed from the herd <= 30 days after surgery,
      compared with cows that had a BHB concentration >= 1.2 mmol/L. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that blood BHB concentration in dairy cows
      undergoing surgical correction of LDA may potentially be a useful prognostic
      indicator for the likelihood of removal from the herd <= 30 days after surgery.
      Further research is needed to evaluate other risk factors that may be associated
      with this outcome.

PMID- 24134586
TI  - Factors affecting use of veterinarians by small-scale food animal operations.
AB  - OBJECTIVE: To identify factors associated with use of a veterinarian by small
      scale food animal operations. DESIGN: Cross-sectional descriptive survey. SAMPLE:
      16,000 small-scale farm or ranch operations in all 50 states. PROCEDURES: Surveys
      were conducted via mail or telephone during 2011 for small-scale operations
      (gross annual agricultural sales between $10,000 and $499,999) in which an animal
      or animal product comprised the highest percentage of annual sales. RESULTS:
      8,186 (51.2%) operations responded to the survey; 7,849 surveys met the inclusion
      criteria. For 6,511 (83.0%) operations, beef cattle were the primary animal
      species. An estimated 82.1% of operations (95% confidence interval [CI], 81.1% to
      83.0%) had a veterinarian available <= 29 miles away; 1.4% (95% CI, 1.2% to 1.7%)
      did not have a veterinarian available within 100 miles of the operation.
      Operations for which the nearest veterinarian was >= 100 miles away or for which
      a veterinarian was not available were located in 40 US states. Overall, 61.7% of
      operations (95% CI, 60.6% to 62.9%) had used a veterinarian during the 12 months
      prior to the survey. Producers with college degrees were significantly more
      likely to use a veterinarian (675%) versus those who did not complete high school
      (52.9%). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated most
      small-scale operations had adequate access to veterinarians during 2011, but
      there seemed to be localized shortages of veterinarians in many states.

PMID- 24134587
TI  - How to attract them and keep them: the pharmacy attributes that matter to
      Australian residents with chronic conditions.
AB  - OBJECTIVE: To explore the attributes of pharmacy choice for people with chronic
      conditions. METHODS: Semi-structured interviews were conducted between May and
      October 2012, across four regions in three Australian states. Purposive sampling
      was used to recruit participants with chronic conditions and unpaid carers.
      Interviews were analysed via the constant comparison method. KEY FINDINGS: Ninety
      seven interviews were conducted. The majority of participants were regular
      patrons of one pharmacy and five attributes influenced this choice: patient
      centred care, convenience, price, personal trait or preference and
      service/medication need. Patient-centred care, such as providing individualised
      medication counselling, continuity of care, development of relationships and
      respectful advice, emerged as an important attribute. There was minimal
      discussion as to choosing a pharmacy based on the provision of professional
      services, underscoring the limited consumer knowledge of such services and
      related standards of care. CONCLUSION: Patient-centred care is an important
      attribute of quality care as perceived by people who are regular community
      pharmacy users. These findings highlight the need for pharmacy staff to implement
      a patient-centred approach to care, thus meeting the perceived needs of their
      customers. A greater effort is also necessary to raise the profile of pharmacy as
      a healthcare destination.

PMID- 24134588
TI  - Wavelength tunable single nanowire lasers based on surface plasmon polariton
      enhanced Burstein-Moss effect.
AB  - Wavelength tunable semiconductor nanowire (NW) lasers are promising for
      multifunctional applications ranging from optical communication to spectroscopy
      analysis. Here, we present a demonstration of utilizing the surface plasmon
      polariton (SPP) enhanced Burstein-Moss (BM) effect to tune the lasing wavelength
      of a single semiconductor NW. The photonic lasing mode of the CdS NW (with length
      ~10 MUm and diameter ~220 nm) significantly blue shifts from 504 to 483 nm at
      room temperature when the NW is in close proximity to the Au film. Systematic
      steady state power dependent photoluminescence (PL) and time-resolved PL studies
      validate that the BM effect in the hybrid CdS NW devices is greatly enhanced as a
      consequence of the strong coupling between the SPP and CdS excitons. With
      decreasing dielectric layer thickness h from 100 to 5 nm, the enhancement of the
      BM effect becomes stronger, leading to a larger blue shift of the lasing
      wavelength. Measurements of enhanced exciton emission intensities and
      recombination rates in the presence of Au film further support the strong
      interaction between SPP and excitons, which is consistent with the simulation
      results.

PMID- 24134590
TI  - Combined heterotopic liver-pancreas transplantation as a curative treatment for
      liver cirrhosis and diabetes mellitus in cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited disease with a defect in epithelial chloride
      transport that results in a multisystem disease. Although pulmonary disease
      remains the primary cause of morbidity and mortality, focal biliary cirrhosis and
      portal hypertension may develop in up to 8% of these patients. Liver
      transplantation (TX) is an accepted therapy and shows good results. We report on
      a patient with cystic fibrosis homozygous for the most common CFTR mutation delta
      F 508 who received a combined heterotopic liver and pancreas transplantation at
      the age of 18 yr. He suffered from CFRD, which untypically required high doses of
      insulin. In addition, the patient had pulmonary complications, was chronically
      colonized with multiresistant Pseudomonas aeruginosa (MBL) and had an allergic
      bronchopulmonary aspergillosis (ABPA). The patient remained in stable health for
      54 months post-TX and was able to live a nearly normal life. With a follow-up of
      five yr, the function of the liver and pancreas allografts was excellent.
      However, and sadly, his pulmonary function continued to deteriorate from
      progression of his CF, and he died of respiratory failure due to a severe
      pneumonia and septicemia at the age of 23 yr and five months.

PMID- 24134589
TI  - Dimethylarginine dimethylaminohydrolase II overexpression attenuates LPS-mediated
      lung leak in acute lung injury.
AB  - Acute lung injury (ALI) is a severe hypoxemic respiratory insufficiency
      associated with lung leak, diffuse alveolar damage, inflammation, and loss of
      lung function. Decreased dimethylaminohydrolase (DDAH) activity and increases in
      asymmetric dimethylarginine (ADMA), together with exaggerated oxidative/nitrative
      stress, contributes to the development of ALI in mice exposed to LPS. Whether
      restoring DDAH function and suppressing ADMA levels can effectively ameliorate
      vascular hyperpermeability and lung injury in ALI is unknown, and was the focus
      of this study. In human lung microvascular endothelial cells, DDAH II
      overexpression prevented the LPS-dependent increase in ADMA, superoxide,
      peroxynitrite, and protein nitration. DDAH II also attenuated the endothelial
      barrier disruption associated with LPS exposure. Similarly, in vivo, we
      demonstrated that the targeted overexpression of DDAH II in the pulmonary
      vasculature significantly inhibited the accumulation of ADMA and the subsequent
      increase in oxidative/nitrative stress in the lungs of mice exposed to LPS. In
      addition, augmenting pulmonary DDAH II activity before LPS exposure reduced lung
      vascular leak and lung injury and restored lung function when DDAH activity was
      increased after injury. Together, these data suggest that enhancing DDAH II
      activity may prove a useful adjuvant therapy to treat patients with ALI. 

PMID- 24134591
TI  - Author's reply to: Al-Abdi SY. Virus-inactivated plasma and intraventricular
      hemorrhage in preterm neonates.

PMID- 24134592
TI  - Repeated randomization and matching in multi-arm trials.
AB  - Cluster randomized trials with relatively few clusters have been widely used in
      recent years for evaluation of health-care strategies. The balance match weighted
      (BMW) design, introduced in Xu and Kalbfleisch (2010, Biometrics 66, 813-823),
      applies the optimal full matching with constraints technique to a prospective
      randomized design with the aim of minimizing the mean squared error (MSE) of the
      treatment effect estimator. This is accomplished through consideration of M
      independent randomizations of the experimental units and then selecting the one
      which provides the most balance evaluated by matching on the estimated propensity
      scores. Often in practice, clinical trials may involve more than two treatment
      arms and multiple treatment options need to be evaluated. Therefore, we consider
      extensions of the BMW propensity score matching method to allow for studies with
      three or more arms. In this article, we propose three approaches to extend the
      BMW design to clinical trials with more than two arms and evaluate the property
      of the extended design in simulation studies. 

PMID- 24134594
TI  - Measuring motivation: change talk and counter-change talk in cognitive behavioral
      therapy for generalized anxiety.
AB  - How clients talk about change early in treatment has been found to be a potent
      predictor of their subsequent treatment success. Studies examining such client
      motivational language (arguments for and against change) have typically been
      conducted in the context of motivational interviewing for addictions. This study
      examined the capacity of client motivational language to predict treatment
      outcomes in the context of cognitive behavioral therapy (CBT) for generalized
      anxiety. Client early in-session statements against change (counter-change talk)
      were found to be robust predictors of post-treatment worry scores and
      differentiated treatment responders from nonresponders. Moreover, client
      motivational language predicted outcomes beyond initial symptom severity and self
      report measures of motivation. These results strongly support the relevance of
      client motivational language outcomes in CBT and provide a foundation for
      advancing research on motivation for change in a CBT context.

PMID- 24134597
TI  - New supramolecular Au(I)-Cu(I) complex as potential luminescent label for
      proteins.
AB  - A novel supramolecular [Au6Cu2(C2C6H4-4-COONC4H4O2)6(Ph2PC6H4PPh2)3](PF6)2
      complex functionalized with a succinimide ester alkynyl substituent has been
      synthesized and characterized using X-ray crystallography, mass spectrometry, and
      NMR spectroscopy. Like the other complexes of this class, it demonstrates bright
      emission in acetone and dichloromethane solutions with the excited state lifetime
      in a microsecond domain. This complex readily reacts with a surface amine group
      of proteins/enzymes (human serum albumin (HSA), rabbit anti-HSA antibodies,
      soybean trypsin inhibitor, and alpha-chymotrypsin) to give covalent conjugates,
      which contain up to five molecules of the luminescent label bound to the
      biomolecule. The conjugates keep a high level of the phosphorescent label
      emission, but in contrast to the parent complex molecule, display excellent
      solubility and high stability in physiological media. Investigation of the
      biological activity of the conjugates also showed that the specific structure of
      the biomolecules remained nearly unchanged upon bonding with the label, which is
      indicative of a very prospective of the conjugates application in biomolecular
      detection. 

PMID- 24134593
TI  - Characteristics of the pediatric patients treated by the Pediatric Emergency Care
      Applied Research Network's affiliated EMS agencies.
AB  - OBJECTIVE: To describe pediatric patients transported by the Pediatric Emergency
      Care Applied Research Network's (PECARN's) affiliated emergency medical service
      (EMS) agencies and the process of submitting and aggregating data from diverse
      agencies. METHODS: We conducted a retrospective analysis of electronic patient
      care data from PECARN's partner EMS agencies. Data were collected on all EMS runs
      for patients less than 19 years old treated between 2004 and 2006. We conducted
      analyses only for variables with usable data submitted by a majority of
      participating agencies. The investigators aggregated data between study sites by
      recoding it into categories and then summarized it using descriptive statistics.
      RESULTS: Sixteen EMS agencies agreed to participate. Fourteen agencies (88%)
      across 11 states were able to submit patient data. Two of these agencies were
      helicopter agencies (HEMS). Mean time to data submission was 378 days (SD 175).
      For the 12 ground EMS agencies that submitted data, there were 514,880
      transports, with a mean patient age of 9.6 years (SD 6.4); 53% were male, and 48%
      were treated by advanced life support (ALS) providers. Twenty-two variables were
      aggregated and analyzed, but not all agencies were able to submit all analyzed
      variables and for most variables there were missing data. Based on the available
      data, median response time was 6 minutes (IQR: 4-9), scene time 15 minutes (IQR:
      11-21), and transport time 9 minutes (IQR: 6-13). The most common chief
      complaints were traumatic injury (28%), general illness (10%), and respiratory
      distress (9%). Vascular access was obtained for 14% of patients, 3% received
      asthma medication, <1% pain medication, <1% assisted ventilation, <1% seizure
      medication, <1% an advanced airway, and <1% CPR. Respiratory rate, pulse,
      systolic blood pressure, and GCS were categorized by age and the majority of
      children were in the normal range except for systolic blood pressure in those
      under one year old. CONCLUSIONS: Despite advances in data definitions and
      increased use of electronic databases nationally, data aggregation across EMS
      agencies was challenging, in part due to variable data collection methods and
      missing data. In our sample, only a small proportion of pediatric EMS patients
      required prehospital medications or interventions.

PMID- 24134598
TI  - Kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon:
      ultrastructural observation and immunohistochemistry staining reveal the trapping
      of blood components.
AB  - Kaposiform hemangioendothelioma (KHE), a borderline tumor of endothelial origin,
      is associated with Kasabach-Merritt phenomenon, characterized by profound
      thrombocytopenia and consumptive coagulopathy resulting from the localized
      intravascular coagulation (LIC) in the tumor. Previous studies have suggested
      that the trapping of blood components, including platelets, may underlie the LIC
      in KHE. However, more evidence is needed to support this hypothesis. In this
      study, one case of a Chinese infant with a KHE in the left arm was complicated by
      Kasabach-Merritt phenomenon. The tumor was partially resected and the sample was
      used for ultrastructural observation and immunohistochemistry staining of Glut-1.
      Ultrastructural observation found the trapping of erythrocytes, platelets,
      macrophages, and lymphocytes in the slit-like channels of the tumor nodules, and
      phagocytic vesicles in the cytoplasm of neoplastic cells. Immunohistochemistry
      staining further showed numerous Glut-1(+) erythrocytes in the channels. In
      conclusion, our results provided compelling morphological evidence of the
      trapping of blood components in KHE, which may interpret the LIC in the tumor and
      subsequent consumptive coagulopathy.

PMID- 24134599
TI  - Arg972 Insulin receptor substrate-1 is associated with decreased serum
      angiotensin-converting enzyme 2 levels in acute myocardial infarction patients:
      in vivo and in vitro evidence.
AB  - BACKGROUND: Activation of the renin-angiotensin system (RAS) plays a critical
      role in the pathophysiology of myocardial infarction (MI) and the development of
      heart failure. Both angiotensin-converting enzyme 2 (ACE2) and insulin/insulin
      receptor substrate-1 (IRS-1) show cardioprotective effects after acute MI. The
      Arg972 IRS-1 polymorphism is associated with diminished activity of insulin. In
      the present study, we explored the association among Arg972 IRS-1, acute MI, and
      serum levels of ACE2. METHODS: A total of 711 subjects, including 351 subjects
      with first-time acute MI and 360 subjects without a history of MI were genotyped
      for Arg972 IRS-1 polymorphism. Serum levels of ACE2 and MI severity scores were
      determined. Primary human cardiomyocytes with overexpression of wild type IRS-1
      or Arg972 IRS-1 or knockdown of endogenous IRS-1 were exposed to normoxia and
      hypoxia, and the expression levels of ACE2 were determined. RESULTS: The serum
      ACE2 level was significantly increased in acute MI patients compared with that of
      non-MI controls. Compared with wild type IRS-1 carriers, Arg972 IRS-1 carriers
      exhibited decreased serum ACE2 levels and increased MI severity scores after MI.
      Our in vitro data demonstrate that impairment of insulin/IRS-1/PI3K signaling by
      overexpression of Arg972-IRS-1, knockdown of endogenous IRS-1, or PI3K inhibitor
      can abolish hypoxia-induced IRS-1-associated PI3K activity and ACE2 expression in
      human cardiomyocytes, which suggests a causal relationship between Arg972-IRS-1
      and decreased serum ACE2 levels in acute MI patients. Our in vitro data also
      indicate that insulin/IRS-1/PI3K signaling is required for ACE2 expression in
      cardiomyocytes, and that hypoxia can enhance the induction effect of insulin/IRS
      1/PI3K signaling on ACE2 expression in cardiomyocytes. CONCLUSIONS: This study
      provides the first evidence of crosstalk between insulin/IRS-1/PI3K signaling and
      RAS after acute MI, thereby adding fresh insights into the pathophysiology and
      treatment of acute MI.

PMID- 24134600
TI  - Delivery of host cell-directed therapeutics for intracellular pathogen clearance.
AB  - Intracellular pathogens present a major health risk because of their innate
      ability to evade clearance. Their location within host cells and ability to react
      to the host environment by mutation or transcriptional changes often enables
      survival mechanisms to resist standard therapies. Host-directed drugs do not
      target the pathogen, minimizing the potential development of drug resistance;
      however, they can be difficult to deliver efficiently to intracellular sites.
      Vehicle delivery of host-mediated response drugs not only improves drug
      distribution and toxicity profiles, but can reduce the total amount of drug
      necessary to clear infection. In this article, we will review some host-directed
      drugs and current drug delivery techniques that can be used to efficiently clear
      intracellular infections. 

PMID- 24134601
TI  - Experimental models to study drug distributions in tissue using MALDI mass
      spectrometry imaging.
AB  - Requirements for patient safety and improved efficacy are steadily increasing in
      modern healthcare and are key drivers in modern drug development. New drug
      characterization assays are central in providing evidence of the specificity and
      selectivity of drugs. Meeting this need, matrix-assisted laser desorption
      ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug
      localization within microenvironmental tissue compartments. Thin sections of
      human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs
      by either spotting or submerging. These drugs, the epidermal growth factor
      receptor antagonists, erlotinib (Tarceva) and gefitinib (Iressa), and the
      acetylcholine receptor antagonist, tiotropium, were characterized by
      microenvironment localization. Intact tissue blocks were also immersed in drug
      solution, followed by sectioning. MALDI-MSI was then performed using a Thermo
      MALDI LTQ Orbitrap XL instrument to localize drug-distribution patterns. We
      propose three MALDI-MSI models measuring drug disposition that have been used to
      map the selected compounds within tissue compartments of tumors isolated from
      lung cancer patients. 

PMID- 24134602
TI  - Insulin degludec: a new insulin for today?

PMID- 24134603
TI  - Effects of three antagonists on selected pharmacodynamic effects of sublingually
      administered detomidine in the horse.
AB  - OBJECTIVE: To describe the effects of alpha2 -adrenergic receptor antagonists on
      the pharmacodynamics of sublingual (SL) detomidine in the horse. STUDY DESIGN:
      Randomized crossover design. ANIMALS: Nine healthy adult horses with an average
      age of 7.6 +/- 6.5 years. METHODS: Four treatment groups were studied: 1) 0.04 mg
      kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by
      0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL
      followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1)
      detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse
      received all treatments with a minimum of 1 week between treatments. Blood
      samples were obtained and plasma analyzed for yohimbine, atipamezole and
      tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral
      effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma
      proteins were monitored. RESULTS: Chin-to-ground distance increased following
      administration of the antagonists, however, this effect was transient, with a
      return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia
      and increased incidence of atrioventricular blocks were either transiently or
      incompletely antagonized by all antagonists. PCV and glucose concentrations
      increased with tolazoline administration, and atipamezole subjectively increased
      urination frequency but not volume. CONCLUSIONS AND CLINICAL RELEVANCE: At the
      doses administered in this study, the alpha2 -adrenergic antagonistic effects of
      tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited
      by SL administration of detomidine are transient and incomplete.

PMID- 24134604
TI  - Immunotherapy for Hymenoptera venom allergy: too expensive for European health
      care?

PMID- 24134605
TI  - A prospective cohort study of prognosis for newly diagnosed epilepsy in east
      China.
AB  - BACKGROUND: Limited data are available on the outcome of antiepileptic drug
      treatment response in patients of Chinese Han ethnicity with newly diagnosed
      epilepsy. We sought to explore the prognosis with antiepileptic drug treatment
      and to identify the predictors of poor drug control of seizures in these
      patients. METHODS: For at least 2 years, we prospectively followed up a cohort of
      patients with newly diagnosed epilepsy and analyzed the response to each
      antiepileptic drug. Cumulative risk for seizure relapse after initial remission
      achieved was estimated. The patients were divided into two groups (poor and good
      control) and compared for clinical characteristics. RESULTS: A total of 180
      patients were included. Early remission was reached in 125 (69.44%) patients, 19
      (10.56%) patients entered late remission, while 36 (20%) patients failed to
      achieve remission. The relapse rates were 19.5% at 2 years and 31.9% at 3 years
      of the follow-up. The response rates of the first throughout the fourth treatment
      regimens were 60.0%, 16.1%, 2.8%, and 0.6%, respectively. Multiple seizure types
      and changes in seizure type during treatment were significantly (p = 0.013 and
      0.047, respectively) associated with a poor control. CONCLUSIONS: The prognosis
      of the majority of patients with newly diagnosed epilepsy is good and the
      clinical pattern of epilepsy during treatment is complex. The chances of seizure
      control declines with each subsequent treatment regimen. The prognosis for
      patients with multiple seizure types and seizure type changes during treatment is
      unfavorable.

PMID- 24134606
TI  - Electrodeposition of polydopamine thin films for DNA patterning and microarrays.
AB  - The controlled electrodeposition of functional polydopamine (PDA) thin films from
      aqueous dopamine solutions is demonstrated with a combination of
      electrochemistry, atomic force microscopy (AFM), and surface plasmon resonance
      (SPR) measurements. PDA micropatterns are then fabricated by electrodeposition on
      micrometer length scale gold electrodes and used for attaching amino-modified
      single-stranded DNA (ssDNA). After hybridization with fluorescently labeled
      ssDNA, the fluorescence microscopy characterization reveals that: (i) PDA can be
      toposelectively deposited at the microscale and (ii) electrochemically deposited
      PDA can be functionalized with amino-terminated ssDNA using the same chemistry as
      that for spontaneously deposited PDA. Finally, the application of
      electrodeposited PDA thin films to fabricate ssDNA microarrays is reported using
      SPR imaging (SPRI) measurements for the detection of DNA and DNA-modified gold
      nanoparticles. 

PMID- 24134607
TI  - Allogeneic stem cell transplantation in patients with aggressive primary
      cutaneous T-cell lymphoma - a case series of the ADF working group "cutaneous
      lymphomas".
AB  - BACKGROUND: Allogeneic stem cell transplantation (alloSCT) is a treatment option
      for primary cutaneous T-cell lymphomas that may induce long-lasting complete
      remissions. Little information is available on safety and efficacy. PATIENTS AND
      METHODS: We retrospectively reviewed the data from patients with primary
      cutaneous T-cell lymphoma treated in the Departments of Dermatology of the
      Universities of Bochum, Mannheim and Cologne who received subsequent alloSCT
      between 2005 and 2012. RESULTS: Nine patients with aggressive primary cutaneous T
      cell-lymphoma received alloSCT. With a follow-up of 14 to 36 months after
      transplantation, 4 patients are alive and in complete remission. Two patients had
      recurrent disease post-transplantation, which was successfully treated with donor
      lymphocyte infusions. Non-relapse mortality was observed in three patients in
      advanced disease stages within six months after alloSCT. One patient showed only
      partial remission and died of disease after 32 months and one patient died 26
      months after alloSCT with cause of death unknown. CONCLUSIONS: This report
      documents the possible benefit of a graft-versus-lymphoma effect in primary
      cutaneous T-cell lymphoma, as has been observed for other T-cell malignancies and
      emphasizes that alloSCT warrants further studies in this setting.

PMID- 24134608
TI  - The effect of statin therapy withdrawal on monocyte subsets.
AB  - BACKGROUND: Three functionally distinct monocyte subsets have been identified.
      Statins are of undoubted effect in atherosclerosis and have numerous pleiotropic
      effects that contribute to their clinical success, but the effect of these drugs
      on monocyte subsets is unclear. We hypothesised a beneficial effect of statins on
      key receptor expression by monocyte subsets. MATERIAL AND METHODS: Effects of
      temporal (2 weeks) cessation of statin therapy by 66 patients with stable
      coronary artery disease on monocyte subsets [CD14++CD16-CCR2+ (Mon1),
      CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)], their aggregates with
      platelets and their expression of a number of receptors involved in inflammation
      (IL-6 receptor), adhesion [vascular cell adhesion molecule (VCAM)], angiogenesis
      [vascular endothelial growth factor (VEGF)] and repair were assessed by flow
      cytometry. RESULTS: Statin cessation did not lead to any significant changes in
      absolute numbers of monocyte subsets or the degree of their aggregation with
      platelets. All monocyte subsets showed significant downregulation of expression
      of vascular endothelial factor receptor 2, Tie2 and Toll-like receptor-4 (TLR4;
      all changes P < 0.01). Expression of CXCR4 was only reduced in Mon1 cells (P =
      0.013). There was no significant change in the expression of CD14, CD16, CCR4,
      IL6 receptor and VCAM (all P = NS). CONCLUSIONS: Statin withdrawal does not
      affect counts of any of monocyte subsets, but leads to downregulation of
      expression of TLR4 and receptors related to angiogenesis on all subsets, as well
      as a decrease in density of CXCR4 expression on 'classical' Mon1. These data
      provide further support of pleiotropic effects of statins and their effects on
      monocyte pro-angiogenic and proreparative characteristics.

PMID- 24134609
TI  - JNK1 and JNK2 regulate alpha-SMA in hepatic stellate cells during CCl4 -induced
      fibrosis in the rat liver.
AB  - Following liver injuries, hepatic stellate cells (HSCs) express alpha-SMA.
      Mitogen activated protein kinase (MAPK) signaling pathways mediate alpha-SMA
      expression in distinct cell types. However, the regulation of alpha-SMA
      expression by MAPKs in HSCs has been rarely studied. We aimed to study the role
      of MAPKs in the activation of HSCs during liver fibrosis. Liver fibrosis of rats
      was induced by carbon tetrachloride. HSC-T6 cells, murine embryonic fibroblasts,
      JNK1(-/-) and JNK2(-/-) cells were used for in vitro studies.
      Immunohistochemistry and immunoblot analysis were used. We have found that the
      expression of JNK and alpha-SMA co-localized in HSCs during liver fibrosis, but
      ERK and p38 expressed in macrophages. The expression of alpha-SMA was up
      regulated by JNK1 and JNK2 in non-stress condition. Under TGF-beta stimulation,
      however, the level alpha-SMA expression was increased by only JNK1, but not
      significantly changed by JNK2. We suggest that JNKs are responsible for alpha-SMA
      regulation, and especially JNK1 has a major role in up-regulation of alpha-SMA
      expression in HSCs under stress condition induced by TGF-beta during liver
      fibrosis. 

PMID- 24134610
TI  - Influence of substituting dietary soybean for air-classified sunflower
      (Helianthus annuus L.) meal on egg production and steroid hormones in early-phase
      laying hens.
AB  - Soybean meal (SBM) is the most widely and expensive protein source used in the
      formulation of poultry diets; however, when the price of SBM increases, poultry
      nutritionists seek alternative sources that are more economical in formulating
      least-cost rations. This research aimed to evaluate the effects of dietary air
      classified sunflower meal (SFM) on some productive parameters and plasma steroid
      hormones in laying hens. In this trial, 20-week-old laying hens (ISA Brown
      strain) in the early phase of production were randomly assigned to two groups and
      fed wheat middlings-based diets containing soybean (135 g/kg; 48% CP) or air
      classified SFM (160 g/kg; 41% CP) as the main protein source. Laying performance,
      egg size and feed conversion ratio were evaluated for 10 week. Plasma steroid
      hormones (progesterone and oestradiol) in the hens were quantified weekly.
      Substituting SBM with air-classified SFM did not change (p > 0.05) the hens'
      growth performance, whereas feed consumption and efficiency were positively
      influenced (p < 0.05) by SFM treatment. Egg production rate was improved in hens
      fed the SFM diet (p < 0.05), as well as the percentage of medium-size eggs that
      was higher for SFM treatment (p < 0.05). Steroid hormones levels were affected by
      dietary treatment (p < 0.01). From our findings, it could be effective to include
      air-classified SFM in early-phase laying hen diets as an alternative protein
      source substituting SBM, without negative influence on productive performance and
      egg traits, reducing also the production costs. 

PMID- 24134611
TI  - New understanding of hardening mechanism of TiN/SiNx-based nanocomposite films.
AB  - In order to clarify the controversies of hardening mechanism for TiN/SiNx-based
      nanocomposite films, the microstructure and hardness for TiN/SiNx and TiAlN/SiNx
      nanocomposite films with different Si content were studied. With the increase of
      Si content, the crystallization degree for two series of films firstly increases
      and then decreases. The microstructural observations suggest that when SiNx
      interfacial phase reaches to a proper thickness, it can be crystallized between
      adjacent TiN or TiAlN nanocrystallites, which can coordinate misorientations
      between nanocrystallites and grow coherently with them, resulting in blocking of
      the dislocation motions and hardening of the film. The microstructure of TiN/SiNx
      based nanocomposite film can be characterized as the nanocomposite structure with
      TiN-based nanocrystallites surrounded by crystallized SiNx interfacial phase,
      which can be denoted by nc-TiN/c-SiNx model ('c' before SiNx means crystallized)
      and well explain the coexistence between nanocomposite structure and columnar
      growth structure within the TiN/SiNx-based film. 

PMID- 24134612
TI  - Polarity-driven nonuniform composition in InGaAs nanowires.
AB  - Manipulating the composition and morphology of semiconductor nanowires in a
      precisely controlled fashion is critical in developing nanowire devices. This is
      particularly true for ternary III-V nanowires. Many studies have shown the
      complexities within those nanowires. Here we report our findings of compositional
      irregularity in the shells of core-shell InGaAs nanowires with zinc-blende
      structure. Such an effect is caused by the crystal polarity within III-V zinc
      blende lattice and the one-dimensional nature of nanowires that allows the
      formation of opposite polar surfaces simultaneously on the nanowire sidewalls.
      This polarity-driven effect in III-V nanowires may be utilized in manipulating
      the composition and morphology of III-V nanowires for device applications. 

PMID- 24134613
TI  - Flame figures in histology associated with allergic contact dermatitis from a
      henna tattoo.

PMID- 24134614
TI  - Multilocus analyses reveal little evidence for lineage-wide adaptive evolution
      within major clades of soft pines (Pinus subgenus Strobus).
AB  - Estimates from molecular data for the fraction of new nonsynonymous mutations
      that are adaptive vary strongly across plant species. Much of this variation is
      due to differences in life history strategies as they influence the effective
      population size (Ne ). Ample variation for these estimates, however, remains even
      when comparisons are made across species with similar values of Ne . An open
      question thus remains as to why the large disparity for estimates of adaptive
      evolution exists among plant species. Here, we have estimated the distribution of
      deleterious fitness effects (DFE) and the fraction of adaptive nonsynonymous
      substitutions (alpha) for 11 species of soft pines (subgenus Strobus) using DNA
      sequence data from 167 orthologous nuclear gene fragments. Most newly arising
      nonsynonymous mutations were inferred to be so strongly deleterious that they
      would rarely become fixed. Little evidence for long-term adaptive evolution was
      detected, as all 11 estimates for alpha were not significantly different from
      zero. Nucleotide diversity at synonymous sites, moreover, was strongly correlated
      with attributes of the DFE across species, thus illustrating a strong consistency
      with the expectations from the Nearly Neutral Theory of molecular evolution.
      Application of these patterns to genome-wide expectations for these species,
      however, was difficult as the loci chosen for the analysis were a biased set of
      conserved loci, which greatly influenced the estimates of the DFE and alpha. This
      implies that genome-wide parameter estimates will need truly genome-wide data, so
      that many of the existing patterns documented previously for forest trees (e.g.
      little evidence for signature of selection) may need revision. 

PMID- 24134615
TI  - Isotopically enriched 13C diffusion-ordered NMR spectroscopy: analysis of
      methyllithium.
AB  - We report the development of isotopic-labeled (13)C diffusion-ordered NMR
      spectroscopy (DOSY) NMR with diffusion coefficient-formula weight (D-FW) analysis
      and its application in characterizing the aggregation state of methyllithium
      aggregates and complexes with several widely used diamines. Commercially
      available (13)C-labeled benzene and several easily synthesized (13)C-labeled
      compounds using (13)C-labeled iodomethane as the isotopic source are developed as
      internal references for diffusion-formula weight analysis (D-FW). The technique
      greatly expands the applicability of DOSY D-FW analysis to a much wider variety
      of compounds because of isotopic labeling. These results reveal that
      methyllithium exists as a tetrasolvated tetramer in diethyl ether and exclusively
      as bis-solvated dimers with chelating diamines. 

PMID- 24134616
TI  - Infectivity and transmissibility of H9N2 avian influenza virus in chickens and
      wild terrestrial birds.
AB  - Genetic changes in avian influenza viruses influence their infectivity, virulence
      and transmission. Recently we identified a novel genotype of H9N2 viruses in
      widespread circulation in poultry in Pakistan that contained polymerases (PB2,
      PB1 and PA) and non-structural (NS) gene segments identical to highly pathogenic
      H7N3 viruses. Here, we investigated the potential of these viruses to cause
      disease and assessed the transmission capability of the virus within and between
      poultry and wild terrestrial avian species. Groups of broilers, layers, jungle
      fowl, quail, sparrows or crows were infected with a representative strain
      (A/chicken/UDL-01/08) of this H9N2 virus and then mixed with naive birds of the
      same breed or species, or different species to examine transmission. With the
      exception of crows, all directly inoculated and contact birds showed clinical
      signs, varying in severity with quail showing the most pronounced clinical signs.
      Virus shedding was detected in all infected birds, with quail showing the
      greatest levels of virus secretion, but only very low levels of virus were found
      in directly infected crow samples. Efficient virus intra-species transmission was
      observed within each group with the exception of crows in which no evidence of
      transmission was seen. Interspecies transmission was examined between chickens
      and sparrows and vice versa and efficient transmission was seen in either
      direction. These results highlight the ease of spread of this group of H9N2
      viruses between domesticated poultry and sparrows and show that sparrows need to
      be considered as a high risk species for transmitting H9N2 viruses between
      premises.

PMID- 24134617
TI  - Superhydrophobic surface-enhanced Raman scattering platform fabricated by
      assembly of Ag nanocubes for trace molecular sensing.
AB  - An analytical platform suitable for trace detection using a small volume of
      analyte is pertinent to the field of toxin detection and criminology. Plasmonic
      nanostructures provide surface-enhanced Raman scattering (SERS) that can
      potentially achieve trace toxins and/or molecules detection. However, the
      detection of highly diluted, small volume samples remains a challenge. Here, we
      fabricate a superhydrophobic SERS platform by assembling Ag nanocubes that
      support strong surface plasmon and chemical functionalization for trace detection
      with sample volume of just 1 MUL. Our strategy integrates the intense
      electromagnetic field confinement generated by Ag nanocubes with a
      superhydrophobic surface capable of analyte concentration to lower the molecular
      detection limit. Single crystalline Ag nanocubes are assembled using the Langmuir
      Blodgett technique to create surface roughness. To create a stable
      superhydrophobic SERS platform, an additional 25 nm Ag coating is evaporated over
      the Ag nanocubes to "weld" the Ag nanocubes onto the substrate followed by
      chemical functionalization with perfluorodecanethiol. The resulting substrate has
      an advancing contact angle of 169 degrees  +/- 5 degrees . Our superhydrophobic
      platform confines analyte molecules within a small area and prevents the random
      spreading of molecules. An analyte concentrating factor of 14-fold is attained,
      as compared to a hydrophilic surface. Consequently, the detection limit of our
      superhydrophobic SERS substrate reaches 10(-16) M (100 aM) for rhodamine 6G using
      1 MUL analyte solutions. An analytical SERS enhancement factor of 10(11) is
      achieved. Our protocol is a general method that provides a simple, cost-effective
      approach to develop a stable and uniform superhydrophobic SERS platform for trace
      molecular sensing. 

PMID- 24134618
TI  - Predictive value of striae gravidarum severity for intraperitoneal adhesions or
      uterine scar healing in patients with previous caesarean delivery.
AB  - OBJECTIVE: Previous abdominal operations might cause severe intraperitoneal
      adhesions (IPA), which can complicate caesarean section (CS) procedures. When
      selecting the mode and timing of delivery, obstetricians are also curious about
      uterine scar healing if the previous operation was a CS. Uterine scar thickness
      is an indicator of uterine scar healing. We aimed to evaluate the possible
      predictive value of striae gravidarum (SG) on IPA formation and uterine scar
      thickness (UST). METHODS: Fifty-five women with a previous CS history were
      evaluated for SG Davey Score. They were investigated for IPAs and lower segment
      uterine scar thickness during the current CS operation. RESULTS: Out of the
      patients with no SG (n = 11), mild SG (n = 10) and severe SG (n = 34), 1 (9.1%),
      3 (30%) and 17 (50%) had IPA, respectively (p = 0.044). The mean uterine scar
      thicknesses in the no SG, mild SG and severe SG groups were 3.82 +/- 4.04, 5.20
      +/- 4.13 and 5.18 +/- 3.52, respectively (p = 0.561). CONCLUSIONS: To the best of
      our knowledge, this was the first study to investigate the relationship between
      SG and IPA and uterine scar thickness. The SG status of a patient with a previous
      delivery and abdominal operation history might help predict IPA status before
      planning a new operation.

PMID- 24134619
TI  - Dual sustained release delivery system for multiple route therapy of an antiviral
      drug.
AB  - CONTEXT: The first successful molecule against herpes infections was Acyclovir,
      which competes with new generations in the market, with its potential activity.
      The major physicochemical constraints and pharmacokinetics of Acyclovir such as
      low solubility, poor permeability, less half-life, high dose has initiated many
      researchers to develop diverse modified release dosage forms. OBJECTIVE: The
      objective of this work was to design polymeric nanoparticles of Acyclovir and
      then incorporate the drug-loaded nanoparticles within an in situ gelling system
      to provide dual sustained release effect, whereby the duration of action and
      bioavailability through different routes of administration could be improved.
      MATERIALS AND METHODS: The formulation was designed through 3(2) factorial
      design, first developing the nanoparticles using Polycaprolactone and Pluronic
      F127 by Solvent evaporation process, followed by dispersion of the suspended
      nanoparticles into thermosensitive in situ gelling system of Pluronic F127 with
      Carbopol. RESULTS AND DISCUSSION: The characterization of the nanoparticles and
      its sol-gel system performed through zeta sizer, SEM, XRD, TG-DSC, FTIR and
      rheology helped to optimize the formulation. The drug release could be sustained
      to 60% and 30% at eight hours, for the nanoparticles and their in situ gel
      systems, respectively, with non-Fickian diffusion mechanism of drug release. The
      test for % cell viability with NIH3T3 cell line revealed low level of toxicity
      for the nanoparticles. CONCLUSION: The statistical significance obtained for the
      trail formulations experimentally proved its suitability for this dosage form
      design to achieve desired level of drug release.

PMID- 24134620
TI  - Identification of differentially expressed water-insoluble proteins in the
      encystment process of Colpoda cucullus by two-dimensional electrophoresis and LC
      MS/MS analysis.
AB  - In the encystment process of the ciliate protist Colpoda cucullus, we observed
      that the cell total protein abundance was reduced at 12 h-1 d after the onset of
      encystment induction subsequent to the reduction in mRNA abundance. We analyzed
      the alteration of the expression levels of water-insoluble proteins by two
      dimensional polyacrylamide gel electrophoresis using polyoxyethylene (20)
      sorbitan monooleate (Tween-80), and we identified proteins whose expression
      levels were altered in the encystment process by a liquid chromatography tandem
      mass spectrometry analysis. The expression level of a 60-kDa protein (p60; heat
      shock protein 60) was temporarily enhanced and that of a 55-kDa protein (p55;
      actin) and a 49-kDa protein (p49; actin) was enhanced in the Colpoda encystment
      process. In mature cysts, the expression level of p55 and p49 tended to be
      reduced, whereas the expression level of a 50-kDa protein (p50d; alpha-tubulin),
      a 25-kDa protein (p25; alpha-tubulin) and a 52-kDa protein (p52c; beta-tubulin)
      was enhanced.

PMID- 24134622
TI  - Hypoxia, leptin, and vascular endothelial growth factor stimulate vascular
      endothelial cell differentiation of human adipose tissue-derived stem cells.
AB  - The plasticity of human adipose tissue-derived stem cells (hASCs) is promising,
      but differentiation in vitro toward endothelial cells is poorly understood. Flow
      cytometry demonstrated that hASCs isolated from excised fat tissue were positive
      for CD29, CD44, CD70, CD90, CD105, and CD166 and negative for the endothelial
      marker CD31, and the hematopoietic cell markers CD34 and CD133. hASCs
      differentiated into adipocytes after cultivation in adipogenic medium. Exposure
      of hASCs for 10 days under hypoxia (3% oxygen) in combination with leptin
      increased the percentage of CD31(+) endothelial cells as well as CD31, VE
      Cadherin, Flk-1, Tie2, von Willebrand factor, and endothelial cell nitric oxide
      synthase mRNA expression. This was enhanced on co-incubation of vascular
      endothelial growth factor (VEGF) and leptin, whereas VEGF alone was not
      sufficient. Moreover, hASCs cultured on a matrigel surface under
      hypoxia/VEGF/leptin, showed a stable branching network. Hypoxic conditions
      significantly decreased apoptosis as evaluated by cleaved caspase-3, and
      increased prolyl hydroxylase domain 3 mRNA expression. Hypoxia increased
      expression of VEGF as well as leptin transcripts, which were significantly
      inhibited on co-incubation with either VEGF or leptin or a combination of both.
      Furthermore, leptin treatment of hypoxic cells increased the expression of the
      long/signaling form of the leptin receptor (ObRL), which was augmented on co
      incubation with VEGF. The observed endothelial differentiation was dependent on
      the Akt pathway, as co-administration with Akt inhibitor abolished the observed
      effects. In conclusion, our data demonstrate that hASCs can be efficiently
      differentiated to endothelial cells by mimicking the hypoxic and pro-angiogenic
      microenvironment of adipose tissue.

PMID- 24134621
TI  - Dysregulation of galectin-3. Implications for Hermansky-Pudlak syndrome pulmonary
      fibrosis.
AB  - The etiology of Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis (HPSPF), a
      progressive interstitial lung disease with high mortality, is unknown. Galectin-3
      is a beta-galactoside-binding lectin with profibrotic effects. The objective of
      this study was to investigate the involvement of galectin-3 in HPSPF. Galectin-3
      was measured by ELISA, immunohistochemistry, and immunoblotting in human
      specimens from subjects with HPS and control subjects. Mechanisms of galectin-3
      accumulation were studied by quantitative RT-PCR, Northern blot analysis,
      membrane biotinylation assays, and rescue of HPS1-deficient cells by
      transfection. Bronchoalveolar lavage galectin-3 concentrations were significantly
      higher in HPSPF compared with idiopathic pulmonary fibrosis or that from normal
      volunteers, and correlated with disease severity. Galectin-3 immunostaining was
      increased in HPSPF compared with idiopathic pulmonary fibrosis or normal lung
      tissue. Fibroblasts from subjects with HPS subtypes associated with pulmonary
      fibrosis had increased galectin-3 protein expression compared with cells from
      nonfibrotic HPS subtypes. Galectin-3 protein accumulation was associated with
      reduced Galectin-3 mRNA, normal Mucin 1 levels, and up-regulated microRNA-322 in
      HPSPF cells. Membrane biotinylation assays showed reduced galectin-3 and normal
      Mucin 1 expression at the plasma membrane in HPSPF cells compared with control
      cells, which suggests that galectin-3 is mistrafficked in these cells.
      Reconstitution of HPS1 cDNA into HPS1-deficient cells normalized galectin-3
      protein and mRNA levels, as well as corrected galectin-3 trafficking to the
      membrane. Intracellular galectin-3 levels are regulated by HPS1 protein. Abnormal
      accumulation of galectin-3 may contribute to the pathogenesis of HPSPF. 

PMID- 24134623
TI  - Blood microvessel density, lymphatic microvessel density and lymphatic invasion
      in predicting melanoma metastases: systematic review and meta-analysis.
AB  - In malignant melanoma (MM) there is an urgent need to identify new markers with
      predictive value superior to the traditional clinical and histological
      parameters. Angiogenesis and lymphangiogenesis have been recognized as critical
      processes in tumour growth and metastasis development, and numerous studies have
      evaluated the significance of these parameters in predicting the prognosis in
      solid tumours, including MM. We set out to determine whether angiogenesis,
      lymphangiogenesis and lymphatic invasion (LI) are valuable prognostic markers in
      MM. We systematically reviewed the available literature and subsequently
      performed a meta-analysis on the compiled data. To be eligible for the systematic
      review, a study had to provide the microvessel density (MVD), the lymphatic
      vessel density (LVD) or information about LI, assessed by immunohistochemistry on
      the primary site in patients with MM. To be evaluable for the meta-analysis, a
      study also had to provide information on clinical outcome. We approached selected
      studies with the Reporting recommendations for tumour marker (REMARK) criteria,
      verifying whether they had followed the recommendations. In total, nine
      angiogenesis, seven lymphangiogenesis and 10 LI studies were included in our meta
      analysis, representing 419, 474 and 802 patients, respectively. Using meta
      analysis, we showed that peritumoral LVD and the presence of LI have prognostic
      value for patients with MM. In contrast, MVD and intratumoral LVD did not have
      prognostic value in these patients. LVD and LI seem to have prognostic value for
      patients with MM. 

PMID- 24134624
TI  - Mild solvothermal syntheses of thioargentates A-Ag-S (A = K, Rb, Cs) and A-Ag-Ge
      S (A = Na, Rb): crucial role of excess sulfur.
AB  - A series sulfides of A-Ag-S (1-3; A = K, Rb, Cs), Na5AgGe2S7 (4), and Rb2Ag2GeS4
      (5) have been prepared solvothermally in the presence of excess sulfur. Among
      these compounds, 4 is a new compound that has a novel layered structure; the
      others were obtained under mild conditions. The results showed that excess sulfur
      could increase the solubility of silver sulfide and lower the synthetic
      temperature effectively. The mineralizer effect of excess sulfur is discussed in
      detail. 

PMID- 24134625
TI  - Unfit for duty? Evaluation of 4 years of paramedic preemployment fitness
      screening test results.
AB  - BACKGROUND: Preemployment testing is utilized by many ambulance services.
      Surprisingly, there is limited published research on the efficacy of this testing
      in determining an employee's ability to complete the requirements of this
      physically demanding occupation. OBJECTIVES: The purpose of this study was to
      analyze the preemployment fitness test results from a 4-year cohort of paramedic
      students from an Australian university. To date, no published studies have
      reported on the fitness test scores for paramedic students or on whether overall
      test score is biased toward any particular test components. Similarly, no data
      have been presented on whether there are gender differences in scores for
      individual test components or overall test score. METHODS: Retrospective cohort
      study of de-identified data from 4 years of data from Paramedic Science students
      (n = 251) (mean age = 24.9 years). Data were recorded from the Queensland
      Ambulance Service (QAS) Health Related Fitness Test (HRFT), a preemployment
      fitness test used by an Australian state ambulance service. HRFT score is
      calculated out of a possible 100 points and is based on performance scores in
      nine component fitness tests. Raw test scores for each of these component tests
      are ranked on a 0-4 scale prior to these data being scaled and summed to generate
      the overall HRFT score. An overall score >24.99 is awarded a "Pass." Results.
      Five individuals failed to "Pass" the HRFT. Overall HRFT scores were influenced
      significantly by performance in the strength tests, with males also recording
      significantly (p < 0.005) higher scores in all of the strength tests than
      females. Similarly, approximately 40% of the female participants, compared to 6%
      of males, achieved an overall test "Pass" and yet gained a ranked score of 0 in
      at least three of the component tests. CONCLUSIONS: It was concluded that the
      scoring system did not exclude participants with poor fitness levels, as many
      participants recorded low scores in several test components yet still passed the
      test. We recommend that before redesigning the HRFT, studies should be first
      conducted on the occupational demands and physical standards required for this
      important profession.

PMID- 24134626
TI  - Will droplet digital PCR become the test of choice for detecting and quantifying
      ocular Chlamydia trachomatis infection? Maybe not.
AB  - Evaluation of: Roberts CH, Last A, Molina-Gonzalez S et al. Development and
      evaluation of a next-generation digital PCR diagnostic assay for ocular chlamydia
      trachomatis infections. J. Clin. Microbiol. 51(7), 2195-2203 (2013). Trachoma is
      the leading infectious cause of blindness in developing countries. Currently,
      there is no program to eliminate blinding trachoma as a public health problem. We
      need better diagnostic tests for research and to assess progress in control
      programs. Roberts et al. adapted droplet digital PCR (ddPCR), an emulsion PCR
      process that performs absolute quantitation of nucleic acids, to detect and
      quantify Chlamydia trachomatis infections. They compared the results with ddPCR
      on conjunctival swab specimens collected in trachoma-endemic area to results
      using Roche's Amplicor(r) C. trachomatis/Neisseria gonorrhoeae (CT/NG) PCR and
      found that ddPCR sensitivity was 73.3%. The authors concluded that 'ddPCR is an
      effective diagnostic technology suitable for both research and clinical use in
      diagnosing ocular C. trachomatis infections'. This reviewer disagrees, feeling
      that if the stated sensitivity is accurate, it is too low, and suggests there may
      be good reasons to adapt commercially available tests for this purpose.

PMID- 24134627
TI  - Mortality after pediatric kidney transplantation in England--a population-based
      cohort study.
AB  - The aim of this study was to explore mortality after pediatric kidney
      transplantation in England over the last decade. We used data from HES to select
      all kidney transplant procedures performed in England between April 2001 and
      March 2012. Data linkage analysis was performed with the ONS to identify all
      deaths occurring among this study cohort. Data for 1189 pediatric recipients were
      compared to 17 914 adult recipients (number of deaths, 33 vs. 2052, respectively,
      p < 0.001), with median follow-up 4.4 yr (interquartile range 2.2-7.3 yr). There
      was no difference in mortality within the pediatric cohort; age 0-1 (n = 25,
      patient survival 100.0%), age 2-5 (n = 198, patient survival 96.0%), age 6-12 (n
      = 359, patient survival 97.5%), and age 13-18 (n = 607, patient survival 97.4%),
      respectively (p = 0.567). The most common causes of death were renal (n = 8,
      24.2%), infection (n = 6, 18.2%), and malignancy (n = 5, 15.2%). All deaths from
      malignancy were secondary to PTLD. In a fully adjusted Cox regression model, only
      white ethnicity was significantly associated with risk of pediatric mortality
      post-kidney transplantation (hazard ratio 2.7, 95% confidence interval [1.0-7.3],
      p = 0.047). To conclude, this population-based cohort study confirms low
      mortality after pediatric kidney transplantation with short follow-up.

PMID- 24134629
TI  - Prevalence of vitiligo among type 2 diabetic patients in an Iranian population.
AB  - BACKGROUND: Vitiligo is one of many diseases that can be found with diabetes
      mellitus. Diabetic patients have a high incidence of vitiligo compared to the
      general population. This study assesses prevalence of vitiligo in type 2 diabetic
      patients in Iran. METHODS: One thousand one hundred type 2 diabetic patients and
      1100 healthy adults were recruited in this cross-sectional study. Patients were
      evaluated for vitiligo by a dermatologist both clinically and by Wood's lamp.
      Data were analyzed using SPSS. P value <=0.05 was considered statistically
      significant. RESULTS: There was a significant difference between groups with
      respect to presence of vitiligo; 4.9% of diabetic patients had vitiligo versus
      1.8% of control group (P = 0.001). In the female group with diabetes, 5.8% had
      vitiligo, and in male diabetic patients, 3.9% had vitiligo (P = 0.057). In the
      control group, 1.8% of females and 1.8% of males had vitiligo that was equal.
      CONCLUSION: Vitiligo and diabetes may have a causal relationship. Vitiligo may
      coexist with type 2 diabetes. Therefore it is reasonable to investigate each
      patient periodically.

PMID- 24134628
TI  - Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling
      and oxidative stress in aged spontaneously hypertensive rats.
AB  - BACKGROUND: The combination of systemic arterial hypertension and diabetes
      mellitus (DM) induces greater cardiac remodeling than either condition alone.
      However, this association has been poorly addressed in senescent rats. Therefore,
      this study aimed to analyze the influence of streptozotocin-induced DM on
      ventricular remodeling and oxidative stress in aged spontaneously hypertensive
      rats (SHR). METHODS: Fifty 18 month old male SHR were divided into two groups:
      control (SHR, n = 25) and diabetic (SHR-DM, n = 25). DM was induced by
      streptozotocin (40 mg/kg, i.p.). After nine weeks, the rats underwent
      echocardiography and myocardial functional study in left ventricular (LV)
      isolated papillary muscle preparations. LV samples were obtained to measure
      myocyte diameters, interstitial collagen fraction, and hydroxyproline
      concentration. Gene expression of atrial natriuretic peptide (ANP) and alpha- and
      beta-myosin heavy chain (MyHC) isoforms was evaluated by RT-PCR. Serum oxidative
      stress was assessed by measuring lipid hydroperoxide concentration and superoxide
      dismutase and glutathione peroxidase activities. STATISTICS: Student's t test or
      Mann-Whitney test, p < 0.05. RESULTS: SHR-DM presented higher blood glucose (487
      +/- 29 vs. 89.1 +/- 21.1 mg/dL) and lower body weight (277 +/- 26 vs. 339 +/- 38
      g). Systolic blood pressure did not differ between groups. Echocardiography
      showed LV and left atrial dilation, LV diastolic and relative wall thickness
      decrease, and LV systolic and diastolic function impairment in SHR-DM. Papillary
      muscle study showed decreased myocardial contractility and contractile reserve in
      SHR-DM. Myocyte diameters and myocardial interstitial collagen fraction and
      hydroxyproline concentration did not differ between groups. Increased serum pro
      oxidant activity and gene expression of ANP and beta/alpha-MyHC ratio were
      observed in DM. CONCLUSION: Diabetes mellitus induces cardiac dilation and
      functional impairment, increases oxidative stress and activates fetal gene
      program in aged spontaneously hypertensive rats.

PMID- 24134630
TI  - A pharmacological network for lifespan extension in Caenorhabditis elegans.
AB  - One goal of aging research is to find drugs that delay the onset of age
      associated disease. Studies in invertebrates, particularly Caenorhabditis
      elegans, have uncovered numerous genes involved in aging, many conserved in
      mammals. However, which of these encode proteins suitable for drug targeting is
      unknown. To investigate this question, we screened a library of compounds with
      known mammalian pharmacology for compounds that increase C. elegans lifespan. We
      identified 60 compounds that increase longevity in C. elegans, 33 of which also
      increased resistance to oxidative stress. Many of these compounds are drugs
      approved for human use. Enhanced resistance to oxidative stress was associated
      primarily with compounds that target receptors for biogenic amines, such as
      dopamine or serotonin. A pharmacological network constructed with these data
      reveal that lifespan extension and increased stress resistance cluster together
      in a few pharmacological classes, most involved in intercellular signaling. These
      studies identify compounds that can now be explored for beneficial effects on
      aging in mammals, as well as tools that can be used to further investigate the
      mechanisms underlying aging in C. elegans. 

PMID- 24134631
TI  - Yellow nail syndrome: clinical experience in a series of 21 patients.
AB  - BACKGROUND AND OBJECTIVES: The pathogenesis and the therapy of the yellow nail
      syndrome (YNS) are poorly defined. Our aim was to assess the clinical features,
      associated diseases and response to treatment of patients with YNS, to help
      clinicians to better diagnose and treat YNS patients. PATIENTS AND METHODS: We
      studied the medical records of all patients with YNS diagnosed at the Outpatient
      Nail Clinic of the University of Bologna in the last 28 years. All patients were
      re-evaluated to assess the evolution of the disease. RESULTS: We diagnosed YNS in
      21 patients; average age was 57 +/- 12.3 years at the time of diagnosis. In most
      patients YNS involved all 20 nails. Sixteen patients had chronic respiratory
      manifestations and 6 had lymphedema; 12 patients had other concomitant diseases.
      Ten of the 20 patients treated had a good nail response to systemic vitamin E 1
      200 IU/day, while other symptoms were not modified. CONCLUSIONS: YNS is a rare
      disorder in which the nail alterations are often the symptom that leads to
      medical consultation. Due to its association with potential serious comorbidity,
      physicians should be able to diagnose and order further investigations to assess
      presence of lymphedema and/or lung disease.

PMID- 24134632
TI  - Epithelioid hemangioendothelioma with extensive cystic change and CAMTA1
      rearrangement.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that has the
      ability to recur locally and metastasize. Thus, it is important to distinguish
      this tumor from other epithelioid vascular neoplasms. A 47-year-old man presented
      to our hospital with a pelvic mass with severe ischialgia and weight loss.
      Surgical resection was performed, and the mass was found to have dark red
      multiloculated cysts with hemorrhage and calcification. The histopathologic
      examination showed a central sclerotic, hypocellular zone and a peripheral
      cellular zone. Only the peripheral portion of the wall revealed nested tumor
      cells in light blue myxoid stroma. These tumors are typically composed of short
      strands or cords of bland epithelioid cells with occasional intracytoplasmic
      lumens embedded in a myxohyalinized stroma. The tumor cells were positive for
      CD31 and CD34 and negative for factor VIII-related antigen, CK (AE1/AE3) and S
      100. The tumor nuclei showed distinct break-apart signals with individual green
      and/or red signals, indicating the presence of CAMTA1 rearrangement. In this
      study, we report a case of EHE that was difficult to diagnose based on histology
      alone. Therefore, we also performed fluorescence in situ hybridization, and found
      that the tumor harbored a CAMTA1 gene rearrangement, which confirmed the
      diagnosis. 

PMID- 24134633
TI  - Demographic factors determining termination of pregnancy following the detection
      of lethal fetal malignancy.
AB  - OBJECTIVE: To identify demographic and clinical variables differentiating
      pregnant Polish women who decided to terminate the pregnancy in the case of
      lethal fetal malformation from those who preferred to continue the pregnancy in
      such a situation. STUDY DESIGN: Cross-sectional study. RESULTS: The group of
      women who decided to abort contained a higher fraction of multiparas than the
      group of patients who chose to continue their pregnancies, and was characterized
      by significantly lower mean gestational age at diagnosis of lethal fetal
      malformation. The only demographic variable approaching statistical significance
      was the presence of siblings, which was significantly more frequent amongst women
      who decided to terminate the pregnancy. CONCLUSIONS: As the decision-making
      process on pregnancy termination is multimodal, pregnant women require particular
      support in the case of detecting lethal malformation in their fetuses.

PMID- 24134634
TI  - Composition and genesis of calcium deposits in atheroma plaques.
AB  - The composition of atheromatous plaque determines its progression toward rupture
      or thrombosis. Although its histopathological structure has been widely studied,
      little attention has been paid to its structural and chemical composition and
      even less to its mineral component. Thirty-three atheromatous plaques were
      obtained by carotid thromboendarterectomy. Three types of materials were observed
      under polarized light microscopy: apatite crystals in the form of glomeruli (dark
      with plane polarized illumination and greensh with cross-polarized illumination);
      fibrous-like cholesterol (uncolored or grayish with plane-polarized
      illumination); and amorphous organic material as brownish deposits. SEM-EDX
      analysis showed an abundance of phosphorus and calcium in sufficient quantities
      to form calcium phosphates, and appreciably reduced levels of sodium. X-ray
      diffraction results differentiated samples into three groups: group I with
      predominance of hydroxyapatite-type crystals, group II with crystalline material
      containing an amorphous component, and group III with wholly amorphous material.
      The most abundant mineral in atheromatous plaque is hydroxyapatite, on which
      crystals of cholesterol and lipid nuclei are deposited, stratifying the plaque
      into layers that reflect the different stages of its formation. The difference in
      calcium and sodium concentrations between arteries with and without atheromata
      may indicate an important relationship in the pathophysiological development of
      calcium deposits.

PMID- 24134635
TI  - Distribution of porcine monocytes in different lymphoid tissues and the lungs
      during experimental Actinobacillus pleuropneumoniae infection and the role of
      chemokines.
AB  - Monocytes play an essential role in the defense against bacterial pathogens. Bone
      marrow (BM) and peripheral blood (PB) monocytes in pigs consist of the main
      "steady-state" subpopulations: CD14 hi/CD163-/SLA-DR- and CD14 low/CD163+/SLA
      DR+. During inflammation, the subpopulation of "inflammatory" monocytes
      expressing very high levels of CD163, but lacking the SLA-DR molecule (being CD14
      low/CD163+/SLA-DR-) appears in the BM and PB and replaces the CD14 low/CD163+/SLA
      DR+ subpopulation. However, current knowledge of monocyte migration into inflamed
      tissues in pigs is limited. The aim of the present study was to evaluate the
      distribution of "inflammatory" CD14 low/CD163+/SLA-DR- monocytes during
      experimental inflammation induced by Actinobacillus pleuropneumoniae (APP) and a
      possible role for chemokines in attracting "inflammatory" CD14 low/CD163+/SLA-DR-
      monocytes into the tissues. Monocyte subpopulations were detected by flow
      cytometry. Chemokines and chemokine receptors were detected by RT-qPCR. The
      "steady-state" monocytes were found in the BM, PB, spleen and lungs of control
      pigs. After APP-infection, "inflammatory" monocytes replaced the "steady-state"
      subpopulation in BM, PB, spleen and moreover, they appeared in an unaffected
      area, demarcation zone and necrotic area of the lungs and in tracheobronchial
      lymph nodes. They did not appear in mesenteric lymph nodes. Levels of mRNA for
      various chemokines with their appropriate receptors were found to be elevated in
      BM (CCL3-CCR1/CCR5, CCL8-CCR2/CCR5, CCL19-CCR7), necrotic area of the lungs (CCL3
      CCR1, CCL5-CCR1/CCR3, CCL11-CCR3, CCL22/CCR4) and tracheobronchial lymph nodes
      (CCL3-CCR1) and therefore they could play a role in attracting monocytes into
      inflamed tissues. In conclusion, "inflammatory" monocytes appear in different
      lymphoid tissues and the lungs after APP infection in pigs. Various chemokines
      could drive this process.

PMID- 24134636
TI  - A list of highly influential biomedical researchers, 1996-2011.
AB  - We have generated a list of highly influential biomedical researchers based on
      Scopus citation data from the period 1996-2011. Of the 15,153,100 author
      identifiers in Scopus, approximately 1% (n=149,655) have an h-index >=20. Of
      those, we selected 532 authors who belonged to the 400 with highest total
      citation count (>=25,142 citations) and/or the 400 with highest h-index (>=76).
      Of those, we selected the top-400 living core biomedical researchers based on a
      normalized score combining total citations and h-index. Another 62 authors whose
      focus is outside biomedicine had a normalized score that was at least as high as
      the score of the 400th core biomedical researcher. We provide information on the
      profile of these most influential authors, including the most common Medical
      Subject Heading terms in their articles that are also specific to their work,
      most common journals where they publish, number of papers with over 100 citations
      that they have published as first/single, last, or middle authors, and impact
      score adjusted for authorship positions, given that crude citation indices and
      authorship positions are almost totally orthogonal. We also show for each
      researcher the distribution of their papers across 4 main levels (basic-to
      applied) of research. We discuss technical issues, limitations and caveats,
      comparisons against other lists of highly-cited researchers, and potential uses
      of this resource. 

PMID- 24134637
TI  - Guided growth of epitaxially coherent GaN nanowires on SiC.
AB  - We report the guided growth of highly coherent, horizontal GaN nanowires (NWs) on
      atomically flat singular SiC (0001) and on periodically stepped vicinal SiC
      (0001) substrates. On singular SiC (0001) the NWs grow in six symmetry-equivalent
      directions, while on vicinal SiC (0001) the NWs grow only in the two directions
      parallel to the atomic step edges. All of the NWs have the same epitaxial
      relations with the substrate on both singular and vicinal (0001). Owing to the
      low mismatch (~3.4%) with the substrate, the NWs grow highly coherent, with a
      much lower density of misfit dislocations than previously observed on sapphire.
      This is also the first observation of NW VLS growth along atomic steps.
      Epitaxially coherent guided NWs have potential uses in many fields, including
      high-power electronics, light-emitting diodes (LEDs), and laser diodes.

PMID- 24134638
TI  - Mechanistic investigation and reversible effect of 2-isopropyl-5-methylcyclohexyl
      heptanoate on the in vitro percutaneous absorption of indomethacin.
AB  - In the present study, the enhancing effect of 2-isopropyl-5-methylcyclohexyl
      heptanoate (M-HEP) on the percutaneous absorption of indomethacin (IM) was
      evaluated by the in vitro penetration experiments using the rat abdominal skin as
      a barrier. Partition experiment, attenuated total reflection-Fourier transform
      infrared (ATR-FTIR) spectrum and transepidermal water loss (TEWL), was employed
      to investigate the possible mechanisms of the action of M-HEP. Furthermore, the
      reversible effect of M-HEP on excised rat skin was also evaluated through in
      vitro permeation as a preliminary indicator of safety. The result of in vitro
      permeation experiment indicated that, 10% (w/w) M-HEP in combination with
      isopropyl palmitate (IPP) significantly increased (p < 0.05), the cumulative
      amount of IM in comparison with the control group (IPP only). The partition
      coefficient of IM between the stratum corneum (SC) and enhancer solution was also
      greater than that between the SC and IPP. A blue shift in the ATR-FTIR spectra of
      SC after treatment with M-HEP solution was observed at the CH(2) band, which
      indicating that M-HEP disrupted the intercellular lipid structure of the SC. In
      addition, both M-HEP/IPP and L-menthol (MT)/IPP improved the TEWL value of rat
      abdominal skin. After removal of M-HEP, the skin barrier function would be
      restored in 8 h. In conclusion, M-HEP could reversibly enhance the percutaneous
      absorption of IM by increasing the partitioning of IM into the SC from enhancer
      solution and disturbing the organized structure of SC lipids and the
      reversibility of M-HEP was better than MT.

PMID- 24134640
TI  - Cross-coupling reactions involving metal carbene: from C?C/C-C bond formation to
      C-H bond functionalization.
AB  - Cross-coupling reactions involving metal-carbene are emerging as a new type of
      carbon-carbon bond-forming reaction. The aim of this JOCSynopsis is to provide an
      overview of the most recent development of these reactions, focusing on the use
      of diazo compounds (or in situ formed diazo compounds from N-tosylhydrazones) as
      carbene precursors. In addition, the integration of this type of reaction with C
      H bond functionalization is also surveyed. 

PMID- 24134639
TI  - Autecological traits determined two evolutionary strategies in Mediterranean
      plants during the Quaternary: low differentiation and range expansion versus
      geographical speciation in Linaria.
AB  - The evolutionary patterns of the Mediterranean flora during the Quaternary have
      been relatively well documented based on phylogenetic and biogeographic analyses,
      but few studies have addressed the evolutionary traits that determined
      diversification and range expansion success during this period. We analysed
      previously published and newly generated sequences of three plastid noncoding
      regions (rpl32-trnL(UAG) , trnS-trnG and trnL-trnF), the nuclear ribosomal
      internal transcribed spacer (ITS) and a low-copy nuclear gene intron (AGT1) of
      Linaria sect. Supinae, a group of angiosperms that diversified in the Quaternary.
      The origin and recent colonization dynamics of closely related lineages were
      inferred by biogeographic reconstruction and phylogeographic analyses, while
      breeding system experiments coupled with ecological and morphological data were
      used to test association with range expansion and diversification. A combination
      of traits, including selfing, short lifespan and the ability to tolerate a wide
      variety of substrates, were key factors underlying range expansion after long
      distance dispersal throughout the Mediterranean basin. By contrast, self
      incompatibility may have promoted higher diversification rates in narrow ranges
      of the Iberian Peninsula. We argue that a few traits contributed to the adoption
      of two contrasting strategies that may have been predominant in the evolution of
      Mediterranean angiosperms. 

PMID- 24134641
TI  - Droplet split-and-contact method for high-throughput transmembrane electrical
      recording.
AB  - This paper describes the rapid and repetitive formation of planar lipid bilayers
      via a mechanical droplet contact method for high-throughput ion channel analysis.
      In this method, first, an aqueous droplet delivered in a lipid-in-oil solution is
      mechanically divided into two small droplets. Second, the two small droplets
      contact each other, resulting in the lipid bilayer formation. Third, an ion
      channel is immediately reconstituted into the bilayer and the transmembrane
      current signals are measured. By repeating this procedure, massive data sets of
      the channel signals can be obtained. This method allowed us to perform
      statistical analysis of alpha-hemolysin conductance (n = 256 within 30 min) and
      channel inhibition experiments by contacting different types of the droplets in a
      short time frame. 

PMID- 24134642
TI  - Paraneoplastic cerebellar degeneration associated with lymphoepithelial carcinoma
      of the tonsil.
AB  - BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a classical tumor
      associated, immune-mediated disease typically associated with gynecological
      malignancies, small-cell lung-cancer or lymphoma. CASE PRESENTATION: Here we
      present the case of a 38-year old male with an over 12 months rapidly progressive
      cerebellar syndrome. Extensive diagnostic workup revealed selective
      hypermetabolism of the right tonsil in whole-body PET. Histological examination
      after tonsillectomy demonstrated a lymphoepithelial carcinoma of the tonsil and
      the tongue base strongly suggesting a paraneoplastic cause of the cerebellar
      syndrome. To the best of our knowledge this is the first case of an association
      of a lymphoepithelial carcinoma, a rare pharyngeal tumor, with PCD. CONCLUSIONS:
      In cases of classical paraneoplastic syndromes an extensive search for neoplasms
      should be performed including whole-body PET to detect tumors early in the course
      of the disease.

PMID- 24134643
TI  - Acquired haemophilia A in hepatocellular carcinoma.

PMID- 24134644
TI  - The influence of individual, partner, and relationship factors on HIV testing in
      adolescents.
AB  - Early identification of HIV by increasing testing is a national priority;
      however, little is known about HIV testing behaviors in high school age
      adolescents. We examined the association of individual, partner, and relationship
      factors with HIV testing using a computer-assisted survey administered from 2003
      to 2006 in a community sample of 980 sexually active 14- to 17-year-olds (56%
      female, 55% Latino, 25% African American) living in a jurisdiction with a high
      AIDS burden. Twenty percent reported their first sexual encounter as having
      occurred when they were <13 years of age, 33% had had four or more lifetime
      sexual partners, 21% reported high partner HIV-risk behavior, and 428 (44%) had
      been tested for HIV. In our final regression model, independent associations with
      HIV testing included being female (OR=1.68 [1.23-2.30]), older (OR=1.41 [1.21
      1.65]), and having had four or more lifetime sexual partners (OR=2.24 [1.64
      3.05]). The strongest independent predictor of HIV testing was having high HIV
      related partner communication (OR=3.70 [2.77-4.94]). Being in a serious committed
      relationship (OR=1.39 [1.02-1.87]) was also independently associated with HIV
      testing, whereas reporting high worry about HIV/AIDS (OR=0.53 [0.40-0.71]) was
      independently negatively associated with HIV testing. High HIV/AIDS knowledge,
      high partner HIV risk behavior, and young age at first sexual encounter were not
      associated with testing. These findings suggest that, for high school aged
      adolescents, optimal strategies to promote HIV testing should look beyond
      increasing HIV/AIDS knowledge and identifying individual risk behaviors to also
      considering the role of partners and relationships and their influence on testing
      behavior.

PMID- 24134645
TI  - Endothelial progenitor cell mobilization following acute wound injury.

PMID- 24134646
TI  - Structure deformation of indium oxide from nanoparticles into nanostructured
      polycrystalline films by in situ thermal radiation treatment.
AB  - A microstructure deformation of indium oxide (In2O3) nanoparticles by an in situ
      thermal radiation treatment in nitrous oxide plasma was investigated. The In2O3
      nanoparticles were completely transformed into nanostructured In2O3 films upon 10
      min of treatment time. The treated In2O3 nanoparticle sample showed improvement
      in crystallinity while maintaining a large surface area of nanostructure
      morphology. The direct transition optical absorption at higher photon energy and
      the electrical conductivity of the In2O3 nanoparticles were significantly
      enhanced by the treatment. 

PMID- 24134647
TI  - Reducing ambulance response times using discrete event simulation.
AB  - OBJECTIVES: The objectives of this study are to develop a discrete-event
      simulation (DES) model for the Singapore Emergency Medical Services (EMS), and to
      demonstrate the utility of this DES model for the evaluation of different policy
      alternatives to improve ambulance response times. METHODS: A DES model was
      developed based on retrospective emergency call data over a continuous 6-month
      period in Singapore. The main outcome measure is the distribution of response
      times. The secondary outcome measure is ambulance utilization levels based on
      unit hour utilization (UHU) ratios. The DES model was used to evaluate different
      policy options in order to improve the response times, while maintaining
      reasonable fleet utilization. RESULTS: Three policy alternatives looking at the
      reallocation of ambulances, the addition of new ambulances, and alternative
      dispatch policies were evaluated. Modifications of dispatch policy combined with
      the reallocation of existing ambulances were able to achieve response time
      performance equivalent to that of adding 10 ambulances. The median (90th
      percentile) response time was 7.08 minutes (12.69 minutes). Overall, this
      combined strategy managed to narrow the gap between the ideal and existing
      response time distribution by 11-13%. Furthermore, the median UHU under this
      combined strategy was 0.324 with an interquartile range (IQR) of 0.047 versus a
      median utilization of 0.285 (IQR of 0.051) resulting from the introduction of
      additional ambulances. CONCLUSIONS: Response times were shown to be improved via
      a more effective reallocation of ambulances and dispatch policy. More
      importantly, the response time improvements were achieved without a reduction in
      the utilization levels and additional costs associated with the addition of
      ambulances. We demonstrated the effective use of DES as a versatile platform to
      model the dynamic system complexities of Singapore's national EMS systems for the
      evaluation of operational strategies to improve ambulance response times.

PMID- 24134648
TI  - Prevalence of low testosterone and its relationship to body mass index in older
      men with lower urinary tract symptoms associated with benign prostatic
      hyperplasia.
AB  - PURPOSE: We examined the prevalence of low testosterone (LT) and its relationship
      with body mass index (BMI) in men with lower urinary tract symptoms (LUTS)
      associated with benign prostatic hyperplasia (BPH), who were enrolled in a
      clinical trial of drug therapy, the Medical Therapy of Prostatic Symptoms (MTOPS)
      Study. MATERIALS AND METHODS: MTOPS enrolled 3047 men, and of these, 1896 had
      total testosterone (TT) measured at baseline. LT was defined as a single
      measurement of TT of <300 ng/dL. RESULTS: The overall prevalence of LT was 25.7%.
      Prevalence increased with increasing BMI; 14.7% among men who were normal weight
      (BMI <25 kg/m(2)) and 24.2% and 39.3% among overweight (BMI 25 to <30 kg/m(2)),
      and obese (baseline BMI >=30 kg/m(2)) men, respectively. CONCLUSIONS: LT was
      observed in about one in four MTOPS study participants with baseline TT
      measurements. The prevalence of LT increased markedly with increasing BMI. Our
      findings suggest a high prevalence of LT in obese men with LUTS/BPH. Physicians
      should be alert to the possibility of symptoms of hypogonadism in this
      population.

PMID- 24134649
TI  - Effects of dutasteride on lower urinary tract symptoms and general health in men
      with benign prostatic hypertroplasia and hypogonadism: a prospective study.
AB  - INTRODUCTION: We investigated the effects of the relative increase in
      testosterone by dutasteride administration in patients with benign prostatic
      hyperplasia and hypogonadism on urinary symptoms or androgen-responsive general
      health. METHODS: Seventy-six patients were enrolled, and were taking 0.5 mg
      dutasteride daily for 52 weeks. Before and after treatment, all participants
      underwent blood test, and body mass index, prostate volume (PV), bone mineral
      density (BMD), post-voiding residual (PVR) volume, and muscle volume were
      measured. All patients responded to the questionnaires: International prostatic
      symptom score (IPSS), Overactive Bladder Symptom score (OABSS). Patients were
      divided into two groups according to the increase rate of total testosterone
      (TT): group A, >=20% increase in TT level; group B, <20% increase or decrease.
      RESULTS: Baseline TT and free testosterone (FT) levels were significantly lower
      in group A than group B. Both groups showed marked improvement in PV and PVR.
      Group A showed significant improvement in IPSS and OABSS with a significant
      increase of FT level, whereas group B showed no significant change. Dutasteride
      treatment contributed to a significant increase in BMD in group A. CONCLUSIONS:
      Dutasteride treatment significantly improved urinary symptoms and BMD in patients
      with low baseline serum TT and FT levels.

PMID- 24134650
TI  - Non-pharmacological interventions and neuroplasticity in early stage Alzheimer's
      disease.
AB  - Non-pharmacological interventions have the potential to reduce cognitive decline
      and to improve psychosocial aspects in mild cognitive impairment and Alzheimer's
      dementia, and the absence of side effects makes them a favorable option also for
      preventive strategies. We provide an overview on recent studies involving
      cognitive training and reminiscence, stimulating and challenging experiences such
      as visual art and music, physical activities, and electromagnetic stimulation. We
      review findings on neuroplasticity in the aging brain and their relevance for
      cognitive improvement in patients with neurodegenerative diseases. We discuss
      cognitive reserve and possible mechanisms that drive neuroplasticity and new
      learning. Finally, we identify promising avenues for future intervention
      strategies and research, such as combinations of cognitive and pharmaceutical
      interventions, and individual strategies adapted to the disease stage and
      tailored to the needs, predispositions and preferences of patients. 

PMID- 24134652
TI  - Selective steroid oxyfunctionalisation by CYP154C5, a bacterial cytochrome P450.
AB  - BACKGROUND: Cytochrome P450 monooxygenases--able to regio- and stereoselectively
      hydroxylate non-activated carbon atoms--are important enzymes for the synthesis
      of valuable intermediates in the production of steroid hormones in the
      pharmaceutical industry. However, up to now only a few bacterial enzymes able to
      hydroxylate steroids have been reported. CYP154C5 from Nocardia farcinica IFM
      10152, a bacterial P450 monooxygenase, was previously shown to convert
      testosterone to 16alpha-hydroxytestosterone. Since the hydroxylation at 16alpha
      position is of special interest for the pharmaceutical industry, we have studied
      this enzyme in more detail to investigate its activity and selectivity in
      bioconversions of further steroids. RESULTS: CYP154C5 was coexpressed in
      Escherichia coli together with putidaredoxin and putidaredoxin reductase from
      Pseudomonas putida as redox partners for electron transfer and applied in
      bioconversions of various pregnanes and androstanes [pregnenolone (1),
      dehydroepiandrosterone (2), progesterone (3), androstenedione (4), testosterone
      (5) and nandrolone (6)]. Structure elucidation of the formed products revealed an
      exclusive regio- and stereoselectivity of CYP154C5, always yielding the
      corresponding 16alpha-hydroxylated steroids. Application of whole cells
      expressing the three components, P450, Pdx and PdR, in steroid biotransformations
      resulted in significantly higher conversions and total turnover numbers (TTN)
      compared to reactions using cell-free extracts. Additionally, considerably higher
      substrate loads (up to 15 mM) were tolerated by the whole-cell system.
      Furthermore, turnover numbers (TON) were determined for the six different
      steroids using whole cells. Thus, testosterone was found to be the worst
      substrate with a TON of only 0.8 MUmol substrate consumed min-1 MUmol(-1)
      CYP154C5, while progesterone and pregnenolone were converted the fastest
      resulting in TON of 3.3 MUmol substrate consumed min(-1) MUmol(-1) CYP154C5.
      CONCLUSION: CYP154C5 from N. farcinica constitutes a promising catalyst due to
      its high regio- and stereoselectivity in the hydroxylation of different steroids
      as well as its efficient expression in E. coli at high yields. Using this enzyme,
      16alpha-hydroxylated steroids, which are important precursors for the synthesis
      of high value steroidal drugs in the pharmaceutical industry, can be selectively
      produced on preparative scale with TTN (MUmol substrate consumed MUmol(-1)
      CYP154C5) exceeding 2000.

PMID- 24134651
TI  - Human protein aging: modification and crosslinking through dehydroalanine and
      dehydrobutyrine intermediates.
AB  - Nonenzymatic post-translational modification (PTM) of proteins is a fundamental
      molecular process of aging. The combination of various modifications and their
      accumulation with age not only affects function, but leads to crosslinking and
      protein aggregation. In this study, aged human lens proteins were examined using
      HPLC-tandem mass spectrometry and a blind PTM search strategy. Multiple thioether
      modifications of Ser and Thr residues by glutathione (GSH) and its metabolites
      were unambiguously identified. Thirty-four of 36 sites identified on 15 proteins
      were found on known phosphorylation sites, supporting a mechanism involving
      dehydroalanine (DHA) and dehydrobutyrine (DHB) formation through beta-elimination
      of phosphoric acid from phosphoserine and phosphothreonine with subsequent
      nucleophilic attack by GSH. In vitro incubations of phosphopeptides demonstrated
      that this process can occur spontaneously under physiological conditions.
      Evidence that this mechanism can also lead to protein-protein crosslinks within
      cells is provided where five crosslinked peptides were detected in a human
      cataractous lens. Nondisulfide crosslinks were identified for the first time in
      lens tissue between betaB2- & betaB2-, betaA4- & betaA3-, gammaS- & betaB1-, and
      betaA4- & betaA4-crystallins and provide detailed structural information on in
      vivo crystallin complexes. These data suggest that phosphoserine and
      phosphothreonine residues represent susceptible sites for spontaneous breakdown
      in long-lived proteins and that DHA- and DHB-mediated protein crosslinking may be
      the source of the long-sought after nondisulfide protein aggregates believed to
      scatter light in cataractous lenses. Furthermore, this mechanism may be a common
      aging process that occurs in long-lived proteins of other tissues leading to
      protein aggregation diseases. 

PMID- 24134653
TI  - Synthesis of hapten and development of immunoassay based on monoclonal antibody
      for the detection of Dufulin in agricultural samples.
AB  - An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was
      developed for the quantitative detection of the antiviral agent against tobacco
      mosaic virus (TMV). Hapten 6-[2-((methyllbenzothiazol-2-yl)-1-(2-ethoxy)-O, O
      diethyl-alpha-aminophosphonate)acetamido)] hexanoic acid (DHS) was prepared from
      commercial chemicals and incorporated into the spacer arm through a carbon-carbon
      single bond. The prepared hapten was then coupled to carrier proteins keyhole
      limpet hemocyanin (KLH) to be used as an immunogen for monoclonal antibody (mAb)
      production together with ELISA development. This assay was further optimized by
      the assessment of the dependence of assay parameters on organic solvents, pH, and
      ionic strength. The IC50 values of the optimized assay for Dufulin and the
      calculated limit of detection in phosphate-buffered saline (PBS) were 9.6 +/-
      0.59 and 0.3 +/- 0.05 ng/mL, respectively. Using the optimized assays Dufulin
      residues in soil and tobacco samples were determined with recovery values ranging
      from 81.5 to 95.3%, intra-assay variation ranging from 2.88 to 6.10%, and
      interassay variation ranging from 6.11 to 9.42%. 

PMID- 24134654
TI  - Cardiovascular risk factors in children after kidney transplantation--from short
      term to long-term follow-up.
AB  - Cardiovascular-related mortality is 100-fold higher in pediatric renal transplant
      recipients than in the age-matched general population. Seventy-seven post-renal
      transplant children's charts were reviewed for cardiovascular risk factors at two
      and six months after transplantation (short term) and at two yr after
      transplantation and the last follow-up visit (mean 7.14 +/- 3.5 yr) (long term).
      Significant reduction was seen in cardiovascular risk factors prevalence from two
      months after transplantation to last follow-up respectively: Hypertension from
      52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from
      50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3%
      and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8%
      at short term to 15%. There was an increase in the prevalence of obesity from
      1.5% to 3.9% and of CKD 3-5 from 4.75% to 24%. The need for antihypertensive
      treatment decreased from 54% to 42%, and the percentage of patients controlled by
      one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3,
      and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children
      after renal transplantation appear to have high rates of cardiovascular risk
      factors, mainly on short-term follow-up.

PMID- 24134655
TI  - Fetal lung interstitial tumor: the first Japanese case report and a comparison
      with fetal lung tissue and congenital cystic adenomatoid malformation/congenital
      pulmonary airway malformation type 3.
AB  - Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was
      first reported in 2010. Here, we report the first Japanese case of fetal lung
      interstitial tumor which was originally diagnosed as atypical congenital cystic
      adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7-day
      old girl was referred to our hospital with respiratory distress and a left lung
      mass and she subsequently underwent left lower lobectomy. The specimen showed a 5
      cm solid mass with a fibrous capsule. Histological examination revealed immature
      airspaces and interstitium, containing bronchioles and cartilage. The epithelial
      and interstitial cells contained abundant glycogen granules. Immunohistochemistry
      showed nuclear/cytoplasmic expression of beta-catenin in the epithelial and
      interstitial cells. beta-catenin gene mutations and trisomy 8 were not detected,
      so a neoplastic origin could not be confirmed. The histological findings were
      partly consistent with normal fetal lung at the canalicular stage, pulmonary
      interstitial glycogenosis, and congenital cystic adenomatoid
      malformation/congenital pulmonary airway malformation type 3. In this report, we
      compare the above conditions and discuss the pathogenesis of fetal lung
      interstitial tumor.

PMID- 24134656
TI  - Preparation of ferric ion crosslinked acrylamide grafted poly (vinyl
      alcohol)/sodium alginate microspheres and application in controlled release of
      anticancer drug 5-fluorouracil.
AB  - Ionically crosslinked microspheres of acrylamide (AAm) grafted poly (vinyl
      alcohol) (PVA)/sodium alginate (NaAlg) were prepared by crosslinking with FeCl3
      and 5-fluorouracil (5-FU), which is an anticancer drug and was successfully
      encapsulated into the microspheres. The graft copolymer (PVA-g-PAAm) was
      characterized by using Fourier transform infrared spectroscopy (FTIR) and
      elemental analysis. The prepared microspheres were characterized by FTIR and
      scanning electron microscopy (SEM). Microspheres were also characterized by
      particle diameter, equilibrium swelling values and release profiles. The release
      studies were carried out at three pH values 1.2, 6.8 and 7.4, respectively, each
      for 2 h. The effects of preparation conditions as PVA-g-PAAm/NaAlg ratio,
      drug/polymer ratio, crosslinker concentration and exposure time to FeCl3 on the
      release of 5-FU were investigated for 6 h at 37  degrees C. The highest 5-FU
      release was found to be as 99.57% (w/w) at the end of 6 h for PVA-g-PAAm/NaAlg
      ratio of 1:4 (w/w), drug/polymer ratio of 1:8 (w/w), crosslinker concentration of
      0.05 M and exposure time of 10 min. The release results were also supported by
      the swelling measurements of the microspheres. Release kinetics was described by
      Fickian and non-Fickian approaches.

PMID- 24134657
TI  - Mycophenolic acid attenuates the tumour necrosis factor-alpha-mediated
      proinflammatory response in endothelial cells by blocking the MAPK/NF-kappaB and
      ROS pathways.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) has beneficial effects in cardiac
      transplant patients beyond the suppression of tissue rejection. Moreover,
      mycophenolic acid (MPA), its active metabolite, has been associated with positive
      effects on atherosclerosis in animal models. The attachment of leukocytes to the
      vascular endothelium and the subsequent migration of these cells into the vessel
      wall are early events in inflammation and atherosclerosis. The aim of this study
      was to investigate the effects of MPA on tumour necrosis-alpha (TNF-alpha)
      induced, endothelial cell proinflammatory responses and the underlying
      mechanisms. METHODS AND RESULTS: Human aortic endothelial cells (HAECs) were
      treated with different concentrations (primarily 50 MUM) of MPA before treatment
      with TNF-alpha. The surface protein and mRNA expressions of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were
      determined by flow cytometry and real-time RT-PCR, respectively. Adhesion of
      leukocytes to TNF-alpha-treated HAECs was evaluated by an adhesion assay.
      Activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB
      (NF-kappaB) was evaluated by measuring the levels of their phosphorylation using
      flow cytometry. NF-kappaB p65 translocation was detected by Western blotting. The
      production of reactive oxygen species (ROS) was determined by reduction in
      fluorescent 2',7'-dichlorofluorescein diacetate (H2 DCFH-DA). MPA significantly
      inhibits TNF-alpha-induced ICAM-1, VCAM-1 surface protein and mRNA expression as
      well as adhesion of mononuclear leukocytes to HAEC. ICAM-1 and VCAM-1 expressions
      were also reduced by antioxidants such as pyrrolidine dithiocarbamate,
      diphenylene iodonium and apocynin. MPA inhibited TNF-alpha-stimulated ROS
      generation similarly to apocynin. TNF-alpha increased ICAM-1 and VCAM-1
      expression via c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated
      kinase (ERK1/2) and p38 MAPK. MPA and apocynin inhibited TNF-alpha-induced
      phosphorylation of all three MAP kinases. Furthermore, TNF-alpha-induced NF
      kappaB activation was attenuated by SP600125 (JNK inhibitor), PD98059 (ERK1/2
      inhibitor, SB203580 (p38 MAPK inhibitor) and MPA. MPA also inhibited TNF-alpha
      induced nuclear translocation of NF-kappaB p65. CONCLUSION: These results suggest
      that, in addition to the prevention of rejection, MPA may be a promising approach
      for the treatment of inflammatory vascular disease.

PMID- 24134658
TI  - Evaluating bandgap distributions of carbon nanotubes via scanning electron
      microscopy imaging of the Schottky barriers.
AB  - We show that the Schottky barrier at the metal-single walled carbon nanotube
      (SWCNT) contact can be clearly observed in scanning electron microscopy (SEM)
      images as a bright contrast segment with length up to micrometers due to the
      space charge distribution in the depletion region. The lengths of the charge
      depletion increase with the diameters of semiconducting SWCNTs (s-SWCNTs) when
      connected to one metal electrode, which enables direct and efficient evaluation
      of the bandgap distributions of s-SWCNTs. Moreover, this approach can also be
      applied for a wide variety of semiconducting nanomaterials, adding a new function
      to conventional SEM. 

PMID- 24134659
TI  - Safety, tolerability, and pharmacokinetics of 6-month daily dosing of an oral
      formulation of cyclosporine (ATOPICA for cats(r)) in cats.
AB  - Cyclosporine was proven efficacious in the treatment of feline hypersensitivity
      dermatitis. This target animal study was conducted to evaluate the safety,
      tolerability, and pharmacokinetics of ATOPICA for Cats(r) (cyclosporine oral
      solution, USP) MODIFIED following 6-month daily dosing in cats. Forty healthy
      cats (four cats/sex/group) received 0, 8 (1*), 16 (2*), 24 (3*), or 40 (5*) mg/kg
      cyclosporine once daily for 6 months (183 days). Body weight, food consumption,
      ophthalmoscopic, physical examinations including neurological assessments, blood
      pressure, electrocardiography, clinical pathology (hematology, coagulation,
      clinical chemistry, urinalysis), organ weights, and macroscopic and microscopic
      examinations were performed and assessed. In addition, blood concentrations of
      cyclosporine were measured at the pretreatment trough on Days 1, 2, 7, 14, 31,
      91, 154, and 182, and post-treatment on Days 1, 31, and 182. Adverse effects
      possibly related to treatment included prolonged APTT and one report each of bone
      marrow hypocellularity and lymphoma; all occurred in cats treated with doses more
      than 16 mg/kg. There was no significant accumulation of cyclosporine beyond the
      first week of treatment. Results confirm that ATOPICA for Cats is safe and well
      tolerated in cats without unexpected accumulation beyond the first week of
      treatment when administered as directed.

PMID- 24134660
TI  - Histological and biochemical effects of dexmedetomidine on liver during an
      inflammatory bowel disease.
AB  - Inflammation in the liver is an extraintestinal manifestation that is frequently
      seen during inflammatory bowel diseases (IBD). The authors investigated
      histopathologycal, ultrastructural and antioxidant effects of dexmedetomidine
      (Dex) on liver during trinitrobenzene sulfonic acid (TNBS)-induced inflammatory
      bowel disease. Thirty-two BALB/c mice were divided (n = 8) as follows: control;
      Dex (dexmedetomidine) (30 MUg/kg) for 6 days; TNBS 150 MUL, TNBS + ethanol (50%
      w/v) intrarectally; TNBS + Dex. The histopathological and ultrastructural changes
      were evaluated. The levels of malondialdehyde (MDA), activity of antioxidant
      enzymes (GPx and SOD) were measured in liver tissue. Induction of colitis induced
      histopathological and ultrastructural changes of damage in liver. Those changes
      were markedly reduced in the TNBS + Dex group and that reduction was even
      significant in comparison to the TNBS group. MDA levels were significantly higher
      in the TNBS group and dexmedetomidine significantly elevated SOD levels in the
      TNBS + Dex group. These results suggest that the administration of
      dexmedetomidine reduces the histopathological and ultrastructural damage and
      increases the defense capacity against oxidative damage on liver in this IBD mice
      model.

PMID- 24134661
TI  - Sleep patterns are associated with common illness in adolescents.
AB  - This prospective, field-based study examined the association between
      actigraphically measured total sleep time and incident illness including cold,
      flu, gastroenteritis and other common infectious diseases (e.g., strep throat) in
      adolescents during the course of a school semester. Participants were 56
      adolescents ages 14-19 years (mean = 16.6, standard deviation = 1.2, 39% male)
      from five high schools in Rhode Island. Beginning in late January, adolescents
      wore actigraphs [mean 91 (19) days, range 16-112 days] and were assigned post-hoc
      to longer or shorter sleep groups based on median splits. Adolescents were
      interviewed weekly across as many as 16 weeks (modal number of interviews = 13)
      using a structured protocol that included 14 health event questions. Illness
      events and illness-related school absences were coded for 710 completed
      interviews, with 681 illness events and 90 school absences reported. Outcomes
      (illness bouts, illness duration and absences) were compared among sex, sleep and
      academic year groups using non-parametric regression. In a subset of 18 subjects,
      mean actigraphically estimated total sleep time six nights before matched
      illness/wellness events was compared using multivariate analysis of variance
      (manova). Longer sleepers and males reported fewer illness bouts; total sleep
      time effects were more apparent in males than females. A trend was found for
      shorter total sleep time before ill events. The present findings in this small
      naturalistic sample indicate that acute illnesses were more frequent in otherwise
      healthy adolescents with shorter sleep, and illness events were associated with
      less sleep during the previous week than comparable matched periods without
      illness.

PMID- 24134662
TI  - Timing and consequences of early term and late term deliveries.
AB  - OBJECTIVE: To examine the timing of elective delivery and neonatal intensive care
      unit (NICU) utilization of electively delivered infants from 2008 to 2011.
      METHODS: Analysis included 42,290 women with singleton gestation enrolled in a
      pregnancy education program, reporting uncomplicated pregnancies with elective
      labor induction (ELI) (n = 27,677) or scheduled cesarean delivery (SCD) (n =
      14,613) at 37.0-41.9 weeks' gestation. Data were grouped by type and week of
      delivery (37.0-37.9, 38.0-38.9, and 39.0-41.9 weeks). ELI and SCD for each week
      of delivery from 2008 to 2011 and nursery utilization by delivery week were
      compared. RESULTS: During the 2008-2011 timeframe, a shift in timing of ELI and
      SCD toward >=39.0 weeks was observed. In 2008, 80.9% of ELI occurred at >=39.0
      weeks versus 92.6% in 2011 (p < 0.001). In 2008, 60.5% of SCD occurred at >=39.0
      weeks versus 78.1% in 2011 (p < 0.001). NICU admission and prolonged nursery
      stays were highest at 37.0-37.9 weeks for both groups. CONCLUSIONS: We observed a
      shift toward later gestational age at elective delivery from 2008 to 2011 and
      increased NICU utilization for neonates born at <39 weeks' gestation.

PMID- 24134663
TI  - Trichosporon mucoides causing onychomycosis in an immunocompetent patient.

PMID- 24134664
TI  - Anticoccidial effects of Morinda lucida acetone extracts on broiler chickens
      naturally infected with Eimeria species.
AB  - CONTEXT: The development of drug resistance to Eimeria species in poultry is a
      reality on farms. This necessitates chemotherapeutic control alternatives, and
      plant secondary metabolities with activity is one of those potential solutions.
      OBJECTIVE: This study was designed to evaluate the efficacy of acetone leaf
      extract of Morinda lucida Benth. (Rubiaceae) against coccidiosis in broiler
      chickens. MATERIALS AND METHODS: Acute toxicity of the plant was investigated
      using 30 one-day-old broiler chicks. Anticoccidial activity investigations were
      carried out in birds drenched with 2.0, 3.0, 4.0, 5.0 and 6.0 g/kg body weight
      (BW) of acetone extract of M. lucida leaves once a day for five days, with
      toltrazuril(r) and untreated controls. The activity was evaluated by means of
      oocyst inhibition in feces, fecal score, weight gain, mortality and hematological
      parameters. RESULTS: No sign of toxicity was observed during the acute toxicity
      test. Fecal oocyst counts decreased steadily in all the treatment groups with
      time. The anticoocidial efficacy of birds treated with 2.0, 3.0, 4.0, 5.0 and 6.0
      g/kg BW of the extract was 91.2, 95.2, 98.7, 99 and 99.5%, respectively. The
      packed cell volumes, red blood cell counts and white blood cell of the treated
      birds were not significantly different (p > 0.05) from the untreated control.
      However, haemoglobin concentration and weight gain of the treated birds were
      significantly different (p < 0.05) from the untreated control. CONCLUSION: This
      study is the first to demonstrate the anticoccidial effect of M. lucida on
      Eimeria parasites. Morinda lucida leaves could therefore find application in
      anticoccidial therapy.

PMID- 24134666
TI  - Enumeration and characterization of Salmonella isolates from retail chicken
      carcasses in Beijing, China.
AB  - Epidemiological reports have implicated contaminated raw or undercooked chicken
      as primary vehicles of Salmonella transmission to human beings. Risk assessments
      relating to Salmonella contamination of poultry products in China are frequently
      hampered by the lack of quantitative data. In this study, whole chicken carcasses
      (n=395) were collected from the retail markets of Beijing, and the level of
      Salmonella contamination was enumerated by most probable number (MPN) analysis
      and all Salmonella isolates were further characterized for their serotypes and
      antimicrobial resistance. Overall, 49.9% (197/395) of the retail whole chicken
      carcasses were contaminated by Salmonella and the MPN values ranged from 1.5 to
      >550 MPN/100 g. The 50% percentile of Salmonella MPN value was 7.5 MPN/100 g in
      chicken carcass. The predominant serotypes isolated were Salmonella Enteritidis
      (n=309, 94 samples), Salmonella Indiana (n=205, 54 samples) and Salmonella
      Infantis (n=89, 23 samples). Multidrug-resistant Salmonella isolates were
      recovered from 100 chicken carcass samples; 102 isolates (from 41 chicken
      carcasses) even showed resistance to both ciprofloxacin and cefotaxime. Our
      findings showed a high prevalence of Salmonella contamination in retail chicken
      carcasses, which could be a source of exposure for consumers to multidrug
      resistant isolates. This study provided baseline enumeration data for the risk
      assessment and evaluation of new control measures of Salmonella contamination in
      retail chicken products.

PMID- 24134665
TI  - Diacylated lipopeptide from Mycoplasma synoviae mediates TLR15 induced innate
      immune responses.
AB  - Avian-specific toll like receptor 15 (TLR15) is functionally equivalent to a
      group of TLR2 family proteins that the mammalian innate immune system utilizes to
      recognize a broad spectrum of microbe-associated molecular patterns, including
      bacterial lipoproteins. In this study we examined the role of chicken TLR2 family
      members in the innate immune response to the avian pathogenic bacterium,
      Mycoplasma synoviae. We found that Mycoplasma synoviae, and specifically the N
      terminal diacylated lipopeptide (MDLP) representing the amino-terminal portion of
      its mature haemagglutinin protein, significantly induces the expression of TLR15,
      but not TLR1 and TLR2 in chicken macrophages and chondrocytes. TLR15 activation
      is specific and depends on diacylation of the lipopeptide. Activation of TLR15
      after stimulation with Mycoplasma synoviae and MDLP triggers an increase in the
      expression of transcription factor nuclear factor kappa B and nitric oxide
      production. Moreover, transfection of avian macrophage cells with small
      interfering RNA reduces the expression of TLR15 after stimulation with MDLP. This
      leads to decreased activation of the innate immune response, as measured by
      nitric oxide production. Additionally, pretreatment of cells with neutralizing
      anti-TLR15 antibody results in a notable attenuation of MDLP-driven release of
      nitric oxide. This positive correlation may constitute a mechanism for
      stimulating the innate immune response against avian mycoplasmas in chicken cells
      via TLR15.

PMID- 24134667
TI  - Challenges in listeriosis cluster and outbreak investigations, Province of
      Quebec, 1997-2011.
AB  - OBJECTIVES: Public health authorities place a high priority on investigating
      listeriosis outbreaks, and these epidemiological investigations remain
      challenging. Some approaches have been described in the literature to address
      these challenges. This review of listeriosis clusters and outbreaks investigated
      in the Province of Quebec (Quebec) highlights investigative approaches that
      contributed to identifying the source of these outbreaks. MATERIALS: The
      Laboratoire de Sante Publique du Quebec (LSPQ) implemented pulsed-field gel
      electrophoresis (PFGE) molecular subtyping in 1997 to identify Listeria
      monocytogenes clusters among isolates from invasive listeriosis cases identified
      throughout Quebec. A cluster was defined as three cases or more with the same or
      similar PFGE profiles (<=3 band difference) occurring over a 4-month period. An
      investigation was initiated if the epidemiologic indicators suggested a common
      source. Listeriosis data from LSPQ's database were reviewed to identify and
      describe clusters detected from 1997 to 2011, including those that led to an
      outbreak investigation. Epidemiological reports prepared following each outbreak
      were also reviewed. RESULTS: Eleven clusters were identified in the province by
      LSPQ between 1997 and 2011. Outbreak investigations were initiated for six
      clusters, four of which involved more than 10 cases. Factors that contributed to
      identifying the source for three of these outbreaks highlighted the value of (1)
      making all stakeholders (food safety and inspection services, public health
      authorities, and laboratories) aware of any ongoing investigation and sharing
      relevant information even if the source is not yet identified; (2) promptly
      collecting food samples identified and considered as possible vehicles of
      infection identified during the interview of a Listeria case; (3) collecting food
      items and/or environmental samples in locations reported in common by cases in
      the same cluster. CONCLUSIONS: Multiple approaches should be considered when
      investigating L. monocytogenes clusters. Networks to facilitate continuous
      exchange of human and food data between public health and food safety partners
      should be encouraged.

PMID- 24134668
TI  - Antimicrobial resistance trends among Escherichia coli isolates obtained from
      dairy cattle in the northeastern United States, 2004-2011.
AB  - Monitoring antimicrobial resistance trends among bacteria isolated from food
      animals and people is necessary to inform risk analyses and guide public policy
      regarding antimicrobial use. Our objectives were to describe the antimicrobial
      resistance status of Escherichia coli isolates from dairy cattle in the
      northeastern United States and to identify trends in resistance to selected
      antimicrobial agents over time. We collected data retrospectively for all bovine
      E. coli isolates that were obtained from samples submitted to Cornell
      University's Animal Health Diagnostic Center between January 1, 2004 and December
      31, 2011. We investigated temporal trends in the prevalence of resistant E. coli
      for each antimicrobial agent using the Cochran-Armitage trend test. Antimicrobial
      susceptibility testing was performed on 3373 bovine E. coli isolates from
      clinical samples submitted during the study period. Overall resistance to each
      antimicrobial agent ranged from 2.7% (enrofloxacin) to 91.3% (oxytetracycline).
      There was evidence of a significantly decreasing trend in prevalence of
      resistance to several agents: chlortetracycline, florfenicol, neomycin,
      oxytetracycline, spectinomycin, and trimethoprim/sulfamethoxazole. However, a
      significantly increasing trend in prevalence of resistance to enrofloxacin was
      also evident. These results do not support the idea that current antimicrobial
      use practices on dairy operations are driving a general increase in the emergence
      and dissemination of drug-resistant E. coli in the region served by the
      laboratory. However, resistance to some drugs remained consistently high during
      the study period, and increasing resistance to enrofloxacin is a key area of
      concern.

PMID- 24134669
TI  - Altered TGF-beta signaling in fetal fibroblasts: what is known about the
      underlying mechanisms?
AB  - Scarless wound healing is a unique and intrinsic capacity of the fetal skin that
      is not fully understood. Further insight into the underlying mechanisms of fetal
      wound healing may lead to new therapeutic approaches promoting adult scarless
      wound healing. Differences between fetal and adult wound healing are found in the
      extracellular matrix, the inflammatory reaction and the levels of growth factors
      present in the wound. This review focuses specifically on transforming growth
      factor beta (TGF-beta), as this growth factor is prominently involved in wound
      healing and fibroblast-to-myofibroblast differentiation. Although fetal
      fibroblasts do respond to TGF-beta, they lack a proliferative and a contractile
      response and display short-lived myofibroblast differentiation, autocrine
      response, and collagen up-regulation in comparison with adult fibroblasts.
      Curiously, prolonged TGF-beta activation is associated with fibrosis, and
      therefore, this short-lived response in fetal fibroblasts might contribute to
      scarless healing. This review gives an overview of the current knowledge on TGF
      beta signaling and the intracellular TGF-beta signaling pathway in fetal
      fibroblasts. Furthermore, this review also describes the various components that
      regulate the cellular TGF-beta response and hypothesizes about the possible roles
      these components might play in the altered response of fetal fibroblasts to TGF
      beta. 

PMID- 24134670
TI  - Variations in the phytochemical contents and antioxidant capacity of organically
      and conventionally grown Italian cauliflower (Brassica oleracea L. subsp.
      botrytis): results from a three-year field study.
AB  - A three-year field study (2009-2011) was performed to evaluate phytochemicals and
      antioxidant capacities of two genotypes (HF1 Emeraude and the local variety,
      Velox) of green cauliflower grown under organic and conventional management. The
      conventional system increased yield, but had little effect on the dry matter,
      whereas the organic system increased the soluble solids. Phytochemicals and
      antioxidant capacity showed significant year-to-year variability. During the
      third year, the scarce rainfall determined a significant increase of total
      glucosinolates and a general decrease of antioxidants in all samples.
      Interestingly, in the same year organic plants were less affected by the
      unfavorable climatic conditions, as they increased ascorbic acid, polyphenols,
      and carotenoids with respect to conventional ones. The overall results for the
      three years showed that the two genotypes responded differently. Compared to the
      conventional system, Velox showed 24, 21, 13, 48, and 44% higher content of
      ascorbic acid, polyphenols, carotenoids, volatiles, and antioxidant capacity,
      respectively. In contrast, no significant increase in the phytochemicals or the
      antioxidant potential was found in organic Emeraude, with the exception of total
      volatiles (+41%). These findings suggest that organic cultivation may be highly
      effective for particular cauliflower genotypes. 

PMID- 24134671
TI  - Volume quantification by contrast-enhanced ultrasound: an in-vitro comparison
      with true volumes and thermodilution.
AB  - BACKGROUND: Contrast-enhanced ultrasound (CEUS) has recently been proposed as a
      minimally- invasive, alternative method for blood volume measurement. This study
      aims at comparing the accuracy of CEUS and the classical thermodilution
      techniques for volume assessment in an in-vitro set-up. METHODS: The in-vitro set
      up consisted of a variable network between an inflow and outflow tube and a
      roller pump. The inflow and outflow tubes were insonified with an ultrasound
      array transducer and a thermistor was placed in each tube. Indicator dilution
      curves were made by injecting indicator which consisted of an ultrasound-contrast
      agent diluted in ice-cold saline. Both acoustic intensity- and thermo-dilution
      curves were used to calculate the indicator mean transit time between the inflow
      and outflow tube. The volumes were derived by multiplying the estimated mean
      transit time by the flow rate. We compared the volumes measured by CEUS with the
      true volumes of the variable network and those measured by thermodilution by
      Bland-Altman and intraclass-correlation analysis. RESULTS: The measurements by
      CEUS and thermodilution showed a very strong correlation (rs = 0.94) with a
      modest volume underestimation by CEUS of -40 +/- 28 mL and an overestimation of
      84 +/- 62 mL by thermodilution compared with the true volumes. Both CEUS and
      thermodilution showed a high statistically significant correlation with the true
      volume (rs = 0.97 (95% CI, 0.95 - 0.98; P<0.0001) and rs = 0.96 (95% CI, 0.94 -
      0.98; P<0.0001, respectively). CONCLUSIONS: CEUS volume estimation provides a
      strong correlation with both the true volumes in-vitro and volume estimation by
      thermodilution. It may therefore represent an interesting alternative to the
      standard, invasive thermodilution technique.

PMID- 24134672
TI  - Partner support in a cohort of African American families and its influence on
      pregnancy outcomes and prenatal health behaviors.
AB  - BACKGROUND: We examined how two indicators of partner involvement, relationship
      type and paternal support, influenced the risk of pregnancy outcomes (preterm
      birth, low birth weight) and health behaviors (prenatal care, drug use, and
      smoking) among African American women. METHODS: Interview and medical record data
      were obtained from a study of 713 adult African American women delivering
      singletons between March 2001 and July 2004. Women were enrolled prenatally if
      they received care at one of three Johns Hopkins Medical Institution (JHMI)
      prenatal clinics or post-partum if they delivered at JHMI with late, no or
      intermittent prenatal care. Relationship type was classified as married,
      unmarried/cohabitating, or unmarried/non-cohabitating. Partner support was
      assessed using an 8-item scale and was dichotomized at the median. Differences in
      partner support by pregnancy outcome and health behaviors were assessed using
      linear regression. To assess measures of partner support as predictors of adverse
      pregnancy outcomes and health behaviors, Poisson regression was used to generate
      crude and adjusted prevalence ratios (PR) and 95% confidence intervals (CI).
      RESULTS: There were no statistically significant differences in pregnancy
      outcomes or health behaviors by relationship type or when partner support was
      examined as a continuous or categorical variable. Modeled as a dichotomous
      variable, partner support was not associated with the risk of preterm birth (PR =
      0.81, 95% CI = 0.56, 1.56), low birth weight (PR = 0.77, 96% CI = 0.48, 1.26), or
      health behaviors. CONCLUSIONS: Paternal involvement was not associated with
      pregnancy outcomes or maternal health behaviors. Attention to measurement issues
      and other factors relevant for African American women are discussed.

PMID- 24134673
TI  - Generation of disk-like domains with nanometer scale thickness in merocyanine dye
      LB film induced by hydrothermal treatment.
AB  - We have characterized the binary LB films of merocyanine dye (MS) and arachidic
      acid (C20) before and after hydrothermal treatment (HTT), which is defined as a
      heat treatment under relative humidity of 100%, focusing on the morphology
      studied by bright field (BF) microscopy and fluorescence (FL) microscopy. BF
      microscopy observation has revealed that the as-deposited MS-C20 binary LB film
      is found to emit intense red fluorescence over the whole film area by 540-nm
      excitation. Since the surface image is almost featureless, it is considered that
      the crystallite sizes of J-aggregate are less than 10 MUm. Interestingly, after
      HTT, round-shaped domains are observed in the LB systems, and the sizes are
      reaching 100 MUm in diameter. Crystallites of J-aggregate, which are bluish in
      color and emit intense red fluorescence, tend to be in the round domains. We have
      observed two different types of domains, i.e., blue-rimmed domains and white
      rimmed domains, which are postulated to be confined in the inner layers and
      located at the outermost layer, respectively. The thickness of the domains is
      equal to or less than that of the double layer of the MS-C20 mixed LB film, which
      is ca. 5.52 nm. The molecular order of MS in the J-aggregate is improved by the
      HTT process leading to the significant sharpening of the band shape together with
      the further red shift of the band (from 590 to 594 nm up to 597 to 599 nm). The
      reorganized J-band is considered to be 'apparently' isotropic owing to the random
      growth of the J-aggregate in the film plane. We consider that the lubrication
      effect by the presence of water molecules predominates in the HTT process. 

PMID- 24134674
TI  - Cellular localization and kinetics of the rice melatonin biosynthetic enzymes
      SNAT and ASMT.
AB  - Serotonin N-acetyltransferase (SNAT) and N-acetylserotonin methyltransferase
      (ASMT) are the final two enzymes in the melatonin synthesis pathway in plants.
      Although their corresponding genes have been cloned, their cellular localization
      and enzymatic characteristics are unknown. Using confocal microscopy, we showed
      that SNAT protein is localized in chloroplasts, whereas ASMT is expressed in the
      cytoplasm. In vitro measurement of ASMT enzyme activity revealed a peak of
      activity in roots, but SNAT enzyme activity was not detected in any plant
      tissues. This may be attributed in part to an effect of chlorophyll because SNAT
      enzyme activity was greatly inhibited by chlorophyll in a dose-dependent manner.
      Because the SNAT protein of cyanobacteria is thermophilic, we examined the effect
      of temperature on the activity of the rice SNAT and ASMT enzymes. Purified
      recombinant rice SNAT and ASMT enzymes had an optimum temperature for activity of
      55 degrees C. The Km and Vmax values for SNAT at 55 degrees C were 270 MUm and
      3.3 nmol/min/mg protein, whereas the Km and Vmax for ASMT were 222 MUm and 9
      nmol/min/mg protein, respectively. The catalytic efficiency (Vmax /Km ) values of
      SNAT and ASMT were 16-fold and 4054-fold higher at 55 degrees C than at 30
      degrees C suggestive of increased melatonin production at high temperature in
      plants. 

PMID- 24134675
TI  - Matrix metalloproteinase-1 promoter -1607 1G/2G polymorphism and chronic
      periodontitis susceptibility: a meta-analysis and systematic review.
AB  - AIM: Matrix metalloproteinase-1 promoter -1607 1G/2G (rs1799750) polymorphism
      have been shown to confer genetic susceptibility to chronic periodontitis (CP),
      but the results are inconsistent. MATERIALS AND METHODS: A meta-analysis and
      systematic review was performed to accomplish a more precise estimation of the
      relationship. RESULTS: Pooled estimates revealed that there was no significant
      association between this polymorphism and CP risk in Caucasian and Asian
      populations. In addition, it was reported by three Brazilian studies that no
      significant association was found for this polymorphism with CP risk in a
      Brazilian mixed population. Besides, there was no significant association of this
      polymorphism with mild to moderate and severe CP risk in both Caucasian and Asian
      populations. Moreover, both non-smokers and smokers did not have a significant
      association between this polymorphism and susceptibility to CP in Caucasian
      population. CONCLUSIONS: Matrix metalloproteinase-1 promoter -1607 1G/2G
      (rs1799750) polymorphism may have no effect on the disease susceptibility of CP
      in Caucasian, Asian and Brazilian mixed populations. Besides, this polymorphism
      may not play a direct role in severity of CP among both Caucasian and Asian
      populations, and between this polymorphism and smoking there may be no
      interactions to be associated with CP risk in Caucasian population.

PMID- 24134676
TI  - Long-term molecular remission with persistence of BCR-ABL1-specific cytotoxic T
      cells following imatinib withdrawal in an elderly patient with Philadelphia
      positive ALL.

PMID- 24134678
TI  - The role of hydrophobicity in the disruption of erythrocyte membrane by
      nanoparticles composed of hydrophobically modified poly(gamma-glutamic acid).
AB  - Polymeric nanoparticles (NPs) prepared from biocompatible polymers have been
      studied extensively as carriers for the targeted and controlled delivery of
      antigens to develop safe and effective vaccines. Especially, the endosomal escape
      of antigens is essential for the induction of antigen-specific potent immune
      responses, and the NPs which can control the endosomal escape are urgently
      required. It has been reported that the hydrophobicity of polymers affected the
      interactions between the polymer and the membranes, but there have no reports
      about investigating the effect of the hydrophobicity of the NPs on the membrane
      disruptive property. In this study, we evaluated the effect of hydrophobicity of
      NPs on the membrane disruptive property for the first time. We prepared NPs
      composed of amphiphilic poly(gamma-glutamic acid) (gamma-PGA) with various
      grafting degrees of hydrophobic backbone (43-71%), and evaluated the membrane
      disruptive property. These NPs showed membrane disruptive activity only at the
      endosomal pH range, and this activity was dependent on the hydrophobicity of
      gamma-PGA. The dependency of the membrane disruptive property on the
      hydrophobicity of NPs was due to the surface hydrophobicity of them. Our results
      could provide a guideline for the rational design of amphiphilic polymers as
      nanoparticle-based vaccine carriers. 

PMID- 24134677
TI  - H3K4 demethylase activities repress proliferative and postmitotic aging.
AB  - Homeostasis of postmitotic and proliferating cells is maintained by pathways that
      repress stress. We found that the Caenorhabditis elegans histone 3 lysine 4
      (H3K4) demethylases RBR-2 and SPR-5 promoted postmitotic longevity of stress
      resistant daf-2 adults, altered pools of methylated H3K4, and promoted silencing
      of some daf-2 target genes. In addition, RBR-2 and SPR-5 were required for germ
      cell immortality at a high temperature. Transgenerational proliferative aging was
      enhanced for spr-5; rbr-2 double mutants, suggesting that these histone
      demethylases may function sequentially to promote germ cell immortality by
      targeting distinct H3K4 methyl marks. RBR-2 did not play a comparable role in the
      maintenance of quiescent germ cells in dauer larvae, implying that it represses
      stress that occurs as a consequence of germ cell proliferation, rather than
      stress that accumulates in nondividing cells. We propose that H3K4 demethylase
      activities promote the maintenance of chromatin states during stressful growth
      conditions, thereby repressing postmitotic aging of somatic cells as well as
      proliferative aging of germ cells. 

PMID- 24134679
TI  - High-efficiency microwave-assisted digestion combined to in situ ultraviolet
      radiation for the determination of rare earth elements by ultrasonic nebulization
      ICPMS in crude oils.
AB  - A method for heavy and extraheavy crude oil digestion based on microwave-assisted
      wet digestion (MW-AD) and ultraviolet (UV) radiation using diluted HNO3 was
      applied for the determination of rare earth elements (REE) by inductively coupled
      plasma mass spectrometry (ICPMS) with an ultrasonic nebulizer (USN). Even using
      pressurized systems conventional acid digestion is not feasible for efficient
      crude oil digestion, especially for heavy and extraheavy crude oils that
      generally present high amounts of asphaltenes and resins. In the proposed system,
      UV radiation is generated in situ by immersed electrodeless Cd discharge lamps
      positioned inside quartz vessels. The use of diluted solutions (1-14.4 mol L(-1)
      HNO3 and 1-4 mol L(-1) H2O2) were evaluated for heavy and extraheavy crude oil
      digestion (API density of 11.1-19.0). With the proposed method the residual
      carbon content was lower than 13 mg C/100 mg of sample, and it was possible to
      digest sample masses up to 500 mg using 4 mol L(-1) HNO3 and 4 mol L(-1) H2O2.
      Interferences caused by excessive acid concentration and carbon content in
      digests were minimized allowing limits of quantification for REEs as low as 0.3
      ng g(-1). Samples were also digested using MW-AD in pressurized systems with
      concentrated HNO3, but even using 280  degrees C, 80 bar, and concentrated HNO3,
      MW-AD method was not suitable for REE determination due to interferences in ICPMS
      determination. The combination of microwave heating with UV was considered a
      suitable and effective way to digest crude oil allowing further determination of
      low concentrations of REE by ICPMS. 

PMID- 24134681
TI  - Multifocal and microscopic chromophobe renal cell carcinomatous lesions
      associated with 'capsulomas' without FCLN gene abnormality.
AB  - Chromophobe renal cell carcinoma (RCC) accounts for approximately 5% of renal
      epithelial neoplasms. Multiple and/or bilateral chromophobe RCCs in an individual
      are generally rare but frequently occur in patients with Birt-Hogg-Dube syndrome
      (BHDS) and in patients with tuberous sclerosis complex (TSC). The responsible
      genes in both BHDS and TSC act as tumor suppressors. Therefore, it seems that
      some genetic backgrounds are required for the generation and progression of
      multiple chromophobe RCCs. Here, we report a case of multiple and bilateral
      chromophobe RCCs along with several small-sized capsular angiomyolipomas known as
      'capsulomas' in a 39-year-old woman who had neither a particular medical history
      nor specific gene mutation. There has been no report of sporadic multiple
      chromophobe RCCs and 'capsulomas' developing in a patient without genetic
      features, having potential for novel genetic variation. 

PMID- 24134682
TI  - Gravitaxis in spherical Janus swimming devices.
AB  - In this work, we show that the asymmetrical distribution of mass at the surface
      of catalytic Janus swimmers results in the devices preferentially propelling
      themselves upward in a gravitational field. We demonstrate the existence of this
      gravitaxis phenomenon by observing the trajectories of fueled Janus swimmers,
      which generate thrust along a vector pointing away from their metallically coated
      half. We report that as the size of the spherical swimmer increases, the
      propulsive trajectories are no longer isotropic with respect to gravity, and they
      start to show a pronounced tendency to move in an upward direction. We suggest
      that this effect is due to the platinum caps asymmetric mass exerting an
      increasing influence on the azimuthal angle of the Janus sphere with size,
      biasing its orientation toward a configuration where the heavier propulsion
      generating surface faces down. This argument is supported by the good agreement
      we find between the experimentally observed azimuthal angle distribution for the
      Janus swimmers and predictions made by simple Boltzmann statistics. This
      gravitaxis phenomenon provides a mechanism to autonomously control and direct the
      motion of catalytic swimming devices and so enable a route to make autonomous
      transport devices and develop new separation, sensing, and controlled release
      applications. 

PMID- 24134683
TI  - Development and characterization of PLGA nanoparticles as delivery systems of a
      prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid.
AB  - CONTEXT: Zidovudine (AZT) is employed against AIDS and hepatitis; its use is
      limited by active efflux transporters (AETs) that induce multidrug resistance for
      intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid
      (UDCA) conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems.
      OBJECTIVE: To investigate the effect of the Pluronic F68 coating on the loading,
      release and stability of poly(D,L lactide-co-glicolide) nanoparticles (NPs)
      embedded with UDCA-AZT. MATERIALS AND METHODS: The mean diameter of the NP
      prepared by nanoprecipitation or emulsion/solvent evaporation methods was
      determined using both photon correlation spectroscopy and sedimentation field
      flow fractionation; particle morphology was detected by scanning electron
      microscope. The stability of the free and encapsulated UDCA-AZT was evaluated in
      rat liver homogenates by high-performance liquid chromatography analysis. RESULTS
      AND DISCUSSION: The mean diameter of the NPs was found to be ~ 600 nm with a
      relatively high polydispersity. The NPs obtained by emulsion/solvent evaporation
      were not able to control the prodrug release, differently from NPs obtained by
      nanoprecipitation. The presence of the Pluronic coating did not substantially
      modify the kinetics of the drug release, or the extent of the burst effect that
      were instead only influenced by the preparation parameters. UDCA-AZT incorporated
      in the NPs was more stable in the rat liver homogenates than the free prodrug and
      no influence of the Pluronic coating was observed. CONCLUSIONS: Considering the
      different potential applications of nanoparticles coated and uncoated with
      Pluronic (brain and macrophage targeting, respectively), both of these
      nanoparticle systems could be useful in the therapies against HIV.

PMID- 24134684
TI  - Dermal ultrastructure in collagen VI myopathy.
AB  - The COL VI mutations are responsible for a spectrum of myopathies. The authors
      report cutaneous ultrastructural alterations in a patient with COL6A2 myopathy.
      The changes include variations in size of collagen fibrils, flower-like sections
      of collagen fibrils, as well as thickening of vessel and nerve basement
      membranes. Electron microscopy of a skin biopsy contributes to the diagnosis of
      COL VI myopathies.

PMID- 24134685
TI  - Vertical nanowire heterojunction devices based on a clean Si/Ge interface.
AB  - Different vertical nanowire heterojunction devices were fabricated and tested
      based on vertical Ge nanowires grown epitaxially at low temperatures on (111) Si
      substrates with a sharp and clean Si/Ge interface. The nearly ideal Si/Ge
      heterojuctions with controlled and abrupt doping profiles were verified through
      material analysis and electrical characterizations. In the nSi/pGe heterojunction
      diode, an ideality factor of 1.16, subpicoampere reverse saturation current, and
      rectifying ratio of 10(6) were obtained, while the n+Si/p+Ge structure leads to
      Esaki tunnel diodes with a high peak tunneling current of 4.57 kA/cm(2) and
      negative differential resistance at room temperature. The large valence band
      discontinuity between the Ge and Si in the nanowire heterojunctions was further
      verified in the p+Si/pGe structure, which shows a rectifying behavior instead of
      an Ohmic contact and raises an important issue in making Ohmic contacts to
      heterogeneously integrated materials. A raised Si/Ge structure was further
      developed using a self-aligned etch process, allowing greater freedom in device
      design for applications such as the tunneling field-effect transistor (TFET). All
      measurement data can be well-explained and fitted with theoretical models with
      known bulk properties, suggesting that the Si/Ge nanowire system offers a very
      clean heterojunction interface with low defect density, and holds great potential
      as a platform for future high-density and high-performance electronics. 

PMID- 24134687
TI  - Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty
      liver disease.
AB  - BACKGROUND: Soluble CD36 (sCD36) clusters with insulin resistance, but no
      evidence exists on its relationship with hepatic fat content. We determined sCD36
      to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and
      chronic hepatitis C (CHC) patients. MATERIALS AND METHODS: Two hundred and twenty
      seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically
      normal liver (NL) were studied. Steatosis was graded by Kleiner's histological
      scoring system. Serum sCD36 and hepatic CD36 expression was assessed by
      immunoassay and immunohistochemistry, respectively. RESULTS: In NAFLD, serum
      sCD36 levels were significantly higher in simple steatosis than in NL (361.4 +/-
      286.4 vs. 173.9 +/- 137.4 pg/mL, respectively; P < 0.001), but not in
      steatohepatitis (229.6 +/- 202.5 pg/mL; P = 0.153). In CHC, serum sCD36 levels
      were similar regardless of the absence (428.7 +/- 260.3 pg/mL) or presence of
      steatosis (387.2 +/- 283.6 pg/mL; P = 0.173). A progressive increase in serum
      sCD36 values was found in NAFLD depending on the histological grade of steatosis
      (P < 0.001), but not in CHC (P = 0.151). Serum sCD36 concentrations were
      independently associated with advanced steatosis in NAFLD when adjusted by
      demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence
      interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002;
      95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was
      observed between hepatic CD36 and serum sCD36 (rho = 0.499, P < 0.001).
      CONCLUSIONS: Increased serum sCD36 is an independent factor associated with
      advanced steatosis in NAFLD.

PMID- 24134686
TI  - Immunology of lymphatic filariasis.
AB  - The immune responses to filarial parasites encompass a complex network of innate
      and adaptive cells whose interaction with the parasite underlies a spectrum of
      clinical manifestations. The predominant immunological feature of lymphatic
      filariasis is an antigen-specific Th2 response and an expansion of IL-10
      producing CD4(+) T cells that is accompanied by a muted Th1 response. This
      antigen-specific T-cell hyporesponsiveness appears to be crucial for the
      maintenance of the sustained, long-standing infection often with high parasite
      densities. While the correlates of protective immunity to lymphatic filariasis
      are still incompletely understood, primarily due to the lack of suitable animal
      models to study susceptibility, it is clear that T cells and to a certain extent
      B cells are required for protective immunity. Host immune responses, especially
      CD4(+) T-cell responses clearly play a role in mediating pathological
      manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main
      underlying defect in the development of clinical pathology appears to be a
      failure to induce T-cell hyporesponsiveness in the face of antigenic stimulation.
      Finally, another intriguing feature of filarial infections is their propensity to
      induce bystander effects on a variety of immune responses, including responses to
      vaccinations, allergens and to other infectious agents. The complexity of the
      immune response to filarial infection therefore provides an important gateway to
      understanding the regulation of immune responses to chronic infections, in
      general. 

PMID- 24134688
TI  - Seroconversion of 2009 pandemic influenza A (H1N1) vaccination in kidney
      transplant patients and the influence of different risk factors.
AB  - BACKGROUND: Influenza may present a high morbidity and mortality in solid organ
      transplanted patients (SOTP). Annual influenza virus vaccine is recommended for
      SOTP. However, low levels of seroconversion in SOTP have been reported. The aim
      of this study was to evaluate the immunogenicity of 2009 pandemic influenza A
      (H1N1) - A(H1N1)pdm09--vaccine in kidney transplant patients and to analyze which
      features might affect seroconversion. METHODS: This study was conducted from
      March to August 2010 at the Renal Transplantation Unit of University of Sao
      Paulo, Brazil. A total of 85 renal transplant patients attending the outpatient
      unit received one 15-MUg intramuscular dose of A(H1N1) pdm09 influenza vaccine
      (reassortant vaccine virus A/California/7/2009 [NYMC X-179A]). Blood samples were
      collected immediately before and 21 days after the vaccine was given. Antibody
      response was measured by the standard hemagglutination-inhibition (HI) assay. The
      primary immunogenicity endpoint for this study was seroconversion in previously
      seronegative patients (HI titers <1:40), and the secondary endpoint was the
      identification of features that could affect seroconversion in this population.
      RESULTS: Five (5.9%) patients presented HI titers prevaccination >= 1:40 and were
      excluded from further analysis. Seroconversion in previously negative patients
      occurred in 27 (34%) of 80 patients. Prevaccination HI titers geometrical mean
      was 5.8 and postvaccination 19.6 (ratio 3.4). Significant seroconversion rate
      factors were female gender, non-Caucasian ethnicity, and post-transplant time
      before vaccination. No impact was seen on seroconversion for age, donor type,
      tacrolimus and cyclosporine blood levels, renal function, or blood lymphocyte
      counts. Mycophenolate (MPA) showed a lower rate of seroconversion when compared
      with azathioprine. Tacrolimus and cyclosporine had similar seroconversion rates.
      Sirolimus use was associated with the highest rate of seroconversion, although
      these patient numbers were low. Immunosuppresssion containing MPA was
      considerably less effective in seroconversion than drug combinations with no MPA.
      Patients receiving sirolimus had more chance of seroconversion. HI titers
      geometric means pre/post vaccine were as follows: MPA (n = 56): 5.8/12.8;
      tacrolimus (n = 50): 5.9/16.2; cyclosporine (n = 18): 5.4/24.2; azathioprine (n =
      19): 6.2/51.6; and sirolimus (n = 6): 8/80. By univariate analysis, being female
      and non-White were variables associated with 3.3 times more chance of
      seroconversion than being male and White. In the multivariate analysis, the
      variables remaining in the model showed similar hazard ratios. CONCLUSIONS: In
      this study, the monovalent A(H1N1)pdm09 influenza vaccine demonstrated low rates
      of seroconversion, particularly in patients on MPA, but with potentially higher
      response rates in patients on sirolimus.

PMID- 24134689
TI  - Tobacco use disorder and the risk of suicide mortality.
AB  - BACKGROUND AND AIMS: Tobacco use may be a risk factor for suicide mortality;
      however, prior research has produced equivocal findings and has been limited by
      relatively small sample sizes to study the rare event of suicide, as well as a
      lack of adjustment for other important factors, including psychiatric illness. We
      estimate the predictive association between tobacco use disorder and the risk of
      suicide mortality, adjusting for other important variables. DESIGN: A prospective
      cohort study. SETTING: The United States Veterans Health Administration (VHA).
      PARTICIPANTS: All individuals who received VHA services in fiscal year (FY) 2005
      and were alive at the start of FY 2006 (n = 4 863 086). MEASUREMENTS: Tobacco use
      disorder was assessed via FYs 2004-05 VHA National Patient Care Database records.
      The outcome of suicide mortality was assessed during the follow-up interval from
      the beginning of FY 2006 to the end of FY 2008 using National Death Index
      records. FINDINGS: Of the 4 863 086 individuals in the study, 4823 died by
      suicide during the follow-up interval. In the unadjusted model, tobacco use
      disorder was associated with an increased risk of suicide [hazard ratio (HR) =
      1.88; 95% confidence interval (CI) = 1.76, 2.02]. After adjustment for model
      covariates, the association remained statistically significant, although
      attenuated (HR = 1.36, 95% CI = 1.27, 1.46). CONCLUSIONS: Tobacco use disorder
      may confer a modest excess risk of death by suicide. Psychiatric disorders may
      partially explain the relationship between tobacco use disorder and suicide.

PMID- 24134690
TI  - Live bee acupuncture (Bong-Chim) dermatitis: dermatitis due to live bee
      acupuncture therapy in Korea.
AB  - Live bee acupuncture (Bong-Chim) dermatitis is an iatrogenic disease induced by
      so-called live bee acupuncture therapy, which applies the honeybee (Apis cerana)
      stinger directly into the lesion to treat various diseases in Korea. We present
      two cases of live bee acupuncture dermatitis and review previously published
      articles about this disease. We classify this entity into three stages: acute,
      subacute, and chronic. The acute stage is an inflammatory reaction, such as
      anaphylaxis or urticaria. In the chronic stage, a foreign body granuloma may
      develop from the remaining stingers, similar to that of a bee sting reaction.
      However, in the subacute stage, unlike bee stings, we see the characteristic
      histological "flame" figures resulting from eosinophilic stimulation induced by
      excessive bee venom exposure. We consider this stage to be different from the
      adverse skin reaction of accidental bee sting. 

PMID- 24134691
TI  - The LysR-type transcription factor HbrL is a global regulator of iron homeostasis
      and porphyrin synthesis in Rhodobacter capsulatus.
AB  - The purple bacterium Rhodobacter capsulatus is unique among Rhodobacteriacae as
      it contains a putative iron response regulator (Irr) but does not possess a copy
      of the ferric uptake regulator (Fur). Interestingly, an in-frame deletion mutant
      of Irr shows no major role in iron homeostasis. Instead, we showed that the
      previously identified activator of haem gene expression HbrL is a crucial
      regulator of iron homeostasis. We demonstrated that an HbrL deletion strain is
      unable to grow in iron-limited medium in aerobic, semi-aerobic and photosynthetic
      conditions and that suppressor strains can be isolated with mutations in iron
      uptake genes. Gene expression studies revealed that HbrL is a transcriptional
      activator of multiple ferrous and ferric iron uptake systems in addition to a
      haem uptake system. Finally, HbrL activates the expression of numerous haem
      biosynthesis genes. Thus, HbrL has a central role in controlling the amount of
      iron transport in conjunction with the synthesis of its cognate tetrapyrrole
      haem. 

PMID- 24134692
TI  - Conditional over-expression of RAGE by embryonic alveolar epithelium compromises
      the respiratory membrane and impairs endothelial cell differentiation.
AB  - BACKGROUND: Receptors for advanced glycation end-products (RAGE) are cell surface
      receptors prominently expressed by lung epithelium. Previous research
      demonstrated that over-expression of RAGE by murine alveolar epithelial cells
      during embryogenesis caused severe lung hypoplasia and neonatal lethality.
      However, the effects of RAGE over-expression on adjacent matrix and endothelial
      cells remained unknown. METHODS: RAGE transgenic (TG) mice were generated that
      conditionally over-expressed RAGE in alveolar type II cells when fed doxycycline
      (dox) from conception to E18.5. To evaluate effects on the basement membrane,
      immunostaining and immunoblotting were performed for collagen IV and MMP-9, a
      matrix metalloprotease capable of degrading basement membranes. To assess changes
      in vasculature, immunostaining, immunoblotting and qRT-PCR were performed for
      Pecam-1, a platelet endothelial cell adhesion marker also known as CD31. Lastly,
      to characterize potential regulatory mechanisms of endothelial cell
      differentiation, immunoblotting and qRT-PCR for FoxM1, a key endothelium-specific
      transcription factor of the Forkhead Box (Fox) family, were completed. RESULTS:
      Qualitative immunostaining for collagen IV was less in RAGE TG mice compared to
      controls and immunoblotting revealed decreased collagen IV in the RAGE TG mouse
      lung. Additionally, elevated MMP-9 detected via immunostaining and immunoblotting
      implicated MMP-9 as a possible down stream effector in matrix destabilization
      mediated by RAGE signaling. Lastly, Pecam-1 assessment revealed a decrease in the
      prevalence of microvascular endothelial cells coincident with FoxM1 abrogation in
      RAGE TG mice compared to controls. CONCLUSIONS: RAGE over-expression by alveolar
      epithelium weakened the basement membrane and associated matrix via increased MMP
      9 activity. Furthermore, over-expression of RAGE inhibited FoxM1, suggesting that
      anomalous transcriptional control contributes to decreased endothelial cell
      prevalence in the TG mouse lung.

PMID- 24134693
TI  - Predictors of cigarette use amongst Pacific youth in New Zealand.
AB  - BACKGROUND: Despite progressive population health policies to reduce tobacco
      harm, smoking prevalence continues to be inequitable amongst key ethnic groups in
      New Zealand. The purpose of this study is to describe the predictors of cigarette
      use amongst Pacific youth in New Zealand. METHODS: Data were collected as part of
      Youth'07, a nationally representative survey of the health and well-being of New
      Zealand adolescents. The study sample comprised 5471 students and this includes
      1,178 were Pacific youth. RESULTS: The smoking prevalence rate for Pacific youth
      was twice that of New Zealand European youth. Pacific girls and older age groups,
      ages 16-17, smoked more than Pacific boys and younger adolescents. Pacific youth
      from higher and mid-deprivation neighbourhoods smoked at twice the rate of youth
      from low deprivation areas. Local neighbourhood stores (dairies) were the most
      used location for purchasing cigarettes, and only 12.7% of under-aged adolescents
      were asked "most of the time" for age identification. Pacific adolescent smoking
      was associated with parental smoking, peer-group smoking and binge drinking.
      Parents not knowing the whereabouts of adolescents during after-school hours and
      night-times were also associated with adolescent smoking. A majority of Pacific
      adolescent smokers (70.2%) had tried to quit smoking. CONCLUSION: The strategies
      for addressing ethically the issue of equal health for all is to allocate
      increased public health investments towards targeted quit-smoking treatment
      programmes for Pacific youth in New Zealand. Further qualitative studies with
      Pacific youth to inform the development of culturally-appropriate youth-focused
      quit-substance interventions is recommended.

PMID- 24134694
TI  - A prospective study of tubular dysfunction in pediatric patients with Beta
      thalassemia major receiving deferasirox.
AB  - BACKGROUND: Beta thalassemia major is a lifelong transfusion-dependent disorder.
      Transfusion-dependent thalassemia patients are prone to develop renal dysfunction
      due to iron overload, chronic anemia, and/or chelation therapy. METHODS: In this
      prospective study, thalassemia patients who fitted inclusion and exclusion
      criteria received Deferasirox 20 mg/kg/day. A complete biochemistry analysis of
      serum and 24-hour-urine specimens was performed before and after treatment.
      Estimated glomerular filtration rate (eGFR), Fractional excretion of sodium
      (FENA), potassium (FEK), uric acid (FEUA), and the maximum ratio of tubular
      reabsorption of phosphorus to eGFR (TmP/GFR) at baseline and after treatment was
      calculated and compared. RESULTS: A total of 30 patients with mean age of 4.9 +/-
      3.2 years were recruited. The mean serum creatinine increased significantly after
      6 months of treatment (0.54 +/- 0.08 vs. 0.67 +/- 0.16, P < .001) while eGFR was
      decreased (104.36 +/- 19.62 vs. 86.00 +/- 16.92, P < .001). Mean potassium level
      in serum was increased after treatment, while serum calcium, magnesium, and uric
      acid levels decreased significantly (P > .05). A significant increase was
      confirmed for mean urinary beta2-microglobulin (beta2-MG), protein, uric acid,
      calcium, and magnesium (P > .05). CONCLUSION: Our findings highlighted tubular
      nephropathy induced by Deferasirox in patients with beta thalassemia, and
      confirmed the necessity for diligent monitoring of renal function in thalassemia
      patients receiving Deferasirox.

PMID- 24134695
TI  - High-throughput screening using the differential radial capillary action of
      ligand assay identifies ebselen as an inhibitor of diguanylate cyclases.
AB  - The rise of bacterial resistance to traditional antibiotics has motivated recent
      efforts to identify new drug candidates that target virulence factors or their
      regulatory pathways. One such antivirulence target is the cyclic-di-GMP (cdiGMP)
      signaling pathway, which regulates biofilm formation, motility, and pathogenesis.
      Pseudomonas aeruginosa is an important opportunistic pathogen that utilizes
      cdiGMP-regulated polysaccharides, including alginate and pellicle polysaccharide
      (PEL), to mediate virulence and antibiotic resistance. CdiGMP activates PEL and
      alginate biosynthesis by binding to specific receptors including PelD and Alg44.
      Mutations that abrogate cdiGMP binding to these receptors prevent polysaccharide
      production. Identification of small molecules that can inhibit cdiGMP binding to
      the allosteric sites on these proteins could mimic binding defective mutants and
      potentially reduce biofilm formation or alginate secretion. Here, we report the
      development of a rapid and quantitative high-throughput screen for inhibitors of
      protein-cdiGMP interactions based on the differential radial capillary action of
      ligand assay (DRaCALA). Using this approach, we identified ebselen as an
      inhibitor of cdiGMP binding to receptors containing an RxxD domain including PelD
      and diguanylate cyclases (DGC). Ebselen reduces diguanylate cyclase activity by
      covalently modifying cysteine residues. Ebselen oxide, the selenone analogue of
      ebselen, also inhibits cdiGMP binding through the same covalent mechanism.
      Ebselen and ebselen oxide inhibit cdiGMP regulation of biofilm formation and
      flagella-mediated motility in P. aeruginosa through inhibition of diguanylate
      cyclases. The identification of ebselen provides a proof-of-principle that a
      DRaCALA high-throughput screening approach can be used to identify bioactive
      agents that reverse regulation of cdiGMP signaling by targeting cdiGMP-binding
      domains. 

PMID- 24134696
TI  - US-National Institutes of Health-funded research for cutaneous wounds in 2012.
AB  - Chronic cutaneous wounds are a major burden on patients, healthcare providers,
      and the US healthcare system. This study, carried out in part by the Wound
      Healing Society's Government Regulatory Committee, aimed to evaluate the current
      state of National Institutes of Health funding of cutaneous wound healing-related
      research projects. National Institutes of Health Research Portfolio Online
      Reporting Tools Expenditures & Results system was used to identify wound healing
      projects funded by the National Institutes of Health in the 2012 fiscal year.
      Research projects focusing on cutaneous wound prevention/education, mechanisms,
      complications, treatment, or imaging/monitoring were included in the analysis.
      Ninety-one projects were identified, totaling a collective funding of $29,798,991
      and median funding of $308,941. Thirteen institutes/centers from the National
      Institutes of Health were responsible for awarding funds; three of which
      (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
      Institute of General Medical Sciences, National Institute of Diabetes and
      Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The
      predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%).
      New applications and pre-existing applications accounted for 39.6 and 55.0% of
      the awarded grants, respectively. Grants awarded to investigators affiliated with
      universities accounted for 68.1% of grants and 25.3% were to investigators in the
      private sector. This analysis of current National Institutes of Health funding
      may facilitate more transparency of National Institutes of Health-allocated
      research funds and serve as an impetus to procure additional support for the
      field of wound healing. 

PMID- 24134697
TI  - Diabetes and hypertension increase the placental and transcellular permeation of
      the lipophilic drug diazepam in pregnant women.
AB  - BACKGROUND: Previous studies carried out in our laboratories have demonstrated
      impaired drug permeation in diabetic animals. In this study the permeation of
      diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be
      investigated in diabetic and hypertensive pregnant women. METHODS: A total 75
      pregnant women were divided into three groups: group 1 (healthy control, n = 31),
      group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of
      diazepam plasma concentrations were collected and measured (after the
      administration of the same dose of diazepam), before, during and after delivery.
      The first set of blood samples was taken from the mother (maternal venous
      plasma). The second set of samples was taken from the fetus (fetal umbilical
      venous and arterial plasma). In order to assess the effect of diabetes and
      hypertension on diazepam placental-permeation, the ratios of fetal to maternal
      blood concentrations were determined. Differences were considered statistically
      significant if p <= 0.05. RESULTS: The diabetes and hypertension groups have 2
      fold increase in the fetal umbilical-venous concentrations, compared to the
      maternal venous concentrations. Feto: maternal plasma-concentrations ratios were
      higher in diabetes (2.01 +/- 1.10) and hypertension (2.26 +/- 1.23) groups
      compared with control (1.30 +/- 0.48) while, there was no difference in ratios
      between the diabetes and hypertension groups. Umbilical-cord arterial: venous
      ratios (within each group) were similar among all groups (control: 0.97 +/- 0.32;
      hypertension: 1.08 +/- 0.60 and diabetes: 1.02 +/- 0.77). CONCLUSIONS: On line
      with our previous findings which demonstrate disturbed transcellular trafficking
      of lipophilic drugs in diabetes, this study shows significant increase in
      diazepam placental-permeation in diabetic and hypertensive pregnant women
      suggesting poor transcellular control of drug permeation and flux, and bigger
      exposure of the fetus to drug-placental transport.

PMID- 24134699
TI  - Ferromagnetism in exfoliated tungsten disulfide nanosheets.
AB  - Two-dimensional-layered transition metal dichalcogenides nanosheets have
      attracted tremendous attention for their promising applications in spintronics
      because the atomic-thick nanosheets can not only enhance the intrinsic properties
      of their bulk counterparts, but also give birth to new promising properties. In
      this paper, ultrathin tungsten disulfide (WS2) nanosheets were gotten by liquid
      exfoliation route from its bulk form using dimethylformamide (DMF). Compared to
      the antiferromagnetism bulk WS2, ultrathin WS2 nanosheets show intrinsic room
      temperature ferromagnetism (FM) with the maximized saturation magnetization of
      0.004 emu/g at 10 K, where the appearance of FM in the nanosheets is partly due
      to the presence of zigzag edges in the magnetic ground state at the grain
      boundaries. 

PMID- 24134700
TI  - Producing homogeneous cryogel phantoms for medical imaging: a finite-element
      approach.
AB  - Tissue-mimicking phantoms with well-defined properties can help in identifying
      the potential weaknesses in medical imaging systems. Among the imaging systems,
      magnetic resonance elastography is a new noninvasive technique used to quantify
      the shear modulus of biological tissues, and therefore has shown promise in
      studying liver and brain pathologies. Polyvinyl alcohol (PVA) cryogel prepared by
      the freeze-thaw technique is a potential candidate for mimicking the mechanical
      properties of soft tissues and has been extensively used as a phantom material.
      However, large PVA cryogels suffer from variations in properties, partly due to
      the low thermal conductivity of PVA solution. The loss of homogeneity in cryogel
      phantoms is also attributed to inhomogeneous thawing rates during the freeze-thaw
      cycle. We have used a modified freeze-thaw process that imposes multiple
      isotherms so as to enhance the homogeneity of the produced cryogels. In addition,
      we have developed a finite-element modeling tool (a virtual controller) to
      optimize the temperature profile during the freeze-thaw cycle. Our experimental
      validations demonstrated the potential of the virtual controller in predicting
      the optimal temperature profile for the freeze-thaw process (phantom diameters:
      60 and 100 mm). A robust simulation framework can fill the gap in the scientific
      literature with regard to phantom design for medical imaging and will help to
      reduce phantom development time and cost.

PMID- 24134698
TI  - Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to
      promote electron transport and optimize mitochondrial ATP synthesis.
AB  - BACKGROUND AND PURPOSE: Cardiolipin plays an important role in mitochondrial
      respiration and cardiolipin peroxidation is associated with age-related diseases.
      Hydrophobic interactions between cytochrome c and cardiolipin converts cytochrome
      c from an electron carrier to a peroxidase. In addition to cardiolipin
      peroxidation, this impedes electron flux and inhibits mitochondrial ATP
      synthesis. SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2 ) selectively binds to
      cardiolipin and inhibits cytochrome c peroxidase activity. Here, we examined
      whether SS-31 also protected the electron carrier function of cytochrome c.
      EXPERIMENTAL APPROACH: Interactions of SS-31 with cardiolipin were studied using
      liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin.
      Structural interactions were assessed by fluorescence spectroscopy, turbidity and
      nuclear magnetic resonance. Effects of cardiolipin on electron transfer kinetics
      of cytochrome c were determined by cytochrome c reduction in vitro and oxygen
      consumption using mitoplasts, frozen and fresh mitochondria. KEY RESULTS: SS-31
      interacted only with liposomes and bicelles containing cardiolipin in about 1:1
      ratio. NMR studies demonstrated that the aromatic residues of SS-31 penetrated
      deep into cardiolipin-containing bilayers. SS-31 restored cytochrome c reduction
      and mitochondrial oxygen consumption in the presence of added cardiolipin. In
      fresh mitochondria, SS-31 increased state 3 respiration and efficiency of ATP
      synthesis. CONCLUSIONS AND IMPLICATIONS: SS-31 selectively targeted cardiolipin
      and modulated its interaction with cytochrome c. SS-31 inhibited the cytochrome
      c/cardiolipin complex peroxidase activity while protecting its ability to serve
      as an electron carrier, thus optimizing mitochondrial electron transport and ATP
      synthesis. This novel class of cardiolipin therapeutics has the potential to
      restore mitochondrial bioenergetics for treatment of numerous age-related
      diseases.

PMID- 24134701
TI  - Melatonin administration decreases adipogenesis in the liver of ob/ob mice
      through autophagy modulation.
AB  - Despite efforts to curb the incidence of obesity and its comorbidities, this
      condition remains the fifth leading cause of death worldwide. To identify ways to
      reduce this global effect, we investigated the actions of daily melatonin
      administration on oxidative stress parameters and autophagic processes as a
      possible treatment of obesity in ob/ob mice. The involvement of melatonin in many
      physiological functions, such as the regulation of seasonal body weight
      variation, glucose uptake, or adiposity, and the role of this indoleamine as an
      essential antioxidant, has become the focus of numerous anti-obesity studies.
      Here, we examined the oxidative status in the livers of obese melatonin-treated
      and untreated mice, observing a decrease in the oxidative stress levels through
      elevated catalase activity. ROS-mediated autophagy was downregulated in the liver
      of melatonin-treated animals and was accompanied by significant accumulation of
      p62. Autophagy is closely associated with adipogenesis; in this study, we report
      that melatonin-treated obese mice also showed reduced adiposity, as demonstrated
      by diminished body weight and reduced peroxisome proliferator-activated receptor
      gamma expression. Based on these factors, it is reasonable to assume that
      oxidative stress and autophagy play important roles in obesity, and therefore,
      melatonin could be an interesting target molecule for the development of a
      potential therapeutic agent to curb body weight. 

PMID- 24134702
TI  - MicroRNA-7 inhibition rescues age-associated loss of epidermal growth factor
      receptor and hyaluronan-dependent differentiation in fibroblasts.
AB  - Age-related defects in fibroblast differentiation were previously shown to be
      associated with impaired hyaluronan synthase 2 (HAS2) and epidermal growth factor
      receptor (EGFR) function, with both required for normal fibroblast functionality.
      In fibroblasts, transforming growth factor-beta 1 (TGF-beta1)-dependent
      phenotypic activation uses two distinct but co-operating pathways that involve
      TGF-beta receptor (TGF-betaR)/Smad2 activation and HA-mediated CD44-EGFR co
      localization and signalling through extracellular signal-regulated kinase 1/2
      (ERK1/2). The HA-mediated CD44-EGFR pathway was found to be compromised with in
      vitro aging, through loss of EGFR expression and a reduced movement of CD44
      throughout the cellular membrane. Here, we also investigate the involvement of
      microRNAs (miRNAs) in age-related loss of differentiation, through investigation
      of miRNA-7 (miR-7) regulation of the HA-mediated EGFR-signalling pathway. The
      transcription of miR-7 was found to be upregulated in aged cells. In young cells,
      age-related loss of differentiation could be mimicked through transfection of pre
      miR-7, and in aged cells, could be reversed through transfection of locked
      nucleic acids (LNA) targeting miR-7. Additionally, miR-7 was found to be involved
      in the regulation of CD44 membrane motility, which was downregulated in instances
      of miR-7 upregulation, and partially restorable through either miR-7 inhibition
      or HAS2 overexpression. The altered dynamics of CD44 in the cell membrane
      demonstrated a further action of miR-7 in regulating the HA-dependent CD44/EGFR
      pathway. We explain this novel mechanism of age-associated functional consequence
      due to miR-7 upregulation and demonstrate that it is reversible; highlighting miR
      7 as a potential target for restoring the healing capabilities in chronic wounds
      in the elderly. 

PMID- 24134703
TI  - Functional and population genomic divergence within and between two species of
      killifish adapted to different osmotic niches.
AB  - Adaptation to salinity affects species distributions, promotes speciation, and
      guides many evolutionary patterns in fishes. To uncover the basis of a complex
      trait like osmoregulation, genome-level analyses are sensible. We combine
      population genomic scans with genome expression profiling to discover candidate
      genes and pathways associated with divergence between osmotic environments. We
      compared transcriptome sequence divergence between multiple freshwater and
      saltwater populations of the rainwater killifish, Lucania parva. We also compared
      sequence divergence between L. parva and its sister species, Lucania goodei, a
      freshwater specialist. We found highly differentiated single nucleotide
      polymorphisms (SNPs) between freshwater and saltwater L. parva populations in
      cell junction and ion transport genes, including V-type H(+) ATPase. Between
      species, we found divergence in reproduction and osmotic stress genes. Genes that
      were differentially expressed between species during osmotic acclimation included
      genes involved in ion transport and cell volume regulation. Gene sets that were
      divergent in coding sequence and divergent in expression did not overlap,
      although they did converge in function. Like many studies using genomic scans,
      our approach may miss some loci that contribute to adaptation but have
      complicated patterns of allelic variation. Our study suggests that gene
      expression and coding sequence may evolve independently as populations adapt to a
      complex physiological challenge.

PMID- 24134704
TI  - Association of BK viremia with human leukocyte antigen mismatches and acute
      rejection, but not with type of calcineurin inhibitor.
AB  - INTRODUCTION: BK viremia and polyomavirus-associated nephropathy (PVN) represent
      a significant problem after kidney transplantation. Both are associated with
      intensified immunosuppression, but other risk factors and the impact of a
      screening program on outcome are incompletely understood. METHODS: Here, we
      report on the short- and long-term outcome of a cohort of patients, who were
      transplanted in 2006/2007 and included in a newly introduced systematic 3-monthly
      screening for BK viremia at the University Hospital Zurich. In patients testing
      positive for BK viremia, screening frequency was intensified and
      immunosuppression reduced. Patients with suspected PVN underwent transplant
      biopsy. RESULTS: Among 152 included patients, 49 (32%) tested positive for BK
      viremia, but only 8 developed biopsy-proven PVN. BK viremia had a significant
      impact on estimated glomerular filtration rate and proteinuria in the first 2
      years. Acute rejection episodes and the number of human leukocyte antigen (HLA)
      mismatches were the strongest independent predictors of BK viremia in a multiple
      logistic model. In contrast, no particular immunosuppressive agent or regimen was
      associated with enhanced risk. CONCLUSION: Taken together, systematic BK viremia
      screening led to detection of a high percentage of viremic patients. With
      adjustment of immunosuppression, an excellent outcome was achieved. The
      independent association of HLA mismatches with BK viremia suggests impaired
      polyomavirus immunosurveillance in highly mismatched allografts.

PMID- 24134705
TI  - Novel isoprenoyl nanoassembled prodrug for paclitaxel delivery.
AB  - A new paclitaxel (Ptx) prodrug was designed by coupling a single terpene unit
      (MIP) to the hydroxyl group in position 2' of the drug molecule. Using a squalene
      derivative of polyethylene glycol (SQ-PEG) as surface active agent, the resulting
      bioconjugate (PtxMIP) self-assembled in water leading to the formation of stable
      nanoparticles (PtxMIP_SQ-PEG NPs) with an impressively high drug loading (82%).
      In vivo, the anticancer activity of this novel Ptx nanoassembled prodrug was
      compared to the conventional Cremophor-containing formulation (Taxol) on a murine
      model of breast cancer lung metastasis induced by intravenous injection of 4T1
      tumor cells, genetically modified to stably express firefly luciferase. Cell
      growth was assessed noninvasively by bioluminescence imaging (BLI) which enabled
      monitoring tumor metastatic burden in the same animals. PtxMIP_SQ-PEG
      nanoparticles slowed metastatic spread and were better tolerated than the
      Cremophor-containing formulation (i.e., free drug), thus demonstrating the
      potential of terpene-based nanoassembled prodrugs in the improvement of the
      therapeutic index of Ptx in balb/c mice. 

PMID- 24134706
TI  - Cross-correlation evaluated muscle co-ordination for speech production.
AB  - Abstract In this investigation the jaw-mouth-lip (JML) co-ordination is
      quantified using cross-correlation (CC) between facial electromyography (EMG)
      while speaking words 'zero to nine'. The facial EMG data of four prominent facial
      muscles, namely Zygomaticus Major (ZM) from the mouth region, Levator Labii
      Superioris (LLS), Orbicularis Oris Inferioris (OOI) from the lip region and
      Anterior Belly of Diagastric (ABD) from the jaw region are collected and
      analysed. A total of six muscle pairs, (1) ABD-ZM, (2) ZM-LLS, (3) OOI-ZM, (4)
      ABD-LLS, (5) ABD-OOI and (6) LLS-OOI, are formed based on their position. Based
      on correlation study, all these muscle pairs show a significantly different co
      ordination level (p<0.05). The CC of the ABD-LLS muscle pair is observed with
      maximum co-ordination level among all spoken words (Tukey's post-hoc,
      alpha=0.05). These investigations based on CC in JML co-ordination could be used
      in designing various biomedical engineering tools such as speech prosthesis,
      facial lie detectors, etc.

PMID- 24134707
TI  - Advanced drug delivery nanosystems (aDDnSs): a mini-review.
AB  - Significant progress has been made in nanoscale drugs and delivery systems
      employing diverse chemical formulations to facilitate the rate of drug delivery
      and to improve its pharmacokinetics. Biocompatible nanomaterials have been used
      as biological markers, contrast agents for imaging, healthcare products,
      pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and
      treatment of various types of diseases. The classification of drug delivery
      nanosystems (DDnSs) is a crucial issue and fundamental efforts on this subject
      are missing from the literature. This article deals with the classification of
      DDnSs with a modulatory controlled release profile (MCR) denoted as modulatory
      controlled release nanosystems (MCRnSs). Conventional (c) and advanced (a) DDnSs
      are denoted by the acronyms cDDnSs and aDDnSs, and can be composed of a single or
      more than one biomaterials, respectively. The classification was based on their
      characteristics such as: surface functionality (f), the nature of biomaterials
      used and the kind of interactions between biomaterials. The aDDnSs can be
      classified as hybridic (Hy-) or chimeric (Chi-) based on the nature - same or
      different respectively - of biomaterials and inorganic materials used. The nature
      of the elements used for producing advanced biomaterials is of great importance
      and medicinal chemistry contributes effectively to the production of aDDnSs.

PMID- 24134708
TI  - Illuminating the second conduction band and spin-orbit energy in single wurtzite
      InP nanowires.
AB  - We use polarized photoluminescence excitation spectroscopy to observe the energy
      and symmetry of the predicted second conduction band in 130 nm diameter wurtzite
      InP nanowires. We find direct spectroscopic signatures for optical transitions
      among the A, B, and C hole bands and both the first and the second conduction
      bands. We determine that the splitting between the first and second conduction
      bands is 228 +/- 7 meV in excellent agreement with theory. From these energies we
      show that the spin-orbit energy changes substantially between zinc blende and
      wurtzite InP. We discuss the two quite different solutions within the quasi-cubic
      approximation and the implications for these measurements. Finally, the
      observation of well-defined optical transitions between the B- and C-hole bands
      and the second conduction band suggests that either the theoretical description
      of the second conduction band as possessing Gamma8 symmetry is incomplete, or
      other interactions are enabling these forbidden transitions. 

PMID- 24134709
TI  - Balance--a pragmatic randomized controlled trial of an online intensive self-help
      alcohol intervention.
AB  - AIMS: To compare a brief versus a brief plus intensive self-help version of
      'Balance', a fully automated online alcohol intervention, on self-reported
      alcohol consumption. DESIGN: A pragmatic randomized controlled trial.
      Participants in both conditions received an online single session screening
      procedure including personalized normative feedback. The control group also
      received an online booklet about the effects of alcohol. The treatment group
      received the online multi-session follow-up program, Balance. SETTING: Online
      study in Norway. PARTICIPANTS: At-risk drinkers were recruited by internet
      advertisements and assigned randomly to one of the two conditions (n = 244).
      MEASUREMENTS: The primary outcome was self-reported alcohol consumption the
      previous week measured 6 months after screening. FINDINGS: Regression analysis,
      using baseline carried forward imputation (intent-to-treat), with baseline
      variables as covariates, showed that intervention significantly affected alcohol
      consumption at 6 months (B = 2.96; 95% confidence interval = 0.02-5.90; P =
      0.049). Participants in the intensive self-help group drank an average of three
      fewer standard alcohol units compared with participants in the brief self-help
      group. CONCLUSIONS: The online Balance intervention, added to a brief online
      screening intervention, may aid reduction in alcohol consumption compared with
      the screening intervention and an educational booklet.

PMID- 24134710
TI  - Cyclic di-GMP inhibits Vibrio cholerae motility by repressing induction of
      transcription and inducing extracellular polysaccharide production.
AB  - Cyclic di-GMP (c-di-GMP) controls the transition between sessility and motility
      in many bacterial species. This regulation is achieved by a variety of mechanisms
      including alteration of transcription initiation and inhibition of flagellar
      function. How c-di-GMP inhibits the motility of Vibrio cholerae has not been
      determined. FlrA, a homologue of the c-di-GMP binding Pseudomonas aeruginosa
      motility regulator FleQ, is the master regulator of the V. cholerae flagellar
      biosynthesis regulon. Here we show that binding of c-di-GMP to FlrA abrogates
      binding of FlrA to the promoter of the flrBC operon, deactivating expression of
      the flagellar biosynthesis regulon. FlrA does not regulate expression of
      extracellular Vibrio polysaccharide (VPS) synthesis genes. Mutation of the FlrA
      amino acids R135 and R176 to histidine abrogates binding of c-di-GMP to FlrA,
      rendering FlrA active in the presence of high levels of c-di-GMP. Surprisingly, c
      di-GMP still inhibited the motility of V. cholerae only expressing the c-di-GMP
      blind FlrA(R176H) mutant. We determined that this flagellar transcription
      independent inhibition is due to activation of VPS production by c-di-GMP.
      Therefore, c-di-GMP prevents motility of V. cholerae by two distinct but
      functionally redundant mechanisms. 

PMID- 24134714
TI  - Areca use among adolescents in Yap and Pohnpei, the Federated States of
      Micronesia.
AB  - OBJECTIVE: Areca (Betel Nut) is the fourth most commonly used psychoactive drug
      throughout the world and is legal in U.S. It is carcinogenic. Within a health
      program in the Federated States of Micronesia we surveyed use among adolescents.
      METHODS: One hundred 7th and 8th graders in Yap and Pohnpei were surveyed and
      clinical oral examinations conducted. The questionnaire included items on Areca:
      age first used Areca, whether peers or family members used Areca, frequency of
      use, whether tobacco was used, and source of Areca. Questions also assessed
      anxiety and depression. Two scales assessed getting along with other kids and
      adaptation to school. RESULTS: 61.5-71.4% of adolescents had ever used Areca and
      54.7-68.6% used it at least once in the last month. CONCLUSION: Most adolescents
      surveyed in Yap and Pohnpei used Areca, which may place these youth at increased
      risk for cancer and health disparities.

PMID- 24134715
TI  - Low-temperature precipitation synthesis of flower-like ZnO with lignin amine and
      its optical properties.
AB  - A facile precipitation method has been developed to synthesize ZnO with [bis(2
      aminoethyl)amino]methyl lignin (lignin amine) that is chemically modified from
      low-cost pulp industrial lignin. The obtained ZnO crystallites have been
      characterized to exhibit a hexagonal wurtzite structure, and their sizes have
      been determined at ca. 24 nm (mean value). These ZnO nanocrystallites are of high
      purity and well crystallized. Our present synthetic approach apparently exempts
      the commonly used calcining purification procedure. It is found that the
      morphology of ZnO and its specific surface area are capable of being tuned by
      varying the added lignin amine amount. Using the optimal 10 mL lignin amine, the
      synthesized ZnO exhibits flower-like morphology with proper specific surface
      area. Additionally, photoluminescence property of the obtainable ZnO displays two
      emissive bands at 383 nm (sharp) and in the range of 480 to 600 nm (broad) at
      room temperature. Their intensities were revealed to depend on the added lignin
      amine amount as well as on the molar ratio of Zn2+/OH-. The present investigation
      demonstrates that our method is simple, eco-friendly, and cost-effective for the
      synthesis of small-size ZnO materials. 

PMID- 24134717
TI  - Trends in antenatal care attendance and health facility delivery following
      community and health facility systems strengthening interventions in Northern
      Uganda.
AB  - BACKGROUND: Maternal morbidity and mortality remains high in Uganda; largely due
      to inadequate antenatal care (ANC), low skilled deliveries and poor quality of
      other maternal health services. In order to address both the demand and quality
      of ANC and skilled deliveries, we introduced community mobilization and health
      facility capacity strengthening interventions. METHODS: Interventions were
      introduced between January 2010 and September 2011. These included: training
      health workers, provision of medical supplies, community mobilization using
      village health teams, music dance and drama groups and male partner access clubs.
      These activities were implemented at Kitgum Matidi health center III and its
      catchment area. Routinely collected health facility data on selected outcomes in
      the year preceding the interventions and after 21 months of implementation of the
      interventions was reviewed. Trend analysis was performed using excel and
      statistical significance testing was performed using EPINFO StatCal option.
      RESULTS: The number of pregnant women attending the first ANC visit significantly
      increased from 114 to 150 in the first and fourth quarter of 2010 (OR 1.72; 95%
      CI 1.39-2.12) and to 202 in the third quarter of 2011(OR 11.41; 95% CI 7.97
      16.34). The number of pregnant women counselled, tested and given results for HIV
      during the first ANC attendance significantly rose from 92 (80.7%) to 146 (97.3%)
      in the first and fourth quarter of 2010 and then to 201 (99.5%) in the third
      quarter of 2011. The number of male partners counseled, tested and given results
      together with their wives at first ANC visit rose from 13 (16.7%) in the fourth
      quarter of 2009 to 130 (89%) in the fourth quarter of 2010 and to 180 (89.6%) in
      the third quarter of 2011. There was a significant rise in the number of pregnant
      women delivering in the health facility with provision of mama-kits (delivery
      kits), from 74 (55.2%) to 149 (99.3%) in the second and fourth quarter of 2010.
      CONCLUSIONS: Combined community and facility systems strengthening interventions
      led to increased first ANC visits by women and their partners, and health
      facility deliveries. Interventions aimed at increasing uptake of maternal health
      services should address both the demand and availability of quality services.

PMID- 24134716
TI  - Multiple sclerosis treatment and infectious issues: update 2013.
AB  - Immunomodulation and immunosuppression are generally linked to an increased risk
      of infection. In the growing field of new and potent drugs for multiple sclerosis
      (MS), we review the current data concerning infections and prevention of
      infectious diseases. This is of importance for recently licensed and future MS
      treatment options, but also for long-term established therapies for MS. Some of
      the disease-modifying therapies (DMT) go along with threats of specific severe
      infections or complications, which require a more intensive long-term monitoring
      and multi-disciplinary surveillance. We update the existing warning notices and
      infectious issues which have to be considered using drugs for multiple sclerosis.

PMID- 24134718
TI  - Insertional mutagenesis and cloning of the gene required for the biosynthesis of
      the non-host-specific toxin in Cochliobolus lunatus that causes maize leaf spot.
AB  - The maize pathotype Cochliobolus lunatus causes Curvularia leaf spot by producing
      a non-host-specific toxin known as methyl 5-(hydroxymethyl) furan-2-carboxylate
      (M5HF2C). However, related research that explores the genes that control the
      production of this toxin is rare. In the current work, Agrobacterium tumefaciens
      mediated transformation (ATMT) was employed to tag the gene required for the
      biosynthesis of the toxin. Of the 3,000 ATMT transformants recovered, 4 showed a
      significant decline in pathogenicity on maize leaves; 1 transformant, T806,
      produced no detectable M5HF2C. Genomic DNA that flanks the integrated plasmid was
      recovered from one of the mutants. A cosmid clone of the wild-type strain was
      isolated using the recovered DNA as a probe. The results of the structural and
      functional analyses of the region corresponding to the tagged site were then used
      as a basis to successfully clone one gene, called Clt-1. Bioinformatics analysis
      showed that the gene coded a BTB domain-containing protein that comprises 745
      amino acids. Southern analysis revealed that the gene was localized in the genome
      as a single copy. The essential roles of Clt-1 in both toxin production and
      pathogenicity were confirmed by gene disruption experiments. In summary, the
      novel gene Clt-1 is closely associated with toxin production and pathogen
      virulence in leaves of susceptible varieties.

PMID- 24134719
TI  - Comparative pathogenicity, biocontrol efficacy, and multilocus sequence typing of
      Verticillium nonalfalfae from the invasive Ailanthus altissima and other hosts.
AB  - Verticillium wilt, caused by Verticillium nonalfalfae, is currently killing tens
      of thousands of highly invasive Ailanthus altissima trees within the forests in
      Pennsylvania, Ohio, and Virginia and is being considered as a biological control
      agent of Ailanthus. However, little is known about the pathogenicity and
      virulence of V. nonalfalfae isolates from other hosts on Ailanthus, or the
      genetic diversity among V. nonalfalfae from confirmed Ailanthus wilt epicenters
      and from locations and hosts not associated with Ailanthus wilt. Here, we
      compared the pathogenicity and virulence of several V. nonalfalfae and V.
      alfalfae isolates, evaluated the efficacy of the virulent V. nonalfalfae isolate
      VnAa140 as a biocontrol agent of Ailanthus in Pennsylvania, and performed
      multilocus sequence typing of V. nonalfalfae and V. alfalfae. Inoculations of
      seven V. nonalfalfae and V. alfalfae isolates from six plant hosts on healthy
      Ailanthus seedlings revealed that V. nonalfalfae isolates from hosts other than
      Ailanthus were not pathogenic on Ailanthus. In the field, 100 canopy Ailanthus
      trees were inoculated across 12 stands with VnAa140 from 2006 to 2009. By 2011,
      natural spread of the fungus had resulted in the mortality of >14,000 additional
      canopy Ailanthus trees, 10,000 to 15,000 Ailanthus sprouts, and nearly complete
      eradication of Ailanthus from several smaller inoculated stands, with the
      exception of a few scattered vegetative sprouts that persisted in the understory
      for several years before succumbing. All V. nonalfalfae isolates associated with
      the lethal wilt of Ailanthus, along with 18 additional isolates from 10 hosts,
      shared the same multilocus sequence type (MLST), MLST 1, whereas three V.
      nonalfalfae isolates from kiwifruit shared a second sequence type, MLST 2. All V.
      alfalfae isolates included in the study shared the same MLST and included the
      first example of V. alfalfae infecting a non-lucerne host. Our results indicate
      that V. nonalfalfae is host adapted and highly efficacious against Ailanthus and,
      thus, is a strong candidate for use as a biocontrol agent.

PMID- 24134720
TI  - Detection of citrus huanglongbing-associated 'Candidatus Liberibacter asiaticus'
      in citrus and Diaphorina citri in Pakistan, seasonal variability, and
      implications for disease management.
AB  - We report the detection of the huanglongbing (HLB)-associated bacterium
      'Candidatus Liberibacter asiaticus' from both plants and insects in Pakistan and
      the seasonal variability in the numbers of 'Ca. L. asiaticus'-positive psyllid
      vector, Diaphorina citri. Our studies showed that 'Ca. L. asiaticus' was
      detectable from trees in areas with maximum temperatures reaching nearly 50
      degrees C (average maximum of 42 degrees C). However, the bacterium was present
      at very low levels in psyllids both in summer (June to August) and autumn
      (September to November) in contrast to reports from Florida, where the bacterium
      was detectable at very high levels during October to November. We hypothesize
      that hot summer temperatures in Pakistan may interfere with acquisition and
      replication of 'Ca. L. asiaticus' in psyllids and may lead to dead or non
      transmissible 'Ca. L. asiaticus' in plants. Psyllid counts were very low in both
      summer and winter, showed a population peak ('Ca. L. asiaticus'-positive vectors)
      in spring, and showed a larger peak ('Ca. L. asiaticus'-free psyllids) in autumn.
      Natural thermotherapy during hot summers and a low vector population during
      environmental extremes may have played a major role in long-term survival of the
      citrus industry in Pakistan. These results may be useful in developing management
      strategies for U.S. citrus industries in Texas and California.

PMID- 24134721
TI  - A method to identify differential expression profiles of time-course gene data
      with Fourier transformation.
AB  - BACKGROUND: Time course gene expression experiments are an increasingly popular
      method for exploring biological processes. Temporal gene expression profiles
      provide an important characterization of gene function, as biological systems are
      both developmental and dynamic. With such data it is possible to study gene
      expression changes over time and thereby to detect differential genes. Much of
      the early work on analyzing time series expression data relied on methods
      developed originally for static data and thus there is a need for improved
      methodology. Since time series expression is a temporal process, its unique
      features such as autocorrelation between successive points should be incorporated
      into the analysis. RESULTS: This work aims to identify genes that show different
      gene expression profiles across time. We propose a statistical procedure to
      discover gene groups with similar profiles using a nonparametric representation
      that accounts for the autocorrelation in the data. In particular, we first
      represent each profile in terms of a Fourier basis, and then we screen out genes
      that are not differentially expressed based on the Fourier coefficients. Finally,
      we cluster the remaining gene profiles using a model-based approach in the
      Fourier domain. We evaluate the screening results in terms of sensitivity,
      specificity, FDR and FNR, compare with the Gaussian process regression screening
      in a simulation study and illustrate the results by application to yeast cell
      cycle microarray expression data with alpha-factor synchronization.The key
      elements of the proposed methodology: (i) representation of gene profiles in the
      Fourier domain; (ii) automatic screening of genes based on the Fourier
      coefficients and taking into account autocorrelation in the data, while
      controlling the false discovery rate (FDR); (iii) model-based clustering of the
      remaining gene profiles. CONCLUSIONS: Using this method, we identified a set of
      cell-cycle-regulated time-course yeast genes. The proposed method is general and
      can be potentially used to identify genes which have the same patterns or
      biological processes, and help facing the present and forthcoming challenges of
      data analysis in functional genomics.

PMID- 24134723
TI  - Study of the anomalous sorption behavior of CO2 into poly(methyl methacrylate)
      films in the vicinity of the critical pressure and temperature using a quartz
      crystal microbalance (QCM).
AB  - The anomalous solubility maximum of CO2 in polymer thin films in the vicinity of
      the critical temperature and pressure has not yet been clearly understood when
      the quartz crystal microbalance (QCM) technique has been used to determine the
      micromass change. In this study, the adsorption of CO2 on the surface of bare
      polished and unpolished crystals at different pressures and temperatures was
      investigated using the QCM technique to illustrate why a plot of the true
      frequency shift as a function of temperature and pressure can intuitively exhibit
      the adsorption behavior of CO2 on bare crystals. The sorption of CO2 into a PMMA
      film at different temperatures, pressures, and PMMA film thicknesses was also
      investigated. An accurate solubility for CO2 in the PMMA film could be obtained
      by an improved data correction method from the linear relation between the true
      frequency shift and the polymer film mass, and the anomalous solubility maximum
      could be corrected by this method. The mechanism of nonabsorbed CO2 transitorily
      staying in the interspace between the PMMA film and the crystal surface can be
      explained by the morphology change of the PMMA film. The assumption of "passerby
      CO2" was satisfactorily confirmed to explain the anomalous sorption behavior of
      CO2 into PMMA films in the vicinity of the CO2 critical temperature and pressure,
      and this assumption could be valid for other CO2-polymer thin film systems. 

PMID- 24134722
TI  - Access to a Cu(II)-O-Cu(II) motif: spectroscopic properties, solution structure,
      and reactivity.
AB  - We report a complex with a rare Cu(II)-O-Cu(II) structural motif that is stable
      at room temperature, which allows its in-depth characterization by a variety of
      spectroscopic methods. Interest in such compounds is fueled by the recent
      discovery that a Cu(II)-O-Cu(II) species on the surface of Cu-ZSM-5 is capable of
      oxidizing methane to methanol, and this in turn ties into mechanistic discussions
      on the methane oxidation at the dicopper site within the particulate methane
      monooxygenase. For the synthesis of our Cu2O complex we have developed a novel,
      neutral ligand system, FurNeu, exhibiting two N-(N',N'-dimethylaminoethyl)(2
      pyridylmethyl)amino binding pockets connected by a dibenzofuran spacer. The
      reaction of FurNeu with CuCl yielded [FurNeu](Cu2(MU-Cl))(CuCl2), 1,
      demonstrating the geometric potential of the ligand to stabilize Cu-X-Cu
      moieties. A Cu(I) precursor with weakly coordinating anions was chosen in the
      next step, namely [Cu(NCCH3)4]OTf, which led to the formation of
      [FurNeu](Cu(NCCH3))2(OTf)2, 3. Treatment of 3 with O2 or PhIO led to identical
      green solutions, whose UV-vis spectra were markedly different from the one
      displayed by [FurNeu](Cu)2(OTf)4, 4, prepared independently from FurNeu and
      Cu(OTf)2. Further investigations including PhIO consumption experiments, NMR and
      UV-vis spectroscopy, HR-ESI mass spectrometry, and protonation studies led to the
      identification of the green product as [FurNeu](Cu2(MU-O))(OTf)2, 5. DOSY NMR
      spectroscopy confirmed its monomeric character. Over longer periods of time 5
      decomposes to give [Cu(picoloyl)2], formed through an oxidative N-dealkylation
      reaction followed by further oxidation of the ligand. Due to its slow
      decomposition reaction, all attempts to crystallize 5 failed. However, its
      structure in solution could be determined by EXAFS analysis in combination with
      DFT calculations, which revealed a Cu-O-Cu angle that amounts to 105.17 degrees .
      Moreover, TDDFT calculations helped to rationalize the UV-vis absorptions of 5.
      The reactivity of complex 5 with 2,4-di-tert-butylphenol, DTBP, was also
      investigated; the initially formed biphenol product, TBBP, was found to further
      react in the presence of excessive O2 to yield 2,4,7,9-tetra-tert
      butyloxepino[2,3-b]benzofuran, TBOBF, via an intermediate diphenoquinone. It
      turned out that 5, or its precursor 3, can even be employed as a catalyst for the
      oxidation of DTBP to TBBP or for the oxidation of TBBP to TBOBF. 

PMID- 24134724
TI  - Evaluation of clinical and laboratory correlates of sickle leg ulcers.
AB  - The exact mechanism for the occurrence of sickle leg ulcers (SLUs) has not been
      fully explained, although, popular opinion supports a multifactorial etio
      pathogenetic process. Leg ulceration in sickle cell is a chronic and debilitating
      condition which is difficult to treat and may worsen the psychosocial impact of
      this illness. This study aims to evaluate the laboratory and clinical correlates
      of SLUs. One hundred sixty-seven patients who had been diagnosed with sickle cell
      anemia (homozygous S) had their steady-state hemoglobin concentration (Hb),
      hematocrit, white cell count, platelet count, serum bilirubin, and aspartate
      transaminase (AST) as well as frequency of crisis per annum evaluated with
      respect to their relationship to the occurrence of leg ulcers. They were aged 6
      53 years (mean age 24.3 years), and prevalence of leg ulcer was found to be 2.75
      per 1000 (2.54 per 1000 in females and 2.83 per 1000 in males). The independent
      sample t-test showed a significant difference in the serum AST levels in those
      with SLU (p = 0.029), though a positive correlation did not exist. Other
      predictors of disease severity found to have positive relationship with each
      other were the AST and total serum bilirubin 0.207 (p = 0.012); Hb and age 0.130
      (p = 0.035); Hb and white cell count -0.159 (p = 0.010), white cell count and age
      -0.113 (p = 0.018). SLUs do not occur in patients with severe disease in sickle
      cell. The clinical and laboratory indicators of severe sickle cell disease do not
      correlate positively with the occurrence of SLU. Serum AST may have a
      relationship with leg ulceration in these patients. Environmental factors most
      likely play a major part in the etiopathogenesis of leg ulcer and this may
      require further studies in different sociocultural settings.

PMID- 24134725
TI  - Effects of thymoquinone on STZ-induced diabetic nephropathy: an
      immunohistochemical study.
AB  - BACKGROUND: Thymoquinone (TQ) is the most abundant and active ingredient of
      Nigella sativa (NS) seeds. Its hepatic, renal, and cardiac protective effects
      have been demonstrated in animal models. Streptozotocin (STZ) is an antibiotic
      that is widely used experimentally as an agent capable of inducing insulin
      dependent diabetes mellitus (IDDM), also known as type I diabetes mellitus
      (T1DM). OBJECTIVES: This study was carried out in an attempt to highlight the
      possible beneficial effects of TQ in STZ-induced diabetes in rats and to
      determine the predictive value of mesenchymal and epithelial markers in the
      response of diabetic nephropathy to TQ. MATERIALS AND METHODS: Sixty adult male
      albino rats were divided in 3 groups: control, diabetic untreated, and diabetic
      treated with TQ. RESULTS: Diabetic rats exhibited morphological changes in both
      renal glomeruli and tubules with immunohistochemical expression of the
      mesenchymal markers Fsp1, desmin, and MMP-17 and disappearance of the epithelial
      marker ZO-1 largely in the glomeruli of diabetic kidneys. Treatment with TQ
      significantly attenuated renal morphological and immunohistochemical changes in
      STZ-induced diabetic rats. CONCLUSIONS: Thymoquinone has protective effects on
      experimental diabetic nephropathy. Both mesenchymal and epithelial markers serve
      as excellent predictors of early kidney damage and indicators of TQ
      responsiveness in STZ-induced diabetic nephropathy.

PMID- 24134726
TI  - Abstracts of the 18th Congress of the Asian Pacific Society of Respirology.
      November 11-14, 2013. Yokohama, Japan.

PMID- 24134727
TI  - Vanishing-recurrent benign liver lesions.

PMID- 24134728
TI  - Persistent parvovirus B19 infection resulting in red cell aplasia after
      allogeneic hematopoietic stem cell transplantation.
AB  - Persistent parvovirus B19 (PVB) infection has been reported sporadically in
      immunocompromised patients including hematopoietic stem cell and solid organ
      transplant recipients. However, the pathogenesis of persistent infection has yet
      to be fully elucidated. We report here a patient with multiple myeloma developing
      red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic
      stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB
      viremia before transplantation and remained asymptomatic. The route of PVB
      transmission was considered to be direct contact with the patient's family member
      with primary PVB infection 1 month before transplantation. Treatment with
      intravenous immunoglobulin resulted in prompt resolution of anemia. These
      findings suggest that monitoring of PVB DNA is recommended for patients
      undergoing HSCT and having contact with individuals with documented PVB
      infection, even if they are asymptomatic.

PMID- 24134730
TI  - Considerable variation among Iranian dermatologists in the dosing and monitoring
      of methotrexate for treating psoriasis.
AB  - BACKGROUND: Methotrexate (MTX) is a risky medication requiring careful attention
      to dosing and monitoring. Dosing and monitoring practices are not well
      characterized. AIMS: The aim of this study was to assess variation in the dosing
      and monitoring of methotrexate among Iranian dermatologists. METHODS: A
      questionnaire was administered to forty experts in psoriasis concerning the use
      of MTX. RESULTS: Among the 39 responding dermatologists (15 women, 24 men), 54%
      saw fewer than 10 psoriatic patients per week, 23% 10-20 patients, and 23% more
      than 20 patients. About half of the dermatologists treat their patients with an
      initial MTX dose of <7.5 mg/week (range 5-17.5 mg/week), an average dose of <10
      mg/week (range 5-25 mg/week), and a maximum dose of <20 mg/week (range 7.550 -
      mg/week) with 71.8% prescribing the medication orally and 28.2% intramuscularly.
      Subcutaneous injection was preferred by none of the dermatologists as a usual
      route of administration. Nearly 5% of the dermatologists believe that liver
      biopsy should be performed prior to treatment with MTX in all patients, and
      another 5% consider this procedure prior to treatment only in patients with risk
      factors. About 44 and 33% of the dermatologists do the liver biopsy after 1.0-1.5
      g and 3.54 g total cumulative doses, respectively. CONCLUSION: After more than a
      half century, there are still noticeable controversies on the manner of using MTX
      in treating psoriasis among Iranian dermatologists. A national guideline may help
      standardize treatment practices.

PMID- 24134731
TI  - A new route for polar navigation.
AB  - Placement of motility structures at the poles of rod-shaped bacteria is a common
      engineering problem with a variety of potential solutions. While investigating
      the mechanisms for positioning of the single polar flagellum of Pseudomonas
      aeruginosa, Cowles and colleagues discovered a new membrane-bound three-component
      system related to TonB-ExbB-ExbD that they named 'Poc' for polar organelle co
      ordinator, which controls polar localization of both the flagellum and type IV
      pili. The Poc complex itself is not found at the poles, and is required for
      increased expression of pilus genes upon surface association, suggesting a new
      paradigm of localization control. 

PMID- 24134732
TI  - Host-specialist lineages dominate the adaptive radiation of reef coral
      endosymbionts.
AB  - Bursts in species diversification are well documented among animals and plants,
      yet few studies have assessed recent adaptive radiations of eukaryotic microbes.
      Consequently, we examined the radiation of the most ecologically dominant group
      of endosymbiotic dinoflagellates found in reef-building corals, Symbiodinium
      Clade C, using nuclear ribosomal (ITS2), chloroplast (psbA(ncr)), and multilocus
      microsatellite genotyping. Through a hierarchical analysis of high-resolution
      genetic data, we assessed whether ecologically distinct Symbiodinium,
      differentiated by seemingly equivocal rDNA sequence differences, are independent
      species lineages. We also considered the role of host specificity in Symbiodinium
      speciation and the correspondence between endosymbiont diversification and
      Caribbean paleo-history. According to phylogenetic, biological, and ecological
      species concepts, Symbiodinium Clade C comprises many distinct species. Although
      regional factors contributed to population-genetic structuring of these lineages,
      Symbiodinium diversification was mainly driven by host specialization. By
      combining patterns of the endosymbiont's host specificity, water depth
      distribution, and phylogeography with paleo-historical signals of climate change,
      we inferred that present-day species diversity on Atlantic coral reefs stemmed
      mostly from a post-Miocene adaptive radiation. Host-generalist progenitors
      spread, specialized, and diversified during the ensuing epochs of prolonged
      global cooling and change in reef-faunal assemblages. Our evolutionary
      reconstruction thus suggests that Symbiodinium undergoes "boom and bust" phases
      in diversification and extinction during major climate shifts.

PMID- 24134733
TI  - Accuracy of endodontic working length determination using cone beam computed
      tomography.
AB  - AIM: To evaluate the accuracy of endodontic working length (WL) measurements by
      cone beam computed tomography (CBCT). METHODOLOGY: Forty-two extracted human
      teeth were placed into three full jaw models. Preoperatively, CBCT scans of the
      models were performed (voxel size: 0.2 mm). Endodontic access cavities were
      prepared, and the coronal third of 70 root canals were pre-flared. The real WL
      was measured by inserting a K-file into the root canal until the tip was visible
      at the foramen, a silicon stopper was adjusted to the corresponding cusp tip, and
      the length was measured using a micrometer. CBCT WL was simply measured by
      tracing a line between the apical foramen and the corresponding cusp tip. When
      the foramen and cusp tip were not visible in one plane, the measurement was taken
      in two planes. To quantify measurement error, real and CBCT WLs were repeated
      four times by two experienced operators. Paired analysis for each variable was
      performed, and the mean of absolute differences and the corresponding 99%
      confidence intervals were calculated. The t-test was used for comparison.
      RESULTS: The coefficient of repeatability, reproducibility and interoperator
      agreement were <0.5 mm. CBCT measurements were accurate; the mean of absolute
      differences between CBCT and real WL was 0.41 mm (99% CI 0.31-0.52 mm).
      CONCLUSION: Using a simplified method, CBCT images of 0.2 mm voxel size can be
      used to accurately determine endodontic WL.

PMID- 24134734
TI  - Dynamic micelles of mannoside glycolipids are more efficient than polymers for
      inhibiting HIV-1 trans-infection.
AB  - Mannoside glycolipid conjugates are able to inhibit human immunodeficiency virus
      type 1 (HIV-1) trans-infection mediated by human dendritic cells (DCs). The
      conjugates are formed by three building blocks: a linear or branched mannose
      head, a hydrophilic linker, and a 24-carbon lipid chain. We have shown that, even
      as single molecules, these compounds efficiently target mannose-binding lectins,
      such as DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) important for HIV-1
      transmission. With the goal to optimize their inhibitory activity by
      supramolecular structure formation, we have compared saturated and unsaturated
      conjugates, as single molecules, self-assemblies of dynamic micelles, and
      photopolymerized cross-linked polymers. Surface plasmon resonance showed that,
      unexpectedly, polymers of trivalent conjugates did not display a higher binding
      affinity for DC-SIGN than single molecules. Interactions on a chip or in solution
      were independent of calcium; however, binding to DCs was inhibited by a calcium
      chelator. Moreover, HIV-1 trans-infection was mostly inhibited by dynamic
      micelles and not by rigid polymers. The inhibition data revealed a clear
      correlation between the structure and molecular assembly of a conjugate and its
      biological antiviral activity. We present an interaction model between DC-SIGN
      and conjugates-either single molecules, micelles, or polymers-that highlights
      that the most effective interactions by dynamic micelles involve both mannose
      heads and lipid chains. Our data reveal that trivalent glycolipid conjugates
      display the highest microbicide potential for HIV prophylaxis, as dynamic
      micelles conjugates and not as rigid polymers. 

PMID- 24134735
TI  - Moderate and severe periodontitis are independent risk factors associated with
      low cardiorespiratory fitness in sedentary non-smoking men aged between 45 and 65
      years.
AB  - AIM: To investigate the association between periodontal disease severity and
      cardiorespiratory fitness (CRF) in a cross-sectional study of sedentary men.
      MATERIALS & METHODS: Seventy-two healthy men (45-65 years) who did not join any
      sport activity and had a preferentially sitting working position were recruited.
      Periodontal status was recorded and CRF was measured by peak oxygen uptake (VO2
      peak ) during exercise testing on a cycle ergometer. Physical activity was
      assessed by a validated questionnaire and data were transformed to metabolic
      equivalent of task scores. Univariate and multivariate regression analyses were
      performed to investigate associations. RESULTS: Differences between VO2 peak
      levels in subjects with no or mild, moderate or severe periodontitis were
      statistically significant (p = 0.026). Individuals with low VO2 peak values
      showed high BMI scores, high concentrations of high-sensitive C-reactive protein,
      low levels of high-density lipoprotein-cholesterol, and used more glucocorticoids
      compared to individuals with high VO2 peak levels. Multivariate regression
      analysis showed that high age (p = 0.090), high BMI scores (p < 0.001), low
      levels of physical activity (p = 0.031) and moderate (p = 0.087), respectively,
      severe periodontitis (p = 0.033) were significantly associated with low VO2 peak
      levels. CONCLUSIONS: This study demonstrated that moderate and severe
      periodontitis were independently associated with low levels of CRF in sedentary
      men aged between 45 and 65 years.

PMID- 24134737
TI  - Poor school performance is associated with a larger gain in body mass index
      during puberty.
AB  - AIM: Social inequalities in type 2 diabetes and coronary heart disease may be
      established in formative school years. We investigated whether school performance
      is associated with adiposity and increase in body mass index (BMI) between 10 and
      15 years of age. METHODS: A community sample of 2633 school children had height
      and weight measured in school at the ages of 10 and 15. Percentages of body fat
      and waist circumference were measured at the age of 15. Mean grades in several
      school subjects at the age of 15 (ninth school year) were divided into quartiles.
      A linear regression analysis with BMI as the main outcome took into account
      parental education and ethnicity, obtained from registers, and children's living
      habits, collected by questionnaires. RESULTS: In adjusted models, longitudinal
      changes in BMI between the ages of 10 and 15 were larger in the lowest quartiles
      of school grades compared with the highest: for girls, they were beta = 0.45 (p =
      0.007) and for boys they were beta = 0.45 (p = 0.016). Cross-sectional regression
      analyses, with percentage of body fat and waist circumference as outcomes, showed
      similar results. CONCLUSION: Our results suggest that school performance is one
      pathway to social inequalities in obesity in school children.

PMID- 24134736
TI  - GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic
      differentiation of human mesenchymal stem cells.
AB  - The cellular microenvironment plays a crucial role in directing proliferation and
      differentiation of stem cells. Cells interact with their microenvironment via
      integrins that recognize certain peptide sequences of extracellular matrix
      proteins. This receptor-ligand binding has profound impact on cell fate.
      Interactions of human bone marrow mesenchymal stem cells (hMSCs) with the triple
      helical collagen mimetic, GPC(GPP)5-GFOGER-(GPP)5GPC-NH2, and the fibronectin
      adhesion peptide, RGD, were studied in degradable or nondegradable polyethylene
      glycol (PEG) gels formed by Michael-type addition chemistry. Proliferation,
      cytoskeletal morphology, and chondrogenic differentiation of encapsulated hMSCs
      were evaluated. The hMSCs adopted a highly spread morphology within the GFOGER
      modified gels, whereas RGD induced a star-like spreading of the cells. hMSCs
      within GFOGER-modified degradable gels had a high proliferation rate compared
      with cells in peptide-free gels (p=0.017). Gene expression of type II collagen
      was highest in GFOGER-modified degradable gels after 21 days. Peptide
      incorporation increased GAG production in degradable gels after 7 and 21 days and
      GFOGER-modified degradable hydrogels had on average the highest GAG content, a
      finding that was confirmed by Alcian blue staining. In conclusion, the GFOGER
      peptide enhances proliferation in degradable PEG gels and provides a better
      chondrogenic microenvironment compared with the RGD peptide. 

PMID- 24134739
TI  - Music therapy assessment tool for awareness in disorders of consciousness
      (MATADOC): standardisation of the principal subscale to assess awareness in
      patients with disorders of consciousness.
AB  - Establishing valid and reliable measures for use with patients with disorders of
      consciousness (DOC) following profound brain injury is challenging due to a
      number of factors including the complex presentation of such patients and
      assessor variability. The auditory modality has been demonstrated to have greater
      sensitivity for detecting awareness in DOC patients. However, there are no
      measures developed to assess auditory responsiveness specifically. The objective
      of this study was to examine the psychometric properties of the principal
      subscale of a music therapy assessment tool (MATADOC) developed for use with
      adult DOC patients. The subscale assesses behavioural domains essential for
      diagnosis of awareness. Twenty-one adult patients were recruited from a
      specialist rehabilitation unit. In a prospective study with repeated measures,
      internal consistency, inter-rater and test-retest reliability and dimensionality
      were examined. The five-item scale showed satisfactory internal reliability
      (alpha = .76) and a strong first principal component. Corrected item-total
      correlations were all > .45. Inter-rater intra-class correlations (ICCs) ranged
      from 0.65-1.00 and intra-rater ICCs from 0.77-0.90. Rasch analysis confirmed
      these impressions of a reliable, unidimensional and homogenous scale. Diagnostic
      outcomes had 100% agreement with a validated external reference standard. The
      results indicate that the MATADOC principal subscale provides a new behavioural
      measure that can contribute to interdisciplinary assessment of awareness with DOC
      patients. 

PMID- 24134738
TI  - CD4(+) CD25(high) forkhead box protein 3(+) regulatory T lymphocytes suppress
      interferon-gamma and CD107 expression in CD4(+) and CD8(+) T cells from
      tuberculous pleural effusions.
AB  - Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile,
      but an excessive Th1 response may also cause tissue damage that might be
      controlled by regulatory mechanisms. In the current study we investigated the
      role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients
      with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion
      of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-gamma
      and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood
      (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that
      the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+)
      cells were increased in PF compared to PB samples. Mycobacterium tuberculosis
      stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and
      CD4(+) CD25(low/neg) IFN-gamma(+) in PF; meanwhile, CD25(high) mainly expressed
      IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+)
      CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M.
      tuberculosis-induced IFN-gamma and CD4(+) and CD8(+) degranulation responses and
      decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB
      pleurisy Treg cells effectively inhibit not only IFN-gamma expression but also
      the ability of CD4(+) and CD8(+) cells to degranulate in response to M.
      tuberculosis. 

PMID- 24134740
TI  - Charge transport mechanisms and memory effects in amorphous TaNx thin films.
AB  - Amorphous semiconducting materials have unique electrical properties that may be
      beneficial in nanoelectronics, such as low leakage current, charge memory
      effects, and hysteresis functionality. However, electrical characteristics
      between different or neighboring regions in the same amorphous nanostructure may
      differ greatly. In this work, the bulk and surface local charge carrier transport
      properties of a-TaNx amorphous thin films deposited in two different substrates
      are investigated by conductive atomic force microscopy. The nitride films are
      grown either on Au (100) or Si [100] substrates by pulsed laser deposition at 157
      nm in nitrogen environment. For the a-TaNx films deposited on Au, it is found
      that they display a negligible leakage current until a high bias voltage is
      reached. On the contrary, a much lower threshold voltage for the leakage current
      and a lower total resistance is observed for the a-TaNx film deposited on the Si
      substrate. Furthermore, I-V characteristics of the a-TaNx film deposited on Au
      show significant hysteresis effects for both polarities of bias voltage, while
      for the film deposited on Si hysteresis, effects appear only for positive bias
      voltage, suggesting that with the usage of the appropriate substrate, the a-TaNx
      nanodomains may have potential use as charge memory devices. 

PMID- 24134741
TI  - FORUM ISSUE: "Free radicals and physical exercise".

PMID- 24134742
TI  - Three-dimensional nitrogen-doped multiwall carbon nanotube sponges with tunable
      properties.
AB  - A three-dimensional (3D) nitrogen-doped multiwall carbon nanotube (N-MWCNT)
      sponge possessing junctions induced by both nitrogen and sulfur was synthesized
      by chemical vapor deposition (CVD). The formation of "elbow" junctions as well as
      "welded" junctions, which are attributed to the synergistic effect of the
      nitrogen dopant and the sulfur promoter, plays a critically important role in the
      formation of 3D nanotube sponges. To the best of our knowledge, this is the first
      report showing the synthesis of macroscale 3D N-MWCNT sponges. Most importantly,
      the diameter of N-MWCNT can be simply controlled by varying the concentration of
      sulfur, which in turn controls both the sponge's mechanical and its electrical
      properties. It was experimentally shown that, with increasing diameter of N
      MWCNT, the elastic modulus of the sponge increased while the electrical
      conductivity decreased. The mechanical behaviors of the sponges have also been
      quantitatively analyzed by employing strain energy function modeling. 

PMID- 24134743
TI  - Differences in fine-scale spatial genetic structure across the distribution range
      of the distylous forest herb Pulmonaria officinalis (Boraginaceae).
AB  - BACKGROUND: Geographical ranges of plants and their pollinators do not always
      entirely overlap and it has been suggested that the absence of specialized
      pollinators at range margins may induce changes in mating systems. Because a
      species' mating system is known to have a considerable effect on within
      population pollen movement, the extent of fine-scale spatial genetic structure
      (SGS) can be expected to differ between populations located at different parts of
      their geographical range. To test this prediction, we compared the fine-scale SGS
      between two core and two disjunct populations of the distylous forest herb
      Pulmonaria officinalis. Because in disjunct populations of this species the
      heteromorphic self-incompatibility system showed relaxation in the long-styled
      morph, but not in the short-styled morph, we also hypothesized that the extent of
      fine-scale SGS and clustering differed between morphs. RESULTS: Spatial
      autocorrelation analyses showed a significant decrease in genetic relatedness
      with spatial distance for both core and disjunct populations with the weakest SGS
      found in one of the core populations (Sp = 0.0014). No evidence of stronger SGS
      in the long-styled morph was found in the center of the range whereas one
      disjunct population showed a significantly (P = 0.029) higher SGS in the long
      styled morph (SpL = 0.0070) than in the short-styled morph (SpS = 0.0044).
      CONCLUSIONS: Consistent with previous analyses on distylous plant species, we
      found weak, but significant spatial genetic structure. However, the extent of SGS
      varied substantially between populations within regions, suggesting that
      population characteristics other than mating system (e.g. local pollinator
      assemblages, population history) may be as important in determining variation in
      SGS.

PMID- 24134744
TI  - P144, A TGF-beta1 antagonist peptide, synergizes with sildenafil and enhances
      erectile response via amelioration of cavernosal fibrosis in diabetic rats.
AB  - INTRODUCTION: Patients with diabetes exhibit more severe erectile dysfunction
      (ED) and are less responsive to first-line oral phosphodiesterase type 5
      inhibitor (PDE5i). It has been suggested that increased collagen deposition and
      reduced smooth muscle content in the corpus cavernosum are important mechanisms
      for diabetes-associated ED and that transforming growth factor-beta1 (TGF-beta1)
      is a potent fibrotic factor responsible for the structural alterations in the
      corpus cavernosum. AIMS: The aims of this study are to determine whether
      activation of TGF-beta1 and its downstream pathways is responsible for the
      reduced efficacy of the PDE5is in diabetic ED via abnormalities in cavernosal
      structures and to investigate the synergistic effects of the TGF-beta1 antagonist
      P144 and sildenafil on erectile response. METHODS: Six weeks after inducting
      diabetes with streptozotocin in male Sprague-Dawley rats, age-matched control and
      diabetic rats were treated with vehicle, sildenafil, or P144 alone or in
      combination for 4 weeks, respectively. MAIN OUTCOME MEASURES: Intracavernous
      pressure, dynamic infusion cavernosometry, and histological and molecular
      alterations of the corpus cavernosum were analyzed. RESULTS: Diabetic rats
      exhibited a decreased erectile response, severe corporal veno-occlusive
      dysfunction (CVOD), and structural alterations including cavernosal fibrosis and
      decreased smooth muscle content. Expression and activation of TGF-beta1 and its
      downstream Smad and non-Smad pathways increased in diabetic rats. Treatment with
      sildenafil showed modest effect on erectile response and a less suppressive
      effect on CVOD, cavernosal fibrosis, and molecular alterations. Treatment with
      P144 had lower effect on erectile response, even greatly improved the
      histological and molecular alterations and CVOD than sildenafil. The combined
      treatment with P144 and sildenafil effectively restored erectile response, CVOD,
      and histological and molecular alterations. CONCLUSION: An insufficient
      suppressive effect of sildenafil on cavernosal fibrosis, severe CVOD, and TGF
      beta1 pathways was implicated in reduced efficacy of the PDE5i in diabetic ED.
      Treatment with P144 synergized sildenafil and significantly increased erectile
      response by the potential antifibrotic activity.

PMID- 24134745
TI  - Crinophagy in neuroblastoma: a case report and review of the literature.
AB  - Crinophagy is a well-described ultraphysiological phenomenon encountered in a
      variety of cells and tissues. This process reflects a form of autophagy in which
      degradation of excess or nonfunctional cellular constituents occurs, specifically
      of neuroendocrine granules. The diagnostic ultrastructural features are the
      identification of neuroendocrine granules within lysosomes, often encased in or
      accompanied by myelin bodies. An impressive variety of neuroendocrine/secretory
      cells and tumors have demonstrated crinophagy from the neuroendocrine cells of
      the pancreas, small bowel, prostate, and urinary tract. To our knowledge,
      however, crinophagy has not been previously described in neuroblastoma, despite
      the fact that these tumors characteristically produce neuroendocrine granules in
      abundance. This case further supports the idea that crinophagy represents a
      common ultrastructural mechanism for the disposal and degradation of excess
      neuroendocrine granules.

PMID- 24134746
TI  - Chick chorioallantoic membrane model for in ovo evaluation of timolol maleate
      brimonidine tartrate ocular inserts.
AB  - The main aspire of this study was to develop ocular drug delivery system for dual
      drug glaucoma therapy by timolol maleate-brimonidine tartrate and endeavor the
      possibility of biocompatibility studies by in ova studies. Matrix type, both
      hydrophilic and lipophilic polymers, and reservoir-type ocular inserts of timolol
      maleate were prepared using hydrophilic polymers like polyvinyl alcohol, hydroxyl
      propyl methyl cellulose K4M and lipophilic polymers like ethylcellulose and
      eudragit S100 and were optimized. Based on the optimized formulation, triple
      layered ocular inserts (reservoir type) of dual drug were prepared by solvent
      casting technique with an objective of reducing the frequency of administration,
      obtaining controlled release and greater therapeutic efficacy, preservative free
      dosage form for the treatment of glaucoma. FTIR spectral studies revealed no
      pharmaceutical incompatibility and no drug polymer interactions. Maximum drug
      release (99.18 +/- 1.7) was achieved when PVP and HPMC K4M in 1:1 ratio with PEG
      400 (0.3 ml) drug reservoir layer was sandwiched between ethyl cellulose as rate
      control membrane up to 32 h in a controlled fashion. Drug release was by non
      Fickian diffusion mechanism for single drug formulation. But in dual drug insert,
      timolol maleate best fit into zero order and for brimonidine tartrate to Higuchi
      model and diffusion of drugs from this by non-Fickian diffusion mechanism. In ovo
      studies suggested that the optimized formulation was found to be sterile,
      biocompatible and physicochemically stable and support us to claim that the
      developed formulation was biocompatible.

PMID- 24134747
TI  - Formation of a 1,4-diamino-2,3-disila-1,3-butadiene derivative.
AB  - A 1,4-diamino-2,3-disila-1,3-butadiene derivative of composition (Me2
      cAAC)2(Si2Cl2) (Me2-cAAC = :C(CMe2)2(CH2)N-2,6-iPr2C6H3) was synthesized by
      reduction of the Me2-cAAC:SiCl4 adduct with KC8. This compound is stable at 0 
      degrees C for 3 months in an inert atmosphere. Theoretical studies reveal that
      the silicon atoms exhibit pyramidal coordination, where the Cl-Si-Si-Cl dihedral
      angle is twisted by 43.3 degrees  (calcd 45.9 degrees ). The two silicon-carbon
      bonds are intermediates between single and double Si-C bonds due to twisting of
      the C-Si-Si-C dihedral angle (163.6 degrees ). 

PMID- 24134748
TI  - Antibacterial, physicochemical and mechanical properties of endodontic sealers
      containing quaternary ammonium polyethylenimine nanoparticles.
AB  - AIM: To evaluate the antibacterial, physicochemical and mechanical properties of
      two endodontic sealers incorporating quaternary ammonium polyethylenimine (QPEI)
      nanoparticles at concentrations of 1% and 2% (w/w). METHODOLOGY: The sealers
      tested were AH Plus and Pulp Canal Sealer EWT in the commercial unmodified form
      or containing 1% or 2% QPEI. Antibacterial activity was evaluated using a direct
      contact test (DCT) against Enterococcus faecalis ATCC 29212 and two endodontic
      isolates (RW35 and RN44). Sealers freshly mixed or set for 7 days were exposed to
      bacterial suspensions for 10, 30 and 60 min. Setting time, flow test, solubility,
      apparent porosity, dimensional change following setting, wettability, zeta
      potential and compressive strength were assessed according to the International
      Standard Organization 6876:2001 (ISO 6876). RESULTS: DCT results revealed that
      both freshly prepared sealers had antibacterial effects unaffected by QPEI
      incorporation. Both unmodified sealers had lost much of their antibacterial
      effects after 7 days. However, for Pulp Canal Sealer EWT incorporated with 1% and
      2% QPEI nanoparticles, the antibacterial effects against all test E. faecalis
      strains within 30 and 60 min of contact were significantly greater than the
      unmodified formula. Addition of QPEI resulted in no significant increase in the
      antibacterial effects of AH Plus after ageing. As for physicochemical and
      mechanical tests, setting time, wettability and zeta potential were influenced by
      the presence of QPEI nanoparticles. CONCLUSION: Incorporation of QPEI
      nanoparticles can improve the long-term antibacterial activity of Pulp Canal
      Sealer EWT without relevant changes in physicochemical and mechanical properties.

PMID- 24134750
TI  - Role of neuropeptides, neurotrophins, and neurohormones in skin wound healing.
AB  - Due to the close interactions between the skin and peripheral nervous system,
      there is increasing evidence that the cutaneous innervation is an important
      modulator of the normal wound healing process. The communication between sensory
      neurons and skin cells involves a variety of molecules (neuropeptides,
      neurohormones, and neurotrophins) and their specific receptors expressed by both
      neuronal and nonneuronal skin cells. It is well established that
      neurotransmitters and nerve growth factors released in skin have immunoregulatory
      roles and can exert mitogenic actions; they could also influence the functions of
      the different skin cell types during the wound healing process. 

PMID- 24134749
TI  - MC1R genotype as a predictor of early-onset melanoma, compared with self-reported
      and physician-measured traditional risk factors: an Australian case-control
      family study.
AB  - BACKGROUND: Melanocortin-1 receptor (MC1R) gene variants are very common and are
      associated with melanoma risk, but their contribution to melanoma risk prediction
      compared with traditional risk factors is unknown. We aimed to 1) evaluate the
      separate and incremental contribution of MC1R genotype to prediction of early
      onset melanoma, and compare this with the contributions of physician-measured and
      self-reported traditional risk factors, and 2) develop risk prediction models
      that include MC1R, and externally validate these models using an independent
      dataset from a genetically similar melanoma population. METHODS: Using data from
      an Australian population-based, case-control-family study, we included 413 case
      and 263 control participants with sequenced MC1R genotype, clinical skin
      examination and detailed questionnaire. We used unconditional logistic regression
      to estimate predicted probabilities of melanoma. Results were externally
      validated using data from a similar study in England. RESULTS: When added to a
      base multivariate model containing only demographic factors, MC1R genotype
      improved the area under the receiver operating characteristic curve (AUC) by 6%
      (from 0.67 to 0.73; P < 0.001) and improved the quartile classification by a net
      26% of participants. In a more extensive multivariate model, the factors that
      contributed significantly to the AUC were MC1R genotype, number of nevi and
      previous non-melanoma skin cancer; the AUC was 0.78 (95% CI 0.75-0.82) for the
      model with self-reported nevi and 0.83 (95% CI 0.80-0.86) for the model with
      physician-counted nevi. Factors that did not further contribute were sun and
      sunbed exposure and pigmentation characteristics. Adding MC1R to a model
      containing pigmentation characteristics and other self-reported risk factors
      increased the AUC by 2.1% (P = 0.01) and improved the quartile classification by
      a net 10% (95% CI 1-18%, P = 0.03). CONCLUSIONS: Although MC1R genotype is
      strongly associated with skin and hair phenotype, it was a better predictor of
      early-onset melanoma than was pigmentation characteristics. Physician-measured
      nevi and previous non-melanoma skin cancer were also strong predictors. There
      might be modest benefit to measuring MC1R genotype for risk prediction even if
      information about traditional self-reported or clinically measured pigmentation
      characteristics and nevi is already available.

PMID- 24134751
TI  - A review series begins: how much do we know about intractable disease?

PMID- 24134752
TI  - Costal BCG osteomyelitis developing 1 year after BCG vaccination.
AB  - Reported here is the case of a 15-month-old boy with costal osteomyelitis due to
      the bacillus Calmette-Guerin (BCG) vaccine against tuberculosis. Mild
      complications of this vaccine, such as localized abscess and regional
      lymphadenitis, are occasionally recognized, but its association with
      osteomyelitis is extremely rare. 

PMID- 24134753
TI  - Severe posterior reversible encephalopathy syndrome resolved with craniectomy.
AB  - Posterior reversible encephalopathy syndrome (PRES) has been thought to be a
      benign disease, but recently severe cases have been reported with increasing
      recognition. A 3-year-old girl with congenital nephrotic syndrome had rapidly
      progressed to coma. Computed tomography (CT) of the head showed striking swelling
      of the brainstem and transtentorial herniation. Emergency decompressive
      craniectomy was performed. Consecutively, blood pressure was optimally
      controlled. The patient gradually recovered to the previous state before onset of
      PRES. Rapid improvement of clinical symptoms and rapid resolution of abnormal
      findings on serial CT led to diagnosis of PRES. In severe PRES with unstable
      vital signs, surgical intervention should be considered as well as appropriate
      blood pressure management. 

PMID- 24134754
TI  - Childhood-onset hereditary pancreatitis with mutations in the CT gene and SPINK1
      gene.
AB  - Hereditary pancreatitis (HP) is an autosomal-dominant gene disorder. The affected
      genes have been identified as the cationic trypsinogen (CT) gene and the serine
      protease inhibitor Kazal type 1 (SPINK1) gene. These gene abnormalities alone,
      however, do not necessarily regulate the onset or severity of pancreatitis,
      suggesting the involvement of other gene abnormalities and environmental factors.
      Reported herein is the case of a 9-year-old boy with early-onset HP due to
      mutations in the CT and SPINK1 genes. The patient had a p.R122H heterozygous
      mutation in the CT gene and a p.N34S heterozygous mutation in the SPINK1 gene.
      The father had heterozygous mutation of the SPINK1 gene, and the mother had
      heterozygous mutation of the CT gene, although neither had a prior history of
      pancreatitis. In this patient, early onset of HP was attributed to the presence
      of gene abnormalities in the CT and SPINK1 genes. 

PMID- 24134755
TI  - Intussusception secondary to anaphylactic reaction to salmon roe (ikura).
AB  - Anaphylactic food reaction often involves gastrointestinal symptoms, such as
      vomiting and abdominal pain, but to date, there have been no publications
      documenting the association between food hypersensitivity and intussusception.
      Herein is reported the case of a 2-year-old boy with intussusception accompanied
      by anaphylactic food reaction. The patient without known allergies complained of
      severe abdominal pain following ingestion of salmon roe for the first time.
      Dyspnea, wheezing and generalized urticaria also developed. Subsequently, he had
      stools containing jelly-like blood with mucus. At hospital arrival, physical
      examination identified an abdominal mass in the right lower quadrant; imaging
      confirmed the diagnosis of colo-colic intussusception. This patient was
      successfully treated with enema and no pathological findings were identified via
      radiology. Laboratory results supported the presence of IgE-mediated allergy to
      salmon roe in the present patient. To our knowledge, this is the first report to
      describe the possible association between intussusception and a hypersensitive
      food reaction. 

PMID- 24134756
TI  - Novel CTSK mutation resulting in an entire exon 2 skipping in a Thai girl with
      pycnodysostosis.
AB  - Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by
      osteosclerosis, short stature, acro-osteolysis of the distal phalanges, bone
      fragility and skull deformities. Mutations in the cathepsin K (CTSK) gene, which
      encodes a lysosomal cysteine protease highly expressed in osteoclasts, have been
      found to be responsible for the disease. We identified a Thai girl with
      pycnodysostosis. Her parents were first cousins. Polymerase chain reaction
      sequencing of the entire coding regions of CTSK of the proband's complementary
      DNA revealed that the whole exon 2 was skipped. We subsequently amplified exon 2
      using genomic DNA, which showed that the patient was homozygous for a c.120G>A
      mutation. The mutation was located at the last nucleotide of exon 2. Its presence
      was confirmed by restriction enzyme analysis using BanI. The skipping of exon 2
      eliminates the normal start codon. The mutation has never been previously
      reported, thus the current report expands the CTSK mutational spectrum. 

PMID- 24134757
TI  - Continuous hemodialysis therapy for an extremely low-birthweight infant with
      hyperammonemia.
AB  - Hyperammonemia of newborns should be treated promptly, and the outcome depends on
      the rapid elimination of excessive plasma ammonia. We encountered a case of
      transient hyperammonemia in an extremely low-birthweight infant whose plasma
      ammonia decreased sufficiently after continuous hemodialysis therapy. It seems
      that continuous hemodialysis therapy using the peripheral artery and umbilical
      vein is useful for hyperammonemia of extremely low-birthweight infants; however,
      there are several problems to consider due to the immaturity of these infants. 

PMID- 24134758
TI  - Neonatal urethral polyps associated with Beckwith-Wiedemann syndrome.
AB  - We report the first case of Beckwith-Wiedemann syndrome without urinary
      obstruction, but with a congenital urethral polyp as a tumor protruding from the
      external urinary meatus. The present case suggests a possible relation between
      Beckwith-Wiedemann and the onset of fibroepithelial polyps in the reno-urinary
      system during the neonatal period. 

PMID- 24134759
TI  - Extremely rare cause of congenital diarrhea: enteric anendocrinosis.
AB  - Congenital diarrheal disorders consist of a variety of chronic enteropathies.
      There are approximately 30 different diseases that can be classified into four
      groups according to the mechanisms involved in pathogenesis: (i) absorption and
      transport of nutrients and electrolytes; (ii) enterocyte differentiation and
      polarization; (iii) enteroendocrine cell differentiation; and (iv) modulation of
      the intestinal immune response. Affected patients often present with life
      threatening diarrhea, in the first few weeks of life. A new disorder, enteric
      anendocrinosis, which is characterized by severe malabsorptive diarrhea and a
      lack of intestinal enteroendocrine cells has recently been described in six
      patients with recessively inherited mutations in the Neurogenin-3 gene. In this
      report we describe a seventh case with a review of the literature. 

PMID- 24134760
TI  - Paroxysmal cold hemoglobinuria caused by an IgM-class Donath-Landsteiner
      antibody.
AB  - We report on a 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH)
      following the first dose of a seven-valent pneumococcal conjugate vaccine. He was
      admitted because of dark urine after exposure to cold air. Laboratory tests
      indicated anemia, increased serum indirect bilirubin and lactate dehydrogenase,
      and decreased serum haptoglobin. Donath-Landsteiner (D-L) test was positive. The
      D-L antibody belonged to the IgM class and exhibited anti-P specificity. Symptoms
      and signs subsided after supportive care without any medication. Although PCH is
      often associated with viral or bacterial infection and is caused by IgG-class D-L
      antibodies with anti-P specificity, this case was unique because a D-L antibody
      of the IgM class with anti-P specificity caused PCH after immunization with a
      pneumococcal vaccine. 

PMID- 24134761
TI  - Benign transient hyperphosphatasemia associated with Epstein-Barr virus
      infection.

PMID- 24134762
TI  - Thrombolytic therapy in Kawasaki disease: a report of four cases.
AB  - Four patients with a thrombus in a coronary artery aneurysm due to Kawasaki
      disease (KD) were treated at our hospital between 1994 and 2009. All the cases
      were treated with intravenous coronary thrombolysis (IVCT) therapy and the cases
      with acute myocardial infarction were treated with additional intracoronary
      thrombolysis therapy. Although both thrombolytic therapies were effective, IVCT
      required more time than intracoronary thrombolysis to resolve the thrombus. We
      concluded that IVCT can be used as the first-line thrombolytic therapy for KD,
      except in cases with acute myocardial infarction. 

PMID- 24134763
TI  - Bilateral galactocele in a male infant with Down syndrome and congenital
      hypothyroidism.
AB  - Galactocele is an uncommon benign breast lesion. Its cause is unknown. Here, we
      report a male infant with Down syndrome and congenital hypothyroidism during the
      newborn period. At follow up, when he was 6 months old, bilateral mammillary
      swelling was detected and diagnosed as galactocele. Although thyroid hormone
      levels were normal, serum prolactin levels were elevated. Cyst aspiration was
      performed on the left side and 6 months after the aspiration of the cyst on the
      left side, both cysts had clinically and sonographically regressed. No recurrence
      was observed at the end of the 4th year. 

PMID- 24134764
TI  - Decreased portal vein flow during Kawasaki disease in a liver transplant patient.
AB  - Abnormalities of liver function tests are frequently documented in patients with
      Kawasaki disease, but the mechanism responsible for this has not yet been
      established. Described herein is the case of a 1-year-10-month-old girl who
      underwent liver transplantation at 11 months of age. Eleven months after
      transplantation the patient was diagnosed with Kawasaki disease, which was
      associated with some portal flow reduction, and received i.v. immunoglobulin,
      after which fever abated with improvement of portal flow to its pre-fever level.
      Abnormalities of liver function tests in Kawasaki disease patients may occur as a
      result of inflammation of both the biliary and portal systems. There are no
      reports on the potential relationship between Kawasaki disease and the portal
      vein, and accumulation of further data is necessary to better examine this
      relationship. 

PMID- 24134765
TI  - Young athlete with sudden cardiac arrest treated with therapeutic hypothermia.
AB  - Reported herein is a coronary anomaly that occurred in a young adolescent athlete
      who presented with cardiopulmonary arrest. The patient was resuscitated and
      treated with therapeutic hypothermia. The patient had no associated neurological
      complications at follow up. Enhanced computed tomography of the heart indicated
      an anomalous left main coronary artery originating from the right coronary sinus
      and coursing between the aorta and the pulmonary artery. The patient underwent
      surgical intervention with coronary artery bypass grafting to prevent symptom
      recurrence. 

PMID- 24134766
TI  - Splenic infarction in a child with primary Epstein-Barr virus infection.
AB  - Described herein is the case of a previously healthy 7-year-old girl who had
      splenic infarction. This lesion was identified 1 day after the first presentation
      of peri-umbilical and right upper quadrant pain. She had abnormal hepatic
      function and mild splenomegaly, and was diagnosed as having primary Epstein-Barr
      virus (EBV) infection. Coagulation profiles indicated low plasma activity of
      protein C (49%) and protein S (47%), which normalized 3 weeks later.
      Hypercoagulability in transient protein C and protein S deficiency might
      contribute to the development of splenic infarction in infectious mononucleosis. 

PMID- 24134767
TI  - Anaplastic sarcoma of the kidney: case report and literature review.
AB  - Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric
      renal tumor. The present patient, a 13-year-old boy with a large renal mass,
      underwent surgery. Pathological findings showed proliferation of short spindle
      shaped cells with anaplastic features including multiple foci in hyaline
      cartilage. Complex chromosomal abnormalities were detected in the tumor cells.
      Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete
      remission but the tumor recurred and the patient died during re-induction
      chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage.
      Because there were no viable tumor cells, the recurrent tumor was considered to
      have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown
      pathogenesis, and no standard treatment has yet been established, but the tumor
      cells may be responsive to chemotherapy. Further study is needed to establish the
      optimal treatment strategy. 

PMID- 24134768
TI  - Asthma and hemoglobinopathy: when is supplemental oxygen required?
AB  - Asthma is the most common reason for referral to the emergency department in
      childhood. In severe attacks, supplemental O2 is given when oxygen saturation
      level is <90%. Described herein is the case of a child with persistent low oxygen
      saturation as measured on pulse oximetry (S(p)O2) after full clinical recovery
      from an asthma attack. Simultaneously, P(a)O2 was normal. A diagnosis of abnormal
      hemoglobin with decreased oxygen affinity (hemoglobin Seattle) was made on
      hemoglobin electrophoresis and genetic analysis. To ascertain when supplemental
      oxygen was needed, an oxygen dissociation curve was plotted using the tonometer
      technique, and it was found that an S(p)O2 of 70% is parallel to a P(a)O2 of 60
      mmHg. Plotting an oxygen dissociation curve is a simple reproducible method to
      determine when supplemental oxygen is required for a child with a
      hemoglobinopathy.

PMID- 24134769
TI  - Post-streptococcal acute glomerulonephritis associated with pneumococcal
      infection.
AB  - Streptococcus pyogenes is the most common cause of post-infectious
      glomerulonephritis. Described herein is the case of a 5-year-old girl with
      febrile post-streptococcal acute glomerulonephritis (PSAGN) associated with
      pneumococcal bacteremia. The chief complaints were fever and macrohematuria
      without respiratory symptoms. Urinalysis indicated a protein level of 3+.
      Serological data showed elevated anti-streptolysin O (ASO) and
      hypocomplementemia. Blood culture was positive for S. pneumoniae. Her acute renal
      failure was mild and improved over several days. Although PSAGN was confirmed by
      elevated ASO and transient hypocomplementemia, the clinical course was consistent
      with those of several reported cases of AGN associated with pneumococcal
      infection. To our knowledge, there have been few reports on the relationship
      between pneumococcal infection and the incidence of PSAGN. We suggest the
      hypothesis that pneumococcal infection itself could exaggerate the complement
      reaction leading to PSAGN. It is important to consider PSAGN associated with a
      microbial infection such as S. pneumoniae when faced with a febrile patient with
      AGN.

PMID- 24134770
TI  - Efficacy of recombinant human soluble thrombomodulin for childhood hemolytic
      uremic syndrome.
AB  - Recombinant human soluble thrombomodulin (rhTM) is a promising therapeutic
      natural anticoagulant and is used clinically for the treatment of disseminated
      intravascular coagulation (DIC). Herein is reported the cases of two HUS children
      treated with rhTM. The patients were diagnosed as having typical HUS on the basis
      of thrombocytopenia, hemolytic anemia, acute renal failure, and the detection
      Escherichia coli 0157. I.v. rhTM was started as an anti-coagulant drug. At 2 days
      after the first treatment in both patients, fibrin/fibrinogen degradation
      products and d-dimer levels were significantly decreased, and there was a
      subsequent slight improvement in thrombocytopenia, and a decrease in serum
      lactate dehydrogenase level. Urinary protein excretion gradually diminished and a
      decrease in serum creatinine level was observed. The patients did not require
      dialysis therapy. The present results suggest that rhTM may be a safe and
      effective treatment for DIC complicated with HUS in children. 

PMID- 24134771
TI  - Glatiramer acetate treatment effects on gene expression in monocytes of multiple
      sclerosis patients.
AB  - BACKGROUND: Glatiramer acetate (GA) is a mixture of synthetic peptides used in
      the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The
      aim of this study was to investigate the effects of GA therapy on the gene
      expression of monocytes. METHODS: Monocytes were isolated from the peripheral
      blood of eight RRMS patients. The blood was obtained longitudinally before the
      start of GA therapy as well as after one day, one week, one month and two months.
      Gene expression was measured at the mRNA level by microarrays. RESULTS: More than
      400 genes were identified as up-regulated or down-regulated in the course of
      therapy, and we analyzed their biological functions and regulatory interactions.
      Many of those genes are known to regulate lymphocyte activation and
      proliferation, but only a subset of genes was repeatedly differentially expressed
      at different time points during treatment. CONCLUSIONS: Overall, the observed
      gene regulatory effects of GA on monocytes were modest and not stable over time.
      However, our study revealed several genes that are worthy of investigation in
      future studies on the molecular mechanisms of GA therapy.

PMID- 24134772
TI  - Editorial for 'randomized controlled trial assessing the effect of simvastatin in
      primary biliary cirrhosis'.

PMID- 24134774
TI  - Touch displays: the effects of palm rejection technology on productivity,
      comfort, biomechanics and positioning.
AB  - Direct touch displays can improve the human-computer experience and productivity;
      however, the higher hand locations may increase shoulder fatigue. Palm rejection
      (PR) technology may reduce shoulder loads by allowing the palms to rest on the
      display and increase productivity by registering the touched content and
      fingertips through the palms rather than shoulders. The effects of PR were
      evaluated by having participants perform touch tasks while posture and reaction
      force on the display were measured. Enabling PR, during which the subjects could
      place the palms on the display (but were not required to), resulted in increased
      wrist extension, force applied to the display and productivity, and less
      discomfort, but had no effect on the self-selected positioning of the display.
      Participants did not deliberately place their palms on the display; therefore,
      there was no reduction in shoulder load and the increased productivity was not
      due to improved hand registration. The increased productivity may have been due
      to reduced interruptions from palm contacts or reduced motor control demands. 

PMID- 24134775
TI  - Removing antinutrients from rapeseed press-cake and their benevolent role in
      waste cooking oil-derived biodiesel: conjoining the valorization of two disparate
      industrial wastes.
AB  - Valorization of oilseed processing wastes is thwarted due to the presence of
      several antinutritional factors such as phenolics, tannins, glucosinolates, allyl
      isothiocyanates, and phytates; moreover, literature reporting on their
      simultaneous extraction and subsequent practical application is scanty. Different
      solvent mixtures containing acetone or methanol pure or combined with water or an
      acid (hydrochloric, acetic, perchloric, trichloroacetic, phosphoric) were tested
      for their efficiency for extraction of these antinutritive compounds from
      rapeseed press-cake. Acidified extraction mixtures (nonaqueous) were found to be
      superior to the nonacidified ones. The characteristic differences in the efficacy
      of these wide varieties of solvents were studied by principal component analysis,
      on the basis of which the mixture 0.2% perchloric acid in methanol/acetone (1:1
      v/v) was deemed as "the best" for detoxification of rapeseed meal. Despite its
      high reductive potential, hemolytic activity of the extract from this solvent
      mixture clearly indicated the toxicity of the above-mentioned compounds on
      mammalian erythrocytes. Because of the presence of a high amount of antinutritive
      antioxidants, the study was further extended to examine the influence of this
      solvent extract on the stability of waste cooking oil-derived biodiesel.
      Treatment with the extract harbored significant improvement (p < 0.05) in the
      induction periods and pronounced reduction in microbial load of stored biodiesel
      investigated herein. Thus, a suitable solvent system was devised for removing the
      major antinutrients from rapeseed press-cake, and the solvent extract can,
      thereafter, be used as an effective exogenous antioxidant for biodiesel. In other
      words, integrated valorization of two different industrial wastes was
      successfully achieved. 

PMID- 24134773
TI  - Effect of hospital-SNF referral linkages on rehospitalization.
AB  - OBJECTIVE: To determine whether the rate of rehospitalization is lower among
      patients discharged to skilled nursing facilities (SNFs) with which a hospital
      has a strong linkage. DATA SOURCES/COLLECTION: We used national Medicare
      enrollment, claims, and the Minimum Data Set to examine 2.8 million newly
      discharged patients to 15,063 SNFs from 2,477 general hospitals between 2004 and
      2006. STUDY DESIGN: We examined the relationship between the proportion of
      discharges from a hospital and alternative SNFs on the rehospitalization of
      patients treated by that hospital-SNF pair using an instrumental variable
      approach. We used distances to alternative SNFs from residence of the patients of
      the originating hospital as the instrument. PRINCIPAL FINDINGS: Our estimates
      suggest that if the proportion of a hospital's discharges to an SNF was to
      increase by 10 percentage points, the likelihood of patients treated by that
      hospital-SNF pair to be rehospitalized within 30 days would decline by 1.2
      percentage points, largely driven by fewer rehospitalizations within a week of
      hospital discharge. CONCLUSIONS: Stronger hospital-SNF linkages, independent of
      hospital ownership, were found to reduce rehospitalization rates. As hospitals
      are held accountable for patients' outcomes postdischarge under the Affordable
      Care Act, hospitals may steer their patients preferentially to fewer SNFs.

PMID- 24134776
TI  - Detection of cobalt in synovial fluid from metal-on-metal hip prosthesis:
      correlation with the ion haematic level.
AB  - Hip replacement with large metal-on-metal (MoM) coupling has recently been under
      attention for its metal ions release, inducing several disorders. Since the blood
      level toxicity threshold for cobalt is known, the aim of this work is to
      determine whether Co serum and blood levels correlate with the synovial fluid
      level. Beside this, the synovial fluid Co from patients without prosthesis has
      also been measured. Co has been determined in 54 samples (32 unilateral MoM and
      22 controls) with inductively coupled plasma mass spectrometry in the three
      matrices. In the prosthesized group, cobalt was significantly higher compared
      with controls and in the synovial fluid it strongly correlated with whole blood
      Co (p = 0.847) and serum (p = 0.855). Moreover, the Co levels into whole blood
      and serum were significantly different. In conclusion, haematic Co concentration
      correctly reflects Co local level.

PMID- 24134777
TI  - Autologous stem cell transplant can overcome poor prognosis in patients with
      multiple myeloma with extramedullary plasmacytoma.

PMID- 24134778
TI  - Sensitivity and specificity of cerebrospinal fluid flow cytometry for the
      diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma.
AB  - The presence of leukemic blasts detected by light microscopy in cerebrospinal
      fluid (CSF) establishes the diagnosis of leukemic meningitis in acute
      lymphoblastic leukemia/lymphoma (ALL). Flow cytometry immunophenotyping (FCI) is
      a very sensitive method that detects a minute number of aberrant cells, and is
      increasingly performed on CSF samples. We sought to determine the sensitivity and
      specificity of CSF FCI for the diagnosis of leukemic meningitis in ALL. Between
      November 2007 and August 2011, 800 CSF samples from 80 patients with ALL were
      available from diagnostic lumbar punctures (LPs; n = 80), follow-up LPs (n = 687)
      and at the time of relapse (n = 33). FCI was performed on 267 samples, and only
      identified aberrant cells in cytologically confirmed cases of leukemic
      meningitis. A blinded review of all cases with detectable CSF nucleated cells
      confirmed these findings. We conclude that CSF FCI has a 100% sensitivity and
      specificity for the detection of lymphoblasts. However, additional studies are
      needed to define the role this procedure plays in the diagnosis of leukemic
      meningitis.

PMID- 24134779
TI  - Using syndromic surveillance to estimate baseline rates for healthcare-associated
      infections in critical care units of small animal referral hospitals.
AB  - BACKGROUND: Expected rates of healthcare-associated infections (HCAI) have not
      been established in veterinary hospitals. Baseline rates are critically needed as
      benchmarks for quality animal care. OBJECTIVE: To estimate the occurrence of
      events related to HCAI identified using a standardized syndromic surveillance
      system in small animals in critical care cases at referral hospitals. ANIMALS:
      Weaned dogs and cats (n = 1,951) that were hospitalized in the critical care unit
      of referral teaching hospitals during a 12-week period. METHODS: Multicenter,
      prospective longitudinal study. A survey was completed for all enrolled animals
      to record basic demographics, information about procedures and treatments that
      animals received, and to document the occurrence of defined nosocomial syndromes.
      Data were analyzed to identify risk factors associated with the occurrence of
      these nosocomial syndromes. RESULTS: Controlling for hospital of admission, 16.3%
      of dogs (95% confidence intervals [CI], 14.3-18.5) and 12% of cats (95% CI, 9.3
      15.5) were reported to have had >= 1 nosocomial syndrome occur during
      hospitalization. Risk factors found to have a positive association with the
      development of a nosocomial syndrome were longer hospital stays, placement of a
      urinary catheter, surgical procedures being performed, and the administration of
      antiulcer medications and antimicrobial drugs excluding those given
      perioperatively. CONCLUSIONS AND CLINICAL IMPORTANCE: Syndromic surveillance
      systems can be successfully standardized for use across multiple hospitals to
      effectively collect data pertinent to HCAI rates and risk factors for occurrence.

PMID- 24134780
TI  - Public health aspects of snakebite care in West Africa: perspectives from
      Nigeria.
AB  - Snakebite envenoming is a major public health problem among rural communities of
      the Nigerian savanna. The saw-scaled or carpet viper (Echis ocellatus) and, to a
      lesser extent, the African cobras (Naja spp.) and puff adders (Bitis arietans)
      have proved to be the most important cause of mortality and morbidity. The main
      clinical features of E. ocellatus envenoming are systemic hemorrhage,
      incoagulable blood, shock, local swelling, bleeding and, occasionally, necrosis.
      Bites may be complicated by amputation, blindness, disability, disfigurement,
      mutilation, tissue destruction and psychological consequences. Antivenom remains
      the hallmark and mainstay of envenoming management while studies in Nigeria
      confirm its protection of over 80% against mortality from carpet-viper bites.
      However, the availability, distribution and utilization of antivenom remain
      challenging although two new antivenoms (monospecific EchiTab G and trispecific
      EchiTab ICP-Plus) derived from Nigerian snake venoms have proven very effective
      and safe in clinical trials. A hub-and-spoke strategy is suggested for broadening
      antivenom access to endemic rural areas together with instituting quality
      assurance, standardization and manpower training. With the advent of
      antivenomics, national health authorities must be aided in selecting and
      purchasing antivenoms appropriate to their national needs while manufacturers
      should be helped in practical ways to improve the safety, efficacy and potential
      coverage against snake venoms and pricing of their products. 

PMID- 24134781
TI  - A dual role for the inducer in signalling by MalT, a signal transduction ATPase
      with numerous domains (STAND).
AB  - Signal transduction ATPases with numerous domains (STAND) are widespread
      proteins, whose activation involves inducer-dependent conversion of resting ADP
      bound monomers into active ATP-bound multimers. This process notably comprises
      opening of the nucleotide-binding oligomerization domain (NOD), nucleotide
      exchange and NOD-mediated multimerization. How inducer binding to the sensor
      domain, whose structure is not conserved throughout the STAND family, causes
      protein activation remains unclear. We used MalT, an Escherichia coli
      transcription factor, as a STAND model system, to address this question by
      dissecting the signalling pathway in vitro. We have found that inducer binding to
      the sensor is the first step of the activation pathway. It both triggers opening
      of the NOD and makes the MalT multimer competent for binding promoter MalT sites
      via its DNA-binding domains. Based on available data, we proposed that inducer
      trigger of NOD opening is a conserved STAND feature, irrespective of the sensor
      structure. As discussed, an additional role for the inducer, as found for MalT,
      might pertain to other types of STANDs. 

PMID- 24134782
TI  - Akaeolide, a carbocyclic polyketide from marine-derived Streptomyces.
AB  - Akaeolide, a novel polycyclic polyketide, was isolated from the culture extract
      of a marine-derived actinomycete belonging to the genus Streptomyces. The planar
      structure of the new compound was elucidated by spectroscopic analysis including
      NMR and MS, and the absolute configuration was determined by X-ray
      crystallographic analysis of its chlorinated derivative. Akaeolide possesses a 15
      membered carbocyclic framework, apparently derived from the malonate pathway,
      with a tetrahydrofuran ring and a beta-keto-delta-lactone unit. 

PMID- 24134784
TI  - Tissue hypoxia in pathogenesis of ulcerative colitis: should we change all our
      beliefs?

PMID- 24134783
TI  - Monocyte implication in renal allograft dysfunction.
AB  - Macrophages are involved in the development and progression of kidney fibrosis.
      The aim of this study was to analyse the phenotype of circulating monocytes and
      their ability to predict kidney allograft dysfunction in living kidney transplant
      recipients. Whole blood samples from 25 kidney recipients and 17 donors were
      collected at five time-points. Monocyte phenotype was analysed by flow cytometry,
      and interleukin (IL)-10 and soluble CD163 by enzyme-linked immunosorbent assay.
      One week after transplantation, surface CD163 and IL-10 levels increased
      significantly from baseline [2.99 +/- 1.38 mean fluorescence intensity (MFI) to
      5.18 +/- 2.42 MFI for CD163; 4.5 +/- 1.46 pg/ml to 6.7 +/- 2.5 pg/ml for IL-10].
      This CD163 increase correlated with 4-month creatinine levels (r = 0.4394, P =
      0.04). However, soluble CD163 decreased significantly from baseline at 1 week
      (797.11 +/- 340.45 ng/ml to 576.50 +/- 293.60 ng/ml). CD14(+) CD16(-) monocytes
      increased at 4 months and correlated positively with creatinine levels at 12 and
      24 months (r = 0.6348, P = 0.002 and r = 0.467, P = 0.028, respectively) and
      negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r =
      0.6056, P = 0.003). At 4 months, IL-10 decreased significantly (P = 0.008) and
      correlated positively with creatinine at 2 years (r = 0.68, P = 0.010) and with
      CD14(+) CD16(-) monocytes at 4 months (r = 0.732, P = 0.004). At 24 h, levels of
      human leucocyte antigen D-related declined from 12.12 +/- 5.99 to 5.21 +/- 3.84
      and CD86 expression decreased from 2.76 +/- 1.08 to 1.87 +/- 0.95. Both markers
      recovered progressively until 12 months, when they decreased again. These results
      indicate that monitoring monocytes could be a promising new prognostic tool of
      graft dysfunction in renal transplant patients. 

PMID- 24134785
TI  - Topical immunomodulation with diphenylcyclopropenone for alopecia areata: the
      Lebanese experience.
AB  - Topical immunotherapy with diphenylcyclopropenone (DPCP) is a treatment that can
      be used in patients with alopecia areata (AA) with more than 50% involvement of
      the scalp. The aim of this study is to assess the response of our patients with
      AA treated with topical immunotherapy with DPCP at the American University of
      Beirut-Medical Center (AUB-MC) and to characterize the favorable prognostic
      factors that predict response to treatment. This is a retrospective study of all
      patients diagnosed with AA at AUB-MC and treated with topical immunotherapy with
      DPCP over a period of 10 years. A total of 34 cases were included for analysis
      (19 males and 15 females). The majority of patients had limited AA (58.8%) with a
      mean of 39% of scalp involvement. The remaining patients had alopecia universalis
      (29.4%) and alopecia totalis (11.8%). The percentage of patients that responded
      to DPCP therapy in our series was 79.4% (n = 27). Ten patients achieved a maximal
      grade of 3 following treatment, six patients only achieved a grade of 1, and six
      patients achieved a grade of 2. Only five of the patients who responded to
      therapy achieved a grade of 4. Of the patients who responded, 10 relapsed
      (29.4%), and the mean time to relapse was 74.6 weeks from the initiation of
      treatment. No specific favorable prognostic factors were identified to predict
      response to treatment; however, a negative family history of atopy was found to
      be protective against relapse (P = 0.020). The most common side effect of therapy
      was itching (85.3%), followed by contact dermatitis (58.8%), blistering (17.6%),
      and cervical lymphadenopathy (17.6%). Limitations of this study were the
      retrospective nature of the study and the limited number of patients. This is, to
      the best of our knowledge, the first study on topical immunotherapy with DPCP in
      patients with extensive AA from a Middle Eastern population. This modality of
      treatment is effective in inducing a response in patients with extensive AA,
      although the response is partial in the majority of the cases. Benefits should be
      weighed against the high side-effect profile of therapy before initiation of
      treatment.

PMID- 24134786
TI  - Chronic high dose intraperitoneal bisphenol A (BPA) induces substantial
      histological and gene expression alterations in rat penile tissue without
      impairing erectile function.
AB  - INTRODUCTION: Bisphenol A (BPA), released from plastics and dental sealants, is a
      suspected endocrine disruptor and reproductive toxicant. In occupationally
      exposed workers, BPA has been associated with erectile dysfunction (ED). AIMS: To
      determine whether long-term exposure to high doses of BPA in the rat affects
      serum levels of testosterone (T) and estradiol (E2), and induces corporal
      histopathology and resultant ED. METHODS: Young rats were injected
      intraperitoneal (IP) injection daily with BPA at 25 mg/kg/day or vehicle (n =
      8/group). Erectile function was measured at 3 months by cavernosometry and
      electrical field stimulation (EFS). BPA was assayed in serum, urine, and penile
      tissue, and serum T and E2 were determined. Quantitative Masson trichrome,
      terminal deoxynucleotidyl transferase dUTP nick end labeling, Oil Red O,
      immunohistochemistry for calponin, alpha-smooth muscle actin, and Oct 4 were
      applied to penile tissue sections. Protein markers were assessed by Western blots
      and 2-D minigels, and RNA by DNA microarrays. MAIN OUTCOME MEASURES: Erectile
      function, histological, and biochemical markers in corporal tissue. RESULTS: In
      the BPA-treated rats, total and free BPA levels were increased in the serum,
      urine, and penile tissue while serum T and E2 levels were reduced. In addition,
      the corpora cavernosa demonstrated a reduction in smooth muscle (SM) content,
      SM/collagen ratio, together with an increase in myofibroblasts, fat deposits, and
      apoptosis, but no significant change in collagen content or stem cells
      (nuclear/perinuclear Oct 4). In the penile shaft, BPA induced a downregulation of
      Nanog (stem cells), neuronal nitric oxide synthase (nitrergic terminals), and
      vascular endothelial growth factor (angiogenesis), with genes related to SM tone
      and cytoskeleton upregulated 5- to 50-fold, accompanied by changes in the
      multiple protein profile. However, both cavernosometry and EFS were unaltered by
      BPA. CONCLUSIONS: While rats treated chronically with a high IP dose of BPA
      developed hypogonadism and a corporal histo- and molecular-pathology usually
      associated with ED, no changes were detected in erectile function as measured by
      EFS and cavernosometry. Further studies using alternate routes of BPA
      administration with various doses and length of exposure are needed to expand
      these findings.

PMID- 24134788
TI  - Could investment in preventive health care services reduce health care costs
      among those insured with health insurance societies in Japan?
AB  - This study examined the impact of expenditures for preventive health care
      services on health care costs among those insured with health insurance societies
      in Japan using cross-sectional and longitudinal designs. The subjects of the
      study were those insured with Japan's 1481 health insurance societies belonging
      to the National Federation of Health Insurance Societies in 2003 and 2007.
      Multiple regression analyses were conducted using the forced entry method. Case
      rates, number of service days, and health care costs were used as dependent
      variables, and preventive health care expenditures, average age, number of the
      insured, gender ratio, average monthly salary, and dependents ratio were used as
      independent variables. Expenditures for preventive health care services showed
      significant negative correlations with both the number of service days and health
      care costs for inpatient and outpatient services in 2003 and 2007. The results
      showed that expenditures for preventive health care services had a negative
      relationship with health care costs. Thus, these findings support the effects of
      investment in preventive health activities as promoted by health insurance
      societies to reduce health care costs.

PMID- 24134787
TI  - Genome-level analyses of Mycobacterium bovis lineages reveal the role of SNPs and
      antisense transcription in differential gene expression.
AB  - BACKGROUND: Bovine tuberculosis (bTB) is a disease with major implications for
      animal welfare and productivity, as well as having the potential for zoonotic
      transmission. In Great Britain (GB) alone, controlling bTB costs in the region of
      L 100 million annually, with the current control scheme seemingly unable to stop
      the inexorable spread of infection. One aspect that may be driving the epidemic
      is evolution of the causative pathogen, Mycobacterium bovis. To understand the
      underlying genetic changes that may be responsible for this evolution, we
      performed a comprehensive genome-level analyses of 4 M. bovis strains that
      encompass the main molecular types of the pathogen circulating in GB. RESULTS: We
      have used a combination of genome sequencing, transcriptome analyses, and
      recombinant DNA technology to define genetic differences across the major M.
      bovis lineages circulating in GB that may give rise to phenotypic differences of
      practical importance. The genomes of three M. bovis field isolates were sequenced
      using Illumina sequencing technology and strain specific differences in gene
      expression were measured during in vitro growth and in ex vivo bovine alveolar
      macrophages using a whole genome amplicon microarray and a whole genome tiled
      oligonucleotide microarray. SNP/small base pair insertion and deletions and gene
      expression data were overlaid onto the genomic sequence of the fully sequenced
      strain of M. bovis 2122/97 to link observed strain specific genomic differences
      with differences in RNA expression. CONCLUSIONS: We show that while these strains
      show extensive similarities in their genetic make-up and gene expression
      profiles, they exhibit distinct expression of a subset of genes. We provide
      genomic, transcriptomic and functional data to show that synonymous point
      mutations (sSNPs) on the coding strand can lead to the expression of antisense
      transcripts on the opposing strand, a finding with implications for how we define
      a 'silent' nucleotide change. Furthermore, we show that transcriptomic data based
      solely on amplicon arrays can generate spurious results in terms of gene
      expression profiles due to hybridisation of antisense transcripts. Overall our
      data suggest that subtle genetic differences, such as sSNPS, may have important
      consequences for gene expression and subsequent phenotype.

PMID- 24134789
TI  - Double-positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical
      profile.
AB  - Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T-cell
      lymphoma (CTCL), and tumor cells typically express a mature T-helper memory
      phenotype. A minority of MF patients display an unusual phenotype, which may be
      either CD4(-)/CD8(+) or double negative. Herein, we report a case of biopsy
      proven MF in a 31-year-old woman who presented with infiltrated plaques involving
      photoprotected areas of the skin. Immunohistochemical study combined with
      confocal microscopy revealed co-expression of CD4 and CD8 in a subset of atypical
      T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual
      positive MF. 

PMID- 24134790
TI  - Neurobehavioural correlates in older children and adolescents with obesity and
      obstructive sleep apnoea.
AB  - AIM: The relationship between obstructive sleep apnoea (OSA) and poorer
      neurobehavioural outcomes in school-age children is well established, but the
      relationship in obese children and adolescents, in whom OSA is more common, is
      not so well established. We aimed to investigate this relationship in 10-18-year
      olds. METHODS: Thirty-one participants with a mean body mass index (BMI) of 32.3
      +/- 4.9 enrolled. BMI-for-age cut-offs were used to define obesity. Participants
      underwent polysomnography and were classified into OSA (apnoea-hypopnoea index
      (AHI) > 2 per hour) and non-OSA (AHI <= 2) groups. Intelligence, memory and
      learning, academic achievement, behaviour and executive functioning were assessed
      using the Wechsler Abbreviated Scale of Intelligence, Wide Range Assessment of
      Memory and Learning 2, Wechsler Individual Achievement Test II (WIAT-II),
      Behavioural Assessment System for Children 2 and Behaviour Rating Inventory of
      Executive Function, respectively. RESULTS: Forty-eight per cent (15/31) were
      classified as having OSA, and 52% (16/31) as non-OSA. The obese cohort performed
      below the average of normative data on several neurobehavioural measures. WIAT-II
      maths scores were significantly lower (P = 0.034) in the OSA group than in the
      non-OSA group (means 84.5 vs. 94.6, respectively), losing significance after
      adjustment for IQ, age and gender. Self-reported school problems were
      significantly worse in the OSA group before and after multivariate adjustment (P
      = 0.010, Cohen's d = 1.02). No other significant differences were found.
      CONCLUSIONS: Results suggest that OSA may increase risk for some poorer
      educational and behavioural outcomes. The findings are reasonably consistent with
      and add to the evidence base of the few studies that have explored this
      relationship.

PMID- 24134791
TI  - Understanding heterogeneity in social anxiety disorder: dependency and self
      criticism moderate fear responses to interpersonal cues.
AB  - OBJECTIVE: This study examined how the personality traits of self-criticism and
      dependency moderated the effects of situational interpersonal cues on fear during
      interpersonal interactions among individuals with social anxiety disorder (SAD).
      We hypothesized that self-criticism would moderate the fear-inducing effects of
      situational self-consciousness and that dependency would moderate the fear
      inducing effects of situational emotional insecurity. METHODS: Forty SAD patients
      (Mage = 29.23) and matched community controls (Mage = 28.93) completed event
      contingent record forms after each significant social interaction of over 5 min
      for a 20-day period. There were 20 female patients and 20 male patients in each
      group. RESULTS: Event-level self-consciousness was more strongly associated with
      elevations in fear among socially anxious patients who reported higher levels of
      self-criticism, while event-level emotional security was more strongly associated
      with decreases in fear among SAD patients who reported higher levels of
      dependency. These interactions were not found in the community sample.
      CONCLUSIONS: Findings support the application of personality-vulnerability models
      to understanding fear during social interactions in patients with SAD. Results
      also have implications for psychotherapeutic treatments of SAD.

PMID- 24134792
TI  - Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa
      isolated from contact lenses in Karachi-Pakistan.
AB  - BACKGROUND: The contaminated contact lens provides Pseudomonas aeruginosa an
      ideal site for attachment and biofilm production. Continuous contact of the eye
      to the biofilm-infested lens can lead to serious ocular diseases, such as
      keratitis (corneal ulcers). The biofilms also prevent effective penetration of
      the antibiotics, which increase the chances of antibiotic resistance. METHODS:
      For this study, 22 Pseudomonas aeruginosa isolates were obtained from 36 contact
      lenses and 14 contact lens protective fluid samples. These isolates were tested
      against eight commonly used antibiotics using Kirby-Bauer disk diffusion method.
      The biofilm forming potential of these isolates was also evaluated using various
      qualitative and quantitative techniques. Finally, a relationship between biofilm
      formation and antibiotic resistance was also examined. RESULTS: The isolates of
      Pseudomonas aeruginosa tested were found resistant to most of the antibiotics
      tested. Qualitative and quantitative biofilm analysis revealed that most of the
      isolates exhibited strong biofilm production. The biofilm production was
      significantly higher in isolates that were multi-drug resistant (p < 0.0001).
      CONCLUSION: Our study indicates that multi-drug resistant, biofilm forming
      Pseudomonas aeruginosa isolates are mainly involved in contact lens associated
      infections. This appears to be the first report from Pakistan, which analyzes
      both antibiotic resistance profile and biofilm forming potential of Pseudomonas
      aeruginosa isolates from contact lens of the patients with contact lens
      associated infections.

PMID- 24134793
TI  - Clinical, laboratory and molecular signs of immunodeficiency in patients with
      partial oculo-cutaneous albinism.
AB  - Hypopigmentation disorders that are associated with immunodeficiency feature both
      partial albinism of hair, skin and eyes together with leukocyte defects. These
      disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS)
      and MAPBP-interacting protein deficiency syndromes. These are heterogeneous
      autosomal recessive conditions in which the causal genes encode proteins with
      specific roles in the biogenesis, function and trafficking of secretory
      lysosomes. In certain specialized cells, these organelles serve as a storage
      compartment. Impaired secretion of specific effector proteins from that
      intracellular compartment affects biological activities. In particular, these
      intracellular granules are essential constituents of melanocytes, platelets,
      granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus,
      abnormalities affect pigmentation, primary hemostasis, blood cell counts and
      lymphocyte cytotoxic activity against microbial pathogens. Among eight
      genetically distinct types of HPS, only type 2 is characterized by
      immunodeficiency. Recently, a new subtype, HPS9, was defined in patients
      presenting with immunodeficiency and oculocutaneous albinism, associated with
      mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with
      recurrent childhood bacterial or viral infections suggests syndromic albinism. T
      and NK cell cytotoxicity are generally impaired in patients with these disorders.
      Specific clinical and biochemical phenotypes can allow differential diagnoses
      among these disorders before molecular testing. Ocular symptoms, including
      nystagmus, that are usually evident at birth, are common in patients with HPS2 or
      CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP)
      deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a
      diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term
      complication of CHS, but is uncommon in other syndromic albinism. Chronic
      neutropenia is a feature of HPS2 and MAPBPIP-deficiency syndrome, whereas it is
      usually transient in CHS and GS2. In every patient, an accurate diagnosis is
      required for prompt and appropriate treatment, particularly in patients who
      develop HLH or in whom bone marrow transplant is required. This review describes
      the molecular and pathogenetic mechanisms of these diseases, focusing on clinical
      and biochemical aspects that allow early differential diagnosis.

PMID- 24134794
TI  - Enhancement in deposition and permeation of 5-fluorouracil through human
      epidermis assisted by peptide dendrimers.
AB  - Enhancing the deposition and permeation of 5-fluorouracil across human epidermis
      assisted by appropriately charged and well-defined peptide dendrimers was
      investigated. Peptide dendrimers with arginine as the terminal amino acid and
      having a range of terminal positive charges (4(+), 8(+) and 16(+)) were
      synthesized by solid phase peptide synthesis. Various parameters including effect
      of peptide dendrimers on the solubility and partition coefficient of 5-FU,
      degradation of drug in skin as well as deposition and permeation of 5-FU
      in/through skin were studied. All the tested dendrimers increased the aqueous
      solubility and partition coefficient of 5-FU with each also significantly (p <
      0.05) enhancing the deposition and permeation of 5-FU in/across human epidermis
      in a concentration-dependent manner. Of the three peptide dendrimers examined, R8
      dendrimer (bearing 8(+) charge derived from four terminal arginines and MW of
      ~1000 Da) showed greatest values for flux, Q(48) (cumulative amount of drug
      permeated at the end of 48 h) and amount of drug retained in human skin.
      Furthermore, this study also scrutinized and reports on the likely mechanisms by
      which peptide dendrimers act as transdermal permeation enhancers.

PMID- 24134796
TI  - Translating pharmacogenomics discoveries into the clinic: an implementation
      framework.
AB  - The implementation of pharmacogenomics-guided care has the potential to improve
      clinical outcomes; however, the adoption of pharmacogenomics into clinical
      practice remains slow. This is partly due to the lack of a standardized framework
      for translating key findings into diagnostic tests. A recent study describes a
      comprehensive system developed by the Coriell Personalized Medicine Collaborative
      for facilitating the translation of genomic findings into clinical practice, and
      its application for seven commonly prescribed drugs. See related Research paper,
      http://genomemedicine.com/content/5/10/93. 

PMID- 24134795
TI  - Chronic venous leg ulcer treatment: future research needs.
AB  - The prevalence and costs of chronic venous ulcer care in the US are increasing.
      The Johns Hopkins University Evidence-Based Practice Center recently completed a
      systematic review of the comparative effectiveness of advanced wound dressings,
      antibiotics, and surgical management of chronic venous ulcers. Of 10,066
      citations identified in the literature search, only 66 (0.06%) met our liberal
      inclusion criteria for providing evidence on the effectiveness of interventions
      for chronic venous ulcers. Based on review of those studies, members of our team
      and a panel of informed stakeholders identified important research gaps and
      methodological deficiencies and prioritized specific future research needs. Based
      on that review, we provide the results of our assessment of future research needs
      for chronic venous ulcer care. Advanced wound dressings were considered to have
      the highest priority for future research, followed by venous surgery and
      antibiotics. An imperative from our assessment is that future research evaluating
      interventions for chronic venous ulcers meet quality standards. In a time of
      increasing cost pressure, the wound care community needs to develop high-quality
      evidence to justify the use of present and future therapeutic modalities. 

PMID- 24134797
TI  - Using quantile regression to examine health care expenditures during the Great
      Recession.
AB  - OBJECTIVE: To examine the association between the Great Recession of 2007-2009
      and health care expenditures along the health care spending distribution, with a
      focus on racial/ethnic disparities. DATA SOURCES/STUDY SETTING: Secondary data
      analyses of the Medical Expenditure Panel Survey (2005-2006 and 2008-2009). STUDY
      DESIGN: Quantile multivariate regressions are employed to measure the different
      associations between the economic recession of 2007-2009 and health care
      spending. Race/ethnicity and interaction terms between race/ethnicity and a
      recession indicator are controlled to examine whether minorities encountered
      disproportionately lower health spending during the economic recession. PRINCIPAL
      FINDINGS: The Great Recession was significantly associated with reductions in
      health care expenditures at the 10th-50th percentiles of the distribution, but
      not at the 75th-90th percentiles. Racial and ethnic disparities were more
      substantial at the lower end of the health expenditure distribution; however, on
      average the reduction in expenditures was similar for all race/ethnic groups. The
      Great Recession was also positively associated with spending on emergency
      department visits. CONCLUSION: This study shows that the relationship between the
      Great Recession and health care spending varied along the health expenditure
      distribution. More variability was observed in the lower end of the health
      spending distribution compared to the higher end.

PMID- 24134798
TI  - Odontogenic cutaneous fistulas: clinical and epidemiologic characteristics of 75
      cases.
AB  - BACKGROUND: Odontogenic cutaneous fistulas arise as a sequel of bacterial
      invasion of the dental pulp, become necrotic, and infection spreads into the
      periradicular area resulting in dissection and breakthrough to form sinus tracts
      that drain towards the skin. The objective of this study was to investigate the
      clinical and epidemiologic characteristics of patients diagnosed with odontogenic
      cutaneous fistulas. METHODS: A retrospective study was done between January 2001
      and December 2011. Cases were included with a clinical and radiological diagnosis
      of odontogenic cutaneous fistulas. The variables investigated were frequency,
      gender, age, localization, morphology, time of evolution, and referral clinical
      diagnosis. Data were analyzed using descriptive statistical methods. RESULTS:
      During an 11-year period, 75 cases were found. Female gender predominated with
      53% of the cases, and the mean age was 45 +/- 26 years. The most frequent
      location was the mandible angle, in 36% of the cases, and the most common
      morphology was a nodule, in 52%. The mean time of evolution was 8 +/- 11 months.
      The referral clinical diagnosis was odontogenic cutaneous fistulas in 51% of the
      cases. CONCLUSIONS: Our results are similar to those previously published-the
      diagnosis was suspected in only half of the cases. We consider it important that
      odontogenic cutaneous fistulas be included among the differential diagnosis of
      cutaneous facial lesions to avoid delaying appropriate treatment.

PMID- 24134799
TI  - Electron microscopy of astrocyte changes and subtypes in traumatic human
      edematous cerebral cortex: a review.
AB  - The astrocyte subtypes in moderate and severe human brain trauma complicated with
      subdural hematoma or hygroma are described. Clear and dense edematous and
      hypertrophic reactive astrocytes are distinguished in severe vasogenic brain
      edema. Swollen perineuronal astrocytes appear compressing and indenting dark,
      degenerated pyramidal and nonpyramidal nerve cells. Glycogen-depleted and
      glycogen-rich astrocytes also are seen. Reactive hypertrophic astrocytes exhibit
      increased amounts of dilated smooth and rough endoplasmic reticulum,
      microtubules, and gliofilaments. Perisynaptic astrocyte ensheathments of neuropil
      synaptic contacts are lost, and the perivascular astrocyte end-feet appear
      dissociated from the capillary basement membrane. The interastrocytary gap
      junctions appear fragmented.

PMID- 24134800
TI  - 'Did not attends' in children 0-10: a scoping review.
AB  - Patients who do not attend ('DNA') health appointments have been identified as a
      service problem incurring significant costs to the NHS. In order to explore the
      causes, effects and costs of child DNAs, we carried out a scoping study to map
      the literature and identify gaps in the research. Given the breadth of issues
      underpinning DNAs, a scoping study, including research studies, audits, policy
      documents and conference abstracts, was the most useful way to map the field. To
      foster public and patient participation, we sought advice from parents
      participating in the National Children's Bureau's Family Research Advisory Group.
      From a pool of 1997 items, we found few UK studies with non-attendance of 0-10
      year olds as a primary focus, though many more incidentally reported DNA rates.
      Overall, four topics predominated: the conceptualization of DNAs; the correlates
      of non-attendance; initiatives to reduce non-attendance; and the relationship
      between non-attendance and safeguarding. The Family Research Advisory Group
      identified broadly similar issues, but with a stronger emphasis on communication
      and practical matters. While there may be circumstances where failing to attend
      appointments makes little or no difference to a child (or even benefits them) it
      is likely that there are children whose health or well-being are compromised as a
      result of failing to attend appointments. Both 'over' and 'under'-attendance can
      be a source of anxiety to health professionals. Areas where further work is
      needed include robust evaluation of the effectiveness, cost-effectiveness and
      maintenance of measures to reduce DNAs and a better understanding of the
      relationship of safeguarding to non-attendance. 

PMID- 24134801
TI  - Atmospheric chemistry of methyl and ethyl N,N,N',N'-tetramethylphosphorodiamidate
      and O,S-dimethyl methylphosphonothioate.
AB  - Rate constants for the reactions of OH radicals with methyl N,N,N',N'
      tetramethylphosphorodiamidate [CH3OP(O)[N(CH3)2]2; MTMPDA], ethyl N,N,N',N'
      tetramethylphosphorodiamidate [C2H5OP(O)[N(CH3)2]2; ETMPDA], and O,S-dimethyl
      methylphosphonothioate [CH3OP(O)(CH3)SCH3; OSDMMP] have been measured over the
      temperature range 281-349 K at atmospheric pressure of air using a relative rate
      method. The rate expressions obtained were 4.96 * 10(-12) e((1058+/-71)/T) cm(3)
      molecule(-1) s(-1) (1.73 * 10(-10) cm(3) molecule(-1) s(-1) at 298 K) for OH +
      MTMPDA, 4.46 * 10(-12) e((1144+/-95)/T) cm(3) molecule(-1) s(-1) (2.07 * 10(-10)
      cm(3) molecule(-1) s(-1) at 298 K) for OH + ETMPDA, and 1.31 * 10(-13) e((1370+/
      229)/T) cm(3) molecule(-1) s(-1) (1.30 * 10(-11) cm(3) molecule(-1) s(-1) at 298
      K) for OH + OSDMMP. The rate constant for OH + OSDMMP was independent of O2
      content over the range 2.1-71% O2 at 296 +/- 2 K. In addition, rate constants for
      the reactions of NO3 radicals and O3 with MTMPDA, of (1.4 +/- 0.1) * 10(-12)
      cm(3) molecule(-1) s(-1) and <3.5 * 10(-19) cm(3) molecule(-1) s(-1),
      respectively, were measured at 297 +/- 2 K. Products of the OH radical- and, for
      MTMPDA, NO3 radical-initiated reactions were investigated using gas
      chromatography and in situ atmospheric pressure ionization mass spectrometry. A
      product of molecular weight 180 was observed from the OH and NO3 radical
      initiated reactions of MTMPDA, and this is attributed to
      CH3OP(O)[N(CH3)2]N(CH3)CHO. Similarly, a product of molecular weight 194 was
      observed from the OH + ETMPDA reaction and attributed to
      C2H5OP(O)[N(CH3)2]N(CH3)CHO. Possible reaction mechanisms are discussed. 

PMID- 24134802
TI  - Efficient reduction of Cr(VI) in groundwater by a hybrid electro-Pd process.
AB  - Pd-catalytic process is effective for reducing a wide range of contaminants in
      groundwater. However, limited attention is paid to Cr(VI) reduction presumably
      due to the weakly oxidizing potential of Cr(VI) under circumneutral conditions.
      In this study, a new concept of in situ reducing Cr(VI) in groundwater by a
      hybrid electro-Pd process with automatic pH adjustments is proposed and
      justified. In an undivided electrolytic cell, Cr(VI) at 5 mg/L is reduced by 95%
      within 30 min under conditions of pH 3, 1 g/L Pd/Al2O3 and 20 mA current.
      Reduction of Cr(VI) increases with decreasing pH and increasing current and
      Pd/Al2O3 dosage. Inhibition of anodic O2 is significant but decreases with drop
      of pH. Atomic H is assigned as the predominant reactive species contributing to
      Cr(VI) reduction. Although H2O2 is effective for reducing Cr(VI), its production
      on Pd surface is completed inhibited by the presence of Cr(VI). The concept is
      ultimately justified using a specially configured three-electrode column. Cr(VI)
      is effectively reduced to Cr(3+) in the locally acidic Pd zone, and Cr(3+) is
      then precipitated in the downstream neutral zone. This hybrid electro-Pd process
      could be potentially applied in the in situ remediation of Cr(VI)-contaminated
      groundwater.

PMID- 24134803
TI  - Walking speed related joint kinetic alterations in trans-tibial amputees: impact
      of hydraulic 'ankle' damping.
AB  - BACKGROUND: Passive prosthetic devices are set up to provide optimal function at
      customary walking speed and thus may function less effectively at other speeds.
      This partly explains why joint kinetic adaptations become more apparent in lower
      limb amputees when walking at speeds other than customary. The present study
      determined whether a trans-tibial prosthesis incorporating a dynamic-response
      foot that was attached to the shank via an articulating hydraulic device (hyA-F)
      lessened speed-related adaptations in joint kinetics compared to when the foot
      was attached via a rigid, non-articulating attachment (rigF). METHODS: Eight
      active unilateral trans-tibial amputees completed walking trials at their
      customary walking speed, and at speeds they deemed to be slow-comfortable and
      fast-comfortable whilst using each type of foot attachment. Moments and powers at
      the distal end of the prosthetic shank and at the intact joints of both limbs
      were compared between attachment conditions. RESULTS: There was no change in the
      amount of intact-limb ankle work across speed or attachment conditions. As speed
      level increased there was an increase on both limbs in the amount of hip and knee
      joint work done, and increases on the prosthetic side were greater when using the
      hyA-F. However, because all walking speed levels were higher when using the hyA
      F, the intact-limb ankle and combined joints work per meter travelled were
      significantly lower; particularly so at the customary speed level. This was the
      case despite the hyA-F dissipating more energy during stance. In addition, the
      amount of eccentric work done per meter travelled became increased at the
      residual knee when using the hyA-F, with increases again greatest at customary
      speed. CONCLUSIONS: Findings indicate that a trans-tibial prosthesis
      incorporating a dynamic-response foot reduced speed-related changes in
      compensatory intact-limb joint kinetics when the foot was attached via an
      articulating hydraulic device compared to rigid attachment. As differences
      between attachment conditions were greatest at customary speed, findings indicate
      a hydraulic ankle-foot device is most effectual at the speed it is set-up for.

PMID- 24134804
TI  - Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally
      accessible protein biomarkers for spinal muscular atrophy.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting
      from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs
      in preclinical research have highlighted several potential novel therapies for
      SMA, increasing the need for robust and sensitive clinical trial platforms for
      evaluating their effectiveness in human patient cohorts. Given that most clinical
      trials for SMA are likely to involve young children, there is a need for
      validated molecular biomarkers to assist with monitoring disease progression and
      establishing the effectiveness of therapies being tested. Proteomics technologies
      have recently been highlighted as a potentially powerful tool for such biomarker
      discovery. METHODS: We utilized label-free proteomics to identify individual
      proteins in pathologically-affected skeletal muscle from SMA mice that report
      directly on disease status. Quantitative fluorescent western blotting was then
      used to assess whether protein biomarkers were robustly changed in muscle, skin
      and blood from another mouse model of SMA, as well as in a small cohort of human
      SMA patient muscle biopsies. RESULTS: By comparing the protein composition of
      skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle
      proteome at a late-symptomatic time-point we identified increased expression of
      both Calreticulin and GRP75/Mortalin as robust indicators of disease progression
      in SMA mice. We report that these protein biomarkers were consistently modified
      in different mouse models of SMA, as well as across multiple skeletal muscles,
      and were also measurable in skin biopsies. Furthermore, Calreticulin and
      GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients.
      CONCLUSIONS: We conclude that label-free proteomics technology provides a
      powerful platform for biomarker identification in SMA, revealing Calreticulin and
      GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting
      on disease progression in samples of muscle and skin.

PMID- 24134805
TI  - Robotic single site hysterectomy with bilateral salpingo-oophorectomy in female
      to male transsexualism.

PMID- 24134806
TI  - Concise copper-catalyzed synthesis of tricyclic biaryl ether-linked aza
      heterocyclic ring systems.
AB  - A new method for the synthesis of tricyclic biaryl ether-linked ring systems
      incorporating seven-, eight-, and nine-membered ring amines is presented. In the
      presence of catalytic quantities of copper(I), readily accessible acyclic
      precursors undergo an intramolecular carbon-oxygen bond-forming reaction
      facilitated by a "templating" chelating nitrogen atom. The methodology displays a
      broad substrate scope, is practical, and generates rare and biologically
      interesting tricyclic heteroaromatic products that are difficult to access by
      other means. 

PMID- 24134807
TI  - A 12-year cohort study on adverse pregnancy outcomes in Eastern Townships of
      Canada: impact of endometriosis.
AB  - The aim of this study was to provide a temporal-spatial reference of adverse
      pregnancy outcomes (APO) and examine whether endometriosis promotes APO in the
      same population. Among the 31 068 women who had a pregnancy between 1997 and 2008
      in Eastern Townships of Canada, 6749 (21.7%) had APO. These APO increased
      significantly with maternal age and over time (r(2 )= 0.522, p = 0.008); and were
      dominated by preterm birth (9.3%), pregnancy-induced hypertension (8.3%)
      including gestational hypertension (6.5%), low birth weight (6.3%), gestational
      diabetes (3.4%), pregnancy loss (2.2%) including spontaneous abortion (1.5%) and
      stillbirth (0.6%), intrauterine growth restriction (2.1%) and preeclampsia
      (1.8%). Among the 31 068 pregnancies, 784 (2.5%) had endometriosis and 183
      (23.3%) had both endometriosis and APO. Endometriosis has been shown to increase
      the incidence of fetal loss (OR = 2.03; 95% CI = 1.42-2.90, p < 0.0001),
      including spontaneous abortion (OR = 1.89; 95% CI = 1.23-2.93, p = 0.005) and
      stillbirth (OR = 2.29; 95% CI = 1.24-5.22, p = 0.012). This study provides a
      temporal-spatial reference on APO, which is a valuable tool for monitoring,
      comparing and correcting. It is also the first study to highlight an impact of
      endometriosis on the incidence of spontaneous abortion and stillbirth.

PMID- 24134808
TI  - Pseudo-Sanger sequencing: massively parallel production of long and near error
      free reads using NGS technology.
AB  - BACKGROUND: Usually, next generation sequencing (NGS) technology has the property
      of ultra-high throughput but the read length is remarkably short compared to
      conventional Sanger sequencing. Paired-end NGS could computationally extend the
      read length but with a lot of practical inconvenience because of the inherent
      gaps. Now that Illumina paired-end sequencing has the ability of read both ends
      from 600 bp or even 800 bp DNA fragments, how to fill in the gaps between paired
      ends to produce accurate long reads is intriguing but challenging. RESULTS: We
      have developed a new technology, referred to as pseudo-Sanger (PS) sequencing. It
      tries to fill in the gaps between paired ends and could generate near error-free
      sequences equivalent to the conventional Sanger reads in length but with the high
      throughput of the Next Generation Sequencing. The major novelty of PS method lies
      on that the gap filling is based on local assembly of paired-end reads which have
      overlaps with at either end. Thus, we are able to fill in the gaps in repetitive
      genomic region correctly. The PS sequencing starts with short reads from NGS
      platforms, using a series of paired-end libraries of stepwise decreasing insert
      sizes. A computational method is introduced to transform these special paired-end
      reads into long and near error-free PS sequences, which correspond in length to
      those with the largest insert sizes. The PS construction has 3 advantages over
      untransformed reads: gap filling, error correction and heterozygote tolerance.
      Among the many applications of the PS construction is de novo genome assembly,
      which we tested in this study. Assembly of PS reads from a non-isogenic strain of
      Drosophila melanogaster yields an N50 contig of 190 kb, a 5 fold improvement over
      the existing de novo assembly methods and a 3 fold advantage over the assembly of
      long reads from 454 sequencing. CONCLUSIONS: Our method generated near error-free
      long reads from NGS paired-end sequencing. We demonstrated that de novo assembly
      could benefit a lot from these Sanger-like reads. Besides, the characteristic of
      the long reads could be applied to such applications as structural variations
      detection and metagenomics.

PMID- 24134809
TI  - Intraventricular tissue plasminogen activator for intraventricular hemorrhage
      caused by an arteriovenous malformation.
AB  - The use of thrombolytics delivered through an external ventricular drain has
      improved outcomes in intraventricular hemorrhage, a disease with a poor
      prognosis; however, presence of an arteriovenous malformation is generally
      considered a contraindication to thrombolytic use. Due do the high mortality with
      the current standard of care, thrombolytics should be considered as an acceptable
      treatment option despite the presence of an arteriovenous malformation in certain
      clinical situations. We review the available literature and present an additional
      patient to make the case for the use of thrombolytics for intraventricular
      hemorrhage from an arteriovenous malformation. 

PMID- 24134810
TI  - Anomalous middle turbinate with choanal obstruction and maxillary sinusitis: a
      case report.
AB  - INTRODUCTION: Although several anatomical anomalies in the middle turbinate have
      been reported, they usually remain asymptomatic. However, complicated aberrant
      middle turbinate extending through the choana to the contralateral nasopharynx
      has not been reported. CASE PRESENTATION: A 23-year-old Korean woman presented
      with a 6-month history of nasal obstruction and postnasal discharge refractory to
      medical treatment. An endoscopic examination revealed an abnormal middle
      turbinate, and a pedunculated nasal mass covered with normal mucosa that
      originated from the right lateral nasal wall filled most of the right posterior
      choana and extended to the left nasopharynx across the posterior free edge of the
      nasal septum. Computed tomography of the paranasal sinus showed abnormal bony
      trabeculation from the posterior bony attachment of the right middle turbinate to
      the left posterior nasopharyngeal wall. In addition, right maxillary sinusitis
      was observed. From these findings, the lesion was suspected to be an abnormal
      configuration of the right middle turbinate with secondary maxillary sinusitis
      and was successfully treated by resection of the malformed middle turbinate and
      middle meatal antrostomy. CONCLUSIONS: Although this case illustrates a very rare
      developmental anomaly of the middle turbinate, thorough knowledge of the
      development of and anatomical anomalies associated with the middle turbinate is
      of utmost importance to perform proper sinus surgery and avoid complications.
      Therefore, these findings should be considered by otolaryngologists, and careful
      examination of the nasal cavity is necessary to determine the existence of this
      rare anomaly.

PMID- 24134811
TI  - Use of pigs as a potential model for research into dietary modulation of the
      human gut microbiota.
AB  - The human intestinal microbial ecosystem plays an important role in maintaining
      health. A multitude of diseases including diarrhoea, gastrointestinal
      inflammatory disorders, such as necrotising enterocolitis (NEC) of neonates, and
      obesity are linked to microbial composition and metabolic activity. Therefore,
      research on possible dietary strategies influencing microbial composition and
      activity, both preventive and curative, is being accomplished. Interest has
      focused on pre- and probiotics that stimulate the intestinal production of
      beneficial bacterial metabolites such as butyrate, and beneficially affect
      microbial composition. The suitability of an animal model to study dietary linked
      diseases is of much concern. The physiological similarity between humans and pigs
      in terms of digestive and associated metabolic processes places the pig in a
      superior position over other non-primate models. Furthermore, the pig is a human
      sized omnivorous animal with comparable nutritional requirements, and shows
      similarities to the human intestinal microbial ecosystem. Also, the pig has been
      used as a model to assess microbiota-health interactions, since pigs exhibit
      similar syndromes to humans, such as NEC and partly weanling diarrhoea. In
      contrast, when using rodent models to study diet-microbiota-health interactions,
      differences between rodents and humans have to be considered. For example,
      studies with mice and human subjects assessing possible relationships between the
      composition and metabolic activity of the gut microbiota and the development of
      obesity have shown inconsistencies in results between studies. The present review
      displays the similarities and differences in intestinal microbial ecology between
      humans and pigs, scrutinising the pig as a potential animal model, with regard to
      possible health effects. 

PMID- 24134812
TI  - [Hand and occupational diseases].
AB  - Hand is frequently the site of work accidents or occupational diseases. The
      musculoskeletal upper limb is the first recognized occupational disease and
      carpal tunnel syndrome is the most common of them. The most common location of
      occupational dermatoses is the hand. Their causes are often multifactorial,
      involving chemical irritants, physical, allergens and endogenous factors (mainly
      atopic dermatitis). Occupational exposure to microtrauma and iterative use of
      vibrating tools may also be the cause of hypothenar hammer syndrome and
      acrosyndromes. The frequent chronicity and functional impairment induced by these
      attacks can cause lasting disabilities, an inability to source workstation.
      Occupational physician is a focal point for helping to maintain the position and
      the prevention of socioprofessional disinsertion. Many pathologies of the hand
      related to professional activity may benefit from a statement in occupational
      disease and thus allow the patient to obtain compensation and employment
      protection. Prevention of occupational hand diseases should be made by all health
      actors, especially in occupations and industries at risk. 

PMID- 24134813
TI  - [Assessment of liberal physician's occupational risks management on the exposure
      to biological fluids].
AB  - INTRODUCTION: During their practice, liberal physicians might have a risk of
      viral exposure to biological fluids. That risk is well-known in hospitals. The
      purpose of this study was to measure those occupational risks into their own
      private practice. METHODS: This observational descriptive transversal
      multicentral, epidemiological study is based on the information collected from
      400 physicians (general practitioners, ENT specialists, dermatologists,
      pediatricians, rheumatologists and gynecologists), working in own private
      practice in Lorraine. They received by post a confidential survey consisting of
      multiple-choice and open questions, asking for their activity, their risks of
      being exposed to biological fluids, their vaccine coverage and their potentially
      infectious medical waste (PIMW) management. RESULTS: Among 175 physicians who
      replied to the survey, 153 did invasive procedures and 58 encountered an
      accidental blood exposure (ABE). The execution of invasive procedures was the
      main factor in having an ABE (P=0.0023). Around 89.5 % of the complications were
      due to percutaneous injuries. Still 30.9 % of the physicians always recapped
      needles and 40 % hadn't a complementary health cover. More than 82 % were up-to
      date on mandatory vaccinations (hepatitis B and diphtheria-tetanus
      poliomyelitis). In private practice, 97.6 % of physicians sort out blunt objects
      (prickly or sharp), which is quite satisfactory in comparison with only 60.5 % of
      them who sort out soft wastes and 44.6 % of blunt objects at patient's home.
      CONCLUSION: Even if physician's blunt objects disposal in private practice and
      their mandatory vaccination are satisfactory, "standard" precautions, safety
      equipment use and soft wastes disposal can be improved.

PMID- 24134814
TI  - [Smoking prevention in preoperative patient factsheets].
AB  - INTRODUCTION: Information for patients undergoing elective surgery is often
      supported by factsheets. This information is required for ethical and legal
      reasons. Among the 11 million surgical procedures performed annually in France,
      three million concern smokers. Data of a 2005 French Expert's conference show
      that smoking doubles or triples the risk of postoperative complications and
      quitting smoking cancels this risk. METHODS: By a query on www.google.fr, 100
      factsheets were collected in 2009 (pilot study) and 500 in 2012. These factsheets
      were systematically analyzed on tobacco information. Issuers were contacted by
      mail, email and telephone to suggest improvements on these factsheets. A return
      to the websites where the 500 factsheets have been issued was performed 6 months
      later. RESULTS: In 2009, only 24.0% of factsheets mentioned tobacco. In 2012,
      29.4% of factsheets evoked tobacco. When tobacco is mentioned, information's were
      rarely complete. Cosmetic surgeons, maxillofacial surgeons and to a lesser extent
      orthopaedists are those who raise most often the tobacco issue. After contact
      with issuers, 41 factsheets were removed from the sites. Factsheets with tobacco
      information increased from 147/500 (29.4%) to 175/459 (38.1%) and the quality
      score of the information increased from 3.4 to 6.0. The message suggested by OFT
      was: "Smoking increases the risk of surgical complications of any surgery.
      Quitting smoking 6-8 weeks before surgery eliminates this additional risk. If you
      smoke, talk to your doctor, your surgeon and your anesthesiologist or call the
      French quitline TIS 3989 to help you to reduce the risk and put all the chances
      on your side". This sentence was included in 54 factsheets. CONCLUSION: There is
      still work to do to improve information's on smoking risk in perioperative
      factsheets. The aim is to reduce postoperative complications, costs and avoid
      court sentences against practitioner who do not inform properly on the risks of
      smoking on surgical procedures.

PMID- 24134815
TI  - [The rheumatoid hand].
AB  - Rheumatoid arthritis usually affects the hand (90%). Without treatment, joint
      damages and deformities lead to loss of the ability to grip, grasp, and pinch,
      often leaving the patient unable to perform the activities of daily living. Early
      treatment with DMARDs +/- physical therapy is the best way to control the disease
      and prevent deformity, as well as disability, which often occurs when joints get
      damaged. Two decades later dramatic advances have been made in the medical
      therapy of RA with the expanded range of effective disease-modifying
      antirheumatic drugs. When a patient with RA develops joint damages in the hand or
      wrist that are unresponsive to medical management and injections therapy,
      surgical intervention may be necessary. Optimal care involves a team approach
      among the patient involving rheumatologists, physical therapists and hand
      surgeons. Patients with RA should be closely monitored in order to detect joint
      damages necessitating physical therapist or hand surgeon consultation.

PMID- 24134816
TI  - [Hand allograft transplantation: what are the implications?].
AB  - The first hand allograft transplantation was performed in 1998 by a French
      surgeons team and has opened the era of functional allotransfers. In France, the
      authorized preliminary study included five patients who sustained traumatic
      amputation of both hands. All patients had bilateral hand allograft
      transplantation. Long-term results (follow-up ranging from 3 to 12 years)
      undoubtedly show a useful daily function, a good psychological acceptance and a
      physiological integration. Despite several obstacles as the need of
      immunosuppressive therapy for life, hand allograft transplantation is worthy of
      interest in some outstanding situations.

PMID- 24134817
TI  - Trypanosoma brucei harbours a divergent XPB helicase paralogue that is
      specialized in nucleotide excision repair and conserved among kinetoplastid
      organisms.
AB  - Conserved from yeast to humans, TFIIH is essential for RNA polymerase II
      transcription and nucleotide excision repair (NER). TFIIH consists of a core that
      includes the DNA helicase Xeroderma pigmentosum B (XPB) and a kinase subcomplex.
      Trypanosoma brucei TFIIH harbours all core complex components and is
      indispensable for RNA polymerase II transcription of spliced leader RNA genes
      (SLRNAs). Kinetoplastid organisms, however, possess two highly divergent XPB
      paralogues with only the larger being identified as a TFIIH subunit in T. brucei.
      Here we show that a knockout of the gene for the smaller paralogue, termed XPB-R
      (R for repair) resulted in viable cultured trypanosomes that grew slower than
      normal. XPB-R depletion did not affect transcription in vivo or in vitro and XPB
      R was not found to occupy the SLRNA promoter which assembles a RNA polymerase II
      transcription pre-initiation complex including TFIIH. However, XPB-R(-/-) cells
      were much less tolerant than wild-type cells to UV light- and cisplatin-induced
      DNA damage, which require NER. Since XPB-R(-/-) cells were not impaired in DNA
      base excision repair, XPB-R appears to function specifically in NER.
      Interestingly, several other protists possess highly divergent XPB paralogues
      suggesting that XPBs specialized in transcription or NER exist beyond the
      Kinetoplastida. 

PMID- 24134820
TI  - Mothers' perceptions of primary health-care providers: thematic analysis of
      responses to open-ended survey questions.
AB  - General practitioners and maternal, child and family health nurses have a central
      role in postpartum primary health care for women and their infants. Positive
      client-provider relationships are particularly important for women experiencing
      mental health problems or unsettled infant behaviour. However, little is known
      about their experiences of postnatal primary health care. The study aimed to
      describe views of postnatal primary health care among women completing a
      residential early parenting programme and to identify potential strategies to
      enhance provider-patient interactions. Participants (n=138) were women admitted
      with their infants to a private or a public early parenting service in Melbourne,
      Australia. Women completed a detailed self-report survey, including open-ended
      questions about experiences of primary health-care services, and a structured
      psychiatric interview to diagnose anxiety and depression. Survey responses were
      analysed thematically. Womens' experiences of primary health care were influenced
      by their perceptions of provider competence and the quality of interactions.
      While similar positive characteristics of doctor and nurse care were valued,
      medical and nursing practices were judged in different ways. Women described GPs
      who listened, understood and were thorough as providing good care, and maternal,
      child and family health nurses were valued for providing support, advice and
      encouragement. Threats to therapeutic relationships with doctors included feeling
      rushed during consultations, believing that GPs were not mental health-care
      providers and the clinician not being 'good' with the infant; with nurses,
      problems included feeling judged or given advice that was inconsistent or lacked
      an evidence-base. Postpartum primary health care will be improved by unhurried
      consultations, empathic recognition, encouragement, evidence-informed guidance
      and absence of criticism. 

PMID- 24134819
TI  - Characterization of a new V gene replacement in the absence of activation-induced
      cytidine deaminase and its contribution to human B-cell receptor diversity.
AB  - In B cells, B-cell receptor (BCR) immunoglobulin revision is a common route for
      modifying unwanted antibody specificities via a mechanism called VH replacement.
      This in vivo process, mostly affecting heavy-chain rearrangement, involves the
      replacement of all or part of a previously rearranged IGHV gene with another
      germline IGHV gene located upstream. Two different mechanisms of IGHV replacement
      have been reported: type 1, involving the recombination activating genes complex
      and requiring a framework region 3 internal recombination signal; and type 2,
      involving an unidentified mechanism different from that of type 1. In the case of
      light-chain loci, BCR immunoglobulin editing ensures that a second V-J
      rearrangement occurs. This helps to maintain tolerance, by generating a novel BCR
      with a new antigenic specificity. We report that human B cells can, surprisingly,
      undergo type 2 replacement associated with kappa light-chain rearrangements. The
      de novo IGKV-IGKJ products result from the partial replacement of a previously
      rearranged IGKV gene by a new germline IGKV gene, in-frame and without deletion
      or addition of nucleotides. There are wrcy/rgyw motifs at the 'IGKV donor-IGKV
      recipient chimera junction' as described for type 2 IGHV replacement, but
      activation-induced cytidine deaminase (AID) expression was not detected. This
      unusual mechanism of homologous recombination seems to be a variant of gene
      conversion-like recombination, which does not require AID. The recombination
      phenomenon described here provides new insight into immunoglobulin locus
      recombination and BCR immunoglobulin repertoire diversity. 

PMID- 24134821
TI  - Prognostic indicators in cats with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Left atrial (LA) enlargement, congestive heart failure (CHF), and
      aortic thromboembolism (ATE) are associated with decreased survival in cats with
      hypertrophic cardiomyopathy (HCM), but the prognostic value of echocardiographic
      variables has not been well characterized. HYPOTHESIS/OBJECTIVES: We hypothesized
      that LA echocardiographic variables and assessment of left ventricular (LV)
      diastolic and systolic function would have prognostic value in cats with HCM.
      ANIMALS: Two hundred eighty-two cats diagnosed with HCM. METHODS: Clinical and
      echocardiographic records of affected cats seen at the Royal Veterinary College
      from 2004 to 2009 were retrospectively analyzed. Only cats with echocardiographic
      confirmation of LV diastolic wall thickness >= 6 mm were included. Outcomes were
      obtained from clinical records or referring veterinarians and owners. RESULTS:
      Deaths occurred in 164 cats, of which 107 were believed to have been cardiac
      deaths. Univariable predictors of an increased risk of cardiac death included
      older age, absence of a murmur, presence of a gallop sound or arrhythmia,
      presentation with either CHF or ATE, extreme LV hypertrophy (>= 9.0 mm), LV
      fractional shortening (FS%) <= 30%, regional wall hypokinesis, increased left
      atrial size, decreased left atrial function, spontaneous echo-contrast/thrombus
      or both, absence of left ventricular outflow tract obstruction, and a restrictive
      diastolic filling pattern. Cox's proportional hazard analysis identified LA
      dysfunction, low LV systolic function, and extreme LV hypertrophy as independent
      predictors of decreased cardiac survival time. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Echocardiographic measurement of LA function, extreme LV hypertrophy,
      and LV systolic function provides important prognostic information in cats with
      HCM.

PMID- 24134822
TI  - Effects of parental origins and length of residency on adiposity measures and
      nutrition in urban middle school students: a cross-sectional study.
AB  - BACKGROUND: The prevalence of obesity in U.S. has been rising at an alarming
      rate, particularly among Hispanic, African, and Asian minority groups. This trend
      is due in part to excessive calorie consumption and sedentary lifestyle. We
      sought to investigate whether parental origins influence eating behaviors in
      healthy urban middle school students. METHODS: A multiethnic/racial population of
      students (N = 182) enrolled in the ROAD (Reduce Obesity and Diabetes) Study, a
      school-based trial to assess clinical, behavioral, and biochemical risk factors
      for adiposity and its co-morbidities completed questionnaires regarding parental
      origins, length of US residency, and food behaviors and preferences. The primary
      behavioral questionnaire outcome variables were nutrition knowledge, attitude,
      intention and behavior, which were then related to anthropometric measures of
      waist circumference, BMI z-scores, and percent body fat. Two-way analysis of
      variance was used to evaluate the joint effects of number of parents born in the
      U.S. and ethnicity on food preference and knowledge score. The Tukey-Kramer
      method was used to compute pairwise comparisons to determine where differences
      lie. Analysis of covariance (ANCOVA) was used to analyze the joint effects of
      number of parents born in the US and student ethnicity, along with the
      interaction term, on each adiposity measure outcome. Pearson correlation
      coefficients were used to examine the relationships between maternal and paternal
      length of residency in the US with measures of adiposity, food preference and
      food knowledge. RESULTS: African Americans had significantly higher BMI, waist
      circumference and body fat percentage compared to other racial and ethnic groups.
      Neither ethnicity/race nor parental origins had an impact on nutrition behavior.
      Mothers' length of US residency positively correlated with students' nutrition
      knowledge, but not food attitude, intention or behavior. CONCLUSIONS: Adiposity
      measures in children differ according to ethnicity and race. In contrast, food
      behaviors in this middle school sample were not influenced by parental origins.
      Longer maternal US residency benefited offspring in terms of nutrition knowledge
      only. We suggest that interventions to prevent obesity begin in early childhood.

PMID- 24134823
TI  - Kinetics of sodium release from wheat bread crumb as affected by sodium
      distribution.
AB  - As a basis for sodium reduction in bread, the kinetics of sodium release from
      wheat bread crumb during chewing was investigated by three independent methods
      using two in-mouth techniques and a model mastication simulator, respectively.
      Complete sodium extraction in-mouth was achieved after 30 s. Using coarse-grained
      NaCl in breadmaking significantly accelerated sodium release and led to enhanced
      salt taste, allowing a sodium reduction in bread by 25% while maintaining taste
      quality. This salt taste enhancement by accelerated sodium delivery can be
      explained by the increasing contrast in sodium concentration, which is known to
      determine salt taste perception. For the first time, the resulting inhomogeneous
      salt distribution in bread prepared by using coarse-grained NaCl was visualized
      by means of confocal laser scanning microscopy using a sodium-selective,
      fluorescent dye. 

PMID- 24134824
TI  - Dermal substitution in burns: invited commentary on "The roles of topical
      negative pressure in deep burn wounds treated by dermal substitution".

PMID- 24134825
TI  - Acid-base catalysis and crystal structures of a least evolved ancestral GFP-like
      protein undergoing green-to-red photoconversion.
AB  - In green-to-red photoconvertible fluorescent proteins, a three-ring chromophore
      is generated by the light-activated incorporation of a histidine residue into the
      conjugated pi-system. We have determined the pH-rate profile and high- and low-pH
      X-ray structures of a least evolved ancestor (LEA) protein constructed in the
      laboratory based on statistical sequence analysis. LEA incorporates the minimal
      number of substitutions necessary and sufficient for facile color conversion and
      exhibits a maximal photoconversion quantum yield of 0.0015 at pH 6.1. The rate
      measurements provide a bell-shaped curve, indicating that the reaction is
      controlled by the two apparent pKa values, 4.5 +/- 0.2 and 7.5 +/- 0.2, flanking
      the chromophore pKa of 6.3 +/- 0.1. These data demonstrate that the
      photoconversion rate of LEA is not proportional to the A-form of the GFP-like
      chromophore, as previously reported for Kaede-type proteins. We propose that the
      observed proton dissociation constants arise from the internal quadrupolar charge
      network consisting of Glu222, His203, Glu148, and Arg69. Increased active site
      flexibility may facilitate twisting of the chromophore upon photoexcitation,
      thereby disrupting the charge network and activating the Glu222 carboxylate for
      the abstraction of a proton from a carbon acid. Subsequently, the proton may be
      delivered to the Phe64 carbonyl by a hydrogen-bonded network involving Gln42 or
      by means of His65 side chain rotations promoted by protein breathing motions. A
      structural comparison of LEA with the nonphotoconvertible LEA-Q42A variant
      supports a role for Gln42 either in catalysis or in the coplanar preorganization
      of the green chromophore with the His65 imidazole ring. 

PMID- 24134826
TI  - The role of erythropoietin and erythropoietin receptor in malignant laryngeal
      tumors.
AB  - Erythropoietin (Epo) is a glycoprotein hormone responsible for erythropoiesis.
      Its effect is realized by binding erythropoietin receptor (EpoR) expressed on
      erythroid progenitor cells. Hypoxia is the main stimulus for the secretion of
      erythropoietin. Anemia is an independent negative prognostic factor for survival
      in patients with malignant diseases. Synthetic forms of erythropoietin are used
      in clinical oncology practice to increase the level of hemoglobin. As well as
      endogenous they can bind to EpoR. Considering the fact that most effects of
      synthetic Epo are negative, the role of endogenous Epo/EpoR has become an
      extremely important issue. The authors do not agree on most items related to the
      effects of exogenous Epo and EpoR in patients with head and neck carcinomas. We
      are investigating the expression of Epo/EpoR in the tissue of malignant laryngeal
      carcinoma. Our hypothesis is that less differentiated laryngeal carcinomas will
      have a higher level of endogenous Epo/EpoR expression. Therefore, in patients
      with positive Epo/EpoR we expect shorter survival and poorer locoregional disease
      control. We anticipate that our hypothesis may help to provide the role of
      endogenous Epo/EpoR in patients with malignant tumors of the larynx. If the
      assumptions of this study are confirmed, the patients with laryngeal carcinomas
      whose tumor cells express Epo/EpoR should not be considered for the treatment of
      anemia with recombinant erythropoietin in any case. We also point out that our
      research will expand the knowledge of the biology of laryngeal tumor cells and
      that the results could be utilized as basic knowledge in development of future
      therapeutic strategies. 

PMID- 24134827
TI  - Is amisulpride safe when prescribed to breast and prostate cancer patients?
AB  - In the last decades, the potential association between antidepressants and cancer
      risk has been increasingly investigated. Fundamental researches, performed on
      animal models and cell tumoral lines, have highlighted several biological
      mechanisms possibly supporting this association. Nevertheless, the
      epidemiological studies investigating the risk of cancer in patients receiving
      selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants
      (TCAs) have provided conflicting and inconclusive results. Therefore, the
      prescription of several antidepressants in oncologic patients still remains a
      matter of discussion. The aim of this review is to present and discuss available
      evidence concerning the association between the risk of breast and prostate
      cancer and the use of antidepressant medications. Thus, consistencies,
      differences, and contradictions of available data are reported. A special focus
      is addressed to amisulpiride, a widely prescribed drug still poorly investigated
      with regard to the risk of cancer occurrence and recurrence. Overall, there is no
      definitive evidence of increased risk of breast and prostate cancer among
      patients exposed to SSRIs and TCAs. The association between amisulpiride and
      cancer risk has been to date scarcely explored and considered in clinical
      settings. Nevertheless, the hyperprolactinemia frequently resulting from its
      adoption has been repeatedly associated, to increased cancer risk and poorer
      prognosis in cancer patients. Thus, the use of amisulpiride among cancer patients
      should be carefully considered. 

PMID- 24134828
TI  - A phenomenological investigation into the opposing effects of fluid flow on
      sonochemical activity at different frequency and power settings. 2. Fluid
      circulation at high frequencies.
AB  - Sonochemical activity is dependent on flow patterns within the reactor and either
      no affect or a decrease in activity was observed at 376, 995, and 1179 kHz from
      overhead stirring. The interaction of fluid flow with ultrasound was further
      investigated in this study with circulatory flow. The effect of fluid circulation
      on radical production was investigated at two circulation speeds, with and
      without surface stabilisation. The sonochemical activity was determined by the
      yield of hydrogen peroxide, measured by iodide dosimetry. The sonochemically
      active region was pictured using sonochemiluminescence imaging and the flow
      fields were visualised with dyed flow videos. At 376 and 995 kHz, an increase in
      sonochemical activity was observed with the slower flow rate; however at 1179
      kHz, the sonochemical activity was either not affected or decreased. The observed
      changes in sonochemical activity were attributed to an increase in asymmetry of
      the bubble collapse brought about by fluid motion.

PMID- 24134829
TI  - Propargylation of indene-1,3-dione under a new phase-transfer catalyst combined
      with ultrasonication--a kinetic study.
AB  - In the present study, kinetics of synthesis of 2,2-di(prop-2-ynyl)-1H-indene
      1,3(2H)-dione was successfully carried out by propargylation of indene-1,3-dione
      with propargyl bromide using aqueous potassium hydroxide and catalyzed by a newly
      synthesized phase-transfer catalyst viz., N-benzyl-N-ethyl-N-isopropylpropan-2
      ammonium bromide, PTC under ultrasonic (40 kHz, 300 W) assisted organic solvent
      condition. The pseudo first-order kinetic equation was applied to describe the
      overall reaction. Under ultrasound irradiation (40 kHz, 300 W) in a batch
      reactor, it shows that the overall reaction rate can be greatly enhanced with
      ultrasound irradiation than without ultrasound.

PMID- 24134830
TI  - Cross-border promotion of formula milk in Lao People's Democratic Republic.
AB  - AIM: This study aims to examine the influence of formula milk promotion via the
      media from Thailand to Lao People's Democratic Republic (PDR), where a cultural
      and linguistic proximity are shared. METHODS: A cross-sectional study was
      conducted through a structured questionnaire survey and focus group discussion
      (FGD) with mothers who had children under 2 years of age and lived in Vientiane
      Capital, Lao PDR. Multivariate logistic regression models were constructed for
      quantitative data analysis. Content analysis was used for qualitative data
      analysis. RESULTS: Among infants aged 6-23 months, exclusive breastfeeding (EBF)
      rate for 6 months was 16.1% (n = 106/658). Among infants aged 0-5 months, 17.6%
      (n = 61/346) was exclusively breastfed at the time of survey (24 h recall). Of
      1022 mothers, 89.9% reported frequent exposure to the Thai media's promotion of
      formula milk through TV commercials and 79.1% identified TV commercial as
      influential for them to develop a positive attitude towards the use of formula
      milk. In multivariate logistic regression analyses, mothers who reported a
      positive attitude towards Thai TV commercial on the formula use (n = 449) were
      approximately 75% less likely to practice EBF for 6 months than those who
      reported a negative attitude (n = 64). FGD further revealed that the participants
      tend to believe in the information in TV commercial for formula milk. CONCLUSION:
      The promotion of formula milk via media from Thailand negatively affects
      breastfeeding mothers in Lao PDR. Cross-border impacts of promoting formula milk
      should be addressed globally.

PMID- 24134831
TI  - Multiple muscle cell alterations in a case of encephalomyopathy.
AB  - Skeletal muscle from an encephalomyopathy was examined by morphological and
      biochemical modalities. Mitochondria displayed variability in size, numbers per
      myocyte, and morphology. Certain organelles had stacks of dense cristae, others
      contained variable numbers of crystalloids or several lipid droplets. In isolated
      skeletal muscle mitochondria, oxidative phosphorylation was reduced, but
      activities of the electron transport chain components were unaffected. This is
      the second case of adult onset encephalomyopathy with a phenotype overlapping
      MERRF and Kearns-Sayre syndrome associated with a heteroplasmic mtDNA 3255G > A
      mutation in the tRNA(UUR(LEU)). This study emphasizes the desirability of a
      multidisciplinary approach in the diagnosis of complex myopathies.

PMID- 24134832
TI  - The Coriell personalized medicine collaborative pharmacogenomics appraisal,
      evidence scoring and interpretation system.
AB  - Implementation of pharmacogenomics (PGx) in clinical care can lead to improved
      drug efficacy and reduced adverse drug reactions. However, there has been a lag
      in adoption of PGx tests in clinical practice. This is due in part to a paucity
      of rigorous systems for translating published clinical and scientific data into
      standardized diagnostic tests with clear therapeutic recommendations. Here we
      describe the Pharmacogenomics Appraisal, Evidence Scoring and Interpretation
      System (PhAESIS), developed as part of the Coriell Personalized Medicine
      Collaborative research study, and its application to seven commonly prescribed
      drugs. 

PMID- 24134833
TI  - Clinico-epidemiological data on non-melanoma skin cancer in Greece: 5-year
      experience (2005-2009) in a tertiary referral center.

PMID- 24134834
TI  - The complete genome sequence of EC1-UPM, a novel N4-like bacteriophage that
      infects Escherichia coli O78:K80.
AB  - BACKGROUND: Bacteriophage EC1-UPM is an N4-like bacteriophage which specifically
      infects Escherichia coli O78:K80, an avian pathogenic strain that causes
      colibacillosis in poultry. The complete genome sequence of bacteriophage EC1-UPM
      was analysed and compared with other closely related N4-like phage groups to
      assess their genetic similarities and differences. RESULTS: Bacteriophage EC1-UPM
      displays a very similar codon usage profile with its host and does not contain
      any tRNA gene. Comparative genomics analysis reveals close resemblance of
      bacteriophage EC1-UPM to three N4-like bacteriophages namely vB_EcoP_G7C, IME11
      and KBNP21 with a total of 44 protein coding genes shared at 70% identity
      threshold. The genomic region coding for the tail fiber protein was found to be
      unique in bacteriophage EC1-UPM. Further annotation of the tail fiber protein
      using HHpred, a highly sensitive homology detection tool, reveals the presence of
      protein structure homologous to various polysaccharide processing proteins in its
      C-terminus. Leveraging on the availability of multiple N4-like bacteriophage
      genome sequences, the core genes of N4-like bacteriophages were identified and
      used to perform a multilocus phylogenetic analysis which enabled the construction
      of a phylogenetic tree with higher confidence than phylogenetic trees based on
      single genes. CONCLUSION: We report for the first time the complete genome
      sequence of a N4-like bacteriophage which is lytic against avian pathogenic
      Escherichia coli O78:K80. A novel 928 amino acid residues tail fiber protein was
      identified in EC1-UPM which may be useful to further the understanding of phage
      host specificity. Multilocus phylogenetic analysis using core genes of sequenced
      N4-like phages showed that the evolutionary relationship correlated well with the
      pattern of host specificity.

PMID- 24134836
TI  - Respiratory infections in Enepa Amerindias; interpret with caution.

PMID- 24134835
TI  - Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa
      through interference with quorum sensing systems and T3SS.
AB  - BACKGROUND: Cis-2-dodecenoic acid (BDSF) is well known for its important
      functions in intraspecies signaling in Burkholderia cenocepacia. Previous work
      has also established an important role of BDSF in interspecies and inter-kingdom
      communications. It was identified that BDSF modulates virulence of Pseudomonas
      aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still
      not clear. RESULTS: We report here that BDSF mediates the cross-talk between B.
      cenocepacia and P. aeruginosa through interference with quorum sensing (QS)
      systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results
      revealed that exogenous addition of BDSF not only reduced the transcriptional
      expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and
      rhlR, but also simultaneously decreased the production of QS signals including 3
      oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently
      resulting in the down-regulation of biofilm formation and virulence factor
      production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are
      also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment
      with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and
      zebrafish infection models. CONCLUSIONS: These results depict that BDSF modulates
      virulence of P. aeruginosa through interference with QS systems and T3SS.

PMID- 24134837
TI  - A hydrophobic amino acid cluster inserted into the C-terminus of a recycling cell
      surface receptor functions as an endosomal sorting signal.
AB  - Cell surface receptors ubiquitylated after ligand stimulation are internalized
      and delivered to the lysosomal pathway for degradation. Ubiquitylated receptors
      are captured by ESCRT protein complexes that sort them to the lysosomal pathway.
      Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a component
      of endosomal sorting complexes required for transport (ESCRT)-0 that recognizes
      ubiquitin attached to receptors, indicating that it functions as a key molecule
      for ubiquitin-dependent endosomal sorting. In a previous study on interleukin
      (IL)-2 receptor beta (IL-2Rbeta) and IL-4 receptor alpha (IL-4Ralpha), which are
      constitutively internalized without ligand stimulation, we revealed that Hrs
      bound to IL-2Rbeta and IL-4Ralpha in a ubiquitin-independent manner, and
      identified a hydrophobic amino acid cluster in the cytoplasmic region of IL
      2Rbeta and IL-4Ralpha as the Hrs-interacting domain. However, a chimeric receptor
      containing the hydrophobic amino acid cluster inserted into the C-terminal of IL
      2Ralpha was not delivered to late endosomes, but recycled back to the plasma
      membrane. In the present study, we explored the functional domain related to
      endosomal sorting in IL-2Rbeta together with the hydrophobic amino acid cluster,
      and discovered the importance of an approximately 30-amino acid stretch following
      the C-terminus of the hydrophobic amino acid cluster in IL-2Rbeta. Even though
      the amino acid stretch following the hydrophobic amino acid cluster was composed
      of arbitrary amino acids, such a stretch was also permissive for the sorting
      ability, suggesting that the hydrophobic amino acid cluster functions as an
      endosomal sorting signal. These findings clarify part of the molecular mechanism
      underlying the ubiquitin-independent endosomal sorting of cytokine receptors that
      are constitutively internalized without ligand stimulation. 

PMID- 24134838
TI  - Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected
      rhesus macaques.
AB  - Trehalose 6,6'-dimycolate (TDM) is a major glycolipid of the cell wall of
      mycobacteria with remarkable adjuvant functions. To avoid detection by the host
      innate immune system, invading mycobacteria down-regulate the expression of TDM
      by utilizing host-derived glucose as a competitive substrate for their
      mycolyltransferases; however, this enzymatic reaction results in the concomitant
      biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired
      immune system. GMM-specific, CD1-restricted T cell responses have been detected
      in the peripheral blood of infected human subjects and monkeys as well as in
      secondary lymphoid organs of small animals, such as guinea pigs and human CD1
      transgenic mice. Nevertheless, it remains to be determined how tissues respond at
      the site where GMM is produced. Here we found that rhesus macaques vaccinated
      with Mycobacterium bovis bacillus Calmette-Guerin mounted a chemokine response in
      GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells.
      Indeed, the expression of interferon-gamma, but not Th2 or Th17 cytokines, was
      prominent in the GMM-injected tissue. The GMM-elicited tissue response was also
      associated with the expression of monocyte/macrophage-attracting CC chemokines,
      such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the
      up-regulated expression of granulysin and perforin. Given that GMM is produced
      primarily by pathogenic mycobacteria proliferating within the host, the Th1
      skewed tissue response to GMM may function efficiently at the site of infection. 

PMID- 24134839
TI  - Preferential binding of p53 tumor suppressor to p21 promoter sites that contain
      inverted repeats capable of forming cruciform structure.
AB  - p53 Is one of the most critical proteins involved in protecting organisms from
      malignancies and its gene is frequently mutated in these diseases. p53 Functions
      as a transcription factor and its role in the cell is mediated by sequence
      specific DNA binding. Although the genome contains many p53-binding sequences,
      the p53 protein binds only a subset of these sequences with high affinity. One
      likely mechanism of how p53 binds DNA effectively underlies its ability to
      recognize selective local DNA structure. We analyzed the possibility of cruciform
      structure formation within different regions of the p21 gene promoter. p53
      protein remarkably activates the transcription of p21 gene after genotoxic
      treatment. In silico analysis showed that p21 gene promoter contains numerous p53
      target sequences, some of which have inverted repeats capable of forming
      cruciform structures. Using chromatin immunoprecipitation, we demonstrated that
      p53 protein binds preferentially to sequences that not only contain inverted
      repeats but also have the ability to create local cruciform structures. Gel
      retardation assay also revealed strong preference of the p53 protein for response
      element in superhelical state, with cruciform structure in the DNA sequence.
      Taken together, our results suggest that p53 response element's potential for
      cruciform structure formation could be an additional determinant in p53 DNA
      binding machinery. 

PMID- 24134840
TI  - MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation
      and apoptosis in melanoma cells.
AB  - Different groups including ours have shown that curcumin induces melanoma cell
      apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1)
      in it. We observed that curcumin activated MST1-dependent apoptosis in cultured
      melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin
      induced cell apoptosis, while MST1 over-expressing increased curcumin
      sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production
      in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked
      MST1 activation to suggest that ROS might be required for MST1 activation by
      curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was
      dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited
      curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear
      translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an
      effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that
      MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation
      and apoptosis in melanoma cells. 

PMID- 24134841
TI  - Flagella proteins contribute to the production of outer membrane vesicles from
      Escherichia coli W3110.
AB  - Gram-negative bacteria, including Escherichia coli, release outer membrane
      vesicles (OMVs) that are derived from the bacterial outer membrane. OMVs
      contribute to bacterial cell-cell communications and host-microbe interactions by
      delivering components to locations outside the bacterial cell. In order to
      explore the molecular machinery involved in OMV biogenesis, the role of a major
      OMV protein was examined in the production of OMVs from E. coli W3110, which is a
      widely used standard E. coli K-12 strain. In addition to OmpC and OmpA, which are
      used as marker proteins for OMVs, an analysis of E. coli W3110 OMVs revealed that
      they also contain abundant levels of FliC, which is also known as flagellin. A
      membrane-impermeable biotin-labeling reagent did not label FliC in intact OMVs,
      but labeled FliC in sonically disrupted OMVs, suggesting that FliC is localized
      in the lumen of OMV. Compared to the parental strain expressing wild-type fliC,
      an E. coli strain with a fliC-null mutation produced reduced amounts of OMVs
      based on both protein and phosphate levels. In addition, an E. coli W3110-derived
      strain with a null-mutation in flgK, which encodes flagellar hook-associated
      protein that is essential along with FliC for flagella synthesis, also produced
      fewer OMVs than the parental strain. Taken together, these results indicate that
      the ability to form flagella, including the synthesis of flagella proteins,
      affects the production of E. coli W3110 OMVs. 

PMID- 24134842
TI  - Uhrf2 is important for DNA damage response in vascular smooth muscle cells.
AB  - Emerging evidence shows that Uhrf1 plays an important role in DNA damage response
      for maintaining genomic stability. Interestingly, Uhrf1 has a paralog Uhrf2 in
      mammals. Uhrf1 and Uhrf2 share similar domain architectures. However, the role of
      Uhrf2 in DNA damage response has not been studied yet. During the analysis of the
      expression level of Uhrf2 in different tissues, we found that Uhrf2 is highly
      expressed in aorta and aortic vascular smooth muscle cells. Thus, we studied the
      role of Uhrf2 in DNA damage response in aortic vascular smooth muscle cells.
      Using laser microirradiation, we found that like Uhrf1, Uhrf2 was recruited to
      the sites of DNA damage. We dissected the functional domains of Uhrf2 and found
      that the TTD, PHD and SRA domains are important for the relocation of Uhrf2 to
      the sites of DNA damage. Moreover, depletion of Uhrf2 suppressed DNA damage
      induced H2AX phosphorylation and DNA damage repair. Taken together, our results
      demonstrate the function of Uhrf2 in DNA damage response. 

PMID- 24134843
TI  - Inhibition of H3K18 deacetylation of Sirt7 by Myb-binding protein 1a (Mybbp1a).
AB  - Sirt7 localizes in the nucleus (enriched in the nucleolus) and is an NAD(+)
      dependent deacetylase with high selectivity for the acetylated lysine 18 of
      histone H3 (H3K18Ac). It has been reported that Sirt7 is necessary for
      maintaining the fundamental properties of the cancer cell phenotype and
      stabilizing the tumorigenicity of human cancer via deacetylation of H3K18Ac.
      However, the regulators of Sirt7 deacetylase activity are unknown. Myb-binding
      protein 1a (Mybbp1a) is reported to interact with and regulate the function of a
      number of transcription factors. In the present study, we demonstrated that
      Mybbp1a binds to Sirt7 in vitro and in vivo. Serial deletion studies indicated
      that N- and C-terminal regions of Sirt7 and C-terminal region of Mybbp1a are
      important for the binding. Furthermore, transfection experiments showed that
      Mybbp1a is capable of inhibiting the deacetylation activity of H3K18Ac by Sirt7.
      Our findings demonstrate that Mybbp1a is a novel negative regulator of Sirt7. 

PMID- 24134844
TI  - Inhibitory effects of LPA1 on cell motile activities stimulated by hydrogen
      peroxide and 2,3-dimethoxy-1,4-naphthoquinone in fibroblast 3T3 cells.
AB  - Reactive oxygen species (ROS) are known to mediate a variety of biological
      responses, including cell motility. Recently, we indicated that lysophosphatidic
      acid (LPA) receptor-3 (LPA3) increased cell motile activity stimulated by
      hydrogen peroxide. In the present study, we assessed the role of LPA1 in the cell
      motile activity mediated by ROS in mouse fibroblast 3T3 cells. 3T3 cells were
      treated with hydrogen peroxide and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) at
      concentrations of 0.1 and 1 MUM for 48 h. In cell motility assays with Cell
      Culture Inserts, the cell motile activities of 3T3 cells treated with hydrogen
      peroxide and DMNQ were significantly higher than those of untreated cells. 3T3
      cells treated with hydrogen peroxide and DMNQ showed elevated expression levels
      of the Lpar3 gene, but not the Lpar1 and Lpar2 genes. To investigate the effects
      of LPA1 on the cell motile activity induced by hydrogen peroxide and DMNQ, Lpar1
      overexpressing (3T3-a1) cells were generated from 3T3 cells and treated with
      hydrogen peroxide and DMNQ. The cell motile activities stimulated by hydrogen
      peroxide and DMNQ were markedly suppressed in 3T3-a1 cells. These results suggest
      that LPA signaling via LPA1 inhibits the cell motile activities stimulated by
      hydrogen peroxide and DMNQ in 3T3 cells.

PMID- 24134845
TI  - SPOCK1 is a novel transforming growth factor-beta target gene that regulates lung
      cancer cell epithelial-mesenchymal transition.
AB  - Lung cancer is the leading cause of cancer related death worldwide and the
      prognosis is still poor with 5-year survival of approximately 15%. Metastasis is
      the leading cause of death by cancer. Recent researches have demonstrated that
      epithelial-to-mesenchymal transition (EMT) plays a key role in the early process
      of metastasis of cancer cells. Here, we identified that SPARC/osteonectin, cwcv
      and kazal-like domains proteoglycan 1 (SPOCK1) is a novel transforming growth
      factor-beta1 (TGF-beta) target gene that regulates lung cancer cell EMT. TGF-beta
      has been reported as a major inductor of EMT. We observed that the expression of
      SPOCK1 in lung cancer tumor tissues is significantly higher than matched normal
      lung tissues. Moreover, the expression of SPOCK1 was also significantly higher in
      metastasis tumor tissues than non-metastasis tumor tissues. Levels of SPOCK1 mRNA
      were increased among patients with shorter disease-free survival times,
      indicating the potential role of SPOCK1 in lung cancer progression and
      metastasis. Silencing SPOCK1 expression with endoribonuclease-prepared small
      interfering RNA (esiRNA) in lung cells inhibits lung cancer cell growth, colony
      formation and invasion in vitro. Interestingly, ectopic expression of SPOCK1 in
      epithelial lung cancer cells induced EMT with increased expression of the
      mesenchymal marker Vimentin and decreased expression of epithelial marker E
      cadherin. We also found that the expression of SPOCK1 was increased under
      treatment of TGF-beta, indicating that SPOCK1 is a novel downstream target of TGF
      beta. Taken together, our study showed that SPOCK1 is a novel metastasis related
      biomarker in lung cancer and may be new diagnostic and therapeutic target for
      lung cancer.

PMID- 24134846
TI  - Acceleration of adipogenic differentiation via acetylation of malate
      dehydrogenase 2.
AB  - Previously, we identified proteins showing a differential acetylation pattern
      during adipogenic differentiation. Here, we examined the role of malate
      dehydrogenase 2 (MDH2) acetylation in the adipogenesis of 3T3-L1 preadipocytes.
      The acetylation level of MDH2 showed a dramatic increase during adipogenesis. The
      overexpression of wild-type MDH2 induced the significant acceleration of
      adipogenic differentiation. On the other hand, the acetylation-block mutant MDH2
      showed significantly reduced adipogenic differentiation compared to the wild
      type. MDH2 acetylation enhances its enzymatic activity and consequently
      intracellular NADPH level. These results suggest that the acetylation of MDH2 was
      affected by the cellular energy state and subsequently regulated adipogenic
      differentiation. 

PMID- 24134847
TI  - Human metastatic melanoma cell lines express high levels of growth hormone
      receptor and respond to GH treatment.
AB  - Accumulating evidence implicates the growth hormone receptor (GHR) in
      carcinogenesis. While multiple studies show evidence for expression of growth
      hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of
      quantification and only a few cancer types have been investigated. The National
      Cancer Institute's NCI60 panel includes 60 cancer cell lines from nine types of
      human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung,
      ovarian, prostate and renal. We utilized this panel to quantify expression of
      GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT
      qPCR. Both GHR and PRLR show a broad range of expression within and among most
      cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma
      than in the panel as a whole. Analysis of human metastatic melanoma biopsies
      confirmed GHR gene expression in melanoma tissue. In these human biopsies, the
      level of GHR mRNA is elevated in advanced stage IV tumor samples compared to
      stage III. Due to the novel finding of high GHR in melanoma, we examined the
      effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK
      MEL-5). GH increased proliferation in two out of three cell lines tested. Further
      analysis revealed GH-induced activation of STAT5 and mTOR in a cell line
      dependent manner. In conclusion, we have identified cell lines and cancer types
      that are ideal to study the role of GH and PRL in cancer, yet have been largely
      overlooked. Furthermore, we found that human metastatic melanoma tumors express
      GHR and cell lines possess active GHRs that can modulate multiple signaling
      pathways and alter cell proliferation. Based on this data, GH could be a new
      therapeutic target in melanoma. 

PMID- 24134848
TI  - Chondrogenic potential of stem cells derived from adipose tissue: a powerful
      pharmacological tool.
AB  - Chondrogenesis has been widely investigated in vitro using bone marrow-derived
      mesenchymal stromal cells (BM-MSCs) or primary chondrocytes. However, their use
      raises some issues partially circumvented by the availability of Adipose tissue
      derived MSCs. Herein; we characterized the chondrogenic potential of human
      Multipotent Adipose-Derived Stem (hMADS) cells, and their potential use as
      pharmacological tool. hMADS cells are able to synthesize matrix proteins
      including COMP, Aggrecan and type II Collagen. Furthermore, hMADS cells express
      BMP receptors in a similar manner to BM-MSC, and BMP6 treatment of differentiated
      cells prevents expression of the hypertrophic marker type X Collagen. We tested
      whether IL-1beta and nicotine could impact chondrocyte differentiation. As
      expected, IL-1beta induced ADAMTS-4 gene expression and modulated negatively
      chondrogenesis while these effects were reverted in the presence of the IL-1
      receptor antagonist. Nicotine, at concentrations similar to those observed in
      blood of smokers, exhibited a dose dependent increase of Aggrecan expression,
      suggesting an unexpected protective effect of the drug under these conditions.
      Therefore, hMADS cells represent a valuable tool for the analysis of in vitro
      chondrocyte differentiation and to screen for potentially interesting
      pharmacological drugs. 

PMID- 24134849
TI  - Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic
      cancer.
AB  - Pancreatic cancer is a highly lethal disease with a poor prognosis; the molecular
      mechanisms of the development of this disease have not yet been fully elucidated.
      N-myc downstream regulated gene 2 (NDRG2), one of the candidate tumor suppressor
      genes, is frequently downregulated in pancreatic cancer, but there has been
      little information regarding its expression in surgically resected pancreatic
      cancer specimens. We investigated an association between NDRG2 expression and
      prognosis in 69 primary resected pancreatic cancer specimens by
      immunohistochemistry and observed a significant association between poor
      prognosis and NDRG2-negative staining (P=0.038). Treatment with trichostatin A, a
      histone deacetylase inhibitor, predominantly up-regulated NDRG2 expression in the
      NDRG2 low-expressing cell lines (PANC-1, PCI-35, PK-45P, and AsPC-1). In
      contrast, no increased NDRG2 expression was observed after treatment with 5-aza
      2' deoxycytidine, a DNA demethylating agent, and no hypermethylation was detected
      in either pancreatic cancer cell lines or surgically resected specimens by
      methylation specific PCR. Our present results suggest that (1) NDRG2 is
      functioning as one of the candidate tumor-suppressor genes in pancreatic
      carcinogenesis, (2) epigenetic mechanisms such as histone modifications play an
      essential role in NDRG2 silencing, and (3) the expression of NDRG2 is an
      independent prognostic factor in pancreatic cancer. 

PMID- 24134850
TI  - Effect of Facebook on the life of Medical University students.
AB  - BACKGROUND: Facebook is a social networking service launched in February 2004,
      owned and operated by Facebook, Inc. As of June 2012, Facebook reports more than
      1 billion active users. Objective of study was to evaluate the effect of Facebook
      on the social life, health and behavior of medical students. METHODOLOGY: It was
      a cross sectional, observational and questionnaire based study conducted in Dow
      University OF Health Sciences during the period of January 2012 to November 2012.
      We attempted to interview all the participants who could be approached during the
      period of the study. Participants were MBBS students, while all students of other
      courses and programs were taken as exclusion criteria. Approximately 1050
      questionnaires were distributed to participants. Fifty questionnaires were
      rejected due to incomplete answers, yielding 1000 usable responses for an
      approximate 95% response rate. Informed verbal consent was taken from each
      participant. Study was ethically approved by Institutional Review Board of Dow
      University of Health Sciences. All the data was entered and analyzed through SPSS
      19. RESULT: Out of total 1000 participants, males were 400 (40%) and females were
      600 (60%). Participants were in the age group of 18-25 years with a mean age of
      20.08 years. Most of the participants were using Facebook daily (N = 640, 64%)
      for around 3-4 hours (N = 401, 40.1%). Majority of them (N = 359, 35.9%) believed
      that they were equally active on Facebook and in real life while few believed
      their social life became worse after start using Facebook (N = 372, 37.2%). Most
      of the participants admitted that they were considered as shy in real world (N =
      390, 39.0%) while in the world of Facebook they were considered as fun loving by
      their friends (N = 603, 60.3%). A large number of participants (N = 715, 75%)
      complained of mood swings. CONCLUSION: Youngsters are willing to compromise their
      health, social life, studies for the sake of fun and entertainment or whatever
      satisfaction they get after using Facebook. What we observed in our study was
      that although majority of our subjects showed multiple signs of Facebook
      addiction, they don't realize it and if even they realize it they don't want to
      quit Facebook and even if they want to quit, they can't. Our observance concluded
      that majority of the users are highly addicted.

PMID- 24134851
TI  - Curcumin protects organotypic hippocampal slice cultures from Abeta1-42-induced
      synaptic toxicity.
AB  - Increasing evidence demonstrates that beta-amyloid (Abeta) is toxic to synapses,
      resulting in the progressive dismantling of neuronal circuits. Counteract the
      synaptotoxic effects of Abeta could be particularly relevant for providing
      effective treatments for Alzheimer's disease (AD). Curcumin was recently reported
      to improve learning and memory in animal models of AD. Little is currently known
      about the specific mechanisms by which Abeta affects neuronal excitability and
      curcumin ameliorates synaptic transmission in the hippocampus. Organotypic
      hippocampal slice cultures exposed to Abeta1-42 were used to study the
      neuroprotective effects of curcumin through a spectral analysis of multi
      electrode array (MEA) recordings of spontaneous neuronal activity. Curcumin
      counteracted both deleterious effects of Abeta; the initial synaptic dysfunction
      and the later neuronal death. The analysis of MEA recordings of spontaneous
      neuronal activity showed an attenuation of signal propagation induced by Abeta
      before cell death and curcumin-induced alterations to local field potential (LFP)
      phase coherence. Curcumin-mediated attenuation of Abeta-induced synaptic
      dysfunction involved regulation of synaptic proteins, namely phospho-CaMKII and
      phospho-synapsin I. Taken together, our results expand the neuroprotective role
      of curcumin to a synaptic level. The identification of these mechanisms
      underlying the effects of curcumin may lead to new targets for future therapies
      for AD. 

PMID- 24134852
TI  - Erythrocytes and cell line-based assays to evaluate the cytoprotective activity
      of antioxidant components obtained from natural sources.
AB  - Oxidative stress can damage cellular components including DNA, proteins or
      lipids, and may cause several skin diseases. To protect from this damage and
      addressing consumer's appeal to natural products, antioxidants obtained from
      algal and vegetal extracts are being proposed as antioxidants to be incorporated
      into formulations. Thus, the development of reliable, quick and economic in vitro
      methods to study the cytoactivity of these products is a meaningful requirement.
      A combination of erythrocyte and cell line-based assays was performed on two
      extracts from Sargassum muticum, one from Ulva lactuca, and one from Castanea
      sativa. Antioxidant properties were assessed in erythrocytes by the TBARS and
      AAPH assays, and cytotoxicity and antioxidant cytoprotection were assessed in
      HaCaT and 3T3 cells by the MTT assay. The extracts showed no antioxidant activity
      on the TBARS assay, whereas their antioxidant capacity in the AAPH assay was
      demonstrated. On the cytotoxicity assays, extracts showed low toxicity, with IC50
      values higher than 200MUg/mL. C. sativa extract showed the most favourable
      antioxidant properties on the antioxidant cytoprotection assays; while S. muticum
      and U. lactuca extracts showed a slight antioxidant activity. This battery of
      methods was useful to characterise the biological antioxidant properties of these
      natural extracts. 

PMID- 24134853
TI  - Cellular and molecular mechanisms activating the cell death processes by
      chalcones: Critical structural effects.
AB  - Chalcones are naturally occurring compounds with diverse pharmacological
      activities. Chalcones derive from the common structure: 1,3-diphenylpropenone.
      The present study aims to better understand the mechanistic pathways triggering
      chalcones anticancer effects and providing evidences that minor structural
      difference could lead to important difference in mechanistic effect. We selected
      two recently investigated chalcones (A and B) and investigated them on
      glioblastoma cell lines. It was found that chalcone A induced an apoptotic
      process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also
      increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane
      potential (DeltaPsim). Chalcone B induced an autophagic cell death process (type
      II PCD), ROS-related but independent of both caspases and protein synthesis. Both
      chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen
      expressions. The present investigation reveals that despite the close structure
      of chalcones A and B, significant differences in mechanism of effect were found. 

PMID- 24134854
TI  - Non-animal photosafety assessment approaches for cosmetics based on the
      photochemical and photobiochemical properties.
AB  - The main purpose of the present study was to establish a non-animal photosafety
      assessment approach for cosmetics using in vitro photochemical and
      photobiochemical screening systems. Fifty-one cosmetics, pharmaceutics and other
      chemicals were selected as model chemicals on the basis of animal and/or clinical
      photosafety information. The model chemicals were assessed in terms of
      photochemical properties by UV/VIS spectral analysis, reactive oxygen species
      (ROS) assay and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Most
      phototoxins exhibited potent UV/VIS absorption with molar extinction coefficients
      of over 1000M(-1)cm(-1), although false-negative prediction occurred for 2
      cosmetic phototoxins owing to weak UV/VIS absorption. Among all the cosmetic
      ingredients, ca. 42% of tested chemicals were non-testable in the ROS assay
      because of low water solubility; thereby, micellar ROS (mROS) assay using a
      solubilizing surfactant was employed for follow-up screening. Upon combination
      use of ROS and mROS assays, the individual specificity was 88.2%, and the
      positive and negative predictivities were estimated to be 94.4% and 100%,
      respectively. In the 3T3 NRU PT, 3 cosmetics and 4 drugs were incorrectly
      predicted not to be phototoxic, although some of them were typical
      photoallergens. Thus, these in vitro screening systems individually provide false
      predictions; however, a systematic tiered approach using these assays could
      provide reliable photosafety assessment without any false-negatives. The combined
      use of in vitro assays might enable simple and fast non-animal photosafety
      evaluation of cosmetic ingredients. 

PMID- 24134855
TI  - The feasibility, acceptance, and key features of a prevention-focused oral health
      education program for HIV+ adults.
AB  - Poor oral health is common in HIV+ adults. We explored the feasibility,
      acceptance, and key features of a prevention-focused oral health education
      program for HIV+ adults. This was a pilot substudy of a parent study in which all
      subjects (n = 112) received a baseline periodontal disease (PD) examination and
      provider-delivered oral health messages informed by the Information-Motivation
      Behavioral Skills (IMB) Model. Forty-one parent study subjects were then eligible
      for the substudy; of these subjects, a volunteer sample was contacted and
      interviewed 3-6 months after the baseline visit. At the recall visit, subjects
      self-reported behavior changes that they had made since the baseline. PD was
      reassessed using standard clinical assessment guidelines, and results were shared
      with each subject. At recall, individualized, hands-on oral hygiene coaching was
      performed and patients provided feedback on this experience. Statistics included
      frequency distributions, means, and chi-square testing for bivariate analyses.
      Twenty-two HIV+ adults completed the study. At recall, subjects had modest, but
      nonsignificant (p > 0.05) clinician-observed improvement in PD. Each subject
      reported adopting, on average, 3.8 (+/- 1.5) specific oral health behavior
      changes at recall. By self-report, subjects attributed most behavior changes
      (95%) to baseline health messages. Behavior changes were self-reported for
      increased frequency of flossing (55%) and toothbrushing (50%), enhanced
      toothbrushing technique (50%), and improved eating habits (32%). As compared to
      smokers, nonsmokers reported being more optimistic about their oral health (p =
      0.024) at recall and were more likely to have reported changing their oral health
      behaviors (p = 0.009). All subjects self-reported increased knowledge after
      receiving hands-on oral hygiene coaching performed at the recall visit. In HIV+
      adults, IMB-informed oral health messages promoted self-reported behavior change,
      subjects preferred more interactive, hands-on coaching. We describe a holistic
      clinical behavior change approach that may provide a helpful framework when
      creating more rigorously designed IMB-informed studies on this topic.

PMID- 24134856
TI  - Food-derived serotonergic modulators: effects on mood and cognition.
AB  - The most frequently described drugs in the treatment of mood disorders are
      selective serotonin reuptake and monoamine oxidase (MAO) inhibitors, enhancing
      serotonin levels in the brain. However, side-effects have been reported for these
      drugs. Because serotonin levels in the brain are dependent on the availability of
      the food-derived precursor tryptophan, foods such as chicken, soyabeans, cereals,
      tuna, nuts and bananas may serve as an alternative to improve mood and cognition.
      Here we discuss the effects of high- or low-tryptophan-containing food, as well
      as plant extracts with a modest monoamine reuptake and MAO-A inhibition
      functional profile, on mood and cognition in healthy and vulnerable human
      subjects and rodents. Together the studies suggest that there is an inverted U
      shaped curve for plasma tryptophan levels, with low and too high tryptophan
      levels impairing cognition, and moderate to high tryptophan levels improving
      cognition. This relationship is found for both healthy and vulnerable subjects.
      Whereas this relationship may also exist for mood, the inverted U-shaped curve
      for plasma tryptophan levels and mood may be based on different tryptophan
      concentrations in healthy v. vulnerable individuals. Animal studies are emerging
      and allow further understanding of effects and the mode of action of food-derived
      serotonergic components on mood, cognition and mechanisms. Ultimately, insight
      into the concentrations of tryptophan and other serotonergic components in food
      having beneficial effects on mood and cognition in healthy, but particularly
      vulnerable, subjects may support well-being in our highly demanding society. 

PMID- 24134857
TI  - AgedCare+GP: description and evaluation of an in-house model of general practice
      in a residential aged-care facility.
AB  - This paper describes a medical model to provide in-house GP services to residents
      of aged-care facilities. Access to GP services for aged-care residents is
      decreasing, partially due to the changing demographic of the Australian GP
      workforce. The model we have developed is an in-house GP (AgedCare+GP) trialled
      in a publicly funded residential aged-care facility (RACF). The service model was
      based on the GP cooperative used in our after-hours general practice
      (AfterHours+GP). Briefly, the service model involves rostering a core group of
      GPs to provide weekly sessional clinics at the RACF. Financial contributions from
      appropriate Medicare Benefits Schedule (MBS) items for aged-care planning
      (including chronic conditions) provided adequate funds to operate the clinic for
      RACF residents. Evaluation of the service model used the number of resident
      transfers to the local emergency department as the primary outcome measure. There
      were 37 transfers of residents in the 3 months before the commencement of the
      AgedCare+GP and 11 transfers over a 3-month period at the end of the first year
      of operation; a reduction of almost 70%. This project demonstrates that
      AgedCare+GP is a successful model for GP service provision to RACF residents, and
      it also reduces the number of emergency department transfers. 

PMID- 24134858
TI  - Ultrastructural pathology of rat lung injury induced by ischemic acute kidney
      injury.
AB  - Ischemic acute kidney injury (AKI) is a common complication during inpatient
      hospitalization, and often induces acute lung injury (ALI). A lot of studies have
      concentrated on the relevance between AKI and ALI, but the underlying mechanisms
      of AKI- associated ALI have remained unclear until now. One reason is that
      evidence of the ultrastructural pathology of AKI-associated ALI has been scarce
      and needed to be accumulated. The aims of present study are to observe
      ultrastructural changes, and to reveal leukocyte trafficking of ALI induced by
      ischemic AKI in rats. For this purpose light microscopy (LM) and electron
      microscopy (EM), as well as morphometric analysis, were employed in present
      study. LM observations revealed distinct regions of collapsed alveoli, hemorrhage
      in alveoli, and interstitial edema in AKI-induced ALI. EM examinations provided
      facts that alveolar epithelial cells, including type I and type II cells, were
      necrotic, and endothelia cells undergoing apoptosis as well as interstitial cells
      undergoing necroptosis were noted in AKI lungs. In addition, shrinkage and
      decreased or disappeared lamellar bodies were evident in alveolar type II cell of
      AKI rat lungs. Leukocyte numerical density on area (NA) in AKI lungs was
      significantly more than that in sham lungs. Based on the morphological criteria
      from EM examinations and morphometric analysis, a conclusion was that necrosis,
      including necroptosis, and apoptosis were involved in damaged lung induced by
      AKI. And inflammation also contributed to acute lung injury of rats with AKI.

PMID- 24134859
TI  - Allen masters peritoneal defect: a potential pathway to deep infiltrating
      rectovaginal endometriosis?

PMID- 24134860
TI  - Analysis of epigenetic changes in survivors of preterm birth reveals the effect
      of gestational age and evidence for a long term legacy.
AB  - BACKGROUND: Preterm birth confers a high risk of adverse long term health
      outcomes for survivors, yet the underlying molecular mechanisms are unclear. We
      hypothesized that effects of preterm birth can be mediated through measurable
      epigenomic changes throughout development. We therefore used a longitudinal birth
      cohort to measure the epigenetic mark of DNA methylation at birth and 18 years
      comparing survivors of extremely preterm birth with infants born at term.
      METHODS: Using 12 extreme preterm birth cases and 12 matched, term controls, we
      extracted DNA from archived neonatal blood spots and blood collected in a similar
      way at 18 years of age. DNA methylation was measured at 347,789 autosomal
      locations throughout the genome using Infinium HM450 arrays. Representative
      methylation differences were confirmed by Sequenom MassArray EpiTYPER. RESULTS:
      At birth we found 1,555 sites with significant differences in methylation between
      term and preterm babies. At 18 years of age, these differences had largely
      resolved, suggesting that DNA methylation differences at birth are mainly driven
      by factors relating to gestational age, such as cell composition and/or maturity.
      Using matched longitudinal samples, we found evidence for an epigenetic legacy
      associated with preterm birth, identifying persistent methylation differences at
      ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18
      years uncovered a significant overlap between sites that were differentially
      methylated at birth and those that changed with age. However, we note that
      overlapping sites may either differ in the same (300/1,555) or opposite
      (431/1,555) direction during gestation and aging respectively. CONCLUSIONS: We
      present evidence for widespread methylation differences between extreme preterm
      and term infants at birth that are largely resolved by 18 years of age. These
      results are consistent with methylation changes associated with blood cell
      development, cellular composition, immune induction and age at these time points.
      Finally, we identified ten probes significantly associated with preterm
      individuals and with greater than 5% methylation discordance at birth and 18
      years that may reflect a long term epigenetic legacy of preterm birth.

PMID- 24134861
TI  - Oral magnesium supplements decrease high blood pressure (SBP>155 mmHg) in
      hypertensive subjects on anti-hypertensive medications: a targeted meta-analysis.
AB  - Previously, we examined 44 human studies involving oral magnesium (Mg)
      supplementation for hypertension (HT), sorting them according to HT status, Mg
      dose and anti-hypertensive medication usage. We found that while some studies
      reported a significant lowering of blood pressure with Mg supplementation, others
      did not. We present here our first meta-analysis of a uniform subset from this
      series of studies. Seven studies, involving 135 hypertensive subjects on anti
      hypertensive medication continuously for at least six months, with no more than a
      two-week washout and with a mean starting systolic blood pressure (SBP)>155 mmHg,
      demonstrated a mean change of -18.7 mmHg [95% CI=-14.95 to -22.45] p<0.0001 and
      an effect size test (Cohen's d)=1.19, i.e. a large and highly significant effect.
      Meta-analysis of diastolic blood pressure (DBP) for these same seven studies
      showed a mean change in DBP of -10.9 mmHg [95% CI=-8.73 to -13.1], p<0.0001, with
      an effect size test (Cohen's d)=1.19. Other studies from our original collection,
      approaching, but not meeting the >155 mmHg starting SBP values or not complying
      as regards anti-hypertensive medication usage, showed mean changes in both SBP
      and DBP with oral Mg that, while not approaching the high-responder values of the
      present study, appeared to include some high-responder subjects combined with low
      or non-responder subjects. This uniform subset of seven studies showed a strong
      effect of Mg treatment in hypertension, which is in stark contrast to results of
      three other meta-analyses. Using non-uniform sets of studies, the small effects
      reported in previous meta-analyses may reflect a blending of dissimilar studies,
      which acted to seriously underestimate the potential of Mg in hypertension in
      some (but not all) subjects. Within studies, blending of non-, moderate and
      highresponder subjects in any one study might mask strong effects of Mg treatment
      in some subjects.

PMID- 24134863
TI  - A question of balance: achieving appropriate nutrient levels in biofortified
      staple crops.
AB  - The biofortification of staple crops with vitamins is an attractive strategy to
      increase the nutritional quality of human food, particularly in areas where the
      population subsists on a cereal-based diet. Unlike other approaches,
      biofortification is sustainable and does not require anything more than a
      standard food-distribution infrastructure. The health-promoting effects of
      vitamins depend on overall intake and bioavailability, the latter influenced by
      food processing, absorption efficiency and the utilisation or retention of the
      vitamin in the body. The bioavailability of vitamins in nutritionally enriched
      foods should ideally be adjusted to achieve the dietary reference intake in a
      reasonable portion. Current vitamin biofortification programmes focus on the fat
      soluble vitamins A and E, and the water-soluble vitamins C and B9 (folate), but
      the control of dosage and bioavailability has been largely overlooked. In the
      present review, we discuss the vitamin content of nutritionally enhanced foods
      developed by conventional breeding and genetic engineering, focusing on dosage
      and bioavailability. Although the biofortification of staple crops could
      potentially address micronutrient deficiency on a global scale, further research
      is required to develop effective strategies that match the bioavailability of
      vitamins to the requirements of the human diet. 

PMID- 24134864
TI  - Characterization of the spontaneous symmetry breaking due to quenching of a one
      dimensional superconducting loop.
AB  - We study the final distribution of the winding numbers in a 1D superconducting
      ring that is quenched through its critical temperature in the absence of magnetic
      flux. The study is conducted using the stochastic time-dependent Ginzburg-Landau
      model, and the results are compared with the Kibble-Zurek mechanism (KZM). The
      assumptions of the KZM are formulated and checked as three separate propositions.
      We find characteristic lengths and characteristic times for the processes we
      study. Besides the case of uniform rings, we examined the case of rings with
      several weak links. For temperatures close to or below Tc, the Ginzburg-Landau
      coherence length xi(0)|T/Tc-1|(-1/2) does not play the role of the correlation
      length. In order to regard the winding number as a conserved quantity, it is
      necessary to allow for a short lapse of time during which unstable configurations
      decay. We found criteria for the validity of the 1D treatment. There is no lower
      bound for the final temperatures that permit 1D treatment. For moderate quenching
      times tauQ, the variance of the winding number obeys the scaling <n2>
      proportional variant tau(-1/4)Q, as predicted by the KZM in the case of mean
      field models; for tauQ ? 10(5)h/kBTc, the dependence is weaker. We also studied
      the behavior of the system when fluctuations of the gauge field are suppressed,
      and obtained that the scaling <n2> proportional variant tau(-1/4)Q is obeyed over
      a wider range.

PMID- 24134862
TI  - The mirror neuron system in post-stroke rehabilitation.
AB  - Different treatments for stroke patients have been proposed; among them the
      mirror therapy and motion imagery lead to functional recovery by providing a
      cortical reorganization. Up today the basic concepts of the current literature on
      mirror neurons and the major findings regarding the use of mirror therapy and
      motor imagery as potential tools to promote reorganization and functional
      recovery in post-stroke patients. Bibliographic research was conducted based on
      publications over the past thirteen years written in English in the databases
      Scielo, Pubmed/MEDLINE, ISI Web of Knowledge. The studies showed how the
      interaction among vision, proprioception and motor commands promotes the
      recruitment of mirror neurons, thus providing cortical reorganization and
      functional recovery of post-stroke patients. We conclude that the experimental
      advances on Mirror Neurons will bring new rational therapeutic approaches to post
      stroke rehabilitation. 

PMID- 24134865
TI  - Video-based telehealth in Australian primary health care: current use and future
      potential.
AB  - Many Australians have limited access to health-care services due to a range of
      barriers, including geographic distance and restricted mobility, which telehealth
      can potentially address. This paper reviews the current and potential use of
      video consultation in primary health care in Australia, drawing on international
      literature. There is substantial evidence of high patient satisfaction, but many
      studies have methodological limitations. Overall, evidence of effectiveness and
      cost-effectiveness is weak. There is reasonable evidence for diagnosis, home care
      and specialist consultations by GPs with patients present. Two telehealth
      initiatives using video consultation are briefly presented. Both provide evidence
      that video consultation has a valuable role to play, but does not obviate the
      need for face-to-face consultations. Video consultation challenges traditional
      professional roles, particularly those of nurses, and can improve health workers'
      skills and job satisfaction. More fundamentally, telehealth challenges the
      traditional distinction between primary and secondary care. This can be a source
      of resistance but may ultimately be one of its strengths. Appropriately targeted
      video consultation has much potential to improve the delivery of primary health
      care in Australia, particularly in rural and remote regions. 

PMID- 24134866
TI  - Developing global health technology standards: what can other industries teach
      us?
AB  - BACKGROUND: There is a lack of effective and affordable technologies to address
      health needs in the developing world. One way to address problems of innovation
      and affordability is to design global health technologies to follow agreed-upon
      standards. This Debate article argues that we can better develop standards for
      global health technologies if we learn lessons from other industries. DISCUSSION:
      The article's Background section begins by explaining why standards are needed in
      global health. For example, if global health technologies can be modularized into
      independent interfacing parts, these parts can then interact via well-defined
      standards in a "plug and play" fashion. This can avoid development of mutually
      incompatible solutions by different organizations, speed the pace of innovation,
      unlock health systems from single providers and approaches, and lower barriers to
      entry. The Background then gives a brief primer on standards and discusses
      incentives for health standards. The article's Discussion section begins with
      brief relevant cases of standards development from other industries, including
      electricity, container shipping, CD standards, Universal Serial Bus (USB), and
      the Internet. It then explores lessons from these and other industries that
      suggest how to develop standards for global health technologies. The remainder of
      the Discussion considers intellectual property and regulatory issues and
      standards-based global health business models, and ends with a checklist of
      considerations for health standards development leaders. (The associated
      Additional file discusses observations from standards development for cell phones
      and semiconductors, as well as challenges in the standards development process
      itself.) Throughout the article, point-of-care diagnostics are used as an
      illustrative example. An initiative is already underway to explore standardized
      diagnostics platforms. SUMMARY: This Debate article aims to convince the reader
      that standards can benefit global health technologies if we learn lessons from
      other industries. The article draws from historical examples and the authors'
      experiences to suggest principles, challenges, and opportunities in developing
      these standards. If implemented well, standardized platforms can lower barriers
      to entry, improve affordability, and create a vibrant ecosystem of innovative new
      global health technologies.

PMID- 24134867
TI  - Skin color is relevant to vitamin D synthesis.
AB  - BACKGROUND: Whether dark skin produces less vitamin D after UVB radiation than
      fair skin remains controversial. OBJECTIVE: To compare 25-hydroxyvitamin D [25
      (OH)-D] levels after a single UVB exposure in fair (phototype II-III) and black
      skinned (phototype VI) volunteers. METHODS: Fair-skinned volunteers (n = 20, 4
      males/16 females, mean age: 23.2 years) and black-skinned (n = 11, 6 males/5
      females, mean age: 23.8 years) received a single total body UVB exposure (0.022
      J/cm(2)). The 25-(OH)-D levels were measured on days 0, 2 and 6. RESULTS: On day
      0, all volunteers were severely vitamin D deficient. On day 2, 25-(OH)-D levels
      of fair-skinned volunteers increased significantly (median: 11.9-13.3 ng/ml, p <
      0.0001), but not in black-skinned people (median: 8.60-8.55 ng/ml, p = 0.843).
      Again, on day 6, 25-(OH)-D levels of fair-skinned volunteers increased
      significantly (median: 11.9-14.3 ng/ml, p < 0.0001), but not in black-skinned
      people (median: 8.60-9.57 ng/ml, p = 0.375). CONCLUSION: This study suggests that
      skin pigmentation negatively influences vitamin D synthesis.

PMID- 24134868
TI  - Relationship between gap-junctional conductance and conduction velocity in
      mammalian myocardium.
AB  - BACKGROUND: Gap junction resistivity, R(j), has been proposed as a key
      determinant of conduction velocity (CV). However, studies in connexin-gene
      knockout mice demonstrated significant CV slowing only with near-complete
      connexin deletion, and these findings led to the concept of a significant
      redundancy of myocardial gap junctions. We challenged this prevailing concept and
      addressed the hypothesis that there is a continuous relationship between R(j) and
      CV, each independently measured in human and guinea-pig myocardium. METHODS AND
      RESULTS: R(j) and CV were directly measured by oil-gap impedance and
      microelectrode techniques in human left ventricular myocardium from patients with
      hypertrophic cardiomyopathy and in guinea-pig atrial and ventricular myocardium
      before and during pharmacological uncoupling with 20-umol/L carbenoxolone. There
      was a continuous relationship between R(j) and CV in human and guinea-pig
      myocardium, pre- and post-carbenoxolone (r(2)=0.946; P<0.01). In guinea-pig left
      ventricle, left atrium, and right atrium, carbenoxolone increased R(j) by 28+/
      9%, 26+/-16%, and 25+/-14% and slowed CV by 17+/-3%, 23+/-8%, and 11+/-4%
      respectively (all P<0.05 versus control). As a clinically accessible measure of
      local microscopic myocardial conduction slowing in vivo in the intact human
      heart, carbenoxolone prolonged electrogram duration in the right atrium (39.7+/
      4.2 to 42.3+/-4.3 ms; P=0.01) and right ventricle (48.1+/-2.5 to 53.3+/-5.3 ms;
      P<0.01). CONCLUSIONS: There is a continuous relationship between R(j) and CV that
      is consistent between cardiac chambers and across species, indicating that
      naturally occurring variations in cellular coupling can account for variations in
      CV, and that the concept that there is massive redundancy of coupling is not
      tenable.

PMID- 24134869
TI  - Characterization of catheter-tissue contact force during epicardial
      radiofrequency ablation in an ovine model.
AB  - BACKGROUND: Contact force (CF) during radiofrequency ablation (RFA) is an
      important determinant of endocardial lesion size with limited data on epicardial
      RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium
      in an ovine model. METHODS AND RESULTS: In 12 sheep, a 7-F irrigated RFA catheter
      with CF sensor was introduced via a pericardial incision onto/in parallel with
      ventricular epicardium. RFA (30 W per 30 second duration) was applied at 5g, 10g,
      20g, 40g, and 70g: (1) over left and right ventricular myocardium with or without
      fat, (2) either directly over or adjacent to a coronary artery, or directly over
      the phrenic nerve. Force-time integral, lesion dimensions, and coronary
      artery/phrenic nerve injury were recorded. Lesion size, volume, and force-time
      integral progressively increased with higher CF (P<0.05). Steam pops occurred
      with high CF. Epicardial fat had an attenuating effect on RF penetration into
      myocardium (P<0.05); however, myocardial RF lesions could be created at sites
      with >3.5 mm epicardial fat. At sites with epicardial fat, each 10g increment in
      CF led to a 0.6 mm increase in lesion depth, whereas each 1 mm of fat reduced
      lesion depth into underlying myocardium by 0.7 mm. Extent of acute coronary
      injury with direct and indirect RFA and phrenic nerve palsy occurrence was
      proportional to CF. CONCLUSIONS: CF is a determinant of epicardial RF lesion
      size, steam pops, acute coronary artery injury, and phrenic nerve injury.
      Although epicardial fat limits lesion size, RFA with high CF can produce small
      myocardial RF lesions at sites of thick epicardial fat.

PMID- 24134870
TI  - Cellular insulin resistance disrupts hypothalamic mHypoA-POMC/GFP neuronal
      signaling pathways.
AB  - POMC neurons play a central role in the maintenance of whole-body energy
      homeostasis. This balance requires proper regulation of POMC neurons by metabolic
      hormones, such as insulin. However, the heterogeneous cellular population of the
      intact hypothalamus presents challenges for examining the molecular mechanisms
      underlying the potent anorexigenic effects of POMC neurons, and there is
      currently a complete lack of mature POMC neuronal cell models for study. To this
      end, we have generated novel, immortalized, adult-derived POMC-expressing/alpha
      MSH-secreting cell models, mHypoA-POMC/GFP lines 1-4, representing the
      fluorescence-activated cell-sorted POMC population from primary POMC-eGFP mouse
      hypothalamus. The presence of Pomc mRNA in these cell lines was confirmed, and
      alpha-MSH was detected via immunofluorescence. alpha-MSH secretion in the mHypoA
      POMC/GFP-1 was found to increase in response to 10  ng/ml ciliary neurotrophic
      factor (CNTF) or 10  nM insulin as determined by enzyme immunoassay. Further
      experiments using the mHypoA-POMC/GFP-1 cell line revealed that 10  ng/ml CNTF
      increases Pomc mRNA at 1 and 2  h after treatment, whereas insulin elicited an
      increase in Pomc mRNA level and decreases in insulin receptor (Insr (Ir)) mRNA
      level at 4  h. Furthermore, the activation of IR-mediated downstream second
      messengers was examined by western blot analysis, following the induction of
      cellular insulin resistance, which resulted in a loss of insulin-mediated
      regulation of Pomc and Ir mRNAs. The development of these immortalized neurons
      will be invaluable for the elucidation of the cellular and molecular mechanisms
      that underlie POMC neuronal function under normal and perturbed physiological
      conditions.

PMID- 24134871
TI  - Correlation of serum magnesium with cardiovascular risk factors in maintenance
      hemodialysis patients--a cross-sectional study.
AB  - BACKGROUND AND OBJECTIVES: Changes in serum magnesium (Mg) may affect some
      clinical features of patients on maintenance hemodialysis (HD). The aims of our
      study were to evaluate the correlation between serum Mg concentration and
      clinical characteristics in Chinese HD patients, and to determine whether it has
      any relevance for cardiovascular outcomes. MEASUREMENTS: 98 chronic HD patients
      were recruited, and clinical features related to cardiovascular disease (CVD)
      were measured: the correlation between Mg and these characteristics was analyzed.
      RESULTS: In patients who were hypomagnesemic, serum Mg, creatinine (Scr), albumin
      (Alb), pre-albumin (pre-Alb) levels, protein catabolic rate per normalized body
      weight (nPCR), dietary protein intake (DPI), triceps skin fold (TSF) thickness,
      mid-arm circumference (MAC), mean mid-arm circumference (MAMC), subjective global
      assessment (SGA) scores and Kt/V were lower than in hypermagnesemic patients. On
      the other hand, the incidence of intradialytic hypotension (IDH), levels of serum
      calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), C reactive
      protein (CRP), high-density lipoprotein cholesterol (HDL-c) levels, carotid
      artery plaque (CAP), and carotid intima-media thickness (CIMT) (all p<0.05,
      respectively) were higher in patients with low serum magnesium. Correlation
      analysis showed Mg to be not only positively associated with the nutritional
      status index, but also negatively correlated with other characteristics, such as
      IDH incidence, Kt/V, Ca, P, iPTH, CRP, HDL-c, CAP, CIMT (p<0.05, respectively).
      There was no significant correlation between Mg and low-density lipoprotein
      cholesterol (LDL-c), lipoprotein-a (LP-a), cholesterol (TC), serum triglycerides
      (TG), or subjective global assessment (SGA) scores (p>0.05, respectively).
      Multiple linear regression analysis showed that Mg was negatively associated with
      CIMT, a direct predictor of CVD (beta coefficient=-0.260, p=0.009). CONCLUSIONS:
      It is suggested that lower serum Mg reflects poorer nutritional status and that
      it is also associated with other risk factors for cardiovascular disease in
      hemodialysis patients, such as greater incidence of IDH, poorer HD adequacy,
      deteriorating calcium-phosphate metabolism, inflammation and CIMT.

PMID- 24134872
TI  - A new method to evaluate glenoid erosion in instable shoulder.
AB  - BACKGROUND: We aimed to establish values and parameters using multislice
      reconstruction in axial computerized tomography (CT) in order to quantify the
      erosion of the glenoid cavity in cases of shoulder instability. METHODS: We
      studied two groups using CT. Group I had normal subjects and Group II had
      patients with shoulder instability. We measured values of the vertical segment,
      the superior horizontal, medial and inferior segments, and also calculated the
      ratio of the horizontal superior and inferior segments of the glenoid cavity in
      both normal subjects and those with shoulder instability. These variables were
      recorded during arthroscopy for cases with shoulder instability. RESULTS: The
      mean values were 40.87 mm, 17.86 mm, 26.50 mm, 22.86 mm and 0.79 for vertical
      segment, the superior horizontal, medial and inferior segments, and the ratio
      between horizontal superior and inferior segments of the glenoid cavity
      respectively, in normal subjects. For subjects with unstable shoulders the mean
      values were 37.33 mm, 20.83 mm, 23.07 mm and 0.91 respectively. Arthroscopic
      measurements yielded an inferior segment value of 24.48 mm with a loss of 2.39 mm
      (17.57%). The ratio between the superior and inferior segments of the glenoid
      cavity was 0.79. This value can be used as a normative value for evaluating
      degree of erosion of the anterior border of the glenoid cavity. However, values
      found using CT should not be used on a comparative basis with values found during
      arthroscopy. CONCLUSIONS: Computerized tomographic measurements of the glenoid
      cavity yielded reliable values consistent with those in the literature.

PMID- 24134873
TI  - The effects of dietary nitrate on blood pressure and endothelial function: a
      review of human intervention studies.
AB  - Evidence has accumulated in recent years that suggests that nitrate from the
      diet, particularly vegetables, is capable of producing bioactive NO in the
      vasculature, following bioconversion to nitrite by oral bacteria. The aim of the
      present review was to consider the current body of evidence for potential
      beneficial effects of dietary nitrate on blood pressure and endothelial function,
      with emphasis on evidence from acute and chronic human intervention studies. The
      studies to date suggest that dietary nitrate acutely lowers blood pressure in
      healthy humans. An inverse relationship was seen between dose of nitrate consumed
      and corresponding systolic blood pressure reduction, with doses of nitrate as low
      as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the
      current studies provide some promising evidence on the beneficial effects of
      dietary nitrate on endothelial function. In vitro studies suggest a number of
      potential mechanisms by which dietary nitrate and its sequential reduction to NO
      may reduce blood pressure and improve endothelial function, such as: acting as a
      substrate for endothelial NO synthase; increasing vasodilation; inhibiting
      mitochondrial reactive oxygen species production and platelet aggregation. In
      conclusion, the evidence for beneficial effects of dietary nitrate on blood
      pressure and endothelial function is promising. Further long-term randomised
      controlled human intervention studies assessing the potential effects of dietary
      nitrate on blood pressure and endothelial function are needed, particularly in
      individuals with hypertension and at risk of CVD. 

PMID- 24134874
TI  - Adult ADHD Among NSW Prisoners: Prevalence and Psychiatric Comorbidity.
AB  - OBJECTIVE: Given the paucity of research among prisoners, this study aimed to
      examine the prevalence and psychiatric comorbidity associated with adult ADHD.
      METHOD: The study was conducted at four NSW correctional facilities (2 male; 2
      female). RESULTS: Thirty-five percent of the sample screened positive for adult
      ADHD, and 17% of the sample met criteria for a full diagnosis. After adjustment,
      benzodiazepine dependence, borderline personality disorder, social phobia,
      antisocial personality disorder, and a number of lifetime psychological disorders
      remained significantly and independently associated with the diagnosis of adult
      ADHD. Lowering the threshold on the ADHD Self-Rating Scale to >=3 (vs. >=4)
      increased the sensitivity (80%-93%), but lowered the specificity (55%-47%).
      CONCLUSION: Adult ADHD among NSW prisoners is elevated, with substance use
      disorders and psychiatric comorbidity common. A greater acceptance of this
      disorder among prisoners, and appropriate treatment, is warranted.

PMID- 24134875
TI  - Neuropsychological Functioning in Adults With ADHD and Adults With Other
      Psychiatric Disorders.
AB  - OBJECTIVE: The aim was to investigate how well neuropsychological measures can
      discriminate between adults with ADHD and those with other psychiatric disorders.
      METHOD: Adults with ADHD and a clinical control group ( n = 110) were included.
      Neuropsychological functioning was investigated using measures of inhibition,
      working memory, set shifting, planning, fluency, reaction-time variability, and
      delay aversion. RESULTS: Adults with ADHD performed more poorly compared with
      clinical controls with regard to all constructs. The effects of verbal memory,
      inhibition, set shifting, fluency, and delay aversion remained significant when
      controlling for IQ. However, when controlling for basic cognitive functions, only
      the effects of inhibition, fluency, and delay aversion were significant.
      Sensitivity ranged between 64% and 75%, and specificity between 66% and 81%.
      CONCLUSION: Neuropsychological tests have a relatively poor ability to
      discriminate between adults with ADHD and clinical controls, but they may be used
      to identify individuals at particularly high risk for poor daily functioning.

PMID- 24134876
TI  - e-Learning competency for practice nurses: an evaluation report.
AB  - Practice nurses in Australia are now funded to facilitate chronic condition
      management, including self-management support. Chronic disease management
      requires an established rapport, support and proactivity between general
      practitioners, patients and the practice nurses. To achieve this, training in
      shared decision making is needed. e-Learning supports delivery and achievement of
      such policy outcomes, service improvements and skill development. However, e
      learning effectiveness for health care professionals' is determined by several
      organisational, economic, pedagogical and individual factors, with positive e
      learning experience linked closely to various supports. This paper reinforces
      previous studies showing nurses' expanding role across general practice teams and
      reports on some of the challenges of e-learning. Merely providing practice nurses
      with necessary information via web-based learning systems does not ensure
      successful learning or progress toward improving health outcomes for patients. 

PMID- 24134877
TI  - Vortex polarization dynamics in a square magnetic nanodot.
AB  - Langevin simulations at finite temperature of two-dimensional magnetic nanodots
      were performed using the Landau-Lifshitz equation with exchange and dipolar
      interactions. In a wide range of temperatures, the dynamics of square samples
      with one central vortex was studied, focusing on the out-of-plane magnetic
      component at the vortex-core. This vortex-core undergoes polarization sign
      reversals in a thermally activated process. In the intervals between polarization
      flips, the out-of-plane spin components at the vortex-core show oscillations with
      identifiable frequencies connected with certain eigenfrequencies of the system
      associated with polarity active modes. The vortex-core positions were also
      monitored. 

PMID- 24134878
TI  - Enhanced conformational sampling of carbohydrates by Hamiltonian replica-exchange
      simulation.
AB  - Knowledge of the structure and conformational flexibility of carbohydrates in an
      aqueous solvent is important to improving our understanding of how carbohydrates
      function in biological systems. In this study, we extend a variant of the
      Hamiltonian replica-exchange molecular dynamics (MD) simulation to improve the
      conformational sampling of saccharides in an explicit solvent. During the
      simulations, a biasing potential along the glycosidic-dihedral linkage between
      the saccharide monomer units in an oligomer is applied at various levels along
      the replica runs to enable effective transitions between various conformations.
      One reference replica runs under the control of the original force field. The
      method was tested on disaccharide structures and further validated on
      biologically relevant blood group B, Lewis X and Lewis A trisaccharides. The
      biasing potential-based replica-exchange molecular dynamics (BP-REMD) method
      provided a significantly improved sampling of relevant conformational states
      compared with standard continuous MD simulations, with modest computational
      costs. Thus, the proposed BP-REMD approach adds a new dimension to existing
      carbohydrate conformational sampling approaches by enhancing conformational
      sampling in the presence of solvent molecules explicitly at relatively low
      computational cost. 

PMID- 24134879
TI  - Defining the structural origin of the substrate sequence independence of O
      GlcNAcase using a combination of molecular docking and dynamics simulation.
AB  - Protein glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a post
      translational modification of serine/threonine residues in nucleocytoplasmic
      proteins. O-GlcNAc has been shown to play a role in many different cellular
      processes and O-GlcNAcylation is often found at sites that are also known to be
      phosphorylated. Unlike phosphorylation, O-GlcNAc levels are regulated by only two
      enzymes, O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA).
      So far, no obvious consensus sequence has been found for sites of O
      GlcNAcylation. Additionally, O-GlcNAcase recognizes and cleaves all O
      GlcNAcylated proteins, independent of their sequence. In this work, we generate
      and analyze five models of O-GlcNAcylated peptides in complex with a bacterial
      OGA. Each of the five glycopeptides bind to OGA in a similar fashion, with OGA
      peptide interactions primarily, but not exclusively, involving the peptide
      backbone atoms, thus explaining the lack of sensitivity to peptide sequence.
      Nonetheless, differences in peptide sequences, particularly at the -1 to -4
      positions, lead to variations in predicted affinity, consistent with observed
      experimental variations in enzyme kinetics. The potential exists, therefore, to
      employ the present analysis to guide the development glycopeptide-specific
      inhibitors, or conversely, the conversion of OGA into a reagent that could target
      specific O-GlcNAcylated peptide sequences. 

PMID- 24134880
TI  - Characterization of the meningococcal serogroup X capsule N-acetylglucosamine-1
      phosphotransferase.
AB  - Neisseria meningitidis serogroups A, B, C, Y, W135 and X are responsible for most
      cases of meningococcal meningitis. Neisseria meningitidis serogroup X has
      recently emerged as a contributor to outbreaks of disease in Africa, but there is
      currently no vaccine against serogroup X. Understanding of the biosynthesis of
      the serogroup X capsular polysaccharide would provide useful tools for vaccine
      production. The serogroup X polysaccharide is a homopolymer of (alpha1->4)-linked
      N-acetylglucosamine (GlcNAc)-1-phosphate. It has been shown that the gene cluster
      xcbABC encodes synthesis of this polysaccharide. The xcbA gene product has
      significant homology with sacB, which is responsible for synthesis of the
      Neisseria serogroup A capsular polysaccharide, an (alpha1->6)-N-acetylmannosamine
      1-phosphate homopolymer. The xcbA protein also shares homology with the catalytic
      domain of human N-acetylglucosamine-1-phosphoryltransferase, a key enzyme in the
      mannose-6-phosphate receptor pathway. In this study, we show that xcbA in the
      appropriate background is sufficient for the synthesis of N. meningitidis
      serogroup X polysaccharide. By ELISA we detected polysaccharide in fractions of
      Escherichia coli expressing the xcbA gene. We isolated polysaccharide from an E.
      coli strain expressing XcbA and demonstrated that this polysaccharide has a (13)C
      NMR spectrum identical to that of polysaccharide isolated from N. meningitidis
      Group X. We also demonstrate that the purified XcbA protein is an N
      acetylglucosamine-1-phosphotransferase that transfers N-acetylglucosamine-1
      phosphate from UDP-GlcNAc to the 4-hydroxyl of an N-acetylglucosamine-1-phosphate
      oligosaccharide. Oligosaccharides fluorescently labeled at the aglycon are
      extended by XcbA only after the 4-phosphate occupying the non-reducing GlcNAc has
      been removed. The minimum size of fluorescent acceptors is a trisaccharide. 

PMID- 24134881
TI  - Differential sensitivity to the acute and sensitizing behavioral effects of
      methylphenidate as a function of strain in adolescent and young adult rats.
AB  - BACKGROUND: Behavioral effects of stimulant drugs are influenced by non
      pharmacological factors, including genetic variability and age. We examined acute
      and sensitized locomotor effects of methylphenidate in adolescent and early adult
      male Sprague Dawley (SD), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY)
      rats using a drug regimen that differentiates clearly between initial and
      enduring differences in drug responsiveness. We probed for strain and age
      differences in the sensitizing effects of methylphenidate using a cocaine
      challenge. Methylphenidate was administered to the rats in a non-home
      environment. FINDINGS: Strain differences in sensitivity to single
      methylphenidate injections depend on age and change with continuing drug
      pretreatment. While SHR rats are more sensitive to methylphenidate relative to
      WKY regardless of age and pretreatment day, SHR rats become more sensitive to
      methylphenidate than SD rats towards the end of pretreatment during early
      adulthood. SD rats exhibit greater sensitivity to methylphenidate relative to the
      WKY group during adolescence, an effect that dissipates with continued drug
      pretreatment during adulthood. Remarkably, only SHR rats, regardless of age,
      exhibit methylphenidate-induced cross-sensitization to the behavioral effects of
      cocaine. CONCLUSIONS: Our findings suggest that SHR rats are more vulnerable than
      other strains to methylphenidate-induced cross-sensitization to cocaine, at least
      when methylphenidate is administered in a non-home environment. Given that SHR
      rats are typically used to model features of attention deficit hyperactivity
      disorder, these findings may have important implications for the treatment of
      this disorder with methylphenidate.

PMID- 24134882
TI  - Salivary mineral composition in patients with oral cancer.
AB  - AIM: To analyse the mineral content of saliva in patients with oral cancer in
      order to identify possible markers that might aid the diagnosis of oral cancer.
      SUBJECTS AND METHODS: The study group consisted of 34 patients, aged 35-72 years
      with a diagnosis of oral cancer, including seven women and 27 men, before the
      start of treatment. Samples of unstimulated saliva were collected in plastic
      containers. The concentrations of sodium and potassium were assessed using ion
      selective electrodes, and the concentrations of calcium, magnesium, iron and
      phosphorus were assessed using colorimetric methods. RESULTS: Statistically
      significant differences between the study and control groups were found only for
      the concentration of sodium--higher concentrations were found in the study group.
      When comparing different cancer localisations, the highest levels of salivary
      sodium were found in cases of cancer of the floor of the oral cavity, and the
      lowest levels in tongue or parotid gland cancer. The highest calcium levels were
      found in cancer of the floor of the oral cavity, and the lowest levels in tongue
      cancer. The highest levels of magnesium were found in cancer of the floor of the
      oral cavity, and the lowest in tongue cancer. As regards the different
      histological types, higher sodium and calcium levels were found in squamous cell
      carcinomas than in other types. CONCLUSION: Salivary mineral content in patients
      with oral squamous cell carcinoma is indicative of oral dehydration; however, we
      found no evidence of any salivary mineral markers that would be useful for the
      diagnosis of oral cancer.

PMID- 24134883
TI  - Expression of INHbetaA and INHbetaB proteins in porcine oocytes cultured in vitro
      is dependent on the follicle size.
AB  - The current study aimed to investigate differential expression of inhibin betaA
      (INHbetaA) and inhibin betaB (INHbetaB) in porcine oocytes before or after in
      vitro maturation (IVM) isolated from follicles of various sizes. Porcine oocytes
      isolated from large, medium and small follicles (40 from each) were used to study
      the INHbetaA and INHbetaB protein expression pattern using western blot analysis
      before or after 44 h of oocyte IVM. An increased expression of INHbetaA was found
      in oocytes collected from large and medium follicles compared with small
      follicles before or after IVM (P < 0.001, P < 0.05, respectively). Similarly,
      higher INHbetaB levels were observed in oocytes recovered from large follicles
      compared with small (P < 0.01). As INHbetaA and INHbetaB are expressed in both
      porcine follicular somatic cells and oocytes, it can be assumed that these
      transforming growth factor beta (TGFbeta) superfamily factors are involved in the
      regulation of molecular bi-directional pathways during follicle and oocyte
      development, and can be recognized as markers of follicle and oocyte maturation.
      Moreover, the current study clearly demonstrated that inhibin expression is
      substantially associated with porcine follicle growth and development. 

PMID- 24134884
TI  - Purification and characterization of novel microtubule-associated proteins from
      Arabidopsis cell suspension cultures.
AB  - Plant microtubules (MTs) play essential roles in cell division, anisotropic cell
      expansion, and overall organ morphology. Microtubule-associated proteins (MAPs)
      bind to MTs and regulate their dynamics, stability, and organization. Identifying
      the full set of MAPs in plants would greatly enhance our understanding of how
      diverse MT arrays are formed and function; however, few proteomics studies have
      characterized plant MAPs. Using liquid chromatography-tandem mass spectrometry,
      we identified hundreds of proteins from MAP-enriched preparations derived from
      cell suspension cultures of Arabidopsis (Arabidopsis thaliana). Previously
      reported MAPs, MT regulators, kinesins, dynamins, peroxisome-resident enzymes,
      and proteins implicated in replication, transcription, and translation were
      highly enriched. Dozens of proteins of unknown function were identified, among
      which 12 were tagged with green fluorescent protein (GFP) and examined for their
      ability to colocalize with MTs when transiently expressed in plant cells. Six
      proteins did indeed colocalize with cortical MTs in planta. We further
      characterized one of these MAPs, designated as BASIC PROLINE-RICH PROTEIN1
      (BPP1), which belongs to a seven-member family in Arabidopsis. BPP1-GFP decorated
      interphase and mitotic MT arrays in transgenic Arabidopsis plants. A highly
      basic, conserved region was responsible for the in vivo MT association.
      Overexpression of BPP1-GFP stabilized MTs, caused right-handed helical growth in
      rapidly elongating tissues, promoted the formation of transverse MT arrays, and
      resulted in the outgrowth of epidermal cells in light-grown hypocotyls. Our high
      quality proteome database of Arabidopsis MAP-enriched preparations is a useful
      resource for identifying novel MT regulators and evaluating potential MT
      associations of proteins known to have other cellular functions. 

PMID- 24134885
TI  - The CALMODULIN-BINDING PROTEIN60 family includes both negative and positive
      regulators of plant immunity.
AB  - Two members of the eight-member CALMODULIN-BINDING PROTEIN60 (CBP60) gene family,
      CBP60g and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT1 (SARD1), encode positive
      regulators of plant immunity that promote the production of salicylic acid (SA)
      and affect the expression of SA-dependent and SA-independent defense genes. Here,
      we investigated the other six family members in Arabidopsis (Arabidopsis
      thaliana). Only cbp60a mutations affected growth of the bacterial pathogen
      Pseudomonas syringae pv maculicola ES4326. In contrast to cbp60g and sard1
      mutations, cbp60a mutations reduced pathogen growth, indicating that CBP60a is a
      negative regulator of immunity. Bacterial growth was increased by cbp60g only in
      the presence of CBP60a, while the increase in growth due to sard1 was independent
      of CBP60a, suggesting that the primary function of CBP60g may be to counter the
      repressive effect of CBP60a. In the absence of pathogen, levels of SA as well as
      of several SA-dependent and SA-independent pathogen-inducible genes were higher
      in cbp60a plants than in the wild type, suggesting that the enhanced resistance
      of cbp60a plants may result from the activation of immune responses prior to
      pathogen attack. CBP60a bound calmodulin, and the calmodulin-binding domain was
      defined at the C-terminal end of the protein. Transgenes encoding mutant versions
      of CBP60a lacking the ability to bind calmodulin failed to complement null cbp60a
      mutations, indicating that calmodulin-binding ability is required for the
      immunity-repressing function of CBP60a. Regulation at the CBP60 node involves
      negative regulation by CBP60a as well as positive regulation by CBP60g and SARD1,
      providing multiple levels of control over the activation of immune responses. 

PMID- 24134886
TI  - The Tomato 14-3-3 protein TFT4 modulates H+ efflux, basipetal auxin transport,
      and the PKS5-J3 pathway in the root growth response to alkaline stress.
AB  - Alkaline stress is a common environmental stress, in particular in salinized
      soils. Plant roots respond to a variety of soil stresses by regulating their
      growth, but the nature of the regulatory pathways engaged in the alkaline stress
      response (ASR) is not yet understood. Previous studies show that PIN-FORMED2, an
      auxin (indole-3-acetic acid [IAA]) efflux transporter, PKS5, a protein kinase,
      and DNAJ HOMOLOG3 (J3), a chaperone, play key roles in root H(+) secretion by
      regulating plasma membrane (PM) H(+)-ATPases directly or by targeting 14-3-3
      proteins. Here, we investigated the expression of all 14-3-3 gene family members
      (TOMATO 14-3-3 PROTEIN1 [TFT1]-TFT12) in tomato (Solanum lycopersicum) under ASR,
      showing the involvement of four of them, TFT1, TFT4, TFT6, and TFT7. When these
      genes were separately introduced into Arabidopsis (Arabidopsis thaliana) and
      overexpressed, only the growth of TFT4 overexpressors was significantly enhanced
      when compared with the wild type under stress. H(+) efflux and the activity of PM
      H(+)-ATPase were significantly enhanced in the root tips of TFT4 overexpressors.
      Microarray analysis and pharmacological examination of the overexpressor and
      mutant plants revealed that overexpression of TFT4 maintains primary root
      elongation by modulating PM H(+)-ATPase-mediated H(+) efflux and basipetal IAA
      transport in root tips under alkaline stress. TFT4 further plays important roles
      in the PKS5-J3 signaling pathway. Our study demonstrates that TFT4 acts as a
      regulator in the integration of H(+) efflux, basipetal IAA transport, and the
      PKS5-J3 pathway in the ASR of roots and coordinates root apex responses to
      alkaline stress for the maintenance of primary root elongation. 

PMID- 24134887
TI  - Rapid ammonia gas transport accounts for futile transmembrane cycling under
      NH3/NH4+ toxicity in plant roots.
AB  - Futile transmembrane NH3/NH4(+) cycling in plant root cells, characterized by
      extremely rapid fluxes and high efflux to influx ratios, has been successfully
      linked to NH3/NH4(+) toxicity. Surprisingly, the fundamental question of which
      species of the conjugate pair (NH3 or NH4(+)) participates in such fluxes is
      unresolved. Using flux analyses with the short-lived radioisotope (13)N and
      electrophysiological, respiratory, and histochemical measurements, we show that
      futile cycling in roots of barley (Hordeum vulgare) seedlings is predominately of
      the gaseous NH3 species, rather than the NH4(+) ion. Influx of
      (13)NH3/(13)NH4(+), which exceeded 200 umol g(-1) h(-1), was not commensurate
      with membrane depolarization or increases in root respiration, suggesting
      electroneutral NH3 transport. Influx followed Michaelis-Menten kinetics for NH3
      (but not NH4(+)), as a function of external concentration (Km = 152 um, Vmax =
      205 umol g(-1) h(-1)). Efflux of (13)NH3/(13)NH4(+) responded with a nearly
      identical Km. Pharmacological characterization of influx and efflux suggests
      mediation by aquaporins. Our study fundamentally revises the futile-cycling model
      by demonstrating that NH3 is the major permeating species across both plasmalemma
      and tonoplast of root cells under toxicity conditions. 

PMID- 24134888
TI  - Characterization of induced struvite formation from source-separated urine using
      seawater and brine as magnesium sources.
AB  - Struvite (MgNH4PO4.6H2O) precipitation is widely used for nutrient recovery from
      source-separated urine in view of limited natural resources. Spontaneous struvite
      formation depletes the magnesium in hydrolyzed urine so that additional magnesium
      source is required to produce induced struvite for P-recovery. The present study
      investigated the morphology and purity of induced struvite crystals obtained from
      hydrolyzed urine by using seawater and desalination brine as low cost magnesium
      sources. The results demonstrated that both seawater and brine were effective
      magnesium sources to recover phosphorus from hydrolyzed urine. Crystals obtained
      from synthetic and real urine were revealed that the morphology was feather and
      coffin shape, respectively. Structural characterization of the precipitates
      confirmed that crystallized struvite was the main product. However, co
      precipitates magnesium calcite and calcite were observed when seawater was added
      into synthetic and real urine, respectively. It was found that the presence of
      calcium in the magnesium sources could compromise struvite purity. Higher
      struvite purity could be obtained with higher Mg/Ca ratio in the magnesium
      source. Comparative analysis indicated that seawater and brine had similar effect
      on the crystallized struvite purity. 

PMID- 24134889
TI  - An investigation into the relationship between the major chemical components of
      particulate matter in urban air.
AB  - Particulate matter (PM) generally comprises such chemical components as inorganic
      ions, organic carbon (OC), elemental carbon (EC), and metals. In terms of
      environmental studies, these major chemical components of particulate matter
      (MCP) are important in understanding PM distribution, behaviors and source
      apportionment. In this study, the MCP fractions of total suspended particles
      (TSP) were measured at an urban residential area in Seoul, Korea from February to
      December in 2009. The behavior of each individual MCP was studied in order to
      explain their relationship to environmental conditions and sources. The MCP
      measured during this study period was able to account between 54% (spring) to 67%
      (fall) of total TSP composition. During the study period, it was found that the
      TSP sampled comprised mostly: anions, OC, cations, EC, and metals in decreasing
      order of abundance. Although such relative ordering seems to remain fairly
      constant over time, the relative balance of this relationship may be altered by
      variations in environmental conditions.

PMID- 24134890
TI  - Effect of salinity on extracellular polymeric substances of activated sludge from
      an anoxic-aerobic sequencing batch reactor.
AB  - The effect of salinity on extracellular polymeric substances (EPS) of activated
      sludge was investigated in an anoxic-aerobic sequencing batch reactor (SBR). The
      contents of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) were
      positively correlated with the salinity. The polysaccharide (PS) and protein (PN)
      contents in both LB-EPS and TB-EPS increased with the increase of salinity. With
      the increase of salinity from 0.5% to 6%, the PN/PS ratios in LB-EPS and TB-EPS
      decreased from 4.8 to 0.9 and from 2.9 to 1.4, respectively. The four
      fluorescence peaks in both LB-EPS and TB-EPS identified by three-dimensional
      excitation-emission matrix fluorescence spectroscopy are attributed to PN-like
      substances and humic acid-like substances. The Fourier transform infrared spectra
      of the LB-EPS and TB-EPS appeared to be very similar, but the differences across
      the spectra were apparent in terms of the relative intensity of some bands with
      the increase of salinity. The sludge volume index showed a linear correlation
      with LB-EPS (R(2)=0.9479) and TB-EPS (R(2)=0.9355) at different salinities,
      respectively. 

PMID- 24134891
TI  - Detection, fate and transport of estrogen family hormones in soil.
AB  - Estrone (E1), 17beta-estradiol (E2), and estrone-sulfate (E1-3S) are released
      into the environment in significant amounts. They are known to adversely affect
      the endocrine systems of aquatic organisms. Although previous studies clearly
      demonstrate that free hormones sorb strongly to soil and degrade quickly,
      significant amounts of free and the more persistent conjugated estrogens can be
      still detected in various environmental media. To date, E1-3S has been considered
      as a metabolite that forms either during the animal hormone cycle or as a
      degradation product of precursor hormones like E2-3S. We performed small-scale
      laboratory column tests to investigate two major features: transport and
      degradation of E2, and formation of E1-3S and E1. To evaluate the influence of
      soil microbial activity, one portion of soil was autoclaved and the background
      solution treated with sodium azide. The results demonstrate that (i) E2 is
      degraded to E1 and E1-3S in non-autoclaved soil, and to E1 in autoclaved soil,
      (ii) the formation of E1-3S is biologically driven, and (iii) the transformation
      of E2 to E1 does not require biological interaction. An inverse modeling approach
      was used to quantify the transport parameters and degradation rate coefficients.

PMID- 24134892
TI  - Avermectin induced inflammation damage in king pigeon brain.
AB  - To determine the effect of Avermectin (AVM) on inflammation damage in king pigeon
      brain, eighty two-month-old American king pigeons were randomly divided into four
      groups, and were fed with either commercial diet or AVM-supplemented diet
      containing 20 mg kg(-1)diet, 40 mg kg(-1)diet, and 60 mg kg(-1)diet AVM for 30,
      60 and 90 d, respectively. Then, the expression level of inflammatory factors
      (iNOS, PTGEs, NF-kappaB), histological damage, and ultra-structural damage were
      examined. It showed that AVM caused higher expressions (P<0.05) of iNOS, PTGEs,
      NF-kappaB with disorganized histological and ultra-structural structures in
      cerebrum, cerebellum, and optic lobe. Meanwhile, inflammatory and
      histopathological damage were induced by AVM in king pigeon brains. In addition,
      the main targeted organelle in nervous system was mitochondria, which indicated
      that mitochondria may be relevant to the process of inflammation induced by AVM.
      To our best knowledge, this is the first report to study the toxic effect of AVM
      on inflammatory damage in king pigeon. Thus, the information presented in this
      study is believed to be helpful in supplementing data for further AVM toxicity
      study.

PMID- 24134893
TI  - Characterization and spacial distribution variability of chromophoric dissolved
      organic matter (CDOM) in the Yangtze Estuary.
AB  - The spatial characteristics and the quantity and quality of the chromophoric
      dissolved organic matter (CDOM) in the Yangtze Estuary, based on the abundance,
      degree of humification and sources, were studied using 3D fluorescence excitation
      emission matrix spectra (F-EEMs) with parallel factor and principal component
      analysis (PARAFAC-PCA). The results indicated that the CDOM abundance decreased
      and the aromaticity increased from the upstream to the downstream areas of the
      estuary. Higher CDOM abundance and degrees of humification were observed in the
      pore water than that in the surface and bottom waters. Two humic-like components
      (C1 and C3) and one tryptophan-like component (C2) were identified using the
      PARAFAC model. The separation of the samples by PCA highlighted the differences
      in the DOM properties. Components C1 and C3 concurrently displayed positive
      factor 1 loadings with nearly zero factor 2 loadings, while C2 showed highly
      positive factor 2 loadings. The C1 and C3 were very similar and exhibited a
      direct relationship with A355 and DOC. The CDOM in the pore water increased along
      the river to the coastal area, which was mainly influenced by C1 and C3 and was
      significantly derived from sediment remineralization and deposition from the
      inflow of the Yangtze River. The CDOM in the surface and bottom waters was
      dominated by C2, especially in the inflows of multiple tributaries that were
      affected by intensive anthropogenic activities. The microbial degradation of
      exogenous wastes from the tributary inputs and shoreside discharges were dominant
      sources of the CDOM in the surface and bottom waters.

PMID- 24134894
TI  - UHPLC-MS/MS analysis of arachidonic acid and 10 of its major cytochrome P450
      metabolites as free acids in rat livers: effects of hepatic ischemia.
AB  - The cytochrome P450 metabolites of arachidonic acid (AA) are mostly present in
      tissues, such as the liver, as bound to phospholipids, with only a small fraction
      available as free acids. The purpose of this study was to develop and validate a
      UHPLC-MS/MS method for quantitation of free liver concentrations of AA and four
      epoxygenated (5,6-, 8,9-, 11,12-, and 14,15-EET), four dihydroxylated (5,6-, 8,9
      , 11,12-, and 14,15-DHET), and two omega/(omega-1) hydroxylated (19- and 20
      HETEs) metabolites of AA in rat livers using deuterated internal standards. The
      analytes were rapidly and efficiently (79-92%) recovered from 100mg of fresh
      liver into methanol. After evaporation, the reconstituted samples were injected
      either undiluted (for the simultaneous analysis of the metabolites) into a
      gradient or diluted (for AA analysis) into an isocratic UHPLC system with run
      times of 5 and 2 min, respectively. Mass spectrometry was conducted using
      multiple reaction monitoring in negative mode. The method was linear (r(2)>=
      0.98) in the concentration ranges tested for metabolites (0.19-120 ng/g liver)
      and AA (7.8-500 MUg/g liver). The lower limit of quantitation of the assay was
      between 0.57 and 5.6 pg injected on column for different AA metabolites. The
      assay was validated (n=5) based on acceptable intra- and inter-run accuracy and
      precision values. Additionally, matrix effect was minimal for most analytes.
      Freeze-thaw of samples drastically increased the free liver concentrations of
      analytes, presumably due to their release from the membrane storage sites.
      Therefore, fresh liver samples should be used for analysis. However, the
      methanolic extracts may be stored at -80 degrees C for at least two weeks without
      any compromise. The method was successfully used in the measurement of all the
      analytes in the rats subjected to 60 min of hepatic ischemia (n=6) or sham
      operation (n=6). Ischemia resulted in significantly higher free concentrations of
      AA and most of its studied metabolites. The method is precise, accurate, and
      sensitive for measurement of free liver concentrations of AA and its P450
      metabolites in the rat liver.

PMID- 24134895
TI  - ?
AB  - Riata and Riata ST silicone defibrillation leads are prone to externalization of
      conductors due to inside-out abrasion in the high-voltage system, causing
      structural damage which may be accompanied by electrical failure. These
      situations are easily detected by fluoroscopy or radiology and by inspection of
      intracardiac electrograms and/or measurement of impedance. However, older pulse
      generators do not automatically perform all the measurements needed to assess the
      integrity of the high-voltage electrical system, nor do they have patient
      notifier alerts in case of dysfunction. The authors describe the case of a
      patient in whom structural damage was detected on fluoroscopy during pulse
      generator replacement. They discuss the best strategy in these patients,
      considering current knowledge of this dysfunction.

PMID- 24134896
TI  - Kinematics of marathon running tactics.

PMID- 24134897
TI  - A comparative study on culture conditions and routine expansion of amniotic fluid
      derived mesenchymal progenitor cells.
AB  - BACKGROUND: Amniotic fluid (AF) cell populations will be applied in perinatology.
      We aimed to test the feasibility of large-scale cell expansion. STUDY METHODS: We
      determined the best out of three published expansion protocols for mesenchymal
      progenitors (AF samples, n = 4) in terms of self-renewal ability.
      Characterization was performed based on morphology, surface marker analysis,
      cytogenetic stability, and differentiation potential. The conditions for the best
      self-renewal ability were further determined in a consecutive series (n = 159).
      RESULTS: The medium containing fetal bovine serum (FBS), epidermal growth factor,
      insulin, transferrin, and tri-iodothyronine, combined with seeding on gelatin
      coated wells, best stimulated the growth of cells with mesenchymal features, as
      demonstrated by flow cytometry; however, only osteogenic differentiation was
      possible. Large-scale testing (n = 44) failed to confirm a robust self-renewal
      ability. Better results were obtained (n = 88) using optimized FBS or an
      increased initial cell density. Eventually over 81% of cultures continued growing
      after the initial medium change and had mesenchymal features but failed
      differentiation assays. DISCUSSION: Routine in vitro expansion of AF-derived
      mesenchymal cells remains problematic. Despite an increase in successful cell
      cultures from 40 up to 80% using optimized serum and an increased cell density,
      eventually cells failed to demonstrate differentiation abilities. Routine
      isolation and expansion from unselected AF samples remains a challenge.

PMID- 24134898
TI  - Accuracy of providers' assessment of pain during intrauterine device insertion.
AB  - BACKGROUND: Providers often underestimate patient pain. This study investigated
      if providers accurately assess pain during intrauterine device (IUD) insertion.
      STUDY DESIGN: This is a secondary analysis of a randomized trial. Participants
      rated pain on a 100-mm visual analogue scale (VAS). Providers marked a similar
      VAS for maximum level and timing of participant pain. RESULTS: The mean patient
      maximum pain was 64.8 mm (SD, 27) compared to 35.3 mm (SD, 26) rated by the
      provider (p<.001). Patient and provider agreement on most painful time point of
      procedure was weak (kappa statistic, 0.16). CONCLUSIONS: Providers underestimate
      pain during IUD insertion. IMPLICATIONS: To our knowledge, this is the first
      paper to compare provider and patient perceptions of pain during IUD insertion.
      Understanding this relationship will help guide further research about IUD
      insertion pain and techniques and could improve patient counseling.

PMID- 24134899
TI  - Investigating the correlation between in vivo absorption and in vitro release of
      fenofibrate from lipid matrix particles in biorelevant medium.
AB  - Lipid matrix particles (LMP) may be used as better carriers for poorly water
      soluble drugs than liquid lipid carriers because of reduced drug mobilization in
      the formulations. However, the digestion process of solid lipid particles and
      their effect on the absorption of poorly water-soluble drugs are not fully
      understood. This study aimed at investigating the effect of particle size of LMP
      on drug release in vitro as well as absorption in vivo in order to get a better
      understanding on the effect of degradation of lipid particles on drug
      solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug,
      was incorporated into LMP in this study using probe ultrasound sonication. The
      resultant LMP were characterised in terms of particle size, size distribution,
      zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption
      in rat model. LMP of three different particle sizes i.e. approximately 100 nm,
      400 nm, and 10 MUm (microparticles) were produced with high entrapment
      efficiencies. The in vitro lipolysis study showed that the recovery of
      fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly
      higher (p<0.05) than that of microparticles after 30 min of lipolysis, suggesting
      that nano-sized LMP were digested to a larger extent due to greater specific
      surface area. The 100 nm LMP showed faster initial digestion followed by 400 nm
      LMP and microparticles. The area under the plasma concentration-time curve (AUC)
      following oral administration of 100 nm LMP was significantly higher (p<0.01)
      than that of microparticles and fenofibrate crystalline suspension (control).
      However, no significant difference was observed between the AUCs of 100 nm and
      400 nm LMP. The same rank order on the in vivo absorption and the in vitro
      response was observed. The recovery (%) of fenofibrate partitioning into the
      aqueous phase during in vitro lipolysis and the AUC of plasma concentration-time
      curve of fenofibric acid was in the order of 100 nm LMP>microparticles>control.
      In summary, the present study demonstrated the particle size dependence of
      bioavailability of fenofibrate loaded LMP in rat model which correlates well with
      the in vitro drug release performed in the biorelevant medium.

PMID- 24134900
TI  - Factors associated with fall-related fractures in Parkinson's disease.
AB  - PURPOSE: Fall-related fracture is one of the most disabling features of
      idiopathic Parkinson's disease (PD). A better understanding of the associated
      factors is needed to predict PD patients who will require treatment. METHODS:
      This prospective study enrolled 100 adult idiopathic PD patients. Stepwise
      logistic regressions were used to evaluate the relationships between clinical
      factors and fall-related fracture. RESULTS: Falls occurred in 56 PD patients,
      including 32 with fall-related fractures. The rate of falls in the study period
      was 2.2 +/- 1.4 per 18 months. The percentage of osteoporosis was 34% (19/56) and
      11% in PD patients with and without falls, respectively. Risk factors associated
      with fall-related fracture were sex, underlying knee osteoarthritis, mean Unified
      Parkinson's Disease Rating Scale score, mean Morse fall scale, mean Hoehn and
      Yahr stage, and exercise habit. By stepwise logistic regression, sex and mean
      Morse fall scale were independently associated with fall-related fracture.
      Females had an odds ratio of 3.8 compared to males and the cut-off value of the
      Morse fall scale for predicting fall-related fracture was 72.5 (sensitivity 72%
      and specificity 70%). DISCUSSION: Higher mean Morse fall scales (>72.5) and
      female sex are associated with higher risk of fall-related fractures. Preventing
      falls in the high-risk PD group is an important safety issue and highly relevant
      for their quality of life.

PMID- 24134901
TI  - Targeted therapies in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare disorder characterized by
      progressive obliteration of small pulmonary arteries that leads to elevated
      pulmonary arterial pressure and right heart failure. During the last decades, an
      improved understanding of the pathophysiology of the disease has resulted in the
      development of effective therapies targeting endothelial dysfunction
      (epoprostenol and derivatives, endothelin receptor antagonists and
      phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and
      hemodynamic improvement. Even though, no cure exists for PAH and prognosis
      remains poor. Recently, several additional pathways have been suggested to be
      involved in the pathogenesis of PAH, and may represent innovative therapies. In
      this summary, we review conventional therapy, pharmacological agents currently
      available for the treatment of PAH and the benefit/risk ratio of potential future
      therapies. 

PMID- 24134904
TI  - Design, synthesis and biological evaluation of 3-benzyloxy-linked
      pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs.
AB  - A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a-8s)
      was designed, synthesized and evaluated for their in vitro anti-HIV activity in
      MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1
      replication in the lower micromolar concentration range (EC(50)=0.05-35 MUM) with
      high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h
      and 8g displayed excellent antiretroviral activity against wt HIV-1 with low
      cytotoxicity (EC(50)=0.07 MUM, CC(50) >347 MUM, SI >4870; EC50=0.05 MUM,
      CC(50)=42 MUM, SI=777, respectively), comparable to that of the marked drug
      nevirapine (EC(50)=0.113 MUM, CC(50) >15 MUM, SI >133). In order to confirm the
      binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally,
      preliminary structure activity relationship (SAR) analysis and molecular docking
      studies of newly synthesized compounds were also discussed, as well as the
      predicted physicochemical properties.

PMID- 24134902
TI  - Circulating tumor cells: advances in isolation and analysis, and challenges for
      clinical applications.
AB  - Circulating tumor cells (CTCs) are rare cancer cells released from tumors into
      the bloodstream that are thought to have a key role in cancer metastasis. The
      presence of CTCs has been associated with worse prognosis in several major cancer
      types, including breast, prostate and colorectal cancer. There is considerable
      interest in CTC research and technologies for their potential use as cancer
      biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug
      development, and improve the treatment of cancer patients. This review provides
      an update on recent progress in CTC isolation and molecular characterization
      technologies. Furthermore, the review covers significant advances and limitations
      in the clinical applications of CTC-based assays for cancer prognosis, response
      to anti-cancer therapies, and exploratory studies in biomarkers predictive of
      sensitivity and resistance to cancer therapies. 

PMID- 24134905
TI  - Mass spectrometry-based intraoperative tissue identification in neurosurgery.

PMID- 24134906
TI  - New frontiers in intraoperative tissue diagnosis.

PMID- 24134908
TI  - A requiem for American football? Galen to Camp to Hounsfield.

PMID- 24134907
TI  - Radiation dose reduction in neuroendovascular procedures.

PMID- 24134903
TI  - Imaging aspects of the tumor stroma with therapeutic implications.
AB  - Cancer cells rely on extensive support from the stroma in order to survive,
      proliferate and invade. The tumor stroma is thus an important potential target
      for anti-cancer therapy. Typical changes in the stroma include a shift from the
      quiescence promoting-antiangiogenic extracellular matrix to a provisional matrix
      that promotes invasion and angiogenesis. These changes in the extracellular
      matrix are induced by changes in the secretion of extracellular matrix proteins
      and glucose amino glycans, extravasation of plasma proteins from hyperpermeable
      vessels and release of matrix modifying enzymes resulting in cleavage and cross
      linking of matrix macromolecules. These in turn alter the rigidity of the matrix
      and the exposure and release of cytokines. Changes in matrix rigidity and vessel
      permeability affect drug delivery and mediate resistance to cytotoxic therapy.
      These stroma changes are brought about not only by the cancer cells, but also
      through the action of many cell types that are recruited by tumors including
      immune cells, fibroblasts and endothelial cells. Within the tumor, these normal
      host cells are activated resulting in loss of inhibitory and induction of cancer
      promoting activities. Key to the development of stroma-targeted therapies,
      selective biomarkers were developed for specific imaging of key aspects of the
      tumor stroma. 

PMID- 24134909
TI  - Invalidating human gene patenting: the U.S. Supreme Court rules in Association
      for Molecular Pathology v. Myriad Genetics.

PMID- 24134910
TI  - Self-portrait with a grey felt hat (1886-1887) by Vincent van Gogh (1853-1890).

PMID- 24134911
TI  - Gamete quality of streaked prochilod Prochilodus lineatus (Characiformes) after
      GnRHa and dopamine antagonist treatment.
AB  - The efficiency of OvaprimTM salmon gonadotropin-releasing hormone agonist (GnRHa)
      and dopamine antagonist on the induction of spawning and spermiation in
      Prochilodus lineatus in comparison with the commonly used method using pituitary
      extract (PE) was evaluated. Females received PE at 0.5 + 5.0 mg/kg and OvaprimTM
      at 0.05 + 0.45 ml/kg or at 0.125 + 0.375 ml/kg. All males received a first dose
      of PE at 0.4 mg/kg and then PE at 4.0 mg/kg or OvaprimTM at 0.25 ml/kg. Oocyte,
      egg, larvae and sperm quality were evaluated. All females spawned and oocyte, egg
      and larvae quality were similar between OvaprimTM-treated (both doses) and PE
      treated females. Data from females were pooled and the mean values were: 242 g
      ova weight, 15% ova index, 1209 oocytes/g ova, 284,539 oocytes/female, 183
      oocytes/g body weight, 1.18 mm oocyte diameter, 49% fertilization rate, 43%
      hatching rate and 89% normal larvae. Sperm quality was similar between OvaprimTM
      treated and PE-treated males. Data from males were pooled and the mean values of
      semen were: volume of 3.0 ml, 14.9 * 109 sperm/ml, osmolality of 283 mOsm/kg, pH
      of 7.4, 71% motile sperm, 217 MUm/s curvilinear velocity, 102 MUm/s straight-line
      velocity and 189 MUm/s average path velocity. OvaprimTM treatment can be used for
      commercial reproduction of P. lineatus, without any loss of gamete quality in
      comparison with PE treatment. 

PMID- 24134912
TI  - The lignan glycosides lyoniside and saracoside poison the unusual type IB
      topoisomerase of Leishmania donovani and kill the parasite both in vitro and in
      vivo.
AB  - Lignans are diphenyl propanoids with vast range of biological activities. The
      present study provides an important insight into the anti-leishmanial activities
      of two lignan glycosides, viz. lyoniside and saracoside. These compounds inhibit
      catalytic activities of topoisomerase IB (LdTopIB) of Leishmania donovani in non
      competitive manner and stabilize the LdTopIB mediated cleavage complex formation
      both in vitro and in Leishmania promastigotes and subsequently inhibit the
      religation of cleaved strand. These two compounds not only poison LdTopIB but
      also can interact with the free enzyme LdTopIB. We have also shown that lyoniside
      and saracoside are cytotoxic to promastigotes and intracellular amastigotes. The
      protein-DNA complex formation leads to double strand breaks in DNA which
      ultimately triggers apoptosis-like cell death in the parasite. Along with their
      cytotoxicity towards sodium antimony gluconate (SAG) sensitive AG83 strain, their
      ability to kill SAG resistant GE1 strain makes these two compounds potential anti
      leishmanial candidates. Not only they effectively kill L. donovani amastigotes
      inside macrophages in vitro, lyoniside and saracoside demonstrated strong anti
      leishmanial efficacies in BALB/c mice model of leishmaniasis. Treatment with
      these lignan glycosides produce nitric oxide and reactive oxygen species which
      result in almost complete clearance of the liver and splenic parasite burden.
      These compounds do not inhibit human topoisomerase IB upto 200MUM concentrations
      and had poor cytotoxic effect on uninfected cultured murine peritoneal
      macrophages upto 100MUM concentrations. Taken together it can be concluded that
      these compounds can be developed into excellent therapeutic agent against deadly
      disease leishmaniasis. 

PMID- 24134913
TI  - Morin reduces hepatic inflammation-associated lipid accumulation in high fructose
      fed rats via inhibiting sphingosine kinase 1/sphingosine 1-phosphate signaling
      pathway.
AB  - SphK1/S1P signaling pathway is involved in the development of hepatic
      inflammation and injury. But its role in high fructose-induced NAFLD has not yet
      been reported. The aim of this study was to elucidate the crucial role of
      SphK1/S1P signaling pathway in high fructose-induced hepatic inflammation and
      lipid accumulation in rats. Moreover, the hepatoprotective effects of morin, a
      flavonoid with anti-inflammatory and anti-hyperlipedimic activities, on these
      hepatic changes in rats were investigated. High fructose-fed rats were orally
      treated with morin (30 and 60mg/kg) and pioglitazone (4mg/kg) for 8 weeks,
      respectively. Fructose feeding induced hyperlipidemia, and activated SphK1/S1P
      signaling pathway characterized by the elevation of SphK1 activity, S1P
      production as well as SphK1, S1PR1 and S1PR3 protein levels, which in turn caused
      NF-kappaB signaling activation to produce IL-1beta, IL-6 and TNF-alpha and
      inflammation in the liver of rats. Subsequently, hepatic insulin and leptin
      signaling impairment and lipid metabolic disorder were observed in this animal
      model, resulting in liver lipid accumulation. Morin restored high fructose
      induced the activation of hepatic SphK1/S1P signaling pathway in rats.
      Subsequently, the reduced NF-kappaB signaling activation by morin decreased
      inflammatory cytokine production, recovered insulin and leptin signaling
      impairment to reduce lipid accumulation and injury in the rat liver. These
      effects of morin were confirmed in Buffalo rat liver (BRL3A) cell model
      stimulated with 5mM fructose. Thus, the inhibition of hepatic SphK1/S1P signaling
      pathway may be a novel mechanism by which morin exerts hepatoprotection in high
      fructose-fed rats, possibly involving liver inflammation inhibition and lipid
      accumulation recovery. 

PMID- 24134914
TI  - Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as
      well as in tumorogenesis.
AB  - Epigenetic mechanisms such as DNA methylation and histone posttranslational
      modifications, allow cells to maintain the phenotype throughout successive
      mitosis. UHRF1 plays a major role in the inheritance of some epigenetic marks
      from mother cells to daughter cells due to its particular structural domains. The
      originality of UHRF1 lies in the fact that it can read epigenetic marks and
      recruit the enzymes that catalyze the same epigenetic mark. The SRA domain senses
      the presence of a methylated cytosine on one DNA strand allowing the recruitment
      of DNMT1, which methylates the cytosine on the newly synthesized DNA. The
      recently identified tudor domain of UHRF1 senses the presence of methylated
      histone H3 conducting UHRF1 to recruit histone methyltransferases. Recent studies
      deciphering the relationships between some of the structural domains of UHRF1
      provides new insights on the reading of the epigenetic code over a larger portion
      of histone tail than usually expected. Furthermore, latest developments
      highlights that UHRF1 is one of the proteins which is able to directly connect
      DNA methylation to histone epigenetic marks. This paper reviews the principles
      how UHRF1 acts as an epigenetic reader and discusses the properties of UHRF1 to
      be a biomarker as well as a therapeutic target. 

PMID- 24134915
TI  - The O-methylation of chrysin markedly improves its intestinal anti-inflammatory
      properties: Structure-activity relationships of flavones.
AB  - The aim of this study was to investigate whether methoxylated flavones versus
      their unmethylated analogs can modulate the intestinal inflammatory response.
      Flavone effects were assessed on soluble pro-inflammatory mediator (IL-8, IL-6,
      macrophage chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2)
      derived PGE2) production and on nuclear factor (NF)-kappaB activation in 3d
      confluent and 21d-differentiated Caco-2 cells stimulated with interleukin (IL)
      1beta. Chrysin (CHRY) showed anti-inflammatory properties by decreasing COX-2
      derived PGE2 and reducing NF-kappaB activation. Compared to CHRY, the
      dimethoxylated form (CHRY-DM) significantly reduced the secretion of all pro
      inflammatory mediators, except IL-8, at both cellular stages (P<0.05); these
      effects being dose-dependent in 3d-cells. The reduction of NF-kappaB activation
      was significantly more pronounced with CHRY-DM. By evaluating other flavones, it
      was established that several structural dispositions of flavones seemed to be
      determinant in order to attenuate the intestinal inflammatory response, such as
      methoxylation of the 5- and 7-hydroxyl groups on the A-ring, non-methoxylation of
      the 3'-hydroxyl groups on the B-ring, and methoxylation of the 3-hydroxyl group
      on the C-ring. Of all flavones examined, CHRY-DM exhibited the strongest anti
      inflammatory activity. These data indicate that, in the Caco-2 cell model,
      methoxylation of CHRY greatly improves its anti-inflammatory properties, probably
      through a more pronounced inhibition of the NF-kappaB signaling pathway.
      Nevertheless, methoxylation of other flavones was not systematically beneficial. 

PMID- 24134917
TI  - Modeling stomatal conductance and ozone uptake of Fagus crenata grown under
      different nitrogen loads.
AB  - A multiplicative stomatal conductance model was constructed to estimate stomatal
      O3 uptake of Fagus crenata exposed to O3 under different N loads to the soil. Our
      stomatal conductance model included environmental functions such as the stomatal
      responses of F. crenata to diurnal changes, chronic O3 stress (AOT0), acute O3
      stress (O3 concentration), and nitrogen load to soil. The model could explain 62%
      of the variability in stomatal conductance. We suggest therefore that stomatal
      closure induced by O3 and N load-induced soil acidification must be taken into
      account in developing a stomatal conductance model for estimating stomatal O3
      uptake for future risk assessment of O3 impact on Japanese forest tree species
      such as F. crenata. 

PMID- 24134916
TI  - Individual karyotypes at the origins of cervical carcinomas.
AB  - BACKGROUND: In 1952 Papanicolaou et al. first diagnosed and graded cervical
      carcinomas based on individual "abnormal DNA contents" and cellular phenotypes.
      Surprisingly current papilloma virus and mutation theories of carcinomas do not
      mention these individualities. The viral theory holds that randomly integrated,
      defective genomes of papilloma viruses, which are often untranscribed, cause
      cervical carcinomas with unknown cofactors 20-50 years after infection. Virus
      free carcinomas are attributed to mutations of a few tumor-suppressor genes,
      especially the p53 gene. But the paradox of how a few mutations or latent
      defective viral DNAs would generate carcinomas with endless individual DNA
      contents, degrees of malignancies and cellular phenotypes is unsolved. Since
      speciation predicts individuality, we test here the theory that cancers are
      autonomous species with individual clonal karyotypes and phenotypes. This theory
      postulates that carcinogens induce aneuploidy. By unbalancing mitosis genes
      aneuploidy catalyzes chain reactions of karyotypic evolutions. Most such
      evolutions end with non-viable karyotypes but a few become new cancer karyotypes.
      Despite congenitally unbalanced mitosis genes cancer karyotypes are stabilized by
      clonal selections for cancer-specific autonomy. RESULTS: To test the prediction
      of the speciation theory that individual carcinomas have individual clonal
      karyotypes and phenotypes, we have analyzed here the phenotypes and karyotypes of
      nine cervical carcinomas. Seven of these contained papilloma virus sequences and
      two did not. We determined phenotypic individuality and clonality based on the
      morphology and sociology of carcinoma cells in vitro. Karyotypic individuality
      and clonality were determined by comparing all chromosomes of 20 karyotypes of
      carcinomas in three-dimensional arrays. Such arrays list chromosome numbers on
      the x-axis, chromosome copy numbers on the y-axis and the number of karyotypes
      arrayed on the z-axis. We found (1) individual clonal karyotypes and phenotypes
      in all nine carcinomas, but no virus-specific markers, (2) 1-to-1 variations
      between carcinoma-specific karyotypes and phenotypes, e.g. drug-resistance and
      cell morphology, (3) proportionality between the copy numbers of chromosomes and
      the copy numbers of hundreds of over- and under-expressed mRNAs, (4) evidence
      that tobacco-carcinogens induce cervical carcinomas via aneuploidy, consistent
      with the speciation theory. CONCLUSIONS: Since the individual clonal karyotypes
      of nine carcinomas correlated and co-varied 1-to-1 with complex individual
      transcriptomes and phenotypes, we have classical genetic and functional
      transcriptomic evidence to conclude that these karyotypes encode carcinomas -
      much like the clonal karyotypes that encode conventional species. These
      individual karyotypes explain the individual "DNA contents", the endless grades
      of malignancies and the complex individual transcriptomes and phenotypes of
      carcinomas.

PMID- 24134919
TI  - Audit of referral pathways in the diagnosis of lung cancer: a pilot study.
AB  - This pilot study sought to describe the diagnostic pathways for patients with
      lung cancer and explore the feasibility of a medical record audit for this
      purpose. An audit of 25 medical records of patients with a confirmed diagnosis of
      lung cancer was conducted, at a single outer metropolitan hospital in Victoria.
      Patients were presented to secondary care from general practice (n=17, 68%), the
      emergency department (n=3, 12%) or specialist rooms (n=1, 4%). Those who
      journeyed through general practice experienced the longest median intervals to
      diagnosis (20 days, interquartile range 7-47). The majority of patients (n=15,
      60%) were referred by a specialist to a multidisciplinary team after a diagnosis
      had been confirmed but before treatment commenced. These patients waited a median
      of 20 days from their first specialist appointment to a multidisciplinary team
      appointment. This research illustrated that a variety of pathways to diagnosis
      exist. Critically, it requires patient data and additional auditing of primary,
      public and private health sector records to determine generalisability of
      findings and the effectiveness of a medical record audit as a data collection
      tool. 

PMID- 24134918
TI  - Adolescent social defeat decreases spatial working memory performance in
      adulthood.
AB  - BACKGROUND: Adolescent social stress is associated with increased incidence of
      mental illnesses in adulthood that are characterized by deficits in cognitive
      focus and flexibility. Such enhanced vulnerability may be due to psychosocial
      stress-induced disruption of the developing mesocortical dopamine system, which
      plays a fundamental role in facilitating complex cognitive processes such as
      spatial working memory. Adolescent rats exposed to repeated social defeat as a
      model of social stress develop dopaminergic hypofunction in the medial prefrontal
      cortex as adults. To evaluate a direct link between adolescent social stress and
      later deficits in cognitive function, the present study tested the effects of
      adolescent social defeat on two separate tests of spatial working memory
      performance. METHODS: Adult rats exposed to adolescent social defeat and their
      controls were trained on either the delayed win-shift task or the delayed
      alternating T-Maze task and then challenged with various delay periods. To
      evaluate potential differences in motivation for the food reward used in memory
      tasks, consumption and conditioned place preference for sweetened condensed milk
      were tested in a separate cohort of previously defeated rats and controls.
      RESULTS: Compared to controls, adult rats defeated in adolescence showed a delay
      dependent deficit in spatial working memory performance, committing more errors
      at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively.
      Observed memory deficits were likely independent of differences in reward
      motivation, as conditioned place preference for the palatable food used on both
      tasks was similar between the adolescent social defeat group and control.
      CONCLUSIONS: The results demonstrate that severe social stressors during
      adolescence can produce long term deficits in aspects of cognitive function.
      Given the dependence of spatial working memory on prefrontal dopamine,
      pharmacologically reversing dopaminergic deficiencies caused by adolescent social
      stress has the potential to treat such cognitive deficits.

PMID- 24134920
TI  - Survival of Shiga toxin-producing Escherichia coli and Stx bacteriophages in
      moisture enhanced beef.
AB  - Moisture enhancement of meat through injection is a technology to improve the
      sensory properties and the weight of meat. However, the technology may increase
      the risk of food borne infections. Shiga toxin-producing Escherichia coli (STEC)
      or bacteriophages carrying cytotoxin genes (Shiga toxin genes, stx), which is
      normally only present on the surface of intact beef, may be transferred to the
      inner parts of the muscle during the injection process. Pathogens and
      bacteriophages surviving the storage period may not be eliminated in the cooking
      process since many consumers prefer undercooked beef. Measures to increase the
      microbial food safety of moisture enhanced beef may include sterilization or
      washing of the outer surface of the meat before injection, avoiding recycling of
      marinade and addition of antimicrobial agents to the marinade. This paper reviews
      the literature regarding microbial safety of moisture enhanced beef with special
      emphasis on STEC and Stx bacteriophages. Also, results from a European Union
      research project, ProSafeBeef (Food-CT-16 2006-36241) are presented. 

PMID- 24134921
TI  - Expression of calcium-binding proteins in layer 1 reelin-immunoreactive cells
      during rat and mouse neocortical development.
AB  - Cajal-Retzius cells in layer 1 of the developing cerebral cortex and their
      product of secretion, reelin, an extracellular matrix protein, play a crucial
      role in establishing the correct lamination pattern in this tissue. As many
      studies into reelin signaling routes and pathological alterations are conducted
      in murine models, we used double-labeling and confocal microscopy to compare the
      distribution of the cell-specific markers, calretinin and calbindin, in reelin
      immunoreactive cells during postnatal rat and mouse neocortical development. In
      the rat, neither calretinin nor calbindin colocalized with reelin in Cajal
      Retzius cells at P0-P2. From P5 to P14, the colocalization of reelin and
      calretinin was commonly found in presumptive rat subpial piriform cells. These
      cells progressively lacked calretinin expression and persisted into adulthood as
      part of the pool of layer 1 reelin-positive interneurons. Conversely, in the
      mouse, reelin-immunoreactive Cajal-Retzius cells colocalized with calretinin
      and/or calbindin. Subpial piriform cells containing reelin and calretinin were
      identified at P5-P7, but lacked calretinin expression at P14. In adult mice, as
      in the rat, reelin-immunoreactive cells did not colocalize with calcium-binding
      proteins. Our results reveal a complex neurochemical profile of layer 1 cells in
      the rat neocortex, which makes using a single calcium-binding protein as a marker
      of rodent reelin-immunoreactive cells difficult. 

PMID- 24134922
TI  - The impact of performance incentives on child health outcomes: results from a
      cluster randomized controlled trial in the Philippines.
AB  - Improving clinical performance using measurement and payment incentives,
      including pay for performance (or P4P), has, so far, shown modest to no benefit
      on patient outcomes. Our objective was to assess the impact of a P4P programme on
      paediatric health outcomes in the Philippines. We used data from the Quality
      Improvement Demonstration Study. In this study, the P4P intervention, introduced
      in 2004, was randomly assigned to 10 community district hospitals, which were
      matched to 10 control sites. At all sites, physician quality was measured using
      Clinical Performance Vignettes (CPVs) among randomly selected physicians every 6
      months over a 36-month period. In the hospitals randomized to the P4P
      intervention, physicians received bonus payments if they met qualifying scores on
      the CPV. We measured health outcomes 4-10 weeks after hospital discharge among
      children 5 years of age and under who had been hospitalized for diarrhoea and
      pneumonia (the two most common illnesses affecting this age cohort) and had been
      under the care of physicians participating in the study. Health outcomes data
      collection was done at baseline/pre-intervention and 2 years post-intervention on
      the following post-discharge outcomes: (1) age-adjusted wasting, (2) C-reactive
      protein in blood, (3) haemoglobin level and (4) parental assessment of child's
      health using general self-reported health (GSRH) measure. To evaluate changes in
      health outcomes in the control vs intervention sites over time (baseline vs post
      intervention), we used a difference-in-difference logistic regression analysis,
      controlling for potential confounders. We found an improvement of 7 and 9
      percentage points in GSRH and wasting over time (post-intervention vs baseline)
      in the intervention sites relative to the control sites (P <= 0.001). The results
      from this randomized social experiment indicate that the introduction of a
      performance-based incentive programme, which included measurement and feedback,
      led to improvements in two important child health outcomes. 

PMID- 24134923
TI  - Effect of adenomyosis on in vitro fertilization/intracytoplasmic sperm injection
      outcomes in infertile women: a retrospective cohort study.
AB  - AIMS: To study the effect of adenomyosis on in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile
      patients. METHODS: We performed a retrospective, database-searched cohort study
      based on 10,268 patients undergoing controlled ovarian hyperstimulation and
      IVF/ICSI between 2009 and 2011 in our unit. Adenomyosis was diagnosed by
      transvaginal ultrasound. A high-quality matched cohort study with strict
      inclusion criteria was conducted. We compared the basic characteristics and main
      IVF/ICSI outcomes between the two groups. RESULTS: We identified 83 patients with
      adenomyosis, of whom we included 77, and strictly matched them to 77 patients
      without adenomyosis. Higher day 3 estrogen levels and a longer duration of
      gonadotropin stimulation days were found in women with adenomyosis compared to
      control subjects. Patients with adenomyosis had a nonsignificant trend toward a
      lower clinical pregnancy rate and a higher miscarriage rate (p = 0.103 and 0.09,
      respectively). The delivery rate was significantly lower in the adenomyosis group
      in comparison to the matched controls (p = 0.022). CONCLUSIONS: Within the
      limitations of a retrospective study (albeit with a remarkably large number of
      observations), our results suggest that transvaginal ultrasound-diagnosed
      adenomyosis could have a negative impact on the main IVF/ICSI outcomes. Improving
      the diagnostic validity and scoring of disease severity in patients with
      adenomyosis is suggested.

PMID- 24134925
TI  - Effect of metabolic syndrome or its components on cardiovascular disease events -
      Maintaining statistical power.

PMID- 24134924
TI  - Asymmetry in stimulus and response conflict processing across the adult lifespan:
      ERP and EMG evidence.
AB  - Several studies have shown that conflict processing improves from childhood to
      adulthood and declines from adulthood to old age. However the neural mechanisms
      underlying this lifespan asymmetry were previously unexplored. We combined event
      related potentials (ERPs) and electromyography (EMG) to examine lifespan changes
      in stimulus and response conflict processing using a modified Stroop task. We
      used a Stroop task that a priori dissociated stimulus and response conflict.
      Delayed P3b latency and increased amplitude revealed that middle age adults have
      a deficit in stimulus processing. Additionally a sustained P3a across frontal and
      central electrodes occurred only in middle age adults indicating the recruitment
      of frontal activity. Conversely, decreased lateralized readiness potential (LRP)
      amplitude and increased EMG activity in the incorrect hand in adolescents reveal
      protracted development of response processing into late adolescence. The N450, a
      measure of conflict processing, was found to be sensitive to both stimulus and
      response conflict. Altogether these results provide evidence for asymmetrical
      differences in stimulus and response conflict processing across adolescence,
      young adulthood and middle age.

PMID- 24134926
TI  - Metabolic control of hyaluronan synthases.
AB  - Hyaluronan (HA) is a glycosaminoglycan composed by repeating units of D
      glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc) that is ubiquitously
      present in the extracellular matrix (ECM) where it has a critical role in the
      physiology and pathology of several mammalian tissues. HA represents a perfect
      environment in which cells can migrate and proliferate. Moreover, several
      receptors can interact with HA at cellular level triggering multiple signal
      transduction responses. The control of the HA synthesis is therefore critical in
      ECM assembly and cell biology; in this review we address the metabolic regulation
      of HA synthesis. In contrast with other glycosaminoglycans, which are synthesized
      in the Golgi apparatus, HA is produced at the plasma membrane by HA synthases
      (HAS1-3), which use cytoplasmic UDP-glucuronic acid and UDP-N-acetylglucosamine
      as substrates. UDP-GlcUA and UDP-hexosamine availability is critical for the
      synthesis of GAGs, which is an energy consuming process. AMP activated protein
      kinase (AMPK), which is considered a sensor of the energy status of the cell and
      is activated by low ATP:AMP ratio, leads to the inhibition of HA secretion by
      HAS2 phosphorylation at threonine 110. However, the most general sensor of
      cellular nutritional status is the hexosamine biosynthetic pathway that brings to
      the formation of UDP-GlcNAc and intracellular protein glycosylation by O-linked
      attachment of the monosaccharide beta-N-acetylglucosamine (O-GlcNAcylation) to
      specific aminoacid residues. Such highly dynamic and ubiquitous protein
      modification affects serine 221 residue of HAS2 that lead to a dramatic
      stabilization of the enzyme in the membranes. 

PMID- 24134927
TI  - The Journal of Arthroplasty has published the Asia-Pacific issue biennially since
      2005. Introduction.

PMID- 24134928
TI  - Decreasing total joint implant costs and physician specific cost variation
      through negotiation.
AB  - Reducing the cost of total joint implants can significantly reduce the cost of an
      episode of care without affecting the quality. In 2011 we began a program to
      decrease and standardize the pricing of total joint implants. In the first year
      of the intervention we preformed 1,090 and 1,022 unilateral total knee and total
      hip arthroplasties respectively. Based on our volume and pricing data, our
      institution saved over $2 million during the first year of this intervention. It
      is clear that our initiative to negotiate lower implant cost with our vendors has
      lead to a significant reduction in the cost of joint arthroplasties and a
      reduction in the variability in costs between physicians. 

PMID- 24134929
TI  - Ovarian complete hydatidiform mole: case study with molecular analysis and review
      of the literature.
AB  - Ectopic complete molar pregnancy in the ovary is an exceptionally rare event.
      Here we present a case of ovarian complete hydatidiform mole in a 20-year-old
      gravida 2 para 1 woman. At presentation, the patient underwent excision of a
      hemorrhagic left ovarian cyst, with routine sections demonstrating a hemorrhagic
      corpus luteum with a single microscopic focus of detached atypical trophoblast,
      without chorionic villi. Subsequent left salpingo-oophorectomy for persistently
      elevated human chorionic gonadotropin led to a final diagnosis of complete
      hydatidiform mole arising in the ovary. The fallopian tube was unremarkable.
      Zygosity was determined using short tandem repeat analysis, confirming the
      diagnosis of monospermic complete mole. In the clinical setting of a markedly
      elevated human chorionic gonadotropin level and an ovarian mass, histopathologic
      examination is critical in distinguishing ectopic pregnancy from choriocarcinoma.
      Short tandem repeat analysis can be a useful adjunct to histologic diagnosis in
      challenging cases. 

PMID- 24134930
TI  - An immunohistochemical and molecular analysis of problematic and unclassified
      ovarian sex cord-stromal tumors.
AB  - Most ovarian sex cord-stromal tumors (SCSTs) can be categorized on the basis of
      conventional histology, but approximately 10% of cases are unclassified because
      they present indeterminate or overlapping morphologic features.
      Immunohistochemical and molecular studies of unclassified ovarian SCST are very
      limited, but recently, it has been demonstrated that 2 major subgroups of SCST,
      adult-type granulosa cell tumor and Sertoli-Leydig cell tumor, are characterized
      by somatic mutations in FOXL2 and DICER1, respectively. In this study, 12
      diagnostically problematic ovarian SCST, including 9 unclassified tumors, were
      investigated for FOXL2 and DICER1 mutations and for immunohistochemical
      expression of calretinin, CD56, CD99, estrogen receptor alpha, estrogen receptor
      beta, FOXL2, inhibin, progesterone receptor, and steroidogenic factor-1. Four of
      11 tumors with satisfactory analysis showed a FOXL2 mutation; 3 of these cases
      were reported initially as unclassified SCST and 1 as Sertoli-Leydig cell tumor.
      Conversely, 3 cases with an original diagnosis of granulosa cell tumor were FOXL2
      mutation-negative, and none of 7 tumors with satisfactory analysis demonstrated a
      DICER1 mutation. All tumors expressed at least 4 of the immunomarkers examined,
      although staining was often focal and there was no consistent correlation with
      tumor morphology. In conclusion, molecular analysis is useful in the assessment
      of diagnostically challenging ovarian SCST. The absence of FOXL2 and DICER1
      mutations in most unclassified SCST suggests that these could represent a
      distinct tumor subgroup with different molecular pathogenesis.
      Immunohistochemical profiles overlap with those of better categorized SCST, but
      staining may be focal or negative emphasizing the requirement for antibody panels
      in diagnostic assessment. 

PMID- 24134931
TI  - Immunohistochemical profile of the penile urethra and differential expression of
      GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.
AB  - The penile urethra has a distinctive morphology not yet fully characterized by
      immunohistochemistry. In addition, both urothelial and squamous cell carcinomas
      have been reported in the penile urethra, and the distinction between these 2
      tumors might be difficult. The purposes of this study are to assess the histology
      and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra
      and to assess the usefulness of Trans-acting T-cell-specific transcription factor
      (GATA3) and human papillomavirus detection in distinguishing urothelial versus
      squamous cell carcinomas. Normal penile urethra was evaluated in 11 total
      penectomies. The penile urethra was lined by 2 cell layers: a superficial single
      layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7
      , CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial
      differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of
      primary tumors of the penile urethra (3 urothelial and 3 squamous cell
      carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of
      25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas
      were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial
      carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was
      detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial
      carcinomas. In conclusion, the penile urethra is covered by epithelial cells that
      are unique in morphology and immunohistochemical profile. In addition, our study
      suggests that GATA3 and human papillomavirus detection are useful markers for
      distinguishing urothelial carcinomas from squamous cell carcinomas of the penile
      urethra. 

PMID- 24134932
TI  - 9p21 gene locus in Spitz nevi of older individuals: absence of cytogenetic and
      immunohistochemical findings associated with malignancy.
AB  - The diagnosis of Spitz nevus in an elderly individual is often met with
      skepticism because the lesion can be difficult to distinguish from melanoma and
      because the probability of a malignant melanoma is higher in older patients.
      Recently, increased sensitivity for detection of malignant spitzoid neoplasms
      using 9p21 fluorescence in situ hybridization (FISH) has been described. In this
      study, we address the question of whether histopathologically typical Spitz nevi
      occurring in patients 50 years and older show any abnormalities regarding the
      9p21 CDKN2A tumor suppressor gene locus. p16 immunohistochemistry (IHC), as well
      as dual-color FISH for assessment of diploid or hypodiploid status at 9p21, was
      performed in 25 classic Spitz nevi from patients 50 years and older and was
      compared with findings in a younger control population. All cases of typical
      Spitz nevi occurring in older patients retained p16 expression by
      immunohistochemistry and showed normal, diploid 9p21 FISH signals. Heterozygous
      loss of 9p21 by FISH was noted in a control case of a 9-year-old girl and is of
      unknown significance. These findings indicate that p16 expression by
      immunohistochemistry in classic Spitz nevi correlates well with absence of
      malignancy-associated cytogenetic abnormalities at 9p21 by FISH independent of
      the patient's age. Assessment of p16 expression by standard immunohistochemistry
      may therefore be reassuring in routine clinical practice when the patient is of
      advanced age, and can be helpful as a screening tool to select IHC-negative cases
      for extended FISH analysis targeting the 9p21 gene locus. 

PMID- 24134933
TI  - Analysis of MAML2 rearrangement in mucoepidermoid carcinoma of the thymus.
AB  - Primary thymic mucoepidermoid carcinoma (TMEC) is rare. High-grade TMEC can be
      difficult to distinguish from poorly differentiated squamous cell carcinoma and
      adenosquamous carcinoma. A strong association between mucoepidermoid carcinoma
      (MEC) and t(11;19)(q21;p13) has been observed in other anatomical sites. Although
      this translocation is largely considered a disease-defining event for MEC, its
      incidence in TMEC has not been explored. In this study, we evaluate the value of
      identifying MAML2 rearrangement by fluorescence in situ hybridization (FISH) to
      distinguish TMEC from poorly differentiated squamous cell carcinoma and
      adenosquamous carcinoma. Cases of TMEC, moderate to poorly differentiated
      squamous cell carcinoma, and adenosquamous carcinoma were re-reviewed by 3
      surgical pathologists and classified according to the current World Health
      Organization classification of thymic tumors (2004). Cases of TMEC were
      histologically graded using the Brandwein system. FISH was used to detect MAML2
      rearrangements using a break-apart probe. FISH for MAML2 rearrangement was
      performed on cases of TMEC (n = 2), thymic squamous cell carcinoma (n = 5), and
      thymic adenosquamous carcinoma (n = 3). The 2 cases of TMEC showed MAML2
      rearrangement. All other tested cases did not show rearrangement of MAML2. In
      conclusion, using FISH to identify MAML2 rearrangement is a valuable diagnostic
      tool in the evaluation of thymic malignancies, specifically, distinguishing TMEC
      from squamous cell carcinoma and adenosquamous carcinoma. These findings also
      suggest that TMEC has both histomorphologic and cytogenetic similarities to cases
      of MEC arising from other anatomical sites. 

PMID- 24134934
TI  - Gene profiling suggests a common evolution of bladder cancer subtypes.
AB  - BACKGROUND: Bladder cancer exists as several distinct subtypes, including
      urothelial carcinoma (UCa), squamous cell carcinoma (SCCa), adenocarcinoma and
      small cell carcinoma. These entities, despite showing distinct morphology and
      clinical behavior, arise from the urothelial lining and are often accompanied by
      similar precursor/in situ findings. The relationship between these subtypes has
      not been explored in detail. METHODS: We compared gene expression analysis of the
      two most common subtypes of bladder cancer, UCa (n = 10) and SCCa (n = 9), with
      an additional comparison to normal urothelium from non-cancer patients (n = 8)
      using Affymetrix GeneChip Human genome arrays (Affymetrix, Santa Clara, CA). The
      results were stratified by supervised and unsupervised clustering analysis, as
      well as by overall fold change in gene expression. RESULTS: When compared to
      normal urothelium, UCa showed differential expression of 155 genes using a 5-fold
      cut-off. Examples of differentially regulated genes included topoisomerases,
      cancer-related transcription factors and cell cycle mediators. A second
      comparison of normal urothelium to SCCa showed differential expression of 503
      genes, many of which were related to squamous-specific morphology (desmosomal
      complex, intermediate filaments present within squamous epithelium, squamous
      cornifying proteins, and molecules upregulated in squamous carcinomas from other
      anatomic sites). When compared, 137 genes were commonly dysregulated in both UCa
      and SCCa as compared to normal urothelium. All dysregulated genes in UCa were
      shared in common with SCCa, with the exception of only 18 genes. Supervised
      clustering analysis yielded correct classification of lesions in 26/27 (96%) of
      cases and unsupervised clustering analysis yielded correct classification in
      25/27 (92.6%) of cases. CONCLUSIONS: The results from this analysis suggest that
      bladder SCCa shares a significant number of gene expression changes with
      conventional UCa, but also demonstrates an additional set of alterations that is
      unique to this entity that defines the squamous phenotype. The similarity in
      deregulated gene products suggests that SCCa may be a much more closely related
      entity at the molecular level to conventional UCa than previously hypothesized.

PMID- 24134935
TI  - Involvement of L(-)-rhamnose in sea urchin gastrulation: a live embryo assay.
AB  - The sea urchin embryo is a National Institutes of Health model system that has
      provided major developments, and is important in human health and disease. To
      obtain initial insights to identify glycans that mediate cellular interactions,
      Lytechinus pictus sea urchin embryos were incubated at 24 or 30 h post
      fertilization with 0.0009-0.03 M alpha-cyclodextrin, melibiose, L(-)-rhamnose,
      trehalose, D(+)-xylose or L(-)-xylose in lower-calcium artificial sea water (pH
      8.0, 15 degrees C), which speeds the entry of molecules into the interior of the
      embryos. While alpha-cyclodextrin killed the embryos, and L(-)-xylose had small
      effects at one concentration tested, L(-)-rhamnose caused substantially increased
      numbers of unattached archenterons and exogastrulated embryos at low glycan
      concentrations after 18-24 h incubation with the sugar. The results were
      statistically significant compared with the control embryos in the absence of
      sugar (P < 0.05). The other sugars (melibiose, trehalose, D(+)-xylose) had no
      statistically significant effects whatsoever at any of the concentrations tested.
      In total, in the current study, 39,369 embryos were examined. This study is the
      first demonstration that uses a live embryo assay for a likely role for L(-)
      rhamnose in sea urchin gastrula cellular interactions, which have interested
      investigators for over a century.

PMID- 24134936
TI  - Characterization of genotypes among bovine viral diarrhea virus type 1 strains
      according to palindromic nucleotide substitutions in the genomic 5'-untranslated
      region.
AB  - Two-hundred and eighty-one strains of bovine viral diarrhea virus type 1 (BVDV-1)
      were evaluated according to the palindromic nucleotide substitutions (PNS)
      method, a simple and practical genotyping procedure, at the three variable loci,
      V1, V2 and V3, in the 5'-untranslated region of genomic RNA. Ten PNSs were
      characteristic to the Pestivirus genus, located in the V1 and V2 loci. The BVDV-1
      species shared a U-A pairing, a species-characteristic PNS, in position fifteen
      common to the V1 locus, and a G-C pairing in position five common to the V2 and
      V3 loci. Within the BVDV-1 species, 15 genotypes, BVDV-1a, BVDV-1b, BVDV-1c, BVDV
      1d, and the newly described from BVDV-1e to BVDV-1o were identified based on
      characteristic nucleotide base pairings. The nomenclature reflected the
      genotypes' level of divergence within the species. Genotypes BVDV-1l, BVDV-1m and
      BVDV-1o were borderline in the species. 

PMID- 24134937
TI  - Development of real-time PCR to detect oral vaccine-like poliovirus and its
      application to environmental surveillance.
AB  - In order to perform environmental surveillance to track oral poliovirus vaccine
      like poliovirus sensitively and conveniently, real-time PCR was developed and
      applied to a raw sewage concentrate. The real-time PCR method detected 0.01-0.1
      TCID50 of 3 serotypes of Sabin strain specifically. The method also detected the
      corresponding serotypes of oral poliovirus vaccine-like poliovirus specifically,
      but detected neither wild poliovirus, except Mahoney for type 1 and Saukett for
      type 3, nor other enteric viruses, as far as examined. When real-time PCR was
      applied to environmental surveillance, the overall agreement rates between real
      time PCR and the cell culture were 83.3% for all serotypes. Since real-time PCR
      has the advantages of rapid detection of viruses and minimum requirement of
      sampling volume as compared with ordinary cell culture, it is suitable to monitor
      oral poliovirus vaccine-like poliovirus in the environment, especially in areas
      where an oral vaccine is being replaced by an inactivated vaccine. 

PMID- 24134938
TI  - Characterisation of mouse monoclonal antibodies targeting linear epitopes on
      Chikungunya virus E2 glycoprotein.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne arbovirus which has recently re
      emerged globally and poses a major threat to public health. Infection leads to
      severe arthralgia, and disease management remains supportive in the absence of
      vaccines and anti-viral interventions. The high specificities of monoclonal
      antibodies (mAbs) have been exploited in immunodiagnostics and immunotherapy in
      recent decades. In this study, eight different clones of mAbs were generated and
      characterised. These mAbs targeted the linear epitopes on the CHIKV E2 envelope
      glycoprotein, which is the major target antigen during infection. All the mAbs
      showed binding activity against the purified CHIKV virion or recombinant E2 when
      analysed by immunofluorescence, ELISA and Western blot. The epitopes of each mAb
      were mapped by overlapping synthetic peptide-based ELISA. The epitopes are
      distributed at different functional domains of E2 glycoprotein, namely at domain
      A, junctions of beta-ribbons with domains A and B, and domain C. Alignment of mAb
      epitope sequences revealed that some are well-conserved within different
      genotypes of CHIKV, while some are identical to and likely to cross-react with
      the closely-related alphavirus O'nyong-nyong virus. These mAbs with their mapped
      epitopes are useful for the development of diagnostic or research tools,
      including immunofluorescence, ELISA and Western blot. 

PMID- 24134941
TI  - A sensitive nested real-time RT-PCR for the detection of Shuni virus.
AB  - Recently Shuni virus (SHUV) has been identified in clinical cases of neurological
      disease in horses in South Africa. Being that it was one of the less recognized
      orthobunyaviruses, with limited clinical descriptions of disease dating back to
      the 1960s and 1970s, SHUV-specific assays were never developed. In this study,
      the development of a nested real-time PCR assay is described for the detection of
      SHUV by means of melt-curve analysis using fluorescence resonance energy transfer
      (FRET) probe technology. The assay was validated against previously positive
      clinical specimens and a dilution series of controls. This assay was applied in
      the screening of 386 clinical specimens of horses with neurological signs. SHUV
      could be amplified from cell culture, blood and tissue specimens from horses with
      acute disease. This is a rapid and sensitive assay that may be implemented in
      both diagnostic and research laboratories. 

PMID- 24134940
TI  - Multiplex PCR for simultaneous detection and differentiation of sheeppox, goatpox
      and orf viruses from clinical samples of sheep and goats.
AB  - A multiplex polymerase chain reaction (mPCR) was developed and evaluated for
      detection of pox viral infections simultaneously using clinical samples from
      sheep and goats. Specific primers for three pox viruses of sheep and goats
      including sheeppox virus (SPPV), goatpox virus (GTPV) and orf virus (ORFV) were
      designed targeting conserved sequences of the DNA binding phosphoprotein (I3L)
      coding gene of Capripoxvirus (CaPV) and the DNA polymerase (E9L) gene of
      parapoxvirus for identification of these viruses. The mPCR assay was found to be
      sensitive for detecting as low as 350 pg of viral genomic DNA or 10(2) copies of
      standard plasmid of individual targets; and 10(3) copies of plasmid in a mixture
      of two or three viruses. The assay was specific for detecting one or more of the
      viruses in various combinations from clinical specimens. Two hundred and thirty
      five (n=235) clinical samples from sheep and goats received from different
      geographical regions of the country for diagnosis of pox infection were evaluated
      by developed uniplex and mPCR assays. The assay had improved diagnostic
      sensitivity and specificity over to in-use laboratory diagnostic methods and can
      be useful for clinical differential diagnosis of these infections in sheep and
      goats.

PMID- 24134939
TI  - Human bocavirus 1 infects commercially available primary human airway epithelium
      cultures productively.
AB  - Human bocavirus 1 (HBoV1), a human parvovirus, belongs to the genus Bocavirus of
      the Parvoviridae family. It causes wheezing in young children with acute
      respiratory tract infections. HBoV1 has been shown to infect polarized human
      airway epithelium (HAE) made in house, and induces airway epithelial damage. In
      this study, two commercially available HAE cultures, EpiAirway and MucilAir HAE,
      were examined for HBoV1 infection. Both HAE cultures support fully productive
      HBoV1 infection. Infected EpiAirway and MucilAir HAE cultures showed loss of
      cilia, disruption of the tight junction barrier, and a significant decrease in
      transepithelial electrical resistance. Notably, HBoV1 persistent infection was
      demonstrated by maintaining HBoV1-infected EpiAirway HAE for as long as 50 days.
      After 2 days post-infection, progeny virus was produced consistently daily at a
      level of over 2*10(8) viral genome copies per culture (0.6 cm(2)). This study is
      the first to use commercial sources of HAE cultures for HBoV1 infection. The
      availability of these cultures will enable a wide range of laboratories to study
      HBoV1 infection.

PMID- 24134942
TI  - Screening for H7N9 influenza A by matrix gene-based real-time reverse
      transcription PCR.
AB  - Rapid detection of novel influenza A strains, including H7N9, is pivotal to
      ensuring appropriate public health-based responses and real-time reverse
      transcription polymerase chain reaction (RT-PCR) methods are used typically for
      this purpose. However, the utility of such methods can be undermined by ongoing
      sequence variations, particularly when targeting the variable influenza A
      haemagglutinin (HA) and neuraminidase (NA) genes. This may often be a source of
      frustration for clinical laboratories that are implementing methods in
      preparation for potential pandemics as primers and probe targets may need to be
      checked regularly and updated. In this study, screening methods were developed
      for H7N9 influenza A strains based on the highly-conserved influenza A matrix
      gene. Three assays were developed and evaluated in parallel, and included two
      methods which simply involved inclusion of a single H7N9 probe sequence into an
      established influenza A and B multiplex RT-PCR (FluAB-PCR). The detection limits
      of the methods were compared using ten-fold dilutions of H7N9 RNA, and the
      specificity of the methods were tested using 32 influenza A RT-PCR-positive
      samples and a panel of 18 influenza A isolates, including representives of
      seasonal H3N2, seasonal H1N1, pandemic H1N1, H5N1, H5N3, H9N2 and H7N7. The
      detection limits of the three methods were the same, and no cross-reactions were
      observed with sH3N2, sH1N1, pH1N1 or H5N1. However, cross-reactions were observed
      with H5N3, H9N2 and H7N7. Overall, the results show that the methods are useful
      for front-line screening for H7N9. 

PMID- 24134943
TI  - A two-step real-time PCR assay for quantitation and genotyping of human
      parvovirus 4.
AB  - Human parvovirus 4 (PARV4) of the family Parvoviridae was discovered in a plasma
      sample of a patient with an undiagnosed acute infection in 2005. Currently, three
      PARV4 genotypes have been identified, however, with an unknown clinical
      significance. Interestingly, these genotypes seem to differ in epidemiology. In
      Northern Europe, USA and Asia, genotypes 1 and 2 have been found to occur mainly
      in persons with a history of injecting drug use or other parenteral exposure. In
      contrast, genotype 3 appears to be endemic in sub-Saharan Africa, where it
      infects children and adults without such risk behaviour. In this study, a novel
      straightforward and cost-efficient molecular assay for both quantitation and
      genotyping of PARV4 DNA was developed. The two-step method first applies a single
      probe pan-PARV4 qPCR for screening and quantitation of this relatively rare
      virus, and subsequently, only the positive samples undergo a real-time PCR-based
      multi-probe genotyping. The new qPCR-GT method is highly sensitive and specific
      regardless of the genotype, and thus being suitable for studying the clinical
      impact and occurrence of the different PARV4 genotypes. 

PMID- 24134944
TI  - Long-term maintenance of human fetal hepatocytes and prolonged susceptibility to
      HBV infection by co-culture with non-parenchymal cells.
AB  - Within a few days of being isolated, primary human hepatocytes undergo a rapid
      dedifferentiation process and lose susceptibility to hepatitis B virus (HBV)
      infection in vitro. This fact has limited their further application. In this
      study, a convenient and feasible method of preventing this dedifferentiation was
      established, by co-culturing human fetal hepatocytes with hepatic non-parenchymal
      cells to maintain the differentiation features of human fetal hepatocytes.
      Isolated hepatic cells were seeded at a low density, and cultured in dimethyl
      sulfoxide-free medium for a month to allow rapid proliferation of non-parenchymal
      cells. Subsequently, 2% dimethyl sulfoxide was added to induce formation of
      typical hepatic islands, in which hepatocytic features could be further
      maintained for up to an additional 3 months. These hepatic islands, formed of
      piled-up hepatocytes, were surrounded and invaded by non-parenchymal cells.
      Protein expression profiles showed that the human fetal hepatocytes underwent a
      rapid maturation process, and the hepatocytic features were well preserved. Most
      importantly, these human fetal hepatocytes still exhibited susceptibility to HBV
      infection after long-term maintenance, for as long as 10 weeks. This co-culture
      method has overcome the pre-existing disadvantages of primary human hepatocytes
      for virological studies, and provides a valuable approach to long-term
      maintenance of primary human hepatocytes for studies of HBV infection for
      prolonged periods. 

PMID- 24134945
TI  - MISIS: a bioinformatics tool to view and analyze maps of small RNAs derived from
      viruses and genomic loci generating multiple small RNAs.
AB  - In eukaryotes, diverse small RNA (sRNA) populations including miRNAs, siRNAs and
      piRNAs regulate gene expression and repress transposons, transgenes and viruses.
      Functional sRNAs are associated with effector proteins based on their size and
      nucleotide composition. The sRNA populations are currently analyzed by deep
      sequencing that generates millions of reads which are then mapped to a reference
      sequence or database. Here we developed a tool called MISIS to view and analyze
      sRNA maps of genomic loci and viruses which spawn multiple sRNAs. MISIS displays
      sRNA reads as a histogram where the x-axis indicates positions of the 5'- or 3'
      terminal nucleotide of sense and antisense sRNAs, respectively, along a given
      reference sequence or its selected region and the y-axis the number of reads
      starting (for sense sRNA) or ending (for antisense sRNA) at each position. Size
      classes of sRNAs can be visualized and compared separately or in combination.
      Thus, MISIS gives an overview of sRNA distribution along the reference sequence
      as well as detailed information on single sRNA species of different size-classes
      and abundances. MISIS reads standard BAM/SAM files outputted by mapping tools and
      generates table files containing counts of sRNA reads at each position of the
      reference sequence forward and reverse strand and for each of the chosen size
      classes of sRNAs. These table files can be used by other tools such as Excel for
      further quantitative analysis and visualization. MISIS is a Java standalone
      program. It is freely available along with the source code at the following
      website: http://www.fasteris.com/apps. 

PMID- 24134946
TI  - Is radiation dose reduction the right answer for HPV-positive head and neck
      cancer?
AB  - Patients with head and neck squamous cell carcinoma (HNC) related to human
      papillomavirus (HPV) represent a growing and distinct patient cohort with unique
      molecular and epidemiologic characteristics. These patients have markedly
      improved survival outcomes compared to those with traditional HNC, leading some
      to advocate for treatment dose reduction. In this article, we review ongoing
      clinical trials investigating several ways to reduce therapeutic intensity for
      patients with HPV-positive HNC, discuss the risks and benefits associated with
      these trials, and summarize the data underlying the advancement of dose reduction
      trials for patients with HPV-positive HNC. 

PMID- 24134948
TI  - Race and competing mortality in advanced head and neck cancer.
AB  - OBJECTIVES: Black patients with head and neck cancer (HNC) have poorer survival
      and disease control compared to non-black patients, but disparities in death from
      non-cancer causes (i.e., competing mortality) are less well-studied. MATERIALS
      AND METHODS: We conducted an analysis of 538 patients (169 black, 369 non-black)
      with stage III-IV HNC treated on one of six multi-institutional protocols between
      1993 and 2004 involving multi-agent chemoradiotherapy with or without surgery.
      Competing mortality was defined as death due to intercurrent comorbid disease,
      treatment-related morbidity, or unknown cause in the absence of disease
      recurrence, progression, or second malignancy. Cox proportional hazards and
      competing risks regression were used to estimate the effect of black race on
      competing mortality. RESULTS: Black race was associated with increased rates of
      comorbidity, smoking, heavy alcohol use, advanced tumor stage, and poorer
      performance status (p<.001 for all). Compared to non-black patients, black HNC
      patients had a higher 5 year cumulative incidence of disease progression (31.4%;
      95% CI, 24.4-38.5% vs 23.4%; 95% CI, 19.1-28.1%) and competing mortality (28.1%;
      95% CI, 21.2-35.3% vs 14.5%; 95% CI, 11.0-18.5%). When adjusting for age, male
      sex, body mass index, distance traveled, smoking and alcohol use, performance
      status, comorbidity, and tumor stage, the black race was associated with death
      from comorbid disease (Cox hazard ratio 2.13; 95% CI, 1.06-4.28, p=0.033).
      CONCLUSIONS: Black patients with advanced HNC are at increased risk of both
      disease progression and death from competing non-cancer mortality, particularly
      death from comorbid disease. Improved strategies to manage comorbid disease may
      increase the benefit of treatment intensification in black patients.

PMID- 24134947
TI  - The clinical impact of HPV tumor status upon head and neck squamous cell
      carcinomas.
AB  - Human papillomavirus (HPV) is etiologically responsible for a distinct subset of
      head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs)
      most commonly arise from the oropharynx and are responsible for the increasing
      incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV
      positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and
      tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher
      cumulative exposure to sexual behaviors as compared with HPV-negative OSCC
      patients. HPV-positive tumor status also significantly improves survival, and is
      indeed the single strongest prognostic factor for OSCC. The mechanisms that
      underlie the improved prognosis conferred by HPV-positive disease are unknown.
      The purpose of this review is to describe the clinical impact of HPV status in
      HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic
      profile and prognostic implications. 

PMID- 24134949
TI  - Severe iron deficiency is associated with a reduced conception rate in female
      rats.
AB  - BACKGROUND/AIMS: Iron deficiency is a global nutritional disorder, especially for
      pregnant women. There is a close relationship between deficiency in trace
      elements and unexplained infertility in females. However, the relationship
      between iron deficiency and unexplained infertility has not been determined. This
      study was designed to determine the effect of iron deficiency on conception in a
      rat model. METHODS: Female rats were randomly divided into two groups (n = 15
      each): an iron-deficiency group fed a low iron diet and a normal control group.
      Both groups of female rats were mated with healthy male rats after the iron
      deficiency model was established. RESULTS: Iron-deficient rats developed white
      skin and eyes, hair loss, and weight loss. Hemoglobin levels and red blood cell
      count were significantly lower than in controls, showing successful establishment
      of the iron-deficiency model. There was a significantly lower conception rate in
      the iron-deficiency group; there also appeared to be a disruption of estrus and a
      delay in conception in the iron-deficiency group. CONCLUSIONS: Severe iron
      deficiency has a significant influence on fertility, and may be an important
      factor in unexplained infertility. Further research on the role of iron in
      conception is warranted.

PMID- 24134950
TI  - The perimenopausal woman: endocrinology and management.
AB  - This review focuses on the endocrine and physiological features of the transition
      to menopause, known as the menopausal transition or the perimenopause. The
      updated 2011 Stages of Reproductive Aging workshop (STRAW) system is presented
      with a discussion of the new subdivisions within stages -3 (late reproductive
      age) and +1 (postmenopause) and incorporation of FSH and other biomarkers in the
      supportive criteria. Ovarian follicle reserve and ovarian follicle dynamics are
      also discussed in terms of the changes that occur with reproductive aging, and
      the dramatic effect these changes have on the hypothalamic-pituitary-gonadal
      feedback system. Topics include the disruption of normal ovulatory function and
      related hormone secretion patterns, abnormal uterine bleeding, and the changes
      that occur in bone and the cardiovascular system. The review concludes with a
      discussion of management strategies. This article is part of a Special Issue
      entitled 'Menopause'. 

PMID- 24134951
TI  - Neuroprotective effect through the cerebral sodium-glucose transporter on the
      development of ischemic damage in global ischemia.
AB  - Diabetes mellitus and impaired glucose metabolism are the most important risk
      factors for stroke. We recently demonstrated that cerebral ischemic stress causes
      hyperglycemia (i.e., post-ischemic hyperglycemia) and may worsen ischemic
      neuronal damage in a mouse model of focal ischemia. However, the detailed
      mechanisms are still unknown. The sodium-glucose transporter (SGLT) generates
      inward currents in the process of transporting glucose into cells, resulting in
      depolarization and increased excitability, which is well known to be caused by
      cerebral ischemia. Hence, we focused on the role of SGLT on the development of
      neuronal damage using a global ischemic model. Male ddY mice were subjected to
      30min of bilateral carotid artery occlusion (BCAO). The neuronal damage was
      estimated by histological analysis using HE staining on day 3 after BCAO.
      Intraperitoneal (i.p.) administration of phlorizin (a specific and competitive
      inhibitor of SGLT, 200mg/kg immediately after reperfusion) suppressed the
      development of post-ischemic hyperglycemia on day 1 after BCAO. In contrast,
      intracerebroventricular (i.c.v.) administration of phlorizin (40MUg/mouse
      immediately and 6h after reperfusion) had no effect on day 1 after BCAO.
      Interestingly, the development of ischemic neuronal damage was significantly
      suppressed by i.p. and i.c.v. administration of phlorizin on day 3 after BCAO. In
      addition, BCAO-induced spasticity was significantly suppressed by PHZ
      (40MUg/mouse, i.c.v.) from using gait analysis. Our results indicated that
      cerebral SGLT was involved in the development of ischemic neuronal damage in
      global ischemia. 

PMID- 24134953
TI  - The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25
      and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive
      impairment.
AB  - Changes of synaptic proteins in highlighted brain regions and decreased serum
      thyroid hormones (THs) have been implied in age-related learning and memory
      decline. Previously, we showed significant pairwise correlations among markedly
      impaired spatial learning and memory ability, decreased serum free
      triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old
      Kunming mice. However, whether these changes and the correlations occur in middle
      age mice remains unclear. Since this age is one of the best stages to study age
      related cognitive decline, we explored the spatial learning and memory ability,
      serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle
      aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19
      mice aged 6 months and 16 mice aged 12 months) were measured with a radial six
      arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by
      Western blotting and the serum THs were detected by radioimmunoassay. The results
      showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal
      (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both
      learning and memory phases of the RAWM. The Pearson's correlation test showed
      that the DH SANP-25 and Munc18-1 levels were positively correlated with the
      number of errors and latency in learning phases of the RAWM. Meanwhile, the DH
      SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These
      results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels
      might be involved in the spatial learning ability decline in the middle-aged
      mice. 

PMID- 24134952
TI  - Novel song-stimulated dendritic spine formation and Arc/Arg3.1 expression in
      zebra finch auditory telencephalon are disrupted by cannabinoid agonism.
AB  - Cannabinoids are well-established to alter processes of sensory perception;
      however neurophysiological mechanisms responsible remain unclear. Arc, an
      immediate-early gene (IEG) product involved in dendritic spine dynamics and
      necessary for plasticity changes such as long-term potentiation, is rapidly
      induced within zebra finch caudal medial nidopallium (NCM) following novel song
      exposure, a response that habituates after repeated stimuli. Arc appears unique
      in its rapid postsynaptic dendritic expression following excitatory input.
      Previously, we found that vocal development-altering cannabinoid treatments are
      associated with elevated dendritic spine densities in motor-(HVC) and learning
      related (Area X) song regions of zebra finch telencephalon. Given Arc's dendritic
      morphological role, we hypothesized that cannabinoid-altered spine densities may
      involve Arc-related signaling. To test this, we examined the ability of the
      cannabinoid agonist WIN55212-2 (WIN) to (1) acutely disrupt song-induced Arc
      expression, (2) interfere with habituation to auditory stimuli, and (3) alter
      dendritic spine densities in auditory regions. We found that WIN (3mg/kg) acutely
      reduced Arc expression within both NCM and Field L2 in an antagonist-reversible
      manner. WIN did not alter Arc expression in thalamic auditory relay nucleus
      ovoidalis (Ov), suggesting that cannabinoid signaling selectively alters
      responses to auditory stimulation. Novel song stimulation rapidly increased
      dendritic spine densities within auditory telencephalon, an effect blocked by WIN
      pretreatments. Taken together, cannabinoid inhibition of both Arc induction and
      its habituation to repeated stimuli, combined with prevention of rapid increases
      in dendritic spine densities, implicates cannabinoid signaling in modulation of
      physiological processes important to auditory responsiveness and memory. 

PMID- 24134954
TI  - Chronic Akt1 deficiency attenuates adverse remodeling and enhances angiogenesis
      after myocardial infarction.
AB  - BACKGROUND: Akt1 is a key signaling molecule in multiple cell types, including
      endothelial cells. Accordingly, Akt1 was proposed as a therapeutic target for
      ischemic injury in the context of myocardial infarction (MI). The aim of this
      study was to use multimodal in vivo imaging to investigate the impact of systemic
      Akt1 deficiency on cardiac function and angiogenesis before and after MI. METHODS
      AND RESULTS: In vivo cardiac MRI was performed before and at days 1, 8, 15, and
      29 to 30 after MI induction for wild-type, heterozygous, and Akt1-deficient mice.
      Noninfarcted hearts were imaged using ex vivo stereomicroscopy and microcomputed
      tomography. Histological examination was performed for noninfarcted hearts and
      for hearts at days 8 and 29 to 30 after MI. MRI revealed mildly decreased
      baseline cardiac function in Akt1 null mice, whereas ex vivo stereomicroscopy and
      microcomputed tomography revealed substantially reduced coronary
      macrovasculature. After MI, Akt1(-/-) mice demonstrated significantly attenuated
      ventricular remodeling and a smaller decrease in ejection fraction. At 8 days
      after MI, a larger functional capillary network at the remote and border zone,
      accompanied by reduced scar extension, preserved cardiac function, and enhanced
      border zone wall thickening, was observed in Akt1(-/-) mice when compared with
      littermate controls. CONCLUSIONS: Using multimodal imaging to probe the role of
      Akt1 in cardiac function and remodeling after MI, this study revealed reduced
      adverse remodeling in Akt1-deficient mice after MI. Augmented myocardial
      angiogenesis coupled with a more functional myocardial capillary network may
      facilitate revascularization and therefore be responsible for preservation of
      infarcted myocardium.

PMID- 24134955
TI  - Assessment of mitral valve area during percutaneous mitral valve repair using the
      MitraClip system: comparison of different echocardiographic methods.
AB  - BACKGROUND: Quantification of the mitral valve area (MVA) is important to guide
      percutaneous mitral valve repair using the MitraClip system. However, little is
      known about how to best assess MVA in this specific situation. METHODS AND
      RESULTS: Immediately before and after MitraClip implantation, comprehensive 3
      dimensional (3D) transesophageal echocardiography data were acquired for MVA
      assessment by the pressure half-time method and by two 3D quantification methods
      (mitral valve quantification software and 3D quantification software). In
      addition, transmitral gradients by continuous-wave Doppler (dPmeanCW) were
      measured to indirectly assess MVA. Data are given as median (interquartile
      range). Thirty-three patients (39% women) with a median age of 77.1 years (12.4
      years) were studied. Before intervention, the median MVAs by the pressure half
      time method, mitral valve quantification software, and 3D quantification software
      were 4.4 cm(2) (2.0 cm(2)), 4.7 cm(2) (2.4 cm(2)), and 6.2 cm(2) (2.4 cm(2)),
      respectively (P<0.001). After intervention, MVA was reduced to 1.9 cm(2) (0.7
      cm(2)), 2.1 cm(2) (1.1 cm(2)), and 2.8 cm(2) (1.1 cm(2)), respectively (P=0.001).
      The median values for dPmeanCW before and after intervention were 1.0 mm Hg (1.0
      mm Hg) and 3.0 mm Hg (3.0 mm Hg; P<0.001), respectively. At discharge, the median
      dPmeanCW was 4.0 mm Hg (3.0 mm Hg). In multivariate regression analyses including
      body surface area, the 3 different MVA methods, and dPmeanCW, a post-dPmeanCW >=5
      mm Hg was the best independent predictor of an elevated transmitral gradient at
      discharge. CONCLUSIONS: Transmitral gradients by continuous-wave Doppler are
      quick, feasible in all patients, and superior to direct peri-interventional
      assessment of MVA. A postinterventional transmitral gradient by continuous-wave
      Doppler of >=5 mm Hg best predicted elevated transmitral gradients at discharge.

PMID- 24134957
TI  - Overexpression of steroid receptor coactivator-3 in bone cancers: an in vivo
      immunohistochemical study with tissue microarray.
AB  - Bone tissue is steroid-responsive and profoundly regulated by steroids and/or
      their receptors. Bone cancers (either primary or metastatic) belong to the most
      dangerous tumors. Previous studies have demonstrated overexpression of steroid
      receptor coactivator-3 (SRC-3) in many cancers, such as breast cancer, prostate
      cancer, thyroid cancer, functioning in the regulation of cancer cell
      proliferation, invasion, and metastasis. However, so far, the expression and
      function of SRC-3 in bone cancers have not yet been clarified. In this study,
      nickel-intensified immunohistochemistry was conducted using a commercial tissue
      microarray (with 94 cases of bone cancer tissue and 10 normal bone tissues), and
      the 4-scoring system was employed to evaluate the expression levels of SRC-3
      immunoreactivity. The results showed that in normal bone tissue, levels of SRC-3
      are almost negative (score=0), the total positivity (score=1-3) of SRC-3
      immunoreactivities in bone cancers was 74.47%. There were no significant
      differences in gender, status (malignant or benign) or (mean) age (p>0.05). The
      percentage of positivity was 77.78% in osteogenic tumors, 58.82% in cartilage
      tumors, 70% in giant cell tumors, 100% in hematopoietic tumors, 77.78% in
      miscellaneous lesions, and 75% in miscellaneous tumors. Age related differences
      of SRC-3 immunoreactivities were detected in cartilage tumors and giant cell
      tumors (p<0.05). The above results clearly demonstrated a high frequency of
      overexpression of SRC-3 immunoreactivities in different bone cancers, indicating
      its potential roles in the prognosis and treatment of these cancers.

PMID- 24134956
TI  - Implementation of personalized self-management support using the self-management
      screening questionnaire SeMaS; a study protocol for a cluster randomized trial.
AB  - BACKGROUND: The number of patients with one or more chronic diseases is rising.
      In several standards of care there is a focus on enhancing self-management. We
      applied the concept of personalization on self-management support and developed a
      self-management screening questionnaire (SeMaS). The main research objective is
      to assess the effectiveness of the SeMaS questionnaire and subsequent
      personalized self-management on patients' self-management behaviors.
      METHODS/DESIGN: A cluster randomized controlled trial will be set up in 15
      general practices in the Netherlands. The practices are all group practices, and
      member of one care group. The practices will be assigned to the control or
      intervention arms by stratified randomization. The strata are determined by the
      participation of the practice nurses in a course for behavioral change, and the
      nurse's workload. Patients can be included if they are over 18 years of age, have
      at least one chronic condition and have a checkup appointment with the practice
      nurse in the inclusion period. The intervention consists of screening patients
      with the SeMaS questionnaire, producing a graphic profile with the abilities or
      barriers for self-management. Patients will receive tailored feedback. Practice
      nurses are trained in using the profile to enhance self-management of the patient
      and provide personalized self-management support. The use of individual care
      plans and self-management interventions is stimulated. In the control arm
      patients will receive care as usual. Patients of both trial arms will be asked to
      fill in the SeMaS questionnaire and additional questionnaires at inclusion and
      after 6 months. The primary outcome is the difference in the level of patient
      activation (PAM-13) between baseline and 6 months. Secondary outcomes include
      patient measures for lifestyle factors (exercise, diet, smoking), and process
      measures from medical record data analysis. DISCUSSION: This manuscript presents
      the protocol for a cluster randomized clinical trial of personalized self
      management support using the SeMaS questionnaire in chronically ill patients in
      primary care. By carrying out this study, scientific evidence is built for the
      effectiveness of personalized self-management support. TRIAL REGISTRATION: The
      Netherlands National Trial Register: NTR3960.

PMID- 24134958
TI  - Applications of justification and optimization in medical imaging: examples of
      clinical guidance for computed tomography use in emergency medicine.
AB  - Availability, reliability, and technical improvements have led to continued
      expansion of computed tomography (CT) imaging. During a CT scan, there is
      substantially more exposure to ionizing radiation than with conventional
      radiography. This has led to questions and critical conclusions about whether the
      continuous growth of CT scans should be subjected to review and potentially
      restraints or, at a minimum, closer investigation. This is particularly pertinent
      to populations in emergency departments, such as children and patients who
      receive repeated CT scans for benign diagnoses. During the last several decades,
      among national medical specialty organizations, the American College of Emergency
      Physicians and the American College of Radiology have each formed membership
      working groups to consider value, access, and expedience and to promote broad
      acceptance of CT protocols and procedures within their disciplines. Those efforts
      have had positive effects on the use criteria for CT by other physician groups,
      health insurance carriers, regulators, and legislators. 

PMID- 24134959
TI  - Investigation of the self-reported health and health-related behaviours of
      Victorian mothers of school-aged children.
AB  - Lifestyle may influence many health-related issues currently facing Australian
      women. The extent to which women with school-aged children attend to their own
      health is unknown and the associations between health behaviours and health
      status requires investigation. This study aimed to investigate the prevalence of
      health behaviours (alcohol consumption, health-promoting activities) and their
      impact on self-reported health (weight, sleep quality, mental health) among
      mothers of school-aged children in Victoria. Mail-out survey design (n=263)
      including the Depression Anxiety Stress Scale (DASS) and Health Promoting
      Activities Scale was used to explore issues. The results indicated that
      substantial numbers of mothers reported moderate to extreme DASS scores:
      depression (n=45, 17%); anxiety (n=41, 15.6%); stress (n=57, 21.7%). The majority
      participated in physical activity less often than daily. High rates of daily
      alcohol use (20%) and poor sleep quality were reported. Nearly one-half (n=114,
      46%) of the sample were overweight or obese and also reported poorer mental
      health than other women in the sample (P<0.001). Significant associations were
      detected between maternal weight, mental health and participation in health
      promoting activities. The findings indicate that there is a need for increased
      health education and services for women with school-aged children. Direct
      services and population-based health promotion strategies may be required to
      address healthy lifestyle issues and educate mothers about the possible health
      legacy of poor health behaviours. 

PMID- 24134960
TI  - Improved age control on early Homo fossils from the upper Burgi Member at Koobi
      Fora, Kenya.
AB  - To address questions regarding the evolutionary origin, radiation and dispersal
      of the genus Homo, it is crucial to be able to place the occurrence of hominin
      fossils in a high-resolution chronological framework. The period around 2 Ma
      (millions of years ago) in eastern Africa is of particular interest as it is at
      this time that a more substantial fossil record of the genus Homo is first found.
      Here we combine magnetostratigraphy and strontium (Sr) isotope stratigraphy to
      improve age control on hominin-bearing upper Burgi (UBU) deposits in Areas 105
      and 131 on the Karari Ridge in the eastern Turkana Basin (Kenya). We identify the
      base of the Olduvai subchron (bC2n) plus a short isolated interval of
      consistently normal polarity that we interpret to be the Pre-Olduvai event.
      Combined with precession-forced (~20 kyr [thousands of years]) wet-dry climate
      cycles resolved by Sr isotope ratios, the magnetostratigraphic data allow us to
      construct an age model for the UBU deposits. We provide detailed age constraints
      for 15 hominin fossils from Area 131, showing that key specimens such as cranium
      KNM-ER 1470, partial face KNM-ER 62000 and mandibles KNM-ER 1482, KNM-ER 1801,
      and KNM-ER 1802 can be constrained between 1.945 +/- 0.004 and 2.058 +/- 0.034
      Ma, and thus older than previously estimated. The new ages are consistent with a
      temporal overlap of two species of early Homo that can be distinguished by their
      facial morphology. Further, our results show that in this time interval, hominins
      occurred throughout the wet-dry climate cycles, supporting the hypothesis that
      the lacustrine Turkana Basin was a refugium during regionally dry periods. By
      establishing the observed first appearance datum of a marine-derived stingray in
      UBU deposits at 2.058 +/- 0.034 Ma, we show that at this time the Turkana Basin
      was hydrographically connected to the Indian Ocean, facilitating dispersal of
      fauna between these areas. From a biogeographical perspective, we propose that
      the Indian Ocean coastal strip should be considered as a possible source area for
      one or more of the multiple Homo species in the Turkana Basin from over 2 Ma
      onwards.

PMID- 24134961
TI  - Primate brains, the 'island rule' and the evolution of Homo floresiensis.
AB  - The taxonomic status of the small bodied hominin, Homo floresiensis, remains
      controversial. One contentious aspect of the debate concerns the small brain size
      estimated for specimen LB1 (Liang Bua 1). Based on intraspecific mammalian
      allometric relationships between brain and body size, it has been argued that the
      brain of LB1 is too small for its body mass and is therefore likely to be
      pathological. The relevance and general applicability of these scaling rules has,
      however, been challenged, and it is not known whether highly encephalized
      primates adapt to insular habitats in a consistent manner. Here, an analysis of
      brain and body size evolution in seven extant insular primates reveals that
      although insular primates follow the 'island rule', having consistently reduced
      body masses compared with their mainland relatives, neither brain mass nor
      relative brain size follow similar patterns, contrary to expectations that
      energetic constraints will favour decreased relative brain size. Brain:body
      scaling relationships previously used to assess the plausibility of dwarfism in
      H. floresiensis tend to underestimate body masses of insular primates. In
      contrast, under a number of phylogenetic scenarios, the evolution of brain and
      body mass in H. floresiensis is consistent with patterns observed in other
      insular primates. 

PMID- 24134963
TI  - Abstracts of the 6th International Alkaline Phosphatase and Hypophosphatasia
      Symposium, May 16-19, 2012, Huningue, France.

PMID- 24134962
TI  - Virologic and immunologic effectiveness at 48 weeks of darunavir-ritonavir-based
      regimens in treatment-experienced persons living with HIV-1 infection in clinical
      practice: a multicenter Brazilian cohort.
AB  - INTRODUCTION: Published data addressing the effectiveness of darunavir-ritonavir
      (DRV/r)-based therapy for multiexperienced patients in developing countries are
      scarce. This study evaluated the 48-week virologic and immunologic effectiveness
      of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV
      1-infected adults in Brazil. MATERIALS AND METHODS: A multicenter retrospective
      cohort study was carried out with multidrug-experienced adults who were on a
      failing antiretroviral therapy and started a DRV/r-based salvage therapy between
      2008 and 2010. The primary effectiveness end point was the proportion of patients
      with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). RESULTS: At
      48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of
      108 CD4 cells/mm(3). Higher baseline viral load, lower baseline CD4 count,
      younger age, and 3 or more DRV/r-associated resistance mutations were
      significantly predictive of virologic failure. Concomitant use of raltegravir was
      strongly associated with virologic success. CONCLUSION: The use of DRV/r-based
      regimens for salvage therapy is an effective strategy in the clinical care
      setting of a developing country.

PMID- 24134999
TI  - Bioelectrocatalytic reduction of oxygen at gold nanoparticles modified with
      laccase.
AB  - To characterise bioelectrocatalytic oxygen reduction at gold nanoparticles
      (AuNPs) modified with Trametes hirsuta laccase (ThLc) combined electrochemical
      and quartz crystal microbalance measurements have been used. The electrodes with
      different degrees of AuNP-monolayer coverage, theta, have been studied. In every
      case of theta close to theoretically possible 44 ThLc molecules adsorbed at 22nm
      diameter AuNP. The bioelectrocatalytic current was recalculated down to the
      current at a single AuNP. Unexpectedly, the current at a single AuNP was higher
      when theta was higher. The maximum current reached at a single AuNP was 31.10(
      18)A which corresponds to the enzyme turnover (kcat) 13s(-1). This rate is lower
      than the homogeneous ThLc turnover (190s(-1)) suggesting partial denaturation of
      ThLc upon adsorption or that some ThLc are not in DET contact with the electrode
      surface. 

PMID- 24135000
TI  - Effect of chemical and hydrostatic pressures on structural and magnetic
      properties of rare-earth orthoferrites: a first-principles study.
AB  - The dependence of structural and magnetic properties of rare-earth orthoferrites
      (in their Pbnm ground state) on the rare-earth ionic radius is systematically
      investigated from first principles. The effects of this 'chemical pressure' on
      lattice constants, Fe-O bond lengths, Fe-O-Fe bond angles and Fe-O bond length
      splittings are all well reproduced by these ab initio calculations. The
      simulations also offer novel predictions (on tiltings of FeO6 octahedra, cation
      antipolar displacements and weak magnetization) to be experimentally checked. In
      particular, the weak ferromagnetic moment of rare-earth orthoferrites is
      predicted to be a linear function of the rare-earth ionic radius. Finally, the
      effects of applying hydrostatic pressure on structural and magnetic behavior of
      SmFeO3 is also studied. It is found that, unlike previously assumed, hydrostatic
      pressure typically generates changes in physical properties that are
      quantitatively and even qualitatively different from those associated with the
      chemical pressure. 

PMID- 24135001
TI  - Carbon plate shows even distribution of stress, decreases screw loosening, and
      increases recovery of preoperative daily feed intake amount in a rabbit model of
      mandibular continuity defects.
AB  - INTRODUCTION: The aim of this study was to compare a carbon plate (CP) and a
      titanium mandibular reconstruction plate (TMRP) in finite element analysis and an
      animal model. MATERIALS AND METHODS: Twelve rabbits were used for this
      experiment. After a mandible continuity defect was created, either a CP or a TMRP
      was used for mandibular reconstruction. Postoperatively, daily feed intake amount
      (DFIA) was measured for 4 weeks. Radiographic images were also acquired to
      evaluate screw loosening. For the analysis of the stress distribution, a simple
      continuity defect model was used, and finite element analysis was performed.
      RESULTS: The CP group had 0.80 +/- 0.45 lost screws in an animal during the 4
      weeks postoperative observation; however, the TMRP group had 1.86 +/- 0.69 lost
      screws (p = 0.014). Overall, the 5 out of 5 of rabbits in the CP group and 3 out
      of 7 in the TMRP group exhibited preoperative levels of DFIA during the 4 week
      observation (p = 0.038). The finite element analysis showed that the stress was
      more evenly distributed in the CP than in the TMRP model. CONCLUSIONS: The CP
      group showed decreased screw loosening and increased recovery of preoperative
      DFIA compared to the TMRP group in a rabbit model of mandibular continuity
      defects. Perfect adaptation of CP during the operation could not be achieved in
      spite of reshaping to the mandibular curvature. This disadvantage of the CP
      system can be overcome by the prefabricated technique using a prototype model.

PMID- 24135002
TI  - Finding Ernst Mayr's Plato.
AB  - Many biologists have accepted Ernst Mayr's claim that evolutionary biology
      undermined an essentialist or typological view of species that had its roots in
      Platonic philosophy. However, Mayr has been accused of failing to support with
      textual evidence his attributions to Plato of these sorts of views about biology.
      Contemporary work in history and philosophy of biology often seems to take
      onboard Mayr's account of Plato's view of species. This paper seeks to provide a
      critical account of putative inconsistencies between an evolutionary view of
      species and Platonic philosophy with renewed attention to the Platonic texts in
      light of recent Plato scholarship; I argue that claims that Plato held an
      essentialist view of species inconsistent with evolutionary biology are
      inadequately supported by textual evidence. If Mayr's essentialist thesis fails,
      one might think that the intuition that Platonic philosophy is in tension with
      Darwinian evolution could nonetheless be accounted for by Plato's apparent
      privileging of a certain sort of teleological explanation, a thesis that Mayr
      suggests in his 1959 paper on Louis Agassiz. However, this thesis also faces
      difficulties. Ernst Mayr's Plato is more likely to be found in the writings of
      anti-evolutionary 19th century biologists like Mayr's frequent target, Agassiz,
      than in a cautious reading of the Platonic dialogues themselves. Interlocutors in
      discussions of the history of biological thought and classificatory methods in
      biology should be cautious in ascribing views about biology to Plato and using
      terms like "Platonic essentialism." 

PMID- 24135003
TI  - Tony Pawson: Modular protein domains and the links to intracellular signaling.

PMID- 24135004
TI  - Highly correlated hedonic and eudaimonic well-being thwart genomic analysis.

PMID- 24135005
TI  - Is a Stern and diffuse layer model appropriate to ionic liquids at surfaces?

PMID- 24135006
TI  - The anti-dyskinetic effect of dopamine receptor blockade is enhanced in
      parkinsonian rats following dopamine neuron transplantation.
AB  - Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA)
      cell transplantation in parkinsonian patients. We have recently shown that DA D2
      receptor blockade produces striking blockade of dyskinesia induced by amphetamine
      in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to
      investigate whether blockade of DA D1 receptors could produce similar outcome,
      and to see whether the effect of these treatments in grafted rats was specific
      for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced
      dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons
      into the DA-denervated striatum. Beginning at 20weeks after transplantation rats
      were subjected to pharmacological treatments with either L-DOPA (6mg/kg) or
      amphetamine (1.5mg/kg) alone, or in combination with the D1 receptor antagonist
      SCH23390, the D2 receptor antagonist eticlopride, and the 5-HT1A agonist/D2
      receptor antagonist buspirone. Grafted rats developed severe GID, while LID was
      reduced. Both eticlopride and SCH23390 produced near-complete suppression of GID
      already at very low doses (0.015 and 0.1mg/kg, respectively). Buspirone induced
      similar suppression at a dose as low as 0.3mg/kg, which is far lower than the
      dose known to affect LID in non-grafted dyskinetic rats. In agreement with our
      previous results, the effect of buspirone was independent from 5-HT1A receptor
      activation, as it was not counteracted by the selective 5-HT1A antagonist
      WAY100635, but likely due to D2 receptor blockade. Most interestingly, the same
      doses of eticlopride, SCH23390 and buspirone were found to suppress LID in
      grafted but not in control dyskinetic rats. Taken together, these data
      demonstrate that the DA cell grafts strikingly exacerbate the effect of DA D1 and
      D2 receptor blockade against both GID and LID, and suggest that the anti-GID
      effect of buspirone seen in patients may also be due to blockade of DA D2
      receptors. 

PMID- 24135007
TI  - Resolving pathobiological mechanisms relating to Huntington disease: gait,
      balance, and involuntary movements in mice with targeted ablation of striatal D1
      dopamine receptor cells.
AB  - Progressive cell loss is observed in the striatum, cerebral cortex, thalamus,
      hypothalamus, subthalamic nucleus and hippocampus in Huntington disease. In the
      striatum, dopamine-responsive medium spiny neurons are preferentially lost.
      Clinical features include involuntary movements, gait and orofacial impairments
      in addition to cognitive deficits and psychosis, anxiety and mood disorders. We
      utilized the Cre-LoxP system to generate mutant mice with selective postnatal
      ablation of D1 dopamine receptor-expressing striatal neurons to determine which
      elements of the complex Huntington disease phenotype relate to loss of this
      neuronal subpopulation. Mutant mice had reduced body weight, locomotor slowing,
      reduced rearing, ataxia, a short stride length wide-based erratic gait,
      impairment in orofacial movements and displayed haloperidol-suppressible tic-like
      movements. The mutation was associated with an anxiolytic profile. Mutant mice
      had significant striatal-specific atrophy and astrogliosis. D1-expressing cell
      number was reduced throughout the rostrocaudal extent of the dorsal striatum
      consistent with partial destruction of the striatonigral pathway. Additional
      striatal changes included up-regulated D2 and enkephalin mRNA, and an increased
      density of D2 and preproenkephalin-expressing projection neurons, and striatal
      neuropeptide Y and cholinergic interneurons. These data suggest that striatal D1
      cell-ablation alone may account for the involuntary movements and locomotor,
      balance and orofacial deficits seen not only in HD but also in HD phenocopy
      syndromes with striatal atrophy. Therapeutic strategies would therefore need to
      target striatal D1 cells to ameliorate deficits especially when the clinical
      presentation is dominated by a bradykinetic/ataxic phenotype with involuntary
      movements. 

PMID- 24135008
TI  - Interferon-beta1a protects neurons against mitochondrial toxicity via modulation
      of STAT1 signaling: electrophysiological evidence.
AB  - Multiple sclerosis, one of the main causes of non-traumatic neurological
      disability in young adults, is an inflammatory and neurodegenerative disorder of
      the central nervous system. Although the pathogenesis of neuroaxonal damage
      occurring during the course of the disease is still largely unknown, there is
      accumulating evidence highlighting the potential role of mitochondria in multiple
      sclerosis-associated neuronal degeneration. The aim of the present study was to
      investigate, by utilizing electrophysiological techniques in brain striatal
      slices, the potential protective effects of interferon-beta1a, one of the most
      widely used medication for multiple sclerosis, against acute neuronal dysfunction
      induced by mitochondrial toxins. Interferon-beta1a was found to exert a dose
      dependent protective effect against the progressive loss of striatal field
      potential amplitude induced by the mitochondrial complex I inhibitor rotenone.
      Interferon-beta1a also reduced the generation of the rotenone-induced inward
      current in striatal spiny neurons. Conversely, interferon-beta1a did not
      influence the electrophysiological effects of the mitochondrial complex II
      inhibitor 3-nitropropionic acid. The protective effect of interferon-beta1a
      against mitochondrial complex I inhibition was found to be dependent on the
      activation of STAT1 signaling. Conversely, endogenous dopamine depletion and the
      modulation of the p38 MAPK and mTOR pathways did not influence the effects of
      interferon-beta1a. During experimental autoimmune encephalomyelitis (EAE)
      striatal rotenone toxicity was enhanced but the protective effect of interferon
      beta1a was still evident. These results support future studies investigating the
      role played by specific intracellular signaling pathways in mediating the
      potential link among inflammation, mitochondrial impairment and neuroaxonal
      degeneration in multiple sclerosis. 

PMID- 24135009
TI  - Time to get serious about improving the safety of oral chemotherapy.

PMID- 24135010
TI  - American Society of Clinical Oncology/Oncology Nursing Society chemotherapy
      safety standards.

PMID- 24135011
TI  - Case-control association analysis of dopamine receptor polymorphisms in alcohol
      dependence: a pilot study in Indian males.
AB  - BACKGROUND: Brain imaging studies and knock-out animal models have derived
      substantial abetment for dopamine receptor (DR) subtypes as potential candidates
      in susceptibility to addictive disorders, including alcohol dependence (AD).
      Various association studies that compared the frequencies of alleles of the
      dopamine D1, D2, D3 and D4 receptor genes between alcohol dependent and control
      subjects have produced suggestive results, though some of them are discordant in
      nature. In the absence of genetic data from Indian population, we evaluated
      genetic association of three polymorphisms namely rs4532 in DRD1, rs6280 in DRD3
      and 120 bp duplication in 1.2 kb upstream region of DRD4 with AD. METHODS: A
      total of 90 cases (alcohol dependent males) and 122 age and ethnicity matched
      healthy male controls were recruited in the study by following DSM-IV criteria.
      Three polymorphisms, namely rs4532 in DRD1, rs6280 in DRD3 and 120 bp duplication
      in 1.2 kb upstream region of DRD4 were selected (based on minor allele frequency
      and available literature) for genotyping by PCR-RFLP/LP method. Allele and
      genotype frequencies of these genetic markers were compared using Pearson's chi2
      test followed by risk assessment using odds ratio. Statistical analysis of
      clinical parameters such as AUDIT scores of case subjects was also performed.
      RESULTS: Statistically significant associations of polymorphisms in DRD1 and DRD4
      with alcoholism were found. CONCLUSIONS: Our results underscore that genetic
      variations in dopamine receptors D1 and D4 may influence genetic predisposition
      to alcoholism. Unavailability of comparative data from Indian population and
      small sample size necessitate replication of results in an independent cohort.

PMID- 24135012
TI  - Fosphenytoin for seizure prevention in childhood coma in Africa: a randomized
      clinical trial.
AB  - PURPOSE: We conducted a double-blind trial to determine whether a single
      intramuscular injection of fosphenytoin prevents seizures and neurologic sequelae
      in children with acute coma. METHODS: We conducted this study at Kilifi District
      Hospital in coastal Kenya and Kondele Children's Hospital in western Kenya. We
      recruited children (age, 9 months to 13 years) with acute nontraumatic coma. We
      administered fosphenytoin (20 phenytoin equivalents/kg) or placebo and examined
      the prevalence and frequency of clinical seizures and occurrence of
      neurocognitive sequelae. RESULTS: We recruited 173 children (median age, 2.6
      [interquartile range, 1.7-3.7] years) into the study; 110 had cerebral malaria, 8
      had bacterial meningitis, and 55 had encephalopathies of unknown etiology. Eighty
      five children received fosphenytoin and 88 received placebo. Thirty-three (38%)
      children who received fosphenytoin had at least 1 seizure compared with 32 (36%)
      who received placebo (P = .733). Eighteen (21%) and 15 (17%) children died in the
      fosphenytoin and placebo arms, respectively (P = .489). At 3 months after
      discharge, 6 (10%) children in the fosphenytoin arm had neurologic sequelae
      compared with 6 (10%) in the placebo arm (P = .952). CONCLUSION: A single
      intramuscular injection of fosphenytoin (20 phenytoin equivalents/kg) does not
      prevent seizures or neurologic deficits in childhood acute nontraumatic coma.

PMID- 24135013
TI  - Selenium supplementation in critically ill patients: a systematic review and meta
      analysis.
AB  - PURPOSE: The oxidative stress is recognized as a constant feature in critical
      illness. Nevertheless, the use of antioxidant therapy remains controversial. We
      tried to demonstrate that intravenous selenium supplementation could promote
      antioxidant status and help protect against infection and organ failure,
      improving outcome in critically ill patients. MATERIALS AND METHODS: We conducted
      a systematic review and meta-analysis of randomized controlled trials (RCTs)
      comparing the exogenous supplementation of selenium versus standard therapy
      without any adjuvant in critically ill adults. RESULTS: Nine RCTs met inclusion
      criteria. Selenium supplementation was associated with a reduction in 28-day
      mortality of borderline statistical significance (risk ratio = 0.84, 95%
      confidence interval 0.71-0.99, P = .04). The analysis of pre-defined subgroups
      detected no significant effects regarding the supplementation with doses of
      selenium <= 500 MUg/d, administration of a load dose with a bolus and duration of
      treatment. Only 2 studies analyzed 6-month mortality and could not show a
      difference. No effects could be demonstrated on hospital length of stay,
      pulmonary infections, or renal failure. CONCLUSIONS: The use of high-dose
      selenium might be associated with a beneficial effect on 28-day mortality in
      critically ill patients. Nevertheless, the use of selenium as adjuvant therapy
      needs further evaluations.

PMID- 24135014
TI  - Echocardiography in the use of noninvasive hemodynamic monitoring.
AB  - Invasive pulmonary artery catheter measurements are the standard method for
      assessment of hemodynamic evaluation at the present time. However, this invasive
      approach is associated with an increase in patient morbidity and without evidence
      of a reduction in mortality. Doppler echocardiography is a noninvasive method
      that provides robust data regarding patients' hemodynamic indices. Several
      parameters are available for noninvasive hemodynamic evaluation using Doppler
      echocardiography. Most of these measurements are easily obtained and provide a
      safe alternative to invasive hemodynamic assessment. As Doppler echocardiography
      is able to provide additional valuable information, such as cardiac systolic and
      diastolic function, and the presence of pericardial and pleural effusions, which
      can play a significant role in the patients' hemodynamic status, using this
      noninvasive modality in the daily practice for hemodynamic assessment can prove
      an alternative to invasive measures in selected patients as well as a
      complementary tool for those still in need of invasive monitoring. 

PMID- 24135015
TI  - Sense of coherence and pain experience in older age.
AB  - BACKGROUND: We investigate to what extent pain in older individuals is predicted
      by on the one hand chronic morbidity as a resistance deficit, and on the other
      hand psychological resistance resources and the sense of coherence. For the first
      time, we tested the salutogenic hypothesis that the sense of coherence mediates
      the relationship between resources/deficits and pain. METHODS: In our
      questionnaire study, we assessed selected psychological resistance resources
      (self-esteem, generalized self-efficacy, optimism, and social support), the
      number of self-reported medical diagnoses of chronic illness, the sense of
      coherence, and pain (SF-36 Bodily Pain subscale) in a sample of 387 older persons
      (at the mean age of 73.8 years). RESULTS: Using hierarchical regression, we found
      that morbidity and sense of coherence were the only significant predictors of
      pain, with morbidity showing the strongest effect. Using path analysis, the sense
      of coherence was a mediator of the relationship between resistance
      resources/deficits and pain. CONCLUSIONS: With respect to our analytical model,
      in which pain experience was the criterion variable, morbidity and the sense of
      coherence are important predictors of pain. Moreover, we found evidence for the
      salutogenic idea that the sense of coherence represents a mediator variable as it
      pools resistance/deficits influences on pain. We recommend a prospective design
      to explore these assumed causal chains in future research.

PMID- 24135016
TI  - [Depression in smoking pregnant women: impact on motivation to quit smoking].
AB  - Despite the organization of smoking cessation program, the percentage of pregnant
      smokers remains too high in France. The knowledge of the factors limiting success
      of the attempt can help the smoking cessation. AIM: To evaluate the prevalence of
      depressive disorders in pregnant smokers compared to nonsmokers; assess their
      impact on motivation stopping smoking; verify their identification can be
      performed by midwives. MATERIALS AND METHODS: Prospective multicenter survey on
      792 women (435 smokers and 357 non-smokers), the assessment of the current
      depression is made by the Hospital Anxiety Depression scale, and motivation to
      quit smoking by the Richmond test. RESULTS: Pregnant smokers compared to non
      smokers, have more frequent depressive disorders (current: OR=2.4; history:
      OR=2). These problems do not decrease the motivation to quit, they are associated
      with a high nicotine dependence and low socioeconomic levels. Their testing can
      be done by midwives. CONCLUSION: Systematic screening for depression in pregnant
      women smoking could facilitate smoking cessation.

PMID- 24135017
TI  - [Quality of perinatal statistics from hospital discharge data: comparison with
      civil registration and the 2010 National Perinatal Survey].
AB  - OBJECTIVE: To compare hospital discharge data (PMSI) with data in the reference
      databases: vital statistics and National Perinatal Surveys (NPS) for the
      principal perinatal indicators. METHODS: Data concerning hospitalizations for
      delivery and childbirth were extracted from the PMSI 2010 database. The
      exhaustiveness was assessed by comparing discharge data with data from birth
      certificates. Indicators were compared with those in the 2010 NPS, which was
      based on a representative sample of births (n=15,000), using 95% confidence
      intervals. RESULTS: About 823,360 hospital abstracts with delivery and 829,351
      hospital abstracts with live births were considered. The exhaustiveness of the
      PMSI was 99.6% for live births in Metropolitan France. The distribution of
      maternal age, mode of delivery, birth weight and gestational age in the PMSI and
      NPS were very similar. In Metropolitan France, the prematurity rate was 6.9%
      (PMSI) vs. 6.6% [6.2-7.0] (NPS) and the rate of caesarean was 20.6% vs. 20.4%
      [19.8-21.1]. There were marked differences for the percentage of birth
      weights<2500g and for maternal diseases. CONCLUSION: The routine use of the PMSI
      for some indicators for follow-up purposes is foreseeable. Validation studies are
      still necessary for maternal diseases, for which recording is less standardized.

PMID- 24135018
TI  - Analysis of cognition, motor performance and anxiety in young and aged tumor
      necrosis factor alpha receptor 1 and 2 deficient mice.
AB  - TNF-alpha plays important functional roles in the central nervous system during
      normal physiological circumstances via intricate signaling mechanisms between its
      receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Although the roles
      of TNFR1 and TNFR2 in the diseased brain have received considerable attention,
      their functions on behavior and cognition in a non-inflammatory physiological
      aged environment are still unknown. In the present study we investigated the
      functional roles of TNFR1 and TNFR2 in learning and memory, motor performance and
      anxiety-like behavior via several behavioral and cognitive assessments in young
      and aged mice, deficient of either TNFR1 or TNFR2. Results from this study show
      that deletion of TNFR2 impairs novel object recognition, spatial memory
      recognition, contextual fear conditioning, motor performance and can increase
      anxiety-like behavior in young adult mice. Concerning the functions of TNFR1 and
      TNFR2 functioning in an aged environment, age caused memory impairment in spatial
      memory recognition independent of genotype. However, both young and aged mice
      deficient of TNFR2 performed poorly in the contextual fear conditioning test.
      These mice displayed decreased anxiety-like behavior, whereas mice deficient of
      TNFR1 were insusceptible to the effect of aging on anxiety-like behavior. This
      study provides novel knowledge on TNFR1 and TNFR2 functioning in behavior and
      cognition in young and aged mice in a non-inflammatory physiological environment.

PMID- 24135019
TI  - Regulation of ABCA1 protein expression and function in hepatic and pancreatic
      islet cells by miR-145.
AB  - OBJECTIVE: The ATP-binding cassette transporter A1 (ABCA1) protein maintains
      cellular cholesterol homeostasis in several different tissues. In the liver,
      ABCA1 is crucial for high-density lipoprotein biogenesis, and in the pancreas
      ABCA1 can regulate insulin secretion. In this study, our aim was to identify
      novel microRNAs that regulate ABCA1 expression in these tissues. APPROACH AND
      RESULTS: We combined multiple microRNA prediction programs to identify 8
      microRNAs that potentially regulate ABCA1. A luciferase reporter assay
      demonstrated that 5 of these microRNAs (miR-148, miR-27, miR-144, miR-145, and
      miR-33a/33b) significantly repressed ABCA1 3'-untranslated region activity with
      miR-145 resulting in one of the larger decreases. In hepatic HepG2 cells, miR-145
      can regulate both ABCA1 protein expression levels and cholesterol efflux
      function. In murine islets, an increase in miR-145 expression decreased ABCA1
      protein expression, increased total islet cholesterol levels, and decreased
      glucose-stimulated insulin secretion. Inhibiting miR-145 produced the opposite
      effect of increasing ABCA1 protein levels and improving glucose-stimulated
      insulin secretion. Finally, increased glucose levels in media significantly
      decreased miR-145 levels in cultured pancreatic beta cells. These findings
      suggest that miR-145 is involved in glucose homeostasis and is regulated by
      glucose concentration. CONCLUSIONS: Our studies demonstrate that miR-145
      regulates ABCA1 expression and function, and inhibiting this microRNA represents
      a novel strategy for increasing ABCA1 expression, promoting high-density
      lipoprotein biogenesis in the liver, and improving glucose-stimulated insulin
      secretion in islets.

PMID- 24135020
TI  - Tangeretin regulates platelet function through inhibition of phosphoinositide 3
      kinase and cyclic nucleotide signaling.
AB  - OBJECTIVE: Dietary flavonoids have long been appreciated in reducing
      cardiovascular disease risk factors, but their mechanisms of action are complex
      in nature. In this study, the effects of tangeretin, a dietary flavonoid, were
      explored on platelet function, signaling, and hemostasis. APPROACH AND RESULTS:
      Tangeretin inhibited agonist-induced human platelet activation in a concentration
      dependent manner. It inhibited agonist-induced integrin alphaIIbbeta3 inside-out
      and outside-in signaling, intracellular calcium mobilization, and granule
      secretion. Tangeretin also inhibited human platelet adhesion and subsequent
      thrombus formation on collagen-coated surfaces under arterial flow conditions in
      vitro and reduced hemostasis in mice. Further characterization to explore the
      mechanism by which tangeretin inhibits platelet function revealed distinctive
      effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3
      kinase-mediated signaling and increase cGMP levels in platelets, although
      phosphodiesterase activity was unaffected. Consistent with increased cGMP levels,
      tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein
      at S239. CONCLUSIONS: This study provides support for the ability and mechanisms
      of action of dietary flavonoids to modulate platelet signaling and function,
      which may affect the risk of thrombotic disease.

PMID- 24135021
TI  - Role of IkappaB kinase-beta in the growth-promoting effects of angiotensin II in
      vitro and in vivo.
AB  - OBJECTIVE: Angiotensin II (Ang II) is implicated in processes underlying the
      development of arterial wall remodeling events, including cellular hypertrophy
      and inflammation. We previously documented the activation of IkappaB kinase-beta
      (IKKbeta) in Ang II-treated cells, a kinase involved in inflammatory reactions.
      In light of a study suggesting a role of IKKbeta in angiogenesis through its
      effect on the tuberous sclerosis (TSC)1/2-mammalian target of rapamycin complex 1
      pathway in cancer cells, we hypothesized that targeting IKKbeta could reduce
      arterial remodeling events by affecting both the inflammatory and the growth
      promoting response of Ang II. APPROACH AND RESULTS: Treatment of aortic vascular
      smooth muscle cells with Ang II induced the rapid and sustained phosphorylation
      of TSC1 on Ser511, which paralleled the activation of effectors of the mammalian
      target of rapamycin complex 1 pathway. Furthermore, we show that Ser511 of TSC1
      acted as a phosphoacceptor site for Ang II-activated IKKbeta. Consistent with
      this, the use of different short hairpin RNA constructs targeting IKKbeta reduced
      Ang II-induced TSC1, S6 kinase, and eukaryotic translation initiation factor 4E
      binding protein 1 phosphorylation and the rate of protein synthesis.
      Overexpression of TSC1 lacking Ser511 in vascular smooth muscle cells also
      exerted detrimental effects on the hypertrophic effect of Ang II. Furthermore,
      the selective IKKbeta inhibitor N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2
      methylnicotinamide reduced the inflammatory response and dose-dependently
      diminished Ang II-induced TSC1 phosphorylation and effectors of the mammalian
      target of rapamycin complex 1 pathway, leading to inhibition of protein synthesis
      in vitro and in rat arteries in vivo. CONCLUSIONS: Our findings provide new
      insights into the molecular understanding of the pathological role of Ang II and
      assist in identifying the beneficial effects of IKKbeta inhibition for the
      treatment of cardiovascular diseases.

PMID- 24135022
TI  - Hedgehog-dependent regulation of angiogenesis and myogenesis is impaired in aged
      mice.
AB  - OBJECTIVE: The purpose of this study is to further document alteration of signal
      transduction pathways, more particularly of hedgehog (Hh) signaling, causing
      impaired ischemic muscle repair in old mice. APPROACH AND RESULTS: We used 12
      week-old (young mice) and 20- to 24-month-old C57BL/6 mice (old mice) to
      investigate the activity of Hh signaling in the setting of hindlimb ischemia
      induced angiogenesis and skeletal muscle repair. In this model, delayed ischemic
      muscle repair observed in old mice was associated with an impaired upregulation
      of Gli1. Sonic Hh expression was not different in old mice compared with young
      mice, whereas desert Hh (Dhh) expression was downregulated in the skeletal muscle
      of old mice both in healthy and ischemic conditions. The rescue of Dhh expression
      by gene therapy in old mice promoted ischemia-induced angiogenesis and increased
      nerve density; nevertheless, it failed to promote myogenesis or to increase Gli1
      mRNA expression. After further investigation, we found that, in addition to Dhh,
      smoothened expression was significantly downregulated in old mice. We used
      smoothened haploinsufficient mice to demonstrate that smoothened knockdown by 50%
      is sufficient to impair activation of Hh signaling and ischemia-induced muscle
      repair. CONCLUSIONS: The present study demonstrates that Hh signaling is impaired
      in aged mice because of Dhh and smoothened downregulation. Moreover, it shows
      that hegdehog-dependent regulation of angiogenesis and myogenesis involves
      distinct mechanisms.

PMID- 24135023
TI  - Pericyte regulation of vascular remodeling through the CXC receptor 3.
AB  - OBJECTIVE: To understand the role, if any, played by pericytes in the regulation
      of newly formed vessels during angiogenesis. In this study, we investigate
      whether pericytes regulate the number of nascent endothelial tubes. APPROACH AND
      RESULTS: Using an in vitro angiogenesis assay (Matrigel assay), we demonstrate
      that pericytes can inhibit vessel formation and induce vessel dissociation via
      CXCR3-induced involution of the endothelial cells. In a coculture Matrigel assay
      for cord formation, pericytes prevented endothelial cord formation of human
      dermal microvascular endothelial cells but not umbilical vein endothelial cells.
      Blockade of endothelial CXCR3 function or expression inhibited the repressing
      effect of the pericytes. We further show that pericytes are also able to induce
      regression of newly formed microvascular cords through CXCR3 activation of
      calpain. When CXCR3 function was inhibited by a neutralizing antibody or
      downregulated by siRNA, cord regression mediated by pericytes was abolished.
      CONCLUSIONS: We show for the first time that pericytes regulate angiogenic vessel
      formation, and that this is mediated through CXCR3 expressed on endothelial
      cells. This suggests a role for pericytes in the pruning of immature vessels
      overproduced during wound repair.

PMID- 24135025
TI  - Effects of permafrost thaw on carbon emissions under aerobic and anaerobic
      environments in the Great Hing'an Mountains, China.
AB  - The carbon (C) pool of permafrost peatland is very important for the global C
      cycle. Little is known about how permafrost thaw could influence C emissions in
      the Great Hing'an Mountains of China. Through aerobic and anaerobic incubation
      experiments, we studied the effects of permafrost thaw on CH4 and CO2 emissions.
      The rates of CH4 and CO2 emissions were measured at -10, 0 and 10 degrees C.
      Although there were still C emissions below 0 degrees C, rates of CH4 and CO2
      emissions significantly increased with permafrost thaw under aerobic and
      anaerobic conditions. The C release under aerobic conditions was greater than
      under anaerobic conditions, suggesting that permafrost thaw and resulting soil
      environment change should be important influences on C emissions. However, CH4
      stored in permafrost soils could affect accurate estimation of CH4 emissions from
      microbial degradation. Calculated Q10 values in the permafrost soils were
      significantly higher than values in active-layer soils under aerobic conditions.
      Our results highlight that permafrost soils have greater potential
      decomposability than soils of the active layer, and such carbon decomposition
      would be more responsive to the aerobic environment.

PMID- 24135024
TI  - Crucial role of ROCK2 in vascular smooth muscle cells for hypoxia-induced
      pulmonary hypertension in mice.
AB  - OBJECTIVE: Rho/Rho-kinase (ROCK) pathway in vascular smooth muscle cells (VSMCs)
      plays an important role in the pathogenesis of cardiovascular diseases, including
      pulmonary arterial hypertension (PAH). Rho-kinase has 2 isoforms, ROCK1 and
      ROCK2, with different functions in different cells; ROCK1 for circulating
      inflammatory cells and ROCK2 for the vasculature. In the present study, we aimed
      to examine whether ROCK2 in VSMC is involved in the pathogenesis of PAH. APPROACH
      AND RESULTS: In patients with PAH, the expression of ROCK2 was increased in
      pulmonary arterial media and primary pulmonary arterial smooth muscle cells when
      compared with controls. To investigate the role of ROCK2 in VSMC, we generated
      VSMC-specific heterozygous ROCK2-deficient (ROCK2(+/-)) mice and VSMC-specific
      ROCK2-overexpressing transgenic (ROCK2-Tg) mice. The extent of hypoxia-induced
      pulmonary hypertension was reduced in ROCK2(+/-) mice and was enhanced in ROCK2
      Tg mice compared with respective littermates. The protein expression of ROCK
      activity and phosphorylated extracellular signal-regulated kinase and the number
      of Ki67-positive proliferating cells in the lung were reduced in ROCK2(+/-) mice
      and were increased in ROCK2-Tg mice compared with respective littermates. In
      cultured mouse aortic VSMC, migration and proliferation activities were reduced
      in ROCK2(+/-) mice, and migration activity was increased in ROCK2-Tg mice
      compared with respective littermates. In addition, in primary pulmonary arterial
      smooth muscle cells from a patient with PAH, ROCK2 was required for migration and
      proliferation through ROCK and extracellular signal-regulated kinase activation.
      CONCLUSIONS: ROCK2 in VSMC contributes to the pathogenesis of PAH.

PMID- 24135026
TI  - Quantifying charge transfer energies at donor-acceptor interfaces in small
      molecule solar cells with constrained DFTB and spectroscopic methods.
AB  - Charge transfer states around the donor-acceptor interface in an organic solar
      cell determine the device performance in terms of the open circuit voltage. In
      the present work, we propose a computational scheme based on constrained density
      functional tight binding theory (c-DFTB) to assess the energy of the lowest
      charge transfer (CT) state in such systems. A comparison of the c-DFTB scheme
      with Hartree-Fock based configuration interaction of singles (CIS) and with time
      dependent density functional theory (TD-DFT) using the hybrid functional B3LYP
      reveals that CIS and c-DFTB reproduce the correct Coulomb asymptotics between
      cationic donor and anionic acceptor configurations, whereas TD-DFT gives a
      qualitatively wrong excitation energy. Together with an embedding scheme
      accounting for the polarizable medium, this c-DFTB scheme is applied to several
      donor-acceptor combinations used in molecular solar cells. The external quantum
      efficiency of photovoltaic cells based on zinc phthalocyanine-C60 blends reveals
      a CT band remaining much narrower than the density of states of acceptor HOMO and
      donor LUMO, an observation which can be interpreted in a natural way in terms of
      Marcus transfer theory. A detailed comparison with c-DFTB calculations reveals an
      energy difference of 0.32 eV between calculated and observed absorption from the
      electronic ground state into the CT state. In a blend of a functionalized
      thiophene and C60, the photoluminescence spectra differ significantly from neat
      films, allowing again an assignment to CT states. The proposed computational
      scheme reproduces the observed trends of the observed open circuit voltages in
      photovoltaic devices relying on several donor-acceptor blends, finding an offset
      of 1.16 eV on average. This value is similar as in polymer-fullerene photovoltaic
      systems where it amounts to about 0.9 eV, indicating that the photophysics of CT
      states in molecular donor-acceptor blends and in polymer-fullerene blends are
      governed by the same mechanisms. 

PMID- 24135027
TI  - Telephone-based health coaching for chronically ill patients: study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: The rising prevalence of chronic conditions constitutes a major
      burden for patients and healthcare systems and is predicted to increase in the
      upcoming decades. Improving the self-management skills of patients is a strategy
      to steer against this burden. This could lead to better outcomes and lower
      healthcare costs. Health coaching is one method for enhancing the self-management
      of patients and can be delivered by phone. The effects of telephone-based health
      coaching are promising, but still inconclusive. Economic evaluations and studies
      examining the transferability of effects to different healthcare systems are
      still rare. Aim of this study is to evaluate telephone-based health coaching for
      chronically ill patients in Germany. METHODS/DESIGN: The study is a prospective
      randomized controlled trial comparing the effects of telephone-based health
      coaching with usual care during a 4-year time period. Data are collected at
      baseline and after 12, 24 and 36 months. Patients are selected based on one of
      the following chronic conditions: diabetes, coronary artery disease, asthma,
      hypertension, heart failure, COPD, chronic depression or schizophrenia. The
      health coaching intervention is carried out by trained nurses employed by a
      German statutory health insurance. The frequency and the topics of the health
      coaching are manual-based but tailored to the patients' needs and medical
      condition, following the concepts of motivational interviewing, shared decision
      making and evidence-based-medicine. Approximately 12,000 insurants will be
      enrolled and randomized into intervention and control groups. Primary outcome is
      the time until hospital readmission within two years after enrolling in the
      health coaching, assessed by routine data. Secondary outcomes are patient
      reported outcomes like changes in quality of life, depression and anxiety and
      clinical values assessed with questionnaires. Additional secondary outcomes are
      further economic evaluations like health service use as well as costs and
      hospital readmission rates. The statistical analyses includes intention-to-treat
      and as-treated principles. The recruitment will be completed in September 2014.
      DISCUSSION: This study will provide evidence regarding economic and clinical
      effects of telephone-delivered health coaching. Additionally, this study will
      show whether health coaching is an adequate option for the German healthcare
      system to address the growing burden of chronic diseases. TRIAL REGISTRATION:
      German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS)
      DRKS00000584.

PMID- 24135028
TI  - [Evaluation of temporality semantic knowledge in normal aging and in mild and
      moderate stages of Alzheimer's disease].
AB  - OBJECTIVE: Episodic and semantic processes are involved in temporality used in
      daily life. Episodic memory permits one to place an event on the time axis, while
      semantic memory makes us aware of the time segmentation and its symbolic
      representation. Memory of the knowledge connected to the passing of time is
      materialized on the calendar and can be seen symbolically on the dial of a clock.
      In AD, semantic memory processes are preserved longer than processes related to
      episodic memory. We wonder whether the specific field of knowledge about time is
      altered during AD. METHODOLOGY: We validated a specific evaluation with a control
      group (354 healthy subjects). Then we applied this battery to assess AD patients
      to appreciate the feasibility of this tool for this population. We then compared
      22 AD patients with a control group matched for age, sex and educational level.
      Our clinical scale of temporal semantic knowledge consists of four parts: (a)
      hour reading with a.m. and p.m. hours; (b) using a clock: 12 clock faces with the
      hour numbers already placed: the patient draws hour and minute hands for various
      hours; (c) temporal segmentation: exploration of the knowledge on daytime scale
      and of the calendar; (d) time duration estimation: calculate how long the
      interview has lasted after indicating the time of its beginning and its end, then
      the time between 10.40 to 12.00. RESULTS: While age and educational level had an
      influence on all the scores, in the two groups control and patients, gender did
      not. Temporal segmentation, independent of the cultural level, revealed the best
      acquired knowledge in our control population. All the scores differentiated
      patients from control subjects. The temporal semantic knowledge correlated with
      the AD severity seemed to be correlated with the attention, verbal comprehension,
      and some components of executive functions, but was not related to the clock
      drawing test result. Depression did not have any influence on this scale in our
      AD group. DISCUSSION: The temporal semantic knowledge clinical scale shows
      differential alterations, notably in hour reading and using a clock, and less in
      temporal segmentation. CONCLUSION: Temporal semantic knowledge is altered in AD.
      The diagnosis and follow-up of these alterations allow professionals and
      caregivers to consider adaptations of the patient's environment according to
      their needs.

PMID- 24135029
TI  - Effects of different trehalose concentrations in a warming medium on embryo
      survival and clinical outcomes in vitrified human embryos.
AB  - BACKGROUND/AIMS: In the present study, we examined the effects of different
      concentrations of trehalose in a warming medium on both embryo survival and
      clinical outcomes in vitrified-warmed embryo transfer cycles. METHODS: We
      retrospectively analyzed a total of 209 vitrified-warmed cycles from 177 patients
      who underwent in vitro fertilization or intracytoplasmic sperm injection and
      embryo transfer. Embryos were cryopreserved by the vitrification method and
      warmed in solutions containing either 0.5 or 1.0 M trehalose. We compared the 0.5
      and 1.0 M trehalose warming solution groups with respect to the embryo survival
      rate after warming and clinical outcomes. RESULTS: The embryo survival rate in
      the 1.0 M trehalose group (96.5%) was significantly higher than that in the 0.5 M
      trehalose group (57.0%). The percentage of embryo transfers after warming in the
      1.0 M trehalose group (94.3%) was significantly higher than that in the 0.5 M
      trehalose group (83.7%). The clinical pregnancy rate in the 1.0 M trehalose group
      (25.0%) was significantly higher than that in the 0.5 M trehalose group (11.1%).
      CONCLUSION: Embryo survival and clinical pregnancy rates were higher when a 1.0 M
      trehalose solution was used than when a 0.5 M trehalose solution was used during
      the embryo warming process.

PMID- 24135030
TI  - Clinical identification of patients readmitted to hospitals: why patients return.
AB  - BACKGROUND: Increased interest in hospital outcomes has supported the need for
      clear and useful identification of patients who are readmitted. These patients
      have frequently been identified by the principal diagnosis of the initial
      admission. FINDINGS: In order to evaluate the effectiveness of identifying
      patients who were subsequently readmitted, those with two frequently encountered
      conditions, principal diagnoses of congestive heart failure and pneumonia, in the
      hospitals of Syracuse New York were evaluated. Both populations had large
      proportions of readmissions involved with principal diagnoses other than
      pneumonia. For patients with heart failure, a majority of readmitted patients had
      other diagnoses for two of the hospitals. For patients with pneumonia, a majority
      of patients had other diagnoses for all of the hospitals. CONCLUSIONS: The data
      suggested that many patients who were subsequently readmitted are best identified
      as medicine patients with multiple diagnoses, rather than a single one. This
      approach addresses the need to manage a wide range of conditions for hospital
      readmissions, rather than a narrow approach on individual diagnosis.

PMID- 24135031
TI  - Spinal infiltration: have you modified your practice?

PMID- 24135032
TI  - Perfusion imaging in renal diseases.
AB  - Functional imaging of the kidney using radiological techniques has a great
      potential of development because the functional parameters, which can be
      approached non-invasively, are multiple. CT can provide measurement of perfusion
      and glomerular filtration but has the inconvenient to deliver irradiation and
      potentially nephrotoxicity due to iodine agents in this context. Sonography is
      able to evaluate perfusion only but quantification remains problematic.
      Therefore, MR imaging shows the greatest flexibility measuring blood volume and
      perfusion as well as split renal function. The main applications of perfusion
      imaging of the kidney are vascular diseases, as renal artery stenosis, renal
      obstruction and follow-up of renal tumors under antiangiogenic therapy. However,
      full clinical validation of these methods and the evaluation of their clinical
      impact are still often worthwhile. 

PMID- 24135033
TI  - Implicit and explicit self-esteem and their reciprocal relationship with symptoms
      of depression and social anxiety: a longitudinal study in adolescents.
AB  - BACKGROUND AND OBJECTIVES: A negative self-view is a prominent factor in most
      cognitive vulnerability models of depression and anxiety. Recently, there has
      been increased attention to differentiate between the implicit (automatic) and
      the explicit (reflective) processing of self-related evaluations. This
      longitudinal study aimed to test the association between implicit and explicit
      self-esteem and symptoms of adolescent depression and social anxiety disorder.
      Two complementary models were tested: the vulnerability model and the scarring
      effect model. METHOD: Participants were 1641 first and second year pupils of
      secondary schools in the Netherlands. The Rosenberg Self-Esteem Scale, self
      esteem Implicit Association Test and Revised Child Anxiety and Depression Scale
      were completed to measure explicit self-esteem, implicit self-esteem and symptoms
      of social anxiety disorder (SAD) and major depressive disorder (MDD),
      respectively, at baseline and two-year follow-up. RESULTS: Explicit self-esteem
      at baseline was associated with symptoms of MDD and SAD at follow-up.
      Symptomatology at baseline was not associated with explicit self-esteem at follow
      up. Implicit self-esteem was not associated with symptoms of MDD or SAD in either
      direction. LIMITATIONS: We relied on self-report measures of MDD and SAD
      symptomatology. Also, findings are based on a non-clinical sample. CONCLUSIONS:
      Our findings support the vulnerability model, and not the scarring effect model.
      The implications of these findings suggest support of an explicit self-esteem
      intervention to prevent increases in MDD and SAD symptomatology in non-clinical
      adolescents.

PMID- 24135034
TI  - A behavioral test of contamination fear in excessive health anxiety.
AB  - BACKGROUND AND OBJECTIVES: Health anxiety is characterized by a preoccupation
      with the possibility of having a serious health condition or disease.
      Contemporary conceptualizations of health anxiety have improved in recent years
      to incorporate a fear of acquiring an illness; however, there is limited
      experimental data demonstrating the presence of fear of contamination among
      health anxious individuals. METHOD: The present study utilized behavior approach
      tasks (BATs) to examine the degree to which contamination fear is present in
      elevated health anxiety. Participants were 60 undergraduate students who reported
      elevated health anxiety, contamination fear, or no anxiety about either health or
      contamination. Participants completed four BATS from which avoidance, anxiety,
      and disgust ratings were derived. RESULTS: Health anxious and contamination
      fearful individuals exhibited a similar degree of avoidance during the BATs.
      Contamination fearful participants reported significantly more anxiety and
      disgust relative to the non-anxious controls, but not the health anxious
      participants. Health anxious participants did not report more anxiety or disgust
      than the non-anxious participants. LIMITATIONS: The use of an analogue sample may
      limit the extension of these findings to clinical populations. Additionally, the
      role of general negative affect could not be reliably determined in the absence
      of an anxious control group. CONCLUSIONS: These findings suggest that
      contamination fear may be a source of conceptual overlap between health anxiety
      and other disorders characterized by contamination fear. This highlights the
      importance of considering contamination fear in excessive health anxiety.

PMID- 24135036
TI  - Mutations in MAP3K1 tilt the balance from SOX9/FGF9 to WNT/beta-catenin
      signaling.
AB  - In-frame missense and splicing mutations (resulting in a 2 amino acid insertion
      or a 34 amino acid deletion) dispersed through the MAP3K1 gene tilt the balance
      from the male to female sex-determining pathway, resulting in 46,XY disorder of
      sex development. These MAP3K1 mutations mediate this balance by enhancing
      WNT/beta-catenin/FOXL2 expression and beta-catenin activity and by reducing
      SOX9/FGF9/FGFR2/SRY expression. These effects are mediated at multiple levels
      involving MAP3K1 interaction with protein co-factors and phosphorylation of
      downstream targets. In transformed B-lymphoblastoid cell lines and NT2/D1 cells
      transfected with wild-type or mutant MAP3K1 cDNAs under control of the
      constitutive CMV promoter, these mutations increased binding of RHOA, MAP3K4,
      FRAT1 and AXIN1 and increased phosphorylation of p38 and ERK1/2. Overexpressing
      RHOA or reducing expression of MAP3K4 in NT2/D1 cells produced phenocopies of the
      MAP3K1 mutations. Using siRNA knockdown of RHOA or overexpressing MAP3K4 in
      NT2/D1 cells produced anti-phenocopies. Interestingly, the effects of the MAP3K1
      mutations were rescued by co-transfection with wild-type MAP3K4. Although MAP3K1
      is not usually required for testis determination, mutations in this gene can
      disrupt normal development through the gains of function demonstrated in this
      study. 

PMID- 24135035
TI  - A methylome-wide study of aging using massively parallel sequencing of the methyl
      CpG-enriched genomic fraction from blood in over 700 subjects.
AB  - The central importance of epigenetics to the aging process is increasingly being
      recognized. Here we perform a methylome-wide association study (MWAS) of aging in
      whole blood DNA from 718 individuals, aged 25-92 years (mean = 55). We sequenced
      the methyl-CpG-enriched genomic DNA fraction, averaging 67.3 million reads per
      subject, to obtain methylation measurements for the ~27 million autosomal CpGs in
      the human genome. Following extensive quality control, we adaptively combined
      methylation measures for neighboring, highly-correlated CpGs into 4 344 016 CpG
      blocks with which we performed association testing. Eleven age-associated
      differentially methylated regions (DMRs) passed Bonferroni correction (P-value <
      1.15 * 10(-8)). Top findings replicated in an independent sample set of 558
      subjects using pyrosequencing of bisulfite-converted DNA (min P-value < 10(-30)).
      To examine biological themes, we selected 70 DMRs with false discovery rate of
      <0.1. Of these, 42 showed hypomethylation and 28 showed hypermethylation with
      age. Hypermethylated DMRs were more likely to overlap with CpG islands and
      shores. Hypomethylated DMRs were more likely to be in regions associated with
      polycomb/regulatory proteins (e.g. EZH2) or histone modifications H3K27ac,
      H3K4m1, H3K4m2, H3K4m3 and H3K9ac. Among genes implicated by the top DMRs were
      protocadherins, homeobox genes, MAPKs and ryanodine receptors. Several of our
      DMRs are at genes with potential relevance for age-related disease. This study
      successfully demonstrates the application of next-generation sequencing to MWAS,
      by interrogating a large proportion of the methylome and returning potentially
      novel age DMRs, in addition to replicating several loci implicated in previous
      studies using microarrays. 

PMID- 24135037
TI  - Efficacy and safety of erythropoietin and intravenous iron in perioperative blood
      management: a systematic review.
AB  - The use of erythropoietin (EPO) and intravenous (IV) iron as bloodless
      therapeutic modalities is being explored in the current era of restrictive
      transfusion strategies and perioperative blood management. It is unclear,
      however, whether the evidence in the literature supports their safety and
      efficacy in reducing perioperative red cell transfusions. Adhering to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we
      conducted a systematic review to evaluate their use in a variety of perioperative
      settings. We performed a literature search of English articles published between
      July 1997 and July 2012 in MEDLINE via PubMed, The Cochrane Library, and CINAHL.
      Only studies with a comparator group were eligible for inclusion. Twenty-four
      randomized controlled trials (RCTs) and 15 nonrandomized studies were included in
      the final review. Using the Cochrane risk of bias tool, 8 RCTs were assessed to
      be at low risk for methodological bias. Of these, however, only 4 RCTs were
      adequately powered to detect a reduction in transfusion rates. Patients with
      preoperative iron deficiency anemia may have an earlier and more robust
      hemoglobin recovery with preoperative IV iron therapy than with oral iron
      supplementation. A short preoperative regimen of EPO, or a single dose of EPO
      plus IV iron in the preoperative or intraoperative period, may significantly
      reduce transfusion rates (number needed to treat to avoid any transfusion ranged
      from 3 to 6). With regard to the safety of erythropoietin-stimulating agent
      therapy, IV iron appears to be as well tolerated as oral iron; however, the
      incidence of severe anaphylactic-type reactions attributable to IV iron is
      difficult to estimate in prospective trials because of its relatively infrequent
      occurrence. Furthermore, EPO may increase the risk of thromboembolism in spinal
      surgery patients who receive mechanical antithrombotic prophylaxis in the
      perioperative period so pharmacological thromboprophylaxis is advised. Future low
      risk of bias, adequately powered prospective efficacy, and safety trials in
      various surgical settings that traditionally require red cell transfusions would
      be required to make evidenced-based conclusions about the clinical significance
      of erythropoietin-stimulating agent as a transfusion avoidance strategy in
      perioperative blood management. 

PMID- 24135038
TI  - The unsolved problem of organ allocation in times of organ shortage: the German
      solution?
AB  - The concept of the International and Inter-Society Co-ordination Committee (I2C2)
      has been introduced at the International Society for Heart and Lung
      Transplantation (ISHLT) annual meeting in Prague. It is a pivotal role of I2C2 to
      develop formal relationships with other societies involved in the field of
      thoracic transplantation to attain mutual benefits, share membership, and achieve
      common goals. This editorial is on behalf of an initiative of the I2C2 committee
      chairs to report about a specific problem related to thoracic transplantation in
      1 European country and the approach chosen by the local national authorities,
      together with the transplant community, to address this issue. 

PMID- 24135039
TI  - Leveling the playing field in adult heart transplantation.

PMID- 24135040
TI  - Choosing the right lungs for the right patient.

PMID- 24135041
TI  - High-intensity interval training in patients with cardiovascular diseases and
      heart transplantation.

PMID- 24135042
TI  - Nucleic acid detection using G-quadruplex amplification methodologies.
AB  - In the last decade, there has been an explosion in the use of G-quadruplex labels
      to detect various analytes, including DNA/RNA, proteins, metals and other
      metabolites. In this review, we focus on strategies for the detection of nucleic
      acids, using G-quadruplexes as detection labels or as enzyme labels that amplify
      detection signals. Methods to detect other analytes are briefly mentioned. We
      highlight various strategies, including split G-quadruplex, hemin-G-quadruplex
      conjugates, molecular beacon G-quadruplex or inhibited G-quadruplex probes. The
      tandem use of G-quadruplex labels with various DNA-modifying enzymes, such as
      polymerases (used for rolling circle amplification), exonucleases and
      endonucleases, is also discussed. Some of the detection modalities that are
      discussed in this review include fluorescence, colorimetric, chemiluminescence,
      and electrochemical methods. 

PMID- 24135043
TI  - The cost of postabortion care and legal abortion in Colombia.
AB  - CONTEXT: Although Colombia partially liberalized its abortion law in 2006, many
      abortions continue to occur outside the law and result in complications.
      Assessing the costs to the health care system of safe, legal abortions and of
      treating complications of unsafe, illegal abortions has important policy
      implications. METHODS: The Post-Abortion Care Costing Methodology was used to
      produce estimates of direct and indirect costs of postabortion care and direct
      costs of legal abortions in Colombia. Data on estimated costs were obtained
      through structured interviews with key informants at a randomly selected sample
      of facilities that provide abortion-related care, including 25 public and private
      secondary and tertiary facilities and five primary-level private facilities that
      provide specialized reproductive health services. RESULTS: The median direct cost
      of treating a woman with abortion complications ranged from $44 to $141 (in U.S.
      dollars), representing an annual direct cost to the health system of about $14
      million per year. A legal abortion at a secondary or tertiary facility was costly
      (medians, $213 and $189, respectively), in part because of the use of dilation
      and curettage, as well as because of administrative barriers. At specialized
      facilities, where manual vacuum aspiration and medication abortion are used, the
      median cost of provision was much lower ($45). CONCLUSIONS: Provision of
      postabortion care and legal abortion services at higher-level facilities results
      in unnecessarily high health care costs. These costs can be reduced significantly
      by providing services in a timely fashion at primary-level facilities and by
      using safe, noninvasive and less costly abortion methods.

PMID- 24135044
TI  - Contraception and abortion in a low-fertility setting: the role of seasonal
      migration.
AB  - CONTEXT: Seasonal labor migration is common among men in many former Soviet
      republics. Little research has examined contraceptive use and induced abortion
      among women in such low-fertility, high-migration settings, according to
      husband's migration status. METHODS: Combined data from 2,280 respondents of two
      surveys of married women aged 18-45 in rural Armenia-one conducted in 2005 and
      one in 2007-were used. Logistic regression analyses examined whether a husband's
      migration status was associated with his wife's current use of the pill or the
      IUD, or with the probability that she had had a pregnancy that ended in induced
      abortion. Additional analyses were conducted to determine whether relationships
      were moderated by household wealth. RESULTS: Women with a migrant husband were
      less likely than those with a nonmigrant husband to be currently using the pill
      or the IUD (odds ratio, 0.6); with increased household wealth, the likelihood of
      method use increased among women with a nonmigrant husband, but decreased
      slightly among women with a migrant husband. Overall, the probability that a
      pregnancy ended in abortion did not differ by migration status; however, the
      likelihood of abortion increased with wealth among women married to a nonmigrant,
      but not among those married to a migrant. CONCLUSIONS: Despite their husband's
      absence, women married to a migrant may have an unwanted pregnancy rate similar
      to that of women married to a nonmigrant. Improved access to modern contraceptive
      methods is likely to be positively associated with contraceptive use among women
      with a nonmigrant husband, but not among those with a migrant husband.

PMID- 24135045
TI  - Reducing unmet need by supporting women with met need.
AB  - CONTEXT: The 2012 London Summit on family planning set a goal of providing modern
      contraceptives to 120 million women with unmet need by 2020. Reducing the high
      rate of contraceptive discontinuation by facilitating switching among methods
      will play a critical role in meeting that goal. METHODS: Data collected from
      married women in Demographic and Health Surveys conducted in 34 countries between
      2005 and 2010 were used to estimate the potential contribution of contraceptive
      discontinuation to current and future unmet need. An indicator of relevant
      discontinuation was created by calculating the proportion of past users with an
      unmet need for modern methods among ever-users. Regression analyses identified
      associations between this indicator and access to and composition of methods.
      RESULTS: Women who had discontinued method use and subsequently had unmet need at
      the survey accounted for 38% of the total estimated unmet need. These past users
      represented 19% of women who had ever used modern methods. Both the access to and
      composition of available methods were associated with a reduction in the relevant
      discontinuation rate. The level of discontinuation in Sub-Saharan Africa was
      significantly higher than in other regions, in part due to differences in method
      availability. CONCLUSIONS: High contraceptive discontinuation in the past has
      contributed tens of millions of cases of unmet need, and discontinuation among
      current users will contribute even more cases in the future. Enabling past users
      with unmet need to resume use and encouraging current users to continue use of
      the same or another method could be an effective strategy to reduce future unmet
      need.

PMID- 24135046
TI  - Effectiveness of a behavior change communication intervention to improve
      knowledge and perceptions about abortion in Bihar and Jharkhand, India.
AB  - CONTEXT: Although abortion became legal in India in 1971, many women are unaware
      of the law. Behavior change communication interventions may be an effective way
      to promote awareness of the law and change knowledge of and perceptions about
      abortion, particularly in settings in which abortion is stigmatized. METHODS: To
      evaluate the effectiveness of a behavior change communication intervention to
      improve women's knowledge about India's abortion law and their perceptions about
      abortion, a quasi-experimental study was conducted in intervention and comparison
      districts in Bihar and Jharkhand. Household surveys were administered at baseline
      in 2008 and at follow-up in 2010 to independent, randomly selected cross
      sectional samples of rural married women aged 15-49. Logistic regression
      difference-in-differences models were used to assess program effectiveness.
      RESULTS: Analysis demonstrated program effectiveness in improving awareness and
      perceptions about abortion. The changes in the odds of knowing that abortion is
      legal and where to obtain safe abortion services were larger between baseline and
      follow-up in the intervention districts than the changes in odds observed in the
      comparison districts (odds ratios, 16.1 and 1.9, respectively). Similarly, the
      increase in women's perception of greater social support for abortion within
      their families and the increase in perceived self-efficacy with respect to family
      planning and abortion between baseline and follow-up was greater in the
      intervention districts than in the comparison districts (coefficients, 0.17 and
      0.18, respectively). CONCLUSIONS: Behavior change communication interventions can
      be effective in improving knowledge of and perceptions about abortion in settings
      in which lack of accurate knowledge hinders women's access to safe abortion
      services. Multiple approaches should be used when attempting to improve knowledge
      and perceptions about stigmatized health issues such as abortion.

PMID- 24135047
TI  - Risk and protective correlates of young women's first sexual experiences in
      Rakai, Uganda.
AB  - CONTEXT: Sexually active young women bear the brunt of the HIV epidemic in Sub
      Saharan Africa. Information is needed on risk and protective correlates at the
      family, partner and individual level for the design of programs to encourage
      safer sexual behaviors and reduce HIV risk among young women. METHODS: The study
      was conducted among 1,675 sexually experienced women aged 15-24 living in Rakai,
      Uganda. The sample was taken from an ongoing community cohort study initiated in
      1994 in 56 villages by the Rakai Health Sciences Program. Contextual variabless
      at the family, partner and individual levels were analyzed in relation to three
      outcome variables: sex before the age of 15, coerced first sex and condom use at
      first sex. RESULTS: At the family level, young females who did not live with both
      parents were more likely than those who did to have had sex before the age of 15
      and to have experienced sexual coercion at first sex. Those whose mothers had
      some secondary education and whose female caregiver did not consume alcohol had
      elevated odds of using a condom at first sex. Having initiated sex at age 15 or
      older was the strongest individual-level characteristic associated with having
      used a condom at first sex. CONCLUSIONS: Reproductive health interventions should
      target adolescents and their parents to delay the onset of sexual activity,
      prevent sexual coercion and encourage condom use. Both adolescents and their
      parents should be educated about the risks associated with different types of
      sexual partnerships.

PMID- 24135048
TI  - Epigenetic upregulation of CCL2 and CCL3 via histone modifications in
      infiltrating macrophages after peripheral nerve injury.
AB  - To gain insight into the epigenetic regulation of CC-chemokine ligand (CCL) 2 and
      CCL3, key players in the peripheral sensitization leading to neuropathic pain, we
      examined the relationship between histone H3 modification and the upregulation of
      these molecules using a mouse model of neuropathic pain after partial sciatic
      nerve ligation (PSL). We found that circuiting bone marrow (BM)-derived
      macrophages infiltrated into the injured sciatic nerve (SCN) using enhanced green
      fluorescent protein chimeric mice. The mRNA levels of CCL2, CCL3 and their
      receptors (CCR2 and CCR1/CCR5, respectively) were increased in the injured SCN.
      Chromatin immunoprecipitation assay revealed that levels of lysine 9-acetylated
      histone H3 (H3K9Ac) and lysine 4-trimethylated H3 (H3K4me(3)) in the promoter
      regions of the CCL2 and CCL3 genes were increased in the injured SCN after PSL,
      indicating the enhancement of gene expression. Immunoreactivity for H3K9Ac and
      H3K4me(3) was localized in the nuclei of infiltrating BM-derived cells and CCL
      expressing cells in the injured SCN. We observed H3K9Ac and H3K4me(3) mainly in
      the nuclei of recruited macrophages on day 7 after PSL. Furthermore, upregulation
      of CCLs and CCRs were suppressed by histone acetyltransferase inhibitor,
      anacardic acid. Taken together, our findings demonstrate that CCL2 and CCL3 are
      upregulated in the injured peripheral nerve through epigenetic histone
      modification in infiltrating immune cells such as macrophages. These chemokine
      cascades may subsequently elicit chronic neuroinflammation following nerve
      injury. 

PMID- 24135049
TI  - Self-management of chronic conditions in a rural and remote context.
AB  - Living in a rural or remote environment presents unique challenges for people
      with chronic conditions, mainly those created by limited health-care services and
      the physical and emotional isolation. Yet, research on how people self-manage
      their chronic conditions in such locations is limited. This study aims to
      contribute to research and clinical practice by describing the ways in which a
      diverse group of rural and remote people with a range of chronic conditions, and
      their unpaid carers, self-manage their conditions. Using semi-structured in-depth
      interviews, data was collected from a sample of 32 participants, residing in one
      of two regions of Australia: Mount Isa/North West region of Queensland and the
      Northern Rivers area of New South Wales. Our findings suggest that although self
      managing in a rural and remote context requires many of the lifestyle changes
      necessary in urban areas, the uniqueness of the rural lifestyle and the limited
      availability of health care results in, at times, creative forms of self
      management. Health-care professionals and policy makers need to be cognisant of
      the ways in which rural and remote residents modify self-management strategies to
      suit their needs, and help them develop self-management plans tailored to the
      realities of their rural environment. 

PMID- 24135050
TI  - Pseudopotential-based studies of electron transport in graphene and graphene
      nanoribbons.
AB  - The theoretical understanding of electron transport in graphene and graphene
      nanoribbons is reviewed, emphasizing the help provided by atomic pseudopotentials
      (self-consistent and empirical) in determining not only the band structure but
      also other fundamental transport parameters such as electron-phonon matrix
      elements and line-edge roughness scattering. Electron-phonon scattering in
      suspended graphene sheets, impurity and remote-phonon scattering in supported and
      gated graphene, electron-phonon and line-edge roughness scattering in armchair
      edge nanoribbons are reviewed, keeping in mind the potential use of graphene in
      devices of the future very large scale integration technology. 

PMID- 24135051
TI  - Defining successful aging: the need to distinguish pathways from outcomes.

PMID- 24135052
TI  - Dysregulation of miR-124-1 predicts favorable prognosis in acute myeloid
      leukemia.
AB  - OBJECTIVE: MicroRNA miR-124 has been suggested as a tumor suppressor for its role
      in inhibiting cell growth, inducing differentiation and promoting apoptosis. The
      present study was aimed to investigate the expression status of miR-124-1 and its
      clinical relevance in patients with acute myeloid leukemia (AML). DESIGNS AND
      METHODS: Real-time quantitative PCR was performed to detect the expression level
      of miR-124-1 in AML patients. The clinical significance of miR-124-1 expression
      in AML was investigated. RESULTS: miR-124-1 underexpression was identified in 30
      (36%) of 83 AML patients. No significant difference could be observed in sex, age
      and blood parameters between the patients with and without miR-124-1
      underexpression. The frequency of miR-124-1 underexpression was higher in the
      patients with t(15;17) than in others (62% versus 30%, P = 0.040). The status of
      miR-124-1 expression was not correlated with the mutations of nine genes (FLT3
      ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). The patients with miR
      124-1 underexpression had borderline longer overall survival and relapse-free
      survival than those without miR-124-1 underexpression (P = 0.052 and 0.045,
      respectively). CONCLUSIONS: These findings suggest that miR-124-1 underexpression
      is a common event and might have a favorable impact on prognosis in AML.

PMID- 24135053
TI  - Reliability and accuracy of real-time visualization techniques for measuring
      school cafeteria tray waste: validating the quarter-waste method.
AB  - Measuring food waste is essential to determine the impact of school interventions
      on what children eat. There are multiple methods used for measuring food waste,
      yet it is unclear which method is most appropriate in large-scale interventions
      with restricted resources. This study examines which of three visual tray waste
      measurement methods is most reliable, accurate, and cost-effective compared with
      the gold standard of individually weighing leftovers. School cafeteria
      researchers used the following three visual methods to capture tray waste in
      addition to actual food waste weights for 197 lunch trays: the quarter-waste
      method, the half-waste method, and the photograph method. Inter-rater and inter
      method reliability were highest for on-site visual methods (0.90 for the quarter
      waste method and 0.83 for the half-waste method) and lowest for the photograph
      method (0.48). This low reliability is partially due to the inability of
      photographs to determine whether packaged items (such as milk or yogurt) are
      empty or full. In sum, the quarter-waste method was the most appropriate for
      calculating accurate amounts of tray waste, and the photograph method might be
      appropriate if researchers only wish to detect significant differences in waste
      or consumption of selected, unpackaged food. 

PMID- 24135054
TI  - Efficacy of repetitive transcranial magnetic stimulation in the prevention of
      relapse of depression: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Depression is a chronic illness that generally requires lifelong
      therapy. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive
      technique with few side effects that has been reported to be useful in the
      treatment of depression. However, no studies to date have evaluated in a
      randomized controlled trial (RCT) the efficacy of rTMS for maintenance treatment
      of depression. METHODS/DESIGN: In this article, we report the design and protocol
      of a randomized, single-blind, placebo-controlled, parallel-group, multicenter
      study in China to evaluate the efficacy of rTMS in the prevention of relapse of
      depressive symptoms. In total, 540 patients, aged 18 to 60 years, diagnosed with
      depression and experiencing an acute exacerbation of depressive symptoms, will be
      enrolled. The study will consist of four phases: a screening/tolerability phase
      of up to 7 days; an open-label, flexible-dose lead-in phase of 8 weeks; an open
      label, fixed-dose stabilization phase of 6 weeks; and a single-blind relapse
      prevention phase of 12 months. During the open-label phase, all patients will be
      treated with venlafaxine. Remitters with Hamilton Rating Scale for Depression
      (HAM-D17) score <=7 will be eligible to enter the single-blind phase and will be
      randomly assigned to one of three groups: group 1 on active rTMS and venlafaxine;
      group 2 on sham rTMS and venlafaxine; and group 3 on venlafaxine alone. Efficacy
      will be evaluated during the study using relapse assessment (time between subject
      randomization to treatment and the first occurrence of relapse). Secondary
      outcome measures will include: symptom changes, measured by the HAM-D17; illness
      severity changes, measured by the Clinical Global Impression of Severity for
      Depression (CGI-S-DEP); and changes in subject functioning, assessed with the
      Personal and Social Performance (PSP)scale. Safety will be assessed throughout
      the study by monitoring of adverse events, clinical laboratory tests,
      electrocardiography (ECG), and measurements of vital signs (temperature, pulse,
      and blood pressure) and weight. Suicidality will be assessed by the Columbia
      Suicide Severity Rating Scale (C-SSRS). DISCUSSION: The result of this trial will
      assess the efficacy of rTMS in the prevention of relapse of symptoms of
      depression by determining whether rTMS in combination with an antidepressant is
      more efficacious than the antidepressant alone for maintenance of the clinical
      response. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01516931.

PMID- 24135055
TI  - Culture promotes transfer of thyroid epithelial cell hyperplasia and
      proliferation by reducing regulatory T cell numbers.
AB  - IFN-gamma(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease,
      thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in
      their water for 7+ mo. TEC H/P can be transferred to IFN-gamma(-/-) SCID mice by
      splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is
      improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN
      gamma(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2
      fold greater than younger (2 mo) mice. During culture, the number of T reg
      decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2
      prior to transfer prevents the decrease of T reg and improves their in vitro
      suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore,
      culturing splenocytes improves transfer of TEC H/P by reducing the number of T
      reg and IL-2 inhibits transfer by preserving T reg number and function. 

PMID- 24135056
TI  - MiR-134-mediated beta1 integrin expression and function in mesenchymal stem
      cells.
AB  - The composition of the hematopoietic stem cell (HSC) niche within the bone marrow
      is highly dynamic, tightly regulated, and of importance for various HSC
      properties. Integrins are important molecules within this niche that influence
      those properties through the interactions of HSCs and mesenchymal stem cells
      (MSCs). Here we investigated the function of miR-134 in integrin regulation in
      MSCs. In MSCs, miR-134 post-transcriptionally regulated beta1 integrin
      expression. This negative regulation of beta1 integrin was mediated by the
      binding of miR-134 to its 3' untranslated region, which contains two conserved
      binding sites for miR-134. The miR-134-mediated silencing of beta1 integrin in
      MSCs was shown by atomic force microscopy to decrease the adhesion of 32D cells
      to MSCs transfected with miR-134. Furthermore, the adhesion of MSCs to
      fibronectin was reduced after transfection with miR-134. MSCs from patients with
      myelodysplastic syndrome (MDS) revealed highly significant miR-134 overexpression
      compared with MSCs from healthy bone marrow donors. MSCs from MDS patients showed
      lower beta1 integrin protein, but not lower mRNA, expression, suggesting post
      transcriptional regulation. The present study demonstrates miR-134-mediated
      negative regulation of beta1 integrin that influences cell adhesion to and of
      MSCs. These results further contribute to our understanding of the complexity of
      MDS. 

PMID- 24135057
TI  - Short-term TNFalpha shedding is independent of cytoplasmic phosphorylation or
      furin cleavage of ADAM17.
AB  - Proteolysis of transmembrane molecules is an irreversible post-translational
      modification enabling autocrine, paracrine and endocrine signaling of many
      cytokines. The pro-inflammatory activities of membrane bound TNFalpha (pro
      TNFalpha) strongly depend on ectodomain shedding mediated by the A Disintegrin
      And Metalloprotease family member ADAM17. Despite the well-documented role of
      ADAM17 in pro-TNFalpha cleavage during inflammation, little is known about its
      regulation. Mitogen-activated protein kinase-induced phosphorylation of the
      ADAM17 cytoplasmic tail has been described to be required for proper activation.
      To address, if pro-TNFalpha shedding depends on cytosolic phosphorylation we
      analyzed ADAM17 mutants lacking the cytoplasmic domain. ADAM17 mediated shedding
      of pro-TNFalpha was induced by PMA, Anisomycin and the phosphatase inhibitors
      Cantharidin and Calyculin A. Deletion of the entire cytoplasmic portion of ADAM17
      abolished furin-dependent proteolytic maturation and pro-TNFalpha cleavage.
      Interestingly, we could exclude that resistance to proconvertase processing is
      the reason for the enzymatic inactivity of ADAM17 lacking the cytoplasmic portion
      as furin-resistant ADAM17 mutants rescued genetic ADAM17 deficiency after mitogen
      activated protein kinase activation. Adding only 6 cytoplasmic amino acids
      completely restored ADAM17 maturation and shedding of pro-TNFalpha as well as of
      both TNF-receptors Finally, we showed that a pro-TNFalpha mutant lacking the
      cytoplasmic portion was also shed from the cell surface. We conclude that pro
      TNFalpha cleavage by its major sheddase ADAM17 does not depend on cytosolic
      phosphorylation and/or interaction. These results have general implications on
      understanding the activation mechanism controlling the activity of ADAM17. 

PMID- 24135058
TI  - Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex.
AB  - Mitochondrial beta-barrel proteins fulfill central functions in the outer
      membrane like metabolite exchange catalyzed by the voltage-dependent anion
      channel (VDAC) and protein biogenesis by the central components of the preprotein
      translocase of the outer membrane (Tom40) or of the sorting and assembly
      machinery (Sam50). The mitochondrial division and morphology protein Mdm10 is
      another essential outer membrane protein with proposed beta-barrel fold, which
      has so far only been found in Fungi. Mdm10 is part of the endoplasmic reticulum
      mitochondria encounter structure (ERMES), which tethers the ER to mitochondria
      and associates with the SAM complex. In here, we provide evidence that Mdm10
      phylogenetically belongs to the VDAC/Tom40 superfamily. Contrary to Tom40 and
      VDAC, Mdm10 exposes long loops towards both sides of the membrane. Analyses of
      single loop deletion mutants of Mdm10 in the yeast Saccharomyces cerevisiae
      reveal that the loops are dispensable for Mdm10 function. Sequences similar to
      fungal Mdm10 can be found in species from Excavates to Fungi, but neither in
      Metazoa nor in plants. Strikingly, the presence of Mdm10 coincides with the
      appearance of the other ERMES components. Mdm10's presence in both unikonts and
      bikonts indicates an introduction at an early time point in eukaryotic evolution.

PMID- 24135059
TI  - Assembly of beta-barrel proteins into bacterial outer membranes.
AB  - Membrane proteins with a beta-barrel topology are found in the outer membranes of
      Gram-negative bacteria and in the plastids and mitochondria of eukaryotic cells.
      The assembly of these membrane proteins depends on a protein folding reaction (to
      create the barrel) and an insertion reaction (to integrate the barrel within the
      outer membrane). Experimental approaches using biophysics and biochemistry are
      detailing the steps in the assembly pathway, while genetics and bioinformatics
      have revealed a sophisticated production line of cellular components that
      catalyze the assembly pathway in vivo. This includes the modular BAM complex,
      several molecular chaperones and the translocation and assembly module (the TAM).
      Recent screens also suggest that further components of the pathway might remain
      to be discovered. We review what is known about the process of beta-barrel
      protein assembly into membranes, and the components of the beta-barrel assembly
      machinery. This article is part of a Special Issue entitled: Protein trafficking
      and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. 

PMID- 24135060
TI  - [Clinical phenotypes and prognosis of antisynthetase syndrome].
AB  - Antisynthetase syndrome (ASS) was first described in 1989 as an inflammatory
      myopathy associated with the presence of specific auto-antibodies, namely the
      anti-tRNA-synthetase antibodies (ASA). To date, the ASA family comprises eight
      different auto-antibodies, among which anti-hystidyl-tRNA-synthetase (anti-Jo1)
      is the most prevalent. In addition to myositis, a constellation of clinical
      features has also been described in ASS, including interstitial lung disease,
      Raynaud's phenomenon, polyarthritis, fever and mechanic's hands. Large variations
      in the distribution and the severity of each of these symptoms are reported from
      one patient to another, and also over the course of the disease. The
      heterogeneity of this autoimmune connective tissue disease has led to
      difficulties in the early identification of patients with a poor outcome (those
      who will require the most intensive treatments). Additionally, very few
      prospective trials have so far compared the efficacy of the different
      immunosuppressive drugs available, and evidence is lacking to help adapting
      therapeutic strategies to all of the different ASS clinical situations. We will
      review the different characteristics of ASS (namely biological, clinical,
      functional, and morphological ASS parameters) that have recently been shown to
      correlate with patients' outcome, our aim being to discuss the usefulness of
      patient stratification for elaborating targeted therapeutic trials for ASS in the
      future.

PMID- 24135061
TI  - [Mycoplasma pneumoniae encephalitis successfully treated by levofloxacin].
AB  - INTRODUCTION: Mycoplasma pneumonia (MP) infection may be associated with several
      neurological complications. Encephalitis, which affects children and rarely young
      adults, is the most frequent. CASE REPORT: A 23-year-old man was admitted for
      pneumonia with encephalitis. Mycoplasma pneumoniae infection was documented by
      serology, and polymerase chain reaction in the cerebrospinal fluid. Despite
      serious initial presentation, outcome was favourable with levofloxacin treatment.
      CONCLUSION: MP infection should be considered as a potential aetiology in acute
      encephalitis in young people and in individuals with respiratory symptoms.
      Antibiotic therapy (fluoroquinolones or macrolides) should be used if MP is
      strongly suspected or in case of severe acute meningo-encephalitis.

PMID- 24135062
TI  - Determination of stilbenes and resorcylic acid lactones in bovine, porcine and
      poultry muscle tissue by liquid chromatography-negative ion electrospray mass
      spectrometry and QuEChERS for sample preparation.
AB  - Liquid chromatography tandem mass spectrometry method was developed and validated
      to confirm of resorcylic acid lactones: zeranol, taleranol, zearalanone,
      zearalenone, alpha and beta-zearalenol and stilbenes in muscle tissue. The
      compounds were analyzed by LC-MS/MS QTrap 5500 apparatus in negative ionization
      mode. Chromatographic separation on Poroshell 120-EC C18 (150mm*2.1mm, 2.7MUm)
      column was achieved at 45 degrees C using isocratic elution of mobile phase -
      methanol/water (65:35, v/v). For the treatment of tissue samples prior to
      analysis, QuEChERS method was applied based on the extraction of analytes from
      muscle samples with ethyl acetate, separation of the aqueous and organic phases
      with application of magnesium sulphate and sodium acetate, the purification of
      the extract obtained by dispersive SPE with the use of sorbent C18, PSA and
      magnesium sulphate. The method was validated in accordance with the Commission
      Decision 2002/657/EC. Good recoveries were obtained (from 83% to 115%) as well as
      acceptable within-lab reproducibility (<22%). The values of the decision limit
      CCalpha and the detection capability CCbeta for individual compounds are found to
      be below the recommended concentration set at 1MUgkg(-1) and not exceed
      0.23MUgkg(-1) and 0.39MUgkg(-1), respectively. The elaborated method meets the
      criteria for confirmatory methods and is used in the official control of
      hormones. 

PMID- 24135063
TI  - Purification of a mannose-binding lectin Pinellia ternata agglutinin and its
      induction of apoptosis in Bel-7404 cells.
AB  - A novel high-throughput purification method for a monocot mannose-binding lectin,
      Pinellia ternata agglutinin (PTA), from tubers of P. ternata was established by
      mannose-Sephrose 4B affinity chromatography. The total protein was extracted from
      tubers of P. ternata using phosphate buffered saline (PBS) buffer. The extracted
      total protein was precipitated completely at 65% ammonium sulfate saturation and
      dissolved in different concentrations of NaCl solution to activate its binding
      affinity toward the column. PTA was bound to the affinity column by loading of
      the total protein into the column and elution using PBS buffer. The maximum
      purification yield (35.5mg/g) was obtained when PTA was treated with 25% (w/v)
      NaCl solution, and the purity of PTA analyzed by SDS-PAGE was ~97%. The
      agglutination property of purified PTA was confirmed by mouse erythrocytes, which
      indicates its biological function. Nuclear staining assay and DNA fragmentation
      demonstrated that PTA could induce apoptosis of Bel-7404 cells, which further
      demonstrates its biological and pharmacological activities. Induction of
      apoptosis in the human tumor Bel-7404 cell line by PTA indicates its possible use
      in cancer therapy. The present investigation reports a significantly improved
      isolation method to obtain highly purified mannose-binding plant lectin proteins.
      The proposed method has great potential for industrial application because of its
      advantages, which include rapid isolation, high purity, high yield, low cost, and
      minimal requirement of chemical materials. 

PMID- 24135064
TI  - iWitness pollution map: crowdsourcing petrochemical accident research.
AB  - Community members living near any one of Louisiana's 160 chemical plants or
      refineries have always said that accidents occurring in these petrochemical
      facilities significantly impact their health and safety. This article reviews the
      iWitness Pollution Map tool and Rapid Response Team (RRT) approach led by the
      Louisiana Bucket Brigade, an environmental nonprofit group, and their
      effectiveness in documenting these health and safety impacts during petrochemical
      accidents. Analysis of a January 2013 RRT deployment in Chalmette, LA, showed
      increased documentation of current petrochemical accidents and suggested
      increased preparedness to report future accidents. The RRT model encourages
      government response and enforcement agencies to integrate with organized
      community groups to fully document the impacts during ongoing accidents, lead a
      more timely response to the accident, and prevent future accidents from
      occurring. 

PMID- 24135066
TI  - "I need my nurse!" Nurses and the criminalization of HIV in North America.

PMID- 24135067
TI  - Comparison of bipolar versus monopolar extraoperative electrical cortical
      stimulation mapping in patients with focal epilepsy.
AB  - OBJECTIVE: Extraoperative cortical stimulation (CS) for mapping of eloquent
      cortex in patients prior to epilepsy surgery is not standardized across centres.
      Two different techniques are in use, referred to as bipolar and monopolar CS. We
      compared the ability of bipolar versus monopolar CS to identify eloquent cortex
      and their safety profile in patients undergoing subdural EEG recordings. METHODS:
      Five patients undergoing intracranial EEG recordings and extraoperative CS.
      Systematic comparison of stimulus parameters, clinical signs and afterdischarges
      of bipolar versus monopolar CS. RESULTS: Bipolar CS requires less stimulation
      current but is more time consuming and more likely to produce afterdischarges
      when compared to monopolar CS. None of the stimulations elicited seizures. The
      area defined as eloquent by either bipolar or monopolar CS reveals only minor
      discordances, involving mainly the outer row and edge of the electrode array
      producing clinical signs with monopolar CS only. Qualitatively, bi- and monopolar
      CS reproduced similar movements and types of muscle contractions. CONCLUSIONS:
      Bipolar and monopolar CS are safe procedures identifying similar cortical areas
      as eloquent, although monopolar cortical stimulation is less time consuming.
      SIGNIFICANCE: Findings advocate the use of monopolar CS in a clinical setting.

PMID- 24135068
TI  - Branchio-otic syndrome caused by a genomic rearrangement: clinical findings and
      molecular cytogenetic studies in a patient with a pericentric inversion of
      chromosome 8.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominantly inherited
      developmental disorder, which is characterized by anomalies of the ears, the
      branchial arches and the kidneys. It is caused by mutations in the genes
      EYA1,SIX1 and SIX5. Genomic rearrangements of chromosome 8 affecting the EYA1
      gene have also been described. Owing to this fact, methods for the identification
      of abnormal copy numbers such as multiplex ligation-dependent probe amplification
      (MLPA) have been introduced as routine laboratory techniques for molecular
      diagnostics of BOR syndrome. The advantages of these techniques are clear
      compared to standard cytogenetic and array approaches as well as Southern blot.
      MLPA detects deletions or duplications of a part or the entire gene of interest,
      but not balanced structural aberrations such as inversions and translocations.
      Consequently, disruption of a gene by a genomic rearrangement may escape
      detection by a molecular genetic analysis, although this gene interruption
      results in haploinsufficiency and, therefore, causes the disease. In a patient
      with clinical features of BOR syndrome, such as hearing loss, preauricular
      fistulas and facial dysmorphisms, but no renal anomalies, neither sequencing of
      the 3 genes linked to BOR syndrome nor array comparative genomic hybridization
      and MLPA were able to uncover a causative mutation. By routine cytogenetic
      analysis, we finally identified a pericentric inversion of chromosome 8 in the
      affected female. High-resolution multicolor banding confirmed the chromosome 8
      inversion and narrowed down the karyotype to 46,XX,inv(8)(p22q13). By applying
      fluorescence in situ hybridization, we narrowed down both breakpoints on
      chromosome 8 and found the EYA1 gene in q13.3 to be directly disrupted. We
      conclude that standard karyotyping should not be neglected in the genetic
      diagnostics of BOR syndrome or other Mendelian disorders, particularly when
      molecular testing failed to detect any causative alteration in patients with a
      convincing phenotype.

PMID- 24135069
TI  - Placental vascular dysfunction, fetal and childhood growth, and cardiovascular
      development: the generation R study.
AB  - BACKGROUND: Suboptimal fetal nutrition may influence early growth and
      cardiovascular development. We examined whether umbilical and uterine artery
      resistance indices, as measures of feto-placental and utero-placental vascular
      function, respectively, are associated with fetal and childhood growth and
      cardiovascular development. METHODS AND RESULTS: This study was embedded in a
      population-based prospective cohort study among 6716 mothers and their children.
      Umbilical artery pulsatility index and uterine artery resistance index and fetal
      growth were measured in third trimester. Childhood growth was repeatedly assessed
      from birth to the age of 6 years. We measured body fat distribution, left
      ventricular mass, and blood pressure at the age of 6 years. Higher third
      trimester umbilical and uterine artery vascular resistance were associated with
      lower fetal length and weight growth in third trimester resulting in a smaller
      size at birth among boys and girls (P values < 0.05). These differences in length
      and weight growth became smaller from the age of 6 months onwards, but were still
      present at the age of 6 years. Higher third trimester umbilical artery vascular
      resistance, but not uterine artery vascular resistance, was associated with
      higher childhood body mass index, total fat mass, android/gynoid fat mass ratio,
      and systolic blood pressure, and with a lower left ventricular mass (P
      values<0.05). These associations were not explained by birth weight. Stronger
      associations tended to be present among girls as compared with boys. CONCLUSIONS:
      Higher third trimester feto-placental vascular resistance, but not utero
      placental vascular resistance, was associated with slower fetal growth rates and
      cardiovascular adaptations in childhood.

PMID- 24135070
TI  - Linking intrauterine growth restriction and blood pressure: insight into the
      human origins of cardiovascular disease.

PMID- 24135071
TI  - Prenatal diagnosis, birth location, surgical center, and neonatal mortality in
      infants with hypoplastic left heart syndrome.
AB  - BACKGROUND: Most studies have not demonstrated improved survival after prenatal
      diagnosis of critical congenital heart disease, including hypoplastic left heart
      syndrome (HLHS). However, the effect of delivery near a cardiac surgical center
      (CSC), the recommended action after prenatal diagnosis, on HLHS mortality has
      been poorly investigated. METHODS AND RESULTS: Using Texas Birth Defects Registry
      data, 1999 through 2007, which monitored >3.4 million births, we investigated the
      association between distance (calculated driving time) from birth center to CSC
      and neonatal mortality in 463 infants with HLHS. Infants with extracardiac birth
      defects or genetic disorders were excluded. The associations between prenatal
      diagnosis, CSC HLHS volume, and mortality were also examined. Neonatal mortality
      in infants born <10 minutes from a CSC was 21.0%, 10 to 90 minutes 25.2%, and >90
      minutes 39.6% (P for trend <0.001). Prenatal diagnosis alone was not associated
      with improved survival (P=0.14). In multivariable analysis, birth >90 minutes
      from a CSC remained associated with increased mortality (odds ratio, 2.03; 95%
      confidence interval, 1.19-3.45), compared with <10 minutes. In subanalysis, birth
      >90 minutes from a CSC was associated with higher pretransport mortality (odds
      ratio, 6.69; 95% confidence interval, 2.52-17.74) and birth 10 to 90 minutes with
      higher presurgical mortality (odds ratio, 4.45; 95% confidence interval, 1.17
      17.00). Higher surgical mortality was associated with lower CSC HLHS volume (odds
      ratio per 10 patients, 0.88; 95% confidence interval, 0.84-0.91). CONCLUSIONS:
      Infants with HLHS born far from a CSC have increased neonatal mortality, and most
      of this mortality is presurgical. Efforts to improve prenatal diagnosis of HLHS
      and subsequent delivery near a large volume CSC may significantly improve
      neonatal HLHS survival.

PMID- 24135072
TI  - Doing the same thing over and over, yet expecting different results.

PMID- 24135073
TI  - NSAID-induced enteropathy: are the currently available selective COX-2 inhibitors
      all the same?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal
      damage, but the underlying mechanisms remain poorly understood. The present study
      investigated the effects of celecoxib, etoricoxib, indomethacin, and diclofenac
      on small bowel integrity in rats. Male rats were treated orally with test drugs
      for 14 days. Animals were processed for assessment of blood hemoglobin levels and
      hepatic mitochondrial functions, microscopic evaluation of small intestinal
      damage, Western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2)
      expression, and assay of malondialdehyde (MDA), myeloperoxidase (MPO), and
      prostaglandin E2 (PGE2) levels in small intestine. Indomethacin and diclofenac
      decreased blood hemoglobin levels, whereas etoricoxib and celecoxib were without
      effects. Celecoxib caused a lower degree of intestinal damage in comparison with
      the other test drugs. Indomethacin and diclofenac, but not etoricoxib or
      celecoxib, reduced intestinal PGE2 levels. Test drugs did not modify intestinal
      COX-1 expression, although they enhanced COX-2, with the exception of celecoxib,
      which downregulated COX-2. Indomethacin, diclofenac, and etoricoxib altered
      mitochondrial respiratory parameters, although celecoxib was without effects.
      Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and
      ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters,
      whereas in the ileum, etoricoxib, but not celecoxib, increased both MDA and MPO
      levels. These findings suggest that nonselective NSAIDs and etoricoxib can induce
      enteropathy through a topic action, whereas celecoxib lacks relevant detrimental
      actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs and the
      related effects on prostaglandin production do not appear to play a major role in
      the pathogenesis of enteropathy. 

PMID- 24135075
TI  - Dopamine and lipophilic derivates protect cardiomyocytes against cold
      preservation injury.
AB  - Donor heart allografts are extremely susceptible to prolonged static cold
      storage. Because donor treatment with low-dose dopamine improves clinical outcome
      after heart transplantation, we tested the hypothesis that dopamine and its
      lipophilic derivate, N-octanoyl dopamine (NOD), protect cardiomyocytes from cold
      storage injury. Neonatal rat cardiomyocytes were treated with dopamine or NOD or
      left untreated and subsequently subjected to static cold storage (8-12 hours).
      Dopamine- and NOD-treated cardiomyocytes displayed a better viability compared
      with untreated cells after hypothermia. In untreated cardiomyocytes, cell damage
      was reflected by lactate dehydrogenase (LDH) release and a decrease in
      intracellular ATP. NOD was approximately 20-fold more potent than dopamine.
      Similarly to cardiomyocytes in vitro, rat hearts perfused with NOD before
      explantation showed significantly lower LDH release after static cold storage.
      ATP regeneration and spontaneous contractions after cold storage and rewarming
      only occurred in treated cardiomyocytes. Hypothermia severely attenuated
      isoprenaline-induced cAMP formation in control but not in dopamine- or NOD
      treated cells. Esterified derivates of NOD with redox potential and lipophilic
      side chains reduced cell damage during cold storage similarly to NOD. In contrast
      to dopamine, neither NOD nor its derivates induced a significant beta
      adrenoceptor-mediated elevation of cellular cAMP levels. The beta1-adrenoceptor
      antagonist atenolol and D1/D2 receptor antagonist fluphenazine had no impact on
      the protective effect of NOD or dopamine. We conclude that dopamine as well as
      NOD treatment mitigates cold preservation injury to cardiomyocytes. The
      beneficial effects are independent of beta-adrenoceptor or dopaminergic receptor
      stimulation but correlate with redox potential and lipophilic properties. 

PMID- 24135074
TI  - A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a
      modulator of cardiovascular nitric oxide.
AB  - PD 404182 [6H-6-imino-(2,3,4,5-tetrahydropyrimido)[1,2-c]-[1,3]benzothiazine], a
      heterocyclic iminobenzothiazine derivative, is a member of the Library of
      Pharmacologically Active Compounds (LOPAC) that is reported to possess
      antimicrobial and anti-inflammatory properties. In this study, we used
      biochemical assays to screen LOPAC against human dimethylarginine
      dimethylaminohydrolase isoform 1 (DDAH1), an enzyme that physiologically
      metabolizes asymmetric dimethylarginine (ADMA), an endogenous and competitive
      inhibitor of nitric oxide (NO) synthase. We discovered that PD 404182 directly
      and dose-dependently inhibits DDAH. Moreover, PD 404182 significantly increased
      intracellular levels of ADMA in cultured primary human vascular endothelial cells
      (ECs) and reduced lipopolysaccharide-induced NO production in these cells,
      suggesting its therapeutic potential in septic shock-induced vascular collapse.
      In addition, PD 404182 abrogated the formation of tube-like structures by ECs in
      an in vitro angiogenesis assay, indicating its antiangiogenic potential in
      diseases characterized by pathologically excessive angiogenesis. Furthermore, we
      investigated the potential mechanism of inhibition of DDAH by this small molecule
      and found that PD 404182, which has striking structural similarity to ADMA, could
      be competed by a DDAH substrate, suggesting that it is a competitive inhibitor.
      Finally, our enzyme kinetics assay showed time-dependent inhibition, and our
      inhibitor dilution assay showed that the enzymatic activity of DDAH did not
      recover significantly after dilution, suggesting that PD 404182 might be a
      tightly bound, covalent, or an irreversible inhibitor of human DDAH1. This
      proposal is supported by mass spectrometry studies with PD 404182 and
      glutathione. 

PMID- 24135076
TI  - The immature human ovary shows loss of abnormal follicles and increasing follicle
      developmental competence through childhood and adolescence.
AB  - STUDY QUESTION: Do the ovarian follicles of children and adolescents differ in
      their morphology and in vitro growth potential from those of adults? SUMMARY
      ANSWER: Pre-pubertal ovaries contained a high proportion of morphologically
      abnormal non-growing follicles, and follicles showed reduced capacity for in
      vitro growth. WHAT IS KNOWN ALREADY: The pre-pubertal ovary is known to contain
      follicles at the early growing stages. How this changes over childhood and
      through puberty is unknown, and there are no previous data on the in vitro growth
      potential of follicles from pre-pubertal and pubertal girls. STUDY DESIGN, SIZE,
      DURATION: Ovarian biopsies from five pre-pubertal and seven pubertal girls and 19
      adult women were analysed histologically, cultured in vitro for 6 days, with
      growing follicles then isolated and cultured for a further 6 days.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian biopsies were obtained from
      girls undergoing ovarian tissue cryopreservation for fertility preservation, and
      compared with biopsies from adult women. Follicle stage and morphology were
      classified. After 6 days in culture, follicle growth initiation was assessed. The
      growth of isolated secondary follicles was assessed over a further 6 days,
      including analysis of oocyte growth. MAIN RESULTS AND THE ROLE OF CHANCE: Pre
      pubertal ovaries contained a high proportion of abnormal non-growing follicles
      (19.4 versus 4.85% in pubertal ovaries; 4004 follicles analysed; P = 0.02)
      characterized by indistinct germinal vesicle membrane and absent nucleolus.
      Follicles with this abnormal morphology were not seen in the adult ovary. During
      6 days culture, follicle growth initiation was observed at all ages; in pre
      pubertal samples there was very little development to secondary stages, while
      pubertal samples showed similar growth activation to that seen in adult tissue
      (pubertal group: P = 0.02 versus pre-pubertal, ns versus adult). Isolated
      secondary follicles were cultured for a further 6 days. Those from pre-pubertal
      ovary showed limited growth (P < 0.05 versus both pubertal and adult follicles)
      and no change in oocyte diameter over that period. Follicles from pubertal
      ovaries showed increased growth; this was still reduced compared with follicles
      from adult women (P < 0.05) but oocyte growth was proportionate to follicle size.
      LIMITATIONS, REASONS FOR CAUTION: These data derive from only a small number of
      ovarian biopsies, although large numbers of follicles were analysed. It is
      unclear whether the differences between groups are related to puberty, or just
      age. WIDER IMPLICATIONS OF THE FINDINGS: These findings show that follicles from
      girls of all ages can be induced to grow in vitro, which has important
      implications for some patients who are at high risk of malignant contamination of
      their ovarian tissue. The reduced growth of isolated follicles indicates that
      there are true intrafollicular differences in addition to potential differences
      in their local environment, and that there are maturational processes occurring
      in the ovary through childhood and adolescence, which involve the loss of
      abnormal follicles, and increasing follicle developmental competence. STUDY
      FUNDING/COMPETING INTEREST(S): Funded by MRC grants G0901839 and G1100357. No
      competing interests.

PMID- 24135077
TI  - Beneficial effect of directional freezing on in vitro viability of cryopreserved
      sheep whole ovaries and ovarian cortical slices.
AB  - STUDY QUESTION: Does directional freezing improve the structural and functional
      integrity of ovarian fragments compared with conventional slow freezing and to
      whole ovary cryopreservation? SUMMARY ANSWER: Compared with slow freezing, the
      use of directional freezing significantly improves all structural and functional
      parameters of ovarian fragments assessed in vitro and, overall, whole ovaries
      were better preserved than ovarian fragments. WHAT IS KNOWN ALREADY: Directional
      freezing has been developed to provide an alternative way to cryopreserve large
      biological samples and it is known to improve the structural and functional
      integrity of whole ovaries. Conventional slow freezing of ovarian fragments is
      the procedure more widely used in clinical settings but it causes substantial
      structural damage that limits the functional period after transfer back into the
      patient. STUDY DESIGN, SIZE, DURATION: We performed a 2 * 2 factorial design
      experiment on a total of 40 sheep ovaries, divided into four groups (n = 10
      ovaries per group): (i) directional freezing of whole ovary (DFwo); (ii)
      directional freezing of ovarian fragments (DFof); (iii) conventional freezing of
      whole ovary (CFwo); (iv) conventional freezing of ovarian fragments (CFof). An
      additional eight ovaries were used as fresh controls. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Ewe ovaries were randomly assigned to one of the experimental
      groups and frozen accordingly. Upon thawing, ovarian tissue was examined
      morphologically and cultured in vitro for 7 days. Samples were analyzed for cell
      proliferation and apoptosis, for DNA damage and repair activity, and for the
      presence of a panel of heat shock proteins (HSPs) by immunohistochemistry. MAIN
      RESULTS AND THE ROLE OF CHANCE: Most studied parameters were significantly
      improved (P < 0.05) in all samples cryopreserved with directional compared with
      slow freezing. The proportion of primordial follicles, which developed to the
      primary stage in whole ovaries (53 +/- 1.7%) and in ovarian fragments (44 +/-
      1.8%) cryopreserved with directional freezing, was greater than with slow frozen
      whole ovaries (6 +/- 0.5%, P = 0.001) or fragments (32 +/- 1.5%, P = 0.004).
      After 7 days of culture, cell proliferation in DFwo (28 +/- 0.73%) was the
      highest of all groups (P < 0.05) followed by DFof (23 +/- 0.81%), CFof (20 +/-
      0.79%) and CFwo (9 +/- 0.85%). Directional freezing also resulted in a better
      preservation of the cell capacity to repair DNA damage compared with slow
      freezing both in whole ovaries and ovarian fragments. Apoptosis and HSP protein
      levels were significantly increased only in the CFwo group. Direct comparison
      demonstrated that, overall, DFwo had better parameters than DFof and was no
      different from the fresh controls. LIMITATIONS, REASONS FOR CAUTION: The study is
      limited to an in vitro evaluation and uses sheep ovaries, which are smaller than
      human ovaries and therefore may withstand the procedures better. WIDER
      IMPLICATIONS OF THE FINDINGS: Improved integrity of ovarian morphology may
      translate to improved outcomes after transplantation. Alternatively, the
      particularly good preservation of whole ovaries suggests they could provide a
      source of ovarian follicles for in vitro culture in those cases when the presence
      of malignant cells poses a substantial risk for the patient. STUDY
      FUNDING/COMPETING INTEREST(S): Supported by: Associazione Italiana per la Ricerca
      sul Cancro (AIRC) IG 10376, Carraresi Foundation and by Legge 7 Regione Autonoma
      Sardegna (R.A.S). There are no conflicts of interest.

PMID- 24135078
TI  - Rituximab in systemic lupus erythematosus: an updated systematic review and meta
      analysis.
AB  - The wide spectrum of clinical manifestations and high relapse rate represent a
      therapeutic challenge in systemic lupus erythematosus (SLE). Observational
      studies suggested efficacy of rituximab (RTX), a B-cell-targeting antibody, to
      control the activity of SLE. Two randomized trials controlled by placebo did not
      prove the superiority of RTX when used in addition to conventional treatment in
      nonrenal (EXPLORER) and renal (LUNAR) lupus. A systematic review of studies
      exploring the efficacy of RTX in SLE patients was conducted. The pooled
      percentages of response were assessed. Thirty studies with 1243 patients were
      analyzed. In studies using the British Isles Lupus Assessment Group (BILAG), the
      complete response (CR) rate was 46.7% (95% CI 36.8%-56.8%) and the partial
      response (PR) was 37.9% (95% CI 30.6%-45.8%). With the Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI), the CR was 56.6% (95% CI 32.4%
      78.1%) and the PR was 30.9% (95% CI 8.9%-46%). In renal lupus the CR was 36.1%
      (95% CI 25.2%-48.6%); PR was 37.4% (95% CI 28.5%-47.3%). In EXPLORER, CR was
      12.4% and PR was 17.2%; in LUNAR CR was 26.4% and PR was 30.6%, in both cases not
      different from controls. Assessment and standardization of SLE response to
      treatment remain a challenge. The discrepancy in the perceived efficacy of RTX
      between controlled and observational studies reflects the heterogeneity of lupus
      and stringency in criteria of response. Further randomized trials focusing on
      selected SLE manifestations and using composite response indices are warranted. 

PMID- 24135079
TI  - Depression in systemic lupus erythematosus, dependent on or independent of
      severity of disease.
AB  - OBJECTIVES: To estimate the prevalence of depression in subjects with systemic
      lupus erythematosus (SLE) in relation to the general population and to unravel
      the relation between depression and SLE disease characteristics. METHODS: One
      hundred and two subjects with SLE (mean age 44.4 years) were studied using the
      Beck Depression Inventory (BDI) score to estimate the prevalence of depression.
      The BDI scores in subjects with SLE were compared with BDI scores from a pan
      European population based study (Outcome in Depression International Network
      (ODIN) study, n = 7934), i.e. the general population. RESULTS: The mean BDI score
      was higher in SLE subjects (10.1 points) compared with the BDI scores derived
      from the general population (10.1 versus 5.6 points, respectively, p < 0.001).
      This corresponds to a prevalence of depression of 16.6% and 6.7%, respectively.
      There was no association between disease activity or organ damage and BDI scores
      in subjects with SLE (p > 0.1). Only 7% of SLE subjects with high BDI scores used
      antidepressants. CONCLUSION: The mean BDI score and prevalence of depression are
      significantly higher in SLE subjects compared with the general population. No
      association was found between SLE disease characteristics and BDI scores. The
      number of depressed SLE subjects treated with antidepressants is low, suggesting
      inadequate recognition and treatment of depression in SLE.

PMID- 24135080
TI  - The effect of acute physical exercise on cytokine levels in patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: Acute exercise increases IL-6, IL-10 and TNF-alpha levels in healthy
      subjects. There is no study evaluating the effect of exercise on cytokines level
      in systemic lupus erythematosus (SLE) patients. OBJECTIVE: Our aim was to assess
      IL-10, IL-6 and TNF-alpha levels at baseline and after acute physical exercise in
      patients with SLE. METHODS: In total, 27 female SLE patients and 30 healthy
      controls were evaluated. Serum levels of IL-10, IL-6 and TNF-alpha at baseline
      and soon after the ergospirometric test were measured by ELISA test. Student's t
      tests and Mann-Whitney test were used for intra- and inter-group comparisons; p
      values <0.05 were considered significant. RESULTS: Patients with SLE presented
      worse ergospirometric parameters compared with controls: VO2max (25.78 +/- 5.51
      vs. 32.74 +/- 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 +/- 12.36
      vs. 185.15 +/- 2.07 bpm, p = 0.001); maximum ventilation (65.51 +/- 15.68 vs.
      80.48 +/- 18.98 l/min, p = 0.001) and maximum speed (7.70 +/- 1.24 vs. 9.40 +/-
      1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6
      (2.38 +/- 1.70 vs. 1.71 +/- 0.29 pg/ml, p = 0.035) and IL-10 (1.09 +/- 1.55 vs.
      0.30 +/- 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls
      increased IL-6 level (1.71 +/- 0.29 vs. 2.01 +/- 0.27 pg/ml, p = 0.003) without
      change in IL-10 and TNF-alpha levels. However, no significant change in cytokine
      levels was observed in SLE patients after acute exercise. CONCLUSION: This is the
      first study evaluating the effect of acute exercise on cytokine levels in
      patients with SLE. In contrast to healthy controls, acute physical exercise did
      not increase the levels of IL-6 in patients with SLE, and seems to be safe in
      those patients with inactive or mild active disease.

PMID- 24135081
TI  - Professional relationships.

PMID- 24135082
TI  - Allogeneic mesenchymal stem cell infusion for the stabilization of focal
      segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is the most frequent acquired renal
      condition resulting in end stage kidney disease in children. We describe a cell
      therapy treatment with human allogeneic bone marrow mesenchymal stem cells (MSC)
      in a 13-year-old patient developing recurrent FSGS after renal transplantation,
      which was not responding to conventional therapy. This treatment relied on the
      following measurements:clinical and laboratory evaluation of renal function,
      proteome array, biopsy, short tandem repeat assay. Before MSC treatment, the
      patient needed weekly plasmapheresis to achieve proteinuria-to-creatininuria
      ratio below 5. After three MSC infusions without adverse events, the patient has
      a stable renal function and the proteinuria target was reached without
      plasmapheresis. In addition, some circulating inflammatory factors decreased and
      their levels were still low after one year. This is the first report of an MSC
      treatment in an FSGS patient. Even though different factors may have contributed
      to the clinical results, after MSC infusion a stable reduction in the serum level
      of several inflammatory factors has been registered and the patient does not need
      anymore plasmapheresis to keep proteinuria under control. In addition, this
      encouraging single case let us identify some putative efficacy biomarkers that
      could be of clinical interest in chronic kidney diseases. 

PMID- 24135084
TI  - Brown bear sperm double freezing: Effect of elapsed time and use of
      PureSperm((r)) gradient between freeze-thaw cycles.
AB  - The use of sexed spermatozoa has great potential to captive population management
      in endangered wildlife. The problem is that the sex-sorting facility is a long
      distance from the semen collection place and to overcome this difficulty two
      freeze-thaw cycles may be necessary. In this study, effects of refreezing on
      brown bear electroejaculated spermatozoa were analyzed. We carried out two
      experiments: (1) to assess the effects of the two freezing-thawing cycles on
      sperm quality and to analyze three different elapsed times between freezing
      thawing cycles (30, 90 and 180 min), and (2) to analyze the use of PureSperm
      between freezing-thawing cycles to select a more motile and viable sperm
      subpopulation which better survived first freezing. The motility, viability and
      undamaged acrosomes were significantly reduced after the second thawing respect
      to first thawing into each elapsed time group, but the elapsed times did not
      significantly affect the viability and acrosome status although motility was
      damaged. Our results with the PureSperm gradient showed higher values of
      viability in freezability of select sample (pellet) respect to the rest of the
      groups and it also showed a significant decrease in the number of acrosome
      damaged. In summary, the double freezing of bear semen selected by gradient
      centrifugation is qualitatively efficient, and thus could be useful to carry out
      a sex-sorting of frozen-thawed bear spermatozoa before to send the cryopreserved
      sample to a biobank. Given the low recovery of spermatozoa after applying a
      selection gradient, further studies will be needed to increase the recovery rate
      without damaging of the cell quality.

PMID- 24135083
TI  - A review of neuroimaging findings of apathy in Alzheimer's disease.
AB  - BACKGROUND: Apathy is one of the most frequent "behavioral and psychological
      signs and symptoms of dementia" (BPSD) encountered in Alzheimer's disease (AD).
      There is a growing interest in the early diagnosis of apathetic elderly patients
      in the community since apathy has been associated with reduced daily functioning,
      caregiver distress, and poor outcome. The generalization of neuroimaging
      techniques might be able to offer help in this domain. METHODS: Within this
      context we conducted an extensive electronic search from the databases included
      in the National Library of Medicine as well as PsychInfo and Google Scholar for
      neuroimaging findings of apathy in AD. RESULTS: Neuroimaging findings lend
      support to the notion that frontal-subcortical networks are involved in the
      occurrence of apathy in AD. CONCLUSIONS: Longitudinal studies comparing patients
      and normal individuals might allow us to infer on the association between apathy
      and neurodegenerative diseases and what can brain imaging markers tell us about
      the characterization of this association, thus revealing disease patterns,
      helping to distinguish clinically distinct cognitive syndromes, and allowing
      predictions.

PMID- 24135085
TI  - Mothers After Gestational Diabetes in Australia Diabetes Prevention Program
      (MAGDA-DPP) post-natal intervention: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is defined as glucose intolerance
      with its onset or first recognition during pregnancy. Post-GDM women have a life
      time risk exceeding 70% of developing type 2 diabetes mellitus (T2DM). Lifestyle
      modifications reduce the incidence of T2DM by up to 58% for high-risk
      individuals. METHODS/DESIGN: The Mothers After Gestational Diabetes in Australia
      Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial aiming
      to assess the effectiveness of a structured diabetes prevention intervention for
      post-GDM women. This trial has an intervention group participating in a diabetes
      prevention program (DPP), and a control group receiving usual care from their
      general practitioners during the same time period. The 12-month intervention
      comprises an individual session followed by five group sessions at two-week
      intervals, and two follow-up telephone calls. A total of 574 women will be
      recruited, with 287 in each arm. The women will undergo blood tests,
      anthropometric measurements, and self-reported health status, diet, physical
      activity, quality of life, depression, risk perception and healthcare service
      usage, at baseline and 12 months. At completion, primary outcome (changes in
      diabetes risk) and secondary outcome (changes in psychosocial and quality of life
      measurements and in cardiovascular disease risk factors) will be assessed in both
      groups. DISCUSSION: This study aims to show whether MAGDA-DPP leads to a
      reduction in diabetes risk for post-GDM women. The characteristics that predict
      intervention completion and improvement in clinical and behavioral measures will
      be useful for further development of DPPs for this population. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTRN
      12610000338066.

PMID- 24135086
TI  - Inconsistent condom use among HIV-positive women in the "Treatment as Prevention
      Era": data from the Italian DIDI study.
AB  - INTRODUCTION: Translation of the evidence regarding the protective role of highly
      active antiretroviral therapy (HAART) on HIV sexual transmission rates into
      sexual behaviour patterns of HIV-infected subjects remains largely unexplored.
      This study aims to describe frequency of self-reported condom use among women
      living with HIV in Italy and to investigate the variables associated with
      inconsistent condom use (ICU). METHODS: DIDI (Donne con Infezione Da HIV) is an
      Italian multicentre study based on a questionnaire survey performed during
      November 2010 and February 2011. Women-reported frequency of condom use was
      dichotomized in "always" versus "at times"/"never" (ICU). RESULTS: Among 343
      women, prevalence of ICU was 44.3%. Women declared a stable partnership with an
      HIV-negative (38%) and with an HIV-positive person (43%), or an occasional sexual
      partner (19%). Among the 194 women engaged in a stable HIV-negative or an
      occasional partnership, 51% reported fear of infecting the partner. Nonetheless,
      43% did not disclose HIV-positive status. Less than 5% of women used
      contraceptive methods other than condoms. At multivariable analysis, variables
      associated with ICU in the subgroup of women with a stable HIV-negative or an
      occasional HIV-unknown partner were: having an occasional partner (AOR 3.51, 95%
      confidence interval [CI] 1.44-8.54, p=0.005), and reporting fear of infecting the
      sexual partner (AOR 3.20, 95% CI 1.43-7.16, p=0.004). Current use of HAART
      together with virological control in plasma level did not predict ICU after
      adjusting for demographic, behavioural and HIV-related factors. With regard to
      socio-demographic factors, lower education was the only variable significantly
      associated with ICU in the multivariate analysis (AOR 2.27, 95% CI 1.07-4.82,
      p=0.03). No association was found between high adherence to HAART and ICU after
      adjusting for potential confounders (AOR 0.89, 95% CI 0.39-2.01, p=0.78).
      CONCLUSIONS: Currently in Italy, the use of HAART with undetectable HIV RNA in
      plasma as well as antiretroviral adherence is not associated with a specific
      condom use pattern in women living with HIV and engaged with a sero-discordant or
      an HIV-unknown partner. This might suggest that the awareness of the protective
      role of antiretroviral treatment on HIV sexual transmission is still limited
      among HIV-infected persons, at least in this country.

PMID- 24135087
TI  - Diurnal postprandial responses to low and high glycaemic index mixed meals.
AB  - BACKGROUND & AIMS: Glycaemic index testing is conducted in the morning, however
      postprandial glycaemia has a diurnal rhythm. The study aimed to evaluate the
      effect of glycaemic index on glucose tolerance at different times during the day.
      METHODS: A randomised controlled crossover study was conducted in ten healthy
      participants after a standardised premeal and eight hour fast. Low (37) and high
      glycaemic index (73) meals, matched for energy, available carbohydrate, protein
      and fat, were consumed at 08:00 h and 20:00 h. Blood samples were taken for 2 h
      postprandially. RESULTS: Postprandial glucose area under curve showed effect with
      time of day after both meals (Low p < 0.001, High p = 0.003), and a trend (p =
      0.06) to higher glycaemic responses in the evening for low glycaemic index meal.
      No differences were observed in insulin responses. Despite the calculated
      difference in meal glycaemic index little difference was observed in morning
      responses, but differences were seen in the evening when insulin insensitivity is
      increasing, the glycaemic response increase was proportionally greater for low
      glycaemic index meals. CONCLUSIONS: Low glycaemic index foods are of less value
      in glycaemic control in the evening than the morning. Consuming food late in the
      day has a detrimental metabolic impact irrespective of glycaemic index.

PMID- 24135088
TI  - Translocation junctions in TCF3-PBX1 acute lymphoblastic leukemia/lymphoma
      cluster near transposable elements.
AB  - BACKGROUND: Hematolymphoid neoplasms frequently harbor recurrent genetic
      abnormalities. Some of the most well recognized lesions are chromosomal
      translocations, and many of these are known to play pivotal roles in
      pathogenesis. In lymphoid malignancies, some translocations result from erroneous
      V(D)J-type events. However, other translocation junctions appear randomly
      positioned and their underlying mechanisms are not understood. RESULTS: We tested
      the hypothesis that genomic repeats, including both simple tandem and
      interspersed repeats, are involved in chromosomal translocations arising in
      hematopoietic malignancies. Using a database of translocation junctions and
      RepeatMasker annotations of the reference genome assembly, we measured the
      proximity of translocation sites to their nearest repeat. We examined 1,174
      translocation breakpoints from 10 classifications of hematolymphoid neoplasms. We
      measured significance using Student's t-test, and we determined a false discovery
      rate using a random permutation statistics technique. CONCLUSIONS: Most
      translocations showed no propensity to involve genomic repeats. However,
      translocation junctions at the transcription factor 3 (TCF3)/E2A immunoglobulin
      enhancer binding factors E12/E47 (E2A) locus clustered within, or in proximity
      to, transposable element sequences. Nearly half of reported TCF3 translocations
      involve a MER20 DNA transposon. Based on this observation, we propose this
      sequence is important for the oncogenesis of TCF3-PBX1 acute lymphoblastic
      leukemia.

PMID- 24135089
TI  - Content validity of the Spanish version of the Practice Environment Scale of the
      Nursing Work Index.
AB  - OBJECTIVE: The objective of this study is to evaluate the content validity of the
      Iberian Spanish version of the questionnaire The Practice Environment Scale of
      the Nursing Work Index (PES-NWI) by using the Content Validity Indexing (CVI).
      METHODS: A descriptive cross-sectional observational study was conducted. The
      Spanish version of the questionnaire was translated from the American English
      instrument through forward and back translation processes. Experts evaluated the
      translated items through content validity indexing. Once the assessments were
      completed, CVI indicators were calculated: number of agreements, item Content
      Validity Index and overall content validity and modified kappa coefficient of the
      instrument. RESULTS: The overall content validity of the instrument was 0.82. The
      average modified kappa coefficient of the items was 0.80, with a rating of
      'excellent'. Only 4 of the items were rated as weak or poor. CONCLUSIONS: The
      study demonstrates that the content validity of the Spanish version of the PES
      NWI is acceptable. Some results indicate that some items have cross-cultural
      applicability challenges that need to be addressed in future research studies.
      Use of the instrument in other Spanish language speaking countries should be
      taken with caution since some words may not reflect the language of the
      healthcare systems there.

PMID- 24135090
TI  - Potential of zerovalent iron nanoparticles for remediation of environmental
      organic contaminants in water: a review.
AB  - Zerovalent iron (ZVI) has the potential to degrade different organic
      contaminants. Nanoscale zerovalent iron (NZVI) can reduce the contaminants even
      more rapidly due to its small size and large specific surface area (SSA),
      compared to granular ZVI. The main objective of this paper is to assess and
      compare the potential of NZVI for degradation of different contaminants in water
      under specific environmental conditions. As a first step, the potential reactive
      functional groups/bonds associated with different contaminants are identified and
      possible reaction mechanisms are discussed. Thereafter, the reaction efficiencies
      of different organic contaminants with NZVI are compared. Mass of ZVI and
      reaction time required to transform a certain amount of contaminated water are
      calculated based on literature data. Sources of contaminants in the environment
      and their environmental occurrences are discussed to understand the potential
      locations where NZVI could be applied for removal of different contaminants.
      Overall it is observed that azo-compounds are readily transformed in the presence
      of NZVI particles. Reaction efficiencies of ZVI for reduction of nitro-organic
      compounds are also reasonably high. However, halogenated compounds with high
      molecular weights or complex structures (i.e., iodinated contrast media, DDT,
      polychlorinated biphenyls, etc.) show lower reaction rates with NZVI compared to
      the widely studied chlorinated hydrocarbons (i.e., trichloroethylene). 

PMID- 24135091
TI  - A review of the detection, fate and effects of engineered nanomaterials in
      wastewater treatment plants.
AB  - Engineered nanomaterials (ENMs) are increasingly found in a wide range of
      products and processes, and consequently increasing loads are expected to reach
      wastewater treatment plants (WWTPs). To better assess the potential risk of ENMs
      to the environment via input through WWTP effluents, this review considers ENM
      detection methods, fate in WWTPs and potential effects on biota exposed to
      wastewater associated ENMs. Characterising ENMs in complex matrices presents many
      challenges, especially at low concentrations. Combining separation methods with
      techniques to assess particle size and chemical composition appears to be the
      most suitable approach for wastewater. In a range of studies, the majority of
      ENMs are removed from the aqueous phase by flocculation and sedimentation and
      remain in the sludge. However, ENM surface coating and the presence of organic
      matter and surfactants can alter removal. ENMs may affect biota via discharge of
      treated effluent to the aquatic environment or by application of sewage sludge to
      soil, although observed effects in laboratory studies only occurred at
      concentrations several orders of magnitude higher than the expected environmental
      levels. More realistic experimental designs with improved quantification of ENM
      properties under the selected test conditions are required to better understand
      the fate and effect of ENMs associated with WWTPs. 

PMID- 24135092
TI  - Monitoring and treatment of selected nanoparticles.
AB  - With their increasing use, nanoparticles will become concentrated in urban
      effluents in the future. Both adequate monitoring methods and water treatment
      technologies will be necessary to assess and avoid consumer exposure. This paper
      reports results in these two challenging areas for both organic and inorganic
      nanoparticles. Treatment experiments indicate that lamellar settling is better
      adapted than dissolved air flotation for SiO(2) nanoparticles removal. The use of
      120 mg/L of Aqualenc coagulant without flocculant addition allows 99% removal to
      be achieved for an initial concentration of 1 g/L. On the other hand, the
      dissolved air flotation process implemented under the usual industrial conditions
      does not permit removal of SiO(2) nanoparticles. In this case SiO(2) removal
      occurs only by settling in the flocculator tank. Application of a high resolution
      liquid chromatography/mass spectrometry (LC/MS) technique to a small selection of
      treated urban effluents indicates that C(60) fullerenes are not yet widely
      distributed in effluents; however non-point sources cannot be entirely ruled out.

PMID- 24135093
TI  - Effects of a saturated layer and recirculation on nitrogen treatment performances
      of a single stage Vertical Flow Constructed Wetland (VFCW).
AB  - Upgrades to enhance nitrogen removal were tested in a 2 year old pilot vertical
      flow constructed wetland in spring and summer periods. The effects of a saturated
      layer and of recirculation were tested in particular. Two pilots (L = 2 m, W =
      1.25 m, H = 1.2 m), filled with expanded schist (Mayennite((r))), were designed
      with hydraulic saturated layers of 20 and 40 cm at the bottom. Each pilot was fed
      with raw domestic wastewater under field conditions according to a hydraulic load
      of 15-38 cm d(-1) (i.e. 158-401 g COD (chemical oxygen demand) m(-2) d(-1)) and
      to recirculation rates ranging from 0% up to 150%. The initial load during the
      first 2 years of operation resulted in an incomplete mineralized accumulated
      sludge leading to total suspended solids (TSS), COD and biochemical oxygen demand
      (BOD5) release. A 40 cm hydraulic saturated layer enabled an increase of 5-10%
      total nitrogen (TN) removal compared to a 20 cm saturated layer. Recirculation
      allowed the dilution of raw wastewater and enhanced nitrification in a single
      stage. A design of 1.8 m2 pe(-1) (48 cm d(-1), 191 g COD m(-2) d(-1)) with a 40
      cm saturated layer and 100% recirculation enabled the French standard D4 (35 mg
      TSS L(-1), 125 mg COD L(-1), 25 mg BOD5 L(-1)), nitrogen concentrations below 20
      mg TKN (total Kjeldahl nitrogen) L(-1) and 50 mg TN L(-1), to be met. 

PMID- 24135094
TI  - Design and performance of hybrid constructed wetland systems for high-content
      wastewater treatment in the cold climate of Hokkaido, northern Japan.
AB  - The performance of six multistage hybrid constructed wetland systems was
      evaluated. The systems were designed to treat four kinds of high-content
      wastewater: dairy wastewater (three systems, average inflow content 2,400-5,000
      mg.COD l(-1), 3-6 years of operation); pig farm wastewater, including liquid food
      washing wastewater (one system, 9,500 mg.COD l(-1), 3 years); potato starch
      processing wastewater (one system, 20,000-60,000 mg.COD l(-1), 3 years); and
      wastewater containing pig farm swine urine (one system, 6,600 mg.COD l(-1), 2.8
      years) (COD = chemical oxygen demand). The systems contained three or four
      vertical (V) flow beds with self-priming siphons and surface partitions and no or
      one horizontal (H) flow bed (three to five beds). In some V flow beds, treated
      effluents were recirculated (Vr) through the inlet to improve performance. Mean
      annual temperature was 5-8  degrees C at all locations. To overcome clogging due
      to the high load in a cold climate, we applied a safety bypass structure and
      floating cover material to the V flow beds. Calculated average oxygen transfer
      rates (OTRs) increased proportionally with the influent load, and the OTR value
      was Vr > V> H. The relations of load-OTR, COD-ammonium, and a Arrhenius
      temperature-dependent equation enable the basic design of a reed bed system. 

PMID- 24135095
TI  - Experimental analysis of green roof substrate detention characteristics.
AB  - Green roofs may make an important contribution to urban stormwater management.
      Rainfall-runoff models are required to evaluate green roof responses to specific
      rainfall inputs. The roof's hydrological response is a function of its
      configuration, with the substrate - or growing media - providing both retention
      and detention of rainfall. The objective of the research described here is to
      quantify the detention effects due to green roof substrates, and to propose a
      suitable hydrological modelling approach. Laboratory results from experimental
      detention tests on green roof substrates are presented. It is shown that
      detention increases with substrate depth and as a result of increasing substrate
      organic content. Model structures based on reservoir routing are evaluated, and
      it is found that a one-parameter reservoir routing model coupled with a parameter
      that describes the delay to start of runoff best fits the observed data.
      Preliminary findings support the hypothesis that the reservoir routing parameter
      values can be defined from the substrate's physical characteristics. 

PMID- 24135096
TI  - The 21st Century Water Utility Initiative: how to boost operational performance
      of water utilities by up to 20%.
AB  - The 21st Century Water Utility Initiative is a powerful and innovative approach
      to help water utilities assess their current operational performance, identify
      improvement actions and track impact year after year. First success cases suggest
      that cost reductions range from 10 to 20% within 1-3 years, with improved
      customer satisfaction. This approach can help water utilities in three ways.
      First, its benchmarking module focusses on cost drivers at a granular level, not
      only at an asset level, but also by profit and loss line or activity. Second, it
      is coupled with onsite diagnostics to understand the causes of underperformance
      and identify improvement ideas. Third, its transformation programme makes
      operational changes stick through a combination of measures that address
      management infrastructure and mindsets and behaviour. In short, the Initiative
      helps utilities identify improvement potential, seize the prize, and translate it
      into a transformation programme to drive sustainable implementation. This highly
      structured, standardised approach addresses the needs of both small and large
      utilities. 

PMID- 24135097
TI  - Performance and behaviour of planted and unplanted units of a horizontal
      subsurface flow constructed wetland system treating municipal effluent from a
      UASB reactor.
AB  - A system composed of two horizontal subsurface flow constructed wetlands
      operating in parallel was evaluated for the post-treatment of UASB (upflow
      anaerobic sludge blanket) reactor effluent, for a population equivalent of 50
      inhabitants per unit. One unit was planted with cattail (Typha latifolia) and the
      other was unplanted. The study was undertaken over a period of 4 years,
      comprising monitoring of influent and effluent constituents together with a full
      characterization of the behaviour of the units (tracer studies, mathematical
      modelling of chemical oxygen demand (COD) decay, characterization of solids in
      the filter medium). The mean value of the surface hydraulic load was 0.11 m(3)m(
      2)d(-1), and the theoretical hydraulic retention time was 1.1 d in each unit.
      Using tracer tests with (82)Br, dispersion number (d) values of 0.084 and 0.079
      for the planted and unplanted units were obtained, indicating low to moderate
      dispersion. The final effluent had excellent quality in terms of organic matter
      and suspended solids, but the system showed low capacity for nitrogen removal.
      Four-year mean effluent concentration values from the planted and unplanted units
      were, respectively: biochemical oxygen demand (BOD(5)): 25 and 23 mg L(-1); COD:
      50 and 55 mg L(-1); total suspended solids (TSS): 9 and 9 mg L(-1); N-ammonia: 27
      and 28 mg L(-1). The COD decay coefficient K for the traditional plug-flow model
      was 0.81 and 0.84 d(-1) for the planted and unplanted units. Around 80% of the
      total solids present in the filter medium were inorganic, and most of them were
      present in the interstices rather than attached to the support medium. As an
      overall conclusion, horizontal subsurface flow wetlands can be a very suitable
      post-treatment method for municipal effluents from anaerobic reactors.

PMID- 24135098
TI  - Preparation of mesoporous activated carbon from palm-date pits: optimization
      study on removal of bentazon, carbofuran, and 2,4-D using response surface
      methodology.
AB  - Palm-date pits were used to prepare activated carbon by physiochemical activation
      method, which consisted of potassium hydroxide (KOH) treatment and carbon dioxide
      (CO(2)) gasification. The effects of variable parameters, activation temperature,
      activation time and chemical impregnation ratios (KOH: char by weight) on the
      preparation of activated carbon and for removal of pesticides: bentazon,
      carbofuran and 2,4-dichlorophenoxyacetic acid (2,4-D) were investigated. Based on
      the central composite design (CCD), two factor interaction (2FI) and quadratic
      models were respectively employed to correlate the effect of variable parameters
      on the preparation of activated carbon used for removal of pesticides with carbon
      yield. From the analysis of variance (ANOVA), the most influential factor on each
      experimental design response was identified. The optimum conditions for preparing
      activated carbon from palm-date pits were found to be: activation temperature of
      850  degrees C, activation time of 3 h and chemical impregnation ratio of 3.75,
      which resulted in an activated carbon yield of 19.5% and bentazon, carbofuran,
      and 2,4-D removal of 84, 83, and 93%, respectively.

PMID- 24135099
TI  - The effects of operating parameters on spiramycin removal by nanofiltration
      membrane.
AB  - Spiramycin removal from wastewater using four nanofiltration (NF) membranes
      (NF270, NF90, ESNA1-K1 and ESNA1-LF2-LD) was studied. The effects of operating
      pressure, feed temperature, feed concentration, cation and anion ions on the
      permeate flux rate and spiramycin rejection were investigated. The results show
      that increasing operating pressure resulted in the increase of both permeate flux
      and spiramycin rejection. The flux rate increased almost linearly with
      temperature, while the spiramycin rejection decreased. The permeate flux rate
      declined relatively with increasing feed concentration of spiramycin for NF270
      and ESNA1-LF2-LD membranes compared with NF90 and ESNA1-K membranes. The presence
      of cations reduced spiramycin rejection, with the strength of influence for the
      NF270 NF membrane following the order Mg(2+)>Ca(2+)>K(+). The presence of anions
      also resulted in decreased spiramycin rejection, the strength of the effect
      following the order NO(3)(-)>Cl(-)>SO(4)(2-) for the NF270 membrane.

PMID- 24135100
TI  - Short-term performance analysis of sludge treatment reed beds.
AB  - Sludge treatment reed beds (STRBs) represent an established technology for
      managing sludge produced by wastewater treatment plants (WWTPs). In this study,
      an analysis conducted on sludge stratigraphy in a STRB serving the municipal
      WWTPs of Helsinge (42,000 person equivalent, Denmark) is presented. The STRB has
      been in operation since 1996. The analysis was conducted for four months
      including two consecutive loadings of one of the 10 basins. The amount of
      dewatering during the short initial phase was significant, and the rehydration of
      deeper layers was negligible. A clear reduction trend was observed for volatile
      solids and labile organic matter, which is the first step towards organic matter
      humification. This hypothesis was also confirmed by water soluble carbon, which
      decreased with the increasing depth and the time of resting. About the N cycle,
      ammonification and nitrification showed a reciprocal balancing effect, so as to
      cause an equilibrium between the stable trends of NH(4)(+) and NO(3)(-) which
      were similar along the depth and the time of monitoring. The highest values of
      both parameters were found at the surface, where the combined effect of plant
      action, direct diffusive oxygen transfer from the atmosphere and high nutrient
      contents of the freshly loaded sludge was likely more intense.

PMID- 24135101
TI  - A novel and quick method to avoid H2O2 interference on COD measurement in Fenton
      system by Na2SO3 reduction and O2 oxidation.
AB  - Hydrogen peroxide interference on chemical oxygen demand (COD) measurement has
      been a big problem in the application of the Fenton process. However, there is no
      simple and effective method available to address this problem, although several
      methods have been reported in the literature. In this study, a new method has
      been developed based on Na(2)SO(3) reduction and O(2) oxidation, which has easy
      operation and short time requirement. Na(2)SO(3) reduction was used to remove
      H(2)O(2) in water samples, which was independent of pH in the investigated range
      of 2.50-11.95. Residual Na(2)SO(3) was removed by subsequent O(2) oxidation, and
      effects of initial solution pH, ferric ion dosage, and stirring speed were
      explored. Solution pH below 3.0 and stirring speed of 700 rev min(-1) could
      ensure a sufficiently high oxidation rate for Na(2)SO(3) with ferric ion higher
      than 0.469 mM. This new method was proven to be effective in the matrix of Fenton
      treating real landfill leachate. Meanwhile, the procedure for this method in
      other applications was proposed in detail. To the best of our knowledge, this
      newly developed method is the most simple and effective way to avoid H(2)O(2)
      interference on COD analysis.

PMID- 24135102
TI  - Pulsed corona discharge: the role of ozone and hydroxyl radical in aqueous
      pollutants oxidation.
AB  - Ozone and hydroxyl radical are the most active oxidizing species in water treated
      with gas-phase pulsed corona discharge (PCD). The ratio of the species dependent
      on the gas phase composition and treated water contact surface was the objective
      for the experimental research undertaken for aqueous phenol (fast reaction) and
      oxalic acid (slow reaction) solutions. The experiments were carried out in the
      reactor, where aqueous solutions showered between electrodes were treated with
      100-ns pulses of 20 kV voltage and 400 A current amplitude. The role of ozone
      increased with increasing oxygen concentration and the oxidation reaction rate.
      The PCD treatment showed energy efficiency surpassing that of conventional
      ozonation. 

PMID- 24135103
TI  - Sorption of heavy metals in the biomass of alga Palmaria palmata.
AB  - Sorption of heavy metals by the sea alga Palmaria palmata was investigated in
      laboratory conditions. The sorption process of the analytes was carried out with
      constant flow of the solutions through the algae samples. The Langmuir isotherm
      model was used to describe equilibria. The experiments confirmed that 50 min of
      exposure of algae with little heavy metal contamination in contaminated waters
      results in the increase of concentration of these analytes, proportional to their
      concentration in the tested waters. On the basis of the Langmuir isotherm
      direction factor, a = (c(a,max) * K)(-1), affinity of heavy metals and algae
      increases in the following sequence: Mn(2+) < Zn(2+) ~ Cd(2+) < Cu(2+), and the
      competitiveness of sorption of cations naturally present in the algae environment
      versus Zn(2+) ions changes according to following sequence: Na(+) < Ca(2+) <
      H(+), defined for the concentrations referring to the ion unit charge. It was
      also confirmed, that the presence of sodium and calcium ions in the solutions,
      within the conductivity range from 200 to 1,000 MUS/cm, is not statistically
      significant for the sorption of heavy metals from these solutions. 

PMID- 24135104
TI  - Sorption of lead ions from aqueous solution onto Enterococcus faecium biomass.
AB  - This study reports kinetics and equilibrium of lead sorption onto the biomass of
      Enterococcus faecium. E. faecium is a lactic acid bacterium and was isolated from
      meat. Batch experiments were carried out to analyze the effects of the initial
      lead concentration, initial pH of the medium, agitation time and temperature on
      the biosorption. The lead sorption was found to increase with the increase in the
      solution pH, reaching a plateau value beyond pH 5, and the most favorable pH for
      removal was determined as 5.0. The highest lead uptake capacity of the biomass
      was obtained at the initial lead concentration of 300 mg L(-1). The Langmuir and
      Freundlich adsorption models were applied to determine the biosorption isotherm,
      and the equilibrium data correlated well with the Langmuir model. The pseudo
      second-order kinetic model was more suitable to fit the experimental data. The
      results were promising that the biomass of this lactic acid bacterium can be
      successfully used as a convenient adsorbent for lead removal from aqueous
      solutions. 

PMID- 24135105
TI  - Characterization of bacterial isolates from water reclamation systems on the
      basis of substrate utilization patterns and regrowth potential in reclaimed
      water.
AB  - Microbial regrowth causes problems during water reuse. Comprehensive
      understanding of the microorganisms that can regrow in reclaimed water and their
      substrate requirements are necessary. In this study, potential regrowth organisms
      were isolated from seven water reclamation plants in Japan. Based on 16S rDNA
      analysis, the isolates were grouped into 34 operational taxonomic units,
      belonging to Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria,
      Actinobacteria, Bacteroidetes, and Firmicutes. Substrate utilization profiling
      using Biolog microplateTM classified the isolates into four groups. Bacteria in
      Cluster 1 (e.g., Methylobacterium sp. and Acinetobacter sp.) mainly utilized
      polymers, esters, amides, and alcohol. Isolates in Cluster 2 (e.g.,
      Flavobacterium sp. and Microbacterium sp.) preferred to utilize polymers,
      carbohydrates, and esters. Isolates in Cluster 3 (e.g., Pseudomonas sp. and
      Acidovorax sp.) mainly utilized esters, carboxylic acids, and amino acids.
      Isolates in Cluster 4 (e.g., Enterobacter sp. and Rhodococcus sp.) utilized
      carbohydrates, esters, and amino acids. All isolates grew in reclaimed water
      treated by sand filtration, whereas some isolates could not grow in reclaimed
      water treated by coagulation and ozonation. Most bacteria in the same Biolog
      clusters exhibited similar growth characteristics in water samples. The potential
      of bacteria to regrow in reclaimed water likely depended on substrate
      requirement. 

PMID- 24135106
TI  - Treatment of wastewater and restoration of aquatic systems through an eco
      technology based constructed treatment wetlands - a successful experience in
      Central India.
AB  - In the last couple of decades constructed wetlands (CWs) have drawn considerable
      interest in Central India. CWs offer an effective means of integrating wastewater
      treatment and resource enhancement, often at competitive cost in comparison to
      conventional wastewater treatments, with additional benefits of Green Urban
      Landscaping and wildlife habitat. This paper describes treatment performances and
      the design of some Sub Surface Flow CWs (SSFCW) and Artificial Floating Islands
      (AFIs) in Central India. Central Indian CWs show significant pollution reduction
      load for total suspended solids (TSS) (62-82%), biochemical oxygen demand (BOD)
      (40-75%), NH(4)-N (67-78%) and total Kjeldahl nitrogen (TKN) (59-78%). Field
      scale SSFCWs installed so far in Central India are rectangular, earthen,
      single/multiple celled having similar depths of 0.60-0.90 m, hydraulic retention
      capacity 18-221 m(3) with effective size 41.8-1,050 m(2). The major components of
      CWs incorporate puddled bottom/side walls, sealed with impermeable low-density
      polyethylene, a bed of locally available river gravel planted with Phragmites
      karka, and an inlet distribution and outlet collection system. A new variant on
      CWs are AFIs working under hydroponics. The field scale experimental AFIs
      installed in-situ in a slowly flowing local river were composed of hollow bamboo,
      a bed of coconut coir, floating arrangements and Phragmites karka as nutrient
      stripping plant species. The AFIs polish the aquatic system by reducing 46.6% of
      TSS, 45-55% of NH(4)-N, 33-45% of NO(3)-N, 45-50% of TKN and 40-50% of BOD. The
      study established that there is a need for further research and sufficient data
      to assist the development of CWs by instilling confidence in policymakers,
      planners and in the public.

PMID- 24135107
TI  - Optimization of a hydrodynamic separator using a multiscale computational fluid
      dynamics approach.
AB  - This article deals with the optimization of a hydrodynamic separator working on
      the tangential separation mechanism along a screen. The aim of this study is to
      optimize the shape of the device to avoid clogging. A multiscale approach is
      used. This methodology combines measurements and computational fluid dynamics
      (CFD). A local model enables us to observe the different phenomena occurring at
      the orifice scale, which shows the potential of expanded metal screens. A global
      model is used to simulate the flow within the device using a conceptual model of
      the screen (porous wall). After validation against the experimental measurements,
      the global model was used to investigate the influence of deflectors and disk
      plates in the structure. 

PMID- 24135108
TI  - Organics removal and protein recovery from wastewater discharged during the
      production of chondroitin sulfate.
AB  - Bentonite, chitosan and polyaluminum chloride (PAC) were applied to treat
      wastewater discharged during the production of chondroitin sulfate and recover
      protein dissolved in the wastewater. The results showed that the combination of
      pH 9.00, 3-4 mL chitosan solution, 2 g of bentonite and 5 mL of 8% PAC solution
      per 100 mL of wastewater with a 4.0 h flocculation time were the optimal
      conditions for the recovery of protein and removal of total organic carbon (TOC)
      from wastewater. A pilot-scale test also was conducted, and 130 kg (dry weight)
      of sediment was obtained from 1.1 m(3) of discharged wastewater. This sediment
      contained abundant amino acids (proteins comprised 61% of the total sediment),
      after the recovery of protein, the dissolved TOC concentration in wastewater was
      decreased by approximately 80% and the residual wastewater could be readily
      disposed using a traditional activated sludge process. 

PMID- 24135109
TI  - Improved methane production from waste activated sludge with low organic content
      by alkaline pretreatment at pH 10.
AB  - Sludge with low organic content always results in an unsatisfactory performance,
      even failure of anaerobic digestion. The alkaline pretreatment effect on
      anaerobic digestion of sludge with low organic content has seldom been studied
      although it gives many benefits for sludge with high organic content. In this
      study the influence of alkaline pretreatment (pH 10, an effective alkaline pH) on
      the solubilization and methane production from waste activated sludge (WAS) with
      low organic content was investigated. Results from biochemical methane potential
      (BMP) experiments showed that anaerobic biodegradability of WAS was greatly
      improved by alkaline pretreatment at pH 10. Methane production from the current
      WAS under conditions of pretreatment time 4 h and digestion time 15 d was 139.6
      mL/g VS (volatile solids), much higher than that from the unpretreated WAS with
      digestion time of 20 d (75.2 mL/g VS). Also, the solubilization of WAS was
      significantly accelerated by alkaline pretreatment. Mechanism exploration
      indicated that the general activities of anaerobic microorganisms, specific
      activities of key enzymes and the amounts of methanogens were enhanced by
      alkaline pretreatment at pH 10, showing good agreement with methane production. 

PMID- 24135110
TI  - Performance of a single stage vertical flow constructed wetland system treating
      raw domestic sewage in Brazil.
AB  - This study investigated the behaviour of two intermittently fed vertical flow
      constructed wetlands (one planted with Tifton 85 and the other unplanted) working
      in parallel, treating raw municipal sewage in Brazil for a population equivalent
      around 100 inhabitants. Based on a monitoring programme of over 2 years, the
      following items were evaluated: influence of batch frequency and the presence of
      Tifton 85 on the wetlands performance in terms of several physico-chemical and
      biological constituents. The unit with plants performed better than the one
      without, indicating a positive influence of the presence of plants. More
      attachment by total and volatile solids and larger amount of bacteria involved in
      the nitrogen cycle were observed in the planted filter medium, which can explain
      its higher nitrification and solids removal. The application of a smaller
      influent volume with a higher batch frequency improved the performance of both
      units. No signs of medium clogging have been observed in both units. The system
      simplicity and the good removal efficiency of organic matter, suspended solids,
      ammonia and helminth eggs indicate its high applicability in small communities in
      developing countries such as Brazil. 

PMID- 24135111
TI  - Experimental design for the evaluation of struvite sedimentation obtained from an
      ammonium concentrated wastewater.
AB  - Chemical precipitation of struvite as a technique of ammonium nitrogen (NH(4)-N)
      removal from concentrated wastewater has been shown to be an attractive
      alternative due to its high effectiveness, reaction rate, simplicity,
      environmental sustainability and, especially, the application potential of the
      generated solids for the fertilizer industry. The technique of experimental
      design has been used in order to identify and evaluate the optimum conditions of
      chemical precipitation reaction applied in a struvite sedimentation study. The
      preliminary tests were performed using synthetic effluent with a concentration
      equal to 500.0 mg N L(-1). The stoichiometric ratio Mg:NH(4):PO(4) equal to
      1.5:1.0:1.25 and pH equal to 8.5 were taken to be the optimum conditions, where a
      NH(4)-N removal equal to 98.6% was achieved with only 10-min reaction time. This
      condition has been used to evaluate the struvite sedimentation from synthetic
      wastewaters, intending to check the optimum conditions achieved by the
      experimental design in different initial concentrations, 1,000 and 2,000 mg N L(
      1). The results were typical of a good zonal sedimentation and can be used in the
      scale up the system.

PMID- 24135112
TI  - Synthesized heterogeneous Fenton-like goethite (FeOOH) catalyst for degradation
      of p-chloronitrobenzene.
AB  - The removal of p-chloronitrobenzene (pCNB) was investigated by a heterogeneous
      Fenton-like system using a laboratory synthesized goethite (FeOOH) as catalyst.
      The influencing factors and the degradation pathway of pCNB were also evaluated.
      With a stronger catalytic activity than Fe(2+) catalyst, the synthesized FeOOH
      catalyst can significantly promote the decomposition of H(2)O(2), and the
      decomposition product hydroxyl radicals (.OH) can oxidize pCNB in the water
      effectively. The FeOOH catalyst can also adsorb a certain amount of pCNB, and the
      adsorption effect is related to the amount of FeOOH and the initial pH value of
      solution. The results of liquid chromatography-mass spectrometry (LC-MS) and gas
      chromatography-mass spectrometry (GC-MS) showed that the main intermediate
      products were phenolic compounds and carbonyl compounds. About 60% of pCNB was
      mineralized during the catalytic oxidation, and chlorine and nitro groups on
      benzene ring were converted into Cl(-) and NO(3)(-) after being attacked.

PMID- 24135113
TI  - Influence of conditioning agents and enzymic hydrolysis on the biochemical
      methane potential of sewage sludge.
AB  - Biochemical methane potential (BMP) tests have been carried out on sewage sludge
      from two wastewater treatment plants to assess the effect of additives (FeCl(3)
      and two cationic polyelectrolytes) used in sludge dewatering. BMP tests were also
      carried out on the concentrated solid phase from the enzymic hydrolysis pre
      treatment (42  degrees C, 48 h). FeCl(3) had no significant effect on specific
      methane production, obtaining 242-246 LCH(4)/kgVSo. The effect of the combination
      of polyelectrolyte and FeCl(3) depended on the polyelectrolyte and the sludge,
      but generally led to an increase in specific methane production (25-40%). When
      enzymic hydrolysis was applied as a pre-treatment, specific methane production
      increased from 6.8% in the sludge containing FeCl(3) to 20% in the sludge without
      FeCl(3), although the increases were not statistically significant. In terms of
      LCH(4)/kgVS(rem), a general improvement was achieved both by means of additives
      and by enzymic hydrolysis. However, this improvement was only significant in the
      case of sludge which had undergone previous enzymic hydrolysis (62%) and in the
      untreated sludge containing a polyelectrolyte and FeCl(3) (24%). Cationic
      polyelectrolytes inhibited solid-liquid separation during enzymic hydrolysis and,
      although the presence of only FeCl(3) did not affect this separation, a
      significant decrease (32%) in LCH(4)/kgVSrem was observed.

PMID- 24135114
TI  - An EGSB-SBR based process for coupling methanogenesis and shortcut nitrogen
      removal.
AB  - An integrated process consisting of an anaerobic/anoxic expanded granular sludge
      bed (EGSB) reactor and an aerobic sequencing batch reactor (SBR) was developed by
      a mode of sequencing batch operation, in which methanogenesis, denitrification
      and anammox were coupled in EGSB with methanogenesis first, then denitrification
      and anammox simultaneously, and partial nitrification occurred in SBR for
      providing nitrite to EGSB. This process extended the application of the anammox
      process to the treatment of wastewater containing high concentrations of chemical
      oxygen demand (COD) and ammonium. When the volumetric exchange ratio between EGSB
      and SBR was controlled at 57% with the influent pH at 6-8, 74.38-83.65% of
      NH(4)(+)-N, 72.68-83.12% of total nitrogen (TN) and 88.34-98.86% of COD were
      removed in a range of 200-4,500 mg/L COD and 40-90 mg/L NH(4)(+)-N respectively.
      TN removal by anammox and shortcut denitrification was 26.35-58.64 and 0-32.80%
      of the removed nitrogen, respectively. The results showed that the contribution
      of anammox gradually decreased with an increase in the C/N ratio of influent,
      whereas the reverse was true for shortcut denitrification. The COD removal by
      methanogenesis was 70.89-98.79% of the removed COD, and increased with increasing
      C/N ratio.

PMID- 24135115
TI  - Empirical regression models for estimating nitrogen removal in a stormwater
      wetland during dry and wet days.
AB  - Due to the highly variable hydrologic quantity and quality of stormwater runoff,
      which requires more complex models for proper prediction of treatment, a
      relatively few and site-specific models for stormwater wetlands have been
      developed. In this study, regression models based on extensive operational data
      and wastewater wetlands were adapted to a stormwater wetland receiving both base
      flow and storm flow from an agricultural area. The models were calibrated in
      Excel Solver using 15 sets of operational data gathered from random sampling
      during dry days. The calibrated models were then applied to 20 sets of event mean
      concentration data from composite sampling during 20 independent rainfall events.
      For dry days, the models estimated effluent concentrations of nitrogen species
      that were close to the measured values. However, overestimations during wet days
      were made for NH(3)-N and total Kjeldahl nitrogen, which resulted from higher
      hydraulic loading rates and influent nitrogen concentrations during storm flows.
      The results showed that biological nitrification and denitrification was the
      major nitrogen removal mechanism during dry days. Meanwhile, during wet days, the
      prevailing aerobic conditions decreased the denitrification capacity of the
      wetland, and sedimentation of particulate organic nitrogen and particle
      associated forms of nitrogen was increased.

PMID- 24135116
TI  - Relationship between water quality parameters and the survival of indicator
      microorganisms - Escherichia coli - in a stormwater wetland.
AB  - Indicator microorganisms - Escherichia coli - in a stormwater wetland controlling
      non-point source pollution in the Keum River basin was studied and the
      relationship between water quality parameters and the survival of E. coli was
      investigated by Pearson correlation analysis based on 16 sets of data collected
      on dry days. A significant seasonal variation of the density of E. coli was
      observed in the influent and effluent. A dominant decay of E. coli was found in
      almost all the wetland components. In the settling pond, the density was observed
      to vary negatively with pH and the removal of total suspended solids, and the
      decay was promoted by solar radiation. In the aeration pond, the survival of E.
      coli was encouraged negatively by the dilution effect, unfavorable increase of
      dissolved oxygen (DO) and sedimentation with coarse particles. In the marsh
      wetland, the reduction of E. coli was positively influenced by UV radiation,
      obvious increase of pH, DO and sedimentation with algae and particles. In the
      polishing pond, the introduction of E. coli with avian feces and growth of the
      bacteria were more prevalent than decay. Although this introduction or growth was
      almost negligible, further study will be conducted in the future. 

PMID- 24135117
TI  - Stormwater nitrogen removal performance of a floating treatment wetland.
AB  - The nitrogen (N) removal efficiency and effluent quality of two parallel
      stormwater retention ponds, one retrofitted with a floating treatment wetland
      (FTW) and one without any vegetation, was compared in a field trial. This study
      shows that inclusion of FTWs in stormwater retention ponds has potential to
      moderately improve N removal. Median FTW outlet event mean concentrations (EMCs)
      were lower than median inlet and control pond outlet EMCs for all species of N,
      except for NH(4)-N. Performance was statistically better from late spring to end
      autumn due to higher organic nitrogen (ON) removal and denitrification in
      presence of the FTW. Low dissolved oxygen (DO), higher temperature and increased
      organic matter (OM) and microbial activity below the FTW, likely facilitated the
      higher denitrification rates observed over this period. Greater sediment N
      accumulation in the FTW pond also contributed to its higher overall N removal.
      Higher OM availability in the FTW pond due to release of root exudates and supply
      of detritus from plant die-back may have contributed to floc formation in the
      water column, increasing particulate ON settlement. Enhanced ON mineralisation
      may also be responsible but was probably limited in summer due to the low DO
      induced by the FTW. Direct uptake by the plants appears to be of less importance.

PMID- 24135118
TI  - Tertiary treatment of Berlin WWTP effluents with ferrate (Fe(VI)).
AB  - New and higher standards in the EU water framework directive necessitate advanced
      treatment of secondary effluents for reduction of trace organic compounds (TrOCs)
      and nutrients before the discharge into receiving surface waters. Due to its dual
      function as oxidant and coagulant, ferrate is considered as a promising
      alternative for tertiary treatment. The oxidation of selected TrOCs and
      simultaneous flocculation of phosphates by ferrate was tested in batch
      experiments with secondary effluent from Berlin Ruhleben. The concentrations of
      carbamazepine (CBZ) and diclofenac were reduced by >90% with ferrate dosages of 6
      mg/L as Fe. CBZ was transformed to 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline
      2-one, which is known as the major product from the reaction of CBZ with ozone.
      In contrast to ozonation, no further transformation of this product was observed.
      The concentration of ibuprofen was not reduced by ferrate treatment. For
      efficient removal of 60-100 MUg/L phosphate-P to values <20 MUg/L, ferrate
      dosages of 3-4 mg/L as Fe were sufficient. 

PMID- 24135119
TI  - Constructed wetlands as an alternative restoration measure for shallow lakes.
AB  - This paper deals with the consequences of cultural eutrophication and
      unconventional solutions for shallow lake restoration. Cultural eutrophication is
      the primary problem that affects especially shallow lakes, due to their physical
      characteristics (e.g. shallow depth, lack of stratification). Palic Lake, a very
      shallow Pannonian lake, received treated municipal wastewaters coming from the
      lagoons of a wastewater treatment plant. The sewage discharge mainly increased
      the nutrient load to the lake in the last decades. The lake sustainability is
      affected by inappropriate quality of water that flows into the lake, and
      abundance of deposited sediment. The technology that can provide both improvement
      of water quality and resolution of the sediment problem is a constructed wetland,
      which is designed to utilise the natural processes involving wetland vegetation,
      soil and their associated microbial assemblages to assist in additional water
      treatment. The technical solution is based on three key aspects: quality and
      quantity of deposited sediment, enriched by nutrients; effluent quality; desired
      lake water quality. A designed constructed wetland can accomplish the desired
      water quality and gradually remediate deposited sediment. 

PMID- 24135120
TI  - Uterine rupture in twin pregnancy with normal fetus and complete hydatidiform
      mole.
AB  - We describe a rare case of complete hydatidiform mole with twin live fetus
      (CHMTF) confirmed by histopathology, flow cytometry and polymerase chain reaction
      techniques. No malformations were observed, fetal karyotype was normal and beta
      human chorionic gonadotropin levels were high (>100,000 IU/ml). The patient was
      informed of the risks and decided to continue with the pregnancy, but at week 15,
      she had to undergo hysterectomy due to uterine rupture. She subsequently
      developed persistent trophoblastic disease (PTD) with pulmonary metastases that
      required treatment with polychemotherapy. Patients with CHMTF should be informed
      of all known risks, including the considerable risk of PTD, which is similar to
      or, even higher than that associated with a singleton complete mole. The risk
      does not appear to be increased by continuing the pregnancy. Because so few
      series have been published, there is a lack of evidence-based clinical management
      guidelines. To our knowledge, this is the first report of uterine rupture in
      CHMTF.

PMID- 24135121
TI  - 3-D analysis of dictyosomes and multivesicular bodies in the green alga
      Micrasterias denticulata by FIB/SEM tomography.
AB  - In the present study we employ FIB/SEM tomography for analyzing 3-D architecture
      of dictyosomes and formation of multivesicular bodies (MVB) in high pressure
      frozen and cryo-substituted interphase cells of the green algal model system
      Micrasterias denticulata. The ability of FIB/SEM of milling very thin 'slices' (5
      10 nm), viewing the block face and of capturing cytoplasmic volumes of several
      hundred MUm(3) provides new insight into the close spatial connection of the ER
      Golgi machinery in an algal cell particularly in z-direction, complementary to
      informations obtained by TEM serial sectioning or electron tomography. Our
      FIB/SEM series and 3-D reconstructions show that interphase dictyosomes of
      Micrasterias are not only closely associated to an ER system at their cis-side
      which is common in various plant cells, but are surrounded by a huge "trans-ER"
      sheath leading to an almost complete enwrapping of dictyosomes by the ER. This is
      particularly interesting as the presence of a trans-dictyosomal ER system is well
      known from mammalian secretory cells but not from cells of higher plants to which
      the alga Micrasterias is closely related. In contrast to findings in plant
      storage tissue indicating that MVBs originate from the trans-Golgi network or its
      derivatives our investigations show that MVBs in Micrasterias are in direct
      spatial contact with both, trans-Golgi cisternae and the trans-ER sheath which
      provides evidence that both endomembrane compartments are involved in their
      formation.

PMID- 24135122
TI  - A multicenter controlled trial on knowledge and attitude about cardiopulmonary
      resuscitation among secondary school children in Malaysia.
AB  - BACKGROUND: We performed a multicenter controlled trial to assess the knowledge
      and attitude (KA) about cardiopulmonary resuscitation (CPR) among secondary
      school children in a district in Malaysia. METHODS: This was a prospective
      intervention study. The primary endpoint of the study was to determine the level
      of KA about resuscitation after CPR training. The six schools and classes from
      selected schools were chosen by randomization among the form three and four
      classes using sealed envelopes. A fully validated questionnaire consisting of
      three sections (sociodemographic, knowledge and attitude) was given to the pupils
      before and 2 weeks after the intervention. The intervention group was given a
      lecture, video show, pamphlet and 1-h practical session on CPR training. The
      control group received a placebo in order to overcome the learning effect. The
      maximum scores for the knowledge and attitude sections were 72 and 28,
      respectively. Repeated measures ANOVA analysis was used for specific objectives
      to determine the changes in knowledge and attitude level pre- and post
      intervention for both study groups. P-values less than 0.05 were taken as
      significant at 95% confidence intervals. RESULTS: The mean (SD) total knowledge
      scores for the intervention (n = 216) and control (n = 252) groups were 62.43
      (13.68) and 62.29 (12.11), respectively (maximum score 72) (p > 0.05). On the
      other hand, the mean (SD) total attitude scores for the intervention and the
      control groups were 19.33 (4.51) and 17.85 (4.52), respectively (maximum score
      28) (p < 0.001). There were significant differences in mean knowledge and
      attitude scores between the intervention and control groups with regard to time
      (pre- and post-intervention). The mean difference in knowledge and attitude
      scores between both study groups was 8.31 (p < 0.001) and 2.39 (p < 0.001),
      respectively. CONCLUSIONS: The level of knowledge and attitudes of secondary
      school children was shown to be acceptable prior to the intervention.
      Furthermore, a brief CPR training program improved their level of knowledge and
      attitudes significantly as compared to those who had never been trained.

PMID- 24135123
TI  - Hajj pilgrims knowledge about Middle East respiratory syndrome coronavirus,
      August to September 2013.
AB  - In preparation for Hajj 2013, 360 French pilgrims were interviewed regarding
      their knowledge about Middle East respiratory syndrome (MERS). Respondents were
      aged 20-85 years, male-female ratio was 1.05:1;64.7% were aware of the MERS
      situation in Saudi Arabia; 35.3% knew about the Saudi Ministry of Health
      recommendations for at-risk pilgrims to postpone participation in the 2013 Hajj.
      None of 179 at-risk individuals(49.9%) decided to cancel their Hajj participation
      even after advice during consultation.

PMID- 24135124
TI  - Late season interim estimates of influenza vaccine effectiveness reliably predict
      end of season estimates in Victoria, Australia, 2007 to 2012.
AB  - Twice each year the World Health Organization makes a recommendation for the
      composition of the influenza vaccine, based on circulating strains of influenza
      A(H3N2), A(H1N1) and B. Strain selection has always been based on immunogenicity
      studies with limited human data. Immunogenicity can be considered as a proxy for
      vaccine effectiveness (VE). However, only interim VE estimates for the target
      hemisphere can be considered in time for the strain selection meeting.Using
      surveillance data from Victoria, Australia, we retrospectively estimated and
      compared interim and final VE estimates for 2007 to 2012. In general, interim
      estimates were within five percentage points of final estimates. However,
      estimates made too early or in years of low influenza activity may be unreliable.

PMID- 24135125
TI  - A dynamic case definition is warranted for adequate notification in an extended
      epidemic setting: the Dutch Q fever outbreak 2007-2009 as exemplar.
AB  - Q fever is a notifiable disease in the Netherlands:laboratories are obliged to
      notify possible cases to the Municipal Health Services. These services then try
      to reconfirm cases with additional clinical and epidemiological data and provide
      anonymised reports to the national case register of notifiable diseases. Since
      the start of the 2007-2009 Dutch Q fever outbreak,notification rules remained
      unchanged, despite new laboratory insights and altered epidemiology. In this
      study, we retrospectively analysed how these changes influenced the proportion of
      laboratory-defined acute Q fever cases (confirmed, probable and possible)that
      were included in the national case register, during(2009) and after the outbreak
      (2010 and 2011).The number of laboratory-defined cases notified to the Municipal
      Health Services was 377 in 2009, 96 in 2010 and 50 in 2011. Of these, 186 (49.3%)
      in 2009, 12(12.5%) in 2010 and 9 (18.0%) in 2011 were confirmed as acute
      infection by laboratory interpretation. The proportion of laboratory-defined
      acute Q fever cases that was reconfirmed by the Municipal Health Services and
      that were included in the national case register decreased from 90% in 2009, to
      22% and 24% in 2010 and 2011, respectively. The decrease was observed in all
      categories of cases, including those considered to be confirmed by laboratory
      criteria. Continued use ofa pre-outbreak case definition led to over-reporting of
      cases to the Municipal Health Services in the post-epidemic years. Therefore we
      recommend dynamic laboratory notification rules, by reviewing case definitions
      periodically in an ongoing epidemic, as in the Dutch Q fever outbreak.

PMID- 24135128
TI  - Thermal cycling for restorative materials: does a standardized protocol exist in
      laboratory testing? A literature review.
AB  - In vitro tests continue to be an indispensable method for the initial screening
      of dental materials. Thermal cycling is one of the most widely used procedures to
      simulate the physiological aging experienced by biomaterials in clinical
      practice. Consequently it is routinely employed in experimental studies to
      evaluate materials' performance. A literature review aimed to elucidate test
      parameters for in vitro aging of adhesive restorations was performed. This study
      aims to assess whether or not a standardized protocol of thermal cycling has been
      acknowledged from a review of the literature. An exhaustive literature search,
      examining the effect of thermal cycling on restorative dental materials, was
      performed with electronic database and by hand. The search was restricted to
      studies published from 1998 to August 2013. No language restrictions were
      applied. The search identified 193 relevant experimental studies. Only twenty
      three studies had faithfully applied ISO standard. The majority of studies used
      their own procedures, showing only a certain consistency within the temperature
      parameter (5-55 degrees C) and a great variability in the number of cycles and
      dwell time chosen. A wide variation in thermal cycling parameters applied in
      experimental studies has been identified. The parameters selected amongst these
      studies seem to be done on the basis of convenience for the authors in most
      cases. A comparison of results between studies would appear to be impossible. The
      available data suggest that further investigations will be required to ultimately
      develop a standardized thermal cycling protocol. 

PMID- 24135129
TI  - Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced
      dyskinesia.
AB  - The serotonin system has emerged as a potential target for anti-dyskinetic
      therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA
      into dopamine, and mediate its synaptic release. However, they lack a feedback
      control mechanism able to regulate synaptic dopamine levels, which leads to un
      physiological stimulation of post-synaptic striatal dopamine receptors.
      Accordingly, drugs able to dampen the activity of serotonin neurons can suppress
      L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we
      investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to
      counteract L-DOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and
      MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced
      dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques
      was accompanied by a worsening of the Parkinson's disease score at significantly
      effective doses (1.5 and 2.0mg/kg). At a lower dose (0.75mg/kg), anpirtoline
      markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance
      was prevented by the presence of a non-responsive subject. These results provide
      further evidence that the serotonin neurons contribute both to the pro-dyskinetic
      effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of
      Parkinson's disease. 

PMID- 24135130
TI  - Corticospinal neuroprostheses to restore locomotion after spinal cord injury.
AB  - In this conceptual review, we highlight our strategy for, and progress in the
      development of corticospinal neuroprostheses for restoring locomotor functions
      and promoting neural repair after thoracic spinal cord injury in experimental
      animal models. We specifically focus on recent developments in recording and
      stimulating neural interfaces, decoding algorithms, extraction of real-time
      feedback information, and closed-loop control systems. Each of these complex
      neurotechnologies plays a significant role for the design of corticospinal
      neuroprostheses. Even more challenging is the coordinated integration of such
      multifaceted technologies into effective and practical neuroprosthetic systems to
      improve movement execution, and augment neural plasticity after injury. In this
      review we address our progress in rodent animal models to explore the viability
      of a technology-intensive strategy for recovery and repair of the damaged nervous
      system. The technical, practical, and regulatory hurdles that lie ahead along the
      path toward clinical applications are enormous - and their resolution is
      uncertain at this stage. However, it is imperative that the discoveries and
      technological developments being made across the field of neuroprosthetics do not
      stay in the lab, but instead reach clinical fruition at the fastest pace
      possible. 

PMID- 24135131
TI  - An Internet-based intervention for eating disorders consisting of automated
      computer-tailored feedback with or without supplemented frequent or infrequent
      support from a coach: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Several Internet-based interventions for eating disorders have shown
      their effectiveness. Still, there is a need to refine such interventions given
      that most existing programs seem to be limited by their static 'one-size-fits
      all' approach. 'Featback', an Internet-based intervention for symptoms of eating
      disorders provides a more individualized approach. It consists of several
      components (psychoeducation, a fully automated monitoring and feedback system,
      and support from a coach), which can be matched to participants' needs and
      preferences. Until now, it is unclear whether online self-help interventions for
      eating disorders with support are more effective than those without. The aims of
      the current study are i) to examine the relative effectiveness of (the different
      components of) Featback; ii) to examine predictors, moderators and mediators of
      intervention responses; iii) to report on practical experiences with Featback;
      and iv) to examine the cost-effectiveness of Featback. METHODS/DESIGN:
      Individuals aged 16 years or older, with mild to severe eating disorder symptoms
      will be randomized to one of the four study conditions. In condition one,
      participants receive the basic version of Featback, consisting of psychoeducation
      and a fully automated monitoring and feedback system. In conditions two and
      three, participants receive the basic version of Featback supplemented with the
      possibility of infrequent (weekly) or frequent (three times a week) e-mail, chat,
      or Skype support from a coach, respectively. The fourth condition is a waiting
      list control condition. Participants are assessed at baseline, post-intervention
      (8 weeks), and at 3- and 6-month follow-up (the latter except for participants in
      the waiting list control condition). Primary outcome measures are disordered
      eating behaviors and attitudes. Secondary outcome measures are (eating disorder
      related) quality of life, self-stigma of seeking help, self-esteem, mastery and
      support, symptoms of depression and anxiety, repetitive negative thinking,
      motivation to change, user satisfaction, compliance, and help-seeking attitudes
      and behaviors. DISCUSSION: This study aims to provide more insight into the (cost
      ) effectiveness of Internet-based interventions for eating disorders,
      particularly those with and without professional support, as well as different
      levels of support. TRIAL REGISTRATION: NTR3646.

PMID- 24135133
TI  - The representation of category typicality in the frontal cortex and its cross
      linguistic variations.
AB  - When asked to judge the membership of typical (e.g., car) vs. atypical (e.g.,
      train) pictures of a category (e.g., vehicle), native English (N=18) and native
      Chinese speakers (N=18) showed distinctive patterns of brain activity despite
      showing similar behavioral responses. Moreover, these differences were mainly due
      to the amount and pervasiveness of category information linguistically embedded
      in the everyday names of the items in the respective languages, with important
      differences across languages in how pervasive category labels are embedded in
      item-level terms. Nonetheless, the left inferior frontal gyrus and the bilateral
      medial frontal gyrus are the most consistent neural correlates of category
      typicality that persist across languages and linguistic cues. These data together
      suggest that both cross- and within-language differences in the explicitness of
      category information have strong effects on the nature of categorization
      processes performed by the brain. 

PMID- 24135132
TI  - Gamma- and theta-band synchronization during semantic priming reflect local and
      long-range lexical-semantic networks.
AB  - Anterior and posterior brain areas are involved in the storage and retrieval of
      semantic representations, but it is not known how these areas dynamically
      interact during semantic processing. We hypothesized that long-range theta-band
      coherence would reflect coupling of these areas and examined the oscillatory
      dynamics of lexical-semantic processing using a semantic priming paradigm with a
      delayed letter-search task while recording subjects' EEG. Time-frequency analysis
      revealed facilitation of semantic processing for Related compared to Unrelated
      conditions, which resulted in a reduced N400 and reduced gamma power from 150 to
      450ms. Moreover, we observed greater anterior-posterior theta coherence for
      Unrelated compared to Related conditions over the time windows 150-425ms and 600
      900ms. We suggest that while gamma power reflects activation of local functional
      networks supporting semantic representations, theta coherence indicates dynamic
      coupling of anterior and posterior areas for retrieval and post-retrieval
      processing and possibly an interaction between semantic relatedness and working
      memory. 

PMID- 24135134
TI  - Cross-linguistic parallels in processing derivational morphology: evidence from
      Polish.
AB  - Neuroimaging evidence in English suggests that the neurocognitive processing of
      derivationally complex words primarily reflects their properties as whole forms.
      The current experiment provides a cross-linguistic examination of these proposals
      by investigating the processing of derivationally complex words in the rich
      morphological system of Polish. Within the framework of a dual language system
      approach, we asked whether there is evidence for decompositional processing of
      derivationally complex Polish stems - reflected in the activation of a
      linguistically specific decompositional system in the left hemisphere - or for
      increased competition between the derived stem and its embedded base stem in the
      bilateral system. The results showed activation in the bilateral system and no
      evidence for selective engagement of the left hemisphere decompositional system.
      This provides a cross-linguistic validation for the hypothesis that the
      neurocognitive processing of derived stems primarily reflects their properties as
      stored forms. 

PMID- 24135135
TI  - Tracking the clonal origin of lethal prostate cancer.
AB  - Recent controversies surrounding prostate cancer overtreatment emphasize the
      critical need to delineate the molecular features associated with progression to
      lethal metastatic disease. Here, we have used whole-genome sequencing and
      molecular pathological analyses to characterize the lethal cell clone in a
      patient who died of prostate cancer. We tracked the evolution of the lethal cell
      clone from the primary cancer to metastases through samples collected during
      disease progression and at the time of death. Surprisingly, these analyses
      revealed that the lethal clone arose from a small, relatively low-grade cancer
      focus in the primary tumor, and not from the bulk, higher-grade primary cancer or
      from a lymph node metastasis resected at prostatectomy. Despite being limited to
      one case, these findings highlight the potential importance of developing and
      implementing molecular prognostic and predictive markers, such as alterations of
      tumor suppressor proteins PTEN or p53, to augment current pathological evaluation
      and delineate clonal heterogeneity. Furthermore, this case illustrates the
      potential need in precision medicine to longitudinally sample metastatic lesions
      to capture the evolving constellation of alterations during progression. Similar
      comprehensive studies of additional prostate cancer cases are warranted to
      understand the extent to which these issues may challenge prostate cancer
      clinical management. 

PMID- 24135136
TI  - Itch expression by Treg cells controls Th2 inflammatory responses.
AB  - Regulatory T (Treg) cells maintain immune homeostasis by limiting autoimmune and
      inflammatory responses. Treg differentiation, maintenance, and function are
      controlled by the transcription factor Foxp3. However, the exact molecular
      mechanisms underlying Treg cell regulation remain elusive. Here, we show that
      Treg cell-specific ablation of the E3 ubiquitin ligase Itch in mice caused
      massive multiorgan lymphocyte infiltration and skin lesions, chronic T cell
      activation, and the development of severe antigen-induced airway inflammation.
      Surprisingly, Foxp3 expression, homeostasis, and the in vitro and in vivo
      suppressive capability of Treg cells were not affected by Itch deficiency. We
      found that the expression of Th2 cytokines by Treg cells was increased in the
      absence of Itch. Fate mapping revealed that a fraction of Treg cells lost Foxp3
      expression independently of Itch. However, Th2 cytokines were excessively
      augmented in Itch(-/-) Foxp3-negative "ex-Treg" cells without altering the
      percentage of conversion. Targeted knockdown of Th2 transcriptional regulators in
      Itch(-/-) Treg cells prevented Th2 cytokine production. The present study unveils
      a mechanism of Treg cell acquisition of Th2-like properties that is independent
      of Foxp3 function and Treg cell stability.

PMID- 24135137
TI  - A nonclassical vitamin D receptor pathway suppresses renal fibrosis.
AB  - The TGF-beta superfamily comprises pleiotropic cytokines that regulate SMAD and
      non-SMAD signaling. TGF-beta-SMAD signal transduction is known to be involved in
      tissue fibrosis, including renal fibrosis. Here, we found that 1,25
      dihydroxyvitamin D3-bound [1,25(OH)2D3-bound] vitamin D receptor (VDR)
      specifically inhibits TGF-beta-SMAD signal transduction through direct
      interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH)2D3 treatment
      prevented renal fibrosis through the suppression of TGF-beta-SMAD signal
      transduction. Based on the structure of the VDR-ligand complex, we generated 2
      synthetic ligands. These ligands selectively inhibited TGF-beta-SMAD signal
      transduction without activating VDR-mediated transcription and significantly
      attenuated renal fibrosis in mice. These results indicate that 1,25(OH)2D3
      dependent suppression of TGF-beta-SMAD signal transduction is independent of VDR
      mediated transcriptional activity. In addition, these ligands did not cause
      hypercalcemia resulting from stimulation of the transcriptional activity of the
      VDR. Thus, our study provides a new strategy for generating chemical compounds
      that specifically inhibit TGF-beta-SMAD signal transduction. Since TGF-beta-SMAD
      signal transduction is reportedly involved in several disorders, our results will
      aid in the development of new drugs that do not cause detectable adverse effects,
      such as hypercalcemia. 

PMID- 24135138
TI  - Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced
      thyroid cancers.
AB  - Exposure to ionizing radiation during childhood markedly increases the risk of
      developing papillary thyroid cancer. We examined tissues from 26 Ukrainian
      patients with thyroid cancer who were younger than 10 years of age and living in
      contaminated areas during the time of the Chernobyl nuclear reactor accident. We
      identified nonoverlapping somatic driver mutations in all 26 cases through
      candidate gene assays and next-generation RNA sequencing. We found that 22 tumors
      harbored fusion oncogenes that arose primarily through intrachromosomal
      rearrangements. Altogether, 23 of the oncogenic drivers identified in this cohort
      aberrantly activate MAPK signaling, including the 2 somatic rearrangements
      resulting in fusion of transcription factor ETS variant 6 (ETV6) with
      neurotrophic tyrosine kinase receptor, type 3 (NTRK3) and fusion of acylglycerol
      kinase (AGK) with BRAF. Two other tumors harbored distinct fusions leading to
      overexpression of the nuclear receptor PPARgamma. Fusion oncogenes were less
      prevalent in tumors from a cohort of children with pediatric thyroid cancers that
      had not been exposed to radiation but were from the same geographical regions.
      Radiation-induced thyroid cancers provide a paradigm of tumorigenesis driven by
      fusion oncogenes that activate MAPK signaling or, less frequently, a PPARgamma
      driven transcriptional program. 

PMID- 24135139
TI  - Essential amino acid supplementation in patients following total knee
      arthroplasty.
AB  - BACKGROUND: By the year 2030, 3.48 million older U.S. adults are projected to
      undergo total knee arthroplasty (TKA). Following this surgery, considerable
      muscle atrophy occurs, resulting in decreased strength and impaired functional
      mobility. Essential amino acids (EAAs) have been shown to attenuate muscle loss
      during periods of reduced activity and may be beneficial for TKA patients.
      METHODS: We used a double-blind, placebo-controlled, randomized clinical trial
      with 28 older adults undergoing TKA. Patients were randomized to ingest either 20
      g of EAAs (n = 16) or placebo (n = 12) twice daily between meals for 1 week
      before and 2 weeks after TKA. At baseline, 2 weeks, and 6 weeks after TKA, an MRI
      was performed to determine mid-thigh muscle and adipose tissue volume. Muscle
      strength and functional mobility were also measured at these times. RESULTS: TKA
      patients receiving placebo exhibited greater quadriceps muscle atrophy, with a 
      14.3 +/- 3.6% change from baseline to 2 weeks after surgery compared with -3.4 +/
      3.1% for the EAA group (F = 5.16, P = 0.036) and a -18.4 +/- 2.3% change from
      baseline to 6 weeks after surgery for placebo versus -6.2 +/- 2.2% for the EAA
      group (F = 14.14, P = 0.001). EAAs also attenuated atrophy in the nonoperated
      quadriceps and in the hamstring and adductor muscles of both extremities. The EAA
      group performed better at 2 and 6 weeks after surgery on functional mobility
      tests (all P < 0.05). Change in quadriceps muscle atrophy was significantly
      associated with change in functional mobility (F = 5.78, P = 0.021). CONCLUSION:
      EAA treatment attenuated muscle atrophy and accelerated the return of functional
      mobility in older adults following TKA. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00760383.

PMID- 24135140
TI  - Developmental and tumoral vascularization is regulated by G protein-coupled
      receptor kinase 2.
AB  - Tumor vessel dysfunction is a pivotal event in cancer progression. Using an in
      vivo neovascularization model, we identified G protein-coupled receptor kinase 2
      (GRK2) as a key angiogenesis regulator. An impaired angiogenic response involving
      immature vessels was observed in mice hemizygous for Grk2 or in animals with
      endothelium-specific Grk2 silencing. ECs isolated from these animals displayed
      intrinsic alterations in migration, TGF-beta signaling, and formation of tubular
      networks. Remarkably, an altered pattern of vessel growth and maturation was
      detected in postnatal retinas from endothelium-specific Grk2 knockout animals.
      Mouse embryos with systemic or endothelium-selective Grk2 ablation had marked
      vascular malformations involving impaired recruitment of mural cells. Moreover,
      decreased endothelial Grk2 dosage accelerated tumor growth in mice, along with
      reduced pericyte vessel coverage and enhanced macrophage infiltration, and this
      transformed environment promoted decreased GRK2 in ECs and human breast cancer
      vessels. Our study suggests that GRK2 downregulation is a relevant event in the
      tumoral angiogenic switch. 

PMID- 24135141
TI  - AMPK dysregulation promotes diabetes-related reduction of superoxide and
      mitochondrial function.
AB  - Diabetic microvascular complications have been considered to be mediated by a
      glucose-driven increase in mitochondrial superoxide anion production. Here, we
      report that superoxide production was reduced in the kidneys of a steptozotocin
      induced mouse model of type 1 diabetes, as assessed by in vivo real-time
      transcutaneous fluorescence, confocal microscopy, and electron paramagnetic
      resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of
      pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice. These
      observations were consistent with an overall reduction of mitochondrial glucose
      oxidation. Activity of AMPK, the major energy-sensing enzyme, was reduced in
      kidneys from both diabetic mice and humans. Mitochondrial biogenesis, PDH
      activity, and mitochondrial complex activity were rescued by treatment with the
      AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
      AICAR treatment induced superoxide production and was linked with glomerular
      matrix and albuminuria reduction in the diabetic kidney. Furthermore, diabetic
      heterozygous superoxide dismutase 2 (Sod2(+/-)) mice had no evidence of increased
      renal disease, and Ampka2(-/-) mice had increased albuminuria that was not
      reduced with AICAR treatment. Reduction of mitochondrial superoxide production
      with rotenone was sufficient to reduce AMPK phosphorylation in mouse kidneys.
      Taken together, these results demonstrate that diabetic kidneys have reduced
      superoxide and mitochondrial biogenesis and activation of AMPK enhances
      superoxide production and mitochondrial function while reducing disease activity.

PMID- 24135142
TI  - Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix.
AB  - The use of induced pluripotent stem cells (iPSCs) has been postulated to be the
      most effective strategy for developing patient-specific respiratory epithelial
      cells, which may be valuable for lung-related cell therapy and lung tissue
      engineering. We generated a relatively homogeneous population of alveolar
      epithelial type II (AETII) and type I (AETI) cells from human iPSCs that had
      phenotypic properties similar to those of mature human AETII and AETI cells. We
      used these cells to explore whether lung tissue can be regenerated in vitro.
      Consistent with an AETII phenotype, we found that up to 97% of cells were
      positive for surfactant protein C, 95% for mucin-1, 93% for surfactant protein B,
      and 89% for the epithelial marker CD54. Additionally, exposing induced AETII to a
      Wnt/beta-catenin inhibitor (IWR-1) changed the iPSC-AETII-like phenotype to a
      predominantly AETI-like phenotype. We found that of induced AET1 cells, more than
      90% were positive for type I markers, T1alpha, and caveolin-1. Acellular lung
      matrices were prepared from whole rat or human adult lungs treated with
      decellularization reagents, followed by seeding these matrices with alveolar
      cells derived from human iPSCs. Under appropriate culture conditions, these
      progenitor cells adhered to and proliferated within the 3D lung tissue scaffold
      and displayed markers of differentiated pulmonary epithelium. 

PMID- 24135144
TI  - "N of 1" case reports in the era of whole-genome sequencing.
AB  - Prostate cancer has a range of clinical outcomes, from complete remission in
      response to treatment to death as a result of aggressive metastasis. Prognosis
      for individuals with prostate cancer is not readily predictable, and new
      diagnostics will be useful for treatment strategy determination. In this issue of
      the JCI, Haffner and colleagues use comprehensive tumor genome sequencing to
      investigate the origin of genetic mutations underlying a case of lethal prostate
      cancer. Surprisingly, the lethal clone in this individual arose from a tumor
      focus that is typically considered very low risk based on histology. Their report
      highlights the need to collect and curate "N of 1" cases to develop a database
      that can be used for clinical decision making. 

PMID- 24135143
TI  - Mitochondrial ROS deficiency and diabetic complications: AMP[K]-lifying the
      adaptation to hyperglycemia.
AB  - Global, sustained production of ROS has deleterious effects on tissue structure
      and function and gives rise to biochemical and physiological changes associated
      with organ senescence. Specific, localized ROS metabolites generated by
      mitochondria and NADPH oxidases also transduce homeostatic information in
      response to metabolic, mechanical, and inflammatory cues. In this issue of the
      JCI, Dugan and colleagues demonstrate that mitochondrial-derived ROS, which is
      maintained by a feed-forward AMP kinase activation cascade, is reduced in
      diabetes and plays an adaptive role in preserving renal glomerular function
      during hyperglycemia. This enlightened view of mitochondrial ROS biology forces
      us to reconsider therapeutic approaches to metabolic disease complications such
      as diabetic nephropathy. 

PMID- 24135145
TI  - Transmission of methicillin-resistant Staphylococcus aureus isolates on broiler
      farms.
AB  - The aim of the present study was to investigate the resistance pheno- and
      genotypes and the molecular typing characteristics of methicillin-resistant
      Staphylococcus aureus (MRSA) isolates from broiler farms in order to explore
      transmission between the different reservoirs. Thirty-seven MRSA CC398 isolates
      (11 from broilers, 15 from the broiler houses, 5 from farm residences and 6 from
      humans living and/or working on the farms) cultured from samples at four
      different farms during a previous study, were included. In addition to the
      previously determined spa types, the isolates were characterized by dru typing,
      SCCmec typing, pulsed-field gel electrophoresis and DNA microarray. Resistance
      phenotypes were determined by broth microdilution. Resistance genes were detected
      by DNA microarray or specific PCR assays. Selected isolates from broilers and
      humans (n=7) were analysed by whole genome mapping. On the same farm, isolates
      from chickens, broiler houses, the farm residences and humans were often closely
      related or indistinguishable. On three of the four farms, however, MRSA isolates
      with different characteristics were present. On the one hand, the apparent
      similarity of MRSA isolates from the same farm indicates transmission between
      broilers, humans and their environment. On the other hand, different MRSA
      isolates were present on the same farm, indicating introduction from different
      sources or diversification over time. This study shows that different typing
      methods should be used to investigate epidemiological links between isolates and
      that whole genome mapping can be a useful tool to establish these links. 

PMID- 24135146
TI  - Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast
      cancer.
AB  - Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T
      DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable
      linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies
      demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1
      to the HER2-positive (HER2(+)) tumor cell combined with trastuzumab's activation
      of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated
      signal transduction. In phase II studies, T-DM1 was active in patients with
      trastuzumab- and lapatinib-refractory metastatic breast cancer and led to
      improved progression-free survival compared with the combination of trastuzumab
      and docetaxel in the first-line setting. In a recent phase III trial in patients
      with metastatic breast cancer who previously received trastuzumab and a taxane, T
      DM1 resulted in improved progression-free and overall survival compared with
      capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity
      profile; reversible thrombocytopenia and hepatic transaminase elevations are the
      only grade >=3 adverse event present in 5% or more of patients. Alopecia,
      peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of
      its improved efficacy and toxicity compared with capecitabine/lapatinib, T-DM1
      should be considered the standard for patients with HER2(+) metastatic breast
      cancer who have previously progressed on trastuzumab and a taxane. Results from
      additional randomized studies in metastatic breast cancer are pending, and trials
      in the (neo)adjuvant setting are being initiated.

PMID- 24135147
TI  - Learning curve for paramedic endotracheal intubation and complications.
AB  - BACKGROUND: Pre-hospital laryngoscopic endotracheal intubation (ETI) is
      potentially a life-saving procedure but is a technique difficult to acquire. This
      study aimed to obtain a recommendation for the number of times ETI should be
      practiced by constructing the learning curve for endotracheal intubation by
      paramedics, as well as to report the change in the frequency of complications
      possibly associated with intubation over the training period. METHODS: Under
      training conditions, 32 paramedics performed a total of 1,045 ETIs in an
      operating room. Trainees performed ETIs until they succeeded in 30 cases. For
      each patient, the number of laryngoscopic maneuvers and any complications
      potentially associated with ETI were recorded. We built a generalized logistic
      model to construct the learning curve for ETI and the frequency of complications.
      RESULTS: During the training on the first 30 patients the rate of ETI success at
      the first attempt improved from 71% to 87%, but there was little improvement
      during the first 13 cases. The frequency of complications decreased from 53% to
      31%. More laryngoscopic maneuvers and longer operation time increased
      complications. CONCLUSIONS: It seems that 30 live experiences of performing an
      ETI is sufficient for obtaining a 90% ETI success rate, but there seems to be
      little benefit with fewer than 13 experiences. The frequency of complications
      remained at a high level even after the training. It is desirable to conduct a
      more detailed and rigorous evaluation of the benefit of pre-hospital ETI by
      controlling for the skill level of paramedics.

PMID- 24135148
TI  - Gallbladder complications associated with molecular targeted therapies: clinical
      and imaging features.
AB  - OBJECTIVES: To evaluate the clinical and imaging features of molecular target
      therapies (MTT)-associated gallbladder complications. METHODS: The clinical
      presentation, imaging features, management, and outcome in six consecutive
      patients, who developed gallbladder complications while on monotherapy with MTT,
      were studied. RESULTS: Imaging features included gallbladder distension, edema,
      hyperemia, pericholecystic fluid, and stranding. Two of the six patients were
      asymptomatic and continued the drug due to good response. Four of the six
      patients developed acute cholecystitis and required drug discontinuation
      temporarily or permanently with 2/4 patients requiring surgery. CONCLUSION: MTT
      can be associated with gallbladder complications that may need temporary or
      permanent discontinuation of the associated drug.

PMID- 24135149
TI  - Cellular mechanics of germ band retraction in Drosophila.
AB  - Germ band retraction involves a dramatic rearrangement of the tissues on the
      surface of the Drosophila embryo. As germ band retraction commences, one tissue,
      the germ band, wraps around another, the amnioserosa. Through retraction the two
      tissues move cohesively as the highly elongated cells of the amnioserosa contract
      and the germ band moves so it is only on one side of the embryo. To understand
      the mechanical drivers of this process, we designed a series of laser ablations
      that suggest a mechanical role for the amnioserosa. First, we find that during
      mid retraction, segments in the curve of the germ band are under anisotropic
      tension. The largest tensions are in the direction in which the amnioserosa
      contracts. Second, ablating one lateral flank of the amnioserosa reduces the
      observed force anisotropy and leads to retraction failures. The other intact
      flank of amnioserosa is insufficient to drive retraction, but can support some
      germ band cell elongation and is thus not a full phenocopy of ush mutants.
      Another ablation-induced failure in retraction can phenocopy mys mutants, and
      does so by targeting amnioserosa cells in the same region where the mutant fails
      to adhere to the germ band. We conclude that the amnioserosa must play a key, but
      assistive, mechanical role that aids uncurling of the germ band. 

PMID- 24135150
TI  - Appropriate evidence sources for populating decision analytic models within
      health technology assessment (HTA): a systematic review of HTA manuals and health
      economic guidelines.
AB  - BACKGROUND: An increasing number of evidence sources are relevant for populating
      decision analytic models. What is needed is detailed methodological advice on
      which type of data is to be used for what type of model parameter. PURPOSE: We
      aim to identify standards in health technology assessment manuals and economic
      (modeling) guidelines on appropriate evidence sources and on the role different
      types of data play within a model. METHODS: Documents were identified via a call
      among members of the International Network of Agencies for Health Technology
      Assessment and by hand search. We included documents from Europe, the United
      States, Canada, Australia, and New Zealand as well as transnational guidelines
      written in English or German. We systematically summarized in a narrative manner
      information on appropriate evidence sources for model parameters, their
      advantages and limitations, data identification methods, and data quality issues.
      RESULTS: A large variety of evidence sources for populating models are mentioned
      in the 28 documents included. They comprise research- and non-research-based
      sources. Valid and less appropriate sources are identified for informing
      different types of model parameters, such as clinical effect size, natural
      history of disease, resource use, unit costs, and health state utility values.
      Guidelines do not provide structured and detailed advice on this issue.
      LIMITATIONS: The article does not include information from guidelines in
      languages other than English or German, and the information is not tailored to
      specific modeling techniques. CONCLUSIONS: The usability of guidelines and
      manuals for modeling could be improved by addressing the issue of evidence
      sources in a more structured and comprehensive format.

PMID- 24135151
TI  - Use of TissuePatchTM sealant film in the management of chyle leak in major neck
      surgery.
AB  - Chylous fistula is rare, and operation is often required for high output fistulas
      after serious operations on the neck. TissuePatchTMsealant film (Tissuemed Ltd.,
      Leeds, UK) is a useful adjunct to ensure that potential sources of leakage are
      sealed effectively.

PMID- 24135152
TI  - Prenatal detection of fetal triploidy from cell-free DNA testing in maternal
      blood.
AB  - OBJECTIVE: To investigate potential performance of cell-free DNA (cfDNA) testing
      in maternal blood in detecting fetal triploidy. METHODS: Plasma and buffy coat
      samples obtained at 11-13 weeks' gestation from singleton pregnancies with
      diandric triploidy (n=4), digynic triploidy (n=4), euploid fetuses (n=48) were
      sent to Natera, Inc. (San Carlos, Calif., USA) for cfDNA testing. Multiplex
      polymerase chain reaction amplification of cfDNA followed by sequencing of single
      nucleotide polymorphic loci covering chromosomes 13, 18, 21, X, and Y was
      performed. Sequencing data were analyzed using the NATUS algorithm which
      identifies copy number for each of the five chromosomes. RESULTS: cfDNA testing
      provided a result in 44 (91.7%) of the 48 euploid cases and correctly predicted
      the fetal sex and the presence of two copies each of chromosome 21, 18 and 13. In
      diandric triploidy, cfDNA testing identified multiple paternal haplotypes
      (indicating fetal trisomy 21, trisomy 18 and trisomy 13) suggesting the presence
      of either triploidy or dizygotic twins. In digynic triploidy the fetal fraction
      corrected for maternal weight and gestational age was below the 0.5th percentile.
      CONCLUSIONS: cfDNA testing by targeted sequencing and allelic ratio analysis of
      single nucleotide polymorphisms covering chromosomes 21, 18, 13, X, and Y can
      detect diandric triploidy and raise the suspicion of digynic triploidy.

PMID- 24135153
TI  - Medical students' attitudes toward people with dementia: an international
      investigation.
AB  - BACKGROUND: The changing demographics of societies mean that medical students
      worldwide must be sufficiently prepared to care competently for patients with
      dementia through development of appropriate knowledge, skills, and attitudes. No
      previous research had explored undergraduate medical students' attitudes toward
      people with dementia. METHODS: An adapted version of the Approaches to Dementia
      Questionnaire (ADQ) was completed by 501 medical undergraduates in years 1, 3,
      and 5 of their degree programs in the UK and Malaysia. Non-parametric statistical
      analysis focused on any differences between year groups and geographical
      locations. RESULTS: The mean ADQ response indicated a generally positive attitude
      across the sample, comparable with other healthcare professionals previously
      surveyed. Year 3 and year 5 students expressed significantly more positive
      attitudes than year 1 students. Year 1 students based in the UK expressed
      significantly more positive attitudes than year 1 student based in Malaysia, but
      there were no significant differences between year 3 students based in different
      locations. CONCLUSION: The more positive attitudes found amongst year 3 and year
      5 students compared to year 1 may be a result of teaching emphasizing a person
      centered approach. The differences between entry-level students from Malaysia and
      the UK may reflect variance in cultural norms and expectations, or the ADQ's
      "Western" origin. Medical schools aiming to equip students with dementia-specific
      skills and knowledge can draw on the generally positive attitudes found in this
      study.

PMID- 24135154
TI  - Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated
      radiation therapy for localized prostate cancer.
AB  - Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for
      localized prostate cancer were evaluated. A total of 259 patients treated with 5
      field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated
      with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy
      (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily
      fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2
      Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54
      82) and the follow-up period for living patients was 47 months (range, 18-97).
      Androgen deprivation therapy was given according to patient risk. The overall and
      biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years
      in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at
      2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk
      patients in all groups was 89% at 4 years. Incidences of Grade >= 2 acute
      genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group,
      and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade >= 2 late
      gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1
      Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far,
      this stepwise shortening of treatment periods seems to be successful.

PMID- 24135155
TI  - 25-Hydroxyvitamin D and cognitive performance in mid-life.
AB  - Hypovitaminosis D has been linked with poor cognitive function, particularly in
      older adults, but studies lack a lifespan approach; hence, the effects of reverse
      causality remain unknown. In the present study, we aimed to assess the
      relationship between 25-hydroxyvitamin D (25(OH)D) concentrations and subsequent
      cognitive performance in mid-adulthood and the influence of earlier life factors,
      including childhood cognitive ability, on this association. Information for the
      present study was obtained from the members of the 1958 British birth cohort (n
      6496). Serum 25(OH)D concentration, indicating vitamin D status, was measured at
      age 45 years. Verbal memory (immediate and delayed word recall), verbal fluency
      (animal naming) and speed of processing were tested at age 50 years. Information
      on childhood cognitive ability, educational attainment, vitamin D-related
      behaviours and other covariates was collected prospectively from participants
      throughout their life. Childhood cognitive ability and educational attainment by
      age 42 years were strongly correlated with cognitive performance at age 50 years
      and with several vitamin D-related behaviours in mid-adulthood, but not with
      25(OH)D concentrations at age 45 years. Participants with both low (<25 nmol/l)
      and high (>=75 nmol/l) 25(OH)D concentrations at age 45 years performed
      significantly worse on immediate word recall. The associations attenuated after
      adjustment for childhood cognitive ability, education, and socio-economic
      position; however, for the immediate word recall test, there was a non-linear
      association with 25(OH)D after further adjustment for obesity, menopausal status,
      smoking, alcohol consumption, physical activity and depressive symptoms at age 45
      years (P(curvature)=0.01). The present study demonstrated that 25(OH)D
      concentrations were non-linearly associated with immediate word recall in mid
      life. A clarification of the level of 25(OH)D concentrations that is most
      beneficial for predicting better cognitive performance in mid-life is required.

PMID- 24135156
TI  - Is morphokinetic analysis the answer?
AB  - Efforts aimed at improving pregnancy rates have focused on the search for
      additional markers of viability to supplement current criteria for embryo
      selection. Time-lapse technology represents a powerful tool in assisted
      reproduction for evaluating embryos dynamically. Whilst standard methods of
      embryo assessment are based on subjective morphology evaluation at discrete time
      points, thereby limiting the information produced for embryo selection, time
      lapse recording introduces several additional morphokinetic parameters for embryo
      evaluation. This additional information can improve implantation rates and
      reproductive outcomes. This review surveys available knowledge on time-lapse
      imaging to provide an overview of the advantages and applications of this
      technology.

PMID- 24135157
TI  - Preventing the transmission of mitochondrial DNA disorders: selecting the good
      guys or kicking out the bad guys.
AB  - Mitochondrial disorders represent the most common group of inborn errors of
      metabolism. Clinical manifestations can be extremely variable, ranging from
      single affected tissues to multisystemic syndromes. Maternally inherited
      mitochondrial DNA (mtDNA) mutations are a frequent cause, affecting about one in
      5000 individuals. The expression of mtDNA mutations differs from nuclear gene
      defects. Mutations are either homoplasmic or heteroplasmic, and in the latter
      case disease becomes manifest when the mutation load exceeds a tissue-specific
      threshold. Mutation load can vary between tissues and in time, and often an exact
      correlation between mutation load and clinical manifestations is lacking. Because
      of the possible clinical severity, the lack of treatment and the high recurrence
      risk of affected offspring for female carriers, couples request prevention of
      transmission of mtDNA mutations. Previously, choices have been limited due to a
      segregational bottleneck, which makes the mtDNA mutation load in embryos highly
      variable and the consequences largely unpredictable. However, recently it was
      shown that preimplantation genetic diagnosis offers a fair chance of unaffected
      offspring to carriers of heteroplasmic mtDNA mutations. Technically and ethically
      challenging possibilities, such maternal spindle transfer and pronuclear
      transfer, are emerging and providing carriers additional prospects of giving
      birth to a healthy child.

PMID- 24135158
TI  - The efficacy of Advantix(r) to prevent transmission of Ehrlichia canis to dogs by
      Rhipicephalus sanguineus ticks.
AB  - The capacity of a topical combination of imidacloprid and permethrin
      (Advantix((r))) to prevent transmission of Ehrlichia canis was studied in two
      groups of six dogs. One group served as controls, whereas the other group was
      treated. All dogs were exposed to E. canis-infected Rhipicephalus sanguineus
      ticks on Days 7, 14, 21 and Day 28 post acaricidal treatment. The adult R.
      sanguineus ticks were released into the individual kennels of the dogs to
      simulate natural tick exposure. In situ tick counts were conducted on Day 9, 16
      and 23 and any remaining ticks were counted and removed on Day 30. The efficacy
      of the acaricidal treatment against R. sanguineus ranged between 96.1% and 98.9%
      at 48 h post-application and lasted up to 4 weeks. Four out of six control dogs
      became infected with E. canis, as demonstrated by the presence of specific E.
      canis antibodies and the detection by PCR of E. canis DNA in blood samples. These
      dogs became thrombocytopenic and displayed fever and were consecutively rescue
      treated by doxycycline. None of the six treated dogs became infected with E.
      canis, as confirmed by the lack of specific antibodies and absence of E. canis
      DNA in blood samples. Advantix((r)) prevented transmission of E. canis and
      provided protection against monocytic ehrlichiosis for 4 weeks post acaricidal
      treatment.

PMID- 24135159
TI  - Non-contact heart rate monitoring utilizing camera photoplethysmography in the
      neonatal intensive care unit - a pilot study.
AB  - BACKGROUND: Presently the heart rate is monitored in the Neonatal Intensive Care
      Unit with contact sensors: electrocardiogram or pulse oximetry. These techniques
      can cause injuries and infections, particularly in very premature infants with
      fragile skin. Camera based plethysmography was recently demonstrated in adults as
      a contactless method to determine heart rate. AIM: To investigate the feasibility
      of this technique for NICU patients and identify challenging conditions. STUDY
      DESIGN AND PARTICIPANTS: Video recordings using only ambient light were made of
      19 infants at two NICUs in California and The Netherlands. Heart rate can be
      derived from these recordings because each cardiovascular pulse wave induces
      minute pulsatile skin color changes, invisible to the eye but measurable with a
      camera. RESULTS: In all infants the heart beat induced photoplethysmographic
      signal was strong enough to be measured. Low ambient light level and infant
      motion prevented successful measurement from time to time. CONCLUSIONS:
      Contactless heart rate monitoring by means of a camera using ambient light was
      demonstrated for the first time in the NICU population and appears feasible.
      Better hardware and improved algorithms are required to increase robustness.

PMID- 24135164
TI  - Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility
      to steroid-induced osteonecrosis of the femoral head in Chinese population.
AB  - BACKGROUND: Steroid usage has been considered as a leading cause of non-traumatic
      osteonecrosis of the femoral head (ONFH), which is involved in hypo-fibrinolysis
      and blood supply interruption. Genetic polymorphisms in plasminogen activator
      inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in
      several populations. However, this relationship has not been established in
      Chinese population. The aim of this study was to investigate the association of
      PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese
      population. METHODS: A case-control study was conducted, which included 94 and
      106 unrelated patients after steroid administration recruited from 14 provinces
      in China, respectively. Two SNPs (rs11178 and rs2227631) within PAI-1 were
      genotyped using Sequenom MassARRAY system. RESULTS: rs2227631 SNP was
      significantly associated with steroid-induced ONFH group in codominant (P = 0.04)
      and recessive (P = 0.02) models. However, there were no differences found in
      genotype frequencies of rs11178 SNP between controls and patients with steroid
      induced ONFH (all P > 0.05). CONCLUSIONS: Our data offer the convincing evidence
      for the first time that rs2227631 SNP of PAI-1 may be associated with the risk of
      steroid-induced ONFH, suggesting that the genetic variations of this gene may
      play an important role in the disease development. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1569909986109783.

PMID- 24135165
TI  - Spatio-temporal analysis of shrinkage vectors during photo-polymerization of
      composite.
AB  - OBJECTIVES: The purpose of this study was to validate a new method to investigate
      the polymerization shrinkage vectors of composite during light curing and to
      evaluate the overall utility and significance of the technique. METHODS: An
      optical instrument was developed to measure the location and direction of the
      polymerization shrinkage strain vectors of dental composite during light curing
      using a particle tracking method with computer vision. The measurement system
      consisted of a CCD color camera, a lens and a filter, and software for multi
      particle tracking. A universal hybrid composite (Z250, 3M ESPE, St. Paul MN, USA)
      was molded into thin disk-shaped specimens (un-bonded and bonded) or filled into
      a cavity within a tooth slab (bonded). The composite surface was coated with
      fluorescent particles prior to light curing. The images of the fluorescent
      particles were stored at 2 frames/s for 10 min, and the movements of the
      particles on the composite surface were tracked with computer vision during
      curing. The polymerization shrinkage strain vectors as a function of time and
      location were analyzed. The volume shrinkage of the composite was also measured
      for comparison. RESULTS: The linear and volume shrinkage of the composite at 10
      min were 0.75 (0.12)% and 2.26 (0.18)%, respectively. The polymerization
      shrinkage vectors were directed toward the center of the specimen and were
      isotropic in all directions when the composite was allowed to shrinkage freely
      without bonding. In contrast, the shrinkage vectors were directed toward the
      bonding surface and were anisotropic when the composite was bonded to a fixed
      wall. The regional displacement vectors of composite in a tooth cavity were
      dependent on the location, depth and time. SIGNIFICANCE: The new instrument was
      able to measure the regional linear shrinkage strain vectors over an entire
      surface of a composite specimen as a function of time and location. Therefore,
      this instrument can be used to characterize the shrinkage behaviors for a wide
      range of commercial and experimental visible-light-cure materials in relation to
      the composition, boundary condition and cavity geometry.

PMID- 24135166
TI  - Knowledge-based automated reconstruction of human brain white matter tracts using
      a path-finding approach with dynamic programming.
AB  - It has been shown that the anatomy of major white matter tracts can be delineated
      using diffusion tensor imaging (DTI) data. Tract reconstruction, however, often
      suffers from a large number of false-negative results when a simple line
      propagation algorithm is used. This limits the application of this technique to
      only the core of prominent white matter tracts. By employing probabilistic path
      generation algorithms, connectivity between a larger number of anatomical regions
      can be studied, but an increase in the number of false-positive results is
      inevitable. One of the causes of the inaccuracy is the complex axonal anatomy
      within a voxel; however, high-angular resolution (HAR) methods have been proposed
      to ameliorate this limitation. However, HAR data are relatively rare due to the
      long scan times required and the low signal-to-noise ratio. In this study, we
      tested a probabilistic path-finding method in which two anatomical regions with
      known connectivity were pre-defined and a path that maximized agreement with the
      DTI data was searched. To increase the accuracy of the trajectories, knowledge
      based anatomical constraints were applied. The reconstruction protocols were
      tested using DTI data from 19 normal subjects to examine test-retest
      reproducibility and cross-subject variability. Fifty-two tracts were found to be
      reliably reconstructed using this approach, which can be viewed on our website. 

PMID- 24135167
TI  - Task modulations of racial bias in neural responses to others' suffering.
AB  - Recent event related brain potential research observed a greater frontal activity
      to pain expressions of racial in-group than out-group members and such racial
      bias in neural responses to others' suffering was modulated by task demands that
      emphasize race identity or painful feeling. However, as pain expressions activate
      multiple brain regions in the pain matrix, it remains unclear which part of the
      neural circuit in response to others' suffering undergoes modulations by task
      demands. We scanned Chinese adults, using functional MRI, while they categorized
      Asian and Caucasian faces with pain or neutral expressions in terms of race or
      identified painful feelings of each individual face. We found that pain vs.
      neutral expressions of Asian but not Caucasian faces activated the anterior
      cingulate (ACC) and anterior insular (AI) activity during race judgments.
      However, pain compared to race judgments increased ACC and AI activity to pain
      expressions of Caucasian but not Asian faces. Moreover, race judgments induced
      increased activity in the dorsal medial prefrontal cortex whereas pain judgments
      increased activity in the bilateral temporoparietal junction. The results suggest
      that task demands emphasizing an individual's painful feeling increase ACC/AI
      activities to pain expressions of racial out-group members and reduce the racial
      bias in empathic neural responses. 

PMID- 24135168
TI  - Cognitive architectures as a tool for investigating the role of oscillatory power
      and coherence in cognition.
AB  - In contrast to our increasing knowledge of the role that oscillations in single
      brain regions play in cognition, very little is known about how coherence between
      oscillations in distant brain regions is related to information transmission.
      Here I present a cognitive modeling approach that can address that question.
      Specifically, I show how a model of the attentional blink implemented in the ACT
      R cognitive architecture is related to the amplitude and coherence of EEG
      oscillations. The dynamics of the model's working memory resource is primarily
      associated with parietal 4-9 Hz theta oscillations, while the dynamics of the
      model's declarative memory, visual perception and procedural resources together
      are correlated with posterior theta oscillations. I further show that model
      predictions about inter-module communication during the processes of stimulus
      identification and target consolidation are associated with selective increases
      in coherence at the predicted points in time.

PMID- 24135169
TI  - Prevention & control of CVD in women & children in India.

PMID- 24135170
TI  - Potential for inhibition of bacterial efflux pumps in multidrug-resistant Vibrio
      cholera.

PMID- 24135171
TI  - Morbidity pattern of sickle cell disease in India: a single centre perspective.

PMID- 24135172
TI  - Long term non-progressor (LTNP) HIV infection.

PMID- 24135173
TI  - Tropical pulmonary eosinophilia--a review.
AB  - Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and
      eosiniphilia seen predominantly in the Indian subcontinent and other tropical
      areas. Its etiological link with Wuchereria bancrofti and Brugia malayi has been
      well established. The pathogenesis is due to an exaggerated immune response to
      the filarial antigens which includes type I, type III and type IV reactions with
      eosinophils playing a pivotal role. Peripheral blood eosinophilia is usually
      striking with levels over 3000/MUl being common. High serum levels of IgE and
      filarial-specific IgE and IgG are also found. The pathology may vary from an
      acute eosinophilic alveolitis to histiocytic infiltration depending on the stage
      of the disease. While earlier studies had suggested that the disease runs a
      benign course, more recent work has shown that untreated TPE could result in a
      fair degree of respiratory morbidity. Pulmonary function tests may show a mixed
      restrictive and obstructive abnormality with a reduction in diffusion capacity.
      The bronchoalveolar lavage (BAL) eosinophil count has a negative correlation with
      the diffusion capacity. Treatment consists of diethylcarbamazine (DEC) for at
      least three weeks. Despite treatment with DEC, about 20 per cent of patients may
      relapse. Steroids have shown to have a beneficial effect but the exact dose and
      duration is yet to be confirmed by randomized controlled trials. A specific and
      easily available marker is required for TPE in order to distinguish it from other
      parasitic and non-parasitic causes of pulmonary eosinophilia.

PMID- 24135174
TI  - Genital Chlamydia trachomatis: an update.
AB  - Chlamydia trachomatis is the most common cause of curable bacterial sexually
      transmitted infection (STI) worldwide. It manifests primarily as urethritis in
      males and endocervicitis in females. Untreated chlamydial infection in man can
      cause epididymitis and proctitis. Though most women with Chlamydia infection are
      asymptomatic or have minimal symptoms, some develop salpingitis, endometritis,
      pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor
      infertility. It is associated with an increased risk for the transmission or
      acquisition of HIV and is also attributed to be a risk factor for the development
      of cervical carcinoma. Early diagnosis and treatment of infected individuals is
      required to prevent the spread of the disease and severe sequelae. Traditionally,
      tissue culture was considered the gold standard for the diagnosis. However, with
      the availability of newer diagnostic techniques particularly molecular methods
      which are not only highly sensitive and specific but are cost-effective also, the
      diagnosis has became fast and easy. The purpose of this review is to study the
      various aspects of genital C. trachomatis infection. Also the advances related to
      the clinical picture, various diagnostic modalities, prevention, treatment, drug
      resistance and control measures will be dealt with. 

PMID- 24135175
TI  - Morbidity pattern in hospitalized under five children with sickle cell disease.
AB  - BACKGROUND & OBJECTIVES: Children with sickle cell disease require more frequent
      hospital care and younger children (<5 yr of age) are more vulnerable to
      mortality. There are limited data on the events leading to hospitalizations and
      death in younger children with sickle cell disease from India. This study was,
      therefore, undertaken to evaluate the morbidity pattern in hospitalized under
      five children with sickle cell disease in a tertiary care hospital in
      Maharashtra, India. METHODS: This was a prospective observational study carried
      out from July 2007 to June 2009. Hospitalized children below five years of age
      with sickle cell disease were enrolled for the study and evaluated for morbid
      event/s leading to hospitalization. Haematological indices were noted at baseline
      (most recent past when patient was not acutely sick) and at the time of
      hospitalization. RESULTS: Eighty five children with sickle cell disease were
      hospitalized during the study period. Hospitalization with acute febrile illness
      (31%) was the most common morbid event followed by severe anaemia (30%) and acute
      painful events (20%). Majority (62%) of the events occurred between August and
      October. Forty five patients had foetal haemoglobin (HbF) more than 20 per cent
      (26.80 +/- 4.81%) and morbidity was significantly less in these patients.
      INTERPRETATION & CONCLUSION: Acute febrile illness was the most common morbid
      event followed by severe anaemia and acute painful event hospitalized children
      with sickle cell disease. There was significant seasonal variation with maximum
      events occurring in the monsoon season.

PMID- 24135176
TI  - Factors associated with conversion of long-term non-progressors to progressors: a
      prospective study of HIV perinatally infected paediatric survivors.
AB  - BACKGROUND & OBJECTIVES: Survival pattern among children infected with the human
      immune deficiency virus (HIV) follows a bimodel distribution. Some children
      survive beyond 9 years age and are known as long term survivors (LTS) while
      others had a more rapid course to death during the first few years of life. In
      the LTS group of children, two sub-populations have emerged, the long term non
      progressors (LTNP) who have remained asymptomatic over a period of years and
      those who have survived despite clinical and laboratory evidence of disease
      progression, the long term progressors (LTP). The aim of the present study was to
      determine the factors influencing the conversion of LTNPs to LTPs in a group of
      perinatally HIV infected children who were followed up for five years. METHODS: A
      total of 26 HIV seropositive paediatric patients were monitored from 2006 to 2011
      with CD4 cell counts, onset of clinical manifestations, body weight, biochemical,
      haematological and immunological parameters. Statistical analyses, both
      qualitative and quantitative, were used to determine the degree of conversion of
      non-progressors to progressors. RESULTS: All 26 (13 female and 13 male)
      perinatally HIV infected children, born during 1991-1996 were healthy until 2006.
      But by 2011, 18 were placed in progressors group with antiretroviral therapy
      (ART), while six remained in non progressors group and two died. As per the
      Kaplan-Meier survival analysis, AIDS free median survival period (years) in LTP
      group (CD4 count) of the cohort was 10 +/- 0.66 (<200; P=<0.05); 11 +/- 0.61 (200
      350, P=<0.05), 12 +/- 0.18 (>350, P=<0.05). Intercurrent and opportunistic
      infections (OIs) were observed in LTPs only. The incidence of OI in LTPs was
      higher when compared to general paediatric population. INTERPRETATION &
      CONCLUSIONS: Our findings show that CD4 counts and OIs play an important role in
      influencing the survival chances of perinatally HIV infected children.

PMID- 24135177
TI  - Role of hepatitis B virus genotype D & its mutants in occult hepatitis B
      infection.
AB  - BACKGROUND & OBJECTIVES: Non-detection of hepatitis B virus (HBV) envelope
      protein (hepatitis B surface antigen, HBsAg) in a chronically HBV infected
      individual has been described as occult infection. One possible reason for this
      phenotype is alteration in large (L-HBsAg) to small (S-HBsAg) envelope protein
      ratio associated with reduced or non secretion of HBsAg. This results in
      quantitative levels of serum HBsAg below the detection limit of enzyme
      immunoassays. Genotype D of HBV has a characteristic 33 nucleotide (nt) deletion
      upstream of the pre-S2/S promoter. This deletion may reduce HBsAg secretion in
      occult infection patients infected with genotype D HBV. Additional deletions in
      the pre-S2/S promoter may further aggravate reduced HBsAg secretion in patients
      infected with genotype D HBV. Thus, the aim of the present study was to determine
      the role of genotype D specific 33nt deletion and additional pre-S2/S promoter
      deletions in causing reduced or no secretion of HBsAg, in occult infection. Since
      these deletions overlap virus polymerase, their effect on virus replication was
      also investigated. METHODS: We examined the in vitro expression of HBsAg, ratio
      of cure and 'e' antigen (HBcAg/HBeAg), their secretion and virus replication,
      using overlength 1.3 mer/1.86 mer genotype A replicons, and genotype D replicons
      with and without additional pre-S2/S promoter deletions from cases of occult
      infection. RESULTS: Genotype D replicon showed a decrease in HBsAg secretion
      compared to the wild-type genotype A. Genotype D replicons carrying additional
      pre-S2/S promoter deletions, showed further reduction in HBsAg secretion,
      demonstrated presence of intracellular HBcAg/HBeAg, virus replication
      intermediates and 'e' antigen secretion. INTERPRETATION & CONCLUSIONS: The
      characteristic 33 nt deletion of genotype D HBV reduces HBsAg secretion.
      Additional pre-S2/S promoter deletions may further diminish HBsAg secretion,
      leading to occult infection. Pre-S2/S promoter deletions do not affect HBV
      replication.

PMID- 24135178
TI  - Beneficiary level factors influencing Janani Suraksha Yojana utilization in urban
      slum population of trans-Yamuna area of Delhi.
AB  - BACKGROUND & OBJECTIVES: Janani Suraksha Yojana (JSY), a conditional cash
      transfer scheme introduced to improve the institutional delivery rates and
      thereby reduce the maternal and infant mortality was implemented in all States
      and Union Territories of India from 2007. The present study was carried out to
      identify the beneficiary level factors of utilization of JSY scheme in urban
      slums and resettlement colonies of trans-Yamuna area of Delhi. METHODS: A cross
      sectional community based survey was done of mothers of infants in the selected
      areas of the two districts by stratified random sampling on a population
      proportionate basis. Socio-demographic factors, antenatal services availed and
      distance of nearest health facility were studied. Outcome variable, a
      beneficiary, was a woman who had ever interacted with the ASHA of her area during
      the antenatal period of previous pregnancy and had child birth in an institution.
      Descriptive tables were drawn; univariate analysis followed by multiple logistic
      regression was applied for identifying the predictors for availing the benefits.
      RESULTS: Of the 469 mothers interviewed, 333 (71%) had institutional delivery,
      128 (27.3%) had benefited from JSY scheme and 68 (14.5%) had received cash
      benefits of JSY. Belonging to Hindu religion and having had more than 6 antenatal
      check ups were the significant predictors of availing the benefits of JSY.
      CONCLUSION: There is a need to improve the awareness among urban slum population
      about the utilization of JSY scheme. Targeting difficult to access areas with
      special measures and encouraging more antenatal visits were essential,
      prerequisites to improve the impact of JSY.

PMID- 24135179
TI  - Distribution, seasonal variation & dengue transmission prediction in Sisaket,
      Thailand.
AB  - BACKGROUND & OBJECTIVES: Environmental factors including weather variables may
      play a significant role in the transmission of dengue. This study investigated
      the effect of seasonal variation on the abundance of Aedes aegypti and Ae.
      albopictus larvae and explored the impact of weather variability on dengue
      transmission in Sisaket, Thailand. METHODS: The monthly mosquito larval surveys
      were carried out in urban and rural areas in Sisaket, Thailand from January to
      December 2010. Data on monthly-reported cases of dengue fever over the period
      2004-2010 were obtained from the Ministry of Public Health. Weather data over the
      same period were obtained from the Thai Meteorological Department. Chi-square
      test was used to find the differences relating to seasonal variability, areas of
      study, and mosquito species factors using entomological survey data. Time series
      Poisson regression analysis was performed using data on monthly weather variables
      and dengue cases. RESULTS: There were more Ae. aegypti larvae per household than
      Ae. albopictus larvae in the winter and rainy seasons. More Aedes larvae per
      household were found in the rainy season than in the winter and summer seasons.
      Relative humidity at a lag of one month and rainy days in the current month were
      significant predictors of dengue incidence in Sisaket. INTERPRETATION &
      CONCLUSIONS: Increased rain during the current month and less humidity during the
      previous month might trigger a higher incidence of dengue epidemic in Sisaket.
      The present findings suggest that the dengue incidence corresponds with the
      number of Aedes larvae. The seasonal patterns of dengue outbreaks coincide with
      the rainy season.

PMID- 24135180
TI  - Evaluation of vaginal pH for detection of bacterial vaginosis.
AB  - BACKGROUND & OBJECTIVES: Bacterial vaginosis (BV) is highly prevalent among women
      in reproductive age group. Little information exists on routine vaginal p H
      measurement in women with BV. We undertook this study to assess the utility of
      vaginal p H determination for initial evaluation of bacterial vaginosis. METHODS:
      In this cross-sectional study vaginal swabs were collected from women with
      complaints of white discharge, back ache and pain abdomen attending a government
      hospital and a community health clinic, and subjected to vaginal p H
      determination, Gram stain, wet mount and whiff test. Nugent score and Amsel
      criteria were used for BV confirmation. RESULTS: Of the 270 women included in the
      analysis, 154 had BV based on Nugents' score. The mean vaginal p H in women with
      BV measured by p H strips and p H glove was 5 and 4.9, respectively. The vaginal
      p H was significantly higher in women with BV. Vaginal discharge was prevalent in
      84.8 per cent women, however, only 56.8 per cent of these actually had BV by
      Nugent score (NS). Presence of clue cells and positive whiff test were
      significant for BV. Vaginal p H >4.5 by p H strips and p H Glove had a
      sensitivity of 72 and 79 per cent and specificity of 60 and 53 per cent,
      respectively to detect BV. Among the combination criteria, clue cells and glove p
      H >4.5 had highest sensitivity and specificity to detect BV. INTERPRETATION &
      CONCLUSIONS: Vaginal p H determination is relatively sensitive, but less specific
      in detecting women with BV. Inclusion of whiff test along with p H test reduced
      the sensitivity, but improved specificity. Both, the p H strip and p H glove are
      equally suitable for screening women with BV on outpatient basis.

PMID- 24135181
TI  - Referral patterns in de-addiction services: an experience from a single centre.

PMID- 24135182
TI  - Dual infection in human by Japanese encephalitis virus & chikungunya virus in
      Alappuzha district, Kerala, India.

PMID- 24135183
TI  - Seroprevalence of human immunodeficiency virus & hepatitis B virus co-infection
      in Belgaum, southern India.

PMID- 24135184
TI  - Gestational diabetes mellitus & associated risk factors.

PMID- 24135185
TI  - Stevens Johnson syndrome in a patient with HIV & visceral leishmaniasis.

PMID- 24135186
TI  - Patellar metastasis of melanoma.

PMID- 24135187
TI  - Food & nutrition security: challenges in the new millennium.
AB  - The World Food Summit in 1996 provided a comprehensive definition for food
      security which brings into focus the linkage between food, nutrition and health.
      India has been self sufficient in food production since seventies and low
      household hunger rates. India compares well with developing countries with
      similar health profile in terms of infant mortality rate (IMR) and under five
      mortality rate (U5 MR). India fares poorly when underweight in under five
      children is used as an indicator for food insecurity with rates comparable to
      that of Subsaharan Africa. If wasting [low body mass index (BMI) for age in
      children and low BMI in adults] which is closely related to adequacy of current
      food intake is used as an indictor for the assessment of household food security,
      India fares better. The nineties witnessed the emergence of dual nutrition burden
      with persistent inadequate dietary intake and undernutrition on one side and low
      physical activity / food intake above requirements and overnutrition on the other
      side. Body size and physical activity levels are two major determinants of human
      nutrient requirements. The revised recommended dietary allowances (RDA) for
      Indians takes cognisance of the current body weight and physical activity while
      computing the energy and nutrient requirements. As both under- and overnutrition
      are associated with health hazards, perhaps time has come for use of normal BMI
      as an indicator for food security. 

PMID- 24135188
TI  - Food production & availability--essential prerequisites for sustainable food
      security.
AB  - Food and nutrition security are intimately interconnected, since only a food
      based approach can help in overcoming malnutrition in an economically and
      socially sustainable manner. Food production provides the base for food security
      as it is a key determinant of food availability. This paper deals with different
      aspects of ensuring high productivity and production without associated
      ecological harm for ensuring adequate food availability. By mainstreaming
      ecological considerations in technology development and dissemination, we can
      enter an era of evergreen revolution and sustainable food and nutrition security.
      Public policy support is crucial for enabling this. 

PMID- 24135189
TI  - The changing nutrition scenario.
AB  - The past seven decades have seen remarkable shifts in the nutritional scenario in
      India. Even up to the 1950s severe forms of malnutrition such as kwashiorkar and
      pellagra were endemic. As nutritionists were finding home-grown and common-sense
      solutions for these widespread problems, the population was burgeoning and food
      was scarce. The threat of widespread household food insecurity and chronic
      undernutrition was very real. Then came the Green Revolution. Shortages of food
      grains disappeared within less than a decade and India became self-sufficient in
      food grain production. But more insidious problems arising from this revolution
      were looming, and cropping patterns giving low priority to coarse grains and
      pulses, and monocropping led to depletion of soil nutrients and 'Green Revolution
      fatigue'. With improved household food security and better access to health care,
      clinical manifestations of severe malnutrition virtually disappeared. But the
      decline in chronic undernutrition and "hidden hunger" from micronutrient
      deficiencies was slow. On the cusp of the new century, an added factor appeared
      on the nutritional scene in India. With steady urban migration, upward mobility
      out of poverty, and an increasingly sedentary lifestyle because of improvements
      in technology and transport, obesity rates began to increase, resulting in a dual
      burden. Measured in terms of its performance in meeting its Millennium
      Development Goals, India has fallen short. Despite its continuing high levels of
      poverty and illiteracy, India has a huge demographic potential in the form of a
      young population. This advantage must be leveraged by investing in nutrition
      education, household access to nutritious diets, sanitary environment and a
      health-promoting lifestyle. This requires co-operation from all the stakeholders,
      including governments, non government organizations, scientists and the people at
      large. 

PMID- 24135190
TI  - Rising food costs & global food security: key issues & relevance for India.
AB  - Rising food costs can have major impact on vulnerable households, pushing those
      least able to cope further into poverty and hunger. On the other hand, provided
      appropriate policies and infrastructure are in place, higher agricultural prices
      can also raise farmers' incomes and rural wages, improve rural economies and
      stimulate investment for longer-term economic growth. High food prices since 2007
      have had both short-term impacts and long-term consequences, both good and bad.
      This article reviews the evidence of how rising costs have affected global food
      security since the food price crisis of 2007-2008, and their impact on different
      categories of households and countries. In light of recent studies, we know more
      about how households, and countries, cope or not with food price shocks but a
      number of contentious issues remain. These include the adequacy of current
      estimates and the interpretation of national and household food and nutrition
      security indicators. India is a particularly important country in this regard,
      given the high number of food insecure, the relative weight of India in global
      estimates of food and nutrition insecurity, and the puzzles that remain
      concerning the country's reported declining per capita calorie consumption.
      Competing explanations for what is behind it are not in agreement, but these all
      point to the importance of policy and programme innovation and greater investment
      necessary to reach the achievable goal of food and nutrition security for all. 

PMID- 24135191
TI  - Massive dose vitamin A programme in India--need for a targeted approach.
AB  - The National Prophylaxis Programme against Nutritional Blindness due to vitamin A
      deficiency (NPPNB due to VAD) was started in 1970 with the specific aim of
      preventing nutritional blindness due to keratomalacia . The Programme was
      launched as an urgent remedial measure to combat the unacceptably high magnitude
      of xerophthalmic blindness in the country seen in the 1950s and 1960s. Clinical
      VAD has declined drastically during the last 40 years. Also, indicators of child
      health have shown substantial gains in different States in the country. The
      prevalence of severe undernutrition has come down significantly. Immunization
      coverage for measles and other vaccine preventable diseases has improved from 5-7
      per cent in early seventies to currently 60-90 per cent, in different States.
      Similarly, there has been a significant improvement in the overall dietary intake
      of young children. There has been virtual disappearance of keratomalacia, and a
      sharp decline in the prevalence of Bitot spots. Prophylactic mega dose
      administration of vitamin A is primarily advocated because of the claim of 23 per
      cent reduction in childhood mortality. However, benefits on this scale have been
      found only in areas with rudimentary health care facilities where clinical
      deficiency is common, and there is substantial heterogeneity, especially with
      inclusion of all trials. There is an urgent need for adopting a targeted rather
      than universal prophylactic mega dose vitamin A supplementation in preschool
      children. This approach is justified on the basis of currently available evidence
      documenting a substantial decline in VAD prevalence, substantial heterogeneity
      and uncertainty about mortality effects in present era with improved health care,
      and resource constraints with competing priorities. 

PMID- 24135192
TI  - Iodine deficiency disorders (IDD) control in India.
AB  - Iodine deficiency disorders (IDD) constitute the single largest cause of
      preventable brain damage worldwide. Majority of consequences of IDD are invisible
      and irreversible but at the same time these are preventable. In India, the entire
      population is prone to IDD due to deficiency of iodine in the soil of the
      subcontinent and consequently the food derived from it. To combat the risk of
      IDD, salt is fortified with iodine. However, an estimated 350 million people do
      not consume adequately iodized salt and, therefore, are at risk for IDD. Of the
      325 districts surveyed in India so far, 263 are IDD-endemic. The current
      household level iodized salt coverage in India is 91 per cent with 71 per cent
      households consuming adequately iodized salt. The IDD control goal in India was
      to reduce the prevalence of IDD below 10 per cent in the entire country by 2012.
      What is required is a "mission approach" with greater coordination amongst all
      stakeholders of IDD control efforts in India. Mainstreaming of IDD control in
      policy making, devising State specific action plans to control IDD, strict
      implementation of Food Safety and Standards (FSS) Act, 2006, addressing
      inequities in iodized salt coverage (rural-urban, socio-economic), providing
      iodized salt in Public Distribution System, strengthening monitoring and
      evaluation of IDD programme and ensuring sustainability of IDD control activities
      are essential to achieve sustainable elimination of IDD in India. 

PMID- 24135193
TI  - What should we do if we were wrong and Alzheimer was right?

PMID- 24135194
TI  - Celebrating methodological challenges and changes: reflecting on the emergence
      and importance of the role of qualitative evidence in Cochrane reviews.
AB  - Cochrane systematic reviews have proven to be beneficial for decision making
      processes, both on a practitioner and a policy level, and there are current
      initiatives to extend the types of evidence used by them, including qualitative
      research. In this article we outline the major achievements of the Cochrane
      Qualitative and Implementation Methods Group. Although the Group has encountered
      numerous challenges in dealing with the evolution of qualitative evidence
      synthesis, both outside and within the Cochrane Collaboration, it has
      successfully responded to the challenges posed in terms of incorporating
      qualitative evidence in systematic reviews. The Methods Group will continue to
      advocate for more flexible and inclusive approaches to evidence synthesis in
      order to meet the exciting challenges and opportunities presented by mixed
      methods systematic reviews and reviews of complex interventions. 

PMID- 24135195
TI  - Premature mortality in a Georgian cohort of people with epilepsy.
AB  - Mortality in people with epilepsy has not previously been estimated in Georgia.
      We identified a prevalent cohort of people with epilepsy from a tertiary referral
      centre in Tbilisi, Georgia and attempted to establish survivorship status for
      all. One-way sensitivity analysis estimating mortality rates in those lost to
      follow-up was also used. Of 1952 people, 1250 (64%) were located; 93 (7%) had
      died over a median of 11 years follow up. The main cause specific Proportional
      Mortality Ratios were: underlying diseases (39%) and accidental death (9%). One
      SUDEP was confirmed with a further 4 possible, but the cause of death was unknown
      in 47%. The overall SMR was 1.4, with much higher SMRs (up to 12) in young
      people. The sensitivity analysis suggested an SMR of 3.0. 

PMID- 24135196
TI  - Transient pain developers show increased abdominal muscle activity during
      prolonged sitting.
AB  - BACKGROUND: Sitting is a commonly adopted posture during work and prolonged
      exposures may have detrimental effects. Little attention has been paid to the
      thoracic spine and/or multiple axes of motion during prolonged sitting.
      Accordingly, this study examined three-dimensional motion and muscle activity of
      the trunk during two hours of uninterrupted sitting. METHODS: Ten asymptomatic
      males sat during a simulated office task. Kinematics were analyzed from six
      segments (Neck, Upper-, Mid-, and Lower-thoracic, Lumbar, and Pelvis) and
      electromyography was recorded from eight muscles bilaterally. RESULTS: Four
      participants developed transient pain. These participants showed higher average
      muscle activations in the abdominal muscles. Additionally, the non-pain group
      showed less lateral bend positional change in the mid-thoracic region compared to
      the upper- and lower-thoracic regions. Weak-to-moderate positive correlations
      were also found between rated pain and low back muscle activation. DISCUSSION:
      The results provided further evidence of reduced movement in non-pain developers
      and altered muscle activation patterns in pain developers. Low-level, prolonged
      static contractions could lead to an increased risk of injury; and though the
      increased abdominal activity in the pain developers was not directly associated
      with increased rated pain scores, this could indicate a pre-disposition to, or
      enhancer of, transient pain development.

PMID- 24135197
TI  - Olanzapine-induced hyperglycemia: possible involvement of histaminergic,
      dopaminergic and adrenergic functions in the central nervous system.
AB  - BACKGROUND/AIMS: Atypical antipsychotic drugs such as olanzapine are known to
      induce metabolic disturbance. We have already shown that olanzapine induces
      hepatic glucose production through the activation of hypothalamic adenosine 5'
      monophosphate-activated protein kinase (AMPK). However, it is unclear how
      olanzapine activates hypothalamic AMPK. Since olanzapine is known to antagonize
      several receptors, including histaminergic, muscarinic, serotonergic,
      dopaminergic and adrenergic receptors, we examined the effect of each receptor
      antagonist on blood glucose levels in mice. Moreover, we also investigated
      whether these antagonists activate hypothalamic AMPK. METHODS: Male 6-week-old
      ICR mice were used. Blood glucose levels were determined by the glucose oxidase
      method. AMPK expression was measured by Western blotting. RESULTS: Central
      administration of olanzapine (5-15 nmol i.c.v.) dose-dependently increased blood
      glucose levels in mice, whereas olanzapine did not change blood insulin levels.
      Histamine H1 receptor antagonist chlorpheniramine (1-10 MUg i.c.v.), dopamine D2
      receptor antagonist L-sulpiride (1-10 MUg i.c.v.) and alpha1-adrenoceptor
      antagonist prazosin (0.3-3 MUg i.c.v.) also significantly increased blood glucose
      levels in mice. In contrast, the blood glucose levels were not affected by
      muscarinic M1 receptor antagonist dicyclomine (1-10 MUg i.c.v.) or serotonin 5
      HT2A receptor antagonist M100907 (1-10 ng i.c.v.). Olanzapine-induced
      hyperglycemia was inhibited by the AMPK inhibitor compound C, and AMPK activator
      AICAR (10 ng to 1 MUg i.c.v.) significantly increased blood glucose levels.
      Olanzapine (15 nmol), chlorpheniramine (10 MUg), L-sulpiride (10 MUg) and
      prazosin (3 MUg) significantly increased phosphorylated AMPK in the hypothalamus
      of mice. CONCLUSION: These results suggest that olanzapine activates hypothalamic
      AMPK by antagonizing histamine H1 receptors, dopamine D2 receptors and alpha1
      adrenoceptors, which induces hyperglycemia.

PMID- 24135198
TI  - Correlation between EMG-based co-activation measures and medial and lateral
      compartment loads of the knee during gait.
AB  - BACKGROUND: Inappropriate tibiofemoral joint contact loading during gait is
      thought to contribute to the development of osteoarthritis. Increased co
      activation of agonist/antagonist pair of muscles during gait has commonly been
      observed in pathological populations and it is thought that this results in
      increased articular loading and subsequent risk of disease development. However,
      these hypotheses assume that there is a close relationship between muscle
      electromyography and force production, which is not necessarily the case.
      METHODS: This study investigated the relationship between different
      electromyography-based co-activation measures and articular loading during gait
      using an electromyography-driven model to estimate joint contact loads. FINDINGS:
      The results indicated that significant correlations do exist between selected
      electromyography-based activity measures and articular loading, but these are
      inconsistent and relatively low. However despite this, it was found that it may
      still be possible to use carefully selected measures of muscle activation in
      conjunction with external adduction moment measures to account for up to 50% of
      the variance in medial and lateral compartment loads. INTERPRETATION: The
      inconsistency in correlations between many electromyography-based co-activation
      measures and articular loading still highlights the danger of inferring joint
      contact loads during gait using these measures. These results suggest that some
      form of electromyography-driven modelling is required to estimate joint contact
      loads in the tibiofemoral joint.

PMID- 24135199
TI  - Effect of humeral head rotation on bony glenohumeral stability.
AB  - BACKGROUND: The humeral head and glenoid cavity are not perfectly spherical, nor
      do they have matching radii of curvature. We hypothesized that glenohumeral
      stability is dependent on axial humeral rotation. METHODS: Seven cadaveric
      shoulders were investigated. For each test, the humeral head was translated
      relative to the glenoid in 2 directions (starting from neutral), anterior and
      anteroinferior. Contact forces and lateral humeral displacement were recorded.
      Joint stability was quantified using the stability ratio and energy to
      dislocation. The humerus was set in 60 degrees  of abduction for all tests.
      Testing was performed in neutral rotation and 60 degrees  of external rotation.
      FINDINGS: The force displacement curves differed between rotations. In both
      displacement directions, the peak translational force occurred with less
      displacement in neutral rotation than in external rotation. The stability ratio
      and energy to dislocation in the anteroinferior direction were greater than in
      the anterior direction for both rotation positions. While there were no
      significant differences in the stability ratio or energy to dislocation between
      rotation conditions at complete dislocation, the energy required to move the
      humeral head 10% of the glenoid width was significantly greater with the arm in
      neutral rotation. INTERPRETATION: The energy to dislocation, a new parameter of
      dislocation risk, and the stability ratio, indicate that the glenohumeral joint
      is more stable in the anteroinferior direction than the anterior direction.
      During initial displacement, axial rotation of the humeral head contributes to
      glenohumeral geometrical stability. However, humeral head rotation does not have
      a significant effect when looking at complete dislocation.

PMID- 24135200
TI  - Effect of olanzapine on scopolamine induced deficits in differential
      reinforcement of low rate 72s (DRL-72s) schedule in rats: involvement of the
      serotonergic receptors in restoring the deficits.
AB  - Scopolamine, a non-selective muscarinic receptor antagonist has widespread
      central nervous system effects. Muscarinic receptors located in the central
      nervous system play a vital role in the modulation of impulsivity. The objective
      of the current study was to evaluate the effect of scopolamine on impulsivity
      using differential-reinforcement-of-low-rate 72-s schedule (DRL-72s) and to
      demonstrate the involvement of serotonergic receptors in mediating the effect of
      olanzapine (atypical antipsychotic) on scopolamine induced impulsivity.
      Scopolamine impaired the performance of the rats trained under DRL-72s schedule.
      Olanzapine reversed the deficits induced by scopolamine. We evaluated the effect
      of donepezil (cholinesterase inhibitor), SB-742457 (5-HT6 and 5-HT2a antagonist),
      and haloperidol (typical antipsychotic) in rats challenged with scopolamine in
      the DRL-72s schedule to identify the receptor(s) involved in reversing the
      deficits. SB-742457 partially reversed the deficits, but donepezil and
      haloperidol did not show any effects on the deficits induced by scopolamine.
      Olanzapine and SB-742457 shifted the peak location (PkL) towards longer IRT
      duration, indicating a decrease in motor impulsivity. Modulation of scopolamine
      induced impulsivity by olanzapine could be partly due to its antagonistic action
      at 5-HT2a and 5-HT6 receptors, respectively. Superior effects of olanzapine on
      impulsivity in schizophrenic patients may be mediated through the antagonism of 5
      HT2a and 5-HT6 receptors. 

PMID- 24135201
TI  - Anti-diabetic and anti-inflammatory effect of a novel selective 11beta-HSD1
      inhibitor in the diet-induced obese mice.
AB  - It has been reported that the selective inhibitors of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) have considerable potential for treating type
      2 diabetes mellitus, metabolic syndrome and inflammation. In the present study,
      we investigated the anti-diabetic and anti-inflammatory effects of N-(5
      carbamoyladamantan-2-yl)-3-((2-fluorophenyl) sulfonyl)thiazolidine-2-carboxamide
      (KR-67105), a novel 11beta-HSD1 inhibitor, in diabetic mice model and
      preadipocyte model. KR-67105 concentration dependently inhibited 11beta-HSD1
      activity in human and mouse 11beta-HSD1 overexpressing cells and mouse 3T3-L1
      adipocytes. Furthermore, KR-67105 concentration-dependently inhibited 11beta-HSD1
      activity in the ex vivo assay of C57BL/6 mice. In the study with diet-induced
      obese (DIO) mice, the administration of KR-67105 (100mg/kg/day, orally for 28
      days) improved the glucose tolerance and insulin sensitivity as determined by the
      oral glucose tolerance test and the insulin tolerance test. Anti-diabetic effect
      by KR-67105 was associated with the suppression of diabetic related genes
      expression in liver and fat. Furthermore, KR-67105 suppressed 11beta-HSD1
      activity in liver and fat of diabetic mice, but showed no effect on adrenal grand
      weight/body weight ratio and plasma corticosterone concentration in diabetic
      mice. In 3T3-L1 preadipocytes, cortisone induced the mRNA of inflammatory
      cytokines and 11beta-HSD1 and reactive oxygen species formation. This effect was
      abolished by co-incubation with KR-67105 in a concentration-dependent manner.
      Moreover, KR-67105 attenuated cortisone induced iNOS expression and
      phosphorylation of NF-kappaB p65, p38 MAPK, and ERK1/2 in preadipocytes. Taken
      together, it is concluded that a selective 11beta-HSD1 inhibitor, KR-67105, may
      provide a new therapeutic window in the prevention and treatment of type 2
      diabetes with chronic inflammation without toxicity. 

PMID- 24135202
TI  - AQP4 KO exacerbating renal dysfunction is mediated by endoplasmic reticulum
      stress and p66Shc and is attenuated by apocynin and endothelin antagonist
      CPU0213.
AB  - Aquaporin 4 (AQP4) is essential in normal kidney. We hypothesized that AQP4
      knockout (KO) may exacerbate pro-inflammatory factors in the stress induced renal
      insufficiency. Mechanisms underlying are likely due to activating renal oxidative
      stress adaptor p66Shc and endoplasmic reticulum (ER) stress that could be
      mediated by endothelin (ET)-NADPH oxidase (NOX) pathway. AQP4 KO and wild type
      (WT) mice were randomly divided into 4 groups: control, isoproterenol (1mg/kg,
      s.c., 5d), and interventions in the last 3 days with either apocynin (NADPH
      oxidase inhibitor, 100mg/kg, p.o.) or CPU0213 (a dual endothelin receptor
      antagonist 200mg/kg, p.o.). In addition, HK2 cells were cultured in 4 groups:
      control, isoproterenol (10(-6)M), intervened with apocynin (10(-6)M) or CPU0213
      (10(-6)M). In AQP4 KO mice elevated creatinine levels were further increased by
      isoproterenol compared to AQP4 KO alone. In RT-PCR, western blot and
      immunohistochemical assay p66Shc and PERK were significantly increased in the
      kidney of AQP4 KO mice, associated with pro-inflammatory factors CX40, CX43, MMP
      9 and ETA compared to the WT mice. Expression of AQP4 was escalated in
      isoproterenol incubated HK2 cells, and the enhanced protein of PERK and p
      PERK/PERK, and p66shc in vivo and in vitro were significantly attenuated by
      either apocynin or CPU0213. In conclusion, AQP4 KO deteriorates renal dysfunction
      due to exacerbating ER stress and p66Shc in the kidney. Either endothelin
      antagonism or NADPH oxidase blockade partly relieves renal dysfunction through
      suppressing abnormal biomarkers by APQ4 KO and isoproterenol in the kidney. 

PMID- 24135203
TI  - On the centrality of disturbance rejection in automatic control.
AB  - In this paper, it is shown that the problem of automatic control is, in essence,
      that of disturbance rejection, with the notion of disturbance generalized to
      symbolize the uncertainties, both internal and external to the plant. A novel,
      unifying concept of disturbance rejector is proposed to compliment the
      traditional notion of controller. The new controller-rejector pair is shown to be
      a powerful organizing principle in the realm of automatic control, leading to a
      Copernican moment where the model-centric design philosophy is replaced by the
      one that is control-centric in the following sense: the controller is designed
      for a canonical model and is fixed; the difference between the plant and the
      canonical model is deemed as disturbance and rejected. 

PMID- 24135204
TI  - Brain banking: more effective strategies needed.

PMID- 24135206
TI  - Ian Gilron: pain killer.

PMID- 24135208
TI  - Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and
      treatment.
AB  - Intracranial atherosclerosis is one of the most common causes of stroke worldwide
      and is associated with a high risk of recurrent stroke. New therapeutic
      approaches to treat this high-risk disease include dual antiplatelet treatment,
      intensive management of risk factors, and endovascular therapy. Early data from
      randomised trials indicate that aggressive medical therapy is better than
      stenting for prevention of recurrent stroke in high-risk patients with
      atherosclerotic stenosis of a major intracranial artery. Nevertheless, there are
      subgroups of patients who remain at high risk of stroke despite aggressive
      medical therapy. Further research is needed to identify these high-risk subgroups
      and to develop more effective treatments. Non-invasive vascular imaging methods
      that could be used to identify high-risk patients include fractional flow on
      magnetic resonance angiography (MRA), quantitative MRA, and high-resolution MRI
      of the atherosclerotic plaque. Alternative therapies to consider for future
      clinical trials include angioplasty alone, indirect surgical bypass procedures,
      ischaemic preconditioning, and new anticoagulants (direct thrombin or Xa
      inhibitors). 

PMID- 24135209
TI  - Outcomes of isolated basilar skull fracture: readmission, meningitis, and
      cerebrospinal fluid leak.
AB  - OBJECTIVE: To determine rates of cerebrospinal fluid (CSF) leak, meningitis, and
      readmission in pediatric and adult patients with isolated basilar skull fracture.
      STUDY DESIGN: Cross-sectional analysis of a statewide database. SUBJECTS:
      Patients with isolated basilar skull fracture (1995-2010). METHODS: Patients were
      identified within the California Office of Statewide Health Planning and
      Development database using ICD-9 diagnosis codes. RESULTS: A total of 3563
      pediatric and 10,761 adult patients met inclusion criteria. In-hospital rates of
      meningitis (0.48% and 0.64%, P = .3360) and CSF leak (2.33% and 1.75%, P = .0270)
      were similar among children and adults, respectively. Rates of 90-day meningitis
      (0.17% and 0.37%, P = .0714) and CSF leak (0.40% and 0.40%, P = .9823) were also
      similar. Thirty-day readmission was 4.6% for children compared with 12.4% for
      adults (P < .001). For both pediatric and adult patients, extra-axial hematoma
      (odds ratio [OR] [confidence interval {CI}] 1.65 [1.05-2.59] and 1.61 [1.34
      1.95]) and comorbidities (OR [CI] 2.19 [1.11-4.34] and 1.28 [1.04-1.59]) were
      associated with significant increases in 30-day readmission. Loss of
      consciousness greater than 1 hour (OR, 3.05; 95% CI, 1.53-6.08) and CSF leak (OR,
      3.28; 95% CI, 1.41-7.64) increased the likelihood of pediatric readmissions. Lack
      of insurance (OR, 0.67; 95% CI, 0.50-0.90) and female gender (OR 0.83; 95% CI,
      0.70-0.99) reduced the likelihood of adult readmission. CONCLUSION: Meningitis
      and CSF leak following isolated basilar skull fractures are uncommon. Readmission
      within 30 days was more common in adults than in children. CSF leak, hematoma,
      and prolonged loss of consciousness increased the likelihood of readmission in
      children. Intracranial injury, male gender, having insurance, and comorbidities
      increased the likelihood of readmission in adults.

PMID- 24135211
TI  - Incidentally detected right pulmonary artery agenesis with right coronary artery
      collateralization.
AB  - Unilateral pulmonary artery agenesis (UPAA) with pulmonary hypoplasia is a rare
      congenital anomaly. We describe a 71-year old male who was incidentally diagnosed
      with the right UPAA and a hypoplastic right lung supplied by collateralized right
      coronary. 

PMID- 24135210
TI  - Elevating endocannabinoid levels: pharmacological strategies and potential
      therapeutic applications.
AB  - The endocannabinoid system consists of cannabinoid CB1 and CB2 receptors, of
      endogenous agonists for these receptors known as 'endocannabinoids', and of
      processes responsible for endocannabinoid biosynthesis, cellular uptake and
      metabolism. There is strong evidence first, that this system up-regulates in
      certain disorders as indicated by an increased release of endocannabinoids onto
      their receptors and/or by increases in the expression levels or coupling
      efficiency of these receptors, and second, that this up-regulation often appears
      to reduce or abolish unwanted effects of these disorders or to slow their
      progression. This discovery has raised the possibility of developing a medicine
      that enhances up-regulation of the endocannabinoid system associated with these
      disorders by inhibiting the cellular uptake or intracellular metabolism of an
      endocannabinoid following its 'autoprotective' endogenous release. For inhibition
      of endocannabinoid metabolism, research has focused particularly on two highly
      investigated endocannabinoids, anandamide and 2-arachidonoyl glycerol, and hence
      on inhibitors of the main anandamide-metabolising enzyme, fatty acid amide
      hydrolase (FAAH), and of the main 2-arachidonoyl glycerol-metabolising enzyme,
      monoacylglycerol (MAG) lipase. The resulting data have provided strong
      preclinical evidence that selective FAAH and MAG lipase inhibitors would
      ameliorate the unwanted effects of several disorders, when administered alone or
      with a cyclooxygenase inhibitor, and that the benefit-to-risk ratio of a FAAH
      inhibitor would exceed that of a MAG lipase inhibitor or dual inhibitor of FAAH
      and MAG lipase. Promising preclinical data have also been obtained with
      inhibitors of endocannabinoid cellular uptake. There is now an urgent need for
      clinical research with these enzyme and uptake inhibitors. 

PMID- 24135212
TI  - Impact of an open-chest extracorporeal membrane oxygenation model for in situ
      simulated team training: a pilot study.
AB  - OBJECTIVES: To develop an affordable realistic open-chest extracorporeal membrane
      oxygenation (ECMO) model for embedded in situ interprofessional crisis resource
      management training in emergency management of a post-cardiac surgery child.
      METHODS: An innovative attachment to a high-fidelity mannequin (Laerdal Simbaby)
      was used to enable a cardiac tamponade/ECMO standstill scenario. Two saline bags
      with blood dye were placed over the mannequin's chest. A 'heart' bag with venous
      and arterial outlets was connected to the corresponding tubes of the ECMO
      circuit. The bag was divided into arterial and venous parts by loosely wrapping
      silicon tubing around its centre. A 'pericardial' bag was placed above it. Both
      were then covered by a chest skin that had a sutured silicone membrane window.
      False blood injected into the 'pericardial' bag caused expansion leading to (i)
      bulging of silastic membrane, simulating tamponade, and (ii) compression of
      tubing around the 'heart' bag, creating negative venous pressures and cessation
      of ECMO flow. In situ Simulation Paediatric Resuscitation Team Training (SPRinT)
      was performed on paediatric intensive care unit; the course included a formal
      team training/scenario of an open-chest ECMO child with acute cardiac tamponade
      due to blocked chest drains/debriefing by trained facilitators. RESULTS: Cardiac
      tamponade was reproducible, and ECMO flow/circuit pressure changes were effective
      and appropriate. There were eight participants: one cardiac surgeon, two
      intensivists, one cardiologist, one perfusionist and three nurses. Five of the
      eight reported the realism of the model and 6/8 the realism of the clinical
      scenario as highly effective. Eight of eight reported a highly effective impact
      on (i) their practice and (ii) teamwork. Six of eight reported a highly effective
      impact on communication skills and increased confidence in attending future real
      events. CONCLUSIONS: Innovative adaptation of a high-fidelity mannequin for open
      chest ECMO simulation can achieve a realistic and reproducible training model.
      The impact on interprofessional team training is promising but needs to be
      validated further.

PMID- 24135213
TI  - Rethinking the dose-response relationship between usage and outcome in an online
      intervention for depression: randomized controlled trial.
AB  - BACKGROUND: There is now substantial evidence that Web-based interventions can be
      effective at changing behavior and successfully treating psychological disorders.
      However, interest in the impact of usage on intervention outcomes has only been
      developed recently. To date, persistence with or completion of the intervention
      has been the most commonly reported metric of use, but this does not adequately
      describe user behavior online. Analysis of alternative measures of usage and
      their relationship to outcome may help to understand how much of the intervention
      users may need to obtain a clinically significant benefit from the program.
      OBJECTIVE: The objective of this study was to determine which usage metrics, if
      any, are associated with outcome in an online depression treatment trial.
      METHODS: Cardiovascular Risk E-couch Depression Outcome (CREDO) is a randomized
      controlled trial evaluating an unguided Web-based program (E-couch) based on
      cognitive behavioral therapy and interpersonal therapy for people with depression
      and cardiovascular disease. In all, 280 participants in the active arm of the
      trial commenced the program, delivered in 12 modules containing pages of text and
      activities. Usage data (eg, number of log-ins, modules completed, time spent
      online, and activities completed) were captured automatically by the program
      interface. We estimated the association of these and composite metrics with the
      outcome of a clinically significant improvement in depression score on the
      Patient Health Questionnaire (PHQ-9) of >= 5 points. RESULTS: In all, 214/280
      (76.4%) participants provided outcome data at the end of the 12-week period and
      were included in the analysis. Of these, 94 (43.9%) participants obtained
      clinically significant improvement. Participants logged into the program an
      average of 18.7 times (SD 8.3) with most (62.1%, 133/214) completing all 12
      modules. Average time spent online per log-in was 17.3 minutes (SD 10.5).
      Participants completed an average of 9 of 18 activities available within the
      program. In a multivariate regression model, only the number of activities
      completed per log-in was associated with a clinically significant outcome (OR
      2.82, 95% CI 1.05-7.59). The final model predicted 7.4% of variance in outcome.
      Curve estimates indicated that significant logarithmic (P=.009) and linear
      (P=.002) relationships existed between activities completed per log-in and
      clinically significant change. CONCLUSIONS: Only one objective measure of usage
      was independently associated with better outcome of a Web-based intervention of
      known effectiveness. The 4 usage metrics retained in the final step of the
      regression accounted for little outcome variance. Medium level users appeared to
      have little additional benefit compared to low users indicating that assumptions
      of a linear relationship between use and outcome may be too simplistic and
      further models and variables need to be explored to adequately understand the
      relationship.

PMID- 24135214
TI  - Extrinsic skin ageing symptoms in seafarers subject to high work-related exposure
      to UV radiation.
AB  - OBJECTIVES: As outdoor workers, seafarers have high levels of work-related
      exposure to UV radiation. Considering the various ethnic shipboard crews, this
      study aimed to assess the prevalence of UV induced skin ageing symptoms among
      seafarers and their attitude towards sunlight exposure. METHODS: One
      dermatologist examined 514 seafarers and documented the presence of 11 extrinsic
      skin ageing symptoms. Based on a questionnaire, the seafarers' attitudes and sun
      protection were evaluated. RESULTS: On average, 4 extrinsic skin ageing symptoms
      were found among the seafarers without significant differences between ethnic
      groups. Teleangiectasis (n = 381), coarse wrinkles (n = 315) and lentigines
      solares (n = 228) were the most frequently observed extrinsic symptoms. In the
      multivariate analysis, the parameters current smoking (OR 1.52 (1.01-2.27)),
      shipboard rank (deck personnel, galley staff vs. engine room personnel; (OR 1.40
      (1.01-1.94)), and age (OR 1.07 (1.05-1.10)) were significantly associated with
      developing skin ageing symptoms. Only half of the seafarers examined were aware
      of their elevated risk of photodamage due to their high UV exposure at sea. More
      non-Caucasian than Caucasian seafarers perceived tanned skin as rather positive
      (78.0% vs. 52.4%; p = 0.002); however, more Caucasian than non-Caucasian
      seafarers enjoyed intensive sunbathing (17.0% vs. 14.0%). Furthermore, 55.7% of
      the seafarers (significantly more often Caucasians) used sunscreens during
      sunlight exposure at sea. CONCLUSIONS: The various ethnic groups examined
      differed in their attitude and behaviour towards shipboard sun exposure.
      Education of shipboard crews is required about possible severe health effects due
      to sun exposure at sea.

PMID- 24135215
TI  - Priapism in children: a comprehensive review and clinical guideline.
AB  - OBJECTIVE: We review the English literature between 1980 and 2013 and summarize
      the clinical classification, aetiology, physiology, and pathophysiology of
      paediatric priapism. We propose a clinical guideline for the management of
      priapism in children. PATIENTS: Male patients aged <= 18 years. RESULTS:
      Priapism, a prolonged penile erection lasting >4 h, is a rare condition in
      childhood. There are 3 widely accepted types of priapism: 1) ischaemic priapism,
      the commonest type seen in children; 2) stuttering priapism, recurrent, self
      limiting prolonged erections; and 3) non-ischaemic priapism, rare in children,
      usually due to trauma. Neonatal priapism has also been described. Ischaemic
      priapism is a urological emergency causing fibrosis of the corpora cavernosa,
      subsequent erectile dysfunction and penile disfigurement. The commonest causes of
      priapism in children are sickle cell disease (65%), leukaemia (10%), trauma
      (10%), idiopathic (10%), and pharmacologically induced (5%). CONCLUSIONS:
      Priapism in children must be assessed urgently. Rapid resolution of ischaemic
      priapism prevents permanent cavernosal structural damage and is associated with
      improved prognosis for potency later in life. Stuttering priapism requires
      careful counselling for episodic management. Chronic prophylaxis may be obtained
      using alpha-adrenergic sympathomimetics, phosphodiesterase type 5 inhibitors and,
      in sickle cell disease, hydroxyurea. Non-ischaemic and neonatal priapism may
      generally be treated less urgently.

PMID- 24135216
TI  - Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein
      2 in Plasmodium falciparum isolates from children in South of Benin.
AB  - The aim of this study was to determine the genetic diversity of Plasmodium
      falciparum by analyzing the polymorphism of the msp-1 and msp-2 genes and the
      multiplicity of infection in children with uncomplicated malaria in southern
      Benin. Blood samples of children with fever or history of fever with thick smear
      positive P. falciparum were collected on filter paper. After extraction of DNA by
      Chelex(r), the samples underwent nested PCR. 93 isolates from children were
      genotyped. For the msp-1 gene, the K1 and R033 sequences were the most
      represented in the study population with 85.2% and 83% prevalence, respectively.
      Regarding the msp-2 gene, the FC27 family was more highly represented with 99%
      prevalence against 81.5% for 3D7. Mixed infections accounted for 80.4% of the
      samples. Twenty-five alleles were identified for msp-1 and 28 for msp-2. Fourteen
      and ten alleles belonged to the K1 (100-500 bp) and MAD20 (100-500 bp) families,
      respectively. The RO33 sequence did not show any polymorphism, with only one
      variant (160 bp) detected. The msp-2 gene was present as 16 FC27 family fragments
      (250-800 bp) and 12 of the 3D7 family (350-700 bp). The multiplicity of infection
      was estimated at 3.8 for msp-1 and 3.9 for msp-2 with 77 (87.5%) and 84 (91.3%)
      samples harboring more than one parasite genotype for msp-1 and msp-2,
      respectively. The multiplicity of infection (MOI) was influenced neither by age
      nor by parasite density. This study shows a significant diversity of P.
      falciparum in southern Benin with an MOI unaffected by age or by parasite
      density.

PMID- 24135217
TI  - Vitamin D deficiency: consequence or cause of CKD?

PMID- 24135219
TI  - Protective effect of orexin-A on 6-hydroxydopamine-induced neurotoxicity in SH
      SY5Y human dopaminergic neuroblastoma cells.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease characterized
      by progressive and selective death of midbrain dopaminergic neurons.
      Pharmacologic treatment of PD can be divided into symptomatic and neuroprotective
      therapies. Orexin-A (hypocretin-1) is a hypothalamic peptide that exerts its
      biological effects by stimulation of two specific, membrane-bound orexin
      receptors. Recent studies have shown that orexin-A has a protective role during
      neuronal damage. Here, we investigated the effects of orexin-A on 6-OHDA-induced
      neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of
      Parkinson's disease. Cell damage was induced by 150MUM 6-OHDA and the cells
      viability was examined by MTT assay. Intracellular reactive oxygen species (ROS)
      was determined by fluorescence spectrophotometry method. Immunoblotting and DNA
      analysis were also employed to determine the levels of biochemical markers of
      apoptosis in the cells. The data showed that 6-OHDA could decrease the viability
      of the cells. In addition, intracellular ROS, activated caspase 3, Bax/Bcl-2
      ratio, cytochrome c as well as DNA fragmentation were significantly increased in
      6-OHDA-treated cells. Pretreatment of cells with orexin-A (80pM) elicited
      protective effect and reduced biochemical markers of cell death. The results
      suggest that orexin-A has protective effects against 6-OHDA-induced neurotoxicity
      and its protective effects are accompanied by its antioxidant and anti-apoptotic
      properties and contribute to our knowledge of the pharmacology of orexin-A. 

PMID- 24135220
TI  - How complementary are epibenthic assemblages in artificial and nearby natural
      rocky reefs?
AB  - The present study analyses the composition, structure and trophic function of
      epibenthic assemblages in two artificial reefs (ARs) 16 years after deployment
      and in nearby natural reefs (NRs), aiming at providing insights on the
      complementarity between both habitats. Current findings suggest that after 16
      years the ARs (concrete blocks), located in southern Portugal, do not act as
      surrogates for NRs, as epibenthic assemblages differed between reef types in
      composition, structure and trophic function. NRs showed higher diversity and
      complementarity (i.e. beta-diversity) than ARs, evidencing higher redundancy.
      Higher heterogeneity within NRs was also evidenced by the multi-dimensional
      scaling analysis based on abundance, biomass and trophic composition. NRs
      presented higher abundance of molluscs and biomass of sponges, resulting in
      differences in the trophic function: suspension-feeding dominated the NRs, while
      within ARs there was an ascendency of carnivory. Although not acting as
      surrogates for NRs and provided that no adverse effects (e.g. establishment of
      non-native species) were detected, ARs may have a significant contribution for
      the increase of regional diversity, as evidenced by the highest complementarity
      levels observed between assemblages in both reefs. 

PMID- 24135218
TI  - 25 (OH) vitamin D levels and renal disease progression in patients with type 2
      diabetic nephropathy and blockade of the renin-angiotensin system.
AB  - BACKGROUND AND OBJECTIVES: Experimental studies show that 25 (OH) vitamin D is a
      suppressor of renin biosynthesis and that vitamin D deficiency has been
      associated with CKD progression. Patients with type II diabetes and CKD have an
      exceptionally high rate of severe 25 (OH) vitamin D deficiency; however, it is
      not known whether this deficiency is a risk factor for progression of diabetic
      nephropathy. This study aimed to investigate whether there is an association of
      25 (OH) vitamin D deficiency with disease progression in type II diabetic
      nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 25 (OH) vitamin D
      levels were measured at baseline and 4 and 12 months in 103 patients included in
      a multicenter randomized controlled trial to compare the efficacy of combining an
      angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker with
      the efficacy of each drug in monotherapy to slow progression of established
      diabetic nephropathy during 2006-2011. The primary composite endpoint was a >50%
      increase in baseline serum creatinine, ESRD, or death. All study participants
      were included in the analysis. RESULTS: Fifty-three patients (51.5%) had 25 (OH)
      vitamin D deficiency (<15 ng/ml). After a median follow-up of 32 months, the
      endpoint was reached by 23 patients with deficiency (43.4%) and 8 patients
      without (16%). Multivariate Cox regression analysis adjusted for urinary
      protein/creatinine ratio, estimated GFR, and baseline aldosterone showed that 25
      (OH) vitamin D deficiency was associated with the primary endpoint (hazard ratio,
      2.88; 95% confidence interval, 1.84 to 7.67; P=0.04). CONCLUSIONS: These results
      show that 25 (OH) vitamin D deficiency is independently associated with a higher
      risk of the composite outcome in patients with type II diabetic nephropathy.

PMID- 24135222
TI  - Differential effects upon brain and serum BDNF levels in rats as response to
      continuous and intermittent administration strategies of two second generation
      antipsychotics.

PMID- 24135221
TI  - Multivariate pattern analysis of FMRI in breast cancer survivors and healthy
      women.
AB  - Advances in breast cancer (BC) treatments have resulted in significantly improved
      survival rates. However, BC chemotherapy is often associated with several side
      effects including cognitive dysfunction. We applied multivariate pattern analysis
      (MVPA) to functional magnetic resonance imaging (fMRI) to find a brain
      connectivity pattern that accurately and automatically distinguishes chemotherapy
      treated (C+) from non-chemotherapy treated (C-) BC females and healthy female
      controls (HC). Twenty-seven C+, 29 C-, and 30 HC underwent fMRI during an
      executive-prefrontal task (Go/Nogo). The pattern of functional connectivity
      associated with this task discriminated with significant accuracy between C+ and
      HC groups (72%, p = .006) and between C+ and C- groups (71%, p = .012). However,
      the accuracy of discrimination between C- and HC was not significant (51%, p =
      .46). Compared with HC, behavioral performance of the C+ and C- groups during the
      task was intact. However, the C+ group demonstrated altered functional
      connectivity in the right frontoparietal and left supplementary motor area
      networks compared to HC, and in the right middle frontal and left superior
      frontal gyri networks, compared to C-. Our results provide further evidence that
      executive function performance may be preserved in some chemotherapy-treated BC
      survivors through recruitment of additional neural connections.

PMID- 24135223
TI  - Facial emotion recognition in schizophrenia: a comparison with siblings and
      control subjects.

PMID- 24135224
TI  - Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is an infection often
      occurring in neutropenic patients and has high mortality rates. In recent years,
      it has been reported that the incidence of IPA has also increased in patients
      with chronic obstructive pulmonary disease (COPD). The purpose of this study is
      to investigate the clinical and demographic characteristics and treatment
      responses of IPA in patients with COPD. METHODS: Seventy-one patients with a
      positive culture of Aspergillus from lower respiratory tract samples were
      examined retrospectively. Eleven (15.4%) of these patients, affected with grade 3
      or 4 COPD, had IPA. RESULTS: Aspergillus hyphae were detected in lung biopsy in
      three (27.3%) out of 11 patients and defined as proven IPA; a pathological sample
      was not taken in the other eight (72.7%) patients, and these were defined as
      probable IPA. Aspergillus isolates were identified as six cases of
      Aspergillusfumigatus and three of Aspergillusniger in nine patients, while two
      isolates were not identified at species level. While five patients required
      intensive care unit admission, four of them received mechanical ventilation. The
      most common finding on chest X-ray and computed tomography (CT) (respectively
      63.6%, 72.7%) was infiltration. Amphotericin B was the initial drug of choice in
      all patients and five patients were discharged with oral voriconazole after
      amphotericin B therapy. Six patients (54.5%) died before treatment was completed.
      CONCLUSIONS: IPA should be taken into account in the differential diagnosis
      particularly in patients with severe and very severe COPD presenting with dyspnea
      exacerbation, poor clinical status, and a new pulmonary infiltrate under
      treatment with broad-spectrum antibiotics and steroids.

PMID- 24135225
TI  - Down-regulation of RE-1 silencing transcription factor (REST) in advanced
      prostate cancer by hypoxia-induced miR-106b~25.
AB  - Clinically aggressive prostate cancer (PCa) is linked to androgen resistance,
      metastasis, and expression of neuroendocrine markers. To understand mechanism(s)
      of neuroendocrine differentiation (NED) of PCa epithelia, we compared neuronal
      differentiation occurring during embryogenesis, in primary cultures of neural
      crest (NC) cells, and NED in PCa cell lines (LNCaP and PC3). We demonstrate,
      hypoxia promotes neuronal and neuroendocrine differentiation of NC cells and PCa
      cells, respectively, by inducing the miR-106 b~25 cluster. In turn, miR-106b~25
      comprised of miR-106b, miR-93 and miR-25, down-regulates the transcriptional
      repressor REST, which represses neuron-specific protein-coding and miRNA genes.
      In prostate tumors of high Gleason score (>= 8), an inverse trend was observed
      between REST and miR-106b~25 induction. Employing miRNA PCR arrays, we identified
      miRNAs up-regulated by hypoxia in LNCaP cells and REST-knockdown in NC cells.
      Significantly, a subset of miRNAs (miR-9, miR-25, miR-30d and miR302b) is up
      regulated in high Gleason score (>= 8) PCa, suggesting a mechanism by which NED
      contributes to PCa malignancy. We propose that loss of REST and induction of this
      set of microRNAs can serve as potential novel clinical markers of advanced PCa.

PMID- 24135226
TI  - Sculpting the nucleus with dynamic microtubules.
AB  - How nuclear morphology is regulated during development and disease remains poorly
      understood. In this issue of Developmental Cell, using a pronuclear assembly
      assay, Xue et al. (2013) demonstrate that Dppa2, a chromatin-bound microtubule
      regulator, controls both the morphology and function of the pronucleus by fine
      tuning microtubule dynamics. 

PMID- 24135227
TI  - The birth of the barrels.
AB  - Refinement of sensory maps follows a highly reproducible tempo dictated largely
      by peripheral sensory receptors and neural activity. In this issue of
      Developmental Cell, Toda et al. (2013) add a new twist by showing that the timing
      of birth plays a decisive role in setting the clock for pattern emergence. 

PMID- 24135228
TI  - WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP
      like progenitors within the adrenal gland.
AB  - Adrenal glands and gonads share a common primordium (AGP), but the molecular
      events driving differentiation are poorly understood. Here we demonstrate that
      the Wilms tumor suppressor WT1 is a key factor defining AGP identity by
      inhibiting the steroidogenic differentiation process. Indeed, ectopic expression
      of WT1 precludes differentiation into adrenocortical steroidogenic cells by
      locking them into a progenitor state. Chromatin immunoprecipitation experiments
      identify Tcf21 and Gli1 as direct targets of WT1. Moreover, cell lineage tracing
      analyses identify a long-living progenitor population within the adrenal gland,
      characterized by the expression of WT1, GATA4, GLI1, and TCF21, that can generate
      steroidogenic cells in vivo. Strikingly, gonadectomy dramatically activates these
      WT1(+) cells and leads to their differentiation into gonadal steroidogenic
      tissue. Thus, our data describe a mechanism of response to organ loss by
      recreating hormone-producing cells at a heterotopic site. 

PMID- 24135230
TI  - Birth regulates the initiation of sensory map formation through serotonin
      signaling.
AB  - Although the mechanisms underlying the spatial pattern formation of sensory maps
      have been extensively investigated, those triggering sensory map formation during
      development are largely unknown. Here we show that the birth of pups
      instructively and selectively regulates the initiation of barrel formation in the
      somatosensory cortex by reducing serotonin concentration. We found that preterm
      birth accelerated barrel formation, whereas it did not affect either barreloid
      formation or barrel structural plasticity. We also found that serotonin was
      selectively reduced soon after birth and that the reduction of serotonin was
      triggered by birth. The reduction of serotonin was necessary and sufficient for
      the effect of birth on barrel formation. Interestingly, the regulatory mechanisms
      described here were also found to regulate eye-specific segregation in the visual
      system, suggesting that they are utilized in various brain regions. Our results
      shed light on roles of birth and serotonin in sensory map formation. 

PMID- 24135229
TI  - Local Dkk1 crosstalk from breeding ornaments impedes regeneration of injured male
      zebrafish fins.
AB  - Precise spatiotemporal regulation of signaling activators and inhibitors can help
      limit developmental crosstalk between neighboring tissues during morphogenesis,
      homeostasis, and regeneration. Here, we find that the secreted Wnt inhibitor
      Dkk1b is abundantly produced by dense regions of androgen-regulated epidermal
      tubercles (ETs) on the surfaces of adult male zebrafish pectoral fins. High-speed
      videos and amputation experiments reveal that pectoral fins and their ETs are
      used for male spawning. Formation and vigorous turnover of ETs involve Dkk1b
      induction and maintenance, whereas Dkk1b is typically restricted from the
      regeneration blastema after an amputation injury. When amputation occurs through
      a region containing ETs, a Dkk1b-enriched wound epidermis forms and blastema
      formation is disrupted, compromising regeneration. Thus, homeostatic signaling by
      key breeding ornaments can interfere with injury-activated tissue regeneration.
      Our findings help explain sexually dimorphic fin regeneration in zebrafish and
      have implications for how regenerative potential might decline as development
      progresses or during species evolution. 

PMID- 24135231
TI  - Nonautonomous movement of chromosomes in mitosis.
AB  - Kinetochores are the central force-generating machines that move chromosomes
      during cell division. It is generally assumed that kinetochores move in an
      autonomous manner. However, we reveal here that movements of neighboring sister
      kinetochore pairs in metaphase are correlated in a distance-dependent manner.
      This correlation increases in the absence of kinetochore oscillations or stable
      end-on attachments. This suggests that periodic movements of bioriented
      chromosomes limit the correlated motion of nonsisters. Computer simulations show
      that these correlated movements can occur when elastic crosslinks are placed
      between the K-fibers of oscillating kinetochores. Strikingly, inhibition of the
      microtubule crosslinking motor kinesin-5 Eg5 leads to an increase in nonsister
      correlation and impairs periodic oscillations. These phenotypes are partially
      rescued by codepletion of the kinesin-12 Kif15, demonstrating a function for
      kinesin-5 and kinesin-12 motors in driving chromosome movements, possibly as part
      of a crosslinking structure that correlates the movements of nonsister
      kinetochores. 

PMID- 24135232
TI  - A molecular blueprint at the apical surface establishes planar asymmetry in
      cochlear hair cells.
AB  - Sound perception relies on the planar polarization of the mechanosensory hair
      cell apex, which develops a V-shaped stereocilia bundle pointing toward an
      eccentric kinocilium. It remains unknown how intrinsically asymmetric bundles
      arise and are concomitantly oriented in the tissue. We report here that mInsc,
      LGN, and Galphai proteins, which classically regulate mitotic spindle
      orientation, are polarized in a lateral microvilli-free region, or "bare zone,"
      at the apical hair cell surface. By creating and extending the bare zone, these
      proteins trigger a relocalization of the eccentric kinocilium midway toward the
      cell center. aPKC is restrained medially by mInsc/LGN/Galphai, resulting in
      compartmentalization of the apical surface that imparts the V-shaped distribution
      of stereocilia and brings the asymmetric bundle in register with the relocalized
      kinocilium. Galphai is additionally required for lateral orientation of cochlear
      hair cells, providing a possible mechanism to couple the emergence of asymmetric
      stereocilia bundles with planar cell polarity. 

PMID- 24135233
TI  - Cell surface and cell outline imaging in plant tissues using the backscattered
      electron detector in a variable pressure scanning electron microscope.
AB  - BACKGROUND: Scanning electron microscopy (SEM) has been used for high-resolution
      imaging of plant cell surfaces for many decades. Most SEM imaging employs the
      secondary electron detector under high vacuum to provide pseudo-3D images of
      plant organs and especially of surface structures such as trichomes and stomatal
      guard cells; these samples generally have to be metal-coated to avoid charging
      artefacts. Variable pressure-SEM allows examination of uncoated tissues, and
      provides a flexible range of options for imaging, either with a secondary
      electron detector or backscattered electron detector. In one application, we used
      the backscattered electron detector under low vacuum conditions to collect images
      of uncoated barley leaf tissue followed by simple quantification of cell areas.
      RESULTS: Here, we outline methods for backscattered electron imaging of a variety
      of plant tissues with particular focus on collecting images for quantification of
      cell size and shape. We demonstrate the advantages of this technique over other
      methods to obtain high contrast cell outlines, and define a set of parameters for
      imaging Arabidopsis thaliana leaf epidermal cells together with a simple image
      analysis protocol. We also show how to vary parameters such as accelerating
      voltage and chamber pressure to optimise imaging in a range of other plant
      tissues. CONCLUSIONS: Backscattered electron imaging of uncoated plant tissue
      allows acquisition of images showing details of plant morphology together with
      images of high contrast cell outlines suitable for semi-automated image analysis.
      The method is easily adaptable to many types of tissue and suitable for any
      laboratory with standard SEM preparation equipment and a variable-pressure-SEM or
      tabletop SEM.

PMID- 24135234
TI  - Thrombolytic therapy is an only determinant factor for stroke evolution in large
      anterior choroidal artery infarcts.
AB  - BACKGROUND: Large anterior choroidal artery (AChA) infarcts are frequently
      associated with stroke evolution. This study aimed to investigate the major
      determinants for stroke evolution in patients with large AChA infarcts. METHODS:
      We studied 118 consecutive adult patients with acute large AChA infarcts. The
      diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal
      magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted
      imaging within typical AChA vascular regions. Stroke evolution was defined as
      neurologic deterioration with an increase in National Institutes of Health Stroke
      Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function
      by at least 2 in 7 days after stroke onset. RESULTS: Forty-seven (39.8%) patients
      developed stroke evolution. Thrombolytic therapy was inversely associated with
      the occurrence of stroke evolution (P = .004). Using multivariate analysis,
      thrombolytic therapy was the only protective determinant for stroke evolution
      (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with
      large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term
      functional outcome than those not receiving thrombolytic therapy (adjusted odds
      ratio, .11; 95% confidence interval, .02-.75). CONCLUSIONS: Thrombolytic therapy
      is an only determinant factor for stroke evolution in large AChA infarcts, which
      reduced the risk of stroke evolution and improved functional outcome.

PMID- 24135235
TI  - Cilostazol inhibits platelet-endothelial cell interaction in murine microvessels
      after transient bilateral common carotid artery occlusion.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of
      cilostazol on platelet behavior (rolling and adhesion) in murine cerebral
      microvessels after transient bilateral carotid artery occlusion using intravital
      fluorescence microscopy. METHODS: We used 41 C57BL/6J mice for the experiment.
      Fourteen mice were used as sham group (no ischemia and reperfusion, no
      medication); an ischemia (induced by 15-minute occlusion of bilateral common
      carotid arteries) and reperfusion (I/R) group (n = 17); and an I/R + cilostazol
      (I/R + CZ) group (receiving 30 mg/kg of cilostazol orally at 30 minutes before
      ischemia) (n = 10). A cranial window was prepared in the right parietal region.
      Platelets obtained from donor mice were labeled with a fluorescent dye
      (carboxyfluorescein iodoacetate succinimidyl ester) in vitro. Labeled platelets
      were intravenously administered at 3 or 6 hours after reperfusion, and then
      platelet behavior (rolling and adhesion) in the brain microvessels was observed.
      The numbers of rolling and adhering platelets in the arteriole and venule were
      calculated. RESULTS: Numbers of rolling and adherent platelets at 3 and 6 hours
      after reperfusion were significantly higher in the I/R group than in the sham or
      I/R + CZ groups in both venule (P < .05) and arteriole (P < .05). CONCLUSIONS:
      Cilostazol inhibits platelet-endothelial interactions following cerebral ischemia
      and reperfusion.

PMID- 24135236
TI  - (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1
      one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-kappaB
      signaling pathway.
AB  - Our previous report has shown a natural pyranochalcones-derived compound, (E)-3
      (3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one
      (5b), that exerted protection against carrageenan-induced hind paw edema and
      adjuvant-induced arthritis. In this study, collagen-induced arthritis (CIA) model
      was used to further examine the anti-arthritic effects of 5b in vivo; the
      underlying molecular mechanisms of action were also investigated using a murine
      monocytic cell line, RAW264.7 cells. Here we showed that oral administration of
      5b (20mg/kg) significantly suppressed the progression of arthritis. Improvement
      in disease severity was accompanied by inhibition of CD68-positive cells in knee
      joint and reduced pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 in
      serum. In vitro, 5b suppressed expressions of iNOS, cyclooxygenase-2 (COX-2), TNF
      alpha, IL-6 and IL-1beta as well as productions of nitric oxide (NO) and
      prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated macrophages. This
      compound also significantly suppressed LPS-induced NF-kappaB activation,
      including phosphorylation of I-kappaB, degradation of I-kappaB, and nuclear
      translocation of p65 and p50. Treatment with 5b also blocked LPS-induced
      expression of TLR4 remarkably, suppressed degradation of IRAKs and
      phosphorylations of JNK and ERK, but had little effect to p38 kinase activation.
      These findings indicated that 5b might be a therapeutic agent for rheumatoid
      arthritis, and exerted an anti-inflammatory effect mainly through mediating TLR4,
      NF-kappaB and ERK/JNK signaling pathways in monocytes. 

PMID- 24135237
TI  - Dinoflagellate phylogeny revisited: using ribosomal proteins to resolve deep
      branching dinoflagellate clades.
AB  - The alveolates are composed of three major lineages, the ciliates,
      dinoflagellates, and apicomplexans. Together these 'protist' taxa play key roles
      in primary production and ecology, as well as in illness of humans and other
      animals. The interface between the dinoflagellate and apicomplexan clades has
      been an area of recent discovery, blurring the distinction between these two
      clades. Moreover, phylogenetic analysis has yet to determine the position of
      basal dinoflagellate clades hence the deepest branches of the dinoflagellate tree
      currently remain unresolved. Large-scale mRNA sequencing was applied to 11
      species of dinoflagellates, including strains of the syndinean genera
      Hematodinium and Amoebophrya, parasites of crustaceans and dinoflagellates,
      respectively, to optimize and update the dinoflagellate tree. From the
      transcriptome-scale data a total of 73 ribosomal protein-coding genes were
      selected for phylogeny. After individual gene orthology assessment, the genes
      were concatenated into a >15,000 amino acid alignment with 76 taxa from
      dinoflagellates, apicomplexans, ciliates, and the outgroup heterokonts. Overall
      the tree was well resolved and supported, when the data was subsampled with
      gblocks or constraint trees were tested with the approximately unbiased test. The
      deepest branches of the dinoflagellate tree can now be resolved with strong
      support, and provides a clearer view of the evolution of the distinctive traits
      of dinoflagellates. 

PMID- 24135238
TI  - New insights on the Golgi complex of Tritrichomonas foetus.
AB  - Tritrichomonas foetus is a protist that causes bovine trichomoniasis and presents
      a well-developed Golgi. There are very few studies concerning the Golgi in
      trichomonads. In this work, monoclonal antibodies were raised against Golgi of T.
      foetus and used as a tool on morphologic and biochemical studies of this
      organelle. Among the antibodies produced, one was named mAb anti-Golgi 20.3,
      which recognized specifically the Golgi complex by fluorescence and electron
      microscopy. By immunoblotting this antibody recognized two proteins with 60 and
      66 kDa that were identified as putative beta-tubulin and adenosine
      triphosphatase, respectively. The mAb 20.3 also recognized the Golgi complex of
      the Trichomonas vaginalis, a human parasite. In addition, the nucleotide coding
      sequences of these proteins were identified and included in the T. foetus
      database, and the 3D structure of the proteins was predicted. In conclusion, this
      study indicated: (1) adenosine triphosphatase is present in the Golgi, (2) ATPase
      is conserved between T. foetus and T. vaginalis, (3) there is new information
      concerning the nucleic acid sequences and protein structures of adenosine
      triphosphatase and beta-tubulin from T. foetus and (4) the mAb anti-Golgi 20.3 is
      a good Golgi marker and can be used in future studies.

PMID- 24135239
TI  - Comparison of lobe-specific mediastinal lymphadenectomy versus systematic
      mediastinal lymphadenectomy for clinical stage T1a N0 M0 non-small cell lung
      cancer.
AB  - OBJECTIVE: This study was to explore the appropriate extent of mediastinal lymph
      node dissection for clinical stage T1a N0 M0 non-small cell lung cancer (NSCLC)
      by comparison between two modes of mediastinal lymph node dissection. MATERIALS
      AND METHODS: A total of 96 clinical stage T1a N0 M0 NSCLC cases received radical
      surgery were randomly divided to lobe-specific mediastinal lymphadenectomy (LL)
      group and systematic mediastinal lymphadenectomy (SL) group from the year 2004 to
      2008. The effects of SL and LL on morbidity, N staging, overall survival (OS) and
      disease-free survival (DFS) were investigated. Meanwhile, associations between
      clinicopathological parameters and metastasis of lymph nodes were analyzed.
      RESULTS: The mean operating time and blood loss in LL group were significantly
      less than that in the SL group (135.48 +/- 25.44 min vs. 180.85 +/- 39.36 min,
      155.11 +/- 25.17 ml vs. 161.32 +/- 28.20 ml, P < 0.05), the mean numbers of
      dissected lymph nodes of the SL group was significantly greater than that in the
      LL group (17.1 +/- 3.7 vs. 9.4 +/- 2.1, P < 0.05). The post-operative overall
      morbidity rate was higher in the SL group than that in the LL group (P < 0.05).
      There were no significant difference in migration of N staging, OS and DFS
      between two groups. The post-operative N staging, the tumor cells differentiation
      and the ratio of ground glass opacity (GGO) in tumor were the independent factors
      influencing long-term survival. Moreover, the significant correlation was seen
      between the metastasis of lymph nodes and clinicopathological parameters
      including tumor location and the GGO ratio. CONCLUSION: The LL group had similar
      efficacy as the SL group in the clinical stage T1a N0 M0 NSCLC and there was
      unnecessary to perform systematic lymphadenectomy in such patients with a high
      ratio of GGO.

PMID- 24135240
TI  - Comparative study of the anatomic segmentectomy versus lobectomy for clinical
      stage IA peripheral lung cancer by video assistant thoracoscopic surgery.
AB  - OBJECTIVE: The objective of this study was to compare the completely
      thoracoscopic anatomic segmentectomy with lobectomy to treat stage I(A)
      peripheral lung cancer <2 cm. MATERIALS AND METHODS: A retrospective study was
      performed that 54 cases stage I(A) peripheral lung cancer patients were selected,
      including 26 cases of segmentectomy and 28 cases of lobectomy. We observed the
      operative time, blood loss, number of lymphadenectomy, post-operative chest
      drainage, hospital days, post-operative complications and mortality, post
      operative recurrence and 3-year survival rate. RESULTS: There was no significant
      difference about complications such as post-operative atelectasis, severe
      pneumonia, arrhythmia and cardiovascular/cerebrovascular in two groups (P >
      0.05). The local recurrence rate was not significant different in two groups (P >
      0.05). Two groups of operative time, blood loss and number of dissected lymph
      nodes was not statistically significant (P > 0.05), However, the difference was
      statistically significant in average chest drainage and less decreased pulmonary
      function, which led to patients received segmentectomy recovered faster and
      hospitalized less time (P < 0.05). We also found there was no significant
      difference on survival rate with 1 and 3 year follow-up of two groups (log-rank
      Chi-square = 0.028, P > 0.05). CONCLUSIONS: For stage I(A) peripheral lung
      cancer, the thoracoscopic anatomic segmentectomy was safe and effective just as
      thoracoscopic lobectomy, and furthermore with faster post-operative recovery.

PMID- 24135241
TI  - A severe dermatologic adverse effect related with gefitinib: case report and
      review of the literature.
AB  - Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine
      kinase, it's one of the most frequent drug-related adverse effects (AEs) reported
      in literature is dermatologic AEs. We report, a case of severe cutaneous adverse
      reactions induced by gefitinib as second-line treatment in a male patient with
      advanced non-small cell lung cancer after 1 month of treatment. Although tumor
      shrunk and patient got benefit from the treatment, gefitinib had to be stopped
      right away. We managed the symptoms of rash with a variety of treatments,
      including topical ethacridine lactate, antihistamine and so on. After the rash
      improved, we found his tumor were progress. Then he took gefitinib again without
      severe skin toxicity or disease progression. We think the development of
      gefitinib-induced rash may be a sign of effective and administrating it again
      maybe relieves the degree of rash. 

PMID- 24135242
TI  - A case of parachordoma on the chest wall and literature review.
AB  - Parachordoma is an extremely uncommon soft-tissue tumor, which mainly occurs in
      the deep soft-tissue of the distal parts of the limbs, such as deep fascia,
      muscle tendon, synovial or soft-tissue closed to the bone. Nevertheless, the
      literature reports about parachordoma on the thoracic wall were scarce. The
      clinical and imaging manifestation has a non-specific appearance. In this
      article, we reported one case of parachordoma of the thoracic wall that we met in
      clinical works and reviewed the literature. 

PMID- 24135243
TI  - Spontaneous pneumothorax as the initial manifestation of stage IB primary
      pulmonary carcinoma: really early stage cancer?
AB  - Spontaneous pneumothorax (SP) is a rare manifestation of lung cancers, especially
      as the first sign. The mechanism producing pneumothorax from pulmonary cancer has
      three main reasons, One is that the cancer necrosis directly ruptured into the
      pleural space. Another is that endobronchial neoplasm acts as a check valve,
      leading to dilation and eventual rupture of distal alveolar spaces. The third is
      that the rupture of small subpleural blebs accidentally causes SP. However, the
      prognosis of lung cancer patients with initial manifestation of SP is very poor,
      SP seems to be an ominous sign for the primary cavity lung cancer patients, even
      in an early stage. 

PMID- 24135244
TI  - The challenges of lung cancer in China.

PMID- 24135245
TI  - Signal transducers and activators of transcription 3 function in lung cancer.
AB  - Constitutively activation of signal transducers and activators of transcription 3
      (STAT3) proteins are involved in multiple aberrant signaling pathway-oncogenic
      pathways, including pathways regulating tumor cell survival. STAT3 is one of the
      second messengers in the Janus activated family kinases/STAT signaling pathway
      and is regulated by many different factors involving tumorigenesis. Given that
      the activation of STAT3 is observed in nearly 50% of Lung cancers and more and
      more researches regarding STAT3 in tumors, here in, we reviewed the contribution
      of STAT3 to lung cancer growth and progression and then the context in which
      positive and negative regulation of STAT activation leading to cell competition
      provides a mechanism for therapeutic intervention for specific cancers is
      discussed. 

PMID- 24135246
TI  - Protein kinase Cs in lung cancer: a promising target for therapies.
AB  - Lung cancer has been identified as one of the most deadly oncologies. The most
      influential causes for disease progression include smoking, genetic mutation and
      inflammatory lung diseases. Conventional therapies for lung cancer including
      chemo and radio-treatments often cause serious adverse effects. The advent of
      novel therapeutics that specifically target signalling pathways activated by
      genetic alterations has revolutionized the way patients with lung cancer are
      treated. These are comprised of various molecular targets on its carcinogen
      signalling pathways, among which the protein kinase C (PKC) family is a promising
      target. The 12 isotypes in the family demonstrate complex interactions. This
      inter-linked signalling loop has added complexity of developing effective
      therapies. An improved understanding of different molecules involved in these
      signalling pathways will provide several profound implications, ranging from
      preclinical work on the mechanisms to trial design. Therapies developed targeting
      individual/multiple PKCs combined with conventional strategies offer promising
      future combating cancer. 

PMID- 24135247
TI  - The regulation of cell polarity in the progression of lung cancer.
AB  - Lung cancer is the most frequent malignant disease, since it has often
      metastasized to distant organs by the time of diagnosis. Epithelial-mesenchymal
      transition (EMT) is an important process during the progression of lung cancer.
      Epithelial cells lose the polarity, which contributes to uncontrolled invasion
      and metastasis of cancer cells. Cell polarity establishment and maintenance
      depends upon the three complex proteins which are par, crumbs and scribble
      complexes, of which are reported as tumor suppressors. The cell polarity proteins
      could interact with cell-cell contact and cell-extracellular matrix contact and
      cell-intrinsic signaling. These interactions are proved to be involved in lung
      cancer metastasis. However, our understanding of the mechanisms by which this
      occurs is poor. In this review, we will discuss the regulatory network of cell
      polarity in the lung cancer, especially on EMT. 

PMID- 24135248
TI  - The landscape of histone acetylation involved in epithelial-mesenchymal
      transition in lung cancer.
AB  - Epithelial-mesenchymal transition (EMT) has been widely accepted as the early
      stage of tumor metastasis, which is accomplished by a group of transcription
      factors based on cancer genome. However, with the progress of epigenome profiling
      technique, it has been demonstrated that aberrant histone modifications
      especially acetylation play an important role in EMT and cancer metastasis.
      Besides this, numerous studies have elucidated the mechanisms of histone
      acetyltransferases and deacetylases involved in EMT. Moreover, the network of
      these histone-related proteins and those transcription factors that play key
      roles in EMT is under increasing investigation. In addition, the crosstalk among
      deoxyribonucleic acid methylation, histone acetylation and micro Ribonucleic
      acid, three major epigenetic modifications, is also an important part in tumor
      progression. Here, we explore the mechanisms of histone acetylation in EMT and
      discuss the potential clinical strategies using the epigenetic drugs. 

PMID- 24135249
TI  - Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer.
AB  - OBJECTIVE: The purpose of this study is to analyze a single institution
      experience with pleuropneumonectomy for pleural metastasis and malignant pleural
      effusion in primary lung cancer. MATERIALS AND METHODS: From August 1978 to
      August 2011, 66 consecutive patients with lung cancer underwent
      pleuropneumonectomy. Patients were followed-up after the operation. The quality
      of-life and the survival time were recorded. RESULTS: All the 66 patients were
      successfully operated on, including 38 patients in early years (1978-1993) and 28
      patients in recent years (1994-2011). Two patients in early years died after the
      operation. Post-operative complications occurred including heart arrhythmia,
      respiratory insufficiency and bacterial infection of residual lung, chylothoraxin
      and mental disorder. A total of 61 patients have been successfully followed-up
      and three patients in early years were lost in 1 year after the operation. Local
      recurrence was found in seven cases (4 in early years, 3 in recent years) and
      distant metastasis was found in 48 cases (29 in early years, 19 in recent years).
      A total of 54 patients died from tumors, seven patients survived. The actuarial
      1, 2 and 3-year survival rates are 72.7%, 27.2% and 6.1% of 36 in patients of
      early years and 85.7%, 46.4% and 21.4% in 28 patients of recent years. The mean
      survival and the median survival of the total 64 patients were 20.0 +/- 10.9
      months and 17 months respectively. Further analysis showed that the mean survival
      and the median survival of the 36 patients in early years were 17.2 +/- 9.7
      months and 15 months, in contrast to 23.4 +/- 11.3 months and 18 months of the 28
      patients in recent years. CONCLUSION: Pleuropneumonectomy is an option of
      patients with advanced-stage lung cancer associated with uncontrolled malignant
      pleural fluid by conservative therapies. Strict selection of patient to be
      operated, careful procedures to eradicate obvious tumors and metastasis and
      enhanced post-operative combined therapy are beneficial to patients' long-term
      survival.

PMID- 24135250
TI  - Association between clinical pathology and multiple genes mRNA expression in
      Chinese patients with NSCLC.
AB  - OBJECTIVE: The aim of this study was to evaluate whether there was an association
      between pathology type and ERCC1, BRCA1, RRM1, TUBB3, STMN1, TOP2A and epidermal
      growth factor receptor (EGFR) messenger ribonucleic acid (mRNA) expression level
      in Chinese patients with non-small cell lung carcinoma (NSCLC). MATERIALS AND
      METHODS: mRNA expression level of these genes was analyzed in 181 cancer tissues
      by using xTAG-step liquid-chip array. The mRNA expression level of the seven
      genes was evaluated in association with the clinical pathology type. RESULTS: The
      average mRNA expression level of the seven genes were ERCC1 (1.02 +/- 0.03),
      BRCA1 (0.15 +/- 0.04), RRM1 (0.19 +/- 0.05), TUBB3 (0.31 +/- 0.06), STMN1 (2.78
      +/- 0.42), TOP2A (3.04 +/- 0.42) and EGFR (0.58 +/- 0.09), respectively in
      Chinese patients with NSCLC. The mRNA expression level of ERCC1, STMN1 and TOP2A
      genes were statistical different with different pathology type (p(a) < 0.05);
      STMN1 and TOP2A genes mRNA expression were much higher in squamous cell lung
      carcinoma than that in non-squamous cell lung carcinoma (p(a) < 0.05). And ERCC1
      gene expression was much lower in squamous cell carcinoma than that in non
      squamous cell carcinoma (p(a) < 0.05). CONCLUSION: mRNA expression level of
      STMN1, TOP2A and ERCC1 were correlated with the clinical pathology type.

PMID- 24135251
TI  - The significance of augmented high-grade squamous intraepithelial lesion
      detection on pap test examination: partial results from the RODEO study team.
AB  - OBJECTIVE: This study sought to ascertain the significance of augmented high
      grade squamous intraepithelial lesion (HSIL) detection by Pap test using both
      conventional smear and liquid-based cytology (LBC) in a high-risk population.
      STUDY DESIGN: We conducted a direct-to-vial study to compare the diagnostic
      performance of Pap smear versus LBC in a high-risk population of women referred
      for colposcopy at a gynecologic ambulatory clinic at the Barretos Cancer Hospital
      in Brazil during 2011. RESULTS: The detection of both low-grade squamous
      intraepithelial lesions (LSILs) and HSILs was significantly greater (p = 0.04 and
      p = 0.033, respectively) in the LBC arm [84 LSIL cases (5.7%) and 148 HSIL cases
      (10.1%)] than in the conventional smear arm [66 LSIL cases (4.1%) and 126 HSIL
      cases (7.9%)]; however, no differences were found for invasive squamous carcinoma
      or adenocarcinoma (p = 0.678). Of 3,071 women who were examined cytologically
      (1,604 conventional preparations and 1,467 LBC) and colposcopically, biopsies
      were available for 279 conventional preparations (17.6%) and 325 LBC preparations
      (22.2%). No significant differences were found between the methods with respect
      to diagnostic performance. CONCLUSION: LBC was significantly superior to
      conventional smears for the detection of LSILs and HSILs, but these results did
      not influence biopsy confirmation. Both methods showed similar performances with
      high positive predictive values but very low sensitivities.

PMID- 24135252
TI  - Do we really need new medical information about the Turin Shroud?
AB  - Image processing of the Turin Shroud (TS) shows that the Man represented in it
      has undergone an under glenoidal dislocation of the humerus on the right side and
      lowering of the shoulder, and has a flattened hand and enophthalmos; conditions
      that have not been described before, despite several studies on the subject.
      These injuries indicate that the Man suffered a violent blunt trauma to the neck,
      chest and shoulder from behind, causing neuromuscular damage and lesions of the
      entire brachial plexus. The posture of the left claw-hand is indicative of an
      injury of the lower brachial plexus, as is the crossing of the hands on the
      pubis, not above the pubis as it would normally be, and are related to traction
      of the limbs as a result of the nailing to the patibulum. The disappearance of
      the thumbprints is because of entrainment of the flexor pollicis longus tendons
      while the nails were driven through the wrists. The blunt chest trauma, which
      resulted in the body falling forwards, was the direct cause of a lung contusion
      and haemothorax, confirmed by the post-mortem leakage of clots and serum from the
      chest caused by the stabbing with the spear, and was a likely cause of cardiac
      contusion. All the evidence is in favour of the hypothesis that the TS Man is
      Jesus of Nazareth. 

PMID- 24135253
TI  - Quantitative evaluation of cortical bone thickness in mandibular prognathic
      patients with neurosensory disturbance after bilateral sagittal split osteotomy.
AB  - PURPOSE: The buccal cortical thickness (BCT) between the mandibular canal and the
      corresponding external cortical surface was compared in patients with and without
      neurosensory disturbance (NSD) after they underwent a bilateral sagittal split
      osteotomy (BSSO) to correct mandibular prognathism. PATIENTS AND METHODS: This
      prospective cohort study was conducted in 146 patients (95 women, 65.1%; 51 men,
      34.9%) 18 to 39 years old who underwent bimaxillary surgery (ie, Le Fort I
      osteotomy and BSSO) to correct mandibular prognathism. NSD was identified using a
      light touch test with a Semmes-Weinstein monofilament and a pricking pain test
      with a sharp dental explorer 1 week after surgery. Preoperative cone-beam
      computed tomographic (CBCT) imaging was used to visualize the bone contacts or
      fusion of the mandibular canal to the buccal cortical bone and to decrease injury
      to the mandibular nerve during surgical dissection. Preoperative CBCT imaging
      also was used to assess the BCT every 2 mm from the mandibular foramen to the
      furcation of the mandibular first molar in the NSD group and the sensory normal
      (N) group. RESULTS: The incidence of NSD was 32.5% at 1 week after surgery. There
      was no statistically significant difference between men and women, the side
      affected, or genioplasty at the time of undergoing BSSO. Of the total sample
      group, decreased BCT was identified throughout the observed length of the
      mandibular canal in the NSD group compared with the N group. Statistically
      significant decreased BCTs were 16 to 20 mm and 24 mm in the total sample, 6 to 8
      mm in the female group, and 16 to 18 mm in the male group. CONCLUSION: Compared
      with the N group, BCTs in the NSD group were always decreased, especially those
      located at 16 to 20 mm and 24 mm in the total sample, 6 to 8 mm in the female
      group, and 16 to 18 mm in the male group.

PMID- 24135254
TI  - Immunogenicity of a modified intradermal pre-exposure rabies vaccination schedule
      using a purified chick embryo cell vaccine: an observational study.
AB  - BACKGROUND: In Australia, recommendations for pre-exposure rabies vaccination
      involve 3 doses of vaccines on days 0, 7, and 28 using either 1.0 mL
      intramuscular (IM) vaccines, or 0.1 mL intradermal (ID) vaccines. The use of IM
      vaccines is limited by their prohibitive cost, and ID vaccines by the
      recommendation for serology 2-3 weeks post-vaccination. A recent study reported
      the successful use of human diploid cell rabies vaccines (HDCV) with a modified
      ID schedule (2 * 0.1 mL ID on days 0 and 7) - Travellers Rabies Intradermal 2
      site (TRID2) - that was affordable, required less time to complete than standard
      ID schedules, and achieved a seroconversion rate of 94.5%. This study reports the
      immunogenicity of pre-exposure rabies vaccination using a purified chick embryo
      cell vaccine (PCECV) with the TRID2 schedule. METHOD: Travellers aged 10-50 years
      were given the PCECV using the TRID2 schedule, and serology was performed at day
      28. RESULTS: Fifty-four travellers were vaccinated, with a seroconversion rate of
      94.4% at day 28. Seroconversion rates did not differ between age groups, but
      older travellers had lower antibody levels. CONCLUSIONS: This study supports the
      effectiveness of the TRID2 schedule, and found the schedule equally effective
      with HDCV or PCECV.

PMID- 24135255
TI  - Skittish, shielded, and scared: relations among behavioral inhibition,
      overprotective parenting, and anxiety in native and non-native Dutch preschool
      children.
AB  - This study examined behavioral inhibition and overprotective parenting as
      correlates and predictors of anxiety disorder symptoms in preschoolers with a
      multi-cultural background (N=168). Parents of 3- to 6-year-old children completed
      a set of questionnaires twice, 12 months apart. Parents were also interviewed
      with the Anxiety Disorders Interview Schedule for DSM-IV at the 12-month point to
      assess the clinical severity of children's anxiety symptoms. Behavioral
      inhibition consistently emerged as a significant concurrent correlate of anxiety
      symptoms and this was particularly true for social anxiety symptoms.
      Overprotective parenting also emerged as a significant correlate of anxiety, but
      only in the case of non-social anxiety symptoms and mainly in non-native Dutch
      children. Prospective analyses revealed that behavioral inhibition was a
      significant predictor of social anxiety symptoms, while overprotective parenting
      did not explain significant variance in the development of children's anxiety
      over time. The support for an interactive effect of behavioral inhibition and
      overprotective parenting was unconvincing. Finally, it was found that children
      who exhibited stable high levels of behavioral inhibition throughout the study
      ran the greatest risk for developing an anxiety disorder. 

PMID- 24135256
TI  - Psychometric properties of the Child Anxiety Life Interference Scale (CALIS).
AB  - This paper describes the development and psychometric evaluation of a parent and
      child report measure of life interference and impairment associated with
      childhood anxiety, the Child Anxiety Life Interference Scale (CALIS). The CALIS
      is designed to measure life interference and impairment experienced by the child
      from the child (9 items) and parent (16 items) point of view and also the
      interference experienced by the parent in their own life. A total of 622 children
      between 6 and 17 years of age, and their parents, completed the CALIS. Results
      indicated that the CALIS has good internal consistency, moderate-to-high test re
      test reliability, significant inter rater reliability, good convergent and
      divergent validity and is sensitive to treatment change. The CALIS is a reliable
      and valid tool for the assessment of life interference and impairment associated
      with anxiety disorders in childhood. 

PMID- 24135257
TI  - Incremental direct medical expenditures associated with anxiety disorders for the
      U.S. adult population: evidence from the Medical Expenditure Panel Survey.
AB  - Data from the 2009 and 2010 Medical Expenditure Panel Survey (MEPS) were used to
      estimate the annual incremental healthcare expenditures associated with anxiety
      disorders, for the ambulatory adult population of the U.S. Individuals 18 years
      and older, who reported a diagnosis of, or had a medical event associated with
      anxiety disorder(s), were classified as anxiety population. Multivariate
      regression analyses, using generalized linear models, were conducted to calculate
      incremental costs associated with anxiety disorders. 8.74% of adult respondents
      reported being diagnosed with anxiety disorder(s). The annual overall healthcare
      expenditure associated with anxiety disorders was estimated at $1657.52 per
      person (SE: $238.83; p<0.001). Inpatient visits, prescription medications, and
      office-based visits together accounted for almost 93% of the overall cost. Given
      the prevalence of self-reported anxiety disorders in MEPS, their total direct
      medical expenditure is estimated at approximately $33.71 billion in 2013 US
      dollars, meaning this category of mental illnesses absorbs a significant portion
      of the U.S. healthcare resources. 

PMID- 24135258
TI  - Pre-school manager training: a cost-effective tool to promote nutrition- and
      health-related practice improvements in the Irish full-day-care pre-school
      setting.
AB  - OBJECTIVE: To evaluate the impact on nutrition- and health-related practice of
      two methods of delivery of a nutrition and health intervention in Irish full-day
      care pre-schools: training of pre-school managers only or training of managers
      and their staff. DESIGN: A simple randomised study with pre-schools divided into
      two training groups: 'manager trained' and 'manager and staff trained'. Direct
      observational data--food and fluid provision, physical activity, outdoor time,
      staff practices and availability of nutrition and health resources--were recorded
      during one full day spent in each pre-school both pre- and post-intervention,
      using a specifically developed and validated Pre-school Health Promotion Activity
      Scored Evaluation Form. Post-intervention, self-assessment data were also
      collected using the same evaluation tool. SETTING: Pre-schools, Midlands of
      Ireland. SUBJECTS: A convenience sample of forty-two pre-schools registered with
      the Irish Health Service Executive. RESULTS: From pre- to post-intervention,
      significant improvement (P < 0.05) in nutrition- and health-related practice was
      observed within both intervention delivery groups in all areas evaluated:
      environment, food service, meals and snacks. No additional effect attributable to
      staff training was observed. Scores assigned by direct independent observation
      were lower than pre-school self-assessment scores. CONCLUSIONS: The
      implementation of a training intervention in pre-schools significantly improved
      practice with no significant benefit of additional staff training. Direct
      independent observation is required to quantify practice accurately.

PMID- 24135259
TI  - Impact of a stance phase microprocessor-controlled knee prosthesis on level
      walking in lower functioning individuals with a transfemoral amputation.
AB  - BACKGROUND: For individuals with transfemoral amputation, walking with a
      prosthesis presents challenges to stability and increases the demand on the hip
      of the prosthetic limb. Increasing age or comorbidities magnify these challenges.
      Computerized prosthetic knee joints improve stability and efficiency of gait, but
      are seldom prescribed for less physically capable walkers who may benefit from
      them. OBJECTIVE: To compare level walking function while wearing a microprocessor
      controlled knee (C-Leg Compact) prosthesis to a traditionally prescribed non
      microprocessor-controlled knee prosthesis for Medicare Functional Classification
      Level K-2 walkers. STUDY DESIGN: Crossover. METHODS: Stride characteristics,
      kinematics, kinetics, and electromyographic activity were recorded in 10
      participants while walking with non-microprocessor-controlled knee and Compact
      prostheses. RESULTS: Walking with the Compact produced significant increase in
      velocity, cadence, stride length, single-limb support, and heel-rise timing
      compared to walking with the non-microprocessor-controlled knee prosthesis. Hip
      and thigh extension during late stance improved bilaterally. Ankle dorsiflexion,
      knee extension, and hip flexion moments of the prosthetic limb were significantly
      improved. CONCLUSIONS: Improvements in walking function and stability on the
      prosthetic limb were demonstrated by the K-2 level walkers when using the C-Leg
      Compact prosthesis. CLINICAL RELEVANCE: Understanding the impact of new
      prosthetic designs on gait mechanics is essential to improve prescription
      guidelines for deconditioned or older persons with transfemoral amputation.
      Prosthetic designs that improve stability for safety and walking function have
      the potential to improve community participation and quality of life.

PMID- 24135260
TI  - Exploring eHealth Ethics and Multi-Morbidity: Protocol for an Interview and Focus
      Group Study of Patient and Health Care Provider Views and Experiences of Using
      Digital Media for Health Purposes.
AB  - BACKGROUND: eHealth is a broad term referring to the application of information
      and communication technologies in the health sector, ranging from health records
      to medical consultations (telemedicine) and multiple forms of health education,
      support, and tools. By providing increased and anytime access to information,
      opportunities to exchange experiences with others, and self-management support,
      eHealth has been heralded as transformational. It has the potential to accelerate
      the shift from traditional "passive patient" to an informed, engaged, and
      empowered "patient as partner," equipped to take part in shared decision-making,
      and take personal responsibility for self-managing their illness. OBJECTIVE: The
      objective of our study is to examine how people with chronic illness use eHealth
      in their daily lives, how it affects patient-provider relationships, and the
      ethical and practical ramifications for patients, providers, and service
      delivery. METHODS: This two-phase qualitative study is ongoing. We will
      purposively sample 60-70 participants in British Columbia, Canada. To be
      eligible, patient participants have to have arthritis and at least one other
      chronic health condition; health care providers (HCPs) need a caseload of
      patients with multi-morbidity (>25%). To date we have recruited 36 participants
      (18 patients, 18 HCPs). The participants attended 7 focus groups (FGs), 4 with
      patients and 3 with rehabilitation professionals and physicians. We interviewed 4
      HCPs who were unable to attend a FG. In phase 2, we will build on FG findings and
      conduct 20-24 interviews with equal numbers of patients and HCPs (rehabilitation
      professionals and physicians). As in the FGs conducted in phase I, the interviews
      will use a semistructured, but flexible, discussion guide. All discussions are
      being audiotaped and transcribed verbatim. Constant comparisons and a narrative
      approach guides the analyses. A relational ethics conceptual lens is being
      applied to the data to identify emergent ethical issues. RESULTS: This study
      explores ethical issues in eHealth. Our goal is to identify the role of eHealth
      in the lives of people with multiple chronic health conditions and to explore how
      eHealth impacts the patient role, self-managing, and the patient-HCP
      relationship. The ethical lens facilitates a systematic critical analysis of
      emergent ethical issues for further investigation and pinpoints areas of practice
      that require interventions as eHealth develops and use increases both within and
      outside of the clinical setting. CONCLUSIONS: The potential benefits and burdens
      of eHealth need to be identified before an ethical framework can be devised.

PMID- 24135261
TI  - Are graph databases ready for bioinformatics?

PMID- 24135262
TI  - Automated prior knowledge-based quantification of neuronal patterns in the spinal
      cord of zebrafish.
AB  - MOTIVATION: To reliably assess the effects of unknown chemicals on the
      development of fluorescently labeled sensory-, moto- and interneuron populations
      in the spinal cord of zebrafish, automated data analysis is essential. RESULTS:
      For the evaluation of a high-throughput screen of a large chemical library, we
      developed a new method for the automated extraction of quantitative information
      from green fluorescent protein (eGFP) and red fluorescent protein (RFP) labeled
      spinal cord neurons in double-transgenic zebrafish embryos. The methodology
      comprises region of interest detection, intensity profiling with reference
      comparison and neuron distribution histograms. All methods were validated on a
      manually evaluated pilot study using a Notch inhibitor dose-response experiment.
      The automated evaluation showed superior performance to manual investigation
      regarding time consumption, information detail and reproducibility. AVAILABILITY
      AND IMPLEMENTATION: Being part of GNU General Public Licence (GNU-GPL) licensed
      open-source MATLAB toolbox Gait-CAD, an implementation of the presented methods
      is publicly available for download at
      http://sourceforge.net/projects/zebrafishimage/.

PMID- 24135263
TI  - Discretized Gaussian mixture for genotyping of microsatellite loci containing
      homopolymer runs.
AB  - MOTIVATION: Inferring lengths of inherited microsatellite alleles with single
      base pair resolution from short sequence reads is challenging due to several
      sources of noise caused by the repetitive nature of microsatellites and the
      technologies used to generate raw sequence data. RESULTS: We have developed a
      program, GenoTan, using a discretized Gaussian mixture model combined with a
      rules-based approach to identify inherited variation of microsatellite loci from
      short sequence reads without paired-end information. It effectively distinguishes
      length variants from noise including insertion/deletion errors in homopolymer
      runs by addressing the bidirectional aspect of insertion and deletion errors in
      sequence reads. Here we first introduce a homopolymer decomposition method which
      estimates error bias toward insertion or deletion in homopolymer sequence runs.
      Combining these approaches, GenoTan was able to genotype 94.9% of microsatellite
      loci accurately from simulated data with 40x sequence coverage quickly while the
      other programs showed <90% correct calls for the same data and required 5~30*
      more computational time than GenoTan. It also showed the highest true-positive
      rate for real data using mixed sequence data of two Drosophila inbred lines,
      which was a novel validation approach for genotyping. AVAILABILITY: GenoTan is
      open-source software available at http://genotan.sourceforge.net.

PMID- 24135264
TI  - Frequent glycan structure mining of influenza virus data revealed a sulfated
      glycan motif that increased viral infection.
AB  - MOTIVATION: It is well known influenza viruses recognize and bind terminal sialic
      acid (SA) on glycans that are found on the cell surface. In this work, we used a
      data mining technique to analyze the glycan array data of influenza viruses to
      find novel glycan structures other than SA that may be involved in viral
      infection. RESULTS: In addition to SA structures noted previously, we noted the
      sulfated structures in the mining results. For verification, we overexpressed the
      sulfotransferase that is involved in synthesizing these structures, and we
      performed a viral infection experiment to assess changes in infection in these
      cells. In our results, we found that there is a 70-fold increase in these cells
      compared with the control. Thus, we have found a novel pattern in glycan
      structures that may be involved in viral infection. AVAILABILITY AND
      IMPLEMENTATION: The Glycan Miner Tool is available from the RINGS resource at
      http://www.rings.t.soka.ac.jp.

PMID- 24135265
TI  - A probabilistic approach to explore human miRNA targetome by integrating miRNA
      overexpression data and sequence information.
AB  - MOTIVATION: Systematic identification of microRNA (miRNA) targets remains a
      challenge. The miRNA overexpression coupled with genome-wide expression profiling
      is a promising new approach and calls for a new method that integrates expression
      and sequence information. RESULTS: We developed a probabilistic scoring method
      called targetScore. TargetScore infers miRNA targets as the transformed fold
      changes weighted by the Bayesian posteriors given observed target features. To
      this end, we compiled 84 datasets from Gene Expression Omnibus corresponding to
      77 human tissue or cells and 113 distinct transfected miRNAs. Comparing with
      other methods, targetScore achieves significantly higher accuracy in identifying
      known targets in most tests. Moreover, the confidence targets from targetScore
      exhibit comparable protein downregulation and are more significantly enriched for
      Gene Ontology terms. Using targetScore, we explored oncomir-oncogenes network and
      predicted several potential cancer-related miRNA-messenger RNA interactions.
      AVAILABILITY AND IMPLEMENTATION: TargetScore is available at Bioconductor:
      http://www.bioconductor.org/packages/devel/bioc/html/TargetScore.html.

PMID- 24135266
TI  - Simvastatin reduces CCL2 expression in monocyte-derived cells by induction of a
      repressive CCL2 chromatin state.
AB  - Statins exert anti-inflammatory characteristics, besides their lipid lowering
      properties, and may display beneficial effects for the treatment of inflammatory
      diseases. One possible explanation is that statins interfere in the deregulated
      gene transcription patterns associated with immune-mediated diseases, although
      the precise mechanism is not fully understood. Besides gene regulatory proteins,
      epigenetic mechanisms play an important role in the orchestration of gene
      expression. Disturbances in the tightly controlled epigenetic mechanisms
      influence the cellular portrait of expressed genes resulting in the protein
      dysfunctions found in many inflammatory diseases. In this study, we found that
      simvastatin reduces secretion and gene expression of CCL2 in monocyte-derived
      immature dendritic cells and in type 1 macrophages, which is accompanied by
      increased levels of the 3meK27H3 and 3meK9H3 repressive histone marks and
      decreased levels of the permissive histone marks AcH3 and 3meK4H3 in CCL2
      promoter chromatin. The repressive chromatin status of the CCL2 promoter region
      affected recruitment of the NF-kappaB p65 subunit, which controls CCL2
      transcription. The down-regulation of CCL2 in these immune cells may therefore
      impact their chemotactic activity and reduce their recruitment to sites of tissue
      injury. 

PMID- 24135267
TI  - In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S
      quantum dots in the NIR-II window.
AB  - Improving the tissue penetration depth and spatial resolution of fluorescence
      based optical nanoprobes remains a grand challenge for their practical
      applications in in vivo imaging, due to the scattering and absorption and
      endogenous autofluorescence of living tissues. Here, we present that Ag2S quantum
      dots (QDs), containing no toxic ions, exhibiting long circulation time and high
      stability, act as a new kind of fluorescent probes in the second near-infrared
      window (NIR-II, 1000-1350 nm) which enable in vivo monitoring of lymphatic
      drainage and vascular networks with deep tissue penetration and high spatial and
      temporal resolution. In addition, NIR-II fluorescence imaging with Ag2S QDs
      provide ultrahigh spatial resolution (~40 MUm) that permits us to track
      angiogenesis mediated by a tiny tumor (2-3 mm in diameter) in vivo. Our results
      indicate that Ag2S QDs are promising NIR-II fluorescent nanoprobes that could be
      useful in surgical treatments such as sentinel lymph node (SLN) dissection as
      well in assessment of blood supply in tissues and organs and screening of anti
      angiogenic drugs.

PMID- 24135268
TI  - Biodegradable self-assembled nanoparticles of poly (D,L-lactide-co
      glycolide)/hyaluronic acid block copolymers for target delivery of docetaxel to
      breast cancer.
AB  - To develop biodegradable docetaxel-loaded self-assembled nanoparticles of poly
      (D,L-lactide-co-glycolide)/hyaluronic acid block copolymers were successfully
      synthesized. These copolymers could form nanoparticles with small size (<200 nm),
      an acceptable CMC (~7.9 mg/L), typical core/shell structure and superior
      stability in one week. DTX-loaded PLGA(502H)-b-HA(5.6k) nanoparticles (DTX/SANPs)
      showed a biphasic release pattern within 120 h, and exhibited enhanced
      cytotoxicity toward CD44-overexpressing MDA-MB-231 cells. Cellular uptake study
      indicated that PLGA(502H)-b-HA(5.6k) nanoparticles (SANPs) were taken up in MDA
      MB-231 cells by CD44-mediated endocytosis. Pharmacokinetics study revealed
      DTX/SANPs could prolong the circulation of DTX in the blood. In vivo studies
      demonstrated that SANPs exhibited enhanced tumor targeting and antitumor activity
      with lower systemic toxicity. In conclusion, DTX/SANPs have great potential for
      targeted chemotherapy for CD44-overexpressing breast cancer.

PMID- 24135269
TI  - The influence of Gelatin/PCL ratio and 3-D construct shape of electrospun
      membranes on cartilage regeneration.
AB  - Scaffolds play an important role in directing three-dimensional (3-D) cartilage
      regeneration. Our recent study reported the potential advantages of electrospun
      gelatin/polycaprolactone (GT/PCL) membranes in regenerating 3-D cartilage.
      However, it is still unknown whether the changes of GT/PCL ratio have significant
      influence on 3-D cartilage regeneration. To address this issue, the current study
      prepared three kinds of electrospun membranes with different GT/PCL ratios
      (70:30, 50:50, 30:70). Adhesion and proliferation of chondrocytes on the
      membranes were examined to evaluate biocompatibility of the membranes. Cartilage
      with different 3-D shapes was engineered to further evaluate the influences of
      GT/PCL ratio on cartilage regeneration. The current results demonstrated that all
      the membranes with different GT/PCL ratios presented good biocompatibility with
      chondrocytes. Nevertheless, the high PCL content in the membranes significantly
      hampered early 3-D cartilage formation at 3 weeks in vivo. Unexpectedly, at 12
      weeks, all the cylinder-shaped constructs formed mature cartilage-like tissue
      with no statistical differences among groups. To our surprise, ear-shaped
      cartilage regeneration obtained quite different results again: the high PCL
      content completely disrupted cartilage regeneration even at 12 weeks, and only
      the least PCL content group formed homogeneous and continuous cartilage with a
      satisfactory shape and elasticity similar to human ear. All these results
      indicated that the high PCL content was unfavorable for 3-D cartilage
      regeneration, especially for the cartilage with a complicated shape, and that
      GT/PCL 70:30 might be a relatively suitable ratio for ear-shaped cartilage
      regeneration. The research models established in the current study provide
      detailed information for cartilage and other tissue regeneration based on
      electrospun GT/PCL membranes.

PMID- 24135270
TI  - Vemurafenib as a neoadjuvant therapy in advanced melanoma: local tumour control,
      but no prevention of metastatic relapse.

PMID- 24135271
TI  - An Intra-tendonous ganglion cyst causing impingement between the anterior
      cruciate ligament and anterior root of the medial meniscus: a case report.
AB  - BACKGROUND: There are several reports of symptomatic ganglion cysts near the
      anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and lateral
      and medial meniscus, but symptomatic ganglia arising from the anterior horn of
      the medial meniscus to the ACL have not been reported. Here we report the
      arthroscopic resection of a ganglion cyst arising from the anterior horn of the
      medial meniscus with a meniscal tear to the ACL. CASE PRESENTATION: A 43-year-old
      female presented with a 10-year history of continuous aching pain in the right
      knee, but without any history of trauma. Clinical examination revealed right
      sided knee pain in the medial joint line, exacerbated by end range flexion and
      extension, a -10 degrees -100 degrees  active range of movement, and a -5 degrees
      -110 degrees  passive range of movement?McMurray's, patellar compression, and
      compression rotation tests were positive. Magnetic resonance imaging (MRI) and
      arthroscopic examination revealed a cyst related to the ACL and medial meniscus.
      Histological examination confirmed the cyst to be a ganglion cyst. CONCLUSIONS:
      We present a new type of ganglion cyst, this is the first reported case of an
      ganglion cyst impinged between the ACL and the medial meniscus. It is hoped that
      this study will provide a better understanding of the condition and lead to
      better diagnosis and treatment.

PMID- 24135272
TI  - Influence of introduced vs. native parasites on the body condition of migrant
      silver eels.
AB  - Because parasitism is among the reasons invoked to explain the collapse of
      Anguilla anguilla, we evaluated the parasitic constraint on body condition (BC)
      of migrant silver eels as a proxy of fitness with inter-site comparisons.
      Metazoan parasites were studied in 149 silver eels from five sites (northern
      Europe). In total, 89% were infected by 13 species including Myxozoa, Monogenea,
      Cestoda, Nematoda, and Acanthocephala. Anguillicoloides crassus was most common
      (56%), then Acanthocephalus clavula (30%), and Pseudodactylogyrus sp. (17%). BC,
      calculated for 58 females, was negatively correlated by abundance of the
      introduced Pseudodactylogyrus sp. but not by other parasite taxa. Nevertheless,
      the introduced A. crassus was considered as a severe pathogen based on previous
      data, whereas the native A. clavula was supposed to have limited impact. Parasite
      component communities and BC were different between sites. Silver eels from
      Stockholm Archipelago (Sweden) were the least parasitized (40% vs. 90-95% for
      other sites) with no parasites on the gills. Burrishoole (Ireland) differed by
      the absence of A. crassus and high prevalence of A. clavula (84%) but without
      consequences on BC. Gudenaa (Denmark), Corrib (Ireland), and Fremur (France) were
      close due to high prevalence of A. crassus (89-93%). Gudenaa and Corrib were the
      most similar because Pseudodactylogyrus sp. was also highly prevalent
      (respectively 71% and 60%) whereas absent in Fremur. Our results suggest that the
      fitness loss induced by the introduced parasites could affect the spawning
      success of migrant silver eels from Gudenaa and Corrib, and to a lesser extent
      from Fremur, but probably not those from Stockholm Archipelago and Burrishoole. 

PMID- 24135273
TI  - Is increased joint loading detrimental to obese patients with knee
      osteoarthritis? A secondary data analysis from a randomized trial.
AB  - OBJECTIVE: To investigate whether increased knee joint loading due to improved
      ambulatory function and walking speed following weight loss achieved over 16
      weeks accelerates symptomatic and structural disease progression over a
      subsequent 1 year weight maintenance period in an obese population with knee
      osteoarthritis (OA). METHODS: Data from a prospective study of weight loss in
      obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT)
      study) were used to determine changes in knee joint compressive loadings (model
      estimated) during walking after a successful 16 week weight loss intervention.
      The participants were divided into 'Unloaders' (participants that reduced joint
      loads) and 'Loaders' (participants that increased joint loads). The primary
      symptomatic outcome was changes in knee symptoms, measured with the Knee injury
      and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52
      weeks weight maintenance period. The primary structural outcome was changes in
      tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee
      Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period.
      RESULTS: 157 participants (82% of the CAROT cohort) with medial and/or lateral
      knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups
      showed similar significant changes in symptoms (group difference: -2.4 KOOS
      points [95% CI -6.8:1.9]) and cartilage loss (group difference: -0.06 BLOKS
      points [95% CI -0.22:0.11) after 1 year, with no statistically significant
      differences between Loaders and Unloaders. CONCLUSION: For obese patients
      undergoing a significant weight loss, increased knee joint loading for 1 year was
      not associated with accelerated symptomatic and structural disease progression
      compared to a similar weight loss group that had reduced ambulatory compressive
      knee joint loads. CLINICALTRIALSGOV: NCT00655941.

PMID- 24135274
TI  - Impact of concomitant cardiac procedures performed during implantation of long
      term left ventricular assist devices.
AB  - BACKGROUND: There is a paucity of data evaluating the effect of performing a
      concomitant cardiac procedure (CCP) on peri-operative survival in patients
      undergoing implantation of long-term left ventricular assist devices (LVADs). The
      objective of this study was to review our single-institutional experience with
      patients who underwent a CCP during implantation of a long-term continuous-flow
      LVAD. METHODS: From March 2006 through June 2012, 130 patients underwent
      implantation of a LVAD. Of these, 76 (58.5%) were implanted as bridge-to
      transplant and 54 (41.5%) as destination therapy. The LVAD implantation was
      isolated in 95 patients and with CCP in 35. This included 19 tricuspid valve
      repairs, 14 aortic valve repair/replacements, and 2 patent foramen ovale
      closures. The LVAD only and LVAD+CCP groups were compared regarding pre-operative
      demographics, peri-operative and midterm survival, and the incidence of post
      operative complications. RESULTS: Pre-operative central venous pressure (p =
      0.047), moderate to severe tricuspid regurgitation (p = 0.011), cardiopulmonary
      bypass time (p < 0.0001), cross-clamp time (p < 0.0001), and right ventricular
      end diastolic diameter (p = 0.039) were higher in the CCP group. Body mass index
      (p = 0.01) and body surface area (p = 0.037) were higher in the LVAD-only group.
      Peri-operative and midterm survival at 30 days, 6 months, 1 year, and 2 years was
      94%, 87%, 80%, and 73%, respectively, for isolated LVAD implants vs. 97%, 90%,
      86%, and 86%, respectively, for LVAD+CCP (p = NS). Survival was similar for LVAD
      patients with tricuspid valve repairs, with aortic valve repair, and with patent
      foramen ovale repair (p = NS). Cox proportional hazard models showed a CCP was
      not an independent predictor of outcome (p = NS). CONCLUSIONS: CCPs performed
      during implantation of a long-term continuous-flow LVADs does not increase peri
      operative or mid-term mortality. In addition, unlike previous reports, there was
      no additive procedural risk for patients undergoing concomitant aortic valve
      repair or replacement.

PMID- 24135275
TI  - NF-kappaB: a coordinator for epigenetic regulation by MLL.
AB  - NF-kappaB is involved in a variety of biological processes, including cancer
      development. In this issue of Cancer Cell, Kuo et al. show the essential role for
      IKK/NF-kappaB signaling in epigenetic regulation by MLL oncoproteins to maintain
      leukemia stem cells. 

PMID- 24135276
TI  - EGFR and EGFRvIII in glioblastoma: partners in crime.
AB  - EGFRvIII, a mutated form of EGFR, plays a prominent role in tumorigenesis, but
      the underlying mechanisms have remained elusive. In this issue of Cancer Cell,
      Weiss and colleagues implicate phosphorylation of EGFRvIII by EGFR and the
      consequent phosphorylation of STAT3 as a signaling axis that drives
      transformation in glioblastoma. 

PMID- 24135277
TI  - Wiping DNA methylation: Wip1 regulates genomic fluidity on cancer.
AB  - Wip1 phosphatase plays an important role in cancer by inactivating p53 and
      INK4a/ARF pathways. In this issue of Cancer Cell, Filipponi and colleagues
      further connect the oncogenic role of Wip1 with heterochromatin dynamics,
      transposable element expression, and a mutation-prone environment that may
      enhance heterogeneity and ultimately contribute to tumor evolution. 

PMID- 24135278
TI  - Cancer-associated osteoclast differentiation takes a good look in the miR(NA)ror.
AB  - Tumor-bone cell interactions are critical for the development of metastasis
      related osteolytic bone destruction. In this issue of Cancer Cell, Ell and
      colleagues show how a discrete miRNA network regulates osteoclastogenesis during
      breast cancer bone metastasis. A signature of upregulated miRNAs may have
      diagnostic and therapeutic implications for bone metastases. 

PMID- 24135279
TI  - Origins of metastatic traits.
AB  - How cancer cells acquire the competence to colonize distant organs remains a
      central question in cancer biology. Tumors can release large numbers of cancer
      cells into the circulation, but only a small proportion of these cells survive on
      infiltrating distant organs and even fewer form clinically meaningful metastases.
      During the past decade, many predictive gene signatures and specific mediators of
      metastasis have been identified, yet how cancer cells acquire these traits has
      remained obscure. Recent experimental work and high-resolution sequencing of
      human tissues have started to reveal the molecular and tumor evolutionary
      principles that underlie the emergence of metastatic traits. 

PMID- 24135280
TI  - EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in
      glioblastoma.
AB  - EGFRvIII, a frequently occurring mutation in primary glioblastoma, results in a
      protein product that cannot bind ligand, but signals constitutively. Deducing how
      EGFRvIII causes transformation has been difficult because of autocrine and
      paracrine loops triggered by EGFRvIII alone or in heterodimers with wild-type
      EGFR. Here, we document coexpression of EGFR and EGFRvIII in primary human
      glioblastoma that drives transformation and tumorigenesis in a cell-intrinsic
      manner. We demonstrate enhancement of downstream STAT signaling triggered by EGFR
      catalyzed phosphorylation of EGFRvIII, implicating EGFRvIII as a substrate for
      EGFR. Subsequent phosphorylation of STAT3 requires nuclear entry of EGFRvIII and
      formation of an EGFRvIII-STAT3 nuclear complex. Our findings clarify specific
      oncogenic signaling relationships between EGFR and EGFRvIII in glioblastoma. 

PMID- 24135282
TI  - DNp73 exerts function in metastasis initiation by disconnecting the inhibitory
      role of EPLIN on IGF1R-AKT/STAT3 signaling.
AB  - Dissemination of cancer cells from primary tumors is the key event in metastasis,
      but specific determinants are widely unknown. Here, we show that DNp73, an
      inhibitor of the p53 tumor suppressor family, drives migration and invasion of
      nonmetastatic melanoma cells. Knockdown of endogenous DNp73 reduces this behavior
      in highly metastatic cell lines. Tumor xenografts expressing DNp73 show a higher
      ability to invade and metastasize, while growth remains unaffected. DNp73
      facilitates an EMT-like phenotype with loss of E-cadherin and Slug upregulation.
      We provide mechanistic insight toward regulation of LIMA1/EPLIN by p73/DNp73 and
      demonstrate a direct link between the DNp73-EPLIN axis and IGF1R-AKT/STAT3
      activation. These findings establish initiation of the invasion-metastasis
      cascade via EPLIN-dependent IGF1R regulation as major activity of DNp73. 

PMID- 24135281
TI  - The role of Cdk5 in neuroendocrine thyroid cancer.
AB  - Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from
      calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its
      cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity
      promotes MTC proliferation. A conditional MTC mouse model was generated and
      corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific
      overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC,
      which was arrested by repressing p25 overexpression. A comparative
      phosphoproteomic screen between proliferating and arrested MTC identified the
      retinoblastoma protein (Rb) as a crucial Cdk5 downstream target. Prevention of Rb
      phosphorylation at Ser807/Ser811 attenuated MTC proliferation. These findings
      implicate Cdk5 signaling via Rb as critical to MTC tumorigenesis and progression.

PMID- 24135283
TI  - Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA
      methylation.
AB  - Wip1 phosphatase is emerging as an important regulator of tumorigenesis, but no
      unifying mechanistic network has been proposed. We found that Wip1 plays a key
      role in the transcriptional regulation of heterochromatin-associated DNA
      sequences. Wip1 was required for epigenetic remodeling of repetitive DNA elements
      through regulation of BRCA1 interaction with HP1, the recruitment of DNA
      methyltransferases, and subsequent DNA methylation. Attenuation of ATM, in turn,
      reversed heterochromatin methylation. This mechanism was critical for the
      recruitment of the AID cytidine deaminase, and Wip1 levels strongly correlated
      with C-to-T substitutions and a total mutation load in primary breast cancers. We
      propose that Wip1 plays an important role in the regulation of global
      heterochromatin silencing and thus is critical in maintaining genome integrity. 

PMID- 24135285
TI  - Peri-operative management in urinary diversion surgery: A time for change?
AB  - INTRODUCTION: Bowel preparation was established as part of the pre-operative
      course for patients undergoing ileal conduit formation since the late 1970's.
      Rationales for its use include reduction in infection and wound complications,
      technically easier anastomosis and earlier return to bowel function. However,
      recent reports have challenged this practice. Traditionally antibiotics were also
      administered for several days prior to surgery with the assumption that bacterial
      load was reduced. Modification of antibiotic protocols resulted from evidence
      based findings. Furthermore, publications emphasizing the benefit of Enhanced
      Recovery Protocols/Programmes (ERP) have become contemporary. METHODS: An online
      multiple-choice questionnaire (via Monkey Survey) was administered to all
      consultant urologists in Ireland. This national cross-sectional study evaluated
      the use of bowel preparation and antibiotic prophylaxis prior to urinary
      diversion. In addition, we also assessed consultant urologists' awareness of ERP
      and their views on the introduction and implementation of such a national
      program. RESULTS: Of the 41 consultant urologists surveyed, 80.4% (n = 33)
      responded. 63.6% routinely used bowel preparation. Klean Prep was the most
      commonly used bowel preparation. 80.9% of urologists admit their patient's one
      day pre-operatively for bowel preparation, with 87.8% using antibiotic
      prophylaxis at anesthesia induction, and 18.1% continuing the antibiotics for 24
      48 h post-operatively. Although 74% of consultants are aware of ERP, only 66.6%
      are in favor of their national implementation. CONCLUSION: The majority of Irish
      urologists use bowel preparation prior to ileal conduit formation. Substantial
      recent evidence has emerged showing no difference in infective complications or
      anastomotic leakage when bowel preparation was not used. National guidelines
      would be beneficial regarding the use of bowel preparation, antibiotic
      prophylaxis and ERP for urinary diversion surgery.

PMID- 24135286
TI  - [Aesthetic reconstructive surgery of the lip].
AB  - Lip reconstruction can be performed with numerous surgical techniques. The aim
      was here to present these usual techniques and to focus on the details that can
      be used to obtain the most favourable results. The goal of this surgery, that
      represents a compromise between function and aesthetic, has to be kept in mind to
      prevent mistakes that decrease the quality of the result. 

PMID- 24135284
TI  - Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic
      bone metastasis.
AB  - Understanding the mechanism by which tumor cells influence osteoclast
      differentiation is crucial for improving treatment of osteolytic metastasis.
      Here, we report broad microRNA (miRNA) expression changes in differentiating
      osteoclasts after exposure to tumor-conditioned media, in part through activation
      of NFkappaB signaling by soluble intracellular adhesion molecule (sICAM1)
      secreted from bone-metastatic cancer cells. Ectopic expression of multiple miRNAs
      downregulated during osteoclastogenesis suppresses osteoclast differentiation by
      targeting important osteoclast genes. Intravenous delivery of these miRNAs in
      vivo inhibits osteoclast activity and reduces osteolytic bone metastasis.
      Importantly, serum levels of sICAM1 and two osteoclast miRNAs, miR-16 and miR
      378, which are elevated in osteoclast differentiation, correlate with bone
      metastasis burden. These findings establish miRNAs as potential therapeutic
      targets and clinical biomarkers of bone metastasis.

PMID- 24135287
TI  - The role of chaplains in end-of-life decision making: results of a pilot survey.
AB  - OBJECTIVE: The overall aim of this study was to discover how chaplains assess
      their role within ethically complex end-of-life decisions. METHODS: A
      questionnaire was sent to 256 chaplains working for German health care
      institutions. Questions about their role and satisfaction as well as demographic
      data were collected, which included information about the chaplains' integration
      within multi-professional teams. RESULTS: The response rate was 59%, 141
      questionnaires were analyzed. Respondents reported being confronted with
      decisions concerning the limitation of life-sustaining treatment on average two
      to three times per month. Nearly 74% were satisfied with the decisions made
      within these situations. However, only 48% were satisfied with the communication
      process. Whenever chaplains were integrated within a multi-professional team
      there was a significantly higher satisfaction with both: the decisions made (p =
      0.000) and the communication process (p = 0.000). Significance of the results:
      Although the results of this study show a relatively high satisfaction among
      surveyed chaplains with regard to the outcome of decisions, one of the major
      problems seems to reside in the communication process. A clear integration of
      chaplains within multi-professional teams (such as palliative care teams) appears
      to increase the satisfaction with the communication in ethically critical
      situations.

PMID- 24135288
TI  - Arguments for a neuroorthopaedic strategy in upper limb arthrogryposis.
AB  - We present two children with a diagnosis of upper limb arthrogryposis and report
      on findings about brachial plexus exploration and a nerve transfer procedure to
      reanimate elbow flexion. Although the etiology of arthrogryposis multiplex
      congenita remains unknown and multifactorial, it can be worthful to explore the
      brachial plexus in the affected upper limb and to perform selective motor nerve
      transfers on morphologically well developed but not sufficiently innervated
      target muscles, like the biceps brachialis, brachialis, deltoid and supra
      /infraspinatus muscles. This strategy may reduce the necessity of later muscle
      transfers and improves the overall functional status of the affected limb(s). 

PMID- 24135289
TI  - Patient-reported outcome of solifenacin treatment among women experiencing
      urinary urgency and urgency incontinence.
AB  - OBJECTIVE: To evaluate treatment success and tolerability of solifenacin among
      women with urinary urgency (UU) and urgency urinary incontinence (UUI). METHODS:
      In a prospective, observational, multicenter pilot study in Slovenia and Croatia,
      100 women with UU and UUI were enrolled between January 2011 and July 2011.
      Patients received 5mg of solifenacin once daily for 12 weeks and completed a 3
      day bladder diary, urgency questionnaire, Urogenital Distress Inventory (UDI),
      and Incontinence Impact Questionnaire (IIQ). RESULTS: Overall, 91 women completed
      12 weeks of treatment. Severity, frequency, and bother of UU significantly had
      decreased at weeks 4 and 12 (P<0.001). Improvement in UU led to an improvement in
      mean IIQ score: a reduction in UU frequency had the greatest impact (P=0.006).
      The mean treatment success rate was 74.2% (by visual analog score) and was
      closely related to the mean change in irritative UDI score (r=0.39; P<0.001).
      Treatment success was greatest for patient perception of intensity of urgency
      scale (PPIUS; P=0.003), UU bother (P=0.017), and micturition frequency (P<0.026).
      Dry mouth occurred in 35.2% of women at 4 weeks, and 27.7% at week 12.
      CONCLUSION: Solifenacin treatment was effective and well-tolerated among women
      with UU and UUI. All overactive bladder symptoms had improved by week 12.

PMID- 24135290
TI  - Maternal and perinatal outcomes among women with eclampsia admitted to a tertiary
      care hospital in Hyderabad, Pakistan.

PMID- 24135291
TI  - Efficacy of mifepristone for cervical priming for second-trimester surgical
      termination of pregnancy.
AB  - OBJECTIVE: To determine whether mifepristone plus misoprostol was as effective as
      misoprostol with or without laminaria (depending on gestational age) for cervical
      preparation for second-trimester termination of pregnancy. METHODS: A
      retrospective cohort study was carried out among women who underwent surgical
      termination between 14 and 19+6 weeks of pregnancy. Those who received
      preoperative mifepristone were compared with those who did not. The study group
      received mifepristone plus misoprostol before dilation and evacuation of the
      uterus between May 2008 and September 2011. The comparison (non-mifepristone)
      group received misoprostol with or without laminaria between January 2005 and
      April 2008. RESULTS: There was no difference between the groups in terms of
      difficulty of cervical dilation, with an overall relative risk for moderate
      difficult dilation in the mifepristone group of 0.91 (95% confidence interval,
      0.49-1.68). There was no difference between the groups with regard to
      complications arising from the procedure. CONCLUSION: Mifepristone is effective
      for cervical priming prior to second-trimester dilation and evacuation in both
      multiparous and primiparous women, without an increase in complication rates.

PMID- 24135292
TI  - Perceptions of an open visitation policy by intensive care unit workers.
AB  - BACKGROUND: An intensive care unit (ICU) admission is a stressful event for the
      patient and the patient's family. Several studies demonstrated symptoms of
      anxiety, depression, and posttraumatic stress disorder in family members of
      patients admitted to ICU. Some studies recognize that the open visitation policy
      (OVP) is related to a reduction in symptoms of anxiety and depression for the
      patient and an improvement in family satisfaction. However, some issues have been
      presented as barriers for the adoption of that strategy. This study was designed
      to evaluate perceptions of physicians, nurses, and respiratory therapists (RTs)
      of an OVP and to quantify visiting times in a Brazilian private intensive care
      unit (ICU). METHODS: This observational and descriptive study was performed in
      the medical-surgical (22 beds) and neurologic ICU (8 beds) of Sirio-Libanes
      Hospital (HSL), Sao Paulo, Brazil. All physicians, nurses, and RTs from ICU were
      invited to participate in the study. A questionnaire was applied to all ICU
      workers who accepted to participate in the study. The questionnaire consisted of
      22 questions about the visiting policy. During five consecutive days, we
      evaluated the time that the visitors stayed in the patient room, as well as the
      type of visitor. RESULTS: A total of 106 ICU workers participated in this study
      (42 physicians, 39 nurses, and 25 RTs). Only three of the questions exposed a
      negative perception of the visiting policy: 53.3% of the participants do not
      think that the OVP consistently increases family satisfaction with patient's
      care; 59.4% of ICU workers think that the OVP impairs the organization of the
      patient's care; 72.7% of participants believe that their work suffers more
      interruptions because of the OVP. The median visiting time per day was 11.5
      hours. CONCLUSIONS: According to physicians, nurses, and respiratory therapists,
      the greatest impact of OVP is the benefit to the patients rather than to the
      family or to the staff. Furthermore, they feel that they need communication
      training to better interact with family members who are present in the ICU 24
      hours per day.

PMID- 24135293
TI  - Whole transcriptome analysis of the poultry red mite Dermanyssus gallinae (De
      Geer, 1778).
AB  - SUMMARY Although the poultry red mite Dermanyssus gallinae (De Geer, 1778) is the
      major parasitic pest in poultry farming causing substantial economic losses every
      year, nucleotide data are rare in the public databases. Therefore, de novo
      sequencing covering the transcriptome of D. gallinae was carried out resulting in
      a dataset of 232 097 singletons and 42 130 contiguous sequences (contigs) which
      were subsequently clustered into 24 140 isogroups consisting of 35 788 isotigs.
      After removal of sequences possibly originating from bacteria or the chicken
      host, 267 464 sequences (231 657 singletons, 56 contigs and 35 751 isotigs)
      remained, of which 10.3% showed homology to proteins derived from other
      organisms. The most significant Blast top-hit species was the mite Metaseiulus
      occidentalis followed by the tick Ixodes scapularis. To gain functional knowledge
      of D. gallinae transcripts, sequences were mapped to Gene Ontology terms, Kyoto
      Encyclopedia of Gene and Genomes (KEGG) pathways and parsed to InterProScan. The
      transcriptome dataset provides new insights in general mite genetics and lays a
      foundation for future studies on stage-specific transcriptomics as well as
      genomic, proteomic, and metabolomic explorations and might provide new
      perspectives to control this parasitic mite by identifying possible drug targets
      or vaccine candidates. It is also worth noting that in different tested species
      of the class Arachnida no 28S rRNA was detectable in the rRNA profile, indicating
      that 28S rRNA might consists of two separate, hydrogen-bonded fragments, whose
      (heat-induced) disruption may led to co-migration with 18S rRNA. 

PMID- 24135294
TI  - Clinical risk factors related to failures with zirconia-based restorations: an up
      to 9-year retrospective study.
AB  - OBJECTIVES: The first objective of this study was to retrospectively evaluate
      zirconia-based restorations (ZBR). The second was to correlate failures with
      clinical parameters and to identify and to analyse chipping failures using
      fractographic analysis. METHODS: 147 ZBR (tooth- and implant-supported crowns and
      fixed partial dentures (FPDs)) were evaluated after a mean observation period of
      41.5 +/- 31.8 months. Accessorily, zirconia implant abutments (n=46) were also
      observed. The technical (USPHS criteria) and the biological outcomes of the ZBR
      were evaluated. Occlusal risk factors were examined: occlusal relationships,
      parafunctional habits, and the presence of occlusal nightguard. SEM fractographic
      analysis was performed using the intra-oral replica technique. RESULTS: The
      survival rate of crowns and FPDs was 93.2%, the success rate was 81.63% and the 9
      year Kaplan-Meier estimated success rate was 52.66%. The chipping rate was 15%
      and the framework fracture rate was 2.7%. Most fractographic analyses revealed
      that veneer fractures originated from occlusal surface roughness. Several
      parameters were shown to significantly influence veneer fracture: the absence of
      occlusal nightguard (p=0.0048), the presence of a ceramic restoration as an
      antagonist (p=0.013), the presence of parafunctional activity (p=0.018), and the
      presence of implants as support (p=0.026). The implant abutments success rate was
      100%. CONCLUSIONS: The results of the present study confirm that chipping is the
      first cause of ZBR failure. They also underline the importance of clinical
      parameters in regards to the explanation of this complex problem. This issue
      should be considered in future prospective clinical studies. CLINICAL
      SIGNIFICANCE: Practitioners can reduce chipping failures by taking into account
      several risk parameters, such as the presence of a ceramic restoration as an
      antagonist, the presence of parafunctional activity and the presence of implants
      as support. The use of an occlusal nightguard can also decrease failure rate.

PMID- 24135296
TI  - Sterile paper points as a bacterial DNA-contamination source in microbiome
      profiles of clinical samples.
AB  - OBJECTIVES: High throughput sequencing of bacterial DNA from clinical samples
      provides untargeted, open-ended information on the entire microbial community.
      The downside of this approach is the vulnerability to DNA contamination from
      other sources than the clinical sample. Here we describe contamination from
      sterile paper points (PPs) used in microbial sample collection. METHODS: Peri
      implant samples from 48 individuals were collected using sterile PPs. Control
      samples contained only PPs or DNA extraction blank controls. 16S rRNA gene
      libraries were sequenced using 454 pyrosequencing. 16S rRNA gene copy numbers
      were measured by quantitative PCR. RESULTS: Nearly half of the sequencing reads
      belonged to two OTUs classified as Enterococcus (25% of reads) or Exiguobacterium
      (21%), which are not typical oral microorganisms. Of 87 peri-implant samples,
      only 10 samples (11%) contained neither of the two OTUs. The relative abundance
      of both unusual OTUs correlated with each other (p<0.001; r=0.828, Spearman
      correlation). The control samples showed that 2 of 4 (50%) of the sterile unused
      PPs contained bacterial DNA equivalent to 1.2 * 10(3) and 1.1 * 10(4) cells
      respectively, which was within the range of DNA in the clinical samples (average
      1.8 * 10(7), SD 4.8 * 10(7), min 4.4 * 10(2), max 2.8 * 10(8)). The microbial
      profile from these PPs was dominated (>83% of reads) by the two unusual OTUs.
      CONCLUSIONS: Sterile PPs can contain contaminating bacterial DNA. The use of PPs
      as a sampling tool for microbial profiling of clinical samples by open-ended
      techniques such as sequencing or DGGE should be avoided. CLINICAL SIGNIFICANCE:
      Clinicians working with PPs as sampling tools for bacterial DNA should consider
      using an alternative sampling tool, because sterile unused PPs can be a
      considerable source of foreign bacterial DNA. We recommend sterile curettes for
      collecting clinical samples for open-ended techniques, such as sequencing or
      DGGE.

PMID- 24135295
TI  - Fatigue of dental ceramics.
AB  - OBJECTIVES: Clinical data on survival rates reveal that all-ceramic dental
      prostheses are susceptible to fracture from repetitive occlusal loading. The
      objective of this review is to examine the underlying mechanisms of fatigue in
      current and future dental ceramics. DATA/SOURCES: The nature of various fatigue
      modes is elucidated using fracture test data on ceramic layer specimens from the
      dental and biomechanics literature. CONCLUSIONS: Failure modes can change over a
      lifetime, depending on restoration geometry, loading conditions and material
      properties. Modes that operate in single-cycle loading may be dominated by
      alternative modes in multi-cycle loading. While post-mortem examination of failed
      prostheses can determine the sources of certain fractures, the evolution of these
      fractures en route to failure remains poorly understood. Whereas it is commonly
      held that loss of load-bearing capacity of dental ceramics in repetitive loading
      is attributable to chemically assisted 'slow crack growth' in the presence of
      water, we demonstrate the existence of more deleterious fatigue mechanisms,
      mechanical rather than chemical in nature. Neglecting to account for mechanical
      fatigue can lead to gross overestimates in predicted survival rates. CLINICAL
      SIGNIFICANCE: Strategies for prolonging the clinical lifetimes of ceramic
      restorations are proposed based on a crack-containment philosophy.

PMID- 24135297
TI  - Bilateral acute pyogenic conjunctivitis with iritis induced by unilateral topical
      application of bacterial peptidoglycan muramyl dipeptide in adult rabbits.
AB  - The factors responsible for the conjunctivitis and iritis associated with acute
      ocular infection and post enteric inflammatory disease are not fully known. The
      pro-inflammatory activity of unilateral topical application of muramyl dipeptide
      (MDP; the smallest bio-active Gram-positive and Gram-negative bacterial cell wall
      component) was investigated in adult rabbits. The resultant bilateral
      conjunctivitis/iritis and pyogenic responses were characterized. Bilateral
      symptoms were graded by slit lamp examinations; tear fluid, Schirmer tests (tear
      production), blood and aqueous humor (AH) samples were obtained from MDP-treated
      and untreated rabbits. MDP concentration, gamma-glutamyltranspeptidase activity
      (GGT; key enzyme in glutathione recapture, xenobiotic detoxification, eicosanoid
      synthesis and neutrophil function), protein concentration, and tear cell density,
      cytology, and immunofluorescent antibody reactivity to GGT and calreticulin (CRT;
      MDP-binding protein) were determined. MDP was cleared from ipsilateral tears and
      serum by 6 h, but was undetected in mock-treated contralateral tears. Bilateral
      signs of acute transient pyogenic conjunctivitis, characterized by tearing, lid
      edema, conjunctival hyperemia, chemosis and leukocytic infiltrate with iritis
      (erythema and aqueous flare) were detected. Milder symptoms occurred in the mock
      treated contralateral eyes. Bilateral symptoms, tear production, tear protein,
      GGT activity, and mucopurulent discharge (containing up to 2.5-5.0 * 10(6)
      cells/mL) were elevated 4-8 h post MDP and resolved to near pre-treatment levels
      by 24 h. Tear GGT activity and protein levels were higher in MDP-treated and mock
      treated contralateral eyes than in eyes of untreated adult rabbits (p's < 0.001).
      Elevated tear GGT activity was associated with histopathology and increased
      vascular and epithelial permeability to serum protein, GGT-positive epithelia
      cells, macrophages and heterophils. Repeat MDP applications induced recurrent
      induction and resolution patterns of bilateral conjunctivitis/iritis and tear GGT
      activity, but ipsilateral GGT responses were lower. The results suggest
      unilateral topical MDP application to adult rabbit eyes induces a bilateral acute
      pyogenic conjunctivitis/iritis (PCI) characterized by increased vascular and
      epithelial permeability similar to acute bacterial conjunctivitis in man. The
      detection of CRT/GGT positive heterophils in tears suggests efferocytosis
      (phagocytosis of dead/dying cells). Tear GGT activity may be a useful means to
      quantify MDP-induced toxicity and extraocular inflammation. 

PMID- 24135298
TI  - Functional significance of thermosensitive transient receptor potential
      melastatin channel 8 (TRPM8) expression in immortalized human corneal endothelial
      cells.
AB  - Human corneal endothelial cells (HCEC) maintain appropriate tissue hydration and
      transparency by eliciting net ion transport coupled to fluid egress from the
      stroma into the anterior chamber. Such activity offsets tissue swelling caused by
      stromal imbibition of fluid. As corneal endothelial (HCE) transport function is
      modulated by temperature changes, we probed for thermosensitive transient
      receptor potential melastatin 8 (TRPM8) functional activity in immortalized human
      corneal endothelial cells (HCEC-12) and freshly isolated human corneal
      endothelial cells (HCEC) as a control. This channel is either activated upon
      lowering to 28  degrees C or by menthol, eucalyptol and icilin. RT-PCR and
      quantitative real-time PCR (qPCR) verified TRPM8 gene expression. Ca(2+)
      transients induced by either menthol (500 MUmol/l), eucalyptol (3 mmol/l), or
      icilin (2-60 MUmol/l) were identified using cell fluorescence imaging. The TRP
      channel blocker lanthanum III chloride (La(3+), 100 MUmol/l) as well as the TRPM8
      blockers BCTC (10 MUmol/l) and capsazepine (CPZ, 10 MUmol/l) suppressed icilin
      induced Ca(2+) increases. In and outward currents induced by application of
      menthol (500 MUmol/l) or icilin (50 MUmol/l) were detected using the planar patch
      clamp technique. A thermal transition from room temperature to ~ 18  degrees C
      led to Ca(2+) increases that were inhibited by a TRPM8 blocker BCTC (10 MUmol/l).
      Other thermosensitive TRP pathways whose heterogeneous Ca(2+) response patterns
      are suggestive of other Ca(2+) handling pathways were also detected upon strong
      cooling (~10  degrees C). Taken together, functional TRPM8 expression in HCEC-12
      and freshly dissociated HCEC suggests that HCE function can adapt to thermal
      variations through activation of this channel subtype. 

PMID- 24135299
TI  - Pupillary light reflex deficits in a canine model of late infantile neuronal
      ceroid lipofuscinosis.
AB  - Late-infantile neuronal ceroid lipofuscinosis (CLN2) is a hereditary neurological
      disorder characterized by progressive retinal degeneration and vision loss,
      cognitive and motor decline, seizures, and pronounced brain atrophy. The
      progressive loss of neurological functions eventually leads to death, usually by
      the early teenage years. Utilizing a canine model of CLN2, therapeutic studies to
      inhibit the brain and retinal degenerations are currently under way. Using this
      dog model, studies were undertaken to compare quantitative assessments of the
      pupillary light reflex (PLR) and electroretinography (ERG) as tools for
      evaluating the effects of the disease on retinal function. The PLR and ERG were
      recorded in normal and CLN2-affected Dachshunds at 2 month intervals between the
      ages of 4 and 10 months. Using custom instrumentation for quantitative PLR
      assessments, a series of white light stimuli of varying intensity was used to
      elicit pupil constriction, and pupil images were recorded using continuous
      infrared illumination and an infrared-sensitive camera. Electroretinography was
      used to evaluate retinal function in the same dogs. As the disease progressed,
      affected dogs exhibited progressive and profound declines in ERG amplitudes under
      both scotopic and photopic conditions. With low intensity light stimuli, CLN2 was
      also accompanied by progressive deficits in the PLR. Changes in the PLR to dim
      light stimuli included significant deficits in latency, constriction velocity,
      constriction amplitude, and redilation velocity. However, despite the almost
      complete loss of detectable ERG responses by disease end stage, the PLR to bright
      stimuli was well preserved throughout the disease progression. These findings
      demonstrate that the PLR is much more sensitive than the ERG in detecting
      residual retinal function in animal models of retinal degenerative disease. The
      preservation of the PLR in dogs with profoundly depressed ERGs correlates with a
      preservation of visually-mediated behavior even late in the disease progression.
      Quantitative analysis of the PLR has potential as a biomarker in animal models of
      retinal degenerative diseases and in evaluating the efficacy of therapeutic
      interventions in preserving retinal function. 

PMID- 24135300
TI  - Association between psoriasis and polymorphisms in the TNF, IL12B, and IL23R
      genes in Spanish patients.
AB  - BACKGROUND & OBJECTIVES: Susceptibility to psoriasis has been associated with the
      HLA-C*0602 allele, although it may be affected by other polymorphisms. MATERIALS
      & METHODS: We genotyped 142 patients and 160 healthy volunteers to evaluate the
      possible relationship between susceptibility to psoriasis and the HLA-C*0602
      allele and polymorphisms in the TNF, IL12B, and IL23R genes. RESULTS: The
      frequency of the wild-type TNF-238, TNF-308, and TNF-1031 genotypes was greater
      in patients with psoriasis than in healthy volunteers, although that of the
      mutant TNF-857 genotype was higher. The only difference between psoriasis and
      psoriatic arthritis was TNF-857. The frequency of the HLAC*0602 allele was higher
      in psoriatic patients than in healthy volunteers. No differences were observed
      for IL12B and IL23R. Multivariate logistic regression analysis only confirmed
      these associations for TNF-238, TNF-857, and HLA-C*0602. CONCLUSION: Our results
      support an association between susceptibility to psoriasis and TNF polymorphisms
      in the Spanish population.

PMID- 24135301
TI  - New-onset atrial fibrillation after acute myocardial infarction and its relation
      to admission biomarkers (from the TRIUMPH registry).
AB  - Atrial fibrillation (AF) is an independent predictor of mortality after acute
      myocardial infarction (AMI). We analyzed the relation between biomarkers linked
      to myocardial stretch (NT-pro-brain natriuretic peptide [NT-proBNP]), myocardial
      damage (Troponin-T [TnT]), and inflammation (high-sensitivity C-reactive protein
      [hs-CRP]) and new-onset AF during AMI to identify patients at high risk for AF.
      In a prospective multicenter registry of AMI patients (from the Translational
      Research Investigating Underlying disparities in recovery from acute Myocardial
      infarction: Patients' Health status registry), we measured NT-proBNP, TnT, and hs
      CRP in patients without a history of AF (n = 2,370). New-onset AF was defined as
      AF that occurred during the index hospitalization. Hierarchical multivariate
      logistic regression models were used to determine the association of biomarkers
      with new-onset AF, after adjusting for other covariates. New-onset AF was
      documented in 114 patients with AMI (4.8%; mean age 58 years; 32% women). For
      each twofold increase in NT-proBNP, there was an 18% increase in the rate of AF
      (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03 to 1.35; p <0.02).
      Similarly, for every twofold increase in hs-CRP, there was a 15% increase in the
      rate of AF (OR 1.15, 95% CI 1.02 to 1.30; p = 0.02). TnT was not independently
      associated with new-onset AF (OR 0.96, 95% CI 0.85 to 1.07; p = 0.3). NT-proBNP
      and hs-CRP were independently associated with new in-hospital AF after MI, in
      both men and women, irrespective of race. Our study suggests that markers of
      myocardial stretch and inflammation, but not the amount of myocardial necrosis,
      are important determinants of AF in the setting of AMI.

PMID- 24135302
TI  - Long-term effect of continuing sports activity in competitive athletes with
      frequent ventricular premature complexes and apparently normal heart.
AB  - The long-term outcome of athletes with frequent ventricular premature complexes
      (VPCs) and apparently normal heart has not been fully clarified. To evaluate the
      clinical and prognostic significance of VPCs and the influence of continuing
      sports activity during follow-up, we studied 120 healthy athletes (96 men; median
      age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by
      chance during preparticipation screening. All athletes were followed up for a
      median of 84 months. During follow-up, 96 underwent serial 24-hour Holter
      recording and 62 underwent serial echocardiography. The median number of VPCs/24
      hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports
      activity, whereas 39 did not. No athlete died or developed overt heart disease.
      The median number of VPCs/24 hours decreased in both athletes who continued
      sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from
      5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular
      ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect
      to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs
      3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36
      months). In conclusion, (1) frequent VPCs in athletes without heart disease have
      a long-term benign prognostic significance, (2) sporting activity does not modify
      this benign outcome, (3) during follow-up, the burden of VPCs decreases whether
      or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection
      fraction slightly decreases over time.

PMID- 24135303
TI  - Renal artery stenosis in patients with resistant hypertension.
AB  - The aim of the study was to assess the significance of renal translesional
      pressure gradients in predicting improvement in resistant hypertension after
      stenting for moderate renal artery stenosis (RAS). In 37 patients with RAS and
      resistant hypertension subjected to renal stenting, translesional pressure
      gradients both at rest and hyperemic were measured using a pressure guidewire.
      Twenty-four-hour ambulatory blood pressure measurements were performed in all
      patients on admission and 3 months after the intervention. Angioplasty was
      successful in all patients, with reduction of artery diameter stenosis from 60 +/
      12% to 10 +/- 6% (p <0.0001). At 3 months, with maintained hypotensive agents
      (4.0 +/- 1.4 vs 4.0 +/- 1.6), significant reductions in systolic blood pressure
      (SBP) and diastolic blood pressure were noted (-5 and -2 mm Hg, respectively). In
      multivariate analysis, the mean baseline gradient (MBG) was the only independent
      predictor of improvement in SBP (regression coefficient 0.292; standard error
      0.11; p value 0.014). In the receiver operating characteristic curve analysis,
      MBG had a larger area under the curve than other parameters, and the MBG >22 mm
      Hg had the highest sensitivity, specificity, and accuracy (50%, 95%, and 0.74%,
      respectively) in predicting hypertension improvement after stenting. In patients
      with MBG >22 mm Hg, SBP decreased by 12 versus 3 mm Hg (p <0.01) in patients with
      MBG <=22 mm Hg, whereas diastolic blood pressure in both groups decreased by 3
      versus 1 mm Hg, respectively (NS). In conclusion, MBG value of >22 mm Hg provides
      the highest accuracy in predicting hypertension improvement after stenting for
      moderate RAS in patients with resistant hypertension.

PMID- 24135304
TI  - Lazar John Greenfield, MD: an interview with the editor.

PMID- 24135305
TI  - [Endovascular renal nerve ablation as a treatment for resistant hypertension].
AB  - Radiofrequency-induced renal ablation is a non-pharmacologic therapeutic approach
      for the treatment of essential resistant hypertension, with a stable blood
      pressure lowering effect. However, data from published studies cannot conclude
      yet on the long-term efficacy and safety of the procedure. Therefore, the various
      techniques of renal nerve ablation (radiofrequency, cryoablation, ultrasounds)
      need further evaluation in clinical research trials. According to recent national
      and international recommendations, renal ablation should be reserved for patients
      with essential resistant hypertension. 

PMID- 24135306
TI  - Relationship between changes in plasma leptin concentrations and plasminogen
      activator inhibitor-1 in obese prepubertal children after nine months of
      treatment.
AB  - BACKGROUND/AIMS: The metabolic syndrome (MS) is associated with insulin
      resistance (IR), inappropriate fibrinolysis and high plasma leptin
      concentrations. The aim of this study was to quantify fibrinolysis and MS-related
      variables in obese prepubertal children and to evaluate changes in these
      variables as a result of improved body mass index (BMI), IR and leptin levels
      following 9 months of treatment. METHODS: The homeostasis model assessment for
      insulin resistance (HOMA-IR), leptin, plasminogen activator inhibitor-1 (PAI-1)
      and lipid profile were studied at baseline in obese (n = 50) and nonobese
      children (n = 50), and after 9 months of treatment in obese children. RESULTS: In
      the cross-sectional study the mean values for insulin, HOMA-IR, triglycerides,
      leptin and PAI-1 were significantly higher in obese children than in controls.
      High-density lipoprotein cholesterol (HDLc) and apolipoprotein A-1 were
      significantly lower. In the longitudinal study, after 9 months, children with
      lowered BMI standard deviation score displayed a significant decrease in insulin,
      HOMA-IR, PAI-1, leptin and triglyceride levels, and an increase in HDLc. Only
      leptin proved to be an independent predictive factor for changes in PAI-1 (p =
      0.010). CONCLUSION: Obesity-linked disorders appear in obese children prior to
      puberty; these disorders can be improved by decreasing BMI. Changes in leptin
      levels were found to independently predict changes in PAI-1 in obese children and
      can help to diagnose complications associated with the obesity.

PMID- 24135307
TI  - Odors as effective retrieval cues for stressful episodes.
AB  - Olfactory information seems to play a special role in memory due to the fast and
      direct processing of olfactory information in limbic areas like the amygdala and
      the hippocampus. This has led to the assumption that odors can serve as effective
      retrieval cues for autobiographic memories, especially emotional memories. The
      current study sought to investigate whether an olfactory cue can serve as an
      effective retrieval cue for memories of a stressful episode. A total of 95
      participants were exposed to a psychosocial stressor or a well matching but not
      stressful control condition. During both conditions were visual objects present,
      either bound to the situation (central objects) or not (peripheral objects).
      Additionally, an ambient odor was present during both conditions. The next day,
      participants engaged in an unexpected object recognition task either under the
      influence of the same odor as was present during encoding (congruent odor) or
      another odor (non-congruent odor). Results show that stressed participants show a
      better memory for all objects and especially for central visual objects if
      recognition took place under influence of the congruent odor. An olfactory cue
      thus indeed seems to be an effective retrieval cue for stressful memories. 

PMID- 24135308
TI  - Invisible bleeding from clean-shave haircuts: detection with blood specific RNA
      markers.
AB  - BACKGROUND: 'Haircut-associated bleeding' is a newly recognized entity that
      affects at least a quarter of African men who wear shiny clean-shave ('chiskop')
      haircuts. AIM: This pilot study aimed to elucidate whether invisible haircut
      associated bleeding was detectable using blood specific RNA markers (16
      participants, 5 with unknown HIV status) and whether surface virus could be
      detected using PCR from scalp swabs (of 11 known HIV-positive participants).
      METHODS: Haircuts were performed professionally and scalps examined by a
      dermatologist to exclude injury. Serum samples for viral loads were also
      collected at the same time. RESULTS: In all, 6/16 (37%) samples tested positive
      (>100 relative fluorescent units) for hemoglobin beta and albumin, confirming
      evidence of blood; of these, only 1/11 was HIV-positive but had an undetectable
      serum viral load. No surface HIV was detected from any scalp samples.
      CONCLUSIONS: This study confirms the entity of haircut-associated bleeding but
      goes further to show for the first time that invisible bleeding from clean-shave
      haircuts is also common. Both a high serum viral load and evidence of bleeding
      should ideally be present prior to surface HIV detection. Future investigations
      for potential HIV (and hepatitis B) transmission through clean-shave haircuts are
      warranted but should not delay public education for disease prevention.

PMID- 24135309
TI  - Minimal residual disease-based risk stratification in acute myeloid leukemia.

PMID- 24135310
TI  - Infectious sacroiliitis caused by Staphylococcus aureus following acupuncture: a
      case report.
AB  - Determination of the origin of infectious sacroiliitis (ISI), a rare form of
      septic arthritis, is often time consuming and clinically difficult owing to its
      various presentations, which include joint, skin and urinary tract infections.
      This report describes the diagnosis, determination of infectious origin and
      treatment of a case of ISI attributed to the use of acupuncture for the treatment
      of lower back pain. We report on a 61-year-old man who developed right hip pain
      and fever 3 days after undergoing acupuncture over the right buttock region for
      the treatment of lower back pain. Blood culture showed infection with methicillin
      susceptible Staphylococcus aureus and MRI disclosed the presence of an inflamed
      area over the right iliac bone and the right portion of the sacrum. The patient
      was cured after a 4-week course of antimicrobial treatment. Clinicians should
      take a history of acupuncture use when evaluating patients presenting with fever
      of unknown origin and/or bacteraemia and consider the possibility of ISI when
      evaluating patients with hip pain and infectious signs after acupuncture or other
      possible causes of infection. This indicates the importance of performing
      clinically clean procedures to prevent septic complications when treating
      patients with acupuncture. 

PMID- 24135311
TI  - Social dynamics in rural Sri Lankan hospitals: revelations from self-poisoning
      cases.
AB  - Different hospitals produce different cultures-products of relationships between
      people of different staff categories and people from external community groups.
      These relationships demonstrate unique social dynamics in rural peripheral
      hospitals that form a major part of the health care system in Sri Lanka and other
      developing countries. Understanding the existing social dynamics might be useful
      when trying to implement new treatment guidelines that can involve behavior
      change. We aimed to explore the existing social dynamics in peripheral hospitals
      in rural Sri Lanka by examining the treatment related to cases of acute self
      poisoning that is a common, highly interactive medical emergency. These hospitals
      demonstrate higher levels of community influence in treatment decisions and
      closer interactions between hospital staff. We argue that health care teamwork is
      effective in peripheral hospitals, resulting in benefits to all staff, who see
      these hospitals as better places to work and train, in contrast to a commonly
      held belief that such rural hospitals are disadvantaged and difficult places. 

PMID- 24135312
TI  - Insight into Jordanian thinking about HIV: knowledge of Jordanian men and women
      about HIV prevention.
AB  - Research on HIV prevention programs for countries with large Muslim populations
      is scarce. HIV knowledge, attitudes, and beliefs were assessed in a convenience
      sample of 128 women and 88 men at two universities in Jordan with the goal of
      gaining insight into how to approach HIV risk behaviors. In general terms, 97% of
      participants had heard of AIDS and the majority understood the common methods of
      transmission. Misconceptions were common; most participants did not recognize
      condoms as an HIV prevention method. A sense of fatalism regarding the
      acquisition of HIV was common. In Jordan, challenges to HIV-prevention
      interventions includes misconceptions about HIV transmission, gender-related
      differences in the willingness to discuss sexual issues, and fatalism regarding
      the acquisition of HIV. Silence about sexual activity, particularly among women,
      was pervasive. Culturally tailored interventions are needed to decrease stigma
      and address gender inequalities that may contribute to increased risks of HIV in
      Jordan. 

PMID- 24135313
TI  - Number line estimation and mental addition: examining the potential roles of
      language and education.
AB  - This study investigated the relative importance of language and education to the
      development of numerical knowledge. Consistent with previous research suggesting
      that counting systems that transparently reflect the base-10 system facilitate an
      understanding of numerical concepts, Chinese and Chinese American kindergartners'
      and second graders' number line estimation (0-100 and 0-1000) was 1 to 2 years
      more advanced than that of American children tested in previous studies. However,
      Chinese children performed better than their Chinese American peers, who were
      fluent in Chinese but had been educated in America, at kindergarten on 0-100
      number lines, at second grade on 0-1000 number lines, and at both time points on
      complex addition problems. Overall, the pattern of findings suggests that
      educational approach may have a greater influence on numerical development than
      the linguistic structure of the counting system. The findings also demonstrate
      that, despite generating accurate estimates of numerical magnitude on 0-100
      number lines earlier, it still takes Chinese children approximately 2 years to
      demonstrate accurate estimates on 0-1000 number lines, which raises questions
      about how to promote the mapping of knowledge across numerical scales.

PMID- 24135314
TI  - Meaning of the terms "overweight" and "obese" among low-income women.
AB  - OBJECTIVE: To determine how low-income, US women understand the meanings of the
      terms "overweight" and "obese." METHODS: Low-income women (n = 145; 72% white,
      12% black, and 8% Hispanic; 59% obese and 21% overweight) each participated in an
      individual semi-structured interview during which they were asked to explain what
      the terms "overweight" and "obese" mean to them. Responses were transcribed and
      the constant comparative method was used to identify themes. RESULTS: Three
      themes emerged: (1) The terms are offensive and describe people who are
      unmotivated and depressed and do not care about themselves; (2) obese is an
      extreme weight (eg, 500 lb and being immobile); (3) being overweight is a matter
      of opinion; if a woman is "comfortable in her own skin" and "feels healthy," she
      is not overweight. CONCLUSIONS AND IMPLICATIONS: Health education focused on
      obesity should consider that vulnerable populations might consider the terms
      "overweight" and "obese" offensive and stigmatizing.

PMID- 24135315
TI  - Coping with the challenges of early disaster response: 24 years of field hospital
      experience after earthquakes.
AB  - OBJECTIVE: To propose strategies and recommendations for future planning and
      deployment of field hospitals after earthquakes by comparing the experience of 4
      field hospitals deployed by The Israel Defense Forces (IDF) Medical Corps in
      Armenia, Turkey, India and Haiti. METHODS: Quantitative data regarding the
      earthquakes were collected from published sources; data regarding hospital
      activity were collected from IDF records; and qualitative information was
      obtained from structured interviews with key figures involved in the missions.
      RESULTS: The hospitals started operating between 89 and 262 hours after the
      earthquakes. Their sizes ranged from 25 to 72 beds, and their personnel numbered
      between 34 and 100. The number of patients treated varied from 1111 to 2400. The
      proportion of earthquake-related diagnoses ranged from 28% to 67% (P < .001),
      with hospitalization rates between 3% and 66% (P < .001) and surgical rates from
      1% to 24% (P < .001). CONCLUSIONS: In spite of characteristic scenarios and
      injury patterns after earthquakes, patient caseload and treatment requirements
      varied widely. The variables affecting the patient profile most significantly
      were time until deployment, total number of injured, availability of adjacent
      medical facilities, and possibility of evacuation from the disaster area. When
      deploying a field hospital in the early phase after an earthquake, a wide
      variability in patient caseload should be anticipated. Customization is difficult
      due to the paucity of information. Therefore, early deployment necessitates full
      logistic self-sufficiency and operational versatility. Also, collaboration with
      local and international medical teams can greatly enhance treatment capabilities.

PMID- 24135316
TI  - Paenirhodobacter enshiensis gen. nov., sp. nov., a non-photosynthetic bacterium
      isolated from soil, and emended descriptions of the genera Rhodobacter and
      Haematobacter.
AB  - A Gram-reaction-negative, facultatively anaerobic, non-motile, rod-shaped, non
      photosynthetic bacterial strain, DW2-9(T), was isolated from soil. The highest
      16S rRNA gene sequence similarities were found to Rhodobacter capsulatus ATCC
      11166(T) (97.1%), Rhodobacter viridis JA737(T) (96.4%), Rhodobacter maris
      JA276(T) (96.2%), Rhodobacter veldkampii ATCC 35703(T) (96.0%), Haematobacter
      massiliensis CCUG 47968(T) (96.0%), Haematobacter missouriensis CCUG 52307(T)
      (95.9%) and Rhodobacter aestuarii JA296(T) (95.7%). The genomic DNA G+C content
      was 67.2 mol% and the major respiratory quinone was ubiquinone 10 (Q-10). The
      major cellular fatty acids (>5%) were C(18 : 1)omega7c, C(16 : 0), C(19 : 0)
      cyclo omega8c and summed feature 3 (one or more of iso-C(15 : 0) 2-OH, C(16 :
      1)omega6c and C(16 : 1)omega7c). However, unlike species of the genus
      Rhodobacter, strain DW2-9(T) neither formed internal photosynthetic membranes nor
      produced photosynthetic pigments. DNA-DNA hybridization between strain DW2-9(T)
      and R. capsulatus JCM 21090(T) showed a relatedness of 33%. Strain DW2-9(T)
      contained phosphatidylethanolamine, phosphatidylglycerol and an unknown
      aminophospholipid as major polar lipids, which differed from those of species of
      the genera Rhodobacter and Haematobacter. In addition to the differences in
      phylogenetic position and polar lipid types, strain DW2-9(T) could be
      distinguished from species of the genus Haematobacter by the cultivation
      conditions. On the basis of our polyphasic taxonomic analysis, strain DW2-9(T) is
      considered to represent a novel genus and species, for which the name
      Paenirhodobacter enshiensis gen. nov., sp. nov. is proposed. The type strain of
      Paenirhodobacter enshiensis is DW2-9(T) ( = CCTCC AB 2011145(T) = KCTC 15169(T)).
      Emended descriptions of the genera Rhodobacter and Haematobacter are also
      proposed.

PMID- 24135317
TI  - Vitellibacter soesokkakensis sp. nov., isolated from the junction between the
      ocean and a freshwater spring and emended description of the genus Vitellibacter.
AB  - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated, motile by
      gliding and rod-shaped bacterial strain, RSSK-12(T), was isolated from the zone
      where the ocean and a freshwater spring meet at Jeju island, South Korea. Strain
      RSSK-12(T) grew optimally at 30  degrees C, at pH 7.0-8.0 and in the presence of
      2.0-3.0% (w/v) NaCl. Neighbour-joining, maximum-likelihood and maximum-parsimony
      phylogenetic trees based on 16S rRNA gene sequences revealed that strain RSSK
      12(T) clustered with the type strains of two Vitellibacter species, with which it
      exhibited 94.8-96.9% sequence similarity. Sequence similarities to the type
      strains of species of the genus Aequorivita and of other recognized species were
      94.7-95.5% and less than 91.9%, respectively. Strain RSSK-12(T) contained MK-6 as
      the predominant menaquinone and iso-C(15 : 0) and iso-C17 : 0 3-OH as the major
      fatty acids. The major polar lipids of strain RSSK-12(T) were
      phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of
      strain RSSK-12(T) was 38.9 mol%. Differential phenotypic properties, together
      with phylogenetic distinctiveness, revealed that strain RSSK-12(T) is separate
      from other Vitellibacter species. On the basis of the data presented, strain RSSK
      12(T) is considered to represent a novel species of the genus Vitellibacter, for
      which the name Vitellibacter soesokkakensis sp. nov. is proposed. The type strain
      is RSSK-12(T) ( = KCTC 32536(T) = CECT 8398(T)).

PMID- 24135318
TI  - A co-invasive microsporidian parasite that reduces the predatory behaviour of its
      host Dikerogammarus villosus (Crustacea, Amphipoda).
AB  - Parasites are known to affect the predatory behaviour or diet of their hosts. In
      relation to biological invasions, parasites may significantly influence the
      invasiveness of the host population and/or mediate the relationships between the
      invader and the invaded community. Dikerogammarus villosus, a recently introduced
      species, has had a major impact in European rivers. Notably, its high position in
      trophic web and high predatory behaviour, have both facilitated its invasive
      success, and affected other macroinvertebrate taxa in colonized habitats. The
      intracellular parasite Cucumispora dikerogammari, specific to D. villosus, has
      successfully dispersed together with this amphipod. Data presented here have
      shown that D. villosus infected by this parasite have a reduced predatory
      behaviour compared with healthy individuals, and are much more active suggesting
      that the co-invasive parasite may diminish the predatory pressure of D. villosus
      on newly colonized communities.

PMID- 24135319
TI  - Expression profile of the aromatase enzyme in the Xenopus brain and localization
      of estradiol and estrogen receptors in each tissue.
AB  - Estradiol (E2) with the strongest bioactivity of the estrogens, is synthesized by
      the cytochrome p450 aromatase enzyme and plays a key role in sex differentiation
      of the vertebrate's gonads. In Xenopus, aromatase mRNA is highly expressed in the
      brain rather than in the gonad during sex differentiation. In this study, we
      analyzed the stage change, tissue specificity, and localization of the aromatase
      expression in the Xenopus brain. Regardless of the sex difference, expression
      level of aromatase was remarkably higher in the brain than in other tissues
      during the early stages of brain morphogenesis and was observed in the formation
      regions of the choroid plexus of cerebral ventricle and the paleocortex and
      olfactory bulb of the prosencephalon. However, E2 concentrations in each tissue
      indicated a different localization of aromatase and were seen in the heart at
      almost double the level as seen in the brain. In addition, while aromatase
      expression level in the brain was increasing, E2 in the whole body began to
      increase at the same stage. Since the expression level of estrogen receptor alpha
      also corresponded to localization of E2, these results may imply that the E2
      synthesized by the high aromatase expression in the choroid plexus, which
      generates cerebrospinal fluid, circulates to the heart and acts through ERalpha. 

PMID- 24135320
TI  - Is one better than two?: T1 mapping in myocarditis.

PMID- 24135321
TI  - CT assessment of coronary artery disease: trends and clinical implications.

PMID- 24135323
TI  - OCT versus IVUS: accuracy versus clinical utility.

PMID- 24135322
TI  - Relationship of serum inflammatory biomarkers with plaque inflammation assessed
      by FDG PET/CT: the dal-PLAQUE study.
AB  - OBJECTIVES: This study sought to longitudinally investigate the relationship
      between a broad spectrum of serum inflammatory biomarkers and plaque inflammation
      assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT). BACKGROUND: Both plaque inflammation and serum
      biomarkers of inflammation are associated with atherothrombotic events; however,
      the relationship between them is unclear. METHODS: We conducted a post hoc
      analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect
      of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients
      With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk
      Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl
      ester transfer protein inhibitor, in 130 patients with coronary heart disease, or
      coronary heart disease risk equivalents on stable lipid-lowering therapy.
      Baseline and change after 3-month follow-up in inflammatory biomarker levels and
      baseline and change after 3-month follow-up in aorta and carotid (18)F-FDG PET/CT
      (mean maximum target-to-background ratio of the most diseased segment [TBRmds])
      were analyzed. RESULTS: Baseline myeloperoxidase positively correlated with
      baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the
      3-month follow-up and was independent of traditional cardiovascular disease risk
      factors. Baseline lipoprotein-associated phospholipase A2 mass correlated with
      aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the
      3-month follow-up and was not independent of cardiovascular disease risk factors.
      There was no association between change from baseline in myeloperoxidase or
      lipoprotein-associated phospholipase A2 mass and change from baseline in aorta
      and carotid TBRmds. Baseline and change from baseline in high sensitivity C
      reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble
      intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and
      matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from
      baseline in carotid or aorta TBRmds. CONCLUSIONS: Our data show that, in patients
      with coronary heart disease or at high risk of coronary heart disease on stable
      lipid-lowering therapy, circulating myeloperoxidase levels are associated with
      carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the
      Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in
      Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk
      Factors [dal-PLAQUE]; NCT00655473).

PMID- 24135324
TI  - Are the culprit lesions severely stenotic?

PMID- 24135325
TI  - Surgical repair of complex endocarditis.

PMID- 24135326
TI  - Statin therapy resolves coronary artery inflammation.

PMID- 24135327
TI  - LA volume by CMR distinguishes idiopathic from pulmonary hypertension due to
      HFpEF.

PMID- 24135328
TI  - Temporal course of vessel healing and neoatherosclerosis after DES implantation.

PMID- 24135329
TI  - The myth of the mild vulnerable plaques.

PMID- 24135331
TI  - Should the tip-apex distance (TAD) rule be modified for the proximal femoral nail
      antirotation (PFNA)? A retrospective study.
AB  - BACKGROUND: Unstable proximal femoral fractures are common and challenging for
      the orthopaedic surgeon. Often, these are treated with intramedullary nails. The
      most common mode of failure of any device to treat these fractures is cut-out.
      The Synthes proximal femoral nail antirotation (PFNA) is unique because it is the
      only proximal femoral intramedullary nail which employs a helical blade in lieu
      of a lag screw. The optimal tip-apex distance is 25 mm or less for a dynamic hip
      screw. The optimal blade tip placement is not known for the PFNA. AIM: The aim of
      this study is to determine if the traditional tip-apex distance rule (<25 mm)
      applies to the PFNA. METHOD: A retrospective study of all proximal femoral
      fractures treated with the PFNA in Western Australian public teaching hospitals
      between August 2006 and October 2007 was performed. Cases were identified from
      company and theatre implant use records. Patient demographic data was obtained
      from hospital records. Fractures were classified according to Arbeitsgemeinschaft
      fur Osteosynthesefragen/Association for the Study of Internal Fixation. Fracture
      reduction, distal locking type and blade position within the head (tip-apex
      distance and Cleveland zone) were recorded from the intraoperative and immediate
      postoperative radiographs. Postoperative radiographs obtained in the routine
      treatment of patients were studied for review looking primarily for cut-out.
      Clinical outcomes were measured with the Oxford hip score. RESULTS: One hundred
      eighty-eight PFNAs were implanted during the study period, with 178 cases
      included in this study. Ninety-seven patients could be followed up clinically.
      There were 18 surgical implant-related failures (19%). The single most common
      mode of failure was cut-out in six cases (6.2%). Three cut-outs (two medial
      perforation and one varus collapse) occurred with tip-apex distance (TAD) less
      than 20 mm. There was no cut-out in cases where the TAD was from 20-30 mm. There
      were three implant-related failures (nail fracture, missed nail and loose locking
      screw), four implant-related femoral fractures, two non-unions, two delayed
      unions and one loss of reduction. CONCLUSION: The PFNA is a suitable fixation
      device for the treatment of unstable proximal femoral fractures. There were still
      a relatively large number of cut-outs, and the tip-apex distance in the failures
      showed a bimodal distribution, not like previously demonstrated with dynamic hip
      screw. We propose that the helical blade behaves differently to a screw, and
      placement too close to the subchondral bone may lead to penetration through the
      head.

PMID- 24135332
TI  - [Fatal acute polyradiculoneuritis following pneumococcal pneumonia].

PMID- 24135333
TI  - Association of primary cutaneous lichenoid amyloidosis and disseminated
      superficial actinic porokeratosis without superimposition.

PMID- 24135334
TI  - Acute and subchronic effects of buspirone on attention and impulsivity in the
      five-choice serial reaction time task in rats.
AB  - Serotonin (5-HT)-related drugs are extensively employed in the treatment of
      mental disorders. However, the roles of the central serotonergic system in
      impulse control over environmental stimuli remain to be elucidated. The present
      study demonstrated acute and subchronic effects of a 5-HT1A receptor partial
      agonist, buspirone, on the performance of rats in response control indexed by the
      attentional accuracy and impulsive reactivity in the five-choice serial reaction
      time task (5-CSRTT). Acute buspirone (0.5mg/kg) affected accuracy, whereas
      subchronic buspirone treatment augmented impulsivity. Moreover, a subchronic
      buspirone regimen potentiated the acute buspirone-induced reduction in motor
      impulsivity. Our data suggested that a time-dependent mechanism was involved in
      the serotonin-associated behavioral control of response accuracy and motoric
      impulsivity. 

PMID- 24135335
TI  - The relationship between the phenotype of Parkinson's disease and levodopa
      induced dyskinesia.
AB  - Levodopa has been demonstrated to be an effective medication for Parkinson's
      disease (PD), but its long-term use is complicated by the subsequent development
      of dyskinesias. Few studies have distinguished distinct PD subtypes associated
      with the occurrence of Levodopa-Induced Dyskinesia (LID). Therefore, we performed
      a retrospective analysis to determine if the specific phenotype of PD and other
      epidemiological factors are associated with the development of LID. Of 367 PD
      patients taking levodopa, 101 of them developed LID. Multivariate logistic
      regression analysis demonstrated that initial tremor-dominant manifestation was
      associated with a reduced risk of LID, independent of other risk factors, such as
      age at the onset of PD, the duration and dose of levodopa. 

PMID- 24135336
TI  - Cellular localization of the atypical isoforms of protein kinase C
      (aPKCzeta/PKMzeta and aPKClambda/iota) on the neuromuscular synapse.
AB  - Several classic and novel protein kinase C (PKC) isoforms are selectively
      distributed in specific cell types of the adult neuromuscular junction (NMJ), in
      the neuron, glia and muscle components, and are involved in many functions,
      including neurotransmission. Here, we investigate the presence in this
      paradigmatic synapse of atypical PKCs, full-length atypical PKC zeta (aPKCzeta),
      its separated catalytic part (PKMzeta) and atypical lambda-iota PKC
      (aPKClambda/iota). High resolution immunohistochemistry was performed using a pan
      atypical PKC antibody. Our results show moderate immunolabeling on the three
      cells (presynaptic motor nerve terminal, teloglial Schwann cell and postsynaptic
      muscle cell) suggesting the complex involvement of atypical PKCs in synaptic
      function. 

PMID- 24135337
TI  - Pharmacological characteristics of zolpidem-induced catalepsy in the rat.
AB  - Zolpidem is a non-benzodiazepine hypnotic drug acting preferentially at alpha1
      containing GABAA receptors expressed in various parts of the brain, including the
      basal ganglia. The aim of the present study was to provide preliminary
      characteristics of zolpidem-induced catalepsy in Wistar rats. Zolpidem (2.5
      10.0mg/kg), but not diazepam and midazolam, produced dose-dependent cataleptic
      responses in the bar test, which were similar to those produced by a reference
      antipsychotic drug, haloperidol. Zolpidem-induced catalepsy was abolished by a
      benzodiazepine site antagonist, flumazenil (5.0mg/kg), D2/3 receptor agonist,
      quinpirole (1.0mg/kg), and a non-competitive NMDA receptor antagonist, MK-801
      (0.1mg/kg), but not by a non-selective opioid receptor antagonist, naltrexone
      (3.0mg/kg). The present results indicate that systemic injections of zolpidem may
      produce short-lasting, neuroleptic-like catalepsy in the rat. 

PMID- 24135338
TI  - The impact of rectification on the electrically evoked long-latency reflex of the
      biceps brachii muscle.
AB  - Long latency reflexes (LLR) were elicited electrically and obtained by full wave
      rectified and non-rectified data recordings in 10 healthy subjects. After single
      or train stimuli (sensory radial nerve; interstimulus interval 3ms) amplitude and
      peak latency values were measured over the bent biceps brachii (BB) muscle,
      either without or with 1.5kg weight load. After rectification, mean LLR amplitude
      values made up 30% of the non-rectified data, independent from the stimulus type
      and weight load. In the non-rectified data, a significant gain in amplitude
      resulted from train stimuli compared with single stimuli, and from weight load
      compared to no weight load. No such significant difference was detected when
      rectified data were analysed. Furthermore, average amplitude values of rectified
      and non-rectified curves were studied using 11 sine waves and damped sine waves
      with equal phase intervals that were varied from 0 degrees  up to 34.4 degrees .
      Phase shifts ranging from 10 degrees  to 25 degrees  resulted in excess amplitude
      decline of rectified data compared with non-rectified data. The long and
      polysynaptic course that LLR information takes leads to considerable overlap of
      responses to subsequent stimuli. This overlap of motor unit potentials forming
      the LLR obviously results in excess amplitude cancellation after rectification as
      shown for sine and damped sine waves. Rectification leads to an increase in the
      frequency content of the data that renders it prone to phase cancellation. In the
      present study, this cancellation was harmful as it prevented detection of
      important factors of influence such as stimulus strength and motor unit
      recruitment level. 

PMID- 24135340
TI  - Etiology and genes.

PMID- 24135342
TI  - Classification of shapes (auricle/ external auditory canal).

PMID- 24135343
TI  - Imaging diagnosis.

PMID- 24135344
TI  - Audiometry.

PMID- 24135345
TI  - Bone-conduction auditory brainstem response and bone-conduction auditory steady
      state response.

PMID- 24135346
TI  - Development of the auricle and external auditory canal.

PMID- 24135347
TI  - Development of rib cartilage.

PMID- 24135348
TI  - Deciding on the position for auricular reconstruction.

PMID- 24135349
TI  - Anomalies of the auditory ossicles.

PMID- 24135350
TI  - Follow-up of psychological changes in patients prior to surgery.

PMID- 24135351
TI  - Otitis media and subcutaneous abscess while awaiting surgery.

PMID- 24135352
TI  - Deciding on the timing and method of surgery.

PMID- 24135354
TI  - Reconstruction of the auricle with autogenous rib cartilage grafts.

PMID- 24135355
TI  - Joint surgery for elevation of the auricle and construction of the EAC.

PMID- 24135356
TI  - Joint surgery for elevation of the auricle and construction of the EAC. 2.
      construction of the external auditory canal/middle ear.

PMID- 24135357
TI  - Elevation of the auricle without canal/tympanoplasty.

PMID- 24135359
TI  - Postoperative infection of the external auditory canal.

PMID- 24135360
TI  - Skin necrosis.

PMID- 24135361
TI  - Facial nerve palsy.

PMID- 24135362
TI  - Chest wall deformity at the site of costal cartilage harvesting.

PMID- 24135364
TI  - Management of the auricle.

PMID- 24135365
TI  - Postoperative management of the reconstructed external auditory canal.

PMID- 24135366
TI  - Hair removal.

PMID- 24135368
TI  - Effect of lateralization of the reconstructed eardrum on postoperative hearing.

PMID- 24135369
TI  - Temporal bone computed tomography of patients with poor postoperative hearing
      improvement after surgery for atresia of the external auditory canal.

PMID- 24135371
TI  - In cases of bilateral microtia, the number of surgical procedures would double.
      Introduction.

PMID- 24135372
TI  - Prevention of transfusion-transmitted cytomegalovirus infection after allogeneic
      HCT: the debate continues.

PMID- 24135373
TI  - Feasibility and safety of single-incision laparoscopic splenectomy: a systematic
      review.
AB  - OBJECTIVE: The aim of this review was to evaluate the feasibility, safety, and
      potential benefits of single-incision laparoscopic splenectomy (SILS-Sp).
      METHODS: We conducted a systemic review of literature between 2009 and 2012 to
      retrieve all relevant articles. RESULTS: A total of 29 studies with 105 patients
      undergoing SILS-Sp were reviewed. Fifteen studies used a commercially available
      single-port device. The range of body mass index was 14.7-41.4 kg/m(2). Six
      studies described combined operations including cholecystectomy (n = 8), mesh
      pexy (n = 1), and pericardial devascularizaion (n = 1). The ranges of operative
      times and estimated blood losses were 28-420 min and 0-350 mL, respectively. Of
      105 patients, three patients (2.9%) required additional ports, two patients
      (1.9%) were converted to open, and three patients (2.9%) to conventional
      multiport laparoscopic splenectomy (overall conversion rate, 4.8%). Postoperative
      bleeding occurred in two patients (1.9%) who both required reoperation. Overall
      mortality was 0% (0/105). The length of postoperative stay varied across reports
      (1-11 d). Among four comparative studies, one showed greater estimated blood loss
      and lower numeric pain rating scale score in the SILS-Sp group than in the
      multiport laparoscopic splenectomy group (206.25 +/- 142.45 versus 111.11 +/-
      99.58 mL) and (3.81 +/- 0.91 versus 4.56 +/- 1.29), respectively. Another
      comparative study showed that SILS-Sp was associated with a shorter operative
      time (92.5 versus 172 min; P = 0.003), lower conversion rate, equivalent length
      of hospital stay, reduced mortality, similar morbidity, and comparable
      postoperative narcotic requirements. CONCLUSIONS: In early series of highly
      selected patients, SILS-Sp appears to be feasible and safe when performed by
      experienced laparoscopic surgeons. However, as an emerging operation, publication
      bias is a factor that should be considered before we can draw an objective
      conclusion.

PMID- 24135374
TI  - Sternal fracture--an analysis of the National Trauma Data Bank.
AB  - BACKGROUND: The clinical significance of sternal fractures (SFs) after blunt
      trauma is heavily debated. We aimed to test the hypothesis that isolated SF is
      not associated with significant morbidity or mortality. MATERIALS AND METHODS:
      The National Trauma Data Bank (NTDB) sets for 2007-2010 were retrospectively
      examined. Adult subjects with SF were identified by International Classification
      of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Data
      collected included demographics, mechanisms of injury, clinical variables, and in
      hospital mortality. The primary outcome measure was in-hospital mortality.
      Secondary outcome measures included hospital length of stay, intensive care unit
      days, and ventilator days. RESULTS: A total of 32,746 subjects with SF were
      included. Motor vehicle crash (MVC) was the most common mechanism (84%) in this
      group and SF was present in 3.7% of all patients admitted after MVC. The mean age
      was 51 y, 66% were males, and most were white (74%). Overall in-hospital
      mortality was 8.8% and mortality with isolated SF was 3.5%. Increasing thoracic
      fracture burden (rib fracture, clavicular fracture, and scapular fracture) was
      associated with increasing hospital length of stay, intensive care unit days,
      ventilator days, and mortality. On multivariate regression analysis, other
      significant predictors of mortality were cardiac arrest, acute respiratory
      distress syndrome, pulmonary embolism, blunt cardiac injury, pulmonary contusion,
      increasing age, and lack of insurance. CONCLUSIONS: SFs occur in 3.7% of victims
      after MVC. With isolated SF, the mortality rate is low (3.5%); the tendency for
      poorer outcomes is most heavily influenced by associated injuries (pulmonary
      contusions, other thoracic fractures), complications (cardiac arrest, pulmonary
      embolism, acute respiratory distress syndrome), comorbidities (currently on or
      requiring dialysis, residual neurologic deficit from stroke), and lack of
      insurance.

PMID- 24135375
TI  - Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study.
AB  - BACKGROUND: Valproic acid (VPA) has been shown to improve survival in animal
      models of hemorrhagic shock at a dose of 300 mg/kg. Our aim was to identify the
      ideal dose through dose-escalation, split-dosing, and dose de-escalation
      regimens. MATERIALS AND METHODS: Rats were subjected to sublethal 40% hemorrhage
      and treated with vehicle or VPA (dose of 300, 400, or 450 mg/kg) after 30 min of
      shock. Acetylated histones and activated proteins from the PI3K-Akt-GSK-3beta
      survival pathway at different time points were quantified by Western blot
      analysis. In a similar model, a VPA dose of 200 mg/kg followed 2 h later by
      another dose of 100 mg/kg was administered. Finally, animals were subjected to a
      lethal 50% hemorrhage and VPA was administered in a dose de-escalation manner
      (starting at dose of 300 mg/kg) until a significant drop in percent survival was
      observed. RESULTS: Larger doses of VPA resulted in greater acetylation of histone
      3 and increased activation of PI3K pathway proteins. Dose-dependent differences
      were significant in histone acetylation but not in the activation of the survival
      pathway proteins. Split-dose administration of VPA resulted in similar results to
      a single full dose. Survival was as follows: 87.5% with 300 and 250 mg/kg of VPA,
      50% with 200 mg/kg of VPA, and 14% with vehicle-treated animals. CONCLUSIONS:
      Although higher doses of VPA result in greater histone acetylation and activation
      of prosurvival protein signaling, doses as low as 250 mg/kg of VPA confer the
      same survival advantage in lethal hemorrhagic shock. Also, VPA can be given in a
      split-dose fashion without a reduction in its cytoprotective effectiveness.

PMID- 24135376
TI  - Effects of additional laparoscopic cholecystectomy on outcomes of laparoscopic
      gastrectomy in patients with gastric cancer based on a national administrative
      database.
AB  - BACKGROUND: Little information is available on the effects of adding laparoscopic
      cholecystectomy to laparoscopic gastrectomy on outcomes of patients with gastric
      cancer. The aim of this study is to investigate the effects of adding
      laparoscopic cholecystectomy to laparoscopic gastrectomy on outcomes in patients
      with gastric cancer using a national administrative database. METHODS: A total of
      14,006 patients treated with laparoscopic gastrectomy for gastric cancer were
      referred to 744 hospitals in Japan between 2009 and 2011. Patients were divided
      into two groups, those who also underwent simultaneous laparoscopic
      cholecystectomy for gallbladder stones (n = 1484) and those who underwent
      laparoscopic gastrectomy alone (n = 12,522). Laparoscopy-related complications,
      in-hospital mortality, length of stay, and medical costs during hospitalization
      were compared in the patient groups. RESULTS: Multiple logistic regression
      analysis revealed that adding laparoscopic cholecystectomy did not affect
      laparoscopy-related complications (odds ratio, 1.02; 95% confidence interval
      [CI], 0.84-1.24; P = 0.788) or in-hospital mortality (odds ratio, 1.16; 95% CI,
      0.49-2.76; P = 0.727). Multiple linear regression analysis also showed that
      adding laparoscopic cholecystectomy did not affect the length of stay
      (unstandardized coefficient, 0.37 d; 95% CI, -0.47 to 1.22 d; P = 0.389).
      However, adding laparoscopic cholecystectomy was associated with significantly
      increased medical costs during hospitalization (unstandardized coefficient,
      $1256.0 (95% CI, $806.2-$1705.9; P < 0.001). CONCLUSIONS: This study demonstrated
      that adding laparoscopic cholecystectomy did not affect outcomes of patients
      undergoing laparoscopic gastrectomy for gastric cancer, although medical costs
      during hospitalization were significantly increased.

PMID- 24135377
TI  - The role of remote ischemic preconditioning in organ protection after cardiac
      surgery: a meta-analysis.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) appears to protect distant
      organs from ischemia-reperfusion injury. We undertook meta-analysis of clinical
      studies to evaluate the effects of RIPC on organ protection and clinical outcomes
      in patients undergoing cardiac surgery. METHODS: A review of evidence for
      cardiac, renal, and pulmonary protection after RIPC was performed. We also did
      meta-regressions on RIPC variables, such as duration of ischemia, cuff pressure,
      and timing of application of preconditioning. Secondary outcomes included length
      of hospital and intensive care unit stay, duration of mechanical ventilation, and
      mortality at 30 days. RESULTS: Randomized control trials (n = 25) were included
      in the study for quantitative analysis of cardiac (n = 16), renal (n = 6), and
      pulmonary (n = 3) protection. RIPC provided statistically significant cardiac
      protection (standardized mean difference [SMD], -0.77; 95% confidence interval
      [CI], -1.15, -0.39; Z = 3.98; P < 0.0001) and on subgroup analysis, the
      protective effect remained consistent for all types of cardiac surgical
      procedures. However, there was no evidence of renal protection (SMD, 0.74; 95%
      CI, 0.53, 1.02; Z = 1.81; P = 0.07) or pulmonary protection (SMD, -0.03; 95% CI, 
      0.56, 0.50; Z = 0.12; P = 0.91). There was no statistical difference in the short
      term clinical outcomes between the RIPC and control groups. CONCLUSIONS: RIPC
      provides cardiac protection, but there is no evidence of renal or pulmonary
      protection in patients undergoing cardiac surgery using cardiopulmonary bypass.
      Larger multicenter trials are required to define the role of RIPC in surgical
      practice.

PMID- 24135378
TI  - Can we consider day-case laparoscopic cholecystectomy for acute calculous
      cholecystitis? Identification of potentially eligible patients.
AB  - BACKGROUND: Day-case laparoscopic cholecystectomy has not yet been validated for
      acute cholecystitis. We sought to identify a subgroup of acute cholecystitis
      patients having been hospitalized overnight after laparoscopic cholecystectomy
      but who could have been eligible for day-case surgery. METHODS: We identified
      patients treated for acute cholecystitis with laparoscopic cholecystectomy in our
      university medical center between May 1, 2010, and May 31, 2012, and who lacked
      contraindications for day-case surgery. In a second step, we assumed that
      patients hospitalized for <3 d would have been eligible for day-case surgery. We
      then compared patients hospitalized for <=3 d with those hospitalized for >3 d in
      terms of demographic data, laboratory test results, and surgical procedures.
      RESULTS: The study population comprised 86 men and 82 women (median age: 57 y;
      age range: 18-90 y). Contraindications for day-case surgery were identified
      preoperatively in 23% of the cases (39 of 168) and intraoperatively in another
      23% of the cases. The proportion of patients hospitalized for <3 d was 41% (69 of
      168) when considering the intention-to-treat population and 57% (51 of 90) when
      considering patients with no contraindications to day-case surgery. Forty percent
      of the patients hospitalized for >=3 d (16 of 39) suffered from postoperative
      pain that was poorly controlled by oral analgesics. Abdominal drainage was the
      only predictive factor for hospitalization <3 d (odds ratio [95% confidence
      interval] = 0.13 [0.02-0.71]; P = 0.01). CONCLUSIONS: Day-case laparoscopic may
      be feasible in selected patients with mild or moderate acute calculous
      cholecystitis. Our present results may be of use in designing a study of day-case
      surgery for acute calculous cholecystitis and related changes in the management
      of these patients.

PMID- 24135379
TI  - Stearoyl-CoA desaturase plays an important role in proliferation and
      chemoresistance in human hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is often diagnosed at an advanced
      stage, when it is not amenable for aggressive therapies such as surgical
      resection or liver transplantation. Current therapeutic options achieve clinical
      responses in only a small percentage of cases. As a consequence, effective
      approaches for prevention and treatment are greatly needed. Altered lipid
      metabolism has been recently linked to HCC pathogenesis. The aims of this study
      were to define the cellular and molecular mechanisms linking stearoyl-CoA
      desaturase (SCD), the rate-limiting enzyme and an essential regulator of lipid
      homeostasis in liver cells, to carcinogenesis in HCC. MATERIAL AND METHODS: HCC
      and normal liver specimens were collected. Human HCC cell lines: HepG2, Hep3B,
      and PLC/PLF/5 were used for immunoblot, cell viability, proliferation, and
      apoptosis assays. Small interfering RNAs were used for genetic inhibition, and
      10, 12 conjugated linoleic acid was used for pharmacologic SCD inhibition.
      RESULTS: SCD was strongly expressed in surgically resected HCC (n = 64) and
      various human HCC cell lines (HepG2, Hep3B, and PLC/PLF/5). The levels of SCD
      negatively correlated with degree of tumor differentiation (P < 0.01). Treatment
      of these HCC cell lines with a panel of chemotherapeutic drugs resulted in a time
      dependent, phosphatidylinositol 3 kinase- and c-Jun N-terminal kinases1/2
      mediated upregulation of SCD expression, which paralleled the degree of
      resistance to drug-induced apoptosis. Specific genetic or pharmacologic SCD
      suppression resulted in inhibition of cell proliferation (P < 0.001) and
      significantly increased sensitivity to chemotherapy-induced apoptosis.
      CONCLUSIONS: Our data suggest that increased SCD expression plays an important
      role in HCC development and resistance to chemotherapy-induced apoptosis, and
      this is in part mediated by phosphatidylinositol 3 kinase/c-Jun N-terminal
      kinases activation. Specific targeted interruption of this pathway in HCC could
      be a desirable approach in designing novel therapeutic strategies.

PMID- 24135380
TI  - Species or local environment, what determines the infection of rodents by
      Toxoplasma gondii?
AB  - Toxoplasmosis is largely present in rural areas but its spatial distribution in
      this environment remains poorly known. In particular, it is unclear if areas of
      high density of cats, the only hosts excreting Toxoplasma gondii, constitute foci
      of high prevalence. To improve our understanding of the spatial distribution of
      T. gondii in rural areas, we performed a serological survey in rodents from two
      villages in France. We trapped 710 rodents including commensal rats and meadow or
      forest voles and mice. The presence of T. gondii was examined using PCR, mice
      inoculation and modified agglutination test for antibodies (MAT). We conducted
      multivariate and discriminant analyses to identify biological, ecological or
      spatial variables that could explain T. gondii serology in rodents. We then used
      a logistic regression to assess the relative influence of each explanatory
      variable. Overall seroprevalence was 4.1%. Commensal-rats were more infected
      (12.5%) than non-commensal species (3.7%). However, the major determinant of the
      risk of infection was the distance to the nearest farm (OR = 0.75 for 100 m),
      which explained the risk in all species or non-commensal species only. We
      contrast the role of species characteristics and that of the local environment,
      and discuss the risk of environmental contamination for humans.

PMID- 24135381
TI  - Linear IgA bullous disease presenting as toxic epidermal necrolysis: a case
      report and review of the literature.
AB  - A 91-year-old female presented with widespread skin sloughing and bullae
      clinically mimicking toxic epidermal necrolysis (TEN). The patient was on
      multiple antibiotics, including vancomycin and piperacillin/tazobactam.
      Histopathology and direct immunofluorescence were consistent with a diagnosis of
      linear IgA bullous disease (LABD). In a PubMed review of the literature from 1975
      to the present, there have been 15 cases of LABD presenting as TEN clinically and
      with characteristic linear IgA deposits on direct immunofluorescence studies.
      Vancomycin and phenytoin were the most commonly implicated medications. Twelve
      patients saw a resolution or healing of skin lesions after discontinuation of the
      implicated medication. There were, however, 5 patients who died of complications
      related to their comorbidities. It is important to include LABD in the
      differential diagnosis when evaluating patients who clinically present with TEN.

PMID- 24135382
TI  - Overall care cost comparison between robotic and laparoscopic surgery for
      endometrial and cervical cancer.
AB  - OBJECTIVE: The aim of our medico-economic study was to compare robotic surgery
      cost with conventional laparoscopic cost in endometrial and cervical cancer.
      STUDY DESIGN: Our study included laparoscopic and robot-assisted procedures
      (radical hysterectomies and lymphadenectomies) for endometrial or cervical cancer
      ever since first using the Da Vinci(r) in 2008 within a hospital setting. In the
      hospital perspective, direct costs were determined by examining the overall
      medical pathway for each type of intervention. Actual costs were calculated for
      27 conventional laparoscopic procedures and for 30 robot-assisted procedures
      including initial cost of the robot and its maintenance. We estimated the
      complete medical "overall care" costs by adding the costs of consultations,
      surgery and post-operative hospital stay to the costs of any eventual emergency
      consultation and/or hospitalisation within the two months that followed surgery.
      A sensitivity analysis was performed to evaluate the effects of variable
      modulations. RESULTS: For endometrial cancer, surgical procedure cost for robotic
      assisted surgery was ?7402 compared to ?2733 for conventional laparoscopic
      surgery. When considering overall medical care, the patient treatment average
      cost was ?6666 for the laparoscopic group (with an average length of stay of 5.27
      days) as compared to ?10,816 for robotic group (with an average hospital stay of
      4.60 days), p=0.39. For cervical cancer, average surgical cost with robotic
      assisted surgery was ?8501 compared to conventional laparoscopic surgery at
      ?3239. For cervical cancer, overall care average cost was ?7803 for the
      laparoscopic group (with an average length of stay of 5.83 days) as compared to
      ?12,211 for the robotic group (with an average hospital stay of 4.70 days)
      p=0.07. Sensitivity analysis results confirmed the cost overrun with the use of
      robotic assisted surgery. CONCLUSIONS: Conventional laparoscopy was less
      expensive in our institution than robotic-assisted surgery for the surgery of
      endometrial (1:2.7) and cervical (1:2.6) cancers. When considering overall
      medical care, the use of robotic-assisted surgery was found to be 1.6 times more
      expensive than conventional surgery.

PMID- 24135383
TI  - A pilot study on the combined use of letrozole, mifepristone and misoprostol in
      termination of first trimester pregnancy up to 9 weeks' gestation.
AB  - OBJECTIVE: To assess the feasibility of adding letrozole to the standard regimen
      of mifepristone and misoprostol for termination of pregnancy up to 63 days. STUDY
      DESIGN: We recruited 50 subjects who had requested legal termination of pregnancy
      up to 63 days. Medical abortion was performed with a singe dose of 200 mg
      mifepristone and 10 mg of letrozole daily for 3 days followed by 800 mcg vaginal
      misoprostol. RESULTS: The complete abortion rate was 98% (95% CI: 94-100%). The
      median induction-to-abortion interval of the regimen was 5.1 h (range 1.2-56 h).
      No serious adverse effects were reported. CONCLUSIONS: The results of this pilot
      study suggest that a regimen of mifepristone, letrozole and misoprostol is
      associated with a high complete abortion rate without major adverse events.

PMID- 24135384
TI  - Validating a natural language processing tool to exclude psychogenic nonepileptic
      seizures in electronic medical record-based epilepsy research.
AB  - RATIONALE: As electronic health record (EHR) systems become more available, they
      will serve as an important resource for collecting epidemiologic data in epilepsy
      research. However, since clinicians do not have a systematic method for coding
      psychogenic nonepileptic seizures (PNES), patients with PNES are often
      misclassified as having epilepsy, leading to sampling error. This study validates
      a natural language processing (NLP) tool that uses linguistic information to help
      identify patients with PNES. METHODS: Using the VA national clinical database,
      2200 notes of Iraq and Afghanistan veterans who completed video
      electroencephalograph (VEEG) monitoring were reviewed manually, and the veterans
      were identified as having documented PNES or not. Reviewers identified PNES
      related vocabulary to inform a NLP tool called Yale cTakes Extension (YTEX).
      Using NLP techniques, YTEX annotates syntactic constructs, named entities, and
      their negation context in the EHR. These annotations are passed to a classifier
      to detect patients without PNES. The classifier was evaluated by calculating
      positive predictive values (PPVs), sensitivity, and F-score. RESULTS: Of the 742
      Iraq and Afghanistan veterans who received a diagnosis of epilepsy or seizure
      disorder by VEEG, 44 had documented events on VEEG: 22 veterans (3.0%) had
      definite PNES only, 20 (2.7%) had probable PNES, and 2 (0.3%) had both PNES and
      epilepsy documented. The remaining 698 veterans did not have events captured
      during the VEEG admission and/or did not have a definitive diagnosis. Our
      classifier achieved a PPV of 93%, a sensitivity of 99%, and a F-score of 96%.
      CONCLUSION: Our study demonstrates that the YTEX NLP tool and classifier is
      highly accurate in excluding PNES, diagnosed with VEEG, in EHR systems. The tool
      may be very valuable in preventing false positive identification of patients with
      epilepsy in EHR-based epidemiologic research.

PMID- 24135385
TI  - Low prevalence of subclinical atherosclerosis in asymptomatic patients with type
      1 diabetes in a European Mediterranean population.
AB  - OBJECTIVE: To evaluate the presence of early carotid and coronary atherosclerosis
      in asymptomatic patients with type 1 diabetes with no history of ischemic heart
      disease. RESEARCH DESIGN AND METHODS: One hundred and fifty patients with type 1
      diabetes (58% males; 38.6 +/- 8.1 years, 20.4 +/- 8.1 years of evolution; HbA1c
      8.1 +/- 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50
      nondiabetic control subjects age and sex matched were studied. Carotid
      ultrasonography to determine common carotid artery intima-media thickness (c-IMT)
      and the presence of atheroma plaques and cardiac computed tomography for calcium
      analysis and quantification (coronary artery calcium score [CACS]) were
      performed. RESULTS: Most patients with type 1 diabetes and control subjects
      displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS >=1
      were older and had higher HbA1c (44.5 +/- 5.1 vs. 36.7 +/- 8.1 years [P < 0.001]
      and 8.5 +/- 1.1 vs. 7.8 +/- 1.0% [P < 0.003], respectively) and longer evolution
      of diabetes (25.4 +/- 9.2 vs. 19.3 +/- 7.4 years, P < 0.005) and mean c-IMT (0.67
      +/- 0.18 vs. 0.53 +/- 0.11 mm, P < 0.001) compared with patients with CACS of 0.
      Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex
      (P < 0.03) were significantly and positively associated with CACS >=1. Mean c-IMT
      was significantly higher in patients with type 1 diabetes (0.55 +/- 0.14 vs. 0.48
      +/- 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control
      subjects). Multivariant logistic regression analysis showed that c-IMT was
      related to CACS (beta = 6.87, P < 0.001). CONCLUSIONS: A small percentage of
      patients with type 1 diabetes showed data suggestive of subclinical
      atherosclerosis. Universal screening of coronary disease in this population is
      not justified. Carotid ultrasonography may be useful for screening in the subset
      of patients with cardiovascular risk factors and long disease evolution.

PMID- 24135386
TI  - Cost-effectiveness of alternative thresholds of the fasting plasma glucose test
      to identify the target population for type 2 diabetes prevention in adults aged
      >=45 years.
AB  - OBJECTIVE: The study objective was to evaluate the cost-effectiveness of
      alternative fasting plasma glucose (FPG) thresholds to identify adults at high
      risk for type 2 diabetes for diabetes preventive intervention. RESEARCH DESIGN
      AND METHODS: We used a validated simulation model to examine the change in
      lifetime quality-adjusted life years (QALYs) and medical costs when the FPG
      threshold was progressively lowered in 5-mg/dL decrements from 120 to 90 mg/dL.
      The study sample includes nondiabetic adults aged >=45 years in the United States
      using 2006-2010 data from the National Health and Nutrition Examination Survey.
      High-risk individuals were assumed to receive a lifestyle intervention, as that
      used in the Diabetes Prevention Program. We calculated cost per QALY by dividing
      the incremental cost by incremental QALY when lowering the threshold to the next
      consecutive level. Medical costs were assessed from a health care system
      perspective. We conducted univariate and probabilistic sensitivity analyses to
      assess the robustness of the results using different simulation scenarios and
      parameters. RESULTS: Progressively lowering the FPG threshold would monotonically
      increase QALYs, cost, and cost per QALY. Reducing (in 5-mg/dL decrements) the
      threshold from 120 to 90 mg/dL cost $30,100, $32,900, $42,300, $60,700, $81,800,
      and $115,800 per QALY gained, respectively. The costs per QALY gained were lower
      for all thresholds under a lower-cost and less-effective intervention scenario.
      CONCLUSIONS: Lowering the FPG threshold leads to a greater health benefit of
      diabetes prevention but reduces the cost-effectiveness. Using the conventional
      benchmark of $50,000 per QALY, a threshold of 105 mg/dL or higher would be cost
      effective. A lower threshold could be selected if the intervention cost could be
      lowered.

PMID- 24135387
TI  - Elevated HbA1c and fasting plasma glucose in predicting diabetes incidence among
      older adults: are two better than one?
AB  - OBJECTIVE: To determine which measures-impaired fasting glucose (IFG), elevated
      HbA1c, or both-best predict incident diabetes in older adults. RESEARCH DESIGN
      AND METHODS: From the Health, Aging, and Body Composition study, we selected
      individuals without diabetes, and we defined IFG (100-125 mg/dL) and elevated
      HbA1c (5.7-6.4%) per American Diabetes Association guidelines. Incident diabetes
      was based on self-report, use of antihyperglycemic medicines, or HbA1c >=6.5%
      during 7 years of follow-up. Logistic regression analyses were adjusted for age,
      sex, race, site, BMI, smoking, blood pressure, and physical activity.
      Discrimination and calibration were assessed for models with IFG and with both
      IFG and elevated HbA1c. RESULTS: Among 1,690 adults (mean age 76.5, 46% men, 32%
      black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of
      diabetes were 6.2 (95% CI 4.4-8.8) in those with IFG (versus those with fasting
      plasma glucose [FPG] <100 mg/dL) and 11.3 (7.8-16.4) in those with elevated HbA1c
      (versus those with HbA1c <5.7%). When FPG and HbA1c were considered together,
      odds ratios were 3.5 (1.9-6.3) in those with IFG only, 8.0 (4.8-13.2) in those
      with elevated HbA1c only, and 26.2 (16.3-42.1) in those with both IFG and
      elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated
      HbA1c to the model with IFG resulted in improved discrimination and calibration.
      CONCLUSIONS: Older adults with both IFG and elevated HbA1c have a substantially
      increased odds of developing diabetes over 7 years. Combined screening with FPG
      and HbA1c may identify older adults at very high risk for diabetes.

PMID- 24135389
TI  - Metformin, but not rosiglitazone, attenuates the increasing plasma levels of a
      new cardiovascular marker, fibulin-1, in patients with type 2 diabetes.
AB  - OBJECTIVE The extracellular matrix protein fibulin-1 is upregulated in the
      arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations
      in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular
      disease effects in diabetes. We hypothesized that metformin would influence the
      increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODS
      After a 4-week run-in period, 371 eligible patients with T2D were randomized to
      treatment groups in a factorial design including insulin alone (control),
      +metformin, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin
      1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTS
      Plasma fibulin-1 increased in all groups throughout the 2-year period; however,
      the increase was strongly attenuated among patients treated with metformin. A
      highly significant difference was observed when the mean change in plasma fibulin
      1 was compared between metformin- and non-metformin-treated individuals both at
      18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and
      rosiglitazone alone reduced the HbA1c levels to comparable levels and in
      combination even further. CONCLUSIONS Metformin attenuates the increase in plasma
      fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in
      fibulin-1 may reflect an important element in diabetic arteriopathy that can be
      influenced by metformin. 

PMID- 24135390
TI  - Improving fruit and vegetable consumption among low-income customers at farmers
      markets: Philly Food Bucks, Philadelphia, Pennsylvania, 2011.
AB  - INTRODUCTION: We evaluated whether Philly Food Bucks, a bonus incentive program
      at farmers markets, is associated with increased fruit and vegetable consumption
      and Supplemental Nutrition Assistance Program (SNAP) sales at farmers markets in
      low-income areas. METHODS: A convenience sample of 662 customers at 22 farmers
      markets in low-income neighborhoods in Philadelphia, Pennsylvania, was surveyed
      via face-to-face interviews. Questions addressed shopping characteristics, self
      reported change in fruit and vegetable consumption, whether customers tried new
      fruits or vegetables, use of Philly Food Bucks, and demographic information.
      Market-level SNAP sales and Philly Food Bucks redemption data were also collected
      to monitor sales patterns. RESULTS: Philly Food Bucks users were significantly
      more likely than nonusers to report increasing fruit and vegetable consumption
      (OR, 2.4; 95% CI, 1.6-3.7; P < .001) and to report trying new fruits or
      vegetables (OR 1.8; 95% CI, 1.2-2.7; P = .006). At the market level, average SNAP
      sales more than doubled at farmers markets in low-income areas in the first 2
      years of the Philly Food Bucks program. At the city's largest farmers market in a
      low-income area, the program was associated with an almost 5-fold higher increase
      in annual SNAP sales compared with baseline. CONCLUSION: Results from this study
      demonstrate that a bonus incentive program tied to SNAP was associated with self
      reported increases in fruit and vegetable consumption and increased SNAP sales at
      participating farmers markets in low-income communities. More research is
      warranted to evaluate the long-term impact of bonus incentives on farmers market
      use, dietary behaviors, and health outcomes.

PMID- 24135388
TI  - beta-Cell function improvements in grade I/II obese subjects with type 2 diabetes
      1 month after biliopancreatic diversion: results from modeling analyses of oral
      glucose tolerance tests and hyperglycemic clamp studies.
AB  - OBJECTIVE: To investigate the effect of biliopancreatic diversion (BPD) surgery
      on beta-cell function in grade I and II obese patients with type 2 diabetes using
      oral and intravenous glucose loads. RESEARCH DESIGN AND METHODS: Sixty-eight
      women were divided into the following three groups: 19 lean-control (23.0 +/- 2.2
      kg/m(2)) and 18 obese-control (35.0 +/- 4.8 kg/m(2)) subjects with normal glucose
      tolerance, and 31 obese patients with type 2 diabetes (36.3 +/- 3.7 kg/m(2)). Of
      the 31 diabetic women, 64% underwent BPD (n = 20, BMI: 36.5 +/- 3.7 kg/m(2)) and
      were reassessed 1 month after surgery. Oral glucose tolerance tests and
      hyperglycemic clamps were performed. Mathematical modeling was used to analyze
      basal and stimulated beta-cell function, insulin sensitivity (IS), hepatic
      extraction (HE) of insulin, and delay time of beta-cell response to a specific
      plasma glucose concentration. RESULTS: After BPD, restoration of the basal
      disposition index (P < 0.001) and improvement of the stimulated disposition
      indices in oral and intravenous glucose stimulation of the beta-cell were
      observed (P < 0.05). In both dynamic tests, there were no changes in the delay
      time of beta-cell response. IS for oral glucose stimulation (IS(oral)) and
      intravenous clamp glucose stimulation (IS(clamp)) was completely normalized (P <
      0.001). IS(oral) and IS(clamp) increased approximately 5.0-fold and 3.5-fold,
      respectively (P < 0.01). The HE of insulin increased in the basal (P < 0.05) and
      stimulated states (P < 0.01). CONCLUSIONS: beta-Cell function, IS, and HE of
      insulin improved after BPD, which improved glycemic control.

PMID- 24135391
TI  - Partnering with community institutions to increase access to healthful foods
      across municipalities.
AB  - BACKGROUND: Low-income and minority communities have higher rates of nutrition
      related chronic diseases than do high-income and nonminority communities and
      often have reduced availability to healthful foods. Corner store initiatives have
      been proposed as a strategy to improve access to healthful foods in these
      communities, yet few studies evaluating these initiatives have been published.
      COMMUNITY CONTEXT: Suburban Cook County, Illinois, encompasses 125 municipalities
      with a population of more than 2 million. From 2000 through 2009, the percentage
      of low-income suburban Cook County residents increased 41%; African-American
      populations increased 20%, and Hispanic populations increased 44%. A 2012 report
      found that access to stores selling healthful foods was low in several areas of
      the county. METHODS: Beginning in March 2011, the Cook County Department of
      Public Health recruited community institutions (ie, local governments, nonprofit
      organizations, faith-based institutions) who recruited corner stores to
      participate in the initiative. Corner stores were asked to add new, healthful
      foods (May-June 2011) to become eligible to receive new equipment, marketing
      materials, and enhanced community outreach (July 2011-February 2012). OUTCOMES:
      Nine community institutions participated. Of the 53 corner stores approached, 25
      (47%) participated in the trial phase, which included offering 6 healthful foods
      in their stores. Of those, 21 (84%) completed the conversion phase, which
      included expansion of healthful foods through additional equipment and marketing
      and promotional activities. INTERPRETATION: Community institutions can play a key
      role in identifying and engaging corner stores across jurisdictions that are
      willing and able to implement a retail environment initiative to improve access
      to healthful foods in their communities.

PMID- 24135392
TI  - Increasing access to farmers markets for beneficiaries of nutrition assistance:
      evaluation of the farmers market access project.
AB  - INTRODUCTION: Increased acceptance of nutrition benefits at farmers markets could
      improve access to nutritious foods for low-income shoppers. The objective of this
      study was to evaluate a pilot project to increase participation by farmers
      markets and their vendors in the Supplemental Nutrition Assistance Program (SNAP)
      and Special Supplemental Nutrition Program for Women, Infants, and Children
      (WIC). METHODS: The intervention targeted 9 markets in lower-income regions of
      King County, Washington. Markets and vendors were offered subsidized electronic
      benefits transfer (EBT) terminals for processing SNAP, and vendors could apply to
      accept WIC cash value vouchers. WIC staff received information on using SNAP and
      vouchers at farmers markets. We used mixed methods post-implementation to measure
      participation, describe factors in acceptance of benefits, and assess information
      needs for WIC staff to conduct effective outreach. RESULTS: Of approximately 88
      WIC-eligible vendors, 38 agreed to accept vouchers. Ten of 125 vendors installed
      an EBT terminal, and 6 markets installed a central market terminal. The number of
      market stalls accepting SNAP increased from 80 to 143, an increase of 79%.
      Participating vendors wanted to provide access to SNAP and WIC shoppers, although
      redemption rates were low. Some WIC staff members were unfamiliar with markets,
      which hindered outreach. CONCLUSION: Vendors and markets value low-income
      shoppers and, when offered support, will take on some inconvenience to serve
      them. To improve participation and sustainability, we recommend ongoing subsidies
      and streamlined procedures better suited to meet markets' capabilities. Low EBT
      redemption rates at farmers markets suggest a need for more outreach to low
      income shoppers and relationship building with WIC staff.

PMID- 24135393
TI  - Use of interrupted time-series method to evaluate the impact of cigarette excise
      tax increases in Pennsylvania, 2000-2009.
AB  - INTRODUCTION: Scientific evidence shows that cigarette price increases can
      significantly reduce smoking prevalence and smoking initiation among adolescents
      and young adults. However, data are lacking regarding the effectiveness of
      increasing Pennsylvania's cigarette tax to reduce smoking and/or adverse health
      effects of smoking. The objective of our study was to assess the impact of
      cigarette tax increases and resulting price increases on smoking prevalence,
      acute myocardial infarction (AMI) and asthma hospitalization rates, and sudden
      cardiac death (SCD) rates in Pennsylvania. METHODS: We used segmented regression
      analyses of interrupted time series to evaluate the level and trend changes in
      Pennsylvania adults' current smoking prevalence, age-adjusted AMI and asthma
      hospitalization rates, age-specific asthma hospitalization rates, and age
      adjusted SCD rates following 2 cigarette excise tax increases. RESULTS: After the
      first excise tax increase, no beneficial effects were noted on the outcomes of
      interest. The second tax increase was associated with significant declines in
      smoking prevalence for people aged 18 to 39, age-adjusted AMI hospitalization
      rates for men, age-adjusted asthma hospitalizations rates, and SCD rates among
      men. Overall smoking prevalence declined by 5.2% (P = .01), with a quarterly
      decrease of 1.4% (P = .01) for people aged 18 to 39 years. The age-adjusted AMI
      hospitalization rate for men showed a decline of 3.87/100,000 population (P =
      .04). The rate of age-adjusted asthma hospitalizations decreased by 10.05/100,000
      population (P < .001), and the quarterly trend decreased by 3.21/100,000
      population (P < .001). Quarterly SCD rates for men decreased by 1.34/100,000
      population (P < .001). CONCLUSION: An increase in the price of cigarettes to more
      than $4 per 20-cigarette pack was associated with a significant decrease in
      smoking among younger people (aged 18-39). Decreases were also seen in asthma
      hospitalizations and men's age-adjusted AMI hospitalization and SCD rates.
      Further research and policy development regarding the effect of cigarette taxes
      on tobacco consumption should be cognizant of the psychological tipping points at
      which overall price affects smoking patterns.

PMID- 24135394
TI  - Barriers to colorectal cancer screening among American Indian men aged 50 or
      older, Kansas and Missouri, 2006-2008.
AB  - American Indian (AI) men have some of the highest rates of colorectal cancer
      (CRC) in the United States but among the lowest screening rates. Our goal was to
      better understand awareness and discourse about colorectal cancer in a
      heterogeneous group of AI men in the Midwestern United States. Focus groups were
      conducted with AI men (N = 29); data were analyzed using a community
      participatory approach to qualitative text analysis. Several themes were
      identified regarding knowledge, knowledge sources, and barriers to and
      facilitators of screening. Men in the study felt that awareness about colorectal
      cancer was low, and people were interested in learning more. Education strategies
      need to be culturally relevant and specific. 

PMID- 24135396
TI  - Sarcoidosis mimicking metastatic bone disease in head and neck cancer.

PMID- 24135395
TI  - Niemann-Pick disease type C symptomatology: an expert-based clinical description.
AB  - Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease
      leading to disabling neurological manifestations and premature death. The
      estimated disease incidence is 1:120,000 live births, but this likely represents
      an underestimate, as the disease may be under-diagnosed due to its highly
      heterogeneous presentation. NP-C is characterised by visceral, neurological and
      psychiatric manifestations that are not specific to the disease and that can be
      found in other conditions. The aim of this review is to provide non-specialists
      with an expert-based, detailed description of NP-C signs and symptoms, including
      how they present in patients and how they can be assessed. Early disease
      detection should rely on seeking a combination of signs and symptoms, rather than
      isolated findings. Examples of combinations which are strongly suggestive of NP-C
      include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly
      and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms
      and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and
      cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the
      disease when it occurs in combination with other manifestations (e.g.
      splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first
      manifest as slowing and shortening of upward saccades, long before gaze palsy
      onset. While visceral manifestations tend to predominate during the perinatal and
      infantile period (2 months-6 years of age), neurological and psychiatric
      involvement is more prominent during the juvenile/adult period (>6 years of age).
      Psychosis in NP-C is atypical and variably responsive to treatment. Progressive
      cognitive decline, which always occurs in patients with NP-C, manifests as memory
      and executive impairment in juvenile/adult patients. Disease prognosis mainly
      correlates with the age at onset of the neurological signs, with early-onset
      forms progressing faster. Therefore, a detailed and descriptive picture of NP-C
      signs and symptoms may help improve disease detection and early diagnosis, so
      that therapy with miglustat (Zavesca((r))), the only available treatment approved
      to date, can be started as soon as neurological symptoms appear, in order to slow
      disease progression.

PMID- 24135397
TI  - Introduction: recent advances in the understanding and management of multiple
      myeloma.

PMID- 24135398
TI  - Decoding the pathophysiology and the genetics of multiple myeloma to identify new
      therapeutic targets.
AB  - In recent years, significant progress has been achieved in the characterization
      of the transcriptional profiles, gene mutations and structural chromosomal
      lesions in myeloma cells. These studies have identified many candidate
      therapeutic targets, which are recurrently deregulated in myeloma cells. However,
      these targets do not appear, at least individually, to represent universal
      driver(s) of this disease. Furthermore, evaluation of these recurrent lesions
      does not suggest that they converge to a single molecular pathway. Detailed
      integration of molecular and functional data for these candidate targets and
      pathways will hopefully dissect which of them play more critical roles for each
      of the different individual molecular defined subtypes of this disease. This
      review focuses on how recent updates in our understanding of myeloma pathogenesis
      and molecular characterization may impact ongoing and future efforts to develop
      new therapeutics for this disease. 

PMID- 24135399
TI  - Clinical translation in multiple myeloma: from bench to bedside.
AB  - The outlook for patients with multiple myeloma (MM) has improved significantly
      with the development of new and more effective therapies, particularly the
      immunomodulatory agents and proteasome inhibitors. Preclinical and correlative
      science investigations have played a critical role in these advances, providing
      important insights regarding mechanisms of neoplasia, inhibition of tumor growth,
      and drug resistance. This review highlights the evolution of drug development in
      MM, the manner in which preclinical models have contributed to the process of
      drug discovery, and important insights gained during the current era of MM drug
      development. 

PMID- 24135400
TI  - Myeloma: classification and risk assessment.
AB  - Multiple myeloma (MM) is a heterogeneous disease for which several new treatments
      are available. Much has been learned about its biology over the past 15 years. We
      now understand that there are various subtypes of the disease, each one
      associated with different outcomes and clinical pathological features. While a
      detailed classification of the disease into at least seven or eight major
      subtypes is possible, a practical clinical approach classifies the disease into
      high-risk and not-high-risk MM. This classification has allowed for tailored
      approaches to therapy and treatment planning. Furthermore, the discussion of
      outcomes with patients should include risk stratification, as the prospects for
      survival are quite different depending on whether the patient has high-risk MM or
      not. The tools for measuring risk subcategory are widely available and now
      routinely employed in the clinic. The continued search for genetic abnormalities
      that underlie the biology of MM may allow for even better precision therapy in
      the future. 

PMID- 24135401
TI  - Individualized therapy in multiple myeloma: are we there?
AB  - Multiple myeloma (MM), a heterogeneous plasma cell dyscrasia with a variety of
      clinical presentations and outcomes, is undergoing a treatment renaissance. While
      new drug classes have been discovered, a subset of high-risk MM remains
      relatively refractory to treatment. Current risk stratifications models, such as
      Durie-Salmon and the International Staging System, estimate disease burden and
      prognosis. Cytogenetics and gene expression profiles can help further identify
      more aggressive disease. Additionally, molecular and immunophenotypic assessment
      of minimal residual disease (MRD) and different imaging studies can identify
      patients at higher risk for relapse. It is now an opportune time to develop
      algorithms to combine all of the currently available clinical and genomic
      information to begin to inform specific therapeutic intervention in individual
      patients or at least smaller subgroups with similarly behaving disease. 

PMID- 24135402
TI  - Initial treatment of nontransplant patients with multiple myeloma.
AB  - During the last two decades, many steps forward have been made in the treatment
      of multiple myeloma (MM) thanks to the introduction of the novel agents
      thalidomide, lenalidomide, and bortezomib. Despite this, MM remains an incurable
      disease. Elderly patients (>=65 years) represent the majority of subjects.
      Differently from younger (<65 years) and fit patients, elderly patients are
      usually not eligible for transplantation. Gentler approaches with novel agents
      plus conventional chemotherapy with melphalan-prednisone are commonly adopted in
      this setting. Data show that a sequential approach including induction followed
      by consolidation/maintenance therapy is an optimal strategy to improve patient
      outcome. In addition, second-generation novel agents are currently under
      investigation and may represent valuable alternative treatment options in the
      future. 

PMID- 24135403
TI  - Initial treatment of transplant candidates with multiple myeloma.
AB  - Over the last decade, thalidomide, bortezomib, and lenalidomide have been
      introduced into the armamentarium of myeloma therapies. These novel agents have
      improved the rate of complete remission both before and after autologous stem
      cell transplantation (ASCT) without substantially increasing toxicity, which has
      important implications as the achievement of high-quality responses is a
      significant prognostic factor for outcome. This review will focus on the most
      recent results of novel agent-based induction therapies, as well as on
      interesting developments in the transplant phase that are aimed at improving the
      results of conditioning regimens. 

PMID- 24135404
TI  - Evolving strategies in the initial treatment of multiple myeloma.
AB  - Until the advents of novel agents, partial response (PR) or better was the
      established gold standard to initial therapy of multiple myeloma (MM), and
      treatment goals were focused on relieving symptoms, prevention of organ damage,
      and modest improvements in survival. With the introduction of autologous stem
      cell transplant (ASCT), deeper responses, including complete responses (CRs) were
      more frequent, and contributed to longer survival. In the era of novel therapies,
      ASCT remains commonly used and its impact on outcome appears superior, albeit
      less so than when compared with conventional therapy, and its survival benefit is
      yet to be established in either setting. In addition, in non-transplant
      candidates, novel therapies have now significantly improved the overall response
      rates, depth of response, and clinical benefit, to the levels previously only
      observed with ASCT, which now increasingly challenges the role and timing of ASCT
      in eligible patients. Nevertheless, the two approaches of treatment, transplant
      or no transplant, remain commonly accepted. With an improvement in the
      tolerability of newer regimens and the deferral of ASCT in transplant candidates,
      the debate has emerged whether the two-pathway approach to the treatment of newly
      diagnosed myeloma should be re-evaluated. At the same time, treatment goals are
      also shifting. Many believe that MM can be converted into a chronic disease and
      that a functional cure maybe a realistic goal, for at least a proportion of
      patients. This contribution will review these points of discussion and the
      evolving approach to treatment of newly diagnosed MM. 

PMID- 24135405
TI  - New developments in post-transplant maintenance treatment of multiple myeloma.
AB  - Treatment of multiple myeloma (MM) has evolved significantly over the past two
      decades with high-dose chemotherapy and autologous stem cell transplant (ASCT),
      incorporating novel therapies such as proteasome inhibitors (PIs) and
      immunomodulatory drugs (IMiDs) during induction and post-transplant maintenance
      therapies. We reviewed the evolution of maintenance therapy from traditional
      chemotherapy, interferon (IFN), and prednisone to the current use of thalidomide,
      lenalidomide, and bortezomib in the post-transplant maintenance setting. Based on
      existing literature, either thalidomide or lenalidomide can be recommended for
      maintenance therapy post-transplant resulting in improved progression- free
      survival (PFS) and overall survival (OS). Thalidomide is less tolerated than
      lenalidomide and does not improve survival in patient subgroups who had achieved
      at least a very good partial response (VGPR) or who had chromosome 13 deletion.
      Thalidomide maintenance may be even detrimental in patients with high-risk
      cytogenetics. Alternatively, lenalidomide maintenance improves PFS in all
      subgroups of patients including those achieving at least a VGPR and those with
      high-risk cytogenetics, and improves OS in one other study. Bortezomib
      maintenance improves PFS and OS as part of induction and maintenance when
      compared to thalidomide maintenance and it is uncertain as to whether this
      improvement was due to bortezomib used during induction. The future research in
      maintenance therapy may include incorporation of current novel agents and testing
      new oral agents such as pomalidomide, or ixazomib or antibody therapy with
      elotuzumab. 

PMID- 24135406
TI  - Role of consolidation therapy in transplant eligible multiple myeloma patients.
AB  - The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in
      the treatment of multiple myeloma (MM) has continued to evolve in recent years.
      The novel agents thalidomide, bortezomib, and lenalidomide have been successfully
      incorporated into induction therapy in preparation for ASCT and are currently
      being investigated also as post-ASCT consolidation and maintenance therapy.
      Consolidation treatment is generally short term and aims to increase the
      frequency and depth of response obtained with the previous treatment phases,
      including novel agent-based induction therapy and ASCT. This review will focus on
      recent trials of novel agents as post-ASCT consolidation therapy, offering an
      overview of pros and cons of this new treatment strategy in the ASCT sequence for
      MM patients. 

PMID- 24135407
TI  - Novel generation of agents with proven clinical activity in multiple myeloma.
AB  - The activity observed with proteasome inhibitors and immunomodulatory drugs
      (IMIDs) in multiple myeloma (MM) has prompted the development of second- and
      third-generation agents with similar, but not exactly the same, mechanisms of
      action as their predecessors. This review summarizes the mechanism of action and
      the available data on the clinical activity of novel proteasome inhibitors
      (carfilzomib, oprozomib, ixazomib, and marizomib) and novel IMIDs (pomalidomide),
      stressing the similarities and differences with bortezomib, and with thalidomide
      and lenalidomide, respectively. In summary, these novel agents have shown
      clinical activity as single agents and in combination with dexamethasone, with
      similar or even higher efficacy than their parental drugs; moreover, they may
      even overcome resistance, indicating that there are some differences in their
      mechanisms of action and resistance. These data indicate that both the inhibition
      of the proteasome and the modulation of the immune system are good strategies to
      target MM tumor cells and this, along with the absence of complete cross
      resistance observed among these drugs, open new avenues to optimize their use
      through the most appropriate sequencing and combinations. 

PMID- 24135409
TI  - The future of drug development and therapy in myeloma.
AB  - The treatment options and outcomes for patients with myeloma has dramatically
      improved over the past decade, due in large part to the availability of improved
      anti-myeloma treatments including high-dose therapy, thalidomide, bortezomib, and
      lenalidomide. Many of the currently active agents are effective because of their
      impact on normal plasma cell biology, suggesting that targeting the plasma cell,
      rather than malignant cell biology has led to more effective therapy.
      Additionally, the use of combination therapy, with agents that are synergistic
      when combined, has led to deeper responses, and these have likely also
      contributed to improvements not only in progression free but also overall
      survival. With the wealth of new agents coming into the myeloma space, it is
      incumbent upon us as investigators to utilize efficient study designs with novel
      statistical approaches in order to rapidly test and evaluate new drugs. These
      concepts as well as a few selective promising targets in early development will
      be reviewed in the current discussion. 

PMID- 24135410
TI  - Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in
      Behcet's syndrome patients.
AB  - Behcet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology.
      Features of both innate and adaptive immunity have been claimed in the
      pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin
      (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of
      mutation(s), we performed single-strand conformation polymorphism analyses and/or
      sequencing of all the coding regions and intron-exon boundaries of
      NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD)
      genes from Turkish BS patients and healthy controls. At the same time, we
      determined pro-inflammatory cytokine secretion profiles of peripheral blood cells
      in response to LPS treatment using ELISA. BS patients with vascular involvement
      showed significantly increased levels of TNF-alpha release at 2-, 4- and 8-h post
      treatment and significantly increased IL-1beta levels were detected at 2h (P =
      0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the
      NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but
      none in control samples. No mutations were detected in the ASC gene. The effect
      of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1beta secretion was
      tested and the V200M mutant was shown to induce IL-1beta secretion. Thus, it is
      likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown
      other factors may contribute to the pro-inflammatory cytokine profiles in BS
      patients. 

PMID- 24135408
TI  - Novel agents for multiple myeloma to overcome resistance in phase III clinical
      trials.
AB  - The incorporation of novel agents such as bortezomib and lenalidomide into
      initial therapy for multiple myeloma has improved the response rate of induction
      regimens. Also, these drugs are being increasingly used in the peri-transplant
      setting for transplant-eligible patients, and as part of consolidation and/or
      maintenance after front-line treatment, including in transplant-ineligible
      patients. Together, these and other strategies have contributed to a prolongation
      of progression-free survival (PFS) and overall survival (OS) in myeloma patients,
      and an increasing proportion are able to sustain a remission for many years.
      Despite these improvements, however, the vast majority of patients continue to
      suffer relapses, which suggests a prominent role for either primary, innate drug
      resistance, or secondary, acquired drug resistance. As a result, there remains a
      strong need to develop new proteasome inhibitors and immunomodulatory agents, as
      well as new drug classes, which would be effective in the relapsed and/or
      refractory setting, and overcome drug resistance. This review will focus on novel
      drugs that have reached phase III trials, including carfilzomib and pomalidomide,
      which have recently garnered regulatory approvals. In addition, agents that are
      in phase II or III, potentially registration-enabling trials will be described as
      well, to provide an overview of the possible landscape in the relapsed and/or
      refractory arena over the next 5 years. 

PMID- 24135411
TI  - Comparison of the T2Dx instrument with T2Candida assay and automated blood
      culture in the detection of Candida species using seeded blood samples.
AB  - As a delay in the diagnosis and treatment of candidemia is associated with
      increased mortality and healthcare costs, a more rapid method of detection is
      urgently needed. The T2Candida assay is a new rapid diagnostic test, which uses
      T2 magnetic resonance technology to identify Candida spp. directly from whole
      blood in approximately 3 hours. In this study, the performance of the BACTEC 9050
      using Aerobic Plus/F blood culture bottles was compared to that of the T2Candida
      assay run on the T2Dx Instrument for detection of Candida albicans, Candida
      tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei, in seeded
      blood samples at concentrations between 3.1 and 11 CFU/mL. The BACTEC 9050
      detected Candida growth in 100% of bottles (n = 20 replicates) within 5 days for
      all species (63.23 +/- 30.27 hours), with the exception of Candida glabrata (0%).
      The T2Candida assay had a 100% detection rate for each species (n = 13-20
      replicates) within 3 hours including C. glabrata. The sensitivity and specificity
      of the T2Candida assay were 1 and 0.978, respectively. 

PMID- 24135412
TI  - Evaluation of a new real-time PCR assay (Check-Direct CPE) for rapid detection of
      KPC, OXA-48, VIM, and NDM carbapenemases using spiked rectal swabs.
AB  - To prevent the spread of carbapenemase-producing bacteria, a fast and accurate
      detection of patients carrying these bacteria is extremely important. The Check
      Direct CPE assay (Check-Points, Wageningen, The Netherlands) is a new multiplex
      real-time PCR assay, which has been developed to detect and differentiate between
      the most prevalent carbapenemase genes encountered in Enterobacteriaceae (blaKPC,
      blaOXA-48, blaVIM, and blaNDM) directly from rectal swabs. Evaluation of this
      assay using 83 non-duplicate isolates demonstrated 100% sensitivity and
      specificity and the correct identification of the carbapenemase gene(s) present
      in all carbapenemase-producing isolates. Moreover, the limit of detection (LoD)
      of the real-time PCR assay in spiked rectal swabs was determined and showed
      comparable LoDs with the ChromID CARBA agar. With an excellent performance on
      clinical isolates and spiked rectal swabs, this assay appeared to be an accurate
      and rapid method to detect blaKPC, blaOXA-48, blaVIM, and blaNDM genes directly
      from a rectal screening swab. 

PMID- 24135413
TI  - Emergence of NDM-producing Klebsiella pneumoniae in Greece.

PMID- 24135414
TI  - Nosema adaliae sp. nov., a new microsporidian pathogen from the two-spotted lady
      beetle, Adalia bipunctata L. (Coleoptera: Coccinellidae) and its relationship to
      microsporidia that infect other coccinellids.
AB  - The two-spotted lady beetle, Adalia bipunctata L., is a tree-dwelling lady beetle
      endemic to parts of Europe, Central Asia and North America that is commercially
      available for aphid control in Europe and North America. Lady beetles host a wide
      variety of symbionts including parasitoids, viruses, eugregarines, fungi,
      bacteria, nematodes and microsporidia. Four species of microsporidia have been
      described from lady beetles, and an undescribed microsporidium was recently
      isolated from local populations of A. bipunctata in Nova Scotia, Canada. In a
      previous study, this pathogen prolonged the development of A. bipunctata larvae
      but had no effect on adult fecundity, longevity or sex ratios. The objective of
      this study was to formally describe the microsporidium by means of its
      ultrastructure, tissue pathology and molecular characterization. All stages of
      the microsporidium were diplokaryotic and developed in direct contact with the
      host cell cytoplasm. Mature spores measured 4.25+/-0.09*1.82+/-0.03MUm (SE, n=49,
      from micrographs) and fresh spores measured 6.10+/-0.06*3.01+/-0.05MUm (+/-SE,
      n=60; range: 5.0-6.9*2.18-3.86MUm). The polar filament was isofilar with 10-18
      coils that were frequently arranged in a single row. The lamellar polaroplast was
      not typically visible and spores contained a relatively small posterior vacuole.
      Both the flight muscles and fat body were heavily infected and a large number of
      spores were observed within and between the cells of these tissues. The ovaries,
      developing oocytes, spermatocytes and accessory glands within the testes, midgut
      epithelium, Malpighian tubules, ileum, colon, and ventral nerve cord were also
      infected but not as heavily. Connective tissue near the cuticle and surrounding
      the trachea were lightly infected. The presence of spores in both the alimentary
      canal and ovaries (particularly within developing oocytes) suggests that the
      microsporidium can be transmitted per os (horizontally) and transovarially
      (vertically). Molecular analysis of the genome of the microsporidium described in
      this study was 97% similar to Nosema bombi and 96% similar to Nosema thomsoni,
      Nosema vespula and Nosema oulemae. Based on information gained during this study,
      we propose that the microsporidium in A. bipunctata be given the name Nosema
      adaliae sp. nov. 

PMID- 24135415
TI  - Access to outpatient care for adult rotator cuff patients with private insurance
      versus Medicaid in North Carolina.
AB  - BACKGROUND: Access to orthopaedic care for pediatric patients has been shown in
      previous studies to be decreased for patients with Medicaid compared with those
      with private insurance. The relationship between type of insurance and access to
      care for adult patients with acute rotator cuff tears has not yet been examined.
      This study aimed to determine if type of health insurance would have an impact on
      access to care for an adult patient with an acute rotator cuff tear. METHODS:
      Seventy-one orthopaedic surgery practices within the state of North Carolina were
      randomly selected and contacted on 2 different occasions separated by 3 weeks.
      The practices were presented with an appointment request for a fictitious 42-year
      old man with an acute rotator cuff tear. Insurance status was reported as
      Medicaid for the first call and as private insurance during the second call.
      RESULTS: Of the 71 practices contacted, 51 (72%) offered the patient with
      Medicaid an appointment, whereas 68 (96%) offered the patient with private
      insurance an appointment. The difference in these rates was statistically
      significant (P < .001). The likelihood of patients with private insurance
      obtaining an appointment was 8.8 times higher than that of patients with Medicaid
      (95% CI: 2.5, 31.5). CONCLUSION: For patients with acute rotator cuff tears,
      access to care is decreased for those with Medicaid compared with those with
      private insurance. Patients with private insurance are 8.8 times more likely than
      those with Medicaid to obtain an appointment. LEVEL OF EVIDENCE: Basic science,
      survey study.

PMID- 24135416
TI  - The costs associated with the evaluation of rotator cuff tears before surgical
      repair.
AB  - BACKGROUND: Patients undergoing rotator cuff repair typically have a diagnostic
      evaluation and trial of nonoperative therapy before surgery. Recent studies have
      evaluated the cost-effectiveness of surgery, but none have attempted to estimate
      the costs associated with the preoperative evaluation. This study used available
      data to examine major expenditures during the preoperative period. MATERIALS AND
      METHODS: We conducted a search using an insurance company database to identify
      patients undergoing rotator cuff repair from 2004 to 2009. Patients were
      identified by the common Current Procedural Terminology codes for rotator cuff
      repair. The associated charge codes for the 90-day period before surgery were
      categorized as outpatient physician visits, diagnostic imaging studies,
      injections, physical therapy, laboratory and other preoperative studies, prior
      surgeries, and miscellaneous. The frequency of each code and the associated
      charges were noted. RESULTS: In total, 92,688 patients were identified in the
      study period. A total of $161,993,100 was charged during the preoperative period,
      for an average of $1,748 per patient. Diagnostic imaging charges totaled
      $104,510,646 (65%); injections, $5,145,227 (3%); outpatient visits, $29,723,751
      (18%); physical therapy, $13,844,270 (8.5%); preoperative studies, $6,792,245
      (4.2%); and miscellaneous, $1,164,688 (<1%). CONCLUSIONS: The costs for
      preoperative evaluation of rotator cuff tears are substantial, and the majority
      of the costs are associated with magnetic resonance imaging. To help reduce
      costs, future studies should attempt to identify the factors that predict which
      patients might not respond to nonoperative management and might benefit from
      early surgical intervention. In addition, magnetic resonance imaging should
      perhaps be reserved for patients in whom the diagnosis cannot be achieved by
      other modalities.

PMID- 24135417
TI  - Cost utility analysis of reverse total shoulder arthroplasty.
AB  - BACKGROUND: Reverse shoulder arthroplasty provides satisfactory outcomes, but its
      cost-effectiveness is unproven. We prospectively analyzed outcomes and costs for
      primary reverse shoulder arthroplasty. METHODS: Thirty serial patients (16 women
      and 14 men; mean age, 74.1 years [range, 61.1-87.3 years]) with rotator cuff
      arthropathy had active motion recorded and completed function tests (visual pain
      analog scale; Simple Shoulder Test; American Shoulder and Elbow Surgeons Shoulder
      Outcome score; EuroQol; and Short Form-36 Health Survey) preoperatively and
      postoperatively at 1 and 2 years. Costs included professional fees, operating
      room and supply costs, and hospital care. Changes were compared by the Wilcoxon
      signed rank test, and quality-adjusted life-years were calculated preoperatively
      and postoperatively. RESULTS: Twenty-seven patients completed the study. Clinical
      and functional outcomes demonstrated significant improvement (P < .05).
      Significantly improved (P < .05) Short Form-36 subgroups included physical
      functioning, role limitations due to physical health, bodily pain, vitality, and
      physical composite score. EuroQol dimensions of usual activities and
      pain/discomfort improved significantly (P < .05). Calculations with the SF-6D
      showed that median QALYs improved from 6.56 preoperatively to 7.43 at 1-year
      follow-up (P <.09) and from 6.56 preoperatively to 7.58 at 2-year follow-up (P
      <.003). The increase in QALYs calculated from the EQ-5D was somewhat greater,
      changing from 6.21 preoperatively to 7.69 at 1-year follow-up (P <.0001) and from
      6.13 to 8.10 at 2-year follow-up (P <.04). Mean cost was $21,536. Cost utility at
      2 years was $26,920/quality-adjusted life-year by the Short Form 6 Dimensions and
      $16,747/quality-adjusted life-year by the EuroQol. CONCLUSION: EuroQol and Short
      Form-36 results demonstrated modestly cost-effective (<$50,000/quality-adjusted
      life-year) improvement for cuff tear arthropathy patients after primary reverse
      shoulder arthroplasty. LEVEL OF EVIDENCE: Level II, economic and decision
      analysis.

PMID- 24135418
TI  - Variation in use of reverse total shoulder arthroplasty across hospitals.
AB  - BACKGROUND: The opportunity for variation exists in the choice between anatomic
      and reverse total shoulder arthroplasty. Quality improvement methods seek to
      reduce variation. We used supply-chain data to characterize variation in the
      selection of anatomic versus reverse total shoulder arthroplasty across hospitals
      and to analyze the effect of hospital volume on this variation. METHODS:
      Mendenhall Associates, Inc (Ann Arbor, MI, USA) provided us with a database of
      hospital supply-chain data from orthopaedic surgical cases. This study included
      hospitals in which at least one total shoulder arthroplasty was performed. We
      calculated, for each hospital, the percentages of each type of prosthesis
      implanted and examined the distribution of these percentages across all
      hospitals. We also divided the sample of hospitals into tertiles, by volume of
      total shoulder arthroplasties performed, and examined the distributions of
      percentage reverse shoulder arthroplasty performed in each tertile. RESULTS:
      Across all hospitals, we saw wide variation in the volume of total shoulder
      arthroplasties and the percentage of reverse shoulder arthroplasties performed.
      Hospitals with lower total shoulder arthroplasty volumes exhibited greater
      variation in the percentages of each type of total shoulder arthroplasty
      performed. Higher volume hospitals exhibited smaller variation. CONCLUSIONS: This
      study revealed wide variation in the selection of anatomic and reverse total
      shoulder arthroplasty across all hospitals and an inverse relationship between
      hospital volume and variation. This variation signals uncertainty about the best
      application of each device and that there is need for improvement in the
      consistency of treatment of patients with shoulder disease. LEVEL OF EVIDENCE:
      Level II, cost-effectiveness study, economic and decision analysis.

PMID- 24135419
TI  - Does the latissimus dorsi tendon transfer for massive rotator cuff tears remain
      active postoperatively and restore active external rotation?
AB  - HYPOTHESIS: The purpose of this study is to evaluate the muscle activity with
      surface electromyography (EMG) and the clinical outcome of the latissimus dorsi
      transfer. It remains unclear whether the clinical results of the latissimus dorsi
      transfer for massive posterosuperior rotator cuff tears are achieved either by
      active muscle contractions or by a passive tenodesis effect of the transfer.
      METHODS: Eight patients were evaluated preoperatively and at 1 year (SD, 0.1)
      after the latissimus dorsi transfer. Clinical evaluation of outcomes included
      active range of motion, Constant score, and visual analog scale (VAS) for pain
      and activities of daily living (ADL). Muscle activity was recorded with EMG
      during directional isometric abduction and adduction tasks. RESULTS: The external
      rotation in adduction improved from 23 degrees  to 51 degrees  (P = .03). The
      external rotation in abduction improved from 10 degrees  to 70 degrees  (P =
      .02). The mean Constant score improved from 39 to 62 postoperatively (P = .01).
      The VAS for pain at rest improved from 3.3 preoperatively to 0.1 (P = .02). The
      VAS for ADL improved from 4.9 to 2.3 (P = .05). The transferred latissimus dorsi
      remained active in all cases, as reflected by increased latissimus dorsi EMG
      activity during abduction tasks. In addition, the latissimus dorsi EMG activity
      shifted from preoperative antagonistic co-activation in adduction to synergistic
      activation in abduction. CONCLUSION: The latissimus dorsi has synergistic muscle
      activity after transfer. Apart from a tenodesis effect, directional muscle
      activity seems relevant for improved clinical outcome and pain relief. A specific
      gain was observed for external rotation in elevated arm positions, a motion
      essential for ADL tasks.

PMID- 24135420
TI  - Readmission after shoulder arthroplasty.
AB  - BACKGROUND: Health care payers, including the federal government, increasingly
      base reimbursement on quality. Payers consider readmission rates after total
      joint arthroplasty an indicator of quality. The Patient Protection and Affordable
      Care Act contains provisions that preclude payment of hospital cost associated
      with joint arthroplasty readmissions occurring within 30 days of discharge. This
      study evaluates the readmission rates and the incidence of "never events" after
      inpatient shoulder arthroplasty procedures. METHODS: A retrospective view of all
      shoulder arthroplasty was performed from 2005 to 2011, with specific emphasis on
      the readmission rate 30, 60, and 90 days after the procedure. The incidence of
      never events as defined by the Centers for Medicare and Medicaid Services was
      also analyzed. RESULTS: During the study period, 680 shoulder arthroplasty
      procedures were performed. Overall readmission rate was 5.9%. For
      hemiarthroplasty (HA), total shoulder arthroplasty (TSA), and reverse total
      shoulder arthroplasty (RTSA), 90-day readmission rates were 8.8%, 4.5%, and 6.6%,
      respectively. Readmission rates within 30 days of admission were significantly
      more common for HA and RTSA compared with readmission rates after 30 days. There
      was a 1.0% incidence of never events, and the incidence associated with each of
      the 3 arthroplastic procedures did not differ significantly. CONCLUSION:
      Readmission within the first 90 days after shoulder arthroplasty occurred in 5.9%
      of patients. There was a 1% incidence of never events. In addition, most
      readmissions after HA and RTSA occurred within 30 days of discharge. As health
      care expenditures become more closely scrutinized, readmission rates after
      shoulder arthroplasty will become increasingly important.

PMID- 24135422
TI  - Investigating the sources and potential health risks of environmental
      contaminants in the soils and drinking waters from the rural clusters in Thiva
      area (Greece).
AB  - The present study investigates the possible influence of human activities on
      metal loadings of topsoil in a typical small rural city in central Greece and the
      chemical quality of tap water in surrounding villages. Furthermore, the study
      aimed to examine potential health risks of naturally enriched heavy metals to
      exposed population taking into account the soil and drinking water as exposure
      pathways. The mean concentrations of Ni, Cr, Co, Mn, Pb, Cu, Zn and Cd in the
      soil were 1777, 285, 99, 946, 30, 26, 78 and 0.67 mg/kg respectively. Combination
      of pollution indexes based on local reference background soils and statistical
      analyses (correlation analysis, cluster analysis and principal component
      analysis) revealed that anthropogenic activities have not modified the natural
      soil chemistry at least in a large scale. High Hazard Quotient (HQ) values for
      children were estimated for Ni, Cr and Co based on total metal concentrations for
      the soil ingestion route (9.26E-01, 9.75E-01 and 3.45E+00 respectively). However,
      evaluation of HQs based on published bioaccessible concentrations suggested that
      the population groups would not likely experience potential health risks as a
      result of exposure to contaminated soils. Concentrations of Cr(VI) in tap waters
      were within the allowable limits. However, the risk assessment model revealed
      that local residents (adults) of Eleonas and Neochori villages are at some
      carcinogenic risks considering lifetime ingestion of water (potential cancer
      risks 2.05E-04 and 1.29E-04 respectively). Despite the uncertainties accompanying
      these procedures and the great deal of debate regarding the human carcinogenicity
      of Cr(VI) by the oral route, results of this study drive attention to remediation
      measures that should include epidemiological studies for the local population.

PMID- 24135421
TI  - Treatment choice affects inpatient adverse events and mortality in older aged
      inpatients with an isolated fracture of the proximal humerus.
AB  - BACKGROUND: This study tests the null hypothesis that, among patients aged 65 and
      older admitted to a United States hospital with an isolated fracture of the
      proximal humerus (no other injuries or fractures), there are no differences
      between operative (fixation or arthroplasty) and nonoperative treatments with
      respect to inpatient adverse events, inpatient mortality, and discharge to a long
      term care facility rates accounting for comorbidities. METHODS: Using a large
      national database representing an estimated 132,005 patients aged 65 and older
      admitted to a US hospital with an isolated proximal humerus fracture between 2003
      and 2007. Sixty-one percent did not have surgery, 22% were treated with open
      reduction and internal fixation (ORIF), and 17% were treated with arthroplasty.
      RESULTS: The risk of an in hospital adverse event was 21% overall and was 4.4
      times greater with arthroplasty and 2.7 times greater with ORIF compared to
      nonoperative treatment. The risk of in hospital death was 1.8% overall and was
      2.8 times greater with ORIF compared to nonoperative treatment. Patients treated
      operatively were less likely to be discharged to a long-term facility compared to
      patients treated nonoperatively. CONCLUSION: In spite of a tendency to treat the
      most infirm patients (those that are not discharged to home) nonoperatively,
      operative treatment (open reduction and internal fixation in particular) is an
      independent risk factor for inpatient adverse events and mortality in older-aged
      patients admitted to the hospital with an isolated fracture of the proximal
      humerus and should perhaps be offered more judiciously. LEVEL OF EVIDENCE: Level
      III, retrospective cohort study, treatment study.

PMID- 24135423
TI  - Morphological and biochemical behavior of fenugreek (Trigonella foenum-graecum)
      under copper stress.
AB  - The effects of copper on germination and growth of fenugreek (Trigonella foenum
      graecum) was investigated separately using different concentrations of CuSO4. The
      germination percentage and radical length had different responses to cupric ions:
      the root growth increased with increasing copper concentration up to 1 mM Cu2+
      and was inhibited thereafter. In contrast, the germination percentage was largely
      unaffected by concentrations of copper below 10 mM. The reduction in root growth
      may have been due to inhibition of hydrolytic enzymes such as amylase. Indeed,
      the average total amylolytic activity decreased from the first day of treatment
      with [Cu2+] greater than 1 mM. Furthermore, copper affected various plant growth
      parameters. Copper accumulation was markedly higher in roots as compared to
      shoots. While both showed a gradual decrease in growth, this was more pronounced
      in roots than in leaves and in stems. Excess copper induced an increase in the
      rate of hydrogen peroxide (H2O2) production and lipid peroxidation in all plant
      parts, indicating oxidative stress. This redox stress affected leaf chlorophyll
      and carotenoid content which decreased in response to augmented Cu levels.
      Additionally, the activities of proteins involved in reactive oxygen species
      (ROS) detoxification were affected. Cu stress elevated the ascorbate peroxidase
      (APX) activity more than two times at 10 mM CuSO4. In contrast, superoxide
      dismutase (SOD) and catalase (CAT) levels showed only minor variations, only at 1
      mM Cu2+. Likewise, total phenol and flavonoid contents were strongly induced by
      low concentrations of copper, consistent with the role of these potent
      antioxidants in scavenging ROS such as H2O2, but returned to control levels or
      below at high [Cu2+]. Taken together, these results indicate a fundamental shift
      in the plant response to copper toxicity at low versus high concentrations.

PMID- 24135425
TI  - Clinical application of high-throughput genomic technologies for treatment
      selection in breast cancer.
AB  - Large-scale collaborative initiatives using next-generation DNA sequencing and
      other high-throughput technologies have begun to characterize the genomic
      landscape of breast cancer. These landmark studies have identified infrequent
      driver mutations that are potential targets for therapeutic intervention with
      approved or investigational drug treatments, among other important discoveries.
      Recently, many institutions have launched molecular screening programs that apply
      high-throughput genomic technologies to patients with advanced solid
      malignancies, including breast cancer, to inform clinical decision-making. This
      article provides an overview of the recent molecular insights in breast cancer,
      including potentially actionable somatic alterations, the technological platforms
      currently available in a clinical diagnostics setting to detect these
      alterations, and ongoing institutional or regional molecular screening programs
      in advanced breast cancer.

PMID- 24135426
TI  - Challenges to promoting health in the modern welfare state: the case of the
      Nordic nations.
AB  - AIMS: Finland, Norway, and Sweden are leaders in promoting health through public
      policy action. Much of this has to do with the close correspondence between key
      health promotion concepts and elements of the Nordic welfare state that promote
      equity through universalist strategies and programs that provide citizens with
      economic and social security. The purpose of this article is to identify the
      threats to the Nordic welfare states related to immigration, economic
      globalization, and welfare state fatigue. METHODS: Through a critical analysis of
      relevant literature and data this article provides evidence of the state of the
      Nordic welfare state and some of these challenges to the Nordic welfare state and
      its health promotion efforts. RESULTS: There is evidence of declining support for
      the unconditional Nordic welfare state, increases in income inequality and
      poverty, and a weakening of the programs and supports that have associated with
      the excellent health profile of the Nordic nations. This is especially the case
      for Sweden. CONCLUSIONS: It is argued that the Nordic welfare states'
      accomplishments must be celebrated and used as a basis for maintaining the public
      policies shown to be successful in promoting the health of its citizens.

PMID- 24135427
TI  - Propranolol and infantile hemangiomas: different routes of administration, a
      randomized clinical trial.
AB  - Oral propranolol has become the treatment of choice of infantile hemangiomas
      (IH)s. However, the safety of systemic propranolol is questioned. Topical therapy
      with 1% propranolol has been reported to be safe and effective. Intralesional
      (IL) administration may possibly allow safe delivery of higher drug dosages. AIM:
      To assess the efficacy and safety of two locally administered routes of
      propranolol (topical and IL), in comparison with its systemic oral use in the
      treatment of IHs. PATIENTS AND METHODS: 45 patients with IHs were randomly
      divided into 3 groups, A, B and C (n = 15 in each), receiving oral propranolol, 2
      mg/kg/day, topical propranolol 1% ointment twice daily, IL propranolol, 1 mg of
      propranolol hydrochloride in 1 ml of injection once weekly, respectively. Follow
      up was done for 6 months after treatment was stopped. RESULTS: Excellent response
      was achieved in 9 patients in group A (60%), 3 in group B (20%) and 2 in group C
      (13.3%), (P value : 0.04). As regards safety, all 3 modalities proved safe with
      no major side effects apart from 1 patient in group A and 3 in group C who
      dropped out due to pain or inconvenience of therapy. CONCLUSIONS: Further work is
      needed to establish clear guidelines and reach best formulations. Nevertheless,
      in properly selected patients with IHs, we recommend the usage of oral
      propranolol. Topically administered propranolol could be considered in patients
      at risk of potential side effects from oral administration. As IL application did
      not offer any more benefits, it could not be recommended.

PMID- 24135428
TI  - Echinococcus multilocularis and Echinococcus canadensis in wolves from western
      Canada.
AB  - Echinococcus species are important parasites of wildlife, domestic animals and
      people worldwide; however, little is known about the prevalence, intensity and
      genetic diversity of Echinococcus tapeworms in Canadian wildlife. Echinococcus
      tapeworms were harvested from the intestines of 42% of 93 wolves (Canis lupus)
      from five sampling regions in the Northwest Territories, Manitoba and
      Saskatchewan, and visually identified to genus level by microscopic examination.
      Genetic characterization was successful for tapeworms from 30 wolves, and
      identified both Echinococcus canadensis and Echinococcus multilocularis in all
      sampling locations. Mixed infections of E. canadensis/E. multilocularis, as well
      as the G8/G10 genotypes of E. canadensis were observed. These findings suggest
      that wolves may be an important definitive host for both parasite species in
      western Canada. This represents the first report of wolves naturally infected
      with E. multilocularis in North America, and of wolves harbouring mixed
      infections with multiple species and genotypes of Echinococcus. These
      observations provide important information regarding the distribution and
      diversity of zoonotic species of Echinococcus in western North America, and may
      be of interest from public health and wildlife conservation perspectives.

PMID- 24135424
TI  - Molecular complexes that direct rhodopsin transport to primary cilia.
AB  - Rhodopsin is a key molecular constituent of photoreceptor cells, yet
      understanding of how it regulates photoreceptor membrane trafficking and
      biogenesis of light-sensing organelles, the rod outer segments (ROS) is only
      beginning to emerge. Recently identified sequence of well-orchestrated molecular
      interactions of rhodopsin with the functional networks of Arf and Rab GTPases at
      multiple stages of intracellular targeting fits well into the complex framework
      of the biogenesis and maintenance of primary cilia, of which the ROS is one
      example. This review will discuss the latest progress in dissecting the molecular
      complexes that coordinate rhodopsin incorporation into ciliary-targeted carriers
      with the recruitment and activation of membrane tethering complexes and
      regulators of fusion with the periciliary plasma membrane. In addition to
      revealing the fundamental principals of ciliary membrane renewal, recent advances
      also provide molecular insight into the ways by which disruptions of the
      exquisitely orchestrated interactions lead to cilia dysfunction and result in
      human retinal dystrophies and syndromic diseases that affect multiple organs,
      including the eyes. 

PMID- 24135429
TI  - Putative association of GPC5 polymorphism with the risk of inflammatory
      demyelinating diseases.
AB  - Inflammatory demyelinating diseases (IDDs) are severe inflammatory diseases of
      the central nervous system (CNS) that cause loss of myelin in the nerve sheaths
      and axonal degeneration. IDDs include multiple sclerosis (MS) and neuromyelitis
      optica (NMO). MS affects the axons of the brain and spinal cord, while NMO
      primarily affects the optic nerves and spinal cord. Glypican 5 (GPC5) is known to
      be one of the susceptible genes for the risk of IDD, especially MS, based on
      genome-wide association studies (GWASs) and replication studies in Caucasians and
      African Americans. In the present study, in order to investigate the replicable
      genetic effects of GPC5 polymorphisms on the risk of IDD in Korean subjects, nine
      genetic variants were selected and genotyped in 237 normal controls and 178 IDD
      patients (including 79 MS and 99 NMO). Statistical analysis revealed that
      rs9523762 was associated with IDD and the association was retained even after
      correction for multiple testing (OR=1.68, P(corr)=0.03). Marginal association was
      also observed in rs1411751 (OR=0.54, P=0.02). In a subgroup analysis, rs1411751
      was found to be associated with NMO (OR=0.36, P(corr)=0.03), and rs9523762 was
      marginally associated with both NMO and MS. These results indicate that GPC5
      polymorphisms would be useful genetic indicators for IDDs, including NMO and MS. 

PMID- 24135430
TI  - Symptomatic female carriers of Duchenne muscular dystrophy (DMD): genetic and
      clinical characterization.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by
      mutations in the dystrophin gene and is characterized by muscle degeneration and
      death. DMD affects males; females being asymptomatic carriers of mutations.
      However, some of them manifest symptoms due to a translocation between X
      chromosome and an autosome or to a heterozygous mutation leading to inactivation
      of most of their normal X chromosome. Six symptomatic female carriers and two
      asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to
      detect a hemizygous alteration, and II) X chromosome inactivation pattern to
      uncover the reason for symptoms in these females. The symptomatic females shared
      mild but progressive muscular weakness and increased serum creatin kinase (CK)
      levels. Levels of dystrophin protein were below normal or absent in many fibers.
      Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which
      were confirmed by MLPA. In addition, this analysis showed a duplication in
      another patient. X chromosome inactivation assay revealed a skewed X inactivation
      pattern in the symptomatic females and a random inactivation pattern in the
      asymptomatic ones. Our results support the hypothesis that the DMD phenotype in
      female carriers of a dystrophin mutation has a direct correlation with a skewed X
      chromosome inactivation pattern. 

PMID- 24135431
TI  - Morphologic features and glial activation in rat oxaliplatin-dependent
      neuropathic pain.
AB  - Neurotoxicity is the limiting side effect of the anticancer agent oxaliplatin. A
      tangled panel of symptoms, sensory loss, paresthesia, dysesthesia, and pain may
      be disabling for patients and adversely affect their quality of life. To
      elucidate the morphologic and molecular alterations that occur in the nervous
      system during neuropathy, rats were daily injected with 2.4 mg kg(-1) oxaliplatin
      intraperitoneally. A progressive decrease in the pain threshold and
      hypersensitivity to noxious and nonnoxious stimuli were evidenced during the
      treatment (7, 14, 21 days). On day 21, morphometric alterations were detectable
      exclusively in the dorsal root ganglia, whereas the activating transcription
      factor 3 and neurofilament (heavy-chain) expression changed dramatically in both
      the nerves and ganglia. Inflammatory features were not highlighted.
      Interestingly, satellite cells exhibited signs of activation. Glial modulation
      was characterized in the spinal cord and brain areas involved in pain signaling.
      On the 21st day, spinal astrocytes increased numerically whereas the microglial
      population was unaltered. The number of glial cells in the brain differed
      according to the zone and treatment time points. In particular, on day 21, a
      significant astrocyte increase was measured in the anterior cingulate cortex,
      somatosensory area 1, neostriatum, ventrolateral periaqueductal gray, and nucleus
      raphe magnus. PERSPECTIVES: These data highlight the relevance of glial cells in
      chemotherapy-induced neurotoxicity as part of the investigation of the role that
      specific brain areas play in neuropathy.

PMID- 24135432
TI  - Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients
      with chronic pain.
AB  - Several studies have reported reduced cerebral gray matter (GM) volume or density
      in chronic pain conditions, but there is limited research on the plasticity of
      the human cortex in response to psychological interventions. We investigated GM
      changes after cognitive-behavioral therapy (CBT) in patients with chronic pain.
      We used voxel-based morphometry to compare anatomic magnetic resonance imaging
      scans of 13 patients with mixed chronic pain types before and after an 11-week
      CBT treatment and to 13 healthy control participants. CBT led to significant
      improvements in clinical measures. Patients did not differ from healthy controls
      in GM anywhere in the brain. After treatment, patients had increased GM in the
      bilateral dorsolateral prefrontal, posterior parietal, subgenual anterior
      cingulate/orbitofrontal, and sensorimotor cortices, as well as hippocampus, and
      reduced GM in supplementary motor area. In most of these areas showing GM
      increases, GM became significantly higher than in controls. Decreased pain
      catastrophizing was associated with increased GM in the left dorsolateral
      prefrontal and ventrolateral prefrontal cortices, right posterior parietal
      cortex, somatosensory cortex, and pregenual anterior cingulate cortex. Although
      future studies with additional control groups will be needed to determine the
      specific roles of CBT on GM and brain function, we propose that increased GM in
      the prefrontal and posterior parietal cortices reflects greater top-down control
      over pain and cognitive reappraisal of pain, and that changes in somatosensory
      cortices reflect alterations in the perception of noxious signals. PERSPECTIVE:
      An 11-week CBT intervention for coping with chronic pain resulted in increased GM
      volume in prefrontal and somatosensory brain regions, as well as increased
      dorsolateral prefrontal volume associated with reduced pain catastrophizing.
      These results add to mounting evidence that CBT can be a valuable treatment
      option for chronic pain.

PMID- 24135433
TI  - Pain does not follow the boxcar model: temporal dynamics of the BOLD fMRI signal
      during constant current painful electric nerve stimulation.
AB  - The temporal dynamics of the blood oxygen level-dependent (BOLD) signal,
      especially for painful stimulations, is not completely understood. In this study,
      the BOLD signal response to a long painful electrical stimulation (a continuous
      painful stimulation of 2 minutes) is directly compared to that of a short painful
      stimulation (four 30-second periods of painful stimulation interleaved with 30
      second rest) in an effort to further probe the relationship between the temporal
      dynamics of the BOLD signal during constant-intensity pain stimulation. Time
      course analysis showed that both stimulation protocols produced 3 similarly timed
      peaks in both data sets, suggesting an early and delayed BOLD response to painful
      stimulation initiation, and a response related to stimulus termination. Despite
      the continuous stimulation, the BOLD signal returned to baseline in the 2-minute
      task. Even with this signal discrepancy, however, the activation maps of the 2
      pain tasks differed only slightly, suggesting that the bulk of the activation is
      determined by the sharp rise in BOLD signal with stimulus onset. These findings
      imply that the BOLD signal response time course is not directly reflective of
      pain perception. PERSPECTIVE: This article demonstrates that the BOLD signal for
      a painful stimulation contains multiple peaks and does not maintain the constant
      level during stimulation that is assumed in typical analysis. Although these
      dynamics should be accounted for in future studies because of their ability to
      confound results, their presence did not significantly alter the overall group
      maps.

PMID- 24135434
TI  - A novel otoferlin splice-site mutation in siblings with auditory neuropathy
      spectrum disorder.
AB  - We characterize a novel otoferlin mutation discovered in a sibling pair diagnosed
      with auditory neuropathy spectrum disorder and investigate auditory nerve
      function through their cochlear implants. Genetic sequencing revealed a
      homozygous mutation at the otoferlin splice donor site of exon 28 (IVS28 + 1G>T)
      in both siblings. Functional investigation showed that the intronic sequence
      between exons 28 and 29 was retained in the mutated minigenes that were expressed
      in 293T cells. Auditory nerve compound action potential recovery functions in the
      siblings demonstrated different rates of neural recovery, with sibling AN1
      showing rapid recovery (1.14 ms) and AN2 showing average recovery (0.78 ms)
      compared to subjects with sensorineural hearing loss (average: adults 0.71 ms,
      children 0.85 ms). Differences in neural recovery were consistent with speech
      perception differences between the siblings. Genotype information may indicate
      site of lesion in hearing loss; however, additional, as yet, unknown factors may
      impact clinical outcomes and must be considered.

PMID- 24135435
TI  - Dose or content? Effectiveness of pain rehabilitation programs for patients with
      chronic low back pain: a systematic review.
AB  - We sought to systematically analyze the influence of dose of pain rehabilitation
      programs (PRPs) for patients with chronic low back pain (CLBP) on disability,
      work participation, and quality of life (QoL). Literature searches were performed
      in PubMed, Cochrane Library, Cinahl, and Embase up to October 2012, using MeSH
      terms, other relevant terms and free-text words. Randomized controlled trials in
      English, Dutch, and German, analyzing the effect of PRPs, were included. One of
      the analyzed interventions had to be a PRP. Outcomes should be reported regarding
      disability, work participation, or QoL. To analyze dose, the number of contact
      hours should be reported. Two reviewers independently selected titles, abstracts,
      and full-text articles on the basis of inclusion and exclusion criteria. Data
      were extracted and risk of bias was assessed. Effect sizes (ES) were calculated
      for each intervention, and influence of dose variables was analyzed by a mixed
      model analysis. Eighteen studies were identified, reporting a wide variety of
      dose variables and contents of PRPs. Analyses showed that evaluation moment,
      number of disciplines, type of intervention, duration of intervention in weeks,
      percentage of women, and age influenced the outcomes of PRPs. The independent
      effect of dose variables could not be distinguished from content because these
      variables were strongly associated. Because dose variables were never studied
      separately or reported independently, we were not able to disentangle the
      relationship between dose, content, and effects of PRPs on disability, work
      participation, and QoL. 

PMID- 24135436
TI  - Correlation between protoporphyrin IX fluorescence intensity, photobleaching,
      pain and clinical outcome of actinic keratosis treated by photodynamic therapy.
AB  - BACKGROUND: Photodynamic therapy (PDT) with Metvix(r) is a good therapeutic
      option to treat actinic keratosis, but it presents drawbacks (pain, lesion
      recurrences, heterogeneous outcome), emphasizing the possible need to
      individualize treatment. OBJECTIVE: We assessed whether PDT clinical outcome and
      pain during treatment were correlated with protoporphyrin IX fluorescence
      intensity and photobleaching. METHODS: 25 patients were treated by Metvix PDT.
      The outcome was evaluated after 1.3 (+/-0.4), 7.6 (+/-1.8), 13.2 (+/-1.2) and
      33.6 (+/-3.0) months. After administration of Metvix, red light (632 +/- 10 nm)
      was delivered with a light-emitting diode panel device. The outcome was assessed
      on a cosmetoclinical scale. RESULTS: All patients who showed a fluorescence level
      before PDT treatment above a certain threshold had a complete recovery at 33.6
      (+/-3.0) months. CONCLUSION: Our approach could be used to individualize PDT
      treatment based on the pretreatment fluorescence level, and to predict its long
      term outcome.

PMID- 24135438
TI  - What's in a name?

PMID- 24135437
TI  - A prospective pilot study of (89)Zr-J591/prostate specific membrane antigen
      positron emission tomography in men with localized prostate cancer undergoing
      radical prostatectomy.
AB  - PURPOSE: In this pilot study we explored the feasibility of (89)Zr labeled J591
      monoclonal antibody positron emission tomography of localized prostate cancer.
      MATERIALS AND METHODS: Before scheduled radical prostatectomy 11 patients were
      injected intravenously with (89)Zr-J591, followed 6 days later by whole body
      positron emission tomography. Patients underwent surgery the day after imaging.
      Specimens were imaged by ex vivo micro positron emission tomography and a custom
      3 Tesla magnetic resonance scanner coil. Positron emission tomography images and
      histopathology were correlated. RESULTS: Median patient age was 61 years (range
      47 to 68), median prostate specific antigen was 5.2 ng/ml (range 3.5 to 12.0) and
      median biopsy Gleason score of the 11 index lesions was 7 (range 7 to 9). On
      histopathology 22 lesions were identified. Median lesion size was 5.5 mm (range 2
      to 21) and median Gleason score after radical prostatectomy was 7 (range 6 to 9).
      Eight of 11 index lesions (72.7%) were identified by in vivo positron emission
      tomography. Lesion identification improved with increasing lesion size for in
      vivo and ex vivo positron emission tomography (each p <0.0001), and increasing
      Gleason score (p = 0.14 and 0.01, respectively). Standardized uptake values
      appeared to correlate with increased Gleason score but not significantly (p =
      0.19). CONCLUSIONS: To our knowledge this is the first report of (89)Zr
      J591/prostate specific membrane antigen positron emission tomography in localized
      prostate cancer cases. In this setting (89)Zr-J591 bound to tumor foci in situ
      and positron emission tomography identified primarily Gleason score 7 or greater
      and larger tumors, likely corresponding to clinically significant disease
      warranting definitive therapy. A future, larger clinical validation trial is
      planned to better define the usefulness of (89)Zr-J591 positron emission
      tomography for localized prostate cancer.

PMID- 24135439
TI  - Fungal prostatitis caused by coccidioides.

PMID- 24135440
TI  - Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a
      cost-effectiveness analysis.
AB  - BACKGROUND: Glutaric aciduria type I (GA-I) is a rare metabolic disorder caused
      by inherited deficiency of glutaryl-CoA dehydrogenase. Despite high prognostic
      relevance of early diagnosis and start of metabolic treatment as well as an
      additional cost saving potential later in life, only a limited number of
      countries recommend newborn screening for GA-I. So far only limited data is
      available enabling health care decision makers to evaluate whether investing into
      GA-I screening represents value for money. The aim of our study was therefore to
      assess the cost-effectiveness of newborn screening for GA-I by tandem mass
      spectrometry (MS/MS) compared to a scenario where GA-I is not included in the
      MS/MS screening panel. METHODS: We assessed the cost-effectiveness of newborn
      screening for GA-I against the alternative of not including GA-I in MS/MS
      screening. A Markov model was developed simulating the clinical course of
      screened and unscreened newborns within different time horizons of 20 and 70
      years. Monte Carlo simulation based probabilistic sensitivity analysis was used
      to determine the probability of GA-I screening representing a cost-effective
      therapeutic strategy. RESULTS: Within a 20 year time horizon, GA-I screening
      averts approximately 3.7 DALYs (95% CI 2.9 - 4.5) and about one life year is
      gained (95% CI 0.7 - 1.4) per 100,000 neonates screened initially . Moreover, the
      screening programme saves a total of around 30,682 Euro (95% CI 14,343 to 49,176
      Euro) per 100,000 screened neonates over a 20 year time horizon. CONCLUSION:
      Within the limitations of the present study, extending pre-existing MS/MS newborn
      screening programmes by GA-I represents a highly cost-effective diagnostic
      strategy when assessed under conditions comparable to the German health care
      system.

PMID- 24135441
TI  - Treatment satisfaction in renal transplant patients taking tacrolimus once daily.
AB  - BACKGROUND: Adherence to immunosuppressive therapy, which is important to prevent
      rejection after organ transplantation, is influenced by satisfaction of patients
      with their medication regimen. OBJECTIVE: We investigated the effect of
      introducing a simplified medication regimen for renal transplant patients on
      treatment satisfaction, in particular, convenience. METHODS: In a prospective
      cohort study, treatment was switched from tacrolimus twice daily to tacrolimus
      once daily with a simultaneous change to a once-daily formulation of other drugs
      when applicable. Treatment satisfaction was measured in 75 participants with the
      validated Treatment Satisfaction Questionnaire for Medication version II.
      RESULTS: The treatment convenience score increased from a mean (SD) of 66.0
      (14.5) to 78.5 (14.5) (P < 0.001). The mean (SD) daily number of medication
      ingestion time points diminished from 2.4 (0.7) to 1.6 (0.7) (P < 0.001), and the
      mean (SD) daily number of tablets decreased from 12.4 (3.3) to 9.1 (2.6) (P <
      0.001). The self-reported adherence to the medication regimen increased from
      79.7% to 94.6% (P < 0.001). CONCLUSIONS: The introduction of a simplified
      medication regimen enabled by the use of a once-daily formulation of tacrolimus
      increases treatment convenience after renal transplantation. This regimen had a
      beneficial effect on self-reported adherence.

PMID- 24135442
TI  - Association of plasma concentration of 4beta-hydroxycholesterol with CYP3A5
      polymorphism and plasma concentration of indoxyl sulfate in stable kidney
      transplant recipients.
AB  - Several studies have shown that renal failure decreases CYP3A activity and that
      uremic toxins may play a role via transcriptional or translational modifications
      of cytochrome P450 (P450) enzymes and direct inhibition of P450-mediated
      metabolism. In this study, we evaluated the relationship between CYP3A activity
      (using plasma concentration of 4beta-hydroxycholesterol as a biomarker) and
      clinical characteristics including plasma concentrations of indoxyl sulfate (3
      INDS) and indole-3-acetic acid (3-IAA) in stable kidney transplant recipients.
      Forty-five Japanese kidney transplant recipients who underwent transplantation
      more than 90 days prior to the study were included. Morning blood samples were
      collected and plasma concentrations of 4beta-hydroxycholesterol, 3-INDS, and 3
      IAA were measured. Plasma concentrations of 4beta-hydroxycholesterol were 57.1 +/
      11.2, 42.1 +/- 11.8, and 34.5 +/- 7.3 ng/ml in recipients with CYP3A5*1/*1 (n =
      5), *1/*3 (n = 15), and *3/*3 (n = 25) genotypes, respectively, with significant
      differences between three genotypes. A significant correlation was observed
      between plasma concentrations of 4beta-hydroxycholesterol and 3-INDS but not 3
      IAA. Multiple regression analysis identified the number of CYP3A5*3 alleles in
      genotype, plasma concentration of 3-INDS, and body weight as independent
      variables associated with plasma concentration of 4beta-hydroxycholesterol. In
      conclusion, these results suggest that CYP3A5 polymorphism and plasma
      concentration of 3-INDS may account for the interindividual variability of CYP3A
      activity, and that plasma concentration of 3-INDS may partially explain the gap
      in CYP3A activity that cannot be explained by genetic contribution in patients
      with renal failure. 

PMID- 24135443
TI  - Evaluating the impact of comprehensive epilepsy education programme for school
      teachers in Chandigarh city, India.
AB  - PURPOSE: School teachers can play a key role in the first-aid management of
      school children experiencing a seizure. The teachers have a pivotal role in
      disseminating knowledge to the children of diseases experienced by them and
      developing positive attitudes among the children regarding the diseases. The
      present study investigated the knowledge and practices used by teachers to manage
      epileptic seizures. The study also tested an epilepsy intervention educational
      package to see whether it improved the knowledge and practices of the teachers
      regarding epilepsy. METHODS: A total of 85 teachers in schools from Chandigarh, a
      city of northern India, participated in the study. At the start of the study the
      teachers completed a pre-tested, semi-structured questionnaire on the first-aid
      management of epileptic seizures. They were then presented with an intervention
      package that included audio-visual material on basic aspects of epilepsy. The
      teachers were then retested after the intervention (one immediately and another
      after three months from the intervention). A scoring system was devised to
      quantify the knowledge, attitude and skills of teachers. RESULTS: More than 90%
      of the teachers had previously either heard or read about epilepsy. Nearly half
      of the teachers said that books and magazines were the most common source of
      their information, followed by the internet. A comparison of the knowledge,
      attitudes and skills about the first-aid management of epilepsy based on the
      before and after questionnaire scores showed significant improvements in the
      various domains (p<0.05). CONCLUSION: The epilepsy intervention educational
      package provided a positive, short term, impact on the knowledge and skills of
      teachers about epilepsy. There is a need for regular workshops to improve and
      reinforce the knowledge and skills of the teachers about health problems like
      epilepsy.

PMID- 24135444
TI  - Encephalopathy with electrical status epilepticus during sleep: cognitive and
      executive improvement after epilepsy surgery.

PMID- 24135445
TI  - Structural and functional analysis of PUR2,5 gene encoding bifunctional enzyme of
      de novo purine biosynthesis in Ogataea (Hansenula) polymorpha CBS 4732T.
AB  - We describe the cloning, sequencing and functional characterization of gene
      PUR2,5, involved in de novo purine biosynthesis of the yeast Ogataea (Hansenula)
      polymorpha. This gene (2369 bp) was cloned by genetic complementation of adenine
      requiring mutation. It encodes a bifunctional enzyme of 789 amino acids (85 kDa)
      that catalyzes the second and the fifth steps of de novo purine biosynthesis
      pathway and shows dual enzymatic activity - of glycinamide ribotide synthetase
      (GARS, EC 6.3.4.13) and of aminoimidazole ribotide synthetase (AIRS, EC 6.3.3.1).
      Nucleotide sequence analysis revealed the presence of putative regulatory
      elements located in the adjacent 5' region. Canonical motives that function as
      binding sites for BAS1 transcription activator were found at positions (-593) and
      (-389). The putative TAATTA-box was located at (-20) to (-14) and AT-rich
      heteroduplex was found in the 3'-non-translated region. We compared the amino
      acid sequence of OpPUR2,5p with those of the corresponding enzymes of other yeast
      species as well as with distant organisms like bacteria Escherichia coli and
      human Homo sapiens. A successful disruption of OpPUR2,5 gene was done. It was
      found that OpPUR2,5::LEU2 replacement affects both mating and sporulation
      processes. OpPUR2,5 sequence is deposited in the GenBank of NCBI with accession
      no. JF967633.

PMID- 24135446
TI  - Using the CHADS2 and CHA2DS2-VASc scores for stroke risk prediction as well as
      the identification of stroke outcomes and cardiac complications in patients with
      and without atrial fibrillation.

PMID- 24135447
TI  - A case of spontaneous intracranial hypotension presenting as isolated permanent
      neck pain.

PMID- 24135448
TI  - Different pharmacological effects of progestins should be considered when applied
      in traumatic brain injury patients.

PMID- 24135449
TI  - Treatment of pyoderma gangrenosum with topical factor XIII.
AB  - Pyoderma gangrenosum (PG) is a severe ulcerative skin disease. Despite systemic
      immunosuppressive therapy, PG ulcers often progress and can develop into life
      threatening conditions. In this case series, we treated 6 patients suffering from
      recalcitrant PG with topical coagulation factor XIII, which has been shown to
      exert beneficial effects on tissue regeneration and wound healing. All 6 patients
      showed a positive response to treatment with a marked reduction in wound size
      that was maintained during a 3-month follow-up period. The treatment was well
      tolerated with no remarkable adverse effects or complications. Topical factor
      XIII has potential in combination with standard immunosuppressive therapy for the
      treatment of PG. 

PMID- 24135450
TI  - ReVeaLD: a user-driven domain-specific interactive search platform for biomedical
      research.
AB  - Bioinformatics research relies heavily on the ability to discover and correlate
      data from various sources. The specialization of life sciences over the past
      decade, coupled with an increasing number of biomedical datasets available
      through standardized interfaces, has created opportunities towards new methods in
      biomedical discovery. Despite the popularity of semantic web technologies in
      tackling the integrative bioinformatics challenge, there are many obstacles
      towards its usage by non-technical research audiences. In particular, the ability
      to fully exploit integrated information needs using improved interactive methods
      intuitive to the biomedical experts. In this report we present ReVeaLD (a Real
      time Visual Explorer and Aggregator of Linked Data), a user-centered visual
      analytics platform devised to increase intuitive interaction with data from
      distributed sources. ReVeaLD facilitates query formulation using a domain
      specific language (DSL) identified by biomedical experts and mapped to a self
      updated catalogue of elements from external sources. ReVeaLD was implemented in a
      cancer research setting; queries included retrieving data from in silico
      experiments, protein modeling and gene expression. ReVeaLD was developed using
      Scalable Vector Graphics and JavaScript and a demo with explanatory video is
      available at http://www.srvgal78.deri.ie:8080/explorer. A set of user-defined
      graphic rules controls the display of information through media-rich user
      interfaces. Evaluation of ReVeaLD was carried out as a game: biomedical
      researchers were asked to assemble a set of 5 challenge questions and time and
      interactions with the platform were recorded. Preliminary results indicate that
      complex queries could be formulated under less than two minutes by unskilled
      researchers. The results also indicate that supporting the identification of the
      elements of a DSL significantly increased intuitiveness of the platform and
      usability of semantic web technologies by domain users. 

PMID- 24135451
TI  - An increased number of CD4+CD25+ cells induced by an oral administration of
      Lactobacillus plantarum NRIC0380 are involved in antiallergic activity.
AB  - BACKGROUND: Our previous study showed that an oral administration of
      Lactobacillus plantarum NRIC0380 inhibited immunoglobulin E (IgE) production in a
      murine model, and that orally administered NRIC0380 induced CD4+CD25+ Foxp3+ T,
      i.e. regulatory T (Treg), cells in the spleen and Peyer's patch of mice. Although
      it has been reported that Treg cells might suppress the allergic symptoms, the
      involvement of the cells in the antiallergic activity of lactic acid bacteria has
      not been clearly demonstrated. We therefore examined in detail the antiallergic
      activity of Treg cells obtained from mice that had been fed NRIC0380. METHODS:
      Treg cells were obtained from mice that had been fed NRIC0380. The T cell
      suppressive effect of the cells was analyzed by coculturing the cells with
      splenocytes of beta-lactoglobulin-immunized mice and beta-lactoglobulin. The
      effects of the Treg cells on the IgE production and cutaneous anaphylaxis
      reaction were then analyzed by transferring the cells into another mouse.
      RESULTS: The Treg cells obtained from the mice that had been fed NRIC0380 showed
      similar T cell-suppressive activity to those cells obtained from the control
      mice. The Treg cells obtained from the mice fed NRIC0380 significantly inhibited
      the IgE production and active cutaneous anaphylaxis reaction when transferred
      into another mouse that was subsequently immunized with the antigen. Furthermore,
      the Treg cells also significantly suppressed the passive cutaneous anaphylaxis
      reaction when cotransferred with the IgE antibody into another mouse.
      CONCLUSIONS: The induction of Treg cells by the oral administration of NRIC0380
      would be involved in the antiallergic activity of NRIC0380.

PMID- 24135452
TI  - Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate
      for human ABC transporter ABCB1.
AB  - The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to
      produce guanidine alkaloids as well as bioactive flavonols such as kaempferol,
      quercetin, and rutin. In the present study, we examined the possibility of
      interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four
      guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A,
      pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell
      line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT
      assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared
      to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of
      cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three
      of the four guanidine alkaloids were found to stimulate the ATPase activity of
      ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity
      of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic
      effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by
      verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the
      present study, the possibility of interaction between ABCB1 and two synthetic
      nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into
      the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The
      ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced
      by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in
      nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine
      alkaloids from P. nitens dock to the same binding pocket as verapamil.
      Nitensidine A and its analogs exhibit similar binding energies to verapamil.
      Taken together, this research clearly indicates that nitensidine A is a novel
      substrate for ABCB1. The present results also suggest that the number, binding
      site, and polymerization degree of the isoprenyl moiety in the guanidine
      alkaloids and the imino nitrogen atom cooperatively contribute to their
      stimulation of ABCB1's ATPase activity. 

PMID- 24135453
TI  - Selective adsorption of L1210 leukemia cells/human leukocytes on micropatterned
      surfaces prepared from polystyrene/polypropylene-polyethylene blends.
AB  - The objective of this study is to prepare polymeric surfaces which will adsorb
      L1210 leukemia cells selectively more than that of healthy human leukocytes in
      order to develop new treatment options for people with leukemia. Chemically
      heterogeneous and micropatterned surfaces were formed on round glass slides by
      dip coating with accompanying phase-separation process where only commercial
      polymers were used. Surface properties were determined by using optical
      microscopy, 3D profilometry, SEM and measuring contact angles. Polymer,
      solvent/nonsolvent types, blend composition and temperature were found to be
      effective in controlling the dimensions of surface microislands. MTT tests were
      applied for cell viability performance of these surfaces.
      Polystyrene/polyethylene-polypropylene blend surfaces were found to show
      considerable positive selectivity to L1210 leukemia cells where L1210/healthy
      leukocytes adsorption ratio approached to 9-fold in vitro. Effects of
      wettability, surface free energy, microisland size geometry on the adsorption
      performances of L1210/leukocytes pairs are discussed. 

PMID- 24135454
TI  - The impact of milk proteins and peptides on blood pressure and vascular function:
      a review of evidence from human intervention studies.
AB  - CVD are the leading cause of death worldwide. Hypertension, a major controllable
      risk factor of CVD, is intimately associated with vascular dysfunction, a defect
      which is also now recognised to be a major, modifiable risk factor for the
      development of CVD. The purpose of the present review was to critically evaluate
      the evidence for the effects of milk proteins and their associated peptides on
      blood pressure (BP) and vascular dysfunction. After a detailed literature search,
      the number of human trials evaluating the antihypertensive effects of casein
      derived peptides (excluding isoleucine-proline-proline and valine-proline
      proline) was found to be limited; the studies were preliminary with substantial
      methodological limitations. Likewise, the data from human trials that examined
      the effects of whey protein and peptides were also scarce and inconsistent. To
      date, only one study has conducted a comparative investigation on the relative
      effects of the two main intact milk proteins on BP and vascular function. While
      both milk proteins were shown to reduce BP, only whey protein improved measures
      of arterial stiffness. In contrast, a growing number of human trials have
      produced evidence to support beneficial effects of both milk proteins and
      peptides on vascular health. However, comparison of the relative outcomes from
      these trials is difficult owing to variation in the forms of assessment and
      measures of vascular function. In conclusion, there is an accumulating body of
      evidence to support positive effects of milk proteins in improving and/or
      maintaining cardiovascular health. However, the variable quality of the studies
      that produced this evidence, and the lack of robust, randomised controlled
      intervention trials, undermines the formulation of firm conclusions on the
      potential benefits of milk proteins and peptides on vascular health. 

PMID- 24135455
TI  - Transcriptional profile of genes involved in oxidative stress and antioxidant
      defense in PC12 cells following treatment with cerium oxide nanoparticles.
AB  - BACKGROUND: Thanks to their impressive catalytic properties, cerium oxide
      nanoparticles (nanoceria) are able to mimic the activity of superoxide dismutase
      and of catalase, therefore acting as reactive oxygen species (ROS) scavengers in
      many biological contexts, for instance offering neuroprotection and reduction of
      apoptosis rate in many types of cells exposed to oxidative stress (stem cells,
      endothelial cells, epithelial cells, osteoblasts, etc.). METHODS: We report on
      the investigation at gene level, through quantitative real time RT-PCR, of the
      effects of cerium oxide nanoparticles on ROS mechanisms in neuron-like PC12
      cells. After three days of treatment, transcription of 84 genes involved in
      antioxidant defense, in ROS metabolism, and coding oxygen transporters is
      evaluated, and its relevance to central nervous system degenerative diseases is
      considered. RESULTS: Experimental evidences reveal intriguing differences in
      transcriptional profiles of cells treated with cerium oxide nanoparticles with
      respect to the controls: nanoceria acts as strong exogenous ROS scavenger,
      modulating transcription of genes involved in natural cell defenses, down
      regulating genes involved in inflammatory processes, and up-regulating some genes
      involved in neuroprotection. CONCLUSIONS: Our findings are extremely promising
      for future biomedical applications of cerium oxide nanoparticles, further
      supporting their possible exploitation in the treatment of neurodegenerative
      diseases. GENERAL SIGNIFICANCE: This work represents the first documented step to
      the comprehension of mechanisms underlying the anti-oxidant action of cerium
      oxide nanoparticles. Our findings allow for a better comprehension of the
      phenomena of ROS scavenging and neuroprotection at a gene level, suggesting
      future therapeutic approaches even at a pre-clinical level.

PMID- 24135457
TI  - Emphysematous pyelonephritis: patient characteristics and management approach.
AB  - INTRODUCTION: Emphysematous pyelonephritis (EPN) is an acute, severe, necrotizing
      infection of the renal parenchyma and perirenal tissue that requires immediate
      treatment. However, the ideal approach to its management remains controversial.
      We conducted this study to determine the appropriate treatment modalities.
      MATERIALS AND METHODS: A retrospective review of EPN cases revealed 10
      consecutive cases from July 2003 to June 2012. Clinical and demographic data were
      collected from each patient. RESULTS: All patients had diabetes mellitus, 5
      presented with urinary tract obstruction by urolithiasis. Seven patients had type
      I disease and 3 had type II disease. Six of the type I patients underwent
      emergent nephrectomy and 1 of these died, the remaining patient refused surgical
      intervention and died after receiving medical management only. The type II
      patients underwent percutaneous drainage, and 2 of them subsequently underwent
      elective nephrectomy; all 3 survived. CONCLUSION: Our results suggest that
      emergency nephrectomy may be considered the initial management for type I EPN,
      while percutaneous drainage may be an effective initial treatment option for type
      II EPN.

PMID- 24135456
TI  - Photodamage of lipid bilayers by irradiation of a fluorescently labeled cell
      penetrating peptide.
AB  - BACKGROUND: Fluorescently labeled cell-penetrating peptides can translocate into
      cells by endocytosis and upon light irradiation, lyse the endocytic vesicles.
      This photo-inducible endosomolytic activity of Fl-CPPs can be used to efficiently
      deliver macromolecules such as proteins and nucleic acids and other small organic
      molecules into the cytosol of live cells. The requirement of a light trigger to
      induce photolysis provides a more spatial and temporal control to the
      intracellular delivery process. METHODS: In this report, we examine the molecular
      level mechanisms by which cell-penetrating peptides such as TAT when labeled with
      small organic fluorophore molecules acquire a photo-induced lytic activity using
      a simplified model of lipid vesicles. RESULTS: The peptide TAT labeled with 5(6)
      carboxytetramethylrhodamine binds to negatively charged phospholipids, thereby
      bringing the fluorophore in close proximity to the membrane of liposomes. Upon
      light irradiation, the excited fluorophore produces reactive oxygen species at
      the lipid bilayer and oxidation of the membrane is achieved. In addition, the
      fluorescent peptide causes aggregation of photo-oxidized lipids, an activity that
      requires the presence of arginine residues in the peptide sequence. CONCLUSIONS:
      These results suggest that the cell-penetrating peptide plays a dual role. On one
      hand, TAT targets a conjugated fluorophore to membranes. On the other hand, TAT
      participates directly in the destabilization of photosensitized membranes.
      Peptide and fluorophore therefore appear to act in synergy to destroy membranes
      efficiently. GENERAL SIGNIFICANCE: Understanding the mechanism behind Fl-CPP
      mediated membrane photodamage will help to design optimally photo-endosomolytic
      compounds.

PMID- 24135458
TI  - Prevalence of prediabetes and newly diagnosed diabetes in patients with a
      transient ischemic attack or stroke.
AB  - BACKGROUND: Patients with a transient ischemic attack (TIA) or stroke and
      prediabetes or newly diagnosed diabetes are at high risk of recurrent stroke or
      cardiovascular events. This underlines the importance of accurate screening for
      impaired glucose metabolism in clinical practice. Fasting plasma glucose levels
      are currently the most commonly measured glycemic parameter to detect prediabetes
      or diabetes, even if 2-hour postload glucose and glycosylated hemoglobin levels
      can be used as well. We assessed the prevalence of prediabetes and newly
      diagnosed diabetes with different screening methods, including fasting plasma
      glucose, 2-hour postload glucose and glycosylated hemoglobin levels in
      consecutive patients with recent TIA, ischemic stroke or intracerebral hemorrhage
      admitted to the stroke unit or visiting the specialized TIA outpatient clinic in
      the Erasmus Medical Center, Rotterdam, The Netherlands. METHODS: We measured
      fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin
      levels in 269 patients with a TIA, 374 with ischemic stroke and 57 with
      intracerebral hemorrhage, all without a history of diabetes mellitus. Prediabetes
      was defined as fasting plasma glucose levels of 5.6-6.9 mmol/l and/or 2-hour
      postload glucose levels of 7.8-11.0 mmol/l and/or glycosylated hemoglobin levels
      of 5.7-6.4%. Newly diagnosed diabetes was defined as fasting plasma glucose
      levels of >=7.0 mmol/l and/or 2-hour postload levels of >=11.1 mmol/l and/or
      glycosylated hemoglobin levels of >=6.5%. The diagnosis was based on a one-time
      measurement. RESULTS: Based on fasting plasma glucose, 2-hour postload glucose
      and glycosylated hemoglobin levels combined, 365 patients (52%) were identified
      as prediabetics and 188 (27%) as having newly diagnosed diabetes. Patients with
      intracerebral hemorrhage had more often newly diagnosed diabetes compared with
      patients with an ischemic stroke or a TIA [27 (47%) and 161 (25%), respectively;
      p < 0.001]; the prevalence of prediabetes was similar. Newly diagnosed diabetes
      was identified more frequently by 2-hour postload glucose levels (n = 162; 23%)
      than by fasting plasma glucose (n = 49; 7%) or glycosylated hemoglobin levels (n
      = 36; 5%). About one third of the patients with normal fasting glucose levels has
      impaired glucose tolerance or elevated glycosylated hemoglobin levels.
      CONCLUSIONS: Prediabetes and newly diagnosed diabetes are highly prevalent in
      patients with a TIA or stroke. The majority of these patients would not have been
      identified by fasting plasma glucose levels alone. Both 2-hour postload glucose
      and glycosylated hemoglobin levels identify more patients with a disturbed
      glucose metabolism.

PMID- 24135459
TI  - Synthesis, angiopreventive activity, and in vivo tumor inhibition of novel
      benzophenone-benzimidazole analogs.
AB  - AIM: The development of anticancer drugs with specific targets is of prime
      importance in modern biology. This study investigates the angiopreventive and in
      vivo tumor inhibition activities of novel synthetic benzophenone-benzimidazole
      analogs. MAIN METHODS: The multistep synthesis of novel benzophenone
      benzimidazole analogs (8a-n) allowing substitution with methoxy, methyl and
      halogen groups at different positions on the identical chemical backbone and the
      variations in the number of substituents were synthesized and characterized. The
      newly synthesized compounds were further evaluated for cytotoxic and
      antiproliferative effects against Ehrlich ascites carcinoma (EAC) cells. The
      potent lead compounds were further assessed for antiangiogenic effects in a CAM
      model and a tumor-induced vasculature in vivo model. The effect of
      angioprevention on tumor growth was verified in a mouse model. KEY FINDINGS: The
      cytotoxicity studies revealed that compounds 8f and 8n are strongly cytotoxic.
      Analyzing the structure-activity relationship, we found that an increase in the
      number of methyl groups in addition to methoxy substitution at the para position
      of the benzoyl ring in compound 8n resulted in higher potency compared to 8f.
      Furthermore, neovessel formation in in vivo systems, such as the chorioallantoic
      membrane (CAM) and tumor-induced mice peritoneum models, was significantly
      suppressed and reflected the tumor inhibition observed in mice. SIGNIFICANCE:
      These results suggest the potential clinical application of compound 8n as an
      antiangiogenic drug for cancer therapy.

PMID- 24135460
TI  - Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol
      induced gastric lesions in rats.
AB  - AIMS: Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates,
      with recently demonstrated significant pharmacological activities, were assayed
      for their possible overall effect on intact gastric mucosa and their protective
      properties towards the onset of gastric lesions induced by diclofenac (a non
      steroidal anti-inflammatory drug, NSAID) or ethanol. MAIN METHODS: The influence
      of I and M on gastric mucosa integrity was assessed by oral administration in
      doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and
      200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models
      in rats. After the treatment, the stomachs of the animals were analyzed (captured
      by a digital camera). Ulcer scoring, morphometric and histopathological analyses
      of the stomachs were done. KEY FINDINGS: The oral application of these compounds
      on their own, even in quite high doses (200mg/kg) did not induce gastric lesions.
      Both alkaloids exerted a very strong antiulcer activity, even in low doses
      (50mg/kg), by decreasing the number of lesions caused by the application of
      either diclofenac or ethanol, eliminating them completely or reducing them to a
      form of mucosal hyperemia. SIGNIFICANCE: Their possible mechanism of action was
      discussed and due to their many positive properties including anxiolytic,
      antidepressant, antinociceptive, anti-inflammatory and gastroprotective
      activities, as well as a cheap and simple synthetic route for their preparation,
      methyl and isopropyl N-methylanthranilates, both alike, might represent a cost
      effective alternative sought for in the treatment of peptic ulcers and/or new
      safer NSAIDs for pain management.

PMID- 24135461
TI  - Rates of ED visits and of intubations for congestive heart failure declined from
      1996 to 2008.
AB  - OBJECTIVE: Many advances have been made recently in the treatment of congestive
      heart failure (CHF). We hypothesize that this should have resulted in fewer CHF
      patients presenting to the emergency department (ED) and fewer being intubated.
      DESIGN: Retrospective cohort. SETTING: consecutive patients seen by ED physicians
      in 4 suburban hospitals in New Jersey and New York from 1996 to 2008. OBJECTIVE: 
      PROTOCOL: We classified patients as having CHF based on International
      Classification of Diseases, Ninth Revision, codes. For each year of the study, we
      determined CHF visit rates (as a percentage of total ED visits) and calculated
      the percentage of CHF patients intubated. We used the Student t test, calculated
      95% confidence intervals (CIs), and performed regression analyses. RESULTS: Of
      the 2,374,428 ED visits, 32,036 (1.3%) were for CHF. The mean age of the CHF
      patients was 76 +/- 14 years, and 57% were female. Congestive heart failure
      visits declined from 1.6% of all ED visits in 1996 to 1.2% in 2008, a 26%
      relative decrease (95% CI: 21%-30%, P < .001, correlation coefficient R(2) =
      0.94, P < .001). Of the CHF patients, 778 (2.4%) were intubated. Intubation rates
      declined from 3.6% in 1996 to 1.7% in 2008, a 53% (95% CI: 31%-68%, P < .001,
      R(2) = 0.83, P < .001) relative decrease. CONCLUSION: The rates of annual ED
      visits for CHF and intubation rates declined from 1996 to 2008. These decreases
      are most likely due to better CHF treatments.

PMID- 24135462
TI  - Serum concentration of eperisone hydrochloride correlates with QT interval.
AB  - BACKGROUND: Eperisone hydrochloride is a centrally acting muscle relaxant
      prescribed for muscle stiffness that acts by depressing the activities of alpha
      and gamma efferent neurons in the spinal cord and supraspinal structures.
      Although a case of eperisone-induced severe QT prolongation had been reported,
      the relationship between serum eperisone concentration and QT interval remains
      obscure. OBJECTIVE: The aim of this study was to investigate the relationship
      between serum eperisone concentration and QT interval. METHODS: Four patients who
      overdosed on eperisone were admitted to our hospital between January 2010 and
      December 2011. We took simultaneous serial measurements of serum eperisone
      concentration and QT interval in the intensive care unit. In total, 22
      measurement points were plotted for these patients. We analyzed the correlation
      between the serum eperisone concentration and corrected QT (QTc) interval.
      RESULTS: Three men and one woman (mean age, 50 years) overdosed on eperisone with
      an average dose of 3087.5 mg (therapeutic dose, 150 mg/day). The mean QTc
      interval at arrival was 592 ms (range, 444-825 ms), and the mean serum eperisone
      concentration at arrival was 1257.5 ng/mL (range, 14.5-4120.0 ng/mL). The
      correlation coefficient was 0.833 between serum eperisone concentration and QTc
      interval (P < .001). CONCLUSION: Serum eperisone concentration correlates with
      QTc interval in patients who overdose on eperisone.

PMID- 24135463
TI  - Effects of lersivirine on canine and rodent thyroid function.
AB  - Lersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) being
      developed for the treatment of HIV-1 infection. Like other NNRTIs, lersivirine is
      a potent enzyme inducer in rodents capable of inducing a number of hepatic
      enzymes including those involved in its own metabolism. Preclinically lersivirine
      has been associated with hepatocellular hypertrophy and thyroid gland follicular
      cell hypertrophy in rats, mice, and dogs. In rodents, we show that development of
      thyroid hypertrophy is related to the classic mechanism, namely increased
      thyroxine (T4) clearance secondary to induction of uridine
      diphosphoglucuronosyltransferase (UDPGT) in the liver and a resulting increase in
      thyroid-stimulating hormone. Similarly, lersivirine-exposed dogs exhibit a
      significant increase in hepatic UDPGT enzyme activity along with increased T4
      clearance although clear effects on serum thyroid hormone levels were less
      apparent. These effects on thyroid hormonal clearance in the dog suggest that
      thyroid gland hypertrophy in this species is due to the same mechanism shown to
      occur in rodents although, as expected, dogs better adapt to these effects and
      therefore maintain relatively normal thyroid hormonal balance. It is also notable
      that the minimal thyroid follicular hypertrophy that occurs in dogs does not
      progress as is seen in rodents. As is the case with rodents, these adaptive
      changes in the dog are not considered indicative of a human health risk. 

PMID- 24135465
TI  - Type of vascular access and survival among very elderly hemodialysis patients.
AB  - The use of central venous catheters (CVC) for hemodialysis (HD) is associated
      with higher mortality compared to arteriovenous access (AV). However, studies
      analyzing the influence of the type of vascular access on the survival of very
      elderly patients (>=75 years) initiating HD are few and involve only a limited
      number of patients. We studied a cohort of 5,466 incident patients who started
      HD; of these, 1,841 were aged >=75. Types of vascular access for HD were
      classified as either CVC, which included both tunneled and non-tunneled
      catheters, or AV, which included AV fistula and grafts. The outcome of the study
      was all-cause mortality during the follow-up period. In the whole cohort, AV use
      was associated with a survival advantage over CVC use (88 and 63% at 2 and 5
      years, respectively, in patients with an AV as compared to 75 and 48% in patients
      with a CVC) (p < 0.0001). Among patients >=75, CVC use was associated with a
      higher number of deaths compared to AV use. Patients >=75 with an AV showed a
      greater survival as compared to patients >=75 with a CVC (80 and 53% at 2 and 5
      years, respectively, vs. 68 and 43%; p < 0.0001). Multivariate analysis revealed
      that CVC use and the presence of arrhythmia were independent risk factors of
      death in patients >=75, whereas obesity was associated with greater survival. In
      conclusion, the type of vascular access has a significant influence on the
      survival of very elderly patients (>=75) initiating HD. CVC use was associated
      with poorer survival compared to AV access.

PMID- 24135466
TI  - Serum and skin levels of miR-369-3p in patients with psoriasis and their
      correlation with disease severity.
AB  - BACKGROUND: Psoriasis is a common autoimmune skin disease, characterized by
      intense proliferation and abnormal differentiation of keratinocytes. Recently,
      some miRNAs have been proven to show aberrant expression in psoriasis and play a
      role in the pathogenesis of the disease. OBJECTIVES: The aim of this study was to
      detect serum and skin miR-369-3p levels in patients with psoriasis and confirm
      their correlation with disease severity. The regulatory mechanism between miR-369
      3p and TNF-alpha was also investigated. METHODS: Bioinformatics analysis for
      target genes of miRNAs was performed using multiple prediction software. Serum
      samples and skin tissues were collected and serum and skin miR-369-3p levels were
      measured. The Psoriasis Area Severity Index scores of patients and the
      correlation with serum and skin miR-369-3p levels were evaluated. Transient
      transfection and Elisa were applied to HaCaT cells to testify the relationship
      between expression of miR-369-3p and TNF-alpha. RESULTS: Serum and skin miR-369
      3p levels were both higher in patients with psoriasis than those in healthy
      controls (P<0.05; P<0.001, respectively). And miR-369-3p levels in skin had a
      positive linear relation with PASI scores in psoriasis patients (r = 0.70,
      P<0.05). Unexpectedly, miR-369-3p failed to show a regulatory effect on TNF-alpha
      levels in HaCaT cells. CONCLUSIONS: The expression of miR-369-3p is increased in
      both serum samples and skin tissues from psoriasis patients, and its level in the
      skin positively correlates with disease severity. Further studies are needed to
      clarify the role of miR-369-3p in the pathogenesis of psoriasis.

PMID- 24135467
TI  - Perirectal Burkitt lymphoma presenting as an uncommon cause of lower
      gastrointestinal bleeding.

PMID- 24135464
TI  - Subsite awareness in neuropathology evaluation of National Toxicology Program
      (NTP) studies: a review of select neuroanatomical structures with their
      functional significance in rodents.
AB  - This review article is designed to serve as an introductory guide in neuroanatomy
      for toxicologic pathologists evaluating general toxicity studies. The article
      provides an overview of approximately 50 neuroanatomical subsites and their
      functional significance across 7 transverse sections of the brain. Also reviewed
      are 3 sections of the spinal cord, cranial and peripheral nerves (trigeminal and
      sciatic, respectively), and intestinal autonomic ganglia. The review is limited
      to the evaluation of hematoxylin and eosin-stained tissue sections, as light
      microscopic evaluation of these sections is an integral part of the first-tier
      toxicity screening of environmental chemicals, drugs, and other agents. Prominent
      neuroanatomical sites associated with major neurological disorders are noted.
      This guide, when used in conjunction with detailed neuroanatomic atlases, may aid
      in an understanding of the significance of functional neuroanatomy, thereby
      improving the characterization of neurotoxicity in general toxicity and safety
      evaluation studies. 

PMID- 24135468
TI  - Gastric mucosal calcinosis: a rare cause of bleeding.

PMID- 24135471
TI  - [Textual research on 5 words of disease in chu jian (bamboo slips of Chu State)
      of the Warring States Period].
AB  - There are not a few words of disease in the unearthed chu jian (bamboo slips of
      Chu State) of the Warring States Period. The morphology, pronunciation and
      meaning among these characters are completed. By collecting the diseases in the
      equivocally deciphered words, this article comprehensively discusses the words
      among them. It is claimed that in Geling jian (Geling slips), "Xie" is pronounced
      as xie, and "Xie disease" refers to the pain below the oxter and above the waist;
      "Bei", pronounced as jian, and "Bei Pi disease" refers to the pain of the
      shoulder and back;"Jie" reads as jie and refers to scabies; "Du" pronounced as
      fu, and "Du disease" refers to distending pain of the skin. In Wangshan jian
      (Wangshan slips), "Du" is equal to "Du", and is the same as "Du" in baoshan jian
      (baoshan bamboo slips), pronounced as du, refers to exacerbation of disease. 

PMID- 24135470
TI  - Sources and transport of As, Cu, Cd and Pb in the environmental compartments of
      Deception Island, Antarctica.
AB  - Sources and transport processes of As, Cu, Cd and Pb were studied in different
      environmental compartments of Deception Island, an active volcano in the South
      Shetland Islands, Antarctica. Element concentrations in fresh water samples are
      consistent with the lowest values reported elsewhere in Antarctica.
      Interestingly, higher concentration values of As were found in samples collected
      in or near spring water courses and its transport may be related with processes
      of lixiviation in underground waters. While in saline waters Cu and Pb had
      important punctual sources, concentration values for Cd were consistently high
      pointing to the existence of a natural and diffuse source possibly related with
      the hydrothermal activity. The high Si/Al ratio, low carbon content, and a non
      significant anthropogenic heavy metal input may explain the surprisingly
      homogeneous heavy metal content found in sediment samples. 

PMID- 24135472
TI  - [The physicians' recognition and treatment of hypochondriac pain before the Ming
      Dynasty].
AB  - There were two phases for the recognition and treatment of hypochondriac pain
      before the Ming Dynasty, and the Song Dynasty being their demarcation line.
      Before the Song Dynasty, hypochondriac pain was regarded generally as a
      concomitant symptom, generally attributed to pathogen of coldness, and the
      materia medica with the warm nature were always used for the treatment. This
      recognition was related with the traditional idea paying attention predominantly
      to the yang of the yin-yang theory. Since the Song Dynasty, especially the Jin
      Yuan Period, the hypochondriac pain was regarded gradually as an independent
      symptom. Physicians got more and more recognition about its causes and
      pathogenesis. The treatment was changed from dispelling cold to activating qi,
      and the idea of treatment based on syndrome differentiation on hypochondriac pain
      was finally established, reflecting the influence of spirit of medical innovation
      during the Jin-Yuan Period on the recognition of disease. 

PMID- 24135473
TI  - [Research on the origins and development of the verse "eighteen antagonism" in
      Chinese material medica].
AB  - The verse "eighteen antagonism" of Chinese materia medica is a kind of describing
      of drug nature concerning the incompatibility of drugs in compound prescription.
      Through organizing the medical books in different historical periods, it is found
      that the drugs in this verse basically coming from TAO Hong-jing's ben cao jing
      ji zhu (Variorum of Shennong's Classic of Materia Medica), while the style of
      verse mostly appeared during the Song-Jin-Yuan period was made. The formed verse
      was explained and supplemented further in the Ming Dynasty, the basis of which
      appeared in the Song-Jin-Yuan Dynasty, resulting in the increase of the number of
      antagonistic drugs and lengthy verse. The origin of the verse seen in Ru men shi
      qin (Confucians' Duties to Their Parents) and those in other books was not
      identical and was the most popular one after the Qing Dynasty, becoming the most
      popularly known even today. 

PMID- 24135474
TI  - [The prevalence, prevention and treatment of cattle epidemic during the Han-Tang
      Period].
AB  - About 21 times of cattle epidemic with rather strong infectivity happened during
      the Han-Tang Period, including 6 in the Eastern Han Dynasty, 2 in the Jin
      Dynasty, 4 in the Southern and Northern Dynasties, 8 in the Tang Dynasty and 1in
      the Five Dynasty. Most of them were spread along the Yellow River and the
      northern region of the Huai River. The type of cattle epidemic included the acute
      cattle plague, cattle bovine mange, cattle yellow fever and cattle rotten hoof
      disease, etc. Its occurrence and prevalence brought a serious influentce on the
      society of the Han and Tang Dynasties, causing massive mortality of farm cattle,
      and then the shortage of animal power, and threatening the agriculture, which
      drew the attention of the governments, physicians, agriculturists, astrologists
      and Taoists. The medical measures and economic measures were adopted for the
      prevention and treatment of cattle epidemic. Especially, prescriptions in the
      books of medicine and agriculture exerted positive effects on the containment of
      cattle epidemic. On the other hand, its prevalence and the mass mortality of farm
      cattle, in a way, promoted, to certain extent, the improvement of the
      government's function of relief, the updating of the methods of agriculture and
      the creation of new farm tools, and being regarded as a main cause for the
      technological innovation of agriculture. 

PMID- 24135475
TI  - [The people's mentality confronting plague in the Ming Dynasty].
AB  - The social influence of plague was not only confined to its pathogenicity, but
      also its close relationship with the people's mentality. According to the
      historical materials of the Ming Dynasty, there were 2 kinds of mentalities when
      confronting with the prevalence of plague: negative and positive. The former
      included fear, helplessness, depression and superstition etc., and the latter
      included intelligence, consolation, thanksgiving and vigour etc. The negative
      passive mentality didn't help to fight effectively against the plague, or might
      even aggravate its prevalence. However, the positive mentality helped ameliorate
      and control the plague, and also the rehabilitation of the order of production
      and living order after the plague. 

PMID- 24135476
TI  - [The prevalence of epidemic diseases in Inner Mongolia region and the social
      vicissitude of Mongolian ethnic group].
AB  - Since modern times, due to the natural environment, medical and health
      conditions, living habits and other reasons, the diseases were prevalent in the
      region of Inner Mongolia, including fulminating infectious diseases like plague;
      chronic diseases like syphilis, trachoma; along with many common chronic
      disorders like stomach disease and rheumatism etc. The high incidence of some of
      these diseases in Inner Mongolia region, especially plague and venereal diseases,
      greatly affected the growth of the population of Mongolian ethnic group in modern
      times, and also seriously hindered the development of social economy in this
      region. 

PMID- 24135477
TI  - [Exploring the opium prohibition campaign led by LIN Ze-xu, a medical
      perspective].
AB  - Opium destruction in Humen, a feat of the national hero, LIN Ze-xu turned a new
      page of modern history of China. In the past researches, the campaign always
      basically studied under a political historical background. In fact, it was also
      related closely to medicine. During the reign of the Dao Guang Emperor of the
      Qing Dynasty, there was always mentioning of the risk of doping opium and its
      addiction process and mechanism in his serial reports and letters to the imperial
      government. During this inhibition process, he took measures, such as providing
      the medicines to conquer the addiction of opium, asking the effective
      prescriptions for prohibiting opium from physicians and strove to popularize
      them. As viewed from a medical and historical perspective, the opium prohibition
      campaign led by LIN Ze-xu still reveals some enlightening significance even for
      the current society. 

PMID- 24135478
TI  - [Research on the academic genealogy of physiology in modern China].
AB  - The Department of Physiology in Peking Union Medical College was the earliest,
      largest and most authoritative educational and research organization, and played
      a significant role in the development of physiology in modern China. The
      physiology in China entered a new developmental stage, especially after LIN Ke
      sheng (K.K.S.Lim), the founder of modern Chinese physiology, the professor and
      taking the director of the Department in 1925. 14 physiologists, including
      Academician WANG Zhijun, FENG Depei et al. were the second-generation inheritors.
      The third-generation successors included 18 physiologists, with academician CHEN
      Yi-zhang, HAN Ji-sheng as the representatives. The academic genealogy of the
      Department promoted the formation of scientific community of modern physiology,
      laid down a good foundation for the further development of physiology, and had
      far-reaching implications for the institutionalization and academic development
      of modern Chinese physiology. 

PMID- 24135479
TI  - [Textual research on the editions of Ben cao fa ming (Invention of Materia
      Medica)].
AB  - The edition of Ben cao fa ming (Invention of Materia Medica) included in Zhong
      guo ben cao quan shu (The Complete Collection of Traditional Texts on Chinese
      Materia Medica) is photoprinted from the Ming-dynasty block-printed edition
      persevered in the Library of China Academy of Chinese Medical Sciences (CACMS),
      an incomplete one with some parts missing. In addition, there are the Ming
      dynasty block-printed edition preserved in the Shanghai Library and Japanese hand
      copied edition, both complete ones with full texts. In fact, the Shanghai edition
      and CACMS edition are the same one, only the text of "the differential
      classification of ben cao of the Ming Dynasty" are located in different position
      between them. The Japanese one is hand-copied from the Ming-dynasty block-printed
      edition. 

PMID- 24135480
TI  - [Textual research on the edition of WU Kun's books].
AB  - WU Kun is a famous physician of the Xin'an School. He wrote a 6-volume Yi fang
      kao (Textual Research on Recipes) in 1584, a 24-volume Wu zhu su wen (Wu's
      Annotation of Plain Questions) in 1594, a 6-volume Zhen fang liu ji (Six
      Collections of Acupuncture and Prescription) in 1618 block-printed and funded by
      CHENG Biao, and a 2-volume Mai yu (Language of Pulse) with writing date unknown.
      For Yi fang kao, there were 4 editions, including Ming-dynasty block-printed
      edition, Japanese and Korean block-printed edition, old hand-copied edition and
      modern printing edition. For Wu zhu su wen, there were 5 editions, Ming-Qing
      dynasty block-printed edition, Japanese block-printed edition, old hand-copied
      edition, photocopy and modern edition. For Zhen fang liu ji, there were Ming
      dynasty block-printed edition, hand-copied edition, photocopy and modern edition.
      Mai yu always was printed together with Yi fang kao, and its editions were same
      as those of Yi fang kao, except some modern printing edition with Mai yu
      excluded. 

PMID- 24135481
TI  - A wireless and sensitive detection of octachlorostyrene using modified AuNPs as
      signal-amplifying tags.
AB  - A wireless, remote query octachlorostyrene (OCS) biosensor was fabricated by
      coating a mass-sensitive magnetoelastic ribbon with anti-OCS antibody. In
      response to a time-varying magnetic field, the magnetoelastic sensor mechanically
      vibrates at a characteristic resonance frequency which inversely depends on the
      sensor mass loading. As the magnetoelastic film is magnetostrictive itself, the
      vibrations launch magnetic flux that can be remotely detected using a pickup
      coil. Au nanoparticles (NPs) were used to amplify the mass loading. In a sample
      solution containing OCS target and OCS-modified AuNPs (OCS-AuNPs), both OCS and
      OCS-AuNPs react with the anti-OCS antibody immobilized on the sensor surface in a
      competition mode. The bound OCS-AuNPs amount is inversely proportional to the OCS
      target concentration. The reduction of bound OCS-AuNPs induced by free OCS
      results in significant change in mass loading, which amplifies the responses. The
      biosensor demonstrates a linear shift in resonance frequency with OCS
      concentration between 7.4 MUM and 9 nM, with a detection limit of 2.8 nM.

PMID- 24135482
TI  - Prospective randomized comparison of retroperitoneoscopic pyelolithotomy versus
      percutaneous nephrolithotomy for solitary large pelvic kidney stones.
AB  - OBJECTIVES: We performed a prospective randomized comparison of
      retroperitoneoscopic pyelolithotomy (RP) versus percutaneous nephrolithotomy
      (PNL) for solitary pelvic stones >3 cm and assessed the outcome results. METHODS:
      From 2010 to 2012, 44 patients with a solitary pelvic stone >3 cm without any
      anatomical abnormality were randomized to either RP or PNL on a 1:1 ratio. Stone
      free rate, number of procedures per patient and complications were recorded.
      RESULTS: The stone-free rate on the first postoperative day was 95.5% in the RP
      group versus 72.7% in the PNL group (p = 0.04). The stone-free rates at 3 months
      were similar between the two groups. Blood loss, visual pain analog score and
      analgesic requirement on the first postoperative day were significantly higher in
      the PNL group whereas the mean operative time and overall complications were
      similar between the two groups. CONCLUSION: In patients with solitary large
      pelvic stones, RP is associated with lesser blood loss, postoperative pain and
      analgesia as well as with a higher stone-free rate in the immediate postoperative
      period in comparison to PNL. However, the stone clearance rate remains the same
      at 3 months in both groups.

PMID- 24135483
TI  - Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress
      mediated intestinal mucosal injury and inflammation in zebrafish.
AB  - Dysregulated phosphatidylinositol (PI) signaling has been implicated in human
      gastrointestinal (GI) malignancies and inflammatory states, underlining the need
      to study pathophysiological roles of PI in an in vivo genetic model. Here, we
      study the significance of PI in GI pathophysiology using the zebrafish mutant
      cdipt(hi559), which lacks PI synthesis, and unravel a crucial role of PI in
      intestinal mucosal integrity and inflammation. The cdipt(hi559) mutants exhibit
      abnormal villous architecture and disorganized proliferation of intestinal
      epithelial cells (IECs), with pathologies reminiscent of inflammatory bowel
      disease (IBD), including apoptosis of goblet cells, abnormal mucosecretion,
      bacterial overgrowth and leukocyte infiltration. The mutant IECs exhibit
      vacuolation, microvillus atrophy and impaired proliferation. The cdipt(hi559)
      gene expression profile shows enrichment of acute phase response signaling, and
      the endoplasmic reticulum (ER) stress factors hspa5 and xbp1 are robustly
      activated in the mutant GI tissue. Temporal electron micrographic analyses reveal
      that PI-deficient IECs undergo sequential ER-Golgi disruption, mitochondrial
      depletion, macroautophagy and cell death, consistent with chronic ER-stress
      mediated cytopathology. Furthermore, pharmacological induction of ER stress by
      inhibiting protein glycosylation or PI synthase inhibition in leukocyte-specific
      reporter lines replicates the cdipt(hi559) inflammatory phenotype, suggesting a
      fundamental role of PI metabolism and ER stress in mucosal inflammation.
      Antibiotics and anti-inflammatory drugs resolved the inflammation, but not the
      autophagic necroapoptosis of IECs, suggesting that bacterial overgrowth can
      exacerbate ER stress pathology, whereas persistent ER stress is sufficient to
      trigger inflammation. Interestingly, the intestinal phenotype was partially
      alleviated by chemical chaperones, suggesting their therapeutic potential. Using
      zebrafish genetic and pharmacological models, this study demonstrates a newly
      identified link between intracellular PI signaling and ER-stress-mediated mucosal
      inflammation. The zebrafish cdipt mutants provide a powerful tool for dissecting
      the fundamental mechanisms of ER-stress-mediated human GI diseases and a platform
      to develop molecularly targeted therapies. 

PMID- 24135484
TI  - The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro
      and in developing zebrafish.
AB  - DNM2 is a ubiquitously expressed GTPase that regulates multiple subcellular
      processes. Mutations in DNM2 are a common cause of centronuclear myopathy, a
      severe disorder characterized by altered skeletal muscle structure and function.
      The precise mechanisms underlying disease-associated DNM2 mutations are
      unresolved. We examined the common DNM2-S619L mutation using both in vitro and in
      vivo approaches. Expression of DNM2-S619L in zebrafish led to the accumulation of
      aberrant vesicular structures and to defective excitation-contraction coupling.
      Expression of DNM2-S619L in COS7 cells resulted in defective BIN1-dependent
      tubule formation. These data suggest that DNM2-S619L causes disease, in part, by
      interfering with membrane tubulation. 

PMID- 24135485
TI  - Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic
      differentiation in a zebrafish model of fetal valproate syndrome.
AB  - Fetal valproate syndrome (FVS) is caused by in utero exposure to the drug sodium
      valproate. Valproate is used worldwide for the treatment of epilepsy, as a mood
      stabiliser and for its pain-relieving properties. In addition to birth defects,
      FVS is associated with an increased risk of autism spectrum disorder (ASD), which
      is characterised by abnormal behaviours. Valproate perturbs multiple biochemical
      pathways and alters gene expression through its inhibition of histone
      deacetylases. Which, if any, of these mechanisms is relevant to the genesis of
      its behavioural side effects is unclear. Neuroanatomical changes associated with
      FVS have been reported and, among these, altered serotonergic neuronal
      differentiation is a consistent finding. Altered serotonin homeostasis is also
      associated with autism. Here we have used a chemical-genetics approach to
      investigate the underlying molecular defect in a zebrafish FVS model. Valproate
      causes the selective failure of zebrafish central serotonin expression. It does
      so by downregulating the proneural gene ascl1b, an ortholog of mammalian Ascl1,
      which is a known determinant of serotonergic identity in the mammalian brainstem.
      ascl1b is sufficient to rescue serotonin expression in valproate-treated embryos.
      Chemical and genetic blockade of the histone deacetylase Hdac1 downregulates
      ascl1b, consistent with the Hdac1-mediated silencing of ascl1b expression by
      valproate. Moreover, tonic Notch signalling is crucial for ascl1b repression by
      valproate. Concomitant blockade of Notch signalling restores ascl1b expression
      and serotonin expression in both valproate-exposed and hdac1 mutant embryos.
      Together, these data provide a molecular explanation for serotonergic defects in
      FVS and highlight an epigenetic mechanism for genome-environment interaction in
      disease. 

PMID- 24135486
TI  - The basal ganglia in perceptual timing: timing performance in Multiple System
      Atrophy and Huntington's disease.
AB  - The timing of perceptual events depends on an anatomically and functionally
      connected network comprising basal ganglia, cerebellum, pre-frontal cortex and
      supplementary motor area. Recent studies demonstrate the cerebellum to be
      involved in absolute, duration-based timing, but not in relative timing based on
      a regular beat. Conversely, functional involvement of the striatum is observed in
      relative timing, but its role in absolute timing is unclear. This work tests the
      specific role of the basal ganglia in the perceptual timing of auditory events.
      It aims to distinguish the hypothesised unified model of time perception (Teki,
      Grube, & Griffiths, 2012), in which the striatum is a mandatory component for all
      timing tasks, from a modular system in which they subserve relative timing, with
      absolute timing processed by the cerebellum. Test groups comprised individuals
      with Multiple System Atrophy, a disorder in which similar pathology can produce
      clinical deficits associated with dysfunction of the cerebellum (MSA-C, n = 8) or
      striatum (MSA-P, n = 10), and early symptomatic Huntington's disease (HD, n =
      14). Individuals with chronic autoimmune peripheral neuropathy (n = 11) acted as
      controls. Six adaptive tasks were carried out to assess perceptual thresholds for
      absolute timing through duration discrimination for sub- and supra-second time
      intervals, and relative timing through the detection of beat-based regularity and
      irregularity, detection of a delay within an isochronous sequence, and the
      discrimination of sequences with metrical structure. All three patient groups
      exhibited impairments in performance in comparison with the control group for all
      tasks, and severity of impairment was significantly correlated with disease
      progression. No differences were demonstrated between MSA-C and MSA-P, and the
      most severe impairments were observed in those with HD. The data support an
      obligatory role for the basal ganglia in all tested timing tasks, both absolute
      and relative, as predicted by the unified model. The results are not compatible
      with models of a brain timing network based upon independent modules.

PMID- 24135487
TI  - Adiponectin is associated with dynamic hyperinflation and a favourable response
      to inhaled glucocorticoids in patients with COPD.
AB  - OBJECTIVES: Adipokines are protein mediators first described as products of
      adipose tissue regulating energy metabolism and appetite. Recently, adipokines
      have also been found to modulate inflammation and smooth muscle cell responses.
      Therefore we investigated the association of two adipokines, adiponectin and
      leptin, with the degree of emphysema, pulmonary function, symptoms and
      glucocorticoid responsiveness in patients with COPD. METHODS: Plasma adiponectin
      and leptin levels, spirometry, body plethysmography and symptoms were measured in
      43 male COPD patients with smoking history >= 20 pack-years, post bronchodilator
      FEV1/FVC < 0.7 and pulmonary emphysema on HRCT. The measurements were repeated in
      a subgroup of patients after 4 weeks' treatment with inhaled fluticasone.
      RESULTS: In patients with COPD, plasma adiponectin levels correlated positively
      with airway resistance (Raw) (r = 0.362, p = 0.019) and functional residual
      capacity (FRC) (r = 0.355, p = 0.046). Furthermore, the baseline adiponectin
      concentration correlated negatively with the fluticasone induced changes in St
      George's Respiratory questionnaire (SGRQ) symptom score (r = -0.413, p = 0.040)
      and in FRC % pred (r = -0.428, p = 0.003), i.e. a higher baseline plasma
      adiponectin level was associated with more pronounced alleviation of symptoms and
      dynamic hyperinflation. Plasma leptin levels were not related to the measures of
      lung function, symptoms or glucocorticoid responsiveness. CONCLUSIONS: Plasma
      adiponectin levels were associated with peripheral airway obstruction and dynamic
      hyperinflation in patients with COPD. A higher adiponectin level predicted more
      favourable relief of symptoms and hyperinflation during glucocorticoid treatment.
      Adiponectin may have a role in the COPD pathogenesis; it may also be a biomarker
      of disease severity and treatment responses in this disease.

PMID- 24135488
TI  - Resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma: from
      the patient's bed to molecular mechanisms.
AB  - The introduction of anti-angiogenic drugs especially tyrosine kinase inhibitors
      (TKIs) was a breakthrough in the treatment of renal cell carcinoma (RCC).
      Although TKIs have significantly improved outcome in patients with metastatic
      disease, the majority still develop resistance over time. Because different
      combinations and sequences of TKIs are tested in clinical trials, resistance
      patterns and mechanisms underlying this phenomenon should be thoroughly
      investigated. From a clinical point of view, resistance occurs either as a
      primary phenomenon (intrinsic) or as a secondary phenomenon related to various
      escape/evasive mechanisms that the tumor develops in response to vascular
      endothelial growth factor (VEGF) inhibition. Intrinsic resistance is less common,
      and related to the primary redundancy of available angiogenic signals from the
      tumor, causing unresponsiveness to VEGF-targeted therapies. Acquired resistance
      in tumors is associated with activation of an angiogenic switch which leads to
      either upregulation of the existing VEGF pathway or recruitment of alternative
      factors responsible for tumor revascularization. Multiple mechanisms can be
      involved in different tumor settings that contribute both to evasive and
      intrinsic resistance, and current endeavor aims to identify these processes and
      assess their importance in clinical settings and design of pharmacological
      strategies that lead to enduring anti-angiogenic therapies. 

PMID- 24135489
TI  - Screening for diabetes after stroke and transient ischemic attack.

PMID- 24135490
TI  - Characterization of the cytosolic distribution of priority pollutant metals and
      metalloids in the digestive gland cytosol of marine mussels: seasonal and spatial
      variability.
AB  - Cytosolic profiles of several priority pollutant metals (Cu, Cd, Zn, Pb) and
      metalloid As were analyzed in the digestive gland of the mussel (Mytilus
      galloprovincialis) sampled at locations with different environmental pollution
      levels along the Croatian coast in the spring and summer season. Size-exclusion
      chromatography (SEC) connected to inductively coupled plasma mass spectrometry
      (ICP-MS) was used to determine selected elements bound to cytosolic biomolecules
      separated based on their molecular size. Copper, cadmium and zinc eluted mostly
      associated with high molecular weight (HMW) and medium molecular weight (MMW)
      biomolecules, but with a more prominent elution in the MMW peak at polluted
      locations which were probably associated with the 20 kDa metallothionein (MT).
      Elution of all three metals within this peak was also strongly correlated with
      cytosolic Cd as strong inducer of MT. Lead mostly eluted in HMW biomolecule
      range, but in elevated cytosolic Pb concentrations, significant amount eluted in
      low molecular weight (LMW) biomolecules. Arsenic, on the other hand eluted almost
      completely in LMW range, but we could not distinguish specific molecular weight
      biomolecules which would be predominant in detoxification mechanism. Seasonal
      variability in element abundance within specific peaks was present, although not
      in the same extent, for all elements and locations, especially for As. The
      results confirm the suitability of the distribution of selected metals/metalloids
      among different cytosolic ligands as potential indicator for metal exposure.
      Obtained findings can also serve as guidelines for further separation and
      characterization of specific cytosolic metal-binding biomolecules.

PMID- 24135491
TI  - Potential environmental implications of emerging organic contaminants in Taihu
      Lake, China: comparison of two ecotoxicological assessment approaches.
AB  - In this study, the hazard quotient (HQ) and a novel enhanced integrated biomarker
      response (EIBR) were applied to indirectly/directly estimate the ecotoxicological
      risk of emerging organic contaminants in Taihu Lake. Nine out of sixteen target
      compounds were detected in most sampling points at comparable concentrations
      (1.58-206.95 ng/L). Simultaneously, changes in multi-biomarkers were measured in
      caged fish for 28 days. The 0HQ results preliminarily indicated that most water
      areas were at significant risk for adverse effects to aquatic organisms (HQ>10).
      The prioritisation was then ranked and 17alpha-ethinylestradiol,
      diethylstilbestrol and 17beta-estradiol were regarded as the greatest hazards.
      The EIBR, covering multi-biomarkers and their weighting, was applied to field
      study, and Zhushan Bay was suggested as the most stressful place, followed by
      Meiliang Bay. The HQ showed significant positive linear correlation with the EIBR
      (r=0.848, P<0.001), suggesting mutual consistency between the two approaches
      based on laboratory and field study in ecotoxicological risk assessment.

PMID- 24135492
TI  - A 700 year record of combustion-derived pollution in northern Spain: tools to
      identify the Holocene/Anthropocene transition in coastal environments.
AB  - There is an uneven geographical distribution of historic records of atmospheric
      pollutants from SW Europe and those that exist are very limited in temporal
      extent. Alternative data source is required to understand temporal trends in
      human impacts on atmospheric pollution. Polycyclic aromatic hydrocarbons (PAHs),
      heavy metal content and stable Pb isotopic ratios in a sediment core from a salt
      marsh in northern Spain were used to reconstruct the regional history of
      contaminant inputs over the last 700 years. Pre-1800s concentrations of Pb and
      PAHs represented baseline concentrations, i.e. pre-Industrial, conditions. During
      the initial stages of the Industrial Revolution, 1800s to 1860s, PAH
      concentrations increased by a factor of about two above baseline levels in the
      sediment column. By the 1930s, PAH levels reached ca. 10 times pre-Industrial
      levels and, along with Pb, reached a peak at ca. 1975 CE. Since then, sedimentary
      PAH and Pb concentrations decreased significantly. A combination of PAH isomer
      and Pb stable isotope ratios suggests that the contaminant sources are regional,
      likely derived partially from wood, but mainly coal used by the metallurgic
      industry in the Basque country since the 1800s and until the 1970s when leaded
      petrol saw increased use. This chronology of regional atmosphere-derived
      pollution expands current southwest Europe emission records and shows coastal
      salt marsh sediments to be useful in reconstructing the Anthropocene.

PMID- 24135493
TI  - Evaluation of the measurement properties of the Epworth sleepiness scale: a
      systematic review.
AB  - OBJECTIVE: To examine published evidence on the psychometric properties of the
      Epworth sleepiness scale (ESS) for describing the level of daytime sleepiness
      (DS) in adults. METHODS: Articles were located on MEDLINE and EMBASE.
      Psychometric properties were appraised using the COnsensus-based Standards for
      the selection of health status Measurement Instruments (COSMIN) checklist.
      RESULTS: We found thirty-five studies evaluating psychometric properties of the
      ESS in adults. Of these, 27 studies examined construct validity, 14 - known-group
      validity, 8 - internal consistency and 4 - test-retest reliability. Study quality
      ranged from excellent to poor the majority being fair. Internal consistency by
      Cronbach's alphas was good (0.73-0.86). There is little available evidence on
      test-retest reliability. Pooled correlations of the ESS with other constructs
      varied: from moderate (the maintenance of wakefulness test; rho = -0.43), to weak
      (the multiple sleep latency test; rho = -0.27, and sleep apnea-related variables;
      rho from 0.11 to 0.23). Although ESS scores varied significantly across groups of
      subjects with known differences in DS, not all differences were clinically
      important. CONCLUSION: There have been relatively few high quality studies on the
      ESS psychometric properties. The internal consistency of the ESS suggests that
      this instrument can be recommended for group but not individual-level
      comparisons. Correlations with other measures of DS were stronger than with sleep
      apnea-related or general health measures, but still lower than expected. Further
      studies are required in the areas of test-retest reliability of the ESS.

PMID- 24135494
TI  - Surgical correction of epiblepharon using an epicanthal weakening procedure with
      lash rotating sutures.
AB  - BACKGROUND: To describe a new surgical technique in patients with lower eyelid
      epiblepharon using an epicanthal weakening procedure with lash rotating sutures.
      METHODS: Charts of patients with epiblepharon who underwent surgical correction
      using an epicanthal weakening procedure with lash rotating sutures were reviewed
      retrospectively. The preoperative severity of corneal erosion was graded and
      compared with the postoperative keratopathy. Postoperative surgical outcomes,
      complications and subjective satisfaction were also evaluated. RESULTS: 202 eyes
      of 101 patients were evaluated in this study. The preoperative cilia-corneal
      touch was corrected and keratopathy was improved, especially towards the medial
      aspect of the lower lid. There were four eyes (2.0%) of recurrent cilia-corneal
      touch, but none required reoperation. Cosmetic outcomes were considered to be
      'very satisfied' in 95 patients, 'satisfied' in 6 patients, and no patients
      indicated 'neutral' or 'dissatisfied' results. CONCLUSIONS: In patients with
      epiblepharon with an epicanthal fold, surgical correction using an epicanthal
      weakening procedure with lash rotating sutures is a simple and effective method
      for correction, particularly when evaluating the medial portion of the lower
      eyelid. This method also produces a favourable cosmetic outcome with minimal scar
      formation.

PMID- 24135496
TI  - Tissue advanced glycation end product deposition after kidney transplantation.
AB  - BACKGROUND: Tissue advanced glycation end products (AGEs) accumulate in chronic
      kidney disease (CKD) and are a measure of cumulative metabolic stress.
      Measurement of tissue AGEs by skin autofluorescence (SAF) correlates well with
      cardiovascular outcomes in dialysis patients. SAF levels in transplant recipients
      relative to CKD and dialysis patients have not been previously studied, and the
      impact of transplantation on SAF levels in dialysis patients is unknown. METHODS:
      SAF was measured using an AGE reader in 66 patients who had received a kidney
      transplant. Values were compared to those obtained in 1,707 patients with CKD
      stage 3 and in 115 patients on dialysis. RESULTS: Mean SAF in transplant
      recipients [2.81 +/- 0.64 arbitrary units (AU)] was significantly lower than in
      patients on haemodialysis (3.73 +/- 0.88 AU) and peritoneal dialysis (3.57 +/-
      0.75 AU; p < 0.001), but was no different from CKD stage 3 (2.79 +/- 0.66 AU; p =
      0.42). In the transplant group, SAF correlated most strongly with age (r =
      0.316). There was no correlation between SAF and estimated glomerular filtration
      rate or renal replacement therapy vintage. A small cohort of patients with SAF
      recorded on dialysis and following transplantation showed a drop in SAF over a
      mean time of 16 months after transplantation. DISCUSSION: Tissue AGE values in
      kidney transplant recipients are significantly lower than in patients receiving
      dialysis and similar to those in patients with CKD stage 3. Our data suggest that
      transplantation may be associated with a reduction in tissue AGEs, and this might
      be an important component of the observed reduction in cardiovascular risk in
      transplant recipients compared to patients on dialysis.

PMID- 24135495
TI  - Mitophagy in hematopoietic stem cells: the case for exploration.
AB  - Hematopoietic stem cells (HSCs) are inherently quiescent and self-renewing, yet
      can differentiate and commit to multiple blood cell types. Intracellular
      mitochondrial content is dynamic, and there is an increase in mitochondrial
      content during differentiation and lineage commitment in HSCs. HSCs reside in a
      hypoxic niche within the bone marrow and rely heavily on glycolysis, while
      differentiated and committed progenitors rely on oxidative phosphorylation.
      Increased oxidative phosphorylation during differentiation and commitment is not
      only due to increased mitochondrial content but also due to changes in
      mitochondrial cytosolic distribution and efficiency. These changes in the
      intracellular mitochondrial landscape contribute signals toward regulating
      differentiation and commitment. Thus, a functional relationship exists between
      the mitochondria in HSCs and the state of the HSCs (i.e., stemness vs.
      differentiated). This review focuses on how autophagy-mediated mitochondrial
      clearance (i.e., mitophagy) may affect HSC mitochondrial content, thereby
      influencing the fate of HSCs and maintenance of hematopoietic homeostasis. 

PMID- 24135497
TI  - Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice:
      implications for the clinical management of LQT3 patients.
AB  - BACKGROUND: The efficacy of beta-blockers for treatment of patients with long QT
      syndrome type 3 (LQT3) has been repeatedly questioned, and it has been suggested
      that they might be detrimental for this genetic subgroup of patients with long QT
      syndrome (LQTS). The disquieting consequence has been that cardiologists
      confronted with LQT3 patients often do not even attempt pharmacologic therapy and
      implant cardioverter-defibrillators as first-choice treatment. However, the most
      recent clinical data indicate high efficacy of beta-blocker therapy in LQT3
      patients. OBJECTIVE: The purpose of this study was to test the antiarrhythmic
      efficacy of beta-blockers in an established experimental model for LQT3. METHODS:
      After phenotypic validation of 65 ?KPQ-SCN5A knock-in transgenic (TG) mice
      compared to 32 wild-type (WT) mice, we tested the effect of the arrhythmogenic
      cholinergic muscarinic agonist carbachol in 19 WT and 39 TG anesthetized mice,
      with and without pretreatment with propranolol given intraperitoneally. RESULTS:
      At the same heart rates, TG mice had a markedly longer QT interval than WT mice.
      Whereas carbachol had minor arrhythmic effects in the WT mice, it produced
      ventricular tachycardia (VT) and ventricular fibrillation (VF) in 55% of 20 TG
      mice. By contrast, in none of 19 TG mice pretreated with propranolol did VT/VF
      occur after carbachol injection. CONCLUSION: These experimental data indicate
      that, contrary to previous reports, beta-blockade effectively prevents VT/VF in a
      validated LQT3 model. Together with the most recent clinical data, these findings
      indicate that there is no reason for not initiating protective therapy with beta
      blockers in LQT3 patients.

PMID- 24135498
TI  - Transthoracic epicardial ablation of mitral isthmus for treatment of recurrent
      perimitral flutter.
AB  - BACKGROUND: Perimitral flutter (PMF) is a common form of left atrial tachycardia
      after atrial fibrillation (AF) ablation. The mitral isthmus (MI) is the standard
      ablation target. However, in some cases bidirectional block cannot be achieved.
      OBJECTIVE: The purpose of this study was to describe the first experience using a
      transthoracic epicardial (TTE) approach to treat recurrent PMF after prior
      unsuccessful ablation. METHODS: This is a case series of four patients with
      recurrence of highly symptomatic drug-refractory PMF (all male, median age 55
      years, 3/4 hypertensive, 2/4 persistent AF, median AF period 24 months). Three
      patients presented with PMF-related tachymyocardiopathy. TTE ablation of MI was
      performed after a median of two prior endocardial MI and coronary sinus ablation
      attempts, using an open-tip 3.5-mm irrigated catheter (40 W, 45oC). Persistent
      bidirectional block was assessed by activation mapping and differential pacing
      and was achieved in all patients. RESULTS: No PMF recurrence was observed after
      median follow-up of 18 months (range 15-22 months; two patients without
      antiarrhythmic drugs and two with previously ineffective amiodarone). Left
      ventricular function normalized in all three patients with tachycardiomyopathy.
      There were no complications related to TTE approach. CONCLUSION: The present
      study is the first to report the feasibility of a TTE approach for highly
      symptomatic PMF refractory to endocardial and coronary sinus MI ablation.

PMID- 24135499
TI  - Axitinib, a selective inhibitor of vascular endothelial growth factor receptor,
      exerts an anticancer effect in melanoma through promoting antitumor immunity.
AB  - In this study, we investigated the antitumor activity of axitinib, a selective
      inhibitor of vascular endothelial growth factor receptor tyrosine kinases,
      against melanoma cells. Axitinib dose-dependently inhibited the proliferation and
      induced the apoptosis of B16F1 cells in vitro. In a mouse model of melanoma
      xenograft, axitinib significantly suppressed tumor growth and induced apoptosis
      of cells in tumor tissues at a dose of 25 mg/kg. In addition, axitinib suppressed
      the lung metastasis of melanoma cells and prolonged the life span of tumor
      bearing mice. Axitinib also enhanced the proportion of CD8+ T cells and reduced
      the proportion of myeloid-derived suppressor cells in CD45.2+ cells, whereas the
      proportions of CD4+ T cells and Treg cells were not affected. The mRNA
      expressions of inducible nitric oxide synthases-2 and arginase-1, which were
      associated with the function of myeloid-derived suppressor cells in tumor
      tissues, were inhibited by axitinib. Moreover, axitinib suppressed the
      expressions of proinflammatory cytokines such as IL-6, TNF-alpha, and IFN-gamma.
      Altogether, our results showed the unique antitumor mechanism of axitinib and
      provided useful information for its clinical application.

PMID- 24135500
TI  - Vitamin D in endometriosis: a causative or confounding factor?
AB  - OBJECTIVE: The aim of this paper is to review the evidence from studies that
      evaluated the relationship between vitamin D and endometriosis. DESIGN:
      Comprehensive review. MATERIALS AND METHODS: Systematic literature search in
      Medline for relevant publications from 1946 until June 2013. RESULTS:
      Endometriosis risk may be influenced by dietary vitamin D intake and plasma
      hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing
      enzymes, 24-hydroxylase and 1-alpha hydroxylase, are found in the normal cycling
      endometrium and also in the eutopic and ectopic endometrium of women with
      endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions
      through regulation of specific genes and via immunomodulation. The endometrium in
      endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If
      vitamin D and its metabolites are implicated in endometriosis-associated
      infertility, it is likely through interference with HOXA10 gene expression. The
      Gc2 phenotype of vitamin D binding protein is prevalent in women with
      endometriosis and may be implicated in its pathogenesis. In a mouse model,
      Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic
      lesions and recurrence. CONCLUSION: A biological plausibility for a role of
      vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis
      and treatment of endometriosis is suggested in this article, but is difficult to
      illustrate due to sparse evidence from human studies limited primarily to case
      control studies. A significant knowledge gap precludes the establishment of a
      clear cause-effect relationship. The intriguing leads presented herein need to be
      investigated further with placebo-controlled supplementation trials.

PMID- 24135501
TI  - Intestinal gluconeogenesis is crucial to maintain a physiological fasting
      glycemia in the absence of hepatic glucose production in mice.
AB  - OBJECTIVE: Similar to the liver and kidneys, the intestine has been strongly
      suggested to be a gluconeogenic organ. However, the precise contribution of the
      intestine to endogenous glucose production (EGP) remains to be determined. To
      define the quantitative role of intestinal gluconeogenesis during long-term
      fasting, we compared changes in blood glucose during prolonged fasting in mice
      with a liver-deletion of the glucose-6 phosphatase catalytic (G6PC) subunit (LKO)
      and in mice with a combined deletion of G6PC in both the liver and the intestine
      (ILKO). MATERIALS/METHODS: The LKO and ILKO mice were studied after 6h and 40 h
      of fasting by measuring metabolic and hormonal plasmatic parameters, as well as
      the expression of gluconeogenic enzymes in the liver, kidneys and intestine.
      RESULTS: After a transient hypoglycemic episode (approximately 60 mg/dL) because
      of their incapacity to mobilize liver glycogen, the LKO mice progressively re
      increased their plasma glucose to reach a glycemia comparable to that of wild
      type mice (90 mg/dL) from 30 h of fasting. This increase was associated with a
      rapid induction of renal and intestinal gluconeogenic gene expression, driven by
      glucagon, glucocorticoids and acidosis. The ILKO mice exhibited a similar
      induction of renal gluconeogenesis. However, these mice failed to re-increase
      their glycemia and maintained a plasma glucose level of only 60 mg/dL throughout
      the 48 h-fasting period. CONCLUSIONS: These data indicate that intestinal glucose
      production is essential to maintain glucose homeostasis in the absence of hepatic
      glucose production during fasting. These data provide a definitive quantitative
      estimate of the capacity of intestinal gluconeogenesis to sustain EGP during long
      term fasting.

PMID- 24135502
TI  - Obesity accelerates ovarian follicle development and follicle loss in rats.
AB  - OBJECTIVE: Studies have shown that excess body fat negatively affects
      reproductive functions in females. However, whether obesity affects the ovarian
      follicle development and ovarian lifespan and the underlying mechanism has not
      been well elucidated. The aim of the present study was to investigate the
      association between obesity and ovarian follicle development. METHODS: Adult
      female Sprague-Dawley rats (n = 36) were randomly divided into three groups: the
      normal control (NC) group, the caloric restriction (CR) group (fed 70% food of
      the NC group) and the high-fat diet (HF) group. They were maintained on these
      regimens for 18 weeks. RESULTS: The body weight, ovary weight and visceral fat in
      the HF group were significantly higher than those in the NC group and the CR
      group at the end of treatment. Histological analysis showed that the HF rats had
      significantly less number and percentage of primordial follicles, but greater
      number and percentage of developing and atretic follicles than the NC rats and CR
      rats. Western blot analysis demonstrated that the level of mTORC1 and p-S6K1
      proteins significantly increased in the ovaries of HF rats, whereas that of
      SIRT1, SIRT6, FOXO3a and NRF-1 decreased compared to the NC rats. In contrast,
      the expression of mTORC1 and p-S6K1 dramatically declined, while that of SIRT1,
      SIRT6, FOXO3a and NRF1 increased in the ovaries of CR rats. CONCLUSIONS: Our
      study suggests that the HF diet induced obesity may accelerate the ovarian
      follicle development and rate of follicle loss through activating mTOR and
      suppressing SIRT1 signaling, thus leading to POF, and that CR may inhibit the
      activation of primordial follicles, follicular development and loss, thus
      extending the ovarian lifespan through suppressing mTOR and activating SIRT1
      signaling.

PMID- 24135503
TI  - Woman with right lower quadrant mass and abdominal pain.

PMID- 24135504
TI  - Magnet balls stuck to the frenulum of the lip.
AB  - BACKGROUND: Accidents associated with magnets as foreign bodies pose a serious
      threat to the health of children and adolescents. Prompt management and removal
      of the magnet is important to avoid life-threatening complications. OBJECTIVE:
      Our aim was to highlight an unusual health hazard associated with magnets in
      children. CASE REPORT: We report on a unique case of an adolescent girl who
      presented with two magnet balls stuck to the frenulum of her upper lip, resulting
      in intense pain and discomfort. The magnets were removed painlessly by induced
      magnetism through metallic mosquito forceps. CONCLUSIONS: As children experiment
      with toys and products containing detachable magnetic balls, more cases will
      likely present to emergency departments. Increased awareness and preventive
      measures should be undertaken to reduce the morbidity and mortality associated
      with magnets.

PMID- 24135505
TI  - New heights in ultrasound: first report of spinal ultrasound from the
      international space station.
AB  - BACKGROUND: Changes in the lumbar and sacral spine occur with exposure to
      microgravity in astronauts; monitoring these alterations without radiographic
      capabilities on the International Space Station (ISS) requires novel diagnostic
      solutions to be developed. STUDY OBJECTIVES: We evaluated the ability of point-of
      care ultrasound, performed by nonexpert-operator astronauts, to provide accurate
      anatomic information about the spine in long-duration crewmembers in space.
      METHODS: Astronauts received brief ultrasound instruction on the ground and
      performed in-flight cervical and lumbosacral ultrasound examinations using just
      in-time training and remote expert tele-ultrasound guidance. Ultrasound
      examinations on the ISS used a portable ultrasound device with real-time
      communication/guidance with ground experts in Mission Control. RESULTS: The
      crewmembers were able to obtain diagnostic-quality examinations of the cervical
      and lumbar spine that would provide essential information about acute or chronic
      changes to the spine. CONCLUSIONS: Spinal ultrasound provides essential anatomic
      information in the cervical and lumbosacral spine; this technique may be
      extensible to point-of-care situations in emergency departments or resource
      challenged areas without direct access to additional radiologic capabilities.

PMID- 24135506
TI  - Bipolar disorder and stigma: a systematic review of the literature.
AB  - AIM: The degree to which bipolar disorder is stigmatised by the public and the
      extent of internalised stigma for people with this disorder, their families, and
      carers has been a relatively neglected area of research. This review aimed to
      determine what is currently known about stigma and bipolar disorder. METHOD: A
      systematic search of the literature was conducted to identify publications which
      investigated public attitudes and/or beliefs about bipolar disorder or explored
      internalised stigma in bipolar disorder. The electronic databases PsychINFO,
      Medline, Embase, and Web of Science were searched for articles published between
      1992 and 2012. RESULTS: Twenty five articles met the reviews inclusion criteria.
      There are inconsistent findings regarding public stigma, although there is some
      evidence that bipolar disorder is viewed more positively than schizophrenia and
      less positively than depression. There is a moderate to high degree of
      internalised stigma in bipolar disorder, although the literature raises questions
      regarding its ubiquity in this population. LIMITATIONS: Limiting the search by
      year of publication and excluding studies where stigma was not the main focus
      could mean stigma has wider implications than were identified. CONCLUSIONS: This
      review is the first systematic synthesis of research relating to stigma and
      bipolar disorder. In comparison to research on other mental health problems,
      there is a dearth of literature exploring stigma in bipolar disorder. The
      literature is largely inconclusive. Future research is needed to replicate
      tentative findings and address methodological limitations before the field can
      move on to the development of anti-stigma interventions.

PMID- 24135507
TI  - Predictors of suicidal ideation among depressed Veterans and the interpersonal
      theory of suicide.
AB  - BACKGROUND: We assessed whether key constructs of the interpersonal theory of
      suicide were associated with suicidal ideation in depressed US Veterans. METHODS:
      443 patients of the Veterans Health Administration diagnosed with a depressive
      disorder completed the Beck Depression Inventory, Interpersonal Support
      Evaluation List, and Beck Hopelessness Scale, from which we derived measures of
      burdensomeness, belongingness, and hopelessness consistent with the interpersonal
      theory of suicide. Measures of active and passive suicidal ideation were
      constructed from the Beck Suicide Scale and Beck Depression Inventory obtained at
      baseline and 3-months follow-up. Multivariable logistic regression was used to
      identify predictors of passive and active suicidal ideation while adjusting for
      demographic characteristics and somatic-affective symptoms of depression (e.g.,
      anhedonia, insomnia). RESULTS: Burdensomeness and hopelessness were significantly
      associated with passive suicidal ideation at baseline and 3 months follow-up, but
      belongingness and the interaction between belongingness and burdensomeness were
      not significant predictors as proposed by the interpersonal theory of suicide.
      Somatic-affective depressive symptoms, but not any of the main effects predicted
      by the interpersonal theory of suicide or their interactions, were associated
      with active suicidal ideation at baseline. No factors were consistently
      associated with active suicidal ideation at 3 months follow-up. LIMITATIONS: The
      measure of burdensomeness used in this study only partially represents the
      construct described by the interpersonal theory of suicide. CONCLUSION: We found
      little support for the predictions of the interpersonal theory of suicide.
      Hopelessness appears to be an important determinant of passive suicidal ideation,
      while somatic-affective depression symptoms may be a key contributor to active
      suicidal ideation.

PMID- 24135508
TI  - Post-traumatic stress disorder in DSM-5: estimates of prevalence and criteria
      comparison versus DSM-IV-TR in a non-clinical sample of earthquake survivors.
AB  - BACKGROUND: The latest edition of DSM (DSM-5) introduced important revisions to
      PTSD symptomatological criteria, such as a four-factor model and the inclusion of
      new symptoms. To date, only a few studies have investigated the impact that the
      proposed DSM-5 criteria will have on prevalence rates of PTSD. METHODS: An
      overall sample of 512 adolescents who survived the L'Aquila 2009 earthquake and
      were previously investigated for the presence of full and partial PTSD, using DSM
      IV-TR criteria, were reassessed according to DSM-5 criteria. All subjects
      completed the Trauma and Loss Spectrum-Self Report (TALS-SR). RESULTS: A DSM-5
      PTSD diagnosis emerged in 39.8% of subjects, with a significant difference
      between the two sexes (p<0.001), and an overall 87.1% consistency with DSM-IV-TR.
      Most of the inconsistent diagnoses that fulfilled DSM-IV-TR criteria but not DSM
      5 criteria can be attributed to the subjects not fulfilling the new criterion C
      (active avoidance). Each DSM-5 symptom was more highly correlated with its
      corresponding symptom cluster than with other symptom clusters, but two of the
      new symptoms showed moderate to weak item-cluster correlations. Among DSM-5 PTSD
      cases: 7 (3.4%) endorsed symptom D3; 151 (74%) D4; 28 (13.7%) both D3 and D4; 75
      (36.8%) E2. LIMITATIONS: The use of a self-report instrument; no information on
      comorbidity; homogeneity of study sample; lack of assessment on functional
      impairment; the rates of DSM-IV-TR qualified PTSD in the sample was only 37.5%.
      CONCLUSIONS: This study provides an inside look at the empirical performance of
      the DSM-5 PTSD criteria in a population exposed to a natural disaster, which
      suggests the need for replication in larger epidemiological samples.

PMID- 24135509
TI  - Effects of extended-release quetiapine fumarate on long-term functioning and
      sleep quality in patients with Generalized Anxiety Disorder (GAD): data from a
      randomized-withdrawal, placebo-controlled maintenance study.
AB  - BACKGROUND: This analysis evaluated effects of quetiapine XR maintenance
      treatment on functioning and sleep in patients with GAD. METHODS: Analysis of
      patient-reported data from a randomized-withdrawal, double-blind, placebo
      controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in
      (4-8 weeks) and a 12-18-week stabilization phase (quetiapine XR 50, 150, or 300
      mg/day), eligible patients were randomized to continue on quetiapine XR or
      receive placebo for up to 52 weeks. Primary variable was time to an anxiety
      event. Secondary variables included the Sheehan Disability Scale (SDS) and
      Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 432 patients were
      randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event
      was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12,
      0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS
      total scores (LSM change: -0.19 vs. 1.01; p=0.017) and non-work-related SDS
      domain score 'family life/home responsibilities' (-0.13 vs. 0.32; p=0.011), but
      not 'social life' (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than
      placebo at maintaining the work-related SDS domain score 'days lost' (-0.05 vs.
      0.11; p=0.027), but not 'work/school' (-0.10 vs. 0.29; p=0.051) or 'days
      underproductive' (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from
      randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).
      LIMITATIONS: Lack of active-comparator arm, exclusion of patients with comorbid
      depression. CONCLUSIONS: In patients with GAD, long-term treatment with
      quetiapine XR (50-300 mg/day) monotherapy was effective at maintaining
      improvements in functioning and sleep quality.

PMID- 24135510
TI  - Bright spots: Q fever prosthetic valve endocarditis.

PMID- 24135511
TI  - Systematic PCR detection in culture-negative osteoarticular infections.
AB  - BACKGROUND: Identification of microorganisms is crucial for the successful
      treatment of osteoarticular infections. Molecular methods are more sensitive than
      culture-dependent methods but may suffer from lack of specificity. METHODS: We
      studied a large series of 3840 bone and joint culture-negative samples collected
      from 2308 patients hospitalized in Marseille University Hospitals from November
      2007 to October 2009. The samples were systematically cultured for 15 days, and
      conventional broad-range polymerase chain reaction (PCR) (16S rDNA and 18S rDNA)
      as well as real-time PCR assays targeting human Bglobin, Staphylococcus aureus,
      and Kingella kingae were realized on one culture-negative specimen. RESULTS:
      Specimens from 741 patients (32.1%) tested positive by culture, including 38 in
      which bacteria grew only after 6 days of incubation. PCR was positive in 141 (9%)
      culture-negative specimens. Microorganisms identified by PCR were classified into
      2 groups: fastidious bacteria (n = 35), mostly anaerobes in adult patients, and
      K. kingae in children; and nonfastidious bacteria (n = 106), mostly S. aureus
      (32.7%). A discrepancy between a positive PCR result for S. aureus and a negative
      culture were explained by previous antibiotherapy in 31.4% of cases. Our study
      highlights the usefulness of systematic 16S rDNA gene PCR for the diagnosis of
      bone and joint infections in culture-negative patients, thus enabling the
      administration of specific antibiotic treatments. CONCLUSIONS: We recommend the
      use of conventional broad-range PCR for culture-negative bone and joint
      specimens, as well as S. aureus-specific PCR for adults and K. kingae-specific
      PCR for children. 18S rDNA PCR should be reserved only for specific cases.

PMID- 24135512
TI  - A looming danger: pheochromocytoma.

PMID- 24135513
TI  - A randomized controlled trial of a community-based behavioral counseling program.
AB  - BACKGROUND: The US Preventive Services Task Force (USPSTF) recommends that
      clinicians refer obese adults for intensive, multicomponent behavioral
      counseling, yet most obese Americans choose a self-help approach to lose weight.
      The current study examined weight loss between a community-based, intensive
      behavioral counseling program (Weight Watchers program) and a self-help
      condition. METHODS: A total of 292 participants were randomized to either a
      Weight Watchers condition (WW) (n = 147) or a self-help condition (n = 145).
      Participants in the WW condition were provided with 3 ways to access the
      treatment: weekly meetings; WW mobile application; and WW online tools. Weights
      were measured at baseline and at 3 and 6 months. Additionally, self-report use of
      access modes was collected at 3 and 6 months. RESULTS: Participants in the WW
      condition significantly decreased their body mass index at 6 months (F = 36.7, P
      <.001) and were 8.0 and 8.8 times more likely to achieve a 5% and 10% reduction
      in weight, respectively, compared with those in the self-help condition. In a
      secondary analysis, high usage of all 3 access modes resulted in the greatest
      weight loss (P <.001). CONCLUSION: Use of the WW program yielded significantly
      greater weight loss than a self-help approach, suggesting it is a viable
      community-based provider of weight loss treatment, as recommended by the USPSTF.
      Further, high usage of 3 access modes was associated with greater weight loss
      results.

PMID- 24135514
TI  - Dietary fiber intake and cardiometabolic risks among US adults, NHANES 1999-2010.
AB  - BACKGROUND: Dietary fiber may decrease the risk of cardiovascular disease and
      associated risk factors. We examined trends in dietary fiber intake among diverse
      US adults between 1999 and 2010, and investigated associations between dietary
      fiber intake and cardiometabolic risks including metabolic syndrome,
      cardiovascular inflammation, and obesity. METHODS: Our cross-sectional analysis
      included 23,168 men and nonpregnant women aged 20+ years from the 1999-2010
      National Health and Nutrition Examination Survey. We used weighted multivariable
      logistic regression models to estimate predicted marginal risk ratios and 95%
      confidence intervals for the risks of having the metabolic syndrome,
      inflammation, and obesity associated with quintiles of dietary fiber intake.
      RESULTS: Consistently, dietary fiber intake remained below recommended adequate
      intake levels for total fiber defined by the Institute of Medicine. Mean dietary
      fiber intake averaged 15.7-17.0 g. Mexican Americans (18.8 g) consumed more fiber
      than non-Hispanic whites (16.3 g) and non-Hispanic blacks (13.1 g). Comparing the
      highest with the lowest quintiles of dietary fiber intake, adjusted predicted
      marginal risk ratios (95% confidence interval) for the metabolic syndrome,
      inflammation, and obesity were 0.78 (0.69-0.88), 0.66 (0.61-0.72), and 0.77 (0.71
      0.84), respectively. Dietary fiber was associated with lower levels of
      inflammation within each racial and ethnic group, although statistically
      significant associations between dietary fiber and either obesity or metabolic
      syndrome were seen only among whites. CONCLUSIONS: Low dietary fiber intake from
      1999-2010 in the US, and associations between higher dietary fiber and a lower
      prevalence of cardiometabolic risks suggest the need to develop new strategies
      and policies to increase dietary fiber intake.

PMID- 24135515
TI  - The risk of cancer in patients with benign anal lesions: a nationwide population
      based study.
AB  - OBJECTIVE: To evaluate the risk of cancer among patients diagnosed with
      hemorrhoids and benign anal inflammatory lesions. METHODS: A population-based,
      retrospective cohort study was conducted that included patients diagnosed with
      hemorrhoids or benign inflammatory anal lesions (eg, anal fissure, fistula, and
      perianal abscesses) that were registered in the National Health Insurance
      Research Database in Taiwan between January 1, 2000 and December 31, 2010.
      Standardized incidence ratios (SIRs) were calculated to compare the cancer
      incidence of these patients to the general population. RESULTS: During a median
      observation period of 6.23 years, 3080 cancers developed among 70,513 hemorrhoid
      patients, with a follow-up period of 438,425.6 person-years, entailing the SIR of
      1.52 (95% confidence interval [CI], 1.47-1.58). Increased cancer risk (SIR 1.16;
      95% CI, 1.11-1.21) was still noted even after excluding the first year of
      observation. Significant long-term risk for colorectal cancer (SIR 1.50; 95% CI,
      1.35-1.66) and prostate cancer (SIR 1.40; 95% CI, 1.17-1.66) was observed after
      corrections were made for multiple comparisons. In contrast, there was no
      remarkable increase in cancer risk for patients with inflammatory anal lesions
      when cancers detected within the first year of diagnosis were excluded.
      CONCLUSION: The presence of hemorrhoids is associated significantly with a long
      term risk of developing colorectal cancer or prostate cancer. In contrast, benign
      inflammatory anal lesions do not appear to increase the risk of malignancy.

PMID- 24135516
TI  - Abnormalities in cytokine secretion from mesenchymal stem cells in psoriatic skin
      lesions.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory and proliferative skin disease
      associated with immune abnormalities. In our preliminary studies, it was found
      that bone marrow mesenchymal stem cells (BMSCs) were abnormal in patients with
      psoriasis. Mesenchymal stem cells (MSCs) are not only present in the bone marrow,
      but can also be separated from the skin.We reasoned that an investigation into
      the biological characteristics of MSCs in psoriatic skin lesions could more
      realistically reflect the actual conditions for the pathogenesis of psoriasis.
      OBJECTIVE: To reveal whether MSCs in psoriatic skin lesions are abnormal.
      METHODS: We obtained MSCs from psoriatic skin lesions and healthy human skin and
      identified these cells using flow cytometry and a cell differentiation assay;
      cytokine concentrations in the culture supernatants were measured with the ELISA
      assay. We compared cytokine concentrations in culture supernatants of MSCs
      derived from psoriatic skin lesions as well as those from healthy human skin.
      RESULTS: Compared with healthy control skintissue, in psoriatic skin lesions, MSC
      secretion of EGF, SCF, and IL-11 increased; secretion of bFGF, IL-3, IL-6, IL-8,
      and HGF decreased (p<0.05); and secretion of VEGF, M-CSF, G-CSF, GM-CSF, LIF, IL
      1, IL-7, IL-10, and TNF-alpha showed no significant difference (p>0.05). Surface
      markers and the differentiation capacity of cells from the two sources were
      similar. CONCLUSION: This study demonstrated that MSCs derived from psoriatic
      skin lesions had abnormalities, which may be one of the pathogenic mechanisms of
      psoriasis.

PMID- 24135517
TI  - Research apotheosis.

PMID- 24135518
TI  - Management of needle breakage using intraoperative navigation following inferior
      alveolar nerve block.
AB  - This report describes a peculiar case of needle breakage during inferior alveolar
      nerve block to perform third molar extraction that was removed with the aid of a
      BrainLAB VectorVision neuronavigation system. This report adds to the currently
      limited scientific literature on the image-guided removal of foreign bodies from
      the oral cavity. 

PMID- 24135519
TI  - Recurrence of nasopharyngeal carcinoma in the parotid region after definitive
      intensity-modulated radiotherapy.
AB  - PURPOSE: To discuss the clinical characteristics and management of periparotid
      recurrence of nasopharyngeal carcinoma after definitive intensity-modulated
      radiotherapy. PATIENTS AND METHODS: The authors retrospectively reviewed the
      charts of 716 patients with nasopharyngeal carcinoma who underwent intensity
      modulated radiotherapy at their center from January 2005 through December 2010.
      Disease recurred in a spared parotid gland in 10 patients (1.4%). After
      periparotid recurrence, 4 patients received surgery alone, 1 patient received
      radiotherapy alone, 2 patients received chemotherapy alone, 2 patients received
      surgery plus chemotherapy, and 1 patient received surgery plus radiotherapy.
      RESULTS: After a median follow-up of 42.6 months (19.8 to 86.0 months), 4
      patients died of tumor progression. The median survival time after periparotid
      recurrence was 25.1 months (5.0 to 74.5 months). CONCLUSIONS: Periparotid
      recurrence is an uncommon pattern of failure after definitive intensity-modulated
      radiotherapy for nasopharyngeal carcinoma, and there were some long-term
      survivors in this patient population after salvage treatment.

PMID- 24135520
TI  - Povidone-iodine and hydrogen peroxide mixture soaked gauze pack: a novel
      hemostatic technique.
AB  - Persistent oozing of blood is a common occurrence in maxillofacial surgery, and
      occasionally it hampers visibility and delays or even prevents continuation of
      the procedure. This report describes a novel method of controlling blood ooze
      using swabs soaked with povidone-iodine and hydrogen peroxide (PI-HP pack) that
      is particularly useful in relatively inaccessible areas of the maxillofacial
      region. 

PMID- 24135521
TI  - Trabecular bone microarchitecture in the median palate and maxillary premolar
      alveolar sites of edentulous elderly cadavers.
AB  - PURPOSE: The median palate has been proposed as an alternative site for implant
      placement supporting maxillary overdentures. The aim of our research was to
      compare the histologic bone microarchitecture of the median palatal and the
      maxillary premolar alveolar ridge in edentulous elderly human cadavers. MATERIALS
      AND METHODS: The bone quality and quantity were analyzed at two regions of
      analysis (ROA) in 16 maxilla of human cadavers: the median palate (ROA I) and
      edentulous maxillary alveolar premolar ridge (ROA II). Histomorphometry of the
      scanned images was performed using image analysis software (National Institutes
      of Health ImageJ). The bone volume/tissue volume ratio, trabecular thickness,
      trabecular separation, and trabecular number were evaluated for the two regions.
      RESULTS: The bone volume fraction of the median-palatal region (ROA I) was
      greater than at the respective premolar sites (ROA II) in 10 of 15 samples
      (66.6%), with mean values ranging from 19.3-61.3%. However, the results were not
      statistically significant (P = .151). Similarly, the trabecular number of ROA II
      showed greater values than that for ROA II (mean TbN for ROA I, 1.03 mm(-1) and
      for ROA II, 0.96 mm(-1)). However, these differences were not statistically
      significant (P = .454). CONCLUSIONS: These results have indicated that the
      anterior median palate is structurally similar to the corresponding maxillary
      premolar region in elderly edentulous persons. Therefore, it can be used as an
      implant site to anchor a maxillary overdenture in patients with atrophic
      maxillary ridges.

PMID- 24135522
TI  - Assessment of the quality of life of patients with oral cancer after pectoralis
      major myocutaneous flap reconstruction with a focus on speech.
AB  - PURPOSE: The aim of the present study was to evaluate the quality of life (QoL)
      of patients with oral cancer who had undergone resection of the tongue and floor
      of the mouth and reconstruction with the pectoralis major flap. MATERIALS AND
      METHODS: The present study assessed 21 patients who had undergone pectoralis
      major flap reconstruction using the University of Washington QoL, version 4,
      questionnaire. A nonparametric Mann-Whitney U test was used to analyze the data.
      RESULTS: Of the 12 disease-specific domains, the best 3 scores from the patients
      were for pain, saliva, and anxiety, and the worst 3 scores were for taste,
      chewing, and swallowing. The mean UW-QoL composite score was 73.4. Swallowing was
      considered to be the most important issue within the previous 7 days, followed by
      chewing and speech. Those patients who had undergone wider excision had poorer
      speech. CONCLUSIONS: A significant effect was found on the QoL of patients with
      oral cancer who had undergone resection of the tongue and floor of the mouth with
      pectoralis major flap reconstruction.

PMID- 24135523
TI  - Pectoralis major myocutaneous flap--still a workhorse for maxillofacial
      reconstruction in developing countries.
AB  - PURPOSE: To retrospectively evaluate the utility of the pectoralis major
      myocutaneous (PMMC) flap for head, face, and neck (HFN) reconstruction in the
      Indian population. MATERIALS AND METHODS: The hospital records of 496 patients in
      whom the PMMC flap was used (saving the deltopectoral flap) for reconstruction of
      HFN defects from January 1991 to December 2010 were reviewed retrospectively. All
      the patients were followed up for a minimum period of 6 months, and the utility
      of the PMMC flap was evaluated for HFN reconstruction. RESULTS: Of the 496
      patients, complications developed in 84 patients. The complications included
      complete flap failure in 12, partial skin paddle loss in 24, wound infection in
      12, peripheral wound dehiscence in 16, plate exposure in 12, and donor site
      morbidity such as infection and a decrease in function in 8. CONCLUSIONS: The
      PMMC flap or its modification was used in 496 cases of reconstruction after
      resection surgery for malignancy of the HFN region with minimal morbidity and 1
      death. This technique is a useful alternative in places with a high incidence of
      HFN malignancies and microsurgical free tissue transfer is not possible or as a
      salvage procedure in selected large, full-thickness, oral cavity lesions. In our
      19-year experience, the final functional and cosmetic results were satisfactory
      with this sturdy flap.

PMID- 24135524
TI  - Low-dose tissue plasminogen activator and standard-dose tissue plasminogen
      activator in acute ischemic stroke in Asian populations: a review.
AB  - BACKGROUND: The burden of stroke is becoming an important issue in Asian
      countries, where half of the world's population lives. In Western populations,
      standard-dose intravenous tissue plasminogen activator (tPA) at a dose of 0.9
      mg/kg administered up to 4.5 h following acute ischaemic stroke has been shown to
      improve clinical outcomes. However, the dosage of tPA in Asian populations
      varies, partly influenced by treatment costs in developing countries and the
      perceived racial differences in treatment response. Furthermore, no randomized
      controlled trial of intravenous tPA thrombolysis has been carried out in Asia
      with the exceptions of observational and multicentre registries in Japan. SUMMARY
      OF THE REVIEW: This review aims to examine the current use of low-dose tPA in
      Asian populations with particular emphasis on its clinical benefits.
      Historically, the findings of 2-chain tPA (duteplase) trials in the early 1990s
      were the basis of low-dose tPA in Japan, and standard-dose tPA was chosen taking
      into account a pilot dose escalation study. Most of the trials incorporating low
      dose tPA suggested that low-dose tPA has clinical efficacy comparable with the
      standard dose and that it is associated with a lower incidence of symptomatic
      haemorrhage. It follows that consensus regarding the dosage of tPA is wanting.
      CONCLUSIONS: Standard-dose tPA would be a reasonable choice in Asian populations
      until the results are available from randomized controlled studies comparing low
      dose with standard-dose tPA.

PMID- 24135525
TI  - Progression of brain lesions in relation to hyperperfusion from subacute to
      chronic stages after experimental subarachnoid hemorrhage: a multiparametric MRI
      study.
AB  - BACKGROUND: The pathogenesis of delayed cerebral injury after aneurysmal
      subarachnoid hemorrhage (SAH) is largely unresolved. In particular, the
      progression and interplay of tissue and perfusion changes, which can
      significantly affect the outcome, remain unclear. Only a few studies have
      assessed pathophysiological developments between subacute and chronic time points
      after SAH, which may be ideally studied with noninvasive methods in standardized
      animal models. Therefore, our objective was to characterize the pattern and
      correlation of brain perfusion and lesion status with serial multiparametric
      magnetic resonance imaging (MRI) from subacute to chronical after experimental
      SAH in rats. METHODS: SAH was induced by endovascular puncture of the
      intracranial bifurcation of the right internal carotid artery in adult male
      Wistar rats (n = 30). Diffusion-, T2-, perfusion- and contrast-enhanced T1
      weighted MRI were performed on a 4.7-tesla animal MR system to measure cytotoxic
      and vasogenic edema, hemodynamic parameters and blood-brain barrier permeability,
      respectively, at days 2 and 7 after SAH. The neurological status was repeatedly
      monitored with different behavioral tests between days -1 and 7 after SAH.
      Lesioned tissue - identified by edema-associated T2 prolongation - and unaffected
      tissue were outlined on multislice images and further characterized based on
      tissue and perfusion indices. Correlation analyses were performed to evaluate
      relationships between different MRI-based parameters and between MRI-based
      parameters and neurological scores. RESULTS: Similar to clinical SAH and previous
      studies in this experimental SAH model, mortality up to day 2 was high (43%). In
      surviving animals, neurological function was significantly impaired subacutely,
      and tissue damage (characterized by T2 prolongation and diffusion reduction) and
      blood-brain barrier leakage (characterized by contrast agent extravasation) were
      apparent in ipsilateral cortical and subcortical tissue as well as in
      contralateral cortical tissue. Notably, ipsilateral cortical areas revealed
      increased cerebral blood flow and volume. Animals that subsequently died between
      days 2 and 7 after SAH had markedly elevated ipsilateral perfusion levels at day
      2. After a week, neurological function had improved in surviving animals, and
      brain edema was partially resolved, while blood-brain barrier permeability and
      hyperperfusion persisted. The degree of brain damage correlated significantly
      with the level of perfusion elevation (r = 0.78 and 0.85 at days 2 and 7,
      respectively; p < 0.05). Furthermore, chronic (day 7 after SAH) blood-brain
      barrier permeability and vasogenic edema formation were associated with subacute
      (day 2 after SAH) hyperperfusion (r = 0.53 and 0.66, respectively; p < 0.05).
      CONCLUSION: Our imaging findings indicate that SAH-induced brain injury at later
      stages is associated with progressive changes in tissue perfusion and that
      chronic hyperperfusion may contribute or point to delayed cerebral damage.
      Furthermore, multiparametric MRI may significantly aid in diagnosing the brain's
      status after SAH.

PMID- 24135526
TI  - Clevidipine rapidly and safely reduces blood pressure in acute intracerebral
      hemorrhage: the ACCELERATE trial.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with
      mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate
      hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute
      Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment)
      is a pilot study representing the first evaluation of safety and efficacy of
      intravenous clevidipine for the rapid treatment of hypertension in ICH patients.
      METHODS: ICH patients with a systolic BP (SBP) >160 mm Hg who present within 6 h
      (n = 27) or 12 h (n = 10) of symptoms were prospectively enrolled, treated with
      open-label clevidipine until SBP <=160 mm Hg was achieved and then titrated to
      keep target SBP between 140-160 mm Hg. RESULTS: A total of 35 patients with
      baseline median Glasgow Coma Scale score of 12, median NIH Stroke Scale score of
      14, mean SBP of 186 mm Hg and a mean time from onset of symptoms of 5.5 h
      received clevidipine. Median time to achieve SBP target range was 5.5 min. All
      patients achieved target SBP within 30 min; 96.9% achieved target SBP with
      clevidipine monotherapy. CT scans showed minimal hematoma volume change for the
      overall population (median change 0.01 ml, -2.9%). Mild/moderate hypotension was
      reported in 3 patients and resolved with dose reduction or drug discontinuation.
      CONCLUSION: Clevidipine monotherapy was effective and safe for rapid BP reduction
      in this cohort of critically ill ICH patients. Overall, patients showed minimal
      hematoma expansion with BP reduction, suggesting that rapid BP control with
      clevidipine may have a beneficial impact on hematoma expansion and warrants
      further investigation.

PMID- 24135528
TI  - Pairing neuropathology with genetics: a new tool for parsing cerebrovascular
      disease.

PMID- 24135527
TI  - Genetic susceptibility for ischemic infarction and arteriolosclerosis based on
      neuropathologic evaluations.
AB  - BACKGROUND: Recent genetic studies of stroke and related risk factors have
      identified a growing number of susceptibility loci; however, the relationship of
      these alleles to ischemic stroke is unknown. The challenge in finding
      reproducible loci of ischemic stroke susceptibility may be in part related to the
      etiologic heterogeneity in clinically defined stroke subtypes. In this study, we
      tested whether known single nucleotide polymorphisms (SNPs) associated with
      stroke or putative stroke risk factors are associated with neuropathologically
      defined micro- or macroscopic infarcts and with arteriolosclerosis. METHODS:
      Measures of neuropathology and genotyping were available from 755 deceased
      participants from the Religious Orders Study and the Rush Memory and Aging
      Project. All donated brains were examined by a board-certified neuropathologist
      using standardized protocol for the presence of microscopic infarct, macroscopic
      infarct and arteriolosclerosis (lipohyalinosis). In primary analysis, 74
      candidate SNPs previously associated (p < 5 * 10(-8)) with ischemic stroke or
      known risk factors, including atrial fibrillation (AF), hypertension, diabetes,
      low-density lipoprotein (LDL) level and carotid artery stenosis, were evaluated
      for association with neuropathologic endpoints. We performed a secondary
      exploratory analysis to include 93 additional SNPs associated with putative
      ischemic stroke risk factors including SNPs associated with high-density
      lipoprotein (HDL), triglyceride serum levels, myocardial infarction (MI),
      coronary artery disease and cerebral white matter disease. Regression models
      relating SNPs to cerebrovascular neuropathology were adjusted for age at death,
      gender and cohort membership. RESULTS: The strongest associations seen for both
      macroscopic and microscopic infarcts were risk variants associated with diabetes.
      The diabetes risk variant rs7578326 located near the IRS1 locus was associated
      with both macroscopic (OR = 0.73, p = 0.011) and microscopic (OR = 0.71, p =
      0.009) infarct pathology. Another diabetes susceptibility locus (rs12779790)
      located between the calcium/calmodulin-dependent protein kinase ID (CAMK1D) and
      cell division cycle 123 homolog (CDC123) genes is also associated with both
      macroscopic (OR = 1.40, p = 0.0292) and microscopic infarcts (OR = 1.43, p =
      0.0285). The diabetes risk variant rs864745 within JAZF1 was associated with
      arteriolosclerosis (OR = 0.80, p = 0.014). We observed suggestive associations
      with the diabetes risk variant rs7961581 (p = 0.038; between TSPAN8 and LGR5) and
      rs5215 (p = 0.043; KCNJ11), the LDL risk variant rs11206510 (p = 0.045; PCSK9),
      as well as the AF risk locus ZFHX3. The CDKN2A/B locus (rs2383207, 9p21),
      identified initially as a susceptibility allele for MI and recently implicated in
      large vessel stroke, was associated with macroscopic infarct pathology in our
      autopsy cohort (OR = 1.26, p = 0.031). CONCLUSION: Our results suggest
      replication of the candidate CDKN2A/B stroke susceptibility locus with directly
      measured macroscopic stroke neuropathology, and further implicate several
      diabetes and other risk variants with secondary, pleiotropic associations to
      stroke-related pathology in our autopsy cohort. When coupled with larger sample
      sizes, cerebrovascular neuropathologic phenotypes will likely be powerful tools
      for the genetic dissection of susceptibility for ischemic stroke.

PMID- 24135529
TI  - Risk of vascular events after nondisabling small and large vessel cerebral
      ischemia.
AB  - BACKGROUND: Small- and large-vessel disease (SVD and LVD, respectively) might
      have a different pathogenesis and prognosis but the long-term risk of death and
      recurrent stroke appears to be similar in previous studies. In this study, we
      investigated the long-term vascular prognosis of patients with LVD and SVD in a
      large cohort of well-documented patients. METHODS: We included 971 patients with
      transient ischemic attack (TIA) or nondisabling ischemic stroke of
      atherosclerotic origin referred to a university hospital in the Netherlands
      between 1994 and 2005 and followed them for the occurrence of vascular events or
      death. The primary outcome was a composite of stroke, myocardial infarction and
      vascular death, whichever happened first. Classification of SVD/LVD was primarily
      based on brain imaging. We used regression analyses to generate hazard ratios
      (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in
      subsets of the population, i.e. patients with subtype classification based on
      imaging, excluding TIA patients, first-ever stroke patients and LVD patients
      without a symptomatic carotid stenosis. RESULTS: During a mean follow-up of 6.3
      years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in
      128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56
      events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients
      (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular
      events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up
      period. When this risk was split into early risk (<1 year) and late risk (>1
      year), it was not significantly different for the 1-year risk of vascular events
      (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had
      fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For
      ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary
      outcome, here also the 1-year risk was not significantly different from >1-year
      risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively).
      The sensitivity analyses showed virtually the same results. CONCLUSION: In
      patients with nondisabling cerebrovascular disease, we found, despite no
      differences at baseline in terms of vascular risk factors, a better long-term
      prognosis for patients with LVD for all vascular events, especially for recurrent
      strokes. Our observations support a different pathogenesis in SVD and LVD
      patients, and optimal prevention is indicated for patients with what was formerly
      regarded as 'benign' SVD stroke.

PMID- 24135530
TI  - Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute
      ischemic stroke: new formulation and dosing regimen.
AB  - BACKGROUND AND PURPOSE: MCI-186 (edaravone) is a free radical scavenger approved
      in Japan since 2001 for the treatment of patients with acute ischemic stroke
      within 24 h from the onset of symptoms. It was recommended by the Japanese
      Guidelines for the Management of Stroke 2004. Our aim was to investigate the
      safety, tolerability and pharmacokinetics of a new formulation and dose regimen
      (intravenous bolus plus infusion) of MCI-186 suitable for the treatment of acute
      ischemic stroke in Europe because the Japanese treatment protocol includes twice
      a-day intravenous infusion of MCI-186 for a maximum of 14 days. Such a treatment
      protocol is not very practical in Europe, where hospital stay is much shorter in
      acute hospitals. METHODS: In a double-blind, placebo-controlled randomized
      clinical trial we studied two dosing regimens, each in a cohort of 18 patients.
      Patients were randomized in a 2:1 ratio in both cohorts to receive MCI-186 or
      placebo. Review of safety and plasma concentration data from the first cohort
      (loading dose 0.08 mg/kg + 0.2 mg/kg/h infusion) preceded the second cohort
      (loading dose 0.16 mg/kg + 0.4 mg/kg/h infusion). Safety parameters included
      adverse events, severe adverse events, physical examinations, local reactions at
      infusion site, ECG, clinical chemistry and hematology, modified Total Neuropathy
      Score and CT scans. RESULTS: Mean age and National Institutes of Health Stroke
      Scale (NIHSS) score on admission of patients in cohorts 1 and 2 and the placebo
      group were 64, 63, and 69 years and 5, 5, and 6, respectively. The number of
      treatment emergent adverse events that occurred was 109, most of which were
      transient, mild or moderate. Both doses of the new formulation and dosing regimen
      were well tolerated. After the initiation of the infusion, plasma concentrations
      of MCI-186 reached or exceeded prespecified target levels within 24 h in both MCI
      186 cohorts, which were in the putative therapeutic range in humans. Geometric
      mean values of MCI-186 plasma concentration at the end of the infusion in cohorts
      1 and 2 were 391 and 1,595 ng/ml, respectively. CONCLUSIONS: The primary
      objective of the present study, safety and tolerability of the new formulation
      and dosing regimen, was achieved. The new formula and both dosing regimens were
      well tolerated and achieved intended plasma concentrations suitable for larger
      safety studies before pivotal trials.

PMID- 24135531
TI  - Small deep infarction in patients with atrial fibrillation: evidence of lacunar
      pathogenesis.
AB  - BACKGROUND: It is difficult to clarify whether small deep infarction is caused by
      cardioembolism or intrinsic small vessel disease in patients with atrial
      fibrillation (AF). The purpose of this study was to determine whether preexisting
      small vessel disease would differ according to the presenting infarct pattern and
      to determine the factors associated with acute single small deep infarction in
      stroke patients with AF. METHODS: Between January 2008 and August 2012, 1,592
      consecutive patients with acute ischemic stroke presenting within 7 days of
      symptom onset were entered in a prospectively maintained stroke registry. For the
      present study, 231 stroke patients with AF were enrolled irrespective of the
      stroke subtype. We divided these patients into 2 groups (lacunar infarct pattern,
      n = 20, vs. nonlacunar infarct pattern, n = 211) according to the acute infarct
      pattern on diffusion-weighted imaging. Patients with acute single small deep
      infarction on diffusion-weighted imaging were assigned to the lacunar infarct
      pattern group. We assessed the severity of preexisting small vessel disease by
      grading white matter lesions (WMLs) according to the Fazekas scale
      (periventricular WML score ranging from 0 to 3 and deep WML score ranging from 0
      to 3 were added to give a total WML score ranging from 0 to 6), multilacunar
      state (number of chronic lacunes >=2) and the presence of microbleeds.
      Demographic characteristics, vascular risk factors and neuroimaging data were
      compared between the two groups. RESULTS: Patients with a lacunar infarct pattern
      showed more severe WMLs than those with a nonlacunar pattern [median total WML
      score 2.5 (range 2-4) vs. 1.0 (0-2); p < 0.001]. A multilacunar state was more
      prevalent in the lacunar infarct pattern group compared with the nonlacunar
      pattern group (65 vs. 28.9%; p = 0.001). However, the presence of microbleeds did
      not differ between the groups. Multiple logistic regression analyses revealed
      periventricular WMLs [odds ratio (OR) 4.12, 95% confidence interval (CI) 2.14
      7.92], deep WMLs (OR 3.42, 95% CI 1.75-6.66) and multilacunar state (OR 7.85, 95%
      CI 2.45-25.6) as the predictors of a lacunar infarct pattern. CONCLUSIONS: The
      severity of WMLs and chronic lacunes were independent predictors of the incident
      infarct pattern, which suggested that acute single small deep infarction might be
      caused by intrinsic small vessel disease despite the presence of concomitant AF.

PMID- 24135532
TI  - What does elevated high-sensitive troponin I in stroke patients mean: concomitant
      acute myocardial infarction or a marker for high-risk patients?
AB  - BACKGROUND: Acute ischemic stroke patients may occasionally suffer from
      concomitant acute coronary syndrome (ACS). Troponin I and T are established
      biomarkers to detect ACS. Recently introduced high-sensitive cardiac troponin (hs
      TNI and hs-TNT) assays are increasingly used to identify ACS in stroke patients
      even without signs or symptoms of ACS. These new test systems very often detect
      elevated values of hs-troponin, although clinical relevance and consequences of
      elevated hs-TNI values in these patients are unclear so far. PATIENTS AND
      METHODS: We examined hs-TNI values in 834 consecutive ischemic stroke patients
      admitted to our Comprehensive Stroke Center during a 1-year period. hs-TNI was
      measured immediately after admission and after 3 h if initial hs-TNI was elevated
      above the 99th percentile of normal values (>0.045 ng/ml). Patients with elevated
      values were divided into two groups: (1) constant and (2) dynamic hs-TNI values.
      The dynamic approach was defined as a 30% rise or fall of the hs-TNI value above
      the critical value within 3 h. All patients received stroke diagnostic and
      continuous monitoring according to international stroke unit standards, including
      a 12-lead ECG, blood pressure, body temperature and continuous ECG monitoring, as
      well as regular 6-hourly neurological and general physical examination (including
      NIHSS scores). The cardiologists - as members of the Stroke Unit team - evaluated
      clinical symptoms/examination, as well as laboratory, echocardiographic and ECG
      findings for the diagnosis of ACS. RESULTS: 172/834 (20.6%) patients showed
      elevated hs-TNI levels on admission. Patients with elevated hs-TNI values
      exhibited a significantly (p < 0.001) increased rate of hypertension (89 vs.
      77.2%), history of stroke (24.4 vs. 14.8%), history of coronary artery disease
      (65.7 vs. 34.1%), history of myocardial infarction (22.1 vs. 7.6%), heart failure
      (12.8 vs. 5.7%) and atrial fibrillation (44.2 vs. 23.6%). 82/136 patients showed
      constant and 54/136 patients dynamic hs-TNI values: among the latter, 5 patients
      were diagnosed with ST segment elevation myocardial infarction (STEMI) and 24
      with non-STEMI (NSTEMI). CONCLUSION: Our data demonstrate that hs-TNI was
      elevated in about 20.6% of acute ischemic stroke patients but therapeutically
      relevant ACS was diagnosed only in the dynamic group. hs-TNI elevations without
      dynamic changes may occur in stroke patients without ACS due to different reasons
      that stress the heart. Therefore, we suppose that hs-TNI is a sensitive marker to
      detect high-risk patients but serial measurements are mandatory and expert
      cardiological workup is essential for best medical treatment and to accurately
      diagnose ACS in acute ischemic stroke patients.

PMID- 24135533
TI  - Neurothrombectomy for the treatment of acute ischemic stroke: results from the
      TREVO study.
AB  - BACKGROUND: Fast recanalization has been shown to be one of the most important
      factors for good clinical outcome in stroke patients with acute large vessel
      occlusion. While intravenous thrombolysis has been shown to be of limited effect
      in patients with large clot burden, intra-arterial neurothrombectomy offers a new
      and promising possibility to achieve high recanalization rates within a short
      time. The Trevo device is a stent-like retriever and was primarily designed to
      remove thrombus in patients experiencing an acute ischemic stroke. We report on
      the results of the TREVO Study, which was a prospective, multicenter study in
      acute stroke patients treated with the Trevo device. METHODS: Patients were
      recruited in seven European centers under the control of an external monitor.
      Centers were selected because of their long experience with interventional stroke
      therapy especially with neurothrombectomy. We included adults aged 18-85 years
      with angiographically confirmed large vessel occlusion strokes and NIHSS scores
      of 8-30 and treatable within 8 h of symptom onset. The primary endpoint was
      revascularization, defined as at least TICI (thrombolysis in cerebral infarction)
      2a. The revascularization scores were assessed by an independent core lab.
      Secondary endpoints were clinical outcome at 90 days (mRS 90), any device-related
      serious adverse events and the rate of symptomatic intracerebral hemorrhages.
      RESULTS: 60 patients were enrolled. The overall recanalization rate (>=TICI 2a)
      was 91.7% and TICI 2b and 3 was achieved in 78.3%. At 90 days, 55% of the
      patients had a favorable neurological outcome (mRS 0-2) and 20% had died.
      Patients with successful recanalization (TICI 2a,b/3) had a good 90-day
      neurological outcome (mRS 0-2) in 60%, whereas no patient without recanalization
      had a mRS 90 <3. The overall rate of symptomatic intracerebral hemorrhage
      according to the SITS-MOST criteria was 5% (3/60). CONCLUSIONS: The study suggest
      that the Trevo StentrieverTM is a safe and effective device, which may offer the
      possibility of a high reperfusion rate and a high rate of patients with good
      clinical outcome after acute ischemic stroke due to proximal arterial occlusion.
      Randomized trials comparing intravenous thrombolysis with neurothrombectomy are
      now urgently needed to evaluate this new approach of interventional stroke
      therapy.

PMID- 24135534
TI  - TREVO pilot: an effective flight with a safe landing? No!

PMID- 24135535
TI  - Extra-intracranial standard bypass in the elderly: perioperative risk, bypass
      patency and outcome.
AB  - BACKGROUND: Patients with chronic atherosclerotic vessel occlusion and
      cerebrovascular hemodynamic insufficiency may benefit from extra-intracranial (EC
      IC) bypass surgery. Due to demographic changes, an increasing number of elderly
      patients presents with cerebrovascular hemodynamic insufficiency. So far, little
      data for EC-IC bypass surgery in elderly patients suffering occlusive
      cerebrovascular disease are available. We therefore designed a retrospective
      study to address the question whether EC-IC bypass is a safe and efficient
      treatment in a patient cohort >=70 years. METHODS: 50 patients underwent EC-IC
      standard bypass surgery with translocation of the superficial temporal artery to
      an M2 segment of the medial cerebral artery. Criteria for bypass surgery were
      presence of symptomatic occlusive cerebrovascular disease of the anterior
      circulation and proof of a severely restricted or abrogated reserve capacity
      (detected by H2O-photon emission tomography or single photon emission computer
      tomography - before and after forced vessel dilatation by diamox). The incidence
      of perioperative neurological and surgical complications, bypass patency, bypass
      function and short-term outcome were retrospectively analyzed. RESULTS: The study
      cohort consisted of 16 patients >=70 years (mean = 74.3 years, SE 1.3). It was
      compared to a cohort of 34 patients <70 years (mean = 61.2 years, SE 1.0). Both
      groups underwent EC-IC bypass surgery after careful preoperative work-up. Both
      patient groups did not differ significantly in gender, vascular pathology,
      previous history of diseases/comorbidity or clinical symptoms. The number of
      patients which underwent stenting or other endovascular treatments of the
      internal or common carotid artery prior to EC-IC bypass surgery was significantly
      higher in the group of patients >=70 years (37.5 vs. 0%, p < 0.001).
      Perioperative stroke rate was 0% in both groups and mild morbidity occurred in
      18.8 and 14.7%, respectively (p = 0.699). One 84-year-old female patient died due
      to perioperative endocarditis. Initial bypass patency was 93.8% in patients above
      the age of 70 years and 97.1% in the younger group (p = 0.542). Secondary
      occlusion rate was low in both groups (>=70 years: 0% vs. <70 years 3.7%). No new
      neurologic deficit occurred in patients with a patent bypass during the follow-up
      period (median 18 +/- 13.1 months). Two patients with an initially occluded
      bypass and one with a secondary bypass occlusion suffered from new neurological
      symptoms. CONCLUSIONS: Our data show comparable safety and efficiency of EC-IC
      bypass surgery in patients under and above the age of 70 years due to a careful
      preoperative work-up and a strict indication for bypass surgery.

PMID- 24135536
TI  - Gene expression profile of blood cells for the prediction of delayed cerebral
      ischemia after intracranial aneurysm rupture: a pilot study in humans.
AB  - BACKGROUND: Delayed cerebral ischemia (DCI) is a potentially devastating
      complication after intracranial aneurysm rupture and its mechanisms remain poorly
      elucidated. Early identification of the patients prone to developing DCI after
      rupture may represent a major breakthrough in its prevention and treatment. The
      single gene approach of DCI has demonstrated interest in humans. We hypothesized
      that whole genome expression profile of blood cells may be useful for better
      comprehension and prediction of aneurysmal DCI. METHODS: Over a 35-month period,
      218 patients with aneurysm rupture were included in this study. DCI was defined
      as the occurrence of a new delayed neurological deficit occurring within 2 weeks
      after aneurysm rupture with evidence of ischemia either on perfusion-diffusion
      MRI, CT angiography or CT perfusion imaging, or with cerebral angiography. DCI
      patients were matched against controls based on 4 out of 5 criteria (age, sex,
      Fisher grade, aneurysm location and smoking status). Genome-wide expression
      analysis of blood cells obtained at admission was performed by microarrays.
      Transcriptomic analysis was performed using long oligonucleotide microarrays
      representing 25,000 genes. Quantitative PCR: 1 ug of total RNA extracted was
      reverse-transcribed, and the resulting cDNA was diluted 10-fold before performing
      quantitative PCR. Microarray data were first analyzed by 'Significance Analysis
      of Microarrays' software which includes the Benjamini correction for multiple
      testing. In a second step, microarray data fold change was compared using a two
      tailed, paired t test. Analysis of receiver-operating characteristic (ROC) curves
      and the area under the ROC curves were used for prediction analysis. Logistic
      regression models were used to investigate the additive value of multiple
      biomarkers. RESULTS: A total of 16 patients demonstrated DCI. Significance
      Analysis of Microarrays software failed to retrieve significant genes, most
      probably because of the heterogeneity of the patients included in the microarray
      experiments and the small size of the DCI population sample. Standard two-tailed
      paired t test and C-statistic revealed significant associations between gene
      expression and the occurrence of DCI: in particular, the expression of
      neuroregulin 1 was 1.6-fold upregulated in patients with DCI (p = 0.01) and
      predicted DCI with an area under the ROC curve of 0.96. Logistic regression
      analyses revealed a significant association between neuroregulin 1 and DCI (odds
      ratio 1.46, 95% confidence interval 1.02-2.09, p = 0.02). CONCLUSIONS: This pilot
      study suggests that blood cells may be a reservoir of prognostic biomarkers of
      DCI in patients with intracranial aneurysm rupture. Despite an evident lack of
      power, this study elicited neuroregulin 1, a vasoreactivity-, inflammation- and
      angiogenesis-related gene, as a possible candidate predictor of DCI. Larger
      cohort studies are needed but genome-wide microarray-based studies are promising
      research tools for the understanding of DCI after intracranial aneurysm rupture.

PMID- 24135537
TI  - Spontaneous middle cerebral artery dissection demonstrated by high-resolution T1
      weighted 3D image.

PMID- 24135538
TI  - Cerebral amyloid angiopathy and transient focal neurological episodes.

PMID- 24135540
TI  - Applications of justification and optimization in medical imaging: examples of
      clinical guidance for computed tomography use in emergency medicine.
AB  - Availability, reliability, and technical improvements have led to continued
      expansion of computed tomography (CT) imaging. During a CT scan, there is
      substantially more exposure to ionizing radiation than with conventional
      radiography. This has led to questions and critical conclusions about whether the
      continuous growth of CT scans should be subjected to review and potentially
      restraints or, at a minimum, closer investigation. This is particularly pertinent
      to populations in emergency departments, such as children and patients who
      receive repeated CT scans for benign diagnoses. During the last several decades,
      among national medical specialty organizations, the American College of Emergency
      Physicians and the American College of Radiology have each formed membership
      working groups to consider value, access, and expedience and to promote broad
      acceptance of CT protocols and procedures within their disciplines. Those efforts
      have had positive effects on the use criteria for CT by other physician groups,
      health insurance carriers, regulators, and legislators. 

PMID- 24135541
TI  - Upconversion nanoparticle-based Forster resonance energy transfer for detecting
      the IS6110 sequence of Mycobacterium tuberculosis complex in sputum.
AB  - Upconversion nanoparticles (UCNPs), which are excited at near-infrared wavelength
      (980 nm), emit high-energy photons. Since UCNPs display a high signal-to-noise
      ratio and no photobleaching, they are extremely useful for diagnostic
      application. In this study, we applied UCNPs for detecting the IS6110 sequence of
      the Mycobacterium tuberculosis complex (MTBC) and evaluated the feasibility of
      the system for use in molecular diagnostics. Using biotinylated primers, IS6110
      DNA PCR was performed and the PCR amplicon was then mixed with streptavidin
      conjugated UCNPs, followed by intercalation with SYTOX Orange dye. Fluorescence
      detection for the Forster resonance energy transfer (FRET) of the UCNPs (UCNP
      FRET) was then performed. The estimated lowest detection by UCNP-FRET was 10(2)
      copies/MUL of IS6110 DNA (157 bp). The kappa agreement of the UCNP-FRET assay
      with conventional PCR was 0.8464 (95% confidence interval, 0.7442-0.9486) and
      false-negative results were reduced. Our results demonstrated the successful
      implementation of the UCNP-FRET system in detecting the IS6110 sequence of the
      MTBC and its potential application for molecular diagnostics.

PMID- 24135542
TI  - Selective capture of human red blood cells based on blood group using long-range
      surface plasmon waveguides.
AB  - An optical biosensor based on long-range surface plasmon-polariton waveguides is
      applied to the detection of blood group antigen A on whole erythrocytes. The
      biosensor consists of straight gold waveguides embedded in CYTOP with an etched
      fluidic channel. The gold waveguides were functionalized with immunoglobulin G
      against blood group A (anti-A IgG) by forming a self-assembled monolayer (SAM) of
      16-mercaptohexadecanoic acid (16-MHA) and then conjugating the anti-A IgG through
      carbodiimide chemistry. In order to demonstrate anti-A surface selectivity,
      solutions of O-type, B-type, A-type and AB-type red blood cells (RBCs) were
      sequentially injected over an anti-A functionalized waveguide. Surfaces were
      regenerated by lysing attached cells with distilled/deionized water (DDI H2O).
      The efficiency of surface regeneration with DDI H2O was very high as determined
      by performing six sequential binding/regeneration cycles of A RBC capture on the
      same anti-A surface. Also, five solutions of different A RBC concentrations,
      ranging from 1.14 * 10(5)cells/ml to 1.83 * 10(6)cells/ml, were injected over an
      anti-A surface to determine the limit of detection (LOD), which was found to be
      less than 3 * 10(5)cells/ml. Finally, the response produced by a single cell
      bound to a waveguide was determined by relating the number of bound cells to the
      response produced, from which the signal-to-noise ratio for single cell detection
      was determined to be ~95. The waveguides are promising as simple, low-cost and
      compact transducers, functionalized using standard thiol-based chemistries, for
      the selective detection of cells.

PMID- 24135543
TI  - Rapid pathogen detection with bacterial-assembled magnetic mesoporous silica.
AB  - We report rapid and accurate pathogen detection by coupling with high efficiency
      magnetic separation of pathogen by Ni(2+)-heterogeneous magnetic mesoporous
      silica (Ni-HMMS) and real time-polymerase chain reaction (RT-PCR) technique. Ni
      HMMS was developed with a significant incorporation of Fe particles within the
      silica mesopores by programmed thermal hydrogen reaction and functionalized with
      Ni(2+) ion on the surface by the wet impregnation process. High abundant Ni(2+)
      ions on the Ni-HMMS surface were able to assemble with cell wall component
      protein NikA (nickel-binding membrane protein), which contains several pathogenic
      bacteria including Escherichia coli O157:H7. NikA protein expression experiment
      showed the outstanding separation rate of the nikA gene-overexpressed E. coli
      (pSY-Nik) when comparing with wild-type E. coli (44.5 +/- 13%) or not over
      expressed E. coli (pSY-Nik) (53.2 +/- 2.7%). Moreover, Ni-HMMS showed lower
      obstacle effect by large reaction volume (10 mL) than spherical core/shell-type
      silica magnetic nanoparticles functionalized with Ni(2+) (ca. 40 nm-diameters).
      Finally, the Ni-HMMS was successfully assessed to separate pathogenic E. coli
      O157:H7 and applied to direct and rapid RT-PCR to quantitative detection at
      ultralow concentration (1 Log10 cfu mL(-1)) in the real samples (milk and
      Staphylococcus aureus culture broth) without bacterial amplification and DNA
      extraction step.

PMID- 24135544
TI  - Exhaled breath analysis with electronic nose technology for detection of acute
      liver failure in rats.
AB  - The aim of this study was to assess the classification accuracy of an e-Nose in
      detecting acute liver failure (ALF) in rats. Exhaled breath from 14 rats was
      repeatedly sampled by e-Nose (8 sensors) and an additional external CO2 sensor at
      three stages: healthy period; portacaval shunt; and during the development of ALF
      due to surgically induced complete liver ischemia. We performed principal
      component analysis (PCA) on the (grouped) sensor data in each stage and the
      classification accuracy of the first two principal components was assessed by the
      leave-one-out approach. In addition we performed gas chromatography-mass
      spectrometry (GC-MS) analysis of the exhaled breath from three rats. The first
      and second principal components from the PCA analysis of e-Nose data accounted
      for more than 95% variance in the data. Measurements in the ALF stage were
      contrasted with the measurements in the control stage. Leave-one-out validation
      showed classification accuracy of 96%. This accuracy was reached after 3h of ALF
      development, and was reached already after 2h when data of an external CO2 sensor
      were also included. GC-MS identified 2-butanol, 2-butanone, 2-pentanone and 1
      propanol to be possibly elevated in the ALF stage. This is the first study to
      demonstrate that ALF in rats can be detected by e-Nose data analysis of the
      exhaled breath. Confirmation of these results in humans will be an important step
      forward in the non-invasive diagnosis of ALF. 

PMID- 24135545
TI  - Activity-dependent hyperpolarization of EGABA is absent in cutaneous DRG neurons
      from inflamed rats.
AB  - A shift in GABA(A) signaling from inhibition to excitation in primary afferent
      neurons appears to contribute to the inflammation-induced increase in afferent
      input to the CNS. An activity-dependent depolarization of the GABA(A) current
      equilibrium potential (E(GABA)) has been described in CNS neurons which drives a
      shift in GABA(A) signaling from inhibition to excitation. The purpose of the
      present study was to determine if such an activity-dependent depolarization of
      E(GABA) occurs in primary afferents and whether the depolarization is amplified
      with persistent inflammation. Acutely dissociated retrogradely labeled cutaneous
      dorsal root ganglion (DRG) neurons from naive and inflamed rats were studied with
      gramicidin perforated patch recording. Rather than a depolarization, 200 action
      potentials delivered at 2 Hz resulted in a ~10 mV hyperpolarization of E(GABA) in
      cutaneous neurons from naive rats. No such hyperpolarization was observed in
      neurons from inflamed rats. The shift in E(GABA) was not blocked by 10 MUM
      bumetanide. Furthermore, because activity-dependent hyperpolarization of E(GABA)
      was fully manifest in the absence of HCO3- in the bath solution, this shift was
      not dependent on a change in HCO3--Cl- exchanger activity, despite evidence of
      HCO3--Cl- exchangers in DRG neurons that may contribute to the establishment of
      E(GABA) in the presence of HCO3-. While the mechanism underlying the activity
      dependent hyperpolarization of E(GABA) has yet to be identified, because this
      mechanism appears to function as a form of feedback inhibition, facilitating GABA
      mediated inhibition of afferent activity, it may serve as a novel target for the
      treatment of inflammatory pain.

PMID- 24135546
TI  - Intramural hematoma detection by susceptibility-weighted imaging in intracranial
      vertebral artery dissection.
AB  - BACKGROUND: The radiologic diagnosis of vertebral artery dissection (VAD) depends
      on characteristic intraluminal findings on angiography and intramural hematoma or
      a double-lumen sign on high-resolution vessel wall imaging. We aimed to evaluate
      the accuracy of intramural hematoma sign on susceptibility-weighted imaging (SWI)
      in VAD. METHODS: We retrospectively analyzed SWI, phase map images and brain
      computed tomography (CT) of the consecutive patients who suffered an ischemic
      stroke in the vertebral artery territory from August 2010 to July 2012. We
      divided the patients into 2 groups: the VAD group and the nondissection group.
      VAD was diagnosed by conventional catheter angiographic findings (aneurysmal
      dilatation, pearl-and-string or tapered steno-occlusion) and pathognomonic
      findings such as intramural hematoma or a double-lumen sign on the source images
      of TOF-MRA, high-resolution T1-weighted MRI or high-resolution T2-weighted MRI.
      Intramural hematoma sign was considered positive if the patient had an eccentric
      or concentric hypointense signal lesion in the vertebral artery on SWI, a
      corresponding hyperintense signal on phase map and no evidence of calcification
      on the brain CT, suggesting blood products other than calcification. Two
      experienced neuroradiologists blinded to clinical information and angiographic
      findings were asked to judge for the presence of intramural hematoma sign on SWI.
      The accuracy of intramural hematoma sign on SWI was evaluated. Phase value,
      demographic and clinical data were compared between the VAD and the nondissection
      groups. RESULTS: Thirty-nine patients were included: 10 in the VAD group and 29
      in the non-dissection group. Among the VAD group cases, intramural hematoma sign
      on SWI was positive in 9 of the 10 VAD cases and in 1 out of the 29 cases in the
      nondissection group. The intramural hematoma sign on SWI was significantly
      associated with VAD (p < 0.001), and showed sensitivity of 90% and specificity of
      96.6%. Mean phase values of intramural hematomas (n = 9) were all positive and
      those of calcified lesions (n = 13) were all negative (0.45 radian vs. -0.42
      radian, p < 0.001). CONCLUSIONS: The intramural hematoma sign on SWI was
      significantly associated with VAD and the phase map values were higher in
      intramural hematomas when compared with atherosclerotic calcifications.

PMID- 24135547
TI  - Mycobacterium bovis infections in domesticated non-bovine mammalian species. Part
      2: A review of diagnostic methods.
AB  - Despite the large host range of Mycobacterium bovis, ante-mortem diagnostic tests
      for the infection mostly lack sensitivity/specificity and/or remain unvalidated
      in non-bovine species. The epidemiology and importance of M. bovis infection in
      these species are discussed in the first part of this two-part review. This
      second part focuses on the diagnostic options available to identify infected
      species such as sheep, goats, dogs, cats, and camelids, and highlights the
      significant challenges posed, both in establishing estimates of disease
      prevalence and in controlling infections in these species, in the absence of
      fully validated tests. 

PMID- 24135548
TI  - Effects of in utero pestivirus infection on bovine fetal bone geometry,
      biomechanical properties and composition.
AB  - Transplacental viral infection of the fetus can result in abnormal trabecular and
      cortical bone modeling in long bones through impaired bone resorption and
      formation. Although such infections are frequently associated with neonatal
      fractures in humans and animals, their effect on the biomechanical properties of
      the developing skeleton remain poorly understood. The goal of this study was to
      determine the effects of transplacental bovine viral diarrhea virus (BVDV)
      infection on the biomechanical properties of fetal femora. Pregnant heifers were
      inoculated intranasally with non-cytopathic BVDV or media alone on day 75 of
      gestation to produce persistently infected (PI) and control fetuses,
      respectively, which were then removed on days 192 and 245 of gestation.
      Histomorphometry, compositional analysis and 'four-point bending until failure'
      were performed on fetal femora. Altered cortical geometry largely accounted for
      differences in calculated elastic modulus (PI vs. control, and day 192 vs. day
      245) and ultimate stress (day 192 vs. day 245). Fetal infection with BVDV did not
      significantly impair inherent biomechanical properties of bone but rather
      resulted in decreased periosteal apposition rates, manifested as smaller femoral
      mid-diaphyseal diameters. There were no differences between PI and control
      fetuses in cortical thickness ratio, ash density or calcium/phosphorous content;
      however, cortical thickness ratio decreased with fetal age. Thus even when
      cortical thickness ratios are similar, differences in mid-diaphyseal diameter
      affect the error associated with the calculation of stress and strain by
      classical beam theory equations. 

PMID- 24135549
TI  - An unholy disease in the Holy Land: the history of anthrax between the Jordan
      River and the Mediterranean Sea (1909-2012).
AB  - The history of recorded cases of anthrax in human beings and animals from 1909 to
      2012 in the area between the Jordan River and the Mediterranean Sea is reviewed.
      The disease was endemic until the middle of the 20th century, but the incidence
      decreased thereafter, with only sporadic cases from the 1980s onwards. Human
      cases have not been diagnosed in the region since 1984 and the number of episodes
      of animal disease has reduced to less than one per year. This decline is mostly
      due to the disruption of the infective cycle by improved veterinary control,
      including vaccination, treatment and outbreak management. A policy of reactive
      vaccination for 10 years of affected herds and herds grazing in their proximity
      has been applied. No new outbreaks have been observed in such herds after the
      cessation of vaccination, despite continued grazing on the same sites, so it is
      assumed that spore survival in such areas is shorter than 10 years. This is
      independent of the soil composition, which is calcareous throughout most of the
      relevant area. However, reemergence of anthrax, even after decades, has occurred
      following disturbance and heavy rainfall.

PMID- 24135550
TI  - Dynamic waste management (DWM): towards an evolutionary decision-making approach.
AB  - To guarantee sustainable and dynamic waste management, the dynamic waste
      management approach (DWM) suggests an evolutionary new approach that maintains a
      constant flow towards the most favourable waste treatment processes (facilities)
      within a system. To that end, DWM is based on the law of conservation of energy,
      which allows the balancing of a network, while considering the constraints of
      incoming (h1 ) and outgoing (h2 ) loads, as well as the distribution network
      (DeltaH) characteristics. The developed approach lies on the identification of
      the prioritization index (PI) for waste generators (analogy to h1 ), a global
      allocation index for each of the treatment processes (analogy to h2 ) and the
      linear index load loss (DeltaH) associated with waste transport. To demonstrate
      the scope of DWM, we outline this approach, and then present an example of its
      application. The case study shows that the variable monthly waste from the three
      considered sources is dynamically distributed in priority to the more favourable
      processes. Moreover, the reserve (stock) helps temporarily store waste in order
      to ease the global load of the network and favour a constant feeding of the
      treatment processes. The DWM approach serves as a decision-making tool by
      evaluating new waste treatment processes, as well as their location and new means
      of transport for waste. 

PMID- 24135551
TI  - Gender differences in depression and anxiety: the role of age.
AB  - Although females run greater risk for affective disorders, the greater
      vulnerability of women for these disorders varies with the age. The present study
      evaluates the lifetime incidence of depressive and anxiety disorders by age and
      gender in a community sample (2363 subjects; 54.6% females), representative of
      the general population (Sesto Fiorentino Study). Lifetime prevalence of affective
      disorders resulted higher in females. The age-sex pattern for affective disorders
      was observed only before menopause. 

PMID- 24135552
TI  - Poor savouring and low self-efficacy are predictors of anhedonia in patients with
      schizophrenia spectrum disorders.
AB  - Previous research suggests that negative schizotypes may be impaired in their
      ability to savour pleasant events (Applegate et al., 2009) and that schizophrenia
      patients believe that everyday tasks are excessively difficult to complete so
      that they attempt these tasks less frequently (MacCarthy et al., 1986; Bentall et
      al., 2010). It is possible that these beliefs and behaviours underpin negative
      symptoms such as anhedonia, avolition, apathy and associality. In the present
      study, 50 schizophrenia patients and 100 matched controls (half employed and half
      unemployed) completed self-report measures of self-efficacy and savouring.
      Patients reported savouring past, present and future events less than employed
      and unemployed groups, irrespective of mood state and I.Q. Patients also rated
      everyday tasks as more difficult to master. Inpatients compared to outpatients
      rated tasks more difficult but less important although they did not differ on the
      savouring measure. Abnormal judgements of difficulty and the reduced propensity
      to mentally rehearse past or future positive experiences to up-regulate mood
      could explain negative symptom patients' lack of engagement in everyday
      activities and eventual social withdrawal. These findings suggest the need to
      develop cognitive-behavioural savouring and self-efficacy interventions for
      patients experiencing the negative symptoms of schizophrenia. 

PMID- 24135553
TI  - The effect of focused attention and open monitoring meditation on attention
      network function in healthy volunteers.
AB  - Mindfulness meditation techniques are increasingly popular both as a life-style
      choice and therapeutic adjunct for a range of mental and physical health
      conditions. However, little is known about the mechanisms through which
      mindfulness meditation and its constituent practices might produce positive
      change in cognition and emotion. Our study directly compared the effects of
      Focused Attention (FA) and Open-Monitoring (OM) meditation on alerting, orienting
      and executive attention network function in healthy individuals. Participants
      were randomized to three intervention groups: open-focused meditation, focused
      attention, and relaxation control. Participants completed an emotional variant of
      the Attention Network Test (ANT) at baseline and post-intervention. OM and FA
      practice improved executive attention, with no change observed in the relaxation
      control group. Improvements in executive attention occurred in the absence of
      change in subjective/self-report mood and cognitive function. Baseline levels of
      dispositional/trait mindfulness were positively correlated with executive control
      in the ANT at baseline. Our results suggest that mindfulness meditation might
      usefully target deficits in executive attention that characterise mood and
      anxiety disorders. 

PMID- 24135554
TI  - High dietary salt decreases antioxidant defenses in the liver of fructose-fed
      insulin-resistant rats.
AB  - In this study we investigated the hypothesis that a high-salt diet to
      hyperinsulinemic rats might impair antioxidant defense owing to its involvement
      in the activation of sodium reabsorption to lead to higher oxidative stress. Rats
      were fed a standard (CON), a high-salt (HS), or a high-fructose (HF) diet for 10
      weeks after which, 50% of the animals belonging to the HF group were switched to
      a regimen of high-fructose and high-salt diet (HFS) for 10 more weeks, while the
      other groups were fed with their respective diets. Animals were then euthanized
      and their blood and liver were examined. Fasting plasma glucose was found to be
      significantly higher (approximately 50%) in fructose-fed rats than in the control
      and HS rats, whereas fat liver also differed in these animals, producing
      steatosis. Feeding fructose-fed rats with the high-salt diet triggered
      hyperinsulinemia and lowered insulin sensitivity, which led to increased levels
      of serum sodium compared to the HS group. This resulted in membrane perturbation,
      which in the presence of steatosis potentially enhanced hepatic lipid
      peroxidation, thereby decreasing the level of antioxidant defenses, as shown by
      GSH/GSSG ratio (HFS rats, 7.098+/-2.1 versus CON rats, 13.2+/-6.1) and superoxide
      dismutase (HFS rats, 2.1+/-0.05 versus CON rats, 2.3+/-0.1%), and catalase (HFS
      rats, 526.6+/-88.6 versus CON rats, 745.8+/-228.7 U/mg ptn) activities. Our
      results indicate that consumption of a salt-rich diet by insulin-resistant rats
      may lead to regulation of sodium reabsorption, worsening hepatic lipid
      peroxidation associated with impaired antioxidant defenses. 

PMID- 24135555
TI  - Enteral leptin administration affects intestinal autophagy in suckling piglets.
AB  - Leptin has been shown to play an integral role in the endocrine regulation of
      metabolism. Moreover, a substantial amount of this peptide has been found in
      colostrum and milk. The aim of the study was to investigate the effects of
      exogenous leptin, administered intragastrically, on the process of autophagy and
      the changes in cell hyperplasia and hypertrophy in the small intestine mucosa.
      Three groups (n = 6) of neonatal piglets were used in the study. The pigs were
      fed either by their sows (sow-reared piglets) or with only milk formula, or with
      milk formula together with leptin administered via a stomach tube (10 MUg/kg BW)
      every 8 h for 6 d. We have shown that pure milk formula feeding significantly
      elevates (P < 0.05) autophagy compared with that observed in sow-reared piglets.
      Compared with the control group, feeding milk formula supplemented with leptin
      resulted in a significant decrease (P < 0.05) in immunodetection of microtubule
      associated protein 1 light chain 3, as well as significantly accelerated
      epithelial cell renewal (P < 0.05). We demonstrated that autophagy is involved in
      the remodeling of the small intestine mucosa and that leptin, when administered
      enterally, may be an important factor for its regulation. 

PMID- 24135556
TI  - Achilles tendinopathy management: A pilot randomised controlled trial comparing
      platelet-richplasma injection with an eccentric loading programme.
AB  - OBJECTIVES: To conduct a pilot randomised controlled trial to evaluate the
      feasibility of conducting a larger trial to evaluate the difference in Victorian
      Institute of Sports Assessment-Achilles (VISA-A) scores at six months between
      patients with Achilles tendinopathy treated with a platelet-rich plasma (PRP)
      injection compared with an eccentric loading programme. METHODS: Two groups of
      patients with mid-substance Achilles tendinopathy were randomised to receive a
      PRP injection or an eccentric loading programme. A total of 20 patients were
      randomised, with a mean age of 49 years (35 to 66). All outcome measures were
      recorded at baseline, six weeks, three months and six months. RESULTS: The mean
      VISA-A score for the injection group at the primary endpoint of six months was
      76.0 (95% confidence interval (CI) 58.3 to 93.7) and for the exercise group was
      57.4 (95% CI 38.1 to 76.7). There was no statistically significant difference
      between these scores (p = 0.171), which was expected from such a pilot study.
      CONCLUSIONS: This pilot study has been key to providing data to inform a larger
      study and shows that the methodology is feasible. Cite this article: Bone Joint
      Res 2013;2:227-32.

PMID- 24135557
TI  - Polypoidal choroidal vasculopathy exudation and hemorrhage: results of monthly
      ranibizumab therapy at one year.
AB  - PURPOSE: To evaluate the efficacy and safety of monthly intravitreal injections
      of ranibizumab in patients with polypoidal choroidal vasculopathy (PCV) and
      active exudation or hemorrhage. METHODS: A prospective, single practice, open
      label trial of monthly intravitreal ranibizumab (0.5 mg) injections for PCV in 13
      eyes of 13 patients who completed the 1-year study. The primary outcome measure
      was stabilization of vision (loss of <15 ETDRS letters). Secondary outcome
      measures included incidence of ocular and systemic adverse events, changes in
      subretinal hemorrhage, central foveal thickness, and polypoidal complexes on
      indocyanine green angiography at 1 year. RESULTS: No patient lost >= 15 letters
      in visual acuity at 1 year. Three patients (23%) gained >= 15 letters at 12
      months. Subretinal hemorrhage resolved in 9/9 eyes (100%). Macular edema improved
      in 5/5 eyes (100%). Subretinal fluid completely resolved in 4/9 eyes (44%),
      decreased in 2/9 eyes (22%), and increased in 3/9 eyes (33%). Polypoidal
      complexes decreased in 5/13 eyes (38%). CONCLUSION: Continuous monthly
      intravitreal ranibizumab decreases leakage and hemorrhage in eyes with exudative
      and hemorrhagic complications of PCV. Branching vascular networks persisted, and
      polypoidal complexes decreased in only 5/13 (38%) eyes with continuous
      antiangiogenic therapy at 1 year.

PMID- 24135558
TI  - Factors associated with early recanalization failure following intravenous rt-PA
      therapy for ischemic stroke.
AB  - BACKGROUND: Although intravenous recombinant tissue-type plasminogen activator
      (rt-PA) therapy can be effective for ischemic stroke, a considerable percentage
      of patients do not receive any benefit as a result of early recanalization
      failure. We aimed to investigate the factors associated with early recanalization
      failure following intravenous rt-PA therapy. METHODS: Patients with acute
      ischemic stroke and internal carotid artery (ICA) or middle cerebral artery
      occlusion on initial magnetic resonance angiography (MRA) who received
      intravenous rt-PA therapy within 3 h of stroke onset and underwent follow-up MRA
      within 8 h after treatment were enrolled. Baseline characteristics, stroke
      features, onset to treatment time, initial National Institutes of Health Stroke
      Scale (NIHSS) score, initial Alberta Stroke Programme Early CT Score on diffusion
      weighted imaging-ASPECTS (Alberta Stroke Program Early Computed Tomography
      Score), the presence of ICA or M1 origin (the residual length <5 mm) (ICA/M1
      origin occlusion), initial vital signs, and laboratory findings were recorded.
      Early recanalization on the follow-up MRA within 8 h was evaluated by modified
      Mori grade: grade 0, no reperfusion; grade 1, movement of thrombus; grade 2,
      partial recanalization, and grade 3, complete recanalization. RESULTS: Seventy
      subjects (35 women, 77 +/- 12 years) were enrolled. The median (interquartile
      range: IQR) NIHSS score was 18 (12.5-24), and the mean onset to treatment time
      was 141 +/- 54 min. ICA was occluded in 29%, M1 origin in 17%, M1 middle in 13%,
      M1 distal in 26% and M2 in 15%. The median (IQR) pretreatment diffusion weighted
      imaging-ASPECTS was 8 (6-9), and follow-up time of MRA was 65 min (59-70) after
      rt-PA therapy. Thirty-two subjects (46%) showed modified Mori grade 0; 10 (14%),
      grade 1; 9 (13%), grade 2, and 19 (27%), grade 3. Multivariate analyses revealed
      ICA/M1 origin occlusion (OR 3.71, 95% CI 1.03-14.87, p = 0.044), and C-reactive
      protein (per 0.1-mg/dl increment, OR 1.19, 95% CI 1.03-1.44, p = 0.013) were
      independently associated with subjects with no recanalization (grade 0-1),
      whereas age (per years old, OR 0.93, 95% CI 0.86-0.99, p = 0.014) and high
      density lipoprotein cholesterol (per 1-mg/dl increment, OR 0.94, 95% CI 0.89
      0.98, p = 0.004) were inversely associated with those. CONCLUSION: ICA/M1 origin
      occlusion and C-reactive protein were positively and high-density lipoprotein
      cholesterol was negatively associated with early recanalization failure.

PMID- 24135559
TI  - Treatment of unresectable squamous cell carcinoma of the skin with epidermal
      growth factor receptor antibodies--a case series.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC), including squamous cell carcinoma
      (SCC) and basal cell carcinoma (BCC), is the most common malignancy. Unresectable
      or metatstatic SCC is rare and therapy can be difficult because of advanced age
      and comorbidities. Targeted therapy with monoclonal antibodies (mAbs) against
      EGFR is an option in these patients. OBJECTIVE: The aim of this presentation is
      to provide additional evidence on the safety of anti-EGFR mAbs in long-term
      palliation and adjuvant treatment of advanced SCC. MATERIALS AND METHODS: This is
      a retrospective analysis of 4 patients with locally advanced or metastatic SCC
      who received cetuximab and/or panitumumab. RESULTS: 3 patients (2 females, 1
      male, ages 86 to 93) received cetuximab for the treatment of unresectable SCC. In
      2 patients partial remissions were achieved and maintained with continuous
      treatment for 17 and 18 months. Another patient achieved complete remission after
      16 cetuximab treatments and is still free of disease with ongoing therapy after
      an overall observation period of 16 months. In a fourth patient, with recurrent
      loco-regional metastatic disease of the scalp and neck, adjuvant cetuximab
      followed by panitumumab was introduced after extensive surgery. 2 patients had a
      grade II-III skin rash successfully treated with topical erythromycin, systemic
      doxycyclin and dose modification. CONCLUSION: Cetuximab is suitable for
      palliation in elderly patients, able to maintain remissions and prevent disease
      progression over extended periods of continuing treatment without significant
      toxicity. Furthermore, adjuvant anti-EGFR therapy may be a promising treatment
      strategy in patients with a high risk of recurrence.

PMID- 24135560
TI  - Taking ergonomics to the bedside--a multi-disciplinary approach to designing
      safer healthcare.
AB  - A multi-disciplinary approach to designing safer healthcare was utilised to
      investigate risks in the bed-space in elective surgical wards. The Designing Out
      Medical Error (DOME) project brought together clinicians, designers,
      psychologists, human factors and business expertise to develop solutions for the
      highest risk healthcare processes. System mapping and risk assessment techniques
      identified nearly 200 potential failure modes in hand hygiene, isolation of
      infection, vital signs monitoring, medication delivery and handover of
      information. Solutions addressed issues such as the design of equipment,
      reminders, monitoring, feedback and standardisation. Some of the solutions, such
      as the CareCentreTM, which brings many of the processes and equipment together
      into one easy to access workstation at the foot of the bed, have been taken
      forward to clinical trials and manufacture. The project showed the value of the
      multi-disciplinary and formal human factors approaches to healthcare design for
      patient safety. In particular, it demonstrates the application of human factors
      to a complete design cycle and provides a case study for the activities required
      to reach a safe, marketable product. 

PMID- 24135561
TI  - Longitudinal trends in hedonic hunger after Roux-en-Y gastric bypass in
      adolescents.
AB  - BACKGROUND: Initial outcome studies have reported that Roux-en-Y gastric bypass
      (RYGB) is safe and efficacious for adolescents with extreme obesity. Although
      rapid weight loss is seen initially, data also show that modest weight regain
      typically occurs as early as the second postoperative year. The contribution of
      various psychological factors, including hedonic hunger, to postoperative weight
      regain has not previously been studied in adolescents. The objective of this
      study was to examine the variability in hedonic hunger and body mass index (BMI)
      over the initial 2-year period of weight loss and modest weight regain in
      adolescent RYGB recipients. METHODS: A total of 16 adolescents completed the
      Power of Food Scale before surgery and at 3, 6, 12, 18, and 24 months
      postoperatively. Height and weight were measured at each time point, from which
      BMI was calculated. RESULTS: Nonlinear trends were observed for time on both
      overall hedonic hunger and hedonic hunger specifically related to food available
      in the adolescent's environment. The BMI reduction during the first 18 months
      postoperatively was paralleled by reduction in hedonic hunger; increases in
      hedonic hunger also paralleled the modest BMI increase at 24 months. In growth
      analysis, significant power gains are available to models using 4 or more points
      of data. However, only large effect sizes that are>.85 were detectable with a
      sample of 16 patients. CONCLUSION: These data provide preliminary evidence that
      hedonic hunger is in need of further study in adolescent patients receiving RYGB
      both preoperatively and postoperatively.

PMID- 24135562
TI  - Biotransformation of 17alpha-ethynyl substituted steroidal drugs with microbial
      and plant cell cultures: a review.
AB  - Structural modification of steroids through whole-cell biocatalysis is an
      invaluable procedure for the production of active pharmaceutical ingredients
      (APIs) and key intermediates. Modifications could be carried out with regio- and
      stereospecificity at positions hardly available for chemical agents. Much
      attention has been focused recently on the biotransformation of 17alpha-ethynyl
      substituted steroidal drugs using fungi, bacteria and plant cell cultures in
      order to obtained novel biologically active compounds with diverse structure
      features. Present article includes studies on biotransformation on 17alpha
      ethynyl substituted steroidal drugs using microorganisms and plant cell cultures.
      Various experimental and structural elucidation methods used in
      biotransformational processes are also highlighted. 

PMID- 24135563
TI  - Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination
      with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.
AB  - Polyanionic carbosilane dendrimers represent opportunities to develop new anti
      HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different
      stages of HIV replication have been proposed as compounds to decrease new HIV
      infections. Thus, we determined the potential use of our G2-STE16 carbosilane
      dendrimer in combination with other carbosilane dendrimers and ARVs for the use
      as topical microbicide against HIV-1. We showed that these combinations obtained
      100% inhibition and displayed a synergistic profile against different HIV-1
      isolates in our model of TZM.bl cells. Our results also showed their potent
      activity in the presence of an acidic vaginal or seminal fluid environment and
      did not activate an inflammatory response. This study is the first step toward
      exploring the use of different anionic carbosilane dendrimers in combination and
      toward making a safe microbicide. Therefore, our results support further studies
      on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1
      microbicide. FROM THE CLINICAL EDITOR: This paper describes the first steps
      toward the use of anionic carbosilane dendrimers in combination with antivirals
      to address HIV-1, paving the way to further studies on dendrimer/dendrimer or
      dendrimer/ARV combinations as topical anti-HIV-1 microbicides.

PMID- 24135564
TI  - Nanotherapeutic approaches for brain cancer management.
AB  - Around the world, cancer remains one of the most important causes of morbidity
      and mortality. Worldwide, approximately 238,000 new cases of brain and other
      central nervous system tumors are diagnosed every year. Nanotherapeutic
      approaches hold tremendous potential for diagnosis and treatment of brain cancer,
      including the ability to target complex molecular cargoes to the tumor sites and
      the capacity of crossing the blood-brain barrier and accessing to the brain after
      systemic administration. A new generation of "smart" nanoparticles has been
      designed as novel targeted delivery devices for new therapies including gene
      therapy, anti-angiogenic and thermotherapy. This review highlights the latest
      research, opportunities and challenges for developing novel nanotherapeutics for
      treating brain cancers. FROM THE CLINICAL EDITOR: This comprehensive review
      highlights the latest research results, opportunities and challenges for
      developing novel nanotherapeutics for treating brain cancers, with a special
      focus on "smart" nanoparticles as novel targeted delivery devices for new
      therapies including gene therapy, anti-angiogenic therapy and localized
      thermotherapy.

PMID- 24135565
TI  - Biogas production from co-digestion of corn stover and chicken manure under
      anaerobic wet, hemi-solid, and solid state conditions.
AB  - Corn stover (CS) and chicken manure (CM) are ubiquitous agricultural wastes at
      low cost and have the potential to achieve a nutrient-balance when mixed together
      to produce biomethane via anaerobic digestion (AD). The main objective of this
      work was to investigate methane production at different CS to CM ratios and to
      evaluate the process stability under wet (W-AD), hemi-solid state (HSS-AD) and
      solid state (SS-AD) conditions. Results showed that synergistic effects were
      found when mixing two substrates at CS:CM ratios of 3:1 and 1:1 (on volatile
      solid basis). The highest methane yield of 218.8 mL/g VS added was achieved in W
      AD at CS:CM ratio of 3:1. In SS-AD, the highest volumetric methane productivity
      of 14.2L methane/L reactor volume was found at CS:CM of 1:1. The results of this
      work provide useful information to improve the efficiency and stability of co
      digestion of CS and CM under different AD conditions.

PMID- 24135566
TI  - The potential for biomethane from grass and slurry to satisfy renewable energy
      targets.
AB  - A biomethane potential (BMP) assessment of grass silage yielded 107 m(3)CH4 t(
      1). Long term mono-digestion of grass silage can suffer due to a deficiency in
      essential nutrients; this may be overcome by co-digesting with slurry. Mono
      digestion of slurry achieved a low yield of 16 m(3)CH4 t(-1). BMP assessments at
      a range of co-digestion ratios indicated methane yields were between 4% and 11%
      lower than the values calculated from mono-digestion. This paper suggests that co
      digestion of the majority of slurry produced from dairy cows in Ireland with
      grass silage quantities equivalent to 1.1% of grassland on a 50:50 volatile
      solids basis would generate over 10% renewable energy supply in transport (RES
      T). The industry proposed would equate to 170 digesters each treating 10,000 t a(
      1) of grass silage and 40,000 t a(-1) of slurry from dairy cows.

PMID- 24135567
TI  - Phenotypic spectrum of Parachlorella kessleri (Chlorophyta) mutants produced by
      heavy-ion irradiation.
AB  - Heavy-ion mutagenesis is a technology used for effective production of genetic
      mutants. This study demonstrates that algal breeding using a unicellular alga,
      Parachlorella kessleri, by heavy-ion mutagenesis can improve lipid yield in
      laboratory experiments. The primary screening yielded 23 mutants among which a
      secondary screening yielded 7 strains, which were subjected to phenotypic assays.
      P. kessleri strains produced by heavy-ion radiation spanned a broad spectrum of
      phenotypes that differed in lipid content and fatty acid profiles. Starch grain
      morphology was distinctively altered in one of the mutants. The growth of strain
      PK4 was comparable to that of the wild type under stress-free culture conditions,
      and the mutant also produced large quantities of lipids, a combination of traits
      that may be of commercial interest. Thus, heavy-ion irradiation is an effective
      mutagenic agent for microalgae and may have potential in the production of
      strains with gain-of-function phenotypes. 

PMID- 24135568
TI  - Engineering bacteria for bioremediation of persistent organochlorine pesticide
      lindane (gamma-hexachlorocyclohexane).
AB  - Strategies were designed for bioremediation of the highly persistent toxic
      pesticide gamma-hexachlorocyclohexane (gamma-HCH) or lindane from the
      environment. Lindane caused the loss of stress-protective chaperone GroEL, and
      inhibited photosynthesis, respiration and nitrogen-fixation in Anabaena,
      resulting in growth arrest. To alleviate lindane toxicity, the linA2 gene,
      encoding HCH dehydrochlorinase from Sphingomonas paucimobilis B90, was knocked-in
      at an innocuous locus in Anabaena genome and over-expressed from an eco-friendly
      light-inducible PpsbA1 promoter. The recombinant Anabaena degraded >98% of 10 ppm
      lindane within 6-10 days. A LinA2 overexpressing Escherichia coli strain could
      degrade 10 ppm of all the isomers of lindane within 1h and displayed a visual
      degradation zone on a newly designed histochemical plate containing 50mg lindane
      within 12h. The study demonstrates (a) bioremediation of traces of lindane
      prevalent in paddy fields, using bioengineered photoautotrophic Anabaena, and,
      (b) biodegradation of huge stockpiles of lindane, by employing recombinant
      live/dead E. coli.

PMID- 24135570
TI  - Brain electrophysiological activity correlates with temporal processing in rats.
AB  - In this study, we present electroencephalographic (EEG) recording data obtained
      in correlation with timing behavior in rats trained in a 30-s peak interval (PI)
      procedure. The distribution of lever press responses was found to be Gaussian,
      peaking at approximately 30s: lever pressing behavior increased for 30s then
      decreased after the reinforcement time. We recorded EEG activity in the
      hippocampus (hippocampal theta wave) and striatum during the task, and evaluated
      whether the EEG power correlated with the behavior pattern. We found that the
      striatum EEG, but not the hippocampal theta wave, showed a good correlation with
      the response pattern in the 30-s PI. This result suggests that striatum neurons
      fired more synchronously at the time of reinforcement, thus supporting a critical
      role for synchronization of firing of striatal neurons in regulating timing
      mechanisms. This article is part of a Special Issue entitled: Associative and
      Temporal Learning. 

PMID- 24135569
TI  - Dissociations between interval timing and intertemporal choice following
      administration of fluoxetine, cocaine, or methamphetamine.
AB  - The goal of our study was to characterize the relationship between intertemporal
      choice and interval timing, including determining how drugs that modulate brain
      serotonin and dopamine levels influence these two processes. In Experiment 1,
      rats were tested on a standard 40-s peak-interval procedure following
      administration of fluoxetine (3, 5, or 8 mg/kg) or vehicle to assess basic
      effects on interval timing. In Experiment 2, rats were tested in a novel
      behavioral paradigm intended to simultaneously examine interval timing and
      impulsivity. Rats performed a variant of the bi-peak procedure using 10-s and 40
      s target durations with an additional "defection" lever that provided the
      possibility of a small, immediate reward. Timing functions remained relatively
      intact, and 'patience' across subjects correlated with peak times, indicating a
      negative relationship between 'patience' and clock speed. We next examined the
      effects of fluoxetine (5 mg/kg), cocaine (15 mg/kg), or methamphetamine (1 mg/kg)
      on task performance. Fluoxetine reduced impulsivity as measured by defection time
      without corresponding changes in clock speed. In contrast, cocaine and
      methamphetamine both increased impulsivity and clock speed. Thus, variations in
      timing may mediate intertemporal choice via dopaminergic inputs. However, a
      separate, serotonergic system can affect intertemporal choice without affecting
      interval timing directly. This article is part of a Special Issue entitled:
      Associative and Temporal Learning.

PMID- 24135571
TI  - Current status of syphilis vaccine development: need, challenges, prospects.
AB  - Syphilis is a multistage disease caused by the invasive spirochete Treponema
      pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy,
      syphilis remains a prevalent disease in developing countries and has re-emerged
      as a public health threat in developed nations. In addition to the medical burden
      imparted by infectious syphilis, congenital syphilis is considered the most
      significant infectious disease affecting fetuses and newborns worldwide, and
      individuals afflicted with syphilis have an enhanced risk for HIV transmission
      and acquisition. The global disease burden of syphilis and failure of decades of
      public health efforts to stem the incidence of disease highlight the need for an
      effective syphilis vaccine. Although challenges associated with T. pallidum
      research have impeded understanding of this pathogen, the existence of a relevant
      animal model has enabled insight into the correlates of disease protection.
      Complete protection against infection has been achieved in the animal model using
      an extended immunization regimen of gamma-irradiated T. pallidum, demonstrating
      the importance of treponemal surface components in generation of protective
      immunity and the feasibility of syphilis vaccine development. Syphilis is a prime
      candidate for development of a successful vaccine due to the (1) research
      community's accumulated knowledge of immune correlates of protection; (2)
      existence of a relevant animal model that enables effective pre-clinical
      analyses; (3) universal penicillin susceptibility of T. pallidum which enhances
      the attractiveness of clinical vaccine trials; and (4) significant public health
      benefit a vaccine would have on reduction of infectious/congenital syphilis and
      HIV rates. Critical personnel, research and market gaps need to be addressed
      before the goal of a syphilis vaccine can be realized, including recruitment of
      additional researchers to the T. pallidum research field with a proportional
      increase in research funding, attainment of a definitive understanding of
      correlates of protection in humans, and engagement of industry/funding
      partnerships for syphilis vaccine production. 

PMID- 24135573
TI  - Safety and immunogenicity of a tetravalent dengue vaccine in healthy children
      aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.
AB  - BACKGROUND: Dengue disease is a major public health problem across the Asia
      Pacific region for which there is no licensed vaccine or treatment. We evaluated
      the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV)
      in children in Malaysia. METHODS: In this observer-blind, placebo-controlled,
      Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD
      TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of
      reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs)
      reported throughout the study, and immunogenicity expressed as geometric mean
      titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody
      titres. RESULTS: 250 participants enrolled in the study (CYD-TDV: n=199; placebo:
      n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with
      placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and
      slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in
      frequency with each subsequent dose and were similar overall between groups (CYD
      TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were
      transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV
      and placebo groups, respectively. No deaths were reported. Baseline
      seropositivity against each of the four DENV serotypes was similar between
      groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs
      increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8
      (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and
      DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold
      (DENV-1) to 7.96-fold (DENV-3). CONCLUSIONS: This study demonstrated a
      satisfactory safety profile and a balanced humoral immune response against all
      four DENV serotypes for CYD-TDV administered via a three-dose regimen to children
      in Malaysia.

PMID- 24135574
TI  - The economic burden of sixteen measles outbreaks on United States public health
      departments in 2011.
AB  - BACKGROUND: Despite vaccination efforts and documentation of elimination of
      indigenous measles in 2000, the United States (US) experienced a marked increase
      in imported cases and outbreaks of measles in 2011. Due to the high
      infectiousness and potential severity of measles, these outbreaks require a
      vigorous response from public health institutions. The effort and resources
      required to respond to these outbreaks are likely to impose a significant
      economic burden on these institutions. OBJECTIVE: To estimate the economic burden
      of measles outbreaks (defined as >= 3 epidemiologically linked cases) on the
      local and state public health institutions in the US in 2011. METHODS: From the
      perspective of local and state public health institutions, we estimated personnel
      time and resources allocated to measles outbreak response in local and state
      public health departments, and estimated the corresponding costs associated with
      these outbreaks in the US in 2011. We used cost and resource utilization data
      from previous studies on measles outbreaks in the US and, relying on outbreak
      size classification based on a case-day index, we estimated costs incurred by
      local and state public health institutions. RESULTS: In 2011, the US experienced
      16 outbreaks with 107 confirmed cases. The average duration of an outbreak was 22
      days (range: 5-68). The total estimated number of identified contacts to measles
      cases ranged from 8936 to 17,450, requiring from 42,635 to 83,133 personnel
      hours. Overall, the total economic burden on local and state public health
      institutions that dealt with measles outbreaks during 2011 ranged from an
      estimated $2.7 million to $5.3 million US dollars. CONCLUSION: Investigating and
      responding to measles outbreaks imposes a significant economic burden on local
      and state health institutions. Such impact is compounded by the duration of the
      outbreak and the number of potentially susceptible contacts.

PMID- 24135572
TI  - Microbiome, sex hormones, and immune responses in the reproductive tract:
      challenges for vaccine development against sexually transmitted infections.
AB  - The female and male reproductive tracts are complex eco-systems where immune
      cells, hormones, and microorganisms interact. The characteristics of the
      reproductive tract mucosa are distinct from other mucosal sites. Reproductive
      tract mucosal immune responses are compartmentalized, unique, and affected by
      resident bacterial communities and sex hormones. The female and male genital
      microbiomes are complex environments that fluctuate in response to external and
      host-associated stimuli. The female vaginal microbiota play an important role in
      preventing colonization by pathogenic organisms. Sex hormones and their duration
      of exposure affect the composition and stability of the microbiome as well as
      systemic and mucosal immune responses. In addition to the characteristics of the
      pathogen they are targeting, successful vaccines against sexually transmitted
      pathogens must take into account the differences between the systemic and mucosal
      immune responses, the compartmentalization of the mucosal immune responses, the
      unique characteristics of the reproductive tract mucosa, the role of the mucosal
      bacterial communities, the impact of sex hormones, and the interactions among all
      of these factors. 

PMID- 24135575
TI  - Validation of the French national health insurance information system as a tool
      in vaccine safety assessment: application to febrile convulsions after pediatric
      measles/mumps/rubella immunization.
AB  - In the French national health insurance information system (SNIIR-AM), routine
      records of health claimed reimbursements are linked to hospital admissions for
      the whole French population. The main focus of this work is the usability of this
      system for vaccine safety assessment programme. Self-controlled case series
      analyses were performed using an exhaustive SNIIR-AM extraction of French
      children aged less than 3 years, to investigate the relationship between MMR
      immunization and children hospitalizations for febrile convulsions, a well
      documented rare adverse event, over 2009-2010. The results suggest a significant
      increase of febrile convulsions during the 6-11 days period following any MMR
      immunization (IRR=1.49, 95% CI=1.22, 1.83; p=0.0001) and no increase 15-35 days
      post any MMR immunization (IRR=1.03, 95% CI=0.89, 1.18; p=0.72). These results
      are in accordance with other results obtained from large epidemiologic studies,
      which suggest the usability of the SNIIR-AM as a relevant database to study the
      occurrence of adverse events associated with immunization. For future use,
      results associated with risk of convulsion during the day of vaccination should
      nevertheless be considered with particular caution. 

PMID- 24135576
TI  - Vaccination coverage levels among children enrolled in the Vaccine Safety
      Datalink.
AB  - INTRODUCTION: The Vaccine Safety Datalink (VSD) is a collaborative project whose
      infrastructure provides comprehensive medical and immunization histories for more
      than 9 million adults and children annually, a predominantly insured population.
      This study provides the coverage rates of recommended vaccines among children 19
      35 months in the VSD from 2005 through 2010. We examine the consistency in
      vaccine coverage levels, detect possible trends, and evaluate any effect of
      vaccine shortages on coverage in the VSD. METHODS: We included data from all 10
      VSD sites, and examined each year independently. Coverage rates were defined as
      the percentage of children in the VSD aged 19, 24, or 35 months in a given study
      year who had received the specified Advisory Committee on Immunization Practices
      (ACIP) recommended vaccine(s). RESULTS: We assessed coverage on 658,154 children.
      The overall coverage rate for children receiving all of the specified ACIP
      recommended vaccines was 73%, 80%, and 78% at ages 19, 24, and 35 months
      respectively. The range of coverage across all ages and years was 95-97% for
      polio vaccine, 91-97%, for MMR vaccine, 94-97% for HepB vaccine, 81-95% for DTaP
      vaccine, 90-95% for varicella vaccine, 66-91% for PCV, and 93-98% for Hib
      vaccine. Coverage rates of 4 or more doses of PCV were relatively low in 2005
      possibly due to a vaccine shortage, and increased sharply in 2007. Hib vaccine
      coverage was relatively stable among all ages until 2009 when rates declined
      among children aged 19 and 24 months also during a vaccine shortage. CONCLUSIONS:
      Vaccine coverage in the VSD is high, but there is a decline from 2005 to 2010.
      The results of this study provide benchmark data for future studies, and describe
      how vaccine supply shortages and resulting changes in ACIP recommendations may
      have affected vaccine coverage rates in the VSD.

PMID- 24135578
TI  - Failures, mistakes and shortcomings of my stroke trials.

PMID- 24135577
TI  - Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide
      based therapeutic vaccine.
AB  - A vaccine adjuvant that can effectively promote cell-mediated immunity is
      currently not available. Because of the ability of a Candida skin test reagent
      injection to induce common wart regression, our group is using it as a novel
      adjuvant in a clinical trial of a peptide-based human papillomavirus therapeutic
      vaccine. The goal of this current study was to investigate the mechanisms of how
      Candida enhances the vaccine immune responses. Maturation effects on Langerhans
      cells, capacity to proliferate T-cells, expression of cytokines and pattern
      recognition receptors by Langerhans cells, and ability to induce Th1, Th2, and
      Th17 responses were investigated in healthy subjects. The vaccine, human
      papillomavirus peptides with Candida, demonstrated partial maturation effects on
      Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and
      CD80 (p<0.00001) levels, and showed T-cell proliferative capacity (p<0.00001)
      when presented by Langerhans cells in vitro. Interestingly, the maturation
      effects were due to the peptides while Candida was responsible for the T-cell
      proliferation. The cytokine profile (IL-1beta, IL-6, IL-8, IL-10, IL-12p40, IL
      23Ap19, IFN-gamma and TNF-alpha) of Langerhans cells treated with the vaccine or
      Candida alone showed that IL-12p40 mRNA was most frequently induced, and IL-12p70
      protein was detected in the supernatants. The presence of pattern recognition
      receptors known to associate with Candida albicans (DC-SIGN, dectin-1, dectin-2,
      galectin-3, mincle, mannose receptor, Toll-like receptors-1, 2, 4, 6 and 9) were
      demonstrated in all subjects. On the other hand, the induction of Th1 response
      demonstrated by IFN-gamma secretion by CD4 cells stimulated with the vaccine or
      Candida pulsed Langerhans cells was demonstrated only in one subject. In summary,
      the Langerhans cell maturation effects of the vaccine were due to the peptides
      while the T-cell proliferative capacity was derived from Candida, and the most
      frequently induced cytokine was IL-12. 

PMID- 24135579
TI  - Perioperative management of patients with mastocytosis.

PMID- 24135580
TI  - Epinephrine for cardiac arrest: are we doing more harm than good?

PMID- 24135582
TI  - Avatar of the universal definition of periprocedural myocardial infarction.

PMID- 24135583
TI  - Potential risk factors associated with contact dermatitis, lameness, negative
      emotional state, and fear of humans in broiler chicken flocks.
AB  - The objectives of this study were to 1) identify determinants of poor welfare in
      commercial broiler chicken flocks by studying the associations between selected
      resource-based measures (RBM, potential risk factors), such as litter quality and
      dark period, and animal-based welfare indicators (ABM), such as foot pad
      dermatitis and lameness, and 2) establish the breadth of effect of a risk factor
      by determining the range of animal welfare indicators associated with each of the
      risk factors (i.e., the number of ABM related to a specific RBM). Eighty-nine
      broiler flocks were inspected in 4 European countries (France, Italy, the United
      Kingdom, and the Netherlands) in a cross-sectional study. The ABM were contact
      dermatitis (measured using scores of foot-pad dermatitis and hock burn,
      respectively), lameness (measured as gait score), fear of humans (measured by the
      avoidance distance test and the touch test), and negative emotional state
      (measured using qualitative behavior assessment, QBA). In a first step, risk
      factors were identified by building a multiple linear regression model for each
      ABM. Litter quality was identified as a risk factor for contact dermatitis.
      Length of dark period at 3 wk old (DARK3) was a risk factor for the touch test
      result. DARK3 and flock age were risk factors for lameness, and the number of
      different stockmen and DARK3 were risk factors for QBA results. Next, the ABM
      were grouped according to risk factor and counted. Then, in a second step,
      associations between the ABM were investigated using common factor analysis. The
      breadth of a risk factor's effect was judged by combining the number (count) of
      ABM related to this factor and the strength of association between these ABM.
      Flock age and DARK3 appeared to affect several weakly correlated ABM, thus
      indicating a broad range of effects. Our findings suggest that manipulation of
      the predominant risk factors identified in this study (DARK3, litter quality, and
      slaughter age) could generate improvements in the related ABM and thereby enhance
      the birds' overall welfare status. 

PMID- 24135581
TI  - Consideration of a new definition of clinically relevant myocardial infarction
      after coronary revascularization: an expert consensus document from the Society
      for Cardiovascular Angiography and Interventions (SCAI).
AB  - Numerous definitions have been proposed for the diagnosis of myocardial
      infarction (MI) after coronary revascularization. The universal definition for MI
      designates post procedural biomarker thresholds for defining percutaneous
      coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass
      grafting (CABG)-related MI (type 5), which are of uncertain prognostic
      importance. In addition, for both the MI types, cTn is recommended as the
      biomarker of choice, the prognostic significance of which is less well validated
      than CK-MB. Widespread adoption of a MI definition not clearly linked to
      subsequent adverse events such as mortality or heart failure may have serious
      consequences for the appropriate assessment of devices and therapies, may affect
      clinical care pathways, and may result in misinterpretation of physician
      competence. Rather than using an MI definition sensitive for small degrees of
      myonecrosis (the occurrence of which, based on contemporary large-scale studies,
      are unlikely to have important clinical consequences), it is instead recommended
      that a threshold level of biomarker elevation which has been strongly linked to
      subsequent adverse events in clinical studies be used to define a "clinically
      relevant MI." The present document introduces a new definition for "clinically
      relevant MI" after coronary revascularization (PCI or CABG), which is applicable
      for use in clinical trials, patient care, and quality outcomes assessment. 

PMID- 24135584
TI  - Aerial dust concentration in cage-housed, floor-housed, and aviary facilities for
      laying hens.
AB  - Agricultural workers, and pig and poultry farmers in particular, are exposed to
      airborne contaminants including organic dusts, gases, fungi, bacteria, and
      endotoxins that can have adverse effects on their respiratory health. To date,
      data comparing the aerial dust concentrations in the different hen-housing
      systems used by commercial poultry farmers are scarce. An epidemiological study
      was conducted in commercial housing facilities for laying hens, half of which
      were housed in a cage system without litter and the remaining half on an on-floor
      system with litter. The aims were to measure and compare the ambient dust
      concentrations in the different housing systems and identify any factors in
      building design and hen management that could influence the dust burden. An
      average concentration of respirable ambient dusts (<=4 MUm) of 0.37 mg/m(3) (95%
      CI [0.31-0.42]) was measured in the on-floor system, and this value was higher
      than average values in the cage system {0.13 mg/m(3) (95% CI [0.11-0.14]) P =
      0.01}. The highest dust concentration was observed in aviaries (1.19 mg/m(3)
      [0.80-1.59]). The type of housing and the presence of litter therefore had a
      preponderant effect on air quality. Dust concentrations in caged buildings were
      influenced by cage design and rearing practices, whereas litter management, the
      age of hens, and temperature control were determining factors for dust levels in
      on-floor houses. This study underlines the need for information and preventive
      measures to reduce the exposure of poultry workers to bioaerosols, particularly
      in alternative systems where high levels of ambient dust were observed. 

PMID- 24135585
TI  - The effectiveness of peppermint and thyme essential oil mist in reducing
      bacterial contamination in broiler houses.
AB  - The antimicrobial properties of essential oils have been demonstrated by various
      in vitro studies, whereas their effect on poultry farm hygiene has not been
      thoroughly investigated, in particular with reference to aerial treatment. The
      present study aims to assess the antibacterial effects of natural essential oils
      in broiler houses. Two experimental rooms were fogged with aqueous solutions of
      peppermint and thyme oils. The control room was sprayed with pure water. The
      experiment was conducted on broilers aged 1 to 42 d. The rooms were fogged every
      3 d. One day after fogging, the total counts of mesophilic aerobic bacteria,
      Enterobacteriaceae, and mannitol-positive staphylococci were determined. Samples
      were collected from the air, litter, walls, and drinkers. The results of the
      study demonstrate that essential oil mist may improve hygiene standards in
      broiler farms. During broiler growth, the mean total counts of mesophilic
      bacteria in the rooms treated with essential oils were lower (P < 0.01 or P <
      0.05) in comparison with the control. Enterobacteriaceae and staphylococci counts
      were also higher in the control group. A single exception was noted in a litter
      sample where the mean count of Enterobacteriaceae in the room fogged with
      peppermint oil was higher than in the control. Both oils reduced bacterial
      counts, but thyme oil was more effective in reducing coliform bacteria, whereas
      peppermint oil had a higher inhibitory effect on the proliferation of
      staphylococci. These promising results encourage further research to determine
      the optimal doses and the effects of essential oils and their combinations on the
      living conditions and health status of broiler chickens. 

PMID- 24135586
TI  - Influence of monochromatic light on quality traits, nutritional, fatty acid, and
      amino acid profiles of broiler chicken meat.
AB  - The role of monochromatic lights was investigated on meat quality in 1-d-old
      straight-run broiler chicks (n = 360), divided into 6 light sources with 6
      replicates having 10 chicks in each replicate. Six light sources were described
      as incandescent bulbs (IBL, as a control) and light-emitting diode (LED) light
      colors as white light (WL), blue light, red light (RL), green light, and yellow
      light. Among LED groups, the RL increased the concentration of monounsaturated
      fatty acids (P < 0.001), saturated fatty acids (P < 0.001), and the
      saturated:polyunsaturated fatty acid ratio (P < 0.001), but reduced the
      concentration of polyunsaturated fatty acid, n-3 fatty acid, and n-6 fatty acid.
      The IBL increased the n-3 and sulfur-containing amino acids but reduced the n-6:n
      3 nonessential amino acids. The WL improved the concentration of most of the
      essential amino acids (P < 0.01) and nonessential amino acids (P < 0.01) of
      breast meat. It can be extracted that the light produced by LED responded similar
      to the IBL light in influencing nutrient contents of meat. Moreover, LED is not
      decisive in improving fatty acid composition of meat. However, the role of IBL in
      reducing n-6:n-3 ratio and enhancing n-3 cannot be neglected. Among LED, WL is
      helpful in improving essential and nonessential amino acid contents of broiler
      meat. 

PMID- 24135587
TI  - Effects of perch access and age on physiological measures of stress in caged
      White Leghorn pullets.
AB  - The neuroendocrine system controls animals' adaptability to their environments by
      releasing psychotropic compounds such as catecholamines [epinephrine (EP),
      norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5
      hydroxytryptamine or 5-HT). Changes of these neuroendocrine compounds have been
      used as biomarkers of animals' stress responses associated with their well-being.
      Assuming that pullets, like laying hens, are highly motivated to perch, we
      hypothesize that pullets with access to perches will experience less stress than
      pullets that never have access to perches. The objective of this study was to
      examine the effects of perch access and age on physiological measurements of
      stress in White Leghorn pullets housed in conventional cages. Hatchlings (n =
      1,064) were randomly assigned to 28 cages. Two parallel metal round perches were
      installed in each of 14 cages assigned the perch treatment, whereas control cages
      were without perches. Two birds per cage were bled at wk 4, 6, and 12 wk of age.
      Plasma levels of CORT, DA, EP, and NE, blood concentrations of 5-HT and Trp, and
      heterophil to lymphocyte ratios were measured. Data were analyzed using a 2-way
      ANOVA. The perch treatment or its interaction with age did not affect any
      parameter measured in the study. The increase in the concentrations of
      circulating EP, NE, 5-HT (numerical increase at 4 wk), and Trp in 4- and 6-wk-old
      pullets compared with 12-wk-old pullets is unclear, but may have been due to
      acute handling stress at younger ages. In contrast, concentrations of DA were
      less at 4 wk compared with levels at 6 and 12 wk of age. Plasma CORT levels and
      the heterophil to lymphocyte ratio, indicators of long-term stress, were
      unaffected by age (P = 0.07 and 0.49, respectively). These results indicated that
      age, but not perch access, affects neuroendocrine homeostasis in White Leghorn
      pullets. Pullets that were never exposed to perches showed no evidence of
      eliciting a stress response. 

PMID- 24135588
TI  - Genetic characterization and conservation priorities of chicken lines.
AB  - Molecular markers are a useful tool for evaluating genetic diversity of chicken
      genetic resources. Seven chicken lines derived from the Plymouth Rock breed were
      genotyped using 40 microsatellite markers to quantify genetic differentiation and
      assess conservation priorities for the lines. Genetic differentiation between
      pairs of the lines (pairwise FST) ranged from 0.201 to 0.422. A neighbor-joining
      tree of individuals, based on the proportion of shared alleles, formed clearly
      defined clusters corresponding to the origins of the lines. In Bayesian model
      based clustering, most individuals were clearly assigned to single clusters
      according to line origin and showed no admixture. These results indicated that a
      substantial degree of genetic differentiation exists among the lines. To decide
      priorities for conservation, the contribution of each line to the genetic
      diversity was estimated. The result indicated that a loss of 4 of the 7 lines
      would lead to a loss from 1.14 to 3.44% of total genetic diversity. The most
      preferred line for conservation purposes was identified based on multilocus
      microsatellite analysis. Our results confirmed that characterization by means of
      molecular markers is helpful for establishing a plan for conservation of chicken
      genetic resources. 

PMID- 24135589
TI  - Effects of different CpG oligodeoxynucleotides with inactivated avian H5N1
      influenza virus on mucosal immunity of chickens.
AB  - Oligodeoxynucleotide containing unmethylated CpG motifs (CpG-ODN) has been proved
      to be a potent and safe vaccine adjuvant. However, the application of CpG-ODN in
      poultry vaccines was limited because of its high cost to benefit ratio. The
      objective of this study was to identify the CpG-ODN with efficient adjuvant
      activity and low cost in chickens. Four sequences of CpG-ODN were designed based
      on CpG-ODN 2006, which was used as a template and positive sequence in our study.
      In the current study, in vitro observations revealed that the designed CpG-ODN
      had efficient immunostimulatory effects on chicken splenic lymphocytes. The in
      vivo results showed that the mRNA expressions of IL-6, IL-12, interferon-gamma,
      and Toll-like receptor (TLR) 21 in upper respiratory tract tissues increased
      significantly in the early period after intranasal immunization with inactivated
      avian H5N1 influenza virus (IAIV) and CpG-ODN (P < 0.01). In addition, the avian
      influenza virus (AIV)-specific secretory IgA antibody level in the lavage fluid
      of upper respiratory tract increased significantly after intranasal immunization
      with IAIV and CpG-ODN, so did AIV-specific IgG in serum (P < 0.01). Among all the
      designed CpG-ODN, CpG-ODN F3 with an addition of poly-guanosine strings at the 3'
      end not only had the best enhancement on local mucosal immune response but also
      showed an effective induction of systemic immune response. Most importantly, the
      virus challenge study showed that prior administration of IAIV with CpG-ODN F3
      could protect chickens effectively against live AIV H5N1 challenge. Additionally,
      among all the CpG-ODN in our study, the cost of the designed CpG-ODN F3 was the
      lowest because of the partially phosphorothioate backbone. Therefore, we
      speculated that CpG-ODN F3 with efficient adjuvant activity and a big cost
      advantage over CpG-ODN F1 (CpG-ODN 2006) might serve as an efficient and
      affordable nasal adjuvant for inactivated AIV vaccine in chicken. 

PMID- 24135590
TI  - Molecular survey of enteric viruses in commercial chicken farms in Korea with a
      history of enteritis.
AB  - Several enteric viruses have increasingly received attention as potential
      causative agents of runting-stunting syndrome (RSS) in chickens. A molecular
      survey was performed to determine the presence of a broad range of enteric
      viruses, namely chicken astrovirus (CAstV), avian nephritis virus (ANV), chicken
      parvovirus (ChPV), infectious bronchitis virus (IBV), avian rotavirus (AvRV),
      avian reovirus (ARV), and fowl adenovirus (FAdV), in intestinal samples derived
      from 34 commercial chicken flocks that experienced enteritis outbreaks between
      2010 and 2012. Using techniques such as PCR and reverse-transcription PCR,
      enteric viruses were identified in a total of 85.3% of investigated commercial
      chicken flocks in Korea. Furthermore, diverse combinations of 2 or more enteric
      viruses were simultaneously identified in 51.7% of chicken farms positive for
      enteric viruses. The rank order of positivity for enteric viruses was as follows:
      ANV (44.1%), CAstV (38.2%), ChPV (26.5%), IBV (20.6%), ARV (8.8%), AvRV (5.9%),
      and FAdV (2.9%). Additionally, other pathogens such as Escherichia coli,
      Salmonella spp., Eimeria spp., and FAdV were detected in 79% of chicken flocks
      positive for enteric viruses using PCR, bacterial isolation, and microscopic
      examination. The results of our study indicate the presence of several enteric
      viruses with various combinations in commercial chicken farms that experienced
      enteritis outbreaks. Experimental studies are required to further understand the
      roles of enteric viruses in RSS in commercial chickens. 

PMID- 24135591
TI  - Genetic analysis of duck circovirus in Pekin ducks from South Korea.
AB  - The genetic organization of the 24 duck circovirus (DuCV) strains detected in
      commercial Pekin ducks from South Korea between 2011 and 2012 is described in
      this study. Multiple sequence alignment and phylogenetic analyses were performed
      on the 24 viral genome sequences as well as on 45 genome sequences available from
      the GenBank database. Phylogenetic analyses based on the genomic and open reading
      frame 2/cap sequences demonstrated that all DuCV strains belonged to genotype 1
      and were designated in a subcluster under genotype 1. Analysis of the capsid
      protein amino acid sequences of the 24 Korean DuCV strains showed 10
      substitutions compared with that of other genotype 1 strains. Our analysis showed
      that genotype 1 is predominant and circulating in South Korea. These present
      results serve as incentive to add more data to the DuCV database and provide
      insight to conduct further intensive study on the geographic relationships among
      these virus strains. 

PMID- 24135592
TI  - The comprehensive diagnosis and prevention of duck plague in northwest Shandong
      province of China.
AB  - Here, we report the first outbreak of duck plague (DP) confirmed in 4 tissue
      samples that were collected since August 2012 from the northwestern region of
      Shandong province, China. Among these, 3 were collected from commercial Jin-ding
      variety layer ducks and one from Cherry Valley meat-breeding ducks. The sick
      ducks (7 to 49 wk old) were characterized by typical DP symptoms and necroscopic
      features. The flocks experienced high morbidity and mortality rates, and
      decreased production performance, which led to tremendous economic losses. The
      diagnosis of DP infection was confirmed by comprehensive analyses of
      epidemiological data, clinical signs, necroscopic features, histopathological
      examinations, and viral isolation and identification. According to the laws of
      the People's Republic of China on Animal Epidemic Prevention, emergency measures
      were implemented to control the outbreak, which included slaughter of the
      infected flocks and proper disposal of the bodies, manure, and other wastes,
      disinfection and thorough cleaning of the duck facilities, fields, tools,
      utensils, and devices, as well as emergency vaccination of the threatened flocks
      and the implementations of revised immunization procedures. Possible causes of
      the DP outbreak and the prevalence of the virus in Shandong province were also
      analyzed and are discussed herein.

PMID- 24135593
TI  - Temporary modulation of responses to common vaccines and serum cation status in
      broilers during exposure to low doses of aflatoxin B1.
AB  - The purpose of this study was to observe the effects of low doses of aflatoxin B1
      (AFB1) on responses to common vaccines and levels of serum cations in broilers.
      Male broilers at 7 d of age were fed control (no AFB1), a 75 ug of AFB1/kg (75
      ppb of AFB1) diet, or a 750 ug of AFB1/kg (750 ppb of AFB1) diet. The 750 ppb of
      AFB1 diet resulted in a temporary increase in ELISA titers against Newcastle
      disease virus (P = 0.014) and infectious bursal disease virus (P = 0.005) during
      wk 2 and 4 of exposure, respectively, compared with the control diet. Conversely,
      lower (P <= 0.01) serum protein concentrations were found in broilers under the
      750 ppb AFB1 diet during wk 2 and 4. During wk 2 of exposure, lower serum levels
      of potassium were noted in birds under both the 75 (P = 0.037) and 750 ppb (P =
      0.000) AFB1 diets compared with those under the control diet. During wk 5, higher
      serum magnesium (P = 0.004), and sodium (P = 0.000) under the 750 ppb AFB1 diet
      were found compared with the control diet. These data indicate that low dietary
      levels of AFB1 can temporarily increase or decrease the studied serological
      variables in broilers depending upon the stage of exposure. 

PMID- 24135594
TI  - Transgenerational epigenetic effects on innate immunity in broilers: an
      underestimated field to be explored?
AB  - Transgenerational epigenetics is becoming more and more important for
      understanding the variation of physiological responses of individuals to the
      environment and the inheritance of these responses based on all mechanisms other
      than the actual DNA nucleotide sequence. Transgenerational epigenetics is the
      phenomenon that the information of the environment of (usually) a female animal
      is translated into memory-like responses preparing the offspring. As a
      consequence, individuals of the next generation may show different phenotypic
      traits depending whether their mothers were kept under different environmental
      conditions. This may result in either positive or negative effects on the next
      generation individuals, which is different from individuals from mothers that
      have been kept in a different environment. Transgenerational epigenetic effects
      have been proposed and indicated for specific immune (T cell and antibody)
      responses (especially in mammals, but also in birds) and innate immunity
      (nonvertebrates), but surprisingly very little is known of transgenerational
      effects on innate immunity in chickens. Given the short lifespan of the chicken
      and therefore the likely dependence of chicken on innate immune mechanisms, more
      attention should be given to this arm of immunity and mechanisms of inheritance
      including transgenerational effects that can be initiated in the breeder
      generation. In addition, it is becoming evident that innate immunity also
      underlies metabolic disorders in broilers. In the current paper, we will argue
      that although very little is known of transgenerational effects of innate
      immunity in poultry, more attention should be given to this type of study. We
      will illustrate examples of transgenerational epigenetics, and finally propose
      strategies that should reveal the presence of transgenerational epigenetic
      effects on innate immunity in chickens and strategies to modulate breeder birds
      such that these effects positively affect innate immunity of broilers. It is
      suggested that a mismatch between breeder environment and broiler environment may
      account for unwanted effects of innate immunity in the broiler. 

PMID- 24135595
TI  - Evaluation of soybean meal source and particle size on broiler performance,
      nutrient digestibility, and gizzard development.
AB  - Although there have been several reports concerning the effects of particle size
      of cereal grains on productive performance of poultry, there is limited
      information about the effects of soybean meal (SBM) particle size on broiler
      performance. The objective of the present experiments was to evaluate the effects
      of SBM source and particle size on broiler performance, gizzard weight, and
      nutrient digestibility. The first experiment was a 2 * 2 factorial arrangement of
      2 SBM sources: expeller-extracted (ESBM) and solvent-extracted (SSBM), and 2
      particle sizes: coarse grind, 971 um, and fine grind, 465 um. The second
      experiment was a 2 * 2 factorial arrangement of 2 ESBM particle sizes: coarse
      grind, 1,290 um, and fine grind, 470 um, and 2 corn particle sizes: coarse grind,
      1,330 um, and fine grind, 520 um. In the first experiment, there was an
      interaction (P < 0.05) between SBM source and particle size on BW at 49 d of age.
      No differences in BW were observed when birds were fed coarse SSBM or ESBM,
      whereas birds fed diets containing fine ESBM exhibited lower BW than birds fed
      diets containing fine SSBM. In the second experiment, fine-grind ESBM (P < 0.05)
      and corn (P < 0.01) produced greater 19-d BW than did coarse grind. A significant
      interaction (P < 0.01) between ingredient type and particle size revealed that
      chicks fed coarse particles of corn or ESBM exhibited higher protein
      digestibility compared with chicks fed only fine particles. Corn particle size
      had a greater effect on gizzard weight than ESBM particle size. Birds fed diets
      that contained coarse corn had larger gizzards than birds fed fine corn (P <
      0.01), but differences in gizzard weight were not observed when birds were fed
      coarse or fine ESBM. Particles greater than 1,300 um depressed BW but improved
      protein digestibility. 

PMID- 24135596
TI  - Phytase transgenic corn in nutrition of laying hens: residual phytase activity
      and phytate phosphorus content in the gastrointestinal tract.
AB  - The residual activities of transgenic corn-derived and 2 commercial microbial
      phytases (PA and PB) along the gastrointestinal tract (GIT) of laying hens were
      compared to evaluate their relative resistance to hydrolysis in the GIT when
      added to P-deficient diets. The treatments consisted of a negative control (NC)
      diet containing 0.10 nonphytate P and an NC diet supplemented with transgenic
      corn-derived phytase (TCDP), PA, and PB at 500 to 5,000 FTU/kg of diet,
      respectively. Seven diets were fed to Hy-Line Brown laying hens (n = 504; 8
      replicates of 9 hens per treatment) for 21 d. At the end of the experiment, the
      hens were killed and digesta samples from the crop, proventriculus and gizzard,
      jejunum, and ileum were collected and analyzed for residual phytase activities
      and phytate P content. Phytase activity in the transgenic corn was determined to
      be 8,980 FTU/kg of DM. The residual phytase activities along the GIT had
      increased (P < 0.01) with the addition of TCDP, PA, and PB to the NC diets. The
      TCDP had higher residual activity (P < 0.05) in the crop, proventriculus and
      gizzard, jejunum, and ileum as compared with the PA and PB activity. There was a
      decrease (P < 0.01) in the phytate P content of the digesta from all sources of
      phytase supplementation in the NC diets. Residual phytate P content decreased
      caudally along the GIT of hens. The results of this research indicate that
      phytase expressed in corn is as efficacious as the commercial microbial phytases
      (PA and PB) in P-deficient diets for the improvement of phytate P digestibility,
      which would eliminate the need for supplemental phytase and corn separately in
      laying hen diets. 

PMID- 24135597
TI  - Effects of long-term supplementation of laying hens with high concentrations of
      cholecalciferol on performance and egg quality.
AB  - There is current interest in increasing human vitamin D dietary intake without
      having to modify human eating habits. One method to increase human dietary
      vitamin D intake is to generate eggs with increased concentrations of vitamin D
      through high-concentration vitamin D feeding in the diets of laying hens.
      Although eggs can be produced with high concentrations of vitamin D, the
      consequences of these diets on hen performance and egg quality have not been
      validated. The objective of this research is to quantify the effects of high
      concentrations of cholecalciferol (D3) on laying hen performance and egg quality.
      Hy-Line W36 laying hens were placed on 1 of 5 experimental diets for 40 wk: 1)
      control (contained 2,200 IU of D3/kg of diet), 2) control + 7,500 IU of D3/kg of
      diet (9,700 IU of D3/kg of diet total), 3) control + 15,000 IU of D3/kg of diet
      (17,200 IU of D3/kg of diet total), 4) control + 22,500 IU of D3/kg of diet
      (24,700 IU of D3/kg of diet total), and 5) control + 100,000 IU of D3/kg of diet
      (102,200 IU of D3/kg of diet total). Egg production and hen mortality were
      monitored daily. Feed intake was determined weekly. Eggs were collected at
      predetermined points throughout the 40-wk period (19 to 58 wk of bird age) for
      assessment of egg weight, egg component weights, Haugh unit, yolk color score,
      specific gravity, egg mass, and feed efficiency. There were no consistent
      differences among the dietary treatments over the experimental period. Hens
      supplemented with up to 102,200 IU of D3/kg of diet resulted in no significant
      reductions in egg production, feed intake, feed efficiency, egg component
      weights, yolk color, Haugh units, and specific gravity in comparison with the
      control-fed hens (P > 0.05). These data suggest the addition of cholecalciferol
      to the diet of the laying hen at concentrations up to 102,200 IU of D3/kg of diet
      had no consistent negative effects on laying hen performance or egg quality. 

PMID- 24135598
TI  - Oxidative stability of the meat of broilers supplemented with rosemary leaves,
      rosehip fruits, chokeberry pomace, and entire nettle, and effects on performance
      and meat quality.
AB  - Prevention of lipid oxidation needs special attention because a high proportion
      of fatty acids in broiler meat are unsaturated. A feeding experiment was
      conducted to evaluate the antioxidant effect of dietary addition of rosemary,
      chokeberry pomace, rosehip, or nettle in comparison with vitamin E. Male Ross PM3
      broilers caged in groups of 6 (4 replicated cages per treatment) were fed a
      balanced diet supplemented with 25 g/kg of herbal additive, 200 IU of alpha
      tocopheryl acetate/kg, or without supplementation from d 7 to 35. Intake,
      performance, and with the help of excreta samples, apparent fiber digestibility,
      ME content, and metabolizability of nitrogen and energy were recorded per cage.
      Feed was analyzed for total phenols and tocopherols. In each bird (n = 24 per
      treatment), carcass weight and relative organ weights were recorded, and skin and
      liver color were assessed. Abdominal fat was analyzed for induction time (h) of
      lipid oxidation (Rancimat). Breast meat was analyzed for total tocopherol content
      (mg/kg) and development of TBA reactive substances (TBARS; MUg of MDA/kg) over 9
      d of storage. Data were subjected to ANOVA considering treatment and, where
      applicable, storage time. Rosemary supplementation reduced oxidation (TBARS d 9:
      201; induction time: 2.48) and elevated tocopherol content (5.72) of the meat
      compared with control (470, 1.87, and 3.53, respectively). Rosemary-treated birds
      had a slightly lower carcass weight and a reduced nitrogen and energy
      metabolizability. Rosehip addition numerically decreased TBARS (319) and enhanced
      carcass weight (1.71 kg) compared with rosemary-treated birds (1.54 kg). Only a
      trend in antioxidant activity could be ascribed to chokeberry pomace, although
      dietary phenolic content was highest. Nettle did not improve oxidative stability
      (TBARS: 506; induction time: 1.91), although tocopherol content was elevated
      (6.51). Nettle treatment strongly intensified skin yellowness (b* of 20.6)
      compared with the control treatment (10.8). Clearly, rosemary is the most
      suitable dietary antioxidant investigated in this study, yet chokeberry and
      rosehip also exhibited interesting properties. 

PMID- 24135599
TI  - Effects of a probiotic, Enterococcus faecium, on growth performance, intestinal
      morphology, immune response, and cecal microflora in broiler chickens challenged
      with Escherichia coli K88.
AB  - The effects of feeding dehydrated Enterococcus faecium on growth performance,
      immune response, and cecal microflora in broiler chickens challenged with
      Escherichia coli K88 were investigated. Two hundred eighty-eight 1-d-old birds
      were randomly assigned to 4 treatments: negative control birds (N-con) fed a
      basal diet and not challenged with E. coli K88; positive control birds (P-con)
      fed a basal diet and challenged with E. coli K88; birds fed a basal diet
      including dehydrated E. faecium (Ef) at 1 * 10(9) cfu/kg of feed and challenged
      with E. coli K88; and birds fed a basal diet including the antibiotic colistine
      sulfate (Anti) at 10 mg/kg of feed and challenged with E. coli K88. Birds fed E.
      faecium had greater (P < 0.05) BW on d 14, 21, and 28 and greater (P < 0.05)
      jejunal villus height on d 21 and 28 compared with birds on the other treatments.
      Jejunal crypt depth was decreased (P < 0.05) in birds fed either E. faecium or
      antibiotic compared with P-con treatment birds on d 10, 21, and 28. Birds fed E.
      faecium had a greater (P < 0.05) concentration of IL-4 in their jejunal mucosa
      than did those in the N-con treatment group on d 10, 14, and 21. Infected birds,
      with or without E. faecium feeding, had a higher (P < 0.05) tumor necrosis factor
      alpha and secreted IgA in their jejunal mucosa than did those in the N-con
      treatment group on d 10 and 14. Birds fed E. faecium had lower (P < 0.05)
      concentrations of E. coli on d 14 and 28, less (P < 0.05) Clostridium perfringens
      on d 28, greater Lactobacillus counts on d 14 and 21, and greater (P < 0.05)
      Bifidobacterium in their cecal contents on d 21 than did the P-con birds. These
      results suggest that E. faecium can promote growth performance, improve
      intestinal morphology, and beneficially manipulate the cecal microflora in
      broilers challenged with E. coli K88. 

PMID- 24135600
TI  - The effect of vitamin E on laying performance and egg quality in laying hens fed
      corn dried distillers grains with solubles.
AB  - The objective of the present study was to investigate the effect of vitamin E on
      laying performance, egg quality, egg fatty acid composition, antioxidant
      capacity, and several biochemical parameters of laying hens fed corn distillers
      dried grains with solubles (DDGS) during the laying period (40 to 63 wk of age).
      A total of 360 Hy-Line Variety Brown hens were randomly assigned to 6 groups,
      consisting of 6 replicates with 10 hens each. Hens were allocated to diets 1
      through 6 in a 3 * 2 factorial design. The dietary treatments included 3 levels
      of DDGS (0, 10, and 20%) and 2 levels of vitamin E (0 and 200 mg/kg). The results
      indicated that yolk color and eggshell thickness increased with increasing DDGS
      (P < 0.05). However, increasing DDGS to 20% in laying hen diets significantly
      reduced feed conversion (P < 0.05). Supplementation with 200 mg/kg of vitamin E
      significantly improved egg production and yolk percentage (P < 0.05). Increasing
      the dietary levels of vitamin E caused a decrease in cholesterol and an increase
      in the alpha-tocopherol concentration of the egg yolk and serum (P < 0.05). Diets
      supplemented with DDGS decreased the proportion of saturated fatty acids (P <
      0.05) and increased the proportion of unsaturated fatty acids in egg yolk (P <
      0.05). Supplementation with high levels of vitamin E decreased malondialdehyde
      and increased glutathione peroxidase and total superoxide dismutase
      concentrations of the egg yolk and serum (P < 0.05). In conclusion, our results
      showed that DDGS was successfully fed to laying hens at levels up to 10% without
      adverse effects on laying performance. Additionally, vitamin E supplementation
      improved egg production and egg quality and provided health benefits to laying
      hens. 

PMID- 24135601
TI  - Sex-related differences of morphometric, densitometric, and geometric parameters
      of tibia and tarsometatarsal bone in 14-month-old ostriches (Struthio camelus).
AB  - The aim of the current study was to investigate basic morphometric, geometric,
      and densitometric parameters of tibia and tarsometatarsus in 14-mo-old male and
      female ostriches, and interrelationships between these parameters. The study was
      conducted on 20 tibiae and 20 tarsometatarsal bones of the left pelvic limb
      derived from 20 healthy 14-mo-old ostriches (Struthio camelus): 10 males and 10
      females. The following parameters were determined using peripheral quantitative
      computed tomography: bone mineral content (BMC), volumetric bone mineral density
      (vBMD), cortical content (CRT_CNT), cortical density (CRT_DEN), trabecular
      content, trabecular density (TRAB_DEN), bone area (TOT_A), trabecular area
      (TRAB_A), cortical area (CRT_A), cortical thickness (CRT_THK_C), periosteal
      circumference (PERI_C), endocortical circumference (ENDO_C), and strength-strain
      index (SSI) in the metaphysis and diaphysis of the bones. Statistical evaluation
      of the obtained results was performed using Student's t-test, and the Pearson
      correlation coefficient between the investigated parameters was determined. The
      obtained results have shown significant differences in proximal metaphysis
      between males and females when evaluating such parameters as CRT_DEN, TOT_A,
      TRAB_A, PERI_C, SSI in tibia (P < 0.05), and BMC, vBMD, TRAB_DEN, CRT_CNT, TOT_A,
      TRAB_A, cortical area, PERI_C, ENDO_C, SSI in tarsometatarsus (P < 0.05).
      Significant differences between the 2 sexes were found in all the investigated
      parameters of diaphysis of tibia, except for CRT_DEN and ENDO_C (P < 0.05).
      Significant positive correlations between BW and bone weight were found (P <
      0.05). Furthermore, numerous correlations of morphometric, geometric, and
      densitometric parameters of metaphysis and diaphysis of the tibia and
      tarsometatarsus were stated (P < 0.05). In conclusion, the present investigation
      demonstrated sex-related differences in morphometric, densitometric, and
      geometric properties of tibia and tarsometatarsus in 14-mo-old ostriches.
      Numerous correleations observed between the investigated parameters have shown
      that ostrich tibia and tarsometatarsus may present a valuable model for further
      studies on bone tissue metabolism regulation in breeding birds. 

PMID- 24135602
TI  - Short periods of incubation during egg storage increase hatchability and chick
      quality in long-stored broiler eggs.
AB  - It is recognized that cool egg storage for 8 d or longer, commonly employed in
      broiler parent and commercial layer production, reduces hatchability. In this
      study, we investigated the efficacy of short periods of incubation during egg
      storage (SPIDES) in the restoration of hatchability of broiler hatching eggs
      stored for 21 d. Prolonged cool storage reduced hatchability of untreated eggs
      from 92 to 71%. The SPIDES treatment, which consisted of four 4-h preincubations
      at 4- to 5-d intervals during storage, reduced the incubation time and restored
      hatchability to 84% by lowering both early and late embryo mortality (P =
      0.0002). The SPIDES-treated embryos exhibited higher proportions of viable cells
      after each preincubation (P = 0.02), potentially alleviating the negative effects
      of storage-induced cell death on embryo development. After completion of 4
      preincubations, SPIDES embryos were advanced to intermediate primitive streak
      formation, a developmental stage previously associated with embryo mortality
      during storage. In contrast to reported preincubation methods imposed on-farm
      immediately before the eggs are first cooled, the SPIDES technique permits 4 d of
      cool storage before the initial preincubation treatment, introducing flexibility
      in the incubation protocol and enabling cool storage up to 3 wk with much
      improved hatch rates than would usually be expected. Although SPIDES chicks
      exhibited a BW equivalent to that of embryos derived from unstored eggs at hatch,
      the initial relative growth was increased as a result of SPIDES, generating a
      higher BW over the first 4 wk posthatch (P < 0.05). Single preincubations of 6
      and 12 h at 4 d of storage caused similar advances in embryo stage to the SPIDES
      treatment, but the hatchability was worse than in the untreated controls,
      suggesting small multiple preincubations during storage have a greater benefit
      than a single incubation performed on d 4 of storage. Future research regarding
      the cellular and molecular basis of physiological stress reduction in SPIDES
      embryos will yield new insights into the alleviation of early embryo mortality
      associated with egg storage. 

PMID- 24135603
TI  - An efficient method of guinea fowl sperm cryopreservation.
AB  - France is the only country that practices pedigree selection of guinea fowl for
      meat production. The increasing risk of line extinction for sanitary or breeding
      failure reasons makes clear the need for an efficient method of reproductive cell
      cryopreservation in this species. However, an efficient method of guinea fowl
      sperm freezing in secured packaging is still lacking. The aim of the present
      study was to develop such a method. Based on results previously obtained in
      chickens, different cryoprotectants and freezing/thawing processes were tested
      and then adapted to guinea fowl. Semen quality was measured by semen viability
      evaluation and then by fertility measured after intravaginal artificial
      insemination. The best results (70% fertility with frozen-thawed sperm) were
      obtained by the use of the permeant cryoprotectant agents dimethyl formamide
      combined with a freezing rate of 30 degrees C/min. The initial insemination
      frequency also affected the fertility results: 2 consecutive days of
      inseminations were needed in the first week to ensure enough filling of the utero
      vaginal glands of the guinea fowl hen and thus to get successive fertile eggs.
      Thereafter, a 2-wk insemination frequency was sufficient. This new method,
      combining biophysical (cryoprotectant agents, freeze/thaw rate) and zootechnical
      (artificial insemination frequency) features, is the first cryopreservation
      method successfully developed in secured packaging for guinea fowl sperm. This
      method is now available for the practice of gene bank conservation and male
      reproductive management. 

PMID- 24135604
TI  - Proteolytic activity alterations resulting from force-feeding in Muscovy and
      Pekin ducks.
AB  - We investigated liver protease activity in force-fed and non-force-fed ducks
      using zymography gels to better understand mechanisms underlying liver steatosis
      in palmipeds. Male Muscovy and Pekin ducks were slaughtered before and after a
      short period (13 d) while they were conventionally fed or force fed. The force
      fed regimen contained a high level of carbohydrates and was delivered in large
      doses. Main hepatic proteases (matrix metalloprotease-2, calpains, and
      cathepsins) were extracted from raw liver and specifically activated within
      electrophoretic gels. Both force-fed Muscovy and Pekin ducks presented higher
      liver weights and BW associated with lower matrix metalloprotease-2 and m-calpain
      hepatic activities. On the other hand, hepatic cathepsin activity was not
      affected by force feeding. It was concluded that Muscovy and Pekin duck hepatic
      proteases are affected similarly by the force feeding. Thus, this cannot explain
      differences observed between Muscovy and Pekin ducks regarding their ability to
      develop hepatic steatosis generally reported in literature. 

PMID- 24135605
TI  - Comparison of cook loss, shear force, and sensory descriptive profiles of
      boneless skinless white meat cooked from a frozen or thawed state.
AB  - Four replications were conducted to compare quality measurements, cook loss,
      shear force, and sensory quality attributes of cooked boneless skinless white
      meat, broiler breast fillets (pectoralis major) prepared directly from a frozen
      state or prepared from a thawed state. In each replication, fresh broiler fillets
      (removed from carcasses 6-8 h postmortem) were procured from a local commercial
      processing plant and stored in a -20 degrees C freezer until use. On the sensory
      evaluation date, fillets were cooked to an endpoint temperature of 78 degrees C
      either directly from the frozen state (thawing during cooking) or after the
      frozen samples were thawed in a refrigerator (2 degrees C) overnight (thawing
      before cooking). Cook loss and Warner-Bratzler (WB) shear force were used as
      indicators for instrumental quality measurements. Sensory quality measurements
      were conducted by trained descriptive panelists using 0 to 15 universal intensity
      scales for 8 texture and 10 flavor attributes. Results show that there were no
      differences (P > 0.05) in measurements for sensory descriptive flavor attributes
      of cooked fillets between the 2 sample thawing methods, indicating that the
      sensory flavor profiles of both methods were similar to each other. However, WB
      shear force (36.98 N), cook loss (21.2%), sensory texture attributes of
      cohesiveness (intensity score was 5.59), hardness (5.14), rate of breakdown
      (5.50), and chewiness (5.21) of the breast fillets cooked directly from the
      frozen state were significantly higher (P < 0.05) than those of the breast meat
      cooked after being thawed (30.56 N, 19.0%, 5.19, 4.78, 5.29, and 5.02,
      respectively). These results indicate that cookery directly from frozen boneless
      skinless white meat can result in different measurement values of cook loss,
      shear force, and sensory descriptive texture attributes compared with cookery
      after frozen fillets are thawed. 

PMID- 24135606
TI  - Comparison of different preenrichment broths, egg:preenrichment broth ratios, and
      surface disinfection for the detection of Salmonella enterica ssp. enterica
      serovar Enteritidis in shell eggs.
AB  - Salmonella enterica ssp. enterica serovar Enteritidis is the leading reported
      cause of Salmonella infections. Most Salmonella Enteritidis infections are
      associated with whole shell eggs and egg products. This project attempted to lay
      the foundation for improving the Food and Drug Administration's current
      Bacteriological Analytical Manual method for the detection of Salmonella
      Enteritidis in shell eggs. Two Salmonella Enteritidis isolates were used for
      comparisons among different preenrichment and enrichment media and for the
      evaluation of egg:preenrichment broth ratios for the detection of Salmonella
      Enteritidis in shell eggs. The effect of surface disinfection on the detection of
      Salmonella Enteritidis in shell eggs was also investigated. The results indicated
      that tryptic soy broth (TSB) was similar to TSB plus ferrous sulfate, but
      significantly (alpha = 0.05) better than nutrient broth, Universal Preenrichment
      broth, and buffered peptone water when used for preenrichment of Salmonella in
      shell eggs. Salmonella Enteritidis populations after enrichment with Rappaport
      Vassiliadis broth were 0.40 to 1.11 log cfu/mL of culture lower than those in
      preenrichment cultures. The reduction was statistically significant (alpha =
      0.05). Egg:broth ratios at 1:9 and 1:2 produced significantly (alpha = 0.05)
      higher Salmonella Enteritidis populations after preenrichment with TSB with
      inoculum levels at 4 cfu/100 g of eggs and 40 cfu/1,000 g of eggs than the ratio
      at 1:1. Salmonella Enteritidis populations in TSB preenrichment cultures of shell
      eggs surface-disinfected with 70% alcohol:iodine/potassium iodide solution and
      untreated control were 9.11 +/- 0.11 and 9.18 +/- 0.05 log cfu/mL, respectively,
      for SE 13-2, and 9.20 +/- 0.04 and 9.16 +/- 0.05 log cfu/mL, respectively, for SE
      CDC_2010K_1543. Surface disinfection of eggs did not reduce the sensitivity of
      detection of Salmonella Enteritidis in liquid eggs. These results could improve
      the Food and Drug Administration's current Bacteriological Analytical Manual
      method for the detection of Salmonella in shell eggs by simplifying the
      preenrichment medium and changing the sample handling before enrichment.

PMID- 24135607
TI  - Effects of frying and boiling on the formation of heterocyclic amines in braised
      chicken.
AB  - Braised chicken is a traditional ready-to-eat poultry product produced by frying
      chicken coated with maltose or honey and then boiling it in a soup that is
      circularly used. This study examined the effects of the frying time, honey
      concentration, boiling time, and cycle times of the soup on the formation of
      heterocyclic amines (HA), a class of mutagenic/carcinogenic compounds generated
      in heated muscle meat. Nine HA in chicken and recycled soups were analyzed by
      HPLC with UV and fluorescence detection. 1-Methyl-9H-pyrido[3,4-b]indole
      (Harman), 9H-pyrido[3,4-b]indole (Norharman), and 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) were detected in most samples, and the amount of
      each HA increased with the frying or boiling time. Chicken skin was found to have
      higher HA content than chicken meat. More HA were detected in the soup than in
      the chicken, in most cases. 2-Amino-3-methylimidazo[4,5-f]quinoline and 2-amino
      3,4,8-trimethylimidazoquinoxaline (4,8-DiMeIQx) were also detected in chicken and
      soup circularly boiled 20 times, and the total amount of HA reached 68.80 and
      96.98 ng/g in chicken and soup, respectively. 

PMID- 24135608
TI  - Change in the chicken eggshell cuticle with hen age and egg freshness.
AB  - For a fuller understanding of the functionality of the eggshell cuticle, we
      conducted a detailed study using a wide array of analytical techniques (scanning
      and transmission microscopy), energy dispersive x-rays, and attenuated total
      reflection-Fourier transform infrared spectroscopy to analyze the structure,
      morphology, and chemical composition of this organic coating. This study shows
      that the cuticle has a compositional gradation with an outer part richer in
      proteins and an inner part richer in sulfated polysaccharides and phosphates. It
      also shown that the cuticle composition, thickness, and degree of coverage are
      highly dependent on hen age and egg freshness. During the course of the first
      laying year, the thickness and degree of glycosylation of the cuticle decreases
      with hen age, and at the end of the laying cycle, the cuticle is significantly
      depleted in lipids. There are also well-defined compositional changes in the
      cuticle of freshly laid eggs as time passes and there is a notable increase in
      the permeability of the eggshell after 24 h due to cuticle drying. We discuss how
      these changes in the cuticle can affect the food safety of eggs in relation to
      the risk of trans-shell contamination by bacteria (i.e., Salmonellosis). 

PMID- 24135609
TI  - Characterization of integrons and their cassettes in Escherichia coli and
      Salmonella isolates from poultry in Korea.
AB  - Ninety-nine Escherichia coli and 33 Salmonella isolates were assessed for
      antimicrobial susceptibility (disc diffusion test). Sulfonamide and tetracycline
      resistance genes were identified through PCR, and class 1 and class 2 integrons
      with resistance gene cassettes were identified with PCR followed by sequencing.
      Salmonella (63.6%) and E. coli (85.8%) isolates were multidrug resistant
      (resistance to 3 or more antimicrobials), and the highest incidences of
      resistance were observed for tetracycline, nalidixic acid, and sulfamethoxazole.
      The sul1, sul2, tetA, and tetB resistance determinant genes were predominant in
      E. coli, whereas only sul2 and tetA were identified in Salmonella isolates. In
      the E. coli isolates, 54 (54.5%) class 1 integrons, 6 (6.1%) class 2 integrons,
      and 5 (5.1%) class 1 and class 2 integrons together were detected, whereas only 3
      (9.1%) integrons were found in the Salmonella serovars. Around 87% of the
      integrons in E. coli harbored resistance gene cassettes conferring resistance to
      streptomycin/spectinomycin (aadA, aminoglycoside resistance gene), trimethoprim
      (dfrA, dihydrofolate reductase gene), streptothricin [sat1 and sat2
      (streptothricin acetyltransferase), and estX (putative esterases)]. The most
      common gene cassettes were aadA1+dfrA1 and dfrA1+sat2+aadA1 in class 1 and class
      2 integrons, respectively. Other cassettes including aadA5+dfrA7, dfrA12+aadA2,
      aadA2+aadA1+dfrA12, and aadA5+aadA2/dfrA7 were also identified. Among the
      Salmonella serovars, Salmonella Malmoe harbored aadA1+dfrA1 and dfrA12+sat2+aadA1
      genes. The aadA1, aadA2, sat2, and dfrA1 had wide variation in similarity among
      themselves and from previously reported genes worldwide. The diverse gene
      cassettes could be responsible for the prominent resistance profiles observed and
      a potential source for dissemination of antimicrobial resistance determinants to
      other bacteria. 

PMID- 24135610
TI  - Breast meat quality of broiler chickens can be affected by managing the level of
      nitric oxide.
AB  - The objective of this study was to investigate the effects of nitric oxide (NO)
      on the quality of broiler chicken meat during postmortem storage. Eighteen
      broiler chickens were slaughtered and breast meat was randomly assigned to 1 of 3
      treatments including the control group, nitric oxide synthase (NOS) inhibitor
      group, and NO enhancer group. The breast samples were incubated with water, NO
      enhancer, and NO inhibitor for 1 d and then stored at 4 degrees C under
      atmospheric conditions for 4 and 7 d. Left side of breast meat was used to
      determine protein oxidation, lipid oxidation, water-holding capacity, and pH,
      whereas the right side was used for the measurement of color and drip loss.
      Breast meat from NO enhancer group showed the lowest water-holding capacity
      during refrigerated storage, whereas drip losses were not significantly (P >
      0.05) different among 3 treatments. Lipid oxidation showed a significant
      difference (P < 0.05) only at 7 d in which NOS inhibitor group showed the
      highest, whereas the NO enhancer group showed the lowest levels of lipid
      oxidation. Carbonyl content in NO enhancer group was significantly higher than
      the control and NOS inhibitor treatment at 1 and 4 d of refrigerated storage.
      Lightness of breast meat in the NOS inhibitor group was greater, whereas redness
      was lower than the control and NO enhancer group at 4 and 7 d of refrigerated
      storage. The ultimate pH of 3 treatments was not significantly (P > 0.05)
      different from one another. These data indicate that NO could play a significant
      role in modulating the quality of fresh broiler breast meat during refrigerated
      storage. 

PMID- 24135611
TI  - Aspects of the nutritional value of cooked Egyptian goose (Alopochen aegyptiacus)
      meat compared with other well-known fowl species.
AB  - There is no scientific research regarding Egyptian goose (Alopochen aegyptiacus)
      meat; therefore, a chemical analysis to establish the nutritional characteristics
      of the breast portion is described. Meat from guinea fowl, Pekin duck, ostrich,
      and broiler chicken were used as a reference. The high intramuscular fat content
      of Egyptian goose meat (5.6 g/100 g) may be linked to the fact that this species
      relies on fat for heat insulation and buoyancy. Egyptian goose meat is very high
      in polyunsaturated fatty acids (39.7%). The polyunsaturated fatty acid/saturated
      fatty acid ratio is within the recommendations (>0.4), although the n-6/n-3 ratio
      is higher than the suggested value of 5. The high Fe content of 7.5 mg/100 g is
      the differentiating factor within the mineral compositions and is related to the
      physical activity endured by the breast muscle of Egyptian geese. This study
      provides new insight into the nutritional characteristics of a meat species
      providing crucial information that is, as of yet, not available in the
      literature.

PMID- 24135612
TI  - Prevalence and concentration of Salmonella and Campylobacter in the processing
      environment of small-scale pastured broiler farms.
AB  - A growing niche in the locally grown food movement is the small-scale production
      of broiler chickens using the pasture-raised poultry production model. Limited
      research exists that focuses on Salmonella and Campylobacter contamination in the
      environment associated with on-farm processing of pasture-raised broilers. The
      objective of this study was to establish data relative to Salmonella and
      Campylobacter prevalence and concentration in soil and mortality compost
      resulting from prior processing waste disposal in the small-scale, on-farm
      broiler processing environment. Salmonella and Campylobacter concentrations were
      determined in soil (n = 42), compost (n = 39), and processing wastewater (PWW; n
      = 46) samples from 4 small broiler farms using a 3-tube most probable number
      (MPN) method for Salmonella and direct plating method for Campylobacter.
      Salmonella prevalence and concentration (mean log10 MPN per sample weight or
      volume) in soil [60%, 0.97 (95% CI: 0.66 to 1.27)], compost [64%, 0.95 (95% CI:
      0.66 to 1.24)], and wastewater [48%, 1.29 (95% CI: 0.87 to 1.71)] were not
      significantly different (P > 0.05). Although Campylobacter prevalence was not
      significantly different by sample type (64.3, 64.3, and 45.7% in soil, compost,
      and PWW, respectively), the concentration (mean log10 cfu) of this pathogen was
      significantly lower (P < 0.05) in wastewater [2.19 (95% CI: 0.36 to 3.03)]
      samples compared with soil [3.08 (95% CI: 2.23 to 3.94)], and compost [3.83 (95%
      CI: 2.71 to 4.95)]. These data provide insight into small-scale poultry
      production waste disposal practices and provides a record of data that may serve
      as a guide for future improvement of these practices. Further research is needed
      regarding the small-scale broiler production environment in relation to improving
      disposal of processing waste for optimum control of human pathogens. 

PMID- 24135614
TI  - Profit or patients' health benefit? Exploring the heterogeneity in physician
      altruism.
AB  - This paper investigates physician altruism toward patients' health benefit using
      behavioral data from Hennig-Schmidt et al.'s (2011) laboratory experiment. In the
      experiment, medical students in the role of physicians decide on the provision of
      medical services. The experimental setup allows us to identify the influence of
      profits and patients' health benefit on the choice of medical treatment. We
      estimate physician altruism, the weight individuals attach to patients' health
      benefit, by fitting mixed logit and multinomial logit regression models to the
      experimental data. Estimation results provide evidence for physician altruism. We
      find, however, substantial variation in the degree of physician altruism. We also
      discuss some implications of our results for the design of physician payment
      schemes in the light of the theoretical literature. 

PMID- 24135613
TI  - Human and mouse ZFP57 proteins are functionally interchangeable in maintaining
      genomic imprinting at multiple imprinted regions in mouse ES cells.
AB  - Genomic imprinting is a common epigenetic phenomenon in mammals. Dysregulation of
      genomic imprinting has been implicated in a variety of human diseases. ZFP57 is a
      master regulator in genomic imprinting. Loss of ZFP57 causes loss of DNA
      methylation imprint at multiple imprinted regions in mouse embryos, as well as in
      embryonic stem (ES) cells. Similarly, mutations in human ZFP57 result in
      hypomethylation at many imprinted regions and are associated with transient
      neonatal diabetes and other human diseases. Mouse and human Zfp57 genes are
      located in the same syntenic block. However, mouse and human ZFP57 proteins only
      display about 50% sequence identity with different number of zinc fingers. It is
      not clear if they share similar mechanisms in maintaining genomic imprinting.
      Here we report that mouse and human ZFP57 proteins are functionally
      interchangeable. Expression of exogenous wild-type human ZFP57 could maintain DNA
      methylation imprint at three imprinted regions in mouse ES cells in the absence
      of endogenous mouse ZFP57. However, mutant human ZFP57 proteins containing the
      mutations found in human patients could not substitute for endogenous mouse ZFP57
      in maintaining genomic imprinting in ES cells. Like mouse ZFP57, human ZFP57 and
      its mutant proteins could bind to mouse KAP1, the universal cofactor for KRAB
      zinc finger proteins, in mouse ES cells. Thus, we conclude that mouse and human
      ZFP57 are orthologs despite relatively low sequence identity and mouse ES cell
      system that we had established before is a valuable system for functional
      analyses of wild-type and mutant human ZFP57 proteins. 

PMID- 24135615
TI  - Increasing organ donation via changes in the default choice or allocation rule.
AB  - This research utilizes a laboratory experiment to evaluate the effectiveness of
      alternative public policies targeted at increasing the rate of deceased donor
      organ donation. The experiment includes treatments across different default
      choices and organ allocation rules inspired by the donor registration systems
      applied in different countries. Our results indicate that the opt-out with
      priority rule system generates the largest increase in organ donation relative to
      an opt-in only program. However, sizeable gains are achievable using either a
      priority rule or opt-out program separately, with the opt-out rule generating
      approximately 80% of the benefits achieved under a priority rule program. 

PMID- 24135616
TI  - Symptoms of depression and anxiety in anorexia nervosa: links with plasma
      tryptophan and serotonin metabolism.
AB  - Depressive, anxiety and obsessive symptoms frequently co-occur with anorexia
      nervosa (AN). The relationship between these clinical manifestations and the
      biological changes caused by starvation is not well understood. It has been
      hypothesised that reduced availability of tryptophan (TRP) could reduce serotonin
      activity and thus trigger these comorbid symptoms. The aim of this study, during
      re-feeding in individuals with AN, was to analyse covariations across measures of
      nutritional status, depressive and anxiety symptoms, and peripheral serotonin
      markers. Depressive and anxiety symptoms, nutritional status and serotonin
      markers--whole blood serotonin content, plasma TRP and the ratio between TRP and
      large neutral amino acids--were assessed for 42 AN participants at admission to
      inpatient treatment and after re-feeding. Biological measures were compared to
      those obtained in 42 non-eating disordered subjects. For those with AN,
      psychological, nutritional and biological parameters improved significantly
      during hospitalisation. Levels of serotonin markers were significantly lower in
      the AN group compared to the control group, at admission and at discharge.
      Increase in the TRP/LNAA ratio was correlated with a decrease in depressive
      symptoms. In addition, there was a positive correlation between serotonin levels
      and symptoms of both anxiety and depression at discharge. We speculate that
      enhanced TRP availability during re-feeding, as a result of the increase in the
      TRP/LNAA ratio, could restore serotonin neurotransmission and lead to a decrease
      in depressive symptoms. The association between serotonin and anxiety and
      depressive symptoms would be consistent with numerous observations indicating
      abnormal functioning of the serotoninergic system in AN.

PMID- 24135617
TI  - Antibody-drug conjugate model fast characterization by LC-MS following IdeS
      proteolytic digestion.
AB  - Here we report the design and production of an antibody-fluorophore conjugate
      (AFC) as a non-toxic model of an antibody-drug conjugate (ADC). This AFC is based
      on the conjugation of dansyl sulfonamide ethyl amine (DSEA )-linker maleimide on
      interchain cysteines of trastuzumab used as a reference antibody. The resulting
      AFC was first characterized by routine analytical methods (SEC, SDS-PAGE, CE-SDS,
      HIC and native MS), resulting in similar chromatograms,electropherograms and mass
      spectra to those reported for hinge Cys-linked ADCs. IdeS digestion of the AFC
      was then performed, followed by reduction and analysis by liquid chromatography
      coupled to mass spectrometry analysis. Dye loading and distribution on light
      chain and Fd fragments were calculated, as well as the average dye to antibody
      ratio (DAR) for both monomeric and multimeric species. In addition, by analyzing
      the Fc fragment in the same run, full glycoprofiling and demonstration of the
      absence of additional conjugation was easily achieved. As for naked antibodies
      and Fc-fusion proteins, IdeS proteolytic digestion may rapidly become a reference
      analytical method at all stages of ADC discovery, preclinical and clinical
      development. The method can be routinely used for comparability assays,
      formulation, process scale-up and transfer, and to define critical quality
      attributes in a quality-by-design approach.

PMID- 24135618
TI  - Prevalence and predictors of nonadherence to hemodialysis.
AB  - BACKGROUND: The prevalence of nonadherence to dialysis (NAD) presents a wide
      variation, depending on the parameters used and demographic regions studied. This
      study aimed to assess the prevalence and predictors of NAD of patients with
      chronic kidney disease undergoing hemodialysis (HD). MATERIALS AND METHODS: This
      was a cross-sectional study with 255 adult patients receiving HD for >3 months.
      Skipping a session per month, shortening a session for at least 10 min,
      phosphorus >7.5 mg/dl, potassium >6.0 mmol/l and interdialytic weight gain (IDWG)
      >5.7% of body weight were indicative of NAD. The association of sociodemographic
      and clinical variables with NAD was assessed using logistic regression. RESULTS:
      Mean age was 50 +/- 13.1 years, 62.7% were male, 85.5% were of African descent
      and 62% were married. The prevalence rates of NAD were: 49% of shortening
      sessions, 18% of hyperkalemia, 12% of hyperphosphatemia, 9% of IDWG >5.7% of dry
      weight and 8% of skipping HD. Independent predictors of NAD were: age <=50 years,
      not being married, living alone, living in Salvador, attending dialysis without a
      companion, ethnic African descent, Kt/V <1.3 and residual diuresis <100 ml/day.
      CONCLUSION: NAD is frequent and distinct sociodemographic and clinical variables
      predict different parameters.

PMID- 24135619
TI  - Cutaneous Mycobacterium chelonae infection in a rheumatoid arthritis patient
      treated with etanercept.

PMID- 24135621
TI  - A multicenter randomized controlled trial evaluating balneotherapy in patients
      with advanced chronic venous insufficiency.
AB  - BACKGROUND: Apart from compression therapy, physical therapy has scarcely been
      evaluated in the treatment of chronic venous disorders (CVDs). Spa treatment is a
      popular way to administer physical therapy for CVDs in France, but its efficacy
      has not yet been assessed in a large trial. The objective was to assess the
      efficacy of spa therapy for patients with advanced CVD (CEAP clinical classes C4
      C5). METHODS: This was a single-blind (treatment concealed to the investigators)
      randomized, multicenter, controlled trial (French spa resorts). Inclusion
      criteria were primary or post-thrombotic CVD with skin changes but no active
      ulcer (C4a, C4b, or C5). The treated group had the usual 3-week spa treatment
      course soon after randomization; the control group had spa treatment after the 1
      year comparison period. All patients continued their usual medical care including
      wearing compression stockings. Treatment consisted of four balneotherapy sessions
      per day for 6 days a week. Follow-up was performed at 6, 12 and 18 months by
      independent blinded investigators. The main outcome criterion was the incidence
      of leg ulcers at 12 months. Secondary criteria were a modified version of the
      Venous Clinical Severity Score, a visual analog scale for leg symptoms, and the
      Chronic Venous Insufficiency Questionnaire 2 and EuroQol 5D quality-of-life
      autoquestionnaires. RESULTS: Four hundred twenty-five subjects were enrolled: 214
      in the treatment group (Spa) and 211 in the control group (Ctr); they were
      similar at baseline regarding their demographic characteristics, the severity of
      the CVD, and the outcome variables. At 1 year, the incidence of leg ulcers was
      not statistically different (Spa: +9.3%; 95% confidence interval [CI], +5.6 -
      +14.3; Ctr: +6.1%; 95% CI, +3.2 - +10.4), whereas the Venous Clinical Severity
      Score improved significantly in the treatment group (Spa: -1.2; 95% CI, -1.6 - 
      0.8; Ctr: -0.6; 95% CI, -1.0 - -0.2; P = .04). A significant difference favoring
      spa treatment was found regarding symptoms after 1 year (Spa: -0.03; 95% CI, 
      0.57 - +0.51; Ctr: +0.87; 95% CI,+0.46 - +1.26; P = .009). EuroQol 5D improved in
      the treatment group (Spa: +0.01; 95% CI, -0.02 - +0.04) while it worsened (Ctr: 
      0.07; 95% CI, -0.10 - -0.04) in the control group (P < .001). A similar pattern
      was found for the Chronic Venous Insufficiency Questionnaire 2 scale (Spa: -2.0;
      95% CI, -4.4 - +0.4; Ctr: +2.4; 95% CI, +0.2 - +4.7; P = .008). The control
      patients showed similar improvements in clinical severity, symptoms, and quality
      of life after their own spa treatment (day 547). CONCLUSIONS: In this study, the
      incidence of leg ulcers was not reduced after a 3-week spa therapy course.
      Nevertheless, our study demonstrates that spa therapy provides a significant and
      substantial improvement in clinical status, symptoms, and quality of life of
      patients with advanced venous insufficiency for at least 1 year.

PMID- 24135620
TI  - Reintervention after thoracic endovascular aortic repair of complicated aortic
      dissection.
AB  - OBJECTIVE: This study assessed predictive factors for reintervention after
      thoracic endovascular aortic repair (TEVAR) for complicated aortic dissection (C
      AD). METHODS: An institutional review of consecutive TEVAR for C-AD was
      performed. RESULTS: Between 2000 and 2011, 41 patients underwent TEVAR for a C-AD
      involving the descending thoracic aorta. Primary indications included aneurysm
      >55 mm in 24, rapid aneurysmal enlargement or impending rupture in 6, saccular
      aneurysm >20 mm in 1, malperfusion in 1, intractable chest pain in 3, and rupture
      in 6. Technical success was achieved in 100%. The 30-day mortality rate was 5% (n
      = 2). Fourteen secondary procedures were performed in 13 patients (32%) for
      indications of device migration in 2, proximal type I endoleak in 5, distal type
      I endoleak in 2, type II endoleak in 1, aneurysmal evolution of the descending
      thoracic aorta in 2, aneurysmal expansion of the dissected abdominal aorta in 1,
      and retrograde dissection in 1. Multivariate analysis demonstrated that
      oversizing >=20% (odds ratio [OR], 16; P = .011), bare-spring stent in the
      proximal landing zone of the stent graft (OR, 12; P = .032), and anticoagulant
      therapy (OR, 78; P = .03) were significant factors for reintervention. On
      univariate analysis, large aneurysm was a risk factor for reintervention (P =
      .002), whereas complete false lumen thrombosis at the stent graft level was
      protective (P < .05). CONCLUSIONS: This study confirms the feasibility of TEVAR
      for C-AD, although the rate of reintervention is high. Excessive oversizing, a
      bare-spring stent graft in the proximal landing zone, large aortic dilatation,
      and anticoagulant therapy were factors associated with reintervention. Complete
      false lumen thrombosis at the stent graft level was protective.

PMID- 24135622
TI  - Heparin-induced thrombocytopenia causing graft thrombosis and bowel ischemia
      postendovascular aneurysm repair.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenia
      resulting from prior heparin exposure. It can be associated with limb- or life
      threatening thrombotic events. Patients undergoing any vascular procedures
      including endovascular procedures that require heparin administration are at
      risk. There is very little reported in the literature with regards to thrombosis
      associated with HIT after endovascular aortic aneurysm repair. All reported cases
      of HIT thrombosis presented as acute arterial lower limb ischemia or deep vein
      thrombosis. In this report, we present a case of HIT complicated by stent graft
      thrombosis and bowel ischemia. 

PMID- 24135623
TI  - C-reactive protein polymorphism rs3091244 is associated with abdominal aortic
      aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) formation involves an inflammatory
      process with a strong genetic background. C-reactive protein (CRP) regulates
      inflammation and is elevated in patients with AAA. The aim of this study was to
      investigate the association of the triallelic (C, A, and T alleles) rs3091244
      functional CRP single nucleotide polymorphism (SNP) with AAA. METHODS: This was a
      case-control study involving two independent populations: 351 AAA patients (mean
      aortic diameter, 6.25 +/- 1.47 cm) and 391 controls (mean diameter, 2.4 +/- 0.2
      cm) were recruited from Greece (the main cohort); and 371 patients (mean
      diameter, 5.4 +/- 1.0 cm) and 362 controls (mean diameter, 2.4 +/- 0.6 cm) were
      recruited from the United Kingdom (replication cohort). The frequency of the
      functional triallelic (C, T, and A alleles) rs3091244 polymorphism was analyzed
      in univariate and adjusted (for cardiovascular risk factors) analyses, assuming
      that the rare T and A alleles have similar functional properties (pooled analysis
      for T and A). Three groups were constructed: group A included those with the rare
      T and A alleles (genotypes TT, AA, and TA), group B included heterozygotes for
      the C allele (CT, CA), and group C included C allele homozygotes (CC, reference
      genotype). Finally, meta-analysis of the two populations was performed together
      with previously reported results. RESULTS: Genotype distributions differed
      significantly between cases and controls in both cohorts (P < .001 and P = .001).
      Adjusted analysis (for all aneurysm-related risk-factors) showed an estimated
      odds ratio of 4.88 (95% confidence interval [CI], 2.96-8.04) for SNP group A and
      2.38 (95% CI, 1.69-3.36) for SNP group B (P < .001 in both cases) in the initial
      cohort and 2.07 (95% CI, 1.33-3.21) for SNP group A and 1.70 (95% CI, 1.21-2.39)
      for SNP group B (P = .001 and .002) in the replication cohort. The SNP group A
      patients among the main cohort also had higher CRP levels (median, 26;
      interquartile range, 17-52 mg/L vs median, 4; interquartile range, 4-12 mg/L; P <
      .001). Aneurysms >5.5 cm were significantly more frequent among the SNP groups A
      and B compared with C allele homozygotes both in the main and the replication
      cohorts (P < .001 and P = .001, respectively). Meta-analysis of the two
      populations with previously reported results showed a positive association
      between minor-allele and aneurysm presence with an odds ratio of 1.47 (95% CI,
      1.01-2.14; I(2) = 83.1%; P = .04). CONCLUSIONS: The rare T and A alleles were
      significantly related with AAA presence in both populations and correlated with
      higher CRP levels and AAA diameter.

PMID- 24135624
TI  - Pharmacologic attenuation of the hyperdynamic response to supraceliac aortic
      clamping.
AB  - BACKGROUND: Aortic occlusion is accompanied by a hyperdynamic cardiovascular
      response secondary to increased systemic vascular resistance and increased
      cardiac output. This study was designed primarily to determine the safety and
      cardiovascular response to hydrogen sulfide (H2S; HS) administration with
      supraceliac aortic cross-clamp and, secondarily, on short-duration resuscitation.
      METHODS: A validated porcine model (five sham swine compared with five controls)
      demonstrated a significant hyperdynamic cardiovascular response to 35% blood
      volume hemorrhage, 50-minute suprarenal aortic cross-clamping, and 6-hour
      resuscitation. Eight additional experimental swine were administered HS at 4
      mg/min during aortic cross-clamping. RESULTS: During the cross-clamp period,
      hemodynamic curves of mean arterial pressure and heart rate demonstrated a
      blunting effect with HS administration, with a significant decrease being seen
      with mean arterial pressure at the end of the cross-clamp period (120 vs 149 mm
      Hg; P = .04). Resuscitation requirements were significantly reduced at 6 hours
      because the HS cohort received 8 L less crystalloid (P = .001) and 10.4 mg less
      epinephrine (P < .001). There was not a significant change in cardiac output,
      systemic vascular resistance, pulmonary vascular resistance, or pathologic liver
      analysis. CONCLUSIONS: The administration of HS during the 50 minutes of
      supraceliac aortic cross-clamp significantly reduced stress of the left heart. On
      clamp release, HS significantly reduced the need for volume and pressors. HS has
      positive benefits during cross-clamp and subsequent resuscitation, demonstrating
      that targeted pharmacologic therapy is possible to minimize adverse physiologic
      changes with aortic occlusion.

PMID- 24135625
TI  - Effect of organic matter and moisture on the calorific value of solid wastes: an
      update of the Tanner diagram.
AB  - Objective of the work was to experimentally determine the effect of the organic
      matter and moisture contents on the calorific value of organic solid wastes. Nine
      substrates (i.e. newsprint, biodried municipal solid wastes, municipal solid
      waste derived composts, wastewater sludges, and sea weed derived compost), with
      organic matter contents that ranged from 12% to 91% (dry weight) were used in the
      experiments. All substrates were dried and ground and deionized water was
      artificially added in order to achieve certain target moisture contents per
      substrate. The higher heating value (HHV) was, then, determined experimentally
      for each sample using a bomb calorimeter. Best reduced models were developed to
      describe the higher and lower heating values as a function of organic matter, ash
      and moisture contents. A triangular plot was constructed and the self-combustion
      area was determined and compared to that of the Tanner diagram. Response surfaces
      were drawn to visually assess the effect of organic matter and moisture contents
      on the calorific value of the wastes. 

PMID- 24135626
TI  - Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds
      to low levels of arsenite.
AB  - Inorganic arsenite (iAs(3+)) is a two-edged sword. iAs(3+) is a well-known human
      carcinogen; nevertheless, it has been used as a therapeutic drug for acute
      promyelocytic leukemia (APL), which is caused by a fusion protein comprising
      retinoic acid receptor-alpha and promyelocytic leukemia (PML). PML, a nuclear
      transcription factor, has a RING finger domain with densely positioned cysteine
      residues. To examine PML-modulated cellular responses to iAs(3+), CHO-K1 and
      HEK293 cells were each used to establish cell lines that expressed ectopic human
      PML. Overexpression of PML increased susceptibility to iAs(3+) in CHO-K1 cells,
      but not in HEK293 cells. Exposure of PML-transfected cells to iAs(3+) caused PML
      to change from a soluble form to less soluble forms, and this modification of PML
      was observable even with just 0.1 MUM iAs(3+) (7.5 ppb). Western blot and
      immunofluorescent microscopic analyses revealed that the biochemical changes of
      PML were caused at least in part by conjugation with small ubiquitin-like
      modifier proteins (SUMOylation). A luciferase reporter gene was used to
      investigate whether modification of PML was caused by oxidative stress or
      activation of antioxidant response element (ARE) in CHO-K1 cells. Modification of
      PML protein occurred faster than activation of the ARE in response to iAs(3+),
      suggesting that PML was not modified as a consequence of oxidative stress-induced
      ARE activation.

PMID- 24135627
TI  - Apathy in aging: are lack of interest and lack of initiative dissociable?
AB  - Apathy is common in aging and generally defined on the basis of three dimensions:
      lack of initiative, lack of interest and emotional blunting. Curiously, no study
      until now has examined the associations and dissociations between these
      dimensions in elderly people (with or without dementia). These questions were
      addressed in two studies. In the first study, we explored the distribution of
      scores and the relationships between the three dimensions of apathy in 56
      patients with dementia, focusing mainly on lack of initiative and lack of
      interest. Apathy was hetero-evaluated with the Apathy Inventory (AI), a scale
      widely used to assess the apathy dimensions in aging. In the second study, given
      the AI's limitations, we investigated in more detail the relationship between
      lack of initiative and interest in 115 elderly people using a new questionnaire
      specifically designed to assess these two dimensions. Results showed that lack of
      initiative was closely related to lack of interest (Study 1). Although we used a
      more specific questionnaire, these facets of apathy did not constitute two
      separable dimensions, but reflected a common main factor of apathy in aging
      (Study 2). Thus, the distinction between lack of initiative and lack of interest
      seems questionable. Only a multifactorial approach that includes the various
      psychological factors involved in apathy would enable one to gain a better
      understanding of the different manifestations of apathy and to highlight possible
      dissociations between them. 

PMID- 24135628
TI  - Urban lymphatic filariasis in the city of Tanga, Tanzania, after seven rounds of
      mass drug administration.
AB  - Urban lymphatic filariasis (LF) has been listed among the challenges to the
      ongoing global efforts to eliminate LF. This is partly because the control
      strategies developed for rural areas - where most LF occurs - do not easily
      comply with human organization and behaviour in urban areas, and partly because
      the urban vectors thrive and proliferate in poorly planned urban settlements.
      This study investigated LF infection, disease and transmission in the medium
      sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds
      of mass drug administration (MDA). Three representative sites with varying
      distance from the city centre were selected for the study. Pupils from one public
      primary school at each site were screened for circulating filarial antigens (CFA;
      marker of adult worm infection) and antibodies to Bm14 (marker of exposure to
      transmission). Community members were examined for CFA, microfilariae and chronic
      manifestations. Questionnaires were administered to pupils and heads of community
      households, and vector surveys were carried out in selected households. Although
      there was evidence of considerable reduction in infection and transmission, there
      was still LF in the city, with mf and CFA prevalences well above the cut-off
      levels for stopping MDA. In this respect, the LF situation resembled that seen in
      nearby rural areas outside the city. The study emphasizes the importance of
      motivating the urban individuals to engage and comply with the full range of LF
      intervention measures (MDAs, use of mosquito proofing measures including bed
      nets, environmental sanitation to prevent vector breeding) in order to reach
      successful LF control in the city. The high LF disease burden noted, despite the
      reduction in infection and transmission, moreover emphasizes the importance of
      allocating resources for morbidity management, to ensure true elimination of LF
      as a public health problem. 

PMID- 24135629
TI  - A novel llama antibody targeting Fn14 exhibits anti-metastatic activity in vivo.
AB  - Expression of fibroblast growth factor (FGF)-inducible 14 (Fn14), a member of the
      tumor necrosis factor receptor superfamily, is typically low in healthy adult
      organisms, but strong Fn14 expression is induced in tissue injury and tissue
      remodeling. High Fn14 expression is also observed in solid tumors, which is why
      this receptor is under consideration as a therapeutic target in oncology. Here,
      we describe various novel mouse-human cross-reactive llama-derived recombinant
      Fn14-specific antibodies (5B6, 18D1, 4G5) harboring the human IgG1 Fc domain. In
      contrast to recombinant variants of the established Fn14-specific antibodies
      PDL192 and P4A8, all three llama-derived antibodies efficiently bound to the W42A
      and R56P mutants of human Fn14. 18D1 and 4G5, but not 5B6, efficiently blocked
      TNF-like weak inducer of apoptosis(TWEA K) binding at low concentrations (0.2-2
      MUg/ml). Oligomerization and Fcgamma receptor (FcgammaR) binding converted all
      antibodies into strong Fn14 agonists. Variants of 18D1 with enhanced and reduced
      antibody-dependent cell-mediated cytotoxicity (ADCC) activity were further
      analyzed in vivo with respect to their effect on metastasis. In a xenogeneic
      model using human colon carcinoma cancer cells, both antibody variants were
      effective in reducing metastasis to the liver. In contrast, only the 18D1 variant
      with enhanced ADCC activity, but not its ADCC-defective counterpart, suppressed
      lung metastasis in the RE NCA model. In sum, this suggests that Fn14 targeting
      might primarily act by triggering of antibody effector functions, but also by
      blockade of TWEA K-Fn14 interaction in some cases

PMID- 24135630
TI  - High-throughput glycosylation analysis of therapeutic immunoglobulin G by
      capillary gel electrophoresis using a DNA analyzer.
AB  - The Fc glycosylation of therapeutic antibodies is crucial for their effector
      functions and their behavior in pharmacokinetics and pharmacodynamics. To monitor
      the Fc glycosylation in bioprocess development and characterization,high
      throughput techniques for glycosylation analysis are needed. Here, we describe
      the development of a largely automated high-throughput glycosylation profiling
      method with multiplexing capillary-gel-electrophoresis (CGE) with laser induced
      fluorescence (LIF) detection using a DNA analyzer. After PNGaseF digestion, the
      released glycans were labeled with 9-aminopyrene-1,3,6-trisulfonic acid (APTS) in
      96-well plates, which was followed by the simultaneous analysis of up to 48
      samples. The peak assignment was conducted by HILIC-UPLC-MS/MS of the APTS
      labeled glycans combined with peak fractionation and subsequent CGE-LIF analysis
      of the MS-characterized fractions. Quantitative data evaluation of the various
      IgG glycans was performed automatically using an in-house developed software
      solution. The excellent method accuracy and repeatability of the test system was
      verified by comparison with two UPLC-based methods for glycan analysis. Finally,
      the practical value of the developed method was demonstrated by analyzing the
      antibody glycosylation profiles from fermentation broths after small scale
      protein A purification.

PMID- 24135631
TI  - A dual-targeting triplebody mediates preferential redirected lysis of antigen
      double-positive over single-positive leukemic cells.
AB  - The single-chain triplebody HLA-ds16-hu19 consists of three single-chain Fv
      (scFv) antibody fragments connected in a single polypeptide chain. This protein
      with dual-targeting capacity mediated preferential lysis of antigen double
      positive(dp) over single-positive (sp) leukemic cells by recruitment of natural
      killer (NK) cells as effectors. The two distal scFv modules were specific for the
      histocompatibility protein HLA-DR and the lymphoid antigen CD19, the central one
      for the Fc gamma receptor CD16. In antibody-dependent cellular cytotoxicity
      (ADCC) experiments with a mixture of leukemic target cells comprising both HLA-DR
      sp HuT-78 or Kasumi-1 cells and (HLA-DR plus CD19) dp SEM cells, the triplebody
      mediated preferential lysis of the dp cells even when the sp cells were present
      in <= 20-fold numerical excess.The triplebody promoted equal lysis of SEM cells
      at 2.5-fold and 19.5-fold lower concentrations than the parental antibodies
      specific for HLA-DR and CD19, respectively. Finally, the triplebody also
      eliminated primary leukemic cells at lower concentrations than an equimolar
      mixture of bispecific single-chain Fv fragments (bsscFvs) separately addressing
      each target antigen (hu19-ds16 and HLA-ds16). The increased selectivity of
      targeting and the preferential lysis of dp over sp cells achieved by dual
      targeting open attractive new perspectives for the use of dual-targeting agents
      in cancer therapy.

PMID- 24135632
TI  - 18F-FACBC compared with 11C-choline PET/CT in patients with biochemical relapse
      after radical prostatectomy: a prospective study in 28 patients.
AB  - INTRODUCTION: The aim of our study was to compare the detection rate of anti-3
      18F-FACBC PET/CT in comparison with 11C-choline PET/CT in the evaluation of
      disease recurrence of PCa after radical prostatectomy. PATIENTS AND METHODS:
      Twenty-eight consecutive patients with biochemical relapse after radical
      prostatectomy were submitted to anti-3-18F-FACBC PET/CT and 11C-choline PET/CT to
      evaluate the site of disease recurrence. Androgen deprivation therapy was avoided
      in all cases. The primary end point was the overall detection rate of the 2
      radiotracers. A patient-based analysis and a lesion-based analysis was performed.
      The target to background ratio (TBR) of each lesion was reported. RESULTS: At the
      time of PET scan, mean age was 67 years and mean prostate specific antigen (PSA)
      relapse was 2.9 ng/mL (range: 0.2-14.6). In patient-based analyses, 11C-choline
      PET/CT was positive in 5 patients and negative in 23 (detection rate = 17.8%) and
      anti-3-18F-FACBC PET/CT was positive in 10 patients and negative in 18 (detection
      rate = 35.7%). All lesions that were positive using 11C-choline were positive
      using anti-3-18F-FACBC PET/CT but with the latter radiotracer, 11 (61.1%)
      additional tumors were identified including 5 (17.8%) additional patients. The
      TBR of anti-3-18F-FACBC was greater than 11C-choline in 15 of 18 lesions,
      confirming a better image quality and contrast. CONCLUSION: This preliminary
      study demonstrated that the detection rate of anti-3-18F-FACBC PET/CT is greater
      in comparison with 11C-choline, with approximately 20% of additional patients and
      approximately 60% additional lesions detected. Further studies, however, are
      required to assess the exact added value of this new tracer.

PMID- 24135633
TI  - Reversible posterior leukoencephalopathy syndrome induced by axitinib.

PMID- 24135634
TI  - Unusual biotransformation products of the sesquiterpene lactone budlein A by
      Aspergillus species.
AB  - Biotransformation of chemicals by microorganisms can be effective in increasing
      chemical diversity. Some fungi have been described to be useful for the
      biotransformation of sesquiterpene lactones. Nevertheless, in most cases, only
      minor or simple transformations of functional groups have been observed. Budlein
      A is a sesquiterpene lactone found in high amounts in American sunflower-like
      species of the genus Viguiera (Asteraceae). It shows important biological effects
      like in vitro and in vivo anti-inflammatory activity, as well as cytotoxicity
      against cancer cell lines. With the aim to obtain potentially bioactive
      derivatives of budlein A and taking into account that obtaining semi-synthetic
      analogues is a very complex task, the capability of soil fungi to promote
      biotransformation was investigated. In this work, the biotransformation of
      budlein A by the soil fungi Aspergillus terreus and A. niger affording three
      unusual sesquiterpenoid derivatives with carbon skeletons is reported. The
      chemical structures of the compounds were elucidated by 1D and 2D NMR
      spectrometry and HR-ESI-MS. The stereochemistry and molecular conformation of one
      derivative was assessed by molecular modeling techniques. The fungal metabolites
      displayed a reduced cytotoxicity against HL-60 cells when compared to the
      original natural product. The results show the versatility of microbial-catalyzed
      biotransformations leading to unusual derivatives. 

PMID- 24135636
TI  - Depth discrimination method based on a multirow linear array detector for push
      broom Compton scatter imaging.
AB  - A depth discrimination method is devised based on a multirow linear array
      detector for push-broom Compton scatter imaging. Two or more rows of detector
      modules are placed at different positions towards a sample. An improved parallel
      hole collimator is fixed in front of the modules to restrict their fields of
      view. The depth information could be indicated by comparing the signal
      differences. In addition, an available detector and several related simulations
      using GEANT4 are given to support the method well. 

PMID- 24135635
TI  - Life dissatisfaction burden is associated with a poor surgical outcome among
      lumbar spinal stenosis patients: a 5-year follow-up study.
AB  - Dissatisfaction with life has been found to be associated with somatic health and
      the short-term surgery outcome in lumbar spinal stenosis (LSS) patients. This
      study investigated the effects of the long-term life dissatisfaction burden on
      the surgery outcome in LSS patients with a 5-year follow-up. This was a
      prospective clinical study. Altogether, 102 patients who underwent decompressive
      surgery completed a set of questionnaires preoperatively, 3 and 6 months, and 1,
      2 and 5 years after the surgery. The final study population at the 5-year follow
      up included 67 patients. The mean age of the patients was 67 years and 35% of the
      patients were men. Life satisfaction was evaluated using a four-item Life
      Satisfaction Scale. The life dissatisfaction burden was the sum of all six life
      satisfaction scores recorded during the follow-up. The outcome of surgery was
      evaluated using the Oswestry Disability Index (ODI), pain evaluation (Visual
      Analogue Scale; VAS), overall satisfaction with the surgery and self-reported
      walking capacity. In linear regression, the long-term life dissatisfaction burden
      was associated with the 5-year ODI, even after adjusting for age, sex, marital
      status, preoperative ODI and the 5-year VAS. It was not associated with the 5
      year VAS score. Monitoring the life satisfaction of surgically treated LSS
      patients may enable detection of those at risk of a poorer surgery outcome. 

PMID- 24135637
TI  - Determination of the biodistribution and dosimetry of 123I-FP-CIT in male
      patients with suspected Parkinsonism or Lewy body dementia using planar and
      combined planar and SPECT/CT imaging.
AB  - In this study, (123)I-FP-CIT biodistribution and dosimetry was determined in 10
      adult male patients using planar gamma camera imaging alone or in combination
      with single photon emission computed tomography /X-ray computed tomography
      (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging
      resulted in significantly different estimates of organ-absorbed doses compared to
      estimates based on planar imaging alone. We conclude that the use of
      complementary SPECT/CT measurements in biodistribution studies is valuable for
      determining the organ doses more accurately. 

PMID- 24135638
TI  - The role of hormones in the aging of plants - a mini-review.
AB  - BACKGROUND: In plants, the final stage of organ development is termed senescence.
      This is a deterioration process that leads to the decay of tissues and organs,
      and that, in the case of annual, biennial and/or monocarpic plants, leads to the
      death of the plant itself. The main function of leaf senescence is nutrient
      recycle and, since this confers an adaptive advantage, it can be considered an
      evolutionary selected process. Multiple developmental and environmental signals
      control senescence, and among them plant hormones are understood to play
      important roles. In particular, the function of cytokinins and ethylene in
      senescence has been studied for decades, but it is only since Arabidopsis
      thaliana was established as a model organism for molecular genetic studies that
      the underlying molecular and biochemical events have begun to be elucidated.
      METHODS: In this review, we summarize the present understanding of the role of
      hormones in the developmental control of leaf senescence in plants and in
      particular highlight recent studies which address its molecular control. RESULTS:
      Important findings which connect hormone action to developmental senescence were
      made in the past few years. For example, it was shown that ethylene activity in
      natural, age-dependent leaf senescence is conferred by the regulatory function of
      EIN2, an ethylene-signaling component, in the control of the transcription factor
      oresara 1 (ORE1), which regulates a large set of senescence-associated genes in
      their expression. ORE1 mRNA abundance is regulated by the microRNA miR164, which
      in aging plants is degraded in an EIN2-dependent manner, and it is interesting
      that another microRNA also governs the hormonal control of senescence. miR319
      regulates mRNA abundance of a class of transcription factors which control the
      expression of LOX2 (lipoxygenase 2), a key enzyme in the JA biosynthetic pathway,
      and thereby regulates JA homeostasis in senescing leaves. CONCLUSION: Reverse and
      forward genetics have facilitated the elucidation of molecular mechanisms
      involved in the control of leaf senescence by phytohormones. Studies initiated on
      the interactions between the different hormonal pathways that control leaf
      senescence should improve our knowledge in the future.

PMID- 24135639
TI  - Course review: the 4th Bob Huffstadt upper and lower limb flap dissection course.
AB  - The Bob Huffstadt course is a 2-day upper and lower limb flap dissection course
      held in Groningen, the Netherlands. The course is in English, with an
      international faculty of senior consultants from the Netherlands, Belgium, and
      United Kingdom. Faculty to participant ratio is 2:1, with 2 participants at each
      dissection table. The course is aimed at trainees in plastic surgery of all
      levels, and a comprehensive DVD is provided before the course, which demonstrates
      dissection of 35 flaps, ensuring those with little experience to have an
      understanding before dissection.This course offered a comprehensive overview with
      plenty of practical application. The course can greatly develop operative and
      theoretical knowledge, while also demonstrating a commitment for those wishing to
      pursue a career in plastic surgery. Longer courses are available; however, the 2
      day course can already provide an excellent introduction for junior trainees.
      There are few flap courses in the United Kingdom and senior trainees may have
      difficulty acquiring a place as they book up well in advance. With reductions in
      operating time, trainees may welcome further experience and development of
      techniques in the dissection room.Most of both days were spent in the dissection
      room, raising flaps and receiving teaching from the faculty. Dissections included
      Foucher, Moberg, Becker, radial forearm, anterolateral thigh, and fibula flaps.
      Dissection specimens were fresh-frozen preparation, and 9 upper limb flaps were
      raised on the first day and 5 lower limb flaps on the second day. The faculty
      provided live demonstrations of perforator dissection, use of the hand-held
      Doppler, and tips and tricks. The last 2 hours of each day were spent with 2
      lectures, including topics from the history of flaps and developments to
      challenging cases and reconstructive options.The course fee was 1000 euros,
      including a 5-course dinner, lunch on both days, and a drinks reception on the
      final evening. I would recommend this course unreservedly to trainees new to
      flaps, or those with greater experience. The course was supportive, friendly, and
      provided an excellent basis to develop reconstructive skills. There is a world
      class faculty who can improve the knowledge and techniques of any trainee in
      attendance. 

PMID- 24135640
TI  - Airway Obstruction and the Unilateral Cleft Lip and Palate Deformity:
      Contributions by the Bony Septum.
AB  - BACKGROUND: Patients with unilateral cleft lip and palate (CLP) deformities
      commonly develop nasal airway obstruction, necessitating septoplasty at the time
      of definitive rhinoplasty. We assessed the contribution of the bony septum to
      airway obstruction using computed tomography (CT) and cone beam CT (CBCT).
      METHODS: A 2-year retrospective review of all subjects with unilateral CLP who
      underwent CBCT imaging (n = 22) and age-matched controls (n = 9) who underwent CT
      imaging was conducted. Control CT scans were used to determine the segment of
      nasal septum comprised almost entirely of bone. The CBCT of the nasal airway was
      assessed using Dolphin software to determine the contribution of the bony septum
      to septal deviation and airway obstruction. RESULTS: The nasal septum posterior
      to the midpoint between anterior and posterior nasal spine is comprised of 96%
      bone. The nasal airway associated with this posterior bony segment was 43.1% (P <
      0.001) larger by volume on the non-cleft side in patients with unilateral CLP.
      The average septal deviation within the posterior bony segment was 5.4 mm,
      accounting for 74.4% of the maximal deviation within the nasal airway. The
      average airway stenosis within the posterior bony nasal airway was 0.45 mm (0-2.2
      mm). CONCLUSIONS: In patients with unilateral CLP, the bony nasal septum can
      demonstrate significant deviation and airway stenosis. Surgeons should consider a
      bony septoplasty in their treatment algorithm in unilateral CLP patients who have
      reached skeletal maturity.

PMID- 24135641
TI  - Fingertip replantation without venous anastomosis: reply.

PMID- 24135642
TI  - Mutational spectrum of Xeroderma pigmentosum group A in Egyptian patients.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease
      characterized by hyperphotosensitivity, DNA repair defects and a predisposition
      to skin cancers. The most frequently occurring type worldwide is the XP group A
      (XPA). There is a close relationship between the clinical features that ranged
      from severe to mild form and the mutational site in XPA gene. The aim of this
      study is to carry out the mutational analysis in Egyptian patients with XP-A.
      This study was carried out on four unrelated Egyptian XP-A families. Clinical
      features were examined and direct sequencing of the coding region of XPA gene was
      performed in patients and their parents. Direct sequencing of the whole coding
      region of the XPA gene revealed the identification of two homozygous nonsense
      mutations: (c.553C >T; p.(Gln185)) and (c.331G>T; p.(Glu111)), which create
      premature, stop codon and a homodeletion (c.374delC: p.Thr125Ilefs 15) that leads
      to frameshift and premature translation termination. We report the identification
      of one novel XPA gene mutation and two known mutations in four unrelated Egyptian
      families with Xermoderma pigmentosum. All explored patients presented severe
      neurological abnormalities and have mutations located in the DNA binding domain.
      This report gives insight on the mutation spectrum of XP-A in Egypt. This would
      provide a valuable tool for early diagnosis of this severe disease.

PMID- 24135643
TI  - The evolutionary analysis reveals domain fusion of proteins with Frizzled-like
      CRD domain.
AB  - Frizzleds (FZDs) are transmembrane receptors in the Wnt signaling pathway and
      they play pivotal roles in developments. The Frizzled-like extracellular Cysteine
      rich domain (Fz-CRD) has been identified in FZDs and other proteins. The origin
      and evolution of these proteins with Fz-CRD is the main interest of this study.
      We found that the Fz-CRD exists in FZD, SFRP, RTK, MFRP, CPZ, CORIN, COL18A1 and
      other proteins. Our systematic analysis revealed that the Fz-CRD domain might
      have originated in protists and then fused with the Frizzled-like seven
      transmembrane domain (7TM) to form the FZD receptors, which duplicated and
      diversified into about 11 members in Vertebrates. The SFRPs and RTKs with the Fz
      CRD were found in sponge and expanded in Vertebrates. Other proteins with Fz-CRD
      may have emerged during Vertebrate evolution through domain fusion. Moreover, we
      found a glycosylation site and several conserved motifs in FZDs, which may be
      related to Wnt interaction. Based on these results, we proposed a model showing
      that the domain fusion and expansion of Fz-CRD genes occurred in Metazoa and
      Vertebrates. Our study may help to pave the way for further research on the
      conservation and diversification of Wnt signaling functions during evolution.

PMID- 24135644
TI  - Association between the - 786T>C 1polymorphism in the promoter region of
      endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: a
      systematic review and meta-analysis.
AB  - BACKGROUND: A variety of studies have evaluated the association between the 
      786T>C polymorphism in the promoter region of endothelial nitric oxide synthase
      (eNOS) and risk of coronary artery disease (CAD). However, the results remain
      conflicting. To better understand the role of eNOS -786T>C polymorphism in CAD
      risk, we conducted a comprehensive systematic review and meta-analysis. METHODS:
      Case-control, cohort or cross-sectional studies evaluating the association
      between eNOS -786T>C polymorphism and CAD risk were searched in electronic
      databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar
      Search (up to January 2013). Overall and subgroup analyses were performed. Odds
      ratio (OR) and 95% confidence interval (CI) were used to evaluate the association
      between eNOS -786T>C polymorphism and CAD risk. Statistical analysis was
      performed with Review Manager 5.0 and STATA12.0. RESULTS: Twenty-four studies
      were analyzed between 6192 CAD cases and 9281 healthy controls. The combined
      results of overall analysis showed significant positive associations between CAD
      risk and eNOS -786T>C polymorphism in dominant model (OR=1.45, 95% CI=1.27-1.65),
      recessive model (OR=1.37, 95% CI=1.20-1.56), homozygote comparison (OR=1.64, 95%
      CI=1.31-2.04), heterozygote comparison (TC vs. TT, OR=1.39, 95% CI=1.23-1.57; CC
      vs. TC, OR=1.20, 95% CI=1.04-1.37) and allele comparison (OR=1.35, 95% CI=1.21
      1.50). On subgroup analysis based on the ethnicity of population (Caucasians,
      Asians and others), significant differences were found in all genetic models for
      Caucasians, similar associations existed in Asians except heterozygote comparison
      (CC vs. TC). However, the associations were only found in dominant model,
      heterozygote comparison (TC vs. TT) and allele comparison for the populations
      named others. CONCLUSIONS: Our investigations demonstrate the significant
      associations between eNOS -786C>T polymorphism and CAD risk, and this
      polymorphism might become an early marker for the risk evaluation of CAD.

PMID- 24135645
TI  - Children's experience of postoperative pain relief: children, parents and nurses
      use various pharmacological and non-pharmacological approaches, particularly
      distraction.

PMID- 24135646
TI  - Excess weight gain in the first 18 months of life is associated with later
      childhood overweight, obesity and greater arterial wall thickness.

PMID- 24135647
TI  - Second trimester hyperemesis gravidarum is associated with increased risk of
      preterm pre-eclampsia, placental abruption and small for gestational age birth.

PMID- 24135648
TI  - Scedosporium prolificans fungaemia in a patient with acute lymphoblastic
      leukaemia.
AB  - Aggressive chemotherapy and immunosuppressive treatment may prolong patients'
      life, but influence the risk of severe, life-threatening infections. Here, we
      report the case of a 21-year-old caucasian female who developed a disseminated
      infection of Scedosporium prolificans after allogenic stem cell transplantation
      performed for treatment of relapsed acute lymphoblastic leukaemia. The pathogen
      was isolated from the blood and identified on the basis of its macroscopic and
      microscopic morphological features. The empirical treatment with amphotericin B
      provided no improvement. However, introduction of intravenous voriconazole
      resulted in amelioration of fever. Unfortunately, the patient died due to
      progression of underlying disease and multiorgan failure. However, this case
      report indicates a possible relevance of voriconazole-based treatment regimens in
      invasive S. prolificans infections. 

PMID- 24135649
TI  - Screening of selected medicinal plants for in vitro antidermatophytic activity.
AB  - Different solvent extracts of leaves of Achyranthes aspera, Aegle marmelos,
      Cleistanthus collinus, Curcuma aromatica and Strychnos nux-vomica were screened
      against dermatophytes viz., Trichophyton mentagrophytes, T. rubrum, Microsporum
      gypseum, M. canis and Epidermophyton floccossum var. nigricans. The mean zones of
      inhibition were between 7.1 and 26.5mm. Minimum inhibitory concentrations (MIC)
      and minimum fungicidal concentrations (MFC) were from 7.81 to 500 and from 15.62
      to 1000MUg/mL respectively. The highest mean zone of inhibition (26.5mm), the
      lowest MIC value (7.81MUg/ml) and the lowest MFC (15.62MUg/ml) were observed in
      ethyl acetate extract of A. aspera against T. rubrum. The standard antifungal
      drug ketoconazole (10MUg/disc) was used as the positive control and mean zones of
      inhibition were from 23 to 29mm. Further separation of active principle from
      ethyl acetate extract of A. aspera is under progress. 

PMID- 24135650
TI  - Good times--bad times: my story regarding acute stroke treatment.

PMID- 24135651
TI  - Methods for site-specific drug conjugation to antibodies.
AB  - Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics
      with the potential to improve therapeutic index over traditional chemotherapy.
      Drugs and linkers have been the current focus of ADC development, in addition to
      antibody and target selection. Recently, however,the importance of conjugate
      homogeneity has been realized. The current methods for drug attachment lead to a
      heterogeneous mixture, and some populations of that mixture have poor in vivo
      performance. New methods for site-specific drug attachment lead to more
      homogeneous conjugates and allow control of the site of drug attachment. These
      subtle improvements can have profound effects on in vivo efficacy and therapeutic
      index. This review examines current methods for site-specific drug conjugation to
      antibodies, and compares in vivo results with their non-specifically conjugated
      counterparts. The apparent improvement in pharmacokinetics and the reduced off
      target toxicity warrant further development of this site-specific modification
      approach for future ADC development.

PMID- 24135652
TI  - Synthesis of 4-nitrophenyl caffeate and its use in assays of caffeoyl esterases.
AB  - We have prepared 4-nitrophenyl caffeate by a combination of standard procedures
      of organic synthesis and enzymatic deacetylation. Based on hydrolysis of 4
      nitrophenyl caffeate, a convenient spectrophotometric assay was developed for
      specific monitoring of caffeoyl esterase. The method is fast and easy to perform,
      and it requires no expensive equipment. Its reliability was tested on eight
      enzyme preparations comprising various combinations of caffeoyl, feruloyl, and
      acetyl esterase as well as protease activities. 

PMID- 24135653
TI  - G-quadruplex-generating polymerase chain reaction for visual colorimetric
      detection of amplicons.
AB  - We have developed a self-reporting polymerase chain reaction (PCR) system for
      visual colorimetric gene detection and distinction of single nucleotide
      polymorphisms (SNPs). Amplification is performed using target-specific primers
      modified with a 5'-end tail that is complementary to a G-quadruplex deoxyribozyme
      forming sequence. At end-point, G-quadruplexes are forced to fold from PCR
      generated duplex DNA and then are used to colorimetrically report the successful
      occurrence of PCR by assaying their peroxidase activity using a chromogenic
      substrate. Furthermore, primer design considerations for the G-quadruplex
      generating PCR system have allowed us to visually distinguish SNPs associated
      with Mycobacterium tuberculosis drug resistance alleles. 

PMID- 24135654
TI  - Radiative decay engineering 7: Tamm state-coupled emission using a hybrid
      plasmonic-photonic structure.
AB  - There is a continuing need to increase the brightness and photostability of
      fluorophores for use in biotechnology, medical diagnostics, and cell imaging. One
      approach developed during the past decade is to use metallic surfaces and
      nanostructures. It is now known that excited state fluorophores display
      interactions with surface plasmons, which can increase the radiative decay rates,
      modify the spatial distribution of emission, and result in directional emission.
      One important example is surface plasmon-coupled emission (SPCE). In this
      phenomenon, the fluorophores at close distances from a thin metal film, typically
      silver, display emission over a small range of angles into the substrate. A
      disadvantage of SPCE is that the emission occurs at large angles relative to the
      surface normal and at angles that are larger than the critical angle for the
      glass substrate. The large angles make it difficult to collect all of the coupled
      emission and have prevented the use of SPCE with high-throughput and/or array
      applications. In the current article, we describe a simple multilayer metal
      dielectric structure that allows excitation with light that is perpendicular
      (normal) to the plane and provides emission within a narrow angular distribution
      that is normal to the plane. This structure consists of a thin silver film on top
      of a multilayer dielectric Bragg grating, with no nanoscale features except for
      the metal or dielectric layer thicknesses. Our structure is designed to support
      optical Tamm states, which are trapped electromagnetic modes between the metal
      film and the underlying Bragg grating. We used simulations with the transfer
      matrix method to understand the optical properties of Tamm states and
      localization of the modes or electric fields in the structure. Tamm states can
      exist with zero in-plane wavevector components and can be created without the use
      of a coupling prism. We show that fluorophores on top of the metal film can
      interact with the Tamm state under the metal film and display Tamm state-coupled
      emission (TSCE). In contrast to SPCE, the Tamm states can display either S or P
      polarization. The TSCE angle is highly sensitive to wavelength, which suggests
      the use of Tamm structures to provide both directional emission and wavelength
      dispersion. Metallic structures can modify fluorophore decay rates but also have
      high losses. Photonic crystals have low losses but may lack the enhanced light
      induced fields near metals. The combination of plasmonic and photonic structures
      offers the opportunity for radiative decay engineering to design new formats for
      clinical testing and other fluorescence-based applications. 

PMID- 24135656
TI  - Fe(III)-resorcylate as a spectrophotometric probe for phospholipid-cation
      interactions.
AB  - A simple spectrophotometric microplate assay that allows quantification of the
      interaction between phospholipids and metal ions or other small cationic
      compounds has been developed. The assay is based on the competition of the
      phospholipids for the Fe(3+) ion in the purple-colored Fe(III)-gamma-resorcylate
      complex and for other cations. To compare the binding affinities of several
      cation-phospholipid interactions, K0.5 values were derived from binding curves
      constructed by determination of the absorbance of the Fe(III)-gamma-resorcylate
      at 490 nm as a function of the cation concentration. The assay was used to
      analyze the binding of lanthanide ions, calcium ions, and amines (hydrochlorides
      of ethanolamine, spermidine, and hexyltrimethylammonium chloride) to small
      unilamellar vesicles (SUVs) and mixed micelles containing anionic lipids such as
      phosphatidic acid and phosphatidyl-p-nitrophenol. The method was evaluated by
      fluorescence measurements with Eu(3+) ions as tracer. Lanthanide ions such as
      La(3+) and Ce(3+) ions showed K0.5 values smaller by one to two orders of
      magnitude compared with Ca(2+) ions. In the presence of increasing amounts of
      detergents such as Triton X-100, the method also reflected transitions from SUVs
      to micelles. The binding capacity for metal ions was higher for phospholipid
      containing micelles than for the corresponding SUVs.

PMID- 24135655
TI  - A modified protein assay from microgram to low nanogram levels in dilute samples.
AB  - In this article, we present a modified and improved protein assay that was
      previously described as "amidoschwarz assay" by Schaffner and Weissmann. Our
      improved protein assay is user-friendly and 30-40 times more sensitive than the
      earlier method. The assay was developed into three formats (macro-, micro-, and
      nanoassay) with trichloroacetic acid (TCA) as protein precipitating agent,
      measuring up to 96 samples. The macro and micro formats of this assay require a
      single reagent staining with amido black of protein dots bound to nitrocellulose
      membrane with lowest protein measurements to 1 and 0.1 MUg, respectively. On the
      other hand, the nanoassay, with combination staining of amido black followed by
      colloidal gold, can extend the detection limit to 2.5 ng of protein. Protein
      concentrations were determined by densitometry and/or spectrophotometry. This
      assay is compatible with many ionic and non-ionic detergents. This improved
      protein assay provides an additional choice to researchers in measuring total
      protein concentration accurately in dilute biological samples as low as 0.125
      MUg/ml prior to their biochemical analysis such as in comparative proteomics.

PMID- 24135657
TI  - A mediator-free glucose biosensor based on glucose oxidase/chitosan/alpha
      zirconium phosphate ternary biocomposite.
AB  - A novel glucose oxidase/chitosan/alpha-zirconium phosphate (GOD/chitosan/alpha
      ZrP) ternary biocomposite was prepared by co-intercalating glucose oxidase (GOD)
      and chitosan into the interlayers of alpha-zirconium phosphate (alpha-ZrP) via a
      delamination-reassembly procedure. The results of X-ray diffraction, infrared
      spectroscopy, circular dichroism, and ultraviolet spectrum characterizations
      indicated not only the layered and hybrid structure of the GOD/chitosan/alpha-ZrP
      ternary biocomposite but also the recovered activity of the intercalated GOD
      improved by the co-intercalated chitosan. By depositing the GOD/chitosan/alpha
      ZrP biocomposite film onto a glassy carbon electrode, the direct electrochemistry
      of the intercalated GOD was achieved with a fast electron transfer rate constant,
      k(s), of 7.48+/-3.52 s(-1). Moreover, this GOD/chitosan/alpha-ZrP biocomposite
      modified electrode exhibited a sensitive response to glucose in the linear range
      of 0.25-8.0 mM (R=0.9994, n=14), with a determination limit of 0.076 mM.

PMID- 24135658
TI  - Patient selection for transcatheter aortic valve replacement.

PMID- 24135659
TI  - Radial versus femoral access.

PMID- 24135660
TI  - Platelet function and genetic testing.

PMID- 24135661
TI  - Intravascular ultrasound versus optical coherence tomography guidance.

PMID- 24135662
TI  - The roles of DNA methylation of NR3C1 and 11beta-HSD2 and exposure to maternal
      mood disorder in utero on newborn neurobehavior.
AB  - Exposure to maternal mood disorder in utero may program infant neurobehavior via
      DNA methylation of the glucocorticoid receptor (NR3C1) and 11beta-hydroxysteroid
      dehydrogenase type 2 ( 11beta-HSD-2), two placental genes that have been
      implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA)
      axis. We tested the relations among prenatal exposure to maternal depression or
      anxiety, methylation of exon 1F of NR3C1 and 11beta-HSD-2, and newborn
      neurobehavior. Controlling for relevant covariates, infants whose mothers
      reported depression during pregnancy and showed greater methylation of placental
      NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than
      infants whose mothers did not report depression. On the other hand, infants whose
      mothers reported anxiety during pregnancy and showed greater methylation of
      placental 11beta-HSD-2 CpG4 were more hypotonic compared with infants of mothers
      who did not report anxiety during pregnancy. Our results support the fetal
      programming hypothesis and suggest that fetal adjustments to cues from the
      intrauterine environment, in this case an environment that could be characterized
      by increased exposure to maternal cortisol, may lead to poor neurodevelopmental
      outcomes. 

PMID- 24135664
TI  - Head injury incidence and mortality in New Zealand over 10 Years.
AB  - BACKGROUND: Although reducing the burden of head injuries is an important focus
      of several injury prevention initiatives, they remain a large proportion of
      injury-related deaths. In New Zealand, trends over time and the socio-economic
      distribution of the cause-specific incidence of head injuries have received
      little attention. METHODS: We analyzed primary hospitalizations (2000-2009) and
      deaths (1999-2008) due to head injury using national mortality and hospital
      discharge databases, specifically exploring variations in age-specific rates by
      major causes over time and by socio-economic deprivation. Population-based
      incidence rate estimates were calculated using census denominators. RESULTS:
      Children aged <5 years and adults aged >=65 years had the highest rates of
      hospitalization and mortality, respectively. Transport-related incidents and
      falls were the leading causes, with most fatal injuries occurring on roads and
      most hospitalized injuries occurring at home. There was a significant increase in
      mortality rates among older adults over the decade, and in most age groups,
      mortality rates increased with increasing levels of socio-economic deprivation.
      CONCLUSIONS: The findings of this review alongside the significant risks of
      premature death and disability reinforce the need to explore policies that
      address the specific causes as well as socio-economic inequalities in their
      distribution in New Zealand.

PMID- 24135663
TI  - Does urticaria risk increase in patients with celiac disease? A large population
      based cohort study.
AB  - BACKGROUND: Case reports and smaller case-control studies suggest an association
      between celiac disease (CD) and urticaria but risk estimates have varied
      considerably across studies and as yet there are no studies on CD and the risk of
      future urticaria. OBJECTIVE: To examine the association between CD and urticaria.
      METHODS: We identified 28,900 patients with biopsy-verified CD (equal to Marsh
      stage 3) and compared them with 143,397 age- and sex-matched controls with
      regards to the risk of urticaria and chronic urticaria (duration >=6 weeks).
      Hazard ratios (HRs) were estimated using a Cox regression model. RESULTS: During
      follow-up, 453 patients with CD and no previous diagnosis of urticaria developed
      urticaria (expected n = 300) and 79 of these 453 had chronic urticaria (expected
      n = 41). The corresponding HRs were 1.51 for any urticaria (95%CI = 1.36-1.68)
      and 1.92 for chronic urticaria (95%CI = 1.48-2.48). The absolute risk for
      urticaria in CD was 140/100,000 person-years (excess risk = 47/100,000 person
      years). Corresponding figures for chronic urticaria were 24/100,000 person-years
      and 12/100,000 person-years. Patients with CD were also at increased risk of
      having both urticaria (odds ratio, OR = 1.31; 95%CI = 1.12-1.52) and chronic
      urticaria (OR = 1.54; 95%CI = 1.08-2.18) prior to the CD diagnosis. CONCLUSION:
      This study suggests that CD is associated with urticaria, especially chronic
      urticaria.

PMID- 24135665
TI  - What's new in Shock? November 2013.

PMID- 24135666
TI  - Diagnosis of DRESS (drug reaction with eosinophilia and systemic symptoms) in the
      intensive care unit: essential but challenging.

PMID- 24135667
TI  - Evolution of the indigenous microbiota in modified atmosphere packaged Atlantic
      horse mackerel (Trachurus trachurus) identified by conventional and molecular
      methods.
AB  - A combination of conventional methods and genetic identification (PCR sequencing)
      was used to study the dynamics of the bacterial population during the spoilage of
      modified atmosphere packaged (MAP) Atlantic horse mackerel (Trachurus trachurus)
      fillets. The cultivable microflora in Atlantic horse mackerel samples packaged in
      a modified atmosphere (48% CO2, 50% N2 and 2% O2) at refrigeration temperature (6
      degrees C) was measured on days 1, 5 and 7 using non-selective (Long and Hammer
      agar) and selective media (Kligler's iron agar, STAA and MRS). The microflora was
      genetically characterised using partial amplification of 16S rRNA gene sequences
      from 309 bacterial isolates obtained from Long and Hammer agar. At the end of the
      shelf life (5 days), the total viable counts (TVC) on Long and Hammer agar were
      not significantly different to the LAB counts on MRS agar (p>0.05). The molecular
      approach showed that Photobacterium, Arthrobacter, Chryseobacterium and
      Pseudoclavibacter (44.5% of total) dominated the microbial composition of the
      fish at the beginning of storage. However, Serratia, Shewanella and Yersinia
      dominated at the late spoilage stages (over 57.2% of the total). Carnobacterium
      was the most important species of the lactic acid bacteria (LAB) and was
      identified at the beginning and end of the storage period. Vibrio spp. was only
      found at the end of the shelf life. This research demonstrates that the microbial
      biodiversity in MAP Atlantic horse mackerel is enormous and the dominant species
      change over the storage time. The results presented here on the dominant
      communities in fish products will make it possible to accurately select the best
      preservation practices.

PMID- 24135668
TI  - A predictive model for assessment of decontamination effects of lactic acid and
      chitosan used in combination on Vibrio parahaemolyticus in shrimps.
AB  - Vibrio parahaemolyticus is a major causative agent of human gastroenteritis in
      seafood products including shrimps. Lactic acid and chitosan are natural
      antimicrobials for food decontamination in the washing process of seafood. In
      this research, a 4-factor response surface model based on the Box-Behnken
      experimental design was developed to evaluate the effects of lactic acid (1%, 2%,
      and 3%, v/v), chitosan (0.4%, 1%, and 1.6%, w/v), rotational rate (90, 110, and
      130 rpm) and washing time (10, 20, and 30 min) on reduction of V.
      parahaemolyticus inoculated in raw shrimps. These treatments achieved 2.2 to 4.3
      log10 CFU/g reduction of V. parahaemolyticus in shrimps. Stepwise stratification
      led to a simplified model that has a satisfactory performance as evidenced by
      statistical indices (R(2) = 0.92; p<0.0001; RMSE = 0.196) and external validation
      parameters [bias factor (Bf) = 1.01; accuracy factor (Af) = 1.05]. The model
      generated an optimum treatment combination (3% lactic acid, 1.6% chitosan, and
      rotational rate at 110 rpm) that could achieve greatest bacterial reduction of
      4.5 log10 CFU/g. Among the four factors, lactic acid and chitosan were the major
      contributors for bacterial decontamination. Analysis of variances showed a
      significant interactive inactivation effect (p<0.05) from combined use of lactic
      acid and chitosan. The treatments did not have adverse effects on the quality
      attributes such as color and pH of the shrimps.

PMID- 24135669
TI  - Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory
      peptides produced by Bifidobacterium bifidum MF 20/5.
AB  - In previous research, we have demonstrated that Bifidobacterium bifidum MF 20/5
      fermented milk possessed stronger angiotensin converting enzyme (ACE) inhibitory
      activity than other lactic acid bacteria, including Lactobacillus helveticus DSM
      13137, which produces the hypotensive casokinins Ile-Pro-Pro (IPP) and Val-Pro
      Pro (VPP). The aim of this study is to investigate the ACE-inhibitory peptides
      released in B. bifidum MF 20/5 fermented milk. The novel ACE-inhibitory peptide
      LVYPFP (IC50 = 132 MUM) is reported here for the first time. Additionally, other
      bioactive peptides such as the ACE-inhibitor LPLP (IC50 = 703 MUM), and the
      antioxidant VLPVPQK were identified. Moreover, the peptide and amino acid
      profiles, the ACE-inhibitory activity (ACEi), pH, and degree of hydrolysis of the
      fermented milk were determined and compared with those obtained in milk fermented
      by L. helveticus DSM 13137. The sequences of the major bioactive peptides present
      in fermented milk of B. bifidum and L. helveticus were identified and quantified.
      B. bifidum released a larger amount of peptides than L. helveticus but no IPP or
      VPP were detected in B. bifidum fermented milk. Also the lactotripeptide
      concentrations and ACEi were higher in L. helveticus fermented milk when the pH
      was maintained at 4.6. This may represent a technical advantage for B. bifidum
      that reduces the pH at a slow enough rate to facilitate the peptide generation
      without the need for pH control. Thus these findings show the potential for the
      use of this probiotic strain to produce fermented milk with a wider range of
      health benefits including reduction of blood pressure.

PMID- 24135670
TI  - The influence of temperature, pH, and water immersion on the high hydrostatic
      pressure inactivation of GI.1 and GII.4 human noroviruses.
AB  - Detection of human norovirus (HuNoV) usually relies on molecular biology
      techniques, such as qRT-PCR. Since histo-blood group antigens (HBGAs) are the
      functional receptors for HuNoV, HuNoV can bind to porcine gastric mucin (PGM),
      which contains HBGA-like antigens. In this study, PGM-conjugated magnetic beads
      were used to collect and quantify potentially infectious HuNoV strains GI.1 and
      GII.4 treated by high hydrostatic pressure (HHP). Both GI.1 and GII.4 strains
      used in this study showed increasing pressure sensitivity as judged by loss of
      PGM binding with decreasing temperature over a range of 1 to 35  degrees C. Both
      GI.1 and GII.4 were more resistant to pressure at pH4 than at neutral pH. Because
      GI.1 was significantly more resistant to pressure than GII.4, it was used to
      evaluate HuNoV pressure inactivation in blueberries. GI.1 on dry blueberries was
      very resistant to pressure while immersion of blueberries in water during
      pressure treatments substantially enhanced the inactivation. For example, a 2 min
      600 MPa treatment of dry blueberries at 1 and 21  degrees C resulted in <1-log
      reductions while a 2.7-log reduction of GI.1 was achieved by a treatment at 500
      MPa for 2 min at 1  degrees C when blueberries were immersed in water. In total,
      this novel study provides unique information for designing pressure processing
      parameters (pressure, temperature, and time) and product formulations (such as
      pH) to inactivate HuNoV in high-risk foods such as berries.

PMID- 24135671
TI  - Review: Utilization of antagonistic yeasts to manage postharvest fungal diseases
      of fruit.
AB  - Significant losses in harvested fruit can be directly attributable to decay
      fungi. Some of these pathogenic fungi are also the source of mycotoxins that are
      harmful to humans. Biological control of postharvest decay of fruits, vegetables
      and grains using antagonistic yeasts has been explored as one of several
      promising alternatives to chemical fungicides, the use of which is facing
      increasingly more stringent regulation. Yeast species have been isolated over the
      past two decades from a variety of sources, including fruit surfaces, the
      phyllosphere, soil and sea water, and their potential as postharvest biocontrol
      agents has been investigated. Several mechanisms have been proposed as
      responsible for their antagonistic activity, including competition for nutrients
      and space, parasitism of the pathogen, secretion of antifungal compounds,
      induction of host resistance, biofilm formation, and most recently, the
      involvement of reactive oxygen species (ROS) in defense response. It has been
      recognized that a biocontrol system is composed of a three-way interaction
      between the host (commodity), the pathogen and the yeast, all of which are
      affected by environmental factors. Efficacy and consistent performance in
      controlling postharvest diseases are the hurdles that must be overcome if the use
      of yeast biocontrol agents and other alternatives are to be widely used
      commercially. Therefore, attempts have been made to combine alternative
      treatments in order improve their overall performance. The current review
      provides a brief overview of the topic of the use of yeasts as postharvest
      biocontrol agents and includes information on the sources from which yeast
      antagonists have been isolated, their mode of action, and abiotic stress
      resistance in yeast as it relates to biocontrol performance. Areas in need of
      future research are also highlighted. 

PMID- 24135672
TI  - Organic acid based sanitizers and free chlorine to improve the microbial quality
      and shelf-life of sugar snaps.
AB  - A screening in a sugar snap packaging company showed a converged build-up of
      aerobic psychrotrophic plate count (APC) (ca. 6.5 log CFU/100mL), yeasts and
      molds (Y&M), and lactic acid bacteria (LAB) (both ca. 4.5 log CFU/100mL) in the
      wash water in the absence of water sanitizer, and a low build-up of chemical
      oxygen demand (30 +/- 5 mg O2/L) and turbidity (5.2 +/- 1.1 NTU). Decontamination
      experiments were performed in the lab with Purac FCC 80(r) (80% L(+) lactic
      acid), two other commercial water sanitizers based on organic acids (NATRApHASe
      ABAV(r), and NATRApHASe-FVS(r)) and chlorine to evaluate their performance in
      reduction of the sugar snap microbial load as well as their functionality as
      disinfectant of the wash water to avoid cross-contamination. An additional 1 log
      reduction of APC on the sugar snaps was achieved with lactic acid in the range
      0.8 to 1.6%, ABAV 0.5%, and free chlorine 200mg/L when compared to a water wash,
      while no significant difference in the numbers of Y&M was obtained when washing
      in sanitizer compared to water. There was no significant influence of the studied
      concentration and contact time on decontamination efficiency. Treatment with
      lactic acid 0.8% resulted in a lower APC contamination on the sugar snaps than on
      the untreated and water washed samples for 10 days. Chlorine 200mg/L was the only
      treatment able to maintain the Y&M load lower than the untreated samples
      throughout the entire storage duration. The use of water sanitizers could not
      extend the sensorial shelf-life. Microbial loads were not indicative/predictive
      of visual microbial spoilage (shelf-life limiting factor), whereas maturity and
      amount of damage at the calyx end of the pods were. The APC wash water
      contamination (5.2 log CFU/100mL) was reduced significantly by chlorine 20 to
      200mg/L (to 1.4 log CFU/100mL), ABAV 0.5 to 1.5% (to 2.7 log CFU/100mL), FVS 0.5%
      (to 2.7 log CFU/100mL) and lactic acid 0.8 to 1.6% (to 3.4 log CFU/100mL). Only
      the use of chlorine enabled the reduction of the Y&M wash water contamination
      significantly (from 3.4 to 1.4 log CFU/100mL). The low physicochemical build-up
      of the sugar snap wash water during the industrial washing process makes free
      chlorine attractive as a water disinfectant to prevent bacterial and fungal cross
      contamination, whereas the sanitizers based on organic acids are not, due to
      their weak water disinfection efficiency.

PMID- 24135673
TI  - Enhancement of gamma-aminobutyric acid (GABA) in Nham (Thai fermented pork
      sausage) using starter cultures of Lactobacillus namurensis NH2 and Pediococcus
      pentosaceus HN8.
AB  - The aim was to produce Nham that was enriched with gamma-aminobutyric acid
      (GABA); therefore two GABA producing lactic acid bacteria (Pediococcus
      pentosaceus HN8 and Lactobacillus namurensis NH2) were used as starter cultures.
      By using the central composite design (CCD) we showed that addition of 0.5%
      monosodium glutamate (MSG) together with an inoculum size of roughly 6logCFU/g of
      each of the two strains produced a maximal amounts of GABA (4051 mg/kg) in the
      'GABA Nham' product. This was higher than any current popular commercial Nham
      product by roughly 8 times. 'GABA Nham' with the additions of both starters and
      MSG (TSM) supported maximum populations of lactic acid bacteria (LAB) with a
      minimum of yeasts and no staphylococci or molds when compared to the controls
      that had no addition of any starters or MSG (TNN), or only the addition of MSG
      (TNM), or with only the starter (TSN). Based on proximate analysis among the Nham
      sets, 'GABA Nham' was low in fat, carbohydrate and energy although its texture
      and color were slightly different from the control (TNN). However, sensory
      evaluations of 'GABA Nham' were more acceptable than the controls and commercial
      Nham products for all tested parameters. Hence, a unique novel 'GABA Nham'
      fermented pork sausage was successfully developed.

PMID- 24135674
TI  - Tracing enteric viruses in the European berry fruit supply chain.
AB  - In recent years, numerous foodborne outbreaks due to consumption of berry fruit
      contaminated by human enteric viruses have been reported. This European
      multinational study investigated possible contamination routes by monitoring the
      entire food chain for a panel of human and animal enteric viruses. A total of 785
      samples were collected throughout the food production chain of four European
      countries (Czech Republic, Finland, Poland and Serbia) during two growing
      seasons. Samples were taken during the production phase, the processing phase,
      and at point-of-sale. Samples included irrigation water, animal faeces, food
      handlers' hand swabs, swabs from toilets on farms, from conveyor belts at
      processing plants, and of raspberries or strawberries at points-of-sale; all were
      subjected to virus analysis. The samples were analysed by real-time (reverse
      transcription, RT)-PCR, primarily for human adenoviruses (hAdV) to demonstrate
      that a route of contamination existed from infected persons to the food supply
      chain. The analyses also included testing for the presence of selected human
      (norovirus, NoV GI, NoV GII and hepatitis A virus, HAV), animal (porcine
      adenovirus, pAdV and bovine polyomavirus, bPyV) and zoonotic (hepatitis E virus,
      HEV) viruses. At berry production, hAdV was found in 9.5%, 5.8% and 9.1% of
      samples of irrigation water, food handlers' hands and toilets, respectively. At
      the processing plants, hAdV was detected in one (2.0%) swab from a food handler's
      hand. At point-of-sale, the prevalence of hAdV in fresh raspberries, frozen
      raspberries and fresh strawberries, was 0.7%, 3.2% and 2.0%, respectively. Of the
      human pathogenic viruses, NoV GII was detected in two (3.6%) water samples at
      berry production, but no HAV was detected in any of the samples. HEV-contaminated
      frozen raspberries were found once (2.6%). Animal faecal contamination was
      evidenced by positive pAdV and bPyV assay results. At berry production, one water
      sample contained both viruses, and at point-of-sale 5.7% and 1.3% of fresh and
      frozen berries tested positive for pAdV. At berry production hAdV was found both
      in irrigation water and on food handler's hands, which indicated that these may
      be important vehicles by which human pathogenic viruses enter the berry fruit
      chain. Moreover, both zoonotic and animal enteric viruses could be detected on
      the end products. This study gives insight into viral sources and transmission
      routes and emphasizes the necessity for thorough compliance with good
      agricultural and hygienic practice at the farms to help protect the public from
      viral infections. 

PMID- 24135675
TI  - Characteristics of Escherichia coli from raw vegetables at a retail market in the
      Czech Republic.
AB  - A large epidemic caused by shigatoxigenic Escherichia coli (E. coli) in spring
      2011 in Germany resulted in reduction of trust in the health safety of raw
      vegetables and sprouted seeds. This study focused on the detection and
      characterization of E. coli in raw vegetables and sprouted seeds sold in the
      Czech Republic. Out of 91 samples, 24 (26.4%) were positive for the presence of
      E. coli. Resistance to antimicrobial agents was determined by the disk diffusion
      method and E-test. Polymerase chain reaction was used for the detection of
      selected genes encoding virulence--eaeA, hly, stx1, and stx2 and genes encoding
      resistance to tetracycline--tet(A), tet(B), tet(C), and tet(G) and to beta
      lactams--blaTEM, blaSHV, and blaCTX. The blaTEM gene was detected in two
      isolates, the tet(B) gene in three and tet(A) in one isolate. No hly, stx1, or
      stx2 genes were present, but the eaeA gene was found in three (11.1%) isolates
      from imported vegetables. These isolates can be considered as potentially
      enteropathogenic. Results of this study show that raw vegetables and sprouted
      seeds sold in the retail market can represent a potential risk for consumers.

PMID- 24135676
TI  - Comparative proteomic analysis of Listeria monocytogenes exposed to enterocin AS
      48 in planktonic and sessile states.
AB  - Enterocin AS-48 is a cyclic peptide of great interest for application in food
      preservation and sanitation. In the present study, the proteome response of
      Listeria monocytogenes to purified enterocin AS-48 was studied under two
      different conditions: planktonic cells and sessile cells grown on polystyrene
      plates. Ten different proteins were differentially expressed in planktonic L.
      monocytogenes cells treated with 0.1 MUg/ml enterocin AS-48 compared to the
      untreated controls. Overexpressed proteins were related to stress response (DnaK)
      or carbohydrate transport and metabolism, while underexpressed and unexpressed
      proteins were related to metabolism (such as glyceraldehyde-3-phosphate
      dehydrogenase, pyruvate oxidase, glutamate dehydrogenase or glutamate
      decarboxylase) or stress (GroEL). In the sessile state, L. monocytogenes cells
      tolerated up to 10 MUg/ml bacteriocin, and the treated biofilm cells
      overexpressed a set of 11 proteins, some of which could be related to stress
      response (DnaK, GroEL), protein synthesis and carbohydrate metabolism, while
      glyceraldehyde-3-phosphate dehydrogenase was the only unexpressed protein. Some
      of the overexpressed proteins (such as elongation factor Tu and GroEL) could also
      be implicated in cell adhesion. These results suggest different cell responses of
      L. monocytogenes to enterocin AS-48 in the planktonic and in the sessile state,
      including stress response and cell metabolism proteins. While in the planktonic
      state the bacterium may tend to compensate for the cytoplasmic cell permeability
      changes induced by AS-48 by reinforcing carbohydrate transport and metabolism,
      sessile cells seem to respond by shifting carbohydrate metabolism and reinforcing
      protein synthesis. Stress response proteins also seem to be important in the
      response to AS-48, but the stress response seems to be different in planktonic
      and in sessile cells.

PMID- 24135677
TI  - Occurrence of extended-spectrum beta-lactamases among isolates of Salmonella
      enterica subsp. enterica from food-producing animals and food products, in
      Portugal.
AB  - A total of 1120 Salmonella spp. isolates, recovered from poultry, swine and food
      products of animal origin (bovine, swine and poultry) over the period of 2009
      2011, were investigated in order to determine their serotype, susceptibility to a
      panel of eleven antimicrobials (A, ampicillin; Ct, cefotaxime; Cp, ciprofloxacin;
      Tm, trimethoprim; Su, sulfamethoxazole; C, chloramphenicol; S, streptomycin; G,
      gentamicin; T, tetracycline; NA, nalidixic acid; Fl, florfenicol), and the
      presence of resistance determinants of extended-spectrum cephalosporins. Overall,
      Salmonella Enteritidis was the most common serotype in all three animal species.
      In 618 isolates of poultry, 32.8% comprised S. Enteritidis, 18.3% Salmonella
      Havana and 16.5% Salmonella Mbandaka; in 101 isolates of pigs, 21.8% comprised
      Salmonella Rissen and Salmonella Typhimurium, 10.9% Salmonella Derby and
      Salmonella London. Salmonella I 4,[5],12:i:- was the most common serotype
      recovered from pork and beef food products comprising 32.6% and 30% of isolates
      respectively, followed by S. Rissen (26% and 24%) and S. Typhimurium (18.2% and
      19%), respectively. In poultry products, S. Enteritidis was the most frequent
      serotype (62.7%), followed by S. Mbandaka (10.2%) and S. Derby (8.5%).
      Susceptibility profiles differed according to the origin of the isolates. Five
      multidrug resistant isolates (0.45%) were further characterized as extended
      spectrum beta-lactamase (ESBL) producers. Polymerase chain reaction and
      sequencing of the amplicons confirmed the presence of bla(CTX-M-1) (n = 2),
      bla(CTX-M-14) (n = 1), bla(CTX-M-15) (n = 1) and bla(CTX-M-32) (n = 1); bla(SHV
      12) and bla(TEM-1) genes were also detected in two isolates of S. I 4,[5],12:i:-.
      Four isolates, two S. Havana and two S. I 4,[5],12:i:-, carried class 1 integrons
      and in three, two S. I 4,[5],12:i:- and one S. Havana, ISEcp1 was identified
      associated to bla(CTX-M-1), bla(CTX-M-32) and bla(CTX-M-14) genes. Additionally,
      in one S. I 4,[5],12:i:- isolate, orf477 was identified linked to bla(CTX-M-32).
      No plasmid mediated quinolone resistance-encoding genes were detected. Here, we
      report for the first time the presence of bla(CTX-M) genes in Salmonella enterica
      subsp enterica isolates recovered from poultry and food products of swine origin,
      in Portugal.

PMID- 24135678
TI  - Uterine adenosarcomas: a dual-institution update on staging, prognosis and
      survival.
AB  - OBJECTIVE: Uterine adenosarcomas (AS) are rare tumors thought to have a favorable
      prognosis. The aim of this study was to evaluate clinicopathological
      characteristics and treatment outcome in women with uterine AS. METHODS: Patients
      with uterine AS were identified from the institutional databases at two regional
      cancer centers, Princess Margaret Hospital, Toronto and Vancouver General
      Hospital. All cases underwent specialist pathological review and were re-staged
      according to FIGO criteria (2009). Patient demographics, treatment data and
      outcomes were evaluated. RESULTS: Between 1984 and 2010, 64 patients with
      confirmed AS were identified: 30 exhibited sarcomatous overgrowth (AS+SO). 47
      patients presented with stage I disease: 27 IA and 18 IB. 57 of the 58 patients
      with known surgical management underwent hysterectomy: 55 having bilateral
      salpingo-oophorectomy, 12 having lymph node dissection. 14 patients received
      adjuvant treatment: 10 radiotherapy, 3 chemotherapy and 1 both. Sixteen of the 45
      patients (35.6%) with follow-up recurred; median time to recurrence 21.2 months,
      range 2.1-87.8 months. Recurrence was associated with myometrial invasion
      (p=0.05). Two of the 10 women (20%) with AS+SO receiving adjuvant treatment
      recurred compared to 9 of the 14 (64%) who did not. One of the 5 women (20%) with
      stage IB disease who received adjuvant treatment recurred (20%) compared to 6 of
      the 7 (85.6%) who did not. CONCLUSIONS: Long term surveillance is required given
      the variable time to recurrence. For those with AS+SO and myometrial invasion
      adjuvant treatment should be considered and further investigation of adjuvant
      strategies is warranted.

PMID- 24135679
TI  - Early stage papillary serous or clear cell carcinoma confined to or involving an
      endometrial polyp: outcomes with and without adjuvant therapy.
AB  - OBJECTIVE: To investigate clinical outcomes of stage IA uterine papillary serous
      (UPSC) and clear cell carcinoma (CC) arising from or associated with a polyp.
      METHODS: From 1995 to 2011, we identified 51 cases of stage IA UPSC (67%), CC
      (8%) or mixed histology (26%) endometrial cancer. Of these, 32 had disease
      confined to polyp (seven with no residual disease after hysterectomy), 14 had
      surface spread, 1 had myometrial invasion (MMI) and 4 had both. The majority of
      patients did not receive adjuvant therapy (80%). Patients given adjuvant
      treatment (either platinum-based chemotherapy alone, radiation alone, or a
      combination of the two) had incomplete staging or abnormal cytology. RESULTS: At
      mean follow-up of 58.3 months, only 4 patients had progressed, via pelvic
      adenopathy, carcinomatosis or both. There were no vaginal cuff recurrences.
      Kaplan-Meier 5 year estimates were pelvic control of 92.1%, disease-free survival
      93% and OS 80.6%. Only 9% (3/32) of cases confined to polyp progressed. One
      responded to salvage chemoradiation, but two died despite salvage. Only 5% (1/19)
      of cases with surface and MMI progressed. On univariate analysis, only MMI and
      abnormal/positive cytology were significantly associated with increased pelvic
      recurrence (MMI p=0.0059, cytology p=0.0036) and worse DFS (MMI p=0.0018,
      cytology p=0.0054). Two patients given adjuvant treatment developed new
      gynecologic malignancies. CONCLUSION: In our study, patients with limited UPSC/CC
      disease involving a polyp who have complete workup did well without adjuvant
      therapy, with recurrence rates similar to UPSC/CC stage IA disease. Late and
      extensive pelvic relapses may occur in the few who do relapse.

PMID- 24135680
TI  - Spinal anaesthesia in a patient with post-spine surgery dural ectasia.
AB  - Dural sac ectasia is a very infrequent anatomical abnormality, usually caused by
      connective tissue diseases, as Marfan syndrome. Very few cases have been
      described being a consequence of a previous spine surgical procedure. We describe
      the case of an elderly patient who should be operated on twice due to sub
      occlusive colon disease. Surgery was performed under spinal anaesthesia. A dural
      sac ectasia was suspected after the first procedure and the abdominal X-ray was
      reviewed. The characteristics of the anatomical alteration and the course of both
      anaesthetic procedures were described. X-ray and CT images were provided.

PMID- 24135682
TI  - Annular elastolytic giant cell granuloma associated to late-onset X-linked
      dominant protoporphyria.
AB  - X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the
      synthesis of the heme group due to an increase in delta-aminolaevulinate synthase
      2 (ALAS2) enzyme activity. Moreover, annular elastolytic giant-cell granuloma
      (AEGCG) is a rare reactive granulomatous dermatosis, usually associated with
      actinic damage. An 86-year-old man presented with edematous-erythematous lesions
      in photoexposed areas of the face and on the dorsum of both hands. Protoporphyrin
      levels in serum and feces were significantly elevated and a heterozygous
      frameshift mutation in the exon 11 of the ALAS2 gene: c.1706-1709del
      (p.Glu569GlyfsX24) was identified. Concomitantly, we observed an annular plaque
      with raised borders on the back of his right hand, clinically and histologically
      compatible with a diagnosis of AEGCG. Skin lesions disappeared only upon use of a
      physical sunscreen. We report two rare photodermatoses in an elderly patient and
      discuss the significance of dermal elastic fiber damage induced by the XLDPP as a
      main triggering factor of AEGCG.

PMID- 24135681
TI  - Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic
      regions.
AB  - Enhancers are cis-acting elements capable of regulating transcription in a
      distance and orientation-independent manner. A subset of enhancers are occupied
      by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs
      termed eRNAs. We thoroughly investigated the association between eRNA
      productivity and various chromatin marks and transcriptional regulators in mouse
      embryonic stem cells (ESCs) through an integrative approach. We found that eRNA
      producing enhancers exhibited elevated levels of the active mark H3K27Ac,
      decreased DNA methylation, and enrichment for the DNA hydroxylase Tet1. Many eRNA
      producing enhancers have recently been characterized as "super-enhancers,"
      suggesting an important role in the maintenance of pluripotency. Using
      experimental methods, we focally investigated a well-characterized enhancer
      linked to the Nanog locus and confirmed its exclusive eRNA productivity in ESCs.
      We further demonstrate that the binding of Sall4 and Tet family proteins were
      required for eRNA productivity at this locus. Collectively, we demonstrate that
      Tet1 binding and DNA hypomethylation are hallmarks of eRNA production. 

PMID- 24135683
TI  - Nanosuspension improves tretinoin photostability and delivery to the skin.
AB  - The aims of this work were to improve cutaneous targeting and photostability of
      tretinoin by using nanosuspension formulation. Tretinoin is a drug widely used in
      the topical treatment of various dermatological diseases. The tretinoin
      nanosuspension was prepared by precipitation method and then characterized by
      photo correlation spectroscopy for mean size and size distribution, and by
      transmission electron microscopy for morphological studies. An oil in water
      tretinoin nanoemulsion was also prepared and used as a control. Dermal and
      transdermal delivery of both tretinoin nanosuspension and nanoemulsion were
      tested in vitro by using Franz diffusion cells and newborn pig skin.
      Photodegradation studies were carried out by UV irradiation (1h, lambda=366 nm)
      of the tretinoin nanosuspension in comparison with the nanoemulsion and a
      methanolic solution of the drug. During 8h percutaneous experiments, the
      nanosuspesion was able to localize the drug into the pig skin with a very low
      transdermal drug delivery, whereas the nanoemulsion greatly improved drug
      permeation. UV irradiation of the nanosuspension showed a great improvement of
      tretinoin stability in comparison with both controls. Overall results show that
      nanosuspension might be a useful formulation for improving tretinoin dermal
      delivery and stability.

PMID- 24135684
TI  - Primary cardiac sarcomas: a retrospective study of the French Sarcoma Group.
AB  - INTRODUCTION: Primary cardiac sarcomas (PCS) are rare tumours of dismal
      prognosis. METHODS: Data of 124 patients with PCS referred to institutions of the
      French Sarcoma Group (FSG) from 1977 and 2010 were reviewed. RESULTS: Median age
      was 48.8years. PCS were poorly-differentiated sarcomas (N=45, 36.3%),
      angiosarcomas (N=40, 32.3%), leiomyosarcomas (N=16, 12.9%) and others (N=23,
      18.6%). At diagnosis, 100 patients (80.6%) were localised and 24 (19.4%)
      metastatic. Tumours were located in the right (N=47, 38.8%), left atrial cavities
      (N=45, 37.2%) or encompassed several locations in nine cases (7.4%). Surgery was
      performed in 81 cases (65.3%). Heart transplant was performed in five patients.
      Radiotherapy adjuvant (N=18, 14.5%) or alone (N=6, 4.8%) was performed in non
      metastatic patients only (N=24, 19.4%). With a median follow-up of 51.2months,
      median overall survival (OS) was 17.2months for the entire cohort, 38.8months
      after complete resection versus 18.2 after incomplete resection and 11.2months in
      non-resected patients. Radiotherapy was associated with improved progression-free
      survival (PFS) on multivariate analysis. Chemotherapy was significantly
      associated with better OS only in non-operated patients but not in operated
      patients. In non-metastatic patients, surgery (hazard ratio [HR]=0.42, p<0.001),
      male gender (HR=0.56, p=.032) was associated with better OS and surgery (HR=0.61;
      p=.076), radiotherapy (HR=0.43; p=.004) and chemotherapy (HR=0.30, p=.003)
      improved PFS. CONCLUSION: Only surgical resection is associated with a
      perspective of prolonged survival. Chemotherapy is associated with a better
      outcome in non-resected patients.

PMID- 24135685
TI  - The NF-kappaB pathway is rarely spontaneously activated in mantle cell lymphoma
      (MCL) cell lines and patient's samples.
AB  - In this study, we investigated the role of NF-kappaB (canonical and alternative
      pathways) in the survival or proliferation of mantle cell lymphoma (MCL) cell
      lines. P50/p65 complexes were detectable by EMSA assays in 4/5 cell lines. Stable
      expression of a dominant-negative form of IkBa had no effect on proliferation nor
      on apoptosis in EBV-negative cell lines. Three out of 4 of the cell lines tested
      exhibited Phospho-p65 (Ser(536)). The alternative NF-kappaB pathway was not
      activated in 4/5 cell lines tested. Patient samples were also studied by Western
      blot, EMSA and Immunohistochemistry (IHC). No p50/p65 complexes were detected in
      cells freshly collected from 7 patients, but 1/7 cells exhibited Phospho-p65
      (Ser(536)). We investigated immunohistochemically, the expression of NF-kappaB in
      86 patients enrolled in two multicentre prospective trials. Patients with MCL
      exhibiting negative or positive cytoplasmic expression of NF-kappaB had a median
      overall survival of 35.7months compared to 22.4months for patients with nuclear
      NF-kappaB expression (p=0.0193). All these data suggest that NF-kappaB does not
      play a key role in proliferation and apoptotic processes in MCL cell lines. In
      patient samples, the presence of p65 in the nucleus reflecting NF-kappaB
      activation is rare but associated with a poor outcome. 

PMID- 24135686
TI  - Models predicting non-sentinel node involvement also predict for regional
      recurrence in breast cancer patients without axillary treatment.
AB  - BACKGROUND: Non-SN prediction models are frequently used in clinical decision
      making to identify patients that may not need axillary treatment, but these
      models still need to be validated by follow-up data. Our purpose was the
      validation of non-sentinel node (SN) prediction models in predicting regional
      recurrences in patients without axillary treatment. METHODS: We followed a cohort
      of 486 women with favorable primary tumor characteristics and pN0(i+)(sn) or
      pN1mi(sn) for median 4.5 years. None of the patients underwent axillary
      treatment. Based on four published non-SN prediction models, the threshold
      allowing separation into low versus high-risk on non-SN involvement was set at
      10%. RESULTS: Overall 5-year regional recurrence rate was 3.0% (SE, +/-0.1%).
      Using the Tenon scoring system, 438 low-risk patients had a 5-year regional
      recurrence rate of 2.3% (+/-0.8%), and 48 high-risk patients a recurrence rate of
      10.1% (+/-0.4%). The MSKCC nomogram identified 300 low-risk patients with a
      recurrence rate of 2.8% (+/-1.1%), versus 166 high-risk patients with a rate of
      3.4% (+/-0.5%) (20 patients not assessable). The Stanford nomogram identified 21
      high-risk patients without recurrence, and 465 low-risk patients with a 3.2% (+/
      0.9%) recurrence rate. A Dutch model discriminated between 384 low-risk patients
      with a recurrence rate of 2.2% (+/-0.8%) and 102 high-risk patients with a rate
      of 6.3% (+/-2.9%). CONCLUSION: The Tenon scoring system outperformed the other
      models as it identified the largest subgroup of patients with low recurrence
      rate. In patients resembling our cohort we would recommend axillary treatment if
      they had a Tenon score above 3.5.

PMID- 24135687
TI  - The employment of nurses in publicly funded substance abuse treatment programs.
AB  - Little is known about the organizational and environmental factors associated
      with the employment of nurses in substance abuse treatment programs. Using data
      collected from the administrators of 250 publicly funded substance abuse
      treatment programs, this study examined the organizational and environmental
      correlates of nurse employment in these settings. Negative binomial regression
      models indicated that the number of nurses employed by treatment programs was
      positively associated with government ownership, location within a healthcare
      setting, and the availability of detoxification services. Outpatient-only
      programs employed fewer nurses than programs with inpatient/residential services.
      Two environmental factors were associated with nurse employment. Programs that
      more strongly endorsed a scale of financial barriers employed significantly fewer
      nurses, whereas programs indicating that funding from state contracts could be
      used to pay for healthcare providers employed significantly more nurses. These
      findings suggest that organizational decisions about employing nurses may reflect
      both the characteristics of the program and the funding environment. Future
      research should continue to examine the employment of nurses in substance abuse
      treatment settings, particularly given the shifting environment due to the
      implementation of healthcare reform. 

PMID- 24135688
TI  - Single-stage nipple-areolar complex reconstruction technique, outcomes, and
      patient satisfaction.
AB  - INTRODUCTION: Nipple-areolar reconstruction (NAR) is the final phase of breast
      reconstruction and is associated with increased patient satisfaction. Nipple
      areolar reconstruction is typically performed in 2 separate stages, which include
      nipple reconstruction and tattooing of the nipple-areolar complex (NAC). Previous
      studies have demonstrated that increased duration of the reconstruction is
      associated with decreased patient satisfaction. Because a 2-stage reconstruction
      prolongs the reconstructive process, we introduce a simple and novel method of
      single-stage NAR (SS NAR), which combines the use of local flaps for nipple
      reconstruction and medical tattooing of the NAC in 1 session and delivers
      predictable outcomes with high patient satisfaction. METHODS: A retrospective
      chart review of patients who underwent SS NAR at our institution during the
      period from September 2010 to May 2012 was performed. Patient demographics,
      complications, outcomes, and overall patient satisfaction were assessed. A
      modified questionnaire (Likert scale) was used to assess patient satisfaction of
      nipple size, color, shape, and projection. RESULTS: Twenty-nine SS NARs were
      performed in 18 patients: 7 unilateral and 11 bilateral. Mean age was 45 years
      (range, 34-60 years). No major complications were identified. Mean length of
      follow-up was 10 months (range, 2-22 months). A 17% complication rate was
      observed: 14% (4/29) had irregular dye uptake of the areola, and 3% (1/29) had
      dehiscence from silicone guard pressure on the incision. Two patients underwent
      revisions: one patient underwent additional tattooing, and the other required
      flap readvancement and implant downsizing secondary to the wound dehiscence. We
      obtained a 70% survey response rate with 100% of responders who reported that
      they were "very satisfied" with NAC in each dimension. CONCLUSIONS: Our study
      demonstrates that SS NAR is a safe procedure with reproducible, excellent
      clinical results and very low complication rates or need for revisions. This
      method is cost-effective, convenient for the patient, and shortens patient
      recovery time with high patient satisfaction.

PMID- 24135689
TI  - Bilateral implant breast reconstruction: outcomes, predictors, and matched cohort
      analysis in 730 2-stage breast reconstructions over 10 years.
AB  - BACKGROUND: Rates of bilateral implant breast reconstruction (BI/BR) are rising
      despite the lack of precise information. Previous studies have examined
      unilateral reconstruction, making it difficult to counsel patients regarding the
      risk of BI/BR. The purpose of this study was to identify the incidence of
      complications and predictors of unfavorable aesthetic outcomes in the largest
      study to date of exclusive 2-stage BI/BR. Furthermore, a novel matched cohort
      analysis was conducted in patients who underwent contralateral prophylactic
      mastectomy and therapeutic mastectomy, whereby each patient acts as her own
      perfect internal control. METHODS: A retrospective chart review of consecutive
      patients who underwent BI/BR from 1997 to 2007 was performed to obtain patient
      demographics, treatment, and outcomes. Univariate and multivariate logistic
      regression analyses were performed to determine risk factors leading to the
      development of unfavorable aesthetic outcomes. chi test and Fisher exact analysis
      were used for matched-pairs analysis. RESULTS: Seven hundred thirty 2-stage
      BI/BRs were performed in 365 patients; perioperative complication rates were low
      at 9.3%. Long-term outcomes/unfavorable aesthetics were rippling (12.7%),
      capsular contracture (8.4%), and malposition (7.8%). After regression analysis,
      age [odds ratio (OR), 1.05], radiation (OR, 4.27), and length of follow-up (OR,
      1.48) were significantly associated with capsular contracture. Radiation (OR,
      0.26) and body mass index (OR, 0.95) were inversely associated with rippling. In
      the matched cohort, complication rates were similar between sides with
      malposition and rippling as significantly different aesthetic outcomes (P <
      0.05). Adjusted individual complication rates in the bilateral cohort of 18.4%
      were comparable with previous mixed and majority unilateral cohorts in the
      literature. CONCLUSIONS: Bilateral implant breast reconstruction has become
      increasingly prevalent for patients with breast cancer. Overall complications are
      low; BI/BR does not appear to incur additive risk. Matched cohort analysis
      confirmed low complication rates with only malposition and rippling as
      significant differences between sides.

PMID- 24135690
TI  - Please, be sensitive, specific, discriminative, and predictive ...

PMID- 24135691
TI  - Learning and memory: to sleep, perchance to forget.

PMID- 24135697
TI  - DSM-5 and RDoC: progress in psychiatry research?
AB  - Neuroscience studies into psychiatric disorders generally rely on disease
      definitions that are based on the influential Diagnostic and Statistical Manual
      of Mental Disorders (DSM), the fifth edition of which (DSM-5) was released
      earlier this year. Designed as a purely diagnostic tool, the DSM considers
      different disorders as distinct entities. However, boundaries between disorders
      are often not as strict as the DSM suggests. To provide an alternative framework
      for research into psychiatric disorders, the US National Institute of Mental
      Health (NIMH) has recently introduced its Research Domain Criteria (RDoC)
      project. In the RDoC, five 'domains' each reflect a brain system in which
      functioning is impaired, to different degrees, in different psychiatric
      conditions. Nature Reviews Neuroscience asked six leading investigators for their
      thoughts on how DSM-5 and the RDoC will influence neuroscience research into
      psychiatric disorders. 

PMID- 24135696
TI  - Modelling and analysis of local field potentials for studying the function of
      cortical circuits.
AB  - The past decade has witnessed a renewed interest in cortical local field
      potentials (LFPs)--that is, extracellularly recorded potentials with frequencies
      of up to ~500 Hz. This is due to both the advent of multielectrodes, which has
      enabled recording of LFPs at tens to hundreds of sites simultaneously, and the
      insight that LFPs offer a unique window into key integrative synaptic processes
      in cortical populations. However, owing to its numerous potential neural sources,
      the LFP is more difficult to interpret than are spikes. Careful mathematical
      modelling and analysis are needed to take full advantage of the opportunities
      that this signal offers in understanding signal processing in cortical circuits
      and, ultimately, the neural basis of perception and cognition.

PMID- 24135698
TI  - Bi-functional cross-linking reagents efficiently capture protein-DNA complexes in
      Drosophila embryos.
AB  - Chromatin immunoprecipitation (ChIP) is widely used for mapping DNA-protein
      interactions across eukaryotic genomes in cells, tissues or even whole organisms.
      Critical to this procedure is the efficient cross-linking of chromatin-associated
      proteins to DNA sequences that are in close proximity. Since the mid-nineties
      formaldehyde fixation has been the method of choice. However, some protein-DNA
      complexes cannot be successfully captured for ChIP using formaldehyde. One such
      formaldehyde refractory complex is the developmentally regulated insulator
      factor, Elba. Here we describe a new embryo fixation procedure using the bi
      functional cross-linking reagents DSG (disuccinimidyl glutarate) and DSP
      (dithiobis[succinimidyl propionate). We show that unlike standard formaldehyde
      fixation protocols, it is possible to capture Elba association with insulator
      elements in 2-5 h embryos using this new cross-linking procedure. We show that
      this new cross-linking procedure can also be applied to localize nuclear proteins
      that are amenable to ChIP using standard formaldehyde cross-linking protocols,
      and that in the cases tested the enrichment was generally superior to that
      achieved using formaldehyde cross-linking. 

PMID- 24135699
TI  - Isolation of community-acquired methicillin-resistant Staphylococcus aureus in
      healthy carriers in a Mexican community.
AB  - OBJECTIVES: Community-acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) clones are spreading rapidly among the population in many regions
      worldwide. Little information is available on CA-MRSA in Mexico. The aim of this
      study was to identify CA-MRSA strains in the nose and throat of healthy people in
      a Mexican community. METHODS: A total of 131 MRSA strains from the nose and
      throat obtained from healthy people in Mexico City were characterized. The genes
      mecA, lukS-PV/lukF-PV, and ACME-arcA were detected by PCR. Staphylococcal
      cassette chromosome mec (SCCmec), pulsed-field gel electrophoresis (PFGE), and
      spa typing were performed. RESULTS: Bacteria that had a Panton-Valentine
      leukocidin (PVL)-positive gene and SCCmec type IV or V were designated as CA-MRSA
      strains. We found that 21.4% of MRSA strains were CA-MRSA and that the percentage
      of CA-MRSA strains was similar in the nose and the throat. A great diversity of
      profiles was found in the strains identified by PFGE pattern and spa typing. Only
      one strain similar to the USA300 genotype was found; this strain carried the ACME
      arcA gene. CONCLUSIONS: CA-MRSA strains were detected in the nose and throat of
      healthy people. We identified a high level of genetic diversity among CA-MRSA
      strains in healthy people of Mexico City, which were different from the USA and
      pandemic clone profiles.

PMID- 24135700
TI  - Monte Carlo dosimetry of high dose rate gynecologic interstitial brachytherapy.
AB  - PURPOSE: To assess the dosimetric effects of the presence of the applicator, air
      pockets in clinical target volume (CTV) and OARs along with tissue
      heterogeneities using the Monte Carlo (MC) method in high dose rate (HDR)
      gynecologic interstitial brachytherapy with a Syed-Neblett template. METHODS AND
      MATERIALS: The CT based dosimetry has been achieved with the Geant4 MC toolkit
      version 9.2. DICOM-RT files of 38 patients were imported into our own platform
      for MC simulations. The dose distributions were then compared to those obtained
      with a conventional TG-43 calculation. RESULTS: Taking account of heterogeneities
      has effects of the order of 1% on the HDR gynecological dose distributions.
      However, the exclusion of air pockets and applicator from the DVH calculation can
      lower the CTV D90 and V100 by as much as 8.7% and 5.0% in comparison with TG-43.
      Rectum dosimetric indices can also be lowered by approximately 3% compared with
      TG-43 for most cases. Differences for urethra and bladder are for most cases
      below 1%. CONCLUSIONS: Exclusion of non-biological material such as air pockets
      and applicator volume from the CTV is important for both TG-43 and MC
      calculations. It could be easily implemented and automated in treatment planning
      systems without affecting computation times.

PMID- 24135701
TI  - Transcriptional stimulatory and repressive functions of histone H2B  ubiquitin
      ligase.

PMID- 24135702
TI  - DNA topoisomerases beyond the standard role.
AB  - Chromatin is dynamically changing its structure to accommodate and control DNA
      dependent processes inside of eukaryotic cells. These changes are necessarily
      linked to changes of DNA topology, which might itself serve as a regulatory
      signal to be detected by proteins. Thus, DNA Topoisomerases may contribute to the
      regulation of many events occurring during the transcription cycle. In this
      review we will focus on DNA Topoisomerase functions in transcription, with
      particular emphasis on the multiplicity of tasks beyond their widely appreciated
      role in solving topological problems associated with transcription elongation.

PMID- 24135703
TI  - Zinc'ing down RNA polymerase I.

PMID- 24135704
TI  - Regulation of context-specific gene expression by posttranscriptional  switches.

PMID- 24135705
TI  - Could ROS signals drive tissue-specific clocks?

PMID- 24135706
TI  - Transport and binding of tumor necrosis factor-alpha in articular cartilage
      depend on its quaternary structure.
AB  - The effect of tumor necrosis factor-alpha (TNFalpha) on cartilage matrix
      degradation is mediated by its transport and binding within the extracellular
      matrix (ECM) of the tissue, which mediates availability to cell receptors. Since
      the bioactive form of TNFalpha is a homotrimer of monomeric subunits, conversion
      between trimeric and monomeric forms during intratissue transport may affect
      binding to ECM and, thereby, bioactivity within cartilage. We studied the
      transport and binding of TNFalpha in cartilage, considering the quaternary
      structure of this cytokine. Competitive binding assays showed significant binding
      of TNFalpha in cartilage tissue, leading to an enhanced uptake. However, studies
      in which TNFalpha was cross-linked to remain in the trimeric form revealed that
      the binding of trimeric TNFalpha was negligible. Thus, binding of TNFalpha to ECM
      was associated with the monomeric form. Binding of TNFalpha was not disrupted by
      pre-treating cartilage tissue with trypsin, which removes proteoglycans and
      glycoproteins but leaves the collagen network intact. Therefore, proteoglycan
      loss during osteoarthritis should only alter the passive diffusion of TNFalpha
      but not its binding interaction with the remaining matrix. Our results suggest
      that matrix binding and trimer-monomer conversion of TNFalpha both play crucial
      roles in regulating the accessibility of bioactive TNFalpha within cartilage.

PMID- 24135707
TI  - Test-retest reliability of the infant car-seat challenge.
AB  - OBJECTIVE: To evaluate how a single infant car-seat challenge (ICSC) predicts
      subsequent respiratory physiology in premature infants. STUDY DESIGN: Prospective
      observational study of infants born at <37 weeks gestational age. Subjects
      underwent three ICSCs and we evaluated clinical characteristics, pass rate, and
      predictive value of a single ICSC pass. RESULT: Completed three ICSCs on 60
      subjects. Seven failed initial ICSC (11.7%). Those who failed had lower birth
      weights. Of the 53 that initially passed, 47 passed two subsequent tests (89%).
      Those who passed an initial test and failed a subsequent test had lower weights
      at each ICSC. CONCLUSION: Our results indicate that passing an ICSC is highly
      predictive of passing subsequent ICSCs. Lower weights at birth and at the time of
      ICSC were associated with increased risk of failure. We recommend including low
      birth weight as an inclusion criterion for ICSCs.

PMID- 24135708
TI  - Infants born at <29 weeks: pulmonary outcomes from a hybrid perinatal system.
AB  - OBJECTIVE: To assess pulmonary outcomes of infants <29 weeks gestational age
      (GA), delivered at level I, II and III facilities, to identify potentially
      modifiable factors affecting bronchopulmonary dysplasia (BPD) severity and to
      assess the external generalizability of the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development (NICHD) BPD Outcome Estimator.
      STUDY DESIGN: Outcomes for infants <29 weeks GA born during (2008-2010) and
      delivered either at an inborn level III center or in a level II or III
      metropolitan area hospital with transfer to a level IV center, or delivered in a
      distant level I or II center and then transported to a level IV center were
      assessed. BPD severity was compared with the NICHD Neonatal BPD Outcome
      Estimator. RESULT: Of 158 infants who comprised the cohort, 28 (17.8%) had no
      BPD, 39 (24.2%) had mild BPD, 45 (28.7%) had moderate BPD, 31 (19.7%) had severe
      BPD and 15 (9.6%) died at <=36 weeks post menstrual age. Site of birth did not
      predict severe BPD or death. Receiver operator characteristic curves showed fair
      predictability for none/mild and severe BPD. CONCLUSION: BPD severity was not
      dependent on site of birth. The NICHD BPD outcome estimator provides fair
      prediction for extreme outcomes.

PMID- 24135710
TI  - Two-year outcome after combination therapy for polypoidal choroidal vasculopathy:
      comparison with photodynamic monotherapy and anti-vascular endothelial growth
      factor monotherapy.
AB  - PURPOSE: To compare treatment outcomes of photodynamic therapy (PDT), anti
      vascular endothelial growth factor (VEGF) therapy and PDT combined with anti-VEGF
      therapy for polypoidal choroidal vasculopathy (PCV). PROCEDURES: A total of 62
      eyes of 62 patients who had completed at least 2 years of follow-up were
      retrospectively reviewed; 19 eyes received PDT only, 23 had anti-VEGF therapy
      only and 20 underwent combination therapy. Best-corrected visual acuity at
      baseline and each follow-up visit was investigated as a primary outcome measure.
      RESULTS: At year 2, the PDT and combination groups maintained significant visual
      improvement (p = 0.041 and p = 0.021), whereas the anti-VEGF group failed to do
      so (p = 0.673) when compared with the baseline. The combination group showed
      better visual outcome during follow-up, and significantly better visual outcome
      than the PDT group (p = 0.038) and the anti-VEGF group (p = 0.012) at year 2.
      CONCLUSIONS: Combination therapy leads to significantly better visual outcome
      than PDT and anti-VEGF monotherapy and is therefore a superior method for
      treating PCV, with a favorable visual outcome.

PMID- 24135711
TI  - Gene * environment interaction studies have not properly controlled for potential
      confounders: the problem and the (simple) solution.
AB  - Candidate gene * environment (G * E) interaction research tests the hypothesis
      that the effects of some environmental variable (e.g., childhood maltreatment) on
      some outcome measure (e.g., depression) depend on a particular genetic
      polymorphism. Because this research is inherently nonexperimental, investigators
      have been rightly concerned that detected interactions could be driven by
      confounders (e.g., ethnicity, gender, age, socioeconomic status) rather than by
      the specified genetic or environmental variables per se. In an attempt to
      eliminate such alternative explanations for detected G * E interactions,
      investigators routinely enter the potential confounders as covariates in general
      linear models. However, this practice does not control for the effects these
      variables might have on the G * E interaction. Rather, to properly control for
      confounders, researchers need to enter the covariate * environment and the
      covariate * gene interaction terms in the same model that tests the G * E term.
      In this manuscript, I demonstrate this point analytically and show that the
      practice of improperly controlling for covariates is the norm in the G * E
      interaction literature to date. Thus, many alternative explanations for G * E
      findings that investigators had thought were eliminated have not been. 

PMID- 24135713
TI  - Controlling nickel nanoparticle size in an organic/metal-organic matrix through
      the use of different solvents.
AB  - Nickel nanoparticles have been created in an organic-based matrix by the reaction
      of Ni(COD)2 (COD = 1,5-bis-cyclooctadiene) and 2,3,5,6-tetrafluoro-7,7,8,8
      tetracyanoquinodimethane (TCNQF4). The size of the nickel nanoparticles can be
      controlled by the use of different solvents and inclusion of tetrahydrofuran
      (THF) within the reaction to stabilise the Ni(0) atoms from the Ni(COD)2.
      Materials are characterised with a combination of X-ray diffraction, electron
      microscopy and magnetometry and it is found that samples made using a halocarbon
      solvent resulted in clustered bulk Ni particles (size <= 10 nm) with anomalously
      high superparamagnetic blocking temperatures. Using an isocyanide solvent
      produces smaller (size ~ 1 nm), well dispersed particles that show little
      evidence of superparamagnetic blocking in the range of temperatures investigated
      (>2 K). In all samples there is another component which dominates the magnetic
      response at low temperatures and shows an interesting temperature dependent
      scaling behaviour when plotted as M vs. B/T which we believe is related to the
      organo-metallic matrix that the particles are trapped within. We propose that the
      enhanced blocking temperature of particles synthesised using halocarbon solvents
      can be attributed to inter-particle dipolar interactions and nanoparticle-matrix
      exchange interactions. 

PMID- 24135712
TI  - Neuropsychiatric symptom profile differs based on pathology in patients with
      clinically diagnosed behavioral variant frontotemporal dementia.
AB  - BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is pathologically
      heterogeneous. With emerging therapeutics, determining underlying pathology
      during life is increasingly important. Neuropsychiatric symptoms are prevalent
      and diagnostic in bvFTD. METHODS: We assessed the neuropsychiatric profile of
      patients with clinically diagnosed bvFTD as a function of pathology at autopsy.
      Patients with a clinical diagnosis of bvFTD at the initial visit were selected
      from the National Alzheimer's Coordinating Center (NACC) database.
      Neuropsychiatric symptoms endorsed on the Neuropsychiatric Inventory
      Questionnaire (NPI-Q) were analyzed. RESULTS: Of 149 patients with clinically
      diagnosed bvFTD, pathology was primarily Alzheimer's disease (AD) in 20.5%. These
      patients differed from those with underlying frontotemporal lobar degeneration:
      patients with AD pathology (plaques and tangles) were more likely to have
      hallucinations, delusions, or agitation. Patients were further differentiated
      into tau-positive (30% of cases, including Pick's disease, FTD and parkinsonism
      with tau-positive or argyrophilic inclusions, and other tauopathies) or tau
      negative cases (70% of cases, including bvFTD tau-negative ubiquitin-positive
      inclusions). These patients also differed in some of the neuropsychiatric
      symptoms seen. Tau-negative cases were more likely to demonstrate depression,
      delusions, and changes in appetite and eating. CONCLUSIONS: These preliminary
      findings contribute to our increasing ability to predict, using simple clinical
      tools, the neuropathological underpinnings of bvFTD during life.

PMID- 24135714
TI  - Anisotropic dynamics of guest molecules in aerosol OT lamellar structures.
AB  - The present work is focused on developing a description of an anisotropic
      microheterogeneous medium, exploiting the dynamics of a guest molecule. The
      medium in question is the lamellar structures formed in the aqueous layer of
      ternary mixtures containing aerosol OT (AOT), water and n-heptane. The guest used
      in this study is the fluorescent probe, coumarin 153 (C153). The dynamics of this
      molecule, within the lamellar structure, have been studied using a combination of
      steady state and time resolved fluorescence, as well as fluorescence correlation
      spectroscopy (FCS). The fluorophore is strongly solvatochromatic and so, the
      wavelength of excitation can be tuned so as to selectively excite fluorescent
      molecules residing in different regions of the microheterogeneous media, even if
      the spatial separation between these regions is below the diffraction limit. The
      excitation wavelength in the present experiments is chosen so as to exclusively
      excite those C153 molecules that reside in the hydrophobic region of the lamellar
      structures. This triggers two different modes of diffusion, one along and the
      other perpendicular to the bilayers of the AOT. Thus, the dynamics of the
      fluorescent probe provide an elegant manifestation of the anisotropy of the host
      medium. 

PMID- 24135709
TI  - Neurodevelopmental outcomes of extremely low birth weight infants with
      spontaneous intestinal perforation or surgical necrotizing enterocolitis.
AB  - OBJECTIVE: To determine if extremely low birth weight infants with surgical
      necrotizing enterocolitis have a higher risk of death or neurodevelopmental
      impairment and neurodevelopmental impairment among survivors (secondary outcome)
      at 18-22 months corrected age compared with infants with spontaneous intestinal
      perforation and infants without necrotizing enterocolitis or spontaneous
      intestinal perforation. STUDY DESIGN: Retrospective analysis of the Neonatal
      Research Network very low birth weight registry, evaluating extremely low birth
      weight infants born between 2000 and 2005. The study infants were designated into
      three groups: (1) spontaneous intestinal perforation without necrotizing
      enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3)
      neither spontaneous intestinal perforation nor necrotizing enterocolitis.
      Multivariate logistic regression analysis was performed to evaluate the
      association between the clinical group and death or neurodevelopmental
      impairment, controlling for multiple confounding factors including center.
      RESULT: Infants with surgical necrotizing enterocolitis had the highest rate of
      death before hospital discharge (53.5%) and death or neurodevelopmental
      impairment (82.3%) compared with infants in the spontaneous intestinal
      perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no
      spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar
      results were observed for neurodevelopmental impairment among survivors. On
      logistic regression analysis, both spontaneous intestinal perforation and
      surgical necrotizing enterocolitis were associated with increased risk of death
      or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence
      interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and
      neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2
      and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively). CONCLUSION: Spontaneous
      intestinal perforation and surgical necrotizing enterocolitis are associated with
      a similar increase in the risk of death or neurodevelopmental impairment and
      neurodevelopmental impairment among extremely low birth weight survivors at 18-22
      months corrected age.

PMID- 24135715
TI  - A novel acoustic emission beamforming method with two uniform linear arrays on
      plate-like structures.
AB  - A novel acoustic emission (AE) source localization approach based on beamforming
      with two uniform linear arrays is proposed, which can localize acoustic sources
      without accurate velocity, and is particularly suited for plate-like structures.
      Two uniform line arrays are distributed in the x-axis direction and y-axis
      direction. The accurate x and y coordinates of AE source are determined by the
      two arrays respectively. To verify the location accuracy and effectiveness of the
      proposed approach, the simulation of AE wave propagation in a steel plate based
      on the finite element method and the pencil-lead-broken experiment are conducted,
      and the AE signals obtained from the simulations and experiments are analyzed
      using the proposed method. Moreover, to study the ability of the proposed method
      more comprehensive, a plate of carbon fiber reinforced plastics is taken for the
      pencil-lead-broken test, and the AE source localization is also realized. The
      results indicate that the two uniform linear arrays can localize different
      sources accurately in two directions even though the localizing velocity is
      deviated from the real velocity, which demonstrates the effectiveness of the
      proposed method in AE source localization for plate-like structures. 

PMID- 24135716
TI  - Transcriptional establishment of cell-type identity: dynamics and causal
      mechanisms of T-cell lineage commitment.
AB  - Precursor cell entry into the T-cell developmental pathway can be divided into
      two phases by the closure of T-lineage commitment. As cells decide against the
      last alternative options to the T-cell fate, they turn on the transcription
      factor Bcl11b and silence expression of a group of multipotent progenitor
      regulatory factors that include hematopoietic transcription factor PU.1.
      Functional perturbation tests show that Bcl11b is needed for commitment while
      PU.1 actively participates in keeping open access to alternative fates, until it
      is silenced; however, PU.1 and Bcl11b both contribute positively to T-cell
      development. Our recent work reviewed here sheds light on the transcriptional
      regulatory network that determines the timing and irreversibility of Bcl11b
      activation, the ways that Notch signaling from the thymic microenvironment
      restricts the action of PU.1 to prevent it from diverting cells to non-T fates,
      and the target genes that PU.1 still regulates under the influence of Notch
      signaling to contribute to T-cell generation. We argue that T-cell development
      depends on the sequential operation of two interlaced, but mutually antagonistic,
      gene regulatory networks, one initially supporting expansion before commitment
      and the other imposing a "terminal" differentiation process on committed cells. 

PMID- 24135717
TI  - Immune surveillance of unhealthy cells by natural killer cells.
AB  - Pathogenic and oncogenic insults result in the induction of intrinsic defense
      mechanisms such as cell-death pathways and senescence, and extrinsic pathways
      that mobilize immune responses to destroy unhealthy cells. Both protective
      mechanisms presumably evolved to limit the damage these insults could inflict on
      the host. After viral infection or malignant transformation, unhealthy cells can
      be directly sensed by natural killer (NK) and some T cells via the activating
      receptor NKG2D. All NK cells and subsets of T cells express NKG2D. The
      NKG2D/ligand system represents a major recognition mechanism for detection and
      elimination of unhealthy cells. Here we discuss different pathways, including
      stress pathways, that are responsible for cell-surface display of ligands for
      NKG2D, which are self-proteins that are minimally expressed by normal cells. We
      also discuss new results indicating that efficient elimination of tumor cells
      that display NKG2D ligands depends on the recruitment of NK cells and other
      immune cells to the tumor, which can be regulated by distinct mechanisms,
      including the p53-dependent production of chemokines by senescent tumors. The
      cooperative effect of pathways that induce the display of NKG2D ligands and
      distinct pathways that mobilize immune cells provides a higher degree of
      specificity to the NK cell response. 

PMID- 24135718
TI  - Extensive diversification of MHC in Chinese giant salamanders Andrias davidianus
      (Anda-MHC) reveals novel splice variants.
AB  - A series of MHC alleles (including 26 class IA, 27 class IIA, and 17 class IIB)
      were identified from Chinese giant salamander Andrias davidianus (Anda-MHC).
      These genes are similar to classical MHC molecules in terms of characteristic
      domains, functional residues, deduced tertiary structures and genetic diversity.
      The majority of variation between alleles is found in the putative peptide
      binding region (PBR), which is driven by positive Darwinian selection. The
      coexistence of two isoforms in MHC IA, IIA, and IIB alleles are shown: one full
      length transcript and one novel splice variant. Despite lake of the external
      domains, these variants exhibit similar subcellular localization with the full
      length transcripts. Moreover, the expression of MHC isoforms are up-regulated
      upon in vivo and in vitro stimulation with Andrias davidianus ranavirus (ADRV),
      suggesting their potential roles in the immune response. The results provide
      insights into understanding MHC variation and function in this ancient and
      endangered urodele amphibian.

PMID- 24135720
TI  - Preserving cognition, quality of life, physical health and functional ability in
      Alzheimer's disease: the effect of physical exercise (ADEX trial): rationale and
      design.
AB  - BACKGROUND: Exercise is hypothesized to improve cognition, physical performance,
      functional ability and quality of life, but evidence is scarce. Previous studies
      were of short duration, often underpowered and involving home-based light
      exercise programs in patients with undefined dementia. The aim of the ADEX
      ('Preserving Cognition, Quality of Life, Physical Health and Functional Ability
      in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish
      whether aerobic exercise is effective in improving cognition as well as in
      reducing the prevalence of psychiatric symptoms among patients with Alzheimer's
      disease (AD). METHODS: The ADEX study is a multicenter, single-blind, randomized
      trial with two arms: an intervention group attending 16 weeks of continuously
      supervised moderate-to-high intensity aerobic exercise and a control group
      receiving usual care. We plan to recruit 192 patients with mild AD. The primary
      outcome measure is change from baseline in cognitive performance at 16 weeks (as
      measured by the Symbol Digit Modalities test). CONCLUSIONS: To our knowledge this
      is the first large-scale controlled study to investigate the effects of
      supervised moderate aerobic exercise on cognition in patients with AD.
      Recruitment began in January 2012 and results are expected to be available in
      2014. We summarize the methodological challenges we and other studies have faced
      in this type of complex multicenter intervention with unique challenges to study
      design.

PMID- 24135719
TI  - Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue
      virus infection.
AB  - Upon exposure to dengue virus, the Aedes aegypti mosquito vector mounts an anti
      viral immune defense by activating the Toll, JAK/STAT, and RNAi pathways, thereby
      limiting infection. While these pathways and several other factors have been
      identified as dengue virus antagonists, our knowledge of factors that facilitate
      dengue virus infection is limited. Previous dengue virus infection-responsive
      transcriptome analyses have revealed an increased mRNA abundance of members of
      the myeloid differentiation 2-related lipid recognition protein (ML) and the
      Niemann Pick-type C1 (NPC1) families upon dengue virus infection. These genes
      encode lipid-binding proteins that have been shown to play a role in host
      pathogen interactions in other organisms. RNAi-mediated gene silencing of a ML
      and a NPC1 gene family member in both laboratory strain and field-derived Ae.
      aegypti mosquitoes resulted in significantly elevated resistance to dengue virus
      in mosquito midguts, suggesting that these genes play roles as dengue virus
      agonists. In addition to their possible roles in virus cell entry and
      replication, gene expression analyses suggested that ML and NPC1 family members
      also facilitate viral infection by modulating the mosquito's immune competence.
      Our study suggests that the dengue virus influences the expression of these genes
      to facilitate its infection of the mosquito host. 

PMID- 24135721
TI  - Methotrexate-associated lymphoproliferative disorder diagnosed by skin biopsy in
      a patient with multiple systemic nodules.

PMID- 24135722
TI  - Expression profile of microRNA-200 family in hepatocellular carcinoma with bile
      duct tumor thrombus.
AB  - OBJECTIVE: The aim of this study was to assess the role of the miR-200 family in
      the pathogenesis of hepatocellular carcinoma with bile duct tumor thrombus (HCC
      BDTT). BACKGROUND: Hepatocellular carcinoma with bile duct tumor thrombus is a
      challenging condition because of its rarity and dismal prognosis. Epithelial-to
      mesenchymal transition (EMT) is considered a critical step in the progression and
      metastasis of HCC and is regulated by the microRNA-200 (miR-200) family. METHODS:
      Thirty patients with HCC-BDTT were enrolled and 1240 patients with conventional
      HCC (cHCC) served as clinicopathologic controls. Sixty age- and sex-matched cHCC
      patients were selected to compare the miR-200 family expression profile and
      immunohistochemical characteristics. Gain- and loss-of-function studies of the
      miR-200 family were conducted using the hepatoma cell lines. RESULTS: Although
      the mean size of HCC-BDTT was smaller than that of cHCC, the former had a higher
      incidence of vascular invasion and a poorer long-term survival. The expressions
      of miR-200c and miR-141 were downregulated in HCC-BDTT (4.5- and 4.8-fold
      decrease, respectively). Downregulation of both miR-200c and miR-141
      independently predicted disease-free survival. The HCC-BDTT, but not cHCC,
      exhibited overexpression of ZEB1, Twist, transforming growth factor-beta receptor
      type II, and vimentin, and aberrant E-cadherin expression, indicating EMT. The
      HCC-BDTT demonstrated increased expression in IL-6 and stemness factor Bmi1, but
      reduced level of metastasis-suppressive protein, insulin-like growth factor
      binding protein 4. The invasive ability of the highly aggressive Mahlavu cell was
      attenuated by pre-miR-200c+141, whereas the invasive ability of the less
      aggressive Huh7 cell was enhanced by anti-miR-200c+141. CONCLUSIONS: Simultaneous
      silencing of miR-200c and miR-141 was likely to be responsible for the
      development of HCC-BDTT via ZEB1-directed EMT activation and Sec23a-mediated
      secretome.

PMID- 24135723
TI  - DNA methylation pattern of CALCA in preterm neonates with bacterial sepsis as a
      putative epigenetic biomarker.
AB  - Diagnosis of bacterial sepsis in preterm neonates can be difficult when using
      serum markers that rely on physiological changes because these changes may not
      necessarily be the result of bacterial infections alone. This retrospective
      investigation explores the potential use of the DNA methylation pattern of CpG
      sites in the promoter region of the calcitonin-related polypeptide alpha (CALCA)
      gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four
      novel changes in the DNA methylation of eight CpG sites were detected in this
      gene and are present only in neonates with bacterial sepsis: (1) partial
      methylation at -769 CpG in gram-negative or gram-positive early onset sepsis
      (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram
      negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of
      7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G>T:A; 5' de novo 
      778 CpG mutation on both alleles in EOS. These changes were not detected in birth
      weight and gestational age matched controls or in newborns with isolated
      infections. Our results indicate that the DNA methylation pattern of the promoter
      region of the CALCA gene varies in different types of bacterial preterm sepsis,
      thus suggesting a potential use as an epigenetic biomarker. A prospective
      confirmation of these results is essential. 

PMID- 24135725
TI  - Terminal dual-labeling of a transcribed RNA.
AB  - We report here a site-specific terminal dual-labeling strategy for a transcribed
      RNA. The combination of 5'-thiophosphoryl and 3'-amino functionalities enables
      efficient RNA dual labeling with different fluorophores at both 5'- and 3'
      terminal positions specifically. This dual-labeling strategy is applied to pre
      miRNA for construction of molecular beacons. The RNA beacons in their native
      hairpin formation bring the fluorophore and quencher groups into close proximity,
      leading to fluorescence quenching by FRET effect. Ribonuclease (dicer enzyme or
      micrococcal nuclease) can efficiently cleave RNA beacons leading to concentration
      and time-dependent fluorescence increase. The dual-labeling strategy for
      transcribed RNAs involves only commercially available reagents, enzymes and
      native RNA, making it more accessible for general applications. 

PMID- 24135724
TI  - Discovery, design and synthesis of a selective S1P(3) receptor allosteric
      agonist.
AB  - Potent and selective S1P3 receptor (S1P3-R) agonists may represent important
      proof-of-principle tools used to clarify the receptor biological function and
      assess the therapeutic potential of the S1P3-R in cardiovascular, inflammatory
      and pulmonary diseases. N,N-Dicyclohexyl-5-propylisoxazole-3-carboxamide was
      identified by a high-throughput screening of MLSMR library as a promising S1P3-R
      agonist. Rational chemical modifications of the hit allowed the identification of
      N,N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide, a S1P3-R agonist endowed
      with submicromolar activity and exquisite selectivity over the remaining
      S1P1,2,4,5-R family members. A combination of ligand competition, site-directed
      mutagenesis and molecular modeling studies showed that the N,N-dicyclohexyl-5
      cyclopropylisoxazole-3-carboxamide is an allosteric agonist and binds to the S1P3
      R in a manner that does not disrupt the S1P3-R-S1P binding. The lead molecule
      herein disclosed constitutes a valuable pharmacological tool to explore the
      molecular basis of the receptor function, and provides the bases for further
      rational design of more potent and drug-like S1P3-R allosteric agonists. 

PMID- 24135726
TI  - The functional group on (E)-4,4'-disubstituted stilbenes influences toxicity and
      antioxidative activity in differentiated PC-12 cells.
AB  - This work probes the relationship between stilbene functional group and
      biological activity. The biological activity of synthesized stilbenes (E)-4,4'
      dicyanostilbene, (E)-4,4'-diacetylstilbene, (E)-4,4'-diaminostilbene, a novel
      stilbene, 1,1'-(vinylenedi-p-phenylene)diethanol, and (E)-stilbene was assessed
      at biologically relevant nanomolar concentrations using the MTS cell viability
      assay in differentiated PC-12 cells under optimal culture conditions and
      conditions of oxidative stress. Under optimal culture conditions the synthesized
      stilbene derivatives were found to be non-toxic to cells at concentrations up to
      10 MUg/ml. To mimic oxidative stress, the activity of these stilbene derivatives
      in the presence of 0.03% H2O2 was investigated. Stilbene derivatives with
      electron-withdrawing functional groups were 2-3 times more toxic than the H2O2
      control, indicating that they may form toxic metabolites in the presence of H2O2.
      Fluorescence data supported that stilbene derivatives with electron-withdrawing
      functional groups, (E)-4,4'-dicyanostilbene and (E)-4,4'-diacetylstilbene, may
      react with H2O2. In contrast, the stilbene derivative with a strong electron
      donating functional group, (E)-4,4'-diaminostilbene, rescued neurons from H2O2
      induced toxicity. The DPPH assay confirmed that (E)-4,4'-diaminostilbene is able
      to scavenge free radicals. These data indicate that the Hammett value of the
      functional group correlates with the biological activity of (E)-4,4'
      disubstituted stilbenes in differentiated PC-12 cells.

PMID- 24135728
TI  - Discovery of cyantraniliprole, a potent and selective anthranilic diamide
      ryanodine receptor activator with cross-spectrum insecticidal activity.
AB  - Anthranilic diamides are an exceptionally active class of insect control
      chemistry that selectively activates insect ryanodine receptors causing mortality
      from uncontrolled release of calcium ion stores in muscle cells. Work in this
      area led to the successful commercialization of chlorantraniliprole for control
      of Lepidoptera and other insect pests at very low application rates. In search of
      lower logP analogs with improved plant systemic properties, exploration of cyano
      substituted anthranilic diamides culminated in the discovery of a second product
      candidate, cyantraniliprole, having excellent activity against a wide range of
      pests from multiple insect orders. Here we report on the chemistry, biology and
      structure-activity trends for a series of cyanoanthranilic diamides from which
      cyantraniliprole was selected for commercial development. 

PMID- 24135727
TI  - Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3
      protease inhibitors.
AB  - Herein, we report the synthesis and structure-activity relationship studies of
      new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and
      spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and
      2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC50=0.8
      MUM).

PMID- 24135729
TI  - [Malignant hyperthermia: multifactorial events leading to a crisis].
AB  - This case-report focused on the occurrence of a crisis of malignant hyperthermia
      on a young biker (21 y.o.) victim of a severe traffic accident. This observation
      gives some key points: the delayed occurrence of the crisis after 4 hours of
      surgery, the multi-factorial events that triggered the crisis; the choice to
      perform a quick diagnosis through gene analysis in comparison to the standard
      tests of caffeine on a muscular biopsy. These different points are discussed with
      a proposal of algorithm in the situation.

PMID- 24135730
TI  - [Economic impact of strategies using ephedrine prefilled syringes].
AB  - OBJECTIVES: Ephedrine is an emergency drug available in ampules and syringes need
      to be prepared in advance according to one of two strategies in our
      establishment: strategy 1 (S1: 1 ampule per patient) and strategy 2 (S2: 1 ampule
      per operating room). There are also prefilled syringes. Because of their high
      cost and conflicting results in the literature, we assessed the economic interest
      of using prefilled syringes compared with strategies S1 and S2. TYPE OF STUDY:
      This was a prospective observational study. PATIENTS AND METHODS: The consumption
      of ephedrine was recorded over two periods of 14 days: P1 with syringes prepared
      in advance according to S1 or S2 and P2 with the on-demand use of prefilled
      syringes. RESULTS: The cost of a syringe of ephedrine prepared in advance (nurse
      time preparation included) was evaluated at ?1.65 vs. ?3.57 for a prefilled
      syringe. In operating rooms using S1, the use of prefilled syringes reduced
      overall the cost per patient about ?1.22 and global annual costs by 72% (?2830),
      while the decrease was about ?0.32 for the cost per patient and about 47% (?2760)
      for global annual costs for operating rooms using S2. CONCLUSION: The interest of
      our study is that we investigated different supply strategies for ephedrine
      within a large number of operating rooms. In our establishment, it was decided to
      use prefilled syringes in operating rooms that used S1. As well as the economic
      interest, prefilled syringes contributed to improved safety and saved nursing
      time.

PMID- 24135731
TI  - [ICU patients and days of intensive care: A mathematical model optimizing the
      consequences of ICU unit function, intensive care and continual monitoring on
      incurred supplementary costs].
AB  - INTRODUCTION: "Critical Care Units" are intended to admit patients with multiple
      organ failure. The severity of patients admitted is variable. The aim of the
      study was to estimate the number of days that an optimum care organization could
      release, and therefore the additional admissions that would have been allowed.
      Estimates of earnings related to the various supplements were carried out
      jointly. METHODS: Reporting days associated or not with a resuscitation care
      during the year 2011 in an ICU of a university hospital (16 beds), optimized
      patient flow simulation, and computation of medical act inducing financial
      supplements. RESULTS: Six hundred and fifty-seven patients (SAPS II from 0 to
      110, 41% ventilated more than 48hours, mortality=26%) were admitted representing
      5095days (occupancy rate=87%). Two hundred and twenty-two patients (34%) did not
      trigger supplement for resuscitation care for 415days in the unit. Four hundred
      and thirty-five patients have triggered this supplement representing 4680days,
      including 3035days with resuscitation care and 1645 (35% of days valued
      resuscitation, 32% of total days) without any. The entire year 2011 has generated
      earnings of 3,980,192?. Optimization of management would have allowed the
      admission of additional 235 to 295 patients and potential additional earnings
      from 524,735? to 1,063,804?, depending on the occupancy rate chosen (80% or real
      2011s) and the severity of discharged patients. CONCLUSION: Optimization of the
      patients flow between "Critical Care", Intensive Care and Continuous Monitoring
      Units would increase the number of patients admitted in "Critical Care" Units
      without any financial loss related to supplements.

PMID- 24135732
TI  - An AC electrokinetic impedance immunosensor for rapid detection of tuberculosis.
AB  - This work presents an AC electrokinetic impedance sensing method that is capable
      of detecting specific interactions between macromolecules such as antigen
      antibody binding. Serum samples were added to the surface of interdigitated
      electrodes that had been coated with bacterial antigens. After applying an AC
      signal of 100 mV at a specific frequency continuously, the electrodes' impedance
      change was recorded and used to determine the occurrence and level of antibody
      binding to the antigen. Our theoretical analysis indicated that with this AC
      signal, the target macromolecules will experience a sufficiently strong
      attraction force towards the electrode surface for acceleration of the binding
      process. Using this method, 11 human tuberculosis and 10 bovine tuberculosis
      serum samples were tested. The results were consistent with those obtained by a
      conventional ELISA method. The limit of detection of the impedance sensing method
      was estimated to be better than 10 ng mL(-1). In summary, we demonstrate that AC
      electrokinetic impedance sensing can be used for rapid and sensitive detection of
      specific antibodies in serum samples. This method may form a basis for
      development of a point of care diagnostic device for human and bovine
      tuberculosis. 

PMID- 24135733
TI  - Diagnostic accuracy measures.
AB  - BACKGROUND: An increasing number of diagnostic tests and biomarkers have been
      validated during the last decades, and this will still be a prominent field of
      research in the future because of the need for personalized medicine. Strict
      evaluation is needed whenever we aim at validating any potential diagnostic tool,
      and the first requirement a new testing procedure must fulfill is diagnostic
      accuracy. SUMMARY: Diagnostic accuracy measures tell us about the ability of a
      test to discriminate between and/or predict disease and health. This
      discriminative and predictive potential can be quantified by measures of
      diagnostic accuracy such as sensitivity and specificity, predictive values,
      likelihood ratios, area under the receiver operating characteristic curve,
      overall accuracy and diagnostic odds ratio. Some measures are useful for
      discriminative purposes, while others serve as a predictive tool. Measures of
      diagnostic accuracy vary in the way they depend on the prevalence, spectrum and
      definition of the disease. In general, measures of diagnostic accuracy are
      extremely sensitive to the design of the study. Studies not meeting strict
      methodological standards usually over- or underestimate the indicators of test
      performance and limit the applicability of the results of the study. KEY
      MESSAGES: The testing procedure should be verified on a reasonable population,
      including people with mild and severe disease, thus providing a comparable
      spectrum. Sensitivities and specificities are not predictive measures. Predictive
      values depend on disease prevalence, and their conclusions can be transposed to
      other settings only for studies which are based on a suitable population (e.g.
      screening studies). Likelihood ratios should be an optimal choice for reporting
      diagnostic accuracy. Diagnostic accuracy measures must be reported with their
      confidence intervals. We always have to report paired measures (sensitivity and
      specificity, predictive values or likelihood ratios) for clinically meaningful
      thresholds. How much discriminative or predictive power we need depends on the
      clinical diagnostic pathway and on misclassification (false positives/negatives)
      costs.

PMID- 24135734
TI  - The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial
      with young men who have sex with men.
AB  - BACKGROUND: This study examined the feasibility of a combination prevention
      intervention for young men who have sex with men (YMSM), an anticipated target
      population for HIV preexposure prophylaxis (PrEP). METHODS: Project PrEPare, a
      pilot study using a randomized 3-arm design, compared an efficacious behavioral
      HIV prevention intervention (Many Men, Many Voices-3 MV) alone, 3 MV combined
      with PrEP (tenofovir/emtricitabine), and 3 MV combined with placebo. Eligible
      participants were 18- to 22-year-old HIV-uninfected men who reported unprotected
      anal intercourse in the past year. Participants were screened for preliminary
      eligibility at youth venues and community organizations and were also referred
      through social networks. Laboratory screening determined final eligibility.
      Behavioral and biomedical data were collected at baseline and every 4 weeks
      thereafter for 24 weeks. RESULTS: Sixty-eight youth (mean age = 19.97 years; 53%
      African American, 40% Latino) were enrolled; 58 were randomized. Self-reported
      medication adherence averaged 62% (range, 43%-83%), whereas rates of detectable
      tenofovir in plasma of participants in the emtricitabine/tenofovir disoproxil
      fumarate arm ranged from 63.2% (week 4) to 20% (week 24). There were 5 >= grade 2
      adverse events possibly/probably related to the study medication. Sexual risk
      behavior declined from baseline to week 24 in all study arms. CONCLUSIONS: The
      feasibility of enrolling at-risk youth, particularly young men who have sex with
      men of color, into Project PrEPare has been demonstrated. The acceptability of
      the group intervention along with counseling and testing was high. Self-reported
      medication adherence and corresponding plasma drug concentrations were low
      indicating the need for enhanced adherence counseling. Exploration of PrEP use
      among youth in nonrandomized open label trials is warranted.

PMID- 24135735
TI  - Controlling healthcare-associated infections in the international research
      setting.

PMID- 24135736
TI  - Comment on "Higher CNS penetration-effectiveness of long-term combination
      antiretroviral therapy is associated with better HIV-1 viral suppression in
      cerebrospinal fluid".

PMID- 24135737
TI  - Incorrect beliefs about male circumcision and male-to-female HIV transmission
      risk in South Africa: implications for prevention.

PMID- 24135738
TI  - The utility of the elbow sign in the diagnosis of OSA.
AB  - BACKGROUND: Multiple questionnaires have been used to predict the diagnosis of
      OSA. Such models typically have multiple questions requiring cumulative scoring
      for interpretation. We wanted to determine whether a simple two-part
      questionnaire has predictive value in the pretest clinical evaluation for OSA.
      METHODS: A questionnaire consisting of two questions--(1) Does your bed partner
      ever poke or elbow you because you are snoring? and (2) Does your bed partner
      ever poke or elbow you because you have stopped breathing?--was prospectively
      administered to patients evaluated in a sleep disorders clinic prior to
      undergoing polysomnography. Age, sex, BMI, and Epworth Sleepiness Scale data were
      collected. RESULTS: Among the 128 patients who had a polysomnogram, answering
      "yes" to being awakened for snoring increased the OR of an apnea-hypopnea
      index>=5/h 3.9 times compared with "no." Answering "yes" to being awakened for
      apneic spells was associated with an OR of 5.8 for an apnea-hypopnea index>=5/h
      compared with "no." These associations did not differ by sex, BMI, Epworth
      Sleepiness Scale or answering "yes" to the other question. Subjects>50 years old
      with OSA were less likely to report a positive elbow sign and had a significantly
      lower OR for being awakened for apneic spells than those<50 years old. The
      sensitivity and specificity of being awakened for apneic spells was 65% and 76%,
      respectively, with a positive predictive value of 90%. Subgroup analysis revealed
      that in men with a BMI>31 a positive elbow sign had a specificity of 96.6% for a
      diagnosis of OSA. CONCLUSIONS: Among patients referred to a sleep disorders
      clinic, a positive response to being elbowed/poked for apneic spells
      significantly improves the pretest prediction of OSA.

PMID- 24135741
TI  - Maintaining professionalism as a physician is not a small task.

PMID- 24135742
TI  - Middle ear reconstruction using the titanium Kurz Variac partial ossicular
      replacement prosthesis: functional results.
AB  - IMPORTANCE: Satisfactory functional results following ossicular chain
      reconstruction mainly depend on a stable connection between the tympanic membrane
      and the stapes, which is in turn dependent on the type of prosthesis used.
      Knowledge about the safety and functional outcome of the commercially available
      middle ear prostheses is therefore of great importance. OBJECTIVE: To evaluate
      the efficacy and safety of the Kurz TTP-Variac System partial ossicular
      replacement prosthesis (PORP) in ossiculoplasty. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective review of all ossiculoplasties performed by 1 surgeon
      at a secondary referral center from August 2006 through July 2012. Participants
      were patients with cholesteatoma, chronic otitis media, or ossicular chain
      disruption in the absence of inflammatory disease who underwent ossicular
      reconstruction. EXPOSURE Ossiculoplasty using a Kurz TTP-Variac System PORP. MAIN
      OUTCOMES AND MEASURES: Mean preoperative and postoperative air-bone gaps (ABGs)
      and improvements in ABG were analyzed for each frequency by means of a 4
      frequency pure-tone average. Successful postoperative hearing was defined as
      postoperative ABG smaller than 20 dB. RESULTS: Eighty-nine ears in 83 patients
      aged 7 to 85 years were included. Transmeatal tympanoplasty was performed in 17
      ears (19%). Seven ears (8%) underwent tympanoplasty with canal wall-down
      mastoidectomy, and 65 ears (73%) underwent canal wall-up (combined approach)
      tympanoplasty with mastoidectomy. The study population comprised 61 primary
      tympanoplasties (69%) and 28 revision cases (31%). Mean follow-up was 13 months.
      Overall, the ABG significantly improved from a mean (SD; range) of 26.19 (11.53;
      3.75-51.25) dB to 15.58 (9.80; 0-48.75) dB (P < .01 for all frequencies). Mean
      ABG improvement was 10.62 dB. Successful postoperative hearing was obtained in 65
      ears (73%). Revision surgery, especially in ears with ossicular chain disruption
      without inflammatory disease, was associated with poorer functional outcome,
      whereas preservation of the malleus was associated with a better functional
      outcome (P < .05). There were few complications (1 prosthesis extrusion, 2
      prosthesis dislocations, 2 reperforations, 3 cases of residual cholesteatoma, and
      3 of light sensorineural hearing loss). CONCLUSIONS AND RELEVANCE: The titanium
      Kurz TTP-Variac System PORP is an effective prosthesis to reconstruct the
      ossicular chain. Complications are rare, illustrating the safety of the
      prosthesis.

PMID- 24135743
TI  - Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas.
AB  - IMPORTANCE: Infantile hemangiomas (IHs) vary substantially in localization and
      extent of tissue involvement, but IH biological progression is remarkably unique
      and predictable. Propranolol is an effective treatment for symptomatic IH, but
      its mechanism of action remains unknown and understudied. OBJECTIVE: To compare
      excreted proteins in infants with IH being treated with propranolol vs
      prednisolone. DESIGN, SETTING, AND PARTICIPANTS: Exploratory urine proteomics
      profiling of patients with IH from July 2010 to September 2012 at a tertiary
      pediatric hospital. Participants were infants with IH treated at our institution
      who were participating in a blinded, randomized trial comparing prednisolone vs
      propranolol. They ranged in age from 14 days to 15 months at enrollment.
      Exclusion criteria included a history of diabetes mellitus, asthma, and/or
      cardiovascular disease including hypertension or hypotension. Urine samples were
      longitudinally collected from all participants. Specimens were desalted,
      concentrated, and gel fractionated, and the protein content was identified using
      liquid chromatography tandem mass spectrometry. Western blot analyses and enzyme
      linked immunosorbent assays (ELISAs) were performed to validate mass spectrometry
      findings. INTERVENTION: Treatment with propranolol or prednisolone administered
      starting before the age of 6 months. MAIN OUTCOMES AND MEASURES: Proteins present
      in urine samples and change in urinary levels of proteins over time. RESULTS:
      Samples were obtained from 3 patients treated with prednisolone, 3 patients
      treated with propranolol, and 5 untreated controls with IH. More than 1000
      urinary proteins were identified by proteomics. Patients treated with propranolol
      demonstrated attenuation of excreted matrix metalloproteinase 9 (MMP-9) in urine
      over the proliferative phase of the condition compared with prednisolone-treated
      patients. These findings were validated with Western blot analysis and quantified
      with ELISA, which confirmed mean urinary MMP-9 levels in the first year of life
      to be significantly lower in propranolol-treated patients with IH compared with
      prednisolone-treated patients with IH (0.118 vs 0.501 ng/mL; P = .03) or with
      nontreated patients with IH (0.118 vs 3.69 ng/mL; P = .02). CONCLUSIONS AND
      RELEVANCE: Propranolol treatment decreases urinary excretion of MMP-9 in patients
      with IH. Matrix metalloproteinase 9 may be a biomarker for IH propranolol
      responsiveness, and its signaling pathways may represent the molecular target of
      this drug.

PMID- 24135744
TI  - Transoral robotic-assisted lingual tonsillectomy in the pediatric population.
AB  - IMPORTANCE: Since technologic advances allow the use of robotic assistance in
      various surgical interventions performed to treat pediatric otolaryngology
      patients, the feasibility and outcomes of potential procedures must be assessed.
      OBJECTIVE: To assess the feasibility and outcomes of robotic-assisted lingual
      tonsillectomy in the pediatric population. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective medical record review in a tertiary care children's hospital of 16
      pediatric patients who underwent robotic-assisted lingual tonsillectomy from
      March 1, 2011, through December 31, 2012. INTERVENTION: All patients underwent
      robotic-assisted lingual tonsillectomy using the da Vinci Surgical System
      (Intuitive Surgical, Inc) at the Children's Hospital of Pittsburgh of the
      University of Pittsburgh Medical Center. MAIN OUTCOMES AND MEASURES: Demographic
      data, comorbidities, robot docking time, operative time, estimated blood loss,
      and postoperative course, including complications in the immediate and longer
      term postoperative period, were collected and analyzed. RESULTS: All patients
      successfully underwent lingual tonsillectomy using the da Vinci Surgical System.
      Endotracheal intubation was performed in all patients and did not interfere with
      visualization of the oropharynx. Optimal retraction allowed visualization of
      pertinent structures and maximized transoral access. A significant learning curve
      from the first 5 surgical cases to subsequent cases with respect to robot docking
      time was observed (9 vs 3 minutes, respectively; P < .05). Operative time,
      estimated blood loss, and postoperative complication profiles are within the
      expected and acceptable limitations for performing lingual tonsillectomy in the
      pediatric population. CONCLUSIONS AND RELEVANCE: Technologic advances have
      allowed miniaturization of robotic instrumentation and have expanded the scope of
      surgical options for the pediatric airway. Robotic-assisted lingual tonsillectomy
      is well tolerated and can be performed in the pediatric population with excellent
      success. It should be considered a feasible option for implementation at an
      institution-based level.

PMID- 24135746
TI  - No difference in blood loss during endoscopic sinus surgery with total
      intravenous anesthesia?

PMID- 24135745
TI  - Association of exercise with lower long-term risk of olfactory impairment in
      older adults.
AB  - IMPORTANCE: The prevalence of olfactory impairment is high in older adults, and
      this decline in olfactory ability may pose health and safety risks, affect
      nutrition, and decrease quality of life. It is important to identify modifiable
      risk factors to reduce the burden of olfactory impairment in aging populations.
      OBJECTIVE: To determine if exercise is associated with the 10-year cumulative
      incidence of olfactory impairment. DESIGN, SETTING, AND PARTICIPANTS:
      Observational longitudinal population-based Epidemiology of Hearing Loss Study.
      Participants without olfactory impairment (n = 1611) were ages 53 to 97 years at
      baseline and were followed for up to 10 years (1998-2010). MAIN OUTCOMES AND
      MEASURES: Olfaction was measured with the San Diego Odor Identification Test at 3
      examinations (1998-2000, 2003-2005, and 2009-2010) of the Epidemiology of Hearing
      Loss Study. The main outcome was the incidence of olfactory impairment 5 (2003
      2005) or 10 (2009-2010) years later and the association of baseline exercise with
      the long-term risk of developing olfactory impairment. RESULTS: The 10-year
      cumulative incidence of olfactory impairment was 27.6% (95% CI, 25.3%-29.9%) and
      rates varied by age and sex; those who were older (hazard ratio [HR], 1.88 [95%
      CI, 1.74-2.03], for every 5 years) or male (HR, 1.27 [95% CI, 1.00-1.61]) had an
      increased risk of olfactory impairment. Participants who reported exercising at
      least once a week long enough to work up a sweat had a decreased risk of
      olfactory impairment (age- and sex-adjusted HR, 0.76 [95% CI, 0.60-0.97]).
      Increasing frequency of exercise was associated with decreasing risk of
      developing olfactory impairment (P value for trend = .02). CONCLUSIONS AND
      RELEVANCE: Regular exercise was associated with lower 10-year cumulative
      incidence of olfactory impairment. Older adults who exercise may be able to
      retain olfactory function with age.

PMID- 24135747
TI  - No difference in blood loss during endoscopic sinus surgery with total
      intravenous anesthesia--reply.

PMID- 24135750
TI  - Ventromedial PFC, parahippocampal, and cerebellar connectivity are associated
      with temporal discounting in old age.
AB  - Temporal discounting occurs when a greater delayed reward is forsaken for a
      smaller immediate reward, and has been associated with a number of financial and
      health care outcomes important for older adults. Using resting-state fMRI and
      seed regions of interest in the left and right fronto-insular (FI) cortices, we
      explored the neurobiological substrate of temporal discounting in 123 non
      demented older adults from the Rush Memory and Aging Project. For the left FI
      cortex, temporal discounting was positively associated with functional
      connectivity to the right ventromedial prefrontal cortex and middle temporal
      regions, and negatively associated with parahippocampal and right cerebellar
      regions. For the right FI cortex, temporal discounting was negatively associated
      with functional connectivity to a right cerebellar region. Connectivity maps of
      both left and right seed regions of interest overlapped in the right cerebellum.
      Results support the notion of different brain functional connectivity patterns
      associated with the dynamic range of temporal discounting in old age. 

PMID- 24135751
TI  - Bone marrow transplantation transfers age-related susceptibility to neovascular
      remodeling in murine laser-induced choroidal neovascularization.
AB  - PURPOSE: Neovascular remodeling (NVR), the progression of small capillaries into
      large-caliber arterioles with perivascular fibrosis, represents a major
      therapeutic challenge in neovascular age-related macular degeneration (AMD).
      Neovascular remodeling occurs after laser-induced choroidal neovascularization
      (CNV) in aged but not young mice. Additionally, bone marrow-derived cells,
      including macrophages, endothelial precursor cells, and mesenchymal precursor
      cells, contribute to CNV severity. In this study, we investigated the impact of
      aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and
      vascular morphology of CNV lesions in a mouse model of laser-induced CNV.
      METHODS: Young (2 months) and old (16 months) mice were transplanted with green
      fluorescent protein (GFP)-labeled bone marrow isolated from either young or old
      donors. Laser CNV was induced 1 month following transplant, and eyes were
      analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser.
      The identity of cells infiltrating CNV lesions was determined using specific
      markers for the labeled transplanted cells (GFP+), macrophages (F4/80+),
      perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and
      endothelial cells (CD31+). RESULTS: Bone marrow transplantation from aged mice
      transferred susceptibility to NVR into young recipients. Inversely,
      transplantation of young marrow into old mice prevented NVR, preserving small
      size and minimal fibrosis. Mice with NVR demonstrated a greater relative
      contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to
      other cells. CONCLUSIONS: Our findings indicate that the status of bone marrow is
      an important determining factor of neovascular severity. Furthermore, we find
      that perivascular mesenchymal cells, rather than endothelial cells, derived from
      aged bone marrow may contribute to increased CNV severity in this murine model of
      experimental neovascularization.

PMID- 24135752
TI  - Prevalence and types of glaucoma among an indigenous African population in
      southwestern Nigeria.
AB  - PURPOSE: To determine the prevalence and identify the types of glaucoma in the
      Akinyele district of Oyo State in southwestern Nigeria. METHODS: Residents of
      Akinyele district of Oyo State in southwestern Nigeria aged 40 years and older
      were randomly selected in a stratified manner. All participants underwent
      comprehensive ophthalmic examination, including visual acuity assessment,
      anterior segment biomicroscopy, IOP measurement, gonioscopy, optic nerve head and
      disc evaluation, and central visual field assessment. Glaucoma was diagnosed
      using the International Society of Geographical and Epidemiological Ophthalmology
      (ISGEO) classification scheme. RESULTS: A sample of 811 subjects (90% response
      rate) was examined. The crude prevalence of all forms of glaucoma was 7.3% (95%
      confidence interval [CI] 5.5%-9.1%) with an age and sex standardized rate of 6.9%
      (95% CI 6.88%-6.92%). Primary open angle glaucoma was found in 6.2% (95% CI 4.5%
      7.8%) and primary angle closure glaucoma in 0.2% (95% CI 0.0%-0.6%). Secondary
      glaucoma accounted for 0.9% of the cases, with couching and neovascular process
      being the main causes (0.2% each). Prevalence of glaucoma increased significantly
      with increasing age (P for trend < 0.05). CONCLUSIONS: The high prevalence of
      glaucoma (7.3%) in the Akinyele district in southwestern Nigeria is comparable
      with those in predominantly black populations in the Akwapim-South district of
      Ghana and Barbados. Primary open angle glaucoma remains the most prevalent form
      of glaucoma.

PMID- 24135753
TI  - Intrasession test-retest variability of microperimetry in age-related macular
      degeneration.
AB  - PURPOSE: To determine the intrasession test-retest variability of microperimetry
      in participants with age-related macular degeneration (AMD). METHODS: This study
      consisted of two separate groups of subjects who had not performed microperimetry
      previously. In group 1, 30 AMD and 14 control participants performed three
      microperimetry examinations of a selected eye within one session (test 1 and 2,
      first pair; test 2 and 3, second pair). Follow-up examination at 6 months was
      available in 20 AMD participants in group 1, who performed two microperimetry
      examinations. In group 2, 71 AMD participants performed a short practice
      examination, then two microperimetry examinations of the right eye (test 1 and 2,
      first pair) and two of the left eye (test 3 and 4, second pair). RESULTS: There
      was a significant improvement in average point-wise sensitivity (PWS) between the
      first pair of examination in both groups (P < 0.001), but not in the subsequent
      pair (P >= 0.774). This improvement was not observed at the follow-up visit in
      the subset of AMD participants in group 1 (P = 0.433). The PWS coefficient of
      repeatability (CoR) for the second pair of examinations was +/- 4.12 dB and +/-
      4.37 dB for AMD participants for group 1 and 2 respectively. CONCLUSIONS: A
      significant increase in sensitivity between the first and second test, but not in
      the subsequent tests, was found for participants who had not performed
      microperimetry previously. Intrasession test-retest variability can therefore be
      minimized by discarding the first examination to avoid the influence of a
      learning effect.

PMID- 24135754
TI  - A comparison of patient matched meibum and tear lipidomes.
AB  - PURPOSE: To quantify the molecular lipid composition of patient-matched tear and
      meibum samples and compare tear and meibum lipid molecular profiles. METHODS:
      Lipids were extracted from tears and meibum by bi-phasic methods using 10:3 tert
      butyl methyl ether:methanol, washed with aqueous ammonium acetate, and analyzed
      by chip-based nanoelectrospray ionization tandem mass spectrometry. Targeted
      precursor ion and neutral loss scans identified individual molecular lipids and
      quantification was obtained by comparison to internal standards in each lipid
      class. RESULTS: Two hundred and thirty-six lipid species were identified and
      quantified from nine lipid classes comprised of cholesterol esters, wax esters,
      (O-acyl)-omega-hydroxy fatty acids, triacylglycerols, phosphatidylcholine,
      lysophosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and
      phosphatidylserine. With the exception of phospholipids, lipid molecular profiles
      were strikingly similar between tears and meibum. CONCLUSIONS: Comparisons
      between tears and meibum indicate that meibum is likely to supply the majority of
      lipids in the tear film lipid layer. However, the observed higher mole ratio of
      phospholipid in tears shows that analysis of meibum alone does not provide a
      complete understanding of the tear film lipid composition.

PMID- 24135756
TI  - Collagen XVIII short isoform is critical for retinal vascularization, and
      overexpression of the Tsp-1 domain affects eye growth and cataract formation.
AB  - PURPOSE: Collagen XVIII deficiency leads to anterior and posterior eye defects in
      Col18a1(-/-) mice, and overexpression of its C-terminal endostatin domain under a
      K14 promoter leads to cataract. We studied the consequences of K14-driven
      overexpression of the thrombospondin-1 (Tsp-1)-like domain, and also the roles of
      the three collagen XVIII isoforms in mice specifically lacking either the
      promoter 1-derived short or the promoter 2-derived medium/long isoforms. METHODS:
      Two transgenic lines were generated and compared to Col18a1(-/-) and promoter 1
      and 2 knockouts. Enucleated eyes were analyzed histopathologically,
      immunohistochemically, biochemically, and ultrastructurally. IOP was measured by
      noninvasive tonometry, and the anterior chamber was studied in vivo using a slit
      lamp and optical coherence tomography. RESULTS: Overexpression of the Tsp-1
      transgene in an FVB/N background resulted in increased axial length, and
      substantial incidences of cataract, lens subluxation, phthisis, retinal ablation,
      corneal vascularization, and intraocular hemorrhages. The FVB/N Col18a1(-/-) mice
      were affected similarly. The findings in the knockout and transgenic lines were
      milder in a C57BL/6JOlaHsd (B6) background. Studies with the promoter-specific
      knockouts revealed the short isoform as the sole variant in the lens capsule and
      inner limiting membrane, while the ciliary body, iris, and Bruch's membrane
      contained short and medium/long isoforms. Lack of the short isoform, but not of
      the medium/long isoforms, caused aberrant retinal vascularization. CONCLUSIONS:
      An excess of the collagen XVIII Tsp-1 domain is deleterious in the eye, possibly
      by impairing certain functions of the full-length molecule. Moreover, the short
      isoform is the critical variant in the development of the posterior eye
      structures.

PMID- 24135755
TI  - Cone structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes
      with nonneovascular age-related macular degeneration.
AB  - PURPOSE: To evaluate cone spacing using adaptive optics scanning laser
      ophthalmoscopy (AOSLO) in eyes with nonneovascular AMD, and to correlate
      progression of AOSLO-derived cone measures with standard measures of macular
      structure. METHODS: Adaptive optics scanning laser ophthalmoscopy images were
      obtained over 12 to 21 months from seven patients with AMD including four eyes
      with geographic atrophy (GA) and four eyes with drusen. Adaptive optics scanning
      laser ophthalmoscopy images were overlaid with color, infrared, and
      autofluorescence fundus photographs and spectral domain optical coherence
      tomography (SD-OCT) images to allow direct correlation of cone parameters with
      macular structure. Cone spacing was measured for each visit in selected regions
      including areas over drusen (n = 29), at GA margins (n = 14), and regions without
      drusen or GA (n = 13) and compared with normal, age-similar values. RESULTS:
      Adaptive optics scanning laser ophthalmoscopy imaging revealed continuous cone
      mosaics up to the GA edge and overlying drusen, although reduced cone
      reflectivity often resulted in hyporeflective AOSLO signals at these locations.
      Baseline cone spacing measures were normal in 13/13 unaffected regions, 26/28
      drusen regions, and 12/14 GA margin regions. Although standard clinical measures
      showed progression of GA in all study eyes, cone spacing remained within normal
      ranges in most drusen regions and all GA margin regions. CONCLUSIONS: Adaptive
      optics scanning laser ophthalmoscopy provides adequate resolution for
      quantitative measurement of cone spacing at the margin of GA and over drusen in
      eyes with AMD. Although cone spacing was often normal at baseline and remained
      normal over time, these regions showed focal areas of decreased cone
      reflectivity. These findings may provide insight into the pathophysiology of AMD
      progression. (ClinicalTrials.gov number, NCT00254605).

PMID- 24135757
TI  - Retinal nerve fiber layer structure abnormalities in schizophrenia and its
      relationship to disease state: evidence from optical coherence tomography.
AB  - PURPOSE: We determined structural retinal nerve fiber layer (RNFL) changes in
      schizophrenia patients and established if the structural changes were related to
      the duration of the illness using spectral-domain optical coherence tomography
      (SD-OCT). METHODS: We recruited a total of 30 schizophrenic patients and 30 age
      matched controls in the study. The schizophrenic patients were subdivided further
      to acute (n = 5), chronic (n = 13), and long-term chronic (n = 12) subgroups
      depending on their duration of illness. Using SD-OCT, the peripapillary RNFL
      thickness, macula thickness, and macula volume measurements of schizophrenic
      patients and the control subjects were measured and compared at each location.
      RESULTS: Schizophrenic patients showed a statistically significant reduction in
      overall peripapillary RNFL thickness (cases, 94.70 +/- 9.88 MUm; controls, 103.53
      +/- 6.53 MUm; P < 0.001), macula thickness (cases, 269.26 +/- 12.59 MUm;
      controls, 284.83 +/- 9.76 MUm; P < 0.001), and macula volume (cases, 9.61 +/-
      0.45 mm(3); controls, 10.17 +/- 0.35 MUm; P < 0.001). Chronic and long-term
      chronic schizophrenic patients were found to have significant peripapillary RNFL
      thinning, macula thinning, and reduction of macula volume when compared to
      controls (P < 0.001). There also was a statistically significant reverse
      correlation (P < 0.05) of peripapillary RNFL thickness (r = -0.36), macula
      thickness (r = -0.38), and macula volume reduction (r = -0.36) with the duration
      of schizophrenic illness. CONCLUSIONS: These results indicate that RNFL and
      macula thickness, as well as macula volume measurements are reduced in
      schizophrenic patients. The degree of thinning and reduction was more significant
      in the chronic phase of the disease and correlated with the duration of illness.
      These findings demonstrate that SD-OCT can be a useful tool for the diagnosis and
      monitoring the progression of this disease.

PMID- 24135758
TI  - The locations of circumpapillary glaucomatous defects seen on frequency-domain
      OCT scans.
AB  - PURPOSE: To examine the locations of local glaucomatous damage around the optic
      disc as seen in the circumpapillary retinal nerve fiber layer (RNFL) on frequency
      domain optical coherence tomography (fdOCT). METHODS: Optic disc fdOCT volume
      scans from 54 healthy control eyes and 114 patient eyes, classified as suspected
      or mild glaucoma, were analyzed. All patient eyes had 24-2 visual fields (VFs)
      with mean deviations better than -5.5 dB. By hand-correcting automated
      segmentation, the RNFL thickness profile was obtained for a circumpapillary
      circle. RNFL defects were defined as regions where the patient's RNFL thickness
      fell below the 99% confidence limit of control values. The location of a defect
      was defined as the point of greatest difference between the patient's thickness
      and the 99% limit. The locations of major blood vessels (BVs) were marked, and
      separated into superior-nasal (SN), superior-temporal (ST), inferior-temporal
      (IT), and inferior-nasal (IN) groups. RESULTS: Of the 114 patient eyes, 45
      exhibited a total of 75 RNFL defects. The locations of these defects clustered
      around the ST, SN, and IT, but not the IN BVs. CONCLUSIONS: The absence of
      defects in the IN region indicates that the locations of local defects are not
      simply related to either BV location or RNFL thickness. The local defects in the
      ST and IT regions can be related to arcuate defects seen on 24-2 and 10-2 VFs.
      However, the defects in the SN region suggest the presence of VF defects that may
      be overlooked because they fall largely outside the 24-2 test grid.

PMID- 24135759
TI  - Orbital fibroblasts from thyroid eye disease patients differ in proliferative and
      adipogenic responses depending on disease subtype.
AB  - PURPOSE: Thyroid eye disease (TED) patients are classified as type I
      (predominantly fat compartment enlargement) or type II (predominantly extraocular
      muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be
      driven to proliferate or differentiate into adipocytes in vitro. We tested the
      hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas
      type II OFs proliferate more than type I OFs. We also examined the effect of
      cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. METHODS:
      Type I, type II, and non-TED OFs were treated with transforming growth factor
      beta (TGFbeta) to induce proliferation and with 15-deoxy-Delta(-12,14)
      prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured
      using the [(3)H]thymidine assay, and adipogenesis was measured using the AdipoRed
      assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on
      adipogenesis and proliferation was also studied. RESULTS: Type II OFs
      incorporated 1.7-fold more [(3)H]thymidine than type I OFs (P < 0.05). Type I OFs
      accumulated 4.8-fold more lipid than type II OFs (P < 0.05) and 12.6-fold more
      lipid than non-TED OFs (P < 0.05). Oil Red O staining and flow cytometry also
      demonstrated increased adipogenesis in type I OFs compared to type II and non-TED
      OFs. Cyclooxygenase inhibition significantly decreased proliferation and
      adipogenesis in type II OFs, but not type I OFs. CONCLUSIONS: We have
      demonstrated that OFs from TED patients have heterogeneous responses to
      proproliferative and proadipogenic stimulators in vitro in a manner that
      corresponds to their different clinical manifestations. Furthermore, we
      demonstrated a differential effect of COX inhibitors on type I and type II OF
      proliferation and adipogenesis.

PMID- 24135760
TI  - Relationship between retinal vascular geometry with retinal nerve fiber layer and
      ganglion cell-inner plexiform layer in nonglaucomatous eyes.
AB  - PURPOSE: To examine the relationship between retinal vascular geometric
      parameters with retinal nerve fiber layer (RNFL) and ganglion cell-inner
      plexiform layer (GC-IPL) parameters in nonglaucomatous subjects. METHODS: Study
      subjects were identified from the Singapore Chinese Eye Study (SCES), a
      population-based survey of Singaporean Chinese aged 40 to 80 years. All subjects
      underwent standardized systemic and ocular examinations. Nonglaucomatous eyes
      were defined as eyes with normal, reliable visual field results. Retinal vascular
      parameters (retinal vascular fractal dimension, tortuosity, and caliber) were
      measured from retinal photographs by using a computer-assisted program, according
      to a standardized protocol. Spectral-domain optical coherence tomography (SD-OCT)
      was used to measure RNFL and macular GC-IPL thicknesses. RESULTS: A total of 352
      nonglaucomatous subjects with gradable retinal photographs and OCT images were
      included for the final analyses. In multiple regression analyses, after adjusting
      for age, sex, hypertension, diabetes, axial length, disc area, and OCT signal
      strength; decreased retinal vascular fractal dimension (beta = -1.60, P = 0.002),
      narrower retinal arteriolar caliber (beta = -1.60, P = 0.001), and venular
      caliber (beta = -1.97, P < 0.001) were independently associated with thinner
      average RNFL thickness. In addition, decreased retinal vascular fractal dimension
      (beta = -0.77, P = 0.017) and decreased retinal venular tortuosity (beta = -0.63,
      P = 0.042) were independently associated with thinner average GC-IPL thickness
      after adjusting for age, sex, hypertension, diabetes, axial length, and OCT
      signal strength. CONCLUSIONS: Rarefaction, vasoconstriction, and straightening of
      the retinal vasculature are associated with thinner RNFL and GC-IPL thickness.
      This information may potentially provide further insights on the role of vascular
      processes in glaucoma development and progression.

PMID- 24135761
TI  - Survival rates for goblet cell carcinoma of the appendix.

PMID- 24135762
TI  - Congenital superior-inferior mesenteric arterial variation or arc of Riolan due
      to occlusion of proximal superior mesenteric artery.

PMID- 24135763
TI  - Reflections about the cranial nerves destinated to the face: plea for a global
      approach including nerves and their branches, canals, vessels, distribution and
      clinical relevance.

PMID- 24135764
TI  - Prospective evaluation of a prenatal sonographic clubfoot classification system.
AB  - BACKGROUND: The purpose of this study was to prospectively evaluate our recently
      described fetal sonographic classification system for prenatal diagnosis of
      clubfoot. METHODS: Over 18 months, we prospectively enrolled consecutive pregnant
      patients evaluated for a prenatally diagnosed clubfoot. Prenatal sonographic
      scores assigned by a radiologist were compared to final clinical diagnosis and
      severity given by a pediatric orthopedic surgeon. Pearson's chi(2) test and
      logistic regression were used in statistical analyses on the subject level.
      Generalized estimating equations were used in analyses on the foot level to
      account for intrasubject correlation. RESULTS: There were 50 subjects, with 26
      unilateral and 24 bilateral clubfeet, according to the prenatal ultrasound (US).
      A total of 51 (69%) of 74 feet and 36 (72%) of 50 subjects had a postnatal
      diagnosis of clubfoot. The accuracy of diagnosis in cases of a severe, moderate,
      and mild US score was 94, 70, and 25%, respectively (p = 0.003 comparing moderate
      severe vs. mild). US severity correlated with the Dimeglio classification scoring
      system (Spearman's correlation 0.30). CONCLUSION: The fetal sonographic scoring
      system is predictive of clinical severity after birth, and improves the ability
      to counsel families with a prenatal diagnosis of clubfoot.

PMID- 24135765
TI  - Highly correlated stimuli do not necessarily facilitate the measurement of
      unconscious perception: exclusion failure is hard to find in forced-choice tasks.
AB  - Persaud and McLeod (2008) report that unconscious perception is easier to measure
      with forced-choice exclusion tasks when the stimuli are highly similar, such as
      choosing between the letters 'h' and 'b'. The high degree of stimulus similarity
      may decrease conscious awareness of the target stimuli while leaving unconscious
      cognition intact. The present experiments used forced-choice exclusion tasks
      (i.e., choosing the opposite of a masked target stimulus) with the aim of
      replicating these findings. No evidence of relevant perception - either conscious
      or unconscious - was obtained with short duration targets. The forced-choice
      exclusion task was correctly performed at longer target durations (25 ms and
      higher), which suggests conscious perception of the target stimuli. We conclude
      that increasing stimulus similarity does not reliably produce exclusion failure
      effects and does not appear to facilitate the measurement of unconscious
      cognition.

PMID- 24135766
TI  - Prolonged clinical benefit from the maintenance hormone therapy in patients with
      metastatic breast cancer.
AB  - OBJECTIVE: We investigated the efficacy of maintenance hormone therapy (MHT),
      which was given to hormone positive metastatic breast cancer (MBC) patients in
      non-progression status to the previous chemotherapy. METHODS: This study
      retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006
      to 2010 at a single institute. RESULTS: For the 76 patients reviewed, the median
      progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6-17.3).
      Prolonged PFS was associated with less previous palliative chemotherapy, fewer
      metastatic sites, and the absence of visceral metastasis in univariate analysis.
      Multivariate analysis showed that only the number of previous palliative
      chemotherapy (HR 1.73, 95% CI, 1.00-2.98; P = 0.04) remained as a significant
      variable. MHT was generally well tolerated. CONCLUSIONS: MHT showed considerable
      efficacy and tolerability in this study. Further randomized prospective study is
      warranted.

PMID- 24135767
TI  - Sentinel node and occult lesion localization (SNOLL): a systematic review.
AB  - BACKGROUND: Sentinel node and occult lesion localization (SNOLL) is an
      alternative to wire-guided localization (WGL) for guiding surgical excision of
      non-palpable breast cancer and the performance of concurrent sentinel lymph node
      biopsy (SLNB). This review provides an overview of the available evidence on the
      accuracy of SNOLL in patients undergoing breast-conserving surgery. METHODS:
      PubMed, Embase and the Cochrane Library were searched systematically in April
      2013 for studies that address localization of non-palpable breast cancer using
      SNOLL. Studies were deemed eligible if they reported on the proportion of
      patients with tumour-positive margins, re-operation rates, performance of
      concurrent SLNB and considered non-palpable malignant disease only (invasive and
      in situ) in SNOLL. RESULTS: Seven studies reported data on SNOLL in 983 patients
      with non-palpable breast cancers. Overall complete resection rates ranged from 82
      to 90.5 per cent. Second operation rates ranged between 2 and 12 per cent and
      SLNB success rates between 88.2 and 100 per cent. The risk of failed surgical
      localization was between 0 and 4.5 per cent in the studies. CONCLUSION: Available
      scientific evidence suggests that SNOLL is a safe and accurate technique for the
      localization of non-palpable breast cancers.

PMID- 24135769
TI  - Onset-related differences in neural substrates of tinnitus-related distress: the
      anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early
      onset tinnitus.
AB  - Recent findings regarding differences in tinnitus-related neural activity
      according to onset age have raised a question on possible onset age-related
      differences in neural substrates of distress. Hence we collected quantitative
      electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29
      early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively)
      participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were
      then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress
      (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT
      group, the LOT group demonstrated increased qEEG source-localized activity and
      functional connectivity primarily in the anterior cingulate cortex (ACC) and
      parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT
      participants than in LD-LOT participants for the beta 1, beta 2 and gamma
      frequency bands, while the left orbitofrontal cortex and left dorsolateral
      prefrontal cortex were activated more in HD-EOT than in LD-EOT for the delta/beta
      and gamma frequency bands, respectively. Even with the same amount of tinnitus
      related distress level, responsible neural substrates are different according to
      the onset age. These differences may be important for exploring different target
      areas of treatment according to tinnitus onset age, as well as for conducting
      similar studies on other pathologies, such as depression or pain.

PMID- 24135768
TI  - Effect of isoniazid therapy for latent TB infection on QuantiFERON-TB gold in
      tube responses in adults with positive tuberculin skin test results in a high TB
      incidence area: a controlled study.
AB  - BACKGROUND: T-cell interferon-gamma release assays (IGRAs) are used in the
      diagnosis of Mycobacterium tuberculosis infection and could be useful biomarkers
      of response to treatment of latent TB infection for clinical trials, infection
      control units, and TB programs. METHODS: This investigation was a prospective,
      controlled substudy of IGRA responses in 82 healthy South African adults with HIV
      seronegative and positive tuberculin skin test results randomly assigned to
      treatment with 6 months of daily isoniazid preventive therapy (IPT) or
      observation before Bacillus Calmette-Guerin revaccination in a clinical trial.
      QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was used to measure interferon-gamma
      (IFN-gamma) response to mycobacterial antigens at baseline and after IPT or
      observation. RESULTS: IFN-gamma levels declined between baseline and the end of
      IPT (signed rank test P<=.0001) and between baseline and a similar period of
      observation without IPT (signed rank test P=.03). The rate of decrease in IFN
      gamma responses over time did not differ between the groups (Mann-Whitney
      Wilcoxon test P=.31). QFT-GIT test results in two subjects (5%) in the IPT group
      and two subjects (5%) in the observation group reverted from positive to negative
      during follow-up. No significant difference was found between the groups with
      respect to baseline positivity or the proportion of patients whose tests reverted
      to negative. CONCLUSIONS: IPT had no effect on changes in QFT-GIT readouts during
      short-term follow-up of adults with positive tuberculin skin tests in a high TB
      incidence setting. QFT-GIT is unlikely to be a useful biomarker of response to
      treatment of latent TB infection. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01119521; URL: www.clinicaltrials.gov.

PMID- 24135770
TI  - Action selection in a possible model of striatal medium spiny neuron dysfunction:
      behavioral and EEG data in a patient with benign hereditary chorea.
AB  - Chaining or cascading of different actions and responses is necessary to
      accomplish a goal. Yet, little is known about the functional neuroanatomical
      electrophysiological mechanisms mediating these processes. Computational models
      suggest that medium spiny neurons (MSNs) play an important role in action
      cascading, but this assumption has hardly been tested relating neuroanatomical
      and electrophysiological parameters in a human model of circumscribed MSN
      dysfunction. As a possible human model of circumscribed MSN dysfunction, we
      investigate benign hereditary chorea in a case-control study applying bootstrap
      statistics. To investigate these mechanisms, we used a stop-change paradigm,
      where we apply mathematical constraints to describe the degree of how task goals
      are activated with more or less overlap during action cascading. We record event
      related potentials and analyze neural synchronization processes. The results show
      that MSN dysfunctions lead to deficits in action cascading processes only when
      two response options seek simultaneous access to response selection resources.
      Attentional selection processes are not affected, but processes reflecting the
      transition between stimulus evaluation and responding are affected. The results
      underline computational models of MSN functioning and show that dysfunction in
      these networks leads to a more parallel and hence inefficient response selection.

PMID- 24135771
TI  - Effects of postnatal hyperoxia exposure on the rat dentate gyrus and
      subventricular zone.
AB  - Premature newborns may be exposed to hyperoxia in the first postnatal period, but
      clinical and experimental works have raised the question of oxygen toxicity for
      the developing brain. However, specific analysis of hyperoxia exposure on
      neurogenesis is still lacking. Thus, the aim of the present study was to evaluate
      possible changes in the morphometric parameters of the main neurogenic sites in
      newborn rats exposed to 60 or 95 % oxygen for the first 14 postnatal days. The
      optical disector, a morphometric method based upon unbiased sampling principles
      of stereology, was applied to analyse cell densities, total volumes, and total
      cell numbers of the dentate gyrus (DG) and subventricular zone (SVZ). Apoptosis
      and proliferation were also studied by terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labelling method and anti-ki67 immunohistochemistry,
      respectively. Severe hyperoxia increased the percentage of apoptotic cells in the
      DG. Moderate and severe hyperoxia induced a proliferative response both in the DG
      and SVZ, but the two neurogenic sites showed different changes in their
      morphometric parameters. The DG of both the hyperoxic groups showed lower volume
      and total cell number than that of the normoxic one. Conversely, the SVZ of
      newborn rats exposed to 95 % hyperoxia showed statistically significant higher
      volume and total cell number than SVZ of rats raised in normoxia. Our findings
      indicate that hyperoxia exposure in the first postnatal period affects both the
      neurogenic areas, although in different ways, i.e. reduction of DG and expansion
      of SVZ.

PMID- 24135772
TI  - alpha-Synuclein in the olfactory system in Parkinson's disease: role of neural
      connections on spreading pathology.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by
      bradykinesia, rigidity, resting tremor, and postural instability.
      Neuropathologically, intracellular aggregates of alpha-synuclein in Lewy bodies
      and Lewy neurites appear in particular brain areas according to a sequence of
      stages. Clinical diagnosis is usually established when motor symptoms are evident
      (corresponding to Braak stage III or later), years or even decades after onset of
      the disease. Research at early stages is therefore essential to understand the
      etiology of PD and improve treatment. Although classically considered as a motor
      disease, non-motor symptoms have recently gained interest. Olfactory deficits are
      among the earliest non-motor features of PD. Interestingly, alpha-synuclein
      deposits are present in the olfactory bulb and anterior olfactory nucleus at
      Braak stage I. Several lines of evidence have led to proposals that PD pathology
      spreads by a prion-like mechanism via the olfactory and vagal systems to the
      substantia nigra. In this context, current data on the temporal appearance of
      alpha-synuclein aggregates in the olfactory system of both humans and transgenic
      mice are of particular relevance. In addition to the proposed retrograde nigral
      involvement via brainstem nuclei, olfactory pathways could potentially reach the
      substantia nigra, and the possibility of centrifugal progression warrants
      investigation. This review analyzes the involvement of alpha-synuclein in
      different elements of the olfactory system, in both humans and transgenic models,
      from the hodological perspective of possible anterograde and/or retrograde
      progression of this proteinopathy within the olfactory system and beyond-to the
      substantia nigra and the remainder of the central and peripheral nervous systems.

PMID- 24135773
TI  - Shifted neuronal balance during stimulus-response integration in schizophrenia:
      an fMRI study.
AB  - Schizophrenia is characterized by marked deficits in executive and psychomotor
      functions, as demonstrated for goal-directed actions in the antisaccade task.
      Recent studies, however, suggest that this deficit represents only one
      manifestation of a general deficit in stimulus-response integration and
      volitional initiation of motor responses. We here used functional magnetic
      resonance imaging to investigate brain activation patterns during a manual
      stimulus-response compatibility task in 18 schizophrenic patients and 18
      controls. We found that across groups incongruent vs. congruent responses
      recruited a bilateral network consisting of dorsal fronto-parietal circuits as
      well as bilateral anterior insula, dorsolateral prefrontal cortex (DLPFC) and the
      presupplementary motor area (preSMA). When testing for the main-effect across all
      conditions, patients showed significantly lower activation of the right DLPFC
      and, in turn, increased activation in a left hemispheric network including
      parietal and premotor areas as well as the preSMA. For incongruent responses
      patients showed significantly increased activation in a similar left hemispheric
      network, as well as additional activation in parietal and premotor regions in the
      right hemisphere. The present study reveals that hypoactivity in the right DLPFC
      in schizophrenic patients is accompanied by hyperactivity in several fronto
      parietal regions associated with task execution. Impaired top-down control due to
      a dysfunctional DLPFC might thus be partly compensated by an up-regulation of
      task-relevant regions in schizophrenic patients.

PMID- 24135774
TI  - Biomechanical and histological evaluation of four different titanium implant
      surface modifications: an experimental study in the rabbit tibia.
AB  - OBJECTIVES: This study presents a biomechanical comparison of bone response to
      commercially pure titanium screws with four different types of surface
      topographies placed in the tibial metaphysis of 30 rabbits. MATERIALS AND
      METHODS: One hundred twenty implants were tested double-blinded: (a) blasted,
      acid-etched, and discrete crystal deposition (DCD), (b) blasted, (c) acid-etched,
      and (d) blasted and acid-etch. Resonance frequency analysis (RFA/ISQ), reverse
      torque values (RTV), and bone-to-implant contact (BIC) were measured at the time
      of implant insertion (day 0), 15, 28, and 56 days of healing. RESULTS: All groups
      tested demonstrated increased RFA/ISQ and RTV results over the time course. At 15
      days, the blasted, acid-etched, and DCD group demonstrated a non-significant
      trend toward higher values when compared to the blasted and etched group (33.0 +/
      16 vs. 26.3 +/- 12 Ncm, p = .16). At 56 days, the groups utilizing blasting to
      create additional surface roughness (Sa > 1 micron) showed a statistical
      significant difference in RTQ versus the non-blasted group (38.5 +/- 14 vs. 29.5
      +/- 9 Ncm, p = .03). CONCLUSIONS: Within the limitations of this study, only the
      increase in surface roughness (Ra > 1) at 56 days demonstrated statistically
      significant effects on RTQ. Other additional surface features, such as sub-micron
      scale DCD, demonstrated improved healing trends but without significance for
      clinical applications.

PMID- 24135775
TI  - Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer
      from mother to infant in utero, but only efavirenz transfers via breastfeeding.
AB  - BACKGROUND: As efforts intensify to eliminate perinatal HIV transmission,
      understanding kinetics of maternal-to-child transfer of antiretrovirals during
      pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord
      blood, and breastmilk reflect exposure over short intervals. Hair concentrations
      reflect cumulative exposure and can uniquely quantify in utero transfer of
      maternal medications to infants. We measured plasma and hair antiretroviral
      levels in HIV-infected Ugandan mothers and their infants at delivery and during
      breastfeeding to assess transfer. METHODS: HIV-infected pregnant women were
      randomized to lopinavir/ritonavir- or efavirenz-based therapy in a larger trial
      (the Prevention of Malaria and HIV disease in Tororo, PROMOTE). At 0, 8, and 12
      weeks postpartum, plasma antiretroviral levels were measured in 117 mother-infant
      pairs; hair levels were assayed at 12 weeks. Ratios and correlations of
      infant:maternal concentrations were calculated. RESULTS: By 12 weeks, 90.4% of
      mothers reported exclusive breastfeeding. Hair and plasma levels over time
      suggest moderate (47%) to extensive (87%) in utero transfer of lopinavir and
      ritonavir, respectively, but negligible transfer of either via breastfeeding.
      Moderate transfer of efavirenz occurs during pregnancy and breastfeeding (40%
      cumulative; 15% during breastfeeding). Despite differences in exposure, no infant
      seroconversions or correlations between infant hair/plasma antiretroviral levels
      and adverse effects were observed. CONCLUSIONS: Using a unique approach combining
      hair and plasma data, we found that different antiretrovirals have distinct
      kinetics of mother-to-infant transfer. Efavirenz transfers during both pregnancy
      and breastfeeding, whereas lopinavir and ritonavir transfer only in utero.
      Further study of the degree and timing of maternal-to-child transfer by
      antiretroviral will help optimize strategies that protect infants and minimize
      toxicities during periods of risk.

PMID- 24135776
TI  - A brief and feasible paper-based method to screen for neurocognitive impairment
      in HIV-infected patients: the NEU screen.
AB  - OBJECTIVE: Practical screening methods are necessary to detect neurocognitive
      impairment (NCI) in HIV-infected patients. We aimed to find a brief and feasible
      paper-based tool to facilitate the diagnosis of an HIV-associated neurocognitive
      disorder. METHODS: A total of 106 HIV-infected outpatients with variable clinical
      characteristics were recruited in a multicenter investigation. NCI was diagnosed
      using a standardized neuropsychological tests battery (7 areas, 21 measures, ~2
      hours). Multiple score combinations were compared to find a paper-based method
      that took <=10 minutes to apply. The presence of NCI was considered the gold
      standard for comparisons, and the sensitivity and specificity were calculated.
      RESULTS: Subjects were mostly middle-aged (median, 44 years) men (87%) on
      antiretroviral treatment. NCI was detected in 51 individuals (48%) and was
      associated with lower nadir CD4 count (P < 0.001), receiving antiretroviral
      therapy (P = 0.004), fewer years of education (P = 0.009), and presence of
      comorbidities (P < 0.001). The score combination that showed the highest
      sensitivity (74.5%) and specificity (81.8%) detecting NCI included 3 measures of
      attention/working memory, executive functioning, and verbal fluency (part A of
      Trail Making Test, part B of Trail Making Test, and Controlled Oral Word
      Association Test scores). A broader paper-based selection of measures covering 7
      areas indicated a sensitivity of 100% and a specificity of 96.3% (7 measures, ~35
      minutes). CONCLUSIONS: The combination of the 3 measures presented in this study
      seems to be a rapid and feasible screening mean for NCI in HIV-infected patients.
      This approach, combined with screening for potential comorbidities and daily
      functioning interference, could help in the initial stages of a HIV-associated
      neurocognitive disorder diagnosis and in settings with limited access to
      neuropsychological resources.

PMID- 24135778
TI  - Dual therapy with lamivudine + protease inhibitor during pregnancy for prevention
      of mother-to-child transmission of HIV-1.

PMID- 24135777
TI  - HIV-1 disease progression during highly active antiretroviral therapy: an
      application using population-level data in British Columbia: 1996-2011.
AB  - BACKGROUND: Accurately estimating rates of disease progression is of central
      importance in developing mathematical models used to project outcomes and guide
      resource allocation decisions. Our objective was to specify a multivariate
      regression model to estimate changes in disease progression among individuals on
      highly active antiretroviral treatment in British Columbia, Canada, 1996-2011.
      METHODS: We used population-level data on disease progression and antiretroviral
      treatment utilization from the BC HIV Drug Treatment Program. Disease progression
      was captured using longitudinal CD4 and plasma viral load testing data, linked
      with data on antiretroviral treatment. The study outcome was categorized into
      (CD4 count >= 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state
      continuous-time Markov model was used to estimate covariate-specific
      probabilities of CD4 progression, focusing on temporal changes during the study
      period. RESULTS: A total of 210,083 CD4 measurements among 7421 individuals with
      HIV/AIDS were included in the study. Results of the multivariate model suggested
      that current highly active antiretroviral treatment at baseline, lower baseline
      CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were
      each associated with accelerated progression. Immunological improvement was
      accelerated significantly from 2004 onward, with 23% and 46% increases in the
      probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004
      2008 and 2008-2011, respectively. CONCLUSION: Our results demonstrate the impact
      of innovations in antiretroviral treatment and treatment delivery at the
      population level. These results can be used to estimate a transition probability
      matrix flexible to changes in the observed mix of clients in different clinical
      stages and treatment regimens over time.

PMID- 24135779
TI  - Invasive cervical cancer risk among HIV-infected women is a function of CD4 count
      and screening.

PMID- 24135780
TI  - Is the level of proof of the North American multicohort collaboration prospective
      study sufficient to conclude that incidence of invasive cervical cancer is higher
      in HIV-infected women?

PMID- 24135781
TI  - Increasing frequency of self-reported orogenital HIV-1 transmission among men
      having sex with men: The ANRS PRIMO Cohort.

PMID- 24135782
TI  - Homophobia as a barrier to HIV prevention service access for young men who have
      sex with men.

PMID- 24135783
TI  - Measurements of short distances between trityl spin labels with CW EPR, DQC and
      PELDOR.
AB  - Trityl based spin labels are emerging as a complement to nitroxides in nanometer
      distance measurements using EPR methods. The narrow spectral width of the trityl
      radicals prompts us to ask the question at which distance between these spin
      centers, the pseudo-secular part of the dipolar coupling and spin density
      delocalization have to be taken into account. For this, two trityl-trityl and one
      trityl-nitroxide model compounds were synthesized with well-defined interspin
      distances. Continuous wave (CW) EPR, double quantum coherence (DQC) and pulsed
      electron-electron double resonance (PELDOR) spectra were acquired from these
      compounds at commercial X-band frequencies. The data analysis shows that two of
      the compounds, with distances of up to 25 A, fall into the strong coupling regime
      and that precise distances can only be obtained if both the spin density
      delocalization and the pseudo-secular part of the dipolar coupling are included
      in the analysis. 

PMID- 24135784
TI  - Changes in circulating red cell volume during the first 6 weeks of life in very
      low-birth-weight infants.
AB  - BACKGROUND: Little is known about the change in circulating red cell volume (RCV)
      of very-low-birth-weight (VLBW) infants during the first weeks of life. METHODS:
      RCV was measured during the first 5 d in 35 VLBW infants using chromium-51
      labeling of the infants' red blood cells (RBCs). RCV was measured again at 6 wk
      of age in 12 infants, and the volumes of RBCs lost by phlebotomy and those gained
      by transfusion were recorded between the RCV measurements. In six infants, the
      volume of waste blood on materials contaminated with blood during phlebotomy,
      which would usually be discarded, was measured by radioactive counting. RESULTS:
      The mean RCV in the first several days of life was 39.6 ml (35.7 ml/kg; range:
      20.1-58.7 ml/kg). Of the 12 infants whose RCV was measured twice, all but one had
      a decrease in absolute RCV. The mean RCV initially and at 6 wk were 37.3 and 26.6
      ml, respectively. The mean volume of RBCs lost through phlebotomy was 29.2 ml,
      and the mean volume of RBCs given by transfusion was 34.5 ml. CONCLUSION: During
      the first 6 wk of life, when the anemia of prematurity is evolving, the RCV falls
      despite complete replacement of RBCs lost by diagnostic phlebotomy with
      transfused RBCs.

PMID- 24135785
TI  - Lipopolysaccharide and soluble CD14 in cord blood plasma are associated with
      prematurity and chorioamnionitis.
AB  - BACKGROUND: Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria,
      causes preterm birth in animals and has been implicated as a factor triggering
      preterm labor and systemic complications in humans. Little is known regarding LPS
      in the cord blood (CB) of term and preterm infants and its association with
      maternal and fetal characteristics. METHODS: CB was obtained from term (n = 15)
      and preterm infants (n = 76) after delivery. Plasma levels of LPS, C-reactive
      protein (CRP), and soluble CD14 (sCD14) were measured using commercially
      available kits (limulus amebocyte lysate and enzyme-linked immunosorbent assay).
      Four linear regression models were created in order to identify independent
      variables that predict plasma LPS levels. RESULTS: The analyte levels were
      significantly higher in preterm vs. term infant CB: LPS (24.48 vs. 1 pg/ml; P =
      0.0009), CRP (87.9 vs. 47 ng/ml; P = 0.01), and sCD14 (0.32 vs.0.35 ug/ml; P =
      0.013). There was a (significant) positive correlation between CB LPS levels and
      gestational age, birth weight, CRP levels, sCD14 levels, and association with
      both clinical and histological chorioamnionitis. CONCLUSION: Our data suggest
      that LPS is associated with preterm labor and inflammation (CRP elevation and
      chorioamnionitis). These findings may be relevant to the understanding of the
      role of LPS in prematurity and its role in preterm morbidities.

PMID- 24135787
TI  - Mild cognitive impairment: clinical and imaging profile in a memory clinic
      setting in India.
AB  - BACKGROUND: Despite the increasing burden of dementia in developing countries,
      mild cognitive impairment (MCI) continues to be underexplored. MCI has
      conventionally been identified based on clinical profile, but recently,
      biomarkers suggestive of Alzheimer's disease pathology have been included in the
      revised National Institute on Aging and the Alzheimer's Association (NIA-AA)
      criteria. In this study, we evaluated the profile of MCI in a memory clinic in
      India and explored the applicability of the revised NIA-AA criteria in a limited
      resource setting. METHODS: Consecutive subjects evaluated at the memory clinic
      for mild memory complaints were included and underwent clinical and
      neuropsychological examination as well as standard brain imaging. A subset of
      patients was subjected to imaging biomarker studies as a part of routine clinical
      practice. RESULTS: Among the 1,190 patients evaluated during the study period,
      226 (19.0%) presented with mild memory complaints. Cerebrovascular disease was a
      common secondary cause. Nearly half of the patients (109 of 226) had MCI
      according to the modified Petersen criteria. All MCI subjects were educated and
      the majority were male. A total of 12% of the cohort was classified by imaging
      biomarkers as having MCI with intermediate likelihood of AD according to the NIA
      AA criteria. CONCLUSION: In the setting of urban India, MCI is an emerging
      problem; therefore, it was feasible to operationalise the revised NIA-AA criteria
      in identifying subjects with MCI with intermediate likelihood of AD.

PMID- 24135788
TI  - Nickel(I)-mediated transformations of carbon dioxide in closed synthetic cycles:
      reductive cleavage and coupling of CO2 generating Ni(I)CO, Ni(II)CO3 and
      Ni(II)C2O4Ni(II) entities.
AB  - The beta-diketiminato nickel(I) complex K2[L(tBu)Ni(I)(N2(2-))Ni(I)L(tBu)] reacts
      with CO2 via reductive disproportionation to form CO and CO3(2-) containing
      products, whereas after employment of the Ni(I) precursor
      [L(tBu)Ni(I)(N2)Ni(I)L(tBu)] reductive coupling of CO2 was observed giving an
      oxalate bridged dinickel(II) complex. The addition of KC8 to the carbonate and
      oxalate compounds formed leads to the regeneration of the initial Ni(I) complexes
      in an N2 atmosphere, thus closing synthetic cycles.

PMID- 24135786
TI  - Expression and epigenetic regulation of angiogenesis-related factors during
      dormancy and recurrent growth of ovarian carcinoma.
AB  - The initiation of angiogenesis can mark the transition from tumor dormancy to
      active growth and recurrence. Mechanisms that regulate recurrence in human
      cancers are poorly understood, in part because of the absence of relevant models.
      The induction of ARHI (DIRAS3) induces dormancy and autophagy in human ovarian
      cancer xenografts but produces autophagic cell death in culture. The addition of
      VEGF to cultures maintains the viability of dormant autophagic cancer cells,
      thereby permitting active growth when ARHI is downregulated, which mimics the
      "recurrence" of growth in xenografts. Two inducible ovarian cancer cell lines,
      SKOv3-ARHI and Hey-ARHI, were used. The expression level of angiogenesis factors
      was evaluated by real-time PCR, immunohistochemistry, immunocytochemistry and
      western blot; their epigenetic regulation was measured by bisulfite sequencing
      and chromatin immunoprecipitation. Six of the 15 angiogenesis factors were
      upregulated in dormant cancer cells (tissue inhibitor of metalloproteinases-3,
      TIMP3; thrombospondin-1, TSP1; angiopoietin-1; angiopoietin-2; angiopoietin-4; E
      cadherin, CDH1). We found that TIMP3 and CDH1 expression was regulated
      epigenetically and was related inversely to the DNA methylation of their
      promoters in cell cultures and in xenografts. Increased H3K9 acetylation was
      associated with higher TIMP3 expression in dormant SKOv3-ARHI cells, while
      decreased H3K27me3 resulted in the upregulation of TIMP3 in dormant Hey-ARHI
      cells. Elevated CDH1 expression during dormancy was associated with an increase
      in both H3K4me3 and H3K9Ac in two cell lines. CpG demethylating agents and/or
      histone deacetylase inhibitors inhibited the re-growth of dormant cancer cells,
      which was associated with the re-expression of anti-angiogenic genes. The
      expression of the anti-angiogenic genes TIMP3 and CDH1 is elevated during
      dormancy and is reduced during the transition to active growth by changes in DNA
      methylation and histone modification. 

PMID- 24135789
TI  - Light and acid dual-responsive organogel formation based on m-methyl red
      derivative.
AB  - A new gelator 1 that included m-methyl red was synthesized and fully
      characterized. It was found that the organogel of 1 was stable in DMSO even if
      the organogel was stimulated by acid or light. The organogel was thoroughly
      characterized using various microscopic techniques including field-emission
      scanning electron microscopy (FESEM), X-ray diffraction (XRD), UV-vis and Fourier
      transform infrared (FTIR) spectra. The organogel exhibited tunable structures and
      optical properties under different stimulation. The regular nanoring structure
      was turned into microspheres after the organogel in DMSO was stimulated at 254 nm
      light or acid. At the same time, the color of molecule 1 in gel state and
      solution state was all changed after stimulation by light or acid. The hydrogen
      bonding and pi-pi stacking were found to be the main driving forces for gel
      formation. This dual-responsive gel held promise for soft materials application
      in upscale smart responsive materials. 

PMID- 24135790
TI  - Circadian pathway genes in relation to glioma risk and outcome.
AB  - PURPOSE: There is growing evidence that circadian disruption may alter risk and
      aggressiveness of cancer. We evaluated common genetic variants in the circadian
      gene pathway for associations with glioma risk and patient outcome in a US clinic
      based case-control study. METHODS: Subjects were genotyped for 17 candidate
      single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2,
      PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to
      estimate age and gender-adjusted odds ratios (OR) and 95 % confidence intervals
      (CI) for glioma risk under three inheritance models (additive, dominant, and
      recessive). Proportional hazards regression was used to estimate hazard ratios
      for glioma-related death among 441 patients with high-grade tumors. Survival
      associations were validated using The Cancer Genome Atlas (TCGA) dataset.
      RESULTS: A variant in PER1 (rs2289591) was significantly associated with overall
      glioma risk (per variant allele OR 0.80; 95 % CI 0.66-0.97; p trend = 0.027). The
      variant allele for CLOCK rs11133391 under a recessive model increased risk of
      oligodendroglioma (OR 2.41; 95 % CI 1.31-4.42; p = 0.005), though not other
      glioma subtypes (p for heterogeneity = 0.0033). The association remained
      significant after false discovery rate adjustment (p = 0.008). Differential
      associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891
      though differences were not significant after adjustment for multiple testing. No
      consistent mortality associations were identified. Several of the examined genes
      exhibited differential expression in glioblastoma multiforme versus normal brain
      in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression
      of NPAS2 was significantly associated with a poor patient outcome in TCGA
      patients. CONCLUSION: This exploratory analysis provides some evidence supporting
      a role for circadian genes in the onset of glioma and possibly the outcome of
      glioma.

PMID- 24135791
TI  - Role of periplasmic binding proteins, FatB and VatD, in the vulnibactin
      utilization system of Vibrio vulnificus M2799.
AB  - Vibrio vulnificus, an opportunistic marine bacterium that causes a serious, often
      fatal, infection in humans, requires iron for its pathogenesis. This bacterium
      uses iron from the environment via the vulnibactin-mediated-iron-uptake system.
      In this study, we constructed the deletion mutants of the genes encoding the
      proteins involved in the vulnibactin-mediated-iron-uptake system, isochorismate
      synthase (ICS), vulnibactin utilization protein (VuuB), periplasmic ferric
      vulnibactin binding protein (FatB), and ferric-vulnibactin receptor protein
      (VuuA). The Deltaics and DeltavuuA mutants were unable to grow under low-iron
      concentration conditions compared with the isogenic wild-type, indicating that
      the involvement of ICS in the vulnibactin biosynthesis pathway and uptake of
      ferric-vulnibactin through the VuuA receptor protein are essential for V.
      vulnificus M2799 growth under low-iron concentration conditions. Similar growth
      impairment was also observed in DeltafatB, with growth recovery of this mutant
      observed 6 h after the beginning of the culture. These results indicate that
      there must be other periplasmic ferric-vulnibactin binding proteins in V.
      vulnificus M2799 that complement the defective fatB gene. Complementary growth
      studies confirmed that VatD protein, which functions as a periplasmic ferric
      aerobactin binding protein, was found to participate in the ferric-vulnibactin
      uptake system in the absence of FatB. Furthermore, the expression of ics, vuuB,
      fatB, vuuA, and vatD genes was found to be regulated by iron and the ferric
      uptake regulator. 

PMID- 24135792
TI  - A note on probabilistic models over strings: the linear algebra approach.
AB  - Probabilistic models over strings have played a key role in developing methods
      that take into consideration indels as phylogenetically informative events. There
      is an extensive literature on using automata and transducers on phylogenies to do
      inference on these probabilistic models, in which an important theoretical
      question is the complexity of computing the normalization of a class of string
      valued graphical models. This question has been investigated using tools from
      combinatorics, dynamic programming, and graph theory, and has practical
      applications in Bayesian phylogenetics. In this work, we revisit this theoretical
      question from a different point of view, based on linear algebra. The main
      contribution is a set of results based on this linear algebra view that
      facilitate the analysis and design of inference algorithms on string-valued
      graphical models. As an illustration, we use this method to give a new elementary
      proof of a known result on the complexity of inference on the "TKF91" model, a
      well-known probabilistic model over strings. Compared to previous work, our
      proving method is easier to extend to other models, since it relies on a novel
      weak condition, triangular transducers, which is easy to establish in practice.
      The linear algebra view provides a concise way of describing transducer
      algorithms and their compositions, opens the possibility of transferring fast
      linear algebra libraries (for example, based on GPUs), as well as low rank matrix
      approximation methods, to string-valued inference problems. 

PMID- 24135793
TI  - On the mechanical interplay between intra- and inter-synchronization during
      collective cell migration: a numerical investigation.
AB  - Collective cell migration is a fundamental process that takes place during
      several biological phenomena such as embryogenesis, immunity response, and
      tumorogenesis, but the mechanisms that regulate it are still unclear. Similarly
      to collective animal behavior, cells receive feedbacks in space and time, which
      control the direction of the migration and the synergy between the cells of the
      population, respectively. While in single cell migration intra-synchronization
      (i.e. the synchronization between the protrusion-contraction movement of the cell
      and the adhesion forces exerted by the cell to move forward) is a sufficient
      condition for an efficient migration, in collective cell migration the cells must
      communicate and coordinate their movement between each other in order to be as
      efficient as possible (i.e. inter-synchronization). Here, we propose a 2D
      mechanical model of a cell population, which is described as a continuum with
      embedded discrete cells with or without motility phenotype. The decomposition of
      the deformation gradient is employed to reproduce the cyclic active strains of
      each single cell (i.e. protrusion and contraction). We explore different modes of
      collective migration to investigate the mechanical interplay between intra- and
      inter-synchronization. The main objective of the paper is to evaluate the
      efficiency of the cell population in terms of covered distance and how the stress
      distribution inside the cohort and the single cells may in turn provide insights
      regarding such efficiency. 

PMID- 24135794
TI  - Multimodality and flexibility of stochastic gene expression.
AB  - We consider a general class of mathematical models for stochastic gene expression
      where the transcription rate is allowed to depend on a promoter state variable
      that can take an arbitrary (finite) number of values. We provide the solution of
      the master equations in the stationary limit, based on a factorization of the
      stochastic transition matrix that separates timescales and relative interaction
      strengths, and we express its entries in terms of parameters that have a natural
      physical and/or biological interpretation. The solution illustrates the capacity
      of multiple states promoters to generate multimodal distributions of gene
      products, without the need for feedback. Furthermore, using the example of a
      three states promoter operating at low, high, and intermediate expression levels,
      we show that using multiple states operons will typically lead to a significant
      reduction of noise in the system. The underlying mechanism is that a three-states
      promoter can change its level of expression from low to high by passing through
      an intermediate state with a much smaller increase of fluctuations than by means
      of a direct transition. 

PMID- 24135797
TI  - Optical coherence tomography imaging of erythroplasia of Queyrat and treatment
      with imiquimod 5% cream: a case report.
AB  - Lesion biopsy is currently used to diagnose erythroplasia of Queyrat (EQ), a rare
      squamous cell carcinoma in situ of the glans penis, or to determine whether the
      cancer is invasive, although the results only apply to the area from which the
      biopsy is taken. In this case report, we illustrate for the first time the use of
      optical coherence tomography (OCT) in imaging the entire lesion in a patient with
      EQ. The results confirmed that the patient had in situ rather than invasive
      carcinoma. Consequently, non-invasive treatment with imiquimod 5%, a topical
      immunomodulator with antitumour and antiviral properties, was initiated.
      Excellent clinical results were observed 4 weeks after the patient had been
      treated with imiquimod 5% three times a week for 8 weeks, which were confirmed
      using OCT imaging. One year later, there was still no evidence of pathology
      either clinically or via OCT imaging. OCT imaging should be used in conjunction
      with biopsy evaluation in the diagnostic work-up of EQ. Imiquimod 5% is a
      suitable treatment for patients with EQ, and the treatment response can be
      evaluated using OCT.

PMID- 24135795
TI  - From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent
      clinical, pathologic, and enteroendocrine characteristics.
AB  - GOALS: The aim of this report is to delineate the clinical, pathologic, and
      enteroendocrine (EE) features of prohormone convertase 1/3 (PC1/3) deficiency in
      children. BACKGROUND: Prohormone convertases play a pivotal role in the
      activation of biologically inactive hormones. Congenital defects in the EE axis,
      such as PC1/3 deficiency, have been rarely reported and their pathophysiological
      mechanisms are largely unknown. STUDY: EE function and pathology was evaluated in
      4 males (1, 2, 7, and 10 y old) from 2 families with PC1/3 deficiency at a
      university children's hospital. Clinical course, pathology analysis including
      immunohistochemistry for PC1/3, PC2, and glucagon-like peptide 1 (GLP-1) and
      electron microscopy, as well as EE function tests (GLP-1, GLP-2, oral glucose
      tolerance test) were performed. RESULTS: All (n=4) suffered from congenital
      severe diarrhea associated with malabsorption. The diarrhea improved during the
      first year of life and hyperphagia with excessive weight gain (BMI>97th
      percentile) became the predominant phenotype at an older age. Analysis of the
      enteroendocrine axis revealed high proinsulin levels (57 to 1116 pmol/L) in all
      patients, low serum GLP-2 levels, and impaired insulin and GLP-1 secretion after
      an oral glucose tolerance test at a young age, with improvement in 1 older child
      tested. Electron microscopy showed normal ultrastructure of enterocytes and EE
      cells. Immunohistochemistry revealed normal expression of chromogranin A, a
      marker of EE cells but markedly reduced immunostaining for PC1/3 and PC2 in all
      patients. CONCLUSIONS: PC1/3 deficiency is associated with an age dependent,
      variable clinical phenotype caused by severe abnormalities in intestinal and EE
      functions. Serum level of proinsulin can be used as an effective screening tool.

PMID- 24135798
TI  - An unusual cause of fetal hypomobility:congenital central hypoventilation
      syndrome associated with hirschsprung disease.
AB  - Co-occurrence of congenital central hypoventilation syndrome and Hirschsprung
      disease is known as Haddad syndrome. Affected patients develop with variable
      expressivity a dysfunction of the autonomic nervous system. We report the natural
      history of a full-term newborn infant presenting multiple features of autonomic
      system dysfunction that were already noted antenatally. The presence of a
      nonpolyalanine repeat expansion mutation in the PHOX2B gene confirmed postnatally
      the diagnosis of Haddad syndrome. This case suggests that patients presenting
      with autonomic system dysfunction may already present signs of the disease during
      the fetal period. Furthermore, antenatal presentations may correlate with a more
      severe presentation of the disease. In conclusion, antenatal signs of dysautonomy
      should stimulate multidisciplinary prenatal approach to orientate proper
      postnatal intervention and facilitate treatment strategies. 

PMID- 24135799
TI  - A rare cause of short stature: transsphenoidal encephalocele.
AB  - Basal encephaloceles are rare, accounting for about 1.5% of all encephaloceles.
      Transsphenoidal encephaloceles represent less than 5% of basal encephaloceles.
      Respiratory and feeding difficulties due to mass effect in the oral or nasal
      cavity and episodes of recurrent meningitis are the main clinical features.
      Diagnosis is established in the first year of life, but without characteristic
      facies, the diagnosis can be delayed to adolescence or adulthood. We report the
      case of a 10-year-old boy who presented with short stature and eventually was
      diagnosed with a growth hormone deficiency because of mass effect of
      transsphenoidal encephalocele. Unusual presentation of an encephalocele as a
      short stature is described.

PMID- 24135800
TI  - Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI
      applications.
AB  - As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures
      were extracted directly from the spin exchange optical pumping (SEOP) process
      through expansion followed by compression to ambient pressure for biomedical MRI
      applications. The omission of cryogenic gas separation generally requires the
      usage of high xenon or krypton concentrations at low SEOP gas pressures to
      generate hp (129)Xe or hp (83)Kr with sufficient MR signal intensity for imaging
      applications. Two different extraction schemes for the hp gasses were explored
      with focus on the preservation of the nuclear spin polarization. It was found
      that an extraction scheme based on an inflatable, pressure controlled balloon is
      sufficient for hp (129)Xe handling, while (83)Kr can efficiently be extracted
      through a single cycle piston pump. The extraction methods were tested for ex
      vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with
      oxygen, which may be of interest for potential in vivo applications, was
      accomplished during the extraction process using a piston pump. The (83)Kr bulk
      gas phase T1 relaxation in the mixtures containing more than approximately 1% O2
      was found to be slower than that of (129)Xe in corresponding mixtures. The
      experimental setup also facilitated (129)Xe T1 relaxation measurements as a
      function of O2 concentration within excised lungs. 

PMID- 24135801
TI  - Slice-selective gradient-encoded CEST spectroscopy for monitoring dynamic
      parameters and high-throughput sample characterization.
AB  - Chemical Exchange Saturation Transfer (CEST) NMR is an increasingly used
      technique for generating molecule or microenvironment specific signal contrast.
      To characterize CEST agents and to extract parameters such as temperature and pH,
      it is often required to resolve the spectral dimension. This is achieved by
      recording so called CEST- or z-spectra, where the spectral CEST information is
      conventionally acquired point by point, leading to long acquisition times. Here,
      we employ gradient-encoding to substantially accelerate the acquisition process
      of z-spectra in phantom experiments, reducing it to only two scans. This speedup
      allows us to monitor dynamic processes such as rapid temperature changes in a
      PARACEST sample that would be inaccessible with the conventional encoding.
      Furthermore, we combine the gradient-encoding approach with multi-slice
      selection, thus reserving one spatial dimension for the simultaneous
      investigation of heterogeneous PARACEST sample packages within one experiment.
      Hence, gradient-encoded CEST might be of great use for high-throughput screening
      of CEST contrast agents. 

PMID- 24135802
TI  - Outcomes of donor oocyte cycles in assisted reproduction.

PMID- 24135803
TI  - Effect of combined treatment with recombinant interleukin-2 and allicin on
      pancreatic cancer.
AB  - This study aimed to evaluate the efficacy of combined treatment with recombinant
      interleukin-2 (rIL-2) and allicin on pancreatic cancer and explore the potential
      immunological mechanism. A total of 60 C57/BL6 nude mice pancreatic cancer
      xenograft models were randomized into four groups of 15 mice per group: control
      group, allicin treatment group, rIL-2 treatment group, combined treatment with
      allicin and rIL-2 group. Mice in each group were treated with saline, rIL-2,
      allicin, or combination of rIL-2 and allicin by weekly i.v injection for four
      weeks. After four weeks of treatment, eyeballs of the mice were extracted and
      blood was drawn, percentages of CD4+T, CD8+T and NK cell were analyzed by FACS,
      IFN-gamma level was detected by ELISA. One mouse in each group was sacrificed to
      measure the weight and volume of the tumor and prepared to the paraffin section
      of tumor tissue. Apoptosis of the tumor cells was analyzed by TUNEL and FACS.
      Other mice continued to receive treatment, survival period were compared between
      each group. We observed a significant suppression of xenograft growth and a
      significant prolonged survival time in the combined treatment with allicin and
      rIL-2 group (P < 0.05). The most amount of apoptotic cells were observed in the
      combined therapy group (P < 0.05). The percentages of CD4+T, CD8+T and NK cell
      and serum IFN-gamma level increased significantly in the combined treatment group
      compared with other groups (P < 0.05). Combined treatment with allicin and rIL-2
      resulted in suppression of tumor growth and prolonged survival time possibly
      through activation of CD4+T, CD8+T and NK cell. 

PMID- 24135804
TI  - A phase 1/2 study of oral panobinostat combined with melphalan for patients with
      relapsed or refractory multiple myeloma.
AB  - Panobinostat is a histone deacetylase inhibitor that has shown synergistic
      preclinical anti-myeloma activity when combined with other agents, recently
      exhibiting synergy with the alkylating agent melphalan (Sanchez et al., Leuk Res
      35(3):373-379, 2011). This phase 1/2 trial investigated the safety and efficacy
      of panobinostat in combination with melphalan for relapsed/refractory multiple
      myeloma patients. There were four different trial treatment schedules due to
      tolerability issues, with the final treatment schedule (treatment schedule D)
      consisting of panobinostat (15 or 20 mg) and melphalan (0.05 or 0.10 mg/kg), both
      administered on days 1, 3, and 5 of a 28-day cycle. A total of 40 patients were
      enrolled; 3 in treatment schedule A, 9 in schedule B, 7 in schedule C, and
      finally 21 schedule D. Patients had been treated with a median of four regimens
      (range, 1-16) and two prior bortezomib-containing regimens (range, 0-9). Maximum
      tolerated dose was established at 20 mg panobinostat and 0.05 mg/kg melphalan in
      treatment schedule D. Overall, 3 patients (7.5 %) achieved >=partial response
      (two very good PRs and one PR) while 23 exhibited stable disease and 14 showed
      progressive disease. All three responders were enrolled in cohort 2 of treatment
      schedule B (panobinostat 20 mg thrice weekly continuously with melphalan 0.05
      mg/kg on days 1, 3, and 5). Neutropenia and thrombocytopenia were common, with
      30.8 and 23.1 % of patients exhibiting >=grade 3, respectively. Panobinostat +
      melphalan appears to have tolerability issues in a dosing regimen capable of
      producing a response. Care must be taken to balance tolerability and efficacy
      with this combination.

PMID- 24135805
TI  - MS/MS fragmentation behavior study of meso-phenylporphyrinoids containing
      nonpyrrolic heterocycles and meso-thienyl-substituted porphyrins.
AB  - Free base and cobalt(II) complexes of six meso-tetraphenylporphyrinoids
      containing nonpyrrolic heterocycles and of three meso-thienylporphyrins were
      investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS).
      Their fragmentation was studied in a quadrupole ion trap as a function of the
      porphyrinoid macrocycle structure and compared with the fragmentation behavior of
      the benchmark compound meso-tetraphenylporphyrin. In situ oxidation of the
      neutral cobalt(II) complexes under ESI conditions produced singly charged
      cobalt(III) porphyrinoid ions; the free bases were ionized by protonation. For
      the porphyrinoids with an intact porphyrin core, the major fragmentation pathways
      observed were the losses of the meso-substituent (for meso-phenyl groups) and
      characteristic fragmentations of one or more meso-substituents (for the meso
      thienyl group). Complex fragmentation pathways were observed for porphyrinoids
      with modifications to the porphyrin core but chemically reasonable structures
      could be assigned to most fragments, thus delineating general patterns for the
      behavior of pyrrole-modified porphyrins under CID conditions. ?

PMID- 24135806
TI  - Differentiation and distributions of DNA/cisplatin crosslinks by liquid
      chromatography-electrospray ionization-infrared multiphoton dissociation mass
      spectrometry.
AB  - Liquid chromatography-electrospray ionization-infrared multiphoton dissociation
      (IRMPD) mass spectrometry was developed to investigate the distributions of
      intrastrand crosslinks formed between cisplatin and two oligodeoxynucleotides
      (ODNs), d(A1T2G3G4G5T6A7C8C9C10A11T12) (G3-D) and its analog
      d(A1T2G3G4G5T6T7C8C9C10A11T12) (G3-H), which have been reported to adopt
      different secondary structures in solution. Based on the formation of site
      specific fragment ions upon IRMPD, two isobaric crosslink products were
      differentiated for each ODN. The preferential formation of G3G4 and G4G5
      crosslinks was determined as a function of reaction conditions, including
      incubation temperature and presence of metal ions. G3-D consistently exhibited a
      greater preference for formation of the G4G5 crosslink compared with the G3-H
      ODN. The ratio of G3G4:G4G5 crosslinks increased for both G3-D and G3-H at higher
      incubation temperatures or when metal salts were added. Comparison of the IRMPD
      fragmentation patterns of the unmodified ODNs and the intramolecular platinated
      crosslinks indicated that backbone cleavage was significantly suppressed near the
      crosslink. 

PMID- 24135807
TI  - Selective and nonselective cleavages in positive and negative CID of the
      fragments generated from in-source decay of intact proteins in MALDI-MS.
AB  - Selective and nonselective cleavages in ion trap low-energy collision-induced
      dissociation (CID) experiments of the fragments generated from in-source decay
      (ISD) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) of intact proteins are described in both positive and negative ion modes. The
      MALDI-ISD spectra of the proteins demonstrate common, discontinuous, abundant c-
      and z'-ions originating from cleavage at the N-Calpha bond of Xxx-Asp/Asn and Gly
      Xxx residues in both positive- and negative-ion modes. The positive ion CID of
      the c- and z'-ions resulted in product ions originating from selective cleavage
      at Asp-Xxx, Glu-Xxx and Cys-Xxx residues. Nonselective cleavage product ions
      rationalized by the mechanism of a "mobile proton" are also observed in positive
      ion CID spectra. Negative ion CID of the ISD fragments results in complex product
      ions accompanied by the loss of neutrals from b-, c-, and y-ions. The most
      characteristic feature of negative ion CID is selective cleavage of the peptide
      bonds of acidic residues, Xxx-Asp/Glu/Cys. A definite influence of alpha-helix on
      the CID product ions was not obtained. However, the results from positive ion and
      negative ion CID of the MALDI-ISD fragments that may have long alpha-helical
      domains suggest that acidic residues in helix-free regions tend to degrade more
      than those in helical regions. 

PMID- 24135808
TI  - Nucleophilic aromatic substitution with dianions: reactions driven by the release
      of Coulomb repulsion.
AB  - The reactions of a nucleophilic dianion with a series of activated aryl bromides
      were studied in the gas phase. Nucleophilic aromatic substitution (SNAr) as well
      as proton transfer reactions were observed. Rate constants and branching ratios
      were determined for all the reactions and the experimental data are supported by
      ab initio calculations. Reactions with bis-trifluoromethylbromobenzenes give only
      SNAr reactions and the rate constants follow the expected pattern, with
      substituents at the ortho and para positions having the greatest impact.
      Reactions of polyfluorobromobenzenes give a mix of proton transfer (when
      possible) and SNAr, with both bromide and fluoride acting as leaving groups. The
      latter is much less thermodynamically favorable but is the dominant pathway in
      each case. The selectivity of the reactions indicate that the products are
      determined early on the potential energy surface, before there is significant
      cleavage of the bond to the leaving group-the reaction is potentially directed by
      the initial formation of a hydrogen bond with the arene. The computational data
      also suggest that hydrogen bonding in the product ion-ion complexes can stabilize
      the system until there is sufficient charge separation to use the internal
      Coulomb repulsion to drive the reactions to products. Overall, the results
      highlight (1) the ability of multiply-charged systems to efficiently funnel their
      Coulomb repulsion into reaction processes that are intrinsically unfavorable, and
      (2) the high degree of selectivity that can be attained even in systems with
      multiple, low-barrier pathways. 

PMID- 24135809
TI  - Pre-stroke CHADS2 and CHA2DS2-VASc scores are useful in stratifying three-month
      outcomes in patients with and without atrial fibrillation.
AB  - BACKGROUND: CHADS2 and CHA2DS2-VASc scores are validated tools for assessing
      stroke risk in patients with atrial fibrillation (AF). We investigated whether
      these scores are associated with 3-month stroke outcomes and evaluated the
      utility of these scores in stratifying 3-month stroke outcomes in both patients
      with and without AF. METHODS: We analysed 6,612 acute ischaemic stroke patients
      from the Virtual International Stroke Trials Archive who received either placebo
      or ineffective active treatments not associated with significant cardiac
      complications. Outcomes included 3-month mortality, good functional outcomes
      defined as modified Rankin Scale score <=1 and serious cardiac adverse events
      (SCAEs) defined as one of acute coronary syndrome, symptomatic heart failure,
      cardiopulmonary arrest, life-threatening arrhythmia and cardiac death. The
      association between the pre-stroke CHADS2 and CHA2DS2-VASc scores and 3-month
      stroke outcomes was assessed using binary logistic regression. The utility of the
      two scores in estimating 3-month stroke outcomes was assessed using area under
      the receiver operator characteristic curves (AUC) and compared using the chi(2)
      test. RESULTS: In this cohort, 26.5% had AF, 35.3% received IV tissue plasminogen
      activator (tPA), 17.7% died, 25.1% achieved good functional outcomes and 9.5% had
      >=1 SCAE at 3 months. High-risk (>=2) pre-stroke CHADS2 and CHA2DS2-VASc scores
      are both associated with 3-month mortality (CHADS2: odds ratio, OR, 2.33, 95%
      confidence interval 1.81-3.00; CHA2DS2-VASc: OR 3.01, 2.00-4.80), good functional
      outcomes (CHADS2: OR 0.47, 0.39-0.57; CHA2DS2-VASc: OR 0.55, 0.42-0.71) and SCAEs
      (CHADS2: OR 1.76, 1.28-2.42; CHA2DS2-VASc: OR 2.69, 1.53-4.73) after adjusting
      for baseline differences in neurological impairment, tPA use and AF. The pre
      stroke CHA2DS2-VASc score is better than the CHADS2 score in estimating 3-month
      stroke outcomes in both patients with and without AF (p <= 0.005 in all AUC
      comparisons). High-risk pre-stroke CHA2DS2-VASc score has high sensitivity for
      mortality (AF: 0.96, 0.94-0.98; no AF: 0.88, 0.86-0.91) and negative predictive
      value for SCAE (AF: 0.93, 0.87-0.96; no AF: 0.96, 0.95-0.97) within 3 months. Low
      risk pre-stroke CHA2DS2-VASc score has high specificity for good functional
      outcome (AF: 0.99, 0.98-0.994; no AF: 0.94, 0.93-0.95) at 3 months. CONCLUSIONS:
      The pre-stroke CHA2DS2-VASc score appears to be a simple tool for identifying
      patients at lower risk of poor outcomes and serious cardiac complications within
      3 months following ischaemic stroke in patients with and without AF. (c) 2013 S.
      Karger AG, Basel.

PMID- 24135810
TI  - Experimental and modeling study of the oxidation of n-butane in a jet stirred
      reactor using cw-CRDS measurements.
AB  - The gas-phase oxidation of n-butane has been studied in an atmospheric jet
      stirred reactor (JSR) at temperatures up to 950 K. For the first time, continuous
      wave cavity ring-down spectroscopy (cw-CRDS) in the near-infrared has been used,
      together with gas chromatography (GC), to analyze the products formed during its
      oxidation. In addition to the quantification of formaldehyde and water, which is
      always difficult by GC, cw-CRDS allowed as well the quantification of hydrogen
      peroxide (H2O2). A comparison of the obtained mole fraction temperature profiles
      with simulations using a detailed gas-phase mechanism shows a good agreement at
      temperatures below 750 K, but an overestimation of the overall reactivity above
      this temperature. Also, a strong overestimation was found for the H2O2 mole
      fraction at higher temperatures. In order to improve the agreement between model
      and experimental results, two modifications have been implemented to the model:
      (a) the rate constant for the decomposition of H2O2 (+M) <-> 2OH (+M) has been
      updated to the value recently proposed by Troe (Combust. Flame, 2011, 158, 594
      601) and (b) a temperature dependent heterogeneous destruction of H2O2 on the hot
      reactor walls with assumed rate parameters has been added. The improvement (a)
      slows down the overall reactivity at higher temperatures, but has a negligible
      impact on the maximal H2O2 mole fraction. Improvement (b) has also a small impact
      on the overall reactivity at higher temperatures, but a large effect on the
      maximal H2O2 mole fraction. Both modifications lead to an improved agreement
      between model and experiment for the oxidation of n-butane in a JSR at
      temperatures above 750 K. 

PMID- 24135811
TI  - The long road to acceptance. Commentary on O. Chowdhury et al.: Randomised trial
      of volume-targeted ventilation versus pressure-limited ventilation in acute
      respiratory failure in prematurely born infants (Neonatology 2013;104:290-294).

PMID- 24135812
TI  - Tattooing: a reminder of bygone follies.

PMID- 24135813
TI  - Self-healing of the superhydrophobicity by ironing for the abrasion durable
      superhydrophobic cotton fabrics.
AB  - Self-healing of the superhydrophobic cotton fabric (SCF) obtained by the
      radiation-induced graft polymerization of lauryl methacrylate (LMA) and n-hexyl
      methacrylate (HMA), can be achieved by ironing. Through the steam ironing
      process, the superhydrophobicity of the SCFs will be regenerated even after the
      yarns are ruptured during the abrasion test under a load pressure of 44.8 kPa.
      SCFs made from LMA grafted cotton fabric can ultimately withstand at least 24,000
      cycles of abrasion with periodic steam ironing. The FT-IR microscope results show
      that the migration of the polymethacrylates graft chains from the interior to the
      surface is responsible for the self-healing effect. 

PMID- 24135814
TI  - Persistent orchialgia after inguinal hernia repair: diagnosis, neuroanatomy, and
      surgical management: Invited comment to: Role of orchiectomy in severe testicular
      pain and inguinal hernia surgery: audit of Finnish patient insurance centre.
      Ronka K, Vironen J, Kokki H, Liukkonen T, Paajanen H. DOI 10.1007/s10029-013-1150
      3.

PMID- 24135815
TI  - Managing competing demands through task-switching and multitasking: a multi
      setting observational study of 200 clinicians over 1000 hours.
AB  - OBJECTIVE: To provide a detailed characterisation of clinicians' work management
      strategies. DESIGN: 1002.3 h of observational data were derived from three
      previous studies conducted in a teaching hospital in Sydney, Australia, among
      emergency department (ED) doctors (n=40), ward doctors (n=57) and ward nurses
      (n=104). The rates of task-switching (pausing a task to handle an incoming task)
      and multitasking (adding a task in parallel to an existing task) were compared in
      each group. Random intercepts logistic regression was used to determine factors
      significantly associated with clinicians' use of task-switching over multitasking
      and to quantify variation between individual clinicians. RESULTS: Task-switching
      rates were higher among ED doctors (6.0 per hour) than ward staff (2.2 and 1.8
      per hour for doctors and nurses, respectively) and vice versa for multitasking
      rates (9.2 vs 17.3 and 14.1 per hour). Clinicians' strategy use was significantly
      related to the nature and complexity of work and to the person they were working
      with. In some settings, time of day, day of the week or previous chosen strategy
      affected a clinician's strategy. Independent of these factors, there was
      significant variation between individual clinicians in their use of strategies in
      a given situation (ED doctors p=0.04, ward staff p=0.03). CONCLUSIONS: Despite
      differences in factors associated with work management strategy use among ED
      doctors, ward doctors and ward nurses, clinicians in all settings appeared to
      prioritise certain types of tasks over others. Documentation was generally given
      low priority in all groups, while the arrival of direct care tasks tended to be
      treated with high priority. These findings suggest that considerations of safety
      may be implicit in task-switching and multitasking decisions. Although these
      strategies have been cast in a negative light, future research should consider
      their role in optimising competing quality and efficiency demands.

PMID- 24135817
TI  - Stent implantation in patients with metal allergy: a systemic review and meta
      analysis.
AB  - OBJECTIVES: The aim of this study was to assess whether outcomes of patients with
      metal allergy after coronary stent implantation differ from those of patients
      without metal allergy. METHODS: A meta-analysis was carried out to compare the
      outcome in patients who are allergic to the metal material of a stent with those
      who are nonallergic. A computer-based online retrieval of databases and manual
      searches were performed to identify articles that addressed the association
      between in-stent restenosis (ISR) and contact allergy to stent materials, without
      language restrictions. The meta-analysis was carried out with a fixed-effect
      model using STATA 11. Odds ratio (OR) was used as an effect size. RESULT: Nine
      relevant articles, encompassing 1223 patients, were identified. Being allergic to
      stent material obviously increased the risk of ISR. With the fixed model, ORs for
      allergic patients and nonallergic patients were 2.65 (confidence interval 1.82
      3.82). A subgroup analysis of race was carried out. OR in the Asian group was
      higher than that in the European group (3.71 vs. 2.25), which might suggest that
      Asians who are allergic to stent material have a higher risk of ISR than
      Europeans. CONCLUSION: Allergy to stent material worsens the prognosis of
      patients with coronary stent implantation. New well-designed prospective clinical
      trials are required to confirm this relationship and to establish the
      indispensability of a skin patch test before coronary stent implantation.

PMID- 24135816
TI  - Fibroblast growth factor receptor 1 as a putative therapy target in colorectal
      cancer.
AB  - BACKGROUND/AIMS: Resembling a potential therapeutic drug target, fibroblast
      growth factor receptor 1 (FGFR1) amplification and expression was assessed in 515
      human colorectal cancer (CRC) tissue samples, lymph node metastases and CRC cell
      lines. METHODS: FGFR1 amplification status was determined using fluorescence in
      situ hybridization. Additionally, we assessed protein levels employing Western
      blots and immunohistochemistry. The FGFR1 mRNA localization was analyzed using
      mRNA in situ hybridization. Functional studies employed the FGFR inhibitor NVP
      BGJ398. RESULTS: Of 454 primary CRCs, 24 displayed FGFR1 amplification. 92/94
      lymph node metastases presented the same amplification status as the primary
      tumor. Of 99 investigated tumors, 18 revealed membranous activated pFGFR1
      protein. FGFR1 mRNA levels were independent of the amplification status or pFGFR1
      protein occurrence. In vitro, a strong antiproliferative effect of NVP-BGJ398
      could be detected in cell lines exhibiting high FGFR1 protein. CONCLUSION: FGFR1
      is a potential therapeutic target in a subset of CRC. FGFR1 protein is likely to
      represent a central factor limiting the efficacy of FGFR inhibitors. The lack of
      correlation between its evaluation at genetic/mRNA level and its protein
      occurrence indicates that the assessment of the receptor at an
      immunohistochemical level most likely represents a suitable way to assess FGFR1
      as a predictive biomarker for patient selection in future clinical trials.

PMID- 24135818
TI  - Characterization of a bioflocculant produced by a consortium of Halomonas sp.
      Okoh and Micrococcus sp. Leo.
AB  - The physicochemical and flocculating properties of a bioflocculant produced by a
      bacterial consortium composed of Halomonas sp. Okoh and Micrococcus sp. Leo were
      investigated. The purified bioflocculant was cation and pH dependent, and
      optimally flocculated kaolin clay suspension at a dosage of 0.1 mg/mL. The
      flocculating activity of the bioflocculant was stimulated in the presence of
      Ca2+, Mn2+, Al3+ and had a wide pH range of 2-10, with the highest flocculating
      activity of 86% at pH 8. The bioflocculant was thermostable and retained more
      than 70% of its flocculating activity after being heated at 80  degrees C for 30
      min. Thermogravimetric analyses revealed a partial thermal decomposition of the
      biofloculant at 400  degrees C. The infrared spectrum showed the presence of
      hydroxyl, carboxyl and amino moieties as functional groups. The bioflocculant
      produced by the bacterial consortium appears to hold promising alternative to
      inorganic and synthetic organic flocculants that are widely used in wastewater
      treatment. 

PMID- 24135820
TI  - The measurement of dry deposition and surface runoff to quantify urban road
      pollution in Taipei, Taiwan.
AB  - Pollutants deposited on road surfaces and distributed in the environment are a
      source of nonpoint pollution. Field data are traditionally hard to collect from
      roads because of constant traffic. In this study, in cooperation with the traffic
      administration, the dry deposition on and road runoff from urban roads was
      measured in Taipei City and New Taipei City, Taiwan. The results showed that the
      dry deposition is 2.01-5.14 g/m(2) . day and 78-87% of these solids are in the 75
      300 um size range. The heavy metals in the dry deposited particles are mainly Fe,
      Zn, and Na, with average concentrations of 34,978, 1,519 and 1,502 ppm,
      respectively. Elevated express roads show the highest heavy metal concentrations.
      Not only the number of vehicles, but also the speed of the traffic should be
      considered as factors that influence road pollution, as high speeds may
      accelerate vehicle wear and deposit more heavy metals on road surfaces. In
      addition to dry deposition, the runoff and water quality was analyzed every five
      minutes during the first two hours of storm events to capture the properties of
      the first flush road runoff. The sample mean concentration (SMC) from three roads
      demonstrated that the first flush runoff had a high pollution content, notably
      for suspended solid (SS), chemical oxygen demand (COD), oil and grease, Pb, and
      Zn. Regular sweeping and onsite water treatment facilities are suggested to
      minimize the pollution from urban roads.

PMID- 24135819
TI  - Molecular epidemiology and evolution of West Nile virus in North America.
AB  - West Nile virus (WNV) was introduced to New York in 1999 and rapidly spread
      throughout North America and into parts of Central and South America.
      Displacement of the original New York (NY99) genotype by the North America/West
      Nile 2002 (NA/WN02) genotype occurred in 2002 with subsequent identification of a
      novel genotype in 2003 in isolates collected from the southwestern Unites States
      region (SW/WN03 genotype). Both genotypes co-circulate to date. Subsequent WNV
      surveillance studies have confirmed additional genotypes in the United States
      that have become extinct due to lack of a selective advantage or stochastic
      effect; however, the dynamic emergence, displacement, and extinction of multiple
      WNV genotypes in the US from 1999-2012 indicates the continued evolution of WNV
      in North America. 

PMID- 24135821
TI  - Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette
      vapour extract on cultured myocardial cells.
AB  - BACKGROUND: Electronic cigarettes (ECs) have been marketed as an alternative-to
      smoking habit. Besides chemical studies of the content of EC liquids or vapour,
      little research has been conducted on their in vitro effects. Smoking is an
      important risk factor for cardiovascular disease and cigarette smoke (CS) has
      well-established cytotoxic effects on myocardial cells. The purpose of this study
      was to evaluate the cytotoxic potential of the vapour of 20 EC liquid samples and
      a "base" liquid sample (50% glycerol and 50% propylene glycol, with no nicotine
      or flavourings) on cultured myocardial cells. Included were 4 samples produced by
      using cured tobacco leaves in order to extract the tobacco flavour. METHODS:
      Cytotoxicity was tested according to the ISO 10993-5 standard. By activating an
      EC device at 3.7 volts (6.2 watts-all samples, including the "base" liquid) and
      at 4.5 volts (9.2 watts-four randomly selected samples), 200 mg of liquid
      evaporated and was extracted in 20 mL of culture medium. Cigarette smoke (CS)
      extract from three tobacco cigarettes was produced according to ISO 3308 method
      (2 s puffs of 35 mL volume, one puff every 60 s). The extracts, undiluted (100%)
      and in four dilutions (50%, 25%, 12.5%, and 6.25%), were applied to myocardial
      cells (H9c2); percent-viability was measured after 24 h incubation. According to
      ISO 10993-5, viability of <70% was considered cytotoxic. RESULTS: CS extract was
      cytotoxic at extract concentrations >6.25% (viability: 76.9 +/- 2.0% at 6.25%,
      38.2 +/- 0.5% at 12.5%, 3.1 +/- 0.2% at 25%, 5.2 +/- 0.8% at 50%, and 3.9 +/-
      0.2% at 100% extract concentration). Three EC extracts (produced by tobacco
      leaves) were cytotoxic at 100% and 50% extract concentrations (viability range:
      2.2%-39.1% and 7.4%-66.9% respectively) and one ("Cinnamon-Cookies" flavour) was
      cytotoxic at 100% concentration only (viability: 64.8 +/- 2.5%). Inhibitory
      concentration 50 was >3 times lower in CS extract compared to the worst
      performing EC vapour extract. For EC extracts produced by high-voltage and
      energy, viability was reduced but no sample was cytotoxic according to ISO 10993
      5 definition. Vapour produced by the "base" liquid was not cytotoxic at any
      extract concentration. Cell survival was not associated with nicotine
      concentration of EC liquids. CONCLUSIONS: This study indicates that some EC
      samples have cytotoxic properties on cultured cardiomyoblasts, associated with
      the production process and materials used in flavourings. However, all EC vapour
      extracts were significantly less cytotoxic compared to CS extract.

PMID- 24135823
TI  - [Rare tumor of the nasal cavity hidden in a nasal polyposis].

PMID- 24135822
TI  - Study on association between spatial distribution of metal mines and disease
      mortality: a case study in Suxian District, South China.
AB  - Metal mines release toxic substances into the environment and can therefore
      negatively impact the health of residents in nearby regions. This paper sought to
      investigate whether there was excess disease mortality in populations in the
      vicinity of the mining area in Suxian District, South China. The spatial
      distribution of metal mining and related activities from 1985 to 2012, which was
      derived from remote sensing imagery, was overlapped with disease mortality data.
      Three hotspot areas with high disease mortality were identified around the
      Shizhuyuan mine sites, i.e., the Dengjiatang metal smelting sites, and the
      Xianxichong mine sites. Disease mortality decreased with the distance to the
      mining and smelting areas. Population exposure to pollution was estimated on the
      basis of distance from town of residence to pollution source. The risk of dying
      according to disease mortality rates was analyzed within 7-25 km buffers. The
      results suggested that there was a close relationship between the risk of disease
      mortality and proximity to the Suxian District mining industries. These
      associations were dependent on the type and scale of mining activities, the area
      influenced by mining and so on. 

PMID- 24135824
TI  - [Epistaxis and anticoagulation - a medical and economic challenge?].
AB  - BACKGROUND: According to recent statistics more and more elderly patients are
      hospitalized due to epistaxis and need anticoagulation. Aim of the present study
      was to investigate if it was more complex to treat anticoagulated patients than
      non-anticoagulated patients, if these patients needed a longer hospital stay and
      to characterize the study population in terms of the various applied therapeutic
      methods. METHODS: Retrospective study, collecting clinical data of all in
      patients treated between 1.1.2007 to 1.8.2011 at an ENT-Department of an
      University Clinic due to epistaxis. RESULTS: Of 656 patients 265 were not
      anticoagulated, 391 were anticoagulated. The mean patients' age increased
      statistically significant. Patients without anticoagulation were significantly
      younger than patients with anticoagulation. The duration of the hospitalization
      differed significantly between the groups, with the longest for patients treated
      with warfarin (5.4 days). 71 patients underwent surgical treatment of epistaxis
      (cautery of the sphenopalatine artery or anterior ethmoid artery). CONCLUSION:
      During the study period an increasing number of more elderly patients needed
      hospitalization due to epistaxis. The duration of hospitalization differed
      significantly between the groups, with longer stays for the anticoagulated
      patients. Currently, treatment of epistaxis patients however is reimbursed
      independently of the presence of comorbidities or anticoagulation therapy. For
      the further development of the German DRG System a new split of the epistaxis DRG
      should be considered.

PMID- 24135825
TI  - [NiTiBOND an optimized self-crimping stapes prosthesis for treatment of
      otosclerosis].
AB  - BACKGROUND: Compared to traditional stapes prostheses, self-crimping prostheses
      have been shown to result in similar, if not better, closure of the air bone gap
      in patients undergoing stapedotomy for otosclerosis. To achieve self-crimping,
      nitinol, a shape memory alloy, has been used for several years but concerns have
      been raised regarding possible damage to the incus and its muco-periosteum. We
      investigate these concerns with regard to the newer NiTiBOND stapes prosthesis in
      an observational multi-centre study. MATERIAL AND METHODS: In a multicentre,
      prospective observational study, 76 patients undergoing stapedotomy with the
      NiTiBond prosthesis across 4 centres were compared to 75 -retrospectively
      selected control SMart patients. Complications, intra-operative user-friendliness
      and audiological results at 3 months were documented. RESULTS: Audiological
      improvement and the rate of complications were similar in both groups. Non
      inferiority was shown at all frequencies and in the pure-tone average. The
      NiTiBOND prosthesis was described as very user-friendly. CONCLUSIONS: By
      eliminating manual crimping, stapedotomy using the NiTiBOND prosthesis can be
      facilitated and standardized. Furthermore, intraoperative handling
      characteristics of the prosthesis are very good which may further reduce
      operative risk. Importantly, we show that these benefits are not to the detriment
      of audiological outcome. Larger and longer-term studies are required to further
      evaluate results.

PMID- 24135826
TI  - [Etiology, diagnosis, differential diagnosis and therapy of vocal fold
      paralysis].
AB  - Etiology of vocal fold paralysis is broad: e. g. iatrogenic/traumatic, associated
      with neoplasms or with systemic diseases. The cause of idiopathic paralysis is
      unknown. The main symptom of unilateral vocal fold paralysis is hoarseness
      because of a remaining glottic gap during phonation. Patients with bilateral
      vocal fold paralysis typically have no impairment of the voice but dyspnea.
      Examination of patients with an idopathic vocal fold paralysis is a CT of the
      vagal nerve and recurrent laryngeal nerve from skull base to neck and
      mediastinum. Serological tests are not obligatory. Differential diagnosis of
      vocal fold immobility is vocal fold paralysis/neurological causes and arthrogene
      causes such as arytenoid subluxation, interarytenoid adhesion and vocal fold
      fixation in laryngeal carcinomas. Voice therapy is a promising approach for
      patients with unilateral vocal fold paralysis, but not all patients benefit
      sufficiently. Temporary vocal fold augmentation by injection medialization
      results in satisfactory voice quality that is comparable with a thyroplasty.
      Patients with bilateral vocal fold immobility show typically dyspnea requiring
      immediate therapy such as temporary tracheotomy or reversible laterofixation of
      the paralyzed vocal chord. If the paralysis persists a definitive enlargement of
      the glottic airway by eg. arytenoidectomy needs to be performed. 

PMID- 24135827
TI  - Incorporation by coordination and release of the iron chelator drug deferiprone
      from zinc-based metal-organic frameworks.
AB  - A series of new zinc-based metal-organic framework materials has been prepared in
      which deferiprone is incorporated as a chelating ligand on infinite or tri-zinc
      secondary building units following deprotonation. Deferiprone is immediately
      released from the MOFs on treatments with 1 N hydrochloric acid or buffer, but
      slow release is observed in ethanoic acid. 

PMID- 24135828
TI  - Rapid detection of MYD88-L265P mutation by PCR-RFLP in B-cell lymphoproliferative
      disorders.

PMID- 24135829
TI  - A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of
      diffuse large B-cell lymphoma.
AB  - Dysregulated expression of factors that control protein synthesis is associated
      with poor prognosis of many cancers, but the underlying mechanisms are not well
      defined. Analysis of the diffuse large B-cell lymphoma (DLBCL) translatome
      revealed selective upregulation of mRNAs encoding anti-apoptotic and DNA repair
      proteins. We show that enhanced synthesis of these proteins in DLBCL is mediated
      by the relief of repression that is normally imposed by structure in the 5'
      untranslated regions of their corresponding mRNAs. This process is driven by
      signaling through mammalian target of rapamycin, resulting in increased synthesis
      of eukaryotic initiation factor (eIF) 4B complex (eIF4B), a known activator of
      the RNA helicase eIF4A. Reducing eIF4B expression alone is sufficient to decrease
      synthesis of proteins associated with enhanced tumor cell survival, namely DAXX,
      BCL2 and ERCC5. Importantly, eIF4B-driven expression of these key survival
      proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5
      are identified as novel prognostic markers for poor survival in DLBCL. Our work
      provides new insights into the mechanisms by which the cancer-promoting
      translational machinery drives lymphomagenesis. 

PMID- 24135830
TI  - Synergetic inactivation of Staphylococcus epidermidis and Streptococcus mutansin
      a TiO2/H2O2/UV system.
AB  - TiO 2 photocatalysis can be used to kill surface adherent bacteria on
      biomaterials, and is particularly interesting for use with percutaneous implants
      and devices. Its efficiency and safety, however, depend on the activation energy
      required. This in vitro study investigates synergetic effects against the
      clinically relevant strains S. epidermidis and S. mutans when combining
      photocatalytic surfaces with H2O2. After 20 min exposure to 0.1 wt% H2O2 and UV
      light on TiO2 surfaces, viabilities of S. epidermidis and S. mutans were reduced
      by 99.7% and 98.9%, respectively. Without H2O2 the corresponding viability
      reduction was 86% for S. epidermidis and 65% for S. mutans. This study indicates
      that low concentrations of H2O2 can enhance the efficiency of photocatalytic TiO2
      surfaces, which could potentially improve current techniques used for
      decontamination and debridement of TiO2 coated biomedical implants and devices.

PMID- 24135831
TI  - Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B
      type natriuretic peptide levels compared with beta-blockers in patients with
      permanent atrial fibrillation.
AB  - AIMS: Rate control of atrial fibrillation (AF) has become a main treatment
      modality, but we need more knowledge regarding the different drugs used for this
      purpose. In this study, we aimed to compare the effect of four common rate
      reducing drugs on exercise capacity and levels of N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) in patients with permanent AF. METHODS AND
      RESULTS: We included 60 patients (mean age 71 +/- 9 years, 18 women) with
      permanent AF and normal left ventricular function in a randomized, cross-over,
      investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg,
      and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the
      last day of each treatment period, the patients underwent a maximal
      cardiopulmonary exercise test and blood samples were obtained at rest and at peak
      exercise. The exercise capacity (peak VO2) was significantly lower during
      treatment with metoprolol and carvedilol compared with baseline (no treatment) or
      treatment with diltiazem and verapamil (P < 0.001 for all). Compared with
      baseline, treatment with diltiazem and verapamil significantly reduced the NT
      proBNP levels both at rest and at peak exercise, whereas treatment with
      metoprolol and carvedilol increased the levels (P < 0.05 for all). CONCLUSION:
      Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity
      and reduced levels of NT-proBNP compared with baseline, whereas treatment with
      metoprolol or carvedilol reduced the exercise capacity and increased levels of NT
      proBNP.

PMID- 24135833
TI  - Newly diagnosed aortic arch interruption in an adult presenting with heart
      failure.

PMID- 24135834
TI  - Ventricular tachycardia in hypertrophic cardiomyopathy with apical aneurysm
      successfully treated with left ventricular aneurysmectomy and cryoablation.

PMID- 24135832
TI  - Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial
      fibrillation: a multicentre, randomized, controlled trial (SARA study).
AB  - BACKGROUND: Catheter ablation (CA) is a highly effective therapy for the
      treatment of paroxysmal atrial fibrillation (AF) when compared with
      antiarrhythmic drug therapy (ADT). No randomized studies have compared the two
      strategies in persistent AF. The present randomized trial aimed to compare the
      effectiveness of CA vs. ADT in treating persistent AF. METHODS AND RESULTS:
      Patients with persistent AF were randomly assigned to CA or ADT (excluding
      patients with long-standing persistent AF). Primary endpoint at 12-month follow
      up was defined as any episode of AF or atrial flutter lasting >24 h that occurred
      after a 3-month blanking period. Secondary endpoints were any atrial
      tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In
      total, 146 patients were included (aged 55 +/- 9 years, 77% male). The ADT group
      received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat
      analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%)
      in the ADT group were free of the primary endpoint (P = 0.002), implying an
      absolute risk difference of 26.6% (95% CI 10.0-43.3) in favour of CA. The
      proportion of patients free of any recurrence (>30 s) was higher in the CA group
      than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less
      frequent (34.7 vs. 50%, respectively; P = 0.018). CONCLUSION: Catheter ablation
      is superior to medical therapy for the maintenance of sinus rhythm in patients
      with persistent AF at 12-month follow-up. CLINICAL TRIAL REGISTRATION
      INFORMATION: NCT00863213 (http://clinicaltrials.gov/ct2/show/NCT00863213).

PMID- 24135835
TI  - Early change in invasive measures of microvascular function can predict
      myocardial recovery following PCI for ST-elevation myocardial infarction.
AB  - AIMS: Predicting the likely success of primary PCI to salvage potential infarcted
      myocardium is desirable. We compared early invasive parameters of coronary
      microcirculation function with the levels of circulating endothelin (ET-1) and 6
      month ejection fraction after STEMI. METHODS AND RESULTS: Forty-four STEMI
      patients underwent assessment of coronary flow reserve (CFR) and index of
      myocardial resistance (IMR) on completion of PPCI and one day later. Cardiac
      magnetic resonance (CMR) at 24 h and 6 months assessed ejection fraction, oedema,
      late gadolinium enhancement, and salvage. In patients with depressed EF, there
      was no difference in IMR or CFR measured immediately after PPCI compared with
      those with preserved EF. However, by Day 1, CFR was significantly lower in those
      with depressed EF [2.0(1.5-2.3) vs. 2.6(2.1-3.3), P = 0.008]. In multivariable
      models, higher CFR post-PPCI [EST: +8.9 (SE 3.7) per 1 CFR unit, P = 0.03] and
      greater increase in CFR between post-PPCI and Day 1 [EST: +8.5 (SE 3.4) per 1 CFR
      unit, P = 0.01] were associated with higher salvage index. Circulating endothelin
      levels were significantly elevated in the low EF group at both 6 and 24 h, and 24
      h levels correlated with CFR. CONCLUSION: Changes of the coronary
      microcirculation in the first day after PPCI are associated with 6-month ejection
      fraction and myocardial salvage. Depressed CFR at 24 h is associated with CMR
      imaging indices of MVO and haemorrhage and elevated endothelin levels.

PMID- 24135836
TI  - A rare case of multi-chambered fungal endocarditis from a virulent Cunninghamella
      infection.

PMID- 24135837
TI  - Assessment of the vortex flow in the post-stenotic dilatation above the pulmonary
      valve stenosis in an infant using echocardiography vector flow mapping.

PMID- 24135838
TI  - Response to 'Reduced diurnal variation of heart rate is associated with increased
      plasma B-type natriuretic peptide level in patients with atrial fibrillation'.

PMID- 24135839
TI  - Longitudinal effects of selective serotonin reuptake inhibitor therapy and
      cytokine-related depression on hepatitis C viral logs during antiviral therapy.
AB  - OBJECTIVES: The aim of this study was to determine the longitudinal effects of
      selective serotonin reuptake inhibitor (SSRI) therapy and cytokine-related
      depression on levels of hepatitis C virus (HCV) during treatment with combination
      therapy. BACKGROUND: Prior studies have investigated the association between
      cytokine-related depression and sustained virological response, but it is unknown
      whether anti-inflammatory properties of SSRIs used to treat cytokine-related
      depression inadvertently contravene proinflammatory properties of pegylated
      interferon (Peg-IFN), in effect reducing therapeutic efficacy. STUDY: In a
      retrospective cohort design, patients being treated with Peg-IFN or interferon in
      combination with ribavirin at a gastroenterology clinic were followed from
      initiation of therapy until 24 weeks after the completion of therapy. Sustained
      virological response and rate of decline of HCV RNA levels were compared among
      patients with SSRI therapy and cytokine-related depression. RESULTS: Selective
      serotonin reuptake inhibitor therapy and cytokine-related depression did not
      adversely impact the proportion of patients achieving sustained virological
      response. In a multivariate longitudinal analysis, the mean slope of HCV RNA
      levels declined faster over time in patients without cytokine-related depression
      in comparison to patients with cytokine-related depression (P = 0.05), and the
      mean slope of HCV RNA levels declined similarly over time in patients with and
      without SSRI therapy. CONCLUSIONS: In this retrospective cohort, SSRI therapy did
      not interfere with immune activation dynamics of Peg-IFN/ribavirin, and patients
      without cytokine-related depression developed quicker responses and suppressed
      HCV replication more favorably over time.

PMID- 24135840
TI  - Hospitalization resource utilization and costs among Medicaid insured patients
      with schizophrenia with different treatment durations of long-acting injectable
      antipsychotic therapy.
AB  - This study evaluated the impact of using long-acting injectable (LAI)
      antipsychotics for a longer treatment duration versus a short duration on health
      care resource utilization among Medicaid-insured schizophrenia patients.
      Schizophrenia patients 13 years or older initiating LAI antipsychotics were
      identified from the Truven Health Analytics MarketScan Research Medicaid database
      between July 1, 2005, and June 30, 2010. The study population was grouped into 2
      study cohorts (longer-usage-duration cohort: >= 180 days of supply and short
      usage-duration cohort: <180 days of supply). Hospitalization-related resource
      utilization and costs were determined during a variable follow-up period and
      compared at the unadjusted and adjusted levels. Of the 5694 patients identified,
      2838 patients were treated with LAI antipsychotics for a mean duration of 604
      (SD, 432) days (mean age, 38.91 years), and 2856 were treated for 86 (SD, 43)
      days (mean age, 39.96 days). Total hospital lengths of stay, all cause (6.56 [SD,
      18.63] vs 4.93 [SD, 13.40] days, P < 0.001) and schizophrenia related (5.18 [SD,
      14.96] vs 4.16 [SD, 11.94] days, P = 0.005), and the mean number of
      hospitalizations, all cause (0.79 [SD, 1.78] vs 0.61 [SD, 1.41], P < 0.001) and
      schizophrenia related (0.63 [SD, 1.55] vs 0.51 [SD, 1.26], P = 0.001), were lower
      for the longer-usage-duration cohort. Cox regression results showed that using
      LAI antipsychotics for a longer duration was correlated with longer time to the
      first hospitalization for any cause and for schizophrenia. After multivariate
      regression, longer usage duration of LAI antipsychotics was associated with a
      decreased number of hospitalizations (-0.15 per year, P < 0.001), a decreased
      hospital length of stay (-1.50 days, P < 0.001), and reduced hospital payment (
      26%, P < 0.001). Patients who are treated with LAI antipsychotics for a longer
      versus shorter duration use hospital resources less.

PMID- 24135841
TI  - Effects of discontinuation of long-term used antipsychotics on prolactin and bone
      turnover markers in patients with intellectual disability.

PMID- 24135842
TI  - Restless legs syndrome associated with the combined use of quetiapine and
      venlafaxine.

PMID- 24135843
TI  - Risk of vaginal bleeding and postpartum hemorrhage after use of antidepressants
      in pregnancy: a study from the Norwegian Mother and Child Cohort Study.
AB  - This study aimed to examine obstetric bleeding outcomes after exposure during
      pregnancy to selective serotonin reuptake inhibitors (SSRIs), serotonin
      norepinephrine reuptake inhibitors (SNRIs), tricyclic (TCAs), and other
      antidepressants (OADs).The Norwegian Mother and Child Cohort Study and the
      Medical Birth Registry of Norway constituted the data source for the present
      study. We included 57,279 pregnant women, of which 1.02% reported use of
      antidepressants during pregnancy, mostly SSRIs/SNRIs (0.92%). We categorized
      exposure according to antidepressant use in pregnancy (SSRIs/SNRIs, n = 527;
      TCAs/OADs, n = 59; nonexposed, nondepressed, n = 55,411) with inclusion of a
      disease comparison group (nonexposed, depressed, n = 1282). We used logistic
      regression to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI)
      for vaginal bleeding outcomes in pregnancy and postpartum hemorrhage.Compared
      with nonexposed subjects, first trimester exposure to SSRIs/SNRIs or TCAs/OADs
      did not confer any increased risk of vaginal bleeding in early pregnancy (aOR,
      0.91; 95% CI, 0.72-1.16 and aOR, 0.83; 95% CI, 0.36-1.92, respectively). No
      increased risk for vaginal bleeding in midpregnancy was observed among users of
      SSRIs/SNRIs (aOR, 0.81; 95% CI, 0.50-1.31) or TCAs/OADs (aOR, 0.96; 95% CI, 0.26
      3.53) in second trimester. Exposure to SSRIs/SNRIs during gestational week 30 to
      childbirth did not confer any increased risk of postpartum hemorrhage after
      vaginal (aOR, 0.90; 95% CI, 0.47-1.74) or cesarean (aOR, 1.47; 95% CI, 0.51-4.22)
      delivery. Women in the disease comparison group presented a significant moderate
      increased risk of vaginal bleeding in early pregnancy (aOR, 1.22; 95% CI, 1.06
      1.39) and midpregnancy (aOR, 1.28; 95% CI, 1.07-1.55) but not postpartum.Among
      this Norwegian cohort of pregnant women, use of antidepressants in pregnancy was
      not associated with any obstetrical bleeding outcome.

PMID- 24135844
TI  - Inhaled thyrotropin-releasing hormone for treatment of neuropsychiatric
      disorders.

PMID- 24135845
TI  - Amphetamine increases errors during episodic memory retrieval.
AB  - Moderate doses of stimulant drugs are known to enhance memory encoding and
      consolidation, but their effects on memory retrieval have not been explored in
      depth. In laboratory animals, stimulants seem to improve retrieval of emotional
      memories, but comparable studies have not been carried out in humans. In the
      present study, we examined the effects of dextroamphetamine (AMP) on retrieval of
      emotional and unemotional stimuli in healthy young adults, using doses that
      enhanced memory formation when administered before encoding in our previous
      study. During 3 sessions, healthy volunteers (n = 31) received 2 doses of AMP (10
      and 20 mg) and placebo in counterbalanced order under double-blind conditions.
      During each session, they first viewed emotional and unemotional pictures and
      words in a drug-free state, and then 2 days later their memory was tested, 1 hour
      after AMP or placebo administration. Dextroamphetamine did not affect the number
      of emotional or unemotional stimuli remembered, but both doses increased recall
      intrusions and false recognition. Dextroamphetamine (20 mg) also increased the
      number of positively rated picture descriptions and words generated during free
      recall. These data provide the first evidence that therapeutic range doses of
      stimulant drugs can increase memory retrieval errors. The ability of AMP to
      positively bias recollection of prior events could contribute to its potential
      for abuse. 

PMID- 24135846
TI  - Expression of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in
      sacral chordoma.
AB  - Sacral chordoma is a rare and aggressive tumor, with a high rate of local
      recurrence even when the tumor is radically resected. The fundamental knowledge
      of its biological behavior remains unknown. Insulin-like growth factor II mRNA
      binding protein 3 (IMP3) is one of the RNA binding proteins and is expressed
      during embryogenesis and in various malignant tumors. This study evaluated
      expression of IMP3 in sacral chordoma for association with patient's
      clinicopathological factors. A total of 32 patients with sacral chordoma (17 male
      and 15 female) and 10 samples of distant normal tissues were collected for
      analysis of IMP3 expression using immunohistochemistry. Association between IMP3
      expression and clinicopathological factors (such as patient's age, gender, tumor
      location, tumor size, surrounding muscle invasion, Ki-67 expression, and tumor
      recurrence) were statistically analyzed. IMP3 was expressed in 20 (62.5%)
      patients, whereas there was no expression in the 10 distant normal tissues. IMP3
      expression was associated with tumor invasion into the surrounding muscle (P =
      0.028), high levels of Ki-67 expression (P = 0.009), and tumor recurrence (P =
      0.012). The log-rank test revealed that patients with positive IMP3 expression
      had a shorter continuous disease-free survival time than those with negative IMP3
      expression (P = 0.016). IMP3 expression was independent of age, gender, tumor
      location and tumor size. These results indicate that IMP3 was overexpressed in
      sacral chordoma and this expression was associated with tumor invasion and
      recurrence; thus, IMP3 may play an important role in tumor progression and could
      serve as a prognostic biomarker for sacral chordoma and IMP3 could be used as a
      potential therapeutic target for the treatment of sacral chordoma.

PMID- 24135847
TI  - Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor
      recurrence in prolactinomas.
AB  - Prolactinomas, or prolactin-secreting adenomas, constitute the most common type
      of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line
      medication for prolactinomas, but the tumors are resistant to the therapy in 5-18
      % of patients. To explore potential mechanisms of resistance to bromocriptine (a
      dopamine agonist), we analyzed six responsive prolactinomas and six resistant
      prolactinomas by whole-exome sequencing. We identified ten genes with sequence
      variants that were differentially found in the two groups of tumors. The
      expression of these genes was then quantified by real-time reverse-transcription
      PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The
      mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant
      prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3
      expression was also associated with tumor recurrence. Our results suggest that
      low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor
      recurrence of prolactinomas. 

PMID- 24135848
TI  - Factors associated with a higher rate of distant failure after primary treatment
      for glioblastoma.
AB  - Our purpose was to analyze the pattern of failure in glioblastoma (GBM) patients
      at first recurrence after radiotherapy and temozolomide and its relationship with
      different factors. From 77 consecutive GBM patients treated at our institution
      with fluorescence guided surgery and standard radiochemotherapy, 58 first
      recurrences were identified and included in a retrospective review. Clinical data
      including age, Karnofsky performance score, preoperative tumor volume and
      location, extend of resection, MGMT promoter methylation status, time to
      progression (PFS), overall survival (OS) and adjuvant therapies were reviewed for
      every patient. Recurrent tumor location respect the original lesion was the end
      point of the study. The recurrence pattern was local only in 65.5% of patients
      and non-local in 34.5%. The univariate and multivariate analysis showed that
      greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the
      only variable with statistical signification (p < 0.001) for increased rate of
      non-local recurrences, although patients with MGMT methylation and complete
      resection of enhancing tumor presented non-local recurrences more frequently. PFS
      was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p =
      0.019, log-rank). However, OS was not significantly different in both groups
      (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences in our
      series of patients treated with fluorescence guided surgery and standard
      radiochemotherapy was higher than previously published in GBM, especially in
      patients with longer PFS. Greater preoperative enhancing tumor volume was
      associated with increased rate of non-local recurrences.

PMID- 24135850
TI  - Utilization of cytoreductive nephrectomy and patient survival in the targeted
      therapy era.
AB  - We sought to analyze utilization and survival outcomes of cytoreductive
      nephrectomy (CN) in patients with metastatic renal cell carcinoma (RCC) before
      and after introduction of targeted therapy. We identified patients with
      metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal
      trends in utilization. We performed a joinpoint regression to determine when
      changes in utilization of CN occurred. We fitted multivariable proportional
      hazard models in full and propensity score-matched cohorts. We performed a
      difference-in-difference analysis to compare survival outcomes before and after
      introduction of targeted therapy. The proportion of patients undergoing CN
      increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint
      of 2004, just prior to the introduction of targeted therapy. Beginning in 2005,
      there was a modest decrease in utilization of CN. CN was associated with a lower
      adjusted relative hazard (0.41, 95% confidence interval 0.34-0.43). Median
      survival among patients receiving CN increased in the targeted therapy era (19
      vs. 13 months), while median survival among patients not receiving CN increased
      only slightly (4 vs. 3 months). Difference-in-difference analysis showed a
      significant decrease in hazard of death among patients who received CN in the
      targeted therapy era. Despite decreased utilization in the targeted therapy era,
      CN remains associated with improved survival. Prospective randomized trials are
      needed to confirm the benefit of CN among patients with metastatic RCC treated
      with novel targeted therapies.

PMID- 24135851
TI  - A morphological study of anatomical plates for acetabular posterior column.
AB  - PURPOSES: The objective of this work is to explore the morphological
      characteristics of the acetabular posterior column using digital technology, in
      order to develop anatomical plates for internal fixation of acetabular posterior
      column fractures. MATERIALS AND METHODS: Three-dimensional reconstruction models
      of the pelvis were developed from computed tomography scan data of 111 adult
      patients. From them, the diameter (D) of the femoral head, three approximate arcs
      along the acetabular posterior column plate path with corresponding radius of
      curvature [Formula: see text] and [Formula: see text], as well as an angle
      [Formula: see text] were measured. A statistical analysis was used to determine
      the most feasible method of designing anatomical plates according to the data.
      RESULTS: The statistical analysis results showed that [Formula: see text] and
      [Formula: see text] had no correlations with D, and they also exhibited no
      statistically significant differences between genders. By examining the
      correlations between four morphological parameters of the acetabular posterior
      column, the results showed [Formula: see text] increased along with [Formula: see
      text] was inversely proportional to [Formula: see text] and [Formula: see text],
      and [Formula: see text] was independent with little variation. Taking [Formula:
      see text] as the reference, the data were divided into three groups and three
      types of anatomical plates were designed according to the three groups of data.
      CONCLUSION: The anatomical structure of the acetabular posterior column exhibits
      great individual differences. Anatomical plates designed in this study have
      higher accuracy than those conventional ones, which is helpful to the quality of
      fracture reduction and reduce the operation difficult. Meanwhile, they also can
      be conveniently used in clinic.

PMID- 24135849
TI  - Regulatory crosstalk within the mammalian unfolded protein response.
AB  - Increased demands on the protein folding capacity of the endoplasmic reticulum
      (ER) trigger the unfolded protein response (UPR). Comprised of a tripartite
      signaling system, the UPR regulates translation and gene transcription to
      manifest pro-adaptive and, if necessary, pro-apoptotic outcomes. The three UPR
      pathways, initiated by activating transcription factor 6, inositol requiring
      enzyme 1, and protein kinase RNA-activated-like ER kinase (PERK), direct distinct
      downstream signaling events. However, it is becoming increasingly clear that
      interplay between the cascades is vital in shaping the UPR. In particular, recent
      discoveries have revealed that PERK-dependent signals mediate both inter- and
      intra-pathway regulation within the UPR, underscoring the critical role of the
      PERK pathway in the cellular response to ER stress. 

PMID- 24135852
TI  - True four-dimensional analysis of thoracic aortic displacement and distension
      using model-based segmentation of computed tomography angiography.
AB  - Previous analyses of aortic displacement and distension using computed tomography
      angiography (CTA) were performed on double-oblique multi-planar reformations and
      did not consider through-plane motion. The aim of this study was to overcome this
      limitation by using a novel computational approach for the assessment of thoracic
      aortic displacement and distension in their true four-dimensional extent. Vessel
      segmentation with landmark tracking was executed on CTA of 24 patients without
      evidence of aortic disease. Distension magnitudes and maximum displacement
      vectors (MDV) including their direction were analyzed at 5 aortic locations: left
      coronary artery (COR), mid-ascending aorta (ASC), brachiocephalic trunk (BCT),
      left subclavian artery (LSA), descending aorta (DES). Distension was highest for
      COR (2.3 +/- 1.2 mm) and BCT (1.7 +/- 1.1 mm) compared with ASC, LSA, and DES (p
      < 0.005). MDV decreased from COR to LSA (p < 0.005) and was highest for COR (6.2
      +/- 2.0 mm) and ASC (3.8 +/- 1.9 mm). Displacement was directed towards left and
      anterior at COR and ASC. Craniocaudal displacement at COR and ASC was 1.3 +/- 0.8
      and 0.3 +/- 0.3 mm. At BCT, LSA, and DES no predominant displacement direction
      was observable. Vessel displacement and wall distension are highest in the
      ascending aorta, and ascending aortic displacement is primarily directed towards
      left and anterior. Craniocaudal displacement remains low even close to the left
      cardiac ventricle.

PMID- 24135853
TI  - Glutathione homeostasis disruption of erythrocytes, but not glutathione
      peroxidase activity change, is closely accompanied with neurological and
      radiological scoring of acute CNS inflammation.
AB  - OBJECTIVES AND METHODS: The levels of glutathione (GSH) and glutathione
      peroxidase (GPx) activity were measured in the erythrocytes of 50 patients with
      clinically isolated syndrome of CNS (CIS) and 57 patients with relapsing
      remitting multiple sclerosis (RRMS). RESULTS: A decrease in GSH content and GPx
      activity showed significance in both study groups compared to the control values
      (p = 0.0025 and 0.007 for GSH and p = 0.005 and 0.003 for GPx, in CIS and RRMS
      patients, respectively). The depletions were more pronounced in RRMS than in CIS
      patients (p = 0.009 for GSH and p = 0.031 for GPx). The results significantly
      verify the negative correlations between GSH values and clinical severity (r = 
      0.513, p = 0.004), radiological findings (r = -0.351, p = 0.008) and disease
      duration (r = -0.412, p = 0.0025) in CIS patients. The same correlations were
      observed in RRMS patients between GSH values and clinical severity (r = -0.498, p
      = 0.004) and patients' radiological features (r = -0.454, p = 0.005). No
      correlations were observed between GSH values and other patient characteristics,
      or between GPx activity and all tested patient characteristics (p > 0.01).
      CONCLUSIONS: The results indicate that GSH content and GPx activity both
      decreased below the normal range and were accompanied with neuroinflammation, but
      although both might have great importance in neuroinflammation development, the
      data presented here confirm that only GSH might serve as a marker which is
      closely correlated with neurological and radiological scoring of acute CNS
      inflammation.

PMID- 24135854
TI  - There is no universal mechanism for the cleavage of RNA model compounds in the
      presence of metal ion catalysts.
AB  - The transesterification of uridine 3'-phosphodiesters with a wide range of
      leaving group alcohols has been studied in the presence of monometallic and
      bimetallic complexes. The catalysis of isomerization of the phosphodiester bond
      was studied with a nucleoside 3'-phosphonate as a substrate. The results obtained
      are consistent with a step-wise mechanism, where metal ions are able to enhance
      both the nucleophilic attack and the departure of the leaving group. The
      mechanism of the catalysis depends on the acidity of the catalyst and of the
      leaving group alcohol: a change from general base catalysis to general acid
      catalysis is proposed. Catalysis of the isomerization requires efficient
      stabilization of the phosphorane by strong interactions with the catalyst.
      Catalytic strategies utilised by bimetallic complexes are also briefly discussed.

PMID- 24135855
TI  - Repositioning of the anthelmintic drug mebendazole for the treatment for colon
      cancer.
AB  - PURPOSE: In the present study, we screened a compound library containing 1,600
      clinically used compounds with the aim to identify compounds, which potentially
      could be repositioned for colon cancer therapy. METHODS: Two established colon
      cancer cell lines were tested using the fluorometric microculture cytotoxicity
      assay (FMCA). For compound comparison connectivity map (CMAP) analysis, NCI 60
      data mining and protein kinase binding measurements were performed. RESULTS:
      Sixty-eight compounds were defined as hits with activity in both of these cell
      lines (<40 % cell survival compared with control) at 10 MUM drug concentration.
      Analysis of chemical similarity of the hit compounds revealed several distinct
      clusters, among them the antiparasitic benzimidazole group. Two of these
      compounds, mebendazole (MBZ) and albendazole (ABZ) are registered for human use.
      Data from the NCI 60 cell line panel revealed only modest correlation between MBZ
      and ABZ, indicating differences in mechanism of action. This was further
      supported when gene expression signatures were compared in the CMAP database; ABZ
      ranked very low when MBZ was used as the query signature. Furthermore, MBZ, but
      not ABZ, was found to significantly interact with several protein kinases
      including BCR-ABL and BRAF. Analysis of the diagnosis-specific activity of MBZ
      showed activity in 80 % of the colon cancer cell lines in the NCI 60 panel. Three
      additional colon cancer cell lines and three cell models with non-malignant
      phenotypes were subsequently tested, confirming selective colon cancer activity
      of MBZ. CONCLUSION: MBZ seemingly has repositioning potential for colorectal
      cancer therapy.

PMID- 24135856
TI  - A chemical reaction controlled mechanochemical route to construction of CuO
      nanoribbons for high performance lithium-ion batteries.
AB  - We reported a chemical reaction controlled mechanochemical route to synthesize
      mass CuO nanosheets by manual grinding in a mortar and pestle, which does not
      require any solvent, complex apparatus and techniques. The activation of chemical
      reactions by milling reactants was thus proved, and the energy from mechanical
      grinding promotes the fast formation of CuO nanoribbons. The resultant materials
      have preferential nanoscale ribbon-like morphology that can show large capacity
      and high cycle performance as lithium-ion battery anodes. After 50 cycles, the
      discharge capacity of CuO nanoribbon electrodes is 614.0 mA h g(-1), with 93%
      retention of the reversible capacity. The thermodynamic reactions of the CuO
      battery showed size-dependent characterization. The microstructures of CuO
      nanosheets and reaction routes can be controlled by the ratio of NaOH/CuAc2
      according to the chemical reactions involved. The intact nanoribbon structure,
      thin-layer, and hierarchical structures endow present CuO materials with high
      reversible capacity and excellent cycling performances. The simple, economical,
      and environmentally friendly mechanochemical route is of great interest in modern
      synthetic chemistry. 

PMID- 24135857
TI  - Hypoconnectivity and hyperfrontality in retired American football players.
AB  - Recent research has raised concerns about the long-term neurological consequences
      of repetitive concussive and sub-concussive injuries in professional players of
      American Football. Despite this interest, the neural and psychological status of
      retired players remains unknown. Here, we evaluated the performances and brain
      activation patterns of retired National Football League players (NFL alumni)
      relative to controls using an fMRI-optimised neuropsychological test of executive
      function. Behaviourally, the NFL alumni showed only modest performance deficits
      on the executive task. By contrast, they showed pronounced hyperactivation and
      hypoconnectivity of the dorsolateral frontal and frontopolar cortices.
      Critically, abnormal frontal-lobe function was correlated with the number of
      times that NFL alumni reported having been removed from play after head injury
      and was evident in individual players. These results support the hypothesis that
      NFL alumni have a heightened probability of developing executive dysfunction and
      suggest that fMRI provides the most sensitive biomarker of the underlying neural
      abnormality. 

PMID- 24135858
TI  - Pattern of antioxidant enzyme activities and hydrogen peroxide content during
      developmental stages of rhizogenesis from hypocotyl explants of Mesembryanthemum
      crystallinum L.
AB  - KEY MESSAGE: H2O2 is necessary to elicit rhizogenic action of auxin. Activities
      of specific catalase and manganese superoxide dismutase forms mark roots
      development. Hypocotyl explants of Mesembryanthemum crystallinum regenerated
      roots on medium containing 2,4-dichlorophenoxyacetic acid. Explants became
      competent to respond to the rhizogenic action of auxin on day 3 of culture, when
      hydrogen peroxide content in cultured tissue was the highest. L-Ascorbic acid
      added to the medium at 5 MUM lowered the H2O2 level, inhibited rhizogenesis and
      induced non-regenerative callus, suggesting that certain level of H2O2 is
      required to promote root initiation. Coincident with the onset of rhizogenic
      determination, meristemoids formed at the periphery of the hypocotyl stele and
      the activity of the manganese form of superoxide dismutase, MnSOD-2 was induced.
      Once induced, MnSOD-2 activity was maintained through the post-determination
      phase of rooting, involving root growth. MnSOD-2 activity was not found in non
      rhizogenic explants maintained in the presence of AA. Analyses of the maximum
      photochemical efficiency of photosystem II and the oxygen uptake rate revealed
      that the explants were metabolically arrested during the predetermination stage
      of rhizogenesis. Respiratory and photosynthetic rates were high during root
      elongation and maturation. Changes in catalase and peroxidase activities
      correlated with fluctuations of endogenous H2O2 content throughout rhizogenic
      culture. Expression of a specific CAT-2 form accompanied the post-determination
      stage of rooting and a high rate of carbohydrate metabolism during root growth.
      On the other hand, the occurrence of MnSOD-2 activity did not depend on the
      metabolic status of explants. The expression of MnSOD-2 activity throughout root
      development seems to relate it specifically to root metabolism and indicates it
      as a molecular marker of rhizogenesis in M. crystallinum.

PMID- 24135859
TI  - Reappraisal of the vascular anatomy of the colon and consequences for the
      definition of surgical resection.
AB  - INTRODUCTION: Databases of information on surgical treatment for colorectal
      cancer have been created in various countries and data have started to be
      released. The most important facets of research for statistical processing
      include the methodology and firm definitions of content. However, for trials
      involving colorectal cancer, the applicable terminology has not been defined, and
      much bias is frequently encountered. Starting from definitions of the colon and
      vascular system of the colon, we propose definitions of surgical procedures for
      colorectal cancer. METHODOLOGY: This paper reviews the colon segments and
      vascular anatomy of the colon. If surgical treatment of colon cancer is
      considered from this perspective, we can see that definitions for these surgical
      procedures are lacking. The definition of surgical treatment would also allow
      clarification of the range of lymph node dissection. In general, surgical
      procedures and the area of surgical lymph node dissection are both defined
      according to the basic structure of the associated arteries. However, the
      existing descriptions are not based on a definition of the arteries. We therefore
      tried to establish the most useful nomenclature for the arterial system of the
      large intestine for colorectal surgeons and reviewed the frequency of important
      arterial variations. Using the resulting definitions, we provided consistent
      definitions for colon cancer surgery. CONCLUSION: The segments of the colon need
      to be defined. In surgery, procedures are performed using the arteries as
      indicators, so vessels originating from the superior and inferior mesenteric
      arteries are referred to as arteries, with others are referred to as branches.
      Surgical treatment of colon cancer can be defined from the relationship between
      these arteries. For the first time, this may allow proper application of
      statistics for the treatment of colon cancer.

PMID- 24135860
TI  - Trends and outcomes for donor oocyte cycles in the United States, 2000-2010.
AB  - IMPORTANCE: The prevalence of oocyte donation for in vitro fertilization (IVF)
      has increased in the United States, but little information is available regarding
      maternal or infant outcomes to improve counseling and clinical decision making.
      OBJECTIVES: To quantify trends in donor oocyte cycles in the United States and to
      determine predictors of a good perinatal outcome among IVF cycles using fresh
      (noncryopreserved) embryos derived from donor oocytes. DESIGN, SETTING, AND
      PARTICIPANTS: Analysis of data from the Centers for Disease Control and
      Prevention's National ART Surveillance System, to which fertility centers are
      mandated to report and which includes data on more than 95% of all IVF cycles
      performed in the United States. Data from 2000 to 2010 described trends. Data
      from 2010 determined predictors. MAIN OUTCOMES AND MEASURES: Good perinatal
      outcome, defined as a singleton live-born infant delivered at 37 weeks or later
      and weighing 2500 g or more. RESULTS: From 2000 to 2010, data from 443 clinics
      (93% of all US fertility centers) were included. The annual number of donor
      oocyte cycles significantly increased, from 10,801 to 18,306. Among all donor
      oocyte cycles, an increasing trend was observed from 2000 to 2010 in the
      proportion of cycles using frozen (vs fresh) embryos (26.7% [95% CI, 25.8%-27.5%]
      to 40.3% [95% CI, 39.6%-41.1%]) and elective single-embryo transfers (vs transfer
      of multiple embryos) (0.8% [95% CI, 0.7%-1.0%] to 14.5% [95% CI, 14.0%-15.1%]).
      Good perinatal outcomes increased from 18.5% (95% CI, 17.7%-19.3%) to 24.4% (95%
      CI, 23.8%-25.1%) (P < .001 for all listed trends). Mean donor and recipient ages
      remained stable at 28 (SD, 2.8) years and 41 (SD, 5.3) years, respectively. In
      2010, 396 clinics contributed data. For donor oocyte cycles using fresh embryos
      (n = 9865), 27.5% (95% CI, 26.6%-28.4%) resulted in good perinatal outcome.
      Transfer of an embryo at day 5 (adjusted odds ratio [OR], 1.17 [95% CI, 1.04
      1.32]) and elective single-embryo transfers (adjusted OR, 2.32 [95% CI, 1.92
      2.80]) were positively associated with good perinatal outcome; tubal (adjusted
      OR, 0.72 [95% CI, 0.60-0.86]) or uterine (adjusted OR, 0.74 [95% CI, 0.58-0.94])
      factor infertility and non-Hispanic black recipient race/ethnicity (adjusted OR,
      0.48 [95% CI, 0.35-0.67]) were associated with decreased odds of good outcome.
      Recipient age was not associated with likelihood of good perinatal outcome.
      CONCLUSIONS AND RELEVANCE: In the United States from 2000 to 2010, there was an
      increase in number of donor oocyte cycles, accompanied by an increase in good
      outcomes. Further studies are needed to understand the mechanisms underlying the
      factors associated with less successful outcomes.

PMID- 24135861
TI  - The impact of paternity leave on fathers' future earnings.
AB  - Using Norwegian registry data, we investigate the effect of paternity leave on
      fathers' long-term earnings. If the paternity leave increased long-term father
      involvement, then we should expect a reduction in fathers' long-term earnings as
      they shift time and effort from market to home production. For identification, we
      use the Norwegian introduction of a paternity-leave quota in 1993, reserving four
      weeks of the total of 42 weeks of paid parental leave exclusively for the father.
      The introduction of the paternity-leave quota led to a sharp increase in rates of
      leave-taking for fathers. We estimate a difference-in-differences model that
      exploits differences in fathers' exposure to the paternity-leave quota by the
      child's age and year of observation. Our analysis suggests that four weeks of
      paternity leave during the child's first year decreases fathers' future earnings,
      an effect that persists through our last point of observation, when the child is
      5 years old. A battery of robustness tests supports our results.

PMID- 24135862
TI  - SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia.
AB  - Idiopathic basal ganglia calcification (IBGC) is characterized by bilateral
      calcification of the basal ganglia associated with a spectrum of neuropsychiatric
      and motor syndromes. In this study, we set out to determine the frequency of the
      recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic
      Florida Brain Bank using both Sanger sequencing and TaqMan copy number analysis
      to cover the complete spectrum of possible mutations. We identified SLC20A2
      pathogenic mutations in two of the 27 cases of IBGC (7 %). Sequencing analysis
      identified a p.S113* nonsense mutation in SLC20A2 in one case. TaqMan copy number
      analysis of SLC20A2 further revealed a genomic deletion in a second case, which
      was part of a large previously reported Canadian IBGC family with dystonia.
      Subsequent whole-genome sequencing in this family revealed a 563,256-bp genomic
      deletion with precise breakpoints on chromosome 8 affecting multiple genes
      including SLC20A2 and the known dystonia-related gene THAP1. The deletion co
      segregated with disease in all family members. The deletion of THAP1 in addition
      to SLC20A2 in the Canadian IBGC family may contribute to the severe and early
      onset dystonia in this family. The identification of an SLC20A2 genomic deletion
      in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of
      mutant protein is sufficient to cause neurodegeneration and that previously
      reported SLC20A2 mutation frequencies may be underestimated. 

PMID- 24135863
TI  - Contribution of vasoactive intestinal peptide to immune homeostasis in
      trophoblast-maternal leukocyte interaction under LPS stimulation.
AB  - BACKGROUND/AIMS: The maternal-fetal interface is a unique immunological site that
      generates an adequate microenvironment during pregnancy, recognizing and
      eliminating infections and tolerating the trophoblast/placenta unit. For that
      purpose, trophoblast cells display several tolerogenic mechanisms to allow fetal
      survival, such as production of the neuropeptide vasoactive intestinal peptide
      (VIP). Here we investigated the contribution of VIP to maintain homeostasis at
      the maternal-placental interface under lipopolysaccharide (LPS) stimulation.
      METHODS: We performed cocultures between trophoblast cells (Swan-71 cell line)
      and maternal leukocytes obtained from fertile women as an in vitro model of
      maternal-placental interaction, and we focused on the effects of LPS on the
      modulation of VIP and their receptors (VPAC1 and VPAC2). RESULTS: VIP could
      prevent the upregulation of IL-6, MCP-1, and nitrite production and maintain the
      production of IL-10 and TGF-beta under LPS (10 ug/ml) stimulation after 48 h of
      coculture. To gain deeper insight into the mechanisms of how VIP could contribute
      to a tolerogenic microenvironment even in the presence of LPS, we investigated
      VIP production by maternal leukocytes and observed a significant increase in the
      frequency of CD4+VIP+ cells after interaction with Swan-71 cells in the presence
      of LPS. LPS increased VIP and inducible receptor VPAC2 expression directly on
      trophoblast cells in a dose- and time-dependent manner. CONCLUSIONS: The present
      results suggest that VIP might act as an additional homeostatic mechanism during
      early stages at the maternal-placental interface to control exacerbated
      inflammatory responses such as the ones observed in intrauterine infections.

PMID- 24135864
TI  - In situ engineering of NanoBud geometries.
AB  - NanoBuds exist in a variety of stable structures. Our studies show that
      engineering NanoBud geometries is indeed possible and we visualise the
      transformation of one Nanobud geometry to another using in situ aberration
      corrected imaging techniques. Such NanoBuds are precursors for generating
      nanotube junctions which could be used in composite and electronic applications. 

PMID- 24135865
TI  - Distribution and pollution, toxicity and risk assessment of heavy metals in
      sediments from urban and rural rivers of the Pearl River delta in southern China.
AB  - Sediments were collected from the upper, middle and lower reaches of both urban
      and rural rivers in a typical urbanization zone of the Pearl River delta. Six
      heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) were analyzed in all sediment samples,
      and their spatial distribution, pollution levels, toxicity and ecological risk
      levels were evaluated to compare the characteristics of heavy metal pollution
      between the two rivers. Our results indicated that the total contents of the six
      metals in all samples exceeded the soil background value in Guangdong province.
      Based on the soil quality thresholds of the China SEPA, Cd levels at all sites
      exceeded class III criteria, and other metals exhibited pollution levels
      exceeding class II or III criteria at both river sites. According to the sediment
      quality guidelines of the US EPA, all samples were moderately to heavily polluted
      by Cr, Cu, Ni, Pb and Zn. Compared to rural river sites, urban river sites
      exhibited heavier pollution. Almost all sediment samples from both rivers
      exhibited moderate to serious toxicity to the environment, with higher
      contributions from Cr and Ni. A "hot area" of heavy metal pollution being
      observed in the upper and middle reaches of the urban river area, whereas a "hot
      spot" was identified at a specific site in the middle reach of the rural river.
      Contrary metal distribution patterns were also observed along typical sediment
      profiles from urban and rural rivers. However, the potential ecological risk
      indices of rural river sediments in this study were equal to those of urban river
      sediments, implying that the ecological health issues of the rivers in the
      undeveloped rural area should also be addressed. Sediment organic matter and
      grain size might be important factors influencing the distribution profiles of
      these heavy metals. 

PMID- 24135866
TI  - Whole-transcriptome analysis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of death in the
      world. It involves a complicated pathogenesis. In the present study, we tried to
      uncover the underlying mechanisms from the RNA level. Whole-transcriptome
      analysis using RNA-seq data showed that the tumor cells had higher expression
      levels of genes compared to normal tissue cells, with much more genes related to
      metabolism, synthesis, and transportation. A total of 4,638 differentially
      expressed genes were obtained in HCC, in which 3,476 were up-regulated and 1,162
      were down-regulated. A total of 2,367 new isoforms and 46 fusion genes were
      detected in HCC cells using computational method. Within these variants, new
      isoforms of NIR and fusion genes PARP15-AHSG caught our attention for their
      potential roles in cancer development. These findings could be beneficial in
      guiding future researches. 

PMID- 24135867
TI  - An effective reinduction regimen for first relapse of adult acute lymphoblastic
      leukemia.
AB  - Current salvage regimens achieve complete remission (CR) in about a third of
      adults with relapsed/refractory acute lymphoblastic leukemia (ALL), and this
      represents a major barrier for performing allogeneic hematopoietic stem cell
      transplant (HSCT), the only potentially curative treatment. We conducted in
      adults with first relapse of ALL, a prospective clinical trial with intensive
      regimen derived from the pediatric Berlin-Frankfurt-Muenster-85 protocol, with
      addition of a continuous infusional multi-agent chemotherapy in phase II
      induction followed by consolidation with alternating monthly cycles. Objectives
      of this study included CR rate, leukemia-free survival (LFS) and toxicity of the
      regimen in adults. We report the outcome of 19 patients (19-51 years of age)
      treated prospectively on the study, as well as a subsequent cohort of 31 patients
      (18-53 years of age) treated off the study. Thirteen of 19 (68%) patients from
      the initial prospective study achieved CR, and the median overall survival (OS)
      of these 13 CR patients was 10.3 months. The median OS and LFS of all 19 patients
      were 5.6 and 4.3 months, respectively. The regimen was well tolerated, and no
      grade 4 non-hematological toxicity was observed. Of the 31 patients treated off
      the study and analyzed retrospectively, 16 (52%) achieved CR. After including all
      50 patients, the CR rate was 58%. The regimen used in this trial appears to be
      feasible and effective salvage therapy option for adult patients younger than age
      55 with relapsed ALL, produced a high CR rate and could facilitate subsequent
      allogeneic HSCT.

PMID- 24135868
TI  - High level of serum AMBP is associated with poor response to paclitaxel
      capecitabine chemotherapy in advanced gastric cancer patients.
AB  - Gastric cancer is one of the most common human cancers and ranks the second in
      the global cancer-related mortality. The clinical outcome of patients with
      advanced gastric cancer (AGC) is markedly dependent on their response to the
      chemotherapy. Paclitaxel plus capecitabine, as a first-line regimen, is widely
      administrated in AGC patients, but more than a half of the patients have a poor
      response, possibly due to their resistance to the treatment. Therefore, it is
      important to identify potential responders to improve the efficacy of the
      chemotherapy. In the present study, we used an isobaric tag approach for relative
      and absolute quantification combined with ESI-QUAD-TOF/MS to identify potential
      predictive biomarkers for the chemotherapy. We found 211 serum proteins, and
      confirmed 17 candidates that were differentially present in the progression of
      disease (PD) group and the partial response (PR) group to the treatment of
      paclitaxel plus capecitabine. In further validation of the 17 candidates in the
      set of 12 PD and 12 PR AGC patients, we identified a higher level of AMBP (Alpha
      1-Microglobulin/Bikunin Precursor) in the sera of PD patients than of the PR
      patients assayed by ELISA (9.13 +/- 0.45 vs. 8.11 +/- 0.26 MUg/mL, p = 0.06) and
      by the Western blotting (relative gray value 396.4 +/- 39.1 vs. 275.0 +/- 34.76,
      p = 0.03), respectively. The receiver operating characteristics curve showed 75%
      sensitivity and 75% specificity of AMBP in AGC patients treated with the
      chemotherapy. Our data indicated that the high level of serum AMBP could predict
      the poor response of the AGC patients treated with the paclitaxel-capecitabine
      chemotherapy, which could be used as a potential biomarker to identify patients
      who would benefit from this chemotherapeutic regimen.

PMID- 24135870
TI  - Cysteine protease is a major component in the excretory/secretory products of
      Euclinostomum heterostomum (Digenea: Clinostomidae).
AB  - Cysteine proteases of parasite organisms play numerous indispensable roles in
      tissue penetration, feeding, immunoevasion, virulence, egg hatching and
      metacercarial excystment. They are critical key enzymes in the biology of
      parasites and have been exploited as serodiagnostic markers, therapeutic and
      vaccine targets. In the present study, the cysteine proteases in the in vitro
      released excretory/secretory (E/S) products of the digenetic trematode parasite,
      Euclinostomum heterostomum have been analysed. The encysted progenetic
      metacercariae of E. heterostomum collected from the infected liver and kidney of
      Channa punctatus were excysted in vitro and incubated in phosphate buffer at 37
      +/- 1  degrees C, and the E/S products released were analysed. The
      spectrophotometric analysis of the proteases revealed active hydrolysis of
      chromogenic substrate, azocoll, in a time-, temperature- and pH-dependent manner.
      Optimum activity was observed at pH 7.0 at 37 +/- 1  degrees C, and with 1 mM
      each of various protease inhibitors (Mini Protease Inhibitor Cocktail, ethylene
      diaminetetraacetic acid, phenyl methyl sulphonyl fluoride, iodoacetamide and 1,10
      phenanthroline) used, significant inhibition was observed by iodoacetamide and
      85% of inhibition at a concentration of 2 mM, suggesting that cysteine protease
      is a major component in the E/S of this parasite. Four discrete protease bands of
      Mr 36, 39, 43 and 47 kDa were identified by gelatin-substrate zymography. Maximum
      gelatinolytic activity was observed at pH 7.0, and among various inhibitors used,
      almost complete disappearance of protease bands was observed by 2 mM
      iodoacetamide. The proteolytic cleavage of bovine serum albumin, bovine
      haemoglobin and human haemoglobin in vitro were also studied.

PMID- 24135871
TI  - Temporal and spatial changes in the composition and structure of helminth
      component communities in European eels Anguilla anguilla in an Adriatic coastal
      lagoon and some freshwaters in Italy.
AB  - The composition and diversity of the helminth component communities in eels
      Anguilla anguilla were determined in three separate localities in Italy: an
      Adriatic coastal lagoon, Comacchio and two freshwater localities, the River Po
      and the Lake Piediluco. Data from Comacchio lagoon were analysed over 15 years to
      determine whether community composition and diversity changed significantly
      overtime. The community was species rich (nine species, all marine except
      Proteocephalus macrocephalus) and was dominated by a suite of digeneans:
      Deropristis inflata, Helicometra fasciata, Lecithochirium musculus and Bucephalus
      anguillae. The community showed little change in composition over the period, but
      the relative abundance and dominance of the species did alter. By contrast, the
      component communities in the freshwater localities were species poor and the
      dominant species were freshwater acanthocephalans, Pomphorhyncus laevis in River
      Po and Acanthocephalus rhinensis in Lake Piediluco. The helminth community of
      Lake Piediluco with five species was richer than that of the River Po with only
      three species, but was poorer than that of Comacchio lagoons. Similarity indices
      between samples from Comacchio were high; between the lagoon and the freshwater
      localities and between the two freshwater localities, similarity indices were
      very low. Helminth component community structure in coastal lagoons was
      comparable across Europe. The helminth community in the River Po was similar to
      those in the River Tiber and other European rivers whilst that in Lake Piediluco
      was similar to that in other European lakes. Levels of the pathogenic
      Anguillicoloides crassus in swim bladders were consistently lower in prevalence
      and abundance in the coastal lagoons than in freshwater localities. This suggests
      that this parasite may have little impact on migrating eels if they are indeed
      primarily of marine origin and so it may be of little importance in the recent
      decline of eel populations throughout Europe.

PMID- 24135872
TI  - Crosstalk between beta-catenin and snail in the induction of epithelial to
      mesenchymal transition in hepatocarcinoma: role of the ERK1/2 pathway.
AB  - Epithelial to mesenchymal transition (EMT) is an integral process in the
      progression of many epithelial tumors. It involves a coordinated series of
      events, leading to the loss of epithelial features and the acquisition of a
      mesenchymal phenotype, resulting in invasion and metastasis. The EMT of
      hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic
      dissemination and distal metastasis. In this study, we used 12-O-tet
      radecanoylphorbol-13-acetate (TPA) to dissect the signaling pathways involved in
      the EMT of HepG2 hepatocarcinoma cells. The spectacular change in phenotype
      induced by TPA, leading to a pronounced spindle-shaped fibroblast-like cell
      morphology, required ERK1/2 activation. This ERK1/2-dependent EMT process was
      characterized by a loss of E-cadherin function, modification of the cytoskeleton,
      the acquisition of mesenchymal markers and profound changes to extracellular
      matrix composition and mobility. Snail was essential for E-cadherin repression,
      but was not sufficient for full commitment of the TPA-triggered EMT. We found
      that TPA triggered the formation of a complex between Snail and beta-catenin that
      activated the Wnt pathway. This study thus provides the first evidence for the
      existence of a complex network governed by the ERK1/2 signaling pathway,
      converging on the coregulation of Snail and the Wnt/beta-catenin pathway and
      responsible for the onset and the progression of EMT in hepatocellular carcinoma
      cells. 

PMID- 24135874
TI  - Ultrastructural analysis of nanogold-labeled cell surface microvilli in liquid by
      atmospheric scanning electron microscopy and their relevance in cell adhesion.
AB  - The adhesion of leukocytes circulating in the blood to vascular endothelium is
      critical for their trafficking in the vasculature, and CD44 is an important cell
      surface receptor for rolling adhesion. In this study, we demonstrate the
      correlative observation of CD44 distribution at the lymphocyte cell surface in
      liquid by fluorescence optical microscopy and immuno-electron microscopy using an
      atmospheric scanning electron microscope (ASEM). The ultrastructure of the cell
      surface was clearly imaged by ASEM using positively charged Nanogold particles.
      ASEM analysis demonstrated microvilli projections around the cell surface and the
      localization of CD44 on the microvilli. Treatment of cells with cytochalasin D
      resulted in a loss of the microvilli projections and concomitantly abrogated CD44
      mediated adhesion to its ligand hyaluronan. These results suggest the functional
      relevance of microvilli in CD44-mediated rolling adhesion under shear flow. 

PMID- 24135873
TI  - Lipid transport and metabolism in healthy and osteoarthritic cartilage.
AB  - Cartilage is an avascular tissue and cartilage metabolism depends on molecule
      diffusion from synovial fluid and subchondral bone. Thus, nutrient availability
      is limited by matrix permeability according to the size and charge of the
      molecules. Matrix composition limits the access of molecules to chondrocytes,
      determining cell metabolism and cartilage maintenance. Lipids are important
      nutrients in chondrocyte metabolism and are available for these cells through de
      novo synthesis but also through diffusion from surrounding tissues. Cartilage
      status and osteoarthritis development depend on lipid availability. This paper
      reviews lipid transport and metabolism in cartilage. We also analyze signalling
      pathways directly mediated by lipids and those that involve mTOR pathways, both
      in normal and osteoarthritic cartilage. 

PMID- 24135875
TI  - Identification of novel microRNAs in primates by using the synteny information
      and small RNA deep sequencing data.
AB  - Current technologies that are used for genome-wide microRNA (miRNA) prediction
      are mainly based on BLAST tool. They often produce a large number of false
      positives. Here, we describe an effective approach for identifying orthologous
      pre-miRNAs in several primates based on syntenic information. Some of them have
      been validated by small RNA high throughput sequencing data. This approach uses
      the synteny information and experimentally validated miRNAs of human, and
      incorporates currently available algorithms and tools to identify the pre-miRNAs
      in five other primates. First, we identified 929 potential pre-miRNAs in the
      marmoset in which miRNAs have not yet been reported. Then, we predicted the
      miRNAs in other primates, and we successfully re-identified most of the published
      miRNAs and found 721, 979, 650 and 639 new potential pre-miRNAs in chimpanzee,
      gorilla, orangutan and rhesus macaque, respectively. Furthermore, the miRNA
      transcriptome in the four primates have been re-analyzed and some novel predicted
      miRNAs have been supported by the small RNA sequencing data. Finally, we analyzed
      the potential functions of those validated miRNAs and explored the regulatory
      elements and transcription factors of some validated miRNA genes of interest. The
      results show that our approach can effectively identify novel miRNAs and some
      miRNAs that supported by small RNA sequencing data maybe play roles in the
      nervous system. 

PMID- 24135877
TI  - Remarkable improvement in ventricular function after reversion to normal sinus
      rhythm: Cardiac MRI study in a patient with single ventricle s/p Fontan
      procedure.

PMID- 24135878
TI  - Sclerostin as a new key player in arteriovenous fistula calcification.
AB  - BACKGROUND: The osteocyte-derived sclerostin has been shown to play a key
      inhibitor role in determining the normal extent of bone formation, and it
      consequently protects against the deleterious effects of uncontrolled bone
      growth. Sclerostin has been demonstrated to be upregulated during vascular smooth
      muscle cell calcification in vitro and has recently been identified in the human
      aorta at the protein level. Whether the effects of sclerostin on bone turnover
      and its vascular expression also translate into clinically significant changes in
      arteriovenous fistula patency is unknown. PATIENTS AND METHODS: The primary
      outcome was loss of unassisted arteriovenous fistula patency, defined as
      arteriovenous fistula thrombosis or need for intervention. In this prospective
      cohort study, 350 prevalent hemodialysis patients were followed up for 12 months.
      Serum sclerostin levels were measured and arteriovenous fistula calcification was
      detected using a 64-detector computerized tomographic scanner. RESULTS: Patients
      with calcified arteriovenous fistula had higher serum sclerostin levels than
      patients without. Overall, 26 % of the patients reached the outcome during the
      follow-up. The 12-month arteriovenous fistula survival was reduced in patients
      with calcified arteriovenous fistulas. Patients with serum sclerostin levels
      above median levels at the start of the observation period had a worse
      arteriovenous fistula survival. Multivariable-adjusted Cox regression analyses
      revealed that only presence of arteriovenous fistula calcification and serum C
      reactive protein level independently predicted loss of unassisted arteriovenous
      fistula patency. CONCLUSION: Our study suggests that the detection of
      arteriovenous fistula calcification and serum C-reactive protein levels might be
      useful for identifying patients at an increased risk for loss of unassisted
      arteriovenous fistula patency.

PMID- 24135879
TI  - Imaging of vascular tumors with an emphasis on ISSVA classification.
AB  - The International Society for the Study of Vascular Anomalies (ISSVA)
      classification is becoming the international standard classification system for
      vascular tumors and vascular malformations. The ISSVA classification strictly
      distinguishes vascular tumors (neoplastic lesions) from vascular malformations
      (non-neoplastic lesions) based on whether there is a proliferation of vascular
      endothelial cells present, and it is an extremely useful classification system
      for determining therapeutic measures. For vascular tumors, it is clinically
      significant in terms of discriminating infantile hemangioma and rapidly
      involuting congenital hemangioma, which are expected to spontaneously regress,
      from other vascular tumors requiring treatment. Needless to say, clinical courses
      are important for diagnosis, and it is also important for radiologists to
      understand imaging findings on vascular tumors because such tumors have unique
      findings on diagnostic images. In this paper, vascular tumors are classified
      based on the ISSVA classification, and clinical and imaging findings are
      reviewed. 

PMID- 24135880
TI  - Effect of acute administration of L-tyrosine on oxidative stress parameters in
      brain of young rats.
AB  - Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal
      recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic
      tyrosine aminotransferase, and is associated with neurologic and development
      difficulties in numerous patients. Considering that the mechanisms underlying the
      neurological dysfunction in hypertyrosinemic patients are poorly known and that
      studies demonstrated that high concentrations of tyrosine provoke oxidative
      stress in vitro and in vivo in the cerebral cortex of rats, in the present study
      we investigate the oxidative stress parameters (enzymatic antioxidant defenses,
      thiobarbituric acid-reactive substances and protein carbonyl content) in
      cerebellum, hippocampus and striatum of 30-old-day rats after acute
      administration of L-tyrosine. Our results demonstrated that the acute
      administration of L-tyrosine increased the thiobarbituric acid reactive species
      levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and
      striatum. In addition, acute administration of L-tyrosine significantly decreased
      superoxide dismutase activity in cerebellum, hippocampus and striatum, while
      catalase was increased in striatum. In conclusion, the oxidative stress may
      contribute, along with other mechanisms, to the neurological dysfunction
      characteristic of hypertyrosinemia and the administration of antioxidants may be
      considered as a potential adjuvant therapy for tyrosinemia, especially type II. 

PMID- 24135883
TI  - Interprofessional education and practice: a 40-year-old new trend experiencing
      rapid growth.

PMID- 24135882
TI  - Applying bar code medication administration to make a difference in adverse drug
      events with potential for harm: lessons learned.

PMID- 24135881
TI  - Designing DNA interstrand lock for locus-specific methylation detection in a
      nanopore.
AB  - DNA methylation is an important epigenetic regulation of gene transcription.
      Locus-specific DNA methylation can be used as biomarkers in various diseases
      including cancer. Many methods have been developed for genome-wide methylation
      analysis, but molecular diagnotics needs simple tools to determine methylation
      states at individual CpG sites in a gene fragment. In this report, we utilized
      the nanopore single-molecule sensor to investigate a base-pair specific metal
      ion/nucleic acids interaction, and explored its potential application in locus
      specific DNA methylation analysis. We identified that divalent Mercury ion (Hg2+)
      can selectively bind a uracil-thymine mismatch (U-T) in a dsDNA. The Hg2+ binding
      creates a reversible interstrand lock, called MercuLock, which enhances the
      hybridization strength by two orders of magnitude. Such MercuLock cannot be
      formed in a 5-methylcytosine-thymine mismatch (mC-T). By nanopore detection of
      dsDNA stability, single bases of uracil and 5-methylcytosine can be
      distinguished. Since uracil is converted from cytosine by bisulfite treatment,
      cytosine and 5'-methylcytosine can be discriminated. We have demonstrated the
      methylation analysis of multiple CpGs in a p16 gene CpG island. This single
      molecule assay may have potential in detection of epigenetic cancer biomarkers in
      biofluids, with an ultimate goal for early diagnosis of cancer.

PMID- 24135884
TI  - Summer Institute in Nursing Informatics 2013 conference report.

PMID- 24135886
TI  - Bioactive sesquiterpenes from the essential oil of Thuja orientalis.
AB  - A phytochemical investigation on the essential oil of Thuja orientalis resulted
      in the isolation and identification of three new sesquiterpenes, 3alpha-methoxy
      4alpha-epoxythujopsane (1), Delta3,15-4beta-epoxythujopsene (2), and Delta3,4
      thujopsen-2,15-diol (3), together with eight known sesquiterpenoids (4-11). The
      structures of these new compounds were elucidated based on spectroscopic data
      analyses including extensive 2D-NMR data and HR-ESIMS. The full assignments of 1H
      and 13C NMR chemical shifts for thujopsadiene (4) were obtained by 2D-NMR for the
      first time. All compounds (1-11) showed antiproliferative activities against the
      SK-OV-3 and SK-MEL-2 cell lines with IC50 values of 5.85-28.64 uM. In addition,
      compounds 1, 3, 4, 7, 8, and 9 significantly inhibited nitric oxide production in
      lipopolysaccharide-activated BV-2 cells with IC50 values of 3.93-17.85 uM without
      cell toxicity.

PMID- 24135887
TI  - Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple
      drug resistance-associated protein 2 substrate baicalin in rats.
AB  - Baicalin is a major bioactive component of Scutellaria baicalensis and a
      substrate of multiple drug resistance-associated protein 2. Expression of
      multiple drug resistance-associated protein 2 is regulated by NF-E2-related
      factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an
      NF-E2-related factor 2 activator, could influence the oral bioavailability of
      baicalin. A single dose of baicalin (200 mg/kg) was given orally to rats
      pretreated with ursodeoxycholic acid (75 mg/kg and 150 mg/kg, per day,
      intragastrically) or normal saline (per day, intragastrically) for six
      consecutive days. The plasma concentration of baicalin was measured with the HPLC
      method. The result indicated that the oral bioavailability of baicalin was
      significantly and dose-dependently reduced in rats pretreated with
      ursodeoxycholic acid. Compared with control rats, the mean area under
      concentration-time curve of baicalin was reduced from 13.25 +/- 0.24 mg/L h to
      7.62 +/- 0.15 mg/L h and 4.97 +/- 0.21 mg/L h, and the C(max) value was decreased
      from 1.31 +/- 0.03 mg/L to 0.62 +/- 0.05 mg/L and 0.36 +/- 0.04 mg/L in rats
      pretreated with ursodeoxycholic acid at doses of 75 mg/kg and 150 mg/kg,
      respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment
      reduced the oral bioavailability of baicalin in rats, probably due to the
      enhanced efflux of baicalin from the intestine and liver by multiple drug
      resistance-associated protein 2.

PMID- 24135889
TI  - Sleep and its relationship to pain, dysfunction, and disease activity in juvenile
      idiopathic arthritis.
AB  - The objective of this study was to determine the sleep abnormalities that may
      exist in Moroccan children with juvenile idiopathic arthritis (JIA) and their
      relationship to pain, dysfunction, and disease activity. Case control study
      including 47 patients diagnosed with JIA, according to the criteria of the
      International League of Associations for Rheumatology (ILAR), and 47 healthy
      children, age and sex matched. Sleep was assessed by Children's Sleep Habits
      Questionnaire (CSHQ). All parents have filled the 45 items of the CSHQ and
      grouped into eight subscales: bedtime resistance, sleep onset delay, sleep
      duration, sleep anxiety, sleep-disordered breathing, night awakenings,
      parasomnias, and morning awakening/daytime sleepiness. The disease activity was
      assessed by the number of painful joints, swelling joints, erythrocyte
      sedimentation rate, c-protein reactive, and Juvenile Arthritis Disease Activity
      Score (JADAS). Functional assessment was based on the value of Childhood Health
      Assessment Questionnaire. Pain was assessed by visual analog scale pain. Forty
      seven patients were included, with 28 males (59.6 %). Children with JIA had a
      total score of CSHQ significantly higher than the control cases (p < 0.0001);
      significant differences were also found in the subscale sleep onset delay, sleep
      anxiety, sleep-disordered breathing, night awakenings, and parasomnias with a p
      value of <0.0001, 0.034, <0.0001, 0.001, and 0.00, respectively. Significant
      association was found between the CSHQ total score and visual analog scale (VAS)
      physician activity (p = 0.016) and JADAS (p = 0.05). There was a correlation
      between the sleep-disordered breathing and JADAS (p = 0.04). Sleep onset delay
      was associated with VAS patient pain (p = 0.05), as nocturnal awakenings and VAS
      patient pain (p = 0.016). Finally, parasomnias and physician's VAS activity (p =
      0.015) and VAS patient pain (p = 0.03) were also correlated. This study suggests
      that sleep abnormalities are common in children with JIA. Strategies to improve
      sleep should be studied as a possible tool of improving the quality of life of
      children with rheumatic disease. 

PMID- 24135891
TI  - High current density via direct electron transfer by the halophilic anode
      respiring bacterium Geoalkalibacter subterraneus.
AB  - In this study the characterization of Geoalkalibacter subterraneus is presented,
      which is a novel halophilic anode respiring bacterium (ARB) previously selected
      and identified in a potentiostatically controlled bioelectrochemical system (BES)
      inoculated with sediments from a salt plant. Pure culture electroactive biofilms
      of Glk. subterraneus were grown during chronoamperometric batch experiments at a
      graphite electrode poised at +200 mV (vs. SCE) with 10 mM acetate as the electron
      donor. These biofilms exhibited the highest current density (4.68 +/- 0.54 A m(
      2)) reported on a planar material with a pure culture under saline conditions
      (3.5% NaCl). To investigate possible anodic electron transfer (ET) mechanisms,
      cyclic voltammetry (CV) of mature visible apparent reddish biofilms was performed
      under bioelectrocatalytic substrate consumption (turnover) and in the absence of
      the substrate (non-turnover). CV evidenced a well defined typical sigmoidal shape
      and a pair of clear redox couples under turnover and non-turnover conditions,
      respectively. Moreover, the calculation of their formal potentials indicated the
      presence of a common ET mechanism present in both CV conditions between -427.6 +/
      0.5 (Ef,2) and -364.8 +/- 4.5 mV (Ef,3). Confocal laser scanning microscopy
      inspection showed a biofilm structure composed of several layers of metabolically
      active bacteria that spread all over the electrode material within a biofilm up
      to 76 +/- 7 MUm thick. Such high value compared to the thickness values normally
      reported in the literature for pure culture electroactive bacteria justifies
      further investigations. Taken together, these results suggest that Glk.
      subterraneus performs a direct ET mechanism in contact with the electrode
      material. Furthermore, direct current generation from saline wastewater
      significantly expands the application of BESs. 

PMID- 24135890
TI  - Modifiable cardiovascular risk factors in patients with ankylosing spondylitis.
AB  - The aim of this study was to evaluate whether modifiable cardiovascular disease
      (CVD) risk factors, e.g. atherogenic blood lipids, hypertension and lifestyle
      related factors such as smoking, diet and physical inactivity, differ among
      patients with ankylosing spondylitis (AS) in comparison to the general
      population. Eighty-eight patients diagnosed with AS were identified by analysis
      of the databases of a previous community intervention programme, the Vasterbotten
      intervention programme. The patients were compared with 351 controls matched for
      age, sex and study period. These databases include the results of blood samples
      analysed for cholesterol, triglycerides and plasma glucose, as well as data on
      hypertension, height, weight, smoking and dietary habits and physical activity.
      No significant differences were found between patients and controls regarding
      hypertension, body mass index, physical activity, diet or smoking. Levels of
      serum triglycerides (p < 0.01) and cholesterol (p < 0.01) were significantly
      lower in the patient group. Among the patients, the level of triglycerides
      correlated inversely with the intake of total fat (r s = -0.25, p < 0.05),
      monounsaturated fats (r s = -0.29, p < 0.05) and positively correlated to the
      intake of carbohydrates (r s = 0.26, p < 0.05). These associations were not
      apparent among the controls. In the cohort of AS patients studied, no differences
      were found regarding the modifiable risk factors for CVD compared with the
      general population. Hence, the increased presence of CVD in patients with AS may
      be caused by other factors such as differences in metabolism and medication such
      as NSAID or the chronic low-grade inflammation present in the disease. 

PMID- 24135892
TI  - Diagnostic accuracy and patient acceptance of MRI in children with suspected
      appendicitis.
AB  - OBJECTIVE: To compare magnetic resonance imaging (MRI) and ultrasound in children
      with suspected appendicitis. METHODS: In a single-centre diagnostic accuracy
      study, children with suspected appendicitis were prospectively identified at the
      emergency department. All underwent abdominal ultrasound and MRI within 2 h, with
      the reader blinded to other imaging findings. An expert panel established the
      final diagnosis after 3 months. We evaluated the diagnostic accuracy of three
      imaging strategies: ultrasound only, conditional MRI after negative or
      inconclusive ultrasound, and MRI only. Significance between sensitivity and
      specificity was calculated using McNemar's test statistic. RESULTS: Between April
      and December 2009 we included 104 consecutive children (47 male, mean age 12).
      According to the expert panel, 58 patients had appendicitis. The sensitivity of
      MRI only and conditional MRI was 100% (95% confidence interval 92-100), that of
      ultrasound was significantly lower (76%; 63-85, P < 0.001). Specificity was
      comparable among the three investigated strategies; ultrasound only 89% (77-95),
      conditional MRI 80% (67-89), MRI only 89% (77-95) (P values 0.13, 0.13 and 1.00).
      CONCLUSION: In children with suspected appendicitis, strategies with MRI (MRI
      only, conditional MRI) had a higher sensitivity for appendicitis compared with a
      strategy with ultrasound only, while specificity was comparable. KEY POINTS: * In
      children, MRI has a higher sensitivity for appendicitis than ultrasound. *
      Ultrasound followed by MRI in negative or inconclusive findings is accurate. *
      The tolerance for ultrasound and MRI in children is comparable. * MRI can be
      performed in children in an emergency setting.

PMID- 24135893
TI  - Roflumilast for the treatment of COPD in an Asian population: a randomized,
      double-blind, parallel-group study.
AB  - BACKGROUND: Roflumilast is the only oral phosphodiesterase 4 inhibitor indicated
      for use in the treatment of COPD. Previous studies of roflumilast have
      predominantly involved European and North American populations. A large study was
      necessary to determine the efficacy and safety of roflumilast in a predominantly
      ethnic Chinese population. METHODS: In a placebo-controlled, double-blind,
      parallel-group, multicenter, phase 3 study, patients of Chinese, Malay, and
      Indian ethnicity (N = 626) with severe to very severe COPD were randomized 1:1 to
      receive either roflumilast 500 MUg once daily or placebo for 24 weeks. The
      primary end point was change in prebronchodilator FEV1 from baseline to study
      end. RESULTS: Three hundred thirteen patients were assigned to each treatment.
      Roflumilast provided a sustained increase over placebo in mean prebronchodilator
      FEV1 (0.071 L; 95% CI, 0.046, 0.095 L; P < .0001). Similar improvements were
      observed in the secondary end points of postbronchodilator FEV1 (0.068 L; 95% CI
      0.044, 0.092 L; P < .0001) and prebronchodilator and postbronchodilator FVC
      (0.109 L; 95% CI, 0.061, 0.157 L; P < .0001 and 0.101 L; 95% CI, 0.055, 0.146 L;
      P < .0001, respectively). The adverse event profile was consistent with previous
      roflumilast studies. The most frequently reported treatment-related adverse event
      was diarrhea (6.0% and 1.0% of patients in the roflumilast and placebo groups,
      respectively). CONCLUSIONS: Roflumilast plays an important role in lung function
      improvement and is well tolerated in an Asian population. It provides an optimal
      treatment choice for patients with severe to very severe COPD.

PMID- 24135894
TI  - Effect of avocado soybean unsaponifiables on insulin secretion and insulin
      sensitivity in patients with obesity.
AB  - AIM: To evaluate the effect of avocado soybean unsaponifiables (ASU) on insulin
      secretion and insulin sensitivity in patients with obesity. METHODS: A
      randomized, double-blind, placebo-controlled, clinical trial was carried out in
      14 obese adult volunteers. After random allocation of the intervention, 7
      patients received 300 mg of ASU or placebo during a fasting state for 3 months. A
      metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP)
      levels was carried out prior to the intervention. A hyperglycemic
      hyperinsulinemic clamp technique was used to assess insulin secretion and insulin
      sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for
      statistical analyses. The study was approved by the local ethics committee of our
      institution. RESULTS: At baseline, both groups were similar according to clinical
      and laboratory characteristics. There was no significant difference in insulin
      secretion and insulin sensitivity with ASU. CONCLUSIONS: ASU administration for 3
      months did not modify insulin secretion and insulin sensitivity in patients with
      obesity.

PMID- 24135895
TI  - Cu(II)-catalyzed highly regio- and stereoselective construction of C-C double
      bonds: an efficient method for the ketonization-olefination of indoles.
AB  - A general and efficient method for the cross-coupling of indoles with beta-keto
      esters by using TEMPO/CuSO4.5H2O in air as oxidant has been developed. This
      reaction features high functional-group compatibility and an excellent
      selectivity. This methodology provides an alternative approach for the
      ketonization-olefination of indoles in moderate to good yields. 

PMID- 24135896
TI  - A photoactivatable drug-caged fluorophore conjugate allows direct quantification
      of intracellular drug transport.
AB  - We report here a method that utilizes a photoactivatable drug-caged fluorophore
      conjugate to quantify intracellular drug trafficking processes at single cell
      resolution. Photoactivation is performed in labeled cellular compartments to
      visualize intracellular drug exchange under physiological conditions, without the
      need for washing, facilitating its translation into in vivo cancer models. 

PMID- 24135897
TI  - Distinct functions of Ulk1 and Ulk2 in the regulation of lipid metabolism in
      adipocytes.
AB  - ULK1 (unc-51 like kinase 1) is a serine/threonine protein kinase that plays a key
      role in regulating the induction of autophagy. Recent studies using autophagy
      defective mouse models, such as atg5- or atg7-deficient mice, revealed an
      important function of autophagy in adipocyte differentiation. Suppression of
      adipogenesis in autophagy-defective conditions has made it difficult to study the
      roles of autophagy in metabolism of differentiated adipocytes. In this study, we
      established autophagy defective-differentiated 3T3-L1 adipocytes, and
      investigated the roles of Ulk1 and its close homolog Ulk2 in lipid and glucose
      metabolism using the established adipocytes. Through knockdown approaches, we
      determined that Ulk1 and Ulk2 are important for basal and MTORC1 inhibition
      induced autophagy, basal lipolysis, and mitochondrial respiration. However,
      unlike other autophagy genes (Atg5, Atg13, Rb1cc1/Fip200, and Becn1) Ulk1 was
      dispensable for adipogenesis without affecting the expression of CCAAT/enhancer
      binding protein ? (CEBPA) and peroxisome proliferation-activated receptor gamma
      (PPARG). Ulk1 knockdown reduced fatty acid oxidation and enhanced fatty acid
      uptake, the metabolic changes that could contribute to adipogenesis, whereas Ulk2
      knockdown had opposing effects. We also found that the expression levels of
      insulin receptor (INSR), insulin receptor substrate 1 (IRS1), and glucose
      transporter 4 (SLC2A4/GLUT4) were increased in Ulk1-silenced adipocytes, which
      was accompanied by upregulation of insulin-stimulated glucose uptake. These
      results suggest that ULK1, albeit its important autophagic role, regulates lipid
      metabolism and glucose uptake in adipocytes distinctly from other autophagy
      proteins. 

PMID- 24135898
TI  - Ground water contamination with (238)U, (234)U, (235)U, (226)Ra and (210)Pb from
      past uranium mining: cove wash, Arizona.
AB  - The objectives of the study are to present a critical review of the (238)U,
      (234)U, (235)U, (226)Ra and (210)Pb levels in water samples from the EPA studies
      (U.S. EPA in Abandoned uranium mines and the Navajo Nation: Red Valley chapter
      screening assessment report. Region 9 Superfund Program, San Francisco, 2004,
      Abandoned uranium mines and the Navajo Nation: Northern aum region screening
      assessment report. Region 9 Superfund Program, San Francisco, 2006, Health and
      environmental impacts of uranium contamination, 5-year plan. Region 9 Superfund
      Program, San Franciso, 2008) and the dose assessment for the population due to
      ingestion of water containing (238)U and (234)U. The water quality data were
      taken from Sect. "Data analysis" of the published report, titled Abandoned
      Uranium Mines Project Arizona, New Mexico, Utah-Navajo Lands 1994-2000, Project
      Atlas. Total uranium concentration was above the maximum concentration level for
      drinking water (7.410-1 Bq/L) in 19 % of the water samples, while (238)U and
      (234)U concentrations were above in 14 and 17 % of the water samples,
      respectively. (226)Ra and (210)Pb concentrations in water samples were in the
      range of 3.7 * 10(-1) to 5.55 * 102 Bq/L and 1.11 to 4.33 * 102 Bq/L,
      respectively. For only two samples, the (226)Ra concentrations exceeded the MCL
      for total Ra for drinking water (0.185 Bq/L). However, the (210)Pb/(226)Ra ratios
      varied from 0.11 to 47.00, and ratios above 1.00 were observed in 71 % of the
      samples. Secular equilibrium of the natural uranium series was not observed in
      the data record for most of the water samples. Moreover, the (235)U/(total)U mass
      ratios ranged from 0.06 to 5.9 %, and the natural mass ratio of (235)U to
      (total)U (0.72 %) was observed in only 16 % of the water samples, ratios above or
      below the natural ratio could not be explained based on data reported by U.S.
      EPA. In addition, statistical evaluations showed no correlations among the
      distribution of the radionuclide concentrations in the majority of the water
      samples, indicating more than one source of contamination could contribute to the
      sampled sources. The effective doses due to ingestion of the minimum uranium
      concentrations in water samples exceed the average dose considering inhalation
      and ingestion of regular diet for other populations around the world (1
      MUSv/year). The maximum doses due to ingestion of (238)U or (234)U were above the
      international limit for effective dose for members of the public (1 mSv/year),
      except for inhabitants of two chapters. The highest effective dose was estimated
      for inhabitants of Cove, and it was almost 20 times the international limit for
      members of the public. These results indicate that ingestion of water from some
      of the sampled sources poses health risks.

PMID- 24135899
TI  - T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor
      therapy.
AB  - Oncolytic vaccinia virus (VV) therapy has shown promise in preclinical models and
      in clinical studies. However, complete responses have rarely been observed. This
      lack of efficacy is most likely due to suboptimal virus spread through the tumor
      resulting in limited tumor cell destruction. We reasoned that redirecting T cells
      to the tumor has the potential to improve the antitumor activity of oncolytic
      VVs. We, therefore, constructed a VV encoding a secretory bispecific T-cell
      engager consisting of two single- chain variable fragments specific for CD3 and
      the tumor cell surface antigen EphA2 (EphA2-T-cell engager-armed VV (EphA2-TEA
      VV)). In vitro, EphA2-TEA-VV's ability to replicate and induce oncolysis was
      similar to that of unmodified virus. However, only tumor cells infected with
      EphA2-TEA-VV induced T-cell activation as judged by the secretion of interferon
      gamma and interleukin-2. In coculture assays, EphA2-TEA-VV not only killed
      infected tumor cells, but in the presence of T cells, it also induced bystander
      killing of noninfected tumor cells. In vivo, EphA2-TEA-VV plus T cells had potent
      antitumor activity in comparison with control VV plus T cells in a lung cancer
      xenograft model. Thus, arming oncolytic VVs with T-cell engagers may represent a
      promising approach to improve oncolytic virus therapy. 

PMID- 24135901
TI  - Development of the KnowPain-12 pain management knowledge survey.
AB  - OBJECTIVE: The purpose of this study was to develop a brief knowledge survey
      about chronic noncancer pain that could be used as a reliable and valid measure
      of a provider's pain management knowledge. METHODS: This study used a cross
      sectional study design. A group of pain experts used a systematic consensus
      approach to reduce the previously validated KnowPain-50 to 12 questions (2 items
      per original 6 domains). A purposive sampling of pain specialists and health
      professionals generated from public lists and pain societies was invited to
      complete the KnowPain-12 online survey. Between April 4 and September 16, 2012,
      846 respondents completed the survey. RESULTS: Respondents included registered
      nurses (34%), physicians (23%), advanced practice registered nurses (14%), and
      other allied health professionals and students. Twenty-six percent of the total
      sample self-identified as "pain specialist." Pain specialists selected the most
      correct response to the knowledge assessment items more often than did those who
      did not identify as pain specialists, with the exception of 1 item. KnowPain-12
      demonstrated adequate internal consistency reliability (alpha=0.67). Total scores
      across all 12 items were significantly higher (P<0.0001) among pain specialists
      compared with respondents who did not self-identify as pain specialists.
      DISCUSSION: The psychometric properties of the KnowPain-12 support its potential
      as an instrument for measuring provider pain management knowledge. The ability to
      assess pain management knowledge with a brief measure will be useful for
      developing future research studies and specific pain management knowledge
      intervention approaches for health care providers.

PMID- 24135900
TI  - Phenotype matters: the absence of a positive association between cortical
      thinning and chronic low back pain when controlling for salient clinical
      variables.
AB  - AIMS/OBJECTIVES/BACKGROUND: Studies have associated chronic low back pain (cLBP)
      with grey matter thinning. But these studies have not controlled for important
      clinical variables (such as a comorbid affective disorder, pain medication, age,
      or pain phenotype), which may reduce or eliminate these associations. METHODS: We
      conducted cortical thickness and voxel-based morphometry (VBM) analyses in 14
      cLBP patients with a discogenic component to their pain, not taking opioids or
      benzodiazepines, and not depressed or anxious. They were age and gender matched
      to 14 pain-free controls (PFCs). An ROI-driven analysis (regions of interest) was
      conducted, using 18 clusters from a previous arterial spin labeling study
      demonstrating greater regional cerebral blood flow (rCBF) in these cLBP subjects
      than the PFCs. Cortical thickness and VBM-based gray matter volume measurements
      were obtained from a structural MRI scan and group contrasts were calculated.
      RESULTS: Multivariate analysis of variance showed a trend toward cortical
      thickening in the right paracentral lobule in cLBP subjects (F1,17=3.667,
      P<0.067), and significant thickening in the right rostral middle frontal gyrus
      (F1,17=6.880, P<0.014). These clusters were non-significant after including age
      as a covariate (P<0.891; P<0.279). A whole-brain cortical thickness and VBM
      analysis also did not identify significant clusters of thinning or thickening.
      Exploratory analyses identified group differences for correlations between age
      and cortical thickness of the right rostral middle frontal gyrus (cLBP: R=-0.03,
      P=0.9; PFCs: R=-0.81, P<0.001), that is, PFCs demonstrated age-related thinning
      while cLBP patients did not. CONCLUSIONS: Our pilot results suggest that
      controlling for affect, age, and concurrent medications may reduce or eliminate
      some of the previously reported structural brain alterations in cLBP.

PMID- 24135902
TI  - Convergent validity evidence for the Pain and Discomfort Scale (PADS) for pain
      assessment among adults with intellectual disability.
AB  - OBJECTIVES: The main aim of the study was to generate initial convergent validity
      evidence for the Pain and Discomfort Scale (PADS) for use with nonverbal adults
      with intellectual disabilities. MATERIALS AND METHODS: Forty-four adults with
      intellectual disability (mean age=46, 52% male) were evaluated using a
      standardized sham-controlled and blinded sensory testing protocol, from which
      Facial Action Coding System (FACS) and PADS scores were tested for (1)
      sensitivity to an array of calibrated sensory stimuli; (2) specificity (active
      vs. sham trials); and (3) concordance. RESULTS: The primary findings were those
      participants who were reliably coded using both FACS and PADS approaches as being
      reactive to the sensory stimuli (FACS: F(2,86)=4.71, P<0.05, PADS: F(2,86)=21.49,
      P<0.05) (sensitivity evidence), not reactive during the sham stimulus trials
      (FACS: F(1,43)=3.77, P=0.06, PADS: F(1,43)=5.87, P=0.02) (specificity evidence),
      and there were significant (r=0.41 to 0.51, P<0.01) correlations between PADS and
      FACS (convergent validity evidence). DISCUSSION: FACS is an objective coding
      platform for facial expression. It requires intensive training and resources for
      scoring. As such it may be limited for clinical application. PADS was designed
      for clinical application. PADS scores were comparable with FACS scores under
      controlled evaluation conditions providing partial convergent validity evidence
      for its use.

PMID- 24135903
TI  - Relationships between psychological factors, pain, and disability in complex
      regional pain syndrome and low back pain.
AB  - OBJECTIVE: Cognitive and emotional factors are known to influence peoples' pain
      experiences in many conditions, including low back pain. However, in complex
      regional pain syndrome (CRPS), their role is unclear. This study aimed to assess
      the relationships between psychological factors, pain, and disability in CRPS,
      compared with low back pain. This could help to identify target variables for
      psychological treatment. MATERIALS AND METHODS: A total of 88 CRPS patients and
      88 low back pain patients completed measures of pain, disability, depression,
      anxiety, and fear of movement and reinjury (kinesiophobia). Mean scores between
      the 2 groups were compared, and correlations between psychological factors, pain,
      and disability were compared between the 2 groups. Predictors of pain and
      disability were assessed using multiple regression analyses. RESULTS: The 2
      groups had remarkably similar scores on measures of pain, disability, depression,
      anxiety, and kinesiophobia. In both groups, those who were more depressed,
      anxious, and kinesiophobic were more disabled. For the CRPS group (but not the
      low back pain group), pain intensity significantly correlated with distress.
      Multivariate analyses showed that the unique predictors of disability for the 2
      groups were pain and depression, and that depression had a stronger relationship
      with disability for the CRPS group. For both groups, pain intensity was predicted
      by kinesiophobia, and anxiety was a unique predictor in the CRPS group only.
      DISCUSSION: In CRPS, disability and pain severity were more strongly associated
      with psychological factors than they were in low back pain. Cause and effect
      relationships could not be established by this cross-sectional study.

PMID- 24135904
TI  - Nystagmus-based approach to vertebrobasilar stroke presenting as vertigo without
      initial neurologic signs.
AB  - BACKGROUND: We aimed to investigate the clinical courses and common nystagmus of
      isolated vertigo patients with vertebrobasilar stroke. METHODS: The patients who
      presented with isolated acute spontaneous vertigo with spontaneous nystagmus
      (acute vestibular syndrome) at the Emergency Department were retrospectively
      analyzed. They were referred to the Otolaryngology Department due to the absence
      of neurologic signs or even of imaging abnormalities after the initial
      examination at the Emergency Department. Various clinical features, including
      presenting symptoms, delayed neurologic signs, the site of infarction, and
      videonystagmographic (VNG) findings were analyzed. RESULTS: Of the 468 cases of
      acute vestibular syndrome, 23 (4.9%) cases of radiologically proven
      vertebrobasilar stroke were identified. Of the 23 patients, 17 (74%) showed
      aggravation of vertigo or delayed neurologic signs during the admission. In the
      analysis of VNG, 11 (48%) cases of direction-changing gaze-evoked nystagmus, 7
      (30%) cases of fixation failure in the caloric test, 6 (27%) cases of periodic
      alternating nystagmus, and 4 (17%) cases of atypical head-shaking nystagmus were
      presented. Stroke occurred in the cerebellum (n=18, 78%), medulla (n=4, 17%), and
      pons (n=1, 4%). CONCLUSION: In the early stage of vertebrobasilar stroke, an
      accurate diagnosis was difficult in the Emergency Department even though a
      radiologic study was performed, but various VNG abnormalities and delayed
      neurologic signs could help to diagnose whether the origin is central or not.

PMID- 24135905
TI  - [Cutaneous melanoma - "black death" of modern times? Traces in contemporary
      literature].
AB  - Cutaneous melanoma, sometimes labeled as "black skin cancer", is increasing in
      frequency and becoming a more common literary motive. In US literature, Sylvia
      Plath and Charles Bukowski depicted melanoma more than 50 years ago, later
      Stephen King and Thomas C. Boyle. In German literature, Charlotte Roche shortly
      mentioned this tumor. Jorg Ponnighaus, both poet and dermatologist, intensively
      deals in his poems with the effects melanoma has on patients and doctors alike.
      Melanoma definitely is not the "Black Death" of modern times. However, the
      perception of this tumor as extremely malignant and as life-threatening makes
      melanoma a metaphor of the deadly danger of cancer. 

PMID- 24135906
TI  - Infection of prions and treatment of PrP106-126 alter the endogenous status of
      protein 14-3-3 and trigger the mitochondrial apoptosis possibly via activating
      Bax pathway.
AB  - The 14-3-3 proteins are a family of highly homologous and ubiquitously expressed
      isoforms that are involved in a wide variety of physiological processes. 14-3-3
      have showed actively molecular interaction with PrP and positive 14-3-3 is
      frequently observed in the cerebrospinal fluid (CSF) samples of the patients with
      sporadic Creutzfeldt-Jakob disease (CJD). However, the alterations of 14-3-3 in
      the brain tissues of patients with prion diseases remain little addressed. To
      address the possible change of brain 14-3-3 during prion infection, we firstly
      tested the levels of 14-3-3 in the brain tissues of scrapie agent 263 K infected
      hamsters. Obviously decreased 14-3-3 were observed in the samples of the infected
      animals, showing time-dependent reduction in the incubation period, while the
      amounts of S-nitrosylated 14-3-3 were increased in the brains collected at the
      late stage. A low level of 14-3-3 was also observed in the scrapie infectious
      cell line SMB-S15, accompanied with up-regulated Bax and down-regulated Bcl-2.
      Moreover, we found that treatment of PrP106-126 on the cultured cells decreased
      the cellular 14-3-3 and caused translocations of cellular Bax to the membrane
      fractions. Knockdown of cellular 14-3-3 sensitized the cultured cells to the
      challenge of PrP106-126. These data illustrate that significant down-regulation
      of brain 14-3-3 levels during prion infection may not only be a scenario of the
      terminal consequence of interacting with abnormal PrP(Sc) but may also
      participate in the pathogenesis of neuronal damage.

PMID- 24135907
TI  - Expression stability of reference genes for quantitative RT-PCR of healthy and
      diseased pituitary tissue samples varies between humans, mice, and dogs.
AB  - Pituitary surgery generates pituitary tissue for histology, immunohistochemistry,
      and molecular biological research. In the last decade, the pathogenesis of
      pituitary adenomas has been extensively studied in humans, and to a lesser degree
      in dogs, and tumor oncogenesis has been studied in knock-out mice, often by means
      of quantitative reversed-transcriptase PCR (RT-qPCR). A precondition of such
      analyses is that so-called reference genes are stably expressed regardless of
      changes in disease status or treatment. In this study, the expression of six
      frequently used reference genes, namely, tata box binding protein (tbp), tyrosine
      3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide
      (ywhaz), hydroxymethylbilane synthase (hmbs), beta-2-microglobulin (b2m),
      succinate dehydrogenase complex subunit A (sdha), and glyceraldehyde 3 phosphate
      dehydrogenase 1 (gapdh), was studied in pituitary tissue (normal and adenoma)
      from three species (humans, mice, and dogs). The stability of expression of these
      reference genes differed between species and between healthy and diseased tissue
      within one species. Quantitative analysis based on a single reference gene that
      is assumed to be stably expressed might lead to wrong conclusions. This cross
      species analysis clearly emphasizes the need to evaluate the expression stability
      of reference genes as a standard and integral aspect of study design and data
      analysis, in order to improve the validity of the conclusions drawn on the basis
      of quantitative molecular analyses. 

PMID- 24135908
TI  - Genomics meets proteomics: identifying the culprits in disease.
AB  - Genome-wide association studies (GWAS) revealed genomic risk loci that
      potentially have an impact on disease and phenotypic traits. This extensive
      resource holds great promise in providing novel directions for personalized
      medicine, including disease risk prediction, prevention and targeted medication.
      One of the major challenges that researchers face on the path between the initial
      identification of an association and precision treatment of patients is the
      comprehension of the biological mechanisms that underlie these associations.
      Currently, the focus to solve these questions lies on the integrative analysis of
      system-wide data on global genome variation, gene expression, transcription
      factor binding, epigenetic profiles and chromatin conformation. The generation of
      this data mainly relies on next-generation sequencing. However, due to multiple
      recent developments, mass spectrometry-based proteomics now offers additional, by
      the GWAS field so far hardly recognized possibilities for the identification of
      functional genome variants and, in particular, for the identification and
      characterization of (differentially) bound protein complexes as well as
      physiological target genes. In this review, we introduce these proteomics
      advances and suggest how they might be integrated in post-GWAS workflows. We
      argue that the combination of highly complementary techniques is powerful and can
      provide an unbiased, detailed picture of GWAS loci and their mechanistic
      involvement in disease. 

PMID- 24135909
TI  - Antibiotic stewardship in Germany: a cross-sectional questionnaire survey of 355
      intensive care units.
AB  - PURPOSE: Little information is available on antibiotic prescription management in
      German hospitals. The objective of this cross-sectional study was to determine
      the prevalence and components of antibiotic stewardship measures in German
      intensive care units (ICUs). METHODS: A questionnaire survey was sent to all ICUs
      participating in the German nosocomial infection surveillance system (n = 579) in
      October 2011. Data on antibiotic management structures were collected and
      analyzed by structural hospital and ICU factors. RESULTS: The questionnaire was
      completed by 355 German ICUs (response rate 61 %). Common measures used (>80 % of
      the ICUs) were personnel restrictions for antibiotic prescriptions, routine
      access to bacterial resistance data, and pharmacy reports on antibiotic costs and
      consumption. A small proportion of ICUs (14 %) employed physicians specialized in
      the prescription of antimicrobial medication. Hospitals with their own
      microbiological laboratory report participation in surveillance networks for
      antimicrobial use (34 %) and bacterial resistance (32 %) twice as often as
      hospitals with external laboratories (15 and 14 %, respectively, p < 0.001).
      Also, non-profit and public hospitals participate more often in surveillance
      networks for bacterial resistance than private hospitals (>23 % vs. 11 %, p <
      0.05). CONCLUSIONS: While the majority of ICUs report to have some antibiotic
      policies established, the contents and composition of these policies vary.
      Organizational-level control strategies to improve antibiotic management are
      common in Germany. However, strategies widely considered effective, such as the
      systematic cross-institutional surveillance of antimicrobial use and bacterial
      resistance in a standardized manner or the employment of infectious disease
      specialists, are scarce. This study provides a benchmark for future antibiotic
      stewardship programs.

PMID- 24135910
TI  - Shrimp lipids: a source of cancer chemopreventive compounds.
AB  - Shrimp is one of the most popular seafoods worldwide, and its lipids have been
      studied for biological activity in both, muscle and exoskeleton. Free fatty
      acids, triglycerides, carotenoids, and other lipids integrate this fraction, and
      some of these compounds have been reported with cancer chemopreventive
      activities. Carotenoids and polyunsaturated fatty acids have been extensively
      studied for chemopreventive properties, in both in vivo and in vitro studies.
      Their mechanisms of action depend on the lipid chemical structure and include
      antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory
      activities, among others. The purpose of this review is to lay groundwork for
      future research about the properties of the lipid fraction of shrimp. 

PMID- 24135913
TI  - The coordination chemistry of tartronic acid with copper: magnetic studies of a
      quasi-equilateral tricopper triangle.
AB  - The coordination chemistry of tartronic acid, , with copper(ii) has been
      investigated. Structures of two complexes are reported containing respectively
      the complex [Cu(-2H)2Cl](3-) where acts as a bidentate ligand through
      carboxylates, and [Cu3(-3H)3](3-) where the alcohol function is deprotonated to
      bridge two coppers in a triangular trinuclear complex. The latter species
      undergoes facile oxidation leading to carbon-carbon bond formation. The magnetic
      and EPR properties of the trinuclear complex have been studied in detail. 

PMID- 24135912
TI  - Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in
      articular chondrocytes of mouse models of OA.
AB  - The goal of this study is to determine whether transforming growth factor beta 1
      (Tgf-beta1) induces the high temperature requirement A1 (HtrA1) in articular
      chondrocytes of two mouse models of osteoarthritis (OA). Early onset articular
      cartilage degeneration in the mouse models was characterized by histology.
      Expression profiles of Tgf-beta1, p-Smad1, p-Smad2/3 and HtrA1 in knee joints of
      the mouse models were examined by immunofluorescene. By in vitro and ex vivo
      experiments, human primary chondrocytes and articular cartilages from femoral
      condyles of mice were treated with recombinant human TGF-beta1 and an ALK5
      chemical inhibitor, SB431542. The level of HTRA1 mRNA in human and mouse
      articular chondrocytes was examined by real-time PCR. Chondrocyte clusters were
      present in the articular cartilage of knee joints in the mouse models. Increased
      expressions of Tgf-beta1, p-Smad2/3 and HtrA1 were detected in the articular
      chondrocyte of knee joints in the mouse models. The increased expressions of p
      Smad2/3 and HtrA1 were co-localized in the articular chondrocyte of the knee
      joints. The expression of p-Smad1 was hardly detectable in the mouse models and
      their corresponding wild-type littermates. The level of HTRA1 mRNA was increased
      in human and mouse articular chondrocytes treated with TGF-beta1, compared with
      that in chondrocytes without the treatment of TGF-beta1. The TGF-beta1-induced
      expression of HTRA1 in human and mouse articular chondrocytes was inhibited by
      SB431542. These results suggest that the Tgf-beta1 canonical signaling was
      activated to induce HtrA1 in the articular chondrocytes of the mouse models of
      OA.

PMID- 24135911
TI  - Reporter dyes demonstrate functional expression of multidrug resistance proteins
      in the marine flatworm Macrostomum lignano: the sponge-derived dye Ageladine A is
      not a substrate of these transporters.
AB  - The marine plathyhelminth Macrostomum lignano was recently isolated from Adriatic
      shore sediments where it experiences a wide variety of environmental challenges,
      ranging from hypoxia and reoxygenation, feeding on toxic algae, to exposure to
      anthropogenic contaminants. As multidrug resistance transporters constitute the
      first line of defense against toxins and toxicants we have studied the presence
      of such transporters in M. lignano in living animals by applying optical methods
      and pharmacological inhibitors that had been developed for mammalian cells.
      Application of the MDR1 inhibitor Verapamil or of the MRP1 inhibitors MK571 or
      Probenecid increased the intracellular fluorescence of the reporter dyes Fura-2
      am, Calcein am, Fluo-3 am in the worms, but did not affect their staining with
      the dyes Rhodamine B, CMFDA or Ageladine A. The marine sponge alkaloid Ageladine
      A remained intracellularly trapped for several days in the worms, suggesting that
      it does not serve as substrate of multidrug resistance exporters. In addition,
      Ageladine A did not affect multidrug resistance-associated protein (MRP)-mediated
      dye export from M. lignano or the MRP1-mediated glutathione (GSH) export from
      cultured rat brain astrocytes. The data obtained demonstrate that life-imaging is
      a useful tool to address physiological drug export from intact marine transparent
      flatworms by using multiphoton scanning microscopy. 

PMID- 24135914
TI  - Viking and early Middle Ages northern Scandinavian textiles proven to be made
      with hemp.
AB  - Nowadays most plant textiles used for clothing and household are made of cotton
      and viscose. Before the 19th century however, plant textiles were mainly made
      from locally available raw materials, in Scandinavia these were: nettle, hemp and
      flax. It is generally believed that in Viking and early Middle Ages Scandinavia
      hemp was used only for coarse textiles (i.e. rope and sailcloth). Here we present
      an investigation of 10 Scandinavian plant fibre textiles from the Viking and
      Early Middle Ages, believed to be locally produced. Up till now they were all
      believed to be made of flax. We show that 4 textiles, including two pieces of the
      famous Overhogdal Viking wall-hanging are in fact made with hemp (in three cases
      hemp and flax are mixed). This indicates that hemp was important, not only for
      coarse but also for fine textile production in Viking and Early Middle Ages in
      Scandinavia. 

PMID- 24135915
TI  - Efficacy and tolerability of solifenacin in men with overactive bladder: results
      of an observational study.
AB  - PURPOSE: To evaluate the efficacy and safety of solifenacin for the treatment of
      OAB in men. METHODS: This prospective observational study, reflective of actual
      practice patterns, was conducted in men older than 18 years who were prescribed
      solifenacin for the treatment of OAB symptoms. Men with suspected bladder outlet
      obstruction were excluded. The primary efficacy measure was change in OAB
      symptoms after 12 weeks of solifenacin. Also assessed were changes in severity of
      urinary urgency, IPSS, quality of life, cognitive function, and adverse events.
      Data were analyzed using descriptive methods. RESULTS: A total of 799 men
      recruited at 251 centers, average age 67 years (range 27-92), received
      solifenacin 5 mg or 10 mg/day. Mean episodes of urinary urgency, frequency, and
      nocturia decreased by 4.4, 3.6, and 1.4 episodes/24 h, respectively. As per IPSS,
      severe urinary symptoms were reported by 20.4 % at baseline versus by 2.3 % at
      week 12. Both voiding and storage symptoms showed improvement. Patient-reported
      general health condition was excellent/good for 39 % at baseline increasing to 76
      % at week 12. Adverse event rate was 5.5 %, and discontinuation of solifenacin
      due to an event was 1.6 %. No change in post-void residual urine volume was
      experienced in 80%, while an increase of >=50 mL was observed in 2.2 %; no cases
      of acute urinary retention occurred. Baseline mean MMSE was 27.5 points versus
      27.9 points at week 12. CONCLUSIONS: Solifenacin reduced all OAB symptoms, was
      well tolerated, and had no apparent effect on post-void residual urine volume.
      Cognitive function was unaltered in this population of older men with OAB.

PMID- 24135916
TI  - German urologists under national socialism.
AB  - OBJECTIVES: The first full-time professorship for urology at a German university
      was established in 1937 and in 1942, a rare teaching qualification (Habilitation)
      for urology was granted, both at the prestigious Berlin University. At the same
      time, nearly a third of all physicians who worked in the field of urology were
      classified as "non-Aryan" according to Nazi race laws and were forced out of
      their profession and their homeland. Many of them committed suicide or, if they
      refused to flee, were murdered in concentration camps. German urologists also
      contributed to compulsory sterilization of men according to the "law for the
      prevention of hereditarily diseased offspring" between 1934 and 1945. METHODS:
      Historical sources on the history of urology in Nazi Germany were reviewed and
      analyzed. These include textbooks and medical journals from the 1930s and 1940s,
      as well as files from different state and university archives. RESULTS: For
      urologists, the changing political environment in Germany after 1933 offered
      possibilities to assert their personal and professional interests. Unfortunately,
      in many cases, moral principles were thrown overboard, and physicians advanced
      their own careers and the specialty of urology at the expense of their patients
      and their Jewish colleagues. CONCLUSION: Under national socialism, German
      urologists backed Nazi health and race policies and in exchange gained further
      professionalization for their specialty, including university positions and
      increased independence from surgery. Only in recent years has this chapter of
      German urology's past become a topic of debate among members of the professional
      society.

PMID- 24135917
TI  - The Post-Ureteroscopic Lesion Scale (PULS): a multicenter video-based evaluation
      of inter-rater reliability.
AB  - PURPOSE: The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading
      system for the description of ureteral lesions after ureteroscopy. In this
      article, we present the results of a video-based multicenter evaluation of the
      inter-rater reliability of clinically important PULS grades 0-3. METHODS: Video
      sequences at the end of ureteroscopy (final passage) were recorded for 100
      consecutive patients at a single institution and assessed by experienced
      urologists (n = 20) and senior residents (n = 17) at 19 international centers.
      The cohort included only patients with lesions grades 0-3 (with grades 2 and 3
      subsumed as 2 + since distinction is defined by an extravasation of contrast
      medium in fluoroscopy). The gradings were evaluated for inter-rater reliability
      and in terms of simplicity, validity, comprehensibility, reproducibility, and
      usefulness. RESULTS: Overall, inter-rater reliability was high (Kendall's W =
      0.69, p < 0.001) and was comparable between specialists (Kendall's W = 0.69, p <
      0.001) and residents (Kendall's W = 0.71, p < 0.001). The matched ratings showed
      grade 0 in 43.0 % of patients and grades 1 or 2 + in 44.0 and 13.0 % of patients,
      respectively. Results of the questionnaires indicated a high degree of
      acceptance, with an overall rating of 1.76 (1.64-1.93 for different items, scale
      1-6). CONCLUSIONS: Inter-rater reliability of the endoscopically assessable PULS
      was high among urologists with different levels of experience in different
      countries worldwide. The validated PULS system may be used for standardized
      reporting of ureteral lesions/injuries after ureteroscopy. In addition, PULS will
      enable more selective standardization of indications for postoperative DJ
      stenting based on the randomized controlled trials.

PMID- 24135918
TI  - Lower urinary tract symptoms improve with testosterone replacement therapy in men
      with late-onset hypogonadism: 5-year prospective, observational and longitudinal
      registry study.
AB  - PURPOSE: Many men with "late-onset hypogonadism" (LOH) experience lower urinary
      tract symptoms (LUTS) that can be distressing and may decrease quality of life.
      LUTS often appear in men when testosterone levels begin to decline, which could
      be a significant association. We investigated whether testosterone replacement
      could alleviate LUTS in men with LOH. METHODS: Two hundred and sixty-one
      hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction,
      having also been evaluated for LUTS, received a single testosterone undecanoate
      injection at day 1, at week 6 and quarterly thereafter. Parameters, including
      International Prostate Symptom Score (IPSS), post-voiding residual urine volume,
      transrectal ultrasound, prostate volume and prostate-specific antigen were
      measured at each treatment visit. Two hundred and fifty-nine patients were
      included in the full analysis set. These were subsequently divided into weight
      losers (L >= 5 % weight loss at last visit from baseline) and non-losers (NL). t
      test analyses were used to compare the IPSS means of these subgroups. The
      potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor
      (PDE5i) vardenafil was also accounted for. RESULTS: Mean IPSS showed a
      significant decrease with time following initiation of testosterone treatment (p
      < 0.05). No significant differences were observed in either IPSS between L and NL
      groups or in mean IPSS between vardenafil users and non-users. CONCLUSION:
      Testosterone replacement is associated with improvements in LUTS which are not
      confounded by weight loss or PDE5i. The mechanisms of this association require
      further investigation.

PMID- 24135920
TI  - Designer cells for stereocomplementary de novo enzymatic cascade reactions based
      on laboratory evolution.
AB  - Designer cells for a synthetic cascade reaction harnessing selective redox
      reactions were devised, featuring two successive regioselective P450-catalyzed CH
      activating oxidations of 1-cyclohexene carboxylic acid methyl ester followed by
      stereoselective olefin-reduction catalysed by (R)- or (S)-selective mutants of an
      enoate reductase. 

PMID- 24135919
TI  - Reconstructing targetable pathways in lung cancer by integrating diverse omics
      data.
AB  - Global 'multi-omics' profiling of cancer cells harbours the potential for
      characterizing the signalling networks associated with specific oncogenes. Here
      we profile the transcriptome, proteome and phosphoproteome in a panel of non
      small cell lung cancer (NSCLC) cell lines in order to reconstruct targetable
      networks associated with KRAS dependency. We develop a two-step bioinformatics
      strategy addressing the challenge of integrating these disparate data sets. We
      first define an 'abundance-score' combining transcript, protein and phospho
      protein abundances to nominate differentially abundant proteins and then use the
      Prize Collecting Steiner Tree algorithm to identify functional sub-networks. We
      identify three modules centred on KRAS and MET, LCK and PAK1 and beta-Catenin. We
      validate activation of these proteins in KRAS-dependent (KRAS-Dep) cells and
      perform functional studies defining LCK as a critical gene for cell proliferation
      in KRAS-Dep but not KRAS-independent NSCLCs. These results suggest that LCK is a
      potential druggable target protein in KRAS-Dep lung cancers. 

PMID- 24135921
TI  - Cadmium background concentrations to establish reference quality values for soils
      of Sao Paulo State, Brazil.
AB  - Proper assessment of soil cadmium (Cd) concentrations is essential to establish
      legislative limits. The present study aimed to assess background Cd
      concentrations in soils from the state of Sao Paulo, Brazil, and to correlate
      such concentrations with several soil attributes. The topsoil samples (n = 191)
      were assessed for total Cd contents and for other metals using the USEPA 3051A
      method. The background concentration was determined according to the third
      quartile (75th). Principal component analysis, Spearman correlation, and multiple
      regressions between Cd contents and other soil attributes (pH, cation exchange
      capacity (CEC), clay content, sum of bases, organic matter, and total Fe, Al, Zn,
      and Pb levels) were performed. The mean Cd concentration of all 191 samples was
      0.4 mg kg(-1), and the background concentration was 0.5 mg kg(-1). After the
      samples were grouped by parent material (rock origin) and soil type, the
      background Cd content varied, i.e., soils from igneous, metamorphic, and
      sedimentary rocks harbored 1.5, 0.4, and 0.2 mg kg(-1) of Cd, respectively. The
      background Cd content in Oxisols (0.8 mg kg(-1)) was higher than in Ultisols (0.3
      mg kg(-1)). Multiple regression demonstrated that Fe was primarily attributed to
      the natural Cd contents in the soils (R (2) = 0.79). Instead of a single Cd
      background concentration value representing all Sao Paulo soils, we propose that
      the concentrations should be specific for at least Oxisols and Ultisols, which
      are the primary soil types. 

PMID- 24135922
TI  - State of rare earth elements in different environmental components in mining
      areas of China.
AB  - China has relatively abundant rare earth elements (REEs) reserves and will
      continue to be one of the major producers of REEs for the world market in the
      foreseeable future. However, due to the large scale of mining and refining
      activities, large amounts of REEs have been released to the surrounding
      environment and caused harmful effects on local residents. This paper summarizes
      the data about the contents and translocation of REEs in soils, waters,
      atmosphere, and plants in REE mining areas of China and discusses the
      characteristics of their forms, distribution, fractionation, and influencing
      factors. Obviously high concentrations of REEs with active and bioavailable forms
      are observed in all environmental media. The mobility and bioavailability of REEs
      are enhanced. The distribution patterns of REEs in soils and water bodies are all
      in line with their parent rocks. Significant fractionation phenomenon among
      individual members of REEs was found in soil-plant systems. However, limited
      knowledge was available for REEs in atmosphere. More studies focusing on the
      behavior of REEs in ambient air of REE mining areas in China are highly
      suggested. In addition, systematic study on the translocation and circulation of
      REEs in various media in REEs mining areas and their health risk assessment
      should be carried out. Standard analytical methods of REEs in environments need
      to be established, and more specific guideline values of REEs in foods should
      also be developed. 

PMID- 24135923
TI  - Carbon sequestration in the soils of aquaculture ponds, crop land, and forest
      land in southern Ohio, USA.
AB  - Soil samples were collected from four aquaculture ponds (yellow perch culture), a
      control pond (without aquaculture activities, fallow pond), crop land (under
      corn), and forest land to estimate the carbon (C) sequestration potential in the
      Piketon county, Ohio, USA. The averaged total of C was 6.5 +/- 2, 8.8 +/- 2, 8.53
      +/- 0.2 and 10.49 +/- 1.1 Mg/ha (Mg=10(6)g) in < 0.25 mm fraction; 15.2 +/- 2,
      16.0 +/- 3, 11.49 +/- 0.8 and 17.23 +/- 3.4 Mg/ha in micro aggregates (0.25-2.5
      mm); and 22.1 +/- 3, 26.4 +/- 3, 12.16 +/- 1.6 and 18.51 +/- 4.3 Mg/ha in macro
      aggregates ( > 2.5mm), for aquaculture ponds, control ponds, cropland and forest
      land, respectively. The soil/sediment C pool followed the order of forest > crop
      land soils > aquaculture pond soils. 

PMID- 24135925
TI  - Cost of spontaneous intracerebral hemorrhage in Canada during 1 decade.
AB  - BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is widely
      considered to be the most devastating form of stroke in North America. Currently
      there is no clear understanding of the cost of treatment in Canada and thus no
      way of understanding how to manage ICH spending in this country. METHODS: We used
      a cohort study design to report and to examine the cost of ICH hospital care in a
      Canadian health center during 1 decade. Economic, treatment, and patients data
      were obtained from clinical and administrative sources. RESULTS: Analyses were
      performed using 987 consecutive patients with ICH from 1999 to 2008. The total
      inflation-adjusted cost of care was highly variable (median cost per discharge,
      $10,544.45 and $363.54 [min] to $265 470.43 [max] United States Dollars). Total
      cost did not change significantly during the decade. Patients age (cost change
      per year older, -$114.06 and -$189.01 to -$38.78) and in-hospital mortality (cost
      change for death, -$5092.84 and -$6270.65 to -$3697.09) were significantly
      associated with lower cost, whereas Charlson Comorbidity Index (cost change for
      >=1, $5726.27 and $3965.36 to $7755.45), having surgery (cost change for surgery,
      $25,499.78 and $20,813.95 to $30,933.06), and admission National Institutes of
      Health Stroke Scale (cost change for >=15 points, $7800.20 and $1637.78 to
      $17,026.38) were significantly associated with higher cost. CONCLUSIONS: To our
      knowledge, this is the most thorough published study to date to report and to
      examine predictors of ICH treatment costs in Canada. This study provides evidence
      that it may be reasonable to consider patients age, probability of death, level
      of comorbidity, need for surgery, and baseline ICH severity when forecasting
      health spending.

PMID- 24135924
TI  - Effects of MLC601 on early vascular events in patients after stroke: the CHIMES
      study.
AB  - BACKGROUND AND PURPOSE: Early vascular events are an important cause of morbidity
      and mortality in the first 3 months after a stroke. We aimed to investigate the
      effects of MLC601 on the occurrence of early vascular events within 3 months of
      stroke onset. METHODS: Post hoc analysis was performed on data from subjects
      included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES)
      study, a randomized, placebo-controlled, double-blinded trial that compared
      MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate
      severity in the preceding 72 hours. Early vascular events were defined as a
      composite of recurrent stroke, acute coronary syndrome, and vascular death
      occurring within 3 months of stroke onset. RESULTS: The frequency of early
      vascular events during the 3-month follow-up was significantly less in the MLC601
      group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk
      difference=-2.7%; 95% confidence interval, -5.1% to -0.4%; P=0.025) without an
      increase in nonvascular deaths. Kaplan-Meier survival analysis showed a
      difference in the risk of vascular outcomes between the 2 groups as early as the
      first month after stroke (Log-rank P=0.024; hazard ratio, 0.51; 95% confidence
      interval, 0.28-0.93). CONCLUSIONS: Treatment with MLC601 was associated with
      reduced early vascular events among subjects in the CHIMES study. The mechanisms
      for this effect require further study. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00554723.

PMID- 24135926
TI  - Australian public's awareness of stroke warning signs improves after national
      multimedia campaigns.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to examine the reach and impact
      of the National Stroke Foundation (NSF) multimedia stroke warning sign campaigns
      across Australia. METHODS: A total of 12 439 surveys were performed across 6
      states during 6 years on random state-weighted samples of Australians>=40 years
      old. RESULTS: Awareness of stroke advertising increased 31% to 50% between 2004
      and 2010 (P<0.001), as did the unprompted recall of >=2 most common stroke
      warning signs 20% to 53% (P<0.001). Awareness of stroke advertising was
      independently associated with recalling >=2 common signs (adjusted odds
      ratio=1.88, 95% confidence interval [1.74-2.04]; P<0.001). Awareness was not
      greater in respondents with previous stroke or risk factors, except atrial
      fibrillation. CONCLUSIONS: The Australian public's awareness of stroke warning
      signs has improved since commencement of the NSF campaigns commensurate with
      greater awareness of stroke advertising. Public education efforts are worthwhile,
      and future efforts should focus on groups identified with low awareness or those
      at high risk of stroke.

PMID- 24135927
TI  - Does the influence of stroke on dementia vary by different levels of prestroke
      cognitive functioning?: a cohort study.
AB  - BACKGROUND AND PURPOSE: The association between stroke and subsequent dementia or
      Alzheimer disease is well established. What is less understood is the extent to
      which this association is dependent on prestroke cognitive functioning. The study
      estimated the occurrence in poststroke dementia as a function of prestroke
      cognitive status and incident stroke. METHODS: Study data were derived from the
      English Longitudinal Study of Ageing, a 10-year long prospective cohort study of
      older adults living in England. Baseline data (2002/2003) were used to group
      participants into tertiles of cognitive, memory, and executive functioning before
      an incident stroke. Data from 4 follow-up surveys were used to identify new
      stroke and poststroke dementia events. RESULTS: The analyses were based on 10 809
      participants aged>=50 years at baseline. High prestroke executive functioning was
      associated with lower relative risk (RR) of dementia (RR, 0.24; 95% confidence
      interval, 0.13-0.45; P<0.001). Stroke was associated with increased RR of
      poststroke dementia (RR, 2.63; 95% confidence interval, 1.80-3.84; P<0.001). The
      association of stroke with poststroke dementia was greater for participants with
      higher prestroke executive functioning (interaction term RR, 4.4; 95% confidence
      interval, 1.35-14.63; P=0.014). For participants with higher executive
      functioning, the probability of dementia was 0.3% without stroke and 3.1% after
      stroke, compared with 1.9% and 5.2% for lower executive functioning. CONCLUSIONS:
      Stroke and prestroke cognition were independently associated with increased
      probability of poststroke dementia. Stroke results in disproportionate increase
      in the risk of dementia when premorbid cognitive functioning is high.

PMID- 24135928
TI  - Stroke awareness among inpatient nursing staff at an academic medical center.
AB  - BACKGROUND AND PURPOSE: Because 10% of strokes occur in hospitalized patients, we
      sought to evaluate stroke knowledge and predictors of stroke knowledge among
      inpatient and emergency department nursing staff. METHODS: Nursing staff
      completed an online stroke survey. The survey queried outcome expectations (the
      importance of rapid stroke identification), self-efficacy in recognizing stroke,
      and stroke knowledge (to name 3 stroke warning signs or symptoms). Adequate
      stroke knowledge was defined as the ability to name >=2 stroke warning signs.
      Logistic regression was used to identify the association between stroke symptom
      knowledge and staff characteristics (education, clinical experience, and nursing
      unit), stroke self-efficacy, and outcome expectations. RESULTS: A total of 875
      respondents (84% response rate) completed the survey and most of the respondents
      were nurses. More than 85% of respondents correctly reported >=2 stroke warning
      signs or symptoms. Greater self-efficacy in identifying stroke symptoms (odds
      ratio, 1.13; 95% confidence interval, 1.01-1.27) and higher ratings for the
      importance of rapid identification of stroke symptoms (odds ratio, 1.23; 95%
      confidence interval, 1.002-1.51) were associated with stroke knowledge. Clinical
      experience, educational experience, nursing unit, and personal knowledge of a
      stroke patient were not associated with stroke knowledge. CONCLUSIONS: Stroke
      outcome expectations and self-efficacy are associated with stroke knowledge and
      should be included in nursing education about stroke.

PMID- 24135930
TI  - Intracranial stent placement for symptomatic intracranial stenosis as part of a
      clinical trial versus outside a clinical trial.
AB  - BACKGROUND AND PURPOSE: A high rate of postprocedure complications in the
      Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis
      (SAMMPRIS) trial has raised concerns whether such results are representative of
      intracranial stent placement in actual routine practice. METHODS: Using the
      Nationwide Inpatient Sample from 2008 to 2010, patients with cerebral ischemic
      events treated with intracranial stent as part of a clinical trial or outside the
      trial were identified. The composite end point (postoperative stroke, cardiac
      complications, and mortality) was reported. RESULTS: Of the 3447 patients who
      underwent intracranial stent placement, 223 patients (6.5%) were enrolled in a
      clinical trial. The rate of composite end point was higher in patients treated
      outside clinical trials compared with those treated within clinical trials (14.2%
      versus 4.5%; P=0.1). The proportion of patients discharged to home was higher in
      those treated in clinical trials (76.8% versus 49.6%; P=0.001). CONCLUSIONS:
      Intracranial stent placement procedures outside a clinical trial have higher
      rates of postoperative stroke, cardiac complication, and mortality.

PMID- 24135929
TI  - A clinical rule (sex, contralateral occlusion, age, and restenosis) to select
      patients for stenting versus carotid endarterectomy: systematic review of
      observational studies with validation in randomized trials.
AB  - BACKGROUND AND PURPOSE: Compared with carotid endarterectomy (CEA), carotid
      angioplasty and stenting (CAS) is associated with a higher risk of procedural
      stroke or death especially in patients with symptomatic stenosis. However, after
      the perioperative period, risk is similar with both treatments, suggesting that
      CAS could be an acceptable option in selected patients. METHODS: We performed
      systematic reviews of observational studies of procedural risks of CEA or CAS and
      extracted data on 9 predefined risk factors (age, contralateral carotid
      occlusion, coronary artery disease, diabetes mellitus, sex, hypertension,
      peripheral artery disease, and type and side of stenosis). We calculated pooled
      relative risks of procedural stroke or death. Factors with differential effects
      on risk of CAS versus CEA were identified by interaction tests and used to derive
      a rule. The rule was tested using individual patient data from randomized trials
      of CAS versus CEA from the Carotid Stenting Trialists' Collaboration (CSTC).
      RESULTS: We identified 170 studies. The effects of sex, contralateral occlusion,
      age, and restenosis (SCAR) on the procedural risk of stroke or death differed.
      Patients with contralateral occlusion or restenosis and women<75 years were at
      relatively low risk for CAS (SCAR negative), with all others being high risk
      (SCAR positive). Among the 3049 patients in the CSTC validation, 694 (23%)
      patients were SCAR negative. The pooled RR of procedural stroke and death with
      CAS versus CEA was 0.93 (0.49-1.77; P=0.83) in SCAR-negative and 2.41 (1.68-3.45;
      P<0.0001) in SCAR-positive patients (P [interaction]=0.05). CONCLUSIONS: The SCAR
      rule is potentially useful to identify patients in whom CAS has a similar risk of
      perioperative stroke or death to CEA.

PMID- 24135931
TI  - Preceding and poststroke infections in young adults with first-ever ischemic
      stroke: effect on short-term and long-term outcomes.
AB  - BACKGROUND AND PURPOSE: Poststroke infections (PSIs) worsen the outcome in acute
      ischemic stroke, but the effect of preceding infection (PI) is controversial.
      Data on young patients are scarce. We characterized PI and PSI in young adults
      with first-ever stroke and studied whether they are associated with 3-month and
      long-term outcomes, recurrent vascular events, and death. METHODS: From our
      database of 1008 consecutive patients aged 15 to 49 years, we included in the
      present study those who had brain imaging done within the first 2 days from
      stroke onset. Outcomes were unfavorable at 3 months and during long-term follow
      up, vascular events, and all-cause death. Logistic regression and Cox
      proportional models were used to determine associations between infections and
      clinical outcomes. RESULTS: A total of 681 patients (62.3% men) fulfilled the
      inclusion criteria. Of these, 70 (10.3%) had PI, most commonly upper respiratory
      tract infection, and 103 (15.1%) had PSI, most commonly pneumonia. After
      adjusting for sex, age, and risk factors, both PI (odds ratio, 2.86; 95%
      confidence interval, 1.48-5.54) and PSI (odds ratio, 2.26; 95% confidence
      interval, 1.08-4.76) were independently associated with unfavorable 3-month
      outcome. PSI was also associated with long-term (follow-up, 7.8+/-4.0 years)
      higher risk of all-cause death. CONCLUSIONS: In young patients with ischemic
      stroke, both PI and PSIs are associated with unfavorable short-term outcome. PSIs
      are also associated with higher long-term mortality.

PMID- 24135932
TI  - N2 neutrophils, novel players in brain inflammation after stroke: modulation by
      the PPARgamma agonist rosiglitazone.
AB  - BACKGROUND AND PURPOSE: Neutrophils have been traditionally recognized as major
      mediators of a deleterious inflammatory response in acute ischemic stroke, but
      their potential as a therapeutic target remains unexplored. Recent evidence
      indicates that neutrophils may acquire different phenotypes and contribute to
      resolution of inflammation through the release of anti-inflammatory mediators.
      Thus, similar to M2 macrophages, neutrophils have been proposed to shift toward
      an N2 phenotype, a polarization that is peroxisome proliferator-activated
      receptor-gamma dependent in macrophages. We hypothesize that peroxisome
      proliferator-activated receptor-gamma activation with rosiglitazone induces
      changes in neutrophilic mobilization and phenotype that might influence stroke
      outcome. METHODS: Brain sections and cell suspensions were prepared from mice
      exposed to permanent distal middle cerebral artery occlusion. Double
      immunostaining with stereological counting of brain sections and flow-cytometry
      analysis of brain cell suspensions were performed. RESULTS: Rosiglitazone
      accelerated neutrophil infiltration to the ischemic core, concomitantly to
      neuroprotection. Some neutrophils (~31%) expressed M2 markers, namely Ym1 and
      CD206 (mannose receptor). After treatment with the peroxisome proliferator
      activated receptor-gamma agonist rosiglitazone, most neutrophils (~77%) acquired
      an N2 phenotype. Interestingly, rosiglitazone increased neutrophil engulfment by
      microglia/macrophages, a clearance that preferentially affected the N2 subset.
      CONCLUSIONS: We present the first evidence of neutrophil reprogramming toward an
      N2 phenotype in brain inflammation, which can be modulated by activation of the
      peroxisome proliferator-activated receptor-gamma nuclear receptor. We also show
      that N2 polarization is associated with an increased neutrophil clearance, thus
      suggesting that this switch is a crucial event for resolution of inflammation
      that may participate in neuroprotection.

PMID- 24135933
TI  - The optimization of an intravaginal ring releasing progesterone using a
      mathematical model.
AB  - PURPOSE: Progering(r) is the only intravaginal ring intended for contraception
      therapies during lactation. It is made of silicone and releases progesterone
      through the vaginal walls. However, some drawbacks have been reported in the use
      of silicone. Therefore, ethylene vinyl acetate copolymer (EVA) was tested in
      order to replace it. METHODS: EVA rings were produced by a hot-melt extrusion
      procedure. Swelling and degradation assays of these matrices were conducted in
      different mixtures of ethanol/water. Solubility and partition coefficient of
      progesterone were measured, together with the initial hormone load and
      characteristic dimensions. A mathematical model was used to design an EVA ring
      that releases the hormone at specific rate. RESULTS: An EVA ring releasing
      progesterone in vitro at about 12.05 +/- 8.91 mg day(-1) was successfully
      designed. This rate of release is similar to that observed for Progering(r). In
      addition, it was observed that as the initial hormone load or ring dimension
      increases, the rate of release also increases. Also, the device lifetime was
      extended with a rise in the initial amount of hormone load. CONCLUSIONS: EVA
      rings could be designed to release progesterone in vitro at a rate of 12.05 +/-
      8.91 mg day(-1). This ring would be used in contraception therapies during
      lactation. The use of EVA in this field could have initially several advantages:
      less initial and residual hormone content in rings, no need for additional steps
      of curing or crosslinking, less manufacturing time and costs, and the possibility
      to recycle the used rings.

PMID- 24135934
TI  - Solidified self-nanoemulsifying formulation for oral delivery of combinatorial
      therapeutic regimen: part II in vivo pharmacokinetics, antitumor efficacy and
      hepatotoxicity.
AB  - PURPOSE: The present work focuses on the in vivo evaluation of tamoxifen and
      quercetin combination loaded into solid self-nanoemulsifying drug delivery system
      (s-Tmx-QT-SNEDDS). METHODS: Lyophilization was employed to prepare s-Tmx-QT
      SNEDDS using Aerosil 200 as carrier. The developed formulation was evaluated for
      in vitro cell cytotoxicity, in vivo pharmacokinetics, antitumor efficacy and
      toxicity studies. RESULTS: In vivo pharmacokinetics revealed ~8-fold and ~4-fold
      increase in oral bioavailability of tamoxifen and quercetin, respectively as
      compared to free counterparts. s-Tmx-QT-SNEDDS exhibited significantly higher
      cell cytotoxicity, as compared to free drug combination revealing ~32-fold and
      ~22-fold higher dose reduction index for tamoxifen and quercetin, respectively
      estimated using median effect dose analysis. s-Tmx-QT-SNEDDS could suppress tumor
      growth in DMBA induced tumor bearing animals by ~80% in contrast to ~35% observed
      with tamoxifen citrate. The significant appreciation in antitumor efficacy was
      further supported by normalized levels of tumor angiogenesis markers (MMP-2 and
      MMP-9). Finally, complete obliteration in tamoxifen induced hepatotoxicity was
      observed upon administration of developed formulation in contrast to that of
      clinically available tamoxifen citrate when measured as function of
      hepatotoxicity markers and histopathological changes. CONCLUSIONS: In nutshell,
      co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great
      potential in improving the therapeutic efficacy and safety of tamoxifen.

PMID- 24135935
TI  - Chernobyl fallout and cancer incidence in Finland.
AB  - Twenty-five years have passed since the Chernobyl accident, but its health
      consequences remain to be well established. Finland was one of the most heavily
      affected countries by the radioactive fallout outside the former Soviet Union. We
      analyzed the relation of the estimated external radiation exposure from the
      fallout to cancer incidence in Finland in 1988-2007. The study cohort comprised
      all ~ 3.8 million Finns who had lived in the same dwelling for 12 months
      following the accident (May 1986-April 1987). Radiation exposure was estimated
      using data from an extensive mobile dose rate survey. Cancer incidence data were
      obtained for the cohort divided into four exposure categories (the lowest with
      the first-year committed dose <0.1 mSv and the highest >= 0.5 mSv) allowing for a
      latency of 5 years for leukemia and thyroid cancer, and 10 years for other
      cancers. Of the eight predefined cancer sites regarded as radiation-related from
      earlier studies, only colon cancer among women showed an association with
      exposure from fallout [excess rate ratio per increment in exposure category 0.06,
      95% confidence interval (CI) 0.02-0.11]. No such effect was observed for men, or
      other cancer sites. Our analysis of a large cohort over two decades did not
      reveal an increase in cancer incidence following the Chernobyl accident, with the
      possible exception of colon cancer among women. The largely null findings are
      consistent with extrapolation from previous studies suggesting that the effect is
      likely to remain too small to be empirically detectable and of little public
      health impact.

PMID- 24135936
TI  - Ginsenoside Rb1 attenuates oxygen-glucose deprivation-induced apoptosis in SH
      SY5Y cells via protection of mitochondria and inhibition of AIF and cytochrome c
      release.
AB  - To investigate the role of mitochondria in the protective effects of ginsenoside
      Rb1 on cellular apoptosis caused by oxygen-glucose deprivation, in this study,
      MTT assay, TUNEL staining, flow cytometry, immunocytochemistry and western
      blotting were used to examine the cellular viability, apoptosis, ROS level,
      mitochondrial membrane potential, and the distribution of apoptosis inducing
      factor, cytochrome c, Bax and Bcl-2 in nucleus, mitochondria and cytoplasm. We
      found that pretreatment with GRb1 improved the cellular viability damaged by OGD.
      Moreover, GRb1 inhibited apoptosis in SH-SY5Y cells induced by OGD. Further
      studies showed that the elevation of cellular reactive oxygen species levels and
      the reduction of mitochondrial membrane potential caused by OGD were both
      counteracted by GRb1. Additionally, GRb1 not only suppressed the translocation of
      apoptosis inducing factor into nucleus and cytochrome c into cytoplasm, but also
      inhibited the increase of Bax within mitochondria and alleviated the decrease of
      mitochondrial Bcl-2. Our study indicates that the protection of GRb1 on OGD
      induced apoptosis in SH-SY5Y cells is associated with its protection on
      mitochondrial function and inhibition of release of AIF and cytochrome c. 

PMID- 24135937
TI  - Apoptosis sensitization by Euphorbia factor L1 in ABCB1-mediated multidrug
      resistant K562/ADR cells.
AB  - In this article, reversal activities of Euphorbia factor L1 (EFL1) against ABCB1
      mediated multidrug resistance (MDR) and apoptosis sensitization in K562/ADR cells
      are reported. EFL1 decreased the IC50 values of anticancer agents in K562/ADR
      cells over-expressing ABCB1. However, EFL1 did not affect the IC50 values of
      anticancer agents in sensitive K562 cells. Additionally, EFL1 increased the
      intracellular accumulation of rhodamine 123 and doxorubicin in K562/ADR cells
      without affecting their accumulation in K562 cells. Furthermore, EFL1 sensitized
      the apoptosis triggered by vincristine in K562/ADR cells via mitochondrial
      pathway, as confirmed by Annexin V-FITC/PI detection and western blot. At the
      same time, EFL1 did not influence the apoptosis induced by vincristine in K562
      cells. Western blot results showed that EFL1 did not affect the phosphorylation
      level of AKT and ERK in K562 and K562/ADR cells. Finally, EFL1 did not down
      regulate protein expression of ABCB1. 

PMID- 24135938
TI  - Astragaloside IV stimulates angiogenesis and increases nitric oxide accumulation
      via JAK2/STAT3 and ERK1/2 pathway.
AB  - Astragaloside IV (AS-IV), one of the major active constituents of Astragalus
      membranaceus in Traditional Chinese Medicine, has been widely used to treat
      ischemic diseases. However, the potential mechanism is this action is unclear. In
      this study, we tested the hypothesis that AS-IV might promote angiogenesis
      through multiple signaling pathways. Our data indicate that AS-IV treatment
      promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and
      tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling
      pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression
      and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is
      significantly blocked by specific kinase inhibitors. Our study indicated that AS
      IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2
      pathways, which provides a mechanistic basis for the potential use of this
      compound in the treatment of clinical ischemic diseases. 

PMID- 24135939
TI  - Synthesis of cycloveratrylene macrocycles and benzyl oligomers catalysed by
      bentonite under microwave/infrared and solvent-free conditions.
AB  - Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation
      of cycloveratrylene macrocycles and benzyl oligomers from the corresponding
      benzyl alcohols in good yields under microwave heating and infrared irradiation
      in the absence of solvent in both cases. The catalytic reaction is sensitive to
      the type of substituent on the aromatic ring. Thus, when benzyl alcohol was
      substituted with a methylenedioxy, two methoxy or three methoxy groups, a
      cyclooligomerisation process was induced. Unsubstituted, methyl and methoxy
      benzyl alcohols yielded linear oligomers. In addition, computational chemistry
      calculations were performed to establish a validated mechanistic pathway to
      explain the growth of the obtained linear oligomers. 

PMID- 24135940
TI  - Cs+ removal from aqueous solutions through adsorption onto Florisil(r)
      impregnated with trihexyl(tetradecyl)phosphonium chloride.
AB  - This research determined the adsorption performance of Florisil(r) impregnated
      with trihexyl(tetradecyl)phosphonium chloride (Cyphos IL-101) in the process of
      Cs+ removal from aqueous solutions. The obtained Florisil(r) impregnated with the
      studied ionic liquid was characterized through energy dispersive X-ray analysis
      and Fourier transform infrared spectroscopy in order to verify that the
      impregnation with the ionic liquid had occurred. The adsorption process has been
      investigated as a function of pH, solid:liquid ratio, adsorbate concentration,
      contact time and temperature. The isotherm data was well described by a Langmuir
      isotherm model. The maximum adsorption capacities of the Florisil(r) impregnated
      with the studied ionic liquid was found to be 3.086 mg Cs+/g of adsorbent. The
      results indicated that the adsorption fitted well with the pseudo-second order
      kinetic model.

PMID- 24135941
TI  - Chemometric evaluation of urinary steroid hormone levels as potential biomarkers
      of neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific
      hormone products such as peptides, biogenic amines and hormones. So far, the
      diagnosis of NETs has been difficult because most NET markers are not specific
      for a given tumor and none of the NET markers can be used to fulfil the criteria
      of high specificity and high sensitivity for the screening procedure. However, by
      combining the measurements of different NET markers, they become highly sensitive
      and specific diagnostic tests. The aim of the work was to identify whether
      urinary steroid hormones can be identified as potential new biomarkers of NETs,
      which could be used as prognostic and clinical course monitoring factors. Thus, a
      rapid and sensitive reversed-phase high-performance liquid chromatographic method
      (RP-HPLC) with UV detection has been developed for the determination of cortisol,
      cortisone, corticosterone, testosterone, epitestosterone and progesterone in
      human urine. The method has been validated for accuracy, precision, selectivity,
      linearity, recovery and stability. The limits of detection and quantification
      were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was
      confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater
      than 0.9995 for all analytes. The described method was successfully applied for
      the quantification of six endogenous steroid levels in human urine. Studies were
      performed on 20 healthy volunteers and 19 patients with NETs. Next, for better
      understanding of tumor biology in NETs and for checking whether steroid hormones
      can be used as potential biomarkers of NETs, a chemometric analysis of urinary
      steroid hormone levels in both data sets was performed. 

PMID- 24135942
TI  - Elicitation of induced resistance against Pectobacterium carotovorum and
      Pseudomonas syringae by specific individual compounds derived from native Korean
      plant species.
AB  - Plants have developed general and specific defense mechanisms for protection
      against various enemies. Among the general defenses, induced resistance has
      distinct characteristics, such as broad-spectrum resistance and long-lasting
      effectiveness. This study evaluated over 500 specific chemical compounds derived
      from native Korean plant species to determine whether they triggered induced
      resistance against Pectobacterium carotovorum supsp. carotovorum (Pcc) in tobacco
      (Nicotiana tabacum) and Pseudomonas syringae pv. tomato (Pst) in Arabidopsis
      thaliana. To select target compound(s) with direct and indirect (volatile)
      effects, a new Petri-dish-based in vitro disease assay system with four
      compartments was developed. The screening assay showed that capsaicin, fisetin
      hydrate, jaceosidin, and farnesiferol A reduced the disease severity
      significantly in tobacco. Of these four compounds, capsaicin and jaceosidin
      induced resistance against Pcc and Pst, which depended on both salicylic acid
      (SA) and jasmonic acid (JA) signaling, using Arabidopsis transgenic and mutant
      lines, including npr1 and NahG for SA signaling and jar1 for JA signaling. The
      upregulation of the PR2 and PDF1.2 genes after Pst challenge with capsaicin pre
      treatment indicated that SA and JA signaling were primed. These results
      demonstrate that capsaicin and jaceosidin can be effective triggers of strong
      induced resistance against both necrotrophic and biotrophic plant pathogens. 

PMID- 24135943
TI  - Preparative separation of spirobisnaphthalenes from endophytic fungus
      Berkleasmium sp. Dzf12 by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) was applied for the first time
      for the preparative separation of spirobisnaphthalenes from a crude extract of
      the endophytic fungus Berkleasmium sp. Dzf12, associated with the medicinal plant
      Dioscorea zingiberensis. Six spirobisnaphthalenes were successfully separated by
      HSCCC with a two-phase solvent system composed of n-hexane-chloroform-methanol
      water (1.5:3.0:2.5:2.0, v/v). About 18.0 mg of diepoxin kappa (1), 245.7 mg of
      palmarumycin C13 (2), 42.4 mg of palmarumycin C16 (3), 42.2 mg of palmarumycin
      C15 (4), 32.6 mg of diepoxin delta (5), and 22.3 mg of diepoxin gamma (6) with
      purities of 56.82, 71.39, 76.57, 75.86, 91.01 and 82.48%, respectively, as
      determined by high-performance liquid chromatography (HPLC), were obtained from
      500 mg of the crude extract in a one-step elution within 7 h of separation
      procedure by HSCCC. The purified spirobisnaphthalenes were further structurally
      characterized by means of physicochemical and spectrometric analysis.

PMID- 24135944
TI  - Relationship between skin diseases and extracutaneous complications of diabetes
      mellitus: clinical analysis of 750 patients.
AB  - BACKGROUND: The relationship between skin diseases and extracutaneous
      complications in diabetes mellitus (DM) is unclear. OBJECTIVE: We aimed to
      investigate the relationship between skin disorders and diabetic neuropathy,
      nephropathy, and retinopathy in patients with DM. METHODS: A total of 750
      patients with DM were prospectively enrolled. Demographic and clinical features,
      skin disorders, glycosylated hemoglobin (HbA1c) levels, and presence of
      nephropathy, neuropathy, and retinopathy were noted. RESULTS: Of the patients,
      38.0% had neuropathy, 23.3% had nephropathy, and 22.9% had retinopathy. Any skin
      disorder was present in 79.2% (n = 594) of patients. The most common skin
      manifestations were cutaneous infections (47.5%), xerosis (26.4%), and
      inflammatory skin diseases (20.7%). The frequency of cutaneous infections, fungal
      infections, diabetic foot, rubeosis faciei, and pigmented purpuric dermatitis was
      higher in patients with nephropathy than in those without nephropathy. Cutaneous
      infections, diabetic foot, rubeosis faciei, and diabetic dermopathy were more
      common in patients with neuropathy. Fungal infections, diabetic foot, rubeosis
      faciei, diabetic dermopathy, and pigmented purpuric dermatitis were more frequent
      in patients with retinopathy. Patients with HbA1c >=8 mmol/mL had more skin
      disorders than those with HbA1c <8 mmol/mL (P < 0.05 for all). CONCLUSION: Skin
      disorders may be clues to the presence of associated microvascular complications
      of DM.

PMID- 24135945
TI  - Can experience from adults regarding acute liver failure fit children?
AB  - Till date, comparison of clinical characteristics in acute liver failure (ALF)
      between adults and children has not been performed. In this study, authors
      retrospectively collected data on adult acute liver failure (AALF) and pediatric
      acute liver failure (PALF) in seven hospitals in different areas of China from
      January 2007 through December 2012. A total of 177 AALF cases and 32 PALF cases
      were eventually included. Several vital clinical variables were significantly
      different between AALF and PALF, including serum alkaline phosphatase, serum
      creatinine, serum urea nitrogen, serum lactate dehydrogenase, platelet count,
      prothrombin activity, international normalized ratio and blood ammonia. It is
      concluded that experience from AALF could not be proper for PALF. 

PMID- 24135946
TI  - Acute lymphoblastic leukemia mimicking metabolic bone disease.

PMID- 24135947
TI  - Halogenation effects in intramolecular furan Diels-Alder reactions: broad scope
      synthetic and computational studies.
AB  - For the first time a comprehensive synthetic and computational study of the
      effect of halogen substitution on both furan and dienophile for the
      intramolecular Furan Diels-Alder (IMDAF) reaction has been undertaken. Contrary
      to our initial expectations, halogen substitution on the dienophile was found to
      have a significant effect, making the reactions slower and less thermodynamically
      favourable. However, careful choice of the site of furan halogenation could be
      used to overcome dienophile halogen substitution, leading to highly
      functionalised cycloadducts. These reactions are thought to be controlled by the
      interplay of three factors: positive charge stabilisation in the transition state
      and product, steric effects and a dipolar interaction term identified by high
      level calculations. Frontier orbital effects do not appear to make a major
      contribution in determining the viability of these reactions, which is consistent
      with our analysis of calculated transition state structural data. 

PMID- 24135950
TI  - Quality improvement in nursing homes: testing of an alarm elimination program.
AB  - Falls are the most common cause of injury deaths and nonfatal injuries in older
      adults. In an effort to detect a resident's movement, many nursing homes use bed
      or chair alarms to alert staff that the resident may get up and possibly fall.
      However, there is little evidence that bed or chair alarms prevent falls, and
      mounting evidence that alarms can impede the functional status and negatively
      impact feelings of dignity among older adults in nursing homes. The purpose of
      this article was to describe the development and pilot testing of an alarm
      elimination program for nursing homes. A program aimed at decreasing or
      eliminating the use of alarms may enhance quality of life of older adults in
      nursing homes. 

PMID- 24135949
TI  - EIF2AK4 mutations in pulmonary capillary hemangiomatosis.
AB  - BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of
      capillary proliferation of unknown cause and with a high mortality. Families with
      multiple affected individuals with PCH suggest a heritable cause although the
      genetic etiology remains unknown. METHODS: We used exome sequencing to identify a
      candidate gene for PCH in a family with two affected brothers. We then screened
      11 unrelated patients with familial (n = 1) or sporadic (n = 10) PCH for
      mutations. RESULTS: Using exome sequencing, we identified compound mutations in
      eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) (formerly
      known as GCN2) in both affected brothers. Both parents and an unaffected sister
      were heterozygous carriers. In addition, we identified two EIF2AK4 mutations in
      each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a
      family of kinases that regulate angiogenesis in response to cellular stress.
      CONCLUSIONS: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in
      familial and some nonfamilial cases.

PMID- 24135951
TI  - Numb cheek syndrome: a clinical-anatomical correlation. Diagnosis: Trigeminal
      schwannoma.

PMID- 24135948
TI  - Interdisciplinary European Guidelines on metabolic and bariatric surgery.
AB  - In 2012, an outstanding expert panel derived from IFSO-EC (International
      Federation for the Surgery of Obesity-European Chapter) and EASO (European
      Association for the Study of Obesity), composed by key representatives of both
      Societies including past and present presidents together with EASO's OMTF
      (Obesity Management Task Force) chair, agreed to devote the joint Medico-Surgical
      Workshop of both institutions to the topic of metabolic surgery as a pre
      satellite of the 2013 European Congress on Obesity (ECO) to be held in Liverpool
      given the extraordinarily advancement made specifically in this field during the
      past years. It was further agreed to revise and update the 2008 Interdisciplinary
      European Guidelines on Surgery of Severe Obesity produced in cooperation of both
      Societies by focusing in particular on the evidence gathered in relation to the
      effects on diabetes during this lustrum and the subsequent changes that have
      taken place in patient eligibility criteria. The expert panel composition allowed
      the coverage of key disciplines in the comprehensive management of obesity and
      obesity-associated diseases, aimed specifically at updating the clinical
      guidelines to reflect current knowledge, expertise and evidence-based data on
      metabolic and bariatric surgery.

PMID- 24135952
TI  - Viro-immunological response and emergence of resistance in HIV-infected women
      receiving combination antiretroviral regimens for the prevention of mother-to
      child transmission in Malawi.
AB  - OBJECTIVES: To identify factors associated with detectable viral load and the
      emergence of drug resistance in a cohort of HIV-infected pregnant women in Malawi
      receiving antiretroviral combination regimens for the prevention of mother-to
      infant transmission. METHODS: The study included 260 treatment-naive women who
      had received a three-drug nevirapine-based regimen from week 25 of gestational
      age until 6 months after delivery. HIV RNA was determined at month 6 and drug
      resistance was assessed if viral load was >50 copies/mL. Attendance at the
      scheduled follow-up visits was used as an indirect measure of treatment
      adherence. RESULTS: The rate of detectable HIV RNA at 6 months was 9.6% (25/260).
      The only significant predictor of this occurrence was the presence of >=1 missed
      visit during follow-up (P = 0.012). Resistance was assessed in 19 of these women:
      7 (37%) had a wild-type virus and the other 12 (63%) had resistance-associated
      mutations (nucleoside reverse transcriptase inhibitor, 7/12; non-nucleoside
      reverse transcriptase inhibitor, 11/12). Three of 12 cases (25%) in which
      mutations were detected had a viral load <1000 copies/mL. The emergence of
      resistance was not correlated with the presence of baseline mutations in either
      plasma or archived DNA. CONCLUSIONS: In this cohort of women, detectable HIV RNA
      6 months post-partum was infrequent and associated with low adherence to the
      treatment programme. Mutations were present in 63% of the women with detectable
      viral load at 6 months who had samples available for resistance testing. The
      impact of resistance on treatment re-initiation in women discontinuing drugs
      after the risk of transmission has ceased can be limited.

PMID- 24135953
TI  - Nitric oxide vs insulin secretion, action and clearance.

PMID- 24135955
TI  - The presence of air bronchogram is a novel predictor of negative nodal
      involvement in radiologically pure-solid lung cancer.
AB  - OBJECTIVES: Phase III trials regarding the feasibility of segmentectomy for lung
      cancer <= 2 cm in size are now underway in Japan and the USA. However, despite
      their small size, lung cancers that show a pure-solid appearance on thin-section
      computed tomography (CT) are considered to be invasive with a high frequency of
      nodal involvement. METHODS: Between 2008 and 2011, 556 clinical Stage IA lung
      cancer patients underwent pulmonary resection. For all patients, the findings
      obtained by preoperative thin-section CT were reviewed and the maximum
      standardized uptake value (SUVmax) on positron emission tomography was recorded.
      Several clinicopathological features were investigated to identify predictors of
      nodal metastasis using multivariate analyses. RESULTS: One hundred and eighty
      four clinical Stage IA lung cancer patients showed a pure-solid appearance on
      thin-section CT. Among them, air bronchogram was found radiologically in 58 (32%)
      patients. Nodal involvement was observed in 10 (17%) patients with air
      bronchogram, compared with 43 (34%) without air bronchogram, in clinical Stage IA
      pure-solid lung cancer. A multivariate analysis revealed that air bronchogram,
      clinical T1a and SUVmax were significant predictors of postoperative nodal
      involvement (P < 0.01, <0.01, and 0.03, respectively). Furthermore, nodal
      metastasis was never seen in patients with clinical T1a pure-solid lung cancers
      who had both air bronchogram and low SUVmax. CONCLUSIONS: The presence of air
      bronchogram was a novel predictor of negative nodal involvement in clinical Stage
      IA pure-solid lung cancer. Segmentectomy with thorough lymph node dissection is a
      feasible option for these patients despite a pure-solid appearance.

PMID- 24135954
TI  - Effect of heat stress and recovery on viability, oxidative damage, and heat shock
      protein expression in hepatic cells of grass carp (Ctenopharyngodon idellus).
AB  - In this study, we investigated the effects of hyperthermia and recovery on cell
      viability, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD)
      activity, malondialdehyde (MDA), total antioxidant capacity (T-AOC), and heat
      shock protein (HSP60, 70, and 90) mRNA expression in the hepatic cells of the
      grass carp, Ctenopharyngodon idellus. Triplicate groups of cultured cells were
      exposed to 30, 32, or 34  degrees C for 0.5 h and then immediately incubated at
      27  degrees C in 5 % CO2 for 6, 12, 24, or 48 h. Hyperthermia stress greatly
      reduced cell viability and increased LDH release. Cell damage declined after
      recovery. Hyperthermia stress increased the lipid peroxide levels and reduced the
      antioxidant capacity (e.g., reduced SOD and T-AOC) of the cells. However,
      oxidative damage declined as the recovery period increased, and the levels of
      MDA, SOD, and T-AOC were restored. After cells were exposed to 32  degrees C, the
      expression of HSP60 after recovery for 1, 2, and 4 h (P < 0.05), the expression
      of HSP70 after recovery for 0.5 and 1 h (P < 0.01), and the expression of HSP90
      throughout recovery were significantly higher (P < 0.01) than the prestress
      levels. During the recovery period, the variations in HSP gene expression
      reflected the transition period from a state of cellular growth to one of the
      cellular repairs. In conclusion, hyperthermia depresses cell viability, induces
      oxidative damage, and increases HSP expression, which plays an important role
      during hyperthermic stress in grass carp hepatic cells. 

PMID- 24135956
TI  - Heart transplantation with or without prior mechanical circulatory support in
      adults with congenital heart disease.
AB  - OBJECTIVES: Recent analyses establish that heart transplantation is increasing
      among adults with congenital heart disease (ACHD), but the effects of
      pretransplant mechanical circulatory support (MCS) on perioperative and post
      transplant outcomes have not been examined in the ACHD population. METHODS:
      Scientific Registry of Transplant Recipients data on all adult heart transplants
      from September 1987 to September 2012 (n = 47 160) were classified based on
      primary diagnosis codes as CHD or non-CHD and MCS or non-MCS. Demographic,
      procedural, outcome and survival variables were compared between MCS and non-MCS
      ACHD patient groups. RESULTS: MCS was used in 83 (6.8%) ACHD patients compared
      with 8625 (18.8%) patients without CHD (P < 0.001). MCS as a fraction of ACHD
      transplants increased over time (P = 0.002). MCS patients spent more time on the
      wait list, had a higher baseline serum creatinine and were more likely to be
      male, status 1A, hospitalized, in the ICU and/or on a ventilator prior to
      transplant. However, MCS patients experienced equivalent short-term survival (30
      day mortality = 10.8% in MCS vs 13.5% in non-MCS, P = 0.62) and overall survival
      by Kaplan-Meier analysis (P = 0.57). MCS patients had a longer post-transplant
      length of stay and were more likely to be transfused, but otherwise had no
      significant differences in adverse outcomes. CONCLUSIONS: MCS is less commonly
      used in adult CHD patients compared with all patients undergoing heart
      transplant, but has been increasing over time. Within the ACHD population,
      patients with MCS have a higher risk profile, but except for increased
      transfusion rate and longer length of stay, do not experience less favourable
      post-transplant outcomes.

PMID- 24135957
TI  - Live Dirofilaria immitis found during coronary artery bypass grafting procedure.
AB  - Dirofilaria immitis is a parasite transmitted by mosquito bites, where the most
      common primary hosts are dogs, cats and some wild animals. Humans become
      accidental hosts after being bitten by an infected mosquito and the number of
      such infections has rapidly increased during the last decade. We present a
      patient in which a live D. immitis has been found during myocardial
      revascularization. To the best of our knowledge, live D. immitis found in the
      substernal area during open heart surgery has never before been described. D.
      immitis in humans most often cause pulmonary nodules known as 'coin lesions'
      which are benign and asymptomatic, but it is very important for thoracic surgery
      that they are considered in the differential diagnosis of pulmonary nodules.
      Video assisted thoracic surgery has been proven as the best method for diagnosing
      and treating pulmonary dirofilariasis. 

PMID- 24135958
TI  - [Retinal vascular occlusions].

PMID- 24135959
TI  - [Endophthalmitis prophylaxis in intravitreal operative medication management
      administration(IVOM)].

PMID- 24135960
TI  - An efficient method for the Heck-Catellani reaction of aryl halides.
AB  - We describe herein a new method that allows selective production of Catellani
      Heck isomers from various aryl halides, including ones without ortho-groups.
      Under previous conditions, unhindered aryl halides were plagued with the
      formation of simple Heck isomers and multiple arylation and norbornene insertion.
      The use of a bulky PtBu3 ligand accelerates C-C reductive elimination from the
      key palladacycle. 

PMID- 24135961
TI  - The anatomy of a scientific rumor.
AB  - The announcement of the discovery of a Higgs boson-like particle at CERN will be
      remembered as one of the milestones of the scientific endeavor of the 21(st)
      century. In this paper we present a study of information spreading processes on
      Twitter before, during and after the announcement of the discovery of a new
      particle with the features of the elusive Higgs boson on 4(th) July 2012. We
      report evidence for non-trivial spatio-temporal patterns in user activities at
      individual and global level, such as tweeting, re-tweeting and replying to
      existing tweets. We provide a possible explanation for the observed time-varying
      dynamics of user activities during the spreading of this scientific "rumor". We
      model the information spreading in the corresponding network of individuals who
      posted a tweet related to the Higgs boson discovery. Finally, we show that we are
      able to reproduce the global behavior of about 500,000 individuals with
      remarkable accuracy. 

PMID- 24135962
TI  - The calcium release-activated calcium channel Orai1 represents a crucial
      component in hypertrophic compensation and the development of dilated
      cardiomyopathy.
AB  - As exceptionally calcium selective store-operated channels, Orai channels play a
      prominent role in cellular calcium signaling. While most studied in the immune
      system, we are beginning to recognize that Orai1 provides unique calcium
      signaling pathways in numerous tissue contexts. To assess the involvement of
      Orai1 in cardiac hypertrophy we used transverse aortic constriction to model
      pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice.
      We demonstrate that Orai1 deficient mice have significantly decreased survival in
      this pressure overload model. Transthoracic echocardiography reveals that Orai1
      deficient mice develop rapid dilated cardiomyopathy, with greater loss of
      function, and histological and molecular data indicate that this pathology is
      associated with significant apoptosis, but not major differences in cellular
      hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a
      crucial calcium entry mechanism in the compensation of the heart to pressure
      overload over-load, and the development of dilated cardiomyopathy.

PMID- 24135963
TI  - Characterization of the LCROSS impact plume from a ground-based imaging
      detection.
AB  - The Lunar CRater Observation and Sensing Satellite (LCROSS) mission was designed
      to search for evidence of water in a permanently shadowed region near the lunar
      south pole. An instrumented Shepherding Spacecraft followed a kinetic impactor
      and provided--from a nadir perspective--the only images of the debris plume. With
      independent observations of the visible debris plume from a more oblique view,
      the angles and velocities of the ejecta from this unique cratering experiment are
      better constrained. Here we report the first visible observations of the LCROSS
      ejecta plume from Earth, thereby ascertaining the morphology of the plume to
      contain a minimum of two separate components, placing limits on ejecta velocities
      at multiple angles, and permitting an independent estimate of the illuminated
      ejecta mass. Our mass estimate implies that the lunar volatile inventory in the
      Cabeus permanently shadowed region includes a water concentration of 6.3+/-1.6%
      by mass.

PMID- 24135965
TI  - The blood lactate increase in high intensity exercise is depressed by
      Acanthopanax sieboldianus.
AB  - This study investigates the anti-fatigue effects of Acanthopanax sieboldianus (A.
      sieboldianus) at various exercise intensities. Two experiments were conducted in
      18 Sprague-Dawley rats. In Experiment 1, a three-stage increment test (15 m/min
      for 5 min, and 20 m/min for 5 min and 25 m/min for 10 min) was performed using a
      treadmill. In Experiment 2, a 10-min swimming test was conducted. Blood samples
      were extracted from each rat before, during and after the exercises and the blood
      concentrations of lactate and glucose measured. In both experiments, water
      (control) or A. sieboldianus solution (ASS) was administered orally using a zonde
      30 min before the exercise. In the swimming test, ASS administration
      significantly decreased the blood lactate level measured at the end of the
      exercise and 5 min post-exercise relative to the water group, although the two
      groups did not differ significantly in the treadmill test. Our study demonstrates
      that a single oral administration of A. sieboldianus prior to high-intensity
      exercise significantly decreases the blood lactate concentration suggesting that
      A. sieboldianus has an intrinsic anti-fatigue effect. 

PMID- 24135964
TI  - Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in
      non-valvular atrial fibrillation: a cost-effectiveness analysis.
AB  - BACKGROUND AND OBJECTIVE: Non-valvular atrial fibrillation (NVAF) increases the
      risk of systemic thromboembolic events; therefore, anticoagulant treatment with
      vitamin K antagonists is widely prescribed. Recently, new oral anticoagulants
      (NOAs) directly inhibiting thrombin (dabigatran) or factor Xa (rivaroxaban and
      apixaban) demonstrated their non-inferiority with respect to warfarin in reducing
      the thromboembolic risk. The aim of this study was to estimate the cost
      effectiveness of NOAs in an Italian setting. METHODS: A Markov decision model
      including ten health states and death was developed, and a 3-month Markov cycle
      and lifetime horizon were adopted. Transition probabilities and quality of life
      were estimated from three randomized trials and from additional reports in the
      literature. Analysis was performed in the context of the Italian National Health
      System. First- and second-order sensitivity analyses were made to test the
      robustness of the results. The mean European cost of dabigatran (<euro>2.58/day)
      was assigned to each NOA. RESULTS: The incremental cost-utility ratio was below
      <euro>25,000/quality-adjusted life-year (QALY) gained for each NOA and each
      CHADS2 level, but differences among drugs were found. This result was sensitive
      to the time in (warfarin) therapeutic range and time horizon. CONCLUSIONS: Our
      analysis suggests that NOAs are a cost-effective treatment for the prevention of
      stroke in patients with NVAF in the Italian healthcare setting.

PMID- 24135966
TI  - The fate of tandemly duplicated genes assessed by the expression analysis of a
      group of Arabidopsis thaliana RING-H2 ubiquitin ligase genes of the ATL family.
AB  - Gene duplication events exert key functions on gene innovations during the
      evolution of the eukaryotic genomes. A large portion of the total gene content in
      plants arose from tandem duplications events, which often result in paralog genes
      with high sequence identity. Ubiquitin ligases or E3 enzymes are components of
      the ubiquitin proteasome system that function during the transfer of the
      ubiquitin molecule to the substrate. In plants, several E3s have expanded in
      their genomes as multigene families. To gain insight into the consequences of
      gene duplications on the expansion and diversification of E3s, we examined the
      evolutionary basis of a cluster of six genes, duplC-ATLs, which arose from
      segmental and tandem duplication events in Brassicaceae. The assessment of the
      expression suggested two patterns that are supported by lineage. While retention
      of expression domains was observed, an apparent absence or reduction of
      expression was also inferred. We found that two duplC-ATL genes underwent
      pseudogenization and that, in one case, gene expression is probably regained. Our
      findings provide insights into the evolution of gene families in plants, defining
      key events on the expansion of the Arabidopsis Toxicos en Levadura family of E3
      ligases. 

PMID- 24135967
TI  - A simple algorithm for subregional striatal uptake analysis with partial volume
      correction in dopaminergic PET imaging.
AB  - OBJECTIVE: In positron emission tomography (PET) of the dopaminergic system,
      quantitative measurements of nigrostriatal dopamine function are useful for
      differential diagnosis. A subregional analysis of striatal uptake enables the
      diagnostic performance to be more powerful. However, the partial volume effect
      (PVE) induces an underestimation of the true radioactivity concentration in small
      structures. This work proposes a simple algorithm for subregional analysis of
      striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging.
      METHODS: The PVC algorithm analyzes the separate striatal subregions and takes
      into account the PVE based on the recovery coefficient (RC). The RC is defined as
      the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration,
      and is derived from a combination of the traditional volume of interest (VOI)
      analysis and the large VOI technique. The clinical studies, comprising 11
      patients with Parkinson's disease (PD) and 6 healthy subjects, were used to
      assess the impact of PVC on the quantitative measurements. Simulations on a
      numerical phantom that mimicked realistic healthy and neurodegenerative
      situations were used to evaluate the performance of the proposed PVC algorithm.
      In both the clinical and the simulation studies, the striatal-to-occipital ratio
      (SOR) values for the entire striatum and its subregions were calculated with and
      without PVC. RESULTS: In the clinical studies, the SOR values in each structure
      (caudate, anterior putamen, posterior putamen, putamen, and striatum) were
      significantly higher by using PVC in contrast to those without. Among the PD
      patients, the SOR values in each structure and quantitative disease severity
      ratings were shown to be significantly related only when PVC was used. For the
      simulation studies, the average absolute percentage error of the SOR estimates
      before and after PVC were 22.74% and 1.54% in the healthy situation,
      respectively; those in the neurodegenerative situation were 20.69% and 2.51%,
      respectively. CONCLUSIONS: We successfully implemented a simple algorithm for
      subregional analysis of striatal uptake with PVC in dopaminergic PET imaging. The
      PVC algorithm provides an accurate measure of the SOR in the entire striatum and
      its subregions, and improves the correlation between the SOR values and the
      clinical disease severity of PD patients.

PMID- 24135968
TI  - Spectroscopic and mechanistic studies of dinuclear metallohydrolases and their
      biomimetic complexes.
AB  - An enhanced understanding of the metal ion binding and active site structural
      features of phosphoesterases such as the glycerophosphodiesterase from
      Enterobacter aerogenes (GpdQ), and the organophosphate degrading agent from
      Agrobacterium radiobacter (OpdA) have important consequences for potential
      applications. Coupled with investigations of the metalloenzymes, programs of
      study to synthesise and characterise model complexes based on these
      metalloenzymes can add to our understanding of structure and function of the
      enzymes themselves. This review summarises some of our work and illustrates the
      significance and contributions of model studies to knowledge in the area. 

PMID- 24135969
TI  - Intermittent Horner syndrome in a pediatric patient.
AB  - Intermittent Horner syndrome is uncommon in both the adult and pediatric
      population. We describe a case of a pediatric patient with an intermittent Horner
      syndrome. Infrared photography and videography were used to help establish the
      diagnosis.

PMID- 24135970
TI  - Patients with homonymous hemianopia become visually qualified to drive using
      novel monocular sector prisms.
AB  - Patients with homonymous hemianopia (HH) often fail to meet visual field (VF)
      requirements for a driver's license. We describe 2 patients with complete HH, who
      met the minimum VF requirements for driving using a novel, high-power, monocular
      sector prism system. Baseline VFs were assessed using automated and kinetic
      perimetry. Patients were fitted with glasses and press-on 57-PD peripheral
      monocular sector prisms placed on the lens ipsilateral to the VF defect above and
      below the visual axis with prisms oriented obliquely. Kinetic perimetry was
      reassessed both monocularly and binocularly, with and without prisms. The 2
      patients had 95 degrees  and 82 degrees  angle of continuous, horizontal,
      binocular VF. With the use of the prism system, the binocular VF increased to 115
      degrees  and 112 degrees  angles. Both patients reported improvement in quality
      of life and each holds a valid driver's license and has successfully operated a
      motor vehicle without any restrictions or accidents. These findings suggest that
      the addition of oblique 57-PD prisms to the ipsilateral spectacle lens above and
      below the visual axis for patients with complete HH can significantly increase
      horizontal VF, which may help an individual become visually qualified to obtain a
      driver's license.

PMID- 24135971
TI  - Point: does the risk of cross infection warrant exclusion of adults with cystic
      fibrosis from cystic fibrosis foundation events? Yes.

PMID- 24135972
TI  - UV-A emission from fluorescent energy-saving light bulbs alters local retinoic
      acid homeostasis.
AB  - Worldwide bans on incandescent light bulbs (ILBs) drive the use of compact
      fluorescent light (CFL) bulbs, which emit ultraviolet (UV) radiation. Potential
      health issues of these light sources have already been discussed, including
      speculation about the putative biological effects on light exposed tissues, yet
      the underlying mechanisms remain unclear. We hypothesized photoisomerization of
      all-trans retinoic acid (at-RA), a highly light sensitive morphogen, into
      biologically less active isomers, as a mechanism mediating biological effects of
      CFLs. Local at-RA is anti-carcinogenic, entrains molecular rhythms and is crucial
      for skin homeostasis. Therefore, we quantified the impact of CFL irradiation on
      extra- and intracellular levels of RA isomers using an epidermal cell culture
      model. Moreover, a biologically relevant impact of CFL irradiation was assessed
      using highly at-RA-sensitive human neuroblastoma cells. Dose-dependent conversion
      of extra- and intracellular at-RA into the biologically less active 13-cis-isomer
      was significantly higher in CFL vs. ILB exposure and completely preventable by
      employing a UV-filter. Moreover, pre-irradiation of culture media by CFL
      attenuated at-RA-specific effects on cell viability in human at-RA-sensitive
      cells in a dose-dependent manner. These findings point towards a biological
      relevance of CFL-induced at-RA decomposition, providing a mechanism for CFL
      mediated effects on environmental health. 

PMID- 24135973
TI  - Effectiveness of a low-calorie weight loss program in moderately and severely
      obese patients.
AB  - AIMS: To compare effectiveness of a 1-year weight loss program in moderately and
      severely obese patients. METHODS: The study sample included 311 obese patients
      participating in a weight loss program, which comprised a 12-week weight
      reduction phase (low-calorie formula diet) and a 40-week weight maintenance
      phase. Body weight and glucose and lipid values were determined at the beginning
      of the program as well as after the weight reduction and the weight maintenance
      phase. Participants were analyzed according to their BMI class at baseline (30
      34.9 kg/m2; 35-39.9 kg/m2; 40-44.9 kg/m2; 45-49.9 kg/m2; >=50 kg/m2).
      Furthermore, moderately obese patients (BMI < 40 kg/m2) were compared to severely
      obese participants (BMI >= 40 kg/m2). RESULTS: Out of 311 participants, 217
      individuals completed the program. Their mean baseline BMI was 41.8 +/- 0.5
      kg/m2. Average weight loss was 17.9 +/- 0.6%, resulting in a BMI of 34.3 +/- 0.4
      kg/m2 after 1 year (p < 0.001). Overall weight loss was not significantly
      different in moderately and severely obese participants. Yet, severely obese
      participants achieved greater weight loss during the weight maintenance phase
      than moderately obese participants (-3.1 +/- 0.7% vs. -1.2 +/- 0.6%; p = 0.04).
      Improvements in lipid profiles and glucose metabolism were found throughout all
      BMI classes. CONCLUSION: 1-year weight loss intervention improves body weight as
      well as lipid and glucose metabolism not only in moderately, but also in severely
      obese individuals.

PMID- 24135974
TI  - Slowly contracting muscles power the rapid jumping of planthopper insects
      (Hemiptera, Issidae).
AB  - The planthopper insect Issus produces one of the fastest and most powerful jumps
      of any insect. The jump is powered by large muscles that are found in its thorax
      and that, in other insects, contribute to both flying and walking movements.
      These muscles were therefore analysed by transmission electron microscopy to
      determine whether they have the properties of fast-acting muscle used in flying
      or those of more slowly acting muscle used in walking. The muscle fibres are
      arranged in a parallel bundle that inserts onto an umbrella-shaped tendon. The
      individual fibres have a diameter of about 70 MUm and are subdivided into
      myofibrils a few micrometres in diameter. No variation in ultrastructure was
      observed in various fibres taken from different parts of the muscle. The
      sarcomeres are about 15 MUm long and the A bands about 10 MUm long. The Z lines
      are poorly aligned within a myofibril. Mitochondrial profiles are sparse and are
      close to the Z lines. Each thick filament is surrounded by 10-12 thin filaments
      and the registration of these arrays of filaments is irregular. Synaptic boutons
      from the two excitatory motor neurons to the muscle fibres are characterised by
      accumulations of ~60 translucent 40-nm-diameter vesicle profiles per section,
      corresponding to an estimated 220 vesicles, within a 0.5-MUm hemisphere at a
      presynaptic density. All ultrastructural features conform to those of slow muscle
      and thus suggest that the muscle is capable of slow sustained contractions in
      keeping with its known actions during jumping. A fast and powerful movement is
      thus generated by a slow muscle. 

PMID- 24135975
TI  - Multi-colour nanowire photonic crystal laser pixels.
AB  - Emerging applications such as solid-state lighting and display technologies
      require micro-scale vertically emitting lasers with controllable distinct lasing
      wavelengths and broad wavelength tunability arranged in desired geometrical
      patterns to form "super-pixels". Conventional edge-emitting lasers and current
      surface-emitting lasers that require abrupt changes in semiconductor bandgaps or
      cavity length are not a viable solution. Here, we successfully address these
      challenges by introducing a new paradigm that extends the laser tuning range
      additively by employing multiple monolithically grown gain sections each with a
      different emission centre wavelength. We demonstrate this using broad gain
      bandwidth III-nitride multiple quantum well (MQW) heterostructures and a novel
      top-down nanowire photonic crystal nanofabrication. We obtain single-mode lasing
      in the blue-violet spectral region with a remarkable 60 nm of tuning (or 16% of
      the nominal centre wavelength) that is determined purely by the photonic crystal
      geometry. This approach can be extended to cover the entire visible spectrum. 

PMID- 24135976
TI  - The effect of the physical state of binders on high-shear wet granulation and
      granule properties: a mechanistic approach to understand the high-shear wet
      granulation process. part IV. the impact of rheological state and tip-speeds.
AB  - The purpose of this study is to provide a mechanistic understanding concerning
      the effect of tip-speed on a granulation at various binder rheological states;
      the in situ rheological state of a binder was controlled by exposing a
      granulation blend to 96% relative humidity. This approach allowed us to
      investigate the impact of tip-speed on granule consolidation coupled with the in
      situ binder state, which was not possible using a conventional granulation
      approach. Experimentally, the rheological state of binders was characterized
      using a rheometer. Granule size and granule porosity were measured by Qicpic
      instrument and Mercury Intrusion Porosimetry, respectively. For the granulations
      containing binders at viscous state (PVP K17 and PVP K29/32), the granule size
      increased significantly with mixing time and the growth rate increased with tip
      speed until 5.8 m/s; when binders were at viscoelastic state, tip-speed had no
      impact on granulation. Furthermore, the granule porosity was higher for
      granulation with binders at viscoelastic state (HPC and PVP K90), whereas it was
      lower for granulation with binders at viscous state. In addition, the impeller
      tip-speed had minimal impact on the porosity of the final granules. Finally,
      Ennis' model was used for interpreting results, providing mechanistic insights on
      granulation.

PMID- 24135977
TI  - A pioneer in the field of autophagy microscopy: Attila L Kovacs.

PMID- 24135978
TI  - General combining ability of most yield-related traits had a genetic basis
      different from their corresponding traits per se in a set of maize introgression
      lines.
AB  - Evaluation of combining ability is a crucial process in hybrid breeding, and
      dissection of the genetic basis of combining ability will facilitate hybrid
      breeding. In this study, molecular markers significantly associated with general
      combining ability (GCA) of seven yield-related traits and the traits per se were
      detected in a set of maize introgression lines (ILs) under three environments.
      Totally 25 and 31 significant loci for GCA and the traits per se were commonly
      detected under multiple environments, respectively. Correlation analysis and
      comparison among these significant loci revealed that the genetic basis of GCA of
      these yield-related traits was generally different from that of the traits per se
      except for the trait of ear row number. In addition, GCA of the ILs was
      positively and significantly correlated to the total relative effects of
      significant GCA loci in the ILs in general, implying that the GCA loci identified
      in this study would be useful in molecular breeding. Correlation analysis also
      showed that the GCA of yield per plant was strongly correlated to the GCA of
      kernel number per row, ear length and 100-kernel-weight, thus these traits were
      more important in genetic improvement for GCA. Results in this study would
      provide useful information for hybrid breeding in maize. 

PMID- 24135979
TI  - Prebiotic oligosaccharides in premature infants.
AB  - OBJECTIVE: The aim of the study was to determine the impact of increasing doses
      of 2 prebiotic oligosaccharides and of an "all-human diet" on the intestinal
      microbiota of premature infants. METHODS: Twelve premature infants receiving
      formula feedings were randomly assigned to receive either galacto-oligosaccharide
      (F+GOS) or a pooled concentrated donor human milk product containing human milk
      oligosaccharides (F+HMO) in increasing doses during a 5-week period. A second
      group of 15 premature infants received their mother's own milk fortified with
      either a concentrated donor human milk product (H+H) or a bovine powdered
      fortifier (H+B). Serial stool specimens from each infant were analyzed by
      terminal restriction fragment length polymorphism and quantitative polymerase
      chain reaction for bacterial composition. RESULTS: All of the infants studied had
      relatively low levels of bifidobacteria and no measurable Lactobacilli. Infants
      from the F+GOS and F+HMO groups demonstrated an increase in relative numbers of
      Clostridia with increasing doses. Compared with the H+B group, the infants in the
      F+HMO and the H+H groups showed an unexpected trend toward an increase in gamma
      Proteobacteria over time/dose. Principal coordinate analyses and Shannon
      diversity scores were not significantly different among the 4 groups. Infants in
      the H+H group received more antibiotics during the study period than those in the
      other groups. Two of the infants receiving GOS developed feeding intolerance.
      CONCLUSIONS: None of the prebiotic interventions resulted in significant
      increases in bifidobacteria compared with baseline specimens or the H+B group;
      however, many of the infants did not receive the highest doses of GOS and HMO,
      and antibiotic use in the H+H group was high.

PMID- 24135980
TI  - Development and validation of a pediatric IBD knowledge inventory device: the IBD
      KID.
AB  - OBJECTIVES: Questionnaires exist to assess inflammatory bowel disease (IBD)
      related knowledge of adults. Owing to wording and content concerns, these were
      believed to be inappropriate for use in pediatric patients. The aim of this study
      was to develop a questionnaire to assess disease-related knowledge of pediatric
      patients with IBD and their parents. METHODS: Following a formal process of item
      generation and reduction, the IBD-Knowledge Inventory Device was developed and
      pilot tested. It was administered to 10- to 17-year-old patients with IBD, and to
      1 of each of their parents. To evaluate its discriminatory validity, pediatric
      residents, nurses, and ward clerks completed the questionnaire. RESULTS: A total
      of 99 patients (mean 42, Crohn disease 46, age 14(+/-2) years) and 99 parents
      completed the IBD-Knowledge Inventory Device. Parent knowledge scores, 15(+/-4),
      were higher than those of patients, 11(+/-4), P < 0.001. Patient and parent
      knowledge scores were strongly correlated (r = 0.62, P < 0.001). Patient
      knowledge score was significantly related to disease type (Crohn disease scored
      higher than ulcerative colitis, P = 0.004) and to perceived knowledge level (P <
      0.001) by regression analysis. Similarly, parent knowledge score was
      significantly related to sex (girls scored higher, P = 0.014), postsecondary
      education (P < 0.001), and perceived knowledge level (P = 0.002). The
      questionnaire scores of 23 were 19, 16, and 10, respectively, for residents,
      nurses, and ward clerks. Both residents and nurses scored significantly higher
      than ward clerks (P = 0.001 for both). CONCLUSIONS: A valid IBD-related knowledge
      assessment questionnaire was developed for use in older children and adolescents
      with IBD and their parents.

PMID- 24135981
TI  - Pediatric endoscopic gastrostomy tubes: outcomes that guide decision making.

PMID- 24135982
TI  - Rectal motility in pediatric constipation.
AB  - OBJECTIVES: Constipation is a common disorder in children, but little is known
      about its etiology. Rectal impedance planimetry determines segmental rectal cross
      sectional area (CSA) and pressure, allowing detailed description of rectal
      motility. The aim of the present study was to compare rectal motility in healthy
      and constipated children. METHODS: We analyzed data from 10 children (1 girl)
      with constipation according to the Rome III criteria, mean age 8.8 years
      (standard deviation +/- 1.2), and 10 healthy children (5 girls), mean age 9.9
      years (standard deviation +/- 1.5). CSA was determined at 3 levels (4, 5.5, and 7
      cm from the anal verge). The resting rectal motility was recorded for 30 minutes
      followed by a distension protocol to assess compliance. Runs of phasic rectal
      contractions were defined as changes of >10% from baseline CSA and lasting at
      least 2 minutes. Rectal dimensions were expressed as mean CSA. RESULTS: A low
      amplitude contraction pattern (3%-5% of baseline CSA) with a frequency of 6 to
      8/minute was present in all of the children. There was significantly more time
      with phasic rectal contractions in constipated children (median 38%, range [0
      100]) compared with healthy children (median 8.8%, range [0-57]) (P < 0.05). The
      rectal CSA was higher in constipated children (median 1802 mm [range 1106-2948])
      compared with healthy children (1375 mm [range 437-1861]) (P < 0.05), but
      compliance did not differ (constipated: median 38 mm/H2O [range 12-86] vs healthy
      33 mm/H2O [range 10-63]) (P = 30). CONCLUSIONS: In children with constipation, we
      found phasic rectal contractions for a significantly longer period compared with
      healthy children, and their rectum is larger than normal.

PMID- 24135983
TI  - Iron requirements of infants and toddlers.
AB  - Iron deficiency (ID) is the most common micronutrient deficiency worldwide and
      young children are a special risk group because their rapid growth leads to high
      iron requirements. Risk factors associated with a higher prevalence of ID anemia
      (IDA) include low birth weight, high cow's-milk intake, low intake of iron-rich
      complementary foods, low socioeconomic status, and immigrant status. The aim of
      this position paper was to review the field and provide recommendations regarding
      iron requirements in infants and toddlers, including those of moderately or
      marginally low birth weight. There is no evidence that iron supplementation of
      pregnant women improves iron status in their offspring in a European setting.
      Delayed cord clamping reduces the risk of ID. There is insufficient evidence to
      support general iron supplementation of healthy European infants and toddlers of
      normal birth weight. Formula-fed infants up to 6 months of age should receive
      iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6-1.2 mg(
      1) . kg(-1) . day(-1)). Marginally low-birth-weight infants (2000-2500 g) should
      receive iron supplements of 1-2 mg(-1) . kg(-1) . day(-1). Follow-on formulas
      should be iron-fortified; however, there is not enough evidence to determine the
      optimal iron concentration in follow-on formula. From the age of 6 months, all
      infants and toddlers should receive iron-rich (complementary) foods, including
      meat products and/or iron-fortified foods. Unmodified cow's milk should not be
      fed as the main milk drink to infants before the age of 12 months and intake
      should be limited to <500 mL/day in toddlers. It is important to ensure that this
      dietary advice reaches high-risk groups such as socioeconomically disadvantaged
      families and immigrant families.

PMID- 24135984
TI  - Incidence and phenotypic characteristics of pediatric IBD in northeastern
      Slovenia, 2002-2010.
AB  - OBJECTIVES: The purpose of the present study was to determine the incidence of
      inflammatory bowel disease (IBD) and its subgroups in children in northeastern
      Slovenia (NE Slovenia) during the period 2002-2010, and to assess the phenotypic
      characteristics at the diagnosis and during the follow-up. METHODS: A
      retrospective investigation was conducted on a cohort of newly diagnosed children
      and adolescents with IBD ages 0 to 18 years between 2002 and 2010 and residing in
      NE Slovenia. The phenotypic characteristics were determined at presentation and
      during follow-up. The location of Crohn disease (CD) and ulcerative colitis (UC)
      was assessed according to the Paris classification at diagnosis, and later in
      patients who had a follow-up period >2 years. The type of therapy at diagnosis
      and during follow-up, and the need for surgery were determined. The study covered
      approximately one-third of the total pediatric population (0-18 years). RESULTS:
      In total, 107 cases of IBD were diagnosed during the study period. The mean
      annual incidence (per 100,000) was 7.6 (95% confidence interval [CI] 6.3-9.2) for
      all IBD, 4.6 (95% CI 3.6-5.9) for CD, and 2.8 (95% CI 1.9-3.8) for UC. The
      incidences of total IBD, CD, and UC increased from 5.7 (3.8-8.2), 3.9 (2.3-6.1),
      and 1.8 (0.8-3.5) in the period 2002-2004, respectively, to 8.9 (6.3-12.2), 5.0
      (3.1-7.6), and 3.4 (1.9-5.6) in the period 2008-2010, respectively. During the
      follow-up, the proportion of complicated CD disease behavior
      (stricturing/penetrating) had doubled. A total of 18.5% of patients with CD
      underwent bowel surgery. CONCLUSIONS: The incidence of childhood IBD in the
      northeastern part of the country is high and comparable with that reported from
      the developed western countries of Europe, and is probably still increasing. This
      increase may be the result of changes in the lifestyle, especially in dietary
      habits during the last 20 years.

PMID- 24135986
TI  - WITHDRAWN: Supplemental perioperative steroids for surgical patients with adrenal
      insufficiency.

PMID- 24135987
TI  - Clinical application of mucosal valve technique for anastomosis during
      esophagogastrostomy.
AB  - BACKGROUND: The study aims to compare the efficacy in prevention of anastomotic
      complications using layer-to-layer mucosal valve technique versus circular
      stapled technique for esophagogastric intrathoracic anastomosis after resection
      for esophageal and gastric cardiac carcinoma. METHODS: From January 2005 to
      December 2010, 136 patients received layer-to-layer mucosal valve technique (LM
      group), 219 received circular stapled anastomosis (CS group) after curative
      intent resection for esophageal and gastric cardiac carcinoma. The technique
      details were reported and the clinical results were analyzed. RESULTS: The two
      groups were comparable on clinical baseline characteristics. The average duration
      of operation was longer with LM technique by 16 min, but without statistical
      significance (P = 0.073). There was no anastomotic leakage in the LM group, while
      in the CS group, leakage occurred in seven patients (3.2 %, P = 0.047). Both the
      incidence and grade of postoperative dysphagia were significantly lower in the LM
      group (P < 0.05). Significantly fewer patients experienced stricture after LM
      technique (3.8 %) compared with CS anastomosis (18.2 %, P < 0.001). CS
      anastomosis was associated with a significantly higher incidence of persistent
      stricture requiring more dilatation (P < 0.001). Symptoms of reflux were better
      controlled by LM technique; 82.7 % of patients were asymptomatic with respect to
      reflux compared to 58.9 % in the CS group, P < 0.001. And there was a significant
      reduction in the incidence of esophagitis in remnant esophagus in the LM group (P
      = 0.001). CONCLUSIONS: The layered mucosal valve anastomosis could significantly
      diminish the incidence of anastomotic complications and could be used as an
      alternative for esophagogastric anastomosis after resection of esophageal and
      gastric cardiac carcinoma.

PMID- 24135989
TI  - Real-time label-free surface plasmon resonance biosensing with gold nanohole
      arrays fabricated by nanoimprint lithography.
AB  - In this work we present a surface plasmon resonance sensor based on enhanced
      optical transmission through sub-wavelength nanohole arrays. This technique is
      extremely sensitive to changes in the refractive index of the surrounding medium
      which result in a modulation of the transmitted light. The periodic gold nanohole
      array sensors were fabricated by high-throughput thermal nanoimprint lithography.
      Square periodic arrays with sub-wavelength hole diameters were obtained and
      characterized. Using solutions with known refractive index, the array
      sensitivities were obtained. Finally, protein absorption was monitored in real
      time demonstrating the label-free biosensing capabilities of the fabricated
      devices. 

PMID- 24135988
TI  - Exposure-toxicity relationship of sorafenib in Japanese patients with renal cell
      carcinoma and hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Sorafenib has various adverse events that can cause
      treatment discontinuation or dose reduction. The aim of this study was to compare
      the safety profile between renal cell carcinoma (RCC) and hepatocellular
      carcinoma (HCC) patients receiving sorafenib under real-life practice conditions.
      Furthermore, we investigated the relationship between sorafenib exposure and
      clinical outcomes. METHODS: A total of 91 Japanese cancer patients (RCC, n = 21;
      HCC, n = 70) treated with sorafenib were enrolled. Toxicity was graded according
      to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI
      CTCAE) version 4.0. Single blood samples were collected at each clinic visit and
      serum sorafenib concentrations were measured by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The incidence of adverse events was analyzed according
      to cancer type and sorafenib concentration. RESULTS: Hand-foot skin reaction
      (HFSR) was the most common adverse event among RCC (76 %) and HCC (66 %)
      patients. Elevations in hepatic transaminases and pancreatic amylase developed
      more frequently in patients with RCC than in those with HCC (p < 0.05), while
      hyperbilirubinemia and thrombocytopenia were observed more often in HCC patients
      than in RCC patients (p < 0.05). Pharmacokinetic data were available from 52
      patients (RCC, n = 16; HCC, n = 36). HCC patients showed significantly higher
      dose-normalized concentrations than RCC patients (p = 0.0184). Sorafenib
      concentrations were significantly greater in patients with grade >=2 HFSR and
      hypertension than in those not experiencing the adverse events (p = 0.0045 and
      0.0453, respectively). Furthermore, receiver operating characteristic curves
      revealed optimal cutoff concentrations of sorafenib to predict grade >=2 HFSR
      (5.78 MUg/mL) and hypertension (4.78 MUg/mL). In addition, a trend of prolonged
      overall survival was observed in HCC patients who achieved a maximal sorafenib
      concentration of >=4.78 MUg/mL during treatment compared with those who did not
      achieve the threshold concentration (12.0 vs. 6.5 months; log-rank p = 0.0824).
      CONCLUSIONS: The results of this study suggest that the safety and
      pharmacokinetic profiles of sorafenib differ between Japanese cancer patients
      with RCC and HCC. Furthermore, the serum sorafenib concentration could be used as
      a guide to avoiding the development of severe HFSR while allowing prediction of
      the incidence of grade >=2 hypertension in patients with RCC and HCC, and may
      potentially be related to the clinical efficacy of sorafenib for HCC.

PMID- 24135990
TI  - Identification of volatiles produced by Cladosporium cladosporioides CL-1, a
      fungal biocontrol agent that promotes plant growth.
AB  - Certain microbial Volatile Organic Compounds (VOCs) have been reported to enhance
      the growth and development of plants. The biocontrol fungi, Cladosporium
      cladosporioides CL-1 significantly improved the growth of tobacco seedlings in
      vitro when they were co-cultivated without physical contact. SPME Quadrupole
      GC/MS/MS revealed that CL-1 emited the volatiles alpha-pinene, (-)-trans
      caryophyllene, tetrahydro-2,2,5,5-tetramethylfuran, dehydroaromadendrene, and (+)
      sativene. Potential roles of these volatiles in plant growth and development are
      discussed. Even though there were several fungal VOCs reported in the past that
      could influence plant growth, their exact mechanisms of action are not fully
      known. Fungal VOC-mediated plant growth promotion requires in-depth study in
      order for this technology to be used in large scale for crops, especially those
      grown under greenhouse conditions. 

PMID- 24135991
TI  - Accelerometer-based event detector for low-power applications.
AB  - In this paper, an adaptive, autocovariance-based event detection algorithm is
      proposed, which can be used with micro-electro-mechanical systems (MEMS)
      accelerometer sensors to build inexpensive and power efficient event detectors.
      The algorithm works well with low signal-to-noise ratio input signals, and its
      computational complexity is very low, allowing its utilization on inexpensive low
      end embedded sensor devices. The proposed algorithm decreases its energy
      consumption by lowering its duty cycle, as much as the event to be detected
      allows it. The performance of the algorithm is tested and compared to the
      conventional filter-based approach. The comparison was performed in an
      application where illegal entering of vehicles into restricted areas was
      detected. 

PMID- 24135992
TI  - Dynamic task allocation in multi-hop multimedia wireless sensor networks with low
      mobility.
AB  - This paper presents a task allocation-oriented framework to enable efficient in
      network processing and cost-effective multi-hop resource sharing for dynamic
      multi-hop multimedia wireless sensor networks with low node mobility, e.g.,
      pedestrian speeds. The proposed system incorporates a fast task reallocation
      algorithm to quickly recover from possible network service disruptions, such as
      node or link failures. An evolutional self-learning mechanism based on a genetic
      algorithm continuously adapts the system parameters in order to meet the desired
      application delay requirements, while also achieving a sufficiently long network
      lifetime. Since the algorithm runtime incurs considerable time delay while
      updating task assignments, we introduce an adaptive window size to limit the
      delay periods and ensure an up-to-date solution based on node mobility patterns
      and device processing capabilities. To the best of our knowledge, this is the
      first study that yields multi-objective task allocation in a mobile multi-hop
      wireless environment under dynamic conditions. Simulations are performed in
      various settings, and the results show considerable performance improvement in
      extending network lifetime compared to heuristic mechanisms. Furthermore, the
      proposed framework provides noticeable reduction in the frequency of missing
      application deadlines. 

PMID- 24135993
TI  - Simultaneous determination of dopamine, sertonin and ascorbic acid at a glassy
      carbon electrode modified with carbon-spheres.
AB  - A novel glassy carbon electrode (GCE) modified with carbon-spheres has been
      fabricated through a simple casting procedure. The modified GCE displays high
      selectivity and excellent electrochemical catalytic activities towards dopamine
      (DA), serotonin (5-HT), and ascorbic acid (AA). In the co-existence system, the
      peak separations between AA and DA, DA and 5-HT, and AA and 5-HT are large up to
      230, 180, and 410 mV, respectively. Differential pulse voltammetry (DPV) has been
      employed to simultaneously detect DA, 5-HT, and AA, and the linear calibration
      curves for DA, 5-HT, and AA are obtained in the range of 20.0-150.0 MUM, 40.0
      750.0 MUM and 300.0-2,000.0 MUM with detection limits (S/N = 3) of 2.0 MUM, 0.7
      MUM and 0.6 MUM, respectively. The proposed electrode has been applied to detect
      DA, 5-HT, and AA in real samples using standard addition method with satisfactory
      results. 

PMID- 24135994
TI  - Water can stably disperse liquid-exfoliated graphene.
AB  - Liquid-exfoliated graphene can be stably dispersed in water and concurrently
      maintain its high quality (average 1 nm thick, low content of defects and
      oxides). The high stability is attributed to the reduction of flake size and thus
      the enhanced edge effects. This work opens up a whole new vista on how to
      disperse graphene. 

PMID- 24135995
TI  - Macrophyte disturbance alters aquatic surface microlayer structure, metabolism,
      and fate.
AB  - Macrophytes drive the functioning of many salt marsh ecosystem components. We
      questioned how temporary clearing of the macrophyte community, during
      restoration, would impact processes at the scale of the aquatic surface
      microlayer. Development, deposition, and breakup of the tidal creek surface
      microlayer were followed over tidal cycles seasonally in a cleared "former"
      Phragmites marsh and an adjacent restored Spartina marsh. Metabolic and physical
      processes of the mobile surface microlayers and underlying water were compared,
      along with distribution of organic and inorganic components onto simulated plant
      stems. In July and October, chlorophyll-a quantities were less on simulated stems
      in the cleared site than in the restored site. The aquatic microlayer in the
      cleared site creek exhibited lower photosynthesis and respiration rates, fewer
      diatoms and green algae, and less chlorophyll-a. There was a lower concentration
      (250 times) and reduced diversity of fatty acids in the surface microlayer of the
      cleared site, reflecting a smaller and less diverse microbial community and
      reduced food resources. Fiddler crab activity was an order of magnitude higher
      where macrophytes had been cleared. Their consumption of edaphic algae on the mud
      surface may account for the reduced algae and other organics in the creek surface
      microlayer, thus representing a redirection of this food resource from creek
      consumers. Overall, there were less total particulates in the creek surface
      microlayer at the cleared site, and they dropped out of the surface microlayer
      sooner in the tidal cycle, resulting in a lower sediment load available for
      deposit onto marsh surfaces. 

PMID- 24135996
TI  - Heavy rainfall increases nestling mortality of an Arctic top predator:
      experimental evidence and long-term trend in peregrine falcons.
AB  - Although animal population dynamics have often been correlated with fluctuations
      in precipitation, causal relationships have rarely been demonstrated in wild
      birds. We combined nest observations with a field experiment to investigate the
      direct effect of rainfall on survival of peregrine falcon (Falco peregrinus)
      nestlings in the Canadian Arctic. We then used historical data to evaluate if
      recent changes in the precipitation regime could explain the long-term decline of
      falcon annual productivity. Rainfall directly caused more than one-third of the
      recorded nestling mortalities. Juveniles were especially affected by heavy
      rainstorms (>=8 mm/day). Nestlings sheltered from rainfall by a nest box had
      significantly higher survival rates. We found that the increase in the frequency
      of heavy rain over the last three decades is likely an important factor
      explaining the recent decline in falcon nestling survival rates, and hence the
      decrease in annual breeding productivity of the population. Our study is among
      the first experimental demonstrations of the direct link between rainfall and
      survival in wild birds, and clearly indicates that top arctic predators can be
      significantly impacted by changes in precipitation regime.

PMID- 24135997
TI  - State-transitions facilitate robust quantum yields and cause an over-estimation
      of electron transport in Dunaliella tertiolecta cells held at the CO2
      compensation point and re-supplied with DIC.
AB  - Photosynthetic energy consumption and non-photosynthetic energy quenching
      processes are inherently linked. Both processes must be controlled by the cell to
      allow cell maintenance and growth, but also to avoid photodamage. We used the
      chlorophyte algae Dunaliella tertiolecta to investigate how the interactive
      regulation of photosynthetic and non-photosynthetic pathways varies along
      dissolved inorganic carbon (DIC) and photon flux gradients. Specifically, cells
      were transferred to DIC-deplete media to reach a CO2 compensation before being re
      supplied with DIC at various concentrations and different photon flux levels.
      Throughout these experiments we monitored and characterized the
      photophysiological responses using pulse amplitude modulated fluorescence, oxygen
      evolution, 77 K fluorescence emission spectra, and fast-repetition rate
      fluorometry. O2 uptake was not significantly stimulated at DIC depletion, which
      suggests that O2 production rates correspond to assimilatory photosynthesis.
      Fluorescence-based measures of relative electron transport rates (rETRs) over
      estimated oxygen-based photosynthetic measures due to a strong state-transitional
      response that facilitated high effective quantum yields. Adoption of an
      alternative fluorescence-based rETR calculation that accounts for state
      transitions resulted in improved linear oxygen versus rETR correlation. This
      study shows the extraordinary capacity of D. tertiolecta to maintain stable
      effective quantum yields by flexible regulation of state-transitions.
      Uncertainties about the control mechanisms of state-transitions are presented.

PMID- 24135999
TI  - Counterpoint: does the risk of cross infection warrant exclusion of adults with
      cystic fibrosis from cystic fibrosis foundation events? No.

PMID- 24136000
TI  - Community attitudes and social distance towards the mentally ill in South Sudan:
      a survey from a post-conflict setting with no mental health services.
AB  - PURPOSE: This study investigates attitudes and social distance towards the
      mentally ill in a post-conflict, low-income country. METHODS: A cross-sectional
      community survey (n = 1,200) was conducted in South Sudan. Associations between
      various sociodemographic variables and attitudes toward/social distance from the
      mentally ill were investigated. RESULTS: The regression analysis showed that
      lower levels of education were positively associated with social distance, and
      Christian or Muslim beliefs, compared with traditional beliefs, were negatively
      associated with social distance. Familiarity with mental illness or psychological
      distress was not significantly associated with social distance. Participants who
      endorsed community-oriented attitudes (rather than hospital/drug-oriented
      attitudes) about health care for the mentally ill were more likely show a
      decreased social distance. Participants who believed that the mentally ill were
      dangerous had higher scores on the social distance scale. CONCLUSIONS: A high
      level of stigma towards the mentally ill exists in South Sudan, especially in the
      rural areas. Alongside efforts to build up mental health services in South Sudan,
      the existing stigma needs to be addressed. Information regarding the role of the
      community both in preventing mental illnesses and in service delivery should be
      prioritised.

PMID- 24135998
TI  - Inborn errors of the development of human natural killer cells.
AB  - PURPOSE OF REVIEW: Inborn errors of human natural killer (NK) cells may affect
      the development of these cells, their function, or both. There are two broad
      categories of genetic defects of NK cell development, depending on whether the
      deficiency is apparently specific to NK cells or clearly affects multiple
      hematopoietic lineages. We review here recent progress in the genetic dissection
      of these NK deficiencies (NKDs). RECENT FINDINGS: Patients with severe combined
      immunodeficiencies bearing mutations of adenosine deaminase, adenylate kinase 2,
      interleukin-2 receptor gamma chain, and Janus kinase 3 genes present NKDs and are
      prone to a broad range of infections. Patients with GATA binding protein 2
      deficiency are susceptible to both mycobacterial and viral infections, and
      display NKDs and a lack of monocytes. Rare patients with mini chromosomal
      maintenance 4 deficiency display an apparently selective NKD associated with
      viral infections, but they also display various nonhematopoietic phenotypes,
      including adrenal insufficiency and growth retardation. SUMMARY: These studies
      have initiated a genetic dissection of the development of human NK cells. Further
      studies are warranted, including the search for genetic causes of NKD in
      particular. This research may lead to the discovery of molecules specifically
      controlling the development of NK cells and to improvements in our understanding
      of the hitherto elusive function of these cells in humans.

PMID- 24136001
TI  - The motivation paradox: higher psychosocial problem levels in severely mentally
      ill patients are associated with less motivation for treatment.
AB  - PURPOSE: Lack of motivation for treatment makes a subgroup of patients with
      severe mental illness (SMI) difficult to engage in psychiatric treatment. Such
      difficult-to-engage patients may also be the most in need of treatment. We
      hypothesized that the level of psychosocial problems would be inversely related
      to motivation for treatment. METHODS: Cross-sectional study in two independent
      samples. The first sample (n = 294) included SMI patients who participated in a
      randomized controlled trial and were assessed using the Health of the Nation
      Outcome Scales (HoNOS) and self-rated and clinician-rated motivation-for
      treatment scales. The second sample (n = 1,170) included SMI patients who were
      treated in Assertive Outreach Teams and were routinely assessed with the HoNOS
      and a motivation-for-treatment scale. In both samples, patients also self-rated
      their quality of life. RESULTS: In both samples, patients with HoNOS scores of 16
      and higher had lower motivation scores on all motivation scales than patients
      with lower HoNOS scores, and also a lower quality of life. CONCLUSIONS: A
      motivation paradox seems inherent to this association between higher psychosocial
      problems levels, less motivation for treatment, and lower quality of life. Such a
      paradox has clinical relevance, as it may provide an ethical basis for outreach
      services which aim to engage marginally motivated SMI patients with severe
      psychosocial problems into mental health care.

PMID- 24136003
TI  - Ferrocene-based multichannel ion-pair recognition receptors.
AB  - Ferrocenylimidazoles and unsymmetrically 1,1'-disubstituted ferrocenes, bearing a
      triazole ring directly linked to the redox unit, behave as efficient ion-pair
      recognition receptors. 

PMID- 24136002
TI  - A systematic review of the effect of community treatment orders on service use.
AB  - PURPOSE: The evidence regarding community treatment order effectiveness has been
      conflicting. This systematic review aims to bring up to date the review performed
      by Churchill and colleagues in 2005 by assessing and interpreting evidence of CTO
      effectiveness defined by admission rates, number of inpatient days, community
      service use, and medication adherence published since 2006. METHOD: Databases
      were searched to obtain relevant studies published from January 2006 to March
      2013. RESULTS: 18 studies including one randomised controlled trial were
      included. There remains lack of evidence from randomised and non-randomised
      studies that CTOs are associated with or affected by admission rates, number of
      inpatient days or community service use. The most recent and largest RCT is
      included in this review and found no significant impact on admission rate (RR =
      1.0, 95% CI 0.75-1.33) or number of days in hospital (IR = 0.90, 95% CI 0.65
      1.26). Results from the two largest longitudinal datasets included in this review
      do not concur. Studies using the New York dataset found that CTOs were associated
      with reduced admission rates and inpatient days, while studies using the Victoria
      dataset generally found that they were associated with increased admission rates
      and inpatient days. CONCLUSION: There is now robust evidence in the literature
      that CTOs have no significant effects on hospitalisation and other service use
      outcomes. Non-randomised studies continue to report conflicting results.
      Distinguishing between CTO recall and revocation and different patterns of
      community contact is needed in future research to ensure differentiation between
      CTO process and outcome.

PMID- 24136005
TI  - Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop.
AB  - Self-reactive CD4 T cells are thought to have a central role in the pathogenesis
      of many chronic inflammatory human diseases. Microbial peptides can activate self
      reactive T cells, but the structural basis for such crossreactivity is not well
      understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with
      multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we
      report the structural mechanism of TCR crossreactivity with two distinct peptides
      from human pathogens. The structures show that a single TCR residue (CDR3alpha
      F95) makes the majority of contacts with the self-peptide and both microbial
      peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide
      MHC surface. Further, a neighbouring residue located on the same TCR loop
      (CDR3alpha E98) forms an energetically critical interaction with the MHC
      molecule. These data show how binding by a self-reactive TCR favors
      crossreactivity between self and microbial antigens. 

PMID- 24136006
TI  - Sequence and expression of an alpha-amylase gene in four related species of
      prickleback fishes (Teleostei: Stichaeidae): ontogenetic, dietary, and species
      level effects.
AB  - Partial alpha-amylase gene sequences were determined and alpha-amylase gene
      expression was quantified in four species of carnivorous, omnivorous, and
      herbivorous prickleback fishes (family Stichaeidae) to assess the effects of
      ontogeny, diet, and species on expression of this gene. Pairwise comparison of
      alpha-amylase nucleotide sequences revealed 96-98 % identity, and comparison of
      amino acid portions revealed 93-95 % similarity among the four prickleback
      species. Expression was determined using in situ hybridization and intensity of
      expression quantified using image analysis. Alpha-amylase expression level was
      compared in three feeding categories of the four species: (1) small, wild-caught
      carnivorous juveniles; (2) larger, wild-caught juveniles of the carnivorous
      species and the three that had shifted to herbivory or omnivory; and (3) larger,
      juveniles produced by feeding a low-starch artificial diet to small juveniles
      until they reached the size of the larger wild-caught juveniles. The results
      showed no dietary effect in any species but significant ontogenetic and species
      level effects in Cebidichthys violaceus, as well as in the sister species
      Xiphister mucosus and X. atropurpureus. Based on a phylogeny for the Stichaeidae
      produced for this study using two mtDNA genes and one nuclear gene, the
      ontogenetic dietary shifts to herbivory/omnivory evolved independently in C.
      violaceus and in the clade containing the two species of Xiphister. All three of
      these species increased alpha-amylase gene expression with increase in size and
      had higher expression than Anoplarchus purpurescens, which is a member of a
      third, stichaeid clade comprising carnivores. These results show the importance
      of alpha-amylase in the herbivores and omnivores.

PMID- 24136007
TI  - Weak hydrogen bonding interactions influence slip system activity and compaction
      behavior of pharmaceutical powders.
AB  - Markedly different mechanical behavior of powders of polymorphs, cocrystals,
      hydrate/anhydrate pairs, or structurally similar molecules has been attributed to
      the presence of active slip planes system in their crystal structures. Presence
      of slip planes in the crystal lattice allows easier slip under the applied
      compaction pressure. This allows greater plastic deformation of the powder and
      results into increased interparticulate bonding area and greater tensile strength
      of the compacts. Thus, based on this crystallographic feature, tableting
      performance of the active pharmaceutical ingredients can be predicted. Recently,
      we encountered a case where larger numbers of C?H...O type interactions across
      the proposed slip planes hinder the slip and thus resist plastic deformation of
      the powder under the applied compaction pressure. Hence, attention must be given
      to these types of interactions while identifying slip planes by visualization
      method. Generally, slip planes are visualized as flat layers often strengthened
      by a two-dimensional hydrogen-bonding network within the layers or planes. No
      hydrogen bonding should exist between these layers to consider them as slip
      planes. Moreover, one should also check the presence of C?H...O type interactions
      across these planes. Mercury software provides an option for visualization of
      these weak hydrogen bonding interactions. Hence, caution must be exercised while
      selecting appropriate solid form based on this crystallographic feature.

PMID- 24136008
TI  - Breast cancer multifocality and multicentricity and locoregional recurrence.
AB  - The impact of multifocal (MF) or multicentric (MC) breast cancer on locoregional
      (LR) control rates is unknown. Methods. MF was defined as two or more separate
      invasive tumors in the same quadrant of the breast. MC was defined as two or more
      separate invasive tumors occupying more than one quadrant of the same breast.
      Patients were categorized by LR treatment: breast conservation therapy (BCT; n =
      256), mastectomy (n = 466), or mastectomy plus postmastectomy radiation therapy
      (PMRT; n = 184). All patients with MC disease had mastectomy (10 patients treated
      with BCT for MC disease were excluded). The Kaplan-Meier product limit method was
      used to calculate 5-year LR control rate. Cox proportional hazards models were
      used to determine independent associations of multifocality or multicentricity
      with LR control. Results. A total of 906 patients had either MF disease (n = 673)
      or MC disease (n = 233). With median follow-up of 52 months, the 5-year LR
      control rate was 99% for MF, 96% for MC, and 98% for unifocal tumors (p = .44).
      Subset analysis revealed no difference in LR control regardless of the LR
      treatment (p = .67 for BCT, p = .37 for mastectomy, p = .29 for mastectomy plus
      PMRT). There were five in-breast recurrences after BCT in the MF group. MF and MC
      did not have an independent impact on LR control rate on multivariate analysis.
      Conclusion. MF and MC disease are not independent risk factors for LR recurrence.
      Patients with MF and MC breast cancer had rates of LR control similar to those of
      their unifocal counterparts. These data suggest that BCT is a safe option for
      patients with MF tumors and that MF or MC disease alone is not an indication for
      PMRT. 

PMID- 24136009
TI  - Pilot studies for personalized cancer medicine: focusing on the patient for
      treatment selection.
AB  - Advances in diagnostics and targeted therapies during the past decade have
      changed how oncology is viewed. "Stratified medicine" has emerged from the
      accumulated evidence garnered from matching targeted therapies with tumor
      molecular aberrations. Concomitantly, current knowledge derived from large-scale,
      massively parallel sequencing technologies and global research initiatives such
      as the international 1000 Genomes Project, the Cancer Genome Atlas, the
      International Cancer Genome Consortium, and publicly available catalogs such as
      the Catalogue of Somatic Mutations in Cancer and Genomics of Drug Sensitivity in
      Cancer have illuminated the utility of understanding the molecular basis of
      cancer through genome analysis. In addition, multiple collaborative efforts are
      widening the possibility of universally personalizing cancer care. Although
      several key challenges of personalized cancer medicine (PCM) need to be
      addressed, some pilot studies are transforming the way we analyze tumor tissue
      molecular aberrations, design clinical trials, and measure treatment efficacy.
      Taken together, these pilot studies are paving the way for clinical trials that
      are designed to empirically test the concept of PCM. In this paper, we describe
      lessons learned from the first pilot initiatives of PCM and how this knowledge is
      being used to design novel clinical trials. 

PMID- 24136010
TI  - Optimizing tyrosine kinase inhibitor therapy in gastrointestinal stromal tumors:
      exploring the benefits of continuous kinase suppression.
AB  - The oral tyrosine kinase inhibitor (TKI) imatinib has revolutionized the
      treatment of gastrointestinal stromal tumors (GISTs), most of which harbor
      oncogenic mutation in genes that encode the receptor tyrosine kinases KIT or
      PDGFA. Imatinib is the standard of care for patients with advanced GIST and for
      patients with primary GIST at significant risk of recurrence after surgery.
      Design. This review discusses data supporting continuous kinase suppression with
      imatinib and key issues, including response to imatinib reintroduction, effect of
      treatment interruption on secondary resistance to imatinib, and prognostic
      factors associated with sustained response to imatinib. Results. Long-term follow
      up results of the B2222 study and updated results of the BFR14 trial demonstrate
      that continuous imatinib treatment in patients with advanced GIST is associated
      with reduced risk of progression. For patients progressing on or intolerant of
      imatinib, continuing therapy with TKIs sunitinib followed by regorafenib is
      recommended. In the adjuvant setting, final results of the trial by the
      Scandinavian Sarcoma Group and the Sarcoma Group of the Arbeitsgemeinschaft
      Internistische Onkologie demonstrate that 3 years of adjuvant imatinib, compared
      with 1 year, significantly reduces the risk of recurrence and improves overall
      survival of patients with KIT-positive GIST at high risk of recurrence.
      Conclusions. Maintenance of therapy with TKIs is the key to successful treatment
      of GIST. Results from recent studies provide a strong rationale for continuous
      imatinib treatment for 3 years following surgical resection and long-term
      continuous administration in advanced or metastatic GIST. 

PMID- 24136011
TI  - Improvement of adequate use of warfarin for the elderly using decision tree-based
      approaches.
AB  - OBJECTIVES: Due to the narrow therapeutic range and high drug-to-drug
      interactions (DDIs), improving the adequate use of warfarin for the elderly is
      crucial in clinical practice. This study examines whether the effectiveness of
      using warfarin among elderly inpatients can be improved when machine learning
      techniques and data from the laboratory information system are incorporated.
      METHODS: Having employed 288 validated clinical cases in the DDI group and 89
      cases in the non-DDI group, we evaluate the prediction performance of seven
      classification techniques, with and without an Adaptive Boosting (AdaBoost)
      algorithm. Measures including accuracy, sensitivity, specificity and area under
      the curve are used to evaluate model performance. RESULTS: Decision tree-based
      classifiers outperform other investigated classifiers in all evaluation measures.
      The classifiers supplemented with AdaBoost can generally improve the performance.
      In addition, weight, congestive heart failure, and gender are among the top three
      critical variables affecting prediction accuracy for the non-DDI group, while
      age, ALT, and warfarin doses are the most influential factors for the DDI group.
      CONCLUSION: Medical decision support systems incorporating decision tree-based
      approaches improve predicting performance and thus may serve as a supplementary
      tool in clinical practice. Information from laboratory tests and inpatients'
      history should not be ignored because related variables are shown to be decisive
      in our prediction models, especially when the DDIs exist.

PMID- 24136012
TI  - Unraveling the origin of exponential law in intra-urban human mobility.
AB  - The vast majority of travel takes place within cities. Recently, new data has
      become available which allows for the discovery of urban mobility patterns which
      differ from established results about long distance travel. Specifically, the
      latest evidence increasingly points to exponential trip length distributions,
      contrary to the scaling laws observed on larger scales. In this paper, in order
      to explore the origin of the exponential law, we propose a new model which can
      predict individual flows in urban areas better. Based on the model, we explain
      the exponential law of intra-urban mobility as a result of the exponential
      decrease in average population density in urban areas. Indeed, both empirical and
      analytical results indicate that the trip length and the population density share
      the same exponential decaying rate. 

PMID- 24136014
TI  - Impulsive for life? The nature of long-term impulsivity in domestic dogs.
AB  - Individual differences in impulsivity occur at a cognitive and/or behavioural
      level and are associated with differing life outcomes. However, there is a lack
      of empirical evidence to support the long-term stability of these characteristics
      in non-human animals. This study reports on the stability of convergent measures
      of impulsivity in domestic dogs assessed more than 6 years apart. Measures were
      (1) owner assessment by means of a questionnaire, the validated 'Dog Impulsivity
      Assessment Scale' (DIAS) and (2) dogs' performance in a delayed reward choice
      test. Dogs had 15-min free access to two food dispensers, one dispensing a piece
      of food immediately, the other dispensing three pieces after a delay, which
      increased by 1 s every other time the dogs sampled it. Maximum delay reached in
      this task reflects decision-making, or cognitive impulsivity, whereas the rate of
      extra presses on the delayed reward device during the delay can be considered as
      a measure of motor or behavioural impulsivity. DIAS scores were strongly and
      significantly correlated across years. The maximum delay reached in the behaviour
      test was also highly stable, whereas paw-pressing rate was uncorrelated between
      the years. These results demonstrate that cognitive but not motor impulsivity is
      highly consistent over time in dogs.

PMID- 24136015
TI  - The efficacy of vitamin K2 and calcitriol combination on thalassemic osteopathy.
AB  - Thalassemic osteopathy (TOSP) has emerged as a topic of interest, as the
      optimized transfusion regimens and iron chelations has markedly improved the
      survival of the patients suffering from thalassemia major (TM) and increased the
      life expectancy. The aim of this prospective monocentric pilot study was to
      investigate the effects of a dietary supplement with vitamin K2 (50 mcg
      menaquinone-7) and vitamin D (5 mcg calcitriol) on the patients with TOSP. Twenty
      children (12 girls, 8 boys; age varied from 3 to 18 y) with beta TM, who
      underwent regular blood transfusion and iron chelation therapy, were enrolled in
      this study and investigated at the initial, sixth, and 12th month of the
      treatment. We detected a significant improvement in the bone mineral density and
      Z-score at the lumbar spine area of the patients at the sixth and 12th month of
      the treatment, especially in the prepubertal group. We also found a decrease in
      the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin, however,
      this was not found to be significant. Although the natural course of TOSP is
      worsening or at least stabilizing, our pilot study demonstrated that vitamin K2
      and calcitriol combination clearly has a positive effect on the bone mineral
      density of the children with TM during a 1-year period. Supplementation of
      menaquinone-7 instead of drugs is an augmented physiological intake and seems a
      beneficial alternative for the treatment of TOSP. Further studies on a large
      number of participants are necessary to highlight the effect of vitamin K2 on
      TOSP. 

PMID- 24136016
TI  - Appropriate modulation of autophagy sensitizes malignant peripheral nerve sheath
      tumor cells to treatment with imatinib mesylate.
AB  - Malignant peripheral nerve sheath tumor (MPNST), very rare in childhood, is a
      highly aggressive soft-tissue tumor. We experienced a case of a 7-year-old boy
      with MPNST who was treated with imatinib mesylate (imatinib) after the
      identification of platelet-derived growth factor receptor expression in his
      tumor. We were unable to observe clinical benefits of imatinib in this patient.
      Therefore, cellular reactions of imatinib were investigated in vitro using 3
      MPNST cell lines. Imatinib induced cytotoxicity in vitro with variable IC50
      values (11.7 to >30 MUM). Induction of apoptosis was not a pivotal mechanism in
      the inhibitory effects. We found that the treatment of MPNST cell lines with
      imatinib induced autophagy. Suppression of the initiation of autophagy by 3
      methyladenine or small interfering RNA (siRNA) against beclin-1 attenuated the
      imatinib-mediated cytotoxicity. In contrast, blocking the formation of
      autophagosomes or the development of autolysosomes using siRNA against
      microtubule-associated protein light chain 3B, bafilomycin A1, chloroquine, or an
      MEK1/2 inhibitor (U0126) enhanced the imatinib-induced cytotoxicity in MPNST
      cells. Our data showed that the imatinib-mediated autophagy can function as a
      cytotoxic mechanism and that appropriate modulation of autophagy may sensitize
      MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for
      MPNST. 

PMID- 24136017
TI  - Management of refractory pain in hospitalized adolescents with sickle cell
      disease: changing from intravenous opioids to continuous infusion epidural
      analgesia.
AB  - BACKGROUND: Prolonged hospitalizations for sickle cell disease painful episodes
      are not uncommon, as analgesic options are often suboptimal. OBSERVATIONS: Seven
      patients (15.4 +/- 3.7 y, 6 females) were treated with epidural analgesia for
      refractory pain. The median duration of epidural catheter placement was 4 days
      (interquartile range, 3 to 6 d). Mean pain scores changed from 6.8 +/- 2.7 to 4.8
      +/- 2.2, whereas mean daily parenteral opioid requirements changed from 79.7 +/-
      100.4 to 13.0 +/- 13.1 mg of morphine equivalents. CONCLUSION: Continuous
      epidural analgesia is an alternative to continuing intravenous opioids in sickle
      cell disease patients with refractory pain, and may reduce opioid-related side
      effects and facilitate transition to oral analgesics.

PMID- 24136018
TI  - Oncology house physician model: a response to changes in pediatric resident
      coverage.
AB  - BACKGROUND: Given decreasing resident duty hours, subspecialty hospitalist models
      have emerged to help compensate for the restructured presence of residents. We
      sought to examine the impact of our pediatric oncology hospitalist model on the
      oncology unit staff. PROCEDURE: The survey was developed after a literature
      review of subspecialty hospitalist models. The final surveys were designed using
      a 5-point Likert scale. Descriptive statistics were used to compile baseline
      demographic characteristics of respondents and overall responses to survey
      questions. RESULTS: Respondents agreed that house physicians provide better
      continuity of care (96.8%), are more comfortable with the experience level of the
      physician (98.4%), and are better able to answer questions (92%). Respondents
      also agreed that house physicians serve as backup for system-related and patient
      related questions and found security knowing an experienced provider was on the
      floor (87.5%). Responses to open-ended questions indicated that the house
      physician model has impacted fellow education. CONCLUSIONS: Our oncology house
      physician model helps account for decreased residency duty hours. This can serve
      as a model for other institutions requiring subspecialty inpatient coverage,
      given resident work hour restrictions. Adjustments in the clinical education of
      hematology/oncology fellows need to be considered in the setting of competent,
      consistent, and experienced front-line providers.

PMID- 24136019
TI  - Assessment of corticosteroid-induced osteonecrosis in children undergoing
      chemotherapy for acute lymphoblastic leukemia: a report from the Japanese
      Childhood Cancer and Leukemia Study Group.
AB  - Steroid-induced osteonecrosis (ON) is a challenging complication encountered
      during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We
      retrospectively assessed the incidence of ON and its risk factors in a total of
      1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia
      Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004],
      n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of
      whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941,
      0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in
      which only prednisolone was administered as a steroid, was significantly lower
      than that in ALL2004, in which dexamethasone was used as a partial substitute for
      prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with
      the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10
      y vs. 15.6% for age >=10 y, P<0.0001), suggesting that girls aged 10 years and
      above are at a greater risk of ON onset. These results indicate that the risk of
      ON should be considered when administering dexamethasone as part of ALL protocol
      treatment in girls aged 10 years and above. 

PMID- 24136020
TI  - Variable genotype-phenotype correlations in patients with a rare nondeletional
      alpha-thalassemia; Hb Pak Num Po (HBA1: c.396_397insT).
AB  - Transfusion-dependent Hb H disease is rarely reported. In the majority of
      patients, it is caused mainly by alpha(0)-thalassemia from deletions of 2 linked
      alpha-globin genes and nondeletional mutations. Previously, we had described 2
      unrelated Thai patients with this condition because of compound heterozygosity of
      SEA-type deletion (--SEA/) and a novel nucleotide mutation: a thymine insertion
      at codon 131 of the alpha1 gene, namely, Hb Pak Num Po (Hb PNP, alphaalpha(PNP)).
      We herein describe the identification of 4 additional patients with Hb PNP with a
      broader genotype/phenotype spectrum and provide an overview of clinical
      management approaches including stem-cell transplantation.

PMID- 24136021
TI  - Influenza A/H1N1 in pediatric oncology patients.
AB  - BACKGROUND: Our aim was to determine the clinical and epidemiological features of
      pandemic influenza A/H1N1 in immunocompromised children with solid tumors and
      hematological malignancies. PATIENTS AND METHODS: A prospective study was
      conducted during the H1N1 pandemic between August 2009 and February 2010 in a
      pediatric hematology-oncology unit. Demographic and clinical data were obtained
      from all children with suspected H1N1 infection (high fever with or without
      respiratory symptoms). Laboratory diagnosis of influenza A/H1N1 was performed by
      means of polymerase chain reaction analysis of nasopharyngeal wash specimens.
      RESULTS: We identified 57 episodes of suspected influenza A/H1N1 infection in 40
      children. In all episodes, children were treated with oseltamivir and antibiotics
      until influenza A/H1N1 results were received. Of all episodes, 13 (22.8%) tested
      positive for influenza A/H1N1. Two of the H1N1-positive children (15.4%) had been
      previously immunized against influenza A/H1N1. No differences between H1N1
      positive and H1N1-negative children were noted in terms of demographic features,
      clinical presentation, laboratory findings, and underlying disease.Three
      polymerase chain reaction-positive (23.0%) children and 1 H1N1-negative (2.3%)
      child were admitted to the pediatric intensive care unit and were mechanically
      ventilated (P=0.03). One (7.7%) H1N1-positive patient died versus none of the
      H1N1-negative patients (P=0.2). The condition of all other children in both the
      groups improved rapidly during hospitalization. CONCLUSIONS: Febrile hospitalized
      pediatric oncology patients, with and without pandemic influenza A/H1N1, had a
      similar demographic and clinical presentation with a relatively good outcome.
      This was probably because of early antiviral treatment and possibly because of
      the relatively low virulence of the virus. Immunization should be encouraged in
      these patients.

PMID- 24136022
TI  - Renal infarction secondary to invasive aspergillosis in a 5-year-old girl with
      acute lymphoblastic leukemia.
AB  - Aspergillus species have angioinvasive properties and can involve extrapulmonary
      organs by hematogenous spread from the lungs. However, renal involvement by
      Aspergillus is uncommon and is usually associated with the formation of
      abscesses. We report an unusual case of invasive renal aspergillosis presenting
      with extensive renal infarction in a 5-year-old girl with acute lymphoblastic
      leukemia. This case emphasizes the fact that renal aspergillosis initially
      presents with only renal infarction, and metastatic-embolism by invasive
      aspergillosis should be considered in differential diagnosis for any focal lesion
      of kidney in a patient with leukemia. 

PMID- 24136023
TI  - Radiation-induced gliomas in 2 pediatric patients with neurofibromatosis type 1:
      case study and summary of the literature.
AB  - Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes patients to
      the formation of sporadic tumors and also increases the risk of radiation-induced
      malignancies. The most commonly described radiation-induced tumor in NF1 patients
      is a malignant peripheral nerve sheath tumor. We present 2 children with NF1 who
      received radiation therapy and subsequently developed high-grade gliomas. We then
      review the current literature on radiation-induced tumors in NF1 patients.
      Although radiation may be the most appropriate therapy in specific situations for
      children with NF1, the secondary tumor risk should be carefully considered. 

PMID- 24136024
TI  - Dyskeratosis congenita complicated by hepatic fibrosis with hepatic vein
      thrombosis.
AB  - We describe the case of 2 male siblings with dyskeratosis congenita (DC).
      Extensive genetic analysis failed to identify a causative genetic abnormality.
      The elder brother developed hepatic fibrosis accompanied with hepatic vein
      thrombosis at the age of 9 years. Recent studies have found that patients with DC
      sometimes develop hepatic complications, including cirrhosis. However, little is
      known about hepatic complications in patients with DC who lack these mutations.
      Further genetic studies are required to understand the relationship between DC
      and hepatic complications. In addition, although danazol can sometimes be
      effective for treating bone marrow failure, hepatotoxicity can be a major
      complication. Therefore, when danazol is administered to patients with DC,
      careful monitoring for hepatic complications is important.

PMID- 24136025
TI  - A severe bleeding diathesis in a 6-year-old girl secondary to a composite
      diagnosis of splenic hemangiomatosis and small bowel lymphangiomatosis.
AB  - A 6-year-old girl presented with presumed relapse of childhood immune
      thrombocytopenia. Investigations revealed deranged coagulation parameters,
      abnormal small bowel thickening, and splenomegaly. A clinically significant
      bleeding diathesis emerged which was refractory to most hemostatic interventions.
      Laparatomy revealed a composite diagnosis of splenic hemangiomatosis and small
      bowel lymphangiomatosis. Splenectomy resulted in complete resolution of the
      coagulopathy. The diagnosis and management of these conditions is inherently
      complex and without clear guidance. We discuss our perioperative management of
      the bleeding diathesis. There is a need for long-term follow-up of the underlying
      pathologies particularly as potentially useful therapeutic agents have emerged. 

PMID- 24136026
TI  - Long-term survival (>13 years) in a child with recurrent diffuse pontine
      gliosarcoma: a case report.
AB  - Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The
      authors describe the case of an unusual pontine location of GS in a 9-year-old
      boy who was initially diagnosed with low-grade astrocytoma (LGA) that was
      successfully controlled for 4 years. Subsequently, his brain tumor transformed
      into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times,
      standard radiation therapy, and Gamma Knife procedure twice. His LGA was also
      treated with a standard chemotherapy regimen of carboplatin and vincristine, and
      his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with
      stem cell rescue and temozolomide. Unfortunately, he developed disseminated
      disease with multiple lesions and leptomeningeal involvement including a tumor
      occupying 80% of the pons. Upon presentation at our clinic, he had rapidly
      progressing disease. He received treatment with antineoplastons (ANP) A10 and AS2
      1 for 6 years and 10 months under special exception to our phase II protocol BT
      22. During his treatment with ANP his tumor stabilized, then decreased, and,
      ultimately, did not show any metabolic activity. The patient's response was
      evaluated by magnetic resonance imaging and positron emission tomography scans.
      His pathology diagnosis was confirmed by external neuropathologists, and his
      response to the treatment was determined by central radiology review. He
      experienced the following treatment-related, reversible toxicities with ANP:
      fatigue, xerostomia and urinary frequency (grade 1), diarrhea, incontinence and
      urine color change (grade 2), and grade 4 hypernatremia. His condition continued
      to improve after treatment with ANP and, currently, he complains only of residual
      neurological deficit from his previous surgery. He achieved a complete response,
      and his overall and progression-free survival is in excess of 13 years. This
      report indicates that it is possible to obtain long-term survival of a child with
      a highly aggressive recurrent GS with diffuse pontine involvement with a
      currently available investigational treatment. 

PMID- 24136027
TI  - Long-term follow-up of homozygote protein C deficiency after multimodal therapy.
AB  - Homozygous protein C deficiency is an extremely rare condition presenting in the
      neonatal period with purpura fulminans, with very high rates of morbidity and
      mortality. Optimal treatment for this condition is highly complex, poorly
      understood, and often limited by cost and product supply. We report a child who
      presented 2 days after birth with purpura fulminans and severe prenatal eye
      damage, but no cerebral lesions. He was treated with novel multimodal therapy
      culminating in liver transplant at 3 years of age. The patient is now 12 years of
      age, well, with blindness as his only long-term deficit. 

PMID- 24136028
TI  - Insurance status as a sociodemographic risk factor for functional outcomes and
      health-related quality of life among youth with sickle cell disease.
AB  - Youth with sickle cell disease (SCD) are at risk for functional limitations and
      poor health-related quality of life (QoL). This study examined sociodemographic
      factors that may interact with medical complications to reduce functional ability
      and QoL among youth with SCD. Fifty-three patient/caregiver pairs (children 8 to
      18 years; M=12.3 y) with SCD completed the Functional Disability Inventory and
      Pediatric Quality of Life Inventory questionnaires. Medical database reviews were
      conducted to collect health care utilization, disease complications, and
      sociodemographic information; insurance type (public vs. private insurance) and
      family zip code to access Census tract data reflecting neighborhood distress.
      Insurance type, but not neighborhood sociodemographic risk indicators, was
      significantly associated with disease-related complications and QoL. There were
      significant differences in both health care utilization and QoL by insurance
      type. Complications were higher in the group with public insurance. Insurance
      type seems to be more strongly related to disease outcomes and QoL than
      neighborhood sociodemographic distress. Closer attention to the contribution of
      insurance type to health outcomes may provide important insight to potential
      barriers for disease management. These issues are critically important for health
      care efficiency and equity for poor and underserved children with chronic health
      conditions. 

PMID- 24136029
TI  - Infusional chemotherapy and medication errors in a tertiary care pediatric cancer
      unit in a resource-limited setting.
AB  - BACKGROUND: Drug administration is a multiprofessional process. The high toxicity
      and low therapeutic index of chemotherapy drugs make medication errors a
      significant problem, resulting in excessive patient morbidity and cost.
      OBJECTIVE: An audit of the delivery of infusional chemotherapy among pediatric
      inpatients was planned, with the objective of improving practice and minimizing
      errors. METHOD: An observational study was conducted between January and August
      2012. Patients were followed up from their premedication until the completion of
      postchemotherapy hydration and/or rescue drugs. Errors were recorded and
      classified by error type, cause, severity, unit location, medication involved,
      and harm caused. RESULTS: A total of 205 observations were made and 23(13.6%)
      errors recorded, of which 6 were intercepted. No life-threatening adverse drug
      event was recorded. The most important risk factor predisposing to errors was
      admission to nonpediatric ward (P=0.004). Documentation errors and incorrect
      infusion time were the 2 most common errors, whereas the most frequent error node
      was administration error. Appropriate steps were taken to prevent their
      reoccurrence. CONCLUSIONS: This study helped provide important information about
      the rate and epidemiology of medication errors, emphasizing on the role of audit
      in enabling development of appropriate error-reducing strategies, particularly in
      the context of quality assurance in hospitals.

PMID- 24136030
TI  - Immune thrombocytopenic purpura in a case of propionic acidemia: case report.

PMID- 24136031
TI  - Capsule commentary on Fuster et al., no detectable association between frequency
      of marijuana use and health or healthcare utilization among patients who screen
      positive for drug use.

PMID- 24136032
TI  - A post-2011 time motion study.

PMID- 24136033
TI  - Capsule commentary on Patrick et al., trends in insulin initiation and treatment
      intensification among patients with type 2 diabetes.

PMID- 24136034
TI  - Intraocular pressure control with Ahmed glaucoma drainage device in patients with
      cicatricial ocular surface disease-associated or aniridia-related glaucoma.
AB  - To analyze the control of intraocular pressure (IOP) with an Ahmed glaucoma
      drainage device (AGDD) in two groups of glaucoma patients--one with cicatricial
      ocular surface disease (COSD) and one with aniridia. This is a retrospective
      comparative case series of nine patients (11 eyes) with COSD and six patients (8
      eyes) with aniridia who underwent AGDD surgery to control IOP. The main outcome
      measure in both groups was stability of IOP between 6 and 21 mmHg. Mean IOP
      decreased significantly in both groups after AGDD surgery (29.6 +/- 8.7 vs 14.7
      +/- 2.5, p = 0.008 in the COSD group; 26.3 +/- 8.2 vs 15.3 +/- 5.8, p = 0.008 in
      the aniridia group). Over a mean post-surgery follow-up of 37.1 months in the
      COSD group, we managed to control IOP in nine eyes; IOP control was successful in
      87 % of eyes at 12 months and 58 % of eyes at 26 months. Over a mean post-surgery
      follow-up of 37.4 months in the aniridia group, we managed to control the IOP in
      seven eyes; IOP control was successful in 87 % of eyes at 12 months. AGDD surgery
      had no significant deleterious effect on visual acuity in either group. A severe
      complication occurred in one eye (1/8) in the aniridia group (lost vision due to
      retinal detachment) and in one eye (1/11) in the COSD group (tube exposure). AGDD
      surgery is effective in controlling IOP and has a low complication rate in COSD
      and aniridia patients; however, some of the complications are severe and prompt
      management is needed to prevent deleterious results.

PMID- 24136035
TI  - A flexible porous Cu(II) bis-imidazolate framework with ultrahigh concentration
      of active sites for efficient and recyclable CO2 capture.
AB  - By virtue of planar Cu2(MU-OH)2(2+) cluster units, a flexible porous metal
      azolate framework not only adsorbs large amounts of CO2 (19.6 wt% or 266 g L(-1)
      at 298 K and 1 atm) with a high zero-coverage adsorption enthalpy (-47 kJ mol(
      1)), but also desorbs quickly at very low temperatures.

PMID- 24136036
TI  - Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention
      and as the initial medical treatment of non-ST segment elevation acute coronary
      syndromes.
AB  - BACKGROUND: During percutaneous coronary intervention (PCI), and in non-ST
      segment elevation acute coronary syndromes (NSTEACS), the risk of acute vessel
      occlusion by thrombosis is high. Glycoprotein IIb/IIIa blockers strongly inhibit
      platelet aggregation and may prevent mortality and myocardial infarction. This is
      an update of a Cochrane review first published in 2001, and previously updated in
      2007 and 2010. OBJECTIVES: To assess the efficacy and safety effects of
      glycoprotein IIb/IIIa blockers when administered during PCI, and as initial
      medical treatment in patients with NSTEACS. SEARCH METHODS: We updated the
      searches of the Cochrane Central Register of Controlled Trials (CENTRAL) on The
      Cochrane Library (Issue 12, 2012), MEDLINE (OVID, 1946 to January Week 1 2013)
      and EMBASE (OVID, 1947 to Week 1 2013) on 11 January 2013. SELECTION CRITERIA:
      Randomised controlled trials comparing intravenous IIb/IIIa blockers with placebo
      or usual care. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      studies for inclusion, assessed trial quality and extracted data. We collected
      major bleeding as adverse effect information from the trials. We used odds ratios
      (OR) and 95% confidence intervals (CI) for effect measures. MAIN RESULTS: Sixty
      trials involving 66,689 patients were included. During PCI (48 trials with 33,513
      participants) glycoprotein IIb/IIIa blockers decreased all-cause mortality at 30
      days (OR 0.79, 95% CI 0.64 to 0.97) but not at six months (OR 0.90, 95% CI 0.77
      to 1.05). All-cause death or myocardial infarction was decreased both at 30 days
      (OR 0.66, 95% CI 0.60 to 0.72) and at six months (OR 0.75, 95% CI 0.64 to 0.86),
      although severe bleeding was increased (OR 1.39, 95% CI 1.21 to 1.61; absolute
      risk increase (ARI) 8.0 per 1000). The efficacy results were homogeneous for
      every endpoint according to the clinical condition of the patients, but were less
      marked for patients pre-treated with clopidogrel, especially in patients without
      acute coronary syndromes.As initial medical treatment of NSTEACS (12 trials with
      33,176 participants), IIb/IIIa blockers did not decrease mortality at 30 days (OR
      0.90, 95% CI 0.79 to 1.02) or at six months (OR 1.00, 95% CI 0.87 to 1.15), but
      slightly decreased death or myocardial infarction at 30 days (OR 0.91, 95% CI
      0.85 to 0.98) and at six months (OR 0.88, 95% CI 0.81 to 0.96), although severe
      bleeding was increased (OR 1.29, 95% CI 1.14 to 1.45; ARI 1.4 per 1000). AUTHORS'
      CONCLUSIONS: When administered during PCI, intravenous glycoprotein IIb/IIIa
      blockers reduce the risk of all-cause death at 30 days but not at six months, and
      reduce the risk of death or myocardial infarction at 30 days and at six months,
      at a price of an increase in the risk of severe bleeding. The efficacy effects
      are homogeneous but are less marked in patients pre-treated with clopidogrel
      where they seem to be effective only in patients with acute coronary syndromes.
      When administered as initial medical treatment in patients with NSTEACS, these
      agents do not reduce mortality although they slightly reduce the risk of death or
      myocardial infarction.

PMID- 24136037
TI  - Corticosteroids for viral myocarditis.
AB  - BACKGROUND: Myocarditis is defined as inflammation of the myocardium accompanied
      by myocellular necrosis. Experimental evidence suggests that autoimmune
      mechanisms follow viral infection, resulting in inflammation and necrosis in the
      myocardium. However, the use of corticosteroids as immunosuppressives for this
      condition remains controversial. OBJECTIVES: The existing review was updated. The
      primary objective of this review is to assess the beneficial and harmful effects
      of treating acute or chronic viral myocarditis with corticosteroids. The
      secondary objective is to determine the best dose regimen. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of
      12, 2012) on The Cochrane Library, MEDLINE OVID (1946 to July Week 2, 2012),
      EMBASE OVID (1980 to Week 29, 2012), BIOSIS Previews (1969 to 20 July 2012), ISI
      Web of Science (1970 to 20th July, 2012), and LILACS (from its inception to 25
      July, 2012) , Chinese Biomed Database, CNKI and WANFANG Databases (from their
      inception to 31 December 2012). We applied no language restrictions. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for viral
      myocarditis compared with no intervention, placebo, supportive therapy, antiviral
      agents therapy or conventional therapy, including trials of corticosteroids plus
      other treatment versus other treatment alone, irrespective of blinding,
      publication status, or language. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data independently. Results were presented as risk ratios (RRs) and
      mean differences (MDs), both with 95% confidence intervals (CIs). MAIN RESULTS:
      Eight RCTs (with 719 participants) were included in this update. The trials were
      small in size and methodological quality was poor. Viral detection was performed
      in 38% of participants, among whom 56% had positive results. Mortality between
      corticosteroids and control groups was non-significant (RR, 0.93, 95% CI 0.70 to
      1.24). At 1 to 3 months follow-up, left ventricular ejection fraction (LVEF) was
      higher in the corticosteroids group compared to the control group (MD 7.36%, 95%
      CI 4.94 to 9.79), but there was substantial heterogeneity. Benefits were observed
      in LVEF in two trials with 200 children given corticosteroids (MD 9.00%, 95% CI
      7.48 to 10.52). New York Heart Association (NYHA) class and left ventricular end
      stage systole diameter (LVESD) were not affected. Creatine phosphokinase (CPK)
      (MD -104.00 U/L, 95% CI -115.18 to -92.82), Isoenzyme of creatine phosphate MB
      (CKMB) (MD 10.35 U/L, 95% CI 8.92 to 11.78), were reduced in the corticosteroids
      group compared to the control group, although the evidence is limited to small
      participant numbers. There were insufficient data on adverse events. AUTHORS'
      CONCLUSIONS: For people diagnosed with viral myocarditis and low LVEF,
      corticosteroids do not reduce mortality. They may improve cardiac function but
      the trials were of low quality and small size so this finding must be regarded as
      uncertain. High-quality, large-scale RCTs should be careful designed to determine
      the role of corticosteroid treatment for viral myocarditis. Adverse events should
      also be carefully evaluated.

PMID- 24136038
TI  - Rebuttal from Dr Jain et al.

PMID- 24136039
TI  - Draft genome of the kiwifruit Actinidia chinensis.
AB  - The kiwifruit (Actinidia chinensis) is an economically and nutritionally
      important fruit crop with remarkably high vitamin C content. Here we report the
      draft genome sequence of a heterozygous kiwifruit, assembled from ~140-fold next
      generation sequencing data. The assembled genome has a total length of 616.1 Mb
      and contains 39,040 genes. Comparative genomic analysis reveals that the
      kiwifruit has undergone an ancient hexaploidization event (gamma) shared by core
      eudicots and two more recent whole-genome duplication events. Both recent
      duplication events occurred after the divergence of kiwifruit from tomato and
      potato and have contributed to the neofunctionalization of genes involved in
      regulating important kiwifruit characteristics, such as fruit vitamin C,
      flavonoid and carotenoid metabolism. As the first sequenced species in the
      Ericales, the kiwifruit genome sequence provides a valuable resource not only for
      biological discovery and crop improvement but also for evolutionary and
      comparative genomics analysis, particularly in the asterid lineage.

PMID- 24136041
TI  - hMPV lineage nomenclature and heparin binding.
AB  - Human metapneumovirus (hMPV), first described in 2001 [1], is responsible for
      causing serious respiratory illness in young children, the elderly and
      immunocompromised patients. Four distinct lineages of hMPV have been identified
      with the original nomenclature for these subgroups (A1, A2, B1 and B2), reported
      by van den Hoogen et al. [2], utilised by many. An alternate terminology (1A, 1B,
      2A and 2B) was also published by Ishiguro et al. in 2004 [3] which has been
      adopted by others. However, this has caused some confusion in the interpretation
      of publication results as the terminology is similar yet describes different
      subtypes. As a result, a number of investigators have made a submission to the
      International Committee on Taxonomy of Viruses (ICTV, ICTV taxonomic proposal
      2012.012V) for the official adoption of the original terminology as an approved
      nomenclature for hMPV [4]. We welcome this officially approved nomenclature which
      should provide clarification of these subtypes in future. Therefore to assist
      with the interpretation of our recently published research in the 2012 special
      issue of Viruses: Pneumoviruses and Metapneumoviruses entitled "Diversity in
      Glycosaminoglycan Binding Amongst hMPV G Protein Lineages" [5] we have updated
      the Figure 3 in this letter (see Figure 1), showing the proposed ICTV terminology
      compared to the Ishiguro classification (used in our publication). Note that in
      the original publication the alphanumeric order for the Ishiguro classification
      was transposed (e.g., 1A was referred to as A1). 

PMID- 24136040
TI  - Oligopeptide m13 phage display in pathogen research.
AB  - Phage display has become an established, widely used method for selection of
      peptides, antibodies or alternative scaffolds. The use of phage display for the
      selection of antigens from genomic or cDNA libraries of pathogens which is an
      alternative to the classical way of identifying immunogenic proteins is not well
      known. In recent years several new applications for oligopeptide phage display in
      disease related fields have been developed which has led to the identification of
      various new antigens. These novel identified immunogenic proteins provide new
      insights into host pathogen interactions and can be used for the development of
      new diagnostic tests and vaccines. In this review we focus on the M13
      oligopeptide phage display system for pathogen research but will also give
      examples for lambda phage display and for applications in other disease related
      fields. In addition, a detailed technical work flow for the identification of
      immunogenic oligopeptides using the pHORF system is given. The described
      identification of immunogenic proteins of pathogens using oligopeptide phage
      display can be linked to antibody phage display resulting in a vaccine pipeline. 

PMID- 24136042
TI  - A sensitive monitoring system for mammalian cell cultivation processes: a PAT
      approach.
AB  - Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells,
      which must be monitored to comply with good manufacturing practice. We,
      therefore, developed a fully automated system comprising a specific exhaust gas
      analyzer, inline analytics and a corresponding algorithm to precisely determine
      the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer
      rate, transfer quotient and respiratory quotient without interrupting the ongoing
      cultivation, in order to assess its reproducibility. The system was verified
      using chemical simulation experiments and was able to measure the respiratory
      activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary
      cells) with satisfactory results at a minimum viable cell density of ~2.0 * 10(5)
      cells ml(-1). The system was suitable for both batch and fed-batch cultivations
      in bubble-aerated and membrane-aerated reactors, with and without the control of
      pH and dissolved oxygen. 

PMID- 24136044
TI  - Assessing pollution in Izmir Bay from rivers in western Turkey: heavy metals.
AB  - Urban rivers having different catchment areas and properties are investigated in
      order to infer their heavy metal contribution to the Izmir Inner Bay. The
      concentrations of Cd, Cr, Cu, Ni, Pb, and Zn in the waters and sediments of these
      rivers were measured and compared with the limit values given in the Sediment
      Quality Guidelines and Screening Quick Reference Tables (SQuiRTs). Metal
      concentrations in the sediments were determined to be between 0.5 and 3.5 mg kg(
      1), 10 to 221.5 mg kg(-1), 28 to 153.5 mg kg(-1), 13 to 103.5 mg kg(-1), 31.5 to
      157 mg kg(-1), and 124 to 1065.5 mg kg(-1) for Cd, Cr, Cu, Ni, Pb, and Zn,
      respectively. Higher metal concentrations in river waters were observed in rainy
      seasons, and Cu and Zn were frequently found above the critical limits. The
      correlations between the concentrations in waters, sediments, and wash off fluxes
      of the river catchments were statistically investigated and evaluated. Strong
      correlations between Ni-Cr (r = 0.618, p < 0.01), Ni-Zn (r = 0.578, p < 0.01),
      and Zn-Pb (r = 0.590, p < 0.01) concentrations in water were found. The metal
      load entering the inner bay was found to be 28.2 tons per year. The fluxes (mg m(
      2) per day) were generally high in large catchments with high annual flows, in
      regions with high runoff coefficients, and in areas hosting industrial
      activities. The strong correlations between the heavy metal fluxes suggest that
      the atmospheric pollution, which influences the whole city, may be the major
      source of these metals. 

PMID- 24136046
TI  - Response to a comment regarding "Reconstruction of posterior glenoid deficiency
      using distal tibial osteoarticular allograft".

PMID- 24136045
TI  - A standardised outcome measure of pain, symptoms and physical function in
      patients with hip and groin disability due to femoro-acetabular impingement:
      cross-cultural adaptation and validation of the international Hip Outcome Tool
      (iHOT12) in Swedish.
AB  - PURPOSE: There is a lack of standardised outcome measures in Swedish for active,
      young and middle-aged patients with hip and groin disability. The purpose of this
      study was to adapt the English version of the international Hip Outcome Tool
      (iHOT12) patient-reported outcome instrument for use in Swedish patients and
      evaluate the adaptation according to the consensus-based standards for the
      selection of health status measurement instruments checklist. METHODS: Cross
      cultural adaptation was performed in several steps, including translation, back
      translation, expert review and pre-testing. The final version was evaluated for
      reliability, validity and responsiveness in a clinical study of patients [median
      age 37 (range 15-75)], undergoing surgery for femoro-acetabular impingement.
      RESULTS: Cronbach's alpha was 0.89, and significant correlations were obtained
      with the Copenhagen Hip and Groin Outcome Score (Spearman's r 0.10-0.70; p <
      0.05) and the EuroQol, EQ-5D average score (Spearman's r 0.27-0.56; p < 0.01).
      Test-retest reliability (intraclass correlation coefficient) ranged from 0.59 to
      0.93 for the individual items. The smallest detectable change ranged from 17.1 to
      44.9 at individual level and 3.6 to 9.4 at group level. Factor analysis revealed
      one factor of pain and symptoms and another factor of physical function. Effect
      sizes were generally medium or large. CONCLUSION: The Swedish version of the
      iHOT12 is a valid, reliable and responsive instrument that can be used both for
      research and in the clinical setting.

PMID- 24136047
TI  - Effect of Preoperative Tracheal Stretch Exercise on Anterior Cervical Spine
      Surgery: A Retrospective Study.
AB  - STUDY DESIGN: We designed a retrospective study on preoperative tracheal stretch
      exercise (TSE) before anterior cervical spine surgery. The changes in vital signs
      before and during the surgery and the postoperative clinical outcome were
      recorded and compared with none treated patients. OBJECTIVE: The aim of this
      study was to evaluate whether the preoperative TSE is beneficial to the anterior
      cervical spine surgery and clinical outcome. SUMMARY OF BACKGROUND DATA: Anterior
      approach to the cervical spine surgery requires prolonged retraction of the
      trachea and esophagus. Although the surgery can be managed to complete, related
      potential complications may occur. METHODS: This is a retrospective study on 128
      patients scheduled for anterior cervical spine surgery. Patients in the stretched
      group received preoperative TSE for 3 consecutive days before surgery, whereas
      the control group did not. During the preoperative exercise and the surgery, the
      changes in the vital signs were recorded and compared with the control group. The
      visual analogue scale, neck disability index (NDI), and the Clinical Symptom
      Score of the Japanese Orthopaedic Association (JOA) were also compared at
      different follow-up intervals, including 1, 3, and 6 months postoperation.
      RESULTS: The changes in blood pressure, heart rate, and respiratory and
      swallowing rates during the first exercise are significantly greater than those
      during the last exercise (P<0.05). During the surgery, changes in the vital signs
      in the exercise patients are also significantly smaller than those in control
      patients (P<0.05), excluding the blood oxygen saturation. The significant
      differences were also observed with the postoperative NDI and JOA scores between
      the exercise and control group at 6 months (P<0.05). CONCLUSIONS: Proper and
      systematic preoperative TSE has great significance for the success of anterior
      cervical spine surgery.

PMID- 24136048
TI  - The M6-C Cervical Disk Prosthesis: First Clinical Experience in 33 Patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To determine the short-term
      clinical succesrate of the M6-C cervical disk prosthesis in primary and secondary
      surgery. SUMMARY OF BACKGROUND DATA: Cervical disk arthroplasty (CDA) provides an
      alternative to anterior cervical decompression and fusion for the treatment of
      spondylotic radiculopathy or myelopathy. The prevention of adjacent segment
      disease (ASD), a possible complication of anterior cervical decompression and
      fusion, is its most cited--although unproven--benefit. Unlike older arthroplasty
      devices that rely on a ball-and-socket-type design, the M6-C cervical disk
      prosthesis represents a new generation of unconstrained implants, developed to
      achieve better restoration of natural segmental biomechanics. This device should
      therefore optimize clinical performance of CDA and reduce ASD. MATERIALS AND
      METHODS: All patients had preoperative computed tomography or magnetic resonance
      imaging and postoperative x-rays. Clinical outcome was assessed using the Neck
      Disability Index, a Visual Analog Scale, and the SF-36 questionnaire. Patients
      were asked about overall satisfaction and whether they would have the surgery
      again. RESULTS: Thirty-three patients were evaluated 17.1 months after surgery,
      on average. Nine patients had a history of cervical interventions. Results for
      Neck Disability Index, Visual Analog Scale, and SF-36 were significantly better
      among patients who had undergone primary surgery. In this group, 87.5% of
      patients reported a good or excellent result and 91.7% would have the procedure
      again. In contrast, all 4 device-related complications occurred in the small
      group of patients who had secondary surgery. CONCLUSIONS: The M6-C prosthesis
      appears to be a valuable addition to the CDA armatorium. It generates very good
      results in patients undergoing primary surgery, although its use in secondary
      surgery should be avoided. Longer follow-up is needed to determine to what
      measure this device can prevent ASD.

PMID- 24136049
TI  - Health care burden of anterior cervical spine surgery: national trends in
      hospital charges and length of stay, 2000-2009.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: Our goals were: (1) to document
      national trends in total hospital charges and length of stay (LOS) associated
      with anterior cervical spine procedures from 2000 through 2009 and (2) to
      evaluate how those trends relate to demographic factors. SUMMARY OF BACKGROUND
      DATA: Since 2000, the number of anterior cervical spine procedures has increased
      dramatically in the United States. MATERIALS AND METHODS: We reviewed 86,622,872
      hospital discharge records (2000-2009) from the Nationwide Inpatient Sample and
      used ICD-9-CM codes to identify anterior cervical spine procedures (927,103). We
      assessed those records for outcomes (total hospital charges, LOS) and covariates
      (age, sex, race/ethnicity, insurance status, geographic location, comorbidities,
      presence of traumatic cervical spine injury on admission) of interest and
      determined (with multivariable linear regression models) the independent effects
      of covariates on outcomes (significance, P<0.05). RESULTS: From 2000 through
      2009, yearly charges significantly increased ($1.62 billion to $5.63 billion,
      respectively) and LOS significantly decreased (2.23+/-0.043 d to 2.20+/-0.045 d,
      respectively). The average hospital charges increased yearly after adjustment for
      covariates. All covariates but age were significant, independent predictors of
      hospital charges and LOS. CONCLUSIONS: To our knowledge, this investigation is
      the first to identify the significant demographic predictors of hospital charges
      and LOS associated with anterior cervical spine surgery.

PMID- 24136050
TI  - Management and Outcomes of Cerebrospinal Fluid Leak Associated With Anterior
      Decompression for Cervical Ossification of the Posterior Longitudinal Ligament
      With or Without Dural Ossification.
AB  - STUDY DESIGN: A retrospective clinical study. OBJECTIVE: To analyze and evaluate
      the clinical outcomes of cerebrospinal fluid (CSF) leak after anterior
      decompression for cervical ossification of the posterior longitudinal ligament
      (OPLL) with or without dural ossification (DO). SUMMARY OF BACKGROUND DATA:
      Anterior decompression can be highly efficacious in the treatment of OPLL.
      However, in some cases of OPLL, there often exists DO and fusion with the
      posterior longitudinal ligament, which may increase the chance for CSF leak
      during an anterior decompression surgery. MATERIALS AND METHODS: A retrospective
      analysis was performed on 126 OPLL patients (89 men and 37 women) treated with
      anterior decompression surgery between January 2008 and January 2012. The mean
      age at operation was 61 years (ranging from 46 to 72 y) and the average duration
      of diagnosis was 4.2 years (ranging from 3 d to 7 y). DO was present in 11
      patients, of whom 7 developed dural tear or defect. Among the 115 patients
      without DO, only 4 developed dural tear. Intraoperative dural repair was
      performed with gelatin foam onlay and fibrin glue seal. Postoperative care for
      CSF leak involved bed rest, CSF drainage, nutritional support, and antibiotics.
      RESULTS: A total of 11 cases associated with dural tear or defect developed
      postoperative CSF leak (an overall incidence of 8.7%). There was a statistically
      significant difference (P<0.001) in the incidence of CSF leak between the DO
      group (63.6%) and the non-DO group (3.5%). While leakage in 3 patients resolved
      spontaneously within 5 days of surgery, intermittent CSF cysts developed in 8
      patients. These were treated with circular pressure bandages, repeated
      aspiration, and lumbar drainage. All 8 cases resolved 14-30 days after surgery.
      These 11 patients were followed up for an average of 12.8 months (range of 1 to
      36 mo) with an average Japanese Orthopedic Association score of 51.2% and no
      significant neurological deficit or persistent headaches were recorded.
      CONCLUSIONS: Patients with DO are at increased risk for dural injury while
      undergoing anterior decompression for the treatment of OPLL. This is associated
      with a high incidence of CSF leak. However, the majority of patients with CSF
      leak could be managed conservatively.

PMID- 24136051
TI  - The Efficiency of Zero-profile Implant in Anterior Cervical Discectomy Fusion: A
      Prospective Controlled Long-term Follow-up Study.
AB  - STUDY DESIGN: A prospective controlled study. OBJECTIVE: The aim of this study
      was to compare the safety and efficacy of the zero-profile device with that of an
      anterior cervical plate and cage in patients undergoing anterior cervical
      discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: A series of studies
      have indicated that anterior instruments produce good clinical results during
      ACDF. However, common implants are associated with a high rate of postoperative
      complications. A cervical stand-alone cage with integrated fixation for zero
      profile segmental stabilization has been developed to solve this problem.
      MATERIALS AND METHODS: A total of 46 patients with cervical radiculopathy or
      myelopathy were randomly treated with an anterior plate and a cage or a new zero
      profile implant between September 2009 and April 2010. Patients were followed for
      2 years. The operation time, blood loss, exposure to radiation, the Japan
      Department of Orthopedics Association (JOA) score, pain Visual Analogue Score
      (VAS), and dysphagia score were recorded. RESULTS: The operation was completed
      successfully in 46 patients. Twenty-three patients received an anterior plate and
      cage (control group) and 23 patients received the new zero-profile implant (test
      group). Analysis of postoperative data at all protocol-defined intervals
      demonstrated improvement in all clinical outcomes for both the groups when
      compared with the corresponding preoperative data. No significant difference in
      VAS and JOA score was found in the 2 treatment groups. The test group had a
      greater reduction in dysphagia at all follow-up intervals, compared with the
      control group. No adjacent segment degeneration was found in the test group,
      whereas 4 patients in the control group developed degeneration in adjacent
      segments (P=0.045). Both the groups had no adverse events associated with the
      implant or implant surgery. CONCLUSIONS: The Zero-P implant is a viable
      alternative to ACDF in patients with persistently symptomatic, single-level
      cervical disk disease. The procedure requires more technical requirements than
      traditional plates.

PMID- 24136052
TI  - Surgical treatment of patients with spondylodiscitis and neurological deficits
      caused by spinal epidural abscess (SEA) is a predictor of clinical outcome.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study was to
      investigate the question whether surgical treatment of patients with
      spondylodiscitis and neurological deficits caused by a spinal epidural abscess
      (SEA) is a predictor of clinical outcome. SUMMARY OF BACKGROUND DATA:
      Spondylodiscitis with an accompanying SEA is a serious medical condition that is
      associated with potentially high risk for long-term neurological morbidity. In
      the literature, up to 75% of patients suffer from neurological deficits related
      to SEA in spondylodiscitis. Independent of treatment, residual neurology persists
      at a high rate. METHODS: A retrospective analysis of 135 patients admitted to our
      department due to a diagnosis of spondylodiscitis was performed. Presence of SEA
      was evaluated based on computed tomography and magnetic resonance imaging.
      Neurological status was documented on admission and at discharge according to the
      Frankel Score. In addition, our patient population was separated into group I
      without neurological deficits (Frankel E) and group II with abnormal Frankel A-D.
      Surgical and nonsurgical therapy was retrospectively evaluated. Data were
      statistically analyzed using the 2-sided Fisher exact test. RESULTS: On
      admission, 102 patients were graded as Frankel E in group I. In group II, 15 were
      Frankel D, 8 Frankel C, 8 Frankel B, and 2 Frankel A. After treatment, 105
      patients were Frankel E, 19 Frankel D, 4 Frankel C, 3 Frankel B, and none Frankel
      A. Four patients died because of severe comorbidities. In group II, 13 of 33
      patients had a SEA. Twelve patients showed improvement in Frankel grade, 1
      remained unchanged. Of the 20 patients in group II without a SEA, 11 improved and
      9 remained unchanged. Twenty-eight of the 33 patients in group II were treated
      surgically. Patients in both groups with improved neurology showed an upgrade by
      1 or 2 Frankel scores. There was no deterioration of neurology. The correlation
      between surgically treated patients with SEA in comparison with patients without
      SEA is considered to be statistically significant. CONCLUSION: Surgical treatment
      of patients with spondylodiscitis and neurological deficits caused by SEA is a
      predictor of clinical outcome.

PMID- 24136054
TI  - Sagittal Alignment of Spine and Spinal Cord for Upper Cervical Irreducible
      Atlantoaxial Kyphosis in Elderly Patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate clinical and
      radiographic outcome of posterior decompression and occipito-cervical/thoracic
      (OCT) fusion in patients with irreducible atlantoaxial kyphosis (IAK). SUMMARY OF
      BACKGROUND DATA: Posterior OCT fusion is an effective surgical procedure for
      treating IAK in the elderly. However, it is unclear whether correction can be
      obtained by the strong corrective force provided by implants, even in patients in
      whom reduction cannot be obtained preoperatively. There are no reports of
      improvement in patients in whom correction could not be achieved by a rigid
      system. METHODS: Twenty-five patients with IAK with mild vertical subluxation due
      to rheumatoid arthritis and 3 patients with IAK due to os odontoideum were
      treated with fossa magnum decompression, C1 laminectomy and OCT fusion. RESULTS:
      Mean follow-up period was 4.2 years. Preoperative and postoperative neurological
      findings revealed improvement by 1 or more grades in 18 of 28 (64.2%) patients.
      The parameters of spinal alignment, sagittal spinal cord alignment, and basilar
      invagination were evaluated on radiographs. No significant difference between
      preoperative and postoperative status was seen for the clivo-axial angle,
      occipito-upper cervical angle, atlantodental interval, or occipito-cervical 2
      angle, whereas significant improvement was seen in the cervico-medullary and
      dorsal CM angles (both P<0.05). No significant postoperative change in the
      vertical direction was seen for any of the parameters. Width of the spinal cord
      at the C1 level was significantly increased postoperatively, with a significant
      expansion of the cerebral spinal fluid space at the same level (P<0.05).
      CONCLUSIONS: Posterior decompression with fusion for the treatment of IAK in the
      elderly did not produce significant change in spinal alignment, but did
      significantly improve spinal cord alignment and local spinal cord compression at
      the C1 level, achieving satisfactory clinical outcomes.

PMID- 24136056
TI  - Two-Level Circumferential Lumbar Fusion Comparing Midline and Paraspinal
      Posterior Approach: 5-Year Interim Outcomes of a Randomized, Blinded, Prospective
      Study.
AB  - STUDY DESIGN: A prospective randomized and blinded comparative study of 2 patient
      groups with >5-year follow-up. OBJECTIVE: To compare the clinical outcomes and
      postoperative posterior muscle changes in patients with advanced degenerative
      disk disease undergoing 2-level circumferential spinal fusion using a posterior
      midline versus a paraspinal approach. SUMMARY OF BACKGROUND DATA: Lumbar spinal
      fusion is often performed using a circumferential (anterior and posterior)
      technique. Paraspinal muscle alterations occur during the retraction of the
      muscles required for posterior instrumentation and fusion bed preparation, which
      may adversely affect outcomes. METHODS: Patients with advanced 2-level lumbar
      degenerative disk disease were randomized into 2 groups of 25 each for the
      approach to the posterior spine for their anterior-posterior fusion. A midline
      posterior skin incision was universal, but all patients were blinded to the
      fascial incision and exposure to the posterior spine. All had intertransverse and
      facet joint fusions with pedicle screw instrumentation. Outcomes (visual analog
      back and leg pain scale, pain drawing, Oswestry disability index, and self
      assessment of procedure success) were assessed at various periods
      postoperatively. Preoperative and >1-year postoperative magnetic resonance images
      (MRI), including paraspinal muscles, were read by a radiologist who was blinded
      to the surgical approach and outcomes. RESULTS: No difference in operative time,
      blood loss, implant costs, or any other intraoperative parameter existed between
      the 2 patient groups. Although clinical improvement for all outcome scales was
      significant for both groups postoperatively, there was no difference between
      groups. Postoperative MRI T2 relaxation values were significantly increased at
      the operative levels and distally, but the changes were similar for both groups.
      CONCLUSIONS: Midline and paraspinal approaches result in similar outcomes in 2
      level spinal fusions. We were unable to demonstrate that a paraspinal muscle
      splitting approach to 2-level fusion was superior to the muscle-stripping midline
      approach. However, the study has low statistical power.

PMID- 24136060
TI  - Transforaminal Lumbar Interbody Fusion in Degenerative Disk Disease and
      Spondylolisthesis Grade I: Minimally Invasive Versus Open Surgery.
AB  - BACKGROUND: Interbody fusion represents an efficient surgical treatment in
      degenerative lumbar disease, achieving satisfying outcome in >90% of cases.
      Various studies have affirmed the advantages of percutaneous and minimally
      invasive techniques with regard to minimized damage on soft tissues during
      surgical procedure, but their efficacy in comparison with the classic open
      surgical procedures has not yet been demonstrated. MATERIALS AND METHODS: This is
      a retrospective study. We compared 30 consecutive patients affected by disk
      degenerative disease or grade I degenerative spondylolisthesis that were treated
      with minimally invasive transforaminal lumbar interbody fusion (mini-TLIF) to a
      group of 34 consecutive patients presenting similar pathologic findings and
      demographic characteristics that underwent interbody fusion by traditional open
      approach (open-TLIF). All patients were treated between 2006 and 2010. Patients'
      mean age was 46 years (min 28-max 56) and 51 years (min 32-max 58), respectively.
      Mean follow-up was 23 months (min 12-max 38) and 25 months (min 12-max 40),
      respectively. Clinical evaluation was performed by using Visual Analogue Scale
      (VAS) and Oswestry Disability Index (ODI) questionnaires. Radiographic evaluation
      was performed on standing and dynamic x-rays before operation and at final follow
      up. RESULTS: There was a statistically significant improvement in clinical scores
      (VAS and ODI) in both groups. Early postoperative VAS score was significantly
      lower in the mini-TLIF group. Mean hospital stay and mean blood loss were
      significantly higher in the open-TLIF group than in the mini-TLIF group (7.4 vs.
      4.1 d and 620 vs. 230 mL, respectively). Surgical time length of the procedure
      was higher in the mini-TLIF group. There were no major neurological complications
      in any of the patients. At final follow-up, radiographic evaluation showed good
      implant stability in both groups. CONCLUSIONS: Mini-TLIF is a safe and efficient
      procedure and, when correctly and carefully performed, can reach good results,
      similar to those obtained with traditional open surgical techniques, even though
      it may require a longer surgical time at least during the first stages of the
      learning curve. Reduced surgical invasiveness, short hospital stay, and limited
      blood loss represent the major advantages of minimally invasive technique.

PMID- 24136061
TI  - Clinical presentation of Puumala virus infections in southern Austria in the peak
      year 2012.
AB  - In 2012, an extraordinary rise in Puumala infections causing nephropathia
      epidemica (NE) was observed in southern Austria. We investigated differences in
      epidemiology, clinical presentation, laboratory results, treatment parameters,
      and outcome between patients in 2012 and previous years (2007-2011). All patients
      diagnosed with Puumala virus infections between 2007 and 2012 using a point of
      care Puumala IgM test at the microbiology laboratory, Department of Internal
      Medicine, Medical University of Graz, were included. In 2012, 42 and in 2007-2011
      a total of 40 patients were diagnosed with NE. In 2007-2011, patients presented
      more frequently with arthromyalgias (25% vs 7%, p = 0.027), while lower back pain
      was reported more often in 2012 (21% vs 5%, p = 0.029). Other symptoms occurred
      at the same rate. In 2012, patients were diagnosed significantly faster (time
      from first contact with a physician to diagnosis 1.3 +/- 0.2 vs 2.7 +/- 0.4 days,
      p = 0.01). Significantly fewer patients required haemodialysis in 2012 (2.4% vs
      20%, p = 0.01). There were no significant differences in laboratory parameters
      between the two groups. In the peak year 2012, patients were diagnosed faster and
      fewer patients required haemodialysis possibly because of the earlier diagnosis
      and earlier onset of therapy.

PMID- 24136062
TI  - Bacteria killing nanotechnology Bio-Kil effectively reduces bacterial burden in
      intensive care units.
AB  - A contaminated hospital environment has been identified as an important reservoir
      of pathogens causing healthcare-associated infections. This study is to evaluate
      the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial
      counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in
      the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles
      (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in
      the two single-bed rooms were provided by the sponsors. In the room S-20, the 10
      sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air
      conditioning filters were treated with Bio-Kil; and the surfaces of instruments
      (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon
      pads. Room S-19 served as the control. We compared the bacterial count on
      textiles and environment surfaces as well as air samples between the two rooms. A
      total of 1,364 samples from 22 different sites in each room were collected. The
      mean bacterial count on textiles and environmental surfaces in room S-20 was
      significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units
      [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples
      than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of
      microbial isolations was significantly greater among patients admitted to room S
      19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P <
      0.05). Bio-Kil can significantly reduce bacterial burden in the environment of
      the ICU.

PMID- 24136063
TI  - The prevalence of inflammatory back pain in a UK primary care population.
AB  - OBJECTIVE: Inflammatory back pain (IBP) is the earliest and most common symptom
      of axial SpA. However, there is very little information about the prevalence of
      IBP in the UK. In this cross-sectional cohort study we examined the prevalence of
      IBP in a UK primary care population using three published IBP criteria. METHODS:
      Potential participants aged 18-80 years were identified from the records of a
      large general practice in Norfolk, UK, with 17 177 patients. Read codes were used
      to identify those who had consulted their general practitioner on at least one
      occasion with back pain. A self-completed screening questionnaire was sent to a
      sample of 978 patients, enquiring about symptoms of IBP and extra-spinal
      manifestations of SpA. Questionnaire responses were used to determine whether
      patients met the Assessment of SpondyloArthritis international Society (ASAS),
      Calin and Berlin IBP criteria. RESULTS: Five hundred and five completed
      questionnaires were returned (response rate 51.6%). The median age of respondents
      was 60 years [interquartile range (IQR) 48-67] and 44.8% were male. The minimum
      prevalence of IBP among patients with at least one previous consultation for back
      pain was 7.7% (95% CI 6.2, 9.5) using the ASAS criteria, 13.5% (11.5, 15.8) using
      the Calin criteria and 15.4% (13.3, 17.8) using the Berlin criteria. There was no
      significant difference in prevalence between men and women, and between different
      age groups. Extrapolated to the practice population as a whole, the minimum
      prevalence of IBP in a UK primary care population is 1.7-3.4%. CONCLUSION: The
      prevalence of IBP varies significantly depending on the criteria used for
      classification.

PMID- 24136064
TI  - Costs of rheumatoid arthritis during the period 1990-2010: a register-based cost
      of-illness study in Sweden.
AB  - OBJECTIVES: The objectives of this study were to analyse the total socio-economic
      impact of RA in Sweden during the period 1990-2010 and to analyse possible
      changes in costs during this period. The period was deliberately chosen to cover
      10 years before and 10 years after the introduction of biologic drugs. METHODS: A
      prevalence-based cost-of-illness study was conducted based on data from national
      and regional registries. RESULTS: There was a decrease in the utilization of RA
      related inpatient care as well as sick leave and disability pension during 1990
      2010 in Sweden. Total costs for RA are presented in current prices as well as
      inflation-adjusted with the consumer price index (CPI) and a healthcare price
      index. The total fixed cost of RA was ?454 million in 1990, adjusted to the price
      level of 2010 with the CPI. This cost increased to ?600 million in 2010 and the
      increase was mainly due to the substantially increasing costs for
      pharmaceuticals. Of the total costs, drug costs increased from 3% to 33% between
      1990 and 2010. Consequently the portion of total costs accounting for indirect
      costs for RA is lowered from 75% in 1990 to 58% in 2010. CONCLUSION: By inflation
      adjusting with the CPI, which is reasonable from a societal perspective, there
      was a 32% increase in the total fixed cost of RA between 1990 and 2010. This
      suggests that decreased hospitalization and indirect costs have not fallen enough
      to offset the increasing cost of drug treatment.

PMID- 24136065
TI  - Dual-energy computed tomography compared with ultrasound in the diagnosis of
      gout.
AB  - OBJECTIVES: The aim of our study was to compare dual-energy CT (DECT) with US for
      the diagnosis of gouty arthritis and to correlate the imaging findings with
      results from synovial fluid aspiration whenever possible. METHODS: We recruited
      21 patients (17 male and 4 female) who presented with a clinical suspicion of
      acute or chronic gout in 37 joints. DECT scans of the hands, wrists, feet,
      ankles, knees and elbows were performed. For post-processing, a colour-coding
      gout software protocol was used. US examinations of the same joints were
      performed. In addition, joint fluid aspiration was performed in a total of 14
      joints. RESULTS: DECT images were positive for urate crystal deposits in 25 of 37
      joints. US findings were positive in 24 of 37 examined joints. In 12 of 14 joints
      the synovial fluid aspiration was positive. CT and US findings correlated in 32
      of 37 joints (86.5%; kappa = 0.698, P < 0.001). CT and synovial fluid results
      correlated in 12 of 14 joints (85.7%; kappa = 0.417, P = 0.119). US and cytology
      findings correlated in 14 of 14 joints (100%; kappa = 1, P < 0.001). CONCLUSION:
      DECT and US have comparable sensitivity for the detection of gouty arthritis in a
      clinical setting. However, DECT results should be interpreted carefully, as there
      could be some false-negative findings.

PMID- 24136066
TI  - Synovial joint fluid cytokine levels in hip disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate cytokine level
      characteristics in the hip joint fluid, including rapidly destructive coxopathy
      (RDC), OA, osteonecrosis (ON) of the femoral head and RA. METHODS: Thirty-three
      hips with RDC, 57 with OA, 36 with ON and 10 with RA were included in the study.
      OA hips were divided into two groups: 20 hips with early OA without joint space
      narrowing and 37 hips with terminal OA. ON hips were divided into three groups:
      13 hips with <3 mm collapse, 14 hips with >3 mm collapse and 9 hips with terminal
      ON. Joint fluid was collected during surgery. Cytokine levels including IL-1beta,
      IL-6, IL-8 and TNF-alpha were measured using homogeneous time-resolved
      fluorescence. RESULTS: All measured cytokine levels in RDC were significantly
      higher than those in OA (P < 0.05). Terminal OA showed higher cytokine levels
      than those in early OA (P < 0.05). IL-6 and TNF-alpha levels in the ON group with
      >3 mm collapse were higher than those found in the ON group with <3 mm collapse.
      In comparing cytokine levels between RDC, terminal OA, RA and terminal ON, RDC
      showed significantly higher IL-8 levels than terminal OA and RA (P < 0.05).
      CONCLUSION: IL-8 levels in RDC were higher than in the other hip diseases. The IL
      8 level may reflect the aggressiveness of joint destruction in RDC, and IL-6 and
      TNF-alpha levels may also reflect ongoing destruction in OA and ON.

PMID- 24136067
TI  - Anti-TNF-alpha therapy prevents the recurrence of joint bleeding in haemophilia
      and arthritis.

PMID- 24136068
TI  - Frequency and predictors of premature work loss in primary care consulters for
      osteoarthritis: prospective cohort study.
AB  - OBJECTIVE: The objective of this study was to describe the extent of premature
      work loss (PWL) in OA consulters across a 6-year observation period, and
      associated factors. METHODS: We conducted a population-based prospective cohort
      study set in primary care. Participants were 1098 adults age 50 years to
      statutory retirement age at baseline, who completed questionnaires at baseline, 3
      and 6-year follow-ups. OA was defined by consultation to primary care (Read code
      N05) during the study period. PWL was defined as retirement prior to state
      retirement age (65 years for men, 60 years for women), off work due to health or
      unemployment. The frequency of PWL was calculated overall and stratified by
      consultation for OA. Bivariate and multivariate logistic regression was used to
      investigate the predictors of PWL in consulters for OA. RESULTS: Over the 6-year
      study period, one in four consulters for OA left the workplace prematurely.
      Predictors included being male, pain interference with function and lower co
      worker support, but not the extent of arthritis, co-morbidity, obesity or
      psychological or other job factors. CONCLUSION: PWL in persons consulting primary
      care general practitioners with OA is common. Those at risk could be identified
      by brief questions about pain interference with function and workplace support.
      These results suggest that early identification, treatment strategies focusing on
      maintaining function and maximizing workplace support should be investigated for
      their potential to prevent PWL. Good communication with employers may help to
      improve support for workers with OA.

PMID- 24136069
TI  - Onset age affects mortality and renal outcome of female systemic lupus
      erythematosus patients: a nationwide population-based study in Taiwan.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of disease
      onset age on mortality and renal survival in female SLE patients. METHODS: This
      nationwide, population-based, retrospective cohort study used data from the
      National Health Insurance Research Database of Taiwan. Female patients newly
      diagnosed with SLE from 2001 to 2004 were identified as the study cohort. A non
      SLE group was matched for age, sex and initial diagnosis date (index date) as the
      comparison cohort. Co-morbidities, mortality rates and end-stage renal disease
      (ESRD) incidences were compared among SLE patients of different onset age. Hazard
      ratios with a 95% CI were determined by the Cox proportional hazard model to
      quantify the mortality rates and ESRD incidences. Juvenile-onset, adult-onset and
      late-onset SLE patients were categorized according to disease onset age: <18, 18
      50 and >50 years old. RESULTS: In total, 513 juvenile-onset, 3076 adult-onset and
      764 late-onset SLE patients were identified. Compared with non-SLE controls, the
      hazard ratios of mortality were 6.49 (95% CI 3.73, 11.32, P < 0.001) for juvenile
      onset, 1.75 (95% CI 1.47, 2.08, P < 0.001) for adult-onset and 3.44 (95% CI 2.76,
      4.28, P < 0.001) for late-onset SLE patients. The hazard ratios of incident ESRD
      were 20.28 (95% CI 12.79, 32.15, P < 0.001) for adult-onset lupus patients and
      1.99 (95% CI 1.36, 2.93, P < 0.001) for late-onset patients. CONCLUSION: Female
      patients with late-onset SLE carried a higher risk of mortality than those with
      adult-onset disease in the presence of co-morbidities. Juvenile-onset SLE
      patients were at greatest risk of mortality, which is probably due to disease
      severity.

PMID- 24136070
TI  - Investigating monoclonal antibody aggregation using a combination of H/DX-MS and
      other biophysical measurements.
AB  - To determine how structural changes in antibodies are connected with aggregation,
      the structural areas of an antibody prone to and/or impacted by aggregation must
      be identified. In this work, the higher-order structure and biophysical
      properties of two different monoclonal antibody (mAb) monomers were compared with
      their simplest aggregated form, that is, dimers that naturally occurred during
      normal production and storage conditions. A combination of hydrogen/deuterium
      exchange mass spectrometry and other biophysical measurements was used to make
      the comparison. The results show that the dimerization process for one of the mAb
      monomers (mAb1) displayed no differences in its deuterium uptake between monomer
      and dimer forms. However, the other mAb monomer (mAb2) showed subtle changes in
      hydrogen/deuterium exchange as compared with its dimer form. In this case,
      differences observed were located in specific functional regions of the CH 2
      domain and the hinge region between CH 1 and CH 2 domains. The importance and the
      implications of these changes on the antibody structure and mechanism of
      aggregation are discussed.

PMID- 24136071
TI  - Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients.
AB  - Obesity increases the risk for venous thromboembolism (VTE), but whether high
      dose thromboprophylaxis is safe and effective in morbidly obese inpatients is
      unknown. It was the objective of this study to quantify the efficacy and safety
      of high-dose thromboprophylaxis with heparin or enoxaparin in inpatients with
      weight > 100 kilograms (kg) within the BJC HealthCare system. Ina retrospective
      cohort study, we analysed 9,241 inpatients with weight > 100 kg discharged from
      three hospitals in the BJC HealthCare system from 2010 through 2012. We compared
      the incidence of VTE in patients who received high-dose thromboprophylaxis
      (heparin 7,500 units three times daily or enoxaparin 40 mg twice daily) to those
      who received standard doses (heparin 5,000 units two or three times daily or
      enoxaparin 40 mg once daily). The primary efficacy outcome was hospital-acquired
      VTE identified by International Classification of Diseases (ICD)-9 diagnosis
      codes. The primary safety outcome was bleeding events identified by ICD-9 codes.
      Among the 3,928 morbidly obese inpatients (weight > 100 kg and body mass index
      [BMI] >= 40 kg/m2), high-dose thromboprophylaxis approximately halved the odds of
      symptomatic VTE (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.27-1.00; p
      = 0.050). The rate of VTE was 1.48% (35/2,369) in these morbidly obese inpatients
      who received standard doses of thromboprophylaxis, compared to 0.77% (12/1,559)
      in those who received high doses. High-dose thromboprophylaxis did not increase
      bleeding (OR 0.84, 95% CI 0.66-1.07, p = 0.15). Independent predictors of VTE
      were surgery, male sex, cancer, and BMI. In conclusion, high-dose
      thromboprophylaxis nearly halves the rate of VTE in morbidly obese inpatients. 

PMID- 24136072
TI  - Combination of a new oral anticoagulant, aspirin and clopidogrel after acute
      coronary syndrome: new therapeutic standard?
AB  - Effective secondary prevention after acute coronary syndrome (ACS) is largely
      dependent on dual antiplatelet therapy (DAPT). Despite DAPT, however, patients
      remain at substantial risk of major adverse cardiovascular events (i.e.,
      cardiovascular death, myocardial infarction, stroke), and, therefore, combination
      therapy of oral anticoagulant and antiplatelets has been previously proposed.
      Because of the increase in bleeding and the cumbersome management of vitamin K
      antagonists, such combination therapy has never gained much popularity. The
      recent development of new, non vitamin K antagonists, direct oral anticoagulants
      (NOACs), including dabigatran, apixaban, rivaroxaban, and darexaban, which have
      more favorable pharmacokinetics and pharmacodynamics, as well as higher safety,
      has renewed the interest on combination therapy. Whereas phase II trials with
      dabigatran, apixaban, rivaroxaban, and darexaban have consistently shown an
      increased bleeding risk with combination therapy, a potential increased efficacy
      has emerged for apixaban and rivaroxaban, thereby prompting phase III studies.
      Both APPRAISE-2 and ATLAS ACS 2-TIMI 51 trials confirm a dose-dependent increase
      in major bleeding events, including intracranial, with apixaban and rivaroxaban
      when combined with DAPT. Low-dose (2.5 mg twice daily) rivaroxaban on the other
      hand, is associated with a significantly higher efficacy on the occurrence of
      combined cardiovascular death, myocardial infarction, stroke, and of stent
      thrombosis. Owing to the persistent uncertainty regarding the net clinical
      benefit of combined therapy of NOAC, namely low-dose (2.5 mg twice daily)
      rivaroxaban and DAPT of aspirin and clopidogrel, further studies are warranted to
      identify the ACS patient who will benefit most from such treatment, also in
      comparison to the current therapeutic standard represented by DAPT of aspirin and
      ticagrelor (or prasugrel).

PMID- 24136073
TI  - Albright's hereditary osteodystrophy.

PMID- 24136074
TI  - Mastocytosis presenting as cardiac emergency.
AB  - Mastocytosis is characterised by clonal proliferation of mast cells in the skin
      and in various internal organs, and by symptoms related to an acute release of
      mast cell-derived mediators. In 20-30 % of patients, mastocytosis occurs without
      the typical skin lesions of urticaria pigmentosa that are usually the first
      clinical sign of the disease. In these patients, anaphylaxis is often the
      presenting sign of the disease. We report three cases in which a cardiac
      emergency (cardiac arrest or ventricular fibrillation) was the first clinical
      manifestation of anaphylaxis associated with systemic mastocytosis. All patients
      were men, none of them had previous episodes of anaphylaxis or other mediator
      related symptoms, and none had major pre-existing cardiovascular condition. An
      eliciting factor was identified in one case (a wasp sting), but one was found in
      the other two. Elevation of the serum tryptase suggested a mastocytosis, which
      was confirmed by bone marrow biopsy. This case series demonstrates that
      cardiovascular emergencies may be presenting signs of mastocytosis, and that
      elevation of serum tryptase after an acute cardiac event, if confirmed under
      basal conditions, may be useful for diagnosing this disease. 

PMID- 24136075
TI  - Naughty chaperone as a target for viral cancer.

PMID- 24136076
TI  - "A fortuitous combination of circumstances".

PMID- 24136077
TI  - IRF4(-/-)Vh11 mice: a novel mouse model of CLL.

PMID- 24136078
TI  - Targeting IDH: the next big thing in AML.

PMID- 24136079
TI  - 2B or not 2B: when VWF is not a good platelet friend.

PMID- 24136080
TI  - Assembling the machinery of coagulation.

PMID- 24136082
TI  - Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new
      injectable self-setting bone analogue.
AB  - An alternative approach to bone repair for less invasive surgical techniques,
      involves the development of biomaterials directly injectable into the injury
      sites and able to replicate a spatially organized platform with features of bone
      tissue. Here, the preparation and characterization of an innovative injectable
      bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is
      presented. The biopolymer features and the cement self-setting reaction were
      investigated by rheological analysis. The porous architecture, the evolution of
      surface morphology and the grains dimension were analyzed with electron
      microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by
      X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out
      to prove the positive effect of gelatin on the flow ensuing that cement is fully
      injectable. The cement mechanical properties are adequate to function as
      temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and
      bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and
      proliferate inside the pores, and hMSCs differentiated to the osteoblastic
      phenotype. The results are paving the way for an injectable bone substitute with
      properties that mimic natural bone tissue allowing the successful use as bone
      filler for craniofacial and orthopedic reconstructions in regenerative medicine. 

PMID- 24136083
TI  - The foramen magnum in isolated and syndromic brachycephaly.
AB  - BACKGROUND: Though the foramen magnum (FM) is often altered in complex
      craniosynostosis, no study analysed the FM dimensions in patients with
      brachycephaly specifically. PATIENTS AND METHODS: We measured the FM area,
      sagittal and transverse diameters on preoperative CT scans in patients with
      bicoronal synostosis (n = 40) and age-matched control group (n = 18). Our study
      included 16 children with FGFR3 p.Pro250Arg mutation (mean age 6.1 months), 10
      with TWIST-1 mutation (mean age7.6 months) and 14 patients with isolated
      bicoronal synostosis (mean age 6.1). RESULTS: We observed a significantly smaller
      FM area in FGFR3 group compared to control group and isolated brachycephaly group
      (p = 0.001 and p = 0.038, respectively). The mean FM area in FGFR3 group was
      426.13 mm(2) (p = 0.001), while in TWIST-1 group was 476.34 mm(2) (p = 0.103),
      and in isolated brachycephaly group 489.43 mm(2) (p = 0.129) compared to control
      group: 528.90 mm(2). The posterior segment of the sagittal diameter of the FM and
      its width as well as the bi-interoccipital synchondrosis diameters were
      significantly smaller in FGFR3 group compared to control group. In TWIST-1 group,
      the only altered dimension was the FM anterior segment of the sagittal diameter
      (p = 0.008). We did not observe any significant alteration of FM in patients with
      isolated brachycephaly compared to control group. DISCUSSION AND CONCLUSIONS: The
      FM area is significantly altered in FGFR3-related brachycephaly, whereas in
      patients with Saethre-Chotzen syndrome (TWIST-1 mutation) the mean FM area is
      similar to control group. This study confirms the importance of FGFRs on FM
      growth whereas TWIST-1 seems to have a minor role.

PMID- 24136084
TI  - Elevated blood urea nitrogen and medical outcome of psychiatric inpatients.
AB  - Elevated blood urea nitrogen (BUN) is associated with increased severity of
      illness and mortality, but its predictive value has not been studied in patients
      admitted to free-standing psychiatric hospitals. To determine the clinical
      outcome of psychiatric inpatients with elevated BUN on admission and to create a
      quantitative method of using BUN for predicting deteriorations requiring
      transfers of psychiatric inpatients to a general hospital we conducted a
      retrospective cohort study of 939 adults consecutively admitted to a free
      standing psychiatric hospital in 2010. Transfer to a general hospital was used as
      a proxy marker for poor medical outcome. The score Age (years) plus BUN (mg/dL)
      was used in sensitivity analyses to identify patients with medical deterioration
      in derivation (N = 523) and validation (N = 414) samples. Fifty-two (5.5%)
      patients had admission azotemia (BUN >25 mg/dL). Medical deteriorations requiring
      emergency transfer to a general hospital occurred in 24 (46.2%; 95% confidence
      interval = 32.6-49.8%) of azotemic patients and 112 (12.6%; 95% confidence
      interval = 10.4-14.8%) of those with normal BUN (p < 0.0001). Age + BUN >= 90
      identified 51 transferred patients and had positive and negative predictive
      values of 39.8 and 89.5%, respectively, in the entire sample. We conclude that
      psychiatric inpatients with BUN >25 mg/dL or Age + BUN >= 90 are at risk for
      medical deterioration. Free-standing psychiatric hospitals should develop models
      of care requiring frequent, scheduled medical follow-up and enhanced monitoring
      for this vulnerable populations.

PMID- 24136085
TI  - Treatment modality preferences and adherence to group treatment for panic
      disorder with agoraphobia.
AB  - To examine the relationship between preference for group psychotherapy and
      adherence to group cognitive-behavioral therapy (CBT) for clients with panic
      disorder with agoraphobia (PDA), 109 participants experiencing PDA completed a
      questionnaire measuring preference for group treatment (PGTQ) before beginning
      CBT groups. A t test was used to compare preference scores for group treatment to
      investigate whether participants who completed treatment differed from those who
      abandoned treatment. Participants who completed group therapy expressed higher
      preference for group treatment than participants who dropped out of treatment
      (t[107] = 1.99; p < 0.05). The PGTQ-4 presented adequate psychometric properties.
      Reliability analyses of the items retained after factorization demonstrated an
      acceptable level of internal consistency (Cronbach's alpha of 0.76). Preference
      for individual or group therapy appears to impact treatment retention for
      patients with PDA. Matching patients' preferences to the type of treatment
      modality used appears to be pertinent, especially for the treatment of anxiety
      disorders. In terms of practical implications, the rationale and benefits of
      group therapy should be explained to participants reluctant to engage in group
      therapy. Individual intervention or a combination of group and individual
      treatment could be considered for clients who are likely to drop out of group
      therapy. 

PMID- 24136086
TI  - Disposition and metabolism of safinamide, a novel drug for Parkinson's disease,
      in healthy male volunteers.
AB  - BACKGROUND/AIMS: Absorption, biotransformation and elimination of safinamide, an
      enantiomeric alpha-aminoamide derivative developed as an add-on therapy for
      Parkinson's disease patients, were studied in healthy volunteers administered a
      single oral dose of 400 mg (14)C safinamide methanesulphonate, labelled in
      metabolically stable positions. METHODS: Pharmacokinetics of the parent compound
      were investigated up to 96 h, of (14)C radioactivity up to 192/200 h post-dose.
      RESULTS/CONCLUSIONS: Maximum concentration was achieved at 1 h (plasma, median
      Tmax) for parent drug and at 7 and 1.5 h for plasma and whole blood (14)C
      radioactivity, respectively. Terminal half-lives were about 22 h for unchanged
      safinamide and 80 h for radioactivity. Safinamide deaminated acid and the N
      dealkylated acid were identified as major metabolites in urine and plasma. In
      urine, the beta-glucuronide of the N-dealkylated acid and the monohydroxy
      safinamide were also characterized. In addition, the glycine conjugate of the N
      dealkylated acid and 2-[4-hydroxybenzylamino]propanamide were tentatively
      identified as minor urinary metabolites.

PMID- 24136087
TI  - Rebuttal from Mr Shepherd et al.

PMID- 24136089
TI  - In silico models for designing and discovering novel anticancer peptides.
AB  - Use of therapeutic peptides in cancer therapy has been receiving considerable
      attention in the recent years. Present study describes the development of
      computational models for predicting and discovering novel anticancer peptides.
      Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at
      various positions in anticancer peptides. Support vector machine models were
      developed using amino acid composition and binary profiles as input features on
      main dataset that contains experimentally validated anticancer peptides and
      random peptides derived from SwissProt database. In addition, models were
      developed on alternate dataset that contains antimicrobial peptides instead of
      random peptides. Binary profiles-based model achieved maximum accuracy 91.44%
      with MCC 0.83. We have developed a webserver, which would be helpful in: (i)
      predicting minimum mutations required for improving anticancer potency; (ii)
      virtual screening of peptides for discovering novel anticancer peptides, and
      (iii) scanning natural proteins for identification of anticancer peptides
      (http://crdd.osdd.net/raghava/anticp/). 

PMID- 24136088
TI  - Advances in the nutritional and pharmacological management of phenylketonuria.
AB  - PURPOSE OF REVIEW: The purpose is to discuss advances in the nutritional and
      pharmacological management of phenylketonuria (PKU). RECENT FINDINGS:
      Glycomacropeptide (GMP), a whey protein produced during cheese production, is a
      low-phenylalanine (phe) intact protein that represents a new dietary alternative
      to synthetic amino acids for people with PKU. Skeletal fragility is a long-term
      complication of PKU that based on murine research, appears to result from both
      genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated
      with the GMP diet, compared with an amino acid diet, allowing greater radial bone
      growth. Pharmacologic therapy with tetrahydrobiopterin, acting as a molecular
      chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in
      some individuals. Large neutral amino acids inhibit phe transport across the
      intestinal mucosa and blood-brain barrier, and are most effective for individuals
      unable to comply with the low-phe diet. SUMMARY: Although a low-phe synthetic
      amino acid diet remains the mainstay of PKU management, new nutritional and
      pharmacological treatment options offer alternative approaches to maintain
      lifelong low phe concentrations. GMP medical foods provide an alternative to
      amino acid formula that may improve bone health, and tetrahydrobiopterin permits
      some individuals with PKU to increase tolerance to dietary phe. Further research
      is needed to characterize the long-term efficacy of these new approaches for PKU
      management.

PMID- 24136090
TI  - Fidaxomicin: a review of its use in patients with Clostridium difficile
      infection.
AB  - Oral fidaxomicin (Dificid((r)); Dificlir((r))) is a first-in-class macrocyclic
      antibacterial that is approved in several countries for the treatment of adult
      patients with Clostridium difficile-associated diarrhoea. Fidaxomicin 200 mg
      twice daily for 10 days was an effective and generally well tolerated treatment
      in adult patients with a first episode or first recurrence of C. difficile
      infection. In two multinational phase III trials, fidaxomicin treatment was
      noninferior to vancomycin treatment with regard to clinical cure rates and was
      associated with statistically significantly lower C. difficile infection
      recurrence rates and statistically significantly higher global cure rates than
      vancomycin. The drug has a favourable pharmacological profile, including having a
      narrow spectrum of activity that targets relevant pathogens, minimal impact on
      normal faecal microflora, a convenient treatment regimen and attainment of very
      high faecal concentrations. Albeit further clinical experience is required to
      fully define the position of fidaxomicin, it is a valuable emerging option for
      the treatment of first episode and recurrent episodes of C. difficile-associated
      diarrhoea.

PMID- 24136091
TI  - Cardiometabolic risk in adolescents: associations with physical activity,
      fitness, and sleep--in response to Kawada.

PMID- 24136093
TI  - Medication adherence, depression and the ongoing interpersonal context: a comment
      on Kronish et al.

PMID- 24136092
TI  - Structural stigma and cigarette smoking in a prospective cohort study of sexual
      minority and heterosexual youth.
AB  - BACKGROUND: Sexual minority youth are more likely to smoke cigarettes than
      heterosexuals, but research into the determinants of these disparities is
      lacking. PURPOSE: This study aimed to examine whether exposure to structural
      stigma predicts cigarette smoking in sexual minority youth. METHODS: Prospective
      data from adolescents participating in the Growing Up Today Study (2000-2005)
      were utilized. RESULTS: Among sexual minority youth, living in low structural
      stigma states (e.g., states with non-discrimination policies inclusive of sexual
      orientation) was associated with a lower risk of cigarette smoking after
      adjustment for individual-level risk factors (relative risk [RR] = 0.97; 95 %
      confidence interval [CI], 0.96, 0.99; p = 0.02). This association was marginally
      significant after additional controls for potential state-level confounders (RR =
      0.97; 95 % CI, 0.93, 1.00; p = 0.06). In contrast, among heterosexual youth,
      structural stigma was not associated with past-year smoking rates, documenting
      specificity of these effects to sexual minority youth. CONCLUSIONS: Structural
      stigma represents a potential risk factor for cigarette smoking among sexual
      minority adolescents.

PMID- 24136094
TI  - Is there a weekend bias in clutch-initiation dates from citizen science?
      Implications for studies of avian breeding phenology.
AB  - Accurate phenology data, such as the timing of migration and reproduction, is
      important for understanding how climate change influences birds. Given
      contradictory findings among localized studies regarding mismatches in timing of
      reproduction and peak food supply, broader-scale information is needed to
      understand how whole species respond to environmental change. Citizen science
      participation of the public in genuine research-increases the geographic scale of
      research. Recent studies, however, showed weekend bias in reported first-arrival
      dates for migratory songbirds in databases created by citizen-science projects. I
      investigated whether weekend bias existed for clutch-initiation dates for common
      species in US citizen-science projects. Participants visited nests on Saturdays
      more frequently than other days. When participants visited nests during the
      laying stage, biased timing of visits did not translate into bias in estimated
      clutch-initiation dates, based on back-dating with the assumption of one egg laid
      per day. Participants, however, only visited nests during the laying stage for
      25% of attempts of cup-nesting species and 58% of attempts in nest boxes. In some
      years, in lieu of visit data, participants provided their own estimates of clutch
      initiation dates and were asked "did you visit the nest during the laying
      period?" Those participants who answered the question provided estimates of
      clutch-initiation dates with no day-of-week bias, irrespective of their answer.
      Those who did not answer the question were more likely to estimate clutch
      initiation on a Saturday. Data from citizen-science projects are useful in
      phenological studies when temporal biases can be checked and corrected through
      protocols and/or analytical methods.

PMID- 24136096
TI  - Chemical safety, health care costs and the Affordable Care Act.
AB  - On May 22, 2013, the late Senator Frank Lautenberg (D-NJ), Senator David Vitter
      (R-LA) and 19 of their colleagues introduced bipartisan chemical safety
      legislation in the US Senate, "The Chemical Safety Improvement Act of 2013." The
      bill's purpose is to protect human health and the environment against the hazards
      of toxic chemicals, by requiring the US Environmental Protection Agency (EPA) to
      examine the safety of all chemicals in consumer products. The bill is currently
      before the Senate Committee on Environment and Public Works, chaired by Senator
      Barbara Boxer (D-CA). This legislation is critically important for physicians and
      healthcare organizations because it creates significant new opportunities to
      prevent disease and cut healthcare costs.

PMID- 24136097
TI  - Knowledge, experiences, and attitudes of medical students in Rome about
      tuberculosis.
AB  - BACKGROUND: Tuberculosis is the second leading cause of death from infectious
      disease. Insufficient knowledge among doctors about tuberculosis is one of the
      reasons for the increased tuberculosis rates in several low-endemic countries.
      The purpose of this study was to assess knowledge, experience, and attitude about
      tuberculosis among medical students. MATERIAL AND METHODS: After a pilot study, a
      cross-sectional survey was performed on fifth-year medical students at the
      Catholic University of Rome (Italy), using a self-administered questionnaire on
      attitude, experience and knowledge about epidemiology, diagnosis, and treatment
      of tuberculosis. The t test and multivariable linear regression analysis were
      performed to estimate the association between TB knowledge and investigated
      variables. RESULTS: Among 220 fifth-year medical students, the response rate was
      83.1%. The mean percentage of correct answers was 56.6% (63.5% for epidemiology
      and prevention, 54.1% for diagnosis, and 45.7% for treatment). Associations
      between internships in wards and greater knowledge of tuberculosis diagnosis
      (55.9% vs. 51.6%, p=0.02), treatment (48.4% vs. 41.8%, p=0.03) and total score
      (58.1% vs. 54.5%, p=0.04) were found. Students who reported receiving the Mantoux
      test had higher knowledge of tuberculosis epidemiology and prevention (65.4% vs.
      53.3%, p=0.001), diagnosis (55.2% vs. 48.3%, p=0.005), and total score (58.0% vs.
      49.1%, p=0.001). Students who had observed at least 1 active pulmonary
      tuberculosis case had a higher percentage of correct answers about diagnosis
      (55.5% vs. 51.4%, p=0.03) and total score (57.9% vs. 54.0%, p=0.03). The
      multivariable linear regression confirmed the association between higher
      knowledge and receiving the Mantoux test (beta coefficient=7.2; 95% CI 2.6-11.7),
      as well as having observed at least 1 X-ray of a TB patient (beta
      coefficient=5.3; 95% CI 1.0-9.7). CONCLUSIONS: A moderate level of general
      knowledge about tuberculosis was found, which suggests the need to modify current
      programs of infectious diseases in the curriculum of medical schools.

PMID- 24136098
TI  - Superior catalytic activity of nitrogen-doped graphene cathodes for high energy
      capacity sodium-air batteries.
AB  - Nitrogen-doped graphene nanosheets (N-GNSs) displayed a discharge capacity two
      times greater than their pristine counterpart, as well as superior
      electrocatalytic activity as a cathode material for sodium-air batteries. The
      enhanced performance of N-GNSs is attributed to the active sites introduced by
      nitrogen doping. 

PMID- 24136099
TI  - Shared decision making in dermato-oncology: preference for involvement of
      melanoma patients.
AB  - Increasing importance is being conferred to the implementation of shared decision
      making (SDM) in clinical practice for medical, ethical, and sociological reasons.
      In Germany, SDM has recently been adopted as an explicit goal in the S3-melanoma
      treatment guideline. The aim of this study is to present data on how melanoma
      patients want to be involved in treatment decisions and second on the dynamic of
      these preferences for involvement. This was investigated in consecutively
      recruited melanoma patients (stages I-III) in two German Skin Cancer Centers as
      part of a longitudinal questionnaire study. The Control Preference Scale assessed
      patients' preferences at baseline (n=405) and was readministered 1 year later
      (n=314) to detect potential changes. In addition, the perceived realization of
      SDM in the adjuvant interferon-alpha treatment decision was investigated in a
      subgroup of patients (n=108) using the nine-item Shared Decision Making
      Questionnaire (SDM-Q-9). More than 80% of the patients want to play an active
      role (autonomous or collaborative) in treatment decisions and only 17% want to
      delegate their decision to the doctor. We found a significant preference shift
      within a year in 43% of the patients, predominantly toward more active
      involvement. The results of the SDM-Q-9 indicate a moderate degree of perceived
      participation, with differing perceived implementation of the individual the SDM
      process steps. With the majority of melanoma patients preferring an active role
      in treatment decisions and improvable implementation of the SDM process steps in
      clinical practice, our findings support the relevance of SDM in dermato-oncology.

PMID- 24136100
TI  - The mouse retina in 3D: quantification of vascular growth and remodeling.
AB  - The mouse retina has become a prominent model for studying angiogenesis. The easy
      access and well-known developmental progression have significantly propelled our
      ability to examine and manipulate blood vessels in vivo. Nonetheless, most
      studies have restricted their evaluations to the superficial plexus (an upper
      vascular layer in contact with the vitreous). Here we present experimental data
      and quantification for the developmental progression of the full retina including
      the intermediate and deeper plexus that sprouts from the superficial layer. We
      analyze the origin and advancement of vertical sprouting and present the
      progression of vascular perfusion within the tissue. Furthermore, we introduce
      the use of Minkowsky functionals to quantify remodeling in the superficial and
      deeper plexus. The work expands information on the retina towards a 3D structure.
      This is of particular interest, as recent data have demonstrated differential
      effects of gene deletion on the upper and deeper plexus, highlighting the concept
      of distinct operational pathways during sprouting angiogenesis. 

PMID- 24136101
TI  - Gender-specific hip fracture risk in community-dwelling and institutionalized
      seniors age 65 years and older.
AB  - In this study of acute hip fracture patients, we show that hip fracture rates
      differ by gender between community-dwelling seniors and seniors residing in
      nursing homes. While women have a significantly higher rate of hip fracture among
      the community-dwelling seniors, men have a significantly higher rate among
      nursing home residents. INTRODUCTION: Differences in gender-specific hip fracture
      risk between community-dwelling and institutionalized seniors have not been well
      established, and seasonality of hip fracture risk has been controversial.
      METHODS: We analyzed detailed data from 1,084 hip fracture patients age 65 years
      and older admitted to one large hospital center in Zurich, Switzerland. In a
      sensitivity analysis, we extend to de-personalized data from 1,265 hip fracture
      patients from the other two large hospital centers in Zurich within the same time
      frame (total n = 2,349). The denominators were person-times accumulated by the
      Zurich population in the corresponding age/gender/type of dwelling stratum in
      each calendar season for the period of the study. RESULTS: In the primary
      analysis of 1,084 hip fracture patients (mean age 85.1 years; 78% women): Among
      community-dwelling seniors, the risk of hip fracture was twofold higher among
      women compared with men (RR = 2.16; 95% CI, 1.74-2.69) independent of age,
      season, number of comorbidities, and cognitive function; among institutionalized
      seniors, the risk of hip fracture was 26% lower among women compared with men (RR
      = 0.77; 95% CI: 0.63-0.95) adjusting for the same confounders. In the sensitivity
      analysis of 2,349 hip fracture patients (mean age 85.0 years, 76% women), this
      pattern remained largely unchanged. There is no seasonal swing in hip fracture
      incidence. CONCLUSION: We confirm for seniors living in the community that women
      have a higher risk of hip fracture than men. However, among institutionalized
      seniors, men are at higher risk for hip fracture.

PMID- 24136102
TI  - Relative influence of heritability, environment and genetics on serum sclerostin.
AB  - SUMMARY: We determined factors associated with serum sclerostin in 446 Afro
      Caribbean family members. Age, weight, sex, diabetes and kidney function were
      associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST
      gene region were associated with sclerostin. Variation in serum sclerostin is a
      heritable factor that is determined by both genetic and environmental factors.
      INTRODUCTION: Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that
      regulates bone mineralization and is a candidate gene locus for osteoporosis.
      However, little is known about the genetic and non-genetic sources of inter
      individual variation in serum sclerostin levels. METHODS: Serum sclerostin was
      measured in 446 Afro-Caribbean men and women aged 18+ from seven large,
      multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty
      six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb
      region encompassing the gene encoding sclerostin (SOST). Genetic and non-genetic
      factors were tested for association with serum sclerostin. RESULTS: Mean serum
      sclerostin was 41.3 pmol/l and was greater in men than in women (P < 0.05).
      Factors associated with higher serum sclerostin were increased age and body
      weight, male sex, diabetes and decreased glomerular filtration rate, which
      collectively accounted for 25.4 % of its variation. Residual genetic heritability
      of serum sclerostin was 0.393 (P < 0.0001). Nine SNPs reached nominal
      significance with sclerostin. Three of those nine SNPs represented independent
      association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8
      % of the phenotypic variation in sclerostin, although none of these SNPs
      surpassed a Bonferroni correction for multiple comparisons. CONCLUSIONS: Serum
      sclerostin is a heritable trait that is also determined by environmental factors
      including age, sex, adiposity, diabetes and kidney function. Three independent
      common SNPs within the SOST region may collectively account for a significant
      proportion of the variation in serum sclerostin.

PMID- 24136103
TI  - Long-term fracture rates seen with continued ibandronate treatment: pooled
      analysis of DIVA and MOBILE long-term extension studies.
AB  - Ibandronate reduces the risk of vertebral and non-vertebral fractures versus
      placebo in postmenopausal women with osteoporosis. This analysis, in which
      fractures were reported as safety events, showed that long-term use of
      ibandronate was associated with low fracture rates over 5 years of treatment.
      INTRODUCTION: A previous post-hoc meta-analysis of 2-3 year studies found that
      ibandronate regimens with annual cumulative exposure (ACE) of >=10.8 mg reduced
      the risk of vertebral and nonvertebral fractures (NVFs) versus placebo in
      postmenopausal women. This post-hoc analysis used individual patient data from
      the 2-year monthly oral ibandronate in ladies (MOBILE) and dosing intravenous
      administration (DIVA) studies, including the 3-year long-term extensions (LTEs),
      to assess fracture risk in patients treated with ibandronate for 5 years.
      METHODS: Patients treated for 2 years in MOBILE with monthly oral ibandronate 150
      mg (n = 176) and in DIVA with IV ibandronate every 2 months 2 mg (n = 253) or
      quarterly 3 mg (n = 263) who continued on the same regimens for 3 additional
      years in the LTEs were included. Three-year placebo data (n = 1,924) were
      obtained from the ibandronate osteoporosis vertebral fracture trial in North
      America and Europe (BONE) and IV Fracture Prevention trials. The primary endpoint
      was clinical fracture rate; clinical fracture data were collected as adverse
      events. Time to fracture was analyzed using Kaplan-Meier and statistical analysis
      was conducted using the log-rank test. All clinical fractures included all NVFs
      and symptomatic vertebral fractures. RESULTS: For ibandronate regimens with ACE
      >=10.8 mg, time to fracture was significantly longer for all clinical fractures,
      NVFs, and clinical vertebral fractures versus placebo (P = 0.005). For all
      fracture types, the rate of fracture appeared stable during the 5-year treatment
      period. CONCLUSION: In women with postmenopausal osteoporosis, continuous
      treatment with ibandronate over 5 years results in low sustained clinical
      fracture rate.

PMID- 24136104
TI  - Maternal vitamin D status in pregnancy and offspring brain development: the
      forgotten (but essential) needs of vitamin D era.

PMID- 24136105
TI  - Maternal vitamin D status in pregnancy and offspring brain development: authors'
      reply to C. Annweiler and O. Beauchet.

PMID- 24136106
TI  - Diffuse osteosclerosis in a patient with prostate cancer.
AB  - A 61-year-old man was referred to our outpatient clinic because of severe
      bilateral upper leg pain for 1 year. On admission, the patient had anemia and a
      high serum alkaline phosphatase level. Lumbar and femoral neck T-scores were
      +10.5 and +9.6, respectively. His radius 33 % T-score was -2.8. Plain radiographs
      of the patient's pelvis, spine, and long bones revealed osteosclerosis. The
      patient had previously undergone a prostate biopsy, which showed prostate
      adenocarcinoma (Gleason score 3 + 4). The patient's total and free prostate
      specific antigen were very high. According to previous records, the patient did
      not have anemia, and his serum alkaline phosphatase (ALP) level was normal. An
      abdominal radiograph taken 2 years earlier revealed a normal spine and pelvic
      bone. Bone scintigraphy yielded nontypical findings for prostate cancer
      metastasis. Computed tomography of the patient's thorax and abdomen showed
      heterogeneous sclerotic areas in all bones consistent with prostate cancer
      metastasis. A bone marrow biopsy disclosed disseminated carcinomatosis of bone
      marrow in association with prostate cancer. Clinicians should be aware of the
      possibility of prostate malignancy as a cause of high bone mineral density (BMD),
      even in the absence of typical localized findings on plain radiographs.

PMID- 24136107
TI  - Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes
      of different phenotypes in chronic obstructive pulmonary disease patients.
AB  - Peripheral muscle dysfunction, associated with reductions in fiber cross
      sectional area (CSA) and in type I fibers, is a key outcome in chronic
      obstructive pulmonary disease (COPD). However, COPD peripheral muscle function
      and structure show great heterogeneity, overlapping those in sedentary healthy
      subjects (SHS). While discrepancies in the link between muscle structure and
      phenotype remain unexplained, we tested whether the fiber CSA and the type I
      fiber reductions were the attributes of different phenotypes of the disease,
      using unsupervised clustering method and post hoc validation. Principal component
      analysis performed on functional and histomorphological parameters in 64 COPD
      patients {forced expiratory volume in 1 s (FEV1) = 42.0 [30.0-58.5]% predicted}
      and 27 SHS (FEV1 = 105.0 [95.0-114.0]% predicted) revealed two COPD clusters with
      distinct peripheral muscle dysfunctions. These two clusters had different type I
      fiber proportion (26.0 +/- 14.0% vs. 39.8 +/- 12.6%; P < 0.05), and fiber CSA
      (3,731 +/- 1,233 vs. 5,657 +/- 1,098 MUm(2); P < 0.05). The "atrophic" cluster
      showed an increase in muscle protein carbonylation (131.5 [83.6-200.3] vs. 83.0
      [68.3-105.1]; P < 0.05). Then, COPD patients underwent pulmonary rehabilitation.
      If the higher risk of exacerbations in the "atrophic" cluster did not reach
      statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P = 0.11,
      n = 54), the improvement of VO2sl after training was greater than in the
      nonatrophic cluster (+24 +/- 16% vs. +6 +/- 13%; P < 0.01). Last, their age was
      similar (60.4 +/- 8.8 vs. 60.8 +/- 9.0 yr; P = 0.87), suggesting a different time
      course of the disease. We identified and validated two phenotypes of COPD
      patients showing different muscle histomorphology and level of oxidative stress.
      Thus our study demonstrates that the muscle heterogeneity is the translation of
      different phenotypes of the disease. 

PMID- 24136108
TI  - Tibialis anterior muscle fascicle dynamics adequately represent postural sway
      during standing balance.
AB  - To maintain a stable, upright posture, the central nervous system (CNS) must
      integrate sensory information from multiple sources and subsequently generate
      corrective torque about the ankle joint. Although proprioceptive information from
      the muscles that cross this joint has been shown to be vital in this process, the
      specific source of this information remains questionable. Recent research has
      been focused on the potential role of tibialis anterior (TA) muscle during
      standing, largely due to the lack of modulation of its activity throughout the
      sway cycle. Ten young, healthy subjects were asked to stand normally under
      varying conditions, for periods of 60 s. During these trials, intramuscular
      electromyographic (EMG) activity and the fascicle length of three distinct
      anatomical regions of TA were sampled synchronously with kinematic data regarding
      sway position. In the quiet standing conditions, TA muscle activity was
      unmodulated and fascicle length changes in each region were tightly coupled with
      changes in sway position. In the active sway condition, more EMG activity was
      observed in TA and the fascicle length changes were decoupled from sway position.
      No regional specific differences in correlation values were observed, contrasting
      previous observations. The ability of the fascicles to follow sway position
      builds upon the suggestion that TA is well placed to provide accurate,
      straightforward sensory information to the CNS. As previously suggested, through
      reciprocal inhibition, afferent information from TA could help to regulate
      plantar flexor torque at relevant phases of the sway cycle. The proprioceptive
      role of TA appears to become complicated during more challenging conditions. 

PMID- 24136109
TI  - Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic
      anoxia.
AB  - In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)]
      in utero or at birth compromises anoxia-induced gasping and the recovery of heart
      rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean
      arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT
      content is unknown. We hypothesized that a loss of 5-HT for ~1 day would
      compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg
      ip) into rat pups (postnatal days 9-10 or 11-13, n = 22 treated, 24 control),
      causing a ~70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15
      anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In
      younger pups, we measured breathing frequency and tidal volume using "head-out"
      plethysmography and HR from the electrocardiogram. In older pups, we used whole
      body plethysmography to detect gasping, while monitoring MAP. Gasp latency and
      the time required for respiratory, HR, and MAP recovery following each episode
      were determined. Despite normal gasp latency, breathing frequency and a larger
      tidal volume (P < 0.001), 5-HT-deficient pups survived one-half the number of
      episodes as controls (P < 0.001). The anoxia-induced decrease in MAP experienced
      by 5-HT-deficient pups was double that of controls (P = 0.017), despite the same
      drop in HR (P = 0.48). MAP recovery was delayed ~10 s by 5-HT deficiency (P =
      0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced,
      premature loss of MAP in response to episodic anoxia. These data may help explain
      why some sudden infant death syndrome cases die from what appears to be
      cardiovascular collapse during apparent severe hypoxia. 

PMID- 24136110
TI  - A cross-validation of near-infrared spectroscopy measurements of skeletal muscle
      oxidative capacity with phosphorus magnetic resonance spectroscopy.
AB  - The purpose of this study was to cross-validate measurements of skeletal muscle
      oxidative capacity made with near-infrared spectroscopy (NIRS) measurements to
      those made with phosphorus magnetic resonance spectroscopy ((31)P-MRS). Sixteen
      young (age = 22.5 +/- 3.0 yr), healthy individuals were tested with both (31)P
      MRS and NIRS during a single testing session. The recovery rate of
      phosphocreatine was measured inside the bore of a 3-Tesla MRI scanner, after
      short-duration (~10 s) plantar flexion exercise as an index of skeletal muscle
      oxidative capacity. Using NIRS, the recovery rate of muscle oxygen consumption
      was also measured using repeated, transient arterial occlusions outside the MRI
      scanner, after short-duration (~10 s) plantar flexion exercise as another index
      of skeletal muscle oxidative capacity. The average recovery time constant was
      31.5 +/- 8.5 s for phosphocreatine and 31.5 +/- 8.9 s for muscle oxygen
      consumption for all participants (P = 0.709). (31)P-MRS time constants correlated
      well with NIRS time constants for both channel 1 (Pearson's r = 0.88, P < 0.0001)
      and channel 2 (Pearson's r = 0.95, P < 0.0001). Furthermore, both (31)P-MRS and
      NIRS exhibit good repeatability between trials (coefficient of variation = 8.1,
      6.9, and 7.9% for NIRS channel 1, NIRS channel 2, and (31)P-MRS, respectively).
      The good agreement between NIRS and (31)P-MRS indexes of skeletal muscle
      oxidative capacity suggest that NIRS is a valid method for assessing
      mitochondrial function, and that direct comparisons between NIRS and (31)P-MRS
      measurements may be possible. 

PMID- 24136111
TI  - The effect of interrupting prolonged sitting time with short, hourly, moderate
      intensity cycling bouts on cardiometabolic risk factors in healthy, young adults.
AB  - Although detrimental associations of sitting time and health indicators have been
      observed in young adults, evidence of pathophysiological mechanisms is lacking.
      Therefore, this study tested the hypothesis that the acute cardiometabolic
      effects of prolonged sitting can be compensated by hourly interruptions to
      sitting in healthy, young adults. Additionally, leg muscle activation during
      sitting and moderate-intensity physical activity interruptions was assessed.
      Eleven apparently healthy adults (18-24 yr; five men/six women) participated in
      this randomized, crossover study, involving two experimental conditions: 1) 8 h
      prolonged sitting and 2) 8 h of sitting, interrupted with hourly, 8-min, moderate
      intensity cycling exercise bouts. In both conditions, participants consumed two
      standardized, high-fat mixed meals after 1 and 5 h. Capillary blood samples were
      collected hourly during each 8-h experimental condition. Muscle activity was
      measured using electromyography. Muscle activity during cycling was seven to
      eight times higher compared with rest. Postprandial levels of C-peptide were
      significantly lower (unstandardized regression coefficient = -0.19; confidence
      interval = [-0.35; -0.03]; P = 0.017) during interrupted sitting compared with
      prolonged sitting. Postprandial levels of other cardiometabolic biomarkers (e.g.,
      glucose, triglycerides, cholesterol) were not significantly different between
      conditions. Hourly physical activity interruptions in sitting time, requiring a
      muscle activity of seven to eight times the resting value, led to an attenuation
      of postprandial C-peptide levels but not for other cardiometabolic biomarkers
      compared with prolonged sitting in healthy, young adults. Whether this acute
      effect transfers to chronic effects over time is unknown. 

PMID- 24136112
TI  - Separation of a functional deubiquitylating module from the SAGA complex by the
      proteasome regulatory particle.
AB  - Gene expression is an intricate process tightly linked from gene activation to
      the nuclear export of mRNA. Recent studies have indicated that the proteasome is
      essential for gene expression regulation. The proteasome regulatory particle
      binds to the SAGA complex and affects transcription in an ATP-dependent manner.
      Here we report that a specific interaction between the proteasomal ATPase, Rpt2p
      and Sgf73p of the SAGA complex leads to the dissociation of the H2Bub1
      deubiquitylating module (herein designated the Sgf73-DUBm) from SAGA both in
      vitro and in vivo. We show that the localization of the Sgf73-DUBm on chromatin
      is perturbed in rpt2-1, a strain of Saccharomyces cerevisiae that is specifically
      defective in the Rpt2p-Sgf73p interaction. The rpt2-1 mutant also exhibits
      impaired localization of the TREX-2 and MEX67-MTR2 complexes and is defective in
      mRNA export. Our findings collectively demonstrate that the proteasome-mediated
      remodelling of the SAGA complex is a prerequisite for proper mRNA export. 

PMID- 24136114
TI  - Stereospecific assignments in proteins using exact NOEs.
AB  - Recently developed methods to measure distances in proteins with high accuracy by
      "exact" nuclear Overhauser effects (eNOEs) make it possible to determine
      stereospecific assignments, which are particularly important to fully exploit the
      accuracy of the eNOE distance measurements. Stereospecific assignments are
      determined by comparing the eNOE-derived distances to protein structure bundles
      calculated without stereospecific assignments, or an independently determined
      crystal structure. The absolute and relative CYANA target function difference
      upon swapping the stereospecific assignment of a diastereotopic group yields the
      respective stereospecific assignment. We applied the method to the eNOE data set
      that has recently been obtained for the third immunoglobulin-binding domain of
      protein G (GB3). The 884 eNOEs provide relevant data for 47 of the total of 75
      diastereotopic groups. Stereospecific assignments could be established for 45
      diastereotopic groups (96 %) using the X-ray structure, or for 27 diastereotopic
      groups (57 %) using structures calculated with the eNOE data set without
      stereospecific assignments, all of which are in agreement with those determined
      previously. The latter case is relevant for structure determinations based on
      eNOEs. The accuracy of the eNOE distance measurements is crucial for making
      stereospecific assignments because applying the same method to the traditional
      NOE data set for GB3 with imprecise upper distance bounds yields only 13 correct
      stereospecific assignments using the X-ray structure or 2 correct stereospecific
      assignments using NMR structures calculated without stereospecific assignments.

PMID- 24136113
TI  - HIV/hepatitis C virus coinfection ameliorates the atherogenic lipoprotein
      abnormalities of HIV infection.
AB  - BACKGROUND: Higher levels of small low-density lipoprotein (LDL) and lower levels
      of high-density lipoprotein (HDL) subclasses have been associated with increased
      risk of cardiovascular disease. The extent to which HIV infection and
      HIV/hepatitis C virus (HCV) coinfection are associated with abnormalities of
      lipoprotein subclasses is unknown. METHODS: Lipoprotein subclasses were measured
      by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV
      infected and 5948 control participants in the Fat Redistribution and Metabolic
      Change in HIV Infection (FRAM), Coronary Artery Risk Development in Young Adults
      (CARDIA), and Multi-Ethnic Study of Atherosclerosis (MESA) studies. Multivariable
      regression was used to estimate the association of HIV and HIV/HCV coinfection
      with lipoprotein measures with adjustment for demographics, lifestyle factors,
      and waist-to-hip ratio. RESULTS: Relative to controls, small LDL levels were
      higher in HIV-monoinfected persons (+381 nmol/l, P <0.0001), with no increase
      seen in HIV/HCV coinfection (-16.6 nmol/l). Levels of large LDL levels were lower
      (-196 nmol/l, P <0.0001) and small HDL were higher (+8.2 MUmol/l, P < 0.0001) in
      HIV monoinfection with intermediate values seen in HIV/HCV coinfection. Large HDL
      levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70
      MUmol/l, P <0.0001), whereas little difference was seen in HIV-monoinfected
      persons (+0.33, P = 0.075). Within HIV-infected participants, HCV was associated
      independently with lower levels of small LDL (-329 nmol/l, P <0.0001) and small
      HDL (-4.6 MUmol/l, P <0.0001), even after adjusting for demographic and
      traditional cardiovascular risk factors. CONCLUSION: HIV-monoinfected
      participants had worse levels of atherogenic LDL lipoprotein subclasses compared
      with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering
      hepatic factors affecting lipoprotein production and/or metabolism. The effect of
      HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small
      subclasses remain to be determined.

PMID- 24136115
TI  - Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet
      activation via hydrolysis of talin.
AB  - Matrix metalloproteinase (MMP) activity is generally associated with normal or
      pathological extracellular processes such as tissue remodelling in growth and
      development or in tumor metastasis and angiogenesis. Platelets contain at least
      three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist
      induced platelet aggregation via extracellular signals. The non-selective Zn+2
      chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor,
      AEBSF, were found to inhibit all tested agonist-induced platelet aggregation
      reactions. In vitro analysis demonstrated that 1,10-phenanthroline completely
      inhibited MMP-1,2,and 9 but had little to no effect on calpain activity while the
      converse was true with AEBSF. We now demonstrate that MMP-2 functions
      intracellularly to regulate agonist-induced platelet aggregations via the
      hydrolytic activation of talin, the presumed final activating factor of
      glycoprotein (GP)IIb/IIIa integrin (the inside-out signal). Once activated
      GPIIb/IIIa binds the dimeric fibrinogen molecule required for platelet
      aggregation. The active intracellular MMP-2 molecule is complexed with JAK 2/STAT
      3, as demonstrated by the fact that all three proteins are co-immunoprecipitated
      with either anti-JAK 2, or anti-STAT 3 antibodies and by immunofluorescence
      studies. The MMP-2 platelet activation pathway can be synergistically inhibited
      with the non-selective MMP inhibitor, 1,10-phenanthroline, plus a JAK 2
      inhibitor. This activation pathway is distinct from the previously reported
      calpain-talin activating pathway. The identification of a new central pathway for
      platelet aggregation presents new potential targets for drug regulation and
      furthers our understanding of the complexity of platelet activation mechanisms. 

PMID- 24136117
TI  - Agreement between mathematically arterialised venous versus arterial blood gas
      values in patients undergoing non-invasive ventilation: a cohort study.
AB  - BACKGROUND: Blood gas analysis is important for assessment of ventilatory
      function. Traditionally, arterial analysis has been used. A method for
      mathematically arterialising venous blood gas values has been developed. Our aim
      was to validate this method in patients undergoing non-invasive ventilation (NIV)
      in an emergency department (ED). MATERIALS AND METHODS: This post hoc substudy of
      a prospective cohort study included adult patients undergoing NIV for acute
      respiratory compromise. When arterial blood gas analysis was required for
      clinical purposes, a venous sample was also drawn. Mathematically arterialised
      values were calculated independent of arterial values. Primary outcome of
      interest was agreement between mathematically arterialised venous and arterial
      values for pH and pCO2. Bland-Altman agreement plot analysis was used. RESULTS:
      Eighty sample-pairs (58 patients) were studied. Mean difference for arterial pH
      (actual-calculated) was 0.01 pH units (95% limits of agreement: -0.04, 0.06).
      Mean difference for pCO2 (actual-calculated) was -0.06 kPa (95% limits of
      agreement: -1.34, 1.22). CONCLUSIONS: For patients undergoing NIV in an ED,
      agreement between mathematically arterialised venous values and arterial values
      was close for pH but only moderate for pCO2. Depending on clinician tolerance for
      agreement, this method may be a clinically useful alternative to arterial blood
      gas analysis in the ED.

PMID- 24136118
TI  - A case-control study examining inconsistencies in pain management following
      fractured neck of femur: an inferior analgesia for the cognitively impaired.
AB  - Previous research suggests individuals who suffer from cognitive impairment are
      less able to vocalise pain than the rest of the cognitively-intact population.
      This feature of cognitive impairment may be leading to a chronic underdetection
      of pain as current assessment tools strongly rely on the participation of the
      patient. To explore inconsistencies in pain management within the acute setting,
      we conducted a retrospective assessment of 224 patients presenting with fractured
      neck of femur at a large teaching hospital's accident and emergency (A&E)
      department between 2 June 2011 and 2 June 2012. These patients were split into
      either a cognitively-impaired or cognitively-intact cohort based on their
      Abbreviated Mental Test Scores. Patients with cognitive impairment, on average,
      received a weaker level of analgesia than individuals without impairment both in
      the ambulance and in A&E. In the ambulance, 45% of cognitively-impaired patients
      were prescribed no pain relief compared with just 8% of those individuals who
      remain cognitively intact. After arrival at A&E, these inconsistencies continued
      with 69% of the cognitively-intact cohort receiving the strongest opioid
      analgesia compared with just 37% of the cognitively-impaired cohort. The
      cognitively-impaired cohort would also wait on average an hour longer before
      receiving this initial pain relief. We believe that these differences stem from
      cognitively-impaired patients being unable to vocalise their pain through
      traditional assessment methods. This work discusses the potential development or
      adoption of a tool which can be applied in the acute setting and relies less on
      vocalisation but more on the objective features of pain, so making it applicable
      to cognitively-impaired individuals.

PMID- 24136119
TI  - Simulation training based on observation with minimal participation improves
      paediatric emergency medicine knowledge, skills and confidence.
AB  - OBJECTIVE: Simulation is becoming standard during emergency medicine (EM)
      training. To determine if observation-based simulation with minimal participation
      improves knowledge, skill performance and confidence, we created and evaluated 12
      paediatric emergency medicine (PEM) simulations focusing on the educational value
      of observation. METHODS: Thirty-one EM residents participated in 1-2 simulations
      each and observed multiple others. Scores obtained on a knowledge test
      presimulation and postsimulation, clinical skills assessed for changes in
      performance over the course of the study, and confidence questionnaires given
      presimulation and postsimulation were analysed. Participants' feedback regarding
      the observation model was also evaluated. RESULTS: Average scores obtained on the
      knowledge test improved significantly presimulation to postsimulation (36.3% vs
      51.4%), and remained consistent postsimulation to 4 months after simulation
      training (51.4% vs 48.8%). Gain scores for participants who observed >80% of the
      simulations were significantly higher than for those who observed<80% (20.7% vs
      12.5%). Over 90% of skillsets reassessed throughout the simulations showed
      improvement, and residents assessed themselves as more confident after simulation
      training. All participants rated the training as very useful, and 71% reported
      that being observed was stressful but beneficial, as clinical emergencies are
      stressful as well. CONCLUSIONS: Using observation with minimal participation as
      the foundation of simulation training may lead to improvement in observer
      knowledge, skills and confidence. Observation-based simulation training may also
      save time and resources, allowing a broader coverage of clinical scenarios than
      programmes requiring active participation by all learners.

PMID- 24136120
TI  - Sudden pseudoproptosis.

PMID- 24136121
TI  - Authors' response.

PMID- 24136122
TI  - Log-rolling a blunt major trauma patient is inappropriate in the primary survey.

PMID- 24136123
TI  - An outcomes evaluation of an emergency department early pregnancy assessment
      service and early pregnancy assessment protocol.
AB  - BACKGROUND: Complications in early pregnancy, such as threatened or actual
      miscarriage is a common occurrence resulting in many women presenting to the
      emergency department (ED). Early pregnancy service delivery models described in
      the literature vary in terms of approach, setting and outcomes. Our objective was
      to determine outcomes of women who presented to an Australian regional ED with
      diagnoses consistent with early pregnancy complications following the
      implementation of an early pregnancy assessment service (EPAS) and early
      pregnancy assessment protocol (EPAP) in July 2011. METHODS: A descriptive,
      comparative (6 months before and after) study was undertaken. Data were extracted
      from the hospital ED information system and medical healthcare records. Outcome
      measures included: time to see a clinician, ED length of stay, admission rate, re
      presentation rate, hospital admission and types of pathology tests ordered.
      RESULTS: Over the 12 -month period, 584 ED presentations were made to the ED with
      complications of early pregnancy (268 PRE and 316 POST EPAS-EPAP). Outcomes that
      improved statistically and clinically following implementation included: time to
      see a clinician (decreased by 6 min from 35 to 29 min), admission rate (decreased
      6% from 14.5% to 8.5%), increase in beta-human chorionic gonadotrophin ordering
      by 10% (up to 80% POST), increase in ultrasound (USS) performed by 10% (up to 73%
      POST) and increase in pain score documentation by 23% (up to 36% POST).
      CONCLUSIONS: The results indicate that patient and service delivery improvements
      can be achieved following the implementation of targeted service delivery models
      such as EPAS and EPAP in the ED.

PMID- 24136125
TI  - Clinical outcome of redo operation on aortic root.
AB  - BACKGROUND: With the increasing use of biologic conduits or bioprosthetic valve,
      the number of patients who require redo operation on aortic root increased.
      METHODS: In the past 22 years, 14 patients underwent redo operation on aortic
      root. The mean age was 61.9 +/- 14.8 years. Previous operations were full root
      replacement with stentless valve (n = 4), aortic root replacement with
      subcoronary technique (n = 3) and Bentall operation (n = 7). The operation
      interval was 5.4 +/- 6.4 years. Indication for redo operation included structural
      valve deterioration (n = 6), prosthetic valve endocarditis (n = 4), perivalvular
      leakage (n = 2), dilatation of sinus of Valsalva (n = 1) and dehiscence of
      proximal anastomosis line (n = 1). Mean follow-up period was 5.3 +/- 5.2 years.
      RESULTS: Present operations were full root replacement with stentless valve (n =
      5) and Bentall operation (n = 9). There was one in-hospital death (7.1 %) caused
      by arrhythmia. Postoperative complications included implantation of permanent
      pacemaker (n = 3), arrhythmia (n = 2) and re-intubation (n = 1). The 5-year
      survival was 92.9 +/- 6.9%. Freedom from redo aortic operation at 5 years was
      100%. CONCLUSION: Redo operation on aortic root can be performed with acceptable
      in-hospital mortality and good late survival.

PMID- 24136126
TI  - Wearable motion sensors to continuously measure real-world physical activities.
AB  - PURPOSE OF REVIEW: Rehabilitation for sensorimotor impairments aims to improve
      daily activities, walking, exercise, and motor skills. Monitoring of practice and
      measuring outcomes, however, is usually restricted to laboratory-based procedures
      and self-reports. Mobile health devices may reverse these confounders of daily
      care and research trials. RECENT FINDINGS: Wearable, wireless motion sensor data,
      analyzed by activity pattern-recognition algorithms, can describe the type,
      quantity, and quality of mobility-related activities in the community. Data
      transmission from the sensors to a cell phone and the Internet enable continuous
      monitoring. Remote access to laboratory quality data about walking speed,
      duration and distance, gait asymmetry and smoothness of movements, as well as
      cycling, exercise, and skills practice, opens new opportunities to engage
      patients in progressive, personalized therapies with feedback about the
      performance. Clinical trial designs will be able to include remote verification
      of the integrity of complex physical interventions and compliance with practice,
      as well as capture repeated, ecologically sound, ratio scale outcome measures.
      SUMMARY: Given the progressively falling cost of miniaturized wearable
      gyroscopes, accelerometers, and other physiologic sensors, as well as inexpensive
      data transmission, sensing systems may become as ubiquitous as cell phones for
      healthcare. Neurorehabilitation can develop these mobile health platforms for
      daily care and clinical trials to improve exercise and fitness, skills learning,
      and physical functioning.

PMID- 24136127
TI  - Bioengineering solutions for neural repair and recovery in stroke.
AB  - PURPOSE OF REVIEW: This review discusses emerging bioengineering opportunities
      for the treatment of stroke and their potential to build on current
      rehabilitation protocols. RECENT FINDINGS: Bioengineering is a vast field that
      ranges from biomaterials to brain-computer interfaces. Biomaterials find
      application in the delivery of pharmacotherapies, as well as the emerging field
      of tissue engineering. For the treatment of stroke, these approaches have to be
      seen in the context of physical therapy in order to maximize functional outcomes.
      There is also an emergence of rehabilitation that engages engineering solutions,
      such as robot-assisted training, as well as brain-computer interfaces that can
      potentially assist in the case of paralysis. SUMMARY: Stroke remains the main
      cause of adult disability with rehabilitation therapy being the focus for chronic
      impairments. Bioengineering is offering new opportunities to both support and
      synergize with currently available treatment options, and also promises to
      potentially dramatically improve available approaches. VIDEO ABSTRACT AVAILABLE:
      See the Video Supplementary Digital Content 1 (http://links.lww.com/CONR/A21).

PMID- 24136128
TI  - Stem cell therapy for acute cerebral injury: what do we know and what will the
      future bring?
AB  - PURPOSE OF REVIEW: The central nervous system has limited capacity for
      regeneration after acute and chronic injury. An attractive approach to stimulate
      neural plasticity in the brain is to transplant stem cells in order to restore
      function. Here, we discuss potential mechanisms of action, current knowledge and
      future perspectives of clinical stem cell research for stroke and traumatic brain
      injury. RECENT FINDINGS: Preclinical data using various models suggest stem cell
      therapy to be a promising therapeutic avenue. Progress has been made in
      elucidating the mechanism of action of various cell types used, shifting the
      hypothesis from neural replacement to enhancing endogenous repair processes.
      Translation of these findings in clinical trials is currently being pursued with
      emphasis on both safety as well as efficacy. SUMMARY: Clinical trials are
      currently recruiting patients in phase I and II trials to gain more insight in
      the therapeutic potential of stem cells in acute cerebral injury. A close
      interplay between results of these clinical trials and more extensive basic
      research is essential for future trial design, choosing the optimal
      transplantation strategy and selecting the right patients.

PMID- 24136130
TI  - Generation of a head phantom according to the 95th percentile Chinese population
      data for evaluating the specific absorption rate by wireless communication
      devices.
AB  - A Chinese head phantom (CHP) is constructed for evaluating the specific
      absorption rate (SAR) by the wireless transceivers. The dimensions of the head
      phantom are within 4 % difference compared with the 95th percentile data from the
      China's standard. The shell's thickness and the configuration of the pinna are
      the same as those of the specific anthropomorphic mannequin (SAM). Three
      computable models for the mobile phones are generated and used in the SAR
      simulations with the SAM and the CHP. The results show that the simulated SAR
      from the SAM head is similar. Its morphological reason has been analysed. The
      authors discuss the conservativeness of the two head phantoms as well. The CHP
      can be used in the inter-laboratory evaluation for the SAR uncertainty. It can
      also provide the information for the SAR variability due to physical difference,
      which will benefit the maintenance and the harmonisation of the standards. 

PMID- 24136131
TI  - Technical note: false catastrophic age-at-death profiles in commingled bone
      deposits.
AB  - Age-at-death profiles obtained using the minimum number of individuals (MNI) for
      mass deposits of commingled human remains may be biased by over-representation of
      subadult individuals. A computer simulation designed in the R environment has
      shown that this effect may lead to misinterpretation of such samples even in
      cases where the completeness rate is relatively high. The simulation demonstrates
      that the use of the Most Likely Number of Individuals (MLNI) substantially
      reduces this bias.

PMID- 24136129
TI  - The interaction between training and plasticity in the poststroke brain.
AB  - PURPOSE OF REVIEW: Recovery after stroke can occur either via reductions in
      impairment or through compensation. Studies in humans and nonhuman animal models
      show that most recovery from impairment occurs in the first 1-3 months after
      stroke as a result of both spontaneous reorganization and increased
      responsiveness to enriched environments and training. Improvement from impairment
      is attributable to a short-lived sensitive period of postischemic plasticity
      defined by unique genetic, molecular, physiological, and structural events. In
      contrast, compensation can occur at any time after stroke. Here, we address both
      the biology of the brain's postischemic sensitive period and the difficult
      question of what kind of training (task-specific vs. a stimulating environment
      for self-initiated exploration of various natural behaviors) best exploits this
      period. RECENT FINDINGS: Data suggest that three important variables determine
      the degree of motor recovery from impairment: the timing, intensity, and approach
      to training with respect to stroke onset; the unique postischemic plasticity
      milieu; and the extent of cortical reorganization. SUMMARY: Future work will need
      to further characterize the unique interaction between types of training and
      postischemic plasticity, and find ways to augment and prolong the sensitive
      period using pharmacological agents or noninvasive brain stimulation.

PMID- 24136132
TI  - Synergism between propolis and hyperthermal intraperitoneal chemotherapy with
      cisplatin on ehrlich ascites tumor in mice.
AB  - We investigated antitumor, genotoxic, chemopreventive, and immunostimulative
      effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy
      (HIPEC) in a mouse-bearing Ehrlich ascites tumor (EAT). Mice were treated with
      water-soluble derivative of propolis (WSDP) at a dose of 50 mg kg(-1) , 7 and 3
      days before implantation of EAT cells, whereas cisplatin (5 or 10 mg kg(-1) ) was
      injected 3 days after implantation of EAT cells at 37 degrees C and 43 degrees C.
      The following variables were analyzed: the total number of cells, differential
      count of the cells present in the peritoneal cavity, functional activity of
      macrophages, comet assay, and micronucleus assay. The combination of WSDP + CIS 5
      mg kg(-1) at 37 degrees C resulted in tumor growth inhibition and increased the
      survival of mice by additional 115.25%. WSDP with HIPEC increased the survival of
      mice by additional 160.3% as compared with HIPEC. WSDP reduced cisplatin toxic
      and genotoxic effect to normal cells without affecting cisplatin cytotoxicity on
      EAT cells. In addition, WSDP with HIPEC increased the cytotoxic actions of
      macrophages to tumor cells. Water-soluble derivative of propolis increases
      macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin
      toxicity to normal cells.

PMID- 24136133
TI  - External validation of recombinant antigens for serodiagnosis of machine
      operator's lung.
AB  - BACKGROUND: Machine operator's lung (MOL) is a hypersensitivity pneumonitis the
      diagnosis of which is difficult. Our laboratory previously developed an ELISA
      test using recombinant antigens from Mycobacterium immunogenum isolated in French
      plant. The objective was to validate the previous ELISA results with ten new
      suspected cases from Germany. METHODS: Two serological analyses were performed:
      ELISA with the six recombinant antigens, and electrosyneresis with crude antigens
      of M. immunogenum and three other main species isolated from contaminated
      metalworking fluids. RESULTS: The two recombinant antigens acyl-CoA dehydrogenase
      and dihydrolipoyl dehydrogenase, combined together, and electrosyneresis are
      useful in making the diagnosis regardless of the clinical and radiological data.
      Finally 9 out of the 10 suspected cases were declared as MOL. CONCLUSIONS:
      Despite the geographical distance, the crude and recombinant antigens produced to
      investigate the clustered French cases also proved to be useful in diagnosing the
      suspected cases in Germany.

PMID- 24136134
TI  - Increased fundus autofluorescence related to outer retinal disruption.

PMID- 24136136
TI  - Ultrahigh capacitive performance from both Co(OH)2/graphene electrode and
      K3Fe(CN)6 electrolyte.
AB  - Pseudocapacitance is commonly associated to the reversible redox reactions from
      electrode materials, but the enhancement in pseudocapacitance that only relies on
      electrode materials is limited. Here, we explore the possibility of enhancing
      pseudocapacitance through both Co(OH)2/graphene nanosheets (GNS) electrode and
      K3Fe(CN)6 electrolyte. With a good conductivity and favoring electron transfer,
      GNS are hybridized with Co(OH)2 to improve the pseudocapacitance of Co(OH)2,
      including enhancing its rate capability and electrochemical stability. Adding
      K3Fe(CN)6 into KOH electrolyte further enhances the pseudocapacitance via both
      directly contributing pseudocapacitance to Co(OH)2/GNS and promoting the electron
      gain and loss of Co ions. This novel Co(OH)2/GNS-K3Fe(CN)6/KOH electrode system
      shows an ultrahigh specific capacitance of 7514 Fg-1 at 16 Ag-1 in mixed 1 M KOH
      and 0.08 M K3Fe(CN)6, more than 100% coulombic efficiency, and long-term cycling
      stability (the capacitance retention is 75% after 20000 continuous charge
      discharge cycles in mixed 1 M KOH and 0.04 M K3Fe(CN)6.

PMID- 24136137
TI  - Are acute post-resistance exercise increases in testosterone, growth hormone, and
      IGF-1 necessary to stimulate skeletal muscle anabolism and hypertrophy?

PMID- 24136138
TI  - Evidence of parasympathetic hyperactivity in functionally overreached athletes.
AB  - PURPOSE: We analyzed HR variability (HRV) to detect alterations in autonomic
      function that may be associated with functional overreaching (F-OR) in endurance
      athletes. METHODS: Twenty-one trained male triathletes were randomly assigned to
      either intensified training (n = 13) or normal training (n = 8) groups during 5
      wk. HRV measures were taken daily during a 1-wk moderate training (baseline), a 3
      wk overload training, and a 1-wk taper. RESULTS: All the subjects of the
      intensified training group demonstrated a decrease in maximal incremental running
      test performance at the end of the overload period (-9.0% +/- 2.1% of baseline
      value) followed by a performance supercompensation after the taper and were
      therefore diagnosed as F-OR. According to a qualitative statistical analysis
      method, a likely to very likely negative effect of F-OR on HR was observed at
      rest in supine and standing positions, using isolated seventh-day values and
      weekly average values, respectively. When considering the values obtained once
      per week, no clear effect of F-OR on HRV parameters was found. In contrast, the
      weekly mean of each HRV parameter showed a larger change in indices of
      parasympathetic tone in the F-OR group than the control group in supine position
      (with a 96%/4%/0% chance to demonstrate a positive/trivial/negative effect on Ln
      RMSSD after the overload period; 77%/22%/1% on LnHF) and standing position
      [98%/1%/1% on Ln RMSSD; 99%/0%/1% on LnHF; 95%/1%/4% on Ln(LF + HF)]. During the
      taper, theses responses were reversed. CONCLUSIONS: Using daily HRV recordings
      averaged over each week, this study detected a progressive increase in the
      parasympathetic modulation of HR in endurance athletes led to F-OR. It also
      revealed that due to a wide day-to-day variability, isolated, once per week HRV
      recordings may not detect training-induced autonomic modulations in F-OR
      athletes.

PMID- 24136139
TI  - Site-selective electronic correlation in alpha-plutonium metal.
AB  - An understanding of the phase diagram of elemental plutonium (Pu) must include
      both, the effects of the strong directional bonding and the high density of
      states of the Pu 5f electrons, as well as how that bonding weakens under the
      influence of strong electronic correlations. Here we present electronic-structure
      calculations of the full 16-atom per unit cell alpha-phase structure within the
      framework of density functional theory together with dynamical mean-field theory.
      Our calculations demonstrate that Pu atoms sitting on different sites within the
      alpha-Pu crystal structure have a strongly varying site dependence of the
      localization-delocalization correlation effects of their 5f electrons and a
      corresponding effect on the bonding and electronic properties of this complicated
      metal. In short, alpha-Pu has the capacity to simultaneously have multiple
      degrees of electron localization/delocalization of Pu 5f electrons within a pure
      single-element material. 

PMID- 24136140
TI  - Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional
      Advanced Head-and-Neck Squamous Cell Carcinoma.
AB  - PURPOSE: There is little published data on the technique and results of whole
      field (WF) sequential intensity-modulated radiotherapy (S-IMRT) for patients with
      head-and-neck squamous cell carcinoma (HNSCC). We report the treatment outcomes,
      adverse events (AEs), and dosimetric parameters in local-regional advanced (LRA)
      HNSCC patients treated with the WF S-IMRT technique. METHODS: The IRB approved
      this retrospective study. Patients received WF S-IMRT with or without concomitant
      chemotherapy. Three separate IMRT plans corresponding to 3 planning target
      volumes were generated. This study reports patient and tumor characteristics,
      treatment-induced acute AEs based on CTCAE version 3.0, chronic AEs according to
      RTOG scale and treatment outcomes, local-regional control (LRC), distant
      metastases (DM), relapse-free survival (RFS), and overall survival (OS). RESULTS:
      Between January 2003 and December 2010, 103 patients with LRA HNSCC were treated
      either definitively or postoperatively with WF S-IMRT, with (99 patients) or
      without (4 patients) concurrent chemotherapy. The median age was 55 years (range,
      30 to 89 y). The median cumulative target dose was 70 Gy (range, 60 to 75 Gy). At
      a median follow-up of 40 months (range, 4 to 95 mo), the 2- and 5-year rates of
      OS were 94% and 77%, RFS were 90% and 84%, LRC were 97% and 93%, and DM were 9%
      and 11%, respectively. Grade 3 acute AEs included mucositis (68%), dysphagia
      (35%), weight loss (19.6%), and xerostomia (7.8%). Chronic worst grade 3 AEs
      included xerostomia (21.9%), weight loss (12.8%), and dysphagia (12.5%). Chronic
      grade 3 AEs at last follow-up included weight loss (6.25%), dysphagia (6.2%), and
      xerostomia (6.2%). No patient had an acute or chronic grade 4 AE, brachial
      plexopathy, or spinal cord injury. CONCLUSIONS: WF S-IMRT results in excellent
      tumor control and an acceptable toxicity profile in LRA HNSCC patients treated
      with this technique.

PMID- 24136141
TI  - Outcomes of Definitive Radiation Therapy for Primary Vaginal Carcinoma.
AB  - OBJECTIVE(S): The aim of this study was to review treatment and outcomes of
      patients with primary vaginal cancer treated with definitive radiotherapy.
      MATERIALS AND METHODS: We retrospectively reviewed medical records of 71 patients
      with primary vaginal adenocarcinoma or squamous cell carcinoma treated with
      definitive radiotherapy with at least 2 years of follow-up (median follow-up,
      6.24 y). RESULTS: Ninety-three percent of patients were treated with external
      beam radiotherapy plus brachytherapy (median dose, 7540 cGy); 4 patients with
      stage I disease and 1 patient with stage II disease were treated with
      brachytherapy alone (median dose, 6000 cGy). The cause-specific 5- and 10-year
      survival rates, respectively, were 96% and 96% for stage I patients, 75% and 68%
      for stage II patients, 69% and 64% for stage III patients, and 53% and 53% for
      stage IVA patients. The 5- and 10-year local-regional control rates for all
      patients were 79% and 75%, respectively. The 5- and 10-year distant metastasis
      free survival rates for all patients were 87% and 85%, respectively. Sixteen
      patients had tumors involving the distal one third of the vagina. Of the 7 who
      received elective inguinal node irradiation, 0 failed in the inguinal nodes. Of
      the 9 who did not receive elective inguinal node irradiation, 2 failed in the
      inguinal nodes. Severe complications (grades 3 to 4) occurred in 16 patients
      (23%). CONCLUSIONS: Radiotherapy provides excellent results as definitive
      treatment for primary vaginal cancer, although the risk of severe complications
      is high. Generally, treatment should consist of both external-beam radiation
      therapy and brachytherapy. Inguinal nodes should be irradiated electively when
      the primary tumor involves the distal one third of the vagina.

PMID- 24136142
TI  - Retroperitoneal liposarcoma: a comprehensive review.
AB  - Retroperitoneal liposarcomas are rare mesenchymal tumors of the retroperitoneum
      that typically present with advanced disease and often carry a poor prognosis.
      Because of their rarity and anatomic location, these malignant tumors can cause a
      diagnostic dilemma and present several therapeutic challenges. They are usually
      associated with a high rate of recurrence despite grossly complete resection,
      thus requiring long-term and often indefinite follow-up. Relevant data on this
      topic was procured and synthesized with the aid of a comprehensive Medline search
      in addition to oncologic, pathologic, urologic, radiologic, and surgical
      literature review on retroperitoneal sarcomas. This article provides an in-depth
      review into the natural history, pathology, clinical manifestations, and
      prognostic features of retroperitoneal liposarcomas. It also discusses the
      reliability of diagnostic procedures and novel curative approaches that are
      currently being evaluated for the disease.

PMID- 24136143
TI  - Gene expression profiling of Pseudomonas putida F1 after exposure to aromatic
      hydrocarbon in soil by using proteome analysis.
AB  - Pseudomonas putida F1 can metabolize toluene, ethylbenzene, and benzene for
      growth. Previously, we identified proteins involved in the utilization of these
      compounds by P. putida F1 through culture in liquid media. However, it was
      unclear whether laboratory analysis of bacterial activity and catabolism
      accurately reflected the soil environment. We identified proteins involved in the
      degradation of toluene, ethylbenzene, and benzene growth in soil using two
      dimensional gel electrophoresis (2-DE) or standard SDS-PAGE combined with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). According to 2-DE/LC-MS/MS
      analysis, 12 of 22 key enzymes involved in the degradation of toluene,
      ethylbenzene, and benzene were detected. In standard SDS-PAGE/LC-MS/MS analysis
      of soil with ethylbenzene, approximately 1,260 cellular proteins were identified
      in P. putida F1. All key enzymes and transporter and sensor proteins involved in
      ethylbenzene degradation were up-regulated similar to that noted in liquid
      cultures. In P. putida F1, aromatic hydrocarbon response in soil is the same as
      that observed in liquid media. 

PMID- 24136144
TI  - Intracellular photoactivation of caged cGMP induces myosin II and actin responses
      in motile cells.
AB  - Cyclic GMP (cGMP) is a ubiquitous second messenger in eukaryotic cells. It is
      assumed to regulate the association of myosin II with the cytoskeleton of motile
      cells. When cells of the social amoeba Dictyostelium discoideum are exposed to
      chemoattractants or to increased osmotic stress, intracellular cGMP levels rise,
      preceding the accumulation of myosin II in the cell cortex. To directly
      investigate the impact of intracellular cGMP on cytoskeletal dynamics in a living
      cell, we released cGMP inside the cell by laser-induced photo-cleavage of a caged
      precursor. With this approach, we could directly show in a live cell experiment
      that an increase in intracellular cGMP indeed induces myosin II to accumulate in
      the cortex. Unexpectedly, we observed for the first time that also the amount of
      filamentous actin in the cell cortex increases upon a rise in the cGMP
      concentration, independently of cAMP receptor activation and signaling. We
      discuss our results in the light of recent work on the cGMP signaling pathway and
      suggest possible links between cGMP signaling and the actin system. 

PMID- 24136145
TI  - Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of
      cutaneous T-cell lymphoma.
AB  - BACKGROUND: Both gemcitabine and bexarotene are established single agents for the
      treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility
      and efficacy of combining these drugs in a single-arm phase II study. METHODS:
      Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy
      and at least one prior systemic therapy were given four cycles of gemcitabine and
      concurrent bexarotene for 12 weeks. Responders were continued on bexarotene
      maintenance until disease progression or unacceptable toxicity. RESULTS: The
      median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage
      III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were
      B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients
      completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a
      reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although
      the objective disease response rate at 12 weeks was 31% (partial response (PR)
      31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease
      (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and
      median overall survival was 21.2 months. CONCLUSION: The overall response rate of
      the combination did not reach the specified target to proceed further and is
      lower than that previously reported for gemcitabine as a single agent.

PMID- 24136146
TI  - Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer.
AB  - BACKGROUND: Biliary tract cancers (BTC) are relatively rare malignant tumours
      with poor prognosis. It is known from other solid neoplasms that antitumour
      inflammatory response has an impact on tumour behaviour and patient outcome. The
      aim of this study was to provide a comprehensive characterisation of antitumour
      inflammatory response in human BTC. METHODS: Tumour-infiltrating T lymphocytes
      (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes
      (CD20+), macrophages (CD68+) as well as mast cells (CD117+) were assessed by
      immunohistochemistry in 375 BTC including extrahepatic (ECC; n=157), intrahepatic
      (ICC; n=149), and gallbladder (GBAC; n=69) adenocarcinomas. Overall and
      intraepithelial quantity of tumour-infiltrating immune cells was analysed. Data
      were correlated with clinicopathological variables and patient survival. RESULTS:
      The most prevalent inflammatory cell type in BTC was the T lymphocyte. Components
      of the adaptive immune response decreased, whereas innate immune response
      components increased significantly in the biliary intraepithelial neoplasia -
      primary carcinoma - metastasis sequence. BTC patients with intraepithelial tumour
      infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes showed a significantly longer
      overall survival. Number of total intraepithelial tumour-infiltrating Foxp3+
      regulatory T lymphocytes (HR: 0.492, P=0.002) and CD4+ T lymphocytes (HR: 0.595,
      P=0.008) were tumour grade- and UICC-stage-independent prognosticators. The
      subtype-specific evaluation revealed that the tumour-infiltrating lymphocytic
      infiltrate is a positive outcome predictor in ECC and GBAC but not in ICC.
      CONCLUSION: Our findings characterise the immune response in
      cholangiocarcinogenesis and identify inflammatory cell types that influence the
      outcome of BTC patients. Further, we show that BTC subtypes show relevant
      differences with respect to density, quality of inflammation, and impact on
      patient survival.

PMID- 24136147
TI  - Nutlin-3 preferentially sensitises wild-type p53-expressing cancer cells to DR5
      selective TRAIL over rhTRAIL.
AB  - BACKGROUND: Tumour cell-selective activation of apoptosis by recombinant human
      TNF-related apoptosis-inducing ligand (rhTRAIL) is enhanced through co-activation
      of p53 by chemotherapeutic drugs. The novel anticancer agent nutlin-3 provides a
      promising alternative for p53 activation by disrupting the interaction between
      p53 and its negative feedback regulator MDM2. METHODS: We examined whether nutlin
      3 enhances apoptosis induction by rhTRAIL and the DR5-selective TRAIL variant
      D269H/E195R in wild-type p53-expressing ovarian, colon and lung cancer cell lines
      and in an ex vivo model of human ovarian cancer. RESULTS: Nutlin-3 enhanced p53,
      p21, MDM2 and DR5 surface expression. Although nutlin-3 did not induce apoptosis,
      it preferentially enhanced D269H/E195R-induced apoptosis over rhTRAIL.
      Combination treatment potentiated the cleavage of caspases 8, 9, 3 and PARP. P53
      and MDM2 siRNA experiments showed that this enhanced apoptotic effect was
      mediated by wild-type p53. Indeed, nutlin-3 did not enhance rhTRAIL-induced
      apoptosis in OVCAR-3 cells harbouring mutant p53. Addition of the
      chemotherapeutic drug cisplatin to the combination further increased p53 and DR5
      levels and rhTRAIL- and D269H/E195R-induced apoptosis. As a proof of concept, we
      show that the combination of D269H/E195R, nutlin-3 and cisplatin induced massive
      apoptosis in ex vivo tissue slices of primary human ovarian cancers. CONCLUSION:
      Nutlin-3 is a potent enhancer of D269H/E195R-induced apoptosis in wild-type p53
      expressing cancer cells. Addition of DNA-damaging agents such as cisplatin
      further enhances DR5-mediated apoptosis.

PMID- 24136148
TI  - Type- and age-specific distribution of human papillomavirus in women attending
      cervical cancer screening in Finland.
AB  - BACKGROUND: Large-scale data on type-specific HPV prevalences and disease burden
      are needed to monitor the impact of HPV vaccination and to plan for HPV-based
      cervical screening. METHODS: 33 043 women (aged 25-65) were screened for HPV by a
      Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women
      (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type
      specific prevalence of HPV infection and its correlation to findings in cytology
      triage and histology as well as Population Attributable Fractions for a referral
      to colposcopy and findings in histology were calculated. RESULTS: Among HC2
      positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more
      severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained
      the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group
      2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping.
      The proportion of samples positive for HPV by the HC2, but negative in HPV
      genotyping increased with age and decreased with increasing cytological
      abnormality. The most frequent types were HPV 16 (0.9% of screened women and
      12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52
      (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased
      with increasing CIN grade and attributed 78.3% (95% CI 53.4-89.9) of the CIN 3+
      lesions, while HPV 16 attributed 55.8% (40.0-67.5) of them. CONCLUSION: The type
      specific prevalence of HPV were slightly lower than the average in international
      meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than
      cytology triage at the threshold of LSIL+. The high proportion of women that were
      HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be
      useful also for validation of results in HPV screening. The large-scale HPV
      genotyping data were found to be directly useful for planning further preventive
      efforts for cervical cancer.

PMID- 24136149
TI  - Deregulation of DNA-dependent protein kinase catalytic subunit contributes to
      human hepatocarcinogenesis development and has a putative prognostic value.
AB  - BACKGROUND: The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs)
      favours or inhibits carcinogenesis, depending on the cancer type. Its role in
      human hepatocellular carcinoma (HCC) is unknown. METHODS: DNA-dependent protein
      kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock
      transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or
      immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation,
      apoptosis, microvessel density and genomic instability were also determined. Heat
      shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of
      both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was
      evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate
      Cox model were used to study the impact on clinical outcome. RESULTS: Total and
      phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs
      positively correlated with HCC proliferation, genomic instability and microvessel
      density, and negatively with apoptosis and patient's survival. Proliferation
      decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines.
      Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC.
      Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through
      the activation of the MAPK/JNK/AP-1 axis. CONCLUSION: DNA-dependent protein
      kinase catalytic subunit transduces HSF1 effects in HCC cells, and might
      represent a novel target and prognostic factor in human HCC.

PMID- 24136150
TI  - DICER1 hotspot mutations in non-epithelial gonadal tumours.
AB  - BACKGROUND: Non-epithelial gonadal tumours largely comprise sex cord-stromal
      tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in
      DICER1, a microRNA maturation pathway gene, have been identified in these
      tumours. We conducted a study that aimed to confirm, refine and extend the
      previous observations. METHODS: We used Sanger sequencing to sequence the RNase
      IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19
      males, as well as 43 extra-gonadal GCTs from 26 females and 17 males. RESULTS: We
      identified heterozygous non-synonymous mutations in the RNase IIIb domain of
      DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28
      SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8
      miscellaneous tumours. The 14 mutations affected only five residues: E1705,
      D1709, E1788, D1810 and E1813. In all five patients where matched and
      constitutional DNA was available, the mutations were only somatic. There were no
      mutations found in the RNase IIIa domain. CONCLUSION: More than half (8/15) of
      Sertoli-Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb
      domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs
      may aid in classification and provide new approaches to therapy.

PMID- 24136151
TI  - A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for
      Hodgkin lymphoma incorporating biomarkers of response and toxicity.
AB  - BACKGROUND: Myelotoxicity during initial cycles of chemotherapy for Hodgkin
      lymphoma is associated with better outcome, supporting the concept of
      individualised dosing based on pharmacodynamic end points to optimise results.
      This study was performed to identify the maximum tolerated dose (MTD) of
      doxorubicin within cycles 1-3 ABVD (doxorubicin, bleomycin, vinblastine,
      dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and
      epithelial toxicity (Cytokeratin 18, CK18) were also measured. METHODS: Dose
      escalation of doxorubicin in cycles 1-3 ABVD supported by pegfilgrastim was
      performed on a six-patient cohort basis (35, 45 and 55 mg m(-2)) with doxorubicin
      reduced to 25 mg m(-2) or omitted in cycles 4-6 to maintain cumulative exposure
      of 103-130% standard ABVD. BVD was given at standard doses throughout. Six
      additional subjects were recruited at the MTD. RESULTS: Twenty-four subjects were
      recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis,
      palmar-plantar erythema and neutropenic infection were observed at 55 mg m(-2),
      so 45 mg m(-2) was declared the MTD. In patients who subsequently experienced DLT
      at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD.
      CONCLUSION: Escalated ABVD incorporating doxorubicin at 45 mg m(-2) in cycles 1-3
      can be delivered safely with pegfilgrastim support. Circulating cell death
      biomarkers may assist in the development of future individualised dosing
      strategies.

PMID- 24136152
TI  - Activity, severity and impact of respiratory disease in primary antibody
      deficiency syndromes.
AB  - PURPOSE: Some patients with primary antibody deficiency (PAD) syndromes develop
      bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico
      pathophysiological relationships exist between exacerbation frequency, lung
      function, health-status, infection and inflammation. It is not known whether such
      relationships are present in PAD. It is also not known how local and systemic
      inflammation in PAD compares with that in immunocompetent (non-PAD)
      bronchiectasis patients. METHOD: We assessed symptoms, exacerbation frequency,
      health-status, lung function, CT, airway and systemic inflammation and infection
      in 33 PAD patients and 20 immunocompetent controls with bronchiectasis. RESULTS:
      Despite less severe airflow obstruction, PAD patients had similar health-status
      impairment and greater airway (sputum log10 IL-6 2.71 vs. 1.81 pg/ml, p = 0.001)
      and greater systemic inflammation than immunocompetent bronchiectasis controls
      (serum log10 CRP 0.77 vs. 0.36 mg/l, p = 0.001). In PAD, cross-sectional markers
      of disease severity (CT and lung function) did not relate to inflammatory markers
      of disease activity, however there was a relationship between FEV1 decline rate
      and systemic inflammation (IL-6; r = 0.42, p = 0.036) and the magnitude of the
      systemic inflammatory response was related to that in the airway. Correlation
      between generic SF36 and respiratory SGRQ questionnaires (r = -0.79, p < 0.001)
      suggests that much health-status impairment in PAD relates to respiratory
      involvement. Health-status was associated with dyspnoea (rho = 0.77, p < 0.001),
      respiratory infection frequency (rho = 0.48, p = 0.016), lung function (FEV1: r =
      -0.60, p = 0.001) and rate of lung function decline (r = 0.41, p = 0.047).
      CONCLUSION: The major findings of this analysis are that in patients with PAD,
      cross-sectional markers of disease severity such as lung function and CT extent
      of disease do not reflect disease activity as assessed by airway and systemic
      inflammation. In addition, there is a relationship between the rate of
      progression of lung disease and the severity of the systemic inflammatory
      response which itself is related to that in the airway. Much of the quality of
      life impact in PAD relates to respiratory involvement, specifically the severity
      of airflow obstruction, respiratory exacerbation frequency and dyspnoea. Finally,
      patients with PAD had greater airway and systemic inflammation than a control
      population with non-PAD bronchiectasis which may suggest a dysregulated airway
      immune response.

PMID- 24136153
TI  - Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism
      after total hip arthroplasty: a randomised phase IIb dose confirmation study
      (ONYX-3).
AB  - This double-blind, double-dummy, randomised, phase IIb study (NCT00902928)
      evaluated different dosing regimens of darexaban compared with enoxaparin
      (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg
      bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip
      arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded
      to treatment allocation. Darexaban administration started 6-10 hours (h) post
      surgery. Enoxaparin 40 mg qd administration started 12 +/- 2 h before surgery.
      Treatment continued for 35 days. Bilateral venography was performed on Day 10 +/-
      2. The primary efficacy outcome was total VTEs (composite of proximal/distal deep
      vein thrombosis, pulmonary embolism) or death, at Day 12. Total VTE rates were
      similar across all groups. There was no apparent difference in efficacy between
      once- and twice-daily darexaban (odds ratio [OR] 1.00; 95% confidence interval
      [CI] 0.71-1.42; p=0.988), or total daily dose (30 mg/day vs 60 mg/day; OR 0.81;
      95% CI 0.57-1.15; p=0.244). There was no significant difference in major and/or
      clinically relevant non-major bleeding between darexaban qd or bid, or between
      total daily doses of 30 mg or 60 mg, and also for any dosing regimen of darexaban
      vs enoxaparin. Darexaban was well tolerated, without signs of liver toxicity. In
      conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg
      or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data
      suggest no significant differences between a once- or twice-daily dosing regimen.

PMID- 24136154
TI  - Room temperature switching of a neutral molecular iron(II) complex.
AB  - Abrupt room temperature switching (T(c) = 295 K with a 5 K hysteresis) was
      achieved in a neutral Fe(II) complex based on a 2-(1H-pyrazol-1-yl)-6-(1H
      tetrazol-5-yl)pyridine ligand. Structural characterization and spin crossover
      study (via SQUID magnetometry, photoexcitation and X-ray absorption spectroscopy)
      in the solid state are described.

PMID- 24136155
TI  - Comparative analysis of late functional outcome following preoperative radiation
      therapy or chemoradiotherapy and surgery or surgery alone in rectal cancer.
AB  - PURPOSE: This study evaluates the anorectal and genitourinary function of
      patients treated by preoperative short-term radiotherapy (RT) or
      chemoradiotherapy (CRT) followed by surgery and surgery alone for rectal cancer.
      METHODS: For this study, a total of 613 patients, who were identified from a
      prospective rectal cancer database, underwent anterior resection of the rectum
      between October 2001 and December 2007. Standardized questionnaires were used to
      determine fecal incontinence, urinary, and sexual function. Relevant clinical
      variables were evaluated using univariate and multivariate analyses. Independent
      predictors of functional outcome were identified by a binary logistic regression
      analysis. RESULTS: The data of 263 (43 %) patients were available for analysis.
      On multivariate analysis, neoadjuvant RT (P < 0.01) and low anterior resection
      (LAR) (P = 0.049) were associated with fecal incontinence. In univariate
      analysis, fecal incontinence was linked to preoperative neoadjuvant treatment (RT
      and/or CRT vs. LAR) (P < 0.01). The hazard ratio for developing fecal
      incontinence was 3.3 (1.6-6.8) for patients who received RT. One hundred twenty
      five patients (51.2 %) experienced urinary incontinence following surgery, the
      majority of whom were female (P < 0.01). On univariate analysis, male sexual
      function was associated with age (P < 0.01), ASA class (P = 0.01) and LAR (P =
      0.01). CONCLUSION: Multimodal therapy of low rectal cancer increases the
      incidence of fecal incontinence and negatively affects sexual function. The
      potential benefits of RT or CRT need to be balanced against the risk of increased
      bowel dysfunction when determining the appropriate treatment for individual
      patients with rectal cancer.

PMID- 24136156
TI  - Use of factor scores for predicting body weight from linear body measurements in
      three South African indigenous chicken breeds.
AB  - Body weight and weight of body parts are of economic importance. It is difficult
      to directly predict body weight from highly correlated morphological traits
      through multiple regression. Factor analysis was carried out to examine the
      relationship between body weight and five linear body measurements (body length,
      body girth, wing length, shank thickness, and shank length) in South African
      Venda (VN), Naked neck (NN), and Potchefstroom koekoek (PK) indigenous chicken
      breeds, with a view to identify those factors that define body conformation.
      Multiple regression was subsequently performed to predict body weight, using
      orthogonal traits derived from the factor analysis. Measurements were obtained
      from 210 chickens, 22 weeks of age, 70 chickens per breed. High correlations were
      obtained between body weight and all body measurements except for wing length in
      PK. Two factors extracted after varimax rotation explained 91, 95, and 83% of
      total variation in VN, NN, and PK, respectively. Factor 1 explained 73, 90, and
      64% in VN, NN, and PK, respectively, and was loaded on all body measurements
      except for wing length in VN and PK. In a multiple regression, these two factors
      accounted for 72% variation in body weight in VN, while only factor 1 accounted
      for 83 and 74% variation in body weight in NN and PK, respectively. The two
      factors could be used to define body size and conformation of these breeds.
      Factor 1 could predict body weight in all three breeds. Body measurements can be
      better selected jointly to improve body weight in these breeds.

PMID- 24136157
TI  - Polymorphisms in the MTRN1A gene and their effects on the productive and
      reproductive traits in buffaloes.
AB  - The main environmental factor that affects the regulation of reproductive
      seasonality is photoperiod through its effects on melatonin secretion. The
      melatonin receptor MTRN1A appears to be involved in regulating the reproductive
      seasonality and milk production in the period. The aim of this study was to
      identify polymorphisms in the MTRN1A gene and their possible associations with
      milk, fat and protein productions, fat and protein percentages, age at first
      calving, and first calving interval in buffaloes. Three genotypes (CC, CT, and
      TT) were identified by PCR-RFLP, and there was a significant association with
      protein percentage (P < 0.0001). Further studies are necessary to better
      understand the influence of melatonin gene and their receptors in the productive
      functions of buffaloes.

PMID- 24136158
TI  - Well-being of newly diagnosed women with breast cancer: which factors matter
      more?
AB  - BACKGROUND: The assessment of health-related quality of life (HRQL) in newly
      diagnosed breast cancer patients is necessary to address predictive factors in
      supportive clinical practice. PURPOSE: The objectives of this study are to
      evaluate self-reported HRQL within 1 year after breast cancer diagnosis and to
      determine important factors associated with self-reported impaired HRQL. METHODS:
      A cross-sectional study was performed in newly diagnosed breast cancer patients.
      The statistical analysis included descriptive statistics and stepwise logistic
      regression modeling. RESULTS: The survey response rate was 67 % (n = 338). Almost
      50 % of the studied population was identified as experiencing anxiety. The
      impaired HRQL domains were emotional functioning and global health status.
      Severely expressed symptoms included insomnia, fatigue, and financial
      difficulties. Poor financial situation, comorbidities, unemployment, and lack of
      psychological counseling were identified as important predictive factors (p <
      0.001). CONCLUSIONS: Psychosocial, but not clinical, factors were the prevalent
      predictive factors in impaired HRQL. Early identification of women that are at
      risk of poorer HRQL and interventions of psychosocial support following breast
      cancer diagnosis are recommended.

PMID- 24136159
TI  - Comparative multidisciplinary prediction of survival in patients with advanced
      cancer.
AB  - PURPOSE: The expected survival of patients with metastatic cancer can
      significantly impact decisions regarding treatment, care setting, and future
      planning. We evaluated the prognostication ability of a multidisciplinary team
      (MDT) experienced in providing supportive care and palliative radiotherapy.
      METHODS: After clinical assessment of consecutive patients, survival predictions
      were independently made by each MDT member. Patient demographics, factors
      influencing predictions, and dates of death were collected. Clinical predictions
      of survival (CPS) were considered correct if within 30 days of actual survival
      (AS). Summary statistics and Kaplan-Meier estimates of overall survival were
      obtained. Correlations between actual and CPS were calculated using Spearman's
      correlation coefficient. Multivariate logistic regression analysis identified
      factors associated with prognostication accuracy. RESULTS: A total of 395
      predictions (06/2010-07/2012) were made by eight disciplines. Average age was 68
      years, 68.3 % of patients were male, and 48.4 % had lung cancer. Median AS was 87
      days (95 % CI 66-102 days). Survival was over-estimated 72.4 % (286/395) of the
      time with r = 0.54 (p < 0.0001) for all predictions across all disciplines. In
      addition, 30.3 % (36/119) of radiation therapist (RTT) predictions were correct
      compared to 30.1 % (22/73) of nurses', 28.7 % (43/150) of physicians', and 15.1 %
      (8/53) of allied health (AH) providers. There were no differences in accuracy by
      discipline except for the RTT versus AH groups (p = 0.04). Factors most
      frequently cited as influencing correct predictions were Karnofsky performance
      status (KPS), extent of disease, and histology. KPS was the only significant
      variable on multivariate analysis (p <= 0.04). CONCLUSION: MDT members providing
      collaborative care for advanced cancer patients utilize similar factors in
      predicting survival with comparable accuracy.

PMID- 24136160
TI  - International pediatric liver cancer pathological classification: current trend.
AB  - This review describes the pathological classification of pediatric liver cancer
      types and subtypes proposed at the recent international symposium (March 2011,
      Los Angeles, USA) and meetings involving pathologists serving as central
      reviewers for the Children's Oncology Group, Societe Internationale d'Oncologie
      Pediatrique, Gesellschaft fur Padiatrische Onkologie und Hamatologie, or Japanese
      Study Group for Pediatric Liver Tumors, and pediatric oncologists/surgeons
      specializing in liver cancers, as well as immunohistochemical panels,
      recommendations for submission, sampling and evaluation of diagnostic specimens.
      The pathological classification is intended to be standardized and clinically
      meaningful, thus improving future patient management and prognosis. The most
      common pediatric liver cancer is hepatoblastoma (HBL). HBL has two types, the
      wholly epithelial type and the mixed epithelial and mesenchymal (MEM) type. The
      wholly epithelial type was subdivided into well-differentiated fetal (pure fetal
      with low mitotic activity), crowded fetal (mitotically active), embryonal,
      epithelial mixed, small cell undifferentiated, and cholangioblastic. A
      macrotrabecular pattern and a pleomorphic epithelial pattern were recognized as
      supplemental features of epithelial components. The MEM type was subdivided into
      MEM without teratoid features and MEM with teratoid features. Other liver cancers
      in children were divided into hepatocellular carcinoma (classic hepatocellular
      carcinoma and fibrolamellar carcinoma) and hepatocellular malignant tumor not
      otherwise specified. This classification is basically applied to pretreatment
      specimens; the evaluation of post-chemotherapy specimens will be the subject of
      further studies. 

PMID- 24136161
TI  - ArCH(OMe)2--a Pt(IV)-catalyst originator for diverse annulation catalysis.
AB  - We discover an important property of a small molecule ArCH(OMe)2 which transforms
      catalytically inactive Pt(II)Br2 procatalyst in situ to an powerful catalyst
      Pt(IV)-species for diverse annulation reaction. The powerful catalytic system
      enables selective activation of C2-H/N-H and C2-H/C4-H of acetoacetanilide and
      C=O/C=C of substituted butyne-1,2-dione for C-C/C-N, C-C/C-C and C-O/C-O bond
      forming inter- and intramolecular annulation towards direct syntheses of
      functionalised 2-pyridones, cyclohexenones and 3(2H)-furanones respectively. In
      contrast to the common ligand, herein highly labile C-OMe bond of ArCH(OMe)2 is
      expected to react with PtBr2 towards generation of the high-valent active
      catalyst. Unlike catalyst promoter or initiator, the reaction does not occur with
      PtBr2 in the absence of ArCH(OMe)2. In situ generation of Pt(IV)-species and -OMe
      fragment of ArCH(OMe)2 were confirmed from the UV-vis characteristic peaks about
      260 nm and trapping of -OMe group respectively. These observations provide new
      prospects and perspectives in catalysis for innovative catalyst design.

PMID- 24136162
TI  - Nonmetric cranial trait variation and population history of medieval East Slavic
      tribes.
AB  - The population history of the East Slavs is complicated. There are still many
      unanswered questions relating to the origins and formation of the East Slavic
      gene pool. The aims of the current study were as follows: (1) to assess the
      degree of biological affinity in medieval East Slavic tribes and to test the
      hypothesis that East Slavic peoples have a common origin; (2) to show their
      genetic connections to the autochthonous populations of the northern part of
      Eastern Europe (Baltic and Finno-Ugric tribes); and (3) to identify a genetic
      continuity between the bearers of Chernyakhov culture and medieval Eastern Slavs.
      In this study, nonmetric cranial trait data for medieval East Slavic tribes and
      comparative samples from unrelated groups were examined. Analyzes of phenotypic
      differentiation were based on Nei's standard genetic distance and hierarchical
      GST statistics. The results obtained suggest that the genetic affinity of the
      East Slavic tribes is due not only to inter-tribal gene flow, but is, more
      importantly, a result of their common population history. Evidence of gene flow
      from the Baltic and Finno-Ugric groups was showed in the gene pool of Eastern
      Slavs, as was genetic continuity between medieval East Slavic tribes and the
      populations of the preceding Chernyakhov culture. These findings support a
      "generalizing" hypothesis of East Slavic origin, in which a Slavic community was
      formed in some particular ancestral area, and subsequently spread throughout
      Eastern Europe.

PMID- 24136163
TI  - Gestational diabetes: update of screening strategy and diagnostic criteria.
AB  - PURPOSE OF REVIEW: To review recently published studies examining new data on
      screening strategies and diagnostic criteria for gestational diabetes (GDM).
      RECENT FINDINGS: Professional organizations continue to have differing
      recommendations concerning the best screening strategy for GDM. An independent
      expert panel appointed by the National Institutes of Health has recently
      recommended to continue with the two-step approach for screening. Recent evidence
      shows that the glucose challenge test seems acceptable to screen for GDM but that
      an Hba1c measurement is not a good alternative. The International Association of
      Diabetes and Pregnancy Study Groups (IADPSG) screening strategy remains
      controversial with studies showing a high inconsistency in associations with
      adverse pregnancy outcome and cost-effectiveness analyses show conflicting
      results. To reduce the number of oral glucose tolerance tests needed, clinical
      prediction models may be implemented. SUMMARY: It is now generally accepted that,
      especially in high-risk women, overt diabetes should be excluded at first
      prenatal visit. However, internationally the debate on the best screening
      strategy for GDM continues. In most populations the implementation of the IADPSG
      screening strategy will lead to an important increase in the prevalence of GDM
      and associated costs and workload. Risk stratification in IADPSG-positive women
      may reduce over-treatment. Using clinical prediction models may be a more cost
      effective alternative.

PMID- 24136164
TI  - Three-dimensional reconstruction of intact human integrin alphaIIbbeta3: new
      implications for activation-dependent ligand binding.
AB  - Integrin alphaIIbbeta3 plays a central role in hemostasis and thrombosis. We
      provide the first 3-dimensional reconstruction of intact purified alphaIIbbeta3
      in a nanodisc lipid bilayer. Unlike previous models, it shows that the ligand
      binding head domain is on top, pointing away from the membrane. Moreover, unlike
      the crystal structure of the recombinant ectodomain, the lower legs are not
      parallel, straight, and adjacent. Rather, the alphaIIb lower leg is bent between
      the calf-1 and calf-2 domains and the beta3 Integrin-Epidermal Growth Factor (I
      EGF) 2 to 4 domains are freely coiled rather than in a cleft between the beta3
      headpiece and the alphaIIb lower leg. Our data indicate an important role for the
      region that links the distal calf-2 and beta-tail domains to their respective
      transmembrane (TM) domains in transmitting the conformational changes in the TM
      domains associated with inside-out activation. 

PMID- 24136166
TI  - The EBV oncogene LMP1 protects lymphoma cells from cell death through the
      collagen-mediated activation of DDR1.
AB  - The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma are
      surrounded by a tumor microenvironment that is composed of a variety of cell
      types, as well as noncellular components such as collagen. Although HRS cells
      harbor oncogenic Epstein-Barr virus (EBV) in approximately 50% of cases, it is
      not known if the tumor microenvironment contributes to EBV-driven
      lymphomagenesis. We show that expression of the EBV-encoded latent membrane
      protein-1 (LMP1) in primary human germinal center B cells, the presumed
      progenitors of HRS cells, upregulates discoidin domain receptor 1 (DDR1), a
      receptor tyrosine kinase activated by collagen. We also show that HRS cells
      intimately associated with collagen frequently overexpress DDR1 and that short
      term exposure to collagen is sufficient to activate DDR1 in Hodgkin lymphoma
      derived cell lines. The ectopic expression of DDR1 significantly increased the
      survival of collagen-treated DG75 Burkitt lymphoma cells, following etoposide
      treatment. Conversely, knockdown of DDR1 significantly decreased the survival of
      collagen-treated L428 Hodgkin lymphoma cells in the absence of specific apoptotic
      stimulus, suggesting that DDR1 also influences baseline survival. Our results
      identify a hitherto unknown function for collagen in protecting Hodgkin lymphoma
      cells from apoptosis and suggest an important contribution of the tumor
      microenvironment in promoting the oncogenic effects of EBV. 

PMID- 24136167
TI  - MicroRNA-155 controls RB phosphorylation in normal and malignant B lymphocytes
      via the noncanonical TGF-beta1/SMAD5 signaling module.
AB  - MicroRNA-155 (miR-155) plays pleiotropic roles in the biology of normal and
      malignant B lymphocytes, including the modulation of the transforming growth
      factor beta (TGF-beta) pathway via the targeting of SMAD5. However, the extent of
      the miR-155-mediated disruption of the TGF-beta1/SMAD5 axis remains to be
      elucidated. To address this issue, we used the miR-155 knockout (KO) mouse and
      diffuse large B-cell lymphoma (DLBCL) cell lines ectopically expressing miR-155.
      In the DLBCL models, expression of miR-155 blocked TGF-beta1-mediated activation
      of the retinoblastoma protein (RB), decreasing the abundance of the inhibitory
      pRB-E2F1 complex and limiting G0/G1 arrest. Genetic knockdown of SMAD5, p15, or
      p21 recapitulated these effects, establishing a circuitry whereby the targeting
      of SMAD5 by miR-155 blunts the TGF-beta1-induced transcription of p15 and p21,
      thus sustaining RB phosphorylation and inactivity. Next, we demonstrated that
      SMAD5 levels are elevated in mature B lymphocytes from the miR-155 KO mice, which
      display a heightened sensitivity to TGF-beta1 characterized by suppression of RB
      phosphorylation and more pronounced G0/G1 cell cycle arrest. Our findings suggest
      that a miR-155-mediated perturbation of the RB/E2F axis may play a role in DLBCL
      pathogenesis, and contribute to the reduced number of germinal center B cells and
      impaired T cell-dependent antibody response found in the miR-155 KO mice. 

PMID- 24136168
TI  - Renal subcapsular hemorrhage complicating ureterolithotripsy: an unknown
      complication of a known day-to-day procedure.
AB  - OBJECTIVE: To report the incidence, risk factors, and treatments of renal
      subcapsular hemorrhage (RSH) complicating ureteroscopic lithotripsy (URSL).
      PATIENTS AND METHODS: Data from 1,918 URSLs performed between January 2004 and
      March 2012 were retrospectively analyzed. Patients' data included age, sex,
      relevant medical history, stone side, size, and degree of hydronephrosis.
      RESULTS: All 8 patients were identified as having an RSH after URSL. There were 2
      males and 6 females with a mean age of 45.6 years (range 30-62 years). The
      patients' relevant medical histories (renal calculi extracorporeal shock wave
      lithotripsy, renal operation and hypertension) were statistically different
      between those who did and did not develop an RSH. Acute onset of flank pain is
      the most common symptom. Three patients with infective and large hemorrhage were
      managed by percutaneous nephrostomy in 1 and percutaneous subcapsular drainage in
      2. Five patients with small and uninfected hemorrhage were managed
      conservatively. CONCLUSIONS: The rate of development of RSH complicating URSL is
      very low. RSH complicating URSL can occur in patients with underlying renal
      abnormalities. RSH is rarely associated with abrupt hemodynamic instability and
      usually not lethal. Treatment is selected based on the patient's hemodynamic
      state, infection, renal function, and the feasibility of treatment modality.

PMID- 24136165
TI  - The genetic basis of myelodysplasia and its clinical relevance.
AB  - Myelodysplasia is a diagnostic feature of myelodysplastic syndromes (MDSs) but is
      also found in other myeloid neoplasms. Its molecular basis has been recently
      elucidated by means of massive parallel sequencing studies. About 90% of MDS
      patients carry >=1 oncogenic mutations, and two thirds of them are found in
      individuals with a normal karyotype. Driver mutant genes include those of RNA
      splicing (SF3B1, SRSF2, U2AF1, and ZRSR2), DNA methylation (TET2, DNMT3A, and
      IDH1/2), chromatin modification (ASXL1 and EZH2), transcription regulation
      (RUNX1), DNA repair (TP53), signal transduction (CBL, NRAS, and KRAS), and
      cohesin complex (STAG2). Only 4 to 6 genes are consistently mutated in >=10% MDS
      patients, whereas a long tail of ~50 genes are mutated less frequently. At
      presentation, most patients typically have 2 or 3 driver oncogenic mutations and
      hundreds of background mutations. MDS driver genes are also frequently mutated in
      other myeloid neoplasms. Reliable genotype/phenotype relationships include the
      association of the SF3B1 mutation with refractory anemia with ring sideroblasts,
      TET2/SRSF2 comutation with chronic myelomonocytic leukemia, and activating CSF3R
      mutation with chronic neutrophilic leukemia. Although both founding and subclonal
      driver mutations have been shown to have prognostic significance, prospective
      clinical trials that include the molecular characterization of the patient's
      genome are now needed. 

PMID- 24136169
TI  - Vismodegib for periocular and orbital basal cell carcinoma.
AB  - IMPORTANCE: Basal cell carcinoma (BCC) represents 90% of malignant eyelid tumors
      and is locally invasive and destructive, if left untreated. OBJECTIVE: To assess
      the feasibility of using vismodegib for periocular and orbital BCC based on its
      efficacy and tolerability. DESIGN, SETTING, AND PARTICIPANTS: In this prospective
      observational case series, consecutive patients with periocular or orbital BCC
      who met criteria for treatment with vismodegib were recruited prospectively
      during an 8-month period from February through September 2012 from 2 academic
      hospitals. Seven patients received oral vismodegib, 150 mg daily, until maximum
      clinical response was achieved, the tumor progressed, or the patient could no
      longer tolerate adverse effects. Clinical response and adverse effects related to
      treatment were recorded. The primary endpoint was reduction in lesion size,
      measured as percentage change in the externally visible dimension. EXPOSURE: Oral
      vismodegib. RESULTS: All 7 patients had locally advanced, biopsy-proven,
      infiltrative BCC that was not amenable to surgical resection or radiation. No
      patients had metastatic disease at presentation. The mean patient age was 71
      years (range, 43-100 years), and 4 patients (57%) had secondary orbital
      involvement. The mean lesion size was 3.4 cm (range, 1.0-6.0 cm), and all 7 cases
      (100%) represented recurrent tumors excised previously with controlled margins by
      frozen section or Mohs micrographic surgery. The mean treatment duration was 11
      weeks (range, 4-16 weeks), and the mean duration of follow-up was 7.3 months
      (range, 5-10 months). Two patients (29%) demonstrated complete clinical
      regression, 2 (29%) demonstrated greater than 80% partial clinical regression, 2
      (29%) demonstrated less than 35% partial clinical regression, and 1 (14%)
      progressed. Adverse reactions occurred in 6 patients (86%) and included alopecia
      (29%), dysgeusia (29%), muscle cramps (29%), and anorexia (14%). Two patients
      (29%) developed new squamous cell carcinomas (well-differentiated,
      keratoacanthoma type) at uninvolved sites including the eyebrow and forearm.
      CONCLUSIONS AND RELEVANCE: Vismodegib seems to be well-tolerated and effective
      for treating periocular and orbital BCC in about half of all cases. Patients
      receiving treatment should be monitored for new squamous cell carcinomas at
      uninvolved sites.

PMID- 24136170
TI  - Pathological motivations for exercise and eating disorder specific health-related
      quality of life.
AB  - OBJECTIVE: To examine associations among pathological motivations for exercise
      with eating disorder (ED) specific health-related quality of life (HRQOL).
      METHOD: Survey data assessing ED severity (i.e., Eating Disorder Diagnostic
      Survey), ED specific HRQOL (i.e., Eating Disorders Quality of Life Instrument),
      and pathological motivations for exercise (i.e., Exercise Dependence Scale) were
      collected from female students (N = 387) at seven universities throughout the
      United States. Regression analyses were conducted to examine the associations
      among exercise dependence, ED-specific HRQOL and ED severity, and the interaction
      of exercise dependence and ED severity on HRQOL scores. RESULTS: The overall
      model examining the impact of ED severity and exercise dependence (independent
      variables) on HRQOL (dependent variable) was significant and explained 16.1% of
      the variance in HRQOL scores. Additionally, the main effects for ED severity and
      exercise dependence and the interaction among ED severity and exercise dependence
      were significant, suggesting that the combined effects of ED severity and
      exercise dependence significantly impacts HRQOL. DISCUSSION: Our results suggest
      that pathological motivations for exercise may exacerbate ED's detrimental impact
      on HRQOL. Our results offer one possible insight into why exercise may be
      associated with deleterious effects on ED HRQOL. Future research is needed to
      elucidate the relationship among psychological aspects of exercise, ED, and
      HRQOL.

PMID- 24136171
TI  - Role of PKC-beta in chemical allergen-induced CD86 expression and IL-8 release in
      THP-1 cells.
AB  - We previously demonstrated an age-related decrease in receptor for activated C
      kinase (RACK-1) expression and functional deficit in Langerhans cells'
      responsiveness. This defect specifically involves the translocation of protein
      kinase C (PKC)-beta. The purpose of this study was to investigate the role of
      RACK-1 and PKC-beta in chemical allergen-induced CD86 expression and IL-8 release
      in the human promyelocytic cell line THP-1 and primary human dendritic cells
      (DC). Dinitrochlorobenzene, p-phenylenediamine and diethyl maleate were used as
      contact allergens. The selective cell-permeable inhibitor of PKC-beta and the
      broad PKC inhibitor GF109203X completely prevented chemical allergen- or
      lipopolysaccharide (LPS)-induced CD86 expression and significantly modulated IL-8
      release (50 % reduction). The selective cell-permeable inhibitor of PKC-epsilon
      (also known to bind to RACK-1) failed to modulate allergen- or LPS-induced CD86
      expression or allergen-induced IL-8 release, while modulating LPS-induced IL-8
      release. The use of a RACK-1 pseudosubstrate, which directly activates PKC-beta,
      resulted in dose-related increase in CD86 expression and IL-8 release. Similar
      results were obtained with human DC, confirming the relevance of results obtained
      in THP-1 cells. Overall, our findings demonstrate the role of PKC-beta and RACK-1
      in allergen-induced CD86 expression and IL-8 production, supporting a central
      role of PKC-beta in the initiation of chemical allergen-induced DC activation.

PMID- 24136174
TI  - Multidrug therapy and evolution of antibiotic resistance: when order matters.

PMID- 24136172
TI  - A farnesoic acid O-methyltransferase (FAMeT) from Exopalaemon carinicauda is
      responsive to Vibrio anguillarum and WSSV challenge.
AB  - Methyl farnesoate (MF), an analogue of the insect juvenile hormone III, is
      believed to play important roles in the regulation of the growth and reproductive
      development in crustaceans. Farnesoic acid O-methyltransferase (FAMeT) is the key
      enzyme in the juvenile hormone biosynthetic pathway, involved in the conversion
      of farnesoic acid (FA) to MF in the final step of MF synthesis. In this study, a
      FAMeT cDNA (named EcFAMeT) was cloned from the hemocytes of ridgetail white prawn
      Exopalaemon carinicauda by rapid amplification of cDNA ends (RACE) methods. The
      full-length cDNA of EcFAMeT was 1,620 bp, including contains a 5'-untranslated
      region (UTR) of 75 bp, 3'-UTR of 714 bp with a poly (A) tail, an open reading
      frame (ORF) of 831 bp, encoding a 276-amino-acid polypeptide with the predicted
      molecular weight of 31.57 kDa and estimated isoelectric point of 4.67. BLAST
      analysis revealed that amino acids of EcFAMeT shared high identity (75-90 %) with
      that of other crustaceans. Two conserved signatures domains of Methyltransf-FA
      superfamily were also identified in EcFAMeT. Real time quantitative RT-PCR
      analysis indicated that EcFAMeT could be detected in all the tested tissues and
      strongly expressed in hepatopancreas and ovary of E. carinicauda. After Vibrio
      anguillarum and WSSV challenge, EcFAMeT transcripts both in hemocytes and
      hepatopancreas increased significantly in the first 3 h, respectively. The
      results indicated that EcFAMeT might be associated with the immune defenses to V.
      anguillarum and WSSV in E. carinicauda.

PMID- 24136176
TI  - Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas
      aeruginosa to beta-lactams.
AB  - AmpC beta-lactamase confers resistance to beta-lactam antibiotics in many Gram
      negative bacteria. Inducible expression of AmpC requires an N
      acetylglucosaminidase termed NagZ. Here we describe the synthesis and
      characterization of hydroxyazepane inhibitors of NagZ. We find that these
      inhibitors enhance the susceptibility of clinically relevant Pseudomonas
      aeruginosa to beta-lactams. 

PMID- 24136177
TI  - Motility efficiency and spatiotemporal synchronization in non-metastatic vs.
      metastatic breast cancer cells.
AB  - Metastatic breast cancer cells move not only more rapidly and persistently than
      their non-metastatic variants but in doing so use the mechanical work of the
      cytoskeleton more efficiently. The efficiency of the cell motions is defined for
      entire cells (rather than parts of the cell membrane) and is related to the work
      expended in forming membrane protrusions and retractions. This work, in turn, is
      estimated by integrating the protruded and retracted areas along the entire cell
      perimeter and is standardized with respect to the net translocation of the cell.
      A combination of cross-correlation, Granger causality, and morphodynamic
      profiling analyses is then used to relate the efficiency to the cell membrane
      dynamics. In metastatic cells, the protrusions and retractions are highly
      "synchronized" both in space and in time and these cells move efficiently. In
      contrast, protrusions and retractions formed by non-metastatic cells are not
      "synchronized" corresponding to low motility efficiencies. Our work provides a
      link between the kinematics of cell motions and their energetics. It also
      suggests that spatiotemporal synchronization might be one of the hallmarks of
      invasiveness of cancerous cells. 

PMID- 24136178
TI  - Plasmon-induced photonic and energy-transfer enhancement of solar water splitting
      by a hematite nanorod array.
AB  - Plasmonic metal nanostructures offer a promising route to improve the solar
      energy conversion efficiency of semiconductors. Here we show that incorporation
      of a hematite nanorod array into a plasmonic gold nanohole array pattern
      significantly improves the photoelectrochemical water splitting performance,
      leading to an approximately tenfold increase in the photocurrent at a bias of
      0.23 V versus Ag|AgCl under simulated solar radiation. Plasmon-induced resonant
      energy transfer is responsible for enhancement at the energies below the band
      edge, whereas above the absorption band edge of hematite, the surface plasmon
      polariton launches a guided wave mode inside the nanorods, with the nanorods
      acting as miniature optic fibres, enhancing the light absorption. In addition,
      the intense local plasmonic field can suppress the charge recombination in the
      hematite nanorod photoanode in a photoelectrochemical cell. Our results may
      provide a general approach to overcome the low optical absorption and spectral
      utilization of thin semiconductor nanostructures, while further reducing charge
      recombination losses. 

PMID- 24136179
TI  - Retraction note to: CT and MR findings in a neuroforaminal extraskeletal Ewing
      sarcoma mimicking benign nerve sheath tumor. Ir J Med Sci (2012) 181:123-5.

PMID- 24136181
TI  - Coarsening dynamics of three-dimensional levitated foams: From wet to dry.
AB  - We study diamagnetically levitated foams with widely different liquid fractions.
      Due to the levitation, drainage is effectively suppressed and the dynamics is
      driven by the coarsening of the foam bubbles. For dry foams, the bubble size is
      found to increases as the square root of foam age, as expected from a generalized
      von Neumann law. At higher liquid content the behavior changes to that of Ostwald
      ripening where the bubbles grow with the 1/3 power of the age. Using Diffusing
      Wave Spectroscopy we study the local dynamics in the different regimes and find
      diffusive behavior for dry foams and kinetic behavior for wet foams. 

PMID- 24136182
TI  - A secondary working memory challenge preserves primary place strategies despite
      overtraining.
AB  - Learning by repetition engages distinct cognitive strategies whose contributions
      are adjusted with experience. Early in learning, performance relies upon
      flexible, attentive strategies. With extended practice, inflexible, automatic
      strategies emerge. This transition is thought fundamental to habit formation and
      applies to human and animal cognition. In the context of spatial navigation,
      place strategies are flexible, typically employed early in training, and rely on
      the spatial arrangement of landmarks to locate a goal. Response strategies are
      inflexible, become dominant after overtraining, and utilize fixed motor
      sequences. Although these strategies can operate independently, they have also
      been shown to interact. However, since previous work has focused on single-choice
      learning, if and how these strategies interact across sequential choices remains
      unclear. To test strategy interactions across sequential choices, we utilized
      various two-choice spatial navigation tasks administered on the Opposing Ts maze,
      an apparatus for rodents that permits experimental control over strategy
      recruitment. We found that when a second choice required spatial working memory,
      the transition to response navigation on the first choice was blocked. Control
      experiments specified this effect to the cognitive aspects of the secondary task.
      In addition, response navigation, once established on a single choice, was not
      reversed by subsequent introduction of a secondary choice reliant on spatial
      working memory. These results demonstrate that performance strategies interact
      across choices, highlighting the sensitivity of strategy use to the cognitive
      demands of subsequent actions, an influence from which overtrained rigid actions
      may be protected. 

PMID- 24136183
TI  - Sparing of spatial mental imagery in patients with hippocampal lesions.
AB  - In four experiments, we explored the capacity for spatial mental imagery in
      patients with hippocampal lesions, using tasks that minimized the role of
      learning and memory. On all four tasks, patients with hippocampal lesions
      performed as well as controls. Nonetheless, in separate tests, the patients were
      impaired at remembering the materials that had been used to assess mental
      imagery. The findings suggest that the hippocampus is not needed for constructing
      many forms of spatial imagery but is needed for the formation of long-term
      memory. In future studies of the neural organization of spatial mental imagery,
      it will be important to separate the contribution of spatial processing from the
      contribution of learning and memory. 

PMID- 24136184
TI  - The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian
      men with prostate-specific antigen levels of 4-10 ng/mL.
AB  - PURPOSE: To investigate the role of the Prostate Health Index (phi) in prostate
      cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level
      of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population.
      METHODS: This was a retrospective study of archived serum samples from patients
      enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10
      ng/mL, a negative digital rectal examination, and received their first prostatic
      biopsy between April 2008 and April 2013, were recruited. The serum sample
      collected before biopsy was retrieved for the measurement of various PSA
      derivatives and the phi value was calculated for each patient. The performance of
      these parameters in predicting the prostatic biopsy results was assessed.
      RESULTS: Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed
      with PCa, were recruited for this study. Statistically significant differences
      between PCa patients and non-PCa patients were found for total PSA, PSA density,
      [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio
      (%p2PSA), and phi. The areas under the curve of the receiver operating
      characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were
      0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best
      predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of
      the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients.
      CONCLUSIONS: Use of the phi could improve the accuracy of PCa detection in
      patients with an elevated PSA level and thus avoid unnecessary prostatic
      biopsies.

PMID- 24136185
TI  - Prostate cancer risk after anti-androgen treatment for priapism.
AB  - BACKGROUND: Patients with recurrent ischemic priapism have historically been
      treated with anti-androgen therapy due to the limited available evidence for more
      targeted therapies to treat the underlying pathophysiologic mechanisms of this
      condition. We report a case in which anti-androgen therapy caused significant
      adverse side effects and likely masked this patient's elevated prostate-specific
      antigen (PSA) levels, which adversely impacted the timely diagnosis and treatment
      of his prostate cancer. CASE REPORT: A 69-year-old man treated with anti
      androgens for priapism initially developed unwanted anti-androgenic side effects
      such as gynecomastia, erectile dysfunction, and decreased libido. After
      decreasing his anti-androgen dosage and starting a specified regimen of
      phosphodiesterase type 5 inhibitor therapy, his serum PSA levels were found to be
      elevated. He was subsequently diagnosed with adenocarcinoma of the prostate and
      underwent a radical prostatectomy with the pathologic finding of high-grade,
      locally progressive disease. CONCLUSION: Anti-androgen therapy carries
      significant complication risks, including the potential to alter the diagnosis
      and treatment of prostate cancer. Clinicians administering this therapy for
      priapism management should be aware of these possible risks.

PMID- 24136186
TI  - The prevalence of lower urinary tract symptoms in a Chinese population, and the
      correlation with uroflowmetry and disease perception.
AB  - OBJECTIVES: To evaluate the prevalence of lower urinary tract symptoms (LUTS) in
      a population of Chinese men, and its correlation with uroflowmetry and disease
      perception. MATERIALS AND METHODS: Male volunteers above 40-year old were
      recruited in the community. Assessment with International Prostatic Symptom Score
      (IPSS), uroflowmetry, and a quiz on prostatic disease knowledge with 12 true
      false-type questions were performed. Correlation of IPSS with uroflowmetry
      results and prostatic disease knowledge was analyzed. RESULTS: A total of 319 men
      were recruited for the study, with a mean age of 62 +/- 8 years. About 69.3 % of
      them had moderate-to-severe symptoms on IPSS. A statistically significant
      correlation was found between IPSS and Q max (r = -0.260, p < 0.001), IPSS and
      quality of life (r = -0.172, p = 0.002), and IPSS and post-void residuals (r =
      0.223, p < 0.001). About 53.0 % of subjects had less than 4 correct answers for
      the 12 true-false questions. Negative correlation was noted between the number of
      correct answers and IPSS (r = -0.185, p = 0001). In other words, for the better
      knowledge on prostatic diseases, the lower IPSS was found. CONCLUSIONS: In a
      cohort of community-dwelling Chinese men, a significant portion of the population
      had moderate-to-severe LUTS. While uroflowmetry parameters were found to
      correlate with IPSS, the degree of knowledge on prostatic diseases also shared a
      statistically significant correlation with IPSS. This has an implication on the
      role of urological health education in the future.

PMID- 24136187
TI  - Actual medical management of lower urinary tract symptoms related to benign
      prostatic hyperplasia: temporal trends of prescription and hospitalization rates
      over 5 years in a large population of Italian men.
AB  - PURPOSE: The purpose of the study is to estimate the trends in drug prescriptions
      and the hospitalization rates for lower urinary tract symptoms/benign prostatic
      hyperplasia (LUTS/BPH) in real-life clinical practice, using information deriving
      from administrative databases of the Italian health care system. METHODS:
      Prescription data on approximately 1,500,000 men over 40 were examined, and
      prescribed boxes of alpha-blockers (ABs) and/or 5 alpha reductase inhibitors
      (5ARI) were calculated for 5 consecutive years, from 2004 to 2008. Annual use
      prevalence and incidence rates for each drug class and for the combination
      therapy (CT) were calculated according to age for the entire study period.
      Hospitalization rates for reasons related to LUTS/BPH were also evaluated for the
      same time period. RESULTS: The overall distribution of drugs for LUTS/BPH, in
      terms of number of boxes prescribed, increased by 43 %. This increase was
      accounted for by both classes of drugs although it was greater for 5ARI than for
      AB (+49 vs +41 %). The prevalence of CT showed a substantial increase to almost
      25 % in patients aged >=75. Hospitalization rate for BPH/LUTS-related reasons
      decreased during the study period (8 and 3 % per year for non-surgical and
      surgical reasons, respectively). CONCLUSIONS: The prevalence of the use of drugs
      prescribed for LUTS/BPH has steadily increased. An increase in terms of
      prescribed boxes was observed for both classes of drugs, even though the increase
      was greater for 5ARIs. The reduction in the hospitalization rates needs
      additional researches.

PMID- 24136188
TI  - Utilization of causal reasoning of hepatic gene expression in rats to identify
      molecular pathways of idiosyncratic drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) represents a leading cause of acute liver
      failure. Although DILI can be discovered in preclinical animal toxicology studies
      and/or early clinical trials, some human DILI reactions, termed idiosyncratic
      DILI (IDILI), are less predictable, occur in a small number of individuals, and
      do not follow a clear dose-response relationship. The emergence of IDILI poses a
      critical health challenge for patients and a financial challenge for the
      pharmaceutical industry. Understanding the cellular and molecular mechanisms
      underlying IDILI is key to the development of models that can assess potential
      IDILI risk. This study used Reverse Causal Reasoning (RCR), a method to assess
      activation of molecular signaling pathways, on gene expression data from rats
      treated with IDILI or pharmacologic/chemical comparators (NON-DILI) at the
      maximum tolerated dose to identify mechanistic pathways underlying IDILI.
      Detailed molecular networks involved in mitochondrial injury, inflammation, and
      endoplasmic reticulum (ER) stress were found in response to IDILI drugs but not
      negative controls (NON-DILI). In vitro assays assessing mitochondrial or ER
      function confirmed the effect of IDILI compounds on these systems. Together our
      work suggests that using gene expression data can aid in understanding mechanisms
      underlying IDILI and can guide in vitro screening for IDILI. Specifically, RCR
      should be considered for compounds that do not show evidence of DILI in
      preclinical animal studies positive for mitochondrial dysfunction and ER stress
      assays, especially when the therapeutic index toward projected human maximum drug
      plasma concentration is low. 

PMID- 24136189
TI  - High risk of embryo-fetal toxicity: placental transfer of T-2 toxin and its major
      metabolite HT-2 toxin in BeWo cells.
AB  - Though T-2 toxin is the most harmful mycotoxin to the fetuses, it remains unclear
      whether T-2 toxin and its major metabolite, HT-2 toxin, could pass the placenta
      into the fetus and which kind of placental transport is involved in the passage.
      To illustrate their placenta transfer mechanism, the uptake and efflux of T-2 and
      HT-2 toxins across apical membranes of placenta with BeWo cells as a model were
      studied at different temperatures, pHs, and in the presence of transporter
      inhibitors with a developed liquid chromatography-tandem mass spectrometry to
      determine the amount of toxins in both fetal and maternal sites. Higher
      unidirectional transport of T-2 toxin was observed in the apical-to-basolateral
      direction than basolateral-to-apical one, whereas HT-2 toxin exhibited similar
      transport rate from the 2 directions. The main ATP-binding cassette transporters
      had no effect on the efflux of 2 toxins. Initial uptake of T-2 toxin was sodium
      dependent and saturable, and the apical uptake was temperature dependent and
      enhanced under acidic condition. The apical uptake of T-2 toxin was inhibited by
      metabolic inhibitors and the organic anion and organic cation transporter
      inhibitors. These results suggested that an active transport mechanism was
      responsible for the uptake of T-2 toxin, whereas passive diffusion was the
      principal mechanism for HT-2 toxin transport in the placenta. Taken together,
      these data characterized the placental transfer of T-2 and HT-2 toxins. The
      present study offered new ways of reducing the risks of T-2 and HT-2 toxins to
      both mother and fetuses. 

PMID- 24136190
TI  - Nucleotide specificity of DNA binding of the aryl hydrocarbon receptor:ARNT
      complex is unaffected by ligand structure.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD, dioxin) and a wide variety of structurally diverse ligands through
      its ability to translocate into the nucleus and bind to a specific DNA
      recognition site (the dioxin-responsive element [DRE]) adjacent to responsive
      genes. Although the sequence of the DRE is well defined, several reports
      suggested that the nucleotide specificity of AhR DNA binding may vary depending
      on the structure of its bound ligand. Given the potential toxicological
      significance of this hypothesis, an unbiased DNA-selection-and-PCR-amplification
      approach was utilized to directly determine whether binding and activation of the
      AhR by structurally diverse agonists alter its nucleotide specificity of DNA
      binding. Guinea pig hepatic cytosolic AhR activated in vitro by equipotent
      concentrations of TCDD, 3-methylcholanthrene, beta-naphthoflavone, indirubin, L
      kynurenine, or YH439 was incubated with a pool of DNA oligonucleotides containing
      a 15-base pair variable region consisting of all possible nucleotides. The AhR
      bound oligonucleotides isolated by immunoprecipitation were PCR amplified and
      used in subsequent rounds of selection. Sequence analysis of a total of 196
      isolated oligonucleotides revealed that each ligand-activated AhR:ARNT complex
      only bound to DRE-containing DNA oligonucleotides; no non-DRE-containing DNA
      oligonucleotides were identified. These results demonstrate that the binding and
      activation of the AhR by structurally diverse agonists do not appear to alter its
      nucleotide specificity of DNA binding and suggest that stimulation of gene
      expression mediated by direct DNA binding of ligand-activated AhR:ARNT complexes
      is DRE dependent. 

PMID- 24136191
TI  - Multidimensional in vivo hazard assessment using zebrafish.
AB  - There are tens of thousands of man-made chemicals in the environment; the
      inherent safety of most of these chemicals is not known. Relevant biological
      platforms and new computational tools are needed to prioritize testing of
      chemicals with limited human health hazard information. We describe an
      experimental design for high-throughput characterization of multidimensional in
      vivo effects with the power to evaluate trends relating to commonly cited
      chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2
      compounds using the embryonic zebrafish and found that 487 induced significant
      adverse biological responses. The utilization of 18 simultaneously measured
      endpoints means that the entire system serves as a robust biological sensor for
      chemical hazard. The experimental design enabled us to describe global patterns
      of variation across tested compounds, evaluate the concordance of the available
      in vitro and in vivo phase 1 data with this study, highlight specific
      mechanisms/value-added/novel biology related to notochord development, and
      demonstrate that the developmental zebrafish detects adverse responses that would
      be missed by less comprehensive testing strategies. 

PMID- 24136192
TI  - Plutonium release from Fukushima Daiichi fosters the need for more detailed
      investigations.
AB  - The contamination of Japan after the Fukushima accident has been investigated
      mainly for volatile fission products, but only sparsely for actinides such as
      plutonium. Only small releases of actinides were estimated in Fukushima.
      Plutonium is still omnipresent in the environment from previous atmospheric
      nuclear weapons tests. We investigated soil and plants sampled at different hot
      spots in Japan, searching for reactor-borne plutonium using its isotopic ratio
      240Pu/239Pu. By using accelerator mass spectrometry, we clearly demonstrated the
      release of Pu from the Fukushima Daiichi power plant: While most samples
      contained only the radionuclide signature of fallout plutonium, there is at least
      one vegetation sample whose isotope ratio (0.381 +/- 0.046) evidences that the Pu
      originates from a nuclear reactor (239+240Pu activity concentration 0.49 Bq/kg).
      Plutonium content and isotope ratios differ considerably even for very close
      sampling locations, e.g. the soil and the plants growing on it. This strong
      localization indicates a particulate Pu release, which is of high radiological
      risk if incorporated.

PMID- 24136193
TI  - Oxygenation advisor recommends appropriate positive end expiratory pressure and
      FIO2 settings: retrospective validation study.
AB  - A decision support, rule-based oxygenation advisor that provides guidance for
      setting positive end expiratory pressure (PEEP) and fractional inhaled oxygen
      concentration (FIO2) for patients with respiratory failure is described. The
      target oxygenation goal is to achieve and maintain pulse oximeter oxygen
      saturation (SpO2) >= 88 and <= 95%, as posited by the Acute Respiratory Distress
      Syndrome Network, by recommending appropriate combinations of PEEP and FIO2. For
      patient safety, the oxygenation advisor monitors mean arterial blood pressure
      (MAP) to ensure it is >= 65 mmHg for hemodynamic stability and inspiratory
      plateau pressure (Pplt) so it is <= 30 cm H2O for lung protection. The purpose of
      this validation study was to compare attending physicians' recommendations to
      those recommendations of the oxygenation advisor for setting PEEP and FIO2.
      Adults with respiratory failure (n = 117) receiving ventilatory support were
      studied. PEEP, FIO2, SpO2, MAP, and Pplt are input variables into the advisor.
      Recommendations to increase, maintain, or decrease PEEP and FIO2 are the
      oxygenation advisor's output variables. Physicians' recommendations for setting
      PEEP and FIO2 were recorded; the oxygenation advisor's recommendations were also
      recorded for comparison. At all times, ventilator settings were based on
      recommendations from attending physicians. PEEP ranged from 2 to 22 cm H2O and
      FIO2 ranged from 0.30 to 0.65. A total of 326 recommendations by the oxygenation
      advisor and attending physicians were made to increase, maintain, or decrease
      PEEP and FIO2. There was a very significant relationship (p < 0.0001) between
      recommendations of the oxygenation advisor and attending physicians for setting
      PEEP and FIO2. The agreement rate for recommendations by the oxygenation advisor
      and attending physicians was 92%. The K statistic, a test of the strength of
      agreement of recommendations between the oxygenation advisor and attending
      physicians, was 0.82 (p < 0.0001), indicating "almost perfect agreement".
      Relationships for recommendations made by the oxygenation advisor and attending
      physicians for setting PEEP and FIO2 were excellent, PEEP: r = 0.98 (p < 0.01),
      r(2) = 0.96; FIO2: r = 0.91 (p < 0.01), r(2) = 0.83, bias and precision values
      were negligible. A novel oxygenation advisor provided continuous and automatic
      recommendations for setting PEEP and FIO2 that were shown to be as good as the
      clinical judgment of experienced attending physicians. For all patients, the
      target oxygenation goal was achieved. Concerning patient safety, the oxygenation
      advisor detected those occasions when MAP and Pplt were in potentially unsafe
      ranges.

PMID- 24136194
TI  - The use of regional cerebral oximetry monitoring during controlled hypotension: a
      case series.
AB  - Regional cerebral oximetry monitoring was used to guide nitroglycerin infusion
      and IV fluid administration during controlled hypotension in order to optimize
      each individual patient's mean arterial pressure in a series of 20 consecutive
      patients who underwent major open urological or abdominal surgery. Although
      controlled hypotension offers a definite benefit in patients undergoing complex
      surgery where blood loss will be elevated or would severely compromise the
      surgical field, it is not without risk as low arterial pressure may compromise
      tissue perfusion and promote ischemia. In this case series, despite an average
      mean arterial pressure decrease of 19.5 % (p < 0.001), cerebral oximetry values
      increased by an average of 22.7 % (p < 0.001) after the nitroglycerin infusion
      had been initiated (220 mcg/min average). Patients received an average of 3.15L
      crystalloid and 437 ml albumin in fluid resuscitation.

PMID- 24136195
TI  - Cytosolic sulfotransferase 1A3 is induced by dopamine and protects neuronal cells
      from dopamine toxicity: role of D1 receptor-N-methyl-D-aspartate receptor
      coupling.
AB  - Dopamine neurotoxicity is associated with several neurodegenerative diseases, and
      neurons utilize several mechanisms, including uptake and metabolism, to protect
      them from injury. Metabolism of dopamine involves three enzymes: monoamine
      oxidase, catechol O-methyltransferase, and sulfotransferase. In primates but not
      lower order animals, a sulfotransferase (SULT1A3) is present that can rapidly
      metabolize dopamine to dopamine sulfate. Here, we show that SULT1A3 and a closely
      related protein SULT1A1 are highly inducible by dopamine. This involves
      activation of the D1 and NMDA receptors. Both ERK1/2 phosphorylation and
      calcineurin activation are required for induction. Pharmacological agents that
      inhibited induction or siRNA targeting SULT1A3 significantly increased the
      susceptibility of cells to dopamine toxicity. Taken together, these results show
      that dopamine can induce its own metabolism and protect neuron-like cells from
      damage, suggesting that SULT1A3 activity may be a risk factor for dopamine
      dependent neurodegenerative diseases. 

PMID- 24136196
TI  - Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive
      function in a mouse model of Alzheimer disease.
AB  - Isoprenoids and prenylated proteins have been implicated in the pathophysiology
      of Alzheimer disease (AD), including amyloid-beta precursor protein metabolism,
      Tau phosphorylation, synaptic plasticity, and neuroinflammation. However, little
      is known about the relative importance of the two protein prenyltransferases,
      farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), in the
      pathogenesis of AD. In this study, we defined the impact of deleting one copy of
      FT or GGT on the development of amyloid-beta (Abeta)-associated neuropathology
      and learning/memory impairments in APPPS1 double transgenic mice, a well
      established model of AD. Heterozygous deletion of FT reduced Abeta deposition and
      neuroinflammation and rescued spatial learning and memory function in APPPS1
      mice. Heterozygous deletion of GGT reduced the levels of Abeta and
      neuroinflammation but had no impact on learning and memory. These results
      document that farnesylation and geranylgeranylation play differential roles in AD
      pathogenesis and suggest that specific inhibition of protein farnesylation could
      be a potential strategy for effectively treating AD. 

PMID- 24136197
TI  - Understanding the role of argininosuccinate lyase transcript variants in the
      clinical and biochemical variability of the urea cycle disorder argininosuccinic
      aciduria.
AB  - Argininosuccinic aciduria (ASA) is an autosomal recessive urea cycle disorder
      caused by deficiency of argininosuccinate lyase (ASL) with a wide clinical
      spectrum from asymptomatic to severe hyperammonemic neonatal onset life
      threatening courses. We investigated the role of ASL transcript variants in the
      clinical and biochemical variability of ASA. Recombinant proteins for ASL wild
      type, mutant p.E189G, and the frequently occurring transcript variants with exon
      2 or 7 deletions were (co-)expressed in human embryonic kidney 293T cells. We
      found that exon 2-deleted ASL forms a stable truncated protein with no relevant
      activity but a dose-dependent dominant negative effect on enzymatic activity
      after co-expression with wild type or mutant ASL, whereas exon 7-deleted ASL is
      unstable but seems to have, nevertheless, a dominant negative effect on mutant
      ASL. These findings were supported by structural modeling predictions for ASL
      heterotetramer/homotetramer formation. Illustrating the physiological relevance,
      the predominant occurrence of exon 7-deleted ASL was found in two patients who
      were both heterozygous for the ASL mutant p.E189G. Our results suggest that ASL
      transcripts can contribute to the highly variable phenotype in ASA patients if
      expressed at high levels. Especially, the exon 2-deleted ASL variant may form a
      heterotetramer with wild type or mutant ASL, causing markedly reduced ASL
      activity. 

PMID- 24136199
TI  - It's all about money: oral contraception alters neural reward processing.
AB  - Mating preferences in phases of the natural menstrual cycle with a low
      probability to conceive have been associated with lower interest in
      characteristics promising genetic benefits but increased search for safety and
      future security. We hypothesized that this effect would also be evident under
      oral contraception and may therefore alter neural processing of monetary rewards
      as a proxy for potential safety. Our aim was to assess the activation of reward
      related brain areas using a monetary incentive task in women with functional MRI
      (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives
      with 12 women with a natural hormonal cycle in their follicular phase during the
      expectation of monetary rewards. Women under hormonal contraception who have
      already shown decreased anterior insula activation upon erotic stimulation in a
      previous study of the same sample now showed enhanced activation during monetary
      reward expectation in the anterior insula/inferior lateral prefrontal cortex
      (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase.
      Our finding supports the notion that the switch in mating preferences related to
      different hormonal states in women is mirrored by a switch in the stimulus
      dependent excitability of reward-related brain regions. Beyond highlighting
      hormonal effects on reward processing, our data underline the importance of
      monitoring hormonal states in fMRI research in women. 

PMID- 24136198
TI  - Point mutation in syntaxin-1A causes abnormal vesicle recycling, behaviors, and
      short term plasticity.
AB  - Syntaxin-1A is a t-SNARE that is involved in vesicle docking and vesicle fusion;
      it is important in presynaptic exocytosis in neurons because it interacts with
      many regulatory proteins. Previously, we found the following: 1) that
      autophosphorylated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an
      important modulator of neural plasticity, interacts with syntaxin-1A to regulate
      exocytosis, and 2) that a syntaxin missense mutation (R151G) attenuated this
      interaction. To determine more precisely the physiological importance of this
      interaction between CaMKII and syntaxin, we generated mice with a knock-in (KI)
      syntaxin-1A (R151G) mutation. Complexin is a molecular clamp involved in
      exocytosis, and in the KI mice, recruitment of complexin to the SNARE complex was
      reduced because of an abnormal CaMKII/syntaxin interaction. Nevertheless, SNARE
      complex formation was not inhibited, and consequently, basal neurotransmission
      was normal. However, the KI mice did exhibit more enhanced presynaptic plasticity
      than wild-type littermates; this enhanced plasticity could be associated with
      synaptic response than did wild-type littermates; this pronounced response
      included several behavioral abnormalities. Notably, the R151G phenotypes were
      generally similar to previously reported CaMKII mutant phenotypes. Additionally,
      synaptic recycling in these KI mice was delayed, and the density of synaptic
      vesicles was reduced. Taken together, our results indicated that this single
      point mutation in syntaxin-1A causes abnormal regulation of neuronal plasticity
      and vesicle recycling and that the affected syntaxin-1A/CaMKII interaction is
      essential for normal brain and synaptic functions in vivo. 

PMID- 24136201
TI  - GPs are reluctant to promote patient choice, health minister says.

PMID- 24136200
TI  - Cytokine-dependent regulation of dendritic cell differentiation in the splenic
      microenvironment.
AB  - The DC-derived chemokine CCL17, a ligand of CCR4, has been shown to promote
      various inflammatory diseases such as atopic dermatitis, atherosclerosis, and
      inflammatory bowel disease. Under steady-state conditions, and even after
      systemic stimulation with LPS, CCL17 is not expressed in resident splenic DCs as
      opposed to CD8alpha-CD11b+ LN DCs, which produce large amounts of CCL17 in
      particular after maturation. Upon systemic NKT cell activation through alpha
      galactosylceramide stimulation however, CCL17 can be upregulated in both CD8alpha
      and CD8alpha+ splenic DC subsets and enhances cross-presentation of exogenous
      antigens. Based on genome-wide expression profiling, we now show that splenic
      CD11b+ DCs are susceptible to IFN-gamma-mediated suppression of CCL17, whereas LN
      CD11b+CCL17+ DCs downregulate the IFN-gammaR and are much less responsive to IFN
      gamma. Under inflammatory conditions, particularly in the absence of IFN-gamma
      signaling in IFN-gammaRKO mice, CCL17 expression is strongly induced in a major
      proportion of splenic DCs by the action of GM-CSF in concert with IL-4. Our
      findings demonstrate that the local cytokine milieu and differential cytokine
      responsiveness of DC subsets regulate lymphoid organ specific immune responses at
      the level of chemokine expression.

PMID- 24136202
TI  - Reversing the new oral anticoagulants with prothrombin complex concentrates
      (PCCs): what is the evidence?
AB  - Newer oral anticoagulants offer several advantages over traditional agents (e.g.
      warfarin), but they are still associated with a bleeding risk and currently there
      is no validated reversal treatment for them. While there is little support for
      the use of fresh frozen plasma, and limited data available on the effects of
      activated recombinant factor VII, preclinical data suggest that prothrombin
      complex concentrates (PCCs) may have potential in this setting. PCCs are
      currently used to successfully reverse warfarin-induced anticoagulation; however,
      clinical evidence for their use with new oral anticoagulants is lacking, with
      most of the available data coming from preclinical animal studies. Furthermore,
      there appears to be variation in the ability of different PCCs to reverse the
      coagulopathy induced by the new anticoagulants, and a lack of correlation between
      the reversal of laboratory test results and the reversal of anticoagulant-induced
      bleeding. Although there have been encouraging results, care must be taken in
      generalising findings from animal models and nonbleeding human subjects to the
      situation in bleeding patients. Ultimately, more evidence supporting
      anticoagulation reversal for new anticoagulants is needed, particularly regarding
      the treatment of bleeding in human patients in a clinical setting. According to
      the current evidence, use of PCCs may be considered a reasonable approach in dire
      clinical situations; however, a consensus has not yet been reached regarding PCC
      use or dosing, due to lack of clinical data.

PMID- 24136203
TI  - Training-induced changes in clotting parameters of athletic horses.
AB  - The purpose of this study was to investigate the effects of training on
      prothrombin time, activated partial thromboplastin time, and fibrinogen (Fb)
      concentrations in horses to assess potential adaptive response to training.
      Fifteen clinically healthy horses were enrolled in the present study and equally
      divided into three groups. Group A completed an intense training program, group B
      participated in a light training program, and group C included sedentary horses.
      After 5 weeks, group B was subjected to the same training program completed by
      group A and renamed group B1. Blood samples were collected by jugular
      venipuncture from each animal at rest and analyzed within 2 h after sampling. A
      two-way ANOVA for repeated measures showed a significant effect of training (p <
      0.05) on Fb concentrations in group B1 alone during the first week after changing
      the training program. Our findings demonstrated that Fb is a parameter
      susceptible to training. Fb plasma levels increase with a more intense training
      program. However, Fb plasma levels decreased after the first week and returned to
      basel levels, suggesting that the horses had adapted to the new training program.

PMID- 24136204
TI  - Positive effects of porcine IL-2 and IL-4 on virus-specific immune responses
      induced by the porcine reproductive and respiratory syndrome virus (PRRSV) ORF5
      DNA vaccine in swine.
AB  - The purpose of this study was to investigate the effects of porcine interleukin
      (IL)-2 and IL-4 genes on enhancing the immunogenicity of a porcine reproductive
      and respiratory syndrome virus ORF5 DNA vaccine in piglets. Eukaryotic expression
      plasmids pcDNA-ORF5, pcDNA-IL-2, and pcDNA-IL-4 were constructed and then
      expressed in Marc-145 cells. The effects of these genes were detected using an
      indirect immunofluorescent assay and reverse transcription polymerase chain
      reaction (RT-PCR). Characteristic fluorescence was observed at different times
      after pcDNA- ORF5 was expressed in the Marc-145 cells, and PCR products
      corresponding to ORF5, IL-2, and IL-4 genes were detected at 48 h. Based on these
      data, healthy piglets were injected intramuscularly with different combinations
      of the purified plasmids: pcDNA-ORF5 alone, pcDNA-ORF5 + pcDNA-IL-2, pcDNA-ORF5 +
      pcDNA-IL-4, and pcDNA-ORF5 + pcDNA- IL-4 + pcDNA-IL-2. The ensuing humoral immune
      responses, percentages of CD4(+) and CD8(+) T lymphocytes, proliferation indices,
      and interferon-g expression were analyzed. Results revealed that the piglets co
      immunized with pcDNA-ORF5 + pcDNA-IL-4 + pcDNA-IL-2 plasmids developed
      significantly higher antibody titers and neutralizing antibody levels, had
      significantly increased levels of specific T lymphocyte proliferation, elevated
      percentages of CD4(+) and CD8(+) T lymphocytes, and significantly higher IFN
      gamma production than the other inoculated pigs (p < 0.05).

PMID- 24136205
TI  - Toxic effects of methylmercury, arsanilic acid and danofloxacin on the
      differentiation of mouse embryonic stem cells into neural cells.
AB  - This study was performed to assess the neurotoxic effects of methylmercury,
      arsanilic acid and danofloxacin by quantification of neural-specific proteins in
      vitro. Quantitation of the protein markers during 14 days of differentiation
      indicated that the mouse ESCs were completely differentiated into neural cells by
      Day 8. The cells were treated with non-cytotoxic concentrations of three
      chemicals during differentiation. Low levels of exposure to methylmercury
      decreased the expression of GABAA-R and Nestin during the differentiating stage,
      and Nestin during the differentiated stage. In contrast, GFAP, Tuj1, and MAP2
      expression was affected only by relatively high doses during both stages.
      Arsanilic acid affected the levels of GABAA-R and GFAP during the differentiated
      stage while the changes of Nestin and Tuj1 were greater during the
      differentiating stage. For the neural markers (except Nestin) expressed during
      both stages, danofloxacin affected protein levels at lower concentrations in the
      differentiated stage than the differentiating stage. Acetylcholinesterase
      activity was inhibited by relatively low concentrations of methylmercury and
      arsanilic acid during the differentiating stage while this activity was inhibited
      only by more than 40 MUM of danofloxacin in the differentiated stage. Our results
      provide useful information about the different toxicities of chemicals and the
      impact on neural development.

PMID- 24136206
TI  - Immunohistochemical evaluation of the goat forestomach during prenatal
      development.
AB  - Here we report the detection and distribution of synaptophysin (SPY), non
      neuronal enolase (NNE), glial fibrillary acidic protein (GFAP), vimentin (VIM),
      neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) expression in the
      goat forestomach during prenatal development. A total of 140 embryos and fetuses
      were examined to evaluate protein expression from the first stage of prenatal
      life until birth. In all cases, SPY immunoreactivity was detected at 53 days
      gestation in the lamina propria-submucosa, tunica muscularis, serosa, and
      myenteric plexuses. Immunoreactivity to NNE was observed at 64 days gestation in
      the same locations as well as the epithelial layer. Glial cells were found at 64
      days as indicated by signals corresponding to GFAP and VIM at 39 days. Positive
      staining for NPY and VIP was observed at 113, 75, and 95 days in the rumen,
      reticulum, and omasum, respectively, in the lamina propria-submucosa, tunica
      muscularis, and myenteric plexuses of each of these gastric compartments. These
      findings indicate possible preparation of the fetal goat forestomach for
      postnatal function. Compared to other ruminant species, neuroendocrine cells,
      glial cells and peptidergic innervations markers were detected earlier compared
      to sheep but at around the same stage as in deer. 

PMID- 24136207
TI  - Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer
      therapy for 16 cases of malignant soft tissue sarcoma.
AB  - Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines)
      were treated with a novel triple therapy that combined photodynamic therapy,
      hyperthermia using indocyanine green with a broadband light source, and local
      chemotherapy after surgical tumor resection. This triple therapy was called
      photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin
      was insufficient. In one feline case, PHCT was performed without surgical
      resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated
      three to 21 times. No severe side effects, including severe skin burns, necrosis,
      or skin suture rupture, were observed in any of the animals. No disease
      recurrence was observed in seven out of 10 (70.0%) dogs and three out of six
      (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These
      results suggest that PHCT decreases the risk of STS recurrence. PHCT should
      therefore be considered an adjuvant therapy for treating companion animals with
      STS in veterinary medicine.

PMID- 24136208
TI  - Equine hyperimmune serum protects mice against Clostridium difficile spore
      challenge.
AB  - Clostridium (C.) difficile is a common cause of nosocomial diarrhea in horses.
      Vancomycin and metronidazole have been used as standard treatments but are only
      moderately effective, which highlights the need for a novel alternative therapy.
      In the current study, we prepared antiserum of equine origin against both C.
      difficile toxins A and B as well as whole-cell bacteria. The toxin-neutralizing
      activities of the antibodies were evaluated in vitro and the prophylactic effects
      of in vivo passive immunotherapy were demonstrated using a conventional mouse
      model. The data demonstrated that immunized horses generated antibodies against
      both toxins A and B that possessed toxin-neutralizing activity. Additionally,
      mice treated with the antiserum lost less weight without any sign of illness and
      regained weight back to a normal range more rapidly compared to the control group
      when challenged orally with 10(7) C. difficile spores 1 day after serum
      injection. These results indicate that intravenous delivery of hyperimmune serum
      can protect animals from C. difficile challenge in a dose-dependent manner.
      Hence, immunotherapy may be a promising prophylactic strategy for preventing C.
      difficile infection in horses. 

PMID- 24136209
TI  - Development and clinical evaluation of a rapid diagnostic kit for feline leukemia
      virus infection.
AB  - Feline leukemia virus (FeLV) causes a range of neoplastic and degenerative
      diseases in cats. To obtain a more sensitive and convenient diagnosis of the
      disease, we prepared monoclonal antibodies specific for the FeLV p27 to develop a
      rapid diagnostic test with enhanced sensitivity and specificity. Among these
      antibodies, we identified two clones (hybridomas 8F8B5 and 8G7D1) that
      specifically bound to FeLV and were very suitable for a diagnostic kit. The
      affinity constants for 8F8B5 and 8G7D1 were 0.35 * 108 and 0.86 * 108,
      respectively. To investigate the diagnostic abilities of the rapid kit using
      these antibodies, we performed several clinical studies. Assessment of analytical
      sensitivity revealed that the detection threshold of the rapid diagnostic test
      was 2 ng/mL for recombinant p27 and 12.5 * 104 IU/mL for FeLV. When evaluating
      252 cat sera samples, the kit was found to have a kappa value of 0.88 compared to
      polymerase chain reaction (PCR), indicating a significant correlation between
      data from the rapid diagnostic test and PCR. Sensitivity and specificity of the
      kit were 95.2% (20/21) and 98.5% (257/261), respectively. Our results
      demonstrated that the rapid diagnostic test would be a suitable diagnostic tool
      for the rapid detection of FeLV infection in cats.

PMID- 24136210
TI  - Computed tomographic evaluation of cervical vertebral canal and spinal cord
      morphometry in normal dogs.
AB  - The height, width, and cross-sectional area of the vertebral canal and spinal
      cord along with the area ratio of spinal cord to vertebral canal in the cervical
      vertebra were evaluated in images obtained using computed tomography (CT).
      Measurements were taken at the cranial, middle, and caudal point of each cervical
      vertebra in eight clinically normal small breed dogs (two Shih Tzu, two Miniature
      Schnauzers, and four mixed breed), 10 Beagles, and four German Shepherds. CT
      myelography facilitated the delineation of the epidural space, subarachnoid
      space, and spinal cord except at the caudal portion of the 7th cervical vertebra.
      The spinal cord had a tendency to have a clear ventral border in the middle
      portion of the vertebral canal and lateral borders near both end plates. The
      height, width, and area of the vertebral canal and spinal cord in the cervical
      vertebra were increased as the size of dog increased. However, the ratio of the
      spinal cord area to vertebral canal area in the small dogs was higher than that
      of the larger dogs. Results of the present study could provide basic and
      quantitative information for CT evaluation of pathologic lesions in the cervical
      vertebra and spinal cord.

PMID- 24136211
TI  - Isolation, in vitro propagation, genetic analysis, and immunogenic
      characterization of an Ehrlichia canis strain from southeastern Brazil.
AB  - Amplification of the 16S rRNA gene from a blood sample obtained from a dog in
      southeastern Brazil was used to confirm a naturally acquired Ehrlichia (E.) canis
      infection. Following isolation and culturing of the new bacterial strain called
      Uberlandia, partial sequences of the dsb and p28 genes were obtained. The dsb
      partial sequence of the novel strain was 100% similar to dsb gene sequences of E.
      canis obtained from different geographic areas around the world. Conversely, the
      p28 partial sequence for the E. canis Uberlandia strain differed at several
      nucleotides from other sequences available in GenBank. To confirm the antigenic
      profile of the Uberlandia strain, an indirect immunofluorescence assay against E.
      canis antigens was performed using dog sera collected from two different areas in
      Brazil (Uberlandia and Sao Paulo). The results suggest that both antigens were
      able to identify animals seropositive for E. canis in Brazil since these
      Brazilian strains appear to be highly conserved. 

PMID- 24136212
TI  - Accuracy of sonographic diagnosis of pneumoperitoneum using the enhanced
      peritoneal stripe sign in Beagle dogs.
AB  - The objective of this study was to evaluate the feasibility and accuracy of
      estimating the smallest amount of abdominal free gas detectible in a large
      population of Beagles by ultrasonography. Healthy dogs were randomly divided into
      three groups: group A that received 0.1 mL of air injected into the peritoneal
      cavity, group B that received 0.2 mL of air injected into the peritoneal cavity,
      and group C that received 0.5 mL of intraperitoneal air. Randomly, some dogs in
      each group did not receive air injection for the negative control. All
      ultrasonographic procedures were performed by individuals blinded to group
      assignments and the presence of intraperitoneal air. The minimum volume of
      consistently detectable air with good accuracy and reliability was 0.2 mL.
      Results of the study demonstrated that the enhanced peritoneal stripe sign (EPSS)
      can verify cases of pneumoperitoneum if more than 0.2 mL of intra-abdominal free
      gas is present The EPSS is a reliable and specific ultrasonographic
      characteristic for diagnosing pneumoperitoneum in dogs.

PMID- 24136213
TI  - A novel low-cost method for Mycobacterium avium subsp. paratuberculosis DNA
      extraction from an automated broth culture system for real-time PCR analysis.
AB  - PCR is a highly accurate technique for confirming the presence of Mycobacterium
      avium subsp. paratuberculosis (Map) in broth culture. In this study, a simple,
      efficient, and low-cost method of harvesting DNA from Map cultured in liquid
      medium was developed. The proposed protocol (Universidad Austral de Chile [UACH])
      was evaluated by comparing its performance to that of two traditional techniques
      (a QIAamp DNA Stool Mini Kit and cethyltrimethylammonium bromide [CTAB] method).
      The results were statistically assessed by agreement analysis for which
      differences in the number of cycles to positive (CP) were compared by Student's t
      test for paired samples and regression analysis. Twelve out of 104 fecal pools
      cultured were positive. The final PCR results for 11 samples analyzed with the
      QIAamp and UACH methods or ones examined with the QIAamp and CTAB methods were in
      agreement. Complete (100%) agreement was observed between data from the CTAB and
      UACH methods. CP values for the UACH and CTAB techniques were not significantly
      different, while the UACH method yielded significantly lower CP values compared
      to the QIAamp kit. The proposed extraction method combines reliability and
      efficiency with simplicity and lower cost. 

PMID- 24136214
TI  - Prostaglandin F receptor expression in intrauterine tissues of pregnant rats.
AB  - In this investigation, we studied the expression and localization of rat
      prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10,
      15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis,
      real-time PCR, and immunohistochemistry. A high level of immunoreactivity was
      observed on gestational Days 20, 21, and 21.5 with the most significant signals
      found on Day 20. FP receptor protein was expressed starting on gestational Day
      15, and a fluctuating unsteady increase was observed until delivery. Uterine FP
      receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The
      transcript level increased significantly on Day 20 and peaked on Day 21.5 just
      before labor (p < 0.05). There was a positive correlation between FP receptor
      mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum
      estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an
      increase FP receptor expression in rat uterus with advancing gestation, a marked
      elevation of expression at term, and a concominant decrease during the postpartum
      period. These findings indicate a role for uterine FP receptors in the mediation
      of uterine contractility at term.

PMID- 24136215
TI  - Protective effects of silymarin on fumonisin B1-induced hepatotoxicity in mice.
AB  - The present study was conducted to investigate the effect of silymarin on
      experimental liver toxication induced by Fumonisin B11 (FB1) in BALB/c mice. The
      mice were divided into six groups (n = 15). Group 1 served as the control. Group
      2 was the silymarin control (100 mg/kg by gavage). Groups 3 and 4 were treated
      with FB1 (Group 3, 1.5 mg/kg FB1, intraperitoneally; and Group 4, 4.5 mg/kg FB1).
      Group 5 received FB1 (1.5 mg/kg) and silymarin (100 mg/kg), and Group 6 was given
      a higher dose of FB1 (4.5 mg/kg FB1) with silymarin (100 mg/kg). Silymarin
      treatment significantly decreased (p < 0.0001) the apoptotic rate. FB1
      administration significantly increased (p < 0.0001) proliferating cell nuclear
      antigen and Ki-67 expression. Furthermore, FB1 elevated the levels of caspase-8
      and tumor necrosis factor-alpha mediators while silymarin significantly reduced
      (p < 0.0001) the expression of these factors. Vascular endothelial growth factor
      (VEGF) and fibroblast growth factor-2 (FGF-2) expressions were significantly
      elevated in Group 4 (p < 0.0001). Silymarin administration alleviated increased
      VEGF and FGF-2 expression levels (p < 0.0001). In conclusion, silymarin
      ameliorated toxic liver damage caused by FB1 in BALB/c mice.

PMID- 24136216
TI  - Regulation of matrix metalloproteinase-9 protein expression by 1alpha, 25-(OH)2D3
      during osteoclast differentiation.
AB  - To investigate 1alpha,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9)
      protein expression during osteoclast formation and differentiation, receptor
      activator of nuclear factor kB ligand (RANKL) and macrophage colony-stimulating
      factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells
      into osteoclasts. The cells were incubated with different concentrations of
      1alpha,25-(OH)2D3 during culturing, and cell proliferation was measured using the
      methylthiazol tetrazolium method. Osteoclast formation was confirmed using
      tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar
      resorption. MMP-9 protein expression levels were measured with Western blotting.
      We showed that 1alpha,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by
      RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their
      nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein
      expression in a concentration-dependent manner. These findings indicate that
      1alpha,25-(OH)2D3 administered at a physiological relevant concentration promoted
      osteoclast formation and could regulate osteoclast bone metabolism by increasing
      MMP-9 protein expression during osteoclast differentiation.

PMID- 24136217
TI  - Cell proliferation and neuroblast differentiation in the dentate gyrus of high
      fat diet-fed mice are increased after rosiglitazone treatment.
AB  - In this study, we determined how rosiglitazone (RSG) differentially affected
      hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD;
      60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after
      initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a
      day to both groups of mice. We measured cell proliferation and neuroblast
      differentiation in the subgranular zone of the dentate gyrus using Ki67 and
      doublecortin (DCX), respectively, as markers. In addition, we monitored the
      effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF)
      in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67
      and DCX-positive cells as well as hippocampal levels of DCX and BDNF were
      significantly decreased in the RSG-treated group compared to the vehicle-treated
      animals. In contrast, the numbers of Ki67- and DCX-positive cells along with
      hippocampal levels of DCX and BDNF in the HFD fed mice were significantly
      increased in the RSG-treated mice compared to the vehicle-treated group. Our data
      demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal
      role in cell proliferation and neuroblast differentiation in the hippocampal
      dentate gyrus.

PMID- 24136218
TI  - Esophageal motility disorder achalasia.
AB  - PURPOSE OF REVIEW: Although not a common disease, the last several years have had
      exciting breakthroughs in better defining the pathophysiology of achalasia,
      classifying the disease with high-resolution manometry and potentially exciting
      new treatments. RECENT FINDINGS: The introduction of high-resolution manometry
      with detailed assessment of lower esophageal sphincter function and peristalsis
      has made it possible to classify achalasia into three subtypes. This becomes
      clinically important as patients with type II achalasia do best with both
      pneumatic dilation and surgical myotomy, whereas type III achalasia may respond
      better to surgery. The first multicenter randomized controlled trial published by
      the European Achalasia Trial group reported similar excellent outcomes over a 2
      year follow-up with both pneumatic dilation and laparoscopic myotomy in a study
      involving nearly 200 achalasia patients. Although longer follow-up is required,
      this supports the continued use of pneumatic dilation for treating achalasia.
      Finally, the novel endoscopic technique of peroral endoscopic myotomy is a
      promising new treatment option for achalasia, but it requires increased
      experiences and careful evaluation before widespread application. SUMMARY: These
      are exciting times in the diagnosis and treatment of achalasia, which will
      definitely improve patient treatment outcomes. However, we still await
      breakthroughs in the basic science arena to identify the actual cause of
      achalasia.

PMID- 24136219
TI  - Alcohol consumption and recurrence of non-B or non-C hepatocellular carcinoma
      after hepatectomy: a propensity score analysis.
AB  - BACKGROUND: The aim of this study was to identify factors related to the
      recurrence of non-B or non-C (NBNC) hepatocellular carcinoma (HCC). STUDY DESIGN:
      Between April 2000 and March 2012, out of 621 consecutive HCC patients at our
      institution, 543 who underwent initial hepatectomy and had no extrahepatic
      metastases were enrolled in the study. Multivariate analysis were performed to
      identify risk factors for poor disease-free survival (DFS). RESULTS: The 5-year
      DFS rate of NBNC (34 %) was better than that of hepatitis virus B (30 %, P =
      0.011) and hepatitis virus C (21 %, P < 0.0001), significantly. Multivariate
      analysis revealed NBNC [hazard ratio (HR), 0.5; 95 % CI, 0.4-0.8; P < 0.0001)] to
      be an independent factor for DFS rate. We constructed a propensity score matching
      model with the 543 patients, and the 5-year DFS rates with and without severe
      alcohol liver disease (ALD) were 31.6 and 47.5 %, respectively (P = 0.013). In
      the 163 NBNC patients, severe ALD, mild ALD, and no ALD were seen in 35, 56, and
      72 patients, respectively. Multivariate analysis revealed a vascular invasion
      into the hepatic vein (HR, 3.3; 95 % CI, 1.7-6.3; P < 0.0001) and severe ALD (HR,
      2.0; 95 % CI, 1.1-3.6; P = 0.020) to be independent risk factors for poor DFS. By
      propensity score matching between mild and severe ALD, the 5-year DFS rates with
      severe and mild ALD were 26 and 50 %, respectively (P = 0.035). CONCLUSIONS: The
      prognoses of NBNC patients were better than those of patients with viral
      infections. Among the NBNC patients, preoperative excessive alcohol intake
      decreased DFS rate of HCC occurrence after surgery.

PMID- 24136220
TI  - Effort-related motivational effects of the pro-inflammatory cytokine interleukin
      1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task.
AB  - RATIONALE: Effort-related motivational symptoms such as anergia and fatigue are
      common in patients with depression and other disorders. Research implicates pro
      inflammatory cytokines in depression, and administration of cytokines can induce
      effort-related motivational symptoms in humans. OBJECTIVES: The present
      experiments focused on the effects of the pro-inflammatory cytokine interleukin 1
      beta (IL-1beta) on effort-related choice behavior. METHODS: Rats were tested on a
      concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which
      assesses the tendency of rats to work for a preferred food (high carbohydrate
      pellets) in the presence of a concurrently available but less preferred
      substitute (laboratory chow). RESULTS: IL-1beta (1.0-4.0 MUg/kg IP) shifted
      choice behavior, significantly decreasing lever pressing and increasing intake of
      the freely available chow. The second experiment assessed the ability of the
      adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3
      methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6,7-tetrahydropurin-3
      yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL
      1beta. MSX-3 attenuated the effort-related impairments produced by IL-1beta,
      increasing lever pressing and also decreasing chow intake. In the same dose range
      that shifted effort-related choice behavior, IL-1beta did not alter food intake
      or preference in parallel free-feeding choice studies, indicating that these low
      doses were not generally suppressing appetite or altering preference for the high
      carbohydrate pellets. In addition, IL-1beta did not affect core body temperature.
      CONCLUSIONS: These results indicate that IL-1beta can reduce the tendency to work
      for food, even at low doses that do not produce a general sickness, malaise, or
      loss of appetite. This research has implications for the involvement of cytokines
      in motivational symptoms such as anergia and fatigue.

PMID- 24136221
TI  - Single-cell clones of liver cancer stem cells have the potential of
      differentiating into different types of tumor cells.
AB  - Cancer stem cells (CSCs) are believed to be a promising target for cancer therapy
      because these cells are responsible for tumor development, maintenance and
      chemotherapy resistance. Finding out the critical factors regulating CSC fate is
      the key for target therapy of CSCs. Just as normal stem cells are regulated by
      their microenvironment (niche), CSCs are also regulated by cells in the tumor
      microenvironment. However, whether various tumor microenvironments can induce
      CSCs to differentiate into different cancer cells is not clear. Here, we show
      that single-cell-cloned CSCs, accidentally obtained from a human liver cancer
      microvascular endothelial cells, express classic stem cell markers, genes
      associated with self-renewal and pluripotent factors and possess colony-forming
      ability in vitro and the ability of serial transplantation in vivo. The single
      cell-cloned CSCs treated with the different tumor cell/tissue-derived conditioned
      culture medium, which is a mimic of carcinoma microenvironment, could
      differentiate into corresponding tumor cells and express specific markers of the
      respective type of tumor cells at the gene, protein and cell levels,
      respectively. Interestingly, this multilineage differentiation potential of
      single-cell-cloned liver CSCs sharply declined after the specific knockdown of
      octamer-binding transcription factor 4 (Oct4) alone, even though they were under
      the same induction conditions (carcinoma microenvironments). These data support
      the hypothesis that single-cell-cloned liver CSCs have the potential of
      differentiating into different types of tumor cells, and the tumor
      microenvironment does play a crucial role in deciding differentiation directions.
      Simultaneously, Oct4 in CSCs is indispensable in this process. These factors are
      promising targets for liver CSC-specific therapy. 

PMID- 24136222
TI  - Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by
      assembling a hexokinase II-Src complex on the mitochondrial surface.
AB  - The biological functions of myotonic dystrophy protein kinase (DMPK), a
      serine/threonine kinase whose gene mutations cause myotonic dystrophy type 1
      (DM1), remain poorly understood. Several DMPK isoforms exist, and the long ones
      (DMPK-A/B/C/D) are associated with the mitochondria, where they exert unknown
      activities. We have studied the isoform A of DMPK, which we have found to be
      prevalently associated to the outer mitochondrial membrane. The kinase activity
      of mitochondrial DMPK protects cells from oxidative stress and from the ensuing
      opening of the mitochondrial permeability transition pore (PTP), which would
      otherwise irreversibly commit cells to death. We observe that DMPK (i) increases
      the mitochondrial localization of hexokinase II (HK II), (ii) forms a multimeric
      complex with HK II and with the active form of the tyrosine kinase Src, binding
      its SH3 domain and (iii) it is tyrosine-phosphorylated by Src. Both interaction
      among these proteins and tyrosine phosphorylation of DMPK are increased under
      oxidative stress, and Src inhibition selectively enhances death in DMPK
      expressing cells after HK II detachment from the mitochondria. Down-modulation of
      DMPK abolishes the appearance of muscle markers in in vitro myogenesis, which is
      rescued by oxidant scavenging. Our data indicate that, together with HK II and
      Src, mitochondrial DMPK is part of a multimolecular complex endowed with
      antioxidant and pro-survival properties that could be relevant during the
      function and differentiation of muscle fibers. 

PMID- 24136223
TI  - The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation
      induced apoptosis and mediates senescence via RSK- and p53-independent
      accumulation of p21WAF1/CIP1.
AB  - The p90 ribosomal S6 kinase (RSK) family is a group of highly conserved Ser/Thr
      kinases that promote cell proliferation, growth, motility and survival. As they
      are almost exclusively activated downstream of extracellular signal-regulated
      kinases 1 and 2 (ERK1/2), therapeutic intervention by RSK inhibition is less
      likely to produce such severe side effects as those observed following inhibition
      of the upstream master regulators Raf, MEK and ERK1/2. Here, we report that BI
      D1870, a potent small molecule inhibitor of RSKs, induces apoptosis, although
      preferentially, in a p21-deficient background. On the other hand, BI-D1870 also
      induces a strong transcription- and p53-independent accumulation of p21 protein
      and protects cells from gamma irradiation (gammaIR)-induced apoptosis, driving
      them into senescence even in the absence of gammaIR. Although we identified p21
      in in vitro kinase assays as a novel RSK substrate that specifically becomes
      phosphorylated by RSK1-3 at Ser116 and Ser146, RNA-interference, overexpression
      and co-immunoprecipitation studies as well as the use of SL0101, another specific
      RSK inhibitor, revealed that BI-D1870 mediates p21 accumulation via a yet unknown
      pathway that, besides its off-site targets polo-like kinase-1 and AuroraB, also
      does also not involve RSKs. Thus, this novel off-target effect of BI-D1870 should
      be taken into serious consideration in future studies investigating the role of
      RSKs in cellular signaling and tumorigenesis. 

PMID- 24136224
TI  - Axonal protection by Nmnat3 overexpression with involvement of autophagy in optic
      nerve degeneration.
AB  - Axonal degeneration often leads to the death of neuronal cell bodies. Previous
      studies demonstrated the crucial role of nicotinamide mononucleotide
      adenylyltransferase (Nmnat) 1, 2, and 3 in axonal protection. In this study,
      Nmnat3 immunoreactivity was observed inside axons in the optic nerve.
      Overexpression of Nmnat3 exerts axonal protection against tumor necrosis factor
      induced and intraocular pressure (IOP) elevation-induced optic nerve
      degeneration. Immunoblot analysis showed that both p62 and microtubule-associated
      protein light chain 3 (LC3)-II were upregulated in the optic nerve after IOP
      elevation. Nmnat3 transfection decreased p62 and increased LC3-II in the optic
      nerve both with and without experimental glaucoma. Electron microscopy showed the
      existence of autophagic vacuoles in optic nerve axons in the glaucoma,
      glaucoma+Nmnat3 transfection, and glaucoma+rapamycin groups, although preserved
      myelin and microtubule structures were noted in the glaucoma+Nmnat3 transfection
      and glaucoma+rapamycin groups. The axonal-protective effect of Nmnat3 was
      inhibited by 3-methyladenine, whereas rapamycin exerted axonal protection after
      IOP elevation. We found that p62 was present in the mitochondria and confirmed
      substantial colocalization of mitochondrial Nmnat3 and p62 in starved retinal
      ganglion cell (RGC)-5 cells. Nmnat3 transfection decreased p62 and increased
      autophagic flux in RGC-5 cells. These results suggest that the axonal-protective
      effect of Nmnat3 may be involved in autophagy machinery, and that modulation of
      Nmnat3 and autophagy may lead to potential strategies against degenerative optic
      nerve disease. 

PMID- 24136225
TI  - FoxO1 controls lysosomal acid lipase in adipocytes: implication of lipophagy
      during nutrient restriction and metformin treatment.
AB  - Finding new molecular pathways and strategies modulating lipolysis in adipocytes
      is an attractive goal of the current research. Indeed, it is becoming clear that
      several human age-related pathologies are caused by adipose tissue expansion and
      altered lipid metabolism. In the present work, we show that transcription factor
      forkhead homeobox type protein O1 (FoxO1) is upregulated by nutrient restriction
      (NR) in adipocytes and exerts the transcriptional control of lipid catabolism via
      the induction of lysosomal acid lipase (Lipa). An increased autophagy and
      colocalization of lipid droplets (LDs) with lysosomes was observed implying
      lipophagy in Lipa-mediated LDs degradation. Interestingly, we found that
      metformin (Metf), a biguanide drug commonly used to treat type-2 diabetes, exerts
      effects comparable to that of NR. Actually, it was able to elicit FoxO1-dependent
      Lipa induction as well as LDs degradation through lipophagy. Moreover, we
      demonstrate that, during NR or Metf treatment, free fatty acids released by Lipa
      are directed toward AMP-activated protein kinase-mediated mitochondrial
      oxidation, thus maintaining energetic homeostasis in adipocytes. In conclusion,
      our data show that lysosomal-mediated lipid catabolism is activated by NR in
      adipocytes and give further support to the use of Metf as a NR mimetic to combat
      age-related diseases associated with altered lipid metabolism. 

PMID- 24136226
TI  - The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than
      enhancing striatal damage, protects striatal neurons from malonate-induced death:
      a potential role of cyclooxygenase-2-dependent metabolism of 2-AG.
AB  - The cannabinoid CB2 receptor, which is activated by the endocannabinoid 2
      arachidonoyl-glycerol (2-AG), protects striatal neurons from apoptotic death
      caused by the local administration of malonate, a rat model of Huntington's
      disease (HD). In the present study, we investigated whether endocannabinoids
      provide tonic neuroprotection in this HD model, by examining the effect of O
      3841, an inhibitor of diacylglycerol lipases, the enzymes that catalyse 2-AG
      biosynthesis, and JZL184 or OMDM169, two inhibitors of 2-AG inactivation by
      monoacylglycerol lipase (MAGL). The inhibitors were injected in rats with the
      striatum lesioned with malonate, and several biochemical and morphological
      parameters were measured in this brain area. Similar experiments were also
      conducted in vitro in cultured M-213 cells, which have the phenotypic
      characteristics of striatal neurons. O-3841 produced a significant reduction in
      the striatal levels of 2-AG in animals lesioned with malonate. However,
      surprisingly, the inhibitor attenuated malonate-induced GABA and BDNF
      deficiencies and the reduction in Nissl staining, as well as the increase in GFAP
      immunostaining. In contrast, JZL184 exacerbated malonate-induced striatal damage.
      Cyclooxygenase-2 (COX-2) was induced in the striatum 24 h after the lesion
      simultaneously with other pro-inflammatory responses. The COX-2-derived 2-AG
      metabolite, prostaglandin E2 glyceryl ester (PGE2-G), exacerbated neurotoxicity,
      and this effect was antagonized by the blockade of PGE2-G action with AGN220675.
      In M-213 cells exposed to malonate, in which COX-2 was also upregulated, JZL184
      worsened neurotoxicity, and this effect was attenuated by the COX-2 inhibitor
      celecoxib or AGN220675. OMDM169 also worsened neurotoxicity and produced
      measurable levels of PGE2-G. In conclusion, the inhibition of 2-AG biosynthesis
      is neuroprotective in rats lesioned with malonate, possibly through the
      counteraction of the formation of pro-neuroinflammatory PGE2-G, formed from COX-2
      mediated oxygenation of 2-AG. Accordingly, MAGL inhibition or the administration
      of PGE2-G aggravates the malonate toxicity.

PMID- 24136227
TI  - Constitutive localization of DR4 in lipid rafts is mandatory for TRAIL-induced
      apoptosis in B-cell hematologic malignancies.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) acts as an
      apoptosis inducer for cancer cells sparing non-tumor cell targets. However,
      several phase I/II clinical trials have shown limited benefits of this molecule.
      In the present work, we investigated whether cell susceptibility to TRAIL
      ligation could be due to the presence of TRAIL death receptors (DRs) 4 and 5 in
      membrane microdomains called lipid rafts. We performed a series of analyses,
      either by biochemical methods or fluorescence resonance energy transfer (FRET)
      technique, on normal cells (i.e. lymphocytes, fibroblasts, endothelial cells), on
      a panel of human cancer B-cell lines as well as on CD19(+) lymphocytes from
      patients with B-chronic lymphocytic leukemia, treated with different TRAIL
      ligands, that is, recombinant soluble TRAIL, specific agonistic antibodies to DR4
      and DR5, or CD34(+) TRAIL-armed cells. Irrespective to the expression levels of
      DRs, a molecular interaction between ganglioside GM3, abundant in lymphoid cells,
      and DR4 was detected. This association was negligible in all non-transformed
      cells and was strictly related to TRAIL susceptibility of cancer cells.
      Interestingly, lipid raft disruptor methyl-beta-cyclodextrin abrogated this
      susceptibility, whereas the chemotherapic drug perifosine, which induced the
      recruitment of TRAIL into lipid microdomains, improved TRAIL-induced apoptosis.
      Accordingly, in ex vivo samples from patients with B-chronic lymphocytic
      leukemia, the constitutive embedding of DR4 in lipid microdomains was associated
      per se with cell death susceptibility, whereas its exclusion was associated with
      TRAIL resistance. These results provide a key mechanism for TRAIL sensitivity in
      B-cell malignances: the association, within lipid microdomains, of DR4 but not
      DR5, with a specific ganglioside, that is the monosialoganglioside GM3. On these
      bases we suggest that lipid microdomains could exert a catalytic role for DR4
      mediated cell death and that an ex vivo quantitative FRET analysis could be
      predictive of cancer cell sensitivity to TRAIL. 

PMID- 24136228
TI  - Src42A modulates tumor invasion and cell death via Ben/dUev1a-mediated JNK
      activation in Drosophila.
AB  - Loss of the cell polarity gene could cooperate with oncogenic Ras to drive tumor
      growth and invasion, which critically depends on the c-Jun N-terminal Kinase
      (JNK) signaling pathway in Drosophila. By performing a genetic screen, we have
      identified Src42A, the ortholog of mammalian Src, as a key modulator of both
      Ras(V12)/lgl(-/-) triggered tumor invasion and loss of cell polarity gene-induced
      cell migration. Our genetic study further demonstrated that the Bendless
      (Ben)/dUev1a ubiquitin E2 complex is an essential regulator of Src42A-induced,
      JNK-mediated cell migration. Furthermore, we showed that ectopic Ben/dUev1a
      expression induced invasive cell migration along with increased MMP1 production
      in wing disc epithelia. Moreover, Ben/dUev1a could cooperate with Ras(V12) to
      promote tumor overgrowth and invasion. In addition, we found that the Ben/dUev1a
      complex is required for ectopic Src42A-triggered cell death and endogenous Src42A
      dependent thorax closure. Our data not only provide a mechanistic insight into
      the role of Src in development and disease but also propose a potential oncogenic
      function for Ubc13 and Uev1a, the mammalian homologs of Ben and dUev1a. 

PMID- 24136229
TI  - Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell
      carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways.
AB  - The DNA-damaging agent camptothecin (CPT) and its analogs demonstrate clinical
      utility for the treatment of advanced solid tumors, and CPT-based
      nanopharmaceuticals are currently in clinical trials for advanced kidney cancer;
      however, little is known regarding the effects of CPT on hypoxia-inducible factor
      2alpha (HIF-2alpha) accumulation and activity in clear cell renal cell carcinoma
      (ccRCC). Here we assessed the effects of CPT on the HIF/p53 pathway. CPT
      demonstrated striking inhibition of both HIF-1alpha and HIF-2alpha accumulation
      in von Hippel-Lindau (VHL)-defective ccRCC cells, but surprisingly failed to
      inhibit protein levels of HIF-2alpha-dependent target genes (VEGF, PAI-1, ET-1,
      cyclin D1). Instead, CPT induced DNA damage-dependent apoptosis that was
      augmented in the presence of pVHL. Further analysis revealed CPT regulated
      endothelin-1 (ET-1) in a p53-dependent manner: CPT increased ET-1 mRNA abundance
      in VHL-defective ccRCC cell lines that was significantly augmented in their VHL
      expressing counterparts that displayed increased phosphorylation and accumulation
      of p53; p53 siRNA suppressed CPT-induced increase in ET-1 mRNA, as did an
      inhibitor of ataxia telangiectasia mutated (ATM) signaling, suggesting a role for
      ATM-dependent phosphorylation of p53 in the induction of ET-1. Finally, we
      demonstrate that p53 phosphorylation and accumulation is partially dependent on
      mTOR activity in ccRCC. Consistent with this result, pharmacological inhibition
      of mTORC1/2 kinase inhibited CPT-mediated ET-1 upregulation, and p53-dependent
      responses in ccRCC. Collectively, these data provide mechanistic insight into the
      action of CPT in ccRCC, identify ET-1 as a p53-regulated gene and demonstrate a
      requirement of mTOR for p53-mediated responses in this tumor type. 

PMID- 24136230
TI  - Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt
      pathway in zebrafish embryos and patients fibroblasts.
AB  - Cornelia de Lange Syndrome is a severe genetic disorder characterized by
      malformations affecting multiple systems, with a common feature of severe mental
      retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A,
      SMC3, and HDAC8) are believed to be responsible for the majority of cases; all
      these genes encode proteins that are part of the 'cohesin complex'. Cohesins
      exhibit two temporally separated major roles in cells: one controlling the cell
      cycle and the other involved in regulating the gene expression. The present study
      focuses on the role of the zebrafish nipblb paralog during neural development,
      examining its expression in the central nervous system, and analyzing the
      consequences of nipblb loss of function. Neural development was impaired by the
      knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with
      increased apoptosis in the developing neural tissues, downregulation of canonical
      Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels.
      Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation
      was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical
      activation of the pathway in nipblb-loss-of-function embryos rescued the adverse
      phenotype and restored the physiological levels of cell death. 

PMID- 24136231
TI  - USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated
      apoptosis.
AB  - Neuroblastoma (NB) is a common pediatric cancer and contributes to more than 15%
      of all pediatric cancer-related deaths. Unlike adult tumors, recurrent somatic
      mutations in NB, such as tumor protein 53 (p53) mutations, occur with relative
      paucity. In addition, p53 downstream function is intact in NB cells with wild
      type p53, suggesting that reactivation of p53 may be a viable therapeutic
      strategy for NB treatment. Herein, we report that the ubiquitin-specific protease
      7 (USP7) inhibitor, P22077, potently induces apoptosis in NB cells with an intact
      USP7-HDM2-p53 axis but not in NB cells with mutant p53 or without human homolog
      of MDM2 (HDM2) expression. In this study, we found that P22077 stabilized p53 by
      inducing HDM2 protein degradation in NB cells. P22077 also significantly
      augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) in NB
      cells with an intact USP7-HDM2-p53 axis. Moreover, P22077 was found to be able to
      sensitize chemoresistant LA-N-6 NB cells to chemotherapy. In an in vivo
      orthotopic NB mouse model, P22077 significantly inhibited the xenograft growth of
      three NB cell lines. Database analysis of NB patients shows that high expression
      of USP7 significantly predicts poor outcomes. Together, our data strongly suggest
      that targeting USP7 is a novel concept in the treatment of NB. USP7-specific
      inhibitors like P22077 may serve not only as a stand-alone therapy but also as an
      effective adjunct to current chemotherapeutic regimens for treating NB with an
      intact USP7-HDM2-p53 axis. 

PMID- 24136232
TI  - Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on
      Runx2-induced osteogenic differentiation.
AB  - Osteoblast differentiation is a pivotal event in bone formation. Runt-related
      transcription factor-2 (Runx2) is an essential factor required for osteoblast
      differentiation and bone formation. However, the underlying mechanism of Runx2
      regulated osteogenic differentiation is still unclear. Here, we explored the
      corresponding mechanism using the C2C12/Runx2(Dox) subline, which expresses Runx2
      in response to doxycycline (Dox). We found that Runx2-induced osteogenic
      differentiation of C2C12 cells results in a sustained decrease in the expression
      of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal
      growth factor (EGF) family. Forced expression of HB-EGF or treatment with HB-EGF
      is capable of reducing the expression of alkaline phosphatase (ALP), a defined
      marker of early osteoblast differentiation. HB-EGF-mediated inhibition of ALP
      depends upon activation of the EGFR and the downstream extracellular signal
      regulated kinase, c-Jun N-terminal kinase mitogen-activated protein kinase
      pathways as well as phosphatidylinositol 3-kinase/Akt pathway. Runx2 specifically
      binds to the Hbegf promoter, suggesting that Hbegf transcription is directly
      inhibited by Runx2. Runx2 can upregulate miR-1192, which enhances Runx2-induced
      osteogenic differentiation. Moreover, miR-1192 directly targets Hbegf through
      translational inhibition, suggesting enhancement of Runx2-induced osteogenic
      differentiation by miR-1192 through the downregulation of HB-EGF. Taken together,
      our results suggest that Runx2 induces osteogenic differentiation of C2C12 cells
      by inactivating HB-EGF-EGFR signaling through the downregulation of HB-EGF via
      both transcriptional and post-transcriptional mechanisms. 

PMID- 24136233
TI  - The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of
      ovarian cancer cells by blocking tubulin polymerization.
AB  - The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to
      mediate the non-genomic action of estrogen in different types of cells and
      tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H
      cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective
      agonist for GPER. G-1 has been shown to induce the expression of genes and
      activate pathways that facilitate cancer cell proliferation by activating GPER.
      Here we demonstrate that G-1 has an anticancer potential with a mechanism similar
      to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1
      blocks tubulin polymerization and thereby interrupts microtubule assembly in
      ovarian cancer cells leading to the arrest of cell cycle in the prophase of
      mitosis and the suppression of ovarian cancer cell proliferation. G-1 treatment
      also induces apoptosis of ovarian cancer cells. The ability of G-1 to target
      microtubules to suppress ovarian cancer cell proliferation makes it a promising
      candidate drug for treatment of ovarian cancer. 

PMID- 24136234
TI  - Calumenin-15 facilitates filopodia formation by promoting TGF-beta superfamily
      cytokine GDF-15 transcription.
AB  - Filopodia, which are actin-rich finger-like membrane protrusions, have an
      important role in cell migration and tumor metastasis. Here we identify 13 novel
      calumenin (Calu) isoforms (Calu 3-15) produced by alternative splicing, and find
      that Calu-15 promotes filopodia formation and cell migration. Calu-15 shuttles
      between the nucleus and cytoplasm through interacting with importin alpha, Ran
      GTPase, and Crm1. The phosphorylation of the threonine at position 73 (Thr-73) by
      casein kinase 2 (CK2) is essential for the nuclear import of Calu-15, and either
      Thr-73 mutation or inhibition of CK2 interrupts its nuclear localization. In the
      nucleus, Calu-15 increases the transcription of growth differentiation factor-15
      (GDF-15), a member of the transforming growth factor-beta (TGF-beta) superfamily,
      via binding to its promoter region. Furthermore, Calu-15 induces filopodia
      formation mediated by GDF-15. Together, we identify that Calu-15, a novel isoform
      of Calu with phosphorylation-dependent nuclear localization, has a critical role
      in promoting filopodia formation and cell migration by upregulating the GDF-15
      transcription. 

PMID- 24136235
TI  - Caspase-generated fragment of the Met receptor favors apoptosis via the intrinsic
      pathway independently of its tyrosine kinase activity.
AB  - The receptor tyrosine kinase Met and its ligand, the hepatocyte growth factor,
      are essential to embryonic development, whereas the deregulation of Met signaling
      is associated with tumorigenesis. While ligand-activated Met promotes survival,
      caspase-dependent generation of the p40 Met fragment leads to apoptosis induction
      - hallmark of the dependence receptor. Although the survival signaling pathways
      induced by Met are well described, the pro-apoptotic signaling pathways are
      unknown. We show that, although p40 Met contains the entire kinase domain, it
      accelerates apoptosis independently of kinase activity. In cell cultures
      undergoing apoptosis, the fragment shows a mitochondrial localization, required
      for p40 Met-induced cell death. Fulminant hepatic failure induced in mice leads
      to the generation of p40 Met localized also in the mitochondria, demonstrating
      caspase cleavage of Met in vivo. According to its localization, the fragment
      induces mitochondrial permeabilization, which is inhibited by Bak silencing and
      Bcl-xL overexpression. Moreover, Met silencing delays mitochondrial
      permeabilization induced by an apoptotic treatment. Thus, the Met-dependence
      receptor in addition to its well-known role in survival signaling mediated by its
      kinase activity, also participates in the intrinsic apoptosis pathway through the
      generation of p40 Met - a caspase-dependent fragment of Met implicated in the
      mitochondrial permeabilization process. 

PMID- 24136236
TI  - Shape design of high drug payload nanoparticles for more effective cancer
      therapy.
AB  - We developed different-shaped drug nanocrystals with similar hydrodynamic sizes
      and surface charges, and found that nanorods exhibited much higher in vitro and
      in vivo anticancer efficacy than that of nanospheres. 

PMID- 24136237
TI  - Visual quality of life in veterans with blast-induced traumatic brain injury.
AB  - IMPORTANCE: Traumatic brain injury (TBI) is an important cause of morbidity
      worldwide, with increasing awareness of the role of blast exposure in military
      and civilian casualties. Visual problems have been reported in TBI and may affect
      functioning and quality of life. OBJECTIVE: To evaluate the 25-item National Eye
      Institute Visual Functioning Questionnaire and Neuro-Ophthalmic Supplement for
      utility in assessing the effect of blast exposure on perceived visual functioning
      among veterans with TBI. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort
      study from a tertiary care Veterans Health Administration hospital. Reported
      visual quality of life was compared with existing norms, and relationships
      between perceived visual quality and ocular injury, diplopia, visual performance,
      and blast exposure characteristics were examined. Participants included
      inpatients with blast-induced TBI who underwent baseline examination between
      December 7, 2006, and January 11, 2012, at a multiple-trauma rehabilitation
      center and who had at least 1 intact eye and were able to undergo psychometric
      testing and ocular examination. Among 64 sequentially eligible patients, 60
      completed visual quality testing, 1 declined study participation, and 3 were
      evaluated prior to inclusion of visual quality testing in the protocol. Thirty
      nine patients returned for outpatient follow-up, with a median test-retest
      interval of 11 months. EXPOSURE: Combat blast exposure with documented TBI. MAIN
      OUTCOMES AND MEASURES: Composite and subscale scores on the 25-item National Eye
      Institute Visual Functioning Questionnaire and Neuro-Ophthalmic Supplement.
      RESULTS: Both tests had high test-retest reliability. Blast-exposed veterans
      reported significantly poorer visual quality compared with healthy samples and
      some patient samples with known eye disease. Scores tended to be worse for
      participants with identified visual performance deficits (poorer visual acuity or
      spatial contrast sensitivity, visual field depression or defects). Scores were
      not related to the extent of ocular injury or to blast exposure characteristics
      such as use of protective eyewear or TBI severity level. CONCLUSIONS AND
      RELEVANCE: Individuals with blast-induced TBI reliably completed both tests and
      reported significant decrements in their subjective visual experiences. Measures
      of subjective visual quality may be useful to identify patients needing
      additional visual or neurologic evaluation and to monitor the effect of visual
      rehabilitation on patients with blast-related visual disabilities.

PMID- 24136238
TI  - Targeted topical and combination laser surgery for the treatment of
      angiofibromas.
AB  - BACKGROUND AND OBJECTIVE: The angiofibromas of Tuberous sclerosis (TS) is well
      described manifestation. Due to the progressive nature of the skin lesion, a safe
      and effective technique for treating these disfiguring skin lesions is needed.
      STUDY DESIGN/PATIENTS AND METHODS: We report a targeted topical and combination
      laser technique for treating the angiofibromas of TS in one patient. This
      includes treatment with topical sirolimus, pinpoint electrosurgery, pulsed-dye
      laser treatment, and ablative fractional resurfacing (AFR). RESULTS: Improvement
      in the number and appearance of facial angiofibromas and erythema is noted,
      without scarring or adverse events. CONCLUSION: The technique of targeted therapy
      with sirolimus with electrosurgery, pulsed dye laser treatment, and AFR
      represents an innovative, safe therapeutic option for treating facial
      angiofibromas associated with TS.

PMID- 24136239
TI  - Photodynamic therapy for management of cervical intraepithelial neoplasia II and
      III in young patients and obstetric outcomes.
AB  - OBJECTIVE: To evaluate the response and efficacy of photodynamic therapy (PDT)
      with or without loop electrosurgical excision procedure (LEEP)/conization (Cone)
      to preserve fertility in young patients with cervical intraepithelial neoplasia
      (CIN) II and III. METHODS: We reviewed the medical records of patients with CIN
      who had been treated by PDT. Among a total of 73 patients who received PDT for
      CIN II/III between September 2000 and August 2011, 59 patients aged 40 or younger
      and who wished to preserve fertility were included. Patients were divided into
      four groups: group (I) only PDT without LEEP (n = 13), group (II) PDT combined
      with LEEP/Cone (n = 15), group (III) PDT due to positive LEEP/Cone margin (n =
      25), group (IV) PDT for recurrent CIN after LEEP/Cone (n = 6). Surface
      photoillumination with red laser light at a wavelength of 630 nm was applied to
      the uterine cervix and endocervical canal of patients 48 hours after an
      intravenous injection of 2 mg/kg of photosensitizer. RESULTS: The median age of
      the 59 patients (CIN 2: 4, CIN 3: 22, carcinoma in situ: 31, adenocarcinoma in
      situ: 2) was 30.4 years. Twenty-two patients were unmarried and 38 were
      nulliparous. The complete remission (CR) rate was 98.1% (52/53) at 1 year follow
      up except six patients followed up loss. The remaining one had recurred at 1 year
      after PDT, and one residual case at 3 months follow-up was regarded as CR showing
      NED after secondary PDT. Human papilloma virus (HPV) typing was performed. Before
      treatment HPV infection rate was 96.3% (52/54). HPV DNA could be no longer
      detected in 89.8% (44/49) and 87.0% (40/46) at 3 and 12 months after PDT. Among
      29 patients who tried to be pregnant, 18 patients achieved 25 pregnancies (6
      abortions, 1 ectopic, 1 preterm, 15 term, and 2 ongoing pregnancies.) There has
      been no fetal loss due to incompetent internal os of cervix. For adverse events,
      photosensitivity occurred in 13.6% (8/59) and cervical stenosis occurred in one
      patient. CONCLUSIONS: PDT combined with or without LEEP/Cone may be a potential
      alternative for effective conservative treatment of CIN in young patients who
      wish to preserve fertility.

PMID- 24136241
TI  - Genes in the serotonin pathway are associated with bipolar affective disorder in
      a Han Chinese population.
AB  - Serotonin plays an important role in mood regulation, but the involvement of
      serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood
      disorder, is not clear. We selected 21 single-nucleotide polymorphisms (SNPs)
      within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for
      genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP
      I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and
      rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were
      significantly associated with BP-I, both genotype-wise and allele-wise.
      Furthermore, a specific haplotype in the HTR2A gene showed a significant
      association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the
      serotonin pathway play important roles in susceptibility to BP-I.

PMID- 24136242
TI  - Role of the PTEN signaling pathway in autism spectrum disorder.
AB  - Autism is an etiologically heterogeneous group of neurodevelopmental disorders,
      diagnosed mostly by the clinical behavioral phenotypes. The concept that the
      tumor-related gene PTEN plays a critical role in autism spectrum disorder has
      emerged over the last decade. In this review, we focus on the essential role of
      the PTEN signaling pathway in neuronal differentiation and the formation of
      neural circuitry, as well as genetic mouse models with Pten manipulations.
      Particularly, accumulated data suggest that the effect of PTEN on neural stem
      cell development contributes significantly to the pathophysiology of autism
      spectrum disorders. 

PMID- 24136243
TI  - Dysregulation of synaptic and extrasynaptic N-methyl-D-aspartate receptors
      induced by amyloid-beta.
AB  - The toxicity of amyloid-beta (Abeta) is strongly associated with Alzheimer's
      disease (AD), which has a high incidence in the elderly worldwide. Recent
      evidence showed that alteration in the activity of N-methyl-D-aspartate receptors
      (NMDARs) plays a key role in Abeta-induced neurotoxicity. However, the activation
      of synaptic and extrasynaptic NMDARs has distinct consequences for plasticity,
      gene regulation, neuronal death, and Abeta production. This review focuses on the
      dysregulation of synaptic and extrasynaptic NMDARs induced by Abeta. On one hand,
      Abeta downregulates the synaptic NMDAR response by promoting NMDAR endocytosis,
      leading to either neurotoxicity or neuroprotection. On the other hand, Abeta
      enhances the activation of extrasynaptic NMDARs by decreasing neuronal glutamate
      uptake and inducing glutamate spillover, subsequently causing neurotoxicity. In
      addition, selective enhancement of synaptic activity by low doses of NMDA, or
      reduction of extrasynaptic activity by memantine, a non-competitive NMDAR
      antagonist, halts Abeta-induced neurotoxicity. Therefore, future neuroprotective
      drugs for AD should aim at both the enhancement of synaptic activity and the
      disruption of extrasynaptic NMDAR-dependent death signaling. 

PMID- 24136245
TI  - Evaluation of total phenolics, flavonoids and antioxidant activity of 18 Korean
      onion cultivars: a comparative study.
AB  - BACKGROUND: Onion is undoubtedly one of the major sources of flavonoids. However,
      there exists a varietal difference in composition, concentration and beneficial
      activities of onion, on the basis of cultivars, day length sensitivity/ripening
      and types. To characterise such differences, 18 onion cultivars from Korean were
      evaluated for their total phenolics, flavonoids and antioxidant activity.
      Simultaneous quantification of quercetin, quercetin-3,4'-O-diglucoside, quercetin
      4'-O-monoglucoside and isorhamnetin-3-glucoside was made in methanol and 75%
      ethanol. RESULTS: Total phenolic content was examined spectrophotometrically with
      the Folin-Ciocalteu phenol reagent and total antioxidant activity were studied by
      the ferric reducing antioxidant power (FRAP) and diphenyl picryl hydrazyl (DPPH)
      methods. The cultivar 'Sunpower' showed the highest level of total phenolics
      [5016 +/- 30.0 ug gallic acid equivalents g(-1) dry weight (DW)] and flavonoids
      (2873.95 +/- 60.01 ug Q g(-1) DW) among the 18 cultivars in methanol. However,
      there were fewer total phenolics and flavonoids in ethanol extracts. The
      antioxidant activity for cultivar Sunpower was highest in ethanol extracts 24.12
      +/- 1.00 and 16.13 +/- 0.35 umol L(-1) Trolox equivalents g(-1) DW with FRAP and
      DPPH, respectively. CONCLUSION: Among the 18 cultivars, Sunpower is the most
      promising in terms of total phenolics, total flavonoids and antioxidant activity.
      Our results suggest that day length sensitivity/ripening among the cultivars do
      not play any significant role for high values of total phenolics, flavonoids and
      antioxidant activity.

PMID- 24136244
TI  - Hyposmia: a possible biomarker of Parkinson's disease.
AB  - Hyposmia, identified as reduced sensitivity to odor, is a common non-motor
      symptom of Parkinson's disease (PD) that antedates the typical motor symptoms by
      several years. It occurs in ~90% of early-stage cases of PD. In addition to the
      high prevalence, the occurrence of hyposmia may also predict a higher risk of PD.
      Investigations into hyposmia and its relationship with PD may help elucidate the
      underlying pathogenic mechanisms. This review provides an update of olfactory
      dysfunction in PD and its potential as a biomarker for this devastating disease. 

PMID- 24136246
TI  - Eating disorders: a hidden phenomenon in outpatient mental health?
AB  - BACKGROUND: Eating disorders are common but underdiagnosed illnesses. Help
      seeking for co-occurring issues, such as anxiety and depression, are common.
      OBJECTIVES: To identify the prevalence of eating problems, using the SCOFF, and
      eating disorders when screening positive on the SCOFF (i.e., >=2), among patients
      seeking help for anxiety and depression at a community-based mental health
      service. METHOD: Patients (N = 260) consecutively referred and assessed for
      anxiety and depression treatment were administered the SCOFF screening
      questionnaire and a semi-structured standardized diagnostic interview during
      routine intake. RESULTS: 18.5% (48/260) scored >=2 on the SCOFF, indicating
      eating problems. Of these, 41% (19/48) met criteria for an eating disorder. Thus,
      overall, 7.3% (19/260) of the sample met criteria for a DSM-IV eating disorder.
      Those scoring >=2 on the SCOFF were more likely to: be female (p = 0.001),
      younger (p = 0.003), and have a history of self-harm (p < 0.001). DISCUSSION:
      This study confirms that eating disorders are a hidden phenomenon in general
      outpatient mental health. By using a standardized diagnostic interview to
      establish diagnosis rather than self- or staff-report, the study builds on
      limited previous findings. The naturalistic study setting shows that screening
      for eating disorders can be easily built into routine intake practice, and
      successfully identifies treatment need.

PMID- 24136247
TI  - Deportation history among HIV-positive Latinos in two US-Mexico border
      communities.
AB  - Health-related vulnerabilities associated with deportation are understudied. We
      conducted a cross-sectional study to identify factors associated with history of
      deportation from the US to Mexico among HIV-positive Latinos. From 2009 to 2010,
      we recruited a convenience sample from HIV clinics in San Diego, US and Tijuana,
      Mexico. Of 283 participants, 25% reported a prior deportation. Factors
      independently associated with increased odds of deportation history were being
      male [adjusted odds ratio (AOR) 2.77; 95% CI 1.18-6.48], having <=high-school
      education (AOR 3.87; 95% CI 1.84-8.14), ever using cocaine (AOR 2.46; 95% CI 1.33
      4.57), and reporting personalized HIV-stigma: "some have told me HIV is what I
      deserve for how I lived" (AOR 2.23; 95% CI 1.14-4.37). Lower self-reported
      antiretroviral medication adherence (AOR 0.35; 95% CI 0.12-0.96) and perceiving
      HIV-stigma: "most people believe a person who has HIV is dirty" (AOR 0.49; 95% CI
      0.25-0.94) were associated with decreased odds of deportation history.
      Deportation is associated with specific socioeconomic indicators that are known
      to impact the health of individuals living with HIV.

PMID- 24136248
TI  - Development and validation of an UHPLC-LTQ-Orbitrap MS method for non-anthocyanin
      flavonoids quantification in Euterpe oleracea juice.
AB  - Euterpe oleracea fruits have gained much attention because of their phenolic
      constituents that have shown potential health benefits. The aim of this work was
      to quantify the major non-anthocyanin flavonoids (NAF) in the fruit juice by an
      accurate method coupling ultra-high pressure liquid chromatography with a linear
      ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap
      MS). Fruits were processed to juice, and then the juice was lyophilized and
      defatted. The residue was then extracted in the presence of methanol by
      sonication. The extraction time was optimized and recovery rates of the
      extraction were >90%. The extracts were dried and solubilized again in 40% MeOH,
      which showed the best compromise for MS detection. For the UHPLC quantification,
      a HSS C18 column (1.8 MUm) was used with a gradient elution of methanol and water
      both with 0.1% formic acid. Total error and accuracy profiles were used as
      validation criteria. Seven compounds and their isomers were successfully
      separated, including the major NAF. Calibration in the matrix was found to be
      more accurate than calibration without matrix. Trueness (<15% relative bias),
      repeatability, and intermediate precision (<13% RSD), selectivity, response
      function, linearity, LOD (ranged from 0.04 to 0.81 MUg/mL) and LOQ (0.15-5.78
      MUg/mL) for 12 compounds were evaluated and the quantification method was
      validated. Its applicability was demonstrated on real samples from different
      suppliers. Their qualitative and quantitative profiles were similar and some
      compounds were for the first time quantified. In addition, eriodictyol was
      identified for the first time in this fruit along with five other flavonoids for
      which possible structures were proposed.

PMID- 24136249
TI  - Comparison between GC-MS and GC-ICPMS using isotope dilution for the simultaneous
      monitoring of inorganic and methyl mercury, butyl and phenyl tin compounds in
      biological tissues.
AB  - The aim of this work is to compare simultaneous isotope dilution analysis of
      organotin and organomercury compounds by gas chromatography-mass spectrometry (GC
      MS) and gas chromatography-inductively coupled plasma mass spectrometry (GC
      ICP/MS) on certified bivalve samples. These samples were extracted by microwave
      with tetramethylammonium hydroxide (TMAH). Derivatization with both NaBEt4 and
      NaBPr4 was evaluated, and analytical performances were compared. Two CRM
      materials, BCR-710 and CRM-477, were analyzed by both techniques to verify
      accuracy. A mixed spike containing (201)Hg-enriched methylmercury (MeHg), (199)Hg
      enriched inorganic mercury (iHg), (119)Sn-enriched monobutyltin (MBT), dibutyltin
      (DBT), and tributyltin (TBT) as well as homemade (116)Sn-enriched monophenyltin
      (MPT), diphenyltin (DPT), and triphenyltin (TPT) was used for the isotope
      dilution analysis of samples. The two techniques studied were compared in terms
      of classic analytical parameters: linearity, precision or repeatability (i.e.,
      percent relative standard deviation, RSD%), limit of detection (LOD), and limit
      of quantification (LOQ), showing excellent linearity, precision below 12% for all
      analytes, and LOQs of 0.06-1.45 pg for GC-MS and 0.02-0.27 pg for GC-ICP/MS.

PMID- 24136250
TI  - Recent developments in stir bar sorptive extraction.
AB  - As a crucial step in qualitative and quantitative analysis, sample pretreatment
      is commonly used to isolate the target analytes, concentrate them, or convert
      them into the forms tailored to the instrumental analysis. In recent years, there
      has been a trend for sample pretreatment techniques to become more miniaturized
      and more environmentally friendly. Stir bar sorptive extraction (SBSE), which was
      developed in 1999, is such an environmentally friendly microextraction technique.
      Compared with other microextraction techniques, including solid phase
      microextraction and liquid phase microextraction, SBSE provides a higher
      extraction efficiency and better reproducibility owing to the much greater amount
      of the extraction phase, and no special skills are required. However, there are
      some problems associated with SBSE, such as the limited applicable coatings,
      coating abrasion of the laboratory-made stir bar, and the difficulty in
      automation, which restrict the further improvement and application of SBSE. This
      review focuses on the development of SBSE in the past decade, in terms of coating
      preparation, automated systems, novel extraction modes, its use with various
      instruments, and applications in food, environmental, and biological samples. 

PMID- 24136252
TI  - Optical spectroscopic methods for intraoperative diagnosis.
AB  - Molecular analytical methods are increasingly needed for a quick and reliable
      analysis of tissue in an operating room to provide more information during
      operations. In this Trends article, we highlight the current state and the
      developments of optical spectroscopic methods as intra operative tools. The
      clinical problem and challenges are illustrated on the example of brain tumor
      surgery. While fluorescence microscopy is already used, vibrational spectroscopy
      techniques will complement the standard method for brain tissue diagnostics. New
      portable instruments are currently available and can be stationed in the
      operating room for quick evaluation of tissue. The promise and limitations of
      fluorescence and vibrational spectroscopy as intraoperative tools are surveyed in
      this report. 

PMID- 24136253
TI  - The application of carbon-14 analyses to the source apportionment of atmospheric
      carbonaceous particulate matter: a review.
AB  - Organic carbon (OC) and elemental carbon (EC) together constitute a substantial
      proportion of airborne particulate matter (PM). Insight into the sources of this
      major contributor to PM is important for policies to mitigate the impact of PM on
      human health and climate change. In recent years measurement of the abundance of
      the radioisotope of carbon ((14)C) in samples of PM by accelerator mass
      spectrometry has been used to help quantify the relative contributions from
      sources of fossil carbon and contemporary carbon. This review provides an
      introduction to the different sources of carbon within PM and the role of (14)C
      measurements, a description of the preparation of PM samples and of the
      instrumentation used to quantify (14)C, and a summary of the results and source
      apportionment methods reported in published studies since 2004. All studies
      report a sizable fraction of the carbonaceous PM as of non-fossil origin. Even
      for PM collected in urban locations, the proportions of non-fossil carbon
      generally exceed 30%; typically the proportion in urban background locations is
      around 40-60% depending on the local influence of biomass burning. Where values
      have been measured directly, proportions of non-fossil carbon in EC are lower
      than in OC, reflecting the greater contribution of fossil-fuel combustion to EC
      and the generally small sources of contemporary EC. Detailed source apportionment
      studies point to important contributions from biogenic-derived secondary OC,
      consistent with other evidence of a ubiquitous presence of heavily oxidized
      background secondary OC. The review concludes with some comments on current
      issues and future prospects, including progress towards compound-class and
      individual-compound-specific (14)C analyses.

PMID- 24136254
TI  - Stability and efficiency of supported liquid membranes in electromembrane
      extraction--a link to solvent properties.
AB  - The current work presents a large systematic screening of 61 possible organic
      solvents used as supported liquid membranes (SLM) in electromembrane extraction
      (EME). For each organic solvent, recovery, current across the SLM, and stability
      considerations have been investigated and correlated to relevant solvent
      properties through partial least square regression analysis. The five unpolar
      basic drugs pethidine, haloperidol, methadone, nortriptyline, and loperamide were
      used as model analytes. Efficient EME solvents were found to have a low water
      solubility (<0.5 g L(-1)) and belonged to cluster 2 of a Kamlet-and-Taft-based
      solvent classification system (high dipole moments and proton acceptor
      properties). These parameters were especially found in nitroaromatic compounds
      and ketones. Small molecules with low log P value and high water solubility were
      unsuitable, as they tended to give unstable extractions, caused by a high current
      across the SLM. This was often combined with substantial solvent-related
      interferences and the generation of an electroosmotic flow across the SLM, with
      resulting acceptor solution expansion. Large molecules with a high log P value
      were classified as inefficient. For these solvents, no current was measured
      across the SLM and no analytes were extracted. This is the first time systematic
      knowledge on the SLM in EME has been gathered and investigated, and the presented
      results could be highly beneficial for future development and optimization of
      EME.

PMID- 24136255
TI  - N-terminal in coat protein of Garlic virus X is indispensible for its serological
      detection.
AB  - Conserved coat protein region of plant viruses is often used as source of antigen
      for production of polyclonal antibodies for broad-based detection of closely
      related viruses. Antigenic region in coat protein is located either on N
      terminal, and/or C-terminal or in the middle of coat protein. A study was
      undertaken to determine if antigenic region resides in N-terminal in Garlic virus
      X (GarV-X) of Allexivirus. In allexiviruses, N-terminal of coat protein region (1
      57 amino acids) was highly variable. A complete coat protein of 27 kDa and a
      truncated protein without N-terminal (20 kDa) of GarV-X were expressed in pET
      expression vector and confirmed in western blotting using anti-His antisera.
      These expressed proteins were purified and used for antisera production. Specific
      and strong reaction was obtained for antisera generated against GarV-X full CP
      and GarV-X was detected in field-grown allium crops viz., onion, garlic, leek,
      and bunching onion and chives in ELISA. Antisera against GarV-X CPDelta1-61
      (truncated CP) did not show reaction for GarV-X detection in immunoassay. Epitope
      mapping also indicated N-terminal as major antigenic determinant region with
      highest antigenic signal score. Our studies confirm that antigenic signals or
      epitopes reside in the N-terminal region of GarV-X which can be synthesized and
      used for production of monoclonal antibodies for specific detection purposes.

PMID- 24136256
TI  - [Pain assessment of biological conduit small gap tubulization in rat sciatic
      nerve multilation model].
AB  - OBJECTIVE: To explore the pain sensation recovery discipline of 2 mm small gap
      biological conduit tubulization and epineurial neurorrhaphy in rat sciatic nerve
      multilation model. METHODS: Based on the rat sciatic nerve multilation model, 2
      mm small gap biological conduit tubulization and epineurial neurorrhaphy were
      applied and the 50% paw withdrawal threshold was observed after 2, 4, 5, 6, 8 and
      12 weeks. The data were analyzed by two-way ANOVA and chi-square criterion.
      RESULTS: Obvious hyperalgesia was observed in week 2 in both experimental group
      and control group, and 50% paw withdrawal threshold was improved significantly
      even to 15 g. The 50% paw withdrawal threshold began to decline week 4 and the
      50% paw withdrawal threshold of small gap tubulization group was obviously lower
      than that of control group, which may imply that the pain sensation recovery of
      small gap tubulization group was earlier than that of control group. The 50% paw
      withdrawal threshold of small gap tubulization group began to increase to the
      plateau period [week 5: (12.70 +/- 5.64) g; week 6: (12.20 +/- 3.26) g; week 8:
      (12.31 +/- 4.19) g; week 12: (13.95 +/- 2.58) g]. The 50% paw withdrawal
      threshold of control group declined gradually [week 5: (10.47 +/- 7.02) g; week
      6: (9.42 +/- 6.86) g; week 8: (8.50 +/- 7.15) g; week 12: (8.06 +/- 5.93) g]. The
      difference was statistical significant between small gap tubulization group and
      control group in 12th week. CONCLUSION: Compared with the traditional epineurial
      neurorrhaphy for peripheral nerve multilation, 2 mm small gap biological conduit
      tubulization can improve the 50% paw withdrawal threshold during peripheral nerve
      regeneration process and reduce the pain incidence.

PMID- 24136257
TI  - [Anatomical evaluation and clinical significance of lateral ankle ligament].
AB  - OBJECTIVE: To measure anatomy of anterior talofibular ligament (ATFL) and
      calcaneofibular ligament (CFL) and their relationship to adjacent osseous
      structures, in order to provide anatomical reference to surgical procedures.
      METHODS: Twenty-six human ankle cadavers were used in this study. The mean value
      of length, insertion width, insertion angle and distance to adjacent osseous
      structures were measured. RESULTS: The lengths of ATFL and CFL were (20.08 +/-
      2.16) mm and (32.72 +/- 9.17) mm. The width of ATFL were (8.75 +/- 1.8) mm
      (proximal) and (9.26 +/- 1.34) mm (distal) respectively. The distance of distal
      ATFL footprint to the upper-surface of talus neck were (12.92 +/- 0.93) mm, the
      distance of proximal ATFL footprint to fibular tip were (11.44+/-0.61) mm. The
      width of CFL were (4.76 +/- 0.62) mm (proximal) and (5.08 +/- 0.77) mm (distal)
      respectively. The distance of proximal CFL footprint to fibular tip were (3.74 +/
      0.55) mm, The distance of distal CFL footprint to the surface of subtalar joint
      were (12.62 +/- 2.08) mm. The insertion angle with fibular axis in lateral view
      of ATFL and CFL were 81 degrees  +/- 11 degrees and 47 degrees  +/- 16 degrees 
      respectively. ATFL in anterioposterior view had 67 degrees  +/- 7 degrees  angle
      with fibular axis. CONCLUSION: The length and width of ATFL and CFL were
      relatively constant. The lateral insertion angle was relatively with large
      variation. These data may provide reference for reconstructing lateral ankle
      ligaments.

PMID- 24136258
TI  - [Central placement of screw fixation for scaphoid fracture: a biomechanical
      study].
AB  - OBJECTIVE: To evaluate the effect to the fixation stability of central screw
      placement during scaphoid fracture surgery. METHODS: We designed oblique
      osteotomies for 32 identical sawbone scaphoids and fixed each specimen with a
      cannulated screw. Sawbone scaphoids were divided into 4 groups, according to
      position of the osteotomy (distal waist portion or proximal waist portion) and
      the position of the screw (central or eccentric). We performed Computed
      Tomography scanning to one specimen, and then the central zone of the scaphoid
      was established from volume data by using the preoperative planning system
      software (VxWork 4.0). The position of the osteotomy plane, the entrance and exit
      points of the screw guide pin were designed on the software as well. We placed
      the specimens under the increasing load of a pneumatically driven plunger to
      compare the load to failure and the distance at failure between the central and
      eccentric screw groups. RESULTS: In general, we found the statistical differences
      of the load to failure and the displacement of fracture between the groups
      (F=31.485,P=0.001; F=33.328,P=0.018). The average load to failure and fracture
      displacement was more statistically different in the central group [(80.82 +/-
      15.63) N, (2.3 +/- 0.5) mm] for proximal waist fracture than in the eccentric
      group [(58.32 +/- 17.18) N, (3.1 +/- 0.5) mm]. As to the distal waist fracture,
      the average load to failure and fracture displacement was better in the central
      group [(76.83 +/- 14.54) N, (2.2 +/- 0.7) mm] than in the eccentric group [(70.38
      +/- 13.32) N, (2.5 +/- 0.6) mm] without significant difference. CONCLUSION: In
      this biomechanical model of an unstable oblique scaphoid fracture, we find that
      higher stability of fixation has been achieved with a screw placed centrally in
      the scaphoid, compared with a screw peripherally placed.

PMID- 24136259
TI  - [Comparative analysis of the clinical characteristics of orthopedic inpatients in
      Lushan and Wenchuan earthquakes].
AB  - OBJECTIVE: To systematically analyze and compare the clinical characteristics of
      orthopedic inpatients in Lushan and Wenchuan earthquake, so as to provide useful
      references for future earthquakes injury rescue. METHODS: Based on the orthopedic
      inpatients in Lushan and Wenchuan earthquakes, the data of the age, gender,
      injury causes, body injured parts and speed of transport were classified and
      compared. RESULTS: The duration of patients admitted to hospital lasted long and
      the peak appeared late in Wenchuan earthquake, which is totally opposed to Lushan
      earthquake. There was no significant difference in the patient's age and gender
      between the two earthquakes. However, the occurrence rate of crush syndrome,
      amputation, gas gangrene, vascular injury and multiple organ dysfunction syndrome
      (MODS) in Wenchuan earthquake was much higher than that in Lushan earthquake.
      Blunt traumas or crush-related injuries (79.6%) are the major injury cause in
      Wenchuan earthquake, however, high falling injuries and falls (56.8%) are much
      higher than blunt trauma or crush-related injuries (39.2%) in Lushan earthquake.
      The incidence rate of foot fractures, spine fractures and multiple fractures in
      Lushan earthquake was higher than that in Wenchuan earthquake, but that of open
      fractures and lower limb fractures was lower than that in Wenchuan earthquake.
      CONCLUSION: The rapid rescue scene is the cornerstone of successful treatment,
      early rescue and transport obviously reduce the incidence of the wound infection,
      crush syndrome, MODS and amputation. Popularization of correct knowledge of
      emergency shelters will help to reduce the damage caused by blindly jumping or
      escaping while earthquake happens.

PMID- 24136260
TI  - [Effect of cement implantation and pressor agents in hip replacement on blood
      pressure].
AB  - OBJECTIVE: To discuss the change of blood pressure involved by pressor agents
      after the implantation of cement in hip replacement. METHODS: A total of 172
      cases of femoral neck fracture underwent hip replacement in Department of
      Orthopedics and Trauma, Peking University People's Hospital between July 2008 and
      July 2013 were involved in this retrospective study. The blood pressure and usage
      of pressor agents were recorded before and after bone cement implantation. The
      data of blood pressure and usage of agents were collected according to anesthesia
      records. All the cases were divided into four groups by the application of
      pressor agents: Free of using agent group (Free-agent group), agents used before
      implantation of cement group (Pre-agent group), agents used after implantation of
      cement group (Post-agent group) and agent used before & after implantation of
      cement group (Pre and Post-agent group). Further statistic analysis was then
      performed. RESULTS: Free-agent group's mean systolic blood pressure decreased for
      (4.0 +/- 10.3) mmHg. The decreasing was significant (t=3.660, P=0.000). Free
      agent group's mean diastolic blood pressure decreased (1.3 +/- 7.5) mmHg. The
      decreasing was not significant (t=2.286, P=0.149). Pre-agent group's mean
      systolic blood pressure decreased for (0.5 +/- 20.2) mmHg. The decreasing was not
      significant (t=0.114, P=0.911). Pre-agent group's mean diastolic blood pressure
      increased (0.7 +/- 10.2) mmHg. The increasing was not significant (t=-0.316,
      P=0.756). Post-agent group's mean systolic blood pressure decreased for (6.9 +/-
      15.0) mmHg. The decreasing was significant (t=3.195, P=0.002). Post-agent group's
      mean diastolic blood pressure decreased (3.6 +/- 7.4) mmHg. The decreasing was
      significant (t=3.407,P=0.001). Pre & Post-agent group's mean systolic blood
      pressure decreased for (5.0 +/- 12.2) mmHg. The decreasing was not significant
      (t=1.667, P=0.115). Pre & Post-agent group's mean diastolic blood pressure
      increased (1.3 +/- 8.5) mmHg. The increasing was not significant (t=-0.656,
      P=0.521). CONCLUSION: Implantation of cement in hip replacement surgery causes
      blood pressure decreasing. The application of pressor agents before cement
      implantation can stabilize blood presure and shorten the period of hypotension.

PMID- 24136261
TI  - [Segmental schwannomatosis in upper-extremity: 5 cases report and literature
      review].
AB  - OBJECTIVE: Multiple schwannomas localized in a single body part not crossing the
      midline constitute a rare variant of neurofibromatosis, segmental
      schwannomatosis. We report our experience with 5 cases of segmental
      schwannomatosis of the upper extremity and review the related literature to
      improve our skills in diagnosis and differentiation. METHODS: Five patients with
      segmental schwannomatosis received surgical treatment in our department from 2003
      to 2012, of whom 4 were female and the other one male. The mean age was 38 years,
      ranging from 29 to 48 years. In retrospect, we discussed the clinical appearance,
      histologic characteristics, genetic data and surgical management. RESULTS: A
      total of 351 patients with schwannomas were treated in the recent decade. There
      were 326 patients with solitary schwannoma, accounting for 92.88%, 25 with
      neurofibromatosis type 2 (NF-2), occupying 7.12% and 5 with segmental
      schwannomatosis representing 1.42% of the total. Schwannomas are limited in one
      upper extremity and randomly located at ulnar nerve, median nerve and radial
      nerve and their branches, with no obvious predisposition. Their family history
      was negative for cutaneous tumors or central nervous system disease. Neurological
      examinations did not reveal symptoms related to vestibular nerves or optic
      nerves, which excluded NF-2 preliminarily. The prior symptom of three cases was
      pain which could be irradiated to the nerve distribution area. No pain but slight
      numbness was found in two cases. MRI disclosed multiple masses along the course
      of the nerves. They were isointense to muscle on T1-weighed images and
      hyperintense to subcutaneous fat on T2-weighed images. All schwannomas were
      resected and histological sections exhibited a characteristic feature of
      schwannoma. Follow-up work of 4.5 years was done to 4 cases and no recurrence or
      impairment of nerves was found. CONCLUSION: Segmental schwannomatosis is
      characterized by multiple schwannomas localized in one limb (upper extremity in
      our cases) without vestibular nerve tumors, most frequently seen in females at
      the age of 30-60 years. Segmental schwannomatosis is rarely seen in the previous
      literature. We found around 20 cases in English articles and no cases in domestic
      articles. In consideration of the clinical appearances of these 5 cases and the
      genetic research in the related literature, we recommend that segmental
      schwannomatosis is a distinct form of neurofibromatosis which needs to be more
      studied. We should also pay more attention to differentiating this disease from
      other forms of neurofibromatosis.

PMID- 24136262
TI  - [Surgical treatment of deltoid ligament injury associated with ankle fractures].
AB  - OBJECTIVE: To observe the clinical outcome after the surgical treatment of the
      deltoid ligament injury associated with ankle fractures. METHODS: From January
      2005 to December 2009, 16 deltoid ligament ruptures associated with ankle
      fractures were repaired. According to the AO/OTA system, 2 cases belonged to
      fracture A, 8 to B, and 6 to C. Radiographs, American Orthopaedic Foot and Ankle
      Society (AOFAS) ankle-hindfoot scores and visual analogue scale (VAS) were used
      for the outcome measurements. RESULTS: The 16 patients were followed up for 30 to
      84 months,with the mean follow-up of 47 months. All wounds healed at the first
      stage. The mean time of bone union was 12.8 weeks (range: 10-14 weeks). The mean
      AOFAS ankle-hindfoot score in the last follow-up was 93 points (range: 85-100
      points). The mean score of VAS was 0.94 points (range: 0-2 points). CONCLUSION:
      Surgical treatment of ankle fractures associated with deltoid ligament rupture
      can achieve satisfactory outcomes, but it is important to decide the operation
      indication.

PMID- 24136263
TI  - [Prognosis of calf deep-vein thrombosis after total knee arthroplasty].
AB  - OBJECTIVE: To explore the outcome of deep-vein thrombosis (DVT) in the calf after
      total knee arthroplasty. METHODS: From June 2009 to June 2011, 159 patients with
      DVT in the calf after total knee arthroplasty (TKA) were divided into two groups.
      Group A (active mobilization) included 80 patients and group B (passive
      mobilization) 79 patients. These patients were checked with ultrasonography 1
      week and 4 weeks postoperation. The changes of DVT in the calf, ROM, KSS score
      and WOMAC score were observed. RESULTS: The disappearance rates of the calf DVT
      in groups A and B were 35% and 33% 4 weeks postoperation. There was similar DVT
      disappearance rate in the two groups (P=0.91 ). No patient developed proximal
      propagation. There was no difference of the ROM (111.9 degrees  +/- 13.4 degrees 
      vs. 110.5 degrees  +/- 10.9 degrees , P=0.490), KSS knee score ( 93.5 +/- 4.7 vs.
      93.9 +/- 5.1, P=0.621), KSS function score (83.4 +/- 15.1 vs. 82.9 +/- 14.5,
      P=0.513) and WOMAC score (90.9 +/- 5.7 vs. 90. 3 +/- 6.1, P=0.535) in groups A
      and B. CONCLUSION: A DVT in the calf after TKA can resorb spontaneously with
      time. The treatment of a DVT in the calf does not need additional
      anticoagulation.

PMID- 24136264
TI  - [Comparison of curative effects between minimally invasive locking plate internal
      fixation and open reduction with internal fixation for the treatment of proximal
      humerus fractures].
AB  - OBJECTIVE: To investigate the comparison of curative effects in treating proximal
      humerus fractures' patients between minimally invasive locking plate internal
      fixation and open reduction with internal fixation, and to provide guidance for
      the operation method of the proximal humerus fracture patients. METHODS: In the
      study, 157 patients of proximal humerus fractures from May 2006 to December 2012
      in Peking University Third Hospital were analyzed retrospectively, of whom 78
      were followed up, including 19 males and 59 females. They were from 15 to 90
      years old, with the mean age of 60.5 years. According to Neer classification,
      there were 53 cases of two-part fractures, 19 cases of three-part fractures and 6
      cases of four-part fractures. According to AO classification, there were 49 cases
      of type A,21 cases of type B and 8 cases of type C. There were 24 cases treated
      with minimally invasive locking plate internal fixation operation and 54 cases
      treated with open reduction with internal fixation operation. The patients were
      followed up with postoperative physical examinations and X ray examinations.
      Postoperative shoulder pain after 1 week and more than 6 months was assessed
      using the VAS score. Postoperative shoulder joint function with the use of
      Constant-Murley score and ASES score were evaluated after 3 months and more than
      6 months. The results were analyzed by SPSS 18.0. RESULTS: The follow-up time was
      6 to 85 months, with the mean time of 33.8 months. According to the rank sum
      test: there were significant differences in operation time (P=0.002),
      postoperative hospital day (P=0.001), the satisfaction of patients (P=0.029),
      postoperative shoulder pain after 1 week (P=0.024), postoperative Constant-Murley
      score after 3 months (P=0.012) and postoperative ASES score after 3 months
      (P=0.001) between minimally invasive group and non-minimally invasive group.
      There weren't significant differences in clinical union time of bone (P=0.446),
      postoperative shoulder pain after more than 6 months (P=0.894), postoperative
      Constant-Murley score after more than 6 months (P=0.122) and postoperative ASES
      score after more than 6 months (P=0.351) between minimally invasive group and non
      minimally invasive group. There were no breakage of the internal fixation and
      humeral head osteonecrosis. Minimally invasive group had 2 cases with internal
      fixation loosening (8.3%) and 1 case with complete limitation of abduction
      (4.2%). Non-minimally invasive group had 1 case with tracture nonunion (1.9%), 1
      case with internal fixation loosening (1.9%) and 1 case with complete limitation
      of abduction (1.9%). CONCLUSION: The operation method of proximal humerus
      fractures is an important factor affecting the recovery of shoulder joint
      function. Minimally invasive locking plate internal fixation operation in early
      stage (1 week) of pain control, early (3 months) functional recovery, operation
      time, postoperative hospital day and patient satisfaction are better than those
      of traditional operation.

PMID- 24136265
TI  - [Assisting plate with reamed intramedullary nailing for segmental fractures of
      proximal-middle tibia].
AB  - OBJECTIVE: To evaluate the efficacy and safety of combining reduction plating
      with reamed intramedullary nailing for segmental fractures of proximal-middle
      tibia. METHODS: From June 2007 to October 2011, 31 patients with segmental
      fractures of proximal-middle tibia were admitted. There were 18 males and 13
      females, with an average age of 45.2 years (range: 23-77 years), of whom, 9 were
      Gustilo I type open fractures and 22 were close fractures. All the patients were
      treated with assisting plate combined with reamed intramedullary nailing. The
      operation was performed averagely 35 h (range: 16-72 h) after injury. During the
      post-operation follow-up radiographic evaluation, the range of knee joint, and
      Johner-Wruhs scores were measured. RESULTS: All the patients were followed-up for
      18.5 months (range: 17-24 months). No wound infection or osteofascial compartment
      syndrome happened. All the fractures healed after 5.1 months (range: 4-6 months).
      The proximal and distal fracture sites healed simultaneously. No malunion was
      found. In the last follow-up, the mean range of knee joint was 9 degrees -0
      degrees -127 degrees , and according to Johner-Wruhs scores, 19 were excellent,
      10 good, and 2 fair. CONCLUSION: Assisting plate with reamed intramedullary
      nailing is a safe and effective alternative choice for segmental fractures of
      proximal-middle tibia, which can ease the difficulty of the procedure, improve
      the quantity of reduction and enhance the stability of the hardware.

PMID- 24136266
TI  - [Finite element analysis of lumbar fusion and Topping-off surgery].
AB  - OBJECTIVE: To evaluate the effect of Topping-off surgery on the adjacent segment
      of PLIF. METHODS: A finite element model of the human lumbar spine (L1-L5) was
      developed. The intact spinal model was validated by comparing it with previously
      reported models. Then, 2 models were analyzed and compared: (1) posterior lumbar
      interbody fusion (PLIF) at L4/5; (2) posterior lumbar interbody fusion at L4/5
      and implantation of the interspinous spacer (ISP) at L3/4 (Topping-off). Then 500
      N compressive loading plus 10 Nm moments simulating flexion, extension, lateral
      bending and axial rotation were imposed on both the L1 superior endplates. The
      ranges of motion, intradiscal pressures, facet stresses in L3/4, the stresses on
      spinous processes in L3 and L4 were investigated. All the measured data were
      analyzed by SPSS 21.0. RESULTS: The effect of the Topping-off on the adjacent
      segment appeared mainly in flexion-extension: the ranges of motion, intradiscal
      pressures (annulus and nucleus pulposus), both facet stresses were lower than
      that of the PLIF model, and the stresses on spinous processes in L3 and L4 were
      larger. Besides, the facet stresses on the left side in the left lateral bending
      were also lower than those of the PLIF model. CONCLUSION: Topping-off model is
      able to restrict the range of motion of the lumbar adjacent segment, decrease the
      intradiscal pressure and facet stresses, and has a potential effect of preventing
      adjacent segmental degeneration.

PMID- 24136267
TI  - [Minimal invasive internal fixation with U-shaped break-off pedicle screws for
      treatent of thoracolumbar fractures].
AB  - OBJECTIVE: To investigate the clinical outcome of minimal invasive internal
      fixation with U-shaped break-off pedicle screws through paraspinal muscle sparing
      approach to treat thoracolumbar fractures, and to discuss its advantages.
      METHODS: From August 2010 to June 2012, we had 40 thoracolumber fractures
      patients (27 males and 13 females). Their ages ranged from 22 to 60 years. Of the
      40 cases, 4 were T11 fractures, 13 T12 fractures ,17 L1 fractures,6 L2 fractures.
      According to Denis classification,all of them were burst fractures, with
      vertebral canal compromise less than 1/3. According to AO classification they
      were type A or type B1 injuries. All the cases had no nerve injury. The patients
      were randomly divided into two groups. With Group A (20 cases) we took the method
      of minimal invasive internal fixation with U-shaped break-off pedicle screws to
      fix one level above and below the injured vertebra through the parespinal muscle
      sparing approach. With Group B (20 cases), we took the traditional posterior
      midline approach and open procedure. Then we compared the two groups by operation
      time, blood loss, drainage, Visual Analogue Scales and X-ray exposure. RESULTS:
      Minimal invasive group had obvious advatages in operation time, bleeding control
      and early pain relief of post-operation. The X-ray exposure and long-term follow
      up outcome were almost the same. CONCLUSION: Through paraspinal muscle sparing
      approach minimal invasive internal fixtation with U-shaped break-off pedicle
      screws to treat thoracolumber has more advantages than traditional procedure in
      blood control and quick recovery. The method needs no special instruments and
      don't increase X-ray exposure.

PMID- 24136268
TI  - [Analysis of sagittal parameters about senior thoracolumbar proximal junctional
      kyphosis after lumbar long segment fusion].
AB  - OBJECTIVE: To explore the radiographic risk factors of senior thoracolumbar
      proximal junctional kyphosis (PJK) after lumbar long segment fusion. METHODS:
      From January 2009 to December 2011, the PJK group enrolled 9 patients who
      satisfied the following criteria: being older than 60 years, having lumbar fusion
      operation no less than 4 levels, upper instrumented vertebrae being L1 or L2,
      emerging PJK in 2-year follow-up, and the control group enrolled 10 matched
      patients without PJK. Their sagittal parameters including sagittal vertical axis,
      thoracic kyphosis, lumbar lordosis, upper instrumented vertebral angle, pelvic
      incidence, sacral slope, pelvic tilt, lumbo-pelvic lordosis on full length spine
      lateral film were measured, the oswestry disability index (ODI ) scores of the
      two groups in the last follow up recorded, and the parameters and ODI scores of
      two groups compared. RESULTS: The phenomena of PJK emerged average 7.9 months
      post-operation. The patients' lumbar lordosis reduced and compensatory pelvic
      appeared backward obviously after PJK emerged. Compared with the control group,
      lumbar lordosis, pelvic radius-T12 (PR-T12), upper instrumented vertebral angle
      were small in the PJK group, suggesting more severe lumbar pelvic imbalance. The
      ODI scores of the PJK group and contral group were 40.6 +/- 15.9 and 21.5 +/-
      15.0 respectively, and the difference was significant. CONCLUSION: PJK after
      lumbar long segment fixation of elderly patients can aggravate the sagittal
      imbalance and reduce functional scores. The operator should pay great attention
      to restoring the lumbo-pelvic lordosis.

PMID- 24136269
TI  - [Analysis of the blood loss in perioperative period of femoral intertrochanteric
      fractures in old patients treated with different internal fixations].
AB  - OBJECTIVE: To analyze blood loss in perioperative period of femoral
      intertrochanteric fractures in old patients treated with Gamma interlocking
      intramedullary nail (Gamma3), proximal femoral nail antirotation (PFNA) and
      dynamic hip screw (DHS), and to comprehend the character of blood loss in
      perioperative period of femoral intertrochanteric fractures. METHODS: A
      retrospective analysis was made of the medical records of 408 old patients with
      femoral intertrochanteric fractures admitted to our hospital between January 1,
      2007 and to December 31, 2012. The estimated blood loss was calculated by Gross
      equation, according to the height, weight and changes of blood test pre- and post
      operation and the differences of blood loss among Gamma3 group, PFNA group and
      DHS group were compared. The statistical analysis was conducted using One-Way
      ANOVA analysis with SPSS 13.0. A P value less than 0.05 was considered
      statistically significant. RESULTS: In the Gamma3 group (96 cases, 39 males, 57
      females), the average operation time was (74.7 +/- 25.0) min, the mean obvious
      blood loss was (103.5 +/- 83.0) mL, the mean total blood loss was (831.9 +/-
      474.8) mL, and the mean hidden blood loss was (728.3 +/- 455.5) mL. In the PFNA
      group (84 cases,31 males, 53 females), the average operation time was (69.0 +/-
      27.1) min, the mean obvious blood loss was (91.5 +/- 111.4) mL, the mean total
      blood loss was (825.7 +/- 478.0) mL, and the mean hidden blood loss was (734.2 +/
      455.7) mL. In the DHS group (40 cases, 14 males, 26 females), the average
      operation time was (97.5 +/- 25.0) min, the mean obvious blood loss was (283.6 +/
      142.1) mL, the mean total blood loss was (695.7 +/- 502.4) mL, and the mean
      hidden blood loss was (412.1 +/- 457.6) mL. CONCLUSION: By comparing the three
      kinds of internal fixation methods we find that the Gamma3 and PFNA groups have a
      smaller size of incision, shorter time of operation and less intraoperative
      bleeding than the DHS group, but there is a considerable perioperative hidden
      blood loss. We should give enough attention to reducing the incidence of
      postoperative complications.

PMID- 24136270
TI  - [Impact of hip fracture on coagulation function in elderly patients].
AB  - OBJECTIVE: To investigate the impact of hip fracture on coagulation function in
      elderly patients. METHODS: In our study, 127 elderly patients with hip fracture
      were diagnosed and admitted to Peking University People's Hospital from January
      2011 to March 2012. Specimens of their venous blood were obtained before and
      after the surgery, and measured for fibrinogen (FIB) and D-dimer. Also, we
      analyzed their age, type of fracture, fracture time, and concomitant diseases.
      RESULTS: The FIB level of the patients (127 cases) before surgery was (3.91 +/-
      1.06) g/L, and 42.52% (54/127) patients' FIB was higher than normal. After the
      surgery, 28 patients underwent FIB test [(4.21 +/- 1.24) g/L], which was higher
      than the FIB value before surgery, but was not statistically significant. Before
      surgery, 15 patients underwent D-dimer test [(2 059.5 +/- 1 948.0) MUg/L]. After
      the surgery, 26 patients underwent D-dimer test [(2 574.9 +/- 1 702.4) MUg/L].The
      two values were significantly higher than normal (P<0.05). The elevated value of
      FIB had no relationship with age, diabetes, cardiovascular or cerebrovascular
      diseases. Before surgery, 45.83% (22/48) of the intertrochanteric fracture
      patients had abnormal FIB, and 40.50% (32/79) of the patients with femoral neck
      fracture had abnormal FIB, but they were not statistically significant. Grouped
      according to the fracture time, when fracture time was longer than 96 h, the
      ratio of abnormal FIB was 26.7%, lower than those of other groups, and the
      difference was statistically significant (P<0.05). CONCLUSION: The hip fracture
      in elderly patients has a direct impact on coagulation system, and FIB and D
      dimer have significantly changed. According to the variation of FIB after
      fracture,we speculate that fracture surgery after 96 h may affect the coagulation
      system at the lowest level.

PMID- 24136271
TI  - [Surgical treatment for long bone giant cell tumor of extremity with pathologic
      fracture].
AB  - OBJECTIVE: To identify the clinical features of patients with giant cell tumors
      (GCT) of long bones in extremities presented with pathological fracture (PF), and
      discuss the surgical strategy with retrospective analysis and literature review.
      METHODS: We searched medical electronic records from January 1999 to December
      2011 in our hospital to identify patients with definite diagnosis of extremity
      GCT presented with PF. Clinical data including gender, tumor site, age, surgical
      treatment option, postoperative complication, limb function, local recurrence and
      pulmonary metastasis were collected and analyzed statistically. The t-test and
      chi-square test were used for continuous and dichotomous variables, respectively.
      RESULTS: Between 1999 and 2011 we treated 201 patients with GCT in extremities
      (long bone only: femur, tibia, fibula, humerus, ulna, and radius), 33 of whom
      presented with a PF. The gender ratio was 1.06 for a male predominance. The
      median age was 33 (15-62), and the most common site of pathologic fractures was
      distal femur (n=17), followed by proximal tibia (n=5), proximal femur (n=5),
      proximal humerus (n=4), and distal radius (n=2). Nine fractures were intra
      articular. The tumors were treated by extended curettage (n=11) or en bloc
      excision (n=22), and the fractures were reconstructed by endoprosthesis (n=20),
      autologous iliums graft combined with synthetic bone substitutes (n=7), acrylic
      cementing (n=3), autologous fibula graft (n=2), or allograft (n=1). Ten
      operations were followed by complications of any kind, where implant failure and
      recurrence were the commonest, and re-operation rate was 27.3%. The mean
      functional score according to the scoring system of the Musculoskeletal Tumor
      Society (MSTS) was 81% in patients who received endoprosthesis replacement and
      82% in other reconstruction options. CONCLUSION: Extended curettage and en bloc
      resection were all considered to be the effective treatment options for patients
      with extremity GCT presented with PF. However, local recurrence and implant
      related complication were the major concern for joint reservation and prosthetic
      replacement, respectively.

PMID- 24136272
TI  - [Surgical managements for bone metastases in tibia of 16 cases].
AB  - OBJECTIVE: To investigate the different surgical options for tibia metastatic
      disease and to evaluate the survival prognostic factors, postoperation function
      and complications. METHODS: A retrospective evaluation of 16 patients treated for
      tibia metastatic disease between Jan. 2000 and Feb. 2013 was conducted at our
      center. The underlying histology of the lesions showed metastatic lung carcinoma
      (five),breast carcinoma (three), bladder carcinoma (two), unknown (two), renal
      cell carcinoma, colon carcinoma, hepatic cellular cancer and lymphoma (one each).
      The locations of these lesions were proximal in 11 patients (with one patient
      having two synchronous lesions in the proximal metaphysis on both sides),
      diaphyseal in 4 patients, and distal metaphyseal in two patients. One patient
      presented with a pathologic fracture,and the risk of impending pathologic
      fracture of the remainders was evaluated by Mirels scoring system. Of all the 16
      patients, 15 were treated surgically (with 16 operations performed). Six of them
      were reconstructed with proximal tibial replacement, 9 underwent curettage and
      cementation (with or without inner-fixations), and 1 patient had lower third calf
      amputation. We employed VAS scoring system to evaluate the pain intensity of the
      lesions before and after operation.The post-operation function was assessed by
      MSTS scoring system. The survival rate was described by Kaplan-Meier survival
      curve. RESULTS: Fourteen of all the patients were followed-up and enrolled in the
      research. The median postoperative survival was 7 months (1-72 months).The mean
      half year survival rate and 2-year survival rate were 57.14% and 8.9%
      respectively.The mean Mirels score was 9.8 +/- 1.0. The mean VAS score before the
      operation was 7.62 +/- 1.03, which turned out to be 1.36 +/- 0.86 after the
      operation. The mean MSTS score for the endoprosthesis and curettage was 21.0 +/-
      0.63 and 23.1 +/- 1.25 respectively. CONCLUSION: The mobidity of tibia metastatic
      diseases is very low.Surgical intervention, combined with the application of
      bisphosphonate and postoperative radiotherapy, is absolutely necessary for the
      treatment of tibial metastatic disease, contributing to an improved quality of
      life and limb function.

PMID- 24136273
TI  - [Surgical treatment strategy of the floating shoulder injury].
AB  - OBJECTIVE: To discuss the clinical characteristics and the surgical treatment
      strategy of the floating shoulder injury. METHODS: 26 cases with the floating
      shoulder injury between January 2006 and January 2012 were retrospectively
      evaluated. There were 15 males and 11 females with an average age of 35.2 (22-60)
      years. According to Wong's classification of floating shoulder injury: type IA, 3
      cases; type IB, 9 cases; type II, 4 cases; type IIIA, 6 cases; type IIIB, 4
      cases. All the 26 cases had accepted the surgical treatment. We observed the
      postoperative fracture reduction, damage repair, fracture healing and internal
      fixation through the X-ray films. We also evaluated the shoulder function
      regularly according to the Constant scores and Herscovici evaluation criteria.
      RESULTS: The 26 cases were followed up for an average of 16.8 (12-24) months.All
      the fractures healed for a mean time of 2.4 months, the mean Constant score was
      89.4 (60-100). The effect of Herscovici evaluation criteria: excellent, 15 cases;
      good, 8 cases;fair, 3 cases;the excellent rate 88.5%. CONCLUSION: Open reduction
      and internal fixation is an effective method for the treatment of floating
      shoulder injury, but we should select the reset sequence and fixation methods
      according to the type of fracture and degree of displacement.

PMID- 24136274
TI  - [Diagnostic values of heart rate variability on unexplained syncope in children].
AB  - OBJECTIVE: To investigate the diagnostic values of heart rate varibility (HRV) on
      unexplained syncope (UPS) in children. METHODS: Forty-nine children with
      unexplained syncope underwent head-up tilt test (HUT) and Holter monitering, then
      the differences were analyzed between HUT positive children and HUT negative
      children. The receiver operating characteristic (ROC) curve was used to explore
      the diagnostic values of HRV. RESULTS: Of the 49 patients, 32 (65.3%) were HUT
      positive. The diagnostic positive rate of HUT was 65.3%. The SDNNi, rMSSD, TP,
      ULF, VLF, LF and HF in the HUT positive group were significantly higher than
      those in the HUT negative group (P<0.05), respectively. There were no significant
      differences in SDNN, pNN50 and triangular index between the patients with
      different HUT outcomes (P>0.05). The ROC curve on the predictive values of SDNNi,
      rMSSD, TP, ULF, VLF, LF and HF showed that ULF, LF, and HF (12 947.00, 9 462.50,
      and 9 509.00) as cutting values produced both high sensitivity (75.0%, 68.8%, and
      68.8%) and specificity (64.7%, 64.7%, and 64.7%) to predict the diagnostic values
      of HUT for diagnosing unexplained syncope. CONCLUSION: ULF, LF and HF can be
      considered as indicators for diagnosing neurally-mediated syncope in children.
      ULF, LF, and HF (12 947.00, 9 462.50, and 9 509.00) taken as cutting values may
      produce both high sensitivity and specificity.

PMID- 24136275
TI  - [Quantitative ultrasound scans of the calcaneus: a useful tool for screening
      osteoporosis in patients with connective tissue disease].
AB  - OBJECTIVE: To evaluate the ability of calcaneus quantitative ultrasound (QUS) to
      diagnose osteoporosis in connective tissue disease (CTD) patients. METHODS: In
      the study, 126 female patients with established CTD underwent dual-energy X-ray
      absorptiometry (DXA) of the lumber and right hip and QUS of the right heel at the
      same time. Sensitivity, specificity, as well as positive and negative predictive
      values were calculated to determine the correlation between cases of osteoporosis
      detected by the QUS heel scan and by DXA. RESULTS: The mean age of the 126
      patients was (43.4 +/- 19.8) years (ranging from 30.0 to 80.0 years). Based on
      their DXA data, 36 (28.6%) patients had normal bone mineral density (BMD, T score
      >= -1.0), 90 (71.4%) patients had abnormal BMD. In abnormal BMD patients, 45
      (35.7%) had osteopenia (-2.5 < T score<-1.0), and 42 (33.3%) were osteoporotic (T
      score <= -2.5), while 3 (2.4%) patients had fragile fracture. Broadband
      ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were
      all significantly different between osteopenia and the normal group when scanning
      with QUS. QUS T score was positively correlated with DXA T score, both at lumber
      and right hip respectively (r=0.491, 0.648, P<0.01). After correction by age and
      BMI, QUS T score remained positively correlated with DXA T score by partial
      correlation analysis (Pearson partial vertebral r=0.430, P=0.006; right hip
      r=0.593, P<0.001). The area under the ROC curve for diagnosis of lumber and hip
      osteoporosis were 0.836 (95%CI: 0.695, 0.977) and 0.647 (95%CI: 0.579, 0.957)
      separately. The sensitivity and specificity for identifying osteoporosis in
      lumber were 70% and 83.3% respectively when the T score threshold of QUS was
      defined as -1.5; however, the sensitivity and the specificity for identifying
      osteoporosis at right hip were 72.7% and 88.9% when T score threshold of QUS was
      defined as -1.85. The best SI threshold was defined as 76 for identifying
      osteoporosis, with sensitivity being 0.800 and specificity 0.741. CONCLUSION: Our
      study confirmed that QUS measurements performed at calcaneus with quantitative
      ultrasound bone analysis were capable of screening osteoporosis defined by axial
      BMD using DXA in female CTD patients.

PMID- 24136276
TI  - [Effects of ethane dimethane sulfonate on fetal Leydig cells in neonatal rats].
AB  - OBJECTIVE: To investigate the effects of ethane dimethane sulfonate (EDS) on
      fetal Leydig cells (FLCs) in neonatal rats. METHODS: In the study, 40 male
      neonatal SD rats were divided into control group and experimental groups. The
      rats in the experimental groups aged 3 days (PND3) were intraperitoneally
      injected with one single EDS (75, 100 and 125 mg/kg). The samples were collected
      on PND7. The body and testes was weighed, and the serum level of testosterone was
      detected. One testis was for histological analysis (3beta-hydroxysteroid
      dehydrogenase stainining), and the other was frozen in refrigerator for molecular
      determination (RT-PCR, Western blot). RESULTS: Compared with the control group,
      on day 4 after EDS treatment, significant decrease of serum testosterone was
      observed in the 75, 100 and 125 mg/kg experimental groups [(0.542 +/- 0.117)
      MUg/L, (0.124 +/- 0.021) MUg/L, (0.113 +/- 0.015) MUg/L, vs. (0.834 +/- 0.172)
      MUg/L, P<0.05]. Meanwhile, fetal Leydig cells in clusters disappeared with a
      lower expression level of Hsd3b1 and Cyp17a1 after EDS treatment in the testes of
      neonatal male rats in EDS (100 mg/kg)-treatment group (P<0.001). CONCLUSION:
      Ethane dimethane sulfonate can specifically deplete the fetal Leydig cells in
      testes of neonatal rats. Thus we could establish the FLCs' depletion model to
      know more about these testicular interstitial cells.

PMID- 24136277
TI  - [Urachal carcinoma: experience of a clinical center within 30 years].
AB  - OBJECTIVE: To summarize more than thirty years of experience with urachal
      carcinoma and to discuss the clinical features of urachal carcinoma. METHODS: The
      clinical data of 22 patients with urachal carcinoma, 18 males and 4 females,
      their median age at diagnosis was 52 years (range: 31-77 years), were analyzed
      retrospectively. RESULTS: Twenty-one cases were urachal adenocarcinoma, and 1 was
      small cell carcinoma. The first common symptom was gross hematuria in the urachal
      carcinoma patients (20/22, 90.9%), and CT showed calcification in 18.75% of them
      (3/16). The cystoscopic finding was a mass seen at the dome of the bladder or
      anterior wall in all. Twenty cases were followed up (90.9%), with the median
      follow-up 28 months (range: 3-184 months). The overall 5-year cancer-specific
      survival rate was 49.5%. It was significantly different in survival between T2
      and T3 or more in the urachal carcinoma patients by survival analysis (P=0.026).
      CONCLUSION: The results indicate that the most important predictor of prognosis
      is tumor stage, and it is critical for diagnosis of urachal carcinoma by CT scan
      and cystoscopy. Extended partial cystectomy is the main surgery of patients with
      urachal carcinoma. Active multimodal treatments may improve the survival of
      patients with recurrent and metastatic disease.

PMID- 24136278
TI  - [Association factors analysis of diarrhea in patients receiving kidney
      transplantation].
AB  - OBJECTIVE: To investigate the factors in association with colorectal disorders in
      adult renal transplant recipients. METHODS: A retrospective cohort study was
      carried out with clinical, microbiological and management data regarding diarrhea
      in 513 renal transplant recipients from Jan. 2007 to Dec. 2012. RESULTS: Of the
      513 patients, 118(23.00%) with no history of ulcerative colitis, were found to
      have diarrhea after kidney transplantation. In the 118 patients, diarrhea was
      probably caused by administration of immunosuppressive agents in 65 cases
      (55.08%), in 30 cases (25.42%) diarrhea was antibiotics associated, and in 23
      cases (19.49%) it was due to infections, including bacterial, fungal and viral
      infections. Diarrhea occurred soon after transplantation in most cases. Of the
      118 patients, the symptom of diarrhea occurred in the first 1 month in 84 cases
      (71.19%), and in the next 5 months in 16 cases (13.56%), and the other 18 cases
      (15.05%) occurred after 180 days after transplantation. Of the 118 patients, 84
      cases (71.19%) were relieved or cured after proper diets, the symptomatic therapy
      or the adjust meat of the doses of immunosuppressive agents: 18 cases (15.25%)
      needed to use or adjust the antibiotics , 16 cases (13.56%) had to stop
      mycophenolate mofetil and convert to other drugs. CONCLUSION: Immunosuppressive
      agents, antibiotics and infection are the common causes of diarrhea after kidney
      transplantation. The outcome is good with appropriate conservative management.

PMID- 24136279
TI  - [A novel TaqMan(r) MGB probe for specifically detecting Streptococcus mutans].
AB  - OBJECTIVE: To design a new TaqMan(r) MGB probe for improving the specificity of
      Streptococcus mutans's detection. METHODS: We extracted six DNA samples from
      different streptococcal strains for PCR reaction. Conventional nested PCR and
      TaqMan(r) MGB real-time PCR were applied independently. The first round of nested
      PCR was carried out with the bacterial universal primers, while a second PCR was
      conducted by using primers specific for the 16S rRNA gene of Streptococcus
      mutans. The TaqMan(r) MGB probe for Streptococcus mutans was designed from
      sequence analyses, and the primers were the same as nested PCR. Streptococcus
      mutans DNA with 2.5 mg/L was sequentially diluted at 5-fold intervals to 0.16
      MUg/L. Standard DNA samples were used to generate standard curves by TaqMan(r)
      MGB real-time PCR. RESULTS: In the nested PCR, the primers specific for
      Streptococcus mutans also detected Streptococcus gordonii with visible band of
      282 bp, giving false-positive results. In the TaqMan(r) MGB real-time PCR
      reaction, only Streptococcus mutans was detected. The detection limitation of
      TaqMan(r) MGB real-time PCR for Streptococcus mutans 16S rRNA gene was 20 MUg/L.
      CONCLUSION: We designed a new TaqMan(r) MGB probe, and successfully set up a PCR
      based method for detecting oral Streptococcus mutans. TaqMan(r) MGB real-time PCR
      is a both specific and sensitive bacterial detection method.

PMID- 24136280
TI  - [Effects of platelet-rich fibrin on canine dental pulp cells in vitro].
AB  - OBJECTIVE: To investigate the effect of platelet-rich fibrin (PRF) on the
      proliferation and chemotaxis capacity of autogenous canine dental pulp cells
      (cDPCs), and to evaluate the use of PRF as a pulp capping material in vital pulp
      therapy. METHODS: cDPCs were isolated and cultured from permanent anterior teeth
      of Beagle dogs by enzymatic methods. PRF was attained by Choukroun's protocols
      and the exudates of PRF were collected at the time point of the 7th day. Cell
      counting kit-8 (CCK-8) was applied to analyze cell proliferation. The medium of
      the control group was minimum essential medium alpha medium (alpha-MEM)
      containing 2% (volume fraction) fetal bovine serum (FBS). The experiment group
      was the exudates of PRF containing 2% FBS, and was divided into 5 groups (20%,
      40%, 60%, 80%, 100%) by the volume fraction of the exudates of PRF. The 5 groups
      were named as PRF1, PRF2, PRF3, PRF4 and PRF5 respectively. Transwell model was
      used to evaluate cell chemotaxis capacity. The exudates of PRF which was most
      effectively in promoting cDPCs proliferation was added in the lower chamber of
      the experimental group; The positive control group was alpha-MEM containing 30%
      FBS and the negative control group was fresh alpha-MEM; The upper chamber of each
      group was added with 1 * 105 cells. RESULTS: The optical density of group PRF2
      (1.45 +/- 0.06) was significantly higher than that of the control group(1.21 +/-
      0.11, P<0.001). The optical density of groups PRF1, PRF3, PRF4, and PRF5 were
      1.20 +/- 0.02, 1.28 +/- 0.04, 1.19 +/- 0.02, 1.22 +/- 0.02, respectively, and
      there was no significant difference between these groups and the control group
      (PRF1: P=0.902; PRF3: P=0.084; PRF4: P=0.726; PRF5: P=0.779). Therefore, the
      volume fraction which was most effective in promoting cell proliferation was 40%.
      At these concentrations the number of migrated cells was higher in PRF
      group(55.89 +/- 18.42) than in the negative group(6.52 +/- 1.97, P<0.001), but
      there was no significant difference between PRF group and the positive
      group(59.25 +/- 29.17, P=0.970). CONCLUSION: PRF was a biocompatible material
      with cDPCs. Appropriate concentration of the exudates of PRF accelerated the
      proliferation and migration of cDPCs, which contributes to pulp repair in vital
      pulp therapy.

PMID- 24136281
TI  - [Application of near infrared spectroscopy in study of occlusal splints and
      resistance of masticatory muscles to fatigue pain].
AB  - OBJECTIVE: To analyze the influence of occlusal splint on resistance capability
      of masticatory muscles to fatigue. METHODS: In the study, 25 young male
      volunteers were randomly divided to 5 groups according to different splint
      placements: (1) no splint, (2) 1.5 mm thick soft splint, (3) 2 mm thick resin
      stability splint, (4) 4 mm thick resin stability splint, (5) buccolingual mock
      splint. Near infrared spectroscopy (NIRS) was used to measure blood oxygen
      content in human masticatory muscles during constant strong biting before and
      after the splint placement at seven time points: before, baseline after, 1 week
      after, and 2 weeks after splint placement, and immediately after, 1 week after,
      and 5 weeks after removing of splints. The strength of the biting force was
      maintained constantly at 30% level of the maximum biting force of each subject by
      biofeedback to the displayed value of an electro-myographic monitor. The time
      points of muscular fatigue and pain that appeared were recorded and the
      correlation between the subjective feeling and the NIRS measurement result was
      analyzed. RESULTS: The NIRS measurement curve had a point of inflection that had
      no significant difference with the time point of the muscle pain that appeared.
      Two weeks after placement of soft splint, the time point of the muscular fatigue
      and pain that appeared were 2.75 s and 8.00 s delayed respectively compared with
      that before placement of splint (P<0.01) while they were earlier in the groups of
      hard splints and there was no significant difference (P>0.05) in the group of
      mock splint. CONCLUSION: The metabolic status of human masticatory muscles could
      be monitored in real time by using NIRS; soft splint delayed the appearing of
      muscle fatigue and muscle pain after two weeks of placement.

PMID- 24136282
TI  - [Effect of early-loaded small diameter implants retained mandibular overdentures
      on masticatory performance].
AB  - OBJECTIVE: To evaluate the clinical effect and masticatory efficiency of two
      early loaded Small Diameter Implants (SDI) retained mandibular overdentures.
      METHODS: Eight mandibular edentulous patients received two SDIs insertion between
      mental foramina. The mandibular overdentures were connected with implants for
      early loading in the period of 2-4 weeks following implant insertion. The data of
      visual analogue scale (VAS) of denture satisfaction and masticatory ability were
      collected at baseline, two weeks, three months and six months following
      overdenture loading. Masticatory efficiency was evaluated before surgery and six
      months after overdenture loading. RESULTS: Within the period of six months
      following overdenture loading, all the 16 implants remained stable. Compared with
      the baseline, the VAS data of denture satisfaction,stability, masticatory and
      poltophagy ability two weeks, three months and six months after overdenture
      loading were significantly improved with 30 degree (P<0.01), especially the
      masticatory and poltophagy ability of hard and crisp food. The value of
      masticatory efficiency improved considerably six months after overdenture loading
      (P<0.01). CONCLUSION: Mandibular overdentures retained by two SDIs can
      significantly improve patients' denture satisfaction and masticatory efficiency,
      and provide more rational diet.

PMID- 24136283
TI  - [Evaluation of short-term clinical therapeutic efficiency of computer aided
      design and manufacturing titanium-ceramic-fixed partial dentures for implant
      supported restoration in posterior region].
AB  - OBJECTIVE: To evaluate the clinical results of computer aided design and computer
      aided manufacturing (CAD/CAM) titanium-ceramic-fixed partial dentures for implant
      supported restoration in posterior region. METHODS: In the study, 90 patients (47
      males, 43 females, and the mean age of 48.7 years ranging from 30-62 years) with
      posterior tooth missing underwent implant-supported porcelain fuse mental
      prostheses with CAD/CAM titanium-base. A total of 135 prostheses (159 prosthetic
      units) were fabricated, and 152 implants were placed. The evaluators examined the
      integrity of restoration, gingival health, color match and marginal adaptation.
      The mean follow-up time was 51.9 months (24-80 months). RESULTS: No implant was
      lost during the loading time. All the patients were satisfied at the end of their
      treatment. The chipping rate of porcelain fuse mental prostheses with CAD/CAM
      titanium-base was 13.2%(21/159 prosthetic units), No fracture of titanium-base
      was observed, and 7.4% (10/135) prostheses were found loosening. The authors
      rated 97.8% (132/135) prosthesis as good or better in regard to color match, 100%
      (152/152) implants had excellent marginal adaptation. CONCLUSION: The implant
      supported titanium-based porcelain fuse mental prostheses with CAD/CAM show good
      marginal integrity and shade stability, with a clinically acceptable chipping
      rate, and these restorations can achieve success in the case of posterior tooth
      missing. Further study is needed to determine the long-term results.

PMID- 24136284
TI  - [Generation and characterization of peripheral nerve animal model of pure
      motor/sensory nerve fibers].
AB  - OBJECTIVE: To generate peripheral nerve animal model of pure motor nerve
      fibers/pure sensory nerve fibers, and identify them. METHODS: The SPF SD rats
      were adopted in this study, and divided into 3 groups. In group A, we ablated L2
      L4 ventral roots (VRs) to generate peripheral nerve animal model of pure sensory
      fibers. In group B, we ablated L2-L4 dorsal root ganglions (DRGs) to generate
      peripheral nerve animal model of pure motor fibers. Two time end-points were set
      as 2 weeks and 4 weeks. Neuron cells in lumbar spinal cords were detected by
      immunohistochemical staining with antibody of neuronal nuclei (NeuN). Motor
      neuron cells in lumbar spinal cords of pure motor fiber animal models and sensory
      neuron cells in lumbar spinal cords of pure sensory fiber animal models were
      counted respectively, and then compared to that of normal animals. Femoral nerves
      distal to the furcation were stained in osmium tetroxide, and then myelinated
      nerve fibers in the muscle branch and cutaneous branch of femoral nerve were
      counted respectively. RESULTS: The mean numbers of sensory neuron cells and motor
      neuron cells in normal lumbar spinal cords were 62.57 +/- 1.02 and 29.73 +/- 3.03
      per 10 * 20 visual field respectively. For different end-points, the mean numbers
      of sensory neuron cells after ablating vental foots were 62.12 +/- 1.77 (2
      weeks), 62.15 +/- 1.32 (4 weeks) per 10 * 20 visual field respectively; the mean
      numbers of motor neuron cells after ablating DRGs were 30.12 +/- 0.44 (2 weeks),
      30.00 +/- 1.87 (4 weeks) per 10 * 20 visual field respectively. In group A, motor
      axons in muscle branch were degenerated as the sensory axons in muscle branch and
      cutaneous branch were not changed. The senory axons in femoral nerve for the two
      end-points were 1 558.17 +/- 50.14 (2 weeks) and 1 544.00 +/- 47.42 (4 weeks). In
      group B, sensory axons in muscle branch were degenerated as the motor axons were
      reserved. The motor axons in muscle branch for the two end-points were 387.67 +/-
      48.50 (2 weeks) and 393.50 +/- 27.86 (4 weeks). There was no statistically
      significant difference in these mean numbers for the two end-points. The
      degenerating axons and myelin sheath had not been totally eliminated by the
      endpoint of 2 weeks. CONCLUSION: Peripheral nerve animal model of pure motor
      fibers can be generated by ablating L2-L4 DRGs; peripheral nerve animal model of
      pure sensory fibers can be generated by ablating L2-L4 ventral roots. The
      degenerating axons and myelin sheath have been totally eliminated by the end
      point of 4 weeks. Ablating the ventral roots does not influence the survival of
      sensory neuron cells; and ablating the DRGs does not influence the survival of
      motor neuron cells.

PMID- 24136285
TI  - [Treatment of comminuted clavicle shaft fractures with provisional intra
      medullary K-wire fixation and bridging plate internal fixation].
AB  - OBJECTIVE: To discuss the operation effect of comminuted clavicle shaft fractures
      with provisional intramedullary K-wire fixation and bridging plate internal
      fixation. METHODS: From Mar. 2008 to Jul. 2012, 22 cases of comminuted clavicle
      shaft fractures was treated with open reduction, and provisional intramedullary K
      wire fixation and bridging plate internal fixation. The fracture healing was
      investigated through X-rays. The 22 cases were followed up to evaluate the
      function of the affected shoulder with Constant score. RESULTS: Through the
      follow-up for average 15 months, all the fractures healed and the average healed
      time was 14.6 weeks. The average Constant score of the affected shoulder was
      95.3. There were 13 excellent cases, 7 good cases, and 2 fair cases. The fineness
      rate was 90.9% (20/22). Soft tissue problem resulting from plate tilting occurred
      in 2 cases. At last, they accepted second operation to remove the implant.
      CONCLUSION: Applying provisional intramedullary K-wire fixation and bridging
      plate internal fixation in comminuted clavicle shaft fractures, makes procedure
      simple, improves healing rate and decreases the complications.

PMID- 24136286
TI  - [Anesthesia management of laparoscopic radical cystectomy and orthotopic bladder
      surgery with a robotic-assisted surgical system].
AB  - OBJECTIVE: To summarize anesthesia management of laparoscopic radical cystectomy
      and orthotopic bladder surgery with a robotic surgical system. METHODS: In the
      study of 10 cases of bladder cancer, the robot-assisted radical cystectomy+expand
      lymphadenectomy+orthotopic bladder surgery with 60 degrees of Trendelenburg
      surgical position, was inserted into the manipulator under the video system
      monitor positioning, to complete the removal of the diseased tissue dissection
      and orthotopic ileal neobladder intra-abdominal. The respiratory parameters,
      hemodynamic parameters, arterial blood gas analysis were monitored and the waking
      time, intake and output, and intraoperative concurrent recorded. RESULTS: All the
      patients were operated successfully. The intraoperative blood loss was (342.9 +/-
      303.4) mL; the peak airway pressure increased after trendelenburg and high
      pneumoperitoneum; the mean arterial pressure heart rate and central venous
      pressure increased compared with the endotracheal intubation 15 minutes after two
      cases of the disease popularity abdominal end-expiratory CO2 partial pressure
      more than 50 mmHg, and PaCO2 higher than 60 mmHg in the arterial blood gas. When
      the respiratory parameters were adjusted, the hyperventilation showed no
      improvement, and when the pressure was reduced to less than 15 mmHg, the
      pneumoperitoneum improved; when metabolic acidosis occured in 2 patients, sodium
      bicarbonate post-correction was given; during surgery, 2 patients potassium rose
      to more than 5.5 mmol/L, gluconate and insulin were given; 5 patients developed
      multiple subcutaneous emphysema, of whom 1 was confined to the chest and abdomen,
      and 1 showed significant sense of gripping the snow from face to feet, associated
      with hypercapnia and temperature drop; the wake time (withdrawal to the
      extubation time) was (94.2 +/- 35.6) min. CONCLUSION: Robot-assisted radical
      cystectomy + orthotopic bladder surgery is a newly-performed clinical surgery.
      Because of the huge machines, long time pneumoperitoneum and over-head-down, it
      is prone to acid-base balance and ion imbalance, thus increasing the difficulty
      and complexity to anesthesia management. It's necessary to further summarize the
      impact on the respiratory, hemodynamic, and nervous system.

PMID- 24136287
TI  - [Radix hedysari extract promotes peripheral nerve regeneration].
AB  - Treatment of peripheral nerve injury is a major challenge in clinical practice.
      With advances in molecular biology and development of microsurgical techniques
      and tissue engineering, peripheral nerve repair procedures have been greatly
      improved. In the last 10 decades, most treatments for peripheral nerve injury in
      animal models have achieved histological and functional recovery, the treatments
      in humans, however, produce insufficient recovery, especially for proximal nerve
      injury. Increasing attention has been paid to the Traditional Chinese Medicine
      (TCM) for promoting peripheral nerve regeneration, since these remedies often
      display effective clinical outcome, minor side effects and effectiveness for
      multiple targets. Although TCM has complex ingredients and the specific
      pharmacological mechanisms for their effectiveness are still unclear, an
      effective clinical outcome is welcomed by many clinicians. In the past 20 years,
      we have made a series of detailed studies including the toxicity tests,
      pharmacodynamic tests, pharmacological experiments etc, about a new traditional
      formula which mainly contains the Radix hedysari, Epimedium etc. RESULTS have
      shown that this formula is safe to be used in both animals and humans with no
      toxicity and adverse effect, and systemic administration of this formula could
      enhance the peripheral nerve regeneration. 

PMID- 24136289
TI  - Identification and comparative analysis of hepatitis C virus-host cell protein
      interactions.
AB  - Hepatitis C virus (HCV) alters the global behavior of the host cell to create an
      environment conducive to its own replication, but much remains unknown about how
      HCV proteins elicit these changes. Thus, a better understanding of the interface
      between the virus and host cell is required. Here we report the results of a
      large-scale yeast two-hybrid screen to identify protein-protein interactions
      between HCV genotype 2a (strain JFH1) and cellular factors. Our study identified
      112 unique interactions between 7 HCV and 94 human proteins, over 40% of which
      have been linked to HCV infection by other studies. These interactions develop a
      more complete picture of HCV infection, providing insight into HCV manipulation
      of pathways, such as lipid and cholesterol metabolism, that were previously
      linked to HCV infection and implicating novel targets within microtubule
      organizing centers, the complement system and cell cycle regulatory machinery. In
      an effort to understand the relationship between HCV and related viruses, we
      compared the HCV 2a interactome to those of other HCV genotypes and to the
      related dengue virus. Greater overlap was observed between HCV and dengue virus
      targets than between HCV genotypes, demonstrating the value of parallel screening
      approaches when comparing virus-host cell interactomes. Using siRNAs to inhibit
      expression of cellular proteins, we found that five of the ten shared targets
      tested (CUL7, PCM1, RILPL2, RNASET2, and TCF7L2) were required for replication of
      both HCV and dengue virus. These shared interactions provide insight into common
      features of the viral life cycles of the family Flaviviridae. 

PMID- 24136290
TI  - Can postoperative mean transprosthetic pressure gradient predict survival after
      aortic valve replacement?
AB  - BACKGROUND: In this study, we sought to determine the effect of the mean
      transprosthetic pressure gradient (TPG), measured at 6 weeks after aortic valve
      replacement (AVR) or AVR with coronary artery bypass grafting (CABG) on late all
      cause mortality. METHODS: Between January 1998 and March 2012, 2,276 patients
      (mean age 68 +/- 11 years) underwent TPG analysis at 6 weeks after AVR (n =
      1,318) or AVR with CABG (n = 958) at a single institution. Mean TPG was 11.6 +/-
      7.8 mmHg and median TPG 11 mmHg. Based on the TPG, the patients were split into
      three groups: patients with a low TPG (<10 mmHg), patients with a medium TPG (10
      19 mmHg) and patients with a high TPG (>= 20 mmHg). Cox proportional-hazard
      regression analysis was used to determine univariate predictors and multivariate
      independent predictors of late mortality. RESULTS: Overall survival for the
      entire group at 1, 3, 5, and 10 years was 97, 93, 87 and 67%, respectively. There
      was no significant difference in long-term survival between patients with a low,
      medium or high TPG (p = 0.258). Independent predictors of late mortality included
      age, diabetes, peripheral vascular disease, renal dysfunction, chronic
      obstructive pulmonary disease, a history of a cerebrovascular accident and
      cardiopulmonary bypass time. Prosthesis-patient mismatch (PPM), severe PPM and
      TPG measured at 6 weeks postoperatively were not significantly associated with
      late mortality. CONCLUSIONS: TPG measured at 6 weeks after AVR or AVR with CABG
      is not an independent predictor of all-cause late mortality and there is no
      significant difference in long-term survival between patients with a low, medium
      or high TPG.

PMID- 24136291
TI  - Short-term outcome of patients with ST-segment elevation myocardial infarction
      (STEMI) treated with an everolimus-eluting bioresorbable vascular scaffold.
AB  - OBJECTIVES: To evaluate safety and efficacy of the everolimus-eluting
      bioresorbable scaffold (BVS) in patients with ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: According to the current guidelines, drug-eluting
      stents are the treatment of choice in patients with STEMI. BVS represents a new
      technology capable to restore the native vessel vasomotion and potentially
      avoiding long-term limitations such as stent thrombosis. METHODS: From October
      2012 to May 2013, patients with evidence of STEMI eligible for BVS implantation
      were included in this study. Exclusion criteria were not defined. RESULTS: A
      total of 25 patients, respectively 31 lesions, were treated. Procedural success
      was achieved in 97%. Two major adverse cardiac events occurred during
      hospitalization and follow-up: one patient with cardiogenic shock at the index
      procedure subsequently died. One patient suffered from instable angina with need
      for interventional revascularization of a previously untreated vessel. One target
      vessel failure as a consequence of an intra-procedural dissection was seen.
      However, no target lesion failure was noted. During 132.7 +/- 68.7 days of follow
      up none of the patients died. CONCLUSION: Our findings suggest that implantation
      of BVS in STEMI patients is feasible in this small cohort of highly selected
      patients. Further evaluation in randomized-controlled trials is needed.

PMID- 24136292
TI  - Association of gamma-aminobutyric acid A receptor alpha2 gene (GABRA2) with
      alcohol use disorder.
AB  - Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in
      mammalian brain. GABA receptor are involved in a number of complex disorders,
      including substance abuse. No variants of the commonly studied GABA receptor
      genes that have been associated with substance dependence have been determined to
      be functional or pathogenic. To reconcile the conflicting associations with
      substance dependence traits, we performed a meta-analysis of variants in the
      GABAA receptor genes (GABRB2, GABRA6, GABRA1, and GABRG2 on chromosome 5q and
      GABRA2 on chromosome 4p12) using genotype data from 4739 cases of alcohol,
      opioid, or methamphetamine dependence and 4924 controls. Then, we combined the
      data from candidate gene association studies in the literature with two alcohol
      dependence (AD) samples, including 1691 cases and 1712 controls from the Study of
      Addiction: Genetics and Environment (SAGE), and 2644 cases and 494 controls from
      our own study. Using a Bonferroni-corrected threshold of 0.007, we found strong
      associations between GABRA2 and AD (P=9 * 10(-6) and odds ratio (OR) 95%
      confidence interval (CI)=1.27 (1.15, 1.4) for rs567926, P=4 * 10(-5) and OR=1.21
      (1.1, 1.32) for rs279858), and between GABRG2 and both dependence on alcohol and
      dependence on heroin (P=0.0005 and OR=1.22 (1.09, 1.37) for rs211014).
      Significant association was also observed between GABRA6 rs3219151 and AD. The
      GABRA2 rs279858 association was observed in the SAGE data sets with a combined P
      of 9 * 10(-6) (OR=1.17 (1.09, 1.26)). When all of these data sets, including our
      samples, were meta-analyzed, associations of both GABRA2 single-nucleotide
      polymorphisms remained (for rs567926, P=7 * 10(-5) (OR=1.18 (1.09, 1.29)) in all
      the studies, and P=8 * 10(-6) (OR=1.25 (1.13, 1.38)) in subjects of European
      ancestry and for rs279858, P=5 * 10(-6) (OR=1.18 (1.1, 1.26)) in subjects of
      European ancestry. Findings from this extensive meta-analysis of five GABAA
      receptor genes and substance abuse support their involvement (with the best
      evidence for GABRA2) in the pathogenesis of AD. Further replications with larger
      samples are warranted. 

PMID- 24136293
TI  - Sub-anesthetic ketamine modulates intrinsic BOLD connectivity within the
      hippocampal-prefrontal circuit in the rat.
AB  - Dysfunctional connectivity within the hippocampal-prefrontal circuit (HC-PFC) is
      associated with schizophrenia, major depression, and neurodegenerative disorders,
      and both the hippocampus and prefrontal cortex have dense populations of N-methyl
      D-aspartate (NMDA) receptors. Ketamine, a potent NMDA receptor antagonist, is of
      substantial current interest as a mechanistic model of glutamatergic dysfunction
      in animal and human studies, a psychotomimetic agent and a rapidly acting
      antidepressant. In this study, we sought to understand the modulatory effect of
      acute ketamine administration on functional connectivity in the HC-PFC system of
      the rat brain using resting-state fMRI. Sprague-Dawley rats in four parallel
      groups (N=9 per group) received either saline or one of three behaviorally
      relevant, sub-anesthetic doses of S-ketamine (5, 10, and 25 mg/kg, s.c.), and
      connectivity changes 15- and 30-min post-injection were studied. The strongest
      effects were dose- and exposure-dependent increases in functional connectivity
      within the prefrontal cortex and in anterior-posterior connections between the
      posterior hippocampus and retrosplenial cortex, and prefrontal regions. The
      increased prefrontal connectivity is consistent with ketamine-induced increases
      in HC-PFC electroencephalographic gamma band power, possibly reflecting a
      psychotomimetic aspect of ketamine's effect, and is contrary to the data from
      chronic schizophrenic patients suggesting that ketamine effect does not
      necessarily parallel the disease pattern but might rather reflect a
      hyperglutamatergic state. These findings may help to clarify the brain systems
      underlying different dose-dependent behavioral profiles of ketamine in the rat.

PMID- 24136295
TI  - Stroke and recurrent left atrial appendage thrombus in a patient with atrial
      fibrillation under old and new oral anticoagulants: a case report.

PMID- 24136294
TI  - The cell surface proteome of Entamoeba histolytica.
AB  - Surface molecules are of major importance for host-parasite interactions. During
      Entamoeba histolytica infections, these interactions are predicted to be of prime
      importance for tissue invasion, induction of colitis and liver abscess formation.
      To date, however, little is known about the molecules involved in these
      processes, with only about 20 proteins or protein families found exposed on the
      E. histolytica surface. We have therefore analyzed the complete surface proteome
      of E. histolytica. Using cell surface biotinylation and mass spectrometry, 693
      putative surface-associated proteins were identified. In silico analysis
      predicted that ~26% of these proteins are membrane-associated, as they contain
      transmembrane domains and/or signal sequences, as well as sites of
      palmitoylation, myristoylation, or prenylation. An additional 25% of the
      identified proteins likely represent nonclassical secreted proteins.
      Surprisingly, no membrane-association sites could be predicted for the remaining
      49% of the identified proteins. To verify surface localization, 23 proteins were
      randomly selected and analyzed by immunofluorescence microscopy. Of these 23
      proteins, 20 (87%) showed definite surface localization. These findings indicate
      that a far greater number of E. histolytica proteins than previously supposed are
      surface-associated, a phenomenon that may be based on the high membrane turnover
      of E. histolytica. 

PMID- 24136297
TI  - Competition watchdog sees sharp rise in inquiries from CCGs.

PMID- 24136296
TI  - Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune
      reconstitution inflammatory syndrome.
AB  - The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can
      complicate combined treatments for HIV-1 and TB. Little is known about tissue
      damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the
      extracellular matrix and consequently may play a role in such immunopathology.
      Here we investigated the involvement of MMPs in TB-IRIS. We determined MMP
      transcript abundance and secreted protein in Mycobacterium tuberculosis
      stimulated PBMCs from 22 TB-IRIS patients and 22 non-IRIS controls. We also
      measured MMP protein levels in corresponding serum and the effect of prednisone-
      which reduces the duration of symptoms in IRIS patients--or placebo treatment on
      MMP transcript and circulating MMP protein levels. PBMCs from TB-IRIS had
      increased MMP-1, -3, -7, and -10 transcript levels when compared with those of
      controls at either 6 or 24 h. Similarly, MMP-1, -3, -7, and -10 protein secretion
      in stimulated cultures was higher in TB-IRIS than in controls. Serum MMP-7
      concentration was elevated in TB-IRIS and 2 weeks of corticosteroid therapy
      decreased this level, although not significantly. TB-IRIS is associated with a
      distinct pattern of MMP gene and protein activation. Modulation of dysregulated
      MMP activity may represent a novel therapeutic approach to alleviate TB-IRIS in
      HIV-TB patients undergoing treatment.

PMID- 24136298
TI  - Systems pharmacology modeling: an approach to improving drug safety.
AB  - Advances in systems biology in conjunction with the expansion in knowledge of
      drug effects and diseases present an unprecedented opportunity to extend
      traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct
      systems pharmacology modeling. Many drugs that cause liver injury and myopathies
      have been studied extensively. Mitochondrion-centric systems pharmacology
      modeling is important since drug toxicity across a large number of
      pharmacological classes converges to mitochondrial injury and death. Approaches
      to systems pharmacology modeling of drug effects need to consider drug exposure,
      organelle and cellular phenotypes across all key cell types of human organs,
      organ-specific clinical biomarkers/phenotypes, gene-drug interaction and immune
      responses. Systems modeling approaches, that leverage the knowledge base
      constructed from curating a selected list of drugs across a wide range of
      pharmacological classes, will provide a critically needed blueprint for making
      informed decisions to reduce the rate of attrition for drugs in development and
      increase the number of drugs with an acceptable benefit/risk ratio.

PMID- 24136299
TI  - Update in electromyography.
AB  - PURPOSE OF REVIEW: It is easy to forget the contribution of electromyography
      (EMG) to the investigation of paediatric peripheral neuromuscular disease, and
      this review highlights its continued importance. RECENT FINDINGS: The discovery
      that Brown-Vialetto-van Leare disease, when associated with disorder of
      riboflavin metabolism, may be treatable has raised awareness of the importance of
      EMG for its early detection. Unexpected discovery of motor neuronopathy, which
      may be useful for the definition of the phenotype of several conditions, now has
      an added significance. The investigation of disorders of peripheral nerve cannot
      proceed without nerve conduction studies but particular interest has been shown
      in its role in the management of obstetric brachial plexus palsy, with
      investigation within 1 month now recommended. The key role of neurophysiology in
      identifying abnormalities of the neuromuscular junction, and therefore leading
      investigators to a diagnosis of myasthenia, is once again highlighted. EMG in
      muscle disease continues to have a role, particularly when identifying myotonia.
      SUMMARY: Paediatric EMG, while a daunting technical challenge to some
      practitioners, remains a valuable investigative tool for the specialists in
      paediatric neuromuscular disorders and will continue to deliver important
      diagnostic information, often as quickly and accurately as other more recent
      innovations.

PMID- 24136300
TI  - Immunological features of 22q11 deletion syndrome.
AB  - PURPOSE OF REVIEW: 22q11 deletion syndrome is the most common genetic
      abnormality. More patients are surviving cardiac surgery, and many do not have
      cardiac anomalies. Adult patients are now being described. It is important for
      paediatricians, and increasingly adult physicians, to be aware of the optimum
      management of these patients. RECENT FINDINGS: Three main immunological patterns
      are recognized, namely, athymic and incomplete 22q11 deletion syndrome and
      autoimmunity. Newborn screening for severe combined immunodeficiency detects
      athymic patients, although diagnosis may be complicated, and instructive cases
      are described. Incomplete 22q11 deletion syndrome is the most common
      presentation; new findings predict which patients are likely to experience
      significant infection. B lymphocyte deficiencies are often overlooked. Data
      regarding autoimmunity in adult patients is reported, as well as newly reported
      immunological findings. Finally, management guidelines are now published, and
      these are highlighted. SUMMARY: Newborn screening detects patients with athymic
      22q11 deletion syndrome, but significant illness may complicate the picture, and
      dual diagnoses can confound treatment. Treatment options for these patients are
      becoming clearer. Hypoparathyroidism is associated with more severe infection,
      and immunoglobulin abnormalities are more common than previously recognized.
      Adult patients are symptomatic and management guidelines will help general
      physicians in managing these patients.

PMID- 24136301
TI  - Loteprednol etabonate ophthalmic gel 0.5% following cataract surgery: integrated
      analysis of two clinical studies.
AB  - INTRODUCTION: We aimed to evaluate the safety and efficacy of loteprednol
      etabonate (LE) gel 0.5% compared with vehicle in the treatment of postoperative
      inflammation and pain following cataract surgery, using the integrated analysis
      of data from two identical, prospective, multicenter, randomized, double-masked,
      parallel-group, vehicle-controlled trials. METHODS: Patients with anterior
      chamber cell (ACC) inflammation >= grade 2 (6-15 cells) 1 day post-surgery were
      randomized to receive 1 or 2 drops of LE gel 0.5% or vehicle 4 times per day
      instilled in the study eye for 14 days. Primary outcome measures included the
      proportion of patients with complete resolution of ACC and grade 0 (no) pain on
      postoperative Day 8. Safety endpoints included adverse events (AEs), changes from
      baseline in intraocular pressure (IOP) and visual acuity (VA), biomicroscopy, and
      funduscopy findings. Gel comfort was graded by patients according to drop
      sensation. RESULTS: The intent-to-treat population included 813 patients (409 LE
      gel 0.5% and 404 vehicle). At postoperative Day 8, 30.8% and 15.1% of patients
      randomized to LE gel 0.5% or vehicle, respectively, had complete resolution of
      ACC, while 74.3% and 43.8% of patients, respectively, had grade 0 pain (P < 0.001
      for both). Tolerability assessments for ocular itching, photophobia, and tearing
      favored LE gel 0.5% compared with vehicle at different time points beginning at
      Day 3. Two patients in the LE gel 0.5% group and 1 patient in the vehicle group
      exhibited a transient treatment-emergent increase in IOP >= 10 mmHg. Treatment
      related AEs were generally mild to moderate and occurred less frequently with LE
      gel 0.5% than with vehicle. Reports of treatment-related blurred vision were rare
      (n = 2, vehicle). CONCLUSION: LE gel 0.5% was efficacious and well tolerated in
      the treatment of postoperative pain and inflammation following ocular surgery,
      with minimal risk of IOP elevation.

PMID- 24136302
TI  - Mechanistic insight into halide oxidation by non-heme iron complexes.
      Haloperoxidase versus halogenase activity.
AB  - This work presents the first detailed study on mechanistic aspects of halide
      oxidation by non-heme iron complexes. We show that while iron(III)-hydroperoxo
      complexes oxidise halides via oxygen atom transfer, the corresponding iron(IV)
      oxo complex reacts via electron transfer.

PMID- 24136303
TI  - Transcranial application of near-infrared low-level laser can modulate cortical
      excitability.
AB  - BACKGROUND AND OBJECTIVE: Near-infrared low-level laser (NIR-LLL) irradiation
      penetrates scalp and skull and can reach superficial layers of the cerebral
      cortex. It was shown to improve the outcome of acute stroke in both animal and
      human studies. In this study we evaluated whether transcranial laser stimulation
      (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as
      measured by transcranial magnetic stimulation (TMS). METHODS: TLS was applied for
      5 minutes over the representation of the right first dorsal interosseal muscle
      (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked
      potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at
      baseline and up to 30 minutes after the TLS. RESULTS: The average MEP size was
      significantly reduced during the first 20 minutes following the TLS. The pattern
      was present in 10 (71.5%) of the participants. The MEP size reduction correlated
      negatively with the motor threshold at rest. CONCLUSIONS: TLS with NIR-LLL
      induced transitory reduction of the excitability of the stimulated cortex. These
      findings give further insights into the mechanisms of TLS effects in the human
      cerebral cortex, paving the way for potential applications of TLS in treatment of
      stroke and in other clinical settings.

PMID- 24136304
TI  - Active middle ear implant after lateral petrosectomy and radiotherapy for ear
      cancer.
AB  - BACKGROUND: Tumor of the temporal bone is a rare disease with a very poor
      prognosis. Surgery and postoperative radiotherapy are usually the recommended
      treatments for squamous cell carcinoma (SCC) of the external and middle ear,
      which may cause conductive hearing loss. The purpose of this study was to
      evaluate the audiologic results and compliance of active middle ear implant
      (AMEI) and establish the feasibility of the procedure in a patient treated for
      middle ear cancer. METHODS: A 73-year-old patient treated with lateral
      petrosectomy, neck dissection, reconstruction/obliteration by pedicled pectoralis
      major myocutaneous flap, and postoperative full dose radiotherapy for external
      and middle ear SCC was selected for AMEI. Preoperative audiometric and speech
      audiometry tests were performed on both ears before and after the activation.
      MAIN OUTCOME MEASURES: Pure tone free field audiometry. Binaural free field
      speech audiogram. RESULTS: Aided pure tone free field audiometry AMEI results
      show an increase in air conduction. Speech audiogram showed better discrimination
      scores in AMEI-aided situations. No complications were observed. CONCLUSION: AMEI
      after surgery followed by radiotherapy for middle ear cancer is feasible.
      Acoustic results in obliterated ear are satisfactory.

PMID- 24136305
TI  - Timing discrepancies of early intervention hearing services in urban and rural
      cochlear implant recipients.
AB  - OBJECTIVE: The purpose of this study was to examine the timing of early
      intervention diagnostic and therapeutic services in cochlear implant recipients
      from rural and urban areas. STUDY DESIGN: Retrospective case series review.
      SETTING: Tertiary referral center. PATIENTS: Cochlear implant recipients from a
      single comprehensive hearing institute born with severe congenital sensorineural
      hearing loss were examined. Timing of diagnostic and therapeutic services was
      examined. INTERVENTION(S): Diagnosis, amplification, and eventual cochlear
      implantation for all patients in the study. MAIN OUTCOME MEASURE(S): Time points
      of definitive diagnosis, amplification, and cochlear implantation for children
      from urban and rural regions were examined. Correlation analysis of distance to
      testing center and timing of services was also assessed. RESULTS: Forty children
      born with congenital hearing loss were included in the study and were diagnosed
      at a median age of 13 weeks after birth. Children from rural regions obtained
      amplification at a median age of 47.7 weeks after birth, whereas urban children
      were amplified at 26 weeks after birth. Cochlear implantation was performed at a
      median age of 182 weeks after birth in those from rural areas and at 104 weeks
      after birth in urban-dwelling patients. A linear relationship was identified
      between distance to the implant center and timing of hearing aid amplification (r
      = 0.5, p = 0.033) and cochlear implantation (r = 0.5, p = 0.016). CONCLUSION:
      Children residing outside of metro areas may be at higher risk of delayed
      rehabilitative services and cochlear implantation than those residing in urban
      areas that may be closer to tertiary care centers.

PMID- 24136306
TI  - Stability of audiometric measures and challenges in long-term management of the
      elderly cochlear implant patient.
AB  - OBJECTIVE: To determine the long-term audiometric stability and the types and
      frequency of management challenges encountered when working with elderly cochlear
      implant users. STUDY DESIGN: Retrospective chart review. SETTING: University
      hospital. PATIENTS: The final sample is 23 cochlear implantees over the age of
      60, followed an average of 8.4 years. INTERVENTION: Rehabilitative (cochlear
      implantation for clinical purposes, audiologic management). MAIN CLINICAL OUTCOME
      MEASURES: Warble tone thresholds, spondee thresholds, speech recognition scores,
      and frequency counts of management problems. RESULTS: Warble tone thresholds were
      stable over the study period. Speech recognition performance was not
      significantly changed statistically over the study period, but examination of
      individual results showed that 26% improved in performance, 17% participants
      decreased, and 17% remained the same. Thirteen percent of the sample had
      noteworthy thinning of the flap, including one individual whose flap deteriorated
      and required explantation.Management challenges relating to failing health,
      broken and lost equipment, thinning of the skin flap, critical judgment and
      emotional difficulties during programming sessions, and the need for repeated
      instructions on device use were noted with varying frequencies. CONCLUSION:
      Cochlear implantation is beneficial for elderly patients with severe-profound
      sensorineural hearing loss as demonstrated by long-term stability of function,
      with the caveat that some individuals may experience significant decreases in
      speech recognition over time. However, unique management challenges resulting
      from age-related cognitive decline, health problems, and/or reduced dexterity may
      present themselves. Audiologists must keep these issues in mind during
      preoperative counseling and when structuring postoperative follow-up sessions.

PMID- 24136307
TI  - Unilateral auditory performance before and after bilateral sequential cochlear
      implantation.
AB  - OBJECTIVE: The relationship between unilateral preimplantation and
      postimplantation auditory performance in patients undergoing sequential cochlear
      implantation (SCI) has not been clearly defined. A greater understanding of this
      relationship could affect preoperative counseling to patients regarding choice of
      initial side to implant. STUDY DESIGN: Retrospective case series. SETTING:
      Tertiary otologic practice. PATIENTS: Adult/pediatric SCI recipients. OUTCOME
      MEASURES: Unilateral auditory performance preimplantation and postimplantation
      was assessed. To compare interaural preimplantation performance, we defined a
      "better-hearing ear" as better pure tone average or speech awareness/reception
      threshold by at least 10 dB or open/closed-set speech perception score at least
      10 percentage points higher. RESULTS: Ninety patients underwent SCI from 1997 to
      2011; 34 children and 22 adults with at least 6 months of bilateral implant use
      underwent further analysis. Preoperatively, the first-implanted ear was better
      hearing in 6 cases, poorer hearing in 15 cases, and equal hearing in 35
      individuals. The proportion of SCI recipients exhibiting better long-term
      performance of the first-implanted ear was not significantly different from the
      proportion exhibiting equal or better performance of the second-implanted ear (p
      = 0.79, chi2), irrespective of preoperative hearing status. The first-implanted
      ear exhibited better closed/open-set speech perception scores in 41% (9/22) adult
      and 59% (20/34) pediatric patients at a mean most recent test point of 25 and 39
      months, respectively. CONCLUSION: Preimplantation unilateral hearing status was
      not found to influence relative interaural performance differences after SCI.
      This finding highlights the relative unimportance of preoperative audiometry and
      speech recognition scores for guiding clinical decisions regarding implant ear
      selection.

PMID- 24136308
TI  - Detecting soft failures in pediatric cochlear implants: relating behavior to
      language outcomes.
AB  - HYPOTHESIS: Undesirable behaviors in young children with cochlear implants
      suggest device soft failure. BACKGROUND: Cochlear implant soft failure refers to
      nonoptimal performance not detectable with routine hardware checks. Pediatric
      failures may delay language development, but failure detection is difficult. A
      2005 soft failure consensus statement recommended a checklist for suspected
      device malfunctions. That checklist included the appearance of "bad" behaviors
      and aggression (externalizing behaviors) or self-injury and inattentiveness
      (internalizing behaviors) as indicators of soft failure. Accordingly, these
      behaviors should predict slowed language growth, and the analyses reported here
      sought evidence of that predictive power. METHODS: Data from a longitudinal study
      of 80 children with cochlear implants collected at 6 times between 18 and 48
      months were reexamined. Language measures included auditory comprehension,
      expressive vocabulary, and unstructured language. A parent questionnaire, the
      Child Behavior Checklist, examined externalizing and internalizing behaviors.
      Behavior measures were correlated with language measures in a series of analyses.
      RESULTS: Externalizing and internalizing behaviors did not consistently correlate
      with language at the ages tested. Additionally, early behaviors did not predict
      later language abilities. Individual language measures correlated best with
      overall language development 12 months later. CONCLUSION: This study fails to
      support the hypothesis that externalizing and internalizing behaviors in
      pediatric cochlear implant users correlate with slowed language advance. These
      behaviors should not be seen as evidence of declining language performance as may
      be seen with device soft failure. Instead clinical assessments of language
      abilities are necessary.

PMID- 24136309
TI  - Immunohistochemical investigation of inducible nitric oxide synthase,
      osteopontin, and calcium-sensing receptor in a myringosclerosis/tympanosclerosis
      model.
AB  - HYPOTHESIS: To investigate roles of types of inflammation, inducible nitric oxide
      synthase (iNOS), osteopontin (OPN), and calcium sensing receptor (CaSR) in the
      tympanic membrane and middle ear in etiopathogenesis of
      myringosclerosis/tympanosclerosis (MT). BACKGROUND: Etiopathogenesis of
      myringosclerosis/tympanosclerosis is still unclear. Clinical and experimental
      observations demonstrate that hyperoxygenation might induce tympanosclerosis.
      METHODS: Seventy-five rats were divided into 3 groups: ventilation tube (VT)
      insertion, the Eustachian tube (ET) obliteration, and both procedures. Right ears
      were selected for mentioned interventions. Left ears served as controls. Then,
      histopathologic and immunohistochemical investigations were performed in tympanic
      bulla. MT and inflammation in tympanic membrane and middle ear space were
      investigated. Immunohistochemical investigation included staining with iNOS, OPN,
      and CaSR. RESULTS: Overall 42.7% of all rats developed MT. There was no
      significant difference in MT incidence among the groups (ET + VT group: 56%; ET
      group: 44%; VT group: 28%; p > 0.017). iNOS expression occurred in 30.6% of the
      intervention groups with insignificant differences (ET + VT group: 40%; ET
      group:36%; VT group:16%; p > 0.05). There was no significant difference in iNOS
      expression between tympanosclerotic (25%) and non tympanosclerotic ears (34.9%)
      (p = 0.359). OPN was expressed in 82.6% overall. It was the highest for ET group
      and ET + VT group (92% for each) followed by VT group (64%). There was a marginal
      significance in comparison of OPN staining between VT group and ET group and also
      between VT group and ET + VT group (p = 0.017). There was a significant
      difference in OPN expression between tympanosclerotic (100%) and
      nontympanosclerotic ears (69.8%) (p = 0.001). Neither control ears nor
      intervention groups showed CaSR expression. Comparisons of inflammation of the
      tympanic membrane and middle ear space between tympanosclerotic and non
      tympanosclerotic ears yielded significant differences (p = 0.003, p = 0.002,
      respectively). Tympanosclerotic ears had a tendency to show chronic or mixed
      inflammation in contrast to non-tympanosclerotic ears (p < 0.017). Filled-middle
      ear space was seen in 25% of the intervention groups with no significant
      difference (p > 0.017). There was a significant difference in the incidence
      between tympanosclerotic (46.8%) and non-tympanosclerotic ears (7%) (p < 0.017).
      CONCLUSION: Based on these findings, iNOS may not be evident in stage of MT. OPN
      staining is strongly associated with the development of MT. CaSR has no role in
      formation of MT. The results proved roles of mixed or chronic inflammation and
      the presence of the filled-middle ear in development of MT.

PMID- 24136310
TI  - Subtotal petrosectomy and mastoid obliteration in adult and pediatric cochlear
      implant recipients.
AB  - OBJECTIVE: To investigate the effect of subtotal petrosectomy and mastoid
      obliteration (SPMO) on the overall success of adult and pediatric cochlear
      implant (CI) recipients. STUDY DESIGN: Retrospective case series. SETTING:
      Tertiary care referral center. PATIENTS: Thirty-nine ears in 36 patients (23
      adults and 13 children) received both surgeries between 1990 and 2012.
      INTERVENTION: CI candidates underwent SPMO to permit implantation and minimize
      the risks of infectious complications in the recipient ear. SPMO was performed
      before (69.3%), at the time of (25.6%), and after CI (5.13%). Mastoids were
      obliterated with fat (30.8%), muscle (66.7%), and bone pate (2.56%). MAIN OUTCOME
      MEASURE: Feasibility, complications, and success of SPMO and CI were assessed
      with standard statistical analysis and Fisher's exact test with 2-sided p values.
      RESULTS: Ear disease was definitively managed, and CI was successfully placed in
      all but one case. Complications including abscess (n = 3), subcutaneous emphysema
      (n = 1), ear canal granulation formation (n = 1), and electrode extrusion (n = 1)
      occurred in 15.4% of patients. Predisposing syndromes were present in children
      more often than adults (43.8% versus 13.0%, p = 0.0598). Adults more often than
      children had previous mastoid surgery for middle ear disease (30.4% versus 0.0%,
      p = 0.0288). CIs were placed under local anesthetic and sedation (n= 3) and after
      radiation treatment for nasopharyngeal cancer (n = 2) in adult ears. CONCLUSION:
      SPMO is an effective and safe procedure for definitively managing middle ear
      disease and implanting adult and pediatric CI candidates.

PMID- 24136311
TI  - Importance of the brow in facial expressiveness during human communication.
AB  - OBJECTIVE: The objective of this study was to evaluate laterality and upper/lower
      face dominance of expressiveness during prescribed speech using a unique
      validated image subtraction system capable of sensitive and reliable measurement
      of facial surface deformation. RATIONALE: Observations and experiments of central
      control of facial expressions during speech and social utterances in humans and
      animals suggest that the right mouth moves more than the left during nonemotional
      speech. However, proficient lip readers seem to attend to the whole face to
      interpret meaning from expressed facial cues, also implicating a horizontal
      (upper face-lower face) axis. STUDY DESIGN: Prospective experimental design.
      Experimental maneuver: recited speech. OUTCOME MEASURE: image-subtraction
      strength-duration curve amplitude. METHODS: Thirty normal human adults were
      evaluated during memorized nonemotional recitation of 2 short sentences. Facial
      movements were assessed using a video-image subtractions system capable of
      simultaneously measuring upper and lower specific areas of each hemiface.
      RESULTS: The results demonstrate both axes influence facial expressiveness in
      human communication; however, the horizontal axis (upper versus lower face) would
      appear dominant, especially during what would appear to be spontaneous
      breakthrough unplanned expressiveness. CONCLUSION: These data are congruent with
      the concept that the left cerebral hemisphere has control over nonemotionally
      stimulated speech; however, the multisynaptic brainstem extrapyramidal pathways
      may override hemiface laterality and preferentially take control of the upper
      face. Additionally, these data demonstrate the importance of the often-ignored
      brow in facial expressiveness. LEVEL OF EVIDENCE: Experimental study. EBM levels
      not applicable.

PMID- 24136312
TI  - Radiographic features of superior semicircular canal dehiscence in the setting of
      chronic ear disease.
AB  - OBJECTIVE: To determine if radiologic chronic otitis media (COM), both with and
      without cholesteatoma, is associated with superior semicircular canal dehiscence
      (SSCD). STUDY DESIGN: Retrospective review of consecutive high-resolution
      computed tomography (HRCT) scans of the temporal bone. SETTING: Tertiary care
      medical center. PATIENTS: Two hundred consecutive patients undergoing HRCT of the
      temporal bone beginning January 1, 2012. INTERVENTION: Imaging was evaluated by 3
      reviewers (2 neuroradiologists and 1 neurotologist). All scans were assessed for
      the presence of SSCD, cholesteatoma, chronic otomastoiditis, tegmen dehiscence,
      and for abnormalities of the cochlea, vestibule, facial nerve, and temporal bone
      vasculature. MAIN OUTCOME MEASURE: Ears with COM associated with chronic
      otomastoiditis or cholesteatoma were compared with those without COM with respect
      to the presence of SSCD or other temporal bone abnormalities. Statistical
      analysis was performed to assess for differences between the groups studied.
      RESULTS: One-hundred ninety-four patients (388 ears) were included. Cholesteatoma
      was identified in 48 ears (12.4%) and chronic otomastoiditis in 62 ears (16%).
      Ten ears with cholesteatoma had ipsilateral SSCD, and 8 ears with chronic
      otomastoiditis had ipsilateral SSCD. In 340 ears without either cholesteatoma or
      chronic otomastoiditis, SSCD was found in 18 (5.3%). SSCD was found to occur
      significantly more often in patients with ipsilateral radiologic cholesteatoma.
      No cases of SSCD were associated with cochlear, facial nerve, or vascular
      abnormalities. CONCLUSION: Our findings suggest that COM with cholesteatoma is
      associated with the presence of SSCD, although the nature of this association is
      unclear.

PMID- 24136313
TI  - Unilateral cholesteatoma in the first millennium BC.
AB  - OBJECTIVE: To analyze the bone lesions of the ear region from a late Bronze Age
      individual to establish the most probable diagnosis. BACKGROUND: There has been
      evidence of diseases of the ear region since way back in history, but few human
      remains have been recognized. The case presented here corresponds to an ear
      lesion from a prehistoric skeleton found in the archeological site of La Cova des
      Pas (900-800 cal yr BC), located on Minorca island, in the western Mediterranean.
      METHODS: Macroscopic and radiologic (iCT) analysis had been performed. RESULTS:
      The remains belong to an elderly female subject who had a large cavity on the
      tympanic cavity as a result of the complete erosion of the outer wall of the
      attic and a large increase in the diameter of the outer ear canal. The cavity
      extends posterior to the mastoid. CONCLUSION: The diagnosis suggests a probable
      cholesteatoma, being one of the oldest cases in Europe.

PMID- 24136314
TI  - Spiral ganglion deficiency in adult-onset deafness-dystonia syndrome.

PMID- 24136315
TI  - Normative results of healthy older adults on standard clinical vestibular tests.
AB  - OBJECTIVE: To describe the performance of healthy older adults on common clinical
      vestibular tests. PATIENTS: Fifty community-dwelling older adults aged 70 and
      older, with mean age of 77.2 +/- 6.1 years and range of 70 to 95 years.
      INTERVENTION(S): Clinical vestibular tests, including spontaneous and head
      shaking nystagmus, head impulse test (HIT), bucket test of subjective visual
      vertical, modified Romberg test (MRT), and Dizziness Handicap Inventory (DHI).
      MAIN OUTCOME MEASURE(S): Prevalence of abnormal vestibular tests and DHI score.
      RESULTS: We observed a 36% and 44% prevalence of abnormal right and left
      horizontal HIT, respectively. The bucket test was abnormal in 18% of
      participants; head-shaking nystagmus was present in 2%, and no participant had
      spontaneous nystagmus. Approximately 68% of participants had abnormal MRT.
      Abnormal horizontal HIT and MRT were significantly more prevalent among
      individuals age 80 years and older compared with those age 70 to 79 years (p <
      0.05). Mean DHI score was 5.6 +/- 11.2, consistent with no self-reported
      dizziness handicap. CONCLUSION: This study documents the expected performance of
      normative older adults on vestibular tests commonly administered in the
      neurotology clinic. We observed a high prevalence of abnormalities on clinical
      vestibular testing in healthy older adults, although self-perceived dizziness
      handicap was low. Further studies using newly available clinical testing methods
      (e.g., video HIT) may identify finer gradations of vestibular function in older
      individuals and the levels of vestibular loss associated with functional
      impairment.

PMID- 24136316
TI  - Value of routine plain x-ray position checks after cochlear implantation.
AB  - OBJECTIVE: To analyze the value of a routine x-ray position check after cochlear
      implantation and to assess if an increased resistance during electrode insertion
      is a sufficient predictor of electrode misplacement. STUDY DESIGN: Retrospective
      data collection. SETTING: University hospital. METHODS: Plain x-rays (Stenvers'
      projection) and the respective surgery reports of 218 patients having received
      cochlear implantation (243 ears) were analyzed for possible electrode
      misplacements and intraoperative conspicuities during electrode insertion.
      RESULTS: Electrode misplacement (tip-over, loop, kinking, scalar transition, and
      incomplete insertion) was observed in 8% of the entire study cohort, but only in
      5% if cases with inner ear dysplasia or labyrinthine ossification (n = 28) were
      excluded from analysis. Intraoperatively, an increased resistance during
      electrode insertion was found in 16% but only in 8% when cases with inner ear
      dysplasia or labyrinthine ossification were excluded. The intraoperative finding
      of an increased resistance during electrode insertion had a sensitivity of 55%
      and a specificity of 88% for predicting radiographically confirmed electrode
      misplacements (positive predictive value, 29%; negative predicting value, 96%).
      CONCLUSION: Nearly half of the cases of electrode misplacement would have been
      overlooked if radiographic position checks would have been done only in patients
      with intraoperative conspicuities during electrode insertion. This finding
      advocates routine radiographic position checks, although electrode misplacements
      are relatively rare in patients with regular inner ear anatomy.

PMID- 24136317
TI  - Energy-dispersive X-ray microanalysis of poststapedotomy reparative granuloma.

PMID- 24136318
TI  - English consensus protocol evaluating candidacy for auditory brainstem and
      cochlear implantation in neurofibromatosis type 2.
AB  - OBJECTIVE: Hearing loss resulting from bilateral vestibular schwannomas (VSs) has
      a significant effect on the quality of life of patients with neurofibromatosis
      Type 2 (NF2). A national consensus protocol was produced in England as a guide
      for cochlear implantation (CI) and auditory brainstem implantation (ABI) in these
      patients. STUDY DESIGN: Consensus statement. SETTING: English NF2 Service.
      PARTICIPANTS: Clinicians from all 4 lead NF2 units in England. MAIN OUTCOME
      MEASURES: A protocol for the assessment, insertion and rehabilitation of CI and
      ABI in NF2 patients. RESULTS: Patients should undergo more detailed hearing
      assessment once their maximum aided speech discrimination score falls below 50%
      in the better hearing ear. Bamford-Kowal-Bench sentence testing scores below 50%
      should trigger assessment for auditory implantation, as recommended by the
      National Institute for Clinical Excellence guidelines on CI. Where this occurs in
      patients with bilateral stable VS or a unilateral stable VS where the
      contralateral cochlear nerve was lost at previous surgery, CI should be
      considered. Where VS surgery is planned, CI should be considered where cochlear
      nerve preservation is thought possible, otherwise an ABI should be considered.
      Intraoperative testing using electrically evoked auditory brainstem responses or
      cochlear nerve action potentials may be used to determine whether a CI or ABI is
      inserted. CONCLUSION: The NF2 centers in England agreed on this protocol.
      Multisite, prospective assessments of standardized protocols for auditory
      implantation in NF2 provide an essential model for evaluating candidacy and
      outcomes in this challenging patient population.

PMID- 24136319
TI  - Bilateral temporal bone otosyphilis.

PMID- 24136320
TI  - Anatomic parameters of the long process of incus for stapes surgery.
AB  - HYPOTHESIS: The purpose of this study is to offer new anatomic data about the
      long process of incus (LPI) for stapes surgery. BACKGROUND: Anatomic study of 50
      human macerated incudes to measure different parameters of cross sections of the
      LPI. METHODS: Step-by-step cutting of the LPI perpendicular to its axis starting
      from its free end next to the lenticular process. The layer thickness was 0.5 mm.
      The cutting surfaces were documented with Canon EOS 20D camera, and a standard
      software tool (MATLAB) was used for automated statistical analysis. RESULTS: The
      LPI had a maximum diameter of 1.15 mm and a minimum diameter of 0.52 mm at the
      level of 1.5 mm far from the tip of the long process, which is the most common
      site for stapes prosthesis attachment. Concerning each cross section, having a
      long and a short diameter, the average long diameter is 0.9011 mm, and the short
      diameter is 0.6507 mm. CONCLUSION: Our anatomic study revealed wide variations of
      diameters and shape of the LPI. Best possible crimping of stapes prosthesis
      depends not only on the shape and diameters of the LPI but also on the vertical
      surface of the LPI as well. To prevent incus necrosis due to compression of the
      feeding blood vessels, the maximum contact surface of the loop of stapes
      prosthesis should be about 1.9 mm in length.

PMID- 24136321
TI  - Split thickness skin grafting in canal wall down tympanomastoidectomy.
AB  - OBJECTIVE: To characterize the effects of a split thickness skin graft (STSG) on
      the healing of the mastoid cavity in patients undergoing canal wall down (CWD)
      procedures. STUDY DESIGN: A prospective randomized study. SETTING: Tertiary
      referral center. PATIENTS: Twenty-four patients, ages 21 to 82 years, with a
      diagnosis of cholesteatoma, undergoing CWD tympanomastoidectomy for the first
      time. INTERVENTION: Placement of a STSG to line the mastoid cavity at the time of
      surgery. MAIN OUTCOME MEASURES: The primary outcome was the amount of time
      required for epithelialization of the mastoid cavity. Secondary outcomes included
      postoperative complications, specifically, presence of otorrhea, granulation
      tissue, meatal stenosis, or tympanic membrane perforation. RESULTS: Twenty-four
      patients met inclusion criteria. Thirteen patients were randomized to the study
      group and 11 patients to the control group. Data were collected at follow-up
      appointments scheduled at postoperative Weeks 3, 6, 9, and 12, as well as every 6
      months thereafter. Average time for successful epithelialization of the cavity in
      the STSG group was 3.2 weeks. Average time for successful epithelialization of
      the control group was 6.6 weeks. Using a 1-sided 2 sample t test, this was found
      to be statistically significant with a p value of 0.000137. There was no
      significant difference in complications rates between the 2 groups. CONCLUSION:
      Placement of a STSG is a technique available to the otologist to facilitate rapid
      healing and epithelialization in patients undergoing CWD tympanomastoidectomy.

PMID- 24136322
TI  - Evaluation of vascular activity in otosclerosis by laser Doppler flowmetry:
      comparison with computed tomographic densitometry.
AB  - OBJECTIVE: To evaluate vascular activity in ears with otosclerosis by
      intraoperative measurement of blood flow using laser Doppler flowmetry and to
      compare the data with densitometry on computed tomography (CT). DESIGN:
      Retrospective case series. SETTING: University hospital. PATIENTS: Thirty-nine
      ears from 33 patients who underwent surgery for otosclerosis. INTERVENTION: The
      subjects were divided into fenestral (29 ears) and retrofenestral (10 ears)
      groups based on CT findings. Ratios of bone density in the area anterior to the
      oval window (AOW) or the promontory (PT) near the round window niche to that of
      the basis labyrinthine otic capsule were calculated on CT images. Measurements of
      blood flow were performed with a laser Doppler flowmeter at the 2 corresponding
      areas evaluated by CT. MAIN OUTCOME MEASURES: Imaging and blood flow values.
      RESULTS: In both groups, relatively young subjects with high blood flow values in
      the AOW or PT had rather low ratios of bone density in the corresponding areas.
      In contrast, old subjects with low ratios of bone density showed low blood flow
      values in the same areas. In the retrofenestral group, subjects with high blood
      flow values in the PT showed low blood flow values in the AOW, but their ratios
      of bone density were similarly low in both areas. CONCLUSION: Blood flow varied
      and did not correlate with CT densitometry. Measurement of blood flow by laser
      Doppler flowmetry could yield useful information to evaluate the progress of
      vascular activity.

PMID- 24136323
TI  - Extension of indications for transcanal endoscopic ear surgery using an
      ultrasonic bone curette for cholesteatomas.
AB  - BACKGROUND: One-handed endoscopic procedures have, up until now, limited the
      indications for transcanal endoscopic ear surgery (TEES) in cholesteatoma
      surgery. However, the development of electrically powered instruments has opened
      the door to such one-handed endoscopic procedures in restricted surgical spaces.
      OBJECTIVE: We examined the feasibility of using one such powered instrument, the
      ultrasonic bone curette (UBC) in TEES for cholesteatoma surgery. The UBC offers
      several advantages, including nonrotational motion and the combination of both
      suction and irrigation in a single handpiece. STUDY DESIGN: A prospective case
      series. SETTING: Tertiary referral center. PATIENTS: TEES was performed on 43
      cases of primary cholesteatoma between September 2011 and December 2012,
      including 14 cases extending to the antrum. INTERVENTION: Zero-, 30-, or 70
      degree angled rigid endoscopes with an outer diameter of 2.7 mm (Karl Storz) were
      used together with a high-definition video system. A Sonopet UBC (Stryker) was
      used to cut bony tissue. The nonrotational motion of the UBC prevents injury to
      the tympanomeatal flap and other soft tissue, which may result with standard
      drills. Transcanal endoscopic retrograde mastoidectomy on demand was performed to
      access the pathologies in the attic and antrum. RESULTS: A minimum attico
      antrotomy was performed using the UBC, removing only the bony tissue necessary to
      visualize the pathology. The cholesteatoma was completely removed from the antral
      mucosa under clear endoscopic visualization in 13 of 14 cases. After removal of
      the cholesteatoma, the canal wall was reconstructed using cartilage taken from
      the tragus. This procedure resulted in greater mastoid preservation. CONCLUSION:
      The transcanal endoscopic approach to the antrum using the UBC proved to be less
      invasive and more functional. The UBC contains both a suction and irrigation
      system in a single handpiece, and this UBC is an appropriate cutting tool that
      extends the indications for TEES.

PMID- 24136324
TI  - Long-term results of canal wall reconstruction tympanomastoidectomy.
AB  - OBJECTIVES: This study was designed to evaluate the long-term results using the
      technique of canal wall reconstruction (CWR) tympanomastoidectomy with mastoid
      obliteration in the treatment of chronic otitis media with cholesteatoma. STUDY
      DESIGN: Institutional review board-approved retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: Retrospective review was performed on
      consecutive patients undergoing CWR tympanomastoidectomy with mastoid
      obliteration at a single institution from 1997 to 2011. MAIN OUTCOME MEASURES:
      Status of tympanic membrane and ear canal anatomy, preoperative and postoperative
      audiometry, residual cholesteatoma at second look surgery, postoperative
      complications, recurrence rate, and location. RESULTS: Two hundred eighty-five
      ears in 273 patients underwent CWR tympanomastoidectomy with a mean age of 35
      years with average follow-up of 4.29 years (median, 3.16 yr). A second-look
      ossiculoplasty was performed in 253 (89%). Recurrent retraction pocket formation
      occurred in 34 ears (13%). A secondary endaural atticotomy only was required to
      improve access for debridement in 16 of these 34 ears (5.8% of total ears). Only
      7 ears (2.6%) required a revision open cavity mastoidectomy (n = 5) or subtotal
      petrosectomy (n = 2) for recurrent cholesteatoma. Those undergoing second-look
      ossiculoplasty demonstrated a small improvement in preoperative versus
      postoperative air-bone gap (ABG), 28 dB versus 23 dB, respectively. Postoperative
      infection occurred in 16 patients (5.6%) with 1 patient requiring conversion to
      open cavity mastoidectomy. CONCLUSION: A CWR tympanomastoidectomy provides
      excellent intraoperative exposure of the middle ear and mastoid without the long
      term disadvantages of a canal wall down mastoidectomy. Long-term follow-up
      demonstrates that there were only 2.6% failures requiring conversion to an open
      cavity or subtotal petrosectomy. LEVEL OF EVIDENCE: 4.

PMID- 24136325
TI  - Factors affecting fenestration of the footplate in stapes surgery: effectiveness
      of Fisch's reversal steps stapedotomy.
AB  - OBJECTIVE: To analyze the factors affecting the fenestration of the footplate in
      stapes surgery and to evaluate the effectiveness of Fisch's reversal steps
      stapedotomy. STUDY DESIGN: Retrospective study. PATIENTS: A total of 191 patients
      with otosclerosis in whom 230 primary stapes surgeries were performed by 1
      surgeon in 3 tertiary hospitals. MAIN OUTCOME MEASURE: Evaluation of factors
      affecting the fenestration of the footplate in stapes surgery by logistic
      regression analysis. RESULTS: Stapedotomy (small hole in stapes footplate) was
      performed in 148 ears (64.3%). Partial stapedectomy (half removal of stapes
      footplate) was performed in 65 ears (28.3%). Total stapedectomy (total removal of
      stapes footplate) was performed in 17 ears (7.4%). Stapedotomy could be performed
      in 72.1% of cases (75/104) in which the stapes suprastructure was removed after
      insertion of the prosthesis and in 57.9% of cases (73/126) in which the stapes
      suprastructure was removed before the insertion. Stapedotomy could be performed
      in 65.4% of cases (117/179) in which a 0.6-mm-thick Schuknecht-type Teflon wire
      piston was used and in 60.8% (31/51) in which a whole Teflon piston was used.
      Multivariate analysis of factors affect stapedotomy using logistic regression
      analysis showed that the surgical order of the removal of the stapes
      suprastructure and insertion of the prosthesis were the most important 2 factors.
      CONCLUSION: Fisch's reversal steps technique was useful in performing stapedotomy
      in all otosclerosis patients. Manipulation of the prosthesis when crimping it to
      the incus is also important. The prosthesis should be crimped onto the incus and
      inserted in the footplate opening gently and atraumatically.

PMID- 24136326
TI  - Optimizing total facial nerve patient management for effective clinical outcomes
      research.
AB  - IMPORTANCE: Assessment of outcomes in patients with facial paralysis is
      challenging owing to the lack of objective tools to evaluate facial function and
      suboptimal data collection. OBJECTIVE: To describe a methodology for prospective
      evaluation of patients with facial paralysis that permits optimal assessment of
      clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: At the Massachusetts Eye
      and Ear Infirmary, we have treated over 2000 patients with facial nerve injury
      since 2002. To better quantify and improve our outcomes, we have developed what
      we now believe represents a systematic method for the previsit evaluation,
      intake, management, and follow-up of our facial nerve patients to optimize data
      collection for the purposes of clinical outcome studies, as detailed in this
      retrospective descriptive study. RESULTS: Data collection is often poor if there
      is not a specific individual delegated to the task and is particularly
      challenging in the intraoperative setting. Retrospective acquisition of data are
      inherently less accurate and time consuming. A user-friendly searchable database
      is required to use the collected data. CONCLUSIONS AND RELEVANCE: Clinical
      outcomes research in the field of facial paralysis requires meticulous attention
      to comprehensive data collection at appropriate time points, precision
      photography, and the use of available quality of life and objective measurement
      tools. Ideally, a standardized approach for data collection would be adopted that
      would permit multi-institutional data analysis to improve the quality of outcomes
      research currently available. LEVEL OF EVIDENCE: NA.

PMID- 24136327
TI  - Importance of the three basic residues in the vicinity of the zinc-binding motifs
      for the activity of the yeast dipeptidyl peptidase III.
AB  - Yeast dipeptidyl peptidase III (yDPP III) is a member of the metallopeptidase
      family M49 involved in intracellular protein catabolism. Elucidation of the yDPP
      III crystal structure has pinpointed the zinc-coordinating residues (two His from
      H(460)ELLGH(465) motif and the second Glu from E(516)ECRAE(521) motif), and
      several amino acid residues potentially important for catalytic activity whose
      roles have not been investigated. Here, three putative catalytic residues of the
      yDPP III, His578, Arg582 and Lys638 were substituted and the resultant single
      mutants characterized. The replacement of His578 with an asparagine significantly
      (122-fold) lowered the catalytic efficiency, kcat/Km, for Arg-Arg-2-naphthylamide
      (Arg2-2NA) hydrolysis, and affinity for hydroxamate inhibitor Tyr-Phe-NHOH
      (decline by 14-fold). The R582Q mutant exhibited an order of magnitude higher
      activity with all four dipeptide derivatives examined, compared to the wild type.
      The molecular dynamics simulations revealed the change in the H-bond networking
      in the R582Q variant active-site region. The mutation of Lys638, to Leu, slightly
      increased the specificity constant for Arg2-2NA hydrolysis. However, the affinity
      for Tyr-Phe-NHOH, and activity for the substrates with uncharged P2 side chains
      (Ala-Ala-, Ala-Arg- and Phe-Arg-2NA) were dramatically reduced, indicating the
      importance of the evolutionary conserved salt bridge Lys(638)-Glu(516) for the
      modulation of DPP III substrate specificity.

PMID- 24136328
TI  - The consequences of proportional hazards based model selection.
AB  - For testing the efficacy of a treatment in a clinical trial with survival data,
      the Cox proportional hazards (PH) model is the well-accepted, conventional tool.
      When using this model, one typically proceeds by confirming that the required PH
      assumption holds true. If the PH assumption fails to hold, there are many options
      available, proposed as alternatives to the Cox PH model. An important question
      which arises is whether the potential bias introduced by this sequential model
      fitting procedure merits concern and, if so, what are effective mechanisms for
      correction. We investigate by means of simulation study and draw attention to the
      considerable drawbacks, with regard to power, of a simple resampling technique,
      the permutation adjustment, a natural recourse for addressing such challenges. We
      also consider a recently proposed two-stage testing strategy (2008) for
      ameliorating these effects.

PMID- 24136329
TI  - A GPS map for pulmonary hypertension: a review of imaging modalities.
AB  - Pulmonary hypertension (PH) is a lethal disease with a prevalence of 10-20 % in
      the general population. The current gold standard diagnosis approach is right
      heart catheterization, directly detecting pulmonary artery pressure. Imaging for
      PH patients plays an important role in the etiological diagnosis and evaluation
      of right heart (RV) function, which is a key determinant of morbidity and
      mortality in PH patients. Currently, echocardiography is the first-line imaging
      modality for screening PH and evaluating RV function. CMRI is the gold standard
      method to evaluate RV function. MDCT, radionuclide ventriculography and pulmonary
      angiography are mostly used in the differential diagnosis of the cause of PH. In
      this review article, we also mention several newly studied imaging modalities,
      such as three-dimensional echocardiography, intravascular ultrasound (IVUS) and
      optical coherence tomography (OCT), which showed promise for early diagnosis of
      PH. 

PMID- 24136330
TI  - Once-daily fluticasone furoate alone or combined with vilanterol in persistent
      asthma.
AB  - The inhaled corticosteroid fluticasone furoate (FF) and the long-acting beta2
      agonist vilanterol (VI) are in development as a combined once-daily therapy for
      asthma and chronic obstructive pulmonary disease. Our study objectives were to
      compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily
      fluticasone propionate (FP) in patients aged >=12 years with moderate-to-severe
      persistent asthma. Patients (n=586) received FF/VI 200/25 MUg or FF 200 MUg once
      daily (evening dosing), or FP 500 MUg twice-daily for 24 weeks. Co-primary end
      points were change from baseline in trough forced expiratory volume in 1 s (FEV1)
      weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from
      baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24
      h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety
      assessments included adverse events, 24-h urinary cortisol excretion, vital signs
      and ECG. FF/VI significantly improved trough FEV1 and wmFEV1 versus FF and FP.
      Significantly more rescue-free and symptom-free 24-h periods were reported with
      FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence
      of adverse events was similar across groups. No clinically significant
      differences were seen for 24-h urinary cortisol excretion, vital signs or ECG.
      FF/VI resulted in statistically greater improvements in lung function and
      symptomatic end-points versus FF, and was well tolerated in this asthma
      population.

PMID- 24136331
TI  - Pulmonary arterial hypertension in familial hemiplegic migraine with ATP1A2
      channelopathy.

PMID- 24136333
TI  - Plasma interleukin-6 adds prognostic information in pulmonary arterial
      hypertension.

PMID- 24136334
TI  - Elevated expression of the NLRP3 inflammasome in neutrophilic asthma.
AB  - Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)
      1beta is thought to be a key mediator, especially in the neutrophilic subtype of
      asthma. The generation of active IL-1beta requires proteolytic cleavage typically
      mediated through the formation of a caspase-1-containing inflammasome. This study
      hypothesised that an IL-1beta endotype associated with the nucleotide-binding
      domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis
      associated speck-like protein containing a caspase-recruitment domain
      (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic
      subtype of asthma. Participants with asthma (n=85) and healthy controls (n=27)
      underwent clinical assessment, spirometry and sputum induction. Sputum was
      processed for differential cell count, gene expression and protein mediators.
      NLRP3 and caspase-1 expression was also determined by immunocytochemistry. Sputum
      macrophages were isolated (n=8) and gene expression of NLRP3 and IL-1beta
      determined. There was significantly elevated gene expression of NLRP3, caspase-1,
      caspase-4, caspase-5 and IL-1beta in participants with neutrophilic asthma.
      Protein levels of IL-1beta were significantly higher in those with neutrophilic
      asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as
      sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein.
      NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the
      inflammation process observed in this asthma phenotype through production of IL
      1beta.

PMID- 24136335
TI  - Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3
      mutations.

PMID- 24136336
TI  - Leptin and adiponectin: emerging therapeutic targets in breast cancer.
AB  - Obesity is a recognized risk factor for breast cancer development and poorer
      response to therapy. Two major fat tissue-derived adipokines, leptin and
      adiponectin have been implicated in mammary carcinogenesis. Leptin appears to
      promote breast cancer progression through activation of mitogenic, antiapoptotic,
      and metastatic pathways, while adiponectin may restrict tumorigenic processes
      primarily by inhibiting cell metabolism. Furthermore, adiponectin is known to
      counteract detrimental leptin effects in breast cancer models. Thus, therapeutic
      inhibition of pro-neoplastic leptin pathways and reactivation of anti-neoplastic
      adiponectin signaling may benefit breast cancer patients, especially the obese
      subpopulation. This review focuses on current experimental strategies aiming at
      leptin and adiponectin pathways in breast cancer models. Novel leptin receptor
      antagonists and adiponectin receptor agonists as well as other compounds for
      therapeutic modulation of adipokine pathways are discussed in detail, including
      potential pharmacological advantages and limitations of these approaches. 

PMID- 24136332
TI  - Tumour necrosis factor receptor-75 and risk of COPD exacerbation in the
      azithromycin trial.

PMID- 24136338
TI  - Axial prestretch and circumferential distensibility in biomechanics of abdominal
      aorta.
AB  - Elastic arteries are significantly prestretched in an axial direction. This
      property minimises axial deformations during pressure cycle. Ageing-induced
      changes in arterial biomechanics, among others, are manifested via a marked
      decrease in the prestretch. Although this fact is well known, little attention
      has been paid to the effect of decreased prestretch on mechanical response. Our
      study presents the results of an analytical simulation of the inflation-extension
      behaviour of the human abdominal aorta treated as nonlinear, anisotropic,
      prestrained thin-walled as well as thick-walled tube with closed ends. The
      constitutive parameters and geometries for 17 aortas adopted from the literature
      were supplemented with initial axial prestretches obtained from the statistics of
      365 autopsy measurements. For each aorta, the inflation-extension response was
      calculated three times, with the expected value of the initial prestretch and
      with the upper and lower confidence limit of the initial prestretch derived from
      the statistics. This approach enabled age-related trends to be evaluated bearing
      in mind the uncertainty in the prestretch. Despite significantly decreased
      longitudinal prestretch with age, the biomechanical response of human abdominal
      aorta changes substantially depending on the initial axial stretch was used. In
      particular, substituting the upper limit of initial prestretch gave mechanical
      responses which can be characterised by (1) low variation in axial stretch and
      (2) high circumferential distensibility during pressurisation, in contrast to the
      responses obtained for their weakly prestretched counterparts. The simulation
      also suggested the significant effect of the axial prestretch on the variation of
      axial stress in the pressure cycle. Finally, the obtained results are in
      accordance with the hypothesis that circumferential-to-axial stiffness ratio is
      the quantity relatively constant within this cycle. 

PMID- 24136337
TI  - Serotonin and serotonin transport in the regulation of lactation.
AB  - Serotonin (5-HT), classically known as a neurotransmitter involved in regulating
      sleep, appetite, memory, sexual behavior, neuroendocrine function and mood is
      also synthesized in epithelial cells located in many organs throughout the body,
      including the mammary gland. The function of epithelial 5-HT is dependent on the
      expression of the 5-HT receptors in a particular system. The conventional
      components of a classic 5-HT system are found within the mammary gland; synthetic
      enzymes (tryptophan hydroxylase I, aromatic amino acid decarboxylase), several 5
      HT receptors and the 5-HT reuptake transporter (SERT). In the mammary gland, two
      actions of 5-HT through two different 5-HT receptor subtypes have been described:
      negative feedback on milk synthesis and secretion, and stimulation of parathyroid
      hormone related-protein, a calcium-mobilizing hormone. As with neuronal systems,
      the regulation of 5-HT activity is multifactorial, but one seminal component is
      reuptake of 5-HT from the extracellular space following its release. Importantly,
      the wide availability of selective 5-HT reuptake inhibitors (SSRI) allows the
      manipulation of 5-HT activity in a biological system. Here, we review the role of
      5-HT in mammary gland function, review the biochemistry, genetics and physiology
      of SERT, and discuss how SERT is vital to the function of the mammary gland.

PMID- 24136339
TI  - Development and validation of a fall-related impulsive behaviour scale for
      residential care.
AB  - INTRODUCTION: impulsivity in older people with cognitive impairment has yet to be
      examined rigorously as a risk factor for falls. The objective of this study was
      to evaluate the psychometric properties of a new fall-related impulsive behaviour
      scale (FIBS) for a cognitively impaired population living in residential care.
      METHODS: one hundred and nine care home residents (84.5 +/- 8.3 years) were
      assessed on the FIBS and a range of behavioural, physical and neuropsychological
      measures. Participants were then prospectively followed up for falls for 6
      months. RESULTS: the internal reliability (Cronbach's alpha = 0.77) and test
      retest reliability (intra-class correlation coefficient = 0.93) of the FIBS were
      both good. Construct validity was supported by significant correlations between
      the FIBS and the neuropsychiatric inventory (r = 0.43, P < 0.001), wandering (r =
      0.33, P = 0.001) and global cognition (r = -0.2, P = 0.04). Compared with
      residents with FIBS scores <1, those with FIBS scores of >= 1 were nearly three
      times more likely to fall in the following 6 months, AOR = 2.92 (95% CI: 1.03
      8.29). CONCLUSION: the FIBS is a simple, valid and reliable scale for assessing
      fall-related impulsivity in care home residents and can be recommended for use in
      this group for both research and clinical purposes.

PMID- 24136340
TI  - Education associated with a delayed onset of terminal decline.
AB  - BACKGROUND: the terminal decline hypothesis suggests an acceleration in the rate
      of loss of cognitive function before death. Evidence about the association of
      educational attainment and the onset of terminal decline is scarce. OBJECTIVE: to
      investigate the association of education with the onset of terminal decline in
      global cognitive function measured by Mini Mental State Exam (MMSE) scores.
      SUBJECTS: deceased participants of the Cambridge City over 75 Cohort Study who
      were interviewed at about 2, 7, 9, 13, 17 and 21 years after baseline. METHODS:
      regular and Tobit random change point growth models were fitted to MMSE scores to
      identify the onset of terminal decline and assess the effect of education on this
      onset. RESULTS: people who left school at an older age had a delayed onset of
      terminal decline. Thus better educated individuals experience a slightly shorter
      period of faster decline before death. CONCLUSION: an important finding emerging
      from our work is that education does appear to delay the onset of terminal
      decline, although only by a limited amount.

PMID- 24136341
TI  - Re: trends in hip fracture incidence and mortality in Chinese population from
      Hong Kong 2001-09.

PMID- 24136342
TI  - Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA)
      consensus conference on classification, diagnosis, management, and future
      research.
AB  - The American Society for Apheresis (ASFA) conducted a 1 day consensus conference
      on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in
      Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of
      ASFA's Clinical Applications Committee, developed several questions with regard
      to definitions, classification, pathophysiology, diagnosis, management, and
      future research in TTP. These questions were provided to the seven invited
      speakers who are the experts in the field of TTP. Two moderators conducted the
      proceedings of the conference which was attended by more than 100 participants.
      After each presentation, there was an open discussion that included moderator
      selected written questions submitted by the audience. A medical writer-generated
      transcript of the proceedings as well as each presentation was made available to
      the authors. Each summary was reviewed and approved by the respective speaker
      before submission of this article. The subcommittee also developed seven key
      questions for blinded, electronic polling conducted by the moderators to generate
      a consensus amongst the speakers. This article includes these presentation
      summaries as well as results of the electronic poll.

PMID- 24136343
TI  - Bacterial and fungal taxon changes in soil microbial community composition
      induced by short-term biochar amendment in red oxidized loam soil.
AB  - To take full advantage of biochar as a soil amendment, the objective of this
      study was to investigate the effects of biochar addition on soil bacterial and
      fungal diversity and community composition. Incubation experiments with a forest
      soil (a red oxidized loam soil) with and without biochar amendment were conducted
      for 96 days. The culture-independent molecular method was utilized to analyze
      soil bacterial and fungal species after the incubation experiments. Results
      showed that bacteria and fungi responded differently to the biochar addition
      during the short-term soil incubation. Twenty four and 18 bacterial genara were
      observed in the biochar amended and unamended soils, respectively, whereas 11 and
      8 fungal genera were observed in the biochar amended and unamended soils,
      respectively. Microbial taxa analysis indicated that the biochar amendment
      resulted in significant shifts in both bacterial and fungal taxa during the
      incubation period. The shift for bacteria occurred at the genus and phylum
      levels, while for fungi only at the genus level. Specific taxa, such as
      Actinobacteria of bacteria and Trichoderma and Paecilomyces of fungi, were
      enriched in the biochar amended soil. The results reveal a pronounced impact of
      biochar on soil microbial community composition and an enrichment of key
      bacterial and fungal taxa in the soil during the short time period.

PMID- 24136344
TI  - Reduced effects of tendon vibration with increased task demand during active,
      cyclical ankle movements.
AB  - Tendon vibration can alter proprioceptive feedback, one source of sensory
      information which humans can use to produce accurate movements. However, the
      effects of tendon vibration during functional movement vary depending on the
      task. For example, ankle tendon vibration has considerably smaller effects during
      walking than standing posture. The purpose of this study was to test whether the
      effects of ankle tendon vibration are predictably influenced by the mechanical
      demands of a task, as quantified by peak velocity. Twelve participants performed
      symmetric, cyclical ankle plantar flexion/dorsiflexion movements while lying
      prone with their ankle motion unconstrained. The prescribed movement period (1, 3
      s) and peak-to-peak amplitude (10 degrees , 15 degrees , 20 degrees ) were varied
      across trials; shorter movement periods or larger amplitudes increased the peak
      velocity. In some trials, vibration was continuously and simultaneously applied
      to the right ankle plantar flexor and dorsiflexor tendons, while the left ankle
      tendons were never vibrated. The vibration frequency (40, 80, 120, 160 Hz) was
      varied across trials. During trials without vibration, participants accurately
      matched the movement of their ankles. The application of 80 Hz vibration to the
      right ankle tendons significantly reduced the amplitude of right ankle movement.
      However, the effect of vibration was smaller during more mechanically demanding
      (i.e., higher peak velocity) movements. Higher vibration frequencies had larger
      effects on movement accuracy, possibly due to parallel increases in vibration
      amplitude. These results demonstrate that the effects of ankle tendon vibration
      are dependent on the mechanical demand of the task being performed, but cannot
      definitively identify the underlying physiological mechanism.

PMID- 24136345
TI  - CRISPR interference (CRISPRi) for sequence-specific control of gene expression.
AB  - Sequence-specific control of gene expression on a genome-wide scale is an
      important approach for understanding gene functions and for engineering genetic
      regulatory systems. We have recently described an RNA-based method, CRISPR
      interference (CRISPRi), for targeted silencing of transcription in bacteria and
      human cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR
      (clustered regularly interspaced palindromic repeats) pathway, requiring only the
      coexpression of a catalytically inactive Cas9 protein and a customizable single
      guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to
      the sgRNA and causes a steric block that halts transcript elongation by RNA
      polymerase, resulting in the repression of the target gene. Here we provide a
      protocol for the design, construction and expression of customized sgRNAs for
      transcriptional repression of any gene of interest. We also provide details for
      testing the repression activity of CRISPRi using quantitative fluorescence assays
      and native elongating transcript sequencing. CRISPRi provides a simplified
      approach for rapid gene repression within 1-2 weeks. The method can also be
      adapted for high-throughput interrogation of genome-wide gene functions and
      genetic interactions, thus providing a complementary approach to RNA
      interference, which can be used in a wider variety of organisms. 

PMID- 24136346
TI  - Laser-induced choroidal neovascularization model to study age-related macular
      degeneration in mice.
AB  - The mouse model of laser-induced choroidal neovascularization (CNV) has been used
      extensively in studies of the exudative form of age-related macular degeneration
      (AMD). This experimental in vivo model relies on laser injury to perforate
      Bruch's membrane, resulting in subretinal blood vessel recruitment from the
      choroid. By recapitulating the main features of the exudative form of human AMD,
      this assay has served as the backbone for testing antiangiogenic therapies. This
      standardized protocol can be applied to transgenic mice and can include
      treatments with drugs, recombinant proteins, antibodies, adenoviruses and pre
      microRNAs to aid in the search for new molecular regulators and the
      identification of novel targets for innovative treatments. This robust assay
      requires 7-14 d to complete, depending on the treatment applied and whether
      immunostaining is performed. This protocol includes details of how to induce CNV,
      including laser induction, lesion excision, processing and different approaches
      to quantify neoformed vasculature. 

PMID- 24136347
TI  - Selective ribosome profiling as a tool for studying the interaction of chaperones
      and targeting factors with nascent polypeptide chains and ribosomes.
AB  - A plethora of factors is involved in the maturation of newly synthesized
      proteins, including chaperones, membrane targeting factors and enzymes. Many
      factors act co-translationally through association with ribosome-nascent chain
      complexes (RNCs), but their target specificities and modes of action remain
      poorly understood. We developed selective ribosome profiling (SeRP) to identify
      substrate pools and points of RNC engagement of these factors. SeRP is based on
      sequencing mRNA fragments covered by translating ribosomes (general ribosome
      profiling (RP)), combined with a procedure to selectively isolate RNCs whose
      nascent polypeptides are associated with the factor of interest. Factor-RNC
      interactions are stabilized by cross-linking; the resulting factor-RNC adducts
      are nuclease-treated to generate monosomes, and then they are affinity purified.
      The ribosome-extracted mRNA footprints are converted to DNA libraries for deep
      sequencing. The protocol is specified for general RP and SeRP in bacteria. It was
      first applied to the chaperone trigger factor (TF) and is readily adaptable to
      other co-translationally acting factors, including eukaryotic factors. Factor-RNC
      purification and sequencing library preparation takes 7-8 d, and sequencing and
      data analysis can be completed in 5-6 d. 

PMID- 24136348
TI  - Simultaneous isolation of high-quality DNA, RNA, miRNA and proteins from tissues
      for genomic applications.
AB  - Genomic technologies have revolutionized our understanding of complex Mendelian
      diseases and cancer. Solid tumors present several challenges for genomic
      analyses, such as tumor heterogeneity and tumor contamination with surrounding
      stroma and infiltrating lymphocytes. We developed a protocol to (i) select
      tissues of high cellular purity on the basis of histological analyses of
      immediately flanking sections and (ii) simultaneously extract genomic DNA (gDNA),
      mRNA, noncoding RNA (ncRNA; enriched in miRNA) and protein from the same tissues.
      After tissue selection, about 12-16 extractions of DNA, RNA or protein can be
      obtained per day. Compared with other similar approaches, this fast and reliable
      methodology allowed us to identify mutations in tumors with remarkable
      sensitivity and to perform integrative analyses of whole-genome and exome data
      sets, DNA copy numbers (by single-nucleotide polymorphism (SNP) arrays), gene
      expression data (by transcriptome profiling and quantitative PCR (qPCR)) and
      protein levels (by western blotting and immunohistochemical analysis) from the
      same samples. Although we focused on renal cell carcinoma, this protocol may be
      adapted with minor changes to any human or animal tissue to obtain high-quality
      and high-yield nucleic acids and proteins. 

PMID- 24136349
TI  - Alterations of selected iron management parameters and activity in food
      restricted female Wistar rats (animal anorexia models).
AB  - AIMS: The aim of this study was to assess the influence of food-restricted diets
      (anorexia models) on iron management and activity of rats. MATERIALS AND METHODS:
      48 rats were divided into 6 groups: 1 control (K) and 5 testing groups (K/2, GI,
      GII, GIII, GIV). K was fed ad libitum. K/2 received half the portion of the diet
      of K. The other groups received 100% of the diet eaten by K, but with different
      models of food restriction: GI-1 day on, 1 day starvation; GII-2 days on, 2 days
      starvation; GIII-3 days on, 3 days starvation; and GIV-4 days on, 4 days
      starvation. As a result, all testing groups ate half of the diet consumed by the
      control group. The concentrations of iron in selected tissues, ferritin, and
      selected iron management parameters in blood were examined, as well as the
      animals' activities associated with food craving. RESULTS: The animal anorexia
      models used in this study had a significant influence on the blood concentrations
      of hemoglobin (p < 0.01), hematocrit (p < 0.05), RBC (p < 0.05), iron levels in
      liver (p < 0.05), kidney (p < 0.001), and heart (p < 0.05), the serum ferritin
      concentration (p < 0.001) and the rats activity (p < 0.001); whereas there was no
      influence on the other parameters. Generally, the statistically negative effects
      of starvation models on iron management parameters and activity of animals were
      observed. However, these effects were dependent on the model of anorexia more
      than on the quantity of food intake. CONCLUSIONS: The negative effect of food
      deprivation on iron deficiency and rat activities were observed in all groups;
      however, the strongest effect was noticed in those animals subject to chronic
      starvation. Acute deprivations caused the reduction of activity in the rats,
      however, chronic starvation caused an increase in the activity of the first phase
      of the experiment, followed by a decline in the subsequent phase. It is possible
      that stress and frustration as well as depression may be caused by insufficient
      food intake, and as a result, by iron deficiency in a diet similar to human
      anorexia. However, more animal/human comparison studies are necessary.

PMID- 24136350
TI  - The relationship of selenium tolerance and speciation in Lecythidaceae species.
AB  - Comparative study of selenium (Se) speciation in hyperaccumulator plants offers
      an interesting challenge from the analytical point of view. In our study the
      application of a sophisticated sample clean-up procedure and the combination of
      elemental and molecular mass spectrometric methods led to the identification of
      several new selenocompounds. The difference between the Se speciation of the
      primary accumulator Lecythis minor and the secondary accumulator Bertholletia
      excelsa confirmed the current opinion that the speciation pattern in
      hyperaccumulator plants is principally related to the mechanism of accumulation
      and not to taxonomy. The most abundant new selenocompounds were found to be the
      derivatives of selenohomocysteine (SeHCy) and selenomethionine (SeMet), including
      fatty acid metabolism related compounds. A series of SeHCy derived species
      containing multiple Se atoms (>2) was also detected and their structures were
      validated by the synthesis of their S-Se analogues. 

PMID- 24136351
TI  - Functional extracellular eosinophil granules: a bomb caught in a trap.
AB  - Eosinophils store a wide range of preformed proteins, including cationic proteins
      and cytokines, within their morphologically unique granules. Recently, we have
      demonstrated that cell-free eosinophil granules are functional, independent,
      secretory organelles and that clusters of cell-free granules are commonly found
      at tissue sites associated with various pathologic conditions. Cytolytic release
      of intact eosinophil granules produces extracellular organelles that are fully
      capable of ligand-elicited, active, secretory responses and are hence able to act
      as 'cluster bombs' that amplify the differential secretory properties of
      eosinophils. Herein, we review recent progress in elucidating the molecular
      mechanisms involved in the cytolytical release of intact cell-free functional
      eosinophil granules in a process associated with the liberation of eosinophil DNA
      traps (nets), a known aspect of the innate response recognized in various immune
      cells and pathological conditions. We also discuss the importance of clusters of
      cell-free eosinophil granules trapped in eosinophil DNA nets in disease and
      speculate on their potential role(s) in immunity as well as compare available
      data on DNA-releasing neutrophils.

PMID- 24136352
TI  - Can I access my personal genome? The current legal position in the UK.
AB  - This paper discusses the nature of genomic information, and the moral arguments
      in support of an individual's right to access it. It analyses the legal avenues
      an individual might take to access their sequence information. The authors
      describe the policy implications in this area and conclude that, for now, the law
      appears to strike an appropriate balance, but new policy will need to be
      developed to address this issue. 

PMID- 24136353
TI  - Long-term cysteine fortification impacts cysteine/glutathione homeostasis and
      food intake in ageing rats.
AB  - PURPOSE: Healthy ageing is associated with higher levels of glutathione. The
      study aimed to determine whether long-term dietary fortification with cysteine
      increases cysteine and glutathione pools, thus alleviating age-associated low
      grade inflammation and resulting in global physiological benefits. METHODS: The
      effect of a 14-week dietary fortification with cysteine was studied in non
      inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade
      inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and
      14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added
      to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI
      rats received a control alanine-supplemented diet. RESULTS: Cysteine
      fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P
      < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification
      increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in
      plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food
      intake decreased over time in alanine-fed rats (r2 = 0.73, P = 0.0002), whereas
      it was constant in cysteine-fed rats (r2 = 0.02, P = 0.68). Cysteine
      fortification did not affect inflammatory markers, mortality, body weight loss,
      or tissue masses. CONCLUSION: Doubling the dietary intake of cysteine in old rats
      increased cysteine and glutathione pools in selected tissues. Additionally, it
      alleviated the age-related decline in food intake. Further validation of these
      effects in the elderly population suffering from age-related anorexia would
      suggest a useful therapeutic approach to the problem.

PMID- 24136354
TI  - Involvement of antioxidant defense system in solvent tolerance of Pseudomonas
      putida BCNU 106.
AB  - The highly solvent-tolerant bacterium Pseudomonas sp. BCNU 106 was investigated
      to elucidate the solvent tolerance under specific culture conditions with the
      presence of solvents and its adaptive mechanisms to those conditions with
      reference to the antioxidant system. When exposed to 10% toluene, Pseudomonas sp.
      BCNU 106 increased the generation of reactive oxygen species assessed by
      monitoring the oxidation of 2',7'-dichlorofluorescein. Typical antioxidant
      enzymes (viz. catalase, superoxide dismutase, and glutathione reductase) showed
      increased activity with prolonged incubation in 10% toluene. In addition, the
      levels of these antioxidant proteins were higher during exposure to 10% toluene
      than in toluene-free condition. The present study indicates that antioxidant
      defense activity is one of the adaptive and protective mechanisms developed to
      avoid the deleterious damage of organic solvents, especially toluene. 

PMID- 24136355
TI  - Coordinated effects of sequence variation on DNA binding, chromatin structure,
      and transcription.
AB  - DNA sequence variation has been associated with quantitative changes in molecular
      phenotypes such as gene expression, but its impact on chromatin states is poorly
      characterized. To understand the interplay between chromatin and genetic control
      of gene regulation, we quantified allelic variability in transcription factor
      binding, histone modifications, and gene expression within humans. We found
      abundant allelic specificity in chromatin and extensive local, short-range, and
      long-range allelic coordination among the studied molecular phenotypes. We
      observed genetic influence on most of these phenotypes, with histone
      modifications exhibiting strong context-dependent behavior. Our results implicate
      transcription factors as primary mediators of sequence-specific regulation of
      gene expression programs, with histone modifications frequently reflecting the
      primary regulatory event. 

PMID- 24136356
TI  - Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory
      infection and airway damage.
AB  - Genetic mutations cause primary immunodeficiencies (PIDs) that predispose to
      infections. Here, we describe activated PI3K-delta syndrome (APDS), a PID
      associated with a dominant gain-of-function mutation in which lysine replaced
      glutamic acid at residue 1021 (E1021K) in the p110delta protein, the catalytic
      subunit of phosphoinositide 3-kinase delta (PI3Kdelta), encoded by the PIK3CD
      gene. We found E1021K in 17 patients from seven unrelated families, but not among
      3346 healthy subjects. APDS was characterized by recurrent respiratory
      infections, progressive airway damage, lymphopenia, increased circulating
      transitional B cells, increased immunoglobulin M, and reduced immunoglobulin G2
      levels in serum and impaired vaccine responses. The E1021K mutation enhanced
      membrane association and kinase activity of p110delta. Patient-derived
      lymphocytes had increased levels of phosphatidylinositol 3,4,5-trisphosphate and
      phosphorylated AKT protein and were prone to activation-induced cell death.
      Selective p110delta inhibitors IC87114 and GS-1101 reduced the activity of the
      mutant enzyme in vitro, which suggested a therapeutic approach for patients with
      APDS. 

PMID- 24136357
TI  - Primate transcript and protein expression levels evolve under compensatory
      selection pressures.
AB  - Changes in gene regulation have likely played an important role in the evolution
      of primates. Differences in messenger RNA (mRNA) expression levels across
      primates have often been documented; however, it is not yet known to what extent
      measurements of divergence in mRNA levels reflect divergence in protein
      expression levels, which are probably more important in determining phenotypic
      differences. We used high-resolution, quantitative mass spectrometry to collect
      protein expression measurements from human, chimpanzee, and rhesus macaque
      lymphoblastoid cell lines and compared them to transcript expression data from
      the same samples. We found dozens of genes with significant expression
      differences between species at the mRNA level yet little or no difference in
      protein expression. Overall, our data suggest that protein expression levels
      evolve under stronger evolutionary constraint than mRNA levels. 

PMID- 24136358
TI  - Extensive variation in chromatin states across humans.
AB  - The majority of disease-associated variants lie outside protein-coding regions,
      suggesting a link between variation in regulatory regions and disease
      predisposition. We studied differences in chromatin states using five histone
      modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of
      diverse ancestry. We found extensive signal variation in regulatory regions,
      which often switch between active and repressed states across individuals.
      Enhancer activity is particularly diverse among individuals, whereas gene
      expression remains relatively stable. Chromatin variability shows genetic
      inheritance in trios, correlates with genetic variation and population
      divergence, and is associated with disruptions of transcription factor binding
      motifs. Overall, our results provide insights into chromatin variation among
      humans. 

PMID- 24136360
TI  - Visualization and quantification of electrochemical and mechanical degradation in
      Li ion batteries.
AB  - High-energy-density materials that undergo conversion and/or alloying reactions
      hold promise for next-generation lithium (Li) ion batteries. However, these
      materials experience substantial volume change during electrochemical operation,
      which causes mechanical fracture of the material and structural disintegration of
      the electrode, leading to capacity loss. In this work, we use x-ray tomography
      during battery operation to visualize and quantify the origins and evolution of
      electrochemical and mechanical degradation. Tomography provides the time
      resolved, three-dimensional chemical composition and morphology within individual
      particles and throughout the electrode. In the model material tin(II) oxide, we
      witness distributions in onset and rate of core-shell lithiation, crack
      initiation and growth along preexisting defects, and irreversible distortion of
      the electrode, highlighting tomography as a tool to guide the development of
      durable materials and strain-tolerant electrodes. 

PMID- 24136359
TI  - Identification of genetic variants that affect histone modifications in human
      cells.
AB  - Histone modifications are important markers of function and chromatin state, yet
      the DNA sequence elements that direct them to specific genomic locations are
      poorly understood. Here, we identify hundreds of quantitative trait loci, genome
      wide, that affect histone modification or RNA polymerase II (Pol II) occupancy in
      Yoruba lymphoblastoid cell lines (LCLs). In many cases, the same variant is
      associated with quantitative changes in multiple histone marks and Pol II, as
      well as in deoxyribonuclease I sensitivity and nucleosome positioning.
      Transcription factor binding site polymorphisms are correlated overall with
      differences in local histone modification, and we identify specific transcription
      factors whose binding leads to histone modification in LCLs. Furthermore,
      variants that affect chromatin at distal regulatory sites frequently also direct
      changes in chromatin and gene expression at associated promoters. 

PMID- 24136361
TI  - New lipid interaction partners stimulate the inhibition of activated protein C by
      cell-penetrating protein C inhibitor.
AB  - Protein C inhibitor (PCI, SerpinA5) is a heparin-binding serpin which can
      penetrate through cellular membranes. Selected negatively charged phospholipids
      like unsaturated phosphatidylserine and oxidised phosphatidylethanolamine bind to
      PCI and stimulate its inhibitory activity towards different proteases. The
      interaction of phospholipids with PCI might also alter the lipid distribution
      pattern of blood cells and influence the remodelling of cellular membranes. Here
      we showed that PCI is an additional binding partner of phosphatidic acid (PA),
      cardiolipin (CL), and phosphoinositides (PIPs). Protein lipid overlay assays
      exhibited a unique binding pattern of PCI towards different lipid species. In
      addition PA, CL, and unsaturated, monophosphorylated PIPs stimulated the
      inhibitory property of PCI towards activated protein C in a heparin like manner.
      As shown for kallistatin (SerpinA4) and vaspin (SerpinA12), the incubation of
      cells with PCI led to the activation of protein kinase B (AKT), which could be
      achieved through direct interaction of PCI with PIPs. This model is supported by
      the fact that PCI stimulated the PIP-dependent 5-phosphatase SHIP2 in vitro,
      which would result in AKT activation. Hence the interaction of PCI with different
      lipids might not only stimulate the inhibition of potential target protease by
      PCI, but could also alter intracellular lipid signalling. 

PMID- 24136362
TI  - Viruses associated with influenza-like-illnesses in Papua New Guinea, 2010.
AB  - Influenza-like-illness can be caused by a wide range of respiratory viruses. The
      etiology of influenza-like-illness in developing countries such as Papua New
      Guinea is poorly understood. The etiological agents associated with influenza
      like-illness were investigated retrospectively for 300 nasopharyngeal swabs
      received by the Papua New Guinea National Influenza Centre in 2010. Real-time
      PCR/RT-PCR methods were used for the detection of 13 respiratory viruses.
      Patients with influenza-like-illness were identified according to the World
      Health Organization case definition: sudden onset of fever (>38 degrees C), with
      cough and/or sore throat, in the absence of other diagnoses. At least one viral
      respiratory pathogen was detected in 66.3% of the samples tested. Rhinoviruses
      (17.0%), influenza A (16.7%), and influenza B (12.7%) were the pathogens detected
      most frequently. Children <5 years of age presented with a significantly higher
      rate of at least one viral pathogen and a significantly higher rate of co
      infections with multiple viruses, when compared to all other patients >5 years of
      age. Influenza B, adenovirus, and respiratory syncytial virus were all detected
      at significantly higher rates in children <5 years of age. This study confirmed
      that multiple respiratory viruses are circulating and contributing to the
      presentation of influenza-like-illness in Papua New Guinea.

PMID- 24136363
TI  - Downstream clinical implications of abnormal myocardial perfusion single-photon
      emission computed tomography based on appropriate use criteria.
AB  - BACKGROUND: Appropriate use criteria (AUC) for single-photon emission computed
      tomography myocardial perfusion images (SPECT-MPI) were developed to address the
      growth of cardiac imaging studies. However, these criteria have not been
      vigorously validated. We sought to determine the rate of abnormal stress SPECT
      MPI studies and subsequent revascularization procedures as categorized by AUC.
      METHODS: We retrospectively examined 280 patients who underwent stress SPECT-MPI
      and categorized these studies as appropriate, inappropriate, or uncertain based
      on AUC. Data regarding subsequent angiography and revascularization within 6
      months after stress SPECT-MPI were collected from the electronic medical record.
      RESULTS: 280 patients met the inclusion criteria (mean age 67.3 +/- 11.4 years,
      36 % female). When categorized by AUC, 62.9 % (N = 176) of stress SPECT-MPI were
      considered appropriate, 13.6 % (N = 38) uncertain, and 23.6 % (N = 66)
      inappropriate. Appropriate stress SPECT-MPI studies were more likely to have
      intermediate or high risk results than uncertain or inappropriate studies [40 %
      (N = 71) vs. 21 % (N = 8) and 18 % (N = 12), respectively; P = 0.008)].
      Appropriate studies were associated with an increased rate of coronary
      angiography [14 % (N = 25)] compared to the uncertain (0 %) and inappropriate [3
      % (N = 2)] studies (P = 0.003). There was also an increased rate of
      revascularization after appropriate studies [9 % (N = 16)] compared to the
      uncertain (0 %) and inappropriate (0 %) studies (P = 0.006). CONCLUSIONS:
      Appropriate stress SPECT-MPI studies are more likely to result in abnormal
      results requiring subsequent revascularization compared to inappropriate and
      uncertain stress studies. Inappropriate and uncertain stress SPECT-MPI did not
      lead to subsequent revascularization.

PMID- 24136364
TI  - Impact of myocardial viability assessed by myocardial perfusion imaging on
      ventricular tachyarrhythmias in cardiac resynchronization therapy.
AB  - BACKGROUND: The presence of myocardial fibrosis is associated with ventricular
      tachyarrhythmia (VT) occurrence irrespective of cardiomyopathy etiology. The aim
      of our study was to evaluate the impact of global and regional viability on VTs
      in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Fifty
      seven patients with advanced heart failure (age 62.3 +/- 10.2; 38 men; 24
      ischemic etiology) were evaluated using single-photon emission computed
      tomography myocardial perfusion imaging before CRT defibrillator device
      implantation. Global myocardial viability was determined by the number of viable
      segments in a 20-segment model. Regional viability was calculated as the mean
      tracer activity in the corresponding segments at left ventricular (LV) lead
      position. LV lead segments were determined at implant venography using 2
      projections (left anterior oblique 30 and right anterior oblique 30) of coronary
      sinus tributaries. Patients were followed 30 (24-34) months for the occurrence of
      VTs. RESULTS: VTs were registered in 18 patients (31.6%). Patients without VTs
      had significantly more viable segments (17.6 +/- 2.35 vs 14.2 +/- 4.0; P = .002)
      and higher regional myocardial viability at LV lead position (66.1% +/- 10.3% vs
      54.8% +/- 11.4% of tracer activity; P = .001) than those with VTs. In
      multivariate logistic regression models, the number of viable segments (OR =
      0.66; 95% confidence interval (CI) 0.53-0.85; P = .001) and regional viability
      (OR = 0.90; 95% CI 0.85-0.97; P = .003) were the only independent predictors of
      VT occurrence. CONCLUSION: Global and regional myocardial viability are
      independently related to the occurrence of VTs in patients after CRT.

PMID- 24136365
TI  - Induction of mucosal immunity and protection by intranasal immunization with a
      respiratory syncytial virus subunit vaccine formulation.
AB  - The majority of infections, including those caused by respiratory syncytial virus
      (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to
      produce an effective subunit vaccine with an adjuvant suitable for mucosal
      delivery and cross-presentation. A truncated secreted version of the RSV fusion
      (DeltaF) protein formulated with polyI : C, an innate defence regulator peptide
      and polyphosphazene, induced local and systemic immunity, including affinity
      maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F
      specific CD8(+) T-cells in the lung, when delivered intranasally. Furthermore,
      this DeltaF protein formulation promoted the production of CD8(+) central memory
      T-cells in the mediastinal lymph nodes and provided protection from RSV
      challenge. Formulation of DeltaF protein with this adjuvant combination enhanced
      uptake by lung dendritic cells and trafficking to the draining lymph nodes. The
      DeltaF protein formulation was confirmed to be highly efficacious and safe in
      cotton rats. 

PMID- 24136367
TI  - An unconventional TRAIL to cancer therapy.
AB  - Cellular immunotherapy offers novel, safe, and effective routes to treating
      cancer. However, approaches utilizing cytotoxic CD8(+) T cells are hampered by
      the need to identify suitable target antigens that are expressed by tumor cells
      but not healthy tissues, and that are recognized with sufficient affinity. Most
      importantly, the applicability of CD8(+) T-cell-based therapies is governed by
      the MHC restriction of tumor-specific epitopes, thereby limiting the potential
      benefit to patients carrying the appropriate MHC haplotype. Alternative
      approaches to harness the immune system against tumors exploit non-MHC-restricted
      gammadelta T cells that recognize stress-induced changes in transformed cells. A
      new report in this issue of the European Journal of Immunology [Eur. J. Immunol.
      2013. 43: 3175-3182] shows that human gammadelta T cells efficiently kill lung
      cancer cells through recognition of the NKG2D ligand ULBP2 and secretion of
      soluble TRAIL. This finding provides new evidence for a TCR-independent
      cytotoxicity of gammadelta T cells and supports their promising potential for non
      MHC-restricted immunotherapies. 

PMID- 24136366
TI  - The adenovirus 55 residue E1A protein is a transcriptional activator and binds
      the unliganded thyroid hormone receptor.
AB  - The early region 1A (E1A) of human adenovirus types 2 and 5 is differentially
      spliced to yield five distinct mRNAs that encode different proteins. The smallest
      E1A RNA transcript encodes a 55 residue (55R) protein that shares only 28 amino
      acid residues with the other E1A proteins. Even though it is the most abundant
      E1A transcript at late times post-infection, little is known about the functions
      of this E1A isoform. In this study, we show that the E1A 55R protein interacts
      with, and modulates the activity of the unliganded thyroid hormone receptor (TR).
      We demonstrate that E1A 55R contains a signature motif known as the CoRNR box
      that confers interaction with the unliganded TR; this motif was originally
      identified in cellular corepressors. Using a system reconstituted in the yeast
      Saccharomyces cerevisiae, which lack endogenous TR and TR coregulators, we show
      that E1A 55R nonetheless differs from cellular corepressors as it functions as a
      strong co-activator of TR-dependent transcription and that it possesses an
      intrinsic transcriptional activation domain. These data indicate that the E1A 55R
      protein functions as a transcriptional regulator. 

PMID- 24136368
TI  - Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of
      bacterial meningitis in Malawian children.
AB  - We investigated the benefit of 2 candidate adjunctive therapies in bacterial
      meningitis: glycerol, which has shown promise in earlier studies, and
      acetaminophen, which is reportedly beneficial in adult septicemia. In a hospital
      in Blantyre, Malawi, we enrolled 360 children aged >= 2 months with proven
      bacterial meningitis (36% HIV infected) in a double-blind, randomized, placebo
      controlled trial of glycerol and acetaminophen in a 2 * 2 factorial design. Of 4
      groups, first group received oral glycerol, second received rectal acetaminophen,
      third received both therapies and the fourth received placebos only. Adjuvant
      therapies were given for the first 48 hours of antibiotic therapy. Endpoints were
      mortality and neurological sequelae. Baseline findings were similar across all
      groups, except that many children had prior antibiotics in the acetaminophen
      group and many were anemic in the acetaminophen and glycerol group. Outcomes were
      similar for all groups. We found no benefit from oral glycerol or rectal
      acetaminophen in, mostly pneumococcal, meningitis in Malawian children. 

PMID- 24136369
TI  - 13-Valent pneumococcal conjugate vaccine in older children and adolescents either
      previously immunized with or naive to 7-valent pneumococcal conjugate vaccine.
AB  - BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been
      demonstrated to be immunogenic and safe for administration to infants and
      children aged <5 years. PCV13 recently was approved for children and adolescents
      aged up to 17 years as the vaccine may be of benefit to some in this older age
      group. METHODS: In this open-label study, healthy children aged >=5 to <10 years
      (ie, the younger age group) previously vaccinated (>=1 dose) with 7-valent PCV
      (PCV7) and pneumococcal vaccine-naive children aged >=10 to <18 years (ie, the
      older age group) received 1 dose of PCV13. For the younger group,
      antipneumococcal immunoglobulin (Ig) G geometric mean concentrations 1 month
      postvaccination were compared with posttoddler dose (PCV13 or PCV7) levels from a
      historical control study. Opsonophagocytic activity geometric mean titers 1 month
      postvaccination for the older group were compared with the younger age group.
      Safety data were collected. RESULTS: Five hundred and ninety-eight children were
      enrolled, 299 in each age group. For PCV7 serotypes, IgG geometric mean
      concentrations in the younger group were 8.23-53.56 MUg/mL, >=2.5-fold greater
      than historical posttoddler dose values. For the 6 additional serotypes, IgG
      geometric mean concentrations in the younger group were 2.38-21.51 MUg/mL, >=1.2
      fold greater than historical posttoddler dose values. Opsonophagocytic activity
      geometric mean titers were similar in the older and younger age groups, except
      for serotype 3 which was lower in the older group. Safety was comparable in both
      groups. CONCLUSIONS: PCV13 was immunogenic and safe when administered to older
      children and adolescents, regardless of prior PCV7 vaccination.

PMID- 24136370
TI  - Rotavirus antigenemia in children is associated with more severe clinical
      manifestations of acute gastroenteritis.
AB  - BACKGROUND: Rotavirus (RV) antigenemia and RNAemia are common findings in
      rotavirus-infected children. Sporadic associations between RV antigenemia and
      extraintestinal manifestations of RV infection have been observed. We examined
      the clinical severity of RV gastroenteritis in patients with and without RV
      antigenemia or RNAemia. METHODS: Stool, serum and whole blood samples were
      collected from children seen with acute gastroenteritis in Tampere University
      Hospital and studied for RV using reverse transcription polymerase chain reaction
      and enzyme-linked immunosorbent assay. Only exclusively RV-positive specimens
      were included into this study. The patients were divided into groups according to
      RV findings from stool, serum and blood specimens. Clinical manifestations were
      graded according to 20-point Vesikari scoring system. RESULTS: Of 374 children,
      155 (41%) had RV in their stools. Of these 155 children, 105 (67%) were found to
      have RV RNA in the serum; of those, 94 (90%) had also RV enzyme-linked
      immunosorbent assay antigen. Thus antigenemia occurred in 61% (94 cases) of RV
      infected children all of whom had concomitant RNAemia. Neither antigenemia nor
      RNAemia were detected in 85 patients with non-RV gastroenteritis. Patients who
      had RV RNA and RV antigen in both serum and stools were more likely to have a
      higher level of fever and more severe vomiting than patients who had RV only in
      stools. G1 genogroup RV was more often associated with RNAemia and antigenemia
      than other genogroups combined. CONCLUSION: Rotavirus antigenemia and viremia are
      commonly detected in children hospitalized for RV gastroenteritis and may be
      associated with increased severity of fever and vomiting.

PMID- 24136371
TI  - Role of management strategies in reducing mortality from invasive fungal disease
      in children with cancer or receiving hemopoietic stem cell transplant: a single
      center 30-year experience.
AB  - BACKGROUND: In the last decades, several diagnostic and therapeutic strategies
      have been implemented for management of invasive fungal diseases (IFD) in
      patients with cancer or receiving allogeneic hemopoietic stem cell transplant.
      Few data are available on their impact on mortality in children. METHODS: All IFD
      episodes diagnosed at tertiary care center during a 30-year period between 1983
      and 2012 were analyzed for 90-day mortality and risk factors. Diagnoses were
      coded according to international (European Organization for Research and
      Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National
      Institute of Allergy and Infectious Diseases Mycoses Study Group) criteria. Four
      treatment eras (1983-1990, 1991-1999, 2000-2005 and 2006-2012) were defined
      according to availability of diagnostic technologies, new antifungal drugs and
      use of a diagnostic-driven approach without empiric antifungal therapy. RESULTS:
      A total of 198 IFD were diagnosed in 191 patients; 71.2% were proven/probable
      infections; 39.9% were caused by yeasts and 31.3% by molds. Within 90 days from
      IFD diagnosis, 58 (30.4%) patients died for a 28.3% cumulative probability of
      death. A multivariable analysis showed that the highest risk of death was
      associated with alternative donor-hemopoietic stem cell transplant [hazard ratio
      (HR): 3.96] and mold etiology (HR: 1.34). The risk of death significantly
      decreased across the treatment eras, with almost a 3-fold reduced risk for
      patients diagnosed during the 2006-2012 period (HR: 0.24). Also if the variable
      year of diagnosis was considered as continuous, the hazard of death significantly
      decreased by 5% per year (HR: 0.95). CONCLUSIONS: New management strategies
      resulted in a better prognosis of IFD in children with cancer or hemopoietic stem
      cell transplant. A diagnostic-driven approach was not associated with an increase
      in mortality.

PMID- 24136372
TI  - Varicella outbreak in a daycare: challenges and opportunities for preventing
      varicella outbreaks in this setting.
AB  - As a result of single-dose varicella vaccination, daycare outbreaks have become
      rare. We investigated a daycare outbreak resulting from a misdiagnosed varicella
      case in an unvaccinated attendee. Of 25 attendees aged 12-32 months without
      evidence of immunity, 7 (28%) were unvaccinated due to religious/philosophical
      opposition or recent 1st birthday. Single-dose vaccination reduced disease by 92%
      compared with no vaccination. 

PMID- 24136373
TI  - Impact of varicella vaccination on varicella-related hospitalizations among
      American Indian/Alaska Native people.
AB  - BACKGROUND: Routine childhood varicella vaccination, implemented in 1995, has
      resulted in significant declines in varicella-related hospitalizations in the
      United States. Varicella hospitalization rates among the American Indian (AI) and
      Alaska Native (AN) population have not been previously documented. METHODS: We
      selected varicella-related hospitalizations, based on a published definition,
      from the Indian Health Service inpatient database for AI/ANs in the Alaska,
      Southwest and Northern Plains regions (1995-2010) and from the Nationwide
      Inpatient Sample for the general US population (2007-2010). We analyzed average
      annual hospitalization rates prevaccine (1995-1998) and postvaccine (2007-2010)
      for the AI/AN population, and postvaccine for the general US population. RESULTS:
      From 1995-1998 to 2007-2010, the average annual varicella-related hospitalization
      rate for AI/ANs in the 3 regions decreased 95% (0.66-0.03/10,000 persons); the
      postvaccine rate appears lower than the general US rate (0.06, 95% confidence
      interval: 0.05-0.06). The rate declined in all AI/AN pediatric age groups.
      Infants experienced the highest prevaccine (14.07) and postvaccine (0.83)
      hospitalization rates. Adults experienced low rates in both periods. Varicella
      vaccination rates in 19- to 35-month-old AI/AN children during fiscal years 2008
      2010 were 88.1-91.0%. CONCLUSIONS: Widespread use of varicella vaccine in AI/AN
      children was accompanied by substantial declines in varicella-related
      hospitalizations consistent with high varicella vaccine effectiveness in
      preventing severe varicella outcomes.

PMID- 24136374
TI  - Nickel tolerance of serpentine and non-serpentine Knautia arvensis plants as
      affected by arbuscular mycorrhizal symbiosis.
AB  - Serpentine soils have naturally elevated concentrations of certain heavy metals,
      including nickel. This study addressed the role of plant origin (serpentine vs.
      non-serpentine) and symbiosis with arbuscular mycorrhizal fungi (AMF) in plant Ni
      tolerance. A semi-hydroponic experiment involving three levels of Ni and
      serpentine and non-serpentine AMF isolates and populations of a model plant
      species (Knautia arvensis) revealed considerable negative effects of elevated Ni
      availability on both plant and fungal performance. Plant growth response to Ni
      was independent of edaphic origin; however, higher Ni tolerance of serpentine
      plants was indicated by a smaller decline in the concentrations of photosynthetic
      pigments and restricted root-to-shoot Ni translocation. Serpentine plants also
      retained relatively more Mg in their roots, resulting in a higher shoot Ca/Mg
      ratio. AMF inoculation, especially with the non-serpentine isolate, further
      aggravated Ni toxicity to host plants. Therefore, AMF do not appear to be
      involved in Ni tolerance of serpentine K. arvensis plants. 

PMID- 24136375
TI  - A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered
      endothelial function in adults with sickle cell anemia.
AB  - GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4)
      synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic
      hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain,
      but have not been investigated in African populations. We examined GCH1 and pain
      in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in
      discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR
      2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects
      homozygous for the risk allele produced higher BH4. In vivo physiological studies
      of traits likely to be modulated by GCH1 showed rs8007267 is associated with
      altered endothelial dependent blood flow in females with SCA (8.42% of variation;
      P = 0.002). The GCH1 pain association is attributable to an African haplotype
      with where its sickle cell anemia pain association is limited to females (OR
      2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association
      described in Europeans independent of global admixture. The presence of a GCH1
      haplotype with high BH4 in populations of African ancestry could explain the
      association of rs8007267 with sickle cell anemia pain crises. The vascular
      effects of GCH1 and BH4 may also have broader implications for cardiovascular
      disease in populations of African ancestry.

PMID- 24136376
TI  - Trajectories of substance use among young American Indian adolescents: patterns
      and predictors.
AB  - Substance use often begins earlier among American Indians compared to the rest of
      the United States, a troubling reality that puts Native youth at risk for
      escalating and problematic use. We need to understand more fully patterns of
      emergent substance use among young American Indian adolescents, risk factors
      associated with escalating use trajectories, and protective factors that can be
      parlayed into robust prevention strategies. We used growth mixture modeling with
      longitudinal data from middle-school students on a Northern Plains reservation
      (Wave 1 N = 381, M age at baseline = 12.77, 45.6% female) to identify subgroups
      exhibiting different trajectories of cigarette, alcohol, and marijuana use. We
      explored how both risk (e.g., exposure to stressful events, deviant peers) and
      protective (e.g., positive parent-child relationships, cultural identity) factors
      were related to these trajectories. For all substances, most youth showed
      trajectories characterized by low rates of substance use (nonuser classes), but
      many also showed patterns characterized by high and/or escalating use. Across
      substances, exposure to stress, early puberty, and deviant peer relationships
      were associated with the more problematic patterns, while strong relationships
      with parents and prosocial peers were associated with nonuser classes. Our
      measures of emergent cultural identity were generally unrelated to substance use
      trajectory classes among these young adolescents. The findings point to the
      importance of early substance use prevention programs for American Indian youth
      that attenuate the impact of exposure to stressful events, redirect peer
      relationships, and foster positive parent influences. They also point to the need
      to explore more fully how cultural influences can be captured.

PMID- 24136377
TI  - Does humor explain why relationally aggressive adolescents are popular?
AB  - The association between relational aggression and popularity during early
      adolescence is well established. Yet, little is known about why, exactly,
      relationally aggressive young adolescents are able to achieve and maintain high
      popular status among peers. The present study investigated the mediating role of
      humor in the association between relational aggression and popularity during
      early adolescence. Also considered was whether the association between relational
      aggression and humor varies according to adolescents' gender and their friends'
      levels of relational aggression. Participants were 265 sixth-grade students (48%
      female; 41% racial/ethnic minority; M age = 12.04 years) who completed peer
      nomination and friendship measures in their classrooms at two time points (Wave
      1: February; Wave 2: May). The results indicated that Wave 1 relational
      aggression was related to Wave 1 and 2 popularity indirectly through Wave 1
      humor, after accounting for the effects of Wave 1 physical aggression, ethnicity,
      and gender. Additional analyses showed that relational aggression and humor were
      related significantly only for boys and for young adolescents with highly
      relationally aggressive friends. The results support the need for further
      research on humor and aggression during early adolescence and other mechanisms by
      which relationally aggressive youth achieve high popular status.

PMID- 24136378
TI  - Influence of high-dose intraoperative remifentanil with or without amantadine on
      postoperative pain intensity and morphine consumption in major abdominal surgery
      patients: a randomised trial.
AB  - BACKGROUND: Human volunteer studies demonstrate ketamine-reversible opioid
      induced hyperalgesia, consistent with reports of increased postoperative pain and
      analgesic consumption. However, recent clinical trials showed controversial
      results after intraoperative administration of high-dose remifentanil. OBJECTIVE:
      To investigate in lower abdominal surgery patients whether postoperative pain
      intensity and analgesic consumption are increased following intraoperative high
      dose vs. low-dose remifentanil, and whether this could be prevented by
      preoperative administration of the NMDA antagonist amantadine. DESIGN:
      Randomised, placebo-controlled, clinical study. SETTING: University hospital.
      PATIENTS: Sixty patients scheduled for elective major lower abdominal surgery.
      INTERVENTIONS: Patients were randomly assigned to one of three anaesthetic
      regimens. First, in the group 'low-dose remifentanil and preoperative isotonic
      saline' (n=15), a remifentanil infusion was maintained at a rate of 0.1 MUg kg
      min throughout anaesthesia, and the end-tidal concentration of sevoflurane
      started at 0.5 minimum alveolar concentration (MAC) and was increased by 0.2%
      increments according to clinical demand. Preoperatively, 500 ml NaCl 0.9% were
      infused as study solution. Second, in the group 'high-dose remifentanil and
      preoperative saline' (n=17), the end-tidal concentration of sevoflurane was
      maintained at 0.5 MAC throughout anaesthesia. A remifentanil infusion was started
      at a rate of 0.2 MUg kg min and subsequently increased by 0.05 MUg kg min
      increments to clinical demand. Preoperatively, these patients also received a
      solution of 500 ml NaCl 0.9% as study solution. Third, the group 'high-dose
      remifentanil and preoperative amantadine' (n=16) received the same anaesthetic
      protocol as the second group, but the preoperative study solution was substituted
      by amantadine (200 mg/500 ml). MAIN OUTCOME MEASURES: Pain intensity measured by
      the numerical rating scale and cumulative morphine consumption. RESULTS: The
      remifentanil dose in both high-dose groups was significantly higher compared with
      the low-dose remifentanil group (0.20+/-0.04 and 0.23+/-0.02 vs. 0.08+/-0.04 MUg
      kg min; P<0.001). Pain intensity gradually increased up to 45 min postoperatively
      in all groups, and then decreased again towards low levels in parallel with a
      linear increase in morphine consumption. Postoperative pain intensity and
      morphine consumption did not significantly differ between groups. Moreover,
      preoperative amantadine revealed no additional benefit. CONCLUSION: We were not
      able to demonstrate any influence on routine clinical outcome parameters of pain
      after high-dose remifentanil. Although not without limitations, these findings
      are in line with other clinical trials that could not detect an opioid-induced
      impact on postoperative pain parameters, which might be less sensitive to detect
      opioid-induced hyperalgesia compared with quantitative sensory testing. TRIAL
      REGISTRATION: DRKS00004626.

PMID- 24136379
TI  - Dexamethasone decreases the duration of rocuronium-induced neuromuscular block: a
      randomised controlled study.
AB  - BACKGROUND: Several drugs influence the time course of neuromuscular block during
      general anaesthesia. OBJECTIVE: To evaluate the effect of a single dose of
      dexamethasone 8 mg on the time course of a rocuronium-induced neuromuscular
      block. DESIGN: A randomised controlled, unblinded, monocentre trial. SETTING:
      Kreiskrankenhaus Dormagen, Dormagen, Germany. PATIENTS: One hundred and eight
      adult patients scheduled for elective gynaecological laparoscopic surgery
      allocated to three groups. INTERVENTIONS: Patients received dexamethasone 8 mg
      intravenously 2 to 3 h prior to surgery (Group A), during induction of
      anaesthesia (Group B) or after recovery of the neuromuscular block (Group C,
      control). MAIN OUTCOME MEASURES: The time course of the neuromuscular block of
      rocuronium 0.3 mg kg was assessed using acceleromyography. The primary end point
      was the time from start of injection of rocuronium until recovery to a train-of
      four ratio of 0.9. RESULTS: The clinical duration was decreased in Group A (15.8
      +/- 4.5 min) compared with Group B (18.7 +/- 5.8 min; P = 0.031). The recovery
      index was reduced in Group A (6.8 +/- 1.8 min) compared with Group B (8.1 +/- 2.6
      min; P = 0.018) and Group C (8.3 +/- 2.8 min; P = 0.01). The recovery to a train
      of-four ratio of 0.9 was shorter in Group A (30.4 +/- 6.9 min) than in Groups B
      (36.3 +/- 10.7 min; P = 0.031) and C (36.8 +/- 11.3 min; P = 0.02). CONCLUSION: A
      single dose of dexamethasone 8 mg attenuated rocuronium-induced block by 15 to
      20% if administered 2 to 3 h prior to induction of anaesthesia. However, the
      administration of dexamethasone during induction of anaesthesia did not influence
      the time course of the neuromuscular block. TRIAL REGISTRATION: ClinicalTrial.gov
      Identifier: NCT01782820.

PMID- 24136380
TI  - Do not know where to press? Cricoid pressure in the very young.

PMID- 24136381
TI  - Clinical implementation of germ line cancer pharmacogenetic variants during the
      next-generation sequencing era.
AB  - More than 100 medications approved by the US Food and Drug Administration include
      pharmacogenetic biomarkers in the drug label, many with cancer indications
      referencing germ line DNA variations. With the advent of next-generation
      sequencing (NGS) and its rapidly increasing uptake into cancer research and
      clinical practice, an enormous amount of data to inform documented gene-drug
      associations will be collected that must be exploited to optimize patient
      benefit. This review focuses on the implementation of germ line cancer
      pharmacogenetics in clinical practice. Specifically, it discusses the importance
      of germ line variation in cancer and the role of NGS in pharmacogenetic discovery
      and implementation. In the context of a scenario in which massive amounts of NGS
      based genetic information will be increasingly available to health stakeholders,
      this review explores the ongoing debate regarding the threshold of evidence
      necessary for implementation, provides an overview of recommendations in cancer
      by professional organizations and regulatory bodies, and discusses limitations of
      current guidelines and strategies to improve third-party coverage. 

PMID- 24136382
TI  - Isolation of Salmonella Virchow from a fruit bat (Pteropus giganteus).
AB  - Detection of zoonotic pathogens carried by bats is important both for
      understanding disease ecology and for developing preventive measures. Pteropus
      fruit bats have been identified as potential carriers of Salmonella enterica
      serotype Typhi. A cross-sectional study was conducted to determine the prevalence
      of Salmonella Typhi and other Salmonella serotypes in Pteropus giganteus fruit
      bats in Bangladesh. Rectal swabs were collected from 302 bats and cultured for
      Salmonella species. The bats were trapped in three districts (Faridpur, Rajbari,
      and Cox's Bazar). Salmonella Typhi was not found but one juvenile female bat from
      Faridpur district was positive for Salmonella Virchow. Close associations between
      frugivorous bats, humans, and livestock in rural Bangladesh make it likely that
      the bat was infected by consuming contaminated water. 

PMID- 24136383
TI  - Impact of avian influenza on village poultry production globally.
AB  - Village poultry and their owners were frequently implicated in disease
      transmission in the early days of the highly pathogenic avian influenza (HPAI)
      H5N1 pandemic. With improved understanding of the epidemiology of the disease, it
      was recognized that village poultry raised under extensive conditions pose less
      of a threat than intensively raised poultry of homogeneous genetic stock with
      poor biosecurity. This paper provides an overview of village poultry production
      and the multiple ways that the HPAI H5N1 pandemic has impacted on village
      poultry, their owners, and the traders whose livelihoods are intimately linked to
      these birds. It reviews impact in terms of gender and cultural issues; food
      security; village poultry value chains; approaches to biosecurity; marketing;
      poultry disease prevention and control; compensation; genetic diversity; poultry
      as part of livelihood strategies; and effective communication. It concludes on a
      positive note that there is growing awareness amongst animal health providers of
      the importance of facilitating culturally sensitive dialogue to develop HPAI
      prevention and control options. 

PMID- 24136384
TI  - Causes of morbidity and mortality in free-living birds in an urban environment in
      Germany.
AB  - Free-living birds are often presented to veterinarians at rehabilitation centers
      as well as in private practice. Information about disease processes and causes of
      death of indigenous free-living birds can aid the clinician in establishing
      proper treatment and in the assessment of potential zoonotic risks. For the
      present study, pathogens as causes of morbidity and mortality were determined by
      performing a complete necropsy on free-living birds presented to the Clinic for
      Birds and Reptiles of the University of Leipzig (Germany) that died shortly after
      admission or were euthanized due to an unfavorable prognosis. Over a 2-year
      period, 251 birds representing 13 families (Accipitridae, Apodidae, Columbidae,
      Corvidae, Falconidae, Fringillidae, Hirundinidae, Paridae, Passeridae, Picidae,
      Strigidae, Sturnidae and Turdidae) were examined. Trauma (62%), including several
      bite injuries inducing bacterial septicemia caused by Pasteurella multocida, was
      the most common cause of morbidity. Parasitic disease (18%) was mainly caused by
      Trichomonas gallinae, Eucoleus dispar and Syngamus trachea. Metabolic disease
      (13%), including fibrous osteodystrophy, was almost exclusively limited to
      juvenile specimens. Different Enterobacteriaceae including E. coli, Salmonella
      Typhimurium DT040 as well as Mycobacterium avium ssp. avium were identified as
      causal agents of primary bacterial disease (5%). Primary bacterial infection as
      cause of death or disease was of major importance in nestlings. Viral infections,
      mycoses and intoxication had minor significance as causes of morbidity. 

PMID- 24136385
TI  - Environmental health education in schools as strategy for rodent control: an
      experience in a shantytown of Buenos Aires, Argentina.
AB  - The general aim of this study was to assess the possibility of including elements
      of environmental health education within the curriculum of a school located in a
      shantytown of Buenos Aires city, Argentina. An environmental health education
      campaign was designed to introduce school-aged children to the problems posed by
      the lack of environmental sanitation, by using rodents as indicators of
      environmental disorder. The methodology implemented consisted of a lecture and
      two practical activities where the participating children were the evaluators of
      their neighborhood environment, recording the environmental factors that indicate
      direct or indirect presence of rodents and carrying out a survey about rodents
      among their neighbors. To assess the impact of the activities, an anonymous
      questionnaire was performed with the students before and after the campaign. The
      results showed that students were able to identify the man-made factors which
      favor the presence of rodents and were encouraged to propose strategies related
      to environmental sanitation to reduce rodent proliferation and the transmission
      of their parasites. This study demonstrated the feasibility of performing
      environmental health education campaigns in school-aged children by using
      practical activities to stimulate observation, participation, and comprehensive
      understanding of the problems posed by urban pests. 

PMID- 24136386
TI  - Has the time come for big science in wildlife health?
AB  - The consequences of wildlife emerging diseases are global and profound with
      increased burden on the public health system, negative impacts on the global
      economy, declines and extinctions of wildlife species, and subsequent loss of
      ecological integrity. Examples of health threats to wildlife include
      Batrachochytrium dendrobatidis, which causes a cutaneous fungal infection of
      amphibians and is linked to declines of amphibians globally; and the recently
      discovered Pseudogymnoascus (Geomyces) destructans, the etiologic agent of white
      nose syndrome which has caused precipitous declines of North American bat
      species. Of particular concern are the novel pathogens that have emerged as they
      are particularly devastating and challenging to manage. A big science approach to
      wildlife health research is needed if we are to make significant and enduring
      progress in managing these diseases. The advent of new analytical models and
      bench assays will provide us with the mathematical and molecular tools to
      identify and anticipate threats to wildlife, and understand the ecology and
      epidemiology of these diseases. Specifically, new molecular diagnostic techniques
      have opened up avenues for pathogen discovery, and the application of spatially
      referenced databases allows for risk assessments that can assist in targeting
      surveillance. Long-term, systematic collection of data for wildlife health and
      integration with other datasets is also essential. Multidisciplinary research
      programs should be expanded to increase our understanding of the drivers of
      emerging diseases and allow for the development of better disease prevention and
      management tools, such as vaccines. Finally, we need to create a National Fish
      and Wildlife Health Network that provides the operational framework (governance,
      policies, procedures, etc.) by which entities with a stake in wildlife health
      cooperate and collaborate to achieve optimal outcomes for human, animal, and
      ecosystem health. 

PMID- 24136387
TI  - Introgression in Lake Malawi: increasing the threat of human urogenital
      schistosomiasis?
AB  - For the last 15 years, we have studied the relationships among cichlid snail
      eating fishes, intermediate snail-host density, and the prevalence of human
      infection of Schistosoma haematobium in Lake Malawi and concluded that the
      increase of human infection is correlated with the decrease in snail-eating
      fishes in the shallow waters of the lake. We postulated that a strain of S.
      haematobium from other parts of Africa, which was introduced into the Cape
      Maclear region of Lake Malawi by tourists, was compatible with Bulinus nyassanus
      which is a close relative of B. truncatus, and interbred with the indigenous
      strain of S. haematobium, which ultimately produced via introgression a strain
      that can use both B. globosus and B. nyassanus as intermediate hosts. This
      actively evolving situation involving intermediate snail-host switching and
      decline of Trematocranus placodon, a natural cichlid snail predator, will impact
      on transmission of urogenital schistosomiasis within the local communities and on
      tourists who visit Lake Malawi. 

PMID- 24136388
TI  - Indoor Air Pollution and Health in Ghana: Self-Reported Exposure to Unprocessed
      Solid Fuel Smoke.
AB  - Most countries in Sub-Saharan Africa including Ghana still depend extensively on
      unprocessed solid cooking fuels with many people exposed on a daily basis to
      harmful emissions and other health risks. In this study, using complementary log
      log multivariate models, we estimated the health effects of exposure to smoke
      from unprocessed wood in four regions of Ghana while controlling for socio
      environmental and socio-demographic factors. The results show that the
      distribution of self-reported exposure to smoke was highest among participants in
      the Northern region, rural dwellers, the 25-49 age groups, individuals with no
      education, and married women. As expected, exposure to smoke was higher in
      crowded households and in communities without basic social amenities. Region,
      residential locality, housing quality (type of roofing, floor and exterior
      materials), self-reported housing condition, and access to toilet facilities were
      associated with self-reported exposure to solid fuel smoke. Participants living
      in urban areas were less likely (OR = 0.82, rho <= 0.01) to be exposed to solid
      fuel smoke compared to their rural counterparts. An inverse relationship between
      self-reported housing condition and exposure to solid fuel smoke was observed and
      persisted even after adjustments were made for confounding variables in the
      demographic model. In Ghana, the cost and intermittent shortages of liquefied
      petroleum gas and other alternative fuel sources hold implications for the
      willingness of the poor to shift to their use. Thus, the poorest rural
      populations with nearly no cash income and electricity, but with access to wood
      and/or agricultural waste, are unlikely to move to clean fuels or use
      significantly improved stoves without large subsidies, which are usually not
      sustainable. However, there appears to be large populations between these
      extremes that can be targeted by efforts to introduce improved stoves. 

PMID- 24136389
TI  - Therapeutic plasma exchange in neuromyelitis optica: a case series.
AB  - Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central
      nervous system that predominantly affects the spinal cord and optic nerves. The
      clinical hallmark of the disease is a step-wise deterioration of visual and
      spinal cord function. This study reviews patients with steroid resistant
      relapsing NMO presenting for therapeutic plasma exchange (TPE) at our institution
      from December 2005 to December 2012. A total of five patients were treated with
      single volume TPE. Both subjective and objective clinical response to TPE was
      estimated by three different sources (the patient, a Transfusion Medicine
      physician, and the treating Neurologist) with the patient and Transfusion
      Medicine physician's final assessment of response made at the time of the last
      TPE in the series and the treating neurologist's assessment of response made at
      the time of the next neurological exam after the last TPE. A total of 17 TPE
      series were performed with the average course of therapy being three series
      (ranged 1-5) with five TPE (ranged 3-7) per series. All patients demonstrated
      improvement with each series of TPE and all procedures were well tolerated with
      only transient and well-described reactions all of which were successfully
      resolved with minor or no sequelae.

PMID- 24136390
TI  - Differences in transport mechanisms of trans-1-amino-3
      [18F]fluorocyclobutanecarboxylic acid in inflammation, prostate cancer, and
      glioma cells: comparison with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro
      D-glucose.
AB  - PURPOSE: We aimed to elucidate trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic
      acid (anti-[(18)F]FACBC) uptake mechanisms in inflammatory and tumor cells, in
      comparison with those of L-[methyl-(11)C]methionine ([(11)C]Met) and 2-deoxy-2
      [(18)F]fluoro-D-glucose ([(18)F]FDG). PROCEDURES: Using carbon-14-labeled
      tracers, in vitro time-course, pH dependence, and competitive inhibition uptake
      experiments were performed in rat inflammatory (T cells, B cells, granulocytes,
      macrophages), prostate cancer (MLLB2), and glioma (C6) cells. RESULTS: Anti
      [(14)C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while
      those of granulocytes/macrophages to tumor cells were lower than those for
      [(14)C]FDG. Over half of anti-[(14)C]FACBC uptake by T/B and tumor cells was
      mediated by Na(+)-dependent amino acid transporters (system ASC), whereas most
      [(14)C]Met transport in all cells was mediated by Na(+)-independent carriers
      (system L). CONCLUSIONS: The low anti-[(18)F]FACBC accumulation in
      granulocytes/macrophages may be advantageous in discriminating inflamed regions
      from tumors. The significant anti-[(18)F]FACBC uptake in T/B cells may cause
      false-positives in some cancer patients who undergo FACBC-positron emission
      tomography (PET).

PMID- 24136391
TI  - Stereoselective synthesis of (-)-lepadins A-C.
AB  - A concise synthesis of the marine alkaloids (-)-lepadins A-C from a
      phenylglycinol-derived tricyclic lactam is reported. Key steps from the
      stereochemical standpoint involve stereoselective cyclocondensation, double bond
      hydrogenation, oxazolidine opening, hydroboration-oxidation, and Horner-Wadsworth
      Emmons reactions. 

PMID- 24136392
TI  - MnSODtg mice control myocardial inflammatory and oxidative stress and remodeling
      responses elicited in chronic Chagas disease.
AB  - BACKGROUND: We utilized genetically modified mice equipped with a variable
      capacity to scavenge mitochondrial and cellular reactive oxygen species to
      investigate the pathological significance of oxidative stress in Chagas disease.
      METHODS AND RESULTS: C57BL/6 mice (wild type, MnSODtg, MnSOD+/-, GPx1-/-) were
      infected with Trypanosoma cruzi and harvested during the chronic disease phase.
      Chronically infected mice exhibited a substantial increase in plasma levels of
      inflammatory markers (nitric oxide, myeloperoxidase), lactate dehydrogenase, and
      myocardial levels of inflammatory infiltrate and oxidative adducts
      (malondialdehyde, carbonyls, 3-nitrotyrosine) in the order of wild type = MnSOD+/
      > GPx1-/- > MnSODtg. Myocardial mitochondrial damage was pronounced and
      associated with a > 50% decline in mitochondrial DNA content in chronically
      infected wild-type and GPx1(-/-) mice. Imaging of intact heart for cardiomyocytes
      and collagen by the nonlinear optical microscopy techniques of multiphoton
      fluorescence/second harmonic generation showed a significant increase in collagen
      (> 10-fold) in chronically infected wild-type mice, whereas GPx1-/- mice
      exhibited a basal increase in collagen that did not change during the chronic
      phase. Chronically infected MnSODtg mice exhibited a marginal decline in
      mitochondrial DNA content and no changes in collagen signal in the myocardium.
      P47phox-/- mice lacking phagocyte-generated reactive oxygen species sustained a
      low level of myocardial oxidative stress and mitochondrial DNA damage in response
      to Trypanosoma cruzi infection. Yet chronically infected p47phox-/- mice
      exhibited increase in myocardial inflammatory and remodeling responses, similar
      to that noted in chronically infected wild-type mice. CONCLUSIONS: Inhibition of
      oxidative burst of phagocytes was not sufficient to prevent pathological cardiac
      remodeling in Chagas disease. Instead, enhancing the mitochondrial reactive
      oxygen species scavenging capacity was beneficial in controlling the inflammatory
      and oxidative pathology and the cardiac remodeling responses that are hallmarks
      of chronic Chagas disease.

PMID- 24136393
TI  - Anti-HBs seroconversion during treatment with entecavir in a patient with chronic
      hepatitis B virus infection on hemodialysis.
AB  - Hepatitis B (HBV) virus infection is one of the most important causes of liver
      disease in patients with end-stage renal failure on hemodialysis. The natural
      history of chronic HBV infection acquired in childhood starts with an immune
      tolerant phase, followed by an immune clearance phase that may lead to the
      inactive carrier state or the development of chronic liver disease. Information
      on antiviral therapy administered very early during the immune clearance phase
      are lacking and no data exist on the treatment of early immune activation in the
      hemodialysis setting. This report describes the case of a patient affected by end
      stage renal failure and HBeAg-positive chronic HBV virus infection treated very
      early during the immune clearance phase of HBV infection with an adjusted-dose of
      nucleoside analogue entecavir. The patient achieved a very rapid HBV-DNA
      undetectability, anti-HBe, and anti-HBs seroconversion. This is the first report
      of antiviral therapy with entecavir started during the immune reactive phase of
      HBV infection in a patient on hemodialysis and it suggests that antiviral
      treatment can enhance the effects of host immune activation resulting in
      biochemical, serological, and viral response, even in end-stage renal failure
      patients with partial immunodeficiency. Antiviral therapy with entecavir in the
      setting of hemodialysis was safe and well tolerated.

PMID- 24136394
TI  - Metabolic disorders: FGF21 analogue shows promise in the clinic.

PMID- 24136395
TI  - Lysosomal storage diseases: Thioesterase mimetic reduces toxicity.

PMID- 24136396
TI  - Does size matter in R&D productivity? If not, what does?

PMID- 24136397
TI  - Antibacterials: Resistance-guided discovery of new antibiotics.

PMID- 24136398
TI  - Treatment strategies for auricular avulsions: best practice.

PMID- 24136399
TI  - Association between lipid profile and depressive symptoms among Chinese older
      people: mediation by cardiovascular diseases?
AB  - BACKGROUND: The potential mediating effect of cardiovascular diseases (CVDs)
      (e.g., ischemic heart disease and stroke) on the association between abnormal
      serum lipids and late-life depressive symptoms has not been investigated.
      PURPOSE: We aimed to examine the associations between serum lipids and elevated
      depressive symptoms among older Chinese people and to determine the extent to
      which CVDs mediate their associations. METHOD: This cross-sectional study
      included 1,529 participants (age >=60 years, 59.2% women) in the Confucius
      Hometown Aging Project. In June 2010-July 2011, data were collected through an
      interview, clinical examinations, and laboratory tests. Abnormal serum lipids
      were defined according to international criteria and use of hypolipidemic drugs.
      Presence of elevated depressive symptoms was defined as the 15-item Geriatric
      Depression Scale score >=5. Data were analyzed with logistic and mediation models
      controlling for potential confounders. RESULTS: The prevalence of depressive
      symptoms was 20.3%. Depressive symptomatology was significantly associated with
      high total cholesterol, high triglycerides, low high-density lipoprotein
      cholesterol (HDL-C), high low-density lipoprotein cholesterol (LDL-C), and
      dyslipidemia (p < 0.05). The mediating effects on the associations of serum
      lipids with depressive symptoms were statistically significant for ischemic heart
      disease and stroke with the proportion of mediating effects over the total
      effects ranging 4.7-7.0% and 7.3-12.1%, respectively. CONCLUSION: Elevated
      depressive symptoms are associated with lipid profile characterized by high
      cholesterol, high triglycerides, low HDL-C, high LDL-C, and dyslipidemia; the
      associations are partially mediated by ischemic heart disease and stroke. These
      findings imply that unfavorable lipid profile may be involved in late-life
      depressive symptoms independent of atherosclerotic disorders.

PMID- 24136400
TI  - Somatic symptoms and holistic thinking as major dimensions behind modern health
      worries.
AB  - BACKGROUND: Modern health worries (MHWs) were related to somatic symptoms and to
      preference of holistic healing methods in previous studies. PURPOSE: The study
      aimed to investigate the contribution of symptom-related and holism-related
      factors to MHWs. METHODS: Participants (visitors of an Internet news portal; N =
      16152; 64.1 % males) completed a questionnaire assessing MHWs, somatosensory
      amplification, somatic symptoms, positive and negative affect, spirituality,
      holistic health beliefs, and various aspects of health care utilization (both
      conventional and alternative). RESULTS: Exploratory factor analysis with oblique
      rotation revealed two independent dimensions ("Somatic symptom distress" and
      "Holism") MHWs were involved with factor loadings of 0.294 and 0.417,
      respectively. The existence of two factors was supported by the results of
      confirmatory factor analysis. No practically significant interaction between the
      two factors was found in binary logistic regression analysis. Positive and
      negative affect, somatosensory amplification, spirituality, and holistic health
      beliefs were positively connected, while self-rated health status was negatively
      connected to MHWs even after controlling for socio-demographic and treatment
      related variables. CONCLUSIONS: Holistic thinking and symptom-related behavioral
      and psychological factors are independently associated with MHWs. Modern health
      worries can be conceptualized as symptom-related by-products of a holistic
      spiritual worldview.

PMID- 24136401
TI  - Insomnia symptoms, depressive symptoms, and suicide ideation in Japanese white
      collar employees.
AB  - BACKGROUND: Although poor sleep quality is the most common subjective complaint
      of workers and is a risk factor for depressive symptoms and suicide, researchers
      have not yet provided definitive links between insomnia symptoms, depressive
      symptoms, and suicide. PURPOSE: In our mediation model, we hypothesized
      relationships among insomnia symptoms, depressive symptoms, and suicide ideation.
      The purpose here was to use structural equation modeling (SEM) to test our
      mediation model. METHOD: Three hundred forty-three Japanese full-time white
      collar workers completed the measures to assess insomnia symptoms, depressive
      symptoms, and suicide ideation over an approximately 3-month period. RESULTS: A
      SEM analysis revealed that insomnia symptoms were positively and significantly
      associated with depressive symptoms, and depressive symptoms were positively and
      significantly associated with suicide ideation. Two tests showed a significant
      indirect effect of insomnia symptoms on suicide ideation through depressive
      symptoms. Thus, these results supported our mediation model. CONCLUSION: We
      conclude that insomnia symptoms were positively associated with suicidal
      ideation, though this relation was accounted for by depressive symptoms in
      Japanese white-collar workers.

PMID- 24136402
TI  - Alzheimer disease and amyotrophic lateral sclerosis: an etiopathogenic
      connection.
AB  - The etiopathogenesis of neither the sporadic form of Alzheimer disease (AD) nor
      of amyotrophic lateral sclerosis (ALS) is well understood. The activity of
      protein phosphatase-2A (PP2A), which regulates the phosphorylation of tau and
      neurofilaments, is negatively regulated by the myeloid leukemia-associated
      protein SET, also known as inhibitor-2 of PP2A, I2(PP2A). In AD brain, PP2A
      activity is compromised, probably because I2(PP2A) is overexpressed and is
      selectively cleaved at asparagine 175 into an N-terminal fragment, I2NTF, and a C
      terminal fragment, I2CTF, and both fragments inhibit PP2A. Here, we analyzed the
      spinal cords from ALS and control cases for I2(PP2A) cleavage and PP2A activity.
      As observed in AD brain, we found a selective increase in the cleavage of
      I2(PP2A) into I2NTF and I2CTF and inhibition of the activity and not the
      expression of PP2A in the spinal cords of ALS cases. To test the hypothesis that
      both AD and ALS could be triggered by I2CTF, a cleavage product of I2(PP2A), we
      transduced by intracerebroventricular injections newborn rats with adeno
      associated virus serotype 1 (AAV1) containing human I2CTF. AAV1-I2CTF produced
      reference memory impairment and tau pathology, and intraneuronal accumulation of
      Abeta by 5-8 months, and motor deficit and hyperphosphorylation and proliferation
      of neurofilaments, tau and TDP-43 pathologies, degeneration and loss of motor
      neurons and axons in the spinal cord by 10-14 months in rats. These findings
      suggest a previously undiscovered etiopathogenic relationship between sporadic
      forms of AD and ALS that is linked to I2(PP2A) and the potential of I2(PP2A)
      based therapeutics for these diseases.

PMID- 24136403
TI  - Speciation studies of vanadium in human liver (HepG2) cells after in vitro
      exposure to bis(maltolato)oxovanadium(IV) using HPLC online with elemental and
      molecular mass spectrometry.
AB  - A large number of studies has been published proposing a range of vanadium
      containing compounds as potential new anti-diabetic drugs due to the observed
      insulin mimetic function of V(IV) complexes. Vanadium uptake and distribution
      within the body have been investigated in animal models by determination of total
      vanadium concentrations. Phase I and phase IIa human clinical trials have been
      completed with the ethyl analogue of bis(maltolato)oxovanadium(IV) (BMOV). Mass
      spectrometry studies have focused on the characterisation of vanadium transferrin
      in body fluids after incubation with BMOV. However, the application of hyphenated
      mass spectrometric techniques for the identification of low molecular mass
      mediating vanadium metabolites in human body fluids or tissues after exposure to
      BMOV or in more simplified and cheaper models such as in vitro diabetes models
      has not been reported yet. This paper describes for the first time methodology
      for the characterisation of the predominant anionic vanadium metabolite in a
      liver cell model after exposure to BMOV. Total vanadium determination in cell
      lysates indicated significant uptake of vanadium. Size exclusion chromatography
      was applied with combined elemental and molecular mass spectrometric detection
      for vanadium speciation analysis in the cell lysates. The effect of cell medium
      and lysis conditions on the observed vanadium metabolites was studied. For the
      first time stable isotope labelling was applied to BMOV in order to achieve
      unambiguous correlation between elemental and molecular mass spectrometric
      results. Candidate elemental formulae for the unknown metabolite were derived
      based on accurate mass measurements. The most likely candidate formula combined
      with MS/MS fragmentation data is consistent with the presence of a divanadate
      phosphate derivate.

PMID- 24136405
TI  - DNA-bearing membrane vesicles produced by Ahrensia kielensis and
      Pseudoalteromonas marina.
AB  - Outer membrane vesicles (OMVs) derived from the alphaproteobacterium Ahrensia
      kielensis and from Pseudoalteromonas marina, a gammaproteobacterium, were sampled
      from liquid cultures in order to extract the MV-associated DNA, establish a
      shotgun library, and sequence randomly chosen clones to determine the origins of
      their DNA. We show that OMVs from A. kielensis and from P. marina both harbour
      DNA larger than 20 or 30 kbp. Transmission electron microscopical inspection of
      OMVs of A. kielensis and P. marina showed two types of vesicles: bilayered OMVs
      with a diameter between 30 and 250 nm and double bilayered OMVs ranging between
      80 and 200 nm. Bilayered OMVs are either characterized by the presence of a large
      electron-dense substance or are elctron translucent. Double bilayered OMVs
      contained an electron dense substance in the core region surrounded by the second
      bilayer. 30,094 bp of the genome from OMV of A. kielensis and 45,981 bp of that
      from P. marina were sequenced. The results indicated that all sequences were
      single copy and that all sequences, with one exception, were similar to
      prokaryotic sequences, inserted viral sequences were not detected.

PMID- 24136404
TI  - Gene signatures related to B-cell proliferation predict influenza vaccine-induced
      antibody response.
AB  - Vaccines are very effective at preventing infectious disease but not all
      recipients mount a protective immune response to vaccination. Recently, gene
      expression profiles of PBMC samples in vaccinated individuals have been used to
      predict the development of protective immunity. However, the magnitude of change
      in gene expression that separates vaccine responders and nonresponders is likely
      to be small and distributed across networks of genes, making the selection of
      predictive and biologically relevant genes difficult. Here we apply a new
      approach to predicting vaccine response based on coordinated upregulation of sets
      of biologically informative genes in postvaccination gene expression profiles. We
      found that enrichment of gene sets related to proliferation and immunoglobulin
      genes accurately segregated high responders to influenza vaccination from low
      responders and achieved a prediction accuracy of 88% in an independent clinical
      trial. Many of the genes in these gene sets would not have been identified using
      conventional, single-gene level approaches because of their subtle upregulation
      in vaccine responders. Our results demonstrate that gene set enrichment method
      can capture subtle transcriptional changes and may be a generally useful approach
      for developing and interpreting predictive models of the human immune response. 

PMID- 24136406
TI  - Factor IX-Padua enhances the fibrinolytic resistance of plasma clots.
AB  - Hypercoagulable conditions may determine a hypofibrinolytic state by increasing
      the activation of thrombin-activatable fibrinolysis inhibitor (TAFI). Factor
      (F)IX-Padua is a mutated FIX with an eight-fold increased clotting activity and
      associates with a higher venous thrombotic risk. We evaluated the influence of
      FIX-Padua on TAFI-mediated regulation of fibrinolysis. A subject hemizygous for
      FIX-Padua, two family members (heterozygous and normal) and six healthy controls
      were studied. Clot lysis, TAFI activation and thrombin generation were evaluated
      in contact-inhibited plasma challenged with low concentrations of tissue factor.
      Fibrinolysis times were significantly longer in FIX-Padua carriers than controls.
      The difference disappeared when activated TAFI (TAFIa) was inhibited, when TAFI
      activation was avoided or when clotting was made independent of FIX. TAFIa
      generation was markedly enhanced in FIX-Padua carriers as compared to controls,
      and this could be explained by a greater thrombin generation in the former.
      Hyperactive FIX, but not wild-type FIX, enhanced fibrinolytic resistance also
      when the FXI-dependent positive feedback was blocked by a neutralising anti-FXI
      antibody. This thrombin-mediated, TAFI-dependent down-regulation of fibrinolysis
      provides new clues for explaining the heightened thrombotic risk in subjects
      carrying the FIX-Padua mutation.

PMID- 24136407
TI  - Suitability and repeatability of a photostress recovery test device, the macular
      degeneration detector (MDD-2), for diabetes and diabetic retinopathy assessment.
AB  - BACKGROUND: Diabetic retinopathy can result in impaired photostress recovery time
      despite normal visual acuity and fundoscopic appearance. The Macular Degeneration
      Detector (MDD-2) is a novel flash photostress recovery time device. In this
      study, we examine the repeatability of the MDD-2 in normal and diabetic subjects.
      METHODS: One hundred and ninety one (90 women, 101 men) subjects were recruited
      and divided into 1 of the 3 study groups (normal controls, n = 40; diabetes no
      retinopathy, n = 98; nonproliferative diabetic retinopathy, n = 53). Photostress
      recovery time was measured three times in the study eye using the MDD-2, each
      measurement separated by a 5-minute interval. RESULTS: Repeated measures analysis
      of variance revealed no statistically significant learning or fatigue effects on
      intrameasurement repeatability for any group. Photostress recovery time measures
      were broadly similar and typically not statistically significantly different
      between study groups. The coefficient of repeatability reached clinically
      acceptable levels once the initial photostress recovery time measure, which
      demonstrated increased variability and latency compared with all subsequent
      measures, was excluded. CONCLUSION: The MDD-2 seems to provide repeatable
      photostress recovery time measurements among naive diabetic subjects. The device
      does not, however, seem capable of differentiating normal and nonproliferative
      diabetic eyes, and would not be suitable for inclusion in diabetic retinopathy
      screening protocol.

PMID- 24136408
TI  - Endophthalmitis after intravitreal injection: decreasing incidence and clinical
      outcome-8-year results from a tertiary ophthalmic referral center.
AB  - PURPOSE: To report the incidence, clinical features, microbiologic culture
      results, management and visual outcome of patients with endophthalmitis after
      intravitreal injections (IVTs). METHODS: This retrospective chart review included
      all patients receiving IVTs between January 2005 and July 2012. Cases of
      suspected and confirmed endophthalmitis after IVT were identified and reviewed.
      RESULTS: A total of 20,179 IVTs were perfomed during the study period. Six cases
      of supected endophthalmitis were identified clinically (0.03%), of which 3 were
      culture positive (0.015%). The risk of culture-positive post-IVT endophthalmitis
      was 2/8,882 (0.023%) in the 2005 to 2008 period and 1/11,297 (0.009%) in the
      period 2009 to 2012. Symptoms developed within the first 3 days after IVT in 4 of
      the 6 patients and visual acuity was reduced to hand motion in 4 of the 6
      patients. Microbiologic specimens were positive on 3 of the 6 cases (coagulase
      negative Staphylococcus, n = 2; Staphylococcus aureus, n = 1). Mean visual acuity
      before patients with endophthalmitis was 20/100, whereas mean final visual acuity
      at last follow-up was 20/200. CONCLUSION: The incidence of endophthalmitis after
      IVT was low with no cases because of Streptococcus species in the present setting
      using povidone-iodine in the preoperative disinfection of the conjunctival sac.
      Therefore, adherence to standardized protocols including the use of povidone
      iodine when performing IVTs is recommended.

PMID- 24136409
TI  - Optical coherence tomography findings of the vitreoretinal interface in
      asymptomatic fellow eyes of patients with acute posterior vitreous detachment.
AB  - PURPOSE: To describe the vitreoretinal interface of the asymptomatic fellow eyes
      of patients with acute unilateral posterior vitreous detachment (PVD) based on
      biomicroscopic examination and spectral domain optical coherence tomography.
      METHODS: Sixty-five eyes of 65 consecutive patients with acute unilateral PVD
      were examined by slit-lamp, indirect ophthalmoscopy, and spectral domain optical
      coherence tomography. The state of PVD in different retinal locations and
      premacular pocket were assessed and graded using spectral domain optical
      coherence tomography. RESULTS: Nine eyes (13.85%) had no PVD, 15 (23.08%) had
      extrafoveal vitreous separation (Stage 1), 18 (27.69%) had partial foveal
      vitreous separation (Stage 2), 12 (18.46%) had complete foveal vitreous
      separation (Stage 3), and 11 (16.92%) had a complete PVD (Stage 4). The presence
      of a premacular pocket showed equal distribution in Stages 0, 1, and 2 (66.67,
      80.00, and 77.78%, respectively) but was significantly less common in Stages 3 (P
      = 0.016) and 4 (P < 0.0001). Only certain posterior vitreous configurations were
      identified (P < 0.0001), suggesting an orderly progression of PVD evolution.
      CONCLUSION: Our spectral domain optical coherence tomography-based PVD staging
      system describes the evolution of PVDs. This can be used as a guide in predicting
      the occurrence and evolution of PVD in this population.

PMID- 24136410
TI  - Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue
      factor tTF-NGR using multi-modal imaging.
AB  - The fusion protein tTF-NGR consists of the extracellular domain of the
      thrombogenic human tissue factor (truncated tissue factor, tTF) and the peptide
      GNGRAHA (NGR), a ligand of the surface protein CD13 (aminopeptidase N),
      upregulated on endothelial cells of tumor vessels. tTF-NGR preferentially
      activates blood coagulation within tumor vasculature, resulting in tumor vessel
      infarction and subsequent tumor growth retardation/regression. The anti-vascular
      mechanism of the tTF-NGR therapy approach was verified by quantifying the reduced
      tumor blood-perfusion with contrast-enhanced ultrasound, the reduced relative
      tumor blood volume by ultrasmall superparamagnetic iron oxide-enhanced magnetic
      resonance imaging, and by in vivo-evaluation of hemorrhagic bleeding with
      fluorescent biomarkers (AngioSense(680)) in fluorescence reflectance imaging. The
      accumulation of tTF-NGR within the tumor was proven by visualizing the
      distribution of the iodine-123-labelled protein by single-photon emission
      computed tomography. Use of these multi-modal vascular and molecular imaging
      tools helped to assess the therapeutic effect even at real time and to detect non
      responding tumors directly after the first tTF-NGR treatment. This emphasizes the
      importance of imaging within clinical studies with tTF-NGR. The imaging
      techniques as used here have applicability within a wider scope of therapeutic
      regimes interfering with tumor vasculature. Some even are useful to obtain
      predictive biosignals in personalized cancer treatment. 

PMID- 24136411
TI  - Anatomy, function, and evolution of jaw and hyobranchial muscles in
      cryptobranchoid salamander larvae.
AB  - Larval salamanders (Lissamphibia: Caudata) are known to be effective suction
      feeders in their aquatic environments, although they will eventually transform
      into terrestrial tongue feeding adults during metamorphosis. Early tetrapods may
      have had a similar biphasic life cycle and this makes larval salamanders a
      particularly interesting model to study the anatomy, function, development, and
      evolution of the feeding apparatus in terrestrial vertebrates. Here, we provide a
      description of the muscles that are involved in the feeding strike in salamander
      larvae of the Hynobiidae and compare them to larvae of the paedomorphic
      Cryptobranchidae. We provide a functional and evolutionary interpretation for the
      observed muscle characters. The cranial muscles in larvae from species of the
      Hynobiidae and Cryptobranchidae are generally very similar. Most notable are the
      differences in the presence of the m. hyomandibularis, a muscle that connects the
      hyobranchial apparatus with the lower jaw. We found this muscle only in
      Onychodactylus japonicus (Hynobiidae) but not in other hynobiid or cryptobranchid
      salamanders. Interestingly, the m. hyomandibularis in O. japonicus originates
      from the ceratobranchial I and not the ceratohyal, and thus exhibits what was
      previously assumed to be the derived condition. Finally, we applied a
      biomechanical model to simulate suction feeding in larval salamanders. We provide
      evidence that a flattened shape of the hyobranchial apparatus in its resting
      position is beneficial for a fast and successful suction feeding strike.

PMID- 24136412
TI  - Emerging infections of the central nervous system.
AB  - Emerging infections affecting the central nervous system often present as
      encephalitis and can cause substantial morbidity and mortality. Diagnosis
      requires not only careful history taking, but also the application of newly
      developed diagnostic tests. These diseases frequently occur in outbreaks stemming
      from viruses that have mutated from an animal host and gained the ability to
      infect humans. With globalization, this can translate to the rapid emergence of
      infectious clusters or the establishment of endemicity in previously naive
      locations. Since these infections are often vector borne and effective treatments
      are almost uniformly lacking, prevention is at least as important as prompt
      diagnosis and institution of supportive care. In this review, we focus on some of
      the recent literature addressing emerging and resurging viral encephalitides in
      the United States and around the world-specifically, West Nile virus, dengue,
      polio, and cycloviruses. We also discuss new, or "emerging," techniques for the
      precise and rapid diagnosis of encephalitides. 

PMID- 24136414
TI  - Paving a regulatory pathway for phage therapy. Europe should muster the resources
      to financially, technically and legally support the introduction of phage
      therapy.

PMID- 24136413
TI  - Tpo1-mediated spermine and spermidine export controls cell cycle delay and times
      antioxidant protein expression during the oxidative stress response.
AB  - Cells counteract oxidative stress by altering metabolism, cell cycle and gene
      expression. However, the mechanisms that coordinate these adaptations are only
      marginally understood. Here we provide evidence that timing of these responses in
      yeast requires export of the polyamines spermidine and spermine. We show that
      during hydrogen peroxide (H2O2) exposure, the polyamine transporter Tpo1 controls
      spermidine and spermine concentrations and mediates induction of antioxidant
      proteins, including Hsp70, Hsp90, Hsp104 and Sod1. Moreover, Tpo1 determines a
      cell cycle delay during adaptation to increased oxidant levels, and affects H2O2
      tolerance. Thus, central components of the stress response are timed through Tpo1
      controlled polyamine export. 

PMID- 24136415
TI  - Animals in research: a stony road. The implementation of the European Union
      directive on the use of animals in research into national laws is struggling.

PMID- 24136416
TI  - Reciprocal changes in cervical spine alignment after corrective thoracolumbar
      deformity surgery.
AB  - PURPOSE: To identify changes in cervical alignment parameters following surgical
      correction of thoracolumbar deformity and then assess the preoperative parameters
      which induce changes in cervical alignment following corrective thoracolumbar
      deformity surgery. METHODS: A retrospective study of 49 patients treated for
      thoracolumbar deformity with preoperative planning of an acceptably aligned
      coronal and sagittal plane in each case. We compared cervical spine parameters in
      two distinct low [preoperative C7 sagittal vertical axis (SVA) <= 6 cm] and high
      (preoperative C7 SVA >= 9 cm) C7 SVA groups. Multilinear regression analysis was
      performed and revealed the relationship between postoperative cervical lordosis
      and preoperative spinopelvic parameters and surgical plans. RESULTS: In the lower
      C7 SVA group, cervical lordosis was significantly increased after thoracic/lumbar
      deformity correction (p < 0.01). In contrast, the high C7 SVA group showed
      decreased cervical lordosis postoperatively (p < 0.01). Multilinear regression
      analysis demonstrated the preoperative parameters (preoperative C2-7 angle, T1
      slope, surgical plan for PT and C7 SVA), which determine the postoperative
      cervical lordosis. CONCLUSION: In spinal deformity procedures, preoperative
      spinal alignment parameters, and surgical plans could affect postoperative
      cervical spine alignment.

PMID- 24136418
TI  - Selective estrogen receptor modulation prevents scoliotic curve progression:
      radiologic and histomorphometric study on a bipedal C57Bl6 mice model.
AB  - PURPOSE: Previous work has suggested that progression of experimental scoliotic
      curves in pinealectomized chicken and bipedal C57BL6 mice models may be prevented
      and reversed with Tamoxifen treatment. Raloxifene is another Selective Estrogen
      Receptor Modulator (SERM) with estrogen agonist effects on bone and increases
      bone density but with fewer side effects on humans. To investigate whether
      scoliosis progression in bipedal C57Bl6 mice model could be prevented with SERM
      treatment and the mechanisms associated with this effect. METHODS: Eighty C57BL6
      mice were rendered bipedal and divided into Tamoxifen (TMX), Raloxifene (RLX) and
      control groups. TMX and RLX groups received orally administered TMX and RLX for
      40 weeks. Anteroposterior X-ray imaging and histomorphometric analysis (at 20th
      and 40th weeks) were performed. RESULTS: At 20th week, TMX and RLX groups
      displayed higher rates (p = 0.033, p = 0.029) and larger curve magnitudes (p =
      0.018). At 40th week, curve rates were similar between the groups but the curve
      magnitudes in TMX and RLX groups were smaller (p = 0.001). Histomorphometry
      revealed that treated animals had higher trabecular density (p = 0.04), lower
      total intervertebral disc (p = 0.038) and growth plate volumes (p = 0.005) and
      smaller vertebral bodies (p = 0.016). CONCLUSIONS: Treatment with TMX or RLX did
      not reduce the incidence of scoliosis but decreased the curve magnitudes at 40
      weeks. The underlying mechanism associated with the decrease in curve magnitudes
      may be the early maturation of growth plates, thereby possible deceleration of
      the growth rate of the vertebral column and increase in bone density. RLX is as
      effective as TMX in preventing the progression of scoliotic curves in melatonin
      deficient bipedal mice.

PMID- 24136419
TI  - Inhaled formaldehyde induces DNA-protein crosslinks and oxidative stress in bone
      marrow and other distant organs of exposed mice.
AB  - Formaldehyde (FA), a major industrial chemical and ubiquitous environmental
      pollutant, has been classified as a leukemogen. The causal relationship remains
      unclear, however, due to limited evidence that FA induces toxicity in bone
      marrow, the site of leukemia induction, and in other distal organs. Although
      induction of DNA-protein crosslinks (DPC), a hallmark of FA toxicity, was not
      previously detected in the bone marrow of FA-exposed rats and monkeys in studies
      published in the 1980s, our recent studies showed increased DPC in the bone
      marrow, liver, kidney, and testes of exposed Kunming mice. To confirm these
      preliminary results, in the current study we exposed BALB/c mice to 0, 0.5, 1.0,
      and 3.0 mg m(-3) FA (8 hr per day, for 7 consecutive days) by nose-only
      inhalation and measured DPC levels in bone marrow and other organs of exposed
      mice. As oxidative stress is a potential mechanism of FA toxicity, we also
      measured glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde
      (MDA), in the bone marrow, peripheral blood mononuclear cells, lung, liver,
      spleen, and testes of exposed mice. Significant dose-dependent increases in DPC,
      decreases in GSH, and increases in ROS and MDA were observed in all organs
      examined (except for DPC in lung). Bone marrow was among the organs with the
      strongest effects for DPC, GSH, and ROS. In conclusion, exposure of mice to FA by
      inhalation induced genotoxicity and oxidative stress in bone marrow and other
      organs. These findings strengthen the biological plausibility of FA-induced
      leukemogenesis and systemic toxicity.

PMID- 24136421
TI  - Atrial tachycardia after cryoballoon ablation of paroxysmal atrial fibrillation.

PMID- 24136422
TI  - Atrial fibrillation ablation in a patient with absent right superior and
      persistent left superior vena cava.

PMID- 24136420
TI  - The juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical
      for ROP-induced growth in pollen tubes.
AB  - Polarized growth of pollen tubes is a critical step for successful reproduction
      in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP
      (Rho GTPases of plants) necessitates a complex and sophisticated regulatory
      system, in which guanine nucleotide exchange factors (RopGEFs) are key
      components. It was previously shown that a leucine-rich repeat receptor-like
      kinase, Arabidopsis pollen receptor kinase 2 (AtPRK2), interacted with RopGEF12
      for its membrane recruitment. However, the mechanisms underlying AtPRK2-mediated
      ROP activation in vivo are yet to be defined. It is reported here that over
      expression of AtPRK2 induced tube bulging that was accompanied by the ectopic
      localization of ROP-GTP and the ectopic distribution of actin microfilaments.
      Tube depolarization was also induced by a potentially kinase-dead mutant,
      AtPRK2K366R, suggesting that the over-expression effect of AtPRK2 did not require
      its kinase activity. By contrast, deletions of non-catalytic domains in AtPRK2,
      i.e. the juxtamembrane (JM) and carboxy-terminal (CT) domains, abolished its
      ability to affect tube polarization. Notably, AtPRK2K366R retained the ability to
      interact with RopGEF12, whereas AtPRK2 truncations of these non-catalytic domains
      did not. Lastly, it has been shown that the JM and CT domains of AtPRK2 were not
      only critical for its interaction with RopGEF12 but also critical for its
      distribution at the plasma membrane. These results thus provide further insight
      into pollen receptor kinase-mediated ROP activation during pollen tube growth. 

PMID- 24136423
TI  - Percutaneous nephrolithotomy for the treatment of radiolucent renal stones in
      children: is it different opaque stone treatment?
AB  - We aimed to evaluate the effectiveness of percutaneous nephrolithotomy (PNL),
      stone-free rates, and related complications in children with radiolucent renal
      stones. A total of 56 patients aged <16 years from four institutions were
      enrolled in our study. Asymptomatic, clinically insignificant residual fragments
      measuring <4 mm or a complete stone-free status was accepted as the criterion for
      clinical success. Complications were evaluated according to the modified Clavien
      classification. The mean age of the patients was 7.8 +/- 4.5 years. The mean
      stone size was calculated as 24.07 +/- 10.4 mm. The median operative and
      fluoroscopy times were 53.2 min (15-170 min) and 172.4 s (5-520 s), respectively.
      The success rate after PNL monotherapy was 87.4%; the total success rate with
      shock wave lithotripsy used as an auxillary treatment method was detected as
      94.6%. The total complication rate was 19.6% (11 patients). No adjacent organ
      injury was observed. All of the complications that occurred were minor according
      to the Clavien classification (Clavien Grades I-II). PNL can be applied to
      radiolucent pediatric renal stones in children with similar success, and
      complication rates as noted for radiopaque stones.

PMID- 24136424
TI  - Efficient human pose estimation from single depth images.
AB  - We describe two new approaches to human pose estimation. Both can quickly and
      accurately predict the 3D positions of body joints from a single depth image
      without using any temporal information. The key to both approaches is the use of
      a large, realistic, and highly varied synthetic set of training images. This
      allows us to learn models that are largely invariant to factors such as pose,
      body shape, field-of-view cropping, and clothing. Our first approach employs an
      intermediate body parts representation, designed so that an accurate per-pixel
      classification of the parts will localize the joints of the body. The second
      approach instead directly regresses the positions of body joints. By using simple
      depth pixel comparison features and parallelizable decision forests, both
      approaches can run super-real time on consumer hardware. Our evaluation
      investigates many aspects of our methods, and compares the approaches to each
      other and to the state of the art. Results on silhouettes suggest broader
      applicability to other imaging modalities. 

PMID- 24136425
TI  - SfM with MRFs: discrete-continuous optimization for large-scale structure from
      motion.
AB  - Recent work in structure from motion (SfM) has built 3D models from large
      collections of images downloaded from the Internet. Many approaches to this
      problem use incremental algorithms that solve progressively larger bundle
      adjustment problems. These incremental techniques scale poorly as the image
      collection grows, and can suffer from drift or local minima. We present an
      alternative framework for SfM based on finding a coarse initial solution using
      hybrid discrete-continuous optimization and then improving that solution using
      bundle adjustment. The initial optimization step uses a discrete Markov random
      field (MRF) formulation, coupled with a continuous Levenberg-Marquardt
      refinement. The formulation naturally incorporates various sources of information
      about both the cameras and points, including noisy geotags and vanishing point
      (VP) estimates. We test our method on several large-scale photo collections,
      including one with measured camera positions, and show that it produces models
      that are similar to or better than those produced by incremental bundle
      adjustment, but more robustly and in a fraction of the time. 

PMID- 24136426
TI  - Phrasal recognition.
AB  - In this paper, we introduce visual phrases, complex visual composites like "a
      person riding a horse." Visual phrases often display significantly reduced visual
      complexity compared to their component objects because the appearance of those
      objects can change profoundly when they participate in relations. We introduce a
      dataset suitable for phrasal recognition that uses familiar PASCAL object
      categories, and demonstrate significant experimental gains resulting from
      exploiting visual phrases. We show that a visual phrase detector significantly
      outperforms a baseline which detects component objects and reasons about
      relations, even though visual phrase training sets tend to be smaller than those
      for objects. We argue that any multiclass detection system must decode detector
      outputs to produce final results; this is usually done with nonmaximum
      suppression. We describe a novel decoding procedure that can account accurately
      for local context without solving difficult inference problems. We show this
      decoding procedure outperforms the state of the art. Finally, we show that
      decoding a combination of phrasal and object detectors produces real improvements
      in detector results. 

PMID- 24136427
TI  - Image-based separation of reflective and fluorescent components using
      illumination variant and invariant color.
AB  - Traditionally, researchers tend to exclude fluorescence from color appearance
      algorithms in computer vision and image processing because of its complexity. In
      reality, fluorescence is a very common phenomenon observed in many objects, from
      gems and corals, to different kinds of writing paper, and to our clothes. In this
      paper, we provide detailed theories of fluorescence phenomenon. In particular, we
      show that the color appearance of fluorescence is unaffected by illumination in
      which it differs from ordinary reflectance. Moreover, we show that the color
      appearance of objects with reflective and fluorescent components can be
      represented as a linear combination of the two components. A linear model allows
      us to separate the two components using images taken under unknown illuminants
      using independent component analysis (ICA). The effectiveness of the proposed
      method is demonstrated using digital images of various fluorescent objects. 

PMID- 24136428
TI  - Articulated human detection with flexible mixtures of parts.
AB  - We describe a method for articulated human detection and human pose estimation in
      static images based on a new representation of deformable part models. Rather
      than modeling articulation using a family of warped (rotated and foreshortened)
      templates, we use a mixture of small, nonoriented parts. We describe a general,
      flexible mixture model that jointly captures spatial relations between part
      locations and co-occurrence relations between part mixtures, augmenting standard
      pictorial structure models that encode just spatial relations. Our models have
      several notable properties: 1) They efficiently model articulation by sharing
      computation across similar warps, 2) they efficiently model an exponentially
      large set of global mixtures through composition of local mixtures, and 3) they
      capture the dependency of global geometry on local appearance (parts look
      different at different locations). When relations are tree structured, our models
      can be efficiently optimized with dynamic programming. We learn all parameters,
      including local appearances, spatial relations, and co-occurrence relations
      (which encode local rigidity) with a structured SVM solver. Because our model is
      efficient enough to be used as a detector that searches over scales and image
      locations, we introduce novel criteria for evaluating pose estimation and human
      detection, both separately and jointly. We show that currently used evaluation
      criteria may conflate these two issues. Most previous approaches model limbs with
      rigid and articulated templates that are trained independently of each other,
      while we present an extensive diagnostic evaluation that suggests that flexible
      structure and joint training are crucial for strong performance. We present
      experimental results on standard benchmarks that suggest our approach is the
      state-of-the-art system for pose estimation, improving past work on the
      challenging Parse and Buffy datasets while being orders of magnitude faster. 

PMID- 24136429
TI  - Intrinsic image decomposition using a sparse representation of reflectance.
AB  - Intrinsic image decomposition is an important problem that targets the recovery
      of shading and reflectance components from a single image. While this is an ill
      posed problem on its own, we propose a novel approach for intrinsic image
      decomposition using reflectance sparsity priors that we have developed. Our
      sparse representation of reflectance is based on a simple observation:
      Neighboring pixels with similar chromaticities usually have the same reflectance.
      We formalize and apply this sparsity constraint on local reflectance to construct
      a data-driven second-generation wavelet representation. We show that the
      reflectance component of natural images is sparse in this representation. We
      further propose and formulate a global sparse constraint on reflectance colors
      using the assumption that each natural image uses a small set of material colors.
      Using this sparse reflectance representation and the global constraint on a
      sparse set of reflectance colors, we formulate a constrained l1-norm minimization
      problem for intrinsic image decomposition that can be solved efficiently. Our
      algorithm can successfully extract intrinsic images from a single image without
      using color models or any user interaction. Experimental results on a variety of
      images demonstrate the effectiveness of the proposed technique.

PMID- 24136430
TI  - Iterative quantization: a Procrustean approach to learning binary codes for large
      scale image retrieval.
AB  - This paper addresses the problem of learning similarity-preserving binary codes
      for efficient similarity search in large-scale image collections. We formulate
      this problem in terms of finding a rotation of zero-centered data so as to
      minimize the quantization error of mapping this data to the vertices of a zero
      centered binary hypercube, and propose a simple and efficient alternating
      minimization algorithm to accomplish this task. This algorithm, dubbed iterative
      quantization (ITQ), has connections to multiclass spectral clustering and to the
      orthogonal Procrustes problem, and it can be used both with unsupervised data
      embeddings such as PCA and supervised embeddings such as canonical correlation
      analysis (CCA). The resulting binary codes significantly outperform several other
      state-of-the-art methods. We also show that further performance improvements can
      result from transforming the data with a nonlinear kernel mapping prior to PCA or
      CCA. Finally, we demonstrate an application of ITQ to learning binary attributes
      or "classemes" on the ImageNet data set.

PMID- 24136431
TI  - Localizing parts of faces using a consensus of exemplars.
AB  - We present a novel approach to localizing parts in images of human faces. The
      approach combines the output of local detectors with a nonparametric set of
      global models for the part locations based on over 1,000 hand-labeled exemplar
      images. By assuming that the global models generate the part locations as hidden
      variables, we derive a Bayesian objective function. This function is optimized
      using a consensus of models for these hidden variables. The resulting localizer
      handles a much wider range of expression, pose, lighting, and occlusion than
      prior ones. We show excellent performance on real-world face datasets such as
      Labeled Faces in the Wild (LFW) and a new Labeled Face Parts in the Wild (LFPW)
      and show that our localizer achieves state-of-the-art performance on the less
      challenging BioID dataset. 

PMID- 24136432
TI  - On differential photometric reconstruction for unknown, isotropic BRDFs.
AB  - This paper presents a comprehensive theory of photometric surface reconstruction
      from image derivatives in the presence of a general, unknown isotropic BRDF. We
      derive precise topological classes up to which the surface may be determined and
      specify exact priors for a full geometric reconstruction. These results are the
      culmination of a series of fundamental observations. First, we exploit the
      linearity of chain rule differentiation to discover photometric invariants that
      relate image derivatives to the surface geometry, regardless of the form of
      isotropic BRDF. For the problem of shape-from-shading, we show that a
      reconstruction may be performed up to isocontours of constant magnitude of the
      gradient. For the problem of photometric stereo, we show that just two
      measurements of spatial and temporal image derivatives, from unknown light
      directions on a circle, suffice to recover surface information from the
      photometric invariant. Surprisingly, the form of the invariant bears a striking
      resemblance to optical flow; however, it does not suffer from the aperture
      problem. This photometric flow is shown to determine the surface up to
      isocontours of constant magnitude of the surface gradient, as well as isocontours
      of constant depth. Further, we prove that specification of the surface normal at
      a single point completely determines the surface depth from these isocontours. In
      addition, we propose practical algorithms that require additional initial or
      boundary information, but recover depth from lower order derivatives. Our
      theoretical results are illustrated with several examples on synthetic and real
      data. 

PMID- 24136433
TI  - Paired regions for shadow detection and removal.
AB  - In this paper, we address the problem of shadow detection and removal from single
      images of natural scenes. Differently from traditional methods that explore pixel
      or edge information, we employ a region-based approach. In addition to
      considering individual regions separately, we predict relative illumination
      conditions between segmented regions from their appearances and perform pairwise
      classification based on such information. Classification results are used to
      build a graph of segments, and graph-cut is used to solve the labeling of shadow
      and nonshadow regions. Detection results are later refined by image matting, and
      the shadow-free image is recovered by relighting each pixel based on our lighting
      model. We evaluate our method on the shadow detection dataset in Zhu et al. In
      addition, we created a new dataset with shadow-free ground truth images, which
      provides a quantitative basis for evaluating shadow removal. We study the
      effectiveness of features for both unary and pairwise classification.

PMID- 24136434
TI  - Robust visual tracking using local sparse appearance model and K-selection.
AB  - Online learned tracking is widely used for its adaptive ability to handle
      appearance changes. However, it introduces potential drifting problems due to the
      accumulation of errors during the self-updating, especially for occluded
      scenarios. The recent literature demonstrates that appropriate combinations of
      trackers can help balance the stability and flexibility requirements. We have
      developed a robust tracking algorithm using a local sparse appearance model (SPT)
      and K-Selection. A static sparse dictionary and a dynamically updated online
      dictionary basis distribution are used to model the target appearance. A novel
      sparse representation-based voting map and a sparse constraint regularized mean
      shift are proposed to track the object robustly. Besides these contributions, we
      also introduce a new selection-based dictionary learning algorithm with a locally
      constrained sparse representation, called K-Selection. Based on a set of
      comprehensive experiments, our algorithm has demonstrated better performance than
      alternatives reported in the recent literature. 

PMID- 24136435
TI  - Toward wide-angle microvision sensors.
AB  - Achieving computer vision on microscale devices is a challenge. On these
      platforms, the power and mass constraints are severe enough for even the most
      common computations (matrix manipulations, convolution, etc.) to be difficult.
      This paper proposes and analyzes a class of miniature vision sensors that can
      help overcome these constraints. These sensors reduce power requirements through
      template-based optical convolution, and they enable a wide field-of-view within a
      small form through a refractive optical design. We describe the tradeoffs between
      the field-of-view, volume, and mass of these sensors and we provide analytic
      tools to navigate the design space. We demonstrate milliscale prototypes for
      computer vision tasks such as locating edges, tracking targets, and detecting
      faces. Finally, we utilize photolithographic fabrication tools to further
      miniaturize the optical designs and demonstrate fiducial detection onboard a
      small autonomous air vehicle. 

PMID- 24136436
TI  - A minimum volume covering approach with a set of ellipsoids.
AB  - A technique for adjusting a minimum volume set of covering ellipsoids technique
      is elaborated. Solutions to this problem have potential application in one-class
      classification and clustering problems. Its main original features are: 1) It
      avoids the direct evaluation of determinants by using diagonalization properties
      of the involved matrices, 2) it identifies and removes outliers from the
      estimation process, 3) it avoids binary variables resulting from the
      combinatorial character of the assignment problem that are replaced by continuous
      variables in the range [0,1], 4) the problem can be solved by a bilevel algorithm
      that in its first level determines the ellipsoids and in its second level
      reassigns the data points to ellipsoids and identifies outliers based on an
      algorithm that forces the Karush-Kuhn-Tucker conditions to be satisfied. Two
      theorems provide rigorous bases for the proposed methods. Finally, a set of
      examples of application in different fields is given to illustrate the power of
      the method and its practical performance.

PMID- 24136437
TI  - Contextualized trajectory parsing with spatiotemporal graph.
AB  - This work investigates how to automatically parse object trajectories in
      surveillance videos, which aims at jointly solving three subproblems: 1) spatial
      segmentation, 2) temporal tracking, and 3) object categorization. We present a
      novel representation spatiotemporal graph (ST-Graph) in which: 1) Graph nodes
      express the motion primitives, each representing a short sequence of small-size
      patches over consecutive images, and 2) every two neighbor nodes are linked with
      either a positive edge or a negative edge to describe their collaborative or
      exclusive relationship of belonging to the same object trajectory. Phrasing the
      trajectory parsing as a graph multicoloring problem, we propose a unified
      probabilistic formulation to integrate various types of context knowledge as
      informative priors. An efficient composite cluster sampling algorithm is employed
      in search of the optimal solution by exploiting both the collaborative and the
      exclusive relationships between nodes. The proposed framework is evaluated over
      challenging videos from public datasets, and results show that it can achieve
      state-of-the-art tracking accuracy. 

PMID- 24136438
TI  - Forward basis selection for pursuing sparse representations over a dictionary.
AB  - The forward greedy selection algorithm of Frank and Wolfe has recently been
      applied with success to coordinate-wise sparse learning problems, characterized
      by a tradeoff between sparsity and accuracy. In this paper, we generalize this
      method to the setup of pursuing sparse representations over a prefixed
      dictionary. Our proposed algorithm iteratively selects an atom from the
      dictionary and minimizes the objective function over the linear combinations of
      all the selected atoms. The rate of convergence of this greedy selection
      procedure is analyzed. Furthermore, we extend the algorithm to the setup of
      learning nonnegative and convex sparse representation over a dictionary.
      Applications of the proposed algorithms to sparse precision matrix estimation and
      low-rank subspace segmentation are investigated with efficiency and effectiveness
      validated on benchmark datasets. 

PMID- 24136440
TI  - Sparse canonical correlation analysis: new formulation and algorithm.
AB  - In this paper, we study canonical correlation analysis (CCA), which is a powerful
      tool in multivariate data analysis for finding the correlation between two sets
      of multidimensional variables. The main contributions of the paper are: 1) to
      reveal the equivalent relationship between a recursive formula and a trace
      formula for the multiple CCA problem, 2) to obtain the explicit characterization
      for all solutions of the multiple CCA problem even when the corresponding
      covariance matrices are singular, 3) to develop a new sparse CCA algorithm, and
      4) to establish the equivalent relationship between the uncorrelated linear
      discriminant analysis and the CCA problem. We test several simulated and real
      world datasets in gene classification and cross-language document retrieval to
      demonstrate the effectiveness of the proposed algorithm. The performance of the
      proposed method is competitive with the state-of-the-art sparse CCA algorithms. 

PMID- 24136439
TI  - Pose-robust recognition of low-resolution face images.
AB  - Face images captured by surveillance cameras usually have poor resolution in
      addition to uncontrolled poses and illumination conditions, all of which
      adversely affect the performance of face matching algorithms. In this paper, we
      develop a completely automatic, novel approach for matching surveillance quality
      facial images to high-resolution images in frontal pose, which are often
      available during enrollment. The proposed approach uses multidimensional scaling
      to simultaneously transform the features from the poor quality probe images and
      the high-quality gallery images in such a manner that the distances between them
      approximate the distances had the probe images been captured in the same
      conditions as the gallery images. Tensor analysis is used for facial landmark
      localization in the low-resolution uncontrolled probe images for computing the
      features. Thorough evaluation on the Multi-PIE dataset and comparisons with state
      of-the-art super-resolution and classifier-based approaches are performed to
      illustrate the usefulness of the proposed approach. Experiments on surveillance
      imagery further signify the applicability of the framework. We also show the
      usefulness of the proposed approach for the application of tracking and
      recognition in surveillance videos. 

PMID- 24136441
TI  - A coprime blur scheme for data security in video surveillance.
AB  - This paper presents a novel coprime blurred pair (CBP) model to improve data
      security in camera surveillance. While most previous approaches have focused on
      completely encrypting the video stream, we introduce a spatial encryption scheme
      by strategically blurring the image/video contents. Specifically, we form a
      public stream and a private stream by blurring the original video data using two
      different kernels. Each blurred stream will provide the user who has lower
      clearance less access to personally identifiable details while still allowing
      behavior to be monitored. If the behavior is recognized as suspicious, a
      supervisor can use both streams to deblur the contents. Our approach is based on
      a new CBP theory where the two kernels are coprime when mapped to bivariate
      polynomials in the $(z)$ domain. We show that coprimality can be derived in terms
      of the rank of Bezout matrix formed by sampled polynomials, and we present an
      efficient algorithm to factor the Bezout matrix for recovering the latent image.
      To make our solution practical, we implement our decryption scheme on a graphics
      processing unit (GPU) to achieve real-time performance. Extensive experiments
      demonstrate that our new scheme can effectively protect sensitive identity
      information in surveillance videos and faithfully reconstruct the unblurred video
      stream when both CBP sequences are available. 

PMID- 24136442
TI  - Papilloma development and long-term ciclosporin use in chronic ocular allergy
      with associated keratoconus.
AB  - PURPOSE: Conjunctival papillomata are squamous epithelial tumors with a strong
      association with human papilloma virus (HPV) types 6 and 11. They are benign
      conjunctival tumors that can be treated by surgical excision. We report a case
      where topical immunosuppressive therapy modified the local T-cell immunity in the
      conjunctiva resulting in papilloma development in a patient with keratoconus and
      a strong atopic history. METHODS: A case report of a 44-year-old man with a
      history of severe ocular and generalized atopy is presented. We present the
      problems encountered in management of his severe ocular allergy and how these
      impeded the management of his keratoconus. RESULTS: Conventional antiallergy
      topical medication was not producing symptom relief in this patient, and so
      topical immunosuppression was commenced using ciclosporin ointment 0.2%. This
      therapy modified the local T-cell immunity in the conjunctiva resulting in the
      development of papillomata which contributed to the intolerance of contact lens
      wear for visual rehabilitation of the keratoconus in the patient. These lesions
      were surgically removed but typically recurred and required further surgical
      excision. Adjunct cryotherapy was also performed at the time of the surgery to
      try to stem the recurrence of the papillomas. CONCLUSIONS: To the best of our
      knowledge and following a review of the published literature using key databases
      that include Medline and PubMed, this is the first report confirming the
      development of conjunctival papillomas secondary to HPV type 6 in a ciclosporin
      treated patient.

PMID- 24136443
TI  - Plasma-exchange treatment for severe carbamazepine intoxication: a case study.
AB  - Acute poisoning is an important cause of morbidity and mortality during
      childhood. This manuscript reports the positive outcome of a pediatric case with
      a history of accidental carbamazepine intake treated using plasma exchange. A 3
      year-old male presented with severe carbamazepine intoxication. He was comatose
      and had generalized tonic clonic seizure, ventricular tachycardia, and
      hypotension. Although he did not respond to classical therapies, we performed two
      sessions of plasma exchange. The patient recovered rapidly and was discharged
      from the hospital six days from the time of carbamazepine ingestion with no
      complication or neurologic impairment. Plasma exchange can be performed safely in
      very small children, and it might be the first line treatment, particularly for
      intoxication with drugs that have high plasma-protein-binding properties.

PMID- 24136444
TI  - Diversity of rotavirus strains circulating in Northern Brazil after introduction
      of a rotavirus vaccine: high prevalence of G3P[6] genotype.
AB  - Rotavirus A (RVA) is the most common cause of severe acute gastroenteritis in
      infants and young children worldwide, causing 453,000 deaths annually. In Brazil,
      the most frequent genotype identified was G1 during almost three decades in the
      pre-vaccination period; however, after anti-rotavirus vaccine introduction, there
      was a predominance of G2 genotype. The aim of this study was to determine the G
      and P genotypes of rotaviruses isolated from children under 5 years of age with
      acute gastroenteritis in the Northern region of Brazil, and discuss the emergence
      of G3P[6] genotype. A total of 783 stool specimens were obtained between January
      2011 and March 2012. RVA antigen was detected in 33% (272/783) of samples using a
      commercial enzyme-linked immunosorbent assay and type-specificity was determined
      by reverse-transcription polymerase chain reaction. The most common binary
      combination was G2P[4], representing 41% of cases, followed by G3P[6] (15%),
      G1P[8] (8%), G3P[8] (4%), G9P[8] (3%), and G12P[6] (2%). G3P[6] strains were
      analyzed further and phylogenetic analysis of VP7 gene showed that G3 strains
      clustered into lineage I and showed a high degree of amino acid identity with
      vaccine strain RV3 (95.1-95.6%). For VP4 sequences, G3P[6] clustered into lineage
      Ia. It was demonstrated by the first time the emergence of unusual genotype
      G3P[6] in the Amazon region of Brazil. This genotype shares neither VP7 nor VP4
      specificity with the used vaccine and may represent a challenge to vaccination
      strategies. A continuous monitoring of circulating strains is therefore needed
      during the post-vaccine era in Brazil.

PMID- 24136445
TI  - Comparison between posterior lumbar interbody fusion and posterolateral fusion
      with transpedicular screw fixation for isthmic spondylolithesis: a meta-analysis.
AB  - INTRODUCTION: Primary aim of this study was to compare long-term pain relief and
      quality of life in adults with isthmic spondylolisthesis (IS) who were treated
      with posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF).
      Secondary aim was to compare the fusion and infection rates of PLIF- or PLF
      treated groups. MATERIALS AND METHODS: We searched four databases and the cited
      reference lists of the included studies. Inclusion criteria were pain assessment
      with visual analog scale (VAS), and clinical studies that compared long-term pain
      relief of PLF and PLIF-treated adults with IS. Exclusion criteria were use of
      only one treatment and non-English language. RESULTS: Three of five included
      studies used VAS to assess the decline in low back pain, radicular pain, or leg
      pains in PLF- or PLIF-treated patients during the follow-up periods (0.5-6
      years). Long-term pain relief significantly improved in both treatment groups.
      Pooled differences in mean improvement of Oswestry disability index after the
      operation revealed no significant difference in pain relief between the PLF and
      PLIF groups (P = 0.856). The five studies together indicated that fusion rate was
      significantly greater in the PLIF group than that in the PLF group. CONCLUSIONS:
      The majority of PLIF- and PLF-treated adults with low-grade IS experienced long
      term pain relief to a similar extent in most studies. PLIF treatment provided
      significantly better fusion rates than PLF treatment. This meta-analysis
      indicates that the use of separate, well-defined scales for pain relief and
      functional outcomes are needed in studies of PLF or PLIF-treated patients.

PMID- 24136446
TI  - Robotic surgery for primary head and neck squamous cell carcinoma of unknown
      site.
AB  - IMPORTANCE: Identification of the primary site in head and neck squamous cell
      carcinoma (HNSCC) is crucial because it improves the patient's prognosis and
      minimizes morbidity from treatment. OBJECTIVES: To determine the efficacy of
      transoral robotic surgery (TORS) in identifying unknown primary sites of head and
      neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective,
      multi-institutional case series from January 1, 2010, to February 28, 2013, in
      which data were pooled from the following 6 institutions: University of
      Washington Medical Center, The University of Texas MD Anderson Cancer Center,
      University of Alabama-Birmingham Hospital, The University of Texas Medical School
      at Houston, Johns Hopkins Hospital, and Oregon Health Sciences University. All
      patients diagnosed as having HNSCC of an unknown primary site who underwent TORS
      to identify the primary site were included in the study. We excluded those with
      recurrent disease, a history of radiation therapy to the head and neck, or
      evidence of a primary tumor site based on previous biopsy results. MAIN OUTCOME
      AND MEASURE: Identification of the primary tumor site. RESULTS: Forty-seven
      patients were eligible for the study. The tumor site was identified by TORS in 34
      of 47 patients (72.3%). The primary site was located in the base of tongue for 20
      patients (58.8%) and the palatine tonsil for 13 patients (38.2%), with 1 patient
      having a primary site in both the base of tongue and the palatine tonsil.
      Suspicious physical examination findings were present in 23 of 47 patients
      (48.9%), with positive and negative predictive values of 56.5% and 25.0%,
      respectively. Of those who underwent any imaging, 16 patients had suspicious
      findings, with positive and negative predictive values of 50.0% and 16.7%,
      respectively. In 18 of 47 patients (38.3%), both preoperative radiographic and
      physical examination failed to suggest a primary site. Of these 18 patients, 13
      (72.2%) were identified after undergoing TORS. CONCLUSIONS AND RELEVANCE: We
      demonstrate that TORS is a useful approach to identify and treat the primary site
      in patients with HNSCC who present with an unknown primary site.

PMID- 24136447
TI  - Enhanced frequency response of a highly transparent PVDF-graphene based thin film
      acoustic actuator.
AB  - A high-performance polyvinylidene fluoride (PVDF) based thin film acoustic
      actuator with chemical vapor deposition (CVD) graphene electrodes was
      successfully fabricated. Importantly, it showed 60, 19, and 22% enhancement in
      the bass, middle and treble frequency response, respectively. 

PMID- 24136448
TI  - Age and task difficulty differences in dual tasking using circle tracing and
      serial subtraction tasks.
AB  - The aim of this study was to investigate age-related differences in dual task
      performance by using an upper limb proprioceptive task. Twenty-eight younger (18
      30 years) and 28 older (>60 years) healthy adults performed circle tracing and
      serial subtraction tasks separately and concurrently. The tasks had two levels of
      difficulty: easy and hard. The circle tracing task included direct (easy) and
      indirect (hard) visual feedback conditions, and it was paired with serial
      subtraction by twos (easy) or threes (hard). We found that older adults were
      significantly slower than younger adults across all conditions and had
      significantly greater dual task costs when they performed circle tracing with
      easy serial subtraction. Higher levels of task difficulty were associated with
      slower speed in both groups. We found no age differences in accuracy.
      Participants either traded speed for accuracy or accuracy for speed regardless of
      age group. Overall, the findings suggest that speed and accuracy may be affected
      differently during dual tasking. In addition, older adults may rely more
      extensively on proprioceptive feedback to guide upper limb movement compared with
      younger adults. 

PMID- 24136449
TI  - Characteristics of the personal and environmental components of person
      environment fit in very old age: a comparison between people with self-reported
      Parkinson's disease and matched controls.
AB  - BACKGROUND AND AIMS: To investigate differences and similarities in person
      environment (P-E) fit problems between very old people with self-reported
      Parkinson's disease (PD) and matched controls. METHODS: Data collected for the
      cross-national ENABLE-AGE Survey Study were used to identify people with self
      reported PD (n = 20), and to select three matched controls per individual (n =
      60). The matching criteria were age (mean = 82 years), sex, country, and type of
      housing. The data analysis targeted P-E fit (i.e. accessibility) problems,
      including studying the personal and environmental components separately. The
      personal component was analyzed in terms of functional limitations, and the
      environmental component in terms of physical environmental barriers. RESULTS: In
      comparison to the matched controls, the participants with PD had more functional
      limitations, used more mobility devices and were subjected to more P-E fit
      problems, though the number of environmental barriers did not differ from the
      controls. In the PD sample, P-E fit problems were significantly stronger
      associated with poor balance and incoordination, and the environmental barriers
      that generated the most severe P-E fit problems were more often located to the
      exterior surroundings of the housing compared to the controls. CONCLUSIONS: The
      novel contribution of this explorative study is the demonstration of the type of
      knowledge that can be generated by unfolding and comparing the composition of P-E
      fit (accessibility) problems among people with self-reported PD as compared with
      matched controls. The knowledge thereby generated can be used to develop more
      targeted rehabilitation approaches, efficient housing adaptation services and
      societal planning for people with neurodegenerative disorders.

PMID- 24136451
TI  - The branching pattern of the aortic arch in the long-legged buzzard (Buteo
      rufinus Cretzschmar 1829).
AB  - The aim of this study was to investigate the vascular branching morphology of the
      aortic arch in the long-legged buzzard. For this purpose, two long-legged
      buzzards were evaluated in this study. The latex injection method was used to
      investigate the branching of the aortic arch. Two innominate brachiocephalic
      trunks branched continually from aortic arch caudoventral to the primary bronchi
      and ventral to the syrinx. The left subclavian artery gave rise to
      sternoclavicular, thoracic, axillary and intercostal arteries in this region. On
      the right side, it was observed that the right subclavian artery gave off
      thoracic, sternoclavicular and intercostal arteries, and the axillary artery was
      the branch of thoracic artery differently from the left one. Each carotid artery
      was continued to the middle of the neck and soon disappeared, becoming covered by
      the muscles of the anterior part of the neck, and entering the canal formed by
      the inferior spinous processes of the cervical vertebrae, within which it ran
      hidden, and in close contact with its fellow of the other lateral side, to near
      the head. This morphological study in the long-legged buzzard will elucidate the
      vascular organization for regional blood supply, and provide specific anatomical
      data. 

PMID- 24136450
TI  - UXT is a novel regulatory factor of regulatory T cells associated with Foxp3.
AB  - Regulatory T (Treg) cells are a constitutively immunosuppressive subtype of T
      cells that contribute to the maintenance of immunological self-tolerance and
      immune homeostasis. However, the molecular mechanisms involved in the regulation
      of Treg cells remain unclear. In the present study, we identified ubiquitously
      expressed transcript (UXT) to be a novel regulator of human Treg-cell function.
      In cultured human Treg cells, UXT associates with Foxp3 in the nucleus by
      interacting with the proline-rich domain in the N-terminus of Foxp3. Knockdown of
      UXT expression in Treg cells results in a less-suppressive phenotype,
      demonstrating that UXT is an important regulator of the suppressive actions of
      Treg cells. Depletion of UXT affects the localization stability of Foxp3 protein
      in the nucleus and downregulates the expression of Foxp3-related genes. Overall,
      our results show that UXT is a cofactor of Foxp3 and an important player in Treg
      cell function. 

PMID- 24136452
TI  - Racial and ethnic disparities in future testing intentions for HIV: United
      States, 2007-2010: results from the National Health Interview Survey.
AB  - This study examined racial/ethnic differences in rationale for intending to test
      for HIV. Data were analyzed from 98,971 adults from the 2007-2010 National Health
      Interview Survey. An estimated 38.5 % of respondents previously tested for HIV.
      Testing as part of a medical checkup or procedure was the most common reason for
      being tested among studied racial/ethnic groups. Non-Hispanic whites (80.7 %) and
      non-Hispanic Asians (71.2 %) had higher proportions (p < 0.001) of respondents
      that have not been tested for HIV due to believing they were unlikely exposed.
      Non-Hispanic blacks (ARR: 2.55; 95 % CI 2.39-2.72) and Hispanics (ARR: 1.81; 95 %
      CI 1.68-1.95) who ever tested for HIV were significantly more likely to report
      positive future testing intentions compared to non-Hispanic whites. Additional
      efforts to increase the availability of HIV tests by making HIV testing a routine
      part of medical care and increasing knowledge of HIV transmission, risk
      perception, and treatment may reduce racial/ethnic disparities in HIV testing.

PMID- 24136453
TI  - Biosynthesis of silver nanoparticles from deep sea bacterium Pseudomonas
      aeruginosa JQ989348 for antimicrobial, antibiofilm, and cytotoxic activity.
AB  - Pseudomonas aeruginosa (JQ989348) was isolated from deep sea water sample and
      used for synthesis of silver nanoparticles (AgNPs). AgNPs were confirmed by
      analyzing surface plasmon resonance using UV-visible spectrophotometer at 420 nm.
      Further scanning electron microscope analysis confirmed the range of particle
      size between 13 and 76 nm and XRD pattern authorizes the anisotropic crystalline
      nature of AgNPs. Fourier transform infrared spectrum endorsed the presence of
      high amount of proteins and other secondary metabolites in synthesized AgNPs
      influence the reduction process and stabilization of nanoparticles. The
      inhibitory activity of AgNPs was tested against human pathogens showed high
      activity against Eschericia coli, Vibrio cholerae, Aeromonas sp., and
      Cornebacterium sp. demonstrating its antimicrobial value against pathogenic
      diseases. Additionally, biologically synthesized AgNPs have notable anti-biofilm
      activity against primary biofilm forming bacteria P. aeruginosa and
      Staphylococcus aureus. The MTT assay method was evaluated using human cervical
      cancer cells exposed the AgNPs have excellent cytotoxic activity. 

PMID- 24136454
TI  - Posterior cortical atrophy: review of the recent literature.
AB  - Posterior cortical atrophy (PCA) is a group of neurodegenerative dementing
      disorders characterized by initial predominant visual complaints followed by
      progressive decline in cognitive functions. The visuospatial and visuoperceptual
      defects arise from the dysfunction of, respectively, the dorsal (occipito
      parietal) and the ventral (occipito-temporal) streams. Clinical symptoms, results
      of neuropsychological examination, and findings of posterior cerebral atrophy
      and/or posterior hypoperfusion/hypometabolism contribute to the diagnosis.
      However, owing to the insidious onset of PCA and the non-specificity of initial
      symptoms, the diagnosis is often delayed. Specific etiologies include Alzheimer's
      disease, dementia with Lewy bodies, subcortical gliosis, corticobasal
      degeneration, and prion-associated diseases. Alzheimer's disease accounts for at
      least 80 % of PCA cases. Recent research has concentrated on better defining the
      clinical presentation of PCA, improving neuroimaging analysis, testing new
      neuroimaging techniques, and developing biological measurements. Selected recent
      papers on PCA are reviewed in this article.

PMID- 24136455
TI  - Chronic traumatic encephalopathy: where are we and where are we going?
AB  - Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia
      pugilistica) has a rich history in the medical literature in association with
      boxing, but has only recently been recognized with other contact sports, such as
      football and ice hockey, as well as with military blast injuries. CTE is thought
      to be a neurodegenerative disease associated with repeated concussive and
      subconcussive blows to the head. There is characteristic gross and microscopic
      pathology found in the brain, including frontal and temporal atrophy, axonal
      degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43
      pathology. Clinically, there are characteristic progressive deficits in cognition
      (memory, executive dysfunction), behavior (explosivity, aggression), mood
      (depression, suicidality), and motor function (parkinsonism), which correlate
      with the anatomic distribution of brain pathology. While CTE shares clinical and
      neuropathological traits with other neurodegenerative diseases, the clinical
      syndrome and the neuropathology as a whole are distinct from other
      neurodegenerative diseases. Here we review the CTE literature to date. We also
      draw on the literature from mild traumatic brain injury and other
      neurodegenerative dementias, particularly when these studies provide guidance for
      future CTE research. We conclude by suggesting seven essential areas for future
      CTE research. 

PMID- 24136456
TI  - Progressive multifocal leukoencephalopathy in multiple sclerosis.
AB  - AIDS generated a significantly increased interest in the pathogenesis, clinical
      manifestations, and treatment of progressive multifocal leukoencephalopathy
      (PML), a disease previously considered to be very rare. Scrutiny increased after
      a second wave of PML following the introduction of biological agents, in
      particular, natalizumab and efalizumab. While efalizumab, a lymphocyte function
      associated antigen 1 inhibitor marketed for use in psoriasis, has been removed
      from the market, natalizumab, an alpha4beta1 and alpha4beta7 integrin inhibitor,
      remains widely used in the treatment of multiple sclerosis (MS). Approximately
      400 cases of natalizumab-associated PML have been reported from 2005 to August
      2013. Additionally, other therapies currently employed or under development for
      the treatment of MS may also be associated with PML, such as mycophenolate
      mofetil, rituximab, and alemtuzumab. Therefore, practitioners using these
      medications need to understand the risks associated with these agents, ways to
      mitigate the risk, and treatment of PML and the related condition PML immune
      reconstitution inflammatory syndrome. PML associated with the use of therapeutic
      agents, especially, natalizumab, does share similarities with HIV-related PML;
      however, distinct differences exist. Radiographically isolated PML is seen more
      commonly with natalizumab-associated PML and the disease appears to be heralded
      more often by cognitive and behavior disturbances. Furthermore, the mortality of
      natalizumab-associated PML is substantially lower. Risk mitigation strategies
      have been developed for the natalizumab-associated PML, which has been
      convincingly demonstrated to be linked to duration of therapy, JC virus
      seropositivity, and the prior use of immunosuppressive agents. 

PMID- 24136457
TI  - Genetics in dystonia: an update.
AB  - The past year has been extremely successful with regard to the genetics of
      dystonia, with the identification of four new dystonia genes (CIZ1, ANO3, GNAL,
      and TUBB4A). This progress was primarily achieved because of the application of a
      new technology, next-generation DNA sequencing, which allows rapid and
      comprehensive assessment of a patient's genome. In addition, a combination of
      next-generation and traditional Sanger sequencing has expanded the phenotypic
      spectrum associated with some of the dystonia plus (ATP1A3) and paroxysmal
      (PRRT2) loci. This article reviews the newly identified genes and phenotypes and
      discusses the future applications of next-generation sequencing to dystonia
      research. 

PMID- 24136458
TI  - Neuroimaging as a window into gait disturbances and freezing of gait in patients
      with Parkinson's disease.
AB  - Neuroimaging has been applied to better understand the neural mechanisms
      underlying gait disturbances in Parkinson's disease (PD). In the present paper,
      we review studies that used neuroimaging methods to investigate mobility, walking
      and freezing of gait (FOG) in PD, focusing on the recent literature. Examination
      of these studies suggests that gait changes in PD are due to widespread
      alterations in the structure and function of the brain that go beyond the basal
      ganglia. For example, cortical structures including the frontal and parietal
      lobes, the mesencephalic locomotor region and specifically, the pedunculopontine
      nucleus, all apparently play important roles in the control of gait in PD.
      Nonetheless, there are some significant inconsistencies across the different
      studies and many questions remain regarding the precise pathological processes
      that contribute to gait disturbances, in general, and to FOG, more specifically.
      A discussion of new insights into the neural mechanisms underlying gait
      disturbances are presented along with a summary of the disadvantages and
      limitations of the existing techniques and suggestions for future directions. 

PMID- 24136459
TI  - Amyloid imaging in atypical presentations of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is thought to progress in a fairly stereotyped manner,
      with episodic memory loss being the first and most salient domain of impairment,
      reflecting the early disease in structures supporting this function. However,
      there is considerable heterogeneity in the relative involvement of different
      cognitive domains, and at the extreme are three syndromes associated with AD: (1)
      logopenic progressive aphasia, (2) posterior cortical atrophy, and (3) frontal
      variant of AD. As each of these syndromes is variably associated with non-AD
      dementia and clinically overlaps with other presentations more commonly
      associated with different causes of neurodegeneration (e.g., progressive
      nonfluent aphasia), the use of amyloid imaging for detection of the molecular
      pathologic features of AD is of significant clinical value. This article reviews
      several amyloid imaging studies of these populations which support autopsy case
      series and reveal a dissociation between the spatial distribution of amyloid
      plaques and clinical phenotype. 

PMID- 24136460
TI  - Anti-tumor activity of the X-linked inhibitor of apoptosis (XIAP) inhibitor
      embelin in gastric cancer cells.
AB  - This study investigated the anticancer effects of embelin in human gastric cancer
      cells and the underlying molecular mechanisms. Gastric cancer cells were treated
      with embelin and 5-FU for methyl-thiazolyl-tetrazolium bromide cell viability
      assay and flow cytometric detection of cell viability and apoptosis. Protein
      pathway array (PPA) and Western blot were used to investigate differentially
      expressed proteins in embelin-treated gastric cancer cells. Embelin reduced
      gastric cancer cell viability, induced apoptosis, and enhanced 5-FU antitumor
      activity in gastric cancer cells. Mechanistically, embelin induced cell cycle
      arrest at the S and G2/M phases. Molecularly, embelin downregulated expression of
      X-linked inhibitor of apoptosis and cell cycle-regulatory proteins, such as CDK1,
      CDC25B, CDC25C, cyclinB1, and CDK2. PPA analysis showed that embelin modulated
      several pathways that are associated with cell growth and apoptosis, such as
      PI3K/AKT, JAK/STAT, p38 MAPK, and p53. The data from the current study implied
      that reduction of gastric cancer cell viability after treatment with embelin was
      through cell cycle arrest at the S and G2/M phases and apoptosis. 

PMID- 24136463
TI  - Morphological and quantitative evaluation of the ovarian recrudescence in Nile
      tilapia (Oreochromis niloticus) after spawning in captivity.
AB  - The Nile tilapia is one of the most important fish species for aquaculture
      worldwide. Understanding their reproductive biology is essential for improving
      their aquaculture methods. The morphological and quantitative dynamics of ovarian
      recrudescence of Oreochromis niloticus was studied for 21 days postspawning. To
      accomplish this, breeding females were kept in controlled conditions and ovarian
      samples were collected weekly for histological, ultrastructural and morphometric
      analyses. Ovarian follicle morphology revealed an intense synthesis activity of
      the follicular cells, which actively contributed to formation of the zona radiata
      and oocyte development following spawning. Recently spawned ovaries contained
      follicles at all developmental stages, but they were predominantly early primary
      growth (~ 42%) and full-grown follicles (~ 20%). Remnants of spawning,
      postovulatory follicle complexes represented approximately 5% of the former
      ovarian follicles immediately after spawning, and less than 1% after 7 days.
      Atretic follicles accounted for approximately 2% of the follicles studied during
      the period. The stock of primary growth follicles was stable during ovarian
      recrudescence, indicating their availability for continuous recruitment. Only the
      frequency of full-grown follicles significantly increased in the ovaries during
      recrudescence, representing approximately 35% of the follicles 21 days
      postspawning. The diameters of all follicles were significantly different between
      the periods analyzed. The ovaries' morphological characteristics, the maintenance
      of young follicles stocks and the gradual and significant increase in the
      proportion and diameter of full-grown follicles showed a rapid ovarian recovery
      and follicular growth of O. niloticus, in 21 days at 29.5 degrees C, necessary
      for the next spawning.

PMID- 24136461
TI  - Novel mechanism regulating endothelial permeability via T-cadherin-dependent VE
      cadherin phosphorylation and clathrin-mediated endocytosis.
AB  - T-cadherin is a unique member of the cadherin superfamily of adhesion molecules.
      In contrast to "classical" cadherins, T-cadherin lacks transmembrane and
      cytoplasmic domains and is anchored to the cell membrane via a
      glycosilphosphoinositol moiety. T-cadherin is predominantly expressed in
      cardiovascular system. Clinical and biochemical studies evidence that expression
      of T-cadherin increases in post-angioplasty restenosis and atherosclerotic
      lesions-conditions associated with endothelial dysfunction and pathological
      expression of adhesion molecules. Here, we provide data suggesting a new
      signaling mechanism by which T-cadherin regulates endothelial permeability. T
      cadherin overexpression leads to VE-cadherin phosphorylation on Y731 (beta
      catenin-binding site), VE-cadherin clathrin-dependent endocytosis and its
      degradation in lysosomes. Moreover, T-cadherin overexpression results in
      activation of Rho GTPases signaling and actin stress fiber formation. Thus, T
      cadherin up-regulation is involved in degradation of a key endothelial adhesion
      molecule, VE-cadherin, resulting in the disruption of endothelial barrier
      function. Our results point to the role of T-cadherin in regulation of
      endothelial permeability and its possible engagement in endothelial dysfunction. 

PMID- 24136465
TI  - Evolution of nickel sulfide hollow spheres through topotactic transformation.
AB  - In this study, a topotactic transformation route was proposed to synthesize
      single-crystalline beta-NiS hollow spheres with uniform phase and morphology
      evolving from polycrystalline alpha-NiS hollow spheres. Uniform polycrystalline
      alpha-NiS hollow spheres were firstly prepared with thiourea and glutathione as
      sulfur sources under hydrothermal conditions through the Kirkendall effect. By
      increasing the reaction temperature the polycrystalline alpha-NiS hollow spheres
      were transformed to uniform beta-NiS hollow spheres. The beta-NiS crystals
      obtained through the topotactic transformation route not only have unchanged
      morphology of hollow spheres but are also single-crystalline in nature. The as
      prepared NiS hollow spheres display a good ability to remove the organic
      pollutant Congo red from water, which makes them have application potential in
      water treatment. 

PMID- 24136464
TI  - Targeted resequencing of candidate genes reveals novel variants associated with
      severe Behcet's uveitis.
AB  - Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized
      by four major manifestations: recurrent uveitis, oral and genital ulcers and skin
      lesions. To identify some pathogenic variants associated with severe Behcet's
      uveitis, we used targeted and massively parallel sequencing methods to explore
      the genetic diversity of target regions. A solution-based target enrichment kit
      was designed to capture whole-exonic regions of 132 candidate genes. Using a
      multiplexing strategy, 32 samples from patients with a severe type of Behcet's
      uveitis were sequenced with a Genome Analyzer IIx. We compared the frequency of
      each variant with that of 59 normal Korean controls, and selected five rare and
      eight common single-nucleotide variants as the candidates for a replication
      study. The selected variants were genotyped in 61 cases and 320 controls and, as
      a result, two rare and seven common variants showed significant associations with
      severe Behcet's uveitis (P<0.05). Some of these, including rs199955684 in
      KIR3DL3, rs1801133 in MTHFR, rs1051790 in MICA and rs1051456 in KIR2DL4, were
      predicted to be damaging by either the PolyPhen-2 or SIFT prediction program.
      Variants on FCGR3A (rs396991) and ICAM1 (rs5498) have been previously reported as
      susceptibility loci of this disease, and those on IFNAR1, MTFHR and MICA also
      replicated the previous reports at the gene level. The KIR3DL3 and KIR2DL4 genes
      are novel susceptibility genes that have not been reported in association with
      BD. In conclusion, this study showed that target enrichment and next-generation
      sequencing technologies can provide valuable information on the genetic
      predisposition for Behcet's uveitis. 

PMID- 24136466
TI  - Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in
      acute coronary syndrome patients: cost-effectiveness analyses for six European
      perspectives.
AB  - Platelet reactivity assays (PRAs) can predict patients' likely response to
      clopidogrel. As ticagrelor and prasugrel are typically considered first-line
      agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness
      of universal compared to PRA-driven selection of these agents. A Markov model was
      used to calculate five-year costs (2013L/?), quality-adjusted life-years and
      incremental cost-effectiveness ratios (ICERs) for one-year of universal
      ticagrelor or prasugrel (given to all) compared to each agents' corresponding PRA
      driven strategy (ticagrelor/prasugrel in those with high platelet reactivity
      [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We
      assumed patients had their index event at 65-70 years of age and had a 42.7%
      incidence of HPR 24-48 hours post-revascularisation. The analysis was conducted
      from the perspective of six countries (France, Germany, Italy, Spain, the
      Netherlands and United Kingdom) and used a one-year cycle length. Event data for
      P2Y12 inhibitors were taken from multinational randomised trials and adjusted
      using country-specific epidemiologic data. Neither universal ticagrelor nor
      prasugrel were found to be cost-effective (all ICERs >40,250? or L36,600/QALY)
      compared to their corresponding PRA-driven strategies in any of the countries
      evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and
      drug-specific relative risks of major adverse cardiac events. Monte Carlo
      simulation suggested universal ticagrelor or prasugrel were cost-effective in
      only 25-44% and 11-17% of 10,000 iterations compared to their respective PRA
      driven strategies, when applying a willingness-to-pay threshold = ?30,000 or
      L20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not
      likely cost-effective compared to PRA-driven strategies. 

PMID- 24136467
TI  - Study of the potential of the air lift bioreactor for xylitol production in fed
      batch cultures by Debaryomyces hansenii immobilized in alginate beads.
AB  - Cell immobilization has shown to be especially adequate for xylitol production.
      This work studies the suitability of the air lift bioreactor for xylitol
      production by Debaryomyces hansenii immobilized in Ca-alginate operating in fed
      batch cultures to avoid substrate inhibition. The results showed that the air
      lift bioreactor is an adequate system since the minimum air flow required for
      fluidization was even lower than that leading to the microaerobic conditions that
      trigger xylitol accumulation by this yeast, also maintaining the integrity of the
      alginate beads and the viability of the immobilized cells until 3 months of
      reuses. Maximum productivities and yields of 0.43 g/l/h and 0.71 g/g were
      achieved with a xylose concentration of 60 g/l after each feeding. The xylose
      feeding rate, the air flow, and the biomass concentration at the beginning of the
      fed-batch operation have shown to be critical parameters for achieving high
      productivities and yields. Although a maximum xylitol production of 139 g/l was
      obtained, product inhibition was evidenced in batch experiments, which allowed
      estimating at 200 and 275 g/l the IC50 for xylitol productivity and yield,
      respectively. The remarkable production of glycerol in the absence of glucose was
      noticeable, which could not only be attributed to the osmoregulatory function of
      this polyol in conditions of high osmotic pressure caused by high xylitol
      concentrations but also to the role of the glycerol synthesis pathway in the
      regeneration of NAD(+) in conditions of suboptimal microaeration caused by
      insufficient aeration or high oxygen demand when high biomass concentrations were
      achieved.

PMID- 24136468
TI  - Metabolic engineering for ricinoleic acid production in the oleaginous yeast
      Yarrowia lipolytica.
AB  - Although there are numerous oleochemical applications for ricinoleic acid (RA)
      and its derivatives, their production is limited and subject to various safety
      legislations. In an effort to produce RA from alternative sources, we constructed
      a genetically modified strain of the oleaginous yeast Yarrowia lipolytica. This
      strain is unable to perform beta-oxidation and is invalidated for the native
      triacylglycerol (TAG) acyltransferases (Dga1p, Dga2p, and Lro1p) and the ?12
      desaturase (Fad2p). We also expressed the Ricinus communis ?12 hydroxylase
      (RcFAH12) under the control of the TEF constitutive promoter in this strain.
      However, RA constituted only 7% of the total lipids produced by this modified
      strain. By contrast, expression of the Claviceps purpurea hydroxylase CpFAH12 in
      this background resulted in a strain able to accumulate RA to 29% of total
      lipids, and expression of an additional copy of CpFAH12 drove RA accumulation up
      to 35% of total lipids. The co-expression of the C. purpurea or R. communis type
      II diacylglycerol acyltransferase (RcDGAT2 or CpDGAT2) had negative effects on RA
      accumulation in this yeast, with RA levels dropping to below 14% of total lipids.
      Overexpression of the native Y. lipolytica PDAT acyltransferase (Lro1p) restored
      both TAG accumulation and RA levels. Thus, we describe the consequences of
      rerouting lipid metabolism in this yeast so as to develop a cell factory for RA
      production. The engineered strain is capable of accumulating RA to 43% of its
      total lipids and over 60 mg/g of cell dry weight; this is the most efficient
      production of RA described to date.

PMID- 24136469
TI  - Microbial community and function of enrichment cultures with methane and toluene.
AB  - The interaction effect of co-existence of toluene and CH4 on community and
      activity of methanotrophs and toluene-degrading bacteria was characterized in
      three consortia enriched with CH4 and toluene (MT), toluene (T), and CH4 (M),
      respectively, in this study. The CH4 oxidation activity in the enrichment culture
      of MT was significantly lower than that of M at the end of the experiment (P =
      0.001). The toluene degradation rate could be enhanced by continuous addition of
      CH4 and toluene in the initial days, but it was inhibited in the later days.
      Phylogenetic analysis of 16S rRNA genes showed that Proteobacteria and
      Bacteroidetes were dominant in the three enriched consortia, but the community of
      methanotrophs and toluene-degrading bacteria was significantly affected by the co
      existence of CH4 and toluene. Both Methylosinus (91.8 %) and Methylocystis (8.2
      %) were detected in the enrichment culture of MT, while only Methylocystis
      species were detected in M. The toluene-degrading bacteria including
      Burkholderia, Flavobacteria, Microbacterium, and Azoarcus were all detected in
      the enrichment culture of T. However, only Azoarcus was found in the enrichment
      culture of MT. Significantly higher contents of extracellular polymeric
      substances polysaccharose and protein in the enrichment culture of MT than that
      of T and M suggested that a higher environmental stress occurred in the
      enrichment culture of MT.

PMID- 24136470
TI  - A method to detect and quantify Phaeomoniella chlamydospora and Phaeoacremonium
      aleophilum DNA in grapevine-wood samples.
AB  - Grapevines are sensitive to a wide range of fungal pathogens, including agents
      such as Phaeomoniella chlamydospora and Phaeoacremonium aleophilum that cause
      tracheomycosis. In the present study, a procedure for DNA extraction from
      grapevine woody tissue is first evaluated and shown to be suitable for
      quantitative analysis. Next, a multiplex real-time PCR method targeting the beta
      tubulin gene of the pathogens and the actin gene of plant material is developed
      and its quantitative capability is verified. This protocol was evaluated in
      inoculated grapevine-wood samples and in young vines from a nursery and was found
      to be reliable and highly specific. Results obtained from inoculated cuttings
      show that the fungal colonization process must be considered regardless of the
      wood phenotype. An analysis of samples of young vines from the nursery shows that
      a high rate of contamination occurs at the basis of plants and that this
      contamination is associated with low quantitative values. This finding provides
      evidence that in vine nurseries, these fungi may be efficient soil-borne
      pathogens. 

PMID- 24136471
TI  - Production of aglycone protopanaxatriol from ginseng root extract using
      Dictyoglomus turgidum beta-glycosidase that specifically hydrolyzes the xylose at
      the C-6 position and the glucose in protopanaxatriol-type ginsenosides.
AB  - The hydrolytic activity of a recombinant beta-glycosidase from Dictyoglomus
      turgidum that specifically hydrolyzed the xylose at the C-6 position and the
      glucose in protopanaxatriol (PPT)-type ginsenosides followed the order Rf > Rg1 >
      Re > R1 > Rh1 > R2. The production of aglycone protopanaxatriol (APPT) from
      ginsenoside Rf was optimal at pH 6.0, 80  degrees C, 1 mg ml-1 Rf, and 10.6 U ml
      1 enzyme. Under these conditions, D. turgidum beta-glycosidase converted
      ginsenoside R1 to APPT with a molar conversion yield of 75.6 % and a productivity
      of 15 mg l-1 h-1 after 24 h by the transformation pathway of R1 -> R2 -> Rh1 ->
      APPT, whereas the complete conversion of ginsenosides Rf and Rg1 to APPT was
      achieved with a productivity of 1,515 mg l-1 h-1 after 6.6 h by the pathways of
      Rf -> Rh1 -> APPT and Rg1 -> Rh1 -> APPT, respectively. In addition, D. turgidum
      beta-glycosidase produced 0.54 mg ml-1 APPT from 2.29 mg ml-1 PPT-type
      ginsenosides of Panax ginseng root extract after 24 h, with a molar conversion
      yield of 43.2 % and a productivity of 23 mg l-1 h-1, and 0.62 mg ml-1 APPT from
      1.35 mg ml-1 PPT-type ginsenosides of Panax notoginseng root extract after 20 h,
      with a molar conversion yield of 81.2 % and a productivity of 31 mg l-1 h-1. This
      is the first report on the APPT production from ginseng root extract. Moreover,
      the concentrations, yields, and productivities of APPT achieved in the present
      study are the highest reported to date.

PMID- 24136472
TI  - Genetic engineering of Pseudomonas putida KT2440 for rapid and high-yield
      production of vanillin from ferulic acid.
AB  - Vanillin is one of the most important flavoring agents used today. That is why
      many efforts have been made on biotechnological production from natural abundant
      substrates. In this work, the nonpathogenic Pseudomonas putida strain KT2440 was
      genetically optimized to convert ferulic acid to vanillin. Deletion of the
      vanillin dehydrogenase gene (vdh) was not sufficient to prevent vanillin
      degradation. Additional inactivation of a molybdate transporter, identified by
      transposon mutagenesis, led to a strain incapable to grow on vanillin as sole
      carbon source. The bioconversion was optimized by enhanced chromosomal expression
      of the structural genes for feruloyl-CoA synthetase (fcs) and enoyl-CoA
      hydratase/aldolase (ech) by introduction of the strong tac promoter system.
      Further genetic engineering led to high initial conversion rates and molar
      vanillin yields up to 86% within just 3 h accompanied with very low by-product
      levels. To our knowledge, this represents the highest productivity and molar
      vanillin yield gained with a Pseudomonas strain so far. Together with its high
      tolerance for ferulic acid, the developed, plasmid-free P. putida strain
      represents a promising candidate for the biotechnological production of vanillin.

PMID- 24136473
TI  - Biosorption characteristics of Aspergillus fumigatus for the decolorization of
      triphenylmethane dye acid violet 49.
AB  - This study focuses on the possible use of Aspergillus fumigatus to remove acid
      violet 49 dye (AV49) from aqueous solution. In batch biosorption experiments, the
      highest biosorption efficiency was achieved at pH 3.0, with biosorbent dosage of
      3.0 gL(-1) within about 30 min at 40  degrees C. The Langmuir and Freundlich
      models were able to describe the biosorption equilibrium of AV49 onto fungal
      biomass with maximum dye uptake capacity 136.98 mg g(-1). Biosorption followed a
      pseudo-second-order kinetic model with high correlation coefficients (R (2) >
      0.99), and the biosorption rate constants increased with increasing temperature.
      Thermodynamic parameters indicated that the biosorption process was favorable,
      spontaneous, and endothermic in nature, with insignificant entropy changes.
      Fourier transform infrared spectroscopy strongly supported the presence of
      several functional groups responsible for dye-biosorbent interaction. Fungal
      biomass was regenerated with 0.1 M sodium hydroxide and could be reused a number
      of times without significant loss of biosorption activity. The effective
      decolorization of AV49 in simulated conditions indicated the potential use of
      biomass for the removal of color contaminants from wastewater.

PMID- 24136474
TI  - Wogonin influences vascular permeability via Wnt/beta-catenin pathway.
AB  - Wogonin, a flavone from the root of Scutellaria baicalensis Georgi, has shown
      various biological activities. In our previous study, it was confirmed that
      wogonin could decrease the expression of hypoxia-inducible factor-1alpha (HIF
      1alpha) by affecting its stability under hypoxia. However, it is still unknown
      whether wogonin could influence Wnt/beta-catenin pathway under hypoxia. In this
      study, we found that wogonin disrupted Wnt/beta-catenin signaling and reduced the
      secretion of vascular endothelial growth factor (VEGF, also known as vascular
      permeability factor, VPF), which increased vascular permeability in certain
      diseases. It was found that wogonin suppressed HUVECs hyperactivity and actin
      remodeling induced by hypoxia, inhibited transendothelial cell migration of the
      human breast carcinoma cell MDA-MB-231 and the extravasated Evans in vivo Miles
      vascular permeability assay. Wogonin-treated cells showed a decrease in the
      expression of Wnt protein and its co-receptors, as well as a parallel increase in
      the expression of Axin and GSK-3beta in degradation complex, leading to
      degradation of beta-catenin. In addition, wogonin promoted the binding between
      Axin and beta-catenin, increased ubiquitination of beta-catenin and promoted its
      degradation. Interestingly, wogonin decreased the expression of TCF-1, TCF-3, and
      LEF-1 and inhibited nuclear accumulation of beta-catenin as well as the binding
      of beta-catenin and TCF-1, TCF-3, or LEF-1. All of the above results showed that
      wogonin could inhibit the expression of VEGF, which is an important factor
      regulated by beta-catenin. Taken together, the results suggested that wogonin was
      a potent inhibitor of Wnt/beta-catenin and influenced vascular permeability, and
      this might provide new therapeutics in certain diseases.

PMID- 24136475
TI  - Emergence of two novel norovirus genotype II.4 variants associated with viral
      gastroenteritis in China.
AB  - Noroviruses (NoVs) are the principal cause of epidemic viral gastroenteritis
      worldwide, including industrialized and developing countries. Eight hundred and
      fifty sporadic specimens from hospitalized children with acute gastroenteritis
      and 131 specimens from seven gastroenteritis outbreaks were collected during 2011
      2012 in Jiangsu, China. All specimens were tested for the presence of norovirus
      (NoV) by real time RT-PCR, and in these, 225/850 of sporadic specimens and 76/131
      of outbreak specimens were positive. By sequencing, two novel variants termed
      JS2011/CHN variant and JS2012/CHN variant were found. By complete genome
      sequencing and phylogenetic analysis confirmed that both JS2011/CHN variant and
      JS2012/CHN variant shared more than 98% identity with GII.4 New Orleans/2009/USA
      strain and GII.4 Sydney/2012/AUS. Both of them had mutations in some key sites in
      nucleotide sequence and amino acid sequence of ORF1-ORF3. Whether two novel
      variants will cause epidemic of NoV outbreaks in China deserves further
      attention. A national surveillance network may be needed to identify trends in
      molecular evolution of NoVs for prevention of future epidemics.

PMID- 24136476
TI  - Central-part laryngectomy is a useful and less invasive surgical procedure for
      resolution of intractable aspiration.
AB  - A novel narrow-field laryngectomy procedure known as central-part laryngectomy
      (CPL) for less invasive laryngeal diversion in patients with intractable
      aspiration is introduced. We conducted retrospective case reviews of 15 patients
      who underwent CPL. In this procedure, an area of the glottis including the mid
      part of the thyroid cartilage and cricoid cartilage is removed to separate the
      digestive tract from the air way. The lateral part of the thyroid cartilage, the
      entire hypopharyngeal mucosa and epiglottis are preserved. The superior laryngeal
      vessels and nerve are not invaded. All fifteen patients were relieved of
      aspiration without major complications. In good accordance with cutting of the
      cricopharyngeal muscles and removal of the cricoid cartilage, postoperative
      videofluoroscopy demonstrated smooth passages of barium. Ten of 12 patients who
      had hoped to resume oral food intake became able to do so after CPL and two
      others also achieved partial oral deglutition. CPL is a useful procedure for
      treatment of intractable aspiration and offers considerable advantages over other
      laryngotracheal diversion procedures from the view point of oral food intake. 

PMID- 24136477
TI  - Influences of demographic changes and medical insurance status on tonsillectomy
      and adenoidectomy rates in Korea.
AB  - In Korea, the proportion of the pediatric population is decreasing due to low
      fertility rates and aging of the society. It is hypothesized that this change in
      population structure and medical insurance status may affect rates of elective
      surgeries more significantly than clinical factors. An observational study
      conducted using data from the Health Insurance Review and Assessment Service for
      tonsillectomy and adenoidectomy, with 403,924 registered patients from 2007
      through 2011. We analyzed longitudinal changes in crude and age-adjusted surgery
      rates of three surgeries-tonsillectomy without adenoidectomy (T), adenoidectomy
      without tonsillectomy (A), and tonsillectomy with adenoidectomy (T&A)-according
      to medical insurance status: health insurance (HI) group (better economic status)
      versus health aid (HA) group (poorer economic status). Most of the surgeries
      (51.8 % of T, 93.7 % of A, and 95.1 % of T&A) were performed in patients younger
      than 15. Over 5 years, the proportion of the child population numbers decreased,
      from 17.43 to 15.41 % in the HI group and from 21.20 to 13.15 % in the HA group.
      Thus, crude surgery rates for T, A, and T&A decreased more rapidly in the HA
      group (7.50, 14.79, and 15.55 %) than the HI group (1.69, 1.49, and 0.90 %) each
      year. Adjusted surgery rates for T, A, and T&A increased in the HI group (1.01,
      2.64, and 3.36 %) and decreased in the HA group (1.39, 2.86, and 2.76 %) each
      year. These adjusted surgery rates partially explains the sharper decrease in
      crude surgery rates in the HA group than the HI group. The crude and adjusted
      rates of surgeries were usually higher in lower economic status groups. In
      conclusion, surgery rates were affected by changes in the population structure,
      but by other factors as well. Predictable socioeconomic factors could be used to
      calculate and predict the rates for other well-established surgeries.

PMID- 24136478
TI  - Diagnosis of second primary tumor and long-term survival after single initial
      triple endoscopy in patients with head and neck cancer.
AB  - Patients with squamous cell carcinoma of the upper aerodigestive tract (UADT)
      have a high risk of developing second primary tumors (SPTs). Most of the studies
      concerning triple endoscopy (laryngoscopy, digestive tract endoscopy and
      bronchoscopy) describe the frequency and stage of the SPT, but not its impact on
      survival. This study is a matched pair analysis that included patients with
      squamous cell carcinoma of the UADT who were subjected to a triple endoscopy
      before the first treatment, matched with patients who did not undergo triple
      endoscopy. One hundred and thirty-five patients were included in each group. The
      diagnosis of an SPT was more frequent in the initial triple endoscopy group than
      in the control group (34 and 20 cases, respectively). In the initial triple
      endoscopy group, 50.0 % of these tumors were diagnosed simultaneously, whereas in
      the control, only 5.0 %. No significant differences in the survival rates or in
      clinical stage of the SPTs were found in the two groups. There was no difference
      in the clinical stage of the SPT and the survival rates of the patient groups who
      underwent triple endoscopy at the initial evaluation and those subjected to only
      a routine evaluation and follow-up.

PMID- 24136479
TI  - Conservative management of post-radical prostatectomy incontinence.
AB  - Radical prostatectomy is currently the mainstay of treatment for localized
      prostate cancer. Although there is evidence that the evolution in surgical
      technique with the introduction of laparoscopic and robot-assisted radical
      prostatectomy has resulted in an improvement of functional outcomes, a
      significant percentage of patients are still bothered by post-prostatectomy
      incontinence. However, the majority of patients will find improvement in their
      continence status from conservative measures and a small cohort will require more
      invasive therapeutic options. Conservative treatment includes pelvic floor muscle
      training with or without biofeedback techniques and pharmacotherapy. There is
      evidence that immediate initiation of physiotherapy after surgery will help in
      early restoration of continence, while additional benefit can be provided from
      pharmacotherapy mainly from duloxetine. The present review aims to provide an
      update on the epidemiology of post-prostatectomy incontinence, identify risk
      factors for incontinence after surgery and suggest current trends for
      conservative treatment. 

PMID- 24136480
TI  - [Editorial comment: Conservative management of post-radical prostatectomy
      incontinence].

PMID- 24136481
TI  - Doctor Antonio Alfaro's notes in the treaty by Desault and Bichat. First
      urological work in Spanish in the XIX Century.
AB  - OBJECTIVES: We performed a study on the notes made by doctor Antonio Alfaro to
      the book by Bichat and Desault "Treaty of urinary tract diseases". RESULTS: Such
      notes are altogether more extensive than the work they accompany. In them we see
      the knowledge about the treatment of urinary tract diseases in the beginning of
      the XIX century had a great level and, at least, similar to that of other
      European countries. The notes are accompanied by multiple references to surgeons
      of various times, and publications of that time. All them conform a real Urology
      text with its own personality. CONCLUSIONS: Dr. Antonio Alfaro must be among the
      Spanish urological medical literature authors of the 19th Century.

PMID- 24136482
TI  - Prognostic factors in patients with stage pT0/pT1/pTa in the radical cystectomy
      specimen.
AB  - OBJECTIVES: To identify risk factors for progression in patients with invasive
      bladder carcinoma who were pT0/pT1/pTa after cystectomy. METHODS: We analyzed the
      clinical records of 97 post-cystectomy pT0/pT1/pTa patients for the following
      variables: hydronephrosis, carcinoma in situ (CIS), lymphovascular invasion,
      history of non-muscular invasive disease, residual tumor in the specimen and
      lymphatic invasion (pN). pN+patients were excluded from definitive analysis. The
      quantitative and qualitative variables were analyzed using standard statistics.
      The chi-square test was used to analyze associations between categorical
      variables. Univariate Cox proportional hazard regression analysis (enter method)
      was performed. The Kaplan-Meier method was used to evaluate survival and the log
      rank test to assess differences between groups. Statistical significance was set
      at p<0.05. The analysis was performed using SPSS version 15.0. RESULTS: The study
      sample included 97 cases. The specimen was staged at T2 in 97% of patients after
      transurethral resection (TUR); After cystectomy, the specimen was staged as pT0
      (R0) in 44.3% and pT1/Ta (R1) in 55.7%. Median follow-up was 47 months. Lymph
      node metastasis were detected in 5.2% of patients (pN+rpar; and had a negative
      impact on survival (p=0.02). Overall survival was 59.8% and cancer-specific
      survival 76.6%. Univariate analysis showed a relationship between tumor
      progression and the presence of CIS (p < 0.001), lymphovascular invasion
      (p=0.049), and hydronephrosis(p < 0.001). In the multivariate analysis, only the
      presence of CIS in the transurethral resection was associated with reduced cancer
      specific survival (HR 100.5; 95% CI, 10.8 to 933.1; pp<0.001). CONCLUSIONS:
      Although the prognosis of stage pT0/pT1/pTa carcinoma in the cystectomy specimen
      is excellent, some patients experience progression. The presence of CIS in the
      transurethral resection was an independent predictor of recurrence in these
      cases.

PMID- 24136483
TI  - Radical prostatectomy. Prognostic value of positive surgical margins in pT2
      patients.
AB  - OBJECTIVES: We intend to assess the prognostic influence of surgical margins on
      the biochemical progression free survival (BPFS) in patients classified as pT2
      after radical prostatectomy. METHODS: We analyze a series of 1,132 T1-T2 patients
      with prostate cancer treated with radical prostatectomy between 1989-2009. PT3b,
      pT4 and patients with lymph node involvement were excluded from the series. The
      clinicopathologic variables and the BPFS of pT2(+), pT2(-) and pT3 patients are
      compared. The influential clinicopathologic variables in the BPFS are identified
      in the pT2(+) group and risk groups are designed. RESULTS: Of 1,051 patients
      evaluated finally: 598 (59,6) were pT2(-) 163 (15,5%) pT2(+)80 (7,6%) pT3a(-) and
      210 (20%) pT3(+). Clinical characteristics of pT2(+). It is homogeneous with the
      pT2(-) group and significantly better than pT3(+) group in all the
      clinicopathologic variables evaluated. 5 and 10 year BPFS of the pT2(68 +/- 3%
      and 57 +/- 5%) is significantly worse than pT2( -)(87 +/- 1% and 79 +/- 2%),
      similar to pT3a(-) (75 +/- 5% and 64 +/- 7%and better than pT3(+) (44 +/- 3% and
      (36 +/- 3%) BPFS pT2(+) influential factors: Univariate study : Pathological
      Gleason score 7-10 (HR:2.1 95% IC: 1.1-4.1), (p=0.02)MRI that indicates T3
      (HR:3.2 95%IC: 1.4-7.3), (p=0.04) PSA > 15 ng-ml (HR:4 95% IC: 2-8.2), (p <
      0.0001) and high risk D'Amico group (HR:3.3 95%IC: 1.3-8.5), (p=0.01) are
      influential variables. A risk model with the involved variables can be designed.
      Each variable present is a point. Two groups are designed : Group 1 (0-1
      variable) Group 2 (2-3 variables). 5 and 10 year BPFS for Group 1 are 71+/-5% and
      69 +/- 5%, and are 37 +/- 12% and 22 +/- 11% for Group 2. (p < 0.0001).
      CONCLUSIONS: Surgical margins in pT2 patients have independent influence in the
      BPFS. The group is heterogeneous and it can be divided into two risk groups
      accordingly to the BPFS influential variables: a larger group (86% pT2(+) with
      worse prognosis than pT2(-), and a smaller group (remaining 14%) with similar
      prognosis to pT3 (+).It is likely that pT2(+) patients are a mixture of
      understaged patients with others with iatrogenic margins or false margins due to
      poor assessment of the surgical specimen.

PMID- 24136484
TI  - Post-radical prostatectomy predictive factors for biochemical recurrence.
AB  - OBJECTIVES: To identify post-prostatectomy prognostic factors for biochemical
      recurrence (BR). METHODS: We retrospectively analyze a series of patients with
      clinically localized prostate cancer who were treated with radical prostatectomy
      (RP)as monotherapy between 1996 and 2007, pN0-pNx, with a minimum of 12 months of
      follow-up. BR is considered to be persistence or elevation in PSA after RP
      greater than 0.4 ng/ml on the subsequent determination. Analyzed variables were
      Gleason Score, pathological stage, surgical margin involvement, capsular
      involvement, and perineural involvement. We performed univariate and multivariate
      analysis using the chi squared test and proportional Cox risk model in order to
      determine the variables associated with BR. RESULTS: We included 693 patients.
      Mean age was 63.5 years with a mean follow-up of 88.5 months. Mean PSA was 9.2 ng
      ml. BR was observed in 218 patients, 43 due to biochemical persistence. More
      common pathological findings were Gleason score 7 (47.1%), and pathological stage
      pT2c (60.1%). Mean time to BR was 35.5 months with 91.2% occurring in the first 8
      years. On multivariate analysis, Gleason score >= 7(4+3), pathological stage pT3b
      and positive surgical margin were independent predictors of BR. CONCLUSIONS:
      Gleason Score >= 7(4+3), positive surgical margins and pathological stage pT3 are
      independent prognostic factors associated with BR-free survival.

PMID- 24136485
TI  - Penile metastasis from primary bladder tumour.
AB  - OBJECTIVE: We present a case of cutaneous metastasis caused by a bladder tumor.
      METHODS: 68 year old male, diagnosed with an ISUP high grade urothelial
      carcinoma, affecting the whole bladder wall, including the perivesicular fat and
      macroscopic metastasis in the left ilio-obturator chain (T3N2MO), who presents
      painless induration on the dorsal surface of the glans penis with non-exudative
      ulcerated areas, evolving over several months. Given the negative serology
      result, the lesion was biopsied for anatomopathological study. RESULTS: The
      histopathological study of the lesion corresponded to a cutaneous metastasis from
      high grade urothelial carcinoma. CONCLUSION: Approximately 370 cases of penile
      metastasis have been described and the primary tumor is located in the bladder in
      30-35% of them. Presentation of these lesions is very heterogeneous and requires
      anatomopathological study of the lesion for definitive diagnosis.

PMID- 24136486
TI  - Asymptomatic renocolic fistula as a complication of staghorn calculus: case
      report.
AB  - OBJECTIVE: To report a complication of a staghorn stone in a non-functioning
      right kidney. METHODS: We present a 47 year old female with right lumbar pain and
      history of recurrent urinary tract infection (UTI). After an acute pyelonephritis
      episode, a right staghorn stone was diagnosed in a non-functioning right kidney.
      RESULTS: During right nephrectomy, we found a renocolic fistula not observed in
      the imaging studies before surgery. We performed a simple closure of the colon
      wall after resection of the fistula. CONCLUSION: Asymptomatic renocolic fistula
      is a rare complication of an acute pyelonephritis secondary to a staghorn stone.

PMID- 24136487
TI  - Paraurethral leiomyoma.
AB  - OBJECTIVE: To describe a case of para-urethral leiomyoma and to review the
      literature. METHODS: The usual preoperative diagnostic procedures and clinical
      manifestations are discussed. RESULTS: The mass was resected and, 6 years later,
      the patient remains asymptomatic and with no recurrence. CONCLUSIONS: Urethral or
      paraurethral leiomyomas are benign tumors that arise from the urethral or vaginal
      smooth muscle. Radiological findings (particularly magnetic resonance imaging)
      may suggest the origin of the tumor before surgery; however, the final diagnosis
      is determined by histology.

PMID- 24136488
TI  - Conservative surgery in synchronic bilateral renal carcinoma.
AB  - OBJECTIVE: To describe a case of staged conservative treatment of a synchronic
      bilateral renal tumor, a real surgical challenge. METHODS: 46-year old obese
      female who consulted for fever; bilateral solid masses > 70 mm were detected and
      surgical treatment was offered. RESULTS: Staged conservative treatment consisting
      in selective embolization of both lesions and subsequent surgery was performed.
      Right partial nephrectomy with ipsilateral adrenalectomy was done first, and 90
      days later left partial nephrectomy. Pathology revealed, clear cell carcinomas
      with negative surgical margins in both cases in addition to a right adrenal
      adenoma. After 48 months of follow up, the patient remains free of local or
      systemic disease with normal renal function. CONCLUSIONS: The objective for these
      patients is a complete resection of the tumors and preservation of as much renal
      tissue as possible. Conservative surgery has proven to be an effective therapy to
      achieve both goals in cases of bilateral synchronic renal tumors.

PMID- 24136489
TI  - Vascular abnormalities in horseshoe kidney.
AB  - 50 year old male with history of renal colic presenting to the emergency room
      with left colic pain. On ultrasound horseshoe kidneys were visualized without
      hydronephrosis or stones. CT scan: horseshoe kidney with inferior isthmus, no
      signs of nephrolithiasis or urolithiasis. There are multiple associated vascular
      anomalies (there are at least five right renal arteries and two left, double
      venous return is seen in both hemi-kidneys). 

PMID- 24136490
TI  - Giant angiomyolipoma in the upper pole of the right kidney.

PMID- 24136491
TI  - CdTe quantum dots and YAG hybrid phosphors for white light-emitting diodes.
AB  - CdTe quantum dots, 3.28 nm in size, were synthesized using a one-step method in
      an aqueous medium. The CdTe quantum dots were successfully employed as hybrid
      phosphors for white light-emitting diode (LED) devices by combining them with
      yellow-emitting YAG:Ce phosphor. The color-rendering index value and
      International Commission on illumination coordinates for hybrid phosphor white
      LEDs were 75 and (x = 0.30, y = 0.29), respectively. Compared with conventional
      phosphors, semiconductor quantum dots have larger band gap energy and broader
      absorption features, and can be excited more efficiently by optical pumping
      sources. The results confirmed that the high color-rendering index value of the
      white LED was due to the CdTe quantum dots introduced in the hybrid phosphor
      system.

PMID- 24136493
TI  - Risk factors for percutaneous endoscopic gastrostomy tube placement during
      chemoradiotherapy for oropharyngeal cancer.
AB  - IMPORTANCE: Patients with oropharyngeal squamous cell carcinoma undergoing
      chemoradiotherapy may require percutaneous endoscopic gastrostomy (PEG) tube
      placement because of dehydration or significant weight loss. OBJECTIVES: To
      determine the need for the reactive placement of a PEG tube during
      chemoradiotherapy for oropharyngeal cancer and to identify patient or tumor
      factors associated with reactively requiring the placement of a PEG tube. DESIGN,
      SETTING, AND PARTICIPANTS: Single-institution retrospective review of 297
      patients treated with intensity-modulated radiation therapy and concurrent
      chemotherapy for oropharyngeal squamous cell carcinoma between May 1, 2004, and
      June 30, 2012, with a minimum follow-up period of 3 months. EXPOSURE: Placement
      of a PEG tube. MAIN OUTCOMES AND MEASURES: Logistic regression analysis was used
      to identify independent risk factors associated with symptomatic requirement for
      the reactive placement of a PEG tube. RESULTS: In total, 128 patients did not
      receive a prophylactic PEG tube within 10 days of initiation of
      chemoradiotherapy. Fifteen of 128 patients (11.7%) required the reactive
      placement of a PEG tube during or within 3 months of chemoradiotherapy. The
      median time to PEG tube removal was 3.3 months, and 14 of 15 patients had their
      PEG tube removed at the last follow-up analysis. Independent risk factors for PEG
      tube placement included the following: accelerated irradiation fractionation
      (odds ratio, 4.3; 95% CI, 1.1-16.5; P = .04), a tumor T classification of 3 or
      higher (odds ratio, 3.5; 95% CI, 1.0-11.9; P = .04), a cumulative cisplatin dose
      of 200 mg/m2 or higher (odds ratio, 6.7; 95% CI, 1.2-36.7; P = .03), and a body
      mass index (calculated as weight in kilograms divided by height in meters
      squared) of less than 25 (odds ratio, 5.8; 95% CI, 1.4-23.9; P = .02).
      CONCLUSIONS AND RELEVANCE: Although the overall risk is low, a body mass index of
      less than 25, accelerated irradiation fractionation, a tumor T classification of
      3 or higher, and a cumulative cisplatin dose of 200 mg/m2 or higher are
      associated with symptomatic need for the reactive placement of a PEG tube in
      patients with oropharyngeal cancer.

PMID- 24136492
TI  - Viral load and short-term natural history of type-specific oncogenic human
      papillomavirus infections in a high-risk cohort of midadult women.
AB  - Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly
      detected infections and characterize oncogenic HPV natural history in midadult
      women. From 2007 to 2011, we enrolled 521 25-65-year-old-female online daters and
      followed them triannually with mailed health and sexual behavior questionnaires
      and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic
      HPV positive women were selected for type-specific DNA load testing by real-time
      PCR with adjustment for cellularity. Linear or logistic regression models were
      used to evaluate relationships between viral levels, health and sexual behavior,
      and longitudinal oncogenic HPV detection. Type-specific viral levels were
      borderline significantly higher in oncogenic HPV infections that were prevalent
      versus newly detected (p = 0.092), but levels in newly detected infections were
      higher than in infections redetected after intercurrent negativity (p < 0.001).
      Recent sex partners were not significantly associated with viral levels. Compared
      with prevalent infections detected intermittently, the likelihood of persistent
      (OR = 4.31, 95% CI: 2.20-8.45) or single-time (OR = 1.32, 95% CI: 1.03-1.71)
      detection increased per 1-unit increase in baseline log10 viral load. Viral load
      differences between redetected and newly detected infections suggest a portion of
      new detections were due to new acquisition, although report of recent new sex
      partners (a potential marker of new infection) was not predictive of viral load;
      oncogenic HPV infections in midadult women with new partners likely represent a
      mix of new acquisition and reactivation or intermittent detection of previous
      infection. Intermittent detection was characterized by low viral levels,
      suggesting that intermittent detection of persisting oncogenic HPV infection may
      be of limited clinical significance. 

PMID- 24136494
TI  - Results of 30 reverse shoulder prostheses for revision of failed hemi- or total
      shoulder arthroplasty.
AB  - PURPOSE: Revision surgery for shoulder prosthesis remains a difficult task in
      shoulder surgery. The purpose of this retrospective study was to evaluate the
      clinical and radiological outcomes of a series of 30 reverse shoulder prostheses
      performed as revision of failed hemi- or total shoulder arthroplasty. The most
      relevant technical points in surgery are described, as are other surgical
      options; a rational strategy for the treatment of these patients is proposed.
      MATERIALS AND METHODS: Thirty patients (average age 69.5) were included. Mean
      follow-up was 36.4 months (range 24-100 months). There were 14 patients in group
      1 (Delta III) and 16 in group 2 (Reverse Arrow). RESULTS: A total of 83% were
      satisfied (16 cases) or very satisfied (9 cases), and 17% were disappointed (5
      patients). The mean Constant score increased from a mean of 25-52. The mean score
      for pain improved from 5 (range 0-15) to 13 (range 5-15) (p < 0.001). The mean
      score of strength improved from 1 (range 0-6) to 5 (range 0-10) (p < 0.001). The
      forward elevation changed from a mean of 55 degrees  (range 0-120) to 108 degrees
      (range 40-160) (p < 0.001). There was no significant improvement of external
      rotation at 0 degrees  abduction (range 14 degrees -18 degrees ) or internal
      rotation (range 5-4.63). There were 4 scapular notching. We could not find the
      influence of scapular notching on Constant Score. Complication rate was 26.6%.
      CONCLUSION: Reverse total shoulder arthroplasty prosthesis represents an
      available option in difficult cases of failed hemiarthroplasty or total shoulder
      arthroplasty when the rotator cuff is irreparable and the glenoid bone stock is
      sufficient. LEVEL OF EVIDENCE: Level 4.

PMID- 24136496
TI  - Disease genetics: a Mendelian code for complex disease.

PMID- 24136504
TI  - Small RNAs: RNAs attack!

PMID- 24136505
TI  - Cancer genomics: A panoramic view of cancer.

PMID- 24136508
TI  - "Whirl" in the abdomen: beware.

PMID- 24136509
TI  - Rare cause of neonatal cholestasis.

PMID- 24136506
TI  - Meiotic recombination in mammals: localization and regulation.
AB  - During meiosis, a programmed induction of DNA double-strand breaks (DSBs) leads
      to the exchange of genetic material between homologous chromosomes. These
      exchanges increase genome diversity and are essential for proper chromosome
      segregation at the first meiotic division. Recent findings have highlighted an
      unexpected molecular control of the distribution of meiotic DSBs in mammals by a
      rapidly evolving gene, PR domain-containing 9 (PRDM9), and genome-wide analyses
      have facilitated the characterization of meiotic DSB sites at unprecedented
      resolution. In addition, the identification of new players in DSB repair
      processes has allowed the delineation of recombination pathways that have two
      major outcomes, crossovers and non-crossovers, which have distinct mechanistic
      roles and consequences for genome evolution. 

PMID- 24136510
TI  - Plant proteomics methods and protocols.
AB  - In this first, introductory chapter, it is intended to summarize from a
      methodological point of view the state of the art in plant proteomics, focusing
      on mass spectrometry-based strategies. Thus, this chapter is mainly directed at
      beginners or at those trying to get into the field, rather than at those with
      real experience or a long trajectory in plant proteomics research. The different
      alternative workflows, methods, techniques, and protocols from the experimental
      design to the data analysis will be briefly commented, with cross references to
      previous monographs and reviews, as well as to the rest of the book chapters. The
      difficulty of working with proteins, together with the power, limitations, and
      challenges of the approach will also be briefly discussed.Proteins, as molecular
      entities, and the cell proteome, as a whole, are much more complex than what we
      thought in the past and can be studied in a single experiment. Because of that,
      fractionation and complementary strategies are required for its study. The MS
      analysis of complex samples may result in up to 100,000-peptide spectra that
      cannot be easily analyzed with standard procedures. Therefore, proteomics, more
      than other -omics, needs a dry lab, time, and an effort in data mining.As main
      conclusion, it can be stated that proteomics is in its beginnings. It is starting
      to make important contributions to a proper gene annotation, identification, and
      characterization of gene products or protein species and to the knowledge of
      living organisms, having also an enormous application potential to translational
      research. However, and despite its great potential, and as in any other
      experimental approach, it is far from being a Pandora's Box. In the case of plant
      research, the full potential of proteomics is quite far from being totally
      exploited, and second-, third-, and fourth-generation proteomics techniques are
      still of very limited use. Most of the plant proteomics papers so far published
      belong to the descriptive, subcellular, and comparative proteomics subgroup,
      mainly using a few experimental model systems-those whose genome has been
      sequenced-and being from a biological point of view quite descriptive and
      speculative. From now on we should put more emphasis on the study of
      posttranslational proteomics and interactomics, and move to targeted, hypothesis
      driven approaches. Furthermore, and even more important, we should move to data
      validation through other -omics or classical biochemical strategies, in an
      attempt to get a deeper, real, and more accurate view and understanding of cell
      biology. In the modern Systems Biology concept, proteomics must be considered as
      a part of a global, multidisciplinary approach. Making biological sense of a
      proteomics experiment requires a proper experimental design, data validation,
      interpretation, and publication policy.

PMID- 24136507
TI  - Ecological genomics of local adaptation.
AB  - It is increasingly important to improve our understanding of the genetic basis of
      local adaptation because of its relevance to climate change, crop and animal
      production, and conservation of genetic resources. Phenotypic patterns that are
      generated by spatially varying selection have long been observed, and both
      genetic mapping and field experiments provided initial insights into the genetic
      architecture of adaptive traits. Genomic tools are now allowing genome-wide
      studies, and recent theoretical advances can help to design research strategies
      that combine genomics and field experiments to examine the genetics of local
      adaptation. These advances are also allowing research in non-model species, the
      adaptation patterns of which may differ from those of traditional model species. 

PMID- 24136511
TI  - From proteomics to systems biology: MAPA, MASS WESTERN, PROMEX, and COVAIN as a
      user-oriented platform.
AB  - Genome sequencing and systems biology are revolutionizing life sciences.
      Proteomics emerged as a fundamental technique of this novel research area as it
      is the basis for gene function analysis and modeling of dynamic protein networks.
      Here a complete proteomics platform suited for functional genomics and systems
      biology is presented. The strategy includes MAPA (mass accuracy precursor
      alignment; http://www.univie.ac.at/mosys/software.html ) as a rapid exploratory
      analysis step; MASS WESTERN for targeted proteomics; COVAIN (
      http://www.univie.ac.at/mosys/software.html ) for multivariate statistical
      analysis, data integration, and data mining; and PROMEX (
      http://www.univie.ac.at/mosys/databases.html ) as a database module for
      proteogenomics and proteotypic peptides for targeted analysis. Moreover, the
      presented platform can also be utilized to integrate metabolomics and
      transcriptomics data for the analysis of metabolite-protein-transcript
      correlations and time course analysis using COVAIN. Examples for the integration
      of MAPA and MASS WESTERN data, proteogenomic and metabolic modeling approaches
      for functional genomics, phosphoproteomics by integration of MOAC (metal-oxide
      affinity chromatography) with MAPA, and the integration of metabolomics,
      transcriptomics, proteomics, and physiological data using this platform are
      presented. All software and step-by-step tutorials for data processing and data
      mining can be downloaded from http://www.univie.ac.at/mosys/software.html.

PMID- 24136512
TI  - Plant proteomics: from genome sequencing to proteome databases and repositories.
AB  - Proteomic approaches are useful for the identification of functional proteins.
      These have been enhanced not only by the development of proteomic techniques but
      also in concert with genome sequencing. In this chapter, 30 databases and Web
      sites relating to plant proteomics are reviewed and recent technologies relating
      to data collection and annotation are surveyed. 

PMID- 24136513
TI  - How to use 2D gel electrophoresis in plant proteomics.
AB  - Two-dimensional electrophoresis has nurtured the birth of proteomics. It is
      however no longer the exclusive setup used in proteomics, with the development of
      shotgun proteomics techniques that appear more fancy and fashionable
      nowadays.Nevertheless, 2D gel-based proteomics still has valuable features, and
      sometimes unique ones, which make it often an attractive choice when a proteomics
      strategy must be selected. These features are detailed in this chapter, as is the
      rationale for selecting or not 2D gel-based proteomics as a proteomic strategy. 

PMID- 24136514
TI  - Standardization of data processing and statistical analysis in comparative plant
      proteomics experiment.
AB  - Two-dimensional gel electrophoresis remains the most widely used technique for
      protein separation in plant proteomics experiments. Despite the continuous
      technical advances and improvements in current 2-DE protocols, an adequate and
      correct experimental design and statistical analysis of the data tend to be
      ignored or not properly documented in current literature. Both proper
      experimental design and appropriate statistical analysis are requested in order
      to confidently discuss our results and to conclude from experimental data.In this
      chapter, we describe a model procedure for a correct experimental design and a
      complete statistical analysis of proteomic dataset. Our model procedure covers
      all of the steps in data mining and processing, starting with the data
      preprocessing (transformation, missing value imputation, definition of outliers)
      and univariate statistics (parametric and nonparametric tests), and finishing
      with multivariate statistics (clustering, heat-mapping, PCA, ICA, PLS-DA). 

PMID- 24136515
TI  - The expanding universe of mass analyzer configurations for biological analysis.
AB  - Mass spectrometry (MS) is an analytical technique that measures the mass-to
      charge ratio of electrically charged gas-phase particles. All mass spectrometers
      combine ion formation, mass analysis, and ion detection. Although mass analyzers
      can be regarded as sophisticated devices that manipulate ions in space and time,
      the rich diversity of possible ways to combine ion separation, focusing, and
      detection in dynamic mass spectrometers accounts for the large number of
      instrument designs. A historical perspective of the progress in mass spectrometry
      that since 1965 until today have contributed to position this technique as an
      indispensable tool for biological research has been recently addressed by a
      privileged witness of this golden age of MS (Gelpi J. Mass Spectrom 43:419-435,
      2008; Gelpi J. Mass Spectrom 44:1137-1161, 2008). The aim of this chapter is to
      highlight the view that the operational principles of mass spectrometry can be
      understood by a simple mathematical language, and that an understanding of the
      basic concepts of mass spectrometry is necessary to take the most out of this
      versatile technique.

PMID- 24136516
TI  - A protocol for protein extraction from lipid-rich plant tissues suitable for
      electrophoresis.
AB  - Plant tissues contain high levels of nonprotein contaminants such as lipids,
      phenolic compounds, and polysaccharides among others, which interfere with
      protein extraction and electrophoretic separation. Preparation of good-quality
      protein extracts is a critical issue for successful electrophoretic analysis.
      Here, we describe a three-step method for protein extraction from lipid-rich
      plant tissues, which is suitable for both 1-D and 2-D electrophoresis and is
      compatible with downstream applications. The protocol includes prefractionation,
      filtration, and TCA/acetone precipitation steps prior to protein
      resolubilization.

PMID- 24136517
TI  - Making a protein extract from plant pathogenic fungi for gel- and LC-based
      proteomics.
AB  - Proteomic technologies have become a successful tool to provide relevant
      information on fungal biology. In the case of plant pathogenic fungi, this
      approach would allow a deeper knowledge of the interaction and the biological
      cycle of the pathogen, as well as the identification of pathogenicity and
      virulence factors. These two elements open up new possibilities for crop disease
      diagnosis and environment-friendly crop protection. Phytopathogenic fungi, due to
      its particular cellular characteristics, can be considered as a recalcitrant
      biological material, which makes it difficult to obtain quality protein samples
      for proteomic analysis. This chapter focuses on protein extraction for gel- and
      LC-based proteomics with specific protocols of our current research with Botrytis
      cinerea.

PMID- 24136518
TI  - Plant proteomics methods to reach low-abundance proteins.
AB  - The question of low-abundance proteins from biological tissues is still a major
      issue. Technologies have been devised to improve the situation and in the last
      few years a method based on solid-phase combinatorial peptide ligand libraries
      has been extensively applied to animal extracts. This method has also been
      extended to plant extracts taking advantage of findings from previous experience.
      Detailed methods are described and their pertinence highlighted according to
      various situations of plant sample origin, size of the sample, and analytical
      methods intended to be used for protein identifications. 

PMID- 24136519
TI  - Combination of 2DE and LC for plant proteomics analysis.
AB  - The use of analytical biochemical techniques with different separation properties
      allows us to better understand the proteome. To demonstrate this we have used two
      different methodologies to analyze embryos from a Tunisian cultivar of durum
      wheat (Triticum durum Desf.), variety Oum Rabiaa. We compared conventional 2D
      electrophoresis with liquid-phase chromatography. Our results show that a similar
      number of proteins were detected with both techniques. However, analysis of
      protein resolution at different pH ranges showed significant differences. By
      using a large pH gradient we observed that liquid chromatography presents higher
      resolution at extreme pH, either acidic or basic. Conversely, 2DE is more
      resolutive at intermediate pH (pH 5-6.5). Taking these results in consideration,
      we propose that 2DE and liquid chromatography are complementary methods to
      analyze complex protein extracts and can be used in parallel to acquire a wider
      perspective and a better understanding of the embryo proteome.

PMID- 24136520
TI  - 2DE analysis of forest tree proteins using fluorescent labels and multiplexing.
AB  - Although proteomists working with gel-free methods are considering the gels as
      coming from the past, proteomics based on gels has still a lot of opportunities
      to offer and acquisition of images on which thousands of spots may be resolved is
      still largely performed. Nowadays, two-dimensional electrophoresis remains a
      powerful tool to explore the plant proteome and to unravel changes in protein
      abundance between samples. Some weak points can be pointed out, as for any
      method, as for example the lack of reproducibility, or the detection of low
      abundance proteins. The use of the technique called "difference gel
      electrophoresis" or "DIGE" can help to overcome or at least to reduce these
      inconveniences. DIGE requires the labelling of proteins by fluorochromes prior to
      their separation on 2DE gels. This technique may be applied to a wide array of
      plant stress studies, among others to trees. Accurate quantitative results can
      then be obtained and proteins presenting an interest in the studied stress are
      subsequently subjected to an enzymatic digestion (usually with trypsin) and
      identified using electrospray ionization, matrix-assisted laser
      desorption/ionization-time-of-flight-MS, and/or tandem MS.

PMID- 24136521
TI  - Differential plant proteome analysis by isobaric tags for relative and absolute
      quantitation (iTRAQ).
AB  - Protein relative quantitation is one of the main targets in many proteomic
      experiments. Among the range of techniques available for both top-down and bottom
      up approaches, isobaric tags for relative and absolute quantitation (iTRAQ) have
      gained positions within the top-rank techniques used for this purpose in the
      recent years. Briefly, each iTRAQ reagent consists of three different components:
      a reporter group (with a variable mass in the range of 114-117 amu), a balance
      group, and an amino-reactive group. The isobaric nature of iTRAQ-labeled peptides
      adds a signal to every peptide in the sample which is detectable in both MS and
      MS/MS spectra, thus enhancing the sensitivity of detection. During MS/MS, the
      reporter groups are released as singly charged ions with m/z ratios ranking from
      114 to 117 amu, visible in the low mass region of MS/MS spectra. The iTRAQ
      technology can be used to analyze up to four different samples using the 4-plex
      kit (reporter groups 114-115 amu) or can be scaled up to eight different samples
      using the 8-plex kit (reporter groups 113-121 amu). In this chapter, we focus on
      the experimental procedures typically using 4-plex labeling, including tips
      leading to successful application of iTRAQ technology for the analysis of plant
      protein mixtures.

PMID- 24136522
TI  - Global quantitative proteomics using spectral counting: an inexpensive
      experimental and bioinformatics workflow for deep proteome coverage.
AB  - As the field of proteomics shifts from qualitative identification of protein
      "subfractions" to quantitative comparison of proteins from complex biological
      samples, it is apparent that the number of approaches for quantitation can be
      daunting for the result-oriented biologist. There have been many recent reviews
      on quantitative proteomic approaches, discussing the strengths and limitations of
      each. Unfortunately, there are few detailed methodological descriptions of any
      one of these quantitative approaches. Here we present a detailed bioinformatics
      workflow for one of the simplest, most pervasive quantitative approach-spectral
      counting. The informatics and statistical workflow detailed here includes newly
      available freeware, such as SePro and PatternLab which post-process data
      according to false discovery rate parameters, and statistically model the data to
      detect differences and trends.

PMID- 24136523
TI  - Combining chymotrypsin/trypsin digestion to identify hydrophobic proteins from
      oil bodies.
AB  - Oil bodies, lipid-storage organelles, are stabilized by a number of specific
      proteins. These proteins are very hydrophobic, which complicates their
      identification by "classical" proteomic protocols using trypsin digestion. Due to
      the lack of trypsin cleavage sites, the achievable protein coverage is limited or
      even insufficient for reliable protein identification. To identify such proteins
      and to enhance their coverage, we introduced a modified method comprising
      standard three-step procedure (SDS-PAGE, in-gel digestion, and LC-MS/MS
      analysis). In this method, chymotrypsin, single or in combination with trypsin,
      was used, which enabled to obtain proteolytic peptides from the hydrophobic
      regions and to identify new oil bodies' proteins. Our method can be easily
      applied to identification of other hydrophobic proteins. 

PMID- 24136524
TI  - Mass Western for absolute quantification of target proteins and considerations
      about the instrument of choice.
AB  - The Mass Western describes the absolute quantification of proteins based on
      stable isotope labeled integral standard peptides and liquid chromatography
      coupled selective reaction monitoring triple quadrupole mass spectrometry (LC
      SRM/MS). Here, we present a detailed workflow including tips and we discuss
      advantages and disadvantages of using different types of MS for absolute
      quantification. 

PMID- 24136525
TI  - Selected reaction monitoring mass spectrometry: a methodology overview.
AB  - Moving past the discovery phase of proteomics, the term targeted proteomics
      combines multiple approaches investigating a certain set of proteins in more
      detail. One such targeted proteomics approach is the combination of liquid
      chromatography and selected or multiple reaction monitoring mass spectrometry
      (SRM, MRM). SRM-MS requires prior knowledge of the fragmentation pattern of
      peptides, as the presence of the analyte in a sample is determined by measuring
      the m/z values of predefined precursor and fragment ions. Using scheduled SRM-MS,
      many analytes can robustly be monitored allowing for high-throughput sample
      analysis of the same set of proteins over many conditions. In this chapter,
      fundaments of SRM-MS are explained as well as an optimized SRM pipeline from
      assay generation to data analyzed.

PMID- 24136526
TI  - Mass spectrometry-based imaging of metabolites and proteins.
AB  - Imaging techniques based on mass spectrometry (MS) have become powerful
      approaches to decipher the spatial distribution of metabolites and proteins. MS
      imaging (MSI) mostly relies on matrix-assisted laser desorption/ionization
      coupled to MS detection, but desorption electrospray ionization is also
      frequently used. Here we describe our current protocols for MALDI-MSI of seed
      sections and for root tissue. Detailed procedures for cryo-sectioning, matrix
      application, image capture, mass spectrometry measurement and data analysis are
      given. 

PMID- 24136527
TI  - Using the yeast two-hybrid system to identify protein-protein interactions.
AB  - The yeast two-hybrid system is currently one of the most standardized protein
      interaction mapping techniques. The rationale of the yeast two-hybrid system
      relies on the physical separation of the DNA-binding domain from the
      transcriptional activation domain of several transcription factors. The protein
      of interest (bait) is fused to a DNA-binding domain, and complementary DNA (cDNA)
      library-encoded proteins are fused to a transcriptional activation domain. When a
      protein encoded by the cDNA library binds to the bait, both activities of the
      transcription factor are rejoined resulting in transcription from a reporter
      gene. Here, we describe protocols to test interactions between two individual
      proteins and to look for novel interacting partners by screening a single protein
      or domain against a library of other proteins using a GAL4 based yeast two-hybrid
      system. 

PMID- 24136528
TI  - Modifications of wheat germ cell-free system for functional proteomics of plant
      membrane proteins.
AB  - Functional proteomics of plant membrane proteins is an important approach to
      understand the comprehensive architecture of each metabolic pathway in plants.
      One bottleneck in the characterization of membrane proteins is the difficulty in
      producing sufficient quantities of functional protein for analysis. Here, we
      describe three methods for membrane protein production utilizing a wheat germ
      cell-free protein expression system. Owing to the open nature of cell-free
      synthesis reaction, protein synthesis can be modified with components necessary
      to produce functional protein. In this way we have developed modifications to a
      wheat germ cell-free system for the production of functional membrane proteins.
      Supplementation of liposomes or detergents allows the synthesis of functional
      integral membrane proteins. Furthermore, supplementation of myristic acid enables
      synthesis of N-myristylated peripheral membrane proteins. These modified cell
      free synthesis methods facilitate the preparation and subsequent functional
      analyses of a wide variety of membrane proteins.

PMID- 24136529
TI  - Arabidopsis proteomics: a simple and standardizable workflow for quantitative
      proteome characterization.
AB  - Arabidopsis is the model plant of choice for large-scale proteome analyses,
      because its genome is well annotated, essentially free of sequencing errors, and
      relatively small with little redundancy. Furthermore, most Arabidopsis organs are
      susceptible to standard protein solubilization protocols making protein
      extraction relatively simple. Many different facets of functional plant
      proteomics were established with Arabidopsis such as mapping the subcellular
      proteomes of organelles, proteo-genomic peptide mapping, and numerous studies on
      the dynamic changes in protein modification and protein abundances. As most
      standard proteomics technologies are now routinely applied, research interest is
      increasingly shifting towards the reverse genetic characterization of gene
      function at the proteome level, i.e., by profiling the quantitative proteome of
      wild type in comparison with mutant plant tissue. We report here a simple,
      standardizable protocol for the large-scale comparative quantitative proteome
      characterization of different Arabidopsis organs based on normalized spectral
      counting and suggest a statistical framework for data interpretation. Based on
      existing organellar proteome maps, proteins can be assigned to organelles, thus
      allowing the identification of organelle-specific responses.

PMID- 24136530
TI  - Analysis of rice proteins using SDS-PAGE shotgun proteomics.
AB  - In this chapter we describe the workflow used in our laboratory to analyze rice
      leaf samples using label-free shotgun proteomics based on SDS-PAGE fractionation
      of proteins. Rice proteomics has benefitted substantially from successful
      execution of shotgun proteomics techniques. We describe steps on how to proceed
      starting from rice protein extraction, SDS-PAGE, in-gel protein digestion with
      trypsin, nanoLC-MS/MS, and database searching using the GPM. Data from these
      experiments can be used for spectral counting, where simultaneous quantitation of
      several thousand proteins can be obtained.

PMID- 24136531
TI  - Medicago truncatula proteomics for systems biology: novel rapid shotgun LC-MS
      approach for relative quantification based on full-scan selective peptide
      extraction (Selpex).
AB  - Medicago truncatula has become the focus of systems biology research for improved
      legume crop breeding. In plant systems biology, several comparative studies have
      been carried out using liquid chromatography shotgun mass spectrometry (LC-MS/MS)
      and database-dependent protein identification analyses in combination with the
      spectral count for relative quantification. In order to receive optimal protein
      identification rates and spectral count quantification, data-dependent tandem
      mass spectrometry with LC separation of more than 1 h is required. Thus LC-MS/MS
      analyses time is the bottleneck for high-throughput research of experiments with
      high sample number.We describe a novel method, called full-scan (FS) selective
      peptide extraction, that allows for comparative quantification of target peptides
      combined with a significant reduction in LC-MS analysis time. In future, it will
      be a useful tool to detect (15)N-labeled selected peptide patterns for the
      targeted analysis of protein turnover and synthesis. We provide a first reference
      library of selected target peptides generated for M. truncatula leaf tissue.
      These peptides are also suitable candidates for selective reaction monitoring
      approaches. 

PMID- 24136532
TI  - Soybean proteomics.
AB  - Soybean, the world's most widely grown seed legume, is an important global source
      of vegetable oil and protein. Though, complete draft genome sequence of soybean
      is now available, but functional genomics studies remain in their infancy, as
      this agricultural legume species exhibits genetic constrains like genome
      duplications and self-incompatibilities. The techniques of proteomics provide
      much powerful tool for functional analysis of soybean. In the present review, an
      attempt has been made to summarize all significant contributions in the field of
      soybean proteomics. Special emphasis is given to subcellular proteomics in
      response to abiotic stresses for better understanding molecular basis of
      acquisition of stress tolerance mechanism. Detailed protocols of protein
      extraction, solubilization, fractionation of subcellular organelle, and proteins
      identification are explained for soybean proteomics. All this information would
      not only enrich us in understanding the plants response to environmental
      stressors but would also enable us to design genetically engineered stress
      tolerant soybean. 

PMID- 24136533
TI  - Proteome analysis of orphan plant species, fact or fiction?
AB  - Biological research has focused in the past on model organisms and most of the
      functional genomics studies in the field of plant sciences are still performed on
      model species or reference species that are characterized to a great extent.
      However, numerous non-model plants are essential as food, feed, or energy
      resource. Some features and processes are unique to these plant species or
      families and cannot be approached via a model plant. The power of all proteomic
      and transcriptomic methods, i.e., high throughput identification of candidate
      gene products, tends to be lost in orphan species due to the lack of genomic
      information, the complexity of the genome (protein inference problem, polyploidy)
      or due to the sequence divergence to a related sequenced reference variety or to
      a related model organism. Nevertheless, a proteomics approach has a great
      potential to study orphan species. This chapter reviews concisely orphan plants
      from a proteomic angle and provides an outline of the problems encountered when
      initiating the proteome analysis of a non-model organism. We discuss briefly the
      problems and solutions for orphan plants associated with sample preparation and
      focus further on the difficulties associated with protein redundancy in polyploid
      species and the protein inference issue which is particularly associated with a
      peptide based proteomics approach. 

PMID- 24136534
TI  - An improved detergent-compatible gel-fractionation LC-LTQ-Orbitrap-MS workflow
      for plant and microbial proteomics.
AB  - In proteomics, liquid chromatography coupled to mass spectrometry (LC-MS/MS) is
      an invaluable technique to accurately identify and quantify large sets of
      proteins. In this chapter we show a time-effective, and detergent compatible, Ge
      LC-LTQ-Orbitrap/MS proteomics workflow. The compatibility of this protocol with
      high concentrations of detergents significantly increases the extraction yield
      and the abundance of membrane proteins while gel fractionation increases the
      number of protein identifications. In our hands this workflow allows the
      identification of more than 1,500 proteins per sample, harvesting less than 20 mg
      of fresh weight, in many different organisms such as Chlamydomonas, Cyanothece,
      Arabidopsis, or Nicotiana, various microbes and enriched microbial samples.

PMID- 24136535
TI  - Seed proteomics.
AB  - Rather than providing a single specific protocol, the inclusive area of seed
      proteomics is reviewed; methods are described and compared and primary literature
      citations are provided. The limitations and challenges of proteomics as an
      approach to study seed biology are emphasized. The proteomic analysis of seeds
      encounters some specific problems that do not impinge on analyses of other plant
      cells, tissues, or organs. There are anatomic considerations. Seeds comprise the
      seed coat, the storage organ(s), and the embryonic axis. Are these to be studied
      individually or as a composite? The physiological status of the seeds must be
      considered; developing, mature, or germinating? If mature, are they quiescent or
      dormant? If mature and quiescent, then orthodox or recalcitrant? The genetic
      uniformity of the population of seeds being compared must be considered. Finally,
      seeds are protein-rich and the extreme abundance of the storage proteins results
      in a study-subject with a dynamic range that spans several orders of magnitude.
      This represents a problem that must be dealt with if the study involves analysis
      of proteins that are of "normal" to low abundance. Several different methods of
      prefractionation are described and the results compared. 

PMID- 24136536
TI  - Back to Osborne. Sequential protein extraction and LC-MS analysis for the
      characterization of the Holm oak seed proteome.
AB  - It is impossible to capture in just one experiment all or most of the total set
      of protein species that constitute the cell's proteome. Thus, according to our
      results, and even considering that they depend on the experimental system carried
      out (plant, yeast, fungi, or bacteria), the best protein extraction protocol
      yielded less than 20 % of the total amount of proteins, as determined by the
      Kjeldahl method. For this reason, protein cataloguing and the whole proteome
      characterization require the use of firstly, fractionation techniques at the
      cellular, subcellular, protein, or peptide level, and secondly, the use of
      complementary approaches.Within our current research on Holm oak (Quercus ilex
      subsp. ballota), we aim to characterize its seed proteome. For that we have
      optimized an experimental workflow in which the Osborne sequential protein
      extraction (Osborne, Science 28:417-427, 1908) is combined with downstream
      electrophoretic protein separation or shotgun MS analysis. In general, it can be
      used to study any plant seed, as well as to investigate on seed maturation and
      germination, genotype characterization, allergens identification, food
      traceability, and substantial equivalence, among others.

PMID- 24136537
TI  - Xylem sap proteomics.
AB  - Proteomic analysis of xylem sap has recently become a major field of interest to
      understand several biological questions related to plant development and
      responses to environmental clues. The xylem sap appears as a dynamic fluid
      undergoing changes in its proteome upon abiotic and biotic stresses. Unlike cell
      compartments which are amenable to purification in sufficient amount prior to
      proteomic analysis, the xylem sap has to be collected in particular conditions to
      avoid contamination by intracellular proteins and to obtain enough material. A
      model plant like Arabidopsis thaliana is not suitable for such an analysis
      because efficient harvesting of xylem sap is difficult. The analysis of the xylem
      sap proteome also requires specific procedures to concentrate proteins and to
      focus on proteins predicted to be secreted. Indeed, xylem sap proteins appear to
      be synthesized and secreted in the root stele or to originate from dying
      differentiated xylem cells. This chapter describes protocols to collect xylem sap
      from Brassica species and to prepare total and N-glycoprotein extracts for
      identification of proteins by mass spectrometry analyses and bioinformatics.

PMID- 24136538
TI  - Suspension-cultured plant cells as a tool to analyze the extracellular proteome.
AB  - Suspension-cultured cells (SCC) are generally considered the most suitable cell
      systems to carry out scientific studies, including the extracellular proteome
      (secretome). SCC are initiated by transferring friable callus fragments into
      flasks containing liquid culture medium for cell biomass growth, and they are
      maintained in an orbital shaker to supply the sufficient oxygen that allows cell
      growth. SCC increase rapidly during the exponential phase and after 10-20 days
      (depending on the cell culture nature), the growth rate starts to decrease due to
      limitation of nutrients, and to maintain for decades these kinds of cell cultures
      is needed to transfer a portion of these SCC into a fresh culture medium. Despite
      the central role played by extracellular proteins in most processes that control
      growth and development, the secretome has been less well characterized than other
      subcellular compartments, meaning that our understanding of the cell wall
      physiology is still very limited. Useful proteomic tools have emerged in recent
      years to unravel metabolic network that occurs in cell walls. With the recent
      progress made in mass spectrometry technology, it has become feasible to identify
      proteins from a given organ, tissue, cells, or even a subcellular compartment.
      Compared with other methods used to isolate cell wall proteins, the spent medium
      of SCC provides a convenient, continuous, and reliable and unique source of
      extracellular proteins. Therefore, this biological system could be used as a
      large-scale cell culture from which these proteins can be secreted, easily
      separated from cells without cell disruption, and so, without any cytosolic
      contamination, easily recovered from the extracellular medium. This
      nondestructive cell wall proteome approach discloses a set of proteins that are
      specifically expressed in the remodelling of the cell wall architecture and
      stress defense. 

PMID- 24136539
TI  - Pollen cultivation and preparation for proteomic studies.
AB  - The quality of the collected experimental data very much depends on the quality
      of the biological starting material. Especially the proteome analysis of a highly
      dynamic system like the germinating and tube-growing pollen grain needs several
      precautions which allow an accurate and acceptable interpretation of the obtained
      results. Optimized protocols for pollen collection, storage, and in vitro culture
      as well as pollen organelle separations are described which help to obtain well
      defined and reproducible experimental conditions for the subsequent proteomic
      analysis. 

PMID- 24136540
TI  - Isolation of the plant cytosolic fraction for proteomic analysis.
AB  - The cytosol is the fluid portion of the cell that is not partitioned by
      membranes. It contains a highly diverse collection of substances and is central
      to many essential cellular processes ranging from signal transduction, metabolite
      production and transport, protein biosynthesis and degradation to stress response
      and defense. Despite its importance, only a few proteomic studies have been
      performed on the plant cytosol. This is largely due to difficulties in isolating
      relatively pure samples from plant material free of disrupted organelle material.
      In this chapter we outline methods for isolating the cytosolic fraction from
      Arabidopsis cell cultures and seedlings and provide guidance on assessing purity
      for analysis by mass spectrometry. 

PMID- 24136541
TI  - Quantitative proteomic analysis of intact plastids.
AB  - Plastids are specialized cell organelles in plant cells that are differentiated
      into various forms including chloroplasts, chromoplasts, and amyloplasts, and
      fulfill important functions in maintaining the overall cell metabolism and
      sensing environmental factors such as sunlight. It is therefore important to
      grasp the mechanisms of differentiation and functional changes of plastids in
      order to enhance the understanding of vegetality. In this chapter, details of a
      method for the extraction of intact plastids that makes analysis possible while
      maintaining the plastid functions are provided; in addition, a quantitative
      shotgun method for analyzing the composition and changes in the content of
      proteins in plastids as a result of environmental impacts is described.

PMID- 24136542
TI  - Shotgun proteomics of plant plasma membrane and microdomain proteins using nano
      LC-MS/MS.
AB  - Shotgun proteomics allows the comprehensive analysis of proteins extracted from
      plant cells, subcellular organelles, and membranes. Previously, two-dimensional
      gel electrophoresis-based proteomics was used for mass spectrometric analysis of
      plasma membrane proteins. In order to get comprehensive proteome profiles of the
      plasma membrane including highly hydrophobic proteins with a number of
      transmembrane domains, a mass spectrometry-based shotgun proteomics method using
      nano-LC-MS/MS for proteins from the plasma membrane proteins and plasma membrane
      microdomain fraction is described. The results obtained are easily applicable to
      label-free protein semiquantification. 

PMID- 24136543
TI  - Plant mitochondrial proteomics.
AB  - Mitochondria are responsible for a number of major biochemical processes in plant
      cells including oxidative phosphorylation and photorespiration. Traditionally
      their primary role has been viewed as the oxidation of organic acids via the
      tricarboxylic acid cycle and the synthesis of ATP coupled to the transfer of
      electrons to O2. More recently its role in the synthesis of many metabolites such
      as amino acids, lipids, and vitamins has been revealed. They also contain large
      number of transporters including members of the mitochondrial carrier substrate
      family (MCSF) that allow the exchange of metabolites with the cytosol.
      Mitochondria also contain their own genome and actively transcribe and translate
      a set of proteins that are coordinated with proteins encoded by the nuclear
      genome to produce large multisubunit enzymes. To reveal the full diversity of
      metabolism carried out by mitochondria significant efforts have sought to uncover
      the protein profile of mitochondria from both crops and model plants. Successful
      proteomic analysis depends on the preparation of high-quality isolated
      mitochondria, coupled to high-resolution proteomic techniques for identification,
      quantitation, and assessment of the degree of contamination by other organelles
      and cellular compartments. Here we outline a mitochondrial isolation protocol
      that can be applied to a range of plant tissues, and detail methods of assessing
      the quality and purity of the resultant sample, including calculations of
      respiratory control ratio, marker enzyme assays, differential in-gel
      electrophoresis, and quantitative gel-free mass spectrometry. 

PMID- 24136544
TI  - Separation of the plant Golgi apparatus and endoplasmic reticulum by free-flow
      electrophoresis.
AB  - Free-flow electrophoresis (FFE) is a technique for separation of proteins,
      peptides, organelles, and cells. With zone electrophoresis (ZE-FFE), organelles
      are separated according to surface charge. The plant Golgi and endoplasmic
      reticulum (ER) are similar in density and are therefore separated with difficulty
      using standard techniques such as density centrifugation. Purification of the ER
      and Golgi apparatus permits a biochemical and proteomic characterization which
      can reveal the division of processes between these compartments. Here we describe
      complete separation between the ER and more negatively charged Golgi compartments
      using ZE-FFE. We also describe techniques for assigning proteins to partially
      separated ER and the less negatively charged Golgi compartments.

PMID- 24136545
TI  - Isolation of leaf peroxisomes from Arabidopsis for organelle proteome analyses.
AB  - The isolation of cell organelles from model organisms in high purity is important
      for biochemical analyses of single proteins, entire metabolic pathways, and
      protein complexes and is absolutely essential for organelle proteome analyses.
      The efficient enrichment of nearly all cell organelles is more difficult from
      Arabidopsis as compared to traditional model plants and especially challenging
      for peroxisomes. Leaf peroxisomes are generally very instable in aqueous solution
      due to the presence of a single membrane and (para-)crystalline inclusions in the
      matrix. Leaf peroxisomes from Arabidopsis are particularly fragile and, moreover,
      strongly physically adhere to chloroplasts and mitochondria for largely unknown
      reasons. Here, we provide a detailed protocol for the isolation of Arabidopsis
      leaf peroxisomes by Percoll followed by sucrose density gradient centrifugation
      that yields high purity suitable for proteome analyses. Diverse enzymatic and
      immuno-biochemical methods are summarized to assess purity and intactness. 

PMID- 24136546
TI  - Proteomics of field samples in radioactive Chernobyl area.
AB  - Two serious nuclear accidents during the past quarter of a century contaminated
      large agricultural areas with radioactivity. The remediation and possible
      recovery of radio-contaminated areas for agricultural purposes require
      comprehensive characterization of plants grown in such places. Here we describe
      the quantitative proteomics method that we use to analyze proteins isolated from
      seeds of plants grown in radioactive Chernobyl zone. 

PMID- 24136547
TI  - Differential proteome and secretome analysis during rice-pathogen interaction.
AB  - Substantial evidences implicate that sample preparation and protein extraction in
      proteomic studies of plant-pathogen interactions are critical to understand cross
      talk between host and pathogen. Therefore, interest is growing in applying
      proteomics techniques to investigate simultaneously secreted proteins from rice
      and pathogen. We have found, however, that most proteins of interest are low
      abundant so that proper prefractionation or extraction of secreted proteins from
      extracellular space (ECS) in the rice leaf is required to excavate relevant
      protein. This chapter describes the preparation of sample and extraction
      procedure to enrich the proteins interested before separation by 2-DE or LC
      MS/MS. This method significantly increases the sensitivity of proteomic
      comparisons.

PMID- 24136548
TI  - Protein extraction and gel-based separation methods to analyze responses to
      pathogens in carnation (Dianthus caryophyllus L).
AB  - We are currently using a 2-DE-based proteomics approach to study plant responses
      to pathogenic fungi by using the carnation (Dianthus caryophyllus L)-Fusarium
      oxysporum f. sp. dianthi pathosystem. It is clear that the protocols for the
      first stages of a standard proteomics workflow must be optimized to each
      biological system and objectives of the research. The optimization procedure for
      the extraction and separation of proteins by 1-DE and 2-DE in the indicated
      system is reported. This strategy can be extrapolated to other plant-pathogen
      interaction systems in order to perform an evaluation of the changes in the host
      protein profile caused by the pathogen and to identify proteins which, at early
      stages, are involved or implicated in the plant defense response.

PMID- 24136549
TI  - StageTip-based HAMMOC, an efficient and inexpensive phosphopeptide enrichment
      method for plant shotgun phosphoproteomics.
AB  - Phosphopeptide enrichment is the most critical step for successful LC-MS/MS-based
      shotgun phosphoproteomics. Recent technological improvements have made selective
      phosphopeptide enrichment from non-fractionated whole cell lysate digests with a
      single-step procedure possible. Here, a handy protocol is described for
      phosphopeptide enrichment from plant materials using hydroxy acid-modified metal
      oxide chromatography (HAMMMOC) with a stop-and-go-extraction tip (StageTip).

PMID- 24136550
TI  - Simultaneous identification and quantification of nitrosylation sites by
      combination of biotin switch and ICAT labeling.
AB  - S-nitrosylation is a widespread modification of proteins. In plants, most
      information available to date regarding this modification was obtained using
      nitric oxide donors and concerned the proteins but not the identification of
      cysteine residues specifically modified in the proteins or their quantification.
      Here, we describe a method for the identification of endogenously nitrosylated
      cysteines in Arabidopsis and, simultaneously, the measurement of relative change
      in their abundance within binary comparisons. 

PMID- 24136551
TI  - Tandem metal-oxide affinity chromatography for enhanced depth of phosphoproteome
      analysis.
AB  - In eukaryotic cells many diverse cellular functions are regulated by reversible
      protein phosphorylation. In recent years, phosphoproteomics has become a powerful
      tool to study protein phosphorylation because it allows unbiased localization,
      and site-specific quantification, of in vivo phosphorylation of hundreds of
      proteins in a single experiment. A common strategy to identify phosphoproteins
      and their phosphorylation sites from complex biological samples is the enrichment
      of phosphopeptides from digested cellular lysates followed by mass spectrometry.
      However, despite the high sensitivity of modern mass spectrometers the large
      dynamic range of protein abundance and the transient nature of protein
      phosphorylation remained major pitfalls in MS-based phosphoproteomics. Tandem
      metal-oxide affinity chromatography (MOAC) represents a robust and highly
      selective approach for the identification and site-specific quantification of low
      abundant phosphoproteins that is based on the successive enrichment of
      phosphoproteins and -peptides. This strategy combines protein extraction under
      denaturing conditions, phosphoprotein enrichment using Al(OH)3-based MOAC,
      tryptic digestion of enriched phosphoproteins followed by TiO2-based MOAC of
      phosphopeptides. Thus, tandem MOAC effectively targets the phosphate moiety of
      phosphoproteins and phosphopeptides and, thus, allows probing of the
      phosphoproteome to unprecedented depth.

PMID- 24136552
TI  - N-glycoprotein enrichment by lectin affinity chromatography.
AB  - Lectins are proteins that bind to sugars with varying specificities and several
      have been identified that show differential binding to structurally variable
      glycans attached to glycoproteins. Consequently, lectin affinity chromatography
      represents a valuable tool for glycoproteome studies, allowing enrichment of
      glycoproteins in samples prior to their identification by mass spectrometry (MS).
      From the perspective of plant scientists, lectin enrichment has proven useful for
      studies of the proteomes of the secretory pathways and cell wall, due to the high
      proportion of constituent proteins that are glycosylated. This chapter outlines a
      strategy to generate samples enriched with glycoproteins from bulk plant tissues
      prior to further characterization by MS, or other techniques.

PMID- 24136553
TI  - Rapid and high-throughput N-glycomic analysis of plant glycoproteins.
AB  - Glycoprotein is a major element in higher organisms including mammalians and
      plants. It is widely accepted that variation in cellular N-glycome is related to
      modulation in dynamic cellular mechanisms such as cell-cell adhesion, cell
      activation, and malignant alterations in mammalian cells. However, the
      physiological importance of glycan modification of glycoproteins in plant cells
      is still a matter of dispute. Therefore, a comprehensive and high-throughput
      analysis of N-glycome in plant glycoproteins is needed. Here, an application of
      the glycoblotting-mass spectrometry technique to plant glycoprotein research is
      described.

PMID- 24136554
TI  - Assay for proteasome-dependent protein degradation and ubiquitinated proteins.
AB  - The ubiquitin-26S proteasome system (UPS) plays a crucial role in selective
      removal of short-lived target proteins, archiving fine-tuning of post-translation
      levels of the target proteins. Recently a number of ubiquitin ligases (E3) have
      been reported as essential regulators of various plant developmental cues and
      stress responses. To clarify the detailed biochemical and physiological function
      of the E3 proteins, identification of their target proteins is of great
      importance. A transient expression system with tobacco leaves is a powerful
      method to evaluate E3 function and target degradation via UPS. Here simple
      methods to assay proteasome-dependent protein degradation combined with a tobacco
      transient expression system and detection of accumulation of ubiquitinated
      proteins are presented. 

PMID- 24136555
TI  - Separation of membrane protein complexes by native LDS-PAGE.
AB  - Gel electrophoresis has become one of the most important methods for the analysis
      of proteins and protein complexes in a molecular weight range of 1-10(7) kDa. The
      separation of membrane protein complexes remained challenging to standardize
      until the demonstration of Blue Native PAGE in 1991 [1] and Clear Native PAGE in
      1994 [2]. We present a robust protocol for high-resolution separation of
      photosynthetic complexes from Arabidopsis thaliana using lithium dodecyl sulfate
      as anion in a modified Blue Native PAGE (LDS-PAGE). Here, non-covalently bound
      chlorophyll is used as a sensitive probe to characterize the assembly/biogenesis
      of the pigment-protein complexes essential for photosynthesis. The high
      fluorescence yield recorded from chlorophyll-binding protein complexes can also
      be used to establish the separation of native protein complexes as an
      electrophoretic standard. 

PMID- 24136556
TI  - Identification of thioredoxin target disulfides using isotope-coded affinity
      tags.
AB  - Thioredoxins (Trx) are small redox proteins that reduce disulfide bonds in
      various target proteins and maintain cellular thiol redox control. Here, a thiol
      specific labeling and affinity enrichment approach for identification and
      relative quantification of Trx target disulfides in complex protein extracts is
      described. The procedure utilizes the isotope-coded affinity tag (ICAT) reagents
      containing a thiol reactive iodoacetamide group and a biotin affinity tag to
      target peptides containing reduced cysteine residues. The identification of
      substrates for Trx and the extent of target disulfide reduction is determined by
      LC-MS/MS-based quantification of tryptic peptides labeled with "light" ((12)C)
      and "heavy" ((13)C) ICAT reagents. The methodology can be adapted to monitor the
      effect of different reductants or oxidants on the redox status of thiol/disulfide
      proteomes in biological systems.

PMID- 24136557
TI  - Class III peroxidases.
AB  - Class III peroxidases are heme-containing proteins of the secretory pathway with
      an extremely high number of isoenzymes, indicating the tremendous and important
      functions of this protein family. This chapter describes fractionation of the
      cell in subproteomes, their separation by polyacrylamide gel electrophoresis
      (PAGE) and visualization of peroxidase isoenzymes by heme and specific in-gel
      staining procedures. Soluble and membrane-bound peroxidases were separated by
      differential centrifugation. Aqueous polymer two-phase partitioning and
      discontinuous sucrose density gradient were applied to resolve peroxidase
      profiles of plasma membranes and tonoplast. Peroxidase isoenzymes of subproteomes
      were further separated by PAGE techniques such as native isoelectric focussing
      (IEF), high resolution clear native electrophoresis (hrCNE), and modified sodium
      dodecyl sulfate (modSDS)-PAGE. These techniques were used as stand-alone method
      or in combination for two-dimensional PAGE.

PMID- 24136558
TI  - Proteotyping of Holm oak (Quercus ilex subsp. ballota) provenances through
      proteomic analysis of acorn flour.
AB  - Proteomics has become a powerful tool to characterize biodiversity and natural
      variability in plant species, as well as to catalogue and establish phylogenetic
      relationships and distances among populations, provenances or ecotypes. In this
      chapter, we describe the standard proteomics workflow that we currently use in
      cataloguing Holm oak (Quercus ilex subsp. ballota [Desf.] Samp.) populations.
      Proteins are extracted from acorn flour or pollen by TCA/acetone or TCA/acetone
      phenol methods, resolved by one- or two-dimensional gel electrophoresis, and gel
      images are captured and analyzed by appropriate software and statistical
      packages. Quantitative or qualitative variable bands or spots are subjected to MS
      analysis in order to identify them and correlate differences in the protein
      profile with the phenotypes or environmental conditions.

PMID- 24136559
TI  - Immunoproteomics analysis of food allergens.
AB  - Immunoblot-coupled proteomics based on two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE), namely, immunoproteomics, has been used for
      comprehensive identification of food allergens, because it is a simple and
      inexpensive tool for rapid identification of several IgE-binding proteins. In
      this section, we describe our protocols for identification of food allergens
      using immunoproteomics and discuss a few technical points in detail.

PMID- 24136560
TI  - Beer and wort proteomics.
AB  - Proteome analysis provides a way to identify proteins related to the quality
      traits of beer. A number of protein species in beer and wort have been identified
      by two-dimensional gel electrophoresis combined with enzyme digestion such as
      trypsin, followed by mass spectrometry analyses and/or liquid chromatography
      mass/mass spectrometry. In addition, low molecular weight polypeptides in beer
      have been identified by the combination of non-enzyme digestion and mass
      analyses. These data sets of various molecular weight polypeptides (i.e.,
      proteomes) provide a platform for analyzing protein functions in beer. Several
      novel proteins related to beer quality traits such as foam stability and haze
      formation have been identified by analyzing these proteomes. Some of the proteins
      have been applied to the development of efficient protein or DNA markers for
      trait selection in malting barley breeding. In this chapter, recent proteome
      studies of beer and wort are reviewed, and the methods and protocols of beer and
      wort proteome analysis are described. 

PMID- 24136561
TI  - Precipitation of champagne base wine proteins prior to 2D electrophoresis.
AB  - Numerous methods have been employed to depict the protein content of wines. Among
      them, two-dimensional electrophoresis (2D-E) presents a powerful resolution, but
      has been poorly applied to wine. Furthermore, 2D-E was coupled with various
      extraction methods of proteins without any reference method for wine. Here, we
      describe a rapid method to extract proteins from a champagne base wine through
      ultrafiltration followed by precipitation with ethanol and trichloroacetic acid.
      More than 50 spots were visualized on 2D-gels (7 cm, pH 3-6) by colloidal
      Coomassie Brilliant Blue staining. 

PMID- 24136562
TI  - The Minimal Information about a Proteomics Experiment (MIAPE) from the Proteomics
      Standards Initiative.
AB  - During the last 10 years, the Proteomics Standards Initiative from the Human
      Proteome Organization (HUPO-PSI) has worked on defining standards for proteomics
      data representation as well as guidelines that state the minimum information that
      should be included when reporting a proteomics experiment (MIAPE). Such minimum
      information must describe the complete experiment, including both experimental
      protocols and data processing methods, allowing a critical evaluation of the
      whole process and the potential recreation of the work. In this chapter we
      describe the standardization work performed by the HUPO-PSI, and then we
      concentrate on the MIAPE guidelines, highlighting its importance when publishing
      proteomics experiments particularly in specialized proteomics journals. Finally,
      we describe existing bioinformatics resources that generate MIAPE compliant
      reports or that check proteomics data files for MIAPE compliance.

PMID- 24136563
TI  - Repetitive stepwise rotaxane formation toward programmable molecular arrays.
AB  - We present a novel strategy to synthesize multi-molecular arrays in a
      programmable way by stepwise elongation based on repetition of two-fold rotaxane
      formation and construction of threads. A cofacially triply stacked porphyrin
      array was obtained via the repetitive two-fold rotaxane formation. 

PMID- 24136564
TI  - Embryonic development of Zoraptera with special reference to external morphology,
      and its phylogenetic implications (Insecta).
AB  - The embryonic development of Zorotypus caudelli Karny (Zoraptera) is described
      with the main focus on its external features. A small heart-shaped embryo is
      formed on the dorsal side of the egg by the fusion of paired blastoderm regions
      with higher cellular density. The orientation of its anteroposterior axis is
      opposed to that of the egg. This unusual condition shows the potential
      autapomorphy of Zoraptera. The embryo extends along the egg surface and after
      reaching its full length, it migrates into the yolk. After developing there for a
      period of time, it reappears on the surface, accompanied by a reversion of its
      anteroposterior axis, finally taking its position on the ventral side of the egg.
      The definitive dorsal closure completes, and the prelarva hatches after
      perforating the chorion with very long egg tooth formed on the embryonic cuticle.
      Embryological data suggest the placement of Zoraptera among the "lower neopteran"
      or polyneopteran lineage: features supporting this are embryo formation by the
      fusion of paired regions with higher cellular density and blastokinesis
      accompanied by full elongation of the embryo on the egg surface. The
      extraordinarily long egg tooth has potential synapomorphy with Embioptera or
      Eukinolabia (= Embioptera + Phasmatodea). Together with the results from our
      previous studies on the egg structure, male reproductive system and spermatozoa,
      the close affinity of Zoraptera with Eukinolabia appears likely, that is, a clade
      Zoraptera + (Embioptera + Phasmatodea).

PMID- 24136565
TI  - Screening and characterization of protease producing actinomycetes from marine
      saltern.
AB  - In the course of systematic screening program for bioactive actinomycetes, an
      alkaline protease producing halophilic strain Actinopolyspora sp. VITSDK2 was
      isolated from marine saltern, Southern India. The strain was identified as
      Actinopolyspora based on its phenotypic and phylogenetic characters. The protease
      was partially purified using ammonium sulfate precipitation and subsequently by
      DEAE cellulose column chromatography. The enzyme was further purified using HPLC
      and the molecular weight was found to be 22 kDa as determined by SDS-PAGE
      analysis. The purified protease exhibited pH stability in a wide range of 4-12
      with optimum at 10.0. The enzyme was found to be stable between 25 and 80 
      degrees C and displayed a maximum activity at 60  degrees C. The enzyme activity
      was increased marginally in presence of Mn(2+) , Mg(2+) , and Ca(2+) and
      decreased in presence of Cu(2+) . PMSF and DFP completely inhibited the activity
      suggesting it belongs to serine protease. Further, the proteolytic activity was
      abolished in presence of N-tosyl-L-lysine chloromethyl ketone suggesting this
      might be chymotrypsin-like serine protease. The protease was 96% active when kept
      for 10 days at room temperature. The results indicate that the enzyme belong to
      chymotrypsin-like serine protease exhibiting both pH and thermostability, which
      can be used for various applications in industries.

PMID- 24136566
TI  - A review of treatment of uterine leiomyosarcomas.
AB  - Uterine leiomyosarcomas are rare but challenging tumours. They occur most
      commonly around or shortly after the menopause. Their clinical behaviour is very
      variable, from highly aggressive to very indolent. Most are diagnosed
      unexpectedly and thus initially operated on by general gynaecologists. This
      article discusses the important surgical issues and the role of adjuvant
      treatments such as radiotherapy and chemotherapy. Important new international
      trials are opening to address these issues. Relapsed disease is usually
      incurable, but a subgroup of patients may benefit from repeated surgical
      procedures, hormones and ablative therapies. The choice of drugs for chemotherapy
      is discussed. New approaches with targeted agents have yet to establish
      themselves in treatment of leiomyosarcomas. 

PMID- 24136567
TI  - Reply to Bhavsar et al.

PMID- 24136568
TI  - Factors affecting outcomes of corneal collagen crosslinking treatment.
AB  - PURPOSE: To assess the effects of preoperative patient characteristics on
      clinical outcomes of corneal crosslinking (CXL) treatment in patients with
      progressive keratoconus. METHODS: This retrospective study comprised 96 eyes of
      96 patients who had unilateral CXL treatment for progressive keratoconus. All
      patients underwent a complete ophthalmological examination and corneal topography
      at baseline and 1 year. Subgroup analyses were performed according to the age
      (<30 and >= 30 years), gender, preoperative corrected distance visual acuity
      (CDVA, <0.3 and >= 0.3 logMAR (log of the minimum angle of resolution)),
      preoperative maximum keratometry (K, <54 and >= 54 D), baseline topographic cone
      location (central, paracentral, and peripheral), and preoperative thinnest
      pachymetry (<450 and >= 450 MUm) to determine the associations between
      preoperative patient characteristics and outcomes (changes in visual acuity and
      maximum keratometry) of CXL treatment. RESULTS: In the entire study population,
      mean CDVA and maximum K significantly improved after CXL treatment (P<0.001).
      Patients with a preoperative CDVA of 20/40 Snellen equivalent or worse (>= 0.3
      logMAR) experienced more visual improvement after CXL treatment (P<0.001).
      However, an age >= 30 years and a baseline thinnest pachymetry less than 450 MUm
      were found significantly associated with more flattening in maximum keratometry
      (P=0.024, P=0.005 respectively). Gender, preoperative maximum K, and baseline
      topographic cone location did not show significant effect on postoperative visual
      acuity and maximum keratometry (P>0.05). CONCLUSIONS: In patients with
      progressive keratoconus, age, baseline visual acuity, and baseline thinnest
      pachymetry seem to affect the success of the CXL treatment.

PMID- 24136569
TI  - National survey of progressive symptomatic retinal detachment complicating
      retinoschisis in the United Kingdom.

PMID- 24136570
TI  - Reply to Wakefield and Kumar.

PMID- 24136571
TI  - Corneal changes after a single session of selective laser trabeculoplasty for
      open-angle glaucoma.
AB  - PURPOSE: To investigate the changes in endothelial cell count, central corneal
      thickness (CCT), and refractive error after a session of selective laser
      trabeculoplasty (SLT) for open angle glaucoma (OAG). METHODS: This prospective
      cohort study recruited 111 eyes of 66 consecutive subjects with OAG. Subjects
      received SLT to 360 degrees  of the trabecular meshwork. Endothelial cell count,
      CCT, and spherical equivalent were measured at baseline before SLT as well as at
      1 week and 1 month post SLT. A repeated measure nested ANOVA with Tukey's
      multiple comparison test was performed to compare the outcome measures before and
      after SLT. RESULTS: In 111 eyes of 66 subjects, the mean number of laser
      applications per treatment was 166.9 +/- 41.4 with a mean energy level of 1.0 +/-
      0.07 mJ. The mean endothelial cell count decreased significantly from 2465.0 +/-
      334.0 cells/mm(2) at baseline to 2355.0 +/- 387.0 cells/mm(2) at 1 week
      (P=0.0004) but increased to baseline levels at 1 month post SLT (2424.0 +/- 379.4
      cells/mm(2), P=0.3). The CCT, which decreased from a baseline of 549.4 +/- 37.6
      to 543.9 +/- 40.2 MUm at 1 week post SLT (P=0.02), also returned to the baseline
      level by 1 month (P=0.2). The spherical equivalent was static from baseline. A
      positive correlation was found between total laser energy and CCT at 1 month post
      treatment (r=0.3, P=0.005). CONCLUSION: The transient reductions in endothelial
      cell count and CCT following SLT returned to baseline levels 1 month after the
      procedure. Patients undergoing SLT should be aware of the risk of potential
      corneal changes.

PMID- 24136572
TI  - Liver failure following antituberculosis (ATT) chemotherapy for presumed
      tuberculous uveitis.

PMID- 24136573
TI  - Comment on: Pathogenic conjunctival bacteria associated with systemic co
      morbidities of patients undergoing cataract surgery.

PMID- 24136574
TI  - Intravitreal injections, antibiotics and endophthalmitis.

PMID- 24136575
TI  - Response to Nestel.

PMID- 24136576
TI  - Xenobiotic benzotriazoles--biodegradation under meso- and oligotrophic conditions
      as well as denitrifying, sulfate-reducing, and anaerobic conditions.
AB  - The intensive use of benzotriazoles as corrosion inhibitors for various
      applications and their application in dishwasher detergents result in an almost
      omnipresence of benzotriazole (BTri), 4-methyl- and 5-methyl-benzotriazole (4
      TTri and 5-TTri, respectively) in aquatic systems. This study aims on the
      evaluation of the biodegradation potential of activated sludge communities (ASCs)
      toward the three benzotriazoles regarding aerobic, anoxic, and anaerobic
      conditions and different nutrients. ASCs were taken from three wastewater
      treatment plants with different technologies, namely, a membrane bioreactor (MBR
      MH), a conventional activated sludge plant CAS-E (intermittent
      nitrification/denitrification), and CAS-M (two-stage activated sludge treatment)
      and used for inoculation of biodegradation setups. All ASCs eliminated up to 30
      mg L(-1) 5-TTri and BTri under aerobic conditions within 2-7 and 21-49 days,
      respectively, but not under anoxic or anaerobic conditions. 4-TTri was refractory
      at all conditions tested. Significant differences were observed for BTri
      biodegradation with non-acclimated ASCs from MBR-MH with 21 days, CAS-E with 41
      days, and CAS-M with 49 days. Acclimated ASCs removed BTri within 7 days.
      Furthermore, different carbon and nitrogen concentrations revealed that nitrogen
      was implicitly required for biodegradation while carbon showed no such effect.
      The fastest biodegradation occurred for 5-TTri with no need for acclimatization,
      followed by BTri. BTri showed sludge-specific biodegradation patterns, but, after
      sludge acclimation, was removed with the same pattern, regardless of the sludge
      used. Under anaerobic conditions in the presence of different electron acceptors,
      none of the three compounds showed biological removal. Thus, presumably, aerobic
      biodegradation is the major removal mechanism in aquatic systems. 

PMID- 24136577
TI  - Contribution of vehicular traffic and industrial facilities to PM10
      concentrations in a suburban area of Caserta (Italy).
AB  - PM10 levels have been recorded in the suburban area of Caserta (Italy) from
      February to October 2012. The daily limit was exceeded in 13 % of the
      determinations, with no significant difference between weekdays and weekends.
      Benzo[a]pyrene concentrations were in the range 0.01-0.46 ng/m(3), thus, never
      exceeding the National Standard. The B(a)P-eq was 0.20 ng/m(3). PM10 peaks were
      associated with wind from east-northeast. The same was observed for Ca
      concentrations, whereas no relation with wind direction was observed for organic
      pollutants. The results point to a local limestone quarry and cement factory as
      the likely major source of PM10 pollution in the area investigated.

PMID- 24136578
TI  - A new bioseed for determination of wastewater biodegradability: analysis of the
      experimental procedure.
AB  - A new bioassay proposed in the patent P201300029 was applied to a pre-treated
      wastewater containing a mixture of commercial pesticides to simulate a
      recalcitrant industrial wastewater in order to determine its biodegradability.
      The test uses a mixture of standardized inoculum of the lyophilized bacteria
      Pseudomonas putida with the proper proportion of salts and minerals. The results
      highlight that biodegradation efficiency can be calculated using a gross
      parameter (chemical oxygen demand (COD)) which facilitates the biodegradability
      determination for routine water biodegradability analysis. The same trend was
      observed throughout the assay with the dehydrated and fresh inoculums, and only a
      difference of 5% in biodegradation efficiency (E f) was observed. The obtained
      results showed that the P. putida biodegradability assay can be used as a
      commercial test with a lyophilized inoculum in order to monitor the ready
      biodegradability of an organic pollutant or a WWTP influent. Moreover, a
      combination of the BOD5/COD ratio and the P. putida biodegradability test is an
      attractive alternative in order to evaluate the biodegradability enhancement in
      water pre-treated with advanced oxidation processes (AOPs).

PMID- 24136579
TI  - Frozen section pathology for decision making in parotid surgery.
AB  - IMPORTANCE: For parotid lesions, the high accuracy and utility of intraoperative
      frozen section (FS) pathology, compared with permanent section pathology,
      facilitates intraoperative decision making about the extent of surgery required.
      OBJECTIVE: To demonstrate the accuracy and utility of FS pathology of parotid
      lesions as one factor in intraoperative decision making. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective review of patients undergoing parotidectomy at a
      tertiary care center. INTERVENTIONS: Evaluation of the accuracy of FS pathology
      for parotid surgery by comparing FS pathology results with those of permanent
      section. MAIN OUTCOMES AND MEASURES: Documented changes from FS to permanent
      section in 1339 parotidectomy pathology reports conducted from January 1, 2000,
      through December 31, 2009, included 693 benign and 268 primary and metastatic
      malignant tumors. RESULTS: Changes in diagnosis were found from benign to
      malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity
      of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were
      for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of
      or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case
      changed from low- to high-grade malignant tumor. Only 4 cases that changed from
      FS to permanent section would have affected intraoperative decision making. Three
      patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient
      was overtreated (lymphoma initially deemed carcinoma). CONCLUSIONS AND RELEVANCE:
      Frozen section pathology for parotid lesions has high accuracy and utility in
      intraoperative decision making, facilitating timely complete procedures.

PMID- 24136580
TI  - Gestational exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin
      induces BRCA-1 promoter hypermethylation and reduces BRCA-1 expression in mammary
      tissue of rat offspring: preventive effects of resveratrol.
AB  - Studies with murine models suggest that maternal exposure to aromatic hydrocarbon
      receptor (AhR) agonists may impair mammary gland differentiation and increase the
      susceptibility to mammary carcinogenesis in offspring. However, the molecular
      mechanisms responsible for these perturbations remain largely unknown.
      Previously, we reported that the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) induced CpG methylation of the breast cancer-1 (BRCA-1) gene and reduced
      BRCA-1 expression in breast cancer cell lines. Based on the information both the
      human and rat BRCA-1 genes harbor xenobiotic responsive elements (XRE = 5'-GCGTG
      3'), which are binding targets for the AhR, we extended our studies to the
      analysis of offspring of pregnant Sprague-Dawley rats treated during gestation
      with TCDD alone or in combination with the dietary AhR antagonist resveratrol
      (Res). We report that the in utero exposure to TCDD increased the number of
      terminal end buds (TEB) and reduced BRCA-1 expression in mammary tissue of
      offspring. The treatment with TCDD induced occupancy of the BRCA-1 promoter by
      DNA methyltransferase-1 (DNMT-1), CpG methylation of the BRCA-1 promoter, and
      expression of cyclin D1 and cyclin-dependent kinase-4 (CDK4). These changes were
      partially overridden by pre-exposure to Res, which stimulated the expression of
      the AhR repressor (AhRR) and its recruitment to the BRCA-1 gene. These findings
      point to maternal exposure to AhR agonists as a risk factor for breast cancer in
      offspring through epigenetic inhibition of BRCA-1 expression, whereas dietary
      antagonists of the AhR may exert protective effects.

PMID- 24136581
TI  - Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine
      relevance to the treatment of neurological diseases.
AB  - At high concentrations, the glutamine synthetase inhibitor L-methionine-S,R
      sulfoximine (MSO) is a convulsant, especially in dogs. Nevertheless, sub
      convulsive doses of MSO are neuroprotective in rodent models of hyperammonemia,
      acute liver disease, and amyotrophic lateral sclerosis and suggest MSO may be
      clinically useful. Previous work has also shown that much lower doses of MSO are
      required to produce convulsions in dogs than in primates. Evidence from the mid
      20th century suggests that humans are also less sensitive. In the present work,
      the inhibition of recombinant human glutamine synthetase by MSO is shown to be
      biphasic-an initial reversible competitive inhibition (K i 1.19 mM) is followed
      by rapid irreversible inactivation. This K i value for the human enzyme accounts,
      in part, for relative insensitivity of primates to MSO and suggests that this
      inhibitor could be used to safely inhibit glutamine synthetase activity in
      humans. 

PMID- 24136583
TI  - Central nervous system angiitis in Hodgkin's disease.

PMID- 24136582
TI  - Multiple sites on Streptococcus gordonii surface protein PadA bind to platelet
      GPIIbIIIa.
AB  - Infective endocarditis is a life threatening disease caused by a bacterial
      infection of the endocardial surfaces of the heart. The oral pathogen,
      Streptococcus gordonii is amongst the most common pathogens isolated from
      infective endocarditis patients. Previously we identified a novel cell wall
      protein expressed on S. gordonii called platelet adherence protein A (PadA) that
      specifically interacts with platelet GPIIb/IIIa. The interaction between PadA and
      GPIIb/IIIa resulted in firm platelet adhesion, dense granule secretion and
      platelet spreading on immobilised S. gordonii. This study set out to identify
      specific motifs on the PadA protein that interacts with platelet GPIIb/IIIa.
      Proteomic analysis of the PadA protein identified two short amino acid motifs
      which have been previously shown to be important for fibrinogen binding to
      GPIIb/IIIa and contributing to the generation of outside-in signalling. Site
      directed mutagenesis on the PadA protein in which 454AGD was substituted to AAA,
      and the 383RGT was substituted to AAA suggests the RGT motif has no role in
      supporting platelet adhesion however plays a role in dense granule secretion and
      platelet spreading. In contrast to this the AGD motif has no role to play in
      supporting firm platelet adhesion or dense granule secretion however plays a role
      in platelet spreading. These results suggest that multiple sites on S. gordonii
      PadA interact with GPIIb/IIIa to mediate a number of platelet responses that
      likely contribute to the thrombotic complications of infective endocarditis.

PMID- 24136584
TI  - Is reduced myocardial sympathetic innervation associated with clinical symptoms
      of autonomic impairment in idiopathic Parkinson's disease?
AB  - Patients with idiopathic Parkinson's disease (IPD) have a reduced myocardial MIBG
      uptake in MIBG scintigraphy, indicating myocardial sympathetic denervation. We
      were interested whether this myocardial sympathetic denervation coincides with
      clinical symptoms of autonomic impairment in IPD patients. We performed MIBG
      scintigraphy, the SCOPA-AUT scale, a standardized medical history (developed in
      our clinic) and autonomic nervous system testing in 47 IPD patients (21 female,
      26 male patients). We correlated myocardial MIBG uptake with the results of the
      SCOPA-AUT scale, the standardized medical history and the autonomic nervous
      system testing through the use of Spearman's correlation. Myocardial MIBG uptake
      correlated significantly (p < 0.05) with several items of the SCOPA-AUT scale (in
      female patients: perspiration during the night, in male patients: sum score,
      saliva dribbling of the mouth, difficulty swallowing, fainting, constipation), of
      the standardized medical history (in male patients: swollen ankles) and of the
      autonomic nervous system testing (all patients: sum score, Ewing orthostasis
      test). Remarkably, we found more significant correlations in male than in female
      patients. Reduced myocardial sympathetic innervation-as revealed by MIBG
      scintigraphy-is associated with clinical symptoms of autonomic impairment. This
      association is more pronounced in male than in female patients. The cause for
      this gender-specific phenomenon is unclear.

PMID- 24136586
TI  - Patterns of FDG uptake in pancreatic non-Hodgkin's lymphoma lesions.
AB  - PURPOSE: The aim of this study was to evaluate the pattern of FDG uptake in
      pancreatic non-Hodgkin's lymphoma (NHL) lesions. METHODS: The study included 9
      consecutive patients with newly diagnosed NHL with pancreatic involvement who
      underwent an F-18 fluorodeoxyglucose positron emission tomography/computed
      tomography (F-18 FDG PET/CT) scan. The location, size, maximal standardized
      uptake value (SUVmax), and FDG uptake patterns of the pancreatic lesions were
      reviewed. RESULTS: Four different patterns of FDG uptake could be distinguished
      in the affected pancreas corresponding to different types of lymphoma lesions.
      These included focal FDG uptake by distinct solitary lesions (5 patients),
      multiple foci of FDG uptake corresponding to separate lymphoma lesions (1
      patient), segmental FDG uptake caused by lymphoma infiltration limited to a
      pancreatic segment (1 patient), and diffuse FDG uptake related to diffuse
      lymphomatous infiltration of the entire pancreas (2 patients). All types of
      lesions showed increased metabolic activity with maximal standardized uptake
      values (SUVmax) ranging from 7.4 to 26.5. On CT images, the segmental and diffuse
      patterns of FDG uptake correlated to segmental and diffuse pancreatic enlargement
      accordingly. All lesions showed isodensity or slight hypodensity in relation to
      pancreatic tissue. The pancreatic head was the most frequent site of involvement
      (8/9). Mildly dilated pancreatic duct was noted only in 2 patients. CONCLUSIONS:
      The described patterns of FDG uptake and correlative CT findings may be helpful
      for a better characterization of NHL involving the pancreas and for differential
      diagnosis with other lesions, including pancreatic adenocarcinomas.

PMID- 24136585
TI  - Dynamic changes and associated factors of clopidogrel resistance in patients
      after cerebral infarction.
AB  - Stroke victims often exhibit clopidogrel resistance (CR). This prospective study
      was undertaken to observe changes that influence CR in the secondary prevention
      of cerebral infarction (CI). The study included 56 cases at high risk of stroke
      (HRS), 147 cases of CI and 68 control subjects. The CI and HRS groups were
      divided into CR and NCR (none clopidogrel resistance) subgroups using standard
      criteria. The NCR group was subdivided into DCR (dynamic CR) and CNCR (continuous
      NCR) groups. Platelet aggregation rate (PAR) was assessed at baseline and after 2
      weeks treatment with clopidogrel 75 mg/day in the CI and HRS groups. In the NCR
      group, PAR was evaluated after 3 and 6 months of clopidogrel (75 mg/day)
      treatment. Baseline PAR was higher in the CI group than in the HRS or control
      groups (P < 0.01). The incidence of CR was 28.6 % in the CI and 13.6 % in the HRS
      group (P = 0.018). Diabetes mellitus, (OR 16.627; 95 % CI 4.691-58.934) and
      history of TIA (OR 13.711; 95 % CI 1.667-112.784) (both P < 0.05) were both
      associated with CR. Other independent risk factors included high total
      cholesterol, calcium antagonist or ACEI/ARB use. A total of 36 CR and 85 NCR
      cases completed 6 months follow-up. High total cholesterol was an independent
      risk factor for DCR (OR 0.415; 95 % CI 0.213-0.808; P = 0.01) which developed in
      15 subjects at 6 months. PAR decreased by >10 % after 2 weeks in 71.4 % of
      patients with CR who subsequently changed drugs or received combination therapy.
      Dynamic CR may occur after CI. Many factors including DM?TIA?HCT?P2Y12 epsilonC
      coexistence CYP2Y19 epsilonA?combination drug, associate CR or DCR. Our results
      highlight the need for PAR monitoring. 

PMID- 24136587
TI  - CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic
      protein-induced endothelial cell differentiation and vessel formation.
AB  - CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger
      domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a
      receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accumulated
      in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during
      their endothelial differentiation. CXXC5 overexpression induced Flk-1
      transcription in both endothelium-differentiated mESCs and human umbilical vein
      endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction
      of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif
      abolished transcriptional activity. We showed that bone morphorgenetic protein 4
      (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling
      suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4
      treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber
      formation (56.8 +/- 1.3% decrease, P<0.05) and migration (54.6 +/- 1.9% decrease,
      P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular
      development and angiogenesis were shown by specific defect of caudal vein plex
      vessel formation (57.9 +/- 11.8% decrease, P<0.05) in cxxc5 morpholino-injected
      zebrafish embryos and by suppression of BMP4-induced angiogenesis in
      subcutaneously injected Matrigel plugs in CXXC5(-/-) mice. Overall, CXXC5 is a
      transcriptional activator for Flk-1, mediating BMP signaling for differentiation
      and migration of endothelial cell and vessel formation.

PMID- 24136588
TI  - Correlative light and electron microscopic analyses of mitochondrial distribution
      in blastomeres of early fish embryos.
AB  - Early embryos of vertebrates undergo remarkable dynamic molecular events, such as
      embryonic gradient, cellular polarity, and asymmetry necessary for cell fate
      decisions. Correlative light and electron microscopy (CLEM) is a powerful tool to
      investigate rare or dynamic molecular events and has been developed for
      relatively small cells in culture and tissues but is not yet available for large
      cells of early development stage embryos. Here we report the capability of CLEM
      in blastomeres of medaka fish by using the mitochondria detection system. A short
      N-terminal signal peptide of the mitochondrial protein Tom20 was linked to green
      fluorescent protein (GFP), resulting in a fusion protein termed Tom20:GFP. The
      subcellular location of Tom20:GFP in medaka blastomeres reveals the lack of
      mitochondrial distribution in pseudopodia as well as inconspicuous redistribution
      during divisions. Blastomeres, after sample preparation procedures including high
      pressure freezing and freeze substitution, are able to preserve fluorescence,
      antigenicity, and fine structures, which allows for precise correlation between
      the Tom20:GFP fluorescence and mitochondria on merged light and electron
      micrographs. Furthermore, nanogold immunostaining for Tom20:GFP and endogenous
      Tom20 revealed their specific localization on the mitochondrial outer membrane.
      Our results extend the CLEM approach to early development stage embryos of a
      vertebrate.

PMID- 24136590
TI  - Overexpression of the polarity protein PAR-3 in clear cell renal cell carcinoma
      is associated with poor prognosis.
AB  - The partition-defective 3 (PAR-3) protein is implicated in the development and
      maintenance of cell polarity and is associated with proteins that mediate the
      changes in cytoskeleton organization required for cell polarity establishment. In
      this work, we used two original primary cell lines (R-180 and R-305) derived from
      clear cell Renal Cell Carcinoma (ccRCC) surgical specimens of a patient with
      unfavorable clinical course (R-180 cells) and a patient with favorable prognosis
      (R-305 cells) to identify genetic and molecular features that may explain the
      survival difference of the two patients. The cytogenetic analysis of these cell
      lines revealed that the PARD3 gene was amplified only in the R-180 cell line that
      was derived from an aggressive ccRCC. PARD3 gene amplification was associated
      with overexpression of the encoded protein and altered cytoskeleton organization.
      Consistently, PARD3 knockdown in R-180 cells restored the cytoskeleton
      organization and reduced cell migration in comparison to non-transfected cells.
      Immunohistochemical analysis of ccRCC samples from a cohort of 96 patients with a
      follow-up of 6 years revealed that PAR-3 overexpression was correlated with poor
      survival. Our results suggest that PAR-3 has a role in the clinical
      aggressiveness of ccRCC, possibly by promoting cell migration.

PMID- 24136589
TI  - Non-specific accumulation of glycosphingolipids in GNE myopathy.
AB  - BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) is a bifunctional enzyme
      responsible for the first committed steps in the synthesis of sialic acid, a
      common terminal monosaccharide in both protein and lipid glycosylation. GNE
      mutations are responsible for a rare autosomal recessive neuromuscular disorder,
      GNE myopathy (also called hereditary inclusion body myopathy). The connection
      between the impairment of sialic acid synthesis and muscle pathology in GNE
      myopathy remains poorly understood. METHODS: Glycosphingolipid (GSL) analysis was
      performed by HPLC in multiple models of GNE myopathy, including patients'
      fibroblasts and plasma, control fibroblasts with inhibited GNE epimerase activity
      through a novel imino sugar, and tissues of Gne(M712T/M712T) knock-in mice.
      RESULTS: Not only neutral GSLs, but also sialylated GSLs, were significantly
      increased compared to controls in all tested models of GNE myopathy. Treatment of
      GNE myopathy fibroblasts with N-acetylmannosamine (ManNAc), a sialic acid
      precursor downstream of GNE epimerase activity, ameliorated the increased total
      GSL concentrations. CONCLUSION: GNE myopathy models have increased total GSL
      concentrations. ManNAc supplementation results in decrease of GSL levels, linking
      abnormal increase of total GSLs in GNE myopathy to defects in the sialic acid
      biosynthetic pathway. These data advocate for further exploring GSL
      concentrations as an informative biomarker, not only for GNE myopathy, but also
      for other disorders of sialic acid metabolism.

PMID- 24136591
TI  - Patients infected with HIV are at high-risk for hepatitis E virus infection in
      Spain.
AB  - Hepatitis E virus is responsible for sporadic cases of acute, self-limited viral
      hepatitis not only in endemic but also in industrialized countries. In addition,
      some reports confirm that it can cause chronic infection and even cirrhosis in
      immunosuppressed and also in patients infected with HIV. There are few data about
      prevalence and incidence of HEV chronic infection in HIV-HEV coinfected
      individuals in Spain. The aim of this study is to investigate the prevalence of
      anti-HEV IgG in a representative sample of 448 patients infected with HIV and
      determine the role of age, gender, and CD4 counts in the detection of anti-HEV
      IgG antibodies in blood. In addition, the clinical features and ALT levels in
      relation to the presence of anti-HEV IgM and/or HEV-RNA in the blood of these
      patients were investigated. Anti-HEV IgG antibodies were detected in serum using
      a commercial enzyme immunoassay. All positive samples were studied further for
      the presence of anti-HEV IgM antibodies. In addition, HEV RNA was amplified by
      reverse transcriptase (RT)-nested PCR in all serum samples with IgM anti-HEV. The
      overall prevalence of anti-HEV IgG was 10.4% (45/448, 95% C.I. 7.2-12.8%). HEV
      RNA was found in only one patient out of the 45 anti-HEV IgG positive samples
      studied. Regarding to gender and CD4 count, no difference in seroprevalence could
      be observed. This prevalence data suggest that patients infected with HIV can be
      considered a risk group for HEV infection and that chronic coinfection HEV-HIV
      seems to be a very rare event.

PMID- 24136592
TI  - Bi-directional-bi-dimensionality alignment of self-supporting Mn3O4 nanorod and
      nanotube arrays with different bacteriostasis and magnetism.
AB  - Self-supported Mn3O4 patterns of aligned nanorods and nanotubes were synthesized
      through a bi-directional-bi-dimensionality growth model by using sodium gluconate
      and urea as additives under mild hydrothermal conditions without the use of any
      substrates. In one direction, Mn3O4 grows to form one-dimensional nanorods or
      nanotubes, while in the other direction Mn3O4 grows into two-dimensional
      nanoplates to support the nanorods or nanotubes to align into arrays. These two
      kinds of new nanostructures, a nanotube pattern and a nanorod pattern, show
      similar and good bacteriostasis for Gram positive bacteria, but for Gram negative
      bacteria the nanotube pattern shows much better bacterial restraint than the
      nanorod pattern. Magnetic studies show that the nanorod arrays display similar
      magnetic properties to the commercial Mn3O4, while the nanotube arrays show
      different ferromagnetic behaviors with enhanced remnant magnetization and
      saturation magnetization (Ms) at low temperature. 

PMID- 24136593
TI  - A novel mouse model of trauma induced heterotopic ossification.
AB  - Severe soft tissue trauma is associated with heterotopic ossification (HO), the
      abnormal deposition of bone at extra-skeletal sites. The pathophysiology of the
      development of trauma-induced HO remains largely unknown due in part to the lack
      of appropriate animal models. In this study, we sought to develop a new trauma
      induced HO mouse model using muscle impact injury combined with low dose BMP-2.
      BMP-2 at doses ranging from 0 to 2 ug was injected into quadriceps muscles of
      adult male C57/BL6 mice. Animals then received a one-time quadriceps impaction
      injury to mimic the trauma associated with severe injuries. HO was monitored
      using in vivo microCT scanning at 1, 2, 4, and 8 weeks after treatment. After
      trauma, the expression of BMP-2, -4, BMP receptor 1, SOX9 and RUNX2 were
      increased in muscle. Although little or no HO was observed in mice receiving 1 ug
      BMP-2, combining this dose with muscle trauma produced an abundance of HO. At
      higher doses of BMP-2, trauma did not augment mineral deposition. These results
      suggest that BMP-2 signaling can sensitize muscle to trauma-induced HO. They also
      provide the basis for a new model to study the pathogenesis of trauma-induced HO.

PMID- 24136594
TI  - Prophylactic administration of non-organophosphate cholinesterase inhibitors
      before acute exposure to organophosphates: assessment using terbufos sulfone.
AB  - Poisoning with organophosphorus compounds (OPCs) poses a serious threat
      worldwide. OPC-induced mortality can be significantly reduced by prophylactic
      administration of reversible acetylcholinesterase (AChE) inhibitors. The only
      American Food and Drug Administration (FDA)-approved substance for such pre
      treatment (to soman exposure) is presently pyridostigmine, although its efficacy
      is controversial. In search for more efficacious and broad-spectrum alternatives,
      we have assessed in vivo the mortality-reducing efficacy of a group of five
      compounds with known AChE inhibitory activity (pyridostigmine, physostigmine,
      ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30
      min before exposure to the OPC terbufos sulfone. Protection was quantified in
      rats by determining the relative risk of death (RR) using Cox analysis, with RR =
      1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE
      inhibitors reduced terbufos sulfone-induced mortality significantly (p <= 0.05)
      as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in
      vivo protection from terbufos sulfone-induced mortality was achieved, when K-27
      was given before terbufos sulfone exposure (RR = 0.06), which was significantly
      (P <= 0.05) superior to the pre-treatment with all other tested compounds, for
      example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR =
      0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine,
      pyridostigmine, physostigmine and ranitidine were not statistically significant.
      Prophylactic administration of an oxime (such as K-27) in case of imminent OPC
      exposure may be a viable option.

PMID- 24136595
TI  - Predicting RNA structure: advances and limitations.
AB  - RNA secondary structures can be predicted using efficient algorithms. A widely
      used software package implementing a large number of computational methods is the
      ViennaRNA Package. This chapter describes how to use programs from the ViennaRNA
      Package to perform common tasks such as prediction of minimum free-energy
      structures, suboptimal structures, or base pairing probabilities, and generating
      secondary structure plots with reliability annotation. Moreover, we present
      recent methods to assess the folding kinetics of an RNA via 2D projections of the
      energy landscape, identification of local minima and energy barriers, or
      simulation of RNA folding as a Markov process. 

PMID- 24136596
TI  - cis-Acting 5' hammerhead ribozyme optimization for in vitro transcription of
      highly structured RNAs.
AB  - RNA-mediated biological processes usually require precise definition of 5' and 3'
      ends. RNA ends obtained by in vitro transcription using T7 RNA polymerase are
      often heterogeneous in length and sequence. An efficient strategy to overcome
      these drawbacks consists of inserting an RNA with known boundaries in between two
      ribozymes, usually a 5' hammerhead and a 3' hepatitis delta virus ribozymes, that
      cleave off the desired RNA. In practice, folding of the three RNAs challenges
      each other, potentially preventing thorough processing. Folding and cleavage of
      the 5' hammerhead ribozyme relies on a sequence of nucleotides belonging to the
      central RNA making it more sensitive than the usual 3' hepatitis delta virus
      ribozyme. The intrinsic stability of the central RNA may thus prevent correct
      processing of the full transcript. Here, we present a method in which
      incorporation of a full-length hammerhead ribozyme with a specific tertiary
      interaction prevents alternative folding with the lariat capping GIR1 ribozyme
      and enables complete cleavage in the course of the transcription. This strategy
      may be transposable for in vitro transcription of any highly structured RNA. 

PMID- 24136597
TI  - RNA structural analysis by enzymatic digestion.
AB  - Enzymatic probing is a rapid, straightforward method for determining which
      regions of a folded RNA are structurally constrained. It can be carried out using
      very small amounts of material, and is especially suitable for short RNAs. Here
      we report a protocol that we have found to be useful and readily adaptable to the
      evaluation of RNAs up to 150-200 nucleotides in length. Considerations for
      optimization are also included. In brief, the method includes folding end-labeled
      RNA into its native conformation, partial digestion with structure-sensitive
      nucleases, and identification of the cleavage sites by electrophoretic separation
      of the cleavage fragments. 

PMID- 24136598
TI  - The mutate-and-map protocol for inferring base pairs in structured RNA.
AB  - Chemical mapping is a widespread technique for structural analysis of nucleic
      acids in which a molecule's reactivity to different probes is quantified at
      single nucleotide resolution and used to constrain structural modeling. This
      experimental framework has been extensively revisited in the past decade with new
      strategies for high-throughput readouts, chemical modification, and rapid data
      analysis. Recently, we have coupled the technique to high-throughput mutagenesis.
      Point mutations of a base paired nucleotide can lead to exposure of not only that
      nucleotide but also its interaction partner. Systematically carrying out the
      mutation and mapping for the entire system gives an experimental approximation of
      the molecule's "contact map." Here, we give our in-house protocol for this
      "mutate-and-map" (M2) strategy, based on 96-well capillary electrophoresis, and
      we provide practical tips on interpreting the data to infer nucleic acid
      structure. 

PMID- 24136599
TI  - Mapping RNA structure in vitro using nucleobase-specific probes.
AB  - RNAs have to adopt specific three-dimensional structures to fulfill their
      biological functions. Therefore exploring RNA structure is of interest to
      understand RNA-dependent processes. Chemical probing in vitro is a very powerful
      tool to investigate RNA molecules under a variety of conditions. Among the most
      frequently used chemical reagents are the nucleobase-specific probes dimethyl
      sulfate (DMS), 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p
      toluenesulfonate (CMCT) and beta-ethoxy-alpha-ketobutyraldehyde (kethoxal). These
      chemical reagents modify nucleotides which are not involved in hydrogen bonding
      or protected by a ligand, such as proteins or metabolites. Upon performing
      modification reactions with all three chemicals the accessibility of all four
      nucleobases can be determined. With this fast and inexpensive method local
      changes in RNA secondary and tertiary structure, as well as the formation of
      contacts between RNA and its ligands can be detected independent of the RNA's
      length. 

PMID- 24136600
TI  - Massively parallel RNA chemical mapping with a reduced bias MAP-seq protocol.
AB  - Chemical mapping methods probe RNA structure by revealing and leveraging
      correlations of a nucleotide's structural accessibility or flexibility with its
      reactivity to various chemical probes. Pioneering work by Lucks and colleagues
      has expanded this method to probe hundreds of molecules at once on an Illumina
      sequencing platform, obviating the use of slab gels or capillary electrophoresis
      on one molecule at a time. Here, we describe optimizations to this method from
      our lab, resulting in the MAP-seq protocol (Multiplexed Accessibility Probing
      read out through sequencing), version 1.0. The protocol permits the quantitative
      probing of thousands of RNAs at once, by several chemical modification reagents,
      on the time scale of a day using a tabletop Illumina machine. This method and a
      software package MAPseeker ( http://simtk.org/home/map_seeker ) address several
      potential sources of bias, by eliminating PCR steps, improving ligation
      efficiencies of ssDNA adapters, and avoiding problematic heuristics in prior
      algorithms. We hope that the step-by-step description of MAP-seq 1.0 will help
      other RNA mapping laboratories to transition from electrophoretic to next
      generation sequencing methods and to further reduce the turnaround time and any
      remaining biases of the protocol. 

PMID- 24136601
TI  - Probing RNA folding by hydroxyl radical footprinting.
AB  - In recent years RNA molecules have emerged as central players in the regulation
      of gene expression. Many of these noncoding RNAs possess well-defined, complex,
      three-dimensional structures which are essential for their biological function.
      In this context, much effort has been devoted to develop computational and
      experimental techniques for RNA structure determination. Among available
      experimental tools to investigate the higher-order folding of structured RNAs,
      hydroxyl radical probing stands as one of the most informative and reliable ones.
      Hydroxyl radicals are oxidative species that cleave the nucleic acid backbone
      solely according to the solvent accessibility of individual phosphodiester bonds,
      with no sequence or secondary structure specificity. Therefore, the cleavage
      pattern obtained directly reflects the degree of protection/exposure to the
      solvent of each section of the molecule under inspection, providing valuable
      information about how these different sections interact together to form the
      final three-dimensional architecture. In this chapter we describe a robust,
      accurate and very sensitive hydroxyl radical probing method that can be applied
      to any structured RNA molecule and is suitable to investigate RNA folding and RNA
      conformational changes induced by binding of a ligand. 

PMID- 24136602
TI  - Monitoring global structural changes and specific metal-ion-binding sites in RNA
      by in-line probing and Tb(III) cleavage.
AB  - In this chapter we describe the use of two methods, in-line probing as well as
      terbium(III) cleavage. Both methods can be applied to RNAs of any size,
      structure, and function. Aside from revealing directly metal ion-binding sites
      these techniques also provide structural information for longer RNA sequences
      that are out of range to be analyzed with other techniques such as NMR. The
      cleavage pattern derived from in-line probing experiments reflects local and
      overall conformational changes in RNA upon the addition of metal ions, metal
      complexes, or other ligands. On the other side, terbium(III) cleavage experiments
      are applied to locate specific metal ion-binding sites in RNA molecules. 

PMID- 24136603
TI  - Chemical probing of RNA in living cells.
AB  - RNAs need to adopt a specific architecture to exert their task in cells. While
      significant progress has been made in describing RNA folding landscapes in vitro,
      understanding intracellular RNA structure formation is still in its infancy. This
      is in part due to the complex nature of the cellular environment but also to the
      limited availability of suitable methodologies. To assess the intracellular
      structure of large RNAs, we recently applied a chemical probing technique and a
      metal-induced cleavage assay in vivo. These methods are based on the fact that
      small molecules, like dimethyl sulfate (DMS), or metal ions, such as Pb(2+),
      penetrate and spread throughout the cell very fast. Hence, these chemicals are
      able to modify accessible RNA residues or to induce cleavage of the RNA strand in
      the vicinity of a metal ion in living cells. Mapping of these incidents allows
      inferring information on the intracellular conformation, metal ion binding sites
      or ligand-induced structural changes of the respective RNA molecule. Importantly,
      in vivo chemical probing can be easily adapted to study RNAs in different cell
      types. 

PMID- 24136604
TI  - A chemogenetic approach to study the structural basis of protein-facilitated RNA
      folding.
AB  - Large RNA molecules play important roles in all aspects of cellular metabolism
      ranging from mRNA splicing and protein biosynthesis to regulation of gene
      expression. In order to correctly perform its function in the cell, an RNA
      molecule must fold into a complex tertiary structure. Folding of many large RNAs
      is slow either due to formation of stable misfolded intermediates or due to high
      contact order or instability of obligate folding intermediates. Therefore many
      RNAs use protein cofactors to facilitate their folding in vivo. Folding of the
      yeast mitochondrial group II intron ai5gamma to the native state under
      physiological conditions is facilitated by the protein cofactor Mss116. This
      chapter describes the use of Nucleotide Analog Interference Mapping (NAIM) to
      identify specific substructures within the intron molecule that are directly
      affected by the protein. 

PMID- 24136605
TI  - Applying UV crosslinking to study RNA-protein interactions in multicomponent
      ribonucleoprotein complexes.
AB  - Ribonucleoprotein complexes (RNPs) play crucial roles in a wide range of
      biological processes. Here, we describe experimental approaches to the UV
      crosslinking-based identification of protein-binding sites on RNA, using
      multicomponent Saccharomyces cerevisiae RNPs of the RNase P/MRP family as an
      example. To identify the binding sites of a protein component of interest, a
      hexahistidine affinity tag was fused to that protein. Then RNase P/MRP RNPs were
      purified from yeast cells that had expressed the protein component of interest
      with the fused tag, subjected to UV crosslinking, and disassembled to separate
      the non-covalently-bound components. The protein component of interest was
      isolated under denaturing conditions using the hexahistidine tag as a
      purification handle. Provided that the isolated protein formed UV-induced
      crosslinks with the RNA component of the studied RNP, the isolation of the
      protein resulted in the co-isolation of the covalently bound RNP RNA. The
      isolated protein was enzymatically degraded, and the UV crosslinked RNA was
      purified. The locations of the crosslinks formed between the protein component of
      interest and the RNP RNA were identified by primer extension with a reverse
      transcriptase followed by gel electrophoresis; this procedure was repeated for
      all of the protein components of RNases P/MRP. 

PMID- 24136606
TI  - The kinetics of ribozyme cleavage: a tool to analyze RNA folding as a function of
      catalysis.
AB  - As catalytically active RNAs, ribozymes can be characterized by kinetic
      measurements similar to classical enzyme kinetics. However, in contrast to
      standard protein enzymes, for which reactions can usually be started by mixing
      the enzyme with its substrate, ribozymes are typically self-cleaving. The
      reaction has to be initiated by folding the RNA into its active conformation.
      Thus, ribozyme kinetics are influenced by both folding and catalytic components
      and often enable indirect observation of RNA folding. Here, I describe how to
      obtain quantitative ribozyme cleavage data via denaturing polyacrylamide gel
      electrophoresis (PAGE) of radioactively labeled in vitro transcripts and discuss
      general considerations for subsequent kinetic analysis. 

PMID- 24136607
TI  - RNA catalytic activity as a probe of chaperone-mediated RNA folding.
AB  - For structured RNAs that possess catalytic activity, this activity provides a
      powerful probe for measuring the progress of folding and the effects of RNA
      chaperone proteins on the folding rate. The crux of this approach is that only
      the natively folded RNA is able to perform the catalytic reaction. This method
      can provide a quantitative measure of the fraction of native RNA over time, and
      it can readily distinguish the native state from all misfolded conformations.
      Here we describe an activity-based method measuring native folding of ribozymes
      derived from self-splicing group I introns, and we show how the assay can be used
      to monitor acceleration of native folding by DEAD-box RNA helicase proteins that
      function as general RNA chaperones. By measuring the amount of substrate that is
      converted to product in a rapid first turnover, we describe how to determine the
      fraction of the ribozyme population that is present in the native state. Further,
      we describe how to perform a two-stage or discontinuous assay in which folding
      proceeds in stage one and then solution conditions are changed in stage two to
      permit catalytic activity and block further folding. This protocol allows folding
      to be followed under a broad range of solution conditions, including those that
      do not support catalytic activity, and facilitates studies of chaperone proteins.

PMID- 24136608
TI  - Evaluation of RNA chaperone activity in vivo and in vitro using misfolded group I
      ribozymes.
AB  - Here two methods to measure RNA chaperone activity in vivo and in vitro are
      described. In both assays folding of a misfolded group I intron RNA into the
      splicing-competent form in the presence of proteins with RNA chaperone activity
      is measured. Folding is evaluated indirectly by assessing the difference in
      splicing activity with or without proteins with RNA chaperone activity. In vitro,
      we use the thymidylate synthase (td) group I intron of phage T4 that is split
      into two halves. As a consequence this split ribozyme is only capable to fold and
      in turn to splice in trans at elevated temperatures. Proteins with RNA chaperone
      activity enable splicing of the split intron at lower temperatures. This
      difference in splicing activity is measured to assess the efficacy of the RNA
      chaperone. In vivo, a mutant variant of the td group I intron is trapped in a
      misfolded conformation, resulting in a reduced splicing activity. Over-expression
      of proteins with RNA chaperone activity results in an increase in splicing in
      vivo, as these proteins resolve the misfolded conformation. 

PMID- 24136609
TI  - RNA conformational changes analyzed by comparative gel electrophoresis.
AB  - The study of biologically relevant native RNA structures is important to
      understand their cellular function(s). Native gel electrophoresis provides
      information about such native structures in solution as a function of
      experimental conditions. The application of native gel electrophoresis in a
      comparative manner allows to obtain precise information on relative angles
      subtended between given pair of stems in an RNA molecule. By adapting this
      approach, it is possible to obtain very specific structural information such as
      the amplitude of dihedral angles and helical rotation. As an example, we will
      describe how native gel electrophoresis can be used to study the folding of the S
      adenosylmethionine (SAM) sensing riboswitch. 

PMID- 24136610
TI  - Detecting RNA tertiary folding by sedimentation velocity analytical
      ultracentrifugation.
AB  - Analytical Ultracentrifugation (AUC) is a highly sensitive technique for
      detecting global conformational features of biological molecules and molecular
      interactions in solution. When operated in a sedimentation velocity (SV)
      recording mode, it reports precisely on the hydrodynamic properties of a
      molecule, including its sedimentation and diffusion coefficients, which can be
      used to calculate its hydrated radius, as well as, to estimate its global shape.
      This chapter describes the application of SV-AUC to the detection of global
      conformational changes accompanying equilibrium counterion induced tertiary
      folding of structured RNA molecules. A brief theoretical background is provided
      at the beginning, aimed at familiarizing the readers with the operational
      principle of the technique; then, a detailed set of instructions is provided on
      how to design, conduct, and analyze the data from an equilibrium RNA folding
      experiment, using SV-AUC. 

PMID- 24136611
TI  - RNA folding dynamics using laser-assisted single-molecule refolding.
AB  - RNA folding pathways can be complex and even include kinetic traps or misfolded
      intermediates that can be slow to resolve. Characterizing these pathways is
      critical to understanding how RNA molecules acquire their biological function. We
      have previously developed a novel approach to help characterize such misfolded
      intermediates. Laser-assisted single-molecule refolding (LASR) is a powerful
      technique that combines temperature-jump (T-jump) kinetics with single-molecule
      detection. In a typical LASR experiment, the temperature is rapidly increased and
      conformational dynamics are characterized, in real-time, at the single-molecule
      level using single-molecule fluorescence resonance energy transfer (smFRET).
      Here, we provide detailed protocols for performing LASR experiments including
      sample preparation, temperature calibration, and data analysis. 

PMID- 24136612
TI  - RNA refolding studied by light-coupled NMR spectroscopy.
AB  - Conformational transitions (refolding) between long-lived conformational states
      constitute the time-limiting step during the folding process of large RNAs. As
      the dynamics of these reactions dominate the regulatory and other functional
      behavior of RNA molecules, it is of importance to characterize them with high
      spatial and temporal resolution. Here, we describe a method for the investigation
      of RNA refolding reactions based on the photolytic generation of preselected
      conformations in a non-equilibrium state, followed by the observation of the
      folding trajectory with real-time NMR spectroscopy. 

PMID- 24136613
TI  - Exploring RNA oligomerization and ligand binding by fluorescence correlation
      spectroscopy and small angle X-ray scattering.
AB  - RNA forms defined structures and binds specifically to target molecules. The
      combination of data which results from fluorescence correlation spectroscopy
      (FCS) and small angle X-ray scattering (SAXS) measurements can be used to
      determine intermolecular interactions between RNA and its binding partners. To
      define oligomerization states of free RNA and its complexes with bound target
      molecules, hydrodynamic radii, radii of gyration as well as the maximum sizes of
      the components have to be determined and compared. Furthermore, the program
      OLIGOMER allows calculating the portions of monomeric and dimeric RNA, for
      instance, within a mixture. 

PMID- 24136614
TI  - Large in-plane deformation of RuO6 octahedron and ferromagnetism of bulk SrRuO3.
AB  - SrRuO3 is a ferromagnetic metal with several unusual physical properties such as
      zero thermal expansion below Tc, so-called Invar behavior. Another anomalous
      feature is that the a-axis lattice constant is larger than the b-axis lattice
      constant, a clear deviation from the predictions of the Glazer structural
      description with rigid RuO6 octahedron motion. Using high resolution neutron
      diffraction techniques, we show how these two structural anomalies arise from the
      irregular in-plane deformation, i.e. plastic behavior of the RuO6 octahedron, a
      weak band Jahn-Teller distortion. We further demonstrate that the ferromagnetic
      instability of SrRuO3 is related to the temperature-induced localization of Ru 4d
      bands. 

PMID- 24136615
TI  - Finding common ground.

PMID- 24136617
TI  - ACMG statement on access to reproductive options after prenatal diagnosis.

PMID- 24136616
TI  - Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN
      Lom/CMT4D.
AB  - PURPOSE: Copy-number variations as a mutational mechanism contribute
      significantly to human disease. Approximately one-half of the patients with
      Charcot-Marie-Tooth (CMT) disease have a 1.4 Mb duplication copy-number variation
      as the cause of their neuropathy. However, non-CMT1A neuropathy patients rarely
      have causative copy-number variations, and to date, autosomal-recessive disease
      has not been associated with copy-number variation as a mutational mechanism.
      METHODS: We performed Agilent 8 * 60 K array comparative genomic hybridization on
      DNA from 12 recessive Turkish families with CMT disease. Additional molecular
      studies were conducted to detect breakpoint junctions and to evaluate gene
      expression levels in a family in which we detected an intragenic duplication copy
      number variation. RESULTS: We detected an ~6.25 kb homozygous intragenic
      duplication in NDRG1, a gene known to be causative for recessive HMSNL/CMT4D, in
      three individuals from a Turkish family with CMT neuropathy. Further studies
      showed that this intragenic copy-number variation resulted in a homozygous
      duplication of exons 6-8 that caused decreased mRNA expression of NDRG1.
      CONCLUSION: Exon-focused high-resolution array comparative genomic hybridization
      enables the detection of copy-number variation carrier states in recessive genes,
      particularly small copy-number variations encompassing or disrupting single
      genes. In families for whom a molecular diagnosis has not been elucidated by
      conventional clinical assays, an assessment for copy-number variations in known
      CMT genes might be considered.

PMID- 24136618
TI  - 22q13.2q13.32 genomic regions associated with severity of speech delay,
      developmental delay, and physical features in Phelan-McDermid syndrome.
AB  - PURPOSE: Phelan-McDermid syndrome is a developmental disability syndrome with
      varying deletions of 22q13 and varying clinical severity. We tested the
      hypothesis that, in addition to loss of the telomeric gene SHANK3, specific
      genomic regions within 22q13 are associated with important clinical features.
      METHODS: We used a customized oligo array comparative genomic hybridization of
      22q12.3-terminus to obtain deletion breakpoints in a cohort of 70 patients with
      terminal 22q13 deletions. We used association and receiver operating
      characteristic statistical methods in a novel manner and also incorporated
      protein interaction networks to identify 22q13 genomic locations and genes
      associated with clinical features. RESULTS: Specific genomic regions and
      candidate genes within 22q13.2q13.32 were associated with severity of
      speech/language delay, neonatal hypotonia, delayed age at walking, hair-pulling
      behaviors, male genital anomalies, dysplastic toenails, large/fleshy hands,
      macrocephaly, short and tall stature, facial asymmetry, and atypical reflexes. We
      also found regions suggestive of a negative association with autism spectrum
      disorders. CONCLUSION: This work advances the field of research beyond the
      observation of a correlation between deletion size and phenotype and identifies
      candidate 22q13 loci, and in some cases specific genes, associated with singular
      clinical features observed in Phelan-McDermid syndrome. Our statistical approach
      may be useful in genotype-phenotype analyses for other microdeletion or
      microduplication syndromes.

PMID- 24136619
TI  - Opportunities to improve recruitment into medical genetics residency programs:
      survey results of program directors and medical genetics residents.
AB  - PURPOSE: Approximately 50% of medical genetics residency positions remain
      unfilled each year. This study was designed to assess current recruitment
      strategies used by program directors, to identify factors that influenced
      trainees to choose medical genetics as a career, and to use these results as a
      foundation to develop a strategic plan to address the challenges of recruitment.
      METHODS: Two surveys were created, one for program directors and one for current
      medical genetics residents, to evaluate current recruiting efforts and
      institutional support for programs and to identify factors that helped trainees
      choose genetics as a career. RESULTS: Program directors identified the most
      successful recruiting methods as "direct contact with residents or medical
      students" and "word of mouth" (80%). Residents listed having a mentor (50%),
      previous research in genetics (35%), and genetics coursework (33%) as the top
      reasons that influenced them to enter the field. CONCLUSION: Geneticists should
      become more proactive in providing resources to students to help them understand
      a career as a medical geneticist and mentor those students/residents who show
      true interest in the field. Results of these surveys spurred the development of
      the Task Force on Medical Genetics Education and Training of the American College
      of Medical Genetics and Genomics.

PMID- 24136620
TI  - Phenotypic consequences in black South African Fanconi anemia patients homozygous
      for a founder mutation.
AB  - PURPOSE: Fanconi anemia is a genotypically and phenotypically heterogeneous
      condition, characterized microscopically by chromosomal instability and breakage.
      Affected individuals manifest growth restriction and congenital physical
      abnormalities; most progress to hematological disease including bone marrow
      aplasia. Black South African Fanconi anemia patients share a common causative
      founder mutation in the Fanconi G gene in 80% of cases (637_643delTACCGCC). The
      aim of this study was to investigate the genotype-physical phenotype correlation
      in a cohort of individuals homozygous for this mutation. METHODS: Thirty-five
      black patients were recruited from tertiary level hematology/oncology clinics in
      South Africa. Participants were subjected to a comprehensive clinical
      examination, documenting growth, congenital anomalies, and phenotypic
      variability. RESULTS: Descriptive statistical analysis showed significant growth
      abnormalities in many patients and a high frequency (97%) of skin pigmentary
      anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently
      (>=70%). Apart from malformations of the kidney (in 37%) and gastrointestinal
      tract (in 8.5%), congenital anomalies of other systems including the
      cardiovascular and central nervous systems, genitalia, and vertebrae were
      infrequent (<5%). CONCLUSION: The diagnosis of Fanconi anemia in black South
      African patients before the onset of hematological symptoms remains a clinical
      challenge, with the physical phenotype unlikely to be recognized by those without
      dysmorphology expertise.

PMID- 24136622
TI  - T cell responses: a dendritic cell designed for two.

PMID- 24136621
TI  - Contractile responses to rat urotensin II in resting and depolarized basilar
      arteries.
AB  - The effects of human urotensin II (hUII) on the vascular tone of different animal
      species has been studied extensively. However, little has been reported on the
      vasoactive effects of rat urotensin (rUII) in murine models. The aim of the
      present study was to investigate the effects of rUII on vasoreactivity in rat
      basilar arteries. Basilar arteries from adult male Wistar rats (300-350 g) were
      isolated, cut in rings, and mounted on a small vessel myograph to measure
      isometric tension. rUII concentrations were studied in both resting and
      depolarized state. To remove endothelial nitric oxide effects from the rUII
      response, we treated selected arterial rings with Nomega-nitro-L-arginine methyl
      ester (L-NAME). 10 MUM rUII produced a potent vasoconstrictor response in rat
      basilar arteries with intact endothelium, while isometric forces remained
      unaffected in arterial rings treated with lower rUII concentrations. Although L
      NAME did not have a significant effect on 10 MUM rUII-evoked contraction, it
      slightly increased arterial ring contraction elicited by 1 MUM rUII. In
      depolarized arteries, dose-dependent rUII increased depolarization-induced
      contractions. This effect was suppressed by L-NAME. Our results show that the rat
      basilar artery has a vasoconstrictor response to rUII. The most potent
      vasoconstrictor effect was produced by lower doses of rUII (0.1 and 1 MUM) in
      depolarized arteries with intact endothelium. This effect could facilitate
      arterial vasospasm in vascular pathophysiological processes such as subarachnoid
      hemorrhage and hypertension, when sustained depolarization and L-type Ca(2+)
      channel activation are present.

PMID- 24136623
TI  - The removal of the bereavement exclusion in the DSM-5: exploring the evidence.
AB  - Since 1980, the DSM-III and its various iterations through the DSM-IV-TR have
      systematically excluded individuals from the diagnosis of major depressive
      disorder if symptoms began within months after the death of a loved one (2 months
      in DSM-IV), unless the depressive syndrome was 'severely' impairing and/or
      accompanied by specific features. This criterion became known as the 'bereavement
      exclusion'. No other adverse life events were noted to negate the diagnosis of
      major depressive disorder if all other symptomatic, duration, severity and
      distress/impairment criteria were met. However, studies since the inception of
      the bereavement exclusion have shown that depressive syndromes occurring after
      bereavement share many of the same features as other, non-bereavement related
      depressions, tend to be chronic and/or recurrent if left untreated, interfere
      with the resolution of grief, and respond to treatment. Furthermore, the
      bereavement exclusion has had the unintended consequence of suggesting that grief
      should end in only 2 months, or that grief and major depressive disorder cannot
      co-occur. To prevent the denial of diagnosis and the consideration of sometimes
      much needed care, even after bereavement or other significant losses, the DSM-5
      no longer contains the bereavement exclusion. Instead, the DSM-5 now permits the
      diagnosis of major depressive disorder after and during bereavement and includes
      a note and a comprehensive footnote in the major depressive episode criteria set
      to guide clinicians in making the diagnosis in this context. The decision to make
      this change was widely and publically debated and remains controversial. This
      article reports on the rationale for this decision and the way the DSM-5 now
      addresses the challenges of diagnosing major depressive disorder in the context
      of someone grieving the loss of a loved one.

PMID- 24136624
TI  - Recent trends in epistaxis management in the United States: 2008-2010.
AB  - IMPORTANCE: The treatment of epistaxis is variable. It is important to analyze
      the effect of the available interventions on patient outcomes. OBJECTIVE: To
      determine demographic, management, and outcome trends in patients admitted with a
      primary diagnosis of epistaxis and treated with conservative management, nasal
      packing, arterial ligation, or embolization. DESIGN, SETTING, AND PARTICIPANTS: A
      review of the data reported by hospitals to the 2008-2010 Nationwide Inpatient
      Sample for patients admitted with a primary diagnosis of epistaxis was conducted.
      INTERVENTIONS: Conservative management, nasal packing, arterial ligation, or
      embolization for epistaxis control. MAIN OUTCOMES AND MEASURES: Descriptive
      statistics for hospital and patient demographic data. Multivariate models were
      constructed to compare treatment modalities, controlling for patient- and
      hospital-level variation while reporting the treatment outcomes of mortality,
      stroke, blindness, length of stay, and total cost. Comparisons were made between
      patients undergoing embolization, surgical ligation, or nasal packing.
      Descriptive statistics for patients treated conservatively are reported. RESULTS:
      A total of 57, 039 cases of primary epistaxis were identified. Of these, 21, 872
      patients (38.3%) were treated conservatively, 30, 389 (53.3%) received nasal
      packing or cauterization, 2706 (4.7%) underwent arterial ligation, and 1956
      (3.4%) underwent embolization The odds of stroke in patients following
      embolization were significantly higher than in patients who underwent nasal
      packing (odds ratio, 4.660; P = .003), with no significant difference seen
      compared with surgical ligation (P = .70). There were no significant differences
      in the odds of mortality or blindness between any of the study groups. Patients
      undergoing embolization incurred the highest total hospital costs, nearly
      doubling the cost of ligation (P < .001), without a corresponding increase in the
      length of hospital stay (P = .20). CONCLUSIONS AND RELEVANCE: Treatment for
      epistaxis is highly variable. No significant differences in clinical outcomes
      were noted between arterial ligation and embolization in the population studied,
      although embolization resulted in significantly higher costs. Further prospective
      studies are needed to elucidate variables affecting outcomes of the various
      treatment options for epistaxis.

PMID- 24136625
TI  - Single and fused transgenic Bacillus thuringiensis rice alter the species
      specific responses of non-target planthoppers to elevated carbon dioxide and
      temperature.
AB  - BACKGROUND: The approval of transgenic Bacillus thuringiensis (Bt) rice by China
      was momentous for biotech crops, although it has yet to be approved for
      commercial production. Non-target pest problems in rice paddies, such as the
      three ecologically similar species of planthoppers Nilaparvata lugens, Laodelphax
      striatellus and Sogatella furcifera, could become increasingly serious under
      global climate change. Fused (Cry1Ab/Cry1Ac) and single (Cry1Ab) transgenic Bt
      rice were evaluated for effects on species-specific responses of planthoppers to
      elevated carbon dioxide (CO2) and temperature. RESULTS: Transgenic Bt rice lines
      significantly modified species-specific responses of the planthoppers to elevated
      CO2 and temperature. High temperature appears to favour outbreaks of S. furcifera
      relative to N. lugens and L. striatellus when feeding upon fused transgenic Bt
      rice, especially at elevated CO2 . Elevated CO2 at high temperature appears to be
      a factor reducing S. furcifera occurrence when feeding upon single transgenic Bt
      rice. CONCLUSION: Different types of transgenic Bt rice alter the species
      specific responses of non-target planthoppers to elevated CO2 and temperature.
      Compared with their non-transgenic parental lines, the single transgenic Bt rice
      shows better performance in controlling the non-target planthopper S. furcifera
      by comparison with the fused transgenic Bt rice under elevated CO2 and
      temperature. It is suggested that multitypes of transgenic Bt rice be used in the
      field simultaneously in order to take advantage of high transgenic diversity for
      optimal performance against all pests in paddy fields.

PMID- 24136626
TI  - From victim to victor: "breaking bad" and the dark potential of the terminally
      empowered.
AB  - As treatments for malignancies have improved incrementally over the preceding
      decades, patients with cancer have been encouraged to reject an attitude of
      hopelessness and to choose instead the role of fighters. The recasting of the
      cancer patient as warrior and winner, upheld through the Livestrong movement,
      reaches its monstrous apotheosis in the form of Walter White, the central figure
      in the AMC television series "Breaking Bad." The story begins with Walt as the
      protagonist, but the arc of this conversion narrative transforms him into the
      antagonist, exploring the darkest potential of his post-diagnosis empowerment.
      His awareness of his own mortality enables him to take risks that his more
      rational, pre-cancer self would have avoided. Rather than being rendered impotent
      by fear of an impending death, he finds himself emboldened, liberated from
      behavioral norms, capable of heretofore-unthinkable violence and even murder. As
      Walt moves from victim to victor, the viewer realizes the perils of a survive-at
      all-costs mentality and is forced to question their own, initially sympathetic
      perception of Walt. The series subverts the notion of the cancer patient made
      noble through struggle by portraying a man betrayed by his own body who then
      becomes willing to betray everything else in the amoral service of his pride. 

PMID- 24136628
TI  - Comparison of spectral-domain and high-penetration OCT for observing morphologic
      changes in age-related macular degeneration and polypoidal choroidal
      vasculopathy.
AB  - BACKGROUND: We compared the visibility of retinal and choroidal pathologies using
      high-penetration optical coherence tomography (HP-OCT) with a long-wavelength
      light source (1,050 nm) and conventional spectral-domain OCT (SD-OCT) in age
      related macular degeneration (AMD). METHODS: One hundred and forty-six eyes were
      included: 63 eyes with AMD, 79 eyes with polypoidal choroidal vasculopathy (PCV),
      and four eyes with retinal angiomatous proliferation. The SD-OCT and HP-OCT
      images were compared using the grading criteria to grade the visibility of the
      retinal changes, the line corresponding to the retinal pigment epithelium (RPE),
      and the chorioscleral interface (CSI). In 132 eyes with a pigment epithelial
      detachment (PED), we graded the structures inside the PED, Bruch's line, and the
      CSI. We compared the visibility of those changes in eyes with subretinal
      hyperreflective changes due to a subretinal hemorrhage (SRH) (n = 17) or a
      hemorrhage inside the PED (HPED) (n = 12). RESULTS: HP-OCT provided superior
      visibility of the following structures compared to SD-OCT (P < 0.01): the CSI,
      structures inside the PED, Bruch's line inside the PED, the CSI inside the PED,
      SRH, type 1 CNV, polyps, and HPED. There were no significant differences between
      the two OCT devices in the scores for the RPE line, retinal morphology, or type 2
      CNV and/or fibrin. CONCLUSION: HP-OCT visualizes morphologies beneath the RPE
      better than SD-OCT, and is equivalent to SD-OCT for visualizing morphologies
      above the RPE.

PMID- 24136629
TI  - "Doctor, why is my macular hole still open?".

PMID- 24136630
TI  - Letter to the editor: Relationship between mean platelet volume and retinopathy
      in patients with type 2 diabetes mellitus.

PMID- 24136631
TI  - A modified glaucoma staging system based on visual field index.
AB  - PURPOSE: To describe a modified glaucoma staging system (Modified GSS) based on
      the visual field index (VFI) and evaluate the performance of the Modified GSS
      compared with the Bascom Palmer GSS and Enhanced GSS. METHODS: A total of 549
      eyes of 549 patients were studied retrospectively. The Modified GSS was used to
      classify the glaucomatous visual field defects into stage 0 to 5 based on the
      VFI. The cutoff values for each stage were derived from VFI that were equivalent
      to mean deviations of -6, -12, -20, and -25 dB by receiver operating
      characteristic analysis. The staging performances, based on each of three GSSs,
      were compared with both the Advanced Glaucoma Intervention Study (AGIS) and
      Collaborative Initial Glaucoma Treatment Study (CIGTS) scores. RESULTS: The VFI
      cutoff values calculated for each stage were 81.5, 62.5, 42.5, and 22.5%,
      respectively. The correlation coefficient of Modified GSS was greater than that
      of Bascom Palmer GSS (p < 0.001), and correlation coefficients of Modified GSS
      and Enhanced GSS were equivalent. However, Enhanced GSS tended to classify
      moderate to severe AGIS and CIGTS scores into higher stages (p < 0.001).
      CONCLUSIONS: The Modified GSS is easy to use and accurate, and the staging
      performance is either equal or superior to existing GSSs.

PMID- 24136632
TI  - Telemonitoring for patients with COPD.

PMID- 24136633
TI  - Non-invasive versus invasive respiratory support in preterm infants at birth:
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the role of nasal continuous positive airway pressure (CPAP)
      initiated at birth for prevention of death and bronchopulmonary dysplasia in very
      preterm infants. DESIGN: Systematic review. DATA SOURCES: PubMed, Embase, the
      Cochrane Central Register of Controlled Trials, and online Pediatric Academic
      Society abstracts from the year of inception to June 2013. ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: Randomised controlled trials evaluating the effect of
      nasal CPAP compared with intubation in preterm infants born at less than 32
      weeks' gestation and presenting the outcomes of either death or bronchopulmonary
      dysplasia, or both (defined as the need for oxygen support or mechanical
      ventilation at 36 weeks corrected gestation), during hospital stay. RESULTS: Four
      randomised controlled trials (2782 participants) met the inclusion criteria, with
      1296 infants in the nasal CPAP group and 1486 in the intubation group. All the
      trials reported bronchopulmonary dysplasia independently at 36 weeks corrected
      gestation, with borderline significance in favour of the nasal CPAP group
      (relative risk 0.84, 95% confidence interval 0.68 to 1.04, risk difference -0.02,
      95% confidence interval -0.04 to 0.01). [corrected] No difference in death was
      observed (relative risk 0.88, 0.68 to 1.14, risk difference -0.02, -0.04 to 0.01,
      respectively). Pooled analysis showed a significant benefit for the combined
      outcome of death or bronchopulmonary dysplasia, or both, at 36 weeks corrected
      gestation for babies treated with nasal CPAP (relative risk 0.90 (95% confidence
      interval 0.83 to 0.98, risk difference -0.04 (95% confidence interval -0.08 to 
      0.00), NNT [corrected] of 25). CONCLUSION: One additional infant could survive to
      36 weeks without bronchopulmonary dysplasia for every 25 babies treated with
      nasal CPAP in the delivery room rather than being intubated.

PMID- 24136635
TI  - Challenges posed by the global crisis in the health workforce.

PMID- 24136634
TI  - Effectiveness of telemonitoring integrated into existing clinical services on
      hospital admission for exacerbation of chronic obstructive pulmonary disease:
      researcher blind, multicentre, randomised controlled trial.
AB  - OBJECTIVE: To test the effectiveness of telemonitoring integrated into existing
      clinical services such that intervention and control groups have access to the
      same clinical care. DESIGN: Researcher blind, multicentre, randomised controlled
      trial. SETTING: UK primary care (Lothian, Scotland). PARTICIPANTS: Adults with at
      least one admission for chronic obstructive pulmonary disease (COPD) in the year
      before randomisation. We excluded people who had other significant lung disease,
      who were unable to provide informed consent or complete the study, or who had
      other significant social or clinical problems. INTERVENTIONS: Participants were
      recruited between 21 May 2009 and 28 March 2011, and centrally randomised to
      receive telemonitoring or conventional self monitoring. Using a touch screen,
      telemonitoring participants recorded a daily questionnaire about symptoms and
      treatment use, and monitored oxygen saturation using linked instruments.
      Algorithms, based on the symptom score, generated alerts if readings were omitted
      or breached thresholds. Both groups received similar care from existing clinical
      services. MAIN OUTCOME MEASURES: The primary outcome was time to hospital
      admission due to COPD exacerbation up to one year after randomisation. Other
      outcomes included number and duration of admissions, and validated questionnaire
      assessments of health related quality of life (using St George's respiratory
      questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge,
      and adherence to treatment. Analysis was intention to treat. RESULTS: Of 256
      patients completing the study, 128 patients were randomised to telemonitoring and
      128 to usual care; baseline characteristics of each group were similar. The
      number of days to admission did not differ significantly between groups (adjusted
      hazard ratio 0.98, 95% confidence interval 0.66 to 1.44). Over one year, the mean
      number of COPD admissions was similar in both groups (telemonitoring 1.2
      admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59). Mean
      duration of COPD admissions over one year was also similar between groups (9.5
      days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88). The
      intervention had no significant effect on SGRQ scores between groups (68.2
      (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95%
      confidence interval -1.57 to 4.35)), or on other questionnaire outcomes.
      Conclusions In participants with a history of admission for exacerbations of
      COPD, telemonitoring was not effective in postponing admissions and did not
      improve quality of life. The positive effect of telemonitoring seen in previous
      trials could be due to enhancement of the underpinning clinical service rather
      than the telemonitoring communication. TRIAL REGISTRATION: ISRCTN96634935.
      FUNDING: The trial was funded by an NHS applied research programme grant from the
      Chief Scientist Office of the Scottish government (ARPG/07/03). The funder had no
      role in study design and the collection, analysis, and interpretation of data and
      the writing of the article and the decision to submit it for publication. NHS
      Lothian supported the telemonitoring service and the clinical services.

PMID- 24136636
TI  - Communication is a determinant of public health: a media campaign for tobacco
      control in India.

PMID- 24136637
TI  - MPs question potential new chair of Monitor about his work for company advising
      private health firms.

PMID- 24136638
TI  - GP confronts health minister over pressures of the job.

PMID- 24136639
TI  - Health activists attack Indian compensation formula for deaths attributed to
      clinical trials.

PMID- 24136640
TI  - Work function tuning for high-performance solution-processed organic
      photodetectors with inverted structure.
AB  - Organic photodetectors with inverted structure are fabricated by solution process
      techniques. A very thin interfacing layer of polyethyleneimine leads to a
      homogenous interface with low work function. The devices exhibit excellent
      performances, in particular in terms of low dark current density, wide range
      linearity, high detectivity, and remarkable stability in ambient air without
      encapsulation. 

PMID- 24136641
TI  - Ultrasound-guided intra-tumor injection of combined immunotherapy cures mice from
      orthotopic prostate cancer.
AB  - Intra-tumor injection of immunotherapeutic agents is often the most effective,
      likely because of concomitant modification of tumor microenvironment. We tested
      an immunotherapeutic regimen consisting of CpG oligonucleotides and of adenovirus
      mediated gene delivery of CCL16 chemokine directly into orthotopically implanted
      prostate tumors by ultrasound-guided injection, followed by systemic
      administration of an anti-IL-10R antibody. This combination treatment induced
      rapid stromal rearrangement, characterized by massive leukocyte infiltration and
      large areas of necrosis, a scenario that eventually led to complete tumor
      rejection and systemic immunity in 75 % of the treated mice. In vivo T lymphocyte
      depletion experiments demonstrated that the efficacy of CCL16/CpG/anti-IL-10R
      combination treatment relies upon CD8 T lymphocytes whereas CD4 T cells are
      dispensable. The results underlie the feasibility of echo-guided local
      immunotherapy of tumors located in visceral organs that are not easily
      accessible.

PMID- 24136642
TI  - The cross-selective titanium(III)-catalysed acyloin reaction.
AB  - A titanium(III)-catalysed intermolecular reductive coupling of ketones or imines
      with nitriles is described, which gives direct access to alpha-hydroxylated and
      alpha-aminated ketones. This coupling reaction is cross-selective and a catalytic
      version of the classical acyloin condensation. A reaction mechanism that is
      supported by first DFT calculations is discussed.

PMID- 24136643
TI  - Common solutions to resolve different dietary challenges in the ruminant
      dentition: the functionality of bovid postcanine teeth as a masticatory unit.
AB  - Plasticity of tooth shape in mammals is of great adaptive value for the efficient
      exploitation of specific feeding niches and is a crucial mechanism for ecological
      diversification. In this study, we aimed to infer chewing effectiveness from the
      functional shape of different postcanine teeth within bovids, the most diverse
      extant group of large herbivorous mammals. We consider the postcanine dentition
      as a masticatory unit and test for differences related to food biomechanical
      properties, dietary abrasiveness, and chewing dynamics. We compare functional
      properties of the postcanine tooth row among species with well-known dietary
      strategies by integrating digitalization of high-resolution occlusal surface 3D
      models of upper postcanine dentitions and quantification of the indentation index
      (D), a structural parameter representing enamel complexity. We test for
      differences in the occlusal shape among tooth positions in the postcanine
      dentition using robust, heteroscedastic tests in a one-way analysis of variance.
      Our results show three distinct patterns of enamel complexity along the tooth
      row: (1) D is more homogeneously distributed among tooth positions; (2) D
      increases gradually in the mesiodistal axis along the tooth row; and (3) D
      increases abruptly only at the transition between premolars and molars. We
      interpreted these patterns as different adaptive configurations of the postcanine
      tooth row relating to diet. Grass- and fruit-eating bovids show the same abrupt
      increase in enamel complexity at the transition from premolars to molars.
      Intermediate feeding and leaf-browsing species show the same gradual, mesiodistal
      increase in complexity along the tooth row. The absolute physical dietary
      resistance (biomechanical properties plus abrasiveness) and its relation to
      mechanical constraints of the chewing stroke are the likely selective factors
      leading to convergence of enamel complexity patterns along the tooth row among
      taxa with different diets.

PMID- 24136644
TI  - Hot topics in functional neuroradiology.
AB  - Functional neuroradiology represents a relatively new and ever-growing
      subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond
      anatomy and basic tissue signal characteristics and strives to understand the
      underlying physiologic processes of central nervous system disease. The American
      Society of Functional Neuroradiology sponsors a yearly educational and scientific
      meeting, and the educational committee was asked to suggest a few cutting-edge
      functional neuroradiology techniques (hot topics). The following is a review of
      several of these topics and includes "Diffusion Tensor Imaging of the Pediatric
      Spinal Cord"; "Diffusional Kurtosis Imaging"; "From Standardization to
      Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates
      of Clinical End Points"; Resting-State Functional MR Imaging"; and "Current Use
      of Cerebrovascular Reserve Imaging."

PMID- 24136645
TI  - Multilevel assessment of atherosclerotic extent using a 40-section multidetector
      scanner after transient ischemic attack or ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The first part of this study assessed the potential of
      MDCT with a CTA examination of the aorta and the coronary, cervical, and
      intracranial vessels in the etiologic work-up of TIA or ischemic stroke compared
      with established imaging methods. The objective of the second part of this study
      was to assess the atherosclerotic extent by use of MDCT in these patients.
      MATERIALS AND METHODS: From August 2007 to August 2011, a total of 96 patients
      with ischemic stroke or TIA without an evident cardioembolic source were
      enrolled. All patients underwent MDCT. Atherosclerotic extent was classified in
      0, 1, 2, 3, and 4 atherosclerotic levels according to the number of arterial
      territories (aortic arch, coronary, cervical, intracranial) affected by
      atherosclerosis defined as >= 50% cervical, intracranial, or coronary stenosis or
      >= 4-mm aortic arch plaque. RESULTS: There were 91 patients who had an
      interpretable MDCT. Mean age was 67.4 years (+/- 11 years), and 75 patients
      (83.3%) were men. The prevalence of 0, 1, 2, 3, and 4 atherosclerotic levels was
      48.3%, 35.2%, 12.1%, 4.4%, and 0%, respectively. Aortic arch atheroma was found
      in 47.6% of patients with 1 atherosclerotic level. The combination of aortic arch
      atheroma and cervical stenosis was found in 63.6% of patients with >= 2
      atherosclerotic levels. Patients with >= 2 atherosclerotic levels were older than
      patients with < 2 atherosclerotic levels (P = .04) in univariate analysis.
      CONCLUSIONS: MDCT might be useful to assess the extent of atherosclerosis. It
      could help to screen for high-risk patients who could benefit from a more
      aggressive preventive strategy.

PMID- 24136646
TI  - Acute bleeding in the head and neck: angiographic findings and endovascular
      management.
AB  - BACKGROUND AND PURPOSE: Life-threatening bleeding in the head and neck requires
      urgent management. This study evaluated the angiographic findings related to head
      and neck bleeding and presents endovascular management techniques. MATERIAL AND
      METHODS: Sixty-one consecutive patients who presented with acute bleeding in the
      head and neck areas and subsequently underwent endovascular therapy between
      January 2002 and October 2012 were included in our study. We evaluated the
      angiographic findings, techniques, and results of endovascular management.
      RESULTS: Contrast leakage (n = 10), pseudoaneurysm (n = 20), or both (n = 10)
      were the most common life-threatening angiographic findings (66%) and were the
      foci of immediate embolization or endoluminal vessel reconstruction. Seventeen
      patients (28%) had hypervascular staining of the tumor or mucosa, and 4 patients
      (6%) did not have any abnormal findings. The acute bleeding was successfully
      controlled by endovascular management according to the bleeding foci. Carotid
      arterial lesions, so-called "carotid blowout," required reconstructive or
      deconstructive therapy. Bleeding of the external carotid artery required specific
      branch embolization by a combination of various embolic materials. No procedure
      related complications occurred except in 1 patient who experienced acute
      infarction caused by thromboemboli from the covered stent. Seventeen patients
      (28%) were retreated due to rebleeding after the mean 20-month follow-up.
      CONCLUSIONS: Contrast leakage or a pseudoaneurysm or both seen on angiography are
      active bleeding foci and targets for therapy in patients with acute bleeding in
      the head and neck area. Despite different bleeding-control strategies according
      to vessel involvement, endovascular treatment is safe and effective for
      controlling hemorrhage.

PMID- 24136647
TI  - Pretreatment ADC histogram analysis is a predictive imaging biomarker for
      bevacizumab treatment but not chemotherapy in recurrent glioblastoma.
AB  - BACKGROUND AND PURPOSE: Pre-treatment ADC characteristics have been shown to
      predict response to bevacizumab in recurrent glioblastoma multiforme. However, no
      studies have examined whether ADC characteristics are specific to this particular
      treatment. The purpose of the current study was to determine whether ADC
      histogram analysis is a bevacizumab-specific or treatment-independent biomarker
      of treatment response in recurrent glioblastoma multiforme. MATERIALS AND
      METHODS: Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent
      glioblastoma multiformes never exposed to bevacizumab were included in this
      study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging
      examinations performed at the time of recurrence, immediately before commencement
      of treatment for recurrence, were extracted and the resulting histogram was
      fitted to a mixed model with a double Gaussian distribution. Mean ADC in the
      lower Gaussian curve was used as the primary biomarker of interest. The Cox
      proportional hazards model and log-rank tests were used for survival analysis.
      RESULTS: Cox multivariate regression analysis accounting for the interaction
      between bevacizumab- and non-bevacizumab-treated patients suggested that the
      ability of the lower Gaussian curve to predict survival is dependent on treatment
      (progression-free survival, P = .045; overall survival, P = .003). Patients with
      bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower
      Gaussian curve > 1.2 MUm(2)/ms had a significantly longer progression-free
      survival and overall survival compared with bevacizumab-treated patients with a
      lower Gaussian curve < 1.2 MUm(2)/ms. No differences in progression-free survival
      or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab
      treated patients with a mean lower Gaussian curve > 1.2 MUm(2)/ms had a
      significantly longer progression-free survival and overall survival compared with
      chemotherapy-treated patients. CONCLUSIONS: The mean lower Gaussian curve from
      ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated,
      not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with
      recurrent glioblastoma multiforme with a mean lower Gaussian curve > 1.2
      MUm(2)/ms have a survival advantage when treated with bevacizumab.

PMID- 24136648
TI  - The Independent Payment Advisory Board.

PMID- 24136649
TI  - Noninvasive diagnosis of compensated cirrhosis using an analysis of the time
      intensity curve portal vein slope gradient on contrast-enhanced ultrasonography.
AB  - PURPOSE: We measured the slope gradients (SGs) of the vascular time-intensity
      curves (TICs) of the intrahepatic vessels on contrast-enhanced ultrasonography
      (CEUS). The aim of this study was to assess the diagnostic accuracy of the SG of
      each hepatic vessel, particularly the portal vein (PV), for detecting cirrhosis
      and to compare this method with conventional modalities. METHODS: Fifty-one
      preoperative patients underwent CEUS, and the TICs were plotted. The SGs of the
      hepatic artery, PV and hepatic vein were obtained from the linear functions
      between the slope of the arrival time of the contrast agent and the peak
      enhancement time of each vessel. The transit times and levels of biochemical
      markers were also measured. The patients were divided into three groups according
      to the Metavir score: F0/1 group (n = 14), F2/3 group (n = 21) and F4 group (n =
      16). RESULTS: The PVSG significantly decreased in the F4 group (F0/1: 29.1 +/-
      2.27, F2/3: 23.1 +/- 1.86, F4: 14.7 +/- 2.13). The PVSG demonstrated high
      accuracy for diagnosing cirrhosis and was correlated with the levels of ICG-R15
      and hyaluronic acid (Spearman rank correlation; rho = -0.5691, p < 0.001 and rho
      = -0.4652, p = 0.0006). CONCLUSIONS: The PVSG has the potential to be a
      diagnostic marker for identifying patients with well-compensated cirrhosis.

PMID- 24136650
TI  - Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of
      MMP-9-expressing dendritic cells.
AB  - Cervical carcinogenesis is a consequence of persistent infection with high-risk
      human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells
      actively instruct their microenvironment to promote carcinogenesis. Here, we
      demonstrate that cervical cancer cells activate monocytes to produce their own
      CCL2 for further monocyte recruitment and reprogram their function during
      differentiation and maturation to dendritic cells (DCs). Our data show that
      cervical cancer cells suppress the induction of the chemokine receptor CCR7 in
      phenotypically mature DCs and impair their migration toward a lymph node homing
      chemokine, required to initiate adaptive immune responses. We confirmed the
      presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential
      for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and
      protumorigenic properties, is not suppressed but upregulated in immature as well
      as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer
      cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling
      pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition
      and restored CCR7-dependent migration but also blocked MMP-9 induction. This is
      the first report demonstrating the dissociation of CCR7 and MMP-9 expression in
      phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical
      cancer cells actively shape the local microenvironment. They induce the
      accumulation of myeloid cells and skew their function from immune activation to
      local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can
      counteract this functional dysbalance and should therefore be considered for
      adjuvant cervical cancer therapy.

PMID- 24136651
TI  - The thrombomodulin lectin-like domain does not change host responses to
      tuberculosis.
AB  - Tuberculosis (TB), caused by Mycobacterium (M.) tuberculosis, is a devastating
      infectious disease causing many deaths world-wide. Thrombomodulin (TM) is a
      multidomain glycoprotein expressed on all vascular endothelial cells. We here
      studied the role of the lectin-like domain of TM, responsible for a variety of
      anti-inflammatory properties of TM, during TB. We compared the extent of TM
      expression in human lung tissue of TB and control patients. The, the role of the
      lectin-like domain of TM was investigated by comparing mice lacking this domain
      (TMLeD/LeD mice) with wild-type (WT) mice during experimental lung TB induced by
      infection with M. tuberculosis via the airways. Lungs were harvested for analyses
      at two, six and 29 weeks after infection. Lung TM-expression was downregulated in
      TB patients, which was not related to changes in the amount of endothelium in
      infected lungs. TMLeD/LeD mice showed unaltered mycobacterial loads in lungs,
      liver and spleen during experimental TB. Additionally, lung histopathology and
      cytokine concentrations were largely similar in TMLeD/LeD and WT mice, while
      total leukocyte counts were increased in lungs of TMLeD/LeD mice after 29 weeks
      of infection. Mortality did not occur in either group. The lectin-like domain of
      TM does not play an important role in the host response to M. tuberculosis
      infection in mice.

PMID- 24136653
TI  - Multiple echo multi-shot diffusion sequence.
AB  - PURPOSE: To measure both transversal relaxation time (T2 ) and diffusion
      coefficients within a single scan using a multi-shot approach. Both measurements
      have drawn interest in many applications, especially in skeletal muscle studies,
      which have short T2 values. Multiple echo single-shot schemes have been proposed
      to obtain those variables simultaneously within a single scan, resulting in a
      reduction of the scanning time. However, one problem with those approaches is the
      associated long echo read-out. Consequently, the minimum achievable echo time
      tends to be long, limiting the application of these sequences to tissues with
      relatively long T2 . MATERIALS AND METHODS: To address this problem, we propose
      to extend the multi-echo sequences using a multi-shot approach, so that to allow
      shorter echo times. A multi-shot dual-echo EPI sequence with diffusion gradients
      and echo navigators was modified to include independent diffusion gradients in
      any of the two echoes. RESULTS: The multi-shot approach allows us to drastically
      reduce echo times. Results showed a good agreement for the T2 and mean
      diffusivity measurements with gold standard sequences in phantoms and in vivo
      data of calf muscles from healthy volunteers. CONCLUSION: A fast and accurate
      method is proposed to measure T2 and diffusion coefficients simultaneously,
      tested in vitro and in healthy volunteers.

PMID- 24136654
TI  - The fast filling of nano-SnO2 in CNTs by vacuum absorption: a new approach to
      realize cyclic durable anodes for lithium ion batteries.
AB  - CNTs filled with amorphous-nanocrystalline SnO2, as a unique SnO2-based
      nanocomposite structure, were synthesized by a rapid vacuum absorption followed
      by calcination. The SnO2/CNT nanocomposite anodes had a much higher Li storage
      capacity than the pristine CNTs, as well as a markedly improved cyclic
      performance (430 mA h g(-1) after 300 cycles at 0.1 A g(-1)). These superior
      electrode properties resulted from the unique feature of the amorphous
      nanocrystalline mixture of tin oxides stored in the CNT tubes of this
      nanocomposite, because this structure accommodated the stress and confined the
      volume change of Li(+) insertion/desertion in Sn. Although the nanocomposites had
      a large initial irreversible capacity loss due to SEI formation, it could be
      dramatically reduced by prelithiation treatment of the nanocomposite electrode. 

PMID- 24136652
TI  - Explosive type of moderate-resistance training induces functional,
      cardiovascular, and molecular adaptations in the elderly.
AB  - Current recommendations aimed at reducing neuromuscular and functional loss in
      aged muscle have identified muscle power as a key target for intervention trials,
      although little is known about the biological and cardiovascular systemic
      response in the elderly. This study investigated the effects of 12 weeks of low
      frequency, moderate-intensity, explosive-type resistance training (EMRT) on
      muscle strength and power in old community-dwelling people (70-75 years),
      monitoring functional performance linked to daily living activities (ADL) and
      cardiovascular response, as well as biomarkers of muscle damage, cardiovascular
      risk, and cellular stress response. The present study provides the first evidence
      that EMRT was highly effective in achieving a significant enhancement in muscular
      strength and power as well as in functional performance without causing any
      detrimental modification in cardiovascular, inflammatory, and damage parameters.
      Moreover, trained elderly subjects showed an adaptive response at both systemic
      and cellular levels by modulation of antioxidant and stress-induced markers such
      as myeloperoxidase (MPO), heat shock protein 70 (Hsp70) and 27 (Hsp27), and
      thioredoxin reductase 1 (TrxR1). 

PMID- 24136655
TI  - Preparation and degradation study of photocurable oligolactide-HA composite: a
      potential resin for stereolithography application.
AB  - The merging of stereolithography (SLA) technology to the medical field certainly
      benefits the manufacturing of parts, especially those patient-specific for the
      clinical use. This technique, however, has hardly been exploited medically due to
      a limited number of biodegradable resins for SLA processing. To extend
      application of SLA in the biomedical field, photocurable oligolactide resins were
      developed and examined for biodegradation and biocompatibility. The degradation
      was studied by monitoring the changes in weight loss, and thermal and mechanical
      properties of the photocured specimens in phosphate buffered saline (PBS) at 37
      degrees C. The results demonstrated that a resin composition played an important
      role in degradation, and the retarded degradation rate was observed for the
      highly crosslinked resin containing hydroxyapatite (HA). The less cytotoxic
      sample was also obtained from the resin with higher content of HA. These findings
      suggest the possible use of the developed photocurable oligolactide resins in SLA
      manufacturing of biodegradable implants, where their degradation behaviors can be
      designed by varying the resin composition.

PMID- 24136657
TI  - Irreproducible positive results on the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual
      test are different qualitatively from confirmed positive results.
AB  - Criteria that define low positive results on the COBAS(r) AmpliPrep/COBAS(r)
      TaqMan (CAP/CTM) HIV-1 Qual test as inconclusive have been adopted by all
      academic centres in South Africa that conduct infant HIV PCR, following previous
      investigations that showed poor specificity of these results. Retesting all
      inconclusive specimens has considerable cost implications. Therefore, it was
      attempted to characterise such inconclusive results, by comparing those that
      prove to be either negative or positive on follow-up testing. This retrospective,
      laboratory-based study found that 193 of 211 (91.5%) patients with previous
      inconclusive results (defined as reported positive by CAP/CTM but with cycle
      threshold [Ct ] values of >32 and/or fluorescence intensity [FI] values of <5)
      tested negative and only 18 (8.5%) tested positive using independently obtained
      follow-up samples after a median of 28 days. The only significant independent
      predictor of a later positive result was a higher FI value (3.326 vs. 0.495, P <
      0.0001), whereas Ct values were not predictive independently. Specimens from
      patients negative on follow-up testing differed qualitatively from specimens that
      proved to be true positives. As the lower FI values in false-positive compared to
      true-positive results probably are indicative of a non-specific signal, the
      incorporation of stringent amplification slope criteria in the assay's test
      definition file may improve correct classification and thus reduce the need for
      repeat testing of a large number of inconclusive specimens.

PMID- 24136656
TI  - High dietary folic Acid and high plasma folate in children and adults with
      phenylketonuria.
AB  - BACKGROUND: PKU patients on a strict low protein diet get most of their folic
      acid intake from protein substitute. Several protein substitutes contain high
      amounts of this vitamin. Concern has been raised about the safety of high levels
      of folic acid, especially in relation to cancer risk. METHODS: This cross
      sectional study included 34 children and 22 adults with PKU. A dietary interview
      was performed and intake of folic acid and vitamin B12 from protein substitute
      was calculated for patients compliant with their protein substitute. Intakes of
      folic acid and vitamin B12 were compared with plasma levels of folate, vitamin
      B12, and homocysteine. RESULTS: Children aged 2-9 years had the highest intake of
      folic acid according to RDI (449 %), and children aged 7-10 years had the highest
      intake of folic acid according to UL (155 %). Median plasma folate level in PKU
      children was two times the upper reference level and in PKU adults well above.
      Children between 10 and 13 years had the highest level of plasma folate. Young
      children had both a high intake and high plasma levels of vitamin B12.
      Homocysteine levels were low or in the lower part of the normal reference range
      in most patients. CONCLUSION: Children with PKU are at a particular risk of
      receiving folic acid high above RDI and many children with PKU receive doses
      above the UL. Many PKU patients have a very high level of plasma folate related
      to a very high content of folic acid in many of their protein substitutes.

PMID- 24136659
TI  - [Evaluation and contribution of OptiMAL-IT(r) test for the diagnosis of imported
      malaria in Tunisia].
AB  - The rapid test OptiMAL-IT(r) was evaluated in the diagnosis and the screening of
      imported malaria in Tunisia in comparison with microscopic techniques. This
      prospective study focused on 500 individuals recruited from September 2010 to
      September 2012 in laboratory of Parasitology of Pasteur Institute of Tunis. They
      include 192 patients with clinical manifestations suggestive of malaria and 308
      students originating from endemic areas. Microscopy of thick-and-thin blood
      smears and OptiMAL-IT(r) test were systematically performed on blood samples of
      all participants. Sixty individuals revealed infected by Plasmodium (12%).
      Positivity rates were respectively 20.3% in patients (44 cases) and 5.2% among
      asymptomatic students (16 cases) (p<0.01). The sensitivity and specificity of the
      OptiMAL-IT(r) test were respectively 88.6% and 100%. The concordance kappa was
      0.92. The sensitivity and specificity during the screening of asymptomatic
      subjects were respectively 68.8% and 98.3% with a concordance of 0.67. 

PMID- 24136658
TI  - Discovering Echinococcus granulosus thioredoxin glutathione reductase inhibitors
      through site-specific dynamic combinatorial chemistry.
AB  - In this study, we report a strategy using dynamic combinatorial chemistry for
      targeting the thioredoxin (Trx)-reductase catalytic site on Trx glutathione
      reductase (TGR), a pyridine nucleotide thiol-disulfide oxido-reductase. We chose
      Echinococcus granulosus TGR since it is a bottleneck enzyme of platyhelminth
      parasites and a validated pharmacological target. A dynamic combinatorial library
      (DCL) was constructed based on thiol-disulfide reversible exchange. We
      demonstrate the use of 5-thio-2-nitrobenzoic acid (TNB) as a non-covalent anchor
      fragment in a DCL templated by E. granulosus TGR. The heterodimer of TNB and
      bisthiazolidine (2af) was identified, upon library analysis by HPLC (IC50 = 24
      MUM). Furthermore, 14 analogs were synthetically prepared and evaluated against
      TGR. This allowed the study of a structure-activity relationship and the
      identification of a disulfide TNB-tricyclic bisthiazolidine (2aj) as the best
      enzyme inhibitor in these series, with an IC50 = 24 MUM. Thus, our results
      validate the use of DCL for targeting thiol-disulfide oxido-reductases.

PMID- 24136660
TI  - [Discontinuation of postexposure prophylaxis at the anti-rabies Center of
      Abidjan, Cote d'Ivoire].
AB  - Despite the availability of effective anti-rabies vaccine, rabies keeps affecting
      people in developing countries such as Cote d'Ivoire. The low compliance with
      Post Exposure Prophylaxis (PEP) partially explains this situation. This study was
      aiming at studying the reasons to abandon PEP. This descriptive and cross
      sectional study has taken place at the anti-rabies Center of Abidjan from October
      1st to December 2009. Data were collected in two steps: we first interviewed all
      the patients at the anti-rabies center during their first consultation, and then
      phone interviews were conducted one month later, only with exposed patients who
      abandoned their PEP. These phone calls allowed us to complete the questionnaire
      (the status of the animal and PEP discontinuation). Patients' verbal informed
      consent was obtained prior to data collection. Besides, patients were explained
      the risks they were exposed to and were advised to complete immunization. The
      results obtained revealed that, out of 220 people included in the study, 116
      (52.7%) abandoned the PEP. The compliance was lower with the protocol of five
      injections compared to that of four injections. More than half of the patients
      abandoned PEP after the first injection. In 32.8% of patients who abandoned PEP,
      the animal was dead, disappeared, was destroyed or there were no information
      about it one month after bite or scratch. Animal owners' refusal of taking in
      charge the victims (20%) and the lack of financial resources for purchasing the
      vaccine (13.6%) were the most frequent reasons to abandon PEP. To increase the
      protection of the human population against rabies and to increase the compliance
      with PEP protocols, the improvement of financial accessibility to the vaccine for
      population and the elaboration of compulsory regulations for animal owners to
      take in charge the PEP are necessary. 

PMID- 24136661
TI  - [Efficacy and tolerability of antiretroviral therapy containing tenofovir
      disoproxil fumarate-emtricitabine-efavirenz in treatment-naive patients infected
      with HIV-1 in Bobo Dioulasso (Burkina Faso, 2009-2011)].
AB  - The objective of this study was to evaluate the effectiveness and the clinical
      tolerance of a combination containing TDF/FTC/EFV in the treatment of HIV
      infection. This was a retrospective and descriptive study which included 196
      adults infected by HIV-1 and treated by a combination containing TDF/FTC/EFV
      during 29 months in the daily hospital of Bobo Dioulasso. The median duration of
      follow-up was 7 months IQR [5-14 month]. The median age was 37 years IQR [31
      45].With the initiation of treatment ARV, the median of the index of body mass
      was of 19 IQR [17-22]. The median of the lymphocytes TCD4 was 201/MUl IQR [74
      298/MUl]. During the follow-up, we reported 25 deaths (12.8%). HIV-1 RNA plasma
      viral load was undetectable in 91.9% of the patients (124/135) at six months of
      treatment. The majority of the adverse effects of the treatment were of a
      neurosensory nature (40.5%). The TDF/FTC/EFV combination showed a good
      effectiveness in the treatment of the infection with HIV-1 in the first intention
      just as a good clinical tolerance. 

PMID- 24136662
TI  - HTLV-I infection in the South West Indian Ocean islands, particularly in La
      Reunion and the Seychelles.
AB  - Data on HTLV-I are scarce in several Southwest Indian Ocean islands except for La
      Reunion and The Seychelles. The two cases of HTLV-I have been confirmed by
      Western-Blot in La Reunion, among blood donors. In Seychelles (87 400 inhabitants
      in 2012), where blood donors and some other cases are screened, HTLV-I was
      confirmed with a line immune assay in 43 persons and at least 10-20 patients are
      known to have tropical spastic paraparesia or adult T-cell lymphoma associated
      with HTLV-I. In the south-west Indian Ocean, a possibly important other issue may
      be co-infection of HTLV-1 with the Strongyloides stercoralis roundworm, which is
      endemic in all countries of the region and which can sometimes lead to severe
      symptomatic infestation. 

PMID- 24136663
TI  - [Cryptosporidiosis in Senegalese children: prevalence study and use of ELISA
      serologic diagnosis].
AB  - This is a prospective, descriptive and analytic study conducted from July 2011 to
      September 2011 at the Children National Hospital Albert Royer of Dakar and at the
      Velingara Health District. It was focused on children under 15 without reference
      to HIV status. For each child, a sample of stool was examined by the Ziehl
      Neelsen modified staining and by ELISA using the "Cryptosporidium Antigen
      Detection Microwell ELISA kit" designed to detect Cryptosporidium spp antigens.
      The aim of our study was to determine the prevalence of cryptosporidiosis in
      rural and hospital areas and to measure the performance of the ELISA kit that we
      used. Out of the 375 stool examinations performed with the Ziehl-Neelsen modified
      staining, 17 had revealed the presence of Cryptosporidium spp (4.53%). The
      prevalence in rural areas was 2% while the hospital prevalence was 7.4%, of which
      1.8% (1/57) were from urban areas and 9.8% (12/122) from suburban areas. No
      positive case was observed in children over 10 years. By ELISA, 23 positives
      cases were reported corresponding to a prevalence of 6.13% (1.8% in children
      living in urban areas, 13.1% in children from suburban areas and 3%living in
      rural areas).The correlation of this assay with the Ziehl-Neelsen modified
      staining, considered as the reference method, found that this assay had a
      sensitivity of 58.82% and a high specificity reaching 96.37%. The positive
      predictive value (PPV) was 43.4% while the negative predictive value was 98%.
      Cryptosporidiosis is a significant cause of parasitic infection among children in
      Senegal. Antigen detection of Cryptosporidium spp by ELISA in stool can be a
      complementary tool in the diagnosis of cryptosporidiosis. 

PMID- 24136665
TI  - Combined application of low-intensity pulsed ultrasound and functional electrical
      stimulation accelerates bone-tendon junction healing in a rabbit model.
AB  - The objective of this study was to elucidate the combined use of low-intensity
      pulsed ultrasound (LIPUS) and functional electrical stimulation (FES) on patella
      patellar tendon (PPT) junction healing using a partial patellectomy model in
      rabbits. LIPUS was delivered continuously starting day 3 postoperative until week
      6. FES was applied on quadriceps muscles to induce tensile force to the repaired
      PPT junction 5 days per week for 6 weeks since week 7 postoperatively. Forty
      rabbits with partial patellectomy were randomly divided into four groups:
      control, LIPUS alone, FES alone, and LIPUS + FES groups. At week 12, the PPT
      complexes were harvested for histology, radiographs, peripheral quantitative
      computed tomography, and biomechanical testing. There was better remodeling of
      newly formed bone and fibrocartilage zone in the three treatment groups compared
      with the control group. LIPUS and/or FES treatments significantly increased the
      area and bone mineral content of new bone. The failure load and ultimate strength
      of PPT complex were also highly improved in the three treatment groups. More new
      bone formed and higher tensile properties were showed in the LIPUS + FES group
      compared with the LIPUS or FES alone groups. Early LIPUS treatment and later FES
      treatment showed the additive effects of accelerating PPT junction healing.

PMID- 24136666
TI  - A novel laccase with inhibitory activity towards HIV-I reverse transcriptase and
      antiproliferative effects on tumor cells from the fermentation broth of mushroom
      Pleurotus cornucopiae.
AB  - A novel laccase with a molecular mass of 67 kDa was isolated from the
      fermentation broth of Pleurotus cornucopiae through ion exchange chromatography
      and gel filtration. The optimal pH and temperature for the laccase was pH 4.2 and
      30 degrees C, respectively. The laccase activity was remarkably inhibited by
      Fe(3+) and Hg(2+) , while it was stimulated by Cu(2+) and Pb(2+) . It inhibited
      proliferation of the hepatoma cells HepG2 and the breast cancer cells MCF-7, and
      the activity of HIV-I reverse transcriptase with IC50 values of 3.9, 7.6 and 3.7
      MUM, respectively.

PMID- 24136667
TI  - The impact of a managed care obesity intervention on clinical outcomes and costs:
      a prospective observational study.
AB  - OBJECTIVE: To evaluate the impact of a managed care obesity intervention that
      requires enrollment in an intensive medical weight management program, a
      commercial weight loss program, or a commercial pedometer-based walking program
      to maintain enhanced benefits. DESIGN AND METHODS: Prospective observational
      study involving 1,138 adults with BMI >= 32 kg m(-2) with one or more
      comorbidities or BMI >= 35 kg m(-2) enrolled in a commercial, independent
      practice association-model health maintenance organization. Body mass index,
      blood pressure, lipids, HbA1c or fasting glucose, and per-member per-month costs
      were assessed 1 year before and 1 year after program implementation. RESULTS:
      Program uptake (90%) and 1 year adherence (79%) were excellent. Enrollees in all
      three programs exhibited improved clinical outcomes and reduced rates of increase
      in direct medical costs compared to members who did not enroll in any program.
      CONCLUSIONS: A managed care obesity intervention that offered financial
      incentives for participation and a variety of programs was associated with
      excellent program uptake and adherence, improvements in cardiovascular risk
      factors, and a lower rate of increase in direct medical costs over 1 year.

PMID- 24136668
TI  - Reproductive factors and risk of premenopausal breast cancer by age at diagnosis:
      are there differences before and after age 40?
AB  - We examined the relationship between reproductive factors and risk of
      premenopausal breast cancer among women less than age 40 compared with older
      premenopausal women. We documented 374 incident cases of breast cancer diagnosed
      before age 40, and 2,533 cases diagnosed at age 40 and older among premenopausal
      women in the Nurses' Health Study cohorts. Biennial questionnaires were used to
      determine age at menarche, age at first birth, parity, breastfeeding, and other
      reproductive factors. Multivariate relative risks (RR) and 95 % confidence
      intervals (CI) were calculated using Cox proportional hazards models within age
      at diagnosis groups. Tumors in younger women were significantly more likely to be
      higher grade, larger size, and hormone receptor negative than were tumors in
      older premenopausal women (p < 0.0001). There was no significant heterogeneity
      according to age in associations between reproductive factors and risk of
      premenopausal breast cancer. First birth at age 30 or older increased breast
      cancer risk in both age groups (age <40: RR 1.10, 95 % CI 0.80-1.50; age >= 40:
      RR 1.16, 95 % CI 1.02-1.32; p-heterogeneity = 0.44). Risk of premenopausal breast
      cancer decreased with each additional year of age at menarche in both age groups
      (age <40: RR 0.93, 95 % CI 0.87-0.99; p trend = 0.02; age >= 40: RR 0.94, 95 % CI
      0.91-0.97; p trend = <0.0001). Among premenopausal parous women, breastfeeding
      was protective regardless of age at diagnosis (age <40: RR 0.84, 95 % CI 0.57
      1.22; age >= 40: RR 0.85, 95 % CI 0.72-0.99; p-heterogeneity = 0.79). In the
      largest prospective examination of reproductive risk factors and risk of breast
      cancer before and after age 40, we found that younger women were more likely to
      develop tumors with less favorable prognostic characteristics. However,
      associations between reproductive factors and risk of breast cancer were similar
      regardless of age at diagnosis of premenopausal breast cancer.

PMID- 24136669
TI  - The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or
      BRCA2 mutation.
AB  - Physicians are often approached by young women with a BRCA mutation and a recent
      history of breast cancer who wish to have a baby. They wish to know if pregnancy
      impacts upon their future risks of cancer recurrence and survival. To date, there
      is little information on the survival experience of women who carry a mutation in
      one of the BRCA genes and who become pregnant. From an international multi-center
      cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128
      case subjects who were diagnosed with breast cancer while pregnant or who became
      pregnant after a diagnosis of breast cancer. These women were age-matched to 269
      mutation carriers with breast cancer who did not become pregnant (controls).
      Subjects were followed from the date of breast cancer diagnosis until the date of
      last follow-up or death from breast cancer. The Kaplan-Meier method was used to
      estimate 15-year survival rates. The hazard ratio for survival associated with
      pregnancy was calculated using a left-truncated Cox proportional hazard model,
      adjusting for other prognostic factors. Among women who were diagnosed with
      breast cancer when pregnant or who became pregnant thereafter, the 15-year
      survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not
      become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31-1.91; p = 0.56).
      Pregnancy concurrent with or after a diagnosis of breast cancer does not appear
      to adversely affect survival among BRCA1/2 mutation carriers.

PMID- 24136670
TI  - Mortality gradient across the labour market core-periphery structure: a 13-year
      mortality follow-up study in north-eastern France.
AB  - PURPOSE: This study explores mortality related to temporary employment, about
      which very little is known to date. METHODS: In 1996, a health survey was carried
      out in the French region of Lorraine, and all members of 8,000 randomly chosen
      households were followed up for mortality over a 13-year period. Mortality of
      subjects in relation to their employment situation at baseline was analysed using
      a Cox survival regression. RESULTS: In comparison with permanent workers, for
      unemployed men, we found age and occupation-adjusted hazard ratios (HR) of 4.1
      for all-causes of death and 3.9 for non-violent causes, and for male temporary
      workers a HR of 2.2 for both all-causes and non-violent causes of death. Bad
      health, tobacco smoking and alcohol misuse explained 17 % of the excess risk for
      the unemployed and 41 % of that for temporary workers. CONCLUSION: The
      observation of large mortality inequalities across the labour market core
      periphery structure has important policy implications, particularly in terms of
      prevention focused on unhealthy behaviours among male unemployed and temporary
      workers.

PMID- 24136671
TI  - Pediatric liver transplantation for urea cycle disorders and organic acidemias:
      United Network for Organ Sharing data for 2002-2012.
AB  - Decision making concerning liver transplantation is unique for children with urea
      cycle disorders (UCDs) and organic acidemias (OAs) because of their immediate
      high priority on the waiting list, which is not related to the severity of their
      disease. There are limited national outcome data on which recommendations about
      liver transplantation for UCDs or OAs can be based. This study was a
      retrospective analysis of United Network for Organ Sharing data for liver
      recipients who underwent transplantation at an age < 18 years in 2002-2012.
      Repeat transplants were excluded. Among the pediatric liver transplants, 5.4%
      were liver-only for UCDs/OAs. The proportion of transplants for UCDs/OAs
      increased from 4.3% in 2002-2005 to 7.4% in 2010-2012 (P < 0.001). Ninety-six
      percent were deceased donor transplants, and 59% of these patients underwent
      transplantation at <2 years of age. Graft survival improved as the age at
      transplant increased (P = 0.04). Within 5 years after transplantation, the graft
      survival rate was 78% for children < 2 years old at transplant and 88% for
      children >= 2 years old at transplant (P = 0.06). Vascular thrombosis caused 44%
      of the graft losses, and 65% of these losses occurred in children < 2 years old.
      Patient survival also improved as the age at transplant increased: the 5-year
      patient survival rate was 88% for children with UCDs/OAs who were <2 years old at
      transplant and 99% for children who were >=2 years old at transplant (P = 0.006).
      At the last-follow-up (54 +/- 34.4 months), children who underwent
      transplantation for UCDs/OAs were more likely to have cognitive and motor delays
      than children who underwent transplantation for other indications. Cognitive and
      motor delays for children with UCDs/OAs were associated with metabolic disorders,
      but they were not predicted by age or weight at transplant, sex, ethnicity, liver
      graft type (split versus whole), or hospitalization at transplant in univariate
      and multivariate analyses. In conclusion, most liver transplants for UCDs/OAs
      occur in early childhood. Further research on the benefits of early
      transplantation for patients with UCDs/OAs is needed because a younger age may
      increase posttransplant morbidity.

PMID- 24136672
TI  - Thirty years of the human immunodeficiency virus epidemic and beyond.
AB  - After more than 30 years of battling a global epidemic, the prospect of
      eliminating human immunodeficiency virus (HIV) as the most challenging infectious
      disease of the modern era is within our reach. Major scientific discoveries about
      the virus responsible for this immunodeficiency disease state, including its
      pathogenesis, transmission patterns and clinical course, have led to the
      development of potent antiretroviral drugs that offer great hopes in HIV
      treatment and prevention. Although these agents and many others still in
      development and testing are capable of effectively suppressing viral replication
      and survival, the medical management of HIV infection at the individual and the
      population levels remains challenging. Timely initiation of antiretroviral drugs,
      adherence to the appropriate therapeutic regimens, effective use of these agents
      in the pre and post-exposure prophylaxis contexts, treatment of comorbid
      conditions and addressing social and psychological factors involved in the care
      of individuals continue to be important considerations. 

PMID- 24136673
TI  - Reliability assessment and correlation analysis of evaluating orthodontic
      treatment outcome in Chinese patients.
AB  - This study aimed to assess the reliability of experienced Chinese orthodontists
      in evaluating treatment outcome and to determine the correlations between three
      diagnostic information sources. Sixty-nine experienced Chinese orthodontic
      specialists each evaluated the outcome of orthodontic treatment of 108 Chinese
      patients. Three different information sources: study casts (SC), lateral
      cephalometric X-ray images (LX) and facial photographs (PH) were generated at the
      end of treatment for 108 patients selected randomly from six orthodontic
      treatment centers throughout China. Six different assessments of treatment
      outcome were made by each orthodontist using data from the three information
      sources separately and in combination. Each assessment included both ranking and
      grading for each patient. The rankings of each of the 69 judges for the 108
      patients were correlated with the rankings of each of the other judges yielding
      13 873 Spearman rs values, ranging from -0.08 to +0.85. Of these, 90% were
      greater than 0.4, showing moderate-to-high consistency among the 69
      orthodontists. In the combined evaluations, study casts were the most significant
      predictive component (R(2)=0.86, P<0.000 1), while the inclusion of lateral
      cephalometric films and facial photographs also contributed to a more
      comprehensive assessment (R(2)=0.96, P<0.000 1). Grading scores for SC+LX and
      SC+PH were highly significantly correlated with those for SC+LX+PH
      (r(SC+LX)vs.(SC+LX+PH)=0.96, r(SC+PH)vs.(SC+LX+PH)=0.97), showing that either
      SC+LX or SC+PH is an excellent substitute for all three combined assessment. 

PMID- 24136674
TI  - Role of sortase in Streptococcus mutans under the effect of nicotine.
AB  - Streptococcus mutans is a common Gram-positive bacterium and plays a significant
      role in dental caries. Tobacco and/or nicotine have documented effects on S.
      mutans growth and colonization. Sortase A is used by many Gram-positive bacteria,
      including S. mutans, to facilitate the insertion of certain cell surface
      proteins, containing an LPXTGX motif such as antigen I/II. This study examined
      the effect of nicotine on the function of sortase A to control the physiology and
      growth of S. mutans using wild-type S. mutans NG8, and its isogenic sortase
      defective and -complemented strains. Briefly, the strains were treated with
      increasing amounts of nicotine in planktonic growth, biofilm metabolism, and
      sucrose-induced and saliva-induced antigen I/II-dependent biofilm formation
      assays. The strains exhibited no significant differences with different
      concentrations of nicotine in planktonic growth assays. However, they had
      significantly increased (P<=0.05) biofilm metabolic activity (2- to 3-fold
      increase) as the concentration of nicotine increased. Furthermore, the sortase
      defective strain was more sensitive metabolically to nicotine than the wild-type
      or sortase-complemented strains. All strains had significantly increased sucrose
      induced biofilm formation (2- to 3-fold increase) as a result of increasing
      concentrations of nicotine. However, the sortase-defective strain was not able to
      make as much sucrose- and saliva-induced biofilm as the wild-type NG8 did with
      increasing nicotine concentrations. These results indicated that nicotine
      increased metabolic activity and sucrose-induced biofilm formation. The saliva
      induced biofilm formation assay and qPCR data suggested that antigen I/II was
      upregulated with nicotine but biofilm was not able to be formed as much as wild
      type NG8 without functional sortase A. 

PMID- 24136676
TI  - Massive fibrous epulis-a case report of a 10-year-old lesion.
AB  - The fibrous epulis, a common tumor-like lesion of the gingiva, appears in the
      interdental papilla as a result of local irritation. Lesions are asymptomatic and
      have a variable growth rate. A 75-year-old woman was referred for the evaluation
      of a large painless gingival mass. It had started 10 years back and has been
      increasing in size the last year. No bone involvement was noted. The tumor was
      totally removed by excision with surgical scalpel under local anesthesia without
      teeth extraction. The microscopic findings were suggestive of a fibrous epulis.
      Differential diagnosis, clinical considerations and factors to prevent recurrence
      are discussed. 

PMID- 24136675
TI  - Tooth wear against ceramic crowns in posterior region: a systematic literature
      review.
AB  - The objective of this systematic review was to assess tooth wear against ceramic
      crowns in posterior region in vitro and in vivo. An electronic PubMed search was
      conducted to identify studies on tooth wear against ceramic crowns in posterior
      region. The selected studies were analyzed in regard to type of crowns, natural
      antagonist, measuring protocol and outcome. From a yield of 1 000 titles, 43
      articles were selected for full-text analysis; finally, no in vitro and only five
      in vivo studies met the inclusion criteria. As there is heterogeneity in design,
      used measuring method, ceramics and analysis-form, a meta-analysis was not
      possible. Results of these studies are very controversial which makes a
      scientifically valid comparison impossible. This review indicated that some all
      ceramic crowns are as wear friendly as metal-ceramic crowns. Up to now, it has
      been impossible to associate tooth wear with any specific causal agent. The role
      of ceramic surface treatment that might be responsible for the changing in rate
      of tooth wear seems undetermined as yet through clinical trials. The literature
      reveals that studies on this topic are subject to a substantial amount of bias.
      Therefore, additional clinical studies, properly designed to diminish bias, are
      warranted.

PMID- 24136677
TI  - Long-term follow-up of standard microdiscectomy versus minimal access surgery for
      lumbar disc herniations.
AB  - BACKGROUND: Surgery of lumbar disc herniations is one of the most common
      neurosurgical procedures. New surgical approaches and techniques are constantly
      evolving. We present our long-term follow-up results comparing standard open
      microdiscectomy (SOMD) and minimal access microdiscectomy (MAMD) for single-level
      lumbar disc herniations. METHODS: Patients were randomized in two groups
      receiving either MAMD or SOMD. Physical and mental health and pain relief were
      assessed (ODI, SF-36 questionnaire, VAS leg and back pain). In addition, all
      patients received MR imaging for morphological evaluation of postoperative
      peridural scar tissue formation. RESULTS: Of the 60 initial patients (SOMD: 30
      pts, MAMD: 30 pts), 38 were available for long-term follow-up. Mean follow-up
      time was 33 months. Long-term follow-up revealed significant postoperative pain
      relief in both groups. Good to excellent results concerning physical and mental
      health and pain relief were achieved in both groups. Significantly less peridural
      scar tissue formation was observed in the MAMD patients, but without clinical
      impact. CONCLUSION: MAMD is a feasible alternative to the standard open approach.
      Both groups show significant and long-lasting pain relief and good to excellent
      results regarding health-related quality of life. Congruent to our short-term
      results, we observed slightly but not statistically significant better clinical
      results in the MAMD group when compared to the SOMD group.

PMID- 24136678
TI  - Anatomical variants of the basal vein of Rosenthal: prevalence in idiopathic
      subarachnoid hemorrhage.
AB  - BACKGROUND: Spontaneous, non traumatic subarachnoid hemorrhage (SAH) is a
      significant clinical problem that occurs most commonly as a result of aneurysm
      rupture. In approximately 15 % of cases, nor aneurysm or other vascular
      malformation can be identified by cerebral angiography as origin of the
      hemorrhage, and these are commonly defined as idiopathic SAH (ISAH). Because of
      the negative angiography, limited extension of the bleeding with prevalent
      prepontine pattern and the benign prognosis, the venous causes has been preferred
      rather than the arterial ones. In the literature recent studies have suggested a
      possible contribution by primitive variants of Basal vein of Rosenthal (BVR) in
      its the pathogenesis of ISAH, commonly grouped according Watanabe classification
      (type A, B and C). In this paper we evaluated the prevalence of anatomical
      variants of BVR in ISAH. METHODS: Venous drainage at angiography was
      retrospectively analyzed in 40 patients with ISAH and in 40 with unruptured
      aneurysms as controls. RESULTS AND CONCLUSIONS: Previous studies displayed a
      significant prevalence of BVR type C variants in ISAH. Conversely in our study we
      recognized variant B as prevalent, in which the BVR bifurcates to drain
      anteriorly into the uncal vein and posteriorly into the Galenic system. Similarly
      to variant C (in which the BVR drains via perimesencephalic "bridging" veins into
      cavernous, sphenoparietal, petrosal sinus or directly into transverse sinus) also
      variant B might be subjected to those stress mechanisms and intrinsic system
      'fragility' and for reasons yet to determine, sets off a consequent hemorrhage
      with clinical and radiological features typical of ISAH.

PMID- 24136679
TI  - Usefulness of minimum clinically important difference for assessing patients with
      subaxial degenerative cervical spine disease: statistical versus substantial
      clinical benefit.
AB  - BACKGROUND: The measurement of the therapeutic outcome of cervical spine
      surgeries commonly relies on four main patient reported outcomes (PROs): Neck
      Disability Index (NDI), Visual Analog Scale (VAS) for pain, and Short Form-36 (SF
      36) Physical (PCS) and Mental (MCS) Component Summary. However, the clinical
      impact of such scores and how they could effectively measure therapeutic efficacy
      remains unclear. In this context, the concept of minimum clinically important
      difference (MCID) is developing into the standard by which to evaluate
      treatments, patient satisfaction and cost-effectiveness. METHODS: Eighty-eight
      consecutive patients undergoing surgery for subaxial degenerative cervical spine
      disease were selected from a prospective blinded database. PROs (NDI, PCS, MCS
      and VAS) were collected preoperatively, and together with blinded Surgeon Ratings
      (SR) at 3 months and 6 months post-surgery. Four anchor-based approaches were
      used to calculate different MCIDs. Three anchors (VAS, HTI (Health Transition
      Item of the SF-36) and SR) were used to evaluate surgery outcome. The best
      clinically and statistically relevant MCID was chosen. RESULTS: On average, all
      patients presented with a statistically significant improvement (p < 0.001)
      postoperatively for NDI (27.42 to 19.42), PCS (33.02 to 42.03), MCS (44 to 50.74)
      and VAS (2.85 to 1.93). The four MCID anchor-based approaches yielded a range of
      values for each PRO: 2.23-16.59 for PCS, 0.11-16.27 for MCS and 2.72-12.08 for
      NDI. When compared to the VAS and HTI anchors, the area under the ROC curve was
      greater for SR. This finding suggests that SR may be a more reliable anchor for
      MCID calculation. CONCLUSION: The MDC (minimum detectable change) approach
      together with the SR anchor appears to be the most appropriate MCID method. It
      offers the greatest area under the ROC curve (threshold above the 95 % CI), and
      the choice of the anchor did not significantly affect this result. MCID values
      for this dataset were 5.6 for PCS, 5.12 for MCS and 2.41 for NDI.

PMID- 24136680
TI  - Magnetic microstructure of rolled-up single-layer ferromagnetic nanomembranes.
AB  - The magnetic microstructure of rolled-up magnetic nanomembranes is revealed both
      theoretically and experimentally. Two types of nanomembranes are considered, one
      with a non-magnetic spacer layer and the other without. Experimentally, by using
      different materials and tuning the dimensions of the rolled-up nanomembranes,
      domain patterns consisting of spiral-like and azimuthally magnetized domains are
      observed, which are in qualitative agreement with the theoretical predictions. 

PMID- 24136681
TI  - Trampling impacts on thermotolerant vegetation of geothermal areas in New
      Zealand.
AB  - Geothermal features such as geysers, mud pools, sinter terraces, fumaroles, hot
      springs, and steaming ground are natural attractions often visited by tourists.
      Visitation rates for such areas in the Taupo Volcanic Zone of New Zealand are in
      the order of hundreds of thousands annually. These areas are also habitat for
      rare and specialized plant and microbial communities that live in the steam
      heated soils of unusual chemical composition. We evaluated historical and current
      trampling impacts of tourists on the thermotolerant vegetation of the Waimangu
      and Waiotapu geothermal areas near Rotorua, and compared the results to
      experimental trampling at a third site (Taheke) not used by tourists. Historical
      tourism has removed vegetation and soil from around key features, and remaining
      subsoil is compacted into an impervious pavement on which vegetation
      recolonization is unlikely in the short term. Social tracks made by tourists were
      present at both tourist sites often leading them onto hotter soils than
      constructed tracks. Vegetation height and cover were lower on and adjacent to
      social tracks than further from them. Thermotolerant vegetation showed extremely
      low resistance to experimental trampling. This confirms and extends previous
      research that also shows that thallophytes and woody shrubs, life forms that
      dominate in thermotolerant vegetation, are vulnerable to trampling damage.
      Preservation of these vulnerable ecosystems must ensure that tourist traffic is
      confined to existing tracks or boardwalks, and active restoration of impacted
      sites may be warranted. 

PMID- 24136682
TI  - KRAS mutation confers resistance to antibody-dependent cellular cytotoxicity of
      cetuximab against human colorectal cancer cells.
AB  - Cetuximab is a chimeric IgG1 monoclonal antibody (mAb) that targets the
      extracellular domain of epidermal growth factor receptor (EGFR). Oncogenic KRAS
      mutations in tumors have been shown to be a negative predictor of the response of
      colorectal cancer (CRC) to cetuximab treatment. Cetuximab exerts its therapeutic
      effects through several mechanisms including antibody-dependent cellular
      cytotoxicity (ADCC). However, the influence of KRAS mutations on cetuximab
      mediated ADCC is not fully understood. Here, we investigated cetuximab-mediated
      ADCC in two pairs of isogenic CRC cells with or without a KRAS mutation.
      Peripheral blood mononuclear cells (PBMCs) from healthy volunteers and NK92, a
      natural killer (NK) cell line that exogenously expresses FcgammaRIIIa (CD16a),
      were used as effector cells. In an ADCC assay, perforin-dependent target cell
      lysis was not affected by the KRAS mutation status. On the other hand, perforin
      independent ADCC was observed only in CRC cells with wild-type KRAS, but not in
      cells with mutant KRAS. Neutralizing experiments revealed that the Fas-Fas ligand
      (FasL) interaction was responsible for the induction of apoptosis and perforin
      independent ADCC. Furthermore, the presence of effector cells clearly enhanced
      the growth-inhibitory effect of cetuximab only in CRC cells with wild-type KRAS,
      but not in those with mutant KRAS. These findings suggest that ADCC is an
      important mode of action of cetuximab and that KRAS mutation impairs the
      therapeutic effect exerted by cetuximab-mediated ADCC.

PMID- 24136684
TI  - Copper-catalyzed ortho-halogenation of protected anilines.
AB  - A practical Cu-catalyzed direct ortho-halogenation of anilines under aerobic
      conditions has been developed. The reaction shows typically excellent mono
      substitution selectivity, high ortho-regiocontrol and large functional group
      tolerance. 

PMID- 24136683
TI  - The use of PDE-5 inhibitors in the treatment of lower urinary tract symptoms due
      to benign prostatic hyperplasia.
AB  - The relationship between lower urinary tract symptoms secondary to BPH and ED has
      recently been the subject of significant research due to the prevalence of both
      conditions concomitantly existing in older men. Many large-scale studies have
      demonstrated an association between erectile dysfunction and lower urinary tract
      symptoms. Although the mechanisms underlying the relationship between LUTS and ED
      are not fully elucidated, several theories are currently proposed in literature:
      the nitric oxide/cGMP pathway, RhoA/Rho-kinase signaling, pelvic atherosclerosis
      associated with chronic hypoxia, and autonomic adrenergic hyperactivity. The
      mechanisms by which these pathways affect the bladder, prostate, pelvic
      vasculature and spinal cord are also the subject of current research. In this
      chapter, we examine the randomized, placebo-controlled trials that have evaluated
      the use of PDE-5Is in LUTS, as well as randomized, controlled trials (RCTs)
      researching combination PDE-5Is and alpha blockers. 

PMID- 24136685
TI  - Stoma care: the market in products lets patients down.

PMID- 24136686
TI  - Recurrent venous thromboembolism: a role for ABO blood group?

PMID- 24136687
TI  - Correlation between fractional anisotropy and motor outcomes in one-year-old
      infants with periventricular brain injury.
AB  - PURPOSE: To determine whether motor outcomes of an exercise intervention
      beginning at 2 months corrected age (CA) in children with periventricular brain
      injury (PBI) are correlated with fractional anisotropy (FA) measures derived from
      diffusion tensor imaging (DTI) at 12 months CA. MATERIALS AND METHODS: DTI was
      performed in eight infants with PBI who were randomly assigned to kicking and
      treadmill stepping exercise or a no-training condition. Development was assessed
      using the Alberta Infant Motor Scale (AIMS) and the Gross Motor Function
      Classification System (GMFCS). FA values were derived from regions of interest
      (ROIs) in the middle third of the posterior limb of the internal capsule (PLIC)
      and the posterior thalamic radiation (PTR). RESULTS: Significant correlations
      were observed between motor development and FA measures. For PLIC, the
      correlation coefficients were 0.82 between FA and AIMS, and -0.92 between FA and
      GMFCS, while for PTR the corresponding correlation coefficients were 0.73 and 
      0.80, respectively. CONCLUSION: Results of this study suggest that quantitative
      evaluation of white matter tracts using DTI at 12 months CA may be useful for
      assessment of brain plasticity in children.

PMID- 24136688
TI  - Application of gene expression programming and neural networks to predict adverse
      events of radical hysterectomy in cervical cancer patients.
AB  - The aim of this article was to compare gene expression programming (GEP) method
      with three types of neural networks in the prediction of adverse events of
      radical hysterectomy in cervical cancer patients. One-hundred and seven patients
      treated by radical hysterectomy were analyzed. Each record representing a single
      patient consisted of 10 parameters. The occurrence and lack of perioperative
      complications imposed a two-class classification problem. In the simulations, GEP
      algorithm was compared to a multilayer perceptron (MLP), a radial basis function
      network neural, and a probabilistic neural network. The generalization ability of
      the models was assessed on the basis of their accuracy, the sensitivity, the
      specificity, and the area under the receiver operating characteristic curve
      (AUROC). The GEP classifier provided best results in the prediction of the
      adverse events with the accuracy of 71.96 %. Comparable but slightly worse
      outcomes were obtained using MLP, i.e., 71.87 %. For each of measured indices:
      accuracy, sensitivity, specificity, and the AUROC, the standard deviation was the
      smallest for the models generated by GEP classifier. 

PMID- 24136689
TI  - Intra-protocol repeatability and inter-protocol agreement for the analysis of
      scapulo-humeral coordination.
AB  - Multi-center clinical trials incorporating shoulder kinematics are currently
      uncommon. The absence of repeatability and limits of agreement (LoA) studies
      between different centers employing different motion analysis protocols has led
      to a lack dataset compatibility. Therefore, the aim of this work was to determine
      the repeatability and LoA between two shoulder kinematic protocols. The first one
      uses a scapula tracker (ST), the International Society of Biomechanics anatomical
      frames and an optoelectronic measurement system, and the second uses a spine
      tracker, the INAIL Shoulder and Elbow Outpatient protocol (ISEO) and an inertial
      and magnetic measurement system. First within-protocol repeatability for each
      approach was assessed on a group of 23 healthy subjects and compared with the
      literature. Then, the between-protocol agreement was evaluated. The within
      protocol repeatability was similar for the ST ([Formula: see text] = 2.35 degrees
      , [Formula: see text] = 0.97 degrees , SEM = 2.5 degrees ) and ISEO ([Formula:
      see text] = 2.24 degrees , [Formula: see text] = 0.97 degrees , SEM = 2.3 degrees
      ) protocols and comparable with data from published literature. The between
      protocol agreement analysis showed comparable scapula medio-lateral rotation
      measurements for up to 120 degrees  of flexion-extension and up to 100 degrees 
      of scapula plane ab-adduction. Scapula protraction-retraction measurements were
      in agreement for a smaller range of humeral elevation. The results of this study
      suggest comparable repeatability for the ST and ISEO protocols and between
      protocol agreement for two scapula rotations. Different thresholds for
      repeatability and LoA may be adapted to suit different clinical hypotheses.

PMID- 24136690
TI  - Making research meaningful in a world with limited resources.

PMID- 24136691
TI  - Exercise heart rate monitors for anxiety treatment in a rural primary care
      setting: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: Rural patients with anxiety often lack access to
      traditional biofeedback modalities. Exercise heart rate monitors (HRMs) are tools
      used in the fitness industry to provide athletes with feedback on heart rate and
      regulatory breathing strategies. HRMs are inexpensive, discrete, and publicly
      accessible. This randomized controlled pilot study explored whether use of HRMs
      for biofeedback during guided mindfulness, diaphragmatic breathing, and
      progressive muscle relaxation techniques could facilitate anxiety reduction as
      compared to these techniques alone. METHODS: Fifty-three rural anxiety patients
      were randomized to HRM or control groups for four weekly 20-minute, scripted
      sessions with a non-behaviorist wherein they practiced these techniques; the HRM
      group received feedback on their heart rate response. RESULTS: The HRM group had
      significantly greater improvement in state anxiety (State-Trait Anxiety
      Inventory) and self-efficacy (General Self Efficacy Scale), and a greater
      percentage of the group indicated that they "felt in control of their anxiety."
      CONCLUSIONS: This pilot study demonstrates that this novel, inexpensive, and
      accessible tool may be a useful clinical intervention for anxiety and can be
      easily incorporated by both behaviorists and non-behaviorist primary care
      clinicians into individual or group biofeedback treatment for patients with
      anxiety. This tool has additional potential for patients to use for anxiety self
      management. Further study with a larger sample and blinded design is warranted.

PMID- 24136692
TI  - Family physician satisfaction with two different academic compensation schemes.
AB  - BACKGROUND AND OBJECTIVES: A growing body of evidence suggests that comprehensive
      relative-value-based incentive plans (CRVPs) are more effective at tracking and
      improving academic productivity than other types of academic compensation schemes
      (ACSs). However, there is little literature to date exploring physician
      satisfaction with CRVPs. METHODS: Physicians in two academic family medicine
      departments in Toronto, Ontario, completed an anonymous satisfaction survey. One
      of these departments used a CRVP to compensate for non-clinical activities; the
      control group used a monthly stipend based on full-time equivalents (FTEs).
      RESULTS: When compared with controls, physicians compensated by a CRVP were more
      likely to increase their involvement in non-clinical activities, to report being
      "very satisfied" with their ACS, to feel that their ACS made them "more likely"
      to continue working in their department, and to feel that their ACS was "fair."
      CONCLUSIONS: Physicians in a family medicine department that used a CRVP felt a
      greater sense of sense of satisfaction and fairness in terms of their
      compensation for non-clinical activities. CRVP physicians also perceived an
      increased involvement in academic activities, were more likely to continue to
      work in their current department, and to feel that the compensation for non
      clinical activities was adequate.

PMID- 24136693
TI  - Adding obesity to the problem list increases the rate of providers addressing
      obesity.
AB  - BACKGROUND AND OBJECTIVES: Obesity is a common problem that increases risk of
      many other diseases, from heart disease to cancer. While counseling by a
      physician increases patient report of weight loss attempts and increased
      exercise, primary care physicians do not frequently address obesity. The
      objectives of this study were to determine how often obesity was included on the
      problem list and whether adding obesity to the problem list affected the rate at
      which it was addressed in future visits. METHODS: We conducted an initial
      assessment, followed by a randomized controlled trial of patient records at a
      family medicine residency office. The intervention was the addition of obesity to
      the problem list. The measured outcome was whether or not obesity was listed as
      an encounter diagnosis in the following 5 months. RESULTS: At baseline, 36.2% of
      obese patients had obesity on their problem list. A total of 55.5% of these
      patients had obesity addressed by a provider in the past year, compared with 5.1%
      of patients who did not have obesity on their problem list. In the 5 months
      following the intervention, 38 (14.7%) of the 258 patients in the intervention
      group had obesity addressed, compared with 11 (4.6%) of the 239 patients in the
      control group. CONCLUSIONS: There is a significant relationship between the
      addition of obesity to the problem list and providers addressing obesity at
      future visits. This simple intervention could be accomplished automatically by
      the EMR and has the potential to change provider behavior.

PMID- 24136694
TI  - A multi-method intervention to reduce no-shows in an urban residency clinic.
AB  - BACKGROUND AND OBJECTIVES: Missed appointments can create financial, capacity,
      and continuity issues in primary care. An urban family medicine residency
      teaching clinic with a large culturally diverse population of low-income patients
      struggled for decades with a persistent no-show rate of 15%--17% despite multiple
      attempts to remind patients or otherwise address the problem. This study sought
      to measure the effects of a multi-method approach to decreasing the overall
      clinic no-show rate over time. METHODS: A team of clinicians and staff undertook
      a systematic review of the literature to identify an approach to decreasing the
      number of no-show appointments while maintaining a commitment to the population
      and quality of care. The team implemented a three-stage process: an interview
      with the cohort of patients with the highest number of repeated no-show
      appointments, a double booking process for patients with a history of frequent
      missed appointments, and a change in the entire schedule to a modified advanced
      access schedule. RESULTS: A cohort of 141 patients (2% of the practice
      population) accounted for almost 17% of the total missed appointments. The cohort
      differed from the overall clinic, being largely African American women on
      Medicaid with a large burden of medical comorbidities and a high prevalence of
      mental health issues. After the intervention, the rate of no-show appointments in
      the cohort fell from 33.3% to 17.7%, and the overall clinic rate fell from 10% to
      7%; this decrease persisted for the 33-month observation period after the
      intervention and has been maintained to this date. The largest improvement in
      appointment keeping came after a modified advanced access schedule was
      implemented clinic-wide. CONCLUSIONS: Indentifying a large at-risk population for
      no-shows and using a multi-method approach to addressing the issue can show
      persistent improvement and could be used in other residency training and
      community clinic settings.

PMID- 24136695
TI  - Entry of US medical school graduates into family medicine residencies: 2012-
      2013.
AB  - BACKGROUND: Analyzing the US medical school origin of family medicine residents
      highlights schools, states, or regions that have higher entrance rates into
      family medicine. METHODS: The American Academy of Family Physicians (AAFP) 2013
      Residency Census has a 100% response rate and lists information for family
      medicine residents who entered training July 2012. MD graduates are verified
      through medical school registrars or the American Medical Association's
      Physicians Masterfile data. The American Association of Colleges of Osteopathic
      Medicine provides data on DO graduates. Three-year rolling averages of graduates
      entering family medicine are calculated for Liaison Committee of Medical
      Education (LCME)-accredited medical schools. RESULTS: In July 2012, 3,523 first
      year residents entered Accreditation Council for Graduation Medical Education
      (ACGME)-accredited family medicine residencies. Medical students from LCME
      accredited schools account for less than half of the family medicine residents
      (46%). Public MD-granting medical schools graduate almost threefold more students
      into family medicine residencies than do private schools (1,101 versus 380). The
      Mountain, West North Central, and Pacific regions of the United States have the
      highest percentage of MD graduates (13.5%, 12.3%, and 11.4%, respectively)
      entering family medicine. Forty-five percent of MD medical students enter a
      family medicine residency in the state in which they attended medical school.
      CONCLUSIONS: LCME-accredited medical schools with lower percentages of graduates
      entering family medicine should examine the economic, environmental, and academic
      factors that may be causing low numbers of their students graduating and entering
      family medicine residencies.

PMID- 24136696
TI  - Results of the 2013 National Resident Matching Program: family medicine.
AB  - BACKGROUND: The percentage of US seniors who chose primary care careers remains
      well below the nation's future workforce needs. Entrants into family medicine
      residency programs, along with their colleagues entering other primary care
      designated residencies, will compose the primary care workforce of the future.
      METHODS: Data in this article are collected from the 2013 National Resident
      Matching Program (NRMP) Main Residency Match and the 2013 American Academy of
      Family Physicians (AAFP) Medical Education Residency Census. The information
      provided includes the number of applicants to graduate medical education programs
      for the 2013--2014 academic year, specialty choice, and trends in specialty
      selection. RESULTS: Family medicine residency programs experienced a modest
      increase in both the overall fill rate as well as the number of positions filled
      with US seniors through the NRMP in 2013 in comparison to 2012. Other primary
      care fields, primary care internal medicine positions, pediatrics-primary care,
      and internal medicine-pediatrics programs also experienced modest increases in
      2013. The 2013 NRMP results show a small increase in medical students choosing
      primary care careers for the fourth year in a row. CONCLUSIONS: Changes in the
      NRMP Match process in 2013 make a comparison to prior years' Match results
      difficult. Medical school admission changes, loan repayment, and improved primary
      care reimbursement may help increase the number of students pursuing family
      medicine.

PMID- 24136697
TI  - Lessons learned in the death and birth of GME programs.

PMID- 24136698
TI  - Life, liberty, and the third of July.

PMID- 24136699
TI  - 55-word stories: a collection from the 32nd forum for behavioral science in
      family medicine.

PMID- 24136700
TI  - Not a nice way to die.

PMID- 24136701
TI  - A dream.

PMID- 24136704
TI  - Responsible and capable family physicians.

PMID- 24136705
TI  - Polymer-coated quantum dots.
AB  - Quantum Dots (QDs) are semiconductor nanocrystals with distinct photophysical
      properties finding applications in biology, biosensing, and optoelectronics.
      Polymeric coatings of QDs are used primarily to provide long-term colloidal
      stability to QDs dispersed in solutions and also as a source of additional
      functional groups used in further chemical derivatization of the nanoparticles.
      We review the coating methods, including multidentate and amphiphilic polymeric
      coatings, and grafting-to and grafting-from approaches. We highlight the most
      commonly used polymers and discuss how their chemical structure influences the
      coating properties. 

PMID- 24136708
TI  - Pharmacokinetics of anthraquinones in rat plasma after oral administration of a
      rhubarb extract.
AB  - A sensitive and specific LC-MS/MS method was developed for simultaneous
      determination of aloe-emodin, rhein, emodin, chrysophanol and physcion and their
      conjugates in rat plasma. The lower limit of quantitation of each anthraquinone
      was 0.020-0.040 um. Intra-day and inter-day accuracies were 90.1-114.3% and the
      precisions were <14.6%. The matrix effects were 104.0-113.2%. The method was
      successfully applied to a pharmacokinetic study in rats receiving a rhubarb
      extract orally. The area under the concentration-time curve (AUC0-t ) and peak
      concentration (Cmax ) of free aloe-emodin and emodin in rat plasma were much
      lower than those of rhein. The amounts of chrysophanol and physcion were too low
      to be continuously detected. After treating the plasma samples with beta
      glucuronidases, each anthraquinone was detectable throughout the experimental
      period (36 h) and showed much higher plasma concentrations and AUC0-t . The
      free/total ratios of aloe-emodin, rhein and emodin were 6.5, 49.0 and 1.7% for
      Cmax and 3.7, 32.5 and 1.1% for AUC0-t , respectively. The dose-normalized AUC0-t
      and Cmax of the total of each anthraquinone were in the same descending order:
      rhein > emodin > chrysophanol > physcion > aloe-emodin. These findings reveal
      phase II conjugates as the dominant in vivo existing forms of rhubarb
      antharquinones and warrant a further study to evaluate their contribution to the
      herbal activity.

PMID- 24136709
TI  - Identification of a highly conserved and surface exposed B-cell epitope on the
      nucleoprotein of influenza A virus.
AB  - Influenza virus still poses a major threat to human health worldwide. The
      nucleoprotein (NP) of influenza A virus plays an essential role in the viral
      replication and transcription and hence becomes a promising therapeutic target.
      NP forms a complicated conformation under native conditions and might denature
      when performing immunoassays such as western blot in the study of NP function.
      Therefore, it is useful to make an NP specific monoclonal antibody (mAb) that
      recognizes linear epitope instead of conformational epitope. In this study, a
      recombinant NP (rNP) of influenza A virus was over-expressed and used to generate
      a panel of anti-NP mAbs. These anti-NP mAbs were grouped into three classes based
      on their reactivity in Western blots. Only Class I mAb can react with linear rNP
      fragments. One of Class I mAb, 4D2, was characterized further by epitope mapping
      with a series of overlapping synthetic peptides, indicating that the 4D2 epitope
      is a surface exposed, linear epitope between amino acid residues 243 and 251.
      This epitope is highly conserved among different influenza A viruses with an
      identity of 98.4% (17,922/18,210). Western blot, co-immunoprecipitation,
      immunofluorescence, and immunohistochemistry experiments all indicated 4D2 is
      highly specific to NP of influenza A virus. The results demonstrated that 4D2 can
      be used as a research tool for functional study of NP in the replication cycle of
      influenza A virus. Further work is needed to understand the function and
      importance of this epitope.

PMID- 24136710
TI  - Aerobic capacity during cardiopulmonary exercise testing and survival with and
      without liver transplantation for patients with chronic liver disease.
AB  - Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise
      tolerance and aerobic capacity (AC). Measures of AC determined with
      cardiopulmonary exercise testing (CPET) may predict survival after liver
      transplantation (LT), but the relationship with nontransplant outcomes is
      uncertain. In patients assessed for LT, we examined the relationship of CPET AC
      parameters with the severity of liver disease, nutritional state, and survival
      with and without LT. Patients assessed for elective first LT who underwent CPET
      and an anthropometric assessment at a single center were studied. CPET-derived
      measures of AC that were evaluated included the peak oxygen consumption (VO2
      peak) and the anaerobic threshold (AT). Three hundred ninety-nine patients
      underwent CPET, and 223 underwent LT; 45% of the patients had a VO2 peak < 50% of
      the predicted value, and 31% had an AT < 9 mL/kg/minute. The VO2 peak and AT
      values correlated with the Model for End-Stage Liver Disease score, but they more
      closely correlated with serum sodium and albumin levels. The handgrip strength
      correlated strongly with the VO2 peak. Patients with impaired AC had prolonged
      hospitalization after LT, and nonsurvivors had lower AT values than survivors 1
      year after transplantation (P < 0.05); this was significant in a multivariate
      analysis. One hundred seventy-six patients did not undergo LT; the 1-year
      mortality rate was 34.6%. The AT (P < 0.05) and VO2 peak values (P < 0.001) were
      lower for nonsurvivors. In a multivariate analysis, AT was independently
      associated with nonsurvival. In conclusion, AC was markedly impaired in many
      patients with CLD. In patients who did not undergo transplantation, impaired AT
      was predictive of mortality, and in patients undergoing LT, it was related to
      postoperative hospitalization and survival. AC should be evaluated as a
      modifiable factor for improving patient survival whether or not LT is
      anticipated.

PMID- 24136711
TI  - Triggered sorting and co-assembly of genetically engineered protein microdomains
      in the cytoplasm.
AB  - Elastin-like polypeptides (ELPs) are genetically encoded protein polymers that
      reversibly phase separate in response to stimuli. They respond sharply to small
      shifts in temperature and form dense microdomains in the living eukaryotic
      cytosol. For the first time, this communication illustrates how to tune the ELP
      sequence and architecture for either co-assembly or sorting of distinct proteins
      into microdomains within a living cell. 

PMID- 24136713
TI  - Mental imagery in chronic pain: prevalence and characteristics.
AB  - BACKGROUND: Research into mental imagery has increased our understanding of a
      range of psychological problems. However, there has been little study into the
      spontaneous mental images experienced in response to chronic pain. This study
      aimed to explore the prevalence and characteristics of these pain-related mental
      images. METHODS: Four hundred ninety-one people with chronic pain who had
      attended a pain clinic were sent invites to participate and 105 people responded
      (21%). A mixed-methods approach (quantitative and qualitative) was used to
      explore the prevalence of pain-related mental imagery, differences between
      imagers and non-imagers, and the content of imagery in pain. RESULTS: In our
      sample, 36% of respondents reported having mental images of their pain, with the
      majority describing them as clear and vivid (83%), experienced daily (80.5%), and
      distressing (83%). Participants who experienced mental images reported higher
      depression scores, higher anxiety and higher pain unpleasantness. Frequency of
      imagery was associated with greater pain unpleasantness. Content analysis of the
      pain images revealed emerging themes relating to the sensory qualities of pain,
      anatomical representations, pain as a form of threat or attack, pain as an
      object, and pain as an abstract image. CONCLUSIONS: This study describes themes
      and characteristics of pain-related mental imagery and confirms that they are a
      frequent, vivid and distressing experience for many chronic pain sufferers. The
      results of this study suggest that pain-related mental imagery could provide an
      additional route for assessment and intervention. Further research should focus
      on assessment, measurement and intervention in clinical populations.

PMID- 24136714
TI  - Nonpharmacologic treatment of behavioral disorders in dementia.
AB  - OPINION STATEMENT: Dementia symptoms are often complicated by behavioral
      disorders such as repetitive verbalizations, aggressive behavior, and pacing. In
      clinical practice, the most common responses to behavioral disorders are
      pharmacologic, mostly using antipsychotic medication, or ignoring the behavior.
      However, multiple research studies support the notion that these behavioral
      disorders in dementia are related to unmet needs that can be addressed by
      nonpharmacologic interventions. Persons with dementia present multiple unmet
      needs, most commonly pain and discomfort, need of social contact and support, and
      need of stimulation that alleviates boredom. A wide range of interventions that
      address these needs has been investigated, though the rigor of the investigations
      varied greatly depending on factors related to the behavioral disorder, setting,
      and resource limitations. In practice, the avenues to address the unmet needs
      should depend on the person's abilities and preferences. Thus, nonpharmacologic
      interventions that are individually tailored to the person with dementia comprise
      a superior response to behavioral disorders and should be at the frontline of
      treatment of these disorders.

PMID- 24136715
TI  - Complex sleep apnea.
AB  - OPINION STATEMENT: Complex sleep apnea currently refers to the emergence and
      persistence of central apneas and hypopneas following the application of positive
      airway pressure therapy in patients with obstructive sleep apnea. However, this
      narrow definition is an "outcome" and does not capture the spectrum of
      pathological activation of the respiratory chemoreflex in sleep apnea. The
      International Classification of Sleep Disorders - 3rd edition recognizes the
      phenomenon of Treatment-Related Central Sleep Apnea, but the phenotype is usually
      evident prior to onset of therapy. The key polysomnographic characteristics of
      chemoreflex modulated and mediated sleep apnea are nonrapid eye movement (NREM)
      dominance of respiratory events, short (<30 seconds) or long (>60 seconds) cycle
      time with a self-similar metronomic timing, and spontaneous improvement during
      rapid eye movement (REM) sleep. Thus, the majority of chemoreflex effects go
      unrecognized due to the bias toward obstructive sleep apnea's current scoring
      criteria. Any treatment of apparently obstructive sleep apnea, including surgery
      and oral appliances, can expose chemoreflex-driven instabilities. As both sleep
      fragmentation and a narrow CO2 reserve or increased loop gain drive the disease,
      sedatives (to induce longer periods of stable NREM sleep and reduce the
      destabilizing effects of arousals in NREM sleep) and CO2-based stabilization
      approaches are logical. Adaptive ventilation reduces mean hyperventilation yet
      can induce ventilator-patient desynchrony, while enhanced expiratory rebreathing
      space (EERS, dead space during positive pressure therapy) and CO2 manipulation
      directly stabilize respiratory control by moving CO2 above the apnea threshold.
      Carbonic anhydrase inhibition can provide further adjunctive benefits. Novel
      pharmacological approaches may target mediators of carotid body hypoxic
      sensitization, such as the balance between gas neurotransmitters. In complex
      apnea patients, single mode therapy is unlikely to be successful, and the power
      of multi-modality therapy should be harnessed for optimal outcomes.

PMID- 24136716
TI  - Evaluation of photodissociation spectroscopy as a structure elucidation tool for
      isolated clusters: a case study of Ag4(+) and Au4(+).
AB  - Resolving the structure of clusters in the gas phase often requires the
      comparison of experimental data to quantum chemical calculations. Herein, we
      present the variation of a straightforward approach, in which photodissociation
      spectra of isolated clusters are compared to optical response calculations in
      order to elucidate cluster structures. Our absorption spectra were measured using
      a newly built longitudinal beam depletion spectroscopy apparatus and recorded in
      the photon energy range homega = 1.9-3.5 eV. Cluster geometries were obtained
      using the unbiased Birmingham Cluster Genetic Algorithm coupled with density
      functional theory, while the optical response was calculated in the framework of
      time-dependent density functional theory. Experiments and excited state
      calculations are in excellent agreement using long-range corrected exchange
      correlation functionals for both ground and excited state calculations. Our
      methodology indicates a contribution of Y shaped Au4(+) whereas for Ag4(+) only
      the ground state isomer has to be considered to explain the experimental
      absorption spectrum. Our extended methodology shows two nearly degenerate isomers
      of Au4(+) probably being present in the molecular beam and therefore shows
      promise for the further structure determination of pure and binary transition
      metal clusters.

PMID- 24136718
TI  - On the ideal emergency thoracotomy incision.

PMID- 24136717
TI  - Case-control study of genus-beta human papillomaviruses in plucked eyebrow hairs
      and cutaneous squamous cell carcinoma.
AB  - Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous
      cell carcinoma (SCC). We conducted a clinic-based case-control study to
      investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and
      SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV
      DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load
      was determined in a subset of specimens positive for a single HPV type.
      Associations with SCC were estimated by odds ratios (OR) and 95% confidence
      intervals (CI) adjusted for age and sex using logistic regression. Statistical
      tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls
      (73%) (p < 0.05), and the association with SCC increased with the number of HPV
      types present, (>= 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80;
      p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in
      EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04
      3.24). Additionally, when compared with the controls, the DNA prevalence in EBH
      was significantly higher among cases for 11 of the 25 genus-beta types tested,
      when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50).
      Compared to controls, the mean viral DNA load in EBH among the selected cases was
      greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely
      than controls to have HPV DNA+ EBH for single and multiple HPV types, providing
      additional support for the potential role of genus-beta HPV infections in SCC
      development.

PMID- 24136719
TI  - Factors influencing clinically significant delayed gastric emptying after
      subtotal stomach-preserving pancreatoduodenectomy.
AB  - BACKGROUND: Subtotal stomach-preserving pancreatoduodenectomy (SSPPD), in which
      the pylorus ring is resected and most of the stomach is preserved, has been
      performed recently in Japan. This study was undertaken to clarify the incidence
      of delayed gastric emptying (DGE) after SSPPD at a high-volume hospital and to
      determine the independent factors that influence the development of DGE after
      SSPPD. METHODS: Between 2002 and 2011, 201 consecutive patients underwent
      standardized SSPPD. After SSPPD, DGE (defined according to the International
      Study Group of Pancreatic Surgery) was analyzed, and associated variables were
      assessed by univariate and multivariate analyses, retrospectively. RESULTS:
      Clinically significant DGE (grades B and C) occurred in 35 (17 %) of the 201
      patients; 26 patients had other accompanying abdominal complications (secondary
      DGE), and pancreatic leakage was the sole risk factor for DGE (odds ratio 6.63,
      95 % CI 2.86-15.74; p < 0.001). Only nine (4 % of all patients) of the 35
      patients with clinically significant DGE were classified as having DGE that had
      arisen without any obvious etiology (primary DGE). CONCLUSIONS: DGE after SSPPD
      is strongly linked to the occurrence of other postoperative intra-abdominal
      complications such as pancreatic fistula. The incidence rate of primary DGE after
      SSPPD was 4 %. Although the ISGPS classification of DGE is clearly applicable,
      the grades do not explain why DGE occurs. Primary and secondary DGE should
      therefore be defined separately.

PMID- 24136720
TI  - Educational and clinical impact of Advanced Trauma Life Support (ATLS) courses: a
      systematic review.
AB  - BACKGROUND: We aimed to systematically review the literature on the educational
      impact of Advanced Trauma Life Support (ATLS) courses and their effects on death
      rates of multiple trauma patients. METHODS: All Medline, Pubmed, and the Cochrane
      Library English articles on the educational impact of ATLS courses and their
      effects on trauma mortality for the period 1966-2012 were studied. All original
      articles written in English were included. Surveys, reviews, editorials/letters,
      and other trauma courses or models different from the ATLS course were excluded.
      Articles were critically evaluated regarding study research design, statistical
      analysis, outcome, and quality and level of evidence. RESULTS: A total of 384
      articles were found in the search. Of these, 104 relevant articles were read; 23
      met the selection criteria and were critically analyzed. Ten original articles
      reported studies on the impact of ATLS on cognitive and clinical skills, six
      articles addressed the attrition of skills gained through ATLS training, and
      seven articles addressed the effects of ATLS on trauma mortality. There is level
      I evidence that ATLS significantly improves the knowledge of participants
      managing multiple trauma patients, their clinical skills, and their organization
      and priority approaches. There is level II-1 evidence that knowledge and skills
      gained through ATLS participation decline after 6 months, with a maximum decline
      after 2 years. Organization and priority skills, however, are kept for up to 8
      years following ATLS. Strong evidence showing that ATLS training reduces
      morbidity and mortality in trauma patients is still lacking. CONCLUSIONS: It is
      highly recommended that ATLS courses should be taught for all doctors who are
      involved in the management of multiple trauma patients. Future studies are
      required to properly evaluate the impact of ATLS training on trauma death rates
      and disability.

PMID- 24136722
TI  - Origin and molecular characterization of the human-infecting H6N1 influenza virus
      in Taiwan.
AB  - In June 2013, the first human H6N1 influenza virus infection was confirmed in
      Taiwan. However, the origin and molecular characterization of this virus,
      A/Taiwan/2/2013 (H6N1), have not been well studied thus far. In the present
      report, we performed phylogenetic and coalescent analyses of this virus and
      compared its molecular profile/characteristics with other closely related
      strains. Molecular characterization of H6N1 revealed that it is a typical avian
      influenza virus of low pathogenicity, which might not replicate and propagate
      well in the upper airway in mammals. Phylogenetic analysis revealed that the
      virus clusters with A/chicken/Taiwan/A2837/2013 (H6N1) in seven genes, except
      PB1. For the PB1 gene, A/Taiwan/2/2013 was clustered with a different H6N1
      lineage from A/chicken/Taiwan/ A2837/2013. Although a previous study demonstrated
      that the PB2, PA, and M genes of A/Taiwan/2/2013 might be derived from the H5N2
      viruses, coalescent analyses revealed that these H5N2 viruses were derived from
      more recent strains than that of the ancestor of A/Taiwan/2/2013. Therefore, we
      propose that A/Taiwan/2/2013 is a reassortant from different H6N1 lineages
      circulating in chickens in Taiwan. Furthermore, compared to avian isolates, a
      single P186L (H3 numbering) substitution in the hemagglutinin H6 of the human
      isolate might increase the mammalian receptor binding and, hence, this strain's
      pathogenicity in humans. Overall, human infection with this virus seems an
      accidental event and is unlikely to cause an influenza pandemic. However, its co
      circulation and potential reassortment with other influenza subtypes are still
      worthy of attention. 

PMID- 24136723
TI  - Further evidence for the association of distinct amino acid residues with in
      vitro and in vivo growth of infectious bursal disease virus.
AB  - A cell-culture-adapted reverse genetics strain of very virulent infectious bursal
      disease virus (IBDV) of chickens, designated as BD-3tcC, having four amino acid
      substitutions (Gln253His, Asp279Asn, Ala284Thr and Ser330Arg) in the capsid
      protein VP2 was tested for its genetic stability during serial passage in
      chickens and chicken embryo fibroblast (CEF) cell culture. Results of in vitro
      and in vivo experiments demonstrated that all four introduced mutations in BD
      3tcC remained stable during serial passage in CEF cell culture, but during
      passage in chickens, amino acid residues at position 253 and 284 reverted from
      histidine to glutamine and threonine to alanine, respectively. In a parallel
      experiment, the same substitutions also occurred in a conventionally attenuated
      vaccine strain D-78 on serial passage in chickens. However, no reversion or
      substitution took place at positions 279 and 330 during in vivo passage of the
      mutant virus BD-3tcC or vaccine virus D-78. The findings provide conclusive
      evidence that while IBDV requires histidine and threonine at positions 253 and
      284 for cell culture adaptation, glutamine and alanine at these positions are
      selected preferentially during in vivo replication. 

PMID- 24136724
TI  - A potential cellular host factor homologous to ZNF-136 can interact with
      truncated nonstructural protein 2 of hepatitis C virus.
AB  - The cytoplasmic portion of the NS2 protein of hepatitis C virus (HCV) fused with
      a thioredoxin (TrX)-His tag was expressed in BL21 (DE3) cells and purified using
      an Ni-NTA His resin. Using a pull-down assay, a specific protein from the cell
      lysate of HepG2 cell lines was isolated together with immobilized truncated NS2
      protein using Ni-NTA resin. Through peptide mass fingerprinting, this specific
      protein was found to be homologous to a repressor of transcription, ZNF136. 

PMID- 24136725
TI  - Infiltrative hepatocellular carcinoma on gadoxetic acid-enhanced and diffusion
      weighted MRI at 3.0T.
AB  - PURPOSE: To determine imaging features of infiltrative hepatocellular carcinoma
      (HCC) on 3T magnetic resonance imaging (MRI) including gadoxetic acid-enhanced
      and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Eighteen patients
      with infiltrative HCC underwent liver MRI that consisted of T1- and T2-weighted
      image (T2WI), gadoxetic acid-enhanced arterial, portal, 3-min late and 20-min
      hepatobiliary phase (HBP), and DWI. Two reviewers evaluated in consensus tumor
      characteristics and lesion conspicuity using a 4-point scale. The tumor-to-liver
      contrast ratio was also measured. RESULTS: Most of the tumors (n = 16, 88.9%)
      were seen as irregular permeative masses (4.0-23.0 cm, mean 10.5 cm in diameter)
      and the remaining two as poorly defined amorphous infiltration among thrombosed
      portal veins. Internal reticulation within the tumor was characteristic and was
      most frequently observed on 3-min late phase (n = 18), followed by HBP (n = 15).
      Tumor conspicuity and tumor-to-liver contrast ratio was highest with b-800 DWI,
      which was significantly higher than those of other images (P < 0.05). CONCLUSION:
      DWI provides the highest conspicuity for infiltrative HCC compared to unenhanced
      T1- and T2WI and gadoxetic acid-enhanced MRI. The gadoxetic acid-enhanced 3-min
      late image is useful in characterizing infiltrative HCC, as it clearly depicts
      internal reticulation in all tumors.

PMID- 24136726
TI  - [Improving Prevention for Older Immigrants by Providing Lifeworld-Oriented Access
      Paths].
AB  - Older migrants of both sexes are especially affected by health exposures and
      risks. Simultaneously participation rates of older migrants in preventive and
      health promoting programmes are rather low. Findings of the research project and
      the typology developed from the qualitative research data show important
      differences in preventive behaviour and the underlying living conditions,
      experiences and attitudes. These must be considered in the development of diverse
      lifeworld-oriented strategies of access. 

PMID- 24136727
TI  - Utility of real-time Taqman PCR for antemortem and postmortem diagnosis of human
      rabies.
AB  - Rabies, a fatal zoonotic viral encephalitis remains a neglected disease in India
      despite a high disease burden. Laboratory confirmation is essential, especially
      in patients with paralytic rabies who pose a diagnostic dilemma. However,
      conventional tests for diagnosis of rabies have several limitations. In the
      present study the utility of a real-time TaqMan PCR assay was evaluated for
      antemortem/postmortem diagnosis of rabies. Human clinical samples received for
      antemortem rabies diagnosis (CSF, saliva, nuchal skin biopsy, serum), and samples
      obtained postmortem from laboratory confirmed rabies in humans (brain tissue,
      CSF, serum) and animals (brain tissue) were included in the study. All CSF and
      sera were tested for rabies viral neutralizing antibodies (RVNA) by rapid
      fluorescent focus inhibition test (RFFIT) and all samples (except sera) were
      processed for detection of rabies viral RNA by real-time TaqMan PCR. All the 29
      (100%) brain tissues from confirmed cases of human and animal rabies, and 11/14
      (78.5%) CSF samples obtained postmortem from confirmed human rabies cases were
      positive by real-time TaqMan PCR. Rabies viral RNA was detected in 5/11 (45.4%)
      CSF samples, 6/10 (60%) nuchal skin biopsies, and 6/7 (85.7%) saliva samples
      received for antemortem diagnosis. Real-time TaqMan PCR alone could achieve
      antemortem rabies diagnosis in 11/13 (84.6%) cases; combined with RVNA detection
      in CSF antemortem rabies diagnosis could be achieved in all 13 (100%) cases. Real
      time TaqMan PCR should be made available widely as an adjunctive test for
      diagnosis of human rabies in high disease burden countries like India.

PMID- 24136728
TI  - Meeting report of the 19th Annual International Congress of the International
      Liver Transplantation Society (Sydney Convention and Exhibition Centre, Sydney,
      Australia, June 12-15, 2013).
AB  - The International Liver Transplantation Society held its annual meeting from June
      12 to 15 in Sydney, Australia. More than 800 registrants attended the congress,
      which opened with a conference celebrating 50 years of liver transplantation
      (LT). The program included series of featured symposia, focused topic sessions,
      and oral and poster presentations. This report is by no means all-inclusive and
      focuses on specific abstracts on key topics in LT. Similarly to previous reports,
      this one presents data in the context of the published literature and highlights
      the current direction of LT.

PMID- 24136729
TI  - Tumor-specific cytolysis caused by an E1B55K-attenuated adenovirus in
      nasopharyngeal carcinoma is augmented by cisplatin.
AB  - An E1B55K-attenuated adenovirus, dl1520, has been shown to replicate selectively
      in and lyse tumor cells. In this study, the antitumor activities of dl1520, alone
      or in combination with the chemotherapeutic agent cisplatin, were investigated in
      nasopharyngeal carcinoma (NPC) cells. The results demonstrated that dl1520
      replicated in and destroyed NPC cells, and induced apoptosis in vitro. In a nude
      mouse xenograft model, dl1520 significantly inhibited the growth of NPC cell
      xenografts, and the viral replication was associated with tumor regression.
      Importantly, the antitumor activity of dl1520 was augmented by the addition of
      cisplatin both in vitro and in vivo, showing that dl1520 and cisplatin have a
      synergistic anti-NPC effect. These data suggest that dl1520 exerts an efficient
      anti-NPC activity through oncolysis and the induction of apoptosis, which is
      enhanced synergistically by cisplatin. These findings indicate that oncolytic
      viral therapeutics using the E1B55K-attenuated adenovirus dl1520 could be
      promising in the comprehensive treatment of NPC, especially in combination with
      platinum-based chemotherapy.

PMID- 24136730
TI  - Frequency spectroscopy of irreversible electrochemical nucleation kinetics on the
      nanoscale.
AB  - An approach is developed for probing the thermodynamics and kinetics of
      irreversible electrochemical reactions on solid surfaces based on local frequency
      voltage spectroscopy. For a model Li-ion conductor surface, two regimes for bias
      controlled behavior are demonstrated and ascribed to the difference in the
      critical nucleus size. The electrostatic and electrochemical phenomena at the tip
      surface junction are analyzed. These studies suggest an experimental pathway for
      exploring local electrochemical activity in solids. 

PMID- 24136734
TI  - Topological darkness in self-assembled plasmonic metamaterials.
AB  - Self-assembled plasmonic metamaterials are fabricated from silver nanoparticles
      covered with a silica shell. These metamaterials demonstrate topological darkness
      or selective suppression of reflection connected to global properties of the
      Fresnel coefficients. The optical properties of the studied structures are in
      good agreement with effective medium theory. The results suggest a practical way
      of achieving high phase sensitivity in plasmonic metamaterials. 

PMID- 24136731
TI  - ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve
      fiber loss and increases corneal nerve fiber density.
AB  - Small nerve fiber loss and damage (SNFLD) is a frequent complication of
      sarcoidosis that is associated with autonomic dysfunction and sensory
      abnormalities, including pain syndromes that severely degrade the quality of
      life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an
      essential feature of sarcoidosis, on the peripheral and central nervous systems.
      Current therapy of sarcoidosis-associated SNFLD consists primarily of immune
      suppression and symptomatic treatment; however, this treatment is typically
      unsatisfactory. ARA 290 is a small peptide engineered to activate the innate
      repair receptor that antagonizes inflammatory processes and stimulates tissue
      repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily
      subcutaneous administration of ARA 290 in a group of patients with documented
      SNFLD significantly improves neuropathic symptoms. In addition to improved
      patient-reported symptom-based outcomes, ARA 290 administration was also
      associated with a significant increase in corneal small nerve fiber density,
      changes in cutaneous temperature sensitivity, and an increased exercise capacity
      as assessed by the 6-minute walk test. On the basis of these results and of prior
      studies, ARA 290 is a potential disease-modifying agent for treatment of
      sarcoidosis-associated SNFLD. 

PMID- 24136735
TI  - The prevalence of neutralizing antibodies against adeno-associated virus capsids
      is reduced in young Japanese individuals.
AB  - Pre-existing antibodies against adeno-associated virus (AAV), caused by natural
      AAV infections, interfere with recombinant AAV vector-mediated gene transfer. We
      studied the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5,
      8, and 9 in healthy subjects (n = 85) and hemophilia patients (n = 59) in a
      Japanese population. For healthy subjects, the prevalence of neutralizing
      antibodies against AAV serotypes 1, 2, 5, 8, and 9 was 36.5%, 35.3%, 37.6%,
      32.9%, and 36.5%, respectively, while that in hemophilia patients was 39.7%,
      28.8%, 35.6%, 32.9%, and 27.4%, respectively. There was no difference in the
      prevalence of neutralizing antibody against each AAV serotype between the healthy
      subjects and the hemophilia patients. The prevalence of neutralizing antibodies
      against all AAV serotypes increased with age in both healthy subjects and
      hemophilia patients. High titers of neutralizing antibodies against AAV2
      (>=1:224) and AAV8 (>=1:224) were more evident in older individuals (>=42 years
      old). Approximately 50% of all screened individuals were seronegative for
      neutralizing antibodies against each AAV tested, while approximately 25% of
      individuals were seropositive for each AAV serotype tested. The prevalence of
      seronegativity for all AAV serotypes was 67.0% (healthy subjects, 68.6%;
      hemophilia patients, 65.0%) and 18.6% (healthy subjects, 20.5%; hemophilia
      patients, 15.7%) in young (<42 years old) and older subjects (>=42 years old),
      respectively. The findings from this study suggested that young subjects are more
      likely to be eligible for gene therapy based on AAV vectors delivered via an
      intravascular route because of the low prevalence of antibodies to AAV capsids.

PMID- 24136736
TI  - Inter-examination precision of magnitude-based MRI for estimation of segmental
      hepatic proton density fat fraction in obese subjects.
AB  - PURPOSE: To prospectively describe magnitude-based multi-echo gradient-echo
      hepatic proton density fat fraction (PDFF) inter-examination precision at 3 Tesla
      (T). MATERIALS AND METHODS: In this prospective, Institutional Review Board
      approved, Health Insurance Portability and Accountability Act (HIPAA) compliant
      study, written informed consent was obtained from 29 subjects (body mass indexes
      > 30 kg/m2). Three 3T MRI examinations were obtained over 75-90 min. Segmental,
      lobar, and whole liver PDFF were estimated (using three, four, five, or six
      echoes) by magnitude-based multi-echo MRI in colocalized regions of interest. For
      estimate (using three, four, five, or six echoes), at each anatomic level
      (segmental, lobar, whole liver), three inter-examination precision metrics were
      computed: intra-class correlation coefficient (ICC), standard deviation (SD), and
      range. RESULTS: Magnitude-based PDFF estimates using each reconstruction method
      showed excellent inter-examination precision for each segment (ICC >= 0.992; SD
      <= 0.66%; range <= 1.24%), lobe (ICC >= 0.998; SD <= 0.34%; range <= 0.64%), and
      the whole liver (ICC = 0.999; SD <= 0.24%; range <= 0.45%). Inter-examination
      precision was unaffected by whether PDFF was estimated using three, four, five,
      or six echoes. CONCLUSION: Magnitude-based PDFF estimation shows high inter
      examination precision at segmental, lobar, and whole liver anatomic levels,
      supporting its use in clinical care or clinical trials. The results of this study
      suggest that longitudinal hepatic PDFF change greater than 1.6% is likely to
      represent signal rather than noise.

PMID- 24136737
TI  - Parametric analysis of the spatial resolution and signal-to-noise ratio in super
      resolved spatiotemporally encoded (SPEN) MRI.
AB  - PURPOSE: Spatiotemporally Encoded (SPEN) MRI is based on progressive point-by
      point refocusing of the image in the spatial rather than the k-space domain
      through the use of frequency-swept radiofrequency pulses and quadratic phase
      profiles. This technique provides high robustness against frequency-offsets
      including B0 inhomogeneities and chemical-shift (e.g., fat/water) distortions,
      and can consequently perform fMRI at challenging regions such as the
      orbitofrontal cortex and the olfactory bulb, as well as to improve imaging near
      metallic implants. This work aims to establish a comprehensive framework for the
      implementation and super-resolved reconstruction of SPEN-based imaging, and to
      accurately quantify this method's spatial-resolution and signal-to-noise ratio
      (SNR). THEORY AND METHODS: A stepwise formalism was laid-out for calculating the
      optimal experimental parameters for SPEN, followed by analytical analysis of the
      ensuing SNR and spatial-resolution versus conventional k-space encoding.
      Predictions were then confirmed using computer simulations and experimentally.
      RESULTS: Our findings show that SPEN is governed by the same fundamental signal
      processing principles as k-space encoding, leading to similar averaging
      properties, and ultimately similar spatial-resolution and SNR levels as k-space
      encoding. CONCLUSION: Presented analysis is applicable to general
      multidimensional SPEN designs and provides a unified framework for the analysis
      of future SPEN and similar approaches based on quadratic phase encoding.

PMID- 24136738
TI  - The integrative analysis of microRNA and mRNA expression in Apis mellifera
      following maze-based visual pattern learning.
AB  - The honeybee (Apis mellifera) is a social insect with strong sensory capacity and
      diverse behavioral repertoire and is recognized as a good model organism for
      studying the neurobiological basis of learning and memory. In this study, we
      analyzed the changes in microRNA (miRNA) and messenger RNA (mRNA) following maze
      based visual learning using next-generation small RNA sequencing and
      Solexa/lllumina Digital Gene Expression tag profiling (DGE). For small RNA
      sequencing, we obtained 13 367 770 and 13 132 655 clean tags from the maze and
      control groups, respectively. A total of 40 differentially expressed known miRNAs
      were detected between these two samples, and all of them were up-regulated in the
      maze group compared to the control group. For DGE, 5 681 320 and 5 939 855 clean
      tags were detected from the maze and control groups, respectively. There were a
      total of 388 differentially expressed genes between these two samples, with 45
      genes up-regulated and 343 genes down-regulated in the maze group, compared to
      the control group. Additionally, the expression levels of 10 differentially
      expressed genes were confirmed by quantitative reverse transcription polymerase
      chain reaction (qRT-PCR) and the expression trends of eight of them were
      consistent with the DGE result, although the degree of change was lower in
      amplitude. The integrative analysis of miRNA and mRNA expression showed that,
      among the 40 differentially expressed known miRNAs and 388 differentially
      expressed genes, 60 pairs of miRNA/mRNA were identified as co-expressed in our
      present study. These results suggest that both miRNA and mRNA may play a pivotal
      role in the process of learning and memory in honeybees. Our sequencing data
      provide comprehensive miRNA and gene expression information for maze-based visual
      learning, which will facilitate understanding of the molecular mechanisms of
      honeybee learning and memory.

PMID- 24136739
TI  - Pregabalin alters nociceptive behavior and expression level of P2X3 receptor in
      the spinal dorsal horn in a rat model induced by chronic compression of the
      dorsal root ganglion.
AB  - P2X3 receptors are present in the spinal dorsal horn (SDH) and play an essential
      role in the regulation of nociception and pain. Pregabalin (PGB) has been used as
      a new antiepileptic drug in the treatment of neuropathic pain. However, it is
      unclear whether PGB-induced analgesia was associated with the P2X3 receptor in
      SDH. Here, rats were randomly divided into four groups (n = 12 per group),
      including 2 sham operation groups, which was treated by normal saline (Sham + NS
      group) or PGB (Sham + PGB group), other 2 groups with chronic compression of the
      dorsal root ganglion, a normal saline-treated CCD group (CCD+NS group), and a PGB
      treated CCD group (CCD + PGB group). A rat model of neuropathic pain was used by
      compressing the right L4 and L5 dorsal root ganglia. Each group was evaluated
      using the mechanical withdrawal threshold (MWT). The mRNA and protein levels of
      the P2X3 receptor in the ipsilateral SDH were measured by RT-PCR, western blot,
      and immunofluorescence on 14 day after CCD operation. CCD rats showed the highest
      mechanical hyperalgesia and the lowest pain threshold in the four groups.
      Simultaneously, CCD rats showed higher P2X3 mRNA and protein expression in
      ipsilateral side of the SDH than the sham operation rats. However, the MWT was
      increased and expression of P2X3 mRNA and protein in the ipsilateral SDH in CCD
      rats was decreased 3 days after PGB treatment. Thus, PGB may partially reverse
      mechanical hyperalgesia in CCD rats by inhibiting P2X3 receptor expression in the
      ipsilateral SDH.

PMID- 24136740
TI  - Association between glutathione S-transferase M1 null genotype and risk of
      gallbladder cancer: a meta-analysis.
AB  - Glutathione S-transferases (GSTs) are a family of enzymes which are involved in
      the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1)
      null genotype can impair the enzyme activity of GSTs and is suspected to increase
      the susceptibility to gallbladder cancer. Previous studies investigating the
      association between GSTM1 null genotype and risk of gallbladder cancer reported
      inconsistent findings. To quantify the association between GSTM1 null genotype
      and risk of gallbladder cancer, we performed a meta-analysis of published
      studies. We searched PubMed, Embase, and Wanfang databases for all possible
      studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval
      (95% CI) to assess the association. Meta-analysis of total included studies
      showed that GSTM1 null genotype was not associated with gallbladder cancer risk
      (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed
      that there was no association between GSTM1 null genotype and risk of gallbladder
      cancer in both Caucasians and Asians. However, meta-analysis of studies with
      adjusted estimations showed that GSTM1 null genotype was associated with
      increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038).
      Thus, this meta-analysis shows that GSTM1 null genotype is likely to be
      associated with risk of gallbladder cancer. More studies with well design and
      large sample size are needed to further validate the association between GSTM1
      null genotype and gallbladder cancer.

PMID- 24136741
TI  - Inhibitory effect and mechanism of mesenchymal stem cells on liver cancer cells.
AB  - Mesenchymal stem cells (MSCs), with their capacity for self-renewal and
      differentiation into various cell types, are important seed cells for stem cell
      therapy. MSCs exhibit potent pathotropic migratory properties that make them
      attractive for use in tumor prevention and therapy. However, little is known
      about the underlying molecular mechanisms that link MSCs to the targeted tumor
      cells. This study investigated the inhibitory effect and mechanism of MSCs on
      human hepatoma HepG2 cells using co-culture and conditioned medium system and
      animal transplantation model. The HepG2 cells were co-cultured with MSCs or
      treated with conditional media derived from MSCs cultures in vitro. Results of
      methylthiazolyldiphenyl tetrazolium assay and flow cytometric assay showed that
      the proliferation and apoptosis of HepG2 cells decreased and increased,
      respectively. Reverse transcription polymerase chain reaction analysis showed
      that the expression levels of bcl-2, c-Myc, beta-catenin, and survivin were
      downregulated. The results of enzyme-linked immunosorbent assay and Western blot
      proved that MSCs secreted Dkk-1 to inhibit the expression of Wnt signaling
      pathway-related factors (bcl-2, c-Myc, beta-catenin, and survivin) in tumor
      cells, consequently inhibiting the proliferation and promoting the apoptosis of
      HepG2 cells. Animal transplantation experiment showed that tumor growth was
      significantly inhibited when HepG2 cells were co-injected with MSCs into nude
      mice. These results suggested that MSCs inhibited the growth and promoted the
      apoptosis of HepG2 cells in a dose-dependent manner. This study provided a new
      approach and experimental basis for cancer therapy. This study also proved that
      the Wnt signaling pathway may have a function in MSC-mediated tumor cell
      inhibition.

PMID- 24136742
TI  - Vitamin D receptor rs2228570 polymorphism and susceptibly to ovarian cancer: a
      meta-analysis.
AB  - The role of vitamin D receptor (VDR) rs2228570 polymorphism on the risk of
      ovarian cancer has been studied in many studies, but the relationship between VDR
      rs2228570 polymorphism and ovarian cancer is still unclear. We thus performed a
      meta-analysis of published studies to provide a comprehensive assessment of the
      association. Fourteen individual studies with a total of 10,964 subjects were
      finally included into the meta-analysis. We assessed the association by
      calculating the pooled odds ratio (OR) with 95 % confidence intervals (95 % CI).
      There was no heterogeneity among those included studies. Meta-analysis of 14
      studies showed that the VDR rs2228570 polymorphism was associated with risk of
      ovarian cancer under three main comparison models (T versus C: OR = 1.09, 95 % CI
      1.03 to 1.15, P = 0.004; TT versus CC: OR = 1.17, 95 % CI 1.04 to 1.32, P = 0.01;
      and TT/CT versus CC: OR = 1.12, 95 % CI 1.03 to 1.21, P = 0.007). Subgroup
      analysis in Caucasians further identified the obvious association. There was no
      evidence of publications bias. These data from the meta-analysis suggest that VDR
      rs2228570 polymorphism is associated with risk of ovarian cancer in Caucasians.
      More studies are warranted to assess the association between the VDR rs2228570
      polymorphism and ovarian cancer in Asians and Africans.

PMID- 24136743
TI  - Identification and validation of dysregulated metabolic pathways in metastatic
      renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (mRCC) is a devastating disease with a 5-year
      survival rate of approximately 9 % and low response to chemotherapy and
      radiotherapy. Targeted therapies have slightly improved patient survival, but are
      only effective in a small subset of patients, who eventually develop resistance.
      A better understanding of pathways contributing to tumor progression and
      metastasis will allow for the development of novel targeted therapies and
      accurate prognostic markers. We performed extensive bioinformatics coupled with
      experimental validation on proteins dysregulated in mRCC. Gene ontology analysis
      showed that many proteins are involved in oxidation reduction, metabolic
      processes, and signal transduction. Pathway analysis showed metabolic pathways
      are altered in mRCC including glycolysis and pyruvate metabolism, the citric acid
      cycle, and the pentose phosphate pathway. RT-qPCR analysis showed that genes
      involved in the citric acid cycle were downregulated in metastatic RCC while
      genes of the pentose phosphate pathway were overexpressed. Protein-protein
      interaction analysis showed that most of the 198 proteins altered in mRCC
      clustered together and many were involved in glycolysis and pyruvate metabolism.
      We identified 29 reported regions of chromosomal aberrations in metastatic
      disease that correlate with the direction of protein dysregulation in mRCC.
      Furthermore, 36 proteins dysregulated in mRCC are predicted to be targets of
      metastasis-related miRNAs. A more comprehensive understanding of the pathways
      dysregulated in metastasis can be useful for the development of new therapies and
      novel prognostic markers. Also, multileveled analyses provide a unique "snapshot"
      of the molecular "environment" in RCC with prognostic and therapeutic
      implications. 

PMID- 24136744
TI  - Positive association between lymphotoxin-alpha variation rs909253 and cancer
      risk: a meta-analysis based on 36 case-control studies.
AB  - Lymphotoxin-alpha (LTA) polymorphism rs909253 has been reported to be a risk
      factor for cancers, but some results are inconsistent. To establish a more
      conclusive association, we performed a meta-analysis of this variant with
      cancers. A systematic search was performed for informative case-control studies
      of rs909253 with cancers among literature databases, including PubMed, Web of
      Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang
      Chinese Periodical Database. After a comprehensive filtration procedure, 36
      publications involved with 35,677 participants were selected for the current meta
      analysis. Stratified factors, such as cancer type, populations, and source of
      control, were used for a better interpretation of this variant. Minimal
      heterogeneity was shown in the current meta-analysis (I (2) = 0.0%, P = 0.48).
      Our results show a significant association of rs909253 and cancer risk (odds
      ratio (OR) = 1.12, P (z) < 0.001). In the subgroup analysis, significant
      association of rs909253 was found in adenocarcinoma (OR = 1.16, P (z) < 0.001)
      and hematological malignancy (OR = 1.10, P (z) < 0.001). Our meta-analyses
      established a significant association of rs909253 with cancer risk among multiple
      populations including North Americans, Asians, and Europeans.

PMID- 24136745
TI  - Association between microRNA genetic variants and susceptibility to colorectal
      cancer in Chinese population.
AB  - MicroRNAs (miRNAs) play an important role in the pathogenesis of neoplasm. Single
      nucleotide polymorphisms (SNPs) within miRNAs can change their phenotype and
      function. We attempted to analyze the relationship between two SNP loci in miRNAs
      and colorectal cancer (CRC) in Chinese Han population. We genotyped the
      polymorphism of two common miRNA SNPs, miR-146a (rs2910164 G > C) and miR-499
      (rs3746444 T > C), in a case-control study of 276 CRC cases and 373 healthy
      controls using polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). The genotypes and allele frequencies of the two SNP loci were first
      compared between patients and controls and then further analyzed among subgroups
      of patients with different clinicopathological profiles. The rs2910164 CG
      genotype was significantly associated with a decreased risk of CRC [CG versus GG,
      odds ratio (OR) = 0.567; 95% confidence intervals (CIs) = 0.338-0.952; p =
      0.031]. No significant differences of miR-499 genotype and allele distribution
      were detected between patients and controls. Comparison between groups divided by
      clinicopathologic features showed that the polymorphism of miR-146a was
      associated with the degree of tumor differentiation (p = 0.014), and the G allele
      of rs2910164 trended to a mature differentiation (OR = 0.553; 95% CI = 0.315
      0.971; p = 0.038). MiR-146a (rs2910164 G > C) polymorphism is associated with CRC
      susceptibility and histological differentiation in Chinese Han population.

PMID- 24136746
TI  - Level of plasmacytoid dendritic cells is increased in non-small cell lung
      carcinoma.
AB  - In non-small cell lung carcinoma (NSCLC), the immune system fails to eradicate
      established tumors partly due to the induction of immune tolerance within the
      tumor microenvironment. Plasmacytoid dendritic cells (pDCs) play critical roles
      in regulating the immune system. In this study, we investigated pDCs in the
      peripheral blood of NSCLC. CD4 + CD123 + BDCA2+ pDCs were tested from peripheral
      blood mononuclear cells in 52 NSCLC patients and 52 healthy controls by flow
      cytometry. Results revealed that proportion of pDCs was significantly increased
      in cases than in controls (0.52 +/- 0.07% versus 0.21 +/- 0.02%, p < 0.001),
      whereas myeloid dendritic cells (mDCs) did not present any obvious difference
      between patients and healthy donors (0.25 +/- 0.04 % versus 0.18 +/- 0.02%, p =
      0.120). We further studied pDCs in NSCLC patients with different clinical stages.
      Data showed that cases with higher stages (III/IV) had elevated level of pDCs
      than those with lower stages (I/II) (0.65 +/- 0.09% versus 0.25 +/- 0.07%, p =
      0.006). In addition, the amount of pDCs was identified to be associated with
      squamous cell carcinoma, one of the major subtypes of NSCLC. Interestingly, we
      observed that smoking patients presented significantly elevated pDCs than those
      non-smokers (0.63 +/- 0.09% versus 0.22 +/- 0.05%, p = 0.008). These data
      suggested that pDCs may be closely involved in the pathogenesis of NSCLC and may
      predict the progression of the disease.

PMID- 24136747
TI  - Astrocyte elevated gene-1 is a novel biomarker of epithelial-mesenchymal
      transition and progression of hepatocellular carcinoma in two China regions.
AB  - Astrocyte elevated gene-1 (AEG-1) is involved in important biological processes
      including cell invasion, metastasis, and carcinogenesis. However, its clinical
      significance has remained largely unknown in hepatocellular carcinoma. Here,
      specimens from 144 patients with hepatocellular carcinomas in Beijing and
      Heilongjiang regions were investigated by immunohistochemical staining for AEG-1,
      vimentin, and E-cadherin expressions. A clinicopathological study revealed that
      AEG-1 expression level in tumor cells was significantly correlated with TNM stage
      (P = 0.001) and Edmonson grade (P < 0.0001). In addition, AEG-1, vimentin, and E
      cadherin (epithelial-mesenchymal transition (EMT) biomarker) expressions were
      correlated with each other. These findings suggest that AEG-1 may be an
      epithelial-mesenchymal transition-associated biomarker in human hepatocellular
      carcinoma and play important roles in the progression of hepatocellular
      carcinoma. In addition, the AEG-1 gene is a potential target for elimination of
      hepatocellular carcinoma in the future. 

PMID- 24136748
TI  - Variance of TNFAIP8 expression between tumor tissues and tumor-infiltrating CD4+
      and CD8+ T cells in non-small cell lung cancer.
AB  - Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) has been recently
      documented in various malignancies, but its role in non-small cell lung cancer
      (NSCLC) remains uncertain. In the current study, we investigated the level of
      TNFAIP8 in NSCLC tissues, adjacent noncancerous lung tissues, healthy lung
      tissues, CD4+ T cells, and CD8+ T cells by real-time reverse transcription PCR
      (RT-PCR) and Western blot analysis. Results revealed that the mRNA level of
      TNFAIP8 was significantly increased in cancer tissue than in healthy lung tissue
      from donors (p < 0.001). Interestingly, adjacent noncancerous lung tissues also
      showed higher mRNA level of TNFAIP8 than healthy lung tissue from donors (p <
      0.01). Similarly, protein level of TNFAIP8 was elevated in NSCLC tissues and
      adjacent noncancerous lung tissues. We further analyzed TNFAIP8 expression in
      CD4+ T cells and CD8+ T cells. Data demonstrated that both mRNA level and protein
      level were significantly decreased in tumor-infiltrating CD4+ and CD8+ T cells
      than in peripheral CD4+ and CD8+ T cells. Moreover, patients with advanced stages
      presented lower protein expression of TNFAIP8 in tumor-infiltrating CD8+ T cells
      than patients with primary stages (p < 0.05). These results provide evidence that
      TNFAIP8 plays critical roles in NSCLC and may be used as a therapeutic target for
      the disease. 

PMID- 24136749
TI  - Patent ductus venosus and acute liver failure in the neonate: consider neonatal
      hemochromatosis with liver scarring.

PMID- 24136750
TI  - 'Mirroring' the ethics of biobanking: what should we learn from the analysis of
      consent documents[corrected]?
AB  - Biobanks have been recognized as a key research infrastructure and how to
      approach ethical questions has been a topic of discussion for at least a decade
      by now. This article explores the characteristics of donors' participation in
      European biobanks as reflected in the consent documents of a selection of
      different biobanks from various European countries. The primary aim of this study
      is to understand how donors are informed about their participation in biobanking.
      Also the paper discusses what the most important thematic issues of information
      are to be given to the biobank participants and how this information should be
      presented in the consent documents. For these purposes, we analyse consent
      documents from 14 biobanks in 11 countries for six ethically relevant issues: (1)
      model of consent, (2) scope of future research, (3) access to medical data, (4)
      feedback to the participants, (5) consent withdrawal, and (6) role of research
      ethics committee. In order to compare different trends of informing donors of
      human biological material and medical data, we interpret the six analysed issues
      in the context of respect to donor's autonomy paradigm. Although the results of
      the paper reflect the heterogeneity of biobank consent document policies applied
      in different European countries, we uncovered some trends and suggested several
      examples of good practices to balance the interests of the donors with those of
      the researchers and future patients. 

PMID- 24136751
TI  - Agreement of BNP and NT-proBNP and the influence of clinical and laboratory
      variables.
AB  - OBJECTIVE: To correlate the serum levels of B type natriuretic peptide and the N
      terminal fraction of the pro-B type natriuretic peptide, as well as to analyze
      the influence of age, obesity, renal failure, left ventricle ejection fraction,
      diastolic dysfunction, and anemia on serum levels of both markers. METHODS: An
      observational study in which the agreement was compared between these markers in
      consecutive samples of 138 patients. For the correlation, Pearson's test was
      used, and p<0.05 was considered statistically significant. RESULTS: A linear
      association was observed between the B type natriuretic peptide and N-terminal
      fraction of the pro-B type natriuretic peptide (r=0.907; p<0.001). When
      evaluating the categorized measurements as normal and altered, there was good
      agreement, with 90.6% of agreement classifications (p<0.001) in which altered
      values of the N-terminal fraction of the pro-B type natriuretic peptide and
      normal values of the B type natriuretic peptide represented 8.7% of the total;
      the opposite situation represented 1% of the total. Assessment of the influence
      of the clinical and laboratorial factors on the levels of natriuretic peptides
      showed that they rise according to age, but that they fall as the ejection
      fraction increases. Patients with anemia (p<0.001) or with renal failure
      (p=0.007) had higher values of both markers. There was no association between
      obesity and the B type natriuretic peptide. CONCLUSION: There was satisfactory
      agreement between the B type natriuretic peptide and the N-terminal fraction of
      the pro-B type natriuretic peptide. Age, creatinine levels, and hemoglobin, as
      well as ventricular function, influence the serum levels of both natriuretic
      peptides.

PMID- 24136752
TI  - Evaluating compliance to a cardiac rehabilitation program in a private general
      hospital.
AB  - OBJECTIVE: Identify the primary factors that influenced the participant in our
      cardiovascular rehabilitation program towards missing their therapy sessions, and
      to correlate those factors with age, cardiovascular risk, and motivation of our
      population. METHODS: We conducted a retrospective study with 42 patients (69.15+/
      13.93 years) participating in the cardiac rehabilitation program at a general
      hospital in Sao Paulo, through the analysis of two scales applied during the
      initial evaluation: Cardiac Rehabilitation Barriers Scale and scale of the
      original provision. We used Spearman correlation to relate them to absenteeism,
      cardiovascular risk age and duration of cardiac rehabilitation. RESULTS: The
      total score of barriers was 31+/-6 and the mean score of 1.47+/-0.31. The main
      barriers subscales were related to "travel/labor dispute" and "personal
      problems/family." The percentage of absenteeism was 8.4% in the number of
      sessions that could be made in the month. The faults and cancellations were
      positively correlated with cardiovascular risk (p=0.01; r=0.4) and negatively
      with scale provision of baseline (p=0.03; r=-0.35) and age (p=0.02; r=-0.35).
      CONCLUSION: "Travel/labor dispute", "personal/ family problems", and low initial
      provision are the main factors absenteism in a cardiac rehabilitation program in
      a general hospital in Sao Paulo.

PMID- 24136753
TI  - Heart rate variability and its relationship with central and general obesity in
      obese normotensive adolescents.
AB  - OBJECTIVE: To analyze the relationship between the heart rate variability
      parameters and the indicators of central and general obesity in obese
      normotensive adolescents. METHODS: Seventyfour 13 to 18 year-old obese
      normotensive adolescents participated in this study. The indicators analyzed for
      central and general obesity were waist circumference and body mass index,
      respectively. Heart rate variability was obtained by heart rate monitoring. For
      this, the adolescents remained in a supine position for 7 minutes with controlled
      breathing. Parameters were obtained in time domain (standard deviation of all the
      RR intervals, root mean square of successive differences between the normal
      adjacent RR intervals and the percentage of adjacent intervals with more than
      50ms) and frequency domain variables (low and high frequency bands and the
      sympathovagal balance). RESULTS: After adjustments for gender, age, and
      cardiorespiratory fitness, a negative correlation between the waist circumference
      and the root mean square of successive differences between the normal adjacent RR
      intervals (beta=-1.51; standard error=0.56; p<0.05) and the percentage of
      adjacent intervals with more than 50 ms (beta=-0.96; standard error=0.34; p<0.05)
      were observed, while the body mass index showed no significant correlation with
      any heart rate variability parameter (p>0.05). CONCLUSION: Central obesity is a
      better discriminator than general obesity of autonomic cardiac dysfunction in
      obese normotensive adolescents.

PMID- 24136754
TI  - Electrophysiological characteristics of Chagas disease.
AB  - OBJECTIVE: Chagas disease has become a global problem due to changing migration
      patterns. An electrophysiological study is generally indicated for assessing
      sinus node function, conduction through the atrioventricular node and His
      Purkinje system, in addition to evaluating the mechanisms of arrhythmia. The aim
      of this study was to describe the characteristics of electrophysiological study
      findings in patients with Chagas disease. METHODS: A retrospective descriptive
      study of 115 consecutive patients with Chagas disease undergoing an
      electrophysiological study over the last three years in a tertiary hospital in
      Brazil. Baseline characteristics, electrocardiogram, echocardiogram, and 24-hour
      Holter monitoring findings were recorded and correlated with the
      electrophysiological study findings. RESULTS: The corrected sinus node recovery
      time and sinoatrial conduction time were abnormal in 6.9% and 26.1% of patients,
      respectively. Thirty-seven (32.2%) had abnormal atrioventricular conduction.
      Intraventricular conduction was abnormal in 39 (33.9%). Approximately 48% had
      induced sustained ventricular arrhythmias, most of which were monomorphic
      (83.6%). Right bundle branch block was the most common morphology (52.7%). Fifty
      one percent were associated with symptoms/hemodynamic instability, 60% required
      electrical cardioversion, and 27.3% needed overdrive suppression. The most common
      site of origin was the left ventricular inferoseptal wall (18.2%), followed by
      the left ventricular posterobasal wall (11%). Patients with an ejection
      fraction<40% had a 1.94-fold increased risk of ventricular arrhythmias compared
      to those with an ejection fraction>60% (OR: 1.94; 95%CI: 1.12-3.38; p=0.01). The
      presence of complex ventricular arrhythmias on Holter did not predict inducible
      ventricular arrhythmias. CONCLUSIONS: Chagas patients with a low ejection
      fraction have an increased risk of inducible ventricular arrhythmias. Sinus node
      dysfunction, and atrioventricular node and His-Purkinje conduction abnormalities
      occur in about one-third of patients. Complex ventricular arrhythmias on Holter
      were not associated with an increased risk of inducible ventricular arrhythmias.

PMID- 24136755
TI  - Robotic surgery in cardiology: a safe and effective procedure.
AB  - OBJECTIVE: To evaluate the short and medium-term outcomes of patients undergoing
      robotic-assisted minimally invasive cardiac surgery. METHODS: From March 2010 to
      March 2013, 21 patients underwent robotic-assisted cardiac surgery. The
      procedures performed were: mitral valve repair, mitral valve replacement,
      surgical correction of atrial fibrillation, surgical correction of atrial septal
      defect, intracardiac tumor resection, totally endoscopic coronary artery bypass
      surgery and pericardiectomy. RESULTS: The mean age was 48.39+/-18.05 years. The
      mean cardiopulmonary bypass time was 151.7+/-99.97 minutes, and the mean aortic
      cross-clamp time was 109.94+/-81.34 minutes. The mean duration of intubation was
      7.52+/-15.2 hours, and 16 (76.2%) patients were extubated in the operating room
      immediately after the procedure. The mean length of intensive care unit stay was
      1.67+/-1.46 days. There were no conversions to sternotomy. There was no in
      hospital death or deaths during the medium-term follow-up. Patients mean follow
      up time was 684+/-346 days, ranging from 28 to 1096 days. CONCLUSION: Robotic
      assisted cardiac surgery proved to be feasible, safe and effective and can be
      applied in the correction of various intra and extracardiac pathologies.

PMID- 24136756
TI  - Relevance of prehypertension as a diagnostic category in asymptomatic adults.
AB  - OBJECTIVE: To assess the association of prehypertension with metabolic,
      inflammatory and cardiovascular risk profile in asymptomatic individuals.
      METHODS: Between 2006 and 2009, 11,011 asymptomatic adults (mean age: 43 years;
      22% females), underwent a check-up protocol. They were divided into 3 groups:
      normotensive group (arterial pressure=120/80mmHg), prehypertensive group
      (arterial pressure >120/80mmHg and <140/90mmHg) and hypertensive group (arterial
      pressure>140/90mmHg or prior diagnosis of hypertension). Each group metabolic and
      cardiovascular group profile was assessed. RESULTS: The prevalence of
      normotension, prehypertension and hypertension was 27.9%, 53.9% and 18.2%,
      respectively. Prehypertensive individuals were older (mean age: 42.7 versus 40
      years; p<0.001) than normotensive patients, and had higher body mass index (mean:
      26.7kg/m2 versus 24kg/m2; p<0.001), higher plasma triglycerides levels (mean:
      139mg/dL versus 108mg/dL; p<0.001), higher LDL-choleterol levels (mean: 128mg/dL
      versus 117mg/dL; p<0.001), and lower HDL-cholesterol (mean: 46.7mg/dL versus
      52.7mg/dL; p<0.001). Prehypertensive individuals were more likely to have
      impaired fasting glucose (OR: 1.69; 95%CI: 1.39-2.04), overweight and obesity -
      body mass index >25kg/m2 (OR: 2.48; 95%CI: 2.24-2.74), hepatic steatosis: (OR:
      2.23; 95%CI: 1.97-2.53), metabolic syndrome (OR: 3.05; 95%CI: 2.67-3.49), and
      high-sensitivity C-reactive protein levels>2mg/L (OR: 1.52; 95%CI: 1.35-1.71).
      CONCLUSION: Prehypertension is associated with an increased prevalence of
      metabolic syndrome, hepatic steatosis and subclinical inflammation.

PMID- 24136757
TI  - Implementation of an institutional protocol for rational use of blood products
      and its impact on postoperative of coronary artery bypass graft surgery.
AB  - OBJECTIVE: Cardiac surgeries are sometimes followed by significant blood loss,
      and blood transfusions may be necessary. However, indiscriminant use of blood
      components can result in detrimental effects for the patient. We evaluated the
      short-term effects of implementation of a protocol for the rational use of blood
      products in the perioperative period of cardiac surgery. METHODS: Between April
      and June 2011, an institutional protocol was implemented in a private hospital
      specializing in cardiology to encourage rational use of blood products, with the
      consent and collaboration of seven cardiac surgery teams. We collected clinical
      and demographic data on the patients. The use of blood products and clinical
      outcomes were analyzed during hospital stay before and after protocol
      implementation. The protocol consisted of an institutional campaign with an
      educational intervention to surgical and anesthesiology teams; the goal was to
      tailor blood transfusion practice according to clinical goals (anemia with
      hemodynamic changes and significant ventricular dysfunction) and to make routine
      the prescription of epsilon-aminocaproic acid intraoperatively, which is
      recommended by international guidelines based on scientific evidence. RESULTS:
      After three months of protocol implementation, the use of epsilon-aminocaproic
      acid increased from 31% to 100%. A total of 67% of surgeries before protocol
      implementation required any blood transfusion, compared with 40% that required
      any blood transfusion after protocol implementation in subsequent months of the
      same year (p<0.001). There was no significant difference in clinical outcomes
      assessed before and after implementation of the protocol. CONCLUSION: The
      rational use of blood products associated with infusion of epsilon-aminocaproic
      acid has the potential to reduce the number of blood transfusions in
      perioperative of cardiac surgeries, but it can affect the risk of complications.

PMID- 24136758
TI  - Clinical and echocardiographic characteristics associated with the evolution of
      the ductus arteriosus in the neonate with birth weight lower than 1,500g.
AB  - OBJECTIVE: To identify clinical and echocardiographic parameters associated with
      the evolution of the ductus arteriosus in neonates with birth weight lower than
      1,500g. METHODS: Retrospective study of 119 neonates in which clinical parameters
      (Prenatal: maternal age, risk of infection and chorioamnionitis, use of
      corticosteroid, mode of delivery and gestational age. Perinatal: weight, Apgar
      score, gender and birth weight/gestational age classification; Postnatal: use of
      surfactant, sepsis, fluid intake, heart murmur, heart rate, precordial movement
      and pulses, use of diuretics, oxygenation index, desaturation/apnea, ventilatory
      support, food intolerance, chest radiography, renal function, hemodynamic
      instability, and metabolic changes) and echocardiographic parameters (ductus
      arteriosus diameter, ductus arteriosus/weight ratio, left atrium/ aorta ratio,
      left ventricular diastolic diameter, and transductal flow direction, pattern and
      velocity) were analyzed. The clinical and echocardiographic parameters analyzed
      were considered statistically significant when p<0.05. RESULTS: In the 119
      neonates, the incidence of patent ductus arteriosus was 61.3%; 56 received
      treatment (46 pharmacological and 10 surgical treatment), 11 had spontaneous
      closure, 4 died, and 2 were discharged with patent ductus arteriosus. A higher
      incidence of chorioamnionitis, use of surfactant, lower weight and gestational
      age, sepsis, heart murmur, ventilatory support and worse oxygenation indices were
      observed in the neonates receiving treatment. The group with spontaneous closure
      had a smaller ductus arteriosus diameter, lower ductus arteriosus/weight ratio,
      and higher transductal flow velocity. CONCLUSION: Based on clinical and
      echocardiographic parameters, the neonates with spontaneous closure of the ductus
      arteriosus could be differentiated from those who required treatment.

PMID- 24136759
TI  - Short-term effects of moderate intensity physical activity in patients with
      metabolic syndrome.
AB  - OBJECTIVES: To evaluate whether a short-term moderate intensity exercise program
      could change inflammatory parameters, and improve different components of
      metabolic syndrome in sedentary patients. METHODS: Sixteen patients completed the
      12-week program of supervised exercise, which consisted of a 40 to 50 minutes of
      walking, 3 times a week, reaching 50 to 60% of the heart rate reserve. The
      parameters evaluated before and after intervention were waist circumference,
      systolic and diastolic blood pressure, triglycerides, LDL cholesterol, HDL
      cholesterol, total cholesterol, C-reactive protein and interleukin 8. RESULTS:
      There was a significant reduction in waist circumference (102.1+/-7.5cm to
      100.8+/-7.4cm; p=0.03) and in body mass index (29.7+/-3.2kg/m2 versus 29.3+/
      3.5kg/m2; p=0.03). Systolic blood pressure dropped from 141+/-18 to 129+/-13mmHg
      and diastolic from 79+/-12 to 71+/-10mmHg (with p<0.05 for both). No changes were
      observed on total cholesterol, LDL cholesterol and triglycerides, although HDL
      cholesterol levels improved, from 45.5+/-6.0 to 49.5+/-9.8mg/dL (p=0.02). There
      was a trend toward reduction of C-reactive protein (8.3%; p=0.07) and interleukin
      8 levels (17.4%; p=0.058). The improvement in cardiovascular capacity was
      demonstrated by an increase of 13% in estimated volume of oxygen (p<0.001).
      CONCLUSION: Benefits of aerobic exercise of moderate intensity were seen within
      only 12 weeks of training in sedentary patients with metabolic syndrome.
      Considering the easy self-applicability and proven metabolic effects, an exercise
      program could be a first approach to sedentary patients with metabolic syndrome.

PMID- 24136760
TI  - Factors that interfere the medication compliance in hypertensive patients.
AB  - OBJECTIVE: To characterize the factors that interfere in drug treatment
      compliance in a group of individuals with arterial hypertension. METHODS: A non
      experimental descriptive study that analyzed a sample of 80 patients diagnosed
      with arterial hypertension, who underwent medical treatment and were admitted to
      a university hospital during the period from March to May 2009. To collect data,
      the Instrument for Evaluation of Attitudes Regarding Taking Medication was
      applied. RESULTS: In the studied population, 45.1% had sufficient degree of
      compliance to drug therapy. Individuals with controlled blood pressure, females,
      white, single, married or widowed, retired, aged between 40 and 59 years, and
      those aged above 80 years were the interviewees who answered positively regarding
      compliance and follow-up of drug therapy. CONCLUSION: Despite the fact that the
      number of factors that facilitate the process of compliance to drug treatment is
      greater than the number of complicating factors, we found that more than half of
      the patients surveyed had an insufficient degree of compliance with drug
      treatment for high blood pressure, which demonstrates the need to develop studies
      aimed to identify these factors and their contribution to the promotion of
      patient autonomy, acceptance, awareness and adaptation regarding their illness.

PMID- 24136761
TI  - Assessing prognosis of pulmonary embolism using tissue-Doppler echocardiography
      and brain natriuretic peptide.
AB  - OBJECTIVE: To assess prognosis of pulmonary thromboembolism using tissue Doppler
      echocardiography and brain natriuretic peptide. METHODS: Patients aged over 18
      years were evaluated within 24 hours of confirmed diagnosis (chest
      tomography/pulmonary scintigraphy) of pulmonary embolism using two-dimensional
      echocardiography and tissue Doppler for right ventricular systolic (s')
      velocities, strain, tissue tracking and myocardial performance index. Plasma
      brain natriuretic peptide was also obtained within 24 hour. The influence of
      echocardiographic and clinical variables on mortality was examined (up to 12
      months) using Cox regression analysis. RESULTS: Out of 118 patients, 100 patients
      were included in the study (60 males, aged 55+/-17 years). Right ventricular
      dysfunction was observed in 28% using two-dimensional echocardiography. Tissue
      Doppler right ventricular variables (s' velocities, tissue tracking and strain)
      were decreased only for patients with right ventricular dysfunction, whereas
      myocardial performance index and systolic pulmonary artery pressure were
      increased. Mean brain natriuretic peptide value was 66+/-111pg/mL, also increased
      in patients with right ventricular dysfunction (136+/-146pg/mL). Mortality was
      11% and related to age, malignancy and brain natriuretic peptide levels. The only
      echocardiographic variables capable of predicting events by univariate analysis
      were pulmonary pressure and right ventricular s' velocity. However, multivariate
      analysis showed only malignancy to predict mortality in this group. CONCLUSION:
      Lower tissue Doppler systolic velocities and elevated brain natriuretic peptide
      levels are associated with poorer prognosis in patients with pulmonary
      thromboembolism; but only malignancy emerged as an independent predictor of
      mortality.

PMID- 24136762
TI  - Clinical evolution of mediastinitis in patients undergoing adjuvant hyperbaric
      oxygen therapy after coronary artery bypass surgery.
AB  - OBJECTIVE: To evaluate the use of hyperbaric oxygen therapy as an adjunctive
      treatment in mediastinitis after coronary artery bypass surgery. METHODS: This is
      a retrospective descriptive study, performed between October 2010 and February
      2012. Hyperbaric oxygen therapy was indicated in difficult clinical management
      cases despite antibiotic therapy. RESULTS: We identified 18 patients with
      mediastinitis during the study period. Thirty three microorganisms were isolated,
      and polymicrobial infection was present in 11 cases. Enterobacteriaceae were the
      most prevalent pathogens and six were multi-resistant agents. There was only 1
      hospital death, 7 months after the oxygen therapy caused by sepsis, unrelated to
      hyperbaric oxygen therapy. This treatment was well-tolerated. CONCLUSION: The
      initial data showed favorable clinical outcomes.

PMID- 24136763
TI  - Safety and efficacy of biolimus-eluting stent with biodegradable polymer:
      insights from EINSTEIN (Evaluation of Next-generation drug-eluting STEnt IN
      patients with coronary artery disease) Registry.
AB  - OBJECTIVE: To evaluate the incidence of major adverse cardiac events (cardiac
      death, or acute myocardial infarct, or target vessel revascularization) at one
      year in "real world" patients. METHODS: The EINSTEIN registry is an
      observational, prospective, single center study that consecutively included 103
      patients (152 lesions) treated with the BiomatrixTM stent, a biolimus A9-eluting
      stent with biodegradable polymer. RESULTS: The mean age was 65.0+/-12.4 years;
      male gender represented 83.5% of the patients; and 37.9% of them were diabetic.
      At one-year, major adverse cardiac events occurred in 11.7% of the patients,
      including 2.9% of cardiac death, 4.9% of with non ST- segment elevation acute
      myocardial infarction, and 3.9% of target vessel revascularization. Stent
      thrombosis occurred in only 1% (1 patient) at one-yearfollow-up. CONCLUSION: The
      present Registry suggests that new generation biolimus A9 drug-eluting stents are
      safe and effective in a "real world", all-comers patients, showing low rates of
      major cardiac adverse events on long-term follow-up.

PMID- 24136764
TI  - Effect of implementing an acute myocardial infarction guideline on quality
      indicators.
AB  - OBJECTIVE: To evaluate the compliance rates to quality of care indicators along
      the implementation of an acute myocardial infarction clinical practice guideline.
      METHODS: A clinical guideline for acute myocardial infarction was introduced on
      March 1st, 2005. Patients admitted for acute myocardial infarction from March
      1st, 2005 to December 31st, 2012 (n=1,431) were compared to patients admitted for
      acute myocardial infarction before the implementation of the protocol (n=306).
      Compliance rates to quality of care indicators (ASA prescription on hospital
      admission and discharge, betablockers on discharge and door-to-balloon time) as
      well as the length of hospital stay and in-hospital mortality were compared
      before and after the implementation of the clinical guideline. RESULTS: The rates
      of ASA prescription on admission, on discharge and of betablockers were higher
      after guideline implementation: 99.6% versus 95.8% (p<0.001); 99.1% versus 95.8%
      (p<0.001); and 95.9% versus 81.7% (p<0.001), respectively. ASA prescription rate
      increased over time, reaching 100% from 2009 to 2012. Door-to-balloon time after
      versus before implementation was of 86(32) minutes versus 93(51) (p=0.20). The
      length of hospital stay after the implementation versus before was of 6(6) days
      versus 6(4) days (p=0.34). In-hospital mortality was 7.6% (before the
      implementation), 8.7% between 2005 and 2008, and 5.3% between 2009 and 2012,
      (p=0.04). CONCLUSION: The implementation of an acute myocardial infarction
      clinical practice guideline was associated with an increase in compliance to
      quality of care indicators.

PMID- 24136765
TI  - Very late stent thrombosis with bare-metal stent: identifying severe stent
      malapposition and underexpansion by intravascular ultrasound.
AB  - A 60-year-old man with a history of implantation of two bare-metal stents 2 years
      prior presented to the emergency department with new-onset chest pain. He has
      been regularly taking angiotensinconverting enzyme inhibitors, beta blockers and
      aspirin. Aspirin was suspended for 10 days prior to the current hospitalization
      in order to perform surgery to remove a kidney tumor. He underwent coronary
      angiography, which revealed a right coronary artery with a distal intraluminal
      defect within the stents, suggesting thrombus. Intravascular ultrasound
      demonstrated a severe malapposition and underexpansion throughout the entire
      length of the stents containing thrombus. In this case, the mechanisms of very
      late stent thrombosis after bare-metal stent most likely were a combination of
      mechanical factors (severe stent undersizing during the index procedure) and
      pharmacological factors (aspirin discontinuation). 

PMID- 24136766
TI  - Anomalous right coronary artery arising from the pulmonary artery and
      constrictive pericarditis: an unusual association.
AB  - The association of anomalous right coronary artery originating from the pulmonary
      artery and constrictive pericarditis has never been showed in the literature. We
      present the first case of this unusual association in a patient with right heart
      failure. After diagnosis, the patient was referred to surgery and underwent
      phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic
      artery to right coronary artery; and ligation of the anomalous origin of the
      right coronary artery from the pulmonary artery. Such procedures solved the
      potential risk of sudden death related to anomalous right coronary artery
      originating from the pulmonary artery and alleviated the symptoms of heart
      failure caused by constrictive pericarditis. 

PMID- 24136767
TI  - Caseous calcification of the mitral annulus: case report.
AB  - We present a rare case of probable caseous calcification of the mitral. This
      pathology is more frequently detected in asymptomatic women older than 70 years.
      To recognize this image is important because echocardiography is the easiest way
      to elucidate this diagnosis, and more importantly because this structure could be
      easily misdiagnosed as tumors, thrombus and vegetations, which are much more
      common. Normally, it has a benign evolution, and the correct diagnosis is crucial
      to avoid unnecessary surgical interventions. 

PMID- 24136768
TI  - Streptococcus gallolyticus infective endocarditis in a patient with systemic
      lupus erythematosus: a three-dimensional echocardiography evaluation.
AB  - A 42 year-old woman was referred to our hospital with a history of fever and poor
      general status for the last 30 days. She presented tachycardia and a systolic
      apical murmur. Laboratory tests revealed leukocytosis of 13,100/mL, hemoglobin of
      8.4g/dL and positive systemic lupus erythematosus antibodies (anti-Ro/SSA, anti
      La/SSB, anticardiolipin, and antinuclear antibodies); blood culture was positive
      for Streptococcus gallolyticus. Three-dimensional transesophageal
      echocardiography was performed and revealed multiple mitral valve vegetations,
      with leaflet perforation and important mitral regurgitation, as well as large
      aortic vegetation, with cusp perforation and severe regurgitation. Additionally,
      a small vegetation was observed on the tricuspid valve, which presented moderate
      regurgitation. Threedimensional transesophageal echocardiography provides
      appropriate visualization of complications resulting from infectious
      endocarditis. 

PMID- 24136769
TI  - Vascular calcification: pathophysiology and clinical implications.
AB  - Vascular calcification in coronary artery disease is gaining importance, both in
      scientific research and in clinical and imaging applications. The calcified
      plaque is considered the most relevant form of atherosclerosis within the
      coronary artery tree and is frequently a challenge for percutaneous intervention.
      Recent studies showed that plaque calcification is dynamic and is strictly
      related to the degree of vascular inflammation. Several inflammatory factors
      produced during the different phases of atherosclerosis induce the expression and
      activation of osteoblastic cells located within the arterial wall, which, in
      turn, promote the deposit of calcium. The vascular smooth muscle cells have an
      extraordinary capacity to undergo osteoblastic phenotypical differentiation.
      There is no doubt that the role of these factors, as well as the elements of
      genomics and proteomics, could be a vital strategic point in prevention and
      treatment. Within this context, we conducted an updating review on coronary
      calcification focused on pathophysiology, experimental models, and clinical
      implications of vascular calcification.

PMID- 24136770
TI  - Decompensated heart failure.
AB  - Heart failure is a disease with high incidence and prevalence in the population.
      The costs with hospitalization for decompensated heart failure reach
      approximately 60% of the total cost with heart failure treatment, and mortality
      during hospitalization varies according to the studied population, and could
      achieve values of 10%. In patients with decompensated heart failure, history and
      physical examination are of great value for the diagnosis of the syndrome, and
      also can help the physician to identify the beginning of symptoms, and give
      information about etiology, causes and prognosis of the disease. The initial
      objective of decompensated heart failure treatment is the hemodynamic and
      symptomatic improvement preservation and/or improvement of renal function,
      prevention of myocardial damage, modulation of the neurohormonal and/or
      inflammatory activation and control of comorbidities that can cause or contribute
      to progression of the syndrome. According to the clinical-hemodynamic profile, it
      is possible to establish a rational for the treatment of decompensated heart
      failure, individualizing the proceedings to be held, leading to reduction in the
      period of hospitalization and consequently reducing overall mortality. 

PMID- 24136771
TI  - Contrast echocardiography in myocardial infarction.
AB  - The contrast agents used in ultrasound are approved for several clinical
      situations. New echocardiographic techniques, such as harmonic imaging and power
      pulse inversion imaging, can improve the visualization of microbubbles. In this
      article we discuss the early development of contrast echocardiography, new
      technologies that help improve image acquisition and its practical role in the
      assessment of myocardial infarction. 

PMID- 24136772
TI  - Saphenous vein graft thrombus findings by scanning electron microscopy in a
      patient with acute myocardial infarction.

PMID- 24136773
TI  - Coronary computed tomography angiography with 320-row detector and using the AIDR
      3D: initial experience.
AB  - Coronary computed tomography angiography (coronary CTA) is a powerful non
      invasive imaging method to evaluate coronary artery disease. Nowadays, coronary
      CTA estimated effective radiation dose can be dramatically reduced using state-of
      the-art scanners, such as 320-row detector CT (320-CT), without changing coronary
      CTA diagnostic accuracy. To optimize and further reduce the radiation dose, new
      iterative reconstruction algorithms were released recently by several CT
      manufacturers, and now they are used routinely in coronary CTA. This paper
      presents our first experience using coronary CTA with 320-CT and the Adaptive
      Iterative Dose Reduction 3D (AIDR-3D). In addition, we describe the current
      indications for coronary CTA in our practice as well as the acquisition standard
      protocols and protocols related to CT application for radiation dose reduction.
      In conclusion, coronary CTA radiation dose can be dramatically reduced following
      the "as low as reasonable achievable" principle by combination of exam indication
      and well-documented technics for radiation dose reduction, such as beta blockers,
      low-kV, and also the newest iterative dose reduction software as AIDR-3D. 

PMID- 24136774
TI  - Health management and evidence-based medicine.

PMID- 24136775
TI  - Updates in cardiology.

PMID- 24136776
TI  - Response to 'Fibromuscular dysplasia affecting a two-branched renal artery in a
      patient with a solitary kidney: case presentation'.

PMID- 24136778
TI  - Three-dimensional shape engineered, interfacial gelation of reduced graphene
      oxide for high rate, large capacity supercapacitors.

PMID- 24136777
TI  - Taxonomic and gene-centric metagenomics of the fecal microbiome of low and high
      feed conversion ratio (FCR) broilers.
AB  - Individual weight gain in broiler growers appears to vary, which may in part be
      due to variation in their gut microbiota. In this paper we analyse the fecal
      microbiota of low and high feed conversion ratio (FCR) broilers. After shotgun
      sequencing of the fecal microbiome, we used the SEED database to identify the
      microbial diversity and metabolic potential in low and high FCR birds. The domain
      level breakdown of our samples was bacteria (>95 %), eukaryotes (>2 %), archaea
      (>0.2 %), and viruses (>0.2 %). At the phylum level, Proteobacteria (78.83 % in
      low and 52.04 % in high FCR), Firmicutes (11.97 % in low and 27.53 % in high FCR)
      and Bacteroidetes (7.10 % in low FCR and 17.53 % in high FCR) predominated in the
      fecal microbial community. Poultry fecal metagenomes revealed the sequences
      related to 33 genera in both low and high FCR with significantly different
      proportion. Functional analysis revealed that genes for the metabolism of
      carbohydrates, amino acids and derivatives and protein metabolism were most
      abundant in SEED subsystem in both samples. Genes associated with stress,
      virulence, cell wall and cell capsule were also abundant. Indeed, genes
      associated with sulphur assimilation, flagellum and flagellar motility were over
      represented in low FCR birds. This information could help in developing
      strategies to improve feed efficiency and feed formulation for broiler chickens. 

PMID- 24136779
TI  - Associations between physical activity-related miRNAs and metabolic syndrome.
AB  - The aim of the study was to investigate the associations between physical
      activity (PA)-related miRNAs and metabolic syndrome (MetS). A case-control study
      was conducted in 209 subjects with MetS and 234 controls. The MetS was defined by
      the International Diabetes Foundation (IDF) criteria of 2005. Serum PA-related
      miRNAs were detected by quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) assays. Association analysis was performed by logistic
      regression models. The expression levels of miR-126 and miR-130a were lower in
      the highest metabolic equivalent hours per week (MET-h/week) quartile than in the
      lowest quartile [miR-126: Q5 vs. Q1, median (5-95%), 1.67 (0.54, 2.45) vs. 1.35
      (0.45, 2.45), p=0.012; miR-130a: Q5 vs. Q1, median (5-95%), 0.90 (0.44, 1.35) vs.
      0.53 (0.26, 1.01), p<0.001]. However, miR-197 exhibited a trend with increased
      MET-h/week [Q5 vs. Q1, median (5-95%), 1.35 (0.45, 2.63) vs. 2.18 (0.87, 4.77),
      p=0.009]. MiR-126 increased MetS risk significantly while the effect of miR-197
      was opposite (miR-126: OR=1.37, 95% CI 1.07-1.75; p=0.012; miR-197: OR=0.68, 95%
      CI 0.51-0.92; p=0.010). Individuals in the highest MET-h/week quartile had lower
      prevalence and odds rate of MetS compared with those in the lowest quartile (Q4
      vs. Q1: OR=0.58, 95% CI 0.33-1.05; p for trend=0.026). However, further
      adjustment of both PA associated miRNAs abolished that association. All these
      results suggested that the association between PA and MetS risk might partly
      depend on miR-126 and miR-197. 

PMID- 24136780
TI  - Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.
AB  - A marked decrease of klotho expression was observed in the kidney of
      streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It
      has been documented that klotho is the target gene of PPARgamma. However, the
      effect of PPARgamma agonist on klotho expression in kidney of STZ rats remains
      obscure. Thus, we used rosiglitazone (TZD) as PPARgamma agonist to investigate
      the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower
      levels of PPARgamma, klotho, and FGFR1 expressions in kidneys of STZ rats without
      the correction of hyperglycemia. Also, renal functions and structural defeats
      were improved by TZD treatment. Taken together, oral administration of TZD may
      improve STZ-induced diabetic nephropathy due to restoration of the expression of
      klotho axis through an increase in PPARgamma expression without changing blood
      glucose in rats. 

PMID- 24136781
TI  - Effects of progesterone and its metabolites on human granulosa cells.
AB  - The corpus luteum (CL) is under control of gonadotrophic hormones and produces
      progesterone, which is necessary for endometrial receptivity. Recent studies have
      shown that progesterone and its metabolites are involved in cell proliferation
      and apoptosis of cancer cells. Here weanalyzed the role of progesterone and its
      meta-bolites on luteinized granulosa cells (LGC) by FACS analysis and
      quantitative Real-Time PCR. We detected the mRNA of the progesterone metabolizing
      genes SRD5A1, AKR1C1, and AKR1C2 in LGC. The stimulation of LGC with progesterone
      or progesterone metabolites did not show any effect on the mRNA expression of
      these genes. However, a downregulation of Fas expression was found to be
      accomplished by progesterone and human chorionic gonadotropin. Our findings do
      not support the concept of an effect of progesterone metabolites on LGCs.
      However, it suggests an antiapoptotic effect of hCG and progesterone during
      corpus luteum development by downregulation of Fas. 

PMID- 24136782
TI  - Improved temporal resolution for functional studies with reduced number of
      segments with three-dimensional echo planar imaging.
AB  - PURPOSE: To introduce a new k-space traversal strategy for segmented three
      dimensional echo planar imaging (3D EPI) that encodes two partitions per
      radiofrequency excitation, effectively reducing the number excitations used to
      acquire a 3D EPI dataset by half. METHODS: The strategy was evaluated in the
      context of functional MRI applications for: image quality compared with segmented
      3D EPI, temporal signal-to-noise ratio (tSNR) (the ability to detect resting
      state networks compared with multislice two-dimensional (2D) EPI and segmented 3D
      EPI, and temporal resolution (the ability to separate cardiac- and respiration
      related fluctuations from the desired blood oxygen level-dependent signal of
      interest). RESULTS: Whole brain images with a nominal voxel size of 2 mm
      isotropic could be acquired with a temporal resolution under half a second using
      traditional parallel imaging acceleration up to 4* in the partition-encode
      direction and using novel data acquisition speed-up of 2* with a 32-channel coil.
      With 8* data acquisition speed-up in the partition-encode direction, 3D reduced
      excitations (RE)-EPI produced acceptable image quality without introduction of
      noticeable additional artifacts. Due to increased tSNR and better
      characterization of physiological fluctuations, the new strategy allowed
      detection of more resting state networks compared with multislice 2D-EPI and
      segmented 3D EPI. CONCLUSION: 3D RE-EPI resulted in significant increases in
      temporal resolution for whole brain acquisitions and in improved physiological
      noise characterization compared with 2D-EPI and segmented 3D EPI.

PMID- 24136783
TI  - Semiautomatic registration of digital histopathology images to in vivo MR images
      in molded and unmolded prostates.
AB  - PURPOSE: To evaluate a semiautomatic software-based method of registering in vivo
      prostate MR images to digital histopathology images using two approaches: (i) in
      which the prostates were molded to simulate distortion due to the endorectal
      imaging coil before fixation, and (ii) in which the prostates were not molded.
      MATERIALS AND METHODS: T2-weighted MR images and digitized whole-mount
      histopathology images were acquired for 26 patients with biopsy-confirmed
      prostate cancer who underwent radical prostatectomy. Ten excised prostates were
      molded before fixation. A semiautomatic method was used to align MR images to
      histopathology. Percent overlap between MR and histopathology images, as well as
      distances between corresponding anatomical landmarks were calculated and used to
      evaluate the registration technique for molded and unmolded cases. RESULTS: The
      software successfully morphed histology-based prostate images into corresponding
      MR images. Percent overlap improved from 80.4 +/- 5.8% before morphing to 99.7 +/
      0.62% post morphing. Molded prostates had a smaller distance between landmarks
      (1.91 +/- 0.75 mm) versus unmolded (2.34 +/- 0.68 mm), P < 0.08. CONCLUSION:
      Molding a prostate before fixation provided a better alignment of internal
      structures within the prostate, but this did not reach statistical significance.
      Software-based morphing allowed for nearly complete overlap between the pathology
      slides and the MR images.

PMID- 24136784
TI  - Molecular architecture of Streptococcus pneumoniae surface thioredoxin-fold
      lipoproteins crucial for extracellular oxidative stress resistance and
      maintenance of virulence.
AB  - The respiratory pathogen Streptococcus pneumoniae has evolved efficient
      mechanisms to resist oxidative stress conditions and to displace other bacteria
      in the nasopharynx. Here we characterize at physiological, functional and
      structural levels two novel surface-exposed thioredoxin-family lipoproteins,
      Etrx1 and Etrx2. The impact of both Etrx proteins and their redox partner
      methionine sulfoxide reductase SpMsrAB2 on pneumococcal pathogenesis was assessed
      in mouse virulence studies and phagocytosis assays. The results demonstrate that
      loss of function of either both Etrx proteins or SpMsrAB2 dramatically attenuated
      pneumococcal virulence in the acute mouse pneumonia model and that Etrx proteins
      compensate each other. The deficiency of Etrx proteins or SpMsrAB2 further
      enhanced bacterial uptake by macrophages, and accelerated pneumococcal killing by
      H2 O2 or free methionine sulfoxides (MetSO). Moreover, the absence of both Etrx
      redox pathways provokes an accumulation of oxidized SpMsrAB2 in vivo. Taken
      together our results reveal insights into the role of two extracellular electron
      pathways required for reduction of SpMsrAB2 and surface-exposed MetSO.
      Identification of this system and its target proteins paves the way for the
      design of novel antimicrobials. 

PMID- 24136785
TI  - Racial and socioeconomic disparities in pediatric and young adult liver
      transplant outcomes.
AB  - Racial and socioeconomic disparities exist in liver transplantation (LT) outcomes
      among adults, but little research exists for pediatric LT populations. We
      examined racial differences in graft survival and mortality within a
      retrospective cohort of pediatric and young adult LT recipients at a large
      children's transplant center in the Southeast between 1998 and 2011. The
      association between race/ethnicity and rates of graft failure and mortality was
      examined with Cox proportional hazards models that were adjusted for demographic
      and clinical factors as well as individual-level and census tract-level
      socioeconomic status (SES). Among the 208 LT recipients, 51.0% were white, 34.6%
      were black, and 14.4% were other race/ethnicity. Graft survival and patient
      survival were higher for whites versus minorities 1, 3, 5, and 10 years after
      transplantation. The 10-year graft survival rates were 84% [95% confidence
      interval (CI) = 76%-91%] for white patients, 60% (95% CI = 46%-74%) for black
      patients, and 49% (95% CI = 23%-77%) for other race/ethnicity patients. The 10
      year patient survival rates were 92% (95% CI = 84%-96%), 65% (95% CI = 52%-79%),
      and 76% (95% CI = 54%-97%) for the white, black, and other race/ethnicity groups,
      respectively. In analyses adjusted for demographic, clinical, and socioeconomic
      characteristics, the rates of graft failure [black: hazard ratio (HR) = 2.59, 95%
      CI = 1.29-5.45; other: HR = 3.01, 95% CI = 1.23-7.35] and mortality (black: HR =
      4.24, 95% CI = 1.54-11.69; other: HR = 3.09, 95% CI = 0.78-12.19) were higher for
      minority groups versus whites. In conclusion, at a large pediatric transplant
      center in the Southeastern United States, racial/ethnic disparities exist in
      pediatric and young adult LT outcomes that are not fully explained by measured
      SES and clinical factors.

PMID- 24136786
TI  - IFN-gamma deficiency attenuates hepatic inflammation and fibrosis in a
      steatohepatitis model induced by a methionine- and choline-deficient high-fat
      diet.
AB  - Cytokines play important roles in all stages of steatohepatitis, including
      hepatocyte injury, the inflammatory response, and the altered function of
      sinusoidal cells. This study examined the involvement of a major inflammatory
      cytokine, interferon-gamma (IFN-gamma), in the progression of steatohepatitis. In
      a steatohepatitis model by feeding a methionine- and choline-deficient high-fat
      (MCDHF) diet to both wild-type and IFN-gamma-deficient mice, the liver histology,
      expression of genes encoding inflammatory cytokines, and fibrosis-related markers
      were examined. To analyze the effects of IFN-gamma on Kupffer cells in vitro, we
      examined the tumor necrosis factor-alpha (TNF-alpha) production by a mouse
      macrophage cell line. Forty two days of MCDHF diet resulted in weight loss,
      elevated aminotransferases, liver steatosis, and inflammation in wild-type mice.
      However, the IFN-gamma-deficient mice exhibited less extensive changes. RT-PCR
      revealed that the expression of tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta, inducible nitric oxide synthase, interleukin-4
      and osteopontin were increased in wild-type mice, although they were suppressed
      in IFN-gamma-deficient mice. Seventy days of MCDHF diet induced much more liver
      fibrosis in wild-type mice than in IFN-gamma-deficient mice. The expression
      levels of fibrosis-related genes, alpha-smooth muscle actin, type I collagen,
      tissue inhibitor of matrix metalloproteinase-1, and matrix metalloproteinase-2,
      were dramatically increased in wild-type mice, whereas they were significantly
      suppressed in IFN-gamma-deficient mice. Moreover, in vitro experiments showed
      that, when RAW 264.7 macrophages were treated with IFN-gamma, they produced TNF
      alpha in a dose-dependent manner. The present study showed that IFN-gamma
      deficiency might inhibit the inflammatory response of macrophages cells and
      subsequently suppress stellate cell activation and liver fibrosis. These findings
      highlight the critical role of IFN-gamma in the progression of steatohepatitis. 

PMID- 24136787
TI  - Strain-specific suppression of microRNA-320 by carcinogenic Helicobacter pylori
      promotes expression of the antiapoptotic protein Mcl-1.
AB  - Helicobacter pylori is the strongest risk factor for gastric cancer, and strains
      harboring the cag pathogenicity island, which translocates the oncoprotein CagA
      into host cells, further augment cancer risk. We previously reported that in vivo
      adaptation of a noncarcinogenic H. pylori strain (B128) generated a derivative
      strain (7.13) with the ability to induce adenocarcinoma, providing a unique
      opportunity to define mechanisms that mediate gastric carcinogenesis. MicroRNAs
      (miRNAs) are small noncoding RNAs that regulate expression of oncogenes or tumor
      suppressors and are frequently dysregulated in carcinogenesis. To identify miRNAs
      and their targets involved in H. pylori-mediated carcinogenesis, miRNA
      microarrays were performed on RNA isolated from gastric epithelial cells
      cocultured with H. pylori strains B128, 7.13, or a 7.13 cagA(-) isogenic mutant.
      Among 61 miRNAs differentially expressed in a cagA-dependent manner, the tumor
      suppressor miR-320 was significantly downregulated by strain 7.13. Since miR-320
      negatively regulates the antiapoptotic protein Mcl-1, we demonstrated that H.
      pylori significantly induced Mcl-1 expression in a cagA-dependent manner and that
      suppression of Mcl-1 results in increased apoptosis. To extend these results,
      mice were challenged with H. pylori strain 7.13 or its cagA(-) mutant; consistent
      with cell culture data, H. pylori induced Mcl-1 expression in a cagA-dependent
      manner. In human subjects, cag(+) strains induced significantly higher levels of
      Mcl-1 than cag(-) strains, and Mcl-1 expression levels paralleled the severity of
      neoplastic lesions. Collectively, these results indicate that H. pylori
      suppresses miR-320, upregulates Mcl-1, and decreases apoptosis in a cagA
      dependent manner, which likely confers an increased risk for gastric
      carcinogenesis.

PMID- 24136788
TI  - Modulation of NF-kappaB and Nrf2 control of inflammatory responses in FHs 74 Int
      cell line is tocopherol isoform-specific.
AB  - The present study investigates the relative ability of alpha-, gamma-, and delta
      tocopherol (Toc) to modulate cell signaling events that are associated with
      inflammatory responses in fetal-derived intestinal (FHs 74 Int) cells. Secretion
      of the proinflammatory cytokine IL-8 in FHs 74 Int cells was stimulated in the
      following order: alpha-Toc<gamma-Toc<delta-Toc. A similar proinflammatory
      response was observed when inflammation was induced in FHs 74 Int cells.
      Modulation of IL-8 expression by Toc corresponded to an isoform-specific
      modulation of NF-kappaB and nuclear factor-erythroid 2-related factor 2 (Nrf2)
      cell signaling pathways involved in expression of proinflammatory cytokines and
      antioxidant enzymes, respectively. delta-Toc and, to a lesser extent, gamma-Toc
      activated NF-kappaB and Nrf2 signaling, as indicated by the greater nuclear
      translocation of transcription factors. Activation of NF-kappaB signaling by
      gamma- and delta-Toc was accompanied by upregulation of NF-kappaB target genes,
      such as IL-8 and prostaglandin-endoperoxide synthase 2, with and without a prior
      IFNgamma-PMA challenge. Nevertheless, gamma- and delta-Toc, particularly delta
      Toc, concurrently downregulated glutamate-cysteine ligase, a Nrf2 target gene
      that encodes for glutathione biosynthesis. This observation was substantiated by
      confirmation that gamma- and delta-Toc were effective at decreasing glutamate
      cysteine ligase protein expression and cellular glutathione content.
      Downregulation of glutathione content in fetal intestinal cells corresponded to
      induction of apoptosis-mediated cytotoxicity. In conclusion, gamma- and delta-Toc
      are biologically active isoforms of vitamin E and show superior bioactivity to
      alpha-Toc in modulating cell signaling events that contribute to a
      proinflammatory response in fetal-derived intestinal cells.

PMID- 24136789
TI  - Gut-derived short-chain fatty acids are vividly assimilated into host
      carbohydrates and lipids.
AB  - Acetate, propionate, and butyrate are the main short-chain fatty acids (SCFAs)
      that arise from the fermentation of fibers by the colonic microbiota. While many
      studies focus on the regulatory role of SCFAs, their quantitative role as a
      catabolic or anabolic substrate for the host has received relatively little
      attention. To investigate this aspect, we infused conscious mice with
      physiological quantities of stable isotopes [1-(13)C]acetate, [2
      (13)C]propionate, or [2,4-(13)C2]butyrate directly in the cecum, which is the
      natural production site in mice, and analyzed their interconversion by the
      microbiota as well as their metabolism by the host. Cecal interconversion,
      pointing to microbial cross-feeding, was high between acetate and butyrate, low
      between butyrate and propionate, and almost absent between acetate and
      propionate. As much as 62% of infused propionate was used in whole body glucose
      production, in line with its role as gluconeogenic substrate. Conversely, glucose
      synthesis from propionate accounted for 69% of total glucose production. The
      synthesis of palmitate and cholesterol in the liver was high from cecal acetate
      (2.8 and 0.7%, respectively) and butyrate (2.7 and 0.9%, respectively) as
      substrates, but low or absent from propionate (0.6 and 0.0%, respectively). Label
      incorporation due to chain elongation of stearate was approximately eightfold
      higher than de novo synthesis of stearate. Microarray data suggested that SCFAs
      exert a mild regulatory effect on the expression of genes involved in hepatic
      metabolic pathways during the 6-h infusion period. Altogether, gut-derived
      acetate, propionate, and butyrate play important roles as substrates for glucose,
      cholesterol, and lipid metabolism. 

PMID- 24136790
TI  - Main effect and interactions of brain regions and gender in the calculation of
      volumetric asymmetry indices in healthy human brains: ANCOVA analyses of in vivo
      3T MRI data.
AB  - INTRODUCTION: Macroanatomical right-left hemispheric differences in the brain are
      termed asymmetries, although there is no clear information on the global
      influence of gender and brain-regions. The aim of this study was to evaluate the
      main effects and interactions of these variables on the measurement of volumetric
      asymmetry indices (VAIs). MATERIALS AND METHODS: Forty-seven healthy young-adult
      volunteers (23 males, 24 females) agreed to undergo brain magnetic resonance
      imaging in a 3T scanner. Image post processing using voxel-based volumetry
      allowed the calculation of 54 VAIs from the frontal, temporal, parietal and
      occipital lobes, limbic system, basal ganglia, and cerebellum for each cerebral
      hemisphere. Multivariate ANCOVA analysis calculated the main effects and
      interactions on VAIs of gender and brain regions controlling the effect of age.
      RESULTS: The only significant finding was the main effect of brain regions (F (6,
      9373.605) 44.369, P < .001; partial eta2 = .101, and power of 1.0), with no
      significant interaction between gender and brain regions (F (6, 50.517) .239, P =
      .964). CONCLUSION: Volumetric asymmetries are present across all brain regions,
      with larger values found in the limbic system and parietal lobe. The absence of a
      significant influence of gender and age in the evaluation of the numerous
      measurements generated by multivariate analyses in this study should not
      discourage researchers to report and interpret similar results, as this topic
      still deserves further assessment.

PMID- 24136791
TI  - Hepatitis C virus serosorting in people who inject drugs: sorting out the
      details.

PMID- 24136792
TI  - Seroprevalence of herpes simplex virus types 1 and 2--United States, 1999-2010.
AB  - BACKGROUND: Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common
      infections with serious sequelae. HSV-1 is an increasingly important cause of
      genital herpes in industrialized countries. METHODS: Using nationally
      representative data from the National Health and Nutrition Examination Survey
      (NHANES), we examined HSV-1 and HSV-2 seroprevalence among 14- to 49-year-olds in
      the United States. We estimated seroprevalence in 1999-2004 and 2005-2010,
      stratified by sociodemographic characteristics and sexual behaviors. We also
      reviewed HSV-1 and HSV-2 seroprevalence from 1976-1980 to 2005-2010. RESULTS: In
      2005-2010, the seroprevalence of HSV-1 was 53.9%, and the seroprevalence of HSV-2
      was 15.7%. From 1999-2004 to 2005-2010, HSV-1 seroprevalence declined by nearly
      7% (P < .01), but HSV-2 seroprevalence did not change significantly. The largest
      decline in HSV-1 seroprevalence from 1999-2004 to 2005-2010 was observed among
      adolescents aged 14-19 years, among whom seroprevalence declined by nearly 23%,
      from 39.0% to 30.1% (P < .01). In this age group, HSV-1 seroprevalence declined
      >29% from 1976-1980 to 2005-2010 (P < .01). CONCLUSIONS: An increasing number of
      adolescents lack HSV-1 antibodies at sexual debut. In the absence of declines in
      HSV-2 infections, the prevalence of genital herpes may increase.

PMID- 24136793
TI  - The scarlet H.

PMID- 24136794
TI  - "To share or not to share?" Serosorting by hepatitis C status in the sharing of
      drug injection equipment among NHBS-IDU2 participants.
AB  - BACKGROUND: Persons who inject drugs (PWID) are at high risk for acquiring
      hepatitis C virus (HCV) infection. The Centers for Disease Control and Prevention
      estimates there are 17 000 new infections per year, mainly among PWID. This study
      examines injection equipment serosorting-considering HCV serostatus when deciding
      whether and with whom to share injection equipment. OBJECTIVE: To examine whether
      injection equipment serosorting is occurring among PWID in selected cities.
      METHODS: Using data from the National HIV Behavioral Surveillance System
      Injection Drug Users (NHBS-IDU2, 2009), we developed multivariate logistic
      regression models to examine the extent to which participants' self-reported HCV
      status is associated with their injection equipment serosorting behavior and
      knowledge of last injecting partner's HCV status. RESULTS: Participants who knew
      their HCV status were more likely to know the HCV status of their last injecting
      partner, compared to those who did not know their status (HCV+: adjusted odds
      ratio [aOR] 4.1, 95% confidence interval [CI], 3.4-4.9; HCV-: aOR 2.5, 95% CI,
      2.0-3.0). Participants who reported being HCV+, relative to those of unknown HCV
      status, were 5 times more likely to share injection equipment with a partner of
      HCV-positive status (aOR 4.8, 95% CI, 3.9-6.0). CONCLUSIONS: Our analysis
      suggests PWID are more likely to share injection equipment with persons of
      concordant HCV status.

PMID- 24136795
TI  - Facile regioselective synthesis of novel bis-thiazole derivatives and their
      antimicrobial activity.
AB  - The design and synthesis of several new bis-thiazoles 4a-h serving as bis-drugs
      in comparison with mono-heterocyclic analogs are described. These bis-drugs
      present superior medicinal and pharmacological activities against both gram
      negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive
      (Micrococcus luteus and Bacillus subtilis) bacteria, which are in general more
      sensitive to compounds with higher hydrophobicity. Compounds with higher
      hydrophobicity (4d and 4h) exhibited some activity against the gram-negative
      bacteria. 

PMID- 24136796
TI  - Selling amphetamine emblazoned athletic shirts v overselling amphetamines: a tale
      of two entrepreneurs.

PMID- 24136797
TI  - Candidate for NHS England top job says GP federations are the future.

PMID- 24136798
TI  - State opposition to Medicaid expansion will leave five million poor Americans
      without health cover, report says.

PMID- 24136799
TI  - India to set up 80 new units to boost medical research.

PMID- 24136800
TI  - Letter to the Editor: Mid-America Orthopaedic Association Physician in Training
      Award: Surgical technique: Pediatric supracondylar humerus fractures: a technique
      to aid closed reduction.

PMID- 24136801
TI  - The effect of infrapatellar fat pad excision on complications after minimally
      invasive TKA: a randomized controlled trial.
AB  - BACKGROUND: The infrapatellar fat pad is one of the structures that obscures
      exposure in minimally invasive total knee arthroplasty (MIS TKA). Most MIS TKA
      surgeons (and many surgeons who use other approaches as well) excise the fat pad
      for better exposure of the knee. There is still controversy about the result of
      fat pad excision on patella baja, pain, and function. QUESTIONS/PURPOSES: In the
      setting of a randomized controlled trial, we sought to determine whether
      infrapatellar fat pad excision during MIS TKA causes (1) patellar tendon
      shortening (as measured by patella baja); (2) increased anterior knee pain; (3)
      decreases in the Knee Society Score or functional subscore; or (4) more patella
      related complications. METHODS: We randomized 90 patients undergoing MIS TKA at
      one institution into two groups. In one group, 45 patients underwent MIS TKA with
      complete infrapatellar fat pad excision and in the other group, 45 patients
      received MIS TKA without infrapatellar fat pad excision. The patella was
      selectively resurfaced in these patients; there was no difference between the
      groups in terms of the percentage of patients whose patellae were resurfaced. We
      measured patellar tendon shortening, knee flexion, anterior knee pain, Knee
      Society Score (KSS), functional subscore, and patellar complications at
      preoperative and postoperative periods of 6 weeks, 3 months, 6 months, and 1
      year; complete followup data were available on 86% of patients (77 of 90) who
      were enrolled. RESULTS: At the final followup, no significant differences were
      observed in patellar tendon shortening, KSS, functional subscore, or knee flexion
      in either group. However, patients with their infrapatellar fat pad excised
      experienced more anterior knee pain (8.3% versus 0%; p = 0.03; 95% confidence
      interval, -0.007 to 0.174) at the end of the study. No patellar complications
      were found in either group. CONCLUSIONS: Infrapatellar fat pad excision in MIS
      TKA resulted in an increasing small percentage of patients with anterior knee
      pain after surgery. Surgeons should keep the fat pad if excellent exposure can be
      achieved but resect it if needed to improve exposure during TKA.

PMID- 24136802
TI  - CORR Insights (r): Coexisting lumbar spondylosis in patients undergoing TKA: how
      common and how serious?

PMID- 24136803
TI  - Assessing shoulder motion in children: age limitations to Mallet and ABC Loops.
AB  - BACKGROUND: Shoulder ROM and function of the shoulder are difficult to evaluate
      in young children. There has been no determination of the age at which children
      can comply with the current assessment tools in use, but doing so would be
      important, because it gives us more accurate insight into the development and
      assessment of shoulder functional ROM in young children. QUESTIONS/PURPOSES: We
      (1) determined whether age would limit the use of two different observational
      scales used to assess shoulder ROM and function in young children (the Mallet
      scale and the ABC Loops protocol); and (2) compared the two scales in terms of
      intra- and interobserver reliabilities. METHODS: Sixty-five able-bodied children
      (32 boys, 33 girls; mean age, 3.9 years; range, 0.5-7.0 years) were recruited
      from local preschools and evaluated using the Mallet scale and ABC Loops
      protocol. Children were assessed on their ability to complete the examinations
      and time to completion for each measurement protocol. Intra- and interobserver
      reliability was tested by percentage agreement. Forty-eight children (mean age,
      4.4 years; SD, 1.3 years) were able to complete the Mallet and ABC Loops
      measurement protocols; 17 children (mean age, 2.3 years; SD, 1.1 years) failed to
      complete either test. RESULTS: Younger children had more difficulty completing
      the examinations; there was a strong negative correlation between age and
      failure: probability of failure increased with decreasing age (Pearson r = 
      0.601, p < 0.001). Children who were able to complete one test were able to
      complete the other. Interobserver and intraobserver agreement was very high for
      both scales (in excess of 95% for all comparisons), and with the numbers
      available, there were no differences between the scales. CONCLUSIONS: The Mallet
      scale and ABC Loops protocol have high reliability metrics in children younger
      than 6 years, but very young children (those younger than 3 years) generally will
      not be able to complete the examinations. The ABC Loops test took longer to
      perform than the Mallet scale but may more comprehensively evaluate a child's
      functional capabilities. We therefore state that both assessment tools can be
      reliably used in children older than 3 years; we believe the ABC Loops gives a
      more accurate assessment of shoulder ROM.

PMID- 24136804
TI  - Osteogenic gene expression correlates with development of heterotopic
      ossification in war wounds.
AB  - BACKGROUND: Heterotopic ossification (HO) is a frequent complication of modern
      wartime extremity injuries. The biological mechanisms responsible for the
      development of HO in traumatic wounds remain elusive. QUESTION/PURPOSES: The aims
      of our study were to (1) characterize the expression profile of osteogenesis
      related gene transcripts in traumatic war wounds in which HO developed; and (2)
      determine whether expression at the mRNA level correlated with functional protein
      expression and HO formation. METHODS: Biopsy specimens from 54 high-energy
      penetrating extremity wounds obtained at the initial and final surgical
      debridements were evaluated. The levels of selected osteogenic-related gene
      transcripts from RNA extracts were assessed by quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis. As a result of its key role in
      osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was
      determined. RESULTS: The transcripts of 13 genes (ALPL [p = 0.006], BMP-2 [p <
      0.001], BMP-3 [p = 0.06], COL2A1 [p < 0.001], COLL10A1 [p < 0.001], COL11A1 [p =
      0.006], COMP [p = 0.02], CSF2 [p = 0.003], CSF3 [p = 0.012], MMP8 [p < 0.001],
      MMP9 [p = 0.014], SMAD1 [p = 0.024], and VEGFA [p = 0.017]) were upregulated
      greater than twofold in wounds in which HO developed compared with wounds in
      which it did not develop. Gene transcript expression of BMP-2 also correlated
      directly with functional protein expression in the wounds that formed HO (p =
      0.029). CONCLUSIONS: Important differences exist in the osteogenic gene
      expression profile of wounds in which HO developed compared with wounds in which
      it did not develop. The upregulation of multiple osteogenesis-related gene
      transcripts indicates the presence of a proosteogenic environment necessary for
      ectopic bone formation in traumatic wounds. CLINICAL RELEVANCE: Understanding the
      osteogenic environment associated with war wounds may allow for the development
      of novel therapeutic strategies for HO.

PMID- 24136806
TI  - Axillary view: arthritic glenohumeral anatomy and changes after ream and run.
AB  - BACKGROUND: The technique and results of shoulder arthroplasty are influenced by
      glenohumeral pathoanatomy. Although some authors advocate a routine preoperative
      CT scan to define this anatomy, ordering a CT scan substantially increases the
      cost and the radiation exposure for the patient. QUESTIONS/PURPOSES: We asked
      whether measurements of arthritic shoulders on a standardized axillary view are
      reliable; if postoperative radiographs can reliably show the changes in glenoid
      anatomy and glenohumeral relationships after shoulder arthroplasty, and if the
      axillary view can show differences in glenohumeral pathoanatomy in the different
      sexes and disease types. METHODS: These questions were addressed using cross
      sectional studies of 344 shoulders with different types of arthritis and of 128
      osteoarthritic shoulders having a ream and run arthroplasty (a glenohumeral
      arthroplasty that combines a noncemented humeral hemiarthroplasty with concentric
      reaming of the glenoid bone without implantation of a prosthetic glenoid
      component). Measurements of glenoid type, glenoid version, and glenohumeral
      contact were made on standardized axillary radiographs. Interobserver reliability
      was calculated, preoperative and postoperative measurements were compared, and
      morphologic differences were compared as stratified by sex and disease type.
      RESULTS: The measurements on axillary views showed a high degree of interobserver
      reliability and sensitivity to the changes effected by arthroplasty. The ream and
      run substantially corrected the glenoid type and point of glenohumeral contact.
      Male shoulders and shoulders with osteoarthritis had more type B glenoids (ie,
      those with posterior erosion and biconcavity of the glenoid), more retroversion,
      and a greater degree of posterior displacement of the point of glenohumeral
      contact. CONCLUSIONS: The axillary view provides a practical method of
      characterizing glenohumeral anatomy before and after surgery that is less costly
      and exposes the patient to less radiation than a CT scan. LEVEL OF EVIDENCE:
      Level IV, diagnostic study. See the Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24136805
TI  - High complication rate in revision total hip arthroplasty in juvenile idiopathic
      arthritis.
AB  - BACKGROUND: Revision total hip arthroplasty (THA) in patients with juvenile
      idiopathic arthritis (JIA) is challenging as a result of the patient's young age,
      systemic disease, multiple affected joints, small proportions, and bone loss. The
      intermediate- to long-term results of these surgeries remain unknown.
      QUESTIONS/PURPOSES: The purpose of this study is to determine the (1) functional
      outcomes; (2) surgical complications; and (3) frequency of reoperation or
      revision after revision THA for JIA. METHODS: We reviewed the records of all
      patients from one center who underwent revision THA for JIA who had a minimum of
      5 years of followup (mean, 9 years; range, 5-19 years). This resulted in a series
      of 24 revision THAs in 15 patients. All patients were Charnley Class C. Age at
      revision averaged 35 years (range, 21-53 years). The 20 acetabular and 12 femoral
      revision components included 15 cementless cups, five reconstruction/roof rings
      with a cemented cup, and four cemented and eight cementless femoral stems.
      RESULTS: The Harris hip scores improved from 54 (range, 34-85) to 77 (range, 37
      100) (p < 0.001). Complications included two proximal femoral fractures
      associated with severe osteolysis and one sciatic nerve palsy in a patient with
      severe acetabular deficiency. A total of seven hips (29%) required reoperation or
      revision surgery, including three for infection (one early and two late) and four
      for mechanical loosening. CONCLUSIONS: Revision THA in JIA is very challenging
      owing to patients' small proportions and compromised bone stock. The
      intraoperative and early complication rates are relatively high. Prognosis for
      long-term survivorship is guarded; limiting factors include periprosthetic
      osteolysis associated with older implants that used conventional polyethylene and
      cemented stems.

PMID- 24136807
TI  - Fixation versus replacement of radial head in terrible triad: is there a
      difference in elbow stability and prognosis?
AB  - BACKGROUND: Surgical treatment for terrible triad injuries of the elbow (defined
      as elbow dislocations with concomitant fractures of the radial head and coronoid)
      remains a challenging clinical problem. Specifically, the question of whether to
      repair or replace the radial head remains controversial. QUESTIONS/PURPOSES: We
      compared patients with terrible triad injuries of the elbow whose radial head
      fracture was treated with either internal fixation and internal fixation (ORIF)
      or radial head arthroplasty in terms of (1) clinical outcome measures (DASH and
      Broberg-Morrey scores, ROM), (2) elbow stability and radiographic signs of
      arthrosis, and (3) complications and reoperation rates. METHODS: Retrospective
      review identified 39 patients with terrible triad injuries and minimum 18-month
      complete clinical and radiographic followup (mean, 24 months; range, 18-53
      months). Patients were managed with a standard algorithm consisting of (1) repair
      (n = 9) or replacement (n = 30) of the radial head, (2) repair of the lateral
      ulnar collateral ligament, and (3) repair of the coronoid fracture. During the
      study period, the radial head generally was internally fixed when there were
      fewer than four articular fragments; otherwise, it was replaced. Evaluation
      included the DASH score, the Broberg-Morrey index, measurements of elbow
      stability and motion, and radiographic assessment for signs of arthrosis; chart
      review was performed for complications and reoperations. Complete followup was
      available on 87% (39 of 45 patients). RESULTS: There were no differences between
      groups in terms of ROM or elbow scores. All patients who underwent radial head
      arthroplasty at the index procedure had a stable elbow at final followup whereas
      three of nine patients who underwent ORIF were unstable (p = 0.009). However, 11
      patients who underwent arthroplasty demonstrated radiographic signs of arthrosis
      compared to none in the ORIF group (p = 0.04). Eleven patients (28%) underwent
      reoperation (seven arthroplasty, four ORIF) for various reasons. With the numbers
      available, there was no difference in reoperation rate between groups (p = 0.45).
      CONCLUSIONS: For terrible triad injuries, radial head arthroplasty afforded the
      ability to obtain elbow stability with comparable overall outcomes when compared
      to ORIF. As these injuries commonly occur in younger patients, longer-term
      studies will be required to ascertain whether the apparent benefits of radial
      head arthroplasty are offset by late complications of arthroplasty, such as
      loosening. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24136808
TI  - Editor's Spotlight/Take 5: What are the levels of evidence on which we base
      decisions for surgical management of lower extremity bone tumors?

PMID- 24136809
TI  - Letter to the Editor: Another look: Is there a flaw to current hip septic
      arthritis diagnostic algorithms?

PMID- 24136810
TI  - Ferroelectric domain wall injection.
AB  - Ferroelectric domain wall injection has been demonstrated by engineering of the
      local electric field, using focused ion beam milled defects in thin single
      crystal lamellae of KTiOPO4 (KTP). The electric field distribution (top) displays
      localized field hot-spots, which correlate with nucleation events (bottom).
      Designed local field variations can also dictate subsequent domain wall mobility,
      demonstrating a new paradigm in ferroelectric domain wall control. 

PMID- 24136811
TI  - Shale gas revolution: an opportunity for the production of biobased chemicals?

PMID- 24136812
TI  - Improved artery-vein separation with acceleration-dependent preparation for non
      contrast-enhanced magnetic resonance angiography.
AB  - PURPOSE: To compare the use of acceleration-dependent and velocity-dependent flow
      preparation for non-contrast-enhanced magnetic resonance angiography (NCE-MRA),
      investigating both image quality and the ability to discriminate between arteries
      and veins. We develop an acceleration-dependent NCE-MRA method known as
      acceleration dependent vascular anatomy for non-contrast-enhanced MRA (ADVANCE
      MRA). METHODS: Acceleration-dependent and velocity-dependent images were acquired
      using a constant and pulsatile flow-phantom and from the lower legs of six
      healthy volunteers and one patient with peripheral vascular disease. The
      volunteer images were assessed both by quantitative signal measurements and
      qualitative scoring by a radiologist. RESULTS: In the phantom, acceleration
      dependent preparation depicted pulsatile but not constant flow, while velocity
      dependent preparation depicted both. In the volunteers and the patient, the
      velocity-dependent preparation was unable to separate the arterial and venous
      signals completely, with some overlap of arterial and venous signals for all
      acquired flow sensitizations whereas the acceleration-dependent preparation gave
      complete artery-vein separation over a wide range of flow sensitizations.
      Acceleration-dependent preparation received the best overall qualitative scores
      for arterial image quality and venous contamination. CONCLUSION: Acceleration
      dependent NCE-MRA improves arterial image quality and reduces venous
      contamination, compared with velocity-dependent NCE-MRA, and warrants further
      investigation in patients.

PMID- 24136813
TI  - Differential diagnosis of benign and malignant distal biliary strictures: value
      of adding diffusion-weighted imaging to conventional magnetic resonance
      cholangiopancreatography.
AB  - PURPOSE: To determine the value of adding diffusion-weighted imaging (DWI) to
      conventional magnetic resonance cholangiopancreatography (MRCP) for
      differentiating benign from malignant distal biliary strictures. MATERIALS AND
      METHODS: Two independent readers reviewed three image sets (1: MRCP alone; 2:
      MRCP and DWI combined; and 3: MRCP, DWI, and contrast-enhanced T1-weighted
      imaging [T1WI] combined) of 60 patients with suspected distal biliary strictures
      and rated the probability of malignancy. Diagnostic performance and accuracy were
      compared using the receiver operating characteristic (ROC) curves and McNemar two
      tailed test. kappa coefficients were calculated to assess the interobserver
      agreement. RESULTS: The Az value and accuracy improved significantly after
      additional review of DWI for both readers: Az = 0.780 vs. 0.916 (P = 0.003) for
      Reader 1 and 0.784 vs. 0.853 (P = 0.037) for Reader 2; accuracy = 69% vs. 93% for
      Reader 1 (P < 0.001) and 57% vs. 85% for Reader 2 (P = 0.002). No significant
      difference in the Az values and accuracy was found between MRCP and DWI combined,
      and MRCP, DWI, and contrast-enhanced T1WI combined (P > 0.050). There was
      substantial interobserver agreement in all three image sets (kappa = 0.695
      0.732). CONCLUSION: The addition of DWI to MRCP significantly improved diagnostic
      accuracy in the characterization of distal biliary strictures.

PMID- 24136814
TI  - Combined lung and liver transplantation: analysis of a single-center experience.
AB  - Patients with end-stage lung disease complicated by cirrhosis are not expected to
      survive lung transplantation alone. Such patients are potential candidates for
      combined lung-liver transplantation (CLLT), however few reports document the
      indications and outcomes after CLLT. This is a review of a large single-center
      CLLT series. Eight consecutive CLLT performed during 2009-2012 were
      retrospectively reviewed. One patient received a third simultaneous heart
      transplant. Mean age was 42.5 +/- 11.5 years. Pulmonary indications included
      cystic fibrosis (CF) (n = 3), idiopathic pulmonary fibrosis (n = 2), alpha1
      antitrypsin deficiency (AATD) (n = 1) and pulmonary hypertension (n = 2). Liver
      indications were CF (n = 3), hepatitis C (n = 2), AATD (n = 1), cryptogenic (n =
      1), and cardiac/congestive (n = 1). Urgency was reflected by median lung
      allocation score (LAS) of 41 (36.0-89.0) and median predicted FEV1 of 25.7%.
      Median donor age was 25 (20-58) years with median cold ischemia times of 147
      minutes and 6.1 hours for lung and liver, respectively. Overall patient survival
      at 30 days, 90 days and 1 year was 87.5%, 75.0% and 71.4% respectively. One
      patient had evidence of acute lung rejection, and no patients had liver allograft
      rejection. Early postoperative mortalities (90 days) were caused by sepsis in 2
      recipients who exhibited the highest LAS of 69.9 and 89.0. The remaining
      recipients had a median LAS of 39.5 and 100% survival at 1-year. Median length of
      stay was 25 days (7-181). Complications requiring operative intervention included
      bile duct ischemia (n = 1) and bile leak (n = 1), ischemia of the bronchial
      anastomosis (n = 1), and necrotizing pancreatitis with duodenal perforation (n =
      1). This series reflects a large single-center CLLT experience. Sepsis is the
      most common cause of death. The procedure should be considered for candidates
      with LAS < 50.

PMID- 24136815
TI  - Rapid interaction of Helicobacter pylori with microvilli of the polar human
      gastric epithelial cell line NCI-N87.
AB  - Infection with Helicobacter pylori results often in chronic gastritis, gastric
      ulcers or even gastric tumor development. Little is known about the initial
      interaction between gastric epithelial cells and H. pylori. The aim of the
      present study was to analyze the initial host contact to the bacteria. Monolayers
      of the human gastric epithelial cell line NCI-N87 grown on porous membranes were
      used and the apical side of the epithelium was exposed to the H. pylori wild-type
      strain P1 for 1 hr. Many epithelial cells were colonized by bacteria within the
      period of 60 min. Using scanning electron microscopy we detected that the
      bacteria were in close contact with the epithelia via microvilli. Further,
      transmission electron microscopy of the contact sites revealed no difference in
      the morphology of the microvilli in comparison to those not attached to the
      bacteria. The present study demonstrates the importance of microvilli on apical
      epithelial cells during the initial contact of the host by colonizing H. pylori.

PMID- 24136816
TI  - Regional perfusion imaging using pTILT.
AB  - PURPOSE: To demonstrate the feasibility that the pseudo-continuous transfer
      insensitive labeling technique (pTILT) sequence can be modified to achieve
      regional perfusion imaging by either vessel-encoded or vessel-selective pTILT,
      similar to the regional perfusion imaging sequences using pseudo-continuous
      arterial spin labeling (pCASL). MATERIALS AND METHODS: Static phantom experiments
      were carried out to investigate the selectivity and efficiency of region-specific
      labeling by pTILT. The ability of the modified pTILT sequences to separate
      perfusion territories was also examined at two levels of the arterial tree on
      four healthy subjects: (i) the left and right internal carotid arteries (ICAs)
      and (ii) individual vascular territories of arteries above the circle of Willis
      (anterior cerebral artery [ACA], left and right middle cerebral arteries [MCAs]).
      RESULTS: In the phantom study, compared with non-region-specific pTILT, a
      labeling efficiency of 0.92 and 0.88 was measured at the target vessels using
      vessel-encoded and vessel-selective pTILT, respectively. In human studies, the
      perfusion territories of ACA, left and right MCA branches with estimated CBF of
      74.5 +/- 26.1, 65.9 +/- 7.2, and 72.3 +/- 14.5 mL/100 g/min, respectively, as
      well as more general left/right end territories (76.8 +/- 12.7 and 72.8 +/- 7.2
      mL/100 g/min), were clearly delineated by the modified pTILT sequences for
      regional perfusion imaging. CONCLUSION: Two regional perfusion imaging modules
      (vessel-encoded and vessel-selective) used in pCASL can also be adapted into the
      pTILT sequence, and our results confirmed that the region-specific pTILT sequence
      is capable of regional perfusion imaging to separate perfusion territories of
      major cerebral arteries.

PMID- 24136817
TI  - The electronic nature of the 1,4-beta-glycosidic bond and its chemical
      environment: DFT insights into cellulose chemistry.
AB  - The molecular understanding of the chemistry of 1,4-beta-glucans is essential for
      designing new approaches to the conversion of cellulose into platform chemicals
      and biofuels. In this endeavor, much attention has been paid to the role of
      hydrogen bonding occurring in the cellulose structure. So far, however, there has
      been little discussion about the implications of the electronic nature of the 1,4
      beta-glycosidic bond and its chemical environment for the activation of 1,4-beta
      glucans toward acid-catalyzed hydrolysis. This report sheds light on these
      central issues and addresses their influence on the acid hydrolysis of cellobiose
      and, by analogy, cellulose. The electronic structure of cellobiose was explored
      by DFT at the BB1 K/6-31++G(d,p) level. Natural bond orbital (NBO) analysis was
      performed to grasp the key bonding concepts. Conformations, protonation sites,
      and hydrolysis mechanisms were examined. The results for cellobiose indicate that
      cellulose is protected against hydrolysis not only by its supramolecular
      structure, as currently accepted, but also by its electronic structure, in which
      the anomeric effect plays a key role.

PMID- 24136818
TI  - Reduction of conformational mobility and aggregation in W60G beta2-microglobulin:
      assessment by 15N NMR relaxation.
AB  - The amyloid pathology associated with long-term haemodialysis is due to the
      deposition of beta2-microglobulin, the non-polymorphic light chain of class I
      major histocompatibility complex, that accumulates at bone joints into amyloid
      fibrils. Several lines of evidence show the relevance of the tryptophan residue
      at position 60 for the fibrillogenic transition of the protein. A comparative
      (15)N NMR relaxation analysis is presented for wild-type human beta2
      microglobulin and W60G beta2-microglobulin, i.e. the mutant with a glycyne
      replacing the natural tryptophan residue at position 60. The experimental data,
      collected at 11.4 T and 310 K, were analyzed by means of the reduced spectral
      density approach. Molecular dynamics (MD) simulations and corresponding
      thermodynamic integration, together with hydrodynamic calculations were performed
      to support data interpretation. The analysis results for the mutant protein are
      consistent with a reduced aggregation with respect to the wild-type counterpart,
      as a consequence of an increased conformational rigidity probed by either NMR
      relaxation and MD simulations. Although dynamics in solution is other than
      fibrillar competence, the assessed properties of the mutant protein can be
      related with its reduced ability of forming fibrils when seeded in 20%
      trifluoroethanol.

PMID- 24136819
TI  - Enhanced reactivity of a biomimetic iron(II) alpha-keto acid complex through
      immobilization on functionalized gold nanoparticles.

PMID- 24136820
TI  - Drug discovery alliances in India--indications, targets, and new chemical
      entities.
AB  - Global pharmaceutical and biotechnology companies have been building increasingly
      on the skills and services offered by Indian biotech companies through strategic
      collaborative partnerships and alliances to fuel their in-house discovery and
      development pipelines. With the exception of generic press releases, however,
      very little has been published on the process and progress of drug discovery
      itself, such as the targets or modes of action involved, nor on the scientific
      output of such collaborations, and therefore on new chemical entities coming out
      of India through research collaborations. This Essay provides an analytical
      review of recent patents, patent applications, and peer-reviewed publications of
      major research alliances. It aims at highlighting their scientific output as well
      as the considerable bandwidth of targets and therapeutic areas involved. 

PMID- 24136821
TI  - Orchid protocorm-like bodies are somatic embryos.
AB  - PREMISE OF THE STUDY: Protocorm-like bodies (PLBs) of orchids are important in
      orchid micropropagation and outwardly resemble somatic embryos in form and
      development. To determine whether PLBs are truly embryogenetic, we compared PLBs
      with somatic embryos and zygotic embryos to determine whether they had similar
      surface molecules and whether hydroxyproline-rich glycoprotein (HRGP) inhibitors
      similarly alter their growth. METHODS: Embryogenic calluses (ECs), zygotic
      embryos, and protocorms were collected for histological and histochemical studies
      with light microscopy. The presence of JIM11 and JIM20 epitopes was determined
      using immunodot blots and immunolocalization procedures. The importance of wall
      proteins in the formation of PLBs was investigated using 3,4-dehydro-l-proline
      (3,4-DHP), an inhibitor of HRGP biosynthesis. KEY RESULTS: At the early stages of
      PLB formation, the cytoplasm of the globular cell clusters and meristemoids took
      on a vacuolated appearance. Starch granules and protein bodies appeared, albeit
      transitory in nature. Positive localizations of JIM11 and JIM20 were noted in the
      embryogenic culture and developing PLBs similar to zygotic embryos. The inclusion
      of an inhibitor to HRGPs inhibited PLB formation. CONCLUSIONS: This study
      demonstrates that during the early stages of PLB formation, the cells show
      cytological characteristics and cell wall markers similar to zygotic embryo
      development, justifying the statement that PLBs are indeed somatic embryos of
      orchids. Thus, these results suggest that PLBs could be used as an experimental
      embryological system for physiological or molecular characterization.

PMID- 24136822
TI  - Predispersal seed predation is higher in a rare species than in its widespread
      sympatric congeners (Astragalus, Fabaceae).
AB  - PREMISE OF THE STUDY: Rare plants may be rare, in part, because they are more
      susceptible to damage by predispersal insect seed predators than widespread
      congeneric species; thus, seed predation may be an important determinant of plant
      rarity. Scant evidence exists to either support or reject this hypothesis,
      limiting our ability to predict herbivore effects on plant rarity. We used a
      comparative framework to test this hypothesis in rare-common, sympatric
      congeners. METHODS: We compared seed consumption by insect type and seed
      production among a rare Astragalus (Fabaceae) species and two sympatric,
      widespread congeners. We measured plant traits and tested whether traits were
      correlated with seed damage within and among rare-common species. KEY RESULTS:
      Seed predation was significantly higher in a rare species than in common
      congeners over 2 yr. Seed production per pod was significantly lower in the rare
      species. Seed weevils exclusively consumed seeds of the rare species. Higher seed
      predation in the rare species is related to a combination of factors: plant
      phenology, dispersal ability, and vigor; seed predator identity; and insect
      phenology. CONCLUSIONS: Our results support the hypothesis that a rare plant is
      more susceptible to seed predators than two common, sympatric congeners. Seed
      predator reduction is a promising management tool to increase seed-set,
      recruitment, and survival of the rare species. Further studies that compare rare
      common, sympatric congeners are greatly needed to broadly evaluate the hypothesis
      concerning rarity and susceptibility to seed predators and to inform conservation
      plans for rare species.

PMID- 24136823
TI  - A mechanism for suppression of the CDP-choline pathway during apoptosis.
AB  - Inhibition of the CDP-choline pathway during apoptosis restricts the availability
      of phosphatidylcholine (PtdCho) for assembly of membranes and synthesis of
      signaling factors. The N-terminal nuclear localization signal (NLS) in
      CTP:phosphocholine cytidylyltransferase (CCT)alpha is removed during apoptosis
      but the caspase(s) involved and the contribution to suppression of the CDP
      choline pathway is unresolved. In this study we utilized siRNA silencing of
      caspases in HEK293 cells and caspase 3-deficient MCF7 cells to show that caspase
      3 is required for CCTalpha proteolysis and release from the nucleus during
      apoptosis. CCTalpha-Delta28 (a caspase-cleaved mimic) expressed in CCTalpha
      deficient Chinese hamster ovary cells was cytosolic and had increased in vitro
      activity. However, [3H]choline labeling experiments in camptothecin-treated MCF7
      cells and MCF7 cells expressing caspase 3 (MCF7-C3) revealed a global suppression
      of the CDP-choline pathway that was consistent with inhibition of a step prior to
      CCTalpha. In camptothecin-treated MCF7 and MCF7-C3 cells, choline kinase activity
      was unaffected; however, choline transport into cells was reduced by 30 and 60%,
      respectively. We conclude that caspase 3-mediated removal of the CCTalpha NLS
      contributes minimally to the inhibition of PtdCho synthesis during DNA damage
      induced apoptosis. Rather, the CDP-choline pathway is inhibited by caspase 3
      independent and -dependent suppression of choline transport into cells.

PMID- 24136824
TI  - Docosahexaenoic acid impairs the maturation of very low density lipoproteins in
      rat hepatic cells.
AB  - One mechanism of the lipid-lowering effects of the fish oil n-3 fatty acids
      [e.g., docosahexaenoic acid (DHA)] in cell and animal models is induced hepatic
      apolipoprotein B100 (apoB) presecretory degradation. This degradation occurs post
      endoplasmic reticulum, but whether DHA induces it before or after intracellular
      VLDL formation remains unanswered. We found in McA-RH7777 rat hepatic cells that
      DHA and oleic acid (OA) treatments allowed formation of pre-VLDL particles and
      their transport to the Golgi, but, in contrast to OA, with DHA pre-VLDL particles
      failed to quantitatively assemble into fully lipidated (mature) VLDL. This
      failure required lipid peroxidation and was accompanied by the formation of apoB
      aggregates (known to be degraded by autophagy). Preventing the exit of proteins
      from the Golgi blocked the aggregation of apoB but did not restore VLDL
      maturation, indicating that failure to fully lipidate apoB preceded its
      aggregation. ApoB autophagic degradation did not appear to require an
      intermediate step of cytosolic aggresome formation. Taken with other examples in
      the literature, the results of this study suggest that pre-VLDL particles that
      are competent to escape endoplasmic reticulum quality control mechanisms but fail
      to mature in the Golgi remain subject to quality control surveillance late in the
      secretory pathway. 

PMID- 24136826
TI  - Visual activity predicts auditory recovery from deafness after adult cochlear
      implantation.
AB  - Modern cochlear implantation technologies allow deaf patients to understand
      auditory speech; however, the implants deliver only a coarse auditory input and
      patients must use long-term adaptive processes to achieve coherent percepts. In
      adults with post-lingual deafness, the high progress of speech recovery is
      observed during the first year after cochlear implantation, but there is a large
      range of variability in the level of cochlear implant outcomes and the temporal
      evolution of recovery. It has been proposed that when profoundly deaf subjects
      receive a cochlear implant, the visual cross-modal reorganization of the brain is
      deleterious for auditory speech recovery. We tested this hypothesis in post
      lingually deaf adults by analysing whether brain activity shortly after
      implantation correlated with the level of auditory recovery 6 months later. Based
      on brain activity induced by a speech-processing task, we found strong positive
      correlations in areas outside the auditory cortex. The highest positive
      correlations were found in the occipital cortex involved in visual processing, as
      well as in the posterior-temporal cortex known for audio-visual integration. The
      other area, which positively correlated with auditory speech recovery, was
      localized in the left inferior frontal area known for speech processing. Our
      results demonstrate that the visual modality's functional level is related to the
      proficiency level of auditory recovery. Based on the positive correlation of
      visual activity with auditory speech recovery, we suggest that visual modality
      may facilitate the perception of the word's auditory counterpart in communicative
      situations. The link demonstrated between visual activity and auditory speech
      perception indicates that visuoauditory synergy is crucial for cross-modal
      plasticity and fostering speech-comprehension recovery in adult cochlear
      implanted deaf patients. 

PMID- 24136827
TI  - Regional perfusion by extracorporeal membrane oxygenation of abdominal organs
      from donors after circulatory death: a systematic review.
AB  - Organs from donors after circulatory death (DCDs) are particularly susceptible to
      the effects of warm ischemia injury. Regional perfusion (RP) by extracorporeal
      membrane oxygenation (ECMO) is increasingly being advocated as a useful remedy to
      the effects of ischemia/reperfusion injury, and it has been reported to enable
      the transplantation of organs from donors previously deemed unsuitable. The
      MEDLINE, Embase, and Cochrane databases were searched, and articles published
      between 1997 and 2013 were obtained. A systematic review was performed according
      to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Two hundred ten articles were identified, and 11 were eligible for
      inclusion. Four hundred eighty-two kidneys and 79 livers were transplanted from
      regional perfusion-supported donor after circulatory death (RP-DCD) sources. One
      year graft survival was lower with uncontrolled RP-DCD liver transplantation,
      whereas 1-year patient survival was similar. Primary nonfunction and ischemic
      cholangiopathy were significantly more frequent with RP-DCDs versus donors after
      brain death (DBDs), but there was no difference in postoperative mortality
      between the 2 groups. The 1-year patient and graft survival rates for RP-DCD
      kidney transplantation were better than the rates with standard DCDs and were
      comparable to, if not better than, the rates with DBDs. At experienced centers,
      delayed graft function (DGF) for kidney transplantation from RP-DCDs was much
      less frequent in comparison with all other donor types. In conclusion, RP aids
      the recovery of DCD organs from ischemic injury and enables transplantation with
      acceptable survival. RP may help to increase the donor pool, but its benefits
      must still be balanced with the recognition of significantly higher rates of
      complications in liver transplantation. In kidney transplantation, significant
      reductions in DGF can be obtained with RP, and there are potentially important
      implications for long-term outcomes. Significant ethicolegal issues exist, and
      they are preventing a worldwide consensus on optimum RP protocols and an accurate
      appreciation of outcomes.

PMID- 24136825
TI  - Cell number changes in Alzheimer's disease relate to dementia, not to plaques and
      tangles.
AB  - Alzheimer's disease is the commonest cause of dementia in the elderly, but its
      pathological determinants are still debated. Amyloid-beta plaques and
      neurofibrillary tangles have been implicated either directly as disruptors of
      neural function, or indirectly by precipitating neuronal death and thus causing a
      reduction in neuronal number. Alternatively, the initial cognitive decline has
      been attributed to subtle intracellular events caused by amyloid-beta oligomers,
      resulting in dementia after massive synaptic dysfunction followed by neuronal
      degeneration and death. To investigate whether Alzheimer's disease is associated
      with changes in the absolute cell numbers of ageing brains, we used the isotropic
      fractionator, a novel technique designed to determine the absolute cellular
      composition of brain regions. We investigated whether plaques and tangles are
      associated with neuronal loss, or whether it is dementia that relates to changes
      of absolute cell composition, by comparing cell numbers in brains of patients
      severely demented with those of asymptomatic individuals-both groups
      histopathologically diagnosed as Alzheimer's-and normal subjects with no
      pathological signs of the disease. We found a great reduction of neuronal numbers
      in the hippocampus and cerebral cortex of demented patients with Alzheimer's
      disease, but not in asymptomatic subjects with Alzheimer's disease. We concluded
      that neuronal loss is associated with dementia and not the presence of plaques
      and tangles, which may explain why subjects with histopathological features of
      Alzheimer's disease can be asymptomatic; and exclude amyloid-beta deposits as
      causes for the reduction of neuronal numbers in the brain. We found an increase
      of non-neuronal cell numbers in the cerebral cortex and subcortical white matter
      of demented patients with Alzheimer's disease when compared with asymptomatic
      subjects with Alzheimer's disease and control subjects, suggesting a reactive
      glial cell response in the former that may be related to the symptoms they
      present. 

PMID- 24136828
TI  - Unzipping nucleoside channels by means of alcohol disassembly.
AB  - Gold nanoparticles capped with simple adenosine derivatives can form colloidal
      aggregates in nonpolar solvents. Theoretical calculations indicate the formation
      of organic channels by the supramolecular assembly of the nanoparticles by means
      of hydrogen bonds between the adenine moieties. The aggregates were only
      negligibly sensitive to nPrOH, iPrOH, and tBuOH, whereas some showed a similar
      response to MeOH and EtOH, and others showed high selectivity toward MeOH. DNA
      nucleoside derivatives (1-(2-deoxy-beta-D-ribofuranosyl)-5-methyluracil and 2',3'
      O-isopropylideneadenosine) as well as thymine and other aromatic compounds such
      as pyrene derivatives (pyrene, 1-chloropyrene, 1-hydroxypyrene, (1
      pyrenyl)methanol, and 2-hydroxynapthalene) did not induce disassembly of the
      nanoparticle aggregates. Data suggest that the nucleoside channels allow access
      to alcohols according to their size, and an efficient interaction between the
      alcohol and the adenine units destabilizes the hydrogen bonds, which eventually
      leads to nanoparticle disassembly. 

PMID- 24136829
TI  - Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions:
      findings on MRI and computed tomography imaging.
AB  - PURPOSE: To retrospectively analyze MRI and computed tomographic (CT) findings
      from renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions
      (Xp11-RCC). MATERIALS AND METHODS: Institutional review board permission was
      obtained to review patient medical records, and the requirement for informed
      consent was waved . The clinical and MRI/CT features of five cases with Xp11-RCC
      that were confirmed by pathology were analyzed retrospectively. The image
      characteristics included the lesion location and size, contribution of cystic and
      solid components, intratumoral necrosis or hemorrhage, invasion of perinephric
      tissue and renal sinus, lymphadenopathy, major venous or arterial vascular
      invasion, pattern of the tumor growth, intratumor calcification and lipids,
      homogeneity of SI on T2-weighted images, attenuation and SI of the mass with
      respect to the normal renal cortex on precontrast and contrasted CT/MRI images,
      tumor SIs, tumor attenuations and tumor-to-cortex indices, homogeneity of
      enhancement on the contrasted images. RESULTS: The mean age was 32 years (range,
      15-47 years). Most patients (4/5) were women. All tumors showed a cortical
      location. The average tumor size was 9 cm (range, 4-18 cm). Four tumors comprised
      a predominantly solid lesion with focal necrosis, and one tumor comprised a solid
      lesion with significant necrosis. All tumors showed intertumor hemorrhage,
      infiltrative growth and invasion of the perirenal adipose/renal sinus. Four cases
      showed retroperitoneal lymphadenopathy, of which one case showed simultaneous
      mediastinal and supraclavicular lymphadenopathy. All tumors from four cases
      showed mild hyperintensity on T1-weighted MRI images, and three tumors showed
      hypointensity on T2-weighted MRI images relative to the renal cortex except for 1
      tumor that showed significant hemorrhage and a relative hyperintensity. For 3
      cases who were imaged with CT, two tumors imaged using nonenhanced CT images
      showed mild hyperdensity relative to the renal cortex. Calcification was noted in
      all three tumors. All tumors showed mild, persistent enhancement. CONCLUSION:
      Typical Xp11-RCC manifests as an advanced, solid renal mass with mild persistent
      enhancement, a prevalence of intertumor hemorrhage/calcification, and a cortical
      epicenter location. The predilection for children and young adults is a useful
      clinical feature when confirming a diagnosis of Xp11-RCC.

PMID- 24136830
TI  - Superhydrogels of nanotubes capable of capturing heavy-metal ions.
AB  - Self-assembly regulated by hydrogen bonds was successfully achieved in the system
      of lithocholic acid (LCA) mixed with three organic amines, ethanolamine (EA),
      diethanolamine (DEA), and triethanolamine (TEA), in aqueous solutions. The
      mixtures of DEA/LCA exhibit supergelation capability and the hydrogels consist of
      plenty of network nanotubes with uniform diameters of about 60 nm determined by
      cryogenic TEM. Interestingly, the sample with the same concentration in a system
      of EA and LCA is a birefringent solution, in which spherical vesicles and can be
      transformed into nanotubes as the amount of LCA increases. The formation of
      hydrogels could be driven by the delicate balance of diverse noncovalent
      interactions, including electrostatic interactions, hydrophobic interactions,
      steric effects, van der Waals forces, and mainly hydrogen bonds. The mechanism of
      self-assembly from spherical bilayer vesicles into nanotubes was proposed. The
      dried hydrogels with nanotubes were explored to exhibit the excellent capability
      for capturing heavy-metal ions, for example, Cu(2+), Co(2+), Ni(2+), Pb(2+), and
      Hg(2+). The superhydrogels of nanotubes from the self-assembly of low-molecular
      weight gelators mainly regulated by hydrogen bonds used for the removal of heavy
      metal ions is simple, green, and high efficiency, and provide a strategic
      approach to removing heavy-metal ions from industrial sewage.

PMID- 24136831
TI  - Optically transparent water oxidation catalysts based on copper nanowires.
AB  - Let the light shine through: A transparent film of copper nanowires was
      transformed into an electrocatalyst for water oxidation by electrodepostion of Ni
      or Co onto the surface of the nanowires. These core-shell nanowire networks
      exhibit electrocatalytic performance equivalent to metal oxide films of similar
      composition, but are several times more transparent. 

PMID- 24136832
TI  - Youth service organizations.

PMID- 24136834
TI  - Proem.

PMID- 24136835
TI  - Better practice in working directly with youth. Preface.

PMID- 24136836
TI  - Missing in the youth development literature: the organization as host, cage, and
      promise.
AB  - Good, high-quality youth development programs require effective youth
      organizations. While youth organizations are commonly understood as valuable and
      supportive of healthy youth development, attention and focus on youth
      organizations in both scholarship and practice are missing within the youth
      development field. The authors advocate for a more distinct and clearer focus on
      youth organizations to foster positive youth development. 

PMID- 24136837
TI  - From youth worker professional development to organizational change.
AB  - An ongoing, innovative youth worker professional development is described in this
      article. This initiative began as youth worker professional development and then
      transcended to personal and organizational development. It grew from a moral
      response of Saint Paul Parks and Recreation staff and two faculty members of
      Youth Studies, University of Minnesota to offer higher-quality services to youth
      for their healthy development. Its underlying philosophies and ethos included
      building and sustaining meaningful relationships, cocreating a space for learning
      and change, becoming a reflecting practitioner, and community organizing. This
      professional development responded to the participants' interests and needs or to
      local situations in that moment, that space, and the discussions, and took on
      different shapes at different times. There were many accomplishments of,
      challenges and barriers to, and lessons learned from this professional
      development. 

PMID- 24136838
TI  - Use of research for transforming youth agencies.
AB  - Current philosophy and practice urge, even require for funding, that programs be
      empirically based and grounded in empirically proven emerging, promising, or best
      practices. In most of the human services, including youth programs, services, and
      practices, this requirement is a goal as well as an ideal. Empirical research and
      evaluation can be used in many ways. This article describes how it can be used
      for problem construction, a sociopolitical process that intentionally transforms
      data into "problems," the latter to mobilize and respond to the conditions
      documented in and by the data. This is the research strategy used primarily in an
      effort to transform a community youth service agency. 

PMID- 24136839
TI  - Youth advisory structures: listening to young people to support quality youth
      services.
AB  - Creating structures to include young people's opinions and advice has been
      recognized as important for high-quality youth programs and services. Recent
      scholarship has begun to learn that most of these efforts are often symbolic
      rather than substantive. While continually advocated for, the practice is not
      widespread or well done. Using data from a statewide study of youth advisory
      structures and a case study of one advisory structure used within a municipal
      parks and recreation center, this article describes what both of these teach
      about creating substantive, meaningful, and useful youth advisory structure for
      program and organization development. 

PMID- 24136840
TI  - Shaping partnerships by doing the work.
AB  - Partnership as an ordinary, everyday way of doing business within Saint Paul
      Parks and Recreation (P&R) has often been limited to working with individuals,
      groups, or agencies through a contract, generally to provide fee-based programs
      or services. This approach does not encourage new ways of thinking about or
      working with other organizations on a common purpose or service. Other
      partnership approaches are necessary to bring innovation to this work. These must
      allow and foster space for joint negotiation, for ways to meet needs and wants of
      both organizations and their missions, and focus on meeting community needs. 

PMID- 24136841
TI  - What can local foundations do to support youth service system change efforts?
AB  - Making sound decisions in funding youth-serving organizations can be greatly
      enhanced by implementing a comprehensive and inclusive learning process that
      embraces the perspectives of and input from a variety of stakeholders, including
      program staff and leadership, various community partners, and, most important,
      the youth. Youthprise effectively applied this collaborative approach to its
      grant making in 2012 when it funded Saint Paul Parks and Recreation (P&R) to
      continue and expand its innovations in youth work and diffuse specific strategies
      into other recreation centers. For a new grant-making intermediary, this was an
      ideal opportunity to test its priorities with an organization that had a
      demonstrated commitment to working with young people who were severely
      marginalized by other youth-serving agencies. Youthprise's relationship with P&R
      has yielded valuable insight that has informed its work as a grant maker and as
      an organization focused on systems change. 

PMID- 24136842
TI  - From lessons learned to emerging practices.
AB  - Organizational development is based in part on knowledge development, both
      formal, scientifically proven and also nonscientific practice wisdom. This
      article brings together all of the lessons learned over our six years of work
      with Saint Paul Parks and Recreation, and suggests the practice utility of these.

PMID- 24136843
TI  - Spatial visualization ability and laparoscopic skills in novice learners:
      evaluating stereoscopic versus monoscopic visualizations.
AB  - Elevated spatial visualization ability (Vz) is thought to influence surgical
      skill acquisition and performance. Current research suggests that stereo
      visualization technology and its association with skill performance may confer
      perceptual advantages. This is of particular interest in laparoscopic skill
      training, where stereo visualization may confer learning advantages to novices of
      variant Vz. This study explored laparoscopic skill performance scores in novices
      with variable spatial ability utilizing stereoscopic and traditional monoscopic
      visualization paradigms. Utilizing the McGill Inanimate System for Teaching and
      Evaluating Laparoscopic Skills (MISTELS) scoring protocol it was hypothesized
      that individuals with high spatial visualization ability (HVz) would achieve
      higher overall and individual MISTELS task scores as compared to low spatial
      visualization ability (LVz) counterparts. Further, we also hypothesized that a
      difference would exist between HVz and LVz individual scores based on the viewing
      modality employed. No significant difference was observed between HVz and LVz
      individuals for MISTELS tasks scores, overall or individually under both viewing
      modalities, despite higher average MISTELS scores for HVz individuals. The lack
      of difference between scores obtained under the stereo modality suggested that
      the additional depth that is conferred by the stereoscopic visualization may act
      to enhance performance for individuals with LVz, potentially equilibrating their
      performance with their HVz peers. Further experimentation is required to better
      ascertain the effects of stereo visualization in individuals of high and low Vz,
      though it appears stereoscopic visualizations could serve as a prosthetic to
      enhance skill performance.

PMID- 24136844
TI  - Genome Sequences of Listeria monocytogenes Serotype 4b Variant Strains Isolated
      from Clinical and Environmental Sources.
AB  - Listeria monocytogenes strains that show a novel PCR serotyping profile (IVb-v1)
      have been reported recently. Here, we announce the draft genome sequences of five
      L. monocytogenes IVb-v1 strains isolated from the United States and Australia
      that harbor a 6.3-kb DNA cassette characteristic of serotype 1/2a strains. 

PMID- 24136845
TI  - Draft Genome Sequences of Pseudomonas aeruginosa B3 Strains Isolated from a
      Cystic Fibrosis Patient Undergoing Antibiotic Chemotherapy.
AB  - Pseudomonas aeruginosa frequently establishes chronic infections in the airways
      of patients suffering from cystic fibrosis (CF). Here, we report the draft genome
      sequences of four P. aeruginosa B3 strains isolated from a chronically infected
      CF patient undergoing antibiotic chemotherapy. 

PMID- 24136846
TI  - Genome Sequences of Salmonella enterica Serotype Typhimurium Blood Clinical
      Isolate ST4848/06 and Stool Isolate ST1489/06.
AB  - Salmonella enterica serotype Typhimurium human blood strains isolated from
      outside Africa are rarely sequenced. Here, we report the draft genome sequences
      of two S. Typhimurium clinical strains isolated in the same year, one from blood
      and another from stool, in order to gain insights into the genetic basis leading
      to invasive diseases. 

PMID- 24136847
TI  - Draft Genome Sequence of the Dimorphic Prosthecate Bacterium Brevundimonas
      abyssalis TAR-001T.
AB  - We report the 3.0-Mb draft genome sequence of Brevundimonas abyssalis strain TAR
      001(T), isolated from deep-sea floor sediment. The draft genome sequence of
      strain TAR-001(T) consists of 2,979,700 bp in 128 contigs, with a G+C content of
      68.2%, 2,946 potential coding sequences (CDS), 3 rRNAs, and 41 tRNAs. 

PMID- 24136848
TI  - Genome Sequence Analysis of Staphylococcus equorum Bovine Mastitis Isolate UMC
      CNS-924.
AB  - Intramammary infections in dairy cattle are frequently caused by staphylococci,
      resulting in mastitis and associated economic losses. A draft genome sequence was
      determined for Staphylococcus equorum UMC-CNS-924, isolated from the milk of a
      Holstein cow, to better understand the genetic basis of its pathogenesis and
      adaptation to the bovine mammary gland. 

PMID- 24136849
TI  - Draft Genome Sequences of Burkholderia cenocepacia ET12 Lineage Strains K56-2 and
      BC7.
AB  - The Burkholderia cepacia complex (BCC) is a group of closely related bacteria
      that are responsible for respiratory infections in immunocompromised humans, most
      notably those with cystic fibrosis (CF). We report the genome sequences for
      Burkholderia cenocepacia ET12 lineage CF isolates K56-2 and BC7. 

PMID- 24136850
TI  - Draft Genome Sequence of Rhodococcus erythropolis DN1, a Crude Oil Biodegrader.
AB  - We report the 6,548-Mb genome sequence of Rhodococcus erythropolis strain DN1,
      isolated from the oil-contaminated soil in the Karagandy region of Kazakhstan.
      The draft genome sequence of strain DN1 might provide new insights into the
      genetic mechanisms of crude oil biodegradation. 

PMID- 24136851
TI  - Genome Sequences of Mannheimia haemolytica Serotype A1 Strains D153 and D193 from
      Bovine Pneumonia.
AB  - Here we report two genome sequences, one complete and one draft, from virulent
      bovine strains of Mannheimia haemolytica serotype A1 recovered prior to the field
      usage of modern antimicrobial drugs. 

PMID- 24136852
TI  - Draft Genome Sequence of the Extremely Halophilic Bacillus sp. Strain SB49,
      Isolated from a Salt Crystallizer Pond of the Little Rann of Kutch, India.
AB  - Here we report the draft whole-genome sequence (3.72 Mbp) of Bacillus sp. strain
      SB49, an extremely halophilic bacterium isolated from a salt crystallizer pond of
      the Little Rann of Kutch in India. Unraveling the genome of this organism will
      facilitate understanding and isolation of the genes involved in imparting extreme
      osmotolerance. 

PMID- 24136853
TI  - Draft Genome Sequence of the Hydrogen- and Ethanol-Producing Bacterium
      Clostridium intestinale Strain URNW.
AB  - Here, we report the draft genome sequence of Clostridium intestinale strain URNW,
      which can convert biomass to useful products such as biofuels (hydrogen or
      ethanol) and other soluble end products. 

PMID- 24136854
TI  - Draft Genome Sequence of Pasteurella multocida subsp. multocida Strain PMTB,
      Isolated from a Buffalo.
AB  - Pasteurella multocida serotypes B:2 and E:2 are the main causative agents of
      ruminant hemorrhagic septicemia in Asia and Africa, respectively. Pasteurella
      multocida strain PMTB was isolated from a buffalo with hemorrhagic septicemia and
      has been determined to be serotype B:2. Here we report the draft genome sequence
      of strain PMTB. 

PMID- 24136855
TI  - Variable selection on large case-crossover data: application to a registry-based
      study of prescription drugs and road traffic crashes.
AB  - PURPOSE: In exploratory analyses of pharmacoepidemiological data from large
      populations with large number of exposures, both a conceptual and computational
      problem is how to screen hypotheses using probabilistic reasoning, selecting drug
      classes or individual drugs that most warrant further hypothesis testing.
      METHODS: We report the use of a shrinkage technique, the Lasso, in the
      exploratory analysis of the data on prescription drugs and road traffic crashes,
      resulting from the case-crossover matched-pair interval approach described by
      Orriols and colleagues (PLoS Med 2010; 7:e1000366). To prevent false-positive
      results, we consider a bootstrap-enhanced version of the Lasso. To highlight the
      most stable results, we extensively examine sensitivity to the choice of referent
      window. RESULTS: Antiepileptics, benzodiazepine hypnotics, anxiolytics,
      antidepressants, antithrombotic agents, mineral supplements, drugs used in
      diabetes, antiparkinsonian treatment, and several cardiovascular drugs showed
      suspected associations with road traffic accident involvement or accident
      responsibility. CONCLUSION: These results, in relation to other findings in the
      literature, provide new insight and may generate new hypotheses on the
      association between prescription drugs use and impaired driving ability.

PMID- 24136856
TI  - Water-dependent optical activity inversion of chiral DNA-silica assemblies.
AB  - Chirality is widely found in nature and is expressed hierarchically in many
      organic-inorganic hybrid materials. Optical activity (OA) is the most fundamental
      attribute of these chiral materials. In this study, we found that the OA of
      impeller-like chiral DNA-silica assemblies (CDSAs) was inverted with the addition
      of water. The state of DNA under dry and wet conditions, and the dual chirality
      of chiral DNA layers and twisted helical arrays of opposite handedness in CDSAs
      were considered to exert predominant effects on the OAs. The circular dichroism
      (CD) responses for the dry CDSAs were mostly attributed to the chiral arrangement
      of DNA layers, whereas the opposite CD responses for the wet CDSAs primarily
      originated from twisted helical arrays of DNA molecules. The observed CD signals
      were a super-position of the two opposing OA responses. The increase in the
      longitudinal relation of DNA molecules due to the recovery of a double-helical
      structure of DNA in the presence of water was considered to be the reason for the
      increase in intensity of the CD signals that originated from the twisted helical
      array, which led to the inversion of OA of the CDSAs. The inversion of the
      plasmon-resonance-based OAs for the chiral-arranged achiral Ag nanoparticles
      (NPs) located in the channels of the CDSAs in dry and wet states further
      confirmed the dual chirality of DNA packing. Such research on DNA assemblies and
      metal NPs with dual, opposite chirality assists in the understanding of DNA
      hierarchical chirality in living systems and the creation of macroscopic ordered
      helical materials and biosensors. 

PMID- 24136857
TI  - A synthetic small molecule for targeted transcriptional activation of germ cell
      genes in a human somatic cell.

PMID- 24136858
TI  - Solution-processable n-type semiconductors based on unsymmetrical naphthalene
      imides: synthesis, characterization, and applications in field-effect
      transistors.
AB  - A series of unsymmetrical naphthalene imide derivatives (1-5) with high electron
      affinity was synthesized and used in n-channel organic field-effect transistors
      (OFETs). They have very good solubility in common organic solvents and good
      thermal stability up to 320  degrees C. Their photophysical, electrochemical, and
      thermal properties were investigated in detail. They showed low-lying LUMO energy
      levels from -3.90 to -4.15 eV owing to a strong electron-withdrawing character.
      Solution-processed thin-film OFETs based on 1-4 were measured in both N2 and air.
      They all showed n-type FET behavior. The liquid-crystalline compounds 1a, 1b, and
      3 showed good performance owing to the self-healing properties of the film in the
      liquid-crystal phase. Compound 3 has an electron mobility of up to 0.016 cm(2)V(
      1) s(-1) and current on/off ratios of 10(4)-10(5).

PMID- 24136859
TI  - Injuries among Spanish male amateur soccer players: a retrospective population
      study.
AB  - BACKGROUND: Soccer is the most popular sport worldwide, with about 265 million
      players, both professionals and amateurs. Most research investigating soccer
      injuries has focused on professional players because they have greater exposure
      time, but most soccer players are at the recreational level. PURPOSE: To
      undertake a retrospective epidemiological study of the injuries sustained in
      Spanish amateur soccer during the 2010-2011 season. STUDY DESIGN: Descriptive
      epidemiological study. METHODS: Any injuries incurred by the 134,570 recreational
      soccer players (aged 18-55 years) registered with the Spanish Football Federation
      were reported to the federation's medical staff. A standardized medical
      questionnaire, based on the Federation International de Football Association
      (FIFA) Medical and Research Centre (F-MARC) consensus for collection procedures
      in studies of soccer injuries, was used to classify the injury according to type,
      severity, location, and treatment. RESULTS: A total of 15,243 injuries were
      reported, with an average of 0.11 injuries per player and per year. From the
      total number of injuries, 67.2% were classified as injuries that resulted in time
      loss, while the remaining 32.7% were injuries that required medical attention.
      Most injuries led to a minimum of 1 competitive match being missed (87%), and
      only 2.5% were recurrent injuries. The rate of injuries per 1000 hours of play
      was double during games (1.15/1000 hours) compared with during training
      (0.49/1000 hours). From the total number of injuries reported, 7.7% corresponded
      to goalkeepers, 24.2% to forwards, 33.8% to defenders, and 34.3% to midfielders.
      The knee (29.9%) and ankle joints (12.4%) were the most common body locations
      injured, while ligament sprains and ruptures accounted for 32.1% of the total
      injuries attended. Older amateur players (age >=30 years) had a greater number of
      injuries per year and per 1000 hours of play than their younger counterparts.
      CONCLUSION: The risk of injury in amateur soccer is lower than that previously
      reported in professional players. The most common complaints in amateur players
      are knee ligament injuries. Further research is needed to investigate ways of
      reducing the incidence of injuries in amateur soccer.

PMID- 24136860
TI  - Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma
      decrease collagen gene synthesis in tendons.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is used for the treatment of tendinopathy.
      There are numerous PRP preparations, and the optimal combination of platelets and
      leukocytes is not known. HYPOTHESIS: Within leukocyte-reduced PRP (lrPRP), there
      is a plateau effect of platelet concentration, with increasing platelet
      concentrations being detrimental to extracellular matrix synthesis. STUDY DESIGN:
      Controlled laboratory study. METHODS: Different formulations of lrPRP with
      respect to the platelet:leukocyte ratio were generated from venous blood of 8
      horses. Explants of the superficial digital flexor tendon were cultured in lrPRP
      products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor
      necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1),
      and interleukin-1beta (IL-1beta) concentrations were determined in the media by
      enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen
      type I and III (COL1A1 and COL3A1, respectively), matrix metalloproteinase-3 and 
      13 (MMP-3 and MMP-13, respectively), cartilage oligomeric matrix protein (COMP),
      and IL-1beta was determined. Data were divided into 3 groups of lrPRP based on
      the ratio of platelets:leukocytes and evaluated to determine the effect of
      platelet concentration. RESULTS: Complete blood counts verified leukocyte
      reduction and platelet enrichment in all PRP preparations. In the lrPRP
      preparation, the anabolic growth factors PDGF-BB and TGF-beta1 were increased
      with increasing platelet concentrations, and the catabolic cytokine IL-1beta was
      decreased with increasing platelet concentrations. Increasing the platelet
      concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis
      in tendons. CONCLUSION: Increasing the platelet concentration within lrPRP
      preparations results in the delivery of more anabolic growth factors and less
      proinflammatory cytokines, but the biological effect on tendons is diminished
      metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1.
      Together, this information suggests that minimizing leukocytes in PRP is more
      important than maximizing platelet numbers with respect to decreasing
      inflammation and enhancing matrix gene synthesis. CLINICAL RELEVANCE: This study
      suggests that reducing leukocytes to minimize catabolic signaling appears to be
      more important than increasing platelets in an effort to maximize anabolic
      signaling. Further, a maximum biological threshold of benefit was demonstrated
      with regard to the number of platelets beyond which further increases in platelet
      concentration did not result in further anabolic upregulation. In vivo
      investigations documenting the use of platelets for the treatment of tendinopathy
      are justified as well as further in vitro characterization of the ideal PRP
      product for the treatment of tendinopathy and other musculoskeletal applications.

PMID- 24136861
TI  - Paralogue annotation identifies novel pathogenic variants in patients with
      Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia.
AB  - BACKGROUND: Distinguishing genetic variants that cause disease from variants that
      are rare but benign is one of the principal challenges in contemporary clinical
      genetics, particularly as variants are identified at a pace exceeding the
      capacity of researchers to characterise them functionally. METHODS: We previously
      developed a novel method, called paralogue annotation, which accurately and
      specifically identifies disease-causing missense variants by transferring disease
      causing annotations across families of related proteins. Here we refine our
      approach, and apply it to novel variants found in 2266 patients across two large
      cohorts with inherited sudden death syndromes, namely catecholaminergic
      polymorphic ventricular tachycardia (CPVT) or Brugada syndrome (BrS). RESULTS:
      Over one third of the novel non-synonymous variants found in these studies, which
      would otherwise be reported in a clinical diagnostics setting as 'variants of
      unknown significance', are categorised by our method as likely disease causing
      (positive predictive value 98.7%). This identified more than 500 new disease loci
      for BrS and CPVT. CONCLUSIONS: Our methodology is widely transferable across all
      human disease genes, with an estimated 150 000 potentially informative
      annotations in more than 1800 genes. We have developed a web resource that allows
      researchers and clinicians to annotate variants found in individuals with
      inherited arrhythmias, comprising a referenced compendium of known missense
      variants in these genes together with a user-friendly implementation of our
      approach. This tool will facilitate the interpretation of many novel variants
      that might otherwise remain unclassified.

PMID- 24136862
TI  - A novel heterozygous OPA3 mutation located in the mitochondrial target sequence
      results in altered steady-state levels and fragmented mitochondrial network.
AB  - BACKGROUND: Mutations in OPA3 have been reported in patients with autosomal
      dominant optic atrophy plus cataract and Costeff syndrome. Here, we report the
      results of a comprehensive study on OPA3 mutations, including the mutation
      spectrum and its prevalence in a large cohort of OPA1-negative autosomal dominant
      optic atrophy (ADOA) patients, the associated clinical phenotype and the
      functional characterisation of a newly identified OPA3 mutant. METHODS: Mutation
      analysis was carried out in a patient cohort of 121 independent ADOA patients. To
      characterise a novel OPA3 mutation, we analysed the mitochondrial import, steady
      state levels and the mitochondrial localisation of the mutated protein in
      patients' fibroblasts. Furthermore, the morphology of mitochondria harbouring the
      mutated OPA3 was monitored. RESULTS: We identified four independent cases
      (representing families with multiple affected members) with OPA3 mutations.
      Besides the known p.Q105E mutation, we observed a novel insertion,
      c.10_11insCGCCCG/p.V3_G4insAP which is located in the mitochondrial presequence.
      Detailed functional analysis of mitochondria harbouring this novel mutation
      demonstrates a fragmented mitochondrial network with a decreased mitochondrial
      mass in patient fibroblasts. In addition, quantification of the OPA3 protein
      reveals decreased steady-state levels of the mutant protein compared with the
      native one. Comparison of the clinical phenotypes suggests that OPA3 mutations
      can additionally evoke hearing loss and by that extend the clinical manifestation
      of OPA3-associated optic atrophy. This finding is supported by expression
      analysis of OPA3 in murine cochlear tissue. CONCLUSIONS: In summary, our study
      provides new insights into the clinical spectrum and the pathogenesis of dominant
      optic atrophy caused by mutations in the OPA3 gene.

PMID- 24136863
TI  - Thoracic inlet or thoracic outlet: which one is which in anatomical and clinical
      literature?

PMID- 24136864
TI  - Evidence of a chemopreventive effect of progestin unrelated to ovulation on
      reproductive tract cancers in the egg-laying hen.
AB  - Epidemiologic, laboratory, and animal evidence suggests that progestins and
      vitamin D may be potent ovarian cancer preventives. Our objectives were to
      evaluate progestins as reproductive tract cancer chemopreventives in the chicken,
      determine whether restricted ovulation affected the incidence of reproductive
      tract tumors, and assess whether vitamin D would confer cancer protection either
      alone or in addition to progestin. A total of 2,400 two-year-old Single Comb
      White Leghorns were randomized into six groups (400 each) with hormonal and
      dietary manipulation for 2 years as follows: (i) no intervention, regular
      feed/caloric intake, (ii) control, (iii) vitamin D, (iv) the progestin
      levonorgestrel, (v) vitamin D plus levonorgestrel, and (vi) the progestin Provera
      (medroxyprogesterone acetate). Groups 2 to 6 were caloric restricted to inhibit
      ovulation. Our results indicated that caloric restriction decreased egg
      production by more than 60%, and was associated with a greater than 70% decrease
      in reproductive tract cancers. Ovulatory events did not differ among the caloric
      restricted groups (groups 2-6), except for the group receiving levonorgestrel,
      which had fewer ovulatory events than controls (P = 0.046). After correcting for
      egg production, birds receiving progestins had significantly fewer reproductive
      tract cancers [OR, 0.61; confidence interval (CI), 0.39-0.95; P = 0.03], with
      similar proportionate reductions in tumors arising in either the ovary or
      oviduct. Vitamin D did not significantly affect cancer incidence overall, or add
      to the cancer preventive effect of progestins. This study suggests a protective
      effect of progestins against ovarian and oviductal cancers. These data support
      the concept that progestins provide a chemopreventive effect unrelated to
      ovulation.

PMID- 24136865
TI  - Thiophosphoramide-based cooperative catalysts for Bronsted acid promoted ionic
      Diels-Alder reactions.

PMID- 24136866
TI  - Ionic liquid propellants: future fuels for space propulsion.
AB  - Use of green propellants is a trend for future space propulsion. Hypergolic ionic
      liquid propellants, which are environmentally-benign while exhibiting energetic
      performances comparable to hydrazine, have shown great potential to meet the
      requirements of developing nontoxic high-performance propellant formulations for
      space propulsion applications. This Concept article presents a review of recent
      advances in the field of ionic liquid propellants. 

PMID- 24136867
TI  - Time discounting and smoking behavior: evidence from a panel survey(*).
AB  - By using a panel survey of Japanese adults, we show that smoking behavior is
      associated with personal time discounting and its biases, such as hyperbolic
      discounting and the sign effect, in the way that theory predicts: smoking depends
      positively on the discount rate and the degree of hyperbolic discounting and
      negatively on the presence of the sign effect. Positive effects of hyperbolic
      discounting on smoking are salient for naive people, who are not aware of their
      self-control problem. By estimating smoking participation and smokers' cigarette
      consumption in Cragg's two-part model, we find that the two smoking decisions
      depend on different sets of time-discounting variables. Particularly, smoking
      participation is affected by being a naive hyperbolic discounter, whereas the
      discount rate, the presence of the sign effect, and a hyperbolic discounting
      proxy constructed from procrastination behavior vis-a-vis doing homework
      assignments affect both types of decision making. The panel data enable us to
      analyze the over-time instability of elicited discount rates. The instability is
      shown to come from measurement errors, rather than preference shocks on time
      preference. Several evidences indicate that the detected associations between
      time preferences and smoking behavior are interpersonal one, rather than within
      personal one.

PMID- 24136868
TI  - Adjusting overall survival for treatment switches: commonly used methods and
      practical application.
AB  - In parallel group trials, long-term efficacy endpoints may be affected if some
      patients switch or cross over to the alternative treatment arm prior to the
      event. In oncology trials, switch to the experimental treatment can occur in the
      control arm following disease progression and potentially impact overall
      survival. It may be a clinically relevant question to estimate the efficacy that
      would have been observed if no patients had switched, for example, to estimate
      'real-life' clinical effectiveness for a health technology assessment. Several
      commonly used statistical methods are available that try to adjust time-to-event
      data to account for treatment switching, ranging from naive exclusion and
      censoring approaches to more complex inverse probability of censoring weighting
      and rank-preserving structural failure time models. These are described, along
      with their key assumptions, strengths, and limitations. Best practice guidance is
      provided for both trial design and analysis when switching is anticipated.
      Available statistical software is summarized, and examples are provided of the
      application of these methods in health technology assessments of oncology trials.
      Key considerations include having a clearly articulated rationale and research
      question and a well-designed trial with sufficient good quality data collection
      to enable robust statistical analysis. No analysis method is universally suitable
      in all situations, and each makes strong untestable assumptions. There is a need
      for further research into new or improved techniques. This information should aid
      statisticians and their colleagues to improve the design and analysis of clinical
      trials where treatment switch is anticipated.

PMID- 24136869
TI  - Hydrophobic particle effects on hydrate crystal growth at the water-oil
      interface.
AB  - This study introduced hydrophobic silica nanoparticles (SiNPs) into an interface
      of aqueous and hydrate-forming oil phases and analyzed the inhibition of hydrate
      crystal growth after seeding the hydrate slurry. The hydrate inhibition
      performance was quantitatively identified by micro-differential scanning
      calorimetry (micro-DSC) experiments. Through the addition of 1.0 wt% of SiNPs
      into the water-oil interface, the hydrate crystal growth only occurred around the
      seeding position of cyclopentane (CP) hydrate slurry, and the growth of hydrate
      crystals was retarded. Upon a further increase in the SiNP concentration up to
      2.0 wt%, the SiNP-laden interface completely prevented hydrate growth. We
      observed a hollow conical shape of hydrate crystals with 0.0 and 1.0 wt% of
      SiNPs, respectively, but the size and shape of the conical crystals was shrunken
      at 1.0 wt% of silica nanoparticles. However, the conical shape did not appear
      with an increased nanoparticle concentration of 2 wt%. These findings can provide
      insight into hydrate inhibition in oil and gas delivery lines, possibly with
      nanoparticles.

PMID- 24136870
TI  - The McGurk effect in children with autism and Asperger syndrome.
AB  - Children with autism may have difficulties in audiovisual speech perception,
      which has been linked to speech perception and language development. However,
      little has been done to examine children with Asperger syndrome as a group on
      tasks assessing audiovisual speech perception, despite this group's often greater
      language skills. Samples of children with autism, Asperger syndrome, and Down
      syndrome, as well as a typically developing sample, were presented with an
      auditory-only condition, a speech-reading condition, and an audiovisual condition
      designed to elicit the McGurk effect. Children with autism demonstrated unimodal
      performance at the same level as the other groups, yet showed a lower rate of the
      McGurk effect compared with the Asperger, Down and typical samples. These results
      suggest that children with autism may have unique intermodal speech perception
      difficulties linked to their representations of speech sounds.

PMID- 24136871
TI  - Photosensitization of singlet oxygen and in vivo photodynamic therapeutic effects
      mediated by PEGylated W(18)O(49) nanowires.
AB  - Upon excitation with near-infrared light (980 nm), PEGylated W18 O49 nanowires
      can sensitize the formation of singlet oxygen and thus reactive oxygen species
      (ROS). The resulting photodynamic therapy (PDT) effect can cause the destruction
      of tumors in the absence of organic photosensitizers. PEG=poly(ethylene glycol),
      PTT=photothermal therapy. 

PMID- 24136872
TI  - European Federation of Statisticians in the Pharmaceutical Industry's position on
      access to clinical trial data.
AB  - The European Federation of Statisticians in the Pharmaceutical Industry (EFSPI)
      believes access to clinical trial data should be implemented in a way that
      supports good research, avoids misuse of such data, lies within the scope of the
      original informed consent and fully protects patient confidentiality. In
      principle, EFSPI supports responsible data sharing. EFSPI acknowledges it is in
      the interest of patients that their data are handled in a strictly confidential
      manner to avoid misuse under all possible circumstances. It is also in the
      interest of the altruistic nature of patients participating in trials that such
      data will be used for further development of science as much as possible applying
      good statistical principles. This paper summarises EFSPI's position on access to
      clinical trial data. The position was developed during the European Medicines
      Agency (EMA) advisory process and before the draft EMA policy on publication and
      access to clinical trial data was released for consultation; however, the EFSPI's
      position remains unchanged following the release of the draft policy. Finally,
      EFSPI supports a need for further guidance to be provided on important technical
      aspects relating to re-analyses and additional analyses of clinical trial data,
      for example, multiplicity, meta-analysis, subgroup analyses and publication bias.

PMID- 24136873
TI  - Bio-inspired formal synthesis of hirsutellones A-C featuring an electrophilic
      cyclization triggered by remote Lewis acid-activation.
AB  - A bio-inspired strategy was used to complete the formal synthesis of the
      antitubercular hirsutellone B and congeners A and C, through construction of its
      decahydrofluorene core from a linear polyene strand activated at both ends by a
      silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic
      cyclization, starting with the remote activation (by [Yb(OTf)3] or BF3.OEt2) of
      the allyl acetate and stereoselectively affording the C ring. This was followed
      by an intramolecular Diels-Alder reaction to get the tricyclic core of the
      natural product. The stereoselective reduction of the resulting ketone towards
      the formal intermediate was critical to the success of this strategy.

PMID- 24136874
TI  - Comparative analysis of pancreatic changes in aged rats fed life long with
      sunflower, fish, or olive oils.
AB  - An adequate pancreatic structure is necessary for optimal organ function.
      Structural changes are critical in the development of age-related pancreatic
      disorders. We aimed to study the effect of oil consumption on pancreas histology
      in order to find aging-related signs. To this end, three groups of rats were fed
      an isocaloric diet for 2 years, where virgin olive, sunflower, or fish oil was
      included. Pancreatic samples for microscopy and blood samples were collected at
      the moment of sacrifice. As a result, the sunflower oil-fed rats presented higher
      beta-cell numbers and twice the insulin content than virgin olive oil-fed
      animals. In addition, rats fed with fish oil developed acinar fibrosis and
      macrophage infiltrates in peri-insular regions, compared with counterparts fed
      with virgin olive oil. Inflammation signs were less prominent in the sunflower
      group. The obtained data emphasize the importance of dietary fatty acids in
      determining pancreatic structure. 

PMID- 24136875
TI  - Predictors of posttraumatic growth in women with breast cancer.
AB  - OBJECTIVE: Posttraumatic growth (PTG) is defined as 'positive psychological
      change experienced as a result of a struggle with highly challenging life
      circumstances'. The current study examined change in PTG over 2 years following
      breast cancer diagnosis and variables associated with PTG over time. METHODS:
      Women recently diagnosed with breast cancer completed surveys within 8 months of
      diagnosis and 6, 12, and 18 months later. Linear mixed effects models were used
      to assess the longitudinal effects of demographic, medical, and psychosocial
      variables on PTG as measured by the Posttraumatic Growth Inventory (PTGI).
      RESULTS: A total of 653 women were accrued (mean age = 54.9, SD = 12.6). Total
      PTGI score increased over time mostly within the first few months following
      diagnosis. In the longitudinal model, greater PTGI scores were associated with
      education level, longer time since diagnosis, greater baseline level of illness
      intrusiveness, and increases in social support, spirituality, use of active
      adaptive coping strategies, and mental health. Findings for the PTGI domains were
      similar to those for the total score except for the Spiritual Change domain.
      CONCLUSION: PTG develops relatively soon after a breast cancer diagnosis and is
      associated with baseline illness intrusiveness and increases in social support,
      spirituality, use of active-adaptive coping strategies, and mental health.

PMID- 24136876
TI  - Linking ethylene to nitrogen-dependent leaf longevity of grass species in a
      temperate steppe.
AB  - BACKGROUND AND AIMS: Leaf longevity is an important plant functional trait that
      often varies with soil nitrogen supply. Ethylene is a classical plant hormone
      involved in the control of senescence and abscission, but its role in nitrogen
      dependent leaf longevity is largely unknown. METHODS: Pot and field experiments
      were performed to examine the effects of nitrogen addition on leaf longevity and
      ethylene production in two dominant plant species, Agropyron cristatum and Stipa
      krylovii, in a temperate steppe in northern China. KEY RESULTS: Nitrogen addition
      increased leaf ethylene production and nitrogen concentration but shortened leaf
      longevity; the addition of cobalt chloride, an ethylene biosynthesis inhibitor,
      reduced leaf nitrogen concentration and increased leaf longevity. Path analysis
      indicated that nitrogen addition reduced leaf longevity mainly through altering
      leaf ethylene production. CONCLUSIONS: These findings provide the first
      experimental evidence in support of the involvement of ethylene in nitrogen
      induced decrease in leaf longevity.

PMID- 24136878
TI  - Preparation of a camptothecin prodrug with glutathione-responsive disulfide
      linker for anticancer drug delivery.
AB  - We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol
      monomethyl ether-block-poly(2-methacryl ester hydroxyethyl disulfide-graft-CPT)
      (MPEG-SS-PCPT). It formed biocompatible nanoparticles (NPs) with diameters of
      approximately 122 nm with a CPT loading content as high as approximately 25 wt%
      in aqueous solution. In in vitro release studies, these MPEG-SS-PCPT NPs could
      undergo triggered disassembly and much faster release of CPT under glutathione
      (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor
      activity, and another anticancer drug, doxorubicin hydrochloride (DOX?HCl), could
      also be introduced into the prodrug with a high loading amount. The DOX.HCl
      loaded CPT prodrug could deliver two anticancer drugs at the same time to produce
      a collaborative cytotoxicity toward cancer cells, which suggested that this GSH
      responsive NP system might become a promising carrier to improve drug-delivery
      efficacy.

PMID- 24136879
TI  - Enantioselective total synthesis of pinnaic acid and halichlorine.
AB  - The enantioselective total synthesis of the bioactive marine natural products
      pinnaic acid and halichlorine is reported in detail. Our total synthesis features
      the construction of the five-membered ring and C9 and C13 stereogenic centers
      through a palladium-catalyzed trimethylenemethane [3+2] cyclization; the
      installation of the nitrogen atom through a regioselective Beckmann rearrangement
      of a poorly reactive ketone; the stereoselective cyclization of the spiro ring
      through a four-step, one-pot hydrogenation-cyclization; and efficient connection
      of the sterically hindered lower chain through a reduced-pressure cross olefin
      metathesis reaction. 

PMID- 24136877
TI  - Auxin and the integration of environmental signals into plant root development.
AB  - BACKGROUND: Auxin is a versatile plant hormone with important roles in many
      essential physiological processes. In recent years, significant progress has been
      made towards understanding the roles of this hormone in plant growth and
      development. Recent evidence also points to a less well-known but equally
      important role for auxin as a mediator of environmental adaptation in plants.
      SCOPE: This review briefly discusses recent findings on how plants utilize auxin
      signalling and transport to modify their root system architecture when responding
      to diverse biotic and abiotic rhizosphere signals, including macro- and micro
      nutrient starvation, cold and water stress, soil acidity, pathogenic and
      beneficial microbes, nematodes and neighbouring plants. Stress-responsive
      transcription factors and microRNAs that modulate auxin- and environment-mediated
      root development are also briefly highlighted. CONCLUSIONS: The auxin pathway
      constitutes an essential component of the plant's biotic and abiotic stress
      tolerance mechanisms. Further understanding of the specific roles that auxin
      plays in environmental adaptation can ultimately lead to the development of crops
      better adapted to stressful environments.

PMID- 24136881
TI  - Directed evolution by using iterative saturation mutagenesis based on
      multiresidue sites.
AB  - Iterative saturation mutagenesis (ISM) in combination with reduced amino acid
      alphabets has been shown to be an efficient method for directed evolution. In
      order to minimize the screening effort, the number of residues in a given
      randomization site has thus far been restricted to two or three; this prevents
      oversampling from reaching astronomical numbers when 95 % library coverage is
      aimed for. In this study, ISM is applied for the first time by using
      randomization sites composed of five amino acid positions. The use of just two
      such sites (A and B) results in two different ISM pathways, A->B and B->A. A
      severely reduced amino acid alphabet (only five members) was employed for the
      building blocks-a minimal set of structurally representative amino acids. The
      Baeyer-Villiger monooxygenase PAMO was chosen as the enzyme for this proof-of
      principle study. The test system employed tuning of activity and
      diastereoselectivity in the oxidation of 4-(bromomethylidene)cyclohexanone, which
      is not accepted by wild-type PAMO. Although only 8-9 % library coverage was
      ensured (as calculated by traditional statistics), notable activity and 99 %
      diastereoselectivity were obtained, thus indicating that such an ISM strategy is
      viable in protein engineering.

PMID- 24136882
TI  - Depression, cytokines, and pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to examine the relationships between
      cytokines, depression, and pancreatic cancer. METHOD: A total of 75 individuals
      were recruited from two New York City hospitals (a cancer center and a
      psychiatric hospital) and composed of four subgroups: patients with
      adenocarcinoma of the pancreas who did (n = 17) and did not (n = 26) have a
      diagnosis of Major Depressive Episode (MDE), and healthy participants with (n =
      7) and without (n = 25) MDE. All individuals completed a battery of self-report
      measures. Sera was assayed using Meso Scale Discovery techniques to measure the
      following pro-inflammatory and anti-inflammatory cytokines: IL-1beta, IL-2, IL-3,
      IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-gamma, TGF-beta, and TNF-alpha; we also
      calculated the IL-2/IL-4 ratio. RESULTS: Pancreatic cancer patients had
      significantly higher levels of IL-6 and IL-10 and significantly lower TGF-beta
      levels than healthy participants. When the sample was divided into those with and
      without MDE, the groups only differed with regard to serum IL-6 levels. No
      significant cancer and depression interaction effect was observed. Severity of
      depressive symptoms was also significantly correlated with IL-6, rs = 0.28 and p
      = 0.02, whereas hopelessness was associated with IFN-alpha, rs  = 0.34 and p =
      0.006. Pain, fatigue, and sleep disturbance were associated with several of the
      cytokines assayed including IL-1beta (pain intensity), IL-4 (pain intensity and
      overall sleep quality), IL-12p70 (pain intensity), and TGF-beta (fatigue
      intensity), but anxiety was not associated with any of the cytokines assayed.
      CONCLUSIONS: This study demonstrated an association between depression and IL-6,
      but not with other cytokines. Moreover, IL-6 was not significantly associated
      with other measures of psychological distress (anxiety and hopelessness) or with
      symptom distress (pain, fatigue, and sleep quality), although some cytokines
      assayed were associated with specific symptoms. The implications of these
      findings for the etiology and treatment of depression in pancreatic cancer
      patients are discussed.

PMID- 24136883
TI  - Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple
      negative primary breast cancers; results from the geparquinto study (GBG 44).
AB  - BACKGROUND: We evaluated the pathological complete response (pCR) rate after
      neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing
      chemotherapy with and without the addition of bevacizumab in patients with triple
      negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with untreated cT1c
      4d TNBC represented a stratified subset of the 1948 participants of the HER2
      negative part of the GeparQuinto trial. Patients were randomized to receive four
      cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2);
      q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy.
      RESULTS: TNBC patients were randomized to chemotherapy without (n = 340) or with
      bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9%
      without and 39.3% with bevacizumab (P = 0.003). According to other pCR
      definitions, the addition of bevacizumab increased the pCR rate from 30.9% to
      41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and
      32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95%
      confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95%
      CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P =
      0.009) were confirmed as independent predictors of higher pCR in multivariate
      logistic regression analysis. CONCLUSIONS: The addition of bevacizumab to
      chemotherapy in TNBC significantly increases pCR rates.

PMID- 24136884
TI  - Co-selection may explain high rates of ciprofloxacin non-susceptible Escherichia
      coli from retail poultry reared without prior fluoroquinolone exposure.
AB  - Australia has never permitted fluoroquinolone use in food-producing animals. We
      examined local retail poultry for contamination with fluoroquinolone non
      susceptible Escherichia coli, then explored the hypothesis that their presence
      may be due to co-selection of resistance determinants. Between August and
      November 2010, samples from 30 locally produced, uncooked retail poultry
      carcasses from four different processing centres underwent selective enrichment
      culture for ciprofloxacin non-susceptible E. coli. Their chromosomal- and plasmid
      mediated resistance determinants were characterized, and phylogenetic analysis
      and transformation experiments were performed. Unexpectedly, we found nine (30 %)
      of our small collection of poultry samples carried fluoroquinolone non
      susceptible E. coli of which nearly half possessed aac(6')-Ib-cr, a novel plasmid
      mediated gene encoding an aminoglycoside acetylating enzyme that also confers
      fluoroquinolone resistance. All nine isolates were co-resistant to amoxicillin,
      gentamicin, tetracycline and trimethoprim/sulfamethoxazole--all antibiotic
      classes that are registered for use in poultry reared for food production within
      Australia. Their unique phylogenetic relatedness suggested clonal dissemination
      driven by non-fluoroquinolone selective pressures. aac(6')-Ib-cr was successfully
      transformed and selected for using non-fluoroquinolone antibiotic pressure.
      Vertical and perhaps horizontal co-selection may be contributing to the emergence
      of fluoroquinolone resistance in poultry and could play a similar role in the
      human setting. This suggests that preservation of the usefulness of
      fluoroquinolones may require more than just restriction of their use in isolation
      from other interventions.

PMID- 24136886
TI  - Cell cortex composition and homeostasis resolved by integrating proteomics and
      quantitative imaging.
AB  - The cellular actin cortex is the cytoskeletal structure primarily responsible for
      the control of animal cell shape and as such plays a central role in cell
      division, migration, and tissue morphogenesis. Due to the lack of experimental
      systems where the cortex can be investigated independently from other organelles,
      little is known about its composition, assembly, and homeostasis. Here, we
      describe novel tools to resolve the composition and regulation of the cortex. We
      report and validate a protocol for cortex purification based on the separation of
      cellular blebs. Mass spectrometry analysis of purified cortices provides a first
      extensive list of cortical components. To assess the function of identified
      proteins, we design an automated imaging assay for precise quantification of
      cortical actomyosin assembly dynamics. We show subtle changes in cortex assembly
      dynamics upon depletion of the identified cortical component profilin. Our widely
      applicable integrated method paves the way for systems-level investigations of
      the actomyosin cortex and its regulation during morphogenesis.

PMID- 24136885
TI  - Natural killer cell therapy and aerosol interleukin-2 for the treatment of
      osteosarcoma lung metastasis.
AB  - BACKGROUND: Survival of patients with osteosarcoma lung metastases has not
      improved in 20 years. We evaluated the efficacy of combining natural killer (NK)
      cells with aerosol interleukin-2 (IL-2) to achieve organ-specific NK cell
      migration and expansion in the metastatic organ, and to decrease toxicity
      associated with systemic IL-2. PROCEDURE: Five human osteosarcoma cell lines and
      103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand
      (NKG2DL) expression. Therapeutic efficacy of aerosol IL-2 + NK cells was
      evaluated in vivo compared with aerosol IL-2 alone and NK cells without aerosol
      IL-2. RESULTS: Osteosarcoma cell lines and patient samples expressed various
      levels of NKG2DL. NK-mediated killing was NKG2DL-dependent and correlated with
      expression levels. Aerosol IL-2 increased NK cell numbers in the lung and within
      metastatic nodules but not in other organs. Therapeutic efficacy, as judged by
      tumor number, size, and quantification of apoptosis, was also increased compared
      with NK cells or aerosol IL-2 alone. There were no IL-2-associated systemic
      toxicities. CONCLUSION: Aerosol IL-2 augmented the efficacy of NK cell therapy
      against osteosarcoma lung metastasis, without inducing systemic toxicity. Our
      data suggest that lung-targeted IL-2 delivery circumvents toxicities induced by
      systemic administration. Combining aerosol IL-2 with NK cell infusions, may be a
      potential new therapeutic approach for patients with osteosarcoma lung
      metastasis.

PMID- 24136887
TI  - beta-Naphthoflavone induces oxidative stress in the intertidal copepod, Tigriopus
      japonicus.
AB  - beta-Naphtoflavone (beta-NF) is a flavonoid and enhances oxidative stress in
      vertebrates with little information from aquatic invertebrates as yet. In this
      study, we investigated the effects of beta-NF on the antioxidant defense systems
      of the intertidal copepod Tigriopus japonicus. To measure the beta-NF-triggered
      changes in oxidative stress markers, such as intracellular reactive oxygen
      species (ROS), glutathione (GSH) concentration, residual glutathione S
      transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and
      superoxide dismutase (SOD) activity, T. japonicus were exposed to beta-NF (0.5
      and 1 mg/L) for 72 h. Significant (P < 0.05) induction of the intracellular ROS
      content (%) was observed in 1 mg/L of beta-NF exposed T. japonicus, compared to
      the negative control and H2O2-exposed group. The GSH levels were significantly
      increased in the 0.5 mg/L of beta-NF-exposed group for 12 h and 1 mg/L of beta-NF
      exposed groups for 12-24 h. GPx, GST, and GR activities showed a significant
      increase in the 1 mg/L beta-NF-exposed group, indicating that beta-NF induces
      oxidative stress in T. japonicus. To understand the effects of beta-NF at the
      level of transcript expression, a 6K microarray analysis was employed. Transcript
      profiles of selected antioxidant-related genes were modulated after 72 h exposure
      to 1 mg/L of beta-NF. From microarray data, 10 GST isoforms, GR, GPx, PH-GPx, and
      Se-GPx were chosen for a time-course test by real-time RT-PCR. T. japonicus GST
      S, GST-O, GST-M, and GST-D1 were significantly increased in a 1 mg/L beta-NF
      exposed group. T. japonicus GPx, GR, and Se-GPx mRNA levels were also
      significantly increased at both concentrations. Our results revealed that
      oxidative stress was induced by beta-NF exposure in T. japonicus.

PMID- 24136888
TI  - RASAL1 in thyroid cancer: wisdom from an old foe.

PMID- 24136889
TI  - Identification of RASAL1 as a major tumor suppressor gene in thyroid cancer.
AB  - BACKGROUND: RAS-coupled MAPK and PI3K pathways play a fundamental role in thyroid
      tumorigenesis, and classical genetic alterations upregulating these pathways are
      well characterized. We hypothesized that gene abnormality of negative modulators
      of these signaling pathways might be an important alternative genetic background
      for thyroid cancer. METHODS: By examining gene expression patterns of negative
      modulators of RAS signaling, we attempted to identify potential tumor suppressor
      genes. We then analyzed the methylation and mutation patterns of the identified
      gene in 101 thyroid tumors and tested its functions in vitro and in vivo to
      establish the tumor suppressor role in thyroid cancer. RESULTS: Among 13 negative
      modulators of the RAS pathway screened, RASAL1, encoding a RAS GTPase-activating
      protein, was frequently hypermethylated in thyroid cancers, which was coupled to
      its silencing in thyroid cancer cells. We also, for the first time, identified
      the presence of RASAL1 mutations, with a prevalence of 4.88% (n = 2 of 41) in
      follicular thyroid cancer (FTC) and 16.67% (n = 5 of 30) in anaplastic thyroid
      cancer (ATC). RASAL1 displayed MAPK- and PI3K-suppressing and thyroid tumor
      suppressing activities, which were all impaired by the mutations.
      Hypermethylation and mutations of RASAL1 were mutually exclusive and collectively
      found in zero of 20 benign thyroid tumors, 3.22% (n = 1 of 31) of papillary
      thyroid cancers, 31.70% (n = 13 of 41) of FTCs, and 33.33% (n = 10 of 30) of
      ATCs. A rate of 20.83% (n = 5 of 24) of tumors carrying RASAL1 mutation or
      methylation at high levels (>50%) vs 44.16% (n = 34 of 77) of tumors carrying no
      RASAL1 mutation or methylation at low levels (< 50%) harbored any of the
      classical mutations (two-sided P = .02, Fisher exact test) in RAS, BRAF, PTEN,
      and PIK3CA genes in the MAPK and PI3K pathways, revealing a largely mutually
      exclusive relationship. CONCLUSIONS: We identified RASAL1 as a major tumor
      suppressor gene that is frequently inactivated by hypermethylation and mutations,
      providing a new alternative genetic background for thyroid cancer, particularly
      FTC and ATC.

PMID- 24136890
TI  - Prognostic model predicting metastatic castration-resistant prostate cancer
      survival in men treated with second-line chemotherapy.
AB  - BACKGROUND: Several prognostic models for overall survival (OS) have been
      developed and validated in men with metastatic castration-resistant prostate
      cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and
      validate a prognostic model to predict OS in men who had progressed after first
      line chemotherapy and were selected to receive second-line chemotherapy. METHODS:
      Data from a phase III trial in men with mCRPC who had developed progressive
      disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was
      randomly split into training (n = 507) and testing (n = 248) sets. Another
      dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was
      used for external validation. Adaptive least absolute shrinkage and selection
      operator selected nine prognostic factors of OS. A prognostic score was computed
      from the regression coefficients. The model was assessed on the testing and
      validation sets for its predictive accuracy using the time-dependent area under
      the curve (tAUC). RESULTS: The nine prognostic variables in the final model were
      Eastern Cooperative Oncology Group performance status, time since last docetaxel
      use, measurable disease, presence of visceral disease, pain, duration of hormonal
      use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs
      for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70
      (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively.
      CONCLUSIONS: A prognostic model of OS in the postdocetaxel, second-line
      chemotherapy, mCRPC setting was developed and externally validated. This model
      incorporates novel prognostic factors and can be used to provide predicted
      probabilities for individual patients and to select patients to participate in
      clinical trials on the basis of their prognosis. Prospective validation is
      needed.

PMID- 24136891
TI  - Statistical and practical considerations for clinical evaluation of predictive
      biomarkers.
AB  - Predictive biomarkers to guide therapy for cancer patients are a cornerstone of
      precision medicine. Discussed herein are considerations regarding the design and
      interpretation of such predictive biomarker studies. These considerations are
      important for both planning and interpreting prospective studies and for using
      specimens collected from completed randomized clinical trials. Specific issues
      addressed are differentiation between qualitative and quantitative predictive
      effects, challenges due to sample size requirements for predictive biomarker
      assessment, and consideration of additional factors relevant to clinical utility
      assessment, such as toxicity and cost of new therapies as well as costs and
      potential morbidities associated with routine use of biomarker-based tests.

PMID- 24136892
TI  - Cowden syndrome and the PTEN hamartoma tumor syndrome: how to define rare genetic
      syndromes.

PMID- 24136893
TI  - Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and
      revised diagnostic criteria.
AB  - BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) refers to a spectrum of
      disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene.
      Diagnostic criteria for Cowden syndrome, the principal PTEN-related disorder,
      were first established in 1996 before the identification of the PTEN gene and the
      ability to molecularly confirm a clinical diagnosis. These consortium criteria
      were based on clinical experience and case reports in the existing literature,
      with their inherent selection biases. Although it was initially reported that
      approximately 80% of patients with Cowden syndrome had an identifiable germline
      PTEN mutation, more recent work has shown these diagnostic criteria to be far
      less specific. In addition, increasing evidence has documented the association of
      a broader spectrum of clinical features with PTEN mutations. Our goal was to
      develop revised, evidence-based diagnostic criteria and to include features of
      the broader spectrum of PTEN-related clinical syndromes. METHODS: We performed a
      systematic search and review of the medical literature related to clinical
      features reported in individuals with a PTEN mutation and/or a related clinical
      diagnosis. RESULTS: We found no sufficient evidence to support inclusion of
      benign breast disease, uterine fibroids, or genitourinary malformations as
      diagnostic criteria. There was evidence to include autism spectrum disorders,
      colon cancer, esophageal glycogenic acanthosis, penile macules, renal cell
      carcinoma, testicular lipomatosis, and vascular anomalies. CONCLUSIONS: We
      propose revised, evidence-based criteria covering the spectrum of PTEN-related
      clinical disorders. Additional research on clinical features associated with PTEN
      mutations is warranted.

PMID- 24136894
TI  - Synthesis and properties of a bio-based epoxy resin with high epoxy value and low
      viscosity.
AB  - A bio-based epoxy resin (denoted TEIA) with high epoxy value (1.16) and low
      viscosity (0.92 Pa s, 258C) was synthesized from itaconic acid and its chemical
      structure was confirmed by 1H NMR and 13C NMR spectroscopy. Its curing reaction
      with poly(propylene glycol) bis(2-aminopropyl ether) (D230) and methyl
      hexahydrophthalic anhydride (MHHPA) was investigated. For comparison, the
      commonly used diglycidyl ether of bisphenol A (DGEBA) was also cured with the
      same curing agents. The results demonstrated that TEIA showed higher curing
      reactivity towards D230/MHHPA and lower viscosity compared with DGEBA, resulting
      in the better processability. Owing to its high epoxy value and unique structure,
      comparable or better glass transition temperature as well as mechanical
      properties could be obtained for the TEIA-based network relative to the DGEBA
      based network. The results indicated that itaconic acid is a promising renewable
      feedstock for the synthesis of bio-based epoxy resin with high performance.

PMID- 24136895
TI  - Independent associations between cardiorespiratory fitness, waist circumference,
      BMI, and clustered cardiometabolic risk in adolescents.
AB  - OBJECTIVES: The purpose of this study was to examine the independent associations
      between measures of adiposity and cardiorespiratory fitness (CRF) with clustered
      cardiometabolic risk in adolescents. METHODS: 209 adolescents (139 boys), aged 15
      17.5 years participated. Participants completed anthropometric measurements
      [height, weight, waist circumference (WC)] whilst the 20 m fitness test was used
      to assess CRF. Additional measures included systolic blood pressure,
      triglycerides, ratio total cholesterol/high-density lipoprotein cholesterol,
      insulin resistance (HOMA), interleukin-6, C-reactive protein (CRP), and
      adiponectin. RESULTS: Partial correlations revealed weak to moderate negative
      associations for body mass index (BMI) and WC with CRF (r = -0.295 and -0.292, P
      < 0.001) and adiponectin (r = -0.227 and -0.262, P < 0.05). Weak to moderate
      positive associations were evident for BMI with CRP, and cardiometabolic risk (r
      = 0.274, and 0.283, P < 0.05, respectively). Weak to moderate positive
      associations were apparent for WC with CRP and triglycerides (r = 0.240 and
      0.254, P < 0.05), whilst moderate to large associations were evident for WC with
      clustered cardiometabolic risk (r = 0.317, P < 0.05). Regression analyses
      revealed that BMI was positively associated with cardiometabolic risk (beta =
      0.243, P < 0.001). Further analysis whilst additionally controlling for WC and
      CRF strengthened this association (beta = 0.352, P < 0.001). Finally,
      participants in the least-fit quartile for CRF had significantly poorer
      cardiometabolic risk scores than those in the other quartiles. CONCLUSION: BMI
      and not CRF was independently associated with cardiometabolic risk. Reducing BMI
      appears essential to minimize cardiometabolic risk during adolescence.

PMID- 24136896
TI  - Myoepithelial carcinoma treatment in children: a report from the TREP project.
AB  - BACKGROUND: Myoepithelial carcinoma (MC) of soft tissues is an aggressive tumor
      that rarely affects children, for whom no established treatment protocols exist.
      As part of the TREP (Tumori Rari in Eta Pediatrica) project - an Italian network
      dedicated to children and adolescents with very rare tumors - we present a series
      of patients with MC, who were treated homogeneously and achieved a satisfactory
      outcome. PROCEDURE: From 2005 to 2012, seven patients (age 0.5-9.2 years) with a
      diagnosis of MC were registered in the TREP study. After one patient treated with
      ifosfamide, cisplatin, and etoposide showed tumor shrinkage and experienced long
      term disease remission, all subsequent patients were treated with the same
      chemotherapy regimen. All patients also received radiotherapy. RESULTS: Initial
      surgical management involved a biopsy in three cases and tumor resection in 4.
      Response to initial chemotherapy was evaluable in four patients: two had a
      partial remission, one a minor response and one stable disease. Four patients
      received external-beam radiotherapy and three had brachytherapy. Overall, six
      patients are alive in first complete remission with a median follow-up of 2.5
      years (0.9-5.1 years). CONCLUSIONS: Though our experience is limited to a small
      number of patients, our treatment strategy for patients with MC is appears
      clinically useful and demonstrates how cooperation within the TREP project has
      enabled enough data to be collected to propose treatment recommendations for
      pediatric patients with this very rare tumor.

PMID- 24136897
TI  - Rat lung response to ozone and fine particulate matter (PM2.5) exposures.
AB  - Exposure to different ambient pollutants maybe more toxic to lung than exposure
      to a single pollutant. In this study, we discussed the inflammation and oxidative
      stress responses of rat lung caused by ozone and PM2.5 versus that of rats
      exposed to saline, ozone, or single PM2.5 . Wistar rats inhaled 0.8 ppm ozone or
      air for 4 h and then placed in air for 3 h following intratracheal instillation
      with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM2.5 dissolved
      in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the
      cumulative doses of PM2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were
      sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar
      lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung
      tissues were processed for light microscopic and transmission electron
      microscopic (TEM) examinations. Results showed that total cell number in BALF of
      PM2.5 -exposed groups were higher than control (p < 0.05). PM2.5 instillation
      caused dose-trend increase in tumor necrosis factor alpha (TNF-alpha),
      interleukin-6, lactate dehydrogenase, and total protein of BALF. Exposure to
      ozone alone only caused TNF-alpha significant change in above-mentioned
      indicators of lung injury. On the other hand, ozone could enhance PM2.5-induced
      inflammatory changes and pathological characters in rat lungs. SOD and GSH-Px
      activities in lung were reduced in PM2.5-exposed rats with and without prior
      ozone exposure compared to control. To determine whether the PM2.5 and ozone
      affect endothelium system, iNOS, eNOS, and ICAM-1 mRNA levels in lung were
      analyzed by real-time PCR. These data demonstrated that inflammation and
      oxidative stress were involved in toxicology mechanisms of PM2.5 in rat lung and
      ozone potentiated these effects induced by PM2.5. These results have implications
      for understanding the pulmonary effects induced by ozone and PM2.5.

PMID- 24136898
TI  - OxyR-dependent expression of a novel glutathione S-transferase (Abgst01) gene in
      Acinetobacter baumannii DS002 and its role in biotransformation of
      organophosphate insecticides.
AB  - While screening a genomic library of Acinetobacter baumannii DS002 isolated from
      organophosphate (OP)-polluted soils, nine ORFs were identified coding for
      glutathione S-transferase (GST)-like proteins. These GSTs (AbGST01-AbGST09) are
      phylogenetically related to a number of well-characterized GST classes found in
      taxonomically diverse groups of organisms. Interestingly, expression of Abgst01
      (GenBank accession no. KF151191) was upregulated when the bacterium was grown in
      the presence of an OP insecticide, methyl parathion (MeP). The gene product,
      AbGST01, dealkylated MeP to desMeP. An OxyR-binding motif was identified directly
      upstream of Abgst01. An Abgst-lacZ gene fusion lacking the OxyR-binding site
      showed a drastic reduction in promoter activity. Very low beta-galactosidase
      activity levels were observed when the Abgst-lacZ fusion was mobilized into an
      oxyR (GenBank accession no. KF151190) null mutant of A. baumannii DS002,
      confirming the important role of OxyR. The OxyR-binding sites are not found
      upstream of other Abgst (Abgst02-Abgst09) genes. However, they contained
      consensus sequence motifs that can serve as possible target sites for certain
      well-characterized transcription factors. In support of this observation, the
      Abgst genes responded differentially to different oxidative stress inducers. The
      Abgst genes identified in A. baumannii DS002 are found to be conserved highly
      among all known genome sequences of A. baumannii strains. The versatile
      ecological adaptability of A. baumannii strains is apparent if sequence
      conservation is seen together with their involvement in detoxification processes.

PMID- 24136899
TI  - MRT letter: light sheet based imaging flow cytometry on a microfluidic platform.
AB  - We propose a light sheet based imaging flow cytometry technique for simultaneous
      counting and imaging of cells on a microfluidic platform. Light sheet covers the
      entire microfluidic channel and thus omits the necessity of flow focusing and
      point scanning based technology. Another advantage lies in the orthogonal
      detection geometry that totally cuts-off the incident light, thereby
      substantially reducing the background in the detection. Compared to the existing
      state-of-art techniques the proposed technique shows marked improvement. Using
      fluorescently-coated Saccharomyces cerevisiae cells we have recorded cell
      counting with throughput as high as 2,090 cells/min in the low flow rate regime
      and were able to image the individual cells on-the-go. Overall, the proposed
      system is cost-effective and simple in channel geometry with the advantage of
      efficient counting in operational regime of low laminar flow. This technique may
      advance the emerging field of microfluidic based cytometry for applications in
      nanomedicine and point of care diagnostics.

PMID- 24136900
TI  - Development of a green supercapacitor composed entirely of environmentally
      friendly materials.
AB  - Owing to recent power- and energy-density advances, higher efficiencies, and
      almost unlimited lifetimes, electrical double-layer capacitors (EDLCs, also known
      as supercapacitors) are now used in a wide range of energy harvesting and storage
      systems, which include portable power and grid applications. Despite offering key
      performance advantages, many device components pose significant environmental
      hazards once disposed. They often contain fluorine, sulfur, and cyanide groups,
      which are harmful if discarded by using conventional landfill or incineration
      methods, and they are constructed by using multiple metallic parts, which
      contribute to a high ash content. We explore designs for a fully operational
      supercapacitor that incorporates materials completely safe to dispose of and easy
      to incinerate. The components, which include material alternatives for the
      current collector, electrolyte, separator, particle binder, and packaging, are
      all mutually compatible, and most of them exhibit better performance than
      commonly used materials. We selected a graphite foil as current collector, sodium
      acetate as electrolyte, an ester as porous membrane based on acetate cellulose,
      and polymers based on polyvinyl alcohol as environmentally benign solutions for
      device components. The presented materials all originate from simple and
      inexpensive source compounds, which decreases the environmental impact of their
      manufacture and renders them more viable for integration into commercial devices
      for large-scale stationary and transportation energy storage applications. 

PMID- 24136901
TI  - Life partnerships in childhood cancer survivors, their siblings, and the general
      population.
AB  - BACKGROUND: Life partnerships other than marriage are rarely studied in childhood
      cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in
      CCS and compare them to life partnerships in siblings and the general population;
      and (2) to identify socio-demographic and cancer-related factors associated with
      life partnership and marriage. METHODS: As part of the Swiss Childhood Cancer
      Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20-40 years)
      registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at
      diagnosis, who had survived >= 5 years. The proportion with life partner or
      married was compared between CSS and siblings and participants in the Swiss
      Health Survey (SHS). Multivariable logistic regression was used to identify
      factors associated with life partnership or marriage. RESULTS: We included 1,096
      CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%)
      than siblings (61%, P < 0.001) had life partners, and fewer CCS were married
      (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P <
      0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners.
      CCS who had undergone radiotherapy, bone marrow transplants (global P Treatment =
      0.018) or who had a CNS diagnosis (global P Diagnosis < 0.001) were less likely
      to have life partners. CONCLUSION: CCS are less likely to have life partners than
      their peers. Most CCS with a life partner were not married. Future research
      should focus on the effect of these disparities on the quality of life of CCS.

PMID- 24136903
TI  - Successful management of Churg-Strauss syndrome using omalizumab as adjuvant
      immunomodulatory therapy: first documented pediatric case.
AB  - Churg-Strauss syndrome (CSS) is an anti-neutrophil cytoplasmic antibody (ANCA)
      associated vasculitis; it is extremely rare in childhood and defined according to
      the Chapel-Hill Consensus as an eosinophil-rich and granulomatous inflammation
      involving the respiratory tract and necrotizing vasculitis affecting small to
      medium-sized vessels. Children commonly have a history of asthma and sinusitis
      whilst clinical presentation typically involves pulmonary tract and less
      frequently skin, heart, gastrointestinal tract, and peripheral nerves.
      Cardiopulmonary disease is higher in children and prognosis is worse. It is
      associated with significant eosinophilia and raised serum IgE-levels. ANCA are
      only found in 25% of childhood cases. Here we report the case of a 10-year-old
      girl who presented to us with vomiting, abdominal pain, and weight loss,
      paresthesias of lower extremities and breathlessness as well as a history of
      asthma, sinusitis and allergic rhinitis. She was treated with corticosteroids,
      cyclophosphamide, intravenous immunoglobulin, mycophenolate mofetil (MMF), and
      rituximab. However, remission was only achieved after initiation of omalizumab
      therapy, a recombinant humanized anti-IgE antibody. To the best of our knowledge
      this is the first pediatric patient suffering from CSS successfully managed with
      adjuvant anti-IgE therapy resulting in the control of respiratory as well as
      gastrointestinal symptoms.

PMID- 24136902
TI  - Associations between insulin and heart rate variability in police officers.
AB  - OBJECTIVE: Low heart rate variability (HRV) has been linked to cardiovascular
      disease. Our objective was to examine the cross-sectional association between
      insulin and HRV. METHODS: Insulin levels were measured in 355 nondiabetic
      officers from the BCOPS study, following a 12 h fast. HRV was performed according
      to methods published by the task force of the European Society of Cardiology and
      the North American Society of Pacing Electrophysiology for measurement and
      analysis of HRV. Mean values of high (HF) and low frequency (LF) HRV were
      compared across tertiles of insulin using ANOVA and ANCOVA; p-values were
      obtained from linear regression models. RESULTS: Higher mean levels of insulin
      were significantly associated with lower (i.e., worse) mean levels of HRV before
      and after risk-factor adjustment. The results for HF HRV (ms(2)) were as follows:
      1st insulin (uU/ml) tertile (156.3; 95% confidence interval (CI) = 128.6-189.9);
      2nd tertile (154.3; 95% CI = 124.3-191.5); 3rd tertile (127.9; 95% CI = 105.0
      155.8), p for trend = 0.017. Results with LF HRV were similar to HF HRV. Insulin
      was also inversely and significantly associated with HRV among officers with BMI
      >= 25 kg/m(2), with >= 25.5% body fat, and among those who reported low (<median)
      physical activity scores. CONCLUSIONS: In this cohort, insulin levels were
      inversely and significantly associated with both HF and LF HRV, especially among
      those with higher levels of obesity and lower levels of physical activity,
      suggesting associations with autonomic nervous system function. Prospective
      studies of this association in other populations are warranted.

PMID- 24136904
TI  - Cyclic di-nucleotide signaling enters the eukaryote domain.
AB  - Cyclic (c-di-GMP) is the prevalent intracellular signaling intermediate in
      bacteria. It triggers a spectrum of responses that cause bacteria to shift from a
      swarming motile phase to sessile biofilm formation. However, additional functions
      for c-di-GMP and roles for related molecules, such as c-di-AMP and c-AMP-GMP
      continue to be uncovered. The first usage of cyclic-di-nucleotide (c-di-NMP)
      signaling in the eukaryote domain emerged only recently. In dictyostelid social
      amoebas, c-di-GMP is a secreted signal that induces motile amoebas to
      differentiate into sessile stalk cells. In humans, c-di-NMPs, which are either
      produced endogenously in response to foreign DNA or by invading bacterial
      pathogens, trigger the innate immune system by activating the expression of
      interferon genes. STING, the human c-di-NMP receptor, is conserved throughout
      metazoa and their closest unicellular relatives, suggesting protist origins for
      human c-di-NMP signaling. Compared to the limited number of conserved protein
      domains that detect the second messengers cAMP and cGMP, the domains that detect
      the c-di-NMPs are surprisingly varied.

PMID- 24136905
TI  - Calorie labeling, fast food purchasing and restaurant visits.
AB  - OBJECTIVE: Obesity is a pressing public health problem without proven population
      wide solutions. Researchers sought to determine whether a city-mandated policy
      requiring calorie labeling at fast food restaurants was associated with consumer
      awareness of labels, calories purchased and fast food restaurant visits. DESIGN
      AND METHODS: Difference-in-differences design, with data collected from consumers
      outside fast food restaurants and via a random digit dial telephone survey,
      before (December 2009) and after (June 2010) labeling in Philadelphia (which
      implemented mandatory labeling) and Baltimore (matched comparison city). Measures
      included: self-reported use of calorie information, calories purchased determined
      via fast food receipts, and self-reported weekly fast-food visits. RESULTS: The
      consumer sample was predominantly Black (71%), and high school educated (62%).
      Postlabeling, 38% of Philadelphia consumers noticed the calorie labels for a 33%
      point (P < 0.001) increase relative to Baltimore. Calories purchased and number
      of fast food visits did not change in either city over time. CONCLUSIONS: While
      some consumers report noticing and using calorie information, no population level
      changes were noted in calories purchased or fast food visits. Other controlled
      studies are needed to examine the longer term impact of labeling as it becomes
      national law.

PMID- 24136906
TI  - Inhibition of protein glycation by procyanidin-B2 enriched fraction of cinnamon:
      delay of diabetic cataract in rats.
AB  - Accumulation of advanced glycation endproducts (AGE) from nonenzymatic glycation
      of proteins has been implicated in several diabetic complications including
      diabetic cataract. Previously, we have reported that extracts of dietary agents
      such as cinnamon have the potential to inhibit AGE formation. In this study, we
      have shown procyanidin-B2 as the active component of cinnamon that is involved in
      AGE inhibition using bioassay-guided fractionation of eye lens proteins under in
      vitro conditions. The data indicate that procyanidin-B2 enriched fraction
      scavenges dicarbonyls. Further, procyanidin-B2 fraction of cinnamon inhibited the
      formation of glycosylated hemoglobin in human blood under ex vivo conditions. We
      have also demonstrated the physiological significance of procyanidin-B2 fraction
      in terms of delay of diabetic cataract through inhibition of AGE in diabetic
      rats. These findings establish the antiglycating potential of procyanidin-B2
      fraction of cinnamon which suggests a scope for controlling AGE-mediated diabetic
      complications by food sources that are rich in proanthocyanidins like procyanidin
      B2.

PMID- 24136907
TI  - Human bone-lineage cell responses to anisotropic Ti6Al4V surfaces are dependent
      on their maturation state.
AB  - This article reports on the interactions of human bone cells, mesenchymal stem
      cells (hMSCs) from bone marrow and osteoblasts (hOBs), with a submicron-grooved
      Ti6Al4V alloy that promotes cell orientation in the direction of the anisotropy.
      Adhesion sites, actin and tubulin networks and fibronectin extracellular matrix
      of both cell types align with the direction of the grooves. hMSCs adhere at a
      higher rate on the patterned substrate than on the polished alloy, while no
      differences are found in hOBs attachment. Compared to the flat substrate, RhoA
      activity is higher in hMSCs and hOB cultured on the grooved alloy and treatment
      with C3 transferase leads to loss of organization of actin and tubulin
      cytoskeletons. Rho-associated kinase (ROCK) activity of hMSCs is upregulated on
      the anisotropic samples, but not affected in hOBs. Treatment with hydroxyfasudil
      disrupts the alignment of adhesion sites in hMSCs but not in hOBs. When cells are
      cultured in media that support osteogenic maturation, OPN secretion increases in
      hMSCs on the anisotropic alloy and it remains unaffected in hOBs. Cell layer
      calcification proceeds to a same extent in hMSCs cultured on the two metallic
      surfaces but decreases in hOBs cultured on the patterned samples. Taken together,
      these results indicate that hOBs are less sensitive than hMSCs to the patterned
      Ti6Al4V alloy. This effect can be attributed to their different stages of cell
      maturation and may be mediated, at least in part, through ROCK signaling because
      its activity increases on hMSCs cultured on the patterned alloy, while hOBs fail
      to upregulate it.

PMID- 24136908
TI  - Cutis marmorata telangiectatica congenital.

PMID- 24136909
TI  - Recurrent non-tuberculous mycobacterial keratitis after deep anterior lamellar
      keratoplasty for keratoconus.
AB  - A 26-year-old farmer underwent deep anterior lamellar keratoplasty (DALK) for
      keratoconus. After 3 months, he presented with interface keratitis. Medical
      treatment failed and he underwent a repeat DALK. Microbiological scrapings from
      the interface revealed an infection caused by non-tuberculous mycobacteria.
      Despite the use of intensive antibiotic therapy and a repeat lamellar
      keratoplasty, the infiltrates recurred. The patient underwent therapeutic
      penetrating keratoplasty. Microbiology of the corneal tissue revealed growth of
      Mycobacterium chelonae, and on histopathology, the acid-fast bacilli were noted
      to be located deep at the pre-Descemet level. There was complete resolution of
      the infection with no episodes of recurrence and final best-corrected visual
      acuity was 20/40 at 1 year of follow-up. Medical therapy is unlikely to succeed
      in post-DALK interface keratitis and penetrating rather than lamellar
      keratoplasty may be considered the surgery of choice. 

PMID- 24136910
TI  - Haemolytic anaemia after ingestion of Neem (Azadirachta indica) tea.
AB  - The authors report a clinically relevant and possible cause of haemolytic anaemia
      from ingestion of a Mexican tea from the Neem tree, also known as Azadirachta
      indica, in a 35-year-old Hispanic man who was found to have glucose-6-phosphate
      dehydrogenase deficiency. 

PMID- 24136911
TI  - The first case of mild encephalopathy with a reversible splenial lesion due to
      Japanese encephalitis virus infection.

PMID- 24136912
TI  - Vanishing lung syndrome mistaken for bilateral spontaneous pneumothorax.

PMID- 24136913
TI  - Disseminated histoplasmosis: missed opportunistic infection in a HIV-infected
      patient.
AB  - Oral ulcers are common in HIV-infected patients, with a broad differential,
      including viral, bacterial, fungal, mycobacterial and neoplastic aetiologies. We
      present a case of a patient with AIDS with oral ulcer, which was a cutaneous
      presentation of disseminated histoplasmosis. Our patient responded excellently to
      treatment. 

PMID- 24136914
TI  - Myositis ossificans circumscripta, secondary to high-velocity gunshot and
      fragment wound that causes sciatica.
AB  - This report concerns an unusual cause of sciatica. The case presented is of a
      young man with myositis ossificans that resulted in sciatica and was treated with
      en bloc excision and low-dose radiotherapy and indomethacine. The aim of this
      study was to explain the different diagnostic properties of myositis ossificans
      around the hip and non-classic causes of sciatica. 

PMID- 24136915
TI  - Guillain-Barre syndrome-like illness in association with electrical shock injury.
AB  - A 19-year-old man presented 4 weeks after an electrical shock injury with gradual
      onset limb weakness, altered sensation in the peripheries and respiratory
      difficulty. There was immediate tingling of the fingers following the electrical
      injury that persisted. He subsequently had transient facial weakness responsive
      to oral steroids before the development of further limb symptoms. On admission
      the clinical picture and investigation findings, including neurophysiology,
      cerebrospinal fluid examination and MRI were consistent with a Guillain-Barre
      syndrome. He was managed with a course of intravenous immunoglobulin and
      extensive physiotherapy and occupational therapy. He made an initial modest
      improvement but worsened again over the subsequent 4-6 weeks. Further
      investigation identified no ongoing active disease and he is left with a
      significant residual deficit. 

PMID- 24136916
TI  - Streptophyte algae and the origin of land plants revisited using heterogeneous
      models with three new algal chloroplast genomes.
AB  - The phylogenetic branching order of the green algal groups that gave rise to land
      plants remains uncertain despite its fundamental importance to understanding
      plant evolution. Previous studies have demonstrated that land plants evolved from
      streptophyte algae, but different lineages of streptophytes have been suggested
      to be the sister group of land plants. To better understand the evolutionary
      history of land plants and to determine the potential effects of "long-branch
      attraction" in phylogenetic reconstruction, we analyzed a chloroplast genome data
      set including three new chloroplast genomes from streptophyte algae: Coleochaetae
      orbicularis (Coleochaetales), Nitella hookeri (Charales), and Spirogyra communis
      (Zygnematales). We further applied a site pattern sorting method together with
      site- and time-heterogeneous models to investigate the branching order among
      streptophytes and land plants. Our chloroplast phylogenomic analyses support
      previous hypotheses based on nuclear data in placing Zygnematales alone, or a
      clade consisting of Coleochaetales plus Zygnematales, as the closest living
      relatives of land plants. 

PMID- 24136917
TI  - A novel approach to characterize physical activity patterns in preschool-aged
      children.
AB  - OBJECTIVE: Routine moderate-to-vigorous physical activity (MVPA) is associated
      with better health outcomes; the purpose of this work was to evaluate healthy
      preschooler physical activity patterns with objective measurement. METHODS AND
      PROCEDURES: An objective prospective study of 50 normally developing children 3-5
      years old who were >=50th and <95th BMI percentile and enrolled in a family-based
      healthy lifestyle study in 2011-2012. Participants wore a tri-axial accelerometer
      for 7 continuous days. Outcome measures consisted of wear time examining four
      common MVPA patterns: isolated spurt (IS), isolated sustained activity (ISA),
      clustered spurt (CS), and clustered sustained activity (CSA). RESULTS:
      Participants were 4.3 years, 56% female, 52% African-American, and 26%
      overweight. Forty-five children met wear time criteria. On average, children
      spent 14.5% of wake-wear time in MVPA, requiring 11.3 h to complete 90% of their
      daily MVPA. Children spent the majority of MVPA in CS (62.1%, followed by CSA
      (20.1%). Remaining MVPA was spent in IS (15.5%) and ISA (2.3%). CONCLUSION: It
      takes most of the waking day for preschoolers to attain their PA. They engage in
      short spurts of small duration, in four common MVPA patterns. Utilizing this
      method could better characterize preschooler physical activity needs in practice
      and policy guidelines.

PMID- 24136918
TI  - Renal cells from spermatogonial germline stem cells protect against kidney
      injury.
AB  - Spermatogonial stem cells reside in specific niches within seminiferous tubules
      and continuously generate differentiating daughter cells for production of
      spermatozoa. Although spermatogonial stem cells are unipotent, these cells are
      able to spontaneously convert to germline cell-derived pluripotent stem cells
      (GPSCs) in vitro. GPSCs have many properties of embryonic stem cells and are
      highly plastic, but their therapeutic potential in tissue regeneration has not
      been fully explored. Using a novel renal epithelial differentiation protocol, we
      obtained GPSC-derived tubular-like cells (GTCs) that were functional in vitro, as
      demonstrated through transepithelial electrical resistance analysis. In mice,
      GTCs injected after ischemic renal injury homed to the renal parenchyma, and GTC
      treated mice showed reduced renal oxidative stress, tubular apoptosis, and
      cortical damage and upregulated tubular expression of the antioxidant enzyme
      hemeoxygenase-1. Six weeks after ischemic injury, kidneys of GTC-treated mice had
      less fibrosis and inflammatory infiltrate than kidneys of vehicle-treated mice.
      In conclusion, we show that GPSCs can be differentiated into functionally active
      renal tubular-like cells that therapeutically prevent chronic ischemic damage in
      vivo, introducing the potential utility of GPSCs in regenerative cell therapy. 

PMID- 24136919
TI  - Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through
      downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular
      senescence.
AB  - Sirtuin 1 (SIRT1) depletion in vascular endothelial cells mediates endothelial
      dysfunction and premature senescence in diverse cardiovascular and renal
      diseases. However, the molecular mechanisms underlying these pathologic effects
      remain unclear. Here, we examined the phenotype of a mouse model of vascular
      senescence created by genetically ablating exon 4 of Sirt1 in endothelial cells
      (Sirt1(endo-/-)). Under basal conditions, Sirt1(endo-/-) mice showed impaired
      endothelium-dependent vasorelaxation and angiogenesis, and fibrosis occurred
      spontaneously at low levels at an early age. In contrast, induction of
      nephrotoxic stress (acute and chronic folic acid-induced nephropathy) in
      Sirt1(endo-/-) mice resulted in robust acute renal functional deterioration
      followed by an exaggerated fibrotic response compared with control animals.
      Additional studies identified matrix metalloproteinase-14 (MMP-14) as a target of
      SIRT1. In the kidneys of Sirt1(endo-/-) mice, impaired angiogenesis, reduced
      matrilytic activity, and retention of the profibrotic cleavage substrates tissue
      transglutaminase and endoglin accompanied MMP-14 suppression. Furthermore,
      restoration of MMP-14 expression in SIRT1-depeleted mice improved angiogenic and
      matrilytic functions of the endothelium, prevented renal dysfunction, and
      attenuated nephrosclerosis. Our findings establish a novel mechanistic molecular
      link between endothelial SIRT1 depletion, downregulation of MMP-14, and the
      development of nephrosclerosis. 

PMID- 24136920
TI  - Evidence-based cardiology in hemodialysis patients.
AB  - Cardiac events are the major cause of death in hemodialysis patients. Because of
      the paucity of randomized clinical trials (RCTs) in hemodialysis patients, most
      cardiovascular therapies in this population are based on observational studies or
      results extrapolated from studies that excluded hemodialysis patients. However,
      associations discovered in observational studies do not prove causality, and
      these studies often report surrogate outcomes rather than clinical end points.
      Furthermore, interventions that show effectiveness in the general population may
      have drastically different outcomes and side effect profiles in hemodialysis
      patients. This review discusses the results of RCTs undertaken recently to
      evaluate cardiovascular therapies in hemodialysis patients and emphasizes
      clinically relevant outcomes. Although some interventions have produced similar
      outcomes in hemodialysis patients and the general population, others have not,
      suggesting that the management of cardiovascular disease in hemodialysis patients
      may require strategies that differ from the best practice guidelines applied to
      general population. 

PMID- 24136921
TI  - Met activation is required for early cytoprotection after ischemic kidney injury.
AB  - Renal proximal tubule epithelial cells express high levels of the hepatocyte
      growth factor receptor Met, and both the receptor and ligand are upregulated
      after ischemic injury. Activation of the Met receptor after hepatocyte growth
      factor stimulation in vitro promotes activities involved in kidney repair,
      including cell survival, migration, and proliferation. However, characterizing
      the in vivo role of these signaling events in proximal tubule responses to kidney
      injury has been difficult because global Met knockout results in embryonic
      lethality due to placental and liver abnormalities. Here, we used gammaGT-Cre to
      knockout Met receptor expression selectively in the proximal tubules of mice
      (gammaGT-Cre;Met(fl/fl)). The kidneys of these mice developed normally, but
      exhibited increased initial tubular injury, tubular cell apoptosis, and serum
      creatinine after ischemia/reperfusion compared with gammaGT-Cre;Met(+/+) kidneys.
      These changes in gammaGT-Cre;Met(fl/fl) mice correlated with a selective
      reduction in PI3K/Akt activation in response to injury and subsequent decreases
      in inhibitory phosphorylation of the proapoptotic factor Bad and activating
      phosphorylation of the ribosomal regulatory protein p70-S6 kinase. Moreover,
      tubular cell proliferation after ischemia/reperfusion was delayed in gammaGT
      Cre;Met(fl/fl) mice. In conclusion, this study identifies Met-dependent
      phosphoinositide 3-kinase activation in proximal tubules as a critical
      determinant of initial tubular cell survival and reparative proliferation after
      ischemic injury. 

PMID- 24136922
TI  - Regulatory T cells in AKI.
AB  - Human AKI is manifested by inflammation, and an early feature in the pathogenesis
      is the accumulation of immune cells in the kidney. To understand the
      pathophysiology of AKI, results from animal models have shown a causal relation
      between the leukocyte activation and infiltration to the kidney after kidney
      ischemia-reperfusion. Blocking the activation or trafficking of proinflammatory
      leukocytes into the kidney preserves renal function and histologic integrity. In
      contrast, the anti-inflammatory lymphocytes called regulatory T cells have an
      intrinsic renal-protective function and may represent a novel therapeutic
      approach and/or target for pharmacological manipulation to ameliorate AKI. This
      review will highlight the recent insight gained into the role and mechanisms of
      regulatory T cells in AKI. 

PMID- 24136923
TI  - Nuclear translocation of nuclear factor of activated T cells (NFAT) as a
      quantitative pharmacodynamic parameter for tacrolimus.
AB  - Nuclear factor of activated T cells (NFAT) is a family of transcription factors
      involved in regulating the immune response. The canonical NFAT pathway is calcium
      dependent and upon activation, NFAT is dephosphorylated by the phosphatase,
      calcineurin. This results in its translocation from the cytoplasm to the nucleus
      and transcription of downstream target genes that include the cytokines IL-2, IL
      10, and IFNgamma. Calcineurin inhibitors including tacrolimus inhibit the NFAT
      pathway and are used as immunosuppressants in transplant settings to prevent
      graft rejection. There is, as yet, no direct means to monitor tacrolimus
      pharmacodynamics. In this study, a rapid, quantitative, image cytometry-based
      measurement of nuclear translocation of NFAT1 is used to evaluate NFAT activation
      in T cells and its tacrolimus-induced inhibition. A strong dose-dependent
      correlation between NFAT1 inhibition and tacrolimus dose is demonstrated in
      vitro. Time kinetic analysis of NFAT1 inhibition in plasma from stable renal
      transplant recipients before and after an in vivo dose with tacrolimus correlated
      with the expected pharmacokinetic profile of tacrolimus. This was further
      corroborated by analysis of patients' autologous CD4 and CD8 T cells. This is the
      first report to show that the measurement of NFAT1 activation potential by
      nuclear translocation can be used as a direct, sensitive, reproducible and
      quantitative pharmacodynamic readout for tacrolimus action. These results, and
      the rapid turnaround time for this assay, warrant its evaluation in a larger
      clinical setting to assess its role in therapeutic drug monitoring of calcineurin
      inhibitors.

PMID- 24136924
TI  - Longitudinal trajectories of BMI and cardiovascular disease risk: the national
      longitudinal study of adolescent health.
AB  - OBJECTIVE: In adulthood, excess BMI is associated with cardiovascular disease
      (CVD); it is unknown whether risk differs by BMI trajectories from adolescence to
      adulthood. DESIGN AND METHODS: The National Longitudinal Study of Adolescent
      Health, a nationally representative, longitudinal adolescent cohort (mean age:
      16.9 years) followed into adulthood (mean age: 28.8 years) [n = 13,984
      individuals (41,982 observations)] was examined. Separate logistic regression
      models for diabetes, hypertension, and inflammation were used to examine odds of
      risk factors at given adult BMI according to varying BMI trajectories from
      adolescence to adulthood. RESULTS: CVD risk factor prevalence at follow-up ranged
      from 5.5% (diabetes) to 26.4% (hypertension) and 31.3% (inflammation); risk
      differed across BMI trajectories. For example, relative to men aged 27 years (BMI
      = 23 kg/m(2) maintained over full study period), odds for diabetes were
      comparatively higher for men of the same age and BMI ~ 30 kg/m(2) with ~8 BMI
      unit gain between 15 and 20 years (OR = 2.35; 95% CI, 1.51, 3.66) or in those who
      maintained BMI ~ 30 kg/m(2) across the study period (OR = 2.33; 1.92, 2.83)
      relative to the same ~8 BMI unit gain, but between 20 and 27 years (OR = 1.44;
      1.10, 1.87). CONCLUSIONS: Specific periods and patterns of weight gain in the
      transition from adolescence to adulthood might be critical for CVD preventive
      efforts.

PMID- 24136925
TI  - Prevalence of obstructive coronary artery disease in patients undergoing lung
      transplantation: case series and review of the literature.
AB  - BACKGROUND: Coronary angiography is commonly performed prior to lung
      transplantation, but its utility is unproven. METHODS: We conducted a single
      center retrospective analysis of consecutive patients referred for coronary
      angiography as part of a pre-operative evaluation for lung transplantation and
      reviewed the literature for prior series. RESULTS: A total of 89 patients, 48 men
      and 41 women were included. Obstructive (>=70% stenosis) CAD was present in 9
      (10%), non-obstructive (<70% stenosis) CAD in 24 (27%), and no angiographic
      evidence of CAD in 56 (63%) patients. We found 13 previously published series in
      the literature, in which a total of 1998 patients underwent coronary angiography
      pre-lung transplant. Together with our 89 patients, obstructive CAD was found in
      11%. CONCLUSIONS: In conclusion, given the low prevalence of obstructive CAD in
      patients referred for lung transplantation, the inherent risk of angiography, and
      unproven benefit of detection of obstructive CAD, the utility of routine coronary
      angiography in this population requires validation in prospective studies.

PMID- 24136926
TI  - Executive control circuitry differentiates degree of success in weight loss
      following gastric-bypass surgery.
AB  - OBJECTIVE: While overall success rates of bariatric surgery are high,
      approximately 20% of patients either regain or never lose the expected amount of
      weight. The purpose of this study was to determine whether, after gastric-bypass
      surgery, the degree of weight loss can be differentiated based on the neural
      response to food cues. DESIGN AND METHODS: In this functional MRI study, 31 post
      surgical patients viewed food and neutral images in two counterbalanced runs
      during which they were either instructed to "crave" or to "resist" craving. The
      neural response to food cues was assessed within and between runs for all
      participants, and further analyzed between more successful (n = 24) and less
      successful (n = 7) groups. More successful was defined by meeting 50% excess
      weight loss. RESULTS: Overall, instructions to "crave" elicited significant
      activity in the dorsomedial prefrontal cortex (PFC) whereas "resist" elicited
      significant activity in the dorsolateral PFC (DLPFC). Between groups there was no
      brain difference when instructed to "crave." The more successful participants
      however had significantly more activity in the DLPFC when instructed to "resist."
      CONCLUSIONS: These findings suggest that the ability to mobilize neural circuits
      involved in executive control post-gastric-bypass surgery may be a unique
      component of successful outcome post-surgery.

PMID- 24136927
TI  - A rapid and sensitive method based on magnetic beads for the detection of
      hepatitis B virus surface antigen in human serum.
AB  - Current clinically assays, such as enzyme-linked immunosorbent assay and
      chemiluminescence immunoassay, for hepatitis B surface antigen (HBsAg) are
      inferior in terms of either sensitivity and accuracy or rapid and high-throughput
      analysis. A novel assay based on magnetic beads and time-resolved
      fluoroimmunoassay was developed for the quantitative determination of HBsAg in
      human serum. HBsAg was captured using two types of anti-HBsAg monoclonal
      antibodies (B028, S015) immobilized on to magnetic beads and detected using
      europium-labeled anti-HBsAg polyclonal detection antibody. Finally, the assay
      yielded a high sensitivity (0.02 IU/mL) and a wide dynamic range (0.02-700 IU/mL)
      for HBsAg when performed under optimal conditions. Satisfactory accuracy,
      recovery and specificity were also demonstrated. The intra- and interassay
      coefficients of variation were 4.7-8.7% and 3.8-7.5%, respectively. The
      performance of this assay was further assessed against a well-established
      commercial chemiluminescence immunoassay kit with 399 clinical serum samples. It
      was revealed that the test results for the two methods were in good correlation
      (Y = 1.182X - 0.017, R = 0.989). In the current study, we demonstrated that this
      novel time-resolved fluoroimmunoassay could be used: as a highly sensitive,
      automated and high-throughput immunoassay for the diagnosis of acute or chronic
      hepatitis B virus infection; for the screening of blood or organ donors; and for
      the surveillance of persons at risk of acquiring or transmitting hepatitis B
      virus.

PMID- 24136928
TI  - Evaluation of phentermine and topiramate versus phentermine/topiramate extended
      release in obese adults.
AB  - OBJECTIVE: A 28-week, randomized, controlled trial compared the combination of
      phentermine and topiramate extended-release (PHEN/TPM ER) with its components as
      monotherapies and with placebo in obese adults. DESIGN AND METHODS: Subjects were
      randomized to placebo, phentermine 7.5 mg, phentermine 15 mg, topiramate ER 46
      mg, topiramate ER 92 mg, PHEN/TPM ER 7.5/46 mg, or PHEN/TPM ER 15/92 mg. All
      subjects received lifestyle intervention counseling. Primary endpoints were
      percent weight loss (WL) and achievement of >=5% WL. RESULTS: At week 28,
      PHEN/TPM ER 7.5/46 (-8.5%) and 15/92 (-9.2%) achieved greater percentage WL
      versus placebo (-1.7%; P < 0.0001) and their respective monotherapies (P < 0.05).
      The percentage of subjects achieving >=5% WL was 15.5% for placebo, 43.3% for
      phentermine 7.5, 46.2% for phentermine 15, 39.2% for topiramate ER 46, 48.6% for
      topiramate ER 92, 62.1% for PHEN/TPM ER 7.5/46, and 66.0% for PHEN/TPM ER 15/92.
      PHEN/TPM ER was generally well tolerated; comprehensive assessment of cognitive
      functions with the Repeatable Battery for Assessment of Neuropsychological Status
      revealed impairment only in the attention domain. CONCLUSIONS: PHEN/TPM ER
      demonstrated greater WL when used in combination than when used as monotherapies,
      suggesting enhanced ability of the combination formulation to induce WL at doses
      lower than with available monotherapies.

PMID- 24136930
TI  - The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2
      negative hereditary breast cancer.
AB  - BACKGROUND: Several reports indicate that inherited mutations in the PALB2 gene
      predispose to breast cancer. However, there is little agreement about the
      clinical relevance and usefulness of mutation screening in this gene. We analyzed
      the prevalence and spectrum of germline mutations in PALB2 to estimate their
      contribution to hereditary breast and/or ovarian cancer in the Czech Republic.
      METHODS: The entire PALB2 coding region was sequenced in 409 breast/ovarian
      cancer patients negative for BRCA1 and BRCA2 mutations. Testing for large genomic
      rearrangements (LGR) was performed by multiplex ligation-dependent probe
      amplification (MLPA) analysis. RESULTS: We have identified 13 different
      pathogenic alterations including 10 truncating mutations and three LGRs in 16 of
      409 patients (3.9%), whereas one truncating mutation was found in a group of
      1,226 controls (0.08%; P = 2.6 * 10(-9)). Three novel LGRs included deletions
      involving exons 7-8 and 9-10, respectively, and a duplication spanning exons 9
      11. Five frameshift and two nonsense mutations were novel, whereas three
      truncating mutations were described previously. The only recurrent mutation was
      the c.172_175delTTGT detected in four unrelated breast cancer individuals.
      CONCLUSIONS: Our analyses demonstrated the significant role of the PALB2 gene in
      breast cancer susceptibility. The highest frequency of PALB2 mutations
      (comparable with that previously reported for BRCA2) was found in a subgroup of
      patients with hereditary breast cancer (HBC) (13/235; 5.5%). IMPACT: Our results
      show that mutation analysis of the PALB2 gene, including the analysis of LGRs, is
      primarily indicated in patients with HBC in case of their BRCA1 and BRCA2
      negativity.

PMID- 24136929
TI  - Genes-environment interactions in obesity- and diabetes-associated pancreatic
      cancer: a GWAS data analysis.
AB  - BACKGROUND: Obesity and diabetes are potentially alterable risk factors for
      pancreatic cancer. Genetic factors that modify the associations of obesity and
      diabetes with pancreatic cancer have previously not been examined at the genome
      wide level. METHODS: Using genome-wide association studies (GWAS) genotype and
      risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted
      a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and
      gene-diabetes interactions in relation to pancreatic cancer risk by using the
      likelihood-ratio test nested in logistic regression models and Ingenuity Pathway
      Analysis (IPA). RESULTS: After adjusting for multiple comparisons, a significant
      interaction of the chemokine signaling pathway with obesity (P = 3.29 * 10(-6))
      and a near significant interaction of calcium signaling pathway with diabetes (P
      = 1.57 * 10(-4)) in modifying the risk of pancreatic cancer were observed. These
      findings were supported by results from IPA analysis of the top genes with
      nominal interactions. The major contributing genes to the two top pathways
      include GNGT2, RELA, TIAM1, and GNAS. None of the individual genes or single
      nucleotide polymorphism (SNP) except one SNP remained significant after adjusting
      for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an
      interaction with diabetes (P = 7.91 * 10(-7)) at a false discovery rate of 6%.
      CONCLUSIONS: Genetic variations in inflammatory response and insulin resistance
      may affect the risk of obesity- and diabetes-related pancreatic cancer. These
      observations should be replicated in additional large datasets. IMPACT: A gene
      environment interaction analysis may provide new insights into the genetic
      susceptibility and molecular mechanisms of obesity- and diabetes-related
      pancreatic cancer.

PMID- 24136931
TI  - In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for
      treatment of liver malignancies.
AB  - (166)Ho-poly(l-lactic acid) microspheres allow for quantitative imaging with MR
      imaging or SPECT for microsphere biodistribution assessment after
      radioembolization. The purpose of this study was to evaluate SPECT- and MR
      imaging-based dosimetry in the first patients treated with (166)Ho
      radioembolization. METHODS: Fifteen patients with unresectable, chemorefractory
      liver metastases of any origin were enrolled in this phase 1 study and were
      treated with (166)Ho radioembolization according to a dose escalation protocol
      (20-80 Gy). The contours of all liver segments and all discernible tumors were
      manually delineated on T2-weighted posttreatment MR images and registered to the
      posttreatment SPECT images (n = 9) or SPECT/CT images (n = 6) and MR imaging
      based R2* maps (n = 14). Dosimetry was based on SPECT (n = 15) and MR imaging (n
      = 9) for all volumes of interest, tumor-to-nontumor (T/N) activity concentration
      ratios were calculated, and correlation and agreement of MR imaging- and SPECT
      based measurements were evaluated. RESULTS: The median overall T/N ratio was 1.4
      based on SPECT (range, 0.9-2.8) and 1.4 based on MR imaging (range, 1.1-3.1). In
      6 of 15 patients (40%), all tumors had received an activity concentration equal
      to or higher than the normal liver (T/N ratio >= 1). Analysis of SPECT and MR
      imaging measurements for dose to liver segments yielded a high correlation (R(2)
      = 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, 
      11.2 to 18.7). CONCLUSION: With the use of (166)Ho-microspheres, in vivo
      dosimetry is feasible on the basis of both SPECT and MR imaging, which enables
      personalized treatment by selective targeting of inadequately treated tumors.

PMID- 24136932
TI  - Imaging of epidermal growth factor receptor expression in head and neck cancer
      with SPECT/CT and 111In-labeled cetuximab-F(ab')2.
AB  - Combined treatment of advanced head and neck squamous cell carcinomas (HNSCC)
      with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor
      cetuximab improves clinical outcome in comparison to radiotherapy alone but is
      effective only in a few cases. To select those patients most likely to benefit
      from EGFR inhibition, it can be advantageous to quantify the tumor EGFR status
      before and possibly during therapy. The aim of this study was to develop and
      characterize the (111)In-cetuximab-F(ab')2 tracer to image EGFR targeting in
      vivo. METHODS: The affinity and internalization kinetics of (111)In-cetuximab
      F(ab')2 were determined in vitro. The optimal protein-fragment dose for imaging
      was determined in nude mice with a subcutaneous head and neck carcinoma model
      (FaDu). Mice with FaDu tumors were imaged using ultra-high-resolution SPECT with
      (111)In-cetuximab-F(ab')2 or (111)In-cetuximab IgG at 4, 24, 48, and 168 h after
      injection. Tumor tracer uptake was determined on micro-SPECT and autoradiography
      images of tumor sections. Immunohistochemical staining was used to analyze EGFR
      expression in the tumor. RESULTS: In vitro, more than 50% of (111)In-cetuximab
      F(ab')2 was internalized into FaDu cells within 24 h. The half maximal inhibitory
      concentration (IC50) of (111)In-cetuximab-F(ab')2 and (111)In-cetuximab was
      similar: 0.42 +/- 0.16 nM versus 0.28 +/- 0.14 nM, respectively. The protein dose
      escalation study showed that the highest uptake of (111)In-cetuximab-F(ab')2 in
      tumors was obtained at doses of 10 MUg/mouse or less (13.5 +/- 5.2 percentage
      injected dose per gram [%ID/g]). Tumor uptake of (111)In-cetuximab was
      significantly higher (26.9 +/- 3.3 %ID/g, P < 0.01). However, because of rapid
      blood clearance, tumor-to-blood ratios at 24 h after injection were significantly
      higher for (111)In-cetuximab-F(ab')2 (31.4 +/- 3.8 vs. 1.7 +/- 0.2, respectively;
      P < 0.001). The intratumoral distribution of (111)In-cetuximab-F(ab')2 correlated
      well with the immunohistochemical distribution of EGFR (r = 0.64 +/- 0.06, P <
      0.0001). micro-SPECT images of (111)In-cetuximab-F(ab')2 clearly showed
      preferential uptake in the tumor from 4 h onward, with superior tumor-to
      background contrast at 24 h, compared with (111)In-cetuximab (107.0 +/- 17.0 vs.
      69.7 +/- 3.9, respectively; P < 0.05). CONCLUSION: (111)In-cetuximab-F(ab')2
      displays higher tumor-to-blood ratios early after injection than (111)In
      cetuximab in an HNSCC model, making it more suitable for EGFR visualization and
      potentially for selecting patients for treatment with EGFR inhibitors.

PMID- 24136933
TI  - Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in
      the MENX tumor model.
AB  - We evaluated (18)F-LMI1195 (1-(3-bromo-4-(3-(18)F-fluoro
      propoxy)benzyl)guanidine), a metaiodobenzylguanidine (MIBG) analog, for the
      detection of pheochromocytoma in a preclinical in vivo model of endogenous
      neuroendocrine tumors (multiple endocrine neoplasia [MENX]). METHODS: Adrenal
      uptake kinetics of (18)F-LMI1195 were evaluated in healthy Wistar rats (n = 6) by
      dynamic PET imaging. Distribution of (18)F-LMI1195 was evaluated in tumor-bearing
      MENX mut/mut rats (n = 10) and control MENX wild-type rats (n = 4) by
      biodistribution studies and PET imaging. Biodistribution of (18)F-LMI1195 was
      compared with (123)I-MIBG in MENX mut/mut rats (n = 6) and correlated with
      histological tumor volume and norepinephrine transporter (NET) expression. Uptake
      specificity was evaluated by in vivo inhibition of the NET by desipramine (n =
      6). Intraadrenal distribution of (18)F-LMI1195 was evaluated by autoradiography.
      RESULTS: (18)F-LMI1195 showed rapid tracer accumulation in adrenal glands 1 min
      after tracer injection. Adrenal glands of MENX mut/mut animals showed
      significantly higher standardized uptake value than MENX wild-type controls
      (maximum SUV, 10.3 +/- 2.3 vs. 6.1 +/- 0.9, P < 0.01). Adrenal uptake in MENX
      mut/mut rats could be inhibited by desipramine, shown by biodistribution studies
      (0.06 +/- 0.01 vs. 0.16 +/- 0.05 percentage injected dose, P < 0.01), PET imaging
      (maximum SUV, 3.8 +/- 0.8 vs. 10.3 +/- 2.3, P < 0.01), and autoradiography.
      Adrenal uptake of (18)F-LMI1195 correlated with (123)I-MIBG uptake (r = 0.91),
      histological tumor volume (r = 0.68), and NET expression (r = 0.50). (18)F
      LMI1195 showed an overall favorable distribution for tumor imaging. CONCLUSION:
      (18)F-LMI1195 shows high and specific accumulation in pheochromocytomas. Its
      favorable biodistribution makes it a promising PET tracer for tumor imaging.
      Further studies are warranted to evaluate its clinical value in oncologic
      indications.

PMID- 24136934
TI  - Biodistribution and radiation dosimetry of 18F-CP-18, a potential apoptosis
      imaging agent, as determined from PET/CT scans in healthy volunteers.
AB  - (18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30
      ((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1
      yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24
      isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28
      pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis
      marker for PET imaging. The purpose of this study was to determine the
      biodistribution and estimate the normal-organ radiation-absorbed doses and
      effective dose from (18)F-CP-18. METHODS: Successive whole-body PET/CT scans were
      obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection
      of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were
      collected between the PET/CT scans, and the biostability of (18)F-CP-18 was
      assessed using high-performance liquid chromatography. The PET scans were
      analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM
      software was used to calculate human radiation doses based on the biodistribution
      of the tracer. RESULTS: (18)F-CP-18 was 54% intact in human blood at 135 min
      after injection. The tracer cleared rapidly from the blood pool with a half-life
      of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the
      kidneys and bladder, with diffuse uptake in the liver and heart. The mean
      standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at
      around 50 min after injection were approximately 65, 6, 1.5, and 1.5,
      respectively. The calculated effective dose was 38 +/- 4 MUSv/MBq, with the
      urinary bladder wall having the highest absorbed dose at 536 +/- 61 MUGy/MBq
      using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding
      interval, these doses were reduced to 15 +/- 2 MUSv/MBq and 142 +/- 15 MUGy/MBq,
      respectively. For a typical injected activity of 555 MBq, the effective dose
      would be 21.1 +/- 2.2 mSv for the 4.8-h interval, reduced to 8.3 +/- 1.1 mSv for
      the 1-h interval. CONCLUSION: (18)F-CP-18 cleared rapidly through the renal
      system. The urinary bladder wall received the highest radiation dose and was
      deemed the critical organ. Both the effective dose and the bladder dose can be
      reduced by frequent voiding. From the radiation dosimetry perspective, the
      apoptosis imaging agent (18)F-CP-18 is suitable for human use.

PMID- 24136935
TI  - Early PET/CT scan is more effective than RECIST in predicting outcome of patients
      with liver metastases from colorectal cancer treated with preoperative
      chemotherapy plus bevacizumab.
AB  - Markers predictive of treatment effect might be useful to improve the treatment
      of patients with metastatic solid tumors. Particularly, early changes in tumor
      metabolism measured by PET/CT with (18)F-FDG could predict the efficacy of
      treatment better than standard dimensional Response Evaluation Criteria In Solid
      Tumors (RECIST) response. METHODS: We performed PET/CT evaluation before and
      after 1 cycle of treatment in patients with resectable liver metastases from
      colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus
      bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the
      total lesion glycolysis (TLG) were determined. On the basis of previous studies,
      a <= -50% change from baseline was used as a threshold for significant metabolic
      response for maximum SUV and, exploratively, for TLG. Standard RECIST response
      was assessed with CT after 3 mo of treatment. Pathologic response was assessed in
      patients undergoing resection. The association between metabolic and CT/RECIST
      and pathologic response was tested with the McNemar test; the ability to predict
      progression-free survival (PFS) and overall survival (OS) was tested with the Log
      rank test and a multivariable Cox model. RESULTS: Thirty-three patients were
      analyzed. After treatment, there was a notable decrease of all the parameters
      measured by PET/CT. Early metabolic PET/CT response (either SUV- or TLG-based)
      had a stronger, independent and statistically significant predictive value for
      PFS and OS than both CT/RECIST and pathologic response at multivariate analysis,
      although with different degrees of statistical significance. The predictive value
      of CT/RECIST response was not significant at multivariate analysis. CONCLUSION:
      PET/CT response was significantly predictive of long-term outcomes during
      preoperative treatment of patients with liver metastases from colorectal cancer,
      and its predictive ability was higher than that of CT/RECIST response after 3 mo
      of treatment. Such findings need to be confirmed by larger prospective trials.

PMID- 24136936
TI  - Science demystified.

PMID- 24136941
TI  - Paleoanthropology. Stunning skull gives a fresh portrait of early humans.

PMID- 24136942
TI  - Prizes. Molecule and market studies capture Nobel laurels.

PMID- 24136943
TI  - Policy. U.S. shutdown disrupts long-term ecosystem studies.

PMID- 24136944
TI  - Neuroscience. Sleep: the brain's housekeeper?

PMID- 24136945
TI  - Asia. South Korea's charge into basic research meets resistance.

PMID- 24136946
TI  - Food security. Botanists spread the gospel that breadfruit can be manna.

PMID- 24136947
TI  - Roving into martian waters.

PMID- 24136948
TI  - Climate change. Dr. Cool.

PMID- 24136949
TI  - China's rapid urbanization.

PMID- 24136950
TI  - Gain-of-function research: unproven technique.

PMID- 24136951
TI  - Gain-of-function research: unknown risks.

PMID- 24136953
TI  - Science and regulation. Probiotics: finding the right regulatory balance.

PMID- 24136954
TI  - Neuroscience. Sleep it out.

PMID- 24136955
TI  - Applied physics. Perovskite-based solar cells.

PMID- 24136957
TI  - Materials science. How to be both strong and thermally stable.

PMID- 24136956
TI  - Neuroscience. Path to treat Rett syndrome.

PMID- 24136958
TI  - Paleontology. Did the Denisovans cross Wallace's Line?

PMID- 24136959
TI  - Materials science. Soft acoustic metamaterials.

PMID- 24136960
TI  - A complete skull from Dmanisi, Georgia, and the evolutionary biology of early
      Homo.
AB  - The site of Dmanisi, Georgia, has yielded an impressive sample of hominid cranial
      and postcranial remains, documenting the presence of Homo outside Africa around
      1.8 million years ago. Here we report on a new cranium from Dmanisi (D4500) that,
      together with its mandible (D2600), represents the world's first completely
      preserved adult hominid skull from the early Pleistocene. D4500/D2600 combines a
      small braincase (546 cubic centimeters) with a large prognathic face and exhibits
      close morphological affinities with the earliest known Homo fossils from Africa.
      The Dmanisi sample, which now comprises five crania, provides direct evidence for
      wide morphological variation within and among early Homo paleodemes. This implies
      the existence of a single evolving lineage of early Homo, with phylogeographic
      continuity across continents. 

PMID- 24136961
TI  - Stellar spin-orbit misalignment in a multiplanet system.
AB  - Stars hosting hot Jupiters are often observed to have high obliquities, whereas
      stars with multiple coplanar planets have been seen to have low obliquities. This
      has been interpreted as evidence that hot-Jupiter formation is linked to
      dynamical disruption, as opposed to planet migration through a protoplanetary
      disk. We used asteroseismology to measure a large obliquity for Kepler-56, a red
      giant star hosting two transiting coplanar planets. These observations show that
      spin-orbit misalignments are not confined to hot-Jupiter systems. Misalignments
      in a broader class of systems had been predicted as a consequence of torques from
      wide-orbiting companions, and indeed radial velocity measurements revealed a
      third companion in a wide orbit in the Kepler-56 system. 

PMID- 24136962
TI  - Gravitational-wave limits from pulsar timing constrain supermassive black hole
      evolution.
AB  - The formation and growth processes of supermassive black holes (SMBHs) are not
      well constrained. SMBH population models, however, provide specific predictions
      for the properties of the gravitational-wave background (GWB) from binary SMBHs
      in merging galaxies throughout the universe. Using observations from the Parkes
      Pulsar Timing Array, we constrain the fractional GWB energy density (Omega(GW))
      with 95% confidence to be Omega(GW)(H0/73 kilometers per second per
      megaparsec)(2) < 1.3 * 10(-9) (where H0 is the Hubble constant) at a frequency of
      2.8 nanohertz, which is approximately a factor of 6 more stringent than previous
      limits. We compare our limit to models of the SMBH population and find
      inconsistencies at confidence levels between 46 and 91%. For example, the
      standard galaxy formation model implemented in the Millennium Simulation Project
      is inconsistent with our limit with 50% probability.

PMID- 24136963
TI  - Strain-induced ultrahard and ultrastable nanolaminated structure in nickel.
AB  - Heavy plastic deformation may refine grains of metals and make them very strong.
      But the strain-induced refinement saturates at large strains, forming three
      dimensional ultrafine-grained (3D UFG) structures with random orientations.
      Further refinement of this microstructure is limited because of the enhanced
      mobility of grain boundaries. Very-high-rate shear deformation with high strain
      gradients was applied in the top surface layer of bulk nickel, where a 2D
      nanometer-scale laminated structure was induced. The strongly textured
      nanolaminated structure (average lamellar thickness of 20 nanometers) with low
      angle boundaries among the lamellae is ultrahard and ultrastable: It exhibits a
      hardness of 6.4 gigapascal--which is higher than any reported hardness of the UFG
      nickel--and a coarsening temperature of 40 kelvin above that in UFG nickel.

PMID- 24136964
TI  - Electron-hole diffusion lengths exceeding 1 micrometer in an organometal
      trihalide perovskite absorber.
AB  - Organic-inorganic perovskites have shown promise as high-performance absorbers in
      solar cells, first as a coating on a mesoporous metal oxide scaffold and more
      recently as a solid layer in planar heterojunction architectures. Here, we report
      transient absorption and photoluminescence-quenching measurements to determine
      the electron-hole diffusion lengths, diffusion constants, and lifetimes in mixed
      halide (CH3NH3PbI(3-x)Cl(x)) and triiodide (CH3NH3PbI3) perovskite absorbers. We
      found that the diffusion lengths are greater than 1 micrometer in the mixed
      halide perovskite, which is an order of magnitude greater than the absorption
      depth. In contrast, the triiodide absorber has electron-hole diffusion lengths of
      ~100 nanometers. These results justify the high efficiency of planar
      heterojunction perovskite solar cells and identify a critical parameter to
      optimize for future perovskite absorber development.

PMID- 24136965
TI  - Long-range balanced electron- and hole-transport lengths in organic-inorganic
      CH3NH3PbI3.
AB  - Low-temperature solution-processed photovoltaics suffer from low efficiencies
      because of poor exciton or electron-hole diffusion lengths (typically about 10
      nanometers). Recent reports of highly efficient CH3NH3PbI3-based solar cells in a
      broad range of configurations raise a compelling case for understanding the
      fundamental photophysical mechanisms in these materials. By applying femtosecond
      transient optical spectroscopy to bilayers that interface this perovskite with
      either selective-electron or selective-hole extraction materials, we have
      uncovered concrete evidence of balanced long-range electron-hole diffusion
      lengths of at least 100 nanometers in solution-processed CH3NH3PbI3. The high
      photoconversion efficiencies of these systems stem from the comparable optical
      absorption length and charge-carrier diffusion lengths, transcending the
      traditional constraints of solution-processed semiconductors. 

PMID- 24136966
TI  - Genomically recoded organisms expand biological functions.
AB  - We describe the construction and characterization of a genomically recoded
      organism (GRO). We replaced all known UAG stop codons in Escherichia coli MG1655
      with synonymous UAA codons, which permitted the deletion of release factor 1 and
      reassignment of UAG translation function. This GRO exhibited improved properties
      for incorporation of nonstandard amino acids that expand the chemical diversity
      of proteins in vivo. The GRO also exhibited increased resistance to T7
      bacteriophage, demonstrating that new genetic codes could enable increased viral
      resistance. 

PMID- 24136967
TI  - Probing the limits of genetic recoding in essential genes.
AB  - Engineering radically altered genetic codes will allow for genomically recoded
      organisms that have expanded chemical capabilities and are isolated from nature.
      We have previously reassigned the translation function of the UAG stop codon;
      however, reassigning sense codons poses a greater challenge because such codons
      are more prevalent, and their usage regulates gene expression in ways that are
      difficult to predict. To assess the feasibility of radically altering the genetic
      code, we selected a panel of 42 highly expressed essential genes for
      modification. Across 80 Escherichia coli strains, we removed all instances of 13
      rare codons from these genes and attempted to shuffle all remaining codons. Our
      results suggest that the genome-wide removal of 13 codons is feasible; however,
      several genome design constraints were apparent, underscoring the importance of a
      strategy that rapidly prototypes and tests many designs in small pieces. 

PMID- 24136968
TI  - Rapid adaptation to climate facilitates range expansion of an invasive plant.
AB  - Adaptation to climate, evolving over contemporary time scales, could facilitate
      rapid range expansion across environmental gradients. Here, we examine local
      adaptation along a climatic gradient in the North American invasive plant Lythrum
      salicaria. We show that the evolution of earlier flowering is adaptive at the
      northern invasion front where it increases fitness as much as, or more than, the
      effects of enemy release and the evolution of increased competitive ability.
      However, early flowering decreases investment in vegetative growth, which reduces
      fitness by a factor of 3 in southern environments where the North American
      invasion commenced. Our results demonstrate that local adaptation can evolve
      quickly during range expansion, overcoming environmental constraints on propagule
      production. 

PMID- 24136969
TI  - The invasive chytrid fungus of amphibians paralyzes lymphocyte responses.
AB  - The chytrid fungus, Batrachochytrium dendrobatidis, causes chytridiomycosis and
      is a major contributor to global amphibian declines. Although amphibians have
      robust immune defenses, clearance of this pathogen is impaired. Because
      inhibition of host immunity is a common survival strategy of pathogenic fungi, we
      hypothesized that B. dendrobatidis evades clearance by inhibiting immune
      functions. We found that B. dendrobatidis cells and supernatants impaired
      lymphocyte proliferation and induced apoptosis; however, fungal recognition and
      phagocytosis by macrophages and neutrophils was not impaired. Fungal inhibitory
      factors were resistant to heat, acid, and protease. Their production was absent
      in zoospores and reduced by nikkomycin Z, suggesting that they may be components
      of the cell wall. Evasion of host immunity may explain why this pathogen has
      devastated amphibian populations worldwide. 

PMID- 24136970
TI  - Sleep drives metabolite clearance from the adult brain.
AB  - The conservation of sleep across all animal species suggests that sleep serves a
      vital function. We here report that sleep has a critical function in ensuring
      metabolic homeostasis. Using real-time assessments of tetramethylammonium
      diffusion and two-photon imaging in live mice, we show that natural sleep or
      anesthesia are associated with a 60% increase in the interstitial space,
      resulting in a striking increase in convective exchange of cerebrospinal fluid
      with interstitial fluid. In turn, convective fluxes of interstitial fluid
      increased the rate of beta-amyloid clearance during sleep. Thus, the restorative
      function of sleep may be a consequence of the enhanced removal of potentially
      neurotoxic waste products that accumulate in the awake central nervous system. 

PMID- 24136972
TI  - Gene expression profiling of circulating natural killer cells in head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Natural killer (NK) cells are a major player of the innate immune
      system. Besides known risk factors for head and neck squamous cell carcinoma
      (HNSCC), impaired immune surveillance may as well lead to tumor manifestation.
      MATERIALS AND METHODS: In the present study, microarrays technologies were
      employed in order to perform gene expression profiling of NK cells in HNSCC
      patients. Differentially expressed genes have been detected in a comparative
      setting consisting of non-treated HNSCC patients, treated recurrence-free HNSCC
      patients and healthy control subjects. RESULTS: Cytokine receptors such as CCR7,
      IL-7R, and CXCR3 were down-regulated in non-treated HNSCC patients compared to
      healthy subjects, indicating impaired immune surveillance. In treated patients,
      up-regulated genes such as receptors for Fc fragments of specific antibodies, or
      ficolin-1 can be withheld as an immunological response to tumor manifestation.
      CONCLUSION: This study provides insights into gene expression changes in NK cells
      of HNSCC dependent upon clinical status and introduces several candidate genes
      suitable for further investigation.

PMID- 24136971
TI  - Hyperdominance in the Amazonian tree flora.
AB  - The vast extent of the Amazon Basin has historically restricted the study of its
      tree communities to the local and regional scales. Here, we provide empirical
      data on the commonness, rarity, and richness of lowland tree species across the
      entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in
      all major forest types. Extrapolations suggest that Amazonia harbors roughly
      16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most
      of these are habitat specialists and only dominant in one or two regions of the
      basin. We discuss some implications of the finding that a small group of species-
      less diverse than the North American tree flora--accounts for half of the world's
      most diverse tree community.

PMID- 24136973
TI  - Genotoxic effect of two bleaching agents on oral mucosa.
AB  - AIM: To analyze the genotoxic effect of two hydrogen peroxide-containing
      bleaching products on oral mucosal cells. MATERIALS AND METHODS: The research was
      conducted on 22 individuals divided into two groups. Group 1 used ZOOM2 and group
      2 the Opalescence BOOST bleaching agent. Specimens of the gingival and the upper
      lip mucosa were obtained before, immediately after, and 72 h after the bleaching
      procedure and were analyzed using a micronucleus test. RESULTS: Seventy-two hours
      after bleaching treatment with BOOST, samples collected from the oral mucosa
      exhibited a statistically significant increase of all genotoxicity markers, with
      large effect sizes (Cohen's d>0.8) observed in the total number of micronuclei
      (MN), number of cells with 3+ MN, karyolysis and bi-nuclear cells. ZOOM2
      treatment showed a significant increase, with medium-to-large effect sizes, in
      the number of cells with 1 MN, karyolysis, nuclear buds and bi-nuclear cells.
      CONCLUSION: Both preparations demonstrated potential genotoxic effects.

PMID- 24136974
TI  - SHOX2 DNA methylation is a tumour marker in pleural effusions.
AB  - BACKGROUND: The published sensitivity of cytological examination for malignant
      pleural effusions (MPE) ranges between 50% and 71%. The Epi proLung(r) BL Reflex
      Assay (Epigenomics AG, Berlin, Germany) has been reported as being highly
      sensitive and specific for lung cancer using bronchial aspirates. We hypothesize
      the assay to be of use in the detection of MPE. MATERIALS AND METHODS: To test
      our hypothesis, we performed a retrospective cohort study on pleural effusion
      specimens of 1,270 patients (472 cases and 798 controls). The assay is based on
      quantification of methylated Short Stature Homeobox gene two (SHOX2) DNA in the
      specimen measured via multiplex real-time Polymerase Chain Reaction (PCR) on
      bisulfite-converted DNA. RESULTS: Surprisingly, the assay detects metastases of
      lung cancer, as well as metastases of other malignant tumours. With a re-defined
      cut-off criterion, the test achieved a sensitivity of 39.5% with a specificity of
      96.2%. CONCLUSION: This assay is able to detect MPE while not limited to the
      detection of lung cancer.

PMID- 24136975
TI  - The influence of Selol on the expression of oxidative stress genes in normal and
      malignant prostate cells.
AB  - Selol is a mixture of selenitriglycerides, obtained by the chemical modification
      of sunflower oil, which contain selenium at the +4 oxidation state. The aim of
      the present study was to describe the changes in the expression of genes related
      to oxidative stress caused by Selol in prostate cells: both normal (PNT1A) and
      malignant (LNCaP). The changes in gene expression in PNT1A and LNCaP cell lines
      under the influence of Selol were measured using a 96-well RT(2) Profiler TMPCR
      Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes
      functionally involved in the cellular oxidative stress response. Based on the
      obtained data, LNCaP cells exhibited a significantly lower potential for
      antioxidant defence when compared to PNT1A cells. The response of the malignant
      LNCaP cells to exposure to Selol was significantly different from that of the
      normal PNT1A cells, especially after 48 h of incubation. In the case of LNCaP
      cells, Selol causes down-regulation of the expression of many vital genes. Under
      in vitro conditions, the efficacy of Selol slightly changes with increasing
      concentration, but significantly increases when the incubation time is
      lengthened. 

PMID- 24136976
TI  - Serum and tissue metabolomics of head and neck cancer.
AB  - BACKGROUND: No reliable clinical markers to diagnose early stage-disease and
      predict its prognosis have yet been found for squamous cell carcinoma of the head
      and neck (HNSCC). MATERIALS AND METHODS: In the present study, the metabolomic
      analysis of serum and tissue samples obtained from patients with HNSCC was
      performed using gas chromatography/mass spectrometry. RESULTS: In serum, levels
      of several metabolites related to the glycolytic pathway, such as glucose, were
      higher in patients with HNSCC, and the levels of several amino acids were lower.
      In contrast to sera, the levels of many metabolites related to the glycolytic
      pathway appeared to be lower in tumor tissues of HNSCC than in non-tumorous
      tissues, and the levels of several amino acids, such as valine, thyrosine, serine
      and methionine, were higher. CONCLUSION: Our results demonstrate that changes in
      metabolite patterns are useful in assessing the clinical characteristics of
      HNSCC, and will hopefully lead to the establishment of novel diagnostic tools.

PMID- 24136983
TI  - Prominent hypointense veins on susceptibility weighted image in the cat brain
      with acute infarction: DWI, SWI, and PWI.
AB  - BACKGROUND: The multiple prominent hypointense veins on susceptibility-weighted
      imaging (SWI) have been found in the ischemic territory of patients with acute
      ischemic stroke. Venous side is the unknown area in the hemodynamics of brain
      infarction. PURPOSE: To evaluate the venous aspect in acute brain infarction
      through an animal study. MATERIAL AND METHODS: The acute infarction in cat brains
      was induced with a bolus infusion of 0.25 mL of triolein through one side of the
      common carotid artery. The magnetic resonance (MR) images, including diffusion
      weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and
      perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n
      = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were
      evaluated qualitatively and quantitatively. For qualitative assessment, the
      signal intensity of the serial MR images was evaluated. The presence or absence
      and the location with serial changes of infarction were identified on DWI and ADC
      map images. The presence or absence of prominent hypointense veins and the serial
      changes of cortical veins were also evaluated on SWI. Quantitative assessment was
      performed by comparing the relative cerebral blood volume (rCBV), cerebral blood
      flow (rCBF), and mean transit times (MTT) of the lesions with those of the
      contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF,
      and MTT ratio were also evaluated. RESULTS: Acute infarction in the first and
      second medial gyrus of lesion hemisphere was found by qualitative evaluation of
      DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of
      cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The
      hemorrhage transformation and prominent hypointense veins were seen at 4 days on
      SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV
      and rCBF ratios on PWIs in the acute infarction of cat brain. CONCLUSION: The
      prominent hypointense veins on SWI were seen in the half of the acute infarction
      at 4 days. The prominent hypointense veins on SWI may have good agreement with
      the increased MTT ratio.

PMID- 24136984
TI  - Relationship between cerebrospinal fluid flow, ventricles morphology, and DTI
      properties in internal capsules: differences between Alzheimer's disease and
      normal-pressure hydrocephalus.
AB  - BACKGROUND: Normal-pressure hydrocephalus (NPH) and Alzheimer's disease (AD) have
      some similar clinical features and both involve white matter and cerebrospinal
      fluid (CSF) disorders. PURPOSE: To compare putative relationships between
      ventricular morphology, CSF flow, and white matter diffusion in AD and NPH.
      MATERIAL AND METHODS: Thirty patients (18 with AD and 12 with suspected NPH) were
      included in the study. All patients underwent a 3-Tesla MRI scan, which included
      phase-contrast MRI of the aqueduct (to assess the aqueductal CSF stroke volume)
      and a DTI session (to calculate the fractional anisotropy [FA] and apparent
      diffusion coefficient [ADC]) in the internal capsules). RESULTS: FA was
      correlated with ventricular volume in the suspected NPH population (P < 0.001; rs
      = 0.88), whereas the ADC was highly correlated with the aqueductal CSF stroke
      volume in AD (P < 0.001; rs = 0.79). CONCLUSION: Although AD and NPH both involve
      CSF disorders, the two diseases do not have the same impact on the internal
      capsules. The magnitude of the ADC is related to the aqueductal CSF stroke volume
      in AD, whereas FA is related to ventricular volume in NPH.

PMID- 24136985
TI  - The usefulness of the oblique coronal plane in knee MRI on the evaluation of the
      posterior cruciate ligament.
AB  - BACKGROUND: Imaging findings of posterior cruciate ligament (PCL) injury may be
      equivocal, particularly when the patient has suffered a partial ligament tear.
      Some PCLs are positioned more horizontally, making it difficult to diagnose
      injury based on routine imaging planes alone due to partial volume artifact.
      PURPOSE: To evaluate the diagnostic accuracy of combining oblique coronal imaging
      (PCL view) with traditional orthogonal views for PCL evaluation. MATERIAL AND
      METHODS: This retrospective study included 20 patients with PCL injury and 43
      patients with intact PCL who underwent PCL view imaging. Anatomic identification
      of PCL pathology on the orthogonal magnetic resonance imaging (MRI) sequences and
      PCL views was evaluated. Subjective scoring of the PCL was performed by two
      radiologists who assessed the possibility of a PCL tear based on an entire length
      view, an entire width view, and margin sharpness according to a 4-point scale.
      Diagnostic accuracy using these two views was evaluated by calculating the
      sensitivity, specificity, and accuracy. Arthroscopic and clinical findings were
      used as the reference standard. RESULTS: Total scores for the PCL view were
      higher than those of orthogonal views (P < 0.001). Both readers found that
      anatomic identification using the full width view and sharp margin to be superior
      using the PCL view compared with the orthogonal views (P < 0.001). The
      specificities and accuracies were higher in cases where an additional PCL view
      was provided, but did not show statistical significance. CONCLUSION: PCL view
      provides better anatomic evaluation of the PCL and mild improvement in the
      specificity and accuracy.

PMID- 24136989
TI  - Understanding employment barriers among older Korean immigrants.
AB  - PURPOSE OF THE STUDY: This study involved an in-depth exploration of the
      employment barriers of older Korean immigrants in Los Angeles. DESIGN AND
      METHODS: This qualitative study used data obtained from 6 focus groups and 5
      individual interviews. Participants were 36 older Korean immigrants living in Los
      Angeles, aged 50 years and older, and either unemployed or employed in part-time
      or full-time work. A grounded theory analytical approach and constant comparison
      method were used. RESULTS: Ten major themes emerged as employment barriers for
      older Korean immigrants and were categorized as stereotype, human capital, and
      acculturation barriers. Ageism among employers specific to Korean culture, lack
      of English proficiency, separation from U.S. culture, marginalization from both
      Korean and U.S. cultures, and lack of social networks were important themes. In
      addition, older Korean immigrants experienced multiple interconnected barriers.
      IMPLICATIONS: The findings highlight the importance of using a multidimensional
      approach to explore employment barriers among older Korean immigrants who face
      multiple obstacles in finding jobs. Implications for local governments and Korean
      communities and potential services to support employment opportunities for older
      Korean immigrants are discussed.

PMID- 24136990
TI  - Live-In Versus Live-Out Home Care in Israel: Satisfaction With Services and
      Caregivers' Outcomes.
AB  - PURPOSE OF THE STUDY: The present study provides a preliminary examination of the
      relationship between the type of home care services (live-in vs. live-out; i.e.,
      round the clock vs. several hours per week), the caregiver's satisfaction with
      services, and the caregiver's burden, distress, well-being, and subjective health
      status within the conceptual framework of caregiving outcomes proposed by Yates
      and colleagues (Yates, M. E., Tennstedt, S., & Chang, B. H. [1999]. Contributors
      to and mediators of psychological well-being for informal caregivers. Journal of
      Gerontology: Psychological Sciences, 54, P12 -P22. doi:10.1093/geronb/54B.1.P12).
      DESIGN AND METHODS: A random stratified sample of family caregivers of older
      adults more than the age of 70 who receive live-in (442) or live-out (244) home
      care services through the financial assistance of the National Insurance
      institute of Israel was selected. A path analysis was conducted. RESULTS:
      Satisfaction with services was higher among caregivers under the live-in home
      care arrangement and positively related to well-being. Among caregivers, live-in
      home care was directly associated with higher levels of subjective health and
      indirectly associated with better well-being via satisfaction with services.
      IMPLICATIONS: The present study emphasizes the potential benefits of live-in home
      care services for caregivers of older adults who suffer from high levels of
      impairment and the importance of assessing satisfaction with services as a
      predictor of caregivers' outcomes.

PMID- 24136991
TI  - Untapped richness in Erik H. Erikson's rootstock.
AB  - Erik H. Erikson published his groundbreaking theory of 8 stages of lifelong
      psychosocial development in 1950. His theory expanded psychoanalytic concepts of
      psychosexual development to include the importance of social dynamics; it
      transcended then-current thinking that psychological development culminated in
      early adulthood, acknowledging that systematic human development continues
      throughout the entire life cycle. The theory made Erikson a pioneer in
      developmental psychology. His last authored book, Vital Involvement in Old Age,
      rearticulated and elaborated 3 principles that, in different words, are rooted in
      his original theory of healthy life cycle development: (1) Dynamic Balance of
      Opposites; (2) Vital Involvement; and (3) Life in Time. Using a lens informed by
      knowledge gained over the past 30 years and by reflections of one of the original
      researchers on that project, the current manuscript seeks to spark new interest
      in Erikson's late-life contribution. It explains the principles in new detail,
      links them to relevant research, and suggests ways they could enable Erikson's
      ideas to further enrich gerontological practice and research. 

PMID- 24136988
TI  - The molecular balancing act of p16(INK4a) in cancer and aging.
AB  - p16(INK4a), located on chromosome 9p21.3, is lost among a cluster of neighboring
      tumor suppressor genes. Although it is classically known for its capacity to
      inhibit cyclin-dependent kinase (CDK) activity, p16(INK4a) is not just a one
      trick pony. Long-term p16(INK4a) expression pushes cells to enter senescence, an
      irreversible cell-cycle arrest that precludes the growth of would-be cancer cells
      but also contributes to cellular aging. Importantly, loss of p16(INK4a) is one of
      the most frequent events in human tumors and allows precancerous lesions to
      bypass senescence. Therefore, precise regulation of p16(INK4a) is essential to
      tissue homeostasis, maintaining a coordinated balance between tumor suppression
      and aging. This review outlines the molecular pathways critical for proper
      p16(INK4a) regulation and emphasizes the indispensable functions of p16(INK4a) in
      cancer, aging, and human physiology that make this gene special.

PMID- 24136992
TI  - Na+/H+ exchanger 1 is regulated via its lipid-interacting domain, which functions
      as a molecular switch: a pharmacological approach using indolocarbazole
      compounds.
AB  - The plasma membrane Na(+)/H(+) exchanger 1 (NHE1) is rapidly activated in
      response to various stimuli. The membrane-proximal cytoplasmic region (~60
      residues), termed the lipid-interacting domain (LID), is an important regulatory
      domain of NHE1. Here, we used a pharmacological approach to further characterize
      the role of LID in the regulation of NHE1. Pharmacological analysis using
      staurosporine-like indolocarbazole and bisindolylmaleimide compounds suggested
      that the phorbol ester- and receptor agonist-induced activation of NHE1 occurs
      through a protein kinase C-independent mechanism. In particular, only
      indolocarbazole compounds that inhibited NHE1 activation were able to interact
      with the LID, suggesting that the inhibition of NHE1 activation is achieved
      through the direct action of these compounds on the LID. Furthermore, in addition
      to phorbol esters and a receptor agonist, okadaic acid and hyperosmotic stress,
      which are known to activate NHE1 through unknown mechanisms, were found to
      promote membrane association of the LID concomitant with NHE1 activation; these
      effects were inhibited by staurosporine, as well as by a mutation in the LID.
      Binding experiments using the fluorescent ATP analog trinitrophenyl ATP revealed
      that ATP and the NHE1 activator phosphatidylinositol 4,5-bisphosphate bind
      competitively to the LID. These findings suggest that modulation of NHE1 activity
      by various activators and inhibitors occurs through the direct binding of these
      molecules to the LID, which alters the association of the LID with the plasma
      membrane. 

PMID- 24136993
TI  - Role of JunB in adenosine A2B receptor-mediated vascular endothelial growth
      factor production.
AB  - Interstitial adenosine stimulates neovascularization in part through A2B
      adenosine receptor-dependent upregulation of vascular endothelial growth factor
      (VEGF). In the current study, we tested the hypothesis that A2B receptors
      upregulate JunB, which can contribute to stimulation of VEGF production. Using
      the human microvascular endothelial cell line, human mast cell line, mouse
      cardiac Sca1-positive stromal cells, and mouse Lewis lung carcinoma (LLC) cells,
      we found that adenosine receptor-dependent upregulation of VEGF production was
      associated with an increase in VEGF transcription, activator protein-1 (AP-1)
      activity, and JunB accumulation in all cells investigated. Furthermore, the
      expression of JunB, but not the expression of other genes encoding transcription
      factors from the Jun family, was specifically upregulated. In LLC cells
      expressing A2A and A2B receptor transcripts, only the nonselective adenosine
      agonist NECA (5'-N-ethylcarboxamidoadenosine), but not the selective A2A receptor
      agonist CGS21680 [2-p-(2-carboxyethyl) phenylethylamino-5'-N
      ethylcarboxamidoadenosine], significantly increased JunB reporter activity and
      JunB nuclear accumulation, which were inhibited by the A2B receptor antagonist
      PSB603 [(8-[4-[4-((4-chlorophenzyl)piperazide-1-sulfonyl)phenyl]]-1
      propylxanthine]. Using activators and inhibitors of intracellular signaling, we
      demonstrated that A2B receptor-dependent accumulation of JunB protein and VEGF
      secretion share common intracellular pathways. NECA enhanced JunB binding to the
      murine VEGF promoter, whereas mutation of the high-affinity AP-1 site (-1093 to 
      1086) resulted in a loss of NECA-dependent VEGF reporter activity. Finally, NECA
      dependent VEGF secretion and reporter activity were inhibited by the expression
      of a dominant negative JunB or by JunB knockdown. Thus, our data suggest an
      important role of the A2B receptor-dependent upregulation of JunB in VEGF
      production and possibly other AP-1-regulated events. 

PMID- 24136994
TI  - Validation of freezing tissues and cells for analysis of DNA strand break levels
      by comet assay.
AB  - The comet analysis of DNA strand break levels in tissues and cells has become a
      common method of screening for genotoxicity. The large majority of published
      studies have used fresh tissues and cells processed immediately after collection.
      However, we have used frozen tissues and cells for more than 10 years, and we
      believe that freezing samples improve efficiency of the method. We compared DNA
      strand break levels measured in fresh and frozen bronchoalveolar cells, and lung
      and liver tissues from mice exposed to the known mutagen methyl methanesulphonate
      (0, 25, 75, 112.5mg/kg). We used a high-throughput comet protocol with fully
      automated scoring of DNA strand break levels. The overall results from fresh and
      frozen samples were in agreement [R (2) = 0.93 for %DNA in tail (%TDNA) and R (2)
      = 0.78 for tail length (TL)]. A slightly increased %TDNA was observed in lung and
      liver tissue from vehicle controls; and TL was slightly reduced in
      bronchoalveolar lavage cells from the high-dose group. In our comet protocol, a
      small block of tissue designated for comet analysis is frozen immediately at
      tissue collection and kept deep frozen until rapidly homogenised and embedded in
      agarose. To demonstrate the feasibility of long-term freezing of samples, we
      analysed the day-to-day variation of our internal historical negative and
      positive comet assay controls collected over a 10-year period (1128 observations,
      11 batches of frozen untreated and H2O2-treated A549 lung epithelial cells). The
      H2O2 treatment explained most of the variation 57-77% and the day-to-day
      variation was only 2-12%. The presented protocol allows analysis of samples
      collected over longer time span, at different locations, with reduced variation
      by reducing number of electrophoreses and is suitable for both toxicological and
      epidemiological studies. The use of frozen tissues; however, requires great care
      during preparation before analysis, with handling as a major risk factor. 

PMID- 24136995
TI  - Approaches to salivary cortisol collection and analysis in infants.
AB  - Salivary cortisol is becoming more commonly utilized as a biologic marker of
      stress in observational studies and intervention research. However, its use with
      infants (12 months of age or younger) is less widespread and poses some special
      challenges to researchers. In order to decide on the most suitable collection
      procedure for salivary cortisol in infants, a number of criteria should be
      considered. This article will aid investigators interested in integrating
      salivary cortisol measurement into their research studies by presenting (1) an
      overview of the patterns of cortisol secretion in infancy including the
      development of diurnal rhythm and response to stress; (2) a comparison of the
      most commonly used approaches for collecting salivary cortisol samples in infants
      including cotton rope, syringe aspiration technique, filter paper, hydrocellulose
      microsponge, and the Salimetrics children's swab; (3) a discussion of the factors
      contributing to heightened cortisol variability in infancy and how these can be
      limited; (4) analytical issues associated with cortisol measurement; and (5)
      examples of criteria to consider when choosing a saliva sampling method and lab
      for conducting assays. 

PMID- 24136996
TI  - Quench the thirst: lessons from clinical thirst trials.
AB  - Thirst, as a symptom, has long been considered the most prevalent clinical
      complaint patients voice in healthcare settings. Yet, rarely have researchers
      examined thirst by its correlation with physiologic factors. This review was
      undertaken to examine the relationships between thirst ratings and factors
      mediating its primary physiologic correlates: plasma osmolality (pOsm) and
      arginine vasopressin peptide (AVP). A literature search was undertaken to
      identify clinical studies in human subjects that investigated the relationship of
      thirst to specific physiologic thirst-related correlates and associated thirst
      mediators. Thirst was induced in 17 selected clinical studies by hyperosmolar
      infusion, through water deprivation or exercise weight-loss regimens. Positive
      linear relationships between the subjects' thirst ratings and rising serum pOsm
      levels confirmed the presence of intact osmotic thirst drives. However, there
      were significant variations in normal compensatory rises in AVP levels that
      followed the rises in plasma osmolality after the subjects were exposed to cold,
      physical pre-conditioning and water immersion tests. Notably, older adults in the
      studies reported diminished thirst ratings. Weak correlations suggest that
      angiotensin II may play only a minor role in thirst mediation. Atrial natriuretic
      hormone's inhibitory effect on thirst was inconsistent. Findings indicated that
      older adults are at higher risk for profound dehydration due to sensory deficits
      along with failure to correct volume losses. The thirst trials results support
      the close correlation between serum pOsm values and patients' thirst ratings,
      with the exception of the older adult. 

PMID- 24136997
TI  - IMG/M 4 version of the integrated metagenome comparative analysis system.
AB  - IMG/M (http://img.jgi.doe.gov/m) provides support for comparative analysis of
      microbial community aggregate genomes (metagenomes) in the context of a
      comprehensive set of reference genomes from all three domains of life, as well as
      plasmids, viruses and genome fragments. IMG/M's data content and analytical tools
      have expanded continuously since its first version was released in 2007. Since
      the last report published in the 2012 NAR Database Issue, IMG/M's database
      architecture, annotation and data integration pipelines and analysis tools have
      been extended to copewith the rapid growth in the number and size of metagenome
      data sets handled by the system. IMG/M data marts provide support for the
      analysis of publicly available genomes, expert review of metagenome annotations
      (IMG/M ER: http://img.jgi.doe.gov/mer) and Human Microbiome Project (HMP)
      specific metagenome samples (IMG/M HMP: http://img.jgi.doe.gov/imgm_hmp). 

PMID- 24136998
TI  - Soybean knowledge base (SoyKB): a web resource for integration of soybean
      translational genomics and molecular breeding.
AB  - Soybean Knowledge Base (http://soykb.org) is a comprehensive web resource
      developed for bridging soybean translational genomics and molecular breeding
      research. It provides information for six entities including genes/proteins,
      microRNAs/sRNAs, metabolites, single nucleotide polymorphisms, plant introduction
      lines and traits. It also incorporates many multi-omics datasets including
      transcriptomics, proteomics, metabolomics and molecular breeding data, such as
      quantitative trait loci, traits and germplasm information. Soybean Knowledge Base
      has a new suite of tools such as In Silico Breeding Program for soybean breeding,
      which includes a graphical chromosome visualizer for ease of navigation. It
      integrates quantitative trait loci, traits and germplasm information along with
      genomic variation data, such as single nucleotide polymorphisms, insertions,
      deletions and genome-wide association studies data, from multiple soybean
      cultivars and Glycine soja. 

PMID- 24137000
TI  - Updates of the HbVar database of human hemoglobin variants and thalassemia
      mutations.
AB  - HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated
      locus-specific databases launched in 2001 by a multi-center academic effort to
      provide timely information on the genomic alterations leading to hemoglobin
      variants and all types of thalassemia and hemoglobinopathies. Database records
      include extensive phenotypic descriptions, biochemical and hematological effects,
      associated pathology and ethnic occurrence, accompanied by mutation frequencies
      and references. Here, we report updates to >600 HbVar entries, inclusion of
      population-specific data for 28 populations and 27 ethnic groups for alpha-, and
      beta-thalassemias and additional querying options in the HbVar query page. HbVar
      content was also inter-connected with two other established genetic databases,
      namely FINDbase (http://www.findbase.org) and Leiden Open-Access Variation
      database (http://www.lovd.nl), which allows comparative data querying and
      analysis. HbVar data content has contributed to the realization of two
      collaborative projects to identify genomic variants that lie on different globin
      paralogs. Most importantly, HbVar data content has contributed to demonstrate the
      microattribution concept in practice. These updates significantly enriched the
      database content and querying potential, enhanced the database profile and data
      quality and broadened the inter-relation of HbVar with other databases, which
      should increase the already high impact of this resource to the globin and
      genetic database community. 

PMID- 24136999
TI  - RiceWiki: a wiki-based database for community curation of rice genes.
AB  - Rice is the most important staple food for a large part of the world's human
      population and also a key model organism for biological studies of crops as well
      as other related plants. Here we present RiceWiki (http://ricewiki.big.ac.cn), a
      wiki-based, publicly editable and open-content platform for community curation of
      rice genes. Most existing related biological databases are based on expert
      curation; with the exponentially exploding volume of rice knowledge and other
      relevant data, however, expert curation becomes increasingly laborious and time
      consuming to keep knowledge up-to-date, accurate and comprehensive, struggling
      with the flood of data and requiring a large number of people getting involved in
      rice knowledge curation. Unlike extant relevant databases, RiceWiki features
      harnessing collective intelligence in community curation of rice genes,
      quantifying users' contributions in each curated gene and providing explicit
      authorship for each contributor in any given gene, with the aim to exploit the
      full potential of the scientific community for rice knowledge curation. Based on
      community curation, RiceWiki bears the potential to make it possible to build a
      rice encyclopedia by and for the scientific community that harnesses community
      intelligence for collaborative knowledge curation, covers all aspects of
      biological knowledge and keeps evolving with novel knowledge. 

PMID- 24137001
TI  - The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to
      regulate gene expression in the heart.
AB  - The Polycomb-group protein, Ezh2, is required for epigenetic gene silencing in
      the adult heart by unknown mechanism. We investigated the role of Ezh2 and non
      coding RNAs in a mouse model of pressure overload using transverse aortic
      constriction (TAC) attenuated by the prototypical histone deacetylase inhibitor,
      trichostatin A (TSA). Chromatin immunoprecipitation of TAC and TAC+TSA hearts
      suggests interaction of Ezh2 and primary microRNA-208b (pri-miR-208b) in the
      regulation of hypertrophic gene expression. RNAi silencing of pri-miR-208b and
      Ezh2 validate pri-miR-208b-mediated transcriptional silencing of genes implicated
      in cardiac hypertrophy including the suppression of the bi-directional promoter
      (bdP) of the cardiac myosin heavy chain genes. In TAC mouse heart, TSA attenuated
      Ezh2 binding to bdP and restored antisense beta-MHC and alpha-MHC gene
      expression. RNA-chromatin immunoprecipitation experiments in TAC hearts also show
      increased pri-miR-208b dependent-chromatin binding. These results are the first
      description by which primary miR interactions serve to integrate chromatin
      modifications and the transcriptional response to distinct signaling cues in the
      heart. These studies provide a framework for MHC expression and regulation of
      genes implicated in pathological remodeling of ventricular hypertrophy. 

PMID- 24137002
TI  - Systematic identification of transcriptional regulatory modules from protein
      protein interaction networks.
AB  - Transcription factors (TFs) combine with co-factors to form transcriptional
      regulatory modules (TRMs) that regulate gene expression programs with
      spatiotemporal specificity. Here we present a novel and generic method (rTRM) for
      the reconstruction of TRMs that integrates genomic information from TF binding,
      cell type-specific gene expression and protein-protein interactions. rTRM was
      applied to reconstruct the TRMs specific for embryonic stem cells (ESC) and
      hematopoietic stem cells (HSC), neural progenitor cells, trophoblast stem cells
      and distinct types of terminally differentiated CD4(+) T cells. The ESC and HSC
      TRM predictions were highly precise, yielding 77 and 96 proteins, of which ~75%
      have been independently shown to be involved in the regulation of these cell
      types. Furthermore, rTRM successfully identified a large number of bridging
      proteins with known roles in ESCs and HSCs, which could not have been identified
      using genomic approaches alone, as they lack the ability to bind specific DNA
      sequences. This highlights the advantage of rTRM over other methods that ignore
      PPI information, as proteins need to interact with other proteins to form
      complexes and perform specific functions. The prediction and experimental
      validation of the co-factors that endow master regulatory TFs with the capacity
      to select specific genomic sites, modulate the local epigenetic profile and
      integrate multiple signals will provide important mechanistic insights not only
      into how such TFs operate, but also into abnormal transcriptional states leading
      to disease. 

PMID- 24137003
TI  - High-resolution characterization of CPD hotspot formation in human fibroblasts.
AB  - Repair of DNA lesions must occur within the chromatin landscape and is associated
      with alterations in histone modifications and nucleosome rearrangement. To
      directly associate these chromatin features with DNA damage and repair, it is
      necessary to be able to map DNA adducts. We have developed a cyclobutane
      pyrimidine dimer (CPD)-specific immunoprecipitation method and mapped ultraviolet
      damage hotspots across human chromosomes 1 and 6. CPD hotspots occur almost
      equally in genic and intergenic regions. However, these hotspots are
      significantly more prevalent adjacent to repeat elements, especially Alu repeats.
      Nucleosome mapping studies indicate that nucleosomes are consistently positioned
      at Alu elements where CPD hotspots form, but by 2 h post-irradiation, these same
      regions are significantly depleted of nucleosomes. These results indicate that
      nucleosomes associated with hotspots of CPD formation are readily rearranged,
      potentially making them accessible to DNA repair machinery. Our results represent
      the first chromosome scale map of ultraviolet-induced DNA lesions in the human
      genome, and reveal the sequence features and dynamic chromatin changes associated
      with CPD hotspots. 

PMID- 24137004
TI  - Interactions of the TnaC nascent peptide with rRNA in the exit tunnel enable the
      ribosome to respond to free tryptophan.
AB  - A transcriptional attenuation mechanism regulates expression of the bacterial
      tnaCAB operon. This mechanism requires ribosomal arrest induced by the regulatory
      nascent TnaC peptide in response to free L-tryptophan (L-Trp). In this study we
      demonstrate, using genetic and biochemical analyses, that in Escherichia coli,
      TnaC residue I19 and 23S rRNA nucleotide A2058 are essential for the ribosome's
      ability to sense free L-Trp. We show that the mutational change A2058U in 23S
      rRNA reduces the concentration dependence of L-Trp-mediated tna operon induction,
      whereas the TnaC I19L change suppresses this phenotype, restoring the sensitivity
      of the translating A2058U mutant ribosome to free L-Trp. These findings suggest
      that interactions between TnaC residue I19 and 23S rRNA nucleotide A2058
      contribute to the creation of a regulatory L-Trp binding site within the
      translating ribosome. 

PMID- 24137005
TI  - High-copy bacterial plasmids diffuse in the nucleoid-free space, replicate
      stochastically and are randomly partitioned at cell division.
AB  - Bacterial plasmids play important roles in the metabolism, pathogenesis and
      bacterial evolution and are highly versatile biotechnological tools. Stable
      inheritance of plasmids depends on their autonomous replication and efficient
      partition to daughter cells at cell division. Active partition systems have not
      been identified for high-copy number plasmids, and it has been generally believed
      that they are partitioned randomly at cell division. Nevertheless, direct
      evidence for the cellular location of replicating and nonreplicating plasmids,
      and the partition mechanism has been lacking. We used as model pJHCMW1, a plasmid
      isolated from Klebsiella pneumoniae that includes two beta-lactamase and two
      aminoglycoside resistance genes. Here we report that individual ColE1-type
      plasmid molecules are mobile and tend to be excluded from the nucleoid, mainly
      localizing at the cell poles but occasionally moving between poles along the long
      axis of the cell. As a consequence, at the moment of cell division, most plasmid
      molecules are located at the poles, resulting in efficient random partition to
      the daughter cells. Complete replication of individual molecules occurred
      stochastically and independently in the nucleoid-free space throughout the cell
      cycle, with a constant probability of initiation per plasmid. 

PMID- 24137006
TI  - The SERRATE protein is involved in alternative splicing in Arabidopsis thaliana.
AB  - How alternative splicing (AS) is regulated in plants has not yet been elucidated.
      Previously, we have shown that the nuclear cap-binding protein complex (AtCBC) is
      involved in AS in Arabidopsis thaliana. Here we show that both subunits of AtCBC
      (AtCBP20 and AtCBP80) interact with SERRATE (AtSE), a protein involved in the
      microRNA biogenesis pathway. Moreover, using a high-resolution reverse
      transcriptase-polymerase chain reaction AS system we have found that AtSE
      influences AS in a similar way to the cap-binding complex (CBC), preferentially
      affecting selection of 5' splice site of first introns. The AtSE protein acts in
      cooperation with AtCBC: many changes observed in the mutant lacking the correct
      SERRATE activity were common to those observed in the cbp mutants. Interestingly,
      significant changes in AS of some genes were also observed in other mutants of
      plant microRNA biogenesis pathway, hyl1-2 and dcl1-7, but a majority of them did
      not correspond to the changes observed in the se-1 mutant. Thus, the role of
      SERRATE in AS regulation is distinct from that of HYL1 and DCL1, and is similar
      to the regulation of AS in which CBC is involved. 

PMID- 24137007
TI  - Scanning fluorescence correlation spectroscopy techniques to quantify the
      kinetics of DNA double strand break repair proteins after gamma-irradiation and
      bleomycin treatment.
AB  - A common feature of DNA repair proteins is their mobilization in response to DNA
      damage. The ability to visualizing and quantifying the kinetics of proteins
      localizing/dissociating from DNA double strand breaks (DSBs) via
      immunofluorescence or live cell fluorescence microscopy have been powerful tools
      in allowing insight into the DNA damage response, but these tools have some
      limitations. For example, a number of well-established DSB repair factors, in
      particular those required for non-homologous end joining (NHEJ), do not form
      discrete foci in response to DSBs induced by ionizing radiation (IR) or
      radiomimetic drugs, including bleomycin, in living cells. In this report, we show
      that time-dependent kinetics of the NHEJ factors Ku80 and DNA-dependent protein
      kinase catalytic subunits (DNA-PKcs) in response to IR and bleomycin can be
      quantified by Number and Brightness analysis and Raster-scan Image Correlation
      Spectroscopy. Fluorescent-tagged Ku80 and DNA-PKcs quickly mobilized in response
      to IR and bleomycin treatments consistent with prior reports using laser
      generated DSBs. The response was linearly dependent on IR dose, and blocking NHEJ
      enhanced immobilization of both Ku80 and DNA-PKcs after DNA damage. These
      findings support the idea of using Number and Brightness and Raster-scan Image
      Correlation Spectroscopy as methods to monitor kinetics of DSB repair proteins in
      living cells under conditions mimicking radiation and chemotherapy treatments. 

PMID- 24137008
TI  - HoPaCI-DB: host-Pseudomonas and Coxiella interaction database.
AB  - Bacterial infectious diseases are the result of multifactorial processes affected
      by the interplay between virulence factors and host targets. The host-Pseudomonas
      and Coxiella interaction database (HoPaCI-DB) is a publicly available manually
      curated integrative database (http://mips.helmholtz-muenchen.de/HoPaCI/) of host
      pathogen interaction data from Pseudomonas aeruginosa and Coxiella burnetii. The
      resource provides structured information on 3585 experimentally validated
      interactions between molecules, bioprocesses and cellular structures extracted
      from the scientific literature. Systematic annotation and interactive graphical
      representation of disease networks make HoPaCI-DB a versatile knowledge base for
      biologists and network biology approaches. 

PMID- 24137009
TI  - Targeted DNA methylation by homology-directed repair in mammalian cells.
      Transcription reshapes methylation on the repaired gene.
AB  - We report that homology-directed repair of a DNA double-strand break within a
      single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the
      methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1,
      DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are
      recruited to the site of repair and are responsible for selective methylation of
      the promoter-distal segment of the repaired DNA. The initial methylation pattern
      of the locus is modified in a transcription-dependent fashion during the 15-20
      days following repair, at which time no further changes in the methylation
      pattern occur. The variation in DNA modification generates stable clones with
      wide ranges of GFP expression. Collectively, our data indicate that somatic DNA
      methylation follows homologous repair and is subjected to remodeling by local
      transcription in a discrete time window during and after the damage. We propose
      that DNA methylation of repaired genes represents a DNA damage code and is source
      of variation of gene expression. 

PMID- 24137010
TI  - Discovery of functional genomic motifs in viruses with ViReMa-a Virus
      Recombination Mapper-for analysis of next-generation sequencing data.
AB  - We developed an algorithm named ViReMa (Viral-Recombination-Mapper) to provide a
      versatile platform for rapid, sensitive and nucleotide-resolution detection of
      recombination junctions in viral genomes using next-generation sequencing data.
      Rather than mapping read segments of pre-defined lengths and positions, ViReMa
      dynamically generates moving read segments. ViReMa initially attempts to align
      the 5' end of a read to the reference genome(s) with the Bowtie seed-based
      alignment. A new read segment is then made by either extracting any unaligned
      nucleotides at the 3' end of the read or by trimming the first nucleotide from
      the read. This continues iteratively until all portions of the read are either
      mapped or trimmed. With multiple reference genomes, it is possible to detect
      virus-to-host or inter-virus recombination. ViReMa is also capable of detecting
      insertion and substitution events and multiple recombination junctions within a
      single read. By mapping the distribution of recombination events in the genome of
      flock house virus, we demonstrate that this information can be used to discover
      de novo functional motifs located in conserved regions of the viral genome. 

PMID- 24137011
TI  - The ADAR RNA editing enzyme controls neuronal excitability in Drosophila
      melanogaster.
AB  - RNA editing by deamination of specific adenosine bases to inosines during pre
      mRNA processing generates edited isoforms of proteins. Recoding RNA editing is
      more widespread in Drosophila than in vertebrates. Editing levels rise strongly
      at metamorphosis, and Adar(5G1) null mutant flies lack editing events in hundreds
      of CNS transcripts; mutant flies have reduced viability, severely defective
      locomotion and age-dependent neurodegeneration. On the other hand, overexpressing
      an adult dADAR isoform with high enzymatic activity ubiquitously during larval
      and pupal stages is lethal. Advantage was taken of this to screen for genetic
      modifiers; Adar overexpression lethality is rescued by reduced dosage of the Rdl
      (Resistant to dieldrin), gene encoding a subunit of inhibitory GABA receptors.
      Reduced dosage of the Gad1 gene encoding the GABA synthetase also rescues Adar
      overexpression lethality. Drosophila Adar(5G1) mutant phenotypes are ameliorated
      by feeding GABA modulators. We demonstrate that neuronal excitability is linked
      to dADAR expression levels in individual neurons; Adar-overexpressing larval
      motor neurons show reduced excitability whereas Adar(5G1) null mutant or targeted
      Adar knockdown motor neurons exhibit increased excitability. GABA inhibitory
      signalling is impaired in human epileptic and autistic conditions, and vertebrate
      ADARs may have a relevant evolutionarily conserved control over neuronal
      excitability. 

PMID- 24137012
TI  - The Global Genome Biodiversity Network (GGBN) Data Portal.
AB  - The Global Genome Biodiversity Network (GGBN) was formed in 2011 with the
      principal aim of making high-quality well-documented and vouchered collections
      that store DNA or tissue samples of biodiversity, discoverable for research
      through a networked community of biodiversity repositories. This is achieved
      through the GGBN Data Portal (http://data.ggbn.org), which links globally
      distributed databases and bridges the gap between biodiversity repositories,
      sequence databases and research results. Advances in DNA extraction techniques
      combined with next-generation sequencing technologies provide new tools for
      genome sequencing. Many ambitious genome sequencing projects with the potential
      to revolutionize biodiversity research consider access to adequate samples to be
      a major bottleneck in their workflow. This is linked not only to accelerating
      biodiversity loss and demands to improve conservation efforts but also to a lack
      of standardized methods for providing access to genomic samples. Biodiversity
      biobank-holding institutions urgently need to set a standard of collaboration
      towards excellence in collections stewardship, information access and sharing and
      responsible and ethical use of such collections. GGBN meets these needs by
      enabling and supporting accessibility and the efficient coordinated expansion of
      biodiversity biobanks worldwide. 

PMID- 24137013
TI  - Renalase in hypertension and kidney disease.
AB  - Renalase, a recently discovered flavoprotein, which is strongly expressed in the
      kidney and heart, effectively metabolizes catecholamines. It was discovered
      during the search to identify proteins secreted by the kidney that could help
      explain the high incidence of cardiovascular disease in patients with chronic
      kidney disease. Recent advances have led to more detailed knowledge of its
      biology, structure, enzymatic activity, mechanisms of action, associations with
      human disease states and potential therapeutic value. In this study, we review
      these advances with a focus on hypertension and kidney disease. 

PMID- 24137014
TI  - Overweight and obesity among Hispanic children entering foster care: a
      preliminary examination of polyvictimization.
AB  - This retrospective medical chart review examined the prevalence of
      overweight/obesity (>=85th percentile) and obesity (>=95th percentile) in
      Hispanic foster children aged 2-18 years in Los Angeles, California. Logistic
      regression was used for boys and girls separately to analyze polyvictimization
      (i.e., one vs. two or more types of maltreatment), type of maltreatment (abuse
      vs. neglect), and age-group as risk factors for overweight and obesity. Almost
      40% of participants were overweight/obese, with the highest prevalence (47.7%)
      observed among children aged 12-18. Children aged 6-18 were at an increased risk
      of overweight/obesity and obesity compared with children aged 2-5. Although
      polyvictimization has been shown to have adverse health effects, in this study,
      it was related to slightly lower odds of obesity for boys but was unrelated to
      high weight for girls. Addressing the obesity epidemic among Hispanic foster
      children is vital to preventing continued obesity and the development of obesity
      related health problems, especially by focusing on important community and family
      influences. 

PMID- 24137015
TI  - CBTRUS statistical report: Primary brain and central nervous system tumors
      diagnosed in the United States in 2006-2010.

PMID- 24137017
TI  - Auditory distortions: origins and functions.
AB  - To enhance weak sounds while compressing the dynamic intensity range, auditory
      sensory cells amplify sound-induced vibrations in a nonlinear, intensity
      dependent manner. In the course of this process, instantaneous waveform
      distortion is produced, with two conspicuous kinds of interwoven consequences,
      the introduction of new sound frequencies absent from the original stimuli, which
      are audible and detectable in the ear canal as otoacoustic emissions, and the
      possibility for an interfering sound to suppress the response to a probe tone,
      thereby enhancing contrast among frequency components. We review how the diverse
      manifestations of auditory nonlinearity originate in the gating principle of
      their mechanoelectrical transduction channels; how they depend on the coordinated
      opening of these ion channels ensured by connecting elements; and their links to
      the dynamic behavior of auditory sensory cells. This paper also reviews how the
      complex properties of waves traveling through the cochlea shape the
      manifestations of auditory nonlinearity. Examination methods based on the
      detection of distortions open noninvasive windows on the modes of activity of
      mechanosensitive structures in auditory sensory cells and on the distribution of
      sites of nonlinearity along the cochlear tonotopic axis, helpful for deciphering
      cochlear molecular physiology in hearing-impaired animal models. Otoacoustic
      emissions enable fast tests of peripheral sound processing in patients. The study
      of auditory distortions also contributes to the understanding of the perception
      of complex sounds. 

PMID- 24137018
TI  - Mechanisms of glutamate transport.
AB  - L-Glutamate is the predominant excitatory neurotransmitter in the mammalian
      central nervous system and plays important roles in a wide variety of brain
      functions, but it is also a key player in the pathogenesis of many neurological
      disorders. The control of glutamate concentrations is critical to the normal
      functioning of the central nervous system, and in this review we discuss how
      glutamate transporters regulate glutamate concentrations to maintain dynamic
      signaling mechanisms between neurons. In 2004, the crystal structure of a
      prokaryotic homolog of the mammalian glutamate transporter family of proteins was
      crystallized and its structure determined. This has paved the way for a better
      understanding of the structural basis for glutamate transporter function. In this
      review we provide a broad perspective of this field of research, but focus
      primarily on the more recent studies with a particular emphasis on how our
      understanding of the structure of glutamate transporters has generated new
      insights.

PMID- 24137016
TI  - Physiological roles of aquaporin-4 in brain.
AB  - Aquaporin-4 (AQP4) is one of the most abundant molecules in the brain and is
      particularly prevalent in astrocytic membranes at the blood-brain and brain
      liquor interfaces. While AQP4 has been implicated in a number of
      pathophysiological processes, its role in brain physiology has remained elusive.
      Only recently has evidence accumulated to suggest that AQP4 is involved in such
      diverse functions as regulation of extracellular space volume, potassium
      buffering, cerebrospinal fluid circulation, interstitial fluid resorption, waste
      clearance, neuroinflammation, osmosensation, cell migration, and Ca(2+)
      signaling. AQP4 is also required for normal function of the retina, inner ear,
      and olfactory system. A review will be provided of the physiological roles of
      AQP4 in brain and of the growing list of data that emphasize the polarized nature
      of astrocytes. 

PMID- 24137019
TI  - Small G proteins in the cardiovascular system: physiological and pathological
      aspects.
AB  - Small G proteins exist in eukaryotes from yeast to human and constitute the Ras
      superfamily comprising more than 100 members. This superfamily is structurally
      classified into five families: the Ras, Rho, Rab, Arf, and Ran families that
      control a wide variety of cell and biological functions through highly
      coordinated regulation processes. Increasing evidence has accumulated to identify
      small G proteins and their regulators as key players of the cardiovascular
      physiology that control a large panel of cardiac (heart rhythm, contraction,
      hypertrophy) and vascular functions (angiogenesis, vascular permeability,
      vasoconstriction). Indeed, basal Ras protein activity is required for homeostatic
      functions in physiological conditions, but sustained overactivation of Ras
      proteins or spatiotemporal dysregulation of Ras signaling pathways has
      pathological consequences in the cardiovascular system. The primary object of
      this review is to provide a comprehensive overview of the current progress in our
      understanding of the role of small G proteins and their regulators in
      cardiovascular physiology and pathologies. 

PMID- 24137020
TI  - Systemic iron homeostasis.
AB  - The iron hormone hepcidin and its receptor and cellular iron exporter ferroportin
      control the major fluxes of iron into blood plasma: intestinal iron absorption,
      the delivery of recycled iron from macrophages, and the release of stored iron
      from hepatocytes. Because iron losses are comparatively very small, iron
      absorption and its regulation by hepcidin and ferroportin determine total body
      iron content. Hepcidin is in turn feedback-regulated by plasma iron concentration
      and iron stores, and negatively regulated by the activity of erythrocyte
      precursors, the dominant consumers of iron. Hepcidin and ferroportin also play a
      role in host defense and inflammation, and hepcidin synthesis is induced by
      inflammatory signals including interleukin-6 and activin B. This review
      summarizes and discusses recent progress in molecular characterization of
      systemic iron homeostasis and its disorders, and identifies areas for further
      investigation. 

PMID- 24137021
TI  - Postischemic revascularization: from cellular and molecular mechanisms to
      clinical applications.
AB  - After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of
      molecular, cellular, and extracellular responses that determine the function and
      the remodeling of the ischemic tissue. Hypoxia-related pathways,
      immunoinflammatory balance, circulating or local vascular progenitor cells, as
      well as changes in hemodynamical forces within vascular wall trigger all the
      processes regulating vascular homeostasis, including vasculogenesis,
      angiogenesis, arteriogenesis, and collateral growth, which act in concert to
      establish a functional vascular network in ischemic zones. In patients with
      ischemic diseases, most of the cellular (mainly those involving bone marrow
      derived cells and local stem/progenitor cells) and molecular mechanisms involved
      in the activation of vessel growth and vascular remodeling are markedly impaired
      by the deleterious microenvironment characterized by fibrosis, inflammation,
      hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs.
      Furthermore, cardiovascular risk factors, including diabetes,
      hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious
      macroenvironment that participates to the abrogation of postischemic
      revascularization and tissue regeneration observed in these patient populations.
      Thus stimulation of vessel growth and/or remodeling has emerged as a new
      therapeutic option in patients with ischemic diseases. Many strategies of
      therapeutic revascularization, based on the administration of growth factors or
      stem/progenitor cells from diverse sources, have been proposed and are currently
      tested in patients with peripheral arterial disease or cardiac diseases. This
      review provides an overview from our current knowledge regarding molecular and
      cellular mechanisms involved in postischemic revascularization, as well as
      advances in the clinical application of such strategies of therapeutic
      revascularization. 

PMID- 24137022
TI  - Physiology and pathophysiology of carnosine.
AB  - Carnosine (beta-alanyl-l-histidine) was discovered in 1900 as an abundant non
      protein nitrogen-containing compound of meat. The dipeptide is not only found in
      skeletal muscle, but also in other excitable tissues. Most animals, except
      humans, also possess a methylated variant of carnosine, either anserine or
      ophidine/balenine, collectively called the histidine-containing dipeptides. This
      review aims to decipher the physiological roles of carnosine, based on its
      biochemical properties. The latter include pH-buffering, metal-ion chelation, and
      antioxidant capacity as well as the capacity to protect against formation of
      advanced glycation and lipoxidation end-products. For these reasons, the
      therapeutic potential of carnosine supplementation has been tested in numerous
      diseases in which ischemic or oxidative stress are involved. For several
      pathologies, such as diabetes and its complications, ocular disease, aging, and
      neurological disorders, promising preclinical and clinical results have been
      obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme
      actively degrading carnosine into l-histidine and beta-alanine, is discussed. The
      carnosine system has evolved as a pluripotent solution to a number of homeostatic
      challenges. l-Histidine, and more specifically its imidazole moiety, appears to
      be the prime bioactive component, whereas beta-alanine is mainly regulating the
      synthesis of the dipeptide. This paper summarizes a century of scientific
      exploration on the (patho)physiological role of carnosine and related compounds.
      However, far more experiments in the fields of physiology and related disciplines
      (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a
      full understanding of the function and applications of this intriguing molecule. 

PMID- 24137023
TI  - Cerebrospinal fluid secretion by the choroid plexus.
AB  - The choroid plexus epithelium is a cuboidal cell monolayer, which produces the
      majority of the cerebrospinal fluid. The concerted action of a variety of
      integral membrane proteins mediates the transepithelial movement of solutes and
      water across the epithelium. Secretion by the choroid plexus is characterized by
      an extremely high rate and by the unusual cellular polarization of well-known
      epithelial transport proteins. This review focuses on the specific ion and water
      transport by the choroid plexus cells, and then attempts to integrate the action
      of specific transport proteins to formulate a model of cerebrospinal fluid
      secretion. Significant emphasis is placed on the concept of isotonic fluid
      transport across epithelia, as there is still surprisingly little consensus on
      the basic biophysics of this phenomenon. The role of the choroid plexus in the
      regulation of fluid and electrolyte balance in the central nervous system is
      discussed, and choroid plexus dysfunctions are described in a very diverse set of
      clinical conditions such as aging, Alzheimer's disease, brain edema, neoplasms,
      and hydrocephalus. Although the choroid plexus may only have an indirect
      influence on the pathogenesis of these conditions, the ability to modify
      epithelial function may be an important component of future therapies. 

PMID- 24137024
TI  - Childhood infections, antibiotics, and resistance: what are parents saying now?
AB  - Parental misconceptions and even "demand" for unnecessary antibiotics were
      previously viewed as contributors to overuse of these agents. We conducted focus
      groups to explore the knowledge and attitudes surrounding common infections and
      antibiotic use in the current era of more judicious prescribing. Among diverse
      groups of parents, we found widespread use of home remedies and considerable
      concern regarding antibiotic resistance. Parents generally expressed the desire
      to use antibiotics only when necessary. There was appreciation of inherent error
      in the diagnosis of common infections, with most trust placed in providers with
      whom parents had long-standing relationships. While some parents had experience
      with "watchful waiting" for otitis media, there was little enthusiasm for this
      approach. While there may still be room for further education, it appears that
      parents have become more informed and sophisticated regarding appropriate uses of
      antibiotics. This has likely contributed to the declines seen in their use
      nationally. 

PMID- 24137025
TI  - Are nasopharyngeal cultures useful in diagnosis of acute bacterial sinusitis in
      children?
AB  - The diagnosis of acute bacterial sinusitis can be challenging because symptoms of
      acute sinusitis and an upper respiratory tract infection (URI) overlap. A rapid
      test, if accurate in differentiating sinusitis from URI, could be helpful in the
      diagnostic process. We examined the utility of nasopharyngeal cultures in
      identifying the subgroup of children with a clinical diagnosis of acute sinusitis
      who are least likely to benefit from antimicrobial therapy (those with completely
      normal sinus radiographs). Nasopharyngeal swabs were collected from 204 children
      meeting a priori clinical criteria for acute sinusitis. All children had sinus X
      rays at the time of diagnosis. To determine if negative nasopharyngeal culture
      results could reliably identify the subgroup of children with normal radiographs,
      we calculated negative predictive values and negative likelihood ratios. Absence
      of pathogens in the nasopharynx was not helpful in identifying this low-risk
      subgroup. 

PMID- 24137026
TI  - Obese children in a community YMCA "Fun 2B Fit" program have a reduction in BMI Z
      scores.

PMID- 24137027
TI  - Tracheobronchial foreign body aspiration in children.

PMID- 24137028
TI  - Hepatitis a screening for internationally adopted children from hepatitis A
      endemic countries.
AB  - Screening for hepatitis A virus (HAV) infection is not currently routinely
      recommended in internationally adopted children. International adoptees seen at
      the University of Minnesota International Adoption Clinic from 2006 to 2010 were
      assessed for acute HAV infection (positive HAV immunoglobulin M). Thirty of the
      656 children screened (4.6%) were acutely HAV infected. HAV-infected children
      emigrated from Ethiopia (16), Guatemala (4), China (2), Colombia (2), Haiti (2),
      Philippines (2), Liberia (1), and Nepal (1). Infection was most frequent among
      children younger than 2 years (6.7%). No symptoms distinguished children with
      acute HAV infection from uninfected children. HAV infection caused significant
      social disruption, including separation of children from their ill adoptive
      parents during the initial weeks postarrival, a period important for postadoption
      adjustment and attachment. All international adoptees arriving from countries
      with high or intermediate HAV endemicity should be screened for HAV infection on
      arrival to the United States. 

PMID- 24137029
TI  - How often do providers discuss asthma action plans with children? Analysis of
      transcripts of medical visits.
AB  - OBJECTIVE: To examine how often providers discussed asthma action plans with
      children and their caregivers and child, clinical, and provider characteristics
      that were associated with those discussions. METHOD: This was a cross-sectional
      analysis of audio-recorded visits between 35 general pediatric providers and 260
      children (8-16 years old) with asthma and their caregivers. The visits were
      transcribed into text. The transcripts were coded for discussions about written
      asthma action plans. RESULTS: Providers discussed written asthma action plans
      with 21.0% of children and caregivers. Providers were significantly more likely
      to discuss asthma action plans when the child was enrolled in Medicaid, the visit
      was asthma related, the visit was longer, the provider was not White, or more
      provider education. CONCLUSION: In our sample, providers rarely discussed action
      plans with children and their caregivers. Providers should discuss asthma action
      plans with every child with persistent asthma and their caregivers and revise
      them regularly.

PMID- 24137030
TI  - Seizure and meningoencephalitis in an adolescent.

PMID- 24137031
TI  - Asymmetric crying facies in the 22q11.2 deletion syndrome: implications for
      future screening.
AB  - OBJECTIVE: Asymmetric crying facies (ACF) is congenital hypoplasia of the
      depressor anguli oris muscle characterized by asymmetry of lower lip depression
      during crying. This has an overall incidence of 0.6%. This study determines the
      incidence of ACF in a large population of patients with 22q11.2 deletion.
      PATIENTS AND METHODS: A retrospective review of medical records on patients with
      a confirmed 22q11.2 deletion was undertaken. RESULTS: A total of 836 records were
      reviewed. Of these, 117 (14%) were noted to have ACF on physical examination.
      Within this latter group, palatal anomalies were common (77%), as was congenital
      heart disease (78%); however, these numbers did not differ significantly from
      their known prevalence in the 22q11.2 population. CONCLUSIONS: We report a 14%
      incidence of ACF in patients with a 22q11.2 deletion, significantly higher than
      in the general population. We suggest, therefore, that newborns with ACF be
      referred for further screening for the 22q11.2 deletion syndrome.

PMID- 24137032
TI  - Scurvy mimicking osteomyelitis: case report and review of the literature.

PMID- 24137033
TI  - Parent perspectives on the design of a personal online pediatric immunization
      record.
AB  - OBJECTIVE: To examine desired characteristics of an online immunization record
      for parents from a predominantly Latino, low-income population. METHODS: Four
      focus groups were conducted with parents (n = 29) from an urban, primarily
      Latino, low-income population in New York. The data were collected and analyzed
      during winter 2008-2009. RESULTS: Participants expressed interest in using an
      online immunization record that has the ability to show a child's immunization
      status and to access consumer health information related to vaccinations.
      Participants suggested that the online record be translated into multiple
      languages and provide user-friendly interfaces. Participants were enthusiastic
      about the benefits offered by the online immunization record, highlighting having
      an electronic copy of their child's immunization record available. Concerns over
      disclosing personal information were raised, and safeguards to protect
      confidentiality were requested. CONCLUSIONS: If concerns about privacy are
      adequately addressed, parents of low-income, urban children are likely to use and
      benefit from an online immunization record.

PMID- 24137034
TI  - Pediatric nutrition: parenting impacts beyond financial resources.

PMID- 24137035
TI  - Rare-earth magnet ingestion-related injuries among children, 2000-2012.
AB  - This study describes the epidemiology of rare-earth magnet ingestion by children
      by retrospectively analyzing 72 cases of magnet ingestion collected from
      Saferproducts.gov and the US Consumer Product Safety Commission from 2000 through
      2012. The mean child age was 6.4 years. Patients ingested between 1 and 40
      magnets, most often 1 to 4 magnets. Unique circumstances of ingestion included
      faux piercing (19.4%) and mistaking magnets for candy (6.9%). Surgery was
      required in 69.7% of cases where treatment was reported. Fifty-three patients
      were hospitalized (73.6%), and the length of hospital stay was reported in 58.5%
      of those cases, ranging from 1 to 54 days. Approximately half (50.7%) of the
      magnets causing injury were products intended for use by adults. Study findings
      demonstrate that pediatric ingestion of rare-earth magnets can cause serious
      gastrointestinal injury. Establishing a performance standard that limits the
      attraction force of these magnets offers the best prevention solution to this
      important pediatric public health problem. 

PMID- 24137036
TI  - An Inpatient Child Passenger Safety program.
AB  - Background. Our institution implemented an Inpatient Child Passenger Safety (CPS)
      program for hospitalized children to improve knowledge and compliance with the
      Massachusetts CPS law, requiring children less than 8 years old or 57 inches tall
      to be secured in a car seat when in a motor vehicle. Methods. After the Inpatient
      CPS Program was piloted on 3 units in 2009, the program was expanded to all
      inpatient units in 2010. A computerized nursing assessment tool identifies
      children in need of a CPS consult for education and/or car seat. Results. With
      the expanded Inpatient CPS Program, 3650 children have been assessed, 598
      consults initiated, and 325 families have received CPS education. Car seats were
      distributed to 419 children; specialty car seats were loaned to 134 families.
      Conclusions. With a multidisciplinary approach, we implemented an Inpatient CPS
      Program for hospitalized children providing CPS education and car seats to
      families in need. 

PMID- 24137037
TI  - Intussusception in children presenting to the emergency department.
AB  - A retrospective chart review of children diagnosed with intussusceptions from
      March 2005 to March 2007 was conducted at a tertiary care pediatric hospital.
      There were 152 children with 170 episodes of intussusceptions during the study
      period. Around one third (30%) of children diagnosed with intussusceptions had a
      concurrent infection. There were 114 large bowel intussusceptions, with a mean
      age of 27 months (SD = 25) and a success rate of 91% for air enema reductions.
      Bowel resection was performed in 8.8% of children with large bowel
      intussusceptions. Small bowel intussusceptions (n = 38) were associated with
      gastrostomy tubes in 42% (n = 16) of patients, and 81% needed tube shortening.
      The varying age range of many children diagnosed with intussusceptions and the
      high incidence of intercurrent illnesses and fever in our study alert health
      professionals to suspect intussusceptions in children presenting with abdominal
      pain or crying. 

PMID- 24137038
TI  - An orthodontic retainer preventing remission in celiac disease.
AB  - Celiac disease is a gluten enteropathy that is treated with dietary elimination
      of gluten. Exposure to nondietary sources of gluten, which are used in the
      manufacture of products such as plastics, dental equipment, and cosmetics, can
      also trigger or exacerbate disease. We report the case of a 9-year-old child who
      presented with nonspecific abdominal discomfort with abnormal serology for celiac
      disease. She underwent duodenal biopsies that revealed Marsh 3B histopathology.
      Despite strict dietary elimination of gluten, she continued to be symptomatic and
      demonstrate positive serum markers for active disease. It was then discovered
      that the child was exposed to gluten from her orthodontic retainer that contained
      a plasticized methacrylate polymer. Gluten is a common additive in plastics. She
      discontinued its use and demonstrated symptom resolution and complete
      normalization of serology. All possible sources of gluten, including nondietary,
      must be considered when managing a child with celiac disease. 

PMID- 24137039
TI  - Ventilator caregiver education through the use of high-fidelity pediatric
      simulators: a pilot study.
AB  - Introduction. Home ventilator programs (HVP) have been developed to train parents
      of critically ill children. Simulators are used in health care, but not often for
      parents. We added simulation to our HVP and assessed parents' response. Methods.
      In July 2008, the HVP at Children's of Alabama added simulation to parent
      training. Debriefing was provided after the training session to reinforce correct
      skills and critical thinking. Follow-up surveys were completed after training.
      Results. Fifteen families participated. All parents were confident in changing
      tracheostomies, knowing signs of breathing difficulties, and responding to
      alarms. 71% strongly agree that simulation resulted in feeling better prepared to
      care for their child. 86% felt simulation improved their confidence in taking
      care of their child. Conclusion. Simulators provide a crucial transition between
      learned skills and application. This novel use of simulation-based education
      improves parents' confidence in emergencies and may lead to shortened training
      resulting in cost savings. 

PMID- 24137040
TI  - Safe sleep practices and sudden infant death syndrome risk reduction: NICU and
      well-baby nursery graduates.
AB  - Our primary objective was to compare parents of infants cared for in newborn
      intensive care units (NICUs) and infants cared for in well-baby ("general")
      nurseries with regard to knowledge and practice of safe sleep practices/sudden
      infant death syndrome risk reduction measures and guidelines. Our secondary
      objective was to obtain qualitative data regarding reasons for noncompliance in
      both populations. Sixty participants (30 from each population) completed our
      survey measuring safe sleep knowledge and practice. Parents of NICU infants
      reported using 2 safe sleep practices-(a) always placing baby in crib to sleep
      and (b) always placing baby on back to sleep-significantly more frequently than
      parents of well infants. Additional findings and implications for future studies
      are discussed. 

PMID- 24137041
TI  - A phase I/II seamless dose escalation/expansion with adaptive randomization
      scheme (SEARS).
AB  - BACKGROUND: Standard drug development conducts phase I dose finding and phase II
      dose expansion sequentially and separately. Information between the two phases is
      rarely shared. Administratively, such a sequential process is time-consuming and
      burdensome. PURPOSE: We propose seamless dose escalation/expansion with adaptive
      randomization scheme (SEARS), a seamless design that combines phase I dose
      escalation based on toxicity with phase II dose expansion and dose comparison
      based on efficacy. SEARS allows extension from phase I to phase II under one
      design with no gap in between and employs a dynamic and parallel procedure
      involving simultaneous dose escalation, dose graduation, and adaptive
      randomization. METHODS: SEARS integrates three components into a seamless scheme.
      Specifically, in phase I, SEARS applies the modified toxicity probability
      interval (mTPI) method to monitor dose escalation based on toxicity outcome.
      Doses that show promising efficacy and safety are immediately graduated from
      phase I and placed to a phase II stage in which patients are adaptively
      randomized based on efficacy outcome. Phase I dose escalation, dose graduation,
      and phase II adaptive randomization proceed simultaneously throughout the entire
      trial. RESULTS: Examples are given comparing SEARS with two other designs, in
      which superior performance of SEARS is demonstrated. An important and promising
      finding is that SEARS reduces sample sizes without losing power. R program and
      demo slides of SEARS can be obtained at
      http://health.bsd.uchicago.edu/yji/soft.html LIMITATION: We assume that the
      binary efficacy and toxicity response can be measured in the same time frame.
      This is often achievable with surrogate efficacy markers in practice.

PMID- 24137042
TI  - Development of an experimental model for assessing the effects of cigarette smoke
      and virus infections on inflammatory responses to bacterial antigens.
AB  - Interactions among major risk factors associated with bacterial infections were
      assessed in a model system using surrogates for virus infection; IFN-g, and
      exposure to cigarette smoke; cigarette smoke extract (CSE), nicotine and
      cotinine. Cytokine responses elicited by LPS from THP-1 cells in the presence of
      these components, or combinations of components, were assessed by multiplex bead
      assay, i.e. IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and IFN-gamma. IFN-gamma
      priming significantly increased pro-inflammatory cytokines induced by LPS. CSE
      suppressed production of pro-inflammatory cytokines IL-1beta, TNF-alpha and IFN
      gamma, but enhanced production of IL-8. Nicotine and cotinine suppressed all
      cytokine responses. In combination, IFN-gamma masked the inhibitory effects of
      CSE. In relation to the objectives of the study, we concluded that (a) IFN-gamma
      at biologically relevant concentrations significantly enhanced pro-inflammatory
      responses; (b) CSE, nicotine and cotinine dysregulated the inflammatory response
      and that the effects of CSE were different from those of the individual
      components, nicotine and cotinine; (c) when both IFN-gamma and CSE were present,
      IFN-gamma masked the effect of CSE. There is a need for clinical investigations
      on the increase in IL-8 responses in relation to exposure to cigarette smoke and
      increased pro-inflammatory responses in relation to recent viral infection. 

PMID- 24137043
TI  - THE EAST AFRICAN MEDICAL JOURNAL: ITS HISTORY AND CONTRIBUTION TO REGIONAL
      MALARIA RESEARCH DURING THE LAST 75 YEARS.
AB  - Since its inception seventy five years ago, the East African Medical Journal has
      provided an uninterrupted forum through which medical practitioners and
      scientists could publish their research. Although the EAMJ was initially prepared
      for an audience of colonial medical officers, by the 1930s the journal expanded
      to include subscription and submissions from Northern Rhodesia (now Zimbabwe) and
      West Africa. Our review begins with a history of the journal's production,
      exploring the shifts in editorial composition. We then focus more directly on a
      discussion of papers and editorials on malaria, a disease that continues to
      challenge the region of East Africa. Our review highlights the importance of the
      journal's commitment to publications on this major health problem within the East
      African environment. Of particular interest, our review shows that many of
      today's concerns, debates and recommendations for control or treatment of malaria
      in East Africa were discussed and debated in earlier issues of the EAMJ. Medical
      policy for the region with regard to malaria will benefit from revisiting
      previous volumes of the EAMJ. These contributions will ensure the journal a
      significant place in the world of research publications for the coming seventy
      five years.

PMID- 24137044
TI  - Flight calls signal group and individual identity but not kinship in a
      cooperatively breeding bird.
AB  - In many complex societies, intricate communication and recognition systems may
      evolve to help support both direct and indirect benefits of group membership. In
      cooperatively breeding species where groups typically comprise relatives, both
      learned and innate vocal signals may serve as reliable cues for kin recognition.
      Here, we investigated vocal communication in the plural cooperatively breeding
      superb starling, Lamprotornis superbus, where flight calls-short, stereotyped
      vocalizations used when approaching conspecifics-may communicate kin
      relationships, group membership, and/or individual identity. We found that flight
      calls were most similar within individual repertoires but were also more similar
      within groups than within the larger population. Although starlings responded
      differently to playback of calls from their own versus other neighboring and
      distant social groups, call similarity was uncorrelated with genetic relatedness.
      Additionally, immigrant females showed similar patterns to birds born in the
      study population. Together, these results suggest that flight calls are learned
      signals that reflect social association but may also carry a signal of
      individuality. Flight calls, therefore, provide a reliable recognition mechanism
      for groups and may also be used to recognize individuals. In complex societies
      comprising related and unrelated individuals, signaling individuality and group
      association, rather than kinship, may be a route to cooperation.

PMID- 24137045
TI  - Rates of agonism among female primates: a cross-taxon perspective.
AB  - Agonism is common in group-living animals, shaping dominance relationships and
      ultimately impacting individual fitness. Rates of agonism vary considerably among
      taxa, however, and explaining this variation has been central in ecological
      models of female social relationships in primates. Early iterations of these
      models posited a link to diet, with more frequent agonism predicted in
      frugivorous species due to the presumed greater contestability of fruits relative
      to other food types. Although some more recent studies have suggested that
      dietary categories may be poor predictors of contest competition among primates,
      to date there have been no broad, cross-taxa comparisons of rates of female
      female agonism in relation to diet. This study tests whether dietary variables do
      indeed predict rates of female agonism and further investigates the role of group
      size (i.e., number of competitors) and substrate use (i.e., degree of
      arboreality) on the frequency of agonism. Data from 44 wild, unprovisioned
      groups, including 3 strepsirhine species, 3 platyrrhines, 5 colobines, 10
      cercopithecines, and 2 hominoids were analyzed using phylogenetically controlled
      and uncontrolled methods. Results indicate that diet does not predict agonistic
      rates, with trends actually being in the opposite direction than predicted for
      all taxa except cercopithecines. In contrast, agonistic rates are positively
      associated with group size and possibly degree of terrestriality. Competitor
      density and perhaps the risk of fighting, thus, appear more important than
      general diet in predicting agonism among female primates. We discuss the
      implications of these results for socio-ecological hypotheses.

PMID- 24137046
TI  - The role of beginner's luck in learning to prefer risky patches by socially
      foraging house sparrows.
AB  - Although there has been extensive research on the evolution of individual
      decision making under risk (when facing variable outcomes), little is known on
      how the evolution of such decision-making mechanisms has been shaped by social
      learning and exploitation. We presented socially foraging house sparrows with a
      choice between scattered feeding wells in which millet seeds were hidden under 2
      types of colored sand: green sand offering ~80 seeds with a probability of 0.1
      (high risk-high reward) and yellow sand offering 1 seed with certainty (low risk
      low reward). Although the expected benefit of choosing variable wells was 8 times
      higher than that of choosing constant wells, only some sparrows developed a
      preference for variable wells, whereas others developed a significant preference
      for constant wells. We found that this dichotomy could be explained by stochastic
      individual differences in sampling success during foraging, rather than by social
      foraging strategies (active searching vs. joining others). Moreover, preference
      for variable or constant wells was related to the sparrows' success during
      searching, rather than during joining others or when picking exposed seeds (i.e.,
      they learn when actively searching in the sand). Finally, although for many
      sparrows learning resulted in an apparently maladaptive risk aversion, group
      living still allowed them to enjoy profitable variable wells by occasionally
      joining variable-preferring sparrows.

PMID- 24137048
TI  - Analysis of new functional profiles of protein isoforms yielded by ds exonization
      in rice.
AB  - Insertion of transposable elements (TEs) into introns can lead to their
      activation as alternatively spliced cassette exons, an event called exonization.
      Exonization can enrich the complexity of transcriptomes and proteomes.
      Previously, we performed a genome-wide computational analysis of Ds exonization
      events in the monocot Oryza sativa (rice). The insertion patterns of Ds increased
      the number of transcripts and subsequent protein isoforms, which were determined
      as interior and C-terminal variants. In this study, these variants were scanned
      with the PROSITE database in order to identify new functional profiles (domains)
      that were referred to their reference proteins. The new profiles of the variants
      were expected to be beneficial for a selective advantage and more than 70%
      variants achieved this. The new functional profiles could be contributed by an
      exon-intron junction, an intron alone, an intron-TE junction, or a TE alone. A Ds
      inserted intron may yield 167 new profiles on average, while some cases can yield
      thousands of new profiles, of which C-terminal variants were in major.
      Additionally, more than 90% of the TE-inserted genes were found to gain novel
      functional profiles in each intron via exonization. Therefore, new functional
      profiles yielded by the exonization may occur in many local regions of the
      reference protein. 

PMID- 24137047
TI  - Identification, nomenclature, and evolutionary relationships of mitogen-activated
      protein kinase (MAPK) genes in soybean.
AB  - Mitogen-activated protein kinase (MAPK) genes in eukaryotes regulate various
      developmental and physiological processes including those associated with biotic
      and abiotic stresses. Although MAPKs in some plant species including Arabidopsis
      have been identified, they are yet to be identified in soybean. Major objectives
      of this study were to identify GmMAPKs, assess their evolutionary relationships,
      and analyze their functional divergence. We identified a total of 38 MAPKs,
      eleven MAPKKs, and 150 MAPKKKs in soybean. Within the GmMAPK family, we also
      identified a new clade of six genes: four genes with TEY and two genes with TQY
      motifs requiring further investigation into possible legume-specific functions.
      The results indicated the expansion of the GmMAPK families attributable to the
      ancestral polyploidy events followed by chromosomal rearrangements. The GmMAPK
      and GmMAPKKK families were substantially larger than those in other plant
      species. The duplicated GmMAPK members presented complex evolutionary
      relationships and functional divergence when compared to their counterparts in
      Arabidopsis. We also highlighted existing nomenclatural issues, stressing the
      need for nomenclatural consistency. GmMAPK identification is vital to soybean
      crop improvement, and novel insights into the evolutionary relationships will
      enhance our understanding about plant genome evolution. 

PMID- 24137049
TI  - Development and Validation of RP-LC Method for the Determination of
      Cinnarizine/Piracetam and Cinnarizine/Heptaminol Acefyllinate in Presence of
      Cinnarizine Reported Degradation Products.
AB  - Specific stability indicating reverse-phase liquid chromatography (RP-LC) assay
      method (SIAM) was developed for the determination of cinnarizine (Cinn)/piracetam
      (Pira) and cinnarizine (Cinn)/heptaminol acefyllinate (Hept) in the presence of
      the reported degradation products of Cinn. A C18 column and gradient mobile phase
      was applied for good resolution of all peaks. The detection was achieved at 210
      nm and 254 nm for Cinn/Pira and Cinn/Hept, respectively. The responses were
      linear over concentration ranges of 20-200, 20-1000 and 25-1000 MUgmL(-1) for
      Cinn, Pira, and Hept respectively. The proposed method was validated for
      linearity, accuracy, repeatability, intermediate precision, and robustness via
      statistical analysis of the data. The method was shown to be precise, accurate,
      reproducible, sensitive, and selective for the analysis of Cinn/Pira and
      Cinn/Hept in laboratory prepared mixtures and in pharmaceutical formulations. 

PMID- 24137050
TI  - Microscopic colitis and reproductive factors related to exposure to estrogens and
      progesterone.
AB  - Microscopic colitis (MC) often debuts around or after menopause and is divided
      into lymphocytic- and collagenous colitis. The aim of this study was to examine
      whether factors influencing sex hormone levels differed between subgroups of MC
      as well as between patients and controls. A self-administered questionnaire about
      parity was completed which included questions surrounding age at first
      childbirth, menarche and menopause, the use of oral contraceptives, and hormonal
      replacement therapy. Patients with lymphocytic colitis had children less often
      compared to those with collagenous colitis (OR = 0.20, 95% CI = 0.05-0.86),
      however no differences were observed between patients with persistent or
      transient disease. Patients were less often older than 15 years of age at
      menarche (OR = 0.48, 95% CI = 0.26-0.91) and were younger at menopause (OR =
      0.30, 95% CI = 0.16-0.56) compared with controls. Thus, no obvious association
      between factors influencing sex hormone levels and presence of MC could be found.

PMID- 24137051
TI  - Microbial carriage of cockroaches at a tertiary care hospital in ghana.
AB  - Cockroaches are common in the environment of many hospitals in Ghana; however,
      little is known about their public health risks. To evaluate potential risks, we
      investigated the external and internal microbial flora of 61 cockroaches from a
      tertiary hospital in Ghana and evaluated the antibiotic resistance profiles of
      the common bacterial species. Standard methods were used in all the
      microbiological investigations and antibiotic susceptibility testing. A rotavirus
      carriage rate of 19.7% was observed among the cockroaches. Four types of
      intestinal parasites were carried externally by the cockroaches, and the most
      prevalent was Hookworm (4.9%). Eight nosocomial bacteria were isolated from the
      cockroaches, and the most prevalent was Klebsiella pneumoniae, which occurred
      internally in 29.5% of the cockroaches and 26.2% externally. Multiple drug
      resistance among common bacteria isolated from the cockroaches ranged from 13.8%
      (Escherichia coli) to 41.1% (Klebsiella pneumoniae). Cockroaches constitute an
      important reservoir for pathogenic microorganisms, and may be important vectors
      of multiple resistant nosocomial pathogens in the studied hospital. 

PMID- 24137052
TI  - Comparing the Performance of Hybrid Capture II and Polymerase Chain Reaction
      (PCR) for the Identification of Cervical Dysplasia in the Screening and
      Diagnostic Settings.
AB  - OBJECTIVE: Both PCR and Hybrid Capture II (HCII) have been used for identifying
      cervical dysplasia; however, comparisons on the performance between these two
      tests show inconsistent results. We evaluated the performance of HCII and PCR
      MY09/11 in both screening and diagnostic populations in sub-sample of 1,675 non
      pregnant women from a cohort in three clinical centers in the United States and
      Canada. METHODS: Sensitivity, specificity, positive predictive value, negative
      predictive value, and concordance between the two tests were calculated. RESULTS:
      Specificity of HCII in detecting low-grade squamous intraepithelial lesion (LSIL)
      was higher in the screening group (88.7%; 95% CI: 86.2%-90.8%) compared to the
      diagnostic group (46.3%; 95% CI: 42.1%-50.6%); however, specificity of PCR was
      low in both the screening (32.8%; 95% CI: 29.6%-36.2%) and diagnostic (14.4%; 95%
      CI: 11.6%-17.6%) groups. There was comparable sensitivity by both tests in both
      groups to detect high-grade squamous intraepithelial lesion (HSIL); however, HCII
      was more specific (89.1%; 95% CI: 86.8%-91.0%; 66.2%; 95% CI: 62.0%-70.1%) than
      PCR (33.3%; 95% CI: 30.2%-36.5%; 17.9%; 95% CI: 14.8%-21.6%) in the screening and
      diagnostic groups, respectively. Overall agreement for HPV positivity was
      approximately 50% between HCII and PCR MY09/11; with more positive results coming
      from the PCR MY09/11. CONCLUSION: In the current study, PCR MY09/11 was more
      sensitive but less specific than HCII in detecting LSIL, and HCII was more
      sensitive and specific in detecting HSIL than PCR in both screening and
      diagnostic groups.

PMID- 24137053
TI  - Primary monophasic synovial sarcoma of the kidney: a case report and review of
      literature.
AB  - Primary synovial sarcoma (SS) of the kidney is a rare neoplasm and its presenting
      features are similar to other common renal tumors, making early diagnosis
      difficult. To date, few cases have been reported in the literature. Primary renal
      SSs can exist in either a monophasic or a biphasic pattern, the former being more
      common and tending to have a better prognosis than the biphasic variant. Herein
      we describe a case of primary renal SS that was diagnosed based on histopathology
      and immunohistochemistry after radical nephrectomy. Fusion gene product analysis
      was also done by FISH and RT-PCR. Patient follow-up and literature review are
      presented, focused on systemic therapy. We highlight that these tumors should be
      correctly diagnosed as clinical results and specific treatment are distinct from
      primary epithelial renal cell carcinoma. Adjuvant chemotherapy should be tailored
      for each patient in the management of disease, although its role still remains
      unclear. 

PMID- 24137054
TI  - Can the power balance((r)) bracelet improve balance, flexibility, strength, and
      power?

PMID- 24137055
TI  - Response to the Study of Gomez-Lopez et al. "Perceived Barriers by University
      Students in the Practice of Physical Activities. J sport Sci & MED 9, 374-38,
      2010".

PMID- 24137056
TI  - Reliability and Accuracy of 10 Hz GPS Devices for Short-Distance Exercise.

PMID- 24137057
TI  - Laboratory Testing and Field Performance in BMX Riders.

PMID- 24137058
TI  - Time Motion Analysis of Supercross BMX Racing.

PMID- 24137059
TI  - On the Evaluation of Postural Stability after ACL Recostruction.

PMID- 24137060
TI  - Treadmill Exercise Improves Impaired Spatial Memory Function in Partial androgen
      Deficiency Rat Model.

PMID- 24137061
TI  - Does the Shake Weight((r)) live up to its hype?

PMID- 24137062
TI  - Fear of Re-Injury does not Differ Between those with and without Chronic Ankle
      Instability.

PMID- 24137063
TI  - The Effect of Tele-Monitoring on Exercise Training Adherence, Functional
      Capacity, Quality of Life and Glycemic Control in Patients With Type II Diabetes.
AB  - ABSTRACT: We used tele-monitoring to attempt to improve exercise adherence
      (number of hours of exercise completed), peak VO2, HbA1c% and quality of life in
      an unsupervised, home based exercise program in people with type II diabetes, a
      cost analysis was also conducted. Thirty-nine patients with type II diabetes were
      randomized to tele-monitoring (TELE) or control (CON) groups. All patients were
      asked to complete 6 months exercise training and complete an exercise activity
      diary. The TELE group was instructed to record their exercise heart rates using a
      monitor and received weekly telephone calls from an exercise physiologist. Six
      TELE patients and seven CON patients did not complete the 6 month testing. TELE
      patients completed a mean weekly volume of 138 minutes, moderate intensity
      exercise, while CON patients completed 58 minutes weekly (p < 0.02). Neither
      group achieved the American Heart Association statement guideline for weekly
      exercise volume of 150 minutes. TELE patients improved peak VO2 (5.5 %), but
      neither group improved HbA1c% or quality of life. The CON group showed a 4.9%
      reduction in peak VO2. While tele-monitored patients completed more hours of
      exercise and demonstrated improved peak VO2 compared to controls, the exercise
      volume completed was insufficient to improve glycemic control. There is the
      potential via tele-monitoring to enable people with diabetes to meet exercise
      training guidelines. KEY POINTS: Weekly telephone calls from a health
      professional providing encouragement, increases the amount of exercise completed
      by people with diabetesWeekly telephone calls will result in improved fitnessAt
      least 150 minutes weekly exercise is required to improve diabetes controlThe cost
      of home exercise with telephone monitoring is cheaper (and more convenient for
      the patient) than delivering an exercise program at the hospitalLonger term
      research is needed to examine whether telephone supervised exercise will prevent
      serious events such as heart attack, strokes and death.

PMID- 24137064
TI  - Effects of Motorized vs Non-Motorized Treadmill Training on Hamstring/Quadriceps
      Strength Ratios.
AB  - Previous literature suggests that muscular involvement and biomechanical changes
      elicit different responses between overground and treadmill training. The
      objective of this study was to examine the effects of training on two different
      treadmill designs on the conventional (CR; concentric only) and functional (FR;
      eccentric to concentric) hamstring and quadriceps strength ratios. Fifteen men
      and sixteen women were randomly divided into three groups: motorized (MT), non
      motorized (NMT) or control (C). Subjects completed pre and post-test isokinetic
      concentric and eccentric quadriceps and hamstring testing of both legs. Subjects
      completed 4 weeks of training on their respective treadmills with mileage
      increasing 1/2 mile each week, beginning with 2 miles. The C group did not
      participate in any training. The CR revealed a significant two way interaction of
      group x time with MT increasing (pre: 0.80 +/- 0.09 to post: 0.84 +/- 0.09), NMT
      decreasing (pre: 0.76 +/- 0.13 to post: 0.74 +/- 0.10), and C showing no change
      (pre: 0.79 +/- 0.10 to post: 0.79 +/- 0.09. The FR revealed a significant two way
      interaction of speed x sex with the FR increasing as speeds increased for men (60
      degrees.s(-1): 1.04 +/- 0.11; 180 degrees.s(-1): 1.66 +/- 0.27; 300 degrees.s(
      1): 2.36 +/- 0.45) and women (60 degrees.s(-1): 1.05 +/- 0.16; 180 degrees.s(-1):
      1.90 +/- 0.26; 300 degrees.s(-1): 2.75 +/- 0.47) but women increased greater
      relative to men. Training mode elicited a specific change in concentric hamstring
      and quadriceps strength resulting in specific changes to the CR; however, neither
      training mode had an effect on eccentric hamstrings nor the FR. Special attention
      should be given to the mode of endurance training when the goal is to alter the
      hamstring/quadriceps CR. KEY POINTS: Specificity of treadmill training had
      different effects on concentric strength.Specificity of treadmill training had
      little or no effect on eccentric strength.Conventional and functional strength
      ratios may give different results based on training mode.Four weeks is long
      enough for strength results to be apparent in untrained people.

PMID- 24137065
TI  - Kinematic changes during a marathon for fast and slow runners.
AB  - The purpose of this study was to describe kinematic changes that occur during an
      actual marathon. We hypothesized that (1) certain running kinematic measures
      would change between kilometres 8 and 40 (miles 5 and 25) of a marathon and (2)
      fast runners would demonstrate smaller changes than slow runners. Subjects (n =
      179) were selected according to finish time (Range = 2:20:47 to 5:30:10). Two
      high-speed cameras were used to measure sagittal-plane kinematics at kilometres 8
      and 40 of the marathon. The dependent variables were stride length, contact time,
      peak knee flexion during support and swing, and peak hip flexion and extension
      during swing. Two-tailed paired t-tests were used to compare dependent variables
      between kilometres 8 and 40 for all subjects, and regression analyses were used
      to determine whether faster runners exhibited smaller changes (between miles 5
      and 25) than slower runners. For all runners, every dependent variable changed
      significantly between kilometres 8 and 40 (p < 0.001). Stride length increased
      1.3%, contact time increased 13.1%, peak knee flexion during support decreased
      3.2%, and peak hip extension, knee flexion, and hip flexion during swing
      decreased 27.9%, increased 4.3%, and increased 7.4%, respectively (p < 0.001).
      Among these significant changes, all runners generally changed the same from
      kilometres 8 and 40 except that fast runners decreased peak knee flexion during
      support less than the slow runners (p < 0.002). We believe that these changes,
      for all runners (fast and slow), were due to fatigue. The fact that fast runners
      maintained knee flexion during support more consistently might be due to their
      condition on the race day. Strengthening of knee extensor muscles may facilitate
      increased knee flexion during support throughout a marathon. KEY POINTS: Runners
      changed kinematics significantly from kilometres 8 to 40 (increased stride
      length, contact time, peak hip flexion during swing, and peak knee flexion during
      swing, and decreased running speed, stride frequency, peak knee flexion during
      support and peak hip extension during swing).Fast runners demonstrated more peak
      knee flexion during support throughout a marathon.Runners generally changed
      kinematics similarly (between kilometres 8 and 40) except that fast runners
      exhibited a more consistent peak knee flexion during support than slow
      runners.Resistance training that would increase both muscular strength and
      endurance of knee extensors may increase peak knee flexion during support and
      help maintain it similar to the fast runners throughout a marathon.

PMID- 24137066
TI  - Different circulating brain-derived neurotrophic factor responses to acute
      exercise between physically active and sedentary subjects.
AB  - Although circulating brain-derived neurotrophic factor (BDNF) level is affected
      by both acute and chronic physical activity, the interaction of acute and chronic
      physical activity was still unclear. In this study, we compared the serum and
      plasma BDNF responses to maximal and submaximal acute exercises between
      physically active and sedentary subjects. Eight active and 8 sedentary female
      subjects participated in the present study. Both groups performed 3 exercise
      tests with different intensities, i.e. 100% (maximal), 60% (moderate) and 40%
      (low) of their peak oxygen uptake. In each exercise test, blood samples were
      taken at the baseline and immediately, 30 and 60 min after the test. The serum
      BDNF concentration was found to significantly increase immediately after maximal
      and moderate exercise tests in both groups. In maximal exercise test, the pattern
      of change in the serum BDNF concentration was different between the groups. While
      the serum BDNF level for the sedentary group returned to the baseline level
      during the recovery phase, the BDNF levels for the active group decreased below
      the baseline level after the maximal exercise test. No group differences were
      observed in the pattern of plasma BDNF change for all exercise tests. These
      findings suggest that regular exercise facilitates the utilization of circulating
      BDNF during and/or after acute exercise with maximal intensity. KEY POINTS: In
      maximal exercise test, the pattern of change in the serum BDNF concentration was
      different between the groups.While the serum BDNF level for the sedentary group
      returned to the baseline level during the recovery phase, the BDNF levels for the
      active group decreased below the baseline level after the maximal exercise
      test.No group differences were observed in the pattern of serum BDNF change for
      moderate or low exercise tests.No group differences were observed in the pattern
      of plasma BDNF change for all exercise tests.

PMID- 24137067
TI  - Reliability and validity of a wireless microelectromechanicals based system
      (keimoveTM) for measuring vertical jumping performance.
AB  - The aim of this study was to determine the validity and reliability of a
      microelectromechanicals (MEMs) based system (KeimoveTM) in measuring flight time
      and takeoff velocity during a counter-movement jump (CMJ). As criterion
      reference, data of a high- speed camera (HSC) and a force-platform (FP)
      synchronized with a linear position transducer (LPT) was used. Thirty
      professional soccer players completely familiarized with the CMJ technique
      performed three CMJs. The second and third trials were used for further analysis.
      The KeimoveTM system, the HSC and the FP synchronized with the LPT (FP+LPT)
      simultaneously measured the CMJ performance. During each repetition, the
      KeimoveTM system registered flight time and velocity at takeoff. At the same time
      and as criterion reference, both the HSC and the FP recorded the flight time
      while the LPT+FP registered the velocity at takeoff. Pearson correlation
      coefficients for the flight time were high (r = 0.99; p < 0.001) when KeimoveTM
      system was compared with the HSC or the FP+LPT, respectively. For the velocity at
      takeoff variable, the Pearson r between the KeimoveTM system and the FP+LPT was
      lower although significant at the 0.05 level. No significant differences in mean
      values were observed for flight times and velocity at takeoff between the three
      devices. Intraclass correlations and coefficients of variation between trials
      were similar and ranged between 0.92-0.97 and 2.1-7.4, respectively. In
      conclusion, the KeimoveTM system represents a valid and reliable instrument to
      measure velocity at takeoff and flight time during CMJ testing. Thus, this MEMs
      based system will offer a portable, cost-effective tool for the assessment CMJ
      performance. KEY POINTS: The KeimoveTM system is composed of specific software
      and a wireless MEMs-based device designed to be attached at the lumbar region of
      the athlete.The KeimoveTM system is a mechanically valid and reliable instrument
      in measuring flight time and velocity at takeoff during CMJ.The validity of the
      KeimoveTM system was determined by comparing its mean flight time and velocity at
      takeoff with data obtained simultaneously with both a high-speed camera and a
      force platform synchronized with a linear position transducer.

PMID- 24137068
TI  - The relationship between teaching styles and motivation to teach among physical
      education teachers.
AB  - This study aims to investigate how teachers' motivation to teach is related to
      different teaching styles. A hundred and seventy six physical education teachers
      from five European countries participated in the study. Teachers' motivation was
      measured using an instrument developed by Roth et al., 2007 based on the Self
      Determination Theory (Deci and Ryan, 1985) which was tested for suitability for
      use with physical education teachers. The use of teaching styles was assessed
      through teachers' self-reported data according to the description of teaching
      styles presented by Curtner-Smith et al., 2001. The revised confirmatory factor
      model of the teachers' motivation instrument, with three factors, met the
      criteria for satisfactory fit indices. The results showed that teachers were more
      intrinsically motivated to teach than externally. Cross-cultural comparison
      indicated that the Spanish teachers were more intrinsically motivated whilst
      Lithuanian teachers were more externally motivated than teachers from the other
      four countries. Teachers from all five countries reported a more frequent use of
      reproductive styles than productive styles. The results of the present study
      confirmed the hypotheses that teachers' autonomous motivation is related to the
      student-centered or productive teaching styles whilst non-autonomously motivated
      teachers adopt more teacher-centered or reproductive teaching styles. Intrinsic
      and introjected motivation was significantly higher among teachers who more
      frequently employed productive teaching styles than teachers who used them less
      frequently. Intrinsically motivated teachers using more productive teaching
      styles can contribute more to the promotion physical activity among students. KEY
      POINTS: PE teachers were more intrinsically motivated to teach than
      externally.Spanish PE teachers were more intrinsically motivated, whereas
      Lithuanian PE teachers were more externally motivated.Teachers from all five
      countries reported a more frequent use of reproductive styles than productive
      styles.Teachers' autonomous motivation is related to student-centered teaching
      styles and not autonomously motivated teachers adopt more teacher-centered
      teaching styles.Intrinsic and introjected motivations were significantly higher
      among PE teachers using frequently productive teaching styles.

PMID- 24137069
TI  - High prevalence of patellar and achilles tendinopathies in futsal athletese.

PMID- 24137070
TI  - Validation of the oxycon mobile metabolic system in healthy subjects.

PMID- 24137071
TI  - Cervical spine anomalies: a contraindication to sports?

PMID- 24137072
TI  - Zumba((r)): is the "fitness-party" a good workout?

PMID- 24137073
TI  - Exercise intensity of recreational sport: impacts of sex and fitness.

PMID- 24137074
TI  - The facemask produces higher peak minute ventilation and respiratory rate
      measurements compared to the mouthpiece.

PMID- 24137075
TI  - Do toning pants help to give you a better workout?

PMID- 24137076
TI  - Turn It On!: The Relative Exercise Intensity and Caloric Expenditure of
      QiDanceTM.

PMID- 24137077
TI  - Repeated bout effect and cross-transfer: evidence of dominance influence.

PMID- 24137078
TI  - Does man age faster at the everest peak? A hypothesis paper.

PMID- 24137079
TI  - Differences in the number of accelerations between small-sided games and friendly
      matches in soccer.

PMID- 24137080
TI  - Concentric and eccentric: muscle contraction or exercise?

PMID- 24137081
TI  - Reliability of the talk test as a surrogate of ventilatory and respiratory
      compensation thresholds.

PMID- 24137082
TI  - Exercise intensity and energy expenditure of a tabata workout.

PMID- 24137083
TI  - Effects of maximal squat exercise testing on vertical jump performance in
      american college football players.

PMID- 24137085
TI  - 20(th) Anniversary of the Children's Health and Exercise Centre, University of
      Exeter, UK.

PMID- 24137084
TI  - Hemoglobin and hematocrit during an 8 day mountainbike race: a field study.

PMID- 24137086
TI  - Fluid Ingestion Strategies of Competitive Cyclists During 40 km Time Trial
      Competition.

PMID- 24137087
TI  - Use of whole-body vibration as a mode of warming up before counter movement jump.

PMID- 24137089
TI  - Non-musculoskeletal sports medicine learning in family medicine residency
      programs.

PMID- 24137088
TI  - Effects of Microwave Hyperthermia at Two Different Frequencies (434 and 2450 MHz)
      on Human Muscle Temperature.

PMID- 24137090
TI  - Marathon despite unilateral vocal fold paralysis.

PMID- 24137091
TI  - Stress fracture prevalence in elite figure skaters.

PMID- 24137092
TI  - Hormonal responses in heavy training and recovery periods in an elite male
      weightlifter.

PMID- 24137093
TI  - Herbal supplements: cause for concern?

PMID- 24137094
TI  - The Best Athletes in Ancient Rome were Vegetarian!

PMID- 24137095
TI  - Have recent changes to the rugby union laws of scrummage reduced serious cervical
      spine injuries?

PMID- 24137096
TI  - History may be the Best Guide for Determining the Athlete's Dietary Protein
      Needs.

PMID- 24137097
TI  - Importance of automatic external defibrillator: save a life in athletic fields.

PMID- 24137098
TI  - Comparison of metabolic gas analysis between a standard laboratory system and a
      portable device.

PMID- 24137099
TI  - Comments on the paper "the nephrotoxicity risk in rats subjected to heavy muscle
      activity" by gulsen oner and selma cirrik (2009) journal of sports science and
      medicine 8, 481-488" and response of the authors.

PMID- 24137100
TI  - Higher Body Mass Index is a Predictor of Death Among Professional Sumo Wrestlers.

PMID- 24137101
TI  - Karate white belt finger.

PMID- 24137102
TI  - A load-velocity relationship for men and women in overhead throwing performance.

PMID- 24137104
TI  - ISG15 regulates peritoneal macrophages functionality against viral infection.
AB  - Upon viral infection, the production of type I interferon (IFN) and the
      subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral
      state with an important role in the activation of innate and adaptive host immune
      responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced
      antiviral molecule that protects against several viral infections, but the
      mechanism by which ISG15 exerts its antiviral function is not completely
      understood. Here, we report that ISG15 plays an important role in the regulation
      of macrophage responses. ISG15-/- macrophages display reduced activation,
      phagocytic capacity and programmed cell death activation in response to vaccinia
      virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15
      are neither able to phagocyte infected cells nor to block viral infection in co
      culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This
      phenotype is independent of cytokine production and secretion, but clearly
      correlates with impaired activation of the protein kinase AKT in ISG15 knock-out
      (KO) macrophages. Altogether, these results indicate an essential role of ISG15
      in the cellular immune antiviral response and point out that a better
      understanding of the antiviral responses triggered by ISG15 may lead to the
      development of therapies against important human pathogens. 

PMID- 24137105
TI  - Chimeric protein complexes in hybrid species generate novel phenotypes.
AB  - Hybridization between species is an important mechanism for the origin of novel
      lineages and adaptation to new environments. Increased allelic variation and
      modification of the transcriptional network are the two recognized forces
      currently deemed to be responsible for the phenotypic properties seen in hybrids.
      However, since the majority of the biological functions in a cell are carried out
      by protein complexes, inter-specific protein assemblies therefore represent
      another important source of natural variation upon which evolutionary forces can
      act. Here we studied the composition of six protein complexes in two different
      Saccharomyces "sensu stricto" hybrids, to understand whether chimeric
      interactions can be freely formed in the cell in spite of species-specific co
      evolutionary forces, and whether the different types of complexes cause a change
      in hybrid fitness. The protein assemblies were isolated from the hybrids via
      affinity chromatography and identified via mass spectrometry. We found evidence
      of spontaneous chimericity for four of the six protein assemblies tested and we
      showed that different types of complexes can cause a variety of phenotypes in
      selected environments. In the case of TRP2/TRP3 complex, the effect of such
      chimeric formation resulted in the fitness advantage of the hybrid in an
      environment lacking tryptophan, while only one type of parental combination of
      the MBF complex allowed the hybrid to grow under respiratory conditions. These
      phenotypes were dependent on both genetic and environmental backgrounds. This
      study provides empirical evidence that chimeric protein complexes can freely
      assemble in cells and reveals a new mechanism to generate phenotypic novelty and
      plasticity in hybrids to complement the genomic innovation resulting from gene
      duplication. The ability to exchange orthologous members has also important
      implications for the adaptation and subsequent genome evolution of the hybrids in
      terms of pattern of gene loss. 

PMID- 24137103
TI  - Risk factors and outcomes for late presentation for HIV-positive persons in
      Europe: results from the Collaboration of Observational HIV Epidemiological
      Research Europe Study (COHERE).
AB  - BACKGROUND: Few studies have monitored late presentation (LP) of HIV infection
      over the European continent, including Eastern Europe. Study objectives were to
      explore the impact of LP on AIDS and mortality. METHODS AND FINDINGS: LP was
      defined in Collaboration of Observational HIV Epidemiological Research Europe
      (COHERE) as HIV diagnosis with a CD4 count <350/mm(3) or an AIDS diagnosis within
      6 months of HIV diagnosis among persons presenting for care between 1 January
      2000 and 30 June 2011. Logistic regression was used to identify factors
      associated with LP and Poisson regression to explore the impact on AIDS/death.
      84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were
      LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European
      countries (57.0%), and persons originating from Africa (65.1%). LP decreased from
      57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95
      0.97). LP decreased over time in both Central and Northern Europe among
      homosexual men, and male and female heterosexuals, but increased over time for
      female heterosexuals and male intravenous drug users (IDUs) from Southern Europe
      and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred
      during 327,003 person-years of follow-up. In the first year after HIV diagnosis,
      LP was associated with over a 13-fold increased incidence of AIDS/death in
      Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70)
      and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55
      12.43). CONCLUSIONS: LP has decreased over time across Europe, but remains a
      significant issue in the region in all HIV exposure groups. LP increased in male
      IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP
      was associated with an increased rate of AIDS/deaths, particularly in the first
      year after HIV diagnosis, with significant variation across Europe. Earlier and
      more widespread testing, timely referrals after testing positive, and improved
      retention in care strategies are required to further reduce the incidence of LP.

PMID- 24137106
TI  - Differences in neural activation as a function of risk-taking task parameters.
AB  - Despite evidence supporting a relationship between impulsivity and naturalistic
      risk-taking, the relationship of impulsivity with laboratory-based measures of
      risky decision-making remains unclear. One factor contributing to this gap in our
      understanding is the degree to which different risky decision-making tasks vary
      in their details. We conducted an fMRI investigation of the Angling Risk Task
      (ART), which is an improved behavioral measure of risky decision-making. In order
      to examine whether the observed pattern of neural activation was specific to the
      ART or generalizable, we also examined correlates of the Balloon Analog Risk
      Taking (BART) task in the same sample of 23 healthy adults. Exploratory analyses
      were conducted to examine the relationship between neural activation,
      performance, impulsivity and self-reported risk-taking. While activation in a
      valuation network was associated with reward tracking during the ART but not the
      BART, increased fronto-cingulate activation was seen during risky choice trials
      in the BART as compared to the ART. Thus, neural activation during risky decision
      making trials differed between the two tasks, and this observation was likely
      driven by differences in task parameters, namely the absence vs. presence of
      ambiguity and/or stationary vs. increasing probability of loss on the ART and
      BART, respectively. Exploratory association analyses suggest that sensitivity of
      neural response to the magnitude of potential reward during the ART was
      associated with a suboptimal performance strategy, higher scores on a scale of
      dysfunctional impulsivity (DI) and a greater likelihood of engaging in risky
      behaviors, while this pattern was not seen for the BART. Our results suggest that
      the ART is decomposable and associated with distinct patterns of neural
      activation; this represents a preliminary step toward characterizing a behavioral
      measure of risky decision-making that may support a better understanding of
      naturalistic risk-taking. 

PMID- 24137107
TI  - The consequences of subtracting the mean pattern in fMRI multivariate correlation
      analyses.

PMID- 24137109
TI  - Effects of intraventricular methotrexate administration on Cuprizone-induced
      demyelination in mice.
AB  - We previously showed that intrathecal administration of methotrexate slowed
      disability progression in multiple sclerosis (MS) patients with progressive
      disease. In general MS patients with progressive disease respond poorly to anti
      inflammatory therapies. In order to better understand the mechanism by which
      methotrexate is protective in progressive MS, we analyzed its impact on the non
      inflammatory cuprizone-induced demyelination model. When low-dose methotrexate
      was administered intracerebroventricularly it reduced demyelination and
      accumulation of GFAP+ reactive astrocytes in the corpus callosum. Administration
      of methotrexate after the withdrawal of cuprizone neither delayed remyelination
      nor influenced the number of astrocytes in the corpus callosum suggesting that
      methotrexate does not interfere with repair processes in the CNS. Moreover,
      methotrexate increased the expression of IGF1 in vitro and in vivo, a factor
      known to protect oligodendrocytes and limit the activation of astrocytes. Our
      studies show that methotrexate has an impact on pathogenic process in a
      demyelination model whose pathophysiological basis is not primarily related to
      inflammatory mechanisms, similar to neurodegenerative mechanisms associated with
      progressive MS. The pronounced inhibitory influence of methotrexate on the
      accumulation of astrocytes in the corpus callosum suggests that intrathecal
      methotrexate modulates astroglial activation in progressive MS possibly by
      promoting CNS production of IGF1. 

PMID- 24137108
TI  - Programming of neuroendocrine self in the thymus and its defect in the
      development of neuroendocrine autoimmunity.
AB  - For centuries after its first description by Galen, the thymus was considered as
      only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP
      Miller of its essential role in the development of T (thymo-dependent)
      lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500
      million years ago, at the same time or shortly after the emergence of the
      adaptive (acquired) immune system. The thymus may be compared to a small brain or
      a computer highly specialized in the orchestration of central immunological self
      tolerance. This was a necessity for the survival of species, given the potent
      evolutionary pressure imposed by the high risk of autotoxicity inherent in the
      stochastic generation of the diversity of immune cell receptors that characterize
      the adaptive immune response. A new paradigm of "neuroendocrine self-peptides"
      has been proposed, together with the definition of "neuroendocrine self."
      Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs) not
      according to the classic model of neuroendocrine signaling, but are processed for
      presentation by, or in association with, the thymic major histocompatibility
      complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the
      transcription of neuroendocrine genes in TECs. The presentation of self-peptides
      in the thymus is responsible for the clonal deletion of self-reactive T cells,
      which emerge during the random recombination of gene segments that encode
      variable parts of the T cell receptor for the antigen (TCR). At the same time,
      self-antigen presentation in the thymus generates regulatory T (Treg) cells that
      can inhibit, in the periphery, those self-reactive T cells that escaped negative
      selection in the thymus. Several arguments indicate that the origin of
      autoimmunity directed against neuroendocrine glands results primarily from a
      defect in the intrathymic programming of self-tolerance to neuroendocrine
      functions. This defect may be genetic or acquired, for example during an
      enteroviral infection. This novel knowledge of normal and pathologic functions of
      the thymus constitutes a solid basis for the development of a novel type of
      tolerogenic/negative self-vaccination against type 1 diabetes (T1D). 

PMID- 24137110
TI  - Diversity of layer 5 projection neurons in the mouse motor cortex.
AB  - In the primary motor cortex (M1), layer 5 projection neurons signal directly to
      distant motor structures to drive movement. Despite their pivotal position and
      acknowledged diversity these neurons are traditionally separated into broad
      commissural and corticofugal types, and until now no attempt has been made at
      resolving the basis for their diversity. We therefore probed the
      electrophysiological and morphological properties of retrogradely labeled M1
      corticospinal (CSp), corticothalamic (CTh), and commissural projecting
      corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster
      analysis established at least four phenotypes with additional differences between
      lumbar and cervical projecting CSp neurons. Distinguishing parameters included
      the action potential (AP) waveform, firing behavior, the hyperpolarisation
      activated sag potential, sublayer position, and soma and dendrite size. CTh
      neurons differed from CSp neurons in showing spike frequency acceleration and a
      greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise
      rate of all neurons. Temperature influenced spike train behavior in corticofugal
      neurons. At 26 degrees C CTh neurons fired bursts of APs more often than CSp
      neurons, but at 36 degrees C both groups fired regular APs. Our findings provide
      reliable phenotypic fingerprints to identify distinct M1 projection neuron
      classes as a tool to understand their unique contributions to motor function. 

PMID- 24137111
TI  - Direction- and distance-dependent interareal connectivity of pyramidal cell
      subpopulations in the rat frontal cortex.
AB  - The frontal cortex plays an important role in the initiation and execution of
      movements via widespread projections to various cortical and subcortical areas.
      Layer 2/3 (L2/3) pyramidal cells in the frontal cortex send axons mainly to other
      ipsilateral/contralateral cortical areas. Subpopulations of layer 5 (L5)
      pyramidal cells that selectively project to the pontine nuclei or to the
      contralateral cortex [commissural (COM) cells] also target diverse and sometimes
      overlapping ipsilateral cortical areas. However, little is known about target
      area-dependent participation in ipsilateral corticocortical (iCC) connections by
      subclasses of L2/3 and L5 projection neurons. To better understand the functional
      hierarchy between cortical areas, we compared iCC connectivity between the
      secondary motor cortex (M2) and adjacent areas, such as the orbitofrontal and
      primary motor cortices, and distant non-frontal areas, such as the perirhinal and
      posterior parietal cortices. We particularly assessed the laminar distribution of
      iCC cells and fibers, and identified the subtypes of pyramidal cells
      participating in those projections. For connections between M2 and frontal areas,
      L2/3 and L5 cells in both areas contributed to reciprocal projections, which can
      be viewed as "bottom-up" or "top-down" on the basis of their differential
      targeting of cortical lamina. In connections between M2 and non-frontal areas,
      neurons participating in bottom-up and top-down projections were segregated into
      the different layers: bottom-up projections arose primarily from L2/3 cells,
      while top-down projections were dominated by L5 COM cells. These findings suggest
      that selective participation in iCC connections by pyramidal cell subtypes lead
      to directional connectivity between M2 and other cortical areas. Based on these
      findings, we propose a provisional unified framework of interareal hierarchy
      within the frontal cortex, and discuss the interaction of local circuits with
      long-range interareal connections. 

PMID- 24137112
TI  - Germline recombination by conditional gene targeting with Parvalbumin-Cre lines.

PMID- 24137113
TI  - Stress affects theta activity in limbic networks and impairs novelty-induced
      exploration and familiarization.
AB  - Exposure to a novel environment triggers the response of several brain areas that
      regulate emotional behaviors. Here, we studied theta oscillations within the
      hippocampus (HPC)-amygdala (AMY)-medial prefrontal cortex (mPFC) network in
      exploration of a novel environment and subsequent familiarization through
      repeated exposures to that same environment; in addition, we assessed how
      concomitant stress exposure could disrupt this activity and impair both
      behavioral processes. Local field potentials (LFP) were simultaneously recorded
      from dorsal and ventral hippocampus (dHPC and vHPC, respectively), basolateral
      amygdala (BLA) and mPFC in freely behaving rats while they were exposed to a
      novel environment, then repeatedly re-exposed over the course of 3 weeks to that
      same environment and, finally, on re-exposure to a novel unfamiliar environment.
      A longitudinal analysis of theta activity within this circuit revealed a
      reduction of vHPC and BLA theta power and vHPC-BLA theta coherence through
      familiarization which was correlated with a return to normal exploratory behavior
      in control rats. In contrast, a persistent over-activation of the same brain
      regions was observed in stressed rats that displayed impairments in novel
      exploration and familiarization processes. Importantly, we show that stress also
      affected intra-hippocampal synchrony and heightened the coherence between vHPC
      and BLA. In summary, we demonstrate that modulatory theta activity in the
      aforementioned circuit, namely in the vHPC and BLA, is correlated with the
      expression of anxiety in novelty-induced exploration and familiarization in both
      normal and pathological conditions. 

PMID- 24137114
TI  - Neural basis for the ability of atypical antipsychotic drugs to improve cognition
      in schizophrenia.
AB  - Cognitive impairments are considered to largely affect functional outcome in
      patients with schizophrenia, other psychotic illnesses, or mood disorders.
      Specifically, there is much attention to the role of psychotropic compounds
      acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of
      schizophrenia. It is noteworthy that atypical antipsychotic drugs (AAPDs), e.g.,
      clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole,
      perospirone, blonanserin, and lurasidone, have variable affinities for these
      receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting
      particular interests as a potential target for enhancing cognition, based on
      preclinical and clinical evidence. The neural network underlying the ability of 5
      HT1A agonists to treat cognitive impairments of schizophrenia likely includes
      dopamine, glutamate, and gamma-aminobutyric acid neurons. A novel strategy for
      cognitive enhancement in psychosis may be benefited by focusing on energy
      metabolism in the brain. In this context, lactate plays a major role, and has
      been shown to protect neurons against oxidative and other stressors. In
      particular, our data indicate chronic treatment with tandospirone, a partial 5
      HT1A agonist, recover stress-induced lactate production in the prefrontal cortex
      of a rat model of schizophrenia. Recent advances of electrophysiological
      measures, e.g., event-related potentials, and their imaging have provided
      insights into facilitative effects on cognition of some AAPDs acting directly or
      indirectly on 5-HT1A receptors. These findings are expected to promote the
      development of novel therapeutics for the improvement of functional outcome in
      people with schizophrenia. 

PMID- 24137115
TI  - Sex-specific positive and negative consequences of avoidance training during
      childhood on adult active avoidance learning in mice.
AB  - In humans and animals cognitive training during childhood plays an important role
      in shaping neural circuits and thereby determines learning capacity later in
      life. Using a negative feedback learning paradigm, the two-way active avoidance
      (TWA) learning, we aimed to investigate in mice (i) the age-dependency of TWA
      learning, (ii) the consequences of pretraining in childhood on adult learning
      capacity and (iii) the impact of sex on the learning paradigm in mice. Taken
      together, we show here for the first time that the beneficial or detrimental
      outcome of pretraining in childhood depends on the age during which TWA training
      is encountered, indicating that different, age-dependent long-term "memory
      traces" might be formed, which are recruited during adult TWA training and
      thereby either facilitate or impair adult TWA learning. While pretraining during
      infancy results in learning impairment in adulthood, pretraining in late
      adolescence improved avoidance learning. The experiments revealed a clear sex
      difference in the group of late-adolescent mice: female mice showed better
      avoidance learning during late adolescence compared to males, and the beneficial
      impact of late-adolescent pretraining on adult learning was more pronounced in
      females compared to males. 

PMID- 24137117
TI  - Looking for trouble: a description of oculomotor search strategies during live
      CCTV operation.
AB  - Recent research has begun to address how CCTV operators in the modern control
      room attempt to search for crime (e.g., Howard et al., 2011). However, an often
      neglected element of the CCTV task is that the operators have at their disposal a
      multiplexed wall of scenes, and a single spot-monitor on which they can select
      any of these feeds for inspection. Here we examined how 2 trained CCTV operators
      used these sources of information to search from crime during a morning,
      afternoon, and night-time shift. We found that they spent surprisingly little
      time viewing the multiplex wall, instead preferentially spending most of their
      time searching on the single-scene spot-monitor. Such search must require a
      sophisticated understanding of the surveilled environment, as the operators must
      make their selection of which screen to view based on their prediction of where
      crime is likely to occur. This seems to be reflected in the difference in the
      screens that they selected to view at different times of the day. For example,
      night-clubs received close monitoring at night, but were seldom viewed in mid
      morning. Such narrowing of search based on a contextual understanding of an
      environment is not a new idea (e.g., Torralba et al., 2006), and appears to
      contribute to operator's selection strategy. This research prompts new questions
      regarding the nature of representation that operators have of their environment,
      and how they might develop expectation-based search strategies to countermand the
      demands of the large influx of visual information. Future research should ensure
      not to neglect examination of operator behavior "in the wild" (Hutchins, 1995a),
      as such insights are difficult to gain from laboratory based paradigms alone. 

PMID- 24137116
TI  - The embodied transcendental: a Kantian perspective on neurophenomenology.
AB  - Neurophenomenology is a research programme aimed at bridging the explanatory gap
      between first-person subjective experience and neurophysiological third-person
      data, through an embodied and enactive approach to the biology of consciousness.
      The present proposal attempts to further characterize the bodily basis of the
      mind by adopting a naturalistic view of the phenomenological concept of
      intentionality as the a priori invariant character of any lived experience.
      Building on the Kantian definition of transcendentality as "what concerns the a
      priori formal structures of the subject's mind" and as a precondition for the
      very possibility of human knowledge, we will suggest that this transcendental
      core may in fact be rooted in biology and can be examined within an extension of
      the theory of autopoiesis. The argument will be first clarified by examining its
      application to previously proposed elementary autopoietic models, to the
      bacterium, and to the immune system; it will be then further substantiated and
      illustrated by examining the mirror-neuron system and the default mode network as
      biological instances exemplifying the enactive nature of knowledge, and by
      discussing the phenomenological aspects of selected neurological conditions
      (neglect, schizophrenia). In this context, the free-energy principle proposed
      recently by Karl Friston will be briefly introduced as a rigorous, neurally
      plausible framework that seems to accomodate optimally these ideas. While our
      approach is biologically-inspired, we will maintain that lived first-person
      experience is still critical for a better understanding of brain function, based
      on our argument that the former and the latter share the same transcendental
      structure. Finally, the role that disciplined contemplative practices can play to
      this aim, and an interpretation of the cognitive processes taking place during
      meditation under this perspective, will be also discussed. 

PMID- 24137118
TI  - Expertise in action observation: recent neuroimaging findings and future
      perspectives.

PMID- 24137119
TI  - Motor extinction: a deficit of attention or intention?
AB  - Motor extinction refers to a deficit of motor production on the side opposite a
      brain lesion that either only becomes apparent or disproportionately worsens
      during bilateral motor activity. It may arise due either to a contralesional
      deficit in setting the motor activation level (an intentional deficit) or a
      deficit in contralesional awareness of the sensory consequences of movement (an
      attentional deficit). In this study, we investigate the nature of motor
      extinction in a patient (LR) with a right fronto-temporal lesion through the
      kinematic analysis of unimanual and bimanual circle-drawing movements. While the
      ipsi- and contralesional limbs performed comparably for unimanual movements, the
      contralesional limb demonstrated marked bradykinesia and hypometria during
      bimanual movements. Furthermore, these deficits were not overcome when visual
      feedback of the contralesional limb was provided (Experiment 1). However, when
      performing bimanual movements in the presence of a visual template (Experiment
      2), LR was able to overcome the contralesional hypometria but not the
      bradykinesia which proved intractable across both experiments. Both the
      bradykinesia and hypometria could result from an intentional deficit of motor
      production. However, in Experiment 2, LR also demonstrated an abnormal level of
      positional drift in the contralesional limb for bimanual movements indicative of
      an additional attentional deficit. We conclude that LR's presentation of motor
      extinction is the result of a primary intentional deficit and a secondary
      attentional deficit. 

PMID- 24137120
TI  - Applying the neuroscience of creativity to creativity training.
AB  - This article investigates how neuroscience in general, and neuroscience of
      creativity in particular, can be used in teaching "applied creativity" and the
      usefulness of this approach to creativity training. The article is based on
      empirical data and our experiences from the Applied NeuroCreativity (ANC)
      program, taught at business schools in Denmark and Canada. In line with previous
      studies of successful creativity training programs the ANC participants are first
      introduced to cognitive concepts of creativity, before applying these concepts to
      a relevant real world creative problem. The novelty in the ANC program is that
      the conceptualization of creativity is built on neuroscience, and a crucial
      aspect of the course is giving the students a thorough understanding of the
      neuroscience of creativity. Previous studies have reported that the
      conceptualization of creativity used in such training is of major importance for
      the success of the training, and we believe that the neuroscience of creativity
      offers a novel conceptualization for creativity training. Here we present
      pre/post-training tests showing that ANC students gained more fluency in
      divergent thinking (a traditional measure of trait creativity) than those in
      highly similar courses without the neuroscience component, suggesting that
      principles from neuroscience can contribute effectively to creativity training
      and produce measurable results on creativity tests. The evidence presented
      indicates that the inclusion of neuroscience principles in a creativity course
      can in 8 weeks increase divergent thinking skills with an individual relative
      average of 28.5%. 

PMID- 24137122
TI  - Reference frame selection in dialog: priming or preference?
AB  - We investigate effects of priming and preference on frame of reference (FOR)
      selection in dialog. In a first study, we determine FOR preferences for specific
      object configurations to establish a baseline. In a second study, we focus on the
      selection of the relative or the intrinsic FOR in dialog using the same stimuli
      and addressing the questions whether (a) interlocutors prime each other to use
      the same FOR consistently or (b) the preference for the intrinsic FOR
      predominates priming effects. Our results show effects of priming (more use of
      the relative FOR) and a decreased preference for the intrinsic FOR. However, as
      FOR selection did not have an effect on target trial accuracy, neither effect
      alone represents the key to successful communication in this domain. Rather, we
      found that successful communication depended on the adaptation of strategies
      between interlocutors: the more the interlocutors adapted to each other's
      strategies, the more successful they were. 

PMID- 24137121
TI  - Speech serial control in healthy speakers and speakers with hypokinetic or ataxic
      dysarthria: effects of sequence length and practice.
AB  - The current study investigated the processes responsible for selection of sounds
      and syllables during production of speech sequences in 10 adults with hypokinetic
      dysarthria from Parkinson's disease, five adults with ataxic dysarthria, and 14
      healthy control speakers. Speech production data from a choice reaction time task
      were analyzed to evaluate the effects of sequence length and practice on speech
      sound sequencing. Speakers produced sequences that were between one and five
      syllables in length over five experimental runs of 60 trials each. In contrast to
      the healthy speakers, speakers with hypokinetic dysarthria demonstrated
      exaggerated sequence length effects for both inter-syllable intervals (ISIs) and
      speech error rates. Conversely, speakers with ataxic dysarthria failed to
      demonstrate a sequence length effect on ISIs and were also the only group that
      did not exhibit practice-related changes in ISIs and speech error rates over the
      five experimental runs. The exaggerated sequence length effects in the
      hypokinetic speakers with Parkinson's disease are consistent with an impairment
      of action selection during speech sequence production. The absent length effects
      observed in the speakers with ataxic dysarthria is consistent with previous
      findings that indicate a limited capacity to buffer speech sequences in advance
      of their execution. In addition, the lack of practice effects in these speakers
      suggests that learning-related improvements in the production rate and accuracy
      of speech sequences involves processing by structures of the cerebellum.
      Together, the current findings inform models of serial control for speech in
      healthy speakers and support the notion that sequencing deficits contribute to
      speech symptoms in speakers with hypokinetic or ataxic dysarthria. In addition,
      these findings indicate that speech sequencing is differentially impaired in
      hypokinetic and ataxic dysarthria. 

PMID- 24137123
TI  - Abnormal perilesional BOLD signal is not correlated with stroke patients'
      behavior.
AB  - Several functional magnetic resonance imaging (fMRI) studies of acute stroke have
      reported that patients with behavioral deficits show abnormal signal in intact
      regions of the damaged hemisphere close to the lesion border relative to
      homologous regions of the patient's intact hemisphere (causing an
      interhemispheric imbalance) as well as analogous regions in healthy controls.
      These effects have been interpreted as demonstrating a causal relationship
      between the abnormal fMRI signal and the pathological behavior. Here we explore
      an alternative explanation: perhaps the abnormal Blood-Oxygenation Level
      Dependent (BOLD) fMRI signal is merely a function of distance from the acute
      lesion. To investigate this hypothesis, we examined three patients with an acute
      right hemisphere cortical stroke who did not show any overt behavioral deficits,
      as well as nine healthy elderly controls. We acquired fMRI data while the
      participants performed a simple visual orientation judgment task. In patients, we
      observed an abnormal interhemispheric balance consisting of lower levels of
      percent signal change in perilesional areas of the damaged hemisphere relative to
      homologous areas in neurologically healthy controls. This suggests that the
      physiological changes and corresponding interhemispheric imbalance detected by
      fMRI BOLD in acute stroke observed close to the lesion border may not necessarily
      reflect changes in the neural function, nor necessarily influence the
      individuals' (e.g., attentional) behavior. 

PMID- 24137124
TI  - Fusion of fNIRS and fMRI data: identifying when and where hemodynamic signals are
      changing in human brains.
AB  - In this study we implemented a new imaging method to fuse functional near
      infrared spectroscopy (fNIRS) measurements and functional magnetic resonance
      imaging (fMRI) data to reveal the spatiotemporal dynamics of the hemodynamic
      responses with high spatiotemporal resolution across the brain. We evaluated this
      method using multimodal data acquired from human right finger tapping tasks. And
      we found the proposed method is able to clearly identify from the linked
      components of fMRI and fNIRS where and when the hemodynamic signals are changing.
      In particular, the estimated associations between fNIRS and fMRI will be
      displayed as time varying spatial fMRI maps along with the fNIRS time courses. In
      addition, the joint components between fMRI and fNIRS are combined together to
      generate full spatiotemporal "snapshots" and movies, which provides an excellent
      way to examine the dynamic interplay between hemodynamic fNIRS and fMRI
      measurements. 

PMID- 24137125
TI  - A transcranial magnetic stimulation study of the effect of visual orientation on
      the putative human mirror neuron system.
AB  - Mirror neurons are a class of motor neuron that are active during both the
      performance and observation of behavior, and have been implicated in
      interpersonal understanding. There is evidence to suggest that the mirror
      response is modulated by the perspective from which an action is presented (e.g.,
      egocentric or allocentric). Most human research, however, has only examined this
      when presenting intransitive actions. Twenty-three healthy adult participants
      completed a transcranial magnetic stimulation experiment that assessed
      corticospinal excitability whilst viewing transitive hand gestures from both
      egocentric (i.e., self) and allocentric (i.e., other) viewpoints. Although action
      observation was associated with increases in corticospinal excitability
      (reflecting putative human mirror neuron activity), there was no effect of visual
      perspective. These findings are discussed in the context of contemporary theories
      of mirror neuron ontogeny, including models concerning associative learning and
      evolutionary adaptation. 

PMID- 24137126
TI  - Fast monitoring of epileptic seizures using recurrence time statistics of
      electroencephalography.
AB  - Epilepsy is a relatively common brain disorder which may be very debilitating.
      Currently, determination of epileptic seizures often involves tedious, time
      consuming visual inspection of electroencephalography (EEG) data by medical
      experts. To better monitor seizures and make medications more effective, we
      propose a recurrence time based approach to characterize brain electrical
      activity. Recurrence times have a number of distinguished properties that make it
      very effective for forewarning epileptic seizures as well as studying propagation
      of seizures: (1) recurrence times amount to periods of periodic signals, (2)
      recurrence times are closely related to information dimension, Lyapunov exponent,
      and Kolmogorov entropy of chaotic signals, (3) recurrence times embody Shannon
      and Renyi entropies of random fields, and (4) recurrence times can readily detect
      bifurcation-like transitions in dynamical systems. In particular, property (4)
      dictates that unlike many other non-linear methods, recurrence time method does
      not require the EEG data be chaotic and/or stationary. Moreover, the method only
      contains a few parameters that are largely signal-independent, and hence, is very
      easy to use. The method is also very fast-it is fast enough to on-line process
      multi-channel EEG data with a typical PC. Therefore, it has the potential to be
      an excellent candidate for real-time monitoring of epileptic seizures in a
      clinical setting. 

PMID- 24137127
TI  - Quantifying network properties in multi-electrode recordings: spatiotemporal
      characterization and inter-trial variation of evoked gamma oscillations in mouse
      somatosensory cortex in vitro.
AB  - Linking the structural connectivity of brain circuits to their cooperative
      dynamics and emergent functions is a central aim of neuroscience research. Graph
      theory has recently been applied to study the structure-function relationship of
      networks, where dynamical similarity of different nodes has been turned into a
      "static" functional connection. However, the capability of the brain to adapt,
      learn and process external stimuli requires a constant dynamical functional
      rewiring between circuitries and cell assemblies. Hence, we must capture the
      changes of network functional connectivity over time. Multi-electrode array data
      present a unique challenge within this framework. We study the dynamics of gamma
      oscillations in acute slices of the somatosensory cortex from juvenile mice
      recorded by planar multi-electrode arrays. Bursts of gamma oscillatory activity
      lasting a few hundred milliseconds could be initiated only by brief trains of
      electrical stimulations applied at the deepest cortical layers and simultaneously
      delivered at multiple locations. Local field potentials were used to study the
      spatio-temporal properties and the instantaneous synchronization profile of the
      gamma oscillatory activity, combined with current source density (CSD) analysis.
      Pair-wise differences in the oscillation phase were used to determine the
      presence of instantaneous synchronization between the different sites of the
      circuitry during the oscillatory period. Despite variation in the duration of the
      oscillatory response over successive trials, they showed a constant average
      power, suggesting that the rate of expenditure of energy during the gamma bursts
      is consistent across repeated stimulations. Within each gamma burst, the
      functional connectivity map reflected the columnar organization of the neocortex.
      Over successive trials, an apparently random rearrangement of the functional
      connectivity was observed, with a more stable columnar than horizontal
      organization. This work reveals new features of evoked gamma oscillations in
      developing cortex. 

PMID- 24137128
TI  - The Serum Concentration of the Calcium Binding Protein S100B is Positively
      Associated with Cognitive Performance in Older Adults.
AB  - S100B is a calcium binding peptide produced predominantly by astroglial cells in
      the central nervous system. S100B paradoxically has neurotrophic and apoptotic
      effects, dependent on extracellular concentration. This study investigated the
      relationship between serum S100B levels and neuropsychological performance across
      a range of cognitive domains in healthy older aged adults. A cohort of 219
      participants between the ages of 43 and 84 years (141 female) were recruited.
      Subjects provided a fasting blood sample for S100B measurement (Mean = 0.24
      ng/mL, SD = 0.14) and completed a battery of neuropsychological tests. S100B
      concentrations (both with and without the covariates of age and sex) were
      positively associated with the following measures of cognitive performance: digit
      symbol coding, Stroop test, and measures of verbal ability. The results from this
      study show that serum S100B is positively associated with better cognitive
      performance in healthy older adults. 

PMID- 24137129
TI  - Age-related dedifferentiation of cognitive and motor slowing: insight from the
      comparison of Hick-Hyman and Fitts' laws.
AB  - The present study aimed to determine whether the general slowing hypothesis (GSH)
      could be extended to the motor domain by comparing cognitive and motor age
      related slowing. To achieve this objective, we compared the slopes of Hick
      Hyman's law and Fitts' law, in young and older adults. The general hypothesis was
      that, due to the dedifferentiation of cognitive and motor neural resources during
      aging, the slopes of Hick-Hyman's law and Fitts' law should become closer, if not
      similar, in older adults. Ten young adults (mean age = 26 +/- 3 years) and 14
      older adults (mean age = 78 +/- 7 years) participated in the experiment. They had
      to perform a discrete rapid-aiming task and a reaction time (RT) task. In the
      aiming task, five index of difficulty (ID) levels were used (from three to seven
      bits by increments of 1.0 bit). Task difficulty was scaled via the manipulation
      of target distance from home position. In the RT task, five IDs were selected: 0,
      1, 2, 3, and 4 bits, with incompatible S-R associations. RT and movement times
      were recorded. Efficiency and Brinley regression functions were calculated. Age
      related slowing ratios were estimated. Response times increased in both tasks in
      older adults. The slopes of Hick-Hyman's law and Fitts' law were steeper in older
      adults than in young participants. In young participants, the slope of Hick
      Hyman's law was smaller than that of Fitts' law. In older adults, no difference
      was found. Slowing ratios observed in both tasks were equivalent. The present
      results extended the GSH to the motor domain. They suggested that, due to
      dedifferentiation of cognitive and motor neural resources, decrease in processing
      speed acts as a common cause to behavioral slowing in both cognitive and motor
      tasks. 

PMID- 24137131
TI  - Functional implications of Drosophila insulin-like peptides in metabolism, aging,
      and dietary restriction.
AB  - The neuroendocrine architecture and insulin/insulin-like signaling (IIS) events
      in Drosophila are remarkably conserved. As IIS pathway governs growth and
      development, metabolism, reproduction, stress response, and longevity; temporal,
      spatial, and nutrient regulation of dilps encoding Drosophila insulin-like
      peptides (DILPs) provides potential mechanisms in modulating IIS. Of eight DILPs
      (DILP1-8) identified, recent studies have furthered our understanding of
      physiological roles of DILP2, DILP3, DILP5, and DILP6 in metabolism, aging, and
      responses to dietary restriction (DR), which will be the focus of this review.
      While the DILP producing IPCs of the brain secrete DILP2, 3, and 5, fat body
      produces DILP6. Identification of factors that influence dilp expression and DILP
      secretion has provided insight into the intricate regulatory mechanisms
      underlying transcriptional regulation of those genes and the activity of each
      peptide. Studies involving loss-of-function dilp mutations have defined the roles
      of DILP2 and DILP6 in carbohydrate and lipid metabolism, respectively. While
      DILP3 has been implicated to modulate lipid metabolism, a metabolic role for
      DILP5 is yet to be determined. Loss of dilp2 or adult fat body specific
      expression of dilp6 has been shown to extend lifespan, establishing their roles
      in longevity regulation. The exact role of DILP3 in aging awaits further
      clarification. While DILP5 has been shown associated with DR-mediated lifespan
      extension, contradictory evidence that precludes a direct involvement of DILP5 in
      DR exists. This review highlights recent findings on the importance of conserved
      DILPs in metabolic homeostasis, DR, and aging, providing strong evidence for the
      use of DILPs in modeling metabolic disorders such as diabetes and
      hyperinsulinemia in the fly that could further our understanding of the
      underlying processes and identify therapeutic strategies to treat them. 

PMID- 24137130
TI  - MicroRNAs in skeletal muscle and their regulation with exercise, ageing, and
      disease.
AB  - Skeletal muscle makes up approximately 40% of the total body mass, providing
      structural support and enabling the body to maintain posture, to control motor
      movements and to store energy. It therefore plays a vital role in whole body
      metabolism. Skeletal muscle displays remarkable plasticity and is able to alter
      its size, structure and function in response to various stimuli; an essential
      quality for healthy living across the lifespan. Exercise is an important
      stimulator of extracellular and intracellular stress signals that promote
      positive adaptations in skeletal muscle. These adaptations are controlled by
      changes in gene transcription and protein translation, with many of these
      molecules identified as potential therapeutic targets to pharmacologically
      improve muscle quality in patient groups too ill to exercise. MicroRNAs (miRNAs)
      are recently identified regulators of numerous gene networks and pathways and
      mainly exert their effect by binding to their target messenger RNAs (mRNAs),
      resulting in mRNA degradation or preventing protein translation. The role of
      exercise as a regulatory stimulus of skeletal muscle miRNAs is now starting to be
      investigated. This review highlights our current understanding of the regulation
      of skeletal muscle miRNAs with exercise and disease as well as how they may
      control skeletal muscle health. 

PMID- 24137132
TI  - ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in
      the collecting duct.
AB  - ATP in the renal tubular fluid is an important regulator of salt and water
      reabsorption via purinergic calcium signaling that involves the P2Y2 receptor,
      ENaC, and AQP2. Recently, we have shown that connexin (Cx) 30 hemichannels are
      localized to the non-junctional apical membrane of cells in the distal nephron
      collecting duct (CD) and release ATP into the tubular fluid upon mechanical
      stimuli, leading to reduced salt and water reabsorption. Cx30(-/-) mice show salt
      dependent elevations in BP and impaired pressure-natriuresis. Thus, we
      hypothesized that increased tubular flow rate leads to Cx30-dependent purinergic
      intracellular calcium ([Ca(2+)]i) signaling in the CD. Cortical CDs (CCDs) from
      wild type and Cx30(-/-) mice were freshly dissected and microperfused in vitro.
      Using confocal fluorescence imaging and the calcium-sensitive fluorophore pair
      Fluo-4 and Fura Red, we found that increasing tubular flow rate from 2 to 20
      nl/min caused a significant 2.1-fold elevation in [Ca(2+)]i in wild type CCDs.
      This response was blunted in Cx30(-/-) CCDs ([Ca(2+)]i increased only 1.2-fold, p
      < 0.0001 vs. WT, n = 6 each). To further test our hypothesis we performed CD
      [Ca(2+)]i imaging in intact mouse kidneys in vivo using multiphoton microscopy
      and micropuncture delivery of the calcium-sensitive fluorophore Rhod-2. We found
      intrinsic, spontaneous [Ca(2+)]i oscillations in free-flowing CDs of wild type
      but not Cx30(-/-) mice. The [Ca(2+)]i oscillations were sensitive also to P2
      receptor inhibition by suramin. Taken together, these data confirm that
      mechanosensitive Cx30 hemichannels mediate tubular ATP release and purinergic
      calcium signaling in the CD which mechanism plays an important role in the
      regulation of CD salt and water reabsorption. 

PMID- 24137134
TI  - Does Cannabidiol Protect Against Adverse Psychological Effects of THC?
AB  - The recreational use of cannabis can have persistent adverse effects on mental
      health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent
      of cannabis, and most, if not all, of the effects associated with the use of
      cannabis are caused by THC. Recent studies have suggested a possible protective
      effect of another cannabinoid, cannabidiol (CBD). A literature search was
      performed in the bibliographic databases PubMed, PsycINFO, and Web of Science
      using the keyword "cannabidiol." After removing duplicate entries, 1295 unique
      titles remained. Based on the titles and abstracts, an initial selection was
      made. The reference lists of the publications identified in this manner were
      examined for additional references. Cannabis is not a safe drug. Depending on how
      often someone uses, the age of onset, the potency of the cannabis that is used
      and someone's individual sensitivity, the recreational use of cannabis may cause
      permanent psychological disorders. Most recreational users will never be faced
      with such persistent mental illness, but in some individuals cannabis use leads
      to undesirable effects: cognitive impairment, anxiety, paranoia, and increased
      risks of developing chronic psychosis or drug addiction. Studies examining the
      protective effects of CBD have shown that CBD can counteract the negative effects
      of THC. However, the question remains of how the laboratory results translate to
      the types of cannabis that are encountered by real-world recreational users. 

PMID- 24137133
TI  - Heart rate variability in normal and pathological sleep.
AB  - Sleep is a physiological process involving different biological systems, from
      molecular to organ level; its integrity is essential for maintaining health and
      homeostasis in human beings. Although in the past sleep has been considered a
      state of quiet, experimental and clinical evidences suggest a noteworthy
      activation of different biological systems during sleep. A key role is played by
      the autonomic nervous system (ANS), whose modulation regulates cardiovascular
      functions during sleep onset and different sleep stages. Therefore, an interest
      on the evaluation of autonomic cardiovascular control in health and disease is
      growing by means of linear and non-linear heart rate variability (HRV) analyses.
      The application of classical tools for ANS analysis, such as HRV during
      physiological sleep, showed that the rapid eye movement (REM) stage is
      characterized by a likely sympathetic predominance associated with a vagal
      withdrawal, while the opposite trend is observed during non-REM sleep. More
      recently, the use of non-linear tools, such as entropy-derived indices, have
      provided new insight on the cardiac autonomic regulation, revealing for instance
      changes in the cardiovascular complexity during REM sleep, supporting the
      hypothesis of a reduced capability of the cardiovascular system to deal with
      stress challenges. Interestingly, different HRV tools have been applied to
      characterize autonomic cardiac control in different pathological conditions, from
      neurological sleep disorders to sleep disordered breathing (SDB). In summary,
      linear and non-linear analysis of HRV are reliable approaches to assess changes
      of autonomic cardiac modulation during sleep both in health and diseases. The use
      of these tools could provide important information of clinical and prognostic
      relevance. 

PMID- 24137135
TI  - A Generalized ideal observer model for decoding sensory neural responses.
AB  - We show that many ideal observer models used to decode neural activity can be
      generalized to a conceptually and analytically simple form. This enables us to
      study the statistical properties of this class of ideal observer models in a
      unified manner. We consider in detail the problem of estimating the performance
      of this class of models. We formulate the problem de novo by deriving two
      equivalent expressions for the performance and introducing the corresponding
      estimators. We obtain a lower bound on the number of observations (N) required
      for the estimate of the model performance to lie within a specified confidence
      interval at a specified confidence level. We show that these estimators are
      unbiased and consistent, with variance approaching zero at the rate of 1/N. We
      find that the maximum likelihood estimator for the model performance is not
      guaranteed to be the minimum variance estimator even for some simple parametric
      forms (e.g., exponential) of the underlying probability distributions. We discuss
      the application of these results for designing and interpreting
      neurophysiological experiments that employ specific instances of this ideal
      observer model. 

PMID- 24137136
TI  - Perceptual estimation obeys Occam's razor.
AB  - Theoretical models of unsupervised category learning postulate that humans
      "invent" categories to accommodate new patterns, but tend to group stimuli into a
      small number of categories. This "Occam's razor" principle is motivated by
      normative rules of statistical inference. If categories influence perception,
      then one should find effects of category invention on simple perceptual
      estimation. In a series of experiments, we tested this prediction by asking
      participants to estimate the number of colored circles on a computer screen, with
      the number of circles drawn from a color-specific distribution. When the
      distributions associated with each color overlapped substantially, participants'
      estimates were biased toward values intermediate between the two means,
      indicating that subjects ignored the color of the circles and grouped different
      colored stimuli into one perceptual category. These data suggest that humans
      favor simpler explanations of sensory inputs. In contrast, when the distributions
      associated with each color overlapped minimally, the bias was reduced (i.e., the
      estimates for each color were closer to the true means), indicating that sensory
      evidence for more complex explanations can override the simplicity bias. We
      present a rational analysis of our task, showing how these qualitative patterns
      can arise from Bayesian computations. 

PMID- 24137137
TI  - Decomposing the roles of perseveration and expected value representation in
      models of the Iowa gambling task.
AB  - Models of human behavior in the Iowa Gambling Task (IGT) have played a pivotal
      role in accounting for behavioral differences during decision-making. One
      critical difference between models that have been used to account for behavior in
      the IGT is the inclusion or exclusion of the assumption that participants tend to
      persevere, or stay with the same option over consecutive trials. Models that
      allow for this assumption include win-stay-lose-shift (WSLS) models and
      reinforcement learning (RL) models that include a decay learning rule where
      expected values for each option decay as they are chosen less often. One
      shortcoming of RL models that have included decay rules is that the tendency to
      persevere by sticking with the same option has been conflated with the tendency
      to select the option with the highest expected value because a single term is
      used to represent both of these tendencies. In the current work we isolate the
      tendencies to perseverate and to select the option with the highest expected
      value by including them as separate terms in a Value-Plus-Perseveration (VPP) RL
      model. Overall the VPP model provides a better fit to data from a large group of
      participants than models that include a single term to account for both
      perseveration and the representation of expected value. Simulations of each model
      show that the VPP model's simulated choices most closely resemble the decision
      making behavior of human subjects. In addition, we also find that parameter
      estimates of loss aversion are more strongly correlated with performance when
      perseverative tendencies and expected value representations are decomposed as
      separate terms within the model. The results suggest that the tendency to
      persevere and the tendency to select the option that leads to the best net payoff
      are central components of decision-making behavior in the IGT. Future work should
      use this model to better examine decision-making behavior. 

PMID- 24137139
TI  - Neuroticism explains unwanted variance in Implicit Association Tests of
      personality: possible evidence for an affective valence confound.
AB  - Meta-analytic data highlight the value of the Implicit Association Test (IAT) as
      an indirect measure of personality. Based on evidence suggesting that confounding
      factors such as cognitive abilities contribute to the IAT effect, this study
      provides a first investigation of whether basic personality traits explain
      unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the
      Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means
      of structural equation modeling (SEM), latent Big-Five personality factors (based
      on self- and peer-report) were estimated and their predictive value for unwanted
      variance in the IAT was examined. In a first analysis, unwanted variance was
      defined in the sense of method-specific variance which may result from
      differences in task demands between the two IAT block conditions and which can be
      mirrored by the absolute size of the IAT effects. In a second analysis, unwanted
      variance was examined in a broader sense defined as those systematic variance
      components in the raw IAT scores that are not explained by the latent implicit
      personality factors. In contrast to the absolute IAT scores, this also considers
      biases associated with the direction of IAT effects (i.e., whether they are
      positive or negative in sign), biases that might result, for example, from the
      IAT's stimulus or category features. None of the explicit Big-Five factors was
      predictive for method-specific variance in the IATs (first analysis). However,
      when considering unwanted variance that goes beyond pure method-specific variance
      (second analysis), a substantial effect of neuroticism occurred that may have
      been driven by the affective valence of IAT attribute categories and the
      facilitated processing of negative stimuli, typically associated with
      neuroticism. The findings thus point to the necessity of using attribute category
      labels and stimuli of similar affective valence in personality IATs to avoid
      confounding due to recoding. 

PMID- 24137138
TI  - Iowa Gambling Task (IGT): twenty years after - gambling disorder and IGT.
AB  - The Iowa Gambling Task (IGT) involves probabilistic learning via monetary rewards
      and punishments, where advantageous task performance requires subjects to forego
      potential large immediate rewards for small longer-term rewards to avoid larger
      losses. Pathological gamblers (PG) perform worse on the IGT compared to controls,
      relating to their persistent preference toward high, immediate, and uncertain
      rewards despite experiencing larger losses. In this contribution, we review
      studies that investigated processes associated with poor IGT performance in PG.
      Findings from these studies seem to fit with recent neurocognitive models of
      addiction, which argue that the diminished ability of addicted individuals to
      ponder short-term against long-term consequences of a choice may be the product
      of an hyperactive automatic attentional and memory system for signaling the
      presence of addiction-related cues (e.g., high uncertain rewards associated with
      disadvantageous decks selection during the IGT) and for attributing to such cues
      pleasure and excitement. This incentive-salience associated with gambling-related
      choice in PG may be so high that it could literally "hijack" resources ["hot"
      executive functions (EFs)] involved in emotional self-regulation and necessary to
      allow the enactment of further elaborate decontextualized problem-solving
      abilities ("cool" EFs). A framework for future research is also proposed, which
      highlights the need for studies examining how these processes contribute
      specifically to the aberrant choice profile displayed by PG on the IGT. 

PMID- 24137140
TI  - Do you see what I hear? Vantage point preference and visual dominance in a time
      space synaesthete.
AB  - Time-space synaesthetes "see" time units organized in a spatial form. While the
      structure might be invariant for most synaesthetes, the perspective by which some
      view their calendar is somewhat flexible. One well-studied synaesthete L adopts
      different viewpoints for months seen vs. heard. Interestingly, L claims to prefer
      her auditory perspective, even though the month names are represented visually
      upside down. To verify this, we used a spatial-cueing task that included
      audiovisual month cues. These cues were either congruent with L's preferred
      "auditory" viewpoint (auditory-only and auditory + month inverted) or incongruent
      (upright visual-only and auditory + month upright). Our prediction was that L
      would show enhanced cueing effects (larger response time difference between valid
      and invalid targets) following the audiovisual congruent cues since both elicit
      the "preferred" auditory perspective. Also, when faced with conflicting cues, we
      predicted L would choose the preferred auditory perspective over the visual
      perspective. As we expected, L did show enhanced cueing effects following the
      audiovisual congruent cues that corresponded with her preferred auditory
      perspective, but that the visual perspective dominated when L was faced with both
      viewpoints simultaneously. The results are discussed with relation to the
      reification hypothesis of sequence space synaesthesia (Eagleman, 2009). 

PMID- 24137141
TI  - Age-related differences in affective responses to and memory for emotions
      conveyed by music: a cross-sectional study.
AB  - There is mounting evidence that aging is associated with the maintenance of
      positive affect and the decrease of negative affect to ensure emotion regulation
      goals. Previous empirical studies have primarily focused on a visual or
      autobiographical form of emotion communication. To date, little investigation has
      been done on musical emotions. The few studies that have addressed aging and
      emotions in music were mainly interested in emotion recognition, thus leaving
      unexplored the question of how aging may influence emotional responses to and
      memory for emotions conveyed by music. In the present study, eighteen older (60
      84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the
      strength of their experienced emotion on happy, peaceful, sad, and scary musical
      excerpts (Vieillard et al., 2008) while facial muscle activity was recorded.
      Participants then performed an incidental recognition task followed by a task in
      which they judged to what extent they experienced happiness, peacefulness,
      sadness, and fear when listening to music. Compared to younger adults, older
      adults (a) reported a stronger emotional reactivity for happiness than other
      emotion categories, (b) showed an increased zygomatic activity for scary stimuli,
      (c) were more likely to falsely recognize happy music, and (d) showed a decrease
      in their responsiveness to sad and scary music. These results are in line with
      previous findings and extend them to emotion experience and memory recognition,
      corroborating the view of age-related changes in emotional responses to music in
      a positive direction away from negativity. 

PMID- 24137142
TI  - Art and science: how musical training shapes the brain.
AB  - What makes a musician? In this review, we discuss innate and experience-dependent
      factors that mold the musician brain in addition to presenting new data in
      children that indicate that some neural enhancements in musicians unfold with
      continued training over development. We begin by addressing effects of training
      on musical expertise, presenting neural, perceptual, and cognitive evidence to
      support the claim that musicians are shaped by their musical training regimes.
      For example, many musician-advantages in the neural encoding of sound, auditory
      perception, and auditory-cognitive skills correlate with their extent of musical
      training, are not observed in young children just initiating musical training,
      and differ based on the type of training pursued. Even amidst innate
      characteristics that contribute to the biological building blocks that make up
      the musician, musicians demonstrate further training-related enhancements through
      extensive education and practice. We conclude by reviewing evidence from
      neurobiological and epigenetic approaches to frame biological markers of
      musicianship in the context of interactions between genetic and experience
      related factors. 

PMID- 24137143
TI  - Benefits and detriments of unilateral cochlear implant use on bilateral auditory
      development in children who are deaf.
AB  - We have explored both the benefits and detriments of providing electrical input
      through a cochlear implant in one ear to the auditory system of young children. A
      cochlear implant delivers electrical pulses to stimulate the auditory nerve,
      providing children who are deaf with access to sound. The goals of implantation
      are to restrict reorganization of the deprived immature auditory brain and
      promote development of hearing and spoken language. It is clear that limiting the
      duration of deprivation is a key factor. Additional considerations are the onset,
      etiology, and use of residual hearing as each of these can have unique effects on
      auditory development in the pre-implant period. New findings show that many
      children receiving unilateral cochlear implants are developing mature-like
      brainstem and thalamo-cortical responses to sound with long term use despite
      these sources of variability; however, there remain considerable abnormalities in
      cortical function. The most apparent, determined by implanting the other ear and
      measuring responses to acute stimulation, is a loss of normal cortical response
      from the deprived ear. Recent data reveal that this can be avoided in children by
      early implantation of both ears simultaneously or with limited delay. We conclude
      that auditory development requires input early in development and from both ears.

PMID- 24137146
TI  - Modeling effects of intrinsic and extrinsic rewards on the competition between
      striatal learning systems.
AB  - A common assumption in psychology, economics, and other fields holds that higher
      performance will result if extrinsic rewards (such as money) are offered as an
      incentive. While this principle seems to work well for tasks that require the
      execution of the same sequence of steps over and over, with little uncertainty
      about the process, in other cases, especially where creative problem solving is
      required due to the difficulty in finding the optimal sequence of actions,
      external rewards can actually be detrimental to task performance. Furthermore,
      they have the potential to undermine intrinsic motivation to do an otherwise
      interesting activity. In this work, we extend a computational model of the
      dorsomedial and dorsolateral striatal reinforcement learning systems to account
      for the effects of extrinsic and intrinsic rewards. The model assumes that the
      brain employs both a goal-directed and a habitual learning system, and
      competition between both is based on the trade-off between the cost of the
      reasoning process and value of information. The goal-directed system elicits
      internal rewards when its models of the environment improve, while the habitual
      system, being model-free, does not. Our results account for the phenomena that
      initial extrinsic reward leads to reduced activity after extinction compared to
      the case without any initial extrinsic rewards, and that performance in complex
      task settings drops when higher external rewards are promised. We also test the
      hypothesis that external rewards bias the competition in favor of the
      computationally efficient, but cruder and less flexible habitual system, which
      can negatively influence intrinsic motivation and task performance in the class
      of tasks we consider. 

PMID- 24137144
TI  - Controversies over the mechanisms underlying the crucial role of the left fronto
      parietal areas in the representation of tools.
AB  - Anatomo-clinical and neuroimaging data show that the left fronto-parietal areas
      play an important role in representing tools. As manipulation is an important
      source of knowledge about tools, it has been assumed that motor activity explains
      the link between tool knowledge and the left fronto-parietal areas. However,
      controversies exist over the exact mechanisms underlying this relationship.
      According to a strong version of the "embodied cognition theory," activation of a
      tool concept necessarily involves re-enactment of the corresponding kind of
      action. Impairment of the ability to use tools should, therefore, lead to
      impairment of tool knowledge. Both the "domains of knowledge hypothesis" and the
      "sensory-motor model of conceptual knowledge" refute the strong version of the
      "embodied cognition hypothesis" but acknowledge that manipulation and other
      action schemata play an important role in our knowledge of tools. The basic
      difference between these two models is that the former is based on an innate
      model and the latter holds that the brain's organization of categories is
      experience dependent. Data supporting and arguing against each of these models
      are briefly reviewed. In particular, the following lines of research, which argue
      against the innate nature of the brain's categorical organization, are discussed:
      (1) the observation that in patients with category-specific disorders the
      semantic impairment does not respect the boundaries between biological entities
      and artifact items; (2) data showing that experience-driven neuroplasticity in
      musicians is not confined to alterations of perceptual and motor maps but also
      leads to the establishment of higher-level semantic representations for musical
      instruments; (3) results of experiments using previously unfamiliar materials
      showing that the history of our sensory-motor experience with an object
      significantly affects its neural representation. 

PMID- 24137147
TI  - Can mind-wandering be timeless? Atemporal focus and aging in mind-wandering
      paradigms.
AB  - Recent research has examined how often mind-wandering occurs about past vs.
      future events. However, mind-wandering may also be atemporal, although previous
      investigations of this possibility have not yielded consistent results. Indeed,
      it is unclear what proportion of mind-wandering is atemporal, and also how an
      atemporal response option would affect the future-oriented bias often reported
      during low-demand tasks used to measure mind-wandering. The present study
      examined self-reported (Experiment 1) and probe-caught (Experiment 2) mind
      wandering using the low-demand Sustained Attention to Response Task (SART) in
      younger (18-30) and older (50-73) adults in an experimental paradigm developed to
      measure mind-wandering using Amazon's Mechanical Turk (Mturk). Across self
      reported and probe-caught mind-wandering, the atemporal response option was used
      at least as frequently as past or future mind-wandering options. Although older
      adults reported far fewer mind-wandering events, they showed a very similar
      temporal pattern to younger adults. Most importantly, inclusion of the atemporal
      report option affected performance on the SART and selectively eliminated the
      prospective bias in self-reported mind-wandering, but not in probe-caught mind
      wandering. These results suggest that both young and older participants are often
      not thinking of past or future events when mind-wandering, but are thinking of
      events that cannot easily be categorized as either. 

PMID- 24137145
TI  - The beneficial effects of meditation: contribution of the anterior cingulate and
      locus coeruleus.
AB  - During functional magnetic resonance imaging studies of meditation the cortical
      salience detecting and executive networks become active during "awareness of mind
      wandering," "shifting," and "sustained attention." The anterior cingulate (AC) is
      activated during "awareness of mind wandering." The AC modulates both the
      peripheral sympathetic nervous system (SNS) and the central locus coeruleus (LC)
      norepinephrine systems, which form the principal neuromodulatory system,
      regulating in multiple ways both neuronal and non-neuronal cells to maximize
      adaptation in changing environments. The LC is the primary source of central
      norepinephrine (C-NE) and nearly the exclusive source of cortical norepinephrine.
      Normally activated by novel or salient stimuli, the AC initially inhibits the SNS
      reflexively, lowering peripheral norepinephrine and activates the LC, increasing
      C-NE. Moderate levels of C-NE enhance working memory through alpha 2 adrenergic
      receptors, while higher levels of C-NE, acting on alpha 1 and beta receptors,
      enhance other executive network functions such as the stopping of ongoing
      behavior, attentional set-shifting, and sustained attention. The actions of the
      AC on both the central and peripheral noradrenergic systems are implicated in the
      beneficial effects of meditation. This paper will explore some of the known
      functions and interrelationships of the AC, SNS, and LC with respect to their
      possible relevance to meditation. 

PMID- 24137149
TI  - Are implicit motives revealed in mere words? Testing the marker-word hypothesis
      with computer-based text analysis.
AB  - Traditionally, implicit motives (i.e., non-conscious preferences for specific
      classes of incentives) are assessed through semantic coding of imaginative
      stories. The present research tested the marker-word hypothesis, which states
      that implicit motives are reflected in the frequencies of specific words. Using
      Linguistic Inquiry and Word Count (LIWC; Pennebaker et al., 2001), Study 1
      identified word categories that converged with a content-coding measure of the
      implicit motives for power, achievement, and affiliation in picture stories
      collected in German and US student samples, showed discriminant validity with
      self-reported motives, and predicted well-validated criteria of implicit motives
      (gender difference for the affiliation motive; in interaction with personal-goal
      progress: emotional well-being). Study 2 demonstrated LIWC-based motive scores'
      causal validity by documenting their sensitivity to motive arousal. 

PMID- 24137148
TI  - Olfactory consciousness and gamma oscillation couplings across the olfactory
      bulb, olfactory cortex, and orbitofrontal cortex.
AB  - The orbitofrontal cortex receives multi-modality sensory inputs, including
      olfactory input, and is thought to be involved in conscious perception of the
      olfactory image of objects. Generation of olfactory consciousness may require
      neuronal circuit mechanisms for the "binding" of distributed neuronal activities,
      with each constituent neuron representing a specific component of an olfactory
      percept. The shortest neuronal pathway for odor signals to reach the
      orbitofrontal cortex is olfactory sensory neuron-olfactory bulb-olfactory cortex
      orbitofrontal cortex, but other pathways exist, including transthalamic pathways.
      Here, we review studies on the structural organization and functional properties
      of the shortest pathway, and propose a model of neuronal circuit mechanisms
      underlying the temporal bindings of distributed neuronal activities in the
      olfactory cortex. We describe a hypothesis that suggests functional roles of
      gamma oscillations in the bindings. This hypothesis proposes that two types of
      projection neurons in the olfactory bulb, tufted cells and mitral cells, play
      distinct functional roles in bindings at neuronal circuits in the olfactory
      cortex: tufted cells provide specificity-projecting circuits which send odor
      information with early-onset fast gamma synchronization, while mitral cells give
      rise to dispersedly-projecting feed-forward binding circuits which transmit the
      response synchronization timing with later-onset slow gamma synchronization. This
      hypothesis also suggests a sequence of bindings in the olfactory cortex: a small
      scale binding by the early-phase fast gamma synchrony of tufted cell inputs
      followed by a larger-scale binding due to the later-onset slow gamma synchrony of
      mitral cell inputs. We discuss that behavioral state, including wakefulness and
      sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory
      cortex, and orbitofrontal cortex. 

PMID- 24137151
TI  - Accelerated long-term forgetting in aging and intra-sleep awakenings.
AB  - The architecture of sleep and the functional neuroanatomical networks subtending
      memory consolidation processes are both modified with aging, possibly leading to
      accelerated forgetting in long-term memory. We investigated associative learning
      and declarative memory consolidation processes in 16 young (18-30 years) and 16
      older (65-75 years) healthy adults. Performance was tested using a cued recall
      procedure at the end of learning (immediate recall), and 30 min and 7 days later.
      A delayed recognition test was also administered on day 7. Daily sleep diaries
      were completed during the entire experiment. Results revealed a similar
      percentage of correct responses at immediate and 30-min recall in young and older
      participants. However, recall was significantly decreased 7 days later, with an
      increased forgetting in older participants. Additionally, intra-sleep awakenings
      were more frequent in older participants than young adults during the seven
      nights, and were negatively correlated with delayed recall performance on day 7
      in the older group. Altogether, our results suggest a decline in verbal
      declarative memory consolidation processes with aging, eventually leading to
      accelerated long-term forgetting indicating that increased sleep fragmentation
      due to more frequent intra-sleep awakenings in older participants contribute to
      the reported age-related decline in long-term memory retrieval. Our results
      highlight the sensitivity of long-term forgetting measures to evidence
      consolidation deficits in healthy aging. 

PMID- 24137150
TI  - Quantitative meta-analysis of fMRI and PET studies reveals consistent activation
      in fronto-striatal-parietal regions and cerebellum during antisaccades and
      prosaccades.
AB  - The antisaccade task is a classic task of oculomotor control that requires
      participants to inhibit a saccade to a target and instead make a voluntary
      saccade to the mirror opposite location. By comparison, the prosaccade task
      requires participants to make a visually-guided saccade to the target. These
      tasks have been studied extensively using behavioral oculomotor,
      electrophysiological, and neuroimaging in both non-human primates and humans. In
      humans, the antisaccade task is under active investigation as a potential
      endophenotype or biomarker for multiple psychiatric and neurological disorders. A
      large and growing body of literature has used functional magnetic resonance
      imaging (fMRI) and positron emission tomography (PET) to study the neural
      correlates of the antisaccade and prosaccade tasks. We present a quantitative
      meta-analysis of all published voxel-wise fMRI and PET studies (18) of the
      antisaccade task and show that consistent activation for antisaccades and
      prosaccades is obtained in a fronto-subcortical-parietal network encompassing
      frontal and supplementary eye fields (SEFs), thalamus, striatum, and
      intraparietal cortex. This network is strongly linked to oculomotor control and
      was activated to a greater extent for antisaccade than prosaccade trials.
      Antisaccade but not prosaccade trials additionally activated dorsolateral and
      ventrolateral prefrontal cortices. We also found that a number of additional
      regions not classically linked to oculomotor control were activated to a greater
      extent for antisaccade vs. prosaccade trials; these regions are often reported in
      antisaccade studies but rarely commented upon. While the number of studies
      eligible to be included in this meta-analysis was small, the results of this
      systematic review reveal that antisaccade and prosaccade trials consistently
      activate a distributed network of regions both within and outside the classic
      definition of the oculomotor network. 

PMID- 24137152
TI  - Synaesthesia and sexuality: the influence of synaesthetic perceptions on sexual
      experience.
AB  - INTRODUCTION: Synaesthesia is a phenomenon in which a certain stimulus induces a
      concurrent sensory perception; it has an estimated prevalence of 4%. Sexual
      arousal as an inducer for synaesthetic perceptions is rarely mentioned in the
      literature but can be found sometimes in case reports about subjective orgasmic
      experiences. AIMS: To examine whether synaesthetic perceptions during sexual
      intercourse have an impact on the sexual experience and the extent of sexual
      trance compared to non-synaesthetes. METHODS: In total, 19 synaesthetes with
      sexual forms of synaesthesia (17 female; 2 male) were included as well as
      corresponding control data of 36 non-synaesthetic subjects (n = 55). Two
      questionnaires were used to assess relevant aspects of sexual function and
      dysfunction (a German adaption of the Brief Index of Sexual Functioning, KFSP) as
      well as the occurrence and extent of sexual trance (German version of the Altered
      States of Consciousness Questionnaire, OAVAV). Additionally qualitative
      interviews were conducted in some subjects to further explore the nature of
      sexual experiences in synaesthetes. MAIN OUTCOME MEASURES: Sexual experience and
      extent of sexual trance during intercourse. RESULTS: Synaesthetes depicted
      significantly better overall sexual function on the KFSP with increased scores
      for the subscale "sexual appetence" but coevally significant lower subscale
      scores for "sexual satisfaction." Sexual dysfunction was not detected in this
      sample. Synaesthetes depicted significantly higher levels of the subscales
      "oceanic boundlessness" and "visionary restructuralization" than controls using
      the OAVAV. Qualitative interviews revealed varying synaesthetic perceptions
      during the different states of arousal. Furthermore, synaesthetes reported an
      unsatisfactory feeling of isolation caused by the idiosyncratic perceptions.
      CONCLUSIONS: Synaesthetes with sexual forms of synaesthesia seem to experience a
      deeper state of sexual trance without, however, enhanced satisfaction during
      sexual intercourse.

PMID- 24137154
TI  - Glioblastoma mimicking an arteriovenous malformation.
AB  - Abnormal cerebral vasculature can be a manifestation of a vascular malformation
      or a neoplastic process. We report the case of a patient with angiography
      negative subarachnoid hemorrhage (SAH) who re-presented 3 years later with a
      large intraparenchymal hemorrhage. Although imaging following the
      intraparenchymal hemorrhage was suggestive of arteriovenous malformation, the
      patient was ultimately found to have an extensive glioblastoma associated with
      abnormal tumor vasculature. The case emphasizes the need for magnetic resonance
      imaging to investigate angiography-negative SAH in suspicious cases to rule out
      occult etiologies, such as neoplasm. We also discuss diagnostic pitfalls when
      brain tumors are associated with hemorrhage and abnormal vasculature. 

PMID- 24137153
TI  - Sleep-dependent synaptic down-selection (I): modeling the benefits of sleep on
      memory consolidation and integration.
AB  - Sleep can favor the consolidation of both procedural and declarative memories,
      promote gist extraction, help the integration of new with old memories, and
      desaturate the ability to learn. It is often assumed that such beneficial effects
      are due to the reactivation of neural circuits in sleep to further strengthen the
      synapses modified during wake or transfer memories to different parts of the
      brain. A different possibility is that sleep may benefit memory not by further
      strengthening synapses, but rather by renormalizing synaptic strength to restore
      cellular homeostasis after net synaptic potentiation in wake. In this way, the
      sleep-dependent reactivation of neural circuits could result in the competitive
      down-selection of synapses that are activated infrequently and fit less well with
      the overall organization of memories. By using computer simulations, we show here
      that synaptic down-selection is in principle sufficient to explain the beneficial
      effects of sleep on the consolidation of procedural and declarative memories, on
      gist extraction, and on the integration of new with old memories, thereby
      addressing the plasticity-stability dilemma. 

PMID- 24137155
TI  - Predicting early awakening from coma after intracerebral hemorrhage.
AB  - INTRODUCTION: Given the high morbidity and mortality associated with
      intracerebral hemorrhage (ICH), family members, and healthcare providers base
      early supportive management decisions, at least in part, on expected prognosis.
      In the comatose patient with ICH, this short-term prognosis is most overtly
      characterized by regaining of consciousness. DESIGN: A retrospective consecutive
      cohort of 51 patients admitted to a neuroICU with ICH and admission Glasgow Coma
      Scale score <=8 was identified. Logistic regression was performed to assess the
      association of baseline characteristics and treatment parameters associated with
      awakening. RESULTS: Awakening from coma was observed in 53% of ICH patients: 83%
      with an initial GCS score of 7-8, 43% with an initial score of 5-6, and 20% with
      an initial score of 3-4. Awakening from coma in the cohort of 27 patients who
      regained consciousness occurred in 59% of patients by day 2, 89% by day 7, and
      96% by day 9. In multivariable analysis, only higher admission GCS score was
      associated with a greater likelihood of awakening from coma [OR 4.9 (95% CI 1.9
      13) per two-point category, p = 0.001]. DNR status during the first 24 h was not
      associated with awakening but was at later time points. CONCLUSION: GCS score is
      the predominant initial predictor of early awakening in patients who present in
      coma after ICH. Patients who regained consciousness typically did so within the
      first 9 days of hospital admission.

PMID- 24137157
TI  - Glutamine synthetase as an astrocytic marker: its cell type and vesicle
      localization.

PMID- 24137156
TI  - GnRH-Induced Ca(2+) Signaling Patterns and Gonadotropin Secretion in Pituitary
      Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary
      Physiological Demands.
AB  - PITUITARY GONADOTROPHS ARE A SMALL FRACTION OF THE ANTERIOR PITUITARY POPULATION,
      YET THEY SYNTHESIZE GONADOTROPINS: luteinizing (LH) and follicle-stimulating
      (FSH), essential for gametogenesis and steroidogenesis. LH is secreted via a
      regulated pathway while FSH release is mostly constitutive and controlled by
      synthesis. Although gonadotrophs fire action potentials spontaneously, the
      intracellular Ca(2+) rises produced do not influence secretion, which is mainly
      driven by Gonadotropin-Releasing Hormone (GnRH), a decapeptide synthesized in the
      hypothalamus and released in a pulsatile manner into the hypophyseal portal
      circulation. GnRH binding to G-protein-coupled receptors triggers Ca(2+)
      mobilization from InsP3-sensitive intracellular pools, generating the global
      Ca(2+) elevations necessary for secretion. Ca(2+) signaling responses to
      increasing (GnRH) vary in stereotyped fashion from subthreshold to baseline
      spiking (oscillatory), to biphasic (spike-oscillatory or spike-plateau). This
      progression varies somewhat in gonadotrophs from different species and biological
      preparations. Both baseline spiking and biphasic GnRH-induced Ca(2+) signals
      control LH/FSH synthesis and exocytosis. Estradiol and testosterone regulate
      gonadotropin secretion through feedback mechanisms, while FSH synthesis and
      release are influenced by activin, inhibin, and follistatin. Adaptation to
      physiological events like the estrous cycle, involves changes in GnRH sensitivity
      and LH/FSH synthesis: in proestrus, estradiol feedback regulation abruptly
      changes from negative to positive, causing the pre-ovulatory LH surge. Similarly,
      when testosterone levels drop after orquiectomy the lack of negative feedback on
      pituitary and hypothalamus boosts both GnRH and LH secretion, gonadotrophs GnRH
      sensitivity increases, and Ca(2+) signaling patterns change. In addition,
      gonadotrophs proliferate and grow. These plastic changes denote a more vigorous
      functional adaptation in response to an extraordinary functional demand. 

PMID- 24137158
TI  - Comparison of Nephrolithiasis Prevalence in Two Bottlenose Dolphin (Tursiops
      truncatus) Populations.
AB  - In humans, ammonium urate (AU) nephrolithiasis is rare in the Western hemisphere
      and more common in Japan and developing countries. Among a variety of risk
      factors, insulin resistance has been associated with urate nephrolithiasis in
      people. Bottlenose dolphins (Tursiops truncatus) are susceptible to AU
      nephrolithiasis, and it is believed that some populations are more likely to
      develop nephrolithiasis compared to others. In an effort to better understand
      population-based risk factors for AU nephrolithiasis in dolphins and their
      comparative value to humans, sonographic evaluation was performed on dolphins
      from a managed collection in San Diego Bay, CA (n = 40) and dolphins from a free
      ranging, nearshore population in Sarasota Bay, FL (n = 39) to look for evidence
      of nephrolithiasis. While 14 (35%) of San Diego Bay dolphins evaluated for the
      study had sonographic evidence of nephrolithiasis, none of the Sarasota Bay
      dolphins had evidence of disease. Presence or absence of stones was confirmed by
      computed tomography in a subset of the San Diego collection (n = 10; four
      dolphins with stones, six without stones). Age was identified as a risk factor,
      as dolphins with stones in the San Diego collection were significantly older than
      dolphins without stones (25.4 vs. 19.1 years, respectively; P = 0.04).
      Additionally, San Diego dolphins included in the study were significantly older
      than Sarasota Bay dolphins (21.3 vs. 13.8 years, respectively; P = 0.008). In
      addition to the previously reported risk factors of hypocitraturia and
      hyperinsulinemia in bottlenose dolphins, other potential factors include
      geographic location, managed vs. free-ranging status, prey species, and feeding
      schedules. 

PMID- 24137159
TI  - Life cycle of phytoreoviruses visualized by electron microscopy and tomography.
AB  - Rice dwarf virus and Rice gall dwarf virus, members of the genus Phytoreovirus in
      the family Reoviridae,are known as agents of rice disease, because their spread
      results in substantial economic damage in many Asian countries. These viruses are
      transmitted via insect vectors, and they multiply both in the plants and in the
      insect vectors. Structural information about the viruses and their interactions
      with cellular components in the life cycle are essential for understanding viral
      infection and replication mechanisms. The life cycle of the viruses involves
      various cellular events such as cell entry, synthesis of viral genome and
      proteins, assembly of viral components, viral egress from infected cells, and
      intra- and intercellular transports. This review focuses on the major events
      underlying the life cycle of phytoreoviruses, which has been visualized by
      various electron microscopy (EM) imaging techniques, including cryo-electron
      microscopy and tomography, and demonstrates the advantage of the advanced EM
      imaging techniques to investigate the viral infection and replication mechanisms.

PMID- 24137160
TI  - Intestinal epithelium and autophagy: partners in gut homeostasis.
AB  - One of the most significant challenges of cell biology is to understand how each
      type of cell copes with its specific workload without suffering damage. Among the
      most intriguing questions concerns intestinal epithelial cells in mammals; these
      cells act as a barrier between the internally protected region and the external
      environment that is exposed constantly to food and microbes. A major process
      involved in the processing of microbes is autophagy. In the intestine, through
      multiple, complex signaling pathways, autophagy including macroautophagy and
      xenophagy is pivotal in mounting appropriate intestinal immune responses and anti
      microbial protection. Dysfunctional autophagy mechanism leads to chronic
      intestinal inflammation, such as inflammatory bowel disease (IBD). Studies
      involving a number of in vitro and in vivo mouse models in addition to human
      clinical studies have revealed a detailed role for autophagy in the generation of
      chronic intestinal inflammation. A number of genome-wide association studies
      identified roles for numerous autophagy genes in IBD, especially in Crohn's
      disease. In this review, we will explore in detail the latest research linking
      autophagy to intestinal homeostasis and how alterations in autophagy pathways
      lead to intestinal inflammation. 

PMID- 24137161
TI  - Regulatory T cell subsets in filarial infection and their function.
AB  - Filarial infections in humans are chronic infections that cause significant
      morbidity. The chronic nature of these infections with continuous antigen release
      is associated with a parasite-specific T cell hypo-responsiveness that may over
      time also affect the immune responses to bystander antigens. Previous studies
      have shown the filarial parasite antigen-specific T cells hypo-responsiveness is
      mediated by regulatory cytokines - IL-10 and TGF-beta in particular. Recent
      studies have suggested that the modulated/regulated T cell responses associated
      with patent filarial infection may reflect an expansion of regulatory T cells
      (Tregs) that include both Tregs induced in peripheral circulation or pTregs and
      the thymus-derived Tregs or tTregs. Although much is known about the phenotype of
      these regulatory populations, the mechanisms underlying their expansion and their
      mode of action in filarial and other infections remain unclear. Nevertheless
      there are data to suggest that while many of these regulatory cells are activated
      in an antigen-specific manner the ensuing effectors of this activation are
      relatively non-specific and may affect a broad range of immune cells. This review
      will focus on the subsets and function of regulatory T cells in filarial
      infection. 

PMID- 24137162
TI  - CD90(+) Stromal Cells are Non-Professional Innate Immune Effectors of the Human
      Colonic Mucosa.
AB  - Immune responses at the intestinal mucosa must allow for host protection whilst
      simultaneously avoiding inappropriate inflammation. Although much work has
      focused on the innate immune functionality of hematopoietic immune cells, non
      hematopoietic cell populations - including epithelial and stromal cells - are now
      recognized as playing a key role in innate defense at this site. In this study we
      examined the innate immune capacity of primary human intestinal stromal cells
      (iSCs). CD90(+) iSCs isolated from human colonic mucosa expressed a wide array of
      innate immune receptors and functionally responded to stimulation with bacterial
      ligands. iSCs also sensed infection with live Salmonella typhimurium, rapidly
      expressing IL-1 family cytokines via a RIPK2/p38MAPK-dependent signaling process.
      In addition to responding to innate immune triggers, primary iSCs exhibited a
      capacity for bacterial uptake, phagocytosis, and antigen processing, although to
      a lesser extent than professional APCs. Thus CD90(+) iSCs represent an abundant
      population of "non-professional" innate immune effector cells of the human
      colonic mucosa and likely play an important adjunctive role in host defense and
      immune regulation at this site. 

PMID- 24137164
TI  - The Subtelomeric khipu Satellite Repeat from Phaseolus vulgaris: Lessons Learned
      from the Genome Analysis of the Andean Genotype G19833.
AB  - Subtelomeric regions in eukaryotic organisms are known for harboring species
      specific tandemly repeated satellite sequences. However, studies on the molecular
      organization and evolution of subtelomeric repeats are scarce, especially in
      plants. Khipu is a satellite DNA of 528-bp repeat unit, specific of the Phaseolus
      genus, with a subtelomeric distribution in common bean, P. vulgaris. To
      investigate the genomic organization and the evolution of khipu, we performed
      genome-wide analysis on the complete genome sequence of the common bean genotype
      G19833. We identified 2,460 khipu units located at most distal ends of the
      sequenced regions. Khipu units are arranged in discrete blocks of 2-55 copies and
      are heterogeneously distributed among the different chromosome ends of G19833
      (from 0 to 555 khipus units per chromosome arm). Phylogenetically related khipu
      units are spread between numerous chromosome ends, suggesting frequent exchanges
      between non-homologous subtelomeres. However, most subclades contain numerous
      khipu units from only one or few chromosome ends indicating that local
      duplication is also driving khipu expansion. Unexpectedly, we also identified 81
      khipu units located at centromeres. All the centromeric khipu units belong to a
      single divergent clade also comprised of a few units from several subtelomeres,
      suggesting that a few sequence exchanges between centromeres and subtelomeres
      took place in the common bean genome. The divergence and low copy number of these
      centromeric units from the subtelomeric units could explain why they were not
      detected by FISH (Fluorescence in situ Hybridization) although it can not be
      excluded that these centromeric units may have resulted from errors in the
      pseudomolecule assembly. Altogether our data highlight extensive sequence
      exchanges in subtelomeres between non-homologous chromosomes in common bean and
      confirm that subtelomeres represent one of the most dynamic and rapidly evolving
      regions in eukaryotic genomes. 

PMID- 24137167
TI  - Vascular anatomy of kiwi fruit and its implications for the origin of carpels.
AB  - Kiwi fruit is of great agricultural, botanical, and economic interest. The flower
      of kiwi fruit has axile placentation, which is typical for Actinidiaceae. Axile
      placentation is thought derived through fusion of conduplicate carpels with
      marginal placentation according to the traditional doctrine. Recent progress in
      angiosperm systematics has refuted this traditional doctrine and placed ANITA
      clade rather than Magnoliaceae as the basalmost clade. However, the former
      traditional doctrine stays in the classrooms as the only teachable theory for the
      origin of carpels. To test the validity of this doctrine, we performed anatomical
      study on kiwi fruit. Our study indicates that the placenta has a vascular system
      independent of that of the ovary wall, the ovules/seeds are attached to the
      placenta that is a continuation of floral axis enclosed by the lateral appendages
      that constitute the ovary wall, and there are some amphicribral bundles in the
      center of placenta and numerous amphicribral bundles supplying ovules/seeds in
      kiwi fruit. The amphicribral vascular bundles supplying the ovules/seeds are
      comparable to those usually seen in branches, but not comparable to those seen in
      leaves or their derivatives. This comparison indicates that the placenta in kiwi
      fruit cannot be derived from the fusion of collateral ventral bundles of
      conduplicate carpels, as suggested by traditional doctrine. Instead the vascular
      organization in placenta of kiwi suggests that the placenta is a shoot apex
      bearing ovules/seeds laterally. This conclusion is in line with the recently
      raised Unifying Theory, in which the placenta is taken as an ovule-bearing branch
      independent of the ovary wall (carpel in strict sense). Similar vascular
      organization in placenta has been seen in numerous isolated taxa besides kiwi
      fruit. Therefore whether such a pattern is applicable for other angiosperms is an
      interesting question awaiting answering. 

PMID- 24137166
TI  - Overexpression of plastidial thioredoxins f and m differentially alters
      photosynthetic activity and response to oxidative stress in tobacco plants.
AB  - Plants display a remarkable diversity of thioredoxins (Trxs), reductases
      controlling the thiol redox status of proteins. The physiological function of
      many of them remains elusive, particularly for plastidial Trxs f and m, which are
      presumed based on biochemical data to regulate photosynthetic reactions and
      carbon metabolism. Recent reports revealed that Trxs f and m participate in vivo
      in the control of starch metabolism and cyclic photosynthetic electron transfer
      around photosystem I, respectively. To further delineate their in planta
      function, we compared the photosynthetic characteristics, the level and/or
      activity of various Trx targets and the responses to oxidative stress in
      transplastomic tobacco plants overexpressing either Trx f or Trx m. We found that
      plants overexpressing Trx m specifically exhibit altered growth, reduced
      chlorophyll content, impaired photosynthetic linear electron transfer and
      decreased pools of glutathione and ascorbate. In both transplastomic lines,
      activities of two enzymes involved in carbon metabolism, NADP-malate
      dehydrogenase and NADP-glyceraldehyde-3-phosphate dehydrogenase are markedly and
      similarly altered. In contrast, plants overexpressing Trx m specifically display
      increased capacity for methionine sulfoxide reductases, enzymes repairing damaged
      proteins by regenerating methionine from oxidized methionine. Finally, we also
      observed that transplastomic plants exhibit distinct responses when exposed to
      oxidative stress conditions generated by methyl viologen or exposure to high
      light combined with low temperature, the plants overexpressing Trx m being
      notably more tolerant than Wt and those overexpressing Trx f. Altogether, these
      data indicate that Trxs f and m fulfill distinct physiological functions. They
      prompt us to propose that the m type is involved in key processes linking
      photosynthetic activity, redox homeostasis and antioxidant mechanisms in the
      chloroplast. 

PMID- 24137165
TI  - Analyzing spatial patterns linked to the ecology of herbivores and their natural
      enemies in the soil.
AB  - Modern agricultural systems can benefit from the application of concepts and
      models from applied ecology. When understood, multitrophic interactions among
      plants, pests, diseases and their natural enemies can be exploited to increase
      crop production and reduce undesirable environmental impacts. Although the
      understanding of subterranean ecology is rudimentary compared to the perspective
      aboveground, technologies today vastly reduce traditional obstacles to studying
      cryptic communities. Here we emphasize advantages to integrating as much as
      possible the use of these methods in order to leverage the information gained
      from studying communities of soil organisms. PCR-based approaches to identify and
      quantify species (real time qPCR and next generation sequencing) greatly expand
      the ability to investigate food web interactions because there is less need for
      wide taxonomic expertise within research programs. Improved methods to capture
      and measure volatiles in the soil atmosphere in situ make it possible to detect
      and study chemical cues that are critical to communication across trophic levels.
      The application of SADIE to directly assess rather than infer spatial patterns in
      belowground agroecosystems has improved the ability to characterize relationships
      between organisms in space and time. We review selected methodology and use of
      these tools and describe some of the ways they were integrated to study soil food
      webs in Florida citrus orchards with the goal of developing new biocontrol
      approaches. 

PMID- 24137168
TI  - Disentangling who is who during rhizosphere acidification in root interactions:
      combining fluorescence with optode techniques.
AB  - Plant-soil interactions can strongly influence root growth in plants. There is
      now increasing evidence that root-root interactions can also influence root
      growth, affecting architecture and root traits such as lateral root formation.
      Both when species grow alone or in interaction with others, root systems are in
      turn affected by as well as affect rhizosphere pH. Changes in soil pH have knock
      on effects on nutrient availability. A limitation until recently has been the
      inability to assign species identity to different roots in soil. Combining the
      planar optode technique with fluorescent plants enables us to distinguish between
      plant species grown in natural soil and in parallel study pH dynamics in a non
      invasive way at the same region of interest (ROI). We measured pH in the
      rhizosphere of maize and bean in rhizotrons in a climate chamber, with ROIs on
      roots in proximity to the roots of the other species as well as not-close to the
      other species. We found clear dynamic changes of pH over time and differences
      between the two species in rhizosphere acidification. Interestingly, when roots
      of the two species were interacting, the degree of acidification or alkalization
      compared to bulk soil was less strong then when roots were not growing in the
      vicinity of the other species. This cutting-edge approach can help provide a
      better understanding of plant-plant and plant-soil interactions. 

PMID- 24137163
TI  - Functions of NOD-Like Receptors in Human Diseases.
AB  - Nucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are
      highly conserved cytosolic pattern recognition receptors that perform critical
      functions in surveying the intracellular environment for the presence of
      infection, noxious substances, and metabolic perturbations. Sensing of these
      danger signals by NLRs leads to their oligomerization into large macromolecular
      scaffolds and the rapid deployment of effector signaling cascades to restore
      homeostasis. While some NLRs operate by recruiting and activating inflammatory
      caspases into inflammasomes, others trigger inflammation via alternative routes
      including the nuclear factor-kappaB, mitogen-activated protein kinase, and
      regulatory factor pathways. The critical role of NLRs in development and
      physiology is demonstrated by their clear implications in human diseases.
      Mutations in the genes encoding NLRP3 or NLRP12 lead to hereditary periodic fever
      syndromes, while mutations in CARD15 that encodes NOD2 are linked to Crohn's
      disease or Blau's syndrome. Genome-wide association studies (GWASs) have
      identified a number of risk alleles encompassing NLR genes in a host of diseases
      including allergic rhinitis, multiple sclerosis, inflammatory bowel disease,
      asthma, multi-bacillary leprosy, vitiligo, early-onset menopause, and bone
      density loss in elderly women. Animal models have allowed the characterization of
      underlying effector mechanisms in a number of cases. In this review, we highlight
      the functions of NLRs in health and disease and discuss how the characterization
      of their molecular mechanisms provides new insights into therapeutic strategies
      for the management of inflammatory pathologies. 

PMID- 24137169
TI  - The current status of the elemental defense hypothesis in relation to pathogens.
AB  - Metal hyperaccumulating plants are able to accumulate exceptionally high
      concentrations of metals, such as zinc, nickel, or cadmium, in their aerial
      tissues. These metals reach concentrations that would be toxic to most other
      plant species. This trait has evolved multiple times independently in the plant
      kingdom. Recent studies have provided new insight into the ecological and
      evolutionary significance of this trait, by showing that some metal
      hyperaccumulating plants can use high concentrations of accumulated metals to
      defend themselves against attack by pathogenic microorganisms and herbivores.
      Here, we review the evidence that metal hyperaccumulation acts as a defensive
      trait in plants, with particular emphasis on plant-pathogen interactions. We
      discuss the mechanisms by which defense against pathogens might have driven the
      evolution of metal hyperaccumulation, including the interaction of this trait
      with other forms of defense. In particular, we consider how physiological
      adaptations and fitness costs associated with metal hyperaccumulation could have
      resulted in trade-offs between metal hyperaccumulation and other defenses.
      Drawing on current understanding of the population ecology of metal
      hyperaccumulator plants, we consider the conditions that might have been
      necessary for metal hyperaccumulation to be selected as a defensive trait, and
      discuss the likelihood that these were fulfilled. Based on these conditions, we
      propose a possible scenario for the evolution of metal hyperaccumulation, in
      which selective pressure for resistance to pathogens or herbivores, combined with
      gene flow from non-metallicolous populations, increases the likelihood that the
      metal hyperaccumulating trait becomes established in plant populations. 

PMID- 24137170
TI  - Signaling of double strand breaks and deprotected telomeres in Arabidopsis.
AB  - Failure to repair DNA double strand breaks (DSB) can lead to chromosomal
      rearrangements and eventually to cancer or cell death. Radiation and
      environmental pollutants induce DSB and this is of particular relevance to plants
      due to their sessile life style. DSB also occur naturally in cells during DNA
      replication and programmed induction of DSB initiates the meiotic recombination
      essential for gametogenesis in most eukaryotes. The linear nature of most
      eukaryotic chromosomes means that each chromosome has two "broken" ends.
      Chromosome ends, or telomeres, are protected by nucleoprotein caps which avoid
      their recognition as DSB by the cellular DNA repair machinery. Deprotected
      telomeres are recognized as DSB and become substrates for recombination leading
      to chromosome fusions, the "bridge-breakage-fusion" cycle, genome rearrangements
      and cell death. The importance of repair of DSB and the severity of the
      consequences of their misrepair have led to the presence of multiple, robust
      mechanisms for their detection and repair. After a brief overview of DSB repair
      pathways to set the context, we present here an update of current understanding
      of the detection and signaling of DSB in the plant, Arabidopsis thaliana. 

PMID- 24137171
TI  - Analysis of the role of Arabidopsis class I TCP genes AtTCP7, AtTCP8, AtTCP22,
      and AtTCP23 in leaf development.
AB  - TCP family of plant-specific transcription factors regulates plant form through
      control of cell proliferation and differentiation. This gene family is comprised
      of two groups, class I and class II. While the role of class II TCP genes in
      plant development is well known, data about the function of some class I TCP
      genes is lacking. We studied a group of phylogenetically related class I TCP
      genes: AtTCP7, AtTCP8, AtTCP22, and AtTCP23. The similar expression pattern in
      young growing leaves found for this group suggests similarity in gene function.
      Gene redundancy is characteristic in this group, as also seen in the class II TCP
      genes. We generated a pentuple mutant tcp8 tcp15 tcp21 tcp22 tcp23 and show that
      loss of function of these genes results in changes in leaf developmental traits.
      We also determined that these factors are able to mutually interact in a yeast
      two-hybrid assay and regulate the expression of KNOX1 genes. To circumvent the
      issue of genetic redundancy, dominant negative forms with SRDX repressor domain
      were used. Analysis of transgenic plants expressing AtTCP7-SRDX and AtTCP23-SRDX
      indicate a role of these factors in the control of cell proliferation. 

PMID- 24137172
TI  - Using cellzilla for plant growth simulations at the cellular level.
AB  - Cellzilla is a two-dimensional tissue simulation platform for plant modeling
      utilizing Cellerator arrows. Cellerator describes biochemical interactions with a
      simplified arrow-based notation; all interactions are input as reactions and are
      automatically translated to the appropriate differential equations using a
      computer algebra system. Cells are represented by a polygonal mesh of well-mixed
      compartments. Cell constituents can interact intercellularly via Cellerator
      reactions utilizing diffusion, transport, and action at a distance, as well as
      amongst themselves within a cell. The mesh data structure consists of vertices,
      edges (vertex pairs), and cells (and optional intercellular wall compartments) as
      ordered collections of edges. Simulations may be either static, in which cell
      constituents change with time but cell size and shape remain fixed; or dynamic,
      where cells can also grow. Growth is controlled by Hookean springs associated
      with each mesh edge and an outward pointing pressure force. Spring rest length
      grows at a rate proportional to the extension beyond equilibrium. Cell division
      occurs when a specified constituent (or cell mass) passes a (random, normally
      distributed) threshold. The orientation of new cell walls is determined either by
      Errera's rule, or by a potential model that weighs contributions due to
      equalizing daughter areas, minimizing wall length, alignment perpendicular to
      cell extension, and alignment perpendicular to actual growth direction. 

PMID- 24137174
TI  - Minor ailments across Canadian jurisdictions.

PMID- 24137173
TI  - The ABCC6 transporter: what lessons can be learnt from other ATP-binding cassette
      transporters?
AB  - ABC transporters represent a large family of ATP-driven transmembrane
      transporters involved in uni- or bidirectional transfer of a large variety of
      substrates. Divided in seven families, they represent 48 transporter proteins,
      several of which have been associated with human disease. Among the latter is
      ABCC6, a unidirectional exporter protein primarily expressed in liver and kidney.
      ABCC6 deficiency has been shown to cause the ectopic mineralization disorder
      pseudoxanthoma elasticum (PXE), characterized by calcification and fragmentation
      of elastic fibers, resulting in oculocutaneous and cardiovascular symptoms.
      Unique in the group of connective tissue disorders, the pathophysiological
      relation between the ABCC6 transporter and ectopic mineralization in PXE remains
      enigmatic, not in the least because of lack of knowledge on the substrate(s) of
      ABCC6 and its unusual expression pattern. Because many features, including
      structure and transport mechanism, are shared by many ABC transporters, it is
      worthwhile to evaluate if and to what extent the knowledge on the physiology and
      pathophysiology of these other transporters may provide useful clues toward
      understanding the (patho)physiological role of ABCC6 and how its deficiency may
      be dealt with. 

PMID- 24137175
TI  - A Sensitive Technique for Two-Photon Absorption Measurements: Towards Higher
      Resolution Microscopy.
AB  - High repetition rate (HRR) lasers are essential in multiphoton microscopy for
      satisfactory signal to noise at low average powers. However, HRR lasers generate
      thermal distortions in samples even with the slightest single photon absorption.
      Using an optical chopper with HRR lasers ("blanking") we demonstrate a
      femtosecond z-scan setup that effectively eliminates thermal as well as small
      linear absorption effects and precisely measures two-photon absorption (TPA)
      cross-sections of chromophores. Accurate measurement of TPA cross-sections in
      biologically relevant chromophores is especially important since the TPA spectrum
      is considerably different in regions with even minute linear absorption. Such
      blanking measurements with chopper also show enhanced fluorescence efficiency of
      the chromophores.

PMID- 24137176
TI  - Epidermal barrier: Adverse and beneficial changes induced by ultraviolet B
      irradiation depending on the exposure dose and time (Review).
AB  - Exposure of the skin to ultraviolet (UV) radiation induces various harmful
      effects in the tissues, particularly disruption of the epidermal barrier.
      However, ultraviolet B (UVB) irradiation has been applied in the treatment of
      atopic dermatitis, a skin disease in which the epidermal barrier is defective. We
      reviewed the homeostasis of the epidermal barrier and several studies
      investigating the adverse and beneficial effects caused by different doses of UVB
      irradiation in the epidermal barrier. It may be concluded that, despite the
      harmful effects of UVB irradiation on the skin, UVB irradiation is able to exert
      beneficial effects in the epidermal barrier when administered in suberythemal
      doses and over a relatively short period of time, with no clinically evident
      inflammation or barrier disruption. This may be a useful therapeutic strategy for
      the use of UVB irradiation in the treatment of skin diseases with a disrupted
      epidermal barrier, such as atopic dermatitis, while reducing or avoiding the side
      effects.

PMID- 24137177
TI  - Influence of maternal body mass index on gestational weight gain and birth
      weight: A comparison of parity.
AB  - Previous studies have revealed correlations among prepregnancy body mass index
      (BMI), gestational weight gain and the birth weight of the infant. However, as a
      variety of indices relating to the physique have been used to assess the optimal
      weight of pregnant women, no conclusions have yet been established regarding the
      Japanese population. Therefore, the aim of this study was to analyze the
      correlations among prepregnancy BMI, gestational weight gain and the birth weight
      of the infant in primiparous and multiparous females. The study was a
      retrospective analysis of pregnancy charts from a single birthing center from
      August 1998 to the end of September 2007. The subjects were primiparous (n=220)
      and multiparous (n=340) females, and the mean prepregnancy weights of the two
      groups were 52.8+/-8.8 and 54.3+/-9.0 kg, respectively. The mean prepregnancy BMI
      of the primiparous females was 20.8+/-3.1 kg/m2, compared with 21.6+/-3.5 kg/m2
      for the multiparous females, and the mean birth weights of the infants were
      3,153.0+/-364.1 g and 3,262.3+/-370.4 g for primiparous and multiparous females,
      respectively. When the correlation between the maternal factors and the birth
      weight of the infant was analyzed, the birth weight was revealed to be positively
      correlated with delivery weight and gestational weight gain in primiparous
      females. However, no correlations were observed between the birth weight of the
      infant and prepregnancy weight or BMI. In multiparous females, birth weight was
      revealed to be positively correlated with prepregnancy weight, BMI and the
      maternal delivery weight; however, no correlation was observed between the birth
      weight of the infant and gestational weight gain. The results of the present
      study also demonstrated that there were significant differences between the
      primiparous and multiparous females, with regard to gestational weight gain and
      weight reduction following delivery. The study indicated that the factors
      influencing birth weight may be different for primiparous and multiparous
      females.

PMID- 24137178
TI  - The microtubule depolymerizing agent CYT997 effectively kills acute myeloid
      leukemia cells via activation of caspases and inhibition of PI3K/Akt/mTOR pathway
      proteins.
AB  - The orally active microtubule-depolymerizing agent CYT997 is potently cytotoxic
      to a variety of tumors in vitro and in vivo. However, the effects of this agent
      on acute myeloid leukemia (AML) cells and its mechanisms are unknown. The present
      study demonstrated that CYT997 effectively inhibited the growth of AML cells in
      vitro. Treatment of AML cells with CYT997 resulted in G2/M phase cell cycle
      arrest, and induced apoptosis through the activation of extrinsic and intrinsic
      apoptotic pathways. Furthermore, CYT997 induced cell death in CD123+ leukemia
      cells and significantly reduced leukemia colony formation. CYT997 was also
      demonstrated to exert dual effects on the expression of PI3K/Akt and mechanistic
      target of rampamycin (mTOR) signaling pathway proteins. Therefore, CTY997, used
      alone or in combination with chemotherapy, may represent a promising approach for
      the treatment of AML.

PMID- 24137179
TI  - Comparison between absolute ethanol and bleomycin for the treatment of venous
      malformation in children.
AB  - The aim of this study was to investigate the therapeutic efficacies and treatment
      effects of absolute ethanol and bleomycin for the treatment of venous
      malformation (VM) in children. A total of 138 children with VM were randomly
      divided into two groups; 75 patients were treated with absolute ethanol, while a
      further 63 were treated with bleomycin under general anesthesia between February
      2009 and February 2012. The treatment outcome and complications were observed in
      the two groups and the treatment efficacy was classified as one of four
      categories: cured, markedly effective, effective and ineffective. The curative
      effect was analyzed 6-24 months after treatment, with a mean of 15 months.
      Absolute ethanol was effective (cured, markedly effective or effective) in 71
      cases and bleomycin was effective in 41 cases, and the difference between the
      effective rates was considered to be statistically significant (chi2=19.6,
      P<0.05). In the absolute ethanol group there were 14 cases with skin necrosis, 17
      patients had serious localized swelling which required additional treatment,
      three patients developed muscle fibrosis and one patient suffered a brain
      embolism. In the bleomycin group there were five cases with skin necrosis and the
      difference in the incidence of adverse reactions was considered to be
      statistically significant (chi2=18.8, P<0.05). The curative effect of
      sclerotherapy for VM is clear, and absolute ethanol is the most effective
      sclerosing agent, but has a greater incidence of adverse side-effects than
      bleomycin. The major side-effect is skin necrosis. The choice of sclerotherapy
      depends on the classification of VM in children.

PMID- 24137180
TI  - The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of
      endothelial cells against advanced glycation end products through the nuclear
      factor kappaB pathway.
AB  - Accumulating evidence has demonstrated that the Rho/Rho-associated protein kinase
      (Rho/ROCK) and nuclear factor kappaB (NF-kappaB) signaling pathways are involved
      in the pathogenesis of diabetic vascular injury. In this study, we investigated
      the beneficial effects of fasudil, a ROCK inhibitor, on vascular endothelial
      injury induced by advanced glycation end products (AGEs) in vitro. Human
      umbilical vein endothelial cells (HUVECs) were stimulated with AGEs and AGEs plus
      fasudil in various concentrations for different time periods. Monocyte
      endothelial cell adhesion, vascular cell adhesion molecule-1 (VCAM-1) and
      monocyte chemoattractant protein-1 (MCP-1) expression, protein expression and
      activation of Rho/ROCK, activation of NF-kappaB and reactive oxygen species (ROS)
      production were evaluated. Fasudil suppressed AGE-induced monocyte-endothelial
      adhesion. Fasudil also reduced the mRNA and protein expression of VCAM-1 and MCP
      1 in a concentration- and time-dependent manner. Moreover, increases in the
      protein levels of Rho/ROCK and ROCK activity mediated by AGEs were inhibited by
      the addition of fasudil. Additionally, fasudil attenuated AGE-induced NF-kappaB
      dependent transcriptional activity and inhibition of NF-kappaB (IkappaB)
      phosphorylation. ROS production induced by AGEs was also reduced by fasudil in
      HUVECs. The results suggest that ROCK inhibition may protect the vascular
      endothelium against AGE-induced monocyte-endothelial adhesion in vitro through
      the reduction of ROS generation and the downregulation of NF-kappaB signaling.
      Thus, ROCK inhibition may be a novel therapeutic approach for the treatment of
      vascular complications in diabetes.

PMID- 24137181
TI  - Thromboangiitis obliterans in two brothers.
AB  - Two brothers (case 1 and case 2) with erythema nodosum were diagnosed with
      thromboangiitis obliterans (TAO). The patients were treated with compounds
      including Danshen Dripping Pills, Fufang Danshen Diwan and Salvia
      tetramethylpyrazine. The patients were also treated with fibro-blast growth
      factor to promote epidermal growth and Bayaspirin enteric-coated tablets to
      reduce platelet aggregation. The polysaccharide nucleic acid fraction of Bacillus
      Calmette-Guerin and compound glycyrrhizin tablets were taken to improve immune
      function. Following treatment, case 2 had reduced pain levels in the left foot.
      The ulcer on the first toe of the left foot had decreased in size, with a
      reduction in pus secretions and inflammation. Case 1 demonstrated a reduction in
      pus secretion from the ulcer. However, the area of the ulcer had increased,
      spreading to the fifth toe with gangrene. A tendon had become exposed on the
      right foot, which was broken and induced severe pain.

PMID- 24137182
TI  - Placement of vena cava filter via percutaneous puncture of the great saphenous
      vein.
AB  - The aim of this study was to investigate the feasibility and safety of vena cava
      filter (VCF) placement via percutaneous puncture of the great saphenous vein
      (GSV) in the prevention of pulmonary embolisms. Using ultrasound positioning, VCF
      placement via percutaneous puncture of the GSV was performed on 12 patients with
      deep vein thrombosis (DVT) in the lower extremities. Transcatheter thrombolysis
      was conducted simultaneously. The postoperative filter position, puncture wound
      recovery and fluency of the GSV were observed. All filters were successfully
      released, with accurate positioning. No hematoma was observed at the puncture
      point during the perioperative period. In certain patients, local petechiae
      appeared around the puncture point during the thrombolysis period, which did not
      require special treatment. Re-examination using ultrasound revealed unobstructed
      blood flow in the GSV. VCF placement via percutaneous puncture of the GSV is a
      new filter placement method. The feasibility and safety of this method for the
      prevention of pulmonary embolisms has been demonstrated in a small number of
      sample cases.

PMID- 24137183
TI  - Multiple pulmonary nodules with high metabolic activity: Potential benefit of
      multiple nodule biopsies by video-assisted thoracic surgery: A case report.
AB  - The aim of this study was to assess complex cases of multiple pulmonary nodules
      (PNs) with high metabolic activity that may have benefited from being managed in
      a manner outside the formal guidelines. The study describes the case of a patient
      with multiple highly metabolically-active PNs, where an original diagnosis of
      lung cancer metastasis was proposed. Following a failed transbronchial lung
      biopsy (TBLB), multiple nodule biopsies by video-assisted thoracic surgery (VATS)
      were performed, and a diagnosis of lymphoepithelioma-like carcinoma (LELC; stage
      IA) and tuberculosis was reached. This case report demonstrated that multiple
      nodule biopsies by VATS were effective and were able to improve the prognosis
      without delay.

PMID- 24137184
TI  - Construction and characterization of a recombinant human adenovirus vector
      expressing bone morphogenetic protein 2.
AB  - The aim of this study was to construct and characterize a novel recombinant human
      adenovirus vector expressing bone morphogenetic protein 2 (BMP2) and green
      fluorescent protein (GFP). The BMP2 gene in the plasmid pcDNA3-BMP2 was sequenced
      and the restriction enzyme recognition sites were analyzed. Following mutagenesis
      using polymerase chain reaction (PCR), the gene sequence after the translation
      termination codon was removed and new restriction sites were added. The mutated
      BMP2 gene (BMP2+ gene) was cloned into an adenovirus shuttle vector to obtain
      pShuttle cytomegalovirus (CMV)-BMP2+-internal ribosome entry site (IRES)-hrGFP-1.
      The adenovirus plasmid pAd CMV-BMP2+-IRES-hrGFP-1 was constructed by homologous
      recombination and was transfected into HEK293A cells, followed by adenovirus
      packaging. pAd CMV-BMP2 was used as the control. The two types of adenovirus were
      transfected into marrow stromal cells (MSCs). The expression of BMP2 and GFP, as
      well as the alkaline phosphatase (ALP) activity of expressed BMP2 were detected.
      Following mutagenesis, the BMP2 gene sequence and recombinant adenovirus vector
      were as predicted. The novel adenovirus vector expressed both BMP2 and GFP,
      indicating that a novel recombinant human adenovirus vector expressing BMP2 had
      been successfully constructed.

PMID- 24137185
TI  - Bioinformatic prediction of epitopes in the Emy162 antigen of Echinococcus
      multilocularis.
AB  - The aim of the present study was to predict the secondary structure and the T-
      and B-cell epitopes of the Echinococcus multilocularis Emy162 antigen, in order
      to reveal the dominant epitopes of the antigen. The secondary structure of the
      protein was analyzed using the Gamier-Robson method, and the improved self
      optimized prediction method (SOPMA) server. The T- and B-cell epitopes of Emy162
      were predicted using Immune Epitope Database (IEDB), Syfpeithi, Bcepred and
      ABCpred online software. The characteristics of hydrophilicity, flexibility,
      antigenic propensity and exposed surface area were predicted. The tertiary
      structure of the Emy162 protein was predicted by the 3DLigandSite server. The
      results demonstrated that random coils and beta sheets accounted for 34.64 and
      21.57% of the secondary structure of the Emy162 protein, respectively. This was
      indicative of the presence of potential dominant antigenic epitopes in Emy162.
      Following bioinformatic analysis, numerous distinct antigenic epitopes of Emy162
      were identified. The high-scoring T-cell epitopes were located at positions 16
      29, 36-39, 97-103, 119-125 and 128-135, whilst the likely B-cell epitopes were
      located at positions 8-10, 19-25, 44-50, 74-81, 87-93, 104-109 and 128-136. In
      conclusion, five T-cell and seven B-cell dominant epitopes of the Emy162 antigen
      were revealed by the bioinformatic methods, which may be of use in the
      development of a dominant epitope vaccine.

PMID- 24137186
TI  - Investigation into the optimal surgical conditions for coronary artery ligation
      for establishing a myocardial infarction model in mice.
AB  - In the present study, the left anterior descending coronary arteries of mice
      under anesthesia were ligated, and the optimal surgical conditions for coronary
      artery ligation (CAL) in the establishment of a myocardial infarction (MI) mouse
      model were investigated. All mice that survived were sacrificed seven days
      subsequent to the successful surgery. Body weight, blood serum and heart tissues
      were obtained for further analysis or biochemical and histopathological
      examinations. The survival rate of the mice following the CAL procedure was 70%.
      The aspartate aminotransferase (AST), creatine kinase (CK) and lactate
      dehydrogenase (LDH) concentrations in the serum of the experimental mice were
      significantly increased compared with those of the control mice, which reflected
      the enzyme release from the infarcted myocardial cells. Histopathological
      examination showed different degrees of MI in the heart tissues of the
      experimental mice. The results indicate that an MI model in mice may be
      successfully established using CAL under the surgical conditions utilized in the
      present study. These conditions were cost effective and the results may be
      replicated by laboratories that are less well-equipped.

PMID- 24137187
TI  - In vitro study on the feasibility of magnetic stent hyperthermia for the
      treatment of cardiovascular restenosis.
AB  - Thermal treatment or hyperthermia has received considerable attention in recent
      years due to its high efficiency, safety and relatively few side-effects. In this
      study, we investigated whether it was possible to utilize targeted thermal or
      instent thermal treatments for the treatment of restenosis following percutaneous
      transluminal coronary angioplasty (PTCA) through magnetic stent hyperthermia
      (MSH). A 316L stainless steel stent and rabbit vascular smooth muscle cells
      (VSMCs) were used in the present study, in which the inductive heating
      characteristics of the stent under alternative magnetic field (AMF) exposure, as
      well as the effect of MSH on the proliferation, apoptosis, cell cycle and
      proliferating cell nuclear antigen (PCNA) expression of the rabbit VSMCs, were
      evaluated. The results demonstrated that 316L stainless steel coronary stents
      possess ideal inductive heating characteristics under 300 kHz AMF exposure. The
      heating properties were shown to be affected by the field intensity of the AMF,
      as well as the orientation the stent axis. MSH had a significant effect on the
      proliferation and apoptosis of VSMCs, and the effect was temperature-dependent.
      While a mild temperature of 43 degrees C demonstrated negligible effects on the
      growth of VSMCs, MSH treatment above 47 degrees C effectively inhibited the VSMC
      proliferation and induced apoptosis. Furthermore, a 47 degrees C treatment
      exhibited a significant and long-term inhibitory effect on VSMC migration. The
      results strongly suggested that MSH may be potentially applied in the clinic as
      an alternative approach for the prevention and treatment of restenosis.

PMID- 24137188
TI  - Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective
      response to chemotherapy in patients with non-small cell lung cancer.
AB  - Diagnostic tools capable of predicting early responses to chemotherapy are
      required to improve the individual management of cancer patients. The present
      study aimed to evaluate the prognostic significance of the serum tumor markers
      CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE),
      carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different
      chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A
      total of 276 patients with postoperative stage I-IV NSCLC were retrospectively
      reviewed. The five tumor markers were measured before and after at least two
      cycles of chemotherapy using an electrochemiluminescent assay. Multivariate
      analysis revealed that performance status, age, postoperative stage and surgery
      were significantly associated with the response to chemotherapy. High baseline
      CYFRA 21-1 and CA 19-9 levels were associated with poor effectiveness of
      chemotherapy. Significant reductions in CYFRA 21-1 levels were associated with a
      positive response to various chemotherapy regimens. CEA, CA 125 and CA 19-9
      expression was only associated with a positive response in patients receiving
      paclitaxel, docetaxel, pemetrexed and the epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI). NSE expression was only associated with a
      positive response to gemcitabine. Receiver operating characteristic (ROC) curve
      analysis indicated that CYFRA 21-1 is the most sensitive of the tumor markers in
      predicting the response to chemotherapy. Serum CYFRA 21-1 is a useful surrogate
      marker for predicting the response to different chemotherapy regimens used to
      treat NSCLC and is a more sensitive marker than CEA, CA125, CA19-9 and NSE.

PMID- 24137189
TI  - High glucose enhances LPS-stimulated human PMVEC hyperpermeability via the NO
      pathway.
AB  - Chronic hyperglycemia is an established risk factor for endothelial damage. It
      remains unclear, however, whether brief hyperglycemic exposure exacerbates the
      damage to vascular endothelial cells induced by endotoxin. We hypothesize that
      brief hyperglycemic exposure enhances the permeability of the endothelium
      following stimulation with lipopolysaccharide (LPS). Correlations between
      modulation of nitric oxide synthase (NOS) pathways and altered endothelial
      homeostasis have been studied and demonstrated in various pathophysiological
      conditions. NOS activities are regulated by endogenous inhibitors, including
      asymmetric dimethylarginine (ADMA), which is metabolized by dimethylarginine
      dimethylaminohydrolase (DDAH). Since previous data demonstrated that endothelial
      dysfunction may be related to reduced expression and/or activity of DDAH, in this
      study, we aimed to determine the effect of increased glucose levels on pulmonary
      microvascular endothelial cell (PMVEC) permeability, including effects on the NOS
      pathways. Human PMVECs were incubated with normal (5.5 mM) and high (33 mM)
      concentrations of D-glucose for 5 days to create a monolayer of cells prior to
      LPS stimulation (10 MUg/ml) for 12 h. When stimulated with LPS, cells incubated
      with a high glucose (HG) concentration had significant microfilament
      rearrangement compared with cells incubated with a normal glucose concentration,
      as determined by immunofluorescence. Scanning electron microscopy revealed a
      larger average diameter and increased number of fenestrae on the hyperglycemic
      PMVECs when stimulated with LPS, compared with PMVECs cultured with a normal
      glucose concentration. The results demonstrated that a high concentration of
      glucose increases the LPS-stimulated horseradish peroxidase (HRP) permeability
      compared with a normal concentration of glucose. Furthermore, a HG concentration
      upregulated LPS-stimulated inducible NOS (iNOS) production and down-regulated
      endothelial NOS (eNOS) and DDAH-2 expression. Hyperglycemia significantly
      increased LPS-stimulated nitrite/nitrate production (stable NO end-products). Our
      results, thus, demonstrate that in vitro HG concentrations exacerbate LPS
      stimulated cytoskeletal rearrangement and hyperpermeability of an endothelial
      monolayer, and cause further imbalance of the NO pathway. These results suggest
      that it is important to manage even short-term increases in blood glucose,
      particularly following acute infection.

PMID- 24137190
TI  - Two-dimensional strain ultrasound speckle tracking as a novel approach for the
      evaluation of right hemidiaphragmatic longitudinal deformation.
AB  - The diaphragm is an important respiratory organ. The aim of this study was to
      quantitatively evaluate the longitudinal deformation of the right hemidiaphragm
      in normal subjects using two-dimensional strain ultrasound speckle tracking.
      Twenty-one healthy subjects were enrolled in this study. GE Healthcare Vivid E9
      equipment with M5S probe and Q-analysis software were used. Negative strain
      values first appeared in the zone of apposition and then in the crura of the
      right hemidiaphragm in the inspiratory phase; the dome of the diaphragm was
      observed to be passively stretched. The longitudinal strain of the right
      hemidiaphragm in the zone of apposition was higher than that in the crura in
      forced breathing (P=0.024). The strains of the whole diaphragm and the zone of
      apposition changed significantly in quiet (P=0.000) and forced breathing
      (P=0.005). Ultrasound strain imaging may quantitatively assess diaphragm
      deformation and provide another useful modality for evaluating diaphragm
      kinetics.

PMID- 24137191
TI  - Expression of c-Fos and c-Jun in adjacent cervical spinal cord segments following
      C7 nerve root rhizotomy in rats: Indication of a neural pathway between adjacent
      cervical spinal cord segments.
AB  - Cervical radiculopathy is a common disease in clinical practice. However, the
      symptoms are not confined to the affected spinal cord segment indicated by
      magnetic resonance imaging (MRI) findings. In the present study, we measured c
      Fos and c-Jun expression in ipsilateral and adjacent cervical spinal cord
      segments following C7 nerve root rhizotomy, to determine whether there is a
      neural pathway between adjacent cervical spinal cord segments. Forty-eight adult
      male Wistar rats were randomly divided into two groups: the C7 rhizotomy group
      (rhizotomy group, n=24) and the sham-operated group (sham group, n=24). The right
      C7 nerve root was completely cut off in the rhizotomy group, while it was exposed
      but not cut in the sham group. The expression of c-Fos and c-Jun in cervical
      spinal cord segments was detected by immunohistochemistry at 2 and 4 h after
      surgery. We observed that the number of c-Fos- and c-Jun-positive neurons in
      ipsilateral C5-7 segments were significantly increased at 2 and 4 h after C7
      nerve root rhizotomy (P<0.05 vs. the sham group). The location of c-Fosand c-Jun
      positive neurons in C5-7 gray matter was similar in the rhizotomy and sham
      groups, which was mainly in lamina IX of the anterior horn and laminae I-II of
      the dorsal horn of the spinal cord. However, the number of c-Fos- and c-Jun
      positive neurons in the C5-7 gray matter was significantly reduced at 4 h after
      surgery compared with the number 2 h after surgery. The location of c-Fos- and c
      Jun-positive neurons at 4 h was similar with that at 2 h. Therefore, there may be
      a neural pathway between ipsilateral adjacent cervical spinal cord segments. This
      may be one possible explanation as to why the radicular symptoms of cervical
      radiculopathy are not confined to the affected spinal cord segment shown by MRI.

PMID- 24137192
TI  - Diagnosis and multimodal therapy for extragastrointestinal stromal tumor of the
      prostate: A case report.
AB  - Extragastrointestinal stromal tumors (EGISTs), which are neoplasms outside the
      digestive tract, are predominantly observed in the greater omentum and
      retroperitoneum. The clinicopathological and molecular characteristics of EGISTs
      are similar to those of gastrointestinal stromal tumors (GISTs). EGISTs
      originating from the prostate are extremely rare. In this study, we report a case
      of a prostatic EGIST in a 39-year-old male, who presented with frequency,
      urgency, dysuria and a prostatic mass. A 10-core transrectal ultrasound-guided
      prostate biopsy was performed, and the histological and immunohistochemical
      results confirmed the diagnosis of EGIST. The patient received a radical
      prostatectomy, followed by targeted therapy with imatinib (400 mg, daily) for 1
      year. Neither recurrence nor metastasis was detected at a 24-month follow-up.

PMID- 24137193
TI  - Induction of apoptosis by sarijang, a bamboo salt sauce, in U937 human leukemia
      cells through the activation of caspases.
AB  - Sarijang is a bamboo salt soy sauce, containing extracts of Rhynchosia nulubilis,
      sulfur-fed duck, dried bark of Ulmus davidiana and Allium sativum, which has been
      demonstrated to exert anti-inflammatory and antitumor activity. However, the
      cellular and molecular mechanisms of action of sarijang have not yet been
      elucidated. In the present study, we investigated the pro-apoptotic effects of
      sarijang in an in vitro U937 human leukemia cell model. Treatment with sarijang
      resulted in a concentration-dependent growth inhibition of the cells, coupled
      with the characteristic morphological features of apoptosis. The induction of the
      apoptotic cell death of the U937 cells by sarijang exhibited a correlation with
      the upregulation of death receptor 4 (DR4), the downregulation of members of the
      inhibitor of apoptosis protein (IAP) family, including survivin and cellular IAP
      (cIAP)-1, and the cleavage of Bid. Apoptosis-inducing concentrations of sarijang
      also induced the activation of caspases (caspase-3, -8 and -9), accompanied by
      proteolytic degradation of poly(ADP-ribose)-polymerase, beta-catenin and
      phospholipase C-gamma1. However, the apoptosis induced by sarijang was
      significantly inhibited by z-VED-fmk, a pan-caspase inhibitor, which demonstrated
      the importance of caspases in the process. These results suggested that sarijang
      may be a potential chemotherapeutic agent for use in the control of U937 human
      leukemia cells. Further studies are required to identify the active compounds in
      sarijang.

PMID- 24137194
TI  - Treatment of superficial infantile hemangiomas with timolol: Evaluation of short
      term efficacy and safety in infants.
AB  - Timolol has been demonstrated to be efficacious in the topical treatment of
      superficial infantile hemangiomas (IHs). We conducted a prospective study to
      evaluate the short-term efficacy and safety of timolol in the treatment of
      superficial IH in Chinese infants. From March to November 2012, 124 patients with
      superficial IHs were included in the prospective study. The patients were divided
      into two groups: treatment (101 patients, the timolol drops were administered on
      the surface of the lesions three times daily, and erythromycin ointment was
      applied around the lesions) and observation (23 patients, without treatment). The
      results were categorized into three grades: class 1 (ineffective), class 2
      (controlled growth) and class 3 (promoted regression). Within one week of the
      initiation of timolol treatment, a number of the lesions became softer and
      lighter in color. Four months following the initiation of timolol treatment, the
      overall response was class 1 in eight patients (7.9%), class 2 in 36 patients
      (35.6%) and class 3 in 57 patients (56.4%). Complete tumor regression was
      observed in 12 patients. No adverse effects were recorded during the treatment
      period. Among the patients in the observation group, there were 15 class 1
      patients (65.2%), seven class 2 patients (30.4%) and only one class 3 patient
      (4.3%). In conclusion, timolol is an effective and safe treatment for superficial
      IH. In addition, it may be used in the treatment of proliferative superficial IH,
      particularly in infants within 6 months of age.

PMID- 24137195
TI  - Endoscopic submucosal dissection of gastric fundus subepithelial tumors
      originating from the muscularis propria.
AB  - Endoscopic resection of gastric subepithelial tumors (SETs) carries a high risk
      of perforation, particularly for tumors located at the gastric fundus and
      originating from the muscularis propria. Based on our experience with endoscopic
      submucosal dissection (ESD) and a novel endoscopic device, namely the 'Resolution
      clip' for the endoscopic closure of iatrogenic upper gastrointestinal (upper GI)
      perforations, we evaluated the clinical feasibility and safety of ESD for gastric
      fundus subepithelial tumors originating from the muscularis propria. In this
      prospective study, 11 consecutive patients who presented with gastric SETs <=3 cm
      in diameter were enrolled. Regardless of whether perforation occurred, the
      gastric wall defect was closed with clips. The patients were followed up after
      the surgery. Endoscopic resection was successfully performed in 10 patients;
      however, in one patient a pure endoscopic approach was impossible as the lesion
      was severely adhered to surrounding tissue, and a switch to laparoscopic wedge
      resection was necessary. The mean resected tumor size was 18.8*17.2 mm and the
      mean surgery time of the 10 patients with ESD was 81 min (range 45-130 min).
      Histological diagnosis was gastrointestinal stromal tumor (GIST) in eight lesions
      [very low risk according to the National Institutes of Health (NIH) risk
      classification] and leiomyoma in three lesions. Perforation occurred in 3/10
      patients. Gastric closure with the Resolution clips was performed successfully in
      all cases. Early post-ESD bleeding (EPEB) occurred in one patient. Basic ferric
      sulfate solution was sprayed during the upper GI endoscopy examination and the
      bleeding stopped. No complications occurred and the follow-up was unremarkable.
      In this early study, ESD using the Resolution clip was demonstrated to be a
      feasible and minimally invasive treatment for gastric fundus subepithelial tumors
      originating from the muscularis propria.

PMID- 24137196
TI  - Clinical values of urinary IL-6 in asymptomatic renal hematuria and renal
      hematuria with proteins.
AB  - Renal hematuria is caused by glomerular disease. Under pathological conditions,
      the distribution of interleukin-6 (IL-6) in kidney tissue is abnormal and urinary
      IL-6 levels are increased. Abnormal IL-6 secretion promotes the hyperplasia of
      mesangial cells and matrix and, thus, affects the permeability of the glomerular
      filtration membrane. Therefore, the detection of urinary IL-6 levels in patients
      with renal hematuria is beneficial for disease evaluation. A total of 82 patients
      with primary renal hematuria were divided into group 1 (UPr/24 h < 150 mg; pure
      hematuria group), group 2 (150 mg <= UPr/24 h <= 1,000 mg) and group 3 (UPr/24 h
      > 1,000 mg). A total of 30 normal individuals were selected as the controls. The
      urinary IL-6 levels were detected by the enzyme-linked immunosorbent assay
      (ELISA) method and a renal biopsy was conducted. The urinary IL-6 levels and
      renal pathological damage scores in groups 1 and 2 were significantly reduced
      compared with those in group 3, (P<0.001 and 0.01, respectively), with no
      significant difference between groups 1 and 2 (P>0.05). The correlation
      coefficient (r) of urinary IL-6 with 24 h urinary protein (UPr/24 h) in groups 1,
      2 and 3 was 0.017, 0.045 and 0.747, respectively, and that of urinary IL-6 with
      renal pathological damage score was 0.627, 0.199 and 0.119, respectively. The
      UPr/24 h was significantly correlated with IL-6 level (r=0.7320, P<0.000). In
      group 1, the urinary IL-6 levels were correlated with the degree of renal
      pathological damage. A positive correlation was observed between urinary IL-6
      levels and UPr/24 h.

PMID- 24137197
TI  - Reconstruction of the portal vein with 64-slice spiral CT of bile duct
      obstruction.
AB  - The aim of this study was to evaluate 64-slice spiral CT image reconstruction of
      the portal vein in biliary obstruction. A total of 34 clinical patients with
      biliary obstruction were confirmed by 64-slice spiral CT scanning with portal
      venous phase multi-planar reconstruction (MPR) of the biliary tract, curved
      planar reconstruction (CPR), thin-slab minimum-intensity projection (TS-MinIP)
      and maximum intensity projection (MIP). The reconstructed images were reviewed to
      further assess the position and cause of the biliary obstruction and to judge the
      accuracy of diagnosis. The 64-slice spiral CT image reconstruction of the biliary
      obstructions determined the causes with an accuracy of 88.2% (30/34) and
      identified the location of the obstruction with an accuracy of 100%. A 64-slice
      spiral CT reconstructed image of the portal bile duct lesions was generated,
      which indicated the lesion morphology, location and anatomical relationship with
      surrounding tissues, secondary biliary stricture and the degree of expansion and
      is of great clinical value in the characterization and preoperative evaluation of
      biliary disease.

PMID- 24137198
TI  - Correlation between aortic/carotid atherosclerotic plaques and cerebral
      infarction.
AB  - The aim of this study was to investigate the correlation between aortic/carotid
      atherosclerotic plaques and cerebral infarction. We examined 116 cases of
      cerebral infarction using transcranial Doppler ultrasound in order to exclude
      cerebrovascular stenosis. Transesophageal echocardiography and color Doppler
      ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid
      atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116
      cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%).
      The difference in the incidence of various types of infarction between APP
      severity levels was significant (P<0.01). Of the 116 cases, 64 had CAPs (55.2%),
      including 46 with unstable plaque (39.7%). The difference in the incidence of
      various types of infarction between CAP stability levels was significant
      (P<0.01). The results indicate that moderate/severe AAP and unstable CAP are
      significant causes of embolic infarction without stenosis in the internal carotid
      arteries.

PMID- 24137199
TI  - The complete recanalization of PICC-related venous thrombosis in cancer patients:
      A series of case reports.
AB  - In this study, cancer patients with venous thrombosis associated with the use of
      peripherally inserted central catheters (PICCs) underwent complete recanalization
      by the administration of Panax notoginseng saponins (PNS), which vary from
      heparin or urokinase in that they do not have the same risks associated with
      thrombolysis, including bleeding. To the best of our knowledge, this is the first
      study concerning the treatment of cancers with PNS to be reported in the
      literature. Three cancer patients aged 30-50 years old, two females and one male,
      were subjected to chemotherapy. On the first day of chemotherapy, a PICC was
      inserted into the right basilic vein with its tip in the superior vena cava. On
      the third day of chemotherapy, pain, swelling and skin flushing started. In the
      following days, particularly days 10-13, a Doppler ultrasound examination
      confirmed a long thrombus along the PICC line in the axillary vein and brachial
      veins in each patient. The patients rejected the insertion of an inferior vena
      cava filter, and neither heparin nor urokinase were administered due to contra
      indications. An injection of PNS (200 mg) was administered every day. On days 20
      28 of chemotherapy, the thrombus in the axillary and brachial veins disappeared
      in the three patients. It was concluded that PNS promote blood circulation, which
      prevents blood stasis and reduces the toxicity of cisplatin. The results suggest
      that PNS are a feasible and effective treatment option for many types of cancer,
      but have a broader clinical impact on cancer patients with PICC-related venous
      thrombosis. Therefore, this study is an original case report of particular
      interest to cancer patients with PICC-related venous thrombosis.

PMID- 24137200
TI  - Evidence-based study on antithrombotic therapy in patients at risk of a stroke
      with paroxysmal atrial fibrillation.
AB  - The aim of the present study was to determine the optimal intensity of
      anticoagulation therapy in elderly patients with paroxysmal atrial fibrillation
      (PAF), using aspirin and varied concentrations of warfarin. Elderly patients with
      PAF (n=1,162) who met the inclusion criteria of the study and were at middle or
      high-risk of a stroke were investigated. Patients were divided into six groups
      (four high-risk groups and two middle-risk groups). Patients were treated with
      aspirin or varied concentrations of warfarin. The primary endpoint events,
      secondary endpoint events, major bleeding events and minor bleeding events were
      observed and compared. In high-risk elderly patients, warfarin significantly
      reduced primary and secondary endpoint events, total primary events and total
      events compared with aspirin. In middle-risk elderly patients, for all the events
      warfarin demonstrated no significant difference compared with aspirin. In high
      risk patients with PAF, when the concentration of warfarin was adjusted to target
      international normalized ratio (INR) range 1.7-2.5, the primary and secondary
      endpoint events, total primary events and total events were significantly lower
      (P<0.05), compared with aspirin and warfarin at INR 1.2-1.6. When the intensity
      of warfarin was adjusted to the target INR 2.6-3.0, the primary and secondary
      endpoint events were significantly lower (P<0.05) compared with aspirin and
      warfarin INR at 1.2-1.6. This study determined that in high-risk elderly patients
      with PAF, warfarin is recommended for anticoagulation with an optimal INR range
      of 1.7-2.5. In patients at a middle-risk of a stroke, aspirin is the recommended
      treatment as an antithrombotic as results have indicated that there is limited
      benefit in the use of warfarin.

PMID- 24137201
TI  - Anti-inflammatory effects of escin are correlated with the glucocorticoid
      receptor/NF-kappaB signaling pathway, but not the COX/PGF2alpha signaling
      pathway.
AB  - In China, escin has been widely used in the clinic as a potent anti-inflammatory
      drug. Previous studies have indicated that escin exerts its anti-inflammatory
      effect by enhancing the release of glucocorticoids (GCs) and prostaglandin
      F2alpha (PGF2alpha), and this has been documented in the drug description.
      However, our previous studies demonstrated that escin did not increase the
      secretion of GCs, but instead elevated the protein expression of the GC receptor
      (GR), which may have repressed nuclear factor (NF)-kappaB-mediated gene
      expression. The aim of this study was to determine the functions of NF-kappaB and
      PGF2alpha with regard to the anti-inflammatory effect of escin. We investigated
      the anti-inflammatory effects of dexamethasone, diclofenac and escin against
      carrageenan-induced paw edema in rats, and observed that escin exerted a GC-like
      anti-inflammatory effect. In addition, we studied the role of PGF2alpha in the
      anti-inflammatory effect exerted by escin in an acetic acid-induced capillary
      permeability model in mice. The results revealed that the coadministration of
      escin and diclofenac, a potent prostaglandin-synthesis inhibitor, did not affect
      the anti-inflammatory effect of escin. Furthermore, we investigated the function
      of NF-kappaB with regard to the anti-inflammatory effect exerted by escin in
      lipopolysaccharide (LPS)-treated mice, and demonstrated that escin significantly
      inhibited the expression of NF-kappaB. These results suggest that escin has a GC
      like anti-inflammatory effect, and that its mechanisms may be correlated with the
      GC receptor/NF-kappaB signaling pathway, but not the COX/PGF2alpha signaling
      pathway.

PMID- 24137202
TI  - In vitro antioxidative activity of yellow tea and its in vivo preventive effect
      on gastric injury.
AB  - Yellow tea is a traditional Chinese drink widely used in Asia. The aim of this
      study was to determine the antioxidant activity of yellow tea and its preventive
      effect on gastric injury. The antioxidant effects were determined by measuring
      the 1,1-diphenyl-2-picryhydrazyl (DPPH) free radical- and hydroxyl radical
      scavenging activity. The yellow tea extract demonstrated high antioxidant
      activity in the assays of DPPH and hydroxyl radical-scavenging activity.
      Additionally, an animal model was used to investigate the preventive effect of
      yellow tea on gastric injury. High concentrations of yellow tea reduced the
      levels of the serum pro-inflammatory cytokines interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha to a greater extent than low concentrations. The
      extent of the gastric injury was significantly reduced by yellow tea, which
      demonstrated its anti-inflammatory properties. Yellow tea demonstrated the
      strongest inhibitory effect (74.6%) against gastric injury when administered at a
      dose of 1,000 mg/kg by gavage. These results suggest that yellow tea possesses
      good antioxidant activity and a preventive effect on gastric injury in vivo.

PMID- 24137203
TI  - Effect of herba centellae on the expression of HGF and MCP-1.
AB  - The aim of this study was to explore the effects of herba centellae on protein
      and mRNA expression of hepatocyte growth factor (HGF), and monocyte chemotactic
      protein-1 (MCP-1) in renal tubulointerstitial fibrosis (TIF). A unilateral
      ureteral obstruction (UUO) model was established in 50 male Sprague Dawley (SD)
      rats. Blood samples were collected and the blood urea nitrogen (BUN) levels,
      serum creatinine (Scr), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels were measured. Immunohistochemistry (IHC) detected
      the localization and expression levels of HGF and MCP-1. In addition,
      quantitative polymerase chain reaction (qPCR) detected the mRNA expression of HGF
      and MCP-1. Thirty rats were used to prepare the rat serum containing drug by cell
      culture, and qPCR and immunocytochemistry (ICC) were performed to examine the
      mRNA and protein expression of HGF and MCP-1. MCP-1 and its mRNA expression was
      significantly higher in rat renal interstitium of the UUO group and cells of the
      transforming growth factor-beta1 (TGF-beta1) stimulation group compared with that
      of the control group (P<0.01). MCP-1 and its mRNA expression in the drug
      intervention group were significantly reduced compared with that of the UUO model
      group (P<0.01). However, MCP-1 and its mRNA expression in the high-dose herba
      centellae group was significantly lower compared with that of the low-dose herba
      centellae group (P<0.01). Furthermore, HGF and its mRNA expression significantly
      increased in the drug intervention group (P<0.01), and expression in the high
      dose group was significantly higher compared with that of the low-dose group
      (P<0.01), but similar to that of the fosinopril group (P>0.05). The levels of BUN
      decreased in the drug intervention group; however, no significant differences
      were determined in Scr, ALT and AST levels. Herba centellae may have inhibited
      MCP-1 and its mRNA expression through the upregulation of HGF and its mRNA
      expression, in order to achieve resistance to TIF without showing evident
      hepatorenal toxicity.

PMID- 24137204
TI  - Correlation of the BACH1 Pro919Ser polymorphism with breast cancer risk: A
      literature-based meta-analysis and meta-regression analysis.
AB  - Recent investigations have suggested that common genetic polymorphisms in BRCA1
      associated C-terminal helicase 1 (BACH1) are important in the development of
      breast cancer. However, individually published studies and previous meta-analyses
      have demonstrated inconclusive results. The aim of this meta-analysis was to
      derive a more precise estimation of the correlation between a common polymorphism
      [proline (Pro) 919 serine (Ser); rs4986764 C>T] in the BACH1 gene and
      susceptibility to breast cancer. A literature search of PubMed, Embase, Web of
      Science and Chinese BioMedicine (CBM) databases was conducted on articles
      published prior to March 1, 2013. Crude odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated. Eleven case-control studies were included with a
      total of 6,903 breast cancer cases and 8,154 healthy controls. The meta-analysis
      results revealed that the BACH1 919Ser polymorphism may be correlated with a
      decreased risk of breast cancer among Caucasian populations (Ser allele versus
      Pro allele: OR=0.90, 95% CI=0.86-0.95; Pro/Ser + Ser/Ser versus Pro/Pro: OR=0.90,
      95% CI=0.84-0.98; Ser/Ser versus Pro/Pro + Pro/Ser: OR=0.84, 95% CI=0.76-0.92;
      Ser/Ser versus Pro/Pro: OR=0.81, 95% CI=0.73-0.91; Ser/Ser versus Pro/Ser:
      OR=0.86, 95% CI=0.78-0.95), although not among Asian populations. Further
      subgroup analyses indicated that there were significant correlations between the
      BACH1 919Ser polymorphism and a decreased risk of breast cancer in postmenopausal
      females, females with a family history of breast cancer and females without
      BRCA1/2 mutations. Univariate and multivariate meta-regression analyses revealed
      that none of the factors explained the heterogeneity (all P>0.05). The present
      meta-analysis suggested that the BACH1 919Ser polymorphism may decrease the risk
      of breast cancer among Caucasian populations, particularly in postmenopausal
      females with a family history of breast cancer and without BRCA1/2 mutations.

PMID- 24137205
TI  - Splenic siderotic nodules in patients with liver cirrhosis.
AB  - The aim of this study was to investigate the interrelation between splenic
      siderotic nodules, hypersplenism and liver function in patients with liver
      cirrhosis. The splenic enhanced susceptibility-weighted angiography (ESWAN) and
      conventional magnetic resonance images of 33 patients with liver cirrhosis were
      retrospectively studied and the ESWAN images were graded. The distribution and
      prevalence of the image grades for patients with and without hypersplenism were
      evaluated. In addition, the splenic volume and the distribution of Child-Pugh and
      albumin scores were compared between patients with and without siderotic nodules,
      and the correlation between splenic volume and the ESWAN image grades were
      evaluated in the patients with siderotic nodules. The ESWAN images revealed
      splenic siderotic nodules in 24 patients. The distribution and prevalence of the
      ESWAN image grades were demonstrated to be significantly different (P<0.001)
      between patients with and without hypersplenism. Furthermore, significant
      differences were observed between patients with and without siderotic nodules
      with regard to splenic volume and the distribution of Child-Pugh and serum
      albumin scores (P<0.001). No significant correlation was demonstrated between
      splenic volume and the ESWAN image grades (P>0.05). In conclusion, a higher
      prevalence of splenic siderotic nodules (72.7%) was observed using the ESWAN
      sequence, in comparison with results from previous studies, obtained using the T1
      spoiled gradient echo sequence. The presence of splenic siderotic nodules was
      consistent with the occurrence of hypersplenism and was interrelated with
      reserved liver function.

PMID- 24137206
TI  - Extraction of polysaccharides from Fomes officinalis Ames and their antitumor
      activity.
AB  - The aim of this study was to optimize the extraction parameters of Fomes
      officinalis Ames polysaccharides (FOAPs) and evaluate their antitumor activity.
      FOAPs were extracted using the hot water extraction, acid extraction and alkali
      extraction methods, respectively. Alcohol precipitation and acetone washes were
      conducted to separate and purify the FOAPs. The FOAP content was determined using
      the phenol-sulfuric acid method. The effects of raw material particle size,
      extraction time and material-liquid ratio on the yield of FOAPs were
      investigated, and the effects of FOAPs on the immune function of S180 tumor
      bearing mice and their antitumor activity were evaluated. The yield of FOAPs
      obtained with the hot water extraction method was higher compared with the yields
      of the other methods. The optimum extraction conditions were as follows: a raw
      material particle size of 24 mesh; an extraction time of 2.5 h; and a material
      liquid ratio of 1 g:12 ml. Under these conditions, the yield of FOAPs was 1.13%.
      FOAPs significantly inhibited tumor growth and enhanced the immune function in
      S180 tumor-bearing mice. FOAPs extracted using the hot water extraction method
      have antitumor activity.

PMID- 24137207
TI  - Clinical value of a whole blood interferon-gamma release assay for the diagnosis
      of Mycobacterium tuberculosis infection during antitubercular treatment.
AB  - The aim of this study was to evaluate the sensitivity and specificity of a whole
      blood interferon-gamma release assay, the QuantiFERON(r)-TB Gold In-Tube (QFT
      GIT) test, in the diagnosis of Mycobacterium tuberculosis (MTB) infection, and to
      assess its monitoring role during antitubercular treatment. In total, 20 patients
      received the QFT test, along with other commonly-used tests, prior to, and
      following, 2- and 6-month courses of antitubercular treatment; the results were
      compared and statistically analyzed. The rate of positive results for
      tuberculosis (TB) was 95% for the QFT test, which was significantly higher
      compared with those for the purified protein derivative (PPD; 55%) and the
      antitubercular antibody tests (15%), as well as the acid-fast bacilli smear (20%)
      and cultures for TB (20%; P<0.05 for all). The sensitivity and specificity of the
      QFT test were 96 and 93.8%, respectively. The positive result rate obtained with
      the QFT test was significantly higher in the TB group compared with that in the
      non-TB group (6.3%; P<0.05). Moreover, the positive result rate obtained with the
      QFT test was significantly lower in the 6-month-treated group compared with that
      in the 2-month group (P<0.05). In conclusion, the QFT test is a sensitive and
      specific method for rapidly diagnosing MTB infection, and has an improved
      practical clinical value in evaluating antitubercular therapies compared with
      that of the PPD test.

PMID- 24137208
TI  - Substance P participates in immune-mediated hepatic injury induced by
      concanavalin A in mice and stimulates cytokine synthesis in Kupffer cells.
AB  - Studies have indicated that the immune system plays a pivotal role in hepatitis.
      Substance P (SP) has been shown to modulate the immune response. In order to
      investigate the role of SP in liver injury and to determine whether it leads to
      pro-inflammatory signaling, we established a mouse model of hepatic injury
      induced by concanavalin A (ConA). We also exposed mouse Kupffer cells (KCs) to SP
      in vitro. Cytokine and SP levels in liver homogenates were detected using enzyme
      linked immunosorbent assay (ELISA) and the protective effects of L-703,606 were
      evaluated through serological and histological assessments. Neurokinin-1 receptor
      (NK-1R) expression was evaluated by immunofluorescence and quantitative
      polymerase chain reaction (PCR). The levels of SP, alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) were significantly increased in the ConA
      treated mice and the levels of ALT and AST were markedly reduced by L-703,606
      pretreatment. Liver injury was significantly reduced by treatment with L-703,606.
      The mouse KCs expressed NK-1R and SP increased NK-1R mRNA expression.
      Furthermore, NK-1R blockade eliminated the effect of SP on NK-1R mRNA expression.
      The cytokine levels exhibited a substantial increase in the SP-pretreated KCs
      compared with the KCs that were cultured in control medium. The inter-leukin (IL)
      6 and tumor necrosis factor (TNF)-alpha levels in the L-703,606-pretreated KCs
      were significantly lower compared with those in the SP-pretreated KCs. Our study
      suggests that neurogenic inflammation induced by SP plays an important role in
      hepatitis. Mouse KCs express NK-1R and SP increases NK-1R mRNA expression. SP
      enhances IL-6 and TNF-alpha secretion and an NK-1R antagonist inhibits this
      secretion.

PMID- 24137209
TI  - Preventive effects of Lentinus edodes on homocysteinemia in mice.
AB  - Homocysteinemia is associated with cardiovascular and neuronal degenerative
      diseases. Deficiencies of the B vitamins lead to high homocysteine serum levels.
      Lentinus edodes (L. edodes) is also known as the Shiitake mushroom and may have
      beneficial effects on vascular and lipid metabolic diseases, including
      hypertension, homocysteinemia and lipidemia. In this study, we induced a
      homocysteinemia-like condition in mice by the administration of a folate- and
      vitamin B12-deficient diet and evaluated the effect of L. edodes on the
      homocysteinemia-like condition. Homocysteinemia was induced by the administration
      of a diet deficient in folate and vitamin B12 (DFV) for 6 weeks to mice aged 4-10
      weeks. The homocysteinemic mice were treated with L. edodes flour (5, 10 and
      20%), eritadenine (10 mg/kg) or DFV only (negative control) for 2 weeks. The DFV
      induced a significant increase in serum homocysteine levels. The increased
      homocysteine serum levels were reduced by eritadenine and L. edodes flour (5, 10
      and 20%). Hepatic levels of S-adenosyl-L-homocysteine hydrolase (SAH) were
      significantly higher under DFV administration and the elevated SAH levels were
      reduced by treatment with L. edodes in a dose-dependent manner. The mRNA
      expression levels of DNA methyl transferases, DNMT1 and DNMT3a, were reduced in
      the DFV group, and the reduced levels of DNMT1 and DNMT3a mRNA expression were
      recovered in the eritadenine and L. edodes (5, 10 and 20%) groups. These results
      suggest that components of L. edodes, including eritadenine may have beneficial
      effects on hyperhomocysteinemia and its therapeutic effects may be involved in
      the regulation of DNA methylation-related genes in mice.

PMID- 24137210
TI  - Pulmonary fat embolism and related effects during femoral intramedullary surgery:
      An experimental study in dogs.
AB  - The aim of the present study was to develop an animal model of pulmonary fat
      embolism (PFE) caused by femoral intramedullary procedures, and to investigate
      the initial changes in the hemodynamics, cytokines and risk factors of PFE.
      Sixteen dogs were randomly divided into two groups: Group A (intramedullary
      reaming and bone cement injection, n=8) and Group B (surgical approach without
      opening the medullary cavity, n=8). The hemodynamics, arterial blood gases and
      relevant cytokines were evaluated, and the lungs were examined using Oil Red O
      staining. In the animals of Group A, the heart rate, central venous pressure,
      mean pulmonary arterial pressure, pulmonary capillary wedge pressure and
      extravascular lung water (EVLW) were increased compared with the baseline levels,
      while the mean arterial pressure was decreased immediately following the reaming
      and bone cement infusion (P<0.05). Furthermore, there was a significant reduction
      in the pH and the arterial oxygen tension (PaO2), and a significant increase in
      the arterial carbon dioxide tension (PaCO2; P<0.05 for all) following the
      bilateral intramedullary surgery. The EVLW was correlated with the PaO2 (P<0.001)
      and PaCO2 (P=0.046). Following surgery, there was a significant increase in tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 levels
      in Group A (P<0.05). However, there were no significant changes in these
      parameters in Group B. The parameters tested, with the exception of pH, were
      significantly different in Group A compared with those in Group B (P<0.05)
      following the bilateral intramedullary surgery. Oil Red O staining was positive
      for all animals in Group A and negative for those in Group B. Femoral
      intramedullary surgery may induce PFE and subsequently affect hemodynamics and
      arterial blood gases. EVLW was correlated with the PaO2 (P<0.001) and the PaCO2
      (P=0.046). These results demonstrated that EVLW and cytokines may serve as
      predictors of the development of fat embolism syndrome (FES).

PMID- 24137211
TI  - Clinical value of multi-slice 3-dimensional computed tomographic angiography in
      the preoperative assessment of meningioma.
AB  - The aim of this study was to evaluate the clinical value of multislice 3
      dimensional computed tomographic angiography (3D-CTA) in the preoperative
      assessment of meningiomas. A total of 331 cases with meningiomas confirmed by CT
      and MRI were examined using 3D-CTA. The locations of the tumors were observed to
      be as follows: parasagittal and falcine in 125 cases, sphenoidal in 39 cases, in
      the olfactory groove in 19 cases, tentorial in 21 cases, parasellar in 33 cases,
      petroclival in 29 cases, intraventricular in 7 cases and on the convexity of the
      brain in 58 cases. The reconstructed images were processed by shaded volume
      rendering, maximum intensity projection and color-shaded surface display. The 3D
      CTA images were used to imitate the surgical approach. Surgery was performed
      according to the information provided in the 3D-CTA images. 3D-CTA provided clear
      3D images of the meningioma and the relationship with the adjacent vessels and
      the skull base, and demonstrated the optimal surgical approach for removing the
      neoplasm. The results of 3D-CTA corresponded extremely well with the surgical
      observations. 3D-CTA is able to provide 3D images of the meningioma, adjacent
      vessels and the bones in the skull base. Furthermore, 3D-CTA supplies information
      vital in the selection of the optimal surgical approach and information that aids
      the management of the sinus during the surgery. 3D-CTA is of great value in the
      preoperative evaluation of meningiomas.

PMID- 24137212
TI  - Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for
      the prevention of the no-reflow phenomenon following primary percutaneous
      coronary intervention in acute myocardial infarction.
AB  - Previous studies have shown that intracoronary (IC) nitroprusside (NTP) injection
      is a safe and effective strategy for the treatment of no-reflow (NR) during
      percutaneous coronary intervention (PCI). The present study tested the hypothesis
      that, on the basis of thrombus aspiration for the treatment of ST-segment
      elevation myocardial infarction (STEMI), the selective IC administration of a
      fixed dose of NTP (100 MUg) plus tirofiban is a safe and superior treatment
      method compared with the IC administration of tirofiban alone for the prevention
      of NR during primary PCI. A total of 162 consecutive patients with STEMI, who
      underwent primary PCI within 12 h of onset, were randomly assigned to two groups:
      Group A, IC administration of a fixed dose of NTP (100 MUg) plus tirofiban (10
      MUg/kg) and group B, IC administration of tirofiban (10 MUg/kg) alone (n=80 and
      n=82, respectively). The drugs were selectively injected into the infarct-related
      artery (IRA) via a thrombus aspiration catheter advanced into the IRA. The
      primary end-point was post-procedural corrected thrombolysis in myocardial
      infarction (TIMI) frame count (CTFC). The proportion of complete (>70%) ST
      segment resolution (STR); the TIMI myocardial perfusion grade (TMPG) 2-3 ratio
      following PCI; the peak value of creatine kinase (CK)-MB; the TIMI flow grade;
      the incidence of major adverse cardiac events (MACEs) and the left ventricular
      ejection fraction (LVEF) after 6 months of follow-up were observed as the
      secondary end-points. There were no significant differences in the baseline
      clinical and angiographic characteristics between the two groups. Compared with
      group B, group A had i) a lower CTFC (23+/-7 versus 29+/-11, P=0.000); ii) a
      higher proportion of complete STR (72.5 versus 55.9%, P=0.040); iii) an enhanced
      TMPG 2-3 ratio (71.3 versus 53.7%, P=0.030) and iv) a lower peak CK-MB value
      (170+/-56 versus 210+/-48 U/l, P=0.010). There were no statistically significant
      differences in the final TIMI grade-3 flow between the two groups (92.5 versus
      91.5% for groups A and B, respectively; P=0.956). The LVEF at 6 months was higher
      in group A than group B (63+/-9 versus 53+/-11%, respectively; P=0.001); however,
      the incidence of MACEs was not statistically different between the two groups,
      although there was a trend indicating improvement in group A (log rank
      chi2=0.953, P=0.489). The selective IC administration of a fixed dose of NTP (100
      MUg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA is a
      safe and superior treatment method compared with tirofiban alone in patients with
      STEMI undergoing primary PCI. This novel therapeutic strategy improves the
      myocardial level perfusion, in addition to reducing the infarct size.
      Furthermore, it may improve the postoperative clinical prognosis following PCI.

PMID- 24137213
TI  - A correlation analysis between the expression of pregnancy-associated plasma
      protein A in basal decidual cells and recurrent spontaneous abortion.
AB  - The aim of this study was to investigate the correlation between the expression
      of pregnancy-associated plasma protein A (PAPP-A) in basal decidual cells and
      recurrent spontaneous abortion (RSA). A total of 39 patients with a history of
      RSA were enrolled into the RSA group. A further 30 females who had experienced
      normal pregnancy were enrolled into the control group. The mRNA expression of
      PAPP-A in basal decidual cells was analyzed using real-time PCR. The distribution
      and expression of PAPP-A protein levels in basal decidual cells were analyzed by
      immunohistochemistry. The correlation between PAPP-A protein levels and RSA was
      analyzed. The levels of PAPP-A mRNA in the RSA group were significantly
      decreased, compared with the control group (P<0.05). Consistent with the mRNA
      levels, the protein levels of PAPP-A were also significantly lower in the RSA
      group compared with the control group (P<0.05). Multivariate logistic analysis
      indicated that the suppression of PAPP-A was one of the risk factors for RSA.
      Furthermore, Hosmer-Lemeshow analysis suggested that the expression levels of
      PAPP-A is an important factor for predicting RSA. In conclusion, the expression
      levels of the PAPP-A protein were significantly reduced in basal decidual cells
      of the RSA group compared with the control group. Therefore, PAPP-A is likely to
      play an important role in RSA.

PMID- 24137214
TI  - Meta-analysis of the therapeutic effects of various methods for the treatment of
      chronic atrial fibrillation.
AB  - The aim of this study was to analyze the therapeutic effects of various methods
      for the treatment of chronic atrial fibrillation (AF). Randomized controlled
      trials (RCT) concerning drug therapy and catheter ablation for the treatment of
      chronic AF were retrieved. The RevMan 5.1 software package was used for the meta
      analysis. A total of 20 papers were assessed in this study. The results of the
      analysis indicated that the success rate was lower [odds ratio (OR), 8.94; 95%
      confidence interval (CI), 4.70-17.02; P<0.0001] and the relapse rate was higher
      (OR, 0.07, 95% CI, 0.05-0.10; P<0.0001) for drug therapy compared with that for
      catheter ablation. With regard to different catheter ablation procedures, the
      success rate for pulmonary vein antrum isolation (PVAI) was lower compared with
      that for PVAI plus complex fractionated atrial electrogram (CFAE; OR, 0.53; 95%
      CI, 0.37-0.78; P=0.0001). Pulmonary vein isolation (PVI) plus left atrial
      ablation (LAA) had a higher success rate compared with PVI alone (OR, 2.79; 95%
      CI, 1.59-4.88, P=0.0003). There was not identified to be a significant difference
      in the success rates between PVAI and CFAE (OR, 2.05; 95% CI, 0.06-205.74;
      P=0.76) or between PVI and circumferential pulmonary vein isolation (CPVI; OR,
      0.94; 95% CI, 0.29-3.00; P=0.91). All the funnel plots of publication bias were
      essentially symmetrical. In conclusion, the success rate was higher and the
      relapse rate was lower for catheter ablation compared with drug therapy. Among
      the different procedures of catheter ablation, there were no significant
      differences in success rate between two single procedures; however, the success
      rates were higher for the combined methods compared with those for the single
      methods.

PMID- 24137215
TI  - Protective effect of dexmedetomidine in coronary artery bypass grafting surgery.
AB  - The aim of this study was to observe the impact of dexmedetomidine on
      postoperative myocardial injury in patients undergoing off-pump coronary artery
      bypass (OPCAB) grafting. One hundred and sixty-two patients who were undergoing
      OPCAB surgery were randomly divided into control and dexmedetomidine groups
      (groups C and Dex, respectively). Following the first vascular anastomosis
      grafting, the patients in group Dex received a continuous intravenous infusion of
      0.2-0.5 MUg/kg/h dexmedetomidine, until they were transferred to the Cardiac
      Surgery intensive care unit (ICU) for 12 h. Patients in group C received
      physiological saline intraoperatively and an intravenous infusion of 2-4 mg/kg/h
      isopropylphenol for postoperative sedation. Invasive arterial pressure and heart
      rate were continuously monitored for 5 min subsequent to entry into the operating
      theatre (T0), immediately following surgery (T1), 12 h post-surgery (T2), 24 h
      post-surgery(T3), 48 h post-surgery(T4) and 72 h post-surgery (T5). Blood samples
      were taken to determine the plasma levels of cardiac troponin I (cTnI) and
      creatine kinase-MB (CK-MB) at each time point. At 72 h post-surgery, a dynamic
      electrocardiogram was monitored. The blood pressure, heart rate, levels of cTnI,
      CK-MB, norepinephrine and cortisol, and postoperative arrhythmic events in the
      patients in group Dex all decreased compared with those in group C. The duration
      of mechanical ventilation and ICU residence time were also shorter than those in
      the control group (P<0.05). Dexmedetomidine reduced post-surgical myocardial
      injury in patients who had undergone OPCAB surgery.

PMID- 24137216
TI  - Influence of infection on the distribution patterns of NIH-Chronic Prostatitis
      Symptom Index scores in patients with chronic prostatitis/chronic pelvic pain
      syndrome (CP/CPPS).
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition
      for which the etiological determinants are still poorly defined. To better
      characterize the diagnostic and therapeutic profile of patients, an algorithm
      known as UPOINT was created, addressing six major phenotypic domains of CP/CPPS,
      specifically the urinary (U), psycho-social (P), organ-specific (O), infection
      (I), neurological/systemic (N) and muscular tenderness (T) domains. An additional
      sexual dysfunction domain may be included in the UPOINT(S) system. The impact of
      the infection domain on the severity of CP/CPPS symptoms is a controversial
      issue, due to the contradictory results of different trials. The aim of the
      present retrospective study was to further analyze the extent to which a positive
      infection domain of UPOINTS may modify the pattern of CP/CPPS symptom scores,
      assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index
      (NIH-CPSI). In a cohort of 935 patients that was divided on the basis of the
      presence or absence of prostatic infection, more severe clinical symptoms were
      shown by the patients with infection (median NIH total score: 24 versus 20 points
      in uninfected patients; P<0.001). Moreover, NIH-CPSI score distribution curves
      were shifted towards more severe symptoms in patients with a positive infection
      domain. Division of the patients into the six most prominent phenotypic clusters
      of UPOINTS revealed that the 'prostate infection-related sexual dysfunction'
      cluster, including the highest proportion of patients with evidence of infection
      (80%), scored the highest number of NIH-CPSI points among all the clusters. To
      assess the influence of the infection domain on the severity of patients'
      symptoms, all subjects with evidence of infection were withdrawn from the
      'prostate infection-related sexual dysfunction' cluster. This modified cluster
      showed symptom scores significantly less severe than the original cluster, and
      the CPSI values became comparable to the scores of the five other clusters, which
      were virtually devoid of patients with evidence of infection. These results
      suggest that the presence of pathogens in the prostate gland may significantly
      affect the clinical presentation of patients affected by CP/CPPS, and that the
      infection domain may be a determinant of the severity of CP/CPPS symptoms in
      clusters of patients phenotyped with the UPOINTS system. This evidence may convey
      considerable therapeutic implications.

PMID- 24137217
TI  - Astrocytoma development following complete multiple myeloma remission in a 49
      year-old patient: A case report.
AB  - Multiple myeloma (MM), one of the B-cell non-Hodgkin lymphomas, is a bone marrow
      derived, antibody-producing cancer of the plasma cells. In the advanced stages,
      the cancer cells frequently cause widespread osteolytic bone damage; however, in
      rare cases, MM also manifests as an intracranial plasmacytoma. In the present
      study, we describe a case in which a patient, initially treated for MM and with
      subsequent complete remission, was admitted to hospital with a lesion in the
      right cerebellar hemisphere and neurological symptoms of a brain tumor. Our
      initial diagnosis was an MM relapse with the rare occurring intracranial
      manifestation. However, pathological tests confirmed the diagnosis of a high
      grade astrocytoma. In this case report, we describe the characteristics, as well
      as the treatment issues, diagnoses and clinical developments of this patient.

PMID- 24137218
TI  - Biocompatibility study of a silk fibroin-chitosan scaffold with adipose tissue
      derived stem cells in vitro.
AB  - The use of tissue engineering technology in the repair of spinal cord injury
      (SCI) is a topic of current interest. The success of the repair of the SCI is
      directly affected by the selection of suitable seed cells and scaffold materials
      with an acceptable biocompatibility. In this study, adipose tissue-derived stem
      cells (ADSCs) were incorporated into a silk fibroin-chitosan scaffold (SFCS),
      which was constructed using a freeze-drying method, in order to assess the
      biocompatibility of the ADSCs and the SFCS and to provide a foundation for the
      use of tissue engineering technology in the repair of SCI. Following the seeding
      of the cells onto the scaffold, the adhesion characteristics of the ADSCs and the
      SFCS were assessed. A significant difference was observed between the
      experimental group (a composite of the ADSCs with the SFCS) and the control group
      (ADSCs without the scaffold) following a culture period of 6 h (P<0.05). The
      differences in the results at the following time-points were statistically
      insignificant (P>0.05). The use of an MTT assay to assess the proliferation of
      the cells on the scaffold revealed that there were significant differences
      between the experimental and control groups following culture periods of 2 and 4
      days (P<0.05). However, the results at the subsequent time-points were not
      statistically significantly different (P>0.05). Scanning electron microscopy
      (SEM), using hematoxylin and eosin (H&E) staining, was used to observe the
      cellular morphology following seeding, and this revealed that the cells displayed
      the desired morphology. The results indicate that ADSCs have a good
      biocompatibility with a SFCS and thus provide a foundation for further studies
      using tissue engineering methods for the repair of SCI.

PMID- 24137219
TI  - Isolation and characterization of serum albumin from Camelus dromedarius.
AB  - Serum albumin constitutes 35-50 mg/ml of plasma proteins and performs various
      physiological activities including the regulation of osmotic pressure on blood,
      maintaining buffering of the blood pH, carrying different fatty acids and other
      small molecules, such as bilirubin, hormones, drugs and metal ions, as well as
      participating in immunological responses. Serum albumin is an extensively used
      protein in biotechnological and pharmaceutical industries. The camel (Camelus
      dromedarius) is well tailored to successfully survive in extremely hot and dry
      climates. Plasma osmolality in the camel increases during water-deprived
      conditions. In such circumstances serum albumin is crucial in the regulation of
      blood pressure. The study of biochemical, biophysical and immunological aspects
      of camel serum albumin (CSA) are likely to provide molecular insights into camel
      physiology and may render it an alternative to human serum albumin (HSA) and
      bovine serum albumin (BSA) in all cases. However, these proteins are currently
      not available or cannot be utilized due to a variety of considerations. In this
      study, 12 mg of highly pure CSA was obtained from 1 ml plasma. Coomassie
      Brilliant Blue staining of SDS-PAGE yielded one band and RP-HPLC results revealed
      a single sharp peak, indicating homogenous preparation of the CSA. The
      charge/mass ratio and surface hydrophobicity of the CSA was similar to that of
      BSA. Mass spectrometry analysis of the purified protein confirmed the identity of
      CSA.

PMID- 24137220
TI  - Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta
      analysis.
AB  - This meta-analysis was performed to evaluate the efficacy and safety of parecoxib
      sodium for acute postoperative pain. PubMed, Cochrane Central Register of
      Controlled Trials, EBSCO, Springer, Ovid and Chinese National Knowledge
      Infrastructure (CNKI) databases were searched from January 1999 to January 2013
      to comprehensively collect randomized controlled trials (RCTs) of parecoxib
      sodium for acute postoperative pain. The methodological quality of the included
      RCTs were assessed and the data were extracted by two reviewers independently
      according to the Cochrane Handbook. Efficacies and safety (respiratory
      depression, pruritus, fever, headache, and nausea and vomiting) were pooled using
      meta-analysis performed by Review Manager 5.1 software. Relative risk (RR) and
      95% confidence interval (CI) were calculated in a fixed-effects model. Seven RCTs
      involving 1,939 patients met the inclusion criteria. The results of the meta
      analysis revealed that the rate of 'effective' treatment as described by the
      patients' global evaluation of study medication (PGESM) was higher in the patient
      controlled analgesia (PCA) combined with parecoxib sodium group 24, 48, and 72 h
      after the initial intravenous dose of 40 mg parecoxib compared with that in the
      control group [PCA alone; RR=1.41, 95% CI (1.13-1.75); RR=1.25, 95% CI (1.15
      1.35); and RR=1.30, 95% CI (1.21-1.40), respectively]. The rate of 'ineffective'
      treatment in the PCA combined with parecoxib sodium group was lower compared with
      that of the control group [RR=0.43, 95% CI (0.26-0.72); RR= 0.44, 95% CI (0.34
      0.57); and RR= 0.33, 95% CI (0.23-0.48), respectively]. Combination of PCA with
      parecoxib sodium reduced the incidence of postoperative fever [RR=0.34, 95% CI
      (0.22-0.53)], as well as nausea and vomiting [RR=0.69, 95% CI (0.57-0.83)];
      however, it did not significantly reduce respiratory depression [RR= 0.84, 95% CI
      (0.38-1.83)], pruritus [RR= 0.91, 95% CI (0.54-1.52)] or headache [RR=0.77, 95%
      CI (0.47-1.28)]. The combination of PCA with parecoxib sodium successively
      injected for <3 days significantly increases the scores of PGESM and reduces the
      incidence of adverse effects and postoperative complications.

PMID- 24137221
TI  - Correlation between the microinflammatory state and left ventricular structural
      and functional changes in maintenance haemodialysis patients.
AB  - The aim of this study was to examine the correlation between the
      microinflammatory state and structural and functional changes of the left
      ventricle in maintenance haemodialysis patients (MHD). In total, 48 MHD patients
      and 30 healthy volunteers participated in this study. The microinflammatory state
      was detected from high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL
      6) and tumour necrosis factor-alpha (TNF-alpha) levels determined by ELISA. The
      structure and function of the left ventricle was measured according to ultrasound
      cardiogram examination. The serum levels of hs-CRP, IL-6 and TNF-alpha in the MHD
      patients were higher compared with those in the controls (P<0.05). Furthermore,
      the measurements of the left atrial diameter (LAD), left venticular diameter
      (LVD), interventricular septal thickness (IVST), left ventricular posterior wall
      thickness (LVPWT) and the left ventricular mass index (LVMI) increased
      significantly and the left ventricular function (LVEF) was reduced. Correlation
      analysis demonstrated that the concentrations of hs-CRP, TNF-alpha and IL-6
      correlated with the LVMI (P<0.05), but only hs-CRP correlated with the loss of
      function of the heart in the haemodialysis patients (P<0.05). The
      microinflammatory state may be closely associated with the structural and
      functional impairment of the heart in MHD patients.

PMID- 24137222
TI  - Correlation between fungal sIgE and bronchial asthma severity.
AB  - Fungal sensitisation is closely associated with asthma; however, the correlation
      between fungi and asthma severity remains unclear. The aim of this study was to
      investigate the severity of asthma in 100 patients with asthma due to fungal and
      non-fungal allergens. A total of 100 outpatients and inpatients with asthma were
      selected from 2010 to 2011 and were divided into three groups (mild, moderate and
      severe) according to their clinical manifestations, lung function results and
      treatment situations. Enzyme-linked immunosorbent assay (ELISA) was used to
      detect the levels of specific immunoglobulin E (sIgE) to five fungal allergens
      and seven non-fungal allergens in the serum of all patients. The levels of sIgE
      to Aspergillus, Penicillium and Candida albicans allergens in the severe group
      were significantly higher compared with those in the moderate and mild groups
      (P<0.001 and P<0.05, respectively); those of the moderate group were
      significantly higher compared with those of the mild group (P<0.05). No
      significant difference was observed for the levels of sIgE to Alternaria
      alternata among the three groups. sIgE to Cladosporium herbarum was not present
      for all three groups. No significant difference was observed for the levels of
      sIgE to non-fungal allergens among the three groups. Fungal allergens are closely
      correlated with the severity of asthma, whereas non-fungal allergens are not.

PMID- 24137223
TI  - Quality of life in women with female pattern hair loss and the impact of topical
      minoxidil treatment on quality of life in these patients.
AB  - Female pattern hair loss (FPHL) is the most common hair loss disorder in women
      and it may impact on the psychological and social activities of patients, thereby
      reducing their quality of life (QoL). Topical minoxidil has been shown to be
      effective and safe in the treatment of patients with FPHL. The aim of this study
      was to assess the QoL of patients with FPHL and investigate whether topical
      minoxidil solution treatment improves the QoL of these patients. In this study,
      we enrolled 125 female patients aged 16-72 years to answer visual analog scale
      (VAS) and dermatology life quality index (DLQI) questionnaires. Of these
      patients, 31 were recruited for the follow-up study after 12 months of treatment
      with 2% minoxidil. Each index and the change in QoL prior to and following
      treatment were statistically analyzed. There was identified to be a correlation
      between clinical severity and the values of the indices in all patients. There
      was a statistically significant difference between the VAS and DLQI scores prior
      to and following treatment with 2% minoxidil. A comparison between the good
      responders (n=23) and the poor responders (n=8) revealed no significant
      difference in the improvement of VAS and DLQI scores. The QoL of the patients was
      severely impaired by FPHL. The DLQI and VAS used in this study were validated as
      useful indices for the evaluation of QoL due to their high reliability,
      sensitivity and simplicity. This evaluation is recommended for the management of
      FPHL treatment. The results of the study demonstrated that topical minoxidil
      improved the QoL of the patients.

PMID- 24137224
TI  - Characterization of beta-cell function and insulin resistance in overweight
      Chinese adolescents with normal glucose tolerance.
AB  - This study aimed to investigate the characteristics of insulin resistance and
      beta-cell secretion in healthy adolescents. A total of 124 adolescents with
      normal glucose tolerance (NGT) were divided according to BMI into normal weight
      (n=31; control), overweight (n=52) and obese (n=41) groups. Oral glucose
      tolerance tests were performed, and blood glucose (G0, G30 and G120) and insulin
      (I0, I30 and I120) levels at 0, 30 and 120 min, respectively, were measured. The
      homeostasis model assessment estimate of insulin resistance (HOMA-IR) and early
      insulin release index (IRI) were calculated to evaluate insulin sensitivity and
      early beta-cell secretion. The G0, G120 levels and the natural logarithm (Ln) of
      I30 and DeltaI30/DeltaG30 were similar in the overweight and obese groups, but
      significantly higher compared with those of the normal weight group (P<0.05).
      LnI0 and LnHOMA-IR progressively increased (P<0.01) in correlation with the
      degree of obesity among the three groups. LnDeltaI30/DeltaG30 and LnHOMA-IR were
      significantly positively correlated with the indices of obesity (P<0.001 and
      P<0.05, respectively). LnHOMA-IR was also positively correlated with the insulin
      levels at 30 and 120 min (r=0.454 and 0.314, respectively; P<0.001). In healthy
      adolescents, insulin resistance progressively increased with increased body mass
      index (BMI), but the compensatory increase in early insulin secretion was
      limited.

PMID- 24137225
TI  - Construction and expression of D-dimer and GPIIb/IIIa single-chain bispecific
      antibody.
AB  - The aim of this study was to construct a plasmid expressing glycoprotein IIb-IIIa
      (GPIIb/IIIa) and D-dimer single-chain bispecific antibody for the targeted
      therapy of thrombosis. The phosphorylated gene encoding the anti-GPIIb/IIIa
      single-chain variable fragment (scFv) and the gene encoding the anti-D-dimer scFv
      were amplified by PCR and linked in tandem by blunt-end ligation. The recombinant
      plasmid was transfected into the competent cell line HB2151 and identified by PCR
      and DNA sequencing. Then, the soluble recombinant antibody in bacterial lysates
      was purified by an NTA column and molecular sieve chromatography in turn.
      Finally, the binding specificity of the purified antibody was tested by enzyme
      linked immunosorbent assay (ELISA). Results demonstrated that the construction of
      the expression plasmid was successful and the purified recombinant protein, which
      had a molecular weight of ~56 kDa, was specific to GPIIb/IIIa and D-dimer. In
      conclusion, a plasmid expressing a bispecific antibody was constructed by a new
      method of blunt-end ligation. The soluble recombinant protein is a promising
      platform for target-oriented thrombolytic therapy.

PMID- 24137226
TI  - Combination treatment with asiaticoside and rapamycin: A new hope for in-stent
      restenosis.
AB  - The aim of this study was to investigate and characterize the efficacy and
      mechanism of action of asiaticoside in combination with rapamycin in the
      inhibition of in-stent restenosis (ISR). The effects of asiaticoside combined
      with rapamycin on cell proliferation in vitro were evaluated by MTT assay. The
      mRNA expression was analyzed by quantitative polymerase chain reaction (qPCR).
      Enzyme-linked immunosorbent assay (ELISA) was used to confirm protein synthesis.
      The cell growth inhibition rate in the combination group was significantly higher
      compared with those in the asiaticoside and rapamycin groups for human aortic
      fibroblasts (HAFs; 63.50+/-3.83, 53.06+/-8.10 and 60.34+/-4.9%, respectively) and
      human aortic smooth muscle cells (HASMCs; 33.12+/-1.35, 26.21+/-7.59 and 28.27+/
      4.92, respectively; P<0.05). However, for human coronary artery endothelial cells
      (HCAECs), the cell growth inhibition rates in the combination, asiaticoside and
      rapamycin groups were 11.09+/-1.17, 26.22+/-4.24 and 34.80+/-2.80%, respectively
      (P<0.05), as detected by MTT assay. The qPCR assay showed that in the combination
      group the level of von Willebrand factor (vWF) mRNA was downregulated, while
      platelet endothelial cell adhesion molecule (PECAM-1) and endothelial nitric
      oxide synthase (eNOS) mRNAs were upregulated in HCAECs compared with the
      rapamycin group (P<0.05). Transforming growth factor (TGF)-beta1 and TIMP1 mRNAs
      were downregulated while Smad7 and matrix metalloproteinase 1 (MMP1) mRNAs were
      upregulated in HAFs compared with the rapamycin and AT groups (P<0.05). The ELISA
      showed that the type I collagen level was significantly reduced in HASMCs and
      HAFs (P<0.05). The data suggest that asiaticoside combined with rapamycin may be
      effective in the reduction of ISR.

PMID- 24137227
TI  - Gardenia oil increases estradiol levels and bone material density by a mechanism
      associated with upregulation of COX-2 expression in an ovariectomized rat model.
AB  - This study aimed to determine the effects and mechanisms of gardenia oil on bone
      density and bone biomechanics in ovariectomized female rats. An ovariectomized
      rat model was established and the rats were administered various doses of
      gardenia oil. Rats administered diethylstilbestrol or saline served as the
      positive and the untreated controls, respectively. All rats received the same
      surgery, with the exception of the ovariectomy in the sham group. The levels of
      serum 17beta-estradiol, follicle-stimulating hormone, luteinizing hormone,
      alkaline phosphatase (ALP) and calcium, and the bone material density (BMD),
      maximum stress and maximum strain were determined. The expression of COX-2 was
      also determined by immunoblotting and quantitative PCR (qPCR). Gardenia oil
      increased the serum levels of 17beta-estradiol, the BMD, and the maximum stress
      and maximum strain of bones. The levels of COX-2 protein and COX-2 mRNA were
      significantly increased in the gardenia oil-treated rats. In conclusion, gardenia
      oil increases estradiol levels and BMD in an ovariectomized rat model. The
      effects of gardenia oil are associated with upregulation of the expression of COX
      2.

PMID- 24137228
TI  - Carbamylated erythropoietin attenuates cardiomyopathy via PI3K/Akt activation in
      rats with diabetic cardiomyopathy.
AB  - The aim of the present study was to investigate the protective effect of
      carbamylated erythropoietin (CEPO) against cardiomyopathy in high-fat, high
      carbohydrate diet-fed rats with streptozotocin (STZ)-induced diabetic
      cardiomyopathy (DCM). Healthy male Wistar rats were fed a high-fat, high
      carbohydrate diet for four weeks, and then were injected with STZ twice (50
      mg/kg, intraperitoneally). Once DCM was confirmed, the rats were divided randomly
      into the following groups: DCM without treatment, CEPO treatment at different
      dosages (500, 1,000 or 2,000 IU/kg) or recombinant human erythropoietin (rhEPO)
      treatment (1,000 IU/kg), for a four-week short intervention or an eight-week long
      intervention protocol. Healthy rats were used as normal controls. Venous blood
      samples were drawn for routine hematological examinations, and heart tissues were
      collected for histological analysis, as well as the determination of myocardial
      apoptosis and phosphatidylinositol-3-kinase (PI3K)/Akt signaling. CEPO treatment
      had no significant effect on the erythrocyte or hemoglobin levels in the rats
      with DCM; however, it reduced myocardial cell apoptosis in the rats and protected
      the cellular ultrastructure. In addition, CEPO treatment inhibited caspase-3 and
      increased Bcl-xl protein expression (P<0.05). It also increased PI3K (p85) and
      Akt1 expression at the mRNA and protein levels in the hearts of the rats with
      DCM, with a dose-response relationship. An eight-week treatment using CEPO, in
      comparison with a four-week protocol, marginally increased PI3K (p85) and Akt1
      expression, and did not demonstrate significant benefit. The study indicated that
      CEPO protects against DCM, without markedly affecting erythropoiesis, and that
      the activation of PI3K/Akt may be a key mechanism in the protection conferred by
      CEPO.

PMID- 24137229
TI  - Induction of apoptosis in infantile hemangioma endothelial cells by propranolol.
AB  - Propranolol, a non-selective beta-blocker, is emerging as an effective treatment
      for complicated hemangiomas. The aim of this study was to investigate the
      molecular mechanism(s) underlying the therapeutic effects of propranolol against
      hemangiomas, using primary infantile hemangioma endothelial cells (IHECs). IHECs
      were treated with various concentrations of propranolol and morphological changes
      and apoptosis were assessed. Changes in the expression levels of apoptosis
      related genes were examined. Annexin-V staining revealed that propranolol at 40,
      50 and 60 MUg/ml caused a concentration-dependent increase in the apoptosis of
      IHECs. Morphological analyses revealed that exposure to 50 MUg/ml propranolol
      resulted in typical apoptotic changes, including shrinkage, the formation of
      apoptotic bodies and retention of plasma membrane integrity. Gene expression
      analyses revealed that propranolol treatment led to a marked increase in the
      expression of caspase-8, cytochrome c, apoptosis-inducing factor, caspase-3 and
      poly (ADP-ribose) polymerase 1, as well as a concomitant reduction in lamin B1
      expression. Our data collectively demonstrate that propranolol induces apoptosis
      of IHECs through activation of the intrinsic and extrinsic apoptotic pathways,
      which represents an important mechanism for its therapeutic effects against
      infantile hemangiomas.

PMID- 24137230
TI  - Treatment of recurrent mandibular ameloblastoma.
AB  - Ameloblastoma is a locally invasive benign odontogenic tumor with a high rate of
      recurrence in the long term. The authors conducted a retrospective study of
      patients with mandibular ameloblastoma in order to evaluate recurrent
      ameloblastoma management. The study included data from 31 patients over a period
      of 10 years. Data collected included age, gender, tumor location, histological
      findings, initial treatment, number of recurrences and year of onset, type of
      treatment of recurrence, reconstruction and follow-up. Recurrences were detected
      in nine patients (29%). Tumor recurrences appeared at 32 months on average
      following the initial surgical procedure. Recurrences were associated mainly to
      inadequate initial therapeutic approach and were treated by bone resection with a
      safety margin of at least 1 cm beyond the radiographically visible margins.
      Immediate reconstruction of bone defects was performed with grafts or free flaps.

PMID- 24137231
TI  - A study on the position and etiology of infection in cirrhotic patients: A
      potential precipitating factor contributing to hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a severe and high-mortality complication in
      cirrhotic patients. In this study, we analyzed infection, one of the common
      precipitating factors of HE in patients with cirrhosis, in order to identify
      common infection sites and the etiology. In addition, we aimed to identify
      information useful in the early prevention and effective treatment of HE. Ninety
      two patients presenting with hepatitis B virus-related cirrhosis with HE (HBC-HE)
      and 45 patients presenting with alcoholic cirrhosis with HE (ALD-HE) were
      enrolled in this study. We collected and analyzed data concerning the
      precipitating factors of HE using blood tests, biochemical detection and
      bacterial culture to identify which precipitating factor was the most common.
      Fifty-three patients with HE (37 with HBC-HE and 16 with HBC-HE) had infection as
      the precipitating factor. These infections included respiratory tract infection
      (56.6%), intestinal tract infection (20.7%), peritoneal infection (17.0%) and
      urinary tract infection (5.7%). The white blood cell (WBC) counts increased in 17
      cases (32.1%) and neutrophil (NEUT) numbers increased in 39 cases (73.6%), while
      WBC counts were lower in the patients with respiratory tract infection compared
      with those in the patients with infections at other sites (P<0.05). The levels of
      plasma ammonia were significantly higher in patients with intestinal tract
      infection than in those with other sites of infection (P<0.05). The proportions
      of patients with hyperammonemia, increased NEUT numbers, hyponatremia and low
      albumin were higher in the infection group compared with those in the non
      infection group (P<0.05). Pneumococci and E. coli were common bacteria that
      induced infection in the respiratory tract and at other infection sites,
      respectively. Respiratory tract infection was identified to be the most common
      precipitating factor for HE.

PMID- 24137232
TI  - Clinical effectiveness of the PolyScopeTM endoscope system combined with holmium
      laser lithotripsy in the treatment of upper urinary calculi with a diameter of
      less than 2 cm.
AB  - The aim of this study was to evaluate the clinical value of the PolyScopeTM
      endoscope system in the treatment of upper urinary calculi with a diameter of <2
      cm. A total of 86 patients hospitalized with upper urinary tract calculi were
      included. The patients were placed under general or spinal anesthesia and in a
      lithotomy position. Following the dilation of the ureter, a guide wire was
      inserted under the direct vision of an F8/9.8 rigid ureteroscope, and an F12/14
      flexible ureteral access sheath was positioned along the guide wire. Holmium
      laser lithotripsy was subsequently performed, using an F8.0 'PolyScope' modular
      flexible ureteroscope. Plain film of the kidney-ureter-bladder (KUB) was
      performed 1 day subsequent to the surgery, in order to determine the result of
      the lithotripsy and the position of the double-J stent which was inserted after
      after holmium laser lithotripsy. In addition, in certain patients, KUB
      radiography was performed 2-4 weeks subsequent to the surgery, and extracorporeal
      shockwave lithotripsy (ESWL) was performed if the diameter of the residual stones
      was >6 mm. Lithotripsy was successful in 77 patients and the duration of the
      surgery ranged between 25 and 80 min (mean duration, 42 min). Little bleeding was
      observed. Three patients presented with a slight fever following the surgery;
      however, no ureteral perforation, high fever or septicemia was observed among the
      patients following anti-inflammatory treatment. The stone-free rate (SFR) of the
      single-pass lithotripsy was 89.5% (77/86) and the SFR with ESWL was 96.5%
      (83/86). The study demonstrated that the F8 modular flexible ureteroscope was
      safe, convenient and effective for the lithotripsy of upper-tract calculi.

PMID- 24137233
TI  - Application of lamina replantation with ARCH plate fixation in thoracic and
      lumbar intraspinal tumors.
AB  - The aim of the present study was to investigate the clinical effects of lamina
      replantation with ARCH plate fixation on patients with thoracic and lumbar
      intraspinal tumors, following laminectomy. Thirteen patients with thoracic and
      lumbar intraspinal tumors underwent total lamina replantation with ARCH plate
      fixation and repair of the supraspinous ligaments, following laminectomy and
      tumor enucleation. To investigate the clinical effect of lamina replantation with
      ARCH plate fixation, pre- and postoperative visual analog scale (VAS), and
      Oswestry Disability Index (ODI) scores were determined, and pre- and
      postoperative X-ray and magnetic resonance imaging (MRI) examinations were
      conducted. Computed tomography (CT) examinations were also included in the follow
      up. No complications were observed pre- or postoperatively. The VAS and ODI
      results 2 weeks following surgery and at the final follow-up examination
      demonstrated a significant improvement compared with the corresponding
      preoperative results. The X-ray examination results indicated a satisfactory
      internal fixation location, without any characteristics of a fracture, lumbar
      scoliosis, kyphosis or instability. Following the surgery, the CT and MRI
      examination results demonstrated that healing of the lamina bone and repair of
      the supraspinous ligament had occurred without tumor recurrence or spinal
      epidural scar recompression. Two of the 13 cases were lost to follow-up. The
      results indicated that in patients with thoracic and lumbar intraspinal tumors,
      lamina replantation with ARCH plate fixation following total laminectomy is
      effective and provides thoracolumbar stability. Furthermore, this has been
      identified to be an effective technique for preventing intraspinal scar
      proliferation.

PMID- 24137234
TI  - Sedative effects of Arachis hypogaea L. stem and leaf extracts on sleep-deprived
      rats.
AB  - Arachis hypogaea L. stem and leaf extracts (AHSLE) are reputed to aid sleep. The
      purpose of this study was to evaluate the sedative effects of AHSLE on sleep
      deprived (SD) rats and the effect on energy system pathways. Furthermore, we
      analyzed the essential oil components of Arachis hypogaea L. stems and leaves
      (AHSL) to explain the sedative effects. AHSLE were obtained by extracting AHSL
      twice with water at 98 degrees C for 3 h. Animal experiments were performed in
      the Laboratory Animal Resource Center, University of Tsukuba, Japan, and the
      levels of neurotransmitters were analyzed by high performance liquid
      chromatography (HPLC). The essential oil of the AHSL was obtained by simultaneous
      distillation and extraction (SDE) and analyzed by gas chromatography-mass
      spectrometry (GC-MS). Following treatment with AHSLE, the adenosine triphosphate
      (ATP) levels of the SD rats increased, which is a different effect from that
      previously observed in freely behaving rats. Adenosine (Ad) were not elevated by
      AHSLE uniformly throughout the brain, but accumulated in site-specific and time
      prolonged manners. Following GC-MS analysis of the AHSL essential oil, a total of
      37 compounds were identified; the major components were linalool (16.17%, which
      has sedative-like activity), n-hexadecanoic acid (16.42%), and 1-octen-3-ol
      (8.48%; a product of linalool decomposition). AHSLE affect the target
      neurotransmitters related to the rat circadian rhythms in specific brain regions,
      suggesting that AHSLE have the potential to increase sleep during the SD phase,
      and the sedative effects of AHSLE may be due to high levels of linalool and its
      decomposition products. AHSLE are potentially useful as sedatives or sleep aids
      in hypnotic therapy.

PMID- 24137235
TI  - Oblique coronal view of the ACL double-bundle: Comparison of the Chinese Visible
      Human dataset and low-field MRI.
AB  - The aim of this study was to distinguish the individual bundles of the anterior
      cruciate ligament (ACL) using the Chinese Visible Human (CVH) dataset and images
      obtained by low-field routine magnetic resonance imaging (MRI) in the oblique and
      coronal planes. Sectional anatomical data of the knee were selected from the CVH
      dataset and reconstructed in 3D. MRI of normal knees was performed with a low
      field-strength magnet in the coronal plane. The shape of the ACL was clearly
      displayed. Using the oblique coronal plane, the anteromedial (AM) and
      posterolateral (PL) bundles of the ACL were distinguished in the reconstructed
      anatomical data and the MR images. The double-bundle structure of the ACL was
      evaluated in the CVH 3D reconstructions and MR images. Using the oblique coronal
      plane, it was possible to review the ACL structure in the knee. The study
      demonstrated the feasibility of distinguishing the two bundles in the ACL with
      CVH 3D reconstruction and low-field strength MRI. The accuracy in the grading of
      ACL injury in presurgical planning may be improved.

PMID- 24137236
TI  - Reduction of leptin levels by four cardiac hormones: Implications for
      hypertension in obesity.
AB  - Circulating levels of leptin are increased in obesity and have been proposed to
      contribute to the development of hypertension in obese individuals. Four cardiac
      hormones, specifically, vessel dilator, long-acting natriuretic peptide (LANP),
      kaliuretic peptide and atrial natriuretic peptide (ANP), have blood pressure
      lowering properties and correlate with the presence of hypertension in obesity.
      The objective of this study was to determine whether one or more of these cardiac
      hormones was able to decrease the levels of leptin in the hypothalamus, an area
      of the brain that has been demonstrated to synthesize more than 40% of leptin in
      the circulation. The effects of these four cardiac hormones on leptin were
      examined using dose-response curves in the rat hypothalamus, which synthesizes
      leptin. Vessel dilator, LANP, kaliuretic peptide and ANP maximally decreased the
      levels of leptin in hypothalamic cells by 79, 76, 80 and 62%, respectively
      (P<0.0001 for each). The cardiac hormones decreased leptin levels over a
      concentration range of 100 pM to 10 MUM, with the most significant reductions in
      leptin levels occurring when the concentrations of the hormones were at
      micromolar levels. The results of the study suggest that the four cardiac
      hormones lead to significant reductions in hypothalamic leptin levels, which may
      be an important mechanism for alleviating leptin-induced hypertension in obesity.

PMID- 24137237
TI  - Possible primary immunodeficiency presenting with gastrointestinal symptoms: Case
      report and minireview.
AB  - Primary immunodeficiency is a disease characterized by reduced levels of serum
      immunoglobulins and multiple clinical manifestations. Patients with primary
      immunodeficiency frequently present with gastrointestinal symptoms, such as
      diarrhea, malabsorption and weight loss. The mainstay of treatment is replacement
      therapy with intravenous immunoglobulin (IVIG). In the current study, we report
      the case of a 23-year-old man with symptoms of chronic diarrhea, malabsorption
      and weight loss that had been apparent for two years. Subsequent to being
      diagnosed with possible primary immunodeficiency, the patient was treated with 30
      mg/day oral prednisone for one month. The prednisone was then tapered weekly by 5
      mg until withdrawal. Three months later, the patient's clinical symptoms
      disappeared and his quality of life improved. During the subsequent nine months
      follow-up, the patient was able to work without suffering any effects from his
      illness. The body weight of the patient increased and plasma albumin levels were
      normal. In conclusion, this study describes the case of a patient with primary
      immunodeficiency-related gastrointestinal symptoms who responded well to oral
      prednisone treatment.

PMID- 24137238
TI  - N-methyl-N-nitrosourea-induced cerebellar hypoplasia in rats: Effect of
      arachidonic acid supplementation during the gestational, lactational and post
      weaning periods.
AB  - Arachidonic acid (AA) is a fatty acid that is important for visual and brain
      development and is commonly added as a functional food ingredient to commercial
      infant formulas worldwide. However, few studies have examined whether AA
      supplementation during neonatal life has an effect on neuronal abnormalities. In
      the present study, the effect of dietary AA supplementation in dams during
      gestation and lactation was investigated by examining N-methyl-N-nitrosourea
      (MNU)-induced cerebellar hypoplasia in young Lewis rats. Dams were fed a 2.0% AA
      diet or a basal diet (<0.01% AA). At birth (postnatal day 0), male and female
      pups received a single intraperitoneal injection of 35 mg/kg MNU or vehicle.
      Brain weights were measured and a morphological analysis of macroscopic and
      histological specimens was conducted after 7, 14, 21, 28 and 60 days.
      Irrespective of whether the rats had been fed an AA diet, the brain weights of
      the MNU-treated rats, particularly the weights of the cerebellum, were decreased
      compared with those of the MNU-untreated rats from the 14th day following the MNU
      injection. Macroscopic reductions in the cerebellar length and/or width and
      histologically observed reductions in cerebellar vertex height and/or cortex
      width were also detected in the MNU-treated rats, irrespective of whether the
      rats had been fed with AA. Histopathologically, the MNU-treated rats
      (irrespective of AA supplementation) exhibited disorganization of the cerebellar
      cortex and disarrangement of the cortical layers (loss and/or disturbance of the
      molecular, Purkinje and granular cell layers). There were no significant
      differences in any parameters among the MNU-treated rats, irrespective of whether
      the rats had been fed an AA diet. In conclusion, an AA-rich diet for dams during
      gestation and lactation did not modify MNU-induced cerebellar hypoplasia in their
      offspring.

PMID- 24137239
TI  - Expression and activity of the TLR4/NF-kappaB signaling pathway in mouse
      intestine following administration of a short-term high-fat diet.
AB  - Insulin resistance in obesity is associated with chronic systemic low-grade
      inflammation. Although it has been shown that Toll-like receptor 4 (TLR4) in the
      liver, muscle and adipose tissue plays an important role in obesity-associated
      inflammation and insulin resistance, the effect of TLR4 activation in the
      intestine has not been investigated. The aim of this study was to explore the
      activation of the mouse intestinal TLR4/NF-kappaB signaling pathway following the
      administration of a short-term high-fat diet, as well as the function of the
      signaling pathway in the local enteric inflammatory response. The effect of the
      high-fat diet on TLR4 activation, NF-kappaB and phosphorylated IkappaB (PIkappaB)
      activity, and tumor necrosis factor (TNF)-alpha and IL-6 expression in the
      intestinal tissues of diet-induced obese C57BL/6 mice was investigated. The
      results demonstrated that the high-fat diet induced TLR4 mRNA and protein
      expression in intestinal tissues. TLR4/NF-kappaB signaling pathway activation
      gradually increased as the number of days of high-fat diet administration
      increased, and peaked on day 7. Additionally, activation of the signaling pathway
      reduced PIkappaB expression levels and increased TNF-alpha and IL-6 expression
      levels in intestinal tissues. Our results demonstrated that a short-term high-fat
      diet induces activation of the TLR4/NF-kappaB signaling pathway in intestinal
      tissues, which causes local intestinal low-grade inflammation. These data improve
      our understanding of the molecular events involved in intestinal low-grade
      inflammation, which may be the triggering factor for chronic systemic low-grade
      inflammation.

PMID- 24137240
TI  - Combination of ketamine and xylazine exacerbates cardiac dysfunction in severely
      scalded rats during the shock stage.
AB  - Cardiac inhibition due to burn injury and anesthetics have been documented
      previously. However, little is known about their combined effects on cardiac
      function. The aim of the present study was to observe the effects of a
      ketamine/xylazine (K/X) combination on the cardiac function of rats with severe
      scalds and compare them with those of avertin. Adult rats were randomly
      distributed into four groups: the KXB group (scalds anesthetized with K/X, n=10),
      the KXC group (sham scalds anesthetized with K/X, n=10), the AVB group (scalds
      anesthetized with avertin, n=10) and the AVC group (sham scalds anesthetized with
      avertin, n=10). Ketamine and xylazine were administered at 25 and 6 mg/kg,
      respectively, and avertin at 200 mg/kg before full-thickness scalds or sham
      scalds of 30% total body surface area (TBSA) were produced. Echocardiographic
      parameters were assessed following injury. The heart rate (HR) in the KXB group
      was fatally low during the study period. Fractional shortening (FS%) and ejection
      fraction (EF) in the KXB group were extremely low initially and remained low. The
      left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic
      volume (LVESV) were reduced in the burned rats. Serum levels of cardiac troponin
      I (cTnI) were significantly higher in the KXB group than in the AVB group (1.66+/
      0.28 vs. 1.16+/-0.34 ng/ml, P<0.01). The highest lung wet/dry weight ratio was
      observed in the KXB group. However, no evident heart tissue pathological changes
      were observed in these groups. The apoptotic index of myocardial cells and
      caspase 3 expression level were highest in the KXB group (P<0.01). In conclusion,
      K/X exacerbated cardiac inhibition in severely scalded rats during the shock
      stage by a mechanism which may involve mitochondrial apoptosis.

PMID- 24137241
TI  - Triptolide markedly attenuates albuminuria and podocyte injury in an animal model
      of diabetic nephropathy.
AB  - Triptolide is a major active component of Tripterygium wilfordii Hook F, which
      exerts marked immunosuppressive, anti-inflammatory and podocyte-protective
      effects. In this study, the ability of triptolide to inhibit inflammation and
      attenuate podocyte injury was examined in a rat model of diabetic nephropathy
      (DN). Type II diabetic rats with DN were treated with triptolide at a dose of 100
      MUg.kg-1.day-1. Following 8 weeks of triptolide treatment, the urine albumin
      level, kidney weight/body weight and the number of cells positive for ED-1 (a
      marker for rat mononuclear macrophages) in the kidney were assessed. The effects
      of triptolide on podocyte injury and chronic inflammation were analyzed using
      quantitative polymerase chain reaction (qPCR), western blotting and
      immunohistochemistry. Following triptolide treatment, the albuminuria in the type
      II diabetic rats was significantly reduced. Furthermore, the glomerular
      hypertrophy and foot process effacement were improved, and there was a recovery
      of the slit diaphragm associated with nephrin and podocin expression. The
      inflammation in the kidneys was also attenuated. Furthermore, triptolide
      significantly reduced the expression of transforming growth factor-beta1 and
      osteopontin, and the infiltration of ED-1-positive cells into the kidney. The
      results demonstrated that triptolide markedly attenuated albuminuria and podocyte
      injury in the rat model of DN, which may have been correlated with the inhibition
      of inflammation and macrophage infiltration in the kidneys.

PMID- 24137242
TI  - The prediction of T- and B-combined epitope and tertiary structure of the Eg95
      antigen of Echinococcus granulosus.
AB  - Echinococcosis, also known as hydatid disease, is a type of zoonotic parasitic
      disease caused by the Echinococcus larvae infection. The disease is severely
      harmful to both humans and animals. Research and development of an epitope
      vaccine is crucial. To determine the dominant epitopes of the Eg95 antigen, the
      tertiary structure and the T- and B-combined epitope of the Eg95 protein for
      Echinococcus granulosus were predicted and analyzed in the present study. The
      tertiary structure of the Eg95 protein was predicted using the 3DLigandsite
      server and RasMol software. The T- and B-combined epitope of the Eg95 antigen was
      analyzed using the DNAStar (V5.0), IEDB, SYFPEITHI and BIMAS. Tertiary structure
      prediction results showed that there were potential epitopes in Eg95 antigen.
      Bioinformatics analysis revealed the T- and B-combined epitopes of Eg95 antigen.
      Four and six T- and B-combined epitopes induced immune responses in humans and
      mice. Additionally, four T- and B-combined epitopes induced immune responses in
      both humans and mice. The tertiary structure and T- and B-combined epitopes of
      the Eg95 protein were also determined. The results obtained in the present study
      may be beneficial in the investigation of Eg95 antigenicity and the development
      of dominant epitope vaccines.

PMID- 24137243
TI  - Berberine protects against esophageal mucosal damage in reflux esophagitis by
      suppressing proinflammatory cytokines.
AB  - This study was performed to investigate the effects of berberine (BB) in a rat
      model of gastroesophageal reflux disease (GERD), induced by pylorus and
      forestomach ligation. We evaluated cytotoxicity and proinflammatory biomarkers
      (nitric oxide, interleukin (IL)-1beta and prostaglandin E2) in RAW 264.7 cells in
      vitro and anti-inflammatory effects in vivo. A total of 54 Sprague Dawley rats
      were divided into six groups: intact control rats; reflux esophagitis (RE)
      control rats; RE rats treated with 20 mg/kg omeprazole and RE rats treated with
      BB at doses of 20, 40 and 60 mg/kg, respectively. All rats were fasted. RE was
      induced by pylorus and forestomach ligation one hour subsequent to the oral
      treatment. Six hours subsequent to the surgery, the rats were sacrificed, blood
      was collected from the abdominal vein and the esophagus and stomach were
      dissected. The gastric volume and the pH of the gastric juice were evaluated,
      prior to the esophagus being cut longitudinally and an inner mucosal area being
      imaged, to analyze mucosal damage indices. Proinflammatory biomarkers in the
      serum, including tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6 and monocyte
      chemoattractant protein (MCP)-1 were analyzed using an enzyme-linked
      immunosorbent assay (ELISA) kit, while the mRNA expression of TNF-alpha, IL
      1beta, IL-6 and plasminogen activator inhibitor (PAI)-1 was analyzed using a
      quantitative polymerase chain reaction (qPCR). Esophagic tissue damage in the BB
      groups was dose-dependently decreased compared with that in the RE control group.
      This result was consistent with significant reductions in the levels of
      proinflammatory biomarkers in the serum and in the expression of proinflammatory
      mRNA, specifically, TNF-alpha, IL-1beta, IL-6 and PAI-1. The results suggest that
      the anti-inflammatory and protective effects of BB may attenuate the severity of
      RE and prevent esophageal mucosal damage, in addition to validating the use of BB
      as a pharmacological treatment for esophageal reflux disease.

PMID- 24137244
TI  - Bone marrow stromal cells inhibit caspase-12 expression in rats with spinal cord
      injury.
AB  - The mechanisms underlying the potentially beneficial effect of bone marrow stem
      cells (BMSCs) on spinal cord injury (SCI) are unknown. Therefore, the aim of the
      present study was to explore the protective effect of BMSCs in rats with SCI. A
      total of 45 adult male Sprague-Dawley rats were randomly divided into three
      groups; the SCI group (n=15), the BMSC group (n=15) and the sham-operation group
      (n=15). In the SCI and BMSC treatment groups, a modified Allen's weight-drop
      technique was used to induce SCI. The BMSC treatment group received an injection
      of BMSCs using a microneedle into the epicenter of the spinal cord 24 h after
      injury. Rats in the sham-operation group were not subjected to SCI; however, the
      corresponding vertebral laminae were removed. Seven days after transplantation, a
      rapid recovery was observed in the Basso, Beattie and Bresnahan (BBB) scores of
      the BMSC treatment group, whereas the BBB scores in the SCI group remained low
      (P<0.05). Caspase-12 expression in the SCI group was increased compared with that
      in the sham-operation group, whereas caspase-12 expression was attenuated 24 h
      after transplantation in the BMSC treatment group (P<0.05). In conclusion, the
      transplantation of BMSCs may improve locomotor function and attenuate caspase-12
      expression following SCI. Therefore, it is likely to be an effective strategy for
      preventing severe injury of the spinal cord.

PMID- 24137245
TI  - Case report of small bowel obstruction caused by small intestinal metastasis of
      bilateral breast cancer.
AB  - A 41-year-old female was admitted into hospital due to recurrent abdominal pain
      with bloating. An enteroscopy was carried out and stenosis in the lower jejunal
      lumen was identified. This led to a diagnosis of small bowel obstruction caused
      by inflammation. During the laparotomy, the resection and anastomosis of a narrow
      segment of small intestine was performed. In combination with the results of
      immunohistochemical analysis, the postoperative pathology indicated the presence
      of a poorly differentiated/undifferentiated carcinoma of the small intestine,
      which was considered to have arisen from breast cancer. Postoperative examination
      showed bilateral breast masses, and the pathology of the right breast tumor
      biopsy prompted the diagnosis of invasive lobular carcinoma. A breast MRI was
      reviewed following five cycles of XT chemotherapy and the evaluation was stable
      disease (SD). Since the mass was not sensitive to chemotherapy, a bilateral
      modified radical mastectomy was performed, and postoperative pathology confirmed
      the mass to be primary bilateral invasive lobular carcinoma.

PMID- 24137246
TI  - Expression of the nociceptin/orphanin FQ receptor in the intestinal mucosa of IBS
      patients.
AB  - Nociceptin/orphanin FQ (N/OFQ) and the N/OFQ peptide (NOP) receptor play
      important roles in regulating gastrointestinal function. To assess whether the
      NOP receptor is implicated in the etiopathogenesis of irritable bowel syndrome
      (IBS), we measured the levels of NOP receptor mRNA and protein in the jejunal and
      colonic tissues of healthy subjects and patients with diarrhea-predominant IBS (D
      IBS) and constipation-predominant IBS (C-IBS). Mucosal biopsies were obtained
      from the jejunum and colon of patients diagnosed with D-IBS and C-IBS by the Rome
      III criteria and from healthy control subjects. The expression of NOP receptor
      mRNA was measured quantitatively using quantitative PCR (qPCR) and NOP protein
      expression was assayed immunohistochemically using a rabbit monoclonal antibody
      to OFQ. NOP receptor mRNA was detected in the jejunum and colon of healthy
      subjects and was more highly expressed in the jejunum than in the colon.
      Expression was lower in the jejunum and colon of patients with D-IBS; however, it
      was similar in patients with C-IBS and healthy subjects. The numbers of OFQ
      positive cells in the jejunum and colon were similar among the three groups. The
      NOP receptor may be involved in the regulation of intestinal movement in healthy
      individuals. Its involvement in the pathophysiology of IBS may depend on whether
      the IBS is constipation- or diarrhea-predominant.

PMID- 24137247
TI  - Effects of an aqueous extract of Eucommia on articular cartilage in a rat model
      of osteoarthritis of the knee.
AB  - Osteoarthritis is a common chronic and progressively degenerative joint
      condition. The stem bark of Eucommia ulmoides Oliver (a member of the
      Eucommiaceae family), which is also known as Du-Zhong, is a traditional Chinese
      medicine commonly used for the treatment of rheumatoid arthritis. However, the
      mechanisms underlying the effects of Eucommia in the treatment of arthritis of
      the knee require further study. The present study investigated the effects of an
      aqueous extract of Eucommia on the articular cartilage (by Mankin's grade) and
      the levels of matrix metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 in the serum
      and synovial fluid in a rat model of osteoarthritis. The serum levels of MMP-1, 
      3 and -13 were measured by double-antibody sandwich enzyme-linked immunosorbent
      assay (ELISA) at weeks 1, 2 and 4. The levels of MMP-1, -3 and 13 were
      significantly decreased in the rats treated with Eucommia compared with those in
      the control rats (P<0.05). Histopathological examination results indicated a
      lower Mankin's grade in the Eucommia group compared with that of the control
      rats. Therefore, Eucommia was demonstrated to have a cartilage-protecting effect
      in rats with osteoarthritis, potentially by improving cartilage metabolism,
      regulating the degradation of the extracellular matrix of the articular
      cartilage, and inhibiting apoptosis in chondrocytes, thereby slowing down joint
      degeneration.

PMID- 24137248
TI  - Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic
      fatty rats.
AB  - The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which
      are natural antioxidants. The aim of this study was to determine the ANC
      composition of Thai Morus alba L. fruits and to assess the effect of an ANC
      extract on blood glucose and insulin levels in male leptin receptor-deficient
      Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were
      identified by high-performance liquid chromatography-electrospray ionization-mass
      spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body
      weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC
      dose had an effect on body weight. Following 5 weeks of treatment, glucose levels
      were observed to increase from 105.5+/-8.7 to 396.25+/-21 mg/dl (P<0.0001) in the
      CMC-treated ZDF rats; however, the glucose levels were significantly lower in the
      rats treated with 125 or 250 mg/kg ANCs (228.25+/-45 and 131.75+/-10 mg/dl,
      respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs
      normalized glucose levels in the ZDF rats towards those of the lean littermates.
      Insulin levels were decreased significantly in the ZDF rats treated with CMC or
      125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs.
      Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration
      compared with the islets in CMC-treated rats. This study, demonstrated that ANCs
      extracted from Morus alba L. were well tolerated and exhibited effective anti
      diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic
      compounds that may be useful in the prevention of type 2 diabetes.

PMID- 24137249
TI  - Parasuicidal poisoning by intramuscular injection of insecticide: A case report.
AB  - Suicidal poisoning by ingestion of organophosphate (OP) insecticides represents a
      serious emergency with a high mortality rate. However, attempted suicide via the
      parenteral route has rarely been reported. The present study reports a case of
      parasuicide by self-injection of an organophosphorus insecticide (phoxim,
      phenylglyoxylonitrile oxime O,O-diethyl phosphorothioate) into the distal region
      of the left arm. The patient developed necrosis at the injection site and an
      abscess of the affected limb following injection. A fasciotomy and surgical
      debridement resulted in the symptoms of the patient disappearing within a few
      days and were vital in shortening the course of the disease.

PMID- 24137250
TI  - The effect of electroacupuncture on postoperative immunoinflammatory response in
      patients undergoing supratentorial craniotomy.
AB  - The aim of this study was to explore the effect of electroacupuncture (EA) on
      immune function in patients undergoing supratentorial craniotomy. We also
      examined whether point specificity in EA was present. The study involved 29
      patients undergoing craniotomy. The patients were divided into three groups: a
      control (C, n=10), an EA (A, n=9) and a sham acupoints group (S, n=10). Blood
      samples were collected at the following time points: before anesthesia (T0), 4 h
      after the induction of anesthesia (T1), 1 day post-surgery (T2) and 2 days post
      surgery (T3) to determine the levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-8 (IL-8), interleukin-10 (IL-10), immunoglobulin M (IgM), IgA and
      IgG. Data were analyzed using SPSS 13.0 software. When comparing the levels of
      cytokines following surgery, we observed that the peripheral blood IL-8 levels in
      groups A and S were increased significantly compared with those of group C at 1
      and 2 days after surgery. When comparing immunoglobulin levels after surgery, we
      established that the peripheral blood IgA levels in group C had decreased
      significantly compared to those of group A and group S 4 h after induction of
      anesthesia and 1 day after surgery. However, there was no significant difference
      between group A and group S. Compared with simple general anesthesia, acupuncture
      combined with anesthesia partially reduces immune suppression in the
      perioperative periods under the same conditions as the simple general anesthesia.
      Point specificity in EA was not present.

PMID- 24137251
TI  - Effects of exposure to nanoparticle-rich diesel exhaust on 8-OHdG synthesis in
      the mouse asthmatic lung.
AB  - It has been demonstrated that exposure to diesel exhaust (DE) is associated with
      the induction and exacerbation of respiratory disorders; however, the impacts of
      DE containing mainly nanoparticles have been less studied. We have previously
      demonstrated that inhalation exposure to nanoparticle-rich DE (NR-DE) exacerbated
      allergic pulmonary inflammation, in the context of enhanced local expression of
      proinflammatory molecules. However, the underlying mechanisms have not been fully
      elucidated. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative damage,
      particularly in DNA. This study examined the effects of NR-DE on 8-OHdG synthesis
      in the lung in the presence or absence of an allergen. Institute for Cancer
      Research (ICR) mice were exposed by inhalation to four different gas compositions
      (control air, low-concentration DE, high-concentration DE and high-concentration
      DE without particulate matter) for 8 weeks, in the presence or absence of
      repetitive intratracheal administration of ovalbumin (OVA). Thereafter, we
      assessed the levels of 8-OHdG synthesis and expression in the lungs by means of
      enzyme immunoassay (EIA) and immunohistochemistry. The EIA revealed that the
      level of 8-OHdG was significantly higher in the high-concentration NR-DE-exposed
      and allergen-sensitized/stimulated group compared with that in the control air
      exposed and allergen-treated group. The immunohistochemistry results demonstrated
      that the level of immunoreactive 8-OHdG was higher in the NR-DE-exposed and
      allergen-treated lungs compared with that in the corresponding control air
      exposed lungs. The results suggested that NR-DE exposure enhanced 8-OHdG
      formation in asthmatic lungs. This, at least in part, is involved in the NR-DE
      mediated exacerbation of the allergic pathophysiology that was identified in our
      previous study.

PMID- 24137252
TI  - Integrin-mediated osteoblastic adhesion on a porous manganese-incorporated TiO2
      coating prepared by plasma electrolytic oxidation.
AB  - This study was conducted to evaluate the bioactivity of manganese-incorporated
      TiO2 (Mn-TiO2) coating prepared on titanium (Ti) plate by plasma electrolytic
      oxidation (PEO) technique in Ca-, P- and Mn-containing electrolytes. The surface
      topography, phase and element compositions of the coatings were investigated
      using scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy
      dispersive spectrometry (EDS), respectively. The adhesion of osteoblast-like MG63
      cells onto Ti, TiO2 and Mn-TiO2 surfaces was evaluated, and the signal
      transduction pathway involved was confirmed by the sequential expression of the
      genes for integrins beta1, beta3, alpha1 and alpha3, focal adhesion kinase (FAK),
      and the extracellular regulated kinases (ERKs), including ERK1 and ERK2. The
      results obtained indicated that Mn was successfully incorporated into the porous
      nanostructured TiO2 coating, and did not alter the surface topography or the
      phase composition of the coating. The adhesion of the MG63 cells onto the Mn
      incorporated TiO2 coating was significantly enhanced compared with that on the Mn
      free TiO2 coating and the pure Ti plates. In addition, the enhanced cell adhesion
      on the Mn-TiO2 coatings may have been mediated by the binding of the integrin
      subunits, beta1 and alpha1, and the subsequent signal transduction pathway,
      involving FAK and ERK2. The study indicated that the novel Mn-TiO2 coating has
      potential for orthopedic implant applications, and that further investigations
      are required.

PMID- 24137253
TI  - Correlation between gastrointestinal hormones and anxiety-depressive states in
      irritable bowel syndrome.
AB  - The aim of this study was to investigate the mechanism(s) of action of
      gastrointestinal hormones in the pathogenesis of irritable bowel syndrome (IBS),
      and the correlation between gastrointestinal hormones and psychological factors.
      Patients with IBS were divided into IBS with normal emotional state ratings and
      IBS in anxiety-depressive states groups. The two groups were then subdivided into
      IBS-constipation predominant (IBS-C) and IBS-diarrhea predominant (IBS-D) groups.
      Non-IBS patients with normal depression and anxiety ratings were recruited as
      controls. The serum concentrations of somatostatin (SS) and vasoactive intestinal
      peptide (VIP) were measured by radioimmunoassay, and the expression of SS and VIP
      in the colonic mucosa was detected by immunohistochemistry and radioimmunoassay.
      The anxiety-depression scores of patients with IBS were significantly different
      from those of the control group (P<0.05). The expression levels of SS and VIP in
      the serum and colonic mucosa of the patients with IBS were higher compared with
      those of the control group. Furthermore, the expression level of SS in the IBS-C
      group demonstrated a significantly larger increase than that in the IBS-D group
      (P<0.05); however, there was no significant difference in the expression of VIP
      between the IBS-C and IBS-D groups (P>0.05). In addition, the expression levels
      of SS and VIP in the IBS groups with normal emotional state ratings were notably
      different from those in the IBS groups in anxiety-depressive states (P<0.05).
      Anxiety-depressive states may lead to changes in the secretion of SS and VIP, and
      subsequently to changes in gastrointestinal motility and function.

PMID- 24137254
TI  - Effects of long-term atorvastatin treatment on cardiac aging.
AB  - A number of studies have reported that atorvastatin (AVT) may have an important
      role in the delay of cardiac aging. However, the mechanism by which AVT affects
      cardiac aging has not been established. In this study, a series of experiments
      were performed to investigate the effects of AVT treatment on the cardiovascular
      system and the associated mechanism. Wistar rats were administered AVT or saline
      for 4 months. Age-related changes in the hearts were measured at the end of the
      experiment. The results showed that compared with young rats, the aged rats had
      significant changes indicative of myocardial aging, including increased blood
      lipid 1evelss, increased body weight, cardiac hypertrophy, larger myocardial
      cells, irregular muscle fibers, fewer deeply stained nuclei, smaller
      intercellular spaces, a larger number of apoptotic cells and increased levels of
      lipofuscin in myocardial tissue. However, long-term AVT treatment was able to
      significantly delay or even reverse these aging-related changes. In addition,
      these effects showed a certain dose-dependence. In general, long-term AVT
      treatment reduces blood lipids, inhibits cardiac hypertrophy, suppresses
      cardiomyocyte apoptosis and lowers the level of oxidative stress to protect the
      heart from aging.

PMID- 24137255
TI  - Application of adenosine stress echocardiography in the prognosis of acute
      myocardial infarction following percutaneous coronary interventional therapy.
AB  - The aim of this study was to investigate the application of adenosine stress
      echocardiography (ASE) in the prognosis of acute myocardial infarction (AMI)
      following percutaneous coronary intervention (PCI). A total of 79 patients with
      AMI who underwent PCI were selected for the study. ASE testing was performed
      within one week following the PCI. Subsequent to the ASE, the patients with >=5%
      increases in the left ventricular ejection fraction (LVEF) levels were included
      in the improved LVEF group, while patients with <5% increases in LVEF levels were
      included in the unimproved LVEF group. A follow-up study was performed during the
      24 months subsequent to the ASE. The incidence of major adverse cardiovascular
      events (MACEs) was observed and compared between the two groups and logistic
      regression analysis was applied to identify the risk factors for clinical
      prognosis. There were no significant differences in Killip classification, LVEF,
      left ventricular end-diastolic diameter or blood plasma B-type natriuretic
      peptide concentration between the two groups following PCI. The incidence of
      MACEs in the improved LVEF group was significantly lower than that in unimproved
      LVEF group (14.29 versus 43.24%, respectively; P<0.05). Logistic regression
      analysis identified LVEF increases of <5% and segment improvements of <=3 as the
      risk factors for the clinical prognosis of AMI following treatment with PCI.
      Therefore, ASE is an effective method of assessing the clinical effect of PCI
      treatment, which may be utilized to predict the incidence of MACEs following PCI.

PMID- 24137256
TI  - Asiatic acid ameliorates tubulointerstitial fibrosis in mice with ureteral
      obstruction.
AB  - Asiatic acid (AA) is one of the triterpenoid compounds present in Centella
      asiatica and it has been shown to be capable of attenuating liver fibrosis. In
      the present study, we investigated the effects of AA on renal tubulointerstitial
      fibrosis in mice with unilateral ureteral obstruction (UUO). Mice were divided
      randomly into five groups (n=5 per group): the sham-surgery (Sh), UUO plus
      vehicle treatment (UUO+V), UUO plus 1 mg/kg body weight AA treatment (UUO+A1),
      UUO plus 4 mg/kg body weight AA treatment (UUO+A2) and UUO plus 16 mg/kg body
      weight AA treatment (UUO+A3) groups. The mice were treated with AA daily by oral
      gavage from the day subsequent to surgery for six days. On the seventh day, the
      mice were sacrificed for examination. Tubular injury was observed in the renal
      cortex of the mice administered the vehicle, while high doses of AA were observed
      to exert a significant suppressive effect on tubular injury. Interstitial
      fibrosis, increased expression of alpha-smooth muscle actin (SMA) and
      transforming growth factor (TGF)-beta1 and phosphorylation of Smad2/3 were
      induced by ureteral ligation; however these effects were abrogated by
      intermediate and high doses of AA. These results suggest that AA may ameliorate
      tubulointerstitial fibrosis by reducing tubular injury, fibroblast activation and
      extracellular matrix (ECM) accumulation mediated by Smad-dependent TGF-beta1
      signaling.

PMID- 24137257
TI  - Application of clinical PET imaging to human laryngeal squamous cell carcinoma
      xenografts.
AB  - Positron emission tomography (PET) imaging with [F-18]-fluoro-2-deoxy-D-glucose
      (18F-FDG) is extensively applied in clinical practice. However, in animal
      experiments, the application of clinical PET is difficult, due to limitations in
      sensitivity and spatial resolution. This study aimed to determine the potential
      of 18F-FDG PET with regard to the imaging of human laryngeal squamous cell
      carcinoma (LSCC) xenografts. Twenty-seven LSCC tumor-bearing nude mice were
      divided randomly into seven groups which were each handled differently; the
      anesthetization, fasting, warming and the time point at which scanning was
      initiated were varied. The size of each xenograft was measured prior to
      conducting the scan. Using the RAMLA 3D image reconstruction method, images were
      acquired. The region of interest (ROI) technology was adopted to calculate target
      and non-target (T/N) ratios. The results were subsequently analyzed by
      semiquantitative analysis. The analysis showed that there was no significant
      correlation between tumor size and PET image quality (r=0.381, P>0.05); however,
      the handling conditions of the mice had a greater influence on the tumor image
      quality. Fasting increased 18F-FDG uptake (T/N, 1.153+/-0.008) to a certain
      degree, although the effect was unstable. By contrast, combining warming and
      fasting increased 18F-FDG uptake significantly (T/N, 2.0+/-0.29; P<0.05). The
      acquisition time had no impact on the tumor image quality. The study demonstrated
      that the application of clinical PET scanning has potential in the study of human
      LSCC xenografts in nude mice, and that the quality of the image of the tumor is
      greatly influenced by the handling conditions of the animals.

PMID- 24137258
TI  - Andrographolide inhibits the activation of NF-kappaB and MMP-9 activity in H3255
      lung cancer cells.
AB  - This study aimed to determine the effect of andrographolide (AD) on the growth of
      H3255 lung cancer cells and its possible impact on the expression and activity of
      the matrix metalloproteinase (MMP)-9 protein. H3255 cells were cultured in vitro,
      and treated with AD (1, 5 or 10 MUM) for 24, 48 or 72 h. Cell proliferation was
      detected using an MTT assay and the expression of MMP-9 mRNA was measured using a
      reverse transcription-polymerase chain reaction (RT-PCR). The activity of MMP-9
      was assessed by gelatin zymography, while the nuclear translocation of the
      nuclear factor-kappaB (NF-kappaB) p65 subunit and the phosphorylation of IkappaB
      were determined by western blotting. AD inhibited the proliferation of the H3255
      cells in a concentration- and time-dependent manner, in addition to
      downregulating the expression of MMP-9 mRNA and the activity of MMP-9. Moreover,
      AD significantly inhibited the nuclear translocation of the NF-kappaB p65 subunit
      and suppressed IkappaB phosphorylation. The significant inhibition of H3255 cell
      proliferation by AD may have been correlated with the reduction in MMP-9
      expression and activity through the inhibition of the phosphorylation of IkappaB
      and the translocation of NF-kappaB. The results suggest that AD is a promising
      drug candidate for the treatment of the migration and invasion of malignant
      tumors.

PMID- 24137259
TI  - Expression levels of induced sputum IL-8 and IL-10 and drug intervention effects
      in patients with acute exacerbated COPD complicated with chronic cor pulmonale at
      high altitude.
AB  - The aim of this study was to assess the expression levels of induced sputum
      interleukin (IL)-8 and IL-10 levels in patients with acute exacerbated chronic
      obstructive pulmonary disease (AECOPD) complicated with chronic cor pulmonale
      (CCP) at high altitude, and to evaluate the intervention effects of an inhaled
      corticosteroid (ICS) and a beta2-adrenoceptor agonist in this disease. A total of
      186 patients with AECOPD complicated with CCP were randomly divided into three
      groups, with 62 cases in each. With regard to the two treatment groups, group A
      was treated with salmeterol/fluticasone (50 MUg/250 MUg, respectively) by airway
      inhalation twice daily, while group B received budesonide (1 mg) as a spray
      inhalation, twice daily. The routine treatment group (group C) received only
      routine treatment. The levels of IL-8 and IL-10 in the induced sputum and the
      predicted percentage of forced expiratory volume in one second (FEV1%pred),
      partial pressure of oxygen in arterial blood (PaO2) and partial pressure of
      carbon dioxide in arterial blood (PaCO2) were examined on admission and at a
      stable stage two weeks following treatment. Forty healthy volunteers served as a
      control group (group D). Compared with group D values, the IL-8 induced sputum
      level and the PaCO2 were significantly increased, while the level of IL-10,
      FEV1%pred and the PaO2 were markedly decreased in the three COPD groups prior to
      treatment. Following treatment, the induced sputum IL-8 level and the PaCO2 were
      significantly decreased, while the induced sputum IL-10 level, FEV1%pred and the
      PaO2 were markedly increased in the three treatment groups compared with the
      values pre-therapy (all P<0.01). The post-treatment parameters were significantly
      different among the three groups (P<0.01). The results indicate that IL-8 and IL
      10 are involved in the airway inflammation of AECOPD complicated by CCP.
      Treatment with an ICS was demonstrated to be a successful method of reducing the
      local expression of IL-8 and increasing the local expression of IL-10; however,
      ICS combined with a long-acting beta2-adrenoceptor agonist (LABA) was more
      effective than the sole administration of ICS in patients with AECOPD complicated
      by CCP at high altitude.

PMID- 24137260
TI  - Comparison of laparoscopy-assisted surgery and laparotomy for treating locally
      advanced distal gastric antral cancer.
AB  - The aim of this study was to investigate the safety, feasibility and mid-term
      results of laparoscopy-assisted surgery in the treatment of locally advanced
      gastric antral cancer. The clinical data of 50 patients who received laparoscopy
      assisted surgery (Group A) and 62 patients who were treated by conventional
      laparotomy (Group B) from August 2009 to January 2011 were retrospectively
      analyzed. The surgical incision length, the volume of blood loss, the intestinal
      function recovery time, the postoperative complications, the postoperative 1- and
      3-year cumulative survival rates and the average survival time in the two groups
      were observed. The results of the two groups were compared using the chi2 test
      for the enumeration data, a t-test for the numerical data and a Wilcoxon rank sum
      test for the skewed data. In addition, the Kaplan-Meier method of single factor
      analysis was utilized to comwpare the 1- and 3-year cumulative survival rates, as
      well as the average survival time of the two groups. The results indicated that
      the duration of surgery for Group A was significantly longer compared with that
      of Group B (P<0.05); however, the incision length and the volume of
      intraoperative blood loss in Group A were significantly smaller compared with
      those of Group B (P<0.01). Furthermore, in Group A, the recovery of intestinal
      function was more rapid and the time spent in hospital was shorter. However,
      between Groups A and B, the respective number of dissected lymph nodes (16.3 and
      17.2), 1-year survival rates (86.0 and 88.6%) and 3-year survival rates (52.6 and
      53.7%) were not significantly different (P<0.05). The results indicate that
      laparoscopy-assisted surgery is a safe approach for the treatment of locally
      advanced gastric antral cancer and has beneficial treatment effects. Laparoscopy
      assisted surgery is advantageous compared with laparotomy, due to the smaller
      incision length and reductions in intraoperative blood loss, invasiveness,
      postoperative recovery time and the number of complications.

PMID- 24137261
TI  - Mammotome(r) biopsy system for the resection of breast lesions: Clinical
      experience in two high-volume teaching hospitals.
AB  - Ultrasound-guided vacuum-assisted breast biopsy (VABB) is regarded as a feasible,
      effective, minimally invasive and safe method for the removal of benign breast
      lesions, without the occurrence of serious complications. The aim of this study
      was to evaluate the feasibility, efficacy and safety of ultrasound-guided VABB
      using the Mammotome(r) biopsy system in the treatment of breast lesions. The
      clinical outcomes of 3,681 patients with breast lesions were evaluated following
      excisions by ultrasound-guided VABB in two high-volume teaching hospitals. From
      January 2008 to December 2012, a total of 4,867 ultrasound-guided VABB procedures
      were performed in the 3,681 patients, who had a mean age of 37.8 years (range, 16
      73 years). The parameters examined in this analysis included lesion size, lesion
      location in the inner breast, Breast Imaging Reporting and Data System (BI-RADS)
      ultrasound category and histopathological diagnosis. Ultrasonography follow-up
      was performed at 3-6 month intervals in order to assess recurrence. The size of
      the investigated lesions ranged between 6 and 62 mm and a histopathological
      diagnosis was made in 100% of cases. The results indicated that the majority of
      specimens (98.89%) were benign. On average, the ultrasound-guided VABB was
      performed in 10.3 min (range, 7.5-43 min) and the mean number of cores removed in
      the procedure was 8.1 (range, 3-32). A complete excision was achieved in the
      majority of cases (99.7%). The presence of a hematoma was the most common
      complication following the biopsy, and was observed in 27.5% of patients. The
      mean follow-up period was 25.5 months (range, 1-60 months), during which the rate
      of recurrence was 4.4%. The results indicated that ultrasound-guided VABB using
      the Mammotome biopsy system is an effective and safe procedure that is able to
      rapidly remove the majority of benign breast lesions using a small incision and
      without the occurrence of scarring or complications.

PMID- 24137262
TI  - Diagnosis and management of an elderly patient with severe tracheomalacia: A case
      report and review of the literature.
AB  - Severe adult tracheomalacia is a dangerous disease that is difficult to manage,
      particularly at the time of airway infection, and has a high mortality rate. The
      present study reports the diagnosis and treatment of an elderly patient with
      severe adult tracheomalacia. In March 2012, the 59-year-old patient presented
      with progressive dyspnea to the Department of Respiratory Medicine, Taizhou
      People's Hospital (Jiangsu, China). Following admission, chest radiography
      revealed symptoms consistent with chronic obstructive pulmonary disease (COPD)
      and chest computed tomography (CT) demonstrated an evident stenosis of the
      tracheal lumen at the end of expiration. Bronchoscopy revealed a 91% reduction in
      the cross-sectional area of the tracheal lumen at the end of expiration.
      Following the final diagnosis, the patient was successfully treated with nasal
      continuous positive airway pressure (CPAP) combined with implantation of a
      temporary Chinese Li's metallic stent. These treatment methods appeared to be
      temporarily effective in alleviating the symptoms of the disease.

PMID- 24137263
TI  - Ultrasound biomicroscopy of hyperpressurized eyes following pars plana
      vitrectomy.
AB  - Early elevated intraocular pressure (IOP) following pars plana vitrectomy is a
      common complication of vitreoretinal surgery and severe pressure elevation may
      result in visual loss. To investigate the mechanism of IOP elevation following
      pars plana vitrectomy, a retrospective review of 119 patients (132 eyes) who had
      undergone vitreoretinal surgery was performed. Ultrasound biomicroscopy (UBM) was
      used to observe the changes in the structure of the anterior segment following
      vitrectomy and to compare various parameters pre- and postsurgery. The UBM
      examination revealed inflammation within the anterior chamber and hyphema with
      increased IOP. In certain patients, the iris had adhered to the trabecular
      meshwork and the anterior chamber angle was closed. Cyclodialysis involving the
      pars plicata and iris was also observed. Furthermore, silicone oil emulsification
      in the anterior chamber angle and posterior chamber presurgery were noted in
      certain cases. Edema and forward rotation of the ciliary body resulted in the
      closure of the anterior chamber angle. The measured parameters indicated that the
      anterior chamber became shallower and that the anterior chamber angle was
      narrowed in phakic eyes with elevated IOP. Eyes with elevated IOP and intraocular
      lenses were not observed to be different from phakic eyes with elevated IOP. This
      may be due to the fact that an eye with an intraocular lens is thinner than a
      phakic eye. This study suggests that UBM examination is useful for investigating
      the pathogenesis of elevated IOP following vitrectomy, and provides a theoretical
      basis.

PMID- 24137264
TI  - Acupuncture for the treatment of urinary incontinence: A review of randomized
      controlled trials.
AB  - The aim of this study was to examine the effects of acupuncture on urinary
      incontinence and to discuss why these acupoints were selected. Seven databases
      were searched for any randomized controlled trials (RCTs) that investigated the
      use of acupuncture or acupressure as a treatment for urinary incontinence, and
      the Cochrane risk of bias tool was utilized to evaluate the risk of bias in each
      study. Four RCTs met all the inclusion criteria. The results from the selected
      RCTs failed to demonstrate any statistically significant improvements in urinary
      incontinence, although acupuncture or acupressure did exhibit favorable effects
      on overactive bladder symptoms and quality of life, in comparison with other
      conventional therapies. There have been limited results supporting acupuncture or
      acupressure as an effective treatment method for urinary incontinence; therefore,
      further RCTs are required to confirm the effectiveness of acupuncture or
      acupressure in the treatment of urinary incontinence.

PMID- 24137265
TI  - Effects of sevoflurane and propofol on the inflammatory response and pulmonary
      function of perioperative patients with one-lung ventilation.
AB  - This study compared the effects of sevoflurane and propofol on the inflammatory
      response and pulmonary function of patients with lung cancer during the
      perioperative period. Forty patients who underwent a selective resection of the
      inferior lobe of the left lung were randomly divided into two groups, with one
      group anesthetized with sevoflurane and the other with propofol (groups S and P,
      respectively). Radial arterial and mixed venous blood were extracted for blood
      gas analysis, in order to calculate the alveolar-arterial oxygen partial pressure
      difference (PA-aDO2), respiratory index (RI) and pulmonary shunt ratio (Qs/Qt)
      prior to the induction of anesthesia (T0), prior to one-lung ventilation (OLV)
      (T1), 1 h subsequent to the commencement of OLV (T2), 1 h following restoration
      of two-lung ventilation (T3), 2 h following restoration of two-lung ventilation
      (T4) and 24 h post-surgery (T5). In addition, blood was extracted from the radial
      artery at T0, T1, T2, T3, T4 and T5 in order to detect the presence of tumor
      necrosis factor-alpha (TNF-alpha), IL-6 and IL-10 in the blood serum. Between T1
      and T4, the tidal volume, airway plateau pressure and end-expiratory positive
      airway pressure were recorded, in order to calculate the lung dynamic compliance
      (Cdyn). Heart rate, mean arterial pressure, central venous pressure, cardiac
      output and the duration of OLV (OLV-T) were recorded at T0-5. Compared with T0,
      the levels of TNF-alpha, IL-6 and IL-10 significantly increased during T2 to T4
      in both groups (P<0.05). PA-aDO2 and RI increased during T1 to T4, and Qs/Qt
      increased at T2 (P<0.05). Compared with T1, Cdyn decreased during T2 to T4 in the
      S group, whereas Cdyn was reduced at T2 in the P group (P<0.05). Compared with
      the P group, TNF-alpha level increased and IL-10 decreased at T3 and T4 in the S
      group. PA-aDO2 and RI increased, but Cdyn decreased at T2 and T3 in the S group.
      Qs/Qt increased at T2 in the S group. The results of the present study
      demonstrated that, in comparison with propofol, sevoflurane exhibited an enhanced
      capacity to aggravate injury to pulmonary function during the perioperative
      stages. This occurred via the release of inflammatory factors, the aggravation of
      lung edema and the inhibition of hypoxic pulmonary vasoconstriction.

PMID- 24137266
TI  - Conjugates of cytochrome c and antennapedia peptide activate apoptosis and
      inhibit proliferation of HeLa cancer cells.
AB  - Polycationic cell-penetrating peptides (CPPs) deliver macromolecules into cells
      without losing the functional properties of the cargoed macromolecule. The aim of
      this study was to determine whether exogenous cytochrome c is delivered to HeLa
      cervical carcinoma cells by the CPP antennapedia (Antp) and activates apoptosis.
      HeLa cervical carcinoma cells were treated with conjugated Antp-SMCC-cytochrome c
      (cytochrome c chemically conjugated to Antp) or with non-conjugated Antp and
      cytochrome c. Sensitivity to the treatments was determined by the clonogenic
      assay (proliferation) and by immunoblot analysis (apoptosis activation). We
      report that conjugated Antp-SMCC-cytochrome c activated apoptosis in HeLa cells
      as demonstrated by poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and inhibited
      their proliferation. The Antp-SMCC-cytochrome c-induced apoptosis was inhibited
      by z-VAD-fmk, a pan-caspase inhibitor peptide. Unconjugated Antp or cytochrome c
      demonstrated no inhibitory effect on survival and proliferation. Our results
      suggest that chemical coupling of cytochrome c to CPPs may present a possible
      strategy for delivering cytochrome c into cells and for activating apoptosis.

PMID- 24137267
TI  - Hypophosphatemic vitamin D-resistant osteomalacia: A case report.
AB  - This study concerns the case of a 59-year-old woman who was admitted to hospital
      after experiencing systemic bone pain and muscle weakness for more than 2 years.
      The patient was diagnosed with numerous fractures via bone imaging emission
      computed tomography (ECT) and hypophosphatemia. Laboratory results showed a high
      alkaline phosphatase concentration. Thyroid nodules were visible on the thyroid
      and parathyroid glands during ultrasound examinations. However, no symptomatic or
      biochemical improvement was observed following a thyroid nodulectomy. The patient
      was administered large doses of neutral phosphate preparations, vitamin D3 and
      calcium. A gradual improvement in the condition of the patient was observed. For
      bone pain associated with multiple fractures in elderly patients, calcium and
      phosphorus metabolism disorders, and active vitamin D deficiency should be
      considered and an early diagnosis should be performed.

PMID- 24137268
TI  - Synthesis and hepatoprotective properties of Acanthus ilicifolius alkaloid A and
      its derivatives.
AB  - Acanthus ilicifolius alkaloid A (4-hydroxy-2(3H)benzoxazolone, HBOA) is a
      naturally occurring compound that has been separated from Acanthus ilicifolius.
      Previous studies have reported the beneficial effects of HBOA on HSC-T6 cells.
      This study was undertaken in order to synthesize HBOA and two of its derivatives,
      specifically, 4-acetoxy-2(3H)-benzoxazolone (AcO-BOA) and 3-acetyl-4-acetoxy-2
      benzoxazolone (TC-3), and to investigate the hepatoprotective potentials of these
      three compounds on CCl4-induced liver injury in mice. HBOA was prepared from 2
      nitroresorcinol by a 'one pot' reduction and subsequent cyclization with urea.
      The acyl derivatives, AcO-BOA and TC-3, were prepared from HBOA using a
      substitution reaction. The compounds were synthesized with good yields (63.08
      68.22%). An acute liver injury model was established by administering CCl4
      intraperitoneally to Kunming mice. The mice were then intragastrically
      administered bifendate (150 mg/kg) or the synthesized compounds at three
      different doses (200, 100 and 50 mg/kg). The treatment with CCl4 was observed to
      increase the levels of aminotransferase (ALT), aspartate aminotransferase (AST),
      lactic dehydrogenase (LDH) and malondialdehyde (MDA) and decrease the levels of
      superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione
      peroxidase (Gpx) in the liver tissues of the mice. Furthermore, treatment with
      CCl4 elevated the expression level of the proinflammatory mediator TNF-alpha.
      However, HBOA and its derivatives attenuated the changes induced by CCl4.
      Furthermore, CCl4-induced histopathological changes were reduced by treatment
      with these compounds. These results suggest that HBOA and its acyl derivatives
      are able to significantly alleviate the hepatotoxicity induced by CCl4 in mice.

PMID- 24137269
TI  - Analysis of the efficacy of lenalidomide in patients with intermediate-1 risk
      myelodysplastic syndrome without 5q deletion.
AB  - The aim of this study was to evaluate the efficacy and adverse effects of
      lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del
      (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were
      classified through G-banding chromosome karyotype analysis and fluorescence in
      situ hybridization (FISH). According to the International Prognostic Scoring
      System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and
      1.0, respectively. Lenalidomide (Revlimid(r)), 10 mg/day) was administered for 21
      days every 28 days. All 30 cases were treated with lenalidomide for at least
      three cycles, including 20 cases with four cycles. The patients did not require
      erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis
      was performed using SPSS statistical software version 13.0, and comparisons among
      groups were conducted using a t-test. The efficacy of lenalidomide was
      demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral
      blood cell counts were improved following treatment, and absolute neutrophil,
      haemoglobin and platelet counts increased following 2-4 cycles of treatment. All
      patients became stable having undergone three cycles of treatment; however, 17
      patients with chromosomal abnormalities had no cytogenetic response to the
      treatment, as confirmed through the FISH test. Patients with intermediate-1 risk
      non-del (5q) MDS treated with lenalidomide did not achieve complete
      haematological remission, although they demonstrated haematological improvement.

PMID- 24137270
TI  - Successful treatment of non-small cell lung tumor with 15 lesions by CyberKnife
      radiosurgery: A case report.
AB  - Stereotactic body radiation therapy (SBRT) plays an important role in the
      treatment of early stage non-small cell lung cancer (NSCLC), particularly when
      patients are unable to tolerate surgical resection due to comorbid conditions or
      are unwilling to undergo surgery. High rates of local tumor control that may
      rival the results of surgery have been demonstrated in certain cases with the
      practical advantage of a short course of treatment and acceptable toxicity.
      However, there are few reports of a marked change in the complete response of
      high risk lung cancer with more than ten lesions. In the present study, we report
      a case of adenocarcinoma of the lung with 15 lesions which had metastasized to
      the mediastinal lymph nodes. Due to advanced age, multiple lesions and metastasis
      to the mediastinal lymph nodes and the hilar region of the lung, the patient was
      treated using CyberKnife. A marked response was noted 42 days after CyberKnife
      radiosurgery with complete disappearance of the tumor and metastastic lesions.

PMID- 24137271
TI  - Safety and efficacy of a non-polymeric paclitaxel-eluting microporous stent in
      real-world percutaneous coronary intervention.
AB  - At present, there is an increasing focus on stents that have a biodegradable
      polymer coating, rather than a permanent polymer coating. This is due to the fact
      that following the implantation of a drug-eluting stent (DES) with a permanent
      polymer coating, the continued existence of the coating may result in a foreign
      body reaction and delayed re-endothelialization. The aim of the present study was
      to evaluate the safety and efficacy of a non-polymeric paclitaxel-eluting
      microporous (YINYITM) stent in real-life percutaneous coronary intervention (PCI)
      for patients with coronary artery disease (CAD). A total of 686 YINYITM stents
      were implanted in 404 patients with CAD in a PCI procedure and outpatient follow
      ups were performed 1, 6, 12 and 15 months subsequent to the PCI, respectively.
      The observation endpoints were major adverse cardiac events (MACEs), including
      cardiac death, non-fatal myocardial infarction (MI), restenosis, target lesion
      revascularization, stent thrombosis and recurrence of angina pectoris. The
      average follow-up time was 15 months. The results revealed that the cumulative
      incidences of MACEs were as follows: mortality, 0.99%; non-fatal MI, 0.74%;
      restenosis, 4.0%; and target lesion revascularization, 2.7%. The results at the
      short- and long-term clinical follow-ups indicated that YINYITM stents are
      effective and safe for use in PCI for patients with CAD.

PMID- 24137272
TI  - Splenogonadal fusion: Report of four cases and review of the literature.
AB  - Splenogonadal fusion (SGF) is a rare congenital abnormality that affects children
      of both genders. Very few cases of SGF have been diagnosed preoperatively. In
      this study, the surgical findings and laparoscopic treatment of four children
      with SGF associated with intra-abdominal cryptorchidism are described.
      Laparoscopy was demonstrated to be the only accurate exploratory procedure for
      the diagnosis and surgical treatment of SGF with non-palpable testis.

PMID- 24137274
TI  - Panax notoginsenoside Rb1 ameliorates Alzheimer's disease by upregulating brain
      derived neurotrophic factor and downregulating Tau protein expression.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder and the main cause of
      dementia. Panax notoginsenoside Rb1 (PNRb1), which is also known as
      (3beta,12beta)-20-[(6-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]-12
      hydroxydammar-24-en-3-yl 2-O-beta-D-glucopyranosyl-beta-D-glucopyranoside and is
      the main active component of the plant Panax notoginseng, is effective in
      treating AD. However, the mechanisms of PNRb1 remain unknown. In the present
      study, rat brain tissue sections were pretreated with PNRb1 and then induced by
      okadaic acid to establish brain slice models of AD. The results of qPCR and
      immunoblot analyses demonstrated that PNRb1 suppressed the protein expression of
      phosphorylated Tau and upregulated the expression levels of brain-derived
      neurotrophic factor (BDNF). These results suggest that PNRb1 is able to
      upregulate the protein level of BDNF and downregulate Tau protein phosphorylation
      in AD.

PMID- 24137273
TI  - Comparison of cilostazol versus ticlopidine following coronary stenting in
      patients with coronary heart disease: A meta-analysis of randomized controlled
      trials.
AB  - Previous studies have shown that the combination of cilostazol and aspirin may be
      a more effective regimen than ticlopidine plus aspirin in the prevention of late
      restenosis and acute or subacute stent thrombosis following coronary stenting;
      however, individually published results are inconclusive. The aim of this meta
      analysis was to compare the differences in late restenosis and stent thrombosis
      between cilostazol plus aspirin and ticlopidine plus aspirin for patients with
      coronary heart disease (CHD) following coronary stenting. A literature search of
      Pubmed, Embase, Web of Science and Chinese BioMedicine (CBM) databases was
      conducted from 1998 to March 1, 2013 and statistical analysis was performed using
      Stata statistical software, version 12.0. Twelve randomized controlled trials
      were included in the study, with a total of 2,708 patients with CHD following
      coronary stenting. The patient population comprised 1,371 patients treated with
      cilostazol plus aspirin and 1,337 patients treated with ticlopidine plus aspirin.
      The meta-analysis showed that cilostazol plus aspirin demonstrated a lower rate
      of restenosis than ticlopidine plus aspirin [odds ratio (OR)=0.83, 95% confidence
      interval (CI)=0.69-0.99, P=0.047]. A significant difference was also observed in
      the average percent diameter stenosis between cilostazol plus aspirin and
      ticlopidine plus aspirin [standardized weight difference (SMD)= -0.57, 95% CI=
      0.92, -0.23, P=0.001). However, there were no significant differences in the
      rates of acute or subacute stent thrombosis between cilostazol plus aspirin and
      ticlopidine plus aspirin. The present meta-analysis suggests that cilostazol plus
      aspirin may result in a lower restenosis rate and percent diameter stenosis than
      ticlopidine plus aspirin for patients with CHD following coronary stenting.

PMID- 24137275
TI  - Inhibitory role of S-nitrosoglutathione in the aggregation of frozen platelets,
      and its effect on the expression of membrane glycoproteins.
AB  - The aim of this study was to explore the effects of S-nitrosoglutathione (GSNO)
      on the aggregation of frozen platelets, the platelet nitric oxide (NO) content
      and the expression of membrane glycoproteins. The level of frozen platelet
      aggregation was measured using a platelet aggregation analyzer, while the content
      of NO was measured by the nitrate reductase method and the expression of frozen
      platelet membrane glycoproteins was determined by flow cytometry. The level of
      frozen platelet aggregation was reduced from 35.47+/-2.93 to 24.43+/-3.07%
      following treatment with GSNO. The mean NO concentration in the 32 samples of
      frozen platelets treated with GSNO was 45.64+/-6.31 MUmol/l, which was
      significantly higher compared with the concentration in the fresh liquid platelet
      group. There were no significant differences in the levels of PAC-1 in the fresh
      liquid platelet, frozen platelet and GSNO-treated frozen platelet groups; by
      contrast, significant differences were observed in the CD42b and CD62P levels.
      The platelet membrane glycoprotein expression levels in the frozen platelet and
      the GSNO-treated frozen platelet groups were not significantly different. The
      results of the study indicate that GSNO has potential as a cryoprotectant, due to
      its ability to increase the NO concentration in frozen platelets, inhibit
      platelet aggregation and maintain platelet function. It is likely that the
      molecular arrangement and structure of the frozen platelets were altered
      following GSNO treatment, or that the frozen platelets were affected by
      alternative mechanisms.

PMID- 24137276
TI  - Identification of independent risk factors for restenosis following bare-metal
      stent implantation: Role of bare-metal stents in the era of drug-eluting stents.
AB  - In the era of drug-eluting stents (DESs), the ability of clinicians to predict
      which patients have a low risk of coronary restenosis following bare-metal stent
      (BMS) implantion is likely to be of benefit. The study population consisted of
      2,711 patients who underwent BMS implantation in 3,770 lesions between 1995 and
      2004. With clinical and 6 month follow-up angiographic data, we retrospectively
      sought to identify the independent risk predictors of restenosis, applied a
      previously proposed prediction model and assessed the characteristics of patients
      with a low likelihood of coronary restenosis within 6 months of BMS implantation.
      A 6-month follow-up coronary angiography was performed in 65.0% of the patients
      who had undergone the BMS implantation and the rate of restenosis was 26.6%.
      Using multivariate analysis, diabetes [odds ratio (OR), 1.294; 95% confidence
      interval (CI), 1.094-1.483; P=0.005], current smoking (OR, 1.294; 95% CI, 1.094
      1.483; P=0.002), a reference vessel diameter of <3.25 mm (OR, 1.238; 95% CI,
      1.021-1.501; P<0.001), a lesion length of >30 mm (OR, 1.645; 95% CI, 1.336-2.026;
      P<0.001), ostial lesion (OR, 1.858; 95% CI, 1.437-2.402; P<0.001), post-stenting
      minimal luminal diameter (OR, 0.576; 95% CI, 0.484-0.685; P<0.001) and
      bifurcation lesion (OR, 1.353; 95% CI, 1.070-1.711; P=0.012) were identified as
      significant independent predictors of restenosis. However, the accuracy of the
      prediction obtained with the current model, which used the clinical and
      angiographic variables correlated with the risk of restenosis, was poor. Various
      clinical and angiographic independent risk variables were revealed to be
      correlated with the risk of restenosis following BMS implantation in the present
      large dataset. Certain groups of patients with a relatively low risk of
      restenosis may be considered for BMS implantation as an alternative to DESs.
      However, the prediction models used at present are incomplete and further studies
      are required.

PMID- 24137277
TI  - Assessment of IL-6, IL-8 and TNF-alpha levels in the gingival tissue of patients
      with periodontitis.
AB  - In periodontal diseases, inflammatory mediators, including interleukin (IL)-6, IL
      8 and tumor necrosis factor-alpha (TNF-alpha), may promote the degeneration of
      inflamed periodontal tissues. In previous studies, levels of these three
      cytokines were demonstrated to be elevated in inflammatory gingival tissues and
      gingival crevicular fluid. The aim of the present study was to quantify IL-6, IL
      8 and TNF-alpha levels in the human gingival tissues of patients with
      periodontitis and to assess the correlation of these three cytokines with each
      other. In this study, human gingival tissues from 19 patients with periodontitis
      (male, n=14; female, n=5) were collected. The tissues were homogenized,
      centrifuged and the protein in the supernatant was quantified. Enzyme-linked
      immunosorbent assay (ELISA) was used in the measurement of the IL-6, IL-8 and TNF
      alpha levels, and the mean levels were observed to be 8.41+/-0.25, 34.01+/-1.09
      and 20.70+/-0.31 pg/ml, respectively. The mean levels of IL-8 were higher than
      those of the other two cytokines. In each sample, the level of TNF-alpha
      expression was consistently high, with little difference between the results,
      which contrasted with the fluctuations in IL-6 and IL-8 levels. The expression of
      the two ILs (IL-6 and IL-8) showed a positive correlation (r=0.932, P=0.01),
      whereas TNF-alpha levels were not correlated with IL-6 or IL-8 levels. These
      results suggest that IL-6, IL-8 and TNF-alpha may be relevant in the
      pathophysiology of periodontitis, and the measurement of these cytokines may be
      beneficial in the identification of patients with periodontitis.

PMID- 24137278
TI  - Evaluation of conservative treatment and timing of surgical intervention for mild
      forms of cervical spondylotic myelopathy.
AB  - The optimal management approach for patients with mild forms of cervical
      spondylotic myelopathy (MCSM) has not been well established. The aim of the
      present study was to investigate the outcome of conservative treatment, identify
      prognostic factors and provide evidence for the timing of surgical intervention.
      A total of 90 patients with MCSM attending hospital between February 2007 and
      January 2009 were prospectively enrolled. Initially, all patients received
      conservative treatment and were followed up periodically. When a deterioration in
      myelopathy was clearly identified, surgical treatment was conducted. Clinical and
      radiological factors correlating with the deterioration were examined, and final
      clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA)
      score. At the end of January 2012, follow-ups of >3 years were completed. Seventy
      eight patients were available for data analysis. Only 21 patients (26.9%)
      deteriorated and underwent surgery thereafter (group A), while the remaining 57
      patients (73.1%) were treated conservatively throughout (group B). Statistical
      analysis revealed that segmental instability and cervical spinal stenosis were
      adverse factors for the prognosis of conservative treatment. Although the JOA
      scores of the patients in group A declined initially, following surgical
      intervention, no significant differences were identified in JOA scores between
      the two groups at the time of the final follow-up (P=0.46). In summary,
      conservative treatment is effective in MCSM patients. Patients with segmental
      instability and cervical spinal stenosis have a tendency to deteriorate, but
      conservative treatment remains the recommendation for the first action. If the
      myelopathy deteriorates during conservative treatment, timely surgical
      intervention is effective.

PMID- 24137279
TI  - Combined use of hydration and alprostadil for preventing contrast-induced
      nephropathy following percutaneous coronary intervention in elderly patients.
AB  - Contrast-induced nephropathy (CIN) is a complex syndrome of acute kidney injury
      that follows exposure to intravascular contrast media. Although a series of
      preventive measures have been developed, CIN remains a major challenge
      encountered in elderly patients by interventional cardiologists. No data are
      currently available concerning the potential effects of the combined use of
      hydration and alprostadil in the prevention of CIN following percutaneous
      coronary intervention (PCI) in elderly patients. Therefore, the aim of the
      present study was to investigate the ability of a combination of hydration and
      alprostadil to prevent CIN following PCI in elderly patients. From June 1, 2010
      to January 31, 2012, 85 elderly patients undergoing PCI were included in the
      present study. The included patients were randomly allocated into three groups:
      the control (22 cases), hydration (28 cases) and hydration + alprostadil (35
      cases) group. Serum creatinine (SCr) levels were measured prior to PCI and then
      daily for 3 days following PCI. Creatinine clearance (Ccr) was also calculated.
      Following investigation of the incidence of CIN, a significant decline in Ccr was
      observed in the control group but not in the hydration + alprostadil group after
      PCI. The reduction in the level of Ccr from baseline in the hydration +
      alprostadil group was the smallest among the three groups. Moreover, the highest
      incidence of CIN was in the control group (6 cases, 27.27%), followed by the
      hydration group (3 cases, 10.71%) and the hydration + alprostadil group (1 case,
      2.86%). Therefore, the combined use of hydration and alprostadil significantly
      reduces the incidence of CIN in elderly patients undergoing PCI. Hydration and
      alprostadil are suggested to act synergistically to protect renal function. In
      conclusion, the combined use of hydration and alprostadil is more effective in
      the prevention of CIN in elderly patients undergoing PCI compared with hydration
      alone.

PMID- 24137280
TI  - Combined treatment with FK506 and nerve growth factor for spinal cord injury in
      rats.
AB  - Following spinal cord injury in rats, FK506 is able to protect local nerve
      tissue, promote neural regeneration, reduce neuronal apoptosis and accelerate the
      recovery of spinal cord functions. Nerve growth factor (NGF) is important in the
      regulation of central and peripheral nerve cell regeneration, growth
      differentiation and functions. Previous studies have shown that FK506 and NGF
      exhibit a synergistic effect in the treatment of peripheral nerve injury;
      however, it remains unclear whether the synergistic effect is present in the
      treatment of spinal cord injury. In this study, we combined FK506 and NGF for the
      treatment of spinal cord injury in rats. The NF200 protein expression in rats
      with spinal cord injury was determined using immunohistochemical staining and
      NF200 mRNA expression levels were observed using the reverse transcription
      polymerase chain reaction method. The restoration of spinal cord functions was
      evaluated using the Basso, Beattie and Bresnahan score. The results demonstrated
      that the combined treatment significantly enhanced the expression of NF200 and
      improved spinal cord functions compared with the results of the single treatment.
      Our experimental observations indicated that FK506 and NGF exhibit a synergistic
      effect in the treatment of spinal cord injury in rats and that the combined
      treatment may effectively promote neural regeneration and functional recovery in
      rats following spinal cord injury.

PMID- 24137281
TI  - Effects of intravenous diltiazem in a rat model of experimental coronary
      thrombotic microembolism.
AB  - The aim of this study was to assess the feasibility of evaluating the therapeutic
      effects of intravenous diltiazem in a newly established rat model of coronary
      thrombotic micro-embolism (CME). CME was induced by injecting 0.199 ml saline
      containing 5 mg of automicrothrombotic particulates (~10 MUm) into the aorta of
      Sprague Dawley rats. The injection was carried out over 10 sec using a tuberculin
      syringe with a 28-gauge needle. The CME model rats were randomly divided into
      untreated (CME, n=38) and diltiazem-treated (CME+DIL, n=38) groups. Diltiazem (1
      mg/ml, 50 MUg/min/kg) was intravenously injected using an infusion pump through
      the tail vein for 175 min, 5 min following the injection of the
      automicrothrombotic particulates. Hemodynamic measurements, echocardiography and
      pathohistological examinations were performed at various time-points (3 h, 24 h
      and 7 and 28 days) postoperatively. Arteriolar thrombosis, multifocal myocardial
      necrosis, inflammatory cell infiltration with markedly increased myocardial tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) expression, reduced
      left ventricular (LV) systolic function and increased plasma von Willebrand
      factor (vWF), endothelin-1 (ET-1) and serum c-troponin I (c-TnI) levels
      (indicating vascular endothelial injury and myocardial necrosis) were observed in
      the CME model rats. These pathological responses in CME rats were partly
      attenuated by intravenous diltiazem treatment. The present CME model is suitable
      for evaluating the therapeutic effects of intravenous diltiazem; intravenous
      diltiazem treatment significantly improved cardiac function through alleviating
      inflammatory responses and microvascular thrombotic injury in this rat model of
      CME.

PMID- 24137282
TI  - Multiple myeloma with extramedullary plasmacytoma invading the skin and eyeballs
      following autologous stem cell transplantation: A case report.
AB  - In this study, the case of a 60-year-old female patient who presented with a
      subcutaneous mass in the lower right limb is described. The mass was confirmed as
      a plasmacytoma. The patient was diagnosed with multiple myeloma (MM) lambda type
      stage III international stage system (ISS) and received three cycles of a
      therapeutic PDT regimen (bortezomib, dexamethasone and thalidomide) and complete
      remission was achieved. Following a further two cycles of the PDT regimen, the
      patient proceeded to received a high-dose cyclophosphamide regimen combined with
      granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization.
      Fourteen months later, the patient received a high-dose therapy supported by
      autologous stem cell transplantation (auto-SCT). After six months, a subcutaneous
      mass was identified in the left side of the patient's neck and the mass gradually
      increased in size. The patient exhibited exophthalmos and loss of sight one month
      later. The masses in the neck and right eyelid of the patient were diagnosed as
      plasmacytomas. These results, combined with the results of bone marrow (BM)
      aspiration and protein electrophoresis with immunofixation electrophoresis
      revealed that the disease had relapsed. The patient received two cycles of a
      therapeutic CPADT regimen (cyclophosphamide, bortezomib, pharmorubicin,
      dexamethasone and thalidomide). The patient subsequently achieved complete
      remission again. The patient refused to continue receiving bortezomib and
      pharmorubicin for therapy and instead received four cycles of the therapeutic CTD
      regimen (cyclophosphamide, dexamethasone and thalidomide). Subsequently the
      patient received local radiotherapy for the masses in the eyes and neck. The
      patient remained stable after treatment following the initial relapse with a
      progression-free survival (PFS) time of eight months.

PMID- 24137283
TI  - Leg lymphedema caused by iliopectineal bursitis associated with destruction of a
      rheumatoid hip joint: A case report.
AB  - The present study describes a case of leg lymphedema due to iliopectineal
      bursitis associated with rheumatoid arthritis (RA), which was satisfactorily
      controlled by surgery and combination therapy with methotrexate (MTX) and
      tacrolimus. A 68-year-old male, who had a six-year history of RA, developed an
      iliopectineal bursa associated with destruction of the hip joint. The mass
      gradually increased in size, and there was swelling in his right lower extremity.
      The patient was subsequently hospitalized with increasing right hip pain and leg
      edema. A colorless transparent lymph fluid leaked from his leg, and leg
      lymphedema was thus diagnosed. The patient also had a 20-year history of
      myelodysplastic syndrome. Therefore, the extensive or total resection of the
      bursa was considered to be too invasive, so a partial bursal excision was
      performed via an anterior approach. Following the partial bursal excision, total
      hip arthroplasty (THA) was performed using the Hardinge approach. The leg
      lymphedema disappeared following the surgery, and the iliopectineal bursa was no
      longer enlarged. MTX and tacrolimus were postoperatively administered to strictly
      control the RA. The RA was subsequently well controlled, without any increases in
      the levels of inflammatory markers, such as C-reactive protein and matrix
      metalloproteinase-3. This case demonstrated that iliopectineal bursitis was
      resolved following THA, without complete excision of the intrapelvic bursa, and
      that strict RA control led to a good clinical course without recurrent
      inflammation of the bursa. Similar procedures may be beneficial in other patients
      contraindicated for resection of the entire bursa.

PMID- 24137284
TI  - Malposition of peripherally inserted central catheter: Experience from 3,012
      patients with cancer.
AB  - The aim of this study was to observe and analyze the causes of misplacement of
      peripherally inserted central catheters (PICCs) in patients with cancer. A total
      of 3,012 patients who underwent insertion of a PICC were reviewed from August
      2000 to March 2012. The locations of the tube tips were recorded by chest X-ray
      examination. Malposition of the PICC was observed in 237 cases (7.87%), with the
      most frequently occurring site of misplacement being the jugular vein, followed
      by the axillary vein. By taking different remedies, all the malpositioned PICCs
      were relocated back to the superior vena cava or subclavian vein. In order to
      ensure the safe usage of PICCs, strict placement guidelines, skilled and
      experienced healthcare professionals and the cooperation of the patient is
      necessary.

PMID- 24137285
TI  - Evaluation of the inflammatory response in a two-hit acute lung injury model
      using [18F]FDG microPET.
AB  - The aim of this study was to investigate whether a two-hit acute lung injury
      (ALI) model is better than a one-hit model in simulating ALI, and to evaluate the
      inflammatory response in the lungs in these two models using micro-positron
      emission tomography (microPET) with [18F]fluorodeoxyglucose (FDG). Sprague Dawley
      rats were divided into four groups; rats in the lipopolysaccharide (LPS; n=10)
      and LPS-HCl (n=10) groups were challenged by the intraperitoneal administration
      of 5 mg/kg LPS, while rats in the normal saline (NS; n=3) and HCl (n=10) groups
      received the same volume of normal saline solution. Sixteen hours following the
      administration, the rats in the HCl and LPS-HCl groups received an acid
      instillation (IT) of 0.5 ml/kg HCl (pH=1.2), while the rats in the remaining two
      groups received the same volume of normal saline solution. The mean arterial
      blood pressure (MAP) and blood gas concentrations were measured in all four
      groups. MicroPET was performed 4 h following HCl IT and the lungs were excised
      for histopathological examination. The rats in the LPS-HCl group exhibited a
      higher arterial PaO2 and a lower arterial PaCO2 compared with the rats in the
      remaining groups. The MAP decreased markedly in the LPS-HCl group, but remained
      stable in the LPS, HCl and NS groups. MicroPET results identified that the region
      of interest ratio in the LPS-HCl group (9.00+/-1.41) was significantly higher
      compared with those in the LPS (4.01+/-0.60) and HCl (3.33+/-0.55) groups
      (P<0.01). In addition, histological examination showed that the mean lung injury
      score in the LPS-HCl group (12.70+/-0.95) was significantly higher compared with
      those in the HCl (8.40+/-1.26) and LPS (7.00+/-0.82) groups (P<0.01). The present
      study demonstrates that LPS pretreatment significantly magnifies and prolongs the
      inflammatory response to subsequent acid IT in the lungs. Moreover, it is simpler
      to induce ALI using the two-hit model than with the one-hit model, and [18F]FDG
      microPET is a useful tool for evaluating the inflammatory reaction during ALI.

PMID- 24137286
TI  - Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth
      muscle cell proliferation and migration via the MAPK signaling pathway.
AB  - An imbalance in the proliferation and migration of vascular smooth muscle cells
      (VSMCs) is significant in the onset and progression of vascular diseases,
      including arteriosclerosis and restenosis subsequent to vein grafting or coronary
      intervention. Rosuvastatin, a selective inhibitor of hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase, has pharmacological properties including the
      ability to reduce low-density lipoprotein-cholesterol (LDL-C) and very low
      density lipoprotein-cholesterol (VLDL-C) levels, slow atherosclerosis progression
      and improve coronary heart disease outcomes. However, little is known concerning
      the molecular mechanism by which rosuvastatin affects vascular cell dynamics. In
      this study, we studied the inhibitory role of rosuvastatin on platelet-derived
      growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, as well as
      the molecular mechanisms involved. MTT data showed that rosuvastatin markedly
      inhibited the proliferation of PDGF-BB-induced VSMCs in a time-dependent manner.
      VSMCs are able to dedifferentiate into a proliferative phenotype in response to
      PDGF-BB stimulation; however, rosuvastatin effectively attenuated this phenotype
      switching. Moreover, we also showed that rosuvastatin significantly suppressed
      PDGF-BB-induced VSMC migration, which may be a result of its inhibitory effect on
      the protein expression of matrix metalloproteinase-2 (MMP2) and MMP9.
      Investigation into the molecular mechanisms involved revealed that rosuvastatin
      inhibited the mitogen-activated protein kinase (MAPK) signaling pathway by
      downregulating extracellular signal-regulated kinase (ERK) and p38 MAPK, although
      the phosphorylation level of c-Jun N-terminal kinase (c-JNK) was not altered
      following rosuvastatin treatment. In conclusion, the present study showed that
      rosuvastatin suppressed PDGF-BB-induced VSMC proliferation and migration,
      indicating that rosuvastatin has the potential to become a promising therapeutic
      agent for the treatment of atherosclerosis and restenosis.

PMID- 24137287
TI  - Preventative effect of Astragalus flavescens on hepatic fibrosis in rats and its
      mechanism of action.
AB  - The aim of this study was to investigate the preventative effect of Astragalus
      flavescens on hepatic fibrosis in rats and its mechanism of action. A total of 60
      rats were randomly divided into normal control, model control, high-dose
      treatment and low-dose treatment groups, and a hepatic fibrosis model was
      established. The high- and low-dose treatment groups were treated with 2 g/100 g
      and 0.5 g/100 g Astragalus flavescens, respectively, once a day. Eight weeks
      following the initiation of treatment, the liver specimens of the rats were
      stained and observed under a light microscope. Hepatic fibrosis indices,
      specifically, type III precollagen (PC III), type IV collagen (C IV), hyaluronic
      acid (HA) and laminin (LN), were detected. Furthermore, the expression and
      localization of the hepatic fibrosis-related factors transforming growth factor
      beta1 (TGF-beta1), connective tissue growth factor (CTGF) and platelet-derived
      growth factor-BB (PDGF-BB) were determined. The serum levels of hepatic fibrosis
      indices, and the liver tissue levels of hepatic fibrosis-related factors and
      collagen surface density in the model control group and the high- and low-dose
      treatment groups were significantly higher compared with those of the normal
      control group (P<0.05). In addition, the values in the two treatment groups were
      significantly lower compared with those of the model control group (P<0.05). The
      present study demonstrated that Astragalus flavescens effectively prevents
      hepatic fibrosis in rats. A possible mechanism for this is that it may reduce the
      expression levels of TGF-beta1, PDGF-BB and CTGF, thereby inhibiting the
      activation of hepatic stellate cells and specifically blocking the signal
      transduction pathway of hepatic fibrosis.

PMID- 24137288
TI  - Evaluation of eye irritation by S-(-)-10,11-dihydroxyfarnesic acid methyl ester
      secreted by Beauveria bassiana CS1029.
AB  - The aim of this study was to investigate whether S-(-)-10,11-dihydroxyfarnesic
      acid methyl ester produced by cell subtype Beauveria bassiana CS1029 causes acute
      toxicity when used for cosmetic purposes by performing an eye irritation test.
      New Zealand white (NZW) rabbits were treated with a 100 mg/dose of S-(-)-10,11
      dihydroxyfarnesic acid methyl ester according to standard procedure guidelines.
      No significant changes in terms of ocular lesions of the cornea, turbidity of the
      cornea, swelling of the eyelid or ocular discharge were observed in the methyl
      ester-treated groups, while sodium dioctyl sulfosuccinate, a positive control,
      caused severe toxicity. The anatomical and pathological observations indicate
      that the methyl ester produced by Beauveria bassiana CS1029 did not induce eye
      irritation in the lenses of the rabbits. The data suggest that the methyl ester
      evaluated in this study has promising potential as a cosmetic ingredient that
      does not irritate the eye.

PMID- 24137289
TI  - Comparison between the pharmacokinetics of meranzin hydrate in a rat model of
      chronic depression and in controls following the oral administration of Chaihu
      Shugan-San.
AB  - Previous studies have shown that meranzin hydrate (MH) may be beneficial in
      depressive disorders. However, to the best of our knowledge, the pharmacokinetic
      characteristics of MH in depression have not previously been investigated.
      Chronic mild stress (CMS) in rats is used as a model of depression. The present
      study was designed to evaluate and compare the pharmacokinetics of MH in CMS and
      control rats following the oral administration of Chaihu-Shugan-San (CSS). Rats
      were randomly divided into CMS and control groups and blood samples were obtained
      following the oral administration of CSS. The quantification of MH levels in the
      plasma for pharmacokinetic study was achieved using a simple and rapid ultra
      performance liquid chromatography with photodiode array (UPLC-PDA) method.
      Following the oral administration of CSS to CMS rats and controls, the maximum
      plasma concentration (Cmax) of MH was 58.66+/-6.64 and 57.54+/-12.67 ng/ml at
      108.00+/-26.83 and 54.00+/-8.22 min, respectively. Compared with the value of the
      area under the concentration-time curve (AUC)0-1440 in control rats (19,896.76+/
      1,041.95 MUg.min/l), the AUC0-1440 value was reduced in CMS rats (18,401.32+/
      4332.65 MUg.min/l). There were no significant differences in the majority of the
      pharmacokinetic parameters of MH, including the values for Cmax, AUC0-1440,
      clearance rate (CL/F) and mean residence time (MRT0-1440), between the CMS rats
      and the controls. However, the pharmacokinetic parameters showed that CMS
      accelerated the absorption of MH in rats following the oral administration of
      CSS.

PMID- 24137290
TI  - Aging-associated changes in L-type calcium channels in the left atria of dogs.
AB  - Action potential (AP) contours vary considerably between the fibers of normal
      adult and aged left atria. The underlying ionic and molecular mechanisms that
      mediate these differences remain unknown. The aim of the present study was to
      investigate whether the L-type calcium current (ICa.L) and the L-type Ca2+
      channel of the left atria may be altered with age to contribute to atrial
      fibrillation (AF). Two groups of mongrel dogs (normal adults, 2-2.5 years old and
      older dogs, >8 years old) were used in this study. The inducibility of AF was
      quantitated using the cumulative window of vulnerability (WOV). A whole-cell
      patch-clamp was used to record APs and ICa.L in left atrial (LA) cells obtained
      from the two groups of dogs. Protein and mRNA expression levels of the a1C
      (Cav1.2) subunit of the L-type calcium channel were assessed using western
      blotting and quantitative PCR (qPCR), respectively. Although the resting
      potential, AP amplitude and did not differ with age, the plateau potential was
      more negative and the APD90 was longer in the aged cells compared with that in
      normal adult cells. Aged LA cells exhibited lower peak ICa.L current densities
      than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein
      expression levels in LA cells were decreased in the aged group compared with
      those in the normal adult group. The lower AP plateau potential and the decreased
      ICa.L of LA cells in aged dogs may contribute to the slow and discontinuous
      conduction of the left atria. Furthermore, the reduction of the expression levels
      of Cav1.2 with age may be the molecular mechanism that mediates the decline in
      ICa.L with increasing age.

PMID- 24137291
TI  - Triple pathology in patients with temporal lobe epilepsy: A case report and
      review of the literature.
AB  - The coexistence of three intracranial lesions related to epileptic pathogenesis
      is known as 'triple pathology' and has rarely been reported. In this study we
      report a case of temporal lobe epilepsy (TLE) with the coexistence of hippocampal
      sclerosis (HS), focal cortical dysplasia (FCD) and ganglioglioma in the temporal
      lobe. A 29-year-old male who had experienced recurrent seizures for four years
      was admitted to hospital. Cerebral magnetic resonance imaging (MRI) was conducted
      and T2-weighted and fluid-attenuated inversion recovery sequence (FLAIR) images
      revealed a reduced hippocampal volume with an increased FLAIR signal on the right
      side and a slightly enlarged temporal horn, which are typical imaging findings
      for HS and FCD. The patient underwent resectioning of the right anterior temporal
      lobe, hippocampus and amygdala, in addition to the lesion located in the medial
      temporal lobe. Immunohistochemical analysis of the medial temporal lobe lesion
      confirmed a ganglioglioma (WHO grade I) in the medial temporal lobe. During the
      first eight months following surgery, the patient's seizures were controlled with
      zonisamide and phenytoin. Electroencephalogram (EEG) assessment post-surgery
      confirmed the absence of epileptic discharges. Based on a literature review and a
      detailed review of this case, we postulate two possible explanations for the
      pathogenesis of 'triple pathology': i) 'triple pathology' is a combination of
      pathological progression and occasionality; and ii) 'triple pathology' lesions
      have similar pathological origins.

PMID- 24137292
TI  - Artificial and bioartificial liver support systems for acute and acute-on-chronic
      hepatic failure: A meta-analysis and meta-regression.
AB  - Artificial and bioartificial liver support systems (LSSs) appear to be safe and
      effective in the treatment of acute and acute-on-chronic hepatic failure (AHF and
      AOCHF); however, individually published studies and previous meta-analyses have
      revealed inconclusive results. The aim of the present meta-analysis was to derive
      a more precise estimation of the benefits and disadvantages of artificial and
      bioartificial LSSs for patients with AHF and AOCHF. A literature search was
      conducted in the PubMed, Embase, Web of Science and Chinese Biomedical (CBM)
      databases for publications prior to March 1, 2013. Crude relative risks (RRs) or
      standardized mean differences (SMDs) with 95% confidence intervals (95% CI) were
      calculated using either the fixed effects or random effects models. Nineteen
      randomized controlled trials (RCTs) were included, which comprised a total of 566
      patients with AHF and 371 patients with AOCHF. The meta-analysis showed that
      artificial LSS therapy significantly reduced mortality in patients with AOCHF;
      however, it had no apparent effect on total mortality in patients with AHF. The
      results also indicated that the use of bioartificial LSSs was correlated with
      decreased mortality in patients with AHF. A significant reduction in the bridging
      to liver transplantation was observed in patients with AOCHF following artificial
      LSS therapy; however, similar results were not observed in patients with AHF.
      Patients with AHF and those with AOCHF showed significant reductions in total
      bilirubin levels following artificial LSS therapy. There were no significantly
      increased risks of hepatic encephalopathy or bleeding in either the patients with
      AHF or AOCHF following artificial or bioartificial LSS therapies. Univariate and
      multivariate meta-regression analyses confirmed that none of the factors
      explained the heterogeneity. The present meta-analysis indicated that artificial
      LSSs reduce mortality in patients with AOCHF, while the use of bioartificial LSSs
      was correlated with reduced mortality in patients with AHF.

PMID- 24137293
TI  - Human adipose-derived stem cell adipogenesis induces paracrine regulation of the
      invasive ability of MCF-7 human breast cancer cells in vitro.
AB  - The aim of this study was to determine the effects of paracrine regulation on the
      invasive ability of MCF-7 human breast cancer cells through human adipose-derived
      stem cell (hADSC) adipogenesis. hADSC differentiation of the third and fourth
      passages of cells was induced in different induction media: osteogenic,
      adipogenic and chondrogenic. Transwell migration assays in the differently
      conditioned media, flow cytometry, enzyme-linked immunosorbent assay and western
      blot analysis for selected cytokines were performed. The flow cytometric analysis
      demonstrated positive expression of CD29, CD44 and CD105, while expression of
      CD34 and CD45 was not identified. The transwell migration assay showed that the
      invasive ability of MCF-7 cells was significantly enhanced during hADSC
      adipogenesis. hADSCs exerted a significantly positive effect on the invasive
      activity of MCF-7 cells during adipo-genesis. The results indicate that the high
      expression levels of activating protein 2 (aP2) in MCF-7 and adipocytes induced
      for 12 days may be associated with cell growth, invasion and metastasis.
      Peroxisome proliferator-activated receptor gamma may be involved in fatty
      syntheses during adipogenic initiation and following adipogenic differentiation,
      possibly acting as a protection factor resulting in cell maturation and
      differentiation. This study also demonstrated that the expression of vascular
      endothelial growth factor was repressed by hADSCs, while that of matrix
      metalloproteinase-2 and urokinase-type plasminogen activator was increased to a
      significant level.

PMID- 24137294
TI  - Cervical spondylotic myelopathy with vitamin B12 deficiency: Two case reports.
AB  - Although it has been observed that a vitamin B12 (VB12) deficiency may lead to
      defects in the nervous system, there is a lack of studies elucidating whether
      VB12 has a role in the pathogenesis of cervical spondylotic myelopathy (CSM). The
      present study describes two cases of CSM observed in the clinic, where the
      patients presented with common characteristics of the typical clinical symptoms;
      however, T2-weighted magnetic resonance imaging examinations revealed that
      although the degree of spinal cord compression was not serious, the spinal cord
      exhibited significant high signal changes. At the same time, the serum VB12
      levels of the two patients were lower compared with those of normal controls. The
      symptoms of the patients improved following anterior cervical decompression
      surgery and VB12 replacement therapy. The incidence of CSM in the two patients
      may have been correlated with a lack of VB12. Therefore, it is recommended that
      the serum VB12 levels are checked in cases of CSM where the standard imaging and
      clinical manifestations do not fully match.

PMID- 24137295
TI  - Establishing a model of middle cerebral artery occlusion in rabbits using
      endovascular interventional techniques.
AB  - This study aimed to establish a minimally invasive and easily controllable focal
      cerebral ischemia model in rabbits using interventional techniques for use in the
      study of thrombolytic treatment, and to evaluate the feasibility and
      reproducibility of the technique. Under the guidance of digital subtraction
      angiography (DSA), focal cerebral infarction was produced by blocking the middle
      cerebral artery with arterial emboli to establish a rabbit brain artery occlusion
      model. DSA and diffusion magnetic resonance imaging (MRI) were used to observe
      the cerebral vascular obstruction infarction, while modified Bederson scoring was
      used to evaluate the neurological impairment. The animals were sacrificed 24 h
      after surgery and brain tissues were stained with 2,3,5-triphenyltetrazolium
      chloride (TTC) to evaluate the occlusion of the middle cerebral artery and
      pathological changes. The rabbit brain artery occlusion models were successfully
      established and the animals survived following embolization. Cerebral infarctions
      were observed in the brains of all animal models. The focal cerebral infarction
      rabbit model established by vascular interventional techniques is simple,
      minimally invasive and reliable, and may be used for early diagnosis of cerebral
      infarction and clinical thrombolysis studies.

PMID- 24137296
TI  - Effects of cytokine-induced killer cell treatment combined with FOLFOX4 on the
      recurrence and survival rates for gastric cancer following surgery.
AB  - The aim of this study was to investigate the effects of cytokine-induced killer
      (CIK) cell treatment combined with FOLFOX4 on the recurrence and survival rates
      of patients suffering from gastric cancer following surgery. A total of 98
      patients with gastric cancer, who were surgically treated from June 2010 to June
      2012, were divided into two groups: 47 patients, who underwent FOLFOX4 treatment
      alone, served as the control group, while the remaining 51 patients received
      FOLFOX4 in combination with CIK cell immunotherapy and served as the observation
      group. The immune functions, recurrence and survival rates were estimated and
      compared between the two groups. No significant differences were observed between
      the immune functions of the patients prior to treatment compared with the
      functions following treatment (P>0.05). However, the immune functions of the
      patients were improved following FOLFOX4 treatment in combination with CIK cell
      immunotherapy compared with the functions of the patients who received FOLFOX4
      treatment alone (P<0.05). The gastric cancer recurrence rates of the patients in
      the observation group were significantly lower compared with those of the
      patients in the control group (5.9 versus 25.5, 17.6 versus 36.2 and 23.5 versus
      48.9% after 1, 2 and 3 years, respectively; P<0.05). In addition, the survival
      rates of the patients with gastric cancer in the observation group were
      significantly enhanced compared with those of the control group, as assessed by
      log-rank test analysis (98.0 versus 93.6, 92.2 versus 78.7 and 72.5 versus 59.6%
      after 1, 2 and 3 years, respectively; P<0.05). It may be concluded that FOLFOX4
      combined with CIK cell treatment has significant benefits for patients suffering
      from gastric cancer, compared with FOLFOX4 treatment alone.

PMID- 24137297
TI  - Use of a calcium tracer to detect stone increments in a rat calcium oxalate
      xenoplantation model.
AB  - The majority of urinary stones have been observed to grow by circular increments
      in the clinic and in animal studies. However, the mechanism of stone formation
      has not yet been elucidated. Marking the stone at specific time-points during the
      growth of the stone is likely to enable the clarification of the mechanisms
      behind lithogenesis. The objective of this study was to evaluate the role and
      efficacy of calcium-tracing fluorescence in the labeling of stone lamination in a
      rat calcium oxalate xenoplantation model. In the rat calcium oxalate
      xenoplantation model, human renal stone particles, extracted by percutaneous
      nephrolithotomy, were xenoplanted into the bladders of Wistar rats in a sterile
      manner. The rats received 1% ethylene glycol in their drinking water, starting
      from the day following the stone xenoplantation. Two weeks subsequent to this,
      three calcium-tracing fluorochromes, alizarin complexone, calcein and xylenol
      orange were administered by intraperitoneal injection. The newly-formed bladder
      stones were cut into slices and examined using light and fluorescence microscopy.
      The newly-formed bladder stones had a large variance in size, and circular
      increments were observed in the sections of the stones. The stones were
      successfully labeled with calcein and alizarin complexone, although calcein
      labeling provided superior results. However, the use of xylenol orange did not
      result in clear labeling. The calcium-tracing fluorochromes, calcein and alizarin
      complexone may be effectively used to label stone lamination in rat models.

PMID- 24137298
TI  - Dual-source computed tomography for evaluating coronary stenosis and left
      ventricular function.
AB  - This study aimed to evaluate the correlation between coronary stenosis and left
      ventricular function using dual-source computed tomography (DSCT). DSCT coronary
      angiography (CAG) was performed on 66 patients with coronary disease and 36
      healthy volunteers. The degree of coronary stenosis, end-diastolic volume (EDV),
      end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and
      myocardial mass (MM) were measured for the left ventricle. These values were
      compared with the results obtained by echocardiography (ECHO) and selective CAG,
      which were both adopted as controls. The diagnoses of coronary stenosis based on
      DSCT CAG and those based on selective CAG were not significantly different
      (P>0.05). Similarly, the values of EDV, ESV, SV or EV measured by DSCT CAG were
      not significantly different from thoses obtained by ECHO (P>0.05). However,
      significant differences were observed in the ESV, EF and SV of the severe
      stenosis group compared with the moderate and mild stenosis groups (both P<0.05).
      The values of EDV and MM significantly varied between the mild, moderate and
      severe stenosis groups (P<0.05). DSCT CAG is a highly accurate and highly
      reproducible method for evaluating the preliminary changes in cardiac function
      based on the variations of coronary stenosis. Significant changes were detected
      in the EDV and MM of the moderate stenosis group and in all parameters of the
      severe stenosis group.

PMID- 24137299
TI  - Optimization of the method for the culture of melanocyte precursors from hair
      follicles and their activation by 1,25-dihydroxyvitamin D3.
AB  - The melanocytes in vitiligo repigmentation are derived predominantly from
      melanocyte precursors (MPs) present in the outer root sheath (ORS) of hair
      follicles. The methods currently used for culturing MPs are unstable, and the
      cultured cells have the capacity to produce melanin. These factors are
      problematic when conducting in vitro studies to investigate the mechanism of
      repigmentation. Although 1,25-dihydroxyvitamin D3 (VID) has been demonstrated to
      be highly effective in the treatment of vitiligo in the clinic, its precise mode
      of action has yet to be elucidated. In the present study, the method for the
      culture of MPs from the ORS of hair follicles was optimized and the ability of
      VID to activate MPs was investigated. The results suggested that the MPs cultured
      using the optimized method mainly exhibited bipolar morphology. The cells
      proliferated well and were negative for 3,4-dihydroxy-L-phenylalanine (DOPA)
      staining. Transmission electron microscopy revealed that the cytoplasm of the MPs
      contained numerous stage I and stage II melanosomes; however, stage III and IV
      melanosomes were not observed. Following VID treatment, the MPs showed increased
      dendritic morphology, the cells stained positive for DOPA and stage III and IV
      melanosomes appeared in the cells. Western blotting revealed that microphthalmia
      associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related
      protein-1 (TRP-1) and TRP-2 were expressed in the MPs and that VID increased the
      expression levels of MITF, TYR and TRP-1. However, the levels of MITF, TYR and
      TRP-1 in the MPs prior to and following VID treatment were significantly lower
      compared with those in cultured epidermal melanocytes, while the levels of TRP-2
      in these three groups were not significantly different. Subsequent to VID
      treatment, the TYR activity in the MPs increased significantly, as did the
      corresponding melanin levels. In conclusion, the present study successfully
      optimized the method for MP culture. The MPs demonstrated no significant TYR
      activity or melanin synthesis; therefore, the MP cultures exhibited the features
      of MPs in vivo. In addition, VID significantly promoted the differentiation of
      MPs.

PMID- 24137300
TI  - Behavioral and biochemical effects of a formulation of the traditional Chinese
      medicine, Kai-Xin-San, in fatigued rats.
AB  - The present study was designed to evaluate the anti-fatigue activity and the
      behavioral and biochemical effects of Kai-Xin-San (KXS) extracts on fatigued
      rats. The rats were randomly divided into six groups: untreated control (UC),
      running control (RC), RC treated with 13 mg/kg/day modafinil and RC treated with
      KXS at dosages of 125, 250 and 500 mg/kg/day, respectively. The treatments were
      administered orally. Anti-fatigue activity was assessed using the treadmill
      running test and serum biochemical parameters were determined using an
      autoanalyzer and commercially available kits. Furthermore, the standardization of
      the KXS extracts was ensured using a high-performance liquid chromatography
      (HPLC)-fingerprint. The extracts were shown to increase exhaustive running time
      in the treadmill running test and reverse the fatigue-induced reduction in
      hepatic/muscle glycogen and testosterone, in addition to reducing the lactate
      dehydrogenase (LDH), serum urea nitrogen (SUN), blood lactic acid (BLA) and beta
      endorphin levels in the serum of the fatigued rats. Moreover, the extracts
      enhanced superoxide dismutase (SOD) activity and decreased the malondialdehyde
      (MDA) levels in the serum of the fatigued rats. The results of this preliminary
      study indicated that KXS exhibits anti-fatigue activity. This was reflected in
      the effects on the biochemical markers for fatigue.

PMID- 24137301
TI  - Therapeutic effects of autologous hematopoietic stem cell transplantation in
      multiple myeloma patients.
AB  - The present study aimed to evaluate the effect of autologous hematopoietic stem
      cell transplantation (ASCT) on the response and outcome of patients with multiple
      myeloma (MM) and to analyze the factors influencing the prognosis of the disease.
      Retrospective analysis was performed in 27 patients with MM who had been treated
      by ASCT (ASCT group) and 28 patients treated with combined chemotherapy only (non
      ASCT group) from May 2004 to August 2011. The impact on the depth of response,
      progression-free survival (PFS) and overall survival (OS) times, as well as
      associated prognostic factors of patients with MM, were analyzed. All patients
      successfully underwent hematopoietic reconstruction without transplantation
      related mortality. The complete remission (CR) rate of patients in the ASCT group
      significantly increased from 25.9% (7/27) before ASCT to 70.4% (19/27) following
      ASCT (P<0.01). The probability of OS for 5 years was 52.2% for the patients in
      the ASCT group and 33.1% for those in the non-ASCT group (P>0.05). Univariate
      analysis in the ASCT group demonstrated that maintenance and consolidation
      therapies were associated with significant increases in PFS (P=0.01) and OS
      (P<0.01) times. The present study demonstrated that ASCT further increases the CR
      rate, prolongs PFS time and potentially increases the OS time. Incorporation of
      these novel agents, including the protea-some inhibitor bortezomib and the
      immunomodulatory drugs thalidomide and lenalidomide, into the induction,
      consolidation and maintenance phases has optimized the anti-myeloma activity of
      ASCT.

PMID- 24137302
TI  - Removal of 3-methylindole by lactic acid bacteria in vitro.
AB  - 3-Methylindole (3MI) is a substance with an unpleasant odor that is found in
      intact male pigs and is known to negatively affect consumers of pork. The growth
      of four strains of lactic acid bacteria [Lactobacillus brevis 1.12 (L. brevis
      1.12), L. plantarum 102, L. casei 6103 and L. plantarum ATCC8014] in incubation
      medium with 3MI was studied. The four strains were tested for their ability to
      remove 3MI from the medium. The growth of L. brevis 1.12 remained steady as the
      levels of 3MI increased 3MI from 0.2 to 1.0 MUg/ml. The 3MI removal ability of L.
      brevis 1.12 was the strongest among the four strains, and the highest removal
      rate was 65.35+/-0.3% in 1 ml incubation medium containing 1.0 MUg/ml 3MI for 120
      h. Furthermore, the supernatant fluid of the fermentation broth of L. brevis 1.12
      had a stronger ability to remove 3MI than cell pellets and cell extracts and the
      removal rate was 14.4+/-0.3% in 24 h. Further results indicate that the mode of
      removal of 3MI was not through the physical binding of cells by L. brevis 1.12.

PMID- 24137303
TI  - Rosiglitazone attenuates the severity of hyperlipidemic severe acute pancreatitis
      in rats.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand regulates
      adipocyte differentiation and insulin sensitivity, and exerts antihyperlipidemic
      and anti-inflammatory effects. However, the mechanisms by which PPAR-gamma
      ligands affect hyperlipidemia with severe acute pancreatitis (SAP) have not been
      fully elucidated. The present study investigated the effects of rosiglitazone, a
      PPAR-gamma ligand, on hyperlipidemia with SAP in a rat model. The hyperlipidemia
      was induced with a high-fat diet and SAP was induced by the administration of
      sodium taurocholate (TCA). The hyperlipidemia was shown to aggravate the severity
      of the sodium taurocholate-induced SAP. However, rosiglitazone demonstrated
      significant antihyperlipidemic and anti-inflammatory effects in the rats with
      high-lipid diet-induced hyperlipidemia and SAP.

PMID- 24137304
TI  - Role of the NT-proBNP level in the diagnosis of pediatric heart failure and
      investigation of novel combined diagnostic criteria.
AB  - The aim of this study was to investigate the modified Ross criteria score and the
      diagnostic cut-off level for plasmatic amino-terminal pro-brain natriuretic
      peptide (NT-proBNP) in the diagnosis of pediatric heart failure, by analyzing the
      receiver operating characteristic (ROC) curve. The plasma NT-proBNP level was
      measured in 80 children diagnosed with heart failure according to the modified
      Ross criteria, 80 children with non-cardiogenic dyspnea and 80 healthy children.
      The NT-proBNP levels were then compared using an F-test. The cut-off score for
      heart failure in the modified Ross criteria and the diagnostic cut-off level for
      plasmatic NT-proBNP in pediatric heart failure were determined by ROC curve
      analysis. The results demonstrated that the NT-proBNP level was markedly
      increased in 76 of the 80 children with heart failure, and the correlation with
      the modified Ross criteria was 95%. Based on ROC curve analysis, the diagnosis of
      pediatric heart failure was most accurate when the modified Ross criteria score
      was >=4 and the plasmatic NT-proBNP level was >=598 ng/l. The NT-proBNP level was
      normal (0-300 ng/l) in the children with non-cardiogenic dyspnea and the healthy
      children. Significant differences were observed in the comparison of the three
      groups (P<0.01). In conclusion, a NT-proBNP level of >=598 ng/l, combined with a
      modified Ross criteria score >=4, is highly diagnostic of heart failure in
      children.

PMID- 24137305
TI  - Synergistic effect of clinically used antibiotics and peptide antibiotics against
      Gram-positive and Gram-negative bacteria.
AB  - Ribosomally synthesized (natural) peptides demonstrate antimicrobial potency and
      may represent a novel therapeutic approach for the treatment of infections. The
      aim of the present study was to investigate the interaction between polycationic
      peptides and clinically used antimicrobial agents in the treatment of clinical
      isolates of Gram-positive and Gram-negative aerobic bacteria in vitro, using the
      microbroth dilution method. The combination studies demonstrated synergies
      between ranalexin and polymyxin E, doxycycline and clarithromycin. Similarly,
      magainin II was demonstrated to be synergistic with ceftriaxone, amoxicillin
      clavulanate, ceftazidime, meropenem, piperacillin and beta-lactam antibiotics.
      Buforin II, cecropin P1 and indolicidin were not observed to be synergistic with
      the clinically used antibiotics, but demonstrated additive effects with them.
      Notably, no antagonistic effects were identified in all the combinations
      examined.

PMID- 24137306
TI  - Application of real-time B-mode ultrasound in posterior decompression and
      reduction for thoracolumbar burst fracture.
AB  - This study aimed to investigate the role of real-time B-mode ultrasound in
      posterior decompression and reduction and to observe the signal changes in spinal
      cord blood flow in a thoracolumbar burst fracture (TBF). Between February 2004
      and December 2008, 138 patients with TBF were divided into group A (108 cases)
      and group B (30 cases). In group A, under the assistance of real-time B-mode
      ultrasound, posterior decompression and fracture piece reduction were performed,
      and we observed the signal changes in spinal cord blood flow. In group B,
      posterior fenestration was combined with pushing the fracture piece into the
      fractured vertebral body using an L-shaped operative tool. Presurgical and
      postsurgical recovery of neurological function was evaluated according to
      American Spinal Injury Association (ASIA) standards, and the range of spinal
      decompression was determined by measuring the proportion of encroached fracture
      piece in the spinal canal (spinal stenosis rate) on the computed tomography (CT)
      image. In group A, 12 patients had a grade A spinal injury according to the
      Frankel grading system, and there were six cases without neurological recovery.
      In the other patients, neurological function increased by 1-3 grades. There were
      no aggravated spinal cord injuries or other serious complications. In group B,
      three patients were categorized as grade A and there were two cases without
      neurological recovery. In the other patients, neurological function increased by
      1-3 grades. In groups A and B, the postsurgical spinal stenosis rate was
      significantly lower than the presurgical stenosis rate (P<0.05). The postsurgical
      spinal stenosis rate in group B was significantly higher compared with group A
      (P<0.05). There was no significant difference in neurological function recovery
      between the groups (P>0.05). Real-time B-mode ultrasound is an effective method
      for posterior decompression and reduction and to observe signal changes in spinal
      cord blood flow in TBF.

PMID- 24137307
TI  - Immunostimulatory effect of a composition isolated from white peony root oral
      liquid in the treatment of radiation-induced esophagitis.
AB  - The aim of this study was to explore the immune repairing effect of a composition
      isolated from white peony root oral liquid (cWPROL), a traditional Chinese herbal
      composition, in the treatment of experimental radiation-induced esophagitis in
      rats. A total of 128 Wistar rats were randomly divided into eight groups,
      irradiated with 43 Gy 60Co gamma-rays to induce esophagitis and treated by
      different methods. Flow cytometry, hematological analysis and immune nephelometry
      were used to detect the absolute numbers and percentages of CD3+, CD4+ and CD8+ T
      lymphocytes, numbers and classification of leukocytes, and the levels of IgG and
      complement C3 in the peripheral blood of the rats at each experimental time
      point. Following irradiation, the total number of leukocytes, absolute numbers
      and percentages of CD3+, CD4+ and CD8+ T lymphocytes, and levels of IgG and
      complement C3 in the peripheral blood of the rats were decreased. Furthermore,
      the total numbers of leukocytes, absolute numbers and percentages of CD3+, CD4+
      and CD8+ T lymphocytes, and levels of IgG and complement C3 in the peripheral
      blood were higher in the administered with cWPROL by intra-esophageal perfusion
      compared with those in the untreated irradiated groups, but lower in the groups
      treated with a mixture of lidocaine hydrochloride, dexamethasone sodium phosphate
      and gentamicin sulfate. This study suggested that cWPROL is able to repair the
      impaired cellular and humoral immunity of rats with radiation-induced
      esophagitis.

PMID- 24137308
TI  - Catheter-directed thrombolytic therapy combined with angioplasty for hepatic vein
      obstruction in Budd-Chiari syndrome complicated by thrombosis.
AB  - The aim of this study was to assess the efficacy and safety of catheter-directed
      thrombolysis combined with angioplasty in the treatment of hepatic vein
      obstruction in Budd-Chiari syndrome (BCS) complicated by thrombosis. In 14 cases
      of BCS, the patients with hepatic vein obstruction complicated by thrombosis who
      underwent catheter-directed urokinase thrombolysis, balloon dilatation and/or
      stent placement were followed up with an ultrasound examination of the liver.
      Among the 13 cases of successful treatment, one hepatic vein was recanalized in
      12 patients (right hepatic vein, seven cases; left hepatic vein, three cases;
      middle hepatic vein, one case and accessory hepatic vein, one case) and two
      hepatic veins (right and left) were recanalized in one patient without serious
      complications, such as bleeding and pulmonary embolism. There was one patient in
      whom the treatment was unsuccessful. During an average follow-up period of 24.8+/
      19.6 months, hepatic vein restenosis was observed in one patient in the sixth
      month after opperation; however, a successful result was obtained following a
      second balloon dilatation. The remaining 12 patients did not demonstrate any
      recurrence of restenosis or thrombosis. Catheter-directed thrombolysis combined
      with angioplasty was observed to be an effective and safe method for the
      treatment of hepatic vein obstruction in BCS complicated by thrombosis.

PMID- 24137309
TI  - Photoprotective and immunoregulatory capacity of ginsenoside Rg1 in chronic
      ultraviolet B-irradiated BALB/c mouse skin.
AB  - The aim of this study was to investigate the photoprotective and immunoregulatory
      capacities of ginsenoside Rg1 in skin irradiated by chronic ultraviolet B (UVB)
      and to verify the potential mechanisms of action. BALB/c mice were pretreated
      with a topical application of ginsenoside Rg1 and irradiated with different doses
      of UVB daily for 30 consecutive days. Following chronic UVB irradiation, there
      were significant pathological changes in the skin of the BALB/c mice, including
      hyperkeratosis, acanthosis, sponge-like edematization and sunburn occurring in
      the epidermis, while edema, telangiectasis and inflammatory cell infiltration
      were observed in the papillary layer of the dermis. Treatment with ginsenoside
      Rg1 was able to reduce such changes induced by UVB irradiation. The number of p53
      protein-positive stained cells following UVB irradiation was also observed by
      immunohistochemical analysis. Ginsenoside Rg1 downregulated the p53 protein
      expression induced by UVB irradiation, leading to reductions of 69.50, 23.53 and
      12.93% at doses of 30, 60 and 120 mJ/cm2, respectively. Using reverse
      transcription polymerase chain reaction (RT-PCR), reductions in the levels of
      interferon (IFN)-gamma mRNA expression were detected following UVB exposure;
      reductions of 19.6, 36.3 and 39.6% were observed following UVB irradiation at
      doses of 30, 60 and 120 mJ/cm2, respectively. The interleukin (IL)-10 mRNA
      expression levels increased by 40.1, 71.0 and 89.4% and the tumor necrosis factor
      (TNF)-alpha mRNA expression levels increased by 36.4, 18.4 and 8.6% following UVB
      irradiation at doses of 30, 60 and 120 mJ/cm2, respectively. However,
      pretreatment with ginsenoside Rg1 was observed to markedly attenuate the UVB
      irradiation-induced effects on the mRNA expression levels of the three cytokines.
      The topical application of ginsenoside Rg1 was able to protect the irradiated
      skin from UVB injury and reduce UVB-induced p53 protein expression. Ginsenoside
      Rg1 also demonstrated a potential regulatory effect on the UVB-induced local
      expression of the mRNA of the cytokines IFN-gamma, IL-10 and TNF-alpha, which may
      be important in its immunoregulatory and inflammatory mechanisms.

PMID- 24137310
TI  - Effects of heat stress on the expression of the coxsackievirus and adenovirus
      receptor in mouse skin keratinocytes.
AB  - The aim of this study was to investigate the effects of heat stress on the
      expression of the coxsackievirus and adenovirus receptor (CAR) in mouse skin
      keratinocytes. Twenty BALB/c mice were randomly divided into two groups: the sham
      heat (control) and scald groups. Skin specimens were obtained 6 h after the
      treatments. Changes in the expression of CAR in skin keratinocyte samples were
      detected by immunohistochemistry, quantitative polymerase chain reaction and
      western blotting. In an in vitro assay, mouse skin keratinocytes were cultured
      and randomly divided into two groups: the normal control and heat stress groups.
      Six hours subsequently, the changes in CAR expression in the two groups were
      estimated by flow cytometry to determine the differences between the two groups.
      Heat stress significantly increased the expression of CAR in the mouse skin
      keratinocytes (P<0.05). The upregulation of CAR in mouse keratinocytes in burn
      wounds may be beneficial for restoring healing in organisms.

PMID- 24137311
TI  - Triple versus dual antiplatelet therapy for coronary heart disease patients
      undergoing percutaneous coronary intervention: A meta-analysis.
AB  - Coronary heart disease (CHD) is the leading cause of mortality worldwide.
      Previous studies have suggested that cilostazol-based triple antiplatelet therapy
      (TAT) may be more effective than conventional dual antiplatelet therapy (DAT) at
      improving the clinical outcomes of patients with CHD undergoing percutaneous
      coronary intervention (PCI). However, individually published results are
      inconclusive. The present meta-analysis evaluated controlled clinical studies to
      compare the clinical outcomes between TAT and DAT in patients with CHD undergoing
      PCI. Ten controlled clinical studies were included, with a total of 7,670
      patients with CHD undergoing PCI. The total number included 3,925 patients
      treated with DAT (aspirin and clopidogrel) and 3745 patients treated with TAT
      (addition of cilostazol to DAT). The crude odds ratio (OR) with a 95% confidence
      interval (CI) was calculated with either the fixed or random effects model. The
      meta-analysis results indicated that patients in the TAT group had a
      significantly lower rate of restenosis compared with that of the DAT group
      (OR=0.59, 95% CI: 0.45-0.77; P<0.001). The rate of major adverse cardiac events
      (MACE) and target lesion revascularization (TLR) in the TAT group were
      significantly lower compared with those in the DAT group (MACE: OR=0.69, 95% CI:
      0.56-0.85, P<0.001; TLR: OR=0.61, 95% CI: 0.43-0.88, P=0.008). However, no
      significant differences between the TAT and DAT groups in terms of mortality
      rate, myocardial infarction, target vessel revascularization and stent thrombosis
      were observed. In conclusion, the results of the present meta-analysis indicated
      that the efficacy and safety of cilostazol-based TAT therapy is greater than that
      of conventional DAT therapy for patients with CHD undergoing PCI.

PMID- 24137312
TI  - Avascular necrosis of the femoral head due to the bilateral injection of heroin
      into the femoral vein: A case report.
AB  - In this study, we report a case of avascular necrosis of the femoral head (ANFH)
      caused by the bilateral intravenous injection of heroin into the femoral vein.
      The patient had not used steroids, did not smoke and did not drink excessively.
      The patient did not present with any systemic diseases that may cause ANFH. ANFH
      often causes changes to the bone mass of the femoral head, particularly, the
      weight-bearing bone region. Imaging examination revealed that in addition to the
      bilateral hip joints, widespread changes to the bone mass existed in the
      peripheral area, where phlebitis and disseminated thrombosis had been caused by
      the injection of heroin. These results suggest that this ANFH case was related to
      the injection of heroin. This case is different from other cases of ANFH which
      have been caused by steroids and other factors, including smoking, alcohol intake
      and cytotoxic agents.

PMID- 24137313
TI  - Percutaneous transluminal radiofrequency closure of the coronary artery in animal
      studies.
AB  - The aim of this study was to investigate the safety and effectiveness of a novel
      method for the selective transcoronary closure of small coronary arteries by the
      intraluminal application of radiofrequency (RF) energy. Twenty-six small
      (diameter of 1-2 mm) coronary artery branches were selected in 13 dogs. An RF
      electrode wire (CRW-Zcy) was placed into the target vessel and a coronary balloon
      was used to transiently block the blood flow and limit damage to the proximal
      vessel. A therapeutic dosage of 20-30 W of RT energy every 10-30 sec (selected
      according the diameter of the target artery) was discharged via the CRW-Zcy
      inside a microcatheter two or three times in order to achieve arterial closure. A
      high dosage of 60 W every 120 sec of RF energy was used to conduct the safety
      study. All 26 branches were successfully closed resulting in the complete
      blockage of the antegrade and retrograde flows. The area of injury was limited to
      the target artery and the supplied myocardium. High-dose RF did not cause injury
      to the adjacent vessels and myocardium. The animals tolerated the procedure well
      without any untoward systemic effects. A follow-up angiography at two weeks
      revealed no evidence of recanalization or retrograde filling of the target
      artery. Percutaneous transluminal radiofrequency closure is a safe and effective
      interventional approach for closing the small coronary arteries, and is
      potentially valuable for further investigation.

PMID- 24137314
TI  - Recombinant expression and downstream processing of the disulfide-rich tumor
      targeting peptide chlorotoxin.
AB  - Chlorotoxin (CTX) is a scorpion-derived disulfide-rich peptide that targets
      malignant tumors by binding the cell surface matrix metalloproteinase-2 and
      annexin A2. Various CTXs labeled with functional moieties have shown great
      potential for tumor diagnosis and treatment. In the present study, we established
      an efficient approach for preparing mature CTX that may be used for experimental
      and therapeutic purposes. The designed CTX precursors carried either a 6xHis-tag
      or a 6xHis-tag and a glutathione transferase (GST)-tag and were recombinantly
      expressed in Escherichia coli. Following S-sulfonation, the precursors were
      purified using immobilized metal-ion affinity chromatography. Subsequent to the
      removal of the tag by enterokinase cleavage and in vitro oxidative refolding,
      mature CTX was obtained with a considerable yield. The yield of mature CTX whose
      precursors carried a 6xHis-tag and a GST-tag (2 mg per liter of culture) was ~10
      fold that of the mature CTX whose precursors carried a 6xHis-tag (150-200 MUg per
      liter of culture). The folded CTX inhibited the migration of glioma cells in a
      concentration-dependent manner, suggesting it was biologically active.

PMID- 24137315
TI  - Inhibition of SENP1 induces radiosensitization in lung cancer cells.
AB  - Lung cancer is one of the most common and lethal types of malignancy. To date,
      radiotherapy and chemotherapy have been used as the two major treatment methods.
      However, radioresistance of lung cancer remains a therapeutic hindrance. The aim
      of this study was to identify whether small ubiquitin-related modifier (SUMO)
      specific protease 1 (SENP1) is a marker of radioresistance that may serve as a
      target for enhancing the efficacy of lung carcinoma radiotherapy. SENP1 was
      observed to be overexpressed in lung cancer tissues, and the modulation of SENP1
      expression was demonstrated to significantly affect the proliferation of lung
      cancer cells. Moreover, silencing the expression of SENP1 using small interfering
      RNA (siRNA) significantly sensitized lung cancer cells to radiation.
      Mechanically, it was demonstrated that SENP1 depletion significantly enhanced
      ionizing radiation (IR)-induced cell cycle arrest, gamma-H2AX expression and
      apoptosis. Thus, these data suggest that SENP1 may be a desirable drug target for
      lung carcinoma radiotherapy.

PMID- 24137316
TI  - Coexistence of non-functional ectopic thyroid tissue and a normal thyroid: A case
      report.
AB  - The aim of this study was to report a rare case of non-functional ectopic thyroid
      tissue in the neck with a coexisting normal thyroid. A 36-year-old female
      presented with a mass in the anterior neck. The thyroid function of the patient
      was normal. Ultrasonography and computed tomography (CT) revealed a normal
      thyroid gland and a solid mass in the middle lower neck. Scintigraphy showed a
      normal thyroid and the mass did show any uptake of 99mTcO4- . The patient
      underwent en bloc resection. During surgery, the mass was observed to be well
      encapsulated and completely separated from the thyroid gland. Histology revealed
      it as ectopic thyroid tissue. The patient had an uneventful recovery.

PMID- 24137317
TI  - Erlotinib: An enhancer of radiation therapy in nasopharyngeal carcinoma.
AB  - The aim of this study was to explore the effects of erlotinib combined with
      radiation on human nasopharyngeal carcinoma (NPC) radiosensitivity using the CNE1
      and CNE2 cell lines. Human NPC cells were treated with erlotinib and/or
      radiation. The effect of erlotinib on the radiosensitivity of the cells was
      detected using a clonogenic cell survival assay. The rate of apoptosis and the
      cell cycle were evaluated using flow cytometry. An NPC xenograft model in NOD
      SCID mice was used to evaluate the efficacy of the combination therapy of
      erlotinib with radiation. Erlotinib enhanced the sensitivity of the CNE1 and CNE2
      cells to radiation, with sensitization enhancement ratios (SERs) of 1.076 and
      1.109, respectively. Erlotinib combined with radiation induced G2/M phase cell
      cycle arrest in the two cell lines. The mouse tumor model demonstrated a
      significant reduction in NPC tumor volume in mice treated with erlotinib in
      combination with radiation when compared with that in mice treated with radiation
      alone. Erlotinib combined with radiation provoked G2-M phase cell cycle arrest,
      thereby enhancing the sensitivity of the NPC cells to radiation.

PMID- 24137318
TI  - Unsuspected paraganglioma of the urinary bladder with intraoperative hypertensive
      crises: A case report.
AB  - Paraganglioma of the urinary bladder is rare, accounting for <0.05% of all
      bladder tumors. Common clinical findings in patients with bladder paraganglioma
      include hematuria and intermittent hypertension during urination, along with
      generalized symptoms due to increased levels of catecholamines. Although
      unsuspected bladder paraganglioma may result in intraoperative hypertensive
      crises, these may be avoided if characteristic imaging signs are observed. The
      present study reports a case in which a patient with unsuspected paraganglioma
      experienced a severe hypertensive episode during cystoscopic tumor resection.
      Although this case had typical computed tomographic characteristics of the
      bladder paraganglioma, the possibility of the paraganglioma pre-operatively was
      not taken into account.

PMID- 24137319
TI  - Effect of Smilax china L.-containing serum on the expression of POLD1 mRNA in
      human hepatocarcinoma SMMC-7721 cells.
AB  - Bock greenbrier rhizome, also known as Smilax china L. rhizome, induces heat
      clearing and detoxification and dispels wind dampness. Additionally, this Chinese
      medicine has been shown to function as an anticancer compound in various types of
      cancer. The aim of the present study was to investigate the mechanism by which
      Smilax china L.-containing serum suppresses SMMC-7721 human hepatocellular
      carcinoma (HCC) cell growth as well as to determine its effect on the expression
      of DNA polymerase delta catalytic subunit gene 1 (POLD1). SMMC-7721 human HCC
      cells were cultured with serum containing various amounts of Smilax china L. for
      24 h. The cells were also cultured in blank serum or serum containing a drug used
      in Western medicine (cyclophosphamide; CTX) as a positive control. HCC cell
      growth and proliferation were determined using the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution and
      apoptosis were analyzed by flow cytometry, and the expression of POLD1 mRNA was
      detected by quantitative polymerase chain reaction (PCR). The number of cells
      following culture with Smilax china L.-containing serum was observed to be
      decreased. There was significant growth inhibition in the Smilax china L.-treated
      cells (shown in the high concentration serum group, volume fraction 30%), which
      was significantly different from the inhibition observed in the control group
      (P<0.05). Among the various cell cycle phases following culture, the percentage
      of cells in the S phase was significantly increased, and the percentage of cells
      in the G0/G1 phase was decreased; these percentages were significantly different
      from the percentages of the control cells (P<0.05). The results obtained
      following quantitative PCR showed a significant reduction in POLD1 expression.
      Smilax china L.-containing serum directly suppressed cell growth and induced the
      apoptosis of human HCC cells. However, the number of cells in the S phase was
      reduced. This mechanism is suggested to be associated with the suppression of
      POLD1 expression.

PMID- 24137320
TI  - Endocrine resistance in breast cancer: Current status and a perspective on the
      roles of miRNAs (Review).
AB  - Current endocrine therapies for females with estrogen receptor-positive breast
      cancer have facilitated substantial improvements in outcomes. The effectiveness
      of endocrine therapy is limited by either initial de novo resistance or acquired
      endocrine resistance. Multiple mechanisms responsible for endocrine resistance
      have been proposed, including deregulation of various components of the estrogen
      receptor (ER) pathway, alterations in cell cycle and cell survival signaling
      molecules, and the activation of escape pathways. Dysregulation of miRNA
      expression has been associated with experimental and clinical endocrine therapy
      resistance. miRNAs are pivotal to understanding the complex biological mechanism
      of endocrine resistance, and may serve as novel candidate predictive and
      prognostic surrogates and therapeutic targets. This review focuses on current
      progress concerning the roles of miRNAs in endocrine resistance, and discusses
      the challenges and opportunities for implementing miRNA-based assays and
      treatment for patients with endocrine-resistant breast cancer.

PMID- 24137321
TI  - A new emergency in oncology: Bone metastases in breast cancer patients (Review).
AB  - Breast cancer (BC) is the most common tumour in females and as a result, the
      management of such patients is a major public health issue. A high percentage of
      BC patients develop bone metastases (BMs), occasionally even several years
      following the initial diagnosis. BMs are responsible for high morbidity and a
      reduced quality of life with the onset of various clinical complications defined
      as skeletal-related events (SREs), including pathological fractures, spinal cord
      compression, hypercalcaemia, bone marrow infiltration and severe bone pain,
      requiring palliative radiotherapy. Such complications reduce functional
      independence and quality of life, decrease survival rates and increase healthcare
      costs. The current treatment for metastatic BC aims to achieve meaningful
      clinical responses, an improved quality of life, long-term remission, prolonged
      survival and in a small percentage of cases, a complete cure. The treatment of
      this malignancy has become progressively complex, including well-known antitumour
      agents or bone-targeted molecules aimed at preventing bone complications and
      improving patient quality of life and the treatment outcome of a
      multidisciplinary programme. The importance of a multi disciplinary approach in
      the management of BMs is also widely accepted. The major complication of BMs are
      SREs which are responsible for reducing prognoses and patient quality of life and
      are correlated with high rates of hospitalisation with the subsequent social and
      economic consequences. For these reasons, it is crucial to prevent where possible
      or to identify and treat SREs promptly in an attempt to mitigate the ever
      increasing clinical and economic burden.

PMID- 24137322
TI  - Oxygen metabolism in oral cancer: HIF and GLUTs (Review).
AB  - Oral cancer is a significant cause of morbidity and mortality, and has a poor
      prognosis. This has encouraged additional studies into factors that may affect
      the development of this disease. The biological behavior of malignant neoplasms
      is complex. Studies have investigated the energy metabolism of tumor cells, in an
      endeavor to elucidate the tumor biology. The identification of molecular
      signatures and mechanisms, in order to understand tumor progression, may
      facilitate the identification of novel predictive and prognostic markers.
      Pathways that influence tumor progression, such as those involving hypoxia
      inducible factor (HIF) and glucose transporter (GLUT) proteins, have been the
      targets of recent studies.

PMID- 24137323
TI  - Epigenetic regulation of the human telomerase reverse transciptase gene: A
      potential therapeutic target for the treatment of leukemia (Review).
AB  - Telomerase activation is a critical step in human carcinogenesis through the
      maintenance of telomeres. Telomerase activity is primarily regulated by the human
      telomerase reverse transcriptase gene (hTERT), thus, an improved understanding of
      the transcriptional control of hTERT may provide potential therapeutic targets
      for the treatment of leukemia and other forms of cancer. Epigenetic modulation, a
      significant regulatory process in cell biology, has recently been shown to be
      involved in the regulation of the hTERT gene. Moreover, several epigenetic
      modifiers, including DNA methyltransferase (DNMT) and histone deacetylase (HDAC)
      inhibitors, are now in pre- and early clinical trials of leukemia as
      monotherapies or in combination with other drugs, and have achieved significant
      clinical success. In the present review, the epigenetic mechanisms associated
      with telomerase activity in leukemia, and the therapeutic potential of an
      antitelomerase strategy that combines epigenetic modifiers with telomerase hTR
      subunit small molecule inhibitors are discussed.

PMID- 24137324
TI  - Effect of in vivo administration of reprogramming factors in the mouse liver.
AB  - Cancer is initiated by the transformation of stem cells or progenitor cells via a
      dedifferentiation process that leads to cancer stem cells; however, the process
      involves the activation of growth-promoting oncogenes and the inactivation of
      growth-constraining tumor suppressor genes. The introduction of defined factors,
      such as those encoded by c-Myc, Sox2, Oct3/4 and Klf4, in normal somatic cells
      results in their dedifferentiation into induced pluripotent stem (iPS) cells. We
      previously reported that these defined factors induced the development of induced
      multipotent cancer (iPC) cells from gastrointestinal cancer cells by reducing
      tumor aggressiveness. Previous studies indicated that although reprogramming may
      be facilitated by p53 inhibition, gain-of-function oncogenic mutations in p53 and
      oncogenic mutations in Kras-stimulated tumorigenic activity, and their roles in
      vivo are imperfectly understood. Hence, in the present study, the effect of
      direct injection of a Sendai virus (SeV) vector encoding four defined factors in
      vivo was studied using various backgrounds of transgenic and knockout mice, and
      was compared with that of direct injection of microRNAs (miRNAs) diluted with
      cationic lipid. The in vivo imaging data revealed transformation hot spots for
      p53 deficiency or conditional activation of mutant Kras, and the sizes were
      concordant with those in immuno-deficient NOD/SCID and uPA-NOG mice, as well as
      larger compared with those in the control mice. Overall, the present data on in
      vivo reprogramming indicated that Kras activation may facilitate the effect of
      cellular reprogramming in normal liver cells, and the effect of Kras activation
      is more apparent than that of tumor suppressor p53 deficiency. The results also
      revealed that immunodeficiency may increase the effect of reprogramming,
      presumably by blocking the immunosurveillance of transformed cells. These
      findings provide a rationale for further studies to develop a therapeutic
      approach involving direct in vivo reprogramming.

PMID- 24137325
TI  - ER-alpha36-mediated gastric cancer cell proliferation via the c-Src pathway.
AB  - Previously, a novel variant of estrogen receptor (ER)-alpha, ER-alpha36, was
      identified and cloned and reported to mainly mediate non-genomic estrogen
      signaling. More recently, we identified that ER-alpha36 is important for the
      invasion and lymph node metastasis of human gastric cancer. In the present study,
      the c-Src signaling pathway was demonstrated to be involved in the non-genomic
      estrogen signaling mediated by ER-alpha36 in SGC7901 gastric cancer cells.
      SGC7901 cells were subjected to the siRNA-mediated knockdown of ER-alpha36
      (PLKO.1-PURO-SP6-ER-alpha36-L) or transfected with an ER-alpha36 upregulated
      expression plasmid (PLJM1-ER-alpha36-H) and treated with 17beta-estradiol
      (E2beta) and PP2, a c-Src protein inhibitor. The expression of ER-alpha36 and c
      src/p-c-Src and cyclin D1 was examined by western blot analysis, and tumor cell
      growth was analyzed by cell proliferation and nude mouse xenograft assays. The ER
      variant, ER-alpha36, was shown to enhance gastric cancer cell proliferation
      through activation of the membrane-initiated c-Src signaling pathways, indicating
      that ER-alpha36 is important for the regulation of proliferation in gastric
      cancer. In addition, ER-alpha36 was shown to directly interact with c-Src by
      immunoprecipitation. The results of the present study indicate that the use of ER
      alpha36 may be a targeted therapeutic approach in gastric cancer.

PMID- 24137326
TI  - Detection of intravenous leiomyomatosis with intracardiac extension by
      ultrasonography: A case report.
AB  - Intravenous leiomyomatosis (IVL) is characterized by histologically benign tumors
      that exhibit aggressive clinical behavior. On rare occasions, the tumors may
      extend into the regional and systemic veins, thus reaching the heart. This may
      subsequently cause intracardiac leiomyomatosis (ICL), which may lead to
      congestive heart failure and occasionally, sudden fatalities. Due to its rarity
      and diffuse symptoms, the misdiagnosis of ICL is common and as a result, the
      condition may be under-reported. The present study reports a 33-year-old female
      who was admitted to Shandong Provincial Hospital Affiliated to Shandong
      University for myomectomy due to a rapidly growing myoma of the uterus. In
      routine pre-operative abdominal ultrasonography, a moderately sized echoic mass
      in the right internal iliac vein was observed, which extended to the common iliac
      vein, the inferior vena cava and the orifice of the right atrium. A presumptive
      diagnosis of ICL was made. The patient underwent a well-prepared one-stage
      thoraco-abdominal surgical procedure and the pathological report confirmed ICL.
      This case illustrates that the early detection of ICL may prevent a potential
      emergency situation and abdominal ultrasonography may be considered a useful tool
      in the diagnosis of ICL.

PMID- 24137327
TI  - Reduced expression of Snail decreases breast cancer cell motility by
      downregulating the expression and inhibiting the activity of RhoA GTPase.
AB  - Several lines of evidence support an important role for Snail, a transcriptional
      factor, in breast cancer. Overexpression of Snail has been associated with breast
      cancer metastasis, although the specific role of Snail in the process remains
      unclear. To address this issue, the expression levels of Snail, RhoA and
      fibronectin, as well as MMP-2, were reduced in the breast tumor cell lines MDA-MB
      231 and MDA-MB-435S, and their biological responses were studied in vitro and in
      vivo. For the first time, it was observed that downregulated Snail expression is
      correlated with a significant inhibition of the expression and activity of RhoA
      GTPase, as well as MMP-2. The present data provide evidence that Snail promotes
      tumor cell motility and angiogenesis which is mainly mediated through the
      regulation of RhoA activity. In conclusion, the present findings demonstrate a
      key regulatory role for Snail in breast tumor growth and progression.

PMID- 24137328
TI  - Melatonin treatment increases the transcription of cell proliferation-related
      genes prior to inducing cell death in C6 glioma cells in vitro.
AB  - A number of studies have suggested that melatonin possesses anticancer
      properties. However, conflicting data exists with regard to the role of melatonin
      in the treatment of cancer. In the present study, the effects of melatonin on the
      transcriptional regulation of three genes associated with cell proliferation
      (Nestin, Bmi-1 and Sox2), and on C6 glioma cell survival and viability, were
      investigated in vitro to evaluate the use of melatonin in cancer therapy.
      Melatonin was shown to increase the mRNA levels of Nestin, Bmi-1 and Sox2 in a
      similar pattern, with the highest mRNA levels noted at a concentration of 3 mM.
      At higher concentrations of melatonin (5 mM), the mRNA levels of Nestin, Bmi-1
      and Sox2 were reduced from their peak levels, and were correlated with changes
      observed in immunofluorescence morphology studies, cell viability and survival
      assays. Immunofluorescence studies of Nestin-stained cells demonstrated that
      treatment with a higher concentration of melatonin (3 and 5 mM) led to the Nestin
      filaments condensing and rearranging around the cell nuclei, and an alteration in
      the cell morphology. C6 cell viability was also significantly decreased at 3 mM
      melatonin, and cell death was observed at 5 and 10 mM melatonin. These results
      suggested that Nestin, Bmi-1 and Sox2 were strongly correlated with the survival
      of C6 cells following treatment with melatonin, and that high therapeutic
      concentrations of melatonin (>5 mM) were required to induce cell death. These
      findings suggested that the implementation of melatonin in the treatment of
      glioma and other types of cancer may be inhibited by conflicting cell growth
      signals in cells. Therefore, adjunct therapy is required to improve the efficacy
      of melatonin in the treatment of cancer.

PMID- 24137329
TI  - Screening for differentially expressed genes between left- and right-sided colon
      carcinoma by microarray analysis.
AB  - Left-sided colon carcinoma (LSCC) and right-sided colon carcinoma (RSCC) differ
      in their genetic susceptibilities to neoplastic transformation. The present study
      identified 11 genes that were differentially expressed in LSCC and RSCC by
      expression profiling with microarray analysis. Compared with RSCC, the human
      genes for L-lactate dehydrogenase B chain (LDHB), cyclin-dependent kinase 4
      inhibitor D (CDKN2D), phosphatidylinositol-4-phosphate-3-kinase C2 domain
      containing subunit alpha (PI3KC2alpha), protocadherin fat 1 (FAT; a human protein
      that closely resembles the Drosophila tumor suppressor, fat) and dual specificity
      protein phosphatase 2 (DUSP2) were upregulated in LSCC. By contrast, genes for
      ubiquitin D (UBD), casein kinase-1 binding protein (CK1BP), synaptotagmin-13
      (SYT1), zinc finger protein 560 (ZNF560), pleckstrin homology domain-containing
      family B member 2 (PLEKHB2) and IgGFc-binding protein (FCGBP) were downregulated
      in LSCC compared with RSCC. A quantitative polymerase chain reaction (qPCR)
      analysis revealed that the mRNA levels of UBD and CK1BP in LSCC were
      significantly lower compared with those in RSCC (P=0.033 and P= 0.005,
      respectively), whereas the mRNA levels of LDHB and CDKN2D in LSCC were
      significantly higher compared with those in RSCC (P=0.008 and P=0.017,
      respectively). Western blot and immunohistochemical analyses demonstrated that
      the expression of CDKN2D in LSCC was significantly higher compared with that in
      RSCC, while the expression of UBD in LSCC was significantly lower compared with
      that in RSCC. The present study provides important insights into the
      understanding of the molecular genetic basis for the different biological
      behaviors observed between LSCC and RSCC. These insights may therefore serve as a
      basis for the identification of novel colon cancer markers and therapeutic
      targets.

PMID- 24137330
TI  - miR-223 functions as a potent tumor suppressor of the Lewis lung carcinoma cell
      line by targeting insulin-like growth factor-1 receptor and cyclin-dependent
      kinase 2.
AB  - microRNAs (miRNAs) have been hypothesized to function as oncogenes or tumor
      suppressors by targeting specific cancer-related genes. Previous studies have
      reported that miR-223 may serve as a tumor suppressor in a number of cancer
      types, however, knowledge of its targets in non-small cell lung cancer (NSCLC)
      remains limited. In the current study, miR-223 was found to inhibit cell
      proliferation in vitro by CCK-8 assay, growth curves and an anchorage-independent
      growth assay in a Lewis lung carcinoma (LLC) cell line. miR-223 transfection in
      the LLC cells was observed to significantly inhibit migration and invasion,
      induce G2/M arrest and decrease the expression levels of Sca-1, a marker of
      murine stem cells. In addition, miR-223 transfection markedly suppressed AKT and
      ERK signaling, as well as insulin-like growth factor-1 receptor (IGF-1R)-mediated
      downstream signaling, pathways that are crucial for cell proliferation and
      invasion in NSCLC cells. Analyses in C57BL/6 mice demonstrated that miR-223
      suppresses tumorigenicity in vivo. Using a luciferase activity assay and western
      blot analysis, IGF-1R and cyclin-dependent kinase 2 (CDK2) were identified as
      direct targets of miR-223. In the present study, novel cancer-related targets of
      miR-223 were identified and verified in a LLC cell line, indicating that miR-223
      functions as a tumor suppressor, which may fine-tune the activity of the IGF-1R
      pathway in lung cancer. Therefore, increasing miR-223 expression may provide a
      novel approach for the treatment of NSCLC.

PMID- 24137331
TI  - Effect of shRNA-mediated inhibition of Nanog gene expression on the behavior of
      human gastric cancer cells.
AB  - The aim of the present study was to employ RNA interference (RNAi) technology to
      construct and select shRNA-Nanog recombinant plasmids for the inhibition of Nanog
      gene expression and transfer these plasmids into the human gastric cancer cell
      line, SGC-7901, as well as to detect the expression of Nanog and the effects on
      the proliferation, migration, invasion, cell cycle and apoptosis of SGC-7901
      cells. The pshRNA-Nanog interference plasmids were constructed and used to
      transfect SGC-7901 cells using lipofectamine. The expression of the Nanog gene
      was detected by fluorescence microscopy, RT-PCR and western blotting, and the
      most markedly inhibited group was identified. The SGC-7901 cells were transfected
      with recombinant shRNA-Nanog plasmids from the most markedly inhibited group
      using lipofectamine and the effect on proliferation was determined by CCK-8
      assay. The migration and invasion of the SGC-7901 cells was determined by
      Transwell assays, while the cell cycle and apoptosis were analyzed by flow
      cytometry. The group with the highest inhibition rate was successfully
      constructed and identified. It was observed that the proliferation, invasion and
      migration capacity of the cells was reduced, that the cell cycle was arrested at
      the S phase and that apoptosis was significantly increased. The Nanog gene in
      gastric cancer cells is closely associated with cell proliferation, the cell
      cycle, apoptosis and migration and invasion abilities. The present study
      establishes the foundations for a novel approach for the genetic treatment of
      gastric cancer.

PMID- 24137332
TI  - Expression and clinical significance of the Trop-2 gene in advanced non-small
      cell lung carcinoma.
AB  - The Trop-2 gene has been examined in various carcinomas and is reported to be
      significantly associated with prognosis. Little is known with regard to Trop-2
      gene expression in advanced non-small cell lung carcinoma (NSCLC). The present
      study investigated the expression of Trop-2 and its association with the
      prognosis of advanced NSCLC. The clinical records of 87 patients with advanced
      NSCLC, consisting of 37 cases of squamous cell carcinoma (SCC) and 50 cases of
      adenocarcinoma (AdC), together with 17 tumor-adjacent normal tissues, were
      retrospectively evaluated. Trop-2 expression was measured using an
      immunohistochemical method and its association with clinicopathological data and
      prognosis was also evaluated. The expression of Trop-2 was significantly higher
      in the cancer tissues compared with the tumor-adjacent normal tissues, and
      significantly higher in SCC compared with AdC (P=0.018). In SCC, the
      overexpression of Trop-2 was only correlated with the histological grade of the
      tumor (P= 0.035) and no correlation was observed with gender, age, lymph node
      metastasis, TNM stage or Eastern Cooperative Oncology Group (ECOG) performance
      status (PS). In AdC, the over-expression of Trop-2 was correlated with the
      histological grade, lymph node metastasis and TNM stage (P= 0.01, 0.024 and
      0.015, respectively), while no correlation with gender, age or ECOG-PS was
      observed. The survival frequency was significantly higher in the Trop-2-negative
      patients compared with the Trop-2-positive patients [17.25 months (95% CI, 14.922
      19.577) vs. 13.274 months (95% CI, 11.507-15.041); P= 0.008]. The survival time
      was significantly longer in the Trop-2-negative AdC patients [17.275 months (95%
      CI, 14.575-19.975) vs. 11.469 months (95% CI, 11.507-15.041); P= 0.002], but not
      in the SCC patients [17.167 months (95% CI, 12.428-21.906) vs. 14.647 months (95%
      CI, 12.062-17.232); P= 0.276]. The multivariate analysis revealed that Trop-2
      expression [hazard ratio (HR) 2.381; P= 0.038], TNM stage (HR, 2.193; P= 0.03)
      and ECOG-PS (HR, 2.696; P= 0.007) were independent predictors for the survival
      outcome of patients with AdC. These results suggest that Trop-2 overexpression is
      closely correlated with an unfavorable prognosis in advanced NSCLC. Trop-2 is an
      independent prognostic marker and a potential new therapeutic target in advanced
      AdC.

PMID- 24137333
TI  - Prognostic significance of p21, p27 and survivin protein expression in patients
      with oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) accounts for >80% of head and neck
      malignancies. p21, p27 and survivin proteins are abnormally expressed in OSCC and
      have been previously reported to correlate with cell proliferation and apoptosis.
      However, the prognostic significance of p21, p27 and survivin remains
      controversial. The aim of the present study was to investigate the association of
      clinical parameters and prognosis with the levels of p21, p27 and survivin
      expression in patients with OSCC. The levels of the three biomarkers were
      evaluated by immunohistochemical staining in specimens from 110 patients with
      OSCC and each section was scored according to the percentage of positive tumor
      cells and staining intensity. Log-rank test and Cox proportional hazards
      regression were performed to assess the correlation between biomarkers and
      clinical events. The association between the immunoexpression of p21, p27 and
      survivin and clinical pathological variables were analyzed by the chi2 test and a
      non-parametric analysis. The expression of p21 in patients with OSCC was found to
      correlate with the expression of p27 and survivin. The results of the current
      study revealed that the five-year survival rate was significantly lower in
      patients with high p21 expression. In addition, the expression of p27 also showed
      a negative correlation with the five-year survival rate of OSCC, but to a lesser
      extent. By contrast, the expression of survivin was not a prognostic factor for
      OSCC. A Kaplan-Meier analysis and Cox proportional hazards model showed that
      lymph node metastasis and p21 expression were independent prognostic factors of
      OSCC.

PMID- 24137334
TI  - Gene expression of bone morphogenic protein 8B in the primary site, peripheral
      blood and bone marrow of patients with gastric cancer.
AB  - The prognosis for individuals that are diagnosed with gastric cancer remains poor
      due to the high frequency of metastatic disease. In response to tumor-derived
      secreted factors, the bone marrow generates a suitable microenvironment for the
      development of metastasis. However, it is largely unknown whether secreted
      factors in bone marrow associated with metastatic disease of patients with
      gastric cancer are present. Secreted factors from the bone marrow of patients
      with metastatic gastric cancer were identified using a DNA microarray analysis
      and the mRNA expression levels were investigated in 355 bone marrow, 295
      peripheral blood and 144 primary site samples using quantitative PCR (qPCR).
      Using DNA microarray analysis, the present study identified bone morphogenetic
      protein 8B (BMP8B) as a secreted signaling molecule in the bone marrow that was
      associated with the metastatic disease of human gastric cancer. The expression
      levels of BMP8B in the bone marrow of 355 gastric cancer patients were increased
      with metastatic disease. A significant correlation was demonstrated between BMP8B
      mRNA expression in the bone marrow and in the peripheral blood. High BMP8B
      expression in the bone marrow was associated with the diffuse type of gastric
      cancer (P=0.009), lymph node metastasis (P=0.009), liver metastasis (P=0.044) and
      peritoneal dissemination (P<0.001). In the primary site, a multivariate analysis
      revealed BMP8B mRNA expression as one of the independent prognostic factors of
      gastric cancer [hazard ratio (HR), 2.066; 95% CI, 1.132-3.772]. This study
      suggests that BMP8B, a previously unknown secreted factor in cancer progression,
      has the potential to be used as a prognostic biomarker. The present study may
      provide insight into a new mechanism that underlies the dissemination of gastric
      cancer cells.

PMID- 24137335
TI  - A potential diagnostic marker for ovarian cancer: Involvement of the histone
      acetyltransferase, human males absent on the first.
AB  - Human males absent on the first (hMOF), a human ortholog of the Drosophila MOF
      protein, is responsible for histone H4 lysine 16 (H4K16) acetylation in human
      cells. The depletion of hMOF leads to a global reduction in histone H4K16
      acetylation in human cells, genomic instability, cell cycle defects, reduced
      transcription of certain genes, defective DNA damage repair and early embryonic
      lethality. Studies have shown that abnormal hMOF gene expression is involved in a
      number of primary cancers. The present study examined the involvement of hMOF
      expression and histone H4K16 acetylation in clinically diagnosed primary ovarian
      cancer tissues. Clinically diagnosed frozen primary ovarian cancer tissues were
      used for polymerase chain reaction (PCR), quantitative PCR (qPCR), western
      blotting and immunohistochemical staining approaches. A PCR analysis of mRNA
      expression in 47 samples revealed a downregulation of hMOF mRNA in 81% of
      patients, whereas only 13% of patients demonstrated upregulation. qPCR was used
      to validate the frequent downregulation of hMOF expression in the primary ovarian
      cancer tissues. As expected, the analysis of hMOF expression in 57 samples
      revealed that hMOF mRNA expression was significantly downregulated (>2-fold
      decrease) in 65% of patients, while a <2-fold reduction of hMOF was observed in
      10.5% of patients. Furthermore, the expression of hMOF-regulated human leukocyte
      antigen (HLA) complex 5, (HCP5), was also found to be downregulated in >87% of
      patients with a decrease in hMOF. hMOF and its regulated gene, HCP5, are
      frequently downregulated in human ovarian cancer, suggesting that hMOF may be
      involved in the pathogenesis of the disease.

PMID- 24137336
TI  - TGFbeta1 and HGF protein secretion by esophageal squamous epithelial cells and
      stromal fibroblasts in oesophageal carcinogenesis.
AB  - Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with a poor
      prognosis. Cancer-associated fibroblasts (CAFs) affect tumorigenesis by creating
      an environment primed for growth and invasion through the secretion of factors,
      including hepatocyte growth factor (HGF) and transforming growth factor beta1
      (TGFbeta1). In the present study, the levels of alpha-smooth muscle actin (alpha
      SMA), TGFbeta1 and HGF were determined immunohistochemically in oesophageal
      precancerous lesions (low- and high-grade intraepithelial neoplasia; LGIEN and
      HGIEN, respectively), carcinoma in situ (CIS) and squamous cell carcinoma (SCC).
      Immunoreactivity was observed in the cytoplasm of oesophageal epithelial cells
      and stromal fibroblasts. Expression levels of alpha-SMA, TGFbeta1 and HGF
      increased significantly in the following order: normal, LGIEN, HGIEN, CIS and
      SCC. In addition, linear correlations between the expression of alpha-SMA,
      TGFbeta1 and HGF and different lesions were observed. Microvessel density (MVD)
      was measured in all specimens and increased gradually in the normal, LGIEN,
      HGIEN, CIS and SCC specimens, successively. A linear correlation between MVD and
      pathological grade was also observed and the MVD in alpha-SMA-, HGF- and TGFbeta1
      positive groups was higher when compared with that of their negative
      counterparts. The results of the present study indicated that the frequent
      overexpression of TGFbeta1 and HGF proteins, secreted by oesophageal epithelium
      and stromal fibroblasts, promoted the progression of oesophageal precancerous
      lesions via the proliferation of epithelial cells and angiogenesis, through the
      upregulation of vascular endothelial growth factor (VEGF) expression.

PMID- 24137337
TI  - Atrial natriuretic peptide modulates the proliferation of human gastric cancer
      cells via KCNQ1 expression.
AB  - Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that
      regulates mammalian blood volume and blood pressure. ANP signaling through NP
      receptor A (NPR-A)/cyclic guanosine 3'5'-monophosphate (cGMP)/ cGMP-dependent
      protein kinase (PKG) activates various downstream effectors involved in cell
      growth, apoptosis, proliferation and inflammation. Evidence has shown the
      critical role of plasma K+ channels in the regulation of tumor cell
      proliferation. However, the role of ANP in the proliferation of gastric cancer
      cells is not clear. In the present study, the expression of NPR-A in the human
      gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS
      cells were investigated using western blotting, immunofluorescence, qPCR and
      patch clamp assays. The K+ current was also analyzed in the effect of ANP on the
      proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS
      cell line. Lower concentrations of ANP promoted the proliferation of the AGS
      cells, although higher concentrations decreased their proliferation. Significant
      increases in the levels of cGMP activity were observed in the AGS cells treated
      with 10-10, 10-9 and 10-8 M ANP compared with the controls, but no significant
      differences were observed in the 10-7 and 10-6 M ANP groups. The patch clamp
      results showed that 10-9 M ANP significantly increased the tetraethylammonium
      (TEA)- and 293B-sensitive K+ current, while 10-6 M ANP significantly decreased
      the TEA- and 293B-sensitive K+ current. The results showed that 10-10 and 10-9 M
      ANP significantly upregulated the expression of potassium voltage-gated channel,
      KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10
      7 and 10-6 M ANP significantly downregulated the expression of KCNQ1. The data
      indicated that lower and higher concentrations of ANP have opposite effects on
      the proliferation of AGS cells through cGMP-dependent or -independent pathways.
      KCNQ1 upregulation and downregulation by lower and higher concentrations of ANP,
      respectively, have separate effects on the promotion and inhibition of
      proliferation.

PMID- 24137338
TI  - Tumor angiogenesis, macrophages and mast cell microdensities in endometrioid
      endometrial carcinoma.
AB  - The present study aimed to observe and compare the values of microvessel density
      (MVD), mast cell microdensity (McMD) and macrophage microdensity (MphMD) in
      intratumoral areas compared with the advancing edges, and to assess any
      correlations between these values and the degree and stage of the neoplasia. The
      cases of 52 patients who were diagnosed with endometrial carcinoma between 2003
      and 2011 were analyzed, the majority of which were in the first stage of the
      disease (44 cases). Double sequential immunohistochemistry and the hot-spot
      counting method were used to assess the MVD (CD105+ MVD), McMD [tryptase+ (Try+)
      McMD] and MphMD (CD68+ MphMD) densities. The chi2 test, paired Student's t-test
      and the Pearson correlation index were used to assess the significance of the
      results. A weak correlation was observed at the advancing edge only, between
      CD105+ MVD and Try+ McMD (P=0.039). No significant differences were identified in
      the analysis of CD105+ MVD, Try+ McMD and CD68+ MphMD, but wide variations in
      their distribution were observed. Depending on the tumor stage, CD105+ MVD
      exhibited an intratumoral, indirect correlation with Try+ McMD for stage IA
      (P=0.026) and II (P=0.013) tumors. CD105+ MVD presented an indirect correlation
      with CD68+ MphMD in stage IB tumors (P=0.016) and at the advancing edge for well
      differentiated tumors (P=0.027). An analysis of the correlation between CD68+
      MphMD and Try+ McMD indicated that the intratumoral levels of CD68+ MphMD were
      directly proportional with the Try+ McMD values in well-differentiated (P=0.005)
      and stage II (P=0.012) tumors, while at the front of the invasion, this
      correlation was indirect (P=0.010) in stage II tumors. In endometrioid
      endometrial carcinoma (EEC), angiogenesis is at its most active at the advancing
      edge of the tumor, where mast cells play a pro-angiogenic role.

PMID- 24137339
TI  - A GWAS-identified susceptibility locus on chromosome 11q13.3 and its putative
      molecular target for prediction of postoperative prognosis of human renal cell
      carcinoma.
AB  - Genome-wide association studies have been used to identify single nucleotide
      polymorphisms (SNPs) associated with renal cell carcinoma (RCC) in European
      individuals. The current study aimed to evaluate the correlation between
      significant SNPs identified in European individuals and the occurrence and
      postoperative prognosis of RCC in Chinese individuals. A total of 400 cases and
      806 controls were involved in the current study. rs4765623, rs7105934, rs7579899
      and rs1867785 were genotyped using qPCR, and the expression of cyclin D1 in renal
      tissue and RCCs was determined via western blotting and immunohistochemistry. The
      correlation between the SNPs/cyclin D1 expression and overall survival was
      evaluated using multivariate Cox regression analyses. Of the four SNPs, only
      rs7105934 was found to significantly correlate with RCC risk in Chinese
      individuals. The rs7105934 GA + AA genotype was correlated with a reduced risk of
      RCC with an odds ratio of 0.64 (95% confidence interval [CI], 0.43-0.96),
      following adjustment for age. This genotype was found to independently predict an
      improved postoperative prognosis in the multivariate analysis, with a hazard
      ratio (HR) of 0.12 (95% CI, 0.02-0.93). Expression of cyclin D1, a putative
      regulated protein of rs7105934, did not vary in adjacent renal tissue and tumors
      when compared with that of various rs7105934 genotypes. However, cyclin D1
      expression in RCCs inversely correlated with advanced tumor stage, and moderate
      to high expression of cyclin D1 in RCCs independently predicted improved
      postoperative prognosis, with an HR of 0.13 (95% CI, 0.02-0.96). Observations of
      the present study indicate that the rs7105934 A allele is associated with reduced
      risk and improved postoperative prognosis of RCC; however, this effect is
      unlikely to be caused by cyclin D1 expression.

PMID- 24137340
TI  - Arterial interventional chemotherapy and IMRT with concurrent chemotherapy for
      nasopharyngeal carcinoma with intracranial involvement.
AB  - The aim of this study was to ensure a high dose of intensity modulated radiation
      therapy (IMRT) was delivered to tumor tissue with a low dose to normal organs.
      Seldinger interventional techniques were used to inject chemotherapy drugs for
      nasopharyngeal carcinoma (NPC). IMRT was conducted 3 weeks after intervention.
      Primary tumor volume was reduced by 42.76% after 2 doses of interventional
      chemotherapy and intracranial tumor volume was reduced by 55.63%. All patients
      presented grade II and above nasopharyngeal mucositis. In the 2 years following
      radiotherapy, overall survival (OS) was 83.3% and progression-free survival (PFS)
      was 75%. In conclusion, T4 NPC patients with intracranial extension received
      induction chemotherapy followed by IMRT and concurrent chemotherapy, which proved
      to be efficacious and well tolerated.

PMID- 24137341
TI  - Blockade of NF-kappaB nuclear translocation results in the inhibition of the
      invasiveness of human gastric cancer cells.
AB  - The aim of the present study was to investigate the effect of the nuclear factor
      kappaB (NF-kappaB) p65 inhibitor, SN50, on the invasiveness and mechanisms of
      SGC7901 human gastric carcinoma cell xenografts in nude mice. Nude mice were
      randomly divided into model control and SN50 treatment groups. On days 5, 10 and
      15 following treatment, the tumor samples were observed and a selection of
      parameters were recorded, including the level of tumor growth inhibition, the
      pathological changes in the tumor specimens, the expression levels of matrix
      metalloproteinase-9 (MMP-9), proliferating cell nuclear antigen (PCNA), tissue
      inhibitor of metalloproteinases type-1 (TIMP-1) and vascular endothelial growth
      factor (VEGF) and the apoptosis indices in the tumor samples. The results
      demonstrated that treating the tumor with SN50 for 5, 10 and 15 days inhibited
      carcinoma growth in comparison with the control group. Hematoxylin and eosin (HE)
      staining indicated that the level of inhibition increased progressively, in
      correlation with apoptosis. The expression of the MMP-9, PCNA and VEGF proteins
      was observed to be downregulated, while that of the TIMP-1 protein was shown to
      be upregulated, using immunohistochemical staining. In conclusion, the NF-kappaB
      p65 inhibitor, SN50, inhibited the invasiveness of the gastric cancer cells by
      downregulating the protein expression of MMP-9, PCNA and VEGF and upregulating
      the protein expression of TIMP-1. It was further suggested that SN50 may be a
      molecular target of anti-invasion therapy for gastric cancer, and that the
      inhibition of the NF-kappaB p65 signaling pathway may be considered as a
      potential strategy for treating gastric cancer.

PMID- 24137342
TI  - Mutational analysis of the GNA11, MMP27, FGD1, TRRAP and GRM3 genes in thyroid
      cancer.
AB  - Frequent somatic mutations in the GNA11, matrix metalloproteinase (MMP)27, FGD1,
      TRRAP and GRM3 genes have been reported in various types of human cancer, but
      whether these genes are mutated in thyroid cancer is not known. In the present
      study, a mutational analysis of these genes was performed in thyroid cancer cell
      lines and thyroid cancer samples. No GNA11 mutations were identified in the
      papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic
      thyroid cancer (ATC) samples. Additionally, no mutations were identified in the
      MMP27 gene, although three synonymous [C351T (N117N), C1089T (S363S) and G1227A
      (G409G)] single nucleotide polymorphisms (SNPs) were observed infrequently in
      ATC. No mutations were detected in the FGD1 gene, but two infrequent synonymous
      [T2091C (T697T) and A2136G (P712P)] SNPs were observed in PTC. Furthermore, no
      mutations were identified in TRRAP and GRM3, although a frequent synonymous SNP
      [G1323A (T441T)] and infrequent non-synonymous SNP [G1424A (G475D)] of GRM3 were
      observed in PTC. No mutation of these genes was observed in 12 cell lines derived
      from various types of thyroid cancer. The present study reports for the first
      time the mutational status of the GNA11, MMP27, FGD1, TRRAP and GRM3 genes in
      thyroid cancer. No mutations were identified in these genes in the various types
      and cell lines of thyroid cancer. Therefore, unlike in other types of cancer,
      mutations in these genes are absent or uncommon in thyroid cancer.

PMID- 24137343
TI  - Hamartoma of the breast in two patients: A case report.
AB  - Breast hamartomas are rare, benign, tumor-like nodules composed of glandular,
      adipose and fibrous tissue. The hamartoma was first described in 1971 as a
      lipofibroadenoma, fibroadenolipoma or adenolipoma, based on the predominant
      component of the breast tissue. Clinical findings resemble fibroadenoma and if
      there is a palpable mass, the patients may receive an immediate diagnosis. Ductal
      hyperplasia, apocrine metaplasia, calcification and adenosis may occur within the
      hamartoma, with rarer instances of lobular or ductal intraepithelial neoplasms.
      Although hamartoma is usually benign, a malignant transformation is possible. An
      excision and histological examination is necessary for the differential diagnosis
      and also for any epithelial lesions of the hamartoma. Simple excision is enough
      for treatment if there is no coincidental epithelial malignant lesion. The
      patients in the present study were treated by simple excision as there were no
      proliferative changes in the lesions. No recurrence or other problems were
      detected in the 18-month follow-up. The current study presents two cases of
      breast hamartoma that were diagnosed as an adenolipoma and a fibroadenolipoma,
      and then describes the macroscopic and microscopic observations of these lesions.

PMID- 24137344
TI  - Sudden visual loss in the untreated eye of a patient with neovascular glaucoma
      following an intravitreal bevacizumab injection: A case report.
AB  - The current study presents the case of a patient with a rare adverse event
      characterized by sudden vision loss in the untreated eye following an
      intravitreal injection of bevacizumab for neovascular glaucoma (NVG). The patient
      was diagnosed with NVG refractory to Ahmed glaucoma valve implantation and a
      vitreous hemorrhage in the right eye, which was treated with 1.25 mg intravitreal
      bevacizumab. Ten days after the bevacizumab injection, the left eye exhibited
      sudden visual loss. The patient's best-corrected visual acuity (BCVA) decreased
      from 80 to 25 letters [Early Treatment Diabetic Retinopathy Study (ETDRS) chart].
      A fundus examination revealed a swollen optic disk with unclear boundaries,
      retinal hemorrhages and thinning retinal vessels. Fundus fluorescein angiography
      (FA) identified hyperfluorescence in the optic disk and an enlarged foveal
      avascular zone. The visual field revealed quadrantal defects that confirmed the
      diagnosis of anterior ischemic optic neuropathy associated with ischemic
      maculopathy. Six months later, following medical treatment, the patient's BCVA
      was increased to 44 letters. However, a clinical examination found neovessels
      with one papilla disk (PD) above the disk. Laser photocoagulation treatment was
      administered immediately. The area of neovessels above the disk was reduced to
      1/4 PD at the last follow-up. In conclusion, although intravitreal anti-vascular
      endothelial growth factor (Bevacizumab) is an effective treatment for neovascular
      ocular diseases, its adverse effects must be taken into consideration for the
      treatment of NVG. Photocoagulation remains an effective treatment for
      proliferative diabetic retinopathy.

PMID- 24137345
TI  - Fluid biopsy for circulating tumor cells in an occult ovarian cancer patient
      exhibiting bilateral supraclavicular lymph node metastases: A case report.
AB  - Metastases to the supraclavicular region usually originate from the head and neck
      or from infraclavicular tumors. Ovarian primaries of supraclavicular metastases
      are extremely rare. The present study reports the case of a 60-year-old patient
      with a bilateral supraclavicular mass that was diagnosed as a poorly
      differentiated squamous cell carcinoma of unknown primary, following a fine
      needle aspiration biopsy (FNAB) and comprehensive clinical investigation. The
      analysis of a peripheral blood sample using the CellSearch system revealed the
      presence of circulating tumor cells (CTCs) that were positive for epithelial cell
      adhesion molecule (EpCAM) and cytokeratin (CK) expression. Since EpCAM is usually
      expressed in adenocarcinoma, an excisional biopsy of the right supraclavicular
      lymph node was performed. The patient was diagnosed with occult ovarian low-grade
      serous carcinoma by immunohistochemistry. To the best of our knowledge, this is
      the first report to demonstrate that CTCs may be detected in the peripheral blood
      of a patient with cancer of unknown primary (CUP) by using the CellSearch system.
      A literature review was performed to analyze the diagnostic procedures of CUP
      metastatic to the cervical lymph nodes and the clinical features of CTCs.

PMID- 24137346
TI  - Quercetin liposomes protect against radiation-induced pulmonary injury in a
      murine model.
AB  - In the present study, the hypothesis that quercetin liposomes are able to
      effectively protect against radiation-induced pulmonary injury in a murine model
      was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were
      randomly divided into three groups: control, radiation therapy plus saline
      (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation,
      lung injury was assessed by measuring oxidative damage and the extent of acute
      pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the
      malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced;
      the total cell counts and inflammatory cell proportions in the bronchoalveolar
      lavage fluid (BALF), plasma tumor necrosis factor (TNF)-alpha and transforming
      growth factor (TGF)-beta1 concentrations and the hydroxyproline (HP) content were
      significantly increased. Quercetin liposome administration significantly reduced
      the MDA content and increased SOD and GSH-PX activities in the lung tissues, and
      reduced the total cell counts and inflammatory cell proportions in the BALF,
      plasma TNF-alpha and TGF-beta1 concentrations and the HP content in the lung
      tissues. A histological examination revealed suppression of the inflammatory
      response and reduced TGF-beta1 expression and fibrosis scores. Radiation-induced
      oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes
      were shown to protect against radiation-induced acute pneumonitis and late
      fibrosis, potentially by reducing oxidative damage.

PMID- 24137347
TI  - Giant primary retroperitoneal teratoma in an adult female patient: A case report.
AB  - The retroperitoneum is an uncommon location for teratoma in adults. The current
      study presents the case of a rare giant primary retroperitoneal teratoma in a 55
      year-old female. The clinical manifestations, diagnosis and surgical treatment
      procedure of this case are retrospectively reviewed. The patient presented with a
      complaint of an abdominal palpable mass and fullness for 1 month. The patient
      suffered a massive hemorrhage during the first exploratory laparotomyand only a
      small section of the tumor was resected. Pathology revealed a mature
      retroperitoneal teratoma. Eleven months after the first surgery, the tumor was
      resected successfully at the second laparotomy. The surgical specimen was a large
      tumor mass measuring 22*18*10 cm in size and weighing 6 kg. At follow-up, the
      patient was in a stable condition. This case study highlights the importance of
      imaging for the development of a pre-operative strategy and performing a safe
      surgical excision in giant retroperitoneal teratoma cases.

PMID- 24137348
TI  - Reduced expression of Rho GDP dissociation inhibitor 2 mRNA is associated with
      lymph node metastasis in gastric carcinoma.
AB  - Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1 and cdc42, are molecules
      that have significant roles in linking cell shape and cell cycle progression in
      cytoskeletal arrangements and mitogenic signaling. Rho GDP dissociation inhibitor
      2 (RhoGDI2) has recently been identified as a metastasis suppressor gene in
      models of bladder cancer. RhoGDI2 has also been identified as a potential
      regulator of tumorigenesis and cancer progression. The present study aimed to
      clarify the significance of RhoGDI2 gene expression in gastric carcinoma and to
      evaluate the outcome of affected patients. A total of 46 pairs of normal mucosa
      and cancer specimens were obtained from patients who had undergone a gastrectomy
      for primary gastric carcinoma and were subjected to semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) for RhoGDI2. The expression of
      RhoGDI2 mRNA was significantly higher in early-stage gastric cancer specimens
      compared with the normal gastric epithelium samples. By contrast, the depth of
      the tumor was negatively correlated with RhoGDI2 mRNA expression. In addition, a
      reduced expression of RhoGDI2 mRNA was associated with venous system invasion and
      lymph node metastasis. RhoGDI2 mRNA was more frequently expressed in
      differentiated adenocarcinoma compared with poorly-differentiated adenocarcinoma.
      Although the statistical significance was not established, RhoGDI2-positive
      patients tended to have a superior oncological outcome compared with RhoGDI2
      negative patients. The reduced expression of RhoGDI2 mRNA in gastric carcinoma is
      associated with venous system invasion and lymph node metastasis.

PMID- 24137349
TI  - MicroRNA-92 regulates cervical tumorigenesis and its expression is upregulated by
      human papillomavirus-16 E6 in cervical cancer cells.
AB  - MicroRNA (miR)-92 is overexpressed in a number of tumors and has been proven to
      negatively regulate a number of tumor suppressor genes, including phosphatase and
      tensin homologue (PTEN). However, its function and molecular mechanism(s) of
      action in squamous cervical carcinoma (SCCs) have not been well described.
      Furthermore, the correlation between miR-92 and human papillomavirus (HPV)-16 E6
      has not been studied. In the present study, miR-92 expression levels were
      quantified using quantitative PCR (qPCR) in cervical cancer tissues, normal
      cervical tissues and cervical cancer cell lines. SiHa cells were transfected with
      either miR-92-mimics, anti-miR-92 or negative controls. C33A cells were stably
      transfected with pEGFP-N1-16E6 and pEGFP-N1-neo plasmids. The levels of PTEN
      protein expression in the transfected SiHa and C33A cells were evaluated using
      western blot analysis. The effects of miR-92 were detected using cell counting
      kit (CCK)-8 and Transwell assays. HPV16 E6 siRNA was used to detect the
      effectiveness of the E6 protein on miR-92 in the SiHa and C33A cells. miR-92 was
      highly-expressed in the human cervical cancer tissues compared with the normal
      tissues. In the HPV16-positive cervical cancer tissues, the expression of miR-92
      was higher compared with the HPV16-negative cervical cancer tissues. HPV16 E6
      upregulated miR-92 expression in the SiHa- and C33A-pEGFP-N1-16E6 cells. The
      upregulation of miR-92 promoted cell growth and invasion in the SiHa cells. PTEN
      protein expression was decreased in the SiHa cells that were transfected with the
      miR-92 mimic. The data indicated that miR-92 may increase the migration and
      invasion of SiHa cells, partially through the downregulation of PTEN protein
      expression. HPV16 E6 was identified to upregulate miR-92 expression.

PMID- 24137350
TI  - Inhibition of cell migration by ouabain in the A549 human lung cancer cell line.
AB  - The Na+/K+-ATPase alpha subunit is highly expressed in malignant cells. Ouabain,
      a cardioactive glycoside, binds to the Na+/K+-ATPase alpha subunit and inhibits
      the activity of Na+/K+-ATPase. In the present study, the effect of ouabain on the
      migration of A549 cells was analyzed using the wound healing and transwell
      chamber migration assays. The impact of ouabain on the expression of E-cadherin,
      N-cadherin, vimentin, matrix metalloprotease (MMP)-2 and MMP-9 was also
      evaluated. Ouabain treatment not only inhibited the epidermal growth factor (EGF)
      enhanced migration of A549 cells, but also inhibited the basal migration of A549
      cells in the absence of EGF. Ouabain decreased the overexpression of N-cadherin
      and vimentin induced by EGF, and decreased the expression of MMP-2 and -9 in the
      presence or absence of EGF. Na+/K+-ATPase is a potent therapeutic target in lung
      cancer and these observations indicated that the Na+/K+-ATPase inhibitor,
      ouabain, retards the invasion of lung cancer cells.

PMID- 24137351
TI  - RECIST 1.1 and serum thyroglobulin measurements in the evaluation of responses to
      sorafenib in patients with radioactive iodine-refractory differentiated thyroid
      carcinoma.
AB  - The present study was designed to investigate the association between response
      evaluation criteria in solid tumors (RECIST) 1.1 and 1.0, and to explore the
      utility of thyroglobulin (Tg) measurements in assessing tumor responses to
      sorafenib in patients with radioactive iodine (RAI)-refractory differentiated
      thyroid carcinoma (DTC). In total, 23 patients with RAI-refractory DTC were
      enrolled. A comparison of RECIST 1.1 and 1.0 was performed in all patients with
      measurable disease. Following the exclusion of patients who were positive for
      anti-Tg antibody, the correlation between RECIST 1.1 and Tg was investigated in
      patients with measurable disease, and the concordance of the change in Tg between
      these patients and the patients with non-measurable disease only was analyzed
      over time. Tumor responses, assessed by RECIST 1.1 and 1.0, were concordant in
      96% of the 23 records. However, the number of target lesions, according to RECIST
      1.1, was significantly lower than when using RECIST 1.0. Progressive disease (PD)
      was identified in one of the five patients who underwent fluorodeoxyglucose
      positron emission tomography (FDG-PET)/computed tomography (CT) scanning. A
      correlation between the Tg levels and the sum of the diameters of the target
      lesions was verified, with the percentage decrease in Tg levels significantly
      greater than that in the radiograph, demonstrating shrinkage. Furthermore, the
      percentage change in Tg levels was consistent between the patients with
      measurable disease and the subjects with non-measurable disease only. In
      conclusion, in patients with RAI-refractory DTC, RECIST 1.1 is highly concordant
      with RECIST 1.0 in the assessment of responses to sorafenib treatment, with the
      advantage of simplified procedures and the complementary use of FDG-PET. Tg
      measurements, in concordance with RECIST 1.1, are valuable in the evaluation of
      tumor responses.

PMID- 24137352
TI  - Osteolytic myxopapillary ependymoma with marked hyaline degeneration in a 72-year
      old male: A case report.
AB  - Myxopapillary ependymomas (MPEs) are uncommon and account for ~15% of all
      ependymomas. The current study presents a case of rare spinal MPE with abnormal
      hyaline degeneration. The patient was a 72-year-old male with a 10-month history
      of lower back pain. Magnetic resonance imaging revealed a mass involving the L4
      and L5 vertebrae with local bone destruction. The tumor was completely resected.
      Histologically, the majority of the tumor exhibited low cellularity. A marked
      change in hyaline was observed in the blood vessels and stroma. In specific
      areas, the tumor showed reticular or tubular patterning embedded in hyaline
      materials. The tumor cells were cuboidal to columnar in shape with strong
      immunostaining for glial fibrillary acidic protein and S-100. A fluorescence in
      situ hybridization analysis for amplification of the epidermal growth factor
      receptor gene was negative. The results of pathological and immunohistochemical
      studies were consistent with the ependymal nature of neoplastic cells.

PMID- 24137353
TI  - TIM-3 expression in human osteosarcoma: Correlation with the expression of
      epithelial-mesenchymal transition-specific biomarkers.
AB  - Signals from the T cell Ig- and mucin-domain-containing molecules (TIMs) have
      been demonstrated to be actively involved in regulating the progression of
      carcinomas. However, the expression and distribution of these molecules in
      osteosarcoma, the most common primary bone malignancy with poor prognosis, have
      not been investigated. In this study, the expression of TIMs was examined in nine
      invasive human osteosarcomas using immunohistochemistry, and the phenotypes were
      detected by dual immunofluorescence staining. Using immunohistochemistry, it was
      observed that only TIM-3, rather than TIM-1 or TIM-4, was expressed in these
      tumor specimens, where it was localized in the cytoplasm and plasma membrane of
      tumor cells. Dual immunofluorescence staining revealed that the expression of TIM
      3 was observed in all cell types investigated, including CD68+ macrophages, CD31+
      endothelial cells, CK-18+ epithelial cells and PCNA+ tumor cells. Notably, in
      sarcoma cells, TIM-3 was co-expressed with certain biomarkers of epithelial
      mesenchymal transition (EMT), including vimentin, Slug, Snail and Smad. These
      combined results suggest that TIM-3 triggers tumor cells to acquire features of
      aggressive EMT and may be involved in the pathogenesis of this malignancy.

PMID- 24137354
TI  - Sonoporation by low-frequency and low-power ultrasound enhances chemotherapeutic
      efficacy in prostate cancer cells in vitro.
AB  - Combination therapy is used to optimize anticancer efficacy and reduce the
      toxicity and side-effects of drugs upon systemic administration. Ultrasound (US)
      combined with micro-bubbles (UM) enhances the intracellular uptake of cytotoxic
      drugs by tumor cells, particularly drug-resistant cells. In the present study,
      low-frequency and low-energy US (US irradiation conditions: frequency, 21 kHz;
      power density, 0.113 W/cm2; exposure time, 2 min at a duty cycle of 70%; and
      valid treatment time, 84 sec) were used in combination with microbubbles (100
      MUl/ml) to deliver mitoxantrone HCl (MIT) to DU145 cells. The results showed that
      UM did not change the cell viability in the short- or long-term. However, UM
      statistically enhanced the therapeutic effects and up to 31.26+/-3.34% of the
      cells exposed to UM were permeabilized compared with 9.74+/-2.55% of cells in the
      control, when using calcein (MW, 622.53) as a fluorogenic marker. Notably, UM
      affected the migration capability of the DU145 cells at 6 h post-treatment. In
      conclusion, the ultrasonic parameters used in the present study enhanced the
      chemotherapeutic effect and reduced the unwanted side-effects of MIT.

PMID- 24137355
TI  - Pituitary protein 7B2 plasma levels in patients with liver disease: Comparisons
      with other hormones and neuropeptides.
AB  - 7B2, a protein initially isolated from the porcine pituitary gland, has been
      identified in numerous animal and human tissues, with the highest concentrations
      in the pituitary and hypothalamus. The 7B2 molecule is highly evolutionarily
      conserved and is considered to be indispensable in the function and regulation of
      proprotein convertase 2 (PC2). In the present study, the plasma 7B2
      immunoreactivity (7B2-IR) of 18 patients with liver disease was studied. Of these
      patients, seven (three male and four female), aged 37-67 [54.6+/-13.5 (SD)]
      years, suffered from liver cirrhosis of cryptogenic (n=2) or alcoholic (n=5)
      aetiology. The remaining 11 patients (four male and seven female), aged 22-76
      [56.1+/-17.6 (SD)] years, suffered from miscellaneous liver abnormalities. The
      clinical diagnosis was confirmed in the majority of patients by the histological
      examination of a percutaneous liver biopsy or by appropriate radiological
      investigations. Plasma bilirubin, alkaline phosphatase, aspartate
      aminotransferase, albumin, prothrombin time, electrolytes, urea and creatinine
      were measured. The plasma 7B2-IR levels were estimated using a sensitive
      radioimmunoassay (RIA), and the elution position of 7B2-IR was verified by gel
      chromatography. The mean plasma 7B2-IR concentration in patients with liver
      disease was 99.44+/-15.9 pmol/l. In the patients with hepatocellular damage due
      to metastatic tumours [Ca bronchus, carcinoid (n=6)], the 7B2-IR concentrations
      were significantly higher [185+/-36.9 pmol/l, (P<0.05)] compared with the overall
      subjects with liver damage. The results of the present study demonstrate that 7B2
      IR is increased in liver disease, with the highest levels detected in patients
      with tumourous liver conditions.

PMID- 24137356
TI  - miR-222 is upregulated in epithelial ovarian cancer and promotes cell
      proliferation by downregulating P27kip1.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of female reproductive
      system cancer mortality in females. The majority of cases of ovarian carcinomas
      are not identified until a late stage. Identifying the molecular changes that
      occur during the development and progression of ovarian cancer is an urgent
      requirement. MicroRNAs (miRNAs) have been identified as gene expression
      regulators that induce mRNA degradation or translation blockade through pairing
      to the 3' untranslated region (3-'UTR) of the target mRNAs. In the present study,
      miR-222 was observed to be frequently upregulated in ovarian cancer. miR-222
      upregulation induced an enhancement of ovarian cancer cell proliferation
      potential, possibly by downregulating its target, P27Kip1. A bioinformatic
      analysis showed that the 3'-UTR of the P27Kip1 mRNA contained a highly-conserved
      putative miR-222 binding site. Luciferase reporter assays demonstrated that
      P27Kip1 was a direct target of miR-222. Consistently, there was an inverse
      correlation between the P27Kip1 and miR-222 expression levels in the ovarian
      cancer cell lines and tissues. Overall, the present results suggest that miR-222
      upregulation in human ovarian cancer may promote ovarian cancer cell
      proliferation during ovarian carcinogenesis.

PMID- 24137357
TI  - Sarcomatoid carcinoma of the renal pelvis: Experience of multiple cases over a
      ten-year period.
AB  - Sarcomatoid carcinoma of the renal pelvis is a rare clinical entity. To the best
      of our knowledge, only 14 cases of this type of neoplasm have been reported in
      the literature to date. In the present study, the records at The First Affiliated
      Hospital, Medicine School of Zhejiang University (Hangzhou, Zhejiang, China)
      between 2000 and 2010 were reviewed to identify patients with primary renal
      pelvis sarcomatoid carcinoma (RPSC). A particular emphasis was placed on the
      treatment, recurrence and survival outcome. Eight patients with RPSC were
      identified and treated with nephrectomy or nephroureterectomy. All of the
      patients presented with Grade 3 RPSC. According to the TNM classification system,
      2 patients were in stage pT2, 5 in stage pT3 and 1 in stage pT4. Adjuvant
      chemotherapy was administered to four patients, and the mean follow-up period was
      27.5+/-41.0 months. In total, 6 patients succumbed to the disease with a mean
      survival time of 7.7+/-5.3 months (range, 1-18 months), while 2 patients were
      free of disease at 54 and 120 months, respectively, following treatment. The mean
      disease-specific survival time was 27.5+/-41.0 months and the 1-year recurrence
      free survival, 1-year survival and overall survival rates were 37.5, 37.5 and
      25%, respectively. The present analysis suggests a poor prognosis for the
      majority of RPSC patients, most likely resulting from the advanced stage of the
      disease at diagnosis and a poor response to systemic therapy. To improve the
      survival rate of RPSC, it is therefore essential to perform an early diagnosis
      and early radical surgery. Intravesical instillation is not essential following
      surgery.

PMID- 24137358
TI  - Matrine effectively inhibits the proliferation of breast cancer cells through a
      mechanism related to the NF-kappaB signaling pathway.
AB  - Matrine is an alkaloid isolated from Sophora flavescens. The present study aimed
      to determine whether matrine effectively inhibits the proliferation of breast
      cancer cells, and the underlying mechanism(s) of its antitumor function. The
      effects of matrine on the cell viability of ER-positive MCF7 cells, HER2-positive
      BT-474 cells and highly metastatic MDA-MB-231 cells were measured using MTT and
      apoptosis assays. Western blot analysis was performed to investigate the
      expression levels of the inhibitor of kappaB (IkappaB) kinase beta (IKKbeta) in
      cells treated with or without matrine. It was observed that the matrine treatment
      resulted in the death of the three types of cancer cells, but significantly less
      toxicity was observed in the control cancer cells. The experimental results also
      suggested that the antitumor effects of matrine on breast cancer cells may be
      associated with the downregulation of IKKbeta expression by matrine, as indicated
      by the western blot analysis results. The present results suggested that matrine
      may be used as an effective drug candidate for treating breast cancers in the
      future, following further research.

PMID- 24137359
TI  - Deleted in liver cancer-1 inhibits cell growth and tumorigenicity in human
      pancreatic cancer.
AB  - Deleted in liver cancer-1 (DLC-1) has been isolated from primary hepatocellular
      carcinoma and demonstrated to be a potential tumor suppressor gene. The aim of
      the present study was to observe the effect of the DLC-1 gene on pancreatic
      cancer cell growth and evaluate the feasibility of using the DLC-1 gene in gene
      therapy for pancreatic cancer. A recombinant plasmid (pcDNA3.1/DLC-1) was
      transfected into PANC-1 cells by liposomes and then the pre-established human
      PANC-1 pancreatic carcinoma cells were injected into athymic nude mice via the
      tail vein. The results showed that the overexpression of DLC-1 in the PANC-1
      cells inhibited cell proliferation in vitro, while the act of introducing DLC-1
      reduced tumorigenicity in the nude mice. The findings suggest that DLC-1 may have
      an effect on the pathogenesis of pancreatic cancer. The DLC-1 gene may be a
      promising target in gene therapy for pancreatic cancer.

PMID- 24137360
TI  - Synergy of Taxol and rhein lysinate associated with the downregulation of ERK
      activation in lung carcinoma cells.
AB  - In previous studies we observed that rhein lysinate (RHL), a salt of rhein and
      lysine that is easily dissolved in water, inhibited the growth of tumor cells in
      breast cancer, ovarian cancer, hepatocellular carcinoma and cervical cancer. The
      present study aimed to investigate the effects of RHL on H460 and A549 non-small
      cell lung cancer (NSCLC) cells using a combination of RHL and Taxol. A 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to
      determine the growth inhibition effect of the drugs in the H460 and A549 cells.
      Cell apoptosis was analyzed by flow cytometry combined with fluorescein
      isothiocyanate-Annexin V/propidium iodide (PI) staining. The expression levels of
      proteins were detected by western blotting. There was a significant reduction in
      the proliferation of the NSCLC cell lines treated with a combination of Taxol and
      RHL. The overall growth inhibition was directly correlated with apoptotic cell
      death. RHL potentiated Taxol-induced cell killing by reducing extracellular
      signal-regulated kinase (ERK) activity and increasing the levels of cleaved
      poly(ADP-ribose) polymerase (PARP) and caspase-3. Notably, the results for the
      Bcl-2 and NF-kappaB proteins also showed downregulation in the combined treatment
      group compared with the single-agent treatment and the untreated control groups.
      The present results showed that RHL potentiates the growth inhibition induced by
      Taxol in NSCLC cells and showed that this synergy may be associated with the
      downregulation of ERK activation.

PMID- 24137361
TI  - Changes in sex hormone levels after radical prostatectomy: Results of a
      longitudinal cohort study.
AB  - The changes in testosterone and gonadotropin levels in patients who have
      undergone radical prostatectomy (RP) for clinically localized prostate cancer
      (PCa) remain unclear. The aim of the present study was to prospectively evaluate
      the changes in serum testosterone (Te), luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) levels in the early months after RP for PCa and the
      correlation between these hormones at various follow-up times. A total of 100
      male patients with clinically localized PCa were consecutively included in the
      study. The serum levels of Te, LH and FSH were measured prior to RP (baseline)
      and at 1 and 3 months post-operatively. Changes in the levels of Te, LH and FSH
      between the baseline and at 1 and 3 months after RP were analyzed with paired
      sample t-tests. The correlations between LH and Te levels at the various follow
      up times were evaluated with a Spearman's rank correlation coefficient. At 1
      month subsequent to RP, the Te levels were significantly decreased (baseline vs.
      1 month, P=0.021) and subsequently recovered to the pre-operative value at 3
      months (baseline vs. 3 months, P=0.372). The mean Te level at baseline was 15.3
      nmol/l, while at 1 and 3 months it was 13.8 and 14.4 nmol/l, respectively. By
      contrast, the levels of LH and FSH were significantly increased at 1 and 3 months
      post-surgery, compared with the baseline value (baseline vs. 1 or 3 months,
      P<0.0001). The pre-operative correlation between LH and Te was lost 1 month after
      RP and recovered after 3 months. Notably, the LH level at 1 month was markedly
      correlated with the Te levels recorded after 3 months. In the present study,
      patients developed compensated hypergonadotropic hypogonadism 3 months after RP.

PMID- 24137362
TI  - CyberKnife therapy of 24 multiple brain metastases from lung cancer: A case
      report.
AB  - Brain metastasis is a significant cause of morbidity and mortality and a critical
      complication of non-central nervous system primary carcinoma. The present study
      describes the clinical case of a 46-year-old male with lung cancer and life
      threatening brain metastases. The patient was diagnosed with lung cancer with a
      clinical stage of T2N0M1 (stage IV). Six months after the initial diagnosis and
      administration of conformal radiotherapy combined with three cycles of
      chemotherapy, an enhanced computed tomography (CT) scan of the brain revealed
      abnormalities with double-dosing of intravenous contrast. The CT scan identified
      >24 lesions scattered in the whole brain. The patient was treated with three
      fraction Cyberknife radiotherapy at 22 Gy, delivered to the brain metastases at
      the Center for Tumor Treatment of People's Liberation Army 107th Hospital.
      Following CyberKnife therapy, a CT scan of the brain revealed that most of the
      tumors had disappeared with almost no residual traces. The stereotactic
      radiosurgery (SRS) conducted using CyberKnife, an image-guided frameless robotic
      technology for whole-body radiosurgery, had produced a marked response. The
      present case report demonstrates that CyberKnife therapy plays a significant role
      in the management of multiple meta-static brain tumors.

PMID- 24137363
TI  - Immune response, clinical outcome and safety of dendritic cell vaccine in
      combination with cytokine-induced killer cell therapy in cancer patients.
AB  - The aim of the present study was to determine the clinical value of autologous
      immunocyte therapy as a standard treatment regimen for patients with cancer. A
      total of 121 patients with cancer were included in this study. Subsequent to
      performing leukapheresis using the Fresenius Kabi System, 1*107 dendritic cells
      (DCs) for the vaccine and 1*109 cytokine-induced killer (CIK) cells for injection
      were prepared. An analysis of the immune phenotypes of HLA2DR, CD80 and CD83 for
      the DCs and of CD3, CD8 and CD56 for the CIK cells, as well as negative detection
      of bacteria and endotoxin, were used as the quality standards. The delayed-type
      hyper-sensitivity (DTH) skin test was used to measure the immune response, while
      physical strength, appetite and sleeping status were analyzed for the clinical
      outcome. Fever, insomnia, anorexia, joint soreness and skin rashes were recorded
      as side-effects. Patients received the DC vaccination once a week for six weeks
      and a CIK cell injection six times within four days. In total, 121 cancer
      patients with primary tumors located in the colorectum (43.0%), lung (15.7%),
      breast (11.6%), kidney (5.8%), stomach (4.1%) and other regions (19.8%) were
      included in the study. A positive cell-mediated cytotoxicity response rate of
      76.9% was detected by the DTH skin tests. Improvements in physical strength,
      appetite and sleeping status were observed in 94.1, 83.9 and 76.3% of cases,
      respectively. None of the serious adverse side-effects that commonly occur during
      chemotherapy and radiotherapy were observed. During therapy, 69 cases developed a
      fever that was resolved with antipyretics, dexamethasone or physical cooling,
      while 28 cases developed insomnia combined with excitement, 19 cases complained
      of anorexia, 11 cases complained of joint soreness, which was alleviated using
      analgesics, and 8 cases developed skin rashes. The combined use of CIK cells with
      a DC-based cancer vaccination strategy may be used to target innate and adaptive
      immune mechanisms and synergistically promote positive clinical outcomes. The
      therapy was safe and no serious adverse side-effects similar to those caused by
      chemotherapy and radiotherapy were observed. The regimen may have a beneficial
      effect in the future treatment of patients with cancer.

PMID- 24137364
TI  - Transformed lymphoplasmacytic lymphoma involving the main carina: A case report.
AB  - A 41-year-old male was admitted to Nagoya City University Hospital subsequent to
      experiencing a cough with bloody sputum for a few days. The patient had a 4-year
      history of lymphoplasmacytic lymphoma (LPL) and had achieved a good partial
      response to anticancer chemotherapy. Chest computed tomography (CT) showed an
      endobronchial tumor of the main carina. A bronchoscopy revealed an exophytic
      tumor at the main carina, and autofluorescence imaging bronchovideoscopy showed
      that the tumor and surrounding area were magenta in color. The biopsy specimens
      demonstrated that the endobronchial tumor was composed of large atypical lymphoid
      cells. The patient was diagnosed with a high-grade transformation of LPL. In
      addition to describing a rare case of transformed LPL involving the main carina,
      the present study also summarizes and discusses endobronchial lymphomas, with a
      brief review of a number of published studies.

PMID- 24137365
TI  - Serum vascular endothelial growth factor-C levels: A possible diagnostic marker
      for lymph node metastasis in patients with primary non-small cell lung cancer.
AB  - Accurate tumor staging is essential for selecting the appropriate treatment
      strategy for lung cancer. Computed tomography (CT), or positron emission
      tomography (PET), is the most commonly used non-invasive staging method of lymph
      node (LN) metastases (LNM), but this method remains unsatisfactory. The present
      study measured vascular endothelial growth factor (VEGF)-C levels in serum, tumor
      tissue and LNs to determine the correlation between serum VEGF-C and LNM, and
      also assessed the usefulness of serum VEGF-C as an additional diagnostic marker
      for identifying LNM. A total of 66 patients with non-small cell lung carcinoma
      (NSCLC) or benign tumors of the lung were included in this study, and circulating
      VEGF-C levels were assessed with enzyme-linked immunosorbent assays. RNA
      fractions extracted from the tumor tissues and LNs were subjected to quantitative
      polymerase chain reaction (qPCR) to assess the mRNA levels of VEGF-C. The VEGF-C
      levels in serum, tumor tissue and LNM were significantly higher compared with the
      control group (P<0.05). The VEGF-C levels of patients with LNM were significantly
      higher compared with those without LNM (P<0.05). The VEGF-C levels in the serum,
      tumor tissue and LNM were significantly correlated (P<0.05). With regard to the
      diagnosis of LNM using VEGF-C levels, the serum levels of VEGF-C reached a
      sensitivity of 65.0% and a specificity of 72.2% when a cutoff value of 655.65
      pg/ml was applied. Serum VEGF-C levels may provide additional information for
      distinguishing between the absence and presence of LNM in patients with lung
      carcinoma. The evaluation of serum VEGF-C is complementary to accurate LN staging
      in NSCLC.

PMID- 24137366
TI  - Inflammatory pseudotumor mimicking primary hepatic malignant tumor with hepatitis
      B virus-related cirrhosis: A case report.
AB  - Inflammatory pseudotumors (IPT) of the liver are fairly uncommon lesions. IPTs
      are difficult to diagnose due to the absence of specific symptoms. The correct
      diagnosis is easily missed, particularly in livers with hepatitis B virus (HBV)
      related cirrhosis. The current study presents the case of a 58-year-old male with
      a ten-year history of HBV infection, who was diagnosed with a primary liver tumor
      by computed tomography (CT) and magnetic resonance imaging (MRI). The alpha
      fetoprotein levels ranged within normal limits. A local resection was performed
      and the histopathological analysis identified IPT of the liver. The patient
      recovered well following surgery.

PMID- 24137367
TI  - Small cell lung cancer with endobronchial growth: A case report.
AB  - The current study presents a rare case of small cell lung cancer (SCLC) with
      endobronchial growth in a 68-year-old male. Chest CT scans revealed an ill
      defined mass in the upper lobe of the right lung, with ipsilateral mediastinial
      lymph node swelling. An endobronchial polypoid tumor in the right B3 bronchus was
      located by bronchoscopic examination. The analysis of a biopsy specimen obtained
      from the tumor resulted in a diagnosis of SCLC. Although extremely rare, this
      case highlights the importance of considering a diagnosis of SCLC in patients
      presenting with a pulmonary tumor adjacent to the bronchus, with an endobronchial
      polypoid lesion.

PMID- 24137368
TI  - Small compound 6-O-angeloylplenolin induces caspase-dependent apoptosis in human
      multiple myeloma cells.
AB  - 6-O-angeloylplenolin (6-OAP) is a sesquiterpene lactone agent that has been
      previously demonstrated to inhibit the growth of multiple myeloma (MM) cells
      through mitotic arrest with accumulated cyclin B1. In the present study, the
      levels of apoptosis were analyzed in dexamethasone-sensitive (MM.1S),
      dexamethasone-resistant (U266) and chemotherapy-sensitive (RPMI 8226) myeloma
      cell lines. Enhanced apoptosis was identified following a 48-h incubation with 6
      OAP (0-10 MUM) that induced a dose-dependent decrease in pro-casp-3 and the
      cleavage of its substrate, anti-poly (ADP-ribose) polymerase (PARP). In addition,
      time-dependent cleavage of PARP was also detected in U266 and MM.1S cells. The
      mechanism of 6-OAP cytotoxicity in all cell lines was associated with the
      induction of apoptosis with the presence of cleaved caspase-3 and PARP. In
      conclusion, 6-OAP-induced apoptosis is caspase-dependent. These observations are
      likely to provide a framework for future studies of 6-OAP therapy in MM.

PMID- 24137369
TI  - Bcl-2 correlates with localization but not outcome in human osteosarcoma.
AB  - bcl-2 is a member of the bcl-2 family that inhibits apoptosis, plays a crucial
      role in cell viability and is expressed in various types of tumors. With respect
      to inconsistent results in previous studies, the aim of the present study was to
      generate a clear hypothesis with regards to the value of bcl-2 expression as a
      predictive or prognostic factor in human osteosarcoma. The expression of bcl-2
      was examined immunohistochemically in 49 patients with high-grade osteosarcoma
      and the results were correlated with localization, histological response to
      chemotherapy, survival and the occurrence of metastases. In patients with
      osteosarcoma, 21/49 cases (43%) were positive for bcl-2 expression and the
      remaining cases were negative. A significantly higher expression of bcl-2 was
      observed in central tumors located in the pelvis (83 vs. 37% positive; P<0.05).
      The bcl-2 expression status revealed no statistically significant correlation
      with response to chemotherapy, with 57% of patients with bcl-2-positive tumors
      showing a good response and 43% showing a poor response. No significant
      difference was observed when comparing survival or occurrence in bcl-2-positive
      and -negative tumors. In conclusion, the results of the present study indicate
      that, despite higher bcl-2 expression in central osteosarcoma, the expression in
      high-grade osteosarcoma is not a reliable prognostic or predictive marker.

PMID- 24137370
TI  - Perforated sarcomatoid carcinoma of the jejunum: Case report.
AB  - Sarcomatoid carcinomas exhibit features that are common to epithelial and
      mesenchymal tumors. These carcinomas are rare, particularly in the small
      intestine. In the current case report, we describe a case of an intestinal
      sarcomatoid carcinoma in a 70-year-old Chinese female. Sarcomatoid carcinoma was
      confirmed based on light microscopy and immunohistochemical observations. The
      patient presented with symptoms of acute abdomen, which was due to an intestinal
      perforation caused by sarcomatoid carcinoma of the small bowel. Patients with
      sarcomatoid carcinoma are usually associated with a poor prognosis. However, this
      patient experienced a relatively favorable prognosis, which may be attributed to
      low positivity for Ki67 in the tumor.

PMID- 24137371
TI  - Primary desmoplastic small round cell tumor of the testis: A case report and
      review of the literature.
AB  - Desmoplastic small round cell tumors (DSRCTs) are extremely rare and mainly
      affect adolescents and young adults. The tumors are usually involved with the
      abdominal area and/or the pelvic peritoneum. Only a small number of cases have
      been reported concerning DSRCTs of the testicular region. The present study
      reports a case of DSRCT of the testis with radical orchectomy and systemic
      chemotherapy, leaving the patient disease-free for 14 months. However, the
      patient died of multiple metastasis 12 months later. Furthermore there is a
      review of the English literature to analyze the incidence, site of origin,
      imaging and pathological characteristics of DSRCT.

PMID- 24137372
TI  - Laparoscopic left pancreatectomy for pancreatic sarcomatoid carcinoma: A case
      report and review of the literature.
AB  - Sarcomatoid carcinoma of the pancreas is extremely rare. The current report
      presents a case of carcinosarcoma of the pancreas in a 48-year-old male. Pre
      operative computed tomography scans revealed a large complex cystic and solid
      mass in the tail of the pancreas; the patient underwent a laparoscopic spleen
      preserving left pancreatectomy. The tumor was shown to be made of cystic and
      solid components, with a grossly grey/ white appearance. A histological
      evaluation of the tumor revealed two elements separated from each other, one
      component was a pancreatic ductal adenocarcinoma and the other component
      exhibited a sarcomatous growth pattern, composed of spindle cells and
      multinucleated giant cells. Immunohistochemically, the epithelial area was
      positive for cytokeratin (CK) and negative for vimentin, while the sarcomatoid
      area was negative for CK and positive for vimentin. These observations confirmed
      a diagnosis of pancreatic carcinosarcoma. Although the patient was treated by
      gemcitabine following surgery, the outcome was extremely poor and the patient
      succumbed to sarcomatoid carcinoma three months after the treatment.

PMID- 24137373
TI  - TIPE2 mRNA overexpression correlates with TNM staging in renal cell carcinoma
      tissues.
AB  - Tumor necrosis factor alpha-induced protein-8 like-2 (TIPE2) is a gene that
      maintains immune homeostasis. The aim of the present study was to determine
      whether TIPE2 is associated with renal cell carcinoma (RCC) progression. The mRNA
      expression levels of TIPE2 and myxoma resistance protein 1 (MX1; a type I
      interferon-inducible gene) were investigated in renal cancer tissues. A total of
      46 patients who fulfilled the RCC criteria of the World Health Organization (WHO;
      revised in 2004) and 39 control patients with renal contusions requiring surgical
      extraction were enrolled. Tumor and normal renal tissues were sampled from all
      subjects through surgery. Total RNA was extracted and the expression of the TIPE2
      and MX1 genes was evaluated by quantitative polymerase chain reaction (qPCR)
      analysis. TIPE2 mRNA expression was significantly upregulated in the RCC patients
      compared with the controls (P=0.001), while MX1 mRNA expression was decreased in
      the RCC patients compared with the controls (P=0.0001). Furthermore, the TIPE2
      mRNA expression levels were positively correlated with TNM staging (r=0.803,
      P=0.001) and showed a negative correlation with the MX1 mRNA expression levels
      (r=-0.763, P=0.001) in the RCC patients. These results indicate that the
      increased expression of the TIPE2 gene is markedly associated with RCC and
      suggests an important role for the TIPE2 gene in the pathogenesis of RCC.

PMID- 24137374
TI  - Colorectal cancer screening with fecal occult blood test: A 22-year cohort study.
AB  - The aim of the present study was to investigate the efficacy of colorectal cancer
      (CRC) screening with a three-tier fecal occult blood test (FOBT) in the Chinese
      population. The study was performed between 1987 and 2008 at the Beijing Military
      General Hospital, in a cohort of army service males and females aged >50 years.
      Between 1987 and 2005, a three-tier screening program, comprising guaiac-based
      FOBTs (gFOBTs), followed by immunochemical FOBTs for positive guaiac test samples
      and then colonoscopy for positive immunochemical test subjects, was performed
      annually. The cohort was followed up until 2008. The cohort included 5,104
      subjects, of which, 3,863 subjects participated in screening (screening group)
      and 1,241 did not (non-screening group). The two groups did not differ in age,
      gender or other major risk factors for colon cancer. Overall, 36 CRCs occurred in
      the screening group and 21 in the non-screening group. Compared with the non
      screening group, the relative risk for the incidence and mortality of CRC was
      0.51 [95% confidence interval (CI), 0.30-0.87] and 0.36 (95% CI, 0.18-0.71),
      respectively, in the screening group. The general sensitivity of this three-tier
      FOBT was 80.6% (95% CI, 65.3-91.1). Thus, annual screening using the three-tier
      FOBT program may reduce the CRC incidence and mortality rate.

PMID- 24137375
TI  - Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis
      in gastric cancer cells.
AB  - Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the
      traditional Chinese medicinal herb Chuanxiong and several studies have shown it
      to possess anticancer properties. However, its effectiveness in gastric cancer
      and its cellular mechanisms are relatively unknown. The present study aimed to
      investigate the effect of TMPZ on SGC7901 cells, and it was demonstrated that a
      high dose of TMPZ inhibited cell viability and induced apoptosis by stimulating
      AMP-activated protein kinase (AMPK) through the generation of reactive oxygen
      species (ROS). Furthermore, TMPZ-induced apoptosis resulted in the sequential
      events beginning with the translocation of Bax, the collapse of mitochondrial
      membrane potential (DeltaPsim), the release of cytochrome c and the activation of
      caspase-9 and -3. Each of these events was inhibited by compound C, a
      pharmacological inhibitor of AMPK. To the best of our knowledge, these results
      demonstrate for the first time that the induction of apoptosis by TMPZ in gastric
      cancer cells is associated with the activation of the ROS/AMPK pathway. AMPK
      activation induces apoptosis through the mitochondrial apoptotic pathway. In
      addition, these results raise the possibility that TMPZ may have a future
      therapeutic role in gastric cancer.

PMID- 24137376
TI  - Complete regression of advanced prostate cancer for ten years: A case report and
      review of the literature.
AB  - Long-term complete regression of prostate cancer (PCa) is a rare phenomenon. The
      current report presents the case of an advanced PCa patient with rare clinical
      features. Following the generation of a definitive diagnosis, the patient was
      administered with flutamide treatment (0.25 g flutamide) 3 times a day, for 5
      consecutive years, prior to surgical castration. Following surgery, 3.75 mg
      enantone was injected (i.h.) once per month for 3 months, without suspending the
      flutamide treatment. In addition, traditional Chinese herbal medicine was
      administrated immediately following surgery. Strontium-89 radiotherapy was
      performed for multiple bone metastases, and the multiple metastatic lesions (lung
      and bone) of the individual disappeared in <7 months. The patient has currently
      survived for >10 years with no development of castration resistance or signs of
      recurrence. Nadir prostate-specific antigen (PSA) levels had remained at <0.1
      ng/ml following the initial treatment, and the erythrocyte sedimentation rate
      (ESR) value was high and had been observed to fluctuate during the treatment. The
      present case report considers the role of the androgen-receptor in PCa and
      indicates that careful interpretation of nadir PSA and ESR levels may aid in the
      prediction of patient prognosis.

PMID- 24137377
TI  - Antimutagenic activity and preventive effect of black tea on buccal mucosa
      cancer.
AB  - A black tea product was evaluated for anti-mutagenic and in vivo anticancer
      effects. At concentrations of 1.25 and 2.5 mg/plate, black tea exhibited anti
      mutagenicity with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the Salmonella
      typhimurium TA100 strain. A Kunming (KM) mouse buccal mucosa cancer model was
      established by injecting mice with U14 squamous cell carcinoma cells. Following
      injection, the wound at the injection site was smeared with black tea. It was
      observed that the tumor volumes for the groups treated with different
      concentrations of black tea were smaller than the control groups. The sections of
      buccal mucosa cancer tissue showed that cancer development in the black tea
      groups was weaker compared with that in the control group. Similar results were
      observed in the lesion section of the cervical lymph. Using reverse transcription
      polymerase chain reaction (RT-PCR), the black tea groups demonstrated an increase
      in Bcl-2-associated X protein (Bax) and a decrease in B cell lymphoma-2 (Bcl-2)
      expression, compared with the control groups. The results demonstrated that black
      tea had an improved antimutagenic effect and in vivo buccal mucosa cancer
      preventive activity compared with the untreated control in mice.

PMID- 24137378
TI  - Nicotinamide-mediated inhibition of SIRT1 deacetylase is associated with the
      viability of cancer cells exposed to antitumor agents and apoptosis.
AB  - Silent mating-type information regulation 2, homolog 1 (SIRT1) represents an NAD+
      dependent deacetylase that regulates the processes of stress response and cell
      survival. However, the functions of SIRT1 in stress- and drug-induced apoptosis
      remain elusive. The present study was designed to determine the effects of SIRT1
      in tumor cells subjected to antitumor agent treatment and to identify the
      underlying mechanisms during the stress response. Several of the most commonly
      used antitumor medications [arsenic trioxide (As2O3), Taxol and doxorubicin
      (doxo)] were selected to treat MCF-7 human breast cancer cells with or without
      nicotinamide (NAM) inhibition. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) was used to test cell viability. SIRT1 expression was
      tested by immunoblot analysis. The typical hallmarks of apoptosis (chromatin
      condensation, apoptotic bodies, sub G1 change and Annexin V+/PI- stained cells)
      were detected by Hoechst 33342 staining, flow cytometry and Annexin V+/PI-
      staining following NAM treatment. The cleavage of poly(ADP-ribose) polymerase
      (PARP) and caspases 9, 6 and 7 was detected through immunoblot analysis.
      Augmented SIRT1 expression was observed only at low concentrations (>80% cell
      viability) and the inhibition of SIRT1 deacetylase by NAM decreased the viability
      of the cancer cells exposed to low concentrations of antitumor agents. NAM
      induced typical apoptosis in the MCF-7 tumor cells, accompanied by the activation
      of the caspase cascade. SIRT1 promotes cellular survival at certain stress levels
      by its deacetylase function. The SIRT1 deacetylase inhibitor, NAM, triggers the
      activation of the caspase cascade and induces typical apoptosis in MCF-7 cells.

PMID- 24137379
TI  - Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the
      third- or fourth-line treatment: A retrospective multicenter experience.
AB  - Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat
      patients with advanced gastrointestinal stromal tumors (GISTs). The present study
      evaluated the efficacy and tolerability of sorafenib therapy for patients with
      GISTs. Between January 2001 and November 2012, 25 patients, from multiple
      centers, who had received sorafenib as the third- or fourth-line treatment for
      GISTs were investigated retrospectively. In total, 17 patients were male and
      eight were female. The median age was 54.0 years (range, 16-82 years). From the
      patients, 21 received imatinib for longer than six months and four received it
      for less than six months. The clinical benefit rate of sorafenib was 40.0%.
      Treatment-related adverse events were reported in 72% of patients. These adverse
      events were generally mild to moderate in intensity. The median progression-free
      survival (PFS) and overall survival (OS) times of the patients who received
      sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage
      was an independent prognostic factor for PFS and OS. Sorafenib is an effective
      treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an
      acceptable tolerability.

PMID- 24137380
TI  - Combining angioplasty with percutaneous microwave ablation for treating primary
      Budd-Chiari syndrome associated with hepatocellular carcinoma in two patients: A
      case report.
AB  - Percutaneous transluminal angioplasty using balloon catheters for Budd-Chiari
      syndrome (BCS) and transcatheter arterial chemoembolization (TACE) for
      unresectable hepatocellular carcinoma (HCC) have become increasingly accepted as
      alternative therapeutic modalities. However, few studies have investigated the
      clinical efficacy of combining percutaneous microwave ablation with angioplasty
      for patients with BCS complicated by HCC. In the present study, a safe and
      effective method for treating BCS associated with HCC is presented. Color Doppler
      ultrasonography, magnetic resonance imaging (MRI), computed tomography (CT),
      inferior venacavography, hepatic arteriogram and cytological examinations were
      used for the diagnosis. A KY2000 microwave system with an emission of 915 MHz was
      also employed for the treatment. Two patients with BCS associated with HCC that
      were administered different adjuvant drug treatments underwent percutaneous
      transluminal angioplasty and percutaneous microwave ablation successfully, with
      no treatment-related complications. Combining angioplasty with percutaneous
      microwave ablation may represent an alternative method for the treatment of BCS
      associated with HCC.

PMID- 24137381
TI  - Roles of mitochondrial transcription factor A and microRNA-590-3p in the
      development of bladder cancer.
AB  - Mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA
      (mtDNA) replication and transcription. microRNAs (miRNAs) act as key factors in
      the regulation of gene expression. However, the roles of TFAM and certain miRNAs
      and their association in cancer development remain unclear. The present study
      reported that the expression of TFAM was significantly increased in bladder
      cancer, while the expression of miRNA-590-3p was downregulated. The luciferase
      assay showed that TFAM was the direct target of miRNA-590-3p. Furthermore, the
      forced overexpression of miRNA-590-3p significantly inhibited the proliferation,
      migration and colony-forming ability of 5637 cells, which was in contrast with
      the results from the forced overexpression of TFAM in the 5637 cells.
      Furthermore, cell proliferation- and migration-related genes, including
      phosphoinositide-3-kinase (PI3K), Akt, matrix metalloproteinase (MMP)-2 and MMP9,
      were significantly downregulated in the miRNA-590-3p-overex-pressing 5637 cells,
      but upregulated in the TFAM-overexpressing cells. In conclusion, the present
      study suggested that TFAM, a direct target of miRNA-590-3p, may play a
      significant role in the tumorigenesis of bladder cancer and thus may be a
      promising target for cancer therapeutics.

PMID- 24137383
TI  - Tertiary cytoreduction in the setting of recurrent ovarian cancer (Review).
AB  - Ovarian cancer is the most lethal gynecological malignancy, with aggressive
      surgical debulking and adjuvant chemotherapy as the main treatment modalities.
      Optimal debulking during the primary surgery is significantly correlated with
      prolonged survival. As surgical techniques and chemotherapeutic agents improve,
      more patients with prolonged survival may face secondary and tertiary
      recurrences. The role of surgical debulking in secondary cytoreduction (SC) is
      not clearly defined and is based on retrospective series. The treatment of
      patients with primary or secondary recurrences generally consists of second-line
      chemotherapy, but may be performed on medically fit patients in certain
      circumstances. A limited number of studies concerning tertiary cytoreduction (TC)
      in cases of secondary recurrences have been published. In these studies,
      conventional prognostic factors for SC, including ascites, an advanced
      International Federation of Gynecology and Obstetrics (FIGO) stage and/or
      peritoneal carcinomatosis, did not apply to TC, but the post-operative residual
      tumor load was significant in determining the prognosis. A limited number of
      patients with completely-resectable tumors may have an opportunity for a maximal
      cytoreduction in these circumstances. TC appears to result in a favorable outcome
      and moderate complication rates. The surgery is an available option for patients
      with recurrence, in whom a complete tumor resection may be achieved.

PMID- 24137382
TI  - miRNA: The nemesis of gastric cancer (Review).
AB  - microRNAs (miRNAs) are a group of small non-coding RNAs that are ~22 (18 to 25)
      nucleotides (nt) long and have been associated with a variety of diseases,
      including cancer. Increasing evidence indicates that miRNAs are essential in the
      development, diagnosis, treatment and prognosis of a variety of tumors. The
      utility of miRNAs as biomarkers for diagnosis and of target molecules for the
      treatment of cancers is increasingly being recognized. With the discovery of
      circulating miRNAs, a non-invasive approach for the diagnosis and treatment of
      cancer has been identified. This review summarizes the role of miRNAs in the
      development of different tumors, as well as a variety of other biological events.
      Moreover, this review focuses on analyzing the function and mechanism of gastric
      cancer-related miRNAs and investigates the importance of circulating miRNAs in
      gastric cancer, as well as their origin. Finally, this review lists a number of
      the problems that must be solved prior to miRNAs being used as reliable non
      invasive tools for the diagnosis, treatment and prognosis of gastric cancer.

PMID- 24137384
TI  - Polymorphisms of GSTP1, ERCC2 and TS-3'UTR are associated with the clinical
      outcome of mFOLFOX6 in colorectal cancer patients.
AB  - The aim of the current study was to examine whether polymorphisms in drug
      metabolism genes have any clinical impact on patients treated with 5-fluorouracil
      (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients
      with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment
      as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two
      DNA-repair genes were assessed in these patients using polymerase chain reaction
      (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or
      invader techniques. These included a 28-bp tandem repeat in the 5'-untranslated
      region (UTR) and 6-bp deletions in the 3'-UTR of thymidylate synthase (TS),
      methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S-transferase
      pi (GSTP1; IIe105Val), GST theta1 (GSTT1; deletion) and GST MU1 (GSTM1; deletion)
      and the two DNA-repair genes, excision repair cross-complementing-1 (ERCC1;
      Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and
      the clinical outcome, including drug response, progression-free survival (PFS),
      overall survival (OS) and the incidence of peripheral neuropathy, were evaluated.
      Patients with the GSTP1-105 A/A genotype had poor responses to mFOLFOX6 treatment
      compared with those with the GSTP1-105 A/G and G/G genotypes (P=0.01). The median
      PFS of patients with the ERCC2-751 A/A genotype tended to be longer than that of
      patients with the ERCC2-751 A/C genotype (P=0.05). Patients with the TS-3'-UTR 
      6/-6 genotype had a significantly longer OS compared with patients with other
      genotypes (P=0.003). A statistically significant association between the
      incidence of peripheral neuropathy higher than grade 2 and the GSTP1-105 (P=0.03)
      and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression
      analyses. Results demonstrated that polymorphisms in GSTP1-105, ERCC2-751 and the
      3'-UTR of TS may be a statistically significant predictors of clinical outcome.
      GSTP1-105 and GSTM1 genotypes may be useful markers of severe peripheral
      neuropathy in MCRC patients treated with 5-FU/oxaliplatin as first-line
      chemotherapy.

PMID- 24137385
TI  - Endometrioid adenocarcinoma with choriocarcinomatous differentiation: A case
      report and review of the literature.
AB  - A choriocarcinomatous component is rarely present in carcinomas of certain sites
      and few cases of choriocarcinomatous differentiation in endometrioid
      adenocarcinoma have been reported. The present study reports a case of
      endometrioid adenocarcinoma of the uterine corpus with choriocarcinomatous
      differentiation, and discusses the clinicopathological features of this rare
      tumor. A 59-year-old post-menopausal female presented with abnormal vaginal
      bleeding. Magnetic resonance imaging demonstrated a relatively well-circumscribed
      tumor in the uterine corpus and a total cystectomy was subsequently performed. A
      histopathological examination revealed two distinct components in the uterine
      corpus tumor. The first component comprised ~80% of the tumor and was composed of
      poorly-differentiated endometrioid adenocarcinoma. The remaining component
      consisted of mononucleated and syncytial giant cells containing rich eosinophilic
      cytoplasm and large pleomorphic nuclei with coarse chromatin. An
      immunohistochemical analysis revealed that these syncytial giant cells were
      positive for beta-human chorionic gonadotropin (hCG). Therefore, a diagnosis of
      endometrioid adenocarcinoma with choriocarcinomatous differentiation was
      confirmed. The clinicopathological features of nine previously reported cases of
      this tumor were analyzed in addition to the present case. The majority of the
      patients were post-menopausal. Endometrial choriocarcinoma may be considered to
      have a highly aggressive clinical course, since nine of the 10 cases displayed
      metastases and four patients succumbed to the disease. The pathogenesis of the
      choriocarcinomatous component is not well understood. However, genetic studies
      have demonstrated that conventional carcinoma and choriocarcinomatous components
      share common genetic alterations. The choriocarcinomatous component represents
      aberrant differentiation of the conventional carcinoma, however, genetic analyses
      of endometrioid adenocarcinoma with choriocarcinomatous differentiation have not
      been performed.

PMID- 24137386
TI  - Identification of high-risk factors as indicators for adjuvant therapy in stage
      II colon cancer patients treated at a single institution.
AB  - Although post-operative adjuvant chemotherapy (ACT) is only recommended for
      patients with stage II colon cancer who are at a high risk of recurrence, the
      definition of high risk remains unclear. The present study aimed to identify the
      risk factors for recurrence, which may also be indicators for adjuvant therapy,
      using a retrospective analysis of clinicopathological data obtained from stage II
      colon cancer patients who had undergone a curative resection. The present study
      also investigated the effects of ACT in patients who displayed the risk factors
      for recurrence. Univariate and multivariate analyses of the data collected from
      377 stage II colon cancer patients, treated at Kurume University Hospital
      (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and
      compare the risk factors for recurrence between the 163 patients who had
      undergone adjuvant therapy and the 214 patients who had not undergone adjuvant
      therapy. The risk factors for recurrence in patients who had not undergone
      adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice
      the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided
      no benefit to patients who presented with neither risk factor, but significantly
      decreased the recurrence rate in patients presenting with one or both risk
      factors. Based on these findings, serum CEA levels of twice the cut-off value and
      pre-operative bowel obstruction were proposed as indicators in the assessment for
      adjuvant chemotherapy following a curative resection for stage II colon cancer.
      These results warrant further clinical study of ACT in patients with one or both
      risk factors.

PMID- 24137387
TI  - Increased intratumoral fluorothymidine uptake levels following multikinase
      inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model.
AB  - An early identification of the tumor response to sorafenib treatment is
      indispensable for selecting optimal personalized treatment strategies. However,
      at present, no reliable predictors are clinically available. 18F-fluorothymidine
      (18F-FLT) positron emission tomography (PET) is used to assess tumor
      proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1)
      activity. Thus, the present study determined whether FLT was able to evaluate the
      early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC;
      A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice
      bearing A498 tumors were assigned to the control and sorafenib-treated groups and
      the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'
      deoxythymidine (3H-FLT) was injected 2 h prior to the sacrifice of the mice on
      days three and seven following the treatment. 3H-FLT autoradiography (ARG) and Ki
      67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In
      the visual assessment, the intratumoral 3H-FLT uptake level diffusely increased
      following the treatment, while no significant changes were observed in Ki-67 IHC.
      The intratumoral 3H-FLT uptake levels significantly increased by 2.7- and 2.6
      fold on days three and seven following the treatment, while the tumor volume and
      Ki-67 index did not significantly change. Thus, an increased FLT uptake level was
      demonstrated following the treatment, which may indicate the suppression of
      thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by
      sorafenib.

PMID- 24137388
TI  - A distinct histopathological variant of a malignant melanoma with perivascular
      pseudorosettes: A case report.
AB  - Although a rare condition, rosette formation in malignant melanoma has been
      previously documented. The present study describes the second documented case of
      malignant melanoma with perivascular pseudorosettes. A 38-year-old male presented
      with a black nodule on his back. Histopathological study revealed diffuse
      proliferation of neoplastic cells in the dermis and subcutis. A section of the
      tumor (~30%) was composed of a conventional malignant melanoma component. The
      remaining area was comprised of medium-sized polygonal cells with slightly
      eosinophilic cytoplasm and small-to-medium, round nuclei. Melanin pigment was
      rarely observed. A noteworthy observation was the presence of perivascular
      pseudorosette formations, which were characterized by their radial arrangement
      around the blood vessels, with a perivascular, anuclear zone.
      Immunohistochemically, the neoplastic cells were diffusely positive for S-100
      protein and Melan-A and focally positive for HMB-45. Clinicopathological analyses
      of cases of malignant melanoma with rosette formations revealed that the types of
      rosette included the Homer-Wright type (two cases), perivascular pseudorosettes
      (two cases) and an unclassifiable type (one case). Immunohistochemical analysis
      is a useful method for forming a diagnosis as Melan-A or HMB-45 are generally
      expressed in all cases. Rosette formation in malignant melanoma is a distinct
      histopathological variant and may be an under-recognized phenomenon. Therefore,
      its recognition is significant for obtaining an accurate diagnosis of malignant
      melanoma.

PMID- 24137389
TI  - Primary intrahepatic malignant mesothelioma with multiple lymphadenopathies due
      to non-tuberculous mycobacteria: A case report and review of the literature.
AB  - Primary intrahepatic malignant mesothelioma (PIHMM) is an extremely rare tumor
      with clinicopathological characteristics that remain to be elucidated. The
      current study presents the case of a 68-year-old female with PIHMM and multiple
      lymphadenopathies due to non-tuberculous mycobacteria. The patient presented with
      an intrahepatic tumor, 70 mm in diameter, in the right lobe of the liver. An
      ultrasound-guided fine-needle aspiration biopsy of the liver tumor revealed
      findings that were consistent with an intrahepatic malignant mesothelioma. The
      systemic lymph node swellings were due to epithelioid granulomas that were caused
      by non-tuberculous mycobacteria. However, a hepatic rupture occurred due to the
      rapid growth of the liver tumor and consequently, a surgical resection was not
      performed. A review of the literature revealed that the clinicopathological
      characteristics of PIHMM are similar to those of non-occupational mesothelioma.
      However, PIHMM is usually a solitary tumor and is rarely associated with cavity
      effusion in contrast with conventional mesothelioma. Therefore, surgical
      resection with curative intent is often recommended for patients with PIHMM.

PMID- 24137390
TI  - Differential expression of filamin A and its clinical significance in breast
      cancer.
AB  - Changes in filamin A (FLNa) expression contribute to the development and
      progression of numerous malignancies. However, in vitro studies of breast cancer
      have shown conflicting results. Thus, the present study aimed to detect the
      expression of FLNa in breast cancer tissue samples and the association with
      clinicopathological data, in order to provide insightful ex vivo data. A total of
      96 breast cancer and distant normal breast tissues and 20 benign tumor tissue
      specimens were subjected to immunohistochemistry or reverse transcription
      polymerase chain reaction (RT-PCR) analysis of FLNa expression.
      Clinicopathological data were collected to analyze the association with FLNa
      expression. The FLNa protein was overexpressed in breast cancer tissues compared
      with distant normal mammary gland and benign breast tissues. The FLNa protein was
      expressed in 63.5% of breast cancer, with positive rates of 36, 66.7 and 84.6%,
      respectively, in stage I, II and III breast cancer patients (P<0.05).
      Overexpression of the FLNa protein was associated with advanced stage, lymph node
      metastasis, vascular or neural invasion, menstruation state and other risk
      stratifications for breast cancer. The overexpression of FLNa in breast cancer
      was validated by RT-PCR, indicating transcriptional regulation of FLNa
      overexpression in breast cancer. FLNa mRNA and protein were overexpressed in
      breast cancer tissues, which was associated with advanced stage, lymph node
      metastasis and vascular or neural invasion of breast cancer, suggesting that FLNa
      contributes to breast cancer development and progression.

PMID- 24137391
TI  - Antitumor effects of 32P-chromic-poly (L-lactide) brachytherapy in nude mice with
      human prostate cancer.
AB  - The aim of the present study was to investigate the antitumor effects and tissue
      distribution of 32P-chromic-poly (L-lactide) (32P-CP-PLLA) in nude mice with
      human prostate cancer. Tumor models were obtained by transplantation of PC-3M
      tumor cells into male BALB/c nude mice. Animals were randomly divided into
      control, 32P-chromic phosphate (32P-CP) colloid and 32P-CP-PLLA groups (all
      n=20). A series of indices were investigated, including apoptosis of tumor cells,
      rate of apoptosis, expression of caspase 3 and 8, biodistribution and
      intratumoral concentration of 32P-CP-PLLA, intensity of radioactivity, tumor
      volume and microvessel density (MVD). Highly concentrated radioactivity of 32P-CP
      PLLA in the tumor mass was detected by single photon emission computed tomography
      (SPECT) scanning. The residual activities of the 32P-CP-PLLA and 32P-CP colloid
      groups were 3.02+/-0.32 and 1.76+/-0.31 MBq, respectively, on day 14 following
      treatment. The tumor inhibition rates were 67.24+/-3.55 and 55.92+/-7.65%,
      respectively (P<0.01). Necrotic changes, in conjunction with apoptosis, were
      observed in the treatment group. MVD values for the 32P-CP-PLLA and 32P-CP
      colloid groups were 28.24+/-10.07 and 36.15+/-11.06, respectively. 32P-CP-PLLA
      showed an excellent capacity for killing tumor cells, inducing apoptosis and
      inhibiting angiogenesis.

PMID- 24137392
TI  - -216G/T (rs712829), a functional variant of the EGFR promoter, is associated with
      the pleural metastasis of lung adenocarcinoma.
AB  - Numerous mutations and variants in the epidermal growth factor receptor (EGFR)
      gene have been demonstrated to be associated with the occurrence, metastasis and
      prognosis of various types of tumors, including lung cancer. Thus, the present
      study aimed to investigate whether -216G/T (rs712829), a functional polymorphism
      of the EGFR promoter that is able to induce EGFR activation and overexpression,
      is associated with the pleural metastasis of lung adenocarcinoma. The study
      subjects were comprised of 326 patients with primary lung adenocarcinoma and 312
      matched cases with pleural metastasis. The -216G/T genotypes were determined in
      all subjects by PCR amplification and direct DNA sequencing, and EGFR expression
      was also evaluated by immunohistochemical staining in the primary tumor tissues
      with various -216G/T genotype backgrounds. The results showed that the
      frequencies of allele T and genotypes G/T and T/T in the pleural metastasis group
      were significantly higher compared with those in the non-metastasis group, with
      adjusted ORs of 1.46 (95% CI, 1.015-1.963) for G/T and 1.97 (95% CI, 1.051-3.152)
      for T/T. Furthermore, the expression of the EGFR protein was higher in the
      primary lung adenocarcinoma tissues with -216T/T and -216G/T compared with those
      with -216G/G (P<0.05). These results collectively indicate that the -216G/T
      polymorphism in the EGFR promoter is associated with the risk of the pleural
      metastasis of lung adenocarcinoma and that this effect may be associated with 
      216G/T-induced overexpression of the EGFR protein.

PMID- 24137393
TI  - Effects of matrine on the proliferation of HT29 human colon cancer cells and its
      antitumor mechanism.
AB  - Matrine is one of the main active components that is extracted from the dry roots
      of Sophora flavescens. The compound has potent antitumor activity in various
      cancer cell lines. However, the anticancer activity of matrine in colon cancer
      cells remains unclear. The purpose of the present study was to investigate the
      effects of matrine on the growth of human colon cancer cells and the expression
      of the associated proteins. Cancer cell proliferation was measured by 3-(4,5
      dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The cell cycle
      distribution and apoptosis were analyzed by flow cytometry (FCM). The activation
      of the caspases and the expression of pro-apoptotic and anti-apoptotic factors
      were examined using western blot analysis. Matrine was shown to significantly
      inhibit the proliferation of HT29 cells in a dose- and time-dependent manner, and
      also to reduce the percentage of cells in the G2/M phase, which was most
      frequently associated with an increase of cells arrested in the G0/G1 phase of
      the cell cycle. Western blot analysis revealed that matrine induced the
      activation of caspase-3 and -9 and the release of cytochrome C (Cyto C) from the
      mitochondria to the cytosol. Furthermore, the pro-apoptotic factor, Bax, was
      upregulated and the anti-apoptotic factor, Bcl-2, was downregulated, eventually
      leading to a reduction in the ratio of Bcl-2/Bax proteins. The results
      demonstrated that matrine inhibits proliferation and induces apoptosis of HT29
      human cells in vitro. The induction of apoptosis appears to occur through the
      upregulation of Bax, the downregulation of Bcl-2, the release of Cyto C from the
      mitochondria to the cytosol and the activation of caspase-3 and caspase-9, which
      subsequently trigger major apoptotic cascades. Matrine has potent antitumor
      activity in HT29 cells and may be used as a novel effective reagent in the
      treatment of colon cancer.

PMID- 24137394
TI  - Lung cancer and peritoneal carcinomatosis.
AB  - Lung cancer is currently one of the most common malignancies in the world and
      peritoneal involvement is rare in these types of tumors. Clinical manifestations
      of these metastases are also uncommon and include intestinal perforation and
      obstruction. The present study reviewed certain aspects of the complication of
      peritoneal involvement and illustrated it with four cases of patients that were
      diagnosed with primary lung carcinoma and secondary peritoneal carcinomatosis
      (PC). The outcome of these patients is poor and they rarely respond to
      chemotherapy. Surgery is successful in the majority of cases.

PMID- 24137395
TI  - A multiple cavity malignancy involving the renal capsule, pleura and meninges: A
      case report and review of the literature.
AB  - Malignant renal subcapsular effusions commonly arise from primary or metastatic
      renal neoplasms. The current case report presents a rare case of malignancy with
      a massive renal subcapsular effusion accompanied by a malignant pleural effusion
      of an unknown primary site, which underwent progression to carcinomatous
      meningitis during chemotherapy. The type of adenocarcinoma present was determined
      by effusion cytology. Intravenous chemotherapy (docetaxel plus oxaliplatin and
      gemcitabine plus cisplatin) were administered; however, the disease still
      progressed. Time to progression was 9 months during treatment of gefitinib.
      Comprehensive therapies, including intracavity chemotherapy, immunotherapy and
      gefitinib, were shown to be effective and prolonged the patient's survival time.

PMID- 24137396
TI  - Clinical application of iodine-eluting stent in patients with advanced esophageal
      cancer.
AB  - The aim of the present study was to compare the clinical effectiveness of an
      iodine-eluting stent with a conventional stent in patients with advanced
      esophageal cancer. Patients with malignant esophageal cancer were randomly
      assigned to receive a conventional stent (group A) or an iodine-eluting stent
      (group B). Following implantation, the relief from dysphagia, survival time,
      routine blood tests, thyroid function examination and complications were compared
      in the two groups. Groups A and B consisted of 36 and 31 patients, respectively.
      The mean value that the dysphagia score decreased by was significantly lower in
      group A (0.83) compared with group B (1.65). The median survival time was longer
      in group B compared with group A (P=0.0022). No significant differences were
      observed in the severe complications between the two groups (P=0.084). The iodine
      eluting esophageal stent is a relatively safe, feasible and effective treatment
      for malignant esophageal strictures.

PMID- 24137397
TI  - Keap1 mutations in lung cancer patients.
AB  - Kelch-like ECH-associated protein 1 (Keap1) inhibits nuclear factor erythroid 2
      related 2 (NEF2L2; also named NRF2)-induced cytoprotection and has been
      hypothesized to represent a candidate tumor suppressor. We have previously
      reported the somatic mutations of the NRF2 gene (NFE2L2), however, the
      correlation between the Keap1 mutation and the clinicopathological features of
      lung cancer has not been well investigated. Therefore, in the present study, the
      Keap1 mutational status in non-small cell lung cancer (NSCLC) patients was
      investigated by reverse transcription PCR and direct sequencing. The study
      included 76 surgically-removed lung cancer cases from patients of the Nagoya City
      University Hospital in which the EGFR and NFE2L2 mutation status was already
      established. Keap1 mutations were identified in 2 (2.6%) adenocarcinoma patients
      with a history of heavy smoking. These mutations were identified to exist
      exclusively. The Keap1 mutation was only detected in patients with advanced
      adenocarcinoma (4.3%) and the completely exclusive status of this mutation and
      others, including EGFR, Kas, erbB2 and NRF2L2, is likely to improve the selection
      of personalized therapy for lung cancer.

PMID- 24137398
TI  - Esophageal cancer presenting as a brain metastasis: A case report.
AB  - Carcinoma of unknown primary origin (CUP) is defined as the histological
      diagnosis of metastasis without the detection of a primary tumor. The incidence
      of CUP in all patients with a malignant disease has been reported to be between 3
      and 15%. Esophageal cancer is the third most common type of cancer of the
      digestive tract and the seventh most common cause of cancer-related mortality
      worldwide. The overall incidence of the disease is highest in males >50 years
      old. Brain metastases have been reported in only 1.7-3.6% of all patients with
      different types of esophageal cancer. Brain metastasis as the presenting form of
      esophageal carcinoma is highly uncommon. The present study reports the case of a
      patient with an unknown primary tumor who presented with a cerebral metastasis,
      without extra-neurological symptoms. The CUP was subsequently diagnosed as an
      esophageal carcinoma.

PMID- 24137399
TI  - A novel BRCA1 mutation in a patient with breast and ovarian cancer: A case
      report.
AB  - Germline mutations in the human breast cancer genes BRCA1 and BRCA2 account for a
      substantial proportion of familial, early-onset breast and ovarian cancers. The
      present study reports a novel disease-causing BRCA1 mutation, nucleotide
      3020insCT/c.2901insCT, in a 55-year-old Spanish female with breast and ovarian
      cancer. This frameshift mutation creates a premature stop codon at amino acid
      1000, leading to a truncated BRCA1 protein. To the best of our knowledge, this
      mutation has not been previously described in the Breast Cancer Information Core
      (BIC) database or the published literature.

PMID- 24137400
TI  - Metaplastic carcinoma of the breast with transformation from adenosquamous
      carcinoma to osteosarcomatoid and spindle cell morphology.
AB  - Metaplastic carcinoma of the breast refers to a heterogenous group of mammary
      carcinomas that contain a mixture of various cell types, including squamous
      cells, spindle cells and/or a mesenchymal component, such as bone or cartilage.
      To the best of our knowledge, the clinical course of a tumour that has undergone
      a transformation from one type of metaplastic carcinoma to another subtype has
      not previously been reported. The present study reports the five-year clinical
      and pathological course of a metaplastic breast carcinoma in a 55-year-old
      female, who was diagnosed with a sclerosing fibroadenomatous nodule with osseous
      metaplasia and focal atypia. A recurrent tumour was documented four years later,
      showing a predominant component of osteosarcoma with adenosquamous carcinoma.
      Upon pathological review of the initial mass, the diagnosis was changed to low
      grade adenosquamous carcinoma. The patient was treated with breast conserving
      therapy. However, one year later, a recurrent metaplastic carcinoma with spindle
      cell morphology was documented and surgically removed by mastectomy.
      Subsequently, pulmonary invasion of the chest wall occurred and the patient
      eventually succumbed due to the invasive nature of the disease.

PMID- 24137401
TI  - Cyclooxygenase-2 expression in the tumor environment is associated with poor
      prognosis in colorectal cancer patients.
AB  - The development of colorectal cancer (CRC) is commonly accompanied by the
      overexpression of the cyclooxygenase-2 (COX-2) gene, with high levels being most
      common in early colorectal lesions. In the present study, we hypothesized that
      the expression of COX-2 in normal mucosa affects the expression of COX-2 in
      adjacent tumors. COX-2 protein expression levels were determined in tumor tissues
      and the adjacent normal mucosa of 49 paired clinical CRC specimens using western
      blotting and immunohistochemistry (IHC) staining. The majority of specimens
      exhibited an extremely low level of COX-2 expression in the tumor tissue and a
      markedly higher expression level in the adjacent normal tissue, however, high COX
      2 expression in the tumor was shown to correlate with a high recurrence rate and
      poor overall survival. Of the nine CRC cell lines, HT29 showed consistently
      higher levels of COX-2 expression. Therefore, COX-2 expression in the normal
      tissue adjacent to the tumor may be involved in the tumorigenesis of CRC. These
      observations are likely to be useful in determining the significance of COX-2
      expression in the tumorigenesis of CRC.

PMID- 24137402
TI  - Insulin-like growth factor-II mRNA-binding protein 3 predicts a poor prognosis
      for colorectal adenocarcinoma.
AB  - Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) has been recently
      identified as a marker of aggressive behavior in several types of tumors. The aim
      of the present study was to detect the expression of the IMP3 protein in
      colorectal adenocarcinoma (CRA) and to identify a correlation with the
      clinicopathological features of the disease. IMP3 was evaluated in 186 samples of
      CRA using immunohistochemical methods. The correlation between IMP3 expression
      and the clinicopathological features of colorectal cancer was evaluated by the
      chi2 and Fisher's exact tests. Survival rates were calculated using the Kaplan
      Meier method and the correlation between IMP3 protein expression and the
      prognosis of patients with CRA was analyzed using Cox analysis. Of the 186
      adjacent normal mucosa (ANM) cases, the 22 that exhibited dysplasia demonstrated
      weak IMP3 expression and the 164 without dysplasia showed no expression. Of the
      186 CRA cases, immunohistochemical staining for IMP3 was observed in 143 cases
      (76.9%). A comparison of IMP3 expression between the CRA and ANM samples revealed
      stronger immunohistochemical reactivity in the CRA tissues (P<0.01). High IMP3
      expression was associated with differentiation, lymphoid metastasis, TNM stage,
      Ki-67 labeling index and a poor patient outcome (P<0.05). In the multivariate
      analysis, IMP3 emerged as an independent predictor of survival. The present study
      demonstrated that IMP3 is able to promote the aggressiveness of cancer behavior,
      resulting in a poor prognosis for patients with CRA. Consequently, IMP3 may be
      regarded as a novel proliferation and prognostic indicator for patients with CRA.

PMID- 24137403
TI  - Primary osteosarcoma of the breast with abundant chondroid matrix and fibroblasts
      has a good prognosis: A case report and review of the literature.
AB  - The present study describes the case of a 77-year-old female with a recently self
      detected, painless, 7-cm lump in the left breast, without evidence of metastasis
      clinically, who underwent mastectomy with dissection of the axillary lymph nodes.
      The tumor did not invade the chest wall and skin. The tumor was comprised of
      abundant chondroid matrix and fibrous tissue, with focal osteoid matrix, and was
      classified as a chondroblastic/fibroblastic variant. The tumor had a reverse
      zonal pattern. The tumor cells in the central portion were mainly spindle-like
      and sparse with minimal cytological atypia, while the remaining tumor cells in
      the periphery were mainly epithelioid, atypical and dense. Neoplastic osteoid
      woven bone or trabeculae were observed in the central portion of the tumor. No
      metastasis was identified in the axillary lymph nodes. The patient was alive
      without evidence of local recurrence or hematogenous spread at the 60-month
      follow-up.

PMID- 24137404
TI  - Inhibition of hepatocellular carcinoma growth by adenovirus-mediated expression
      of human telomerase reverse transcriptase COOH-27 terminal polypeptide in mice.
AB  - A 27-kDa C-terminal fragment of human telomerase reverse transcriptase, hTERTC27,
      has previously been reported to inhibit the growth and tumorigenicity of HeLa
      human cervical cancer cells and U87-MG human glioblastoma multiforme cells.
      However, the antitumor effects of hTERTC27 in hepatoma and its underlying
      mechanisms are unclear. In the current study, the therapeutic effect of hTERTC27,
      mediated by recombinant adenovirus, in hepatocellular carcinoma (HCC) was
      explored in vitro and in vivo to investigate the possible mechanisms. The results
      indicated that recombinant adenovirus carrying hTERTC27 (rAdv-hTERTC27)
      effectively inhibited the growth and induced apoptosis of the Hepa 1-6 HCC cells.
      Dendritic cells transduced with rAdv-hTERTC27 were highly effective at inducing
      antigen-specific T cell proliferation and increasing the activated cytotoxicity
      of T cells against Hepa 1-6 cells. HCC was inhibited significantly when a single
      dose of 5*107 pfu rAdv-hTERTC27 was administered intravenously. In summary, the
      results of this study demonstrated that rAdv-hTERTC27 may serve as a reagent for
      intravenous administration when combined with telomerase-based gene therapy and
      immunotherapy for cancer.

PMID- 24137405
TI  - Three cases of a peripheral primitive neuroectodermal tumor diagnosed using
      computed tomography or magnetic resonance imaging.
AB  - The present study describes the findings from three cases of peripheral primitive
      neuroectodermal tumors (PNETs) diagnosed using computed tomography (CT) or
      magnetic resonance imaging (MRI). The patients were all diagnosed with PNETs of
      the peripheral central nervous system. All the lesions were soft-tissue masses
      with cystic degeneration. The CT images revealed that the lesions were large and
      inhomogeneous, with unclear borders and cystic degeneration. The surrounding
      tissues and structures were compressed against each other. Following the
      enhancement of the CT, the solid components of the tumors were enhanced, whereas
      the cystic components did not show enhancement. Following the enhanced MRI,
      irregular enhancement was noted in the solid components and the cystic and solid
      masses showed unclear borders. The surrounding tissues were compressed. The solid
      components of the tumors were enhanced, whereas the cystic components showed no
      enhancement. Based on these observations, PNETs were diagnosed. Thus, a CT or MRI
      is mandatory for the precise diagnosis of a peripheral PNET.

PMID- 24137406
TI  - RNA interference-mediated targeting of DKK1 gene expression in Ishikawa
      endometrial carcinoma cells causes increased tumor cell invasion and migration.
AB  - The Wnt signaling pathway plays an essential role in tumor invasion and
      migration. DKK1 functions as an important inhibitor of the pathway and represents
      a promising target for cancer therapy. The aim of the present study was to
      determine the role of DKK1 in endometrial carcinoma (EC) cell invasion and
      migration using RNA interference (RNAi) technology. Ishikawa EC cells were
      transfected at high efficiency with specific DKK1 siRNA. RT-PCR and western blot
      analysis were used to determine the mRNA and protein levels of DKK1, beta-catenin
      and metalloproteinase 14 (MMP14) in siRNA-treated and -untreated cells. In
      addition, the invasion and migration of the EC cells were detected by invasion
      and migration assays. Transient transfection of DKK1 siRNA significantly
      inhibited the mRNA and protein levels of DKK1. Markedly increased cell invasion
      and migration was observed following treatment with DKK1 siRNA when compared with
      the negative control siRNA-treated and siRNA-untreated cells. The knockdown of
      DKK1 also elevated the mRNA and protein levels of beta-catenin and MMP14 involved
      in the Wnt signaling pathway, indicating that targeting this gene may promote
      intracellular Wnt signal transduction and thus, accelerate EC cell invasion and
      migration in vitro. The RNAi-mediated targeting of DKK1 gene expression in
      Ishikawa EC cells resulted in increased tumor cell invasion and migration. DKK1
      was identified as an inhibitor of EC cell invasion and migration via its novel
      role in the Wnt signaling pathway. Targeting DKK1 may therefore represent an
      effective anti-invasion and -migration strategy for the treatment of EC.

PMID- 24137407
TI  - Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide
      expression profiling.
AB  - The present study aimed to investigate the molecular basis of lung cancer
      development using a microarray to identify the differentially-expressed genes
      associated with the various tumor-node-metastasis (TNM) stages of lung
      adenocarcinoma. This subtype of lung cancer has increased in incidence within
      recent years in China. A 35K oligo gene array covering ~25,100 genes was used to
      screen the differentially-expressed genes among 90 lung adenocarcinoma samples of
      various TNM stages. To verify the data from the gene arrays, three genes [human
      zinc finger-containing, Miz1, PIAS-like protein on chromosome 7 (Zimp7), GINS
      complex subunit 2 (GINS2) and NSAID activated gene 1 (NAG-1)] were validated
      using quantitative (q)PCR in an alternative set of samples to the gene array. A
      total of 640 genes were identified that were differentially-expressed in lung
      adenocarcinoma compared with the surrounding normal lung tissues. From these 640
      candidate genes, 10 were observed to be differentially-expressed among TNM stages
      I, II and IIIA, of which, the Zimp7, GINS2 and NAG-1 genes were reported for the
      first time to be expressed at high levels in lung adenocarcinoma. The results of
      the qPCR for the three genes were consistent with those from the gene array. In
      total, 10 candidate genes were identified to be associated with the various TNM
      stages of lung adenocarcinoma in the population studied, which may provide new
      insights into the molecular basis underlying the development of lung
      adenocarcinoma and offer new targets for the diagnosis, therapy and prognosis.

PMID- 24137408
TI  - Differential microRNA expression in renal cell carcinoma.
AB  - The present study aimed to detect microRNA expression levels in the tissues and
      sera of patients with clear cell renal cell carcinoma (ccRCC). The association of
      microRNA expression with ccRCC clinical pathology was analyzed, and the potential
      of the microRNAs as ccRCC serum markers and the significance of their expression
      in the clinical diagnosis, staging, prognosis and selection of new therapeutic
      targets for ccRCC were discussed. Specific microRNAs were selected according to
      the associated literature. TaqMan quantitative polymerase chain reaction (qPCR)
      technology was used to determine the expression levels of selected microRNAs. miR
      34a, miR-224 and miR-21 were upregulated, whereas miR-141, miR-149 and miR-429
      were downregulated in the ccRCC tissues (P<0.01). The expression of miR-221 and
      miR-211 was not significant in the ccRCC tissues (P>0.05). miR-34a, miR-21 and
      miR-224 were upregulated and miR-141 was downregulated in the sera of patients
      with ccRCC (P<0.01), while the expression of miR-149 and miR-429 was not
      significant (P>0.05). The serum miR-21 expression levels were significantly
      correlated with the clinical staging of the patients with ccRCC (P<0.05). miR
      34a, miR-21 and miR-224 are upregulated in the tissues and sera of patients with
      ccRCC, whereas miR-141 is downregulated. miR-21 and miR-141 are associated with
      ccRCC and are, thus, potential ccRCC serum markers.

PMID- 24137409
TI  - Expression and clinical significance of cyclin kinase subunit 2 in colorectal
      cancer.
AB  - The overexpression of cyclin kinase subunit 2 (CKS2) is tightly correlated with
      tumor aggressiveness and prognosis in various malignancies, including gastric,
      breast, liver and prostate cancer. However, whether CKS2 is upregulated in
      colorectal cancer (CRC) remains unknown. The aim of the present study was to
      analyze CKS2 expression levels in CRC, and to determine the clinical diagnostic
      and prognostic values of CKS2 overexpression in CRC patients. CKS2 expression was
      analyzed at the mRNA and protein levels by quantitative (q)PCR and western blot
      analysis. CKS2 expression was significantly upregulated in CRC compared with the
      adjacent non-cancer and normal colorectal tissues. The overexpression of CKS2 was
      correlated with poor differentiation and the pathological stage. In addition,
      CKS2 overexpression was correlated with aggressive tumor progression in CRC,
      which indicated that CKS2 may serve as a good CRC biomarker.

PMID- 24137410
TI  - Microsurgical treatment for parasagittal meningioma in the central gyrus region.
AB  - The aim of the present study was to determine the efficacy of microsurgery
      treatment for parasagittal meningioma in the central gyrus region. A
      microsurgical technique was used to treat 26 patients with large parasagittal
      meningioma in the central gyrus region. The Rolandic and draining veins and the
      peritumoral normal brain tissue were retained, and the associated sagittal sinus
      was appropriately protected. A Simpson grade I, II or III resection was performed
      in 8 (30.8%), 12 (46.2%) and 6 (23.1%) patients, respectively, with no post
      operative mortalities. Following treatment, 9 patients exhibited hemiparalysis.
      No tumor recurrence was found in 21 patients during the follow-up examination.
      The treatment protocol described in the current study included sufficient pre
      operative imaging evaluations, a skilled microsurgical technique, improved
      protection of the Rolandic vein and treatment of the sagittal sinus, and was
      found to significantly increase the total tumor removal rate and decrease post
      operative recurrence.

PMID- 24137411
TI  - Identification of a mature cystic teratoma mimicking a presacral tumor by
      transsacral surgery in a young female: A case report.
AB  - The current case report presents an account of a unique surgical procedure
      performed to remove an extremely rare occurrence of a transsacral abdominal mass
      from a 24-year-old female. The patient presented with subtle sacrococcygeal pain
      for two months and a presacral abdominal mass derived from the right ovary. The
      mass was misdiagnosed as a presacral tumor based on the results of magnetic
      resonance imaging (MRI) performed prior to the surgery. The patient also
      exhibited the symptoms commonly caused by a presacral mass, however, during the
      surgery, the mass was not initially located under the sacrum. An ultrasound
      examination and an analysis of an intraoperative frozen section indicated that
      the mass was a mature cystic teratoma (MCT) of the ovary, located in the
      peritoneal cavity between the rectum and uterus. The mass was successfully
      resected and removed from the affected ovary through the abdominal cavity via the
      sacral region. A pathological examination of the tumor section confirmed a
      diagnosis of a MCT of the ovary.

PMID- 24137412
TI  - microRNA-199a is able to reverse cisplatin resistance in human ovarian cancer
      cells through the inhibition of mammalian target of rapamycin.
AB  - microRNAs (miRNAs/miRs) may have a crucial function in tumor metastasis through
      the regulation of a plethora of signaling pathways. Increasing evidence has shown
      that miR-199a is important in regulating the tumor metastasis of ovarian cancer,
      although the precise biological function of miR-199a is unclear at present. In
      the current study, it was observed that the expression levels of miR-199a were
      higher in OV2008 cells compared with C13* cells. However, lower levels of
      mammalian target of rapamycin (mTOR) protein were detected by western blotting in
      the OV2008 cells compared with the C13* cells. The miR-199a levels were increased
      in the C13* cells using miR-199a mimics and the mTOR levels were observed to
      decrease. This may have resulted in a reversal of cisplatin resistance in the
      C13* cells. To test this hypothesis, the Renilla luciferase reporter gene system
      was used to analyze the mTOR levels. The results indicated that the expression
      levels of mTOR were significantly blocked by the increased miR-199a levels. When
      the miR-199a inhibitor was applied to decrease the miR-199a levels, it was
      observed that the mTOR expression levels were increased, while cisplatin-induced
      apoptosis was decreased in the OV2008 cells. The study concludes that miR-199a is
      able to reverse cisplatin resistance in human ovarian cancer cells through the
      inhibition of mTOR and that mTOR may be the target of miR-199a during this
      process.

PMID- 24137413
TI  - miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1alpha
      expression in human ovarian cancer cells.
AB  - Drug resistance is a major problem encountered in the treatment of ovarian
      cancer. Previous studies have demonstrated that in several types of cancer the
      overexpression of the multidrug resistance 1 (MDR1) gene is mainly associated
      with drug resistance. The present study aimed to investigate the role of miR-21
      in the development of drug resistance in ovarian cancer cells. The expression
      levels of miR-21 in the ovarian cancer A2780 and A2780/taxol cell lines were
      detected by stem-loop real-time PCR. A2780 and A2780/taxol cells were transfected
      with mimics or inhibitors of miR-21 or negative control RNA. The expression
      levels of P-glycoprotein (P-gp) and hypoxia-inducible factor-1alpha (HIF-1alpha)
      proteins were assessed by western blot analysis. Drug sensitivity was analyzed by
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      expression levels of miR-21 and P-gp were upregulated to a greater extent in the
      paclitaxel-resistant ovarian cancer A2780/taxol cell line compared with the
      parental A2780 cell line. Transfection of A2780/taxol cells with inhibitors of
      miR-21 decreased the expression levels of the P-gp and HIF-1alpha proteins, and
      increased the sensitivity of the A2780/taxol cells to paclitaxel. The expression
      levels of P-gp were additionally increased; however, the sensitivity of the miR
      21 mimic-treated A2780 cells to paclitaxel was decreased. miR-21 may be involved
      in the development of drug resistance and the regulation of MDR1/P-gp expression,
      at least in part, by targeting HIF-1alpha in ovarian cancer cells.

PMID- 24137414
TI  - Tissue factor-targeted lidamycin inhibits growth and metastasis of colon
      carcinoma.
AB  - Colon cancer is the third most common cancer in the world. The overexpression of
      tissue factor (TF) in colon cancer cells makes it an ideal target for colon
      cancer therapy. The purpose of the present study was to develop a TF-targeting
      energized fusion protein, mlFVII-LDP-AE, which is composed of a mouse Factor VII
      light chain (mlFVII) as the targeting domain conjugated to the highly cytotoxic
      antibiotic lidamycin (LDM, LDP-AE) as the effector domain. The potential efficacy
      of mlFVII-LDP-AE for mouse colon cancer therapy was tested in a mouse colon
      cancer subcutaneous xenograft model and a live metastasis model in BALB/c mice.
      mlFVII-LDP-AE showed a tumor growth inhibition rate of 91.2% (at a dose of 0.8
      mg/kg) and a tumor metastasis inhibition rate of 84.7% (at a dose of 0.6 mg/kg).
      The results showed that mlFVII-LDP-AE was able to effectively inhibit the growth
      and metastasis of mouse colon cancer. As human TF and FVII have features similar
      to those of mice, human FVII light chain (hlFVII)-targeted LDM (hlFVII-LDP-AE)
      may be expected to have therapeutic potential for human colon cancer.

PMID- 24137415
TI  - Effects of gamma irradiation on cell cycle, apoptosis and telomerase activity in
      p53 wild-type and deficient HCT116 colon cancer cell lines.
AB  - Radiotherapy serves as adjunctive treatment to chemotherapy and surgical
      resection of colorectal cancer. However, the cellular response to irradiation
      varies depending on the expression of tumor suppressor p53, which plays a
      significant role in the regulation of cell cycle arrest, apoptosis and telomerase
      activity in various cancers. The present study aimed to investigate cell cycle
      arrest, apoptosis and telomerase activity with respect to p53 expression in p53
      wild-type (+/+) and deficient (-/-) HCT116 colon cancer cell lines following 5 Gy
      gamma-irradiation. Cell cycle arrest and apoptosis were evaluated using flow
      cytometry. The telomerase activity was measured using a TRAP (telomerase repeat
      amplification protocol) assay. Following treatment with irradiation, G1/S cell
      cycle arrest occurred in the p53+/+ cells, whereas the p53-/- cells accumulated
      in the G2 phase. No differences were observed in the apoptotic ratios between the
      two cell lines following irradiation. Decreased telomerase activity was observed
      in the p53+/+ cells, whereas telomerase activity was increased in the p53-/-
      cells. The results showed that while telomerase activity and G1 cell cycle arrest
      were regulated depending on the p53 status, G2 arrest and the apoptotic response
      were promoted via a p53-independent pathway.

PMID- 24137416
TI  - Functional analysis of human cancer-associated genes and their association with
      the testes and epididymis.
AB  - Human cancer-associated UniGene sets (NCBI GeneBank) provide a platform for
      identifying differentially-expressed genes in human cancers. The present study
      identified and characterized a set of human cancer-associated genes using the
      Digital Differential Display (DDD) and functional analysis tools. A total of
      1,904 genes were differentially expressed in 15 cancer types, including genes
      that had been previously shown to be specific in certain human cancers. A total
      of 274 genes were uniquely expressed in certain cancer types, including 37 genes
      that were highly expressed in the human testes and epididymis. These genes mainly
      functioned as ribosomal proteins, enzymes, receptors, secretory proteins and cell
      adhesion molecules. The most common domains that were encoded by the cancer
      associated genes were those of cytochrome P450 CYP2D6, serpin and apolipoprotein
      A-I. A further gene ontology (GO) enrichment analysis revealed seven major
      functional clusters, which corresponded to the enriched pathways involved in
      cancer. The present study provides a source of cancer-associated genes and their
      functions. The results provide new insights into cancer biology and the
      involvement of highly-expressed epididymal genes in cancer biomarkers.

PMID- 24137417
TI  - Scapular osteochondrolipoma: Imaging features with pathological correlation.
AB  - Osteochondrolipoma is an extremely rare histological variant of lipoma with
      osseous and cartilaginous differentiation. The present study reports an unusual
      case of an osteochondrolipoma occurring in the left scapular region of a 49-year
      old male. The physical examination revealed a 3-cm, hard, non-tender and
      minimally mobile mass. Plain radiography revealed a faintly ossified soft-tissue
      mass without evidence of bone erosion. Computed tomography (CT) confirmed the
      presence of a lesion and the normal appearance of the scapula. Magnetic resonance
      imaging (MRI) showed a well-circumscribed subcutaneous mass with an almost
      homogeneous high signal intensity on the T1- and T2-weighted sequences. Contrast
      enhanced fat-suppressed T1-weighted sequences demonstrated a faint peripheral and
      septal enhancement of the mass. A marginal excision of the tumor was performed.
      Histologically, the tumor was predominantly composed of mature adipocytes mixed
      with thin trabeculae of mature bone. In addition, small amounts of mature hyaline
      cartilage and osteoid were identified in the periphery of the lesion. Based on
      these findings, the tumor was diagnosed as an osteochondrolipoma. The patient
      demonstrated no evidence of local recurrence within six months of follow-up.
      Although rare, osteochondrolipoma should be considered as a differential
      diagnosis of a well-defined, calcified/ossified, subcutaneous mass in the
      scapular region.

PMID- 24137418
TI  - Somatostatin receptor subtypes 2 and 5 are associated with better survival in
      operable hepatitis B-related hepatocellular carcinoma following octreotide long
      acting release treatment.
AB  - Liver resections for hepatocellular carcinoma (HCC) in cirrhotic livers are
      associated with early recurrence and poor survival. Somatostatin analogues (SSAs)
      have been reported to inhibit cell proliferation by interacting with specific
      somatostatin receptors (SSTRs) 2 and 5. The present study investigated whether
      SSTR expression in HCC was associated with the clinical outcome following
      octreotide long-acting release (LAR) treatment. Paired tumor and cirrhotic liver
      samples were obtained following a liver resection from 99 patients with stage I
      II HCC and HBV-related cirrhosis. The expression of SSTR2 and 5 was assessed
      using quantitative (q)PCR and immunohistochemistry. The patients were classified
      into two groups, the high expression (n=47) and low expression (n=52) groups,
      based on the gene expression levels. The clinicopathological data and survival
      results of the two groups were compared. When compared with the surrounding
      cirrhotic tissue, the SSTR2 and 5 mRNA levels were significantly decreased in the
      HCC tissue. There were no significant differences between the groups with respect
      to the baseline characteristics. The tumor recurrence rate was significantly
      lower in the high expression group compared with that of the low expression group
      (63.83% vs. 82.69%; P=0.033). The 1-, 3- and 5-year disease-free and overall
      survival rates of the high expression group were 97, 89 and 71% and 98, 89 and
      74%, respectively. The survival time of the members of the high expression group
      was longer compared with that of the low expression group. The multivariate
      analysis revealed that the TNM-7 stage and SSTR2 expression were independent
      prognostic factors for survival. In conclusion, SSTR mRNA expression correlated
      with survival in patients with early-stage hepatitis B virus (HBV)-related HCC
      who were treated with octreotide LAR following surgery. The inhibitory effects of
      SSAs on tumor growth may be mediated by SSTR expression.

PMID- 24137419
TI  - Features of a giant cell tumour of the parotid gland: A case report.
AB  - A giant cell tumour (GCT) is a benign tumour that commonly arises in the distal
      end of the long bones. Extraosseous GCTs have been reported in a number of
      organs, but it is rare for a GCT to present in the parotid gland. Therefore,
      primary GCTs of the parotid gland (GCTPs) are extremely rare. Although GCTPs have
      been identified as benign soft-tissue tumours, they have a highly malignant
      potential and poor prognosis. In the present case, we report a 58-year-old male
      patient presenting with non-tender mass over the left preauricular area for 11
      months. The final pathology report revealed a rare case of a GCTP that was
      treated by parotidectomy and adjuvant radiation therapy. The patient had no
      recurrence after 2 years of follow-up.

PMID- 24137420
TI  - Unexpected pheochromocytoma presenting as a pancreatic tumor: A case report.
AB  - A 54-year-old female presented with a large pancreatic tumor of the tail during a
      regular physical examination. The patient underwent surgical intervention and the
      surgeon identified that the tumor originated from the retroperitoneal region.
      Markedly severe hemodynamic fluctuations occurred during the manipulation of the
      tumor and continued to occur subsequent to the tumor being removed. The vital
      signs were adequately managed and the surgery was successful without
      complications. The patient was discharged without any sequelae days later. The
      pathology report indicated a diagnosis of pheochromocytoma. Unexpected
      pheochromocytoma may lead to a fatal hypertensive crisis with catastrophic
      sequelae during surgery. The peri-operative management of pheochromocytoma
      remains a complicated challenge that requires intensive pre-operative preparation
      and vigilant peri-operative care. For surgeons and anesthesiologists who may
      encounter an unexpected hypertensive crisis during abdominal tumor surgery,
      undiagnosed pheochromocytoma should always be considered.

PMID- 24137421
TI  - Cytokine levels in abdominal exudate predict prolonged postoperative ileus
      following surgery for colorectal carcinoma.
AB  - The aim of the present study was to investigate whether the measurement of
      cytokines from abdominal exudate is valuable for the early diagnosis of prolonged
      postoperative ileus (PPOI) following colorectal surgery. In the present study,
      100 consecutive patients who were scheduled to undergo elective resection for
      carcinoma of the sigmoid or rectum were investigated. Abdominal exudate was
      obtained via a drain tube following surgery for the detection of interleukin (IL)
      1beta, IL-6 and tumour necrosis factor (TNF)-alpha. The correlation among the
      cytokine levels on postoperative days 1, 3 and 5 and the development of PPOI was
      investigated. Eight patients developed PPOI which was diagnosed 10-15 days
      postoperatively. No significant differences were observed among the peritoneal
      cytokine levels on postoperative days 1 and 3 in the 8 patients who developed
      PPOI when compared with those of the 92 patients that did not develop PPOI. By
      contrast, cytokine levels on postoperative day 5 were significantly higher in
      patients who developed PPOI when compared with those of patients that did not
      develop PPOI. The cytokine levels significantly increased during the first 5 days
      postoperatively in patients who developed PPOI and significantly decreased in
      patients who did not develop PPOI. The results of the present study showed that
      the increase in peritoneal IL-1beta, IL-6 and TNF-alpha levels may be an
      additional early diagnostic predictor of PPOI following colorectal surgery.

PMID- 24137422
TI  - Berberine enhances tumor necrosis factor-related apoptosis-inducing ligand
      mediated apoptosis in breast cancer.
AB  - Berberine (BBR) has been used for the treatment of bacterial and fungal
      infections and also for cancer-associated symptoms such as diarrhea. Furthermore,
      it has been reported that BBR may have direct antitumor effects. Although
      evidence supports the theory that tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) is a promising candidate for treating cancer, its usage
      may be limited due to the resistance to the TRAIL-induced apoptosis of cancer
      cells. In the present study, the effect of BBR on TRAIL-induced antitumor effects
      was investigated in vitro using recombinant TRAIL and in vivo using a 4T1 murine
      breast cancer model in combination with anti-DR5 (death-inducing TRAIL receptor)
      monoclonal antibody therapy. BBR sensitized human breast cancer cell lines to
      TRAIL-mediated apoptosis in vitro. The combination of BBR and recombinant TRAIL
      significantly activated caspase-3 and PARP cleavage in TRAIL-resistant MDA-MB-468
      cells. Furthermore, BBR in combination with TRAIL more effectively induced
      apoptosis compared with coptisine (COP), which is structurally related to BBR. In
      a murine 4T1 breast cancer model, BBR treatment enhanced the efficacy of anti-DR5
      antibody therapy against primary tumor growth and lung metastasis. Thus, BBR may
      become a new adjuvant for overcoming the resistance of cancer cells to TRAIL/DR5
      mediated therapy.

PMID- 24137423
TI  - Effects of 5-Aza-2'-deoxycytidine on the methylation state and function of the
      WWOX gene in the HO-8910 ovarian cancer cell line.
AB  - The aim of this study was to explore the effects of 5-Aza-2'-deoxycytidine (5-Aza
      CdR), a DNA methylation inhibitor, on the methylation state and function of the
      WWOX gene in the HO-8910 ovarian cancer cell line. The HO-8910 cells were divided
      into two groups, a control group and a 5-Aza-CdR-treated group. The methylation
      state of the WWOX gene was evaluated using a methylation-specific PCR assay. The
      effect of 5-Aza-CdR on the HO-8910 cells was analyzed using MTT and cell invasion
      assays, as well as flow cytometry. The animal models were established by
      intraperitoneal transplantation of the cells into nude mice. Following treatment
      with 5-Aza-CdR, a demethylation state was detected in the HO-8910 cells. WWOX
      protein expression was significantly higher in the 5-Aza-CdR-treated group
      compared with that in the control group. The cell growth rate at each tested time
      point and the number of invasive cells were lower in the 5-Aza-CdR-treated group
      compared with that in the control group. Flow cytometry revealed that 67.13% of
      the cells were arrested at the G0/G1 stage in the 5-Aza-CdR-treated group. The
      tumorigenic ability of the 5-Aza-CdR-treated group was lower compared with that
      of the control group. In conclusion, the methylation state of the WWOX gene in HO
      8910 cells may be reversed using 5-Aza-CdR, which may also inhibit the growth of
      these cells.

PMID- 24137424
TI  - An effective approach for treating unresectable hepatoblastoma in infants and
      children: Pre-operative transcatheter arterial chemoembolization.
AB  - The objective of the present study was to investigate the feasibility and
      efficacy of pre-operative transcatheter arterial chemoembolization (TACE) for
      unresectable hepatoblastoma in infants and children. A total of 24 patients (14
      males and 10 females) with unresectable hepatoblastoma, aged between 26 days and
      41 months, were treated with pre-operative TACE between March 2007 and March
      2011. All cases were confirmed by computed tomography (CT) and liver tumor biopsy
      prior to TACE. Arteriography was performed and the chemoembolization mixture
      (pirarubicin and cisplatin emulsified in lipiodol) was injected, followed by
      polyvinyl alcohol (PVA). The procedure was performed one to four times depending
      on the patient's response. There was a significant reduction in tumor volume
      associated with decreased alpha-fetoprotein (AFP) levels following TACE. Tumor
      volumes decreased by between 46.1 and 90.2%, with a mean value of 72%. The AFP
      levels fell by between 63.8 and 99.9%, with a mean value of 95.7%. A total of 22
      cases underwent subsequent safe complete surgical resection and the remaining two
      patients accepted a partial resection. To evaluate the toxicity of TACE, the
      alanine aminotransferase (ALT), serum creatinine (Cr) and creatine kinase (CK)
      levels of the patients were measured to assess liver, renal and cardiac function,
      respectively. The results showed that no marked chemotherapeutic agent-induced
      toxicity occurred during TACE. It may be concluded that TACE is an effective and
      feasible pre-operative therapeutic approach for treating unresectable
      hepatoblastoma and that it may improve the resectability of bulky liver tumors.

PMID- 24137425
TI  - A novel taspine derivative suppresses human liver tumor growth and invasion in
      vitro and in vivo.
AB  - Taspine is an attractive target of research due to the anticancer and anti
      angiogenic effects shown by in vitro and in vivo experiments. The present study
      investigated the role of tas1611, which is a derivative of taspine that has
      increased activity and solubility, in the regulation of the invasive properties
      of the SMMC-7721 liver cell line in vitro and in tumor inhibition in vivo. The
      proliferation of the SMMC-7721 cells was examined using the tetrazole blue
      colorimetric method. Matrigel(r) invasion chamber assays and zymogram analyses
      were performed to assess the inhibitory effect of tas1611 on cell invasion.
      Finally, a solid tumor athymic mouse model was employed to further investigate
      the anti-tumor effect of this compound. The results revealed that tas1611 had a
      marked inhibitory effect on the invasion of the SMMC-7721 cells and that this
      effect was associated with the activity and expression levels of matrix
      metalloproteinase (MMP)-2 and MMP-9. Furthermore, tas1611 was able to inhibit
      tumor growth effectively in a solid tumor SMMC-7721 athymic mouse model. In
      conclusion, tas1611 may serve as a promising novel therapeutic candidate for the
      treatment of metastatic liver cancer.

PMID- 24137426
TI  - Inhibition of the enzyme activity of cytochrome P450 1A1, 1A2 and 3A4 by
      fucoxanthin, a marine carotenoid.
AB  - Fucoxanthin is a carotenoid that is mainly identified in brown algae and is known
      to have anticarcinogenic and anti-tumor activities. Carotenoids have generally
      been shown to induce the expression and enzyme activity of the cytochrome P450s
      (CYPs). The present study evaluated the effect of fucoxanthin on the expression
      and enzymatic activity of the major xenobiotic metabolizing enzymes, CYP1A1,
      CYP1A2 and CYP3A4. Fucoxanthin markedly induced the expression of cyp1a1 mRNA in
      HepG2 cells, but inhibited its enzyme activity in the cells and in vitro.
      Fucoxanthin also inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose
      dependent manner in vitro. These results suggest that fucoxanthin may serve as a
      useful agent in cancer prevention with less adverse effects than beta-carotene,
      including the activation of pro-carcinogens by CYPs.

PMID- 24137427
TI  - Two rare cases of a solid pseudopapillary neoplasm of the pancreas.
AB  - A solid pseudopapillary neoplasm (SPN) of the pancreas has distinct
      histopathological features. A solid pattern of growth with pseudopapillary
      structures that result from degeneration is observed. On rare occasions, the
      tumor may vary from being entirely solid to completely cystic. The present study
      describes two unique cases of SPN. A 25-year-old male presented with a pancreatic
      tumor showing a predominantly solid pattern with no degenerative change, although
      the pre-operative cytological specimens that were obtained by endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA) revealed pseudopapillary
      structures. The second case was of an 11-year-old female who presented with a
      pancreatic tumor with prominent degeneration. Nests and cords of the remaining
      neoplastic cells were located only at the periphery, with perineural invasion. An
      immunohistochemical analysis revealed that the tumor cells in the two cases were
      positive for CD10 and beta-catenin and negative for trypsin. An awareness of the
      broad morphological variability of SPN and an immunohistochemical panel that
      includes CD10, beta-catenin and trypsin are useful for establishing an accurate
      diagnosis.

PMID- 24137428
TI  - Cytotoxic effects of caffeic acid undecyl ester are involved in the inhibition of
      telomerase activity in NALM-6 human B-cell leukemia cells.
AB  - Our previous study reported that caffeic acid undecyl ester (CAUE) has a potent
      cytotoxic effect and induces apoptosis in NALM-6 cells, but not in normal human
      lymphocytes. The majority of normal human cells have no detectable telomerase
      activity, however, activity is commonly detected in cancer cells. Thus,
      inhibiting telomerase activity and inducing apoptosis may have a selective effect
      on cancer cells. The aim of the present study was to investigate the inhibitory
      effects of telomerase activity by CAUE in a NALM-6 cell culture system. CAUE was
      shown to preferentially damage DNA synthesis compared with RNA or protein
      synthesis. In addition, telomerase activity was significantly suppressed and the
      activity of human telomerase reverse transcriptase (hTERT), a subunit of
      telomerase, was decreased following treatment with CAUE, each in a concentration
      dependent manner. These results indicated that the cytotoxic effects of CAUE are
      mediated by the inhibition of DNA synthesis and telomerase activity. The present
      study is the first to identify the cytotoxic mechanisms of CAUE in leukemia
      cells.

PMID- 24137429
TI  - Cutaneous squamous cell carcinoma in a patient with neurofibromatosis type 1: A
      case report.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease that is
      characterized by the presence of multiple neurofibromas, cafe-au-lait spots and
      iris hamartomas. It is well established that the incidence of tumors in patients
      with NF1 is high compared with the normal population and that the majority of the
      tumors are non-epithelial neoplasms, including neurofibromas, malignant
      peripheral nerve sheath tumors, gliomas and leukemia. Studies have suggested that
      patients with NF1 also have a significantly higher risk of certain types of
      carcinomas. However, the occurrence of cutaneous squamous cell carcinoma (SCC) in
      a patient with NF1 is extremely rare. The present study describes the second
      documented case of a cutaneous SCC adjacent to a neurofibroma of the forehead
      with histopathological analyses in a patient with NF1. An 80-year-old female with
      NF1 presented with a rapidly growing skin tumor of the forehead.
      Histopathological study of the resected forehead tumor demonstrated that there
      were two tumorous lesions. One was an invasive SCC and the other was a
      neurofibroma. The lesions were adjacent, but no continuity was present. NF1 is
      caused by inactivating mutations in the NF1 gene and loss of heterozygosity of
      this gene has been reported in neurofibromas, malignant peripheral nerve sheath
      tumors, gliomas and pheochromocytomas in patients with NF1. However, the genetic
      mechanism of carcinoma development in patients with NF1 is not well understood.
      Studies have suggested the role of the NF1 and/or the BRCA gene in the occurrence
      of breast cancer. Additional studies are required to elucidate these mechanisms.

PMID- 24137430
TI  - Safety of nanoparticle albumin-bound paclitaxel administered to breast cancer
      patients with clinical contraindications to paclitaxel or docetaxel: Four case
      reports.
AB  - Taxanes, including paclitaxel (PTX) and docetaxel (DOC), are poorly soluble in
      water due to their hydrophobic properties and thus, require solvents. However,
      use of these solvents has been associated with toxic responses, including a
      hypersensitivity reaction (HSR). Nanoparticle albumin-bound paclitaxel (nab-PTX)
      is a novel formulation of PTX, which allows reconstitution of the agent with a
      saline solution instead of solvents and administration without premedication for
      HSRs. The current study reports the safe administration of nab-PTX to four breast
      cancer patients considered clinically to have contraindications to PTX or DOC.
      Two of the patients had previously experienced HSRs to PTX or DOC and the other
      two patients had contraindications to steroids as a premedication for HSRs, since
      one patient suffered from diabetes and the other was a carrier of the hepatitis B
      virus. All 4 patients were safely administered nab-PTX. In conclusion,
      administration of nab-PTX appears to be effective for patients that have
      previously experienced HSRs to other taxanes or in those with contraindications
      to steroids.

PMID- 24137431
TI  - Oleanolic acid inhibits proliferation and induces apoptosis in NB4 cells by
      targeting PML/RARalpha
AB  - Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid contained in
      a variety of plant species, exhibits broad biological properties, including
      anticancer effects. Acute promyelocytic leukemia (APL) is a distinct subtype of
      acute myeloid leukemia. APL has a unique and specific chromosomal aberration,
      t(15;17), which results in the formation of a fusion gene and protein
      PML/RARalpha, which is not only necessary for the diagnosis of APL, but is also
      critical for APL pathogenesis. In the present study, the cytotoxic effect of OA
      on NB4 cells was investigated. Cell viability was assessed via the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression
      levels of bax and bcl-2 mRNA were determined by quantitative PCR. Apoptosis was
      analyzed using DNA fragment analysis and cell cycle distributions were analyzed
      by flow cytometry. The activity of caspase-3 and caspase-9 was determined by
      colorimetric assays. The expression of the PML/RARalpha fusion protein was
      analyzed by western blotting. The MTT assay showed that OA inhibited the
      proliferation of the NB4 cells. The expression levels of pro-apoptotic bax mRNA
      were increased and the levels of anti-apoptotic bcl-2 mRNA were decreased
      following the treatment of the NB4 cells with OA at 80 MUmol/l. Treatment of the
      NB4 cells with OA at 80 MUmol/l induced apoptosis and G1 phase arrest, while
      caspase-9 and caspase-3 activity was significantly increased. Furthermore, the
      expression of the PML/RARalpha fusion protein was decreased. Together, these data
      suggest that OA exerts a cytotoxic effect that inhibits proliferation and induces
      apoptosis in NB4 cells by targeting PML/RARalpha, making it a potent therapeutic
      agent against leukemia.

PMID- 24137432
TI  - Significantly increased expression of OCT4 and ABCG2 in spheroid body-forming
      cells of the human gastric cancer MKN-45 cell line.
AB  - The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor
      formation, recurrence and metastasis. Key to the study of CSCs is their isolation
      and identification. The present study investigated whether spheroid body-forming
      cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC
      properties, and also assessed the expression of the candidate CSC markers,
      octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding
      cassette transporter G2 (ABCG2) in the MKN-45 spheroid body cells. The MKN-45
      cells were plated in a stem cell-conditioned culture system to allow for spheroid
      body formation. The expression levels of OCT4 and ABCG2 in the spheroid body
      cells were assessed by qPCR, western blot analysis and immunofluorescence
      staining, while the tumorigenicity of the spheroid body-forming cells was
      assessed by in vivo xenograft studies in nude mice. The MKN-45 cells were able to
      form spheroid bodies when cultured in stem cell-conditioned medium. The spheroid
      body-forming cells showed a significantly higher (P<0.01) expression of OCT4 and
      ABCG2 compared with the parental cells. These data suggest that the spheroid body
      cells from the MKN-45 GC cell line cultured in stem cell-conditioned medium
      possessed gastric CSC properties. The co-expression of OCT4 and ABCG2 by these
      cells may represent the presence of a subpopulation of gastric CSCs.

PMID- 24137433
TI  - Repeat stereotactic radiosurgery in the management of brain metastases from
      NSCLC: A case report and review of the literature.
AB  - The aims of radiotherapeutic treatment of brain metastases include maintaining
      neurocognitive function and improvement of survival. Based on these premises, we
      present a case report in which the role of repeat stereotactic radiosurgery (SRS)
      was investigated in a patient with a recurrent brain metastasis from non-small
      cell lung cancer in the same area as previously treated with radiosurgery. A 40
      year-old male caucasian patient was diagnosed with brain metastasis from non
      small cell lung cancer (NSCLC) and underwent SRS. The patient developed a
      recurrence of the disease and a second SRS on the same area was performed. After
      8 months, tumor restaging demonstrated a lesion compatible with a recurrence and
      the patient underwent surgery. Histological diagnosis following surgery revealed
      only the occurrence of radionecrosis. Radiotherapy was well-tolerated and no
      grade 3/4 neurological toxicity occurred. To date, no consensus exists on the
      efficacy of retreatment with SRS. Despite the limited number of studies in this
      field, in the present case report, we outline the outcomes of this unconventional
      approach.

PMID- 24137434
TI  - Protective effect of tanshinone IIA against radiation-induced ototoxicity in HEI
      OC1 cells.
AB  - Radiotherapy is a highly efficient treatment method for nasopharyngeal carcinoma
      that is often accompanied by significant ototoxic side-effects. The inner ear
      hair cells are particularly prone to serious injury following radiotherapy.
      Tanshinone IIA is a transcription factor inhibitor that is extracted from the
      traditional herbal medicine, Salvia miltiorrhiza Bunge. The present study
      investigated the effects of tanshinone IIA treatment on radiation-induced
      toxicity in the HEI-OC1 hair cell line. Using an MTT assay and flow cytometry,
      the radiation-induced weakening of the cells was observed to be alleviated when
      the cells were pre-treated with tanshinone IIA. Radiation exposure promoted
      p65/nuclear factor (NF)-kappaB nuclear translocation and activated the p53/p21
      pathway, two processes which play a significant role in radiation-induced cell
      apoptosis. However, pre-treatment of the cells with tanshinone IIA inhibited
      p65/NF-kappaB nuclear translocation and p53/p21 pathway activation. These results
      demonstrate that tanshinone IIA is capable of protecting cochlear cells from
      radiation-induced injury through the suppression of p65/NF-kappaB nuclear
      translocation and the p53/p21 signaling pathway.

PMID- 24137435
TI  - Recurrence and histological evolution of dysembryoplastic neuroepithelial tumor:
      A case report and review of the literature.
AB  - Studies of recurrent dysembryoplastic neuroepithelial tumors (DNTs) are
      distinctly rare. The present study reports the case of a 15-year-old female with
      a temporal lobe DNT, which recurred and transformed into an astrocytoma (WHO
      grade II) five years after an initial gross total resection (GTR). Furthermore,
      all the previous studies on recurrent DNT are reviewed. Although the majority of
      DNT cases demonstrate benign behavior, recurrent DNTs have been observed
      following a GTR of the tumor. Patients do not appear to benefit from post
      operative adjuvant therapy, and inappropriate radiotherapy or chemotherapy may
      result in tumor recurrence or malignant transformation. The prognosis is
      favorable if a GTR of the recurrent tumor is achieved. The use of regular imaging
      examinations and the maintenance of a long-term follow-up is of importance
      following a tumor resection.

PMID- 24137436
TI  - Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in
      the human cholangiocarcinoma CCKS-1 cell line.
AB  - Epidermal-mesenchymal transition (EMT) confers an advantage to cancer cells by
      improving their invasive capacity and metastatic potential. This phenomenon by
      which epidermal cells change into mesenchymal cells and therefore acquire a
      higher ability to automaticity, is considered a key process in cancer
      development. Transforming growth factor-beta (TGF-beta) is a significant factor
      for accelerating EMT through the activation of proteins, including members of the
      Smad pathway. Furthermore, previous studies have shown that low-dose paclitaxel
      (PTX) inhibits EMT in certain cell lines, including those of cancer cells. The
      present study determined whether low-dose PTX was able to inhibit EMT in a human
      cholangiocarcinoma CCKS-1 cell line that had been treated with TGF-beta1. First,
      the cytotoxic concentration of PTX for the CCKS-1 cells was identified to be ~5
      nM by MTT assay and dead cell staining. Therefore, the concentrations of PTX were
      set as 1 nM, 2.5 nM and 5 nM for the subsequent experiments. In the morphological
      investigation, the CCKS-1 cells changed into a spindle morphology and became
      separated by the administration of TGF-beta1. However, low-dose PTX inhibited
      these changes and the morphology resembled the control cells in a dose-dependent
      manner. Similarly, immunofluorescence and immunoblotting investigations revealed
      that the CCKS-1 cells expressed mesenchymal markers following the administration
      of TGF-beta1. However, low-dose PTX inhibited the expression of the mesenchymal
      markers and the CCKS-1 cells expressed the epithelial marker, E-cadherin. In
      particular, a concentration-dependent effect was observed in the immunoblotting
      experiments. These results show that PTX may be able to inhibit EMT in cancer
      cells, depending on the dose concentration.

PMID- 24137437
TI  - ID1 regulates U87 human cell proliferation and invasion.
AB  - Despite therapeutic advances, the prognosis of patients diagnosed with malignant
      glioma has not improved in recent years. In particular, the molecular mechanisms
      that mediate glioma invasion remain poorly understood. The importance of ID1 in
      promoting tumor invasion and metastasis has recently emerged and a role for ID1
      as a possible molecular marker of tumor aggressiveness has been proposed. To
      investigate the biological function of ID1 in glioblastomas, ID1-silenced U87
      glioblastoma multiforme (GBM) cells were constructed using a small hairpin RNA
      (shRNA) sequence. The effect of the knockdown of ID1 on proliferation and
      invasion in these cells was analyzed using the 5-bromo-2'-deoxy-uridine cell
      proliferation, Transwell invasion, scratch and cell adhesion assays. Compared
      with the controls, the U87 cells expressing ID1-shRNA exhibited a significantly
      decreased proliferation and invasion capacity (P<0.05), as well as increased cell
      adhesion. Furthermore, silencing ID1 reduced the expression of c-Myc, cyclin D1
      and beta-catenin, while increasing E-cadherin expression in U87 cells. This study
      showed that ID1 regulates the metastatic potential of GBM cells by controlling
      the epithelial-mesenchymal transition. Therefore, ID1 is a potential prognostic
      indicator and therapeutic target in glioblastomas.

PMID- 24137438
TI  - Lentivirus-mediated LIGHT overexpression inhibits human colorectal carcinoma cell
      growth in vitro and in vivo.
AB  - Human LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein
      D binding to herpesvirus entry mediator on T cells) is the 14th member of the
      tumor necrosis factor (TNF) superfamily and is therefore also known as TNFSF14.
      LIGHT has been proven to be a multifunctional molecule affecting cell
      proliferation, differentiation and a number of other biological processes, in
      particular, cell growth inhibition. However, the expression and molecular
      mechanisms of the LIGHT gene in human colorectal carcinoma cells remain largely
      unclear. In the present study, the LIGHT gene was overexpressed using a
      lentiviral expression vector in HCT116 human colorectal carcinoma cells in vitro
      and in vivo, in order to explore the mechanism by which the LIGHT gene inhibits
      cell growth and suppresses tumor formation. The results showed that the
      recombinant lentivirus with LIGHT overexpression inhibited the proliferative
      capacity of the HCT116 cells and significantly decreased the xenografted tumor
      volumes in nude mice. Furthermore, LIGHT treatment effectively initiated
      increased caspase-3 and decreased Bcl-2 activities in the HCT116 cells. This
      study provides a basis for the improved understanding of the role and molecular
      mechanisms of the LIGHT gene in human colorectal carcinoma cells and may
      facilitate further functional studies of LIGHT.

PMID- 24137439
TI  - Inhibition of tumor growth and histopathological changes following treatment with
      a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model.
AB  - The stromal derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor
      aggressiveness and metastasis in prostate cancer. The present study aimed to
      explore the potential therapeutic effects of a CXCR4 antagonist in prostate
      cancer. The effect of SDF-1 and a CXCR4-specific antagonist, AMD3100, on human
      prostate cancer PC-3 cell proliferation and protein kinase B (Akt) signaling was
      assessed. Moreover, a PC-3 tumor xenograft model was used to evaluate the effect
      of AMD3100 on tumor growth and to identify the histopathological changes and
      immunohistochemical differences between AMD3100-treated and untreated groups.
      Cell proliferation was not significantly affected by SDF-1 or AMD3100 treatment
      in vitro. Western blot analysis revealed that SDF-1 stimulation enhanced the
      expression of phosphorylated Akt in the PC-3 cells, but that the SDF-1-induced
      expression of phosphorylated Akt was abrogated in the AMD3100-treated PC-3 cells.
      In the PC-3 tumor xenograft model, AMD3100 significantly inhibited tumor growth,
      while AMD3100-treated PC-3 tumors had lower levels of microvessel formation and a
      lower immunoreactivity for the proliferation marker Ki-67 and the anti-apoptotic
      marker Bcl-2 compared to control tumors in vivo. The CXCR4-specific antagonist
      inhibits SDF-1-induced CXCR4/Akt signal transduction, and effectively suppresses
      tumor growth in the PC-3 xenograft model. The present study indicates that CXCR4
      targeting may represent a novel strategy for the treatment of castration
      resistant prostate cancer (CRPC).

PMID- 24137440
TI  - Photodynamic therapy combined with cryotherapy for the treatment of nodular basal
      cell carcinoma.
AB  - Carbon dioxide (CO2) laser ablation in combination with photodynamic therapy
      (PDT) has previously been successfully used to treat superficial basal cell
      carcinoma (BCC). However, the efficacy of this treatment modality is limited in
      the treatment of deeper lesions and the more aggressive subtypes of BCC. In order
      to improve the outcome of PDT, 8 BCC lesions of variable depths (4 lesions <=2 mm
      and 4 lesions >2 mm) and subtypes (1 superficial, 6 nodular and 1 infiltrative)
      were treated with CO2 laser ablation in combination with PDT, followed by
      modified cryotherapy. The mean number of treatment sessions was 1.5 and the
      follow-up period was 22 months. All of the patients demonstrated a complete
      response and no recurrence of disease, while the majority of patients were
      satisfied with the cosmetic results upon follow-up examination. The combination
      therapy of CO2 laser ablation with PDT followed by modified cryotherapy
      demonstrated a good efficacy and satisfactory cosmetic outcomes in the treatment
      of nodular BCC.

PMID- 24137441
TI  - Mature teratoma of the spinal cord in adults: An unusual case.
AB  - Intraspinal mature teratomas rarely occur in adults. The present study describes
      an unusual case of adult intradural mature teratoma, which was completely
      resected. A 22-year-old female presented with an intermittent pinching pain in
      the lower right shank that had lasted for three months. Magnetic resonance
      imaging (MRI) results indicated a multicystic mass extending from the T12 to L2
      vertebrae, and the tumors were certified as teratomas by a histopathological
      examination. The level of pain experienced by the patient was improved following
      the surgery. The present study also compared the literature concerning adult
      intradural mature teratoma, summarized the basic clinical characteristics and
      theory of origin of adult intradural mature teratoma and reviewed the available
      treatments for this disease.

PMID- 24137442
TI  - An extragastrointestinal stromal tumor originating from the seminal vesicles: A
      case report and review of the literature.
AB  - The present study reports a case of an extragastrointestinal stromal tumor
      (EGIST) originating from the seminal vesicles. A 74-year-old male patient with a
      tumor in the seminal vesicles underwent a radical spermatocystectomy due to an
      increased defecation frequency and a huge mass in the seminal vesicles.
      Ultrasonography and computed tomography (CT) initially diagnosed the mass as a
      tumor originating from the prostate. However, the mass was ultimately confirmed
      as an EGIST from the seminal vesicles following a laparotomy. According to the
      size, mitotic activity, cellularity, necrotic situation and immunohistochemical
      data, the tumor belonged to a low-risk group. No recurrence or metastasis has
      been identified during six years of follow-up observations. To the best of our
      knowledge, this is the first study to report this particular pathological type of
      EGIST.

PMID- 24137443
TI  - Doppler ultrasonography reveals blood flow signals within the masses of invasive
      moles in subjects with normal hCG levels after chemotherapy: Three case reports.
AB  - A consensus has formed that patients with invasive moles should continue with one
      to three cycles of chemotherapy after human chorionic gonadotropin (hCG) levels
      have decreased to a normal level. However, the management plan has not been
      agreed for cases where Doppler ultrasonography (DU) indicates blood-flow signals
      within the tumor mass after one to three cycles of chemotherapy when the hCG
      concentration has returned to normal. The present study describes the clinical
      and therapeutic courses of three patients with invasive moles with confirmed
      blood-flow signals (by DU) after their hCG levels had normalized. One patient
      underwent surgery to remove the mass within the uterine muscle, while the other
      two patients decided to cease chemotherapy and were managed by follow-up
      appointments; all three patients had good outcomes. These data illustrate that
      patients with invasive moles should be followed up if DU indicates blood-flow
      signals in the tumor mass after one to three cycles of chemotherapy when the hCG
      level has decreased back to a normal level.

PMID- 24137444
TI  - MicroRNA-375 targets the 3-phosphoinositide-dependent protein kinase-1 gene in
      pancreatic carcinoma.
AB  - Pancreatic carcinoma (PC) is an aggressive malignancy with one of the poorest
      mortality rates. It is the sixth leading cause of mortality from malignant
      disease in China and the fourth leading cause of cancer-related mortality in the
      United States. The poor outcome reflects the requirement for an improved
      understanding of the transcriptional control of oncogenic signaling pathways. 3
      phosphoinositide-dependent protein kinase-1 (PDK1) is a potent oncogenic driver
      of PC. The present study aimed to elucidate the transcriptional regulation of
      microRNA (miR)-375-targeted PDK1. miR-375 is a putative target and, in the
      present study, was observed to be significantly downregulated in the tumor
      compared with non-tumor tissues from patients with PC (n=44). As determined by a
      luciferase reporter assay, the ectopic expression of miR-375 was identified to
      diminish the transcriptional activity of PDK1. Furthermore, immunoblotting
      revealed that miR-375 suppressed endogenous PDK1 protein levels. Functional
      assays showed that miR-375 was able to inhibit proliferation and promote
      apoptosis of the PC cells. miR-375 is a significant regulator of the PDK1
      oncogene, suggesting that it may have a potential therapeutic role in the
      treatment of PC.

PMID- 24137445
TI  - Peliosis hepatis mimicking cancer: A case report.
AB  - Peliosis hepatis (PH) is a rare condition characterized by the presence of blood
      filled cavities within the liver. The etiology of PH remains unknown, but it has
      been reported to be associated with infections or malignancies. However, the
      cause of PH is not clear in 20-50% of patients. The current study presents the
      case of a 19-year-old male who presented with right upper quadrant pain that had
      lasted for three days. The patient was a student with no previous medical
      history. Contrast-enhanced computer tomography (CT) and ultrasonography showed a
      neoplasm in the right liver and a diagnosis of primary liver cancer was made due
      to the manifestation of the disease and the results of physical tests. The
      individual was treated successfully with an irregular right hemihepatectomy and
      was in good health at 6-months post-surgery. A tissue specimen was obtained and
      determined to be PH by pathological examination and immunohistochemistry
      analysis. Consequently, a diagnosis of PH must be considered in cases like this.

PMID- 24137446
TI  - Gene expression of WWOX, FHIT and p73 in acute lymphoblastic leukemia.
AB  - The aim of the present study was to analyze the expression of WW-domain
      oxidoreductase (WWOX), fragile histidine triad (FHIT) and p73 in acute
      lymphoblastic leukemia (ALL). Samples from 122 ALL patients and 35 non-ALL
      control patients were collected in this study. RT-PCR was performed to detect the
      mRNA expression of WWOX, FHIT and p73. The methylation status of the WWOX
      promoter region, FHIT promoter region and the first exon region of p73 were also
      analyzed using the methylation-specific PCR method. The mRNA expression of WWOX,
      FHIT and p73 was significantly lower in the ALL samples compared with the
      controls (48.2, 42.9 and 55.4%, respectively). By contrast, the methylation
      frequency of WWOX, FHIT and p73 was significantly higher in the ALL samples
      compared with the controls (44.6, 46.4 and 37.5%, respectively). The mRNA
      expression of these three genes was inversely correlated with the methylation
      frequency in the ALL samples (correlation coefficients, -0.661, -0.685 and -0.536
      for WWOX, FHIT and p73, respectively). Moreover, the mRNA expression of WWOX was
      positively correlated with that of FHIT and p73 (correlation coefficients, 0.569
      and 0.556, respectively). However, the methylation status of WWOX had no
      correlation with that of FHIT or p73. It was concluded that the high methylation
      status of WWOX, FHIT and p73 may lead to the inactivation of expression and the
      silencing of these genes, promoting the occurrence and development of ALL. The
      determination of the mRNA expression and methylation status of WWOX, FHIT and p73
      may aid in the development of treatment approaches for ALL.

PMID- 24137447
TI  - Inhibitory effects of tamoxifen and doxorubicin, alone and in combination, on the
      proliferation of the MG63 human osteosarcoma cell line.
AB  - The present study aimed to compare the combined effect of tamoxifen (TAM) and
      doxorubicin (ADM) with the individual effects of TAM and ADM alone on the MG63
      human osteosarcoma cell line. Estrogen receptor (ER) expression was detected in
      the MG63 cells using reverse transcription PCR. The morphological changes during
      the inhibition of cell growth were observed using an inverted microscope and a 3
      (4, 5-dimethy1-2-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT)
      colorimetric assay following the individual or combined addition of TAM and ADM.
      ERalpha and ERbeta expression was detected in the MG63 cells. The typical
      apoptotic cell morphology was observed in all groups, with the exception of the
      control group. The MTT colorimetric analysis demonstrated that the rate of
      inhibition of cell proliferation in the combination group was significantly
      increased compared with that in the other groups (P<0.05). ERalpha and ERbeta
      expression was detected in the MG63 human osteosarcoma cells. TAM and ADM alone
      were able to inhibit cell proliferation. The combination of TAM and ADM
      significantly enhanced the inhibitory effect, partly through the enhanced
      sensitivity of the cells to ADM by TAM, which caused the inhibition of cell
      proliferation and apoptosis.

PMID- 24137448
TI  - Osseous metaplasia with mature bone formation of the thyroid gland: Three case
      reports.
AB  - Nodular hyperplasia (nodular or multinodular goiter) is the most common form of
      thyroid disease. These nodules may undergo secondary changes in the form of
      hemorrhages, calcification and cystic degeneration. However, osseous metaplasia
      with mature bone formation rarely occurs. The present study reports the cases of
      three female patients with thyroid nodules diagnosed as nodular hyperplasia with
      osseous metaplasia and mature bone formation. The patients underwent right
      lobectomy, near total thyroidectomy and total thyroidectomy, respectively. The
      clinical course of the patients following resection were unremarkable.

PMID- 24137449
TI  - Molecular pathological study of the human nasopharyngeal carcinoma CNE3 cell
      line.
AB  - The present study aimed to identify the molecular pathological changes of the
      nasopharyngeal carcinoma (NPC) epithelial CNE3 cell line, which has been used in
      experimental studies for 20 years in a culture environment. The pathological type
      of NPC and the presence of the Epstein-Barr virus (EBV) were identified. CNE3
      short tandem repeats (STRs) were amplified, analyzed and compared using
      metastatic carcinoma tissue from primary NPC. Immunohistochemistry (IHC) and in
      situ hybridization (ISH) were used to identify the immunophenotype and EBV
      encoded small RNA (EBER) expression in nude mice transplanted CNE3 tumor cells.
      Polymerase chain reaction (PCR) and DNA sequencing were used to identify the EBV
      oncogene, BamH1-A right frame 1 (BARF1) and electron microscopy was used to
      analyze the organization of the ultrastructure. CNE3 was not cross-contaminated
      by other human cell lines and the EBV was no longer present in the CNE3 cells.
      The pathological type of CNE3 was transformed from an undifferentiated non
      keratinizing carcinoma with focal adenocarcinoma differentiation into a poorly
      differentiated adenocarcinoma. In conclusion, this knowledge on the molecular
      pathological changes of CNE3 may aid in the development of new research
      approaches for NPC.

PMID- 24137451
TI  - An abdominal extraskeletal osteosarcoma: A case report.
AB  - Primary abdominal extraskeletal osteosarcoma (EOS) is a rare carcinoma. The
      present study reports a case of a primary abdominal EOS involving the greater
      omentum and also presents a review of the literature on the etiology, diagnosis,
      differential diagnosis, pathological features, treatment and prognosis of the
      disease. The patient in the present study underwent laparoscopic surgery. A
      pathological examination revealed that the tumor tissues contained malignant and
      primitive spindle cells with varying amounts of neoplastic osteoid and osseous or
      cartilaginous tissue. The post-operative follow-up appointments were scheduled at
      three-month intervals for two years. The tumor recurred three months after the
      surgery.

PMID- 24137450
TI  - Treatment of an Askin tumor: A case report and review of the literature.
AB  - Askin tumors are rare malignant neoplasms that are localized in the
      thoracopulmonary region and mainly occur in children and adolescents. Further
      investigation with regard to the effective treatment of this disease is required,
      since the disease has a low incidence and limited knowledge is available on the
      biological activity and prognostic factors of this type of tumor. The present
      study describes the case of a 30-year-old male patient with a histologically and
      morphologically proven Askin tumor who was treated in Shandong Cancer Hospital
      and Institute (Jinan, China). A chest computed tomography (CT) scan demonstrated
      a large mass filling the entire left lung, associated with mediastinum and right
      lung compression and accompanied by destruction of the 2nd rib. The patient
      accepted chemotherapy and radiotherapy instead of a radical mass resection since
      the mass was irresectable. A good clinical response was achieved to the
      chemotherapy and radiotherapy. The diagnosis and treatment of Askin tumors
      remains a challenge for clinicians and surgeons due to the absence of standard
      therapeutic guidelines for the treatment of this disease. According to the
      experience obtained from the cases encountered to date, treatment strategies
      should aim to reduce local recurrence and distant metastasis. Moreover, surgery,
      chemotherapy and radiotherapy or a combination of these methods appears to
      constitute an effective treatment strategy for Askin tumors.

PMID- 24137452
TI  - U87MG glioma cells overexpressing IL-17 acclerate early-stage growth in vivo and
      cause a higher level of CD31 mRNA expression in tumor tissues.
AB  - Immunological alterations have been reported to be involved in glioma, the most
      common malignant disease of the adult brain. Our recent study identified higher
      levels of IL-17 in glioma specimens. The present study investigated the role and
      possible mechanisms of IL-17 in glioma tumorigenesis. Human IL-17 cDNA was cloned
      and inserted into the eukaryotic pEGFP-N1 expression vector, which was used to
      transfect the glioma U87MG cell line, resulting in a high level of IL-17
      expression in these cells. The cells were then transfected with IL-17 (pEGFP-N1
      IL-17-U87MG) or mock (pEGFP-N1-U87MG) vector or left untransfected (U87MG) and
      subcutaneously inoculated into the right flank of nude mice. The results revealed
      that the pEGFP-N1-IL-17-U87MG cells grew more rapidly in the early stages
      (P<0.05, determined on day 32 post-inoculation compared with the other two
      groups). Quantitative (q)PCR detected higher mouse (m)CD31 mRNA levels in the IL
      17-transfected group (P<0.01) compared with the mock-transfected and
      untransfected groups. IL-17 transfection altered the mRNA expression of a panel
      of molecules that are associated with immunity and inflammation in U87MG cells in
      vitro. An effect of the vector was identified, whereby the mock transfection
      strongly inhibited cell growth in vivo and dramatically altered the mRNA levels
      of multiple molecules in the cell culture in vitro compared with the
      untransfected cells. The present study confirmed that IL-17 overexpression may
      enhance glioma cell growth in vivo, which may be associated with accelerated
      angiogenesis. IL-17 overexpression may also alter the cellular mRNA expression of
      immune-related molecules.

PMID- 24137453
TI  - Jagged1 contributes to the drug resistance of Jurkat cells in contact with human
      umbilical cord-derived mesenchymal stem cells.
AB  - Notch signaling, which is driven by the Notch1 receptor, plays an essential role
      in the pathogenesis and stroma-mediated drug resistance of T-cell acute
      lymphoblastic leukemia (T-ALL). However, little is known about the roles of Notch
      ligands in the survival or drug resistance of T-ALL cells. In the present study,
      isolated mesenchymal stem cells (MSCs) from human umbilical cord (hUC) samples,
      termed hUC-MSCs, were used as stromal cells for the Jurkat T-ALL cell line. The
      role of the Notch ligand, Jagged1, was assessed in the survival of Jurkat T-ALL
      cells using this co-culture system. hUC-MSCs and Jurkat cells were observed to
      express Jagged1. Furthermore, co-culture with hUC-MSCs led to a significant
      upregulation of Jagged1 and a more significant overexpression of its receptor,
      Notch1, in the Jurkat cells, indicating that the receptor and ligand pair may
      play a role in the reciprocal or autonomous activation of the Notch pathway. In
      addition, a higher level of CD28 expression was observed in the Jurkat cells that
      were co-cultured with hUC-MSCs. Blocking Jagged1 expression using neutralizing
      antibodies restored drug-induced apoptosis in the Jurkat cells that were co
      cultured with hUC-MSCs, and also increased the drug sensitivity of the Jurkat
      cells that were cultured alone. By contrast, direct incubation with exogenously
      recombinant Jagged1 produced the same protective effects in Jurkat cells as those
      induced by hUC-MSCs. These results indicate a significant role for Jagged1 in hUC
      MSC-induced survival and the self-maintenance of the Jurkat T-ALL cell line,
      making it a potential target for the treatment of human T-ALL.

PMID- 24137454
TI  - Vertebroepidural metastasis of an ethmoid adenocarcinoma: A case report.
AB  - Ethmoid adenocarcinoma is the most frequent ethmoid tumor. To date, only a single
      case of spinal cord compression resulting from ethmoid adenocarcinoma has been
      reported. The current case study presents a recent case of vertebroepidural
      metastasis of an ethmoid adenocarcinoma leading to spinal cord compression.
      Modern imaging studies, including magnetic resonance imaging (MRI) and 18
      fludeoxyglucose positron emission tomography (FDG PET), as well as histological
      and immunohistochemical analyses, have led to diagnoses of a metastasis of an
      ethmoid adenocarcinoma, which is a mucinous variant, dedifferentiated when
      compared to the primary tumor. The present case discusses current diagnostic and
      treatment protocols of this condition. Since survival rates associated with the
      primary tumor are improving, the incidence of spinal metastasis of ethmoid
      carcinomas is likely to increase in the future, therefore requiring appropriate
      diagnostic and therapeutic management.

PMID- 24137455
TI  - Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal
      cancer: A single-center report.
AB  - In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor
      receptor (EGFR), was approved in Japan for clinical use against chemotherapy
      refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical
      Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC
      cases were administered immunohistochemistry with cetuximab as salvage
      monotherapy. The safety, side-effects and clinical efficacy of the treatment,
      including response rate, time to treatment failure, progression-free and overall
      survival, K-ras mutation status and impact on outcome, were investigated. The
      patient tumor growth control rate (TCR) was 38%, the mean time to progression
      (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2-12.4] and the mean overall
      survival (OS) was 49.4 weeks (95% CI, 30.1-68.8). The most common adverse
      reactions reported were skin reactions, including acne (67%), hand-foot syndrome
      (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia
      (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the
      present single-center study demonstrated that cetuximab monotherapy is beneficial
      for the treatment of chemotherapy-refractory patients with mCRC and that it has
      an acceptable level of safety and manageable side-effects.

PMID- 24137456
TI  - Post-operative urothelial recurrence in patients with upper urinary tract
      urothelial carcinoma managed by radical nephroureterectomy with an ipsilateral
      bladder cuff: Minimal prognostic impact in comparison with non-urothelial
      recurrence and other clinical indicators.
AB  - Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, and novel
      prognostic factors for patients who have undergone a radical nephroureterectomy
      (RNU) for UTUC have been studied intensely. To the best of our knowledge, the
      prognostic value of urothelial recurrence in patients with UTUC has not been
      previously described in studies. The present study compared the prognostic value
      of urothelial and non-urothelial recurrence in patients with UTUC of the kidney
      and ureter managed by surgery. The inclusion criteria consisted of a diagnosis of
      non-metastatic UTUC (any T stage, N0-1 and M0) and receipt of an RNU with an
      ipsilateral bladder cuff as the primary treatment. Of the 153 patients that were
      screened for the study, comprehensive clinical and pathological data was
      available for 103 patients, who were consequently included in the analysis.
      Overall survival (OS) and cancer-specific survival (CSS) times were estimated. A
      multivariate analysis was performed using the Cox regression model. The median
      follow-up period was 29 months (interquartile range, 14-63 months). The patient
      population was comprised of 71 males (68.9%) and 32 females (31.1%). A total of
      32 patients (31.1%) showed non-urothelial recurrence, while 38 patients (36.9%)
      exhibited urothelial recurrence and 33 patients (32.0%) exhibited no recurrence.
      When comparing the risk parameters between the non-urothelial recurrence
      categories, the factors of pathological grade, microvascular invasion, lymphatic
      invasion and pT classification showed significant differences. However, there
      were no significant differences between the urothelial recurrence categories. No
      significant difference was observed between the OS and CSS times within the
      urothelial recurrence categories (P=0.3955 and P=0.05891, respectively), but
      significant differences were identified in the non-urothelial recurrence
      categories (P<0.0001 and P<0.0001, respectively). Among the other relevant
      descriptive pre-operative characteristics in the multivariate analysis, only non
      urothelial recurrence remained associated with a worse CSS [P=0.002; hazard ratio
      (HR) 9.512]. The results show that urothelial recurrence has a minimal prognostic
      value in patients with UTUC managed by RNU with an ipsilateral bladder cuff.

PMID- 24137457
TI  - Glomus tumor of the shoulder: A case report and review of the literature.
AB  - Glomus tumors are benign neoplasms that arise from neuromyoarterial glomus
      bodies, with clinical manifestations that include acute pain, cold intolerance
      and tenderness. Glomus tumors may occur anywhere in the skin, soft tissue or
      gastrointestinal tract, but are most frequently encountered in the nail bed of
      the hands. The present study reports the case of a 30-year-old female with a
      history of shoulder pain caused by a cystic neoformation. Following surgery, a
      microscopic examination revealed nests of small cells of a rounded and regular
      shape. The tumor cells exhibited positive expression for CD34 and smooth muscle
      actin. This study supports and confirms the fact that a glomus tumor is a benign
      neoplasm that may occur in multiple locations. Therefore, the significance of a
      histological and immunohistochemical approach for a correct characterization of
      this lesion is required.

PMID- 24137458
TI  - miR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2.
AB  - MicroRNAs (miRNAs) have significant roles in cell processes, including
      proliferation, apoptosis and stress responses. To investigate the involvement of
      miR-99 in the inhibition of HeLa cell proliferation, an miR-99 gene expression
      vector (pU6.1/miR-99), which overexpressed miR-99 in HeLa cells after transient
      transfection, was constructed. The expression of miR-99 was detected by qPCR.
      Cell proliferation and apoptosis were analyzed by cell viability, proliferation
      and apoptosis assays, as well as by electron microscopy. The results showed that
      overexpression of miR-99 in HeLa cells increased the HeLa cell mortality rate.
      Moreover, miR-99 overexpression was able to markedly inhibit HeLa cell
      proliferation according to the 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The cell apoptosis rate was significantly
      higher in pU6.1/miR-99-treated cells compared with that in the control cultures.
      Increases in intracellular electron density, as well as the proportion of nuclear
      plasma, blebbing phenomena and apoptotic bodies were observed in pU6.1/miR-99
      treated cells compared with control cultures according to electron microscopy
      analysis. The Tribbles 2 (TRIB2) 3'-untranslated region was also observed to be
      targeted by miR-99 and the results further demonstrated that miR-99 was able to
      negatively regulate TRIB2 expression in HeLa cells The results indicate that miR
      99 acts as a tumor suppressor gene in HeLa cells, establishing a theoretical
      basis for its application in cancer therapeutics.

PMID- 24137459
TI  - Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced
      apoptosis in human nasopharyngeal carcinoma cells.
AB  - Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream treatments
      for nasopharyngeal carcinoma (NPC), which effectively improve the outcome and
      reduce tumor recurrence. However, the resistance mechanism(s) involved in
      radiotherapy and chemotherapy, which is the main barrier in NPC treatment,
      remains undefined. Therefore, there is an urgent requirement for the
      identification of new therapeutic strategies or adjuvant drugs. In the present
      study, the effects of autophagy inhibitors on endoplasmic reticulum (ER) stress
      induced autophagy was investigated. Combining 3-methyladenine (3-MA) with
      cisplatin (DDP), ionizing radiation (IR), 2-deoxy-D-glucose (2-DG) or tunicamycin
      (TM) resulted in enhanced cell death, as revealed by MTT and colony formation
      assays. Flow cytometry results demonstrated that the sensitivity of NPC cells to
      DDP- and IR-induced apoptosis was not significant. DDP, IR, 2-DG and TM induced
      ER stress and autophagy. Using fluorescence microscopy, 3-MA was identified to
      increase the apoptotic cell death induced by DDP, IR, 2-DG or TM. In addition, 3
      MA inhibited the increased autophagy induced by DDP, IR, 2-DG or TM, as
      demonstrated by western blot analysis and immunocytochemistry results. Results of
      the present study indicate that autophagy acts as a protective mechanism response
      to the apoptosis induced by DDP, IR, 2-DG or TM.

PMID- 24137460
TI  - A polysaccharide isolated from Agaricus blazei Murill (ABP-AW1) as a potential
      Th1 immunity-stimulating adjuvant.
AB  - In the present study, a low molecular weight polysaccharide, ABP-AW1, isolated
      from Agaricus blazei Murill was assessed for its potential adjuvant activity. ABP
      AW1 is considered to create a 'depot' of antigen at a subcutaneous injection
      site. ICR mice were immunized with 100 MUg ovalbumin (OVA) alone or with 100 MUg
      OVA formulated in 0.9% saline containing 200 MUg aluminum (alum) or ABP-AW1 (50,
      100 and 200 MUg) on days 1 and 15. Two weeks after the secondary immunization,
      splenocyte proliferation, the expression of surface markers, cytokine production
      and the OVA-specific antibody levels in the serum were determined. The OVA/ABP
      AW1 vaccine, in comparison with OVA alone, markedly increased the proliferation
      of splenic lymphocytes and elicited greater antigen-specific CD4+ T cell
      activation, as determined by splenic CD4+CD69+ T cells and Th1 cytokine
      interferon (IFN)-gamma release. The combination of ABP-AW1 and OVA also enhanced
      IgG2b antibody responses to OVA. In conclusion, these data indicated that ABP-AW1
      significantly enhanced the humoral and cellular immune responses against OVA in
      the mice, suggesting that ABP-AW1 stimulated Th1-type immunity. We suggest that
      ABP-AW1 may serve as a new adjuvant.

PMID- 24137461
TI  - PIAS3 promotes homology-directed repair and distal non-homologous end joining.
AB  - A DNA double-strand break (DSB) is the most severe form of DNA damage and is
      mainly repaired through homologous recombination (HR), which has a high fidelity,
      or non-homologous end joining (NHEJ), which is prone to errors. Defects in the
      DNA damage response lead to genomic instability and ultimately the predisposition
      of organs to cancer. Protein inhibitor of activated STAT-1 (PIAS1), which is a
      potential small ubiquitin-related modifier (SUMO) ligase, has been reported to be
      involved in DSB repair. The present study identified that another member of the
      PIAS family, PIAS3, is also an enhancer for HR- and NHEJ-mediated DSB repair.
      Furthermore, the overexpression of PIAS3 was demonstrated to increase the
      resistance of HeLa cells to ionizing radiation (IR), indicating a significant
      role for PIAS3 in the DNA damage response (DDR) pathway.

PMID- 24137462
TI  - Merkel cell polyomavirus and extrapulmonary small cell carcinoma.
AB  - The Merkel cell polyomavirus (MCV) is involved in the development of up to 100%
      of Merkel cell cancer (MCC) cases. Early studies have reported that the virus was
      infrequently detected in other small cell or neuroendocrine lung carcinomas,
      which share histological features with MCC. The present study investigated the
      presence of MCV in cases of extrapulmonary small cell carcinoma (ESCC), which
      also shares histological features with MCC. A total of 25 cases of ESCC that were
      diagnosed between 2004 and 2009 were identified at The Dartmouth Hitchcock
      Medical Center. Archived tissue was available for testing in 16 of these cases. A
      total of 11 tissue specimens of MCC were used as positive controls. DNA that was
      extracted from the archived tissue was subjected to five separate quantitative
      (q)PCR assays for the detection of four MCV genomic targets. MCV DNA was detected
      in 3/16 (19%) of the ESCCs and in all 11 MCCs. In the three MCV-positive ESCCs,
      the viral target was only detected by either one or two of the PCR assays. In
      8/11 MCV-positive MCCs, the DNA tested positive by either three or all four
      assays and the remaining three MCCs tested positive by either one or two assays.
      The beta-globin endogenous control was detected in all the samples that were
      tested. Although MCC and ESCC share numerous histological features, MCV is
      detected at a lower frequency in ESCC. The possible role for MCV in the etiology
      of ESCC remains uncertain and may account for the rare cases of ESCC with no
      other identifiable etiology. The failure of other assays to detect MCV may be due
      to sequence variability in the MCV genome.

PMID- 24137463
TI  - Early and late urodynamic assessment of the orthotopic N-shaped neobladder.
AB  - The present study aimed to report the urodynamic data from 46 male patients who
      underwent an orthotopic N-shaped neobladder replacement following a radical
      cystectomy during a 12-month period and to provide urodynamic evidence for the
      improvement of this technique. A total of 46 consecutive male patients underwent
      a radical cystectomy and orthotopic N-shaped neobladder substitution due to
      muscle-invasive bladder cancer. Uroflowmetry, cystometry and urethral pressure
      profilometry were analyzed at 3-12 months following the surgery. The mean
      pressure of the neobladders was <15 cm H2O at volumes of <400 ml and 22.4 cm H2O
      at 100% capacity at 6 months. The mean pressure of the contractions was <40 cm
      H2O at 6 months. The mean filling pressure following the surgery at 3 months was
      higher compared with that at 6 months. No difference was observed at the other
      time-points. When comparing the 9- and 12-month urodynamic characteristics, no
      significant changes were observed in the cystometric capacity. The mean post-void
      residual (PVR) urine volume was 58 ml. A mean voiding peak of 16.2 ml/sec was
      obtained using the Valsalva maneuver. The daytime continence rate was 90% at 12
      months while the night-time continence rate was 60%.

PMID- 24137464
TI  - Surgical outcome of laparoscopic colectomy for colorectal cancer in obese
      patients: A comparative study with open colectomy.
AB  - The aim of the present study was to assess the short-term outcome and survival
      time of 166 obese patients who received laparoscopic and open colectomy for
      colorectal cancer (CRC) between January 2007 and December 2012. All 166 patients
      included in the study had a BMI >28. Laparoscopic or open colectomy procedures
      were performed on 64 and 102 patients, respectively. The short-term outcome and
      post-operative survival rates were compared. The patient characteristics were
      similar between the two groups. Laparoscopic colectomy correlated with an
      increased duration of surgery compared with open colectomy (183 vs. 167 min,
      respectively; P<0.05) but intraoperative blood loss was decreased (168 vs. 188
      ml, respectively; P<0.05). Hospitalization costs were slightly higher following
      the laparoscopic procedure compared with open surgery, but this was affordable
      for the majority of patients (Y56,484 vs. Y56,161, respectively; P<0.05). The
      incidence of wound infection (17 vs. 31%; P<0.05) and abdominal abscess rates (6
      vs. 18%; P<0.05) were reduced in the laparoscopic group compared with the open
      group. Pathological characteristics were identified to be similar and no
      significant differences were identified in overall (log-rank test; P=0.85) and
      disease-free (log-rank test; P=0.85) survival between the two types of surgery
      (log-rank test; P=0.76). The current retrospective study demonstrated an improved
      short-term outcome in laparoscopic colectomy for CRC patients with a BMI >28
      compared with patients who underwent the open procedure. Laparoscopic colectomy
      is technically and oncologically safe and must be popularized in obese CRC
      patients.

PMID- 24137465
TI  - Sensitive methods for the detection of an insertion in exon 20 of the HER2 gene
      in the metastasis of non-small cell lung cancer to the central nervous system.
AB  - The HER2 (ErbB2/neu) protein is a member of the HER (ErbB) receptor family (EGFR,
      HER2, HER3 and HER4) that expresses tyrosine kinase activity in the intracellular
      domain. EGFR and HER2 overexpression is observed in numerous types of cancer,
      nevertheless, the susceptibility of patients with non-small cell lung cancer
      (NSCLC) to therapy with EGFR and HER2 tyrosine kinase inhibitors (TKIs) depends
      on mutations present in the respective coding genes (driver mutations). In the
      present study, PCR and amplified DNA fragment length analysis (FLA) were used
      along with the multi-temperature single-strand conformation polymorphism (MSSCP)
      technique in order to identify the 12 base pair insertion in exon 20 of the HER2
      gene in 143 patients with NSCLC metastasis to the central nervous system. The
      prevalence of the HER2 gene mutation was correlated with mutations in the EGFR
      and BRAF genes. The insertion in exon 20 of the HER2 gene was observed in a
      single 77-year-old, non-smoking male, with poorly-differentiated adenocarcinoma
      of the lung (1.5% of adenocarcinoma patients). No other genetic abnormalities
      were identified in this patient. In the therapy of NSCLC patients with HER2 gene
      mutations, drugs that inhibit the EGFR and HER2 receptors, for example afatinib,
      may be effective. The identification of other driving mutations in NSCLC cells
      appears to be key to the appropriate qualification of molecular targeted
      therapies.

PMID- 24137466
TI  - Vascular endothelial growth factor gene polymorphisms and renal cell carcinoma: A
      systematic review and meta-analysis.
AB  - Renal cell carcinoma (RCC) accounts for 3% of all cancer-related mortalities in
      adults. The risk factors for the development of RCC remain under investigation.
      Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and
      is crucial for the development and metastasis of tumors, including RCC. VEGF gene
      polymorphisms may alter VEGF protein concentrations, affect the process of
      angiogenesis and may be involved in inter-individual variation in carcinogenesis.
      In the present study, a systematic review and meta-analysis were performed based
      on published case-control studies in order to estimate the association between
      VEGF gene polymorphisms and the susceptibility to RCC. A total of five studies
      that involved eight polymorphisms and were published between January 2000 and
      December 2012 were identified from PubMed. The results of this systematic review
      and meta-analysis indicate that the VEGF 936C/T, 1612G/A, -1154G/A, -2549I/D, 
      460T/C and 405G/C gene polymorphisms are not associated with the risk of RCC.
      There was no polymorphism in 702C/T and RCC and the -2578C/A gene polymorphism
      may be associated with an increased risk of RCC. However, due to the limitations
      of the present study, further high quality case-control studies are warranted to
      confirm these findings.

PMID- 24137467
TI  - Correlation between the EGF gene intronic polymorphism, rs2298979, and colorectal
      cancer.
AB  - Colorectal cancer (CRC) is an important disorder that results from genetic and
      epigenetic alterations in one colonic epithelial cell. Epidermal growth factor
      (EGF) is critical in the development of tumors in epithelial tissues. Variations
      in the DNA sequence of the EGF gene may be particularly significant with regard
      to susceptibility to CRC. The present study aimed to investigate the effect of
      the EGF gene single nucleotide polymorphism (SNP), rs2298979, on CRC. In this
      prospective study, 220 samples were collected from patients with CRC and compared
      with 220 matched healthy controls. Genotyping was performed using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and
      the result was validated by direct sequencing. A significant correlation was
      observed between the rs2298979 variant in the EGF gene and CRC. The frequency of
      the A/G genotype in the control group was higher than in the patients with
      sporadic CRC [odds ratio (OR), 0.488; 95% confidence interval (CI), 0.307-0.774;
      P=0.002]. In this study there were no individuals with a G/G genotype. Although
      the frequency of the G and A alleles was similar in the healthy control and CRC
      patient groups, individuals with the A/G genotype were less susceptible to CRC
      compared with those with the A/A genotype.

PMID- 24137468
TI  - Triptolide avoids cisplatin resistance and induces apoptosis via the reactive
      oxygen species/nuclear factor-kappaB pathway in SKOV3PT platinum-resistant human
      ovarian cancer cells.
AB  - An acquired resistance to platinum-based drugs has emerged as a significant
      impediment to effective ovarian cancer therapy. The present study explored the
      anticancer mechanisms of triptolide (TPL) in SKOV3PT platinum-resistant human
      ovarian cancer cells and observed that TPL activated caspase 3 and induced the
      dose-dependent apoptosis of the SKOV3PT cells. Furthermore, TPL inhibited complex
      I of the mitochondrial respiratory chain (MRC) followed by an increase of
      reactive oxygen species (ROS), which further inhibited nuclear factor (NF)-kappaB
      activation and resulted in the downregulation of anti-apoptotic proteins, Bcl-2
      and X-linked inhibitor of apoptosis protein (XIAP). Notably, the pre-treatment
      with N-acetyl-L-cysteine (NAC) abolished the TPL-induced ROS generation, NF
      kappaB inhibition and cell apoptosis, but did not affect the inhibitory effect of
      TPL on complex I activity. These results suggested that TPL negatively regulated
      the NF-kappaB pathway through mitochondria-derived ROS accumulation, promoting
      the apoptosis of the SKOV3PT cells. Furthermore, TPL synergistically enhanced the
      cytotoxicity of cisplatin against platinum-resistant ovarian cancer cells.
      Collectively, these findings suggest that TPL is able to overcome chemoresistance
      and that it may be an effective treatment for platinum-resistant ovarian cancer,
      either alone or as an adjuvant therapy.

PMID- 24137469
TI  - Inhibition of nm23-H1 gene expression in chronic myelogenous leukemia cells.
AB  - For solid tumors of a malignant origin, the expression of the nm23-H1 gene is a
      positive prognostic factor. However, for chronic myeloid leukemia (CML), the
      prognostic role of nm23-H1 gene expression is unknown. The present study
      investigated the impact of nm23-H1 gene expression on the proliferation and
      migration of the CML K562 cell line to elucidate the association between nm23-H1
      gene expression and CML cell survival. An RNAi lipo-recombinant plasmid of the
      nm23-H1 gene (pGCsi-nm23-H1) was constructed and transfected into the K562 cells.
      RT-PCR and western blotting were used to detect nm23-H1 mRNA and protein
      expression, respectively. The anchorage-independent growth ability of the
      transfected cells was observed in soft agar culture and the ability of the K562
      cells to migrate was determined using a Transwell assay. Following the successful
      construction and transfection of the pGCsi-nm23-H1 plasmid into the K562 cells,
      nm23-H1 mRNA and protein expression levels were significantly lower compared with
      the control group. The stably-transfected pGCsi-nm23-H1 K562 cells exhibited a
      markedly increased ability to form colonies and the number and sizes of the
      colonies were significantly increased compared with those of the control. In
      vitro, the cells migrated through a Matrigel-coated membrane during incubation
      for 20 h. The Transwell assay revealed that the quantitative number of pGCsi-nm23
      H1 K562 cells that migrated into the lower compartment of the invasion chamber
      was markedly increased compared with the control. In conclusion, nm23-H1 gene
      expression may inhibit K562 cell proliferation and migration. nm23-H1 may be a
      cancer suppressor gene and play a significant role in inhibiting the survival of
      CML cells.

PMID- 24137470
TI  - Decreased copy number of mitochondrial DNA: A potential diagnostic criterion for
      gastric cancer.
AB  - An alteration in the mitochondrial DNA (mtDNA) copy number has been detected in
      numerous human cancers. However, certain changes in the mtDNA copy number that
      occur during the initiation and progression of gastric cancer remain undetected.
      In the present study, using quantitative PCR analysis, the quantitative changes
      in mtDNA were observed during the initiation and progression of gastric cancer.
      Furthermore, the possible correlation between the changes in mtDNA and the
      clinicopathological stage were also investigated. However, the mechanism by which
      the change in mtDNA copy number occurs remains to be elucidated. Epigenetic
      changes are believed to play a significant role in regulating the mtDNA content.
      In order to determine whether there is a potential correlation between DNA
      methylation and mtDNA regulation, in vitro demethylation experiments were
      performed. Tumor tissues and corresponding non-cancerous tissues were surgically
      resected from 76 gastric cancer patients between 2010 and 2011. The results
      revealed that the average relative mtDNA copy numbers were 94.71+/-28.11 in the
      cancer tissues and 111.68+/-21.84 in the corresponding non-cancerous tissues
      (P<0.01). The quantitative changes in mtDNA demonstrated a significant decrease
      in gastric cancer, particularly in ill-defined stage III and IV cases, but had no
      association with gender. The mtDNA copy numbers demonstrated a marked increase
      (P<0.05) following demethylation treatment. The present results indicate that the
      mtDNA copy number plays a significant role during the progression of colorectal
      cancer, particularly during the late clinicopathological stages, and that the
      change in the mtDNA copy number may correlate with DNA methylation.

PMID- 24137471
TI  - Outcomes for patients who are diagnosed with breast and endometrial cancer.
AB  - The present study sought to determine the survival outcomes for women diagnosed
      with breast and endometrial cancer. Using SEER data, a population-based cohort
      study of women diagnosed with breast and endometrial cancer was conducted. Kaplan
      Meier survival curves were created for disease-specific survival rates. A total
      of 2,027 women diagnosed with breast and endometrial cancer were identified. Of
      these, 1,296 (63.9%) developed breast cancer first and 731 (36.1%) developed
      endometrial cancer first. Regional lymph node involvement was significantly more
      common with a breast cancer diagnosis [522 (25.8%) women] compared with an
      endometrial cancer diagnosis [87 (4.3%) women] (P<0.05). Factors associated with
      decreased survival included a high tumor grade in endometrial cancer, nodal
      positivity and estrogen receptor-negative breast cancer (P<0.05 for each). There
      were 83 (4.1%) mortalities due to breast cancer, 63 (3.1%) mortalities due to
      endometrial cancer and 178 (8.8%) mortalities due to other causes (P<0.05). In
      conclusion, for women diagnosed with breast and endometrial cancer, the
      cumulative risk of mortality at five years following the second cancer diagnosis
      is nearly four times more likely to be due to breast cancer than endometrial
      cancer.

PMID- 24137472
TI  - Isolated solitary brain metastasis as a relapse of small cell lung cancer.
AB  - The brain is one of the most common sites for the metastasis of small cell lung
      cancer (SCLC). The present study describes two cases of an isolated solitary
      brain metastasis as a relapse of SCLC, which occurred more than one year after
      the completion of the initial successful treatment for SCLC. The tumors were
      identified during a regular check-up computed tomography (CT) scan and were
      successfully treated. To the best of our knowledge, this is the first study to
      report the cases of two patients with an isolated solitary brain metastasis as a
      relapse of SCLC. Although extremely rare, the possibility of such recurrences
      should be considered, particularly in patients who have refused prophylactic
      cranial irradiation.

PMID- 24137473
TI  - Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic
      therapy of human esophageal squamous cancer cells.
AB  - The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro
      pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell
      survival and in vivo tumor growth derived from human esophageal squamous cancer
      cells (Eca109). A cell counting kit 8 (CCK8) assay was used to assess the
      phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of
      tumor growth was determined by the changes in the relative tumor volume (RTV) and
      tumor weight. The results revealed that HPPH, in the range of 0.005-1 MUg/ml,
      exhibited no cytotoxicity in the Eca109 cells without light exposure and that the
      in vitro efficiency of HPPH-mediated PDT was higher compared with that of
      Photofrin(r)-mediated PDT. The in vivo results indicated that graded doses of
      HPPH-mediated PDT significantly inhibited the xenograft tumor growth derived from
      the Eca109 cells in a dose-dependent manner. The inhibition efficacy of 0.6 and
      1.0 mg/kg HPPH-mediated PDT was similar to that of 10 mg/kg Photofrin-mediated
      PDT. Furthermore, HPPH possessed a lower toxicity than Photofrin at the dose that
      achieved the same efficacy in mice bearing Eca109 subcutaneous tumors. The
      histopathological findings indicated that the tumor tissues in the
      photosensitizer (PS)-treated mice demonstrated varying degrees of necrosis. HPPH
      and Photofrin exhibited vascular cytotoxicity on the treated tumors. In
      conclusion, the present study demonstrated that the phototoxicity of HPPH
      mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH
      possessed lower toxicity than Photofrin at the dose that achieved the same
      efficacy. Therefore, HPPH may be a promising agent for treating human esophageal
      squamous cell cancer (ESCC).

PMID- 24137474
TI  - An aggressive form of non-Hodgkin's lymphoma with pleural and abdominal chylous
      effusions: A case report and review of the literature.
AB  - Serous effusions, including pleural, abdominal and pericardial effusions, are
      complications of lymphoma. Among these types, pleural effusions are the most
      common to be observed. However, the involvement of the abdominal or pericardial
      cavity is rare. An impairment of the lymphatic drainage and direct infiltration
      have been identified to play significant roles in effusion formation. Multiple
      techniques, including cytological exams, immunochemistry and cytogenetics, have
      been applied in the clinic to access the qualities of the effusions and to attain
      a fast and precise diagnosis. Serous effusions are associated with a poor outcome
      for patients with lymphoma. The present study describes the case of a 28-year-old
      male patient with aggressive non-Hodgkin's lymphoma (NHL) involving pleural and
      abdominal chylous effusions.

PMID- 24137475
TI  - Spica Prunellae extract inhibits the proliferation of human colon carcinoma cells
      via the regulation of the cell cycle.
AB  - Spica Prunellae has long been used as a significant component in numerous
      traditional Chinese medicine (TCM) formulas to clinically treat cancers.
      Previously, Spica Prunellae was shown to promote cancer cell apoptosis and
      inhibit angiogenesis in vivo and in vitro. To further elucidate the precise
      mechanism of its tumoricidal activity, the effect of the ethanol extract of Spica
      Prunellae (EESP) on the proliferation of human colon carcinoma HT-29 cells was
      elucidated and the underlying molecular mechanisms were investigated. The
      proliferation of HT-29 cells was evaluated using 3-(4, 5-dimethyl-thiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) and colony formation analyses. The cell
      cycle was determined using fluorescence-activated cell sorting (FACS) with
      propidium iodide (PI) staining. The mRNA and protein expression of cyclin
      dependent kinase 4 (CDK4) and cyclin D1 was examined using RT-PCR and western
      blotting, respectively. EESP was observed to inhibit HT-29 viability and survival
      in a dose- and time-dependent manner. Furthermore, EESP treatment blocked G1/S
      cell cycle progression and reduced the expression of pro-proliferative cyclin D1
      and CDK4 at the transcriptional and translational levels. Altogether, these data
      suggest that the inhibition of cell proliferation via G1/S cell cycle arrest may
      be one of the mechanisms through which Spica Prunellae treats cancer.

PMID- 24137476
TI  - Serum follicle-stimulating hormone level is associated with human epidermal
      growth factor receptor type 2 and Ki67 expression in post-menopausal females with
      breast cancer.
AB  - The present study aimed to determine the association between levels of the gender
      hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      progesterone (P) and prolactin (PRL), and two breast cancer molecular markers,
      human epidermal growth factor receptor 2 (Her-2) and Ki67, in post-menopausal
      patients with breast cancer. A retrospective study of the serum hormone levels of
      FSH, LH, P and PRL and the expression status of Her-2 and Ki67 was performed
      using 187 post-menopausal females with breast cancer. Her-2+ breast cancer
      patients exhibited higher serum FSH levels compared with Her-2- patients (69.47+/
      3.219 vs. 58.56+/-1.516 IU/l). The patients with high Ki67 expression
      [immunohistochemistry (IHC), 3+] displayed higher FSH (72.51+/-4.616 vs. 60.53+/
      1.476 IU/l) and LH (32.33+/-1.916 vs. 26.98+/-0.8852 IU/l) levels than those with
      lower Ki67 expression. No correlation was identified between the FSH, LH, P and
      PRL hormone levels, tumor stages and lymphovascular invasion (LVI). In
      conclusion, a higher serum FSH level was identified in Her-2+ post-menopausal
      patients with breast cancer. Higher serum FSH and LH levels were also observed in
      breast cancer patients with high Ki67 expression. FSH and LH may function in the
      progression of breast cancer.

PMID- 24137477
TI  - microRNA and gene networks in human pancreatic cancer.
AB  - To date, scientists have obtained a substantial amount of knowledge with regard
      to genes and microRNAs (miRNAs) in pancreatic cancer (PC). However, deciphering
      the regulatory mechanism of these genes and miRNAs remains difficult. In the
      present study, three regulatory networks consisting of a differentially-expressed
      network, a related network and a global network, were constructed in order to
      identify the mechanisms and certain key miRNA and gene pathways in PC. The
      interactions between transcription factors (TFs) and miRNAs, miRNAs and target
      genes and an miRNA and its host gene were investigated. The present study
      compared and analyzed the similarities and differences between the three networks
      in order to distinguish the key pathways. Certain pathways involving the
      differentially-expressed genes and miRNAs demonstrated specific features. TP53
      and hsa-miR-125b were observed to form a self-adaptation association. A further
      16 significant differentially-expressed miRNAs were obtained and it was observed
      that an miRNA and its host gene exhibit specific features in PC, for example, hsa
      miR-196a-1 and its host gene, HOXB7, form a self-adaptation association. The
      differentially-expressed network partially illuminated the mechanism of PC. The
      present study provides comprehensive data that is associated with PC and may aid
      future studies in obtaining pertinent data results with regards to PC. In the
      future, an improved understanding of PC may be obtained through an increased
      knowledge of the occurrence, mechanism, improvement, metastasis and treatment of
      the disease.

PMID- 24137478
TI  - Composition and potential anticancer activities of essential oils obtained from
      myrrh and frankincense.
AB  - The present study aimed to investigate the composition and potential anticancer
      activities of essential oils obtained from two species, myrrh and frankincense,
      by hydrodistillation. Using gas chromatography-mass spectrometry (GC-MS), 76 and
      99 components were identified in the myrrh and frankincense essential oils,
      respectively, with the most abundant components, 2-Cyclohexen-1-one, 4-ethynyl-4
      hydroxy-3,5,5-trimethyl- and n-Octylacetate, accounting for 12.01 and 34.66%,
      respectively. The effects of the two essential oils, independently and as a
      mixture, on five tumor cell lines, MCF-7, HS-1, HepG2, HeLa and A549, were
      investigated using the MTT assay. The results indicated that the MCF-7 and HS-1
      cell lines showed increased sensitivity to the myrrh and frankincense essential
      oils compared with the remaining cell lines. In addition, the anticancer effects
      of myrrh were markedly increased compared with those of frankincense, however, no
      significant synergistic effects were identified. The flow cytometry results
      indicated that apoptosis may be a major contributor to the biological efficacy of
      MCF-7 cells.

PMID- 24137479
TI  - Extracapsular wide resection of a femoral neck osteosarcoma and its
      reconstruction using a pasteurized autograft-prosthesis composite: A case report.
AB  - The requirement for an extracapsular resection is indicated for malignant bone
      tumors that have disseminated intracapsularly. Extracapsular resections are often
      performed for malignant tumors arising from the knee joint, but there are
      relatively few studies that have described an extracapsular resection of a tumor
      arising from the hip joint. The present study describes a case of extracapsular
      wide resection of the hip joint using rotational acetabular osteotomy. The
      patient was a 17-year-old female and the diagnosis was an osteoblastic
      osteosarcoma with a pathological fracture of the femoral neck. The joint was
      reconstructed using an allograft-implant composite graft and total hip
      arthroplasty. Although the patient presented a slight Trendelenburg gait, no
      recurrence or metastases were identified during a follow-up period of 3 years.
      The clinical features and surgical procedure of the case are described.

PMID- 24137480
TI  - Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular
      carcinoma.
AB  - Golgi protein 73 (GP73) is a resident Golgi type II transmembrane protein that
      has been reported to markedly increase in chronic liver disease, particularly in
      hepatocellular carcinoma (HCC). However, it remains unclear as to whether serum
      GP73 represents a reliable serum marker for the diagnosis of HCC. The aim of the
      present study was to evaluate the diagnostic value of serum GP73 in patients with
      HCC and to determine the diagnostic accuracy of measuring serum GP73 in
      combination with alpha-fetoprotein (AFP) and gamma-glutamyl transferase isoenzyme
      II (GGT-II) in HCC. Serum GP73 was detected using a time-resolved fluorescence
      immunological assay (TRFIA) and enzyme-linked immunosorbent assay (ELISA) in 79
      HCC cases, including 16 liver cirrhosis, 30 chronic hepatitis and 28 healthy
      individuals. The correlation between serum GP73 and tumor size and HCC grading
      was analyzed and the complementary diagnostic value of serum GP73, AFP and GGT-II
      was evaluated. TRFIA was established for the detection of serum GP73 and was
      sensitive and reproducible. The expression levels of serum GP73 were markedly
      higher in the patients with HCC when compared with those of the individuals with
      liver cirrhosis and chronic hepatitis or the healthy individuals. According to
      the receiver operating characteristic (ROC) curve, diagnostic sensitivity and
      specificity for HCC with a cut-off value of 78.1 ng/l were 73.4 and 79.0%,
      respectively. However, no correlation was identified among serum GP73 and tumor
      size or grading, and no correlations were identified among serum GP73, AFP and
      GGT-II. The diagnostic sensitivities for HCC, as detected by TRFIA of GP73, AFP
      and GGT-II, were 73.4, 55.6 and 68.4%, respectively, and the specificities were
      80.0, 86.7 and 97.1%, respectively. The combined determination of these markers
      increased the diagnostic sensitivity to 96.3% for HCC. TRFIA functions as a
      sensitive and replicable assay for the detection of serum GP73. The levels of
      serum GP73 were significantly higher in the HCC group when compared with the
      individuals with benign liver diseases. Serum GP73 may serve as a potential
      independent diagnostic candidate for HCC and the combined determination of serum
      GP73, AFP and GGT-II may increase the diagnostic efficiency of HCC.

PMID- 24137496
TI  - Do power lines and protected areas present a catch-22 situation for Cape vultures
      (Gyps coprotheres)?
AB  - Cape vulture Gyps coprotheres populations have declined across their range due to
      multiple anthropogenic threats. Their susceptibility to fatal collisions with the
      expanding power line network and the prevalence of carcasses contaminated with
      illegal poisons and other threats outside protected areas are thought to be the
      primary drivers of declines in southern Africa. We used GPS-GSM units to track
      the movements and delineate the home ranges of five adult (mean +/-SD minimum
      convex polygon area = 121,655+/-90,845 km(2)) and four immature (mean +/-SD
      minimum convex polygon area = 492,300+/-259,427 km(2)) Cape vultures to
      investigate the influence of power lines and their use of protected areas. The
      vultures travelled more than 1,000 km from the capture site and collectively
      entered five different countries in southern Africa. Their movement patterns and
      core foraging ranges were closely associated with the spatial distribution of
      transmission power lines and we present evidence that the construction of power
      lines has allowed the species to extend its range to areas previously devoid of
      suitable perches. The distribution of locations of known Cape vulture mortalities
      caused by interactions with power lines corresponded to the core ranges of the
      tracked vultures. Although some of the vultures regularly roosted at breeding
      colonies located inside protected areas the majority of foraging activity took
      place on unprotected farmland. Their ability to travel vast distances very
      quickly and the high proportion of time they spend in the vicinity of power lines
      and outside protected areas make Cape vultures especially vulnerable to negative
      interactions with the expanding power line network and the full range of threats
      across the region. Co-ordinated cross-border conservation strategies beyond the
      protected area network will therefore be necessary to ensure the future survival
      of threatened vultures in Africa.

PMID- 24137497
TI  - Effectiveness of HIV risk reduction interventions among men who have sex with men
      in China: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of risk reduction interventions on HIV
      knowledge, attitudes and behaviors among men who have sex with men (MSM) in
      China. METHODS: We performed a systematic review and meta-analysis of HIV risk
      reduction intervention studies among Chinese MSM. The summary difference of
      standardized mean differences (SMD) between both study arms or between pre- and
      post-intervention assessments were defined as the effect size (ES); ES was
      calculated using standard meta-analysis in random effects models. RESULTS: Thirty
      four eligible studies were included in the analysis, including two randomized
      clinical trials (RCT), six quasi-experimental studies, six pre-and-post
      intervention studies, and twenty serial cross-sectional intervention studies.
      These studies showed an increase in consistent condom use with any male sexual
      partners (mean ES, 0.46; 95% confidence interval [CI], 0.35-0.56), with regular
      sexual partners (mean ES, 0.41; 95% CI, 0.18-0.63), and casual sexual partners
      (mean ES, 0.52; 95% CI, 0.24-0.79). The analysis of ten studies that measured the
      impact on uptake of HIV testing also showed a positive result (mean ES, 0.55; 95%
      CI, 0.38-0.71). The risk reduction interventions also improved HIV/AIDS-related
      knowledge (mean ES, 0.77; 95% CI, 0.60-0.94) and attitudes (mean ES, 1.35; 95%
      CI, 0.91-1.79), but did not reduce prevalence of HIV (mean ES, 0.23; 95% CI, 0.02
      0.45) and syphilis infections (mean ES, -0.01; 95% CI, -0.19-0.17). There was
      significant heterogeneity among these studies. CONCLUSIONS: On aggregate, HIV
      risk reduction interventions were effective in reducing risky behaviors and
      improving knowledge and attitudes among Chinese MSM, but were not associated with
      a change in the prevalence of HIV and syphilis. Future studies should use
      incidence as definitive study outcome.

PMID- 24137498
TI  - Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its
      ability to inhibit the IP3 receptor.
AB  - The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2
      protein family. It has recently been demonstrated that Bcl-2, apart from its anti
      apoptotic role at mitochondrial membranes, can also directly interact with the
      inositol 1,4,5-trisphosphate receptor (IP3R), the primary Ca(2+)-release channel
      in the endoplasmic reticulum (ER). Bcl-2 can thereby reduce pro-apoptotic IP3R
      mediated Ca(2+) release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2
      BH4) has been identified as essential and sufficient for this IP3R-mediated anti
      apoptotic activity. In the present study, we investigated whether the reported
      inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the
      distinctive alpha-helical conformation of the BH4 domain peptide. We therefore
      designed a peptide with two glycine "hinges" replacing residues I14 and V15, of
      the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG). By comparing the structural and
      functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart,
      we found that the variant contained reduced alpha-helicity, neither bound nor
      inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar
      results were obtained with other substitutions in Bcl-2-BH4 that destabilized the
      alpha-helix with concomitant loss of IP3R inhibition. These results provide new
      insights for the further development of Bcl-2-BH4-derived peptides as specific
      inhibitors of the IP3R with significant pharmacological implications. 

PMID- 24137499
TI  - Subcutaneous interferon beta-1a may protect against cognitive impairment in
      patients with relapsing-remitting multiple sclerosis: 5-year follow-up of the
      COGIMUS study.
AB  - OBJECTIVE: To assess the effects of subcutaneous (sc) interferon (IFN) -1a on
      cognition over 5 years in mildly disabled patients with relapsing-remitting
      multiple sclerosis (RRMS). METHODS: Patients aged 18-50 years with RRMS (Expanded
      Disability Status Scale score <=4.0) who had completed the 3-year COGIMUS study
      underwent standardized magnetic resonance imaging, neurological examination, and
      neuropsychological testing at years 4 and 5. Predictors of cognitive impairment
      at year 5 were identified using multivariate analysis. RESULTS: Of 331 patients
      who completed the 3-year COGIMUS study, 265 participated in the 2-year extension
      study, 201 of whom (75.8%; sc IFN beta-1a three times weekly: 44 ug, n = 108; 22
      ug, n = 93) completed 5 years' follow-up. The proportion of patients with
      cognitive impairment in the study population overall remained stable between
      baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive
      impairment also remained stable in both treatment groups between baseline and
      year 5, and between year 3 and year 5. However, a significantly higher proportion
      of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046).
      Treatment with the 22 versus 44 ug dose was predictive of cognitive impairment at
      year 5 (hazard ratio 0.68; 95% confidence interval 0.48-0.97). CONCLUSIONS: This
      study suggests that sc IFN beta-1a dose-dependently stabilizes or delays
      cognitive impairment over a 5-year period in most patients with mild RRMS. Women
      seem to be more protected against developing cognitive impairment, which may
      indicate greater response to therapy or the inherently better prognosis
      associated with female sex in MS.

PMID- 24137522
TI  - Obstructive jaundice due to a rare periampullary tumor.
AB  - Gangliocytic paraganglioma is a rare neuroendocrine tumor predominantly arising
      in the second part of the duodenum with rare local recurrence or metastasis to
      regional lymph nodes. A 92-year-old female presented with obstructive jaundice.
      On exam she had pale conjunctiva and icteric sclera. Abdominal examination
      revealed tenderness in the upper abdomen. Laboratory data was consistent with
      obstructive jaundice. Computed tomography of the abdomen revealed a dilated gall
      bladder and a common bile duct (CBD) with no evidence of liver lesions or
      pancreatic head mass. Endoscopic ultrasonography revealed a 1 cm isoechoic
      submucosal nodule at the periampullary area, dilated CBD (9 mm), a prominent
      pancreatic duct (4.1 mm) and a hydropic gall bladder with no stones. Endoscopic
      retrograde cholangiopancreaticography was performed to relieve obstruction and
      showed a 1 cm periampullary mass which underwent an en-bloc snare resection.
      Histopathology analyses with immunohistochemical stains were positive for
      cytokeratin, synaptophysin, S-100 protein, neuron specific enolase and negative
      for actin and desmin consistent with periampullary gangliocytic paraganglioma.
      Periampullary gangliocytic paraganglioma is a rare benign tumor of the small
      bowel. Common presentation includes abdominal pain and obstructive jaundice which
      should be included in differential diagnosis of obstructive jaundice. Endoscopic
      resection is a curative therapy in the absence of local invasion or distant
      metastasis. 

PMID- 24137500
TI  - Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA
      synthesis and nuclear export of viral ribonucleoprotein complex upon influenza
      virus infection.
AB  - Influenza continues to pose a threat to humans by causing significant morbidity
      and mortality. Thus, it is imperative to investigate mechanisms by which
      influenza virus manipulates the function of host factors and cellular signal
      pathways. In this study, we demonstrate that influenza virus increases the
      expression and activation of sphingosine kinase (SK) 1, which in turn regulates
      diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF
      kappaB activation and markedly reduced the synthesis of viral RNAs and proteins.
      Further, SK blockade interfered with activation of Ran-binding protein 3
      (RanBP3), a cofactor of chromosome region maintenance 1 (CRM1), to inhibit CRM1
      mediated nuclear export of the influenza viral ribonucleoprotein complex. In
      support of this observation, SK inhibition altered the phosphorylation of ERK,
      p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation.
      Collectively, these results indicate that SK is a key pro-viral factor regulating
      multiple cellular signal pathways triggered by influenza virus infection. 

PMID- 24137523
TI  - Colonic tumour precipitating caecal volvulus within a diaphragmatic hernia.
AB  - An 85-year-old woman presented with sudden onset of generalised abdominal pain
      and absolute constipation for 4 d. On examination she had a distended abdomen.
      Plain abdominal radiograph revealed a gas filled viscous within the left upper
      quadrant. Subsequent computed tomography suggested caecal volvulus herniated
      through a left diaphragmatic hernia. The patient underwent reduction of the
      internal hernia, right hemicolectomy and mesh repair of the diaphragmatic hernia.
      Postoperative recovery was uneventful. Histology revealed a Dukes' A colonic
      cancer within the caecum. Herniation of caecal volvulus through a diaphragmatic
      hernia is a very rare condition and may have been precipitated by the colonic
      tumour. 

PMID- 24137524
TI  - Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam
      veterans.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between Agent
      Orange exposure and self-reported diseases in Korean Vietnam veterans. METHODS: A
      postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure
      to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent
      Orange exposure indices were constructed using division/brigade-level and
      battalion/company-level unit information. Adjusted odds ratios (ORs) for age and
      other confounders were calculated using a logistic regression model. RESULTS: The
      prevalence of all self-reported diseases showed monotonically increasing trends
      as the levels of perceived self-reported exposure increased. The ORs for colon
      cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral
      vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR,
      1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin
      diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were
      significantly elevated for the high exposure group in the division/brigade-level
      proximity-based exposure analysis, compared to the low exposure group. The ORs
      for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve
      palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and
      lipidemia (OR, 1.05) were significantly elevated for the high exposure group in
      the battalion/company-level analysis. CONCLUSIONS: Korean Vietnam veterans with
      high exposure to Agent Orange experienced a higher prevalence of several self
      reported chronic diseases compared to those with low exposure by proximity-based
      exposure assessment. The strong positive associations between perceived self
      reported exposure and all self-reported diseases should be evaluated with
      discretion because the likelihood of reporting diseases was directly related to
      the perceived intensity of Agent Orange exposure.

PMID- 24137526
TI  - Has income-related inequity in health care utilization and expenditures been
      improved? Evidence from the Korean National Health and Nutrition Examination
      Survey of 2005 and 2010.
AB  - OBJECTIVES: The purpose of this study is to examine and explain the extent of
      income-related inequity in health care utilization and expenditures to compare
      the extent in 2005 and 2010 in Korea. METHODS: We employed the concentration
      indices and the horizontal inequity index proposed by Wagstaff and van Doorslaer
      based on one- and two-part models. This study was conducted using data from the
      2005 and 2010 Korean National Health and Nutrition Examination Survey. We
      examined health care utilization and expenditures for different types of health
      care providers, including health centers, physician clinics, hospitals, general
      hospitals, dental care, and licensed traditional medical practitioners. RESULTS:
      The results show the equitable distribution of overall health care utilization
      with pro-poor tendencies and modest pro-rich inequity in the amount of medical
      expenditures in 2010. For the decomposition analysis, non-need variables such as
      income, education, private insurance, and occupational status have contributed
      considerably to pro-rich inequality in health care over the period between 2005
      and 2010. CONCLUSIONS: We found that health care utilization in Korea in 2010 was
      fairly equitable, but the poor still have some barriers to accessing primary care
      and continuing to receive medical care.

PMID- 24137525
TI  - Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels and their association with age,
      body mass index, smoking, military record-based variables, and estimated exposure
      to Agent Orange in Korean Vietnam veterans.
AB  - OBJECTIVES: The aim of this study was to examine the levels of serum 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and evaluate their association with age, body
      mass index, smoking, military record-based variables, and estimated exposure to
      Agent Orange in Korean Vietnam veterans. METHODS: Serum levels of TCDD were
      analyzed in 102 Vietnam veterans. Information on age, body mass index, and
      smoking status were obtained from a self-reported questionnaire. The perceived
      exposure was assessed by a 6-item questionnaire. Two proximity-based exposures
      were constructed by division/brigade level and battalion/company level unit
      information using the Stellman exposure opportunity index model. RESULTS: The
      mean and median of serum TCDD levels was 1.2 parts per trillion (ppt) and 0.9
      ppt, respectively. Only 2 Vietnam veterans had elevated levels of TCDD (>10 ppt).
      The levels of TCDD did not tend to increase with the likelihood of exposure to
      Agent Orange, as estimated from either proximity-based exposure or perceived self
      reported exposure. The serum TCDD levels were not significantly different
      according to military unit, year of first deployment, duration of deployment,
      military rank, age, body mass index, and smoking status. CONCLUSIONS: The average
      serum TCDD levels in the Korean Vietnam veterans were lower than those reported
      for other occupationally or environmentally exposed groups and US Vietnam
      veterans, and their use as an objective marker of Agent Orange exposure may have
      some limitations. The unit of deployment, duration of deployment, year of first
      deployment, military rank, perceived self-reported exposure, and proximity-based
      exposure to Agent Orange were not associated with TCDD levels in Korean Vietnam
      veterans. Age, body mass index and smoking also were not associated with TCDD
      levels.

PMID- 24137527
TI  - Differences in cigarette use behaviors by age at the time of diagnosis with
      diabetes from young adulthood to adulthood: results from the National
      Longitudinal Study of Adolescent Health.
AB  - OBJECTIVES: Previous observations propose that risk-taking behaviors such as
      cigarette smoking are prevailing among young people with chronic conditions
      including diabetes. The purpose of this study was to examine whether cigarette
      smoking is more prevalent among diabetics than non-diabetics and whether it
      differs by age at the time of diagnosis with diabetes from young adulthood (YAH)
      to adulthood (AH). METHODS: We used US panel data from the National Longitudinal
      Study of Adolescent Health (Add Health Study) during the years 2001 to 2002 (Wave
      III, YAH) and 2007 to 2008 (Wave IV, AH). Multivariate logistic regression models
      were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of
      cigarette use behaviors according to age at the time of diagnosis with diabetes,
      after adjusting for demographic and selected behavioral factors. RESULTS: Of 12
      175 study participants, 2.6% reported having been diagnosed with diabetes up to
      AH. Early-onset diabetics (age at diagnosis <13 years) were more likely than non
      diabetics to report frequent cigarette smoking (smoking on >=20 days during the
      previous 30 days) in YAH (OR, 3.34; 95% CI, 1.27 to 8.79). On the other hand,
      late-onset diabetics (age at diagnosis >=13 years) were more likely than non
      diabetics to report heavy cigarette smoking (smoking >=10 cigarettes per day
      during the previous 30 days) in AH (OR, 1.54; 95% CI, 1.03 to 2.30). CONCLUSIONS:
      The current study indicated that diabetics are more likely than non-diabetics to
      smoke cigarettes frequently and heavily in YAH and AH. Effective smoking
      prevention and cessation programs uniquely focused on diabetics need to be
      designed and implemented.

PMID- 24137528
TI  - Socio-demographic characteristics and leading causes of death among the
      casualties of meteorological events compared with all-cause deaths in Korea, 2000
      2011.
AB  - OBJECTIVES: This study investigated the socio-demographic characteristics and
      medical causes of death among meteorological disaster casualties and compared
      them with deaths from all causes. METHODS: Based on the death data provided by
      the National Statistical Office from 2000 to 2011, the authors analyzed the
      gender, age, and region of 709 casualties whose external causes were recorded as
      natural events (X330-X389). Exact matching was applied to compare between deaths
      from meteorological disasters and all deaths. RESULTS: The total number of deaths
      for last 12 years was 2 728 505. After exact matching, 642 casualties of
      meteorological disasters were matched to 6815 all-cause deaths, which were
      defined as general deaths. The mean age of the meteorological disaster casualties
      was 51.56, which was lower than that of the general deaths by 17.02 (p<0.001). As
      for the gender ratio, 62.34% of the meteorological event casualties were male.
      While 54.09% of the matched all-cause deaths occurred at a medical institution,
      only 7.6% of casualties from meteorological events did. As for occupation, the
      rate of those working in agriculture, forestry, and fishery jobs was twice as
      high in the casualties from meteorological disasters as that in the general
      deaths (p<0.001). Meteorological disaster-related injuries like drowning were
      more prevalent in the casualties of meteorological events (57.48%). The rate of
      amputation and crushing injury in deaths from meteorological disasters was three
      times as high as in the general deaths. CONCLUSIONS: The new information gained
      on the particular characteristics contributing to casualties from meteorological
      events will be useful for developing prevention policies.

PMID- 24137529
TI  - A prospective cohort study on the relationship of sleep duration with all-cause
      and disease-specific mortality in the Korean Multi-center Cancer Cohort study.
AB  - OBJECTIVES: Emerging evidence indicates that sleep duration is associated with
      health outcomes. However, the relationship of sleep duration with long-term
      health is unclear. This study was designed to determine the relationship of sleep
      duration with mortality as a parameter for long-term health in a large
      prospective cohort study in Korea. METHODS: The study population included 13 164
      participants aged over 20 years from the Korean Multi-center Cancer Cohort study.
      Information on sleep duration was obtained through a structured questionnaire
      interview. The hazard ratios (HRs) and 95% confidence intervals (CIs) for
      mortality were estimated using a Cox regression model. The non-linear
      relationship between sleep duration and mortality was examined non-parametrically
      using restricted cubic splines. RESULTS: The HRs for all-cause mortality showed a
      U-shape, with the lowest point at sleep duration of 7 to 8 hours. There was an
      increased risk of death among persons with sleep duration of <=5 hours (HR, 1.21;
      95% CI, 1.03 to 1.41) and of >=10 hours (HR, 1.36; 95% CI, 1.07 to 1.72). In
      stratified analysis, this relationship of HR was seen in women and in
      participants aged >=60 years. Risk of cardiovascular disease-specific mortality
      was associated with a sleep duration of <=5 hours (HR, 1.40; 95% CI, 1.02 to
      1.93). Risk of death from respiratory disease was associated with sleep duration
      at both extremes (<=5 and >=10 hours). CONCLUSIONS: Sleep durations of 7 to 8
      hours may be recommended to the public for a general healthy lifestyle in Korea.

PMID- 24137530
TI  - A new disability-related health care needs assessment tool for persons with brain
      disorders.
AB  - OBJECTIVES: This study aimed to develop a health needs assessment (HNA) tool for
      persons with brain disorders and to assess the unmet needs of persons with brain
      disorders using the developed tool. METHODS: The authors used consensus methods
      to develop a HNA tool. Using a randomized stratified systematic sampling method
      adjusted for sex, age, and districts, 57 registered persons (27 severe and 30
      mild cases) with brain disorders dwelling in Seoul, South Korea were chosen and
      medical specialists investigated all of the subjects with the developed tools.
      RESULTS: The HNA tool for brain disorders we developed included four categories:
      1) medical interventions and operations, 2) assistive devices, 3) rehabilitation
      therapy, and 4) regular follow-up. This study also found that 71.9% of the
      subjects did not receive appropriate medical care, which implies that the
      severity of their disability is likely to be exacerbated and permanent, and the
      loss irrecoverable. CONCLUSIONS: Our results showed that the HNA tool for persons
      with brain disorders based on unmet needs defined by physicians can be a useful
      method for evaluating the appropriateness and necessity of medical services
      offered to the disabled, and it can serve as the norm for providing health care
      services for disabled persons. Further studies should be undertaken to increase
      validity and reliability of the tool. Fundamental research investigating the
      factors generating or affecting the unmet needs is necessary; its results could
      serve as basis for developing policies to eliminate or alleviate these factors.

PMID- 24137533
TI  - Predicting distribution of Aedes aegypti and Culex pipiens complex, potential
      vectors of Rift Valley fever virus in relation to disease epidemics in East
      Africa.
AB  - BACKGROUND: The East African region has experienced several Rift Valley fever
      (RVF) outbreaks since the 1930s. The objective of this study was to identify
      distributions of potential disease vectors in relation to disease epidemics.
      Understanding disease vector potential distributions is a major concern for
      disease transmission dynamics. METHODS: DIVERSE ECOLOGICAL NICHE MODELLING
      TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy
      (Maxent) approach for estimating distributions of potential RVF vectors in un
      sampled areas in East Africa. We modelled the distribution of two species of
      mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential
      maintenance and amplification of the virus, respectively. Predicted distributions
      of environmentally suitable areas in East Africa were based on the presence-only
      occurrence data derived from our entomological study in Ngorongoro District in
      northern Tanzania. RESULTS: Our model predicted potential suitable areas with
      high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex.
      Model performance was statistically significantly better than random for both
      species. Most suitable sites for the two vectors were predicted in central and
      northwestern Tanzania with previous disease epidemics. Other important risk areas
      include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley
      region of Kenya. CONCLUSION: Findings from this study show distributions of
      vectors had biological and epidemiological significance in relation to disease
      outbreak hotspots, and hence provide guidance for the selection of sampling areas
      for RVF vectors during inter-epidemic periods.

PMID- 24137534
TI  - A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent
      apoptosis.
AB  - mir-17-92, a potent polycistronic oncomir, encodes six mature miRNAs with complex
      modes of interactions. In the EMU-myc Burkitt's lymphoma model, mir-17-92
      exhibits potent oncogenic activity by repressing c-Myc-induced apoptosis,
      primarily through its miR-19 components. Surprisingly, mir-17-92 also encodes the
      miR-92 component that negatively regulates its oncogenic cooperation with c-Myc.
      This miR-92 effect is, at least in part, mediated by its direct repression of
      Fbw7, which promotes the proteosomal degradation of c-Myc. Thus, overexpressing
      miR-92 leads to aberrant c-Myc increase, imposing a strong coupling between
      excessive proliferation and p53-dependent apoptosis. Interestingly, miR-92
      antagonizes the oncogenic miR-19 miRNAs; and such functional interaction
      coordinates proliferation and apoptosis during c-Myc-induced oncogenesis. This
      miR-19:miR-92 antagonism is disrupted in B-lymphoma cells that favor a greater
      increase of miR-19 over miR-92. Altogether, we suggest a new paradigm whereby the
      unique gene structure of a polycistronic oncomir confers an intricate balance
      between oncogene and tumor suppressor crosstalk.
      DOI:http://dx.doi.org/10.7554/eLife.00822.001. 

PMID- 24137535
TI  - ATR/Mec1 prevents lethal meiotic recombination initiation on partially replicated
      chromosomes in budding yeast.
AB  - During gamete formation, crossover recombination must occur on replicated DNA to
      ensure proper chromosome segregation in the first meiotic division. We identified
      a Mec1/ATR- and Dbf4-dependent replication checkpoint in budding yeast that
      prevents the earliest stage of recombination, the programmed induction of DNA
      double-strand breaks (DSBs), when pre-meiotic DNA replication was delayed. The
      checkpoint acts through three complementary mechanisms: inhibition of Mer2
      phosphorylation by Dbf4-dependent Cdc7 kinase, preclusion of chromosomal loading
      of Rec114 and Mre11, and lowered abundance of the Spo11 nuclease. Without this
      checkpoint, cells formed DSBs on partially replicated chromosomes. Importantly,
      such DSBs frequently failed to be repaired and impeded further DNA synthesis,
      leading to a rapid loss in cell viability. We conclude that a checkpoint
      dependent constraint of DSB formation to duplicated DNA is critical not only for
      meiotic chromosome assortment, but also to protect genome integrity during
      gametogenesis. DOI:http://dx.doi.org/10.7554/eLife.00844.001. 

PMID- 24137536
TI  - A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes
      origin recognition complex formation.
AB  - In eukaryotes, DNA replication requires the origin recognition complex (ORC), a
      six-subunit assembly that promotes replisome formation on chromosomal origins.
      Despite extant homology between certain subunits, the degree of structural and
      organizational overlap between budding yeast and metazoan ORC has been unclear.
      Using 3D electron microscopy, we determined the subunit organization of metazoan
      ORC, revealing that it adopts a global architecture very similar to the budding
      yeast complex. Bioinformatic analysis extends this conservation to Orc6, a
      subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C
      terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper
      recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6
      associates with a previously uncharacterized domain of Orc3 and is required for
      ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier
      Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers,
      interfering with appropriate ORC functions.
      DOI:http://dx.doi.org/10.7554/eLife.00882.001. 

PMID- 24137537
TI  - A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables
      viral RNA dicing and antiviral immunity.
AB  - RNA interference defends against viral infection in plant and animal cells. The
      nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA
      virus Orsay, have recently emerged as a new animal model of host-virus
      interaction. Using a genome-wide association study in C. elegans wild populations
      and quantitative trait locus mapping, we identify a 159 base-pair deletion in the
      conserved drh-1 gene (encoding a RIG-I-like helicase) as a major determinant of
      viral sensitivity. We show that DRH-1 is required for the initiation of an
      antiviral RNAi pathway and the generation of virus-derived siRNAs (viRNAs). In
      mammals, RIG-I-domain containing proteins trigger an interferon-based innate
      immunity pathway in response to RNA virus infection. Our work in C. elegans
      demonstrates that the RIG-I domain has an ancient role in viral recognition. We
      propose that RIG-I acts as modular viral recognition factor that couples viral
      recognition to different effector pathways including RNAi and interferon
      responses. DOI:http://dx.doi.org/10.7554/eLife.00994.001. 

PMID- 24137538
TI  - Brahma is essential for Drosophila intestinal stem cell proliferation and
      regulated by Hippo signaling.
AB  - Chromatin remodeling processes are among the most important regulatory mechanisms
      in controlling cell proliferation and regeneration. Drosophila intestinal stem
      cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and
      serve as an excellent model for studying cell growth and regeneration. In this
      study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC
      proliferation and damage-induced midgut regeneration in a lineage-specific
      manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without
      Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm
      complex participates in ISC proliferation induced by the Scalloped-Yorkie
      transcriptional complex and that the Hippo (Hpo) signaling pathway directly
      restricted ISC proliferation by regulating Brm protein levels by inducing caspase
      dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted
      ISC proliferation. Our findings highlighted the importance of Hpo signaling in
      regulating epigenetic components such as Brm to control downstream transcription
      and hence ISC proliferation. DOI:http://dx.doi.org/10.7554/eLife.00999.001. 

PMID- 24137539
TI  - Slo1 is the principal potassium channel of human spermatozoa.
AB  - Mammalian spermatozoa gain competence to fertilize an oocyte as they travel
      through the female reproductive tract. This process is accompanied by an
      elevation of sperm intracellular calcium and a membrane hyperpolarization. The
      latter is evoked by K(+) efflux; however, the molecular identity of the potassium
      channel of human spermatozoa (hKSper) is unknown. Here, we characterize hKSper,
      reporting that it is regulated by intracellular calcium but is insensitive to
      intracellular alkalinization. We also show that human KSper is inhibited by
      charybdotoxin, iberiotoxin, and paxilline, while mouse KSper is insensitive to
      these compounds. Such unique properties suggest that the Slo1 ion channel is the
      molecular determinant for hKSper. We show that Slo1 is localized to the sperm
      flagellum and is inhibited by progesterone. Inhibition of hKSper by progesterone
      may depolarize the spermatozoon to open the calcium channel CatSper, thus raising
      [Ca(2+)] to produce hyperactivation and allowing sperm to fertilize an oocyte.
      DOI:http://dx.doi.org/10.7554/eLife.01009.001. 

PMID- 24137540
TI  - The human gut and groundwater harbor non-photosynthetic bacteria belonging to a
      new candidate phylum sibling to Cyanobacteria.
AB  - Cyanobacteria were responsible for the oxygenation of the ancient atmosphere;
      however, the evolution of this phylum is enigmatic, as relatives have not been
      characterized. Here we use whole genome reconstruction of human fecal and
      subsurface aquifer metagenomic samples to obtain complete genomes for members of
      a new candidate phylum sibling to Cyanobacteria, for which we propose the
      designation 'Melainabacteria'. Metabolic analysis suggests that the ancestors to
      both lineages were non-photosynthetic, anaerobic, motile, and obligately
      fermentative. Cyanobacterial light sensing may have been facilitated by
      regulators present in the ancestor of these lineages. The subsurface organism has
      the capacity for nitrogen fixation using a nitrogenase distinct from that in
      Cyanobacteria, suggesting nitrogen fixation evolved separately in the two
      lineages. We hypothesize that Cyanobacteria split from Melainabacteria prior or
      due to the acquisition of oxygenic photosynthesis. Melainabacteria remained in
      anoxic zones and differentiated by niche adaptation, including for symbiosis in
      the mammalian gut. DOI:http://dx.doi.org/10.7554/eLife.01102.001. 

PMID- 24137541
TI  - A microbial clock provides an accurate estimate of the postmortem interval in a
      mouse model system.
AB  - Establishing the time since death is critical in every death investigation, yet
      existing techniques are susceptible to a range of errors and biases. For example,
      forensic entomology is widely used to assess the postmortem interval (PMI), but
      errors can range from days to months. Microbes may provide a novel method for
      estimating PMI that avoids many of these limitations. Here we show that
      postmortem microbial community changes are dramatic, measurable, and repeatable
      in a mouse model system, allowing PMI to be estimated within approximately 3 days
      over 48 days. Our results provide a detailed understanding of bacterial and
      microbial eukaryotic ecology within a decomposing corpse system and suggest that
      microbial community data can be developed into a forensic tool for estimating
      PMI. DOI:http://dx.doi.org/10.7554/eLife.01104.001. 

PMID- 24137542
TI  - Expanding the olfactory code by in silico decoding of odor-receptor chemical
      space.
AB  - Coding of information in the peripheral olfactory system depends on two
      fundamental : interaction of individual odors with subsets of the odorant
      receptor repertoire and mode of signaling that an individual receptor-odor
      interaction elicits, activation or inhibition. We develop a cheminformatics
      pipeline that predicts receptor-odorant interactions from a large collection of
      chemical structures (>240,000) for receptors that have been tested to a smaller
      panel of odorants (~100). Using a computational approach, we first identify
      shared structural features from known ligands of individual receptors. We then
      use these features to screen in silico new candidate ligands from >240,000
      potential volatiles for several Odorant receptors (Ors) in the Drosophila
      antenna. Functional experiments from 9 Ors support a high success rate (~71%) for
      the screen, resulting in identification of numerous new activators and
      inhibitors. Such computational prediction of receptor-odor interactions has the
      potential to enable systems level analysis of olfactory receptor repertoires in
      organisms. DOI:http://dx.doi.org/10.7554/eLife.01120.001.

PMID- 24137543
TI  - A fair deal for PhD students and postdocs.
AB  - The relentless expansion that threatens the sustainability of biomedical research
      in the US takes a heavy toll on young researchers. 

PMID- 24137544
TI  - Nanoscale protein architecture of the kidney glomerular basement membrane.
AB  - In multicellular organisms, proteins of the extracellular matrix (ECM) play
      structural and functional roles in essentially all organs, so understanding ECM
      protein organization in health and disease remains an important goal. Here, we
      used sub-diffraction resolution stochastic optical reconstruction microscopy
      (STORM) to resolve the in situ molecular organization of proteins within the
      kidney glomerular basement membrane (GBM), an essential mediator of glomerular
      ultrafiltration. Using multichannel STORM and STORM-electron microscopy
      correlation, we constructed a molecular reference frame that revealed a laminar
      organization of ECM proteins within the GBM. Separate analyses of domains near
      the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM
      revealed a highly oriented macromolecular organization. Our analysis also
      revealed disruptions in this GBM architecture in a mouse model of Alport
      syndrome. These results provide the first nanoscopic glimpse into the
      organization of a complex ECM. DOI:http://dx.doi.org/10.7554/eLife.01149.001. 

PMID- 24137545
TI  - Structural basis for activation and non-canonical catalysis of the Rap GTPase
      activating protein domain of plexin.
AB  - Plexins are cell surface receptors that bind semaphorins and transduce signals
      for regulating neuronal axon guidance and other processes. Plexin signaling
      depends on their cytoplasmic GTPase activating protein (GAP) domain, which
      specifically inactivates the Ras homolog Rap through an ill-defined non-canonical
      catalytic mechanism. The plexin GAP is activated by semaphorin-induced
      dimerization, the structural basis for which remained unknown. Here we present
      the crystal structures of the active dimer of zebrafish PlexinC1 cytoplasmic
      region in the apo state and in complex with Rap. The structures show that the
      dimerization induces a large-scale conformational change in plexin, which opens
      the GAP active site to allow Rap binding. Plexin stabilizes the switch II region
      of Rap in an unprecedented conformation, bringing Gln63 in Rap into the active
      site for catalyzing GTP hydrolysis. The structures also explain the unique Rap
      specificity of plexins. Mutational analyses support that these mechanisms
      underlie plexin activation and signaling.
      DOI:http://dx.doi.org/10.7554/eLife.01279.001. 

PMID- 24137546
TI  - Inter-Golgi transport mediated by COPI-containing vesicles carrying small
      cargoes.
AB  - A core prediction of the vesicular transport model is that COPI vesicles are
      responsible for trafficking anterograde cargoes forward. In this study, we test
      this prediction by examining the properties and requirements of inter-Golgi
      transport within fused cells, which requires mobile carriers in order for
      exchange of constituents to occur. We report that both small soluble and membrane
      bound secretory cargo and exogenous Golgi resident glycosyl-transferases are
      exchanged between separated Golgi. Large soluble aggregates, which traverse
      individual stacks, do not transfer between Golgi, implying that small cargoes
      (which can fit in a typical transport vesicle) are transported by a different
      mechanism. Super-resolution microscopy reveals that the carriers of both
      anterograde and retrograde cargoes are the size of COPI vesicles, contain
      coatomer, and functionally require ARF1 and coatomer for transport. The data
      suggest that COPI vesicles traffic both small secretory cargo and steady-state
      Golgi resident enzymes among stacked cisternae that are stationary.
      DOI:http://dx.doi.org/10.7554/eLife.01296.001. 

PMID- 24137547
TI  - Sperm BerserKers.
AB  - Human sperm cells rely on an unusual type of potassium ion channel. 

PMID- 24137548
TI  - Checkpoint proteins come under scrutiny.
AB  - Details are emerging of the interactions between the kinetochore and various
      spindle checkpoint proteins that ensure that sister chromatids are equally
      divided between daughter cells during cell division. 

PMID- 24137549
TI  - When 19 is greater than 92.
AB  - The gene miR-17-92 encodes six different microRNAs, with one of these acting as
      an internal brake that opposes the oncogenic activity of the others in some
      cancer contexts. 

PMID- 24137550
TI  - A year in the life of eLife.
AB  - Improving the peer review process, overcoming the limitations of print journals
      and providing open access to the very best work in the life and biomedical
      sciences are three highlights of our first year. 

PMID- 24137552
TI  - Sense of achievement.
AB  - Computational techniques developed to predict if odorants will interact with
      receptors in the olfactory system have achieved a success rate of 70%. 

PMID- 24137554
TI  - Dopamine transporter imaging in psychogenic parkinsonism and neurodegenerative
      parkinsonism with psychogenic overlay: a report of three cases.
AB  - BACKGROUND: Differentiating psychogenic parkinsonism from neurodegenerative
      Parkinson's disease (PD) with psychogenic features is a diagnostic challenge.
      CASE REPORT: We report a detailed longitudinal clinical description of three
      cases presenting with suspected psychogenic parkinsonism. Dopamine transporter
      single-photon emission computed tomography (DAT-SPECT) was used as a supplemental
      diagnostic study and influenced clinical management. DISCUSSION: DAT-SPECT
      quantified the integrity of the striatal dopaminergic system in these cases of
      clinically uncertain parkinsonism and supported clinical decision-making.

PMID- 24137555
TI  - Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung
      cancer patients treated with definitive radiotherapy.
AB  - PURPOSE: To determine whether the maximum standardized uptake value (SUV) of
      [(18)F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio
      of lymph node to primary tumor (mSUVR) could be a prognostic factor for node
      positive non-small cell lung cancer (NSCLC) patients treated with definitive
      radiotherapy (RT). MATERIALS AND METHODS: A total of 68 NSCLC T1-4, N1-3, M0
      patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen
      based on overall survival (OS). Independent prognosticators were identified by
      Cox regression analysis. RESULTS: The most significant cutoff value for mSUVR was
      0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49%
      for those with mSUVR <= 0.9 (p = 0.01). In a multivariate analysis, including
      age, performance status, stage, use of chemotherapy, and mSUVR, only performance
      status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS.
      Two-year OS for patients with both good performance (Eastern Cooperative Oncology
      Group [ECOG] <= 1) and mSUVR <= 0.9 was significantly better than that for
      patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs.
      23%, p = 0.04). CONCLUSION: Our results suggested that the mSUVR was a strong
      prognostic factor among patients with lymph node positive NSCLC following RT.
      Addition of mSUVR to performance status identifies a subgroup at highest risk for
      death after RT.

PMID- 24137556
TI  - Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in
      patients with advanced maxillary sinus cancer.
AB  - PURPOSE: The optimal treatment of advanced maxillary sinus cancer has been
      challenging for several decades. Intra-arterial chemotherapy (IAC) for head and
      neck cancer has been controversial. We have analyzed the long-term outcome of
      neoadjuvant IAC followed by radiation therapy (RT) and surgery. MATERIALS AND
      METHODS: Twenty-seven patients with advanced maxillary sinus cancer were treated
      between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m(2)) was infused intra
      arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery
      was performed 3 to 4 weeks after completion of IAC and RT. RESULTS: At a median
      follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall
      survival in all patients were 63%. The 5-year rates of overall survival of stage
      T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients
      with disease recurrence had a local recurrence alone. The 5-year actuarial local
      control rates in patients with stage T3/T4, and in all patients were 20.0%,
      32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC
      and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to
      moderate late complications. The tumor extent (i.e., the involvement of either
      orbit and/or base of skull) appeared to be related with local recurrence.
      CONCLUSION: Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective
      to improve local tumor control in the patients with advanced maxillary sinus
      cancer. However, local failure was still the major cause of death. Further
      investigations are required to determine the optimal treatment schedule,
      radiotherapy techniques and chemotherapy regimens.

PMID- 24137557
TI  - Role of radiotherapy for pancreatobiliary neuroendocrine tumors.
AB  - PURPOSE: We investigated the role of radiotherapy (RT) for pancreatobiliary
      neuroendocrine tumors (PB-NETs). MATERIALS AND METHODS: We identified 9 patients
      with PB-NETs who received RT between January 2005 and March 2012. Of these 9
      patients, 4 were diagnosed with NETs in the pancreas and 5 were diagnosed with
      NETs in the gallbladder. All patients received RT to the primary tumor or
      resection bed with a median total irradiation dose of 50.4 Gy, with or without
      chemotherapy. RESULTS: The tumor response rate and tumor control rate in the RT
      field were 60% and 100 %, respectively. All 4 patients who underwent surgery had
      no evidence of disease in the RT field. Of the 5 patients who received RT to the
      primary gross tumor, 1 had complete response, 2 had partial response, and 2 had
      stable disease in the RT field. The median time to progression was 11 months. Of
      the 9 patients, four patients had no progression, and 5 patients had progression
      of disease (locoregional, 2; distant, 2; locoregional/distant, 1). Of the 4
      patients without progression, 3 were treated with RT in adjuvant or neoadjuvant
      setting, and one received RT to primary tumor. One patient experienced radiation
      induced duodenitis at 3 months after concurrent chemoradiation without treatment
      related mortality. CONCLUSION: RT can yield local control for advanced PB-NETs.
      RT should be considered an essential part of multimodality treatment in
      management of advanced PB-NETs.

PMID- 24137558
TI  - Invasion of the great vessels or atrium predicts worse prognosis in thymic
      carcinoma.
AB  - PURPOSE: We evaluated treatment outcomes of thymic carcinomas to determine
      prognostic factors for survival. MATERIALS AND METHODS: Between May 1988 and May
      2009, 41 patients had pathologic diagnosis of thymic carcinoma in Seoul National
      University Hospital, Seoul, Korea. Of these, 40 patients were followed up to 188
      months after treatment. The mean age of all patients was 58.3 years and male to
      female ratio was 23 to 17. RESULTS: Among 30 patients who underwent surgical
      resection, 26 achieved R0 resection and postoperative radiotherapy (PORT) was
      performed in 22 patients (73%). Various chemotherapeutic regimens were given with
      local treatment modalities, surgery and/or radiotherapy, in 12 patients. The 5
      year locoregional control (LRC), distant metastasis-free survival, progression
      free survival (PFS), and overall survival were 79.4%, 53.0%, 42.6%, and 63.6%,
      respectively. Patients with Masaoka stage I or II showed excellent prognosis of 5
      year PFS around 90%. In advanced stages, invasion of the great vessels or atrium
      by thymic carcinomas was negative prognostic factor for PFS in univariate
      analysis. Lymph node involvement was statistically significant factor for LRC and
      PFS. Local or regional recurrence was infrequent after surgical resection
      followed by PORT, while distant metastasis was the major component of treatment
      failure. CONCLUSION: Complete resection followed by PORT provided remarkable
      local control without severe acute toxicities in patients with stage II and
      favorable stage III thymic carcinoma. Invasion of the great vessels or atrium was
      statistically significant prognostic factor for PFS.

PMID- 24137559
TI  - Treatment results of breast cancer patients with locoregional recurrence after
      mastectomy.
AB  - PURPOSE: To analyze the results of locoregional and systemic therapy in the
      breast cancer patients with locoregional recurrence (LRR) after mastectomy.
      MATERIALS AND METHODS: Seventy-one patients who received radiotherapy for
      isolated LRR after mastectomy between January 1999 and December 2009 were
      retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide
      excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant
      hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including
      locoregional recurrence-free survival, disease-free survival (DFS), and overall
      survival (OS) and prognostic factors were analyzed. RESULTS: Median follow-up
      time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR,
      and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months,
      and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was
      86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy
      together showed better 5-year DFS and OS than the patients treated with
      locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p =
      0.022). In multivariate analysis, higher N stage at recurrence was a significant
      prognostic factor for DFS and OS. Disease free interval (<=30 months vs. >30
      months) from mastectomy to LRR was also significant for OS. The patients who
      received hormone therapy showed superior DFS and showed trend to better OS.
      CONCLUSION: DM was a major pattern of failure after the treatment of LRR after
      mastectomy. The role of systemic treatment for LRR after mastectomy should be
      investigated at prospective trials.

PMID- 24137560
TI  - Role of salvage radiotherapy for regional lymph node recurrence after radical
      surgery in advanced gastric cancer.
AB  - PURPOSE: To evaluate the role of salvage radiotherapy (RT) for the treatment of
      regional lymph node recurrence (RLNR) after radical surgery in advanced gastric
      cancer. MATERIALS AND METHODS: We retrospectively analyzed medical records of 26
      patients who underwent salvage treatment after diagnosis of RLNR between 2006 and
      2011. Patients with peritoneal seeding or distant metastasis were excluded.
      Eighteen patients received RT with or without chemotherapy and the other 8 did
      chemotherapy only without RT. A three-dimensional conformal RT was performed with
      median dose of 56 Gy (range, 44 to 60 Gy). Sixteen patients had fluoropyrimidine
      based chemotherapy, 5 did taxane-based chemotherapy, and irinotecan was applied
      in 4. RESULTS: With a median follow-up of 20 months (range, 5 to 57 months),
      median overall survival (OS) and progression-free survival (PFS) after diagnosis
      of RLNR were 29 months and 12 months in the entire patients, respectively.
      Radiotherapy (p = 0.007) and disease-free interval (p = 0.033) were statistically
      significant factors for OS in multivariate analysis. Median OS was 36 months in
      patients who received RT and 16 months in those who did not. Furthermore,
      delivery of RT (p < 0.001), complete remission after salvage treatment (p =
      0.040) and performance status (p = 0.023) were associated with a significantly
      better PFS. Gastrointestinal toxicities from RT were mild in most patients.
      CONCLUSION: Salvage RT combined with systemic chemotherapy may be an effective
      treatment managing RLNR from advanced gastric cancer.

PMID- 24137561
TI  - Comparison between preoperative and postoperative concurrent chemoradiotherapy
      for rectal cancer: an institutional analysis.
AB  - PURPOSE: To evaluate the treatment outcomes of preoperative versus postoperative
      concurrent chemoradiotherapy (CRT) on locally advanced rectal cancer. MATERIALS
      AND METHODS: Medical data of 114 patients with locally advanced rectal cancer
      treated with CRT preoperatively (54 patients) or postoperatively (60 patients)
      from June 2003 to April 2011 was analyzed retrospectively. 5-Fluorouracil (5-FU)
      or a precursor of 5-FU-based concurrent CRT (median, 50.4 Gy) and total
      mesorectal excision were conducted for all patients. The median follow-up
      duration was 43 months (range, 16 to 118 months). The primary end point was
      disease-free survival (DFS). The secondary end points were overall survival (OS),
      locoregional control, toxicity, and sphincter preservation rate. RESULTS: The 5
      year DFS rate was 72.1% and 48.6% for the preoperative and postoperative CRT
      group, respectively (p = 0.05, the univariate analysis; p = 0.10, the
      multivariate analysis). The 5-year OS rate was not significantly different
      between the groups (76.2% vs. 69.0%, p = 0.23). The 5-year locoregional control
      rate was 85.2% and 84.7% for the preoperative and postoperative CRT groups (p =
      0.98). The sphincter preservation rate of low-lying tumor showed significant
      difference between both groups (58.1% vs. 25.0%, p = 0.02). Pathologic tumor and
      nodal down-classification occurred after the preoperative CRT (53.7% and 77.8%,
      both p < 0.001). Acute and chronic toxicities were not significantly different
      between both groups (p = 0.10 and p = 0.62, respectively). CONCLUSION: The
      results confirm that preoperative CRT can be advantageous for improving down
      classification rate and the sphincter preservation rate of low-lying tumor in
      rectal cancer.

PMID- 24137562
TI  - Role of adjuvant postoperative external beam radiotherapy for well differentiated
      thyroid cancer.
AB  - PURPOSE: To analyze the outcome of adjuvant postoperative external beam
      radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). MATERIALS AND
      METHODS: We identified 84 patients treated with EBRT for WDTC from February 1981
      to December 2010. Among them, we analyzed 39 patients who received EBRT after
      initial radical surgery. Twenty-four females and 15 males were included. The
      median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid
      carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic
      T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five
      patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction
      size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. RESULTS: The median follow-up
      was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and
      locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively.
      Locoregional failures occurred in 5 and all failure sites were the neck node
      area. In univariate analysis, OS was significantly influenced by invasion of the
      trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by
      male (p = 0.020), gross residuum after resection (p = 0.002), close or positive
      tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p =
      0.040). No significant prognostic factor was identified in the multivariate
      analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or
      more toxicity. CONCLUSION: Our locoregional control rate of 87.2% is comparable
      to historical controls with surgery alone, even though our study had a large
      proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment
      option in patients with WDTC.

PMID- 24137563
TI  - Sorafenib-triggered radiation recall dermatitis with a disseminated exanthematous
      reaction.
AB  - Sorafenib is a multi-targeted kinase inhibitor, which is the current standard
      treatment for advanced hepatocellular carcinoma (HCC). Only one case of radiation
      recall dermatitis (RRD) associated with sorafenib has been reported so far. Our
      patient with recurrent HCC was treated with palliative radiotherapy (RT) for the
      chest wall mass. Sorafenib at 400 mg twice daily was begun on the day following
      RT. On the 14th day post-RT, an erythematous patch was observed on right chest
      wall which matched area previously irradiated. It was consistent with RRD. Ten
      days later, a disseminated exanthematous rash and severe pruritus occurred.
      Sorafenib was stopped and an oral antihistamine was prescribed to relieve
      symptoms. At the 1-week follow-up after the cessation of sorafenib, all symptoms
      were resolved. Physicians should be alert to this recall phenomenon as it can
      occur both in the skin and elsewhere and the occurrence of RRD may be
      unpredictable. 

PMID- 24137564
TI  - Timing of thoracic irradiation in limited stage small-cell lung cancer: is it
      still a star on the rise?

PMID- 24137565
TI  - Strategic Combination of DNA-Damaging Agent and PARP Inhibitor Results in
      Enhanced Cytotoxicity.
AB  - PARP inhibitors (PARPi) are under clinical trial for combination cancer
      chemotherapy. In the presence of a PARPi, PARP-1 binds DNA strand breaks but
      cannot produce poly(ADP-ribose) polymers or undergo auto-poly(ADP-ribosyl)ation.
      DNA binding is persistent, hindering DNA repair. Methylated bases formed as a
      result of cellular exposure to DNA-methylating agents are repaired by DNA
      polymerase beta (pol beta)-dependent base excision repair (BER) producing a 5'
      deoxyribose phosphate (5'-dRP) repair intermediate. PARP-1 binds and is activated
      by the 5'-dRP, and PARPi-mediated sensitization to methylating agents is
      considerable, especially in pol beta-deficient cells. Cells deficient in the BER
      factor XRCC1 are less sensitized by PARPi than are wild-type cells. PARPi
      sensitization is reduced in cells expressing forms of XRCC1 deficient in
      interaction with either pol beta or PARP-1. In contrast, agents producing
      oxidative DNA damage and 3'- rather than 5'-repair intermediates are modestly
      PARPi sensitized. We summarize PARPi experiments in mouse fibroblasts and confirm
      the importance of the 5'-dRP repair intermediate and functional pol beta and
      XRCC1 proteins. Understanding the chemistry of repair is key to enhancing the
      clinical success of PARPi. 

PMID- 24137566
TI  - Restriction-Spectrum Imaging of Bevacizumab-Related Necrosis in a Patient with
      GBM.
AB  - IMPORTANCE: With the increasing use of antiangiogenic agents in the treatment of
      high-grade gliomas, we are becoming increasingly aware of distinctive imaging
      findings seen in a subset of patients treated with these agents. Of particular
      interest is the development of regions of marked and persistent restricted
      diffusion. We describe a case with histopathologic validation, confirming that
      this region of restricted diffusion represents necrosis and not viable tumor.
      OBSERVATIONS: We present a case report of a 52-year-old man with GBM treated with
      temozolomide, radiation, and concurrent bevacizumab following gross total
      resection. The patient underwent sequential MRI's which included restriction
      spectrum imaging (RSI), an advanced diffusion-weighted imaging (DWI) technique,
      and MR perfusion. Following surgery, the patient developed an area of restricted
      diffusion on RSI which became larger and more confluent over the next several
      months. Marked signal intensity on RSI and very low cerebral blood volume (CBV)
      on MR perfusion led us to favor bevacizumab-related necrosis over recurrent
      tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.
      CONCLUSION AND RELEVANCE: Our report increases the number of pathologically
      proven cases of bevacizumab-related necrosis in the literature from three to
      four. Furthermore, our case demonstrates this phenomenon on RSI, which has been
      shown to have good sensitivity to restricted diffusion.

PMID- 24137568
TI  - Bacterial aetiological agents of intra-amniotic infections and preterm birth in
      pregnant women.
AB  - Infection-related preterm birth is a leading cause of infant mortality and
      morbidity; knowledge of bacterial populations invading the amniotic cavity and
      the routes of invasion is required to make progress in the prevention of preterm
      birth. Significant advances have been made in understanding bacterial communities
      in the vagina, but much less studied are intra-uterine bacterial populations
      during pregnancy. A systematic review of data published on the intra-uterine
      microbiome was performed; molecular information and summaries of species found in
      healthy individuals and in women with diagnosed infections served to construct a
      database and to analyse results to date. Thirteen studies fulfilled the review's
      inclusion criteria. The data of various investigations were collated, organized,
      and re-analyzed to achieve a more comprehensive understanding of microbial
      populations in the intra-amniotic space. The most common intra-amniotic bacterial
      taxa were species that can colonies the vagina in health and disease; there were
      others associated with the habitats of the mouth, gastrointestinal tract, and
      respiratory tract. The results suggest a central role for the ascending route of
      infections during pregnancy, and point to a possible secondary contribution via
      haematogenous invasion of the intra-amniotic space. The complete census of the
      intra-uterine microbiome awaits completion. 

PMID- 24137569
TI  - New insights in the interactions between African trypanosomes and tsetse flies.

PMID- 24137567
TI  - Autophagic clearance of bacterial pathogens: molecular recognition of
      intracellular microorganisms.
AB  - Autophagy is involved in several physiological and pathological processes. One of
      the key roles of the autophagic pathway is to participate in the first line of
      defense against the invasion of pathogens, as part of the innate immune response.
      Targeting of intracellular bacteria by the autophagic machinery, either in the
      cytoplasm or within vacuolar compartments, helps to control bacterial
      proliferation in the host cell, controlling also the spreading of the infection.
      In this review we will describe the means used by diverse bacterial pathogens to
      survive intracellularly and how they are recognized by the autophagic molecular
      machinery, as well as the mechanisms used to avoid autophagic clearance. 

PMID- 24137570
TI  - Seasonality and ambient temperature at time of conception in term-born
      individuals - influences on cardiovascular disease and obesity in adult life.
AB  - BACKGROUND: The influence of environmental conditions early in life - including
      temperature and season - on health later in life has so far not attracted much
      attention. OBJECTIVE: Using data from the Helsinki Birth Cohort Study of 13,345
      men and women, the influence of temperature and season at month of conception on
      birth weight, and on cardiovascular diseases and obesity-related traits in later
      life was studied. DESIGN: Linear regressions were fitted to examine the
      relationship between birth weight/obesity-related variables/hypertension and
      alternatively month of conception and average temperature of month of conception.
      The incidence of both coronary heart disease and cerebrovascular disease was
      assumed to follow a Weibull hazard model, and was modelled accordingly using
      survival analysis techniques. RESULTS: In women, unusually cold temperatures at
      month of conception predicted lower body mass index (BMI) and fat percentage, and
      protected from obesity. Warmer temperatures at month of conception were
      associated with higher risk for hypertension. In men, warmer temperatures around
      conception predicted lower BMI. No seasonal influences were detected on obesity
      related variables, nor were there seasonal or temperature mediated influences on
      birth weight, coronary heart disease or cerebrovascular disease observed.
      CONCLUSIONS: We suggest that ambient temperature has an influence on obesity
      related outcomes and hypertension. This merits further study, also with regard to
      other health outcomes and from a global perspective.

PMID- 24137571
TI  - Dramatic response to sirolimus in lymphangioleiomyomatosis.

PMID- 24137572
TI  - Severe airway injury due to alendronate aspiration.
AB  - Sequelae of foreign body aspiration can range from clinically silent and
      asymptomatic to immediate asphyxiation and death. Only two previous cases of
      bisphosphonate tablet aspiration have been reported. Ulcerative esophagitis, a
      known adverse effect of oral bisphosphonate formulations, occurs primarily with
      prolonged exposure of esophageal mucosa to the medication. Little is known about
      the effects of bisphosphonates on the airway mucosa. The authors present a case
      involving an 84-year-old woman who required multiple bronchoscopic debridements,
      intubation for airway protection and intensive care unit admission following
      airway injury believed to be due to delayed recognition of aspiration of an
      alendronate tablet. 

PMID- 24137573
TI  - Development of a web-based, work-related asthma educational tool for patients
      with asthma.
AB  - BACKGROUND: Asthma is a common chronic condition. Work-related asthma (WRA) has a
      large socioeconomic impact and is increasing in prevalence but remains under
      recognized. Although international guidelines recommend patient education, no
      widely available educational tool exists. OBJECTIVE: To develop a WRA educational
      website for adults with asthma. METHODS: An evidence-based database for website
      content was developed, which applied evidence-based website design principles to
      create a website prototype. This was subsequently tested and serially revised
      according to patient feedback in three moderated phases (one focus group and two
      interview phases), followed by face validation by asthma educators. RESULTS:
      Patients (n=10) were 20 to 28 years of age; seven (70%) were female, three (30%)
      were in university, two (20%) were in college and five (50%) were currently
      employed. Key format preferences included: well-spaced, bulleted text; movies (as
      opposed to animations); photos (as opposed to cartoons); an explicit listing of
      website aims on the home page; and an exploding tab structure. Participants
      disliked integrated games and knowledge quizzes. Desired informational content
      included a list of triggers, prevention/control methods, currently available
      tools and resources, a self-test for WRA, real-life scenario presentations,
      compensation information, information for colleagues on how to react during an
      asthma attack and a WRA discussion forum. CONCLUSIONS: The website met the
      perceived needs of young asthmatic patients. This resource could be disseminated
      widely and should be tested for its effects on patient behaviour, including job
      choice, workplace irritant/allergen avoidance and/or protective equipment, asthma
      medication use and physician prompting for management of WRA symptoms.

PMID- 24137574
TI  - Reference values for maximal inspiratory pressure: a systematic review.
AB  - BACKGROUND: Maximal inspiratory pressure (MIP) is the most commonly used measure
      to evaluate inspiratory muscle strength. Normative values for MIP vary
      significantly among studies, which may reflect differences in participant
      demographics and technique of MIP measurement. OBJECTIVE: To perform a systematic
      review with meta-analyses to synthesize MIP values that represent healthy adults.
      METHODS: A systematic literature search was conducted using Medline, EMBASE,
      Cochrane, Cumulative Index to Nursing and Allied Health (CINAHL) and Sport Discus
      databases. Two reviewers identified and selected articles, and abstracted data.
      Methodological quality was assessed using the Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS) tool. A random-effects model was used to calculate
      overall means and 95% CIs. RESULTS: Of 22 included articles, MIP data were
      synthesized according to age group and sex from six reports (n=840) in the meta
      analyses. The mean QUADAS score was 3.5 of 7. The age range was between 18 and 83
      years (426 men, 414 women). MIP began to decrease with age in the 40 to 60 years
      age range and continued to fall progressively with age. For the same age group,
      men tended to have higher MIPs than women. Sensitivity analysis of withdrawing
      studies from the meta-analysis identified one study that contributed more to
      heterogeneity in some age groups. DISCUSSION: MIP was higher in men and decreased
      with age, which was initially apparent in middle age. Several characteristics of
      participants and MIP technique influence values in healthy individuals.
      CONCLUSIONS: The present meta-analysis provides normative MIP values that are
      reflective of a large sample (n=840) and likely represents the broadest
      representation of participant characteristics compared with previous reports of
      normative data.

PMID- 24137575
TI  - Airway pressure and transpulmonary pressure during high-frequency oscillation for
      acute respiratory distress syndrome.
AB  - BACKGROUND: High-frequency oscillation (HFO) is used for the treatment of
      refractory hypoxic respiratory failure. OBJECTIVE: To demonstrate that the mean
      transpulmonary pressure (PL) cannot be inferred from mean airway pressure (mPaw).
      METHODS: In seven patients already undergoing HFO for refractory acute
      respiratory distress syndrome, esophageal pressure (Pes) was measured using an
      esophageal balloon catheter. Pleural pressure (Ppl) and PL were calculated from
      Pes. MAIN RESULTS: In the seven patients (mean [+/- SD] age 59 +/- 9 years)
      treated with HFO at 5 +/- 1 Hz and amplitude 75 +/- 10 cmH2O, the mPaw was 27 +/-
      6 cmH2O, Ppl was 9 +/- 6 cmH2O and PL was 18 +/- 11 cmH2O. Successful catheter
      placement and measurement of Pes occurred in 100% of subjects. There was no
      correlation between PL and mPaw. The majority of subjects required hemodynamic
      support during the use of HFO; the frequency and degree of support during the
      study period was no different than that before the study. CONCLUSION: The present
      report is the first to describe measuring Pes and calculating Ppl during HFO for
      acute respiratory distress syndrome. While both current guidelines and recent
      trials have titrated treatment based on mPaw and oxygenation, there is wide
      variability in PL during HFO and PL cannot be predicted from mPaw.

PMID- 24137576
TI  - Foreign-body aspiration in the adult: presentation and management.
AB  - Nonasphyxiating foreign-body aspiration in adults can be difficult to diagnose
      because the symptoms are nonspecific and chest x-rays may be normal due to
      organic composition of the foreign bodies. The diagnosis is often made via
      flexible bronchoscopy; however, debate remains as to whether rigid or flexible
      bronchoscopy is the optimal method of extraction. The authors describe a patient
      who was initially referred for assessment of a calcified left mainstem bronchus
      mass identified only on computed tomography scan of the thorax. The patient
      underwent flexible bronchoscopy and was discovered to have a bone fragment wedged
      in the bronchus for a duration of 22 years, which was successfully removed via
      rigid bronchoscope. 

PMID- 24137577
TI  - The role of 18F-FDG PET and 18F-FDG PET/CT in the evaluation of pediatric
      Hodgkin's lymphoma and non-Hodgkin's lymphoma.
AB  - Pediatric lymphomas (PL) are the third most common malignancy and account for 10%
      to 15% of all cancers in the pediatric age group. Accurate classification and
      staging are important for appropriate prognosis and treatment of pediatric
      Hodgkin's lymphoma (PHL) and non-Hodgkin's lymphomas (PNHL) and impact patient
      prognosis significantly. The role of fluorine-18-fluorodeoxyglucose positron
      emission tomography (18F-FDG PET) and 18F-FDG PET/computed tomography (18F-FDG
      PET/CT) in diagnosis, staging, localization of tumor radiotherapy, evaluation of
      treatment response and detection of recurrent tumors of PHL and PNHL is reviewed
      in this paper. The results of published 18F-FDG PET and 18F-FDG PET/CT studies in
      pediatric patients with HL and NHL were promising for initial diagnosis, for the
      localization of tumors, for radiation treatment and for early assessment of
      treatment response. However, as the sample size of these original articles was
      often small and a unified study design standard is lacking, more data are needed
      to better specify the role of 18F-FDG PET and 18F-FDG PET/CT in the management of
      PHL and PNHL. In conclusion, the 18F-FDG PET and 18F-FDG PET/CT appear superior
      to other imaging methods such as X-rays, CT, MRI and ultrasound, other nuclear
      medicine methods and bone marrow biopsy for the evaluation of pediatric
      lymphomas.

PMID- 24137578
TI  - Atherosclerotic inflammatory activity in the aorta and its correlation with aging
      and gender as assessed by 18F-FDG-PET.
AB  - Recent literature demonstrates the potential of fluorine-18 fluorodeoxyglucose
      positron emission tomography (18F-FDG-PET) to detect, localize, and quantify the
      degree of inflammatory changes in the arterial wall due to early atherosclerosis.
      Our aim was to assess the correlation between the age and 18F-FDG uptake of
      aortic segments and determine its correlation with respect to in both age and
      genders. Fluorine-18-FDG uptake in aortic segments in 143 subjects (58 men, 85
      women; ages 5-82 years) was evaluated in this study. Subjects were initially
      grouped according to the gender, and then by age (below or above 50) with at
      least 26 subjects per group. Mean standardized uptake value (SUV) of ascending
      aorta, arch, descending thoracic aorta, and abdominal aortic segments were
      calculated in each subject. Correlative analyses between age and mean SUV of
      aortic segments in all subjects were undertaken. Mean SUV between genders for all
      groups were also compared. There was a positive correlation between age and mean
      SUV of all aortic segments. The correlation values in all aortic segments were
      higher in subjects below 50 years old compared to those above 50 years in the
      entire group of patients as well as when they were subdivided and analyzed
      according to both genders (P<0.001). Descending thoracic and ascending aortic
      segments in men below 50 years of age had the highest correlation of 18F-FDG
      uptake and age (0.85 and 0.80, respectively) whereas abdominal aortic segments in
      men the above 50 years age group had the lowest correlation value (0.20).
      Comparison between mean SUV in four visible arterial segments between the two
      genders did not reveal any statistically significant difference. In conclusion,
      18F-FDG uptake in aortic segments increases with age irrespective of genders. The
      increase with age is more significant in younger subjects compared to older
      subjects for both men and women. This finding may indicate a deceleration in the
      inflammatory component of atherosclerosis with aging in older subjects.

PMID- 24137579
TI  - An evaluation of the predictive value of mid-treatment 18F-FDG-PET/CT scans in
      pediatric lymphomas and undefined criteria of abnormality in quantitative
      analysis.
AB  - Our purpose was to evaluate quantitative mid-treatment fluorine-18
      fluorodeoxyglucose (18F-FDG) PET/CT scans in predicting the quantitative result
      of the end of treatment 18F-FDG PET/CT scan. With approval of Emory's
      Institutional Review Board, data were extracted from 273 existing 18F-FDG PET/CT
      scans of 143 pediatric patients performed for evaluation of lymphoma. The
      inclusion criteria were the availability of an initial staging scan (D0) and a
      mid-treatment scan after 1 to 3 cycles of chemotherapy (D1) and a post-treatment
      scan (D2). Absolute and relative changed of D1 compared to D0 were measured and
      their values in predicting D3 values were determined. Analysis was performed on a
      lesion basis (N=78) in 18 patients with an average of 4.3 lesions per patients.
      Results showed that the predictive value depended on the value selected as
      significant for the predictors (D1 SUV and D1 %SUV), and on the limit between
      negative and positive selected for the predicted value D2 SUV. If the maximum
      SUV<2.0 in D2 was the limit for negative, the negative predictive value if D1<4
      was 0.84%. If positive was defined as D2>3.0, the positive predictive value of
      D1>4 was 100%. In that way outcome was predictable with absolute certainty in as
      many as 71% of the lesions with a single limit for D1 and D2. In conclusion, in
      this limited retrospective study the positive predictive value of the mid
      treatment scan, was high for the post-treatment result for patient and lesion
      response seen on D2.

PMID- 24137580
TI  - Prototype imaging protocols for monitoring the efficacy of iodine-131 ablation in
      differentiated thyroid cancer.
AB  - Whole-body and single photon emission tomography (SPET) images during sodium
      iodide-131 (Na131I) ablation are useful to confirm the efficacy of ablation using
      131I imaging. However, there have been no attempts to improve the quality of 131I
      imaging. We therefore investigated imaging protocols for 131I imaging in
      differentiated thyroid cancer (DTC). Phantoms containing 131I were used to
      simulate extra-thyroid beds and thyroid beds. To simulate extra-thyroid beds, a
      phantom containing 0.19, 0.37, 0.74 or 1.85 MBq was placed in the acquisition
      center. To simulate the thyroid beds, four phantoms were applied as normal
      thyroid tissue, and four phantoms containing 0.19, 0.37, 0.74 and 1.85 MBq were
      arranged around normal thyroid tissue as a cancer. Whole-body imaging was
      performed at different table speeds, and SPET data acquired with various pixel
      sizes were reconstructed using a filtered backed projection (FBP) and ordered
      subsets expectation maximization with 3-dimensional (OSEM-3D) algorithm. We
      measured full width at half maximum (FWHM) and % coefficient of variation (%CV).
      Patients were then examined based on the results of phantom studies. In
      extrathyroid beds, slower table speed in whole-body imaging improved %CV, but had
      little effect on FWHM. For SPET imaging OSEM-3D produced high-resolution and low
      noise images, and FWHM and %CV improved with smaller pixel size, as compared with
      FBP. In the thyroid beds, only the 1.85 MBq phantom could be confirmed on whole
      body imaging. Images by SPET had high FWHM and low %CV when the smaller pixel
      size and OSEM-3D were applied. Accumulation of <=1.85 MBq was detected with a
      smaller pixel size of <=4.8 mm and OSEM-3D. For Na131I ablation imaging, slower
      scan speed is suitable for whole-body imaging and smaller pixel size and OSEM-3D
      is appropriate for SPET imaging. In conclusion, we confirmed Na131I accumulation
      in thyroid beds using slower scan speed (<=15 cm/min) on whole-body imaging, and
      then accurate identification of Na131I accumulation using SPET and CT fusion
      imaging with smaller pixel size (<=4.8 mm) and OSEM-3D.

PMID- 24137581
TI  - Preparation of a prototype radioactive probe for treatment of lacrimal ducts
      stenosis and a study of its dose distribution.
AB  - Our aim was to prepare a radioactive lacrimal passages probe, study its dose
      distribution in a phantom and suggest security indexes and therapeutic effective
      doses for brachytherapy. We prepared the radioactive probes by laying 125I
      particles into plastic tubes. We conducted temperature tests, pressure tests,
      soak tests and shock tests, to obtain security indexes. The dose distributions in
      phantom and wax matrix were also detected, and the surface dose rates on
      different parts of the phantom and the dose absorbed by the operator were
      examined. The radioactive lacrimal passage probe demonstrated no form changes in
      temperature tests, pressure tests and soak tests when using a surface radioactive
      contamination dose lower than 185 Bq. The probe was waferinged in shock tests
      with a surface radioactive contamination dose lower than 185 Bq. The dose
      detection in the phantom and the wax matrix showed that for distances of 1 mm-12
      mm off the tube, there were statistical differences of the absorbed dose
      (P<0.05). However, for the range of 12 mm-40 mm, there was no statistical
      difference (P>0.05). The dose rates administered by the radioactive probe used
      for radiotherapy to the lacrimal passages were within safe limits both for the
      phantom (Sichuan Keyi Corporation, China) and the operator. In conclusion, our
      study showed that this prototype lacrimal passages probe can be a useful and
      effective method for clinical brachytherapy of lacrimal ducts stenosis.

PMID- 24137582
TI  - Association of hemodynamic response during dipyridamole stress testing with 99mTc
      MIBI SPET myocardial perfusion image findings.
AB  - The aim of this study was to assess whether there is an association between
      changes in the heart rate and blood pressure after dipyridamole stress and
      abnormal scan findings detected with gated technetium-99m methoxy
      isobutylisonitrile (99mTc-MIBI) myocardial perfusion imaging (MPI). A total of
      200 consecutive patients with known or suspected coronary artery disease
      underwent MPI using a 2 days stress/rest protocol. Heart rate (HR), blood
      pressure and electrocardiogram were monitored during the stress study.
      Dipyridamole-induced increase in HR ratio (peak HR/baseline HR) of more than 1.20
      and decrease in systolic blood pressure (SBP) of 10 mmHg or more were defined as
      a normal response. Low ejection fraction (EF) was defined as EF less than 45%.
      Semi-quantitative measures used include summed stress score (SSS), summed
      difference score (SDS), end systolic volume (ESV) and left ventricular ejection
      fraction (LVEF). Chi-square-and regression analysis was used to assess
      associations between the various hemodynamic parameters and MPI abnormalities.
      Our results showed that 75% of patients had abnormal scans. Statistically
      significant associations were observed between each of the following factors and
      abnormal scan findings: abnormal SBP response to dipyridamole (P=0.011),
      increased SSS (P=0.040) and low LVEF (P=0.012). A significant association was
      also observed between decreased HR response and low LVEF (P=0.012). In
      conclusion, this study demonstrated that an abnormal hemodynamic response during
      dipyridamole stress test was associated with abnormal myocardial perfusion
      imaging scan findings, low LVEF and SSS.

PMID- 24137583
TI  - The value of Tc-99m tetrofosmin scintimammography in the assessment of P
      glycoprotein in patients with breast cancer.
AB  - P-glycoprotein (Pgp) overexpression has been shown to be correlated with
      resistance to chemotherapy in patients with malignant breast tumors. The aim of
      our study was to investigate the role of technetium-99m-tetrofosmin (99mTc-TF) as
      a functional imaging agent reflecting Pgp expression in these tumors. We
      prospectively studied 28 patients (26 females, 2 males; mean age, 53.07+/-9.88
      years; range, 38 to 70 years) with breast cancer to ascertain the relationship
      between the degree of accumulation (lesion/nonlesion=L/NL) and percentage washout
      (WO%) rate of 99mTc-TF and expression of Pgp in tumor tissues. All patients
      received 555-740 MBq of 99mTc-TF intravenously at the arm controlateral to the
      suffering breast. Planar images were obtained 10 and 120 min post injection from
      prone lateral and anterior views with an acquisition time of 5 min. Visual and
      semiquantitative measurements were performed. The L/NL ratios and WO% rates were
      calculated semiquantitatively. Immunohistochemical studies were performed on
      paraffin sections using a monoclonal antibody, JSB-1. The L/NL ratios and WO%
      rates were related with the level of Pgp determined immunohistochemically. Our
      results showed an inverse correlation between the L/NL ratios of 99mTc-TF and the
      density of Pgp expression in tumor tissues, whereas there was no appreciable
      correlation between the tumor WO% rates of 99mTc-TF and the level of Pgp
      expression (P=0.275). The values for the L/NL ratios were significantly lower for
      those tumors expressing Pgp at high levels than those with intermediate or no Pgp
      expression (P<0.002 and P<0.04). In conclusion, although our results warrant
      further studies, our data strongly suggest that 99mTc-TF imaging is useful to
      noninvasively determine the presence of multidrug resistance in patients with
      breast cancer.

PMID- 24137584
TI  - Discrepancies and priorities in staging and restaging malignant lymphoma by SPET,
      SPET/CT, PET/CT and PET/MRI.
AB  - Due to the rapid development of modern imaging methods and also of medical
      oncology, there has been a significant progress in diagnosis and treatment of
      malignant lymphomas in the last few years. Nuclear medicine (NM) imaging methods
      gained new perspectives via the so called hybrid technologies-single-photon
      emission tomography combined with computed tomography (SPET/CT), positron
      emission tomography combined with computed tomography (PET/CT) and recently even
      positron emission tomography combined with magnetic resonance imaging (PET/MRI),
      which have led to a better image quality and diagnostic findings. Since SPET/CT
      evolved later than the "gold standard" 18F-FDG-PET/CT in lymphoma diagnostics,
      there are fewer studies with it, but it seems to be an excellent alternative to
      PET/CT. The role of PET/CT is confirmed up-to-date for typically 18F-FDG-avid
      lymphomas, in staging and restaging diffuse large B-cell and some aggressive
      follicular lymphomas, in a suspected relapse of treatment of both Hodgkin's and
      non-Hodgkin's lymphomas. There are many discussions about the "interim-PET" but
      the recent results indicate its important prognostic role for predicting disease
      free survival and the possibility to modify treatment intensity in order to
      reduce late side effects. On the other hand, the routine and approbated use of
      conventional morphologic imaging methods CT and MRI serve as a "reference
      standard" for the newer hybrid technologies not only in diagnostics but also in
      the cost-benefit ratio analysis and remain the basic imaging modalities when
      hybrid methods are not available. In conclusion, our review points at the main
      advantages and disadvantages of each NM method mentioned above in the diagnosis
      and follow-up of malignant lymphomas. Specifically, problems in differential
      diagnostics and further possibilities to better optimize the diagnostic and
      therapeutic algorithm are mentioned.

PMID- 24137585
TI  - Graves' disease in an adolescent with dual congenital ectopia and no orthotopic
      thyroid gland identified by Tc-99m-pertechnetate SPET/CT imaging.
AB  - This is the first case of Graves' disease in an adolescent with lingual and
      prelaryngeal dual congenital ectopia and no orthotopic thyroid gland identified
      by technetium-99m-pertechnetate (99mTcO-4) SPET/CT imaging in a 15 years old boy.
      After 8 weeks treatment with methimazole, Graves' disease subsided. Fine needle
      aspiration cytology of the mass revealed the normal colloid and normal follicular
      cells without an atypia or lymphoid elements, suggesting a benign ectopic thyroid
      gland. In conclusion, there is no report in the literature with DETT lingual and
      prelaryngeal absence of orthotopic thyroid tissue and Graves' disease as in our
      case. This case also highlights the potential ascendancy of 99mTcO-4 SPET/CT in
      diagnosing the DETT.

PMID- 24137586
TI  - Estimation of the level of anxiety in rats: differences in results of open-field
      test, elevated plus-maze test, and Vogel's conflict test.
AB  - We compared individual anxiety assessed by three standard tests, open-field test,
      elevated plus-maze test, and Vogel conflict drinking test, in the same animals.
      No significant correlations between the main anxiety parameters were found in
      these three experimental models. Groups of animals with high and low anxiety rats
      were formed by a single parameter and subsequent selection of two extreme groups
      (10%). It was found that none of the tests could be used for reliable estimation
      of individual anxiety in rats. The individual anxiety level with high degree of
      confidence was determined in high-anxiety and low-anxiety rats demonstrating
      behavioral parameters above and below the mean values in all tests used.
      Therefore, several tests should be used for evaluation of the individual anxiety
      or sensitivity to emotional stress. 

PMID- 24137587
TI  - Intersystem relationships of respiration and hemodynamics in the initial period
      of postural effects.
AB  - We studied the dependence of parameters of lung volumes and the elastic
      properties of the lungs on changes in the central hemodynamics occurring in the
      initial period of passive postural changes in cats. It was found that transition
      from the horizontal to head-up and head-down tilting was accompanied by opposite
      hemodynamic changes in the cranial and caudal parts of the body. Changes in lung
      compliance and functional residual capacity of the lungs were opposite and
      linearly depended on the intensity of hemodynamic shifts, which indicates passive
      character of the primary disorders primarily determined by a physical factor,
      gravity-dependent redistribution of body fluids. 

PMID- 24137588
TI  - Vasomotor activity of the aorta during chronic smoking modeling.
AB  - We studied vasomotor responses of aortic endothelium in a rat model of chronic
      smoking. It was found that long-term exposure to tobacco smoke (inhalation)
      impaired vasomotor function of the aortic endothelium leading to insufficient
      vasodilator activity and enhanced vasoconstriction. After the cessation of
      inhalations, vasomotor disturbances were not only preserved, but also exacerbated
      because of increased pathological endothelium-independent vasoconstriction. 

PMID- 24137589
TI  - Effect of long-term simulated weightlessness on surfactant and water balance in
      mouse lungs.
AB  - Weightlessness produces adaptive and maladaptive changes in the respiratory
      system. We assessed the effects of 30-day antiorthostatic hanging as a model of
      microgravity on the water balance in the lungs and surface activity and
      phospholipid composition of pulmonary surfactant in C57Bl/6 mice. Long-term
      antiorthostatic hanging increased water content in the lungs and reduced surface
      active properties of the surfactant. This was accompanied by an increase in the
      content of alveolar phospholipids and changes in their fractional composition
      (increase in the relative content of lysophosphatidylcholine and
      phosphatidylethanolamine). 

PMID- 24137590
TI  - Elevation of seizure threshold after intranasal administration of anti-glutamate
      antibodies to C57BL/6 mice.
AB  - The dose-dependent effect of intranasal administration of antibodies to glutamate
      on acute generalized epileptic activity was studied in C57Bl/6 mice. It was shown
      that pretreatment with antibodies in doses of 100, 300, and 500 MUg/kg 1 h before
      titration with convulsant pentylenetetrazole had anticonvulsant effects. This
      treatment was followed by an increase in the thresholds of clonic and tonic
      seizures with fatal outcome and lengthening of seizure latency. The most
      pronounced effect was observed in doses of 300 and 500 MUg/kg. Comparison of the
      anticonvulsant effect of antibodies in active immunization with glutamate-BSA
      conjugate and systemic intraperitoneal administration of purified anti-glutamate
      antibodies revealed advantages of intranasal administration.

PMID- 24137591
TI  - Effect of cobalt on parameters of the cardiovascular system in elementary school
      children.
AB  - High incidence of cobalt deficiency (89%) was found in 7-8-year-old girls
      residents of the Republic of Tatarstan. Significant correlations were revealed
      between parameters of physical development and cardiovascular system and hair
      cobalt content. These data suggest that positive balance of cobalt is essential
      for normal growth and development of child's body and function of the
      cardiovascular system.

PMID- 24137592
TI  - Relationship of blood levels of inflammatory and destructive biomarkers in
      coronary atherosclerosis with long-term results of surgical revascularization.
AB  - The relationships between blood levels of inflammatory and destructive biomarkers
      (TNF-alpha, IL-1beta, IL-6, IL-8, soluble CD40 ligand, high-sensitivity C
      reactive protein, endothelial adhesion molecules, matrix metalloproteinase 3 and
      9 and their tissue inhibitor type 1) were studied in men with coronary
      atherosclerosis before and 5 years after coronary artery bypass surgery. In men
      with unfavorable course of coronary atherosclerosis in the delayed period, the
      initial blood levels of C-reactive protein and TNF-alpha by 1.7 and 3.0 times
      surpassed those in patients with favorable course of the disease. Associations
      were revealed between elevated blood content of high-sensitivity C-reactive
      protein (p=0.01, odds ratio of 1.33) and IL-8 (p=0.02, odds ratio of 1.02) and
      deaths in the delayed period; IL-6 (p=0.01, odds ratio of 1.02) and cases of
      myocardial infarction; C-reactive protein (p=0.02, odds ratio of 1.24) and
      unfavorable course of the delayed period in general (death, myocardial
      infarction, worsening of angina pectoris functional class).

PMID- 24137593
TI  - Effects of antiglutamate antibodies on the development of stress response and
      neurotransmitter content in the hippocampus and hypothalamus of rats with
      different behavioral activity.
AB  - We studied the effects of intranasal administration of antiglutamate antibodies
      on the development of stress response and level of neurotransmitter amino acids
      and monoamines in brain structures of rats with different initial behavioral
      activity. The stress exposure was followed by significant changes in behavioral
      activity and concentration of neurotransmitters in rat hippocampus and
      hypothalamus. The changes in the level of neurotransmitter amino acids and
      monoamines were more pronounced in the hippocampus. Antiglutamate antibodies
      administered intranasally in a single dose of 250 MUg/kg immediately after stress
      exposure prevented the development of the stress response and normalized the
      level of neurotransmitters in the brain structures of rats. The effect of
      antibodies was the most pronounced in behaviorally active rats.

PMID- 24137594
TI  - Effects of regulatory peptides on the stress-induced changes of lipid metabolism
      in experimental animals.
AB  - Experiments on rats showed that restraint stress is associated with an increase
      in plasma level of nonesterified fatty acids, total cholesterol, triglycerides,
      VLDL, and LDL. Administration of opioid peptides DSLET and DAGO alleviated stress
      induced shifts in lipid metabolism. The concentrations of nonesterified fatty
      acids, total cholesterol, and triglycerides decreased and HDL content increased
      under these conditions. Treatment with dynorphin A (1-13) prevented a significant
      increase in the concentration of nonesterified fatty acids in blood plasma, but
      did not affect the content of triglycerides and total cholesterol. Hepatocyte
      growth factor had minor influence on the analyzed parameters. The observed
      effects can be related to the stress-limiting effect of opioids, in particular,
      attenuation of catecholamine influence on the lipid tissue and generation of LPO
      products that inhibit cholesterol-degrading enzyme. 

PMID- 24137595
TI  - Neuroprotective effects of individual or combined exposure to hypoxia and
      hypercapnia in the experiment.
AB  - We studied the effects of hypoxic, hypercapnic, and hypercapnic-hypoxic exposures
      on brain tolerance to ischemia. All respiratory training modes had a
      neuroprotective effect, but the most pronounced effect was observed after
      exposure to hypercapnic hypoxia. Experimental stroke in rats preliminary exposed
      to hypercapnic hypoxia was associated with minimal neurological deficit and motor
      coordination disturbances in comparison with training modes. 

PMID- 24137596
TI  - Protective effect of ARE-inducing phenol antioxidant TS-13 in chronic
      inflammation.
AB  - The protective effect of partially substituted monophenol TS-13 inducing the
      Nrf2/Keap1/ARE signaling system was studied on the model of chronic inflammation
      in vivo. It was found that during simulation of inflammation in an air pouch
      lined with synovial-like membrane, TS-13 did not affect the exudate volume,
      protein content, and cell count, but significantly reduced the intensity of
      oxidative metabolism in leukocytes of the exudate. In rheumatoid polyarthritis
      induced by heterologous collagen, TS-13 reduced the severity of clinical signs of
      inflammation only at the early stages, but inhibited H2O2 generation by monocytes
      and, partially, by blood neutrophils. These results suggest that the phlogolytic
      effect of the redox sensitive Nrf2/Keap1/ARE signaling system is less pronounced
      in chronic immune-mediated inflammatory processes than in acute inflammation.

PMID- 24137597
TI  - Effects of pharmacological activation of TRPM8 ion channels on the
      thermoregulatory responses during warming.
AB  - Preliminary non-thermal activation of cold-sensitive TRPM8 ion channel
      facilitates initiation of the heat-defense responses in homoiothermal animals by
      decreasing temperature threshold of the vasodilatory response. TRPM8 activation
      leads to earlier heat-initiated increase in oxygen consumption, but reduces its
      magnitude. Warming inhibits the lipolytic effect of menthol activation of TRPM8
      observed under thermoneutral conditions. Thus, modulation of the skin temperature
      afferent signal by ion channel agonist TRPM8 changes not only cold-defense, but
      also heat-defense responses of the body. 

PMID- 24137598
TI  - Androgen deficiency in male rats with prolonged neonatal streptozotocin diabetes.
AB  - We studied the diurnal dynamics of testosterone concentration in male rats with
      240-day neonatal streptozotocin-induced diabetes mellitus, which is similar to
      human type 2 diabetes mellitus. We also studied the effects of intranasal
      administration of luliberin on testosterone level and the regulation of
      activities of adenylate cyclase and stimulatory G-proteins in the testicles of
      diabetic and intact animals by human chorionic gonadotropin. In rats with
      neonatal diabetes, a decrease in the mean diurnal level of testosterone and its
      morning rise were observed. The increase in testosterone level 30 min after
      luliberin administration was significantly reduced in diabetic animals, but no
      differences in the response to luliberin were observed in intact and diabetic
      rats 2-6 h after the treatment. The stimulatory effects of human chorionic
      gonadotropin on adenylate cyclase activity and binding of guanosine triphosphate
      by stimulatory G-proteins were reduced in the plasma membranes from the testicles
      of rats with neonatal diabetes in comparison with control specimens. Therefore,
      rats with neonatal diabetes were characterized by androgen deficiency, which can
      be related to the impairment of hypothalamic-pituitary-gonadal axis and reduced
      sensitivity of the adenylate cyclase system in the testicles of diabetic rats to
      human chorionic gonadotropin. 

PMID- 24137599
TI  - Neuroprotective effects of dipeptide analogue of brain-derived neurotrophic
      factor GSB-106 in in vitro experiments.
AB  - Dimeric dipeptide GSB-106, a novel structural analogue of neurotrophin BDNF, in
      doses from 10(-5) to 10(-8) M protected cultured immortalized mouse hippocampal
      HT-22 neurons from H2O2 or glutamate damage. The neuroprotective effect of GSB
      106 was also shown on cultured SH-SY5Y human neuroblastoma cells after treatment
      with neurotoxin 6-hydroxidopamine. These data attest to functional similarity of
      GSB-106 and neurotrophin BDNF.

PMID- 24137600
TI  - Effects of phenazepam on the behavior of C57BL/6 and BALB/c mice in the open
      field test after naloxone pretreatment.
AB  - We studied the effects of phenazepam (0.075 mg/kg) after pretreatment (5 minutes
      before) with naloxone (10 mg/kg) on open-field behavior of C57Bl/6 and BALB/c
      mice. In ex vivo experiments, we studied the effects of naloxone (1 and 10 mg/kg)
      on receptor binding of [(3)H]-flunitrazepam by membranes of brain fraction
      (P1+P2) of C57Bl/6 and BALB/c mice. It was shown that naloxone increased motor
      activity in the open field in BALB/c mice and decreased this parameter in C57Bl/6
      mice. During combined treatment, naloxone potentiated the activating effects of
      phenazepam on the open-field behavior of BALB/c mice and slightly increased the
      sedative effect of this drug in C57Bl/6 mice. Naloxone stimulated reception of
      [(3)H]-flunitrazepam in BALB/c mice and slightly increased radioligand binding in
      C57Bl/6 mice. These data attest to enhanced reception in benzodiazepine site of
      GABAA-receptor under conditions of opioid receptor blockade, the presence of
      anxiolytic or sedative (depending on the phenotype of the response to emotional
      stress) effect of naloxone, and co-directed effects of naloxone and
      benzodiazepine tranquilizer on open-field behavior of C57Bl/6 and BALB/c mice. 

PMID- 24137601
TI  - Mechanisms of hemostimulating effect of Aconitum baicalense diterpene alkaloids.
AB  - A mixture of diterpene alkaloids of Aconitum baicalense exhibited pronounced
      regenerative hemostimulating properties on the model of cytostatic
      myelosuppression. The therapeutic effect is based on activation of hemopoietic
      progenitor cells against the background of increased feeder capacity of stromal
      compartment of the hemopoiesis-inducing microenvironment and decreased count of
      mesenchymal stem cells in the bone marrow.

PMID- 24137603
TI  - Effect of alpha1-adrenomimetic indralin on oxygen consumption by bone marrow
      cells in vitro.
AB  - In vitro experiments with excessive and normal oxygenation of the culture medium
      showed unchanged oxygen consumption by mouse bone marrow cells under the
      influence of radioprotector indralin belonging to alpha1-adrenomimetics (100
      MUg/ml). After exhaustion of oxygen in the medium below 10 MUM and progressive
      decrease in cellular respiration, indralin stimulated oxygen consumption by bone
      marrow cells by 1.5 times. The role of the observed effect of indralin in the
      realization of its radioprotective properties is discussed.

PMID- 24137602
TI  - Prospects of using benzodiazepines in complex therapy of poisonings with
      anticholinesterase agents.
AB  - The efficiency of benzodiazepines on mouse model of anticholinesterase poisoning
      was shown. The protective effects of clonazepam and midazolam were observed at
      high (1 TD50, incoordination) and medium (0.3 TD50) doses and the effects of
      phenazepam and diazepam were found only at high doses. Midazolam produced the
      most pronounced protective effect: administration of this drug significantly
      increased the protective index of atropine+HI-6 combination during poisoning. 

PMID- 24137604
TI  - Changes in oxidant and antioxidant status of females with experimental gestosis
      under the effect of GABA derivatives.
AB  - Experimental gestosis, modeled by replacement of drinking water with 1.8% NaCl
      solution, induced oxidative stress, which was seen from accumulation of MDA
      (secondary LPO product) and inhibition of SOD and glutathione peroxidase in the
      brain, liver, and uterus of animals with gestosis. Citrocard and saliphene (GABA
      derivatives) inhibited LPO (reduced MDA concentrations in the studied organs) and
      activated antioxidant enzymes in experimental gestosis.

PMID- 24137605
TI  - Anti-inflammatory activity of TS-13, ARE-inducing phenol antioxidant.
AB  - The protective effect of water-soluble TS-13 monophenol inducing the antioxidant
      responsive element (ARE) system was studied on the models of acute inflammation.
      Intragastric administration of TS-13 to rats significantly reduced the severity
      of acute aseptic inflammation induced by intravenous injection of zymosan
      particles: granulocyte blood count and volume density of infiltrates in the liver
      decreased on day 3, spontaneous production of activated oxygen metabolites and
      respiratory burst in blood granulocytes decreased on days 2 and 3. A single dose
      of TS-13 improved survival of mice with endotoxin shock induced by
      intraperitoneal injection of E. coli LPS. These results confirmed high anti
      inflammatory activity of TS-13. 

PMID- 24137606
TI  - Antimutagenic activity of wheat polypeptides in human cells exposed to cadmium
      chloride.
AB  - Antimutagenic effects of polypeptides isolated from Triticum kiharae wheat
      plantule extracts have been studied on human cells exposed to cadmium chloride.
      The most effective polypeptide Tk-AMP-BP beta -purothionin exhibited higher
      antimutagenic activity than wheat water extract and another peptide isolated from
      the same wheat species, Tk-AMP-gamma 2 defensin; it also produced a pronounced
      antioxidant effect. This polypeptide can be used as a preventive agent for
      reducing the mutagenic potential of some environmental pollutants and for
      correction of human diseases associated with the defense system defects.

PMID- 24137607
TI  - Effect of long-term stress on H3Ser10 histone phosphorylation in neuronal nuclei
      of the sensorimotor cortex and midbrain reticular formation in rats with
      different nervous system excitability.
AB  - The effects of long-term mental and pain stress on H3Ser10 histone
      phosphorylation in neurons of the the sensorimotor corex and midbrain reticular
      formation were studied 24 h, 2 weeks, and 2 months after exposure of rats
      differing by the nervous system excitability. Rats with high excitability
      threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the
      midbrain reticular formation neurons than rats with low excitability threshold.
      The sensorimotor cortical neurons of the two strains did not differ by this
      parameter. Stress led to a significant increase in the counts of immunopositive
      neuronal nuclei in rats with low excitability threshold: the parameter increased
      significantly in the sensorimotor cortex 24 h after exposure and normalized in 2
      weeks after neurotization. In the midbrain reticular formation of this rat strain
      stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks;
      the parameter normalized after neurotization in 2 months. Hence, genetically
      determined level of the nervous system excitability was essential for the basal
      level of neuron phosphorylation and for the time course of this process after
      long-term exposure to mental and pain stress, depending on the brain structure. A
      probable relationship between H3Ser10 histone phosphorylation process and
      liability to obsessive compulsive mental disorders in humans was discussed.

PMID- 24137608
TI  - Phenotypic differences between mdx black mice and mdx albino mice. Comparison of
      cytokine levels in the blood.
AB  - In mdx mice, mutation in the muscle protein dystrophin gene results in the
      development of chronic degeneration of the muscle tissue. We performed a
      comparative analysis of blood cytokine levels in mdx mice, classical black mice
      and mice with additional genetic defect responsible for the manifestations of
      oculocutaneous albinism. In mdx albino mice, the total pool of cytokines (IL-10,
      IL-6, IL-5, IL-2, IL-1alpha, IL-4, IL-17, granulocyte-macrophage growth factor,
      TNF-alpha, and IFN-gamma) was increased. This increase was not associated with
      selective release of one of the above cytokines into the blood. The fraction of
      pro-inflammatory cytokines (IL-6, IL-1alpha, TNF-alpha) was increased in the
      total pool and the percentage of antiinflammatory cytokines (IL-4) was reduced.
      Changes in cytokine pool probably reflect the differences in the severity of the
      pathological process in the muscle tissue of both genetic variations of mdx mice.

PMID- 24137609
TI  - "Finnish" mutations in LDL receptor gene: a rare cause of familial
      hypercholesterolemia in St. Petersburg and Petrozavodsk.
AB  - The search for two mutations, FH-Helsinki and FH-North Karelia, in LDL receptor
      gene was carried out in patients with familial hypercholesterolemia from St.
      Petersburg (80 families) and Petrozavodsk (80 families) using allele-specific PCR
      and analysis of single-stranded DNA fragment conformation polymorphism (SSCP
      analysis) with subsequent sequencing. The FH-North Karelia mutation was found in
      one family in St. Petersburg and in one family in Petrozavodsk, while FH-Helsinki
      mutation was not detected in any of the samples. Hence, the two "Finnish"
      mutations together responsible for 2/3 familial hypercholesterolemia cases in
      Finland were extremely rare in the Russian regions neighboring Finland.

PMID- 24137610
TI  - Molecular mechanisms of hormone resistance of breast cancer.
AB  - More than 70% malignant mammary tumors contain steroid hormone receptors; this
      suggests the possibility of hormone therapy in the majority of patients with
      breast cancer (BC). The main cause of inefficiency of hormone therapy in BC is
      hormone resistance (tumor resistance to hormonal cytostatics). Here we discuss
      the main mechanisms of hormone resistance of BC and the mechanisms underlying the
      formation of hormone resistance of the tumors are analyzed at the molecular
      level. The data on the signal pathways of estrogen receptors (ER), the key
      regulators of BC cell proliferation, are presented. The most important factors of
      BC hormone resistance are: high activity/expression of receptor tyrosine kinases;
      high activity of proteins regulating cell defense mechanisms (Akt PI3K, mTOR);
      changes in the activities of cell cycle regulator proteins (Myc, c-Fos, Cyclin
      D1). Our experiments have demonstrated that estrogen-independent BC cell growth
      is supported by VEGF/VEGFR2 and EGF/EGFR mitogenic signal pathways. Our data
      indicate that NF-kappaB transcription factor is directly involved in the
      regulation of hormone-resistant BC cell growth and survival, while NF-kappaB
      suppression determines cell sensitivity to apoptotic activity of antitumor
      compounds. On the whole, the results indicate good prospects of using EGFR, HER
      2/neu, mTOR, VEGFR, PI3K/Akt molecular pathways as targets for BC therapy,
      including therapy for BC resistant forms.

PMID- 24137611
TI  - In vitro study of interactions between silicon-containing nanoparticles and human
      peripheral blood leukocytes.
AB  - The effects of silicon dioxide-based nanoparticles on the viability and
      proliferative activity of human peripheral blood cultured lymphocytes were
      studied. All nanoparticles in a concentration of 100 MUg/ml produced a
      significant cytotoxic effect, its intensity depending on particles' structure:
      SiO2 nanoparticles were least toxic, while Ce3(+)-intercaled montmorillonite
      nanoparticles were most toxic. The cells died mainly by apoptosis and
      postapoptotic necrosis. Incubation with nanoparticles in a concentration of 100
      MUg/ml for 72 h caused death of all phytohemagglutinin-activated lymphocytes,
      while in concentrations of 1 and 10 MUg/ml the nanoparticles had no effect of
      proliferative activity of cells. The results suggest that the effects of
      nanoparticles on cells are determined by the nanoparticle concentration and size,
      as well as by their structure.

PMID- 24137612
TI  - Brain morphology imaging by 3D microscopy and fluorescent Nissl staining.
AB  - Modern optical methods (multiphoton and light-sheet fluorescent microscopy) allow
      3D imaging of large specimens of the brain with cell resolution. It is therefore
      essential to refer the resultant 3D pictures of expression of transgene, protein,
      and other markers in the brain to the corresponding structures in the atlas. This
      implies counterstaining of specimens with morphological dyes. However, there are
      no methods for contrasting large samples of the brain without their preliminary
      slicing. We have developed a method for fluorescent Nissl staining of whole brain
      samples. 3D reconstructions of specimens of the hippocampus, olfactory bulbs, and
      cortex were created. The method can be used for morphological control and
      evaluation of the effects of various factors on the brain using 3D microscopy
      technique. 

PMID- 24137613
TI  - Morphological validation of hydroxyethylstarch use during the acute period of
      severe brain injury.
AB  - The effects of 10% hydroxyethylstarch solution on the cerebral microcirculatory
      bed and the blood-brain barrier were studied in Wistar rats during the acute
      period of severe brain injury. Positive changes in the morphometric values of the
      cerebral capillaries were observed in animals receiving intravenous injections of
      the drug, which promoted reduction of vascular permeability and cerebral tissue
      edema. These results confirmed the efficiency of hydroxyethylstarch as a
      component of infusion therapy in patients with severe brain injury. 

PMID- 24137614
TI  - Structural characteristics of renomedullary interstitial cells of hypertensive
      ISIAH rats.
AB  - The structural characteristics of the renal medulla and its interstitial cells
      were studied in hypertensive ISIAH rats (in comparison with normotensive WAG
      rats) in order to clear out the role of the renomedullary interstitial cells in
      the mechanisms of AP regulation. Morphometric electron microscopic analysis and
      immunohistochemical studies in ISIAH rats detected the initial signs of the
      renomedullary sclerosis. The renomedullary interstitial cells of ISIAH rats were
      characterized by higher numerical density and were larger in size, with a higher
      volumic share of their secretory granules. These structural features of the
      studied cells were regarded as signs of their more intense functional activity
      aimed at hypertension suppression.

PMID- 24137615
TI  - The characterization of normal thyroid tissue by micro-FTIR spectroscopy.
AB  - In this paper, we report the spectral patterns of normal human thyroid tissue and
      methodology to interpret hyperspectral imaging data and protein conformational
      changes observed therein. Raw image datasets were imported into software written
      in-house in the MATLAB environment and processed to yield pseudo-color images of
      the tissue sections. All spectra were vector normalized, noise-filtered, and
      corrected for water-vapour contributions and scattering effects before being
      subjected to Hierarchical Cluster Analysis (HCA) and correlated with histological
      structures obtained from images of H&E-stained parallel tissue sections. We
      successfully identified a protein structural heterogeneity that can be correlated
      with the spatially resolved amount of iodine in the thyroglobulin structure of
      colloids and follicular cells. 

PMID- 24137616
TI  - [Physiological response to stress caused by neuronal damage].

PMID- 24137617
TI  - [Problems in clinical tests using saliva and the future prospects for alternative
      methods for pharmacokinetic blood tests].

PMID- 24137618
TI  - Reply by authors.

PMID- 24137619
TI  - Biomedical institutions join forces to fight cancer.

PMID- 24137620
TI  - 30 year-old male with headaches.

PMID- 24137621
TI  - A 78-year-old male with a right occipital lesion.

PMID- 24137622
TI  - An unusual cause of lumbar radiculopathy.

PMID- 24137623
TI  - The mummy returns... and sheds new light on old questions.
AB  - Whether as the ancient Egyptian crocodile-god Sobek, a terrifying predator of
      African waterways, or simply as a premium handbag leather, the Nile crocodile
      (Crocodylus niloticus) has long held the fascination of mankind. Despite 200
      years of study, however, uncertainty remains as to its taxonomy. While resolving
      such issues are key to understanding the origins and biogeography of the so
      called true crocodiles of genus Crocodylus, given widespread ongoing range
      contraction, such issues are paramount for design of future conservation
      strategies. In this issue of Molecular Ecology, Hekkala et al. (2011) apply
      analysis of modern, historic and ancient DNA (aDNA) to the questions, with far
      reaching implications. First they demonstrate that, as currently described, the
      Nile crocodile is paraphyletic, with individuals from the east and western clades
      separated by a number of New World crocodile species. The consequences of this
      finding are as important for conservation efforts as for their impact on
      crocodile taxonomy. Furthermore, they strike at the heart of the long-standing
      debate over whether aDNA analysis of ancient Egyptian mummies is scientifically
      sound.

PMID- 24137624
TI  - American Genetic Association presents the annual Stephen J. O'Brien Award.

PMID- 24137625
TI  - Response to letters regarding article, "Duration of cardiopulmonary resuscitation
      and illness category impact survival and neurologic outcomes for in-hospital
      pediatric cardiac arrests".

PMID- 24137626
TI  - Author response.

PMID- 24137627
TI  - Author response.

PMID- 24137628
TI  - Novel carbon nanotube-conjugated polymer nanohybrids produced by multiple polymer
      processing.
AB  - We describe two methods in which we manipulate the binding of multiple conjugated
      polymers to single-walled carbon nanotubes (SWNTs) to produce new and novel
      nanostructures. One method fi rst utilizes the selective binding of poly(9,9
      dioctylfluorenyl-2,7-diyl) (PFO) to a narrow distribution of semiconducting SWNTs
      and then uses a polymer exchange to transfer this purity to other nanotube
      polymer combinations, using technologically useful polymers such as poly(3
      hexylthiophene) (P3HT) and poly(9,9'-dioctylfluoreneco -benzothiadiazole) (F8BT)
      as fi rst examples. The other method involves controlling the competitive binding
      of P3HT and F8BT to SWNTs to produce coaxial nanostructures consisting of both
      polymers simultaneously bound in ordered layers. We show that these two simple
      solution-processing techniques can be carried out sequentially to afford new dual
      polymer nanostructures comprised of a semiconducting SWNT of a single chirality.
      This allows the favorable properties of both polymers and purified semiconducting
      SWNTs to be implemented into potentially highly efficient organic photovoltaic
      devices.

PMID- 24137629
TI  - Reply to Roberts et al.: A subdecadal record of paleoclimate around the Youngest
      Toba Tuff in Lake Malawi.

PMID- 24137630
TI  - Reply to Henrich and Silk: Toward a unified explanation for apes and humans.

PMID- 24137631
TI  - Reply to van Leeuwen et al.: Planning for agricultural adaptation to climate
      change and its consequences for conservation.

PMID- 24137632
TI  - Retraction notice to "M-CSF deficiency leads to reduced metallothioneins I and II
      expression and increased tissue damage in the brain stem after 6-
      aminonicotinamide treatment" Exp Neurol 176 (2002) 308-321.

PMID- 24137633
TI  - Response to are observational studies more informative than randomized controlled
      trials in hypertension? Pro side of the argument.

PMID- 24137634
TI  - Response to are observational studies more informative than randomized controlled
      trials in hypertension? Con side of the argument.

PMID- 24137635
TI  - Reply: To PMID 23578672.

PMID- 24137636
TI  - Reply: To PMID 23493893.

PMID- 24137637
TI  - [Stents in visceral medicine].

PMID- 24137638
TI  - [The patient rights law - old wine in new bottles?].

PMID- 24137639
TI  - Diego Rivera's fresco and the case taken from Morgagni's De sedibus.
AB  - The fresco by Diego Rivera (1886 to 1957) on the history of cardiology was
      displayed at the "Instituto Nacional de Cardiologia" of Mexico City at the time
      of inauguration on April 14, 1944. Some of the most important masters of the
      Padua Medical School were depicted, namely Vesalius, Harvey, and Morgagni. There
      is a vivid description of the anatomoclinical method introduced by Giovanni
      Battista Morgagni (1682 to 1771), when he was professor of Theoretical Medicine
      first and then of Anatomy at the University of Padua (1711 to 1771). By reading
      Morgagni's De sedibus, we found the case of aortic syphilitic aneurysm that
      corresponds perfectly with the one represented in Diego Rivera's mural. In the
      Museum of Pathological Anatomy of the Padua University, an anatomical specimen
      that displays the same lesion is preserved, and we have performed a computed
      tomography scan to analyze the state of the heart and aneurysm, thus finding
      diffuse calcific deposits of aorta and pericardium. In conclusion, in Diego
      Rivera's fresco the clinicopathologic method of Morgagni is well represented and
      the case of syphilitic aneurysm, reported by Morgagni in his De sedibus,
      depicted.

PMID- 24137640
TI  - Hepatosplenic T-cell lymphoma appearing in the peripheral blood.

PMID- 24137641
TI  - Philadelphia chromosome positive acute B-lymphoblastic leukemia with extreme
      leukocytosis.

PMID- 24137642
TI  - Identified intimate partner violence (IPV) as a risk for women in contracting
      HIV/AIDS and other sexually transmitted disease.

PMID- 24137643
TI  - Seismic hazards: Seconds count.

PMID- 24137644
TI  - History: Great myths die hard.

PMID- 24137645
TI  - Quantum mechanics: Waterloo gets physical.

PMID- 24137646
TI  - Science without borders.

PMID- 24137647
TI  - Dangerous work.

PMID- 24137648
TI  - Cross the road.

PMID- 24137649
TI  - Retraction notice to "Treatment of aortic arch aneurysms with a modular
      transfemoral multibranched stent-graft: initial experience". J Thorac Cardiovasc
      Surg 2013;145: S110-7.

PMID- 24137650
TI  - Author response.

PMID- 24137651
TI  - [Control and Prokrustes].

PMID- 24137652
TI  - [The consent of the patient].

PMID- 24137653
TI  - Author response.

PMID- 24137654
TI  - [Tax return--health savings tax--exemption for workplace health promotion].

PMID- 24137655
TI  - Questions raised over Iraq congenital birth defects study.

PMID- 24137656
TI  - India looks to a new course to fix rural doctor shortage.

PMID- 24137657
TI  - Reply to Tall et al.: Dictyostelium Ric8 does not have a chaperoning  function
      during development and chemotaxis.

PMID- 24137663
TI  - Reply to Cauwels et al.: Of men, not mice, and inflammation.

PMID- 24137667
TI  - GTKDynamo: a PyMOL plug-in for QC/MM hybrid potential simulations.
AB  - Hybrid quantum chemical/molecular mechanical (QCMM) potentials are very powerful
      tools for molecular simulation. They are especially useful for studying processes
      in condensed phase systems, such as chemical reactions that involve a relatively
      localized change in electronic structure and where the surrounding environment
      contributes to these changes but can be represented with more computationally
      efficient functional forms. Despite their utility, however, these potentials are
      not always straightforward to apply since the extent of significant electronic
      structure changes occurring in the condensed phase process may not be intuitively
      obvious. To facilitate their use, we have developed an open-source graphical plug
      in, GTKDynamo that links the PyMOL visualization program and the pDynamo QC/MM
      simulation library. This article describes the implementation of GTKDynamo and
      its capabilities and illustrates its application to QC/MM simulations.

PMID- 24137668
TI  - GALAMOST: GPU-accelerated large-scale molecular simulation toolkit.
AB  - GALAMOST [graphics processing unit (GPU)-accelerated large-scale molecular
      simulation toolkit] is a molecular simulation package designed to utilize the
      computational power of GPUs. Besides the common features of molecular dynamics
      (MD) packages, it is developed specially for the studies of self-assembly, phase
      transition, and other properties of polymeric systems at mesoscopic scale by
      using some lately developed simulation techniques. To accelerate the simulations,
      GALAMOST contains a hybrid particle-field MD technique where particle-particle
      interactions are replaced by interactions of particles with density fields.
      Moreover, the numerical potential obtained by bottom-up coarse-graining methods
      can be implemented in simulations with GALAMOST. By combining these force fields
      and particle-density coupling method in GALAMOST, the simulations for polymers
      can be performed with very large system sizes over long simulation time. In
      addition, GALAMOST encompasses two specific models, that is, a soft anisotropic
      particle model and a chain-growth polymerization model, by which the hierarchical
      self-assembly of soft anisotropic particles and the problems related to
      polymerization can be studied, respectively. The optimized algorithms implemented
      on the GPU, package characteristics, and benchmarks of GALAMOST are reported in
      detail.

PMID- 24137670
TI  - Reply to Wolever.

PMID- 24137684
TI  - [Pay for Performance: please test, but correctly].

PMID- 24137685
TI  - Images in anesthesiology: shear wave elastography: novel technology for
      ultrasound-guided regional anesthesia.

PMID- 24137686
TI  - [Hospitals with poor quality should no longer provide the services].

PMID- 24137688
TI  - [Pay for performance only as an additional element].

PMID- 24137690
TI  - [P4P only useful on a system level].

PMID- 24137691
TI  - [Hamstring-graft increases infection risk].

PMID- 24137692
TI  - [Clinical judgement or pressure measurement?].

PMID- 24137693
TI  - [Wire instead of cable!].

PMID- 24137694
TI  - [Sliding prosthesis: what do we really know?].

PMID- 24137695
TI  - Reply to JL Leroy et al.

PMID- 24137696
TI  - Reply to ML Zwinkels et al.

PMID- 24137697
TI  - Bull's eye! Lyme disease awareness.

PMID- 24137698
TI  - [Operative access routes in orthopedics and traumatology - the legendary classic 
      completely revised and expanded].

PMID- 24137699
TI  - A record number of fatalities in many categories of patients treated with
      deferasirox: loopholes in regulatory and marketing procedures undermine patient
      safety and misguide public funds? Author's response.

PMID- 24137700
TI  - Reply: To PMID 23624622.

PMID- 24137701
TI  - Reed Sternberg cells in bone marrow touch imprints.

PMID- 24137702
TI  - Pure white cell aplasia in a patient with thymic carcinoma.

PMID- 24137703
TI  - The possible use of combined electrical impedance and ultrasound velocity
      measurements for the non-invasive measurement of temperature during mild
      hyperthermia.
AB  - This paper explores the possibility of using combined measurements of electrical
      impedance and changes in ultrasound time of flight for determining deep body
      temperature during mild hyperthermia. Simultaneous electrical impedance spectra
      (1 kHz-1024 kHz) and ultrasound time-of-flight measurements were made on layered
      sheep liver and fat tissue samples as the temperature was increased from 30-50 
      degrees C. The change in propagation velocity for 100% fat and 100% liver samples
      was found to vary linearly with temperature and the temperature coefficient of
      the time-of-flight was shown to vary linearly with the % fat in the sample
      (0.009%  degrees C-1%-1). Tetrapolar impedance measurements normalized to 8 kHz
      were shown to have a small sensitivity to temperature for both liver (0.001% 
      degrees C-1 <= 45  degrees C) and fat (0.002%  degrees C-1 <= 512 kHz) and the
      best linear correlation between the normalized impedance and the % fat in the
      sample was found at 256 kHz (gradient 0.026%-1, r2 = 0.65). A bootstrap analysis
      on 15 layered tissue samples evaluated using the normalized impedance at 256 kHz
      to determine the % fat in the sample and the temperature coefficient of the time
      of flight to determine the temperature. The results showed differences (including
      some large differences) between the predicted and measured temperatures and an
      error evaluation identified the possible origins of these.

PMID- 24137704
TI  - X-ray fluorescence measurements of arsenic micro-distribution in human nail
      clippings using synchrotron radiation.
AB  - Arsenic (As) distribution in nail clippings from three healthy human subjects was
      investigated using the microbeam experimental setup of the hard x-ray micro
      analysis (HXMA) beamline from the Canadian Light Source (CLS) synchrotron. A pair
      of toenail and fingernail clippings was collected from each of three subjects
      (one contributed two fingernail clippings). The fingernail and toenail clippings
      were embedded in polyester resin and cut in cross-sectional slices with an
      average thickness of 270 um. Nine nail clipping cross sections were analyzed from
      the three subjects. The same method was used to produce five cross sections of
      nail phantom clippings with concentrations of As ranging from 0 to 20 ug g-1, in
      increments of 5 ug g-1. These samples were used to produce a calibration line for
      the As Kalpha peak. The energy of the x-ray beam was set at 13 keV for optimal
      excitation of As and the beam size was 28 * 10 um2. Each sample was analyzed
      using a point-by-point scanning technique in a 45 degrees  beam-sample and 90
      degrees  beam-detector geometry. The dwelling time was set at 30 s for the human
      nail clippings and 20 s for the nail phantom clippings, using a step size of 50
      um in both the horizontal and vertical directions for all samples. As
      concentration for each point was calculated based on the calibration line
      parameters and the fitted amplitude of the observed As Kalpha peak. As
      concentration maps were produced for each nail clipping cross section. The maps
      show that small regions (<0.1 mm2) with higher As concentrations (>1 ug g-1) are
      located predominantly in the ventral and dorsal layers of the nail. The results
      are in agreement with findings reported in a recent study and can be linked to
      nail histology and keratin structure.

PMID- 24137705
TI  - The dynamics of carbon dioxide equilibration after alterations in the respiratory
      rate.
AB  - Manual or automated control of mechanical ventilation can be realized as an open
      or closed-loop system for which the regulation of the ventilation parameters
      ideally is tuned to the dynamics and equilibration time of the biological system.
      We investigated the dynamic, transient state and equilibration time (teq) of the
      CO2 partial pressure (PCO2) after changes in the respiratory rate (RR). In 17
      anaesthetized patients without known history of lung disease, respiratory rate
      was alternately increased and decreased and end-tidal CO2 partial pressures
      (PetCO2) were measured. Linear relations were found between DeltaRR and PetCO2
      changes (DeltaPetCO2 = 0.3 - 1.1 DeltaRR) and between DeltaRR and teq for
      increasing and decreasing RR (teq(hypervent) = 0.5 |DeltaRR|, teq(hypovent) = 0.7
      |DeltaRR|). Extrapolation of the transition between two PCO2 steady-states
      allowed for the prediction of the new PCO2 steady-state as early as 0.5  teq with
      an error <4 mmHg. At bedside or in automated ventilation systems, the linear
      dependencies between DeltaRR and DeltaPCO2 and between DeltaRR and teq as well as
      early steady-state prediction of PCO2 could be used as a guidance towards a
      timing and step size regulation of RR that is well adapted to the biological
      system.

PMID- 24137706
TI  - Compressed sampling for boundary measurements in three-dimensional electrical
      impedance tomography.
AB  - Electrical impedance tomography (EIT) utilizes electrodes on a medium's surface
      to produce measured data from which the conductivity distribution inside the
      medium is estimated. For the cases that relocation of electrodes is impractical
      or no a priori assumptions can be made to optimize the electrodes placement, a
      large number of electrodes may be needed to cover all possible imaging volume.
      This may occur in dynamically varying conductivity distribution in 3D EIT. Three
      dimensional EIT then requires inverting very large linear systems to calculate
      the conductivity field, which causes significant problems regarding storage space
      and reconstruction time in addition to that data acquisition for a large number
      of electrodes will reduce the achievable frame rate, which is considered as major
      advantage of EIT imaging. This study proposes an idea to reduce the
      reconstruction complexity based on the well-known compressed sampling theory. By
      applying the so-called model-based CoSaMP algorithm to large size data collected
      by a 256 channel system, the size of forward operator and data acquisition time
      is reduced to those of a 32 channel system, while accuracy of reconstruction is
      significantly improved. The results demonstrate great capability of compressed
      sampling for overriding the challenges arising in 3D EIT.

PMID- 24137707
TI  - Response.

PMID- 24137708
TI  - Response.

PMID- 24137709
TI  - Response.

PMID- 24137710
TI  - Response.

PMID- 24137711
TI  - Bob Carlyon.

PMID- 24137712
TI  - Development of test fixture for measurement of dielectric properties and its
      verification using animal tissues.
AB  - The electromagnetic compatibility of implantable or wearable medical devices has
      often been evaluated using human phantoms to electrically mimic biological
      tissues. However, no currently existing test fixture can measure the electrical
      characteristics of gel-like materials. In this paper, we report the development
      of a new test fixture that consists of a coaxial tube whose outer conductor is
      divided along the axial direction into two sections, which facilitates filling
      and removal of gel-like materials in order to measure their electrical
      characteristics. Using this test fixture, we measured the electrical
      characteristics of a cow's muscular tissues up to 1 h post-mortem; these
      measurements allowed us to obtain the relative permittivity and conductivity of
      the biological tissue, which should help to enable the design of new human
      phantoms.

PMID- 24137713
TI  - In response.

PMID- 24137715
TI  - Infectious disease/CDC update. Update on emerging infections: news from the
      Centers for Disease Control and Prevention.

PMID- 24137714
TI  - Reconstruction of normal and abnormal gastric electrical sources using a
      potential based inverse method.
AB  - The use of cutaneous recordings to non-invasively characterize gastric slow waves
      has had limited clinical acceptance, primarily due to the uncertainty in relating
      the recorded signal to the underlying gastric slow waves. In this study we aim to
      distinguish and quantitatively reconstruct different slow wave patterns using an
      inverse algorithm. Slow wave patterns corresponding to normal, retrograde and
      uncoupled activity at different frequencies were imposed on a stomach surface
      model. Gaussian noise (10% peak-to-peak) was added to cutaneous potentials and
      the Greensite-Tikhonov inverse method was used to reconstruct the potentials on
      the stomach. The effectiveness of the number or location of electrodes on the
      accuracy of the inverse solutions was investigated using four different electrode
      configurations. Results showed the reconstructed solutions were able to reliably
      distinguish the different slow wave patterns and waves with lower frequency were
      better correlated to the known solution than those with higher. The use of up to
      228 electrodes improved the accuracy of the inverse solutions. However, the use
      of 120 electrodes concentrated around the stomach was able to achieve similar
      results. The most efficient electrode configuration for our model involved 120
      electrodes with an inter-electrode distance of 32 mm.

PMID- 24137716
TI  - Dry electrodes for electrocardiography.
AB  - Patient biopotentials are usually measured with conventional disposable Ag/AgCl
      electrodes. These electrodes provide excellent signal quality but are irritating
      for long-term use. Skin preparation is usually required prior to the application
      of electrodes such as shaving and cleansing with alcohol. To overcome these
      difficulties, researchers and caregivers seek alternative electrodes that would
      be acceptable in clinical and research environments. Dry electrodes that operate
      without gel, adhesive or even skin preparation have been studied for many
      decades. They are used in research applications, but they have yet to achieve
      acceptance for medical use. So far, a complete comparison and evaluation of dry
      electrodes is not well described in the literature. This work compares dry
      electrodes for biomedical use and physiological research, and reviews some novel
      systems developed for cardiac monitoring. Lastly, the paper provides suggestions
      to develop a dry-electrode-based system for mobile and long-term cardiac
      monitoring applications.

PMID- 24137717
TI  - Rare zoonoses in the USA.

PMID- 24137718
TI  - [Commentary on "Mechanical recanalization in acute ischemic stroke"].

PMID- 24137719
TI  - [New bird flu in China].

PMID- 24137720
TI  - Immune responses in the host-environment interface - understanding the mechanisms
      of allergic sensitization.

PMID- 24137721
TI  - Randomized controlled trials: why choose a superiority non-inferiority or
      equivalence study design? A priori form of study comparison: superiority, non
      inferiority, or equivalence.

PMID- 24137722
TI  - First drug to improve heart failure mortality in over a decade: coenzyme Q10
      decreases all-cause mortality by half in randomized double blind trial.

PMID- 24137723
TI  - Conquering incivility.

PMID- 24137724
TI  - How to reduce clabsis.

PMID- 24137725
TI  - Retraction notice to: Histone H2B ubquitination regulates retinoic acid signaling
      through the cooperation of ASXL1 and BAP1.

PMID- 24137727
TI  - Reflections: neurology and the humanities: a sheep in wolf 's clothing: a medical
      student among neurosurgeons.

PMID- 24137726
TI  - Retraction notice to: GAMT, a p53-inducible modulator of apoptosis, is critical
      for the adaptive response to nutrient stress.

PMID- 24137728
TI  - Author Response.

PMID- 24137729
TI  - Linking Clostridium difficile infection with depression.

PMID- 24137730
TI  - Rotavirus vaccine proves effective in newborns.

PMID- 24137731
TI  - Report indicates influenza vaccine programs should target the young.

PMID- 24137732
TI  - New vaccine against TB meningitis potentially appropriate for the
      immunocompromised.

PMID- 24137733
TI  - In response.

PMID- 24137734
TI  - Thoughts on the DSM-5.

PMID- 24137735
TI  - Linking conceptual mechanisms and transcriptomic evidence of plasticity-driven
      diversification.
AB  - The East African cichlid fishes provide text book examples of adaptive radiation.
      Diversification and speciation of cichlids associate with variation in diet and
      trophic morphologies among other ecological, behavioural and morphological
      phenotypes (Kocher 2004). Numerous case studies in cichlids reveal a role of
      developmental plasticity in generating jaw ecomorphs in response to variation in
      feeding ecology that can facilitate niche exploitation and subsequent
      diversification (e.g. Meyer 1987). Specifically, genetic divergence among such
      environmentally induced morphs can occur via reproductive isolation due to
      divergence in habitat and resource use in combination with genetic assimilation
      of environmentally induced phenotypes (West-Eberhard 2003; Pfennig et al. 2010).
      Expansion of this conceptual model has been hampered in part by the limited
      knowledge of the molecular mechanisms of plasticity in nonstandard model systems
      and the associated lack of evidence linking the molecular mechanisms of
      plasticity to those that generate phenotypic divergence among populations and
      taxa. In this issue of Molecular Ecology, Gunter et al. (2013) identify the
      transcriptional mechanisms of diet-induced lower pharyngeal jaw (LPJ) plasticity
      in the cichlid fish Astatoreochromis alluaudi. Natural populations of A. alluaudi
      exhibit variation in jaw morphology in relation to diet hardness. Among the
      plastic responses to diet are adjustments to the LPJ ranging from a robust
      molariform morph in response to a hard diet to a more gracile papilliform morph
      in response to a soft diet (Fig. 1). Gunter and colleagues induced developmental
      plasticity of the A. alluaudi jaw using diet manipulations and compared LPJ
      transcriptomic profiles of the resulting morphs. In this foundational work, the
      authors identify 187 differentially expressed genes that underlie the development
      and maintenance of diet-induced LPJ morphologies. This list includes a wide range
      of genes spanning from broad-acting transcription factors to signalling molecules
      and structural genes. Here, I examine the ontogeny of the molecular response to
      mechanical strain imposed by diet hardness and discuss the role of the stages of
      this response in the evolution of plasticity and plasticity-driven
      diversification.

PMID- 24137736
TI  - Reply to Mahowald and Gibson and to Heggarty: No problems with short words, and
      no evidence provided.

PMID- 24137737
TI  - A journey into the wild of the cnidarian model system Aiptasia and its symbionts.
AB  - The existence of coral reef ecosystems relies critically on the mutualistic
      relationship between calcifying cnidarians and photosynthetic, dinoflagellate
      endosymbionts in the genus Symbiodinium. Reef-corals have declined globally due
      to anthropogenic stressors, for example, rising sea-surface temperatures and
      pollution that often disrupt these symbiotic relationships (known as coral
      bleaching), exacerbating mass mortality and the spread of disease. This threatens
      one of the most biodiverse marine ecosystems providing habitats to millions of
      species and supporting an estimated 500 million people globally (Hoegh-Guldberg
      et al. 2007). Our understanding of cnidarian-dinoflagellate symbioses has
      improved notably with the recent application of genomic and transcriptomic tools
      (e.g. Voolstra et al. 2009; Bayer et al. 2012; Davy et al. 2012), but a model
      system that allows for easy manipulation in a laboratory environment is needed to
      decipher underlying cellular mechanisms important to the functioning of these
      symbioses. To this end, the sea anemone Aiptasia, otherwise known as a 'pest' to
      aquarium hobbyists, is emerging as such a model system (Schoenberg & Trench 1980;
      Sunagawa et al. 2009; Lehnert et al. 2012). Aiptasia is easy to grow in culture
      and, in contrast to its stony relatives, can be maintained aposymbiotically (i.e.
      dinoflagellate free) with regular feeding. However, we lack basic information on
      the natural distribution and genetic diversity of these anemones and their
      endosymbiotic dinoflagellates. These data are essential for placing the
      significance of this model system into an ecological context. In this issue of
      Molecular Ecology, Thornhill et al. (2013) are the first to present genetic
      evidence on the global distribution, diversity and population structure of
      Aiptasia and its associated Symbiodinium spp. By integrating analyses of the host
      and symbiont, this research concludes that the current Aitpasia taxonomy probably
      needs revision and that two distinct Aiptasia lineages are prevalent that have
      probably been spread through human activity. One lineage engages in a specific
      symbiosis with Symbiodinium minutum throughout the tropics, whereas a second,
      local Aiptasia sp. population in Florida appears more flexible in partnering with
      more than one symbiont. The existence of symbiont-specific and symbiont-flexible
      Aiptasia lineages can greatly complement laboratory-based experiments looking
      into mechanisms of symbiont selectivity. In a broader context, the study by
      Thornhill et al. (2013) should inspire more studies to target the natural
      environment of model systems in a global context targeting all participating
      member species when establishing ecological and genetic baselines.

PMID- 24137738
TI  - Current world literature. Skin allergy.

PMID- 24137739
TI  - Current world literature. Eye allergy.

PMID- 24137740
TI  - Reply to the letter to the editor by H Chabrol.

PMID- 24137741
TI  - Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain
      diseases. Study first to use 'structural' approach in hunt for amyloid-inhibiting
      agents.

PMID- 24137742
TI  - Key molecular pathways leading to Alzheimer's identified. Research approach
      highlights potential therapeutic targets.

PMID- 24137743
TI  - Path of plaque buildup in brain shows promise as early biomarker for Alzheimer's
      disease. Relatively early accumulation of plaques in temporal lobe was associated
      with cognitive decline.

PMID- 24137744
TI  - Penn study shows vascular link in Alzheimer's disease with cognition. Presence of
      vascular disease reported across different neurodegenerative diseases.

PMID- 24137745
TI  - Women suffer higher rates of decline in aging and Alzheimer's disease.

PMID- 24137746
TI  - Brain's 'garbage truck' may hold key to treating Alzheimer's and other disorders.

PMID- 24137747
TI  - A second amyloid may play a role in Alzheimer's disease, UC Davis researchers
      find.

PMID- 24137748
TI  - Alzheimer's disease protein controls movement in mice.

PMID- 24137749
TI  - "Traditional Medicine in the Era of HIV/AIDS in South Africa", International
      Convention Centre, Durban, 28th to 30th July 2010.

PMID- 24137750
TI  - Ocean science: Follow the fish.

PMID- 24137751
TI  - A new familial infantile form of diffuse brain-sclerosis.

PMID- 24137752
TI  - The SYCL toolkit: creating a program within a professional organization for young
      scientists.

PMID- 24137753
TI  - Mind how you go.

PMID- 24137754
TI  - Closed question.

PMID- 24137755
TI  - Two authors reply.

PMID- 24137756
TI  - Three authors reply.

PMID- 24137757
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24137758
TI  - The future of the Medicare home health program.

PMID- 24137759
TI  - Plasma cell leukemia masquerading as carcinocythemia.

PMID- 24137760
TI  - Platelet phagocytosis by neutrophils.

PMID- 24137761
TI  - Vitamin D deficiency in patients with erythropoietic protoporphyria.
AB  - BACKGROUND: The main symptom of patients with erythropoietic protoporphyria (EPP)
      is painful photosensitivity, starting within minutes of sun exposure and leading
      to sun-avoidance. As 80-100% of vitamin D is synthesized under the influence of
      sunlight, we investigated whether the avoidance of sunlight exposure in the Dutch
      EPP patient population causes vitamin D deficiency. Furthermore, we studied the
      relation between vitamin D levels, total erythrocyte protoporphyrin and quality
      of life. METHODS: In a cross-sectional study of 48 Dutch EPP patients (mean age
      41.4 years; range 16-77; 23 male, 25 female), we assessed serum 25-hydroxyvitamin
      D (25(OH)D) levels between June and November 2007, as well as total erythrocyte
      protoporphyrin (TEP) levels and Dermatology Life Quality Index (DLQI) scores.
      RESULTS: Mean serum 25(OH)D was 66 nmol/L (range 18-140, quartiles 36, 87).
      Twenty-two patients (46%; 15 male, 7 female) were vitamin D deficient. There was
      a significant difference (p = 0.029) in mean serum 25(OH)D between female (mean
      75 nmol/L, range 18-140) and male patients (mean 55 nmol/L, range 18-115). The
      level of serum 25(OH)D showed a negative correlation with total erythrocyte
      protoporphyrin (TEP) (Pearson rank correlation (r(p)) = -0.337; p = 0.034). Serum
      25(OH)D was inversely associated with scores of the Dermatology Life Quality
      Index (DLQI) (Spearman's rho correlation (r(s)) = -0.486; p = 0.001).
      CONCLUSIONS: The prevalence of vitamin D deficiency is high in the Dutch EPP
      population, especially in male patients, and correlates with the severity of EPP.
      Screening for and treatment of vitamin D deficiency should therefore be
      implemented in the care of these patients.

PMID- 24137762
TI  - The screening of SLC6A8 deficiency among Estonian families with X-linked mental
      retardation.
AB  - The urinary creatine:creatinine (Cr:Crn) ratio was measured in males from 49
      families with a family history compatible with X-linked mental retardation (XLMR)
      in order to estimate the prevalence of SLC6A8 deficiency in Estonia. We
      identified 11 boys from 9 families with an increased urinary Cr:Crn ratio (18%).
      In three related boys, a hemizygous missense mutation (c.1271G>A; p.Gly424Asp)
      was identified. Their mother was heterozygous for the same mutation. Although
      many missense mutations have been described, the p.Gly424Asp mutation has not
      been previously reported. The clinical expression varied widely among affected
      males of this family. Patients 1 and 3 had relatively mild clinical expression
      (mild mental retardation (MR) and attention deficit disorder), but patient 2 had
      all typical clinical signs of SLC6A8 defect such as moderate MR, autistic
      features, expressive dysphasia and epilepsy. Among our patients, we saw
      significant problems in speech and language development combined with attention
      and behavioural difficulties. The number of false-positive biochemical results
      with increased urinary Cr:Crn ratio was higher (18%) in our study than in
      previous reports (1.8-10%). We therefore suggest that repeated biochemical
      testing should be performed before DNA sequencing analysis. Our study suggests
      that 2% (95% confidence limits: 0.05-11.1%) of this Estonian XLMR panel are due
      to mutations in the SLC6A8, which is similar to the prevalence reported in other
      populations. We therefore conclude that creatine transporter deficiency is a
      relatively common genetic disorder in males with sporadic or familiar MR and
      diagnostic screening of them should always include screening for SLC6A8
      deficiency.

PMID- 24137763
TI  - Sequence variants in four candidate genes (NIPSNAP1, GBAS, CHCHD1 and METT11D1)
      in patients with combined oxidative phosphorylation system deficiencies.
AB  - The oxidative phosphorylation (OXPHOS) system, comprising five enzyme complexes,
      is located in the inner membrane of mitochondria and is the final biochemical
      pathway in oxidative ATP production. Defects in this energy-generating system can
      cause a wide range of clinical symptoms; these diseases are often progressive and
      multisystemic. Numerous genes have been implicated in OXPHOS deficiencies and
      many mutations have been described. However, in a substantial number of patients
      with decreased enzyme activities of two or more OXPHOS complexes, no mutations in
      the mitochondrial DNA or in nuclear genes known to be involved in these disorders
      have been found. In this study, four nuclear candidate genes--NIPSNAP1, GBAS,
      CHCHD1 and METT11D1--were screened for mutations in 22 patients with a combined
      enzymatic deficiency of primarily the OXPHOS complexes I, III and IV to determine
      whether a mutation in one of these genes could explain the mitochondrial
      disorder. For each variant not yet reported as a polymorphism, 100 control
      samples were screened for the presence of the variant. This way we identified 14
      new polymorphisms and 2 presumably non-pathogenic mutations. No mutations were
      found that could explain the mitochondrial disorder in the patients investigated
      in this study. Therefore, the genetic defect in these patients must be located in
      other nuclear genes involved in mtDNA maintenance, transcription or translation,
      in import, processing or degradation of nuclear encoded mitochondrial proteins,
      or in assembly of the OXPHOS system.

PMID- 24137764
TI  - [Intacsintracorneal ring segments in keratoconus].
AB  - INTRODUCTION: The spectrum of stage-related therapy of keratoconus has been
      broadened through surgical implantation of intracorneal ring segments (INTACS) as
      a possible method of reducing irregular astigmatism, leading to a reduction of
      corneal grafts especially in young, working-aged patients with keratoconus. The
      purpose of the present study was to evaluate the preoperative and postoperative
      results of femtosecond laser-assisted implantation of INTACS in ectatic corneal
      diseases. PATIENTS AND METHODS: From August 2011 to January 2013, 20 eyes from 16
      patients with a clear cornea in the visual axis suffering from hard contact lens
      intolerance underwent surgery in the Homburg/Saar Keratoconus Center (HKC) by the
      same surgeon (MEH). Among these were 16 keratoconus eyes, 1 eye with pellucid
      marginal degeneration und 3 eyes with post-LASIK iatrogenic keratectasia. The
      insertion of the INTACS ring segments was achieved by a femtosecond laser
      assisted procedure that created a precise 360 degrees  tunnel at a depth of 80%
      of the corneal thickness (395.8 +/- 38.5 MUm) in the 6-7 mm zone.Results. At 6
      months follow-up mean uncorrected distance visual acuity improved from 0.07 +/-
      0.07 preoperatively to 0.6 +/- 0.26 postoperatively. Mean best-corrected distance
      visual acuity changed from 0.4 +/- 0.15 preoperatively to 0.9 +/- 0.29
      postoperatively. Mean sphere decreased from -7.6 +/- 6.1 dpt to -1.4 +/- 2.8 dpt.
      Astigmatism decreased from -6.0 +/- 2.8 dpt preoperatively to -4.3 +/- 2.0 dpt
      postoperatively. There was also a reduction in the mean flat K from 47.8 +/- 4.7
      dpt preoperatively to 44.2 +/- 5.0 dpt postoperatively and in mean steep K from
      51.9 +/- 5.0 dpt to 48.4 +/- 6.6 dpt. The central eccentricity index in the
      Pentacam was reduced to around 50%. Neither intraoperative nor postoperative
      complications (including non-responders) were observed. CONCLUSIONS: The
      femtosecond laser-assisted INTACS implantation provides a valid alternative to
      early keratoplasty for keratoconus patients with a clear central cornea and
      contact lens intolerance. It is a minimally invasive and reliable method for
      stage-related surgical management of keratoconus.

PMID- 24137765
TI  - Open access publication--the wider context.

PMID- 24137766
TI  - Footnote to 'Radiation-induced cataracts: the Health Protection Agency's response
      to the ICRP statement on tissue reactions and recommendation on the dose limit
      for the eye lens'.

PMID- 24137767
TI  - The Violence Against Women Research and Evaluation Program at the National
      Institute of Justice.

PMID- 24137768
TI  - Multifaceted impairments of impulsivity in cannabis users? A reply.

PMID- 24137769
TI  - Retaining well-fixed cementless stem in the treatment of infected hip
      arthroplasty--reply.

PMID- 24137770
TI  - Dr. Ludvigsson, et al reply.

PMID- 24137771
TI  - Dr. Petri, et al reply.

PMID- 24137772
TI  - Dr. Fitzcharles, et al reply.

PMID- 24137773
TI  - Platelet-rich plasma for knee osteoarthritis--authors' response.

PMID- 24137774
TI  - Author response.

PMID- 24137775
TI  - Microarteriovenous malformations. Response.

PMID- 24137776
TI  - Subarachnoid hemorrhage and outcome. Response.

PMID- 24137777
TI  - Temporal lobe arteriovenous malformations. Response.

PMID- 24137778
TI  - Niacin and statin intolerable for some people.

PMID- 24137779
TI  - Feasibility trial reports deployment of new device for TAVI in aortic
      insufficiency.

PMID- 24137780
TI  - Spetzler-Martin grade III arteriovenous malformations. Author reply.

PMID- 24137781
TI  - Severe traumatic brain injury. Author reply.

PMID- 24137782
TI  - Intracranial hemorrhage and left ventricular assist devices. Author reply.

PMID- 24137783
TI  - Cranial orthosis therapy. Response.

PMID- 24137784
TI  - Fibrolipoma. Reply.

PMID- 24137785
TI  - 'Defying providence': a salutary new look at the history of smallpox.

PMID- 24137786
TI  - [Chemoradiotherapy for advanced head and neck cancer - patient survival is more
      important than reduced toxicity].

PMID- 24137787
TI  - [Sudden hearing loss - intratympanic dexamethasone: injection or perfusion?].

PMID- 24137788
TI  - Tribute to Jon Driver.

PMID- 24137789
TI  - Response to Yablonsky's letter to the editor.

PMID- 24137790
TI  - [Comment on this case report].

PMID- 24137791
TI  - Burkitt's lymphoma of the breast metastatic to the ovary diagnosed during
      pregnancy.

PMID- 24137792
TI  - Maria I of Portugal: another royal psychiatric patient of Francis Willis.

PMID- 24137793
TI  - Transcriptome analysis of female reproductive tissues of Anastrepha obliqua and
      molecular evolution of eggshell proteins in the fraterculus group.
AB  - The investigation of cDNA libraries has been an important tool for the
      identification of new genes in nonmodel species such as the fruit flies from the
      Anastrepha fraterculus group. In the present study, we constructed a cDNA library
      from the female reproductive tissues of Anastrepha obliqua aiming to identify
      genes with high evolutionary rates. We sequenced 2304 clones obtained from the
      female reproductive tissues of A. obliqua flies. The expressed sequence tags
      generated a total of 816 unigenes which were classified into different protein
      classes. Among these,we identified chorionic and vitelline protein genes as being
      among the most highly expressed. We used unigene sequences to amplify a set of
      chorionic and vitelline genes, involved in the formation of the eggshell,in
      species of the fraterculus group. Four chorionic genes and two vitelline genes
      showed evidence of positive selection along the Anastrepha and/or Tephritidae
      lineage. The signal of selection detected for Vm26Aa was possibly generated by a
      gene duplication event. The rapid evolutionary rates indicate that these genes
      could serve as important markers in population and evolutionary studies, not only
      for species of this group, but possibly also for other Diptera.

PMID- 24137794
TI  - Somalia: a gathering storm?

PMID- 24137795
TI  - Medical students drawn to eastern Europe.

PMID- 24137797
TI  - Reply to Brook et al: No empirical evidence for human overkill of megafauna in
      Sahul.

PMID- 24137798
TI  - Reply to Osterburg et al.: To study human inflammatory diseases in humans.

PMID- 24137799
TI  - Neighborhood socioeconomic status and stroke mortality: Disentangling individual
      and area effects. Author reply.

PMID- 24137800
TI  - A dedication to Alfred L. Goldberg.

PMID- 24137802
TI  - Leather football helmets. Author reply.

PMID- 24137801
TI  - Design, synthesis and brain uptake of LAT1-targeted amino acid prodrugs of
      dopamine.
AB  - PURPOSE: Drug delivery to the brain is impeded by the blood-brain barrier (BBB).
      Here, we attempted to enhance the brain uptake of cationic dopamine by utilizing
      the large amino acid transporter 1 (LAT1) at the BBB by prodrug approach.
      METHODS: Three amino acid prodrugs of dopamine were synthesized and their prodrug
      properties were examined in vitro. Their LAT1-binding and BBB-permeation were
      studied using the in situ rat brain perfusion technique. The brain uptake after
      intravenous administration and the dopamine-releasing ability in the rat striatum
      after intraperitoneal administration were also determined for the most promising
      prodrug. RESULTS: All prodrugs underwent adequate cleavage in rat tissue
      homogenates. The prodrug with phenylalanine derivative as the promoiety had both
      higher affinity for LAT1 and better brain uptake properties than those with an
      alkyl amino acid - mimicking promoiety. The phenylalanine prodrug was taken up
      into the brain after intravenous injection but after intraperitoneal injection
      the prodrug did not elevate striatal dopamine concentrations above those achieved
      by corresponding L-dopa treatment. CONCLUSIONS: These results indicate that
      attachment of phenylalanine to a cationic drug via an amide bond from the meta
      position of its aromatic ring could be highly applicable in prodrug design for
      LAT1-mediated CNS-delivery of not only anionic but also cationic polar drugs.

PMID- 24137803
TI  - Cerebellar tonsil position and Chiari malformation. Author reply.

PMID- 24137804
TI  - [Patient blood management - fewer transfusions, lower costs].

PMID- 24137805
TI  - Perspectives on neuroscience and behavior.

PMID- 24137806
TI  - Tapping passion: the untold talents of wellness champions, ambassadors, and peer
      educators.

PMID- 24137807
TI  - The power and potential of peer support in workplace interventions.
AB  - This article reviews the scientific evidence regarding the effectiveness of
      social support in chronic condition and health management with a focus on how
      peer educators and wellness champions improve outcomes in worksite health
      promotion programs.

PMID- 24137808
TI  - Image of the month. Gastric volvulus: an endoscopic ultrasound find.

PMID- 24137809
TI  - Characterization of patients undergoing total hip arthroplasty in a real-world
      setting and pain-related medication prescriptions for management of postoperative
      pain.
AB  - This observational study characterized medication use in the immediate
      postoperative period among patients undergoing total hip arthroplasty (THA) at an
      academic medical center, and evaluated pain (0-10 numerical pain rating scale
      [NPRS]; 0 = no pain, 10 = worst pain that the patient can imagine), function
      (Harris Hip Score [HSS]and Lower Extremity Function Scale [LEFS]), and health
      related quality of life (SF-36). Study patients (N = 115; 59% female; average age
      61.3 +/- 12.0 years; mean BMI of 29.9 +/- 6.9 kg/m2) who underwent THA between
      September 1, 2008, and November 30, 2010, and met study inclusion criteria were
      drawn from the University of Utah Orthopedic Clinic database. The most common
      comorbidities in these patients were osteoarthritis, hypertension, and chronic
      back pain. The most frequently prescribed class of pain-related medications in
      the immediate postoperative period was opioids. The most common nonopioid
      medications were bupivacaine, celecoxib, and midazolam. Opioids and celecoxib
      continued to be commonly prescribed at discharge. Pain was improved at a 6-week
      follow-up (mean change -3.3 +/- 3.3 points), as were HSS and LEFS, with mean
      changes of 19.9 +/- 24.2 and 8.7 +/- 16.9 points (P < .01 for both),
      respectively. Although SF-36 scores were also improved, these scores were
      significantly lower relative to normative values for the US general population as
      well as relative to individuals having both osteoarthritis and hypertension.

PMID- 24137810
TI  - Author's response.

PMID- 24137811
TI  - Author's response.

PMID- 24137812
TI  - Pushing the envelope on cost/benefit analysis.

PMID- 24137813
TI  - More to the story. Interview by Kristie Nybo.

PMID- 24137814
TI  - Commercial Cdk1 antibodies recognize  the centrosomal protein Cep152.

PMID- 24137815
TI  - Knowledge about the endocrine disorders.

PMID- 24137816
TI  - [Young physicians fail the coming general practitioners].

PMID- 24137817
TI  - BSS misdiagnosed as ITP.

PMID- 24137819
TI  - Allowing for ethnic group in antenatal screening for Down's syndrome.

PMID- 24137818
TI  - Homozygous hemoglobin C disease.

PMID- 24137820
TI  - The evolution of nonclinical regulatory science: advanced therapy medicinal
      products as a paradigm.

PMID- 24137821
TI  - Authors' reply.

PMID- 24137822
TI  - The author response.

PMID- 24137823
TI  - Abstracts of the 30th Annual Scientific Meeting of the European Society for
      Magnetic Resonance in Medicine and Biology (ESMRMB). Toulouse, France. October 3
      5, 2013.

PMID- 24137824
TI  - The author response.

PMID- 24137825
TI  - In reply.

PMID- 24137826
TI  - Within this issue.

PMID- 24137827
TI  - Does the neurobiology of migraine make migraine patients "difficult"?

PMID- 24137828
TI  - Impact: Pack a punch.

PMID- 24137829
TI  - Mentoring in psychiatric mental health nursing.

PMID- 24137830
TI  - Psychiatric mental health nurses: what should we be "called" in the broad health
      care arena?

PMID- 24137831
TI  - Letter to the editor.

PMID- 24137832
TI  - Publishing: Open citations.

PMID- 24137833
TI  - Referencing: The reuse factor.

PMID- 24137834
TI  - The maze of impact metrics.

PMID- 24137835
TI  - High hopes.

PMID- 24137836
TI  - Searching for life.

PMID- 24137837
TI  - Adolescent and pediatric gynecology--quality of life and health: gynecologic
      problems ranging from the common to the rare.

PMID- 24137838
TI  - Current world literature. Urogynecology.

PMID- 24137839
TI  - Bloodstream infections and preventable dialysis deaths.

PMID- 24137840
TI  - Positive thinking.

PMID- 24137842
TI  - Fiddling while the world warms.

PMID- 24137841
TI  - Patient health causes substantial portion of geographic variation in Medicare
      costs.
AB  - Key findings. (1) Substantial geographic variation exists in Medicare costs, but
      to determine the source and extent of this variation requires proper accounting
      for population health differences. (2) While physician practice patterns likely
      affect Medicare geographic cost variations, population health explains at least
      75 to 85 percent of the variations-more than previously estimated. (3) Policy
      strategies should consider the magnitude of the impact of beneficiary health
      status on Medicare costs in order to address geographic variation.

PMID- 24137843
TI  - Climate in the classroom.

PMID- 24137844
TI  - Coyotes in the crosswalks? Fuggedaboutit!

PMID- 24137846
TI  - The perfect kelvin.

PMID- 24137845
TI  - Doing a world of good. Interview by Dina Fine Maron.

PMID- 24137847
TI  - The holey land.

PMID- 24137848
TI  - Taste-blind mice make tangled sperm.

PMID- 24137849
TI  - The great explicator.

PMID- 24137850
TI  - The liver transplant divide.

PMID- 24137851
TI  - Total recall.

PMID- 24137852
TI  - The pertussis parable.

PMID- 24137853
TI  - Edit your photos? Feed the meter.

PMID- 24137854
TI  - An ear to the big bang.

PMID- 24137855
TI  - Long live the humans.

PMID- 24137856
TI  - Who will bankroll the next big idea?

PMID- 24137857
TI  - The polyglot patent boom.

PMID- 24137858
TI  - Why can't Mexico make science pay off?

PMID- 24137859
TI  - Help for the child with autism.

PMID- 24137860
TI  - The data-driven society.

PMID- 24137861
TI  - How to build a robot octopus.

PMID- 24137862
TI  - Russia's new empire: nuclear power.

PMID- 24137863
TI  - When science doesn't support beliefs.

PMID- 24137864
TI  - Renewable energy's hidden costs.

PMID- 24137865
TI  - The Joint Commission announces 2014 National Patient Safety Goal.

PMID- 24137866
TI  - ACCEPTED: revised requirement for critical access hospitals.

PMID- 24137867
TI  - Revisions to requirements for ambulatory care organizations.

PMID- 24137868
TI  - Ensuring full compliance with the Life Safety Code. Tips on meeting recurring
      compliance issues.

PMID- 24137869
TI  - ERRATA: comprehensive stroke center chapter.

PMID- 24137870
TI  - New and revised requirements address emergency management oversight.

PMID- 24137871
TI  - UPDATE: revision to surgical site infection goal.

PMID- 24137872
TI  - Together, Joint Commission hospital requirements and Baldrige performance
      excellence criteria support quality and safety improvement efforts.

PMID- 24137873
TI  - REVISED: certification decision process.

PMID- 24137874
TI  - New conversations to foster collaboration.

PMID- 24137875
TI  - Health information exchange achieving coordinated care.

PMID- 24137876
TI  - Global lessons for U.S. healthcare leaders.

PMID- 24137877
TI  - Communication: 10 communication mistakes employees make and how to fix them.

PMID- 24137878
TI  - Career: Five tips for aligning a candidate's job expectations with reality.

PMID- 24137879
TI  - What drives an ethical culture? Providing incentives, celebrating good behavior
      go a long way.

PMID- 24137880
TI  - Improving the patient experience with an eICU. Telehealth helps provide round-the
      clock patient care.

PMID- 24137881
TI  - Going the distance for breast health. Mobile mammography allows more women to be
      screened, increases early detection.

PMID- 24137882
TI  - ACA payment changes for Medicare and Medicaid. Disproportionate share hospital
      cuts attract attention.

PMID- 24137883
TI  - Fellowship programs boost careers of all involved.

PMID- 24137884
TI  - Achieving stronger physician engagement. Steps CEOs and boards should take to
      understand and improve engagement.

PMID- 24137885
TI  - Preventing infection after hip and knee replacements. Simple practices improve
      care while reducing costs.

PMID- 24137886
TI  - In this together. Two "masters" of healthcare leadership share strategies to
      achieve physician alignment.

PMID- 24137887
TI  - CEO survey on hospital-physician integration.

PMID- 24137889
TI  - Ethical issues related to a reduction in force.

PMID- 24137890
TI  - Board certification in healthcare management.

PMID- 24137888
TI  - Engaging early careerists creatively. Chapter takes advantage of grant program to
      involve early careerists.

PMID- 24137891
TI  - [The future of life insurance].

PMID- 24137892
TI  - [Lone atrial fibrillation--relevance for medical underwriting].
AB  - Atrial fibrillation is a common and multifaceted cardiac arrhythmia. At present
      rhythm and rate control can be considered equal regarding morbidity and
      mortality. Following scientific findings in the past years new therapeutic
      strategies and treatment options were developed. Therefore, a decision must be
      made not only between rate and rhythm control but also between the different
      antithrombotic drug regimes. Oral thrombin and factor X inhibitors herald a new
      era in antithrombotic therapy. The lack of necessity for routine INR monitoring
      certainly constitutes one of the greatest advantages of these novel agents in
      everyday clinical practice. Pulmonary vein isolation is a catheter-based
      treatment option for atrial fibrillation enabling the cure of arrhythmias for
      many patients--despite the high rate of recurrence. Many of these new
      therapeutical options lack long-term findings and previous successes are to be
      regarded with certain prudence.

PMID- 24137893
TI  - [Aspects of post-tramatic stress disorder after a traffic acident].
AB  - Post-traumatic stress disorder (PTSD) occurs most frequently in the general
      population after traffic accidents and affects up to 15 % of those involved.
      Mental and physical comorbidity, preliminary damage or injury can herald the
      development of PTSD, but the scope of social support after the accident plays a
      crucial role in whether and to what extent potential PTSD develops. Against this
      background, preventive and injury reduction aspects of the interaction between
      insurance companies and their customers are conceivable, which could also
      positively affect health economic and aspects of job or customer satisfaction.

PMID- 24137894
TI  - [Complementary and alternative medicine in oncology].

PMID- 24137895
TI  - [Collaboration between occupational physicians and other specialists including
      insurance physicians].
AB  - Collaboration between various stakeholders is essential for a well-operating
      vocational rehabilitation process. Researchers have mentioned, among other
      players, insurance physicians, the curative sector and employers. In 2011 the WHO
      organised the congress "Connecting Health and Labour: What role for occupational
      health in primary care". The congress was also attended by representatives of the
      WONCA (World Organisations of Family Medicine). In general, everyone agreed that
      occupational health aspects should continue to be seen as an integral part of
      primary health care. However, it is not easy to find literature on this subject.
      For this reason we conducted a review. We searched for literature relating to
      collaboration with occupational physicians in Dutch, English and German between
      2001 and autumn 2011. Our attention focused on cooperation with specialists and
      insurance physicians. Therefore, we searched PUBMED using MeSH terms and made use
      of the database from the "Tijdschrift voor bedrijfs- en verzekeringsgeneeskunde
      (TBV) [Dutch Journal for Occupational - and Insurance Medicine]". We also checked
      the database from the "Deutsches Arzteblatt [German Medical Journal]" and made
      use of the online catalogue from THIEME - eJOURNALS. Last but not least, I used
      the online catalogue from the German paper "Arbeits -, Sozial -, Umweltmedizin
      [Occupational -, Social -, Milieu Medicine]". Additionally, we made use of the
      "snowball - method" to find relevant literature. We found many references to this
      subject. The Netherlands in particular has done a lot of research in this field.
      However, there is little research on the cooperation between occupational
      physicians and specialists; in particular insurance physicians. This is
      interesting, because several authors have mentioned its importance. However,
      cooperation with other specialists seems not to be the norm. Therefore,
      cooperation between curative physicians (specialists but also family doctors),
      insurance physicians and other stakeholders is essential and should be improved.
      In the future researchers should develop techniques, which help to improve
      collabora- tion. For example, Dutch investigators advocate the development of
      guidelines. There is agreement that collaboration between occupational physicians
      and some other specialists is important. In particular, collaboration between
      specialists in physical medicine has been investigated. Also, curative physicians
      and insurance physicians have an important role in disability management. So all
      stakeholders should work together more intensively. However, literature is
      difficult to find and not often part of international literature. This must
      change urgently.

PMID- 24137896
TI  - [Unnoticed remaining health disorders in child soldiers--personal account of such
      events in Germany during the total phase of the Second World War].

PMID- 24137897
TI  - [Internist Congress 2013: from organ to the system].

PMID- 24137898
TI  - [Surgeons and internists establish Task Force for Transplantation Medicine].

PMID- 24137899
TI  - [New immunological concepts in oncology].

PMID- 24137900
TI  - [Recent findings in ].

PMID- 24137902
TI  - [Modern concepts of the interdisciplinary treatment of chronic pain].

PMID- 24137901
TI  - [Nearly one third of suspected malpractice is valid].

PMID- 24137903
TI  - [Increase in life expectancy in HIV infection].

PMID- 24137904
TI  - [Medical Insurance Conference 2013 of the German Association of Insurance
      Science].

PMID- 24137905
TI  - [Diabetics with mental health problems need special care].

PMID- 24137906
TI  - [Endocrine disruptors: scientists warn of chemical substances in packaging, food
      and cosmetics].

PMID- 24137907
TI  - [Valproic acid during pregnancy lowers IQ in children].

PMID- 24137908
TI  - [Foramen ovale closure: no standard therapy after stroke].

PMID- 24137909
TI  - [Nurses have contributed significantly to the improvement of pain management].

PMID- 24137910
TI  - [Politicians speak before the election about their plans for nursing].

PMID- 24137911
TI  - ["Nursing care would be served with a statutory regulation" (interview by
      Christian Heinemeyer)].

PMID- 24137912
TI  - [Pain in persons with a mental disability. Finding the right door].

PMID- 24137913
TI  - [Pain and pain measurement in children and adolescents with a developmental
      disability. When children cannot talk about their pain].

PMID- 24137914
TI  - [The pain of chronic wounds. The worst pain is the dressing change].

PMID- 24137915
TI  - [Complementary pain therapy. An extremely complex symptom].

PMID- 24137916
TI  - [Pain and immobility in long-term geriatric nursing. Preventing contraindicated
      rest].

PMID- 24137917
TI  - [Incontinence--a common issue for people with Parkinson's disease. A systematic
      literature review].
AB  - Parkinson's disease is among the most common neurological diseases. About 4.1
      million people are attected worldwide. The course of Parkinson's disease is
      chronically progressive. With L-Dopa therapy the life expectancy of people being
      affected by Parkinon's disease is not shortened compared with people who are not
      affected. Therefore people with Parkinson's disease often suffer from the serious
      effects for decades which include motor symptoms as well as vegetative
      disturbance, which concerns bladder function and functions of the
      gastrointestinal tract. Urinary and fecal incontinence involve severe impairment
      of quality of life. In this review the occurence of urinary and fecal
      incontinence should be determined in order to be able to describe its extent.
      There are different measures for treatment or improvement. These are reviewed
      based on the following research question: Which effects do interventions have in
      improving urinary and fecal incontinence in persons with Parkinson's disease
      compared to usual care? In order to answer the questions a systematic review was
      conducted. The literature search occured in the electronic databases Cochrane
      database, PubMed and CINAHL. Three studies investigating the prevalence with a
      total sample size of n = 1077 and for the evaluation of interventions four
      studies with a total sample size of n = 48 have been included. 25 percent of the
      women with Parkinson's disease suffer from urgency incontinence compared to seven
      percent of the women without Parkinson's disease (p < 0.01). Among men with
      Parkison's disease 28 percent are affected and six percent among men without
      Parkinson's disease (p < 0.01). In respect to stress and fecal incontinence there
      were no significant differences between people affected and people not affected
      by Parkinson's disease. With pelvic floor muscle exercises and accompanying
      measures as well as with injections of botulinum toxin A a reduction of urinary
      incontinence seems to be possible. Due to methodological insufficiency of these
      studies, no clear recommendations can be given.

PMID- 24137919
TI  - [Validity and reliability of the pain questionnaire "Brief Pain Inventory". A
      literature research].
AB  - BACKGROUND: Every fifth person in Europe suffers from chronic pain (Breivik et
      al. 2006). This number shows the topicality of this subject. For a professional
      and individual care of patients with chronic pain, it is essential to record the
      pain with a suitable and validated assessment instrument. AIM: Review of the
      validity and reliability of the pain questionnaire "Brief Pain Inventory" (BPI),
      and the applicability of BPI on adults with chronic pain in the acute hospital.
      RESEARCH QUESTION: Which statements can be made regarding the validity and
      reliability of the assessment instrument "Brief Pain Inventory" which is used in
      acute hospitals to assess chronic pain in adults who are capable of providing
      information about themselves? METHOD: A systematic literature research in the
      electronic databases Pubmed, Cochrane, Cinahl, Health Source, PsycInfo, Saphir
      and Web of Science. RESULTS: The original version and the slighty modified
      versions of the BPI show good to excellent validity and reliability. This
      instrument is adapted to measure malignant and nonmalignant chronic pain. It was
      used in pain and cancer clinics, in acute care hospitals, in family practices and
      in surveys. DISCUSSION: It is difficult to make a generally valid and
      scientifically based statement because different researchers have worked with
      different versions of the BPI, various groups of patients with different
      diagnoses and in diverse settings. CONCLUSIONS: The systematic literature review
      demonstrates the scientific part of evidence-based nursing, EBN. That means, from
      a scientific point of view, the BPI is suitable for detecting chronic pain in the
      acute hospital in adults who are capable of providing information about
      themselves. Further research about the different BPI modifications, the different
      types of pain, the use of the instrument in practice and a few quality criteria
      is recommended.

PMID- 24137920
TI  - [Performance of personality-oriented nursing II: Memory of experiences, expertise
      and quality of life. Forming a new configuration].

PMID- 24137921
TI  - [Evidence based management in health and social care. The logic behind
      decisions].

PMID- 24137922
TI  - [The first Prussian nursing textbook 1909. A standard for decades].

PMID- 24137923
TI  - [Literature research and literature review for nurses. Searching, viewing,
      evaluating].

PMID- 24137924
TI  - [In the spotlight: heart failure. Dyspnea, fatigue, edema].

PMID- 24137925
TI  - [Managing chronic pain. More than just a warning sign].

PMID- 24137926
TI  - [Methodological and organizational bases for the early rehabilitation of the
      patients under conditions of a multidisciplinary clinic].
AB  - The Federal Medical and Rehabilitation Center of the Russian Health Ministry
      Health is a unique therapeutic and prophylactic setting. Its unique character is
      attributable to the fact that it incorporates specialized clinical departments
      that provide high-tech medical care and the Center for Restorative Medicine and
      Rehabilitation. Collaboration of these units permits to initiate rehabilitative
      measures from the very first day of the patient's stay in the hospital with due
      regard for the nosological form of his (her) disease. The activities of the
      Center for Restorative Medicine and Rehabilitation are based on the application
      of up-to-date remediation technologies that ensure the long-term rehabilitative
      effect and allow the duration of hospital stay to be decreased. During many years
      of practical work, the Centre has developed the proper organizational structure
      and gained a vast experience of comprehensive early rehabilitation after the most
      common diseases that was summarized by its specialists in numerous publications
      and theses and was many times reported at various scientific forums in this
      country and abroad.

PMID- 24137927
TI  - [The early rehabilitation of the patients with shoulder impingement syndrome
      using robotic technologies].
AB  - The objective of the present study was to develop a complex of rehabilitative
      measures for the treatment of the patients presenting with shoulder impingement
      syndrome including the combined application of the robotic technology based on
      the Multi-Joint System (Italy) in conjunction with physical therapy and massage.
      In addition, we estimated dynamics of the "American assessment shoulder and elbow
      surgery" test, the shoulder score index, the range of motion in the shoulder
      joint on the affected side with the help of the Multi-Joint System. It is
      concluded that the early use of the Multi-Joint System in combination with
      physical therapy and massage techniques provides the highly efficacious tool for
      the management of the patients suffering impingement syndrome.

PMID- 24137928
TI  - [The application of the non-invasive lung ventilation technique (CPAP therapy)
      for the early comprehensive rehabilitation of the patients with metabolic
      syndrome and "night-piker" arterial hypertension].
AB  - The treatment of patients presenting with metabolic syndrome and "night-piker"
      arterial hypertension is a most difficult task facing modern therapy. It was
      shown that metabolic disorders and night-time elevation of arterial pressure in
      such patients are attributable to obstructive sleep apnea syndrome (OSAS). The
      present study included 32 patients suffering moderately severe or severe OSAS in
      conjunction with metabolic syndrome, and "night-piker" arterial hypertension. We
      tried to elucidate the role of CPAP therapy in the treatment and early
      rehabilitation of such patients. The study group included 17 patients and the
      control group was comprised of 15 subjects. The quality of sleep significantly
      improved in all the patients (100%) during 4 weeks of CPAP therapy;
      simultaneously, normalization of hemodynamics (the absence of the morning rise in
      AP) was documented. The morning rise in AP (up to 140/80 mmHg at awakening)
      persisted in 9 (60%) control patients. The mean cholesterol level decreased by
      28.65% and 25.89% in the study and control groups respectively (p>0.1). (all
      patients in both groups were treated with statins). The level of C-reactive
      protein decreased more significantly in the study group compared with the control
      one (38.22% and 15.32% respectively; p<0.05). It is concluded that CPAP therapy
      produces beneficial effect in the patients with OSAS suffering hypertension
      during the night or early in the morning. CPAP therapy during 1 month did not
      have an appreciable effect on metabolic parameters. At the same time, long-term
      CPAP therapy promoted the reduction in the level of C-reactive protein known to
      be a predictor of cardiac complications.

PMID- 24137929
TI  - [The role of laser therapy in the combined rehabilitation of the patients
      presenting with abdominal adhesions].
AB  - This article presents a brief description of the applications low-level laser
      therapy as an instrument for the treatment and early rehabilitation of the
      patients presenting with abdominal adhesions at the stage of their hospital stay.
      The data obtained give reason to recommend laser therapy as a method for the
      treatment and earlier rehabilitation of the patients with abdominal adhesions.

PMID- 24137930
TI  - [Diagnostics and early rehabilitation of biomechanical gait abnormalities in the
      patients with cerebral hemiparesis].
AB  - The objective of the present study was to evaluate the effectiveness of various
      systems for the analysis of gait biomechanics during the early period of
      rehabilitation in the patients presenting with central hemiparesis. 30 patients
      with central hemiparesis were examined with the use of the "Raptor-12", motion
      capture system, "TRUST-M" gyroscopic system, "Balance Master platform, and
      "Diasled" tension registration system. The severity of paresis estimated based on
      the 6-score scale varied from 2 to 4.5 (mean 3.7 +/- 0.9), the Ashworth
      spasticity index was 1.1 +/- 1.2. The clinically significant phenomena (low
      goniogram amplitude, gate asymmetry etc.) responsible for the poor mobility (the
      Rivermead index below 13) were revealed during the analysis using "Raptor-12" and
      "TRUST-M". These abnormalities served as the targets for the rehabilitative
      treatment. The analysis of walking parameters on the "Balance Master" platform
      provided no clinically significant results. The "Diasled" data made it possible
      to evaluate the treatment-induced improvement in the patients' conditions but had
      no influence on decision-making as regards the choice of the rehabilitation
      strategy. The analysis of gait biomechanics with goniometry provides a basis for
      differential early rehabilitation of walking disorders in the patients suffering
      central hemoparesis.

PMID- 24137931
TI  - [Organization and methodology of early rehabilitation of the patients with
      cardioembolic stroke complicated by cardiac insufficiency].
AB  - The present work was focused on the safety and effectiveness of the combined
      rehabilitative treatment in the case of pre-acute and acute cardioembolic stroke
      in 45 patients with varying degree of cardiac decompensation. The study showed
      that the use of "passive" remediation, such as the postural treatment, breathing
      exercises, selective massage, neuromuscular electrical stimulation, is safe and
      can be recommended to the patients with stroke and cardiac decompensation of
      different severity (II and III FC of chronic cardiac insufficiency). The
      introduction of such active measures as verticalization into the program of
      comprehensive rehabilitation may cause decompensation of cardiac insufficiency.
      The rehabilitation strategy used in the present study improved performance and
      exercise tolerance in the majority of the patients. Moreover, it resulted in the
      significant reduction of the severity of stroke, improved the motor function, and
      increased functional independence of the patients.

PMID- 24137932
TI  - [Navigated transcranial magnetic stimulation as a method of early motor activity
      disorders rehabilitation after stroke].
AB  - The objective of the present study was to compare the safety and effectiveness of
      navigated and non-navigated rhythmic transcranial magnetic stimulation rTMS in
      the patients presenting with post-stroke hemiparesis. METHODS: Group 1 consisted
      of 31 patients with post-stroke hemiparesis treated by navigated rTMS. Thirty
      comparable patients treated without navigation were included in Group 2. The
      patients were examined 3.2 +/- 1.1 month after stroke. Their mean age was 42 +/-
      10.1 years. The average NIHSS score declined from 15.9 +/- 3.5 to 10.2 +/- 3.9 in
      Group 1 and from 15.8 +/- 3.0 to 13.1 +/- 3.4 in Group 2 (p=0.05). The Barthel
      index characterizing the degree of functional independence increased from 14.5 +/
      4.4 to 25.7 +/- 6.8 in Group 1 and from 14.3 +/- 4.2 to 18.1 +/- 5.9 in Group 2
      (p=0.07). Navigated rTMS should be preferred as a method for locomotor
      rehabilitation after stroke.

PMID- 24137933
TI  - [Comprehensive programs and evaluation of the efficacy of early postoperative
      rehabilitation in the patients following total endoprosthetics of the lower
      extremity joints].
AB  - A total of 562 patients completed the course of rehabilitative treatment in the
      early postoperative period after the total replacement of hip joints in the lower
      extremities. Early mobilization (the first walking experience within 3-4 hours
      after surgery) is not only possible, but is also associated with the lower levels
      of pain and anxiety. The analysis of X-ray images of the operated joints 12
      months after the replacement revealed no signs of mechanical loosening of the
      prosthetic components which gives evidence of the safety of early postoperative
      walking.

PMID- 24137934
TI  - [Peculiarities of early rehabilitation of mountain ski athletes after plastic
      reconstruction of anterior cruciate ligament].
AB  - The primary objective of the present study was to estimate the effectiveness of
      the new methods of physical rehabilitation for mountain ski athletes designed to
      optimize and accelerate restoration of their professional capabilities after
      arthroscopic plastic reconstruction of anterior cruciate ligament (ACL). This
      open controlled prospective study involved 26 alpine skiers aged from 18 to 25
      who were recruited into the regular follow up program based at our Centre during
      the last 3 years. The athletes proved able to start balance training on the
      Biodex platform 4 weeks earlier than with the use of the conventional approach.
      These exercises were supplemented by the training of speed endurance on the Speed
      Courte tensor platform and Sky Teck ski simulators. Control studies were carried
      out on the 16th and 24th weeks of the rehabilitation period. Their results were
      compared with the results shown by the same athletes before injury. It was found
      that the early introduction of exercises designed to normalize proprioception
      into the rehabilitative treatment allowed the injured mountain ski athletes to
      restore the strength of femoral muscles and specific professional skills by the
      4th month of the rehabilitation period. It is concluded that the combination of
      classical rehabilitative techniques with balance training, Speed Court training,
      and training on the alpine ski simulator makes it possible to begin special of
      alpine ski training on the snow 2 months earlier than with the use of
      conventkional methods.

PMID- 24137935
TI  - [The estimation of the effectiveness of early rehabilitation of the athletes
      practicing different sports after the knee injury with the use of specific
      simulators].
AB  - There are yet no optimal criteria to be applied in rehabilitative sports medicine
      for the estimation of the restoration of the athletes' physical conditions to
      enable them to return to their professional activities. The primary objective of
      the present study was to develop specific methods for the assessment of the
      physical performance of the athletes safe enough for the use at any stage of
      testing and sufficiently informative to give idea of the athlete's condition. To
      this effect, we compared the effectiveness of various testing procedures specific
      for different sports. We divided the athletes suffering injuries to the knee
      joint into two groups. The control group consisted of athletes that were tested
      by classical diagnostic methods employed in sports medicine. The study group was
      comprised of the athletes examined by the methods specific for a given sport. The
      effectiveness of diagnostic methods was estimated based on the calculation of the
      frequency of repeated injuries during two months after the athletes were
      permitted to resume training. Results. The study has demonstrated that specific
      methods designed for testing alpine skiers, hockey players, and football players
      are more specific and produce better results if used for the assessment of the
      athletes' physical conditions in combination with the conventional diagnostic
      tests. Such an approach makes it possible to decrease the number of repeated
      injuries.

PMID- 24137936
TI  - [The early comprehensive rehabilitation of the children with perinatal pathology
      of the craniovertebral region and cerebrospinal neurological symptoms].
AB  - This paper is designed to report the results of a clinical study of the children
      presenting with neurologic pathology for the detection of the most common
      concomitant craniovertebral disorders. In addition, the experience of application
      of the methods for comprehensive rehabilitation is presented with special
      reference to remedial exercises, manual therapy, massage, and other
      physiotherapeutic procedures. Positive experience with the application of
      orthopedic devices is described including the Shants collars and corsets as well
      as the observance of the specific orthopedic locomotor regimen. These combined
      measures are designed to enhance the quality of life of the patients, correct
      their neurologic symptoms, and improve the compromised academic performance.

PMID- 24137937
TI  - [Verticalization as a factor of early rehabilitation in the patients with a
      spinal cord injury].
AB  - The number of days from the spinal cord injury to rehabilitation of the victim
      has significantly decreased. It means that the rehabilitative treatment begins
      when the risk of secondary trophic lesions, cardiovascular and respiratory
      complications is especially high. Training with the use of a tilt-table equipped
      with the dynamic foot support is considered to be the highly effective method for
      the prevention or reduction of orthostatic hypotension, impaired ventilation, and
      pressure sores. This approach makes it possible to influence the patient's
      motivation for further recovery, decrease the duration of hospitalization in the
      intensive therapy ward, accelerate adaptation of the patients to the vertical
      posture, decrease hypotension and hypoxia, reduce to a minimum the occurrence of
      secondary neurologic disorders. Dynamic tilt-table training is considered to be a
      more effective modality for the adaptation of the patient to the vertical
      position than standing with the assistance of a simple table.

PMID- 24137938
TI  - [The concept of early ("fast track") rehabilitation in abdominal surgery].
AB  - The data of evidence-based medicine are used to illustrate the role of a
      multimodal analgesia and early enteral feeding in combined rehabilitation of the
      patients operated on abdominal organs.

PMID- 24137939
TI  - [The clinical views of the humanist doctor F.P. Haas (the first quarter of the
      XIXth century). On the occasion of the 200th anniversary of the publication of
      F.P. Haas' book "Ma visite aux Eaux d'Alexandre en 1809 et 1810" (M., 1811)].
AB  - This paper is devoted to the analysis of clinical principles of physician
      humanist F.P. Haas expounded in his book "Ma visite aux Eaux d'Alexandre en 1809
      at 1810" by F.P. Haas (M., 1811). The translation of this book into the Russian
      language gave an idea of the clinical views of the medical profession in this
      country in the beginning of the XIXth century (before the Patriotic War of 1812)
      including relationship between doctors and their patients and medical ethics.
      Haas proposed a well-substantiated therapeutic strategy with the use of mineral
      waters taking into consideration residual assimilative capacity of the patient's
      organism.

PMID- 24137940
TI  - [The XIII all-Russian scientific and practical conference "The problems and
      prospects of rehabilitation and balneology based at the Russian spa and health
      resort facilities"].

PMID- 24137941
TI  - [Therapeutic strategy for chronic myeloid leukemia: possibilities and prospects].
AB  - Over the past decade the clinical introduction of agents that directionally
      blocks the activity of BCR-ABL tumor tyrosine kinase (TK) has changed the
      prognosis of chronic myeloid leukemia. A significant malignant Ph'-positive clone
      inhibition and durable remissions have made it possible to increase overall and
      relapse-free survival. Due to their higher life expectancy, the number of
      patients is on the increase and their quality of life and working capacity remain
      good. According to the All-Russian Register of Chronic Myeloid Leukemia, there
      were more than 6500 cases in the Russian Federation in 2012. Of them, 93.1% were
      diagnosed with the chronic phase of the disease, 6.4 and 0.4% with its
      accelerated phase and blast crisis, respectively. Among the BCR-ABL TK inhibitors
      (TKI) registered in the Russian Federation and recommended for the treatment of
      chronic myeloid leukemia, there are 3 medications: imatinib, nilotinib, and
      dasatinib. The efficiency and safety of TKI therapy have been well studied. The
      most important principle of treatment is to permanently affect the Ph'-positive
      tumor cell clone by the long-term daily use of TKls. Regular cytogenetic and
      molecular genetic monitoring allows adequate estimation of the leukemic clone
      volume and it is essential in evaluating the therapeutic effectiveness. To choose
      a TKI for each specific patient with regard for its best tolerability and maximum
      efficiency permits individualized treatment. The prospect of therapy
      discontinuation can be discussed only in individual patients with a durable and
      stable complete molecular response and only within clinical trials.

PMID- 24137942
TI  - [Treatment of adult patients with acute promyelocytic leukemia according to the
      AIDA protocol].
AB  - AIM: To give the results of an investigation conducted at the Hematology Research
      Center (HRC), Ministry of Health of the Russian Federation (MHRF), to treat adult
      patients with acute promyelocytic leukemia (APL) according to the AIDA protocol
      elaborated by Spanish investigators. SUBJECTS AND METHODS: The investigation
      enrolled 33 patients diagnosed with APL verified by cytogenetic and molecular
      studies, who had been treated at the HRC, MHRF, in July 2009 to January 2012. The
      patients classified in the low-, intermediate-, and high-risk groups were 30,
      46.7; and 23.3%, respectively. The analysis was made in January 2013. RESULTS:
      The number of patients who achieved complete remission, as well as the mortality
      rates during remission induction were wholly comparable to those previously
      obtained when using the 7+3+ATRA protocol: 90.3 and 9.7%, respectively. One
      patient in remission died (3.6% mortality rate). The likelihood of recurrence in
      this investigation was high (21%), which was due to gross noncompliance with
      maintenance therapy. On examining the clearance of the malignant clone by FISH
      and polymerase chain reaction, a naturally chimeric transcript identified by a
      molecular study was statistically significantly more frequently revealed during
      postinduction therapy, which was associated with different sensitivity of the
      techniques. Comparison of changes in the disappearance of a chimeric marker for
      APL with the AIDA and 7+3+ARTA programs showed that the clearance of the
      malignant clone was much slower. CONCLUSION: The AIDA program is a highly
      effective treatment protocol for patients with APL.

PMID- 24137943
TI  - [Allogeneic hematopoietic stem cell transplantation for acute myeloblastic
      leukemia in first remission].
AB  - AIM: To evaluate the efficiency of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first
      remission depending on the regimens of conditioning, the source of a graft, and
      the characteristics of a donor and a recipient. SUBJECTS AND METHODS: In 66
      treated patients, including from partially HLA-mismatched relatives (n=4), the
      efficiency of allo-HSCT from related donors (n=26) and unrelated donors (n=40),
      were compared. According to cytogenetic findings, 7 (11%), 31 (47%), and 10 (15%)
      patients belonged to low-, intermediate-, and high-risk groups, respectively.
      RESULTS: Five-year overall survival (OS) and mortality associated with
      transplantation were 56 and 22% for allo-HSCT from related donors, 68 and 23% for
      that from HLA-matched donors, and 71 and 25% for that from partially HLA
      mismatched donors, respectively (p=0.8 and p=0.7). The relapse risk after allo
      HSCT from unrelated donors was significantly lower than after that from related
      donors (13 and 35%, respectively; p=0.8). Univariate analysis showed that the OS
      rates depended on the cytogenetic risk group (OS was 24 and 64% in the high- and
      intermediate-risk groups, respectively (p=0.027). The relapse risk in chronic
      graft-versus-host reaction (GVHR) and in grade 3 acute GVHR (p=0.01) was shown to
      be less than that in grades 1-2 acute GVHR (p=0.06). CONCLUSION: OS rates after
      allo-HSCT from related and unrelated donors were comparable and unrelated to the
      source of a graft, the regimen of conditioning, and other characteristics of a
      donor and a recipient.

PMID- 24137944
TI  - [Efficacy of donor lymphocyte infusion in patients after different types of
      allogeneic hematopoietic stem cell transplantation].
AB  - AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and
      treat recurrences in patients after different types of allogeneic hematopoietic
      stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: Data from 118
      patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched
      related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched
      unrelated donors (n=2), and haploidentical donors (n=24) were performed. The
      indications for DLI were underlying disease relapse (59 DLIs), resistant disease
      course (n=40), minimal residual disease (n=1 6), falling donor chimerism (n=1 5),
      and recurrence prevention (n=1 3). RESULTS: Therapy response was obtained after
      57 (44%) DLls. There were 36 (25%) and 30 (21%) cases of acute and chronic graft
      versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched
      donors, its performance in the periods of D+100 to one year after allo-HSCT, a
      donor chimerism level of over 90% at the moment of DLI, the administration of the
      initial DLI dose of below 1.10(6) CD3+/kg, and the development of chronic GVHR
      after DLI were associated with the highest rate of therapy responses. The overall
      survival rates of patients with DLI were significantly influenced by factors,
      such as DLI periods, donor chimerism levels at DLI, and the development of
      chronic CVHR after DLI. CONCLUSION: The choice of the optimal dose of cells, the
      periods of DLI and its preventive administration improve prognosis in patients
      after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA
      matching and the type of a donor. The development of chronic GVHR after DLI is
      associated with the highest rate of responses to DLI and higher survival rates.

PMID- 24137945
TI  - [Cytogenetic characteristics of hematopoietic and stromal progenitor cells in
      myelodysplastic syndrome].
AB  - AIM: To study and compare cytogenetic abnormalities in the bone marrow (BM) and
      peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM
      mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS).
      Subjects and methods. The results of a cytogenetic analysis of the total
      population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and
      PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS
      transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors.
      Cytogenetic examinations were performed by G-banding of chromosomes and
      fluorescence in situ hybridization (FISH). RESULTS: The BMC karyotype was
      abnormal in 17 (49%) of the 35 patients (13 with MDS and 4 with AML); the others
      were found to have a normal BM karyotype. The FISH analysis confirmed the same
      cytogenetic abnormalities in the BM and PB CD34+ hematopoietic progenitor cells
      in all the examinees with an abnormal karyotype. The mean abnormal clone sizes in
      the total population of BMCs and BM and PB CD34+ progenitor cells did not differ
      and constituted 65.8, 73.1, and 74.8%, respectively. The patients with a normal
      BM karyotype had no chromosome abnormalities in the CD34+ cells either. The
      karyotype of MSCs was analyzed in 23 (19 with MDS and 4 with AML) of the 35
      patients. No karyotype abnormalities were revealed in the patients with MDS
      transformed into AML. There were structural chromosome aberrations in 2 (11%) of
      the 19 patients with MDS (one with constitutional inv(9)(p1 3q21) was found to
      have non-clonal translocation t(2;22)(p10;q1 1) and the other had a clone with an
      additional segment of the long arm of chromosome 2 in 35% of the cells. No
      numerical MSC karyotype abnormalities were detected. A normal MSC karyotype was
      defined in 7 healthy BM donors. CONCLUSION: The cytogenetic analysis of
      hematopoietic and mesenchymal progenitor cells showed that the chromosome
      abnormalities revealed in these cell populations were different in the patients
      with MDS. The isolated CD34+ cells displayed the same cytogenetic abnormalities
      as in a total population of BMC. Examination of the latter could reveal no
      cytogenetic abnormalities in the majority of the patients. A normal BMC karyotype
      was detectable in the patients with AML. Two (11%) patients with MDS were found
      to have structural chromosome abnormalities that differed from those detected in
      the total population of BMC and in isolated CD34+ cells. The differences of
      chromosome abnormalities in the hematopoietic and mesenchymal progenitor cells
      point to the fact that the stromal microenvironment is not part of the abnormal
      clone in MDS, however, it may be of great importance in the pathogenesis of the
      disease.

PMID- 24137946
TI  - [Cytogenetic profile in patients with primary myelodysplastic syndrome].
AB  - AIM: To analyze the prevalence of chromosome aberrations presented in the revised
      International Prognostic Scoring System (R-IPSS) in patients with de novo
      myelodysplastic syndrome (MDS). Subjects and methods. Chromosome aberrations were
      analyzed in 197 patients aged 14 to 86 years (median age 64 years) with de novo
      MDS. RESULTS: Karyotype abnormalities were revealed in 129 (65.5%) patients with
      de novo MDS. According to the IPSS criteria, the karyotypes found 52 (26.4%)
      patients were assigned to an intermediate prognostic group whereas in accordance
      with the R-IPSS guidelines, an intermediate karyotype group included chromosome
      abnormalities in 32 (16.2%) patients. Out of 5 R-IPSS prognostic types, the
      favorable karyotype group was the largest (48.2%). The very favorable and
      unfavorable karyotype groups comprised few patients with MDS: 3 and 3.6%,
      respectively. Despite the fact that it was not mentioned in the R-IPSS, a
      monosomal karyotype was verified in 24 (12.2%) patients There was a correlation
      of the (normal and complex) karyotype with bone marrow blast counts (r=0.469;
      p=0.000), but not with age. CONCLUSION: A variety of cytogenetic damages cannot
      identify the prognostic potential of all chromosome aberrations occurring in
      patients with MDS even if prognostic factors increased up to 5.

PMID- 24137947
TI  - [Eight-year experience in treating aggressive mediastinal large B-cell
      lymphomas].
AB  - AIM: To make a differential diagnosis of diffuse large B-cell lymphoma (DLBCL)
      with primary involvement of the mediastinal lymph nodes (LN) and primary
      mediastinal large B-cell lymphoma (PMLBCL); to evaluate the efficiency of a
      modified NHL-BFM-90 (M-NHL-BFM-90) program in the treatment of the above
      nosological entities. SUBJECTS AND METHODS: The investigation enrolled 60
      patients with large B-cell lymphoma (LBCL) with primary involvement of
      mediastinal LN who had been treated at the Hematology Research Center, Ministry
      of Health of Russia, in 2004 to 2012. The diagnosis of PMLBCL and DLBCL with
      primary involvement of mediastinal LN was based on histological findings, the
      phenotype of tumor cells, and molecular evidence. Treatment was performed
      according to the M-NHL-BFM-90 program. Three pregnant women received predelivery
      polychemotherapy (PCT) according to the VACOP-B protocol and continued to have a
      DexaBEAM chemotherapy regimen 3-4 weeks postpartum. In case of a residual mass,
      all the patients underwent consolidation radiotherapy to the mediastinal area in
      a total focal dose of 36 Gy. RESULTS: The diagnosis of PMLBCL was established in
      39 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30
      years); DLBCL with primary involvement of mediastinal LN was verified in 21
      patients: 8 men and 13 women whose age was 21 to 70 years (median age 30 years).
      After m-NHL-BFM-90 treatment protocol, 5-year overall survival rates in the
      patients with DLBCL with primary involvement of mediastinal LN and in those with
      PMLBCL were 95+/-5 and 86+/-6% and 5-year event-free survival rates were 95+/-5
      and 78+/-7%, respectively. All the pregnant women diagnosed with PMLBCL who had
      received the VACOP-B --> delivery--> Dexa-BEAM PCT regimen during pregnancy
      achieved remission. The follow-up periods were 30, 36, and 42 weeks. CONCLUSION:
      The patients with new-onset LBCL and primary involvement of mediastinal LN are a
      heterogeneous group that includes patients having two different diagnoses: PMLBCL
      and DLBCL. The efficiency of high-dose PCT is different in the patients with
      DLBCL with primary involvement of mediastinal LN and in those with PMLBCL (in
      spite of their similar clinical features, similar epidemiological
      characteristics, and the presence of the same unfavorable prognostic factors at
      onset).

PMID- 24137948
TI  - [Evaluation of tumor vascularization and microenvironment in follicular
      lymphoma].
AB  - AIM: To characterize the degree of follicular lymphoma (FL) vascularization and
      microenvironment by immunohistochemical studies (IHCS) of lymph node biopsy
      paraffin-embedded sections in 2 different disease pattern groups. SUBJECTS AND
      METHODS: The investigation included 59 patients: 39 (67%) women and 20 (33%) men
      whose age was 27 to 83 years (median age 53 years) treated at the Hematology
      Research Center, Ministry of Health of the Russian Federation (n=49), and the
      N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
      (n=10), in April 2001 to May 2011. In accordance with the clinical features of
      the disease, the authors identified 2 patient groups: 1) 31 patients with the
      good results of FL treatment and 2) 28 patients with its poor results. IHCS was
      performed on lymph node tumor biopsy paraffin-embedded sections prior to
      treatment using antibodies to CD34, D2-40, CD68, and granzyme B. Morphometric
      analysis was made applying microscopy and a Leica x400 digital camera. The images
      of histological specimens were processed by the computer program VideoTesT
      Morphology 5.2: the specific vessel area (%) in relation with tumor tissue was
      estimated under visual guidance of an investigator. Cytotoxic lymphocytes (CTL)
      and macrophages were quantitatively characterized using 1 mm2 of tumor tissue (12
      fields of vision with the objective lens magnifying x400). Immunohistochemical
      specimens to be examined were chosen randomly, by using the random number table.
      RESULTS: In Group 2, the specific area of blood vessels was statistically
      significantly higher than in Group 1: 0.04% (95% confidence interval (CI), 0.03
      to 0.05%) versus 0.02% (95% CI, 0.01 to 0.03%; p=0.05). In Group 2, that of
      lymphatic vessels was significantly higher than in Group 1: 0.06% (95% CI, 0.04
      to 0.07%) versus 0.03% (95% CI, 0.01 to 4%; p=0.03). With a nodular diffuse
      growth, Group 2 showed a significantly more CD68-positive macrophages than did
      Group 1: 800 (95% CI, 380 to 1222) versus 79 (95% CI, 10 to 566; p=0.01). In
      Group 1, the count of CTL was statistically significantly (p=0.05) higher than in
      Group 2 in both the nodule (with a nodular growth pattern: 14 (5-27) versus 5 (1
      11)) and the internodular space (with a nodular growth pattern: 158 (118-410)
      versus 35 (5-287) and with a nodular diffuse growth pattern: 126 (102-360) versus
      35 (3-120)). CONCLUSION: Increased tumor vascularization (estimated by the
      specific density of tumor vasculature) and a pronounced macrophageal reaction are
      associated with the poor outcomes of FL; the marked cytotoxic component in tumor
      tissue is linked to the favorable outcomes of the disease.

PMID- 24137949
TI  - [Morphological evaluation of dysmyelopoiesis in decitabine-treated patients with
      myelodysplastic syndromes].
AB  - AIM: To estimate a change in myelodysplasia in decitabine-treated patients with
      myelodysplastic syndromes (MDS). SUBJECTS AND METHODS: Thirteen MDS patients from
      a high-risk group were examined; 75 bone marrow puncture specimens and 67 bone
      marrow trepanobiopsy specimens from these patients were analyzed before and after
      decitabine treatment. Dysplastic changes in the hematopoietic cells were
      monitored during the treatment. RESULTS: The dysplastic changes in the
      hematopoietic cells are a morphological portrayal of the ineffective
      hematopoiesis in patients with MDS. The study has indicated that the use of the
      hypomethylating agent decitabine promotes the restoration of cell differentiation
      to mature forms, causing hematopoiesis to be more effective. The incidence of
      myelodysplasias (including mixed double- and triple-lineage ones) was
      statistically significantly reduced by decitabine treatment, which was associated
      with a positive response to treatment as a whole. The count of cells with
      dysplastic features remained unchanged in patients with therapy resistance or
      further disease progression. CONCLUSION: Analysis of myelodysplastic
      manifestations in different hematopoietic lineages in patients with MDS should be
      based on the comprehensive dynamic assessment of cytological and histological
      parameters at both the primary diagnosis of the disease and different stages of
      treatment. With a response to decitabine therapy (as shown by the results of
      aspiration and trepanobiopsy), all cell lines displayed reduced myelodysplastic
      changes, indirectly indicating a decrease of the abnormal clone itself in high
      risk MDS patients.

PMID- 24137950
TI  - [Characterization of the genotypes of patients with Gaucher disease type 1 in the
      Russian Federation].
AB  - AIM: To characterize the genotype and genotype-phenotype correlations in patients
      with Gaucher disease (GD) in the Russian Federation. MATERIALS AND METHODS: One
      hundred adult patients with GD type 1 were examined. Their clinical study
      encompassed the evaluation of the severity of osteoarticular lesions from
      instrumental findings. An allele-specific real-time polymerase chain reaction
      assay was used to screen four most common acid beta-glucoside gene (GBA)
      mutations (N370S, 84GG, L444P, IVS2+1). RESULTS: The N370S mutation and the
      N370S/? genotype where the second allele was presented with the mutation outside
      the 4 most common GBA gene mutations were found in the Russian patients with GD.
      Analysis of the clinical manifestations of the disease revealed no association
      between the genotype under examination and the severity of osteoarticular lesions
      and supported the unfavorable role of splenectomy (SE) in the development of
      severe bony disease. CONCLUSION: SE should be carried out in patients with
      unclear cytopenia and splenomegaly after the diagnosis of GD is excluded. The GD
      patients undergoing SE should receive emergency enzyme replacement therapy to
      prevent severe osteoarticular lesions and an irreversible orthopedic defect.

PMID- 24137951
TI  - [Successful use of vemurafenib in a patient with resistant hairy cell leukemia].
AB  - The paper describes a case of a patient with refractory hairy cell leukemia. In
      spite of the absence of CD25 expression, the disease was classified as a
      classical form according to the WHO classification (2008), as also confirmed by
      the detection of BRAFV600E mutation. The disease was characterized by resistance
      to all lines of therapy (interferon-a, splenectomy, cladribin). Clinical and
      hematological remission was achieved within 2 months of administration of the
      BRAF kinase inhibitor vemurafenib.

PMID- 24137952
TI  - [Successful therapy for enteropathy-associated peripheral T-cell lymphoma using
      high-dose polychemotherapy and autologous hematopoietic stem cell
      transplantation].
AB  - Enteropathy-associated T-cell lymphoma (EATL) is a rare disease that accounts for
      not more than 1.4% of all lymphomas. It is most common in Europe, followed by
      North America and Asia. The disease is associated with gluten-sensitive celiac
      disease in 50% of cases and divided into types I and II. Mean-dose CHOP-like
      therapy is ineffective, with a median overall survival of 7-10 months. With high
      dose therapy, 5-year survival rates can be 60%, but it can be used in not more
      than half of the cases. This is associated with the serious somatic status of
      most patients at diagnosis and with a median age of 57-64 years. The article
      presents a literature review and a case of successful therapy in a 58-year-old
      patient with type I EATL using the mNHL-BFM-90 protocol and autologous
      hematopoietic stem cell transplantation.

PMID- 24137953
TI  - [Multiple myeloma predominantly involving the spleen].
AB  - Extramedullary disease is an uncommon manifestation in multiple myeloma (MM) and
      can be observed at onset or develop at disease progression or relapse. Splenic
      involvement is very rare. The paper describes a 52-year-old female patient with
      MM who in 1990 was diagnosed with monoclonal gammopathy of undetermined
      significance with IgGkappa secretion and a considerably enlarged spleen. Specific
      therapy with bortezomib and dexamethasone was initiated in 2006 and proved to be
      inefficient. After splenectomy there was a 50% reduction in IgGkappa
      concentration. Splenic histological examination revealed monoclonal infiltration
      by the pleomorphic plasma cells expressing a kappa light chain.

PMID- 24137954
TI  - [Tuberculous sacroiliitis in a patient with Gaucher disease].
AB  - Gaucher disease (GD) is an inherited enzymatic defect resulting from a deficiency
      of acid [3-glucosidase, a lysosomal enzyme involved in the degradation of cell
      metabolic products. The major clinical manifestations of GD are
      hepatosplenomegaly, cytopenia, and bony involvement varying from asymptomatic
      osteopenia to severest osteoporosis and ischemic necrosis to develop irreversible
      orthopedic defects. Timely enzyme replacement therapy with recombinant
      glucosidase makes it possible to arrest disease progression and to prevent damage
      to the vital organs. However, GD in adult patients is frequently diagnosed in the
      presence of occurring osteoarticular lesions (arthrosis deformans, abnormal
      fractures). In these instances, besides enzyme replacement therapy, high-quality
      orthopedic care is required. The description of the case history of a patient
      undergoing splenectomy in childhood is given as a clinical example of severe
      osteoarticular lesion in GD and complex differential diagnosis with the
      intercurrent disease extrapulmonary tuberculosis.

PMID- 24137955
TI  - [Role of high-dose chemotherapy and autologous blood stem cell transplantation in
      patients with diffuse large B-cell lymphoma].
AB  - High-dose chemotherapy (HD-CT) in combination with autologous stem cell
      transplantation (auto-SCT) has long become the gold standard treatment for
      chemosensitive recurrences and refractory diffuse large B-cell lymphoma (DLBCL).
      By taking into account the low efficiency of rescue therapy (postrecurrence five
      year survival rate is not more than 10-20%), it is clear that the results of
      treatment should be improved in the induction of the first remission. The study
      performed in the rituximab time showed the higher efficiency of first-line
      therapy using auto-SCT. Therapeutic effectiveness was also noted to depend on the
      intensity of pretransplantation regimens. Indications for HD-CT with auto-SCT
      must be substantiated because of the higher toxicity together with therapy
      intensification. Conventional clinical criteria for this are insufficient. Thus,
      it is necessary to search for new molecular genetic prognostic factors that will
      be able to portray tumor biology.

PMID- 24137956
TI  - [Gene expression of vascular endothelial growth factors and their receptors in
      different variants of the course of multiple myeloma].
AB  - AIM: To determine the significance of the angiogenic activity estimated from the
      gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF
      C, and VEGF-D and their receptors VEGFR1, VEGFRls, VEGFR2, and VEGFR3 in the
      mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells
      predominating in different variants of the course of multiple myeloma (MM).
      MATERIALS AND METHODS: The gene expression of VEGF-A, VEGF-C, and VEGF-D and
      their receptors VEGFRI, VEGFRls, VEGFR2, and VEGFR3 was determined by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: VEGF-A, VEGF-C, VEGF
      D, as well as VEGFR1, VEGFRls, VEGFR2, and VEGFR3 were expressed showing
      different intensities in the mononuclear cell fraction of BM aspirates with a
      predominance of tumor plasma cells in the patients with MM, which allowed patient
      groups to be identified. In the group of high gene expression of VEGFs and their
      receptors, the number of clusters of plasma cells and vascular endothelium in the
      BM aspirates and the degree of osteolysis in the skeletal bones of patients with
      MM were significantly higher than those in the group of low or absent gene
      expression. The survival in the latter group was significantly higher.
      CONCLUSION: The investigation could provide an estimate of angiogenic processes
      in MM and establish their association with clinical manifestations and
      cytological characteristics.

PMID- 24137957
TI  - [Fundamental medicine as a basis of innovations in medical practice].

PMID- 24137958
TI  - [New clinical and organizational approaches to preventing cardiovascular diseases
      in the primary health care system].
AB  - The paper deals with the justification and description of clinical and
      organizational approaches to preventing cardiovascular diseases (CVD) in the
      primary health care system (PHCS) under the present conditions of health care
      modernization in Russia. It formulates the basic directions of systematic
      measures in integration strategies for the prevention of noncommunicable diseases
      (mainly CVD) at a federal level, in which practical measures are presented to
      improve a system for the early detection of high-risk individuals and to carry
      out measures for risk factor correction in PHCS, i.e. to implement high-risk
      strategies, including clinical and organizational approaches to reconstituting
      the medical prevention infrastructure in PHCS. This is favored by the new
      normative documents adopted by the Ministry of Health of Russia on the follow-up
      and prophylactic medical examinations of the adult population. The paper
      substantiates the objective need for such examinations and characterizes the main
      clinical and organizational approaches promoted in medical examinations, which is
      aimed at introducing the current science-based and economically expedient methods
      in the real practice of PHCS for the early identifications of atherosclerosis
      induced major CVDs and, what is particularly important, a risk for their
      development. Prophylactic counseling as a compulsory component is first being
      introduced in medical examination procedures. The key clinical and organizational
      principle of effective CVD prevention in public health is the implementation of
      the relationship and continuity of preventive measures, which becomes realistic
      with the adoption of new regulations of clinical examinations, prophylactic
      medical examinations, and follow-ups. The improvement of CVD prevention is
      associated not only with the introduction of organizational innovation changes,
      but also with the need to create a prevention ideology in physicians at all
      levels. It is emphasized that a comprehensive approach and all integrated CVD
      prevention strategies both at the population level and in the PHCS facilities are
      the most efficient and cost-effective procedure to reduce premature deaths from
      CVD in the population and to improve the demographic situation in our country.

PMID- 24137959
TI  - [Teaching therapeutic disciplines: vectors of modernization].
AB  - The paper discusses approaches to improving educational technologies in
      therapeutic disciplines taught at higher medical education institutes according
      to the basic curricula in Therapeutics (060101).

PMID- 24137960
TI  - [Pharmacotherapy for rheumatoid arthritis in the early 21st century: Russian and
      international experience].
AB  - The paper summarizes the data of international and Russian studies concerning
      current approaches to the pharmacotherapy of rheumatoid arthritis. Particular
      emphasis is placed on the substantiation of the treat-to-target concept, on the
      efficacy and safety of genetically engineered biological agents, including the
      inhibitors of tumor necrosis factor, interleukin-6 receptors, T-lymphocyte co
      stimulation, and anti-B-cell therapy.

PMID- 24137961
TI  - [Efficiency of treatment of adult patients with acute T-lymphoblastic leukemia
      according to the ALL-2009 protocol of the Russian Acute Leukemia Study Group].
AB  - AIM: To present the results of treatment in adult patients with acute T
      lymphoblastic leukemia (T-ALL) according to the ALL-2009 protocol of the Russian
      Acute Leukemia Study Group, the basic principle of which is continuation of
      cytostatic treatment, early switch from prednisolone to dexamethasone, and long
      term use of L-asparaginase. SUBJECTS AND METHODS: The results of diagnosis and
      treatment were analyzed in 70 patients with different immunological variants of T
      ALL treated in the Russian multicenter trial. RESULTS: Out of the 70 patients
      with T-ALL, its early immunotype was determined in 32 (45.7%) cases, the thymic
      and mature immunotypes were found in 31 (44.3%) and 7 (10%) cases, respectively.
      The median age of the patients with T-ALL was 28 (ranged from 15 to 54) years;
      men were twice more than women (48 and 22, respectively). Bone marrow lesion was
      noted in all the patients with early T-ALL and in 80% of the patients with thymic
      and mature T-ALL. The enlarged mediastinum was significantly more frequently
      detected in mature T-ALL (100%) than in its early (53.4%) and thymic (60.7%)
      variants. Therapeutic effectiveness was evaluated in 58 patients. An analysis was
      made in January 2013. Induction therapy resulted in complete remission in 49
      (84.5%) patients. The refractory course of the disease was recorded in 5 (8.6%)
      cases; early death was in 4 (6.9%). The rate of complete remission in thymic T
      ALL, unlike in the early (72%) and mature (71.4%) variants, was significantly
      higher (100%) due to the absence of resistant forms and early mortality.
      Moreover, it should be noted that only the patients with early T-ALL (16%) died
      during the induction phase. In the patients with different variants of T-ALL, the
      overall and relapse-free survival rates were not significantly different,
      accounting for 67.2 and 76.2%, respectively. Multivariate analysis revealed no
      prognostically unfavorable factors that determined long-term results. CONCLUSION:
      The ALL-2009 protocol is reproducible in any regions of the Russian Federation
      and highly efficient in treating patients with T-ALL.

PMID- 24137962
TI  - [Crohn's disease: on the occasion of the 80th anniversary of description].
AB  - In 1932, Burrill Bernard Crohn, Leon Ginzburg, and Gordon Oppenheimer published
      the paper "Regional ileitis: a pathological and clinical entity" first describing
      terminal ileitis that took further its name from B. Crohn. Crohn's disease (CD)
      is a recurring systemic inflammatory disease affecting the gastrointestinal tract
      (GIT) with extraintestinal manifestations and systemic immune disorders. Its
      etiology is unknown; the pathogenesis is associated with congenital impairments
      in the intestinal barrier and immune response to diversified symbiotic bacteria.
      The classification and the specific features of the natural history of CD are
      presented; the possibilities of new methods for its diagnosis and treatment are
      shown. Its new treatment goals are formulated; these are to achieve complete
      recovery of the involved bowel wall; to use confocal endoscopy, ultrasonography,
      magnetic resonance imaging, computed tomography, positron emission tomography,
      and the biomarkers C-reactive protein, fecal calprotectin, and lactoferritin.
      Algorithms for CD diagnosis and treatment using anticytokine agents and
      mesenchymal stromal stem cells are given.

PMID- 24137963
TI  - [Chronic obstructive pulmonary disease and comorbidities].
AB  - In current clinical practice, there are increasing numbers of patients in whom
      chronic obstructive disease is concurrent with three diseases: diabetes mellitus,
      coronary heart disease, and arterial hypertension. The concomitance of these
      socially significant diseases reflects a new stage of diseases of this century.

PMID- 24137964
TI  - [A combination of dipeptidyl peptidase-4 inhibitor and metformin in the treatment
      of patients with type 2 diabetes mellitus: effective control of glycemia, weight,
      and quantitative body composition].
AB  - AIM: To study the impact of intensified therapy with the dipeptidyl peptidase-4
      (DPP-4) inhibitor vilagliptin or sulfonylurea (SU) on the control of glycemia,
      weight, and quantitative body composition in patients with type 2 diabetes
      mellitus (DM-2) who have failed to achieve compensation during metformin
      monotherapy. SUBJECTS AND METHODS: Forty patients (mean age 55.0 (range 53.0
      60.7) years; disease duration 2.0 (range 1.1-5.0) years) with poor glycemic
      control (7%<HbA1c <10%) during metformin monotherapy were allocated to 2 groups
      for 6-month therapy. In group 1 (n=20), vildagliptin 100 mg/day was added to
      metformin; in Group 2 (n=20), the latter was added by SU with its dose
      adjustment. Dual-energy X-ray absorptiometry was used to quantify body
      composition at baseline and after 6 months. The efficiency of glycemic control
      and adiponectin level changes was evaluated at baseline and after 3 and 6 months.
      RESULTS: Following 6 months of treatment, both groups achieved a comparable
      reduction in HbA1c levels; however, the number of glycemic episodes during SU
      treatment was found to be significantly higher. When vildagliptin was used in
      combination therapy, with the lean body mass being preserved, there was a
      statistically significant decrease in total body weight, body mass index (BMI),
      fat mass, and tissue fat percentage without considering bone mass, as well as
      waist circumference (WC), which was attended by an elevation of adiponectin
      levels. On the contrary, when SU therapy was intensified, total body weight, fat
      mass, BMI, and WC were statistically significantly increased and adiponectin
      levels remained unchanged. CONCLUSION: The glucose-lowering efficiency of
      combination therapy with metformin + vildagliptin, a DPP-4 inhibitor, was
      comparable with that of a metformin + SU combination, but safer with respect to
      the risk of developing hypoglycemia. Addition of vildaglptin to metformin
      monotherapy may cause an additional favorable effect in reducing body weight at
      the expense of a fat component, with the lean body mass being preserved, and in
      elevating the level of adiponectin, an adipose tissue-derived antiatherogenic
      hormone.

PMID- 24137965
TI  - [Stepwise treatment in patients with isolated thermal inhalation injury].
AB  - AIM: To evaluate the efficiency of stepwise treatment in patients with isolated
      thermal inhalation injury (TIJ). SUBJECTS AND METHODS: The study enrolled 101
      patients with isolated TIJ. A study group (n=56) was treated at the Pulmonology
      Department after managing at the Burn Center (BC); a control group (n=45)
      received no systematic treatment after discharging from BC. The magnitude of
      respiratory symptoms (according to the rating system) and external respiratory
      function (ERF) was evaluated and fibrobronchoscopy was made in all the included
      patients at their discharge from BC. On admission to the Pulmonology Department,
      the study group patients underwent evaluation of the magnitude of respiratory
      symptoms, EFR, and lung diffusing capacity, determination of blood gas
      composition and exercise tolerance, and chest computed tomography. Respiratory
      symptoms, ERF, and exercise tolerance were evaluated in all the included patients
      one month after hospital discharge. RESULTS: Examination at the Pulmonology
      Department established preserved respiratory manifestations in patients who had
      to continue therapy. The use of beta2-agonists or inhaled steroids used in
      combination or alone need, mucoregulators or antibiotics revealed the efficiency
      of a stepwise approach to managing patients with TIJ. CONCLUSION: There is
      evidence that it is expedient to perform two-stage treatment in patients with
      TIJ, by transferring them from BC to a specialized pulmonology hospital, which
      substantially enhances the efficiency of medical care for this contingent of
      patients.

PMID- 24137966
TI  - [Extracorporeal photopheresis in the treatment of patients with refractory
      chronic graft-versus-host disease after allogeneic bone marrow transplantation].
AB  - AIM: To evaluate the efficiency of extracorporeal photopheresis (ECP) in the
      treatment of patients with refractory chronic graft-versus-host disease (cGVHD)
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS
      AND METHODS: The study included 49 patients aged 2 to 55 years. Allo-HSCT was
      carried out in 38 (79%) patients with acute leukemias, 5 (10%) with chronic
      leukemias, 4 (8%) with myelodysplastic syndrome/myeloproliferative disease, and 2
      (3%) with other hematologic diseases. The patients included in the study had
      glucocorticosteroid (GCS)-refractory disseminated cGVHD or a history of severe
      complications from GCS therapy. RESULTS: When evaluating the efficiency of
      therapy, its response was recorded in 37 (77%) cases; the best results were
      obtained in patients with hepatic (82%), mucosal (76%), and skin (74%) lesions.
      The mean severity according to the cGVHD Working Group, National Institutes of
      Health, and a platelet level of more than 100.10(9)/1 were defined as factors
      improving a therapy response. In the patients receiving ECP, the overall survival
      was 70%. The latter was higher in the group of patients who had responded to ECP
      therapy without involving the gastrointestinal tract in the cGVHD process and in
      those receiving a combination of ECP and other immunosuppressive drugs.
      CONCLUSION: ECP is an effective treatment for patients with refractory cGVHD, it
      may be used in those with a history of severe complications from GCS therapy. ECP
      allows the dose of GCS to be reduced to the point of complete discontinuation.

PMID- 24137967
TI  - [Role of splenectomy in the treatment of myelofibrosis].
AB  - AIM: To evaluate the clinical and hematologic efficiency of splenectomy (SE) in
      patients with myelofibrosis (MF) resistant to conventional traditional treatment.
      SUBJECTS AND METHODS: Case histories were retrospectively analyzed in 52 MF
      patients who had been followed up at the Hematology Research Center, Ministry of
      Health of the Russian Federation, in 2004 to 2012 and undergone therapeutic SE
      (47 patients with primary myelofibrosis, 4 with postpolycythemia myelofibrosis,
      and 1 with postthrombocythemia myelofibrosis). The mean age was 47 years at
      diagnosis and 53 years before surgery. The patients younger than 50 years of age
      constituted 60%. Massive and giant splenomegaly was detected in 37 (71%)
      patients. The spleen weighing 0.9 to 2.9 and 3 to 7 kg was removed in 15 (29%)
      and 35 (67%) patients, respectively. In 2 cases, the weight of the removed spleen
      was as much as 10 and 11 kg. RESULTS: By the moment of SE, the disease duration
      averaged 76 (from 1 to 240) months. Twenty-one (40%) patients developed
      perioperative complications, including bleeding (15%), thrombosis (11.5%), and
      infectious complications (13.5%). There were no deaths from surgical
      interventions in the intra- and early postoperative periods. In more than 80% of
      the patients after SE, their general condition improved and the symptoms of
      intoxication disappeared; in the majority of patients, the therapeutic effect
      lasted about 2 years. In the follow-up period, 33 (63%) patients died; the time
      to death averaged 27 (1-84) months following SE. The causes of death were blast
      transformation in 27 (82%) patients and comorbidity in 6 (18%); 19 (37%) patients
      with an average post-SE follow-up of 37 (4-72) months continued hydroxyurea
      treatment. The median survival after SE was equal to 3 years; the median overall
      survival was 11 years. CONCLUSION: SE is effective palliative care with an
      acceptable level of occurring complications for individual patients with MF.
      Contraindications to SE as blast crisis and severe comorbidities should be
      strictly taken into account.

PMID- 24137968
TI  - [Clinical efficiency of transfusion of pathogen-inactivated platelet
      concentrates].
AB  - AIM: To evaluate the effect of pathogen-inactivated platelet concentrates (PIPC)
      on posttransfusion platelet increments, hemorrhagic syndrome relief, and
      transfusion intervals. SUBJECTS AND METHODS: This prospective study included 29
      hemoblastosis patients (13 women, 16 men), median age 38 years (20-66 years).
      Pathogens were inactivated by the photodynamic method using the Intecept system.
      Each patient received two PC transfusions: one PIPC transfusion and one control
      one. Posttransfusion platelet increments one hour and one day after PC
      transfusion, the course of hemorrhagic syndrome, and the time to next platelet
      transfusion were analyzed. RESULTS: Pathogen inactivation with amotosalen and
      ultraviolet irradiation reduced posttransfusion platelet increments in recipients
      by 24% after one hour and by 29% after one day after PIPC transfusion versus
      control ones. CONCLUSION: The clinical efficiency of transfusions of amotosalen
      induced PIPC was comparable with that of untreated platelet concentrates. Despite
      a reduction in post-transfusion platelet increment with the use of PIPC, this
      caused no significant increase in the frequency of transfusions.

PMID- 24137969
TI  - [Prognostic value of a number of blood laboratory parameters in the use of
      erythropoiesis-stimulating agents in anemic patients with lymphoproliferative
      diseases].
AB  - AIM: To clarify the prognostic value of the baseline blood levels of endogenous
      erythropoietin (EE) and tumor necrosis factor-a (TNF-a) involved in the key
      components of the pathogenesis of anemia in lymphoproliferative diseases (LPD),
      the counts of reticulocytes and platelets (hematopoietic preservation indicators)
      in the use of erythropoiesis-stimulating agents (ESAs) to correct anemia syndrome
      (AS) in patients with LPD. SUBJECTS AND METHODS: The results of AS treatment with
      ESAs were analyzed in 48 patients with LPD. A study group comprised patients with
      chronic lymphocytic leukemia (n=1 3), indolent lymphomas (n=14), and multiple
      myeloma (n=21). Their hemograms (hemoglobin concentration, red blood cells,
      packed cell volume, reticulocytes, and platelets) and blood EE and TNF-alpha
      levels were examined before using ESAs. The hemogram was monitored during
      treatment. ESAs (eralfon (epoietin alpha) in 21 patients and epres in 27) were
      subcutaneously injected in a dose of 150 IU/kg thrice weekly (for not more than
      16 weeks). A control group included 21 anemic patients with multiple myeloma who
      did not receive ESAs. Increasing hemoglobin concentrations up to 120 g/l was
      regarded as a positive response to ESA treatment. RESULTS: By and large, the
      efficacy of epoietin alpha was 62.5% (61.9% for eralfon and 63.0% for epres),
      which was significantly higher than that in the control group (23.4%; p<0.05). A
      number of blood laboratory parameters were found to be of value in predicting the
      efficacy of ESAs. The patients with the decreased baseline concentrations o EE (
      <130 mlU/ml) and TNF- alfa (,15 pg/ml) were ascertained to show a positive
      response more frequently (80 and 92.9%, respectively; p<0.05) than those with
      thepredicting the efficacy of ESAs. The patients with the decreased baseline
      concentrations of EE (<130 mlU/ml) and TNF-a (<15 elevated concentrations of the
      enzymes in question. In addition, a positive response was more often recorded in
      patients with reticulocyte counts of more than 1% (77.4%; p<0.05) and platelets
      of 100-10(9)/1 (70%; p=0.05). CONCLUSION: Estimating the baseline blood levels of
      EE and TNF-a and the counts of reticulocytes and platelets prior to the use of
      ESAs enables prediction of the efficiency of erythropoiesis-stimulating therapy
      in anemic patients with LPD.

PMID- 24137970
TI  - [Neyromidin in the treatment of stage I hypertensive dyscirculatory
      encephalopathy].
AB  - AIM: To evaluate the efficacy and safety of neyromidin in the treatment of Stage
      I hypertensive dyscirculatory encephalopathy (HDE) and to analyze long-term
      treatment results. SUBJECTS AND METHODS: Fifty-seven with Stage I dyscirculatory
      encephalopathy in the presence of grades 1-2 arterial hypertension were examined.
      Clinical, psychological, and electrophysiological studies were performed and the
      efficacy of neyromidin was evaluated using the SANDOS geriatric scale. Neyromidin
      as monotherapy was used as one tablet (20 mg) b.i.d. during a meal. The duration
      of course treatment was 3 months. RESULTS: Positive changes in the early
      manifestations of HDE were observed just on day 45 of therapy. The therapeutic
      effect of the drug manifested as a reduction in the degree of clinical symptoms.
      There were positive changes in attention, memory, kinetics, verbal associations,
      counting. The most noticeable improvement was seen in the values of memory and
      intellectual processes, suggesting higher working capacity, reduced fatigability,
      and eliminated sluggishness of intellectual processes. EEG displayed a higher
      amplitude level, a better response to rhythmic photostimulation, and a total
      power rise in a- and 8-ranges, which was indicative of the activated effect of
      neyromidin on the functional state of brain structures. CONCLUSION: Neyromidin
      (20 mg b.i.d. for 3 months) was shown to be effective and well tolerated. The
      drug reduced the magnitude of clinical manifestations and improved psychological
      functions and electrophysiological parameters.

PMID- 24137971
TI  - [The combined drug ascoril in the treatment of patients with chronic obstructive
      pulmonary disease concurrent with coronary heart disease].
AB  - AIM: To evaluate the clinical efficacy of the combined drug ascoril (Glenmark,
      India) in patients with grade I-Ii chronic obstructive pulmonary disease (COPD)
      concurrent with coronary heart disease (CHD). SUBJECTS AND METHODS: Sixty
      patients, including 12 (20%) women and 48 (80%) men, aged 43 to 68 years (mean
      age 55.1 +9.9 years), with COPD were examined. The patients were divided into 2
      groups. Group 1 used the combined broncholytic and expectorant drug ascoril and
      Group 2 took mucolytic agent ambroxol. The follow-up period was 7 days. RESULTS:
      On day 2 of ascoril treatment, all the patients showed a significant reduction in
      the intensity of cough that was completely relieved in 26 (87%) patients by
      treatment day 7. Prior to ascoril treatment, heart rate (HR) was 64.4+/-5.5
      beats/min. A significant increase in HR to 72.7+/-10.1 beats/min was observed 20
      min after the first drug intake (p < 0.05) and a decrease to 68.6+/-10.5
      beats/min was seen after 60 min. On treatment day 7, HR was 63.0+/-6.5 beats/min,
      which was similar to that before ascoril treatment (p = 0.6). CONCLUSION: In the
      patients with COPD concurrent with CHD, the combined drug ascoril exerts
      broncholytic and expectorant effects, with no pronounced negative action on HR.

PMID- 24137972
TI  - [Irritable bowel syndrome: the present view of the problem].
AB  - The paper gives an update on irritable bowel syndrome and reveals problems in its
      classification, pathogenesis, clinical picture, and differential diagnosis. It
      presents principles in the treatment of patients in the context of evidence-based
      medicine and proposes a treatment algorithm for the major types of irritable
      bowel syndrome.

PMID- 24137973
TI  - [Moscow therapeutic schools (from the 1920s to the 1940s)].
AB  - Six leading Moscow therapeutic schools in the 1920s to the 1940s are first
      identified and given in this paper; their personal composition, distinctive
      characteristics, and role in the history of Russian internal medicine are shown.

PMID- 24137974
TI  - [Peculiarities of ocular blood flow in ischemic optic neuropathy and normal
      tension glaucoma].
AB  - Characteristics of ocular hemodynamics in ischemic optic neuropathy (ION) outcome
      and normal tension glaucoma (NTG), the conditions that are difficult to be
      differentially diagnosed, have been investigated. The study enrolled 32 patients
      (40 eyes) with ION outcome, 26 patients (46 eyes) with NTG, and 20 patients (32
      eyes) with no ocular pathology. Besides the standard ophthalmological
      examination, color Doppler imaging of ocular vessels, evaluation of ocular blood
      flow volume and individual normal range of intraocular pressure (flowmetry) were
      performed in all cases. The results showed that an excess of the actual
      intraocular pressure (IOP) over the individual normal range was much higher in
      patients with NTG than in patients with ION (39% and 14.5% correspondingly). It
      was also found that NTG is associated with a more significant decrease of ocular
      blood flow volume (30.1% in average) in comparison to ION outcome (11%). In both
      conditions a decrease in velocity parameters of the blood flow in main ocular
      vessels was registered, however, ocular hemodynamics changes appeared to be more
      severe in patients with glaucomatous optic neuropathy. A statistically reliable
      correlation between volumetric and velocity parameters of ocular blood flow has
      been discovered.

PMID- 24137975
TI  - [Potentialities of immunofluorescence in examination of retinal vascular system
      and epiretinal proliferation (experimental study)].
AB  - An immunofluorescent method of examination of retinal vascular system and
      epiretinal proliferative tissue removed during a transciliary surgery has been
      developed. The proposed method possesses certain advantages, i.e. high-quality
      visualization of the vascular system in total mounts, particularly, of the
      capillary loops and fine vascular terminals, the possibility to use specific
      immunohistochemical markers to identify all kinds of present cells (glia,
      endothelium, neurons) and evaluate their proliferative activity.

PMID- 24137976
TI  - [Results of regional ocular hemodynamics examination in patients with vitreous
      hemorrhage].
AB  - 150 patients were examined to study ocular hemodynamics in vitreous hemorrhage.
      64 patients had diabetes mellitus associated vitreous hemorrhage and 86 patients
      had hypertension background. Besides routine ophthalmological examination color
      Doppler mapping of ocular vessels and evaluation of hemorrhage volume and
      acoustic density in 3D mode were performed. Hence hemorrhage volume was found to
      have correlation with diastolic blood flow velocity in central retinal artery
      (CRA), systolic and diastolic blood flow velocities in CRA were showed to be
      reduced in vitreous hemorrhage.

PMID- 24137977
TI  - [Level of tear endothelin-1 and plasminogen in patients with glaucoma and
      proliferative diabetic retinopathy].
AB  - A considerable tear endothelin-1 increase (2-3 times) has been found in patients
      with primary open-angle glaucoma and proliferative diabetic retinopathy. Patients
      with proliferative retinopathy also showed an increase of plasminogen level in
      tear fluid and a tendency of a similar increase in blood serum. No correlation
      between endothelin-1 and plasminogen levels in these pathologies was established.
      Tear endothelin-1 and plasminogen measurement could be used as an informative and
      non-invasive method to help prognosis making, condition severity evaluation and
      control the effectiveness of treatment of ocular local microcirculatory
      disturbances.

PMID- 24137978
TI  - [Long-term results of transcorneal activation of the site of previous hypotensive
      surgery].
AB  - The goal of this report is to introduce a technique of transcorneal activation of
      the site of previous hypotensive surgery, its complications and long-term
      results. The study enrolled 100 patients aged from 39 to 84 who underwent a
      transcorneal activation procedure due to decompensation of intraocular pressure 2
      weeks - 20 years after the previous hypotensive surgery. Group I included 40
      patients after a nonpenetrating deep sclerectomy; group II consisted of 60
      patients after a penetrating hypotensive surgery. There were no intraoperative
      complications during the transcorneal activation procedure in both groups.
      Postoperative complications occurred in 5% of patients in group I (two
      ciliochoroidal detachments) and in 8.3% of patients in group II (three hyphemas
      and two ciliochoroidal detachments). In both groups a statistically reliable
      decrease of intraocular pressure comparing to preoperative values was present
      during the whole period of follow-up (up to 3 years) and averaged 34.6%.

PMID- 24137979
TI  - [Correlation between biomechanical properties of the corneoscleral tunic and
      stereometric parameters of the optic nerve head in congenital and acquired
      myopia].
AB  - The correlation between biomechanical properties of the corneoscleral tunic and
      stereometric parameters of the optic nerve head in children and adolescents with
      congenital and acquired myopia has been studied comparatively. The results showed
      that in children with high myopia, congenital or acquired, the corneoscleral
      parameters (scleral echodensity at the equator and the posterior pole,
      corneoscleral hysteresis, cornea resistance factor, and ocular rigidity
      coefficient) are lower than those in emmetropes. Moreover, the corneoscleral
      biomechanical characteristics affect the optic nerve head parameters. This fact
      has to be taken into account when examining adults with high myopia for the
      purpose of early diagnostics of glaucoma.

PMID- 24137980
TI  - [Regarding the method of the total tear production assessment].
AB  - Different Schirmer test I techniques presented in the literature have been
      reviewed and a comparative study of Schirmer test I results obtained with the
      eyes opened and closed has been conducted. The total tear production with the
      eyes opened vs. closed averaged 17.1+/-1.1 mm and 12-1.2 correspondingly
      (p=0.001; Mann-Whitney U test). In 22% of patients values were higher with the
      eyes closed rather than opened. The authors recommend to specify the conditions
      of the performed test when entering the results into the patient's chart.

PMID- 24137981
TI  - [Capabilities of physiotherapy for orbital trauma].
AB  - The article describes the results of conservative treatment of 78 patients with
      injuries of ocular adnexa (isolated fractures of orbital walls as well as
      cicatrical deformities of orbits and eyelids). Ophthalmological assessment was
      made both in the early and the late periods following blunt trauma. All patients
      underwent a standard assessment of functional ability of the eye and,
      additionally, an orbital computed tomography scan to characterize the fractures.
      In all cases physiotherapy (endonasal electrophoresis with proteolytic enzymes)
      was carried out to resolve the orbital hemorrhage. Binocular vision evaluation
      was done to control the effectiveness of the treatment. For that, the extent of
      diplopia in the central field and the total area of peripheral double vision were
      measured and the vertical edges of the diplopia zone were defined.

PMID- 24137982
TI  - [Impact of the method choice and the extent of correction on the development of
      visual evoked potentials in children and adolescents with refractive anomalies].
AB  - The article discusses a possible impact of different refraction correction
      methods, providing full or partial correction, on visual acuity and the
      development of visual evoked potentials in children and adolescents with myopia
      and myopic astigmatism. The accuracy of identification of visual evoked
      potentials depends, as shown in the article, on the extent of the correction
      chosen and the method used. In childhood the visual system is very susceptible to
      visual afferent deficit. The permanent deficit of visual information impedes
      further maturation of the visual analyzer, i.e. the development of central
      vision, binocular vision, and stereopsis. In high myopia it is important to
      decide not only on the extent of the correction but also on the method to use. In
      patients wearing soft contact lenses the visual evoked potentials have more
      regular shape, amplitude, and latency. The introduction of silicone hydrogel and
      daily disposal contact lenses, spherical and toric (for astigmatism correction),
      provided an opportunity to solve hygienic problems associated with contact lens
      use in children and adolescents and to decrease the risk of hypoxia
      complications.

PMID- 24137983
TI  - [Features of the stress-induced immunoreactivity of the organism in dynamics of
      the clinical current of the burn disease of eyes].
AB  - The individual adrenergical immunological reactivity of the organism (IA IRO) was
      investigated in 142 patients with eye burn of various degree. 2 types of IA IRO
      have been allocated by level and orientation of T-adrenoreception dynamics
      changes.

PMID- 24137984
TI  - [Results of corneal and total astigmatism estimation by different methods in
      myopic patients wearing orthokeratology contact lenses].
AB  - Reports have been made that corneal aberrations of all orders, including
      astigmatism, often significantly increase with the use of night orthokeratology
      lenses. In this study the dynamic changes of total and corneal astigmatism in
      myopes using orthokeratology lenses was evaluated by different methods. The study
      enrolled 38 patients (76 eyes) with low and medium myopia (28 and 48 eyes
      correspondingly) and initial astigmatism less than 2 diopters. The assessment was
      made before and in different terms after the patient started to wear
      orthokeratology lenses. Induced astigmatism (> or =1 diopter) was found in more
      than 50% of cases. The degree of astigmatism gradually increased from the centre
      to the periphery within the papillary zone. The maximum values were found within
      a 4-mm zone ("uptake zone") and minimal - within a 8-mm zone ("equalization
      zone"). In all patients, despite the presence of induced astigmatism and residual
      myopia (0.83+/-0.09 diopters in average), distance visual acuity was high enough
      without an additional correction (0.82+/-0.05 in average). Apparently, in these
      patients the aberrations (astigmatism in particular) exceed the focal depth.

PMID- 24137985
TI  - [Peculiarities of intraocular lens power calculation in infants under 1 year of
      age with congenital cataract].
AB  - The study enrolled 76 infants under 1 year of age (120 eyes) who underwent a
      total of 837 complex ophthalmological assessments, including ultrasound biometry
      and automatic refractometry. The assessment consisted of keratometry performed
      prior to cataract surgery, ultrasound biometry before and in different terms
      after the surgery, and evaluation of refraction in pseudophakic eyes. The power
      of intraocular lenses to be installed was determined using the principle of
      undercorrection. The follow-up periods ranged from 1 to 4 years. In 3.5-4.0 years
      after the surgery developmentally normal refraction was present in 58.5% of
      cases. According to analysis of refractive errors, the undercorrection prescribed
      to infants with preexisting II degree axial microphthalmia should be 2-3
      diopters.

PMID- 24137986
TI  - [Modern views of causes of microvascular complications development and
      progression in type 2 diabetes mellitus and peculiarities of their treatment].
AB  - Numerous independent studies conducted over the last decade have proved that
      impaired lipid metabolism is the predominant risk factor for vascular lesions of
      the fundus in patients with type 2 diabetes mellitus. The changes in lipid
      metabolism are called "the atherogenic triad of diabetes", or the metabolic
      syndrome, and include an increase of triglyceride level and percentage of
      especially atherogenic low-density lipoproteins, along with a decrease of
      percentage of high-density lipoproteins. Fenofibrate influences the
      microcirculation of patients with type 2 diabetes via normalization of mentioned
      parameters, thus reducing the intensity of metabolic syndrome. Moreover,
      fenofibrate has a non-lipid pleiotropic effect which positively influences the
      microvascular system even in case of a normal lipid profile. Medical treatment
      with fenofibrate harmoniously complements the results of retinal laser
      photocoagulation due to its antiapoptotic, anti-inflammatory, and antioxidant
      action as well as a decreasing effect on vascular reactivity.

PMID- 24137987
TI  - [Molecular genetic aspects of glaucoma pathogenesis].
AB  - To improve our understanding of glaucoma pathophysiology it is important to
      investigate endophenotypes which are determined by heritable quantitative traits,
      such as intraocular pressure, vertical cup-to-disc ratio, optic disc area, and
      central corneal thickness. Glaucoma is associated with increased intraocular
      pressure and defects of trabecular meshwork and anterior chamber which lead to
      derangement of intraocular fluid outflow, progressive optic nerve degeneration,
      loss of nerve cells, and blindness. Factors that are not affected by intraocular
      pressure also contribute to glaucoma degeneration. In progressive degenerative
      diseases, such as glaucoma, chronic astrocyte activation exacerbates the damage
      to neurons and impairs the regeneration of their axons. This review considers the
      polymorphism of predisposition factors to glaucoma-associated endophenotypes,
      optic nerve degeneration, and side effects of antiglaucomatous drugs.

PMID- 24137988
TI  - [Medication assisted activation of unveoscleral outflow of intraocular fluid in
      glaucoma: pathogenic aspects].
AB  - The article provides an overview of the main groups of IOP-lowering drugs which
      activate uveoscleral outflow in glaucoma and this activation is a key component
      of mechanism of action of these drugs. The issues related to the change of tone
      of ciliary muscle and its participation in uveoscleral outflow, and also
      relationship of accommodation and aqueous flow in glaucoma pathogenesis and
      possible pharmacological effects of these processes are being discussed.

PMID- 24137989
TI  - [Regarding the so called posterior approach for posterior eye wall foreign body
      removal].
AB  - Disadvantages of the posterior approach for the optic nerve head foreign body
      removal, especially with associated intraocular hemorrhage, have been analyzed.
      In such circumstances the transvitreal approach is of an evident benefit since it
      also allows removing the intraocular hemorrhage which is a potential source of
      severe vitreoretinal proliferation.

PMID- 24137990
TI  - [Regarding the discussion on the article of V.V. Volkov, namely a comment in the
      context of the discussion].

PMID- 24137991
TI  - Keeping one's cool when things hot up.
AB  - Hospitals and healthcare facilities use a variety of heating, ventilation, and
      air-conditioning (HVAC) equipment for a wide range of applications. Here, in our
      latest technical guidance article, presented in a 'Question and Answer'-type
      format, Adam Spolnik, director, and Richard Metcalfe, sales director, of
      temperature control specialist, ICS Cool Energy, focus on some of the key
      priorities, maintenance-wise, to get the optimum performance from chillers and
      HVAC components, and identify the units that perform best for particular
      healthcare applications. They also consider how careful stewardship and proper
      maintenance of such equipment can help cut carbon footprint, and highlight some
      of the key regulations that estates teams operating such plant need to ensure
      they are familiar with.

PMID- 24137992
TI  - Flexible 'zoning' aids adaptability.
AB  - Simon Corben, business development director at Capita Symonds' Health team,
      examines how 'clever use of zoning' when planning new healthcare facilities could
      improve hospital design, increase inherent flexibility, and reduce lifetime
      costs, and argues that a 'loose-fit, non-bespoke approach' to space planning will
      lead to 'more flexible buildings that are suitable for conversion to alternative
      uses'.

PMID- 24137993
TI  - Planning schemes to minimise disruption.

PMID- 24137994
TI  - Measuring best value from 'refurb' projects.
AB  - Research at Aberdeen's Robert Gordon University has identified the requirement
      for the development of a 'Decision Support Model' to 'facilitate and measure the
      selection of main elements and sub-elements within refurbishment and maintenance
      projects'. One of the major drivers, explains Grant Wilson, a completing PhD
      researcher with the University's Institute for Innovation, Design and
      Sustainability (IDEAS), was to provide a mechanism via which NHS estates
      managers, design teams, and contractors, could 'evidence and demonstrate' that
      best value-for-money had been pursued, 'specific to the facility in question, and
      in the context of its unique business case requirements'.

PMID- 24137995
TI  - A practical approach to waste management.
AB  - In March 2013, the Department of Health (DH), in partnership with the Department
      for Environment, Food and Rural Affairs (DEFRA) and the Department of Transport,
      produced an updated version of Health Technical Memorandum 07-01 (HTM 07-01),
      fully supported by the Environment Agency (EA), the Health and Safety Executive
      (HSE), and the devolved administrations. Here, Stuart Budd, head of Environment,
      Safety and Health, and Keerti Baker, PR and communications executive, at SRCL,
      one of the UK's leading healthcare waste specialists, look in some detail at the
      updated guidance, with a particular focus on new developments in the area of
      clinical waste.

PMID- 24137996
TI  - Benefiting from a trail of destruction.
AB  - Data destruction and IT asset disposal are heavily regulated and complex areas,
      especially within the NHS, which is responsible for the safekeeping of extremely
      personal data on millions of UK citizens. In the light of escalating efforts by
      the Information Commissioner's Office (ICO) to ensure compliance with the Data
      Protection Act 1998, data destruction specialist, Julie Pickersgill, of Advanced
      Digital Dynamics, outlines the requirements on estates departments for the secure
      disposal of IT equipment - and how to avoid falling foul of the law.

PMID- 24137997
TI  - Dialysis unit's high quality supply.
AB  - Kalpesh Shah, Healthcare product manager - Renal, ELGA Process Water, explains
      how a water treatment and purification system installed by the company as part of
      the recent 19 m sterling pounds refurbishment of the Cossham Memorial Hospital in
      Bristol is providing a constant supply of Renal Association-compliant water to a
      new dialysis unit, and saving the facility's operator significant sums annually
      in the process.

PMID- 24137998
TI  - Hospital keeps cool and cuts its costs.
AB  - Energy usage--particularly electricity--in hospitals is a hot topic, and the
      sector is under increasing pressure to reduce load and carbon emissions. The cost
      of 'going green' can, however, be high, and many hospitals shy away from more
      costly energy-efficient solutions, instead selecting cheaper options to suit the
      short term. One Hampshire healthcare facility, however, bucked the trend when
      selecting new chilled water plant, thanks to the advice and expertise of
      chartered consulting engineers, Henderson Green. Examining whether other
      hospitals should follow suit, managing director, Russ Pitman, explains 'why
      considering the bigger picture perspective does pay off'.

PMID- 24137999
TI  - Copper--a weapon in the war on pathogens.
AB  - The bacteria responsible for healthcare-associated infections can survive for
      anything from days to weeks on the fabricated surfaces, typically made from
      stainless steel and polymeric materials, that surround patients in our hospitals.
      Here Angela Vessey, director of the Copper Development Association (CDA) in the
      UK, describes some of the latest evidence from installations and studies
      worldwide of how using anti-microbial copper for common hospital items and
      surfaces can help to reduce environmental contamination, and thus lower
      healthcare-acquired infection rates.

PMID- 24138000
TI  - Strengthening safety in the MRI room.
AB  - A new MRI and CT scanning unit at Winchester's Royal Hampshire County Hospital,
      run by the Hampshire Hospitals NHS Foundation Trust, has been officially opened
      by the city's MP, Steven Brine, having been completed in February by Brymor
      Contractors, under advice from TKL Architects, to replace a former imaging
      facility badly damaged by a fire in December 2011. As HEJ editor, Jonathan
      Baillie, reports, the new building features a head and whole body HD imaging CT
      scanner from GE, and a 1.5 T Philips Ingenia MRI scanner, as well as Ferroguard
      ferromagnetic detection equipment from Metrasens designed to 'screen' individuals
      about to enter the MRI scanning room for ferrous objects.

PMID- 24138001
TI  - Generating revenue from X-ray waste.
AB  - According to Betts Envirometal, experts in precious metal recovery from waste
      streams, and a provider of 'total waste management' solutions, 'disposing of
      hospital wastes isn't usually a glamorous subject, unless, of course, you know
      how to make money from it'. As general manager, Simon Hundal, explains, the
      company is seeking to 'revolutionise' how the NHS treats certain waste streams,
      and, in doing so, to encourage NHS Trust directors and governance managers to
      check their compliance with patient data retention guidelines as far as medical X
      ray film, in particular, is concerned.

PMID- 24138002
TI  - Heating systems to maximise efficiency.
AB  - Jeff House, marketing and applications manager, Baxi Commercial, identifies some
      of the heating options available to the operators of healthcare facilities, and
      highlights practical examples of successful applications.

PMID- 24138003
TI  - Water oxidation using a cobalt monolayer prepared by underpotential deposition.
AB  - Development of electrocatalysts for the conversion of water to dioxygen is
      important in a variety of chemical applications. Despite much research in this
      field, there are still several fundamental issues about the electrocatalysts that
      need to be resolved. Two such problems are that the catalyst mass loading on the
      electrode is subject to large uncertainties and the wetted surface area of the
      catalyst is often unknown and difficult to determine. To address these topics, a
      cobalt monolayer was prepared on a gold electrode by underpotential deposition
      and used to probe its efficiency for the oxidation of water. This electrocatalyst
      was characterized by atomic force microscopy, grazing-incidence X-ray
      diffraction, and X-ray photoelectron spectroscopy at various potentials to
      determine if changes occur on the surface during catalysis. An enhancement of
      current was observed upon addition of PO4(3-) ions, suggesting an effect from
      surface-bound ligands on the efficiency of water oxidation. At 500 mV
      overpotential, current densities of 0.20, 0.74, and 2.4 mA/cm(2) for gold,
      cobalt, and cobalt in PO4(3-) were observed. This approach thus provided
      electrocatalysts whose surface areas and activity can be accurately determined. 

PMID- 24138004
TI  - The end of DNA patents in the United States?
AB  - For over 20 years, the US Patent & Trademark Office (USPTO) has been granting
      patents to DNA sequences. But on 13 June 2013, the US Supreme Court decided that
      genomic DNA sequences are unpatentable because they are products of nature. This
      article discusses the effect that this will have on DNA patents in the Unites
      States and in other countries.

PMID- 24138005
TI  - The effect of platelet-derived microparticles in stored apheresis platelet
      concentrates on polymorphonuclear leucocyte respiratory burst.
AB  - BACKGROUND AND OBJECTIVES: Platelet-derived microparticles (PMPs) and other
      proinflammatory mediators, which are accumulated during the storage process,
      might induce transfusion adverse events. We hypothesized that the PMP primed
      polymorphonuclear neutrophil (PMN) respiratory burst after the transfusion, which
      could be linked to the transfusion-related acute lung injury (TRALI). MATERIALS
      AND METHODS: The PMPs were isolated by centrifugation of the platelet-free plasma
      from 10 apheresis platelet concentrates (A-PLTs) at 20,000*g for 1 h. The PMPs
      were counted by flow cytometric analysis, followed by Western blotting, that were
      performed on isolated PMPs. The soluble CD40 ligand (sCD40L, sCD154) was assayed
      with ELISA. The priming of the formyl-Met-Leu-Phe (fMLP)-activated PMN
      respiratory burst was measured with the hydrogen peroxide production. RESULTS:
      The PMP counts increased by 1.7-folds after 3 days of storage. Meanwhile, sCD40L
      also significantly increased in PMP fraction isolated from the 3-day stored A
      PLTs. Furthermore, Western blotting indicated that sCD40L was involved and
      concentrated in PMP. The PMPs were able to effectively prime the fMLP-activated
      PMN respiratory burst, which was partly inhibited by CD154 monoclonal antibody or
      by filtration with 0.1 MUM membrane. Significant relativity was existed between
      the PMP counts, sCD40L and priming activity during the A-PLT storage. CONCLUSION:
      The platelet-derived microparticles, which carried the sCD40L, accumulated in the
      apheresis platelet concentrates during the 5 days of storage. They primed the
      fMLP-activated PMN respiration burst, which might be relative to TRALI.

PMID- 24138006
TI  - Surface-dependent localized surface plasmon resonances in CuS nanodisks.
AB  - We demonstrated revertible shifts of surface-dependent localized surface plasmon
      resonances (LSPRs) in CuS nanodisks. Oleylamine (OYA) served as a solvent and
      surface ligand covering on CuS nanodisks during the thermolysis of single-source
      precursor copper ethylxanthate (Cu(ex)2). When OYA ligand was unloaded and
      reloaded on the surface of CuS nanodisks, the wavelength of LSPRs blue-shifted
      due to more oxygen exposure and then reverted through surface repassivation. The
      surface-dependent shift of LSPRs was dominated by the concentration of free holes
      in CuS nanodisks, which was modulated by the coverage and exchange of surface
      ligands, and the oxygen exposure dose and time. The semiconductor nanocrystals
      with tunable LSPRs have great potential in advanced plasmonics. 

PMID- 24138007
TI  - Self-assembled DNA hydrogel as switchable material for aptamer-based fluorescent
      detection of protein.
AB  - The methodology based on target-responsive structural switching is powerful in
      bioanalysis with the controllability and sensitivity. In this paper, an aptamer
      functionalized DNA hydrogel was designed as a specifically target-responsive
      switchable material for protein detection. This pure DNA hydrogel was constructed
      by using a Y-shaped DNA and an aptamer linker through a DNA self-assembly without
      synthetic polymer backbone. With use of thrombin as the model analyte, the DNA
      hydrogel was first applied to visual detection with the entrapped Au
      nanoparticles (AuNPs) as indicating agent. Furthermore, the positively charged
      quantum dots (QDs) as the fluorophore were synthesized by using polyethyleneimine
      (PEI) as wrapper and characterized with spectroscopy, transmission electron
      micrograph, zeta potential, and dynamic laser scattering techniques. Along with a
      gel-to-sol transition in the presence of the target, the released negatively
      charged AuNPs from the hydrogel could approach the positively charged QDs. Due to
      the electrostatic interaction, fluorescence resonance energy transfer between PEI
      QDs and AuNPs therefore occurred and quenched the fluorescence signal for the
      sensitive detection of thrombin. This assay for the detection of thrombin showed
      a good linear relationship in a range of 0.075 to 12.5 MUM with a detection limit
      of 67 nM at 3sigma, and demonstrated excellent feasibility in complex serum
      matrixes. The biocompatible DNA hydrogel provides a universal switchable material
      for signal transduction and significantly demonstrates proof-of-concept for the
      detection of proteins. 

PMID- 24138008
TI  - From the editor-in-chief's desk.

PMID- 24138009
TI  - Nutritional and safety outcomes from an open-label micronutrient intervention for
      pediatric bipolar spectrum disorders.
AB  - OBJECTIVE: The purpose of this study was to report the safety, tolerability, and
      serum micronutrient concentrations and their correlations with mood changes from
      an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement,
      EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD). METHODS: Ten
      children ages 6-12 received EMP+ escalating from one to four capsules t.i.d.,
      with four children increased to the maximum suggested dose, five capsules t.i.d.
      Outcome measures were micronutrient concentrations in serum and red blood cells,
      vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire
      and 24 hour dietary recall interview), and mood and global functioning ratings.
      RESULTS: Seven children (70%) completed the study. Three (30%) terminated early
      for tolerability and compliance issues. Adverse effects were mild and transient,
      and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No
      differences occurred in BMI (p = 0.310) or waist-hip ratio (WHR; p = 0.674) pre-
      to postsupplementation. Four of the tested serum vitamin concentrations increased
      from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-alpha
      tocopherol; and folate (all p<0.05). The increase in serum 25-OH vitamin D
      approached significance (p = 0.063). No differences were found in dietary intake
      pre- to postsupplementation, suggesting that blood nutrient level increases were
      caused by EMP+. CONCLUSIONS: In this open prospective study, short-term use of
      EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect
      profile preferable to first-line psychotropic drugs for pediatric bipolar
      spectrum disorders. A double-blind, randomized clinical trial is feasible,
      appears safe, and is warranted by open-label clinical outcomes and plausible
      mechanisms of action, combined with documentation of increased serum
      concentrations of specific micronutrients.

PMID- 24138010
TI  - Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct
      disorder.
AB  - Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders
      (DBDs) (oppositional-defiant disorder or conduct disorder), with negative
      implications on treatment strategy and outcome. The aim of this study was to
      assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid
      with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and
      16 females, age range 12-18 years, mean age 14.9 +/- 2.0 years), diagnosed with a
      clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for
      School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to
      American Psychiatric Association, Diagnostic and Statistical Manual of Mental
      Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the
      patients were treated with quetiapine monotherapy (mean final dose 258 +/- 124
      mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%)
      were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2
      and CGI-Severity [CGI-S] <= 3 and improvement of at least 30% Children's Global
      Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS
      significantly improved (p<0.0001). Nine out of the 16 patients with suicidality
      (56.3%) had a reduction in this severe symptom during the follow-up.
      Nonresponders were more frequently males, and more frequently had an attention
      deficit/hyperactivity disorder (ADHD) comorbidity. Eight patients (20.0%)
      experienced moderate to severe sedation and eight (20.0%) experienced increased
      appetite and weight gain. In these severely impaired adolescents, quetiapine
      monotherapy was well tolerated and effective in>50% of the patients.

PMID- 24138011
TI  - Aripiprazole treatment of irritability associated with autistic disorder and the
      relationship between prior antipsychotic exposure, adverse events, and weight
      change.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of prior
      antipsychotic exposure (PAE) on safety and tolerability outcomes in pediatric
      subjects receiving aripiprazole treatment. METHODS: This study was a post-hoc
      analysis of pooled data from two 8-week, double-blind, randomized, placebo
      controlled studies evaluating aripiprazole for the treatment of irritability in
      pediatric subjects with autistic disorder, aged 6-17 years. Subjects were
      stratified by PAE; adverse events (AEs), and changes in weight, and metabolic
      measures were evaluated. For subjects receiving aripiprazole, regardless of PAE,
      baseline weight, age, gender, and symptom severity were evaluated in a regression
      model predicting body weight change. RESULTS: Of 316 randomized subjects, 259
      (82.0%) were antipsychotic naive (AN) and 57 (18.0%) had a PAE. Aripiprazole
      treated AN subjects were more likely than PAE subjects to report somnolence
      (11.9% vs. 2.8%), sedation (22.7% vs. 11.1%), or fatigue (17.0% vs. 13.9%). Rates
      of extrapyramidal disorder and drooling, but not akathisia or tremor, were
      marginally higher in AN subjects. Overall, 10.8% of aripiprazole-treated AN
      subjects had at least one AE leading to discontinuation compared with 8.3% of
      aripiprazole-treated PAE subjects. AN subjects receiving aripiprazole had a
      larger change in weight from baseline to endpoint compared with those receiving
      placebo (1.9 vs. 0.7 kg; treatment difference 1.2 kg, 95% CI: 0.5, 1.9) than PAE
      subjects receiving aripiprazole compared with subjects receiving placebo (0.4 vs.
      -0.4 kg; treatment difference 0.9 kg, 95% CI: -0.6, 2.4). Regression analysis
      identified that younger subjects with higher baseline weight z-score were at
      highest risk for weight gain. There were no significant changes in metabolic
      measures compared with placebo in either group. CONCLUSIONS: Weight gain was more
      pronounced in AN subjects and more likely to occur in younger subjects with a
      higher baseline weight z-score. AN subjects were more likely to experience AEs
      related to somnolence. However, based on discontinuations rates from AEs, overall
      tolerability was good for both AN and PAE groups. CLINICAL TRIAL REGISTRATION:
      Study of aripiprazole in the treatment of children and adolescents with autistic
      disorder. Registry: www.clinicaltrials.gov . Identifiers: NCT00332241 and
      NCT00337571.

PMID- 24138012
TI  - Exacerbation of obsessive-compulsive disorder, generalized anxiety disorder, and
      chronic motor tics during treatment of attention-deficit/hyperactivity disorder:
      medication management in an older adolescent.

PMID- 24138013
TI  - Lamotrigine-induced facial tic in a pediatric bipolar disorder patient.

PMID- 24138014
TI  - Aspirin as an adjunctive treatment for childhood onset schizophrenia.

PMID- 24138015
TI  - Influence of texture on the perception of saltiness in wheat bread.
AB  - As a basis for sodium reduction in bread, the influence of crumb texture on the
      intensity of saltiness and the release of sodium ions during chewing was
      investigated. A coarse-pored bread crumb was created by extending the proofing
      time (90/120 min vs 20/40 min as control), whereas the omission of proofing
      resulted in a fine-pored crumb (0/0 min). A significantly faster sodium release
      from the coarse-pored bread compared to the fine-pored bread (constant sample
      weight) was measured in-mouth and in a mastication simulator. This explained the
      significantly enhanced salty taste of the 90/120 min bread. Corresponding
      experiments with constant sample volumes revealed a significantly enhanced
      saltiness despite similar amounts of extracted sodium during the first seconds of
      chewing. Therefore, saltiness was influenced both by the velocity of sodium
      release and by crumb texture. Appropriate modification of crumb texture thus
      leads to enhanced saltiness, suggesting a new strategy for salt reduction in
      bread. 

PMID- 24138017
TI  - Enantioselective synthesis of axially chiral multifunctionalized biaryls via
      asymmetric Suzuki-Miyaura coupling.
AB  - Substituted 2-formylarylboronic acids were successfully employed as substrates
      for asymmetric Suzuki-Miyaura coupling. By virtue of the coupling with
      dialkoxyphosphinyl substituted naphthyl bromides and 2-nitronaphthalen-1-yl
      triflouromethanesulfonate, a series of novel multifunctionalized axially chiral
      biaryls were prepared in 53-97% yields with up to 97% ee using palladium-Cy-MOP
      as the catalyst. The methodology provides a highly efficient and practical
      strategy for the synthesis of novel multifunctionalized axially chiral biaryls. 

PMID- 24138016
TI  - Generation of highly purified neural stem cells from human adipose-derived
      mesenchymal stem cells by Sox1 activation.
AB  - Neural stem cells (NSCs) are ideal candidates in stem cell-based therapy for
      neurodegenerative diseases. However, it is unfeasible to get enough quantity of
      NSCs for clinical application. Generation of NSCs from human adipose-derived
      mesenchymal stem cells (hAD-MSCs) will provide a solution to this problem.
      Currently, the differentiation of hAD-MSCs into highly purified NSCs with
      biological functions is rarely reported. In our study, we established a three
      step NSC-inducing protocol, in which hAD-MSCs were induced to generate NSCs with
      high purity after sequentially cultured in the pre-inducing medium (Step1), the
      N2B27 medium (Step2), and the N2B27 medium supplement with basic fibroblast
      growth factor and epidermal growth factor (Step3). These hAD-MSC-derived NSCs
      (adNSCs) can form neurospheres and highly express Sox1, Pax6, Nestin, and
      Vimentin; the proportion was 96.1% +/- 1.3%, 96.8% +/- 1.7%, 96.2% +/- 1.3%, and
      97.2% +/- 2.5%, respectively, as detected by flow cytometry. These adNSCs can
      further differentiate into astrocytes, oligodendrocytes, and functional neurons,
      which were able to generate tetrodotoxin-sensitive sodium current. Additionally,
      we found that the neural differentiation of hAD-MSCs were significantly
      suppressed by Sox1 interference, and what's more, Step1 was a key step for the
      following induction, probably because it was associated with the initiation and
      nuclear translocation of Sox1, an important transcriptional factor for neural
      development. Finally, we observed that bone morphogenetic protein signal was
      inhibited, and Wnt/beta-catenin signal was activated during inducing process, and
      both signals were related with Sox1 expression. In conclusion, we successfully
      established a three-step inducing protocol to derive NSCs from hAD-MSCs with high
      purity by Sox1 activation. These findings might enable to acquire enough
      autologous transplantable NSCs for the therapy of neurodegenerative diseases in
      clinic.

PMID- 24138018
TI  - Studies of iron(III) porphyrinates containing silanethiolate ligands.
AB  - The chemistry of several iron(III) porphyrinates containing silanethiolate
      ligands is described. The complexes are prepared by protonolysis reactions of
      silanethiols with the iron(III) precursors, [Fe(OMe)(TPP)] and [Fe(OH)(H2O)(TMP)]
      (TPP = dianion of meso-tetraphenylporphine; TMP = dianion of meso
      tetramesitylporphine). Each of the compounds has been fully characterized in
      solution and the solid state. The stability of the silanethiolate complexes
      versus other iron(III) porphyrinate complexes containing sulfur-based ligands
      allows for an examination of their reactivity with several biologically relevant
      small molecules including H2S, NO, and 1-methylimidazole. Electrochemically, the
      silanethiolate complexes display a quasi-reversible one-electron oxidation event
      at potentials higher than that observed for an analogous arenethiolate complex.
      The behavior of these complexes versus other sulfur-ligated iron(III)
      porphyrinates is discussed. 

PMID- 24138019
TI  - Seroconversion and semen shedding in rams experimentally infected with Brucella
      ovis.
AB  - AIM: To determine the time taken for rams to develop antibodies to Brucella ovis
      in serum, shed B. ovis in semen and develop lesions of epididymitis following
      infection with B. ovis. METHODS: Fifteen 19-month-old rams were artificially
      infected with B. ovis by inoculation of infected semen onto the nasal and rectal
      mucus membranes (Day 0). Serum was collected from each ram at 2 to 8-day
      intervals and tested at commercial laboratories using a complement fixation test
      (CFT) and an ELISA. Cut-off values for the CFT were 0-4/4 negative; 1/8-3/8
      suspicious and 4/8-4/128 positive, and for the ELISA were <10% negative; >=10 to
      <50% suspicious and >=50% positive. Selected serum samples were also tested using
      a gel diffusion test (GDT). At 7 to 8-day intervals semen was collected for
      bacterial culture and the scrotal contents were palpated to identify lesions of
      epididymitis. The study was terminated after 56 days. RESULTS: On Day 28 B. ovis
      was isolated from the semen of one ram and by Day 49 it was isolated from the
      semen of 10 rams. All 10 rams had suspicious or positive ELISA or CFT titres by
      Day 36 and 56, respectively. The GDT results were all negative on Day 36 and in
      general did not become positive in individual rams until 7-28 days after semen
      shedding commenced. Epididymitis was detected in one ram on Day 36; by Day 56
      eight rams had epididymitis detectable by scrotal palpation. CONCLUSIONS: The B.
      ovis ELISA test identified infected rams at an earlier stage than the CFT; this
      was at 19-36 days after exposure. Rams can begin shedding B. ovis in semen as
      early as 28 days after exposure and lesions of epididymitis develop as early as
      36 days after exposure. CLINICAL RELEVANCE: During a test and slaughter campaign
      for the control of B. ovis, the most appropriate serological re-testing interval
      is likely to be around 28 days (4 weeks) using the ELISA with or without the CFT,
      although caution is required in interpretation of "suspicious" ELISA results.
      Following a B. ovis breakdown, two negative CFT or ELISA tests 60 days apart are
      recommended to confirm freedom from infection, supporting current guidelines.

PMID- 24138020
TI  - Cost-effectiveness of Acupuncture for Chronic Nonspecific Low Back Pain.
AB  - Cost-effectiveness is a major criterion underpinning decisions in mainstream
      health care. Acupuncture is increasingly used in patients with chronic lower back
      pain (LBP), but there is a lack of evidence on cost-effectiveness. The objective
      of this study was to assess the cost-effectiveness of acupuncture in alleviating
      chronic LBP either alone or in conjunction with standard care compared with
      patients receiving routine care, and/or sham. To determine effectiveness, we
      undertook meta-analyses which found a significant improvement in pain in those
      receiving acupuncture and standard care compared with those receiving standard
      care alone. For acupuncture and standard care vs. standard care and sham, a weak
      positive effect was found for weeks 12 to 16, but this was not significant. For
      acupuncture alone vs. standard care alone, a significant positive effect was
      found at week 8, but not at weeks 26 or 52. The main outcome parameters for our
      cost-effectiveness analysis were the incremental cost-effectiveness ratio (ICER)
      of acupuncture treatment presented as cost (A$) per disability-adjusted life-year
      (DALY) saved. The WHO benchmark for a very highly cost-effective intervention is
      one that costs less than gross domestic product per capita per quality-adjusted
      life-year (QALY) gained or DALY averted, or less than around $A52,000 in 2009
      (the base year for the analysis). According to this threshold, acupuncture as a
      complement to standard care for relief of chronic LBP is highly cost-effective,
      costing around $48,562 per DALY avoided. When comorbid depression is alleviated
      at the same rate as pain, cost is around $18,960 per DALY avoided. Acupuncture as
      a substitute for standard care was not found to be cost-effective unless comorbid
      depression was included. According to the WHO cost-effectiveness threshold
      values, acupuncture is a cost-effective treatment strategy in patients with
      chronic LBP. 

PMID- 24138021
TI  - Variation in the implementation of California's Full Service Partnerships for
      persons with serious mental illness.
AB  - OBJECTIVE: This study examined variation in the implementation of California's
      Full Service Partnerships (FSPs), which are supported housing programs that do
      "whatever it takes" to improve outcomes among persons with serious mental illness
      who are homeless or at risk of homelessness. DATA SOURCES/SETTING: Ninety-three
      FSPs in California. STUDY DESIGN: A mixed methods approach was selected to
      develop a better understanding of the complexity of the FSP programs. The design
      structure was a combined explanatory and exploratory sequential design (qual
      >QUAN->qual) where a qualitative focus group was used to develop a quantitative
      survey that was followed by qualitative site visits. The survey was used to
      describe the breadth of variation based on fidelity to the Housing First model,
      while the site visits were used to provide a depth of information on high- versus
      low-fidelity programs. PRINCIPAL FINDINGS: We found substantial variation in
      implementation among FSPs. Fidelity was particularly low along domains related
      with housing and service philosophy, indicating that many FSPs implemented a rich
      array of services but applied housing readiness requirements and did not adhere
      to consumer choice in housing. CONCLUSIONS: There remains room for improvement in
      the recovery-orientation of FSPs. Fortunately, we have identified several
      processes by which program managers and counties can increase the fidelity of
      their programs.

PMID- 24138022
TI  - Childhood hepatocellular carcinoma: a clinicopathological study of 12 cases with
      special reference to EpCAM.
AB  - AIMS: To elucidate the characteristics of hepatocellular carcinoma (HCC) in
      children. METHODS AND RESULTS: A retrospective search of our database identified
      12 children with HCC (aged 10 months to 11 years; male/female ratio of 5:7).
      Their pathological features were compared with those of adult HCCs (n = 20),
      fibrolamellar HCCs (n = 14), and hepatoblastomas (n = 15). All childhood HCCs
      developed on a background of cirrhosis resulting from tyrosinaemia type 1 (n =
      4), bile salt export transporter deficiency (n = 4), biliary atresia (n = 3), and
      long-standing total parenteral nutrition (n = 1). HCCs in cases of tyrosinaemia
      type 1 always had clear cell changes, solid architecture, and only mild nuclear
      atypia, whereas the morphological features of HCCs in the other conditions were
      basically similar to those of adult HCCs. On immunostaining, all cases of
      childhood HCC were positive for epithelial cell adhesion molecule (EpCAM);
      expression was diffuse (>50% of cancer cells) in 11 cases, and particularly
      strong in six children, all aged <3 years. In contrast, EpCAM was only focally
      expressed in three cases of adult HCC (15%). EpCAM was also expressed in most
      fibrolamellar HCCs and hepatoblastomas, but these two neoplasms differed from
      childhood HCCs in the expression of CK7, beta-catenin, and p53. CONCLUSIONS: The
      diffuse expression of EpCAM characterizes childhood HCC, and may indicate
      immaturity of neoplastic cells.

PMID- 24138024
TI  - Correlations between blood-brain barrier disruption and neuroinflammation in an
      experimental model of penetrating ballistic-like brain injury.
AB  - Abstract Blood-brain barrier (BBB) disruption is a pathological hallmark of
      severe traumatic brain injury (TBI) and is associated with neuroinflammatory
      events contributing to brain edema and cell death. The goal of this study was to
      elucidate the profile of BBB disruption after penetrating ballistic-like brain
      injury (PBBI) in conjunction with changes in neuroinflammatory markers. Brain
      uptake of biotin-dextran amine (BDA; 3 kDa) and horseradish peroxidase (HRP; 44
      kDa) was evaluated in rats at 4 h, 24 h, 48 h, 72 h, and 7 days post-PBBI and
      compared with the histopathologic and molecular profiles for inflammatory
      markers. BDA and HRP both displayed a uniphasic profile of extravasation,
      greatest at 24 h post-injury and which remained evident out to 48 h for HRP and 7
      days for BDA. This profile was most closely associated with markers for adhesion
      (mRNA for intercellular adhesion molecule-1) and infiltration of peripheral
      granulocytes (mRNA for matrix metalloproteinase-9 [MMP-9] and myeloperoxidase
      staining). Improvement of BBB dysfunction coincided with increased expression of
      markers implicated in tissue remodeling and repair. The results of this study
      reveal a uniphasic and gradient opening of the BBB after PBBI and suggest MMP-9
      and resident inflammatory cell activation as candidates for future
      neurotherapeutic intervention after PBBI.

PMID- 24138025
TI  - Mechanical stress in Arabidopsis leaves orients microtubules in a 'continuous'
      supracellular pattern.
AB  - BACKGROUND: Cortical microtubules form a dynamic network and continuously undergo
      shrinking (catastrophe), pausing and rebuilding (rescue). The advantage of such a
      dynamic system is that it may mediate appropriate responses in a short time span.
      Microtubules are known to play a pivotal role in determining the orientation of
      the cellulose microfibril deposition in the plant cell wall. The latter is a
      solid exoskeleton surrounding the protoplast. It forms the physical framework
      that interconnects most cells and has to bear the tensile stresses within the
      tissue. Here we describe the effect of externally applied pressure on microtubule
      organization in growing Arabidopsis leaves. RESULTS: Confocal microscopy
      examination of transgenic plants bearing GFP-tagged TUA6 proteins led to the
      observation that application of an additional mechanical pressure on growing
      Arabidopsis leaves triggers an excessive bundling of microtubules within the
      individual cell. Besides, the microtubules seem to align in neighboring cells,
      creating a 'continuous' supracellular pattern. This effect occurs within 3 hours
      after applied external force and is age-dependent, whereby only cells of leaves
      up to 19 days after sowing (DAS) are susceptible to the applied pressure.
      CONCLUSIONS: Upon externally applied pressure on developing Arabidopsis leaves,
      microtubules bundle and rearrange to form seemingly continuous supracellular
      patterns. As microtubules guide the cellulose synthase complexes, this observed
      reorganisation pattern probably affects the cellulose deposition, contributing to
      the reinforcement of the cell wall in a particular position to cope with the
      extra-applied pressure. The age-effect is reasonable, since younger cells, which
      are actively shaping their cell walls, are more vulnerable to altered mechanical
      stresses while in leaves older than 19 DAS, the walls are more robust and
      therefore can sustain the applied forces.

PMID- 24138023
TI  - SERCA2a gene therapy in heart failure: an anti-arrhythmic positive inotrope.
AB  - Therapeutic options that directly enhance cardiomyocyte contractility in chronic
      heart failure (HF) therapy are currently limited and do not improve prognosis. In
      fact, most positive inotropic agents, such as beta-adrenoreceptor agonists and
      PDE inhibitors, which have been assessed in HF patients, cause increased
      mortality as a result of arrhythmia and sudden cardiac death. Cardiac
      sarcoplasmic reticulum Ca(2)(+) -ATPase2a (SERCA2a) is a key protein involved in
      sequestration of Ca(2)(+) into the sarcoplasmic reticulum (SR) during diastole.
      There is a reduction of SERCA2a protein level and function in HF, which has been
      successfully targeted via viral transfection of the SERCA2a gene into cardiac
      tissue in vivo. This has enhanced cardiac contractility and reduced mortality in
      several preclinical models of HF. Theoretical concerns have been raised regarding
      the possibility of arrhythmogenic adverse effects of SERCA2a gene therapy due to
      enhanced SR Ca(2)(+) load and induction of SR Ca(2)(+) leak as a result. Contrary
      to these concerns, SERCA2a gene therapy in a wide variety of preclinical models,
      including acute ischaemia/reperfusion, chronic pressure overload and chronic
      myocardial infarction, has resulted in a reduction in ventricular arrhythmias.
      The potential mechanisms for this unexpected beneficial effect, as well as
      mechanisms of enhancement of cardiac contractile function, are reviewed in this
      article.

PMID- 24138027
TI  - Migration and dispersal may drive to high genetic variation and significant
      genetic mixing: the case of two agriculturally important, continental hoverflies
      (Episyrphus balteatus and Sphaerophoria scripta).
AB  - Population structure of pests and beneficial species is an important issue when
      designing management strategies to optimize ecosystem services. In this study, we
      investigated for the first time the population structure at a continental scale
      of two migratory species of hoverflies providing both pest regulation and
      pollination services [Episyrphus balteatus and Sphaerophoria scripta (Diptera:
      Syrphidae)]. To achieve this objective, we used two sets of 12 species-specific
      microsatellite markers on a large-scale sampling from all over Europe. Our
      findings showed a high level of genetic mixing resulting in a lack of genetic
      differentiation at a continental scale and a great genetic diversity in the two
      species. All the pairwise FST values between European localities were less 0.05
      in the two species. These low values reflect a large-scale genetic mixing
      probably caused by the existence of frequent migratory movements in the two
      species. Mantel tests revealed isolation-by-distance pattern on the East-West
      axis, but not on the North-South axis. This isolation-by-distance pattern
      confirms the existence of North-South migratory movements in both directions and
      suggests an important step by step dispersal. Population features shown by this
      study are common in invasive species and pests, but are not often observed in
      beneficial species. They reflect great colonization abilities and a high adaptive
      potential when dealing with a changing environment. Our results highlight the two
      studied species as particularly interesting beneficial insects for pollination
      and pest predation in the current context of global change. 

PMID- 24138026
TI  - Disruption of clathrin-mediated trafficking causes centrosome overduplication and
      senescence.
AB  - The Hsc70 cochaperone, G cyclin-associated kinase (GAK), has been shown to be
      essential for the chaperoning of clathrin by Hsc70 in the cell. In this study, we
      used conditional GAK knockout mouse embryonic fibroblasts (MEFs) to determine the
      effect of completely inhibiting clathrin-dependent trafficking on the cell cycle.
      After GAK was knocked out, the cells developed the unusual phenotype of having
      multiple centrosomes, but at the same time failed to divide and ultimately became
      senescent. To explain this phenotype, we examined the signaling profile and found
      that mitogenic stimulation of the GAK KO cells and the control cells were similar
      except for increased phosphorylation of Akt. In addition, the disruption of
      intracellular trafficking caused by knocking out GAK destabilized the lysosomal
      membranes, resulting in DNA damage due to iron leakage. Knocking down clathrin
      heavy chain or inhibiting dynamin largely reproduced the GAK KO phenotype, but
      inhibiting only clathrin-mediated endocytosis by knocking down adaptor protein
      (AP2) caused growth arrest and centrosome overduplication, but no DNA damage or
      senescence. We conclude that disruption of clathrin-dependent trafficking induces
      senescence accompanied by centrosome overduplication because of a combination of
      DNA damage and changes in mitogenic signaling that uncouples centrosomal
      duplication from DNA replication. 

PMID- 24138028
TI  - Contributions of simultaneous multiplane echocardiographic imaging in daily
      clinical practice.

PMID- 24138030
TI  - Over-expression of an inactive mutant cathepsin D increases endogenous alpha
      synuclein and cathepsin B activity in SH-SY5Y cells.
AB  - Parkinson's disease is a neurodegenerative movement disorder. The histopathology
      of Parkinson's disease comprises proteinaceous inclusions known as Lewy bodies,
      which contains aggregated alpha-synuclein. Cathepsin D (CD) is a lysosomal
      protease previously demonstrated to cleave alpha-synuclein and decrease its
      toxicity in both cell lines and mouse brains in vivo. Here, we show that
      pharmacological inhibition of CD, or introduction of catalytically inactive
      mutant CD, resulted in decreased CD activity and increased cathepsin B activity,
      suggesting a possible compensatory response to inhibition of CD activity.
      However, this increased cathepsin B activity was not sufficient to maintain alpha
      synuclein degradation, as evidenced by the accumulation of endogenous alpha
      synuclein. Interestingly, the levels of LC3, LAMP1, and LAMP2, proteins involved
      in autophagy-lysosomal activities, as well as total lysosomal mass as assessed by
      LysoTracker flow cytometry, were unchanged. Neither autophagic flux nor
      proteasomal activities differs between cells over-expressing wild-type versus
      mutant CD. These observations point to a critical regulatory role for that
      endogenous CD activity in dopaminergic cells in alpha-synuclein homeostasis which
      cannot be compensated for by increased Cathepsin B. These data support the
      potential need to enhance CD function in order to attenuate alpha-synuclein
      accumulation as a therapeutic strategy against development of synucleinopathy.

PMID- 24138031
TI  - Inhibition of hepatobiliary transporters by a novel kinase inhibitor contributes
      to hepatotoxicity in beagle dogs.
AB  - PF-022 (1) is a novel polycyclic benzothiophene kinase inhibitor selective for
      mitogen-activated protein kinase-activated protein kinase 2 (MK2). Compound 1
      emerged as an inhibitor bearing submicromolar potency against MK2 (IC50 5 nM) and
      demonstrated projected human pharmacokinetics sufficient for oral dosing.
      However, following a single, oral administration of 1 to beagle dogs, animals
      experienced an acute liver injury characterized by increases in biomarkers
      associated with hepatotoxicity; particularly noteworthy was the reversible
      elevation in bile salts and total bilirubin. Accompanying this observation was an
      ADME appraisal which included hepatic bioactivation of 1 in multiple species and
      the in vitro inhibition of P-glycoprotein (P-gp; IC50 21 MUM). Simply attenuating
      the bioactivation via structural modification proved ineffective in improving the
      in vivo tolerability of this polycyclic scaffold. Hence, disruption of
      hepatobiliary transporters by the compound series was hypothesized as the likely
      mechanism contributing to the acute hepatotoxicity. Indeed, closer in vitro
      examination employing transporter gene overexpressing MDCK cell lines and
      membrane vesicles revealed potent compound-dependent inhibition of human multi
      drug resistance-associated protein 2 (MRP2/ABCC2; IC50 38 MUM) and bile salt
      export pump (BSEP/ABCB11; IC50 10 MUM), two crucial hepatobiliary transport
      proteins accountable for bilirubin and bile salt homeostasis, respectively.
      Subsequent introduction of pKa-altering modifications to a second generation
      compound PF029 proved successful in reducing its affinity for these key efflux
      transporters (MRP2 IC50 >>80 MUM; BSEP IC50 > 70 MUM; P-gp > 90 MUM),
      consequently mitigating this overt organ toxicity in dogs. 

PMID- 24138032
TI  - Evaluation of the effects of weaning diets on Escherichia coli O157 shedding,
      body weight, and fecal bacterial communities in beef calves.
AB  - Cattle are considered to be one of the primary reservoirs of Escherichia coli
      O157. In this study, the effects of weaning diets on E. coli O157 shedding, body
      weight, and fecal bacterial communities in beef calves were evaluated. A total of
      60 calves (28 heifers and 32 steers) were weaned and randomly assigned into two
      groups. A peanut/soy hull-based diet (Dry Feed, DF) and a corn silage-based diet
      (High Moisture, HM) were fed to the two groups, respectively, during the weaning
      and preconditioning period. Calf body weight was measured before weaning (BW) and
      14 days after weaning (AW14), and a fecal sample was collected from each calf at
      BW, AW14, as well as 56 days after weaning (AW56). The prevalence of O157 in
      feces was determined by CHROMagar(TM) O157 and polymerase chain reaction (PCR).
      Denaturing gradient gel electrophoresis (DGGE) was employed to analyze fecal
      bacterial communities. A significant decrease in body weight was observed during
      weaning, regardless of the calf diet (p<0.05). Calves fed the HM diet lost more
      weight than the DF-fed calves determined at 14 days after weaning (p<0.05). Both
      the CHROMagar(TM) and PCR results showed that the overall prevalence of O157
      increased significantly during weaning. Based on the CHROMagar(TM) method, O157
      increased from 16.6% at BW to 38.3% at AW14 (p<0.05) and stayed at the higher
      level during the preconditioning period (AW56). The increase in O157 prevalence
      was observed in HM-fed calves during weaning but not in DF-fed ones. Weaning also
      changed the profile of fecal bacterial communities (p<0.05). These results showed
      that weaning is a critical step in beef cattle production, not only because of
      its effects on body weight but also due to its impact on O157 shedding and
      gastrointestinal tract bacterial community establishment.

PMID- 24138033
TI  - Collaborative survey on the colonization of different types of cheese-processing
      facilities with Listeria monocytogenes.
AB  - Cross-contamination via equipment and the food-processing environment has been
      implicated as the main cause of Listeria monocytogenes transmission. The aim of
      this study, therefore, was to determine the occurrence and potential persistence
      of L. monocytogenes in 19 European cheese-processing facilities. A sampling
      approach in 2007-2008 included, respectively, 11 and two industrial cheese
      producers in Austria and the Czech Republic, as well as six Irish on-farm cheese
      producers. From some of the producers, isolates were available from sampling
      before 2007. All isolates from both periods were included in a strain collection
      consisting of 226 L. monocytogenes isolates, which were then typed by serotyping
      and pulsed-field gel electrophoresis (PFGE). In addition, metabolic fingerprints
      from a subset of isolates were obtained by means of Fourier-transform infrared
      (FTIR) spectroscopy. PFGE typing showed that six processing environments were
      colonized with seven persistent PFGE types of L. monocytogenes. Multilocus
      sequence typing undertaken on representatives of the seven persisting PFGE types
      grouped them into distinct clades on the basis of country and origin; however,
      two persistent strains from an Austrian and an Irish food processor were shown to
      be clonal. It was concluded that despite the fact that elaborate Hazard Analysis
      and Critical Control Point concepts and cleaning programs are applied, persistent
      occurrence of L. monocytogenes can take place during cheese making. L.
      monocytogenes sanitation programs could be strengthened by including rapid
      analytical tools, such as FTIR, which allow prescreening of potentially
      persistent L. monocytogenes contaminants.

PMID- 24138034
TI  - The role of genetics in the pathogenesis of periocular cutaneous neoplasms:
      implications for targeted therapy.
AB  - In the past, cutaneous malignancies of the periocular region were primarily
      treated surgically with few other options. As the genetic bases of these tumors
      have become elucidated, targeted therapies aimed specifically at pathways that
      are felt to be responsible for cellular proliferation and uncontrolled growth
      have emerged with new promise. This review contains a summary of the various
      genetic implications of cutaneous neoplasms as well as their corresponding
      targeted systemic therapies.

PMID- 24138035
TI  - The genetics of keratoconus.
AB  - Keratoconus is a bilateral, non-inflammatory corneal ectasia characterized by
      progressive conical thinning and protrusion of the cornea. Its etiology has long
      been believed to be multifactorial, with environmental, behavioral, and genetic
      factors all contributing to the disease process. This review focuses specifically
      on examining the evidence that supports a genetic basis for keratoconus.

PMID- 24138036
TI  - Fuchs endothelial cornea dystrophy: a review of the genetics behind disease
      development.
AB  - Fuchs dystrophy represents the most common form of endothelial dystrophy and is a
      significant cause of visual impairment. The cause of Fuchs dystrophy is a
      complicated combination of both genetic and environmental factors. Understanding
      the underlying causes of the disease can potentially lead to new medical
      treatments preventing loss of vision.

PMID- 24138038
TI  - The genetics of intraocular pressure.
AB  - Glaucoma is a leading cause of irreversible blindness. Intraocular pressure (IOP)
      is the only modifiable risk factor for glaucoma, yet there is little known about
      the molecular events that regulate IOP. Genetic and genomic studies have helped
      identify genes that influence IOP and could lead to the identification of
      biological pathways that serve as targets for novel pressure-modifying therapies.
      Genetic linkage studies resulted in the identification of several genes that
      cause Mendelian (autosomal dominant or autosomal recessive) forms of high
      pressure glaucoma, including MYOC. PITX2, FOXC1, and CYP1B1. Classical twin
      studies suggest that IOP is a heritable trait. More recently, genome-wide
      association studies (GWAS) have shown that common genetic variants in the GAS7
      and TMCO1 genomic regions are associated with elevated IOP. TMCO1 has also been
      associated with primary open-angle glaucoma in patients with advanced disease. A
      further study identifying additional genes contributing to IOP will be necessary
      to fully define the underlying genetic architecture of IOP.

PMID- 24138039
TI  - A review of the clinical and genetic aspects of aniridia.
AB  - Aniridia classically presents with a bilateral congenital absence or malformation
      of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop
      visually significant pre-senile cataracts and keratopathy. Additionally, they are
      at high risk for developing glaucoma. Classic aniridia can be genetically defined
      as the presence of a PAX6 gene deletion or loss-of-function mutation that results
      in haploinsufficiency. Variants of aniridia, which include a condition previously
      referred to as autosomal dominant keratitis, are likely due to PAX6 mutations
      that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK)
      is a progressive and potentially debilitating problem affecting aniridic
      patients. The current treatments for AAK are to replace the limbal stem cells
      through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for
      visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future
      therapies for AAK may be aimed at the genetic modification of corneal limbal stem
      cells.

PMID- 24138040
TI  - Genetics of ectopia lentis.
AB  - Hereditary ectopia lentis or lens subluxation can occur with and without systemic
      associations. Significant overlap can be found in the genetic mutations and
      pathogenesis of subluxated lenses in their isolated forms as well as with
      associated syndromes. Gene mutations have been identified for lens subluxation
      associated with Marfan syndrome, Weill Marchesani syndrome, Ectopia Lentis
      simplex, Ectopia Lentis et pupillae, Ehlers Danlos syndrome, homocystinuria, and
      sulfite oxidase deficiency. Herein we describe the ocular and systemic
      characteristics found in patients with ectopia lentis, as well as the gene
      mutations identified thus far.

PMID- 24138041
TI  - Deprivation amblyopia and congenital hereditary cataract.
AB  - Amblyopia is a neurodevelopmental disorder of vision associated with decreased
      visual acuity, poor or absent stereopsis, and suppression of information from one
      eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia),
      refractive error (anisometropic amblyopia), or deprivation from obstructed vision
      (deprivation amblyopia). 1 In the developed world, amblyopia is the most common
      cause of childhood visual impairment, 3 which reduces quality of life 4 and also
      almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment
      of amblyopia greatly depends on early detection and treatment of predisposing
      disorders such as congenital cataract, which is the most common cause of
      deprivational amblyopia. Understanding the genetic causes of congenital cataract
      leads to more effective screening tests, early detection and treatment of infants
      and children who are at high risk for hereditary congenital cataract.

PMID- 24138037
TI  - Gene therapy in corneal transplantation.
AB  - Corneal transplantation is the most commonly performed organ transplantation.
      Immune privilege of the cornea is widely recognized, partly because of the
      relatively favorable outcome of corneal grafts. The first-time recipient of
      corneal allografts in an avascular, low-risk setting can expect a 90% success
      rate without systemic immunosuppressive agents and histocompatibility matching.
      However, immunologic rejection remains the major cause of graft failure,
      particularly in patients with a high risk for rejection. Corticosteroids remain
      the first-line therapy for the prevention and treatment of immune rejection.
      However, current pharmacological measures are limited in their side-effect
      profiles, repeated application, lack of targeted response, and short duration of
      action. Experimental ocular gene therapy may thus present new horizons in
      immunomodulation. From efficient viral vectors to sustainable alternative
      splicing, we discuss the progress of gene therapy in promoting graft survival and
      postulate further avenues for gene-mediated prevention of allogeneic graft
      rejection.

PMID- 24138042
TI  - HLA associations in chronic vision threatening uveitis.
AB  - Chronic uveitides can lead to serious sequlae over time including blindness.
      Human Leukocyte antigen (HLA) plays an important role in immunological response
      of the eyes. Some of these uveitides are associated with certain Human Leukocyte
      antigen (HLA) types. This article reviews these relationships and their
      significance.

PMID- 24138043
TI  - Genetics of diabetic retinopathy.
AB  - Multiple studies have shown that genetic factors may play an important role in
      determining an individual's risk for the development of diabetic retinopathy (DR)
      and progression to proliferative DR. However, consistent and definitive genetic
      associations with DR across broad populations have been not been established.
      Numerous genes have been studied for their association with DR and the results of
      these investigations have most specifically pointed to three specific genes that
      are likely involved in DR development and progression. The gene coding for
      vascular endothelial growth factor, aldose reductase, and the receptor for
      advanced glycation end products have been extensively evaluated, and specific
      polymorphisms of these genes have been suggested to potentially increase the risk
      of DR development. In this paper, we have reviewed the published literature on
      the genetics of DR and the potential implications for DR development and
      progression.

PMID- 24138044
TI  - Vascular endothelial growth factor gene polymorphisms and vitreous proteome
      changes in diabetic retinopathy.
AB  - Ischemic retinal diseases, particularly diabetic retinopathy, continue to
      significantly impact vision and remain a leading cause of vision loss in working
      aged adults. Identifying specific genetic risk factors for ischemic-driven
      pathways that increase susceptibility to developing diabetic retinopathy is a
      priority to allow development of accurate risk assessment algorithms, employ
      earlier intervention, and design novel treatment strategies to reduce the
      associated visual complications. Single nucleotide polymorphisms (SNPs) in the
      VEGF gene have been shown to influence the expression of the VEGF protein.
      Several studies suggest that SNPs in the VEGF gene mediate genetic predisposition
      to diabetic retinopathy. In addition, alterations in the vitreous proteome,
      including carbonic anhydrase mediated vascular permeability, have been found to
      be associated with sight-threatening proliferative diabetic retinopathy and
      macular edema. Inhibition of these factors could provide new therapeutic
      opportunities for the treatment of diabetic retinopathy.

PMID- 24138045
TI  - Stargardt-Fundus flavimaculatus: recent advancements and treatment.
AB  - Stargardt disease is the most common form of autosomal recessive macular
      dystrophy. Mutation in the ABCA4 gene (ABCR protein) is responsible for disease
      manifestation in more than 95% of Stargardt patients. ABCA4 codes for a member of
      the ATP binding cassette transmembrane protein involved in the transport of all
      trans retinal. Dysfunction in this protein causes accumulation of lipofuscin,
      which is toxic to the RPE and photoreceptors. Presenting symptoms, fundus
      appearance, and progression of the disease are widely variable in this disease.
      Different imaging modalities have been utilized to study the presentation and
      evolution of fundus changes. Although there is ongoing research to better
      understand the disease process and ways to alternate its path, currently there is
      no treatment for Startgardt patients.

PMID- 24138046
TI  - Von hippel-lindau disease: a genetic and clinical review.
AB  - BACKGROUND: Von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited
      systemic cancer syndrome that gives rise to cystic and highly vascularized tumors
      in many organs, including the eye. Recent studies have contributed to the
      understanding of VHL pathophysiology, genetics, and the role of the VHL protein.
      This article reviews recent studies on VHL clinical findings, genetics and
      tumorigenesis. METHODS: Literature review of articles on VHL genetics with
      correlation to clinical findings. RESULTS: Genotype-phenotype correlation studies
      show that patients with a complete deletion mutation of the VHL gene, relative to
      participants with a missense or protein-truncating mutation, had better visual
      acuity and decreased tumorigenesis incidence of retinal hemangioblastomas. It has
      also been documented that higher levels of vascular endothelial growth factor
      (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular
      hemangioblastomas. The stromal foamy vacuolated cells seem to be the true tumor
      cells of the disease acting on the surrounding endothelial cells in ocular
      hemangioblastomas. Tumor cells and ocular lesions have shown increased levels of
      Erythropoietin (Epo), Epo receptor (EpoR), and CD133. Also, CXCR4, a CXC
      chemokine receptor, is expressed in retinal VHL hemangioblastomas. Recent studies
      suggest that the VHL mutation alone may not be sufficient to develop VHL
      associated neoplasms. Studies suggest that targeting various proteins along with
      anti-angiogenesis molecules may be a better therapeutic approach than targeting
      VEGF alone. CONCLUSION: Understanding of the mechanisms and genetics underlying
      VHL and its associated retinal hemangioblastomas has increased substantially in
      recent years. This knowledge suggests that future advances may include better
      identification of individuals at higher risk of vision loss and the development
      of novel individualized therapies.

PMID- 24138047
TI  - The hermansky-pudlak syndrome: clinical features and imperatives from an
      ophthalmic perspective.
AB  - The Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive condition
      comprising nine genetically heterogeneous entities that feature oculocutaneous
      albinism (OCA) and bleeding tendency as their principal clinical manifestations.
      The pathogenesis of HPS involves disturbances in the biogenesis and trafficking
      of lysosome-related organelles. While the ophthalmologist is trained to address
      the ocular manifestations of OCA, it is critical for the provider to consider HPS
      when examining OCA patients as its systemic sequelae may be associated with
      morbidity and mortality. If there is suspicion of HPS in a patient with albinism,
      the ophthalmologist should enlist the aid of consultants to confirm the diagnosis
      and monitor for systemic features. As the nine HPS subtypes explored in this
      article vary widely in the character and severity of their associated systemic
      manifestations, some authors advocate determining the specific gene defect in
      each HPS patient in order to optimize care and provide anticipatory guidance.

PMID- 24138048
TI  - X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype
      relationships.
AB  - X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes
      of juvenile progressive retinal-vitreal degeneration in males. To date, more than
      196 different mutations of the RS1 gene have been associated with XLRS. The
      mutation spectrum is large and the phenotype variable. This review will focus on
      the clinical features of XLRS and examine the relationship between phenotype and
      genotype.

PMID- 24138049
TI  - CRB1: one gene, many phenotypes.
AB  - Mutations in the CRB1 gene cause severe retinal degenerations, which may present
      as Leber congenital amaurosis, early onset retinal dystrophy, retinitis
      pigmentosa, or cone-rod dystrophy. Some clinical features should alert the
      ophthalmologist to the possibility of CRB1 disease. These features are nummular
      pigmentation of the retina, atrophic macula, retinal degeneration associated with
      Coats disease, and a unique form of retinitis pigmentosa named para-arteriolar
      preservation of the retinal pigment epithelium (PPRPE). Retinal degenerations
      associated with nanophthalmos and hyperopia, or with keratoconus, can serve as
      further clinical cues to mutations in CRB1. Despite this, no clear genotype
      phenotype relationship has been established in CRB1 disease. In CRB1-disease, as
      in other inherited retinal degenerations (IRDs), it is essential to diagnose the
      specific disease-causing gene for the disease as genetic therapy has progressed
      considerably in the last few years and might be applicable.

PMID- 24138050
TI  - Autosomal dominant hereditary optic neuropathy (ADOA): a review of the genetics
      and clinical manifestations of ADOA and ADOA+.
AB  - Autosomal dominant hereditary optic atrophy (ADOA), also known as Kjer's
      syndrome, is a common hereditary cause of progressive bilateral vision loss.
      Recent advancements in the understanding of the genetics of this condition have
      revealed that a single gene may account for a large portion of the clinical
      manifestations in these patients. It has long been recognized that in a not
      insignificant number of ADOA patients, a number of "plus" symptoms may follow
      decades after vision loss. It is important that clinicians recognize the
      potential link to "plus" manifestations. The goal of this manuscript is to
      provide for the general ophthalmologist a practical outline of the genetics and
      clinical manifestations of ADOA and the ADOA+.

PMID- 24138052
TI  - An update on the genetics of comitant strabismus.
AB  - Genetics play a significant role in the development of comitant strabismus and
      elucidating the relevant mechanisms that cause it may lead to the development of
      new therapeutic options. The genetics of strabismus are complex and involve the
      interactions of multiple genes. This article reviews the progress that has been
      made in the understanding of the genetic causes of comitant strabismus including
      linkage studies that have identified a variety of candidate sites, RNA and
      protein studies that have identified genes with altered regulation, and a study
      that establishes a role for genetic imprinting in comitant strabismus.

PMID- 24138051
TI  - The genetic basis of incomitant strabismus: consolidation of the current
      knowledge of the genetic foundations of disease.
AB  - In recent years, our understanding of the genetic foundations of incomitant
      strabismus has grown significantly. Much new understanding has been gleaned since
      the concept of congenital cranial dysinnervation disorders (CCDDs) was introduced
      in 2002, and the genetic basis of CCDDs continues to be elucidated. In this
      review, we aim to provide an update of the genetic and clinical presentation of
      these disorders. Disorders reviewed include Duane syndrome (DS), HOXA1 and HOXB1
      syndromes, Moebius syndrome, congenital fibrosis of the extraocular muscles
      (CFEOM), and horizontal gaze palsy with progressive scoliosis (HGPPS).

PMID- 24138053
TI  - Improvements in endoscopic urothelial tumor visualization.

PMID- 24138054
TI  - Incretin based therapies: bone protective effects.
AB  - Type 2 Diabetes Mellitus (T2D) and osteoporosis have been found recently to be
      tightly correlated. In fact, T2D can result in bone loss through different
      mechanisms resulting in alteration of bone matrix and inhibition of bone
      formation. Fracture risk also increases significantly. New antidiabetic agents,
      dipeptidyl peptidase-4 inhibitors and glucagon like peptide -1 agonists have
      shown promise in many fields beyond glycemic control. Benefits on the skeletal
      system are multiple through direct stimulation of osteoblasts, inhibition of
      advanced glycation end products and inhibition of bone resorption. However,
      clinical evidence in humans is still not enough to allow definitive conclusions. 

PMID- 24138056
TI  - Various bismuth oxyiodide hierarchical architectures: alcohothermal-controlled
      synthesis, photocatalytic activities, and adsorption capabilities for phosphate
      in water.
AB  - Controllable synthesis of morphology and composition of functional material
      through a similar method is very necessary to understand the related properties.
      In this study, we report a facile solvothermal route to synthesize a series of
      bismuth oxyiodide compounds, including BiOI, Bi7O9I3, and Bi4O5I2 hierarchical
      microspheres, under relatively mild conditions through only adjusting the types
      of alcohols. It was found that the viscosity of alcohol played key roles in
      determining the morphologies and compositions of the final products. UV-visible
      diffuse-reflectance spectra and theoretic calculations indicated that bismuth
      oxyiodides with different ratios of Bi:O:I clearly possessed different light
      absorption and energy band structures. As a result, the as-synthesized BiOI,
      Bi7O9I3, and Bi4O5I2 hierarchical microspheres displayed morphology- and
      composition-dependent photocatalytic activities for the degradation of rhodamine
      B (RhB) and colorless phenol under visible-light irradiation. On the basis of
      experimental results, the difference of photocatalytic activity of these bismuth
      oxyiodide compounds was discussed. Furthermore, hierarchical bismuth oxyiodide
      microspheres were also evaluated as adsorbents for removing phosphate from
      aqueous solution. The results showed that Bi7O9I3 and Bi4O5I2 hierarchical
      microspheres had good adsorption capabilities for phosphate in water because of
      their larger surface areas and hierarchical porous structures. 

PMID- 24138055
TI  - Identification of functional cis-regulatory elements by sequential enrichment
      from a randomized synthetic DNA library.
AB  - BACKGROUND: The identification of endogenous cis-regulatory DNA elements (CREs)
      responsive to endogenous and environmental cues is important for studying gene
      regulation and for biotechnological applications but is labor and time intensive.
      Alternatively, by taking a synthetic biology approach small specific DNA binding
      sites tailored to the needs of the scientist can be generated and rapidly
      identified. RESULTS: Here we report a novel approach to identify stimulus
      responsive synthetic CREs (SynCREs) from an unbiased random synthetic element
      (SynE) library. Functional SynCREs were isolated by screening the SynE libray for
      elements mediating transcriptional activity in plant protoplasts. Responsive
      elements were chromatin immunoprecipitated by targeting the active Ser-5
      phosphorylated RNA polymerase II CTD (Pol II ChIP). Using sequential enrichment,
      deep sequencing and a bioinformatics pipeline, candidate responsive SynCREs were
      identified within a pool of constitutively active DNA elements and further
      validated. These included bonafide biotic/abiotic stress-responsive motifs along
      with novel SynCREs. We tested several SynCREs in Arabidopsis and confirmed their
      response to biotic stimuli. CONCLUSIONS: Successful isolation of synthetic stress
      responsive elements from our screen illustrates the power of the described
      methodology. This approach can be applied to any transfectable eukaryotic system
      since it exploits a universal feature of the eukaryotic Pol II.

PMID- 24138057
TI  - Strong adhesion and cohesion of chitosan in aqueous solutions.
AB  - Chitosan, a load-bearing biomacromolecule found in the exoskeletons of
      crustaceans and insects, is a promising biopolymer for the replacement of
      synthetic plastic compounds. Here, surface interactions mediated by chitosan in
      aqueous solutions, including the effects of pH and contact time, were
      investigated using a surface forces apparatus (SFA). Chitosan films showed an
      adhesion to mica for all tested pH ranges (3.0-8.5), achieving a maximum value at
      pH 3.0 after a contact time of 1 h (Wad ~ 6.4 mJ/m(2)). We also found weak or no
      cohesion between two opposing chitosan layers on mica in aqueous buffer until the
      critical contact time for maximum adhesion (chitosan-mica) was reached. Strong
      cohesion (Wco ~ 8.5 mJ/m(2)) between the films was measured with increasing
      contact times up to 1 h at pH 3.0, which is equivalent to ~60% of the strongest,
      previously reported, mussel underwater adhesion. Such time-dependent adhesion
      properties are most likely related to molecular or molecular group reorientations
      and interdigitations. At high pH (8.5), the solubility of chitosan changes
      drastically, causing the chitosan-chitosan (cohesion) interaction to be repulsive
      at all separation distances and contact times. The strong contact time and pH
      dependent chitosan-chitosan cohesion and adhesion properties provide new insight
      into the development of chitosan-based load-bearing materials.

PMID- 24138058
TI  - Prospective observational study of acute postlumbar laminectomy MRI.
AB  - OBJECT: Patients who develop a lower-extremity neurological deficit after lumbar
      laminectomy present a diagnostic dilemma. In the setting of a neurological
      deficit, some surgeons use MRI to evaluate for symptomatic compression of the
      thecal sac. The authors conducted a prospective observational cohort study in
      patients undergoing open lumbar laminectomy for neurogenic claudication to
      document the MRI appearance of the postlaminectomy spine and to determine changes
      in thecal sac diameter caused by the accumulation of epidural fluid. METHODS:
      Eligible patients who were candidates for open lumbar laminectomy for neurogenic
      claudication at a single neurosurgical center between August 2007 and June 2009
      were enrolled. Preoperative and postoperative MRI of the lumbar spine was
      performed on the same MRI scanner. Postoperative MRI studies were completed
      within 36 hours of surgery. Routine clinical and surgical data were collected at
      the preoperative visit, during surgery, and postoperatively. Images were
      interpreted for the signal characteristics of the epidural fluid and for thecal
      diameter (region of interest [ROI]) by 2 blinded neuroradiologists. RESULTS:
      Twenty-four patients (mean age 69.7 years, range 30-83 years) were enrolled, and
      20 completed the study. Single-level laminectomy was performed in 6 patients, 2
      level in 12, and 3-level in 2. Preoperative canal measurements (ROI) at the most
      stenotic level averaged 0.26 cm(2) (range 0.0-0.46 cm(2)), and postoperative ROI
      at that same level averaged 0.95 cm(2) (range 0.46-2.05 cm(2)). The increase in
      ROI averaged 0.69 cm(2) (range 0.07-1.81 cm(2)). Seven patients (35%) had
      immediate postoperative weakness in at least 1 muscle group graded at 4+/5. The
      decline in examination was believed to be effort dependent and secondary to
      discomfort in the acute postoperative period. Those with weakness had smaller
      increases in ROI (0.51 cm(2)) than those with full strength (0.78 cm(2), p =
      0.1599), but none had evidence of worsened thecal compression. On the 1st
      postoperative day, 19 patients were at full strength and all patients were at
      full strength at their 15-day follow-up. The T1-weighted epidural fluid signal
      was isointense in 19 of the 20 patients. The T2-weighted epidural fluid signal
      was hyperintense in 9, isointense in 4, and hypointense in 7 patients.
      CONCLUSIONS: Immediately after lumbar laminectomy, the appearance of the thecal
      sac on MRI can vary widely. In most patients the thecal sac diameter increases
      after laminectomy despite the presence of epidural blood. In this observational
      cohort, a reduction in thecal diameter caused by epidural fluid did not correlate
      with motor function. Results in the small subset of patients where the canal
      diameter decreased due to epidural fluid compression of the thecal sac raises the
      question of the utility of immediate postoperative MRI.

PMID- 24138059
TI  - Bow hunter's syndrome: the use of dynamic magnetic resonance angiography and
      intraoperative fluorescent angiography.
AB  - Bow hunter's syndrome is a diagnosis typically made using dynamic digital
      subtraction angiography. The authors present the case of a 68-year-old woman who
      presented with symptoms consistent with bow hunter's syndrome that was accurately
      diagnosed utilizing noninvasive dynamic MR angiography. The dynamic MR angiogram
      clearly illustrated unilateral vertebral artery compression upon turning of the
      head. A subsequent CT of the cervical spine showed a ventral C-1 osteophyte
      within the foramen. The patient underwent posterior surgical decompression of the
      left vertebral artery. Sufficient decompression was confirmed using
      intraoperative fluorescent angiography with the patient's head turned. This case
      report is the first to illustrate that dynamic MR angiography can be a reliable
      and less invasive diagnostic tool. It can also be used to confirm sufficient
      postoperative decompression and monitor for recurrence. Intraoperative
      fluorescent angiography has been previously used in the evaluation of
      intracranial and extracranial vascular patency. This report is the first to show
      that fluorescent angiography can offer rapid and reliable intraoperative
      evaluation of vertebral artery decompression in bow hunter's syndrome. 

PMID- 24138060
TI  - Frontolateral pins for halo ring placement: reassessment of a common
      neurosurgical procedure with CT measurements of skull thickness.
AB  - OBJECT: Halo orthosis placement is a common neurosurgical procedure for the
      treatment of cervical spine injuries. Frontal sinus puncture by the anterior pins
      may occur using standard techniques, and up to 30% are dissatisfied with forehead
      scarring, especially women and African Americans. METHODS: The authors describe a
      frontolateral (FL) anterior pin site placement supported by high-resolution CT
      scan skull thickness measurements. The standard supraorbital (SO) pin site is
      several centimeters above the lateral orbit, whereas the FL pin site is 2-3 cm
      posterolateral to the SO site. Frontolateral placement is just anterior to the
      temporalis muscle close to a triangular anterior projection of the temporal
      hairline. For quantitative information on skull thickness at the SO and FT pin
      sites, thin 0.625-mm CT scan measurements of the outer table, diploic space, and
      inner table were obtained in 40 adults (80 sites). RESULTS: The mean values for
      total skull thickness at the SO and FT sites were not significantly different.
      The inner table was significantly thicker at the FL site in both males and
      females, buttressed by the nearby greater sphenoid wing. The mean total skull
      thickness was significantly less in females than in males, but the values were
      not significantly different at the SO and FL sites. CONCLUSIONS: The FL and SO
      anterior pin sites are comparable with respect to skull thickness CT
      measurements, with a significantly thicker inner table at the FL site. In the
      senior author's experience, the FL anterior pin site yielded secure fixation
      without skull perforation, neurovascular injury, or propensity to infection. The
      cosmetic result of the FL site is more acceptable, and the authors recommend its
      general usage be adopted.

PMID- 24138061
TI  - Alfred W. Adson (1887-1951): his contributions to surgery for tumors of the spine
      and spinal cord in the context of spinal tumor surgery in the late 19th and early
      20th centuries.
AB  - Alfred W. Adson was a pioneer in the field of neurosurgery. He described
      operations for a variety of neurosurgical diseases and developed surgical
      instruments. Under his leadership the Section of Neurological Surgery at the Mayo
      Clinic was established and he functioned as its first chair. Adson's
      contributions to the understanding of spinal and spinal cord tumors are less well
      known. This article reviews related medical records and publications and sets his
      contributions in the context of the work of other important pioneers in spinal
      tumor surgery at the time. 

PMID- 24138062
TI  - Predictive value of MRI in decision making for disc surgery for sciatica.
AB  - OBJECT: In a randomized controlled trial comparing surgery and prolonged
      conservative treatment for sciatica of 6-12 weeks' duration, more than one-third
      of patients assigned to conservative treatment underwent surgery. The objective
      of the present study was to evaluate whether MRI at baseline could have predicted
      this delayed surgery. METHODS: Independently evaluated qualitative and
      quantitative MRI findings were compared between those patients who did and those
      who did not undergo surgery during follow-up in the conservative care group. In
      addition, area under the receiver operating characteristic (ROC) curve analysis
      was used to assess how well MRI parameters discriminated between those who did
      and those who did not undergo delayed surgery (0.5-0.7 poor discrimination, >=
      0.7 acceptable discrimination). RESULTS: Of 142 patients assigned to receive
      prolonged conservative care, 55 patients (39%) received delayed surgery. Of the
      55 surgically treated patients, 71% had definite nerve root compression at
      baseline compared with 72% of conservatively treated patients (p = 0.76). Large
      disc herniations (size > 50% of spinal canal) were nearly equally distributed
      between those who did and those who did not undergo surgery (25% vs 21%, p =
      0.65). The size of the dural sac was smaller in the patients who underwent
      surgery (101.2 vs 122.9 mm(2), p = 0.01). However, the size of the dural sac
      discriminated poorly between those who did and those who did not undergo delayed
      surgery (area under ROC curve, 0.62). CONCLUSIONS: In patients who suffered from
      sciatica of 6-12 weeks' duration, MRI at baseline did not distinguish between
      patients who did and those who did not undergo delayed surgery.

PMID- 24138063
TI  - Minimally invasive removal of thoracic and lumbar spinal tumors using a
      nonexpandable tubular retractor.
AB  - OBJECT: Resection of spinal tumors traditionally requires bilateral subperiosteal
      muscle stripping, extensive laminectomy, and, in cases of foraminal extension,
      partial or radical facetectomy. Fusion is often warranted in cases of facetectomy
      to prevent deformity, pain, and neurological deterioration. Recent reports have
      demonstrated safety and efficacy of mini-open removal of these tumors using
      expandable tubular retractors. The authors report their experience with the
      minimally invasive removal of extradural foraminal and intradural-extramedullary
      tumors using the nonexpandable tubular retractor. METHODS: A retrospective chart
      review of consecutive patients who underwent minimally invasive resection of
      spinal tumors at Notre Dame Hospital was performed. RESULTS: Between December
      2005 and March 2012, 13 patients underwent minimally invasive removal of spinal
      tumors at Notre Dame Hospital, Montreal. There were 6 men and 7 women with a mean
      age of 55 years (range 20-80 years). There were 2 lumbar and 2 thoracic
      intradural-extramedullary tumors and 7 thoracic and 2 lumbar extradural foraminal
      tumors. Gross-total resection was achieved in 12 patients. Subtotal resection
      (90%) was attained in 1 patient because the tumor capsule was adherent to the
      diaphragm. The average duration of surgery was 189 minutes (range 75-540
      minutes), and the average blood loss was 219 ml (range 25-500 ml). There were no
      major procedure-related complications. Pathological analysis revealed benign
      schwannoma in 8 patients and meningioma, metastasis, plasmacytoma, osteoid
      osteoma, and hemangiopericytoma in 1 patient each. The average equivalent dose of
      postoperative narcotics after surgery was 66.3 mg of morphine. The average length
      of hospitalization was 66 hours (range 24-144 hours). All working patients
      returned to normal activities within 4 weeks. The average MRI and clinical follow
      up were 13 and 21 months, respectively (range 2-68 months). At last follow-up,
      92% of patients had improvement or resolution of pain with a visual analog scale
      score that improved from 7.8 to 1.2. All patients with neurological impairment
      improved. The American Spinal Injury Association grade improved in all but 1
      patient. CONCLUSIONS: Intradural-extramedullary and extradural tumors can be
      completely and safely resected through a minimally invasive approach using the
      nonexpandable tubular retractor. This approach may be associated with even less
      tissue destruction than mini-open techniques, translating into a quicker
      functional recovery. In cases of foraminal tumors, by eliminating the need for
      facetectomy, this minimally invasive approach may decrease the incidence of
      postoperative deformity and eliminate the need for adjunctive fusion surgery.

PMID- 24138065
TI  - Identification and biological activity of antifungal saponins from shallot (
      Allium cepa L. Aggregatum group).
AB  - The n-butanol extract of shallot basal plates and roots showed antifungal
      activity against plant pathogenic fungi. The purified compounds from the extract
      were examined for antifungal activity to determine the predominant antifungal
      compounds in the extract. Two major antifungal compounds purified were determined
      to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal
      activity against a wide range of fungi. The products of acid hydrolysis of ALA
      showed a reduced antifungal activity, suggesting that the compound's sugar chain
      is essential for its antifungal activity. Fungal cells treated with ALA showed
      rapid production of reactive oxygen species. The fungicidal action of ALA was
      partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide
      anion generation in the fungal cells may be related to the compound's action.
      Inoculation experiments showed that ALA protected strawberry plants against
      Colletotrichum gloeosporioides , indicating that ALA has the potential to control
      anthracnose of the plant. 

PMID- 24138064
TI  - Hospital costs and inpatient mortality among children undergoing surgery for
      congenital heart disease.
AB  - OBJECTIVE: To determine the association between hospital costs and risk-adjusted
      inpatient mortality among children undergoing surgery for congenital heart
      disease (CHD) in U.S. acute-care hospitals. DATA SOURCES/STUDY SETTINGS:
      Retrospective cohort study of 35,446 children in 2003, 2006, and 2009 Kids'
      Inpatient Database (KID). STUDY DESIGN: Cross-sectional logistic regression of
      risk-adjusted inpatient mortality and hospital costs, adjusting for a variety of
      patient-, hospital-, and community-level confounders. DATA COLLECTION/EXTRACTION
      METHODS: We identified relevant discharges in the KID using the AHRQ Pediatric
      Quality Indicator for pediatric heart surgery mortality, and linked these records
      to hospital characteristics from American Hospital Association Surveys and
      community characteristics from the Census. PRINCIPAL FINDINGS: Children
      undergoing CHD surgery in higher cost hospitals had lower risk-adjusted inpatient
      mortality (p=.002). An increase from the 25th percentile of treatment costs to
      the 75th percentile was associated with a 13.6 percent reduction in risk-adjusted
      mortality. CONCLUSIONS: Greater hospital costs are associated with lower risk
      adjusted inpatient mortality for children undergoing CHD surgery. The specific
      mechanisms by which greater costs improve mortality merit further exploration.

PMID- 24138067
TI  - Multimodality imaging of submitral left ventricular aneurysm.
AB  - Submitral left ventricular aneurysms are a rare nonischemic aneurysm thought to
      be developmental in origin. These aneurysms invariably occur at the site of
      posterior mitral annulus and lead to mitral valve incompetence. We hereby
      describe a case of a 30-year-old adult with a rare form of submitral left
      ventricular aneurysm involving whole of the posterior mitral annulus.
      Multimodality imaging with two-dimensional echocardiography, three-dimensional
      echocardiography, computed tomography and invasive left ventriculography helped
      the patient to undergo successful resection of the aneurysm along with mitral
      valve replacement. 

PMID- 24138066
TI  - Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous
      mutations in IER3IP1: insights into the natural history of a rare disorder.
AB  - Neonatal diabetes mellitus is known to have over 20 different monogenic causes. A
      syndrome of permanent neonatal diabetes along with primary microcephaly with
      simplified gyral pattern associated with severe infantile epileptic
      encephalopathy was recently described in two independent reports in which disease
      causing homozygous mutations were identified in the immediate early response-3
      interacting protein-1 (IER3IP1) gene. We report here an affected male born to a
      non-consanguineous couple who was noted to have insulin-requiring permanent
      neonatal diabetes, microcephaly, and generalized seizures. He was also found to
      have cortical blindness, severe developmental delay and numerous dysmorphic
      features. He experienced a slow improvement but not abrogation of seizure
      frequency and severity on numerous anti-epileptic agents. His clinical course was
      further complicated by recurrent respiratory tract infections and he died at 8
      years of age. Whole exome sequencing was performed on DNA from the proband and
      parents. He was found to be a compound heterozygote with two different mutations
      in IER3IP1: p.Val21Gly (V21G) and a novel frameshift mutation p.Phe27fsSer*25.
      IER3IP1 is a highly conserved protein with marked expression in the cerebral
      cortex and in beta cells. This is the first reported case of compound
      heterozygous mutations within IER3IP1 resulting in neonatal diabetes. The triad
      of microcephaly, generalized seizures, and permanent neonatal diabetes should
      prompt screening for mutations in IER3IP1. As mutations in genes such as NEUROD1
      and PTF1A could cause a similar phenotype, next-generation sequencing approaches
      such as exome sequencing reported here-may be an efficient means of uncovering a
      diagnosis in future cases. 

PMID- 24138068
TI  - Age-related alterations in gene expression of gingival fibroblasts stimulated
      with Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: Elderly people exhibit increased susceptibility to a
      number of autoimmune and infectious diseases, such as periodontitis. Although
      aging is reportedly associated with a decline in immune function, age-related
      alterations in periodontal tissue have remained elusive. In the present study, we
      comprehensively analyzed the effect of aging on the expression of selected genes
      using mouse gingival fibroblasts. MATERIAL AND METHODS: Gingival fibroblasts
      derived from young (8 wk of age) and old (>= 24 mo of age) C57BL/6 mice were
      stimulated with Porphyromonas gingivalis lipopolysaccharide or live P. gingivalis
      strain W83. Expression of cytokines/chemokines, innate immune receptors, growth
      factors, matrix metalloproteinases, tissue inhibitors of metalloproteinases and
      osteoclastogenesis-related molecules were evaluated using real-time polymerase
      chain reaction and ELISA for interleukin-6 and transforming growth factor-beta1.
      RESULTS: Gingival fibroblasts derived from old mice exhibited decreased gene
      expression of Il-6, Cxcl1, Tlr2, Tlr4, Irak3 (IRAK-M), Kgf, Timp1, Timp3 and
      Rankl under resting conditions, whereas the expression levels of Tgfbeta1, Mmp3,
      Mmp13 and Opg were increased. Age-related differences were also detected at the
      protein level. Although P. gingivalis W83 upregulated Vegf, Fgf-2 and Bmp2
      expression in both young and old gingival fibroblasts, the stimulatory effect on
      these genes was significantly lower in old gingival fibroblasts. CONCLUSION: Our
      findings demonstrated that aging altered the expression of a number of genes in
      gingival fibroblasts. Thus, alterations in the balance of these molecules could
      play a critical role in periodontitis progression in the elderly.

PMID- 24138070
TI  - Nutri-metabolomics: subtle serum metabolic differences in healthy subjects by NMR
      based metabolomics after a short-term nutritional intervention with two tomato
      sauces.
AB  - Postgenomics research and development is witnessing novel intersections of omics
      data intensive technology and applications in health and personalized nutrition.
      Chief among these is the nascent field of nutri-metabolomics that harnesses
      metabolomics platforms to discern person-to-person variations in nutritional
      responses. To this end, differences in the origin and ripening stage of fruits
      might have a strong impact on their phytochemical composition, and consequently,
      on their potential nutri-metabolomics effects on health. The objective of the
      present study was to evaluate the effects of a 4-week cross-over nutritional
      intervention on the metabolic status of 24 young healthy subjects. The
      intervention was carried out with two tomato sauces differing in their natural
      lycopene content, which was achieved by using tomatoes harvested at different
      times. Blood samples were drawn from each subject before and after each
      intervention period. Aqueous and lipid extracts from serum samples were analyzed
      by 1H-NMR metabolic profiling combined with analysis of variance simultaneous
      component analysis (ASCA) and multilevel simultaneous component analysis (MSCA).
      These methods allowed the interpretation of the variation induced by the main
      factors of the study design (sauce treatment and time). The levels of creatine,
      creatinine, leucine, choline, methionine, and acetate in aqueous extracts were
      increased after the intervention with the high-lycopene content sauce, while
      those of ascorbic acid, lactate, pyruvate, isoleucine, alanine were increased
      after the normal-lycopene content sauce. In conclusion, NMR-based metabolomics of
      aqueous and lipid extracts allowed the detection of different metabolic changes
      after the nutritional intervention. This outcome might partly be due to the
      different ripening state of the fruits used in production of the tomato sauces.
      The findings presented herein collectively attest to the emergence of the field
      of nutri-metabolomics as a novel subspecialty of postgenomics integrative
      biology.

PMID- 24138069
TI  - Integrative omics approach identifies interleukin-16 as a biomarker of emphysema.
AB  - Interleukin-16 (IL-16) is a multifunctional cytokine that has been associated
      with autoimmune and allergic diseases. To investigate comprehensively whether IL
      16 is also associated with chronic obstructive pulmonary disease (COPD) and
      emphysema, we performed an integrated analysis of multiple "omics" data. Over 500
      subjects participating in the COPDGene(r) study donated blood and were clinically
      characterized and genetically profiled. IL-16 mRNA levels were measured in
      peripheral blood mononuclear cells (PBMC), and protein levels were measured in
      fresh frozen plasma. A multivariate analysis found plasma IL-16 positively
      associated with age and body mass index, and negatively associated with current
      smoking and emphysema in the upper lobes. PBMC IL-16 expression was positively
      associated with gender and a composite score for airflow obstruction, emphysema,
      and gas trapping. Whole-genome expression quantitative trait locus (eQTL)
      analysis identified a novel IL-16 missense SNP (rs11556218) associated with lower
      IL-16 in plasma. In summary, an integrated "omics" analysis in a very large
      cohort identified an association between decreased IL-16 and emphysema and
      discovered a novel IL-16 cis-eQTL. Thus IL-16 plasma levels and IL-16 genotyping
      may be useful in a personalized medicine approach for lung disease.

PMID- 24138071
TI  - Investigation of molecular alterations of AKT-3 in triple-negative breast cancer.
AB  - AIMS: Triple-negative breast cancer (TNBC) is responsible for a disproportionate
      number of breast cancer (BC) deaths, owing to its intrinsic aggressiveness and a
      lack of treatment options, especially targeted therapies. Thus, there is an
      urgent need for the development of better targeted treatments for TNBC. Molecular
      alteration of AKT-3 was previously reported in oestrogen receptor (ER)-positive
      BC. AKT-3 has also been suggested to play a role in hormone-unresponsive BC. The
      aim of this study was to investigate molecular alterations of AKT-3 in TNBC, to
      perform associated survival analysis, and to compare these findings with the
      incidence of AKT-3 molecular alterations in ER-positive BC. RESULTS: Our study
      revealed AKT-3 amplification and deletions in 11% (9/82) and 13% (11/82) of
      TNBCs, respectively. In contrast, 1% (2/209) of ER-positive BCs were found to
      have AKT-3 amplifications and deletions. A higher prevalence of AKT-3 copy number
      gains was observed in TNBC [26% (21/82)] than in ER-positive BC [9% (19/209)].
      AKT-3 amplification together with Akt-3 protein expression was negatively
      associated with recurrence-free survival in TNBC. Furthermore, a negative
      association between high AKT-3 copy number and recurrence-free survival was
      observed. CONCLUSION: AKT-3 amplification could represent a potentially relevant
      oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to
      Akt-3 inhibitors.

PMID- 24138073
TI  - Low frequency resonant impulsive Raman modes reveal inversion mechanism for
      azobenzene.
AB  - Azobenzenes are versatile photoswitches that find application in optical memory,
      light-driven motors, and molecular gating. Despite many studies, the molecular
      details of their light induced trans to cis isomerization are still debated. To
      inform this discussion we probed the low frequency skeletal motions in an
      azobenzene derivative, 4-nitro-4'-dimethylamino-azobenzene (NDAB), with resonant
      impulsive stimulated Raman spectroscopy (RISRS). Four previously unobserved modes
      at 14, 47, 150, and 201 cm(-1) were found. Of these, the ~50 cm(-1) inversion
      motion and the ~15 cm(-1) torsional motion had particularly large intensities,
      suggesting that the excited state potential energy surface is steeply sloped
      along these coordinates in the Franck-Condon region. These data support a model
      in which NDAB isomerizes predominantly along a prompt inversion coordinate as
      well as a slower torsional motion that mitigates the phenyl-phenyl interactions
      on the pathway to the isomerized product. 

PMID- 24138072
TI  - Clinical and laboratory predictive markers for acute dengue infection.
AB  - BACKGROUND: Early diagnosis of dengue virus infection during the febrile stage is
      essential for adjusting appropriate management. This study is to identify the
      predictive markers of clinical and laboratory findings in the acute stage of
      dengue infection during a major outbreak of dengue virus type 1 that occurred in
      southern Taiwan during 2007. A retrospective, hospital-based study was conducted
      at a university hospital in southern Taiwan from January to December, 2007.
      Patient who was reported for clinically suspected dengue infection was enrolled.
      Laboratory-positive dengue cases are confirmed by enzyme-linked immunosorbent
      assay of specific dengue IgM, fourfold increase of dengue-specific IgG titers in
      convalescent serum, or by reverse transcription-polymerase chain reaction (RT
      PCR) of dengue virus. RESULTS: The suspected dengue cases consist of 100 children
      (<= 18 years) and 481 adults. Among the 581 patients, 67 (67%) children and 309
      (64.2%) adults were laboratory-confirmed. Patients who had laboratory
      indeterminate were excluded. Most cases were uncomplicated and 3.8% of children
      and 2.9% of adults developed dengue hemorrhagic fever or dengue shock syndrome
      (DHF/DSS). The overall mortality rate in those with DHF/DSS was 7.1%, and the
      average duration of hospitalization was 20 days. The most common symptoms/signs
      at admission were myalgia (46.8%), petechiae (36.9%) and nausea/vomiting (33.5%).
      The most notable laboratory findings included leukopenia (2966 +/- 1896/cmm),
      thrombocytopenia (102 +/- 45 * 103/cmm), prolonged activated partial
      thromboplastin time (aPTT) (45 +/- 10 s), and elevated serum levels of
      aminotransferase (AST, 166 +/- 208 U/L; ALT, 82 +/- 103 U/L) and low C - reactive
      protein (CRP) (6 +/- 11 mg/L). Based on the clinical features for predicting
      laboratory-confirmed dengue infection, the sensitivities of typical rash,
      myalgia, and positive tourniquet test are 59.2%, 46.8%, and 34.2%, while the
      specificities for above features are 75.4%, 53.5% and 100%, respectively. The
      positive predictive value (PPV) for combination of leukopenia, thrombocytopenia
      (< 150 * 103/cmm), elevated aminotransferase (AST/ALT > 1.5) and low CRP (< 20
      mg/L) is 89.5%, while the negative predictive value is 37.4%. Furthermore, the
      PPV of the combination was increased to 93.1% by adding prolonged aPTT (>38
      secs). CONCLUSIONS: Leukopenia, thrombocytopenia, elevated aminotransferases, low
      CRP and prolonged aPTT, were useful predictive markers for early diagnosis of
      dengue infection during a large outbreak in southern Taiwan.

PMID- 24138074
TI  - Risk factors for cardiovascular disease in psoriasis: relation to inflammation
      assessed by the severity and duration of illness.
AB  - BACKGROUND: Recent studies have shown that psoriasis is associated with risk
      factors for cardiovascular diseases (CVDs). OBJECTIVES: To evaluate the
      epidemiological profile of patients with psoriasis, focusing on the risk factors
      for CVDs and inflammation. MATERIALS & METHODS: Patients with a diagnosis of
      psoriasis who were attended at the dermatology outpatient clinic of a university
      hospital were evaluated. RESULTS: 229 adult patients of mean age 50 years, among
      whom 52% were male, were evaluated. Twenty patients (8.7%) were concomitantly
      affected by psoriatic arthritis. From analysis on laboratory tests from 177
      patients, we saw that 111 (62.7%) were dyslipidemic and that among these, only 9
      (8%) were undergoing treatment. 35.6% presented abnormal glycemia tests, but 22%
      were not having any treatment for the glycemic alteration observed. We analyzed
      possible associations of the severity of psoriasis and length of time with the
      disease with lipid disorders, glycemic disorders and systemic arterial
      hypertension, but did not find any significant associations. CONCLUSION: The
      findings observed in this study corroborate previous findings in similar studies,
      thus demonstrating that the prevalence of risk factors for CVDs among patients
      with psoriasis is greater than in the general population, but that a large
      proportion of such patients do not undergo treatment for this. We did not find
      any possible association between the inflammatory process and the genesis of risk
      factors for CVDs, although the magnitude of this evidence is not strong. These
      findings serve to alert dermatologists to remain attentive to these factors,
      among patients with psoriasis.

PMID- 24138075
TI  - Antiarrhythmic drug therapy for maintaining sinus rhythm early after pulmonary
      vein ablation in patients with symptomatic atrial fibrillation.
AB  - AIMS: The optimal pharmacological treatment for patients early after ablation of
      atrial fibrillation (AF) is still not clear. We analyzed if concomitant
      antiarrhythmic drug (AAD) therapy significantly alters early recurrence of
      AF/atrial tachycardia (AT) following pulmonary vein ablation (PVA). METHODS: For
      the first 2 months after PVA, 274 patients (age 62 +/- 10 years; 66% male) were
      individually scheduled for concomitant treatment with beta-adrenergic blocking
      agents (BB) or AAD therapy. Primary endpoint of this study was a composite of (1)
      AF/AT lasting more than 30 seconds; (2) symptomatic AF/AT recurrence requiring
      intervention; or (3) intolerance to the antiarrhythmic agent given. Univariate
      and multivariate analysis was performed to evaluate predictors for successful AAD
      therapy. RESULTS: Early after PVA, patients were treated with BB (n = 89),
      flecainide (n = 99), sotalol (n = 37), dronedarone (n = 29), or amiodarone (n =
      115). Ninety-five patients received a combination of AAD therapy and BB. A total
      of 369 observation periods were analyzed. Over the first 2 months following PVA,
      AF/AT recurrences were found in 42% of patients. No significant difference
      regarding freedom from AF/AT recurrence with regard to different drug therapies
      was observed (P = 0.769). In multivariate analysis, none of the parameters were
      significant to predict success of AAD therapy. In nine observations, AAD therapy
      was terminated due to side effects presumably related to the respective agent.
      CONCLUSIONS: Following PVA, AAD therapy is not superior to BB treatment for the
      prevention of early atrial arrhythmias. Furthermore and confirmed by multivariate
      analysis, no drug was superior to another regarding the maintenance of sinus
      rhythm.

PMID- 24138076
TI  - A chemodosimeter for the ratiometric detection of hydrazine based on return of
      ESIPT and its application in live-cell imaging.
AB  - A probe based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) has been synthesized
      and used for the ratiometric detection of hydrazine. The probe is designed in
      such a way that the excited state intramolecular proton transfer (ESIPT) of the
      HBT moiety gets blocked. The chemodosimetric approach of hydrazine to the probe
      results in the recovery of the ESIPT by removal of a free HBT moiety through
      subsequent substitution, cyclization, and elimination processes. The probe is
      successfully demonstrated to enable the detection of hydrazine in live cells. 

PMID- 24138078
TI  - A focused review of the role of ketone bodies in health and disease.
AB  - Ketone bodies are produced in the liver and are utilized in other tissues in the
      body as an energy source when hypoglycemia occurs in the body. There are three
      ketone bodies: acetoacetate, beta hydroxy butyrate, and acetone. Ketone bodies
      are usually present in the blood, and their level increases during fasting and
      starvation. They are also found in the blood of neonates and pregnant women. In
      diabetic ketoacidosis, high levels of ketone bodies are produced in response to
      low insulin levels and high levels of counter-regulatory hormones.

PMID- 24138079
TI  - 8-Quinolinolato gallium complexes: iso-selective initiators for rac-lactide
      polymerization.
AB  - The synthesis and characterization of a series of 8-quinolinolato gallium
      complexes is presented, and the complexes are analogous to a series of aluminum
      complexes previously reported. The complexes have been shown to be active
      initiators for the ring-opening polymerization of rac-lactide. High degrees of
      polymerization control are demonstrated, as exemplified by the linear evolution
      of molecular weight as the polymerization progresses, narrow polydispersity
      indices, and molecular weights corresponding to those predicted on the basis of
      initiator concentration. Some of the initiators show iso-selective polymerization
      of rac-lactide, with Pi = 0.70. The polymerization rates have been monitored, and
      the pseudo first-order rate constants are compared to those of analogous aluminum
      compounds. The 8-quinolinolato gallium initiators show rates approximately 3
      times higher than those of the series of aluminum compounds, while maintaining
      equivalently high iso-selectivity (Pi = 0.70) and polymerization control. 

PMID- 24138077
TI  - Novel vasocontractile role of the P2Y14 receptor: characterization of its
      signalling in porcine isolated pancreatic arteries.
AB  - BACKGROUND AND PURPOSE: The P2Y14 receptor is the newest member of the P2Y
      receptor family; it is G(i/o) protein-coupled and is activated by UDP and
      selectively by UDP-glucose and MRS2690 (2-thiouridine-5'-diphosphoglucose) (7-10
      fold more potent than UDP-glucose). This study investigated whether P2Y14
      receptors were functionally expressed in porcine isolated pancreatic arteries.
      EXPERIMENTAL APPROACH: Pancreatic arteries were prepared for isometric tension
      recording and UDP-glucose, UDP and MRS2690 were applied cumulatively after
      preconstriction with U46619, a TxA2 mimetic. Levels of phosphorylated myosin
      light chain 2 (MLC2) were assessed with Western blotting. cAMP concentrations
      were assessed using a competitive enzyme immunoassay kit. KEY RESULTS:
      Concentration-dependent contractions with a rank order of potency of MRS2690 (10
      fold) > UDP-glucose >= UDP were recorded. These contractions were reduced by PPTN
      {4-[4-(piperidin-4-yl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid}, a
      selective antagonist of P2Y14 receptors, which did not affect responses to UTP.
      Contraction to UDP-glucose was not affected by MRS2578, a P2Y6 receptor selective
      antagonist. Raising cAMP levels and forskolin, in the presence of U46619,
      enhanced contractions to UDP-glucose. In addition, UDP-glucose and MRS2690
      inhibited forskolin-stimulated cAMP levels. Removal of the endothelium and
      inhibition of endothelium-derived contractile agents (TxA2, PGF(2alpha) and
      endothelin-1) inhibited contractions to UDP glucose. Y-27632, nifedipine and
      thapsigargin also reduced contractions to the agonists. UDP-glucose and MRS2690
      increased MLC2 phosphorylation, which was blocked by PPTN. CONCLUSIONS AND
      IMPLICATIONS: P2Y14 receptors play a novel vasocontractile role in porcine
      pancreatic arteries, mediating contraction via cAMP-dependent mechanisms,
      elevation of intracellular Ca2+ levels, activation of RhoA/ROCK signalling and
      MLC2, along with release of TxA2, PGF(2alpha) and endothelin-1.

PMID- 24138080
TI  - Epidemiology and etiology characteristics of foodborne outbreaks caused by Vibrio
      parahaemolyticus during 2008-2010 in Guangdong province, China.
AB  - Vibrio parahaemolyticus infection has been considered the leading cause of
      bacterial illnesses mainly associated with seafood consumption in Guangdong
      province in China. In this study, epidemiological and etiological characteristics
      of 36 V. parahaemolyticus outbreaks that occurred from 2008 to 2010 in Guangdong
      province were analyzed; 284 strains involved were characterized by serotyping;
      virulence genes and 66 strains from four outbreaks therein were subtyped by
      pulsed-field gel electrophoresis (PFGE). Epidemiological evidence showed that 36%
      (13/36) of outbreaks were caused by food contamination, of which 84.6 % (11/13)
      were related to salted food, including viscera of pigs and cattle, meat, and
      vegetable salad. It was also indicated that 88.9% (32/36) of V. parahaemolyticus
      outbreaks appeared from June to September, 44.4% (16/36) of which occurred in
      canteens as well as 41.7% (15/36) in restaurants. As for the etiology, 31%
      (11/36) of outbreaks were caused by single serovar of strains, while 69% (25/36)
      were caused by multiserovars; O3:K6, O4:K8, O1:Kut, and O2:K3 were the dominant
      serovars. Among the 284 strains, 98.8% (254/257) of strains from patients were
      tdh-present and trh-absent, whereas 37.0% (10/27) from food were tdh-present.
      Cluster analysis of PFGE patterns demonstrated that strains in the same outbreak
      with identical serovar seemed to be diversified, whereas strains with various
      serovars could be closely related genetically. Moreover, cross-contamination
      between salted food and seafood was first confirmed by molecular subtyping in
      Guangdong, revealing that salted food might be a vital risk factor associated
      with V. parahaemolyticus outbreaks.

PMID- 24138081
TI  - Meta-analysis on the effect of mental imagery on motor recovery of the hemiplegic
      upper extremity function.
AB  - BACKGROUND/AIM: Studies have shown that mental imagery can enhance relearning and
      generalisation of function after stroke. The aim of this meta-analysis was to
      evaluate evidence on the effects of mental imagery on motor recovery of the
      hemiplegic upper extremities after stroke. METHODS: A comprehensive data base
      search of the literature up to December 2012 was performed using PubMed, EBSCO
      host (Academic Search Premier, CINAHL and Educational Resource Information
      Center), PsycINFO, Medline, and ISI Web of Knowledge (Science Citation Index and
      Social Sciences Citation Index). Randomised clinical trials or controlled
      clinical trials that included mental imagery for improving upper extremity motor
      function for stroke patients were located. Relevant articles were critically
      reviewed and methodological quality was evaluated using the PEDro Scale, and
      study results synthesised. RESULTS: Five randomised clinical trials and one
      controlled clinical trial met the inclusion criteria. Five of the six studies
      yielded positive findings in favour of mental imagery. Quantitative analysis
      showed a significant difference in the Action Research Arm Test (overall effect:
      Z=6.75; P<<0.001). CONCLUSION: Review of the literature revealed a trend in
      support of the use of motor imagery for upper extremity motor rehabilitation
      after stroke. Mental imagery could be a viable intervention for stroke patients
      given its benefits of being safe, cost-effective and rendering multiple and
      unlimited practice opportunities. It is recommended that researchers incorporate
      imaging techniques into clinical studies so that the mechanism whereby mental
      imagery mediates motor recovery or neural adaptation for people with stroke can
      be better understood.

PMID- 24138082
TI  - Healthy aging in relation to chronic pain and quality of life in Europe.
AB  - OBJECTIVE: To undertake a review of the most recent data on the relationship
      between quality of life (QoL) and chronic pain, as a basis for discussions about
      healthy aging in Europe. METHOD: A search was conducted to obtain studies on the
      relationship between pain severity and QoL and intervention studies reporting
      both QoL and pain severity in those with chronic pain in Europe. Medline and
      Embase were searched for observational studies and systematic reviews from 2009
      to 2011. Four further databases were searched for systematic reviews and guidance
      from 2005 to 2011. Update searches for observational studies and systematic
      reviews for the period November 2011 to January 2013 were performed on Medline
      and Embase. RESULTS: We identified 8 observational studies and 1 systematic
      review that generally showed a statistically significant relationship between
      pain severity and QoL. We identified 5 systematic reviews of interventions in
      chronic pain that summarized both pain and QoL data that generally showed both a
      statistically significant reduction in pain and statistically significant
      increase in QoL. CONCLUSION: There is strong evidence of a correlation between
      pain severity and QoL. There is some evidence that treatment in chronic pain
      patients can reduce pain and simultaneously improve QoL. Prevention and treatment
      of chronic pain may be of significant help in reaching the aim to increase the
      healthy lifespan.

PMID- 24138084
TI  - Immobilization of gold nanorods onto electrospun polycaprolactone fibers via
      polyelectrolyte decoration--a 3D SERS substrate.
AB  - We report the fabrication of a homogeneous and highly dense gold nanorod (AuNR)
      assembly on electrospun polycaprolactone (PCL) fibers using electrostatic
      interaction as the driving force. Specifically, decoration of a poly(sodium 4
      styrenesulfonate) (PSS) layer onto the AuNRs imposed negative charges on the
      nanorod surface, and the interactions between PSS and the AuNRs were investigated
      using attenuated total reflection Fourier transform infrared spectroscopy (ATR
      FTIR). Positive charges on the PCL fibrous substrate were established via
      polyelectrolyte layer-by-layer deposition, which was investigated using multiple
      characterization techniques. Driven by the attractive electrostatic interaction,
      immobilization of AuNRs on the PCL fibers was initiated upon substrate immersion,
      and the kinetics of the immobilization process were studied using UV-vis
      spectroscopy. Electron microscopy characterization of the AuNR/PCL nanocomposite
      fibers reveals a uniform AuNR coating on the fiber surface with the immobilized
      AuNR density being high enough to provide full surface coverage. By using both 4
      mercaptopyridine and Rhodamine 6G as probe molecules, the performance of the
      AuNR/PCL fibrous mesh as a three-dimensional (3D) surface-enhanced Raman
      scattering (SERS) substrate was investigated. The nanocomposite fibers allowed
      detection at concentrations as low as 10(-7) M of the probe molecule in solution
      and exhibited excellent reproducibility in the SERS measurements. In addition, a
      comparison between the 3D AuNR/PCL fibrous mesh and a 2D AuNR/PCL film reveals
      that the enhanced surface area in the 3D substrate effectively improved the SERS
      performance with a 6-fold increase in the Raman intensity. 

PMID- 24138083
TI  - Xylazine-induced reduction of tissue sensitivity to insulin leads to acute
      hyperglycemia in diabetic and normoglycemic monkeys.
AB  - BACKGROUND: The alpha2-adrenoceptor agonist xylazine as an anesthetic has been
      widely used either alone or in combination with other anesthetics, such as
      ketamine, in veterinary clinic and research. In the last decade xylazine has been
      used in drug abusers in certain geographic area. This study investigated the
      effects of xylazine on blood glucose level and insulin secretion in normoglycemic
      and insulin-dependent diabetic monkeys. METHODS: Both adult cynomolgus (n = 10)
      and rhesus (n = 8) monkeys with either sex were used in the study. Xylazine (1-2
      mg/kg) was administrated intramuscularly. Blood glucose, insulin, glucagon and
      glucagon-like peptide 1 in overnight-fasted monkeys were measured immediately
      before and after xylazine administration. The hyperinsulinemic-euglycemic clamp
      method was used in the study for assessing the potential mechanism of xylazine
      induced hyperglycemia. RESULTS: Xylazine administration increased the blood
      glucose levels from 58 +/- 3 to 108 +/- 12 mg/dL in normoglycemic (n = 5, p <
      0.01) and from 158 +/- 9 to 221 +/- 13 mg/dL in insulin-dependent diabetic (n =
      5, p < 0.01) monkeys and was not accompanied by any significant changes in blood
      insulin, glucagon, and glucagon-like peptide-1. Xylazine-induced hyperglycemia
      occurred within 10 min and reached the peak at 35 min after injection. Xylazine
      induced hyperglycemia declined slowly in diabetic animals. The alpha2
      adrenoceptor antagonist yohimbine was administrated to bring down the elevated
      glucose level to the pre-xylazine one in 4 out of 5 diabetic animals. To assess
      the potential mechanism, the hyperinsulinemic-euglycemic clamp was used to
      maintain a nearly saturated and constant insulin level for minimizing endogenous
      insulin glucoregulation. Xylazine administration decreased glucose infusion rate,
      from 14.3 +/- 1.4 to 8.3 +/- 0.8 mg/min/kg (n = 6, p < 0.01) in normoglycemic
      rhesus monkeys, which indicates that the glucose metabolic rate (M rate) was
      decreased by xylazine. In addition, after clamping blood glucose level in a range
      of 55 to 75 mg/dL for 40 min with constant glucose infusion, xylazine
      administration still increased blood glucose concentration. CONCLUSIONS: We
      conclude that xylazine administration induces hyperglycemia in normoglycemic and
      insulin-dependent diabetic monkeys potentially via stimulation of alpha2
      adrenoceptors and then reducing tissue sensitivity to insulin and glucose uptake.

PMID- 24138085
TI  - Multifunctional nanoplatforms for targeted multidrug-resistant-bacteria
      theranostic applications.
AB  - The emergence of multidrug-resistant-bacteria (MDRB) infection poses a major
      burden to modern healthcare. Early detection in the bloodstream and a new
      strategy development for MDRB infection treatment without antibiotics are
      clinically significant to save millions of lives every year. To tackle the MDRB
      challenge, the current manuscript reports the design of "multifunctional
      nanoplatforms" consisting of a magnetic core-plasmonic shell nanoparticle, a
      methylene blue-bound aptamer, and an MDRB Salmonella DT104 specific antibody. The
      reported "multifunctional nanoplatform" is capable of targeted separation from a
      blood sample and sensing and multimodal therapeutic killing of MDRB. Experimental
      data using an MDRB-infected whole-blood sample show that nanoplatforms can be
      used for selective magnetic separation and fluorescence imaging. In vitro light
      triggered photodestruction of MDRB, using combined photodynamic and photothermal
      treatment, shows that the multimodal treatment regime can enhance MDRB killing
      significantly. We discussed the possible mechanisms on combined synergistic
      therapy for killing MDRB. The "multifunctional nanoplatform" reported in this
      manuscript has great potential for the imaging and combined therapy of MDRB in
      clinical settings. 

PMID- 24138086
TI  - Human nephrotoxicity prediction models for three types of kidney injury based on
      data sets of pharmacological compounds and their metabolites.
AB  - The kidney is the most important organ for the excretion of pharmaceuticals and
      their metabolites. Among the complex structures of the kidney, the proximal
      tubule and renal interstitium are major targets of nephrotoxins. Despite its
      importance, there are only a few in silico models for predicting human
      nephrotoxicity for drug candidates. Here, we present quantitative structure
      activity relationship (QSAR) models for three common patterns of drug-induced
      kidney injury, i.e., tubular necrosis, interstitial nephritis, and tubulo
      interstitial nephritis. A support vector machine (SVM) was used to build the
      binary classification models of nephrotoxin versus non-nephrotoxin with eight
      fingerprint descriptors. To build the models, we constructed two types of data
      sets, i.e., parent compounds of pharmaceuticals (251 nephrotoxins and 387 non
      nephrotoxins) and their major urinary metabolites (307 nephrotoxins and 233 non
      nephrotoxins). Information on the nephrotoxicity of the pharmaceuticals was taken
      from clinical trial and postmarketing safety data. Though the mechanisms of
      nephrotoxicity are very complex, by using the metabolite information, the
      predictive accuracies of the best models for each type of kidney injury were
      better than 83% for external validation sets. Software to predict nephrotoxicity
      is freely available from our Web site at http://bmdrc.org/DemoDownload . 

PMID- 24138087
TI  - Concurrent observation of bulk and protein hydration water by spin-label ESR
      under nanoconfinement.
AB  - Under nanoconfinement the formation of crystalline ice is suppressed, allowing
      the study of water dynamics at subfreezing temperatures. Here we report a
      temperature-dependent investigation (170-260 K) of the behavior of hydration
      water under nanoconfinement by ESR techniques. A 26-mer-long peptide and the Bax
      protein are studied. This study provides site-specific information about the
      different local hydrations concurrently present in the protein/peptide solution,
      enabling a decent comparison of the hydration molecules-those that are buried
      inside, in contact with, and detached from the protein surface. Such a comparison
      is not possible without employing ESR under nanoconfinement. Though the confined
      bulk and surface hydrations behave differently, they both possess a transition
      similar to the reported fragile-to-strong crossover transition around 220 K. On
      the contrary, this transition is absent for the hydration near the buried sites
      of the protein. The activation energy determined under nanoconfinement is found
      to be lower in surface hydration than in bulk hydration. The protein structural
      flexibility, derived from the interspin distance distributions P(r) at different
      temperatures, is obtained by dipolar ESR spectroscopy. The P(r) result
      demonstrates that the structural flexibility is strongly correlated with the
      transition in the surface water, corroborating the origin of the protein
      dynamical transition at subfreezing temperatures. 

PMID- 24138088
TI  - Genomics and museum specimens.
AB  - Nearly 25 years ago, Allan Wilson and colleagues isolated DNA sequences from
      museum specimens of kangaroo rats (Dipodomys panamintinus) and compared these
      sequences with those from freshly collected animals (Thomas et al. 1990). The
      museum specimens had been collected up to 78 years earlier, so the two samples
      provided a direct temporal comparison of patterns of genetic variation. This was
      not the first time DNA sequences had been isolated from preserved material, but
      it was the first time it had been carried out with a population sample.
      Population geneticists often try to make inferences about the influence of
      historical processes such as selection, drift, mutation and migration on patterns
      of genetic variation in the present. The work of Wilson and colleagues was
      important in part because it suggested a way in which population geneticists
      could actually study genetic change in natural populations through time, much the
      same way that experimentalists can do with artificial populations in the
      laboratory. Indeed, the work of Thomas et al. (1990) spawned dozens of studies in
      which museum specimens were used to compare historical and present-day genetic
      diversity (reviewed in Wandeler et al. 2007). All of these studies, however, were
      limited by the same fundamental problem: old DNA is degraded into short
      fragments. As a consequence, these studies mostly involved PCR amplification of
      short templates, usually short stretches of mitochondrial DNA or microsatellites.
      In this issue, Bi et al. (2013) report a breakthrough that should open the door
      to studies of genomic variation in museum specimens. They used target enrichment
      (exon capture) and next-generation (Illumina) sequencing to compare patterns of
      genetic variation in historic and present-day population samples of alpine
      chipmunks (Tamias alpinus) (Fig. 1). The historic samples came from specimens
      collected in 1915, so the temporal span of this comparison is nearly 100 years.

PMID- 24138089
TI  - Impact of mindfulness training on attentional control and anger regulation
      processes for psychotherapists in training.
AB  - OBJECTIVES: Little empirical literature focuses on psychotherapists' cultivation
      of internal states of mind necessary for controlling attention and responding
      empathically to the client. We explore the effects of mindfulness training on
      emotional and attentional measures in Spanish resident intern psychiatrists and
      clinical psychologists. METHOD: One hundred and three residents were assigned to
      an experimental group (n = 60) that completed an 8-week mindfulness training
      versus a wait-list control group (n = 43). We evaluated emotional variables
      (sadness, anxiety, and anger, using standard instruments), state of mindfulness
      (using the Mindfulness Awareness Attention Scale), and attentional control
      variables using objective measures such as a continuous performance task and the
      Stroop task before and after mindfulness training. RESULTS: Our study provides
      data that suggest that mindfulness training significantly improves measures of
      trait anger and attentional control. CONCLUSIONS: Further research is needed to
      replicate these findings, explore the effects of mindfulness training on other
      aspects of emotional regulation and cognition, and evaluate the impact of these
      effects within clinical situations.

PMID- 24138090
TI  - Adult granulosa cell tumour-like areas occurring in ovarian epithelial neoplasms:
      report of a case series with investigation of FOXL2 mutation status.
AB  - AIMS: To look for FOXL2 mutation in rare ovarian epithelial lesions showing
      stromal components with morphological features of adult granulosa cell tumour
      (AGCT). METHODS AND RESULTS: We report the 402C->G FOXL2 mutation status in five
      epithelial ovarian lesions in women aged 45-77 years showing stromal
      proliferations that were morphologically indistinguishable from AGCT. The lesions
      were mucinous cystadenoma, mixed epithelial cystadenoma, endometriotic cyst,
      mucinous borderline tumour (intestinal type), and mucinous carcinoma. In one
      case, the AGCT component formed a discrete nodule, and in the others it was
      distributed within the septa and cyst walls. FOXL2 mutation was present in two
      cases and absent in three cases. One mutation-positive case showed an AGCT nodule
      abutting a mucinous borderline tumour, interpreted as a collision tumour. The
      other positive case had an AGCT component within the septa of a mucinous
      carcinoma, and both components are likely to be neoplastic. In the three cases
      without FOXL2 mutation, the stromal component most likely represents a non
      neoplastic AGCT-like proliferation. CONCLUSIONS: Areas typical of AGCT are rarely
      associated with epithelial ovarian lesions. These are heterogeneous and likely to
      be truly neoplastic in only a subset of cases. FOXL2 mutation testing may be
      useful in confirming a true neoplastic AGCT component.

PMID- 24138092
TI  - A rare case of nonobstructive membrane of the left atrial appendage.
AB  - The left atrial appendage (LAA) is a blind-ending, complex structure distinct
      from the body of the left atrium and is sometimes regarded as a minor extension
      of the atrium. However, it should routinely be evaluated as part of a
      transesophageal echocardiographic examination. In this study we describe the
      presence of a nonobstructive membrane traversing the cavity of the LAA, found
      incidentally on transesophageal echocardiography. 

PMID- 24138091
TI  - Involvement of a membrane potassium channel in heparan sulphate-induced
      activation of macrophages.
AB  - Increasing evidence has demonstrated that Toll-like receptor 4 (TLR4) -mediated
      systemic inflammatory response syndrome accompanied by multiple organ failure, is
      one of the most common causes of death in patients with severe acute
      pancreatitis. Recent reports have revealed that heparan sulphate (HS)
      proteoglycan, a component of extracellular matrices, potentiates the activation
      of intracellular pro-inflammatory responses via TLR4, contributing to the
      aggravation of acute pancreatitis. However, little is known about the
      participants in the HS/TLR4-mediated inflammatory cascades. Our previous work
      provided a clue that a membrane potassium channel (MaxiK) is responsible for HS
      induced production of inflammatory cytokines. Therefore, in this report we
      attempted to reveal the roles of MaxiK in the activation of macrophages
      stimulated by HS. Our results showed that incubation of RAW264.7 cells with HS up
      regulated MaxiK and TLR4 expression levels. HS could also activate MaxiK channels
      to promote the efflux of potassium ions from cells, as measured by the elevated
      activity of caspase-1, whereas this was significantly abolished by treatment with
      paxilline, a specific blocker of the MaxiK channel. Moreover, it was found that
      paxilline substantially inhibited HS-induced activation of several different
      transcription factors in macrophages, including nuclear factor-kappaB, p38 and
      interferon regulatory factor-3, followed by decreased production of tumour
      necrosis factor-alpha and interferon-beta. Taken together, our investigation
      provides evidence that the HS/TLR4-mediated intracellular inflammatory cascade
      depends on the activation of MaxiK, which may offer an important opportunity for
      a new approach in therapeutic strategies of severe acute pancreatitis.

PMID- 24138093
TI  - Assessment of pollen reward and pollen availability in Solanum stramoniifolium
      and Solanum paniculatum for buzz-pollinating carpenter bees.
AB  - The two widespread tropical Solanum species S. paniculatum and S. stramoniifolium
      are highly dependent on the visits of large bees that pollinate the flowers while
      buzzing them. Both Solanum species do not offer nectar reward; the rewarding of
      bees is thus solely dependent on the availability of pollen. Flower visitors are
      unable to visually assess the amount of pollen, because the pollen is hidden in
      poricidal anthers. In this study we ask whether and how the amount of pollen
      determines the attractiveness of flowers for bees. The number of pollen grains in
      anthers of S. stramoniifolium was seven times higher than in S. paniculatum. By
      contrast, the handling time per five flowers for carpenter bees visiting S.
      paniculatum was 3.5 times shorter than of those visiting S. stramoniifolium. As a
      result foraging carpenter bees collected a similar number of pollen grains per
      unit time on flowers of both species. Experimental manipulation of pollen
      availability by gluing the anther pores showed that the carpenter bees were
      unable to detect the availability of pollen by means of chemical cues before
      landing and without buzzing. Our study shows that the efficiency of pollen
      collecting on S. paniculatum is based on large inflorescences with short between
      flower search times and short handling time of individual flowers, whereas that
      of S. stramoniifolium relies on a large amount of pollen per flower.
      Interestingly, large carpenter bees are able to adjust their foraging behaviour
      to drastically different strategies of pollen reward in otherwise very similar
      plant species.

PMID- 24138094
TI  - Collecting and assessing human lactate dehydrogenase-A conformations for
      structure-based virtual screening.
AB  - Human lactate dehydrogenase-A (LDHA) is emerging as a promising anticancer
      target. Up to now, structure-based investigations for identifying inhibitors of
      this enzyme have not explicitly accounted for active site flexibility. In the
      present study, by combining replica exchange molecular dynamics with network and
      cluster analyses, we identified reliable LDHA conformations for structure-based
      ligand design. The selected conformations were challenged and validated by
      retrospective virtual screening simulations. 

PMID- 24138095
TI  - C.57 C > T Mutation in MIR 184 is Responsible for Congenital Cataracts and
      Corneal Abnormalities in a Five-generation Family from Galicia, Spain.
AB  - A c.57 C > T mutation in the seed region of MIR184 located at the 15q25.1
      chromosomal region has been independently associated with autosomal dominant
      keratoconus with early-onset anterior polar cataract in the Northern Irish family
      and with autosomal dominant EDICT (Endothelial Dystrophy, Iris hypoplasia,
      Congenital cataracts, and stromal Thinning) syndrome. In this study we report a
      five-generation family originating in Galicia, Spain with early onset cataracts
      and variable corneal abnormalities which include non-ectatic corneal thinning and
      severe early-onset keratoconus. We identified a heterozygous c.57 C > T mutation
      in miR-184 in the proband and two additional affected relatives on the maternal
      side. This finding represents a third independent occurrence of this mutation in
      familiar ocular disease thus strengthening the link between miR-184 abnormalities
      and inherited eye defects.

PMID- 24138096
TI  - Substance use among victimized women on probation and parole.
AB  - Victimized women within the criminal justice system are an important group and
      understanding their substance use is critical. Substance use was examined among
      406 victimized women on probation and parole in an urban community from 2010 to
      2013. Ninety-three percent reported lifetime use of an illicit substance, whereas
      58% and 45% reported use of at least one illicit substance in the past 2 years
      and 12 months, respectively. Among probationers, having been in a controlled
      environment was associated with a higher prevalence of illicit substance use as
      compared to parolees. Implications for practice, policy, and future research are
      discussed. 

PMID- 24138097
TI  - Improving medication adherence in chronic obstructive pulmonary disease: a
      systematic review.
AB  - Adherence to medication among individuals with chronic obstructive pulmonary
      disease (COPD) is suboptimal and has negative impacts on survival and health care
      costs. No systematic review has examined the effectiveness of interventions
      designed to improve medication adherence. Electronic databases Medline and
      Cochrane were searched using a combination of MeSH and keywords. Eligible studies
      were interventions with a primary or secondary aim to improve medication
      adherence among individuals with COPD published in English. Included studies were
      assessed for methodological quality using the Effective Practice and Organisation
      of Care (EPOC) criteria. Of the 1,186 papers identified, seven studies met
      inclusion criteria. Methodological quality of the studies was variable. Five
      studies identified effective interventions. Strategies included: brief
      counselling; monitoring and feedback about inhaler use through electronic
      medication delivery devices; and multi-component interventions consisting of self
      management and care co-ordination delivered by pharmacists and primary care
      teams. Further research is needed to establish the most effective and cost
      effective interventions. Special attention should be given to increasing patient
      sample size and using a common measure of adherence to overcome methodological
      limitations. Interventions that involve caregivers and target the healthcare
      provider as well as the patient should be further explored. 

PMID- 24138098
TI  - Is self-esteem a cause or consequence of social support? A 4-year longitudinal
      study.
AB  - Considerable research has been devoted to examining the relations between self
      esteem and social support. However, the exact nature and direction of these
      relations are not well understood. Measures of self-esteem, and social support
      quantity and quality were administered to 961 adolescents across five yearly time
      points (M(age) = 13.41 years). Structural equation modeling (SEM) was utilized to
      test between a self-esteem antecedent model (self-esteem precedes changes in
      social support), self-esteem consequence model (social support precedes change in
      self-esteem), and a reciprocal influence model. Self-esteem reliably predicted
      increasing levels of social support quality and network size across time. In
      contrast, the consequence model was not supported. The implications of this for
      helping adolescents to develop higher quality social support structures are
      discussed.

PMID- 24138099
TI  - Osteogenic differentiation of human periodontal ligament cells after transfection
      with recombinant lentiviral vector containing follicular dendritic cell secreted
      protein.
AB  - BACKGROUND AND OBJECTIVE: Follicular dendritic cell secreted protein (FDC-SP),
      has been identified in human periodontal ligament (PDL) in a recent study. It is
      suggested that the expression of FDC-SP might be associated with the osteogenic
      differentiation and mineralization of human periodontal ligament cells (hPDLCs).
      However, the intrinsic mechanism regarding this is still unclear. The aim of this
      study was to establish hPDLCs with safe and efficient overexpression of FDC-SP
      and to elucidate the influence of FDC-SP transfection on hPDLC osteogenesis in
      periodontal regeneration. MATERIAL AND METHODS: We first applied a recombinant
      lentiviral vector containing FDC-SP to transfect hPDLCs via different
      multiplicity of infection (MOI) levels (1, 10, 20, 50 and 100). Western blot was
      performed to confirm the expression of FDC-SP. MTT assay was employed to evaluate
      the proliferation status of transfected cells. Then, the extent of osteogenic
      differentiation was investigated by simultaneous monitoring of alkaline
      phosphatase (ALP) activity assessment, immunofluorescent staining, the expression
      patterns of osteoblastic markers and mineralization staining. RESULTS: We found
      that hPDLCs transfected via MOI 20, 50 and 100 exhibited expression of FDC-SP
      protein compared with MOI 1 and 10. There was no significant effect of FDC-SP
      transfection (at different MOI levels of 1, 10 and 20) on the proliferation of
      hPDLCs, whereas higher MOI levels (50 and 100) inhibited cell proliferation
      ability. In addition, ALP activity decreased significantly in FDC-SP-transfected
      hPDLCs at day 7. When stained with alizarin red, cells overexpressing FDC-SP
      formed less mineralized nodules at 21 d post-induction of differentiation,
      compared with the control cultures. Osteogenic inhibition was also confirmed by
      ALP immunostaining. Moreover, mRNA expression levels of osteoblastic markers
      decreased after FDC-SP transfection, which were in accordance with western blot
      results. CONCLUSION: Our data suggest that MOI 20 is optimal to transfect hPDLCs,
      which achieves safe and efficient overexpression of FDC-SP in transfected cells.
      Moreover, FDC-SP overexpression inhibits osteogenic differentiation of hPDLCs.
      The present study contributes to a better understanding of the biological
      functions governing FDC-SP-induced hPDLC differentiation.

PMID- 24138100
TI  - Premature loss of primary anterior teeth due to trauma--potential short- and long
      term sequelae.
AB  - Traumatic dental injuries (TDIs) can result in the premature loss of primary
      anterior teeth due to an immediate avulsion, extraction later after the injury
      because of poor prognosis or late complications, or early exfoliation. There are
      a number of potential considerations or sequelae as a result of this premature
      loss that have been cited in the dental literature, which include esthetics,
      quality of life, eating, speech development, arch integrity (space loss),
      development and eruption of the permanent successors, and development of oral
      habits. This article provides a comprehensive review of the dental literature on
      the possible consequences of premature loss of maxillary primary incisors
      following TDI. 

PMID- 24138101
TI  - Tuning amidoximate to enhance uranyl binding: a density functional theory study.
AB  - Amidoxime functionalized sorbents have shown great promise in extracting uranium
      from seawater, though the rationale for this affinity is not apparent. To enhance
      binding by amidoxime and to develop more selective sorbents, a detailed
      understanding of the electronic structure is necessary. This study investigates
      the electronic effects of amidoximate ligands bound to the uranyl cation,
      UO2(2+). Density functional theory calculations have been performed on a series
      of uranyl-amidoximate derivatives to investigate their structural, electronic,
      and thermochemical properties. The computational findings are in good agreement
      with available experimental data, with average error in bond length below 0.07 A
      for all systems. Binding strength was observed to be directly related to electron
      donation, as evidenced by the plot of log(K/K0) vs the Hammett constant
      (sigmapara) of the substituent adjacent to the oximate function. From this
      observation, we propose and investigate two new imidazole-derived oximes, both of
      which possess greater binding strength than amidoximate derivatives. 

PMID- 24138102
TI  - Polyclusters and substitution effects in the Na-Au-Ga system: remarkable sodium
      bonding characteristics in polar intermetallics.
AB  - A systematic exploration of Na- and Au-poor parts of the Na-Au-Ga system (less
      than 15 at. % Na or Au) uncovered several compounds with novel structural
      features that are unusual for the rest of the system. Four ternary compounds
      Na1.00(3)Au0.18Ga1.82(1) (I), NaAu2Ga4 (II), Na5Au10Ga16 (III), and NaAu4Ga2 (IV)
      have been synthesized and structurally characterized by single crystal X-ray
      diffraction: Na1.00(3)Au0.18Ga1.82(1)(I, P6/mmm, a = 15.181(2), c =9.129(2)A, Z =
      30); NaAu2Ga4 (II, Pnma, a = 16.733(3), b = 4.3330(9), c =7.358(3) A, Z = 4);
      Na5Au10Ga16 (III, P6(3)/m, a = 10.754(2), c =11.457(2) A, Z = 2); and NaAu4Ga2
      (IV, P2(1)/c, a = 8.292(2), b = 7.361(1), c =9.220(2)A, beta = 116.15(3), Z = 4).
      Compound I lies between the large family of Bergman-related compounds and Na-poor
      Zintl-type compounds and exhibits a clathrate-like structure containing
      icosahedral clusters similar to those in cubic 1/1 approximants, as well as
      tunnels with highly disordered cation positions and fused Na-centered clusters.
      Structures II, III, and IV are built of polyanionic networks and clusters that
      generate novel tunnels in each that contain isolated, ordered Na atoms. Tight
      binding electronic structure calculations using linear muffin-tin-orbital (LMTO)
      methods on II, III, IV and an idealized model of I show that all are metallic
      with evident pseudogaps at the Fermi levels. The integrated crystal orbital
      Hamilton populations for II-IV are typically dominated by Au-Ga, Ga-Ga, and Au-Au
      bonding, although Na-Au and Na-Ga contributions are also significant. Sodium's
      involvement into such covalency is consistent with that recently reported in Na
      Au-M (M = Ga, Ge, Sn, Zn, and Cd) phases.

PMID- 24138103
TI  - Effects of neutral endopeptidase (neprilysin) inhibition on the response to other
      vasoactive peptides in small human resistance arteries: studies with thiorphan
      and omapatrilat.
AB  - PURPOSE: New compounds with neprilysin or neutral endopeptidase (NEP) inhibiting
      activity are under clinical investigation in heart failure and hypertension. We
      investigated the effect of NEP inhibition on the functional vasomotor responses
      to a range of vasoactive peptides in human blood vessels. METHODS: Small human
      resistance arteries from patients with coronary artery disease and preserved left
      ventricular systolic function were studied. Thiorphan (a NEP inhibitor) was
      compared with captopril (an ACE inhibitor) and omapatrilat (a dual NEP-ACE
      inhibitor) with regard to their effects on the response of human arteries to key
      vasoactive peptides. RESULTS: As expected, both captopril and omapatrilat (but
      not thiorphan) inhibited the vasoconstrictor effect of angiotensin I (maximal
      response [SEM]: 27 +/- 8% vehicle, 6 +/- 2% captopril, 39 +/- 10% thiorphan, 8 +/
      7% omapatrilat, P < 0.05). Thiorphan, captopril, and omapatrilat all enhanced
      the vasodilator response to bradykinin (all P < 0.01). Omapatrilat markedly
      augmented the vasodilator action of adrenomedullin (P < 0.05), whilst thiorphan
      and captopril did not. None of the three inhibitors studied affected the
      vasodilator action of c-type natriuretic peptide, calcitonin gene-related
      peptide, vasoactive intestinal polypeptide or substance P. CONCLUSIONS: NEP
      inhibition with thiorphan modestly augmented the vasodilator action of
      bradykinin, but did not potentiate the response to adrenomedullin; dual ACE and
      NEP inhibition with omapatrilat, as expected, markedly augmented the response to
      bradykinin and also potentiated the effect of adrenomedullin. Thiorphan weakly
      enhanced the vasoconstrictor response to angiotensin I. Neither omapatrilat nor
      thiorphan had any effect on the action of a range of other vasoactive peptides
      including CNP.

PMID- 24138105
TI  - A straightforward and highly diastereoselective access to functionalized
      monofluorinated cyclopropanes via a Michael initiated ring closure reaction.
AB  - The synthesis of highly functionalized monofluorinated cyclopropanes based on a
      Michael Initiated Ring Closure (MIRC) reaction has been developed. The addition
      of quaternary ammonium salts derived from ethyl bromofluoroacetate on a panel of
      electron deficient alkenes followed by cyclization gave rise to an efficient
      access to monofluorinated cyclopropanes with good yields and remarkable
      diastereoselectivity. 

PMID- 24138104
TI  - Translational issues in targeting brown adipose tissue thermogenesis for human
      obesity management.
AB  - The recent advancements in unraveling novel mechanisms that control the
      induction, (trans)differentiation, proliferation, and thermogenic activity and
      capacity of brown adipose tissue (BAT), together with the application of imaging
      techniques for human BAT visualization, have generated optimism that these
      advances will provide novel strategies for targeting BAT thermogenesis, leading
      to efficacious and safe obesity therapies. This paper first provides an overview
      of landmark events of the past few decades that have been driving the search for
      pharmaceutical and nutraceutical compounds that would increase BAT thermogenesis
      for obesity management. It then addresses issues about what could be expected
      from an ideal thermogenic antiobesity approach, in particular to what extent
      daily energy expenditure will need to increase in order to achieve long-term
      weight loss currently achievable only through bariatric surgery, and whether the
      human body will have enough thermogenic capacity to reach this target weight loss
      by future therapies focused on BAT. 

PMID- 24138106
TI  - Anthropometric measurements in infants conceived by assisted reproductive
      techniques versus spontaneous conception.
AB  - OBJECTIVE: To compare body length and head circumference at birth of neonates
      conceived after in vitro fertilization/intracytoplasmic injection (IVF/ICSI),
      ovarian stimulation alone (OSa) or by natural conception (NC). METHODS: A
      retrospective, cohort study of all singleton neonates conceived after fertility
      treatment and born at 38-40 gestational weeks in 2011 in a tertiary, university
      affiliated hospital. Pregnancy, delivery and neonatal data were obtained from the
      medical records. NC singleton neonates born at 38-40 weeks were selected to serve
      as controls. RESULTS: The sample included 81 IVF/ICSI neonates, 102 OSa neonates
      and 91 neonates after NC. Mean gestational age (GA) was 38.8 weeks. Gravidity and
      parity were significantly higher in the NC group. Mean neonatal length was 50.0
      +/- 2.1  cm in the IVF/ICSI group, 49.7 +/- 2.6 cm in the OSa group and 50.3 +/-
      2 cm in the NC group (p = 0.123). Corresponding mean head circumference was 34.4
      +/- 1.5, 34.2 +/- 1.8 and 34.5 +/- 1.2 cm (p = 0.287). Neither of these
      parameters was significantly different even after adjustment for GA at delivery
      and sex. CONCLUSIONS: Our study showed no significant difference in body length
      or head circumference at birth related to the mode of conception. Previously
      reported differences in anthropometric parameters in childhood may be related to
      other factors.

PMID- 24138108
TI  - Asymptomatic subjects with diabetes have a comparable risk of coronary artery
      disease to non-diabetic subjects presenting chest pain: a 4-year community-based
      prospective study.
AB  - BACKGROUND: Although diabetes mellitus is an important risk factor of coronary
      artery disease (CAD), routine screening for CAD is not recommended for
      asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk
      according to the presence or absence of diabetes mellitus. METHODS: We
      investigated the future CAD event rate in subjects with and without chest pain
      according to the presence or absence of diabetes in a prospective large-scale
      community-based study in Korea. RESULTS: Among 8,574 subjects (4,032 men and
      4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic
      subjects, respectively, reported newly developed CAD events during 4 years of
      follow-up. Although the presence of chest pain at baseline was also significantly
      associated with an increased risk of CAD of more than 2-fold in both non-diabetic
      and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic
      diabetic patients was not significantly different from that in non-diabetic
      subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 -
      1.998). CONCLUSIONS: The CAD event rate of asymptomatic subjects with diabetes
      was comparable to that of non-diabetic subjects reporting chest pain. Considering
      the high risk of CAD in asymptomatic diabetic patients, more clinical trials
      aimed at formulating strategies to screen asymptomatic diabetic subjects should
      be carried out.

PMID- 24138107
TI  - Underpinning the repurposing of anthracyclines towards colorectal cancer:
      assessment of topoisomerase II alpha gene copy number alterations in colorectal
      cancer.
AB  - OBJECTIVE. We propose a repurposing strategy where anthracyclines are
      reintroduced to a subgroup of patients with metastatic colorectal cancer with the
      highest likelihood of response. In breast cancer, DNA topoisomerase II alpha gene
      (TOP2A) alterations predict incremental benefit of anthracyclines, but this
      association has not been investigated in colorectal cancer. Frequency analysis of
      TOP2A gene alterations in colorectal cancer and the association with prognosis
      are evaluated and the challenges of using a TOP2A/CEN-17 FISH probe combination
      are addressed. MATERIAL AND METHODS. Formalin-fixed, paraffin-embedded material
      from 154 stage III colorectal cancer patients included in the RANX05 clinical
      trial was retrospectively assessed for TOP2A gene alterations using FISH. The
      TOP2A/CEN-17 ratio as well as the TOP2A gene copy number alone was used to define
      gene alterations and associations between gene status and outcomes were analyzed.
      RESULTS. TOP2A gene gain was a frequent finding with 9.8 % having a total of >=4
      TOP2A copies per cell. According to the TOP2A/CEN-17 ratio, 10.5 % had TOP2A gene
      gain. Polysomy or gain of the centromere region of chromosome-17 was not as
      frequent as reported in breast cancer. No prognostic characteristic of TOP2A was
      identified. CONCLUSION. TOP2A gene gain is present in numbers relevant to
      identify a subgroup of patients who may benefit from anthracycline therapy. Based
      on the present findings, we will initiate a prospective clinical trial designed
      to evaluate this hypothesis in patients with metastatic colorectal cancer who
      have failed 5-fluorouracil and oxaliplatin chemotherapy.

PMID- 24138109
TI  - Engineered stealth porous silicon nanoparticles via surface encapsulation of
      bovine serum albumin for prolonging blood circulation in vivo.
AB  - Luminescent porous silicon nanoparticles (PSiNPs) have been widely used as drug
      delivery. However, fast biodegradation and short blood circulation have been
      major challenges for their biomedical applications. Herein, bovine serum albumin
      was readily encapsulated onto alkyl-terminated PSiNPs surfaces via hydrophobic
      interaction, which could significantly improve their water-dispersibility and
      long-term stability under physiological conditions. Furthermore, compared with
      PSiNPs alone, PSiNPs coated with bovine serum albumin remarkably reduced
      nonspecific cellular uptake in vitro and prolonged blood circulation in vivo. 

PMID- 24138110
TI  - Growth in sense of self and sense of others predicts reduction in interpersonal
      problems in short-term dynamic but not in cognitive therapy.
AB  - OBJECTIVES: We investigated relationships between sense of self (SoS) and sense
      of others (SoO) and specific interpersonal problems in short-term dynamic and
      cognitive therapy. METHOD: 40 patients with Cluster C personality disorders from
      a RCT were included. The Achievement of Therapeutic Objective Scales (ATOS) was
      used to perform ratings of videotaped sessions. The Inventory of Interpersonal
      Problems Circumplex version was used as the outcome measure. RESULTS: There were
      significant relationships between growth in SoS and SoO and reductions of hostile
      dominant and hostile-submissive behaviors, as well as cold, social-avoidant and
      vindictive behaviors. Increase in SoO was also related to reductions in non
      assertive and domineering behaviors. However, the results were only present in
      the STDP treatment group.

PMID- 24138111
TI  - Surfing downhill: when should population range expansion be characterized by
      reductions in fitness?
AB  - Deleterious mutations are found in all populations. Their existence at low
      frequencies is easily understood, but explaining how they reach high frequencies
      has long been a challenging problem for population geneticists and evolutionary
      biologists. Some cases of apparently deleterious alleles are explained by
      pleiotropy or environmental context dependence, but for universally deleterious
      alleles, two mechanisms are generally invoked to explain how they can reach high
      frequencies: (i) genetic drift in small populations and (ii) 'hitchhiking' (sensu
      Maynard Smith J, Haigh J, Genetical Research, 1974, 23, 23-35) involving tight
      linkage to beneficial mutations. However, these oft-cited explanations do not
      immediately resolve the problem because many real populations of interest have
      population sizes and recombination rates that are large enough to render it
      nearly impossible for all but the most weakly deleterious (i.e. nearly neutral)
      mutations to establish and persist. Furthermore, both mechanisms are usually
      silent about patterns of intraspecific variation in mutation load. In this issue,
      Peischl S, Dupanloup I, Kirkpatrick M, Excoffier L (Molecular Ecology, 2013)
      develop and explore a mechanism that puts drift and hitchhiking of deleterious
      mutations into a specific spatial and demographic context: range expansions.
      Importantly, their findings provide a plausible explanation for puzzling
      empirical patterns, such as the paradoxical observation that genotypes at the
      leading edge of a range expansion are sometimes less fit than those in the
      ancestral range (when fitness is assessed in a common environment). 

PMID- 24138112
TI  - Synchrotron X-ray studies of rapidly evolving morphology of self-assembled
      nanoparticle films under lateral compression.
AB  - Interfacial nanostructures represent a class of systems that are highly relevant
      to studies of quasi-2D phases, chemical self-assembly, surfactant behavior, and
      biologically relevant membranes. Previous studies have shown that under lateral
      compression a Langmuir film of gold (Au) nanoparticles assembled at the liquid
      air interface exhibits rich mechanical behavior: it undergoes a rapid structural
      and morphological evolution from a monolayer to a trilayer via an intermediate
      hash-like phase. We report the results of studying this structural evolution
      using grazing incidence X-ray off-specular scattering (GIXOS). We utilize GIXOS
      to obtain a quantitative mapping of electron density profile normal to the liquid
      surface with a subnanometer resolution and follow the structural evolution of the
      Au nanoparticle film under lateral compression with a subminute temporal
      resolution. As the surface pressure is increased, the self-assembled nanoparticle
      monolayer first crinkles into a double-layer phase before forming a trilayer.
      This study reveals the existence of a transient bilayer phase and provides a
      microscopic picture of the particle-level crinkling phenomena of ultrathin films.
      These studies were previously impossible due to the relatively short time scales
      involved in crinkling formation of these transient phases and their intrinsically
      inhomogeneous nature. 

PMID- 24138113
TI  - An efficient ionic liquid mediated synthesis, cholinesterase inhibitory activity
      and molecular modeling study of novel piperidone embedded alpha,beta-unsaturated
      ketones.
AB  - A series of hitherto unreported piperidone embedded alpha,beta-unsaturated
      ketones were synthesized efficiently in ionic solvent and evaluated for
      cholinesterase inhibitory activities against acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) enzymes. Most of the synthesized compounds displayed
      good enzyme inhibition; therein compounds 7i and 7f displayed significant
      activity against AChE with IC50 values of 1.47 and 1.74 uM, respectively.
      Compound 6g showed the highest BChE inhibitory potency with IC50 value of 3.41
      uM, being 5 times more potent than galanthamine. Molecular modeling simulation
      was performed using AChE and BChE receptors extracted from crystal structure of
      human AChE and human BChE to determine the amino acid residues involved in the
      binding interaction of synthesized compounds and their relevant receptors. 

PMID- 24138114
TI  - Investigating characteristics of collaboration between nurse practitioners and
      medical practitioners in primary healthcare: a mixed methods multiple case study
      protocol.
AB  - AIM: To investigate characteristics of collaboration between nurse practitioners
      and medical practitioners in the primary healthcare setting in Australia.
      BACKGROUND: Recent definitions of collaboration in the literature describe it as
      being based on communication, shared decision-making and the respect and equality
      of team members. However, research demonstrates a tension between this
      theoretical ideal and how collaboration between nurse practitioners and medical
      practitioners occurs in practice. Different socialization processes of the two
      professions and legislative requirements influence collaborative practice. The
      way these two professions overcome traditional boundaries and realize
      collaborative practice in the primary healthcare setting needs to be examined.
      DESIGN: Mixed methods multiple case study including up to six sites with a
      minimum of six and a maximum of 20 participants in total. METHODS: Data on
      collaborative practice between nurse practitioners and medical practitioners in
      primary health care will be collected in three phases: (1) two-week direct
      observation in the practice setting to capture actual behaviour and context; (2)
      questionnaire to measure dimensions of collaboration; and (3) one-to-one semi
      structured interviews with nurse practitioners, medical practitioners and
      practice managers to record experiences, perceptions and understanding of
      collaboration. DISCUSSION: Triangulation of findings will generate a
      comprehensive understanding of how collaboration between nurse practitioners and
      medical practitioners in Australia occurs in the primary care setting. The
      results of this study will inform nurse practitioners, medical practitioners
      practice managers and policy makers on successful models of collaboration.

PMID- 24138115
TI  - Pronounced toxicity differences between homobifunctional protein cross-linkers
      and analogous monofunctional electrophiles.
AB  - Bifunctional electrophiles have been used in various chemopreventive,
      chemotherapeutic, and bioconjugate applications. Many of their effects in
      biological systems are traceable to their reactive properties, whereby they can
      modify nucleophilic sites in DNA, proteins, and other cellular molecules.
      Previously, we found that two different bifunctional electrophiles--diethyl
      acetylenedicarboxylate and divinyl sulfone--exhibited a strong enhancement of
      toxicity when compared with analogous monofunctional electrophiles in both human
      colorectal carcinoma cells and baker's yeast. Here, we have compared the
      toxicities for a broader panel of homobifunctional electrophiles bearing diverse
      electrophilic centers (e.g., isothiocyanate, isocyanate, epoxide, nitrogen
      mustard, and aldehyde groups) to their monofunctional analogues. Each
      bifunctional electrophile showed at least a 3-fold enhancement of toxicity over
      its monofunctional counterpart, although in most cases, the differences were even
      more pronounced. To explain their enhanced toxicity, we tested the ability of
      each bifunctional electrophile to cross-link recombinant yeast thioredoxin 2
      (Trx2), a known intracellular target of electrophiles. The bifunctional
      electrophiles were capable of cross-linking Trx2 to itself in vitro and to other
      proteins in cells exposed to toxic concentrations. Moreover, most cross-linkers
      were preferentially reactive with thiols in these experiments. Collectively, our
      results indicate that thiol-reactive protein cross-linkers in general are much
      more potent cytotoxins than analogous monofunctional electrophiles, irrespective
      of the electrophilic group studied.

PMID- 24138117
TI  - Oral administration of formalin killed Vibrio anguillarum cells improves growth
      and protection against challenge with Vibrio harveyi in banana shrimp.
AB  - Larval rearing in hatcheries and highly intensive grow-out culture practices
      followed in shrimp production systems favour the growth of potential pathogenic
      bacterial loads. This study reports the efficacy of formalin-killed vibrio
      bacterin on growth, survival and protection to challenge with virulent Vibrio
      harveyi and Vibrio anguillarum in juveniles of banana shrimp Fenneropenaeus
      merguiensis. Postlarvae 15 (0.24 +/- 0.01 g) were administered orally in
      different concentrations of bacterial preparation (0, 10(6) , 10(8) , 10(10) and
      10(12 ) CFU kg(-1) feed) for a period of 6 weeks. Physicochemical and microbial
      quality of water in larval rearing tanks, and growth and survival of the
      postlarvae were monitored at regular intervals, and body composition was
      estimated at the end of the experiment. Shrimps were challenged with V. harveyi
      and V. anguillarum, and cumulative mortality was calculated. The group receiving
      10(8)  CFU kg(-1) feed showed highest average weight gain (162.66 +/- 22.94 mg)
      and survival (90.33 +/- 4.5%) and lowest cumulative mortality following the
      challenge with V. anguillarum (26%) and V. harveyi (36.67%). The results of the
      study suggest that formalized vibrio administered orally to F. merguiensis
      postlarvae could induce both homologous and heterologous protection against V.
      anguillarum and V. harveyi. 'Vaccination' of shrimp postlarvae at hatcheries
      would help in preventing the losses due to vibriosis and the most susceptible
      stages of shrimp development. SIGNIFICANCE AND IMPACT OF THE STUDY: The study
      demonstrates the cross-protection offered by the oral feeding of formalin-killed
      Vibrio anguillarum against pathogenic V. harveyi challenge at the early
      developmental stages of banana shrimp, Fenneropenaeus merguiensis.

PMID- 24138116
TI  - Prediction and characterization of helper T-cell epitopes from pneumococcal
      surface adhesin A.
AB  - Pneumococcal surface adhesin A (PsaA) is a multifunctional lipoprotein known to
      bind nasopharyngeal epithelial cells, and is significantly involved in bacterial
      adherence and virulence. Identification of PsaA peptides that optimally bind
      human leucocyte antigen (HLA) and elicit a potent immune response would be of
      great importance to vaccine development. However, this is hindered by the
      multitude of HLA polymorphisms in humans. To identify the conserved
      immunodominant epitopes, we used an experimental dataset of 28 PsaA synthetic
      peptides and in silico methods to predict specific peptide-binding to HLA and
      murine MHC class II molecules. We also characterized spleen and cervical lymph
      node (CLN) -derived T helper (Th) lymphocyte cytokine responses to these peptides
      after Streptococcus pneumoniae strain EF3030 challenge in mice. Individual, yet
      overlapping, peptides 15 amino acids in length revealed residues of PsaA that
      consistently caused the highest interferon-gamma, interleukin-2 (IL-2), IL-5 and
      IL-17 responses and proliferation as well as moderate IL-10 and IL-4 responses by
      ex vivo re-stimulated splenic and CLN CD4+ T cells isolated from S. pneumoniae
      strain EF3030-challenged F1 (B6 * BALB/c) mice. In silico analysis revealed that
      peptides from PsaA may interact with a broad range of HLA-DP, -DQ and -DR
      alleles, due in part to regions lacking beta-turns and asparagine endopeptidase
      sites. These data suggest that Th cell peptides (7, 19, 20, 22, 23 and 24)
      screened for secondary structures and MHC class II peptide-binding affinities can
      elicit T helper cytokine and proliferative responses to PsaA peptides.

PMID- 24138118
TI  - Amino acid quantification in bulk soybeans by transmission Raman spectroscopy.
AB  - Soybeans are a commodity crop of significant economic and nutritional interest.
      As an important source of protein, buyers of soybeans are interested in not only
      the total protein content but also in the specific amino acids that comprise the
      total protein content. Raman spectroscopy has the chemical specificity to measure
      the twenty common amino acids as pure substances. An unsolved challenge, however,
      is to quantify varying levels of amino acids mixed together and bound in soybeans
      at relatively low concentrations. Here we report the use of transmission Raman
      spectroscopy as a secondary analytical approach to nondestructively measure
      specific amino acids in intact soybeans. With the employment of a transmission
      based Raman instrument, built specifically for nondestructive measurements from
      bulk soybeans, spectra were collected from twenty-four samples to develop a
      calibration model using a partial least-squares approach with a random-subset
      cross validation. The calibration model was validated on an independent set of
      twenty-five samples for oil, protein, and amino acid predictions. After Raman
      measurements, the samples were reduced to a fine powder and conventional wet
      chemistry methods were used for quantifying reference values of protein, oil, and
      18 amino acids. We found that the greater the concentrations (% by weight
      component of interest), the better the calibration model and prediction
      capabilities. Of the 18 amino acids analyzed, 13 had R(2) values greater than
      0.75 with a standard error of prediction c.a. 3-4% by weight. Serine, histidine,
      cystine, tryptophan, and methionine showed poor predictions (R(2) < 0.75), which
      were likely a result of the small sampling range and the low concentration of
      these components. It is clear from the correlation plots and root-mean-square
      error of prediction that Raman spectroscopy has sufficient chemical contrast to
      nondestructively quantify protein, oil, and specific amino acids in intact
      soybeans. 

PMID- 24138119
TI  - Interaction between hydroxyethyl starch and propofol: computational and
      laboratorial study.
AB  - BACKGROUND: Hydroxyethyl starch (HES) is one of the most used colloids for
      intravascular volume replacement during anesthesia. AIM: To investigate the
      existence of a chemical interaction between HES and the anesthetic propofol by in
      vitro propofol dosing, computational docking, and examination of a complex
      between propofol and HES by infrared (IR), ultraviolet (UV), and (1)H and (13)C
      nuclear magnetic resonance (NMR) spectroscopy. METHODS: Ten samples with human
      plasma mixed with HES or lactated Ringers (n = 5 for each fluid) were prepared,
      and the propofol free fraction was quantified until 50 min, using gas
      chromatography-mass spectrometry. The docking study was performed between HES and
      propofol and compared with controls. The binding affinities between HES and the
      small molecules were evaluated by binding free energy approximation (DeltaGb, kJ
      mol(-1)). The IR, UV, and NMR spectra were measured for propofol, HES, and a
      mixture of both obtained by the kneading method. RESULTS: Propofol concentrations
      were significantly lower in the HES samples than in the LR samples (p = .021).
      The spectroscopic characterization of propofol combined with HES revealed
      differences in spectra and docking studies reinforced a potential interaction
      between propofol and HES. CONCLUSIONS: Propofol and HES form a complex with
      different physical-bio-chemical behavior than the single drugs, which may be an
      important drug interaction. Further studies should evaluate its clinical effects.

PMID- 24138120
TI  - The relationship between vasomotor symptoms and menopause-associated dizziness.
AB  - CONCLUSION: Vasomotor symptoms (VMS) and especially hot flushes are negatively
      associated with recovery from menopause-related dizziness. A further study is
      justified to determine whether hormone replacement therapy (HRT) can shorten this
      recovery time. OBJECTIVES: This study aimed to compare the rate of recovery from
      dizziness between patients who had VMS and those who did not. We also evaluated
      the effect of HRT on recovery from dizziness. METHODS: The medical records of 85
      women aged between 40 and 59 years were analyzed retrospectively. The patients
      were asked detailed questions about their menopausal symptoms as well as any
      episodes of dizziness, which were diagnosed on the basis of neuro-otological
      examinations and were treated appropriately. All patients were followed up until
      dizziness improved. RESULTS: Over a 2-month period, the rate of recovery from
      vertigo was significantly higher in patients without VMS (no-VMS group, n = 38)
      than in those with VMS (VMS group, n = 29). In the VMS group, patients treated
      with HRT (n = 7) recovered from dizziness more quickly than those who were not
      treated with HRT (n = 22), although this difference was not statistically
      significant.

PMID- 24138121
TI  - Presence of keratin-specific antibody-forming cells in palatine tonsils of
      patients with pustulosis palmaris et plantaris (PPP) and its correlation with
      prognosis after tonsillectomy.
AB  - CONCLUSION: Keratin-specific immune responses in tonsils may be associated with
      the pathogenesis of pustulosis palmaris et plantaris (PPP). Evaluation of keratin
      specific immune responses in tonsils might be useful to predict the effectiveness
      of tonsillectomy for patients with PPP. OBJECTIVES: The aim of the present study
      was to clarify the role of keratin-specific immune responses in the pathogenesis
      of PPP in tonsils. It has been reported that anti-keratin antibodies in serum
      were higher in patients with PPP and decreased after tonsillectomy, indicating
      that anti-keratin antibodies might be generated in tonsils. METHODS: In order to
      demonstrate the presence of keratin-specific immune responses in tonsils, the
      numbers of keratin-specific antibody-forming cells (AFCs) in tonsillar and
      peripheral blood lymphocytes were examined by enzyme-linked immunospot assay. The
      prognosis of PPP was compared after tonsillectomy. RESULTS: The numbers of
      keratin-specific IgM and IgG AFCs in tonsils and of IgG AFCs in peripheral blood
      were significantly increased in patients with PPP. The numbers of keratin
      specific IgG AFCs in peripheral blood correlated positively with tonsil and serum
      IgG antibodies specific to keratin. Our data show that a good prognosis in
      patients with PPP depended on the numbers of keratin-specific IgG and IgM AFCs in
      peripheral blood and the levels of keratin-specific IgG antibodies in serum being
      significantly decreased 6 months after tonsillectomy.

PMID- 24138122
TI  - Reproductive versatility in legumes: the case of amphicarpy in Trifolium
      polymorphum.
AB  - Amphicarpy is a fascinating reproductive strategy, defined as fruit produced both
      below the soil surface and as aerial fruit on the same plant. Trifolium
      polymorphum is a grassland species subject to herbivory that combines amphicarpy
      with vegetative reproduction through stolons. Underground flowers have been
      described as obligate autogamous and aerial ones as self-compatible allogamous,
      with aerial floral traits favouring cross-pollination. In the present work we
      performed different pollination treatments on aerial flowers to analyse rates of
      pollen tube development and offspring fitness, measured as fruit set, seed
      production and germination percentage. This last variable was compared to that of
      seeds produced underground. No significant differences were found between fruit
      set in self- and cross-pollinations. Seed production was higher in self
      pollinations, which is consistent with the higher rate of pollen tube development
      observed in self-crosses. Spontaneous self-pollination is limited in aerial
      flowers; thus pollen transfer by means of a vector is required even within the
      same flower. Germination tests showed that aerial seeds produced after self- and
      cross-pollination did not differ in fitness, but underground seeds had higher
      germination percentage than aerial ones. Thus, we conclude that T. polymorphum
      has a mixed mating system. In grasslands with heavy grazing pressure, clonal
      propagation and underground seed production ensure persistence in the field. An
      intermediate level of selfing in aerial flowers ensures offspring, but
      morphological (herkogamy) and functional (dicogamy) floral traits maintain a
      window to incorporate genetic variability, allowing the species to tolerate
      temporal and spatial pressures.

PMID- 24138123
TI  - Pyridine-CF4: a molecule with a rotating cap.
AB  - The rotational spectrum of pyridine-CF4 has been investigated by molecular beam
      Fourier transform microwave spectroscopy in a supersonic expansion. The CF4
      moiety is located as a cap over the pyridine nitrogen, and the two parts are
      freely rotating with respect to each other. For this reason, in a first
      approximation, in the m = 0 state only the pyridine ring is rotating along the a
      axis, and the value of rotational constant A' is nearly the same of the constant
      A of isolated pyridine. The N...CCF4 distance is 3.372(1) A. The dissociation
      energy has been estimated, from the centrifugal distortion, to be ca. 10 kJ/mol. 

PMID- 24138124
TI  - Understanding the suicidal moment in adolescence.
AB  - Suicide attempts are more common in adolescence than in any other time in life,
      despite the low prevalence of actual suicide deaths among adolescents. Studies of
      adolescent suicide risk tend to focus on factors such as psychiatric diagnosis-
      particularly depression--and history of previous suicide attempts in predicting
      risk of future suicidal behavior. However, given that a large number of
      adolescent suicides are first-time attempts, understanding the circumstances that
      precede suicide attempts--including the nature of suicidal ideation and of the
      cognitive and emotional responses that precede ideation--is a critical part of
      preventing a potentially lethal attempt. We review the psychological precipitants
      that may inform how suicidal thoughts are transferred into action and examine the
      risk conferred by having a history of previous suicide attempts and ideation.

PMID- 24138125
TI  - Interactions of protamine with the marine bacterium, Pseudoalteromonas sp. NCIMB
      2021.
AB  - Pseudoalteromonas sp. NCIMB 2021 (NCIMB 2021) was grown in synthetic seawater
      (SSW) containing pyruvate, in the presence (SSW(++) ) and absence (SSW(-) ) of
      divalent cations. Cultures contained single cells. Addition of the cationic
      antibacterial peptide (CAP), protamine, did not inhibit, but rather increased,
      the growth of NCIMB 2021 in SSW(++) and caused the bacteria to grow in chains.
      Bacterial growth was assessed using turbidity, cell counts and the sodium salt of
      resazurin. In SSW(-) , NCIMB 2021 was no longer resistant to protamine. The
      minimum inhibitory concentration (MIC) was 5 mg ml(-1) . SIGNIFICANCE AND IMPACT
      OF THE STUDY: Protamine is a cationic antimicrobial peptide (CAP), which is
      active against a variety of bacteria. This is the first in-depth study of the
      interaction of protamine with a marine bacterium, Pseudoalteromonas sp. NCIMB
      2021. Our results show that protamine is only active in seawater in the absence
      of divalent cations. In the presence of the divalent cations, Mg(2+) and Ca(2+) ,
      protamine enhances the growth of Pseudoalteromonas sp. NCIMB 2021 and produces
      chains rather than individual cells. These are important considerations when
      deciding on applications for protamine and in terms of understanding its
      mechanism of action.

PMID- 24138126
TI  - Risk factors for oral diseases among workers with and without dental insurance in
      a national social security scheme in India.
AB  - OBJECTIVES: The target population for this cross sectional study comprises
      subjects with and without social security in a national social security scheme.
      The study aimed to compare and assess the risk factors for oral diseases among
      insured (organised sector) and non-insured workers (unorganised sector) in New
      Delhi, India. METHODS: The sample comprised a total of 2,752 subjects. Of these,
      960 workers belonged to the formal or organised sector with a social security and
      dental health insurance and 1,792 had no social security or dental insurance from
      the informal or unorganised sector. RESULTS: Significant differences were noted
      between the two groups for literacy levels, between-meal sugar consumption,
      tobacco-related habits and utilisation of dental care. Bleeding/calculus and
      periodontal pockets were present among 25% and 65.4% of insured workers,
      respectively. Similarly, 13.6% and 84.5% of non-insured workers had
      bleeding/calculus and periodontal pockets, respectively. The mean DMFT (decayed,
      missing, filled teeth) value among the insured workers and non-insured workers
      was 3.27 +/- 1.98 and 3.75 +/- 1.80, respectively. The association between
      absence of health insurance and dental caries was evident with an odds ratio (OR)
      of 1.94. Subjects with below graduate education were more prone to dental caries
      (OR = 1.62). Subjects who cleaned their teeth two or more times a day were less
      likely to have dental caries (OR = 1.47). Utilisation of dental care was
      inversely related to dental caries (OR = 1.25). CONCLUSION: The major risk
      factors for oral diseases in both the groups with similar socio-economic status
      were the lack of social security and health insurance, low literacy levels, high
      tobacco consumption and low levels of dental care utilisation.

PMID- 24138127
TI  - Sequential deoxyfluorination approach for the synthesis of protected
      alpha,beta,gamma-trifluoro-delta-amino acids.
AB  - Backbone-homologated amino acids have been synthesized, containing three vicinal
      fluorine atoms placed stereospecifically along the carbon chain. Different
      trifluoro stereoisomers are found to have contrasting conformations, consistent
      with known stereoelectronic effects associated with C-F bonds. 

PMID- 24138128
TI  - Does clenching reduce indirect head acceleration during rugby contact?
AB  - BACKGROUND: Concussions are common among athletes, with the potential to cause
      memory-related, physical, cognitive, emotional, and behavioral damage. A
      concussion is an acceleration/deceleration injury resulting from direct and
      indirect biomechanical forces transmitted to the cerebral tissues. From a sports
      dentistry viewpoint, increased mastication muscle activity or clenching due to
      the presence of a mouthguard may enhance cervical muscle activity, thereby
      reducing damage following impact. This relationship has not been previously
      investigated in the context of rugby. The purpose of this study was to
      investigate the effect of voluntary clenching on indirect head acceleration
      during attack- and defense-related drills. MATERIALS AND METHODS: A total of 12
      high school rugby players participated in the study. Linear acceleration of the
      head was measured using an accelerometer that took measurements in three axes.
      Masseter and sternocleidomastoid muscle activities were measured using wireless
      electromyography. These data were synchronized using digital video imaging
      software for analysis. The study protocol was approved by the Tokyo Dental
      College Ethics Committee. RESULTS AND CONCLUSIONS: Within the limitations of this
      study, the following results were obtained: the activities performed during rugby
      practice involved relatively small indirect head acceleration and masseter and
      sternocleidomastoid muscle activities. After the young male rugby players were
      instructed to clench their masseter muscles, a marked decrease in head
      acceleration was observed.

PMID- 24138129
TI  - Surveillance of ischemic heart disease should include physician billing claims:
      population-based evidence from administrative health data across seven Canadian
      provinces.
AB  - BACKGROUND: Canadian provinces and territories routinely collect health
      information for administrative purposes. This study used Canadian medical and
      hospital administrative data for population-based surveillance of diagnosed
      ischemic heart disease (IHD). METHODS: Hospital discharge abstracts and physician
      billing claims data from seven provinces were analyzed to estimate prevalence and
      incidence of IHD using three validated algorithms: a) one hospital discharge
      abstract with an IHD diagnosis or procedure code (1H); b) 1H or at least three
      physician claims within a one-year period (1H3P) and c) 1H or at least two
      physician claims within a one-year period (1H2P). Crude and age-standardized
      prevalence and incidence rates were calculated for Canadian adults aged 20 +.
      RESULTS: IHD prevalence and incidence varied by province, were consistently
      higher among males than females, and increased with age. Prevalence and incidence
      were lower using the 1H method compared to using the 1H2P or 1H3P methods in all
      provinces studied for all age groups. For instance, in 2006/07, crude prevalence
      by province ranged from 3.4%-5.5% (1H), from 4.9%-7.7% (1H3P) and from 6.0%-9.2%
      (1H2P). Similarly, crude incidence by province ranged from 3.7-5.9 per 1,000
      (1H), from 5.0-6.9 per 1,000 (1H3P) and from 6.1-7.9 per 1,000 (1H2P).
      CONCLUSIONS: Study findings show that incidence and prevalence of diagnosed IHD
      will be underestimated by as much as 50% using inpatient data alone. The addition
      of physician claims data are needed to better assess the burden of IHD in Canada.

PMID- 24138130
TI  - Standardization of skin cleansing in vivo: part I. Development of an Automated
      Cleansing Device (ACiD).
AB  - BACKGROUND: To date, there are no legally binding requirements concerning product
      testing in cosmetics. This leads to various manufacturer-specific test methods
      and absent transparent information on skin cleansing products. A standardized in
      vivo test procedure for assessment of cleansing efficacy and corresponding
      barrier impairment by the cleaning process is needed, especially in the
      occupational context where repeated hand washing procedures may be performed at
      short intervals. METHODS: For the standardization of the cleansing procedure, an
      Automated Cleansing Device (ACiD) was designed and evaluated. Different smooth
      washing surfaces of the equipment for ACiD (incl. goat hair, felt, felt covered
      with nitrile caps) were evaluated regarding their skin compatibility. RESULTS:
      ACiD allows an automated, fully standardized skin washing procedure. Felt covered
      with nitrile as washing surface of the rotating washing units leads to a
      homogenous cleansing result and does not cause detectable skin irritation,
      neither clinically nor as assessed by skin bioengineering methods (transepidermal
      water loss, chromametry). CONCLUSIONS: Automated Cleansing Device may be useful
      for standardized evaluation of the cleansing effectiveness and parallel
      assessment of the corresponding irritancy potential of industrial skin cleansers.
      This will allow objectifying efficacy and safety of industrial skin cleansers,
      thus enabling market transparency and facilitating rational choice of products.

PMID- 24138131
TI  - Long-term increase in serum cholesterol levels in ulcerative colitis patients
      treated with cyclosporine: an underdiagnosed side effect frequently associated
      with other drug-related complications.
AB  - INTRODUCTION: Several serious side effects may limit the use of cyclosporine.
      Cyclosporine has been reported to increase the total cholesterol level; however,
      the change in serum cholesterol levels before and after cyclosporine therapy has
      not been examined in ulcerative colitis (UC) patients. The purpose of this
      article was to compare serum cholesterol levels before and after cyclosporine
      therapy in patients with refractory UC and to examine the relationship between
      serum cholesterol levels and other common side effects. PATIENTS AND METHODS: We
      prospectively assessed serum cholesterol levels in UC patients who had been
      treated with cyclosporine. Data of 72 patients were analyzed and compared to a
      control group treated with Infliximab. RESULTS: The average duration of
      cyclosporine therapy was 9.6 months, and side effects developed in 52 patients.
      Elevated cholesterol levels were detected in 47.2% of the patients. Serum
      cholesterol levels were significantly increased during and after discontinuation
      of cyclosporine therapy compared to the time before use of the drug. However,
      cholesterol levels measured during cyclosporine therapy were significantly higher
      compared to the time after its discontinuation (p < 0.001). Patients with drug
      related side effects showed higher cholesterol levels after discontinuation of
      the therapy compared to those who did not experience any adverse events.
      CONCLUSIONS: Our findings suggest that cyclosporine therapy may result in
      increased serum cholesterol levels even in the long-term, after discontinuation
      of the therapy. Considering that significantly higher post-therapy cholesterol
      levels were more common in patients who developed drug-related complications,
      routine measurement of serum cholesterol may increase the safety of the drug.

PMID- 24138132
TI  - The case for nurses as central providers of health and social care services for
      ex-offenders: a discussion paper.
AB  - AIMS: A discussion on the case for nurse-led community delivery of health and
      social care interventions to ex-offenders. BACKGROUND: Ex-offenders re-enter
      their communities with limited pre-release preparation for the continuity of
      access to health care once outside prison. Once released, these individuals
      become hard to reach, do not consider health a priority and consequently use
      services to address their health and social care needs in a crisis-led way.
      Nevertheless, how nurses can best support these health-excluded group of
      individuals in the community remains vague and requires discussion. DESIGN:
      Discussion paper. DATA SOURCES: Several databases were searched for papers
      published in English from 1990-2012 using the Population, Intervention and
      Outcome framework to help structure search. DISCUSSION: It is argued that current
      dominant discourses around equity of care are contradicted in the provision of
      health and social care services to ex-offenders in the community. Effective
      engagement with community interventions may be achieved if ex-offenders maintain
      contact with frontline providers who can support both their structural and health
      needs. IMPLICATION FOR NURSING: Nurses are uniquely positioned to initiate and
      sustain contact with ex-offenders, intervening at points of greatest need in the
      community to address the socially significant health and social care issues that
      plague them. CONCLUSION: The use of nurses in the provision of health and social
      care interventions to ex-offenders is a strategy, which could increase equity in
      access to health care, reduce reoffending and improve both the health and life
      chances of these individuals.

PMID- 24138133
TI  - The importance of an evolutionary perspective in conservation policy planning.
AB  - Prioritization of taxa for conservation must rest on a foundation of correctly
      identified species boundaries, enhanced by an understanding of evolutionary
      history and phylogenetic relationships. Therefore, we can incorporate both
      evolutionary and ecological processes into efforts to sustain biodiversity. In
      this issue of Molecular Ecology, Malaney & Cook (2013) highlight the critical
      value of an evolutionary biogeographical approach, combining multilocus
      phylogeography with climatic niche modelling to infer phylogenetically weighted
      conservation priorities for evolutionary lineages of jumping mice across North
      America. Remarkably, they find that the Preble's meadow jumping mouse (Zapus
      hudsonius preblei), long debated as a threatened taxon, in fact represents the
      southern terminus of a relatively uniform lineage that expanded well into Alaska
      during the Holocene. By contrast, some other relictual and phylogenetically
      divergent taxa of jumping mice likely warrant greater conservation priority. This
      study highlights the value of integrative approaches that place current taxonomy
      in a broader evolutionary context to identify taxa for conservation assessment,
      but also highlights the challenges in maintaining potential for adaptive
      responses to environmental change.

PMID- 24138134
TI  - Polar and magnetic layered A-site and rock salt B-site-ordered NaLnFeWO6 (Ln =
      La, Nd) perovskites.
AB  - We have expanded the double perovskite family of materials with the unusual
      combination of layered order in the A sublattice and rock salt order over the B
      sublattice to compounds NaLaFeWO6 and NaNdFeWO6. The materials have been
      synthesized and studied by powder X-ray diffraction, neutron diffraction,
      electron diffraction, magnetic measurements, X-ray absorption spectroscopy,
      dielectric measurements, and second harmonic generation. At room temperature, the
      crystal structures of both compounds can be defined in the noncentrosymmetric
      monoclinic P2(1) space group resulting from the combination of ordering both in
      the A and B sublattices, the distortion of the cell due to tilting of the
      octahedra, and the displacement of certain cations. The magnetic studies show
      that both compounds are ordered antiferromagnetically below T(N) ~ 25 K for
      NaLaFeWO6 and at ~21 K for NaNdFeWO6. The magnetic structure of NaNdFeWO6 has
      been solved with a propagation vector k = ((1/2) 0 (1/2)) as an antiferromagnetic
      arrangement of Fe and Nd moments. Although the samples are potential
      multiferroics, the dielectric measurements do not show a ferroelectric response.

PMID- 24138135
TI  - Children's norm enforcement in their interactions with peers.
AB  - This study investigates how children negotiate social norms with peers. In Study
      1, 48 pairs of 3- and 5-year-olds (N = 96) and in Study 2, 48 pairs of 5- and 7
      year-olds (N = 96) were presented with sorting tasks with conflicting
      instructions (one child by color, the other by shape) or identical instructions.
      Three-year-olds differed from older children: They were less selective for the
      contexts in which they enforced norms, and they (as well as the older children to
      a lesser extent) used grammatical constructions objectifying the norms ("It works
      like this" rather than "You must do it like this"). These results suggested that
      children's understanding of social norms becomes more flexible during the
      preschool years.

PMID- 24138136
TI  - Direct probing of the free-energy penalty for helix reversals and chiral
      mismatches in chiral supramolecular polymers.
AB  - The amplification of chirality, where a small imbalance in a chiral constituent
      is propagated into a strong optical purity, can occur in the spontaneous
      formation of helical 1-D stacks of molecules stabilized by hydrogen bonding, also
      known as supramolecular polymers. We have extended a statistical model by van
      Gestel et al. describing the highly nonlinear relationship between supramolecular
      helicity and enantiomeric excess for mixtures of enantiomers (the majority-rules
      effect) and quantitatively account for how this affects the thermodynamic
      stability of the assemblies. Our method allows for a direct comparison with
      experimental data, providing an unambiguous determination of the key parameters
      of the model (i.e., the mismatch and the helix reversal penalties). We
      demonstrate the successful application of this model to calorimetry data for bis
      urea-based helical nanotubes, showing that reversals in the handedness of these
      nanotubes are not all that rare even though the helix reversal penalty is fairly
      large. By contrast, the mismatch penalty we obtain is small, implying that a
      large proportion of enantiomers are present in tube fractions not of their
      preferred handedness. 

PMID- 24138137
TI  - Simultaneous detection of six urinary pteridines and creatinine by high
      performance liquid chromatography-tandem mass spectrometry for clinical breast
      cancer detection.
AB  - Recent preliminary studies have implicated urinary pteridines as candidate
      biomarkers in a growing number of malignancies including breast cancer. While the
      developments of capillary electrophoresis-laser induced fluorescence (CE-LIF),
      high performance liquid chromatography (HPLC), and liquid chromatography-mass
      spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable
      these findings, limitations including poor pteridine specificity, asynchronous or
      nonexistent renal dilution normalization, and a lack of information regarding
      adduct formation in mass spectrometry techniques utilizing electrospray
      ionization (ESI) have prevented application of these techniques to a larger
      clinical setting. In this study, a simple, rapid, specific, and sensitive high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method
      has been developed and optimized for simultaneous detection of six pteridines
      previously implicated in breast cancer and creatinine as a renal dilution factor
      in urine. In addition, this study reports cationic adduct formation of urinary
      pteridines under ESI-positive ionization for the first time. This newly developed
      technique separates and detects the following six urinary pteridines: 6
      biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and
      xanthopterin, as well as creatinine. The method detection limit for the
      pteridines is between 0.025 and 0.5 MUg/L, and for creatinine, it is 0.15 MUg/L.
      The method was also validated by spiked recoveries (81-105%), reproducibility
      (RSD: 1-6%), and application to 25 real urine samples from breast cancer positive
      and negative samples through a double-blind study. The proposed technique was
      finally compared directly with a previously reported CE-LIF technique, concluding
      that additional or alternative renal dilution factors are needed for proper
      investigation of urinary pteridines as breast cancer biomarkers. 

PMID- 24138138
TI  - Airway hyperresponsiveness is associated with airway remodeling but not
      inflammation in aging Cav1-/- mice.
AB  - BACKGROUND: Airway inflammation and airway remodeling are the key contributors to
      airway hyperresponsiveness (AHR), a characteristic feature of asthma. Both
      processes are regulated by Transforming Growth Factor (TGF)-beta. Caveolin 1
      (Cav1) is a membrane bound protein that binds to a variety of receptor and
      signaling proteins, including the TGF-beta receptors. We hypothesized that
      caveolin-1 deficiency promotes structural alterations of the airways that develop
      with age will predispose to an increased response to allergen challenge. METHODS:
      AHR was measured in Cav1-deficient and wild-type (WT) mice 1 to 12 months of age
      to examine the role of Cav1 in AHR and the relative contribution of inflammation
      and airway remodeling. AHR was then measured in Cav1-/- and WT mice after an
      ovalbumin-allergen challenge performed at either 2 months of age, when remodeling
      in Cav1-/- and WT mice was equivalent, and at 6 months of age, when the Cav1-/-
      mice had established airway remodeling. RESULTS: Cav1-/- mice developed increased
      thickness of the subepithelial layer and a correspondingly increased AHR as they
      aged. In addition, allergen-challenged Cav1-/- mice had an increase in AHR
      greater than WT mice that was largely independent of inflammation. Cav1-/- mice
      challenged at 6 months of age have decreased AHR compared to those challenged at
      2 months with correspondingly decreased BAL IL-4 and IL-5 levels, inflammatory
      cell counts and percentage of eosinophils. In addition, in response to OVA
      challenge, the number of goblet cells and alpha-SMA positive cells in the airways
      were reduced with age in response to OVA challenge in contrast to an increased
      collagen deposition further enhanced in absence of Cav1. CONCLUSION: A lack of
      Cav1 contributed to the thickness of the subepithelial layer in mice as they aged
      resulting in an increase in AHR independent of inflammation, demonstrating the
      important contribution of airway structural changes to AHR. In addition, age in
      the Cav1-/- mice is a contributing factor to airway remodeling in the response to
      allergen challenge.

PMID- 24138139
TI  - Human protamine-1 as an MRI reporter gene based on chemical exchange.
AB  - Genetically engineered reporters have revolutionized the understanding of many
      biological processes. MRI-based reporter genes can dramatically improve our
      ability to monitor dynamic gene expression and allow coregistration of
      subcellular genetic information with high-resolution anatomical images. We have
      developed a biocompatible MRI reporter gene based on a human gene, the human
      protamine-1 (hPRM1). The arginine-rich hPRM1 (47% arginine residues) generates
      high MRI contrast based on the chemical exchange saturation transfer (CEST)
      contrast mechanism. The 51 amino acid-long hPRM1 protein was fully synthesized
      using microwave-assisted technology, and the CEST characteristics of this protein
      were compared to other CEST-based contrast agents. Both bacterial and human cells
      were engineered to express an optimized hPRM1 gene and showed higher CEST
      contrast compared to controls. Live cells expressing the hPRM1 reporter gene, and
      embedded in three-dimensional culture, also generated higher CEST contrast
      compared to wild-type live cells. 

PMID- 24138141
TI  - Tissue-specific IL-10 secretion profile from term human fetal membranes
      stimulated with pathogenic microorganisms associated with preterm labor in a two
      compartment tissue culture system.
AB  - OBJECTIVE: Interleukin (IL)-10 is a cytokine with anti-inflammatory properties
      that plays pivotal roles in immune recognition and maintenance of pregnancy,
      limiting the harmful effects of pro-inflammatory modulators. The aim of this work
      was to characterize the contribution of amnion and choriodecidua regions of the
      human fetal membranes in the production of IL-10 after selective stimulation with
      Candida albicans, Gardnerella vaginalis and Streptococcus agalactiae. METHODS:
      Pre-labor human fetal membranes were cultured in a two-compartment tissue culture
      system and stimulated with 1 * 10(6) CFU/ml of each pathogen added to either the
      amniotic or choriodecidual region or both. RESULTS: Candida albicans and G.
      vaginalis were the pathogens most effective in inducing IL-10 secretion,
      increasing 20 and 10 times, respectively, the levels of this cytokine in the
      choriodecidual compartment. Stimulation with S. agalactiae was effective only in
      the choriodecidual region, increasing two times IL-10 concentration. CONCLUSIONS:
      Synthesis and secretion of IL-10 in response to three different pathogens
      associated with intrauterine infection and preterm birth are differential and
      depend on the nature of the microorganism and initial contact region.

PMID- 24138142
TI  - Endovascular correction of an infantile intracranial venous outflow obstruction.
AB  - The authors report on the case of a 7-year-old boy who presented with a reduced
      level of activity, macrocephaly, prominent scalp veins, and decreased left-sided
      visual acuity. Imaging workup demonstrated generalized cerebral volume loss,
      bilateral chronic subdural hematomas, absent left sigmoid sinus, hypoplastic left
      transverse sinus, and severe focal weblike stenosis of the right sigmoid sinus.
      Right sigmoid sinus angioplasty and stent insertion was performed, with an
      immediate reduction in the transduced intracranial venous pressure gradient
      across the stenosis (from 22 to 3 mm Hg). Postprocedural diminution of prominent
      scalp and forehead veins and spinal venous collateral vessels was followed by a
      progressive improvement in visual acuity and physical activity over a 1-year
      follow-up period, supporting the efficacy of angioplasty and stent insertion in
      intracranial venous outflow obstruction. There are multiple potential causes of
      intracranial venous hypertension in children. Development of dural sinus stenosis
      in infancy may be one such cause, mimicking the clinical presentation of other
      causes such as vein of Galen malformations. This condition can be ameliorated by
      early endovascular revascularization. 

PMID- 24138143
TI  - Impact of posterior cerebral artery involvement on long-term clinical and social
      outcome of pediatric moyamoya disease.
AB  - OBJECT: In the study of pediatric moyamoya disease, information on long-term
      social outcomes and risk factors for unfavorable social outcomes remains
      insufficient. The authors analyzed the long-term results of surgical
      revascularization for pediatric patients with moyamoya disease to determine
      whether the involvement of a stenoocclusive lesion in the posterior cerebral
      artery (PCA), relatively common in pediatric moyamoya disease, represents an
      underlying predictor for unfavorable social outcomes. METHODS: Prospectively
      collected data on 61 consecutive patients with moyamoya disease who had undergone
      combined bypass surgery were analyzed. Neuroradiological features and other
      baseline clinical factors were incorporated into univariate and multivariate
      analyses to determine any association with an unfavorable social outcome, defined
      as difficulty attending regular school or obtaining regular employment. RESULTS:
      Posterior cerebral artery involvement detected by angiography on admission was
      noted in 22 (36.1%) of the 61 patients. Follow-up data were acquired in 56
      patients (91.8%), and the mean follow-up period was 15.8 years. While transient
      ischemic attacks were eliminated in 52 (92.9%) of these 56 patients after
      surgery, and late-onset ischemic stroke was observed in only 1 patient during the
      follow-up period, 10 (17.9%) experienced an unfavorable social outcome. Although
      younger age at onset, longer duration between onset and surgery, infarction
      present on preoperative neuroradiological images, and PCA involvement had been
      identified as risk factors for an unfavorable social outcome in univariate
      analysis, only infarction present on preoperative images and PCA involvement
      remained statistically significant after multivariate adjustment. CONCLUSIONS:
      Posterior cerebral artery involvement can be considered one of the underlying
      risk factors for unfavorable social outcome and should be studied further to
      improve social outcome in pediatric moyamoya disease.

PMID- 24138144
TI  - Recurrent and self-remitting sixth cranial nerve palsy: pathophysiological
      insight from skull base chondrosarcoma.
AB  - Palsy of the abducens nerve is a neurological sign that has a wide range of
      causes due to the nerve's extreme vulnerability. Need of immediate neuroimaging
      is a matter of debate in the literature, despite the risks of delaying the
      diagnosis of a skull base tumor. The authors present 2 cases of skull base tumors
      in which the patients presented with recurrent and self-remitting episodes of
      sixth cranial nerve palsy (SCNP). In both cases the clinical history exceeded 1
      year. In a 17-year-old boy the diagnosis was made because of the onset of
      headache when the tumor reached a very large size. In a 12-year-old boy the tumor
      was incidentally diagnosed when it was still small. In both patients surgery was
      performed and the postoperative course was uneventful. Pathological diagnosis of
      the tumor was consistent with that of a chondrosarcoma in both cases. Recurrent
      self-remitting episodes of SCNP, resembling transitory ischemic attacks, may be
      the presenting sign of a skull base tumor due to the anatomical relationships of
      these lesions with the petroclival segment of the sixth cranial nerve. Physicians
      should promptly recommend neuroimaging studies if SCNP presents with this
      peculiar course. 

PMID- 24138145
TI  - The role of surgery in optic pathway/hypothalamic gliomas in children.
AB  - OBJECT: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign tumors
      situated in an exquisitely sensitive brain region. The location and natural
      history of OPHGs has led to much debate about optimal treatment. This paper
      revisits the role of and optimal timing of debulking surgery in OPHG. METHODS:
      This paper presents a series of cases managed by the neuro-oncology team at Alder
      Hey Children's Hospital and a single surgeon. Data were collected retrospectively
      for periods prior to 2009 and prospectively thereafter. Tailored treatment
      strategies were used, including observation and combinations of surgery,
      chemotherapy, and radiotherapy. Tumor control rates and outcomes are reviewed.
      RESULTS: Forty-two patients were treated between 1998 and 2011. Their median age
      at diagnosis was 5 years 7 months. Nineteen patients were positive for
      neurofibromatosis Type 1 (NF1) and 23 patients were negative for NF1. The median
      duration of follow-up was 77 months (range 21.8-142.3 months). Presenting
      symptoms included visual impairment (in 50% of cases), headache (in 24%), and
      hypothalamic/pituitary dysfunction (in 29%). Twenty-two debulking procedures were
      performed in 21 patients. Four biopsies (3 open, 1 endoscopic) were also
      performed. The histological diagnosis was pilocytic astrocytoma in 21 patients
      and pilomyxoid astrocytoma in 2 patients. Ten patients (Group 1) had primary
      surgical debulking alone and were then observed. Four patients (Group 2) had
      surgical debulking, plus planned chemotherapy within 3 months. Seven patients
      (Group 3) required surgical debulking for progressive disease following a variety
      of treatments. Patient age had the greatest impact on subsequent tumor
      progression. In total, 13 patients received chemotherapy, 4 on initial
      presentation, 4 in combination with surgery, and 5 for further tumor progression.
      Five patients were treated with radiotherapy, 3 prior to referral to Alder Hey.
      Eleven patients required shunt insertion for hydrocephalus. Vision was stabilized
      for 74% of patients. The number of patients with hypothalamic/pituitary
      dysfunction increased from 12 at presentation to 16 by the end of treatment. The
      overall survival rate was 93%. Three patients died-1 from tumor progression, 1
      from infective complications from tumor biopsy, and 1 from a spontaneous
      posterior fossa hemorrhage. NF1 was associated with improved outcome-fewer
      patients required active intervention and rates of visual impairment and/or or
      hypothalamic/pituitary dysfunction were lower. CONCLUSIONS: Good long-term
      survival and functional outcomes can be achieved in children with OPHG. Tumor
      control was achieved through an individualized approach using surgery,
      chemotherapy, or radiotherapy in varied combinations. The authors aim to limit
      radiotherapy to cases involving older children in whom other therapies have
      failed, due to the well-described and often devastating late effects associated
      with midline cranial irradiation. Surgery has a clear role for diagnosis, tumor
      control, and relief of mass effect. In particular, primary surgical debulking of
      tumor (without adjuvant therapy) is safe and effective. Recent advances in
      intraoperative MRI may add value and need further assessment.

PMID- 24138146
TI  - Dependency of seed dormancy types on embryo traits and environmental conditions
      in Ribes species.
AB  - The hypothesis that seed dormancy may be dependent on environmental conditions
      and seed morphological traits was tested for six Ribes species, across an
      altitudinal gradient of 1300 m and a longitudinal separation of 120 degrees .
      Embryo measurements and seed germination experiments were conducted for R.
      alpinum L., R. hudsonianum Richardson var. petiolare (Douglas) Jancz., R.
      nevadaense Kellogg, R. roezlii Regel var. cruentum (Greene) Rehder and R.
      speciosum Pursh, and data taken from the literature for R. multiflorum Kit. ex
      Schult. ssp. sandalioticum Arrigoni. Germination was compared with seed viability
      to reveal proportional seed dormancy, which was then correlated to seed/embryo
      morphological traits and these traits related to the seed provenance environment.
      The embryos of all the investigated species are linear underdeveloped and all had
      a morphological component of seed dormancy (MD). Seeds of R. roezlii, R.
      hudsonianum and R. nevadaense required a temperature and/or hormone pre-treatment
      in order to germinate, highlighting morphophysiological seed dormancy (MPD). Seed
      dormancy was found to be strongly negatively correlated with embryo length, but
      not with embryo to seed (E:S) ratio or seed mass. Initial embryo length was
      positively related to mean annual temperature. Seed dormancy in the investigated
      Ribes species could be quantified and predicted by the interaction of embryo
      traits and environmental conditions. This approach may be helpful in assessing
      and predicting seed dormancy in the Ribes genus and in other genera and families
      with underdeveloped embryos. 

PMID- 24138147
TI  - A new transplant program in China: Health officials hope to phase out use of
      executed prisoner's organs.

PMID- 24138150
TI  - Dialysis-associated steal syndrome.

PMID- 24138151
TI  - The anatomy of the caudal zona incerta in rodents and primates.
AB  - The caudal zona incerta is the target of a recent modification of established
      procedures for deep brain stimulation (DBS) for Parkinson's disease and tremor.
      The caudal zona incerta contains a number of neuronal populations that are
      distinct in terms of their cytoarchitecture, connections, and pattern of
      immunomarkers and is located at a position where a number of major tracts
      converge before turning toward their final destination in the forebrain. However,
      it is not clear which of the anatomical features of the region are related to its
      value as a target for DBS. This paper has tried to identify features that
      distinguish the caudal zona incerta of rodents (mouse and rat) and primates
      (marmoset, rhesus monkey, and human) from the remainder of the zona incerta. We
      studied cytoarchitecture, anatomical relationships, the pattern of immunomarkers,
      and gene expression in both of these areas. We found that the caudal zona incerta
      has a number of histological and gene expression characteristics that distinguish
      it from the other subdivisions of the zona incerta. Of particular note are the
      sparse population of GABA neurons and the small but distinctive population of
      calbindin neurons. We hope that a clearer appreciation of the anatomy of the
      region will in the end assist the interpretation of cases in which DBS is used in
      human patients. 

PMID- 24138153
TI  - Conversion disorder and mass psychogenic illness in child neurology.
AB  - A common problem faced by neurologists is the existence of disorders that present
      with neurological symptoms but do not have identifiable neurological bases.
      Conversion disorder is the most common of these disorders. In some situations,
      members of a cohesive social group will develop the same or similar symptoms.
      This review discusses conversion disorder in children, with an emphasis on
      function movement disorders. It also reviews a recent occurrence of mass
      psychogenic illness in New York State with discussion of the key features of mass
      psychogenic illness. 

PMID- 24138152
TI  - Interprofessional team dynamics and information flow management in emergency
      departments.
AB  - AIM: In Emergency Departments, fragmentation and breakdown in information
      exchange can be important factors leading to adverse events. This article aims to
      consider the critical aspects of collaborative teamwork in Emergency Departments
      that may have an impact on the information flow. BACKGROUND: On the basis of
      Distributed Cognition Theory, we have assumed that cognitive outcomes in critical
      care settings are not confined to the thoughts of isolated individuals; rather,
      they are better understood as properties of a distributed cognitive system across
      the minds of the clinical team members and across the technological artefacts.
      DESIGN: We report on an exploratory ethnographic study of two Emergency
      Departments. METHODS: Data were collected over a period of four months in 2008
      via observation and interviews. RESULTS: The results highlight a specific
      distribution of cognitive work between physicians and nurses. The nurse's roles
      as information highlighter, memory keeper and process organizer helped to ensure
      the information flow and to overcome some of the problems identified with the
      computer-assisted communication process. Such distribution of cognitive work
      improved care quality, but it crossed established professional boundaries.
      CONCLUSION: As cross-boundary distribution of cognitive work in Emergency
      Departments can be perceived as role substitution, building an interprofessional
      working system is needed to avoid information breakdown in fast-moving contexts.
      To realize an interprofessional working system, practice-based training is
      required, aimed at developing a deep understanding of team cognition.

PMID- 24138154
TI  - Effects of rotigotine on Parkinson's disease-related sleep disturbances.
AB  - INTRODUCTION: Sleep abnormalities are a frequent non-motor symptom and a
      prominent cause of disability in patients with Parkinson's disease (PD). AREAS
      COVERED: This review discusses what is currently known about the characteristics
      of sleep disturbances in PD patients and attempts to clarify the role of
      dopaminergic pathways in their pathogenesis as well as the beneficial effect of
      dopaminergic agents in their treatment. In particular, this review will focus on
      the effects of transdermal rotigotine on improving PD-related sleep disorders.
      EXPERT OPINION: Sleep disturbances are common in PD, and these disturbances can
      be reduced or resolved, in large part, by preventing or attenuating nocturnal and
      early morning motor and non-motor symptoms of PD. The studies discussed within
      this review suggest that sleep disorders are not just a consequence of motor
      impairment and dopaminergic therapy but are an integral part of the
      neurodegenerative process of PD. This is supported by the appearance of specific
      sleep disturbances, which are related to degeneration of the brainstem areas
      involved in the regulation of sleep/wake states in advance of typical PD
      symptoms. Development of more detailed diagnostic tools aimed at detecting sleep
      disturbances and at defining the main causative factors of sleep disturbances in
      PD will lead to improved treatment of these disturbances.

PMID- 24138156
TI  - Calculated dipole moments for silicon and phosphorus compounds of astrophysical
      interest.
AB  - Dipole moments, which contribute to the intensities of rotational transitions and
      also affect reactivity, have been computed for nearly 80 compounds with up to 6
      atoms containing silicon or phosphorus. More than a dozen of the set have been
      detected in interstellar or circumstellar media. The remaining ones are related
      to these, and several of them may be found in space in the future. We compare
      results from the commonly used B3LYP level of density functional theory with ab
      initio results at the coupled cluster CCSD(T)/RCCSD(T) levels of theory.
      Correlation consistent basis sets as large as quintuple zeta quality were used,
      and extrapolations to the estimated complete basis set (CBSE) limit were
      performed for almost all of the species with coupled cluster theory. In addition
      to evaluating the accuracy of the results against available data, we explore
      various issues: the critical importance of including diffuse basis functions, the
      range of basis set dependence exhibited by the suite of molecules, and the
      presence of low-lying excited states for some species. Dipole polarizabilities
      are also reported at the CCSD(T)/RCCSD(T) CBSE level. 

PMID- 24138155
TI  - Peripartal calcium homoeostasis of multiparous dairy cows fed rumen-protected
      rice bran or a lowered dietary cation/anion balance diet before calving.
AB  - Milk fever is one of the most important metabolic diseases in dairy cattle.
      Reducing the dietary cation/anion balance (DCAD) with anionic salts is a common
      prevention strategy. However, many small European farms cannot use total mixed
      rations (TMR) in the close-up period. Including anionic salts in compound feeds
      can result in feed refusals and moderate inclusions to preserve feed palatability
      results in insufficient DCAD reduction. Rumen-protected rice bran induces the
      adaptation of Ca metabolism in dairy cows by a reduction of Ca intake and by a
      reduction of the availability of dietary Ca. In the presence of a negative
      control, rumen-protected rice bran (2.8 kg/day) was compared with a lowered DCAD
      diet (from 269 to 4 meq/kg DM) in their effect to prevent milk fever. In a
      randomized block design, 45 multiparous Holstein cows joined the trial
      sequentially from 21 days before the expected calving date and were observed
      until the 8th week of lactation. Feed and nutrient intakes were recorded, and Ca,
      P, Mg in serum and urine, urine pH, serum NEFA and milk production in early
      lactation were compared. Feeding rumen-protected rice bran before calving
      improved the recovery of calcaemia after calving and had a positive effect on DMI
      after calving. The moderately low DCAD diet did not positively influence serum Ca
      at calving. Calcaemia recovered even later than in control, and cows showed
      reduced DMI post-calving and higher NEFA levels in the first 36 h after calving.
      This moderate reduction of DCAD did not provide an intermediate prevention level
      indicating that DCAD needs to be reduced to the recommended levels to prevent
      milk fever. Rumen-protected rice bran may be a suitable feed to reduce
      hypocalcaemia post-partum and can be included in pre-calving compound feeds
      representing a palatable alternative to anionic salts. 

PMID- 24138157
TI  - Molecular field analysis of trophic relationships in soil-dwelling invertebrates
      to identify mercury, lead and cadmium transmission through forest ecosystems.
AB  - Contamination pathways in complex food chains in soil ecosystems can be difficult
      to elucidate. Molecular analysis of predator gut content can, however, rapidly
      reveal previously unidentified trophic interactions between invertebrates and
      thereby uncover pathways of pollutant spread. Here, we measured concentrations of
      the toxic metals lead, cadmium and mercury in carabid beetle predators and their
      prey. Invertebrates were sampled at one control and four heavy metal-polluted
      sites to reveal the impact of diet composition and seasonal variation in prey
      availability on metal burden in carabids and metal transfer pathways through
      forest ecosystems. This is the first report, to our knowledge, of carabid diet
      composition based on PCR analysis of gut contents at the forest community level,
      rather than in cultivated fields. Extensive screening using group- and species
      specific primers revealed that carabids ate primarily earthworms and slugs, as
      well as smaller numbers of woodlice and springtails. Metal concentrations in
      carabids correlated with seasonal changes in diet. Mercury accumulated in beetle
      predators more than in their slug prey. As earthworms, slugs and carabid beetles
      are the major prey of many birds and mammals, prey-predator transfer and
      associated toxicity are major risks at mercury-contaminated sites. Carabids may
      be useful bioindicators for assessing the impact of pollutants on soil
      ecosystems, as long as species and seasonal factors are taken into account.

PMID- 24138158
TI  - Cathodic electrodeposition of amorphous elemental selenium from an air- and water
      stable ionic liquid.
AB  - Electrodeposition of selenium from 1-propyl-1-methylpiperidinium
      bis(trifluoromethylsulfonyl)imide is reported. In situ UV-vis
      spectroelectrochemistry was used to investigate the reduction of diethyl selenite
      to form elemental selenium thin films from an ionic liquid-acetonitrile medium.
      Three reduction peaks of diethyl selenite were observed via cyclic voltammetry
      and are attributed to the stepwise reduction of the selenium precursor adsorbed
      on the electrode. The electrodeposition mechanism is influenced by both potential
      and time. Electrodeposition at -1.7 V vs Pt QRE resulted in the deposition of
      elemental selenium nanoparticles that with time coalesced to form a continuous
      film. At reduction potentials more negative than -1.7 V the morphology of the
      deposit changed significantly due to the reduction of elemental Se to Se(2-). In
      addition, p-type photoconductivity of the films was observed during the
      spectroelectrochemical measurements. X-ray diffraction and Raman spectroscopy
      confirmed that the deposited selenium films were amorphous. X-ray photoelectron
      spectroscopy and energy dispersive X-ray spectroscopy confirm the films consisted
      of pure selenium with minor residual contamination from the precursor and ionic
      liquid. 

PMID- 24138159
TI  - Binding-induced formation of DNA three-way junctions and its application to
      protein detection and DNA strand displacement.
AB  - DNA three-way junctions (DNA TWJs) are important building blocks to construct DNA
      architectures and dynamic assemblies. We describe here a binding-induced DNA TWJ
      strategy that is able to convert protein bindings to the formation of DNA TWJ.
      The binding-induced DNA TWJ makes use of two DNA motifs each conjugated to an
      affinity ligand. The binding of two affinity ligands to the target molecule
      triggers assembly of the DNA motifs and initiates the subsequent DNA strand
      displacement, resulting in a binding-induced TWJ. Real-time fluorescence
      monitoring of the binding-induced TWJ enables detection of the specific protein
      targets. A detection limit of 2.8 ng/mL was achieved for prostate-specific
      antigen. The binding-induced TWJ approach compares favorably with the toehold
      mediated DNA strand-displacement, the associative (combinative) toehold-mediated
      DNA strand-displacement, and the binding-induced DNA strand-displacement.
      Importantly, the binding-induced TWJ broadens the scope of dynamic DNA assemblies
      and provides a new strategy to design protein-responsive DNA devices and
      assemblies. 

PMID- 24138160
TI  - Premature or just small? Training Guatemalan birth attendants to weigh and assess
      gestational age of newborns: an analysis of outcomes.
AB  - We describe Guatemalan birth attendants' identification of vulnerable newborns,
      their evaluation of gestational age and anthropometry, and the validity of the
      Capurro and New Ballard newborn gestational age assessment methods. We
      interviewed 49 birth attendants and trained 10 of these women to assess 63
      newborns. The Capurro and Ballard methods were correlated (Spearman rho = .75, p
      < .001) and showed agreement (Bland-Altman plot, difference and bias, -0.33 +/-
      1.3 weeks). Prematurity was estimated at 27% (Ballard) and 24% (Capurro); low
      birth weight (LBW) was 30%. Capurro provided a simplified, equivalent estimate of
      gestational age compared with New Ballard that could be used by birth attendants.

PMID- 24138161
TI  - A new model for the biodegradation kinetics of oil droplets: application to the
      Deepwater Horizon oil spill in the Gulf of Mexico.
AB  - Oil biodegradation by native bacteria is one of the most important natural
      processes that can attenuate the environmental impacts of marine oil spills.
      Existing models for oil biodegradation kinetics are mostly for dissolved oil.
      This work developed a new mathematical model for the biodegradation of oil
      droplets and applied the model to estimate the time scale for oil biodegradation
      under conditions relevant to the Deepwater Horizon oil spill in the Gulf of
      Mexico. In the model, oil is composed of droplets of various sizes following the
      gamma function distribution. Each oil droplet shrinks during the microbe-mediated
      degradation at the oil-water interface. Using our developed model, we find that
      the degradation of oil droplets typically goes through two stages. The first
      stage is characterized by microbial activity unlimited by oil-water interface
      with higher biodegradation rates than that of the dissolved oil. The second stage
      is governed by the availability of the oil-water interface, which results in much
      slower rates than that of soluble oil. As a result, compared to that of the
      dissolved oil, the degradation of oil droplets typically starts faster and then
      quickly slows down, ultimately reaching a smaller percentage of degraded oil in
      longer time. The availability of the water-oil interface plays a key role in
      determining the rates and extent of degradation. We find that several parameters
      control biodegradation rates, including size distribution of oil droplets,
      initial microbial concentrations, initial oil concentration and composition.
      Under conditions relevant to the Deepwater Horizon spill, we find that the size
      distribution of oil droplets (mean and coefficient of variance) is the most
      important parameter because it determines the availability of the oil-water
      interface. Smaller oil droplets with larger variance leads to faster and larger
      extent of degradation. The developed model will be useful for evaluating
      transport and fate of spilled oil, different remediation strategies, and risk
      assessment. 

PMID- 24138162
TI  - Synthesis of enantioenriched tertiary boronic esters by the lithiation/borylation
      of secondary alkyl benzoates.
AB  - Simple, secondary 2,4,6-triisopropyl benzoates (TIB esters) and secondary dialkyl
      N,N-diisopropyl carbamates have been reported to be resistant to deprotonation by
      strong bases. We have found that the combination of sBuLi (1.6 equiv) and TMEDA
      (6 equiv) in CPME at -60  degrees C enables deprotonation of unactivated
      secondary dialkyl TIB esters, but not the carbamates. These carbanions were
      reacted with a range of neopentyl boronic esters which, after 1,2-metalate
      rearrangement and oxidation, gave a range of tertiary alcohols in high yield and
      universally high er. Further functional group transformations of the tertiary
      boronic esters were demonstrated (conversion to quaternary centers, C-tertiary
      amines) together with application of the methodology to the synthesis of the
      simplest unbranched hydrocarbon bearing a quaternary center, (R)-4-ethyl-4
      methyloctane, validating the synthetic utility of the methodology. 

PMID- 24138163
TI  - Dental handpiece contamination: a proteomics and surface analysis approach.
AB  - Dental handpieces (DHPs) become biofouled internally with patient derived
      material that is difficult to access for removal and inactivation. This study
      undertook a quantitative and qualitative investigation of protein contamination
      of internal components from three different types of DHP: the turbine, slow speed
      contra-angle and surgical. Eluates from the high speed turbine, low speed spray
      channels and surgical gear were assayed for protein using an orthophthaldehyde
      assay. Eluates concentrated by Amicon ultrafiltration were also analysed by SDS
      PAGE, mass spectroscopy, Western blotting and ELISA. The surfaces of handpiece
      components were also investigated by SEM, EFSCAN and EDAX microscopy. Surgical
      gears contained highest levels of protein (403 MUg), followed by low speed spray
      channels (17.7 MUg) and the high speed turbine (<5 MUg). Mass spectroscopy of
      surgical gears demonstrated mostly serum derived proteins. Decontamination of the
      DHPs using an automated washer disinfector and handpiece irrigator showed a
      significant reduction in residual protein levels. 

PMID- 24138164
TI  - A simple, scalable synthetic route to (+)- and (-)-pseudoephenamine.
AB  - A three-step synthesis of pseudoephenamine suitable for preparing multigram
      amounts of both enantiomers of the auxiliary from the inexpensive starting
      material benzil is described. The sequence involves synthesis of the crystalline
      monomethylimine derivative of benzil, reduction of that substance with lithium
      aluminum hydride, and resolution of pseudoephenamine with mandelic acid. 

PMID- 24138165
TI  - Characterization of the magnesium chelatase from Thermosynechococcus elongatus.
AB  - The first committed step in chlorophyll biosynthesis is catalysed by magnesium
      chelatase (E.C. 6.6.1.1), which uses the free energy of ATP hydrolysis to insert
      an Mg(2+) ion into the ring of protoporphyrin IX. We have characterized magnesium
      chelatase from the thermophilic cyanobacterium Thermosynechococcus elongatus.
      This chelatase is thermostable, with subunit melting temperatures between 55 and
      63 degrees C and optimal activity at 50 degrees C. The T. elongatus chelatase
      (kcat of 0.16 MUM/min) shows a Michaelis-Menten-type response to both Mg(2+) (Km
      of 2.3 mM) and MgATP(2-) (Km of 0.8 mM). The response to porphyrin is more
      complex; porphyrin inhibits at high concentrations of ChlH, but when the
      concentration of ChlH is comparable with the other two subunits the response is
      of a Michaelis-Menten type (at 0.4 MUM ChlH, Km is 0.2 MUM). Hybrid magnesium
      chelatases containing a mixture of subunits from the mesophilic Synechocystis and
      Thermosynechococcus enzymes are active. We generated all six possible hybrid
      magnesium chelatases; the hybrid chelatase containing Thermosynechococcus ChlD
      and Synechocystis ChlI and ChlH is not co-operative towards Mg(2+), in contrast
      with the Synechocystis magnesium chelatase. This loss of co-operativity reveals
      the significant regulatory role of Synechocystis ChlD.

PMID- 24138166
TI  - First analysis of the 1-v" progression of the Angstrom (B1Sigma+-A1Pi) band
      system in the rare 13C17O isotopologue.
AB  - The 1-v" progression of the Angstrom band system, so far unobserved in the rare
      (13)C(17)O isotopologue, was obtained under high resolution as an emission
      spectrum using a high accuracy dispersive optical spectroscopy. In the studied
      region 22,700-24,500 cm(-1), 146 spectral lines were observed, among which 118
      were interpreted as belonging to the 1-0 and 1-1 bands of B-A system, and the
      next 28 were interpreted as extra lines belonging to the 1-1 band of B(1)Sigma(+)
      e(3)Sigma(-) intercombination system, also unobserved in the (13)C(17)O molecule
      so far. All those lines were precisely measured with an estimated accuracy better
      than 0.0025 cm(-1), and rotationally analyzed. As a result the following in the
      (13)C(17)O molecule were calculated for the first time: the merged rotational
      constants B1 = 1.790227(23) cm(-1), D1 = 6.233(47) * 10(-6) cm(-1), and DeltaG1/2
      = 2010.9622 (69) cm(-1) and the equilibrium constants, omegae = 2076.04(57) cm(
      1), omegaexe = 32.54(28) cm(-1), Be = 1.824678(15) cm(-1), alphae = 2.2967(24) *
      10(-2) cm(-1), De = 5.226(25) * 10(-6) cm(-1), and betae = 6.71(48) * 10(-7) cm(
      1) for the B(1)Sigma(+) Rydberg state, as well as the individual rotational
      constant B0 = 1.50485(78) cm(-1), and the equilibrium constants omegae =
      1463.340(21) cm(-1), Be = 1.49902(12) cm(-1), alphae = 1.7782(49) * 10(-2) cm(
      1), De = 7.36(56) * 10(-6) cm(-1) for the A(1)Pi state, and sigmae =
      21,854.015(51) cm(-1), RKR turning points, Franck-Condon factors (FCF), relative
      intensities, and r centroids for the Angstrom band system. With the help of the
      strong and vast A(1)Pi (v = 0) ~ e(3)Sigma(-) (v = 1) interaction, the
      experimental parameters of the e(3)Sigma(-) (v = 1) perturbing state were
      established in the (13)C(17)O molecule for the first time.

PMID- 24138167
TI  - Anti-inflammatory potency of nano-formulated puerarin and curcumin in rats
      subjected to the lipopolysaccharide-induced inflammation.
AB  - Puerarin (PU) and curcumin (CU), used commonly in traditional Chinese medicine
      and Ayurveda, have been shown to possess potent anti-inflammatory, anti
      oxidation, and neuro-protective properties. Despite the experimental success of
      CU and PU in in vitro and animal models, their effectiveness has not yet been
      demonstrated in clinical trials, possibly because of their poor bioavailability.
      We hypothesized that gold nanoparticle (AuNP)-formulated PU (PU-AuNP), CU (CU
      AuNP), or a combination of PU and CU (PU-CU-AuNP) were a more effective and
      nontoxic alternative to their bulk (nonformulated) counterparts. To test the
      hypothesis, bioavailability, therapeutic potency, and toxicity of bulk CU and/or
      PU were compared with those of their nanotized counterparts in rats subjected to
      the lipopolysaccharide (LPS)-induced inflammation. This study showed that a 20
      mg/kg dose of bulk PU or a mixture of PU and CU did not, while their nanotized
      counterparts, PU-AuNP, CU-AuNP, or PU-CU-AuNP, effectively suppressed the LPS
      induced inflammation and cytotoxicity in rats. In addition, PU-CU-AuNP was more
      potent than PU-AuNP or CU-AuNP alone. The blank AuNP (bAuNP) at <=40 mg/kg dose
      did not cause any adverse effects (blood and brain lactic acid concentrations,
      kidney function, and neuronal apoptosis were measured) in animals. Therefore, the
      present observations suggest that a bi-functional AuNP loaded with CU and PU may
      effectively suppress the LPS-induced inflammation and cytotoxicity provided the
      following conditions are met: (1) The AuNP dose is at or below the no-effect
      dose; (2) the nanoparticles release a therapeutic dose of CU and PU in vivo; and
      (3) the active ingredients are released into the intracellular component of the
      brain.

PMID- 24138168
TI  - Neuroprotective effect of lutein against 3-nitropropionic acid-induced
      Huntington's disease-like symptoms: possible behavioral, biochemical, and
      cellular alterations.
AB  - 3-Nitropropionic acid (3-NP) induces cellular energy deficit and oxidative stress
      related neurotoxicity via an irreversible inhibition of mitochondrial complex II
      enzyme, succinate dehydrogenase. Huntington's disease (HD) is a neurological
      disorder characterized by cognitive and motor dysfunctions. Lutein is a well
      known antioxidant used in the management of oxidative stress related diseases.
      Clinical trials have supported the beneficial effect of lutein in Alzheimer's
      disease. The present study was designed to explore possible neuroprotective
      effects of lutein on 3-NP-induced mitochondrial dysfunction and oxidative stress.
      Systemic administration of 3-NP (25 mg/kg intraperitoneally [i.p.] for 4
      consecutive days) caused loss of body weight and neurobehavioral deficits by hind
      limb impairment (Narrow Beam test), motor coordination (locomotor activity) and
      memory dysfunction (Morris water maze and Elevated Plus maze performance).
      Biochemical analysis revealed significant increase in lipid peroxidation, nitrite
      concentration, reduced gutathione levels, and acetyl cholinesterase levels and
      depleted catalase activities in rat brain. The activities of mitochondrial
      complexes (I, II, IV, and MTT assay) were found to be significantly lowered in
      brain mitochondria. Daily lutein (50 or 100 mg/kg orally [p.o.]) administration
      for 14 days significantly improved body weight, neurobehavioral alterations and
      attenuated oxidative stress and improved mitochondrial enzymes complex activities
      of rat brain. Histopathological examination further affirmed the neuroprotective
      effect of lutein on 3-NP induced pathological lesions. The present study
      indicates that lutein is a promising candidate for the management of HD and
      related conditions.

PMID- 24138169
TI  - Dissecting the effect of RNA aptamer binding on the dynamics of plasminogen
      activator inhibitor 1 using hydrogen/deuterium exchange mass spectrometry.
AB  - RNA aptamers, selected from large synthetic libraries, are attracting increasing
      interest as protein ligands, with potential uses as prototype pharmaceuticals,
      conformational probes, and reagents for specific quantification of protein levels
      in biological samples. Very little is known, however, about their effects on
      protein conformation and dynamics. We have employed hydrogen/deuterium exchange
      (HDX) mass spectrometry to study the effect of RNA aptamers on the structural
      flexibility of the serpin plasminogen activator inhibitor-1 (PAI-1). The aptamers
      have characteristic effects on the biochemical properties of PAI-1. In
      particular, they are potent inhibitors of the structural transition of PAI-1 from
      the active state to the inactive, so-called latent state. This transition is one
      of the largest conformational changes of a folded protein domain without covalent
      modification. Binding of the aptamers to PAI-1 is associated with substantial and
      widespread protection against deuterium uptake in PAI-1. The aptamers induce
      protection against exchange with the solvent both in the protein-aptamer
      interface as well as in other specific areas. Interestingly, the aptamers induce
      substantial protection against exchange in alpha-helices B, C and I. This
      observation substantiates the relevance of structural instability in this region
      for transition to the latent state and argues for involvement of flexibility in
      regions not commonly associated with regulation of latency transition in serpins.

PMID- 24138170
TI  - Antimicrobial blue light: an emerging alternative to antibiotics.

PMID- 24138171
TI  - Antimicrobial potential of metabolites extracted from bacterial symbionts
      associated with marine sponges in coastal area of Gulf of Mannar Biosphere,
      India.
AB  - Marine coastal areas of India have vast diversity of sponges which harbours many
      endosymbiotic bacteria which are the source of many potential antimicrobial
      metabolites. This study focuses the screening and characterization of drug
      producing bacteria symbiotically which are associated with marine sponges
      collected from Gulf of Mannar, South Coast India. Six different sponges were
      collected and they were identified on the basis of their morphology. The drug
      producing isolates were screened by agar overlay method towards various clinical
      strains. The secondary metabolites were characterized and were found to be
      quinones, alkaloids, flavanoids and flavonyl glycosides. The metabolites showed
      significant inhibitory properties against clinical strains that were further
      identified as chromophoric and fluorophoric in nature. Ethyl acetate extracts of
      chromophore and floureophore substances showed significant inhibitory properties
      against Methicillin resistant Staphylococcus aureus (MRSA) and Salmonella typhi
      respectively. 16S rRNA gene sequencing of theses isolates revealed that
      chomophore-producing strain were closely related to Pseudomonas spp. RHLB12,
      isolated from Callyspongia spp. and floureophore-producing bacteria was related
      to Bacillus licheniformis T6-1 which was isolated from Haliclona spp. Hence, our
      study demonstrated that antimicrobial metabolites extracted from symbiotic
      bacteria associated with marine sponges have high therapeutic potential against
      many bacterial pathogens including multidrug-resistant strains. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This is the first study demonstrating antimicrobial
      potential of flurophoric and chromophoric metabolites extracted from bacterial
      biosymbionts associated with marine sponges. Our study has significant scope as
      Indian coastal area especially harbours vast varieties of sponges with novel
      secondary metabolites-producing organisms. The natural metabolites extracted from
      sponge-derived bacteria pave novel therapeutic remedy against various pathogens
      when most of them are emerged as extreme drug resistant superbugs.

PMID- 24138172
TI  - Phosphorylation of a p38-like MAPK is involved in sensing cellular redox state
      and drives atypical tubulin polymer assembly in angiosperms.
AB  - Reactive oxygen species (ROS) imbalance is a stressful condition for plant cells
      accompanied by dramatic changes in tubulin cytoskeleton. Here, evidence is
      provided that alterations in ROS levels directly interfere with the
      phosphorylation state of a p38-like MAPK in the angiosperms Triticum turgidum and
      Arabidopsis thaliana. Both oxidative stress generators and chemicals inducing ROS
      scavenging or decreasing ROS production resulted in the accumulation of a phospho
      p46 protein similar to p38-MAPK. Importantly, the rhd2 A. thaliana mutants
      exhibited a remarkable increase in levels of phospho-p46. The presence of the p38
      MAPK inhibitor SB203580 attenuated the response to ROS disturbance, prevented
      microtubule disappearance and resulted in a dramatic decrease in the number of
      atypical tubulin polymers. Moreover, in roots treated simultaneously with
      substances inducing ROS overproduction and others resulting in low ROS levels,
      phospho-p46 levels and the organization of tubulin cytoskeleton were similar to
      controls. Collectively, our experimental data suggest, for the first time in
      plants, that p46 functions as a putative sensor of redox state, the activation of
      which initiates downstream signalling events leading to microtubule disruption
      and subsequent assembly of atypical tubulin polymers. Thus, p46 seems to
      participate in perception of ROS homeostasis disturbance as well as in cellular
      responses to redox imbalance. 

PMID- 24138173
TI  - Divergence in threat sensitivity among aquatic larvae of cryptic mosquito
      species.
AB  - Predation is a major evolutionary force driving speciation. The threat-sensitive
      response hypothesis predicts that prey adjust and balance the time spent on a
      costly antipredator response with other activities that enhance their fitness.
      Thus, prey able to develop an antipredator response proportional to risk
      intensity should have a selective advantage. Knowledge on how evolution has
      shaped threat sensitivity among closely related species exposed to different
      predation pressures is scarce, prompting investigations to better predict and
      explain its effect on communities. We explored and compared the antipredator
      response of aquatic mosquito larvae in three sibling species of the Anopheles
      gambiae complex, with contrasting larval biologies in Burkina Faso. Anopheles
      arabiensis and An. gambiae sensu stricto breed in temporary water collections
      where predator densities are low, whereas Anopheles coluzzii is able to thrive in
      permanent pools where the predation pressure is much higher. We hypothesized that
      the increase and decline of behavioural antipredator responses might differ
      between the three species over time. To test this hypothesis, progenies of field
      collected mosquitoes were experimentally exposed to a range of soluble predation
      cues and their response was monitored for up to 48 h. The three species were all
      threat sensitive but their reaction norms differed. For the range of
      concentrations tested, An. coluzzii larvae gradually increased in antipredator
      response, whereas An. gambiae larvae readily displayed antipredator behaviour at
      low concentrations leading to a saturation of the response for high cue
      concentrations. An. arabiensis displayed a narrower reaction norm with low
      response intensity. Larval instars did not differ in their threat sensitivity.
      The antipredator behaviour of the three species waned after about 1 h of
      exposure. Early instars tended to express antipredation behaviour for longer than
      did older instars. This study provides information on how aquatic prey species
      with an aerial adult stage manage larval predation risk over time according to
      cue concentrations and suggests that different predation pressures might play a
      role as a disruptive selective force fostering habitat segregation and speciation
      within the An. gambiae complex. The evolution of phenotypic plasticity is further
      discussed in the light of divergent predation pressures.

PMID- 24138174
TI  - How beneficial is the use of NSAIDs in stem-cell transplantation?
AB  - For a number of malignant hematologic diseases, including leukemias, lymphomas
      and myelomas, hematopoietic stem cell transplantation remains the only curative
      option. The stem cell sources for these life-saving transplants come from bone
      marrow, umbilical cord blood, or from the peripheral blood of patients or donors
      treated with mobilizing agents. Recently, the use of nonsteroidal anti
      inflammatory drugs (NSAIDs) including aspirin, ibuprofen and meloxicam has been
      reported to enhance the ability to acquire stem cells from mobilized peripheral
      blood, resulting in a superior stem cell graft. The addition of NSAIDs, notably
      meloxicam, to current mobilization strategies is convenient, cost effective, and
      given the long track record of NSAID use, presumably safe. This article discusses
      the potential to translate these findings to clinical practice and addresses
      unanswered questions regarding the use of NSAIDs in stem cell transplantation. 

PMID- 24138175
TI  - Does life history mediate changing disease risk when communities disassemble?
AB  - Biodiversity loss sometimes increases disease risk or parasite transmission in
      humans, wildlife and plants. Some have suggested that this pattern can emerge
      when host species that persist throughout community disassembly show high host
      competence - the ability to acquire and transmit infections. Here, we briefly
      assess the current empirical evidence for covariance between host competence and
      extirpation risk, and evaluate the consequences for disease dynamics in host
      communities undergoing disassembly. We find evidence for such covariance, but the
      mechanisms for and variability around this relationship have received limited
      consideration. This deficit could lead to spurious assumptions about how and why
      disease dynamics respond to community disassembly. Using a stochastic simulation
      model, we demonstrate that weak covariance between competence and extirpation
      risk may account for inconsistent effects of host diversity on disease risk that
      have been observed empirically. This model highlights the predictive utility of
      understanding the degree to which host competence relates to extirpation risk,
      and the need for a better understanding of the mechanisms underlying such
      relationships. 

PMID- 24138176
TI  - Porphyrin assemblies and their scaffolds.
AB  - The chlorophyll and heme molecules of chloroplasts and mitochondria are brought
      to life by "the global fold of the protein scaffolds". Proteins in hydrophobic
      cell regions touch the dye platelets from both sides, pushing and orienting them
      according to their life-spending activities in light and electron transfers. The
      conjugated pi-electron systems or planarity of the porphyrin macrocycles are
      never disturbed. Most artificial porphyrin assemblies contain meso
      tetraphenylporphyrins (TPPs), because the four phenyl groups rotate freely and
      carry their substituents above or below the macrocycle. A single porphyrin
      molecule can, for example, be attached to an anionic surface with ammonium groups
      on its 2,3-carbons, be located within a hydrophobic membrane with its alkyl
      chains on the 4-position, and then fixate a cationic polymer with 4,5
      sulphonates. Charged TPPs also show unique spectroscopic changes at different pH
      values and a reversible loss of the macrocycle's planarity. On smooth silicate,
      graphite, or gold scaffolds TPPs have been attached irreversibly as single
      molecules, as extended non-covalent H or J aggregates as well as acetylene or
      thiophene-linked polymers. Soft, mobile porphyrin ladders conduct excited
      electrons ("excitons") better than rigid porphyrin wires ("polarons"). 

PMID- 24138177
TI  - RETRACTED: Different bone mineral density in cervical and endometrial cancer.
AB  - Objectives Patients with cervical cancer have lower bone mass than women without
      cancer, whereas women with endometrial cancer have higher bone mineral density
      (BMD) than control subjects, possibly due to the prevalence of high body-fat
      mass. The aim of this study was to compare BMD in patients with cervical cancer,
      endometrial cancer and controls. Methods We analyzed and compared spinal and
      femoral BMD in 130 patients with cervical cancer, 68 with endometrial cancer, and
      140 age-matched menopausal female control subjects. We also compared serum
      calcium, phosphorus, total alkaline phosphatase, osteocalcin, and urinary
      deoxypyridinoline levels. Results Compared with the control group, T-scores for
      some lumbar vertebrae (L4), the femoral neck, and Ward's triangle were lower in
      patients with cervical cancer, whereas only L4 T-scores were significantly lower
      in patients with endometrial cancer. Deoxypyridinoline levels were significantly
      lower in women with endometrial cancer (p < 0.002) than in women with cervical
      cancer, but no other biochemical variables differed among groups. Conclusions
      Cervical cancer was associated with lower BMD, especially in femoral BMD, and may
      be a risk factor for secondary osteoporosis. However, endometrial cancer
      generally seemed to have no damaging effect on bone except at L4. A further
      larger follow-up study in more populations is required to clarify these findings.

PMID- 24138178
TI  - Risk-related and protective correlates of nonsuicidal self-injury and co
      occurring suicide attempts among incarcerated women.
AB  - Individual and environmental correlates of nonsuicidal self-injury (NSSI) and co
      occurring suicide attempts (SA) among incarcerated women (N = 104) were examined.
      Participants completed measures of putative risk and protective factors,
      including coping styles, childhood maltreatment, and hopelessness. Results
      indicated that active coping was uniquely, negatively associated with the
      presence and frequency of NSSI, whereas avoidant coping and childhood
      physical/emotional abuse were positively associated with NSSI frequency.
      Conversely, among women with a history of NSSI, hopelessness was uniquely,
      positively associated with the presence and frequency of SA. Further, childhood
      sexual abuse was associated with the presence of SA, while physical/emotional
      abuse was associated with SA frequency. Hopelessness was more strongly related to
      SA frequency than NSSI frequency. These findings help disentangle the unique risk
      and protective factors for NSSI and co-occurring SA in incarcerated samples. 

PMID- 24138179
TI  - In vitro and in vivo evaluation of porous PCL-PLLA 3D polymer scaffolds
      fabricated via salt leaching method for bone tissue engineering applications.
AB  - Three dimensional porous scaffolds composed of various ratios of polycaprolactone
      and poly(L-lactic acid) (PLLA) were prepared using salt leaching method for bone
      regeneration applications. Surfaces of the scaffolds were visualized using
      scanning electron microscope (SEM) and the combination of the polymers was
      confirmed by FT-IR. Addition of PLLA increased the porosity and pore sizes of the
      scaffolds and also the scaffolds' compressive strength initially. Osteoblast-like
      cells were used and it was found that the samples' cell biocompatibility was
      further promoted with the increase in PLLA content as observed via cell
      proliferation assays using MTT, gene expression with RT-PCR, and micrographs from
      SEM and confocal microscopy. Samples were then implanted into male rabbits for 2
      months, and histological staining and micro-CT histomorphometry show that new
      bone formations were detected in the site containing the implants of the
      scaffolds and that bone regeneration was further promoted with the increased
      concentration of PLLA in the scaffold.

PMID- 24138180
TI  - Some smart approaches to a tough problem.

PMID- 24138181
TI  - Meeting the geriatric workforce shortage for long-term care: opinions from the
      field.
AB  - This article seeks to raise awareness of workforce issues among geriatricians in
      caring for the increasing number of older Americans with disabilities who will
      need long-term care. Using a snowball sampling technique, telephone or in-person
      interviews were conducted with 10 geriatricians to obtain providers' perspectives
      of the challenges of having an adequate supply of qualified physicians working in
      Texas nursing homes. Speaking from experience (these geriatricians had an average
      of 15 years of work experience in nursing homes), the geriatric experts reflected
      upon reasons for choosing (or not) geriatric medicine; reasons for choosing (or
      not) to work in nursing homes; and the status of geriatrics in the United States.
      To meet the increasing demand for nursing home services, the findings of this
      article suggest strengthening support for the geriatrician workforce. Specific
      recommendations for training the next generation of geriatricians are presented. 

PMID- 24138182
TI  - Preparing to care for an aging population: medical student reflections on their
      clinical mentors within a new geriatrics curriculum.
AB  - Reflective writing techniques such as journaling help provide insights into the
      process by which medical students are mentored and develop into practicing
      physicians. The authors sought to analyze medical students' journals regarding
      their mentored experiences within a new geriatrics curriculum at a U.S. medical
      school. Thirty preclinical and clinical medical student journalers participated
      in this project. The authors employed qualitative analytic techniques using an
      interdisciplinary team process. Three major themes emerged: (a) exposure to
      clinical mentors challenged medical students' preconceptions regarding older
      adults and geriatric medicine; (b) students learned new medical knowledge and
      techniques from observing their mentors; and (c) students provided positive and
      negative assessments of their mentors. Reflective journaling provides important
      insights into the process by which medical students draw upon mentored clinical
      experiences during their training. Such mentorship may be particularly relevant
      to promoting their interest in geriatrics. 

PMID- 24138185
TI  - A turn-on fluorescent sensor for sensitive and selective detection of sodium
      dodecyl sulfate based on the eosin Y/polyethyleneimine system.
AB  - A novel sensing system has been designed for the detection of sodium dodecyl
      sulfate (SDS) based on the recovered fluorescence signal of eosin Y and
      polyethyleneimine (PEI) complex. The eosin Y reacted with PEI to form a complex
      by virtue of hydrophobic interaction as well as the electrostatic interaction,
      which resulted in a strong fluorescence quenching of the eosin Y. Subsequently,
      with the addition of SDS to the eosin Y/PEI system, a strong surface interaction
      and electrostatic interactions between PEI and SDS resulted in the formation of
      the PEI/SDS complex and the dissociation of the eosin Y/PEI complex, which led to
      the significant fluorescence recovery. Herein, we have demonstrated that this
      facile methodology can offer a rapid, reliable, and selective detection of SDS
      with a detection limit as low as 0.02 MUg mL(-1) and a linear range from 0.4 to 6
      MUg mL(-1). Furthermore, the method has been successfully applied to the
      detection of SDS in real samples with satisfied recovery and accuracy. Overall,
      these results demonstrate that this method has great promise for environmental
      applications. 

PMID- 24138186
TI  - Prevalence of cardiovascular risk factors among adults without obvious
      cardiovascular disease in a rural community in Ekiti State, Southwest Nigeria.
AB  - BACKGROUND: Cardiovascular disease worldwide is largely driven by modifiable risk
      factors. This study sought to identify and determine the prevalence of
      traditional cardiovascular risk factors according to sex in inhabitants of a
      rural community in a developing country. METHODS: This cross-sectional study
      included participants aged >=40 years in the rural community of Aaye Ekiti, Ekiti
      State, Southwest Nigeria. All participants who met the inclusion criteria were
      drawn from the 161 households in the community. Data on the following were
      collected: arterial hypertension, diabetes mellitus, obesity, dyslipidaemia,
      smoking, physical activity, alcohol consumption, and sociodemographic parameters.
      These were analysed with SPSS version 16.0 software. RESULTS: The 104
      participants (33 male, 71 female) had a mean age (+/- standard deviation) of
      66.77 +/- 12.06 years (range, 40-88 years). The majority of the participants
      (56.7%) were aged 60-79 years. Hypertension was present in 66.4%, diabetes
      mellitus in 4.8%, abdominal obesity in 38.46%, smoking in 2.9%, physical
      inactivity in 29.8%, and high alcohol consumption in 1%. Dyslipidaemia, as
      represented by low HDL-C, occurred in 30%. There were borderline high levels of
      TC in 4.5%, LDL-C in 1.1%, and TG in 12.5%, but no subject had a high level.
      Abdominal obesity, alcohol consumption and smoking were statistically
      significantly associated with sex. CONCLUSION: In this study, traditional
      cardiovascular risk factors, apart from hypertension, obesity, physical
      inactivity and low HDL-C had a low prevalence in the rural Nigerian community.
      However, the high prevalence of hypertension in this poor community suggests a
      high risk of a future cardiovascular event.

PMID- 24138187
TI  - Enantio- and diastereoselective synthesis of syn-beta-hydroxy-alpha-vinyl
      carboxylic esters via reductive aldol reactions of ethyl allenecarboxylate with
      10-TMS-9-Borabicyclo[3.3.2]decane and DFT analysis of the hydroboration pathway.
AB  - An enantio- and diastereoselective synthesis of syn-beta-hydroxy-alpha-vinyl
      carboxylate esters 3 via the reductive aldol reaction of ethyl allenecarboxylate
      (2) with 10-trimethylsilyl-9-borabicyclo[3.3.2]decane (1R) has been developed.
      Density functional theory calculations suggest that the allene hydroboration
      involves the 1,4-reduction of 2 with the 1R, leading directly to dienolborinate Z
      (O)-8a. 

PMID- 24138188
TI  - Tourette syndrome and chronic tic disorder are associated with lower socio
      economic status: findings from the Avon Longitudinal Study of Parents and
      Children cohort.
AB  - AIM: Only a few studies have examined the relationship between Tourette syndrome
      or chronic tic disorder and socio-economic status (SES). Existing studies are
      primarily cross-sectional, arise from specialty clinics, and use single measures
      of SES. In this study we examine this relationship in a longitudinal, population
      based sample. METHOD: Data are from 7152 children born during 1991 and 1992 in
      the county of Avon, UK, from the Avon Longitudinal Study of Parents and Children,
      who were followed up to age 13. After exclusions for intellectual disability* and
      autism, 6768 participants (3351 males [49.5%]) and 3417 females [50.5%])
      remained. Parental SES was assessed using multiple measures during pregnancy and
      at 33 months of age. Presence of Tourette syndrome or chronic tics was determined
      from repeated maternal questionnaires up to when the child was 13 years of age.
      RESULTS: Multiple SES measures were associated with an approximately twofold
      increased risk of Tourette syndrome and chronic tics. A postnatal composite
      factor score (lowest vs highest tertile odds ratio 2.09, 95% confidence interval
      1.38-3.47) provided the best fit to the data. INTERPRETATIONS: As is seen in
      several childhood conditions, such as cerebral palsy and autism, lower SES is a
      risk factor for Tourette syndrome/chronic tics. Potential explanations include
      differential exposure to environmental risk factors or parental psychopathology
      as a measure of an increased genetic risk leading to decreased parental SES.

PMID- 24138189
TI  - The dermomyotome ventrolateral lip is essential for the hypaxial myotome
      formation.
AB  - BACKGROUND: The myotome is the primitive skeletal muscle that forms within the
      embryonic metameric body wall. It can be subdivided into an epaxial and hypaxial
      domain. It has been shown that the formation of the epaxial myotome requires the
      dorsomedial lip of the dermomyotome (DML). Although the ventrolateral lip (VLL)
      of the dermomyotome is believed to be required for the formation of the hypaxial
      myotome, experimentally evidence for this statement still needs to be provided.
      Provision of such data would enable the resolution of a debate regarding the
      formation of the hypaxial dermomyotome. Two mechanisms have been proposed for
      this tissue. The first proposes that the intermediate dermomyotome undergoes
      cellular expansion thereby pushing the ventral lateral lip in a lateral direction
      (translocation). In contrast, the alternative view holds that the ventral lateral
      lip grows laterally. RESULTS: Using time lapse confocal microscopy, we observed
      that the GFP-labelled ventrolateral lip (VLL) of the dermomyotome grows rather
      than translocates in a lateral direction. The necessity of the VLL for lateral
      extension of the myotome was addressed by ablation studies. We found that the
      hypaxial myotome did not form after VLL ablation. In contrast, the removal of an
      intermediate portion of the dermomyotome had very little effect of the hypaxial
      myotome. These results demonstrate that the VLL is required for the formation of
      the hypaxial myotome. CONCLUSION: Our study demonstrates that the dermomyotome
      ventrolateral lip is essential for the hypaxial myotome formation and supports
      the lip extension model. Therefore, despite being under independent signalling
      controls, both the dorsomedial and ventrolateral lip fulfil the same function,
      i.e. they extend into adjacent regions permitting the growth of the myotome.

PMID- 24138190
TI  - Atomic force microscopic evaluation of nanostructure alterations of rotary NiTi
      instruments after immersion in irrigating solutions.
AB  - AIM: To compare the effect of 5.25% NaOCl or 17% EDTA solutions on the surface
      topography and roughness of GTX, TF, RaCe and Hero Shaper instruments using
      atomic force microscopy (AFM) analysis. METHODOLOGY: Four new files of each brand
      were subjected to AMF analysis; then each group was subdivided into two subgroups
      (n = 2) in which instruments were immersed in either 5.25% NaOCl or 17% EDTA
      solutions for 5 min, thereafter subjected to AFM analysis again. Ra and the RMS
      values were chosen to investigate the surface features of endodontic files.
      RESULTS: Before immersion in irrigating solution, TF and Hero Shaper instruments
      had the significantly highest roughness values and RaCe had the significantly
      lowest values (P <= 0.05). After immersion in NaOCl, GTX and RaCe instruments
      were not significantly different from the new instruments, nor between them.
      There was a significant increase in Ra and RMS values for TF and Hero Shaper
      instruments over that of untreated ones and that of GTX and RaCe instruments. No
      significant increase in surface roughness of the instruments was recorded with
      EDTA. CONCLUSION: 17% EDTA did not significantly affect the surface roughness of
      the instruments, whilst 5.25% NaOCl increased the surface roughness of TF and
      Hero Shaper significantly more than that of RaCe and GTX instruments.

PMID- 24138191
TI  - Preliminary assessment of photoactivated antimicrobial collagen on bioburden in a
      murine pressure ulcer model.
AB  - OBJECTIVE AND BACKGROUND DATA: Overcoming bacterial antibiotic resistance
      requires alternative strategies. The ability of photoactivated collagen-embedded
      flavins (PCF) to reduce bioburden in infected pressure ulcers was investigated.
      DESIGN AND METHODS: Two pressure ulcers were created on the dorsum of female
      BALB/C mice (n=40, 35 g) maintaining a 5 mm skin bridge between lesions. Ulcers
      and surrounding skin were covered with TegadermTM and inoculated with 0.1 mL of 1
      * 10(5) colony-forming units (CFU)/mL methicillin-resistant Staphylococcus aureus
      (MRSA). Fluid was permitted to reabsorb for 10 min. In experiment 1, one wound
      from each animal was treated using PCF and photoradiation (PCF+R, n=12) or
      photoradiation alone (R, n=11). Composite dressing-treated wounds received 1 * 1
      cm PCF discs. Overlying Tegaderm was excised, and PCF was placed over the wound
      and again covered with Tegaderm. Wounds were irradiated at 455 +/- 5 nm (350 mW,
      1 cm spot diameter, 15 min) using a diode laser 10 min after placement. Controls
      received no PCF or photoradiation (C, n=12). Animals were euthanized 24 h post
      therapy. Quantitative bacterial counts (CFU/g tissue) were determined. In
      experiment 2, composite dressing-treated wounds were irradiated at 455 +/- 5 nm
      (350 mW, 1 cm spot diameter, 15 min) using a diode laser 10 min after daily PCF
      placement (0, 1, 2, or 3 treatments, n=8/group). Controls received no treatment.
      Wounds were cultured daily. Animals were euthanized on day 7 post-infection.
      Quantitative bacterial counts were determined. RESULTS: PCF+R significantly
      reduced bacterial counts at 24 h (experiment 1, p<0.0001; experiment 2, p<0.05).
      The bacterial counts in rats receiving photoradiation alone were no different
      from those of untreated controls (experiment 1, p=0.24). PCF+R produced a 2-3 log
      reduction in bacterial counts (experiment 2, p<0.001). Antibacterial effects
      increased with number of treatments, and persisted for several days post-therapy
      (p<0.002). CONCLUSIONS: PCF+R inhibited bacterial growth in this model. This
      effect increased with successive treatments, persisting several days post
      therapy. Further studies to optimize this treatment modality are warranted.

PMID- 24138192
TI  - Does photodynamic therapy enhance standard antibacterial therapy in dentistry?
AB  - OBJECTIVE: The aim of this study was to assess whether or not photodynamic
      therapy enhanced standard antibacterial therapy in dentistry. BACKGROUND DATA:
      Photodynamic therapy when used as an adjunct to conventional periodontal therapy
      kills more bacteria than when conventional periodontal therapy is used alone.
      MATERIALS AND METHODS: To address the focused question, "Does photodynamic
      therapy enhance killing of oral bacteria?" PubMed/MEDLINE((r)) and Google Scholar
      databases were explored. Original human and experimental studies and studies
      using photodynamic therapy for killing oral bacteria were included. Letters to
      the Editor, historic reviews, and unpublished data were excluded. RESULTS:
      Photodynamic therapy significantly reduces periodontopathogenic bacteria
      including Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and
      Porphyromonas gingivalis. Photodynamic therapy kills cariogenic bacteria (such as
      Streptococcus mutans and Streptococcus sanguis), bacteria associated with
      infected root canals, and those associated with periimplantitis. CONCLUSIONS:
      Photodynamic therapy, when used as an adjunct to conventional oral disinfection
      protocols, enhances standard antibacterial therapy in dentistry.

PMID- 24138193
TI  - In vitro bactericidal effects of 625, 525, and 425 nm wavelength (red, green, and
      blue) light-emitting diode irradiation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship of 625,
      525, and 425 nm wavelengths, providing average power output and effects on three
      common pathogenic bacteria. BACKGROUND DATA: Ultraviolet (UV) light kills
      bacteria, but the bactericidal effects of UV may not be unique, as 425 nm
      produces a similar effect. The bactericidal effects of light-emitting diode (LED)
      wavelengths such as 625 and 525 nm have not been described. Before conducting
      clinical trials, the appropriate wavelength with reasonable dose and exposure
      time should be established. MATERIALS AND METHODS: The bactericidal effects of
      625, 525, and 425 nm wavelength LED irradiation were investigated in vitro for
      the anaerobic bacterium Porphyromonas gingivalis and two aerobes (Staphylococcus
      aureus and Escherichia coli DH5alpha). Average power output was 6 mW/cm(2) for 1
      h. The bacteria were exposed to LED irradiation for 1, 2, 4, and 8 h (21.6, 43.2,
      86.4, and 172.8 J/cm(2), respectively). LED irradiation was performed during
      growth on agar and in broth. Control bacteria were incubated without LED
      irradiation. Bacterial growth was expressed in colony-forming units (CFU) and at
      an optical density at 600 nm in agar and broth. RESULTS: The bactericidal effect
      of LED phototherapy depended upon wavelength, power density, bacterial viable
      number, and bacteria species. The bactericidal effect of 425 and 525 nm
      irradiation varied depending upon the bacterial inoculation, compared with
      unirradiated samples and samples irradiated with red light. Especially, P.
      gingivalis and E. coli DH5alpha were killed by 425 nm, and S. aureus growth was
      inhibited by 525 nm. However, the wavelength of 625 nm was not bactericidal for
      P. gingivalis, E. coli DH5alpha, or S. aureus. CONCLUSIONS: Irradiation at 625 nm
      light was not bactericidal to S. aureus, E. coli, and P. gingivalis, whereas
      wavelengths of 425 and 525 nm had bactericidal effects. S. aureus was also killed
      at 525 nm.

PMID- 24138194
TI  - Oversecretion of soluble CTLA-4 in various autoimmune diseases overlapping celiac
      disease.
AB  - AIM: To evaluate the levels of soluble CTLA-4 (sCTLA-4) in sera of celiac disease
      (CD) patients with overlapping autoimmune diseases (OAD; diabetes mellitus,
      autoimmune thyroid diseases, inflammatory bowel diseases, and autoimmune
      polyendocrine syndromes). METHODS: Sera from Italian patients with CD were
      obtained and enzyme-linked immunosorbent assay was used to measure sCTLA-4.
      RESULTS: Consistently high serum sCTLA-4 levels were observed in CD (13.20 ng/mL,
      p<0.0001) and OAD (19.48 ng/mL, p<0.0001) compared to normal controls. A
      significant increase in the level of serum sCTLA-4 was observed in OAD (p=0.0273)
      compared to CD alone. At variance, no significant difference in the sCTLA-4
      levels was observed when single OAD were compared. CONCLUSION: The present study
      shows for the first time a statistically significant increase of serum sCTLA-4
      levels in CD patients with associated autoimmune disease (namely, CD and OAD)
      versus patients with CD alone. Previously, the potential genetic associations of
      several CTLA-4 polymorphisms to susceptibility to autoimmune diseases have been
      described, although the relationship between CTLA-4 polymorphisms and the ability
      to produce the soluble form is not fully clarified. CTLA-4 is a strong actor in
      the adaptive response: our data give supportive evidence of the common background
      of autoimmune diseases.

PMID- 24138195
TI  - Independent domestications of cultivated tree peonies from different wild peony
      species.
AB  - An understanding of plant domestication history provides insights into general
      mechanisms of plant adaptation and diversification and can guide breeding
      programmes that aim to improve cultivated species. Cultivated tree peonies (genus
      Paeonia L.) are among the most popular ornamental plants in the world; yet, the
      history of their domestication is still unresolved. Here, we explored whether the
      domestication in China of historically cultivated peonies, that is, the common
      and flare cultivated tree peonies, was a single event or whether independent
      domestications occurred. We used 14 nuclear microsatellite markers and a
      comprehensive set of 553 tree peonies collected across China, including common
      tree peonies, flare tree peonies and the wild species or subspecies that are
      potential contributors to the cultivated tree peonies, that is, Paeonia rockii
      ssp. rockii, P. rockii ssp. atava, P. jishanensis and P. decomposita. Assignment
      methods, a principal component analysis and approximate Bayesian computations
      provided clear evidence for independent domestications of these common tree and
      flare tree peonies from two distinct and allopatric wild species, P. jishanensis
      and P. rockii ssp. atava, respectively. This study provides the first example of
      independent domestications of cultivated trees from distinct species and
      locations. This work also yields crucial insight into the history of
      domestication of one of the most popular woody ornamental plants. The cultivated
      peonies represent an interesting case of parallel and convergent evolution. The
      information obtained in this study will be valuable both for improving current
      tree peony breeding strategies and for understanding the mechanisms of
      domestication, diversification and adaptation in plants.

PMID- 24138196
TI  - Meglumine: A novel and efficient catalyst for one-pot, three-component
      combinatorial synthesis of functionalized 2-amino-4H-pyrans.
AB  - An efficient one-pot synthesis of functionalized 2-amino-4H-pyrans by a meglumine
      catalyzed three-component reaction has been developed. A broad range of
      substrates including aromatic and heteroaromatic aldehydes, isatin derivatives,
      and acenaphthenequinone are condensed with enolizable C-H activated compounds and
      alkylmalonates to give the desired products in high to excellent yields. This
      methodology provides an alternative approach for rapid access to construct a
      diversity-oriented library of 4H-pyrans.

PMID- 24138197
TI  - Making traceability work across the entire food supply chain.
AB  - The Institute of Food Technologists held Traceability Research Summits on July
      14, August 22, and November 1, 2011, to address how to meet the growing
      requirement for agriculture and food traceability. Each meeting had a group of
      about 50 individuals who came from food companies, trade associations, local,
      state, and federal governments, 3rd-party traceability solution providers, not
      for-profit corporations, consultants, and consumer groups. They discussed and
      deliberated the objectives of traceability and the means to develop product
      tracing in the food system. A total of 70 people participated in the 3 summits.
      These individuals were invited to participate in a small workgroup responsible
      for considering the details related to product tracing and presenting draft
      concepts to the larger group on November 1, 2011, in Chicago. During this
      meeting, the larger assembly further refined the concepts and came to an
      agreement on the basic principles and overall design of the desired approach to
      traceability. 

PMID- 24138198
TI  - Simeprevir for the treatment of chronic hepatitis C.
AB  - INTRODUCTION: The addition of protease inhibitors such as telaprevir and
      boceprevir with PEGylated interferon and ribavirin has significantly improved
      cure rates for genotype 1 hepatitis C virus (HCV) infection. Simeprevir (TMC435)
      is a second-generation protease inhibitor that is in development for the
      treatment of genotype 1 HCV infection. AREAS COVERED: The authors present: i) an
      overview of Phases I - III clinical trials of simeprevir for HCV infection based
      on peer-reviewed literature and congress presentations and ii) an evaluation of
      the efficacy and safety of simeprevir in the treatment of HCV infection. EXPERT
      OPINION: Simeprevir is a once-daily oral medication that combined with PEGylated
      interferon and ribavirin appears to be a potent and safe agent to treat genotype
      1 HCV infection for patients who are treatment-naive and prior treatment
      failures. Compared to telaprevir and boceprevir, simeprevir will likely be the
      protease inhibitor of choice for genotype 1 HCV infection based on ease of use,
      lower rates of adverse events, including rash and anemia, and no significant
      reported drug-drug interactions. Associated side effects inherent with interferon
      based regimens may be problematic for patients. As HCV therapies evolve into
      interferon-free regimens, simeprevir may potentially be combined with other oral
      direct-acting agents without interferon to treat HCV infection.

PMID- 24138199
TI  - Characterization of the recombinant Candida albicans beta-1,2-mannosyltransferase
      that initiates the beta-mannosylation of cell wall phosphopeptidomannan.
AB  - The presence of beta-mannosides in their cell walls confers specific features on
      the pathogenic yeasts Candida albicans and Candida glabrata compared with non
      pathogenic yeasts. In the present study, we investigated the enzymatic properties
      of Bmt1 (beta-mannosyltransferase 1), a member of the recently identified beta
      mannosyltransferase family, from C. albicans. A recombinant soluble enzyme
      lacking the N-terminal region was expressed as a secreted protein from the
      methylotrophic yeast Pichia pastoris. In parallel, functionalized natural
      oligosaccharides isolated from Saccharomyces cerevisiae and a C. albicans mutant
      strain, as well as synthetic alpha-oligomannosides, were prepared and used as
      potential acceptor substrates. Bmt1p preferentially utilizes substrates
      containing linear chains of alpha-1,2-linked mannotriose or mannotetraose. The
      recombinant enzyme consecuti-vely transfers two mannosyl units on to these
      acceptors, leading to the production of alpha-mannosidase-resistant
      oligomannosides. NMR experiments further confirmed the presence of a terminal
      betaMan (beta-1,2-linked mannose) unit in the first enzyme product. In the
      future, a better understanding of specific beta-1,2-mannosyltransferase molecular
      requirements will help the design of new potential antifungal drugs. 

PMID- 24138200
TI  - Can we match donors and recipients in a cost-effective way?

PMID- 24138201
TI  - The association of pretransplant ferritin level with waiting list and post
      transplant survival. Does ferritin actually predict outcome?
AB  - Recent data suggest an association of serum ferritin (SF) with waiting list (WL)
      and postliver transplant (LT) outcomes. To assess the predictive capacity of SF
      on pre- and post-LT outcomes, and to identify whether recipient or donor liver
      siderosis is associated with post-LT survival; a retrospective analysis of 1079
      patients assessed for first LT, 2000-2007 was performed. Iron deposition in the
      liver tissue was assessed using a semi-quantitative grading system. Median age
      was 54 (18-82) years and 67% were male. Seventeen per cent had hepatocellular
      carcinoma (HCC). Median Model for End-stage Liver Disease MELD score was 14 (6
      40), ferritin was 174 MUg/l (4-4597) with 36.5% had a SF >= MUg/l. Age (OR =
      1.028) and MELD score (OR = 1.158) were independently associated with WL
      mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR =
      1.542) and cold ischemia time (CIT) >= 10 h (OR = 1.418) were independently
      associated with post-LT survival (P < 0.05). Explant siderosis grade <2 was seen
      in 376 (71.7%) patients. Patients with explant siderosis grade >= 2 had inferior
      12-month post-LT survival (P = 0.030). Presence of graft siderosis (15.8% of
      patients) was not associated with survival. In conclusion, we found a limited
      role for SF as a prognostic indicator for pre- or post-transplant survival.

PMID- 24138202
TI  - Recombinant production of peptide C-terminal alpha-amides using an engineered
      intein.
AB  - Peptides are of increasing interest as therapeutics in a wide range of diseases,
      including metabolic diseases such as diabetes and obesity. In the latter, peptide
      hormones such as peptide YY (PYY) and pancreatic peptide (PP) are important
      templates for drug design. Characteristic for these peptides is that they contain
      a C-terminal that is alpha-amidated, and this amidation is crucial for biological
      function. A challenge is to generate such peptides by recombinant means and
      particularly in a production scale. Here, we have examined an intein-mediated
      approach to generate a PYY derivative in a larger scale. Initially, we
      experienced challenges with hydrolysis of the intein fusion protein, which was
      reduced by a T3C mutation in the intein. Subsequently, we further engineered the
      intein to decrease the absolute size and improve the relative yield of the PYY
      derivative, which was achieved by substituting 54 residues of the 198 amino acid
      intein with an eight amino acid linker. The optimized intein construct was used
      to produce the PYY derivative under high cell density cultivation conditions,
      generating the peptide thioester precursor in good yields and subsequent
      amidation provided the target peptide. 

PMID- 24138203
TI  - Identification and characterization of Cronobacter strains isolated from powdered
      infant foods.
AB  - Cronobacter spp. (formerly Enterobacter sakazakii) is responsible for rare but
      fatal cases of infection in neonates and immunocompromised infants. The aim of
      our study was to characterize Cronobacter strains isolated from powdered infant
      foods in Public Health Authority of the Slovak Republic in 2009-2010. Powdered
      infant food products have been analysed using currently available standard method
      ISO/TS 22964: 2006 for the detection of Cronobacter spp. complemented with qPCR
      confirmation of positive strains. Thirteen Cronobacter strains were isolated from
      more than 900 powdered infant formulae, milk-based and cereal-based powdered
      weaning food products. The strains were assigned to five biogroups and ten
      multilocus sequence typing (MLST) sequence types. In total, twelve strains were
      identified as Cronobacter sakazakii and one strain as Cronobacter dublinensis.
      Multiple strains originated from parallel isolation were obtained in three
      samples and the variability between strains from the same food was observed
      twice. The results are in agreement with the hypothesis that the Cronobacter
      contamination detected in infant powdered food is low and originating in various
      accidental sources. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      characterized Cronobacter strains isolated from powdered infant formulae and
      weaning foods by biotyping and multilocus sequence typing. The later method was
      shown to be more discriminative and suitable for both species identification and
      subtyping. Low level (0.9%) of Cronobacter positivity was observed in 916
      samples. Multiple sequence types were observed among strains isolated from the
      same food product. This highlights that multiple isolates from each single sample
      should be analysed in epidemiological studies, since more than one genetic
      subtype may be present.

PMID- 24138204
TI  - Intraoperative 5-aminolevulinic acid-induced fluorescence in primary central
      nervous system lymphoma.
AB  - The authors report a case of primary CNS lymphoma located in the floor of the
      fourth ventricle that showed intense fluorescence after preoperative
      administration of 5-aminolevulinic acid. The authors believe that this is the
      first demonstration of a 5-aminolevulinic acid-induced fluorescence pattern in
      primary CNS lymphoma. 

PMID- 24138205
TI  - Factors neurosurgery candidates use when choosing a residency program.
AB  - OBJECT: Many factors affect an applicant's decision when selecting a residency
      program. While some issues are likely important to all applicants, others may be
      specific to, or weighed differently by, those applying to certain specialties. In
      an effort to better understand how applicants to neurosurgery programs make
      decisions about relative rank, the authors created a survey to identify the
      program characteristics thought most important by applicants. METHODS: An
      electronic survey was created and posted to the neurosurgery residency
      coordinator's forum. Coordinators throughout the country were asked to send the
      survey link to students who were scheduled to begin as first-year residents in
      July of 2012. A paper copy of the survey was also distributed at the Society of
      Neurological Surgeons intern boot camp in Atlanta, Georgia, in July of 2012.
      RESULTS: One hundred ninety-six students obtained a neurosurgical postgraduate
      year 1 position in the 2011-2012 match; 40 survey responses were received
      (response rate 20.4%). The factors cited as being most important in selecting a
      residency were the residents currently in the program, team camaraderie, and the
      number of operative cases performed. The interview day, specifically the
      opportunity to talk to the residents, was also thought to be important, as was
      the knowledge that the applicant would likely be ranked by the program.
      CONCLUSIONS: Applicants for neurosurgical training choose a program for reasons
      similar to those given by applicants to other specialties. Neurosurgery
      applicants seem marginally more interested in an emphasis on academics and
      research and slightly less concerned with a program's location, but overall, the
      differences appear minimal. The interview process is very important, and contact
      by a representative after the interview also seems significant in applicants'
      decision making. By recognizing what applicants think is important in choosing a
      residency, programs can more effectively recruit residents and more efficiently
      use faculty time and department resources.

PMID- 24138206
TI  - Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify
      residual tumor in glioblastoma surgery.
AB  - OBJECT: The goal of surgery in high-grade gliomas is to maximize the resection of
      contrast-enhancing tumor without causing additional neurological deficits.
      Intraoperative MRI improves surgical results. However, when using contrast
      material intraoperatively, it may be difficult to differentiate between
      surgically induced enhancement and residual tumor. The purpose of this study was
      to assess the usefulness of intraoperative dynamic contrast-enhanced T1-weighted
      MRI to guide this differential diagnosis and test it against tissue
      histopathology. METHODS: Preoperative and intraoperative dynamic contrast
      enhanced MRI was performed in 21 patients with histopathologically confirmed WHO
      Grade IV gliomas using intraoperative 3-T MRI. Standardized regions of interest
      (ROIs) were placed manually at 2 separate contrast-enhancing areas at the
      resection border for each patient. Time-intensity curves (TICs) were generated
      for each ROI. All ROIs were biopsied and the TIC types were compared with
      histopathological results. Pharmacokinetic modeling was performed in the last 10
      patients to confirm nonparametric TIC analysis findings. RESULTS: Of the 42
      manually selected ROIs in 21 patients, 25 (59.5%) contained solid tumor tissue
      and 17 (40.5%) retained the brain parenchymal architecture but contained
      infiltrating tumor cells. Time-intensity curves generated from residual contrast
      enhancing tumor and their preoperative counterparts were comparable and showed a
      quick and persistently increasing slope ("climbing type"). All 17 TICs obtained
      from regions that did not contain solid tumor tissue were undulating and low in
      amplitude, compared with those obtained from residual tumors ("low-amplitude
      type"). Pharmacokinetic findings using the transfer constant, extravascular
      extracellular volume fraction, rate constant, and initial area under the curve
      parameters were significantly different for the tumor mass, nontumoral regions,
      and surgically induced contrast-enhancing areas. CONCLUSIONS: Intraoperative
      dynamic contrast-enhanced MRI provides quick, reproducible, high-quality, and
      simply interpreted dynamic MR images in the intraoperative setting and can aid in
      differentiating surgically induced enhancement from residual tumor.

PMID- 24138207
TI  - Quality of reporting of complex healthcare interventions and applicability of the
      CReDECI list - a survey of publications indexed in PubMed.
AB  - BACKGROUND: The development and evaluation of complex interventions in healthcare
      has obtained increased awareness. The Medical Research Council's (MRC) framework
      for the development and evaluation of complex interventions and its update offers
      guidance for researchers covering the phases development, feasibility/piloting,
      and evaluation. Comprehensive reporting of complex interventions enhances
      transparency and is essential for researchers and policy-makers. Recently, a set
      of 16 criteria for reporting complex interventions in healthcare (CReDECI) was
      published. The aim of this study is to evaluate the reporting quality in
      publications of complex interventions adhering to either the first or the updated
      MRC framework, and to evaluate the applicability of CReDECI. METHODS: A
      systematic PubMed search was conducted. Two reviewers independently checked
      titles and abstracts for inclusion. Trials on complex interventions adhering to
      the MRC framework and including an evaluation study in English and German were
      included. For all included trials and for all publications which reported on
      phases prior to the evaluation study, related publications were identified via
      forward citation tracking. The quality of reporting was assessed independently by
      two reviewers using CReDECI. Inter-rater agreement and time needed to complete
      the assessment were determined. RESULTS: Twenty-six publications on eight trials
      were included. The number of publications per trial ranged from 1 to 6 (mean
      3.25). The trials demonstrate a good reporting quality for the criteria referring
      to the development and feasibility/piloting. For the criteria addressing the
      introduction of the intervention and the evaluation, quality of reporting varied
      widely. Two trials fulfilled 7 and 8 items respectively, five trials fulfilled
      one to five items and one trial offered no information on any item. The mean
      number of items with differing ratings per trial was two. The time needed to rate
      a trial ranged from 30 to 90 minutes, depending on the number of publications.
      CONCLUSIONS: Adherence to the MRC framework seems to have a positive impact on
      the reporting quality on the development and piloting of complex interventions.
      Reporting on the evaluation could be improved. CReDECI is a practical instrument
      to check the reporting quality of complex interventions and could be used
      alongside design-specific reporting guidelines.

PMID- 24138208
TI  - Suicide attempts in major depressed patients with personality disorder.
AB  - Suicide attempters who met criteria for borderline personality disorder (BPD)
      comorbid with major depressive disorder (MDD) were compared to both suicide
      attempters suffering from MDD alone and to attempters with comorbid MDD and other
      personality disorders (PD). Participants were 239 (158 patients with comorbid PD
      and 81 patients with MDD without comorbidity) inpatients consecutively admitted
      after a suicide attempt made in the last 24 hours. Suicide attempters with
      comorbid MDD and BPD had more frequent previous suicide attempts and were more
      likely to have a history of aggressive behaviors and alcohol and drug use
      disorders compared with patients suffering from MDD without Axis II comorbidity. 

PMID- 24138209
TI  - Activation of proteinase-activated receptor 2 prevents apoptosis of lung cancer
      cells.
AB  - The therapeutics of lung cancer (LC) is unsatisfactory. The pathogenesis of LC
      remains unclear. Protease-activated receptors (PAR) are involved in the
      immunoregulation. The present study aims to investigate the activation of PAR2 in
      regulation of the expression of EGFR and apoptosis of LC cells. The results
      showed that exposure to tryptase increased EGFR expression in A549 cells and
      suppressed the cell apoptosis. Tryptase also decreased the expression of Bax and
      increased Bcl-xL levels in A549 cells. We conclude that activation of PAR2 by
      tryptase can decrease the ratio of Bax/Bcl-xL and reduce the LC cell line, A549
      cells, and apoptosis. 

PMID- 24138210
TI  - Effects of age on multidrug resistance protein expression and doxorubicin
      accumulation in cardiac and skeletal muscle.
AB  - 1. Doxorubicin (DOX) is a highly effective and commonly used anthracycline
      antibiotic used to treat cancer patients. The side effects of DOX are manifested
      in a more delayed manner in children and multidrug resistant proteins (MRPs) may
      factor into this phenomenon. MRPs are known to extrude DOX and may factor into
      the degree of cardiac DOX accumulation. 2. The purpose of this study was to
      examine age-related differences in muscle MRP expression and DOX accumulation. 3.
      Female Sprague-Dawley rats were randomly selected to receive a 15-mg DOX/kg body
      weight bolus injection (i.p.) at various ages. 4. Cardiac and extensor digitorum
      longus DOX accumulation was markedly increased as animals aged from 4 to 24
      weeks. In contrast, no differences in soleus accumulation were observed. A
      significant age-related reduction in MRP-2 and MRP-7 expression was detected in
      cardiac and extensor digitorum longus tissues with no age differences in MRP-1
      expression in any tissues analyzed. MRP-6 was not detected in any tissues. 5.
      These data suggest that aging is associated with increased DOX accumulation and
      an age-related decrease in MRP expression may be a factor.

PMID- 24138211
TI  - Evaluation of the antibacterial activity of Piperaceae extracts and nisin on
      Alicyclobacillus acidoterrestris.
AB  - Alicyclobacillus acidoterrestris is a gram-positive aerobic bacterium. This
      bacterium resists pasteurization temperatures and low pH and is usually involved
      in the spoilage of juices and acidic drinks. The objective of this study was to
      evaluate the antibacterial activities of nisin and the species Piper (Piperaceae)
      on A. acidoterrestris. The minimum inhibitory concentration (MIC) and the minimum
      bactericidal concentration (MBC) were determined by the broth microdilution
      method. The species Piper aduncum had the lowest MIC and an MBC of 15.6 MUg/mL
      and was selected for fractionation. Six fractions were obtained, and the
      dichloromethane fraction (F.3) had the lowest MIC/MBC (7.81 MUg/mL). The
      dichloromethane fraction was again fractionized, and a spectral analysis revealed
      that the compound was prenylated chromene (F.3.7). The checkerboard method
      demonstrated that the crude extract (CE) of P. aduncum plus nisin had a
      synergistic interaction (fractional inhibitory concentration [FIC] = 0.24). The
      bactericidal activity of (F.3.7) was confirmed by the time-kill curve. P.
      aduncum, nisin, and prenylated chromene exhibited strong antibacterial activity
      against the spores and vegetative cells of A. acidoterrestris. The results of
      this study suggest that extracts of the genus Piper may provide an alternative to
      the use of thermal processing for controlling A. spoilage. 

PMID- 24138213
TI  - Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's
      complete adjuvant-induced arthritic rats.
AB  - OBJECTIVES: The present study was aimed at investigating the effect of curcumin
      in combination with prednisolone for the effective treatment of arthritis with
      reduced side effects when glucocorticoids therapy is indicated. METHODS:
      Arthritis was induced in wistar rats by subplantar injection of Freund's complete
      adjuvant, and animals were observed for the symptoms of arthritis during the
      period of 21 days. Combined treatment of curcumin with various doses of
      prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the
      efficacy and toxicity induced by steroid. KEY FINDINGS: Arthritic animals showed
      significant increase in tumour necrosis factor-alpha and IL-1beta levels in paw
      tissue and IL-1beta in serum. Combined therapy of curcumin with low doses of
      prednisolone showed pronounced beneficial effect on joint swelling, leucocyte
      count and biochemical parameters compared with prednisolone groups. Among the
      different doses used in the study, prednisolone at 1.25 mg/kg in combination with
      curcumin showed beneficial anti-arthritic activity and also reduced the steroid
      toxicity. This is evidenced by increase in body weight, low toxicity to immune
      organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and
      potent inhibition of cytokines in combination group. CONCLUSION: Therefore,
      combined treatment of curcumin with low doses of prednisolone may find
      therapeutic use in arthritis.

PMID- 24138214
TI  - Mental rotation performance in children with hydrocephalus both with and without
      spina bifida.
AB  - The mental rotation ability in children with hydrocephalus and those with both
      hydrocephalus and spina bifida in comparison to healthy controls was investigated
      in this study. All groups performed a chronometric mental rotation test. Compared
      to children with hydrocephalus, children with both spina bifida and hydrocephalus
      showed an impaired mental rotation performance, demonstrated by slower reaction
      times. No significant performance difference was found between children with
      spina bifida and healthy controls. Error rates were comparable between groups
      indicating that the impaired mental rotation performance in children with both
      spina bifida and hydrocephalus is primarily due to motor impairment. 

PMID- 24138215
TI  - A neurodevelopmental perspective on the acquisition of nonverbal cognitive skills
      in adolescents with fragile X syndrome.
AB  - This longitudinal study was designed to investigate trajectories of nonverbal
      cognitive ability in adolescents with fragile X syndrome with respect to the
      relative influence of fragile X mental retardation protein (FMRP), autism symptom
      severity, and environmental factors on visualization and fluid reasoning
      abilities. Males and females with fragile X syndrome (N = 53; ages 10-16 years)
      were evaluated with the Leiter-R at up to four annual assessments. On average, IQ
      declined with age. FMRP levels predicted change in fluid reasoning, but not in
      visualization. The role of FMRP in the neural development that underlies the
      fragile X syndrome cognitive phenotype is discussed. 

PMID- 24138216
TI  - Gray matter structure and morphosyntax within a spoken narrative in typically
      developing children and children with high functioning autism.
AB  - This study examined the relationship between magnetic resonance imaging (MRI)
      based measures of gray matter structure and morphosyntax production in a spoken
      narrative in 17 typical children (TD) and 11 children with high functioning
      autism (HFA) between 6 and 13 years of age. In the TD group, cortical structure
      was related to narrative performance in the left inferior frontal gyrus (Broca's
      area), the right middle frontal sulcus, and the right inferior temporal sulcus.
      No associations were found in children with HFA. These findings suggest a
      systematic coupling between brain structure and spontaneous language in TD
      children and a disruption of these relationships in children with HFA. 

PMID- 24138217
TI  - Developmental variation in amygdala volumes among children with posttraumatic
      stress.
AB  - This article examined associations between indices of maturation (age and Tanner
      stage) and amygdala volumes in 24 youth (aged 7-14) with posttraumatic stress
      disorder symptoms and a matched control group. Fifteen of the youth with exposure
      to trauma were also re-evaluated one year later. A positive association between
      maturation and right amygdala volumes was observed in the trauma group but not in
      controls. Associations with maturation remained when controlling for a number of
      possible covariates and over time. Developmentally younger youth (Tanner stage 1
      and 2) showed increases and older (Tanner stage 3 and 4) decreases in right
      amygdala volumes. 

PMID- 24138218
TI  - Sex differences in the relationship between children's emotional expression
      discrimination and their developing hemispheric lateralization.
AB  - Strength of lateralization for processing facial emotion becomes more right
      hemisphere lateralized throughout childhood, but sex differences in this
      development are not currently understood. This study examines patterns of
      lateralization for emotion discrimination in 185 6-10-year-olds. Strength of
      right hemisphere lateralization was stronger in the older children, and right
      hemisphere dominance emerged at around age 8. Children who were more strongly
      lateralized performed with greater accuracy on a behavioral test of emotion
      discrimination and this relationship was significant for boys but not girls,
      demonstrating that there is a relationship between lateralization and performance
      (particularly, the discrimination of emotions). 

PMID- 24138219
TI  - Outlier SNP markers reveal fine-scale genetic structuring across European hake
      populations (Merluccius merluccius).
AB  - Shallow population structure is generally reported for most marine fish and
      explained as a consequence of high dispersal, connectivity and large population
      size. Targeted gene analyses and more recently genome-wide studies have
      challenged such view, suggesting that adaptive divergence might occur even when
      neutral markers provide genetic homogeneity across populations. Here, 381 SNPs
      located in transcribed regions were used to assess large- and fine-scale
      population structure in the European hake (Merluccius merluccius), a widely
      distributed demersal species of high priority for the European fishery. Analysis
      of 850 individuals from 19 locations across the entire distribution range showed
      evidence for several outlier loci, with significantly higher resolving power.
      While 299 putatively neutral SNPs confirmed the genetic break between basins
      (F(CT) = 0.016) and weak differentiation within basins, outlier loci revealed a
      dramatic divergence between Atlantic and Mediterranean populations (F(CT) range
      0.275-0.705) and fine-scale significant population structure. Outlier loci
      separated North Sea and Northern Portugal populations from all other Atlantic
      samples and revealed a strong differentiation among Western, Central and Eastern
      Mediterranean geographical samples. Significant correlation of allele frequencies
      at outlier loci with seawater surface temperature and salinity supported the
      hypothesis that populations might be adapted to local conditions. Such evidence
      highlights the importance of integrating information from neutral and adaptive
      evolutionary patterns towards a better assessment of genetic diversity.
      Accordingly, the generated outlier SNP data could be used for tackling illegal
      practices in hake fishing and commercialization as well as to develop explicit
      spatial models for defining management units and stock boundaries.

PMID- 24138221
TI  - The chaperone Hsp90 and PPIases of the cyclophilin and FKBP families facilitate
      membrane translocation of Photorhabdus luminescens ADP-ribosyltransferases.
AB  - TccC3 and TccC5 from Photorhabdus luminescens are ADP-ribosyltransferases, which
      modify actin and Rho GTPases, respectively, thereby inducing polymerization and
      clustering of actin. The bacterial proteins are components of the Photorhabdus
      toxin complexes, consisting of the binding and translocation component TcdA1, a
      proposed linker component TcdB2 and the enzymatic component TccC3/5. While the
      action of the toxins on target proteins is clearly defined, uptake and
      translocation of the toxins into the cytosol of target cells are not well
      understood. Here we show by using pharmacological inhibitors that heat shock
      protein 90 (Hsp90) and peptidyl prolyl cis/trans isomerases (PPIases) including
      cyclophilins and FK506-binding proteins (FKBPs) facilitate the uptake of the ADP
      ribosylating toxins into the host cell cytosol. Inhibition of Hsp90 and/or
      PPIases resulted in decreased intoxication of target cells by Photorhabdus toxin
      complexes determined by cell rounding and reduction of transepithelial electrical
      resistance of cell monolayers. ADP-ribosyltransferase activity of toxins and
      toxin-induced pore formation were notimpaired by the inhibitors of Hsp90 and
      PPIases. The Photorhabdus toxins interacted with Hsp90, FKBP51, Cyp40 and CypA,
      suggesting a role of these host cell factors in translocation and/or refolding of
      the ADP-ribosyltransferases. 

PMID- 24138220
TI  - Is agriculture driving the diversification of the Bemisia tabaci species complex
      (Hemiptera: Sternorrhyncha: Aleyrodidae)?: Dating, diversification and
      biogeographic evidence revealed.
AB  - BACKGROUND: Humans and insect herbivores are competing for the same food crops
      and have been for thousands of years. Despite considerable advances in crop pest
      management, losses due to insects remain considerable. The global homogenisation
      of agriculture has supported the range expansion of numerous insect pests and has
      been driven in part by human-assisted dispersal supported through rapid global
      trade and low-cost air passenger transport. One of these pests, is the whitefly,
      Bemisia tabaci, a cryptic species complex that contains some of the world's most
      damaging pests of agriculture. The complex shows considerable genetic diversity
      and strong phylogeographic relationships. One consequence of the considerable
      impact that members of the B. tabaci complex have on agriculture, is the view
      that human activity, particularly in relation to agricultural practices, such as
      use of insecticides, has driven the diversification found within the species
      complex. This has been particularly so in the case of two members of the complex,
      Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED), which have become
      globally distributed invasive species. An alternative hypothesis is that
      diversification is due to paleogeographic and paleoclimatological changes.
      RESULTS: The idea that human activity is driving speciation within the B. tabaci
      complex has never been tested, but the increased interest in fossil whiteflies
      and the growth in molecular data have enabled us to apply a relaxed molecular
      clock and so estimate divergence dates for the major lineages within the B.
      tabaci species complex. The divergence estimates do not support the view that
      human activity has been a major driver of diversification. CONCLUSIONS: Our
      analysis suggests that the major lineages within the complex arose approximately
      60-30 mya and the highly invasive MED and MEAM1 split from the rest of the
      species complex around 12 mya well before the evolution of Homo sapiens and
      agriculture. Furthermore, the divergence dates coincide with a period of global
      diversification that occurred broadly across the plant and animal kingdoms and
      was most likely associated with major climatic and tectonic events.

PMID- 24138222
TI  - Injectable hydrogel incorporating with nanoyarn for bone regeneration.
AB  - Traditional bone grafting requires an open surgical approach to the graft
      application sites with the attendant complications of a large surgical scar,
      increased pain and a longer post-operative recovery. To overcome these
      limitations, there is a great need for the development of better bone graft
      substitutes. In this study, we developed a novel injectable system which was a
      biomimetic bone substitute consisted of Poly (L-lactide-co-epsilon-caprolactone)
      (P(LLA-CL)) nanoyarns suspended in type I collagen hydrogel (Col). A dynamic
      liquid support system was employed to fabricate continuous P(LLA-CL) nanoyarns.
      The electrospun long nanoyarns were chopped into short nanoyarns before they were
      incorporated into Col. The result of rheological evaluation showed that the
      mechanical property of Col was enhanced after the nanoyarns were incorporated
      into it. The mixture of Col and nanoyarn could be smoothly injected out of 16
      gauge needle. In vitro study showed that human mesenchymal stem cells (hMSCs)
      proliferated well on Col with nanoyarns. Alkaline phosphatase activity and
      osteocalcin expression of hMSCs on hydrogel with nanoyarns were much higher than
      those on control groups. This study highlights the potential of using a novel
      injectable biomimetic scaffold for bone regeneration. 

PMID- 24138223
TI  - Nonverbal accommodation in health care communication.
AB  - This exploratory study examined patterns of nonverbal accommodation within health
      care interactions and investigated the impact of communication skills training
      and gender concordance on nonverbal accommodation behavior. The Nonverbal
      Accommodation Analysis System (NAAS) was used to code the nonverbal behavior of
      physicians and patients within 45 oncology consultations. Cases were then placed
      in one of seven categories based on patterns of accommodation observed across the
      interaction. Results indicated that across all NAAS behavior categories,
      physician-patient interactions were most frequently categorized as joint
      convergence, followed closely by asymmetrical-patient convergence. Among
      paraverbal behaviors, talk time, interruption, and pausing were most frequently
      characterized by joint convergence. Among nonverbal behaviors, eye contact,
      laughing, and gesturing were most frequently categorized as asymmetrical
      physician convergence. Differences were predominantly nonsignificant in terms of
      accommodation behavior between pre- and post-communication skills training
      interactions. Only gesturing proved significant, with post-communication skills
      training interactions more likely to be categorized as joint convergence or
      asymmetrical-physician convergence. No differences in accommodation were noted
      between gender-concordant and nonconcordant interactions. The importance of
      accommodation behavior in health care communication is considered from a patient
      centered care perspective. 

PMID- 24138224
TI  - An update on the pharmacotherapy for endometrial cancer.
AB  - INTRODUCTION: Endometrial cancer (EC) is the seventh most common malignancy in
      women. Most cases have a favorable prognosis because they present an early stage
      disease at diagnosis. Treatment currently comprises surgery with or without
      adjuvant approaches. A combination of radiation therapy, chemotherapy or hormonal
      therapy (HT) is usually administered. This article gives an update concerning the
      role of synthetic drugs in EC, reviewing the most recent data from Phase III
      randomized-controlled trials onwards. AREAS COVERED: Over the years, chemotherapy
      has become the treatment mainstay in both high-risk or locally advanced EC and in
      metastatic or recurrent disease. Carboplatin plus paclitaxel is currently
      considered the standard chemotherapy regimen with a well-tolerated toxicity
      profile. HT is an alternative option in women with advanced EC and important co
      morbidities, and in young women with very early stage disease. EXPERT OPINION:
      Basic results of EC treatment during the last decade were collected. There is a
      need of more advances in treatment. The use of biomarkers, necessary for the
      success of a therapeutic strategy, and the identification of an ad-hoc
      population, are two important goals. In the authors' opinion, the development of
      comprehensive tumor bio-banks and international networks represent the right
      approach to foster translational studies and obtain improvement in patient
      outcomes.

PMID- 24138225
TI  - Shortening the Current Opioid Misuse Measure via computer-based testing: a
      retrospective proof-of-concept study.
AB  - BACKGROUND: The Current Opioid Misuse Measure (COMM) is a self-report
      questionnaire designed to help identify aberrant drug-related behavior in
      respondents who have been prescribed opioids for chronic pain. The full-length
      form of the COMM consists of 17 items. Some individuals, especially compromised
      individuals, may be deterred from taking the full questionnaire due to its
      length. This study examined the use of curtailment and stochastic curtailment,
      two computer-based testing approaches that sequentially determine the test length
      for each individual, to reduce the respondent burden of the COMM without
      compromising sensitivity and specificity. METHODS: Existing data from n = 415
      participants, all of whom had taken the full-length COMM and had been classified
      via the Aberrant Drug Behavior Index (ADBI), were divided into training (n = 214)
      and test (n = 201) sets. Post-hoc analysis of the test set was performed to
      evaluate the screening results and test lengths that would have been obtained, if
      curtailment or stochastic curtailment had been used. Sensitivity, specificity,
      and average test length were calculated for each method and compared with the
      corresponding values of the full-length test. RESULTS: The full-length COMM had a
      sensitivity of 0.703 and a specificity of 0.701 for predicting the ADBI.
      Curtailment reduced the average test length by 22% while maintaining the same
      sensitivity and specificity as the full-length COMM. Stochastic curtailment
      reduced the average test length by as much as 59% while always obtaining a
      sensitivity of at least 0.688 and a specificity of at least 0.701 for predicting
      the ADBI. CONCLUSIONS: Curtailment and stochastic curtailment have the potential
      to achieve substantial reductions in respondent burden without compromising
      sensitivity and specificity. The two sequential methods should be considered for
      future computer-based administrations of the COMM.

PMID- 24138226
TI  - Identification of the novel HLA-A*24:233 allele in a Chinese individual.

PMID- 24138227
TI  - Time scales in the approach to equilibrium of macroscopic quantum systems.
AB  - We prove two theorems concerning the time evolution in general isolated quantum
      systems. The theorems are relevant to the issue of the time scale in the approach
      to equilibrium. The first theorem shows that there can be pathological situations
      in which the relaxation takes an extraordinarily long time, while the second
      theorem shows that one can always choose an equilibrium subspace, the relaxation
      to which requires only a short time for any initial state. 

PMID- 24138228
TI  - Oblique breathers generated by a flow of two-component Bose-Einstein condensates
      past a polarized obstacle.
AB  - We predict that oblique breathers can be generated by a flow of two-component
      Bose-Einstein condensates past a polarized obstacle that attracts one component
      of the condensate and repels the other one. The breather exists if intraspecies
      interaction constants differ from the interspecies interaction constant, and it
      corresponds to the nonlinear excitation of the so-called polarization mode with
      domination of the relative motion of the components. Analytical theory is
      developed for the case of small-amplitude breathers that is in reasonable
      agreement with the numerical results. 

PMID- 24138229
TI  - Simple manipulation of a microwave dressed-state ion qubit.
AB  - Many schemes for implementing quantum information processing require that the
      atomic states used have a nonzero magnetic moment; however, such magnetically
      sensitive states of an atom are vulnerable to decoherence due to fluctuating
      magnetic fields. Dressing an atom with external fields is a powerful method of
      reducing such decoherence [N. Timoney et al., Nature (London) 476, 185 (2011)].
      We introduce an experimentally simpler method of manipulating such a dressed
      state qubit, which allows the implementation of general rotations of the qubit,
      and demonstrate this method using a trapped ytterbium ion.

PMID- 24138231
TI  - Dual lattice simulation of the abelian gauge-Higgs model at finite density: an
      exploratory proof of concept study.
AB  - The U(1) gauge-Higgs model with two flavors of opposite charge and a chemical
      potential is mapped exactly to a dual representation where matter fields
      correspond to loops of flux and the gauge fields are represented by surfaces. The
      complex action problem of the conventional formulation at finite chemical
      potential MU is overcome in the dual representation, and the partition sum has
      only real and nonzero contributions. We simulate the model in the dual
      representation using a generalized worm algorithm, explore the phase diagram, and
      study condensation phenomena at finite MU. 

PMID- 24138230
TI  - Detection of B-mode polarization in the cosmic microwave background with data
      from the South Pole Telescope.
AB  - Gravitational lensing of the cosmic microwave background generates a curl pattern
      in the observed polarization. This "B-mode" signal provides a measure of the
      projected mass distribution over the entire observable Universe and also acts as
      a contaminant for the measurement of primordial gravity-wave signals. In this
      Letter we present the first detection of gravitational lensing B modes, using
      first-season data from the polarization-sensitive receiver on the South Pole
      Telescope (SPTpol). We construct a template for the lensing B-mode signal by
      combining E-mode polarization measured by SPTpol with estimates of the lensing
      potential from a Herschel-SPIRE map of the cosmic infrared background. We compare
      this template to the B modes measured directly by SPTpol, finding a nonzero
      correlation at 7.7sigma significance. The correlation has an amplitude and scale
      dependence consistent with theoretical expectations, is robust with respect to
      analysis choices, and constitutes the first measurement of a powerful
      cosmological observable. 

PMID- 24138233
TI  - Pion electromagnetic form factor at spacelike momenta.
AB  - A novel method is employed to compute the pion electromagnetic form factor,
      F(pi)(Q2), on the entire domain of spacelike momentum transfer using the Dyson
      Schwinger equation (DSE) framework in QCD. The DSE architecture unifies this
      prediction with that of the pion's valence-quark parton distribution amplitude
      (PDA). Using this PDA, the leading-order, leading-twist perturbative QCD result
      for Q2F(pi)(Q2) underestimates the full computation by just 15% on Q2?8 GeV2, in
      stark contrast to the result obtained using the asymptotic PDA. The analysis
      shows that hard contributions to the pion form factor dominate for Q2?8 GeV2,
      but, even so, the magnitude of Q2F(pi)(Q2) reflects the scale of dynamical chiral
      symmetry breaking, a pivotal emergent phenomenon in the standard model.

PMID- 24138234
TI  - Shape and pairing fluctuation effects on neutrinoless double beta decay nuclear
      matrix elements.
AB  - Nuclear matrix elements (NME) for the most promising candidates to detect
      neutrinoless double beta decay have been computed with energy density functional
      methods including deformation and pairing fluctuations explicitly on the same
      footing. The method preserves particle number and angular momentum symmetries and
      can be applied to any decay without additional fine tunings. The finite range
      density dependent Gogny force is used in the calculations. An increase of 10%-40%
      in the NME with respect to the ones found without the inclusion of pairing
      fluctuations is obtained, reducing the predicted half-lives of these isotopes. 

PMID- 24138235
TI  - Quantum metrology with a scanning probe atom interferometer.
AB  - We use a small Bose-Einstein condensate on an atom chip as an interferometric
      scanning probe to map out a microwave field near the chip surface with a few
      micrometers resolution. With the use of entanglement between the atoms, our
      interferometer overcomes the standard quantum limit of interferometry by 4 dB and
      maintains enhanced performance for interrogation times up to 10 ms. This
      corresponds to a microwave magnetic field sensitivity of 77 pT/?Hz in a probe
      volume of 20 MUm(3). Quantum metrology with entangled atoms is useful in
      measurements with high spatial resolution, since the atom number in the probe
      volume is limited by collisional loss. High-resolution measurements of microwave
      near fields, as demonstrated here, are important for the development of
      integrated microwave circuits for quantum information processing and applications
      in communication technology.

PMID- 24138236
TI  - Anomalous ion charge distribution from cluster nanoplasmas.
AB  - In nearly all the intense laser experiments with nanoclusters, the key
      observation has been that immense ionization drives highly charged ions to
      highest energies while low charge ions, if any, have lower kinetic energies. We
      show experimental measurements that are contrary to this established notion. The
      active role of outer-ionized electrons in a multicluster interaction is shown to
      effectively reduce high charge ions to low charge states with no loss of
      momentum. The role of Rydberg excited clusters, intrinsic in dense cluster
      ensembles, is identified and a quantitative analysis is shown to comprehensively
      explain the anomalous charge distribution and ion energies observed in
      experiments. 

PMID- 24138237
TI  - Nuclear polarization corrections to the MU4He+ Lamb shift.
AB  - Stimulated by the proton radius conundrum, measurements of the Lamb shift in
      various light muonic atoms are planned at PSI. The aim is to extract the rms
      charge radius with high precision, limited by the uncertainty in the nuclear
      polarization corrections. We present an ab initio calculation of the nuclear
      polarization for MU(4)He(+) leading to an energy correction in the 2S-2P
      transitions of delta(pol)(A)=-2.47 meV +/-6%. We use two different state-of-the
      art nuclear Hamiltonians and utilize the Lorentz integral transform with
      hyperspherical harmonics expansion as few-body methods. We take into account the
      leading multipole contributions, plus Coulomb, relativistic, and finite-nucleon
      size corrections. Our main source of uncertainty is the nuclear Hamiltonian,
      which currently limits the attainable accuracy. Our predictions considerably
      reduce the uncertainty with respect to previous estimates and should be
      instrumental to the MU(4)He(+) experiment planned for 2013.

PMID- 24138238
TI  - Optical spin squeezing: bright beams as high-flux entangled photon sources.
AB  - In analogy with the spin-squeezing inequality of Wang and Sanders [Phys. Rev. A
      68, 012101 (2003)], we find inequalities describing macroscopic polarization
      correlations that are obeyed by all classical fields and whose violation implies
      entanglement of the photons that make up the optical beam. We consider a
      realistic and exactly solvable experimental scenario employing polarization
      squeezed light from an optical parametric oscillator (OPO) and find polarization
      entanglement for postselected photon pairs separated by less than the OPO
      coherence time. The entanglement is robust against losses and extremely bright:
      efficiency can exceed that of existing "ultrabright" pair sources by at least an
      order of magnitude. This translation of spin-squeezing inequalities to the
      optical domain will enable direct tests of discrete-variable entanglement in a
      squeezed state. 

PMID- 24138239
TI  - Casimir momentum of a chiral molecule in a magnetic field.
AB  - In a classical description, a neutral, polarizable object acquires a kinetic
      momentum when exposed to crossed electric and magnetic fields. In the presence of
      only a magnetic field no such momentum exists classically, although it is
      symmetry allowed for an object lacking mirror symmetry. We perform a full QED
      calculation to show that the quantum vacuum coupled to a chiral molecule provides
      it with a kinetic "Casimir" momentum directed along the magnetic field, and
      proportional to its molecular rotatory power and to the fine structure constant. 

PMID- 24138240
TI  - Chaotic systems with absorption.
AB  - Motivated by applications in optics and acoustics we develop a dynamical-system
      approach to describe absorption in chaotic systems. We introduce an operator
      formalism from which we obtain (i) a general formula for the escape rate kappa in
      terms of the natural conditionally invariant measure of the system, (ii) an
      increased multifractality when compared to the spectrum of dimensions D(q)
      obtained without taking absorption and return times into account, and (iii) a
      generalization of the Kantz-Grassberger formula that expresses D(1) in terms of
      kappa, the positive Lyapunov exponent, the average return time, and a new
      quantity, the reflection rate. Simulations in the cardioid billiard confirm these
      results.

PMID- 24138241
TI  - Slow stochastic switching by collective chaos of fast elements.
AB  - Coupled dynamical systems with one slow element and many fast elements are
      analyzed. By averaging over the dynamics of the fast variables, the adiabatic
      kinetic branch is introduced for the dynamics of the slow variable in the
      adiabatic limit. The dynamics without the limit are found to be represented by
      stochastic switching over these branches mediated by the collective chaos of the
      fast elements, while the switching frequency shows a complicated dependence on
      the ratio of the two time scales with some resonance structure. The ubiquity of
      the phenomena in the slow-fast dynamics is also discussed. 

PMID- 24138242
TI  - Synergetic fluid mixing from viscous fingering and alternating injection.
AB  - We study mixing of two fluids of different viscosity in a microfluidic channel or
      porous medium. We show that the synergetic action of alternating injection and
      viscous fingering leads to a dramatic increase in mixing efficiency at high
      Peclet numbers. Based on observations from high-resolution simulations, we
      develop a theoretical model of mixing efficiency that combines a hyperbolic
      mixing model of the channelized region ahead and a mixing-dissipation model of
      the pseudosteady region behind. Our macroscopic model quantitatively reproduces
      the evolution of the average degree of mixing along the flow direction and can be
      used as a design tool to optimize mixing from viscous fingering in a microfluidic
      channel. 

PMID- 24138243
TI  - Influence of droplet geometry on the coalescence of low viscosity drops.
AB  - The coalescence of water drops on a substrate is studied experimentally. We focus
      on the rapid growth of the bridge connecting the two drops, which very quickly
      after contact ensues from a balance of surface tension and liquid inertia. For
      drops with contact angles below 90 degrees , we find that the bridge grows with a
      self-similar dynamics that is characterized by a height h~t(2/3). By contrast,
      the geometry of coalescence changes dramatically for contact angles at 90 degrees
      , for which we observe h~t(1/2), just as for freely suspended spherical drops in
      the inertial regime. We present a geometric model that quantitatively captures
      the transition from 2/3 to 1/2 exponent, and unifies the inertial coalescence of
      sessile drops and freely suspended drops.

PMID- 24138244
TI  - Axisymmetric turbulent wakes with new nonequilibrium similarity scalings.
AB  - The recently discovered nonequilibrium turbulence dissipation law implies the
      existence of axisymmetric turbulent wake regions where the mean flow velocity
      deficit decays as the inverse of the distance from the wake-generating body and
      the wake width grows as the square root of that distance. This behavior is
      different from any documented boundary-free turbulent shear flow to date. Its
      existence is confirmed in wind tunnel experiments of wakes generated by plates
      with irregular edges placed normal to an incoming free stream. The wake
      characteristics of irregular bodies such as buildings, bridges, mountains, trees,
      coral reefs, and wind turbines are critical in many areas of environmental
      engineering and fluid mechanics. 

PMID- 24138245
TI  - Unraveling quasiperiodic relaxations of transport barriers with gyrokinetic
      simulations of tokamak plasmas.
AB  - The generation and dynamics of transport barriers governed by sheared poloidal
      flows are analyzed in flux-driven 5D gyrokinetic simulations of ion temperature
      gradient driven turbulence in tokamak plasmas. The transport barrier is triggered
      by a vorticity source that polarizes the system. The chosen source captures
      characteristic features of some experimental scenarios, namely, the generation of
      a sheared electric field coupled to anisotropic heating. For sufficiently large
      shearing rates, turbulent transport is suppressed and a transport barrier builds
      up, in agreement with the common understanding of transport barriers. The
      vorticity source also governs a secondary instability--driven by the temperature
      anisotropy (T(?)?T(?)). Turbulence and its associated zonal flows are generated
      in the vicinity of the barrier, destroying the latter due to the screening of the
      polarization source by the zonal flows. These barrier relaxations occur
      quasiperiodically, and generically result from the decoupling between the
      dynamics of the barrier generation, triggered by the source driven sheared flow,
      and that of the crash, triggered by the secondary instability. This result
      underlines that barriers triggered by sheared flows are prone to relaxations
      whenever secondary instabilities come into play.

PMID- 24138246
TI  - Plasma response to a varying degree of stress.
AB  - We report experimental evidence of a seamless transition between three distinct
      modes in a magnetized plasma with a transverse sheared flow as the ratio of the
      ion gyroradius to the shear scale length (a measure of shear magnitude) is
      varied. This was achieved using a dual plasma configuration in a laboratory
      experiment, where a sheared flow oriented perpendicular to a background magnetic
      field is localized at the boundary of the plasmas. This confirms the basic theory
      that plasma is unstable to transverse velocity shear in a broad frequency and
      wavelength range. The experiment characterizes the compression or relaxation of
      boundary layers often generated in a variety of laboratory and space plasma
      processes. 

PMID- 24138247
TI  - Radial localization of toroidicity-induced Alfven eigenmodes.
AB  - Linear gyrokinetic simulation of fusion plasmas finds a radial localization of
      the toroidal Alfven eigenmodes (TAEs) due to the nonperturbative energetic
      particle (EP) contribution. The EP-driven TAE has a radial mode width much
      smaller than that predicted by the magnetohydrodynamic theory. The TAE radial
      position stays around the strongest EP pressure gradients when the EP profile
      evolves. The nonperturbative EP contribution is also the main cause for the
      breaking of the radial symmetry of the ballooning mode structure and for the
      dependence of the TAE frequency on the toroidal mode number. These phenomena are
      beyond the picture of the conventional magnetohydrodynamic theory. 

PMID- 24138248
TI  - Quasiparticle lifetime in ultracold fermionic mixtures with density and mass
      imbalance.
AB  - We show that atomic Fermi mixtures with density and mass imbalance exhibit a rich
      diversity of scaling laws for the quasiparticle decay rate beyond the quadratic
      energy and temperature dependence of conventional Fermi liquids. For certain
      densities and mass ratios, the decay rate is linear, whereas in other cases, it
      exhibits a plateau. Remarkably, this plateau extends from the deeply degenerate
      to the high temperature classical regime of the light species. Many of these
      scaling laws are analogous to what is found in very different systems, including
      dirty metals, liquid metals, and high temperature plasmas. The Fermi mixtures can
      in this sense span a whole range of seemingly diverse and separate physical
      systems. Our results are derived in the weakly interacting limit, making them
      quantitatively reliable. The different regimes can be detected with radio
      frequency spectroscopy. 

PMID- 24138249
TI  - Analytic solution of the approach of quantum vortices towards reconnection.
AB  - Experimental and simulational studies of the dynamics of vortex reconnections in
      quantum fluids showed that the distance d between the reconnecting vortices is
      close to a universal time dependence d=D[kappa|t(0)-t|](alpha) with alpha
      fluctuating around 1/2 and kappa=h/m is the quantum of circulation. Dimensional
      analysis, based on the assumption that the quantum of circulation kappa=h/m is
      the only relevant parameter in the problem, predicts alpha=1/2. The theoretical
      calculation of the dimensionless coefficient D in this formula remained an open
      problem. In this Letter we present an analytic calculation of D in terms of the
      given geometry of the reconnecting vortices. We start from the numerically
      observed generic geometry on the way to vortex reconnection and demonstrate that
      the dynamics is well described by a self-similar analytic solution which provides
      the wanted information.

PMID- 24138250
TI  - Three-dimensional Anderson localization in variable scale disorder.
AB  - We report on the impact of variable-scale disorder on 3D Anderson localization of
      a noninteracting ultracold atomic gas. A spin-polarized gas of fermionic atoms is
      localized by allowing it to expand in an optical speckle potential. Using a
      sudden quench of the localized density distribution, we verify that the density
      profile is representative of the underlying single-particle localized states. The
      geometric mean of the disordering potential correlation lengths is varied by a
      factor of 4 via adjusting the aperture of the speckle focusing lens. We observe
      that the root-mean-square size of the localized gas increases approximately
      linearly with the speckle correlation length, in qualitative agreement with the
      scaling predicted by weak scattering theory. 

PMID- 24138251
TI  - Superconducting vortex lattices for ultracold atoms.
AB  - We propose and analyze a nanoengineered vortex array in a thin-film type-II
      superconductor as a magnetic lattice for ultracold atoms. This proposal addresses
      several of the key questions in the development of atomic quantum simulators. By
      trapping atoms close to the surface, tools of nanofabrication and structuring of
      lattices on the scale of few tens of nanometers become available with a
      corresponding benefit in energy scales and temperature requirements. This can be
      combined with the possibility of magnetic single site addressing and manipulation
      together with a favorable scaling of superconducting surface-induced decoherence.

PMID- 24138232
TI  - Search for the lepton-flavor-violating decays B(s)0->e(+/-)MU(?) and B0->e(+/
      )MU(?).
AB  - A search for the lepton-flavor-violating decays B(s)0->e(+/-)MU(?) and B0->e(+/
      )MU(?) is performed with a data sample, corresponding to an integrated luminosity
      of 1.0 fb(-1) of pp collisions at ?s=7 TeV, collected by the LHCb experiment. The
      observed number of B(s)0->e(+/-)MU(?) and B0->e(+/-)MU(?) candidates is
      consistent with background expectations. Upper limits on the branching fractions
      of both decays are determined to be B(B(s)0->e(+/-)MU(?))<1.1(1.4)*10(-8) and
      B(B0->e(+/-)MU(?))<2.8(3.7)*10(-9) at 90% (95%) confidence level (C.L.). These
      limits are a factor of 20 lower than those set by previous experiments. Lower
      bounds on the Pati-Salam leptoquark masses are also calculated, M(LQ)(B(s)0->e(+/
      )MU(?))>101 TeV/c(2) and M(LQ)(B0->e(+/-)MU(?))>126 TeV/c(2) at 95% C.L., and are
      a factor of 2 higher than the previous bounds.

PMID- 24138252
TI  - Healing of nanocracks by disclinations.
AB  - We present a new mechanism--discovered using molecular dynamics simulations--that
      leads to complete healing of nanocracks. This mechanism relies on the generation
      of crystal defects known as disclinations by migrating grain boundaries. Crack
      healing by disclinations does not require any compressive loads applied normal to
      the crack faces and even occurs under monotonic tensile loading. By closing small
      cracks and suppressing the propagation of others, this mechanism may provide a
      novel way of mitigating internal damage that influences ductility in
      nanocrystalline metals.

PMID- 24138253
TI  - Chemical functionalization of silicene: spontaneous structural transition and
      exotic electronic properties.
AB  - The use of newly discovered silicene for various optoelectronic applications
      depends largely on the possibility of controlling its electronic properties by
      chemical functionalization. To investigate this possibility, we systemically
      study the structural and electronic properties of chemically functionalized
      silicene by employing first-principles calculations combined with the cluster
      expansion approach. Interestingly, we find that chemically functionalized
      epitaxial silicene is generally accompanied by a spontaneous structural
      transition, which originates from the preference of sp(3) hybridization of
      silicon. To realized continuously tunable band gaps, chemical functionalization
      of freestanding silicene at ~900 K is proposed. Finally, we predict that
      metastable silicene can also be used as an important host material to produce
      novel functional materials via substitutional doping. For example, the discovered
      ordered Si(8)P(4) could be a strong candidate for thin-film solar cell absorbers
      beyond bulk Si.

PMID- 24138254
TI  - Nonhysteretic superelasticity of shape memory alloys at the nanoscale.
AB  - We perform molecular dynamics simulations to show that shape memory alloy
      nanoparticles below the critical size not only demonstrate superelasticity but
      also exhibit features such as absence of hysteresis, continuous nonlinear elastic
      distortion, and high blocking force. Atomic level investigations show that this
      nonhysteretic superelasticity results from a continuous transformation from the
      parent phase to martensite under external stress. This aspect of shape memory
      alloys is attributed to a surface effect; i.e., the surface locally retards the
      formation of martensite and then induces a critical-end-point-like behavior when
      the system is below the critical size. Our work potentially broadens the
      application of shape memory alloys to the nanoscale. It also suggests a method to
      achieve nonhysteretic superelasticity in conventional bulk shape memory alloys. 

PMID- 24138255
TI  - Continuum theory of phase separation kinetics for active Brownian particles.
AB  - Active Brownian particles (ABPs), when subject to purely repulsive interactions,
      are known to undergo activity-induced phase separation broadly resembling an
      equilibrium (attraction-induced) gas-liquid coexistence. Here we present an
      accurate continuum theory for the dynamics of phase-separating ABPs, derived by
      direct coarse graining, capturing leading-order density gradient terms alongside
      an effective bulk free energy. Such gradient terms do not obey detailed balance;
      yet we find coarsening dynamics closely resembling that of equilibrium phase
      separation. Our continuum theory is numerically compared to large-scale direct
      simulations of ABPs and accurately accounts for domain growth kinetics, domain
      topologies, and coexistence densities. 

PMID- 24138256
TI  - "Liquid-gas" transition in the supercritical region: fundamental changes in the
      particle dynamics.
AB  - Recently, we have proposed a new dynamic line on the phase diagram in the
      supercritical region, the Frenkel line. Crossing the line corresponds to the
      radical changes of system properties. Here, we focus on the dynamics of model
      Lennard-Jones and soft-sphere fluids. We show that the location of the line can
      be rigorously and quantitatively established on the basis of the velocity
      autocorrelation function (VAF) and mean-square displacements. VAF is oscillatory
      below the line at low temperature, and is monotonically decreasing above the line
      at high temperature. Using this criterion, we show that the crossover of particle
      dynamics and key liquid properties occur on the same line. We also show that
      positive sound dispersion disappears in the vicinity of the line in both systems.
      We further demonstrate that the dynamic line bears no relationship to the
      existence of the critical point. Finally, we find that the region of existence of
      liquidlike dynamics narrows with the increase of the exponent of the repulsive
      part of interatomic potential. 

PMID- 24138257
TI  - Load-induced confinement activates diamond lubrication by water.
AB  - Tribochemical reactions are chemical processes, usually involving lubricant or
      environment molecules, activated at the interface between two solids in relative
      motion. They are difficult to be monitored in situ, which leaves a gap in the
      atomistic understanding required for their control. Here we report the real-time
      atomistic description of the tribochemical reactions occurring at the interface
      between two diamond films in relative motion, by means of large scale ab initio
      molecular dynamics. We show that the load-induced confinement is able to catalyze
      diamond passivation by water dissociative adsorption. Such passivation decreases
      the energy of the contacting surfaces and increases their electronic repulsion.
      At sufficiently high coverages, the latter prevents surface sealing, thus
      lowering friction. Our findings elucidate effects of the nanoscale confinement on
      reaction kinetics and surface thermodynamics, which are important for the design
      of new lubricants.

PMID- 24138258
TI  - Rotational and vibrational excitations of a hydrogen molecule trapped within a
      nanocavity of tunable dimension.
AB  - The rotational and vibrational transitions of a hydrogen molecule weakly adsorbed
      on the Au(110) surface at 10 K were detected by inelastic electron tunneling
      spectroscopy with a scanning tunneling microscope. The energies of the j=0 to j=2
      rotational transition for para-H(2) and HD indicate that the molecule behaves as
      a three-dimensional rigid rotor trapped within the tunnel junction. An increase
      in the bond length of H(2) was precisely measured from the downshift in the
      rotational energy as the tip-substrate distance decreases.

PMID- 24138259
TI  - Exciton-polariton gap solitons in two-dimensional lattices.
AB  - We report on the two-dimensional gap-soliton nature of exciton-polariton
      macroscopic coherent phases (PMCP) in a square lattice with a tunable amplitude.
      The resonantly excited PMCP forms close to the negative mass M point of the
      lattice band structure with energy within the lattice band gap and its wave
      function localized within a few lattice periods. The PMCPs are well described as
      gap solitons resulting from the interplay between repulsive polariton-polariton
      interactions and effective attractive forces due to the negative mass. The
      solitonic nature accounts for the reduction of the PMCP coherence length and
      optical excitation threshold with increasing lattice amplitude. 

PMID- 24138260
TI  - Conductivity of graphene with resonant and nonresonant adsorbates.
AB  - We propose a unified description of transport in graphene with adsorbates that
      fully takes into account localization effects and loss of electronic coherence
      due to inelastic processes. We focus in particular on the role of the scattering
      properties of the adsorbates and analyze in detail cases with resonant or
      nonresonant scattering. For both models, we identify several regimes of
      conduction, depending on the value of the Fermi energy. Sufficiently far from the
      Dirac energy and at sufficiently small concentrations, the semiclassical theory
      can be a good approximation. Near the Dirac energy, we identify different quantum
      regimes, where the conductivity presents universal behaviors. 

PMID- 24138261
TI  - Fundamental differences between quantum spin Hall edge states at zigzag and
      armchair terminations of honeycomb and ruby nets.
AB  - Combining an analytical and numerical approach we investigate the dispersion of
      the topologically protected spin-filtered edge states of the quantum spin Hall
      state on honeycomb and ruby nets with zigzag (ZZ) and armchair (AC) edges. We
      show that the Fermi velocity of the helical edge states on ZZ edges increases
      linearly with the strength of the spin-orbit coupling (SOC) whereas for AC edges
      the Fermi velocity is independent of the SOC. Also the decay length of edge
      states into the bulk is dramatically different for AC and ZZ edges, displaying an
      inverse functional dependence on the SOC. 

PMID- 24138262
TI  - Quantum transport in magnetic topological insulator thin films.
AB  - The experimental observation of the long-sought quantum anomalous Hall effect was
      recently reported in magnetically doped topological insulator thin films [Chang
      et al., Science 340, 167 (2013)]. An intriguing observation is a rapid decrease
      from the quantized plateau in the Hall conductance, accompanied by a peak in the
      longitudinal conductance as a function of the gate voltage. Here, we present a
      quantum transport theory with an effective model for magnetic topological
      insulator thin films. The good agreement between theory and experiment reveals
      that the measured transport originates from a topologically nontrivial conduction
      band which, near its band edge, has concentrated Berry curvature and a local
      maximum in group velocity. The indispensable roles of the broken structure
      inversion and particle-hole symmetries are also revealed. The results are
      instructive for future experiments and transport studies based on first
      principles calculations.

PMID- 24138263
TI  - Engineering topological surface states: HgS, HgSe, and HgTe.
AB  - Using density functional electronic structure calculations, we establish the
      consequences of surface termination and modification on protected surface states
      of metacinnabar (beta-HgS). Whereas we find that the Dirac cone is isotropic and
      well separated from the valence band for the (110) surface, it is highly
      anisotropic at the pure (001) surface. We demonstrate that the anisotropy is
      modified by surface passivation because the topological surface states include
      contributions from dangling bonds. Such dangling bonds exist on all pure surfaces
      within the whole class HgX with X=S, Se, or Te and directly affect the properties
      of the Dirac cone. Surface modifications also alter the spatial location (depth
      and decay length) of the topologically protected edge states, which renders them
      essential for the interpretation of photoemission data. 

PMID- 24138264
TI  - Competing crystal phases in the lowest Landau level.
AB  - We show that the solid phase between the 1/5 and 2/9 fractional quantum Hall
      states arises from an extremely delicate interplay between type-1 and type-2
      composite fermion crystals, clearly demonstrating its nontrivial, strongly
      correlated character. We also compute the phase diagram of various crystals
      occurring over a wide range of filling factors and demonstrate that the elastic
      constants exhibit nonmonotonic behavior as a function of the filling factor,
      possibly leading to distinctive experimental signatures that can help mark the
      phase boundaries separating different kinds of crystals. 

PMID- 24138265
TI  - Excitation of single quasiparticles in a small superconducting Al island
      connected to normal-metal leads by tunnel junctions.
AB  - We investigate the dynamics of individual quasiparticle excitations on a small
      superconducting aluminum island connected to normal metallic leads by tunnel
      junctions. We find the island to be free of excitations within the measurement
      resolution. This allows us to show that the residual heating, which typically
      limits experiments on superconductors, has an ultralow value of less than 0.1 aW.
      By injecting electrons with a periodic gate voltage, we probe electron-phonon
      interaction and relaxation down to a single quasiparticle excitation pair, with a
      measured recombination rate of 16 kHz. Our experiment yields a strong test of BCS
      theory in aluminum as the results are consistent with it without free parameters.

PMID- 24138266
TI  - Chiral edge states and fractional charge separation in a system of interacting
      bosons on a kagome lattice.
AB  - We consider the extended hard-core Bose-Hubbard model on a kagome lattice with
      boundary conditions on two edges. We find that the sharp edges lift the
      degeneracy and freeze the system into a striped order at 1/3 and 2/3 filling for
      zero hopping. At small hopping strengths, holes spontaneously appear and separate
      into fractional charges which move to the edges of the system. This leads to a
      novel edge liquid phase, which is characterized by fractional charges near the
      edges and a finite edge compressibility but no superfluid density. The
      compressibility is due to excitations on the edge which display a chiral symmetry
      breaking that is reminiscent of the quantum Hall effect and topological
      insulators. Large scale Monte Carlo simulations confirm the analytical
      considerations.

PMID- 24138267
TI  - Interplay between classical magnetic moments and superconductivity in quantum one
      dimensional conductors: toward a self-sustained topological Majorana phase.
AB  - We study a one-dimensional interacting electronic liquid coupled to a 1D array of
      classical magnetic moments and to a superconductor. We show that at low energy
      and temperature the magnetic moments and the electrons become strongly entangled
      and that a magnetic spiral structure emerges. For strong enough coupling between
      the electrons and magnetic moments, the 1D electronic liquid is driven into a
      topological superconducting phase supporting Majorana fermions without any fine
      tuning of external parameters. Our analysis applies at low enough temperature to
      a quantum wire in proximity to a superconductor when the hyperfine interaction
      between electrons and nuclear spins is taken into account, or to a chain of
      magnetic adatoms adsorbed on a superconducting surface. 

PMID- 24138268
TI  - Local spin relaxation within the random Heisenberg chain.
AB  - Finite-temperature local dynamical spin correlations S(nn)(omega) are studied
      numerically within the random spin-1/2 antiferromagnetic Heisenberg chain. The
      aim is to explain measured NMR spin-lattice relaxation times in
      BaCu(2)(Si(0.5)Ge(0.5))(2)O(7), which is the realization of a random spin chain.
      In agreement with experiments we find that the distribution of relaxation times
      within the model shows a very large span similar to the stretched-exponential
      form. The distribution is strongly reduced with increasing T, but stays finite
      also in the high-T limit. Anomalous dynamical correlations can be associated with
      the random singlet concept but not directly with static quantities. Our results
      also reveal the crucial role of the spin anisotropy (interaction), since the
      behavior is in contrast with the ones for the XX model, where we do not find any
      significant T dependence of the distribution.

PMID- 24138269
TI  - Charge ordering in a pure spin model: dipolar spin ice.
AB  - We study the dipolar spin-ice model at fixed density of single excitations, rho,
      using a Monte Carlo algorithm where processes of creation and annihilation of
      such excitations are banned. In the limit of rho going to zero, this model
      coincides with the usual dipolar spin-ice model at low temperatures, with the
      additional advantage that a negligible number of monopoles allows for
      equilibration even at the lowest temperatures. Thus, the transition to the
      ordered fundamental state found by Melko, den Hertog, and Gingras in 2001 is
      reached using simple local spin flip dynamics. As the density is increased, the
      monopolar nature of the excitations becomes apparent: the system shows a rich rho
      vs T phase diagram with "charge" ordering transitions analogous to that observed
      for Coulomb charges in lattices. A further layer of complexity is revealed by the
      existence of order both within the charges and their associated vacuum, which can
      only be described in terms of spins--the true microscopic degrees of freedom of
      the system.

PMID- 24138270
TI  - Probing real-space and time-resolved correlation functions with many-body Ramsey
      interferometry.
AB  - We propose to use Ramsey interferometry and single-site addressability, available
      in synthetic matter such as cold atoms or trapped ions, to measure real-space and
      time-resolved spin correlation functions. These correlation functions directly
      probe the excitations of the system, which makes it possible to characterize the
      underlying many-body states. Moreover, they contain valuable information about
      phase transitions where they exhibit scale invariance. We also discuss
      experimental imperfections and show that a spin-echo protocol can be used to
      cancel slow fluctuations in the magnetic field. We explicitly consider examples
      of the two-dimensional, antiferromagnetic Heisenberg model and the one
      dimensional, long-range transverse field Ising model to illustrate the technique.

PMID- 24138271
TI  - Metamaterial transparency induced by cooperative electromagnetic interactions.
AB  - We propose a cooperative asymmetry-induced transparency, CAIT, formed by
      collective excitations in metamaterial arrays of discrete resonators. CAIT can
      display a sharp transmission resonance even when the constituent resonators
      individually exhibit broad resonances. We further show how dynamically
      reconfiguring the metamaterial allows one to actively control the transparency.
      While reminiscent of electromagnetically induced transparency, which can be
      described by independent emitters, CAIT relies on a cooperative response
      resulting from strong radiative couplings between the resonators. 

PMID- 24138272
TI  - Geometrical frustration in amorphous and partially crystallized packings of
      spheres.
AB  - We study the persistence of a geometrically frustrated local order inside
      partially crystallized packings of equal-sized spheres. Measurements by x-ray
      tomography reveal previously unseen grain scale rearrangements occurring inside
      large three-dimensional packings as they crystallize. Three successive structural
      transitions are detected by a statistical description of the local volume
      fluctuations. These compaction regimes are related to the disappearance of
      densely packed tetrahedral patterns of beads. Amorphous packings of monodisperse
      spheres are saturated with these tetrahedral clusters at Bernal's limiting
      density (phi~64%). But, no periodic lattice can be built upon these patterns;
      they are geometrically frustrated and are thus condemned to vanish while the
      crystallization occurs. Remarkably, crystallization-induced grain rearrangements
      can be interpreted in terms of the evolution of key topological features of these
      aggregates.

PMID- 24138273
TI  - Lamellar and inverse micellar structures of skin lipids: effect of templating.
AB  - The outermost layer of skin comprises rigid nonviable cells (corneocytes) in a
      layered lipid matrix. Using atomistic simulations we find that the equilibrium
      phase of the skin lipids is inverse micellar. A model of the corneocyte is used
      to demonstrate that lamellar layering is induced by the patterned corneocyte
      wall. The inverse micellar phase is consistent with in vivo observations in
      regions where corneocyte walls are well separated (lacunar spaces) and in the
      inner layers of skin, and suggests a functional role in the lipid synthesis
      pathway in vivo.

PMID- 24138274
TI  - Coexistence and transition between shear zones in slow granular flows.
AB  - We report experiments on slow granular flows in a split-bottom Couette cell that
      show novel strain localization features. Nontrivial flow profiles have been
      observed which are shown to be the consequence of simultaneous formation of shear
      zones in the bulk and at the boundaries. The fluctuating band model based on a
      minimization principle can be fitted to the experiments over a large variation of
      morphology and filling height with one single fit parameter, the relative
      friction coefficient MU(rel) between wall and bulk. The possibility of multiple
      shear zone formation is controlled by MU(rel). Moreover, we observe that the
      symmetry of an initial state, with coexisting shear zones at both side walls,
      breaks spontaneously below a threshold value of the shear velocity. A dynamical
      transition between two asymmetric flow states happens over a characteristic time
      scale which depends on the shear strength.

PMID- 24138275
TI  - Comment on "Evidence of a cascade and dissipation of solar-wind turbulence at the
      electron gyroscale".

PMID- 24138276
TI  - Sahraoui et al. reply.

PMID- 24138277
TI  - Comment on "Atomistic picture of charge density wave formation at surfaces".

PMID- 24138278
TI  - Frigge et al. reply.

PMID- 24138279
TI  - Comment on "Physical origin and generic control of magnonic band gaps of dipole
      exchange spin waves in width-modulated nanostrip waveguides".

PMID- 24138280
TI  - Lee, Han, and Kim reply.

PMID- 24138281
TI  - Regional thalamic neuropathology in patients with hippocampal sclerosis and
      epilepsy: a postmortem study.
AB  - PURPOSE: Clinical, experimental, and neuroimaging data all indicate that the
      thalamus is involved in the network of changes associated with temporal lobe
      epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with
      potential roles in seizure initiation and propagation. Pathologic changes in the
      thalamus may be a result of an initial insult, ongoing seizures, or retrograde
      degeneration through reciprocal connections between thalamic and limbic regions.
      Our aim was to carry out a neuropathologic analysis of the thalamus in a
      postmortem (PM) epilepsy series, to assess the distribution, severity, and nature
      of pathologic changes and its association with HS. METHODS: Twenty-four epilepsy
      PM cases (age range 25-87 years) and eight controls (age range 38-85 years) were
      studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4
      cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the
      thalamus were stained with cresyl violet (CV), and for glial firbillary acidic
      protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs)
      or field fraction staining values (GFAP, synaptophysin) were measured in four
      thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD),
      mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were
      compared within and between cases. KEY FINDINGS: The severity, nature, and
      distribution of thalamic pathology varied between cases. A pattern that emerged
      was a preferential involvement of the MD in UHS cases with a reduction in mean ND
      ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction
      values for GFAP and lower values for synaptophysin and ND were seen in the
      majority of cases in the MD ipsilateral to the side of sclerosis compared to
      other thalamic nuclei. In addition, differences in the mean ND between classical
      HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05),
      with lower values observed in HS. SIGNIFICANCE: Our study demonstrates that
      stereotypical pathologic changes, as seen in HS, are not clearly defined in the
      thalamus. This may be partly explained by the heterogeneity of our PM study
      group. With quantitation, there is some evidence for preferential involvement of
      the MD, suggesting a potential role in TLE, which requires further investigation.

PMID- 24138282
TI  - Pharmacovigilance in hospice/palliative care: net effect of haloperidol for
      delirium.
AB  - INTRODUCTION: Prescribing practice in hospice/palliative care is largely
      extrapolated from other areas of clinical practice, with few studies of net
      medication effects (benefits and harms) in hospice/palliative care to guide
      prescribing decisions. Hospice/palliative care patients differ in multiple ways
      from better studied participant groups, hence the applicability of studies in
      other participant groups is uncertain. Haloperidol, a butyrophenone derivative
      and dopamine antagonist, is commonly prescribed for nausea, vomiting, and
      delirium in hospice/palliative care. Its frequent use in delirium occurs despite
      little evidence of the effect of antipsychotics on the untreated course of
      delirium. The aim of this study was to examine the immediate and short-term
      clinical benefits and harms of haloperidol for delirium in hospice/palliative
      care patients. METHOD: A consecutive cohort of participants from 14 centers
      across four countries who had haloperidol commenced for delirium were recruited.
      Data were collected at three time points: baseline, 48 hours (clinical benefits),
      and day 10 (clinical harms). Investigators were also able to report clinical
      harms at any time up to 14 days after it was commenced. RESULTS: Of the 119
      participants included, the average dose was 2.1 mg per 24 hours; 42 of 106
      (35.2%) reported benefit at 48 hours. Harm was reported in 14 of 119 (12%) at 10
      days, the most frequent being somnolence (n=11) and urinary retention (n=6).
      Seven participants had their medication ceased due to harms (2 for somnolence and
      2 for rigidity). Approximately half (55/119) were still being treated with
      haloperidol after 10 days. CONCLUSION: Overall, 1 in 3 participants gained net
      clinical benefit at 10 days.

PMID- 24138283
TI  - Identification and expression profiling of Vigna mungo microRNAs from leaf small
      RNA transcriptome by deep sequencing.
AB  - MicroRNAs (miRNAs) represent a class of small non-coding RNA molecules that play
      a crucial role in post-transcriptional gene regulation. Several conserved and
      species-specific miRNAs have been characterized to date, predominantly from the
      plant species whose genome is well characterized. However, information on the
      variability of these regulatory RNAs in economically important but genetically
      less characterized crop species are limited. Vigna mungo is an important grain
      legume, which is grown primarily for its protein-rich edible seeds. miRNAs from
      this species have not been identified to date due to lack of genome sequence
      information. To identify miRNAs from V. mungo, a small RNA library was
      constructed from young leaves. High-throughput Illumina sequencing technology and
      bioinformatic analysis of the small RNA reads led to the identification of 66
      miRNA loci represented by 45 conserved miRNAs belonging to 19 families and eight
      non-conserved miRNAs belonging to seven families. Besides, 13 novel miRNA
      candidates in V. mungo were also identified. Expression patterns of selected
      conserved, non-conserved, and novel miRNA candidates have been demonstrated in
      leaf, stem, and root tissues by quantitative polymerase chain reaction, and
      potential target genes were predicted for most of the conserved miRNAs. This
      information offers genomic resources for better understanding of miRNA mediated
      post-transcriptional gene regulation. 

PMID- 24138285
TI  - Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis and
      management.
AB  - BACKGROUND: Angiodysplasia (AD) of the gastrointestinal (GI) tract is an
      important condition that can cause significant morbidity and -rarely - mortality.
      AIM: To provide an up-to-date comprehensive summary of the literature evaluating
      this disease entity with a particular focus on pathogenesis as well as current
      and emerging diagnostic and therapeutic modalities. Recommendations for treatment
      will be made on the basis of the current available evidence and consensus opinion
      of the authors. METHODS: A systematic literature search was performed. The search
      strategy used the keywords 'angiodysplasia' or 'arteriovenous malformation' or
      'angioectasia' or 'vascular ectasia' or 'vascular lesions' or 'vascular
      abnormalities' or 'vascular malformations' in the title or abstract. RESULTS:
      Most AD lesions (54-81.9%) are detected in the caecum and ascending colon. They
      may develop secondary to chronic low-grade intermittent obstruction of submucosal
      veins coupled with increased vascular endothelial growth factor-dependent
      proliferation. Endotherapy with argon plasma coagulation resolves bleeding in 85%
      of patients with colonic AD. In patients who fail (or are not suitable for) other
      interventions, treatment with thalidomide or octreotide can lead to a clinically
      meaningful response in 71.4% and 77% of patients respectively. CONCLUSIONS:
      Angiodysplasia is a rare, but important, cause of both overt and occult GI
      bleeding especially in the older patients. Advances in endoscopic imaging and
      therapeutic techniques have led to improved outcomes in these patients. The
      choice of treatment should be decided on a patient-by-patient basis. Further
      research is required to better understand the pathogenesis and identify potential
      therapeutic targets.

PMID- 24138286
TI  - Framing medical tourism: an analysis of persuasive appeals, risks and benefits,
      and new media features of medical tourism broker websites.
AB  - This study explores the benefits and risks featured in medical tourism broker
      websites, as well as the types of persuasive appeals that these websites use to
      attract potential customers, from a framing theory perspective. In addition, it
      examines relationships among types of appeals and specific types of health
      related services offered by medical facilities abroad and the role of new media
      modalities within medical tourism broker sites. A content analysis of 91 medical
      tourism broker websites was conducted. The results indicate that the websites
      highly emphasized benefits while downplaying the risks. Specifically, despite
      offering consumers complicated and risky medical procedures, the websites failed
      to report any procedural, postoperative, or legal concerns associated with them.
      Moreover, the results indicated that the websites relied on heavy use of new
      media features to enhance the appeal of the medical services that were offered.
      The implications of these findings, future directions for research, and
      limitations of the study are discussed.

PMID- 24138284
TI  - Hepatitis C virus translation inhibitors targeting the internal ribosomal entry
      site.
AB  - The internal ribosome entry site (IRES) in the 5' untranslated region (UTR) of
      the hepatitis C virus (HCV) genome initiates translation of the viral polyprotein
      precursor. The unique structure and high sequence conservation of the 5' UTR
      render the IRES RNA a potential target for the development of selective viral
      translation inhibitors. Here, we provide an overview of approaches to block HCV
      IRES function by nucleic acid, peptide, and small molecule ligands. Emphasis will
      be given to the IRES subdomain IIa, which currently is the most advanced target
      for small molecule inhibitors of HCV translation. The subdomain IIa behaves as an
      RNA conformational switch. Selective ligands act as translation inhibitors by
      locking the conformation of the RNA switch. We review synthetic procedures for
      inhibitors as well as structural and functional studies of the subdomain IIa
      target and its ligand complexes. 

PMID- 24138287
TI  - Caffeic acid induces keratinocyte differentiation by activation of PPAR-alpha.
AB  - OBJECTIVES: Peroxisome proliferator-activated receptors (PPAR)-alpha plays an
      important role in epidermal differentiation and barrier recovery, and topical
      treatment with PPAR-alpha agonists restores epidermal homeostasis in essential
      fatty acid deficiency and permeability barrier in skin disruptions. Therefore, we
      performed structure-based pharmacophore screening to search for a novel PPAR
      alpha agonist. Caffeic acid was ultimately selected and evaluated for its effects
      on keratinocyte differentiation and epidermal permeability barrier. METHODS: The
      transactivation activity of PPAR-responsive element (PPRE) and cornified envelope
      (CE) formation were assayed. Also, immunoblot analysis and anti-oxidant activity
      were investigated on caffeic acid. KEY FINDINGS: Caffeic acid increases the
      transactivation activity of PPRE and CE formation in keratinocytes. In addition,
      caffeic acid promotes the expression of genes and proteins related to CE
      formation such as involucrin and transglutaminase-1. Additionally, anti-oxidant
      activity were improved by caffeic acid. CONCLUSIONS: Caffeic acid can promote
      keratinocyte differentiation and restore skin barrier homeostasis and is
      suggested to be an appropriate skin therapeutic agent for improving epidermal
      permeability barrier function.

PMID- 24138288
TI  - Psychophysiology of prospective memory.
AB  - Prospective memory involves the self-initiated retrieval of an intention upon an
      appropriate retrieval cue. Cue identification can be considered as an orienting
      reaction and may thus trigger a psychophysiological response. Here we present two
      experiments in which skin conductance responses (SCRs) elicited by prospective
      memory cues were compared to SCRs elicited by aversive stimuli to test whether a
      single prospective memory cue triggers a similar SCR as an aversive stimulus. In
      Experiment 2 we also assessed whether cue specificity had a differential
      influence on prospective memory performance and on SCRs. We found that detecting
      a single prospective memory cue is as likely to elicit a SCR as an aversive
      stimulus. Missed prospective memory cues also elicited SCRs. On a behavioural
      level, specific intentions led to better prospective memory performance. However,
      on a psychophysiological level specificity had no influence. More generally, the
      results indicate reliable SCRs for prospective memory cues and point to
      psychophysiological measures as valuable approach, which offers a new way to
      study one-off prospective memory tasks. Moreover, the findings are consistent
      with a theory that posits multiple prospective memory retrieval stages.

PMID- 24138289
TI  - Comparison between Gleason score and apparent diffusion coefficient obtained from
      diffusion-weighted imaging of prostate cancer patients.
AB  - OBJECTIVES: To correlate the apparent diffusion coefficient (ADC) of prostate
      cancer patients with pathological Gleason scores (GS). METHODS: 40 patients with
      GS 2 + 3, 3 + 3, 3 + 4, or 4 + 4 were selected. The magnetic resonance imaging
      (MRI) study was performed adding axial diffusion-weighted imaging (DWI) sequences
      to the standard MRI protocol. ADC values obtained were correlated with the GS
      data. RESULTS: Statistically significant differences of ADC (p < .05) were found
      among GS groups with a trend of decreasing ADC values with increasing GS.
      CONCLUSIONS: The ADC values may help clinicians to delineate prostate carcinoma,
      recognizing its high- or low-grade compartments.

PMID- 24138290
TI  - Fungal genomes mining to discover novel sterol esterases and lipases as
      catalysts.
AB  - BACKGROUND: Sterol esterases and lipases are enzymes able to efficiently catalyze
      synthesis and hydrolysis reactions of both sterol esters and triglycerides and
      due to their versatility could be widely used in different industrial
      applications. Lipases with this ability have been reported in the yeast Candida
      rugosa that secretes several extracellular enzymes with a high level of sequence
      identity, although different substrate specificity. This versatility has also
      been found in the sterol esterases from the ascomycetes Ophiostoma piceae and
      Melanocarpus albomyces. RESULTS: In this work we present an in silico search of
      new sterol esterase and lipase sequences from the genomes of environmental fungi.
      The strategy followed included identification and search of conserved domains
      from these versatile enzymes, phylogenetic studies, sequence analysis and 3D
      modeling of the selected candidates. CONCLUSIONS: Six potential putative enzymes
      were selected and their kinetic properties and substrate selectivity are
      discussed on the basis of their similarity with previously characterized sterol
      esterases/lipases with known structures.

PMID- 24138291
TI  - Factors influencing long-term outcome after kidney transplantation.
AB  - Many factors influence the long-term outcome of kidney transplantation, which is
      defined very schematically by patient death or renal dysfunction leading to graft
      loss. The most important of these factors is most likely the quality of the
      transplant itself, with kidneys from living donors showing a positive impact,
      while kidneys from expanded criteria donors show deleterious impacts. Various
      clinicopathological scores exist to predict mid- to long-term outcomes and avoid
      the transplantation of kidneys displaying inferior results. The key factors
      related to the recipient include their age as well as disease recurrence, HLA
      matching, HLA immunization, ethnic background, time on dialysis, and
      cardiovascular comorbidities. Renal function, defined based on estimated GFR
      and/or proteinuria values, is a result of all these factors. Delayed graft
      function has a detrimental long-term impact, as does the level of renal function
      impairment either in stable condition or in case of progressing dysfunction.
      Finally, although current immunosuppression regimes are highly efficient in
      preventing acute rejection, the burden of specific (diabetes, nephrotoxicity) and
      nonspecific (infection and cancer) side effects has significant negative long
      term consequences that may well be worse in the future because of the increasing
      ages of both donors and recipients. The development of safer immunosuppression
      strategies is therefore crucial to improve long-term outcomes. 

PMID- 24138292
TI  - Protecting an endangered species: the contribution and constraints of nurses
      working in a specialist role.
AB  - AIM: The project aims to assess current specialist practice in relation to the
      new and ever-changing healthcare climate and explore some of the issues that
      specialist nurses encounter. BACKGROUND: The current financial recession is
      driving a range of economic policy changes and consequently service provision, in
      particular the work and impact of nurses working in a specialist role, being
      examined. This has resulted in many specialist nurses feeling very vulnerable.
      METHOD: A cross sectional survey was completed by nurses working in specialist
      roles (n = 96) in a large health and social care setting in the United Kingdom.
      FINDINGS: A response rate of 62% was achieved: 44% provide nurse led clinics and
      42% are nurse prescribers. The mean length of time qualified as a registered
      nurse was 27 years. Less than a third felt that the current computer system for
      activity recording reflected their current workload and 65% needed administrative
      support. CONCLUSION: This study demonstrates the insufficient resources available
      to specialist nurses resulting in inappropriate but necessary, use of time and
      restricted opportunities for learning and development.

PMID- 24138293
TI  - Metabolic changes during the pu-erh tea pile-fermentation revealed by a liquid
      chromatography tandem mass-spectrometry-based metabolomics approach.
AB  - In the current study, liquid chromatography-mass spectrometry combined with
      multivariate statistical analyses was employed to investigate the time-varying
      biochemical changes during the pile-fermentation process with the emphasis on the
      active ingredients to clarify the manufacturing process of ripened pu-erh tea as
      a whole. The metabolite profiles of different manufacturing processes were unique
      and could be distinguished with the aid of principal component analysis.
      Furthermore, partial least-squares discriminant analysis revealed a pairwise
      discrimination between the raw material group and pile-fermentation process
      groups or the final product group, and 48 differential metabolites with variable
      importance in the projection value greater than 1 were identified, which was
      confirmed by the subsequent hierarchical cluster analysis. These results
      highlight our current understanding of the exact changing process of the
      bioactive compounds during the pile fermentation, and the global change of these
      bioactive compounds provides the special flavor, taste, and health promoting
      effects of ripened pu-erh tea. 

PMID- 24138294
TI  - First-principles predictions of the structure, stability, and photocatalytic
      potential of Cu2O surfaces.
AB  - For a photocatalytic reaction to be thermodynamically allowed, a semiconductor's
      band edges need to be placed appropriately relative to the reaction redox
      potentials. We apply a recently developed scheme for calculating band edges with
      density functional theory (DFT)-based methods to Cu2O, evaluating its available
      thermodynamic overpotential for redox reactions such as water splitting and
      conversion of CO2 to methanol. Because these calculations are surface dependent,
      we first study the low-index surfaces of Cu2O using periodic DFT+U theory to
      characterize and identify the most stable surface, which will be the most
      catalytically relevant. We employ various techniques to calculate the surface
      energy, including the method of "ab initio atomistic thermodynamics". The
      Cu2O(111) surface with (1 * 1) periodicity and surface copper vacancies is
      identified as the most stable at all oxygen partial pressures, although the ideal
      stoichiometric Cu2O(111) surface is relatively close in energy under oxygen-poor
      conditions. These surfaces are then used to calculate the band edges. Comparison
      of the band edges to redox potentials reveals that Cu2O is thermodynamically
      capable of photocatalytic reduction of CO2 to methanol and the reduction and
      oxidation of water. 

PMID- 24138295
TI  - Eosinophilic colitis is a sporadic self-limited disease of middle-aged people: a
      population-based study.
AB  - AIM: Eosinophilic colitis (EC) is a rare manifestation of eosinophilic
      gastrointestinal disorders. Due to its rarity, little information is available on
      its natural history. METHOD: From the single population-based pathology database
      of the Calgary Health Region (comprising a population of 1.28 million in 2008),
      cases of EC during the period 1996-2008 were identified. Medical records of all
      adults diagnosed with EC were identified and the pathology reviewed. The patients
      were then contacted for follow-up using a standardized questionnaire. RESULTS:
      Seven cases of EC (four in women) were identified, with a median follow-up of 45
      (23-79) months. The median age at diagnosis was 42 (22-70) years. Symptoms at
      diagnosis were abdominal pain (86%), nonbloody diarrhoea (57%), bloody diarrhoea
      (29%) and significant (>10%) weight loss (29%). Three patients gave a history of
      allergic reactions to drugs and four reported allergy to cows' milk. Endoscopic
      findings were nonspecific, ranging from oedema to small aphthous ulceration. An
      eosinophilic infiltrate was identified in the lamina propria in the initial
      colonic biopsy in all patients. Over the longer term, three patients experienced
      spontaneous resolution without treatment. Two continued to have mild diarrhoea
      and abdominal cramps but did not require medical therapy. Two patients required
      medical treatment by 5-aminosalicylic acid, with one requiring prednisone and
      azathioprine maintenance therapy. CONCLUSION: Eosinophilic colitis is a rare
      mostly self-limiting disease affecting middle-aged adults. It usually has a mild
      clinical course and drug treatment is not usually necessary. When required, drug
      treatment follows the standard medication for other inflammatory bowel disease.

PMID- 24138296
TI  - Solvent-based formulations for intravenous mouse pharmacokinetic studies:
      tolerability and recommended solvent dose limits.
AB  - 1. Modern high-throughput small molecule drug discovery requires rapid screening
      of the pharmacokinetic parameters of multiple candidate molecules in parallel.
      The mouse is often used for such screening, as are solvent-based intravenous
      formulations. Despite this, the intravenous toxicity of many commonly used
      solvents is unknown. The purpose of this investigation is to establish
      recommended no-observed-effect level (NOEL) and maximum tolerated dose (MTD) for
      several commonly used intravenous solvents in the CD-1 mouse. 2. The acute
      tolerability of polyethylene glycol 400, N-methylpyrrolidone, dimethyl sulfoxide,
      ethanol, dimethylacetamide and propylene glycol was established, along with
      combinations of polyethylene glycol 400 and/or ethanol and DMSO. Based on these
      data, an acute NOEL and recommended MTD is reported for each solvent or solvent
      combination. 3. These data can guide the use of these solvents to support single
      dose intravenous pharmacokinetic studies in mice. By establishing a defined dose
      tolerability range for the most commonly used intravenous solvents, undue pain
      and distress in animals can be avoided while maximizing the generation of
      critical pharmacokinetic data for project teams.

PMID- 24138297
TI  - Comment on methodological problems of 'Is there sufficient evidence to support
      the long-term efficacy of mineral trioxide aggregate for endodontic therapy in
      primary teeth?' by Anthonappa R P et al. (International Endodontic Journal, 46,
      198-204, 2013).

PMID- 24138298
TI  - Increased parental history of bipolar disorder in the United States: association
      with early age of onset.
AB  - OBJECTIVE: Early-onset bipolar (BP) disorder and other poor prognosis
      characteristics are more prevalent in patients from the United States than from
      the Netherlands and Germany (abbreviated as Europe). We explored the impact of
      parental loading for affective illness on onset and other characteristics of BP
      disorder. METHOD: Parental history for unipolar (UP) and bipolar (BP) depression
      and course of illness characteristics were obtained from self-report in adults
      (average age 42) with BP disorder. Illness characteristics were examined by chi2
      and multinomial logistic regression in relationship to the degree of parental
      loading: i) both parents negative; ii) one UP disorder; iii) one with BP
      disorder; and iv) both affected. RESULTS: After controlling for many poor
      prognosis factors, compared with those from Europe, patients from the United
      States had more iii) one parent with BP disorder and iv) both parents affected.
      An early age of onset of BP disorder was independently associated with this
      increased parental loading for affective disorder. CONCLUSION: Parental history
      of BP disorder and both parents with a mood disorder were more common in the
      United States than Europe and were associated with an early onset of bipolar
      disorder and other poor prognosis characteristics. These findings deserve
      replication and exploration of the potential mechanisms involved and their
      therapeutic implications.

PMID- 24138299
TI  - Chest pain in primary care: is the localization of pain diagnostically helpful in
      the critical evaluation of patients?--A cross sectional study.
AB  - BACKGROUND: Chest pain is a common complaint and reason for consultation in
      primary care. Traditional textbooks still assign pain localization a certain
      discriminative role in the differential diagnosis of chest pain. The aim of our
      study was to synthesize pain drawings from a large sample of chest pain patients
      and to examine whether pain localizations differ for different underlying
      etiologies. METHODS: We conducted a cross-sectional study including 1212
      consecutive patients with chest pain recruited in 74 primary care offices in
      Germany. Primary care providers (PCPs) marked pain localization and radiation of
      each patient on a pictogram. After 6 months, an independent interdisciplinary
      reference panel reviewed clinical data of every patient, deciding on the etiology
      of chest pain at the time of patient recruitment. PCP drawings were entered in a
      specially designed computer program to produce merged pain charts for different
      etiologies. Dissimilarities between individual pain localizations and differences
      on the level of diagnostic groups were analyzed using the Hausdorff distance and
      the C-index. RESULTS: Pain location in patients with coronary heart disease (CHD)
      did not differ from the combined group of all other patients, including patients
      with chest wall syndrome (CWS), gastro-esophageal reflux disease (GERD) or
      psychogenic chest pain. There was also no difference in chest pain location
      between male and female CHD patients. CONCLUSIONS: Pain localization is not
      helpful in discriminating CHD from other common chest pain etiologies.

PMID- 24138300
TI  - Malformation in index pregnancy in women with epilepsy is not followed by
      recurrence in subsequent pregnancy.
AB  - Use of antiepileptic drugs (AEDs) in pregnant women with epilepsy (WWE) is
      associated with an increased risk of major congenital malformations (MCM).
      Previous studies have suggested that WWE who had a malformation in their index
      pregnancy were at an increased risk of recurrence in future pregnancies. We aimed
      to assess the risk of recurrence of MCM in 1,616 WWE from Kerala Registry of
      Epilepsy and Pregnancy. The pregnancy outcome of women (n = 246) with two
      prospective pregnancies in the registry were analyzed. They had partial seizures
      with or without generalization (57.3%) or generalized seizures (42.7%).
      Polytherapy was used in 26.4% (index pregnancy) and 23.6% (follow-up pregnancy).
      The mean dosage of AED for valproate was 498 mg/day and carbamazepine was 555
      mg/day. The malformation rate in the index pregnancy was 8.5% (21/246) and in the
      follow-up pregnancy was 8.9% (22/246) with only one recurrence. There was no
      increased risk of MCM in follow-up pregnancy for those who had MCM in the index
      pregnancy (p = 0.70; OR 0.49; 95% CI 0.06-3.80). The use of any specific drug,
      continuation of the same drug or a change in drug therapy between two pregnancies
      did not alter the recurrence risk. 

PMID- 24138301
TI  - Formal assessment of the educational environment experienced by interns placed in
      rural hospitals in Western Australia.
AB  - INTRODUCTION: Increased numbers of rural hospital rotations for interns (first
      postgraduate year) are being created in Western Australia (WA). This study
      utilised the Postgraduate Hospital Educational Environment Measure (PHEEM), an
      internationally validated multidimensional questionnaire, to assess and compare
      the educational environment of five new or established rural sites and an urban
      teaching hospital. METHODS: The PHEEM was modified slightly: to make language
      appropriate for the WA context and to collect information about intern location.
      It was administered at the completion of each 10-week term over the first
      postgraduate year in 2009. RESULTS: A total of 147 completed PHEEM questionnaires
      were returned from 74 interns, evaluating a maximum of 210 individual 10-week
      terms (105 each from urban and combined rural). Average completion time was 6.4
      minutes. The median score for teaching was 45.0 (interquartile range 39.0, 50.0)
      in rural locations and 43.0 (37.5, 46.0) in urban locations (p=0.046). The median
      scores for autonomy were 39.0 (35.0, 45.0) and 39.0 (36.0, 41.5) (p=0.672) and
      for support median scores 33.0 (28.0, 35.0) and 31.0 (28.0, 33.0) (p=0.019) in
      rural and urban locations respectively. CONCLUSION: This study has utilised an
      Australian-appropriate version of the PHEEM and has provided the first
      confirmation that, in terms of educational environment, rural intern rotations
      compare favourably with those in urban settings in WA.

PMID- 24138302
TI  - Kinase inhibitors and immune check-point blockade for the treatment of metastatic
      melanoma and advanced cancer: synergistic or antagonistic?
AB  - In recent years, therapeutic approaches for many tumors have broadened or even
      shifted entirely from cytotoxic chemotherapy to specific targeting of
      dysregulated proteins (predominately kinases), and more recently, harnessing of
      the anti-tumor immune response. The most prominent example of this shift is the
      management of metastatic melanoma, where BRAF and MEK inhibition and CLTA-4
      blockade have established an entirely new standard of care in the last 3 years.
      Targeted kinase inhibition and immune checkpoint blockade have different
      strengths and weaknesses. Kinase inhibitors generally have rapid and impressive
      response rates but modest progression-free survival while immunotherapy can
      achieve durable tumor control, but is often associated with lower response rates
      and slower time to clinical benefit. These approaches would seem to be
      complementary however the results of early combination studies suggest that
      caution is advised when combining targeted kinase inhibition with immunotherapy.
      In this context, rigorous biomarker driven clinical trials are needed to further
      elucidate mechanisms of both benefit and toxicity. Depending on disease specific
      biology, it seems likely that both combination and sequential approaches of
      kinase inhibitors with immunotherapy will be required in order to harness the
      full potential of these approaches. 

PMID- 24138303
TI  - Up-regulation of RUNX2 in acute myeloid leukemia in a patient with an inherent
      RUNX2 haploinsufficiency and cleidocranial dysplasia.

PMID- 24138304
TI  - Outcome and risk factors of patients with Hodgkin Lymphoma who relapse or
      progress after autologous stem cell transplant.

PMID- 24138305
TI  - Cytomegalovirus retinitis in children and young adults with acute lymphoblastic
      leukemia in Lebanon.

PMID- 24138306
TI  - miR-29c down-regulation is associated with disease aggressiveness and poor
      survival in Chinese patients with chronic lymphocytic leukemia.
AB  - Aberrant expression of microRNAs in chronic lymphocytic leukemia (CLL) has been
      reported to be associated with clinical outcome and improve prognostic
      stratification. The aim of this study was to explore the association of miR-29c
      expression with clinical parameters and survival in 53 Chinese patients with CLL.
      We showed that the miR-29c expression level decreased significantly from early to
      advanced clinical stages, and was significantly lower in patients with beta(2)
      microglobulin higher than 3.5 mg/L or with disease progression or death. With the
      cut-off determined by receiver operating characteristic (ROC) curve analysis,
      optimizing concordance with immunoglobulin heavy chain (IgVH) mutation status,
      miR-29c negative and positive groups were defined as including 17 and 36
      patients, respectively. The miR-29c negative group had a higher percentage of
      patients with trisomy 12 or deletion of 11q or 17p (70.6% vs. 34.3%; p = 0.014)
      compared to the miR-29c positive group. The median progression-free survival and
      overall survival of the miR-29c negative group were 21 and 92 months,
      respectively, significantly shorter than in the miR-29c positive group (both not
      reached; p = 0.002 and p = 0.042, respectively), and miR-29c down-regulation was
      an independent prognostic factor for PFS. In conclusion, down-regulation of miR
      29c is associated with higher tumor burden and significantly predicts short
      survival in Chinese patients with CLL.

PMID- 24138307
TI  - Lenalidomide-induced cytokine release syndrome in a patient with multiple
      myeloma.

PMID- 24138308
TI  - Safety and tolerability of intrathecal liposomal cytarabine as central nervous
      system prophylaxis in patients with acute lymphoblastic leukemia.
AB  - Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in
      up to 15% of patients and is frequently associated with poor outcome. The purpose
      of our study was to evaluate the efficacy and safety of a slow-release liposomal
      formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients
      suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively
      treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal
      cytarabine on a compassionate use basis. After a median observation period of 23
      months (range 2-118) only two patients experienced a combined medullary
      leptomeningeal disease recurrence after primary diagnosis. Except for headache
      grade 2 in two patients, no specific toxicity attributable to IT liposomal
      cytarabine application was noted. Long-term neurological side effects were not
      observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears
      to be feasible and well tolerated.

PMID- 24138309
TI  - Lack of association of IDH1, IDH2 and DNMT3A mutations with outcome in older
      patients with acute myeloid leukemia treated with hypomethylating agents.

PMID- 24138310
TI  - Letting go is never easy: abscission and receptor-like protein kinases.
AB  - Abscission is the process by which plants discard organs in response to
      environmental cues/stressors, or as part of their normal development. Abscission
      has been studied throughout the history of the plant sciences and in numerous
      species. Although long studied at the anatomical and physiological levels,
      abscission has only been elucidated at the molecular and genetic levels within
      the last two decades, primarily with the use of the model plant Arabidopsis
      thaliana. This has led to the discovery of numerous genes involved at all steps
      of abscission, including key pathways involving receptor-like protein kinases
      (RLKs). This review covers the current knowledge of abscission research,
      highlighting the role of RLKs. [Figure: see text] John C. Walker (Corresponding
      author). 

PMID- 24138311
TI  - A structure-activity analysis of biased agonism at the dopamine D2 receptor.
AB  - Biased agonism offers an opportunity for the medicinal chemist to discover
      pathway-selective ligands for GPCRs. A number of studies have suggested that
      biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the
      treatment of neuropsychiatric disorders, including schizophrenia. As such, it is
      of great importance to gain insight into the SAR of biased agonism at this
      receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl
      (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This
      ligand shares structural similarity to cariprazine (2), a drug awaiting FDA
      approval for the treatment of schizophrenia, yet displays a distinct bias toward
      two different signaling end points. We synthesized a number of derivatives of 4
      with subtle structural modifications, including incorporation of cariprazine
      fragments. By combining pharmacological profiling with analytical methodology to
      identify and to quantify bias, we have demonstrated that efficacy and biased
      agonism can be finely tuned by minor structural modifications to the head group
      containing the tertiary amine, a tail group that extends away from this moiety,
      and the orientation and length of a spacer region between these two moieties. 

PMID- 24138312
TI  - I'll pick forgiving.
AB  - In this essay, the author gives voice to turning points in her life related to
      infidelity, mental illness, and forgiveness. By melding poetry, prose, dream
      journal entries, and medical case notes, she tells the story of how she became a
      single parent of a young man with mental illness. This narrative constitutes a
      defining moment in which she reframes an unforgivable relational transgression as
      an unforgettable opportunity for forgiveness. 

PMID- 24138313
TI  - The liver to abdominal area ratio (LAAR): a novel imaging score for
      prognostication in cirrhosis.
AB  - BACKGROUND: Anecdotally, liver size is important in determining prognosis in
      patients with end-stage liver disease (ESLD). AIMS: To assess if a ratio of liver
      area and abdominal area on cross-sectional imaging could accurately predict
      mortality in ESLD. METHODS: A retrospective-prospective cohort study was
      performed on patients with ESLD in a training set. The censor point used was date
      of patient death or liver transplant (LT). The liver to abdominal area ratio
      (LAAR) was calculated using the formula {LAAR = [liver area (cm(2))/abdominal
      area (cm(2))] * 100}. A validation set was collected from a different
      institution. RESULTS: Three hundred and sixteen patients were identified.
      Complete imaging and survival data were available in 158 subjects, 100 male
      (63%). The LAAR score detected progression to death/LT in our cohort (P < 0.003).
      Its prognostic accuracy at 90, 360 and 720 days, using the optimal cut-off
      (32.1), from baseline CT date to death/LT using the log-rank test was P = 0.28, P
      = 0.06 (OR 1.347, 95% CI 0.94-1.94) and P < 0.0001 (OR 1.89, 95% CI 1.25-2.85)
      respectively. On multivariate analysis, LAAR (P = 0.008), MELD (P = 0.004) and
      MELD-Na (P = 0.03) were independently associated with the primary study outcome
      measurement at 720 days. The validation set of 52 patients confirmed the utility
      of the LAAR to determine risk of death or need for LT, AUROC 0.89 (0.78-0.97),
      and P < 0.0001. CONCLUSIONS: The liver to abdominal area ratio (LAAR) score
      offers a new paradigm in disease modelling in end-stage liver disease (ESLD) and
      offers prognostic accuracy at 2 years from computer tomography (CT) imaging.

PMID- 24138314
TI  - A novel type of N-acetylglutamate synthase is involved in the first step of
      arginine biosynthesis in Corynebacterium glutamicum.
AB  - BACKGROUND: Arginine biosynthesis in Corynebacterium glutamicum consists of eight
      enzymatic steps, starting with acetylation of glutamate, catalysed by N
      acetylglutamate synthase (NAGS). There are different kinds of known NAGSs, for
      example, "classical" ArgA, bifunctional ArgJ, ArgO, and S-NAGS. However, since C.
      glutamicum possesses a monofunctional ArgJ, which catalyses only the fifth step
      of the arginine biosynthesis pathway, glutamate must be acetylated by an as of
      yet unknown NAGS gene. RESULTS: Arginine biosynthesis was investigated by
      metabolome profiling using defined gene deletion mutants that were expected to
      accumulate corresponding intracellular metabolites. HPLC-ESI-qTOF analyses gave
      detailed insights into arginine metabolism by detecting six out of seven
      intermediates of arginine biosynthesis. Accumulation of N-acetylglutamate in all
      mutants was a further confirmation of the unknown NAGS activity. To elucidate the
      identity of this gene, a genomic library of C. glutamicum was created and used to
      complement an Escherichia coli DeltaargA mutant. The plasmid identified, which
      allowed functional complementation, contained part of gene cg3035, which contains
      an acetyltransferase domain in its amino acid sequence. Deletion of cg3035 in the
      C. glutamicum genome led to a partial auxotrophy for arginine. Heterologous
      overexpression of the entire cg3035 gene verified its ability to complement the
      E. coli DeltaargA mutant in vivo and homologous overexpression led to a
      significantly higher intracellular N-acetylglutamate pool. Enzyme assays
      confirmed the N-acetylglutamate synthase activity of Cg3035 in vitro. However,
      the amino acid sequence of Cg3035 revealed no similarities to members of known
      NAGS gene families. CONCLUSIONS: The N-acetylglutamate synthase Cg3035 is able to
      catalyse the first step of arginine biosynthesis in C. glutamicum. It represents
      a novel class of NAGS genes apparently present only in bacteria of the suborder
      Corynebacterineae, comprising amongst others the genera Corynebacterium,
      Mycobacterium, and Nocardia. Therefore, the name C-NAGS (Corynebacterineae-type
      NAGS) is proposed for this new family.

PMID- 24138315
TI  - Removable dental prosthesis splint. An occlusal device for nocturnal bruxing
      partial denture users.
AB  - Nocturnal bruxing is a parafunctional activity of the masticatory system that may
      create problems for removable dental prosthesis (RDP) users. Such problems may
      include root fractures, increased mobility of abutment teeth, excessive wear of
      resin denture teeth, minor connector bending, or denture base cracking. This
      clinical report presents an occlusal device fabricated for an RDP patient. The
      device used existing ERA attachments for added retention designed with the
      intended purpose of protecting the definitive fixed and RDP from damage due to
      nocturnal bruxing activity and providing for even distribution of parafunctional
      forces. 

PMID- 24138316
TI  - alpha-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta
      1-42 fibril-induced microglial activation.
AB  - OBJECTIVES: To examine the antineuroinflammatory and neuroprotective activity of
      alpha-iso-cubebenol and its molecular mechanism of action in amyloid beta (Abeta)
      1-42 fibril-stimulated microglia. METHODS: Abeta 1-42 fibrils were used to induce
      a neuroinflammatory response in murine primary microglia and BV-2 murine
      microglia cell lines. Cell viability was monitored by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay, protein expression and phosphorylation
      were determined by Western blot analysis, and matrix metalloproteinase-9 (MMP-9)
      activity was determined by gelatin zymography assay. In addition, prostaglandin
      E2 (PGE2), pro-inflammatory cytokines and chemokines were measured by ELISA, and
      the transactivity of nuclear factor (NF)-kappaB was determined by a reporter
      assay. KEY FINDINGS: alpha-Iso-cubebenol significantly inhibited Abeta 1-42
      fibril-induced MMP-9, inducible nitric oxide synthase and cyclooxygenase-2
      expressions and activity, without affecting cell viability. alpha-Iso-cubebenol
      also suppressed the production of tumour necrosis factor-alpha, IL-1beta, IL-6,
      monocyte chemoattractant protein-1 and reactive oxygen species in a dose
      dependent manner, while decreasing the nuclear translocation and transactivity of
      NF-kappaB by inhibiting the phosphorylation and degradation of the inhibitor of
      kappaB (IkappaB)alpha. alpha-Iso-cubebenol suppressed the phosphorylation of
      mitogen-activated protein kinase (MAPK) in Abeta 1-42 fibril-stimulated
      microglia. Primary cortical neurons were protected by the inhibitory effect of
      alpha-iso-cubebenol on Abeta 1-42 fibril-induced neuroinflammatory response.
      CONCLUSIONS: alpha-Iso-cubebenol suppresses Abeta 1-42 fibril-induced
      neuroinflammatory molecules in primary microglia via the suppression of NF
      kappaB/inhibitor of kappaBalpha and MAPK. Importantly, the antineuroinflammatory
      potential of alpha-iso-cubebenol is critical for neuroprotection.

PMID- 24138317
TI  - Building Trust to Work with Children after a Severe Traumatic Accident.
AB  - Abstract Trust is integral to nursing; yet little is known about how nurses
      establish trust when working with patients. This grounded theory study explored
      nurses' perspectives of how to build trust with a child and family in the context
      of paediatric acute health care. Seven paediatric acute care nurses were asked
      what they did when they cared for a child admitted to an acute care ward from
      emergency department or intensive care unit following a severe traumatic
      accident. Building trust emerged as the basic social process for an effective
      working-relationship between a nurse and family to promote the rehabilitation of
      the child. This paper argues that building trust is critical to nurses developing
      a working relationship with both child and family to promote optimal health, and
      enables nurses to effectively step out and handover the care of the child to the
      family.

PMID- 24138318
TI  - Death within the first year after kidney transplantation--an observational cohort
      study.
AB  - The risk of death within the first year postkidney transplantation is not well
      described in the contemporary era. We extracted data on all kidney transplant
      procedures performed in England between April 2001 and March 2012. Data linkage
      analysis was performed between Hospital Episode Statistics and the Office for
      National Statistics to identify all deaths. Cox proportional hazard models were
      performed to identify factors associated with 1-year mortality. 566 deaths (3.0%)
      occurred within the first year post-transplant (from 19,103 kidney transplant
      procedures analysed). Infection, cardiovascular events and malignancy were
      classified in 21.6%, 18.3% and 7.4% of death certificates, respectively. Among
      recipients with prior myocardial infarct history who died within the first year,
      38.8% of deaths were attributed to a cardiac-related event. Malignancy-related
      death was responsible for 61.5% of 1-year mortality for allograft recipients with
      pretransplant cancer history. 22.1% of deaths included kidney failure as a
      contributory factor on the death certificate (3.3% specifically stated allograft
      failure). Variables associated with 1-year mortality included deceased-donor
      kidney, increasing age, residence in socioeconomically deprived area and history
      of select medical comorbidities pre-operatively. We conclude 1-year mortality
      postkidney transplantation is low, but in select allograft recipients, the risk
      of death increases considerably.

PMID- 24138319
TI  - The protective role of antiplatelet treatment against ulcer formation due to
      argon plasma coagulation in patients treated for chronic radiation proctitis.
AB  - AIM: Following treatment with argon plasma coagulation (APC), rectal ulceration
      is seen in approximately 50% of patients with haemorrhagic chronic radiation
      proctitis (CRP). This study aimed to assess the frequency of rectal ulcers
      (defined as a mucosal defect of 3 mm or more in diameter) in relation to the use
      of antiplatelet treatment for concomitant cardiovascular disease. METHOD: Sixty
      two patients with CRP were included in this retrospective study. Patients
      underwent pelvic irradiation due to prostate cancer (n = 28), cervical cancer (n
      = 16), endometrial cancer (n = 17) or rectal cancer (n = 1). APC was performed in
      all patients. Control endoscopies were performed at 8 and 16 weeks after
      enrolment. RESULTS: Rectal ulcers were observed after APC in 35 (56%) patients.
      They were symptomatic in 5 and asymptomatic in 30. The 20 (32%) patients who were
      on antiplatelet therapy had a significantly lower risk of ulceration after APC
      (OR = 0.21; 95% CI 0.049-0.91; P = 0.019). The number of symptomatic ulcers (5%
      vs 10%; P = 1.0) and asymptomatic ulcers alone (30% vs 58%; P = 0.06) was also
      lower in patients respectively taking and not taking antiplatelet therapy, but
      these differences did not reach statistical significance. CONCLUSION: Argon
      plasma coagulation-related ulceration in patients treated for CRP is less common
      when concomitant antiplatelet treatment is administered. This preliminary finding
      suggests that antiplatelet therapy may benefit patients treated with APC for CRP.

PMID- 24138320
TI  - The effect of TRPM7 suppression on the proliferation, migration and osteogenic
      differentiation of human dental pulp stem cells.
AB  - AIM: To investigate the role of the Ca(2+) -Mg(2+) ion channel TRPM7 in the
      proliferation, migration and osteogenic differentiation of human dental pulp stem
      cells (hDPSCs). METHODOLOGY: Immunohistochemistry was used to localize expression
      of TRPM7 in human dental pulp tissues and in cultured hDPSCs. Isolated hDPSCs
      were infected with recombinant lentiviruses expressing short hairpin RNA (shRNA)
      specific for TRPM7, or control shRNA, in order to suppress TRPM7 mRNA expression
      and investigate its functional role. The proliferation of the shRNA-infected
      hDPSCs was evaluated using both an MTT assay to measure viable cell numbers and
      cell cycle analysis. Cell migration was assessed using a transwell assay. The
      dynamic mRNA expression of TRPM7 during osteogenic differentiation of hDPSCs and
      the effect of shRNA specific for TRPM7 on hDPSC osteogenic differentiation were
      evaluated by real-time PCR. RESULTS: TRPM7 expression was widespread in human
      dental pulp tissue and was detected mainly in the cytomembrane and cytoplasm of
      hDPSCs. Suppression of TRPM7 inhibited both the proliferation and the migratory
      capacity of hDPSCs. TRPM7 mRNA expression was elevated during osteogenic
      differentiation of hDPSCs. TRPM7-specific shRNA inhibited osteogenic
      differentiation of hDPSCs, with downregulated mRNA expression of the osteogenic
      markers alkaline phosphatase (ALP), dentine sialophosphoprotein (DSPP), bone
      sialoprotein (BSP), runt-related transcription factor (RUNX2) and osterix (OSX).
      CONCLUSIONS: TRPM7 was involved in the regulation of hDPSC proliferation,
      migration and osteogenic differentiation and may play a role in the dental pulp
      repair process.

PMID- 24138321
TI  - Anti-laminin-332 mucous membrane pemphigoid in a 9-year old girl.
AB  - Mucous membrane pemphigoid (MMP), an autoimmune subepithelial blistering disease
      that predominantly affects the mucous membranes, is usually diagnosed in elderly
      adults. Early diagnosis of MMP is crucial because it tends to run a chronic and
      progressive course with the potential for devastating scarring of the mucous
      membranes that may lead to blindness and airway compromise. A subtype of MMP,
      anti-laminin-332 MMP, is a rare blistering disorder in which autoantibodies are
      directed against laminin-332 (formerly epiligrin), a structural protein of the
      epidermal basement membrane. Herein we report what we believe to be the youngest
      patient diagnosed with anti-laminin-332 MMP, a 9-year-old girl with disease
      affecting only the oral, pharyngeal, and laryngeal mucosa, with no skin
      involvement. 

PMID- 24138323
TI  - Maternal and perinatal outcomes following peripartum hysterectomy from a single
      tertiary centre.
AB  - BACKGROUND: We investigated the indications for and maternal and perinatal
      outcomes following peripartum hysterectomy in a single large tertiary centre.
      MATERIALS AND METHODS: All cases of peripartum hysterectomy between 2000 and 2011
      were investigated. Data regarding maternal demographics, previous obstetric and
      gynaecological history, indications for hysterectomy, and details of haemorrhage,
      surgical complications and neonatal outcomes were collected. RESULTS: There were
      47 cases of peripartum hysterectomy of 55 262 births giving an incidence of 0.85
      per 1000 births. Forty-one cases were total hysterectomies, while six were
      subtotal procedures. A total of 70.2% of cases were performed because of a
      morbidly adherent placenta, 27.7% for uterine atony and 2.1% for uterine rupture.
      The median estimated blood loss was 7290 mL. The overall surgical complication
      rate was 44.6% with bladder injury (19.1%) and sepsis (12.8%) commonest.
      Intensive care admission was required in 57.4% of women. CONCLUSIONS: Peripartum
      hysterectomy is a major procedure carrying a high morbidity rate. In this series,
      maternal survival was 100%.

PMID- 24138322
TI  - Regulation of vascular smooth muscle cell phenotype in three-dimensional
      coculture system by Jagged1-selective Notch3 signaling.
AB  - The modulation of vascular smooth muscle cell (VSMC) phenotype is an essential
      element to fabricate engineered conduits of clinical relevance. In vivo, owing to
      their close proximity, endothelial cells (ECs) play a role in VSMC phenotype
      switching. Although considerable progress has been made in vascular tissue
      engineering, significant knowledge gaps exist on how the contractile VSMC
      phenotype is induced at the conclusion of the tissue fabrication process. The
      objectives of this study were as follows: (1) to establish ligand presentation
      modes on transcriptional activation of VSMC-specific genes, (2) to develop a
      three-dimensional (3D) coculture model using human coronary artery smooth muscle
      cells (HCASMCs) and human coronary artery endothelial cells (HCAECs) on porous
      synthetic scaffolds and, (3) to investigate EC-mediated Notch signaling in 3D
      cultures and the induction of the HCASMC contractile phenotype. Whereas
      transcriptional activation of VSMC-specific genes was not induced by presenting
      soluble Jagged1 and Jagged1 bound to protein G beads, a direct link between HCAEC
      bound Jagged1 and HCASMC differentiation genes was observed. Our 3D culture
      results showed that HCASMCs seeded to scaffolds and cultured for up to 16 days
      readily attached, infiltrated the scaffold, proliferated, and formed dense
      confluent layers. HCAECs, seeded on top of an HCASMC layer, formed a distinct,
      separate monolayer with cell-type partitioning, suggesting that HCAEC growth was
      contact inhibited. While we observed EC monolayer formation with 200,000
      HCAECs/scaffold, seeding 400,000 HCAECs/scaffold revealed the formation of cord
      like structures akin to angiogenesis. Western blot analyses showed that 3D
      coculture induced an upregulation of Notch3 receptor in HCASMCs and its ligand
      Jagged1 in HCAECs. This was accompanied by a corresponding induction of the
      contractile HCASMC phenotype as demonstrated by increased expression of smooth
      muscle-alpha-actin (SM-alpha-actin) and calponin. Knockdown of Jagged1 with siRNA
      showed a reduction in SM-alpha-actin and calponin in cocultures, identifying a
      link between Jagged1 and the expression of contractile proteins in 3D cocultures.
      We therefore conclude that the Notch3 signaling pathway is an important regulator
      of VSMC phenotype and could be targeted when fabricating engineered vascular
      tissues. 

PMID- 24138324
TI  - Optimizing the use of rainbow trout hepatocytes for bioaccumulation assessments
      with fish.
AB  - Biotransformation rates measured using cryopreserved trout hepatocytes can be
      extrapolated to the whole animal to predict metabolism impacts on chemical
      bioaccumulation. Future use of these methods within a regulatory context
      requires, however, that they be optimized and standardized. Specifically,
      questions exist concerning gender differences in metabolism, cryopreservability
      of cells, and the accuracy of in vitro-in vivo scaling factors. 2. In this study,
      we evaluated hepatocytes from juvenile male and female trout. No gender
      differences in cell size, protein abundance, cytochrome P450 content,
      ethoxyresorufin-O-deethylase activity, uridine diphosphate
      glucuronosyltransferase activity or intrinsic clearance of pyrene were observed
      for freshly isolated hepatocytes. There was a small difference in measured
      glutathione-S-transferase activity (<25%; males > females). 3. Cells were
      cryopreserved by two methods: direct placement into liquid N2 vapor and
      controlled, slow-rate freezing. Comparable live recovery and enzymatic activity
      were observed regardless of freezing method or gender. Cells cryopreserved in
      liquid N2 vapor exhibited activity levels similar to those of freshly isolated
      cells, although there were small but significant differences in pyrene clearance
      and glutathione-S-transferase activity (frozen < fresh). Hepatocellularity values
      did not differ by sex. 4. These results suggest that hepatocytes from male and
      female juvenile trout may be used interchangeably for in vitro-in vivo metabolism
      extrapolations.

PMID- 24138326
TI  - Mapping nanoscale variations in photochemical damage of polymer/fullerene solar
      cells with dissipation imaging.
AB  - We use frequency-modulated electrostatic force microscopy to track changes in
      cantilever quality factor (Q) as a function of photochemical damage in a model
      organic photovoltaic system poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5
      b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4
      b]thiophenediyl]] (PTB7) and 3'H-cyclopropa[8,25][5,6]fullerene-C71-D5h(6)-3'
      butanoic acid, 3'-phenyl-, methyl ester (PC71BM). We correlate local Q factor
      imaging with macroscopic device performance and show that, for this system,
      changes in cantilever Q correlate well with changes in external quantum
      efficiency and can thus be used to monitor local photochemical damage over the
      entire functional lifetime of a PTB7:PC71BM solar cell. We explore how Q imaging
      is affected by the choice of cantilever resonance frequency. Finally, we use Q
      imaging to elucidate the differences in the evolution of nanoscale structure in
      the photochemical damage occurring in PTB7:PC71BM solar cells processed with and
      without the solvent additive 1,8-diiodooctane (DIO). We show that processing with
      DIO not only yields a preferable morphology for uniform performance across the
      surface of the device but also enhances the stability of PTB7:PC71BM solar cells
      an effect that can be predicted based on the local Q images. 

PMID- 24138325
TI  - An evidence-based shared decision making programme on the prevention of
      myocardial infarction in type 2 diabetes: protocol of a randomised-controlled
      trial.
AB  - BACKGROUND: Lack of patient involvement in decision making has been suggested as
      one reason for limited treatment success. Concepts such as shared decision making
      may contribute to high quality healthcare by supporting patients to make informed
      decisions together with their physicians.A multi-component shared decision making
      programme on the prevention of heart attack in type 2 diabetes has been
      developed. It aims at improving the quality of decision-making by providing
      evidence-based patient information, enhancing patients' knowledge, and supporting
      them to actively participate in decision-making. In this study the efficacy of
      the programme is evaluated in the setting of a diabetes clinic. METHODS/DESIGN: A
      single blinded randomised-controlled trial is conducted to compare the shared
      decision making programme with a control-intervention. The intervention consists
      of an evidence-based patient decision aid on the prevention of myocardial
      infarction and a corresponding counselling module provided by diabetes educators.
      Similar in duration and structure, the control-intervention targets nutrition,
      sports, and stress coping. A total of 154 patients between 40 and 69 years of age
      with type 2 diabetes and no previous diagnosis of ischaemic heart disease or
      stroke are enrolled and allocated either to the intervention or the control
      intervention. Primary outcome measure is the patients' knowledge on benefits and
      harms of heart attack prevention captured by a standardised knowledge test. Key
      secondary outcome measure is the achievement of treatment goals prioritised by
      the individual patient. Treatment goals refer to statin taking, HbA1c-, blood
      pressure levels and smoking status. Outcomes are assessed directly after the
      counselling and at 6 months follow-up. Analyses will be carried out on intention
      to-treat basis. Concurrent qualitative methods are used to explore intervention
      fidelity and to gain insight into implementation processes. DISCUSSION:
      Interventions to facilitate evidence-based shared decision making represent an
      innovative approach in diabetes care. The results of this study will provide
      information on the efficacy of such a concept in the setting of a diabetes clinic
      in Germany. TRIAL REGISTRATION: ISRCTN84636255.

PMID- 24138327
TI  - Risk-taking behavior in juvenile myoclonic epilepsy.
AB  - OBJECTIVE: Patients with juvenile myoclonic epilepsy (JME) often present with
      risk-taking behavior, suggestive of frontal lobe dysfunction. Recent studies
      confirm functional and microstructural changes within the frontal lobes in JME.
      This study aimed at characterizing decision-making behavior in JME and its
      neuronal correlates using functional magnetic resonance imaging (fMRI). METHODS:
      We investigated impulsivity in 21 JME patients and 11 controls using the Iowa
      Gambling Task (IGT), which measures decision making under ambiguity. Performance
      on the IGT was correlated with activation patterns during an fMRI working memory
      task. RESULTS: Both patients and controls learned throughout the task. Post hoc
      analysis revealed a greater proportion of patients with seizures than seizure
      free patients having difficulties in advantageous decision making, but no
      difference in performance between seizure-free patients and controls. Functional
      imaging of working memory networks showed that overall poor IGT performance was
      associated with an increased activation in the dorsolateral prefrontal cortex
      (DLPFC) in JME patients. Impaired learning during the task and ongoing seizures
      were associated with bilateral medial prefrontal cortex (PFC) and
      presupplementary motor area, right superior frontal gyrus, and left DLPFC
      activation. SIGNIFICANCE: Our study provides evidence that patients with JME and
      ongoing seizures learn significantly less from previous experience. Interictal
      dysfunction within "normal" working memory networks, specifically, within the
      DLPFC and medial PFC structures, may affect their ability to learn.

PMID- 24138328
TI  - Invasive fungal infections in lymphoproliferative disorders: a monocentric
      retrospective experience.
AB  - Invasive fungal infections (IFIs) seem to be a relevant cause of morbidity and
      mortality in patients with chronic lymphoproliferative disorders. We studied
      retrospectively the epidemiology, clinical manifestations and outcome of invasive
      fungal infections in 42 patients with lymphoproliferative diseases, treated
      between January 2004 and February 2012 for probable or proven IFI. In our entire
      population (1355 patients) of chronic lymphoproliferative malignancies, the
      incidence of probable/proven IFI was 3% (molds 2.3%, yeasts 0.5%, mixed
      infections 0.2%). Eight patients developed a yeast infection documented by blood
      cultures in seven cases and by the microscopic observation of Candida spp. in the
      vitreum after vitrectomy in one case. Among molds we diagnosed three proven
      infections by histologic evidence of Aspergillus spp. (n = 2) and Mucor (n = 1)
      in the lung and 28 probable mycoses. Three mixed infections from both molds and
      yeasts were also observed. Twenty-two cases showed positivity of galactomannan
      antigen in the serum (n = 16), in bronchoalveolar lavage (BAL) fluid (n = 4) or
      in both (n = 2). Cultures were positive in 11 cases. The overall rate of response
      to therapy was 64%. Fungal-attributable mortality rate was 17%, with a
      significant difference between molds and yeasts (16% vs. 25%, p = 0.03). At
      univariate analysis, the only risk factors related to mortality were severe and
      prolonged neutropenia (p = 0.003) and age (p = 0.03). Among molds, the rapid
      start of antifungals was probably partially responsible, together with new drugs,
      for the reduction of mortality, despite the severe immunosuppression of these
      patients.

PMID- 24138329
TI  - Rituximab: how evidence based medicine can change our clinical practice.

PMID- 24138330
TI  - Improvement in survival of diffuse large B-cell lymphoma in relation to age,
      gender, International Prognostic Index and extranodal presentation: a population
      based Swedish Lymphoma Registry study.
AB  - Our aim was to describe a large population-based cohort of diffuse large B-cell
      lymphoma (DLBCL) during the last decade, evaluating possible improvement in
      survival and to identify subgroups in need of novel treatment strategies. The
      study population encompassed all patients diagnosed with DLBCL in Sweden from
      2000 through 2010. Altogether 5349 patients were identified. There was no
      increase in incidence for females, but for males there was an estimated yearly
      increase in incidence by 0.019 per 10 000. When adjusted for age and gender, the
      improvement in overall survival for the whole group was estimated at 4.5% per
      year, most prominent in the age group 60-78 years, and in patients with good
      performance status. In this large dataset, we were able to detect a clear
      improvement in overall survival in DLBCL, although restricted to specific
      prognostic subgroups, and to identify specific disease presentations that
      significantly affect overall survival.

PMID- 24138331
TI  - High-dose therapy and autologous hematopoietic stem cell transplant in T-cell
      lymphoma: a single center experience.
AB  - We report here the long-term outcome of autologous stem cell transplant in
      peripheral T-cell lymphoma (PTCL). Forty-three consecutive patients with PTCL
      diagnosed between 2000 and 2011 were treated with high-dose chemotherapy (HDCT)
      and autologous stem cell transplant (ASCT) in our center. Diagnoses included PTCL
      not otherwise specified (n = 19), anaplastic large cell lymphoma (n = 11),
      angioimmunoblastic T-cell lymphoma (n = 5), enteropathy-associated T-cell
      lymphoma (n = 5) and other rare subtypes (n = 3). Thirty-six patients with a
      median age of 50 years (range 22-65) were transplanted in first response and
      seven after relapse. After a median follow-up of 63 months, estimated overall
      survival at 12 years was 40%, progression-free survival at 12 years was 34% and
      event-free survival at 12 years was 30%. On univariate analysis, age less than 50
      years and no B symptoms at diagnosis were significantly associated with prolonged
      overall and progression-free-survival. HDCT/ASCT for peripheral T-cell lymphoma
      can lead to long-term survival for patients responding to induction chemotherapy.

PMID- 24138332
TI  - The nanoparticulate Quillaja saponin KGI exerts anti-proliferative effects by
      down-regulation of cell cycle molecules in U937 and HL-60 human leukemia cells.
AB  - Cancer cells are characterized by uncontrolled replication involving loss of
      control of cyclin dependent kinases (CDKs) and cyclins, and by abolished
      differentiation. In this study we introduce KGI, which is a nanoparticle with a
      Quillaja saponin as an active molecule. By the use of RNA array analysis and
      confirmation at the protein level, we show that KGI affects myeloid leukemia
      cells (in particular, the U937 monoblast cancer cell) by the following
      mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down
      regulation of key molecules at check points between G1/S and G2/M phases, (C)
      reduction of thymidine kinase activity, followed by (D) exit to differentiation
      and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia
      cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the
      drug was removed. The cancer cells did not revert to replication over the
      following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits
      proliferation and promotes differentiation in leukemic cells by interfering with
      the cell cycle process.

PMID- 24138334
TI  - Inhaled corticosteroids for chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Current guidelines recommend the use of inhaled long-acting
      bronchodilators, inhaled corticosteroids (ICSs) and their combinations for
      maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease
      (COPD); however, it is questionable whether all COPD patients should be treated,
      as the long-term use of ICSs is accompanied by side effects. AREAS COVERED: This
      article reviews the evidence about the effects of ICSs in the treatment of COPD.
      It mainly focuses on meta-analyses of published data and pooled analyses of
      primary data. It also offers an overview of pipeline developments. EXPERT
      OPINION: There is now more evidence that there are subsets of patients (mainly,
      frequent exacerbators with predominant chronic bronchitis and those with overlap
      between COPD and asthma) with a favorable response to treatment with ICSs (i.e.,
      reduced progression of lung function loss, reduced exacerbation rate and improved
      health-related quality of life). Therefore, nowadays, the right question is not
      whether ICSs should not be used at all unless patients have concomitant asthma,
      but, instead, which COPD patient can benefit from a therapy with ICSs.
      Unfortunately, however, the number of studies that have investigated the clinical
      features that might predict corticosteroid response in COPD is still inadequate.

PMID- 24138333
TI  - Sham control methods used in ear-acupuncture/ear-acupressure randomized
      controlled trials: a systematic review.
AB  - Ear-acupuncture/ear-acupressure (EAP) has been used for a range of health
      conditions with numerous randomized controlled trials (RCTs) investigating its
      efficacy and safety. However, the design of sham interventions in these RCTs
      varied significantly. This study systematically reviewed RCTs on EAP for all
      clinical conditions involving a number of sham EAPs as a control intervention.
      The review is guided by the Cochrane Handbook for Systematic Reviews of
      Interventions 5.1.0 and investigated the types and differences of sham EAP
      interventions. Four electronic English databases (The Cochrane Library, PubMed,
      Embase, CINAHL(r)) and two Chinese databases (CQVIP, CNKI) were searched in
      December 2012 and 55 published RCTs comparing real and sham EAP for any clinical
      condition were included. Characteristics of participants, real and sham
      interventions, and outcomes were extracted. Four types of sham methods were
      identified. Among the 55 RCTs, 25 studies involved treatment on nonspecific ear
      acupoints as the sham method; seven studies used nonacupoints on the ear; nine
      studies selected placebo needles or placebo ear-acupressure on the same ear
      acupoints for the real treatment; 10 studies employed pseudo-intervention; and
      five studies combined two of the above methods to be the sham control. Other
      factors of treatment such as number of points, treatment duration, and frequency
      also varied greatly. Risk of bias assessment suggests that 32 RCTs were "high
      risk" in terms of participants blinding, and 45 RCTs were "high risk" in terms of
      personnel blinding. Meta-analysis was not conducted due to the high clinical
      heterogeneity across included studies. No relationship was found between the sham
      designs and efficacy outcomes, or between the sham types and dropout rate. No
      solid conclusion of which design is the most appropriate sham control of EAP
      could be drawn in this review.

PMID- 24138335
TI  - Combining self-affirmation with the extended parallel process model: the
      consequences for motivation to eat more fruit and vegetables.
AB  - There is potential for fruitful integration of research using the Extended
      Parallel Process Model (EPPM) with research using Self-affirmation Theory.
      However, to date no studies have attempted to do this. This article reports an
      experiment that tests whether (a) the effects of a self-affirmation manipulation
      add to those of EPPM variables in predicting intentions to improve a health
      behavior and (b) self-affirmation moderates the relationship between EPPM
      variables and intentions. Participants (N = 80) were randomized to either a self
      affirmation or control condition prior to receiving personally relevant health
      information about the risks of not eating at least five portions of fruit and
      vegetables per day. A hierarchical regression model revealed that efficacy,
      threat * efficacy, self-affirmation, and self-affirmation * efficacy all uniquely
      contributed to the prediction of intentions to eat at least five portions per
      day. Self-affirmed participants and those with higher efficacy reported greater
      motivation to change. Threat predicted intentions at low levels of efficacy, but
      not at high levels. Efficacy had a stronger relationship with intentions in the
      nonaffirmed condition than in the self-affirmed condition. The findings indicate
      that self-affirmation processes can moderate the impact of variables in the EPPM
      and also add to the variance explained. We argue that there is potential for
      integration of the two traditions of research, to the benefit of both. 

PMID- 24138336
TI  - Genomic regions underlying agronomic traits in linseed (Linum usitatissimum L.)
      as revealed by association mapping.
AB  - The extreme climate of the Canadian Prairies poses a major challenge to improve
      yield. Although it is possible to breed for yield per se, focusing on yield
      related traits could be advantageous because of their simpler genetic
      architecture. The Canadian flax core collection of 390 accessions was genotyped
      with 464 simple sequence repeat markers, and phenotypic data for nine agronomic
      traits including yield, bolls per area, 1,000 seed weight, seeds per boll, start
      of flowering, end of flowering, plant height, plant branching, and lodging
      collected from up to eight environments was used for association mapping. Based
      on a mixed model (principal component analysis (PCA) + kinship matrix (K)), 12
      significant marker-trait associations for six agronomic traits were identified.
      Most of the associations were stable across environments as revealed by
      multivariate analyses. Statistical simulation for five markers associated with
      1000 seed weight indicated that the favorable alleles have additive effects. None
      of the modern cultivars carried the five favorable alleles and the maximum number
      of four observed in any accessions was mostly in breeding lines. Our results
      confirmed the complex genetic architecture of yield-related traits and the
      inherent difficulties associated with their identification while illustrating the
      potential for improvement through marker-assisted selection. 

PMID- 24138337
TI  - Serum neopterin and soluble CD163 as markers of macrophage activation in
      paracetamol (acetaminophen)-induced human acute liver injury.
AB  - BACKGROUND: Macrophage activation is implicated in the pathogenesis of the
      systemic inflammatory response syndrome (SIRS) following paracetamol
      (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and
      reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163)
      is a marker of alternatively activated M2 macrophages. AIM: To examine neopterin
      and sCD163 levels in a cohort of acute liver injury patients. METHODS:
      Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were
      enrolled. Neopterin and sCD163 levels were measured by ELISA. RESULTS: A total of
      24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore
      acute liver failure. Both neopterin and sCD163 levels were significantly higher
      in PODs compared with chronic liver disease (neopterin P < 0.001, sCD163 P =
      0.038) and healthy (both P < 0.001) controls. Admission neopterin levels were
      significantly higher in PODs: with HE (P = 0.001); with the SIRS (P = 0.005); who
      required renal replacement therapy (P = 0.003); who died or required liver
      transplantation (P = 0.006; AUROC 78.6% (95% CI 62.2-94.9%). Serum sCD163 levels
      were significantly higher in those PODs with the SIRS (P = 0.033) on admission,
      and were higher in those PODs who died or required OLT (P = 0.024). Both
      admission neopterin and sCD163 levels in PODs correlated with organ failure
      scores but not with serum ALT. There was no significant correlation between
      neopterin and sCD163 values. CONCLUSIONS: Both serum neopterin and sCD163 levels
      are significantly elevated following paracetamol overdose, and reflect the degree
      of macrophage activation in this condition. Serum neopterin in particular may
      have value as an early proxy marker of macrophage activation following
      paracetamol overdose.

PMID- 24138338
TI  - Metal-organic framework-immobilized polyhedral metal nanocrystals: reduction at
      solid-gas interface, metal segregation, core-shell structure, and high catalytic
      activity.
AB  - For the first time, this work presents surfactant-free monometallic and
      bimetallic polyhedral metal nanocrystals (MNCs) immobilized to a metal-organic
      framework (MIL-101) by CO-directed reduction of metal precursors at the solid-gas
      interface. With this novel method, Pt cubes and Pd tetrahedra were formed by CO
      preferential bindings on their (100) and (111) facets, respectively. PtPd
      bimetallic nanocrystals showed metal segregation, leading to Pd-rich core and Pt
      rich shell. Core-shell Pt@Pd nanocrystals were immobilized to MIL-101 by seed
      mediated two-step reduction, representing the first example of core-shell MNCs
      formed using only gas-phase reducing agents. These MOF-supported MNCs exhibited
      high catalytic activities for CO oxidation. 

PMID- 24138340
TI  - Using accreditation standards as a framework to evaluate and improve a community
      based diabetes self-management education program.
AB  - Diabetes self-management education is an essential component of diabetes clinical
      management, and community-based programs are an effective intervention for
      improving glycemic control among adults living with diabetes. The National
      Standards for Diabetes Self-Management Education and Support are designed to
      define quality diabetes self-management education and support, and to assist
      diabetes educators to provide evidence-based education and self-management
      support. These standards are used in the field for recognition and accreditation.
      This article presents the results of a program evaluation conducted by the Center
      for Urban Health at the Thomas Jefferson University and Hospital, examines the
      outcomes of the community-based diabetes self-management program, and uses the
      standards as the evaluation framework.

PMID- 24138339
TI  - Comprehensive discovery and characterization of small RNAs in Corynebacterium
      glutamicum ATCC 13032.
AB  - BACKGROUND: Recent discoveries on bacterial transcriptomes gave evidence that
      small RNAs (sRNAs) have important regulatory roles in prokaryotic cells. Modern
      high-throughput sequencing approaches (RNA-Seq) enable the most detailed view on
      transcriptomes offering an unmatched comprehensiveness and single-base
      resolution. Whole transcriptome data obtained by RNA-Seq can be used to detect
      and characterize all transcript species, including small RNAs. Here, we describe
      an RNA-Seq approach for comprehensive detection and characterization of small
      RNAs from Corynebacterium glutamicum, an actinobacterium of high industrial
      relevance and model organism for medically important Corynebacterianeae, such as
      C. diphtheriae and Mycobacterium tuberculosis. RESULTS: In our RNA-Seq approach,
      total RNA from C. glutamicum ATCC 13032 was prepared from cultures grown in
      minimal medium at exponential growth or challenged by physical (heat shock, cold
      shock) or by chemical stresses (diamide, H2O2, NaCl) at this time point. Total
      RNA samples were pooled and sequencing libraries were prepared from the isolated
      small RNA fraction. High throughput short read sequencing and mapping yielded
      over 800 sRNA genes. By determining their 5'- and 3'-ends and inspection of their
      locations, these potential sRNA genes were classified into UTRs of mRNAs (316),
      cis-antisense sRNAs (543), and trans-encoded sRNAs (262). For 77 of trans-encoded
      sRNAs significant sequence and secondary structure conservation was found by a
      computational approach using a whole genome alignment with the closely related
      species C. efficiens YS-314 and C. diphtheriae NCTC 13129. Three selected trans
      encoded sRNAs were characterized by Northern blot analysis and stress-specific
      transcript patterns were found. CONCLUSIONS: The study showed comparable numbers
      of sRNAs known from genome-wide surveys in other bacteria. In detail, our results
      give deep insight into the comprehensive equipment of sRNAs in C. glutamicum and
      provide a sound basis for further studies concerning the functions of these
      sRNAs.

PMID- 24138341
TI  - Treating pain in addicted patients: recommendations from an expert panel.
AB  - Clinicians may face pragmatic, ethical, and legal issues when treating addicted
      patients. Equal pressures exist for clinicians to always address the health care
      needs of these patients in addition to their addiction. Although controversial,
      mainly because of the lack of evidence regarding their long-term efficacy, the
      use of opioids for the treatment of chronic pain management is widespread. Their
      use for pain management in the addicted population can present even more
      challenges, especially when evaluating the likelihood of drug-seeking behavior.
      As the misuse and abuse of opioids continues to burgeon, clinicians must be
      particularly vigilant when prescribing chronic opioid therapy. The purpose of
      this article is to summarize recommendations from a recent meeting of experts
      convened to recommend how primary care physicians should approach treatment of
      chronic pain for addicted patients when an addiction specialist is not available
      for a referral. As there is a significant gap in guidelines and recommendations
      in this specific area of care, this article serves to create a foundation for
      expanding chronic pain guidelines in the area of treating the addicted
      population. This summary is designed to be a practical how-to guide for primary
      care physicians, discussing risk assessment, patient stratification, and
      recommended therapeutic approaches.

PMID- 24138343
TI  - The effect of ionic liquid hydrophobicity and solvent miscibility on pluronic
      amphiphile self-assembly.
AB  - The phase behavior of the triblock copolymer, (EO)20(PO)70(EO)20 (P123), in the
      water-immiscible (hydrophobic) ionic liquids (ILs), 1-butyl-3-methylimidazolium
      hexafluorophosphate (bmimPF6), and tris(pentafluoroethyl)trifluorophosphate
      (bmimFAP), has been investigated, and its amphiphilic self-assembly examined
      using small-angle X-ray scattering. The results obtained are contrasted with
      those for P123 in water. Direct and water-swellable micellar, hexagonal, and
      lamellar phases of P123 are found in bmimPF6, which behaves like a polar solvent
      despite being water immiscible, but bmimFAP behaves as a truly hydrophobic
      solvent, forming only a lamellar phase over a narrow composition range. The
      miscibility of bmimPF6 and water is increased by P123 addition, and at
      sufficiently high P123 concentrations, a single lamellar phase forms in which
      bmimPF6 and water are miscible in all proportions. In contrast, the preferential
      solubilization of bmimPF6 by PEO chains and bmimFAP by PPO chains causes the
      nanosegregation of these miscible ILs in concentrated P123 solutions. This leads
      to the formation of a P123/bmimPF6/bmimFAP microemulsion where bmimPF6 is the
      polar solvent and bmimFAP is the non-polar solvent. 

PMID- 24138342
TI  - Fabrication and evaluation of PLLA multichannel conduits with nanofibrous
      microstructure for the differentiation of NSCs in vitro.
AB  - Nerve conduits (NCs) with multiple longitudinally aligned channels, being
      mimicking the natural nerves anatomical structure, have been attracted more and
      more attentions. However, some specific structural parameters of a conduit that
      would be beneficial for further improvement of neural tissue regeneration were
      not comprehensively considered. Using a systematized device and combining low
      pressure injection molding and thermal-induced phase separation, we fabricated 33
      channel NCs (outer diameter 3.5 mm, channel diameter 200 MUm) with different well
      defined microscopic features, including NCs with a nano-fibrous microstructure
      (NNC), NCs with microspherical pores and nano-fibrous pore walls (MNC), and NCs
      with a ladder-like microstructure (LNC). The porosities of these NCs were ~90%
      and were independent of the fine microstructures, whereas the pore size
      distributions were clearly distinct. The adsorption of bovine serum albumin for
      the NNC was a result of having the highest specific surface area, which was 3.5
      times that of the LNC. But the mechanical strength of NNC was lower than that of
      two groups because of a relative high crystallinity and brittle characteristics.
      In vitro nerve stem cells (NSCs) incubation revealed that 14 days after seeding
      the NSCs, 31.32% cells were Map2 positive in the NNC group, as opposed to 15.76%
      in the LNC group and 23.29% in the MNC group. Addition of NGF into the culture
      medium, being distinctive specific surface area and a high adsorption of proteon
      for NNC, 81.11% of neurons derived from the differentiation of the seeded NSCs
      was obtained. As a result of imitating the physical structure of the basement
      membrane of the neural matrix, the nanofibrous structure of the NCs has
      facilitated the differentiation of NSCs into neurons. 

PMID- 24138344
TI  - Comparisons of patient satisfaction levels with complete dentures of different
      occlusions: a randomized clinical trial.
AB  - PURPOSE: There is a lack of evidence to recommend a particular type of posterior
      occlusal form for conventional complete dentures. The type of posterior occlusal
      scheme can affect complete denture stability, retention, and patient
      satisfaction. The objective of this study was to compare patient satisfaction to
      three types of complete denture occlusion using a randomized, crossover
      controlled trial. MATERIALS AND METHODS: Three sets of complete dentures were
      made for each of 15 patients (mean age = 58.87 +/- 15.02 years). They received
      (1) fully bilateral balanced occlusion (BBO), (2) lingualized occlusion, and (3)
      buccalized occlusion (BO) denture sets in random order. After wearing each set
      for 6 weeks, patient satisfaction was assessed using a 19-item version of the
      Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT). Each question
      was scored on a 1 to 5 scale for patients' problems with dentures (for these
      ordinal variables, 1 = "never" and 5 = "very often"). These items were first
      analyzed by Friedman tests and then by Wilcoxon rank tests for 80% test power at
      the 0.05-alpha level (d = 0.7). RESULTS: BO resulted in lower avoidance of
      particular foods and physical disability scores than fully BBO. CONCLUSIONS: With
      the caution of small sample size, the results of this study provide evidence that
      use of BO can improve food avoidance and physical disability aspects of patient
      satisfaction with complete dentures.

PMID- 24138345
TI  - Evaluating the Wellness School Assessment Tool for use in public health practice
      to improve school nutrition and physical education policies in New York.
AB  - BACKGROUND: Addressing the limitations of existing Local Wellness Policies (LWPs)
      and promoting their implementation remain priorities for health and education
      agencies. One gap has been the absence of a standard assessment to support LWP
      revision. During planning for an initiative to improve school nutrition and
      physical education policy, the Wellness School Assessment Tool (WellSAT) was
      evaluated. METHODS: Five public health practitioners used WellSAT to assess 50
      LWPs. A randomized, counterbalanced design ensured each LWP was coded twice by
      separate raters. Models evaluated the extent to which WellSAT ratings reflected
      differences in the LWPs and order, familiarity and rater effects. During field
      testing, 18 public health practitioners used WellSAT as part of a statewide
      public health initiative. RESULTS: In pilot testing the majority of the
      variability in WellSAT scores (median = 88%; range = 76% to 100%) was
      attributable to differences between policies. Correlations between independent
      raters' strength and comprehensiveness scores were strong, r = .88 and r = .77,
      respectively. During field testing, WellSAT was well accepted by public health
      practitioners and members of the school community. CONCLUSIONS: WellSAT
      represents a reliable and feasible tool for health and education agencies to use
      in improving LWPs and aligning them with recognized standards.

PMID- 24138346
TI  - School-based health promotion intervention: parent and school staff perspectives.
AB  - BACKGROUND: The prevalence of childhood obesity is high, particularly among
      minority youth. The objective of this article was to evaluate parent and school
      staff perspectives of childhood health and weight qualitatively to guide the
      development of a school-based obesity prevention program for minority youth.
      METHODS: Hispanic parents (N = 9) of first graders participated in 1 of 3 focus
      groups, consisting of 3 parents each. School staff (N = 7) participated in 1
      focus group. All sessions were digitally recorded and transcribed verbatim. Using
      NVivo, 2 independent coders rated the transcriptions to identify themes and a
      third coder addressed commonalities and discrepancies in the coding schemes.
      RESULTS: Parents and school staff have conflicting views over whose
      responsibility it is to provide nutritional education and participation in
      physical activity (PA). Parents felt the school should teach children about
      healthy nutrition, provide guidance in the cafeteria, and offer more structured
      PA in school. In contrast, school staff noted that parents have the primary
      responsibility of ensuring children get adequate nutrition and PA. CONCLUSIONS:
      Despite contrasting views, parents and staff agreed with the need for
      comprehensive school-based obesity prevention efforts emphasizing parent and
      teacher collaboration to promote healthy school and home environments.

PMID- 24138347
TI  - Using social-emotional and character development to improve academic outcomes: a
      matched-pair, cluster-randomized controlled trial in low-income, urban schools.
AB  - BACKGROUND: School-based social-emotional and character development (SECD)
      programs can influence not only SECD but also academic-related outcomes. This
      study evaluated the impact of one SECD program, Positive Action (PA), on
      educational outcomes among low-income, urban youth. METHODS: The longitudinal
      study used a matched-pair, cluster-randomized controlled design. Student-reported
      disaffection with learning and academic grades, and teacher ratings of academic
      ability and motivation were assessed for a cohort followed from grades 3 to 8.
      Aggregate school records were used to assess standardized test performance (for
      entire school, cohort, and demographic subgroups) and absenteeism (entire
      school). Multilevel growth-curve analyses tested program effects. RESULTS: PA
      significantly improved growth in academic motivation and mitigated disaffection
      with learning. There was a positive impact of PA on absenteeism and marginally
      significant impact on math performance of all students. There were favorable
      program effects on reading for African American boys and cohort students
      transitioning between grades 7 and 8, and on math for girls and low-income
      students. CONCLUSIONS: A school-based SECD program was found to influence
      academic outcomes among students living in low-income, urban communities. Future
      research should examine mechanisms by which changes in SECD influence changes in
      academic outcomes.

PMID- 24138348
TI  - Effectiveness of the energize elementary school program to improve diet and
      exercise.
AB  - BACKGROUND: The rate of childhood obesity has more than tripled during the past
      30 years. Research shows that prevention at an early age is more effective than
      treatment later in life. Energize is a multicomponent intervention incorporated
      into the school day that combines nutrition education and physical activity aimed
      at maintaining healthy weight among elementary school youth. This study evaluated
      the effectiveness of the Energize program for changing dietary and physical
      activity habits compared to a control group of children not participating in the
      program. METHODS: A total of 104, 3rd and 4th graders in 3 southern Indiana
      elementary schools took part in the study. A quasi-experimental design was used
      to assess dietary and exercise habits of students in Energize and control groups
      through 12-week diet/activity logs and post-test questionnaires after controlling
      for the pre-test results. RESULTS: Energize reduced consumption of French fries
      and potato chips, but did not increase physical activity. CONCLUSIONS: This study
      provides future researchers with a foundation for preparing longer studies of
      Energize or to compare multiple years of a standardized Energize curriculum.

PMID- 24138349
TI  - Abstinence-related word associations and definitions of abstinence and virginity
      among missouri high school freshmen.
AB  - BACKGROUND: The ways in which adolescents define and view sex, abstinence, and
      virginity impact the efforts of sexuality educators and sexual health
      professionals. This study examined terminology used by nonsexually active high
      school students to define abstinence and virginity and identified words students
      associate with these terms. Purposes included (1) describing words/phrases
      associated with abstinence; (2) describing phrases for "being abstinent until
      marriage" and "being a virgin;" (3) assessing concordance between word dyads
      associated with abstinence; and (4) assessing concordance between phrases
      defining "abstinent until marriage" and "a virgin." METHODS: In this study, 216
      freshmen provided information about beliefs, behaviors, and perceptions. Pearson
      chi-square tests and Wilcoxon sign-rank tests assessed sex-based differences,
      definitions, and levels of concordance were conducted. RESULTS: Girls' friends
      took an abstinence pledge (p = .004) and their parents (p = .025) and best
      friends (p < .001) think they should abstain. Male counterparts reported being
      dissatisfied with current sex status (p = .002) and high acceptance of sex before
      marriage (p = .011). Boys were more likely to endorse "negative" words than
      girls. CONCLUSIONS: Professionals need to use relevant materials incorporating
      terminology that resonates with adolescents and programs that engage coherent
      participant discussions.

PMID- 24138350
TI  - Does a socio-ecological school model promote resilience in primary schools?
AB  - BACKGROUND: This research investigates the extent to which the holistic,
      multistrategy "health-promoting school" (HPS) model using a resilience
      intervention can lead to improved resilience among students. METHODS: A quasi
      experimental design using a study cohort selected from 20 primary schools in
      Queensland, Australia was employed. Ten intervention schools using HPS protocols,
      with training support, were compared with 10 control schools in student
      resilience scores and protective factors. Baseline data explored the interactive
      effect of protective factors on overall resilience scores. Postintervention
      analysis compared changes in protective factors and resilience, after
      implementing the HPS project. RESULTS: Baseline data analysis indicated no
      significant differences in the mean scores of protective factors and resilience
      scores between intervention and control groups (except for school connection).
      After 18 months of implementation, a resurvey showed that the intervention group
      had significantly higher scores than the control group on students' family
      connection, community connection, peer support, and their overall resilience.
      CONCLUSIONS: Results showed that students in the HPS group had significantly
      higher scores on resilience than did students in the control group. A
      comprehensive, whole-school approach to building resilience that integrates
      students, staff, and community can strengthen important protective factors and
      build student resilience.

PMID- 24138351
TI  - Waist-to-height ratio and body mass index as indicators of cardiovascular risk in
      youth.
AB  - BACKGROUND: The purpose of this investigation was to determine if waist-to-height
      ratio (WHTR) or body mass index (BMI) is the better indicator of cardiovascular
      disease risk in children and adolescents of varying ages. METHODS: Data from
      children and adolescents (N = 2300) who were part of the 2003-2004 National
      Health and Nutrition Examination Survey (NHANES) were analyzed. Chi-square
      analyses (2 * 2) were used to compare risk levels of WHTR (>0.50) and BMI (>85th
      percentile) to systolic blood pressure (SBP) (>90th percentile) as well as total
      cholesterol (TC) (>200 mg(.) dL(-1) ) for the entire cohort and specified age
      groups. RESULTS: Significant relationships were detected between SBP and WHTR and
      BMI, respectively, for the entire cohort as well as the 2 oldest subsamples. A
      significant association was also noted for both WHTR and BMI to TC for the entire
      sample and the eldest age group. CONCLUSIONS: A significant association was
      observed between indicators of cardiovascular health risk and both WHTR and BMI
      in the entire NHANES cohort of boys and girls as well as in the older age groups.
      The younger groups of participants did not display a notable link between these
      cardiovascular indicators and WHTR or BMI.

PMID- 24138352
TI  - Family homework and school-based sex education: delaying early adolescents'
      sexual behavior.
AB  - BACKGROUND: Early sexual activity can undermine adolescents' future school
      success and health outcomes. The purpose of this study was to assess the role of
      a family homework component of a comprehensive sex education intervention in
      delaying sexual initiation for early adolescents and to explore what social and
      contextual factors prevent adolescents from completing these family homework
      activities. METHODS: This mixed methods study included 6th- and 7th-grade survey
      responses from 706 students at 11 middle school schools receiving a sex education
      intervention, as well as interviews from a subset of 33, 7th-grade students from
      the larger sample. RESULTS: Adolescents who completed more family homework
      assignments were less likely to have vaginal intercourse in 7th grade than those
      who completed fewer assignments, after controlling for self-reports of having had
      vaginal intercourse in 6th grade and demographic variables. Participants'
      explanations for not completing assignments included personal, curriculum, and
      family-based reasons. CONCLUSIONS: Family homework activities designed to
      increase family communication about sexual issues can delay sex among early
      adolescents and contribute to school-based sex education programs. Successful sex
      education programs must identify and address barriers to family homework
      completion.

PMID- 24138353
TI  - Sports game play: a comparison of moderate to vigorous physical activities in
      adolescents.
AB  - BACKGROUND: Research suggests participation in sports is an important contributor
      to overall adolescent physical activity (PA). Sports play has become increasingly
      important in physical education (PE) classes as a means for promoting healthful
      and enjoyable PA. Research is needed that investigates physiological and
      perceptual responses to sport play. METHODS: We studied 101 (55 males; 46
      females, age 11-14) students who participated in flag football (FF), basketball
      (BB), and flag rugby (FR). Activity counts were collected using accelerometers.
      Perceived competence and enjoyment were measured using the intrinsic motivation
      inventory. RESULTS: Each sport activity produced acceptable levels of activity
      and positive perceptual responses, but differences among sports were noted.
      Accelerometry data indicated that FR and BB were more intense than FF (p < .001).
      Perceptual data indicated participation in FR elicited higher perceptions of
      competence and greater enjoyment when compared to FF and BB (p < .001).
      CONCLUSIONS: Participation in sport activity within middle school PE classes
      provides excellent opportunities for energy expenditure and positive perceptual
      responses. Most importantly, FR provides an activity stimulus that has potential
      benefits both physiologically and psychologically.

PMID- 24138354
TI  - Evaluation of school tobacco-free policies in a rural Northern Plains state.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) has called for
      tobacco-free school (TFS) policies. In South Dakota (SD), a rural state with a
      large American Indian population, collaboration between state agencies focused on
      development and dissemination of a model TFS policy in 2008. This study explored
      the current status of TFS policies in statewide SD school districts. METHODS:
      Tobacco policies were requested from all SD school district administrators. A 26
      point checklist based on CDC TFS policy guidelines was used to evaluate policies.
      Follow-up interviews were conducted with selected superintendents. RESULTS:
      Policies were received from 144 of 217 districts (66% response). Participation
      was higher for public districts than tribal/Bureau of Indian Education (BIE)
      districts and nonpublic districts. The overall mean policy score was 11.6 (SD
      5.1). Public school districts had the highest mean (12.3) followed by nonpublic
      (8.9) and tribal/BIE (7.5). In a subset of districts with a large American Indian
      population (>30%), policy scores were lower for those located on reservation or
      tribal lands compared with other locations. Barriers to policy development were
      identified as time and staff expertise. CONCLUSIONS: There is a need to improve
      statewide TFS policies. A district report card with recommendations for
      improvement and a resource guide were developed and disseminated.

PMID- 24138356
TI  - Providing Culturally Congruent Care for Saudi Patients and their Families.
AB  - Abstract This article aims to increase an awareness of caring for Saudi families
      by non-Saudi nurses to improve their understanding of culturally competent care
      from a Saudi perspective. Healthcare providers have a duty of a care to deliver
      holistic and culturally specific health care to their patients. As a consequence
      of 'duty of care' obligations, healthcare providers must facilitate culturally
      congruent care for patients of diverse cultural backgrounds. For the Saudi family
      considerable cultural clashes may arise when Saudi patients are hospitalised and
      receive care from healthcare professionals who do not understand Islamic
      principles and Saudi cultural beliefs and values. The healthcare workforce in
      Saudi Arabia is a unique multicultural workforce that is mix of Saudi and
      significant other nationalities. Saudi nurses for example represent only 36.3% of
      the workforce in the different health sectors. Whilst the different ethnic and
      cultural background expatriate nurses represent 63.7% (Ministry of Health, 2010).
      This article also could increase the awareness of healthcare professionals caring
      for Arab and Muslims patients in another context in the world.

PMID- 24138355
TI  - Primary care obesity management in Hungary: evaluation of the knowledge, practice
      and attitudes of family physicians.
AB  - BACKGROUND: Obesity, a threatening pandemic, has an important public health
      implication. Before proper medication is available, primary care providers will
      have a distinguished role in prevention and management. Their performance may be
      influenced by many factors but their personal motivation is still an under
      researched area. METHODS: The knowledge, attitudes and practice were reviewed in
      this questionnaire study involving a representative sample of 10% of all
      Hungarian family physicians. In different settings, 521 practitioners (448 GPs
      and 73 residents/vocational trainees) were questioned using a validated
      questionnaire. RESULTS: The knowledge about multimorbidity, a main consequence of
      obesity was balanced.Only 51% of the GPs were aware of the diagnostic threshold
      for obesity; awareness being higher in cities (60%) and the highest among
      residents (90%). They also considered obesity an illness rather than an aesthetic
      issue.There were wider differences regarding attitudes and practice, influenced
      by the the doctors' age, gender, known BMI, previous qualification, less by
      working location.GPs with qualification in family medicine alone considered
      obesity management as higher professional satisfaction, compared to physicians
      who had previously other board qualification (77% vs 68%). They measured their
      patients' waist circumference and waist/hip ratio (72% vs 62%) more frequently,
      provided the obese with dietary advice more often, while this service was less
      frequent among capital-based doctors who accepted the self-reported body weight
      dates by patients more commonly. Similar reduced activity and weight-measurement
      in outdoor clothing were more typical among older doctors.Diagnosis based on BMI
      alone was the highest in cities (85%). Consultations were significantly shorter
      in practices with a higher number of enrolled patients and were longer by female
      providers who consulted longer with patients about the suspected causes of
      developing obesity (65% vs 44%) and offered dietary records for patients
      significantly more frequently (65% vs 52%). Most of the younger doctors agreed
      that obesity management was a primary care issue.Doctors in the normal BMI range
      were unanimous that they should be a model for their patients (94% vs 81%).
      CONCLUSION: More education of primary care physicians, available practical
      guidelines and higher community involvement are needed to improve the obesity
      management in Hungary.

PMID- 24138357
TI  - Sleep loss and sleep disorders.

PMID- 24138358
TI  - Public health implications of sleep loss: the community burden.
AB  - Poor sleep imparts a significant personal and societal burden. Therefore, it is
      important to have accurate estimates of its causes, prevalence and costs to
      inform health policy. A recent evaluation of the sleep habits of Australians
      demonstrates that frequent (daily or near daily) sleep difficulties (initiating
      and maintaining sleep, and experiencing inadequate sleep), daytime fatigue,
      sleepiness and irritability are highly prevalent (20%-35%). These difficulties
      are generally more prevalent among females, with the exception of snoring and
      related difficulties. While about half of these problems are likely to be
      attributable to specific sleep disorders, the balance appears attributable to
      poor sleep habits or choices to limit sleep opportunity. Study of the economic
      impact of sleep disorders demonstrates financial costs to Australia of $5.1
      billion per year. This comprises $270 million for health care costs for the
      conditions themselves, $540 million for care of associated medical conditions
      attributable to sleep disorders, and about $4.3 billion largely attributable to
      associated productivity losses and non-medical costs resulting from sleep loss
      related accidents. Loss of life quality added a substantial further non-financial
      cost. While large, these costs were for sleep disorders alone. Additional costs
      relating to inadequate sleep from poor sleep habits in people without sleep
      disorders were not considered. Based on the high prevalence of such problems and
      the known impacts of sleep loss in all its forms on health, productivity and
      safety, it is likely that these poor sleep habits would add substantially to the
      costs from sleep disorders alone.

PMID- 24138359
TI  - Sleep loss and circadian disruption in shift work: health burden and management.
AB  - About 1.5 million Australians are shift workers. Shift work is associated with
      adverse health, safety and performance outcomes. Circadian rhythm misalignment,
      inadequate and poor-quality sleep, and sleep disorders such as sleep apnoea,
      insomnia and shift work disorder (excessive sleepiness and/or insomnia temporally
      associated with the work schedule) contribute to these associations. Falling
      asleep at work at least once a week occurs in 32%-36% of shift workers. Risk of
      occupational accidents is at least 60% higher for non-day shift workers. Shift
      workers also have higher rates of cardiometabolic diseases and mood disturbances.
      Road and workplace accidents related to excessive sleepiness, to which shift work
      is a significant contributor, are estimated to cost $71-$93 billion per annum in
      the United States. There is growing evidence that understanding the
      interindividual variability in sleep-wake responses to shift work will help
      detect and manage workers vulnerable to the health consequences of shift work. A
      range of approaches can be used to enhance alertness in shift workers, including
      screening and treating sleep disorders, melatonin treatment to promote sleep
      during the daytime, and avoidance of inappropriate use of sedatives and
      wakefulness-promoters such as modafinil and caffeine. Short naps, which minimise
      sleep inertia, are generally effective. Shifting the circadian pacemaker with
      appropriately timed melatonin and/or bright light may be used to facilitate
      adjustment to a shift work schedule in some situations, such as a long sequence
      of night work. It is important to manage the health risk of shift workers by
      minimising vascular risk factors through dietary and other lifestyle approaches.

PMID- 24138360
TI  - Circadian rhythm disorders among adolescents: assessment and treatment options.
AB  - Delayed sleep phase disorder (DSPD) - a circadian rhythm sleep disorder - is most
      commonly seen in adolescents. The differential diagnosis between DSPD and
      conventional psychophysiological insomnia is important for correct therapeutic
      intervention. Adolescent DSPD sleep duration is commonly 9 hours or more.
      Depression may be comorbid with DSPD. DSPD has a negative impact on adolescent
      academic performance. DSPD treatments include bright light therapy,
      chronotherapeutic regimens, and administration of melatonin as a chronobiotic (as
      distinct from a soporific). Attention to non-photic and extrinsic factors
      including healthy sleep parameters is also important to enable better sleep and
      mood outcomes in adolescents.

PMID- 24138361
TI  - How to assess, diagnose, refer and treat adult obstructive sleep apnoea: a
      commentary on the choices.
AB  - Obstructive sleep apnoea (OSA) determined by polysomnography is highly prevalent,
      affecting about 25% of men and 10% of women in the United States, although most
      have few or no symptoms. Symptomatic moderate to severe OSA has major health
      implications related to daytime sleepiness, such as increased accidents, altered
      mood and loss of productivity in the workplace. Severe OSA may increase the risk
      of cardiovascular disease independent of daytime sleepiness. A major challenge is
      to correctly identify, from the large community pool of disease, people with
      symptoms and those at risk of long-term complications. For treatment plans to
      achieve quality patient outcomes, clinicians must have a clear understanding of
      patients' symptoms and their motivations for presentation, and be knowledgeable
      about the evidence surrounding the health risks of OSA and the relative merits of
      the various diagnostic and treatment options available. The diagnosis of OSA
      represents a teachable moment to target adverse lifestyle factors such as
      excessive weight, excessive alcohol consumption and smoking, which may be
      contributing to OSA and long-term cardiometabolic risk. OSA assessment and
      management has traditionally involved specialist referral and in-laboratory
      polysomnography. However, these services may not always be easy to access.
      Controlled studies have shown that patients with a high pretest probability of
      symptomatic, moderate to severe OSA can be managed well in primary care, or by
      skilled nurses with appropriate medical backup, using simplified ambulatory
      models of care. The future of sleep apnoea assessment and management will likely
      include models of care that involve early referral to specialists of patients
      with complex or atypical presentations, and an upskilled and supported primary
      care workforce to manage symptomatic, uncomplicated, high pretest probability
      disease.

PMID- 24138362
TI  - Impact of obstructive sleep apnoea on diabetes and cardiovascular disease.
AB  - Obstructive sleep apnoea (OSA) is a potential cause of systemic hypertension in
      young and middle-aged people, and treatment helps reduce blood pressure in some
      patients. Severe OSA (apnoea-hypopnoea index [AHI] > 30/h) is strongly associated
      with increased mortality, stroke and cardiovascular disease in middle-aged
      populations. The cardiovascular risk from moderate OSA (AHI, 15-30/h) is
      uncertain, particularly if the oxygen desaturation index is low, although the
      data suggest an increased risk for stroke (particularly in men). There is no
      evidence of increased cardiovascular risk from mild OSA (AHI < 15/h). In the
      elderly, the cardiovascular risks of OSA are uncertain, although there is a
      likelihood of increased risk of stroke. Current, ongoing randomised controlled
      trials will inform whether OSA is a reversible cardiovascular risk factor within
      the next 5 years. Patients with cardiovascular disease, stroke, diabetes, obesity
      or poorly controlled hypertension are at high risk of OSA and should be
      questioned for symptoms of OSA, which, if present, may warrant further
      investigation and treatment. Weight loss has an unpredictable effect on OSA
      severity, but is independently beneficial for symptoms and metabolic health in
      OSA patients and is recommended for all overweight and obese OSA patients.

PMID- 24138363
TI  - Sleep disorders in children.
AB  - Sleep disorders are very common in childhood and are often amenable to simple
      advice and parental education. Questions about sleep should be an integral part
      of every paediatric consultation. Children with underlying syndromes or complex
      medical conditions often have multiple sleep issues. Excessive sleepiness in
      children requires careful history-taking and consideration of specialised
      investigation. Obstructive sleep apnoea (OSA) is a common condition in childhood
      with important health implications. The high prevalence of OSA warrants rigorous
      attempts to identify children at higher risk and manage them appropriately.
      Adenotonsillectomy is a highly efficacious therapy for paediatric OSA. A current
      major issue is to improve ways of distinguishing mild from severe OSA before a
      child undergoes adenotonsillectomy, as those with more severe disease are at
      increased risk of postoperative complications and should undergo
      adenotonsillectomy in a tertiary centre. Children with obesity and other comorbid
      conditions are at increased risk of persisting OSA despite adenotonsillectomy.
      Topical (nasal) steroids and/or anti-inflammatory agents have a role in the non
      surgical treatment of mild OSA. Continuous positive airway pressure and
      orthodontic interventions are treatment options for treatment of persisting OSA
      in children. 

PMID- 24138364
TI  - Insomnia: prevalence, consequences and effective treatment.
AB  - Insomnia is common and can have serious consequences, such as increased risk of
      depression and hypertension. Acute and chronic insomnia require different
      management approaches. >Chronic insomnia is unlikely to spontaneously remit, and
      over time will be characterised by cycles of relapse and remission or persistent
      symptoms. Chronic insomnia is best managed using non-drug strategies such as
      cognitive behaviour therapy. For patients with ongoing symptoms, there may be a
      role for adjunctive use of medications such as hypnotics. 

PMID- 24138365
TI  - Saints preserve us from food folly.

PMID- 24138366
TI  - Patient safety in hospitals - can we measure it?

PMID- 24138367
TI  - Head injury prevention for bicyclists - helmets make a difference.

PMID- 24138368
TI  - Crohn's disease: towards improving postsurgical outcomes.

PMID- 24138370
TI  - Preventing mental disorders: the time is right.

PMID- 24138371
TI  - The dark side to Halloween: marketing unhealthy products to our children?

PMID- 24138372
TI  - Australia's servicewomen and female veterans: do we understand their health
      needs?

PMID- 24138373
TI  - Removing the GST exemption for fresh fruits and vegetables could cost lives.

PMID- 24138374
TI  - Suicide risk assessment: where are we now?

PMID- 24138375
TI  - Suicide risk assessment: where are we now?

PMID- 24138376
TI  - Updated Creutzfeldt-Jakob disease infection control guidelines: sifting facts
      from fiction.

PMID- 24138377
TI  - Updated Creutzfeldt-Jakob disease infection control guidelines: sifting facts
      from fiction.

PMID- 24138378
TI  - The impact of checking the Australian Organ Donor Register on family consent
      rates.

PMID- 24138379
TI  - The Western Australian Audit of Surgical Mortality: outcomes from the first 10
      years.
AB  - The Western Australian Audit of Surgical Mortality (WAASM) is an external, peer
      reviewed audit of all deaths that occur in hospital of patients under the care of
      a surgeon. We conducted a retrospective analysis of prospective audit data
      collected from 1 January 2002 to 31 December 2011. The annual number of deaths
      peaked in 2006, then fell 22% by 2011. After correcting for population growth,
      the overall reduction from 2002 to 2011 was 30% (regression analysis, P = 0.002).
      Some changes in practice, such as with pancreatic surgery, can be directly
      attributed to WAASM. There is strong evidence to suggest that WAASM improved
      other aspects of care, such as thromboembolic prophylaxis, consultant supervision
      and fluid management. A shift of high-risk patients to teaching hospitals, where
      there is a greater ability to "rescue" patients after complications, may have
      been an important factor in improved outcomes. This external, peer-reviewed
      mortality audit has changed surgical practice and reduced deaths. The same
      process should be applied to other sentinel events, and the lessons learned can
      also be extended to non-surgical specialties.

PMID- 24138380
TI  - Measuring the incidence of hospital-acquired complications and their effect on
      length of stay using CHADx.
AB  - OBJECTIVES: To use an automated Classification of Hospital Acquired Diagnoses
      (CHADx) reporting system to report the incidence of hospital-acquired
      complications in inpatients and investigate the association between hospital
      acquired complications and hospital length of stay (LOS) in multiday-stay
      patients. DESIGN: Retrospective cross-sectional study for calendar years 2010 and
      2011. SETTING: South Metropolitan Health Service in Western Australia, which
      consists of two teaching and three non-teaching hospitals. MAIN OUTCOME MEASURES:
      Incidence of hospital-acquired complications and mean LOS for multiday-stay
      patients. RESULTS: Of 436 841 inpatient separations, 29 172 (6.68%) had at least
      one hospital-acquired complication code assigned in the administrative data, and
      there were a total of 56 326 complication codes. The three most common
      complications were postprocedural complications; cardiovascular complications;
      and labour, delivery and postpartum complications. In the subset of data on
      multiday-stay patients, crude mean LOS was longer in separations for patients
      with hospital-acquired complications than in separations for those without such
      complications (17.4 days v 5.4 days). After adjusting for potential confounders,
      separations for patients with hospital-acquired complications had almost four
      times the mean LOS of separations for those without such complications (incident
      rate ratio, 3.84; 95% CI, 3.73-3.96; P < 0.001). CONCLUSIONS: An automated CHADx
      reporting system can be used to collect data on patients with hospital-acquired
      complications. Such data can be used to increase emphasis on patient safety and
      quality of care and identify potential opportunities to reduce LOS.

PMID- 24138381
TI  - Global trends in testosterone prescribing, 2000-2011: expanding the spectrum of
      prescription drug misuse.
AB  - OBJECTIVE: To provide the first multinational survey of temporal trends in
      testosterone prescribing, given that anecdotal evidence indicates that it is
      increasing in some countries, including Australia. DESIGN: Sales data for all
      testosterone products were obtained for 41 countries for each year from 2000 to
      2011. For each testosterone product type (injectable, implantable, oral,
      transdermal), units sold were converted into defined monthly doses per year,
      reflecting total testosterone prescribing per product. MAIN OUTCOME MEASURES:
      National testosterone prescribing rate overall and per product type on a per
      capita basis. RESULTS: For every region and 37 of 41 countries, there was a major
      and progressive increase in defined monthly doses per year per capita over the 11
      years surveyed. In most countries, the increases were steeper for the last half
      of the survey period. The proportion of testosterone prescribing represented by
      transdermal testosterone products, a surrogate measure of prescribing for older
      men, increased even more than did the total usage of testosterone products.
      CONCLUSIONS: In the absence of any new indications, off-label testosterone
      prescribing has increased in most countries in 2000-2011, especially over the
      last half of the period. The increased testosterone prescribing appears to be
      primarily for older men and driven by clinical guidelines that endorse
      testosterone prescribing for age-related functional androgen deficiency
      (andropause). By eliminating the fundamental distinction between pathological and
      functional androgen deficiency, these guidelines tacitly promote increased
      testosterone prescribing, bypassing the requirement for high-quality clinical
      evidence of safety and efficacy and creating dramatic increases in prescription
      of testosterone products.

PMID- 24138382
TI  - Summer of sorrow: measuring exposure to and impacts of trauma after Queensland's
      natural disasters of 2010-2011.
AB  - OBJECTIVES: To assess the population prevalence of property, income and emotional
      impacts of the 2010-2011 Queensland floods and cyclones. DESIGN, SETTING AND
      PARTICIPANTS: Cross-sectional telephone-based survey using a brief trauma
      exposure and impact screening instrument, conducted between 11 March and 6 June
      2011, of 6104 adults who answered natural disaster and mental health questions.
      MAIN OUTCOME MEASURES: Natural disaster property damage exposure and emotional
      wellbeing impacts. RESULTS: Two-thirds of respondents (62%) reported being
      affected by the disasters, with property damage exposure ranging from 37.2%
      (suburb or local area) to 9.2% (own home, with 2.1% living elsewhere at least
      temporarily). Income was reduced for 17.0% of respondents and 11.7% of income
      producing property owners reported damage to those properties. Trauma impacts
      ranged from 14.3% of respondents feeling "terrified, helpless or hopeless" to
      3.9% thinking they might be "badly injured or die". Up to 5 months after the
      disasters, 7.1% of respondents were "still distressed" and 8.6% were "worried
      about how they would manage". Adults of working age and residents of regional and
      remote areas and of socioeconomically disadvantaged areas were disproportionately
      likely to report exposure to damage and emotional impacts. CONCLUSIONS: Weather
      related disasters exact a large toll on the population through property damage
      and resultant emotional effects. Vulnerable subpopulations are more severely
      affected. There is a need for realistic, cost-effective and rapid-deployment mass
      interventions in the event of weather disasters.

PMID- 24138383
TI  - Primary amenorrhoea with hypertension: undiagnosed 17-alpha-hydroxylase
      deficiency.

PMID- 24138386
TI  - Delayed hysteroscopic resection of retained tissues and uterine conservation
      after conservative treatment for placenta accreta.
AB  - BACKGROUND: Conservative management of both the uterus and the abnormal placenta,
      which is left inside the uterus at the time of delivery, is one option of
      placenta accreta management. Complete elimination of the residual placenta is the
      main challenge of this procedure. AIM: To report the role, efficacy and safety of
      hysteroscopic resection in women presenting with severe pelvic pain and chronic
      intra-uterine retention after conservative treatment of placenta accreta.
      MATERIAL AND METHODS: Four consecutive women who were treated with hysteroscopic
      resection of retained tissues after conservative treatment of placenta accreta or
      percreta at the time of delivery. Clinical files and surgical procedures were
      reviewed. All procedures were performed because of chronic pelvic pain and the
      absence of a complete spontaneous placental elimination. RESULTS: All procedures
      were successful and uneventful. The uterus was conserved with a complete
      disappearance of the symptoms in the four women, and two of them became pregnant.
      CONCLUSION: Hysteroscopic resection seems effective and safe for shortening the
      duration of placental elimination after conservative treatment in women with
      severe pelvic pain due to uterine retention. This approach allows conserving the
      uterus and future fertility.

PMID- 24138387
TI  - Efficacy of various irrigation protocols on the removal of triple antibiotic
      paste.
AB  - AIM: To compare the efficacy of irrigation protocols on the removal of triple
      antibiotic paste (metronidazole, ciprofloxacin and minocycline) (TAP) from
      artificial grooves in root canals. METHODOLOGY: Root canals in 72 extracted
      single-rooted teeth were prepared using ProTaper rotary instruments up to size
      F5. The roots were split longitudinally and a standardized groove was prepared in
      the apical part of one segment. TAP was placed in the grooves, and the root
      halves were reassembled. The roots were randomly divided into six experimental
      groups according to the irrigation protocol used: distilled water, 1% NaOCl, 2.5%
      NaOCl, 100% ethanol, 17% EDTA and passive ultrasonic irrigation (PUI) with 1%
      NaOCl. The root segments were disassembled, and the amount of TAP remaining was
      evaluated under a stereomicroscope at 20* magnification using a four-grade
      scoring system. The data were evaluated statistically using Kruskal-Wallis and
      Mann-Whitney U-tests with a 95% confidence level (P = 0.05). RESULTS: There were
      significant differences amongst the groups (P < 0.001). Passive ultrasonic
      irrigation (PUI) with 1% NaOCl removed significantly more TAP than the other
      irrigating solutions (P < 0.05). Distilled water, 1% NaOCl, ethanol and EDTA were
      associated with significantly more remaining TAP. CONCLUSIONS: PUI with 1% NaOCl
      was more effective in removing TAP from artificial grooves in root canals than
      other irrigating solutions without ultrasonic agitation. It was not possible
      completely to remove TAP from root canals.

PMID- 24138388
TI  - Transcystic approach with micro-incision of the cystic duct and its confluence
      part in laparoscopic common bile duct exploration.
AB  - BACKGROUND: Laparoscopic transcystic common bile duct exploration has become a
      safe and ideal treatment of common bile duct stones. This study was designed to
      explore the clinical value of modified laparoscopic transcystic common bile duct
      exploration as a first line of treatment for patients with common bile duct
      stones. PATIENTS AND METHODS: A retrospective, case-control study of clinically
      comparable groups of patients who underwent the laparoscopic transcystic approach
      with micro-incision of the cystic duct and its confluence part in common bile
      duct exploration (LTM-CBD) (n=110) and laparoscopic common bile duct exploration
      (LCBD) (n=100) under the care of one surgeon was performed. All clinical data
      were analyzed retrospectively. RESULTS: There was no significant difference in
      terms of operation time between the two groups (P>.05). Postoperative hospital
      stay and abdominal drainage time were shorter in the LTM-CBD group than in the
      LCBD group (P<.05). Postoperative bile leakage was seen in 1 case (1 of 110) in
      the LTM-CBD group and 10 cases (10 of 100) in the LCBD group (P<.05). Twenty
      patients underwent T-tube drainage in the LCBD group, and primary closure was
      performed in the other patients; however, all cases in the LTM-CBD group
      underwent primary closure. The median follow-up was 12 months; 2 patients in the
      LCBD group who suffered from bile leakage presented with obstructive jaundice due
      to bile duct stenosis 6 months postoperatively. CONCLUSIONS: LTM-CBD, which can
      avoid postoperative T-tube drainage, decrease complications, shorten
      hospitalization time, and enhance the existing quality, is a minimally invasive,
      safe, and effective treatment.

PMID- 24138389
TI  - Inhibition of porcine endogenous retrovirus in PK15 cell line by efficient
      multitargeting RNA interference.
AB  - To effectively suppress porcine endogenous retroviruses (PERV)s, RNAi technique
      was utilized. RNAi is the up-to-date skill for gene knockdown which
      simultaneously multitargets both gag and pol genes critical for replication of
      PERVs. Previously, two of the most effective siRNAs (gag2, pol2) were found to
      reduce the expression of PERVs. Concurrent treatment of these two siRNAs
      (gag2+pol2) showed knockdown efficiency of up to 88% compared to negative
      control. However, despite the high initial knockdown efficiency 48 h after
      transfection caused by siRNA, it may only be a transient effect of suppressing
      PERVs. The multitargeting vector was designed, containing both gag and pol genes
      and making use of POL II miR Expression Vector, which allowed for persistent and
      multiple targeting. This is the latest shRNA system technique expressing and
      targeting like miRNA. Through antibiotics resistance characteristics utilizing
      this vector, miRNA-transfected PK15 cells (gag2-pol2) were selected during 10
      days. An 88.1% reduction in the level of mRNA expression was found. In addition,
      we performed RT-activity analysis and fluorescence in situ hybridization assay,
      and it demonstrated the highest knockdown efficiency in multitargeting
      (gag2+pol2) miRNA group. Therefore, according to the results above, gene
      knockdown system (siRNA and shRNA) through multitargeting strategy could
      effectively inhibit PERVs.

PMID- 24138390
TI  - Systematic review with network meta-analysis: pharmacological prophylaxis against
      post-ERCP pancreatitis.
AB  - BACKGROUND: The efficacy of many pharmacological agents for preventing post-ERCP
      pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but
      it is unclear which agent(s) should be used in clinical practice. Network meta
      analyses of RCTs are used to simultaneously compare several agents to determine
      their relative efficacy and identify priority agents for comparison in future
      RCTs. AIM: To evaluate pharmacological agents for the prevention of PEP by
      conducting a network meta-analysis of RCTs. METHODS: We searched MEDLINE, EMBASE
      and Cochrane Library databases for RCTs that evaluated the efficacy of agents for
      preventing PEP. RCTs were simultaneously analysed using random-effects network
      meta-analysis under the Bayesian framework to identify the best agents. The
      efficacy of agents was ordered according to the probability of being ranked as
      any of the top three best performing agents. RESULTS: The network meta-analysis
      included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine
      (adrenaline) was the most efficacious agent with 85.9% probability of ranking
      among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%)
      and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal
      NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving
      topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR
      0.25, 95% probability interval 0.06-0.66). CONCLUSIONS: Topical epinephrine and
      rectal NSAIDs are the most efficacious agents for preventing post-ERCP
      pancreatitis, based on existing RCTs. Combinations of these agents, which act on
      different steps in the pathogenesis of post-ERCP pancreatitis, should be
      evaluated in future trials.

PMID- 24138391
TI  - Congenital infantile fibrosarcoma of the lip.
AB  - Infantile congenital fibrosarcomas are rare neoplasms that usually present on the
      extremities, and although they are locally invasive, they rarely metastasize.
      They are commonly misdiagnosed as hemangiomas or other vascular tumors, so
      further evaluation by pathology is required for proper diagnosis. We describe a
      newborn with a neoplastic growth of the lower lip that was thought to be an
      infantile hemangioma that did not respond to therapy. When the child was 2 months
      old, an incisional biopsy demonstrated a fibrosarcoma. This case highlights
      congenital infantile fibrosarcoma as a mimic of infantile hemangioma. To our
      knowledge this is first case report of congenital infantile fibrosarcoma
      involving the lip.

PMID- 24138392
TI  - Curcumin up-regulates phosphatase and tensin homologue deleted on chromosome 10
      through microRNA-mediated control of DNA methylation--a novel mechanism
      suppressing liver fibrosis.
AB  - Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has been
      reported to play a role in the suppression of activated hepatic stellate cells
      (HSCs). Moreover, it has been demonstrated that hypermethylation of the PTEN
      promoter is responsible for the loss of PTEN expression during HSC activation.
      Methylation is now established as a fundamental regulator of gene transcription.
      MicroRNAs (miRNAs), which can control gene expression by binding to their target
      genes for degradation and/or translational repression, were found to be involved
      in liver fibrosis. However, the mechanism responsible for miRNA-mediated
      epigenetic regulation in liver fibrosis still remained unclear. In the present
      study, curcumin treatment significantly resulted in the inhibition of cell
      proliferation and an increase in the apoptosis rate through the up-regulation of
      PTEN associated with a decreased DNA methylation level. Only DNA
      methyltransferase 3b (DNMT3b) was reduced in vivo and in vitro after curcumin
      treatment. Further studies were performed aiming to confirm that the knockdown of
      DNMT3b enhanced the loss of PTEN methylation by curcumin. In addition, miR-29b
      was involved in the hypomethylation of PTEN by curcumin. MiR-29b not only was
      increased by curcumin in activated HSCs, but also was confirmed to target DNMT3b
      by luciferase activity assays. Curcumin-mediated PTEN up-regulation, DNMT3b down
      regulation and PTEN hypomethylation were all attenuated by miR-29b inhibitor.
      Collectively, it is demonstrated that curcumin can up-regulate miR-29b
      expression, resulting in DNMT3b down-regulation in HSCs and epigenetically
      regulated PTEN involved in the suppression of activated HSCs. These results
      indicate that miRNA-mediated epigenetic regulation may be a novel mechanism
      suppressing liver fibrosis. 

PMID- 24138393
TI  - Recent advances in protein-ligand interactions: molecular dynamics simulations
      and binding free energy.
AB  - Computational techniques are one of the most emerging topics in structural and
      molecular biology. Molecular dynamics (MD) simulations are used not only to
      explore the conformational aspects of biological systems but also to have
      significant scope in protein-ligand interactions. Then the binding free energy
      calculations are readily applied to the simulated systems in order to predict the
      binding affinities. The thermodynamic properties are directly related to protein
      ligand interactions which are dependent upon a few specific parameters. In the
      present review, we highlight some facts related to protein-ligand complexes, by
      starting with a survey of MD simulations and binding free energy calculations and
      ending with some successful implementations of these computational techniques. 

PMID- 24138394
TI  - A review of monoamine transporter-ligand interactions.
AB  - Transporters of the monoamines serotonin, dopamine, and norepinephrine are plasma
      membrane proteins belonging to the neurotransmitter sodium symporter family
      (NSS). Monoamine transporters (MATs) by facilitating reuptake of
      neurotransmitters from the synapse into the presynaptic nerve terminal, regulate
      neurotransmitter chemical signaling and maintain homeostasis. MATs are targets
      for several psychostimulants such as cocaine and amphetamine; and also for drugs
      treating several psychiatric disorders such as depression, attention deficit
      hyperactivity disorder, Parkinson's disease, and schizophrenia. Since, currently
      available treatment has several limitations and side effects, novel treatment is
      highly desired. Efforts to develop better treatment have been hampered by the
      lack of crystal structures for MATs. However, leucine transporter (LeuTAa), a
      bacterial protein from Aquifex aeolicus, belonging to the same NSS family as MATs
      has recently been crystallized. LeuTAa is used as a template to develop homology
      models of MATs, which facilitates understanding of the structure, function and
      pharmacology of MATs. Experimental methods for drug discovery demand a
      significant amount of time, effort and money. Efficient utilization of
      computational techniques hastens the process of drug discovery and also
      significantly reduces the cost. Assessing the binding affinity of drugs to the
      receptors is a key aspect of drug design. Free energy calculations compliment the
      experiment by quantitatively assessing the affinity of ligands to receptors.
      These methods are highly beneficial in the lead identification and optimization
      stages of rational drug design. We review the currently available free energy
      methods to treat protein-ligand interactions along with several free energy
      studies performed on MATs. 

PMID- 24138395
TI  - Applications of docking and molecular dynamics in drug design.

PMID- 24138396
TI  - Exploring the molecular mechanism of action between drug and RNA polymerase based
      on partially-resolved spatial structures.
AB  - The RNA polymerase of Influenza A virus (IAV), which is comprised of three units
      PA, PB1 and PB2, is involved in transcription and replication of the influenza
      virus. In order to develop effective treatment for IAV, researchers have focused
      on designing drugs targeting IAV polymerase. Currently, crystal structures of the
      IAV polymerase PA-PB1, PB1-PB2 complexes and the PA subunit have been obtained by
      several groups, providing useful information regarding potential binding sites in
      drug design. However, to gain full understanding of the molecular mechanism of
      IAV polymerase in viral transcription and replication, thereby aiding drug
      development, a complete atomistic structure of the RNA polymerase is required. In
      this paper, we employed computer-aided drug design tools to describe the complete
      structure of the RNA polymerase and proposed a putative mechanism. We predict
      that the combination of Vancomycin and Oseltamivir will be an effective drug to
      universally treat IAVs with no resultant drug resistance if this putative
      mechanism is true. 

PMID- 24138397
TI  - Drug design benefits from molecular dynamics: some examples.
AB  - With the increasing application of various computer techniques in new drug
      development, molecular dynamics (MD) simulation, as a promising tool for rational
      drug design, is playing a more and more vital role. In this review, we initially
      give a brief recapitulation of relevant basic MD theories, followed by an
      additional introduction of the current state-of-the-art MD methodologies, mainly
      involving steered molecular dynamics (SMD) and constant pH molecular dynamics
      (CpHMD). Both of the methods extend research field of conventional MD
      simulations. In the end, some interesting examples using these latest MD
      approaches are also presented to demonstrate their practicability and validity
      for the study on the ligand-receptor interaction. 

PMID- 24138398
TI  - Molecular properties prediction, docking studies, and antimicrobial screening of
      1,3,4-thiadiazole and s-triazole derivatives.
AB  - A series of 1,3,4-thiadiazoles and s-triazoles were subjected to Molinspiration,
      ALOGPS 2.1, and Osiris programs to predict their molecular properties that are
      important for drug candidates. Subsequently, all of them were docked into the
      active sites of enzymes namely glucosamine-6-phosphate synthase (GlcN-6-P), VIM-2
      metallo-beta- lactamase (VIM-2), chitinase A1 (ChiA1), and sterol 14 alpha
      demethylase (CYP51) that were considered in antimicrobial studies of thiadiazole
      and s-triazole derivatives. Since all compounds fulfilled the criteria for good
      membrane permeability, oral bioavailability, low toxicity and the potential
      inhibitory activities towards VIM-2, ChiA1, and CYP51, most of them were
      synthesized and their antimicrobial activity has been tested. 

PMID- 24138399
TI  - Docking and virtual screening to identify PKC agonists: potentials in anticancer
      therapeutics.
AB  - Protein kinase C (PKC) is down-stream to most of the G-protein coupled receptor
      or tyrosine kinase receptors mediated signaling events from the cell surface. PKC
      C1 domain has a hydrophobic region with a polar groove to facilitate 1,2-diacyl
      glycerol (DAG) binding or other agonist molecule for PKC activation. Post
      activation, a partial or complete blocking of hydrophilic groove makes the DAG
      binding site completely hydrophobic and facilitates easier penetration of the PKC
      into the membrane. Phorbol ester, a strong PKC agonist, uses this mechanism to
      induce tumor formation. A total of 300 heterocyclic compounds with 70% similarity
      to phorbol 12-myristate 13-acetate (PMA) were selected, and virtual docking was
      performed with PKC-alpha as target. An initial screening indicated that most of
      the molecules fit well into the C1 domain and had better binding energy than PMA.
      Further analysis in a PMA competition experiment identified five molecules, Zc
      67913417, Zc 68601770, Zc 25726447, Zc 35376386 and Zc 49785214 as potent PKC
      agonists. In addition, as these compounds showed better binding than PMA, more
      interaction with PKC residues (hydrogen bonding and hydrophobic), and the top
      five hit molecules was potent enough to abolish carcinogenic effects of PMA.
      Searching the top heterocyclic compounds into the drug database gave a number of
      approved drugs. Testing two candidate drugs, nandrolone decanoate and budesonide,
      reduced cellular viability of HT1080 in a dose-dependent manner with an IC50
      values of 96.8 nM and 200nM respectively. An in silico toxicity analysis
      indicated that top hit molecules are non-toxic, non-mutagenic in cellular and
      bacterial system, and have no tumorigenic potentials in a single cell or animal
      model. Hence, a virtual screening, agonist competition assay, and in silico
      toxicity assessment allowed us to identify five new PKC agonist molecules for
      future drug discovery against cancer. 

PMID- 24138400
TI  - Virtual reality training improves da Vinci performance: a prospective trial.
AB  - INTRODUCTION: The DV-TrainerTM (a virtual reality [VR] simulator) (Mimic
      Technologies, Inc., Seattle, WA) is one of several different robotic surgical
      training methods. We designed a prospective study to determine whether VR
      training could improve da Vinci((r)) Surgical System (Intuitive Surgical, Inc.,
      Sunnyvale, CA) performance. SUBJECTS AND METHODS: Surgeons (n=12) were enrolled
      using a randomized protocol. Groups 1 (VR training) and 2 (control) participated
      in VR and da Vinci exercises. Participants' time and moving distance were
      combined to determine a composite score: VR index=1000/(time*moving distance).
      The da Vinci exercises included needle control and suturing. Procedure time and
      error were measured. A composite index (DV index) was computed and used to
      measure da Vinci competency. After the initial trial with both the VR and da
      Vinci exercises, only Group 1 was trained with the VR simulator following our
      institutional curriculum for 3 weeks. All members of both groups then
      participated in the second trial of the VR and da Vinci exercises and were scored
      in the same way as in the initial trial. RESULTS: In the initial trial, there was
      no difference in the VR index (Group 1 versus Group 2, 8.9 +/- 3.3 versus 9.4 +/-
      3.7; P=.832) and the DV index (Group 1 versus Group 2, 3.85 +/- 0.73 versus 3.66
      +/- 0.65; P=.584) scores between the two groups. At the second time point, Group
      1 showed increased VR index scores in comparison with Group 2 (19.3 +/- 4.5
      versus 9.7 +/- 4.1, respectively; P=.001) and improved da Vinci performance
      skills as measured by the DV index (5.80 +/- 1.13 versus 4.05 +/- 1.03,
      respectively; P=.028) and by suturing time (7.1 +/- 1.54 minutes versus 10.55 +/-
      1.93 minutes, respectively; P=.018). CONCLUSIONS: We found that VR simulator
      training can improve da Vinci performance. VR practice can result in an early
      plateau in the learning curve for robotic practice under controlled
      circumstances.

PMID- 24138401
TI  - Tuning omniphobicity via morphological control of metal-organic framework
      functionalized surfaces.
AB  - Fabrication of microstructures for imparting omniphobicity to a surface generally
      requires the use of lithographic techniques and specialized equipment. We report
      instead a simple strategy for the synthesis of microstructured surfaces via metal
      organic framework (MOF) self-assembly. Our method allows us to localize epitaxial
      growth of MOF at the tips of needle crystals to create mushroom-shaped
      structures, thus conferring re-entrant textures to the MOF-functionalized
      surfaces. These structures synthesized via wet chemistry were found to have
      omniphobic properties due to the resulting re-entrant texture.

PMID- 24138402
TI  - Review of lipiodol treatment for infertility - an innovative treatment for
      endometriosis-related infertility?
AB  - A lipiodol hysterosalpingogram was the routine test for tubal patency as recently
      as the 1970s. Observational studies, then randomised controlled trials, provided
      evidence of a fertility enhancing effect of lipiodol. It has been found to
      improve fertility for women with normal tubal patency, particularly where the
      woman has a history of endometriosis. Previous successful treatment for
      infertility with lipiodol is a marker of further successful treatment for
      infertility in a repeat procedure. Whilst lipiodol is probably effective at
      flushing debris that could hinder fertility from fallopian tubes, it also exerts
      immunobiological effects in pelvic peritoneum and on the endometrium that could
      be responsible for fertility enhancement. Effects of lipiodol on the endometrium
      that might be important at the time of the implantation window are a reduced
      expression of osteopontin and an increased number of uterine natural killer cells
      postlipiodol. The effect of lipiodol uterine bathing for women with
      endometriosis, repeat in vitro fertilisation (IVF) implantation failure and other
      reproductive disorders merits further investigation. Lipiodol presents a new,
      simple, low invasive, inexpensive treatment option for endometriosis-related
      infertility and might have wider applications. 

PMID- 24138403
TI  - Esophagitis in children: an update on current pharmacotherapy.
AB  - INTRODUCTION: A common diagnostic entity in children is Esophagitis with multiple
      etiologies and complex immuno-pathogenic mechanisms. Our understanding of these
      mechanisms and of the pharmacotherapy of esophagitis is still evolving. AREAS
      COVERED: Areas of focus for this review were chosen based on recent clinical
      practice and research interest in esophagitis in infants and children. A
      literature search was conducted with the relevant keywords ('gastroesophageal
      reflux disease' in pediatric age group, 'eosinophilia', 'esophageal
      eosinophilia', 'esophagitis', 'eosinophilic esophagitis', 'proton pump
      inhibitors'). Use, safety and efficacy of proton pump inhibitors in young infants
      and older children, the concepts of esophageal eosinophilia and overlap of reflux
      and eosinophilic esophagitis are discussed here. EXPERT OPINION: Proton pump
      inhibitors are effective in healing reflux esophagitis in children of all ages
      but do not improve gastroesophageal reflux related symptoms in infants. An
      overlap in clinical and histological features of reflux and eosinophilic
      esophagitis exists, and proton pump inhibitors may exert their action in pathways
      other than just acid suppression. The role of weakly acidic/alkaline reflux in
      gastroesophageal reflux symptoms, development of newer reflux modifying
      medications and tools to assess efficacy of therapeutic intervention in
      eosinophilic esophagitis are promising areas for further research and developing
      knowledge.

PMID- 24138405
TI  - Modelling response selection in task switching: testing the contingent encoding
      assumption.
AB  - The contingent encoding assumption is the idea that response selection in task
      switching situations does not begin until the cue and the target have both been
      encoded. The authors tested the assumption by manipulating response congruency,
      stimulus order, and stimulus onset asynchrony (SOA) in two experiments. They
      found evidence of response selection prior to cue encoding for congruent targets
      with target-cue order at a long SOA, indicating that the contingent encoding
      assumption is invalid. The authors describe how contingent encoding can be
      removed from an existing task-switching model by introducing baseline evidence-
      task-neutral evidence that serves as a baseline for response selection prior to
      stimulus encoding. Simulations revealed that the modified model could reproduce
      the full pattern of response time data and generate responses prior to cue
      encoding. The authors conclude by discussing directions for further model
      development.

PMID- 24138406
TI  - Fluid shear stress pre-conditioning promotes endothelial morphogenesis of
      embryonic stem cells within embryoid bodies.
AB  - Pluripotent embryonic stem cells (ESCs) are capable of differentiating into all
      mesoderm-derived cell lineages, including endothelial, hematopoietic, and cardiac
      cell types. Common strategies to direct mesoderm differentiation of ESCs rely on
      exposing the cells to a series of biochemical and biophysical cues at different
      stages of differentiation to promote maturation toward specific cell phenotypes.
      Shear forces that mimic cardiovascular physiological forces can evoke a myriad of
      responses in somatic and stem cell populations, and have, thus, been studied as a
      means to direct stem cell differentiation. However, elucidating the effects of
      shear pre-conditioning on the subsequent vascular differentiation and
      morphogenesis of ESCs has yet to be examined. In this study, ESC monolayers were
      subjected to physiological shear (5 dyn/cm(2)) or static conditions for 2 days on
      collagen IV-coated substrates before initiating embryoid body (EB)
      differentiation. Immediately after the pre-conditioning period, shear pre
      conditioned and statically cultured ESCs exhibited similar morphologies and
      largely retained a pluripotent phenotype; however, ESCs exposed to fluid shear
      expressed increased levels of endothelial marker genes Flk-1 (~3-fold), VE
      cadherin (~3-fold), and PECAM (~2-fold), compared with statically cultured ESCs.
      After 7 days of EB culture, ~70% of EBs formed from shear pre-conditioned ESCs
      expressed significantly higher levels of endothelial marker genes compared with
      EBs formed from statically cultured ESCs. Interestingly, unlike EBs formed from
      statically cultured ESCs, EBs formed from fluid shear stress pre-conditioned ESCs
      exhibited a centrally localized region of VE-cadherin(+) cells that persisted for
      at least 10 days of differentiation. These results demonstrate that fluid shear
      stress pre-conditioning not only promotes ESC endothelial gene expression but
      also subsequently impacts the organization of endothelial cells within EBs.
      Together, these studies highlight a novel approach to promote in vitro
      morphogenesis of developmental vasculogenic models and potentially promote pre
      vascularization of tissue-engineered constructs derived from pluripotent stem
      cells. 

PMID- 24138408
TI  - The eye movement desensitization and reprocessing procedure prevents defensive
      processing in health persuasion.
AB  - In the present study, the method of eye movement desensitization and reprocessing
      (EMDR) is studied to understand and prevent defensive reactions with regard to a
      negatively framed message advocating fruit and vegetable consumption. EMDR has
      been shown to tax the working memory. Participants from a university sample (n =
      124) listened to the persuasive message in a randomized laboratory experiment. In
      the EMDR condition, they were also instructed to follow with their eyes a dot on
      the computer screen. The dot constantly moved from one side of the screen to the
      other in 2 seconds. In addition, a self-affirmation procedure was applied in half
      of the participants. EMDR led to a significant increase in persuasion, only in
      recipients in whom the persuasive message could be expected to activate defensive
      self-regulation (in participants with a moderate health value and in participants
      with low self-esteem). In those with a moderate health value, EMDR increased
      persuasion, but only when recipients were not affirmed. In addition, EMDR
      increased persuasion only in recipients with low self-esteem, not in those with
      high self-esteem. These results showed that EMDR influenced persuasion and in
      some way lowered defensive reactions. The similarities and differences in effects
      of EMDR and self-affirmation further increased our insight into the psychology of
      defensiveness. 

PMID- 24138407
TI  - De novo transcriptome profiling uncovers a drastic downregulation of
      photosynthesis upon nitrogen deprivation in the nonmodel green alga
      Botryosphaerella sudeticus.
AB  - BACKGROUND: Neutral lipid storage is enhanced by nitrogen deprivation (ND) in
      numbers of green microalgal species. However, little is known about the metabolic
      pathways whose transcription levels are most significantly altered following ND
      in green microalgae, especially the nonmodel species. RESULTS: To start gaining
      knowledge on this, we performed transcriptome profiling of the nonmodel green
      microalga Botryosphaerella sudeticus cells in response to ND. Transcriptome of B.
      sudeticus is de novo assembled based on millions of HiSEQ short sequence reads
      using CLC Genomics Workbench software. The resulting non-redundant ESTs are
      annotated based on the best hits generated from the BLASTX homology comparison
      against the "best" proteins in the model microalgae Chlamydomonas reinhardtii and
      Chlorella variabilis. By using a pathway-based approach according to KEGG
      databases, we show that ESTs encoding ribosomal proteins and photosynthetic
      functions are the most abundantly expressed ESTs in the rapidly growing B.
      sudeticus cells. We find that ESTs encoding photosynthetic function but not the
      ribosomal proteins are most drastically downregulated upon ND. Notably, ESTs
      encoding lipid metabolic pathways are not significantly upregulated. Further
      analyses indicate that chlorophyll content is markedly decreased by 3-fold and
      total lipid content is only slightly increased by 50%, consistent with the
      transcriptional profiling. On the other hand, carbon content and photosynthesis
      efficiency are only marginally decreased by 7% and 20%, respectively, indicating
      that photosynthesis is only slightly reduced upon drastic downregulation of
      photosynthetic ESTs and chlorophyll content upon ND. In addition, TAG content is
      found to be greatly increased by 50-fold, though total lipid content is only
      slightly increased by 1.5-fold. CONCLUSIONS: Taken together, our results suggest
      that light-harvesting proteins and chlorophylls are in excess in B. sudeticus.
      Degradation of excess photosynthesis proteins is most likely a mechanism for
      recycling of nitrogen-rich molecules to synthesize new proteins for preparation
      of gametogenesis and zygospore formation in adaptation and survival upon ND.
      Furthermore, our analyses indicate that TAG accumulation is largely attributed to
      the modification of other pre-existing lipid molecules, rather than de novo
      synthesis. We propose that this is likely an evolutionarily conserved mechanism
      in many green microalgae species.

PMID- 24138409
TI  - Infrared-actuated recovery of polyurethane filled by reduced graphene
      oxide/carbon nanotube hybrids with high energy density.
AB  - Optically actuated shape recovery materials receive much interest because of
      their great ability to control the creation of mechanical motion remotely and
      precisely. An infrared (IR) triggered actuator based on shape recovery was
      fabricated using polyurethane (TPU) incorporated by sulfonated reduced graphene
      oxide (SRGO)/sulfonated carbon nanotube (SCNT) hybrid nanofillers. Interconnected
      SRGO/SCNT hybrid nanofillers at a low weight loading of 1% dispersed in TPU
      showed good IR absorption and improved the crystallization of soft segments for a
      large shape deformation. The output force, energy density and recovery time of IR
      triggered actuators were dependent on weight ratios of SRGO to SCNT (SRGO:SCNT).
      TPU nanocomposites filled by a hybrid nanofiller with SRGO:SCNT of 3:1 showed the
      maximum IR-actuated stress recovery of lifting a 107.6 g weight up 4.7 cm in 18
      s. The stress recovery delivered a high energy density of 0.63 J/g and shape
      recovery force up to 1.2 MPa due to high thermal conductivity (1.473 W/mK) and
      Young's modulus of 23.4 MPa. Results indicate that a trade-off between the
      stiffness and efficient heat transfer controlled by synergistic effect between
      SRGO and SCNT is critical for high mechanical power output of IR-triggered
      actuators. IR-actuated shape recovery of SRGO/SCNT/TPU nanocomposites combining
      high energy density and output forces can be further developed for advanced
      optomechanical systems. 

PMID- 24138410
TI  - Technique for office-based, ultrasonography-guided percutaneous biopsy of renal
      cortical neoplasms using a novel transducer for facilitated ultrasound targeting.
AB  - OBJECTIVES: To help clarify which small renal cortical neoplasms (RCNs) require
      surgery by using office-based, ultrasonography-guided percutaneous renal biopsy.
      PATIENTS AND METHODS: Biopsies were performed using facilitated ultrasound
      targeting (FUT) technology, which incorporates a needle guide and onscreen beam
      steered technology to permit highly precise needle deployment. Patient and tumour
      characteristics, procedure time, complications and biopsy efficacy were
      documented. Wong-Baker pain levels were obtained before, during and 1 h after the
      procedure. RESULTS: Seven patients underwent biopsy, six for RCNs and one for
      medical renal disease. The mean (range) patient age was 68.5 (54-79) years, and
      the mean (range) tumour diameter was 2.55 (2.0-2.9) cm. Mean pain levels before,
      during and 1 h after the procedure were 0, 1.6 and 0.5, respectively. There were
      no intra- or post-procedural complications. Biopsy results were diagnostic in
      five of the six RCN cases and in the single case of medical renal disease.
      CONCLUSIONS: Our preliminary experience shows that office-based percutaneous
      renal biopsy using a novel transducer for FUT is safe and effective. An
      international multicentre study is planned to confirm these preliminary results.

PMID- 24138411
TI  - Comparison of physician referral and insurance claims data-based risk prediction
      as approaches to identify patients for care management in primary care: an
      observational study.
AB  - BACKGROUND: Primary care-based care management (CM) could reduce hospital
      admissions in high-risk patients. Identification of patients most likely to
      benefit is needed as resources for CM are limited. This study aimed to compare
      hospitalization and mortality rates of patients identified for CM either by
      treating primary care physicians (PCPs) or predictive modelling software for
      hospitalization risk (PM). METHODS: In 2009, a cohort of 6,026 beneficiaries of a
      German statutory health insurance served as a sample for patient identification
      for CM by PCPs or commercial PM (CSSG 0.8, Verisk Health). The resulting samples
      were compared regarding hospitalization and mortality rates in 2010 and in the
      two year period before patient selection. No CM-intervention was delivered until
      the end of 2010 and PCPs were blinded for the assessment of hospitalization
      rates. RESULTS: In 2010, hospitalization rates of PM-identified patients were 80%
      higher compared to PCP-identified patients. Mortality rates were also 8% higher
      in PM-identified patients if compared to PCP-identified patients (10% vs. 2%).
      The hospitalization rate of patients independently identified by both PM and PCPs
      was numerically between PM- and PCP-identified patients. Time trend between 2007
      and 2010 showed decreasing hospitalization rates in PM-identified patients (-15%
      per year) compared to increasing rates in PCP-identified patients (+34% per
      year). CONCLUSIONS: PM identified patients with higher hospitalization and
      mortality rates compared to PCP-referred patients. But the latter showed
      increasing hospitalization rates over time thereby suggesting that PCPs may be
      able to predict future deterioration in patients with relatively good current
      health status. These patients may most likely benefit from preventive services
      like CM.

PMID- 24138412
TI  - Ultrafast charge separation in organic photovoltaics enhanced by charge
      delocalization and vibronically hot exciton dissociation.
AB  - In organic photovoltaics, the mechanism by which free electrons and holes are
      generated, overcoming the Coulomb attraction, is a currently much debated topic.
      To elucidate this mechanism at a molecular level, we carried out a combined
      electronic structure and quantum dynamical analysis that captures the elementary
      events from the exciton dissociation to the free carrier generation at
      polymer/fullerene donor/acceptor heterojunctions. Our calculations show that
      experimentally observed efficient charge separations can be explained by a
      combination of two effects: First, the delocalization of charges which
      substantially reduces the Coulomb barrier, and second, the vibronically hot
      nature of the charge-transfer state which promotes charge dissociation beyond the
      barrier. These effects facilitate an ultrafast charge separation even at low-band
      offset heterojunctions. 

PMID- 24138413
TI  - Childhood lichen planus pemphigoides: report of two cases treated successfully
      with systemic glucocorticoids and dapsone.
AB  - We describe two boys, ages 8 and 7 years, who developed lichen planus
      pemphigoides. In one of the boys, a henna tattoo probably triggered the disease.
      Therapy with systemic glucocorticoids and dapsone was successful. 

PMID- 24138414
TI  - Morphological characteristics and developmental changes of the ovary in the tick
      Haemaphysalis longicornis Neumann.
AB  - Haemaphysalis longicornis (Ixodida: Ixodidae) is an important vector of
      transovarially transmitted parasites of the genus Babesia (Piroplasmida:
      Babesiidae). In the present study, we investigated the morphological
      characteristics and developmental changes of the ovary of H. longicornis. We show
      that the ovary of H. longicornis has a single tubular structure and is surrounded
      by a tunica propria. There is a longitudinal groove along one side of the ovary.
      During feeding and after engorgement, great changes can be observed in the ovary
      of H. longicornis and two rapid growth phases can be detected. The number of
      major protein bands of the ovary is significantly increased from day 3 of feeding
      and reaches a maximum on the day of engorgement. Therefore, the great diversity
      of proteins in the ovaries of H. longicornis can facilitate the identification of
      new targets for vaccine development.

PMID- 24138415
TI  - Histidine hydrogen bonding in MHC at pH 5 and pH 7 modeled by molecular docking
      and molecular dynamics simulations.
AB  - Hydrogen bonds play important roles in maintaining the structure of proteins and
      in the formation of most biomolecular protein-ligand complexes. All amino acids
      can act as hydrogen bond donors and acceptors. Among amino acids, Histidine is
      unique, as it can exist in neutral or positively charged forms within the
      physiological pH range of 5.0 to 7.0. Histidine can thus interact with other
      aromatic residues as well as forming hydrogen bonds with polar and charged
      residues. The ability of His to exchange a proton lies at the heart of many
      important functional biomolecular interactions, including immunological ones. By
      using molecular docking and molecular dynamics simulation, we examine the
      influence of His protonation/deprotonation on peptide binding affinity to MHC
      class II proteins from locus HLA-DP. Peptide-MHC interaction underlies the
      adaptive cellular immune response, upon which the next generation of commercially
      important vaccines will depend. Consistent with experiment, we find that peptides
      containing protonated His residues bind better to HLA-DP proteins than those with
      unprotonated His. Enhanced binding at pH 5.0 is due, in part, to additional
      hydrogen bonds formed between peptide His(+) and DP proteins. In acidic
      endosomes, protein His(79beta) is predominantly protonated. As a result, the
      peptide binding cleft narrows in the vicinity of His(79beta), which stabilizes
      the peptide - HLA-DP protein complex. 

PMID- 24138416
TI  - Computationally designed atovaquone prodrugs based on Bruice's enzyme model.
AB  - DFT molecular orbital calculations at B3LYP 6-31G (d,p) and B3LYP/311+G (d,p)
      levels and molecular mechanics (MM2) calculations of kinetic properties for
      Bruice's systems 1-5 indicate that the rate enhancement in the cyclization of di
      carboxylic semi-esters 1-5 is solely the result of strain effects and not
      proximity orientation 'reactive rotamer effect". Furthermore, it was found that
      the activation energy in systems 1-5 and atovaquone ProD1- ProD5 is largely
      dependent on the difference in the strain energies of the tetrahedral
      intermediates and reactants, and no correlation was found between the cyclization
      rate and distance between the nucleophile and the electrophile (rGM). Using the
      experimental t1/2 (the time needed for the conversion of 50% of the reactants to
      products) value for the cyclization reaction of di-carboxylic semi-ester 1 and
      the calculated log krel values for prodrugs ATQ ProD1- ProD5 the t1/2 values for
      the interconversion of ATQ ProD1- ProD5 to the parent drug were calculated.
      Thet1/2 values were: ATQ ProD3, 22.44 hours; ATQ ProD1, ATQ ProD2 and ATQ ProD4,
      few seconds and ATQ ProD5 few years. Therefore, the interconversion rate of
      atovaquone prodrugs to atovaquone can be programmed according to the nature of
      the prodrug linker. 

PMID- 24138417
TI  - QSAR analysis and molecular docking simulation of suggested peptidomimetic NS3
      protease inhibitors.
AB  - Based on the N-terminal hexapeptide product of hydrolysis (EDVVCC) at HCV NS5A/5B
      junction, three modified groups of compounds are built. The first group contains
      linear peptides while the second and third groups contain P1-P3 and P2-P4
      macrocyclic structures, respectively. Quantitative Structure Activity
      Relationship (QSAR) characterization and docking simulations are performed in
      order to investigate the potential of these compounds as HCV NS3/4A protease
      inhibitors. Based on the QSAR properties, the three most stable compounds due to
      their lowest total energy are P1-P3 and P2-P4 macrocycles of azahexapeptide
      sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azahexapeptide
      sequence (DDIVP norvaline). They also have high surface area, solvent accessible
      surface area, volume, molar refractivity and polarizabilty. They have moderately
      low dipole moment and good log P values, as well. The docking scores of the best
      two P2-P4 macrocycles are just acceptable. The two compounds 5A/5B hexapeptide
      sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azapentapeptide
      sequence (DIVP vinyl amino cyclopropane) yielded the best docking scores. 

PMID- 24138418
TI  - Graph theory concepts in the rationales of anti HIV-1 compounds.
AB  - Drug research is a multidisciplinary as well as resource intensive endeavor. In
      this the center of attention is biological response of an agent which gives the
      first insight of the activity (or receptor) space in the backdrop of chemical
      landscape. Here, molecular topology has significant role in explaining and
      exploring different phenomena associated with the chemical entities. Thus it
      provides direction to the design of therapeutic agents. In the backdrop the
      review highlighted the contribution of topological indices from different
      concepts in the HIV-1 drug research. In this article selected reports dealing
      with the topological descriptors in the QSARs of the anti-HIV-1 compounds acting
      as reverse transcriptase, protease and integrase inhibitors are appraised and
      elaborated. 

PMID- 24138419
TI  - A neural network-based QSAR approach for exploration of diverse multi-tyrosine
      kinase inhibitors and its comparison with a fragment- based approach.
AB  - Receptor and non-receptor tyrosine kinases have emerged as clinically useful drug
      target for treating certain types of cancer. It is well known that tyrosine
      kinase inhibitors with multi-kinases inhibitory potency are useful in anticancer
      therapy. In recent study, we have demonstrated application of a novel Group based
      QSAR (GQSAR) method to assist in lead optimization of multi-tyrosine kinase
      (PDGFR-beta, FGFR-1 and SRC) inhibitors. Although GQSAR method provides an
      alternative way to design new compounds, it could not be applied for virtual
      screening of large databases, because of its limitation to fragment each of the
      compound in the diverse database. So to circumvent this limitation of GQSAR
      method, herein we present the development of multi-kinase QSAR model using
      artificial neural networks. Various simple, easy and fast to calculate 2D/3D
      descriptors were used in the present analysis. The resulting neural network based
      QSAR (NN-QSAR) model was found to be statistically significant and provided
      insight into common structural requirements to inhibit different tyrosine
      kinases. The NN-QSAR model suggests five descriptors viz. number of rotatable
      bonds, number of hydrogen bond donors, number of building blocks, polar surface
      area and sum of nitrogen and oxygen atoms to be of major importance in explaining
      the activity variation in all the three kinases. In addition, this multi-target
      QSAR model could be useful to predict the activities of new compounds designed as
      tyrosine kinase inhibitors. 

PMID- 24138420
TI  - Adapting interrelated two-way clustering method for quantitative structure
      activity relationship (QSAR) modeling of mutagenicity/non- mutagenicity of a
      diverse set of chemicals.
AB  - Interrelated Two-way Clustering (ITC) is an unsupervised clustering method
      developed to divide samples into two groups in gene expression data obtained
      through microarrays, selecting important genes simultaneously in the process.
      This has been found to be a better approach than conventional clustering methods
      like K-means or selforganizing map for the scenarios when number of samples is
      much smaller than number of variables (n"p). In this paper we used the ITC
      approach for classification of a diverse set of 508 chemicals regarding
      mutagenicity. A large number of topological indices (TIs), 3-dimensional, and
      quantum chemical descriptors, as well as atom pairs (APs) has been used as
      explanatory variables. In this paper, ITC has been used only for predictor
      selection, after which ridge regression is employed to build the final predictive
      model. The proper leave-one-out (LOO) method of cross-validation in this scenario
      is to take as holdout each of the 508 compounds before predictor thinning and
      compare the predicted values with the experimental data. ITC based results
      obtained here are comparable to those developed earlier. 

PMID- 24138421
TI  - Lemont B. Kier: a bibliometric exploration of his scientific production and its
      use.
AB  - We thought an appropriate way to celebrate the seminal contribution of Kier is to
      explore his influence on science, looking for the impact of his research through
      the citation of his scientific production. From a bibliometric approach the
      impact of Kier's work is addressed as an individual within a community. Reviewing
      data from his curriculum vitae, as well as from the ISI Web of Knowledge (ISI),
      his role within the scientific community is established and the way his
      scientific results circulate is studied. His curriculum vitae is explored
      emphasising the approaches he used in his research activities and the social ties
      with other actors of the community. The circulation of Kier's publications in the
      ISI is studied as a means for spreading and installing his discourse within the
      community. The citation patterns found not only show the usage of Kier's
      scientific results, but also open the possibility to identify some
      characteristics of this discursive community, such as a common vocabulary and
      common research goals. The results show an interdisciplinary research work that
      consolidates a scientific community on the topic of drug discovery. 

PMID- 24138422
TI  - Mathematical descriptors for the prediction of property, bioactivity, and
      toxicity of chemicals from their structure: a chemical-cum-biochemical approach.
AB  - This review article covers major aspects of mathematical chemistry, QSAR,
      chemoinformatics, bioinformatics, and molecular modeling research carried out by
      Subhash C. Basak and coworkers during 1968 to the present time in three distinct
      phases: 1) Department of Biochemistry, University of Calcutta and Charuchandra
      College, India (1968-1981); 2) Department of Chemistry & Biochemistry, University
      of Minnesota, Duluth, USA (1982-1987), and 3) Natural Resources Research
      Institute, University of Minnesota, Duluth, UMD-NRRI (1988-date). Topics
      discussed include development of novel mathematical descriptors of molecules and
      biomolecules; QSAR, HiQSAR, DiffQSAR and I-QSAR studies using chemodescriptors
      and biodescriptors; formulation of arbitrary quantitative molecular similarity
      analysis (QMSA) and tailored QMSA methods and their applications. The role of
      proper statistical methods in QSAR formulation and validation as well as the
      critical role of such methods in the molecular descriptor landscape of the twenty
      first century are also addressed. 

PMID- 24138423
TI  - Topological and electrotopological descriptors of molecules: fundamental
      principles and applications to computer-aided molecular design - III.

PMID- 24138424
TI  - The construction of cloned Sika deer embryos (Cervus nippon hortulorum) by
      demecolcine auxiliary enucleation.
AB  - The objective of our study was to establish the feasibility of experimental
      protocols for cloning sika deer. We performed auxiliary enucleation to improve
      the efficiency of nuclear transfer operation by optimizing the demecolcine
      concentration to induce cytoplasmic protrusions in the sika deer oocytes. In the
      present study,we had studied the impact of different demecolcine concentrations
      on cytoplasmic protrusions and enucleation rates. We determined that 95.9% of the
      sika deer oocytes formed cytoplasmic protrusions when treated for 1 h with 0.8
      MUg/ml demecolcine. The lowest observed rate of protrusion was 19.3% after
      overnight treatment with demecolcine. When the oocytes aged or had a poor cumulus
      expansion, they exhibited a significant decrease in the ability to form
      cytoplasmic protrusions. The rates of enucleation (94.9% vs 85.8%, p < 0.05),
      cell fusion (84.6% vs 70.1%, p < 0.05) and blastocyst formation (15.4% vs 10.9%,
      p < 0.05) using demecolcine auxiliary enucleation were significantly higher than
      those after blind enucleation. These results demonstrated that sika deer oocytes
      could be enucleated quickly and effectively using demecolcine auxiliary
      enucleation, which could enhance the enucleation rate, cell fusion rate and
      blastocyst rate of cloned embryos in vitro. 

PMID- 24138425
TI  - Incorporation of antimicrobial macromolecules in acrylic denture base resins: a
      research composition and update.
AB  - Contemporary research in acrylic denture base materials focuses on the
      development of a novel poly(methyl methacrylate) (PMMA) resin with antimicrobial
      properties. Although PMMA resin has fulfilled all the requirements of an ideal
      denture base material, its susceptibility to microbial colonization in the oral
      environment is a formidable concern to clinicians. Many mechanisms including the
      absence of ionic charge in the methyl methacrylate resins, hydrophobic
      interactions, electrostatic interactions, and mechanical attachment have been
      found to contribute to the formation of biofilm. The present article outlines the
      basic categories of potential antimicrobial polymer (polymeric biocides)
      formulations (modified PMMA resins) and considers their applicability, biological
      status, and usage potential over the coming years. 

PMID- 24138426
TI  - Role of the renin-angiotensin system on abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex degenerative disease,
      which leads to morbidity and mortality in a large portion of the elderly
      population. Current treatment options for AAA are quite limited as there is no
      proven indication for pharmacological therapy and surgery is recommended for AAA
      larger than 5.5 cm in luminal diameter. Thus, there is a great need to elucidate
      the underlying pathophysiological cellular and molecular mechanisms to develop
      effective therapies. In this narrative review, we will discuss recent findings
      concerning some potential molecular and clinical aspects of the renin-angiotensin
      system (RAS) in AAA pathophysiology. MATERIALS AND METHODS: This narrative review
      is based on the material found on MEDLINE and PubMed up to April 2013. We looked
      for the terms 'angiotensin, AT1 receptor, ACE inhibitors' in combination with
      'abdominal aortic aneurysm, pathophysiology, pathways'. RESULTS: Several basic
      research and clinical studies have recently investigated the role of the RAS in
      AAA. In particular, the subcutaneous infusion of Angiotensin II has been shown to
      induce AAA in Apo56 knockout mice. On the other hand, the pharmacological
      treatments targeting this system have been shown as beneficial in AAA patients.
      CONCLUSIONS: Emerging evidence suggests that RAS may act as a molecular and
      therapeutic target for treating AAA. However, several issues on the role of RAS
      and the protective activities of angiotensin-converting enzyme (ACE) inhibitors
      and Angiotensin 1 receptors blockers against AAA require further clarifications.

PMID- 24138427
TI  - Changes in melatonin levels in transgenic 'Micro-Tom' tomato overexpressing ovine
      AANAT and ovine HIOMT genes.
AB  - In animals, the melatonin biosynthesis pathway has been well defined after the
      isolation and identification of the four key genes that are involved in the
      conversion of tryptophan to melatonin. In plants, there are special alternative
      catalyzing steps, and plant genes share very low homology with the animal genes.
      It was of interest to examine the phenotype of transgenic Micro-Tom tomato plants
      overexpressing the homologous sheep oAANAT and oHIOMT genes responsible for the
      last two steps of melatonin synthesis. The oAANAT transgenic plants have higher
      melatonin levels and lower indoleacetic acid (IAA) contents than control due to
      the competition for tryptophan, the same precursor for both melatonin and IAA.
      Therefore, the oAANAT lines lose the 'apical dominance' inferring that melatonin
      likely lacks auxin activity. The significantly higher melatonin content in oHIOMT
      lines than oAANAT lines provides new proof for the important role of ASMT in
      plant melatonin synthesis. In addition, the enhanced drought tolerance of oHIOMT
      lines will also be an important contribution for plant engineering. 

PMID- 24138428
TI  - Review of rank-based procedures for multicenter clinical trials.
AB  - This article reviews nonparametric alternatives to the mixed model normal theory
      analysis for the analyses of multicenter clinical trials. Under a mixed model,
      the traditional analysis is based on maximum likelihood theory under normal
      errors. This analysis, though, is not robust to outliers. Robust, rank-based,
      Wilcoxon-type procedures are reviewed for a multicenter clinical trial for the
      mixed model but without the assumption of normality. These procedures retain the
      high efficiency of Wilcoxon methods for simple location problems and are based on
      a fitting criterion which is robust to outliers in response space. A simple
      weighting scheme can be employed so that the procedures are robust to outliers in
      factor (design) space as well as response space. These rank-based analyses offer
      a complete analysis, including estimation of fixed effects and their standard
      errors, and tests of linear hypotheses. Both rank-based estimates of contrasts
      and individual treatment effects are reviewed. We illustrate the analyses using
      real data from a clinical trial. 

PMID- 24138429
TI  - Model-based estimates of long-term persistence of induced HPV antibodies: a
      flexible subject-specific approach.
AB  - In infectious diseases, it is important to predict the long-term persistence of
      vaccine-induced antibodies and to estimate the time points where the individual
      titers are below the threshold value for protection. This article focuses on HPV
      16/18, and uses a so-called fractional-polynomial model to this effect, derived
      in a data-driven fashion. Initially, model selection was done from among the
      second- and first-order fractional polynomials on the one hand and from the
      linear mixed model on the other. According to a functional selection procedure,
      the first-order fractional polynomial was selected. Apart from the fractional
      polynomial model, we also fitted a power-law model, which is a special case of
      the fractional polynomial model. Both models were compared using Akaike's
      information criterion. Over the observation period, the fractional polynomials
      fitted the data better than the power-law model; this, of course, does not imply
      that it fits best over the long run, and hence, caution ought to be used when
      prediction is of interest. Therefore, we point out that the persistence of the
      anti-HPV responses induced by these vaccines can only be ascertained empirically
      by long-term follow-up analysis. 

PMID- 24138430
TI  - Dose-time-response modeling using negative binomial distribution.
AB  - People exposed to certain diseases are required to be treated with a safe and
      effective dose level of a drug. In epidemiological studies to find out an
      effective dose level, different dose levels are applied to the exposed and a
      certain number of cures is observed. Negative binomial distribution is considered
      to fit overdispersed Poisson count data. This study investigates the time effect
      on the response at different time points as well as at different dose levels. The
      point estimation and confidence bands for ED(100p)(t) and LT(100p)(d) are
      formulated in closed form for the proposed dose-time-response model with the
      negative binomial distribution. Numerical illustrations are carried out in order
      to check the performance level of the proposed model.

PMID- 24138431
TI  - Homogeneity test of difference between two correlated proportions in stratified
      matched-pair studies.
AB  - Stratified matched-pair studies are often designed for adjusting stratification
      factors in modern medical researches. This article investigates a homogeneity
      test of differences between two correlated proportions in stratified matched-pair
      studies. We propose three test procedures, including an asymptotic test,
      bootstrap test, and multiple comparison procedures, and determine sample size
      requirements for such tests in a stratified matched-pair study. Simulation
      studies are conducted to evaluate the performance of the three test procedures
      and the accuracy of our derived sample size formulas. Empirical results show that
      (1) the likelihood ratio statistic is robust, while the score statistic and the
      modified score statistic are conservative in some cases of our considered
      settings; (2) the likelihood ratio statistic and the score statistic with the
      bootstrap method and the MaxT procedure behave satisfactorily in the sense that
      their type I error rates are close to the pre-given significance level; and (3)
      the derived sample size formulas are rather accurate. A real example from a
      clinical laboratory study is used to illustrate the proposed methodologies. 

PMID- 24138432
TI  - Evaluation of overall treatment effect in MMRM.
AB  - In longitudinal clinical trials for drug development, the study objective is
      often to evaluate overall treatment effect across all visits. Despite careful
      planning and study conduct, the occurrence of incomplete data cannot be
      completely eliminated. As a direct likelihood method, the mixed-effects model for
      repeated measures (MMRM) has become one of the preferred approaches for handling
      missing data in such designs. MMRM is a full multivariate model in nature, which
      avoids potential bias as a predetermined model, and operates in a more general
      missing-at-random (MAR) framework. However, if treatment effect is constant over
      time, overparameterization of treatment by time interaction in MMRM could result
      in loss of power. In this article, we utilize MMRM estimates and propose an
      optimal weighting method for combining visit-specific estimates to maximize the
      power under MAR mechanism. For a special case where the underlying covariance is
      compound symmetry, we show that the optimal weighting method is asymptotically
      equal to MMRM. In other words, MMRM has optimal power under this special case.
      When the underlying covariance is of an unstructured pattern, the optimal
      weighting method has increased power under MAR and missing-not-at-random (MNAR)
      mechanisms, and can lead to bias reduction under MNAR. This is especially true
      when the variance is greater at later time point, which could lead to a smaller
      weight. We present practical examples using the optimal weighting method to
      analyze two cystic fibrosis clinical trial data sets. 

PMID- 24138433
TI  - Notes on testing noninferiority in ordinal data under the parallel groups design.
AB  - When testing the noninferiority of an experimental treatment to a standard (or
      control) treatment in a randomized clinical trial (RCT), we may come across the
      outcomes of patient response on an ordinal scale. We focus our discussion on
      testing noninferiority in ordinal data for an RCT under the parallel groups
      design. We develop simple test procedures based on the generalized odds ratio
      (GOR). We note that these test procedures not only can account for the
      information on the order of ordinal responses without assuming any specific
      parametric structural model, but also can be independent of any arbitrarily
      subjective scoring system. We further develop sample size determination based on
      the test procedure using the GOR. We apply Monte Carlo simulation to evaluate the
      performance of these test procedures and the accuracy of sample size calculation
      formula proposed here in a variety of situations. Finally, we employ the data
      taken from a trial comparing once-daily gatifloxican with three-times-daily co
      amoxiclav in the treatment of community-acquired pneumonia to illustrate the use
      of these test procedures and sample size calculation formula. 

PMID- 24138434
TI  - Sample size determination in two-sided distribution-free treatment versus control
      multiple comparisons.
AB  - The problem of power and sample size determination for distribution-free multiple
      comparison tests of K treatments versus a control group is addressed. We define
      the power as the probability of correctly rejecting one specified or all K
      hypotheses, corresponding to the per-pair and all-pairs power, respectively. The
      power formulas are derived for both joint ranking and pairwise ranking mechanism
      for general multiple comparison problems, followed by explicit form of these
      formulas when the single-step, step-down, or step-up adjustments are applied. The
      proposed power and sample size calculation methods apply to scenarios both when
      the underlying distributions are known and when they are unknown but a pilot
      study is available. Numerical methods via quasi-Monte Carlo integration and Monte
      Carlo integration are assessed. Our simulation studies show the accuracy of the
      power and sample size calculation formulas. We recommend the Monte Carlo
      integration as the calculation algorithm. An example from a mouse peritoneal
      cavity study is used to demonstrate the application of the methods. 

PMID- 24138435
TI  - A Bayesian design space for analytical methods based on multivariate models and
      predictions.
AB  - The International Conference for Harmonization (ICH) has released regulatory
      guidelines for pharmaceutical development. In the document ICH Q8, the design
      space of a process is presented as the set of factor settings providing
      satisfactory results. However, ICH Q8 does not propose any practical methodology
      to define, derive, and compute design space. In parallel, in the last decades, it
      has been observed that the diversity and the quality of analytical methods have
      evolved exponentially, allowing substantial gains in selectivity and sensitivity.
      However, there is still a lack of a rationale toward the development of robust
      separation methods in a systematic way. Applying ICH Q8 to analytical methods
      provides a methodology for predicting a region of the space of factors in which
      results will be reliable. Combining design of experiments and Bayesian standard
      multivariate regression, an identified form of the predictive distribution of a
      new response vector has been identified and used, under noninformative as well as
      informative prior distributions of the parameters. From the responses and their
      predictive distribution, various critical quality attributes can be easily
      derived. This Bayesian framework was then extended to the multicriteria setting
      to estimate the predictive probability that several critical quality attributes
      will be jointly achieved in the future use of an analytical method. An example
      based on a high-performance liquid chromatography (HPLC) method is given. For
      this example, a constrained sampling scheme was applied to ensure the modeled
      responses have desirable properties.

PMID- 24138436
TI  - Analysis of longitudinal trials with protocol deviation: a framework for
      relevant, accessible assumptions, and inference via multiple imputation.
AB  - Protocol deviations, for example, due to early withdrawal and noncompliance, are
      unavoidable in clinical trials. Such deviations often result in missing data.
      Additional assumptions are then needed for the analysis, and these cannot be
      definitively verified from the data at hand. Thus, as recognized by recent
      regulatory guidelines and reports, clarity about these assumptions and their
      implications is vital for both the primary analysis and framing relevant
      sensitivity analysis. This article focuses on clinical trials with longitudinal
      quantitative outcome data. For the target population, we define two estimands,
      the de jure estimand, "does the treatment work under the best case scenario," and
      the de facto estimand, "what would be the effect seen in practice." We then
      carefully define the concept of a deviation from the protocol relevant to the
      estimand, or for short a deviation. Each patient's postrandomization data can
      then be divided into predeviation data and postdeviation data. We set out an
      accessible framework for contextually appropriate assumptions relevant to de
      facto and de jure estimands, that is, assumptions about the joint distribution of
      pre- and postdeviation data relevant to the clinical question at hand. We then
      show how, under these assumptions, multiple imputation provides a practical
      approach to estimation and inference. We illustrate with data from a longitudinal
      clinical trial in patients with chronic asthma. 

PMID- 24138437
TI  - A profile analysis approach using MMRM in acute schizophrenia: a comparison to
      some traditional approaches.
AB  - The analysis of schizophrenia studies is plagued by inefficiency and bias due to
      much missing data. Mixed-effect models for repeated measures designs help address
      these problems, but to gain even more efficiency it is desirable to judiciously
      use additional longitudinal data in such designs by comparing treatment groups
      over multiple time points. Simulations were conducted to compare a profile
      analysis approach to other commonly used analysis methods in the presence of data
      missing at random. One gains efficiency by using a composite contrast over
      multiple time points when the treatment effect over the time points is not
      substantially different. 

PMID- 24138438
TI  - Covariate imbalance and adjustment for logistic regression analysis of clinical
      trial data.
AB  - In logistic regression analysis for binary clinical trial data, adjusted
      treatment effect estimates are often not equivalent to unadjusted estimates in
      the presence of influential covariates. This article uses simulation to quantify
      the benefit of covariate adjustment in logistic regression. However,
      International Conference on Harmonization guidelines suggest that covariate
      adjustment be prespecified. Unplanned adjusted analyses should be considered
      secondary. Results suggest that if adjustment is not possible or unplanned in a
      logistic setting, balance in continuous covariates can alleviate some (but never
      all) of the shortcomings of unadjusted analyses. The case of log binomial
      regression is also explored. 

PMID- 24138439
TI  - Selection of hypothesis weights and ordering when testing multiple hypotheses in
      clinical trials.
AB  - This article discusses the problem of selecting free parameters of multiple
      testing procedures in confirmatory Phase III clinical trials with multiple
      objectives, including hypothesis weights and hypothesis ordering. We identify
      classes of multiple testing procedures that provide different interpretations of
      these parameters. This includes basic single-step procedures (Bonferroni
      procedure) that employ fixed hypothesis weights, as well as more powerful
      stepwise procedures (Holm, fallback, and chain procedures) that reweight the
      hypotheses during the testing process. We examine the behavior of different
      classes of multiple testing procedures in problems with unequally weighted
      hypotheses and a priori ordered hypotheses and provide practical guidelines for
      the choice of hypothesis weights and hypothesis ordering. The concepts discussed
      in the article are illustrated using case studies based on clinical trials with
      multiple endpoints, multiple dose-placebo comparisons, and multiple patient
      populations. 

PMID- 24138440
TI  - A multilevel model for hierarchical, repeated, and overdispersed time-to-event
      outcomes and its estimation strategies.
AB  - The aim of this article is to propose a multilevel combined model for repeated,
      hierarchical, and overdispersed time-to-event outcomes, extending the so-called
      combined model proposed by Molenberghs et al. (2010), and using three different
      estimation strategies: full likelihood, pseudo-likelihood, and Bayesian
      estimation. For the first two estimation methods, we implemented the alternating
      imputation posterior (AIP) algorithm (Clayton and Rasbash, 1999). It is shown
      that the multilevel combined model can be fitted nicely using all three
      estimation methods. In addition, the multilevel combined model has the advantage
      that it not only can capture the hierarchical structure of the data but also can
      accommodate overdispersion within the data set. From our simulation results, it
      follows that the multilevel combined model performs well in terms of point
      estimation and its precision, fitted with the three different estimation methods.
      We also observed that pairwise likelihood estimation, a particular form of pseudo
      likelihood, is more time-intensive than full likelihood and Bayesian estimation.
      However, pseudo-likelihood estimation is less sensitive to starting values.

PMID- 24138441
TI  - Missing radiographic data handling in randomized clinical trials in rheumatoid
      arthritis.
AB  - In recent years, there has been increasing interest in compounds that have
      potential to slow down the structural joint damage in rheumatoid arthritis (RA)
      patients. Radiographs are instrumental in assessing structure damage in RA.
      Radiographic analyses results have become essential in establishing a "delay in
      structural progression" claim in newly developed agents for the treatment of RA.
      It is well known that the radiographic progression data generally follow a
      nonnormal distribution that is loaded with excessive zeros. A special concern
      about the radiographic data analyses is the handling of the seemingly high rate
      of missing values due to dropout or unreadable images. There are no uniform ways
      to handle missing radiographic data, and such data usually show considerable
      sensitivity to the imputation method chosen under the complexity of the nonnormal
      data and the unique missing mechanism. In this research, we proposed both an
      innovative multiple-imputation algorithm and a novel method called the mean rank
      imputation method under the nonparametric framework for sensitivity analyses. A
      simulation study was designed using rank analysis of covariance (ANCOVA) to
      extensively assess and compare the finite performance of these two new methods
      along with four other missing data handling methods previously used in the RA
      trials, namely, linear extrapolation, last observation carried-forward (LOCF),
      median quartile bin imputation, and median imputation under various settings. Our
      simulation results suggest that the multiple-imputation algorithm, providing an
      mITT analysis population, yields an inflated type I error and artificially good
      power. The proposed mean rank imputation method, following a true ITT principle,
      both is powerful and maintains type I error at the nominal level. 

PMID- 24138444
TI  - Long-term outcomes after progestogen treatment for early endometrial cancer.
AB  - BACKGROUND: For select women with early endometrial cancer, particularly
      nulliparous women, nonsurgical options may be considered. There is increasing
      experience using progestogens, but little is known about the long-term outcomes
      and safety of such treatment. AIMS: To present the cancer and pregnancy outcomes
      of women with greater than five years follow-up after progestogen treatment for
      early endometrial cancer. METHODS: Ten women who underwent greater than six
      months of continuous progestogen therapy for early endometrial cancer were
      included in the study. All were managed by a gynaecological oncologist at a major
      tertiary centre in Melbourne, Australia. The histology of each subsequent curette
      was recorded, as was the timing and histology of hysterectomy (if relevant), and
      the results of any subsequent pregnancies. RESULTS: All ten women showed
      histological regression of cancer with no cases of recurrence on follow-up
      curette. Four of ten women have undergone hysterectomy with one case of occult
      disease persistence in a woman noncompliant with therapy. The mean follow-up time
      was 89 months (range 62-142 months), there were no deaths and no woman was lost
      to follow-up. All four women attempting pregnancy were successful. There were
      eight pregnancies and five live births. CONCLUSIONS: This form of treatment
      appears to be successful and safe in the long term with good pregnancy outcomes.
      However, it is not standard and should be supervised in a specialised
      gynaecological oncology unit.

PMID- 24138445
TI  - A Narrative Inquiry: How do nurses respond to patients' use of humour?
AB  - Abstract In today's healthcare system where technical instruments and test
      results are used to implement care it is easy to lose the human aspect of
      nursing. Personal interaction can get lost and nurses sometimes miss humorous
      attempts made by patients. Humour is a very personal concept, what one person
      thinks is funny does not necessarily make another person smile, or might even be
      hurtful. Humour is an important communication tool for patients as it humanises
      the nurses, creates a bond and opens communication lines. Humour has the
      potential to change the hospital experience for patients. The aim of this paper
      is to highlight the importance of humour in the therapeutic relationship between
      patient-nurse. Semi structured interviews were held with four registered nurses
      and narrative inquiry was used to analyse and present the findings because of its
      ability to capture human interaction and experience.

PMID- 24138446
TI  - Clinical practice-changing trials: the HERA study paradigm.
AB  - Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the
      extracellular domain of this oncoprotein, represents the archetype of HER2
      blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast
      cancer (BC) led to its clinical development in the adjuvant setting. The
      HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which
      proved that this compound can change the natural course of early stage HER2
      positive BC. The HERA study led to the registration of trastuzumab for the
      adjuvant treatment of early HER2-positive BC. This trial randomized more than
      5000 patients between 1 and 2 years of trastuzumab and observation after the
      completion of locoregional therapy and (neo)-adjuvant chemotherapy. Additionally,
      an abundance of subsequent substudies were conducted, addressing important
      clinical issues for this patient population. The present review article presents
      a comprehensive overview of the HERA study and its major contributions to the
      adjuvant treatment of HER2-positive BC patients. Emphasis is given on the lessons
      learned from this international collaborative experience and how this can be used
      as a stepping stone for further improvements in the field. 

PMID- 24138447
TI  - Justice for the average Joe: the role of envy and the mentalizing network in the
      deservingness of others' misfortunes.
AB  - The misfortunes of enviable individuals are met by observers with pleasure
      whereas those of "average", non-enviable individuals elicit pain. These responses
      are mirrored in deservingness judgments, as enviable individuals' misfortunes are
      perceived as deserved and those of non-enviable individuals perceived as
      undeserved. However, the neural underpinnings of these deservingness disparities
      remain unknown. To explore this phenomenon, we utilized fMRI to test the
      hypotheses that (A) non-enviable targets' misfortunes would be associated with
      activation of brain regions that mediate empathic responding (pain matrix,
      mentalizing network) and not for enviable targets and (B) that activation of
      those regions would predict decreases in deservingness judgments. Supporting our
      first hypothesis, the misfortunes of non-enviable targets (as opposed to good
      fortunes) were associated with activation of the mentalizing network: medial
      prefrontal cortex, posterior cingulate cortex, temporal-parietal junction, and
      anterior temporal lobes. Supporting our second hypothesis, dorsomedial prefrontal
      cortex activation from this contrast was negatively correlated with subsequent
      reports of how much the non-enviable target deserved his/her misfortune. These
      findings suggest that non-enviable individuals' misfortunes are perceived as
      unjust due, in part, to the recruitment of the mentalizing network. 

PMID- 24138448
TI  - Using Del-1 to tip the angiogenic balance in endothelial cells in modular
      constructs.
AB  - Modular tissue engineering is a method of building vascularized tissue-engineered
      constructs. Submillimeter-sized collagen pieces (modules) coated with a layer of
      endothelial cells (EC; vascular component), and with embedded functional cells,
      are self-assembled into a larger, three-dimensional tissue. In this study, we
      examined the use of developmental endothelial locus-1 (Del-1), an extracellular
      matrix protein with proangiogenic properties, as a means of tipping the
      angiogenic balance in human umbilical vein endothelial cells incorporated in
      modular tissue-engineered constructs. The motivation was to enhance the
      vascularization of these constructs upon transplantation in vivo, in this case,
      without the use of exogenous mesenchymal stromal cells. EC were transduced using
      a lentiviral construct to overexpress Del-1. The Del-1 EC formed more sprouts in
      a fibrin gel sprouting assay in vitro compared with eGFP (control) transduced EC,
      as expected. Del-1 EC had a distinct profile of gene expression (upregulation of
      matrix metalloproteinase-9 [MMP-9], urokinase-type plasminogen activator
      [uPA/PLAU], vascular endothelial growth factor [VEGF-A], and intercellular
      adhesion molecule-1 [ICAM-1]; downregulation of angiopoietin-2 [Ang2]), also
      supporting the notion of "tipping the angiogenic balance". On the other hand,
      contrary to our expectations, when Del-1 EC-coated modules were implanted
      subcutaneously in a severe combined immunodeficient/beige animal model, the
      proangiogenic effect of Del-1 was less remarkable. There was only a small
      increase in the number of blood vessels formed in Del-1 implants compared with
      the eGFP implants, and only few blood vessels formed at the implant site in both
      cases. This was presumed due to limited EC survival after transplantation. We
      speculate that if we could improve EC survival in our study (for example, by
      adding other prosurvival factors or supporting cells), we would see a greater Del
      1-induced angiogenic benefit in vivo as a consequence of increased Del-1
      secretion by a higher number of surviving cells. 

PMID- 24138449
TI  - Global regulatory architecture of human, mouse and rat tissue transcriptomes.
AB  - BACKGROUND: Predicting molecular responses in human by extrapolating results from
      model organisms requires a precise understanding of the architecture and
      regulation of biological mechanisms across species. RESULTS: Here, we present a
      large-scale comparative analysis of organ and tissue transcriptomes involving the
      three mammalian species human, mouse and rat. To this end, we created a unique,
      highly standardized compendium of tissue expression. Representative tissue
      specific datasets were aggregated from more than 33,900 Affymetrix expression
      microarrays. For each organism, we created two expression datasets covering over
      55 distinct tissue types with curated data from two independent microarray
      platforms. Principal component analysis (PCA) revealed that the tissue-specific
      architecture of transcriptomes is highly conserved between human, mouse and rat.
      Moreover, tissues with related biological function clustered tightly together,
      even if the underlying data originated from different labs and experimental
      settings. Overall, the expression variance caused by tissue type was
      approximately 10 times higher than the variance caused by perturbations or
      diseases, except for a subset of cancers and chemicals. Pairs of gene orthologs
      exhibited higher expression correlation between mouse and rat than with human.
      Finally, we show evidence that tissue expression profiles, if combined with
      sequence similarity, can improve the correct assignment of functionally related
      homologs across species. CONCLUSION: The results demonstrate that tissue-specific
      regulation is the main determinant of transcriptome composition and is highly
      conserved across mammalian species.

PMID- 24138450
TI  - Prototropical and photophysical properties of ellipticine inside the nanocavities
      of molecular containers.
AB  - Host-guest interactions between an anticancer drug, ellipticine (EPT), and
      molecular containers (cucurbitruils (CBn) and cyclodextrins (CD)) are
      investigated with the help of steady state and time-resolved fluorescence
      measurements. Our experimental results confirm the formation of 1:1 inclusion
      complexes with CB7 and CB8. The protonated form of EPT predominantly prevails in
      the inclusion complexes due to the stabilization achieved through ion-dipole
      interaction between host and positively charged drug. Drug does not form an
      inclusion complex with CB6, which is smaller in cavity size compared to either
      CB7 or CB8. In the case of cyclodextrins, alpha-CD does not form an inclusion
      complex, whereas beta-CD forms a 1:1 inclusion complex with the protonated form
      of the drug, and the binding affinity of EPT with beta-CD is less compared to
      CB7/CB8. Interestingly, in the case of gamma-CD, drug exists in different forms
      depending on the concentration of the host. At lower concentration of gamma-CD,
      1:1 inclusion complex formation takes place and EPT exists in protonated form due
      to accessibility of water by the drug in the inclusion complex, whereas, at
      higher concentration, a 2:1 inclusion complex (gamma-CD:EPT) is observed, in
      which EPT is completely buried inside the hydrophobic cavity of the capsule
      formed by two gamma-CD molecules, and we believe the hydrophobic environment
      inside the capsule stabilizes the neutral form of the drug in the 2:1 inclusion
      complex. Deep insight into the molecular picture of these host-guest interactions
      has been provided by the docking studies followed by quantum chemical
      calculations. 

PMID- 24138451
TI  - Industrial steam systems and the energy-water nexus.
AB  - This paper presents estimates for water consumption and steam generation within
      U.S. manufacturing industries. These estimates were developed through the
      integration of detailed, industry-level fuel use and operation data with an
      engineering-based steam system model. The results indicate that industrial steam
      systems consume approximately 3780 TBTU/yr (3.98 * 10(9) GJ/yr) to generate an
      estimated 2.9 trillion lb/yr (1.3 trillion kg/yr) of steam. Since a good portion
      of this steam is injected directly into plant processes, vented, leaked, or
      removed via blowdown, roughly 354 MGD of freshwater must be introduced to these
      systems as makeup. This freshwater consumption rate is approximately 11% of that
      for the entire U.S. manufacturing sector, or the total residential consumption
      rate of Los Angeles, the second largest city in the U.S. The majority of this
      consumption (>94%) can be attributed to the food, paper, petroleum refining, and
      chemicals industries. The results of the analyses presented herein provide
      previously unavailable detail on water consumption in U.S. industrial steam
      systems and highlight opportunities for combined energy and water savings. 

PMID- 24138453
TI  - Leptin - a link between obesity and osteoarthritis. applications for prevention
      and treatment.
AB  - Osteoarthritis (OA) is the most common cause of musculoskeletal disability and
      pain in the world. The current drug treatment for OA is symptom relieving, and
      there is an urgent need for treatments that could retard, prevent or repair
      cartilage destruction in OA. Obesity is a major risk factor for OA.
      Traditionally, it has been thought to contribute to the development of OA by
      increasing the load on weight-bearing joints. However, this appears to be an over
      simplification, because obesity is also linked to OA in the hand and finger
      joints. Recent studies have shown that adipocytokine leptin is a possible link
      between obesity and OA: Leptin levels in synovial fluid are increased in obese
      patients, leptin receptor (Ob-R) is expressed in cartilage, and leptin induces
      the production of matrix metalloproteinases (MMPs), pro-inflammatory mediators
      and nitric oxide (NO) in chondrocytes. Furthermore, according to the very recent
      findings, not only leptin levels in the joint but also leptin sensitivity in the
      cartilage are enhanced in obese OA patients. The findings supporting leptin as a
      causative link between obesity and OA offer leptin as a potential target to the
      development of disease-modifying drugs for osteoarthritis (DMOAD), especially for
      obese patients. 

PMID- 24138454
TI  - The clinical value of cardiac sympathetic imaging in heart failure.
AB  - The autonomic nervous system plays an important role in the pathology of heart
      failure. The single-photon emission computed tomography tracer iodine-123
      metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of
      the predominant neurotransmitter of the sympathetic nervous system,
      norepinephrine. Also, positron emission tomography tracers are being developed
      for the same purpose. With (123) I-MIBG as a starting point, this brief review
      introduces the modalities used for cardiac sympathetic imaging. 

PMID- 24138456
TI  - Development of activity-based probes for ubiquitin and ubiquitin-like protein
      signaling pathways.
AB  - Ubiquitin and ubiquitin-like (UBL) proteins regulate a vast variety of cellular
      functions. Some UBL proteins are present in all cell types, while others are
      expressed only in certain cells or under certain environmental conditions. This
      highlights the central role of UBL systems in regulation of ubiquitous as well as
      specific cellular functions. UBL proteins share little amino acid sequence
      identity to each other, yet they share similar 3D shapes, which is exemplified by
      the beta-grasp fold. Central to UBL protein signaling pathways are UBL protein
      activating E1 enzymes that activate the C-terminus of UBL proteins for subsequent
      conjugation to the protein substrates. Due to their critical roles in biology, E1
      enzymes have been recognized as emerging drug targets to treat human diseases. In
      spite of their biological significance, however, methods to discover UBL proteins
      and to monitor the intracellular activity of E1 enzymes are lacking. Thus, there
      is a critical need for methods to evaluate the intracellular mechanisms of action
      of E1 enzyme inhibitors. Here we describe the development of a mechanism-based
      small-molecule probe, ABP1, that can be used to discover and to detect active UBL
      proteins, and to monitor the intracellular activity of E1 enzymes inside intact
      cells. The developed probe can also be used to profile the selectivity of E1
      enzyme-targeting drugs in vitro and inside intact cells. 

PMID- 24138455
TI  - 'On the surface': a qualitative study of GPs' and patients' perspectives on
      psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic, inflammatory skin disease affecting
      approximately 2% of the UK population and is currently incurable. It produces
      profound effects on psychological wellbeing and social functioning and has
      significant associated co-morbidities. The majority of patients with psoriasis
      are managed in primary care, however in-depth patient and GP perspectives about
      psoriasis management in this setting are absent from the literature. This article
      reports an in-depth study which compares and contrasts the perspectives of people
      with psoriasis and of GPs on the challenges of managing psoriasis in primary
      care. METHODS: In-depth, qualitative semi-structured interviews were conducted
      with a diverse sample of 29 people with psoriasis and 14 GPs. Interviews were
      coded using principles of Framework Analysis to enable a comparison of patient
      and practitioner perspectives on key issues and concepts arising from the data.
      RESULTS: Patients perceived GPs to be lacking in confidence in the assessment and
      management of psoriasis and both groups felt lacking in knowledge and
      understanding about the condition. While practitioners recognised that psoriasis
      has physical, emotional and social impact, they assumed patients had expertise in
      the condition and may not address these issues in consultations. This resulted in
      patient dissatisfaction and sub-optimal assessment of severity and impact of
      psoriasis by GPs. Patients and GPs recognised that psoriasis was not being
      managed as a complex long-term condition, however this appeared less problematic
      for GPs than for patients who desired a shared management with their GP
      incorporating appropriate monitoring and timely reviews. CONCLUSIONS: The
      research suggests that current routine practice for psoriasis management in
      primary care is mismatched with the expressed needs of patients. To address these
      needs, psoriasis must be recognised as a complex long-term condition involving
      exacting physical, psychological and social demands, co-morbidity and the
      development of new treatments.General practitioners need to improve both their
      knowledge and skills in the assessment and management of psoriasis. This in turn
      will facilitate management of the condition in partnership with patients.
      Commissioning multi-disciplinary services, which focus on long-term impacts on
      wellbeing and quality of life, might address current deficits in care.

PMID- 24138457
TI  - Treatment of pediatric pyogenic granulomas using beta-adrenergic receptor
      antagonists.
AB  - Propranolol and timolol are nonselective beta-adrenergic antagonists that induce
      peripheral vasoconstriction and affect angiogenic cytokines. Oral and topical
      beta-blocker therapy has become the de facto first-line treatment for complicated
      infantile hemangiomas because of its superior efficacy and tolerability. Pyogenic
      granulomas or lobular capillary hemangiomas are common acquired vascular tumors
      accounting for 0.5% of all skin nodules in children. Although they are benign
      vascular proliferations, treatment is often sought because of recurrent episodes
      of bleeding and for cosmetic considerations. Numerous treatment options are
      available, but recurrence rates are high. Noninvasive methods of treatment are
      being sought, particularly for young children. Herein we report a series of seven
      cases of cutaneous and mucosal pyogenic granulomas treated successfully using
      oral or topical beta-blockers. 

PMID- 24138458
TI  - Commentary: indefensible methods of handling missing data in clinical trials.
AB  - BACKGROUND: Literature continues to appear using inappropriate statistical
      methods when dealing with missing data in treatment trials. I regularly see last
      observation carried forward, assumed worst-case scenario, or some other static
      imputation method still being submitted and published in journals. METHODS: We
      briefly cover a few reasons why the use of more modern and defensible methods may
      not have completely saturated the literature. RESULTS: While some delay in
      complete permeation of appropriate methods is understandable, we are currently
      past the point for reasonable delay. CONCLUSIONS: Editors and reviewers should
      demand appropriate statistical methods in published literature.

PMID- 24138459
TI  - Use of biometric, hematologic, and plasma biochemical variables, and
      histopathology to assess the chronic effects of the herbicide prometryn on Common
      Carp.
AB  - BACKGROUND: Effects of acute and subchronic exposure of fish to s-triazine
      herbicides have been well documented, but data on the effects of prometryn on
      blood analytes in carp at environmentally realistic concentrations are lacking.
      OBJECTIVE: The objective of the study was to determine whether biometrics, blood
      analytes, and histopathology could serve as bioindicators in fish living in
      waters polluted by triazine. METHODS: Fish were exposed to prometryn at
      concentrations of 0.51 (reported concentration in Czech rivers), 8.0, and 80
      MUg/L for 14, 30, and 60 days. Prior to and during this period, biometrics, blood
      analytes, and histopathology were evaluated. RESULTS: After 60 days' exposure to
      8.0 and 80 MUg/L of prometryn, spleen weights (P < .05) and lactate (P < .01)
      levels were significantly lower, and concentrations of HGB (P < .01) and MHC (P <
      .01) and MCHC (P < .01) were higher, relative to controls. After 30 and 60 days'
      exposure to 0.51, 8.0, and 80 MUg/L of prometryn, AST activity, calcium,
      magnesium, and inorganic phosphate levels were lower (P < .01), while creatinine
      concentration and ALT activity were higher (P < .01) than in controls. Glucose
      was higher after exposure to 80 MUg/L after 30 and 60 days, and after 60 days'
      exposure to 8.0 MUg/L. Renal histology revealed severe hyaline degeneration of
      the epithelial cells of caudal kidney tubules in fish at all exposure levels.
      CONCLUSIONS: This study shows effects in fish blood at a concentration of 0.51
      MUg/L of prometryn, a significant finding in view of prometryn reaching a maximum
      of 4.4 MUg/L or less in European rivers. Select blood analytes, such as
      creatinine, and histologic changes in caudal kidney are potential biomarkers for
      monitoring residual triazine pesticides in Common Carp.

PMID- 24138460
TI  - Aprotinin and transfusion requirements in pediatric craniofacial surgery.
AB  - OBJECTIVE: To evaluate transfusion requirements in children receiving aprotinin
      during craniofacial surgery. BACKGROUND: Pediatric craniofacial procedures may
      involve massive blood loss. Aprotinin may decrease perioperative blood loss and
      transfusion requirements. METHODS: Patients (aged 1 month to 3 years) who had
      major reconstructive craniofacial surgery received intraoperative aprotinin (13
      patients) or placebo (13 patients). Administered colloids and blood products were
      recorded. RESULTS: Patients in the aprotinin and placebo groups had similar mean
      age, body weight, body surface area, operative time, and length of hospital stay.
      Mean volumes of total colloids (aprotinin group: 70 +/- 40 ml; and placebo group:
      120 +/- 80 ml; P <= 0.05) and packed red blood cells (aprotinin group: 380 +/- 90
      ml; and placebo group: 550 +/- 200 ml; P <= 0.004) were less in the aprotinin
      group than in the placebo group. Mean urine output during surgery was greater in
      the aprotinin group than in the placebo group (320 +/- 200 ml vs 150 +/- 70 ml,
      respectively; P <= 0.003). Mean blood urea nitrogen and serum creatinine values
      after surgery were similar between the groups. Complications of aprotinin
      included anaphylaxis (one patient) and rash (one patient); no deaths occurred.
      CONCLUSIONS: Aprotinin was associated with decreased packed red blood cell
      transfusion requirements in children undergoing craniofacial surgery, with no
      renal toxicity or death. Aprotinin is no longer available for clinical use in the
      USA because of adverse effects in adults; re-evaluation of aprotinin is warranted
      for children scheduled to undergo surgery involving potentially high blood loss.

PMID- 24138461
TI  - Safety and efficacy of propofol administered by paediatricians during procedural
      sedation in children.
AB  - AIM: The aim of this study was to determine the safety and the efficacy of
      paediatrician-administered propofol in children undergoing different painful
      procedures. METHODS: We conducted a retrospective study over a 12-year period in
      three Italian hospitals. A specific training protocol was developed in each
      institution to train paediatricians administering propofol for painful
      procedures. RESULTS: In this study, 36,516 procedural sedations were performed.
      Deep sedation was achieved in all patients. None of the children experienced
      severe side effects or prolonged hospitalisation. There were six calls to the
      emergency team (0.02%): three for prolonged laryngospasm, one for bleeding, one
      for intestinal perforation and one during lumbar puncture. Nineteen patients
      (0.05%) developed hypotension requiring saline solution administration, 128
      children (0.4%) needed O2 ventilation by face mask, mainly during upper
      endoscopy, 78 (0.2%) patients experienced laryngospasm, and 15 (0.04%) had
      bronchospasm. There were no differences in the incidence of major complications
      among the three hospitals, while minor complications were higher in children
      undergoing gastroscopy. CONCLUSION: This multicentre study demonstrates the
      safety and the efficacy of paediatrician-administered propofol for procedural
      sedation in children and highlights the importance of appropriate training for
      paediatricians to increase the safety of this procedure in children.

PMID- 24138462
TI  - Onycholysis and subungual haemorrhages in a patient with hand, foot and mouth
      disease.

PMID- 24138463
TI  - Estimation of sampling uncertainty for pesticide residues in root vegetable
      crops.
AB  - The sampling uncertainty for pesticide residues in carrots, parsley leaves and
      selected medium size crops was estimated with simple random sampling by applying
      range statistics. The primary samples taken from treated fields consisted of
      individual carrots or a handful of parsley leaves. The samples were analysed with
      QUEChERs extraction method and LCMS/MS detection with practical LOQ of 0.001
      mg/kg. The results indicate that the average sampling uncertainties estimated
      with simple random sampling and range statistics were practically the same. The
      confidence interval for the estimated sampling uncertainty decreased with the
      number of replicate samples taken from one lot and the number of lots sampled.
      The estimated relative ranges of sampling uncertainty are independent from the
      relative standard deviation of the primary samples. Consequently the conclusions
      drawn from these experiments are generally applicable. There is no optimum for
      sample size and number of lots to be tested for estimation of sampling
      uncertainty. Taking a minimum of 6 replicate samples from at least 8-12 lots is
      recommended to obtain a relative 95% range of sampling uncertainty within 50%.
      The cost of sampling/analyses, the consequences of wrong decision should also be
      taken into account when a sampling plan is prepared.

PMID- 24138464
TI  - Determination of the pyrethroid insecticide metabolite 3-PBA in plasma and urine
      samples from farmer and consumer groups in northern Thailand.
AB  - In this study, the enzyme-linked immunosorbent assays (ELISA) were modified to
      detect 3-PBA in plasma (including the adducted form) and urine among a large
      group of consumers and farmers in an agricultural area. The samples were
      collected on the same day in the morning from 100 consumers (50 females, 50
      males) and 100 farmers (50 females, 50 males) in the Fang district, Chiang Mai
      province, northern Thailand. The ELISA was very sensitive having an IC50 value of
      26.7 and 15.3 ng/mL, a limit of quantitation of 5 and 2.5 ng/mL and a limit of
      detection of 1.08 and 1.94 ng/mL for plasma and urine, respectively. These
      methods had low (< 5%) intra- and inter-assay coefficients of variation. The
      extraction technique satisfactorily eliminated the matrix effect from samples
      before ELISA analysis, yielding good recoveries (85.9-99.4% and 87.3-98.0%,
      respectively). For the volunteer study, the detection rate for plasma 3-PBA was
      24% in consumers and 42% in farmers, but the median and range values were similar
      (median 5.87 ng/mL, range 5.16-8.44 ng/mL in consumers and 6.27 ng/mL, range 4.29
      9.57 ng/mL in farmers). The rate of detection in the urine was similar (76% and
      69%, in consumers and in farmers), yet the median concentration was significantly
      higher in farmers (8.86 MUg/g creatinine in consumers vs 16.1 MUg/g creatinine in
      farmers) and the range also much wider in farmers (1.62-80.5 MUg/g creatinine in
      consumers and 0.80-256.2 MUg/g creatinine in farmers). There was no correlation
      between plasma 3-PBA and urinary 3-PBA concentrations in the study presumably
      because plasma 3-PBA is a measure of cumulative exposures while urinary 3-PBA
      reflects acute exposures. In addition, metabolism and excretion of pyrethroids
      varies by individual. Nevertheless, this study demonstrated that these volunteers
      were exposed to pyrethroids. To our knowledge, this is the first report that
      compared plasma 3-PBA and urinary 3-PBA in a large group of volunteers. The ELISA
      method provided higher sample throughput with lower cost as compared to the
      instrumental analysis.

PMID- 24138465
TI  - Biodegradation of acephate and methamidophos by a soil bacterium Pseudomonas
      aeruginosa strain Is-6.
AB  - The aim of this study was to isolate and characterize a new acephate-degrading
      bacteria from agricultural soil and to investigate its biodegradation ability and
      pathway of degradation. A bacterial strain Is-6, isolated from agriculture soil
      could completely degrade and utilize acephate as the sole carbon, phosphorus and
      energy sources for growth in M9 medium. Analysis of the 16S rRNA gene sequence
      and phenotypic analysis suggested that the strain Is-6 was belonging to the genus
      Pseudomonas aeruginosa. Strain Is-6 could completely degrade acephate (50 mg L(
      1)) and its metabolites within 96 h were identified by high-performance liquid
      chromatography (HPLC) and electron spray ionization-mass spectrometry (ESI-MS)
      analyses. When exposed to the higher concentration, the strain Is-6 showed 92%
      degradation of acephate (1000 mg L(-1)) within 7 days of incubation. It could
      also utilize dimethoate, parathion, methyl parathion, chlorpyrifos and malathion.
      The inoculation of strain Is-6 (10(7) cells g(-1)) to acephate (50 mg Kg(-1))
      treated soil resulted in higher degradation rate than in noninoculated soils.
      These results highlight the potential of this bacterium to be used in the cleanup
      of contaminated pesticide waste in the environment.

PMID- 24138466
TI  - Photocatalytic degradation of agricultural antibiotics using a UV-LED light
      source.
AB  - With a view to developing a UV-LED photocatalytic reactor for small and remote
      water systems, the degradation of three representative agriculturally produced
      contaminants, two antibiotics and an endocrine disruptor hormone, was evaluated
      in a bench 365 nm LED photoreactor using a slurry of the well-known Degussa
      P25(r) (TiO2) as photocatalyst. Use of an additional electron capture additives
      O2 and H2O2 was also assessed. Loss of the parent organic compounds was tracked
      by HPLC or UV absorbance and mineralization, where feasible, was studied with TOC
      analysis with conventional instrumentation. In all cases, degradation is
      significant with moderate light dose. Lab data suggest log reduction with light
      delivery less than 2.2 kWhr per cubic meter light delivery.

PMID- 24138467
TI  - Effects of size and moisture of rhizome on initial invasiveness ability of giant
      reed.
AB  - Studies were conducted under controlled conditions to determine growth and
      reproductive capabilities of Arundo donax L. (giant reed), a riparian invasive
      perennial plant that has spread widely. Greenhouse experiments were conducted to
      determine the influence of rhizome size and moisture content in the early
      invasiveness ability of giant reed. We tested different sizes of rhizomes:
      rhizome size of 1 cm, 3 cm, 5 cm and shredded rhizome. (fragments < 1 cm). These
      rhizomes were observed at 7, 14, 21, 28 and 35 days after planting (DAP). To test
      the effect of moisture content we used fresh rhizome fragments; rhizomes with
      moderate dehydration (50%); rhizomes with high dehydration (over 70%) with 48
      hours of rehydration and rhizomes with high dehydration (70-90%). The rhizomes
      monitored for moisture content and biomass increase were between 3 and 5 cm, and
      were observed 60 DAP. The initial size of rhizomes affected the level of
      sprouting. Rhizomes with low moisture content (due to dehydration) showed high
      increase in biomass compared with the rhizomes that had not been treated or had
      been dehydrated and then rehydrated. Our results indicated that size of rhizomes
      is related to regrowth and low moisture (dehydration) content can be overcome by
      this species. This could be linked to high rates of colonization and early
      establishment ability of this species even after mechanical treatment of
      rhizomes, in riparian environments.

PMID- 24138468
TI  - Managing Salmonella Typhimurium and Escherichia coli O157:H7 in soil with
      hydrated lime - An outdoor study in lysimeters and field plots.
AB  - An outbreak of Salmonella Typhimurium or E. coli O157:H7 among domestic animals
      can have great financial consequences for an animal enterprise but also be a
      threat for public health as there is a risk for transmission of the infection
      through the environment. In order to minimize disease transmission, it is
      important to treat not only the affected animals but also the areas on which they
      have been kept. In the present study, the effect of hydrated lime as a treatment
      for Salmonella Typhimurium or E. coli O157:H7 contaminated soil was investigated.
      The study was performed outdoors, in a lysimeter system and in field plots. The
      soils were spiked with Salmonella Typhimurium and/or E. coli O157:H7 and hydrated
      lime was added at three different concentrations (0.5, 1 and 2%). Sampling was
      performed over one month, and the levels of bacteria were analyzed by standard
      culture methods. In addition, the soil pH was monitored throughout the study. The
      results showed that application of 0.5-1 kg hydrated lime per m(2) reduced both
      Salmonella Typhimurium and E. coli O157:H7 numbers to below the detection limit
      (2 log10 CFU g-1 soil) in 3-7 days. Lower application rates of hydrated lime did
      not reduce pathogen numbers in the lysimeter study, but in the field plots no E.
      coli O157:H7 was detected at the end of the four-week study period regardless of
      hydrated lime application. A recommended strategy for treating a Salmonella
      Typhimurium or E. coli O157:H7 contaminated soil could therefore be to monitor
      the pH over the time of treatment and to repeat hydrated lime application if a
      decrease in pH is observed.

PMID- 24138469
TI  - Wheat straw biomass: a resource for high-value chemicals.
AB  - Two methods are proposed for increasing the commercial value of wheat straw based
      on its chemical constituents. The first method involves the determination and
      extraction of the major organic components of wheat straw, and the second
      involves those found and extracted in the aqueous and viscous biooils derived
      from the straw by fast pyrolysis. We used pyrolysis-field ionization mass
      spectrometry to identify the fine chemicals, which have high commercial values.
      The most abundant organic compounds in the wheat straw and biooil used as
      precursors for green chemicals are N-heterocycles (16 to 29% of the Total Ion
      Intensities, TII) and fatty acids (19 to 26% of TIIs), followed by phenols and
      lignins (12 to 23% of TIIs). Other important precursors were carbohydrates and
      amino acids (1 to 8% TIIs), n-alkyl benzenes (3 to 5% of TIIs), and diols (4 to
      9% TIIs). Steroids and flavonoids represented 1 to 5% of TIIs in the three
      materials. Examples of valuable chemical compounds that can be extracted from the
      wheat straw and biooils are m/z 256, 270, 278, 280, 282 and 284, which are the n
      C16 and n-C17 fatty acids respectively, and the C18:3, C18:2 and C18:1
      unsaturated fatty acids. In particular, the C18:2 (linoleic acid) is present at a
      concentration of 1.7% of TIIs. Pyrazole, pyrazine, pyridine, indoles, quinolines,
      carbazoles, and their identified derivatives are found in relatively high
      concentrations (1 to 8% of TIIs). Other useful compounds are sterols such as m/z
      412 (stigmasterol), m/z 414 (beta-sitosterol), and steroids such m/z 394
      (stigmastatriene), m/z 398 (stigmastene) and m/z 410 (stigmastadienone). Relative
      to the wheat straw, the relative concentration of all flavonoids such as m/z 222
      (flavone) and m/z 224 (flavonone) doubled in the biooils. The conversion of wheat
      straw by fast pyrolysis, followed by chemical characterization with mass
      spectrometry, and extraction of fine chemicals, opens up new possibilities for
      increasing the monetary value of crop residues. 

PMID- 24138470
TI  - Early systemic cellular immune response in children and young adults receiving
      decellularized fresh allografts for pulmonary valve replacement.
AB  - OBJECTIVES: The longevity of homografts is determined by the activation of the
      recipients' immune system resulting from allogenic antigen exposition. Fresh
      decellularized pulmonary homografts (DPH) have shown promising early results in
      pulmonary valve replacement in children and young adults and could potentially
      avoid significant activation of the immune system, as more than 99% of the donor
      DNA is removed during the decellularization process. While the humoral immune
      response to decellularized allografts has been studied, detailed information on
      the more significant cellular immune response is currently lacking. METHODS AND
      RESULTS: Peripheral blood samples were obtained from patients undergoing
      pulmonary valve replacement with DPH before, after, and for approximately 3 years
      after implantation. Absolute counts and percentages of mature T- (CD3(+)), B-
      (CD19(+)), and natural killer- (CD16(+)/CD56(+)) cells, as well as T helper-
      (CD4(+)) and cytotoxic T-cell- (CD8(+)) subsets, were determined by fluorescence
      activated cell sorting (FACS). Between May 2009 and September 2013, 199 blood
      samples taken from 47 patients with a mean age at DPH implantation of 16.6+/-10.8
      years were analyzed. The hemodynamic performance of DPH was excellent in all but
      one patient, and no valve-related deaths or conduit explantations were observed.
      The short-term follow up revealed a significant postoperative decrease in cell
      counts of most subtypes with reconstitution after 3 months. Continued assessment
      did not show any significant deviations in cell counts from their baseline
      values. CONCLUSION: The absence of cellular immune response in patients receiving
      DPH supports the concept that decellularization can provide a basis for
      autologous regeneration.

PMID- 24138472
TI  - Real-time infrared thermography detection of magnetic nanoparticle hyperthermia
      in a murine model under a non-uniform field configuration.
AB  - PURPOSE: Magnetic nanoparticle hyperthermia consists of an increase of the
      temperature of magnetic nanoparticles (heat centres) due to the interaction of
      their magnetic moments with an alternating magnetic field. In vivo experiments
      using this method usually use a few fibre-optic thermometers inserted in the
      animal body to monitor the heat deposition. As a consequence, only a few points
      of the 3D temperature distribution can be monitored by this invasive procedure.
      It is the purpose of this work to show that non-invasive infrared thermography is
      able to detect, in real time, magnetic nanoparticle hyperthermia as well as
      monitor the harmful field-induced eddy currents in a murine model with a
      subcutaneous tumour. This surface temperature measurement method has the
      potential to give information about the intratumoral temperature. MATERIALS AND
      METHODS: The non-invasive magnetic hyperthermia experiments were performed at 300
      kHz in non-uniform field configuration conditions in healthy mice and murine
      tumour induced by sarcoma S180. A soft ferrite-based biocompatible magnetic
      colloid consisting of manganese-ferrite nanoparticles surface-coated with citric
      acid were used in the experiments, which were extensively characterised by
      several techniques (transmission electron microscopy (TEM), X-ray diffraction
      (XRD), vibrating sample magnetometer (VSM)). The amplitude of the alternating
      magnetic fields was obtained from measurements using an AC field probe at similar
      experimental conditions. The temperature measurements were obtained from an
      infrared thermal camera and a fibre-optic thermometer. RESULTS: Three-minute
      magnetic hyperthermia experiments revealed surface temperature increase as high
      as 11  degrees K in healthy and (5  degrees K in S180 tumour) animals when
      injecting subcutaneously 2 mg of magnetic nanoparticles (86 MUL of magnetic
      fluid), in contrast to around 1.5  degrees K (for healthy) and 2.5  degrees K
      (for cancerous) animals in experiments without the colloid due to field-induced
      eddy currents at the animal surface. The thermographic temperature measurements
      were found to agree with the fibre-optic measurements within a 5% error, and were
      associated with the skin emissivity angle of dependence in the experimental set
      up. On the other hand, a 30-min magnetic nanoparticle hyperthermia revealed
      surface temperature increases as high as 12  degrees K close to the injection
      site, while above 2-3 cm no significant temperature increase was observed.
      Curiously, the intratumoral temperature, monitored by a fibre-optic sensor, was
      found to be almost the same as the thermal camera surface temperature after
      achieving an equilibrium temperature regime. From the observed isotherms at the
      animal surface, using an analytical heat conduction model, taking into account
      surface conductance, we estimate a magnetic heating power of 0.45 W/cm(3) and a
      specific loss power (SLP) of 85 W/g for a field of the order of only 10 kA/m at
      the injection site region. CONCLUSIONS: The results indicate that infrared
      thermography may be a promising tool for both early cancer detection and for
      hyperthermia treatment (at least for subcutaneous tumours), since the method
      permits access to information about the intratumoral temperature during a real
      time magnetic hyperthermia as well as to estimate the in vivo nanoparticles SLP.

PMID- 24138473
TI  - Identification of genome-wide single nucleotide polymorphisms in allopolyploid
      crop Brassica napus.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common type of
      genetic variation. Identification of large numbers of SNPs is helpful for genetic
      diversity analysis, map-based cloning, genome-wide association analyses and
      marker-assisted breeding. Recently, identifying genome-wide SNPs in allopolyploid
      Brassica napus (rapeseed, canola) by resequencing many accessions has become
      feasible, due to the availability of reference genomes of Brassica rapa (2n = AA)
      and Brassica oleracea (2n = CC), which are the progenitor species of B. napus (2n
      = AACC). Although many SNPs in B. napus have been released, the objective in the
      present study was to produce a larger, more informative set of SNPs for large
      scale and efficient genotypic screening. Hence, short-read genome sequencing was
      conducted on ten elite B. napus accessions for SNP discovery. A subset of these
      SNPs was randomly selected for sequence validation and for genotyping efficiency
      testing using the Illumina GoldenGate assay. RESULTS: A total of 892,536 bi
      allelic SNPs were discovered throughout the B. napus genome. A total of 36,458
      putative amino acid variants were located in 13,552 protein-coding genes, which
      were predicted to have enriched binding and catalytic activity as a result. Using
      the GoldenGate genotyping platform, 94 of 96 SNPs sampled could effectively
      distinguish genotypes of 130 lines from two mapping populations, with an average
      call rate of 92%. CONCLUSIONS: Despite the polyploid nature of B. napus, nearly
      900,000 simple SNPs were identified by whole genome resequencing. These SNPs were
      predicted to be effective in high-throughput genotyping assays (51% polymorphic
      SNPs, 92% average call rate using the GoldenGate assay, leading to an estimated
      >450 000 useful SNPs). Hence, the development of a much larger genotyping array
      of informative SNPs is feasible. SNPs identified in this study to cause non
      synonymous amino acid substitutions can also be utilized to directly identify
      causal genes in association studies.

PMID- 24138474
TI  - Surfing transcriptomic landscapes. A step beyond the annotation of chromosome 16
      proteome.
AB  - The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of
      Chr16 and data analysis as one of its priorities. Precise annotation of
      Chromosome 16 proteins according to C-HPP criteria is presented. Moreover, Human
      Body Map 2.0 RNA-Seq and Encyclopedia of DNA Elements (ENCODE) data sets were
      used to obtain further information relative to cell/tissue specific chromosome 16
      coding gene expression patterns and to infer the presence of missing proteins.
      Twenty-four shotgun 2D-LC-MS/MS and gel/LC-MS/MS MIAPE compliant experiments,
      representing 41% coverage of chromosome 16 proteins, were performed. Furthermore,
      mapping of large-scale multicenter mass spectrometry data sets from CCD18, MCF7,
      Jurkat, and Ramos cell lines into RNA-Seq data allowed further insights relative
      to correlation of chromosome 16 transcripts and proteins. Detection and
      quantification of chromosome 16 proteins in biological matrices by SRM procedures
      are also primary goals of the SpHPP. Two strategies were undertaken: one focused
      on known proteins, taking advantage of MS data already available, and the second,
      aimed at the detection of the missing proteins, is based on the expression of
      recombinant proteins to gather MS information and optimize SRM methods that will
      be used in real biological samples. SRM methods for 49 known proteins and for
      recombinant forms of 24 missing proteins are reported in this study. 

PMID- 24138475
TI  - "What kind of general practitioner do I need for smoking cessation?" Results from
      a qualitative study in Poland.
AB  - BACKGROUND: Cigarette smoking remains the leading preventable cause of death and
      disease. Thus, all activities aiming to reduce smoking play an important role in
      improving population health. The positive role of the general practitioner (GP)
      in smoking cessation could increase the success rate for quitting smoking, if
      compared with unassisted cessation. The aim of this study was to determine what
      kind of general practitioner smokers need in order to stop smoking. METHODS: Four
      focus groups with 12 current and 12 former smokers (aged 20-59, 11 women and 13
      men), were arranged in the city of Torun, Poland, with a view to describe their
      opinions on the GP's role in smoking cessation. The data were subjected to
      descriptive qualitative content analysis. RESULTS: Two major themes emerged in
      the analysis: the smokers' positive and negative experiences of the GP in smoking
      cessation and their expectations regarding the role of the GP in smoking
      cessation. The first theme embraced the following subthemes: (1) GP's passivity,
      (2) routine questions about the patient's smoking during the visit, (3) lack of
      time during the visit, and (4) the role model of the GP in smoking cessation.
      Within the second theme, the respondents identified the following subthemes: (1)
      bringing up the topic of smoking cessation, even in situations when the patient
      is unprepared for this; (2) the necessity of a tailored approach to the patient;
      (3) access to information and evidence confirming the harms of smoking tobacco;
      (4) prescription of pharmacological and other treatment; and (5) referral to
      specialists in smoking cessation. CONCLUSIONS: Patients expect their GP to
      actively participate in smoking cessation through a more tailored approach to the
      patient's needs. The patients' experiences did not match their expectations: the
      smokers rarely got advice on smoking cessation from their GPs. Finally, they
      emphasized the importance of the GP as a role model in smoking cessation.

PMID- 24138476
TI  - Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs
      treated with vincristine sulfate.
AB  - Secondary dyserythropoiesis has been associated with vincristine administration
      in dogs. Evaluation of bone marrow aspirates for the presence of morphologic
      abnormalities in the erythroid lineage aids in the diagnosis. However,
      morphologic features of circulating erythroid precursors in these cases have not
      been described previously. The purpose of this report was to describe the
      cytologic features of dyserythropoiesis in peripheral blood and also bone marrow
      smears in a case series of dogs with immune-mediated thrombocytopenia (IMT)
      treated with vincristine sulfate. Nineteen dogs receiving vincristine for
      treatment of IMT were identified by retrospectively searching a computerized
      medical record system. There were 5 dogs that had dysplastic erythroid precursors
      in peripheral blood smears within 7 days of vincristine treatment. Two of those 5
      dogs also had evidence for erythrodysplasia in modified Wright's-stained bone
      marrow smears obtained postvincristine administration. Morphologic changes
      included bizarre or inappropriate mitotic figures, abnormal nuclear
      configurations (fragmentation, elongation, indentation, and binucleation),
      atypical nuclear remnants (Howell-Jolly bodies), or nuclear and cytoplasmic
      asynchrony within the erythroid precursors. A brief review of the literature with
      discussion of the etiologies for dyserythropoiesis is provided. The
      dyserythropoiesis was clinically insignificant in all 5 cases and resolved.
      However, pathologists and clinicians should be aware of these potential findings
      to prevent misdiagnosis of other conditions.

PMID- 24138477
TI  - pH dictates the release of hydrophobic drug cocktail from mesoporous
      nanoarchitecture.
AB  - Combination therapy has been a norm in clinical practice to effectively treat
      cancer. Besides polytherapy, nowadays, smart and nanobased drug carriers are
      extensively being explored to deliver drugs according to pathophysiological
      environment of diseases. In this regard, herein we designed intelligent
      mesoporous architecture, incorporating both combinational therapy with smart
      nanotechnology, to simultaneously deliver two highly hydrophobic chemotherapeutic
      drugs in response to extracellular and/or intracellular acidic environ of tumor.
      Novelty of the system lies in the employment of acid responsive ZnO QDs to clog
      not only the nanochannels of mesoporous silica, encapsulating one hydrophobic
      drug, but also exploitation of chelate forming propensity of another hydrophobic
      drug (curcumin) to load a significant quantity onto the surface of ZnO nanolids.
      Cell viability results revealed an extraordinarily high cytotoxic efficiency of
      that lethal drug cocktail even at a concentration as low as 3 MUg/mL nanocarrier.
      We envision that this sophisticated nanocarrier, which utilizes both interior
      pore and exterior surface of nanolids for loading different hydrophobic guest
      molecules and their subsequent acid responsive release, will undoubtedly,
      illustrates its remarkable potential in targeted chemotherapy. 

PMID- 24138478
TI  - Crusted scabies misdiagnosed as erythrodermic psoriasis in a 3-year-old girl with
      down syndrome.
AB  - Scabies is a highly contagious infestation with the Sarcoptes scabiei var hominis
      mite. The variety of clinical presentations make timely, accurate diagnosis
      problematic. We report the case of a 3-year-old girl with Down syndrome and
      crusted scabies initially misdiagnosed as erythrodermic psoriasis. 

PMID- 24138479
TI  - Selective nanovector mediated treatment of activated proinflammatory
      microglia/macrophages in spinal cord injury.
AB  - Much evidence shows that acute and chronic inflammation in spinal cord injury
      (SCI), characterized by immune cell infiltration and release of inflammatory
      mediators, is implicated in development of the secondary injury phase that occurs
      after spinal cord trauma and in the worsening of damage. Activation of
      microglia/macrophages and the associated inflammatory response appears to be a
      self-propelling mechanism that leads to progressive neurodegeneration and
      development of persisting pain state. Recent advances in polymer science have
      provided a huge amount of innovations leading to increased interest for polymeric
      nanoparticles (NPs) as drug delivery tools to treat SCI. In this study, we tested
      and evaluated in vitro and in vivo a new drug delivery nanocarrier: minocycline
      loaded in NPs composed by a polymer based on poly-epsilon-caprolactone and
      polyethylene glycol. These NPs are able to selectively target and modulate,
      specifically, the activated proinflammatory microglia/macrophages in subacute
      progression of the secondary injury in SCI mouse model. After minocycline-NPs
      treatment, we demonstrate a reduced activation and proliferation of
      microglia/macrophages around the lesion site and a reduction of cells with round
      shape phagocytic-like phenotype in favor of a more arborized resting-like
      phenotype with low CD68 staining. Treatment here proposed limits, up to 15 days
      tested, the proinflammatory stimulus associated with microglia/macrophage
      activation. This was demonstrated by reduced expression of proinflammatory
      cytokine IL-6 and persistent reduced expression of CD68 in traumatized site. The
      nanocarrier drug delivery tool developed here shows potential advantages over the
      conventionally administered anti-inflammatory therapy, maximizing therapeutic
      efficiency and reducing side effects. 

PMID- 24138480
TI  - The effects of exercise training on arterial stiffness in coronary artery disease
      patients: a state-of-the-art review.
AB  - The purpose of this state-of-the-art review was to examine the effects of
      exercise training on arterial stiffness (AS) in patients with coronary artery
      disease (CAD). A PubMed and SCOPUS literature search was conducted up to March of
      2013. Two authors performed the selection of the studies and the subsequent data
      extraction (e.g. information on study design, exercise programme characteristics
      and outcome measures). Of 34 papers identified, only five studies met the
      inclusion criteria, with no one being a randomized controlled trial. Within the
      selected studies, the sample size varied between 28 and 119 patients, with mean
      ages ranging from 48 to 67 years old in patients with CAD after an acute
      myocardial infarction, coronary artery bypass graft or percutaneous transluminal
      coronary angioplasty. Although all studies utilized the aerobic exercise mode,
      the other characteristics of the exercise programmes varied largely between the
      studies: programme length (from 6 to 20 weeks), exercise duration (15-20 to 50
      min) and exercise intensity, which was based on heart rate reserve (40 to 85%) or
      heart rate at anaerobic threshold or ventilatory threshold. All the three studies
      evaluating pulse wave velocity, as well as one of two studies that assessed the
      augmentation index, reported significant reductions on those variables after
      exercise training. Results indicated that the majority of the AS and related
      measures improved after the different exercise training programmes. However,
      these results need to be confirmed in future randomized clinical studies
      controlling potential confounders.

PMID- 24138481
TI  - Clinical trials of viral therapy for malignant gliomas.
AB  - Despite recent scientific advances in the understanding of the biology of
      malignant gliomas, there has been little change in the overall survival for this
      devastating disease. New and innovative treatments are under constant
      investigation. Starting in the 1990s, there was an interest in using viral
      therapeutics for the treatment of malignant gliomas. Multiple strategies were
      pursued, including oncolytic viral therapy, enzyme/pro-drug combinations and gene
      transfer with viral vectors. Multiple Phase I and II trials demonstrated the
      safety of these techniques, but clinically showed limited efficacy. However, this
      led to a better understanding of the pitfalls of viral therapy and encouraged the
      development of new approaches and improved delivery methods. Here we review the
      prior and ongoing clinical trials of viral therapy for gliomas, and discuss how
      novel strategies are currently being utilized in clinical trials. 

PMID- 24138482
TI  - A DNA double-strand break kinetic rejoining model based on the local effect
      model.
AB  - We report here on a DNA double-strand break (DSB) kinetic rejoining model
      applicable to a wide range of radiation qualities based on the DNA damage pattern
      predicted by the local effect model (LEM). In the LEM this pattern is derived
      from the SSB and DSB yields after photon irradiation in combination with an
      amorphous track structure approach. Together with the assumption of a giant-loop
      organization to describe the higher order chromatin structure this allows the
      definition of two different classes of DSB. These classes are defined by the
      level of clustering on a micrometer scale, i.e., "isolated DSB" (iDSB) are
      characterized by a single DSB in a giant loop and "clustered DSB" (cDSB) by two
      or more DSB in a loop. Clustered DSB are assumed to represent a more difficult
      challenge for the cell repair machinery compared to isolated DSB, and we thus
      hypothesize here that the fraction of isolated DSB can be identified with the
      fast component of rejoining, whereas clustered DSB are identified with the slow
      component of rejoining. The resulting predicted bi-exponential decay functions
      nicely reproduce the experimental curves of DSB rejoining over time obtained by
      means of gel electrophoresis elution techniques as reported by different labs,
      involving different cell types and a wide spectrum of radiation qualities. New
      experimental data are also presented aimed at investigating the effects of the
      same ion species accelerated at different energies. The results presented here
      further support the relevance of the proposed two classes of DSB as a basis for
      understanding cell response to ion irradiation. Importantly the density of DSB
      within DNA giant loops of around 2 Mbp size, i.e., on a micrometer scale, is
      identified as a key parameter for the description of radiation effectiveness. 

PMID- 24138483
TI  - OH radicals from the indirect actions of X-rays induce cell lethality and mediate
      the majority of the oxygen enhancement effect.
AB  - We examined OH radical-mediated indirect actions from X irradiation on cell
      killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic
      and hypoxic conditions, and compared the contribution of direct and indirect
      actions under both conditions. The contribution of indirect action on cell
      killing can be estimated from the maximum degree of protection by
      dimethylsulfoxide, which suppresses indirect action by quenching OH radicals
      without affecting the direct action of X rays on cell killing. The contributions
      of indirect action on cell killing of CHO cells were 76% and 50% under oxic and
      hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%,
      respectively. Therefore, the indirect action on cell killing was enhanced by
      oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios
      (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 +/
      0.15 and 2.76 +/- 0.08, respectively. OERs were evaluated separately for
      indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and
      4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value
      of ~3 is best understood as the average of the OER values for both indirect and
      direct actions. These results imply that both indirect and direct actions on cell
      killing require oxygen for the majority of lethal DNA damage, however, oxygen
      plays a larger role in indirect than for direct effects. Conversely, the lethal
      damage induced by the direct action of X rays are less affected by oxygen
      concentration. 

PMID- 24138484
TI  - Severity of deliberate acute baclofen poisoning: a nonconcurrent cohort study.
AB  - Interest in high-dose baclofen treatment for alcohol dependence has increased
      over the past few years. In the meantime, the rate of acute baclofen poisoning
      has increased and life-threatening cases have been reported. Thus, severity of
      acute poisoning could lessen the benefit of baclofen treatment. Our aim was to
      evaluate the severity of acute baclofen poisoning independently of confounders
      and to assess whether severity is correlated with the reported ingested dose. We
      prospectively included consecutive patients with acute and deliberate baclofen
      overdose and compared them with gender and age-matched patients from a
      retrospective cohort of common acute medicine self-poisoning. The primary end
      point was the adjusted risk ratio of mechanical ventilation. We also analysed the
      lengths of mechanical ventilation and risks of aspiration pneumonitis and
      convulsions. We finally examined the correlation between the supposed reported
      ingested dose and the severity of poisoning. Fourteen baclofen-poisoned patients
      were included and matched to 56 poisoned patients. Median age was 45 y/o (40-58),
      and men comprised 43% of patients. In logistic regression, the adjusted risk
      ratio of mechanical ventilation was 7.9 (1.4-43.5; p=0.02) for baclofen-treated
      patients. Aspiration pneumonitis was more frequent in baclofen-treated patients
      (29% versus 2%; p=0.005), and the length of mechanical ventilation was
      significantly correlated with the reported ingested dose of baclofen (Spearman
      coefficients: 0.48; p<0.001). Our results show that acute baclofen poisoning is
      more severe than other acute medicine overdoses, and severity seems to be
      correlated with the ingested dose of baclofen. These results raise some questions
      about the safety of high-dose baclofen treatment for alcohol dependence.

PMID- 24138485
TI  - Barriers to HIV care for women of color living in the Southeastern US are
      associated with physical symptoms, social environment, and self-determination.
AB  - HIV-infected women of color (WOC) face particular barriers to accessing HIV
      medical care. To understand the impact of physical symptoms, social support, and
      self-determination on barriers to care, we interviewed HIV-infected women of
      color. HIV-infected WOC (N=141), attending an academic infectious disease clinic
      for HIV care in North Carolina, completed the Barriers to Care scale and were
      categorized as reporting a history of low (less than four of eleven barriers) or
      high (five or more) barriers to care. Binomial regression was used to estimate
      prevalence ratios and risk differences of reported barriers to care and its
      correlates such as depression, anxiety, illness-severity, psychological abuse,
      social support, treatment-specific social support, and self-determination
      (autonomy, relatedness, competency). A lower risk of reporting five or more
      barriers to care was associated with higher levels of autonomy (PR=0.93, 95% CI:
      0.89, 0.96), relatedness (PR=0.92, 95% CI: 0.89, 0.94), competency (PR=0.93, 95%
      CI: 0.87, 0.98), and social support (PR=0.24, 95% CI: 0.81, 0.81). Depression,
      illness severity, and psychological abuse were associated with a greater risk of
      having five or more barriers to care. There are multiple social and psychological
      factors that contribute to perceived barriers to HIV care among WOC in the
      southeastern USA. Interventions that promote social support and increase
      individual self-determination have the potential to improve access to HIV care
      for WOC.

PMID- 24138486
TI  - The impact of anticipated HIV stigma on delays in HIV testing behaviors: findings
      from a community-based sample of men who have sex with men and transgender women
      in New York City.
AB  - Treatment as prevention (TaSP) is a critical component of biomedical
      interventions to prevent HIV transmission. However, its success is predicated on
      testing and identifying undiagnosed individuals to ensure linkage and retention
      in HIV care. Research has examined the impact of HIV-associated stigma on HIV
      positive individuals, but little work has explored how anticipated HIV stigma-the
      expectation of rejection or discrimination against by others in the event of
      seroconversion-may serve as a barrier to HIV testing behaviors. This study
      examined the association between anticipated stigma and HIV testing behaviors
      among a sample of 305 men who have sex with men (MSM) and transgender women
      living in New York City. Participants' mean age was 33.0; 65.5% were
      racial/ethnic minority; and 50.2% earned <$20,000 per year. Overall, 32% of
      participants had not had an HIV test in the past 6 months. Anticipated stigma was
      negatively associated with risk perception. In multivariate models, anticipated
      stigma, risk perception, and younger age were significant predictors of HIV
      testing behaviors. Anti-HIV stigma campaigns targeting HIV-negative individuals
      may have the potential to significantly impact social norms around HIV testing
      and other biomedical strategies, such pre-exposure prophylaxis, at a critical
      moment for the redefinition of HIV prevention.

PMID- 24138487
TI  - HIV testing among immigrant sexual and gender minority Latinos in a US region
      with little historical Latino presence.
AB  - Immigrant sexual and gender minority Latinos constitute a vulnerable subgroup
      about which little is known. We examined HIV testing among 190 such Latinos
      recruited via respondent-driven sampling in North Carolina, a state with little
      historical Latino presence but recent, rapid growth of this population. Sixty
      eight percent reported an HIV test in the past year, and nearly half reported
      multiple HIV tests. Concern for their health was the most frequent reason for
      seeking an HIV test. Reasons not to get tested included fear of a positive test,
      previous HIV tests, worry that test results might be reported to the government,
      and concerns that others might treat the person differently if found to be HIV
      positive. In a multiple variable model, correlates of HIV testing included age,
      educational attainment, HIV stigma, comfort with sexual orientation, and previous
      STD diagnoses. Among participants reporting anal sex, consistent condom use was
      associated with HIV testing, suggesting that protective behaviors may co-occur.
      These findings may inform the development of more efficacious interventions to
      increase HIV testing among this subgroup.

PMID- 24138489
TI  - Is dipole moment a valid descriptor of excited state's charge-transfer character?
AB  - In the ongoing discussion on excited states of the pentacene crystal, dipole
      moment values have been recently invoked to gauge the CT admixture to excited
      states of Frenkel parentage in a model cluster. In the present paper, a simple
      dimer model is used to show that, in general, the dipole moment is not a valid
      measure of the CT contribution. This finding eliminates some apparent
      disagreement between the computational results published by different research
      groups. The implications of our results and other related aspects of cluster-type
      quantum chemistry calculations are discussed in the context of the standing
      literature dispute concerning the mechanism of singlet fission in the pentacene
      crystal, notably the role of charge transfer contributions vs the involvement of
      an excimer-like doubly excited intermediate (D state). 

PMID- 24138488
TI  - Factors associated with smoking in HIV-infected patients and potential barriers
      to cessation.
AB  - Smoking is common in patients with HIV and is associated with increased morbidity
      and mortality. With the goal of targeting future cessation interventions, we
      sought to identify factors associated with smoking status, readiness and
      confidence in cessation, and success in quitting. As part of a larger study in
      New York City assessing predictors of chronic obstructive pulmonary disease
      (COPD), we enrolled HIV-infected subjects at least 35 years of age without known
      asthma or COPD. Current smokers received detailed tobacco history, and smoking
      status was assessed by chart review at 3 and 6 months post-enrollment. Two
      hundred subjects were enrolled (29% current smokers, 31.5% never smokers, 39.5%
      former smokers, mean age of 49, 84% male, 64% had AIDS, and 97% were receiving
      antiretroviral therapy). Current smokers had higher unemployment and increased
      rates of other substance use than former smokers or never smokers. In
      multivariate analysis, being unemployed and having used inhalant drugs were
      associated with current smoking. Substance abuse history was not correlated with
      readiness to quit or patient estimated cessation. Lower education was associated
      with decreased readiness to quit. Follow-up smoking status for baseline current
      smokers was available for 47/58 enrollees at 6 months; 4 (9%) stopped smoking
      completely, and 17 (36%) decreased the number of packs-per-day. Smoking and
      concomitant substance abuse is common in HIV, and special attention should be
      given to this issue, in addition to a patient's readiness to quit, when
      implementing tobacco cessation protocols, especially in busy urban HIV care
      centers.

PMID- 24138490
TI  - Groundwater flow cycling between a submarine spring and an inland fresh water
      spring.
AB  - Spring Creek Springs and Wakulla Springs are large first magnitude springs that
      derive water from the Upper Floridan Aquifer. The submarine Spring Creek Springs
      are located in a marine estuary and Wakulla Springs are located 18 km inland.
      Wakulla Springs has had a consistent increase in flow from the 1930s to the
      present. This increase is probably due to the rising sea level, which puts
      additional pressure head on the submarine Spring Creek Springs, reducing its
      fresh water flow and increasing flows in Wakulla Springs. To improve
      understanding of the complex relations between these springs, flow and salinity
      data were collected from June 25, 2007 to June 30, 2010. The flow in Spring Creek
      Springs was most sensitive to rainfall and salt water intrusion, and the flow in
      Wakulla Springs was most sensitive to rainfall and the flow in Spring Creek
      Springs. Flows from the springs were found to be connected, and composed of three
      repeating phases in a karst spring flow cycle: Phase 1 occurred during low
      rainfall periods and was characterized by salt water backflow into the Spring
      Creek Springs caves. The higher density salt water blocked fresh water flow and
      resulted in a higher equivalent fresh water head in Spring Creek Springs than in
      Wakulla Springs. The blocked fresh water was diverted to Wakulla Springs,
      approximately doubling its flow. Phase 2 occurred when heavy rainfall resulted in
      temporarily high creek flows to nearby sinkholes that purged the salt water from
      the Spring Creek Springs caves. Phase 3 occurred after streams returned to base
      flow. The Spring Creek Springs caves retained a lower equivalent fresh water head
      than Wakulla Springs, causing them to flow large amounts of fresh water while
      Wakulla Springs flow was reduced by about half. 

PMID- 24138491
TI  - Inter-annual variation of persistent organic pollutants (POPS) in an Antarctic
      top predator Arctocephalus gazella.
AB  - Persistent organic pollutants (POPs), contaminants that may bioaccumulate in
      upper trophic level organisms, were detected in the milk of a top predator, the
      Antarctic fur seal (Arctocephalus gazella). Multiparous females had significantly
      lower concentrations of certain POPs (trans-nonachlor, p,p'-DDE, and several
      PCBs) in their milk than primiparous females, likely due to the annual
      lactational transfer of the POP burden from mother to pup. Furthermore, there
      were significant interannual differences in POP concentrations in multiparous
      females' milk from five breeding seasons between 2000 and 2011. Decreasing trends
      in concentrations of certain POPs over the recent decade coincide with declining
      global emissions, yet atmospheric concentrations in the Antarctic are not always
      consistent with global trends, suggesting that additional factors may contribute
      to temporal trends of POPs in fur seals. Climate shifts and corresponding
      availability of krill over the past decade were not consistent with trends
      observed in POP concentrations in fur seal milk, suggesting that climate may not
      be a key factor. Additional mechanisms, such as variability in the geographic
      ranges of individual seals during overwintering migrations are discussed and
      should be explored further. 

PMID- 24138492
TI  - Isolated ultrafiltration: its origin and early development.

PMID- 24138493
TI  - The balancing act of timing the intra-aortic balloon pump.

PMID- 24138494
TI  - Investigation of risks for cerebral embolism associated with the hemodynamics of
      cardiopulmonary bypass cannula: a numerical model.
AB  - Cerebral emboli originating in the ascending aorta are a major cause of
      noncardiac complications following cardiac surgery. The hemodynamics of the
      aortic cannula has been proven to play a significant role in emboli generation
      and distribution. The aim of the current study was to perform a thorough
      numerical investigation in order to examine the effect of the design and
      orientation of the cannula used during cardiopulmonary bypass on the risk to
      develop cerebral embolism. Hemodynamic analyses compared numerical models of 27
      cases consisting of six different cannula orientations, four aortic anatomies,
      and three cannula designs. The cannula designs included a straight-tip (ST)
      cannula, a moderately curved tip cannula (TIP1 ), and a sharp-angle curved
      cannula (TIP2 ). Outcome measures included hemodynamic parameters such as
      emanating jet velocity, jet velocity drop, maximal shear stress, aortic wall
      reaction, emboli pathlines and distribution between upper and lower vessels, and
      stagnation regions. Based on these parameters, the risks for hemolysis,
      atheroembolism, and cerebral embolism were evaluated and compared. On one hand,
      the jet emerging from the ST cannula generated large wall-shear stress at the
      aortic wall; this may have triggered the erosion and distribution of embolic
      atheromatous debris from the aortic arch. On the other hand, it diverted more
      emboli from the clamp region to the descending aorta and thus reduced the risk
      for cerebral embolism. The TIP1 cannula demonstrated less shear stress on the
      aortic wall and diverted more emboli from the clamp region toward the upper
      vessels. The TIP2 cannula exhibited a stronger emanating jet, higher shear stress
      inside the cannula, and highly disturbed flow, which was more stagnant near the
      clamp region. Current findings support the significant impact of the cannula
      design and orientation on emboli generation and distribution. Specifically, the
      straight tip cannula demonstrated a reduced risk of cerebral embolism, which may
      be pivotal in the clinical setting. 

PMID- 24138497
TI  - Plerixafor on-demand combined with chemotherapy and granulocyte colony
      stimulating factor: significant improvement in peripheral blood stem cells
      mobilization and harvest with no increase in costs.
AB  - To date, no prospective study on Plerixafor 'on-demand' in combination with
      chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported.
      We present an interim analysis of the first prospective study in which Plerixafor
      was administered on-demand in patients affected by multiple myeloma and lymphoma
      who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine,
      cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred
      and two patients were evaluable for response. A cohort of 240 patients receiving
      the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize
      CD34(+) cells in peripheral blood was reduced by 'on-demand' strategy compared to
      conventional mobilization; from 13.0 to 3.0% (P = 0.004). Failure to harvest
      CD34(+) cells 2 * 10(6) /kg decreased from 20.9 to 4.0% (P = 0.0001). The on
      demand Plerixafor strategy also resulted in a lower rate of mobilization failure
      (P = 0.03) and harvest failure (P = 0.0008) when compared to a 'bias-adjusted set
      of controls'. Evaluation of economic costs of the two strategies showed that the
      overall cost of the two treatments were comparable when salvage mobilizations
      were taken into account. When in combination with cyclophosphamide or DHAP plus G
      CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally
      treated patients, a significant improvement in mobilization of PBSC with no
      increase in overall cost. 

PMID- 24138498
TI  - An L-DNA G-quadruplex: application for peroxidase DNAzyme.
AB  - L-DNA is the mirror-image form of natural D-DNA. We demonstrate that one left
      handed G-rich sequence can form an L-DNA intramolecular G-quadruplex. Further
      investigation revealed that a DNAzyme formed by an L-nucleotide G-quadruplex
      exhibited peroxidase catalytic efficiency. The enhancement of the color change of
      the oxygenation product ABTS(*-) caused by L-nucleotide G-quadruplex formation
      could be clearly observed with naked eyes. This research provides a new concept
      for the application of the L-DNA peroxidase DNAzyme complex in nuclease
      containing biological systems. 

PMID- 24138499
TI  - mt-tRNA components: synthesis of (2-thio)uridines modified with blocked
      glycine/taurine moieties at C-5,1.
AB  - In this paper, we discuss the usefulness of reductive amination of 5-formyl-2',3'
      O-isopropylidene(-2-thio)uridine with glycine or taurine esters in the presence
      of sodium triacetoxyborohydride (NaBH(OAc)3) for the synthesis of the native
      mitochondrial (mt) tRNA components 5-carboxymethylaminomethyl(-2-thio)uridine
      (cmnm(5)(s(2))U) and 5-taurinomethyl(-2-thio)uridine (taum(5)(s(2))U) with a
      blocked amino acid function. 2-(Trimethylsilyl)ethyl and 2-(p-nitrophenyl)ethyl
      esters of glycine and 2-(2,4,5-trifluorophenyl)ethyl ester of taurine were
      selected as protection of carboxylic and sulfonic acid residues, respectively.
      The first synthesis of 5-formyl-2',3'-O-isopropylidene-2-thiouridine is also
      reported. 

PMID- 24138500
TI  - A novel synthesis of antiviral nucleoside phosphoramidate and thiophosphoramidate
      prodrugs via nucleoside H-phosphonamidates.
AB  - A novel and efficient method for the preparation of antiviral nucleoside 5'-H
      phosphonamidates has been developed. The oxidization of the H-phosphonamidate
      intermediates with iodine and sulfur afforded nucleoside 5'-phosphoramidates and
      5'-thiophosphoramidates in high yields.

PMID- 24138501
TI  - Phase I study protocol for ex-vivo lentiviral gene therapy for the inherited skin
      disease, Netherton Syndrome.
AB  - Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations
      in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a
      serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor).
      Patients with NS have defective keratinization, hair shaft defects, recurrent
      infections, atopy and a predisposition to skin malignancies. Historically, one in
      ten infants has died before their first birthday. Currently there are no proven
      treatments to cure this condition. A SIN-lentiviral vector encoding the codon
      optimized SPINK5 gene under the control of a 572bp element derived from the human
      involucrin promoter (INVO) can confer compartment specific LEKTI expression in NS
      keratinocytes with restoration of normal skin architecture. Here we detail a
      study protocol for a phase I trial for feasibility and safety evaluations of
      autologous epidermal sheets generated from ex-vivo gene corrected keratinocyte
      stem cells, which will be grafted onto patients with mutation proven NS.

PMID- 24138502
TI  - Response to letter to the editor regarding "Assessment of serum S100B and neuron
      specific enolase levels to evaluate the neurotoxic effects of organic solvent
      exposure" in Clinical Toxicology 2013; (doi:10.3109/15563650.2013.820831).

PMID- 24138503
TI  - Human poisoning with prochloraz imidazole fungicide.

PMID- 24138504
TI  - Reliability of the reported ingested dose for predicting the requirement of N
      acetylcysteine in paracetamol overdose patients.

PMID- 24138505
TI  - Assessment of serum S100B and neuron specific enolase levels to evaluate the
      neurotoxic effects of organic solvent exposure.

PMID- 24138506
TI  - Glyphosate toxicity in animals.

PMID- 24138508
TI  - GPAQ-R: development and psychometric properties of a version of the general
      practice assessment questionnaire for use for revalidation by general
      practitioners in the UK.
AB  - BACKGROUND: The General Practice Assessment Questionnaire (GPAQ) has been widely
      used to assess patient experience in general practice in the UK since 2004. In
      2013, new regulations were introduced by the General Medical Council (GMC)
      requiring UK doctors to undertake periodic revalidation, which includes
      assessment of patient experience for individual doctors. We describe the
      development of a new version of GPAQ - GPAQ-R which addresses the GMC's
      requirements for revalidation as well as additional NHS requirements for surveys
      that GPs may need to carry out in their own practices. METHODS: Questionnaires
      were given out by doctors or practice staff after routine consultations in line
      with the guidance given by the General Medical Council for surveys to be used for
      revalidation. Data analysis and practice reports were provided independently.
      RESULTS: Data were analysed for questionnaires from 7258 patients relating to 164
      GPs in 29 general practices. Levels of missing data were generally low (typically
      4.5-6%). The number of returned questionnaires required to achieve reliability of
      0.7 were around 35 for individual doctor communication items and 29 for a
      composite score based on doctor communication items. This suggests that the
      responses to GPAQ-R had similar reliability to the GMC's own questionnaire and we
      recommend 30 completed GPAQ-R questionnaires are sufficient for revalidation
      purposes. However, where an initial screen raises concern, the survey might be
      repeated with 50 completed questionnaires in order to increase reliability.
      CONCLUSIONS: GPAQ-R is a development of a well-established patient experience
      questionnaire used in general practice in the UK since 2004. This new version can
      be recommended for use in order to meet the UK General Medical Council's
      requirements for surveys to be used in revalidation of doctors. It also meets the
      needs of GPs to ask about patient experience relating to aspects of practice care
      that are not specific to individual general practitioners (e.g. receptionists,
      telephone access) which meet other survey requirements of the National Health
      Service in England. Use of GPAQ-R has the potential to reduce the number of
      surveys that GPs need to carry out in their practices to meet the various
      regulatory requirements which they face.

PMID- 24138507
TI  - Genomic diversity and adaptation of Salmonella enterica serovar Typhimurium from
      analysis of six genomes of different phage types.
AB  - BACKGROUND: Salmonella enterica serovar Typhimurium (or simply Typhimurium) is
      the most common serovar in both human infections and farm animals in Australia
      and many other countries. Typhimurium is a broad host range serovar but has also
      evolved into host-adapted variants (i.e. isolated from a particular host such as
      pigeons). Six Typhimurium strains of different phage types (defined by patterns
      of susceptibility to lysis by a set of bacteriophages) were analysed using
      Illumina high-throughput genome sequencing. RESULTS: Variations between strains
      were mainly due to single nucleotide polymorphisms (SNPs) with an average of 611
      SNPs per strain, ranging from 391 SNPs to 922 SNPs. There were seven
      insertions/deletions (indels) involving whole or partial gene deletions, four
      inactivation events due to IS200 insertion and 15 pseudogenes due to early
      termination. Four of these inactivated or deleted genes may be virulence related.
      Nine prophage or prophage remnants were identified in the six strains. Gifsy-1,
      Gifsy-2 and the sopE2 and sspH2 phage remnants were present in all six genomes
      while Fels-1, Fels-2, ST64B, ST104 and CP4-57 were variably present. Four strains
      carried the 90-kb plasmid pSLT which contains several known virulence genes.
      However, two strains were found to lack the plasmid. In addition, one strain had
      a novel plasmid similar to Typhi strain CT18 plasmid pHCM2. CONCLUSION: The
      genome data suggest that variations between strains were mainly due to
      accumulation of SNPs, some of which resulted in gene inactivation. Unique genetic
      elements that were common between host-adapted phage types were not found. This
      study advanced our understanding on the evolution and adaptation of Typhimurium
      at genomic level.

PMID- 24138509
TI  - Intrapulmonary shunts and its implications for assessment in stroke and divers
      with type II decompression illness.

PMID- 24138510
TI  - Combination therapy: the propitious rationale for drug development.
AB  - Therapeutic options for many infections are extremely limited and at crisis
      point. We run the risk of entering a second pre-antibiotic era. There had been no
      miracle drug for the patients infected by resistant microbial pathogens. Most of
      the very few new drugs under development have problems with their toxicity, or
      pharmacokinetics and pharmacodynamics. We are already decades behind in the
      discovery, characterization and development of new antimicrobials. In that
      scenario, we could not imagine surviving without newer and effective
      antimicrobial agents. Bacteria have been the champions of evolution and are still
      evolving continuously, where they pose serious challenges for humans. Along with
      the crisis of evolving resistance, the condition is made worst by the meager drug
      pipeline for new antimicrobials. Despite ongoing efforts only 2 new antibiotics
      (Telavancin in 2009 and Ceftaroline fosamil in 2010) have been approved since
      2009 pipeline status report of Infectious Disease Society of America (IDSA).
      Recent approval of new combination based antiviral drugs such as Stribild
      (combination of four drugs for HIV treatment) and Menhibrix (combination vaccine
      to prevent meningococcal disease and Haemophilus influenzae type b in children)
      proves that combination therapy is still the most promising approach to combat
      the ever evolving pathogens. Combination therapy involves the drug repurposing
      and regrouping of the existing antimicrobial agents to provide a synergistic
      approach for management of infectious diseases. This review article is an effort
      to highlight the challenges in new drug development and potential of combination
      drug therapy to deal with them. 

PMID- 24138511
TI  - Solution-processed hybrid cathode interlayer for inverted organic solar cells.
AB  - A novel hybrid material CdS/2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline
      (CdS.BCP) was prepared from the decomposition of its organic soluble precursor
      complex Cd(S2COEt)2.(BCP) by low-temperature treatment. CdS.BCP, which integrated
      the favorable properties of solvent durability, and high electron mobility of CdS
      as well as the good hole blocking property of BCP, was designed and developed as
      the interface modification material to improve electron collection in bulk
      heterojunction organic solar cells (OSCs). The inverted OSCs with CdS.BCP as
      buffer layer on ITO showed improved efficiency compared with the pure CdS or BCP.
      Devices with CdS.BCP as interlayer exhibited excellent stability, only 14.19%
      decay of power conversion efficiencies (PCEs) was observed (from 7.47% to 6.41%)
      after stored in glovebox for 3264 h (136 days). Our results demonstrate promising
      potentials of hybrid materials as the interface modification layers in OSCs, and
      provide new insights for the development of new interface modification materials
      in the future. 

PMID- 24138512
TI  - Babesia canis vogeli, Ehrlichia canis, and Anaplasma platys infection in a dog.
AB  - A 12-month-old male neutered mixed breed dog was presented with a history of
      diarrhea, lethargy, emaciation, polydypsia, and sniffling. Physical examination
      findings included pale mucous membranes, increased heart and respiratory rates,
      and normal rectal temperature (38 degrees C). Hematologic abnormalities included
      anemia and thrombocytopenia. Biochemical abnormalities included hypoalbuminemia,
      hyperbilirubinemia, and elevated ALP and ALT activities. A SNAP 4Dx test result
      was positive for Ehrlichia canis. Babesia canis vogeli organisms were found in
      the peripheral blood films, while morulae of E canis were not seen. Real-time
      polymerase chain reaction testing confirmed the presence of both B c vogeli and E
      canis organisms, and also was positive for Anaplasma platys infection. The dog
      recovered following treatment with doxycycline and imidocarb dipropionate, with
      normal hematology and biochemical profiles.

PMID- 24138513
TI  - Progression of radial approach to PCI in the USA: from niche procedure to default
      approach.

PMID- 24138514
TI  - Learning while extracting: 'pacing' lessons from the world of lead extraction.

PMID- 24138516
TI  - Cangrelor: a review on pharmacology and clinical trial development.
AB  - Dual antiplatelet therapy with aspirin and an oral ADP P2Y12 receptor antagonist
      is the standard-of-care for the prevention of ischemic events in patients with
      acute coronary syndrome or undergoing percutaneous coronary intervention (PCI).
      However, currently available ADP P2Y12 receptor antagonists have several
      limitations, such as interindividual response variability, drug-drug
      interactions, slow onset/offset and only oral availability. Cangrelor is a
      reversible, potent, intravenous, competitive inhibitor of the ADP P2Y12 receptor
      that rapidly achieves near complete and predictable platelet inhibition. Along
      with reversible binding to the receptor cangrelor also has a very short half-life
      (3-5 min), which in turn results in a rapid offset of action. These properties
      make cangrelor a promising drug for clinical use in patients undergoing PCI or
      patients waiting for major surgery but still require antiplatelet protection.
      This manuscript provides an update of the current status of knowledge on
      cangrelor, focusing on its pharmacologic properties and clinical trial
      development, including the BRIDGE and CHAMPION-PHOENIX trials. 

PMID- 24138517
TI  - Novel anticoagulants for stroke prevention in atrial fibrillation and chronic
      kidney disease.
AB  - Atrial fibrillation (AF) is about three-times more prevalent in patients with
      chronic kidney disease and the prevalence of AF increases with the degree of
      renal impairment. Clinical studies have shown increased risk of stroke, bleeding
      and death in patients with chronic kidney disease and AF. Despite, this increased
      risk, anticoagulation is underutilized due to increased bleeding risk in this
      population. Recently direct thrombin inhibitors and factor Xa inhibitors have
      been shown to be more efficacious in stroke prevention with reduced bleeding than
      warfarin. As the usage of these novel anticoagulants increases it is important to
      understand the data available in regard to these high risk patients. 

PMID- 24138518
TI  - Integrating anatomical and functional imaging for the assessment of coronary
      artery disease.
AB  - Coronary artery disease (CAD) is a leading cause of morbidity and mortality.
      Invasive cardiac angiography with fractional flow reserve measurement allows for
      the anatomical and functional assessment of CAD. Given the invasive nature of
      invasive cardiac angiography and the risks of procedure-related complications,
      research has focused upon noninvasive methods for anatomical and functional
      measures of CAD. As such, there is growing interest in the development of hybrid
      imaging because it may provide incremental diagnostic information over each
      imaging modality alone. We will provide an overview of the evidence to date on
      the anatomical and functional stratification of CAD and current hybrid
      techniques. 

PMID- 24138519
TI  - Novel approaches for prevention of stroke related to transcatheter aortic valve
      implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutical
      option in patients with aortic stenosis. The methodology has evolved rapidly
      throughout the last decade. Nowadays, peri-procedural circulatory support,
      surgical vascular access, general anesthesia and mechanical ventilation are
      mainly reserved for selected patients. However, numerous challenges need to be
      addressed in order to further improved outcome of this distinct cohort: patient
      selection in general, vascular access strategies, long-term valve performance and
      paravalvular leakage. Another key issue is the risk of cerebrovascular events
      related to TAVI. In this article, the authors review the current literature on
      the risk of cerebrovascular events, the underlying mechanisms, the diagnostic
      read-outs of cerebral injury and their prognostic value, and ultimately discuss
      conceivable concepts for prevention of stroke associated with TAVI. 

PMID- 24138520
TI  - Comparative effectiveness of revascularization strategies in stable ischemic
      heart disease: current perspective and literature review.
AB  - Percutaneous coronary intervention (PCI) and coronary artery bypass grafting
      (CABG) are established strategies for coronary revascularization in the setting
      of ischemic heart disease. Multiple randomized controlled trials and
      observational studies have compared the impact of the two modalities on the
      patients' quality of life, mortality and morbidity, as well as the cost
      effectiveness of these modalities in different clinical setting. CABG is the
      preferred strategy for revascularizations in patients with multi-vessel disease,
      especially in those with higher risk secondary to associated diabetes, left
      ventricular dysfunction or more complex lesions. PCI is a reasonable
      revascularization modality in patients with ischemia and single or low-risk multi
      vessel disease and those with unprotected left main with low complexity anatomy.
      Compared with PCI, CABG is associated with less repeat revascularization, better
      quality of life and improved survival in high-risk patients. Although CABG is
      associated with higher cost, it is probably associated with a reasonable cost per
      quality-adjusted life-year gained in many patients. Therefore, CABG will often be
      a cost-effective strategy, especially in patients with high angiographic
      complexity and/or diabetes. 

PMID- 24138521
TI  - Revascularization strategies in patients with Type 2 diabetes mellitus.
AB  - This review aims to describe new developments in coronary revascularization
      strategies for patients with pre-existing Type 2 diabetes mellitus (DM).
      Recommended strategies for revascularization have been an active area of study
      with recent important developments. In patients with Type 2 DM and multivessel
      coronary artery disease (CAD), coronary artery bypass graft (CABG) surgery is the
      preferred method for revascularization. Patients with DM are at increased risk
      for diffuse cardiovascular disease due to the proinflammatory, prothrombotic
      effects of chronic hyperglycemia. In patients undergoing percutaneous coronary
      intervention, drug-eluting stents and more potent antiplatelet agents especially
      in those presenting with acute coronary syndromes should be employed. 

PMID- 24138522
TI  - The role of drug-eluting stents for the treatment of coronary chronic total
      occlusions.
AB  - First generation drug-eluting stents (DES) had a major impact on our capacity to
      percutaneously treat coronary chronic total occlusions by significantly reducing
      the risk for in-stent restenosis compared to bare metal stents. Second generation
      drug-eluting stents further improved our capacity to treat these complex lesions
      by providing improved deliverability and enhanced efficacy and safety. The
      ongoing development of bioabsorbable stents will likely be the next major
      advancement to improve the durability of chronic total occlusion interventions. 

PMID- 24138523
TI  - Long-term safety of drug-eluting stents.
AB  - Stent implantation in coronary stenosis has revolutionized the treatment of
      coronary artery disease. The introduction of antirestenotic drug coatings further
      improved their efficacy in reducing target vessel revascularizations. With
      increasing use of drug-eluting stents (DES), stent thrombosis (ST) rose as
      potentially fatal major complication. Initially, the incidence of ST late after
      stent implantation seemed to be similar for DES and bare metal stents until
      several studies proved otherwise in first-generation DES. Since then, the design
      and components of DES have been changed and new polymers, drugs and different
      combinations of platelet inhibitors have been introduced to further improve the
      safety of DES. In this review, the authors focus on the relationship between DES,
      lesion anatomy, implantation technique and pharmacology to avoid the occurrence
      of ST. Furthermore, the relationship between dual antiplatelet therapy, bleeding
      rate and its significant impact on patient outcome is discussed. Finally, some
      promising future concepts are highlighted. 

PMID- 24138524
TI  - Drug-coated balloons in interventional cardiology.
AB  - Over the last few years, drug-coated balloon (DCB) therapy has emerged as a
      promising therapeutic intervention for the management of obstructive
      cardiovascular disease. The dictum of this novel technology is that effective
      prevention of restenosis can be achieved by the short-term transfer of
      antiproliferative drug to local arterial tissue by means of a single prolonged
      balloon angioplasty dilatation. Its main attraction is that no foreign body is
      implanted eliminating thus the risk of late inflammatory response to device
      components without preventing positive remodeling. Here, we discuss the evidence
      regarding the effectiveness of DCB in different lesion types and clinical
      settings as well as the types of DCB commercially available or under development.

PMID- 24138525
TI  - Current and new-generation transcatheter aortic valve devices: an update on
      emerging technologies.
AB  - Transcatheter aortic valve implantation (TAVI) has become an accepted treatment
      option for patients with symptomatic severe aortic stenosis who are at high risk
      for traditional surgical aortic valve replacement. In particular, TAVI has been
      shown to reduce mortality in a randomized comparison with medical treatment and
      to be non-inferior to surgical aortic valve replacement in 'high-risk operable'
      patients. From its early stages it became apparent that TAVI has tremendous
      potential and thus considerable efforts were made to design new devices and
      advance valve technology in order to improve outcomes and increase TAVI
      applications in complex anatomies and in patients with multiple co-morbidities.
      In this review, we present the advances in transcatheter aortic valve technology
      and discuss the current evidence on the new-generation TAVI devices. 

PMID- 24138526
TI  - Looking into the future with bioresorbable vascular scaffolds.
AB  - Bioresorbable scaffold technology has evolved over the last few years with a
      number of devices either available or under clinical and preclinical
      investigation. The absence of a permanent metallic segment in the treated vessel
      wall has the potential to address some of the issues still encountered with
      metallic drug-eluting stents despite improvements in stent platform, polymer and
      drug elution. Here, the authors review currently available bioresorbable
      scaffolds for coronary artery use, concentrating on both completed and ongoing
      preclinical and clinical studies, evaluating their use. The authors also discuss
      the potential advantages as well as challenges that these novel devices may face
      in routine clinical practice. 

PMID- 24138527
TI  - Adherence to dual antiplatelet therapy: can we do better?
AB  - Management strategies to ensure medication adherence for patients following
      percutaneous coronary intervention have not changed in recent years despite the
      dismal rates of non-compliance with dual antiplatelet therapy. The goal of this
      review is to emphasis the importance of dual antiplatelet therapy in patients
      following percutaneous coronary intervention, discuss the clinical and economic
      ramifications of premature discontinuation and strategies for improvement. 

PMID- 24138529
TI  - Peritoneal dialysis versus hemodialysis in patients with delayed graft function.
AB  - Delayed graft function (DGF) in kidney transplantation affects adverse outcomes.
      It remains unclear whether the post-transplant dialysis modality alters
      perioperative or long-term graft outcomes. We performed a retrospective
      observational quality initiative at two Canadian renal transplant centers, in
      which DGF occurred in the recipient, necessitating one of peritoneal dialysis
      (PD) or hemodialysis (HD). There was no difference in baseline factors between
      patients with post-transplant PD (n = 14) or HD (n = 63). The use of PD was
      associated with an increased risk of wound infection/leakage (PD 5/14 vs. HD
      6/63, p = 0.024), shorter length of hospitalization (13.7 vs. 18.7 d, p = 0.009)
      and time requiring dialysis post-operatively (6.5 vs 11.0 d, p = 0.043). There
      were no differences in readmission to hospital within 6 months (4/14 vs. 23/63, p
      = 0.759), graft loss (0/14 vs. 2/63, p = 1.000) or acute rejection episodes (1/14
      vs. 4/63, p = 1.000) at one yr, and GFR did not differ between the PD or HD
      groups at 30 d (35.7 vs. 33.8 mL/min/m(2), p = 0.731), six months (46.9 vs. 45.5
      mL/min/m(2), p = 0.835) or one yr (46.6 vs. 44.5 mL/min/m(2), p = 0.746). Further
      research is needed to determine which transplant patients are most appropriate to
      undergo PD catheter removal at the time of transplantation.

PMID- 24138530
TI  - Kie Kian Ang, M.D. Ph.D., 1950-2013.

PMID- 24138531
TI  - Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed
      by human CYP4F2 and CYP4F11.
AB  - Vitamin K plays an essential role in many biological processes including blood
      clotting, maintenance of bone health, and inhibition of arterial calcification. A
      menaquinone form of vitamin K, MK4, is increasingly recognized for its key roles
      in mitochondrial electron transport, as a ligand for the nuclear receptor SXR,
      which controls the expression of genes involved in transport and metabolism of
      endo- and xenobiotics, and as a pharmacotherapeutic in the treatment of
      osteoporosis. Although cytochrome P450 (CYP) 4F2 activity is recognized as an
      important determinant of phylloquinone (K1) metabolism, the enzymes involved in
      menaquinone catabolism have not been studied previously. CYP4F2 and CYP4F11 were
      expressed and purified and found to be equally efficient as in vitro catalysts of
      MK4 omega-hydroxylation. CYP4F2, but not CYP4F11, catalyzed sequential metabolism
      of MK4 to the omega-acid without apparent release of the intermediate aldehyde.
      The omega-alcohol could also be metabolized to the acid by microsomal NAD(+)
      dependent alcohol and aldehyde dehydrogenases. LC-MS/MS analysis of trypsinized
      human liver microsomes (using a surrogate peptide approach) revealed the mean
      concentrations of CYP4F2 and CYP4F11 to be 14.3 and 8.4 pmol/mg protein,
      respectively. Microsomal MK4 omega-hydroxylation activities correlated with the
      CYP4F2 V433M genotype but not the CYP4F11 D446N genotype. Collectively, these
      data expand the lexicon of vitamin K omega-hydroxylases to include the 'orphan'
      P450 CYP4F11 and identify a common variant, CYP4F2 (rs2108622), as a major
      pharmacogenetic variable influencing MK4 catabolism. 

PMID- 24138532
TI  - Asymmetric electrostatic and hydrophobic-hydrophilic interaction forces between
      mica surfaces and silicone polymer thin films.
AB  - We have synthesized model hydrophobic silicone thin films on gold surfaces by a
      two-step covalent grafting procedure. An amino-functionalized gold surface reacts
      with monoepoxy-terminated polydimethylsiloxane (PDMS) via a click reaction,
      resulting in a covalently attached nanoscale thin film of PDMS, and the click
      chemistry synthesis route provides great selectivity, reproducibility, and
      stability in the resulting model hydrophobic silicone thin films. The asymmetric
      interaction forces between the PDMS thin films and mica surfaces were measured
      with the surface forces apparatus in aqueous sodium chloride solutions. At an
      acidic pH of 3, attractive interactions are measured, resulting in instabilities
      during both approach (jump-in) and separation (jump-out from adhesive contact).
      Quantitative analysis of the results indicates that the Derjaguin-Landau-Verwey
      Overbeek theory alone, i.e., the combination of electrostatic repulsion and van
      der Waals attraction, cannot fully describe the measured forces and that the
      additional measured adhesion is likely due to hydrophobic interactions. The
      surface interactions are highly pH-dependent, and a basic pH of 10 results in
      fully repulsive interactions at all distances, due to repulsive electrostatic and
      steric-hydration interactions, indicating that the PDMS is negatively charged at
      high pH. We describe an interaction potential with a parameter, known as the
      Hydra parameter, that can account for the extra attraction (low pH) due to
      hydrophobicity as well as the extra repulsion (high pH) due to hydrophilic
      (steric-hydration) interactions. The interaction potential is general and
      provides a quantitative measure of interfacial hydrophobicity/hydrophilicity for
      any set of interacting surfaces in aqueous solution. 

PMID- 24138533
TI  - Characterization of microsomal prostaglandin E synthase 1 inhibitors.
AB  - Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible terminal synthase
      in PGE2 biosynthesis by inflammatory and cancer cells. Clinical and experimental
      data emphasize that mPGES-1 might be a valuable target, with improved selectivity
      and safety compared to traditional NSAIDs or selective COX-2 inhibitors, in the
      treatment of inflammatory diseases, different types of cancer as well as central
      symptoms elicited by peripheral inflammation. Since the first characterization of
      mPGES-1, the numbers of publications on mPGES-1 structure, pathogenic role and
      inhibitor development have increased exponentially; however, there are currently
      no selective mPGES-1 inhibitors available for clinical use. In this MiniReview,
      we focus on recent advances in the development of selective inhibitors of mPGES-1
      activity, with the aim to discuss the effects of targeting mPGES-1 in different
      inflammatory models in vitro and in vivo. 

PMID- 24138534
TI  - Interactive effects of environmental change and management strategies on regional
      forest carbon emissions.
AB  - Climate mitigation activities in forests need to be quantified in terms of the
      long-term effects on forest carbon stocks, accumulation, and emissions. The
      impacts of future environmental change and bioenergy harvests on regional forest
      carbon storage have not been quantified. We conducted a comprehensive modeling
      study and life-cycle assessment of the impacts of projected changes in climate,
      CO2 concentration, and N deposition, and region-wide forest management policies
      on regional forest carbon fluxes. By 2100, if current management strategies
      continue, then the warming and CO2 fertilization effect in the given projections
      result in a 32-68% increase in net carbon uptake, overshadowing increased carbon
      emissions from projected increases in fire activity and other forest disturbance
      factors. To test the response to new harvesting strategies, repeated thinnings
      were applied in areas susceptible to fire to reduce mortality, and two clear-cut
      rotations were applied in productive forests to provide biomass for wood products
      and bioenergy. The management strategies examined here lead to long-term
      increased carbon emissions over current harvesting practices, although semiarid
      regions contribute little to the increase. The harvest rates were unsustainable.
      This comprehensive approach could serve as a foundation for regional place-based
      assessments of management effects on future carbon sequestration by forests in
      other locations. 

PMID- 24138535
TI  - Catalytic methyl transfer from dimethylcarbonate to carboxylic acids.
AB  - Although methylation reactions are commonplace, currently used reagents are
      hazardous, toxic, and/or unstable. Dimethylcarbonate has been put forth as an
      inexpensive, nontoxic, and "green" potential methylating reagent. Herein we
      report a general, base-catalyzed methyl transfer from dimethylcarbonate to
      carboxylic acids. High selectivity for esterification is observed even in the
      presence of unprotected phenols, and the mild reaction conditions enable
      conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling
      studies suggest a mechanism proceeding by direct methyl transfer from
      dimethylcarbonate to the substrate. 

PMID- 24138536
TI  - A multicenter, prospective, randomized, double-blind study to evaluate the safety
      and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes
      mellitus patients having hypertriglyceridemia not controlled with atorvastatin
      therapy (PRESS VI).
AB  - BACKGROUND: Dyslipidemia due to diabetes is characterized by hypertriglyceridemia
      and reduced levels of high-density lipoprotein cholesterol (HDL-C) and elevated
      or normal levels of low-density lipoprotein cholesterol (LDL-C) in type 2
      diabetes mellitus (T2DM). The objectives of this Phase III study were to evaluate
      the safety, tolerability, and efficacy of saroglitazar (ZYH1) 2-mg and 4-mg
      tablets (LipaglynTM; Zydus Cadila, Ahmedabad, India) compared with placebo in
      patients with diabetic dyslipidemia who are not controlled with atorvastatin 10
      mg therapy. SUBJECTS AND METHODS: This was a 16-week prospective, multicenter,
      randomized, double-blind, placebo controlled, three-arm Phase III study in
      subjects with hypertriglyceridemia (>200 and <500 mg/dL) with T2DM not controlled
      with atorvastatin 10 mg. The study consisted of a run-in period of 4 weeks of
      life-style modification followed by 12 weeks of treatment with saroglitazar (2-mg
      or 4-mg) or placebo tablets. The primary end point was the change in plasma
      triglyceride level compared with baseline and the placebo arm at the end of Week
      12. The secondary exploratory end points were change in lipid profile and fasting
      plasma glucose at Week 12. In total, 302 subjects were randomized to receive one
      of the treatments, saroglitazar 2 mg (n=101) or saroglitazar 4 mg (n=99), or
      matching placebo (n=102). Patients who received study medication and had
      undergone at least one post baseline efficacy evaluation were included in the
      efficacy analysis. RESULTS: At Week 12, saroglitazar 2-mg and 4-mg tablets
      significantly reduced mean plasma triglyceride levels by -45.5+/-3.03% and 
      46.7+/-3.02% (mean+/-SE), respectively, and the difference was significant
      (P<0.001) compared with placebo. Saroglitazar 2 mg demonstrated significant
      decrease in levels of non-HDL-C, very LDL-C, total cholesterol, and fasting
      plasma glucose. Additionally, saroglitazar 4 mg also significantly reduced LDL-C
      and apolipoprotein B levels. Saroglitazar was found to be safe and well tolerated
      by patients. CONCLUSIONS: Saroglitazar appeared to be an effective and safe
      therapeutic option for improving hypertriglyceridemia in patients with T2DM.

PMID- 24138537
TI  - A randomized controlled trial to assess safety, tolerability, and antepartum
      viral load with increased lopinavir/ritonavir dosage in pregnancy.
AB  - HIV mother-to-child transmission (MTCT) is significantly reduced if antepartum
      viral load (apVL) is<50 copies/mL. Pharmacokinetic studies suggest increasing the
      dosage of lopinavir/ritonavir (LPV/r) in pregnancy. It is important to assess
      tolerance, safety, and rate of patients presenting a apVL<50 copies/mL when
      treating with increased dose of LPV/r during pregnancy. Confirmed HIV-infected
      pregnant women with a fetus at a gestational age of 14-33 weeks were randomly
      assigned to receive LPV/r 400/100 or 600/150 mg b.i.d. plus two nucleoside
      analogues (NRTIs). Treatment was discontinued in the case of alanine transaminase
      (ALT) of grade III elevation or higher, glucose, or triglycerides. Thirty-two
      women were randomized to the LPV/r 400/100 mg dose, and 31 women were randomized
      to the 600/150 mg dose. Overall, 9.4% of the women receiving the conventional
      dose, and 17.2% receiving the increased dose, discontinued treatment because of
      adverse events (p=0.29). The rates of gastrointestinal (GI) symptoms, laboratory
      abnormalities, preterm delivery, and low birth weight were similar in both
      groups. There were no cases of HIV MTCT. Among the women with a baseline VL>50
      copies/mL assigned to the conventional dose group, 45% (95% confidence interval
      [CI] 62.5-27.5%) had a apVL>50 copies/mL compared with 10.5% (95% CI 21.6-0.6%)
      of those assigned to the increased dose group (p=0.01). There was no significant
      difference found for the patients with a baseline VL<50 copies/mL. In pregnant
      women with a baseline VL>50 copies/mL, it may be warranted to initiate LPV/r
      dosing at 600/150 mg, whereas the conventional dose is sufficient for pregnant
      women with a baseline VL<50 copies/mL.

PMID- 24138538
TI  - Traps and hyper inflammation - new ways that neutrophils promote or hinder
      survival.
AB  - For a long time neutrophil granulocytes were considered simply as terminally
      differentiated cells with a limited life span and pathogen killing by
      phagocytosis and chemical toxicity being the sole mode of action. However, work
      during the last 10 years has started to change this view fundamentally. Modern
      understanding is that neutrophils have an enormous complexity of functions. This
      review discusses very recent findings on how neutrophils can control the spread
      of pathogens and mediate their killing by mechanisms such as formation of DNA
      nets, how they influence tumour growth and adaptive immune responses and how they
      manoeuvre inside the diverse compartments of the body. It will also describe how
      the normally protective functions of neutrophils can have deleterious
      consequences if they occur in an uncontrolled fashion. These exciting novel
      findings are likely to completely and permanently change our view of this central
      leucocyte population. 

PMID- 24138539
TI  - Transcriptomic analysis of triclosan-susceptible and -tolerant Escherichia coli
      O157:H19 in response to triclosan exposure.
AB  - Triclosan is an active agent that is commonly found in biocide formulations which
      are used by the food industry to control microbial contamination. The aim of this
      study was to use microarray analysis to compare gene expression between a
      triclosan-susceptible Escherichia coli O157:H19 isolate (minimum inhibitory
      concentration [MIC] 6.25 MUg/ml) and its in vitro generated triclosan-tolerant
      mutant (MIC >8,000 MUg/ml). Gene expression profiling was performed on the wild
      type and mutant isogenic pairs after 30 min exposure to the parent MIC for
      triclosan and an untreated control. Microarray analysis was carried out using the
      Affymetrix GeneChip E. coli Genome 2.0 Array, and differential expression of
      genes was analyzed using the pumaDE method in Bioconductor R software. Wild-type
      gene expression was found to be significantly different from the triclosan
      tolerant mutant for a large number of genes, even in the absence of triclosan
      exposure. Significant differences were observed in the expression of a number of
      pathway genes involved in metabolism, transport, and chemotaxis. In particular,
      gene expression in the triclosan-tolerant mutant was highly up-regulated for 33
      of 38 genes belonging to the flagellar assembly pathway. The presence of extended
      flagella in the mutant isolate was confirmed visually by transmission electron
      microscopy, although no significant difference was observed in the motility of
      the parent and mutant at low levels of triclosan. Data from this study show that
      at a transcriptomic level, a triclosan-tolerant E. coli O157:H19 mutant is
      significantly different from the wild-type strain in a number of different
      pathways, providing an increased understanding of triclosan tolerance.

PMID- 24138540
TI  - Occurrence of 3-MCPD and glycidyl esters in edible oils in the United States.
AB  - Fatty acid esters of 3-monochloropropanediol (3-MCPD) and glycidol are processing
      contaminants found in a wide range of edible oils. While both 3 MCPD and glycidol
      have toxicological properties that at present has concerns for food safety, the
      published occurrence data are limited. Occurrence information is presented for
      the concentrations of 3-MCPD and glycidyl esters in 116 retail and/or industrial
      edible oils and fats using LC-MS/MS analysis of intact esters. The concentrations
      for bound 3-MCPD ranged from below the limit of quantitation (<LOQ) to 0.09 mg kg
      1 (ppm) in 22 unrefined oils and from 0.005 to 7.2 mg kg-1 (ppm) in 94 refined
      oils. The concentrations for bound glycidol ranged from <LOQ to 0.03 mg kg-1
      (ppm) in unrefined oil samples and from <LOQ to 10.5 mg kg-1 (ppm) in processed
      oil samples. The highest concentrations for both 3-MCPD and glycidol were seen in
      refined palm oil and palm olein samples. Palm olein samples also contained a
      higher percentage of 3-MCPD in mono-ester form than any other type of oil.

PMID- 24138541
TI  - Cheese consumption and prevalence of overweight and obesity in a Basque adult
      population: a cross-sectional study.
AB  - Studies have reported a negative association between dairy product consumption
      and weight status. However, not as much research has focused on cheese;
      therefore, the aim of this study was to study the association between cheese
      intake and overweight and obesity in a representative Basque adult population. A
      food frequency questionnaire (FFQ) was obtained from a random sample of 1081
      adults (530 males and 551 females, 17-96 years old). Cheese consumption data were
      expressed as g/1000 kcal/day. The prevalence of overweight/obesity was higher in
      men (55.1%) than in women (35.4%) (p < 0.001). Participants with low or moderate
      intake of fresh and processed cheese demonstrated a higher prevalence of excess
      weight, compared with those with higher consumption. The confounding variables
      selected in multivariate analysis were: occupational status and age in both
      genders; and place of residence in men. In conclusion, negative associations were
      found between consumption of some types of cheese and overweight and obesity in
      this population.

PMID- 24138542
TI  - Echocardiographic evaluation of external iliac artery Doppler waveform in
      patients with coronary artery disease.
AB  - Visual interpretation of the Doppler waveform in the common femoral or distal
      external iliac artery (EIA) was reported to be useful in screening for proximal
      peripheral artery occlusive disease (PAOD) in patients with lower limb ischemia.
      Commonly patients with coronary artery disease (CAD) referred for
      echocardiography have coexistent arterial pathology. Therefore, we decided to
      study whether echocardiographic evaluation of the distal EIA flow can be useful
      for detection of PAOD in patients with CAD. We studied 150 consecutive patients
      (pts) with CAD referred for echocardiography. At the end of an echocardiographic
      examination, evaluation of the flow in the distal EIA with an echocardiographic
      probe was performed. The Doppler waveform was classified as normal-with early
      diastolic flow reversal or abnormal-without early diastolic flow reversal.
      Echocardiographic findings were compared in a blinded fashion with the results of
      the ankle brachial index measurements (ABI). Based on the ABI <= 0.9, peripheral
      artery disease was diagnosed in 54 pts (36%) and abnormal external iliac Doppler
      waveform was found in 27 pts (18%). Sensitivity of abnormal external iliac
      Doppler waveform in predicting PAOD was 48%, specificity 99%, positive predictive
      value (PPV) 96%, and negative predictive value 77%. Peripheral arterial occlusive
      disease is common in patients with CAD referred for echocardiographic study.
      Echocardiographic assessment of distal EIA Doppler waveform has low sensitivity,
      but high specificity and high PPV in the diagnosis of peripheral arterial
      occlusive disease. 

PMID- 24138543
TI  - Accurate measurement of gene copy number for human alpha-defensin DEFA1A3.
AB  - BACKGROUND: Multi-allelic copy number variants include examples of extensive
      variation between individuals in the copy number of important genes, most notably
      genes involved in immune function. The definition of this variation, and analysis
      of its impact on function, has been hampered by the technical difficulty of large
      scale but accurate typing of genomic copy number. The copy-variable alpha
      defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10
      copies per diploid genome, and presents considerable challenges for accurate high
      throughput typing. RESULTS: In this study, we developed two paralogue ratio tests
      and three allelic ratio measurements that, in combination, provide an accurate
      and scalable method for measurement of DEFA1A3 gene number. We combined
      information from different measurements in a maximum-likelihood framework which
      suggests that most samples can be assigned to an integer copy number with high
      confidence, and applied it to typing 589 unrelated European DNA samples. Typing
      the members of three-generation pedigrees provided further reassurance that
      correct integer copy numbers had been assigned. Our results have allowed us to
      discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy
      number in European samples. CONCLUSIONS: We have developed an accurate and robust
      method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and
      associated SNPs in Genome-Wide Association Study SNP data provides no evidence
      that alpha-defensin copy number is a strong risk factor for phenotypes such as
      Crohn's disease, type I diabetes, HIV progression and multiple sclerosis.

PMID- 24138545
TI  - Controlling the formation of rodlike V2O5 nanocrystals on reduced graphene oxide
      for high-performance supercapacitors.
AB  - Vanadium pentoxide (V2O5) has attracted much attention for energy storage
      application because of its high Faradaic activity and stable crystal structure,
      which make it a promising electrode material for supercapacitors. However, the
      low electronic conductivity and small lithium-ion diffusion coefficient of V2O5
      limit its practical applications. To overcome these limitations, a facile and
      efficient method is here demonstrated for the fabrication of V2O5/reduced
      graphene oxide (rGO) nanocomposites as electrode materials for supercapacitors.
      With this method, the reduction of graphene oxide can be achieved in a cost
      effective and environmentally friendly solvent, without the addition of any other
      toxic reducing agent. Importantly, this solvent can control the formation of the
      uniform rodlike V2O5 nanocrystals on the surface of rGO. Compared to pure V2O5
      microspheres, the V2O5/rGO nanocomposites exhibited a higher specific capacitance
      of 537 F g(-1) at a current density of 1 A g(-1) in neutral aqueous electrolytes,
      a higher energy density of 74.58 Wh kg(-1) at a power density of 500 W kg(-1),
      and better stability even after 1000 charge/discharge cycles. Their excellent
      performances can be attributed to the synergistic effect of rGO and rodlike V2O5
      nanocrystals. Such impressive results may promote new opportunities for these
      electrode materials in high-energy-density storage systems. 

PMID- 24138544
TI  - The protective effect of VSL#3 on intestinal permeability in a rat model of
      alcoholic intestinal injury.
AB  - BACKGROUND: This study aimed to investigate the mechanism of the probiotic VSL#3
      in acute alcoholic intestinal injury, and evaluate the effect of VSL#3,
      glutamine,VSL#3+glutamine and heat-killed VSL#3 therapy in a rat model. METHODS:
      Six- to eight-week-old male wild-type rats were divided into seven groups. To
      establish the acute alcohol liver disease model, rats received three doses of
      corn starch dissolved in PBS/40% alcohol administered intra-gastrically every 12
      hours. Treatment groups received an intra-gastric dose of VSL#3, Glutamine, heat
      killed VSL#3, or VSL#3+Glutamine 30 minutes prior to alcohol administration. The
      placebo group was treated with PBS prior to alcohol administration. TNFalpha and
      endotoxin in plasma was measured by ELISA and Tachypleus Ameboctye Lysate assays,
      and electron microscopy, Western blotting, and reverse transcription polymerase
      chain reaction were used to identify the mechanisms of VSL#3 in the regulation of
      epithelial permeability. RESULTS: First, compared with control group, endotoxin
      and TNFalpha in alcohol group was obviously high. At the same time, in VSL#3
      group,the expression of endotoxin and TNFalpha obviously lower than the alcohol
      group. And the trends of the expression of tight junction proteins in these
      groups were reversed with the change of endotoxin and TNFalpha. Second, compared
      the groups of VSL#3 with glutamine,VSL#3+glutamine and heat-killed VSL#3,we found
      that both VSL#3 and heat-killed VSL#3, glutamine were as effective as
      VSL#3+glutamine in the treatment of acute alcohol liver disease, the expression
      of endotoxin and TNFalpha were lower than the alcohol group, and tight junction
      proteins were higher than the alcohol group whereas the expression of tight
      junction proteins were higher in VSL#3 + glutamine group than either agent alone,
      but have no significant difference. CONCLUSION: We conclude that VSL#3 treatment
      can regulate the ecological balance of the gut microflora, preventing passage of
      endotoxin and other bacterial products from the gut lumen into the portal
      circulation and down-regulating the expression of TNFalpha, which could otherwise
      down-regulate the expression of tight junction proteins and increase epithelial
      permeability.

PMID- 24138547
TI  - Self-assembly of colloidal nanoparticles inside charged droplets during spray
      drying in the fabrication of nanostructured particles.
AB  - Studies on self-assembly of colloidal nanoparticles during formation of
      nanostructured particles by spray-drying methods have attracted a large amount of
      attention. Understanding the self-assembly phenomenon allows the creation of
      creative materials with unique structures that may offer performance improvements
      in a variety of applications. However, current research on the self-assembly of
      colloidal nanoparticles have been conducted only on uncharged droplet systems. In
      this report, we first investigated the self-assembly processes of charged
      colloidal nanoparticles in charged droplets during spray-drying. Silica
      nanoparticles and polystyrene spheres are used as a model system. To induce a
      positive or a negative charge on the droplets, we used an electrospray method.
      Repulsive and attractive interactions between charged colloidal nanoparticles and
      droplet surface are found to control the self-assembly of colloidal nanoparticles
      inside the charged droplet. Interestingly, self-assembly of colloidal
      nanoparticles inside charged droplets under various processing parameters (i.e.,
      droplet charge, droplet diameter, and surface charge, size, and composition of
      colloidal nanoparticles) allows the formation of unique nanostructured particles,
      including porous and hollow particles with control over the internal structure,
      external shape, number of hollow cavities, and shell thickness, in which this
      level of control cannot be achieved using conventional spray-drying method. 

PMID- 24138546
TI  - Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and
      blood lipids in individuals with type 2 diabetes: a randomised, double-blind
      intervention study.
AB  - BACKGROUND: Low adiponectin levels are discussed as risk factor for
      cardiovascular events. This is of special importance in individuals with type 2
      diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The
      present study aimed to investigate the effect of two plant oils rich in
      polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty
      acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals
      treated either with insulin or oral anti-diabetics (OAD). METHODS: Ninety-two
      subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD
      (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention
      study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or
      mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid
      profile, tocopherol, adiponectin levels and parameters regarding glucose and
      lipid metabolism were assessed at baseline, during and after the intervention.
      RESULTS: Compliance was confirmed by significant increases in gamma-tocopherol
      and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins
      participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks
      compared to baseline) was observed, albeit not significantly different from T2DM
      OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by
      the intervention. CONCLUSIONS: The present study provides evidence that a small
      and easy change in dietary behaviour towards better fat quality moderately
      increases adiponectin levels in T2DM-Ins subjects, independently of the
      administered plant oil.

PMID- 24138548
TI  - Use of first-generation HCV protease inhibitors in patients coinfected by HIV and
      HCV genotype 1.
AB  - BACKGROUND: In HCV genotype 1-infected patients with HIV co-infection, tritherapy
      [HCV protease inhibitors (PIs) plus peg-interferon and ribavirin] has been shown
      to have an increased rate of sustained virological response. However, complex
      drug-to-drug interactions and tolerability issues remain a concern. METHODS:
      Under the auspices of four French scientific societies of medicine, a committee
      was charged of establishing guidelines on the use of first-generation HCV PIs in
      these patients. This scientific committee based its work on preliminary results
      from tritherapy clinical trials in co-infected patients and, since data on these
      patients are still scarce, on the statements already made by the French
      Association for the Study of the Liver (AFEF) on the use of tritherapy in HCV
      mono-infected patients, written in May 2011 and updated in 2012. Each AFEF
      guideline concerning HCV monoinfection was examined to determine whether it could
      be used in the context of HIV/HCV coinfection. RESULTS: These guidelines are
      addressed for the treatment of coinfected patients with various profiles,
      including treatment-naive or patients with failure to previous bitherapy and
      mention those patients for whom tritherapy should start or those for whom it
      should be delayed. Preliminary results of triple therapy as well as factors
      associated to virological response are also discussed. Other issues include
      virological monitoring, clinical and virological criteria to stop therapy,
      practical treatment management, treatment adherence and the management of side
      effects and interactions with antiretroviral drugs. These guidelines were
      submitted for critical review to independent experts.

PMID- 24138549
TI  - Looking backwards and steering forward.

PMID- 24138550
TI  - Clonal evolution in CLL patients as detected by FISH versus chromosome banding
      analysis, and its clinical significance.
AB  - The acquisition of new aberrations during the course of chronic lymphocytic
      leukemia (CLL) named clonal evolution (CE) is usually detected by one of the two
      methods: chromosome banding analysis (CBA) and interphase fluorescence in situ
      hybridization (I-FISH). The purpose of this study was to compare the usefulness
      of FISH and CBA for detecting CE and to evaluate its influence on clinical
      outcome. FISH and CBA were performed at two time points: baseline and follow-up.
      Thirty-eight previously untreated patients with CLL were included in this study.
      CBA and I-FISH revealed CE in 15 (39.5%) and 10 (26.3%) patients, respectively.
      High-risk CE was detected in six cases by CBA and in five cases by I-FISH. In
      four cases with CE-dependent 17p abnormalities detected by CBA, metaphase FISH
      was needed for the confirmation of 17p13.1 deletion. Time from first-line to
      second-line treatment (TTST) and overall survival (OS) did not differ between
      patients with and without CE, irrespective of the CE-detecting method used.
      However, shorter OS (P = 0.043) and TTST (P = 0.006) were observed for the
      patients with potentially relevant CE (rCE) detected by CBA, in which acquired
      aberrations were present in at least 20% of undivided cells and/or changed
      baseline karyotype to abnormal or complex and were not resulting from 13q
      deletion. Our results suggest that some, but not all, CE-dependent aberrations
      detected by CBA influence clinical outcome. Moreover, I-FISH, which was aimed at
      detecting aberrations of prognostic significance, was found to be more precise
      than CBA in their detection, especially TP53 deletion. 

PMID- 24138551
TI  - Prenatal exposure of a novel antipsychotic aripiprazole: impact on maternal,
      fetal and postnatal body weight modulation in rats.
AB  - Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are
      associated with body weight gain in adults with prolonged exposure; but reports
      on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and
      ambiguous. This may be attributed to some unknown mechanism of action, the study
      of which is essential to investigate gestational exposure of equivalent
      therapeutic doses of ARI on maternal and fetal weight gain and its longlasting
      impact on postnatal development and growth of offspring in rodent model. 30
      pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of
      ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of
      each group were sacrificed at GD22 and rest dams were allowed to deliver normally
      and pups were reared postnatally up to 10 weeks of age. In ARI treated groups,
      there was no substantial alteration of body weight gain and food intake in
      pregnant subjects while significant reduction was found in fetal and postnatal
      (pre-and post weaning) body weight gain. ARI was found neutral for substantial
      weight gain in pregnant rats but may induce significant weight loss in fetuses,
      creating long-lasting negative impact on offspring growth (in weight) till PND70.
      Therefore, ARI could be a good alternative of second- generation AAPDs for adult
      females but may not be safe for developing fetuses and offspring. 

PMID- 24138552
TI  - Dystonia associated with lamotrigine therapy: a case report and review of the
      literature.
AB  - The association of extrapyramidal side effects (EPS) with the use of conventional
      antipsychotics is well established, however, EPS can occur during treatment with
      anticonvulsant medications as well. We will present the case of a patient who
      developed an acute dystonic reaction during treatment with lamotrigine and again
      during re-challenge with the same agent. We will review common side effects of
      this medication and the previous reports of lamotrigine-associated dystonias. We
      will also discuss a possible underlying mechanism.

PMID- 24138553
TI  - Using a systems-based approach to overcome reductionist strategies in the
      development of diagnostics.
AB  - Systems biology is a recent addition to the necessary but insufficient
      reductionist approach used in biological research. Systems biology is focused on
      understanding living things as a function of their various interactions at
      multiple levels: not simply as a sum of all their individual parts at any one
      level. This integrative approach yields predictive models of the normal state,
      the disease state and therapeutic actions. Although molecular biology has
      collected an enormous amount of information, including the sequencing of the
      entire human genome in the year 2000, few real-world applications have resulted
      from this molecular approach. The pharmaceutical industry's R&D expenditure has
      increased substantially since 2000, but the number of approved therapeutics has
      dropped simultaneously, due in part to over-reliance on reductionist genomic, and
      not systems, approaches. Instead of using reductionist genomics approaches alone,
      genomics should be incorporated into a multi-level systems biology approach to
      develop diagnostics and therapeutics. 

PMID- 24138554
TI  - 'ICU vampirism' - time for judicious blood draws in critically ill patients.

PMID- 24138555
TI  - Impaired postprandial response of the insulin-like growth factor system in
      maintenance haemodialysis.
AB  - OBJECTIVE: Patients on maintenance haemodialysis (HD) have reduced circulating
      free and bioactive insulin-like growth factor I (IGF-I) due to increased IGF
      binding proteins (IGFBPs). This study investigated the postprandial response of
      the IGF system in HD patients compared with matched healthy subjects. DESIGN AND
      PATIENTS: In a crossover study, twelve nondiabetic HD patients were assigned in a
      random order to three 10-h study days: (1) a non-HD day with one meal served at
      baseline (NHDM1), (2) an HD day with one meal served during HD (HDM1) and (3) an
      HD day with two meals served during and after HD, respectively (HDM2). Twelve
      healthy controls conducted session 1. RESULTS: After the baseline meal, insulin
      concentrations changed similarly in HD patients and controls, whereas
      hyperglycaemia was more prolonged in HD patients (P < 0.001). Postprandial IGFBP
      1 showed greater reductions from baseline in controls (-76% [-81; -70%], mean
      [95% confidence intervals], P < 0.001) than in patients on non-HD days (-45% [
      57; -30%], P < 0.001). In the latter group, the response was even more attenuated
      during HD (-22% [-38; -1%] and -24% [-40; -4%], P <= 0.041). After the second
      meal on HDM2 days, IGFBP-1 further decreased (-50% [-61; -37%], P < 0.001),
      whereas IGFBP-1 returned to baseline levels on the other study days.
      Consistently, at the end of the study days, bioactive IGF-I was significantly
      above baseline only on HDM2 days (+22% [+5; +43%], P = 0.012). CONCLUSIONS: HD
      patients were unable to suppress IGFBP-1 to the same extent as healthy controls,
      which may increase the risk of protein-energy wasting in maintenance HD. A second
      meal after HD, however, effectively suppressed IGFBP-1 and increased bioactive
      IGF-I.

PMID- 24138556
TI  - Synthesis of isosteric triterpenoid derivatives and antifungal activity.
AB  - Dermatomycoses are among the most widespread and common superficial and cutaneous
      fungal infections in humans. There is an urgent need to develop efficient and non
      toxic antimycotic agents with a specific spectrum of activity. Triterpenes have
      been demonstrated to exhibit a wide range of biological activities, including
      antifungal activities. In this study, through hemisynthesis, we aimed to obtain
      triterpene-isosteric molecules from betulinic and ursolic acids to improve the
      antifungal activity and spectrum of action of these compounds. Six compounds were
      resynthesized and tested against eleven mucocutaneous and cutaneous mycotic
      agents. The results of the susceptibility assays were expressed as the minimal
      inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of
      ursolic and betulinic acids that were active against pathogenic yeasts were in
      the range of 16-32 MUg/mL and 4-16 MUg/mL, respectively, whereas fungicidal
      effects were observed at concentrations ranging from 16 to 128 MUg/mL and 8 to
      128 MUg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited
      an antifungal profile similar to that of terbinafine and was the most effective
      derivative against dermatophytes. This strategy led to a promising candidate for
      the development of a new antifungal agent. 

PMID- 24138557
TI  - Two rare-class tricyclic diterpenes with antitubercular activity from the
      Caribbean sponge Svenzea flava. Application of vibrational circular dichroism
      spectroscopy for determining absolute configuration.
AB  - Two new natural products, 3 and 4, and their predecessor 7
      isocyanoisoneoamphilecta-1(14),15-diene (2), of the rare isoneoamphilectane class
      of marine diterpenes, along with the known amphilectane diterpenes 6-8, were
      isolated from the n-hexane extract of the marine sponge Svenzea flava collected
      at Great Inagua Island, Bahamas. The molecular structures of compounds 3 and 4
      were established by spectroscopic (1D/2D NMR, IR, UV, HRMS) methods and confirmed
      by a series of chemical correlation studies. In a first ever case study of the
      assignment of the absolute configuration of a molecule based on the
      isoneoamphilectane carbon skeleton, the absolute configuration of compound 5 was
      established as 3S,4R,7S,8S,11R,12S,13R by application of vibrational circular
      dichroism (VCD). In vitro anti-TB screenings revealed that metabolites 2-4 and,
      in particular, semisynthetic analogue 5, are strong growth inhibitors of
      Mycobacterium tuberculosis H37Rv. 

PMID- 24138558
TI  - Unintended consequences and artifacts.

PMID- 24138559
TI  - Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials.
AB  - Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate
      pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed
      or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013).
      Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging
      innovative treatment approach, which aims at stimulating the body's own immune
      system against HGG by using autologous dendritic cells pulsed with autologous
      tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy
      for HGG in children, bringing additional knowledge and experience to the
      scientific community. However, at the same time, this and other manuscripts urge
      for the next step in treatment development. 

PMID- 24138561
TI  - Influence of amine structural characteristics on N-nitrosamine formation
      potential relevant to postcombustion CO2 capture systems.
AB  - Concerns have arisen for the possible contamination of air or drinking water
      supplies downwind of amine-based CO2 capture facilities by potentially
      carcinogenic N-nitrosamines formed from reactions between flue gas NOx and amine
      solvents. This study evaluated the influence of amine structure on the potential
      to form total N-nitrosamines within the absorber and washwater units of a
      laboratory-scale CO2 capture reactor, and in the solvent after a pressure-cooker
      treatment as a mimic of desorber conditions. Among 16 amines representing 3 amine
      classes (alkanolamines, straight-chain and cyclic diamines, and amino acids), the
      order of the amine was the primary determinant of total N-nitrosamine formation
      in the absorber unit, with total N-nitrosamine formation in the order: secondary
      amines ~ tertiary amines ? primary amines. Similar results were observed upon
      pressure-cooker treatment, due to reactions between nitrite and amines at high
      temperature. For secondary and tertiary amines, total N-nitrosamine formation
      under these desorber-like conditions appeared to be more important than in the
      absorber, but for primary amines, significant formation of total N-nitrosamines
      was only observed in the absorber. For diamines and amino acids, total N
      nitrosamine accumulation rates in washwaters were lowest for primary amines. For
      alkanolamines, however, total N-nitrosamine accumulation in the washwater was
      similar regardless of alkanolamine order, due to the combined effects of amine
      reactivity toward nitrosation and amine volatility. While total N-nitrosamine
      accumulation rates in washwaters were generally 1-2 orders of magnitude lower
      than in the absorber, they were comparable to absorber rates for several primary
      amines. Decarboxylation of the amino acid sarcosine resulted in the accumulation
      of significant concentrations of N-nitrosodimethylamine and N-nitrodimethylamine
      in the washwater. 

PMID- 24138560
TI  - Hydrogen sulfide regulates Ca(2+) homeostasis mediated by concomitantly produced
      nitric oxide via a novel synergistic pathway in exocrine pancreas.
AB  - AIM: The present study was designed to explore the effects of hydrogen sulfide
      (H2S) on Ca(2+) homeostasis in rat pancreatic acini. RESULTS: Sodium hydrosulfide
      (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca(2+)
      concentration ([Ca(2+)]i) in a dose-dependent manner. The NaHS-induced [Ca(2+)]i
      elevation persisted with an EC50 of 73.3 MUM in the absence of extracellular
      Ca(2+) but was abolished by thapsigargin, indicating that both Ca(2+) entry and
      Ca(2+) release contributed to the increase. The [Ca(2+)]i increase was markedly
      inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein
      2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that
      nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an
      EC50 of 64.8 MUM, indicating that NO was involved in the H2S effect. The H2S
      induced [Ca(2+)]i increase was inhibited by pretreatment with U73122,
      xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A,
      indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3)
      receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein
      play roles as intermediate components in the H2S-triggered intracellular
      signaling. INNOVATION: To our knowledge, our study is the first one highlighting
      the effect of H2S on intracellular Ca(2+) dynamics in pancreatic acinar cells.
      Moreover, a novel cascade was presumed to function via the synergistic
      interaction between H2S and NO. CONCLUSION: We conclude that H2S affects
      [Ca(2+)]i homeostasis that is mediated by H2S-evoked NO production via an
      endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate
      PKG-Gq-protein-PLC-IP3 pathway to induce Ca(2+) release, and this pathway is
      identical to the one we recently proposed for a sole effect of NO and the two
      gaseous molecules synergistically function to regulate Ca(2+) homeostasis.

PMID- 24138562
TI  - Single crystalline nanostructures of topological crystalline insulator SnTe with
      distinct facets and morphologies.
AB  - Topological crystalline insulators (TCIs) are a new class of topological
      materials that possess unique metallic surface states protected by crystalline
      mirror symmetry. Their topological surface properties are expected to strongly
      depend on the surface orientation. By combining density functional theory (DFT)
      calculations and synthesis experiments, we demonstrate the controlled growth of
      single crystalline nanostructures of the prototypical TCI SnTe with distinct
      facets and morphologies. Our calculations suggest that the excess energy of the
      {111} surfaces can be either higher or lower than that of the {100} surfaces,
      depending on the stoichiometry, while the {110} is always higher than the {100}.
      In our synthesis experiment, we qualitatively controlled the stoichiometry by
      tailoring the growth temperature and obtained two types of single crystalline
      nanowires: smooth nanowires dominated by {100} facets at high temperatures and
      zigzag nanowires composed of both {100} and {111} surfaces at low temperatures.
      Notably, there is no {110} facet in our nanostructures, strongly supporting the
      DFT calculations. Our device fabrication and electrical characterizations suggest
      that both types of nanowires are suitable for transport studies of topological
      surface states. 

PMID- 24138563
TI  - Estimate of dietary exposure to sulphites in child and adult populations in the
      Basque Country.
AB  - Sulphites are widely used as a preservative and antioxidant additive in food. The
      aim of this study was to assess dietary sulphite intake in adults aged 35-65
      years and in children aged 4-18 years living in the Basque Country, northern
      Spain. We determined sulphite concentrations in 909 samples covering 16 food
      types. The maximum permitted levels were exceeded in 17% of samples. Making
      recommended assumptions for non-quantifiable results, estimates of mean lower and
      upper bounds were calculated for sulphite concentrations in each food type. These
      sulphite data were combined with consumption data derived from 8417 adults from
      the European Prospective Investigation in Cancer and Nutrition cohort in
      Gipuzkoa, recruited in 1992-1995 using a diet history method, and 1055 children
      from the Basque Country Nutrition Children Survey, conducted in 2004-2005 using
      two 24-h recall questionnaires to assess diet. The results were compared with the
      acceptable daily intake (ADI) proposed by the Joint Expert Committee on Food
      Additives (JECFA). The mean dietary exposure to sulphites was 0.08 mg kg-1 bw day
      1, only 11% of the ADI in the overall group of children (4-18 years old), but the
      acceptable intake was exceeded by 4% of 4-6 year olds. For the adults (35-65
      years old), the mean dietary exposure was 0.31 mg kg-1 bw day-1, 45% of the ADI,
      but the acceptable intake was exceeded in 14.6% of cases. The major contributing
      foods were minced meat and other meat products for children and wine for adults.

PMID- 24138564
TI  - The presence of at least three alleles of the ADRB3 Trp64Arg (C/T) and UCP1 
      3826A/G polymorphisms is associated with protection to overweight/obesity and
      with higher high-density lipoprotein cholesterol levels in Caucasian-Brazilian
      patients with type 2 diabetes.
AB  - BACKGROUND: We investigated whether the -3826A/G polymorphism (rs1800592) of the
      uncoupling protein 1 gene (UCP1) and the Trp64Arg polymorphism (rs4994) of the
      beta3-adrenergic receptor gene (ADRB3) are associated with type 2 diabetes
      mellitus (T2DM) and features of metabolic syndrome in a Brazilian-Caucasian
      population. METHODS: Both polymorphisms were genotyped in 1015 T2DM patients and
      561 nondiabetic subjects. The combined effect of both polymorphisms on T2DM and
      metabolic syndrome-related parameters was analyzed according to a triallelic
      inheritance pattern, by which at least three minor alleles from two loci are
      necessary for trait manifestation. RESULTS: UCP1 -3826A/G and ADRB3 Trp64Arg
      polymorphisms were not associated with T2DM (P>0.05). Patients carrying the ADRB3
      64Arg allele had higher fasting plasma glucose and high-density lipoprotein
      cholesterol (HDL-C) than patients with the Trp64Trp genotype (P=0.0001 and
      P=0.015, respectively). The 64Arg allele was also associated with protection
      against overweight/obesity (body mass index >= 25 kg/m(2); odds ratio [OR]=0.598;
      P=0.014). Interestingly, prevalence of overweight/obesity was lower among
      carriers of at least three minor alleles of the -3826A/G and ADRB3 Trp64Arg
      polymorphisms than among patients with fewer than three minor alleles (54.5% vs.
      79.1%; OR=0.288; P=0.007, respectively). Subjects with at least three minor
      alleles also had higher HDL-C levels (P=0.018). CONCLUSIONS: UCP1 -3826A/G and
      ADRB3 Trp64Arg polymorphisms may have a combined effect in the modulation of
      overweight/obesity and HDL-C levels in type 2 diabetes mellitus (T2DM) Caucasian
      Brazilian patients.

PMID- 24138565
TI  - Fracture risk assessment in long-term care: a survey of long-term care
      physicians.
AB  - BACKGROUND: The majority of frail elderly who live in long-term care (LTC) are
      not treated for osteoporosis despite their high risk for fragility fractures.
      Clinical Practice Guidelines for the diagnosis and management of osteoporosis
      provide guidance for the management of individuals 50 years and older at risk for
      fractures, however, they cannot benefit LTC residents if physicians perceive
      barriers to their application. Our objectives are to explore current practices to
      fracture risk assessment by LTC physicians and describe barriers to applying the
      recently published Osteoporosis Canada practice guidelines for fracture
      assessment and prevention in LTC. METHODS: A cross-sectional survey was conducted
      with the Ontario Long-Term Care Physicians Association using an online
      questionnaire. The survey included questions that addressed members' attitudes,
      knowledge, and behaviour with respect to fracture risk assessment in LTC. Closed
      ended responses were analyzed using descriptive statistics and thematic framework
      analysis for open-ended responses. RESULTS: We contacted 347 LTC physicians; 25%
      submitted completed surveys (81% men, mean age 60 (Standard Deviation [SD] 11)
      years, average 32 [SD 11] years in practice). Of the surveyed physicians, 87%
      considered prevention of fragility fractures to be important, but a minority
      (34%) reported using validated fracture risk assessment tools, while 33% did not
      use any. Clinical risk factors recommended by the OC guidelines for assessing
      fracture risk considered applicable included; glucocorticoid use (99%), fall
      history (93%), age (92%), and fracture history (91%). Recommended clinical
      measurements considered applicable included: weight (84%), thyroid-stimulating
      hormone (78%) and creatinine (73%) measurements, height (61%), and Get-Up-and-Go
      test (60%). Perceived barriers to assessing fracture risk included difficulty
      acquiring necessary information, lack of access to tests (bone mineral density, x
      rays) or obtaining medical history; resource constraints, and a sentiment that
      assessing fracture risk is futile in this population because of short life
      expectancy and polypharmacy. CONCLUSION: Perceived barriers to fracture risk
      assessment and osteoporosis management in LTC have not changed recently,
      contributing in part to the ongoing care gap in osteoporosis management. Our
      findings highlight the importance to adapt guidelines to be applicable to the LTC
      environment, and to develop partnerships with stakeholders to facilitate their
      use in clinical practice.

PMID- 24138566
TI  - The cooperative binding energetics of CytR and cAMP receptor protein support a
      quantitative model of differential activation and repression of CytR-regulated
      class III Escherichia coli promoters.
AB  - cAMP receptor protein (CRP) and CytR mediate positive and negative control of
      nine genes in Escherichia coli, most of which are involved in nucleoside
      catabolism and recycling. Five promoters share a common architecture in which
      tandem CRP sites flank an intervening CytR operator (CytO). CytR and CRP bind
      cooperatively to these promoters to form a three-protein, DNA-bound complex that
      controls activation and repression, the levels of which vary markedly among the
      promoters. To understand the specific combinatorial control mechanisms that are
      responsible for this outcome, we have used quantitative DNase I footprinting to
      generate individual site isotherms for each site of protein-DNA interaction. The
      intrinsic affinities of each transcription factor for its respective site and the
      specific patterns of cooperativity and competition underlying the molecular
      interactions at each promoter were determined by a global analysis of these
      titration data. Here we present results obtained for nupGP and tsxP2, adding to
      results published previously for deoP2, udpP, and cddP. These data allowed us to
      correlate the reported levels of activation, repression, and induction with the
      ligation states of these five promoters under physiologically relevant
      conditions. A general pattern of transcriptional regulation emerges that allows
      for complex patterns of regulation in this seemingly simple system. 

PMID- 24138568
TI  - Saline contrast echocardiography for the detection of patent foramen ovale in
      hypoxia: a validation study using intracardiac echocardiography.
AB  - Although the "3 beat rule" is widely utiized to discriminate patent foramen ovale
      (PFO)-mediated right-to-left shunt (RTLS) from intrapulmonary RTLS using saline
      contrast transthoracic echocardiography (SCE), SCE diagnostic performance has yet
      to be validated using an invasive intracardiac standard. Percutaneous PFO
      occluder placement was recently shown to ameliorate hypoxia in patients with
      suspected PFO-mediated RTLS. We evaluated the ability of SCE to predict PFO
      presence and size using intracardiac echocardiography (ICE) as a gold standard in
      a hypoxic cohort. Sixty-three hypoxic patients with suspected PFO-mediated RTLS
      who underwent SCE at rest, with Valsalva maneuver, and with cough prior to ICE
      were evaluated retrospectively. PFO RTLS was defined by ICE findings including
      PFO anatomy, RTLS by saline contrast and color Doppler, and probe patency. SCE
      shunt severity and timing of left heart saline target appearance were compared to
      the presence of ICE-defined PFO RTLS. Forty-seven patients (75%) met criteria for
      PFO-mediated RTLS. A 4 beat cutoff for resting SCE provided optimal diagnostic
      performance for detection of PFO-mediated RTLS with a 71% sensitivity, 94%
      specificity, and 97% positive predictive value (PPV). Valsalva and cough
      maneuvers improved sensitivity compared to rest SCE (89% and 80%, respectively).
      Valsalva SCE shunt severity more accurately predicted PFO size than resting SCE.
      In contrast to the widely accepted "3 beat rule," resting SCE for the detection
      of PFO RTLS in a hypoxic population performs optimally using a 4-cycle cutoff
      with both excellent specificity and PPV. 

PMID- 24138567
TI  - Transcription-factor occupancy at HOT regions quantitatively predicts RNA
      polymerase recruitment in five human cell lines.
AB  - BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied
      by many different transcription factors (TFs). HOT regions were initially defined
      in invertebrate model organisms, and we here show that they are a ubiquitous
      feature of the human gene-regulation landscape. RESULTS: We identified HOT
      regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated
      proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase
      II binding sites, but many are not near the promoters of annotated genes. At HOT
      promoters, TF occupancy is strongly predictive of transcription preinitiation
      complex recruitment and moderately predictive of initiating Pol II recruitment,
      but only weakly predictive of elongating Pol II and RNA transcript abundance. TF
      occupancy varies quantitatively within human HOT regions; we used this variation
      to discover novel associations between TFs. The sequence motif associated with
      any given TF's direct DNA binding is somewhat predictive of its empirical
      occupancy, but a great deal of occupancy occurs at sites without the TF's motif,
      implying indirect recruitment by another TF whose motif is present. CONCLUSIONS:
      Mammalian HOT regions are regulatory hubs that integrate the signals from diverse
      regulatory pathways to quantitatively tune the promoter for RNA polymerase II
      recruitment.

PMID- 24138569
TI  - Viscous conductive glue layer in semitransparent polymer-based solar cells
      fabricated by a lamination process.
AB  - Semitransparent polymer-based solar cells were fabricated by using a low-cost,
      vacuum-free lamination process. This process is to deposit a conductive glue
      solution on the transparent Ag film, followed by lamination with the active
      layer. The glue solution and a mixture of poly(3,4-ethylenedioxythiophene):
      poly(styrenesulfonate) (PEDOT:PSS) and d-sorbitol was used. To allow future
      improvements in the conversion efficiency of these cells, we investigated the
      relationship between major factors of the conductive glue layer and photovoltaic
      property. As a result, it was suggested that photovoltaic property had less of a
      relation to conductivity of the conductive glue layer but a strong correlation
      with the contact area within a certain range of the film thickness of the
      conductive glue layer. The optimized cells exhibited 2.22% and 2.41% of power
      conversion efficiencies during front and backside 100 mW cm(-2) AM1.5G
      illumination with reflection paper, respectively. 

PMID- 24138570
TI  - Frequency and risk factors of contrast-induced nephropathy after cardiac
      catheterization in type II diabetic patients: a study among Egyptian patients.
AB  - Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney
      injury (AKI) in hospitalized patients. Diabetes mellitus remains a consistent
      independent predictor of contrast nephropathy. AIM: To determine frequency and
      predictors of contrast-induced nephropathy after cardiac catheterization in type
      II diabetic patients. PATIENTS AND METHODS: The study included 200 type II
      diabetic patients who underwent cardiac catheterization; serial measurement of
      serum creatinine and creatinine clearance (Before contrast exposure and 48 h),
      creatinine clearance was calculated using Cockcroft-Gault formula. Contrast
      induced nephropathy was defined as rise in serum creatinine 48 h after contrast
      exposure of >=0.5 mg/dL or increased >25% compared to base line creatinine.
      RESULTS: incidence of CIN in type II diabetic patients was 21.5%; incidence of
      CIN in diabetic patients with microalbuminuria was 17%, while incidence of CIN in
      patients with macroalbuminuria levels was 26%. There was a statistically
      significant difference between the patients who suffered from CIN post-procedure
      and patients who did not suffer from CIN regarding the ejection fraction and age
      with low ejection fraction and older patients in CIN group. Multiple logistic
      regression analysis for CIN predictors showed that pre-contrast serum creatinine
      to be the strongest predictor for being at risk of contrast-related, followed by
      age, and lastly albumin/creatinine ratio. CONCLUSION: Our findings suggest that
      diabetic patients, despite having a normal baseline creatinine are at an
      increased risk of developing CIN post-coronary angiography, patients at risk of
      CIN are older patients with high pre-contrast serum creatinine and high urine
      albumin/creatinine ratio.

PMID- 24138571
TI  - Why hydraulic tomography works?

PMID- 24138572
TI  - Histological and Histomorphometric Evaluation of Zirconia Dental Implants
      Modified by Femtosecond Laser versus Titanium Implants: An Experimental Study in
      Fox Hound Dogs.
AB  - PURPOSE: This study applied femtosecond laser technology to zirconia dental
      implants (Bredent GmbH & Co.KG, Senden, Germany) to generate a surface texture of
      microgrooves over the entire intraosseous surface, analyzing its behavior in an
      in vivo model in comparison with titanium implants with sandblasted and acid
      etched surfaces. MATERIALS AND METHODS: The study used six American Fox Hound
      dogs. Each received four implants per hemi-mandible, making a total of eight
      implants per animal. The 48 immediate loaded implants were divided into two
      groups of 24 titanium implants (control group) and 24 zirconia implants
      (study/test group), distributed randomly. Bone-to-implant contact (BIC) values
      and crestal resorption were determined at 1 and 3 months, also measuring calcium,
      phosphorous, and carbon concentrations by means of energy dispersive x-ray.
      RESULTS: BIC percentages after 30 days were 51.36% for titanium implants and
      44.68% for zirconia implants. After 90 days, values increased to 61.73% in
      titanium and 47.94% in zirconia implants. After 30 days, there was more crestal
      bone lost in the titanium group (0.77 mm) compared with the zirconia group (0.01
      mm). After 90 days, zirconia implants showed greater marginal bone resorption
      (1.25 mm) compared with the titanium group (0.37 mm). CONCLUSIONS: The present
      study shows that zirconia implants with modified surfaces can produce good
      osseointegration values when compared with titanium implants in terms of BIC and
      crestal bone resorption at 1 and 3 months.

PMID- 24138573
TI  - Cytogenetic risk grouping by the monosomal karyotype classification is superior
      in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem
      cell transplantation in complete remission.
AB  - We retrospectively analyzed the impact of cytogenetic abnormalities grouped
      according to the monosomal karyotype (MK) classification or the Southwest
      Oncology/Eastern Cooperative Oncology Group (SWOG/ECOG) definition in 263
      patients with acute myeloid leukemia (AML) who underwent allogeneic stem cell
      transplantation (alloSCT) in complete remission (CR) at our center. Risk grouping
      using the MK criteria shows a highly significant difference in 5-yr overall
      survival (OS) ranging between 67%, for the most favorable, and 32%, for the
      poorest risk group (P = 0.001). Although similarly precise in predicting OS, the
      MK scheme better separates patients with respect to relapse incidence as compared
      to the SWOG/ECOG grouping (P = 0.0001 vs. P = 0.01). Notably, patients displaying
      non-MK abnormalities (MK-) had a 5-yr relapse incidence identical to those
      cytogenetically normal (CN), that is 24%. Multivariate analysis revealed that the
      MK classification is an independent prognosticator and superior in predicting OS
      (hazard ratios, HR 3.74, P = 0.01) and relapse incidence (HR 3.74, P = 0.005) as
      compared to the SWOG/ECOG criteria. Finally, subgroup analysis revealed that the
      prognostic capacity of the MK classification is highly significant in patients
      treated with standard myeloablative conditioning prior to alloSCT (P = 0.0011 for
      OS, P = 0.0007 for relapse). In contrast, the MK grouping failed to predict OS or
      relapse incidence in patients treated with reduced intensity conditioning. Taken
      together, these results indicate that the MK classification is superior in
      predicting the overall outcome of patients with AML undergoing alloSCT in CR.
      Furthermore, our data suggest that the genetic risk profile of MK- and CN
      patients is mostly overlapping in this setting. 

PMID- 24138575
TI  - A Novel Catalytic Function of Synthetic IgG-Binding Domain (Z Domain) from
      Staphylococcal Protein A: Light Emission with Coelenterazine.
AB  - The synthetic IgG-binding domain (Z domain) of staphylococcal protein A catalyzes
      the oxidation of coelenterazine to emit light like a coelenterazine-utilizing
      luciferase. The Z domain derivatives (ZZ-gCys, Z-gCys and Z-domain) were purified
      and the luminescence properties were characterized by comparing with
      coelenterazine-utilizing luciferases, including Renilla luciferase, Gaussia
      luciferase and the catalytic 19 kDa protein of Oplophorus luciferase. Three Z
      domain derivatives showed luminescence activity with coelenterazine and the order
      of the initial maximum intensity of luminescence was ZZ-gCys (100%) > Z-gCys
      (36.8%) > Z-domain (1.1%) > bovine serum albumin (BSA; 0.9%) > staphylococcal
      protein A (0.1%) and the background value of coelenterazine (0.1%) in our
      conditions. The luminescence properties of ZZ-gCys showed the similarity to that
      of Gaussia luciferase, including the luminescence pattern, the emission spectrum,
      the stimulation by halogen ions and nonionic detergents and the substrate
      specificity for coelenterazine analogues. In contrast, the luminescence
      properties of Z-gCys were close to the catalytic 19 kDa protein of Oplophorus
      luciferase. The catalytic region of the Z domain for the luminescence reaction
      might be different from the IgG-binding region of the Z domain.

PMID- 24138574
TI  - Mass spectrometric protein maps for biomarker discovery and clinical research.
AB  - Among the wide range of proteomic technologies, targeted mass spectrometry (MS)
      has shown great potential for biomarker studies. To extend the degree of
      multiplexing achieved by selected reaction monitoring (SRM), we recently
      developed SWATH MS. SWATH MS is a variant of the emerging class of data
      independent acquisition (DIA) methods and essentially converts the molecules in a
      physical sample into perpetually re-usable digital maps. The thus generated SWATH
      maps are then mined using a targeted data extraction strategy, allowing us to
      profile disease-related proteomes at a high degree of reproducibility. The
      successful application of both SRM and SWATH MS requires the a priori generation
      of reference spectral maps that provide coordinates for quantification. Herein,
      we demonstrate that the application of the mass spectrometric reference maps and
      the acquisition of personalized SWATH maps hold a particular promise for
      accelerating the current process of biomarker discovery. 

PMID- 24138577
TI  - Perfusion computed tomography thresholds defining ischemic penumbra and infarct
      core: studies in a rat stroke model.
AB  - BACKGROUND: Perfusion computed tomography is becoming more widely used as a
      clinical imaging tool to predict potentially salvageable tissue (ischemic
      penumbra) after ischemic stroke and guide reperfusion therapies. AIMS: The study
      aims to determine whether there are important changes in perfusion computed
      tomography thresholds defining ischemic penumbra and infarct core over time
      following stroke. METHODS: Permanent middle cerebral artery occlusion was
      performed in adult outbred Wistar rats (n = 6) and serial perfusion computed
      tomography scans were taken every 30 mins for 2 h. To define infarction
      thresholds at 1 h and 2 h post-stroke, separate groups of rats underwent 1 h (n =
      6) and 2 h (n = 6) of middle cerebral artery occlusion followed by reperfusion.
      Infarct volumes were defined by histology at 24 h. Co-registration with perfusion
      computed tomography maps (cerebral blood flow, cerebral blood volume, and mean
      transit time) permitted pixel-based analysis of thresholds defining infarction,
      using receiver operating characteristic curves. RESULTS: Relative cerebral blood
      flow was the perfusion computed tomography parameter that most accurately
      predicted penumbra (area under the curve = 0.698) and also infarct core (area
      under the curve = 0.750). A relative cerebral blood flow threshold of < 75% of
      mean contralateral cerebral blood flow most accurately predicted penumbral tissue
      at 0.5 h (area under the curve = 0.660), 1 h (area under the curve = 0.659), 1.5
      h (area under the curve = 0.636), and 2 h (area under the curve = 0.664) after
      stroke onset. A relative cerebral blood flow threshold of < 55% of mean
      contralateral most accurately predicted infarct core at 1 h (area under the curve
      = 0.765) and at 2 h (area under the curve = 0.689) after middle cerebral artery
      occlusion. CONCLUSIONS: The data provide perfusion computed tomography defined
      relative cerebral blood flow thresholds for infarct core and ischemic penumbra
      within the first two hours after experimental stroke in rats. These thresholds
      were shown to be stable to define the volume of infarct core and penumbra within
      this time window.

PMID- 24138578
TI  - Ethynyl side chain hydration during synthesis and workup of "clickable"
      oligonucleotides: bypassing acetyl group formation by triisopropylsilyl
      protection.
AB  - Clickable oligonucleotides with ethynyl residues in the 5-position of pyrimidines
      ((eth)dC and (eth)dU) or the 7-position of 7-deazaguanine ((eth)c(7)G(d)) are
      hydrated during solid-phase oligonucleotide synthesis and workup conditions. The
      side products were identified as acetyl derivatives by MALDI-TOF mass spectra of
      oligonucleotides and by detection of modified nucleosides after enzymatic
      phosphodiester hydrolysis. Ethynyl -> acetyl group conversion was also studied on
      ethynylated nucleosides under acidic and basic conditions. It could be shown that
      side chain conversion depends on the nucleobase structure. Triisopropylsilyl
      residues were introduced to protect ethynyl residues from hydration. Pure, acetyl
      group free oligonucleotides were isolated after desilylation in all cases.

PMID- 24138576
TI  - Next-generation sequencing for mitochondrial disorders.
AB  - A great deal of our understanding of mitochondrial function has come from studies
      of inherited mitochondrial diseases, but still majority of the patients lack
      molecular diagnosis. Furthermore, effective treatments for mitochondrial
      disorders do not exist. Development of therapies has been complicated by the fact
      that the diseases are extremely heterogeneous, and collecting large enough
      cohorts of similarly affected individuals to assess new therapies properly has
      been difficult. Next-generation sequencing technologies have in the last few
      years been shown to be an effective method for the genetic diagnosis of inherited
      mitochondrial diseases. Here we review the strategies and findings from studies
      applying next-generation sequencing methods for the genetic diagnosis of
      mitochondrial disorders. Detailed knowledge of molecular causes also enables
      collection of homogenous cohorts of patients for therapy trials, and therefore
      boosts development of intervention.

PMID- 24138579
TI  - Inclusion body myositis: from immunopathology and degenerative mechanisms to
      treatment perspectives.
AB  - Inclusion body myositis is the most common inflammatory myopathy above the age of
      50. It becomes clinically apparent around the fourth decade and leads to a
      slowly, but relentlessly progressive decline in muscular wasting and weakness.
      The pathology consists of a complex network of inflammatory and degenerative
      mechanisms, which lead to an attack of muscle fibers by auto-reactive T cells and
      possibly antibodies. At the same time, various aberrant proteins accumulate
      within the muscle fibers, including beta-amyloid, tau and alpha-synuclein.
      Several key components of proinflammatory cell stress mechanisms such as nitric
      oxide production and macroautophagic processing contribute to the muscle fiber
      damage. So far, none of the anti-inflammatory or immunomodulatory treatment
      efforts have been able to halt the disease progression and help the patients. In
      this summary, the current concept of the complex disease pathology of IBM is
      reviewed with a focus on recent findings as well as future treatment
      perspectives. 

PMID- 24138580
TI  - Management of mother's own milk for very preterm infants in tertiary-level
      neonatal units in the Ile-de-France region in France.

PMID- 24138581
TI  - Oxidation of dissolved elemental mercury by thiol compounds under anoxic
      conditions.
AB  - Mercuric ion, Hg(2+), forms strong complexes with thiolate compounds that
      commonly dominate Hg(II) speciation in natural freshwater. However, reactions
      between dissolved aqueous elemental mercury (Hg(0)aq) and organic ligands in
      general, and thiol compounds in particular, are not well studied although these
      reactions likely affect Hg speciation and cycling in the environment. In this
      study, we compared the reaction rates between Hg(0)aq and a number of selected
      organic ligands with varying molecular structures and sulfur (S) oxidation states
      in dark, anoxic conditions to assess the role of these ligands in Hg(0)aq
      oxidation. Significant Hg(0)aq oxidation was observed with all thiols but not
      with ligands containing no S. Compounds with oxidized S (e.g., disulfide)
      exhibited little or no reactivity toward Hg(0)aq either at pH 7. The rate and
      extent of Hg(0)aq oxidation varied greatly depending on the chemical and
      structural properties of thiols, thiol/Hg ratios, and the presence or absence of
      electron acceptors. Smaller aliphatic thiols and higher thiol/Hg ratios resulted
      in higher Hg(0)aq oxidation rates than larger aromatic thiols at lower thiol/Hg
      ratios. The addition of electron acceptors (e.g., humic acid) also led to
      substantially increased Hg(0)aq oxidation. Our results suggest that thiol-induced
      oxidation of Hg(0)aq is important under anoxic conditions and can affect Hg redox
      transformation and bioavailability for microbial methylation. 

PMID- 24138582
TI  - Field-effect modulation of thermoelectric properties in multigated silicon
      nanowires.
AB  - Electric-field-induced charge carriers typically exhibit greater mobility over
      carriers contributed by chemical dopants and offer a powerful mechanism for
      thermoelectric power factor enhancement. We fabricate multigated silicon
      nanowires (Si NWs) and demonstrate significant modulation of electrical
      conductivity and the Seebeck coefficient with gate bias. Because of the higher
      mobility of field-effect charge carriers, we demonstrate that power factor for
      the gated Si NWs is similar to the highest values reported for n-type Si
      nanostructures despite charge transport only occurring at the NW surface. Field
      effect doping is a promising strategy for optimizing power factor and may result
      in significant power factor enhancement in smaller diameter Si NWs where high
      average carrier densities can be obtained with induced surface charge. 

PMID- 24138583
TI  - New paradigm for allosteric regulation of Escherichia coli aspartate
      transcarbamoylase.
AB  - For nearly 60 years, the ATP activation and the CTP inhibition of Escherichia
      coli aspartate transcarbamoylase (ATCase) has been the textbook example of
      allosteric regulation. We present kinetic data and five X-ray structures
      determined in the absence and presence of a Mg(2+) concentration within the
      physiological range. In the presence of 2 mM divalent cations (Mg(2+), Ca(2+),
      Zn(2+)), CTP does not significantly inhibit the enzyme, while the allosteric
      activation by ATP is enhanced. The data suggest that the actual allosteric
      inhibitor of ATCase in vivo is the combination of CTP, UTP, and a divalent
      cation, and the actual allosteric activator is a divalent cation with ATP or ATP
      and GTP. The structural data reveals that two NTPs can bind to each allosteric
      site with a divalent cation acting as a bridge between the triphosphates. Thus,
      the regulation of ATCase is far more complex than previously believed and calls
      many previous studies into question. The X-ray structures reveal that the
      catalytic chains undergo essentially no alternations; however, several regions of
      the regulatory chains undergo significant structural changes. Most significant is
      that the N-terminal region of the regulatory chains exists in different
      conformations in the allosterically activated and inhibited forms of the enzyme.
      Here, a new model of allosteric regulation is proposed. 

PMID- 24138585
TI  - High performance and stable N-channel organic field-effect transistors by
      patterned solvent-vapor annealing.
AB  - We report the fabrication of high-performance, printed, n-channel organic field
      effect transistors (OFETs) based on an N,N-dialkyl-substituted-(1,7&1,6)
      dicyanoperylene-3,4:9,10-bis(dicarboximide) derivative, PDI-RCN2, optimized by
      the solvent-vapor annealing (SVA) process. We performed a systematic study on the
      influence of solubility and the chemical structure of a solvent used for the SVA
      process on the ordering and orientation of PDI-RCN2 molecules in the thin film.
      The PDI-RCN2 film showed improved crystallinity under vapor annealing with the
      aliphatic 1,2-dichloroethane (DCE) as a marginal solvent. The n-type OFETs with
      DCE-vapor-annealed PDI-RCN2 show highly improved charge-carrier mobility of ~0.5
      cm(2) V(-1) s(-1) and higher stability under gate bias stress than the pristine
      OFETs. This large performance improvement was mainly attributed to increased
      crystallinity of the semiconductor thin film, enhancing pi-pi stacking. We also
      introduced a new method to pattern crystallinity of a certain region in the
      semiconducting film by selective exposure to the solvent vapor using a shadow
      mask. The crystal-patterned PDI-RCN2 OFETs exhibit decreased off-currents by ~10*
      and improved gate bias stability by minimizing crosstalk, reducing leakage
      current between devices, and reducing the density of charge trap states of the
      organic semiconductor.

PMID- 24138584
TI  - Expression of mucoid induction factor MucE is dependent upon the alternate sigma
      factor AlgU in Pseudomonas aeruginosa.
AB  - BACKGROUND: Alginate overproduction in P. aeruginosa, also referred to as
      mucoidy, is a poor prognostic marker for patients with cystic fibrosis (CF). We
      previously reported the construction of a unique mucoid strain which
      overexpresses a small envelope protein MucE leading to activation of the protease
      AlgW. AlgW then degrades the anti-sigma factor MucA thus releasing the
      alternative sigma factor AlgU/T (sigma(22)) to initiate transcription of the
      alginate biosynthetic operon. RESULTS: In the current study, we mapped the mucE
      transcriptional start site, and determined that P(mucE) activity was dependent on
      AlgU. Additionally, the presence of triclosan and sodium dodecyl sulfate was
      shown to cause an increase in P(mucE) activity. It was observed that mucE
      mediated mucoidy in CF isolates was dependent on both the size of MucA and the
      genotype of algU. We also performed shotgun proteomic analysis with cell lysates
      from the strains PAO1, VE2 (PAO1 with constitutive expression of mucE) and
      VE2DeltaalgU (VE2 with in-frame deletion of algU). As a result, we identified
      nine algU-dependent and two algU-independent proteins that were affected by
      overexpression of MucE. CONCLUSIONS: Our data indicates there is a positive
      feedback regulation between MucE and AlgU. Furthermore, it seems likely that MucE
      may be part of the signal transduction system that senses certain types of cell
      wall stress to P. aeruginosa.

PMID- 24138586
TI  - Optimizing the mobility of residents with dementia: a pilot study promoting
      healthcare aide uptake of a simple mobility innovation in diverse nursing home
      settings.
AB  - BACKGROUND: Almost 90 percent of nursing home residents have some type of
      mobility limitation. Many spend most of their waking hours lying in bed or
      sitting. Such inactivity can negatively affect residents' health and general well
      being. This pilot study aimed to assess (1) the effect of the sit-to-stand
      activity on mobility outcomes of nursing home residents, (2) the effect of an
      audit-and-feedback intervention on uptake of the sit-to-stand activity by
      healthcare aides, and (3) the contextual factors influencing uptake of the sit-to
      stand activity by healthcare aides. METHODS: This quasi-experimental pilot study
      was conducted in two nursing homes in western Canada. Twenty-six residents with
      dementia completed the sit-to-stand activity with 56 healthcare aides during
      daily care; separately, 71 healthcare aides completed a research use and context
      survey. Preliminary mobility feedback was presented to healthcare aides in one
      site. Resident mobility was measured using the 30-second sit-to-stand test.
      Healthcare aide uptake of the activity was measured using documentation
      flowsheets and a survey-based measure. Context was measured using the Alberta
      Context Tool. Mobility and uptake outcomes were analyzed over time and by site
      with analysis of covariance. Spearman and Pearson correlations were used to
      correlate context data with research use. RESULTS: Residents who more frequently
      completed the sit-to-stand activity were more likely to maintain or improve
      mobility compared with those who completed it less frequently (F=4.46; p=0.046,
      after adjustment for age). Uptake for one site was significantly different from
      the other (t-score=2.67; p=0.01, after adjustment for resident covariates). The
      audit-and-feedback intervention was associated with increased uptake of the
      activity from pre-intervention to post-intervention (t-score=-2.48; p=0.02). More
      context domains correlated significantly with aides' use of conceptual research
      and information sources in one site than the other. CONCLUSIONS: The sit-to-stand
      activity is a promising means to maintain or improve transfer ability of nursing
      home residents with dementia. In the nursing home with initially weak uptake,
      strengthened uptake followed an audit-and-feedback intervention. Activity
      participation was higher in the site with stronger correlations between context
      and measured research use. Results are sufficiently promising to warrant
      proceeding with a full clinical trial.

PMID- 24138587
TI  - Effect of mesenteric lymph duct ligation on gene expression profiles of renal
      tissue in hemorrhagic shock rats with fluid resuscitation.
AB  - BACKGROUND: Acute kidney injury (AKI), a common pathological process following
      hemorrhagic shock, can lead to an internal milieu disorder, which is an important
      factor of multiple organ failure (MOF). It has been shown that the mesenteric
      lymph return plays a deleterious effect on MOF induced by hemorrhagic shock. In
      this study, we investigated the effects of mesenteric lymph duct ligation (MLDL)
      on gene expression profiles of renal tissue following hemorrhagic shock with
      fluid resuscitation. METHODS: After establishment of hemorrhagic shock model and
      fluid resuscitation in rats of shock and shock ligation groups, the MLDL was
      performed in shock ligation group, and only threading under the mesenteric lymph
      duct in the shock group. Then, the fixed position renal tissue was taken out for
      homogenate in two groups at 3 h after resuscitation, the total mRNA was
      extracted, reversely transcribed into cDNAs and marked with Cy3 and Cy5. The
      cDNAs were subjected for microarray scanning with 12,028 cDNA probes; the
      differentially expressed genes between two groups were analyzed. RESULTS: In the
      5812 valid dates of rat genomes transcription, there were 34 known differentially
      expressed genes between the two groups, of which 11 genes were up-regulated
      whereas 23 genes were down-regulated by MLDL. These different expressed genes
      encoding protein function were mainly involved in signal transduction,
      transcription regulation, metabolism, transport, cell growth, cell cycle, cell
      adhesion, cell movement, cellular component, and biological process. CONCLUSIONS:
      The mechanism of MLDL alleviating the AKI aftershock might be associated with up-
      or down-regulation of the above gene expressions.

PMID- 24138589
TI  - Medical students should engage themselves more in academic medicine.

PMID- 24138588
TI  - Combined baseline strain dyssynchrony index and its acute reduction predicts mid
      term left ventricular reverse remodeling and long-term outcome after cardiac
      resynchronization therapy.
AB  - The objective of this study was to test the hypothesis that combining assessment
      of baseline radial strain dyssynchrony index (SDI), that expressed both left
      ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute
      changes in this index can yield more accurate prediction of mid-term responders
      and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI
      for 75 CRT patients was calculated as the average difference between peak and end
      systolic speckle tracking strain from 6 segments of the mid-LV short-axis view
      before and 8 +/- 2 days after CRT. Mid-term responder was defined as >= 15%
      decrease in LV end-systolic volume 6 +/- 2 months after CRT. Long-term outcome
      was tracked over 5 years. Baseline radial SDI >= 6.5% is considered predictive of
      responder and favorable outcome, as previously reported. Acute reduction in
      radial SDI >= 1.5% was found to be the best predictor of mid-term responders with
      CRT. Furthermore, patients with acute reductions in radial SDI >=1.5% were
      associated with a significantly more favorable long-term outcome after CRT than
      those with radial SDI <1.5% (log rank P < 0.001). An important findings were that
      baseline radial SDI >=6.5% and acute reductions in radial SDI >= 1.5% in 42
      patients were associated with the highest event-free survival rate of 92%,
      whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with
      low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of
      baseline radial SDI and its acute reduction after CRT may have clinical
      implications for predicting responders and thus patients' care.

PMID- 24138590
TI  - Rapid on-site assessment of specimens by biomedical scientists improves the
      quality of head and neck fine needle aspiration cytology.
AB  - OBJECTIVE: Immediate rapid on-site assessment (ROSA) of fine needle aspiration
      cytology (FNAC) specimens by biomedical scientists (BMS), the UK equivalent of
      cytotechnologists, or by pathologists may improve specimen quality and cellular
      adequacy rates for lymph node, head and neck and thyroid FNAC. The aim of this
      study was to evaluate the effect of introducing ROSA by BMS in an outpatient
      clinic setting. METHODS: The adequacy rate and sensitivity of histological
      diagnosis for lymph node, thyroid and salivary gland FNAC samples were determined
      before and after the introduction of BMS ROSA. The additional financial costs and
      time required to perform this service were also estimated. RESULTS: Thirty-one
      patients underwent ultrasound (US)-guided FNAC with ROSA and 151 without. ROSA
      reduced the number of FNAC insufficient in quality for diagnosis from 43% to 19%
      (P = 0.0194). The estimated additional cost for pathology per patient for ROSA
      was between L52.05 and L70.74, equivalent to ?65.40/US $83.90 and ?88.89/US
      $114.0, respectively, an increase of between 28% and 49% from the original cost.
      ROSA necessitated an additional 6 minutes clinic time per patient, reducing the
      number of patients that could be seen in an average clinic from 13 to 10 as well
      as requiring increased laboratory time for FNAC slide assessment. CONCLUSION:
      ROSA by suitably trained biomedical scientists and with appropriate consultant
      pathologist support can improve the quality of FNAC sampling for head and neck
      lesions. Although ROSA resulted in both additional financial and time costs,
      these are more than likely to be offset by a reduction in patients returning to
      clinic for repeat FNAC or undergoing unnecessary surgery.

PMID- 24138591
TI  - Simultaneous and confirmative detection of multi-residues of beta2-agonists and
      beta-blockers in urine using LC-MS/MS/MS coupled with beta-receptor molecular
      imprinted polymer SPE clean-up.
AB  - A liquid chromatography-linear ion-trap spectrometry (LC-MS3) method using beta
      receptor molecular-imprinted polymer (MIP) solid-phase extraction (SPE) as clean
      up was developed to determine simultaneously and confirmatively residues of 25
      beta2-agonists and 21 beta-blockers in urine samples. Urine samples were
      subjected to enzymatic hydrolysis by beta-glucoronidase/arylsulphatase, and then
      extracted with perchloric acid. Sample clean-up was performed using beta-receptor
      MIP SPE. A Supelco Ascentis(r) express Rp-Amide column was used to separate the
      analytes, and MS3 detection used an electrospray ionisation source in positive
      ion mode. Recovery studies were carried out using blank urine samples fortified
      with the 46 analytes at the levels of 0.5, 1.0 and 2.0 MUg l-1. Recoveries were
      obtained ranging from 60.1% to 109.9% with relative standard deviations (RSDs, n
      = 7) from 0.5% to 19.4%. The limits of detection (LODs) and limits of
      quantitation (LOQs) of the 46 analytes in urine were 0.02-0.18 and 0.05-0.60 MUg
      l-1, respectively. As a result of the selective clean-up by MIP SPE and MS3
      detection of the target drugs, the sensitivity and accuracy of the present method
      was high enough for monitoring beta2-agonist and beta-blocker residues in urine
      samples. Satisfactory results were obtained in the process of the determination
      of positive urine samples.

PMID- 24138592
TI  - Loss of gastric gland mucin-specific O-glycan is associated with progression of
      differentiated-type adenocarcinoma of the stomach.
AB  - Gastric gland mucin secreted from the lower portion of the gastric mucosa
      contains unique O-linked oligosaccharides having terminal alpha1,4-linked N
      acetylglucosamine (alphaGlcNAc) residues largely attached to a MUC6 scaffold.
      Previously, we generated A4gnt-deficient mice, which totally lack alphaGlcNAc,
      and showed that alphaGlcNAc functions as a tumor suppressor for gastric cancer.
      Here, to determine the clinicopathological significance of alphaGlcNAc in gastric
      carcinomas, we examined immunohistochemical expression of alphaGlcNAc and mucin
      phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric
      adenocarcinomas and compared those expression patterns with clinicopathological
      parameters and cancer-specific survival. The alphaGlcNAc loss was evaluated in
      MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type
      gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked alphaGlcNAc
      expression. Loss of alphaGlcNAc was significantly correlated with depth of
      invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss
      of alphaGlcNAc was also significantly associated with poorer patient prognosis in
      MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant
      correlation between alphaGlcNAc loss and any clinicopathologic variable was
      observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also
      significantly correlated with several clinicopathological variables in
      differentiated-type adenocarcinoma. However, unlike the case with alphaGlcNAc,
      its expression showed no correlation with cancer-specific survival in patients.
      In undifferentiated-type adenocarcinoma, we observed no significant correlation
      between mucin phenotypic marker expression, including MUC6, and any
      clinicopathologic variable. These results together indicate that loss of
      alphaGlcNAc in MUC6-positive cancer cells is associated with progression and poor
      prognosis in differentiated, but not undifferentiated, types of gastric
      adenocarcinoma.

PMID- 24138593
TI  - Assessing progress toward becoming a patient-centered medical home: an assessment
      tool for practice transformation.
AB  - OBJECTIVE: To describe the properties of the Patient-Centered Medical Home
      Assessment (PCMH-A) as a tool to stimulate and monitor progress among primary
      care practices interested in transforming to patient-centered medical homes
      (PCMHs). STUDY SETTING: Sixty-five safety net practices from five states
      participating in a national demonstration program for PCMH transformation. STUDY
      DESIGN: Longitudinal analyses of PCMH-A scores were performed. Scores were
      reviewed for agreement and sites were categorized over time into one of five
      categories by external facilitators. Comparisons to key activity completion rates
      and NCQA PCMH recognition status were completed. DATA COLLECTION/EXTRACTION
      METHODS: Multidisciplinary teams at each practice completed the 33-item self
      assessment tool every 6 months between March 2010 and September 2012. PRINCIPAL
      FINDINGS: Mean overall PCMH-A scores increased (7.2, March 2010, to 9.1,
      September 2012; [p < .01]). Increases were statistically significant for each of
      the change concepts (p < .05). Facilitators agreed with scores 82% of the time.
      NCQA-recognized sites had higher PCMH-A scores than sites that were not yet
      recognized. Sites that completed more transformation activities and progressed
      over defined tiers reported higher PCMH-A scores. Scores improved most in areas
      where technical assistance was provided. CONCLUSIONS: The PCMH-A was sensitive to
      change over time and provided an accurate reflection of practice transformation.

PMID- 24138594
TI  - Cervical radiofrequency neurotomy reduces central hyperexcitability and improves
      neck movement in individuals with chronic whiplash.
AB  - OBJECTIVE: This study aims to determine if cervical medial branch radiofrequency
      neurotomy reduces psychophysical indicators of augmented central pain processing
      and improves motor function in individuals with chronic whiplash symptoms.
      DESIGN: Prospective observational study of consecutive patients with healthy
      control comparison. SETTING: Tertiary spinal intervention centre in Calgary,
      Alberta, Canada. SUBJECTS: Fifty-three individuals with chronic whiplash
      associated disorder symptoms (Grade 2); 30 healthy controls. METHODS: Measures
      were made at four time points: two prior to radiofrequency neurotomy, and 1- and
      3-months post-radiofrequency neurotomy. Measures included: comprehensive
      quantitative sensory testing (including brachial plexus provocation test),
      nociceptive flexion reflex, and motor function (cervical range of movement,
      superficial neck flexor activity during the craniocervical flexion test). Self
      report pain and disability measures were also collected. One-way repeated
      measures analysis of variance and Friedman's tests were performed to investigate
      the effect of time on the earlier measures. Differences between the whiplash and
      healthy control groups were investigated with two-tailed independent samples t
      test or Mann-Whitney tests. RESULTS: Following cervical radiofrequency neurotomy,
      there were significant early (within 1 month) and sustained (3 months)
      improvements in pain, disability, local and widespread hyperalgesia to pressure
      and thermal stimuli, nociceptive flexor reflex threshold, and brachial plexus
      provocation test responses as well as increased neck range of motion (all P <
      0.0001). A nonsignificant trend for reduced muscle activity with the
      craniocervical flexion test (P > 0.13) was measured. CONCLUSIONS: Attenuation of
      psychophysical measures of augmented central pain processing and improved
      cervical movement imply that these processes are maintained by peripheral
      nociceptive input.

PMID- 24138595
TI  - Immunophenotypic and molecular features of 'cuplike' acute myeloid leukemias.
AB  - Nuclear invaginations, also referred to as fishmouth or cuplike nuclei, have long
      been identified in microgranular APL, myelomonocytic and monocytic AMLs. More
      recently, this typical morphological feature has been associated with NPM1 and
      FLT3 mutations, as well as with the lack of CD34 and HLA-DR expression. In this
      study, we retrospectively analyzed the morphologic, immunophenotypic,
      cytogenetic, and molecular features of 68 patients with AML. A cuplike nuclear
      invagination was detected in more than 10% of blast cells in 15 (22%) cases. Our
      data show that a cuplike morphology is associated with FLT3-ITD positivity, as
      well as with the loss of CD34 and HLA-DR expression. The results were not
      significantly modified when a higher cutoff of cuplike cells was used. Our
      results are not sufficient to suggest that cuplike AML could represent a distinct
      subtype, but further investigations could yield a better characterization of this
      feature in patients with AML. 

PMID- 24138596
TI  - Plaque At RISK (PARISK): prospective multicenter study to improve diagnosis of
      high-risk carotid plaques.
AB  - BACKGROUND: Patients with symptomatic carotid artery stenosis are at high risk
      for recurrent stroke. To date, the decision to perform carotid endarterectomy in
      patients with a recent cerebrovascular event is mainly based on degree of
      stenosis of the ipsilateral carotid artery. However, additional atherosclerotic
      plaque characteristics might be better predictors of stroke, allowing for more
      precise selection of patients for carotid endarterectomy. AIMS AND HYPOTHESIS: We
      investigate the hypothesis that the assessment of carotid plaque characteristics
      with magnetic resonance imaging, multidetector-row computed tomography
      angiography, ultrasonography, and transcranial Doppler, either alone or in
      combination, may improve identification of a subgroup of patients with < 70%
      carotid artery stenosis with an increased risk of recurrent stroke. METHODS: The
      Plaque At RISK (PARISK) study is a prospective multicenter cohort study of
      patients with recent (<3 months) neurological symptoms due to ischemia in the
      territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who
      are not scheduled for carotid endarterectomy or stenting. At baseline, 300
      patients will undergo magnetic resonance imaging, multidetector-row computed
      tomography angiography, and ultrasonography examination of the carotid arteries.
      In addition, magnetic resonance imaging of the brain, ambulatory transcranial
      Doppler recording of the middle cerebral artery and blood withdrawal will be
      performed. After two-years, imaging will be repeated in 150 patients. All
      patients undergo a follow-up brain magnetic resonance imaging, and there will be
      regular clinical follow-up until the end of the study. STUDY OUTCOMES: The
      combined primary end-point contains ipsilateral recurrent ischemic stroke or
      transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up
      brain magnetic resonance imaging.

PMID- 24138598
TI  - New approach for rotational dyssynchrony using three-dimensional speckle tracking
      echocardiography.
AB  - Left ventricular (LV) twist can be evaluated using two-dimensional speckle
      tracking echocardiography (2DSTE) by analyzing difference between apical and
      basal rotation. However, it is unable to evaluate global rotational dyssynchrony
      because it cannot assess mid-wall rotation. Recently developed three-dimensional
      STE (3DSTE) can investigate LV global rotational dyssynchrony. In this study, we
      investigated the role of torsion on the long-term effects of cardiac
      resynchronization therapy (CRT) using 3DSTE. We evaluated 43 patients by 3DSTE:
      12 CRT responders, 14 CRT nonresponders, and 17 healthy normal controls. Regional
      torsion and rotation were assessed using 3DSTE across 16 segments during CRT-off
      (native conduction) and CRT-on. The following parameters were calculated: global
      peak twist, Delta global peak twist (difference between CRT-on and CRT-off), and
      torsion delay index. The torsion delay index was considered to be the rotational
      energy lost by rotational dyssynchrony. Global peak twist did not show
      significant differences between the responders and nonresponders during CRT-off
      (4.0 +/- 3.4 degrees  vs. 2.8 +/- 2.3 degrees , P = 0.295), but it significantly
      improved in responders compared to nonresponders after CRT-on (5.4 +/- 3.5
      degrees  vs. 2.6 +/- 2.6 degrees , P = 0.029). The torsion delay index during CRT
      off was significantly higher in responders compared to nonresponders and normal
      controls (18.5 +/- 11.3 vs. 8.6 +/- 3.8 and 7.8 +/- 5.5, P = 0.010 and P = 0.004,
      respectively). The torsion delay index during CRT-off significantly correlated
      with the Delta global peak twist (r = 0.503, P = 0.009). Improvement in LV global
      peak twist, which is one of the mechanisms for the long-term effects of CRT
      correlated with the torsion delay index during native conduction that can only be
      calculated by 3DSTE.

PMID- 24138599
TI  - The intricate association between gut microbiota and development of type 1, type
      2 and type 3 diabetes.
AB  - It has been proposed that changes in the composition of gut microbiota contribute
      to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer's
      disease). The onset of these diseases is affected by complex interactions of
      genetic and several environmental factors. Alterations in gut microbiota in
      combination with specific diets can result in increased intestinal permeability
      leading via a continuous state of low-grade inflammation to the development of
      insulin resistance. Since a change in composition of gut microbiota is also
      suggested to be the underlying factor for the development of obesity, it is
      obvious to link gut microbiota with the pathogenesis of diabetes. In addition,
      insulin resistance in the brain has been recently associated with Alzheimer's
      disease. These new paradigms in combination with data from studies with
      prebiotics and probiotics may lead to a novel way to control and even prevent
      diabetes in general. 

PMID- 24138600
TI  - Perforating elastic fibers ('elastic fiber trapping') in the differentiation of
      keratoacanthoma, conventional squamous cell carcinoma and pseudocarcinomatous
      epithelial hyperplasia.
AB  - Keratoacanthoma (KA), an epithelial neoplasm occurring in sun-exposed skin of the
      elderly, is considered a well-differentiated form of conventional squamous cell
      carcinoma (SCC) that often follows a course of spontaneous regression.
      Distinguishing KA from conventional SCC or pseudocarcinomatous epithelial
      hyperplasia ensures proper diagnosis, treatment and management. For some time,
      perforating elastic fibers have been utilized in differentiating KA from SCC.
      This phenomenon may also occur in association with scars and hypertrophic lupus
      erythematosus (LE). To assess the diagnostic utility of perforating elastic
      fibers, we compared their incidence in KA, SCC, scars with overlying
      pseudocarcinomatous hyperplasia, hypertrophic LE, hypertrophic lichen planus (LP)
      and lichen simplex chronicus (LSC). A retrospective case search identified 359
      lesions and the presence of perforating elastic fibers was evaluated using
      routinely stained sections. This phenomenon was documented in all studied groups
      except hypertrophic LP. The incidence was found to be 71% in KA, 37% in SCC, and
      was lowest in inflammatory conditions with associated pseudocarcinomatous
      hyperplasia (hypertrophic LP 0%, hypertrophic LE 5.9% and LSC 28.2%). The
      observed frequency in pseudocarcinomatous hyperplasia overlying scars (57.8%) vs.
      KA (71%) was not statistically different. Although elastic fiber trapping has
      potential value as a diagnostic criterion for KA, dermatopathologists should
      consider its limitations. Its diagnostic utility was greatest in distinguishing
      KA from hypertrophic LE and hypertrophic LP. Conversely, elastic trapping is not
      helpful differentiating pseudocarcinomatous hyperplasia from recurrent/persistent
      KA following surgery.

PMID- 24138601
TI  - Interactive programs with preschool children bring smiles and conversation to
      older adults: time-sampling study.
AB  - BACKGROUND: Keeping older adults healthy and active is an emerging challenge of
      an aging society. Despite the importance of personal relationships to their
      health and well-being, changes in family structure have resulted in a lower
      frequency of intergenerational interactions. Limited studies have been conducted
      to compare different interaction style of intergenerational interaction. The
      present study aimed to compare the changes in visual attention, facial
      expression, engagement/behaviour, and intergenerational conversation in older
      adults brought about by a performance-based intergenerational (IG) program and a
      social-oriented IG program to determine a desirable interaction style for older
      adults. METHODS: The subjects of this study were 25 older adults who participated
      in intergenerational programs with preschool children aged 5 to 6 years at an
      adult day care centre in Tokyo. We used time sampling to perform a structured
      observation study. The 25 older participants of intergenerational programs were
      divided into two groups based on their interaction style: performance-based IG
      program (children sing songs and dance) and social-oriented IG program (older
      adults and children play games together). Based on the 5-minute video
      observation, we compared changes in visual attention, facial expression,
      engagement/behaviour, and intergenerational conversation between the performance
      based and social-oriented IG programs. RESULTS: Constructive behaviour and
      intergenerational conversation were significantly higher in the social-oriented
      IG programming group than the performance-based IG programming group (p<0.001).
      No significant differences were observed in frequency of smiles, however, when
      weighted smiling rate was used, smiles were significantly more frequently
      observed in the social-oriented IG programming group than the performance-based
      IG programming (p<0.05). The visual attention occurred between the generations
      was significantly higher in the performance-based IG programming group than the
      social-oriented IG programming group (p<0.05). CONCLUSIONS: Intergenerational
      programs with preschool children brought smiles and conversation to older adults.
      The social-oriented IG program allowed older adults to play more roles than the
      performance-based IG program. The intergenerational programs provide
      opportunities to fulfil basic human needs and reintegrate older adults into
      society. Further development of such beneficial programs is warranted. TRIAL
      REGISTRATION: UMIN-CTR clinical Trial: UMIN000010439.

PMID- 24138603
TI  - High-efficiency small-molecule-based organic light emitting devices with solution
      processes and oxadiazole-based electron transport materials.
AB  - We demonstrate high-efficiency small-molecule-based white phosphorescent organic
      light emitting diodes (PHOLEDs) by single-active-layer solution-based processes
      with the current efficiency of 17.3 cdA(-1) and maximum luminous efficiency of
      8.86 lmW(-1) at a current density of 1 mA cm(-2). The small-molecule based
      emitting layers are codoped with blue and orange phosphorescent dyes. We show
      that the presence of CsF/Al at cathodes not only improves electron transport in
      oxadiazole-containing electron transport layers (ETLs), but also facilitates
      electron injection through the reacted oxadiazole moiety to reduce interface
      resistance, which results in the enhancement of current efficiency. By selecting
      oxadiazole-based materials as ETLs with proper electron injection layer
      (EIL)/cathode structures, the brightness and efficiency of white PHOLEDs are
      significantly improved. 

PMID- 24138604
TI  - Effect of mesenchymal stem cells and extracts derived from the placenta on
      trophoblast invasion and immune responses.
AB  - Tightly regulated trophoblast invasion and immunomodulation at the feto-maternal
      interface is important during implantation and fetal development. Although
      trophoblasts as a pregnancy-specific cell has been reported to be a key factor
      capable of regulating certain events during implantation, however, its regulatory
      mechanisms are still unclear. In this study, we analyzed the effects of chorionic
      plate-derived mesenchymal stem cells (CP-MSCs) and human placenta extract (hPE)
      isolated from human normal placentas on trophoblasts invasion and immune
      responses. We investigated the effects of CP-MSCs, hPE treatment, and their
      combination on trophoblasts invasion and on T-cells suppression through human
      leukocyte antigen-G (HLA-G) expression. Trophoblasts invasion was significantly
      increased by co-culture of CP-MSCs or by hPE treatment (P<0.05), and enhanced by
      the combination of CP-MSCs and hPE treatment (P<0.05). The proliferation of T
      cells was decreased by co-culture of CP-MSCs and hPE treatment, whereas the
      population of regulatory T-cells was increased (P<0.05). Also, the dynamics
      alterations of multiple cytokines were observed in the culture supernatants of
      trophoblasts and T-cells depending on CP-MSCs co-culture and hPE treatment.
      Interestingly, the concentration of soluble HLA-G was increased by CP-MSCs co
      culture, by hPE treatment and by combination of them on trophoblasts and
      activated T-cells (P<0.05). These findings suggested that CP-MSCs and hPE can
      regulate trophoblasts invasion and T-cell by alteration of HLA-G expression.
      These results will provide understandings of trophoblasts invasion and the
      immunological network at the feto-maternal interface during pregnancy and
      contribute to the foundation of a new treatment strategy for pregnancy disorders.

PMID- 24138602
TI  - Fixing frataxin: 'ironing out' the metabolic defect in Friedreich's ataxia.
AB  - The metabolically active and redox-active mitochondrion appears to play a major
      role in the cellular metabolism of the transition metal, iron. Frataxin, a
      mitochondrial matrix protein, has been identified as playing a key role in the
      iron metabolism of this organelle due to its iron-binding properties and is known
      to be essential for iron-sulphur cluster formation. However, the precise function
      of frataxin remains elusive. The decrease in frataxin expression, as seen in the
      inherited disorder Friedreich's ataxia, markedly alters cellular and
      mitochondrial iron metabolism in both the mitochondrion and the cell. The
      resulting dysregulation of iron trafficking damages affects tissues leading to
      neuro- and cardiodegeneration. This disease underscores the importance of iron
      homeostasis in the redox-active environment of the mitochondrion and the
      molecular players involved. Unravelling the mechanisms of altered iron metabolism
      in Friedreich's ataxia will help elucidate a biochemical function for frataxin.
      Consequently, this will enable the development of more effective and rationally
      designed treatments. This review will focus on the emerging function of frataxin
      in relation to the observed alterations in mitochondrial iron metabolism in
      Friedreich's ataxia. Tissue-specific alterations due to frataxin loss will also
      be discussed, as well as current and emerging therapeutic strategies.

PMID- 24138605
TI  - Studying synaptic efficiency by post-hoc immunolabelling.
AB  - BACKGROUND: In terms of vesicular recycling, synaptic efficiency is a key
      determinant of the fidelity of synaptic transmission. The ability of a
      presynaptic terminal to reuse its vesicular content is thought to be a signature
      of synaptic maturity and this process depends on the activity of several proteins
      that govern exo/endocytosis. Upon stimulation, individual terminals in networks
      of cultured cerebellar granule neurons exhibit heterogeneous exocytic responses,
      which reflect the distinct states of maturity and plasticity intrinsic to
      individual synaptic terminals. This dynamic scenario serves as the substrate for
      processes such as scaling, plasticity and synaptic weight redistribution.
      Presynaptic strength has been associated with the activity of several types of
      proteins, including the scaffolding proteins that form the active zone cytomatrix
      and the proteins involved in presynaptic exocytosis. METHODS: We have combined
      fluorescence imaging techniques using the styryl dye FM1-43 in primary cultures
      of cerebellar granule cells with subsequent post-hoc immunocytochemistry in order
      to study synaptic efficiency in terms of vesicular release. We describe a
      protocol to easily quantify these results with minimal user intervention.
      RESULTS: In this study we describe a technique that specifically correlates
      presynaptic activity with the levels of presynaptic markers. This method involves
      the use of the styryl dye FM1-43 to estimate the release capacity of a synaptic
      terminal, and the subsequent post-hoc immunolabelling of thousands of individual
      nerve terminals. We observed a strong correlation between the release capacity of
      the nerve terminal and the levels of the RIM1alpha but not the Munc13-1 protein
      in the active zone. CONCLUSIONS: Our findings support those of previous studies
      and point out to RIM1alpha as a crucial factor in determining synaptic
      efficiency. These results also demonstrate that this technique is a useful tool
      to analyse the molecular differences underlying the heterogeneous responses
      exhibited by neuronal networks.

PMID- 24138606
TI  - Seronegative hepatitis C virus infection in patients with lymphoproliferative
      disorders.
AB  - It has been reported that hepatitis C virus (HCV) RNA may be present in serum
      and/or lymphoid cells in the absence of specific circulating antibodies. The
      current study analysed seronegative HCV infection in patients with
      lymphoproliferative disorders. We studied 77 anti-HCV-negative patients (45 male
      and 32 female, mean age 54.8 +/- 14.2 years) with various lymphoproliferative
      disorders. HCV-RNA was detected by RT-PCR in plasma, peripheral blood mononuclear
      cells (PBMC) and bone marrow. Furthermore, the presence of viral nonstructural
      protein 3 (NS3) was determined in PBMC and bone marrow by immunostaining. HCV-RNA
      was detectable in at least one compartment in 27 (35.1%) patients. Viral RNA was
      found in bone marrow in 22 patients (28.6%), in PBMC in 13 (16.9%) and in plasma
      in 10 (13%) patients. In nine patients, evidence of infection was confined to the
      bone marrow compartment. Viral load in HCV-RNA-positive plasma ranged from 15 to
      1.17 * 10(3) IU/mL. NS3 was detected in all but two HCV-RNA-positive bone marrow
      samples and in all but one HCV-RNA-positive PBMC samples. All 27 HCV-RNA-positive
      patients remained anti-HCV-negative when tested again after 6-12 months, but only
      four remained HCV-RNA positive. In conclusion, among patients with
      lymphoproliferative disorders, HCV can be present in plasma, PBMC and bone marrow
      despite the lack of circulating specific antibodies. Further studies are required
      to analyse the phenomenon of seronegative infection and to determine whether such
      patients are infectious.

PMID- 24138607
TI  - Ruthenium nanoparticles supported on CeO2 for catalytic permanganate oxidation of
      butylparaben.
AB  - This study developed a heterogeneous catalytic permanganate oxidation system with
      ceria supported ruthenium, Ru/CeO2 (0.80/00 as Ru), as catalyst for the first
      time. The catalytic performance of Ru/CeO2 toward butylparaben (BP) oxidation by
      permanganate was strongly dependent on its dosage, pH, permanganate concentration
      and temperature. The presence of 1.0 g L(-1) Ru/CeO2 increased the oxidation rate
      of BP by permanganate at pH 4.0-8.0 by 3-96 times. The increase in Ru/CeO2 dosage
      led to a progressive enhancement in the oxidation rate of BP by permanganate at
      neutral pH. The XANES analysis revealed that (1) Ru was deposited on the surface
      of CeO2 as Ru(III); (2) Ru(III) was oxidized by permanganate to its higher
      oxidation state Ru(VI) and Ru(VII), which acted as the co-oxidants in BP
      oxidation; (3) Ru(VI) and Ru(VII) were reduced by BP to its initial state of
      Ru(III). Therefore, Ru/CeO2 acted as an electron shuttle in catalytic
      permanganate oxidation process. LC-MS/MS analysis implied that BP was initially
      attacked by permanganate or Ru(VI) and Ru(VII) at the aromatic ring, leading to
      the formation of various hydroxyl-substituted and ring-opening products. Ru/CeO2
      could maintain its catalytic activity during the six successive runs. In
      conclusion, catalyzing permanganate oxidation with Ru/CeO2 is a promising
      technology for degrading phenolic pollutants in water treatment. 

PMID- 24138609
TI  - Novel solid-phase extraction for epimer-specific quantitation of ergot alkaloids
      in rye flour and wheat germ oil.
AB  - Ergot alkaloids and their epimer-specific determination have gained increasing
      importance for food safety. A solid-phase extraction and cleanup method based on
      sodium-neutralized strong cation exchange (Na(+)-SCX) was developed to quantitate
      12 priority ergot alkaloids in rye flour and wheat germ oil by HPLC fluorescence
      analysis. Sample preparation is achieved by omitting acidic and alkaline
      conditions enabling minimized epimerization, which is necessary to determine
      ergot alkaloids according to their natural distribution in foods. Ergot alkaloids
      are eluted from SCX-column by forming ion pairs using a sodium hexanesulfonate
      containing solution which prevents epimerization for at least 96 h. Method
      validation yielded recoveries of 80-120% (rye flour) and 71-96% (wheat germ oil)
      with a maximum limit of quantitation (LOQ) of 2.0 MUg kg(-1) per ergot alkaloid
      for both matrices. The applicability of the developed method was demonstrated by
      analyzing 16 samples from German retail markets: 9 rye flours (max 178 +/- 5 MUg
      kg(-1)) and, reported for the first time, 7 wheat germ oils (max 56.8 +/- 2.7 MUg
      kg(-1)) expressed as the sum of 12 ergot alkaloids. 

PMID- 24138610
TI  - Oncogenic ERBB3 mutations altering p.Val104 is rare in acute leukemias and non
      Hodgkin lymphomas.

PMID- 24138608
TI  - Implementation of evidence-based employment services in specialty mental health.
AB  - OBJECTIVE: Study a quality improvement approach for implementing evidence-based
      employment services at specialty mental health clinics. DATA SOURCES/STUDY
      SETTING: Semistructured interviews with clinicians and administrators before,
      during, and after implementation. Qualitative field notes, structured baseline
      and follow-up interviews with patients, semistructured interviews with patients
      after implementation, and administrative data. STUDY DESIGN: Site-level
      controlled trial at four implementation and four control sites. Hybrid
      implementation-effectiveness study with mixed methods intervention evaluation
      design. DATA COLLECTION/EXTRACTION METHODS: Site visits, in-person and telephone
      interviews, patient surveys, patient self-assessment. A total of 801 patients
      completed baseline surveys and 53 clinicians and other clinical key stakeholders
      completed longitudinal qualitative interviews. PRINCIPAL FINDINGS: At baseline,
      sites varied in the availability, utilization, and quality of supported
      employment. Each site needed quality improvement for this service, though for
      differing reasons, with some needing development of the service itself and others
      needing increased service capacity. Improvements in knowledge, attitudes,
      beliefs, and referral behaviors were evident in mid- and postimplementation
      interviews, though some barriers persisted. Half of patients expressed an
      interest in working at baseline. Patients at implementation sites were 2.3 times
      more likely to receive employment services during the study year. Those who had a
      service visit were more likely to be employed at follow-up than those who did
      not. CONCLUSIONS: Studies of implementation and effectiveness require mixed
      methods to both enhance implementation in real time and provide context for
      interpretation of complex results. In this study, a quality improvement approach
      resulted in superior patient-level outcomes and improved clinician knowledge,
      attitudes, and behaviors, in the context of substantial variation among sites.

PMID- 24138612
TI  - State of the field survey: spinal cord stimulator use by academic pain medicine
      practices.
AB  - OBJECTIVE: The concept of neuromodulation via the use of spinal cord stimulators
      (SCS) was first established over forty years ago. Since then, its popularity has
      grown as numerous studies have demonstrated its utility to reduce chronic pain,
      improve patient function, and reduce long-term health care costs. The aim of this
      study was to update the pain medicine community on the evolution of SCS practice
      trends in academic centers. DESIGN: Ninety-three pain medicine fellowship
      programs in the United States were identified from the Accreditation Council for
      Graduate Medical Education Website and were contacted to participate in an
      internet survey. A 37-item questionnaire was inspired by a previous study
      performed by Fanciullo et al. Questions focused on three main themes regarding
      SCS clinical application, namely demographics, education, and technical matters.
      RESULTS: Completed surveys were received from 50 institutions, all of which
      reported performing SCS interventions. Annual implants ranged from 0 to 150.
      Fellowship training was cited as the most valuable modality for learning
      implantation. Nearly all programs reported manufacturer representative
      participation during SCS procedures, with a minority of program directors
      discouraging their involvement in fellow education. SCS trials were performed
      exclusively on an outpatient basis. The average length for trials was 4-7 days.
      The most common indication for SCS implantation was failed back surgery syndrome,
      which also had the highest 2-year success rate. Post procedure, patients
      generally were followed up every 2-4 weeks for device reprogramming, which was
      performed by company representatives 92% of the time. CONCLUSION: Standardized
      SCS training is imperative as the implementation of neuromodulation therapy
      continues to increase.

PMID- 24138611
TI  - An improved catalyst system for the Pd-catalyzed fluorination of (hetero)aryl
      triflates.
AB  - The stable Pd(0) species [(1,5-cyclooctadiene)(L.Pd)2] (L = AdBrettPhos) has been
      prepared and successfully evaluated as a precatalyst for the fluorination of aryl
      triflates derived from biologically active and heteroaryl phenols, challenging
      substrates for our previously reported catalyst system. Additionally, this
      precatalyst activates at room temperature under neutral conditions, generates 1,5
      cyclooctadiene as the only byproduct, and leads to overall cleaner reaction
      profiles. 

PMID- 24138613
TI  - Low-cost tele-assessment system for home-based evaluation of reaching ability
      following stroke.
AB  - OBJECTIVE: Tele-assessment techniques can provide healthcare professionals with
      easily accessible information regarding patients' clinical progress. Recently,
      kinematic analysis systems have been used to assess rehabilitative outcomes in
      stroke patients. Kinematic systems, however, are not compatible with tele
      assessment. The objective of our study was to develop a tele-assessment system
      for acquiring kinematic data of forward reaching movements in stroke patients,
      with an emphasis on cost-effectiveness, portability, and ease of use. MATERIALS
      AND METHODS: We selected four healthy control participants and eight hemiplegic
      stroke patients for our study. The stroke patients were classified as Brunnstrom
      stage III, stage IV, or stage V. Our tele-assessment system used two three-axes
      accelerometers, a potentiometer, a multifunctional data acquisition card, and two
      computers. A standardized kinematic system was applied simultaneously to validate
      the measurements recorded by our tele-assessment system during five repetitions
      of forward reaching movements. RESULTS: The correlation coefficients of the
      reaching displacement, velocity, and acceleration measurements obtained using our
      tele-assessment system and the standardized kinematic system were 0.956, 0.896,
      and 0.727, respectively. Differences in the maximum reaching distance and the
      maximum reaching velocity of forward reaching movements were observed among the
      study groups. There were no significant differences in the time required to
      complete the testing session among the study groups. CONCLUSIONS: Our tele
      assessment system is valid for the evaluation of upper-extremity reaching ability
      in stroke patients. Further research is needed to investigate the feasibility of
      the use of the tele-assessment system in patients' homes.

PMID- 24138615
TI  - Help is in your pocket: the potential accuracy of smartphone- and laptop-based
      remotely guided resuscitative telesonography.
AB  - BACKGROUND: Ultrasound (US) examination has many uses in resuscitation, but to
      use it to its full effectiveness typically requires a trained and proficient
      user. We sought to use information technology advances to remotely guide US-naive
      examiners (UNEs) using a portable battery-powered tele-US system mentored using
      either a smartphone or laptop computer. MATERIALS AND METHODS: A cohort of UNEs
      (5 tactical emergency medicine technicians, 10 ski-patrollers, and 4 nurses) was
      guided to perform partial or complete Extended Focused Assessment with Sonography
      of Trauma (EFAST) examinations on both a healthy volunteer and on a US phantom,
      while being mentored by a remote examiner who viewed the US images over either an
      iPhone((r)) (Apple, Cupertino, CA) or a laptop computer with an inlaid depiction
      of the US probe and the "patient," derived from a videocamera mounted on the
      UNE's head. Examinations were recorded as still images and over-read from a Web
      site by seven expert reviewers (ERs) (three surgeons, two emergentologists, and
      two radiologists). Examination goals were to identify lung sliding (LS)
      documented by color power Doppler (CPD) in the human and to identify
      intraperitoneal (IP) fluid in the phantom. RESULTS: All UNEs were successfully
      mentored to easily and clearly identify both LS (19 determinations) and IP fluid
      (14 determinations), as assessed in real time by the remote mentor. ERs confirmed
      IP fluid in 95 of 98 determinations (97%), with 100% of ERs perceiving clinical
      utility for the abdominal Focused Assessment with Sonography of Trauma. Based on
      single still CPD images, 70% of ERs agreed on the presence or absence of LS. In
      16 out of 19 cases, over 70% of the ERs felt the EFAST exam was clinically
      useful. CONCLUSIONS: UNEs can confidently be guided to obtain critical findings
      using simple information technology resources, based on the
      receiving/transmitting device found in most trauma surgeons' pocket or briefcase.
      Global US mentoring requires only Internet connectivity and initiative.

PMID- 24138617
TI  - The bioanalytical recession continues.

PMID- 24138620
TI  - Conference report: reviving pharmaceutical R&D with translational science,
      regulatory efficiency and innovative models.
AB  - The 4th Annual Shanghai Symposium on Clinical & Pharmaceutical Solutions through
      Analysis (CPSA Shanghai 2013) was held on 24-27 April 2013 in Shanghai, China.
      The meeting provided an educational forum for scientists from pharmaceutical
      industry, academia, CROs and instrument vendors to share experience and ideas,
      and discuss current challenges, issues and innovative solutions associated with
      pharmaceutical R&D. The meeting featured highly interactive events, including
      diversified symposia, roundtable discussions, workshops, poster sessions and
      conference awards. Education and specialized training are the foundation of CPSA
      events. The CPSA Shanghai 2013 meeting also featured an inaugural satellite
      workshop event in Beijing, as well as joint sessions traditionally held with
      local bioanalytical and drug metabolism discussion groups. 

PMID- 24138621
TI  - Detection and quantification of lysine acetyl-alteration using antibody
      microarray.
AB  - BACKGROUND: Lysine acetylation is a reversible and dynamic post-translational
      modification on proteins, and plays an important role in diverse biological
      processes. Technological limitations have so far prevented comparative
      quantification of lysine acetylation in different samples. RESULTS: We developed
      a method to efficiently study lysine acetylation on individual proteins from
      complex mixtures, using antibody microarrays to capture individual proteins
      followed by detection with lysine acetyl antibody. By profiling both protein and
      acetylation variations in multiple samples using this microarray, we found cancer
      associated lysine acetylation alteration on VEGF in the serum of hepatocellular
      carcinoma patients. CONCLUSION: Microarrays of lysine acetylation are highly
      effective for detecting acetylation, and should be useful in identifying and
      validating disease-associated acetylation alterations as biomarkers under both
      normal and pathological circumstances.

PMID- 24138622
TI  - High-throughput bioanalysis of bile acids and their conjugates using UHPLC
      coupled to HRMS.
AB  - BACKGROUND: Quantitative assessment of bile acids in biological matrixes is of
      growing interest, primarily due to hepatic toxicity resulting from drug
      interactions with the bile salt export pump. Nevertheless, many bile acids
      demonstrate poor fragmentation in MS, making conventional MS/MS not a good match
      for their selective quantitation in biological matrices. RESULTS: The current
      study was designed to evaluate the feasibility of simultaneous quantitation of 19
      bile acids using HRMS coupled to UHPLC separation with minimal instrument
      optimization. An effective chromatography was developed using an Agilent
      Zorbax((r)) Eclipse XDB-C18 column (1.8 um, 50 x 2.1 mm internal diameter),
      achieving separation of 19 compounds in 10 min. Excellent assay reproducibility
      was demonstrated, with two sets of standard curves, run 42 days apart.
      CONCLUSIONS: The results show that LC-HRMS is a viable platform for high
      throughput bioanalysis of bile acids especially in a drug-discovery setting.

PMID- 24138623
TI  - Universal immunogenicity validation and assessment during early biotherapeutic
      development to support a green laboratory.
AB  - BACKGROUND: Immunogenicity support during nonclinical biotherapeutic development
      can be resource intensive if supported by conventional methodologies. A universal
      indirect species-specific immunoassay can eliminate the need for biotherapeutic
      specific anti-drug antibody immunoassays without compromising quality. By
      implementing the R's of sustainability (reduce, reuse, rethink), conservation of
      resources and greener laboratory practices were achieved in this study. RESULTS:
      Statistical analysis across four biotherapeutics supported identification of
      consistent product performance standards (cut points, sensitivity and reference
      limits) and a streamlined universal anti-drug antibody immunoassay method
      implementation strategy. CONCLUSION: We propose an efficient, fit-for-purpose,
      scientifically and statistically supported nonclinical immunogenicity assessment
      strategy. Utilization of a universal method and streamlined validation, while
      retaining comparability to conventional immunoassays and meeting the industry
      recommended standards, provides environmental credits in the scientific
      laboratory. Collectively, individual reductions in critical material consumption,
      energy usage, waste and non-environment friendly consumables, such as plastic and
      paper, support a greener laboratory environment.

PMID- 24138624
TI  - Validation of hepcidin quantification in plasma using LC-HRMS and discovery of a
      new hepcidin isoform.
AB  - BACKGROUND: Hepcidin, a 25 amino acid peptide, plays an important role in iron
      homeostasis. Some hepcidin truncated peptides have antibiotic effects. RESULTS: A
      new analytical method for hepcidin determination in human plasma using LC-HRMS
      operating in full-scan acquisition mode has been validated. The extraction
      consists of protein precipitation and a drying reconstitution step; a 2.1 x 50 mm
      (idxL) C18 analytical column was used. Detection specificity, stability,
      accuracy, precision and recoveries were determined. The LOQ/LOD were 0.25/0.1 nM,
      respectively. More than 600 injections of plasma extracts were performed,
      allowing evaluation of the assay robustness. Hepcidin-20, hepcidin-22 and a new
      isoform, hepcidin-24, were detected in patients. CONCLUSION: The data underscore
      the usefulness of LC-HRMS for in-depth investigations related to hepcidin levels
      and pathways.

PMID- 24138625
TI  - A rapid and sensitive LC-ESI-MS/MS method for the detection of YF-49-92.MLS in
      rat plasma.
AB  - BACKGROUND: YF-49-92.MLS is a novel candidate for TB treatment. An accurate,
      precise and specific LC-MS/MS method for the quantification of YF-49-92.MLS in
      rat plasma using verapamil as an IS is reported in this paper. METHODOLOGY:
      Proper retention time and excellent peak shape were acquired using an Agilent
      Zorbax((r)) SB-C18 column with the mobile phase of 5 mmol/l ammonium acetate,
      0.1% formic acid-methanol (30:70, v/v). The LLOQ was 1 ng/ml. The calibration
      curves encompassed concentrations from 20 to 5000 ng/ml. Intra- and inter-assay
      precision and accuracy were within 15% by determining low, medium and high
      concentration samples. Extraction recovery, stability, and matrix effects were
      also fully validated. CONCLUSION: This method has been validated to be rapid and
      sensitive, and successfully applied to the PK study of YF-49-92.MLS in rat
      plasma.

PMID- 24138626
TI  - Quality by design for a vaccine release immunoassay: a case study.
AB  - BACKGROUND: As quality by design (QbD) for pharmaceutical product development is
      being expanded to include analytical methods, we applied QbD to the development
      of antigenicity assays measuring in vitro relative potency of a quadrivalent
      vaccine candidate. RESULTS: After establishing development targets together with
      customers, immunoassays were developed to meet objectives. Statistical design of
      experiments was used to optimize method parameters and establish a design space.
      Systematic risk analysis enabled identification of potential risks to method
      performance that were mitigated by investigating the available design space
      around risk factors and by establishing appropriate control strategies.
      CONCLUSION: We found QbD-based method development was a more efficient and
      systematic approach that could also potentially facilitate assay transfers and
      life cycle management.

PMID- 24138627
TI  - Microsample analyses via DBS: challenges and opportunities.
AB  - The use of DBS is an appealing approach to employing microsampling techniques for
      the bioanalysis of samples, as has been demonstrated for the past 50 years in the
      metabolic screening of metabolites and diseases. In addition to its minimally
      invasive sample collection procedures and its economical merits, DBS
      microsampling benefits from the very high sensitivity, selectivity and
      multianalyte capabilities of LC-MS, which has been especially well demonstrated
      in newborn screening applications. Only a few microliters of a biological fluid
      are required for analysis, which also translates to significantly reduced demands
      on clinical samples from patients or from animals. Recently, the pharmaceutical
      industry and other arenas have begun to explore the utility and practicality of
      DBS microsampling. This review discusses the basis for why DBS techniques are
      likely to be part of the future, as well as offering insights into where these
      benefits may be realized. 

PMID- 24138628
TI  - Recent developments in microfluidic chip-based separation devices coupled to MS
      for bioanalysis.
AB  - In recent years, the development of microfluidic chip separation devices coupled
      to MS has dramatically increased for high-throughput bioanalysis. In this review,
      advances in different types of microfluidic chip separation devices, such as
      electrophoresis- and LC-based microchips, as well as 2D design of microfluidic
      chip-based separation devices will be discussed. In addition, the utilization of
      chip-based separation devices coupled to MS for analyzing peptides/proteins,
      glycans, drug metabolites and biomarkers for various bioanalytical applications
      will be evaluated. 

PMID- 24138629
TI  - Recent advances in the bioanalytical applications of dried matrix spotting for
      the analysis of drugs and their metabolites.
AB  - DBS techniques for the bioanalysis of drugs and metabolites from whole blood have
      been demonstrated to be a useful tool in drug development. The term dried matrix
      spot (DMS) has been used to indicate that the DBS technique has been applied to
      nonblood matrices. DMS methods often employ a color-indicating process that
      enhances the ability to analyze these mostly transparent fluids when spotted onto
      collection paper. The color-indicating dye allows the analyst to visually confirm
      the location of the dried sample spot. Other benefits of using a color-indicating
      dye include improved method accuracy and precision, because the process of adding
      the dye allows for the concurrent addition of the IS prior to sample addition and
      extraction. To date, matrices that have been analyzed using DMS include
      cerebrospinal fluid, synovial fluid, saliva, tears, urine and plasma. 

PMID- 24138632
TI  - Electrospun TiO(2) fiber composite photoelectrodes for water splitting.
AB  - This work has focused on the development of electrospun TiO2 fiber composite
      photoelectrodes for hydrogen production by water splitting. For comparison,
      similar photoelectrodes were also developed using commercial TiO2 (Aeroxide P25)
      nanoparticles (NPs). Dispersions of either fibers or P25 NPs were used to make
      homogenous TiO2 films on fluorine-doped SnO2 (FTO) glass substrates by a doctor
      blade (DB) technique. Scanning electron microscopy (SEM) analysis revealed a much
      lower packing density of the DB fibers, with respect to DB-P25 TiO2 NPs; this was
      also directly reflected by the higher photocurrent measured for the NPs when
      irradiating the photoelectrodes at a light intensity of 1.5AM (1 sun, 1000
      W/m(2)). For a better comparison of fibers vs. NPs, composite photoelectrodes by
      dip-coating (onto FTO) TiO2 sol-gel (SG) matrixes containing an equal amount (5
      or 20 wt %) of either fibers or P25 NPs were also investigated. It emerged that
      the photoactivity of the fibers was significantly higher. For composites
      containing 5 wt % TiO2 fibers, a photocurrent of 0.5 mA/cm(2) (at 0.23 V vs
      Ag/AgCl) was measured, whereas 5 wt % P25 NPs only provided 0.2 mA/cm(2). When
      increasing to 20 wt % fibers or NPs, the photocurrent decreased, because of the
      formation of microcracks in the photoelectrodes, because of the shrinkage of the
      sol-gel. The high photoactivity of the fiber-based electrodes could be confirmed
      by incident photon to current efficiency (IPCE) measurements. Remarkably, the
      IPCE of composites containing 5 wt % fibers was between 35% and 40% in the region
      of 380-320 nm, and when accounting for transmission/reflection losses, the
      absorbed photon to current efficiency (APCE) was consistently over 60% between
      380 nm and 320 nm. The superior photoactivity is attributed to the enhanced
      electron transport in the electrospun fibers, with respect to P25 NPs. According
      to this study, it is clear that the electronic connectivity ensured by the sol
      gel also contributes positively to the enhanced photocurrent. 

PMID- 24138633
TI  - MASC is indistinguishable from acinic cell carcinoma, papillary-cystic variant on
      salivary gland FNA cytomorphology: case report with histological and
      immunohistochemical correlates.

PMID- 24138634
TI  - Structure-reactivity relationships of zwitterionic 1,3-diaza-Claisen
      rearrangements.
AB  - Bridged bicyclic tertiary allylic amines aza-norbornene 1 and isoquinuclidene 2
      add to isocyanates, isothiocyanates, and in situ-generated carbodiimides to form
      zwitterionic intermediates that undergo 1,3-diaza-Claisen rearrangements to
      afford highly substituted ureas, thioureas, and guanidines, respectively. Aza
      norbornene 1 is significantly more reactive toward 1,3-diaza-Claisen
      rearrangements than isoquinuclidene 2. This reactivity difference is most likely
      due to the inherent ring strain in the aza-bicyclo[2.2.1]heptene ring system of
      aza-norbornene 1. The most apparent reactivity trend of the heterocumulenes is
      that the most electron-deficient heterocumulenes are more reactive toward 1,3
      diaza-Claisen rearrangements. The introduction of a new stereocenter alpha- to
      the nucleophilic nitrogen in aza-norbornene 1 and isoquinuclidine 2 decreases the
      reactivity toward 1,3-diaza-Claisen rearrangements, while the exodiastereomers 3b
      and 4b are less reactive than the corresponding endodiastereomers 3a and 4a.
      Isocyanates that bear an electron-withdrawing group react with allylic amines 1
      3b to afford mixtures of ureas and isoureas; however, with excess isocyanate and
      heat, thermodynamic equilibration is possible affording ureas. Inspired by this
      observation, a one-pot reaction of isocyanates with amines 1, 2, and 3b followed
      by BF3.OEt2-catalyzed isomerization of the urea/isourea mixture was developed
      that affords the corresponding ureas in excellent yields. 

PMID- 24138635
TI  - Pathogenesis of alcohol-induced osteoporosis and its treatment: a review.
AB  - Osteoporosis is the most common bone disease in humans; it represents a major
      public health problem. This chronic disease is characterized by increase in bone
      fracture due to: reduced bone mass, deterioration of micro architectural and
      decreased bone strength, bone fragility; and bone mineral density 2.5 or more
      standard deviations below the normal mean. Secondary osteoporosis is a common
      cause of osteoporosis, and there are many underlying risk factors for
      osteoporosis. Chronic alcohol abuse is one of the modifiable risk factors in
      osteoporosis. There is evidence of correlation between chronic alcohol abuse and
      low bone mass. Alcohol is directly toxic to the bone; with increased incidence of
      fractures and complications. Although there is a paucity of studies regarding
      alcohol induced osteoporosis therapy, it can be classified into antiresorptive
      therapy and anabolic therapy. Bisphosphonates have been demonstrated to be
      clinically relevant to prevent bone damage associated with alcohol use while
      parathyroid hormone increased bone mineralization as well as bone formation in
      alcohol treated rats. Vitamin D supplementation could prevent bone toxicity in
      chronic drinkers. This review discussed the pathogenesis of alcohol-induced
      osteoporosis and the agents available for its treatment. Other potential
      therapies are also discussed. 

PMID- 24138636
TI  - Hsp27 as a therapeutic target in cancers.
AB  - Heat shock protein 27 (Hsp27), induced by heat shock, environmental and
      pathophysiological stressors, is a multidimensional protein that acts as a
      protein chaperone and an antioxidant. This protein plays a major role in the
      inhibition of apoptosis and actin cytoskeletal remodeling. This stress-activated
      protein is up-regulated in many cancers and is associated with poor prognosis as
      well as treatment resistance by protecting cells from therapeutic agent that
      normally induces apoptosis. This review highlights the most recent findings and
      role of Hsp27 in cancer and the different strategies to target and inhibit Hsp27
      for clinical purposes. 

PMID- 24138637
TI  - Anti-IL-12/23 in Crohn's disease: bench and bedside.
AB  - The heterodimeric cytokines IL-12 and IL-23 play a key role in T helper cell and
      innate lymphocyte cell differentiation and expansion. They are composed of a
      shared p40 chain, which pairs with a p35 or p19 chain to form IL-12 and IL-23,
      respectively. Preclinical model systems have predicted an important role of the
      p40 chain in intestinal inflammation. Moreover, genome-wide association studies
      have revealed that variants of the gene encoding the IL-23 receptor, as well as
      the locus harboring the gene encoding the p40 chain, confer genetic risk for
      developing Crohn's disease (CD) and ulcerative colitis (UC). Two monoclonal
      antibodies neutralizing the p40 chain (ustekinumab and briakinumab) and hence
      blocking both IL-12 and IL-23 activity, have been developed, which demonstrated
      clinical benefit in early phase trials, and hinted towards efficacy in a
      subpopulation of patients with CD who had failed prior anti-TNF antibody
      treatment. A dedicated phase 3 clinical trial of ustekinumab in patients
      suffering from moderate-to-severe CD who had previously failed anti-TNF antibody
      treatment indeed demonstrated a significant benefit over placebo for clinical
      response, but not remission, in this particularly difficult to treat patient
      population. Here we review the immunological and genetic background to anti-IL
      12/IL-23-directed therapeutic strategies, and the lessons that can be learned
      from results of these and related clinical trials that tackle associated
      biological pathways. 

PMID- 24138638
TI  - Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced
      central activation of adrenomedullary outflow in the rat.
AB  - BACKGROUND AND PURPOSE: Haemopressin and RVD-haemopressin, derived from the
      haemoglobin alpha-chain, are bioactive peptides found in brain and are ligands
      for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the
      secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by
      i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin
      derived peptides on this bombesin-induced response EXPERIMENTAL APPROACH:
      Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived
      peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines
      were subsequently measured electrochemically after HPLC. Direct effects of
      bombesin on secretion of adrenal catecholamines were examined using bovine
      adrenal chromaffin cells. Furthermore, activation of haemoglobin alpha-positive
      spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN,
      a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was
      assessed by immunohistochemical techniques. KEY RESULTS: Bombesin given i.c.v.
      dose-dependently elevated plasma catecholamines whereas incubation with bombesin
      had no effect on spontaneous and nicotine-induced secretion of catecholamines
      from chromaffin cells. The bombesin-induced increase in catecholamines was
      inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but
      not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin
      activated haemoglobin alpha-positive spinally projecting neurons in the PVN.
      CONCLUSIONS AND IMPLICATIONS: The haemoglobin-derived peptide RVD-haemopressin in
      the brain plays an inhibitory role in bombesin-induced activation of central
      adrenomedullary outflow via brain CB1 receptors in the rat. These findings
      provide basic information for the therapeutic use of haemoglobin-derived peptides
      in the modulation of central adrenomedullary outflow.

PMID- 24138640
TI  - Hope and connection: the experience of family caregivers of persons with dementia
      living in a long term care facility.
AB  - BACKGROUND: Hope is a psychosocial resource that is essential for the
      psychological, spiritual, and physical well-being of family members caring for
      persons with dementia. A significant positive relationship has been found between
      hope and well-being in family caregivers of persons with dementia living in the
      community. However, the hope experience of family caregivers of persons living
      with dementia in long-term care (LTC) facilities has not been explored. The
      purpose of this study was to explore the hope experience of family caregivers of
      persons with dementia living in a LTC facility. METHODS: Twenty-three open-ended
      face to face interviews were conducted with 13 family caregivers of residents
      with dementia in a LTC facility. Family was broadly defined to include relatives
      and friends. Seven of these participants also reflected on their hope in diaries
      over a two week period. Interview transcripts and journal texts were analyzed
      using Thorne's interpretive description approach. RESULTS: The over-arching theme
      was "hope and connection". Participants lost hope and felt despair when they
      perceived they were unable to connect with their family member in the LTC
      facility. They regained their hope when a connection could be made. Several sub
      themes were identified including: accepting where we are, living life in the
      moment, believing in something, standing together, and balancing dual worlds.
      CONCLUSIONS: Hope was important and essential for family caregivers of persons
      with dementia residing in a LTC facility. The overarching theme of "hope and
      connection" underscores the importance of maintaining relationships and
      connection between family members and the person in LTC. Given the paucity of
      hope research conducted within this population, the study findings provide a
      foundation for future research.

PMID- 24138639
TI  - Brain region-specific changes in N-acylethanolamine contents with time of day.
AB  - The N-acylethanolamines (NAEs) exert important behavioral, physiological, and
      immunological effects through actions at cannabinoid and other receptors. We
      measured concentrations of three NAEs, the Km and Vmax for fatty acid amide
      hydrolysis (FAAH), FAAH protein and FAAH mRNA in prefrontal cortex, hippocampus,
      hypothalamus, amygdala, striatum, and cerebellum at 4 h intervals, starting at
      03:00. Significant differences in N-arachidonylethanolamine contents among the
      times examined occur in the prefrontal cortex (PFC), hippocampus, hypothalamus,
      and striatum. N-Oleoylethanolamine concentrations exhibit large fluctuations over
      the day in the cerebellum, including a threefold decrease between 19:00 and
      23:00. N-Palmitoylethanolamine and N-oleoylethanolamine were significantly,
      positively correlated in all regions examined except the hypothalamus. FAAH Km
      values are significantly affected by time of day in PFC, hippocampus and amygdala
      and FAAH Vmax values are significantly affected in PFC, hippocampus and
      cerebellum. However, correlational data indicate that FAAH does not play a
      primary role in the circadian regulation of the NAE concentrations. FAAH protein
      expression is not significantly different among the harvest times in any brain
      region examined. Concentrations of 2-arachidonoylglycerol are significantly
      affected by time of harvest in the striatum and cerebellum, but not in other
      brain regions. Together, these data indicate that the NAEs exhibit diverse
      patterns of change with time of day that are likely the result of alterations in
      biosynthesis, and support the hypothesis that N-arachidonylethanolamine is a
      tonic activator of cannabinoid receptor signaling.

PMID- 24138641
TI  - Don't end up in the fields: identity construction among Mexican adolescent
      immigrants, their parents, and sociocontextual processes.
AB  - This grounded theory study of 16 Mexican immigrant adolescents and 20 of their
      parents examines how they construct relational identities within their families,
      at school, with friends, and in the larger society. Results focus on a core
      identity bind faced by the adolescents: immigration messages from parents that
      say, "don't be like me" and the societal message, "you're not like us." Response
      to this bind was guided by two contrasting sets of identity narratives:
      Empowering narratives invited an intentional approach to school and life choices.
      Restricting narratives maintained an ambivalent approach to school and life
      choices. Resolution of the identity bind was a collective, ongoing process that
      has implications for Mexican immigrant families and the professionals who work
      with them. 

PMID- 24138643
TI  - Ethical, legal and social implications of rare diseases and orphan drugs in
      Europe: meeting report of a Brocher symposium.
AB  - Ethical, legal and social implications of rare diseases and orphan drugs in
      Europe (Brocher symposium) Geneva, Switzerland 18-19 April 2013 As part of the
      Scientific Program of the Fondation Brocher, a two-day symposium on orphan drugs
      and rare diseases was held on the shores of Lac Leman in Geneva. Specific focus
      was on the ethical, legal and social implications of rare diseases and orphan
      drugs in Europe. The symposium gathered about 30 international stakeholders and
      experts, representing different scientific disciplines, the pharmaceutical
      industry and patient representatives. 

PMID- 24138644
TI  - Outpatient palliative care effectiveness: both patients and caregivers can gain.
AB  - Outpatient palliative care services are increasing in their effectiveness
      worldwide, because they can better focus on both patients' and caregivers' needs
      at all stages of the disease requiring this type of interventions. This was
      demonstrated before by various studies that,however, were performed mostly on
      patients with malignancies and thatyielded encouraging results about the severity
      of the symptoms and about the burden of care in the caregivers. In this analysis
      performed on a mixture of patients with malignant and nonmalignant diseases, Groh
      et al. demonstrate that the outpatient team intervention was able to reduce the
      severity of symptoms such as pain or digestive symptoms and were able to minimize
      the burden of care of the primary caregivers.

PMID- 24138645
TI  - Economic evaluations in European reimbursement submission guidelines: current
      status and comparisons.
AB  - This study aimed to review European national health-economic (HE) guidelines and
      to identify recent developments in guideline recommendations by comparing the
      findings with those of a review published in 2001. Guidelines were identified by
      searching websites of the Internal Society for Pharmacoeconomics and Outcomes
      Research (ISPOR) and government health insurance agencies, and by a literature
      review. National guidelines showed broad consistency in ranking clinical data
      sources and choice of comparators for HE analysis, but varied in recommended
      costs to be included, methods related to cost calculation and discounting. Many
      European countries have developed or revised national HE guidelines. The
      recommendations in these guidelines differ in some key aspects, limiting
      transferability of outcomes of HE evaluations. 

PMID- 24138646
TI  - The quality of economic studies of cancer pharmacogenomics: a quantitative
      appraisal of the evidence.
AB  - This study evaluated the quality of health economic studies of cancer
      pharmacogenomics (PGx). A systematic search of the literature for economic
      studies of PGx was conducted in four common cancers. Evaluation of study quality
      was carried out using the quality of health economic studies instrument. Thirty
      nine articles met our eligibility criteria and were selected and accepted for
      further statistical analyses. The majority of articles (85%) were studies
      focusing on breast cancer. The overall weighted mean quality score was 85.10,
      with a range from 21 to 100. Eighty-seven percent of articles were categorized as
      good quality, whereas some 10 and 3% were categorized as moderate and poor
      quality, respectively. The quality of economic studies of cancer PGx is generally
      good but varied widely. We identified several attributes that are predictive of
      quality. Our findings may be useful for oncologists, health economists and
      decision makers interested in evaluating studies involving PGx. 

PMID- 24138647
TI  - Major depressive disorder in Africa and the Middle East: a systematic literature
      review.
AB  - With major depressive disorder (MDD) associated with significant clinical,
      economic and health-related quality of life impact, we sought to systematically
      review and synthesize information relevant to the burden of MDD in Africa and the
      Middle East, from which published evidence is slim. Our literature search
      identified 54 publications assessing epidemiological (43), humanistic (5),
      clinical/treatment (7) or economic outcomes (2). General population MDD
      prevalence and that among chronic disease populations were similar in Africa and
      the Middle East. No MDD-related economic literature specific to Africa or the
      Middle East was identified. Five studies of humanistic outcomes were identified;
      four African studies documented significant reduction of health-related quality
      of life related to MDD. The frequency of certain risk factors for MDD, such as
      disease, trauma and associated stress, as well as patterns of MDD treatment,
      suggest the potential for a higher burden of disease in Africa and the Middle
      East than in western countries. 

PMID- 24138648
TI  - Conceptual, classification or causal: models of health status and health-related
      quality of life.
AB  - Instruments intended to assess health-related quality of life (HRQOL) and health
      status are widely used in research and clinical practice, but with little
      conceptual guidance there is some uncertainty about what it is that these
      instruments are actually tapping. Causal models have the potential to provide the
      required conceptual guidance, not only placing commonly discussed health concepts
      on a firm scientific foundation, but also allowing medical and psychosocial
      interventions to be developed in a more focused and efficient manner. Several
      models, some postulating causal relations, have been proposed over many years,
      and some have been supported by data. The development and validation of these
      models has, however, been conducted in a piecemeal fashion. The imperative to
      develop tailored, cost-effective interventions requires a synthesized approach to
      developing and testing causal models. 

PMID- 24138649
TI  - Impact of access restrictions on varenicline utilization.
AB  - AIM: To assess the impact of access restrictions on varenicline utilization.
      METHODS: Employer-sponsored health plans contributing to the MarketScan
      Commercial Claims and Encounters Database were categorized according to 2009
      varenicline access restrictions: no coverage; prior authorization; smoking
      cessation program requirement; no restrictions. The cohort comprised all adults
      continuously enrolled in plans during 2009. Each restriction cohort was compared
      with the no restrictions cohort using descriptive analyses. Data were assessed
      using logistic regression; demographic and clinical characteristics were
      covariates. RESULTS: In this study (no coverage, n = 454,419; prior
      authorization, n = 171,530; smoking cessation program, n = 108,181; no
      restrictions, n = 607,389), compared with the no restrictions cohort, the odds of
      treatment were 71% lower (odds ratio: 0.29; 95% CI: 0.26, 0.31) in the smoking
      cessation program cohort (p < 0.001) and 80% lower (odds ratio: 0.20; 95% CI:
      0.19, 0.22) in the prior authorization cohort (p < 0.001). CONCLUSIONS: Access
      restrictions were associated with significantly lower odds for varenicline
      utilization.

PMID- 24138650
TI  - A survey of individuals in US-based pharmaceutical industry HEOR departments:
      attitudes on policy topics.
AB  - We surveyed US-based leaders in health economics and outcomes research (HEOR)
      departments in drug and device companies to examine their views on the state of
      the field. We created a questionnaire that was emailed to 123 US-based senior
      HEOR professionals at 54 companies. Of the 123 recipients, 74 (60%) completed the
      survey. Most respondents (92%) expected their company's HEOR use to increase, and
      80% reported that their organization's senior management viewed HEOR work as
      critical. Approximately 62% agreed that Academy of Managed Care Pharmacy (AMCP)
      dossiers are useful to US health plans, and 55% stated that Food and Drug
      Administration Modernization Act (FDAMA) Section 114 is useful. Approximately 49%
      believed the US government should use cost-effectiveness analysis in coverage and
      reimbursement decisions, but only 31% expected this to occur within 3 years. The
      findings suggest strong support for the function at senior management levels and
      optimism about the field. 

PMID- 24138651
TI  - The burden of caring for dementia patients: caregiver reports from a cross
      sectional hospital-based study in China.
AB  - The impact of dementia care on caregivers' professional, personal, emotional and
      social well-being was measured in a cohort of 1,387 caregivers in seven regions
      across mainland China, using a Chinese version of the Zarit Burden Interview
      (ZBI) and four supplementary questions. Caregivers also estimated costs of care
      and medical resource utilization. Caregiver burden was generally low to moderate.
      Dementia care had the greatest impact on caregivers' professional lives, with
      25.5% reporting a reduced work schedule in the past month. Lost work time was
      greater for caregivers of patients with previously diagnosed dementia than for
      those with newly diagnosed dementia. Average monthly out-of-pocket costs of
      dementia care exceeded national average monthly incomes of rural and urban
      residents. These findings highlight the obstacles facing the country with the
      fastest-growing elderly population in the world. 

PMID- 24138652
TI  - Cost-effectiveness of 64-slice CT angiography compared to conventional coronary
      angiography based on a coverage with evidence development study in Ontario.
AB  - Conventional coronary angiography (CCA) is the standard diagnostic for coronary
      artery disease (CAD), but multi-detector computed tomography coronary angiography
      (CTCA) is a non-invasive alternative. METHODS: A multi-center coverage with
      evidence development study was undertaken and combined with an economic model to
      estimate the cost-effectiveness of CTCA followed by CCA vs CCA alone. Alternative
      assumptions were tested in patient scenario and sensitivity analyses. RESULTS:
      CCA was found to dominate CTCA, however, CTCA was relatively more cost-effective
      in females, in advancing age, in patients with lower pre-test probabilities of
      CAD, the higher the sensitivity of CTCA and the lower the probability of
      undergoing a confirmatory CCA following a positive CTCA. CONCLUSIONS: RESULTS
      were very sensitive to alternative patient populations and modeling assumptions.
      Careful consideration of patient characteristics, procedures to improve the
      diagnostic yield of CTCA and selective use of CCA following CTCA will impact
      whether CTCA is cost-effective or dominates CCA.

PMID- 24138654
TI  - Researching about research.

PMID- 24138653
TI  - X-ray crystal structure of bovine 3 Glu-osteocalcin.
AB  - The 3 Glu form of osteocalcin (3 Glu-OCN) is increased in serum during low
      vitamin K intake or oral anticoagulant use (warfarin). Previous reports using
      circular dichroism show it is less structured than 3 Gla Ca2+-osteocalcin and
      does not bind strongly to bone mineral. Recent studies have suggested a role for
      3 Glu-OCN as a potential regulator of glucose metabolism. A G-protein-coupled
      receptor, GPRC6a, found in the pancreas and testes was identified as the putative
      osteocalcin receptor. The purpose of this study is to determine the high
      resolution structure of bovine 3 Glu-OCN, using X-ray crystallography, to
      understand molecular interactions with mineral and the GPRC6a receptor.
      Diffraction quality crystals of thermally decarboxylated bovine osteocalcin were
      grown, and the crystal structure was determined to 1.88 A resolution. The final
      refined structure contained residues 17-47 and, like 3 Gla Ca2+-OCN, consisted of
      three alpha-helices surrounding a hydrophobic core, a C23-C29 disulfide bond
      between two of the helices, and no bound Ca2+. Thus, the helical structure of 3
      Glu-OCN is Ca2+-independent but similar to that of 3 Gla Ca2+-OCN. A reduced
      level of mineral binding could result from a lower number of Ca2+ coordinating
      ligands on 3 Glu-OCN. The structure suggests the GPRC6a receptor may respond to
      helical osteocalcin and will aid in providing molecular mechanistic insight into
      the role of 3 Glu-OCN in glucose homeostasis.

PMID- 24138655
TI  - The role of the Cochrane collaboration and nursing in evidence-based health care.
AB  - The Cochrane Collaboration has been instrumental in guiding evidence-based
      practice in health care over the last 20 years. There are many ways nurses can
      get involved with the Cochrane Collaboration and support the application of
      research evidence into best practices in health care. 

PMID- 24138657
TI  - An update on maternal mortality and morbidity in the United States.
AB  - Significant strides have been made in recent years to reduce maternal morbidity
      and mortality rates around the world. But in the United States, maternal
      mortality rates have increased from 6.6/100,000 live births in the 1980s and
      1990s to somewhere between 13.3/100,000 live births, as reported by the Centers
      for Disease Control and Prevention, and 21/100,000 live births, as reported by
      the World Health Organization. This article discusses factors influencing this
      trend, and explores organizations, systems and programs that have shown promise
      for reducing maternal morbidity and mortality. 

PMID- 24138658
TI  - A case study of recipient twin surviving complications of twin-to-twin
      transfusion syndrome.
AB  - Twin-to-twin transfusion syndrome (TTTS) has a high rate of mortality and
      morbidity. This article describes the clinical course of a recipient twin in a
      case of TTTS. The twin was on long-term respiration support and survived two
      resuscitations, pneumothorax, chest tube placement, blood exchange, necrotizing
      enterocolitis and corrective surgery. This case demonstrates that the effective
      use of a collaborative, multidisciplinary care approach between two hospitals can
      result in a newborn surviving a severe case of TTTS. 

PMID- 24138659
TI  - Applying lean management principles to the creation of a postpartum hemorrhage
      care bundle.
AB  - A lean management process is a set of interventions, each of which creates value
      for the customer. Lean management is not a new concept, but is relatively new to
      health care. Postpartum hemorrhage (PPH) is the most common cause of maternal
      death worldwide in both developing and developed countries. We applied lean
      management principles as an innovative approach to improving outcomes in patients
      with PPH. Initial results using principles of lean management indicated
      significant improvements in response time and family-centered care. When applied
      rigorously and throughout the organization, lean principles can have a dramatic
      effect on productivity, cost and quality. 

PMID- 24138660
TI  - Nurses share real-life research experiences.
AB  - Nursing for Women's Health convened a group of nurse researchers for a roundtable
      discussion about the relationship of research to the profession of nursing, how
      research drives evidence-based practice and how nurses can get involved in
      research and in its application to the care of women and newborns. 

PMID- 24138661
TI  - Evidence-based strategies for managing gestational diabetes in women with
      obesity.
AB  - Pregnancies complicated by both obesity and gestational diabetes mellitus (GDM)
      increase the risk of maternal and fetal complications, including but not limited
      to gestational hypertension, cesarean surgical birth, fetal macrosomia and
      postpartum hemorrhage. Because of the increased maternal and fetal risks
      associated with maternal obesity and GDM, the development of evidence-based
      strategies for screening for and management of GDM and for timing of birth will
      provide a comprehensive approach needed to optimize outcomes for both women and
      newborns. 

PMID- 24138662
TI  - Long-acting reversible contraception.
AB  - Although short-acting reversible hormonal contraceptives, such as oral
      contraceptives and the contraceptive patch and vaginal ring, remain the most
      commonly used contraceptive methods in the United States, they are also
      associated with the highest failure rates. Long-acting reversible contraception
      (LARC) methods, such as intrauterine devices and contraceptive implants, offer
      high continuation rates and very low failure rates, and are safe for use in most
      women. The provision of LARC methods to adolescent, young adult and nulliparous
      women is a relatively new concept that offers an innovative option for these
      populations. 

PMID- 24138663
TI  - Psychosocial impact of a cancer diagnosis during pregnancy.
AB  - Although a rare occurrence, cancer is sometimes diagnosed during or shortly after
      pregnancy. This article reviews two recent studies that specifically examine the
      psychosocial impact of a cancer diagnosis during pregnancy. Researchers have
      identified risk factors that may exacerbate women's anxiety, stress or distress
      during these co-occurring events. Nurses are in a unique position to support
      women dealing with a cancer diagnosis during pregnancy. 

PMID- 24138664
TI  - New pharmacologic treatments for familial hypercholesterolemia.
AB  - Familial hypercholesterolemias are a group of genetic disorders that cause high
      levels of low-density lipoprotein (LDL) cholesterol, which can lead to
      atherosclerosis and premature coronary heart disease. Heart disease is the
      leading cause of death in U.S. women. A major goal in prevention of
      cardiovascular disease is identification and modification of risk factors.
      Lomitapide and mipomersen are two new pharmacologic options for treatment of
      familial hypercholesterolemia. Both are indicated as an adjunct for the
      management of homozygous familial hypercholesterolemia, along with lipid-lowering
      medications and diet modification. 

PMID- 24138665
TI  - Resources for the health insurance marketplace.

PMID- 24138667
TI  - A time to be born and a time to die.

PMID- 24138668
TI  - Loss of aryl hydrocarbon receptor promotes gene changes associated with premature
      hematopoietic stem cell exhaustion and development of a myeloproliferative
      disorder in aging mice.
AB  - Loss of immune function and increased hematopoietic disease are among the most
      clinically significant consequences of aging. Hematopoietic stem cells (HSCs)
      from mice lacking aryl hydrocarbon receptor (AhR) have high rates of cell
      division. Studies were designed to test the hypothesis that aging AhR-null allele
      (AhR-KO) mice develop premature HSC exhaustion, and changes leading to
      hematological disease. Compared to wild-type, aging AhR-KO mice showed a
      decreased survival rate, splenomegaly, increased circulating white blood cells,
      hematopoietic cell accumulation in tissues, and anemia. Analysis of bone marrow
      indicated increased numbers of stem/progenitor and lineage-committed cells, but
      decreased erythroid progenitors. There was also decreased self-renewal capacity
      of HSCs determined by competitive repopulation and serial transplantation. HSCs
      also showed increased levels of reactive oxygen species (ROS), Ki-67, and gamma
      H2A.X, but decreased p16(Ink4a). Splenic cells from aging KO mice had abnormal
      expression of genes, including Gata-1, Sh2d3c, Gfi-1, p21, and c-myc, involved in
      trafficking and associated with leukemia. HSCs from AhR-KO mice had gene changes
      related to HSC maintenance and consistent with phenotype observed. The most
      prominent gene changes (overexpression of Srpk2, Creb1, Hes1, mtor, pdp1) have
      been associated with HSC hyperproliferation, leukemia, and accelerated aging.
      Pathway analyses also indicated an enrichment of genes associated with oxidative
      stress, acute myelogenous leukemia, aging, and heat shock response, and the beta
      catenin/Wnt pathways. These data indicate that loss of AhR and associated changes
      in multiple signaling pathways promote premature HSC exhaustion and development
      of a myeloproliferative disorder. They also implicate a critical role of the AhR
      in the regulation of HSCs. 

PMID- 24138669
TI  - Surveillance of pneumococcal serotype 1 carriage during an outbreak of serotype 1
      invasive pneumococcal disease in central Australia 2010-2012.
AB  - BACKGROUND: An outbreak of serotype 1 invasive pneumococcal disease (IPD)
      occurred in Central Australia from October 2010 to the latter part of 2012.
      Surveillance of serotype 1 carriage was conducted to determine epidemiological
      features of asymptomatic carriage that could potentially be driving the outbreak.
      METHODS: 130 patients and accompanying persons presenting at Alice Springs
      Hospital Emergency Department consented to nasopharyngeal swab (NPS) collection.
      NPS were processed by standard methods, including culture, pneumococcal lytA
      quantitative real-time PCR, serotype 1-specific real-time PCR and multi-locus
      sequence typing (MLST). RESULTS: Pneumococcal carriage was detected in 16% of
      participants. Carriage was highest in the under 10 year olds from remote
      communities surrounding Alice Springs (75%). Four NPS were positive for serotype
      1 DNA by PCR; 3 were also culture-positive for serotype 1 pneumococci. Serotype 1
      isolates had atypical colony morphology on primary culture. All serotype 1
      carriers were healthy children 5 to 8 years of age from remote communities. By
      MLST, serotype 1 isolates were ST306, as were IPD isolates associated with this
      outbreak. CONCLUSIONS: During an outbreak of serotype 1 ST306 IPD, carriage of
      the outbreak strain was detected in 3% NPS collected. All carriers were healthy
      children 5 to 8 years of age.

PMID- 24138670
TI  - Evaluation of the volatile composition and sensory properties of five species of
      microalgae.
AB  - Due to their high content of polyunsaturated fatty acids, antioxidants, and
      proteins, microalgae hold a lot of potential for nutritional applications. When
      microalgae are integrated into foodstuffs, the aroma is an important aspect to
      consider. In this study the aroma properties of microalgae were studied by
      correlating data on the volatile composition with sensory evaluations. Four
      species of marine microalgae ( Botryococcus braunii, , Rhodomonas , Tetraselmis
      species, and Nannochloropsis oculata ) and one fresh water microalga ( Chlorella
      vulgaris ) were investigated. Multivariate data processing revealed that
      microalgal samples having a seafood-like odor character contain high levels of
      sulfuric compounds (dimethyl disulfide, dimethyl trisulfide, and methional),
      diketones, alpha-ionone, and beta-ionone. Fresh green, fruity flavors were linked
      with typical aldehydes such as 2,4-alkadienals and 2,4,6-alkatrienals. The
      presence of these compounds in fresh microalga pastes is explained by aroma
      formation mechanisms such as enzymatic lipid oxidation, enzymatic and chemical
      degradation of dimethylsulfoniopropionate (generating dimethyl sulfide),
      phenylalanine (generating benzaldehyde), and carotenoids (generating ionones). 

PMID- 24138671
TI  - Endothelial cells do not arise from tumor-initiating cells in human
      hepatocellular carcinoma.
AB  - BACKGROUND: Conventional models of carcinogenesis suggest that tumors recruit
      blood vessel formation from normal host tissues. This concept has recently been
      challenged by prominent studies of glioblastoma, which suggest that intratumoral
      endothelial cells (ECs) may arise from cancer stem cells/tumor-initiating cells
      (TICs). Hepatocellular carcinoma (HCC) is a common, highly vascularized tumor
      with few effective therapies, against which anti-angiogenic strategies are being
      actively explored. TICs are felt to play a role in HCC pathobiology, but their
      contributions to tumor vasculature have not been studied. METHODS: We examined
      human HCCs in settings that selected for tumor formation from functionally
      defined TICs, and in which the origin of intratumoral ECs from TICs as opposed to
      host tissues could be clearly distinguished. We generated HCC nodules in the
      livers of immunodeficient mice by intrasplenic injection of HCC cells from cell
      lines and patient specimens and studied the tumor ECs by immunohistochemistry for
      mouse and human markers. We then used immunohistochemistry for EC markers in
      combination with fluorescence in situ hybridization (FISH) for X and Y
      chromosomes to study the endothelium of recurrent HCC specimens resected from sex
      mismatched liver allografts of patients who had undergone liver transplantation
      for HCC. RESULTS: We observed that all ECs in intrahepatic human HCC xenografts
      expressed mouse rather than human CD31. FISH analysis of recurrent HCCs resected
      from patients with sex-mismatched liver allografts revealed that all CD31+ and
      CD34+ intratumoral ECs originated from the donor allograft rather than the tumor.
      CONCLUSIONS: These observations suggest that the vasculature of human HCC arises
      from normal host tissues rather than from TICs, supporting ongoing efforts to
      target angiogenesis in HCC as it is currently understood, and suggesting that the
      contribution of TICs to the vasculature of other cancers is disease-specific.

PMID- 24138672
TI  - The burden of acute traumatic spinal cord injury among adults in the united
      states: an update.
AB  - The current incidence estimate of 40 traumatic spinal cord injuries (TSCI) per
      million population/year in the United States (U.S.) is based on data from the
      1990s. We sought to update the incidence and epidemiology of TSCI in U.S adults
      by using the Nationwide Emergency Department Sample (NEDS), the largest all-payer
      emergency department (ED) database in the United States. Adult ED visits between
      2007 and 2009 with a principal diagnosis of TSCI were identified using
      International Classification of Diseases (ICD)-9 codes (806.0-806.9 and 952.0
      952.9). We describe TSCI cumulative incidence, mortality, discharge disposition,
      and hospital charges weighted to the U.S. population. The estimated 3-year
      cumulative incidence of TSCI was 56.4 per million adults. Cumulative incidence of
      TSCI in older adults increased from 79.4 per million older adults in 2007 to 87.7
      by the end of 2009, but remained steady among younger adults. Overall, falls were
      the leading cause of TSCI (41.5%). ED charges rose by 20% over the study period,
      and death occurred in 5.7% of patients. Compared with younger adults, older
      adults demonstrated higher adjusted odds of mortality in the ED (adjusted odds
      ratio [AOR]=4.4; 95% confidence interval [CI]: 1.1-16.6), mortality during
      hospitalization (AOR=5.9; 95% CI: 4.7-7.4), and being discharged to chronic care
      (AOR=3.7; 95% CI: 3.0-4.5). The incidence of TSCI is higher than previously
      reported with a progressive increase among older adults who also experience worse
      outcomes compared with younger adults. ED-related TSCI charges are also
      increasing. These updated national estimates support the development of
      customized prevention strategies based on age-specific risk factors.

PMID- 24138673
TI  - The clinical impact of a false-positive urine cocaine screening result on a
      patient's pain management.
AB  - BACKGROUND: The urine of a patient admitted for chest and epigastric pain tested
      positive for cocaine using an immunoassay-based drug screening method
      (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial
      of recent cocaine use, this positive cocaine screening result in conjunction with
      a remote history of drug misuse impacted the patient's recommended pain therapy.
      Specifically, these factors prompted the clinical team to question the
      appropriateness of opioids and other potentially addictive therapeutics during
      the treatment of cancer pain from previously undetected advanced pancreatic
      carcinoma. OBJECTIVE: After pain management and clinical pathology consultation,
      it was decided that the positive cocaine screening result should be confirmed by
      gas chromatography-mass spectrometry (GC-MS) testing. RESULTS: This more
      sensitive and specific analytical technique revealed that both cocaine and its
      primary metabolite benzoylecgonine were undetectable (i.e., less than the assay
      detection limit of 50 ng/mL), thus indicating that the positive urine screening
      result was falsely positive. With this confirmation, the pain management service
      team was reassured in offering intrathecal pump (ITP) therapy for pain control.
      ITP implantation was well tolerated, and the patient eventually achieved
      excellent pain relief. However, ITP therapy most likely would not have been
      utilized without the GC-MS confirmation testing unless alternative options failed
      and extensive vigilant monitoring was initiated. CONCLUSION: As exemplified in
      this case, confirmatory drug testing should be performed on specimens with
      unexpected immunoassay-based drug screening results. To our knowledge, this is
      the first report of a false-positive urine cocaine screening result and its
      impact on patient management.

PMID- 24138675
TI  - Improving the accuracy of computed 13C NMR shift predictions by specific
      environment error correction: fragment referencing.
AB  - The accuracy of both Gauge-including atomic orbital (GIAO) and continuous set of
      gauge transformations (CSGT) (13)C NMR spectra prediction by Density Functional
      Theory (DFT) at the B3LYP/6-31G** level is shown to be usefully enhanced by
      employing a 'fragment referencing' method for predicting chemical shifts without
      recourse to empirical scaling. Fragment referencing refers to a process of
      reducing the error in calculating a particular NMR shift by consulting a similar
      molecule for which the error in the calculation is easily deduced. The absolute
      accuracy of the chemical shifts predicted when employing fragment referencing
      relative to conventional techniques (e.g., using TMS or MeOH/benzene dual
      referencing) is demonstrated to be improved significantly for a range of
      substrates, which illustrates the superiority of the technique particularly for
      systems with similar chemical shifts arising from different chemical
      environments. The technique is particularly suited to molecules of relatively low
      molecular weight containing 'non-standard' magnetic environments, e.g., alpha to
      halogen atoms, which are poorly predicted by other methods. The simplicity and
      speed of the technique mean that it can be employed to resolve routine structural
      assignment problems that require a degree of accuracy not provided by standard
      incremental or hierarchically ordered spherical description of environment (HOSE)
      algorithms. The approach is also demonstrated to be applicable when employing the
      MP2 method at 6-31G**, cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ levels, although none of
      these offer advantage in terms of accuracy of prediction over the B3LYP/6-31G**
      DFT method. 

PMID- 24138674
TI  - The expression of platelet serotonin transporter (SERT) in human obesity.
AB  - BACKGROUND: Serotonin (5-HT) is a well-known modulator of eating behavior.
      However, the molecular mechanisms linking its action to body weight balance have
      been only partially elucidated. Since platelets are a suitable peripheral model
      to study 5-HT transport, metabolism and release, we herein evaluated the
      expression of the platelet 5-HT re-uptake system (SERT) by [3H]-paroxetine
      binding assay. A cohort of 114 unrelated individuals (34 males, 80 females; age,
      mean +/- SD: 38.57 +/- 12.47 years) without major psychiatric disorders, was
      recruited following a naturalistic design regarding age or gender and classified
      accordingly to their body mass index (BMI). Subjects were divided into 5 groups:
      normal-weight (NW), overweight (OW) and grade I-III obese (OB) individuals. For
      gender analyses, data were transformed into [3H]-paroxetine density (Bmax)/BMI
      ratios to overcome both the disparity of women vs. men number and anthropometric
      differences between sexes. RESULTS: [3H]-paroxetine Bmax (SERT density, fmol/mg
      proteins) was reduced in platelet membranes of grade II (p < 0.01) and III (p <
      0.001) obese subjects vs. controls and in overweight subjects (p < 0.05) vs.
      grade III obese individuals. Considering all patients together, a strong negative
      correlation between Bmax and BMI (r = -0.449; P < 0.0001) was demonstrated.
      Conversely, [3H]-paroxetine KD (dissociation constant, nM) did not differ among
      groups. No gender-related variation concerning Bmax/BMI ratios was observed in
      this cohort of subjects. CONCLUSIONS: The down-regulation of SERT in platelet
      membranes of severe human obesity (BMI > 35 Kg/m2) confirms the involvement of 5
      HT system in body weight gain. Moreover, this findings may help to elucidate
      those monoamine-endocrine networks acting on fat storage, adipocyte signaling and
      energy balance. Targeting 5-HT/5-HT-related markers will possibly uncover the
      existence of human obesity subtypes.

PMID- 24138676
TI  - Parotid gland metastasis of breast cancer diagnosed on fine needle aspiration
      cytology: case report and review of literature.

PMID- 24138677
TI  - The prevalence of ocular lesions associated with hypertension in a population of
      geriatric cats in Auckland, New Zealand.
AB  - AIMS: To provide an estimate of the prevalence of ocular lesions associated with
      hypertension in geriatric cats in Auckland, New Zealand and to evaluate the
      importance of examination of the ocular fundi of cats over eight years of age.
      METHODS: A total of 105 cats >=8 years of age were examined and clinical signs
      recorded. Blood was collected for the laboratory measurement of the
      concentrations of blood urea nitrogen (BUN), glucose and creatinine in serum,
      urine was collected for determination of urine specific gravity (USG), and blood
      pressure (BP) was measured using high definition oscillometry equipment. A cat
      was determined to have systemic hypertension with a systolic BP >=160 mm Hg and a
      diastolic BP >=100 mm Hg. Each animal had an ocular fundic examination using a
      retinal camera to diagnose ocular lesions associated with hypertension, including
      retinopathies, choroidopathies and optic neuropathies. RESULTS: Blood pressure
      was successfully recorded in 73 cats. Of these, 37 (51%) had no hypertensive
      ocular lesions and no underlying disease diagnosed, 24 (33%) had no hypertensive
      ocular lesions detected, but underlying disease such as chronic kidney disease,
      hyperthyroidism or diabetes mellitus was diagnosed, and 12 (16%) cats had
      evidence of hypertensive ocular lesions. Ten of the cats with hypertensive ocular
      lesions were hypertensive at the time of the first visit and two were
      normotensive. One additional cat had hypertensive ocular lesions, but it was not
      possible to obtain consistent BP readings in this animal. Chronic kidney disease
      was the most commonly diagnosed concurrent disease in cats with hypertensive
      ocular lesions (n=6). Mean systolic BP for cats with hypertensive ocular lesions
      (168.0 (SE 6.29) mm Hg) was higher than for those with no ocular lesions (144.7
      (SE 3.11) mm Hg) or those with no lesions but with underlying disease (146.0 (SE
      4.97) mm Hg) (p=0.001). CONCLUSIONS: Ocular fundic examination of cats over eight
      years of age allows identification of cats with hypertensive ocular lesions,
      often before the owner or veterinarian is aware the cat has a problem with its
      vision. This may result in diagnosis of systemic hypertension allowing early
      treatment and resolution of lesions. CLINICAL RELEVANCE: The current study
      demonstrates that ocular lesions resulting from hypertension occur frequently
      enough in cats in Auckland to support the recommendation for fundic examination
      in cats over eight years of age as part of the routine physical examination.

PMID- 24138678
TI  - The effect of surgically assisted rapid maxillary expansion on sleep
      architecture: an exploratory risk study in healthy young adults.
AB  - Maxillary transverse deficiencies (MTD) cause malocclusions. Rapid maxillary
      expansion treatment is commonly used treatment for correcting such deficiencies
      and has been found to be effective in improving respiration and sleep
      architecture in children with obstructive sleep apnoea (OSA). However, thus far,
      the effect of surgically assisted rapid maxillary expansion (SARME) treatment on
      sleep architecture and breathing of normal subjects has not been assessed. We
      hypothesised that sleep quality will improve after maxillary expansion treatment.
      The objective of this study is to access the effect of maxillary expansion
      treatment on sleep structure and respiratory functions in healthy young adults
      with severe MTD. This is a prospective and exploratory clinical study. Twenty
      eight consecutive young adult patients (15 males and 13 females, mean age 20.6 +/
      5.8 years) presenting with severe MTD at the orthodontic examination were
      recruited into the study. All the participants underwent a standardised SARME
      procedure (mean expansion 6.5 +/- 1.8 and 8.2 +/- 1.8 mm, intercanine and
      intermolar distance, respectively) to correct malocclusion caused by MTD. An
      overnight in-laboratory polysomnography, before and after the treatment, was
      performed. The mean follow-up time was 9 months. The main outcome parameters were
      the changes in sleep architecture, including sleep stages, arousals, slow-wave
      activity (SWA) and respiratory variables. Before surgery, young adult patients
      with MTD presented no evidence of sleep breathing problems. At baseline sleep
      recording, 7 of 28 (25%) had apnoea-hypopnoea index (AHI) >= 5 events per hour.
      No negative effect of the SARME was observed in questionnaires or sleep
      laboratory parameters. In the patients with a higher baseline AHI (AHI >= 5 h of
      sleep), we observed a reduction in AHI after surgical treatment (P = 0.028).
      SARME did not have a negative effect on any sleep or respiration parameters in
      healthy young individuals with MTD. It normalised the breathing index in the
      patients with a mild AHI index. 

PMID- 24138679
TI  - Ag@Fe2O3-GO nanocomposites prepared by a phase transfer method with long-term
      antibacterial property.
AB  - Silver has been utilized as a highly effective and broad-spectrum antibacterial
      agent in our daily life. However, low stability, poor long-term antibacterial
      efficiency, and potential environmental hazard of released Ag(+) ions may limit
      its practical applications. Ag-graphene oxide (GO) nanocomposites have been
      reported to display highly enhanced antibacterial property, yet their stability
      and long-term antibacterial properties have not been carefully investigated.
      Herein, we report the synthesis of Ag@Fe2O3-GO nanocomposites with tunable
      loading density up to full monolayer coverage by adopting a simple phase transfer
      method. Compared to Ag@Fe2O3, its GO composite shows enhanced stability with
      Ag(+) releasing rate decreased by more than two times under dialysis condition.
      We discover that the presence of GO not only slows down Ag nanoparticle oxidation
      process but also enables Ag(+) ions recrystallization on GO surface. The Ag@Fe2O3
      GO nanocomposites have shown better and long-term antibacterial property against
      both Gram-negative and Gram-positive bacteria than those of plain Ag and
      Ag@Fe2O3, displaying great potential as a promising long-term bactericide with
      suppressed environmental hazard. 

PMID- 24138680
TI  - The association between family and community social capital and health risk
      behaviours in young people: an integrative review.
AB  - BACKGROUND: Health risk behaviours known to result in poorer outcomes in
      adulthood are generally established in late childhood and adolescence. These
      'risky' behaviours include smoking, alcohol and illicit drug use and sexual risk
      taking. While the role of social capital in the establishment of health risk
      behaviours in young people has been explored, to date, no attempt has been made
      to consolidate the evidence in the form of a review. Thus, this integrative
      review was undertaken to identify and synthesise research findings on the role
      and impact of family and community social capital on health risk behaviours in
      young people and provide a consolidated evidence base to inform multi-sectorial
      policy and practice. METHODS: Key electronic databases were searched (i.e. ASSIA,
      CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of
      Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline,
      PsycINFO, Sociological Abstracts) for relevant studies and this was complemented
      by hand searching. Inclusion/exclusion criteria were applied and data was
      extracted from the included studies. Heterogeneity in study design and the
      outcomes assessed precluded meta-analysis/meta-synthesis; the results are
      therefore presented in narrative form. RESULTS: Thirty-four papers satisfied the
      review inclusion criteria; most were cross-sectional surveys. The majority of the
      studies were conducted in North America (n=25), with three being conducted in the
      UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates
      that social capital is an important construct for understanding the establishment
      of health risk behaviours in young people. The different elements of family and
      community social capital varied in terms of their saliency within each
      behavioural domain, with positive parent-child relations, parental monitoring,
      religiosity and school quality being particularly important in reducing risk.
      CONCLUSIONS: This review is the first to systematically synthesise research
      findings about the association between social capital and health risk behaviours
      in young people. While providing evidence that may inform the development of
      interventions framed around social capital, the review also highlights key areas
      where further research is required to provide a fuller account of the nature and
      role of social capital in influencing the uptake of health risk behaviours.

PMID- 24138681
TI  - Perceptions community residents have about partner institutions and clinical
      research.
AB  - INTRODUCTION: Engaging community residents to obtain their feedback in conducting
      clinical research, and including them as leaders in implementing applicable
      health advances is crucial for success and sustaining large center awards.
      METHODS: Forty-four adult men and women participated in one of four focus groups.
      Two groups each (one African American and one Caucasian) were conducted in Baton
      Rouge and in New Orleans. RESULTS: In an effort to determine the knowledge,
      attitudes, and beliefs Louisiana residents have about the Louisiana Clinical and
      Translational Science (LA CaTS) Center concept, four main themes emerged from
      focus group participants concerning the state's research institutions, and what
      it means to have these institutions operating under one umbrella to improve the
      quality of health of its people: (1) academic/research institutions of the State
      are uniformly widely recognized and held in high regard; (2) increasing awareness
      of clinical research is a necessity; (3) establishing the LA CaTS Center is an
      excellent idea; and (4) effective communication including delivery style is
      crucial to partnerships and especially to the community. CONCLUSION: Focus group
      discussions can provide insight into community residents' perceptions, beliefs,
      motivations, and patterns of behavior for strategically planning for large center
      awards.

PMID- 24138682
TI  - Predicting cancer mortality: Developing a new cancer care variable using mixed
      methods and the quasi-statistical approach.
AB  - OBJECTIVE: To demonstrate the value of using a variable derived from qualitative
      analysis in subsequent quantitative analyses. DATA SOURCES/STUDY SETTING: Mixed
      methods data were combined with 10-year mortality outcomes. Participants with
      cancer were recruited from services at a large teaching hospital, and mortality
      data were from the Social Security Death Index. STUDY DESIGN: An observational
      concurrent or convergent mixed methods design was used to collect demographics
      and structured ratings along with qualitative data from 909 cancer patients at
      baseline. DATA COLLECTION/EXTRACTION METHODS: Coding rules for qualitative data
      were defined for open-ended responses from cancer participants speaking about
      their view of self, and a variable was numerically coded for each case. Mortality
      outcomes were matched to baseline data, including the view of self variable.
      PRINCIPAL FINDINGS: Individuals with an improved view of self had a significantly
      lower mortality rate than those for whom it was worse or unchanged, even when
      adjusting for age, gender, and cancer stage. CONCLUSIONS: Statistical analysis of
      qualitative data is feasible and can identify new predictors with health
      services' implications associated with cancer mortality. Future studies should
      consider the value of testing coded qualitative variables in relation with key
      health care outcomes.

PMID- 24138684
TI  - Deep brain stimulation for Parkinson's disease using frameless technology.
AB  - Historically deep brain stimulation (DBS) for Parkinson's disease (PD) has been
      performed by frame-based stereotaxy. However, recently the option of frameless
      stereotaxy has become available. This avoids the potential discomfort the patient
      may experience because of the frame fixed to the head. This study compared
      clinical outcomes of DBS performed using frame-based and frameless procedures for
      PD patients. Twelve patients underwent DBS operations; from these patients, six
      underwent frame-based and six underwent frameless DBS operations, and assessed 6
      months later. Operation time, subthalamic electrode contact length,
      microelectrode recording (MER) tracts, and unified PD rating scale scores were
      evaluated and the scores were compared. This small study found no differences
      between frameless or frame based DBS, and concludes that framless system maybe an
      acceptable alternative.

PMID- 24138683
TI  - Socioeconomic and family influences on dental treatment needs among Brazilian
      underprivileged schoolchildren participating in a dental health program.
AB  - BACKGROUND: The objective of this study was to compare the socioeconomic and
      family characteristics of underprivileged schoolchildren with and without
      curative dental needs participating in a dental health program. METHODS: A random
      sample of 1411 of 8-to-10 year-old Brazilian schoolchildren was examined and two
      sample groups were included in the cross-sectional study: 544 presented curative
      dental needs and the other 867 schoolchildren were without curative dental needs.
      The schoolchildren were examined for the presence of caries lesions using the
      DMFT index and their parents were asked to answer questions about
      socioenvironmental characteristics of their families. Logistic regression models
      were adjusted estimating the Odds Ratios (OR), their 95% confidence intervals
      (CI), and significance levels. RESULTS: After adjusting for potential
      confounders, it was found that families earning more than one Brazilian minimum
      wage, having fewer than four residents in the house, families living in homes
      owned by them, and children living with both biological parents were protective
      factors for the presence of dental caries, and consequently, curative dental
      needs. CONCLUSIONS: Socioeconomic status and family structure influences the
      curative dental needs of children from underprivileged communities. In this
      sense, dental health programs should plan and implement strategic efforts to
      reduce inequities in oral health status and access to oral health services of
      vulnerable schoolchildren and their families.

PMID- 24138685
TI  - Twelfth nerve paresis induced by an unusual posterior fossa arachnoid cyst: case
      report and literature review.
AB  - There are only three cases of arachnoid cysts inducing twelfth nerve paresis
      described in English medical literature. We herein report one more instance. Six
      weeks after surgery, the patient has almost fully recovered. This case underlines
      the importance of considering the arachnoid cyst as a possible cause of twelfth
      nerve paresis.

PMID- 24138686
TI  - Is rapid on-site evaluation during bronchoscopy useful?

PMID- 24138688
TI  - Combination ICS/fast-onset LABA inhaler as maintenance and reliever therapy: the
      future for uncontrolled adult asthma?
AB  - In the Single combination inhaler as Maintenance And Reliever Therapy (SMART)
      regimen, asthma patients use a corticosteroid/fast-onset long-acting beta-agonist
      inhaler as both regular maintenance and reliever therapy. In this multicenter,
      double-blind randomized controlled trial, Papi et al. have demonstrated that
      treatment with the combination beclometasone/formoterol hydrofluoroalkane (HFA)
      MDI when used as both maintenance and reliever therapy significantly prolongs the
      time to the first severe asthma exacerbation and reduces severe exacerbations
      compared with the same fixed dose of maintenance beclometasone/formoterol HFA-MDI
      with salbutamol MDI for relief. These findings are consistent with those of the
      prior studies of the SMART regimen with the budesonide/formoterol DPI and extend
      the evidence for use of the SMART regimen to the extrafine
      beclometasone/formoterol HFA-MDI, to patients with high baseline reliever use,
      and to patients in whom the SMART regimen results in a step up, step down or no
      change in baseline inhaled corticosteroid dose. 

PMID- 24138689
TI  - A 62-year-old female patient with left-sided pleural effusion.
AB  - Hepatic hydrothorax is defined as a pleural effusion in patients with liver
      cirrhosis without primary cardiac, pulmonary or pleural disease. It is a rare but
      important cause of unilateral-pleural effusion. The prevalence of this
      complication is 5-10% of the total number of patients with advanced stages of
      cirrhosis. In most cases (85%), the effusion is right-sided; however, in 13% of
      cases it can be left-sided and bilateral in 2% of the cases. We present a case of
      left-sided hepatic hydrothorax in the absence of ascites in a patient with
      primary biliary cirrhosis. The diagnosis of cirrhosis was confirmed by the
      biopsy;the patient didn't have any history or any signs or symptoms of cirrhosis
      prior to her presentation. In the case described, the patient was treated with
      spirnolactone, furosemide and ursodeoxycholic acid. At follow-up after six months
      since the diagnosis, she was responding to treatment with no complications. This
      case emphasizes the importance of considering hepatic hydrothorax as an etiology
      of a transudative pleural effusion regardless of the presence or absence of
      ascites inpatients with occult cirrhosis.

PMID- 24138690
TI  - The implication of telehealthcare in COPD management of China.
AB  - Chronic obstructive pulmonary disease (COPD) is a very common disease all around
      the world and has become an increasing public health concern to the Chinese
      medical community. In the past decades, telehealthcare technology has become a
      good way to manage COPD but current evidence makes it hard to determine the
      effectiveness of this technology. Internet of things (Iot) is a recent
      breakthrough in communication technology, which links the virtual world to the
      real world through connection between sensors and working devices. It relates
      people and items in any ways so that data collection and management become more
      flexible. Our review concentrates on the effectiveness and potential application
      of telehealthcare in COPD management and how IoT technology may stimulate COPD
      healthcare delivery through telehealthcare technology. 

PMID- 24138691
TI  - New treatment and markers of prognosis for idiopathic pulmonary fibrosis: lessons
      learned from translational research.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung
      disease with increasing prevalence, high mortality rates and poor treatment
      options. The diagnostic process is complex and often requires an
      interdisciplinary approach between different specialists. Information gained over
      the past 10 years of intense research resulted in improved diagnostic algorithms,
      a better understanding of the underlying pathogenesis and the development of new
      therapeutic options. Specifically, the change from the traditional concept that
      viewed IPF as a chronic inflammatory disorder to the current belief that is
      primarily resulting from aberrant wound healing enabled the identification of
      novel treatment targets. This increased the clinical trial activity dramatically
      and resulted in the approval of the first IPF-specific therapy in many countries.
      Still, the natural history and intrinsic behavior of IPF are very difficult to
      predict. There is an urgent need for new therapies and also for development and
      validation of prognostic markers that predict disease progression, survival and
      also response to antifibrotic drugs. This review provides an up to date summary
      of the most relevant clinical trials, novel therapeutic drug targets and outlines
      a spectrum of potential prognostic biomarkers for IPF. 

PMID- 24138692
TI  - Oxygen for end-of-life lung cancer care: managing dyspnea and hypoxemia.
AB  - Oxygen is commonly prescribed for lung cancer patients with advancing disease.
      Indications include hypoxemia and dyspnea. Reversal of hypoxemia in some cases
      will alleviate dyspnea. Oxygen is sometimes prescribed for non-hypoxemic patients
      to relieve dyspnea. While some patients may derive symptomatic benefit, recent
      studies demonstrate that compressed room air is just as effective. This raises
      the question as to whether to continue their oxygen. The most efficacious
      treatment for dyspnea is pharmacotherapy-particularly opioids. Adjunctive
      therapies include pursed lips breathing and a fan blowing toward the patient.
      Some patients may come to require high-flow oxygen. High-flow delivery devices
      include masks, high-flow nasal oxygen and reservoir cannulas. Each device has
      advantages and drawbacks. Eventually, it may be impossible or impractical to
      maintain a SpO2 > 90%. The overall goal in these patients is comfort rather than
      a target SpO2. It may eventually be advisable to remove continuous oximetry and
      transition focus to pharmacological management to achieve patient comfort. 

PMID- 24138693
TI  - Advances in pneumococcal antibiotic resistance.
AB  - Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been
      evolving with the widespread use of antibiotics and the introduction of
      pneumococcal conjugate vaccines (PCV). Particularly, among various types of
      antimicrobial resistance, macrolide resistance has most remarkably increased in
      many parts of the world, which has been reported to be >70% among clinical
      isolates from Asian countries. Penicillin resistance has dramatically decreased
      among nonmeningeal isolates due to the changes in resistance breakpoints,
      although resistance to other beta-lactams such as cefuroxime has increased.
      Multidrug resistance became a serious concern in the treatment of invasive
      pneumococcal diseases, especially in Asian countries. After PCV7 vaccination,
      serotype 19A has emerged as an important cause of invasive pneumococcal diseases
      which was also associated with increasing prevalence of multidrug resistance in
      pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and
      19A, may contribute to reduce the clonal spread of drug-resistant 19A
      pneumococci. 

PMID- 24138694
TI  - Advances in the management of pleural disease.
AB  - Pleural disease affects over 3000 people per million population annually.
      Consequently, it represents a significant proportion of the respiratory
      physician's workload and can present to clinicians of all backgrounds in primary
      and secondary care. Pleural effusions have been reported in association with over
      50 different conditions; some related to specific pulmonary pathologies, but many
      being manifestations of multisystem disease. The burden that conditions such as
      pleural infection; malignant pleural disease; and pneumothorax impose on patients
      and health care systems is enormous and growing. As such, a clear understanding
      of these key conditions is crucial to any physician regardless of the specialty.
      This article addresses a number of areas relating to pleural disease, providing
      an overview of the diagnostic and therapeutic advances that have been made in our
      understanding of pleural pathology in recent years. The directions that future
      research in this important area of respiratory medicine might take will also be
      discussed. 

PMID- 24138695
TI  - Update on the potential role of statins in chronic obstructive pulmonary disease
      and its co-morbidities.
AB  - Chronic obstructive pulmonary disease (COPD) is soon to become the third leading
      cause of death in developed countries. COPD is increasingly considered a
      multisystem disease characterized by both pulmonary and systemic inflammation.
      Over the last 5 years, there have been a growing number of studies showing that
      the cholesterol-lowering drugs statins (HMG-CoA reductase inhibitors) have a
      beneficial effect in patients with COPD. While statins are known to have a number
      of pharmacological effects (pleiotropy) that could explain these benefits, it is
      currently not clear which effects are most relevant in COPD. This article reviews
      the most recently published studies of statin therapy in patients with COPD,
      focusing on the important COPD co-morbidities of the pulmonary system (infective
      exacerbations, pneumonia, influenza and lung cancer) and cardiovascular system
      (acute coronary syndrome, endothelial dysfunction and pulmonary hypertension).
      While we await the results of randomized controlled trials, there continues to be
      consistent (albeit indirect) evidence from observational studies suggesting
      statins are beneficial for patients with COPD, conferring important
      pharmacological effects on inflammation not conferred by current inhaler-based
      therapies. 

PMID- 24138696
TI  - Noninvasive ventilation in pediatric emergency care: a literature review and
      description of our experience.
AB  - Noninvasive ventilation (NIV) refers to a kind of mechanical respiratory support
      used in order to avoid the progression of respiratory failure to endotracheal
      intubation. Even though if this method is widely known in patients affected by
      chronic diseases and in children admitted in pediatric and neonatal intensive
      care units, few data are actually available on its use in intermediate care
      units. The present review focuses on the efficiency of NIV performed in children
      with acute respiratory failure due to different conditions. Moreover, the authors
      have described their experience with NIV in pediatric patients admitted to their
      acute and emergency room where NIV was started, well tolerated and led to an
      improvement of gas exchanges, decreasing the muscular respiratory work and
      endotracheal intubation avoidance in most of the patients. 

PMID- 24138697
TI  - Host mucin glycosylation plays a role in bacterial adhesion in lungs of
      individuals with cystic fibrosis.
AB  - Malfunction of the cell surface glycoprotein, cystic fibrosis transmembrane
      conductance regulator, is the molecular hallmark of cystic fibrosis (CF), causing
      salt imbalance across the lung epithelium and biochemical and biophysical
      alterations of the mucous secretion and airway surfaces. Abnormal glycosylation
      of both secreted and membrane-tethered airway mucins in CF hosts are reported by
      a substantial body of literature and correlates with bacterial infection and
      inflammation in CF airways, features that are linked to the CF pathology. It is
      established that Pseudomonas aeruginosa and other CF-typic bacteria use the
      altered host mucin glycosylation as receptors for adhesion by dedicated lectins
      and adhesins recognizing an array of the aberrantly expressed glycan
      determinants. This review aims to describe the aberrant mucin glycosylation
      phenotype observed in CF airways relative to the non-CF equivalent by summarizing
      the wealth of literature on this topic. The possible causes and effects of
      altered glycosylation in the respiratory system are discussed. Specific attention
      is given to the adhesion mechanisms of the opportunistic P. aeruginosa, which
      utilizes the molecular alterations of the lung to gain access to the normally
      sterile airways. Finally, the emerging glycosylation-based therapeutics that show
      promising potential for reducing bacterial infection in individuals with CF by
      molecular mimicry mechanisms are discussed. 

PMID- 24138698
TI  - Triphos iridium(III) halide complex photochemistry: triphos arm dissociation.
AB  - Photolysis of Ir(triphos)X3 (triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane;
      X = Cl, Br) yields an insoluble product believed to be oligomeric
      [Ir(triphos)X3]n with bridging triphos and halide ligands. Refluxing pyridine
      (py) dissolves the insoluble photoproducts ultimately yielding the dangling
      triphos complexes mer-Ir(kappa(2)-triphos)(py)X3. Oxidation of the P center of
      the dangling arm of Ir(kappa(2)-triphos)(py)Cl3 yields mer-Ir(kappa(2)-P,P
      triphosO)(py)Cl3 (triphosO = MeC(CH2P(O)Ph2)(CH2PPh2)2), which was characterized
      by single-crystal X-ray diffraction. mer-Ir(kappa(2)-triphos)(py)Cl3 is also
      formed when Ir(triphos)Cl3 is photolyzed in the presence of py (phi = 26%). Both
      mer-Ir(kappa(2)-triphos)(py)Cl3 and mer-Ir(kappa(2)-P,P-triphosO)(py)Cl3
      photoisomerize in pyridine to their thermally unstable fac-isomers. Density
      functional theory (DFT) and time-dependent DFT (TDDFT) calculations suggest
      triphos ligand arm dissociation occurs along a triplet pathway from an initial
      Franck-Condon ligand-field excited state that relaxes to a Jahn-Teller axially
      distorted octahedral triplet with a long Ir-P bond. Subsequent triphos arm
      dissociation yields a distorted trigonal-bipyramidal triplet that undergoes
      intersystem crossing to a square pyramidal singlet. 

PMID- 24138699
TI  - A randomised trial of point-of-care tests for chlamydia and gonorrhoea infections
      in remote Aboriginal communities: Test, Treat ANd GO- the "TTANGO" trial
      protocol.
AB  - BACKGROUND: High prevalence rates of Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) have been reported in Aboriginal people in remote and regional
      areas of Australia for well over two decades, and repeat positivity rates are
      high. To interrupt disease transmission and reduce the risk of complications,
      early diagnosis and treatment is important. However in many remote and regional
      areas there are long delays between testing for these curable sexually
      transmissible infections and providing treatment, due to both physical distance
      from laboratories and difficulties when recalling patients for subsequent
      management once results are available. Point-of-care (POC) tests have the
      potential to provide more timely diagnosis, to increase treatment and contact
      tracing, and in turn reduce CT and NG infection rates. METHODS/DESIGN: TTANGO
      (Test, Treat, ANd GO) is a cross-over cluster randomised controlled trial in 12
      regional or remote Australian health services, which predominantly provide
      clinical services to Aboriginal people. The overall aim of TTANGO is to measure
      the clinical effectiveness, cost-effectiveness and cultural and operational
      acceptability of molecular POC testing for CT and NG infection. The primary
      outcome is repeat positivity at three months after treatment of an initial CT or
      NG infection. Participating health services will undertake the clinical
      management of CT and NG under two different modalities for one year each. In the
      first year, six health services will be randomly assigned to manage these
      infections under current diagnostic guidelines. The other six will supplement
      current diagnostic guidelines with POC testing, whereby diagnosis is made and
      subsequent treatment for those with positive POC tests is offered at the initial
      consultation. In the second year, the health services will cross over to the
      opposite management modality. TTANGO will be conducted over four years; 1.5 years
      of trial initiation and community consultation, 2 years of trial conditions and
      evaluation, and 6 months of data analysis and feedback. DISCUSSION: TTANGO is the
      first cluster randomised trial of POC testing for CT and NG internationally. The
      results of this trial will provide crucial information to guide sexual health
      clinical practice in remote Aboriginal communities and other high prevalence
      settings. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12613000808741.

PMID- 24138700
TI  - Malignant extra-adrenal pancreatic paraganglioma: case report and literature
      review.
AB  - BACKGROUND: Pancreatic paragangliomas are rare tumors, with only 16 reported
      cases to date. One of these cases demonstrates metastasis to lymph node, while
      another case was functional, however, none of these cases showed malignant and
      large, pancreatic paraganglioma with marked invasion. Also another unique feature
      was the age of our patient compared to the average reported ages in published
      literature (42-85 years). CASE PRESENTATION: A 19-year-old woman presented with a
      one-year history of intermittent abdominal pain. Physical examination showed a
      palpable mass in the right upper abdomen, but initial laboratory results were
      within normal ranges; tumor markers (CEA, AFP, and CA19-9) were negative. An
      abdominal and pelvic computed tomography (CT) scan showed a well-defined
      retroperitoneal para-aortic mass. The CT scan revealed that the surrounding lymph
      nodes were not enlarged, but the liver showed evidence of parenchymal
      infiltration. Intraoperatively, a large, firm tumor originating from the head of
      pancreas was found pushing on the caudate hepatic lobe and the inferior vena cava
      (IVC). The tumor was resected through a pancreaticoduodenectomy, involving
      segment VI of the liver and a small segment of the IVC. The blood pressure spiked
      (>220 mm Hg) when the tumor was manipulated during the operation. The final
      pathology report showed a 9-cm tumor with lymphovascular invasions;
      immunohistochemistry was positive for synaptophysin and chromogranin. All
      resection margins were negative and 1/15 lymph nodes was positive for metastasis.
      Post-operative recovery was unremarkable. One month after discharge, the patient
      was re-admitted with abdominal pain and found to have an abdominal collection at
      the resection site, which was drained under CT guidance. She received a
      therapeutic dose of I131-metaiodobenzylguanidine (MIBG). Follow-ups showed the
      absence of recurrence, and she has remained disease free. CONCLUSION: This
      patient was an extraordinary example of a rare tumor. Even more remarkable was
      that the tumor was malignant with lymph node invasion. To our knowledge, a case
      similar to that presented here has not been previously reported in the
      literature.

PMID- 24138701
TI  - Flow cytometry-assisted mix-and-read assay for ultrasensitive detection of
      protein kinase activity by use of Zr(4+)-functionalized mesoporous SiO2
      microspheres.
AB  - A flow cytometry-assisted mix-and-read assay is developed for ultrasensitive
      detection of protein kinase activity by use of Zr(4+)-functionalized mesoporous
      SiO2 microspheres (ZrMMs). This strategy integrates the distinct advantages of
      ZrMMs for highly specific recognition as well as high capacity binding of kinase
      induced fluorescent phosphopeptides and flow cytometry for powerful and
      separation-free bead analysis, leading to an ultrahigh sensitivity for kinase
      analysis in a extremely simple mix-and-read manner. Furthermore, this
      ultrasensitive design is well suitable for detection of cell kinase activities in
      complex biological samples and for screening of potential protein kinase
      inhibitors, which is of great significance for the development of targeted
      therapy, clinical diagnosis, and studies of cellular signal transduction
      pathways. 

PMID- 24138702
TI  - Transcriptional regulation of enniatins production by Fusarium avenaceum.
AB  - AIMS: The aim of this study was to analyse the transcriptional regulation of
      enniatins (ENs) production in Fusarium avenaceum. METHODS AND RESULTS: We develop
      a new method to quantify ENs in FDM agar medium. We performed an LC/MS/MS
      analysis to evaluate enniatin A, A1, B, B1 and B4 production by seven F.
      avenaceum strains and, in a time-course experiment, by ITEM 3404 to analyse the
      transcriptional regulation of the esyn1 gene. The expression profile, achieved by
      Real time reverse transcriptase assay, showed an activation of gene transcription
      at the seventh day of incubation, corresponding to the higher increase of total
      ENs production. Enniatin B was the most abundant ENs analogues, representing the
      90% of total ENs. The relative percentage of ENs remained unaltered during the
      experiment. CONCLUSIONS: We reported a transcriptional regulation of esyn1
      responsible for the modulation of ENs biosynthesis. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Enniatins are cyclic depsipeptides metabolites with a wide range of
      biological activities. They are also widespread contaminants in grains and
      cereals due to infection by enniatin-producing Fusarium species. This is the
      first article describing the transcriptional regulation of esyn1 gene that
      modulates ENs production in Fusarium avenaceum and provides new knowledge about
      the molecular mechanism underlying the biosynthesis of these important fungal
      metabolites in this toxigenic fungal species.

PMID- 24138704
TI  - Experimental research on intraocular aqueous flow by PIV method.
AB  - BACKGROUND: Aqueous humor flows regularly from posterior chamber to anterior
      chamber, and this flow much involves intraocular pressure, the eye tissue
      nutrition and metabolism. PURPOSE: To visualize and measure the intraocular flow
      regular pattern of aqueous humor. METHOD: Intraocular flow in the vitro eyeball
      is driven to simulate the physiological aqueous humor flow, and the flow field is
      measured by Particle Image Velocimetry(PIV). Fluorescent particle solution of a
      certain concentration was infused into the root of Posterior Chamber(PC) of vitro
      rabbit eye to simulate the generation of aqueous and was drained out at a certain
      hydrostatic pressure from the angle of Anterior Chamber(AC) to represent the
      drainage of aqueous. PIV method was used to record and calculate the flow on the
      midsagittal plane of the eyeball. RESULTS: Velocity vector distribution in AC has
      been obtained, and the distribution shows symmetry feature to some extent.
      Fluorescent particle solution first fills the PC as it is continuously infused,
      then surges into AC through the pupil, flows upwards toward the central cornea,
      reflecting and scattering, and eventually converges along the inner cornea
      surface towards the outflow points at the periphery of the eyeball. Velocity
      values around the pupillary margin are within the range of 0.008-0.012 m/s, which
      are close to theoretical values of 0.0133 m/s, under the driving rate of 100
      MUl/min. CONCLUSIONS: Flow field of aqueous humor can be measured by PIV method,
      which makes it possible to study the aqueous humor dynamics by experimental
      method. Our study provides a basis for experimental research on aqueous humor
      flow; further, it possibly helps to diagnose and treat eye diseases as shear
      force damage of ocular tissues and destructions on corneal endothelial cells from
      the point of intraocular flow field.

PMID- 24138703
TI  - Prevalence and correlates of depression among Australian women: a systematic
      literature review, January 1999- January 2010.
AB  - BACKGROUND: Little is known about the prevalence and correlates of depression
      among Australian women. This systematic review of depression among women in
      Australia, the largest identified to date, highlights the prevalence and
      correlates of depression across the life span. RESULTS: The report adhered to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA
      Statement (PRISMA). Six health related databases were selected: Medline,
      PsychInfo, SCOPUS, Cinhal, Informit and Cochrane Systematic Reviews. 1,888
      initial articles were found, and 111 articles were considered relevant for
      review. Prevalence rates of depression among women ranged from 2.6% to 43.9%.
      Higher rates were reported for younger women, or specific population groups. Most
      significant correlates included, age, adverse life events, tobacco use, sole
      motherhood, and previous mental health problems. CONCLUSIONS: Limitations include
      the scope of the investigation's aims and inclusion criteria, and the failure to
      identify gender specific data in most studies. Publication bias was likely, given
      that only papers reported (or translated) in English were included. Despite the
      breadth of information available, there were noticeable gaps in the literature.
      Some studies reported on affective disorders, but did not specifically report on
      depression; it is concluded that each mental illness warrants separate
      investigation. It was also common for studies to report a total prevalence rate
      without separating gender. This report recommends that it is vital to separate
      male and female data. The report concludes that more research is needed among mid
      age women, Indigenous women, non-heterosexual women and Culturally and
      Linguistically Diverse (CALD) women.

PMID- 24138705
TI  - Aphanamenes A and B, two new acyclic diterpene [4 + 2]-cycloaddition adducts from
      Aphanamixis grandifolia.
AB  - Aphanamenes A (1) and B (2), two unprecedented acyclic diterpene dimers formed
      via a [4 + 2]-cycloaddition, were isolated from the root bark of Aphanamixis
      grandifolia. Their structures were elucidated by spectroscopic analyses, and the
      absolute configuration of 1 was determined by ECD calculations. Both 1 and 2
      showed significant inhibition on NO production on lipopolysaccharide-induced
      RAW264.7 macrophages. 

PMID- 24138706
TI  - The association among leukocyte apoptosis, autoantibodies and disease severity in
      systemic lupus erythematosus.
AB  - BACKGROUND: Both apoptosis and autoantibodies are important factors associated
      with disease activity in the pathogenesis of systemic lupus erythematosus (SLE).
      This study tested the hypothesis that increased leukocyte apoptosis is associated
      with elevated levels of autoantibodies and the disease activity of SLE. METHODS:
      Leukocyte apoptosis was determined by flow cytometry, including annexin V,
      APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23
      patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with
      Sjogren's syndrome (SJS) and in 20 volunteer subjects. Titers of common
      autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients
      were also determined. RESULTS: Except for annexin V and APO 2.7 of monocytes and
      late apoptosis (annexin V+7-ADD) of lymphocytes, apoptosis in the total and in
      subsets of leukocytes were significantly higher in SLE patients than in controls
      (all p<0.05, post hoc analysis). The mean percentage of late apoptosis of
      leukocytes (annexin V+7-AAD) positively correlated with levels of anti-Ro52/60
      (r=0.513, p<0.01), anti-La (r=0.439, p=0.04), and anti-Mi-2 (r=0.492, p=0.02),
      and inversely correlated with both C3 and C4 levels, although not statistically
      significant. The percentage of APO2.7 of CD19+ cells positively correlated with
      SLEDAI-2 K score (p=0.01). CONCLUSIONS: Leukocyte apoptosis is significantly
      higher in patients with SLE and correlates well with the levels of several
      autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates
      with the disease activity of SLE.

PMID- 24138707
TI  - Direct and long-lasting effects elicited by repeated drug administration on 50
      kHz ultrasonic vocalizations are regulated differently: implications for the
      study of the affective properties of drugs of abuse.
AB  - Several studies suggest that 50-kHz ultrasonic vocalizations (USVs) may indicate
      a positive affective state in rats, and these vocalizations are increasingly
      being used to investigate the properties of psychoactive drugs. Previous studies,
      however, have focused on dopaminergic psychostimulants and morphine, whereas
      little is known about how other drugs modulate 50-kHz USVs. To further elucidate
      the neuropharmacology of 50-kHz USVs, the present study characterized the direct
      and long-lasting effects of different drugs of abuse, by measuring the number of
      50-kHz USVs and their 'trill' subtype emitted by adult male rats. Rats received
      repeated administrations of amphetamine (2 mg/kg, i.p.), 3,4
      methylenedioxymethamphetamine (MDMA, 7.5 mg/kg, i.p.), morphine (7.5 mg/kg,
      s.c.), or nicotine (0.4 mg/kg, s.c.), on either consecutive or alternate days
      (five administrations in total) in a novel environment. Seven days later, rats
      were re-exposed to the drug-paired environment, subjected to USVs recording, and
      then challenged with the same drug. Finally, 7 d after the challenge, rats were
      repeatedly exposed to the drug-paired environment and vocalizations were
      measured. Amphetamine was the only drug to stimulate 50-kHz USVs and 'trill'
      subtype emission during administration and challenge. Conversely, all rats
      emitted 50-kHz USVs when re-exposed to the test cage, and this effect was most
      marked in morphine-treated rats, and less evident in nicotine-treated rats. This
      study demonstrates that the direct and long-lasting effects of drugs on 50-kHz
      USVs are regulated differently, providing a better understanding of the
      usefulness of these vocalizations in the study of psychoactive drugs.

PMID- 24138708
TI  - Lower doses of isoflurane treatment has no beneficial effects in a rat model of
      intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage is a subtype of stroke that has a poor
      prognosis without an adequate therapy. Recently, the use of anesthetics such as
      isoflurane has been shown to be protective after cerebral ischemia. However, the
      potential therapeutic effect of isoflurane after intracerebral hemorrhage (ICH)
      has not been fully explored. RESULTS: In this study, male Sprague-Dawley rats
      (SD) were subjected to ICH and randomized into controls and 1.2% or 1.5%
      isoflurane posttreatment groups. Brain water content, neurological outcomes and
      matrix metalloproteinase-2 and -9 (MMP2-MMP9) plasma levels were quantified at 24
      hours. Isoflurane treatment did not reduce brain edema compared with controls in
      any of the applied isoflurane concentrations. Moreover, consistent with this lack
      of effect on brain edema, isoflurane posttreatment did not affect neurological
      outcomes in any of the tests used. Plasma MMP levels did not change. CONCLUSION:
      Our data suggested that there is no neuroprotection after isoflurane
      posttreatment in a rat model of ICH.

PMID- 24138709
TI  - Antisense-mediated post-transcriptional silencing of SCN1B gene modulates sodium
      channel functional expression.
AB  - BACKGROUND INFORMATION: Voltage-dependent sodium channels are membrane proteins
      essential for cell excitability. They are composed by a pore-forming alpha
      subunit and one or more beta subunits. Nine alpha subunit and five beta subunit
      isoforms have been identified in mammals: beta1, its splice variant beta1B,
      beta2, beta3 and beta4. Although they do not form the ion channel pore, beta
      subunits modulate both function as well as expression of sodium channels on cell
      membrane. RESULTS: To investigate the role of beta1 subunit on the modulation of
      sodium channel expression, we silenced this auxiliary subunit with specific
      antisense oligonucleotides (ASONs) in two rat cell lines, the GH3 and the H9C2,
      from neuro-ectoderm and cardiac myocyte origin, respectively. Treatment of cells
      with ASONs determined a reduction of about 50% of beta1 subunit mRNA and protein
      expression in both cell lines. We found that this level of beta1 subunit
      silencing resulted in an overall decrease of alpha subunit mRNA, protein
      expression and a decrease of sodium current density, without altering
      significantly the voltage-dependent and kinetic properties of the currents. In
      GH3 cells, the beta1 subunit silencing reduced the expression of Nav1.1, Nav1.3
      and Nav1.6 isoforms, whereas the Nav 1.2 isoform expression remained unaltered.
      The expression of the only alpha subunit present in H9C2 cells, the Nav1.5, was
      also reduced by beta1 subunit silencing. CONCLUSIONS: These results indicate that
      the beta1 subunit may exert an isoform-specific fine-tuned modulation of sodium
      channel expression.

PMID- 24138710
TI  - The OPERA trial - comparison of early nasal high flow oxygen therapy with
      standard care for prevention of postoperative hypoxemia after abdominal surgery:
      study protocol for a multicenter randomized controlled trial.
AB  - BACKGROUND: Respiratory support following postoperative extubation is of major
      importance to prevent hypoxemia and subsequent respiratory failure and
      reintubation. High-flow nasal cannula oxygen (HFNC) delivers a flow-dependent
      positive airway pressure and improves oxygenation by increasing end-expiratory
      lung volume. Whether application of HFNC may have therapeutic advantages over
      conventional oxygen therapy for respiratory support in the early postextubation
      surgical period remains to be established. METHODS/DESIGN: The Optiflow for
      prevention of post-extubation hypoxemia after abdominal surgery (OPERA) trial is
      an investigator-initiated multicenter randomized controlled two-arm trial with
      assessor-blinded outcome assessment, randomizing 220 patients with intermediate
      to high risk of pulmonary complications after abdominal surgery to receive HFNC
      or conventional oxygen therapy following extubation, stratified by the presence
      of epidural analgesia and center. The primary outcome measure is the percentage
      of patients with postoperative hypoxemia one hour after tracheal extubation.
      Secondary outcome measures are postoperative pulmonary complications, need for
      noninvasive ventilation and intubation for respiratory failure. DISCUSSION: The
      OPERA trial is the first randomized controlled study powered to investigate
      whether early application of HFNC following extubation after abdominal surgery
      prevents against postoperative hypoxemia and pulmonary complications. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01887015.

PMID- 24138711
TI  - A modified preparation procedure for carbon nanotube-confined Nd/Na
      heterobimetallic catalyst for anti-selective catalytic asymmetric nitroaldol
      reactions.
AB  - A recyclable asymmetric metal-based catalyst is a rare entity among the vast
      collection of asymmetric catalysts developed so far. Recently we found that the
      combination of a self-assembling metal-based asymmetric catalyst and multiwalled
      carbon nanotubes (MWNTs) produced a highly active and recyclable catalyst in
      which the catalytically active metal complex was dispersed in the MWNT network.
      Herein we describe an improved preparation procedure and full details of a Nd/Na
      heterobimetallic complex confined in MWNTs. Facilitated self-assembly of the
      catalyst with MWNTs avoided the sacrificial use of excess chiral ligand for the
      formation of the heterobimetallic complex, improving the loading ratio of the
      catalyst components. Eighty-five percent of the catalyst components were
      incorporated onto MWNTs to produce the confined catalyst, which was a highly
      efficient and recyclable catalyst for the anti-selective asymmetric nitroaldol
      reaction. The requisite precautions for the catalyst preparation to elicit
      reproducible catalytic performance are summarized. Superior catalytic profiles
      over the prototype catalyst without MWNTs were revealed in the synthesis of
      optically active 1,2-nitroalkanols, which are key intermediates for the synthesis
      of therapeutics. 

PMID- 24138712
TI  - Chronic paroxetine treatment: effects on other non-serotonergic neurotransmitter
      systems.
AB  - Due to its efficacy and acceptability, paroxetine is situated in the top ten of
      drugs prescribed for the treatment of major depression and essentially all
      anxiety disorders. Adults under paroxetine treatment report relief after 4-6
      weeks of administration; furthermore, this drug can be prescribed for periods
      lasting longer than one year. Therefore, paroxetine treatment has a pattern of
      ingestion that is mainly chronic rather than acute. There is a considerable
      number of reviews in the literature concerning the effects of paroxetine on the
      serotonergic system; however, the alterations caused by chronic ingestion of this
      drug in other neurotransmitter systems have received little attention. For this
      reason, we consider very important to review the experimental studies concerning
      the effects of chronic paroxetine intake on neurotransmitter levels, neuronal
      firing rate and the expression of receptors and transporters in different
      neurotransmitter systems in the brain. According to the experimental data
      analyzed in this work, we can establish that long-term paroxetine intake has the
      ability to increase GABA, glutamate, dopamine and noradrenaline levels in the
      brain. Furthermore, high levels of AMPA, orexine-1,2 and histamine-1 receptors
      have been reported in different brain regions after treatment with paroxetine
      over several weeks. In addition, paroxetine has differential effects on
      neuropeptide systems, such as galanine, opioid receptors and substance P.
      Available data lead us to establish that chronic ingestion of paroxetine induces
      changes in several neurotransmitters and neuropeptides, thus illuminating how
      each one may contribute to the antidepressant and anxiolytic response elicited by
      this drug. We consider that all reported changes in the neurotransmitter systems
      should be further considered to individualize clinical treatment and, in the case
      of patients taking a drug "cocktail", to gain better control over drug
      interactions and adverse effects. 

PMID- 24138713
TI  - Irreversible EGFR inhibitors in the treatment of advanced NSCLC.
AB  - The epidermal growth factor receptor (EGFR) is among the most important targets
      in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and
      gefitinib, two small molecules, are reversible EGFR tyrosine kinase inhibitors
      (TKIs). Non-small cell lung cancers with EGFR mutations, are characterized by
      excellent responses when treated with the EGFR-TKIs gefitinib and erlotinib.
      However, all the patients with tumors harbouring EGFR mutations experience
      disease progression after a median of 10 to 14 months of treatment with gefitinib
      or erlotinib. A group of new generation EGFR-TKIs irreversibly inhibit EGFR-TK
      and represent one of the strategies that may potentially overcome the acquired
      resistance to gefitinib and erlotinib or achieve better outcomes than reversible
      inhibitors in the first-line treatment of EGFR mutant lung cancers. Afatinib
      (BIBW 2992) and PF299804 are the irreversible EGFR-TKIs with the most relevant
      data in the treatment of advanced NSCLC, as primary EGFR-targeted therapy and
      after resistance to reversible EGFR-TKIs. However, to date, the role of
      irreversible EGFR inhibitors remains to be defined.

PMID- 24138714
TI  - Signaling intermediates (MAPK and PI3K) as therapeutic targets in NSCLC.
AB  - The RAS/RAF/MEK/ ERK and the PI3K/AKT/mTOR pathways govern fundamental
      physiological processes, such as cell proliferation, differentiation, metabolism,
      cytoskeleton reorganization and cell death and survival. Constitutive activation
      of these signal transduction pathways is a required hallmark of cancer and
      dysregulation, on either genetic or epigenetic grounds, of these pathways has
      been implicated in the initiation, progression and metastastic spread of lung
      cances. Targeting components of the MAPK and PI3K cascades is thus an attractive
      strategy in the development of novel therapeutic approaches to treat lung cancer,
      although the use of single pathway inhibitors has met with limited clinical
      success so far. Indeed, the presence of intra- and inter-pathway compensatory
      loops that re-activate the very same cascade, either upstream or downstream the
      point of pharmacological blockade, or activate the alternate pathway following
      the blockade of one signaling cascade has been demonstrated, potentially driving
      preclinical (and possibly clinical) resistance. Therefore, the blockade of both
      pathways with combinations of signaling inhibitors might result in a more
      efficient anti-tumor effect, and thus potentially overcome and/or delay clinical
      resistance, as compared with single agent. The current review aims at summarizing
      the current status of preclinical and clinical research with regard to pathway
      crosstalks between the MAPK and PI3K cascades in NSCLC and the rationale for
      combined therapeutic pathway targeting. 

PMID- 24138715
TI  - Across the universe of K-RAS mutations in non-small-cell-lung cancer.
AB  - RAS family proteins are important signaling molecules that regulate cell growth,
      survival and differentiation by coupling receptor activation to downstream
      effector pathways. Three distinct genes encode for the three different proteins H
      , K-, and N- RAS. These proteins share high sequence homology, particularly at
      the N-Terminal domain. Among them, K-RAS is one of the most frequently mutated in
      human cancer. The majority of the mutations present in K-RAS are at codon 12
      (from 80 to 100%) followed by codon 13 and 61. In all cases, aminoacid change
      leads to a constitutively activated protein. K-RAS mutations have a role in tumor
      development as well as in tumor progression and resistance. Despite the various
      studies which have been published, the prognostic and predictive role of K-RAS
      mutations is still under debate. Keeping in mind that the glycine present at
      position 12 can be substituted by valine, aspartic acid or cysteine, it could be
      well understood that each different substitution plays a different role in K-RAS
      dependent processes. The present article focuses on the molecular and biological
      characteristics of K-RAS protein, its role in NSCLC tumor development and
      progression. We also present an overview of the preclinical models both in vitro
      and in vivo available to determine the role of K-RAS in tumor progression and
      response to treatment and on the recent results obtained in this field. Finally,
      we have considered the impact of KRAS mutations in clinical practice, analyzing
      the different recent trials that have taken into consideration K-RAS. 

PMID- 24138716
TI  - MET and ALK as targets for the treatment of NSCLC.
AB  - Cell proliferation, survival, differentiation, migration and metabolism are some
      of the fundamental cellular processes tightly controlled by the activity of
      tyrosine-kinase receptors (RTKs). The aberrant signaling of RTKs contributes to
      cancer growth and survival and has become important target for therapeutic
      approaches. Well-characterized kinase molecular target in lung cancer, in
      particular in non-small cell lung cancer (NSCLC), is the activated epidermal
      growth factor receptor (EGFR) pathway. More recently, the oncogenic role of other
      two tyrosine-kinases, the hepatocyte growth factor receptor (MET) and the
      anaplastic lymphoma kinase (ALK), has been recognized. Many different therapeutic
      strategies have been investigated with the goal to inhibit these receptors,
      subsequent downstream signaling cascades and arrest tumor growth. This review
      will discuss the MET and ALK pathways, the different strategies of their
      inhibition and the potential approaches to overcome acquired resistance to kinase
      inhibitors in these two genes. 

PMID- 24138717
TI  - Approaching the increasing complexity of non-small cell lung cancer taxonomy.
AB  - The advent of molecular targeted agents is changing the treatment of solid
      tumors. In non-small-cell lung cancer, compounds directed against oncogenic
      proteins offer novel therapeutic opportunities for a fraction of patients whose
      tumors harbor specific genetic defects. With the increased level of resolution
      achieved by high-throughput technologies, the taxonomy of lung cancer is rapidly
      changing. For instance, by cataloguing genetic abnormalities in squamous cell
      lung cancer the Cancer Genome Atlas Network revealed the existence of multiple
      molecular entities, each one characterized by specific molecular abnormalities,
      and by a different spectrum of activated/ inactivated molecular networks.
      Although this increased complexity could be perceived as a further drawback in
      effective anticancer therapy, on the other hand the combined interrogation of
      genomic and proteomic data is expected to provide the whole molecular map of each
      tumor, and to determine the information flow in the explored biological system.
      In particular, novel genetic and proteomic approaches are offering the
      opportunity for matching specific genetic defects and aberrant protein-protein
      interactions with active pathway-targeted inhibitors. Moreover, the isolation and
      characterization of a cellular pool endowed with stem-like traits, and able to
      recapitulate the parental disease in animals, is enabling investigators to
      recreate the individual patient tumor in the laboratory. In this article, we
      discuss how novel technologies and cellular and animal models, applied to lung
      cancer research, hold the potential to foster a new wave of biomarker-driven
      clinical trials.

PMID- 24138718
TI  - Signaling pathways modulating dependence of lung cancer on mutant epidermal
      growth factor receptor and mechanisms of intrinsic and acquired resistance to
      tyrosine kinase inhibitors.
AB  - A new era in lung cancer targeted therapy arrived with the discovery of a subset
      of lung adenocarcinomas harboring activating mutations of the epidermal growth
      factor receptor (EGFR), whose tyrosine kinase activity can be selectively blocked
      by small molecule pharmaceuticals referred as tyrosine kinase inhibitors (TKIs).
      This was the starting point for a less toxic and more effective treatment
      strategy for a disease that has historically presented as chemorefractory and
      highly lethal. In spite of this progress, only 80% of the patients treated with
      this class of compounds will obtain a clinical benefit, of variable magnitude and
      duration, with remaining patients being primarily refractory to the treatment.
      Moreover, responding tumors will eventually develop acquired resistance to TKIs
      and progress to more advanced stages. In this review we summarize the current
      knowledge with regard to the mechanisms leading to tumor regression and the
      modifiers of this primary response that determine significant variability in
      sensitivity of tumors harboring EGFR activating mutations, ranging from complete
      remission to primary refractoriness. We also analyze the mechanisms of secondary
      resistance and the strategies the scientific community is exploring in order to
      overcome these barriers. 

PMID- 24138719
TI  - Anti-angiogenic drugs and biomarkers in non-small-cell lung cancer: a 'hard days
      night'.
AB  - The discovery of specific molecular alterations (i.e. EGFR activating mutations,
      EML4/ALK translocation, ROS1 rearrangements) in a selected population of patients
      affected by non small cell lung cancer (NSCLC) translated into effective
      treatments for this small but well defined fraction of patients, driven by the
      use of predictive biomarkers of efficacy for targeted agents. Unfortunately, the
      same reliable predictive biomarkers are lacking for anti-angiogenic drugs.
      Angiogenesis plays a major role in the progression of NSCLC, however, anti
      angiogenic agents provided a minimal, although significant, clinical benefit in
      unselected populations, burdened by a not negligible toxicities. In this context,
      no validated angiogenic factor or other molecular biomarker of angiogenesis can
      reliably predict clinical outcome, sensitivity, early response or resistance to
      any of the investigated anti-angiogenic therapies currently used. Moreover, the
      available clinical data are prevalently retrospective, underpowered, and, in many
      cases, contradictory, thus underscoring that the understanding of the complex
      architecture of angiogenic signaling is still incomplete. We here review the
      currently available studies on the effect of anti-angiogenic drugs in NSCLC, with
      a particular focus on bio-molecular factors that are regarded as potential
      predictors of treatment efficacy. 

PMID- 24138720
TI  - Pharmacogenetics of non-small cell lung cancer (NSCLC): time to "work it out"?
AB  - The disappointing results in long-term survival of patients affected by non-small
      cell lung cancer (NSCLC) may be attributed, at least in part, to the lack of
      knowledge on the way by which genetic characteristics in normal and neoplastic
      cells affect responsiveness as well as metabolism of chemotherapy and new
      targeted agents. This issue deserves further pharmacogenetics studies, in order
      to identify patients who are most likely to benefit from specific therapies
      selected on the base of the individual and tumor genetic features, thus improving
      the efficacy/toxicity profile of the treatment strategy. Even if most meta
      analyses in NSCLC yielded contradictory results, a number of candidate biomarkers
      for response/resistance to conventional chemotherapeutic agents such as
      gemcitabine, platinum-compounds, pemetrexed and taxanes have been proposed.
      Similarly, recent studies suggested the key role of polymorphisms in the
      prediction of toxicity to EGFR-targeted agents. However, larger prospective
      randomized trials of personalized therapy to validate these biomarkers are still
      needed. The unification of the technical procedures, as well as additional
      investigation to unravel pivotal factors influencing genotype-phenotype
      relationships, represent other crucial issues. From this perspective, functional
      studies aiming at unravel eventual pharmacokinetics/pharmacodynamics interactions
      are critical for the pharmacogenetic optimization of anti-cancer regimens. With
      the development of high-throughput technologies, including whole exome analyses,
      the traditional pharmacogenetic approach that till present has relied only on
      candidate genes suspected of influencing drug response/metabolism can be
      fulfilled with further lists of potential predictive alleles. The clinical
      implementation of such pharmacogenetics/genomics studies as well as of
      therapeutic drug monitoring could enable clinicians to personalize treatment to
      enhance efficacy and/or limit toxicity.

PMID- 24138721
TI  - MicroRNAs in non-small cell lung cancer: current status and future therapeutic
      promises.
AB  - A biological characterization of tumor tissue is mandatory in NSCLC patients to
      identify cases at high risk of recurrence and to drive current targeted therapies
      such as EGFR and ALK inhibitors. In addition, promising results have been
      reported on the utility of molecular parameters for the prediction of the
      efficacy of systemic cytotoxic therapy. MicroRNAs (miRNAs) are small single
      stranded non-coding RNA molecules, which regulate gene expression at the
      posttranscriptional level. Growing evidence suggests that miRNAs are expressed
      aberrantly in many human cancers and that they play a significant role in
      carcinogenesis and cancer progression. There is increasing evidence that miRNA
      profiling may become an accurate way to differentiate tumor subtypes, determine
      prognosis and response to therapy. This review aims to summarize the current
      literature on this rapidly evolving field. 

PMID- 24138722
TI  - Centrality in children's best friend networks: the role of social behaviour.
AB  - Centrality is an indicator of an individual's relative importance within a social
      group. Predictors of centrality in best friendship networks were examined in 146
      children (70 boys and 76 girls, Mage  = 9.95). Children completed measures of
      social confidence, social desirability, friendship quality, school liking, and
      loneliness and nominated their best friends from within their class at two time
      points, 3 months apart. Multigroup path analysis revealed gender differences in
      the antecedents of centrality. Social confidence, social desirability, and
      friendship quality predicted changes in the indicators of centrality in best
      friend networks over time. Boys' social behaviour positively predicted changes in
      centrality, whereas girls' social behaviour negatively predicted changes in
      centrality. Together, these findings suggest that some aspects of social
      behaviour are influential for centrality in best friend groups. 

PMID- 24138723
TI  - Anthelmintic efficacy of an oral formulation of Aurixazol against
      gastrointestinal nematodes of naturally and experimentally infected sheep.
AB  - As a result of the need to develop new active principles for the control of
      endoparasites in ruminants, the present in vivo study evaluated a formulation
      containing 24% Aurixazol (48 mg/kg), a parasiticide molecule based on
      disophenolate of levamisole. Two experiments were conducted: one evaluating the
      anthelmintic efficacy of 24% Aurixazol (48 mg/kg) against gastrointestinal
      nematodes in naturally infected sheep, compared to an association of ivermectin
      (0.2mg/kg)+albendazole (5.0mg/kg)+levamisole (7.5mg/kg) (IAL), and a second one
      which evaluated the persistent efficacy of the same formulation against immature
      stages (L4) and adults of Haemonchus contortus in experimentally infected
      animals. In experiment I, against H. contortus, the formulation of Aurixazol and
      the IAL association reached efficacies (arithmetic means) of 99.32% and 96.11%,
      respectively. For Trichostrongylus colubriformis, the efficacy values were 88.92%
      and 98.08% for Aurixazol and the IAL association, respectively. Both formulations
      were totally effective against Oesophagostomum columbianum (100%). The results of
      the statistical analysis demonstrated that the mean parasitic burden of treated
      animals was significantly different (P <= 0.05) compared to the average number of
      helminths diagnosed in animals from the control group for H. contortus, T.
      colubriformis and O. columbianum. Comparing only the treated groups, it was
      possible to verify that the average number of H. contortus recovered from animals
      treated with Aurixazol was different (P <= 0.05) when compared to the mean amount
      recovered from sheep treated with the IAL association. When evaluating the
      prevention of H. contortus infection in experiment II, Aurixazol did not present
      preventive efficacy. Up until 21 days after treatment the groups treated with
      Aurixazol contained less adults and L4 of H. contortus (P <= 0.05) when compared
      to the non-medicated control group. However, future studies will be necessary to
      assess the effectiveness of Aurixazol against nematode strains resistant to
      levamisole and disophenol, but the efficacy results described in this study allow
      to state that Aurixazol can, associated with other measures, become an important
      tool in the control of sheep nematodes.

PMID- 24138725
TI  - Fine needle biopsy with cytology in paediatrics: the importance of a
      multidisciplinary approach and the role of ancillary techniques.
AB  - Fine needle biopsy (FNB) with cytology has long been regarded as an excellent
      technique as the first choice for diagnosing adult tumours. Being an inexpensive
      minimally invasive technique with high accuracy and diagnostic immediacy through
      rapid on-site evaluation, it is also ideal for implementation in the paediatric
      setting, particularly in developing countries. Furthermore, it allows
      complementary and advanced procedures such as flow cytometry, polymerase chain
      reaction (PCR) or fluorescence in situ hybridization (FISH), among others, which
      enhances the diagnostic capacity of this technique and gives it a key role in
      risk stratification and therapeutic decision-making for several tumours. The
      advantages of FNB are optimized in the setting of a multidisciplinary team where
      cytologist, clinician and radiologist play leading roles. Paediatric tumours are
      rare and most ancillary techniques are cost-effective but complex to be
      implemented in small centres with limited experience in paediatric pathology.
      Therefore reference centres are essential, in order to establish teams with
      extensive experience and expertise. Hence, any child with a suspected malignancy
      should be directly referred to a paediatric oncology unit. Focusing on a
      practical approach to the assessment of paediatric lymphadenopathies and non
      central nervous system solid tumours we review the effectiveness of FNB as
      applied concurrently with ancillary techniques in a multidisciplinary approach to
      the diagnosis, prognosis and therapeutic decisions of paediatric tumours and
      tumour-like lesions. 

PMID- 24138724
TI  - An optimised protocol for molecular identification of Eimeria from chickens.
AB  - Molecular approaches supporting identification of Eimeria parasites infecting
      chickens have been available for more than 20 years, although they have largely
      failed to replace traditional measures such as microscopy and pathology.
      Limitations of microscopy-led diagnostics, including a requirement for specialist
      parasitological expertise and low sample throughput, are yet to be outweighed by
      the difficulties associated with accessing genomic DNA from environmental Eimeria
      samples. A key step towards the use of Eimeria species-specific PCR as a
      sensitive and reproducible discriminatory tool for use in the field is the
      production of a standardised protocol that includes sample collection and DNA
      template preparation, as well as primer selection from the numerous PCR assays
      now published. Such a protocol will facilitate development of valuable
      epidemiological datasets which may be easily compared between studies and
      laboratories. The outcome of an optimisation process undertaken in laboratories
      in India and the UK is described here, identifying four steps. First, samples
      were collected into a 2% (w/v) potassium dichromate solution. Second, oocysts
      were enriched by flotation in saturated saline. Third, genomic DNA was extracted
      using a QIAamp DNA Stool mini kit protocol including a mechanical homogenisation
      step. Finally, nested PCR was carried out using previously published primers
      targeting the internal transcribed spacer region 1 (ITS-1). Alternative methods
      tested included sample processing in the presence of faecal material, DNA
      extraction using a traditional phenol/chloroform protocol, the use of SCAR
      multiplex PCR (one tube and two tube versions) and speciation using the
      morphometric tool COCCIMORPH for the first time with field samples.

PMID- 24138726
TI  - Health care professionals' perspectives of living and dying with primary
      malignant glioma: Implications for a unique cancer trajectory.
AB  - OBJECTIVES: Health care professionals (HCPs) caring for people with primary
      malignant glioma (PMG) and their carers see many of the profound challenges
      facing this group, yet their perspectives are not documented. This study aimed to
      understand and document the unique perspective of HCPs in relation to the
      supportive and palliative care needs of patients with PMG and their carers, with
      a view to developing a model of care. METHODS: Qualitative study involving semi
      structured focus groups and interviews with 35 medical, nursing and allied health
      staff actively engaged in providing care for this patient group. Purposive and
      theoretical sampling from two major metropolitan hospitals and one community
      palliative care service in Australia was utilised to seek perspectives from a
      variety of disciplines and health care settings. Thematic analysis was conducted
      by three independent researchers, using a constant comparative method influenced
      by grounded theory. RESULTS: Key themes relating to the needs of people with PMG
      which were apparent from the HCPs included: The difference in the illness course
      of glioma compared to other cancers; Limitations of current medical care;
      Challenges in balancing hope with reality of the illness; and Recommendations to
      improve care, including recognising the role of family and moving from a model
      where services are offered in response to demonstrated needs. Significance of the
      results: Current models of care based upon the classic cancer trajectory are
      unresponsive to the needs of people with PMG. Care may be enhanced by moving
      towards a proactive approach, extending the goals of care beyond medical needs
      and broadening the focus of care to include family needs.

PMID- 24138727
TI  - Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic
      and cell polarity.
AB  - Microvillus inclusion disease (MVID) is a congenital enteropathy characterized by
      loss of apical microvilli and formation of cytoplasmic inclusions lined by
      microvilli in enterocytes. MVID is caused by mutations in the MYO5B gene, coding
      for the myosin Vb motor protein. Although myosin Vb is implicated in the
      organization of intracellular transport and cell surface polarity in epithelial
      cells, its precise role in the pathogenesis of MVID is unknown. We performed
      correlative immunohistochemistry analyses of sections from duodenal biopsies of a
      MVID patient, compound heterozygous for two novel MYO5B mutations, predicting
      loss of function of myosin Vb in duodenal enterocytes together with a stable
      MYO5B CaCo2 RNAi cell system. Our findings show that myosin Vb-deficient
      enterocytes display disruption of cell polarity as reflected by mislocalized
      apical and basolateral transporter proteins, altered distribution of certain
      endosomal/lysosomal constituents including Rab GTPases. Together, this severe
      disturbance of epithelial cell function could shed light on the pathology and
      symptoms of MVID. 

PMID- 24138728
TI  - Patients' perceptions of waiting for bariatric surgery: a qualitative study.
AB  - BACKGROUND: In Canada waiting lists for bariatric surgery are common, with wait
      times on average > 5 years. The meaning of waiting for bariatric surgery from the
      patients' perspective must be understood if health care providers are to act as
      facilitators in promoting satisfaction with care and quality care outcomes. The
      aims of this study were to explore patients' perceptions of waiting for bariatric
      surgery, the meaning and experience of waiting, the psychosocial and behavioral
      impact of waiting for treatment and identify health care provider and health
      system supportive measures that could potentially improve the waiting experience.
      METHODS: Twenty-one women and six men engaged in in-depth interviews that were
      digitally recorded, transcribed verbatim and analysed using a grounded theory
      approach to data collection and analysis between June 2011 and April 2012. The
      data were subjected to re-analysis to identify perceived health care provider and
      health system barriers to accessing bariatric surgery. RESULTS: Thematic analysis
      identified inequity as a barrier to accessing bariatric surgery. Three areas of
      perceived inequity were identified from participants' accounts: socioeconomic
      inequity, regional inequity, and inequity related to waitlist prioritization.
      Although excited about their acceptance as candidates for surgery, the waiting
      period was described as stressful, anxiety provoking, and frustrating. Anger was
      expressed towards the health care system for the long waiting times. Participants
      identified the importance of health care provider and health system supports
      during the waiting period. Recommendations on how to improve the waiting
      experience included periodic updates from the surgeon's office about their
      position on the wait list; a counselor who specializes in helping people going
      through this surgery, dietitian support and further information on what to expect
      after surgery, among others. CONCLUSION: Patients' perceptions of accessing and
      waiting for bariatric surgery are shaped by perceived and experienced
      socioeconomic, regional, and waitlist prioritization inequities. A system
      addressing these inequities must be developed. Waiting for surgery is inherent in
      publicly funded health care systems; however, ensuring equitable access to
      treatment should be a health system priority. Supports and resources are required
      to ensure the waiting experience is as positive as possible.

PMID- 24138729
TI  - Governing healthcare through performance measurement in Massachusetts and the
      Netherlands.
AB  - Massachusetts and the Netherlands have implemented comprehensive health reforms,
      which have heightened the importance of performance measurement. The performance
      measures addressing access to health care and patient experience are similar in
      the two jurisdictions, but measures of processes and outcomes of care differ
      considerably. In both jurisdictions, the use of health outcomes to compare the
      quality of health care organizations is limited, and specific information about
      costs is lacking. New legislation in both jurisdictions led to the establishment
      of public agencies to monitor the quality of care, similar mandates to make the
      performance of health care providers transparent, and to establish a shared
      responsibility of providers, consumers and insurers to improve the quality of
      health care. In Massachusetts a statewide mandatory quality measure set was
      established to monitor the quality of care. The Netherlands is stimulating
      development of performance measures by providers based on a mandatory framework
      for developing such measures. Both jurisdictions are expanding the use of patient
      reported outcomes to support patient care, quality improvement, and performance
      comparisons with the aim of explicitly linking performance to new payment
      incentives. 

PMID- 24138730
TI  - PFI redux? Assessing a new model for financing hospitals.
AB  - There is a growing need for investments in hospital facilities to improve the
      efficiency and quality of health services. In recent years, publicly financed
      hospital organisations in many countries have utilised private finance
      arrangements, variously called private finance initiatives (PFIs), public-private
      partnerships (PPPs) or P3s, to address their capital requirements. However, such
      projects have become more difficult to implement since the onset of the global
      financial crisis, which has led to a reduction in the supply of debt capital and
      an increase in its price. In December 2012, the government of the United Kingdom
      outlined a comprehensive set of reforms to the private finance model in order to
      revive this important source of capital for hospital investments. This article
      provides a critical assessment of the 'Private Finance 2' reforms, focusing on
      their likely impact on the supply and cost of capital. It concludes that
      constraints in supply are likely to continue, in part due to regulatory
      constraints facing both commercial banks and institutional investors, while the
      cost of capital is likely to increase, at least in the short term. 

PMID- 24138731
TI  - The recent health reform in Croatia: true reforms or just a fundraising exercise?
AB  - Croatia's most recent reform of the healthcare system was implemented in 2008.
      The aim of the reform was to enhance financial stability of the system by
      introducing additional sources of financing, as well as increase the efficiency
      of the system by reducing sick pay transfers to households, rationalising
      spending on pharmaceuticals, restructuring hospitals etc. This paper attempts to
      assess the success of the 2008 healthcare system reform in reaching financial
      stability and sustainability, and to evaluate the effects of the reform on equity
      in funding the system. It takes into account the fact that the reform coincided
      with a severe economic crisis and decline in the overall living standard of
      Croatian citizens. The paper shows that the reform ended up being expansionary
      and thus impaired the necessary fiscal adjustment. Finally, it is argued that in
      circumstances of declining disposable incomes, increased co-payments aimed at the
      financial stabilisation of the health system made health services less affordable
      and could have had detrimental effects on equity in the utilisation of health
      care.

PMID- 24138732
TI  - Expression of epidermal growth factor receptors and epidermal growth factor,
      amphiregulin and neuregulin in bovine uteroplacental tissues during gestation.
AB  - INTRODUCTION: Growth factors are proteins that bind to specific cell surface
      receptors that initiate signalling pathways and result in proliferation or
      differentiation of the affected cells. During gestation, epidermal growth factor
      receptors (ErbB1-4) and its ligands (epidermal growth factor-EGF, amphiregulin
      AREG, neuregulin1-NRG1) play a significant role in differentiation, function and
      growth of the uterus. OBJECTIVES: To determine the role of ErbB receptors and
      EGF, AREG and NRG1 in bovine uteroplacental tissues during gestation. METHODS:
      Placentomes and interplacentomal areas from 30 cows from early gestation until
      near term were analysed by immunohistochemistry. RESULTS: ErbB receptors and its
      ligands were observed in uteroplacental tissues and its expression was maintained
      throughout pregnancy, but ErbB1 receptor did not exist in the caruncular and
      cotyledonary stromal cells. Besides, caruncular stromal cells did not present
      with any immune reaction for EGF, AREG and NRG1. Generally, it was observed that
      total scores for ErbB receptors and its ligands (EGF, AREG and NRG1) had
      decreased from early to late gestation (p < 0.05). CONCLUSION: Our study shows
      the presence of ErbB receptors and its ligands participate in the mid- and late
      phases of pregnancy. To our knowledge, this is the first study on the expression
      of NRG1 during bovine pregnancy. These results indicates that these factors may
      play a crucial role not only to enable cellular proliferation and differentiation
      in the uterus throughout gestation, but also to have a potential role in the
      cellular communication maintained between the embryo/fetus and uterus by the
      placenta.

PMID- 24138733
TI  - Intraoperative use of CT imaging.
AB  - This article presents an overview of intraoperative computed tomography for
      maxillofacial reconstructive surgery. It reviews the current literature and
      offers guidelines and techniques for the use of intraoperative imaging. 

PMID- 24138734
TI  - Contemporary management of traumatic fractures of the frontal sinus.
AB  - This article discusses the classic and contemporary management strategies for
      treating frontal sinus fractures. The goals of management of frontal sinus
      fractures are to create a safe sinus by minimizing the likelihood of early and
      late complications while preserving the function of the sinus and maintaining the
      cosmetic appearance of the upper face. The assessment and classification of
      patients with frontal sinus injuries, their management, and the treatment of
      complications are reviewed. 

PMID- 24138735
TI  - Surgical treatment of traumatic injuries of the cranial base.
AB  - Skull-base fractures involve one or more of the cribriform plate of the ethmoid
      bone, orbital plate of the frontal bone, sphenoid bone, occipital bone, and
      petrous or temporal bone. Although the fractures themselves only require
      reduction and reconstruction when the skull base is severely comminuted and
      altered, even small fractures and the traumatic shear forces can create tears in
      the meninges and thus predispose to cerebrospinal fluid leaks. This article
      explores the preoperative, intraoperative, and postoperative management of skull
      base fractures, which most commonly involves resolution of the cerebrospinal
      fluid leak and the prevention of future leaks or meningoencephaloceles. 

PMID- 24138736
TI  - Surgical management of complex midfacial fractures.
AB  - This article presents an overview of surgical management for complex midfacial
      fractures for the practicing otolaryngologist-head and neck surgeon. Discussion
      includes the important anatomic relationships; pathophysiology; clinical
      features; pertinent physical examination findings; imaging; surgical approaches;
      and techniques for repair of zygomaticomaxillary complex, orbital, naso-orbital
      ethmoid, and Le Fort fractures. 

PMID- 24138737
TI  - Condylar fractures.
AB  - The purpose of this article is to review the basic indications for different
      treatments of condylar and subcondylar fractures. It also reviews the steps of
      different surgical approaches to access the surgical area and explains the pros
      and cons of each procedure. 

PMID- 24138738
TI  - Management of pediatric mandible fractures.
AB  - When determining the optimal treatment strategy for a pediatric mandible
      fracture, planning must factor in the patient's age, anatomy, stage of dental
      development, fracture site, and ability to cooperate with the proposed treatment
      plan. Careful consideration must be given to the possibility of long-term growth
      disturbance with various fracture locations and types of treatment. This article
      reviews the current principles of the management of pediatric mandibular
      fractures. 

PMID- 24138739
TI  - Dentoalveolar trauma.
AB  - Dentoalveolar injuries are an important and common component of
      craniomaxillofacial trauma. The dentition serves as a vertical buttress of the
      face and fractures to this area may result in malalignment of facial subunits.
      Furthermore, the dentition is succedaneous with 3 phases-primary dentition, mixed
      dentition, and permanent dentition-mandating different treatment protocols. This
      article is written for nondental providers to diagnose and treat dentoalveolar
      injuries. 

PMID- 24138740
TI  - Traumatic facial nerve injury.
AB  - Facial nerve trauma can be a devastating injury resulting in functional deficits
      and psychological distress. Deciding on the optimal course of treatment for
      patients with traumatic facial nerve injuries can be challenging, as there are
      many critical factors to be considered for each patient. Choosing from the great
      array of therapeutic options available can become overwhelming to both patients
      and physicians, and in this article, the authors present a systematic approach to
      help organize the physician's thought process. 

PMID- 24138741
TI  - Reconstruction of the avulsed auricle after trauma.
AB  - Severe auricular trauma is a rare injury. In addition to the type of injury, the
      location and the extent of the involved auricular structures have an important
      influence on the selection of an appropriate replantation or reattachment
      technique. A satisfactory primary reconstruction is not always possible to obtain
      and the remaining defects must be reconstructed secondary. The localization of
      the defect, its extent, and the condition of the tissue surrounding the defect
      are essential criteria for further treatment planning. This article provides an
      overview of the treatment of acute auricular trauma and of important aspects of
      secondary defect repair of the pinna. 

PMID- 24138742
TI  - Secondary repair of acquired enophthalmos.
AB  - In the setting of facial trauma with fracture of one or more orbital walls,
      clinically significant enophthalmos is a possible undesirable outcome after
      primary repair. In this article, the evaluation of patients presenting with
      acquired enophthalmos and the available minimally invasive and surgical
      management options are discussed. 

PMID- 24138743
TI  - Improving posttraumatic facial scars.
AB  - Posttraumatic soft-tissue injuries of the face are often the most lasting
      sequelae of facial trauma. The disfigurement of posttraumatic scarring lies in
      both their physical deformity and psychosocial ramifications. This review
      outlines a variety of techniques to improve facial scars and limit their lasting
      effects. 

PMID- 24138744
TI  - Facial transplantation for massive traumatic injuries.
AB  - This article describes the challenges of facial reconstruction and the role of
      facial transplantation in certain facial defects and injuries. This information
      is of value to surgeons assessing facial injuries with massive soft tissue loss
      or injury. 

PMID- 24138745
TI  - Application of autologous free tissue transfer in the management of massive
      traumatic tissue loss.
AB  - This review describes a general approach and philosophy in the management of
      massive facial trauma with extensive tissue loss, with particular highlight on
      the role of free tissue transfer. 

PMID- 24138746
TI  - Contemporary management of facial trauma.

PMID- 24138747
TI  - Evaluation of the national roll-out of parenting programmes across England: the
      parenting early intervention programme (PEIP).
AB  - BACKGROUND: Evidence based parenting programmes can improve parenting skills and
      the behaviour of children exhibiting, or at risk of developing, antisocial
      behaviour. In order to develop a public policy for delivering these programmes it
      is necessary not only to demonstrate their efficacy through rigorous trials but
      also to determine that they can be rolled out on a large scale. The aim of the
      present study was to evaluate the UK government funded national implementation of
      its Parenting Early Intervention Programme, a national roll-out of parenting
      programmes for parents of children 8-13 years in all 152 local authorities (LAs)
      across England. Building upon our study of the Pathfinder (2006-08) implemented
      in 18 LAs. To the best of our knowledge this is the first comparative study of a
      national roll-out of parenting programmes and the first study of parents of
      children 8-13 years. METHODS: The UK government funded English LAs to implement
      one or more of five evidence based programmes (later increased to eight): Triple
      P, Incredible Years, Strengthening Families Strengthening Communities, Families
      and Schools Together (FAST), and the Strengthening Families Programme (10-14).
      Parents completed measures of parenting style (laxness and over-reactivity), and
      mental well-being, and also child behaviour at three time points: pre- and post
      course and again one year later. RESULTS: 6143 parents from 43 LAs were included
      in the study of whom 3325 provided post-test data and 1035 parents provided data
      at one-year follow up. There were significant improvements for each programme,
      with effect sizes (Cohen's d) for the combined sample of 0.72 parenting laxness,
      0.85 parenting over-reactivity, 0.79 parent mental well-being, and 0.45 for child
      conduct problems. These improvements were largely maintained one year later. All
      four programmes for which we had sufficient data for comparison were effective.
      There were generally larger effects on both parent and child measures for Triple
      P, but not all between programme comparisons were significant. Results for the
      targeted group of parents of children 8-13 years were very similar. CONCLUSIONS:
      Evidence-based parenting programmes can be rolled out effectively in community
      settings on a national scale. This study also demonstrates the impact of research
      on shaping government policy.

PMID- 24138748
TI  - Adherence to treatment guidelines and survival in triple-negative breast cancer:
      a retrospective multi-center cohort study with 9,156 patients.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) remains a challenging topic for
      clinical oncologists. This study sought to evaluate TNBC versus other breast
      cancer subtypes with respect to survival parameters. We evaluated possible
      differences in survival in TNBC by age and by the extent to which evidence-based
      treatment guidelines were adhered. METHODS: This German retrospective multi
      center cohort study included 9156 patients with primary breast cancer recruited
      from 1992 to 2008. RESULTS: The rates of guideline adherence are significantly
      lower in TNBC compared to non-TNBC subtypes. These lower rates of guideline
      adherence can be observed in all age groups and are most pronounced in the >65
      subgroup [<50 (20.9% vs. 42.0%), 50-64 (25.1% vs. 51.1%), and >65 (38.4% vs.
      74.6%)]. In TNBC patients of all age groups, disease-free survival and overall
      survival were associated with an improvement by 100% guideline-adherent adjuvant
      treatment compared to non-adherence. Furthermore, TNBC patients of all ages had
      similar outcome parameters if 100% guideline-adherent adjuvant treatment was
      applied. CONCLUSION: The rates of guideline-adherent treatment were significantly
      lower in TNBC, even though guideline adherence was strongly associated with
      improved survival. In the case of 100% guideline-adherent treatment, no
      difference in survival was observed over all the age groups examined, even in the
      group of >65-year-old TNBC patients.

PMID- 24138749
TI  - Observation of room temperature B-Cl activation of the HCB11Cl11(-) anion and
      isolation of a stable anionic carboranyl phosphazide.
AB  - The perchlorinated carba-closo-dodecaborate anion is typically inert toward B-Cl
      functionalization. We present here the observation of two competing reactions
      that occur with this anion at ambient temperature. When this molecule is treated
      with n-BuLi and subsequently reacted with tosyl azide, a cycloaddition occurs and
      results in chloride substitution at a B-Cl vertex. The competing and dominant
      pathway is a substitution reaction to form the azide N3CB11Cl11(-). This rare
      anionic carboranyl azide reacts with PPh3 in FC6H5 to afford a stable anionic
      phosphazide. When dissolved in tetrahydrofuran, the phosphazide is in equilibrium
      with free PPh3 and N3CB11Cl11(-). Both the triazole and phosphazide are
      characterized by single-crystal X-ray diffraction, NMR and IR spectroscopy, and
      high-resolution mass spectrometry. 

PMID- 24138750
TI  - Bionanocomposites: differential effects of cellulose nanocrystals on protein
      diblock copolymers.
AB  - We investigate the effects of mixing a colloidal suspension of tunicate-derived
      cellulose nanocrystals (t-CNCs) with aqueous colloidal suspensions of two protein
      diblock copolymers, EC and CE, which bear two different self-assembling domains
      (SADs) derived from elastin (E) and the coiled-coil region of cartilage
      oligomeric matrix protein (C). The resulting aqueous mixtures reveal improved
      mechanical integrity for the CE+t-CNC mixture, which exhibits an elastic gel
      network. This is in contrast to EC+t-CNC, which does not form a gel, indicating
      that block orientation influences the ability to interact with t-CNCs. Surface
      analysis and interfacial characterization indicate that the differential
      mechanical properties of the two samples are due to the prevalent display of the
      E domain by CE, which interacts more with t-CNCs leading to a stronger network
      with t-CNCs. On the other hand, EC, which is predominantly C-rich on its surface,
      does not interact as much with t-CNCs. This suggests that the surface
      characteristics of the protein polymers, due to folding and self-assembly, are
      important factors for the interactions with t-CNCs, and a significant influence
      on the overall mechanical properties. These results have interesting implications
      for the understanding of cellulose hydrophobic interactions, natural biomaterials
      and the development of artificially assembled bionanocomposites. 

PMID- 24138751
TI  - Evaluation of factors associated with noncompliance in users of combined hormonal
      contraceptive methods: a cross-sectional study: results from the MIA study.
AB  - BACKGROUND: Understanding contraception from the perspective of the user may help
      to improve compliance. The aim of this project was to determine the factors that
      influence the noncompliance in young women that use combined hormonal
      contraceptives (pill, patch or vaginal ring). METHODS: A nationwide cross
      sectional multicenter epidemiology study. Physicians
      [obstetricians/gynecologists]) recorded socio-demographic, clinical and current
      contraception data of 8,762 women. Women completed a self-administered
      questionnaire on compliance. After the assessment of self-administrated
      questionnaire, the physicians reported on their recommendations on the
      possibility of changing the contraceptive. RESULTS: Fifty-two percent of women
      were noncompliant, mainly because of simple forgetfulness (pill, 74.9%; patch,
      47.8%; vaginal ring, 69.1%). The percentage of noncompliant women was lower in
      vaginal ring users (26.6%) than in patch users (42.4%) or pill users (65.1%) (p <
      0.0001). The most common course of action after noncompliance was to take/use the
      contraceptive as soon as possible. In the multiple logistic regression analysis,
      the use of the pill increased the probability of noncompliance compared with the
      patch and the vaginal ring (odds ratio [IC95%]: 2.53 (2.13-3.02) and 4.17 (3.68
      4.73, respectively), and using the patch compared with the vaginal ring (1.65
      (1.36-1.99)). Others factors associated with noncompliance were: high treatment
      duration, low degree of information on the contraceptive method, understanding of
      instructions on the contraceptive method, indifference to becoming pregnant, lack
      of partner support, not participation in selecting the method, not having a
      routine for taking treatment and difficulties remembering use the contraceptive
      method. Switching contraceptive method was proposed by the physicians to 43.2% of
      women (51.8% of pill users, 58.2% of patch users and 19.4% of vaginal ring
      users). CONCLUSIONS: More than 50% of combined hormonal contraceptive users did
      not comply with the treatment regimen. The percentage of noncompliant women was
      lower between vaginal ring users. Understanding user's reasons for noncompliance
      by the clinician and encouraging a collaborative approach can go a long way to
      improving compliance.

PMID- 24138752
TI  - Comprehensive analysis of the percentage of surface receptors and cytotoxic
      granules positive natural killer cells in patients with pancreatic cancer,
      gastric cancer, and colorectal cancer.
AB  - BACKGROUND: Digestive malignancies, especially pancreatic cancer (PC), gastric
      cancer (GC), and colorectal cancer (CRC), still occur at persistently high rates,
      and disease progression in these cancers has been associated with tumor
      immunosurveillance escape. Natural killer (NK) cell dysfunction may be
      responsible for this phenomenon, however, the exact relationship between tumor
      immunosurveillance escape in digestive malignancies and NK cell dysfunction
      remains unclear. METHODS: Percentage of the surface receptors NKG2A, KIR3DL1,
      NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granules
      perforin and granzyme B positive NK cells were determined in patients with
      pancreatic cancer (n=31), gastric cancer (n=31), and CRC (n=32) prior to surgery
      and healthy controls (n=31) by multicolor flow cytometry. Independent t-tests or
      Mann-Whitney U-tests were used to compare the differences between the patient and
      healthy control groups, as well as the differences between patients with
      different pathologic features of cancer. RESULTS: Percentage of NKG2D, NKp30,
      NKp46, and perforin positive NK cells was significantly down-regulated in
      patients with PC compared to healthy controls, as well as GC and CRC; reduced
      levels of these molecules was associated with indicators of disease progression
      in each malignancy (such as histological grade, depth of invasion, lymph node
      metastasis). On the contrary, percentage of KIR3DL1 positive NK cells was
      significantly increased in patients with PC, as well as GC and CRC, but was not
      associated with any indicators of disease progression. CONCLUSIONS: Altered
      percentage of surface receptors and cytotoxic granules positive NK cells may play
      a vital role in tumor immunosurveillance escape by inducing NK cell dysfunction
      in patients with PC, GC, and CRC.

PMID- 24138753
TI  - Spermatozoa of the old endemic rodents of Australia - the possible functional
      significance of their ventral processes.
AB  - Spermatozoa of the plains mouse (Pseudomys australis), like those of most
      Australian old endemic rodents, contain, in addition to an apical hook, two
      further processes that extend from the upper concave surface of the head, the
      ventral processes. This study shows that these processes contain thiol-rich
      cytoskeletal proteins, which presumably help to maintain their rigidity during
      sperm transport, together with the overlying cell membrane having abundant
      intramembranous proteins. To determine the possible functional significance of
      these processes, an in vitro study of spermatozoon-zona binding was undertaken.
      The findings suggest that initial sperm binding occurs by way of the cell
      membrane over the acrosome of the apical hook and that, subsequently, the lateral
      surfaces of the ventral processes also become tightly bound to the zona matrix.
      These ventral processes may therefore have evolved to increase sperm adhesion to
      the outer zona surface and/or to enhance stabilisation of the spermatozoon at the
      time of zona binding and initial penetration of the egg coat. 

PMID- 24138754
TI  - Reply: To PMID 23219064.

PMID- 24138755
TI  - Inadvertent trypan blue posterior capsule staining during cataract surgery.

PMID- 24138756
TI  - The effect of prior trabeculectomy on refractive outcomes of cataract surgery.

PMID- 24138757
TI  - Reply: To PMID 23398980.

PMID- 24138758
TI  - Roles played by histamine in strenuous or prolonged masseter muscle activity in
      mice.
AB  - Bruxism and/or clenching, resulting in fatigue or dysfunction of masseter muscles
      (MM), may cause temporomandibular disorders. Functional support of the
      microcirculation is critical for prolonged muscle activity. Histamine is a
      regulator of the microcirculation and is supplied by release from its stores
      and/or by de novo production via the induction of histidine decarboxylase (HDC).
      Interleukin (IL)-1, a cytokine involved in temporomandibular disorders, is an
      inducer of HDC. In the present study, we examined the roles of histamine, HDC and
      IL-1 in MM activity. Experiments were conducted using our R+G+ model. A mouse
      restrained (R+) inside a narrow cylinder (front end blocked with a thin plastic
      strip) gnaws away (G+) the strip to escape, with the weight reduction in the
      strip serving as an index of MM activity. Fexofenadine (a peripherally acting
      histamine H1 receptor antagonist) reduced MM activity in normal mice. Both H1
      receptor-deficient and HDC-deficient mice exhibited low MM activity. Prolonged
      R+G+ induced HDC activity in MM. Mast cell-deficient mice exhibited strikingly
      low HDC induction in MM (and also in the quadriceps femoris muscle) in response
      to muscle activity or IL-1beta. Mast cells were present around blood vessels and
      nerves in the epimysium and perimysium of MM. These results, together with others
      reported previously, suggest that: (i) peripheral histamine supports strenuous MM
      activity; (ii) strenuous MM activity stimulates mast cells to release histamine
      and to induce HDC (which replenishes the histamine pool in mast cells, possibly
      mediated by IL-1); and (iii) peripheral histamine H1 receptor antagonists may be
      effective in treating temporomandibular disorders or preventing prolonged
      clenching and/or bruxism. 

PMID- 24138759
TI  - Endogenous expression of FAD-linked PS1 impairs proliferation, neuronal
      differentiation and survival of adult hippocampal progenitors.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by progressive memory loss
      and impaired cognitive function. Early-onset familial forms of the disease (FAD)
      are caused by inheritance of mutant genes encoding presenilin 1 (PS1) variants.
      We have demonstrated that prion promoter (PrP)-driven expression of human FAD
      linked PS1 variants in mice leads to impairments in environmental enrichment (EE)
      induced adult hippocampal neural progenitor cell (AHNPC) proliferation and
      neuronal differentiation, and have provided evidence that accessory cells in the
      hippocampal niche expressing PS1 variants may modulate AHNPC phenotypes, in vivo.
      While of significant interest, these latter studies relied on transgenic mice
      that express human PS1 variant transgenes ubiquitously and at high levels, and
      the consequences of wild type or mutant PS1 expressed under physiologically
      relevant levels on EE-mediated AHNPC phenotypes has not yet been tested. RESULTS:
      To assess the impact of mutant PS1 on EE-induced AHNPC phenotypes when expressed
      under physiological levels, we exposed adult mice that constitutively express the
      PSEN1 M146V mutation driven by the endogenous PSEN1 promoter (PS1 M146V "knock
      in" (KI) mice) to standard or EE-housed conditions. We show that in comparison to
      wild type PS1 mice, AHNPCs in mice carrying homozygous (PS1M146V/M146V) or
      heterozygous (PS1M146V/+) M146V mutant alleles fail to exhibit EE-induced
      proliferation and commitment towards neurogenic lineages. More importantly, we
      report that the survival of newborn progenitors are diminished in PS1 M146V KI
      mice exposed to EE-conditions compared to respective EE wild type controls.
      CONCLUSIONS: Our findings reveal that expression at physiological levels achieved
      by a single PS1 M146V allele is sufficient to impair EE-induced AHNPC
      proliferation, survival and neuronal differentiation, in vivo. These results and
      our finding that microglia expressing a single PS1 M146V allele impairs the
      proliferation of wild type AHNPCs in vitro argue that expression of mutant PS1 in
      the AHNPC niche impairs AHNPCs phenotypes in a dominant, non-cell autonomous
      manner.

PMID- 24138760
TI  - Time to blood culture positivity as a predictor of clinical outcome in patients
      with Candida albicans bloodstream infection.
AB  - BACKGROUND: Few studies have assessed the time to blood culture positivity as a
      predictor of clinical outcome in fungal bloodstream infections (BSIs). The
      purpose of this study was to evaluate the time to positivity (TTP) of blood
      cultures in patients with Candida albicans BSIs and to assess its impact on
      clinical outcome. METHODS: A historical cohort study with 89 adults patients with
      C. albicans BSIs. TTP was defined as the time between the start of incubation and
      the time that the automated alert signal indicating growth in the culture bottle
      sounded. RESULTS: Patients with BSIs and TTPs of culture of <= 36 h (n=39) and
      >36 h (n=50) were compared. Septic shock occurred in 46.2% of patients with TTPs
      of <= 36 h and in 40.0% of patients with TTP of >36 h (p=0.56). A central venous
      catheter source was more common with a BSI TTP of <= 36 h (p=0.04). Univariate
      analysis revealed that APACHE II score >= 20 at BSI onset, the development of at
      least one organ system failure (respiratory, cardiovascular, renal, hematologic,
      or hepatic), SOFA at BSI onset, SAPS II at BSI onset, and time to positivity were
      associated with death. By using logistic regression analysis, the only
      independent predictor of death was time to positivity (1.04; 95% CI, 1.0-1.1,
      p=0.035), with the chance of the patient with C. albicans BSI dying increasing
      4.0% every hour prior to culture positivity. CONCLUSION: A longer time to
      positivity was associated with a higher mortality for Candida albicans BSIs;
      therefore, initiating empiric treatment with antifungals may improve outcomes.

PMID- 24138761
TI  - Examining refeeding protocols for adolescents with anorexia nervosa (again):
      challenges to current practices.

PMID- 24138762
TI  - The promise of worksite parent-based HIV prevention for youth.

PMID- 24138763
TI  - Young adults remain worse off than adolescents.
AB  - On a broad range of indicators pertaining to risk taking and access to care,
      young adults fare worse than younger adolescents or older adults. Vulnerable
      groups, such as those facing chronic illness and those with unstable living
      arrangements, fare especially poorly as they transition to adulthood.
      Fortunately, a confluence of factors, particularly the changing nature of the
      transition to adulthood in modern society, has led to renewed interest in this
      critical period of the life cycle. Health science research is increasingly
      focused on issues faced by young adults, and public health policies designed
      specifically to address the health and well-being of young adults--notably the
      Patient Protection and Affordable Care Act in the United States--are now being
      implemented. Successful efforts at improving the health and well-being of
      adolescents should be mirrored in efforts to support young adults. A new report
      based on a broad range of United States national datasets lays out the challenges
      that must be addressed in these efforts.

PMID- 24138764
TI  - Characteristics associated with initiation of the human papillomavirus vaccine
      among a national sample of male and female young adults.
AB  - PURPOSE: To examine rates of human papillomavirus vaccine initiation, and
      characteristics associated with initiation, among a national sample of male and
      female young adults. METHODS: Participants (n = 3,448; 48% female) were recruited
      using a Web-based, respondent-driven sampling strategy and completed a Web-based
      survey between October and December 2010. RESULTS: A total of 45% of females and
      4% of males initiated the vaccine. Females who were younger, never married, were
      in school, attended religious services less than once a month, were sexually
      active, and reported a greater number of lifetime sex partners, and who had been
      tested for human immunodeficiency virus were more likely to report initiation.
      Males who were African-American, attended religious services less than once a
      month, and reported a greater number of sex partners in their lifetime, and who
      had been tested for human immunodeficiency virus were more likely to report
      initiation. CONCLUSIONS: Factors associated with human papillomavirus vaccine
      initiation may differ for males and females. Further research with larger samples
      of males is needed to fully understand characteristics associated with male
      initiation. Regardless of gender, however, most young adults who have not
      initiated sexual activity have not received the vaccine. Further research is
      needed to examine how to increase vaccination rates among this population,
      because they may benefit most from vaccination.

PMID- 24138765
TI  - Uptake, coverage, and completion of quadrivalent human papillomavirus vaccine in
      the vaccine safety Datalink, July 2006-June 2011.
AB  - PURPOSE: The Advisory Committee on Immunization Practices recommended
      quadrivalent human papillomavirus vaccine (HPV4) for use in females in June 2006
      and in males in October 2009. The objective of our study was to describe HPV4
      uptake, single-dose coverage, and completion of the three-dose series among those
      9-26 years of age, after the respective female and male vaccine licensures
      through June 2011. METHODS: The study population included members of eight
      managed care organizations participating in the Vaccine Safety Datalink; we
      abstracted demographic and comprehensive vaccine information from electronic
      health records. RESULTS: We found one-dose coverage increasing throughout the
      study period, to a high of 37.7% among females and 1.3% among males in June 2011.
      Among those receiving at least one HPV4 dose, three-dose series completion was
      42% for females and 30.2% for males. CONCLUSIONS: Our results demonstrate low
      initiation and completion of the HPV4 series among those recommended to receive
      the vaccine. Although consistent with previous studies, these results highlight
      the continued need to develop, implement, and monitor strategies to increase HPV4
      vaccine initiation and completion in younger adolescents to achieve maximum
      impact in reducing the burden of cervical cancer and other HPV-related diseases.

PMID- 24138766
TI  - Household contact investigation for tuberculosis in Vietnam: study protocol for a
      cluster randomized controlled trial.
AB  - BACKGROUND: Tuberculosis is an infectious disease that continues to cause
      considerable morbidity and mortality globally. Only 65% of patients worldwide are
      currently diagnosed. Contact investigation is a strategy that aims to increase
      case detection and reduce transmission of tuberculosis, yet there is little
      evidence to show its effectiveness. METHODS/DESIGN: We will conduct a cluster
      randomized controlled trial of contact investigation within the national
      tuberculosis control program of Vietnam. Household contacts of patients with
      smear-positive pulmonary tuberculosis will be invited to attend district
      tuberculosis units for symptom screening, examination, and chest radiography on
      four occasions over a two-year period. The primary endpoint is clinically
      confirmed tuberculosis among contacts during the 24 months of follow-up,
      ascertained using capture-recapture analysis. Microbiologically proven
      tuberculosis and treatment completion rates among contacts diagnosed with
      tuberculosis will be secondary endpoints. The incremental cost-effectiveness
      ratio will be estimated. The study will have 80% power to detect a 50% increase
      in the primary endpoint in the active intervention arm compared with the control
      arm. The study will include 8,829 contacts in each of the active screening and
      control groups, within 70 districts in 8 provinces in Vietnam, in both rural and
      urban settings. DISCUSSION: The effectiveness of contact investigation as a tool
      for improved tuberculosis case finding has not been established. This cluster
      randomized trial will provide valuable operational information for national
      tuberculosis programs in high-prevalence countries, in order to select the most
      cost-effective strategies to improve tuberculosis case detection. TRIAL
      REGISTRATION: The ACT2 study has been registered with the Australian New Zealand
      Clinical Trials Registry (ACTRN12610000600044).

PMID- 24138767
TI  - [Therapeutic hypothermia for severe traumatic brain injury].
AB  - Therapeutic hypothermia (TH) is considered a standard of care in the post
      resuscitation phase of cardiac arrest. In experimental models of traumatic brain
      injury (TBI), TH was found to have neuroprotective properties. However, TH failed
      to demonstrate beneficial effects on neurological outcome in patients with TBI.
      The absence of benefits of TH uniformly applied in TBI patients should not
      question the use of TH as a second-tier therapy to treat elevated intracranial
      pressure. The management of all the practical aspects of TH is a key factor to
      avoid side effects and to optimize the potential benefit of TH in the treatment
      of intracranial hypertension. Induction of TH can be achieved with external
      surface cooling or with intra-vascular devices. The therapeutic target should be
      set at a 35 degrees C using brain temperature as reference, and should be
      maintained at least during 48 hours and ideally over the entire period of
      elevated intracranial pressure. The control of the rewarming phase is crucial to
      avoid temperature overshooting and should not exceed 1 degrees C/day. Besides its
      use in the management of intracranial hypertension, therapeutic cooling is also
      essential to treat hyperthermia in brain-injured patients. In this review, we
      will discuss the benefit-risk balance and practical aspects of therapeutic
      temperature management in TBI patients.

PMID- 24138768
TI  - [Risk of barotrauma when using non-reinhalation Waters valves: a comparative
      study on bench test].
AB  - OBJECTIVE: Manual ventilation is delivered in the operating room or the intensive
      care unit to intubated or non-intubated patients, using non-rebreathing systems
      such as the Waters valve. New generation Waters valves are progressively
      replacing the historic Waters valve. The aim of this study was to evaluate
      maximal pressure delivered by these 2 valves. TYPE OF STUDY: Bench test. MATERIAL
      AND METHOD: Thirty-two different conditions were tested, according to 2 oxygen
      flow rates (10 and 20L/min), without (static condition) or with manual
      insufflations (dynamic condition) and 4 valve expiratory opening pressures. The
      primary endpoint was maximal pressure measured at the exit of the valve,
      connected to a model lung and a bench test. RESULTS: Measured pressures were
      different for most evaluated conditions. Increasing oxygen flow from 10 to
      20L/min increased maximal pressure for both valves. Increasing valve expiratory
      opening pressure induced a significant increase in maximal pressure for the new
      generation valve (from 4 to 61cmH2O in static conditions and from 18 to 68cmH2O
      in dynamic conditions). For the historic valve, maximal pressure increased
      significantly but remained below 15cmH2O in both static and dynamic conditions.
      CONCLUSION: Use of new generation Waters valves should be different from historic
      Waters valves. Indeed, barotrauma could be caused by badly adapted valve
      expiratory opening pressure settings.

PMID- 24138769
TI  - [Chronic pain after cesarean: Impact and risk factors associated].
AB  - BACKGROUND: Chronic postoperative pain is a well-recognized problem after
      amputation, thoracotomy, mastectomy and inguinal hernia repair but has not been
      well evaluated after obstetric surgery. STUDY DESIGN: Retrospective cohort.
      OBJECTIVES: To determine the rate of chronic pain after cesarean, their impact on
      quality of life of patients and risk factors associated with this complication.
      METHODS: A questionnaire was sent to 220 consecutive patients who underwent
      caesarean delivery in a 6-month period. The questions focused on the duration of
      incisional pain after caesarean, severity and impact on daily activities.
      Meanwhile, a retrospective collection of clinical data (history, details of
      surgery and anaesthesia) was performed. After a descriptive analysis of the study
      population, a comparison of patients with and without DCPC was conducted to
      highlight potential risk factors. RESULTS: One hundred and sixty-seven patients
      (76%) completed the survey. The average response time was 10months (range 8-12)
      after caesarean section. The postoperative pain was resoluted in most patients
      within three months but persisted in 25 patients (15%). Seven patients (4%)
      showed a deterioration of their quality of life because of daily moderate to
      severe incisional pain. Risk factors associated with chronic pain were the
      presence of acute pain in postoperative, pre-existing pain (headaches, back
      pain), a young age and the achievement of general anaesthesia without
      locoregional associated at caesarean section. CONCLUSION: The occurrence of
      chronic pain after cesarean section may be frequent and can be responsible for an
      impaired quality of life.

PMID- 24138770
TI  - [Regional survey of peripheral nerve block practice by French residents].
AB  - OBJECTIVES: There are limited data on peripheral nerve block (PNB) practices by
      residents in France, especially with after introduction of ultrasound. A survey
      was conducted on PNB practices by French residents. STUDY DESIGN: Multicenter
      prospective descriptive study. PATIENTS AND METHODS: All residents completed a
      survey form after each PNB procedure. RESULTS: A total of 394 procedures
      performed by 21 residents in 4 hospitals were collected. The number of procedures
      and average volume of local anesthetics by type of block are: axillary block 245
      25mL (62%), interscalene 29-21mL (7%), supraclavicular 1-25mL (0.3%), 2-25mL
      infraclavicular (0.5%), femoral 65-18mL (16.5%), sciatic 52-22mL (13%). Detection
      was done by ultrasound only for 365 (92.6%) procedures, and neurostimulation only
      for 23 (5.8%) procedures. The duration of procedure was less than 5min for 200
      (50.7%) procedures and more than 15min for 16 (4%) procedures. A single puncture
      was required for 307 (78%) procedures. The initial block success was obtained in
      369 (93%) procedures. High training level residents required less time
      (P<0.0001), less puncture (P<0.046) and less neurostimulation use (P<0.0001) than
      novices, without difference in success rate and the volume of local anesthetic
      required. CONCLUSIONS: The majority of procedures performed by the residents are
      using ultrasound. The procedure is usually fast, requiring mainly a single
      puncture and has a high rate of success.

PMID- 24138771
TI  - [Impact of the decrease of nitrous oxide use on the consumption of halogenated
      agents].
AB  - OBJECTIVE: Nitrous oxide (N2O) toxicity and its impact on pollution lead to
      restrict its use. A decrease of N2O consumption should increase the hypnotic
      inhaled consumption. This monocentric study estimated consumptions and costs of
      halogenated agents (HA) and N2O over 5 years when the N2O consumption was
      reduced. STUDY DESIGN: Retrospective from a computerized database. PATIENTS:
      Between 2006 and 2010, 34,097 procedures were studied after two meetings exposing
      the risks of the N2O. METHODS: At the end of anesthesia, consumptions of hypnotic
      agents (millilitres transmitted by the injectors and the blender) were archived
      in the database. The annual consumption of agents was obtained by adding the
      individual consumptions, then divided by the annual number of cases. The costs
      were given by the hospital pharmacy from invoices. RESULTS: N2O consumption per
      anesthesia constantly decreased during the study, from 75.1L by act to 22.7L. The
      sum of the annual consumptions of N2O and air did not change suggesting that
      total fresh gas flow remained stable. Between 2006 and 2010, the sevoflurane
      consumption by act increased by 25%, from 16.5 to 20.6mL, and desflurane
      consumption by 37%, from 46.1 to 63.1mL by patient. The costs of the
      administration of hypnotic agents remained stable. CONCLUSION: N2O consumption
      decrease had an impact on the consumption of HA. The cost reduction of the N2O
      was counterbalanced by the increase of halogenated vapor cost. The profit of the
      ecological impact of the reduction in N2O use could be quantified.

PMID- 24138772
TI  - Impact of noradrenaline infusion set on mean arterial pressure: a retrospective
      clinical study.
AB  - OBJECTIVES: Noradrenaline (NA) can be infused through various systems including
      single or double syringe pumps. The aim of this study was to define the best and
      most efficient infusion system in an emergency context. STUDY DESIGN: This was a
      retrospective clinical study based on the analysis of patients' hemodynamic data.
      PATIENTS AND METHOD: Three infusion lines used presently in our postoperative ICU
      were compared through a retrospective clinical study: an NA syringe pump at 2mL/h
      and a saline carrier solution syringe pump at 8mL/h (infusion system 1- IS1) or
      5mL/h (IS2), both connected to a very low dead-space volume set (V=0.046mL); IS3
      with the same NA syringe at 2mL/h directly connected to the central venous
      catheter. Mean arterial pressure (MAP) was obtained from retrospective data
      analysis of ICU patients with postoperative septic shock criteria. Infusion
      systems were compared according to the time required to reach an MAP greater than
      65mmHg after the onset of infusion. RESULTS: Data from 37 patients was analysed.
      The MAP objective was attained in 14:00 minutes (9:20 - 26:10, n=15) with IS1, in
      19:10 minutes (12:20 - 27:20, n=13) with IS2 and in 34:10 minutes (23:10 - 62:30,
      n=9) with IS3 (P=0.00032). CONCLUSION: The use of a double syringe pump system
      associated with a very low dead-space volume infusion set appears to be the most
      appropriate system for NA infusion.

PMID- 24138773
TI  - [Pathophysiology and management of post-cardiac arrest syndrome].
AB  - OBJECTIVE: This review aims at providing an update on post-cardiac arrest
      syndrome, from pathophysiology to treatment. DATA SOURCES: Medline database. DATA
      EXTRACTION: All data on pathophysiology, clinical manifestations and therapeutic
      management, with focus on the publications of the 5 last years. DATA SYNTHESIS:
      Care of the patients after cardiac arrest is a medical challenge, in face of
      "post-cardiac arrest syndrome", which culminates into multi-organ failure. This
      syndrome mimics sepsis-related dysfunctions, with all clinical and biological
      manifestations related to the phenomenon of global ischemia-reperfusion. Acute
      cardiocirculatory dysfunction is usually controlled through pharmacological and
      mechanical support. Meanwhile, as a majority of cardiac arrest is related to
      myocardial infarction, early angiographic exploration should then be discussed
      when there is no obvious extracardiac cause, percutaneous coronary
      revascularization being associated with improved short and long-term prognosis.
      Therapeutic hypothermia is the cornerstone of neuroprotective armamentarium,
      beyond hemodynamic stabilization and metabolic maintenance. CONCLUSION: If
      ongoing evaluations should shed light on potential efficiency of new therapeutic
      drugs, a multidisciplinary approach of the post-cardiac arrest syndrome in
      expertise centre is essential.

PMID- 24138774
TI  - Creating and supporting a mixed methods health services research team.
AB  - OBJECTIVE: To use the experience from a health services research evaluation to
      provide guidance in team development for mixed methods research. METHODS: The
      Research Initiative Valuing Eldercare (THRIVE) team was organized by the Robert
      Wood Johnson Foundation to evaluate The Green House nursing home culture change
      program. This article describes the development of the research team and provides
      insights into how funders might engage with mixed methods research teams to
      maximize the value of the team. RESULTS: Like many mixed methods collaborations,
      the THRIVE team consisted of researchers from diverse disciplines, embracing
      diverse methodologies, and operating under a framework of nonhierarchical, shared
      leadership that required new collaborations, engagement, and commitment in the
      context of finite resources. Strategies to overcome these potential obstacles and
      achieve success included implementation of a Coordinating Center, dedicated time
      for planning and collaborating across researchers and methodologies, funded
      support for in-person meetings, and creative optimization of resources.
      CONCLUSIONS: Challenges are inevitably present in the formation and operation of
      effective mixed methods research teams. However, funders and research teams can
      implement strategies to promote success.

PMID- 24138775
TI  - 'Just in case': the fertility information needs of teenagers and young adults
      with cancer.
AB  - Understanding the reproductive and fertility concerns of teenagers and young
      adults with cancer (TYA) is one aspect of comprehensive age appropriate care.
      However, limited options for fertility preservation, coupled with vague policy
      recommendations, give rise to variations in information-sharing between health
      care professionals and TYAs, particularly as it involves sensitive discussions
      regarding the short- and long-term effects of cancer and treatments on fertility
      and reproduction. This paper presents findings from a wider evaluation at a
      specialist unit for TYAs with cancer. Forty people participated in semi
      structured interviews, including 20 young people, parents and partners. Young
      people were between 2 months and 4 years from finishing treatment. Most young
      people received mixed levels of information on fertility and counselling before
      treatment. Diagnosis in the early teens meant how, and from whom, young people
      received information varied. Young women tended to receive incomplete
      information. The majority of young people were unaware of their fertility status
      after treatment had finished. Findings point to the inherent challenges that
      exist in ensuring young people aged between 13 and 25 years receive comprehensive
      information on their fertility and potential risk, as well as advice on how to
      determine their fertility status after treatment has finished. 

PMID- 24138777
TI  - Assessing medical decision making capacity among cancer patients: Preliminary
      clinical experience of using a competency assessment instrument.
AB  - OBJECT: This study investigates the usefulness of the Structured Interview for
      Competency and Incompetency Assessment Testing and Ranking Inventory (SICIATRI)
      for cancer patients, which is a structured interview that assesses a patient's
      competency in clinical practice. METHODS: The SICIATRI, originally developed to
      measure patients' competency to give informed consent, were administered referred
      cancer patients who needed for assessing medical decision making capacity. The
      usefulness of the SICIATRI was investigated retrospectively. Recommendation for
      modification of the SICIATRI for cancer patients if applicable were made by the
      research team. RESULTS: Among the 433 cancer patients referred for psychiatric
      consultation, 12 were administered the SICIATRI and all of the administration
      were conducted without big problems. All patients were 60 years or older. The
      most common purpose for competency evaluation was to analyze patients'
      understanding of the anti-cancer treatment proposed by oncologists, followed by
      their refusal of the treatment. Half of the patients (n = 6) were diagnosed with
      delirium and three among them were judged as having the most impaired status of a
      patient's competency. Two patients (17%) were diagnosed with major depression and
      another two (17%) were mental retardation and each one patient was diagnosed with
      dementia and past history of alcohol dependence. Among 6 patients without
      delirium 5 subjects including a dementia patient were judged as fully competent.
      Total of 5 small potential modifications of the SICIATRI for its use with
      Japanese cancer patients were recommended. SIGNIFICANCE OF RESULTS: Our
      experience suggests that the SICIATRI is a useful instrument for psycho-oncology
      clinical practice.

PMID- 24138776
TI  - Urban slum structure: integrating socioeconomic and land cover data to model slum
      evolution in Salvador, Brazil.
AB  - BACKGROUND: The expansion of urban slums is a key challenge for public and social
      policy in the 21st century. The heterogeneous and dynamic nature of slum
      communities limits the use of rigid slum definitions. A systematic and flexible
      approach to characterize, delineate and model urban slum structure at an
      operational resolution is essential to plan, deploy, and monitor interventions at
      the local and national level. METHODS: We modeled the multi-dimensional structure
      of urban slums in the city of Salvador, a city of 3 million inhabitants in
      Brazil, by integrating census-derived socioeconomic variables and remotely-sensed
      land cover variables. We assessed the correlation between the two sets of
      variables using canonical correlation analysis, identified land cover proxies for
      the socioeconomic variables, and produced an integrated map of deprivation in
      Salvador at 30 m * 30 m resolution. RESULTS: The canonical analysis identified
      three significant ordination axes that described the structure of Salvador census
      tracts according to land cover and socioeconomic features. The first canonical
      axis captured a gradient from crowded, low-income communities with corrugated
      roof housing to higher-income communities. The second canonical axis
      discriminated among socioeconomic variables characterizing the most marginalized
      census tracts, those without access to sanitation or piped water. The third
      canonical axis accounted for the least amount of variation, but discriminated
      between high-income areas with white-painted or tiled roofs from lower-income
      areas. CONCLUSIONS: Our approach captures the socioeconomic and land cover
      heterogeneity within and between slum settlements and identifies the most
      marginalized communities in a large, complex urban setting. These findings
      indicate that changes in the canonical scores for slum areas can be used to track
      their evolution and to monitor the impact of development programs such as slum
      upgrading.

PMID- 24138778
TI  - Open surgical secondary procedures after thoracic endovascular aortic repair.
AB  - OBJECTIVES: Improved outcomes of thoracic endovascular aortic repair (TEVAR)
      compared with open repair have changed the therapeutic paradigm of thoracic
      aortic lesions. As the number of TEVAR survivors has grown, reports of
      complications have similarly increased. Although secondary endovascular rescue
      measures are often undertaken, patients with serious complications are often
      converted, ultimately, to open repair. The aim of this study was to assess causes
      and midterm results of open surgical secondary procedures after thoracic
      endovascular aortic repair. METHODS: A total of 236 patients underwent TEVAR.
      Fourteen of these patients required open repair because of six aortobronchial
      fistulas, four retrograde type A dissections, two aneurysm enlargement without
      endoleak, one thoracic stent-graft collapse, and one aortoesophageal fistula.
      Eight (57.1%) patients underwent surgical repair using cardiopulmonary bypass.
      Six stent-grafts were totally removed, and eight stent-grafts were left in situ.
      Four patients underwent supracoronary ascending aorta replacement, and one an
      extensive replacement of the aortic arch through sternotomy. Three patients had
      descending aortic replacement through left thoracotomy combined with a total
      esophagectomy in one case. One patient was treated by ligation of the aortic
      arch, ascending to supraceliac abdominal aorta bypass and stent-graft
      explantation. One patient was treated by exclusion bypass of the descending
      thoracic aorta. Pulmonary resection and large pleural or intercostal muscle flap
      interposition to wrap the stent-graft left in situ was done in four cases of
      aortobronchial fistula. RESULTS: All patients survived the surgical procedure.
      Ten patients (71%) had an uneventful postoperative course. There were two in
      hospital deaths (14.3%). Both died from multi-organ failure in the early
      postoperative course after surgical repair of a stent-graft infection and an
      aortoesophageal fistula. One patient suffered a definitive paraplegia and a
      secondary aortoesophageal fistula requiring reoperation for esophageal repair.
      One patient, treated by pulmonary resection and flap interposition to wrap the
      stent-graft, underwent stent-graft explantation and in situ descending aortic
      replacement because of stent-graft reinfection. Actuarial survival was 87.7%
      after a mean follow-up of 26.3 months (range 9-72 months). CONCLUSIONS:
      Complications or prevention of complications after TEVAR either due to device
      failure or adverse events may require conversion to open repair or additional
      open surgical procedure. Open repair can be performed by a team experienced in
      management of diseases of the thoracic aorta and a low mortality rate achieved
      despite the precarious preoperative conditions and complex aortic pathologies of
      patients.

PMID- 24138779
TI  - Indapamide-induced transient myopia with supraciliary effusion: case report.
AB  - BACKGROUND: Ingestion of sulphonamide-derived drugs has been reported to possibly
      have ocular side-effects. Authors aimed to present a rare case of indapamide
      induced transient myopia with ciliary body edema and supraciliary effusion. CASE
      PRESENTATION: A 39 years old caucasian female patient presented at the Department
      of Neurology with headache and sudden bilateral loss of distant vision.
      Neurological assessment and cranial CT scans were unremarkable. For her
      hypertension, twice a day bisoprolol 2.5 mg and once a day indapamide 1.5 mg
      tablets were prescribed several days before. At her presenting, ophthalmic
      findings were as follows: visual acuity 0.08-7.25Dsph = 1.0 and 0.06-7.25Dsph =
      1.0; IOP 25 mmHg and 24 mmHg, anterior chamber depth (ACD) 2.32 mm and 2.49 mm,
      lens thickness (L) 4.02 mm and 4.09 mm in the right and the left eye,
      respectively. By means of ultrasound biomicroscopy (UBM), thickened (720 / 700
      micron) and detached ciliary body, its forward movement (ciliary body-cornea
      angle 108' / 114') and forward rotated ciliary processes were seen. Angle opening
      distance (AOD500) were 300 / 314 microns. By the following days, the myopia
      gradually diminished, and a week after her first symptoms, her uncorrected visual
      acuity was 1.0 in both eyes, IOP 13 mmHg and 17 mmHg, ACD 3.68 mm and 3.66 mm, L
      3.78 mm and 3.81 mm in the right and the left eye, respectively. Ciliary body
      edema and detachment disappeared (ciliary body thickness 225 / 230 micron), both
      of the ciliary body-cornea angle 134' / 140' and the AOD500 (650 / 640 microns)
      increased. At this point, the patient admitted that she had stopped taking
      indapamide two days before. CONCLUSIONS: Our case report is the third one in the
      literature to present indapamide-induced transient myopia, and the first to
      employ UBM for describing the characteristics of this rare condition. According
      to the findings, authors suggest that both ciliary muscle contraction and ciliary
      body edema may play role in the pathomechanism. UBM seems to be a useful tool in
      the differential diagnosis of acute myopia. Further, authors wish to draw
      attention to one of the potential adverse effects of this drug which was not
      listed by its package insert.

PMID- 24138780
TI  - Peptide docking and structure-based characterization of peptide binding: from
      knowledge to know-how.
AB  - Peptide-mediated interactions are gaining increased attention due to their
      predominant roles in the many regulatory processes that involve dynamic
      interactions between proteins. The structures of such interactions provide an
      excellent starting point for their characterization and manipulation, and can
      provide leads for targeted inhibitor design. The relatively few experimentally
      determined structures of peptide-protein complexes can be complemented with an
      outburst of modeling approaches that have been introduced in recent years, with
      increasing accuracy and applicability to ever more systems. We review different
      methods to address the considerable challenges in modeling the binding of a short
      yet highly flexible peptide to its partner. These methods apply an array of
      sampling strategies and draw from a recent amassing of knowledge about the
      biophysical nature of peptide-protein interactions. We elaborate on applications
      of these structure-based approaches and in particular on the characterization of
      peptide binding specificity to different peptide-binding domains and enzymes.
      Such applications can identify new biological targets and thus complement our
      current view of protein-protein interactions in living organisms. Accurate
      peptide-protein docking is of particular importance in the light of increased
      appreciation of the crucial functional roles of disordered regions and the many
      linear binding motifs embedded within. 

PMID- 24138781
TI  - Clinical prognostic indicators of dysphagia following prolonged orotracheal
      intubation in ICU patients.
AB  - INTRODUCTION: The development of postextubation swallowing dysfunction is well
      documented in the literature with high prevalence in most studies. However, there
      are relatively few studies with specific outcomes that focus on the follow-up of
      these patients until hospital discharge. The purpose of our study was to
      determine prognostic indicators of dysphagia in ICU patients submitted to
      prolonged orotracheal intubation (OTI). METHODS: We conducted a retrospective,
      observational cohort study from 2010 to 2012 of all patients over 18 years of age
      admitted to a university hospital ICU who were submitted to prolonged OTI and
      subsequently received a bedside swallow evaluation (BSE) by a speech pathologist.
      The prognostic factors analyzed included dysphagia severity rate at the initial
      swallowing assessment and at hospital discharge, age, time to initiate oral
      feeding, amount of individual treatment, number of orotracheal intubations,
      intubation time and length of hospital stay. RESULTS: After we excluded patients
      with neurologic diseases, tracheostomy, esophageal dysphagia and those who were
      submitted to surgical procedures involving the head and neck, our study sample
      size was 148 patients. The logistic regression model was used to examine the
      relationships between independent variables. In the univariate analyses, we found
      that statistically significant prognostic indicators of dysphagia included
      dysphagia severity rate at the initial swallowing assessment, time to initiate
      oral feeding and amount of individual treatment. In the multivariate analysis, we
      found that dysphagia severity rate at the initial swallowing assessment remained
      associated with good treatment outcomes. CONCLUSIONS: Studies of prognostic
      indicators in different populations with dysphagia can contribute to the design
      of more effective procedures when evaluating, treating, and monitoring
      individuals with this type of disorder. Additionally, this study stresses the
      importance of the initial assessment ratings.

PMID- 24138782
TI  - Antibacterial effects of Apis mellifera and stingless bees honeys on susceptible
      and resistant strains of Escherichia coli, Staphylococcus aureus and Klebsiella
      pneumoniae in Gondar, Northwest Ethiopia.
AB  - BACKGROUND: Honey is a natural substance produced by honeybees and has
      nutritional and therapeutic uses. In Ethiopia, honeys are used traditionally to
      treat wounds, respiratory infections and diarrhoea. Recent increase of drug
      resistant bacteria against the existing antibiotics forced investigators to
      search for alternative natural remedies and evaluate their potential use on
      scientific bases. Thus, the aim of this study was to evaluate the antibacterial
      effects of different types of honeys in Ethiopia which are used traditionally to
      treat different types of respiratory and gastrointestinal infections. METHODS:
      Mueller Hinton agar (70191) diffusion and nutrient broth culture medium assays
      were performed to determine susceptibility of Staphylococcus aureus (ATCC 25923),
      Escherichia coli (ATCC 25922) and resistant clinical isolates (Methicillin
      resistant Staphylococcus aureus(MRSA), Escherichia coli(R) and Klebsiella
      pneumoniae (R), using honeys of Apis mellifera and stingless bees in northern and
      north western Ethiopia. RESULTS: Honey of the stingless bees produced the highest
      mean inhibition (22.27 +/- 3.79 mm) compared to white honey (21.0 +/- 2.7 mm) and
      yellow honey (18.0 +/- 2.3 mm) at 50% (v/v) concentration on all the standard and
      resistant strains. Stingless bees honey was found to have Minimum Inhibitory
      Concentration (MIC) of 6.25% (6.25 mg/ml) for 80% of the test organisms compared
      to 40% for white and yellow Apis mellifera honeys. All the honeys were found to
      have minimum bactericidal concentration (MBC) of 12.5% (12.5 mg/ml) against all
      the test organisms. Staphylococcus aureus (ATCC 25923) was susceptible to
      amoxicillin, methicillin, kanamycine, tetracycline, and vancomycine standard
      antibiotic discs used for susceptibility tests. Similarly, Escherichia coli (ATCC
      25922) was found susceptible for kanamycine, tetracycline and vancomycine.
      Escherichia coli (ATCC 25922) has not been tested for amoxicillin ampicillin and
      methicillin. The susceptibility tests performed against Staphylococcus aureus
      (MRSA), Escherichia coli (R) and Klebsiella pneumoniae (R) using three of
      methicillin, erythromycin, ampicillin, Penicillin and amoxicillin discs were
      resistant. But, these drug resistant strains were susceptible to antibacterial
      agents found in the honeys and inhibited from 16 mm to 20.33 mm. CONCLUSIONS:
      Honeys in Ethiopia can be used as therapeutic agents for drug resistant bacteria
      after pharmaceutical standardization and clinical trials.

PMID- 24138784
TI  - Lower leg muscle strengthening does not redistribute plantar load in diabetic
      polyneuropathy: a randomised controlled trial.
AB  - BACKGROUND: Higher plantar pressures play an important role in the development of
      plantar foot ulceration in diabetic polyneuropathy and earlier studies suggest
      that higher pressures under the forefoot may be related to a decrease in lower
      leg muscle strength. Therefore, in this randomised controlled trial we evaluated
      whether lower-extremity strength training can reduce plantar pressures in
      diabetic polyneuropathy. METHODS: This study was embedded in an unblinded
      randomised controlled trial. Participants had diabetes and polyneuropathy and
      were randomly assigned to the intervention group (n = 48) receiving strength
      training during 24 weeks, or the control group (n = 46) receiving no
      intervention. Plantar pressures were measured in both groups at 0, 12, 24 and 52
      weeks. A random intercept model was applied to evaluate the effects of the
      intervention on peak pressures and pressure-time-integrals, displacement of
      center-of-pressure and the forefoot to rearfoot pressure-time-integral-ratio.
      RESULTS: Plantar pressure patterns were not affected by the strength training. In
      both the intervention and control groups the peak pressure and the pressure-time
      integral under the forefoot increased by 55.7 kPa (95% CI: 14.7, 96.8) and 2.0
      kPa.s (95% CI: 0.9, 3.2) over 52 weeks, respectively. Both groups experienced a
      high number of drop-outs, mainly due to deterioration of health status and lower
      extremity disabilities. CONCLUSIONS: Plantar pressures under the forefoot
      increase progressively over time in people with diabetic polyneuropathy, but in
      this study were not affected by strength training. Future intervention studies
      should take this increase of plantar pressure into account and alternative
      interventions should be developed to reduce the progressive lower extremity
      problems in these patients. TRIAL REGISTRATION: This study was embedded in a
      clinical trial with trial number NCT00759265.

PMID- 24138783
TI  - Thyroid hormones are associated with exposure to persistent organic pollutants in
      aging residents of upper Hudson River communities.
AB  - The aim of this study was to evaluate the association between persistent organic
      pollutants (POPs) and thyroid hormones in an aging population. Forty-eight women
      and 66 men, aged 55-74 years and living in upper Hudson River communities
      completed a questionnaire and provided blood specimens. Serum was analyzed for
      thyrotropin (thyroid stimulating hormone, TSH), free (fT4) and total thyroxine
      (T4), total triiodothyronine (T3), and for POPs. POPs included 39 polychlorinated
      biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and
      dichlorodiphenyldichloroethylene (DDE) determined by gas chromatography with
      electron capture detection (GC-ECD), and nine polybrominated diphenyl ethers
      (PBDEs) determined by high-resolution gas chromatography with high-resolution
      mass spectrometry detection (HRGC-HRMS). Multivariable linear regression analysis
      was used to evaluate associations between thyroid hormones and sums of POPs,
      adjusted for covariates and stratified by sex. Effects were expressed as
      differences in thyroid hormone levels associated with a doubling in the level of
      exposure. Among women, DDT+DDE increased T4 by 0.34MUg/dL (P=0.04) and T3 by
      2.78ng/dL (P=0.05). Also in women, sums of PCBs in conjunction with PBDEs
      elicited increases of 24.39-80.85ng/dL T3 (P<0.05), and sums of PCBs in
      conjunction with DDT+DDE elicited increases of 0.18-0.31MUg/dL T4 (P<0.05). For
      men estrogenic PCBs were associated with a 19.82ng/dL T3 decrease (P=0.003), and
      the sum of estrogenic PCBs in conjunction with DDT+DDE elicited an 18.02ng/dL T3
      decrease (P=0.04). Given age-related declines in physiologic reserve, the
      influence of POPs on thyroid hormones in aging populations may have clinical
      implications and merits further investigation. 

PMID- 24138785
TI  - Immune-mediated colitis: important to recognize and treat.

PMID- 24138786
TI  - Social and spatial patterns of obesity diffusion over three decades in a
      Norwegian county population: the HUNT Study.
AB  - BACKGROUND: In order to develop effective preventive strategies, knowledge of
      trends in socioeconomic and geographical differences in risk factor levels is
      important. The objective of this study was to examine social and spatial patterns
      of obesity diffusion in a Norwegian population during three decades. METHODS:
      Data on adults aged 30-69 years from three cross-sectional health surveys eleven
      years apart in the Nord-Trondelag Health Study, Norway, HUNT1 (1984-1986), HUNT2
      (1995-1997) and HUNT3 (2006-2008) were utilized. Body mass index (BMI) was used
      as a measure of obesity. Height and weight were measured clinically. Age
      standardized prevalences, absolute prevalence differences and ratios, prevalence
      odds ratios for BMI and the Relative Index of Inequality (RII) were calculated.
      Multilevel statistical models were fitted for analysing geographical patterns.
      RESULTS: The prevalence of obesity was systematically higher in groups with lower
      socio-economic status and increased successively in all groups in the population
      during the three decades. The relative socioeconomic inequalities in obesity
      measured by level of education did not change substantially in the period. In
      HUNT1 (1984-86) obesity was most prevalent among low educated women (14.1%) and
      in HUNT3 (2006-08) among low educated men (30.4%). The RII for men changed from
      2.60 to 1.91 and 2.36 in HUNT1, HUNT2 and HUNT3. In women the RIIs were 1.71,
      2.28 and 2.30 correspondingly. However, the absolute obesity prevalence
      inequalities increased, and a geographical diffusion from central to distal
      districts was observed from HUNT2 to HUNT3. CONCLUSIONS: The prevalence of
      obesity increased in all socioeconomic groups in this Norwegian adult county
      population from the 1980ies up to present time. The data did not suggest
      increasing relative inequalities, but increasing absolute socioeconomic
      differences and a geographical diffusion towards rural districts. Public health
      preventive strategies should be oriented to counteract the obesity epidemic in
      the population.

PMID- 24138787
TI  - Preserved endothelial function in human obesity in the absence of insulin
      resistance.
AB  - BACKGROUND: Insulin resistance (IR) is frequently associated with endothelial
      dysfunction and has been proposed to play a major role in cardiovascular disease
      (CVD). On the other hand, obesity has long been related to IR and increased CVD.
      However it is not known if IR is a necessary condition for endothelial
      dysfunction in human obesity, allowing for preserved endothelial function in
      obese people when absent. Therefore, the purpose of the study was to assess the
      relationship between IR and endothelial dysfunction in human obesity and the
      mechanisms involved. METHODS: Twenty non-insulin resistant morbid obese (NIR-MO),
      32 insulin resistant morbid obese (IR-MO), and 12 healthy subjects were included.
      Serum concentrations of glucose, insulin, interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), resistin and adiponectin were determined. IR was
      evaluated by HOMA-index. Endothelium-dependent relaxation to bradykinin (BK) in
      mesenteric microvessels was assessed in wire myograph. RESULTS: Serum IL-6, and
      TNF-alpha levels were elevated only in IR-MO patients while resistin was elevated
      and adiponectin reduced in all MO individuals. Mesenteric arteries from IR-MO,
      but not from NIR-MO subjects displayed blunted relaxation to BK. Vasodilatation
      was improved in IR-MO arteries by the superoxide scavenger, superoxide dismutase
      (SOD) or the mitochondrial-targeted SOD mimetic, mito-TEMPO. NADPH oxidase
      inhibitors (apocynin and VAS2870) and the nitric oxide synthase (NOS) cofactor,
      tetrahydrobiopterin failed to modify BK-induced vasodilatations. Superoxide
      generation was higher in vessels from IR-MO subjects and reduced by mito-TEMPO.
      Blockade of TNF-alpha with infliximab, but not inhibition of inducible NOS or
      cyclooxygenase, improved endothelial relaxation and decreased superoxide
      formation. CONCLUSIONS: Endothelial dysfunction is observed in human morbid
      obesity only when insulin resistance is present. Mechanisms involved include
      augmented mitochondrial superoxide generation, and increased systemic
      inflammation mediated by TNF-alpha. These findings may explain the different
      vascular risk of healthy vs unhealthy obesity.

PMID- 24138788
TI  - Patient-provider perceptions on engagement in HIV care in Argentina.
AB  - Approximately 30% of patients participating in the national antiretroviral
      therapy (ART) program in Argentina fail to achieve an undetectable viral load,
      and approximately 25% are not retained in care. This qualitative study was
      designed to explore and identify factors associated with engagement and retention
      in public and private health care in Buenos Aires, Argentina. Qualitative data
      from key informants (n = 12) and focus groups (n = 4 groups) of patients and
      providers from private and public HIV treatment facilities were recorded and
      transcribed. Predetermined and arising themes related to adherence, engagement,
      and retention in care were coded and analyzed using qualitative data analysis
      software. Reasons identified for patients' lack of adherence or engagement in
      care differed between patients and providers, and patients attributed limitations
      to low self-efficacy, fear and concerns about HIV, and lack of provider
      involvement in treatment. In contrast, providers viewed themselves as decision
      makers in patient care and patients as responsible for their own nonadherence due
      to lack of commitment to their own health or due to medication side effects.
      Patients reported health care system limitations and HIV concerns contributed to
      a lack of engagement, and providers identified limited HIV literacy and stigma as
      additional problems. Both agreed that chronic illness and substance addiction
      impacted adherence and retention, and agreed on the importance of trust, honesty,
      and communication in the patient-provider relationship. Results support the
      incorporation of system-, provider-, and patient-focused components into
      interventions to facilitate patient engagement, adherence, and retention in
      public and private settings in Argentina. 

PMID- 24138789
TI  - Role of viruses in the development of breast cancer.
AB  - The most common cancer worldwide among women is breast cancer. The initiation,
      promotion, and progression of this cancer result from both internal and external
      factors. The International Agency for Research on Cancer stated that 18-20% of
      cancers are linked to infection, and the list of definite, probable, and possible
      carcinogenic agents is growing each year. Among them, biological carcinogens play
      a significant role. In this review, data covering infection-associated breast and
      lung cancers are discussed and presented as possible involvements as pathogens in
      cancer. Because carcinogenesis is a multistep process with several contributing
      factors, we evaluated to what extent infection is significant, and concluded that
      members of the herpesvirus, polyomavirus, papillomavirus, and retrovirus families
      definitely associate with breast cancer. Detailed studies of viral mechanisms
      support this conclusion, but have presented problems with experimental settings.
      It is apparent that more effort needs to be devoted to assessing the role of
      these viruses in carcinogenesis, by characterizing additional confounding and
      synergistic effects of carcinogenic factors. We propose that preventing and
      treating infections may possibly stop or even eliminate certain types of cancers.

PMID- 24138790
TI  - Rate of increase in serum lactate level risk-stratifies infants after surgery for
      congenital heart disease.
AB  - OBJECTIVE: Increased blood lactate levels reflect tissue oxygen debt and might be
      indicative of low cardiac output. We hypothesized that the rate of increase in
      serum lactate would be an ideal marker to discriminate between infants at high
      and low risk of a poor outcome after surgical repair of congenital heart disease
      using cardiopulmonary bypass. METHODS: In the present prospective, observational
      study in a pediatric cardiac intensive care unit, infants (aged <12 months)
      undergoing cardiac surgery had serial whole blood lactate levels measured with
      every arterial blood gas drawn for the first 24 postoperative hours. The
      composite poor outcome included death, the need for extracorporeal support, and
      dialysis. RESULTS: The lactate levels were measured in 231 infants; 19 infants
      (8.2%) had a poor outcome. A lactate increase rate of 0.6 mmol/L/h had very good
      discriminatory ability (area under the curve [AUC], 0.89) with a sensitivity of
      90%, specificity of 84%, positive predictive value (PPV) of 34%, and negative
      predictive value (NPV) of 99%. Similar results were obtained for subgroups
      stratified by 1- or 2-ventricle heart disease and risk adjustment for congenital
      heart surgery (RACHS-1) score. In neonates (age <30 days) with single-ventricle
      physiology (n = 43, poor outcome = 8), a lactate increase of 0.6 mmol/L/h had
      near perfect discriminatory ability (AUC 0.99) with a sensitivity of 100%,
      specificity of 51%, PPV of 32%, and NPV of 100%. In 2-ventricle neonates (n = 43,
      poor outcome = 5), a lactate increase of 0.6 mmol/L/h also had near perfect
      discriminatory ability (AUC, 0.99), with a sensitivity of 100%, specificity of
      90%, PPV of 56%, and NPV of 100%. CONCLUSIONS: The postoperative lactate increase
      rate allows discrimination between infants at high and low risk of morbidity and
      mortality after congenital heart disease surgery, and the lactate level can be
      followed serially for the treatment response.

PMID- 24138791
TI  - Two-stage hybrid repair for a Kommerell diverticulum in a right-sided aortic arch
      associated with multivessel coronary disease and atrial septal defect.

PMID- 24138792
TI  - The characteristics of good thoracic surgical training.

PMID- 24138793
TI  - Transcriptional down-regulation of suppressor of cytokine signaling (SOCS)-3 in
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Tobacco is a leading environmental factor in the initiation of
      respiratory diseases and causes chronic obstructive pulmonary disease (COPD).
      Suppressor of cytokine signaling (SOCS) family members are involved in the
      pathogenesis of many inflammatory diseases and SOCS-3 has been shown to play an
      important role in the regulation, onset and maintenance of airway allergic
      inflammation indicating that SOCS-3 displays a potential therapeutic target for
      anti-inflammatory respiratory drugs development. Since chronic obstructive
      pulmonary disease (COPD) is also characterized by inflammatory changes and
      airflow limitation, the present study assessed the transcriptional expression of
      SOCS-3 in COPD. METHODS: Real-time PCR was performed to assess quantitative
      changes in bronchial biopsies of COPD patients in comparison to unaffected
      controls. RESULTS: SOCS-3 was significantly down-regulated in COPD at the
      transcriptional level while SOCS-4 and SOCS-5 displayed no change. CONCLUSIONS:
      It can be concluded that the presently observed inhibition of SOCS-3 mRNA
      expression may be related to the dysbalance of cytokine signaling observed in
      COPD.

PMID- 24138794
TI  - Computer-assisted counting of retinal cells by automatic segmentation after TV
      denoising.
AB  - BACKGROUND: Quantitative evaluation of mosaics of photoreceptors and neurons is
      essential in studies on development, aging and degeneration of the retina. Manual
      counting of samples is a time consuming procedure while attempts to
      automatization are subject to various restrictions from biological and
      preparation variability leading to both over- and underestimation of cell
      numbers. Here we present an adaptive algorithm to overcome many of these
      problems.Digital micrographs were obtained from cone photoreceptor mosaics
      visualized by anti-opsin immuno-cytochemistry in retinal wholemounts from a
      variety of mammalian species including primates. Segmentation of photoreceptors
      (from background, debris, blood vessels, other cell types) was performed by a
      procedure based on Rudin-Osher-Fatemi total variation (TV) denoising. Once 3
      parameters are manually adjusted based on a sample, similarly structured images
      can be batch processed. The module is implemented in MATLAB and fully documented
      online. RESULTS: The object recognition procedure was tested on samples with a
      typical range of signal and background variations. We obtained results with error
      ratios of less than 10% in 16 of 18 samples and a mean error of less than 6%
      compared to manual counts. CONCLUSIONS: The presented method provides a traceable
      module for automated acquisition of retinal cell density data. Remaining errors,
      including addition of background items, splitting or merging of objects might be
      further reduced by introduction of additional parameters. The module may be
      integrated into extended environments with features such as 3D-acquisition and
      recognition.

PMID- 24138795
TI  - Baseline benthic foraminiferal assemblages and habitat conditions in a sub-Arctic
      region of increasing petroleum development.
AB  - The aim of this study is to establish pre-impact baseline conditions for an
      Arctic region where petroleum activities are projected to increase in the coming
      decades. We characterize the spatial distribution of living benthic foraminifera
      in the Tromsoflaket-Ingoydjupet region of the Barents Sea and relate this to
      sediment properties and their associated metal concentrations. Metal
      concentrations of the sediments did not exceed threshold levels of harmful
      environmental effects, indicating that the area exhibits pre-impact baseline
      conditions. Foraminiferal assemblages reflect the pristine environment. Epifaunal
      species dominate in Tromsoflaket, a high energy environment characterized by
      coarse grained sediments. Infaunal species dominate in Ingoydjupet, a low energy
      environment characterized by fine grained sediments. Metal concentrations were
      slightly elevated in the fine grained sediments from Ingoydjupet which suggest
      that these areas may in the future serve as trapping zones for contaminants
      associated with discharges from nearby petroleum sites. 

PMID- 24138796
TI  - What are we doing to prepare the next generation of ecotoxicologists?

PMID- 24138797
TI  - Environmental drivers of small scale spatial variation in the reproductive
      schedule of a commercially important bivalve mollusc.
AB  - Understanding variability in reproductive schedules is essential to the
      management of recruitment limited fisheries such as that of Pecten maximus. Small
      scale (<5 km) variation in gonad condition and the onset of spawning of P.
      maximus were found among commercial scallop grounds in Isle of Man waters.
      Environmental and fishing drivers of these spatial patterns were investigated
      using a generalised additive model. Rate of change in temperature over the month
      prior to sampling was identified as the short term driver of gonad weight
      associated with the autumn spawning event. Long term drivers were average annual
      chlorophyll a concentration, scallop density, stratification index and shell
      size. The model explained 42.8% of deviance in gonad weight. Within site
      variation in gonad condition was high, indicating a "bet hedging" reproductive
      strategy which may decrease the chance of fertilisation especially at low
      densities. Therefore, areas protected from fishing, where scallop densities can
      increase may help buffer against reproductive failure. An increase in shell
      length from 100 mm to 110 mm equated to an increase of approximately 20% in gonad
      weight. Protecting scallops from fishing mortality until 110 mm (age four)
      compared to 100 mm (age three) may lead to an overall increase in lifetime
      reproductive output by a factor of 3.4.

PMID- 24138798
TI  - Improving the diagnosis of meningitis due to enterovirus and herpes simplex virus
      I and II in a tertiary care hospital.
AB  - BACKGROUND: Enterovirus and herpes simplex viruses are common causes of
      lymphocytic meningitis. The purpose of this study was to analyse the impact of
      the use molecular testing for Enteroviruses and Herpes simplex viruses I and II
      in all suspected cases of viral meningitis. METHODS: From November 18, 2008 to
      November 17, 2009 (phase II, intervention), all patients admitted with suspected
      viral meningitis (with pleocytosis) had a CSF sample tested using a nucleic acid
      amplification test (NAAT). Data collected during this period were compared to
      those from the previous one-year period, i.e. November 18, 2007 to November 17,
      2008 (phase I, observational), when such tests were available but not routinely
      used. RESULTS: In total, 2,536 CSF samples were assessed, of which 1,264 were
      from phase I, and 1,272 from phase II. Of this total, a NAAT for Enterovirus was
      ordered in 123 cases during phase I (9.7% of the total phase I sample) and in 221
      cases in phase II (17.4% of the total phase II sample). From these, Enterovirus
      was confirmed in 35 (28.5%, 35/123) patients during phase I and 71 (32.1%,
      71/221) patients during phase II (p = 0.107). The rate of diagnosis of meningitis
      by HSV I and II did not differ between the groups (13 patients, 6.5% in phase I
      and 13, 4.7% in phase II) (p = 1.0), from 200 cases in phase I and 274 cases in
      phase II. CONCLUSIONS: The number of cases diagnosed with enteroviral meningitis
      increased during the course of this study, leading us to believe that the
      strategy of performing NAAT for Enterovirus on every CSF sample with pleocytosis
      is fully justified.

PMID- 24138799
TI  - Diagnostic value and prognostic evaluation of Presepsin for sepsis in an
      emergency department.
AB  - INTRODUCTION: Presepsin levels are known to be increased in sepsis. The aim of
      this study was to evaluate the early diagnostic and prognostic value of Presepsin
      compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis
      (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score in septic patients in an emergency department (ED) and to investigate
      Presepsin as a new biomarker of sepsis. METHODS: This study enrolled 859
      consecutive patients with at least two diagnostic criteria for systemic
      inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang
      Hospital ED from December 2011 to October 2012, and 100 age-matched healthy
      controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis,
      and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score
      and APACHE II score were calculated at enrollment. Comparisons were analyzed
      using the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: On admission, the
      median levels of plasma Presepsin increased with sepsis severity. The areas under
      the receiver operating characteristic (AUC) curves of Presepsin were greater than
      those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock.
      The AUC of Presepsin for predicting 28-day mortality in septic patients was
      slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a
      combination of Presepsin and MEDS score or APACHE II score was significantly
      higher than that of MEDS score or APACHE II score alone in predicting severe
      sepsis, and was markedly higher than that of Presepsin alone in predicting septic
      shock and 28-day mortality in septic patients, respectively. Plasma Presepsin
      levels in septic patients were significantly higher in non-survivors than in
      survivors at 28 days' follow-up. Presepsin, MEDS score and APACHE II score were
      found to be independent predictors of severe sepsis, septic shock and 28-day
      mortality in septic patients. The levels of plasma Presepsin were positively
      correlated with PCT, MEDS score and APACHE II score in every septic group.
      CONCLUSION: Presepsin is a valuable biomarker for early diagnosis of sepsis, risk
      stratification, and evaluation of prognosis in septic patients in the ED.

PMID- 24138800
TI  - Visible ink: A flexible and individually tailored writing intervention for cancer
      patients.
AB  - OBJECTIVES: Subjective reports on the effectiveness of and satisfaction with
      writing interventions in medical populations have indicated that they can have a
      profound impact on patients. Further, past research on these programs has
      demonstrated that they can lead to a number of different positive outcomes
      depending on the personal characteristics of the participating patients and the
      type of writing with which they are tasked. For this reason, a flexible and
      individually tailored writing intervention may be particularly effective for
      patients, molding its approach to their desires and backgrounds. This paper
      examines Visible Ink, a writing program for cancer patients at Memorial Sloan
      Kettering Cancer Center (MSKCC) that follows this model. METHODS: At Visible
      Ink's First Fall Writing Festival in November 2012, an optional survey was
      provided to all program participants in attendance, capturing both quantitative
      and qualitative information on patient experiences in the program. Twenty-nine
      surveys were completed. RESULTS: The program appears to have a variety of
      positive effects, including fostering personal growth and providing a positive
      distraction. Respondents reported that they write in a number of different genres
      on topics both related and not related to their illnesses, which supports the
      flexible model of the program. All respondents indicated that they would
      recommend the program to others, and satisfaction with the program's general
      approach (i.e., individualized work with a writing coach) was unanimous. A few
      areas for potential improvement were also identified, most of which involved
      expanding the services and events offered by the program. SIGNIFICANCE OF
      RESULTS: Despite the limitations of this survey (e.g., small sample size and low
      response rate), its results support the promise of the Visible Ink model and
      demonstrate participants' satisfaction with the program. Future research can more
      thoroughly examine Visible Ink's effectiveness, and additional resources could
      enable the program to expand.

PMID- 24138801
TI  - 1H NMR-based metabolic profiling of human rectal cancer tissue.
AB  - BACKGROUND: Rectal cancer is one of the most prevalent tumor types. Understanding
      the metabolic profile of rectal cancer is important for developing therapeutic
      approaches and molecular diagnosis. METHODS: Here, we report a metabonomics
      profiling of tissue samples on a large cohort of human rectal cancer subjects (n
      = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR)
      based metabonomics assay, which is a highly sensitive and non-destructive method
      for the biomarker identification in biological systems. Principal component
      analysis (PCA), partial least squares discriminant analysis (PLS-DA) and
      orthogonal projection to latent structure with discriminant analysis (OPLS-DA)
      were applied to analyze the 1H-NMR profiling data to identify the distinguishing
      metabolites of rectal cancer. RESULTS: Excellent separation was obtained and
      distinguishing metabolites were observed among the different stages of rectal
      cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18)
      and normal controls. A total of 38 differential metabolites were identified, 16
      of which were closely correlated with the stage of rectal cancer. The up
      regulation of 10 metabolites, including lactate, threonine, acetate, glutathione,
      uracil, succinate, serine, formate, lysine and tyrosine, were detected in the
      cancer tissues. On the other hand, 6 metabolites, including myo-inositol,
      taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in
      cancer tissues. These modified metabolites revealed disturbance of energy, amino
      acids, ketone body and choline metabolism, which may be correlated with the
      progression of human rectal cancer. CONCLUSION: Our findings firstly identify the
      distinguishing metabolites in different stages of rectal cancer tissues,
      indicating possibility of the attribution of metabolites disturbance to the
      progression of rectal cancer. The altered metabolites may be as potential
      biomarkers, which would provide a promising molecular diagnostic approach for
      clinical diagnosis of human rectal cancer. The role and underlying mechanism of
      metabolites in rectal cancer progression are worth being further investigated.

PMID- 24138802
TI  - Are the basal cells of the mammalian epididymis still an enigma?
AB  - Basal cells are present in the columnar pseudostratified epithelium covering the
      epididymis of all mammalian species, which regulates the microenvironment where
      the functionally incompetent germ cells produced by the testis are matured and
      stored. Striking novelties have come from investigations on epididymal basal
      cells in the past 30-40 years. In addition to an earlier hypothesised scavenger
      role for basal cells, linked to their proven extratubular origin and the
      expression of macrophage antigens, basal cells have been shown to be involved in
      cell-cell cross-talk, as well as functioning as luminal sensors to regulate the
      activity of principal and clear cells. Involvement of basal cells in the
      regulation of electrolyte and water transport by principal cells was
      hypothesised. This control is suggested to be mediated by the local formation of
      prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family
      (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal
      cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of
      the epididymis to the lumen in relation to sperm maturation may be mediated by
      AQP. Most probably basal cells collaborate to the building up of the blood
      epididymis barrier through cell adhesion molecules, implying an involvement in
      immune control exerted towards sperm cells, which are foreigners in the
      environment in which they were produced. 

PMID- 24138803
TI  - Anti-inflammatory effects in muscle injury by transdermal application of gel with
      Lychnophora pinaster aerial parts using phonophoresis in rats.
AB  - BACKGROUND: Lycnophora pinaster is used by the traditional Brazilian medicine for
      the treatment of inflammations. Anti-inflammatory activity of Lycnophora pinaster
      was investigated for extracts, fractions, and isolated compounds of their aerial
      parts. The hexane extract (HE) provided alpha-amyrin, lupeol, mixture of alpha
      amyrin and lupeol, mixture of 3-O-acetyl-lupeol and 3-O-acetyl
      pseudotaraxasterol, and mixture of the steroids stigmasterol and sitosterol. The
      aqueous extract (WE) provided a fraction containing alkaloids (AF) and another
      one containing phenolic compounds (PF). METHODS: The crude hexane extract
      obtained from aerial parts of L. pinaster was submitted to chromatographic
      fractionation. The fractionation of PF was performed by preparative HPLC
      analysis, providing the flavonoid quercetin. The extracts, fractions, and
      compounds isolated from L. pinaster were tested to evaluate the anti-inflammatory
      activity by experimental model of impact injury, followed by transdermal
      application of gels with these samples. The application of the gels was performed
      using phonophoresis in rat paws after induction of muscle injury. Histological
      analysis was based on scores assigned by the capacity of decreasing the lesion.
      RESULTS: HE and WE exhibited anti-inflammatory activity. Some fractions,
      triterpenes, and steroids also reduced the inflammatory infiltrates caused by
      muscle injury. Lupeol promoted a significant reduction of inflammation. Quercetin
      also provided significant results, promoting the greatest decreases in muscle
      injury. CONCLUSION: The results of this work suggest that topical application of
      triterpenes, steroids and flavonoid significantly decreases the inflammatory
      process generated by muscle injury. The transdermal application using
      phonophoresis in rat paws of gel with lupeol and quercetin attenuates the
      inflammation.

PMID- 24138804
TI  - Hallux valgus and plantar pressure loading: the Framingham foot study.
AB  - BACKGROUND: Hallux valgus (HV), a common structural foot deformity, can cause
      foot pain and lead to limited mobility. The purpose of this study was to evaluate
      differences in plantar pressure and force during gait by HV status in a large
      population-based cohort of men and women. METHODS: A trained examiner performed a
      validated physical examination on participants' feet and recorded the presence of
      hallux valgus and other specific foot disorders. Each foot was classified into
      one of four mutually exclusive groups based on the foot examination. Foot groups
      were: (i) HV only, (ii) HV and at least one additional foot disorder (FD), (iii)
      no HV but at least one other FD, and (iv) neither HV nor FD (referent).
      Biomechanical data for both feet were collected using Tekscan Matscan. Foot
      posture during quiet standing, using modified arch index (MAI), and foot function
      during gait, using center of pressure excursion index (CPEI), were calculated per
      foot. Further, walking scans were masked into eight sub-regions using Novel
      Automask, and peak pressure and maximum force exerted in each region were
      calculated. RESULTS: There were 3205 participants, contributing 6393 feet with
      complete foot exam data and valid biomechanical measurements. Participants with
      HV had lower hallucal loading and higher forces at lesser toes as well as higher
      MAI and lower CPEI values compared to the referent. Participants with HV and
      other FDs were also noted to have aberrant rearfoot forces and pressures.
      CONCLUSIONS: These results suggest that HV alters foot loading patterns and
      pressure profiles. Future work should investigate how these changes affect the
      risk of other foot and lower extremity ailments.

PMID- 24138805
TI  - Primary prevention of overweight in preschool children, the BeeBOFT study
      (breastfeeding, breakfast daily, outside playing, few sweet drinks, less TV
      viewing): design of a cluster randomized controlled trial.
AB  - BACKGROUND: Two overweight prevention interventions were developed to be offered
      by preventive Youth Health Care (YHC) in addition to the currently applied
      overweight prevention protocol to parents of 0-3 year old children. The two
      interventions aim to support parents of preschool children to realize healthy
      child nutrition and activity behaviors of their young child. The aim of this
      study is to assess the effects of the two overweight prevention interventions
      with regard to child health behaviors and child Body Mass Index. METHODS/DESIGN:
      A cluster randomized controlled trial was conducted among parents and their
      preschool children who attend one of 51 participating YHC teams. The teams were
      randomly allocated to one of the two intervention groups, or to the control group
      (care as usual).The 'BBOFT+' intervention focuses on effective child rearing by
      parents from birth onwards by enlarging parental skills concerning healthy
      behavioural life-style habits. Parents who are allocated to the 'E-health4Uth
      Healthy toddler' intervention group, at the child age of circa 18 and 24 months
      old, are invited to complete an online E-health module providing tailored health
      education regarding healthy child nutrition and activity behaviors. The E-health
      messages are discussed and reinforced during the subsequent regularly scheduled
      visits by YHC professionals, and were repeated after 4 weeks.The primary outcome
      measures at child age 3 years are: overweight inducing/reducing behaviors, (for
      'BBOFT+' only) healthy sleep, Body Mass Index and prevalence of overweight and
      obesity. Secondary outcome measures are attitudes and other cognitive
      characteristics of the parents regarding the overweight-related behaviors of
      their child, parenting styles and practices, and health-related quality of life
      of the children. DISCUSSION: We hypothesize that the use of the additional
      interventions will result in a healthier lifestyle of preschool children and an
      improved BMI and less development of overweight and obesity compared to usual
      care. TRIAL REGISTRATION: Nederlands Trial Register NTR1831.

PMID- 24138806
TI  - Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and
      differentiation of human colorectal Caco-2 cell.
AB  - BACKGROUND: Human colon adenocarcinoma cells are resistant to chemotherapeutic
      agents, such as anthracyclines, that induce death by increasing the reactive
      oxygen species. A number of studies have been focused on chemo-preventive use of
      resveratrol as antioxidant against cardiovascular diseases, aging and cancer.
      While resveratrol cytotoxic action was due to its pro-oxidant properties. In this
      study, we investigate whether the Resveratrol (trans-3,5,49-trihydroxystilbene)
      and its natural precursor Polydatin (resveratrol-3-O-b-mono-D-glucoside, the
      glycoside form of resveratrol) combination, might have a cooperative antitumor
      effect on either growing or differentiated human adenocarcinoma colon cancer
      cells. METHODS: The polydatin and resveratrol pharmacological interaction was
      evaluated in vitro on growing and differentiated Caco-2 cell lines by median drug
      effect analysis calculating a combination index with CalcuSyn software. We have
      selected a synergistic combination and we have evaluated its effect on the
      biological and molecular mechanisms of cell death. RESULTS: Simultaneous exposure
      to polydatin and resveratrol produced synergistic antiproliferative effects
      compared with single compound treatment. We demonstrated that polydatin alone or
      in combination with resveratrol at 3:1 molar ratio synergistically modulated
      oxidative stress, cell cycle, differentiation and apoptosis. Worthy of note
      treatment with polydatin induced a nuclear localization and decreased expression
      of heat shock protein 27, and vimentin redistributed within the cell.
      CONCLUSIONS: From morphological, and biochemical outcome we obtained evidences
      that polydatin induced a transition from a proliferative morphology to cell
      specific differentiated structures and caused human CaCo-2 cell death by
      induction of apoptosis. Our data suggest the potential use of polydatin in
      combination chemotherapy for human colon cancer.

PMID- 24138807
TI  - Human dose response relation for airborne exposure to Coxiella burnetii.
AB  - BACKGROUND: The recent outbreak of Q fever in the Netherlands between 2007 and
      2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may
      cause Q fever but the size of the population exposed during the outbreak remained
      uncertain as little is known of the infectivity of this pathogen. The
      quantification of the infectiousness and the corresponding response is necessary
      for assessing the risk to the population. METHODS: A human challenge study was
      published in the 1950s but this study quantified the dose of C. burnetii in
      relative units. Data from a concurrent guinea pig challenge study were combined
      with a recent study in which guinea pigs were challenged with a similar aerosol
      route to quantify human exposure. Concentration estimates for C. burnetii are
      made jointly with estimates of the dose response parameters in a hierarchical
      Bayesian framework. RESULTS: The dose for 50% infection (InfD50%) in human
      subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for
      50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The
      probability of a single viable C. burnetii causing infection in humans is 0.44
      (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55). CONCLUSIONS: To our
      knowledge this is the first human dose-response model for C. burnetii. The
      estimated dose response relation demonstrates high infectivity in humans. In many
      published papers the proportion of infected individuals developing illness is
      reported to be 40%. Our model shows that the proportion of symptomatic infections
      may vary with the exposure dose. This implies that presence of these bacteria in
      the environment, even in small numbers, poses a serious health risk to the
      population.

PMID- 24138808
TI  - Patient reported facial scar assessment: directions for the professional.
AB  - BACKGROUND: The face is central to our identity and provides our most expressive
      means of communication. Currently, the role of facial scarring in relation to
      self-esteem is unclear and the value of self-reported scar assessment is
      insufficiently understood. The aim of this study was twofold: (1) to assess the
      extent of agreement between patients' ratings and observers' ratings of facial
      scar characteristics; and (2) to examine if patients' and observers' scar
      characteristics ratings, or the differences, are associated with the patients'
      self-esteem. METHODS: A prospective study was conducted including patients with
      facial burns. Patients completed the Patient and Observer Scar Assessment Scale
      (POSAS) and the Rosenberg Self-Esteem Scale 3 months post-burn. RESULTS: Ninety
      four subjects were included, 76 (81%) men and mean percentage TBSA burned was
      12.4 (SD 10.4; range 1-50). Subject's and observer's assessment were
      significantly positively correlated and were identical in 53% of the cases.
      Subjects' assessments and discrepancy scores on the scar characteristic surface
      roughness were associated with self-esteem in multiple regression analysis.
      CONCLUSIONS: The majority of the patients scored the quality of facial scars in a
      similar way as the professionals. Furthermore, facial scarring appeared only
      moderately associated with self-esteem. However, our study suggests that using
      both patients' and professionals' scar assessments provides more useful
      information regarding the patients' well-being relative to focussing on the
      separate assessments only. In particular a discrepancy between the patients' and
      professionals' view on surface roughness might be an early indication of
      psychological difficulties and a call for further clinical attention.

PMID- 24138809
TI  - Temporizing surgical management improves outcome in patients with Vibrio
      necrotizing fasciitis complicated with septic shock on admission.
AB  - BACKGROUND: Necrotizing fasciitis (NF) caused by Vibrio infection is one of the
      most fatal diseases, resulting in high morbidity and mortality. Early diagnosis
      and effective surgical intervention are the mainstays for better outcomes for
      affected patients. Currently, standard surgical management calls for prompt and
      aggressive debridement and amputation. However, due to its rapid progression and
      deterioration, 50-60% of Vibrio NF cases present with septic shock and multiple
      organ dysfunction on admission. These patients, who usually have many surgical
      contraindications, are unable to tolerate a prolonged aggressive surgical
      debridement. Therefore, determining the optimal surgical intervention for these
      particularly severe patients remains a formidable problem in emergency medicine.
      METHODS: A retrospective study was conducted on patients who underwent surgery
      for Vibrio NF and septic shock on admission to the emergency room from April 2001
      to October 2012. These patients received the same treatment protocol, with the
      exception of the initial surgical intervention strategy. Nineteen patients were
      treated with a temporizing strategy, which called for simple incisions and
      drainage under regional anesthesia, followed by complete debridement 24h later.
      Another fifteen patients underwent aggressive surgical debridement during the
      first operative procedure. Basic demographics, laboratory results on admission,
      clinical course and outcomes were compared to assess the efficacy and safety of
      two initial surgical treatment methods: the temporizing strategy and the
      aggressive strategy. RESULTS: Thirty-four patients were included in this study,
      and the average age was 51.65 years. Chronic liver disease was the most prevalent
      preexisting condition (50.00%) and the lower limbs were most commonly involved in
      infection (76.47%). In this patient population, 19 cases underwent surgery with a
      temporizing therapeutic strategy, while the remaining 15 cases were treated with
      an aggressive surgical strategy. There were no differences between the two groups
      with respect to demographics, severity of illness and laboratory data. Compared
      with those treated with the aggressive strategy, patients treated with the
      temporizing strategy had shorter operation time (40.79 +/- 16.61 vs. 102.00 +/-
      18.97 min, p<0.001), less bleeding (120.53 +/- 67.20 vs. 417.33 +/- 134.72 mL,
      p<0.001), a reduced amount of intraoperatively administrated fluid (3144.70 +/-
      554.71 vs. 1637.40 +/- 302.11 mL, p<0.001), decreased maximum dose of dopamine
      (15.73 +/- 5.64 vs. 10.47 +/- 5.61 MUg/kg/min, p=0.011) and noradrenaline (20.13
      +/- 7.50 vs. 13.37 +/- 6.18 MUg/kg/min, p=0.007), lower arterial lactate values
      at the end of surgery (5.56+/-1.99 vs. 8.66 +/- 3.25 mmol/L, p=0.004), and, most
      importantly, lower mortality (26.32% vs. 60.00%, p=0.048). All other treatment
      conditions, such as duration of vasopressor therapy, number of debridement
      procedures, rate of amputation, ICU length of stay and hospital length of stay,
      were the same for both groups. CONCLUSION: The temporizing strategy, with early
      initiation of simple incisions and drainage under regional anesthesia followed by
      complete debridement 24h later, is more feasible and effective for patients with
      Vibrio NF complicated with septic shock, as compared with the aggressive surgical
      debridement strategy.

PMID- 24138810
TI  - Evaluation of farmers' diagnostic performance for detection of diarrhoea in
      nursery pigs using digital pictures of faecal pools.
AB  - BACKGROUND: Over-consumption of antibiotics in the pig industry is of concern in
      relation to antimicrobial resistance. False positive disease diagnosis may result
      in the treatment of healthy animals. In Denmark, diarrhoea is the most common
      cause of antibiotic treatment in pigs. Farm personnel are not professional
      clinicians, which could result in inappropriate antibiotic treatments of
      diarrhoea.The primary objectives of this pilot study using digital pictures of
      faecal pools was to evaluate farmers' diagnostic performance in the assessment of
      faecal consistency in nursery pigs and to investigate the effect of different co
      variables, including practical experience. A secondary objective was to compare
      the diagnostic performance of farmers with that of veterinarians.At a pig
      congress, observers (farm personnel and veterinarians) working professionally
      with pigs participated in a faecal consistency test consisting of 16 pictures of
      faecal pools (eight diarrhoeic and eight non-diarrhoeic). The faecal pools had
      previously been collected and subjected to faecal dry matter determination. The
      true status of the faecal pools was determined by the faecal dry matter content
      (diarrhoea: faecal dry matter <= 18%). The true status was used to evaluate the
      farmers' and veterinarians' diagnostic performance. RESULTS: A total of 119
      farmers and 18 veterinarians were included in the statistical analysis. For the
      farmers, the mean proportion of faecal pools assessed as diarrhoeic was 0.48, the
      mean proportion of correctly classified faecal pools was 0.84, the mean
      diagnostic sensitivity was 0.83 and the mean diagnostic specificity was 0.86.
      Farmers with less than four years of practical experience detected clinical
      diarrhoea more accurately than farmers with more than four years of practical
      experience (p < 0.05). No significantly differences between farmers and
      veterinarians was observed (p > 0.20). CONCLUSIONS: The results, using digital
      pictures of faecal pools, suggest that farmers and veterinarians have similar
      diagnostic performance in relation to diarrhoea. False positive classification of
      non-diarrhoeic pigs appears to be a larger problem than false negative
      classification of diarrhoeic pigs under Danish conditions. If these results can
      be confirmed under practical conditions, training in, and validation of, clinical
      diagnoses may be an important factor in reducing antibiotic consumption in the
      pig industry.

PMID- 24138811
TI  - The relationship between lymphatic vascular density and vascular endothelial
      growth factor A (VEGF-A) expression with clinical-pathological features and
      survival in pancreatic adenocarcinomas.
AB  - BACKGROUND: Pancreatic cancer is a rare tumor with an extremely low survival
      rate. Its known risk factors include the chronic use of tobacco and excessive
      alcohol consumption and the presence of chronic inflammatory diseases, such as
      pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have
      been the focus of recent research, are considered prognostic factors for cancer
      development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may
      provide new insights for designing treatments according to the different
      properties of the tumor. The aim of this study was to evaluate the density of
      blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic
      adenocarcinomas, as well as the relationship between blood and lymphatic vascular
      density and the prognostically important clinical-pathological features of
      pancreatic tumors. METHODS: Paraffin blocks containing tumor samples from 100
      patients who were diagnosed with pancreatic cancer between 1990 and 2010 were
      used to construct a tissue microarray. VEGF expression was assessed in these
      samples by immunohistochemistry. To assess the lymphatic and vascular properties
      of the tumors, 63 cases that contained sufficient material were sectioned
      routinely. The sections were then stained with the D2-40 antibody to identify the
      lymphatic vessels and with a CD34 antibody to identify the blood vessels. The
      vessels were counted individually with the Leica Application Suite v4 program.
      All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA)
      software, and p values <= 0.05 were considered significant. RESULTS: In the Cox
      regression analysis, advanced age (p=0.03) and a history of type 2 diabetes
      (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors
      for pancreatic cancer. Blood vessel density (BVD) had no relationship with
      clinical-pathological features or death. Lymphatic vessel density (LVD) was
      inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis,
      we found a significant association between low LVD (p=0.021), VEGF expression
      (p=0.023) and low patient survival. CONCLUSIONS: Pancreatic carcinogenesis is
      related to a history of chronic inflammatory processes, such as type 2 diabetes
      and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can
      be considered an early event that enables the dissemination of metastases. VEGF
      expression and low LVD can be considered as poor prognostic factors as tumors
      with this profile are fast growing and highly aggressive. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514.

PMID- 24138812
TI  - Hemophilia B Leyden and once mysterious cis-regulatory mutations.
AB  - Hemophilia B is a classic, monogenic blood clotting disease caused by mutations
      in the coagulation factor IX (F9) locus. Although interpreting mutations within
      the gene itself has been relatively straightforward, ascribing molecular
      mechanisms to the complete suite of mutations within the promoter region has
      proven somewhat difficult and has only recently been achieved. These mutations,
      which are clustered at discrete transcription factor binding sites, dynamically
      alter the developmental expression of F9 in different ways. They illustrate how
      single-nucleotide mutations in cis-regulatory regions can have drastic
      ramifications for the control of gene expression and in some instances be
      causative of disease. Here we present the human F9 promoter as a model example
      for which saturation mutation mapping has revealed the mechanisms of its
      regulation. Moreover, we suggest that the growing number of genome-wide studies
      of transcription factor activity will accelerate both the discovery and
      understanding of regulatory polymorphisms and mutations. 

PMID- 24138813
TI  - CAFA and the open world of protein function predictions.

PMID- 24138814
TI  - The risk of childhood autism among second-generation migrants in Finland: a case
      control study.
AB  - BACKGROUND: Studying second-generation immigrants can help in identifying genetic
      or environmental risk factors for childhood autism. Most previous studies have
      focused on maternal region of birth and showed inconsistent results. No previous
      study has been conducted in Finland. METHODS: The study was a nested case-control
      study based on a national birth cohort. Children born in 1987-2005 and diagnosed
      with childhood autism by the year 2007 were identified from the Finnish Hospital
      Discharge Register. Controls were selected from the Finnish Medical Birth
      Register. Information on maternal and paternal country of birth and mother tongue
      was collected from the Finnish Central Population Register. There were 1132 cases
      and 4515 matched controls. The statistical test used was conditional logistic
      regression analysis. RESULTS: Compared with children with two Finnish parents,
      the risk of childhood autism was increased for those whose parents are both
      immigrants (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.2-2.7)
      and for those with only an immigrant mother (aOR 1.8, 95% CI 1.2-2.7), but not
      for those with only an immigrant father. The risk was increased for those with a
      mother born in the former Soviet Union or Yugoslavia and for those with a mother
      or a father born in Asia. Specific parental countries of birth associated with an
      increased risk were the former Soviet Union, the former Yugoslavia and Vietnam.
      CONCLUSIONS: In Finland, children who are born to immigrant mothers with or
      without an immigrant partner, have an increased risk of childhood autism. The
      risk varies with immigrant parents' region of birth. The findings may help in
      identifying possible risk factors, which can be examined in future studies.

PMID- 24138815
TI  - Inhibition of Raf-MEK-ERK and hypoxia pathways by Phyllanthus prevents metastasis
      in human lung (A549) cancer cell line.
AB  - BACKGROUND: Lung cancer constitutes one of the malignancies with the greatest
      incidence and mortality rates with 1.6 million new cases and 1.4 million deaths
      each year. Prognosis remains poor due to deleterious development of multidrug
      resistance resulting in less than 15% lung cancer patients reaching five years
      survival. We have previously shown that Phyllanthus induced apoptosis in
      conjunction with its antimetastastic action. In the current study, we aimed to
      determine the signaling pathways utilized by Phyllanthus to exert its
      antimetastatic activities. METHODS: Cancer 10-pathway reporter array was
      performed to screen the pathways affected by Phyllanthus in lung carcinoma cell
      line (A549) to exert its antimetastatic effects. Results from this array were
      then confirmed with western blotting, cell cycle analysis, zymography technique,
      and cell based ELISA assay for human total iNOS. Two-dimensional gel
      electrophoresis was subsequently carried out to study the differential protein
      expressions in A549 after treatment with Phyllanthus. RESULTS: Phyllanthus was
      observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via
      suppression of Raf protein. Inhibition of this pathway resulted in the
      suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis.
      Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1alpha that led
      to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of
      proteins downregulated by Phyllanthus that were involved in metastatic processes,
      including invasion and mobility proteins (cytoskeletal proteins), transcriptional
      proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic
      protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species
      tested, P. urinaria showed the greatest antimetastatic activity. CONCLUSIONS:
      Phyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways
      that led to suppression of various critical proteins for A549 invasion and
      migration.

PMID- 24138816
TI  - An overview of cardiac morphogenesis.
AB  - Accurate knowledge of normal cardiac development is essential for properly
      understanding the morphogenesis of congenital cardiac malformations that
      represent the most common congenital anomaly in newborns. The heart is the first
      organ to function during embryonic development and is fully formed at 8 weeks of
      gestation. Recent studies stemming from molecular genetics have allowed
      specification of the role of cellular precursors in the field of heart
      development. In this article we review the different steps of heart development,
      focusing on the processes of alignment and septation. We also show, as often as
      possible, the links between abnormalities of cardiac development and the main
      congenital heart defects. The development of animal models has permitted the
      unraveling of many mechanisms that potentially lead to cardiac malformations. A
      next step towards a better knowledge of cardiac development could be multiscale
      cardiac modelling.

PMID- 24138817
TI  - Role of calcium desensitization in the treatment of myocardial dysfunction after
      deep hypothermic circulatory arrest.
AB  - INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces
      calcium desensitization by troponin I (cTnI) phosphorylation which results in
      myocardial dysfunction. This study investigated the acute overall hemodynamic and
      metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on
      myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats
      (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation
      and were cooled to a core temperature of 13 degrees C to 15 degrees C within 30
      minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats
      were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2
      MUg/kg/min; n = 15), epinephrine (0.1 MUg/kg/min; n = 15) or saline (control; n =
      10). Systolic and diastolic functions were evaluated at different preloads with a
      conductance catheter. RESULTS: The slope of left ventricular end-systolic
      pressure volume relationship (Ees) and preload recruitable stroke work (PRSW)
      recovered significantly better with levosimendan compared to epinephrine (Ees: 85
      +/- 9% vs 51 +/- 11%, P<0.003 and PRSW: 78 +/- 5% vs 48 +/- 8%, P<0.005;
      baseline: 100%). Levosimendan but not epinephrine reduced left ventricular
      stiffness shown by the end-diastolic pressure-volume relationship and improved
      ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as
      well as energy charge and reduced plasma lactate concentrations. In normothermia
      experiments epinephrine in contrast to Levosimendan increased cTnI
      phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation
      increased 4.5-fold in the saline and epinephrine group compared to normothermia
      but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to
      prevention of calcium desensitization by cTnI phosphorylation is more effective
      than epinephrine for treatment of myocardial dysfunction after rewarming from
      DHCA.

PMID- 24138818
TI  - Challenges and advances towards the rational design of mRNA vaccines.
AB  - In recent years, mRNA vaccines have emerged as a safe and potent approach for the
      induction of cellular immune responses. Whereas initial studies were limited to
      the ex vivo loading of dendritic cells (DCs) with antigen-encoding mRNA, recent
      progress has led to the development of improved mRNA vaccines that enable direct
      in vivo targeting of DCs. Although preclinical studies demonstrated their potency
      in inducing antitumor immunity, several bottlenecks hinder the broader
      application of mRNA vaccines. In this review, we discuss the challenges
      associated with mRNA-based vaccination strategies, the technological advances
      that have been made to overcome these limitations, and the hurdles that remain to
      be tackled for the development of an optimal mRNA vaccine. 

PMID- 24138819
TI  - Eriosema chinense: a rich source of antimicrobial and antioxidant flavonoids.
AB  - Six prenylated flavonoids, (2R,3S)-3,5,4'-trihydroxy-6"
      6"dimethylpyrano(2",3":7,6)-8-(3"', 3"'-dimethylallyl)flavanone, (2R,3S)-3,5,2'
      trihydroxy-4'-methoxy-6",6"-dimethylpyrano(2",3":7,6)-8-(3"',3"'
      dimethylallyl)flavanone, (2R,3R)-3,5,2',4'-tetrahydroxy-6",6"
      dimethylpyrano(2",3":7,6)-8-(3"',3"'-dimethylallyl)flavanone, 3,5,2',4'
      tetrahydroxy-6",6"-dimethylpyrano(2",3":7,6)-8-(3"',3"'-dimethylallyl)flavone,
      (2R,3R,2"'R)-3,5,2"'-trihydroxy-4'-methoxy-6",6"-dimethylpyrano(2",3":7,6)-8-(3"'
      methylbut-3"'-enyl)flavanone, (2R,3R)-3,5-dihydroxy-4'-methoxy-6",6"
      dimethylpyrano(2",3":7,6)-8-(2"',3"'-epoxy-3"'-methyl butyl)flavanone, an
      isoflavone, 6,7-dimethoxy-5,2',4'-trihydroxyisoflavone, and octaeicosanyl-trans-p
      coumarate together with 12 known compounds, were isolated from roots of Eriosema
      chinense. This structural elucidation was determined by spectroscopic methods.
      Several isolates and derivatives were evaluated for their antimicrobial and
      antioxidant activities. Results obtained provide additional evidence showing that
      the presence of both the free phenolic OH and the lipophilic prenyl groups are
      crucial for potent antimicrobial activity against yeast, gram positive and gram
      negative bacteria, whereas the presence of free phenolic OH group is required for
      strong radical scavenging property. 

PMID- 24138820
TI  - Experience with the Coonrad-Morrey total elbow arthroplasty: 78 consecutive total
      elbow arthroplasties reviewed with an average 5 years of follow-up.
AB  - BACKGROUND: The Coonrad-Morrey total elbow arthroplasty is a linked implant. This
      study investigated the hypotheses that reliable results can be obtained in
      rheumatoid patients and in traumatic conditions and that the survival rate is
      similar to or better than what has been published for nonlinked implants.
      METHODS: Surgery was performed on 70 consecutive patients (78 elbows) for an
      inflammatory arthritis (45 elbows) or a traumatic condition (33 elbows: 18 acute
      fractures of the distal humerus, 10 nonunions, and 5 post-traumatic arthritis).
      RESULTS: At an average of 5 years of follow-up (2 to 11 years), the mean Mayo
      Elbow Performance Score for the group that had inflammatory arthritis (89 +/- 13
      points) was significantly higher than that for the group with a traumatic
      condition (80 +/- 17 points). The QuickDASH score was not significantly different
      according to the etiology. Radiolucencies were observed in 17 cases around the
      humeral component and in 14 cases around the ulnar component. Bushing wear was
      observed in 14 cases. There were 27 complications, and 9 of them went to a
      revision procedure. The survival rate was 97.7% at 5 years and 91.0% at 10 years
      if we consider revision for aseptic loosening as an endpoint. CONCLUSIONS: The
      Coonrad-Morrey total elbow arthroplasty allows treatment of a large spectrum of
      causes with satisfactory results. Better results have been obtained for
      rheumatoid patients than for patients with trauma. The rate of complication
      remains high even if the rate of implant revision stays low. However, the
      increased incidence of lucent lines around the ulnar component with follow-up and
      bushing wear are of concern.

PMID- 24138821
TI  - Radiotherapy for prevention of heterotopic ossification of the elbow: a
      systematic review of the literature.
AB  - BACKGROUND: Heterotopic ossification is a pathological process characterized by
      abnormal formation of bone in nonskeletal tissue. Radiotherapy for heterotopic
      ossification of the elbow is questionable because of possible adverse effects.
      METHODS: A systematic review of the literature was conducted in MEDLINE, Scopus,
      ISI Web of Science, National Institute for Health and Clinical Excellence,
      National Guideline Clearinghouse, System for Information on Grey Literature in
      Europe, ClinicalTrials.gov, Cochrane Central Register of Clinical Trials, and
      Cochrane Database of Systematic Reviews up to April 2012. All published articles
      assessing interventions including radiotherapy for prevention of heterotopic
      ossification in the elbow of adult patients were considered. Information was
      recorded by the first two authors, and disagreements in interpretation were
      resolved by consensus. RESULTS: In total, 27 studies using radiotherapy for elbow
      heterotopic ossification were identified (1 randomized clinical trial, 1 case
      control study, and 25 case reports and case series) in the literature. Most of
      them used a single dose of 7.0 Gy. The randomized clinical trial was stopped
      early because of severe adverse effects (pseudarthrosis) caused by radiation. The
      case-control study showed that radiotherapy did not effectively prevent
      recurrence of heterotopic ossification. The case reports and case series
      mentioned only sparse adverse events. CONCLUSION: The use of radiation therapy
      for prevention of heterotopic ossification of the elbow is supported by weak
      evidence.

PMID- 24138822
TI  - Traumatic extrusion of 13-cm segment of humerus and complete transection of ulnar
      nerve treated with vascularized fibular graft and acute nerve repair: case
      report.

PMID- 24138823
TI  - Severe hypoglycemia in pregnant women with type 2 diabetes-A relevant clinical
      problem.

PMID- 24138824
TI  - Lgr5 promotes cancer stemness and confers chemoresistance through ABCB1 in
      colorectal cancer.
AB  - INTRODUCTION: Chemotherapy failure is a major problem in patients with advanced
      colorectal carcinoma (CRC). Leucine-rich repeat-containing G-protein-coupled
      receptor 5 (Lgr5) is a well-established target gene of the Wnt pathway and is a
      bona fide marker of CRC cancer stem cells (CSCs). Our previous study showed that
      CRC patients with higher Lgr5 level are associated with poor response to 5
      fluoracil-based treatment. In this study, we investigated the mechanisms
      underlying Lgr5-associated chemoresistance in cancer stem cells derived from
      cultured CRC cells. MATERIALS AND METHODS: Cancer stem cells were isolated from
      CRC cell lines by spheroid culture. The effect of Lgr5 on CRC cancer stem cell
      was investigated using both gain- and loss-of-function approaches. Stemness
      property was evaluated using sphere formation assay, side population analysis,
      and stem cell marker expression. Lgr5 and ABCB1 expression in CRC tissues was
      determined using immunohistochemical staining. RESULTS: Forced expression of Lgr5
      increased the CRC sphere-forming efficiency and spheroid size while depletion of
      Lgr5 reduced the stem cell property in cultured CRC cells. Over-expression of
      Lgr5 also reduced the sensitivity of cultured CRC cells, including adherent and
      spheroids, towards 5-fluoracil and oxalipatin. In addition, Lgr5 positively
      regulates the expression of ABCB1 in both adherent and spheroid CRC cells.
      Finally, in human CRC tissues, higher expression levels of Lgr5 were associated
      with higher ABCB1 expression. CONCLUSIONS: The present study demonstrated that
      Lgr5 plays an active role in promoting the cancer stem cell property and that
      Lgr5 confers chemoresistance to CRC cells via ABCB1 induction.

PMID- 24138825
TI  - Association between health examination items and body mass index among school
      children in Hualien, Taiwan.
AB  - BACKGROUND: To assess the prevalence of obesity and major physical examination
      items including dental caries, myopia, pinworm, hematuria, and proteinuria among
      school children in Hualien, Taiwan. In addition, the health status differences
      between gender, grader, levels of residence urbanization, and body mass index
      (BMI) were examined. METHODS: Cross-sectional studies with a total of 11,080
      students (age, 7-14 years) in grades 1, 4, and 7 were evaluated for weight,
      height, routine physical examination, and urine analysis during the 2010 Student
      Health Examination in Hualien. Frequencies, Chi-square test, and logistic
      regression were conducted using SPSS. RESULTS: Of the 11,080 students evaluated,
      1357 (12.2%) were overweight, and 1421 (12.8%) were obese. There were significant
      differences in overweight/obese prevalence by gender, by grader, and by levels of
      residence urbanization. Dental caries, myopia, and obesity were the most
      prevalent health problems among these students (75.6%, 33.0%, and 12.8%,
      respectively). In crude and adjusted analyses, research results showed that there
      were significant differences in the prevalence of major physical examination
      items between different gender, grader, levels of residence urbanization, and BMI
      groups. Girls had a higher prevalence of dental caries, myopia, and hematuria
      than boys (all p < 0.01), whereas boys had a higher prevalence of pinworm than
      girls (p = 0.02). Students in higher grades had significantly higher prevalence
      of myopia, hematuria, and proteinuria (all p < 0.01), whereas students in lower
      grades had higher prevalence of dental caries and pinworm (p < 0.01). Students
      with abnormal BMI had lower prevalence of pinworm (p < 0.01). Students residing
      in suburban and rural areas had higher prevalence of dental caries, pinworm, and
      hematuria (all p < 0.01), and lower prevalence of myopia than students residing
      in urban areas (all p < 0.01). CONCLUSION: Routine health examination provides an
      important way to detect students' health problems. Our study elucidated major
      health problems among school children in Hualien, Taiwan. In addition, the
      results also indicated that the prevalence of health problems had a significant
      relationship with gender, grader, levels of residence urbanization, and BMI. It
      is suggested that school health interventions should consider students' health
      profiles along with their risk factors status in planning.

PMID- 24138826
TI  - Injectable thermosensitive PEG-PCL-PEG hydrogel/acellular bone matrix composite
      for bone regeneration in cranial defects.
AB  - We have certified that the injectable thermosensitive ABM/PECE composite
      presented promising potential in bone regeneration benefited from the
      incorporation of the intrinsic osteoinductive acellular bone matrix (ABM)
      granules into the poly(ethylene glycol)-poly(epsilon-capro-lactone)-poly(ethylene
      glycol) (PEG-PCL-PEG, PECE) hydrogel. In this study, the 12 mm * 8 mm * 2 mm
      cranial defects of the New Zealand white rabbits were fabricated to evaluate the
      bone regeneration effect. The ABM/PECE composite was injected into the defect
      while the pure PECE as control, and the bone regeneration was evaluated at 4, 12
      and 20 weeks post-surgery by X-radiological examination, micro-computed
      tomography examination and histological analysis. In ABM/PECE composite treated
      group, the new bone formed originally from both the margin and the center of the
      defect, and the defect region had healed up to 20 weeks. Furthermore, the shadow
      density of the newly formed bone eventually approximated to host cortical bone.
      In comparison, the control group was filled with sparing new bone with low
      density only from the periphery of the defect. Meanwhile, the quantitative
      determination of new bone by histomorphometry confirmed the excellent bone
      regeneration of ABM/PECE composite. All the results suggested that the ABM/PECE
      composite presented enhanced bone regeneration guidance in rabbit cranial
      defects.

PMID- 24138827
TI  - Differential nanotoxicological and neuroinflammatory liabilities of non-viral
      vectors for RNA interference in the central nervous system.
AB  - Progression of RNA interference-based gene silencing technologies for the
      treatment of disorders of the central nervous system (CNS) depends on the
      availability of efficient non-toxic nanocarriers. Despite advances in the field
      of nanotechnology undesired and non-specific interactions with different brain
      cell types occur and are poorly investigated. To this end, we studied the
      cytotoxic and neuroinflammatory effects of widely-used transfection reagents and
      modified amphiphilic beta-cyclodextrins (CDs). All non-viral vectors formed
      positively charged nanoparticles with distinctive physicochemical properties.
      Differential and significant cytotoxic effects were observed among commercially
      available cationic vectors, whereas CDs induced limited disruptions of cellular
      membrane integrity and mitochondrial dehydrogenase activity. Interestingly,
      murine derived BV2 microglia cells and a rat striatal in vitro model of
      Huntington's disease (ST14A-HTT120Q) were more susceptible to toxicity than human
      U87 astroglioma cells. BV2 microglia presented significant increases in cytokine,
      toll-like receptor 2 and cyclooxygenase-2 gene expression after transfection with
      selected commercial vectors but not with CD.siRNA nanoparticles. Non-viral siRNA
      nanoparticles formulated with G6 polyamidoamine (PAMAM) also significantly
      increased cytokine gene expression in the brain following injections into the
      mouse striatum. Together our data identify modified CDs as nanosystems that
      enable siRNA delivery to the brain with low levels of cytotoxicity and
      immunological activation.

PMID- 24138828
TI  - Overcoming disease-induced growth factor resistance in therapeutic angiogenesis
      using recombinant co-receptors delivered by a liposomal system.
AB  - Current treatment options for ischemia include percutaneous interventions,
      surgical bypass or pharmacological interventions aimed at slowing the progression
      of vascular disease. Unfortunately, while each of these treatment modalities
      provides some benefit for patients in the short-term, many patients have
      resistant or recurrent disease that is poorly managed by these therapies. A
      highly appealing strategy for treating ischemic disease is to stimulate the
      revascularization of the tissue to restore blood flow. While many techniques have
      been explored in this regard, clinically effective angiogenic therapies remain
      elusive. Here, we hypothesized that the presence of co-morbid disease states
      inherently alters the ability of the body to respond to angiogenic therapies.
      Using a mouse model of diabetes and obesity, we examined alterations in the major
      components for the signaling pathways for FGF-2, VEGF-A and PDGF under normal and
      high fat dietary conditions. In skeletal muscle, a high fat diet increased levels
      of growth factor receptors and co-receptors including syndecan-1, syndecan-4 and
      PDGFR-alpha in wild-type mice. These increases did not occur in Ob/Ob mice on a
      high fat diet and there was a significant decrease in protein levels for
      neuropilin-1 and heparanase in these mice. With the aim of increasing growth
      factor effectiveness in the context of disease, we examined whether local
      treatment with alginate gel-delivered FGF-2 and syndecan-4 proteoliposomes could
      overcome the growth factor resistance in these mice. This treatment enhanced the
      formation of new blood vessels in Ob/Ob mice by 6 fold in comparison to FGF-2
      delivered alone. Our studies support that disease states cause a profound shift
      in growth factor signaling pathways and that co-receptor-based therapies have
      potential to overcome growth factor resistance in the context of disease. 

PMID- 24138829
TI  - An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography.
AB  - An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2"-(10-(3
      (5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10
      tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor
      angiography based on its high relaxivity and long blood half-life. The
      preparation procedures of the contrast agent have been modified in order to
      achieve higher yield and improve the synthetic reproducibility. High relaxivity
      of Gd(DO3A-Lys) has been confirmed by measurements at 3 T, 7 T and 9.4 T magnetic
      fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A
      Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell
      indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mM [Gd] concentration. In
      vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues
      up to 0.2 mM [Gd]. While the toxicity on liver tissue was not observed at low
      dosage (1.0 mM [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high
      dosage (2.0 mM [Gd]). The DO3A-Lys has been labeled with (68)Ga radioisotope for
      biodistribution studies. (68)Ga(DO3A-Lys) has high uptake in both HT1080 and
      U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR
      angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that
      Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and
      displays promising characteristics of an MRI contrast agent for tumor
      angiography.

PMID- 24138830
TI  - Conductive PPY/PDLLA conduit for peripheral nerve regeneration.
AB  - The significant drawbacks and lack of success associated with current methods to
      treat critically sized nerve defects have led to increased interest in neural
      tissue engineering. Conducting polymers show great promise due to their
      electrical properties, and in the case of polypyrrole (PPY), its cell
      compatibility as well. Thus, the goal of this study is to synthesize a conducting
      composite nerve conduit with PPY and poly(d, l-lactic acid) (PDLLA), assess its
      ability to support the differentiation of rat pheochromocytoma 12 (PC12) cells in
      vitro, and determine its ability to promote nerve regeneration in vivo. Different
      amounts of PPY (5%, 10%, and 15%) are used to synthesize the conduits resulting
      in different conductivities (5.65, 10.40, and 15.56 ms/cm, respectively). When
      PC12 cells are seeded on these conduits and stimulated with 100 mV for 2 h, there
      is a marked increase in both the percentage of neurite-bearing cells and the
      median neurite length as the content of PPY increased. More importantly, when the
      PPY/PDLLA nerve conduit was used to repair a rat sciatic nerve defect it
      performed similarly to the gold standard autologous graft. These promising
      results illustrate the potential that this PPY/PDLLA conducting composite conduit
      has for neural tissue engineering.

PMID- 24138831
TI  - FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic
      colorectal cancer.
AB  - BACKGROUND: BRAF V600E mutation plays a negative prognostic role in metastatic
      colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of
      4-6months with first-line conventional treatments. Our group recently reported in
      a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5
      FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable
      results in terms of PFS and Overall Survival (OS) also in this poor-prognosis
      subgroup. The aim of this work was to prospectively validate our retrospective
      finding. PATIENTS AND METHODS: This phase II trial was designed to detect an
      increase in 6month-Progression Free Rate (6m-PFR) from 45% to 80% in a population
      of BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab.
      Secondary end-points were PFS, OS, response rate (RR) and the analysis of outcome
      parameters in the pooled population consisting of both retrospectively and
      prospectively included patients. This trial is registered with
      ClinicalTrials.gov, number NCT01437618. RESULTS: Two-hundred-fourteen potentially
      eligible mCRC patients were screened for BRAF mutational status. Fifteen BRAF
      mutant patients (7%) were included in the validation cohort. At a median follow
      up of 25.7months, 6m-PFR was 73%. Median PFS and OS were 9.2 and 24.1months,
      respectively. In the pooled population, at a median follow up of 40.4months, 6m
      PFR was 84%. Median PFS and OS were 11.8 and 24.1months, respectively. Overall RR
      and disease control rate were 72% and 88%, respectively. CONCLUSION: Lacking
      randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab
      might be a reasonable option for the first-line treatment of BRAF mutant mCRC
      patients.

PMID- 24138832
TI  - Coupled hydrodynamic and wastewater plume models of Belfast Lough, Northern
      Ireland: a predictive tool for future ecological studies.
AB  - Wastewater outfalls provide a natural laboratory for the study of nutrient
      dynamics in coastal seas, however if properly designed and operated their impact
      can be difficult to detect. A model was developed and applied to investigate the
      effect of variation in hydrodynamic conditions on the transport and dilution of a
      treated wastewater plume in Belfast Lough, Northern Ireland. To validate these
      predictions we measured the physiochemical properties of the waters surrounding
      the outfall with a specific focus on inherent plume tracers likely to be relevant
      to the study of macroalgae (salinity, nitrogen and phosphorus). The model
      performed well and our data show high dilution of the plume, even under neap-tide
      conditions. This provides a spatially and temporally defined predictive framework
      for future studies investigating the compliance of Northern Ireland's coastal
      waters with European Water Framework Directive objectives and for feasibility
      studies investigating macroalgal aquaculture near wastewater outfalls. 

PMID- 24138833
TI  - Vertical profile, sources, and equivalent toxicity of polycyclic aromatic
      hydrocarbons in sediment cores from the river mouths of Kaohsiung Harbor, Taiwan.
AB  - Six sediment cores collected at four contaminated river mouths and two harbor
      entrances in Kaohsiung Harbor (Taiwan) were analyzed to evaluate the sources and
      potential toxicity of polycyclic aromatic hydrocarbons (PAHs). PAHs presented the
      wide variations ranging from 369+/-656 to 33,772+/-14,378 ng g(-1) at the six
      sampling sites. The composition of PAHs presented a uniform profile reflecting
      the importance of atmospheric input from vehicle exhausts or coal combustion in
      the river mouths. PAHs diagnostic ratios indicated a stronger influence of coal
      combustion in the Salt River mouth and the prevalence of petroleum combustion and
      mixed sources in the other rivers and harbor entrances. PAHs toxicity assessment
      using the mean effect range-median quotient (m-ERM-q: 0.011-1.804),
      benzo[a]pyrene-toxicity equivalent (TEQ(carc): 22-2819 ng TEQ g(-1)), and dioxin
      toxicity equivalent (TEQ(fish): 37-5129 pg TEQ g(-1)) identified the Salt River
      mouth near the industrial area of the harbor as the most affected area.

PMID- 24138834
TI  - Utilizing participation in meaningful occupation as an intervention approach to
      support the acute model of inpatient palliative care.
AB  - Palliative care is a model of care that aims to improve quality of life (QOL) for
      patients and their families/carers who are facing the challenges associated with
      a life limiting illness (WHO, 2012). Until recently, palliative care has been
      seen to be largely focused on the medical management of specific symptoms, with
      little or no consideration given to the patient's occupational identity and
      goals. Occupational therapy is a profession whose core philosophy is grounded in
      occupational participation. Occupational therapists have the skills and expertise
      to incorporate an individual's occupational performance goals into their
      treatment plan, thereby helping people to participate in personally meaningful
      occupations, within the limitations of their illness and physical capacity. The
      present article aims to illustrate (using case-study examples) how personally
      meaningful occupational participation can better support an acute model of
      palliative care practice, resulting in better patient outcomes and improved
      quality of life for both patients and their carers. 

PMID- 24138835
TI  - WMS practice guidelines development: commentary from the co-chairs of the WMS
      Practice Guidelines Committee.

PMID- 24138836
TI  - Injury patterns in recreational alpine skiing and snowboarding at a mountainside
      clinic.
AB  - OBJECTIVE: The purpose of this study was to examine the demographic and injury
      characteristics of skiing and snowboarding at a mountainside clinic. METHODS:
      Prospectively collected data of all acutely injured patients at the Big Sky
      Medical Clinic at the base of Big Sky Ski Area in the Northern Rocky Mountains
      were reviewed. A total of 1593 patients filled out the study questionnaire during
      the 1995-2000 and 2009-2010 ski seasons. Injury patterns by sport, demographics,
      and skill level were analyzed and compared over time. RESULTS: The mean overall
      age was 32.9 +/- 14.9 years, 35.4 +/- 15.2 for skiers and 23.6 +/- 9.5 for
      snowboarders (P < .01). The knee accounted for 43% of all skiing injuries, the
      shoulder 12%, and the thumb 8%. The wrist accounted for 18% of all snowboarding
      injuries, the shoulders 14%, and the ankle and knee each 13%. Beginner
      snowboarders were more likely to present with wrist injuries compared with
      intermediate (P = .04) and advanced snowboarders (P < .01). Demographic and
      injury patterns did not significantly change over time. CONCLUSIONS: At this
      mountainside clinic, the most frequent ski injuries are to the knee and shoulder,
      regardless of skill level. Beginning snowboarders most frequently injure their
      wrists whereas shoulder injuries remain frequent at all skill levels. Knowledge
      of these injury patterns may help manage patients who present for medical care in
      the prehospital setting as well as help in designing targeted educational tools
      for injury prevention.

PMID- 24138837
TI  - [Reconstruction of nasal skin defect].
AB  - There are many possibilities for nasal skin defect reconstruction. The purpose of
      this article is to highlight the important points to respect in order to achieve
      aesthetic results. The principles that must be observed in nasal reconstruction
      are recalled. The most interesting techniques are detailed and illustrated with
      clinical cases. 

PMID- 24138838
TI  - InterVA-4 as a public health tool for measuring HIV/AIDS mortality: a validation
      study from five African countries.
AB  - BACKGROUND: Reliable population-based data on HIV infection and AIDS mortality in
      sub-Saharan Africa are scanty, even though that is the region where most of the
      world's AIDS deaths occur. There is therefore a great need for reliable and valid
      public health tools for assessing AIDS mortality. OBJECTIVE: The aim of this
      article is to validate the InterVA-4 verbal autopsy (VA) interpretative model
      within African populations where HIV sero-status is recorded on a prospective
      basis, and examine the distribution of cause-specific mortality among HIV
      positive and HIV-negative people. DESIGN: Data from six sites of the Alpha
      Network, including HIV sero-status and VA interviews, were pooled. VA data
      according to the 2012 WHO format were extracted, and processed using the InterVA
      4 model into likely causes of death. The model was blinded to the sero-status
      data. Cases with known pre-mortem HIV infection status were used to determine the
      specificity with which InterVA-4 could attribute HIV/AIDS as a cause of death.
      Cause-specific mortality fractions by HIV infection status were calculated, and a
      person-time model was built to analyse adjusted cause-specific mortality rate
      ratios. RESULTS: The InterVA-4 model identified HIV/AIDS-related deaths with a
      specificity of 90.1% (95% CI 88.7-91.4%). Overall sensitivity could not be
      calculated, because HIV-positive people die from a range of causes. In a person
      time model including 1,739 deaths in 1,161,688 HIV-negative person-years observed
      and 2,890 deaths in 75,110 HIV-positive person-years observed, the mortality
      ratio HIV-positive:negative was 29.0 (95% CI 27.1-31.0), after adjustment for
      age, sex, and study site. Cause-specific HIV-positive:negative mortality ratios
      for acute respiratory infections, HIV/AIDS-related deaths, meningitis,
      tuberculosis, and malnutrition were higher than the all-cause ratio; all causes
      had HIV-positive:negative mortality ratios significantly higher than unity.
      CONCLUSIONS: These results were generally consistent with relatively small post
      mortem and hospital-based diagnosis studies in the literature. The high
      specificity in cause of death attribution achieved in relation to HIV status, and
      large differences between specific causes by HIV status, show that InterVA-4 is
      an effective and valid tool for assessing HIV-related mortality.

PMID- 24138839
TI  - Beyond the clinic: improving child health through evidence-based community
      development.
AB  - BACKGROUND: Promoting child wellbeing necessarily goes beyond the clinic as risks
      to child health and development are embedded in the social and physical
      environmental conditions in which children live. Pediatricians play a vital role
      in promoting the health of children in the communities they serve and can
      maximize their impact by advocating for and supporting efficacious, evidence
      based strategies in their communities. METHODS: To provide a succinct guide for
      community pediatric efforts to advance the wellbeing of all children and
      particularly disadvantaged children in a community, we conducted a theory-driven
      and structured narrative review to synthesize published systematic and meta
      analytic reviews of policy-relevant, local-level strategies addressing potent and
      malleable influences on child health and development. An exhaustive list of
      policy-relevant, local-level strategies for improving child health was used to
      conduct a comprehensive search of recent (1990-2012), English language peer
      reviewed published meta-analyses and systematic reviews in the 10 core databases
      of scientific literature. Our review of the literature encompassed six key
      conceptual domains of intervention foci, including distal influences of child
      health (i.e., income and resources, social cohesion, and physical environment)
      and proximal influences (i.e., family, school and peer). We examined intervention
      effects on four key domains of child health and development: cognitive
      development, social and emotional competence, psychological and behavioral
      wellbeing, and physical health. RESULTS: Published reviews were identified for 98
      distinct policy-relevant community interventions, evaluated across 288 outcomes.
      We classified 46 strategies as meeting scientific criteria for efficacy by having
      consistent, positive outcomes from high-quality trials (e.g., tenant-based rental
      assistance, neighborhood watch programs, urban design and land use policies,
      access to quality childcare services, class size reductions, after-school
      programs that promote personal/social skills). Another 21 strategies were
      classified as having consistent evidence of positive outcomes from high-quality
      observational studies only, while 28 strategies had insufficient evidence
      available to assess their effectiveness based on published reviews. We did not
      limit the review to studies conducted in the United States, but the vast majority
      of them were U.S.-based, and the results therefore are most applicable to the
      U.S. context. CONCLUSIONS: Based on our synthesis of published literature on
      community development strategies, we provide an illustration combining a
      comprehensive set of evidence-based strategies to promote child health and
      development across a wide-range of child health outcomes.

PMID- 24138840
TI  - Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden:
      endemic and imported diseases.
AB  - BACKGROUND: Amyloidoses are a heterogeneous group of progressive diseases caused
      by tissue deposition of misfolded proteins. According to the International
      Classification of Diseases, hereditary amyloidosis is divided into neuropathic
      and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has
      been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease
      that is treated by liver transplantation. The non-neuropathic form includes
      familial autoinflammatory diseases. As no incidence data on these hereditary
      diseases are available and as even diagnostic data on non-neuropathic forms are
      lacking we determined the incidence of these diseases and characterized non
      neuropathic conditions. METHODS: Patients were identified using data from the
      Swedish Hospital Discharge Register and from the Outpatient Register for 2001
      through 2008. All patients discharged with hereditary amyloidosis diagnoses were
      included and standardized incidence rates were calculated. RESULTS: Non
      neuropathic disease was diagnosed in 210 patients, with an incidence of 2.83 per
      million. FAP was diagnosed in 221 patients, with an incidence of 2.02 per
      million. Two northern provinces that are home to 5% of the Swedish population
      accounted for 77% of FAP cases; the incidence in one of them, West Bothnia, was
      100 times that in the rest of Sweden. Approximately 98% of non-neuropathic
      disease patients were immigrants, most of whom were from the Eastern
      Mediterranean area. Young Syrian descendants had the highest incidence rate,
      which was over 500-fold higher than that in individuals with Swedish parents.
      Even the early onset of these conditions identified them as familial
      autoinflammatory diseases. CONCLUSIONS: FAP cases were highly concentrated in the
      two northernmost provinces. Non-neuropathic familial autoinflammatory diseases
      were of early-onset and immigrant origin most likely related to periodic fever
      syndromes. Paradoxically, FAP has remained endemic, in spite of population
      movements within the country, while familial autoinflammatory diseases, with an
      incidence exceeding that of FAP, were brought into the country as a result of
      immigration mainly from the Eastern Mediterranean area.

PMID- 24138841
TI  - Molecular and protein markers for clinical decision making in breast cancer:
      today and tomorrow.
AB  - In early breast cancer (eBC), established clinicopathological factors are not
      sufficient for clinical decision making particularly regarding adjuvant
      chemotherapy since substantial over- or undertreatment may occur. Thus, novel
      protein- and molecular markers have been put forward as decision aids. Since
      these potential prognosis and/or predictive tests differ substantially regarding
      their methodology, analytical and clinical validation, this review attempts to
      summarize the essential facts for clinicians. This review focuses on those
      markers which are the most advanced so far in their development towards routine
      clinical application, i.e. two protein markers (i.e. uPA/PAI-1 and IHC4) and six
      molecular multigene tests (i.e. Mammaprint(r), Oncotype DX(r), PAM50,
      Endopredict(r), the 97-gene genomic grade, and 76 gene Rotterdam signatures).
      Next to methodological aspects, we summarized the clinical evidences, in
      particular the main prospective clinical trials which have already been fully
      recruited (i.e. MINDACT, TAILORx, WSG PLAN B) or are still ongoing (i.e.
      RxPONDER/SWOG S1007, WSG-ADAPT). Last but not least, this review points out the
      key elements for clinicians to select one test among the wide panel of proposed
      assays, for a specific population of patients in term of level of evidence,
      analytical and clinical validity as well as cost effectiveness. 

PMID- 24138842
TI  - CER1 gene variations associated with bone mineral density, bone markers, and
      early menopause in postmenopausal women.
AB  - BACKGROUND: Osteoporosis has a multifactorial pathogenesis characterized by a
      combination of low bone mass and increased fragility. In our study, we focused on
      the effects of polymorphisms in CER1 and DKK1 genes, recently reported as
      important susceptibility genes for osteoporosis, on bone mineral density (BMD)
      and bone markers in osteoporotic women. Our objective was to evaluate the effect
      of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene
      sequence and five selected CER1 SNPs were amplified and resequenced to assess
      whether there is a correlation between these genes and BMD, early menopause, and
      bone turnover markers in osteoporotic patients. RESULTS: Osteoporotic women seem
      to suffer menopause 2 years earlier than the control group. The entire DKK1 gene
      sequence analysis revealed six variations. There was no correlation between the
      six DKK1 variations and osteoporosis, in contrast to the five common CER1
      variations that were significantly associated with BMD. Additionally,
      osteoporotic patients with rs3747532 and rs7022304 CER1 variations had
      significantly higher serum levels of parathyroid hormone and calcitonin and lower
      serum levels of osteocalcin and IGF-1. CONCLUSIONS: No significant association
      between the studied DKK1 variations and osteoporosis was found, while CER1
      variations seem to play a significant role in the determination of osteoporosis
      and a potential predictive role, combined with bone markers, in postmenopausal
      osteoporotic women.

PMID- 24138844
TI  - Spiritual and religious beliefs: do they matter in the medication adherence
      behaviour of hypertensive patients?
AB  - BACKGROUND: Medication non-adherence is often a predominant problem in the
      management of hypertension and other chronic conditions. In explaining health
      behaviours, social determinants like spirituality and religiosity are
      increasingly identified to impact health and treatment. Although a number of
      researchers have found spirituality and religiosity to be primary resources among
      persons dealing with chronic disability and illness, studies relating this
      specifically to medication adherence have been limited. METHODS: Our study sought
      to examine the interrelationship between spirituality/ religiosity and medication
      adherence among 400 hypertensive patients 18 years old and above. Spiritual
      Perspective Scale, Duke Religion Index, and the Morisky Medication Adherence
      Scale were used to determine spirituality, religiosity and medication adherence
      respectively. RESULTS: The majority (93.25%) of patients poorly adhered to their
      medications. While high spiritual and religious beliefs formed core components of
      the lifestyles of patients, spirituality (p = 0.018) and not religiosity (p =
      0.474) related directly with medication non-adherence. Likewise, after
      controlling for demography and other medical co-morbidities, patients with high
      spirituality were 2.68 times more likely to be poorly adherent than patients who
      place lower emphasis on the association between spirituality and health.
      CONCLUSION: Our study suggests that while spirituality/ religiosity was dominant
      among hypertensive patients, these spiritual attachments of patients with a
      supreme being potentially increased their trust in the expectation of divine
      healing instead of adhering adequately with their anti-hypertensive medications.

PMID- 24138845
TI  - Antidepressant-like effects of the aqueous macerate of the bulb of Gladiolus
      dalenii Van Geel (Iridaceae) in a rat model of epilepsy-associated depression.
AB  - BACKGROUND: In Cameroonian traditional medicine various extracts of Gladiolus
      dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that
      include headaches, digestive problems, muscle and joint aches, and some central
      nervous system disorders such as epilepsy, schizophrenia and mood disorders.
      Owning to this background, the aim of the study was to investigate whether an
      aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity
      focusing specifically on depression-like behaviours associated with epilepsy.
      METHOD: We used the combined administration of atropine and pilocarpine to rats
      as our animal model of epilepsy. The forced swim test and spontaneous locomotor
      activity in the open field test were the two tools used to assess the presence of
      depression-like behaviour in epileptic and control animals. The following
      depression-related parameters were determined: plasma ACTH, plasma
      corticosterone, adrenal gland weight and hippocampal levels of brain-derived
      neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to
      that of fluoxetine. RESULTS: Our results showed that we had a valid animal model
      of epilepsy-induced depression as all 3 measures of construct, predictive and
      face validity were satisfied. The data indicated that Gladiolus dalenii
      significantly reduced the immobility times in the forced swim test and the
      locomotor activity as assessed in the open field. A similar pattern was observed
      when the HPA axis parameters were analysed. Gladiolus dalenii significantly
      reduced the levels of ACTH, corticosterone, but not the adrenal gland weight.
      Gladiolus dalenii significantly increased the level of BDNF in the hippocampus.
      In all parameters measured the effects of Gladiolus dalenii were significantly
      greater than those of fluoxetine. CONCLUSION: The results show that Gladiolus
      dalenii has antidepressant-like properties similar to those of fluoxetine in
      epilepsy-associated depressive states. The antidepressant activity of Gladiolus
      dalenii is likely to be mediated by restoring the activity of the HPA axis and
      increasing the levels of BDNF in the hippocampus.

PMID- 24138846
TI  - Operator functional state classification using least-square support vector
      machine based recursive feature elimination technique.
AB  - This paper proposed two psychophysiological-data-driven classification frameworks
      for operator functional states (OFS) assessment in safety-critical human-machine
      systems with stable generalization ability. The recursive feature elimination
      (RFE) and least square support vector machine (LSSVM) are combined and used for
      binary and multiclass feature selection. Besides typical binary LSSVM classifiers
      for two-class OFS assessment, two multiclass classifiers based on multiclass
      LSSVM-RFE and decision directed acyclic graph (DDAG) scheme are developed, one
      used for recognizing the high mental workload and fatigued state while the other
      for differentiating overloaded and base-line states from the normal states.
      Feature selection results have revealed that different dimensions of OFS can be
      characterized by specific set of psychophysiological features. Performance
      comparison studies show that reasonable high and stable classification accuracy
      of both classification frameworks can be achieved if the RFE procedure is
      properly implemented and utilized. 

PMID- 24138843
TI  - Targeted therapy against EGFR and VEGFR using ZD6474 enhances the therapeutic
      potential of UV-B phototherapy in breast cancer cells.
AB  - BACKGROUND: The hypoxic environment of tumor region stimulated the up regulation
      of growth factors responsible for angiogenesis and tumor proliferation. Thus,
      targeting the tumor vasculature along with the proliferation by dual tyrosine
      kinase inhibitor may be the efficient way of treating advanced breast cancers,
      which can be further enhanced by combining with radiotherapy. However, the
      effectiveness of radiotherapy may be severely compromised by toxicities and tumor
      resistance due to radiation-induced adaptive response contributing to recurrence
      and metastases of breast cancer. The rational of using ZD6474 is to evaluate the
      feasibility and efficacy of combined VEGFR2 and EGFR targeting with concurrent
      targeted and localized UV-B phototherapy in vitro breast cancer cells with the
      anticipation to cure skin lesions infiltrated with breast cancer cells. MATERIALS
      AND METHODS: Breast cancer cells were exposed to UV-B and ZD6474 and the cell
      viability, apoptosis, invasion and motility studies were conducted for the
      combinatorial effect. Graphs and statistical analyses were performed using Graph
      Pad Prism 5.0. RESULTS: ZD6474 and UV-B decreased cell viability in breast
      cancers in combinatorial manner without affecting the normal human mammary
      epithelial cells. ZD6474 inhibited cyclin E expression and induced p53 expression
      when combined with UV-B. It activated stress induced mitochondrial pathway by
      inducing translocation of bax and cytochrome-c. The combination of ZD6474 with UV
      B vs. either agent alone also more potently down-regulated the anti-apoptotic bcl
      2 protein, up-regulated pro-apoptotic signaling events involving expression of
      bax, activation of caspase-3 and caspase-7 proteins, and induced poly (ADP
      ribose) polymerase resulting in apoptosis. ZD6474 combined with UV-B inhibited
      invasion of breast cancer cells in vitro as compared to either single agent,
      indicating a potential involvement of pro-angiogenic growth factors in regulating
      the altered expression and reorganization of cytoskeletal proteins in
      combinatorial treated breast cancer cells. Involvement of combination therapy in
      reducing the expression of matrix metalloprotease was also observed. CONCLUSIONS:
      Collectively, our studies indicate that incorporating an anti-EGFR plus VEGFR
      strategy (ZD6474) with phototherapy (UV-B), an alternative approach to the
      ongoing conventional radiotherapy for the treatment of infiltrating metastatic
      breast cancer cells in the skin and for locally recurrence breast cancer than
      either approach alone.

PMID- 24138847
TI  - Mechanical players-The role of intermediate filaments in cell mechanics and
      organization.

PMID- 24138848
TI  - Being Squeezed into the Right Place within the Egg Shell.

PMID- 24138849
TI  - K(+) and Na(+) conduction in selective and nonselective ion channels via
      molecular dynamics simulations.
AB  - Generations of scientists have been captivated by ion channels and how they
      control the workings of the cell by admitting ions from one side of the cell
      membrane to the other. Elucidating the molecular determinants of ion conduction
      and selectivity are two of the most fundamental issues in the field of
      biophysics. Combined with ongoing progress in structural studies, modeling and
      simulation have been an integral part of the development of the field. As of this
      writing, the relentless growth in computational power, the development of new
      algorithms to tackle the so-called rare events, improved force-field parameters,
      and the concomitant increasing availability of membrane protein structures, allow
      simulations to contribute even further, providing more-complete models of ion
      conduction and selectivity in ion channels. In this report, we give an overview
      of the recent progress made by simulation studies on the understanding of ion
      permeation in selective and nonselective ion channels.

PMID- 24138850
TI  - Measuring actin flow in 3D cell protrusions.
AB  - Actin dynamics is important in determining cell shape, tension, and migration.
      Methods such as fluorescent speckle microscopy and spatial temporal image
      correlation spectroscopy have been used to capture high-resolution actin turnover
      dynamics within cells in two dimensions. However, these methods are not directly
      applicable in 3D due to lower resolution and poor contrast. Here, we propose to
      capture actin flow in 3D with high spatial-temporal resolution by combining
      nanoscale precise imaging by rapid beam oscillation and fluctuation spectroscopy
      techniques. To measure the actin flow along cell protrusions in cell expressing
      actin-eGFP cultured in a type I collagen matrix, the laser was orbited around the
      protrusion and its trajectory was modulated in a clover-shaped pattern
      perpendicularly to the protrusion. Orbits were also alternated at two positions
      closely spaced along the protrusion axis. The pair cross-correlation function was
      applied to the fluorescence fluctuation from these two positions to capture the
      flow of actin. Measurements done on nonmoving cellular protrusion tips showed no
      pair-correlation at two orbital positions indicating a lack of flow of F-actin
      bundles. However, in some protrusions, the pair-correlation approach revealed
      directional flow of F-actin bundles near the protrusion surface with flow rates
      in the range of ~1 MUm/min, comparable to results in two dimensions using
      fluorescent speckle microscopy. Furthermore, we found that the actin flow rate is
      related to the distance to the protrusion tip. We also observed collagen
      deformation by concomitantly detecting collagen fibers with reflectance detection
      during these actin motions. The implementation of the nanoscale precise imaging
      by rapid beam oscillation method with a cloverleaf-shaped trajectory in
      conjunction with the pair cross-correlation function method provides a
      quantitative way of capturing dynamic flows and organization of proteins during
      cell migration in 3D in conditions of poor contrast.

PMID- 24138851
TI  - Electronic transitions and heterogeneity of the bacteriophytochrome Pr absorption
      band: An angle balanced polarization resolved femtosecond VIS pump-IR probe
      study.
AB  - Photoisomerization of biliverdin (BV) chromophore triggers the photoresponse in
      native Agp1 bacteriophytochrome. We discuss heterogeneity in phytochrome Pr form
      to account for the shape of the absorption profile. We investigated different
      regions of the absorption profile by angle balanced polarization resolved
      femtosecond VIS pump-IR probe spectroscopy. We studied the Pr form of Agp1 with
      its natural chromophore and with a sterically locked 18Et-BV (locked Agp1). We
      followed the dynamics and orientations of the carbonyl stretching vibrations of
      ring D and ring A in their ground and electronically excited states.
      Photoisomerization of ring D is reflected by strong signals of the ring D
      carbonyl vibration. In contrast, orientational data on ring A show no rotation of
      ring A upon photoexcitation. Orientational data allow excluding a ZZZasa geometry
      and corroborates a nontwisted ZZZssa geometry of the chromophore. We found no
      proof for heterogeneity but identified a new, to our knowledge, electronic
      transition in the absorption profile at 644 nm (S0->S2). Excitation of the S0->S2
      transition will introduce a more complex photodynamics compared with S0->S1
      transition. Our approach provides fundamental information on disentanglement of
      absorption profiles, identification of chromophore structures, and determination
      of molecular groups involved in the photoisomerization process of photoreceptors.

PMID- 24138852
TI  - Mechanical fluidity of fully suspended biological cells.
AB  - Mechanical characteristics of single biological cells are used to identify and
      possibly leverage interesting differences among cells or cell populations.
      Fluidity-hysteresivity normalized to the extremes of an elastic solid or a
      viscous liquid-can be extracted from, and compared among, multiple rheological
      measurements of cells: creep compliance versus time, complex modulus versus
      frequency, and phase lag versus frequency. With multiple strategies available for
      acquisition of this nondimensional property, fluidity may serve as a useful and
      robust parameter for distinguishing cell populations, and for understanding the
      physical origins of deformability in soft matter. Here, for three disparate
      eukaryotic cell types deformed in the suspended state via optical stretching, we
      examine the dependence of fluidity on chemical and environmental influences at a
      timescale of ~1 s. We find that fluidity estimates are consistent in the time and
      frequency domains under a structural damping (power-law or fractional-derivative)
      model, but not under an equivalent-complexity, lumped-component (spring-dashpot)
      model; the latter predicts spurious time constants. Although fluidity is
      suppressed by chemical cross-linking, we find that ATP depletion in the cell does
      not measurably alter the parameter, and we thus conclude that active ATP-driven
      events are not a crucial enabler of fluidity during linear viscoelastic
      deformation of a suspended cell. Finally, by using the capacity of optical
      stretching to produce near-instantaneous increases in cell temperature, we
      establish that fluidity increases with temperature-now measured in a fully
      suspended, sortable cell without the complicating factor of cell-substratum
      adhesion.

PMID- 24138853
TI  - The small heat shock protein Hsp27 affects assembly dynamics and structure of
      keratin intermediate filament networks.
AB  - The mechanical properties of living cells are essential for many processes. They
      are defined by the cytoskeleton, a composite network of protein fibers. Thus, the
      precise control of its architecture is of paramount importance. Our knowledge
      about the molecular and physical mechanisms defining the network structure
      remains scarce, especially for the intermediate filament cytoskeleton. Here, we
      investigate the effect of small heat shock proteins on the keratin 8/18
      intermediate filament cytoskeleton using a well-controlled model system of
      reconstituted keratin networks. We demonstrate that Hsp27 severely alters the
      structure of such networks by changing their assembly dynamics. Furthermore, the
      C-terminal tail domain of keratin 8 is shown to be essential for this effect.
      Combining results from fluorescence and electron microscopy with data from
      analytical ultracentrifugation reveals the crucial role of kinetic trapping in
      keratin network formation.

PMID- 24138854
TI  - Physical origin of the contact frequency in chromosome conformation capture data.
AB  - Physical proximity between each pair of genomic loci in a nucleus is measured as
      a form of contact frequency in chromosome conformation capture-based methods.
      Complexity of chromosome structure in interphase can be characterized by
      measuring a statistical property of physical distance between genomic loci
      according to genomic separation along single chromatids. To find a relationship
      between the physical distance and the contact frequency, we propose a polymer
      model derived from the Langevin equation. The model is derived by considering a
      structure of a chromosome as a trajectory of a particle, where each consecutive
      segment in the chromosome corresponds to a transient position in the trajectory
      over time. Using chromosome conformation capture data, we demonstrate the
      functional relationship between the two quantities. The physical distances
      derived from the mean contact frequencies by the model show a good correlation
      with those from experimental data. From the model, we present that the mean
      contact frequency curve can be divided into three components that arise from
      different physical origins and show that the contact frequency is proportional to
      the contact surface area, not to the volume of segments suggested by the fractal
      globule model. The model explains both a decaying pattern of the contact
      frequency and the biphasic relationship between the physical distance and the
      genomic length.

PMID- 24138855
TI  - A new angle on microscopic suspension feeders near boundaries.
AB  - Microscopic sessile suspension feeders are a critical component in aquatic
      ecosystems, acting as an intermediate trophic stage between bacteria and higher
      eukaryotic taxa. Because they live attached to boundaries, it has long been
      thought that recirculation of the feeding currents produced by sessile suspension
      feeders inhibits their ability to access fresh fluid. However, previous models
      for the feeding flows of these organisms assume that they feed by pushing fluid
      perpendicular to surfaces they live upon, whereas we observe that sessile
      suspension feeders often feed at an angle to these boundaries. Using experiments
      and calculations, we show that living suspension feeders (Vorticella) likely
      actively regulate the angle that they feed relative to a substratum. We then use
      theory and simulations to show that angled feeding increases nutrient and
      particle uptake by reducing the reprocessing of depleted water. This work
      resolves an open question of how a key class of suspension-feeding organisms
      escapes physical limitations associated with their sessile lifestyle.

PMID- 24138856
TI  - Mechanical cues in the early embryogenesis of Caenorhabditis elegans.
AB  - Biochemical signaling pathways in developmental processes have been extensively
      studied, yet the role of mechanical cues during embryogenesis is much less
      explored. Here we have used selective plane illumination microscopy in
      combination with a simple mechanical model to quantify and rationalize cell
      motion during early embryogenesis of the small nematode Caenorhabditis elegans.
      As a result, we find that cell organization in the embryo until gastrulation is
      well described by a purely mechanical model that predicts cells to assume
      positions in which they face the least repulsive interactions from other cells
      and the embryo's egg shell. Our findings therefore suggest that mechanical
      interactions are key for a rapid and robust cellular arrangement during early
      embryogenesis of C. elegans.

PMID- 24138857
TI  - Phosphorylated phospholamban stabilizes a compact conformation of the cardiac
      calcium-ATPase.
AB  - The sarcoendoplasmic reticulum calcium ATPase (SERCA) plays a key role in cardiac
      calcium handling and is considered a high-value target for the treatment of heart
      failure. SERCA undergoes conformational changes as it harnesses the chemical
      energy of ATP for active transport. X-ray crystallography has provided insight
      into SERCA structural substates, but it is not known how well these static
      snapshots describe in vivo conformational dynamics. The goals of this work were
      to quantify the direction and magnitude of SERCA motions as the pump performs
      work in live cardiac myocytes, and to identify structural determinants of SERCA
      regulation by phospholamban. We measured intramolecular fluorescence resonance
      energy transfer (FRET) between fluorescent proteins fused to SERCA cytoplasmic
      domains. We detected four discrete structural substates for SERCA expressed in
      cardiac muscle cells. The relative populations of these discrete states
      oscillated with electrical pacing. Low FRET states were most populated in low Ca
      (diastole), and were indicative of an open, disordered structure for SERCA in the
      E2 (Ca-free) enzymatic substate. High FRET states increased with Ca (systole),
      suggesting rigidly closed conformations for the E1 (Ca-bound) enzymatic
      substates. Notably, a special compact E1 state was observed after treatment with
      beta-adrenergic agonist or with coexpression of phosphomimetic mutants of
      phospholamban. The data suggest that SERCA calcium binding induces the pump to
      undergo a transition from an open, dynamic conformation to a closed, ordered
      structure. Phosphorylated phospholamban stabilizes a unique conformation of SERCA
      that is characterized by a compact architecture.

PMID- 24138858
TI  - IR laser-induced perturbations of the voltage-dependent solute carrier protein
      SLC26a5.
AB  - Alterations in membrane capacitance can arise from linear and nonlinear sources.
      For example, changes in membrane surface area or dielectric properties can modify
      capacitance linearly, whereas sensor residues of voltage-dependent proteins can
      modify capacitance nonlinearly. Here, we examined the effects of fast temperature
      jumps induced by an infrared (IR) laser in control and prestin (SLC26a5)
      transfected human embryonic kidney (HEK) cells under whole-cell voltage clamp.
      Prestin's voltage sensor imparts a characteristic bell-shaped, voltage-dependent
      nonlinear capacitance (NLC). Temperature jumps in control HEK cells cause a
      monophasic increase in membrane capacitance (Cm) regardless of holding voltage
      due to double-layer effects. Prestin-transfected HEK cells, however, additionally
      show a biphasic increase/decrease in Cm with a reversal potential corresponding
      to the voltage at peak NLC of prestin (Vh), attributable to a rapid temperature
      following shift in Vh, with shift rates up to 14 V/s over the course of a 5 ms IR
      pulse. Treatment with salicylate, a known inhibitor of NLC, reestablishes control
      cell behavior. A simple kinetic model recapitulates our biophysical observations.
      These results verify a voltage-dependent protein's ability to respond to fast
      temperature perturbations on a par with double-layer susceptibility. This likely
      arises from prestin's unique ability to move sensor charge at kilohertz rates,
      which is required for the outer hair cells' role as a cochlear amplifier.

PMID- 24138859
TI  - Molecular dynamics simulations of scorpion toxin recognition by the Ca(2+)
      activated potassium channel KCa3.1.
AB  - The Ca(2+)-activated channel of intermediate-conductance (KCa3.1) is a target for
      antisickling and immunosuppressant agents. Many small peptides isolated from
      animal venoms inhibit KCa3.1 with nanomolar affinities and are promising drug
      scaffolds. Although the inhibitory effect of peptide toxins on KCa3.1 has been
      examined extensively, the structural basis of toxin-channel recognition has not
      been understood in detail. Here, the binding modes of two selected scorpion
      toxins, charybdotoxin (ChTx) and OSK1, to human KCa3.1 are examined in atomic
      detail using molecular dynamics (MD) simulations. Employing a homology model of
      KCa3.1, we first determine conduction properties of the channel using Brownian
      dynamics and ascertain that the simulated results are in accord with experiment.
      The model structures of ChTx-KCa3.1 and OSK1-KCa3.1 complexes are then
      constructed using MD simulations biased with distance restraints. The ChTx-KCa3.1
      complex predicted from biased MD is consistent with the crystal structure of ChTx
      bound to a voltage-gated K(+) channel. The dissociation constants (Kd) for the
      binding of both ChTx and OSK1 to KCa3.1 determined experimentally are reproduced
      within fivefold using potential of mean force calculations. Making use of the
      knowledge we gained by studying the ChTx-KCa3.1 complex, we attempt to enhance
      the binding affinity of the toxin by carrying out a theoretical mutagenesis. A
      mutant toxin, in which the positions of two amino acid residues are interchanged,
      exhibits a 35-fold lower Kd value for KCa3.1 than that of the wild-type. This
      study provides insight into the key molecular determinants for the high-affinity
      binding of peptide toxins to KCa3.1, and demonstrates the power of computational
      methods in the design of novel toxins.

PMID- 24138860
TI  - The structural basis of cholesterol accessibility in membranes.
AB  - Although the majority of free cellular cholesterol is present in the plasma
      membrane, cholesterol homeostasis is principally regulated through sterol-sensing
      proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In
      response to acute cholesterol loading or depletion, there is rapid equilibration
      between the ER and plasma membrane cholesterol pools, suggesting a biophysical
      model in which the availability of plasma membrane cholesterol for trafficking to
      internal membranes modulates ER membrane behavior. Previous studies have
      predominantly examined cholesterol availability in terms of binding to
      extramembrane acceptors, but have provided limited insight into the structural
      changes underlying cholesterol activation. In this study, we use both molecular
      dynamics simulations and experimental membrane systems to examine the behavior of
      cholesterol in membrane bilayers. We find that cholesterol depth within the
      bilayer provides a reasonable structural metric for cholesterol availability and
      that this is correlated with cholesterol-acceptor binding. Further, the
      distribution of cholesterol availability in our simulations is continuous rather
      than divided into distinct available and unavailable pools. This data provide
      support for a revised cholesterol activation model in which activation is driven
      not by saturation of membrane-cholesterol interactions but rather by bulk
      membrane remodeling that reduces membrane-cholesterol affinity.

PMID- 24138861
TI  - Effects of detergent beta-octylglucoside and phosphate salt solutions on phase
      behavior of monoolein mesophases.
AB  - Using small-angle x-ray scattering (SAXS), we investigated the phase behavior of
      mesophases of monoolein (MO) mixed with additives commonly used for the
      crystallization of membrane proteins from lipidic mesophases. In particular, we
      examined the effect of sodium and potassium phosphate salts and the detergent
      beta-octylglucoside (betaOG) over a wide range of compositions relevant for the
      crystallization of membrane proteins in lipidic mesophases. We studied two types
      of systems: 1), ternary mixtures of MO with salt solutions above the hydration
      boundary; and 2), quaternary mixtures of MO with betaOG and salt solutions over a
      wide range of hydration conditions. All quaternary mixtures showed highly regular
      lyotropic phase behavior with the same sequence of phases (Lalpha, Ia3d, and
      Pn3m) as MO/water mixtures at similar temperatures. The effects of additives in
      quaternary systems agreed qualitatively with those found in ternary mixtures in
      which only one additive is present. However, quantitative differences in the
      effects of additives on the lattice parameters of fully hydrated mesophases were
      found between ternary and quaternary mixtures. We discuss the implications of
      these findings for mechanistic investigations of membrane protein crystallization
      in lipidic mesophases and for studies of the suitability of precipitants for
      mesophase-based crystallization methods.

PMID- 24138862
TI  - Cohesiveness tunes assembly and morphology of FG nucleoporin domain meshworks -
      Implications for nuclear pore permeability.
AB  - Nuclear pore complexes control the exchange of macromolecules between the
      cytoplasm and the nucleus. A selective permeability barrier that arises from a
      supramolecular assembly of intrinsically unfolded nucleoporin domains rich in
      phenylalanine-glycine dipeptides (FG domains) fills the nuclear pore. There is
      increasing evidence that selective transport requires cohesive FG domain
      interactions. To understand the functional roles of cohesive interactions, we
      studied monolayers of end-grafted FG domains as a bottom-up nanoscale model
      system of the permeability barrier. Based on detailed physicochemical analysis of
      the model films and comparison of the data with polymer theory, we propose that
      cohesiveness is tuned to promote rapid assembly of the permeability barrier and
      to generate a stable and compact pore-filling meshwork with a small mesh size.
      Our results highlight the functional importance of weak interactions, typically a
      few kBT per chain, and contribute important information to understand the
      mechanism of size-selective transport.

PMID- 24138863
TI  - Nonlinear cross-bridge elasticity and post-power-stroke events in fast skeletal
      muscle actomyosin.
AB  - Generation of force and movement by actomyosin cross-bridges is the molecular
      basis of muscle contraction, but generally accepted ideas about cross-bridge
      properties have recently been questioned. Of the utmost significance, evidence
      for nonlinear cross-bridge elasticity has been presented. We here investigate how
      this and other newly discovered or postulated phenomena would modify cross-bridge
      operation, with focus on post-power-stroke events. First, as an experimental
      basis, we present evidence for a hyperbolic [MgATP]-velocity relationship of
      heavy-meromyosin-propelled actin filaments in the in vitro motility assay using
      fast rabbit skeletal muscle myosin (28-29 degrees C). As the hyperbolic [MgATP]
      velocity relationship was not consistent with interhead cooperativity, we
      developed a cross-bridge model with independent myosin heads and strain-dependent
      interstate transition rates. The model, implemented with inclusion of MgATP
      independent detachment from the rigor state, as suggested by previous single
      molecule mechanics experiments, accounts well for the [MgATP]-velocity
      relationship if nonlinear cross-bridge elasticity is assumed, but not if linear
      cross-bridge elasticity is assumed. In addition, a better fit is obtained with
      load-independent than with load-dependent MgATP-induced detachment rate. We
      discuss our results in relation to previous data showing a nonhyperbolic [MgATP]
      velocity relationship when actin filaments are propelled by myosin subfragment 1
      or full-length myosin. We also consider the implications of our results for
      characterization of the cross-bridge elasticity in the filament lattice of
      muscle.

PMID- 24138864
TI  - Probing the flexibility of tropomyosin and its binding to filamentous actin using
      molecular dynamics simulations.
AB  - Tropomyosin (Tm) is a coiled-coil protein that binds to filamentous actin (F
      actin) and regulates its interactions with actin-binding proteins like myosin by
      moving between three positions on F-actin (the blocked, closed, and open
      positions). To elucidate the molecular details of Tm flexibility in relation to
      its binding to F-actin, we conducted extensive molecular dynamics simulations for
      both Tm alone and Tm-F-actin complex in the presence of explicit solvent (total
      simulation time >400 ns). Based on the simulations, we systematically analyzed
      the local flexibility of the Tm coiled coil using multiple parameters. We found a
      good correlation between the regions with high local flexibility and a number of
      destabilizing regions in Tm, including six clusters of core alanines. Despite the
      stabilization by F-actin binding, the distribution of local flexibility in Tm is
      largely unchanged in the absence and presence of F-actin. Our simulations showed
      variable fluctuations of individual Tm periods from the closed position toward
      the open position. In addition, we performed Tm-F-actin binding calculations
      based on the simulation trajectories, which support the importance of Tm
      flexibility to Tm-F-actin binding. We identified key residues of Tm involved in
      its dynamic interactions with F-actin, many of which have been found in recent
      mutational studies to be functionally important, and the rest of which will make
      promising targets for future mutational experiments.

PMID- 24138865
TI  - Structural transitions and energy landscape for Cowpea Chlorotic Mottle Virus
      capsid mechanics from nanomanipulation in vitro and in silico.
AB  - Physical properties of capsids of plant and animal viruses are important factors
      in capsid self-assembly, survival of viruses in the extracellular environment,
      and their cell infectivity. Combined AFM experiments and computational modeling
      on subsecond timescales of the indentation nanomechanics of Cowpea Chlorotic
      Mottle Virus capsid show that the capsid's physical properties are dynamic and
      local characteristics of the structure, which change with the depth of
      indentation and depend on the magnitude and geometry of mechanical input. Under
      large deformations, the Cowpea Chlorotic Mottle Virus capsid transitions to the
      collapsed state without substantial local structural alterations. The enthalpy
      change in this deformation state DeltaHind = 11.5-12.8 MJ/mol is mostly due to
      large-amplitude out-of-plane excitations, which contribute to the capsid bending;
      the entropy change TDeltaSind = 5.1-5.8 MJ/mol is due to coherent in-plane
      rearrangements of protein chains, which mediate the capsid stiffening. Direct
      coupling of these modes defines the extent of (ir)reversibility of capsid
      indentation dynamics correlated with its (in)elastic mechanical response to the
      compressive force. This emerging picture illuminates how unique physico-chemical
      properties of protein nanoshells help define their structure and morphology, and
      determine their viruses' biological function.

PMID- 24138866
TI  - Temperature dependence of the DNA double helix at the nanoscale: structure,
      elasticity, and fluctuations.
AB  - Biological organisms exist over a broad temperature range of -15 degrees C to
      +120 degrees C, where many molecular processes involving DNA depend on the
      nanoscale properties of the double helix. Here, we present results of extensive
      molecular dynamics simulations of DNA oligomers at different temperatures. We
      show that internal basepair conformations are strongly temperature-dependent,
      particularly in the stretch and opening degrees of freedom whose harmonic
      fluctuations can be considered the initial steps of the DNA melting pathway. The
      basepair step elasticity contains a weaker, but detectable, entropic contribution
      in the roll, tilt, and rise degrees of freedom. To extend the validity of our
      results to the temperature interval beyond the standard melting transition
      relevant to extremophiles, we estimate the effects of superhelical stress on the
      stability of the basepair steps, as computed from the Benham model. We predict
      that although the average twist decreases with temperature in vitro, the
      stabilizing external torque in vivo results in an increase of ~1 degrees /bp (or
      a superhelical density of Deltasigma ? +0.03) in the interval 0-100 degrees C. In
      the final step, we show that the experimentally observed apparent bending
      persistence length of torsionally unconstrained DNA can be calculated from a
      hybrid model that accounts for the softening of the double helix and the presence
      of transient denaturation bubbles. Although the latter dominate the behavior
      close to the melting transition, the inclusion of helix softening is important
      around standard physiological temperatures.

PMID- 24138867
TI  - A bacterial swimmer with two alternating speeds of propagation.
AB  - We recorded large data sets of swimming trajectories of the soil bacterium
      Pseudomonas putida. Like other prokaryotic swimmers, P. putida exhibits a motion
      pattern dominated by persistent runs that are interrupted by turning events. An
      in-depth analysis of their swimming trajectories revealed that the majority of
      the turning events is characterized by an angle of phi1 = 180 degrees 
      (reversals). To a lesser extent, turning angles of phi2 = 0 degrees  are also
      found. Remarkably, we observed that, upon a reversal, the swimming speed changes
      by a factor of two on average-a prominent feature of the motion pattern that, to
      our knowledge, has not been reported before. A theoretical model, based on the
      experimental values for the average run time and the rotational diffusion,
      recovers the mean-square displacement of P. putida if the two distinct swimming
      speeds are taken into account. Compared to a swimmer that moves with a constant
      intermediate speed, the mean-square displacement is strongly enhanced. We
      furthermore observed a negative dip in the directional autocorrelation at
      intermediate times, a feature that is only recovered in an extended model, where
      the nonexponential shape of the run-time distribution is taken into account.

PMID- 24138868
TI  - Sensitivity and robustness in covalent modification cycles with a bifunctional
      converter enzyme.
AB  - Regulation by covalent modification is a common mechanism to transmit signals in
      biological systems. The modifying reactions are catalyzed either by two distinct
      converter enzymes or by a single bifunctional enzyme (which may employ either one
      or two catalytic sites for its opposing activities). The reason for this
      diversification is unclear, but contemporary theoretical models predict that
      systems with distinct converter enzymes can exhibit enhanced sensitivity to input
      signals whereas bifunctional enzymes with two catalytic sites are believed to
      generate robustness against variations in system's components. However,
      experiments indicate that bifunctional enzymes can also exhibit enhanced
      sensitivity due to the zero-order effect, raising the question whether both
      phenomena could be understood within a common mechanistic model. Here, I argue
      that this is, indeed, the case. Specifically, I show that bifunctional enzymes
      with two catalytic sites can exhibit both ultrasensitivity and concentration
      robustness, depending on the kinetic operating regime of the enzyme's opposing
      activities. The model predictions are discussed in the context of experimental
      observations of ultrasensitivity and concentration robustness in the
      uridylylation cycle of the PII protein, and in the phosphorylation cycle of the
      isocitrate dehydrogenase, respectively.

PMID- 24138869
TI  - Fluid balance and cardiac function in septic shock as predictors of hospital
      mortality.
AB  - INTRODUCTION: Septic shock is a major cause of morbidity and mortality throughout
      the world. Unfortunately, the optimal fluid management of septic shock is unknown
      and currently is empirical. METHODS: A retrospective analysis was performed at
      Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325)
      hospitalized with septic shock who had echocardiographic examinations performed
      within 24 hours of shock onset were enrolled. RESULTS: A total of 163 (50.2%)
      patients with septic shock died during hospitalization. Non-survivors had a
      significantly larger positive net fluid balance within the 24 hour window of
      septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml
      (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid
      balance at 24 hours and eight days post-shock onset respectively were found to
      predict hospital mortality, and the greatest quartile of positive net fluid
      balance at eight days post-shock onset was an independent predictor of hospital
      mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004).
      Survivors were significantly more likely to have mild left ventricular
      dysfunction as evaluated by bedside echocardiography and non-survivors had
      slightly elevated left ventricular ejection fraction, which was also found to be
      an independent predictor of outcome. CONCLUSIONS: Our data confirms the
      importance of fluid balance and cardiac function as outcome predictors in
      patients with septic shock. A clinical trial to determine the optimal
      administration of intravenous fluids to patients with septic shock is needed.

PMID- 24138870
TI  - Hormone replacement therapy and risk of glioma: a nationwide nested case-control
      study.
AB  - AIM: Several studies indicate that use of hormone replacement therapy (HRT) is
      associated with an increased risk of intracranial meningioma, while associations
      between HRT use and risk of other brain tumors have been less explored. We
      investigated the influence of HRT use on the risk of glioma in a nationwide
      setting. METHODS: Using population-based registries we conducted a case-control
      study nested in the Danish female population. We identified all women aged 55-84
      years with a first diagnosis of histologically verified brain glioma during 2000
      2009. Using risk-set sampling, each case was matched on birth year to eight
      population controls. Ever use of HRT was defined as >=2 HRT prescriptions and
      categorized according to type (oestrogens only, combined oestrogen-progestagen
      and progestagen only) and duration of use (<1, >=1 to <5, >=5 to <10, and >=10
      years). We used conditional logistic regression to compute odds ratios (ORs),
      with 95% confidence intervals (CIs), for glioma associated with HRT use,
      adjusting for potential confounders. RESULTS: We identified 658 cases and 4350
      controls. Ever use of HRT was associated with an OR of 0.9 (95% CI: 0.8-1.1) for
      glioma. For long-term use (>=10 years) we found ORs of 1.1 (95% CI: 0.7-1.7) for
      HRT overall, 1.6 (95% CI: 0.9-2.6) for oestrogen only, 0.8 (0.4-1.6) for combined
      oestrogen-progestagen, and 2.2 (0.9-5.5) for progestagen. Tests for trends were
      statistically non-significant in all strata. CONCLUSION: Use of HRT overall was
      not associated with an increased risk of glioma. However, our findings indicate
      that prolonged use of oestrogen only or progestagen may be associated with an
      increased risk of glioma.

PMID- 24138871
TI  - International comparisons of the incidence and mortality of sinonasal cancer.
AB  - BACKGROUND: This paper reviews international patterns in sinonasal cancer
      incidence and mortality in light of changes in exposure to known risk factors.
      Sinonasal tumours are relatively rare, but they have the second highest
      occupational attributable fraction of all types of cancer, with a well
      established link for workers exposed to wood dust. METHODS: Data for a variety of
      countries, mainly in Europe, North America and the Asia-Pacific region, were
      obtained from publicly accessible sources and supplemented with information
      requested from selected cancer registries. Rates were directly age-standardised
      to the World Health Organization Standard Population. RESULTS: The average annual
      incidence of sinonasal cancer was typically between 5 and 10 per million in males
      and between 2 and 5 per million in females between 2004 and 2008. Denmark
      reported the highest rates, with incidence continuing to increase, in contrast to
      trends in other countries which either remained relatively stable, or were
      decreasing slightly. There were significant recent decreases in sinonasal cancer
      mortality rates within two-thirds of the included countries. CONCLUSIONS: Our
      observations are generally consistent with efforts to limit exposure to wood dust
      and other potentially causal substances in the workplace, as well as a reduction
      in the prevalence of smoking in many developed countries. Of concern is that
      occupational and behavioural risks related to sinonasal cancer are likely to
      increase among people in less developed countries into the future. However the
      incentive to intervene in these countries is limited by the lack of accurate and
      reliable cancer data.

PMID- 24138872
TI  - Increased risk and related factors of depression among patients with COPD: a
      population-based cohort study.
AB  - BACKGROUND: Depression is a common and mostly undertreated problem in patients
      with chronic diseases. However, population-based studies on the association
      between chronic obstructive pulmonary disease (COPD) and subsequent depression
      are limited in Asian populations. This study evaluated the incidence and risk
      factors of depression for patients with COPD in Taiwan. METHODS: Using the claims
      data from the National Health Insurance of Taiwan, we identified 38,010 COPD
      patients newly diagnosed in 2000-2004 and 38,010 subjects without COPD frequency,
      matched by sex, age and index date. The incidence rate and hazard ratio for
      depression were estimated by the end of 2008. RESULTS: The incidence rate of
      depression was 1.88 folds higher in the COPD cohort than in the non-COPD cohort
      (12.2 versus 6.47 per 1,000 person-years, p < 0.0001). The depression risk was
      the greatest within the first year following COPD diagnosis and tended to decline
      with follow-up time. Among COPD patients, multivariate analysis showed that
      younger women and low-income patients were at higher risk of depression.
      Hospitalization and comorbidities such as hypertension, arthritis, cancer, and
      heart disease were also significant predictors for depression risk. CONCLUSION:
      This population-based cohort study demonstrated a strong relationship between
      COPD and subsequent depression. These findings could assist healthcare providers
      to pinpoint individuals with a higher predisposition to having depression, which
      could then facilitate the provision of culturally appropriate rehabilitation
      within the first year after the diagnosis of COPD.

PMID- 24138873
TI  - Peri-ictal water drinking and other ictal vegetative symptoms: Localizing and
      lateralizing the epileptogenic zone in temporal lobe epilepsy? Two case reports
      and review of the literature.
AB  - Peri-ictal behavior disorders can be helpful in localizing and lateralizing
      seizure onset in partial epilepsies, especially those originating in the temporal
      lobe. In this paper, we present the case of two right-handed women aged 36 and 42
      years who presented with partial seizures of mesial temporal type. Both of the
      patients had drug resistant epilepsy and undergone presurgical evaluation tests
      including brain magnetic resonance imaging, video-EEG monitoring and
      neuropsychological testing. The two patients had hippocampal sclerosis in the
      right temporal lobe and exhibited PIWD behavior concomitant with right temporal
      lobe discharges documented during video-EEG recordings. Anterior temporal
      lobectomy was performed in one case with an excellent outcome after surgery. The
      patient was free of seizures at 3 years follow-up. We reviewed other publications
      of peri-ictal autonomic symptoms considered to have a lateralizing significance,
      such as peri-ictal vomiting, urinary urge, ictal pilo-erection. Clinicians should
      search for these symptoms, even if not spontaneously reported by the patient,
      because they are often under-estimated, both by the patients themselves and by
      physicians. Additionally, patients with lateralizing auras during seizures have a
      significantly better outcome after epilepsy surgery than those without
      lateralizing features. 

PMID- 24138874
TI  - Placental findings in late-onset SGA births without Doppler signs of placental
      insufficiency.
AB  - OBJECTIVES: To describe placental pathological findings in late-onset small-for
      gestational age (SGA) births for which Doppler signs of placental insufficiency
      are lacking. METHODS: A series of placentas were evaluated from singleton
      pregnancies of SGA births (birth weight below the 10th percentile) delivered
      after 34 weeks with normal umbilical artery Doppler (pulsatility index below the
      95th percentile), that were matched by gestational age with adequate-for
      gestational age (AGA) controls. Using a hierarchical and standardized system,
      placental lesions were classified histologically as consequence of maternal
      underperfusion, fetal underperfusion or inflammation. RESULTS: A total of 284
      placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142)
      of the placentas had weights below the 3rd percentile for GA while it was a 9.9%
      (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were
      free of histological abnormalities, while it was 74.6% (106/142) in the AGA group
      (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161
      lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and
      inflammation in 20.5% (33/161). DISCUSSION: In most placentas of term SGA
      neonates with normal UA Doppler histological abnormalities secondary to maternal
      underperfusion prevail, reflecting latent insufficiency in uteroplacental blood
      supply. This is consistent with the higher risk of adverse perinatal outcome
      reported in this population and underscores a need for new markers of placental
      disease. CONCLUSIONS: A significant proportion of late-onset SGA births with
      normal umbilical artery Doppler may still be explained by placental
      insufficiency.

PMID- 24138875
TI  - An element of life: competition for zinc in host-pathogen interaction.
AB  - Zinc homeostasis plays a plethora of different roles in the immune response. In
      this issue of Immunity, Vignesh et al. (2013) demonstrate that stimulation of
      macrophages with GM-CSF deprives intracellular Histoplasma capsulatum of zinc,
      improving pathogen clearance. 

PMID- 24138876
TI  - What on "irf" is this gene 4? Irf4 transcription-factor-dependent dendritic cells
      are required for T helper 2 cell responses in murine skin.
AB  - Interferon regulatory factors play an important role in the transcriptional
      regulation of immunity. In this issue of Immunity, Kumamoto et al. (2013) and Gao
      et al. (2013) identify an Irf4-dependent migratory dendritic cell subset required
      for T helper 2 cell polarization following cutaneous challenge. 

PMID- 24138877
TI  - IL-9 by INFERence.
AB  - Despite the discovery of the cytokine over 20 years ago, the relevant biological
      sources of interleukin-9 (IL-9) have remained a mystery. In this issue of
      Immunity, Licona-Limon et al. (2013) use a newly generated reporter mouse to
      demonstrate a role for IL-9-secreting T cells in helminthic parasite immunity. 

PMID- 24138878
TI  - Blood Tfh cells come with colors.
AB  - Blood CXCR5+ CD4+ T cells share phenotypic and functional similarities with T
      follicular helper cells. Studies by He et al. (2013) and Locci et al. (2013) in
      this issue of Immunity provide insight into their ontogeny and functionally
      distinct subsets.

PMID- 24138879
TI  - A "big data" view of the tumor "immunome".
AB  - Tumors are complex masses containing not just neoplastic cells but also stromal
      cells, neovasculature, and a gamut of immune cells. In this issue, Bindea et al.
      (2013) identify a surprising new "immune landscape" associated with prolonged
      disease-free survival. 

PMID- 24138880
TI  - Systemic effects of inflammation on health during chronic HIV infection.
AB  - Combination antiretroviral therapy for HIV infection improves immune function and
      eliminates the risk of AIDS-related complications but does not restore full
      health. HIV-infected adults have excess risk of cardiovascular, liver, kidney,
      bone, and neurologic diseases. Many markers of inflammation are elevated in HIV
      disease and strongly predictive of the risk of morbidity and mortality. A
      conceptual model has emerged to explain this syndrome of diseases where HIV
      mediated destruction of gut mucosa leads to local and systemic inflammation.
      Translocated microbial products then pass through the liver, contributing to
      hepatic damage, impaired microbial clearance, and impaired protein synthesis.
      Chronic activation of monocytes and altered liver protein synthesis subsequently
      contribute to a hypercoagulable state. The combined effect of systemic
      inflammation and excess clotting on tissue function leads to end-organ disease.
      Multiple therapeutic interventions designed to reverse these pathways are now
      being tested in the clinic. It is likely that knowledge gained on how
      inflammation affects health in HIV disease could have implications for our
      understanding of other chronic inflammatory diseases and the biology of aging. 

PMID- 24138881
TI  - Granulocyte macrophage-colony stimulating factor induced Zn sequestration
      enhances macrophage superoxide and limits intracellular pathogen survival.
AB  - Macrophages possess numerous mechanisms to combat microbial invasion, including
      sequestration of essential nutrients, like zinc (Zn). The pleiotropic cytokine
      granulocyte macrophage-colony stimulating factor (GM-CSF) enhances antimicrobial
      defenses against intracellular pathogens such as Histoplasma capsulatum, but its
      mode of action remains elusive. We have found that GM-CSF-activated infected
      macrophages sequestered labile Zn by inducing binding to metallothioneins (MTs)
      in a STAT3 and STAT5 transcription-factor-dependent manner. GM-CSF upregulated
      expression of Zn exporters, Slc30a4 and Slc30a7; the metal was shuttled away from
      phagosomes and into the Golgi apparatus. This distinctive Zn sequestration
      strategy elevated phagosomal H+ channel function and triggered reactive oxygen
      species generation by NADPH oxidase. Consequently, H. capsulatum was selectively
      deprived of Zn, thereby halting replication and fostering fungal clearance. GM
      CSF mediated Zn sequestration via MTs in vitro and in vivo in mice and in human
      macrophages. These findings illuminate a GM-CSF-induced Zn-sequestration network
      that drives phagocyte antimicrobial effector function.

PMID- 24138882
TI  - Processing of human toll-like receptor 7 by furin-like proprotein convertases is
      required for its accumulation and activity in endosomes.
AB  - Toll-like receptor 7 (TLR7) triggers antiviral immune responses by recognizing
      viral single-stranded RNA in endosomes, but the biosynthetic pathway of human
      TLR7 (hTLR7) remains unclear. Here, we show that hTLR7 is proteolytically
      processed and that the C-terminal fragment selectively accumulates in endocytic
      compartments. hTLR7 processing occurred at neutral pH and was dependent on furin
      like proprotein convertases (PCs). Furthermore, TLR7 processing was required for
      its functional response to TLR7 agonists such as R837 or influenza virus.
      Notably, proinflammatory and differentiation stimuli increased the expression of
      furin-like PCs in immune cells, suggesting a positive feedback mechanism for TLR7
      processing during infection. Because self-RNA can under certain conditions
      activate TLR7 and trigger autoimmunity, our results identify furin-like PCs as a
      possible target to attenuate TLR7-dependent autoimmunity and other immune
      pathologies. 

PMID- 24138883
TI  - Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection.
AB  - Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL
      13, drive the characteristic features of immunity against parasitic worms and
      allergens. Whether IL-9 serves an essential role in the initiation of host
      protective responses is controversial, and the importance of IL-9- versus IL-4
      producing CD4+ effector T cells in type 2 immunity is incompletely defined.
      Herein, we generated IL-9-deficient and IL-9-fluorescent reporter mice that
      demonstrated an essential role for this cytokine in the early type 2 immunity
      against Nippostrongylus brasiliensis. Whereas T helper 9 (Th9) cells and type 2
      innate lymphoid cells (ILC2s) were major sources of infection-induced IL-9
      production, the adoptive transfer of Th9 cells, but not Th2 cells, caused rapid
      worm expulsion, marked basophilia, and increased mast cell numbers in Rag2
      deficient hosts. Taken together, our data show a critical and nonredundant role
      for Th9 cells and IL-9 in host-protective type 2 immunity against parasitic worm
      infection.

PMID- 24138884
TI  - Circulating precursor CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells indicate Tfh cell
      activity and promote antibody responses upon antigen reexposure.
AB  - Follicular B helper T (Tfh) cells support high affinity and long-term antibody
      responses. Here we found that within circulating CXCR5+ CD4+ T cells in humans
      and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype,
      whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating
      CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid
      organs and correlated with clinical indices in autoimmune diseases. Thus the
      CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody
      responses during infection or vaccination and pathogenic antibody responses in
      autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD
      1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating
      CXCR5+ helper T cells are primarily generated before germinal centers. Upon
      antigen reencounter, CCR7(lo)PD-1(hi) CXCR5+ precursors rapidly differentiate
      into mature Tfh cells to promote antibody responses. Therefore, circulating
      CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells are generated during active Tfh
      differentiation and represent a new mechanism of immunological early memory.

PMID- 24138885
TI  - Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape
      in human cancer.
AB  - The complex interactions between tumors and their microenvironment remain to be
      elucidated. Combining large-scale approaches, we examined the spatio-temporal
      dynamics of 28 different immune cell types (immunome) infiltrating tumors. We
      found that the immune infiltrate composition changed at each tumor stage and that
      particular cells had a major impact on survival. Densities of T follicular helper
      (Tfh) cells and innate cells increased, whereas most T cell densities decreased
      along with tumor progression. The number of B cells, which are key players in the
      core immune network and are associated with prolonged survival, increased at a
      late stage and showed a dual effect on recurrence and tumor progression. The
      immune control relevance was demonstrated in three endoscopic orthotopic colon
      cancer mouse models. Genomic instability of the chemokine CXCL13 was a mechanism
      associated with Tfh and B cell infiltration. CXCL13 and IL21 were pivotal factors
      for the Tfh/B cell axis correlating with survival. This integrative study reveals
      the immune landscape in human colorectal cancer and the major hallmarks of the
      microenvironment associated with tumor progression and recurrence. 

PMID- 24138886
TI  - A Life Cycle Assessment of integrated dairy farm-greenhouse systems in British
      Columbia.
AB  - The purpose of this study was to evaluate the anticipated environmental benefits
      from integrating a dairy farm and a greenhouse; the integration is based on
      anaerobic digestion of manures to produce biogas energy, biogenic CO2, and
      digested slurry. A full Life Cycle Assessment (LCA) has been conducted on six
      modeled cases applicable in British Columbia, to evaluate non-renewable energy
      consumption, climate change, acidification, eutrophication, respiratory effects
      and human toxicity. Compared to conventional practice, an integrated system has
      the potential to nearly halve eutrophication and respiratory effects caused by
      inorganic emissions and to reduce non-renewable energy consumption, climate
      change, and acidification by 65-90%, while respiratory effects caused by organic
      emissions become negative as co-products substitute for other materials. Co
      digestion of other livestock manures, greenhouse plant waste, or food and food
      processing waste with dairy manure can further improve the performance of the
      integrated system. 

PMID- 24138887
TI  - "Earthly Angels"? A qualitative study of the domiciliary care worker role in
      meeting the needs of families caring for those dying at home.
AB  - OBJECTIVE: Relatively little attention has been paid to optimum ways in which
      community-based care services can support family caregivers in the context of end
      of-life care at home. This paper addresses such concerns by focusing on the
      services provided by domiciliary care workers. METHOD: We draw on qualitative
      formal interviews with 42 family members, 1 patient, and 6 staff, as well as
      observation sessions and informal interviews with additional family caregivers
      and staff, to examine the aspects of domiciliary care perceived to be of most
      value. In particular, we compare and contrast family caregivers' experience of
      the support provided by generic domiciliary care workers with that of a team of
      specialist domiciliary care workers. RESULTS: Our findings show that specialist
      domiciliary care workers had sufficient time and expertise to meet family
      caregivers' physical and emotional needs in sensitive, proactive, and family
      centered ways, and that these attributes were not so prominent in the services
      received from generic domiciliary care workers. SIGNIFICANCE OF RESULTS: The
      availability to families of targeted support from an appropriately trained and
      carefully monitored team of specialist domiciliary care workers, able to operate
      flexibly and with staff consistency, appears to be an important foundation on
      which to build greater confidence in the reality of a good death at home.

PMID- 24138889
TI  - Acute small bowel obstruction due to internal herniation through the Foramen of
      Winslow: CT diagnosis and laparoscopic treatment.

PMID- 24138888
TI  - Umbelliferone beta-D-galactopyranoside from Aegle marmelos (L.) corr. an
      ethnomedicinal plant with antidiabetic, antihyperlipidemic and antioxidative
      activity.
AB  - BACKGROUND: Aegle marmelos (L.) Corr. (Rutaceae), commonly known as bael, is used
      to treat fevers, abdomen pain, palpitation of the heart, urinary troubles,
      melancholia, anorexia, dyspepsia, diabetes and diarrhea in Indian traditional
      systems of medicine. The object of the present study was to evaluate the
      antidiabetic, antihyperlipidemic and antioxidant oxidative stress of
      umbelliferone beta-D-galactopyranoside (UFG) from stem bark of Aegle marmelos
      Correa. in STZ (streptozotocin) induced diabetic rat. METHODS: Diabetes was
      induced in rat by single intraperitoneal injection of STZ (60 mg/kg). The rat was
      divided into the following groups; I - normal control, II - diabetic control, III
      - UFG (10 mg/kg), IV - UFG (20 mg/kg), V - UFG (40 mg/kg), VI - Glibenclamide (10
      mg/kg, p.o., once a daily dose). Diabetes was measured by change the level blood
      glucose, plasma insulin and the oxidative stress were assessed in the liver by
      estimation of the level of antioxidant markers i.e. superoxide dismutase (SOD),
      glutathione peroxidase (GPx), catalase (CAT) and Malondialdehyde (MDA) and
      antihyperlipidemic effect was measured by estimation of total cholesterol,
      triglycerides, LDL (low density lipoprotein) cholesterol, HDL (high density
      lipoprotein) cholesterol, VLDL (very low density lipoprotein) cholesterol.
      However in a study, the increased body weight was observed and utilization of
      glucose was in the oral glucose tolerance test. RESULT: Daily oral administration
      of different dose of UFG for 28 days showed significantly (P < 0.001) decreased
      in fasting blood glucose level and improve plasma insulin level as compared to
      the diabetic control group. Also it significantly (P < 0.001) decreased the level
      of glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate and
      increased the level of hexokinase. UFG treatment decreased liver MDA and
      increased the level of SOD, GPx and CAT. UFG treatment of lipids it's increased
      the level of cholesterol, triglycerides, VLDL, LDL cholesterol and decreased the
      level of HDL cholesterol. Histologically, inflammatory cell in blood vessels,
      intercalated disc, fat degeneration and focal necrosis observed in diabetic rat
      organ but was less obvious in UFG treated groups. The mechanism of action of UFG
      may be due to the increased level of pancreatic insulin secretion and effect on
      the antioxidant marker. CONCLUSION: UFG posses an antidiabetic, antioxidant and
      antihyperlipidemic effect on the STZ induced diabetic rat. Hence it could be the
      better choice to cure the diabetes.

PMID- 24138890
TI  - Response to the commentary 'Early clean intermittent catheterization may not
      prevent dimercaptosuccinic acid renal scan abnormalities in children with spinal
      dysraphism'.

PMID- 24138891
TI  - Triple therapy in idiopathic pulmonary fibrosis.

PMID- 24138892
TI  - The Harvard angiogenesis story.
AB  - I shall discuss the work of researchers at Harvard Medical School who came
      together in the early 1990s. Scattered across various Harvard-affiliated
      hospitals and research centers, these individuals were unified by their interest
      in ocular neovascularization. Together and separately, they investigated models
      of ocular neovascularization, exploring tumor angiogenesis in eye development and
      disease. 

PMID- 24138893
TI  - Current management of Coats disease.
AB  - Since its original description in 1908, Coats disease has been recognized as an
      idiopathic cause of severe vision loss with a remarkable diversity in clinical
      presentation and morphology. Key clinical and imaging variables are helpful in
      differentiating Coats disease from life-threatening malignancies, and proper
      management revolves around a thorough knowledge of the differential diagnosis.
      Despite significant advancement in scientific understanding of the disease
      process and clinical spectrum, the underlying etiology remains obscure, and both
      primary and secondary forms are recognized. With the development of anti-VEGF
      therapy, vitreoretinal specialists have a new, effective adjunct to the clinical
      management of exudates, macular edema, and serous retinal detachment. We
      highlight the history, diagnostic challenges, evolving clinical spectrum, and
      current management of Coats disease.

PMID- 24138894
TI  - Application of anterior segment optical coherence tomography in glaucoma.
AB  - Optical coherence tomography (OCT) is a cross-sectional, three-dimensional, high
      resolution imaging modality that uses low coherence interferometry to achieve
      axial resolution in the range of 3-20 MUm. Two OCT platforms have been developed:
      time domain (TD-OCT) and spectral (or Fourier) domain (SD/FD-OCT). Visante
      anterior segment OCT (Carl Zeiss Meditec) is a TD-OCT widely used for anterior
      segment imaging. The SD-OCT systems with both posterior and anterior segment
      imaging capabilities include the RTVue, iVue (Optovue), the Cirrus (Carl Zeiss
      Meditec), and the Spectralis (Heidelberg Engineering, Inc.). Each of the SD-OCTs
      has a wavelength in the range of 820-879 nm. Anterior segment OCT is a non
      contact method providing high resolution tomographic cross-sectional imaging of
      anterior segment structures. Anterior segment OCT provides qualitative and
      quantitative assessment of the anterior segment structures important to the
      pathogenesis and the anatomical variations of glaucoma, and the approach to and
      success of treatment. We summarize the clinical applications of anterior segment
      OCT in glaucoma. 

PMID- 24138895
TI  - Giant retinal tears.
AB  - A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that
      extends circumferentially around the retina for three or more clock hours in the
      presence of a posteriorly detached vitreous. Its incidence in large population
      based studies has been estimated as 1.5% of rhegmatogenous retinal detachments,
      with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are
      idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each
      being causative in decreasing frequency. The vast majority of GRTs are currently
      managed with a pars plana vitrectomy; the use of adjunctive circumferential
      scleral buckling is debated, but no studies have shown a clear anatomical or
      visual advantage with its use. Similarly, silicone oil tamponade does not
      influence long-term outcomes when compared with gas. Primary and final retinal
      reattachment rates are achieved in 88% and 95% of patients, respectively. Even
      when the retina remains attached, however, visual recovery may be limited.
      Furthermore, fellow eyes of patients with a GRT are at higher risk of developing
      retinal tears and retinal detachment. Prophylactic treatment under these
      circumstances may be considered but there is no firm evidence of its efficacy at
      the present time. 

PMID- 24138896
TI  - Induction of micronucleus of Oreochromis niloticus exposed to waters from the
      Cubatao do Sul River, southern Brazil.
AB  - In an effort to characterize the pollution of surface waters by potentially
      genotoxic agents, this study aimed at assessing the frequency of micronucleated
      (MN) erythrocytes of the fish species, Oreochromis niloticus, from the Cubatao do
      Sul River. This river is the source of drinking water for the region of
      Florianopolis, capital of Santa Catarina State, Brazil. Negative control fish
      showed low frequency of MN, ranging between 0.490/00 and 0.900/00. Positive
      control (potassium dichromate 2.5 mg/L) organisms showed high MN frequency (16.82
      17.250/00). The MN frequency increased along the river (Site 1--1.240/00 winter
      2011; Site 4--9.760/00 summer 2011). Based on the observation of elevated MN
      erythrocytes frequency in O. niloticus exposed to water samples from along the
      river course, we conclude that the complex environmental mixtures of water from
      the Cubatao do Sul River have genotoxic potential. This genotoxicity most likely
      originated from agricultural runoff and domestic effluents released without
      treatment, based on the evidence from literature data and a survey in the region.
      This study provides a scientific basis for future studies regarding the
      genotoxicity of complex environmental mixtures in natural environments.

PMID- 24138897
TI  - Biodecolorization of Reactive Black-5 by a metal and salt tolerant bacterial
      strain Pseudomonas sp. RA20 isolated from Paharang drain effluents in Pakistan.
AB  - Discharge of untreated azo dyes contaminated textile wastewater into soil and
      water bodies causes severe contamination. The present study was conducted to
      isolate dye degrading bacterial strains from a textile industry wastewater
      carrying drain in the neighborhood of Faisalabad, Pakistan. Seventy six bacterial
      strains were initially isolated and was screened using liquid mineral salts
      medium spiked with Reactive Black-5 azo dye. The strain RA20 was found to be the
      most efficient azo dye degrading bacterial isolate and was identified by
      amplifying and sequencing its 16S rRNA. Analysis indicated that this strain
      belonged to genus Pseudomonas and was designated as Pseudomonas sp. RA20. It had
      the highest decolorization activity at pH 8 and 25  degrees C incubation
      temperature under static conditions using yeast extract as an additional C
      source. This strain was also effective in decolorizing structurally related other
      reactive dyes including Reactive Orange 16, Reactive Yellow 2 and Reactive Red
      120 but with varying efficacy. RA20 decolorized Reactive Black-5 significantly in
      the presence of up to 30 g L-1 NaCl; however, the decolorization rate was
      significantly (p<=0.05) reduced beyond this salt concentration. Moreover, this
      bacterial strain also exhibited moderate tolerance to different heavy metals
      including zinc (Zn), cadmium (Cd), chromium (Cr), lead (Pb) and copper (Cu). RA20
      also decolorized Reactive Black-5 in the presence of a mixture of the selected
      heavy metals depending upon their concentrations. This study highlights the
      importance of Pseudomonas sp. RA20 as a prospective biological resource for
      bioremediation of water and soils contaminated with azo dyes.

PMID- 24138898
TI  - Avermectin induced liver injury in pigeon: mechanisms of apoptosis and oxidative
      stress.
AB  - Extensive use of avermectin (AVM) can result in environment pollution, and it is
      important to evaluate the potential impact this antibiotic has on ecological
      systems. Few published literatures have discussed the liver injury mechanisms
      induced by AVM on birds. In this study, pigeons were exposed to feed containing
      AVM (0, 20, 40 and 60 mg/kg diet) for 30, 60, 90 days respectively. The results
      showed that AVM increased the number of apoptosis and the expression level of
      caspase-3, 8, fas mRNA in the liver of pigeons. Ultrastructural alterations,
      including mitochondrial damage and chromatin aggregation, become severe with
      increase exposure dose. Exposure to AVM induced significant changes in
      antioxidant enzyme {superoxide dismutase (SOD) and glutathione peroxidase (GSH
      Px)} activities and malondialdehyde (MDA) content, augmented protein carbonyl
      (PCO) content and DNA-protein crosslink (DPC) coefficient, in a concentration
      dependent manner in the liver of pigeons. Our results show that AVM has toxic
      effect in pigeon liver, and the mechanism of injury caused by AVM is closely
      related to apoptosis and oxidative stress.

PMID- 24138899
TI  - Association of food-hygiene practices and diarrhea prevalence among Indonesian
      young children from low socioeconomic urban areas.
AB  - BACKGROUND: Information on the part that poor food-hygiene practices play a role
      in the development of diarrhea in low socioeconomic urban communities is lacking.
      This study was therefore aimed at assessing the contribution of food-hygiene
      practice to the prevalence of diarrhea among Indonesian children. METHODS: A
      cross-sectional study was conducted among 274 randomly selected children aged 12
      59 months in selected low socioeconomic urban areas of East Jakarta. The
      prevalence of diarrhea was assessed from 7-day records on frequency and
      consistency of the child's defecation pattern. Food-hygiene practices including
      mother's and child's hand washing, food preparation, cleanliness of utensils,
      water source and safe drinking water, habits of buying cooked food, child's
      bottle feeding hygiene, and housing and environmental condition were collected
      through home visit interviews and observations by fieldworkers. Thirty-six
      practices were scored and classified into poor (median and below) and better
      (above median) food-hygiene practices. Nutritional status of children, defined
      anthropometrically, was measured through height and weight. RESULTS: Among the
      individual food-hygiene practices, children living in a house with less dirty
      sewage had a significantly lower diarrhea prevalence compared to those who did
      not [adjusted odds ratio (OR) 0.16, 95% confidence interval (CI) = 0.03-0.73].
      The overall food-hygiene practice score was not significantly associated with
      diarrhea in the total group, but it was in children aged < 2 years (adjusted OR
      4.55, 95% CI = 1.08-19.1). CONCLUSIONS: Overall poor mother's food-hygiene
      practices did not contribute to the occurrence of diarrhea in Indonesian
      children. However, among children < 2 years from low socioeconomic urban areas
      they were associated with more diarrhea.

PMID- 24138900
TI  - Oral and dental health in Huntington's disease - an observational study.
AB  - BACKGROUND: Only a few case reports and case series dealing with oral and dental
      health care are available in literature until now. The aim of the present pilot
      study was to determine the status of dental health in comparison to matched
      controls and to heighten the neurologists' and dentists' awareness of the oral
      aspects of the disease. METHODS: 42 Huntington's disease (HD) participants were
      scored according to the Unified Huntington's Disease Rating Scale. The dental
      status was assessed by using the well established score for decayed, missing, and
      filled teeth (DMFT) and the dental plaque score (Silness-Loe plaque index).
      RESULTS: Compared to controls HD participants showed significantly more decayed
      teeth and more plaques in both plaque indices. A higher motor impairment and a
      lower functional status of the patients lead to a worsening in dental status.
      CONCLUSION: Possible reasons for our findings are discussed. Apart from local
      oral complications general complications may also occur. Thus, as a consequence,
      we would encourage patients, caregivers, neurologists, and the dentists to ensure
      regular preventive dental examinations and dental treatments of individuals with
      Huntington's disease even in the premanifest stage of this disease.

PMID- 24138902
TI  - Availability of EGFR mutation status at first oncology consultation for advanced
      non-squamous non-small cell lung cancer patients. A pilot experience from the
      Christie.

PMID- 24138901
TI  - alpha1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical
      astrocytes in awake, behaving mice.
AB  - Astrocyte Ca2+ signals in awake behaving mice are widespread, coordinated and
      differ fundamentally from the locally restricted Ca2+ transients observed ex vivo
      and in anesthetized animals. Here we show that the synchronized release of
      norepinephrine (NE) from locus coeruleus (LC) projections throughout the cerebral
      cortex mediate long-ranging Ca2+ signals by activation of astrocytic alpha1
      adrenergic receptors. When LC output was triggered by either physiological
      sensory (whisker) stimulation or an air-puff startle response, astrocytes
      responded with fast Ca2+ transients that encompassed the entire imaged field
      (positioned over either frontal or parietal cortex). The application of
      adrenergic inhibitors, including alpha1-adrenergic antagonist prazosin, potently
      suppressed both evoked, as well as the frequently observed spontaneous astroglial
      Ca2+ signals. The LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4), which reduced cortical NE content by >90%, prevented
      nearly all astrocytic Ca2+ signals in awake mice. The observations indicate that
      in adult, unanesthetized mice, astrocytes do not respond directly to
      glutamatergic signaling evoked by sensory stimulation. Instead astrocytes appear
      to be the primary target for NE, with astrocytic Ca2+ signaling being triggered
      by the alpha1-adrenergic receptor. In turn, astrocytes may coordinate the broad
      effects of neuromodulators on neuronal activity.

PMID- 24138903
TI  - Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin
      enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells.
AB  - OBJECTIVES: Gefitinib, a quinazoline-derived tyrosine kinase inhibitor, has anti
      tumor activity in vivo and in vitro. Human MutS homologue-2 (MSH2) plays a
      central role in promoting genetic stability by correcting DNA replication errors.
      The present study investigated the effects of p38 mitogen-activated protein
      kinase (MAPK) signal on gefitinib-induced MSH2 expression in two human non-small
      cell lung squamous cancer cell lines. MATERIALS AND METHODS: After the gefitinib
      treatment, the expressions of MSH2 mRNA were determined by real-time PCR and RT
      PCR analysis. Protein levels of MSH2, phospho-MKK3/6, phospho-p38 MAPK were
      determined by Western blot analysis. We used specific MSH2, and p38 MAPK small
      interfering RNA to examine the role of p38 MAPK-MSH2 signal in regulating the
      chemosensitivity of gefitinib. Cell viability was assessed by MTS assay, trypan
      blue exclusion, and colony-forming ability assay. RESULTS: Exposure of gefitinib
      increased MSH2 protein and mRNA levels, which was accompanied by MKK3/6-p38 MAPK
      activation in H520 and H1703 cells. Moreover, blocking p38 MAPK activation by
      SB202190 significantly decreased gefitinib-induced MSH2 expression by increasing
      mRNA and protein instability. In contrast, enhancing p38 activation using
      constitutively active MKK6 (MKK6E) increased MSH2 protein and mRNA levels.
      Specific inhibition of MSH2 expression by siRNA enhanced gefitinib-induced
      cytotoxicity. Metformin, an anti-diabetic drug, might reduce cancer risk. In
      human lung squamous cancer cells, metformin decreased gefitinib-induced MSH2
      expression and augmented the cytotoxic effect and growth inhibition by gefitinib.
      Transient expression of MKK6E or HA-p38 MAPK vector could abrogate metformin and
      gefitinib-induced synergistic cytotoxic effect in H520 and H1703 cells.
      CONCLUSION: Together, down-regulation of MSH2 expression can be a possible
      strategy to enhance the sensitivity of gefitinib to human lung squamous cancer
      cells.

PMID- 24138904
TI  - The effect of fractionation in stereotactic body radiation therapy using the
      linear quadratic mode. In regard to Yang et al.

PMID- 24138905
TI  - In reply to Healy.

PMID- 24138906
TI  - In reply to Sharma et al.

PMID- 24138907
TI  - Evaluation of high ipsilateral subventricular zone radiation therapy dose in
      glioblastoma: a pooled analysis. In regard to Lee et al.

PMID- 24138908
TI  - A population-based study of the fractionation of postlumpectomy breast radiation
      therapy. In regard to Ashworth et al.

PMID- 24138909
TI  - Effects of treatment duration during concomitant chemoradiation therapy for
      cervical cancer. In regard to Shaverdian et al.

PMID- 24138910
TI  - In Reply to Berrang et al.

PMID- 24138911
TI  - Whole-pelvic radiation therapy in the context of hypofractionation for high-risk
      prostate cancer patients: a step forward. In regard to Kaidar-Person et al.

PMID- 24138912
TI  - Patient-reported outcomes in patients with nonmelanomatous skin cancers of the
      face treated with orthovoltage radiation therapy: a cross-sectional survey.

PMID- 24138913
TI  - Conventional versus automated implantation of loose seeds in prostate
      brachytherapy: analysis of dosimetric and clinical results.
AB  - PURPOSE: To review the clinical outcome of I-125 permanent prostate brachytherapy
      (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2
      techniques of loose-seed implantation. METHODS AND MATERIALS: 574 consecutive
      patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer
      between 2000 and 2008. Two successive techniques were used: conventional
      implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST
      system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED)
      survival results were reported and compared for the 2 techniques. Univariate and
      multivariate analysis researched independent predictors for bNED survival.
      RESULTS: 419 (73%) and 155 (27%) patients with low-risk and intermediate-risk
      disease, respectively, were treated (median follow-up time, 69.3 months). The 60
      month bNED survival rates were 95.2% and 85.7%, respectively, for patients with
      low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients
      treated with automated implantation had worse bNED survival rates than did those
      treated with conventional implantation (P<.0001). By day 30, patients treated
      with automated implantation showed lower values of dose delivered to 90% of
      prostate volume (D90) and volume of prostate receiving 100% of prescribed dose
      (V100). In multivariate analysis, implantation technique, Gleason score, and V100
      on day 30 were independent predictors of recurrence-free status. Grade 3
      urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort,
      respectively, with no significant differences between the 2 techniques. No grade
      3 proctitis was observed. CONCLUSION: Satisfactory 60-month bNED survival rates
      (93.1%) and acceptable toxicity (grade 3 urethritis<3%) were achieved by loose
      seed implantation. Automated implantation was associated with worse dosimetric
      and bNED survival outcomes.

PMID- 24138914
TI  - Individualized prediction of overall survival after postoperative radiation
      therapy in patients with early-stage cervical cancer: a Korean Radiation Oncology
      Group study (KROG 13-03).
AB  - PURPOSE: A nomogram is a predictive statistical model that generates the
      continuous probability of a clinical event such as death or recurrence. The aim
      of the study was to construct a nomogram to predict 5-year overall survival after
      postoperative radiation therapy for stage IB to IIA cervical cancer. METHODS AND
      MATERIALS: The clinical data from 1702 patients with early-stage cervical cancer,
      treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop
      a prediction nomogram based on the Cox proportional hazards model. Demographic,
      clinical, and pathologic variables were included and analyzed to formulate the
      nomogram. The discrimination and calibration power of the model was measured
      using a concordance index (c-index) and calibration curve. RESULTS: The median
      follow-up period for surviving patients was 75.6 months, and the 5-year overall
      survival probability was 87.1%. The final model was constructed using the
      following variables: age, number of positive pelvic lymph nodes, parametrial
      invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The
      nomogram predicted the 5-year overall survival with a c-index of 0.69, which was
      superior to the predictive power of the International Federation of Gynecology
      and Obstetrics (FIGO) staging system (c-index of 0.54). CONCLUSIONS: A survival
      predicting nomogram that offers an accurate level of prediction and
      discrimination was developed based on a large multi-center study. The model may
      be more useful than the FIGO staging system for counseling individual patients
      regarding prognosis.

PMID- 24138915
TI  - Administration of concurrent vaginal brachytherapy during chemotherapy for
      treatment of endometrial cancer.
AB  - PURPOSE: To evaluate the tolerability and toxicity of administering vaginal
      brachytherapy (VB) concurrently during chemotherapy compared with the sequential
      approach for patients with endometrial cancer. METHODS AND MATERIALS: A
      retrospective analysis of 372 surgically staged patients with endometrial cancer
      American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant
      postoperative radiation therapy (RT) at our institution from 2001 to 2012 was
      conducted. All patients received VB+external beam RT (EBRT)+6 cycles of adjuvant
      carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy
      (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45
      Gy delivered with 3-dimensional or intensity modulated RT techniques.
      Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were
      assessed by Common Toxicity Criteria (CTC) and compared between sequential and
      concurrent chemotherapy and VB schedules. RESULTS: Among patients who received RT
      and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched
      between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%)
      were treated with VB during the first 3 cycles of chemotherapy, with a weekly
      application on nonchemotherapy days, and received the EBRT portion in a
      sandwiched fashion. Patients treated with VB during chemotherapy had a decreased
      overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02)
      and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities
      in comparison with the patients treated with VB and chemotherapy in a sequential
      manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero.
      CONCLUSIONS: VB during chemotherapy is well tolerated, decreases overall
      treatment time, and does not render more toxicity than the sequential regimen.

PMID- 24138916
TI  - Two-year and lifetime cost-effectiveness of intensity modulated radiation therapy
      versus 3-dimensional conformal radiation therapy for head-and-neck cancer.
AB  - PURPOSE: To assess the cost-effectiveness of intensity modulated radiation
      therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) in the
      treatment of head-and neck-cancer (HNC). METHODS AND MATERIALS: We used a Markov
      model to simulate radiation therapy-induced xerostomia and dysphagia in a
      hypothetical cohort of 65-year-old HNC patients. Model input parameters were
      derived from PARSPORT (CRUK/03/005) patient-level trial data and quality-of-life
      and Medicare cost data from published literature. We calculated average
      incremental cost-effectiveness ratios (ICERs) from the US health care perspective
      as cost per quality-adjusted life-year (QALY) gained and compared our ICERs with
      current cost-effectiveness standards whereby treatment comparators less than
      $50,000 per QALY gained are considered cost-effective. RESULTS: In the first 2
      years after initial treatment, IMRT is not cost-effective compared with 3D-CRT,
      given an average ICER of $101,100 per QALY gained. However, over 15 years
      (remaining lifetime on the basis of average life expectancy of a 65-year-old),
      IMRT is more cost-effective at $34,523 per QALY gained. CONCLUSION: Although HNC
      patients receiving IMRT will likely experience reduced xerostomia and dysphagia
      symptoms, the small quality-of-life benefit associated with IMRT is not cost
      effective in the short term but may be cost-effective over a patient's lifetime,
      assuming benefits persist over time and patients are healthy and likely to live
      for a sustained period. Additional data quantifying the long-term benefits of
      IMRT, however, are needed.

PMID- 24138917
TI  - Management of male breast cancer in the United States: a surveillance,
      epidemiology and end results analysis.
AB  - PURPOSE: To analyze the stage-specific management of male breast cancer (MBC)
      with surgery and radiation therapy (RT) and relate them to outcomes and to female
      breast cancer (FBC). METHODS AND MATERIALS: The Surveillance, Epidemiology, and
      End Results database was queried for all primary invasive MBC and FBC diagnosed
      from 1973 to 2008. Analyzable data included age, race, registry, grade, stage,
      estrogen and progesterone receptor status, type of surgery, and use of RT. Stage
      was defined as localized (LocD): confined to the breast; regional (RegD):
      involving skin, chest wall, and/or regional lymph nodes; and distant: M1. The
      primary endpoint was cause-specific survival (CSS). RESULTS: A total of 4276
      cases of MBC and 718,587 cases of FBC were identified. Male breast cancer
      constituted 0.6% of all breast cancer. Comparing MBC with FBC, mastectomy (M) was
      used in 87.4% versus 38.3%, and breast-conserving surgery in 12.6% versus 52.6%
      (P<10(-4)). For males with LocD, CSS was not significantly different for the 4.6%
      treated with lumpectomy/RT versus the 70% treated with M alone (hazard ratio [HR]
      1.33; 95% confidence interval [CI] 0.49-3.61; P=.57). Postmastectomy RT was
      delivered in 33% of males with RegD and was not associated with an improvement in
      CSS (HR 1.11; 95% CI 0.88-1.41; P=.37). There was a significant increase in the
      use of postmastectomy RT in MBC over time: 24.3%, 27.2%, and 36.8% for 1973-1987,
      1988-1997, and 1998-2008, respectively (P<.0001). Cause-specific survival for MBC
      has improved: the largest significant change was identified for men diagnosed in
      1998-2008 compared with 1973-1987 (HR 0.73; 95% CI 0.60-0.88; P=.0004).
      CONCLUSIONS: Surgical management of MBC is dramatically different than for FBC.
      The majority of males with LocD receive M despite equivalent CSS with
      lumpectomy/RT. Postmastectomy RT is greatly underutilized in MBC with RegD,
      although a CSS benefit was not demonstrated. Outcomes for MBC are improving,
      attributable to improved therapy and its use in this unscreened population.

PMID- 24138918
TI  - Chloroquine engages the immune system to eradicate irradiated breast tumors in
      mice.
AB  - PURPOSE: This study used chloroquine to direct radiation-induced tumor cell death
      pathways to harness the antitumor activity of the immune system. METHODS AND
      MATERIALS: Chloroquine given immediately after tumor irradiation increased the
      cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation
      induced autophagy and drove MCaK cells into a more rapid apoptotic and more
      immunogenic form of cell death. RESULTS: Chloroquine treatment made irradiated
      tumor vaccines superior at inducing strong interferon gamma-associated immune
      responses in vivo and protecting mice from further tumor challenge. In vitro,
      chloroquine slowed antigen uptake and degradation by dendritic cells, although T
      cell stimulation was unaffected. CONCLUSIONS: This study illustrates a novel
      approach to improve the efficacy of breast cancer radiation therapy by blocking
      endosomal pathways, which enhances radiation-induced cell death within the field
      and drives antitumor immunity to assist therapeutic cure. The study illuminates
      and merges seemingly disparate concepts regarding the importance of autophagy in
      cancer therapy.

PMID- 24138919
TI  - An anatomically validated brachial plexus contouring method for intensity
      modulated radiation therapy planning.
AB  - PURPOSE: To develop contouring guidelines for the brachial plexus (BP) using
      anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and
      computed tomography (CT) were used to obtain detailed visualizations of the BP
      region, with the goal of achieving maximal inclusion of the actual BP in a small
      contoured volume while also accommodating for anatomic variations. METHODS AND
      MATERIALS: CT and MRI were obtained for 8 cadavers positioned for intensity
      modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from
      MRI) and bone (from CT) were combined to create 8 separate enhanced CT project
      files. Dissection of the corresponding cadavers anatomically validated the
      reconstructions created. Seven enhanced CT project files were then automatically
      fitted, separately in different regions, to obtain a single dataset of
      superimposed BP regions that incorporated anatomic variations. From this dataset,
      improved BP contouring guidelines were developed. These guidelines were then
      applied to the 7 original CT project files and also to 1 additional file, left
      out from the superimposing procedure. The percentage of BP inclusion was compared
      with the published guidelines. RESULTS: The anatomic validation procedure showed
      a high level of conformity for the BP regions examined between the 3-dimensional
      reconstructions generated and the dissected counterparts. Accurate and detailed
      BP contouring guidelines were developed, which provided corresponding guidance
      for each level in a clinical dataset. An average margin of 4.7 mm around the
      anatomically validated BP contour is sufficient to accommodate for anatomic
      variations. Using the new guidelines, 100% inclusion of the BP was achieved,
      compared with a mean inclusion of 37.75% when published guidelines were applied.
      CONCLUSION: Improved guidelines for BP delineation were developed using combined
      MRI and CT imaging with validation by anatomic dissection.

PMID- 24138920
TI  - Multi-institutional quantitative evaluation and clinical validation of Smart
      Probabilistic Image Contouring Engine (SPICE) autosegmentation of target
      structures and normal tissues on computer tomography images in the head and neck,
      thorax, liver, and male pelvis areas.
AB  - PURPOSE: Clinical validation and quantitative evaluation of computed tomography
      (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine
      (SPICE). METHODS AND MATERIALS: CT images of 125 treated patients (32 head and
      neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions
      were autosegmented using SPICE and computational times were recorded. The number
      of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the
      liver, and 6 for the male pelvis regions. Using the clinical contours as
      reference, autocontours of 22 selected structures were quantitatively evaluated
      using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance
      (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the
      institution that treated the patients. RESULTS: The mean computational times to
      autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient.
      For the HN region, the mean DSC was >0.70 for all evaluated structures, and the
      MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for
      the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For
      the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged
      from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all
      structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured
      structures reviews by experts, 25 were scored useful as autocontoured or with
      minor edits for at least 90% of the patients and 33 were scored useful
      autocontoured or with minor edits for at least 80% of the patients. CONCLUSIONS:
      Compared with manual contouring, autosegmentation using SPICE for the HN, thorax,
      liver, and male pelvis regions is efficient and shows significant promise for
      clinical utility.

PMID- 24138921
TI  - Dosimetric comparison of 3-dimensional planning techniques using an intravaginal
      multichannel balloon applicator for high-dose-rate gynecologic brachytherapy.
AB  - PURPOSE: To study the dosimetric differences of various channel combinations of
      the Capri vaginal applicator. METHODS AND MATERIALS: The Capri consists of a
      single central channel (R1), an inner array of 6 channels (R2), and an outer
      array of 6 channels (R3). Three-dimensional plans were simulated for 6 channel
      arrangements (R1, R2, R12, R13, R23, and R123). Treatment plans were optimized to
      the applicator surface or 5-mm depth while minimizing dose to organs at risk
      (OARs: bladder, rectum, sigmoid, and urethra). The clinical target volume (CTV)
      was defined as a 5-mm circumferential shell extending 4 cm in length around the
      applicator. Clinical target volume coverage (Dmean, D90, V100, and V150) and OAR
      doses (D0.1 cm3, D1 cm3, D2 cm3, and Dmean) were compared. A comparison between
      the Capri (R123) and a conventional single-channel applicator was also done.
      Statistical significance (P value<.05) was evaluated with a 2-tailed t test.
      RESULTS: When prescribing to 5-mm depth, CTV coverage using all 13 channels
      (R123) versus a single channel (R1) was similar; however, when prescribing to the
      surface there were differences (P<.0001) in all CTV metrics except for the V150.
      The R1 plans had higher doses to all OARs compared with R123 plans (P<.007).
      Doses to OARs were not significantly different between R23 and R123 plans (P=.05
      .95), and CTV coverage differences were on the order of 1%. Capri R123 plans
      provided slightly lower CTV D90 and Dmean but equivalent OAR doses with smaller
      standard deviations compared with conventional cylinder plans for both
      prescriptions. CONCLUSIONS: The Capri multichannel applicator provides equivalent
      target coverage at 5-mm depth, with significantly reduced dose to OARs relative
      to using a single channel. Optimal plans can be achieved using R12 (lowest V150)
      or R123 or R23 (lowest OAR doses).

PMID- 24138922
TI  - Reduced dopamine response to amphetamine in subjects at ultra-high risk for
      addiction.
AB  - BACKGROUND: Not everyone who tries addictive drugs develops a substance use
      disorder. One of the best predictors of risk is a family history (FH) of
      substance use problems. In part, this might reflect perturbed mesolimbic dopamine
      responses. METHODS: We measured amphetamine-induced changes in [(11)C]raclopride
      binding in 1) high-risk young adults with a multigenerational FH of substance use
      disorders (n = 16); 2) stimulant drug-naive healthy control subjects with no
      known risk factors for addiction (n = 17); and 3) subjects matched to the high
      risk group on personal drug use but without a FH of substance use problems (n =
      15). RESULTS: Compared with either control group, the high-risk young adults with
      a multigenerational FH of substance use disorders exhibited smaller
      [(11)C]raclopride responses, particularly within the right ventral striatum. Past
      drug use predicted the dopamine response also, but including it as a covariate
      increased the group differences. CONCLUSIONS: Together, the results suggest that
      young people at familial high risk for substance use disorders have decreased
      dopamine responses to an amphetamine challenge, an effect that predates the onset
      of addiction.

PMID- 24138923
TI  - Glycogen synthase kinase-3 overexpression replicates electroretinogram anomalies
      of offspring at high genetic risk for schizophrenia and bipolar disorder.
AB  - BACKGROUND: Electroretinogram (ERG) anomalies occur in patients with psychiatric
      disorders and represent potential biomarkers for diagnosis. For instance,
      decreased rod ERG (b-wave amplitude at Vmax) is a biological endophenotype in
      young offspring at high genetic risk (HR) for schizophrenia (SZ) and bipolar
      disorder (BD). Also, a decrease in cone a-wave and rod a- and b- wave was
      observed in SZ patients. However, the biological underpinning of these anomalies
      remains unknown. Several genetic variants associated with enhanced risk for SZ
      and/or BD can activate glycogen synthase kinase-3 isozymes (GSK3alpha and beta).
      Here we examined the potential contribution of GSK3alpha and beta in the
      modulation of the ERG. METHODS: Cone and rod ERGs were recorded in mice having
      increased (prpGSK3beta mice) or reduced (GSK3beta(+/-) mice) GSK3beta expression
      and in GSK3alpha knockout (KO) mice. RESULTS: In prpGSK3beta mice, we observed a
      decrease in rod b-wave amplitude at Vmax, whereas enhanced b-wave amplitude at
      Vmax was found in GSK3beta(+/-) mice. An increase in cone a- and b-wave amplitude
      at Vmax and in rod b-wave amplitude at Vmax was observed in GSK3alpha-KO mice.
      CONCLUSIONS: GSK3 expression modulates some ERG parameters. The phenotype
      observed in prpGSK3beta mice is consistent with observations made in HRs. ERG
      anomalies observed in GSK3beta(+/-) and GSK3alpha-KO mice confirm an association
      between the rod and cone b-wave amplitude and the expression of GSK3 isozymes.
      Changes in GSK3 expression or activity may explain some ERG anomalies in HRs and
      patients, thus supporting the biological validity of ERG measurements as a
      valuable biomarker for psychiatric research.

PMID- 24138925
TI  - Preserved strategic grain-size regulation in memory reporting in patients with
      schizophrenia.
AB  - BACKGROUND: Cognitive and introspection disturbances are considered core features
      of schizophrenia. In real life, people are usually free to choose which aspects
      of an event they recall, how much detail to volunteer, and what degree of
      confidence to impart. Their decision will depend on various situational and
      personal goals. The authors explored whether schizophrenia patients are able to
      achieve a compromise between accuracy and informativeness when reporting semantic
      information. METHODS: Twenty-five patients and 23 healthy matched control
      subjects answered general knowledge questions requiring numerical answers (how
      high is the Eiffel tower?), freely at first and then through a metamemory-based
      control. In the second phase, they answered with respect to two predefined
      intervals, one narrow and one broad; attributed a confidence judgment to both
      answers; and afterward selected one of the two answers. Data were analyzed using
      analyses of variance with group as the between-subjects factor. RESULTS: Patients
      reported information at a self-paced level of precision less accurately than
      healthy participants. However, they benefited remarkably from the framing of the
      response and from the metamemory processes of monitoring and control to the point
      of improving their memory reporting and matching healthy subjects' accuracy.
      CONCLUSIONS: In spite of their memory deficit during free reporting, after
      accuracy monitoring, patients strategically regulated the grain size of their
      memory reporting and proved able to manage the competing goals of accuracy and
      informativeness. These results give some cause for optimism as to the possibility
      for patients to adapt to everyday life situations.

PMID- 24138926
TI  - The origin and the role of mitochondrial DNA in postinjury inflammation.

PMID- 24138924
TI  - Endocannabinoids promote cocaine-induced impulsivity and its rapid dopaminergic
      correlates.
AB  - BACKGROUND: Impaired decision making, a hallmark of addiction, is hypothesized to
      arise from maladaptive plasticity in the mesolimbic dopamine pathway. The
      endocannabinoid system modulates dopamine activity through activation of
      cannabinoid type 1 receptors (CB1Rs). Here, we investigated whether impulsive
      behavior observed following cocaine exposure requires CB1R activation. METHODS:
      We trained rats in a delay-discounting task. Following acquisition of stable
      performance, rats were exposed to cocaine (10 mg/kg, intraperitoneal) every other
      day for 14 days and locomotor activity was measured. Two days later, delay
      discounting performance was re-evaluated. To assess reversal of impulsivity,
      injections of a CB1R antagonist (1.5 mg/kg, intraperitoneal) or vehicle were
      given 30 minutes before the task. During the second experiment, aimed at
      preventing impulsivity rather than reversing it, CB1Rs were antagonized before
      each cocaine injection. In this experiment, subsecond dopamine release was
      measured in the nucleus accumbens during delay-discounting sessions before and
      after cocaine treatment. RESULTS: Blockade of CB1Rs reversed and prevented
      cocaine-induced impulsivity. Electrochemical results showed that during baseline
      and following disruption of endocannabinoid signaling, there was a robust
      increase in dopamine for immediate large rewards compared with immediate small
      rewards, but this effect reversed when the delay for the large reward was 10
      seconds. In contrast, dopamine release always increased for one-pellet options at
      minimal or moderate delays in vehicle-treated rats. CONCLUSIONS: Endocannabinoids
      play a critical role in changes associated with cocaine exposure. Cannabinoid
      type 1 receptor blockade may thus counteract maladaptive alterations in afferents
      to dopamine neurons, thereby preventing changes in dopaminergic activity
      underlying a loss of self-control.

PMID- 24138927
TI  - Integrative genomics identifies candidate microRNAs for pathogenesis of
      experimental biliary atresia.
AB  - BACKGROUND: Biliary atresia is a fibroinflammatory obstruction of extrahepatic
      bile duct that leads to end-stage liver disease in children. Despite advances in
      understanding the pathogenesis of biliary atresia, very little is known about the
      role of microRNAs (miRNAs) in onset and progression of the disease. In this
      study, we aimed to investigate the entire biliary transcriptome to identify
      miRNAs with potential role in the pathogenesis of bile duct obstruction. RESULTS:
      By profiling the expression levels of miRNA in extrahepatic bile ducts and
      gallbladder (EHBDs) from a murine model of biliary atresia, we identified 14
      miRNAs whose expression was suppressed at the times of duct obstruction and
      atresia (>=2 fold suppression, P < 0.05, FDR 5%). Next, we obtained 2,216
      putative target genes of the 14 miRNAs using in silico target prediction
      algorithms. By integrating this result with a genome-wide gene expression
      analysis of the same tissue (>=2 fold increase, P < 0.05, FDR 5%), we identified
      26 potential target genes with coordinate expression by the 14 miRNAs. Functional
      analysis of these target genes revealed a significant relevance of miR-30b/c, 
      133a/b, -195, -200a, -320 and -365 based on increases in expression of at least 3
      target genes in the same tissue and 1st-to-3rd tier links with genes and gene
      groups regulating organogenesis and immune response. These miRNAs showed higher
      expression in EHBDs above livers, a unique expression in cholangiocytes and the
      subepithelial compartment, and were downregulated in a cholangiocyte cell line
      after RRV infection. CONCLUSIONS: Integrative genomics reveals functional
      relevance of miR-30b/c, -133a/b, -195, -200a, -320 and -365. The coordinate
      expression of miRNAs and target genes in a temporal-spatial fashion suggests a
      regulatory role of these miRNAs in pathogenesis of experimental biliary atresia.

PMID- 24138929
TI  - Longitudinal levels and bouts of sedentary time among adolescent girls.
AB  - BACKGROUND: Adolescent girls are one of the most sedentary demographic groups. A
      better understanding of their accumulation of sedentary time is needed to inform
      future interventions. The purpose of this study was to examine the longitudinal
      levels and bouts of objectively measured sedentary time accumulated during
      different days of the week and periods of the weekday among a large sample of
      adolescent girls. METHODS: The results are based on 655 adolescent girls from the
      Girls in Sport Intervention and Research Project. Levels and bouts of sedentary
      time were derived from accelerometer data collected at baseline and 18-month
      follow-up. Total, weekday, weekend, school (i.e., morning bell to afternoon
      bell), after school (i.e., afternoon bell to 19:00), and evening (i.e. 19:01 to
      23:59) sedentary time levels and bouts were calculated. Repeated-measures ANCOVAs
      were conducted to examine differences in sedentary time levels and bouts between
      days and time periods after adjusting for wear time, accelerometer model, and
      intervention group. RESULTS: Cross-sectional analyses revealed that levels and
      bouts of sedentary time were higher on weekdays compared to weekend days at
      baseline. Similar trends were observed at follow-up. In addition, percentage of
      wear time spent sedentary and bouts/hr of sedentary time were highest in the
      evening compared to the school and after school periods at both baseline and
      follow-up. Longitudinal analyses revealed that levels and bouts of sedentary time
      were higher at follow-up compared to baseline across the different days of the
      week and periods of the weekday examined, with the biggest increase (15%)
      occurring in the school period. CONCLUSIONS: Future interventions targeting
      sedentary time among adolescent girls should consider developing strategies to
      reduce and break up prolonged sedentary time during the school day and in the
      evening.

PMID- 24138928
TI  - DNA methylation age of human tissues and cell types.
AB  - BACKGROUND: It is not yet known whether DNA methylation levels can be used to
      accurately predict age across a broad spectrum of human tissues and cell types,
      nor whether the resulting age prediction is a biologically meaningful measure.
      RESULTS: I developed a multi-tissue predictor of age that allows one to estimate
      the DNA methylation age of most tissues and cell types. The predictor, which is
      freely available, was developed using 8,000 samples from 82 Illumina DNA
      methylation array datasets, encompassing 51 healthy tissues and cell types. I
      found that DNA methylation age has the following properties: first, it is close
      to zero for embryonic and induced pluripotent stem cells; second, it correlates
      with cell passage number; third, it gives rise to a highly heritable measure of
      age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis
      of 6,000 cancer samples from 32 datasets showed that all of the considered 20
      cancer types exhibit significant age acceleration, with an average of 36 years.
      Low age-acceleration of cancer tissue is associated with a high number of somatic
      mutations and TP53 mutations, while mutations in steroid receptors greatly
      accelerate DNA methylation age in breast cancer. Finally, I characterize the 353
      CpG sites that together form an aging clock in terms of chromatin states and
      tissue variance. CONCLUSIONS: I propose that DNA methylation age measures the
      cumulative effect of an epigenetic maintenance system. This novel epigenetic
      clock can be used to address a host of questions in developmental biology, cancer
      and aging research.

PMID- 24138930
TI  - When expressions make impressions-nurses' narratives about meeting severely ill
      patients in home nursing care: a phenomenological-hermeneutic approach to
      understanding.
AB  - Registered nurses (RNs) working in homecare encounter severely ill and palliative
      patients whose expressions may cause ethical challenges and influence their daily
      work. The aim of this qualitative study was to illuminate and interpret the
      meaning of nurses' lived experiences when meeting these patients. Narrative
      interviews were conducted with 10 RNs working in home nursing care. These
      interviews were audiotaped and transcribed verbatim to a text and interpreted by
      a phenomenological-hermeneutic method inspired by Ricoeur. The meaning of the
      RNs' lived experience of patients' expressions was formulated into four themes.
      The first theme, Being open for the presence of the Other, includes two
      subthemes: "Sensing vulnerability" and "Empathizing with." The second theme,
      Being satisfied, entails the subthemes, "Feeling exceptional" and "Being
      trusted." The third theme, Being frustrated, contains the subthemes, "Being
      disappointed" and "Being angry." The fourth and final theme, Being ambivalent,
      includes one subtheme: "Being generous or reserved." Patients' expressions that
      make impressions on nurses create emotional waves. Expressions leave impressions
      that call upon the nurse, and confront her with taking the risk of letting
      intuition and pre-reflexive feelings gain entry to her care. Allowing for the
      Other's presence is seen as a precondition, which means facing humanity and
      sensing a vulnerability in herself as well as in the Other. Understanding and
      balancing this emotional dimension in care seems to cause confusion and distress
      within the nurses. Realizing how their feelings may lead to either generosity or
      aloofness towards the patient is upsetting. Our interpretation suggests that
      these impressions echo confusion according to the role of being a professional
      nurse. There is a need to pay more attention to how the emotional dimension in
      care is understood and impacts the way nurses perform their professional role. 

PMID- 24138932
TI  - Moroccan parents caring for children with juvenile idiopathic arthritis: positive
      and negative aspects of their experiences.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) can lead to serious disability in
      children and adolescents, requiring intensive home care usually provided by
      parents .These parents must also cope with physical, familial, social and
      financial constraints.The aim of this study is to evaluate the positive and
      negative impacts of caregiving on parents to children with JIA, and identify
      diseases-related variables that affect these outcomes. METHODS: Cross-sectional
      study including 47 patients diagnosed with JIA defined by the International
      League of association for Rheumatology (ILAR) 2001 classification. Socio
      demographic, clinical and biological data related to patient and disease were
      collected. Positive and negative effects of caregiving on parents of children
      with JIA were assessed via a validated instrument; the Caregiver Reaction
      Assessment (CRA).The CRA assesses parent's self-esteem, financial problems,
      health problems, disrupted schedule and lack of family support. All parents
      completed the CRA questionnaire. A statistical analysis was conducted to
      determine the influence of disease-related variables on caregivers. RESULTS:
      Forty-seven patients were included with 40.4% female. The average patient age was
      11 years, and a mean patient body mass index (BMI) was 18. Forty patients were in
      school. Median disease duration of JIA was 4 years. The most frequent arthritis
      subtype was persistent oligoarthritis in 12-patients. Nearly 15% had extra
      articular manifestations most frequently ocular involvement (6.4%). Median of
      global Visual analogic scale (VAS) was 20 and median Child health assessment
      questionnaire (CHAQ) was 0. The primary caregiver was the mother for all
      patients. Mean maternal age was 38 years, 42% of mothers were illiterate, and
      nearly all (95%) were without employment. The mean values of different dimensions
      of the CRA were respectively: self-esteem 3.5, financial problems 3.7, health
      problem 2.4, disrupted schedule 3.6 and familial support 2.9. Disrupted schedule
      of parents was correlated with disease severity assessed by physician VAS (p =
      0.02). Financial problems of parents were significantly associated with disease
      duration (p = 0.04). There was no significant association between the type of
      JIA, activity or severity of the disease and other dimensions of the CRA.
      CONCLUSION: This study suggests that the management of children with JIA has a
      high negative impact among caregiving parents, represented mainly by the
      disruption of their activities, the lack of family support, financial problems
      and health problems. However, caregiving often also improves caregiver's self
      esteem (feeling of gratification to be helping).

PMID- 24138931
TI  - MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with
      survival in nasopharyngeal carcinoma.
AB  - BACKGROUND: MiRNAs play important roles in diverse biological processes including
      tumorigenesis. However, little is known about the function and mechanism of miR
      451 in nasopharyngeal carcinoma (NPC). METHODS: Quantitative RT-PCR was used to
      quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier
      curves were used to estimate the association between miR-451 expression and
      survival. The MTT, colony formation, Transwell migration and invasion assays, and
      a xenograft model were performed. A miR-451 target was confirmed using luciferase
      reporter assays, quantitative RT-PCR, and Western blotting. RESULTS: MiR-451 was
      significantly downregulated in NPC cell lines and clinical tissues (P < 0.01).
      Patients with low expression of miR-451 had poorer overall survival (HR, 1.98;
      95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07
      2.62; P = 0.02) than patients with high expression. MiR-451 was an independent
      prognostic factor in NPC in multivariate Cox regression analysis. Ectopic
      expression of miR-451 suppressed cell viability, colony formation, and cell
      migration and invasion in vitro, and inhibited xenograft tumor growth in vivo.
      MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth
      and invasion. CONCLUSIONS: The newly identified miR-451/MIF pathway provides
      insight into NPC initiation and progression, and may represent a novel
      therapeutic target.

PMID- 24138933
TI  - The Drosophila phenotype ontology.
AB  - BACKGROUND: Phenotype ontologies are queryable classifications of phenotypes.
      They provide a widely-used means for annotating phenotypes in a form that is
      human-readable, programatically accessible and that can be used to group
      annotations in biologically meaningful ways. Accurate manual annotation requires
      clear textual definitions for terms. Accurate grouping and fruitful programatic
      usage require high-quality formal definitions that can be used to automate
      classification. The Drosophila phenotype ontology (DPO) has been used to annotate
      over 159,000 phenotypes in FlyBase to date, but until recently lacked textual or
      formal definitions. RESULTS: We have composed textual definitions for all DPO
      terms and formal definitions for 77% of them. Formal definitions reference terms
      from a range of widely-used ontologies including the Phenotype and Trait Ontology
      (PATO), the Gene Ontology (GO) and the Cell Ontology (CL). We also describe a
      generally applicable system, devised for the DPO, for recording and reasoning
      about the timing of death in populations. As a result of the new formalisations,
      85% of classifications in the DPO are now inferred rather than asserted, with
      much of this classification leveraging the structure of the GO. This work has
      significantly improved the accuracy and completeness of classification and made
      further development of the DPO more sustainable. CONCLUSIONS: The DPO provides a
      set of well-defined terms for annotating Drosophila phenotypes and for grouping
      and querying the resulting annotation sets in biologically meaningful ways. Such
      queries have already resulted in successful function predictions from phenotype
      annotation. Moreover, such formalisations make extended queries possible,
      including cross-species queries via the external ontologies used in formal
      definitions. The DPO is openly available under an open source license in both OBO
      and OWL formats. There is good potential for it to be used more broadly by the
      Drosophila community, which may ultimately result in its extension to cover a
      broader range of phenotypes.

PMID- 24138935
TI  - Sagittal plane ground reaction forces, centre of pressure and centre of mass in
      trotting horses.
AB  - The aims of this study were to measure ground reaction forces (GRFs) of
      concurrently loaded limbs and to evaluate spatial relationships between the
      centre of pressure (COP) and centre of mass (COM) in trotting horses. Kinematic
      (120Hz) and GRF data were collected at trot from three trials of eight horses
      using four force plates (960 Hz). Forelimb and hind limb GRFs were measured, COP
      was calculated from the resultant vertical GRF vector and COM was calculated by
      summation of weighted segmental COMs. Peak total vertical force (19.3 +/- 1.3N/kg
      at 45.1 +/- 2.3% diagonal stance) coincided with zero total longitudinal force
      (45.1 +/- 2.4% stance). Initially, COP position corresponded with the fore or
      hind hoof of the diagonal that contacted the ground earlier. During diagonal
      overlap, COP position reflected forelimb contribution to total vertical GRF; it
      maintained a fairly constant position relative to the base of support through the
      middle part of stance, then moved cranially in the last third of stance towards
      the fore hoof, which was always the last hoof to leave the ground. The COM moved
      forward continuously; its longitudinal velocity decreased with the net braking
      force in early stance and increased with the net propulsive force in late stance.
      The COM was caudal to the COP in early stance, coincident at 35.8 +/- 4.4% stance
      and was maximally ahead of the COP at 67.6 +/- 4.8% stance. Changes in the
      spatial relationship between COP and COM affect the moment arms of the forelimb
      and hind limb vertical GRFs and their effect in generating a pitching torque
      around the COM.

PMID- 24138934
TI  - Scn8a voltage-gated sodium channel mutation alters seizure and anxiety responses
      to acute stress.
AB  - Stress is known to trigger seizures in patients with epilepsy, highlighting the
      physiological stress response as a possible therapeutic target for epilepsy
      treatment. Nevertheless, little is currently known about how a genetic
      predisposition to epilepsy interacts with the stress response to influence
      seizure outcome. To address this question, we examined the effect of acute stress
      on seizure outcome in mice with mutations in the voltage-gated sodium channel
      (VGSC) gene Scn8a. Scn8a mutants display spontaneous spike-wave discharges (SWDs)
      characteristic of absence epilepsy. We saw that the baseline frequency of SWDs in
      Scn8a mutants correlates closely with the diurnal activity of the hypothalamic
      pituitary-adrenal (HPA) axis, with a peak in seizure activity occurring at around
      the same time as the peak in corticosterone (1700-1900h). A 20-min acute
      restraint stress administered in the morning increases the frequency of
      spontaneous SWDs immediately following the stressor. Seizure frequency then
      returns to baseline levels within 3h after stressor exposure, but the subsequent
      evening peak in seizure frequency is delayed and broadened, changes that persist
      into the next evening and are accompanied by long-lasting changes in HPA axis
      activity. Scn8a mutants also show increased anxiety-like behavior in mildly
      stressful situations. A 20-min acute restraint stress can also increase the
      severity and duration of chemically induced seizures in Scn8a mutants, changes
      that differ from wild-type littermates. Overall, our data show that a voltage
      gated sodium channel mutation can alter the behavioral response to stress and can
      interact with the stress response to alter seizure outcome. 

PMID- 24138936
TI  - Molecular characterization of Cryptosporidium spp. from foals in Italy.
AB  - Fourteen Cryptosporidium isolates from hospitalized foals were genotyped and
      subtyped using PCR-RFLP analysis of the 18S rDNA. Cryptosporidium parvum and
      Cryptosporidium horse genotype were detected in 3 and 11 stool specimens,
      respectively. Sequences of the gp60 gene of Cryptosporidium horse genotype
      allowed identification of the subtype family VIaA15G4, defining a novel
      microsatellite pattern within horse subtype VIa. Cryptosporidium horse genotype
      has only been described occasionally worldwide and this is the first time it has
      been identified in foals from Italy. 

PMID- 24138937
TI  - Systematic development of a text-driven and a video-driven web-based computer
      tailored obesity prevention intervention.
AB  - BACKGROUND: This paper describes the systematic development of a text-driven and
      a video-driven web-based computer-tailored intervention aimed to prevent obesity
      among normal weight and overweight adults. We hypothesize that the video-driven
      intervention will be more effective and appealing for individuals with a low
      level of education. METHODS AND DESIGN: The Intervention Mapping protocol was
      used to develop the interventions, which have exactly the same educational
      content but differ in the format in which the information is delivered. One
      intervention is fully text-based, while in the other intervention in addition to
      text-based feedback, the core messages are provided by means of videos. The aim
      of the interventions is to prevent weight gain or achieve modest weight loss by
      making small changes in dietary intake or physical activity. The content of the
      interventions is based on the I-Change Model and self-regulation theories and
      includes behavior change methods such as consciousness raising, tailored feedback
      on behavior and cognitions, goal setting, action and coping planning, and
      evaluation of goal pursuit. The interventions consist of six sessions. In the
      first two sessions, participants will set weight and behavioral change goals and
      form plans for specific actions to achieve the desired goals. In the remaining
      four sessions, participants' will evaluate their progress toward achievement of
      the behavioral and weight goals. They will also receive personalized feedback on
      how to deal with difficulties they may encounter, including the opportunity to
      make coping plans and the possibility to learn from experiences of others. The
      efficacy and appreciation of the interventions will be examined by means of a
      three-group randomized controlled trial using a waiting list control group.
      Measurements will take place at baseline and six and twelve months after
      baseline. Primary outcome measures are body mass index, physical activity, and
      dietary intake. DISCUSSION: The present paper provides insight into how web-based
      computer-tailored obesity prevention interventions consisting of self-regulation
      concepts and text-driven and video-driven messages can be developed
      systematically. The evaluation of the interventions will provide insight into
      their efficacy and will result in recommendations for future web-based computer
      tailored interventions and the additional value of using video tailoring. TRIAL
      REGISTRATION: NTR3501.

PMID- 24138938
TI  - Applying a palliative care approach in residential care: effects on nurse
      assistants' work situation.
AB  - OBJECTIVES: The aim was to investigate the effects of an intervention that
      applies a palliative care approach in residential care upon nurse assistants'
      level of strain, job satisfaction, and view of leadership. METHOD: A quasi
      experimental, pretest and posttest design was used. Study circles with workshops
      involving nurse assistants (n = 75) and their superiors (n = 9) focusing on
      emotional and existential issues in palliative care were evaluated using a
      questionnaire answered by the nurse assistants at baseline (November 2009), post
      intervention (May 2010), and six-month follow-up (November 2010) in comparison
      with controls (n = 110). RESULTS: Directly after the intervention, the job
      satisfaction of the nurse assistants decreased and they perceived the leadership
      more negatively than before the intervention. Six months later, strain as a
      result of criticism from residents and their superiors and having difficulty in
      balancing emotional involvement had decreased. SIGNIFICANCE OF RESULTS: The
      intervention initially seemed to decrease the well-being of the nurse assistants,
      which could be the result of their increased awareness of the residents' and
      relatives' needs, in combination with limited support. More emphasis should be
      placed on the role of leadership when implementing changes in practice.

PMID- 24138939
TI  - Enhancement of kinase selectivity in a potent class of arylamide FMS inhibitors.
AB  - Structure-activity relationship (SAR) studies on a highly potent series of
      arylamide FMS inhibitors were carried out with the aim of improving FMS kinase
      selectivity, particularly over KIT. Potent compound 17r (FMS IC50 0.7 nM, FMS
      cell IC50 6.1 nM) was discovered that had good PK properties and a greater than
      fivefold improvement in selectivity for FMS over KIT kinase in a cellular assay
      relative to the previously reported clinical candidate 4. This improved
      selectivity was manifested in vivo by no observed decrease in circulating
      reticulocytes, a measure of bone safety, at the highest studied dose. Compound
      17r was highly active in a mouse pharmacodynamic model and demonstrated disease
      modifying effects in a dose-dependent manner in a strep cell wall-induced
      arthritis model of rheumatoid arthritis in rats.

PMID- 24138940
TI  - Structure-based design and synthesis of potent benzothiazole inhibitors of
      interleukin-2 inducible T cell kinase (ITK).
AB  - Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell
      receptor signalling cascade, may represent a novel treatment for allergic asthma.
      Here we report the structure-based optimization of a series of benzothiazole
      amides that demonstrate sub-nanomolar inhibitory potency against ITK with good
      cellular activity and kinase selectivity. We also elucidate the binding mode of
      these inhibitors by solving the X-ray crystal structures of several inhibitor-ITK
      complexes. 

PMID- 24138941
TI  - Synthesis of novel ciprofloxacin analogues and evaluation of their anti
      proliferative effect on human cancer cell lines.
AB  - A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted
      piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been
      synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and evaluated for their
      inhibitory activity on the proliferation of human caucasian acute lymphoblastic
      leukemia cells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human
      colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin
      analogues 3t at 50 MUM showed comparable potency to doxorubicin (10 MUM) in all
      three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35%
      selectively over other two cell lines.

PMID- 24138942
TI  - Orexin and neuropeptide Y: tissue specific expression and immunoreactivity in the
      hypothalamus and preoptic area of the cichlid fish Cichlasoma dimerus.
AB  - Neuropeptide Y (NPY) and orexin are neuropeptides involved in the regulation of
      feeding in vertebrates. In this study we determined the NPY and orexin mRNA
      tissue expression and their immunoreactivity distribution in both preoptic area
      and hypothalamus, regions involved in the regulation of feeding behavior. Both
      peptides presented a wide expression in all tissues examined. The NPY
      immunoreactive (ir) cells were localized in the ventral nucleus posterioris
      periventricularis (NPPv) and numerous ir-NPY fibers were found in the nucleus
      lateralis tuberis (NLT), the nucleus recess lateralis (NRL) and the
      neurohypophysis. Ir-orexin cells were observed in the NPPv, dorsal NLT, ventral
      NLT, lateral NLT (NLTl) and the lateral NRL. Ir-orexin fibers were widespread
      distributed along all the hypothalamus, especially in the NLTl. Additionally, we
      observed the presence of ir-orexin immunostaining in adenohypophyseal cells,
      especially in somatotroph cells and the presence of a few ir-orexin-A fibers in
      the neurohypophysis. In conclusion, both peptides have an ubiquitous mRNA tissue
      expression and are similarly distributed in the hypothalamus and preoptic area of
      Cichlasoma dimerus. The presence of ir-orexin in adenohypohyseal cells and the
      presence of ir-orexin and NPY fibers in the neurohypophysis suggest that both
      peptides may play an important neuroendocrine role in anterior pituitary. 

PMID- 24138943
TI  - Marce International Society position statement on psychosocial assessment and
      depression screening in perinatal women.
AB  - The position statement aims to articulate the arguments for and against universal
      psychosocial assessment and depression screening, and provide guidance to assist
      decision-making by clinicians, policy makers and health services. More
      specifically it: 1. Outlines the general principles and concepts involved in
      psychosocial assessment and depression screening; 2. Outlines the current debate
      regarding benefits and risks in this area of practice including the clinical
      benefits and the ethical, cultural and resource implications of undertaking
      universal psychosocial assessment in the primary health care setting; 3. Provides
      a document that will assist with advocacy for the development of perinatal mental
      health services in the primary care setting. The statement does not set out to
      make specific recommendations about psychosocial assessment and depression
      screening (as these will need to be devised locally depending on existing
      resources and models of care) nor does it attempt to summarise the vast evidence
      base relevant to this debate. 

PMID- 24138944
TI  - A phase I study of decitabine and rapamycin in relapsed/refractory AML.
AB  - A phase I study utilizing decitabine (DAC) followed by the mammalian target of
      rapamycin (mTOR) inhibitor, rapamycin, in patients with relapsed/refractory adult
      AML was undertaken to assess safety and feasibility. Patients received DAC
      20mg/m(2) intravenously daily for 5 days followed by rapamycin from day 6 to day
      25 at doses of 2 mg, 4 mg, and 6 mg/day in a standard 3+3 dose escalation design.
      Twelve patients completed treatment for safety evaluation. Maximum tolerated dose
      (MTD) was not reached, and except for grade 3 mucositis in 4 patients, no other
      significant unexpected non-hematologic toxicities have occurred indicating safety
      of this regimen. This trial is registered at clinical trials.gov as NCT00861874.

PMID- 24138945
TI  - Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia.
AB  - Dysregulation of microRNA let-7a-3 has been identified in several solid tumors
      and is associated with prognosis of patients. However, the pattern of let-7a-3
      expression and the impact on prognosis has not yet been studied in acute myeloid
      leukemia (AML). The purpose of this study is to investigate the expression status
      of let-7a-3 and its clinical significance in AML patients using real-time
      quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de
      novo AML. There was no significant difference in age, blood parameters, FAB/WHO
      subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT,
      IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3
      overexpression (P>0.05). The patients with let-7a-3 overexpression had similar
      rates of complete remission (CR) as those without let-7a-3 overexpression (50%
      vs. 56%, P=0.693). Although the overall survival (OS) of AML patients with let-7a
      3 overexpression (median 12 months,) was shorter than those without
      overexpression (median 25 months), the difference was not statistically
      significant (P=0.228). However, among those 51 obtained CR, patients with let-7a
      3 overexpression had significantly shorter OS than those without let-7a-3
      overexpression (P=0.029). The difference in relapse-free survival (RFS) was also
      significant between two groups (P=0.005). These findings suggest that let-7a-3
      overexpression is a common event and is associated with poor clinical outcome in
      AML. 

PMID- 24138946
TI  - An unusual instance of stridor: airway obstruction from a nasogastric tube knot
      in a 1-month old infant.
AB  - We report a 1 month old infant with a spontaneously knotted nasogastric tube.
      Attempted removal of the nasogastric tube was unsuccessful, prompting further
      investigation. Plain radiographs revealed a large, multi-looped knot impacted in
      the nasopharynx and oropharynx. The tube was subsequently removed through the
      mouth under general anesthesia without complication, revealing a large,
      impressive knot of the distal end of the nasogastric tube.

PMID- 24138947
TI  - Lambert-Eaton syndrome, an unrecognized treatable pediatric neuromuscular
      disorder: three patients and literature review.
AB  - BACKGROUND: Lambert-Eaton myasthenic syndrome, a presynaptic neuromuscular
      junction autoimmune disorder, rarely occurs in children. Patients typically
      present with proximal lower extremity weakness with areflexia. METHODS: We report
      three children presenting between ages 9 and 10 years diagnosed with Lambert
      Eaton myasthenic syndrome 2 years, 1 year, and 5 months later, respectively.
      Their clinical attributes are correlated with nine other pediatric Lambert-Eaton
      myasthenic syndrome patients found in our literature review. RESULTS: These
      patients were identified as having Lambert-Eaton myasthenic syndrome during their
      evaluation for proximal weakness. Low-amplitude compound muscle action potentials
      classically facilitating >100% with voluntary exercise and/or 50 Hz stimulation
      were essential to diagnosis. Three of the 12 children had associated
      malignancies, two of them had lymphoproliferative disorders with onset of
      symptoms more rapid than the rest, and the third had neuroblastoma. The nine
      nonparaneoplastic Lambert-Eaton myasthenic syndrome patients responded to
      immunomodulatory therapy with close return to their baseline function. Complete
      remission no longer necessitating medication was reported in two patients. Follow
      up up to 17 years was available on two patients previously reported. CONCLUSION:
      Lambert-Eaton myasthenic syndrome is a diagnosis that must be considered in
      children presenting with unidentified proximal muscle weakness. In most children,
      Lambert-Eaton myasthenic syndrome is a primary autoimmune disorder that is
      treatable. Nevertheless, a search for malignancy is recommended.

PMID- 24138948
TI  - Corticosteroid therapy for duchenne muscular dystrophy: improvement of
      psychomotor function.
AB  - BACKGROUND: Of the numerous clinical trials for Duchenne muscular dystrophy, only
      the corticosteroid prednisolone has shown potential for temporal improvement in
      motor ability. In this study, the effects of prednisolone on intellectual ability
      are examined in 29 cases of Duchenne muscular dystrophy because little
      information has been reported. And also, motor functions and cardiac functions
      were evaluated. METHODS: The treated group was administered prednisolone (0.75
      mg/kg) orally on alternate days and the compared with the untreated control
      group. Gene mutations were investigated. The patients were examined for
      intelligence quotient adequate for age, brain natriuretic peptide, creatine
      kinase, and manual muscle testing before treatment and after the period 6 months
      to 2 years. RESULTS: Intelligence quotient scores of the treated increased to 6.5
      +/- 11.9 (mean +/- standard deviation) were compared with the controls 2.1 +/-
      4.9 (P = 0.009). Intelligence quotient scores of the patients with nonsense point
      mutations improved significantly (21.0 +/- 7.9) more than those with deletion or
      duplication (1.9 +/- 9.0; P = 0.015). Motor function, such as time to stand up,
      of those treated improved significantly and brain natriuretic peptide level was
      reduced to a normal level after treatment in 15 patients (73%). CONCLUSIONS: Our
      results demonstrate the effectiveness of prednisolone in improving intellectual
      impairment as well as in preserving motor function and brain natriuretic peptide
      levels. We presume that prednisolone has a read-through effect on the stop codons
      in the central nervous systems of Duchenne muscular dystrophy because
      intelligence quotient of point mutation case was improved significantly.

PMID- 24138949
TI  - New autopsy findings in different brain regions of a preterm neonate with
      kernicterus: neurovascular alterations and up-regulation of efflux transporters.
AB  - BACKGROUND: Kernicterus is an irreversible brain damage caused by bilirubin
      deposition in selective brain regions. Sick and preterm infants with
      hyperbilirubinemia are particularly susceptible to the condition. METHODS: We
      studied autopsied brain tissue from a premature female infant with kernicterus
      with a bilirubin:albumin molar ratio of 1.0, hypoxia, acidosis, and seizures. The
      patient, previously described as having cerebellar axon/myelin loss and
      angiogenic sprouting, was assessed for histopathological features in brain
      regions less investigated, such as hippocampus and corpus striatum. Results were
      compared with age-matched controls. RESULTS: Increased blood vessel density with
      poorly defined lumen structures was observed in the mesencephalon, pons, and
      medulla oblongata, and, more predominantly, in the corpus striatum and
      hippocampus. These two regions exhibited increased expression of vascular
      endothelial growth factor, paralleled by vascular endothelial growth factor
      receptor-2, and albumin extravasation into the brain parenchyma. No similar
      findings were observed in the nonjaundiced babies with hypoxia that served as
      controls (one preterm with sepsis and a term infant with pneumonia). We found
      increased cellular expression of multidrug resistance-associated protein 1 and P
      glycoprotein in the hippocampus, known as defensive mechanisms against bilirubin
      induced cytotoxicity. Increased density of blood vessels and microvascular
      permeability, together with parenchymal albumin, may have contributed to
      increasing the brain content and retention of bilirubin, a condition implicated
      in kernicterus disease. CONCLUSIONS: This novel finding in a premature baby with
      kernicterus and associated risk factors deserves to be investigated in similar
      patients to better understand the less-well described effects of bilirubin
      induced neurological sequelae in preterm infants.

PMID- 24138950
TI  - Cerebrospinal fluid TNF-alpha, IL-6, and IL-8 in children with bacterial
      meningitis.
AB  - OBJECTIVE: We evaluated the levels of cerebrospinal fluid concentrations of tumor
      necrosis factor-alpha, interleukin-6, and interleukin-8 in bacterial meningitis
      in children. METHODS: The study included children up to 14 years of age admitted
      to a pediatric ward with fever, headache, vomiting, and seizures. The diagnosis
      of bacterial meningitis was based on clinical features: physical examination,
      blood and cerebrospinal fluid cytochemical findings, Gram stain, and bacterial
      culture. The cerebrospinal fluid levels of tumor necrosis factor-alpha,
      interleukin-6, and interleukin-8 were measured in 57 children with bacterial
      meningitis, 15 with viral meningitis, and 15 controls by enzyme-linked
      immunosorbent assay methods. RESULTS: The mean concentrations of cerebrospinal
      fluid, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were 1108 +/
      183, 652 +/- 287, and 442 +/- 120 pg/mL, respectively, in children with
      bacterial meningitis and were significantly increased in those in the viral
      meningitis group (tumor necrosis factor-alpha : 711 +/- 105, IL-6 : 272 +/- 161,
      IL-8 : 175 +/- 62 pg/mL; P < 0.001) or control (390 +/- 37, 59 +/- 17, 19 +/- 13
      pg/mL, respectively, P < 0.001). At optimum cutoff level based on the receiver
      operating characteristic curve, cerebrospinal fluid cytokines (tumor necrosis
      factor-alpha, interleukin-6, and interleukin-8) showed sensitivity and
      specificity of 100% for the diagnosis of bacterial meningitis. For
      differentiation of bacterial from viral meningitis, cerebrospinal fluid level of
      tumor necrosis factor-alpha, IL-6, and IL-8 showed sensitivity and specificity of
      94.7% and 86.7%, 80.7% and 53.3%, and 89.5% and 86.7%, respectively. CONCLUSION:
      The increased concentration of cerebrospinal fluid tumor necrosis factor-alpha,
      interleukin-6, and interleukin-8 in children with meningitis suggests a role in
      the pathogenesis of bacterial meningitis and these levels might prove to be
      useful in children whose diagnosis is in question.

PMID- 24138951
TI  - Risk factors and scoring system as a prognostic tool for epilepsy after neonatal
      seizures.
AB  - BACKGROUND: Neonatal seizures may cause irreversible changes to the immature
      brain and. A scoring system for early prognostic information could be a useful
      clinical tool. The aim of the study was to analyze risk factors for epilepsy
      after neonatal seizures, to validate Garfinkle's scoring system, and to analyze
      whether a new scoring system is feasible. METHODS: A retrospective study of 176
      newborns (59.1% boys, 40.9% girls, 70.5% term, 29.5% preterm; mean birth weight
      2820 g), admitted to the Department of Neonatology, Division of Pediatrics,
      University Medical Centre, Ljubljana, because of neonatal seizures (clinical
      and/or neurophysiological), was performed. Epilepsy rate between 2 and 12 years
      of follow-up was 18.1%. Five independent predictors from Garfinkle's study and
      other known predictors were entered into hierarchical binary logistic regression
      models and analyzed through four steps to identify independent predictors of
      epilepsy. We tested whether any of the predictors was an effect modifier.
      RESULTS: Of five potential predictors from Garfinkle's score,
      electroencephalograph background findings and etiology were predictive.
      Etiologies, gestation, mode of delivery, duration of seizures, and other risk
      factors at birth were found to be independent predictors. Duration of seizures
      has a different effect on prognosis depending on the gestational age. CONCLUSION:
      Gestational age determines the association between duration of seizures and
      epilepsy. Scoring systems to predict development of epilepsy after neonatal
      seizures need to limit interaction between important predictor variables.

PMID- 24138952
TI  - Automatically quantified diffuse excessive high signal intensity on MRI predicts
      cognitive development in preterm infants.
AB  - BACKGROUND: Cognitive and language impairments constitute the majority of
      disabilities observed in preterm infants. It remains unclear if diffuse excessive
      high signal intensity on magnetic resonance imaging at term represents delayed
      white matter maturation or pathology. METHODS: We hypothesized that diffusion
      tensor imaging-based objectively quantified diffuse excessive high signal
      intensity measures at term will be strong predictors of cognitive and language
      development at 2 years in a cohort of 41 extremely low birth weight (<=1000 g)
      infants. Using an automated probabilistic atlas, mean diffusivity maps were used
      to objectively segment and quantify diffuse excessive high signal intensity
      volume and mean, axial, and radial diffusivity measures. Standardized
      neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant
      Development, third edition. RESULTS: Thirty-six of the 41 infants (88%) had
      complete developmental data at follow-up. Objectively quantified diffuse
      excessive high signal intensity volume correlated significantly with cognitive
      and language scores at 2 years (P < 0.001 for both). The sum values of the three
      diffusivity measures in detected diffuse excessive high signal intensity regions
      also correlated significantly with the Bayley scores (r(2) 34.7%; P < 0.001 for
      each). Infants in the highest quartile for diffuse excessive high signal
      intensity volumes had scores between 19 and 24 points lower than infants in the
      lowest quartile (P < 0.01). When diagnosed subjectively by neuroradiologists
      however, Bayley scores were not significantly lower in infants with extensive
      diffuse excessive high signal intensity. CONCLUSIONS: These findings lend further
      evidence that diffuse excessive high signal intensity is pathologic and that
      objectively quantified diffusion-based diffuse excessive high signal intensity
      volume at term is associated with cognitive and language impairments. Our
      approach could be used for risk stratification and early intervention for such
      high-risk extremely preterm infants.

PMID- 24138953
TI  - Subependymal giant cell astrocytoma: diagnosis, screening, and treatment.
      Recommendations from the International Tuberous Sclerosis Complex Consensus
      Conference 2012.
AB  - BACKGROUND: Tuberous sclerosis complex is an autosomal dominant disorder
      predisposing to the development of benign lesions in different body organs,
      mainly in the brain, kidney, liver, skin, heart, and lung. Subependymal giant
      cell astrocytomas are characteristic brain tumors that occur in 10% to 20% of
      tuberous sclerosis complex patients and are almost exclusively related to
      tuberous sclerosis complex. Subependymal giant cell astrocytomas usually grow
      slowly, but their progression ultimately leads to the occlusion of the foramen of
      Monro, with subsequent increased intracranial pressure and hydrocephalus, thus
      necessitating intervention. During recent years, secondary to improved
      understanding in the biological and genetic basis of tuberous sclerosis complex,
      mammalian target of rapamycin inhibitors have been shown to be effective in the
      treatment of subependymal giant cell astrocytomas, becoming an alternative
      therapeutic option to surgery. METHODS: In June 2012, an International Tuberous
      Sclerosis Complex Consensus Conference was convened, during which an expert panel
      revised the diagnostic criteria and considered treatment options for subependymal
      giant cell astrocytomas. This article summarizes the subpanel's recommendations
      regarding subependymal giant cell astrocytomas. CONCLUSIONS: Mammalian target of
      rapamycin inhibitors have been shown to be an effective treatment of various
      aspects of tuberous sclerosis complex, including subependymal giant cell
      astrocytomas. Both mammalian target of rapamycin inhibitors and surgery have a
      role in the treatment of subependymal giant cell astrocytomas. Various
      subependymal giant cell astrocytoma-related conditions favor a certain treatment.

PMID- 24138954
TI  - Cystathionine beta-synthase deficiency heralded by cerebral sinus venous
      thrombosis and stroke.
AB  - BACKGROUND: Elevated plasma homocysteine is a risk factor for arterial and venous
      thromboses in adults. Homocysteine is increased in cystathionine beta-synthase
      deficiency, a treatable amino acid metabolic disorder that may be missed on
      newborn screening placing children at risk of thrombosis and strokes. PATIENT: We
      present a 3-year-old girl with normal newborn screening for cystathionine beta
      synthase deficiency who developed a symptomatic cerebral venous sinus thrombosis.
      Subsequent testing revealed marked hyperhomocystinemia and genetic testing
      confirmed cystathionine beta-synthase deficiency. CONCLUSIONS: Current newborn
      screening is limited in its ability to detect cystathionine beta-synthase
      deficiency and although postanalytical interpretation may provide increased
      sensitivity, a normal newborn screening result should not replace the importance
      of physician surveillance.

PMID- 24138955
TI  - Cancer Patient Pathways shortens waiting times and accelerates the diagnostic
      process of suspected sarcoma patients in Denmark.
AB  - Cancer Patient Pathways (CPPs) for suspected cancer were implemented in Denmark
      to reduce waiting times for cancer diagnosis and treatment. Our study describes
      developments in time intervals and tumour size in a natural experiment before and
      after implementation of the CPP for sarcomas (January 1st, 2009). Medical files
      for patients referred with suspected sarcoma from other hospitals to Aarhus
      Sarcoma Centre during 2007-2010 (n=1126) were reviewed for data on milestones,
      time intervals, performed diagnostics, and tumour size. Results showed a
      statistically significant reduction in median number of work days in the phase
      "referral to first appointment" for all patients. For bone sarcomas, median time
      was significantly reduced from 11 to five work days in the phase "first
      appointment to decision of treatment", for soft tissue sarcomas it was reduced
      from 28 to 18 work days in the phase "referral to start of treatment". Passive
      waiting time was reduced, and delays in the fast-track programme were caused
      mostly by supplementary diagnostics. Median tumour size for soft tissue sarcomas
      was reduced from 7.0 to 4.9cm, possibly a secondary effect of increased
      awareness. CPPs have accelerated the diagnostic process for sarcomas, and our
      results may aid international development of similar initiatives. 

PMID- 24138956
TI  - Personality profiles and coping styles in migraine patients with fibromyalgia
      comorbidity.
AB  - Fibromyalgia syndrome (FM) is frequently associated with migraine. In this study
      we aimed to compare personality profiles and coping styles across 23 migraine
      without aura patients sharing FM comorbidity (MWA-FM), 28 migraine without aura
      patients without FM symptoms (MWA) and 51 age- and sex-matched controls, by means
      of Big Five Questionnaire (BFQ) and Coping Orientation to Problem Experienced
      (COPE), and to correlate main results with clinical features. The "Energy"
      personality factor was significantly reduced in patients presenting with FM
      symptoms, compared to both migraine without aura patients and controls. A low
      score in "Dynamism" sub-item with a high score in denial coping style was able to
      distinguish MWA from MW-FM groups with an accuracy of 82.35% (Wilks lambda=0.98;
      chi-square=8.99, DF=1, p=0.005). In particular, lower "Dynamism" scores
      corresponded to a major expression of allodynia, fatigue, anxiety, depression,
      headache frequency and poor quality of sleep and life. Avoidance from active
      coping with stressful events may facilitate worsening of migraine and
      fibromyalgia comorbidity. 

PMID- 24138958
TI  - Human brucellosis at a pig slaughterhouse.
AB  - Seventeen workers in a pig slaughterhouse with signs and symptoms compatible with
      brucellosis were clinically examined at the outpatient service of different
      health institutions and studied by serological tests during the period 2005-2011.
      Eleven blood cultures were taken and six Brucella suis strains were isolated,
      three biovar 1 and three with atypical characteristics. In order to confirm that
      these cases had no common source, a variable number of tandem repeat (VNTR)
      analyses were performed on 5 of the 6 strains whose results showed substantial
      heterogeneity in the genotypes, thereby demonstrating that the immediate origin
      was not the same. Two hundred adult pigs admitted for slaughter at the plant were
      sampled by convenience and tested by buffered antigen plate test (BPAT), serum
      agglutination test (SAT) and 2-mercapto-ethanol test (MET). Seven of 62 males
      (11%) and 25/138 (18%) females tested positive. The study results contribute
      information on risk scenarios for packing plant workers and underscore the need
      to improve plant workers' education on appropriate containment measures and to
      actively screen animals for swine brucellosis. 

PMID- 24138957
TI  - An investigation of the relationship between borderline personality disorder and
      cocaine-related attentional bias following trauma cue exposure: the moderating
      role of gender.
AB  - Elevated rates of borderline personality disorder (BPD) have been found among
      individuals with substance use disorders (SUDs), especially cocaine-dependent
      patients. Evidence suggests that cocaine-dependent patients with BPD are at
      greater risk for negative clinical outcomes than cocaine-dependent patients
      without BPD and BPD-SUD patients dependent on other substances. Despite evidence
      that cocaine-dependent patients with BPD may be at particularly high risk for
      negative SUD outcomes, the mechanisms underlying this risk remain unclear. The
      present study sought to address this gap in the literature by examining cocaine
      related attentional biases among cocaine-dependent patients with (n = 22) and
      without (n = 36) BPD. On separate days, participants listened to both a neutral
      and a personally-relevant emotionally evocative (i.e., trauma-related) script and
      then completed a dot-probe task with cocaine-related stimuli. Findings revealed a
      greater bias for attending to cocaine-related stimuli among male cocaine
      dependent patients with (vs. without) BPD following the emotionally evocative
      script. Study findings suggest the possibility that cocaine use may have gender
      specific functions among SUD patients with BPD, with men with BPD being more
      likely to use cocaine to decrease contextually induced emotional distress. The
      implications of our findings for informing future research on cocaine use among
      patients with BPD are discussed.

PMID- 24138959
TI  - Oscillometric measure of blood pressure detects association between orthostatic
      hypotension and depression in population based study of older adults.
AB  - BACKGROUND: White matter hyperintensities may contribute to depression by
      disrupting neural connections among brain regions that regulate mood. Orthostatic
      hypotension (OH) may be a risk factor for white matter hyperintensities and
      accumulating evidence, although limited suggests it may play a role in the
      development of late-life depression. The aim of this study was to examine the
      relationship between an oscillometric measure of orthostatic hypotension and
      depression in population based sample of older adults. METHODS: We analysed data
      on adults aged 60 and over from the first wave of The Irish Longitudinal Study on
      Ageing (TILDA). Depression was assessed using the Center for Epidemiologic
      Studies--Depression (CES-D) scale and OH was assessed by a sit-to-stand
      orthostatic stress test; two seated blood pressure measurements were followed by
      a single standing blood pressure measurement. Participants self reported whether
      they felt dizzy, light-headed or unsteady on standing. RESULTS: Participants with
      symptomatic OH (SOH, n=20) had the highest mean CES-D score (mean 8.6, SE 1.6)
      when compared to participants with asymptomatic OH (AOH) (mean 5.6, SE .48) and
      participants with no OH (mean 5.2, SE .14) and this difference was significant
      for both comparisons (p<0.001). Linear regression analysis adjusted for socio
      demographic and clinical characteristics showed that SOH was associated with
      higher CES-D scores (unstandardised B coefficient = 2.24; 95% CI .301 - 4.79; p
      =0.05) compared to participants without OH. AOH was not associated with higher
      CES-D scores (unstandardised B coefficient =.162; 95% CI -.681, 1.00; p= 0.70).
      CONCLUSIONS: Symptomatic orthostatic hypotension is associated with depression in
      older adults and needs to be considered in studies examining the relationship
      between vascular disease and depression in older adults.

PMID- 24138960
TI  - Extent of cortical involvement in amyotrophic lateral sclerosis--an analysis
      based on cortical thickness.
AB  - BACKGROUND: Besides the defining involvement of upper and lower motor neurons,
      the involvement of extramotor structures has been increasingly acknowledged in
      amyotrophic lateral sclerosis (ALS). METHODS: Here we investigated a group of 14
      mildly to moderately affected ALS patients and 14 age-matched healthy control
      participants using cortical thickness analysis. Cortical thickness was determined
      from high resolution 3D T1 magnetic resonance images and involved semiautomatic
      segmentation in grey and white matter, cortical alignment and determination of
      thickness using the Laplace method. In addition to a whole-cortex analysis a
      region of interest approach was applied. RESULTS: ALS patients showed regions of
      significant cortical thinning in the pre- and postcentral gyri bilaterally.
      Further regions of cortical thinning included superior and inferior parietal
      lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and
      occipital regions, thus further substantiating extramotor involvement in ALS. A
      relationship between cortical thickness of the right superior frontal cortex and
      clinical severity (assessed by the ALS functional rating scale) was also
      demonstrated. CONCLUSIONS: Cortical thickness is reduced in ALS not only in motor
      areas but in widespread non-motor cortical areas. Cortical thickness is related
      to clinical severity.

PMID- 24138961
TI  - A good idea shot down: taking guns away from the mentally ill won't eliminate
      mass shootings.

PMID- 24138962
TI  - Guns, schools, and mental illness: potential concerns for physicians and mental
      health professionals.
AB  - Since the recent shootings in Tucson, Arizona; Aurora, Colorado; and Newtown,
      Connecticut, there has been an ever-increasing state and national debate
      regarding gun control. All 3 shootings involved an alleged shooter who attended
      college, and in hindsight, evidence of a mental illness was potentially present
      in these individuals while in school. What appears to be different about the
      current round of debate is that both pro-gun control and anti-gun control
      advocates are focusing on mentally ill individuals, early detection of mental
      illness during school years, and the interactions of such individuals with
      physicians and the mental health system as a way to solve gun violence. This
      raises multiple questions for our profession about the apparent increase in these
      types of events, dangerousness in mentally ill individuals, when to intervene
      (voluntary vs involuntary), and what role physicians should play in the debate
      and ongoing prevention. As is evident from the historic Tarasoff court case,
      physicians and mental health professionals often have new regulations/duties,
      changes in the physician-patient relationship, and increased liability resulting
      from high-profile events such as these. Given that in many ways the prediction of
      who will actually commit a violent act is difficult to determine with accuracy,
      physicians need to be cautious with how the current gun debate evolves not only
      for ourselves (eg, increased liability, becoming de facto agents of the state)
      but for our patients as well (eg, increased stigma, erosion of civil liberties,
      and changes in the physician-patient relationship). We provide examples of
      potential troublesome legislation and suggestions on what can be done to improve
      safety for our patients and for the public. 

PMID- 24138963
TI  - Association of coronary artery calcification with hepatic steatosis in
      asymptomatic individuals.
AB  - OBJECTIVE: To determine the association of coronary artery calcification with
      hepatic steatosis in asymptomatic volunteers. PATIENTS AND METHODS: The study
      group comprised 400 asymptomatic volunteers, enrolled from April 1, 2011, to
      September 30, 2012, without known coronary artery disease who were self-referred
      for screening noncontrast computed tomography to determine coronary calcium score
      (CCS). Computed tomographic images were used to determine the presence of hepatic
      steatosis. An a priori model was created to predict a CCS of 100 Agatston units
      (AU) or higher on the basis of Framingham risk factors, diabetes mellitus, and
      metabolic syndrome. Hepatic steatosis was then added to this model. Computation
      of the odds ratio (OR) for hepatic steatosis predicting a CCS of 100 AU or higher
      was performed. Finally, the OR for a CCS of 100 AU or higher being associated
      with hepatic steatosis was calculated. RESULTS: When hepatic steatosis was added
      to traditional coronary risk factors, it was independently associated with a CCS
      of 100 AU or higher (OR, 2.85). This was greater than the OR of Framingham
      factors, diabetes mellitus, or metabolic syndrome. A CCS of 100 AU or higher was
      independently associated with an increased risk for hepatic steatosis (OR, 2.4).
      This OR was higher than traditional hepatic steatosis risk factors or metabolic
      syndrome. CONCLUSION: Hepatic steatosis is a strong independent predictor of a
      CCS of 100 AU or higher in asymptomatic patients. It is associated with an
      increased risk of coronary artery disease beyond that expected from traditional
      coronary risk factors and/or metabolic syndrome. Additional studies are needed to
      clarify the role of hepatic steatosis as a possible independent risk factor for
      the development of coronary artery disease.

PMID- 24138964
TI  - Risky cognitions associated with adolescent alcohol misuse: moral disengagement,
      alcohol expectancies and perceived self-regulatory efficacy.
AB  - AIM: To examine the longitudinal associations between moral disengagement,
      alcohol related expectancies, perceived self-regulatory efficacy and alcohol use
      amongst adolescents. DESIGN AND PARTICIPANTS: A total of 367 students (mean
      age=13.1, SD=0.51; 65% male) from five schools across Sydney, Australia took part
      in this longitudinal study. Participants completed a self-report questionnaire at
      four time points across an 18 month period which assessed their alcohol use,
      levels of moral disengagement, alcohol related expectancies and perceived self
      regulatory efficacy to resist peer pressure to engage in transgressive
      behaviours. RESULTS: Over time, rates of binge drinking in the past three months
      significantly increased, but rates of drinking any alcohol in the past three
      months remained stable. As hypothesised, all three cognitions were independently
      and consistently associated with adolescent alcohol use and binge drinking over
      time, with the exception of perceived self-regulatory efficacy which was not
      associated with an increased risk of drinking any alcohol in the past three
      months when controlling for moral disengagement, alcohol expectancies, gender and
      age. CONCLUSIONS: The current study is the first study to longitudinally map
      three distinct cognitive factors associated with adolescent alcohol use.
      Considering the alarming number of adolescents drinking at levels that place them
      at risk of significant harm, this study has provided important implications about
      cognitive factors that can be targeted to increase the accuracy of assessment and
      efficacy of prevention for alcohol misuse amongst adolescents.

PMID- 24138965
TI  - Coping with jealousy: the association between maladaptive aspects of jealousy and
      drinking problems is mediated by drinking to cope.
AB  - Previous research has shown that both alcohol use and jealousy are related to
      negative relationship outcomes. Little work, however, has examined direct
      associations between alcohol use and jealousy. The current study was aimed to
      build upon existing research examining alcohol use and jealousy. More
      specifically, findings from current jealousy literature indicate that jealousy is
      a multifaceted construct with both maladaptive and adaptive aspects. The current
      study examined the association between maladaptive and adaptive feelings of
      jealousy and alcohol-related problems in the context of drinking to cope. Given
      the relationship between coping motives and alcohol-related problems, our primary
      interest was in predicting alcohol-related problems, but alcohol consumption was
      also investigated. Undergraduate students at a large Northwestern university
      (N=657) in the US participated in the study. They completed measures of jealousy,
      drinking to cope, alcohol use, and alcohol-related problems. Analyses examined
      associations between jealousy subscales, alcohol use, drinking to cope, and
      drinking problems. Results indicated that drinking to cope mediated the
      association between some, but not all, aspects of jealousy and problems with
      alcohol use. In particular, the more negative or maladaptive aspects of jealousy
      were related to drinking to cope and drinking problems, while the more adaptive
      aspects were not, suggesting a more complex view of jealousy than previously
      understood. 

PMID- 24138966
TI  - Tobacco use in older adults in Ghana: sociodemographic characteristics, health
      risks and subjective wellbeing.
AB  - BACKGROUND: Tobacco use over the life-course threatens to increase disease burden
      in older adulthood, including lower income countries like Ghana. This paper
      describes demographic, socioeconomic, health risks and life satisfaction indices
      related to tobacco use among older adults in Ghana. METHODS: This work was based
      on the World Health Organization's multi-country Study on global AGEing and adult
      health (SAGE), conducted in six countries including Ghana. Wave one of SAGE in
      Ghana was conducted in 2007-2008 as collaboration between WHO and the University
      of Ghana Medical School through the Department of Community Health. A nationally
      representative sample of 4305 older adults aged 50 years and above were
      interviewed. Associations between tobacco consumption and sociodemographic,
      socioeconomic, health risk and life satisfaction were evaluated using chi-square
      and odds ratio (OR). Logistic regression analyses, adjusted for age, sex and
      other variables, were conducted to determine predictors of tobacco consumption in
      older persons. RESULTS: Overall prevalence of current daily smokers among older
      adults in Ghana was 7.6%. Tobacco use (i.e. ever used tobacco) was associated
      with older males, (AOR = 1.10, CI 1.05-1.15), older adults residing in rural
      locations (AOR = 1.37, CI 1.083-1.724), and older adults who used alcohol (AOR =
      1.13, CI 0.230-2.418). Tobacco use was also associated (although not
      statistically significant per p-values) with increased self-reporting of angina,
      arthritis, asthma, chronic lung disease, depression, diabetes, hypertension, and
      stroke. Older adults who used tobacco and with increased health risks, tended to
      be without health insurance (AOR = 1.41, CI 1.111-1.787). Satisfaction with life
      and daily living was much lower for those who use tobacco. Regional differences
      existed in tobacco use; the three northern regions (Upper East, Northern and
      Upper West) had higher proportions of tobacco use among older adults in the
      country. Quitting tobacco use was higher in the 70+ years age group, in women,
      among urban residents and in those with at least secondary education. Quitting
      tobacco use also increased with increasing income levels. CONCLUSIONS: Tobacco
      use among older adults in Ghana was associated with older men living in rural
      locations, chronic ill-health and reduced life satisfaction. A high proportion of
      older adults have stopped using tobacco, demonstrating the possibilities for
      effective public health interventions. Health risk reduction strategies through
      targeted anti-smoking health campaigns, improvement in access to health and
      social protection (such as health insurance) will reduce health risks among older
      persons who use tobacco.

PMID- 24138967
TI  - A comparative study of modified confirmatory techniques and additional immuno
      based methods for non-conclusive autolytic bovine spongiform encephalopathy
      cases.
AB  - BACKGROUND: In the framework of the Bovine Spongiform Encephalopathy (BSE)
      surveillance programme, samples with non-conclusive results using the OIE
      confirmatory techniques have been repeatedly found. It is therefore necessary to
      question the adequacy of the previously established consequences of this non
      conclusive result: the danger of failing to detect potentially infected cattle or
      erroneous information that may affect the decision of culling or not of an entire
      bovine cohort. Moreover, there is a very real risk that the underreporting of
      cases may possibly lead to distortion of the BSE epidemiological information for
      a given country.In this study, samples from bovine nervous tissue presenting non
      conclusive results by conventional OIE techniques (Western blot and
      immunohistochemistry) were analyzed. Their common characteristic was a very
      advanced degree of autolysis. All techniques recommended by the OIE for BSE
      diagnosis were applied on all these samples in order to provide a comparative
      study. Specifically, immunohistochemistry, Western blotting, SAF detection by
      electron microscopy and mouse bioassay were compared. Besides, other non
      confirmatory techniques, confocal scanning microscopy and colloidal gold
      labelling of fibrils, were applied on these samples for confirming and improving
      the results. RESULTS: Immunocytochemistry showed immunostaining in agreement with
      the positive results finally provided by the other confirmatory techniques. These
      results corroborated the suitability of this technique which was previously
      developed to examine autolysed (liquified) brain samples. Transmission after
      inoculation of a transgenic murine model TgbovXV was successful in all inocula
      but not in all mice, perhaps due to the very scarce PrPsc concentration present
      in samples.Electron microscopy, currently fallen into disuse, was demonstrated to
      be, not only capable to provide a final diagnosis despite the autolytic state of
      samples, but also to be a sensitive diagnostic alternative for resolving cases
      with low concentrations of PrPsc. CONCLUSIONS: Demonstration of transmission of
      the disease even with low concentrations of PrPsc should reinforce that vigilance
      is required in interpreting results so that subtle changes do not go unnoticed.
      To maintain a continued supervision of the techniques which are applied in the
      routine diagnosis would prove essential for the ultimate eradication of the
      disease.

PMID- 24138968
TI  - Acne: new guidelines help to clarify pediatric management.

PMID- 24138970
TI  - Three tips for top technique: performing the perfect punch.

PMID- 24138971
TI  - An update on chronic wounds and the role of biofilms.
AB  - BACKGROUND: Chronic wounds cause significant morbidity and mortality and cost our
      health care system millions of dollars each year. A major impediment to wound
      healing is the formation of bacterial biofilms. Biofilms are communities of
      bacteria associated with chronic infections. OBJECTIVE: This article reviews the
      literature on chronic wounds and biofilms. The role of biofilms in chronic wounds
      is not widely known. The purpose is to increase awareness of their role and to
      discuss research into novel therapeutic options. METHODS: PubMed searches were
      performed to identify publications on chronic wounds and biofilms. RESULTS:
      Biofilms contribute to chronic wound nonhealing. There is an abundance of
      research into novel antibiofilm strategies for chronic wounds. CONCLUSION:
      Current research is being targeted at antibiofilm strategies needed to restore an
      optimal wound-healing environment. A combined treatment approach involving
      aggressive debridement and the addition of antibiofilm agents is needed.

PMID- 24138972
TI  - Sarcoidosis can present with necrotizing granulomas histologically: two cases of
      ulcerated sarcoidosis and review of the literature.
AB  - BACKGROUND: Sarcoidosis is a systemic inflammatory disorder with cutaneous
      involvement present in 25% of cases. The presence of naked granulomas
      histologically is the hallmark of sarcoidosis. The presence of necrotizing
      granulomas is highly suggestive of other granulomatous conditions and leads the
      clinician to pursue other diagnoses, such as infectious causes. OBJECTIVES: We
      describe two cases of sarcoidosis in which necrotizing granulomas were present on
      biopsy. Both patients had ulcerated cutaneous lesions of sarcoidosis. In one
      case, the presence of these atypical histologic features led to a delay in
      diagnosis of almost 10 years. We review the various histopathologic findings
      associated with cutaneous sarcoidosis and discuss a potential connection between
      ulcerated sarcoidosis and atypical histologic findings. CONCLUSION: When atypical
      histopathologic features are present, the differential diagnosis of sarcoidosis
      should not be excluded.

PMID- 24138973
TI  - Outcomes of wound closure with the reading man flap technique.
AB  - BACKGROUND: In dermatologic surgery, numerous flap types have been described for
      wound closure after skin cancer surgery. The reading man flap was first published
      in 2008 for the closure of skin defects of the face, trunk, and extremities.
      Technically, this flap is based on an asymmetrical Z-plasty. OBJECTIVE: To
      investigate the feasibility, clinical outcomes, and postoperative complications
      for wound closure with the reading man flap technique. METHODS: We treated seven
      patients (facial and extremity defects) after microscopically controlled surgery
      using the reading man flap technique. The median defect size was 491.71 mm2. All
      of the patients were treated under tumescent local anesthesia. RESULTS: A tension
      free defect closure was created in all patients. One minor complication, a wound
      infection on one leg, was observed. CONCLUSION: The described technique is an
      easy and safe dermatologic surgery procedure that can be performed under local
      anesthesia.

PMID- 24138974
TI  - Mobile teledermatology: a promising future in clinical practice.
AB  - BACKGROUND: As a product of electronic health, teledermatology is a cost
      effective means of improving access to care, facilitating specialist
      consultations, and supporting patient self-management. Even so, use of
      traditional teledermatology services is limited by infrastructure and costs in
      the form of digital cameras, computers, and Internet access. METHODS: Considering
      the significant improvement in smartphone camera resolution and the rapidly
      increasing number of physicians using smartphones, we explored the use of
      smartphones as reliable, effective clinical tools in store-and-forward
      teledermatology. We describe the technical specifications of modern smartphone
      cameras, the widespread use of smartphones by physicians, and the advantages of
      smartphones over traditional camera and Internet teledermatology, and we propose
      recommendations as to how mobile teledermatology may be more effectively used in
      modern dermatologic practice.

PMID- 24138975
TI  - Higher frequency of psychiatric morbidity in patients with bacterial infection of
      the skin and subcutaneous tissue versus cutaneous neoplasms: results from a
      nationally representative sample from the United States.
AB  - BACKGROUND: Poor hygiene and nutrition and resultant compromised immune status in
      some psychiatric patients can increase susceptibility to bacterial skin
      infections. OBJECTIVE: We examined the frequency of ICD9-CM psychiatric disorders
      (codes 290-319) in bacterial skin infections (ICD9-CM codes 680-686) (N  = 
      18,734) versus malignant and benign cutaneous neoplasms (ICD9-CM codes 172, 173,
      232, 216) (N  =  8,376), conditions that would be expected to cause psychological
      distress for the patient. METHODS: Logistic regression analysis was conducted
      controlling for age, sex, race, diabetes, obesity, and the use of antineoplastic
      and immunosuppressant medications. RESULTS: Skin infections were more commonly
      (odds ratio  =  3.03, 95% CI 1.58-5.82) associated with a psychiatric disorder;
      the most frequent diagnoses were substance dependence and abuse (19.5%),
      depressive disorder (19.0%), attention-deficit disorder (14.4%), and anxiety
      disorders (11.6%). CONCLUSION: In contrast to cutaneous neoplasms, bacterial skin
      infections were three times as likely to be associated with a psychiatric
      disorder. Psychiatric comorbidity should be ruled out as a factor in patients
      with intractable skin infections.

PMID- 24138976
TI  - Risk of myocardial infarction in canadian patients with psoriasis: a
      retrospective cohort study.
AB  - BACKGROUND: Studies have shown that psoriatic patients are at increased risk for
      myocardial infarction (MI) and stroke. There is a lack of data on MI risk in
      Canadian psoriatic patients. OBJECTIVE: To compare MI risk in Canadian psoriatic
      patients to that in control patients. METHODS: This was a retrospective cohort
      study using Quebec's health insurance database (2005-2010) comparing MI risk in
      psoriatic patients to that in matched controls. Severe psoriasis was defined as
      any diagnosed psoriatic patient who used phototherapy or oral or injectable
      psoriasis treatments. Adjustments were made for several MI risk factors. RESULTS:
      There were 31,421 patients in the psoriasis population, of which 5,159 had severe
      psoriasis. The unadjusted MI incidence rate per 1,000 person-years was 4.88 (95%
      confidence interval [95% CI] 4.50-5.20), 5.58 (95% CI 5.10-6.10), and 5.32 (95%
      CI 4.40-6.40) for the control and mild and severe psoriasis groups, respectively.
      After adjustments, the hazard ratio of MI was significantly higher for psoriatic
      patients than for controls (1.17; 95% CI 1.04-1.31). The hazard ratio was also
      significantly higher than for controls in the mild psoriasis group (1.18; 95% CI
      1.05-1.33) but not in the severe psoriasis group (1.16; 95% CI 0.94-1.42).
      CONCLUSION: The relative MI risk is higher for Canadian psoriatic patients than
      for controls.

PMID- 24138977
TI  - Marjolin ulcer: clinical experience with 34 patients over 15 years.
AB  - BACKGROUND: Malignancies that arise from scars are referred to as Marjolin
      ulcers. The association between chronic ulcers and squamous cell carcinomas is
      well established. There are many case reports in the literature regarding
      Marjolin ulcer; however, randomized controlled clinical series that describe a
      thorough evaluation of these patients are rarely encountered. OBJECTIVE: We
      present our clinic's 15 years of experience with 34 Marjolin ulcer patients and
      their treatment modalities. METHODS: A retrospective analysis of 302 squamous
      cell carcinoma patients who were treated in the plastic surgery department
      between 1997 and 2011 was performed. Thirty-four (10.3%) histopathologically
      confirmed Marjolin ulcer patients were further analyzed. RESULTS: Although burn
      scars represented 77% of the patients in the present study, unstable scars that
      formed following traffic accidents and fistula tracts are also among the commonly
      encountered etiologies. Based on our observations, squamous cell carcinoma, in
      addition to malignant melanoma and verrucous carcinoma, is frequently observed in
      cases of Marjolin ulcers. CONCLUSION: If the goal is to eradicate this clinical
      entity, all of the chronic ulcers that fail to heal require biopsies at regular
      intervals. Large excisional margins, lymphadenectomies in cases of palpable lymph
      nodes, and a well-defined oncology protocol are all essential in treating
      Marjolin ulcer.

PMID- 24138978
TI  - Eruptive melanocytic nevi induced by interferon for nodal metastatic melanoma:
      case report and review of the literature.
AB  - BACKGROUND: The rapid appearance of multiple new melanocytic nevi is known as
      eruptive nevi and has been well documented to occur with certain medications, in
      particular chemotherapeutic agents. METHODS: We report a case of a woman with
      melanoma complicated by nodal metastasis who developed multiple melanocytic nevi
      while on high-dose interferon. RESULTS: Serial photographs confirmed that the
      pigmented lesions were of new onset, whereas histology documented that the
      lesions were dysplastic nevi. A survey of the literature documented numerous
      causes of eruptive nevi, which we review. To date, interferon has not been linked
      to eruptive nevi. CONCLUSIONS: The phenomenon of eruptive nevi has been
      attributed to medications, bullous dermatoses, immunosuppression, and systemic
      conditions and is possibly a paraneoplastic disorder. Interferon appears to be
      another possible cause of this disorder.

PMID- 24138979
TI  - Acute generalized exanthematous pustulosis induced by hydroxychloroquine: first
      case report in Canada and review of the literature.
AB  - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare drug
      eruption presenting with an acute, extensive formation of nonfollicular sterile
      pustules on an erythematous and edematous base. Typically, the rash is
      accompanied by fever and leukocytosis, with spontaneous resolution in < 15 days.
      The incidence of AGEP is estimated at one to five cases per million people per
      year. Only 18% of these are from nonantibiotics. Hydroxychloroquine (HCQ) is an
      antimalarial agent that is also used to treat various dermatologic and
      rheumatologic conditions. OBJECTIVE: We report the first observation in Canada of
      a patient with AGEP induced by HCQ. METHODS AND RESULTS: AGEP was diagnosed in a
      48-year-old female who had been taking HCQ for 2 weeks and then developed a
      diffuse erythematous and edematous pustular eruption. Clinical and pathologic
      findings were consistent with a diagnosis of AGEP. The patient was treated with
      steroids and supportive measures. The rash resolved after 18 days and a
      complicated course in hospital. CONCLUSION: AGEP is a rare drug eruption, usually
      to antibiotics. We report the first case in Canada of AGEP as an adverse reaction
      to HCQ. Clinicians should keep in mind the possibility of this severe skin
      eruption.

PMID- 24138980
TI  - Eruptive squamous cell carcinomas after vemurafenib therapy.
AB  - BACKGROUND: Vemurafenib is an oral BRAF inhibitor recently approved for the
      treatment of metastatic melanoma. Patients treated with this medication have been
      reported to have the occurrence of squamous cell carcinoma (SCC) and/or actinic
      keratosis (AK). OBJECTIVE: We report the case of a patient treated with
      vemurafenib for papillary thyroid carcinoma who subsequently developed multiple
      SCCs and AK of the skin. The lesions were deemed related to the medication and
      treated with excision. In addition, subsequent development of SCCs and AK was
      successfully prevented with a combination of isotretinoin and 5-fluorouracil in
      this patient. We discuss postulated mechanisms for these findings, as well as
      potential preventive therapy with the aforementioned combination regimen in
      patients undergoing treatment with vemurafenib.

PMID- 24138981
TI  - External tissue expander for closing large defects of the extremities and trunk.
AB  - BACKGROUND: Direct closure is the reconstruction of choice for surface soft
      tissue defects; however, it may not be suitable for larger defects due to
      extensive tension. A variety of techniques are available for achieving tension
      free closure, including skin grafts, skin flaps, and internal or external tissue
      expansion. MATERIALS AND METHODS: The external skin expander developed by
      Blomqvist and Steenfos consists of single tissue expander units that contain an
      atraumatic needle and two friction stoppers connected via a silicone string. Each
      device of the expander is inserted under local anaesthesia on each side of the
      defect at a distance of about 2 cm from each other. Postoperative the silicone
      strings have to be tightened at least once a day. After about 5 to 10 days a
      sufficient expansion is achieved and the defect can be closed directly after
      expander removal. RESULTS: The external tissue expander developed by Blomqvist
      and Steenfos is an efficient, time-effective, easy-to-handle device that can be
      inserted under local anesthesia, providing a good functional and satisfactory
      cosmetic outcome. Due to the comparatively low complication rate, even outpatient
      treatment is possible. The major drawback of this technique is the possibility of
      developing uncommon secondary scars under the plastic stoppers.

PMID- 24138982
TI  - Pityriasis rotunda diagnosed in Canada: case presentation and review of the
      literature.
AB  - BACKGROUND: Pityriasis rotunda is a rare cutaneous disorder characterized by
      scaly, circular, well-demarcated, hypo- or hyperpigmented, fine plaques over the
      trunk and extremities. OBJECTIVE: We present a case of pityriasis rotunda in a 44
      year-old African-Canadian woman who presented to a community dermatology practice
      in Toronto. RESULTS: Pityriasis rotunda has been well described in Japan, Italy,
      and South Africa. It is extremely rare in North America, with nine reported cases
      to date, the majority of which were diagnosed in the United States. CONCLUSION:
      Pityriasis rotunda is a rare cutaneous disorder associated with systemic disease.
      To the best of our knowledge, this is the second report of pityriasis rotunda
      diagnosed in Canada.

PMID- 24138983
TI  - Contact dermatitis mimickers: a tertiary care center's experience.
AB  - BACKGROUND: Contact dermatitis (CD) is very common but can be mimicked by
      numerous dermatologic conditions. Thus, a wide differential must be considered
      before a definitive diagnosis of CD is made to ensure the patient receives
      appropriate treatment and follow-up. OBJECTIVE: To describe conditions that can
      present similarly to contact dermatitis. METHODS: We retrospectively analyzed
      patients referred to the Occupational Disease Specialized Program at St.
      Michael's Hospital in Toronto between 2009 and 2011 for CD investigations but
      with a final diagnosis other than CD. RESULTS: We report cases of 2 feet-1 hand
      syndrome, Dermatitis Herpetiformis, Sezary syndrome and two cases of Pityriasis
      Rubra Pilaris misdiagnosed as CD and referred for patch testing at our busy
      tertiary care centre. Failing to recognize these mimickers of CD resulted in a
      significant delay in diagnosis for the patients and resulting initiation of
      necessary intervention. CONCLUSIONS: It is important to consider numerous
      mimickers before making a diagnosis of CD to ensure optimal outcome for patients.

PMID- 24138984
TI  - Cutaneous T-cell lymphoma-like drug eruption in an HIV-positive patient taking
      vancomycin and rifampin.
AB  - BACKGROUND: Cutaneous T-cell pseudolymphoma (CTPL) is a benign reactive T-cell
      lymphoproliferative subtype of pseudolymphoma. Some variants of CTPL can resemble
      the plaques of mycosis fungoides (MF). The vast majority of drug-induced cases
      have been associated with anticonvulsants. There is only one report in the
      literature documenting a case of vancomycin-induced CTPL. METHODS: We report a
      cutaneous T-cell lymphoma-like eruption in a human immunodeficiency virus (HIV)
      positive patient recently started on vancomycin and rifampin. RESULTS: A skin
      biopsy showed several histologic features of MF with immunohistochemical and T
      cell receptor gene rearrangement studies suggestive of CTPL. This atypical T-cell
      reaction mimicking MF completely resolved on cessation of rifampin followed by
      vancomycin. CONCLUSION: Considering drug-induced causes of MF-like histologic
      changes is crucial to prevent unnecessary treatment for MF.

PMID- 24138985
TI  - Synthesis of cobalt nanoparticles on Si (100) by swift heavy ion irradiation.
AB  - We report the growth and characterization of uniform-sized nanoparticles of
      cobalt on n-type silicon (100) substrates by swift heavy ion (SHI) irradiation.
      The Co thin films of 25-nm thicknesses were grown by e-beam evaporation and
      irradiated with two different types of ions, 45-MeV Li3+ and 100-MeV O7+ ions
      with fluences ranging from 1 * 1011 to 1 * 1013 ions/cm2. SHI irradiation, with
      the beam rastered over the area of the film, resulted in the restructuring of the
      film into a dense array of Co nanostructures. Surface topography studied by
      atomic force microscopy revealed narrowed size distributions, with particle sizes
      ranging from 20 to 50 nm, formed through a self-organized process. Ion fluence
      dependent changes in crystallinity of the Co nanostructures were determined by
      glancing angle X-ray diffraction. Rutherford backscattering spectroscopy analysis
      showed the absence of beam-induced mixing in this system. Surface restructuring
      and beam-induced crystallization are the dominant effects, with the nanoparticle
      size and density being dependent on the ion fluence. Results are analyzed in the
      context of molecular dynamics calculations of electron-lattice energy transfer. 

PMID- 24138986
TI  - Pathogenic effects of amyotrophic lateral sclerosis-linked mutation in D-amino
      acid oxidase are mediated by D-serine.
AB  - Amyotrophic lateral sclerosis is a neuromuscular disease characterized by
      selective loss of motor neurons leading to fatal paralysis. We previously
      reported a coding mutation in D-amino acid oxidase (R199W DAO) associated with
      familial amyotrophic lateral sclerosis. DAO metabolizes D-serine, a co-agonist at
      the N-methyl-D-aspartic acid receptor. We investigated the mechanisms mediating
      the pathogenic effects of R199W DAO on motor neuron survival and showed that
      expression of glial R199W DAO is sufficient to induce apoptosis in cocultured
      motor neurons and this is sensitive to 5,7-dichloro-4-hydroxyquinoline-2
      carboxylic acid, an N-methyl-d-aspartic acid receptor antagonist selective for
      the D-serine/glycine site. R199W DAO activates protein aggregation and autophagy,
      which is also sensitive to this antagonist. Using immunocytochemistry, we showed
      that D-serine and DAO were abundant in spinal cord motor neurons and depleted in
      amyotrophic lateral sclerosis. In summary, the toxic effects of R199W DAO on
      motor neurons can be mediated directly by expression in motor neurons or by
      astrocytes in coculture, R199W DAO promotes autophagy and its pathogenic effects
      are at least in part mediated via the N-methyl-d-aspartic acid receptor. 

PMID- 24138987
TI  - ATP-binding cassette transporters P-glycoprotein and breast cancer related
      protein are reduced in capillary cerebral amyloid angiopathy.
AB  - Alzheimer's disease (AD) is the most common form of dementia and marked by
      deposition of amyloid-beta (Abeta) within the brain. Alterations of Abeta
      transporters at the neurovasculature may play a role in the disease process. We
      investigated the expression of ABC transporters P-glycoprotein (P-gp) and breast
      cancer related protein (BCRP) in non-neurologic controls, AD, and severe
      capillary cerebral amyloid angiopathy (capCAA) cases, which are characterized by
      deposition of Abeta within cerebral capillaries. Our data show that microvascular
      expression of P-gp and BCRP is strikingly decreased in capCAA-affected vessels
      but not in AD and control samples. Messenger RNA levels of P-gp, but not of BCRP,
      were downregulated in brain endothelial cells on exposure to oligomeric Abeta42,
      but not fibrillar Abeta42 or Abeta40. Coincubating Abeta42 together with
      clusterin, an amyloid-associated protein highly expressed in capCAA-affected
      vessels, strongly reduced levels of P-gp. In conclusion, accumulation of Abeta,
      in combination with clusterin, within and around cerebral capillaries, may
      further aggravate the disease process in AD by affecting P-gp expression. Loss of
      P-gp expression or activity may serve as a selective biomarker for ongoing
      capCAA.

PMID- 24138988
TI  - SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral
      sclerosis.
AB  - Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in
      patients with amyotrophic lateral sclerosis, accounting for 1.11%-4.92% of
      familial ALS and 2.42%-4.37% of sporadic amyotrophic lateral sclerosis (SALS).
      The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown.
      Three hundred and six patients with SALS from the Department of Neurology, West
      China Hospital of Sichuan University were recruited for this study. From the same
      region, 350 healthy individuals were recruited as a control group. The encoding
      regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous
      mutations- p. I99L, p. D337E, and p. L341V-were identified in 3 patients with
      SALS, none of which were found in healthy controls. The male patient carrying
      mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two
      late-onset patients carrying D337E and p. L341V mutations had bulbar and limb
      onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron
      7 was found in a living male patient with limb onset at age of 62. None of the
      patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget
      disease of bone or mutation of the valosin-containing protein gene. The mutation
      frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than
      those in other racial populations.

PMID- 24138989
TI  - Construction of the influenza A virus infection-induced cell-specific
      inflammatory regulatory network based on mutual information and optimization.
AB  - BACKGROUND: Influenza A virus (IAV) infection-induced inflammatory regulatory
      networks (IRNs) are extremely complex and dynamic. Specific biological
      experiments for investigating the interactions between individual inflammatory
      factors cannot provide a detailed and insightful multidimensional view of IRNs.
      Recently, data from high-throughput technologies have permitted system-level
      analyses. The construction of large and cell-specific IRNs from high-throughput
      data is essential to understanding the pathogenesis of IAV infection. RESULTS: In
      this study, we proposed a computational method, which combines nonlinear ordinary
      differential equation (ODE)-based optimization with mutual information, to
      construct a cell-specific optimized IRN during IAV infection by integrating gene
      expression data with a prior knowledge of network topology. Moreover, we used the
      average relative error and sensitivity analysis to evaluate the effectiveness of
      our proposed approach. Furthermore, from the optimized IRN, we confirmed 45
      interactions between proteins in biological experiments and identified 37 new
      regulatory interactions and 8 false positive interactions, including the
      following interactions: IL1beta regulates TLR3, TLR3 regulates IFN-beta and TNF
      regulates IL6. Most of these regulatory interactions are statistically
      significant by Z-statistic. The functional annotations of the optimized IRN
      demonstrated clearly that the defense response, immune response, response to
      wounding and regulation of cytokine production are the pivotal processes of IAV
      induced inflammatory response. The pathway analysis results from the Kyoto
      Encyclopaedia of Genes and Genomes (KEGG) showed that 8 pathways are enriched
      significantly. The 5 pathways were validated by experiments, and 3 other
      pathways, including the intestinal immune network for IgA production, the
      cytosolic DNA-sensing pathway and the allograft rejection pathway, are the
      predicted novel pathways involved in the inflammatory response. CONCLUSIONS:
      Integration of knowledge-driven and data-driven methods allows us to construct an
      effective IRN during IAV infection. Based on the constructed network, we have
      identified new interactions among inflammatory factors and biological pathways.
      These findings provide new insight into our understanding of the molecular
      mechanisms in the inflammatory network in response to IAV infection. Further
      characterization and experimental validation of the interaction mechanisms
      identified from this study may lead to a novel therapeutic strategy for the
      control of infections and inflammatory responses.

PMID- 24138990
TI  - Frequent concerted genetic mechanisms disrupt multiple components of the NRF2
      inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in thyroid cancer.
AB  - BACKGROUND: Reactive oxygen species contribute to normal thyroid function. The
      NRF2 oxidative response pathway is frequently and constitutively activated in
      multiple tumor types, including papillary thyroid carcinoma (PTC). Genetic
      mechanisms underlying NRF2 pathway activation in PTC are not fully understood.
      Thus, we aimed to determine whether inactivating patterns of DNA-level
      alterations affect genes encoding for individual NRF2 inhibitor complex
      components (CUL3/KEAP1/RBX1) occur in PTC. FINDINGS: Combined patterns of
      epi/genetic alterations for KEAP1/CUL3/RBX1 E3 ubiquitin-ligase complex
      components were simultaneously interrogated for a panel of 310 PTC cases and 40
      adjacent non-malignant tissues. Data were obtained from The Cancer Genome Atlas
      project. Enrichment of NRF2 pathway activation was assessed by gene-set
      enrichment analysis using transcriptome data. Our analyses revealed that PTC
      sustain a strikingly high frequency (80.6%) of disruption to multiple component
      genes of the NRF2 inhibitor complex. Hypermethylation is the predominant
      inactivating mechanism primarily affecting KEAP1 (70.6%) and CUL3 (20%), while
      copy number loss mostly affects RBX1 (16.8%). Concordantly, NRF2-associated gene
      expression signatures are positively and significantly enriched in PTC.
      CONCLUSIONS: The KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex is almost
      ubiquitously affected by multiple DNA-level mechanisms and downstream NRF2
      pathway targets are activated in PTC. Given the importance of this pathway to
      normal thyroid function as well as to cancer; targeted inhibition of NRF2
      regulators may impact strategies for therapeutic intervention involving this
      pathway.

PMID- 24138991
TI  - Recognizing self-regulation.

PMID- 24138992
TI  - Commentary on 'Can sadness alter posture?'.

PMID- 24138993
TI  - Response to "Commentary on 'Can sadness alter posture?'".

PMID- 24138994
TI  - Yoga and social support reduce prenatal depression, anxiety and cortisol.
AB  - The purpose of this study was to compare the effects of yoga (physical activity)
      versus social support (verbal activity) on prenatal and postpartum depression.
      Ninety-two prenatally depressed women were randomly assigned to a yoga or a
      social support control group at 22 weeks gestation. The yoga group participated
      in a 20-min group session (only physical poses) once per week for 12 weeks. The
      social support group (a leaderless discussion group) met on the same schedule. At
      the end of the first and last sessions the yoga group reported less depression,
      anxiety, anger, back and leg pain as compared to the social support group. At the
      end of the last session the yoga group and the support group did not differ. They
      both had lower depression (CES-D), anxiety (STAI), and anger (STAXI) scores and
      improved relationship scores. In addition, cortisol levels decreased for both
      groups following each session. Estriol and progesterone levels decreased after
      the last session. At the postpartum follow-up assessment depression and anxiety
      levels were lower for both groups. 

PMID- 24138995
TI  - Improvements in glucose tolerance with Bikram Yoga in older obese adults: a pilot
      study.
AB  - Bikram yoga is an exotic form of physical activity combining hatha yoga and
      thermal therapy that could positively impact metabolic health. Although this
      increasingly popular alternative exercise may be ideal for obese adults due to
      its low impact nature, few studies have elucidated the health benefits associated
      with it. As an initial step, we determined the effect of Bikram yoga on glucose
      tolerance. Fourteen young lean and 15 older obese subjects completed an 8-week
      Bikram yoga intervention in which classes were completed 3 times per week.
      Glucose tolerance was assessed using a 75 g oral glucose tolerance test. The area
      under the glucose curve following the oral glucose tolerance test was
      significantly reduced as a result of the Bikram Yoga intervention in older obese
      (P < 0.05) but not in young lean subjects. We concluded that a short-term Bikram
      yoga intervention improved glucose tolerance in older obese, but not in young
      lean adults. 

PMID- 24138996
TI  - Incorporating yoga into an intense physical therapy program in someone with
      Parkinson's disease: a case report.
AB  - PURPOSE: The purpose of this case report was to document outcomes following an
      intense exercise program integrating yoga with physical therapy exercise in a
      male with Parkinson's disease. METHOD: The participant performed an intense 11/2
      hour program (Phase A) incorporating strengthening, balance, agility and yoga
      exercises twice weekly for 12 weeks. He then completed a new home exercise
      program developed by the researchers (Phase B) for 12 weeks. RESULTS: His score
      on the Parkinson's Disease Questionnaire improved 16 points while his score on
      the High Level Mobility Assessment tool improved 11 points. There were also
      improvements in muscle length of several lower extremity muscles, in upper and
      lower extremity muscle strength, in dynamic balance and he continues to work full
      time 29 months later. There were no improvements in thoracic posture or aerobic
      power. DISCUSSION: This intense program was an effective dose of exercise for
      someone with Parkinson's disease and allowed him to continue to participate in
      work, leisure, and community activities.

PMID- 24138997
TI  - Effect of an occlusal splint on sleep bruxism in children in a pilot study with a
      short-term follow up.
AB  - The aim of the present study was to evaluate the effect of the use of an occlusal
      splint in children with bruxism in a pilot study with a short-term follow up.
      Seventeen children were recruited, only nine of whom formed the sample following
      the application of the inclusion criteria: presence of sleep bruxism for at least
      six months (based on parents' reports); presence of at least the first permanent
      molars; and no previous history of treatment involving an occlusal splint. The
      sample was submitted to a clinical exam. Other sleep problems were screened with
      the use of a sleep questionnaire filled out by parents before and after 90 days
      of occlusal splint usage. The children received a flat acrylic resin splint with
      full coverage of the occlusal surfaces to be worn in the maxilla. In children
      with erupting teeth, a space was created in the splint to allow normal eruption.
      After the 90-day period, the absence of sleep bruxism and sleep movements was
      noted in most of children. Moreover, snoring was reduced in nearly 50%, which
      raises a new issue to be investigated with regard to the pathophysiology of sleep
      bruxism. The use of an occlusal splint was effective in reducing the symptoms of
      sleep bruxism and other sleep problems. Further investigations should be carried
      out on the relationship between snoring and sleep bruxism in children. 

PMID- 24138998
TI  - The effect of treadmill running on memory before and after the NBM-lesion in
      rats.
AB  - Some studies have shown the effects of exercise training in retarding onset and
      progression of memory deficit in neurodegenerative disorders such as Alzheimer's
      disease. In this research, we investigated the effect of treadmill running on
      memory function; before, after, and continually (before and after) the nucleus
      basalis magnocellularis lesions. 66 male rats were randomly divided into six
      groups, including control, sham operation, the NBM-lesion, exercise before the
      NBM-lesion, exercise after the NBM-lesion, and exercise before and after the NBM
      lesion. Lesion was induced by 5 MUg/MUl bilateral injection of Ibotenic acid.
      Memory function was assessed by using the passive avoidance learning test. Our
      results showed that treadmill running delays cognitive decline in the NBM-lesion
      rats, prevented memory deficit, and has advantageous effects on short-term,
      intermediate and long-term memory. Exercising on a regular basis may impede
      memory loss significantly, which may be attributed to specific molecular pathways
      in the brain. 

PMID- 24138999
TI  - Evaluating the head posture of dentists with no neck pain.
AB  - INTRODUCTION: Dentistry is one of the professions that requires a high degree of
      concentration during the treatment of patients. There are many predisposing
      factors, affecting dentists when working on the patient's teeth, including neck
      flexion, arm abduction and inflexible postural positions, which may put them at
      the risk of developing musculoskeletal disorders related to the neck. Although
      dentists with long records of service show different levels of pain and
      discomfort in their necks, there is no evidence regarding whether younger
      dentists report neck pain before the onset of an abnormal condition in this
      region, including forward head posture (FHP). Discovering any alteration in the
      head posture of dentists might confirm one of the reasons for neck pain in this
      population. MATERIALS: Forty one dentists with no neck pain and forty controls
      having jobs other than dentistry who had no risk factors related to head posture
      voluntarily participated in the present study. A standard method was used to
      measure the cervical curve in these two groups. RESULTS: There was no significant
      difference between the mean values of cervical curve in dentists and the control
      group (p > 0.05). There was also no significant difference between cervical curve
      values in dentists working for either 5-8 years or 8-12 years (p > 0.05). The
      only significant difference was observed in mean cervical curve values of men and
      women in the dentist group (p < 0.05). CONCLUSION: No alteration of cervical
      curve in the dentist group compared to controls might be due to absence of pain
      sensation in the dentists in the current study. In other words, this group might
      have not yet experienced sufficient change in head posture to experience
      significant pain in their neck region.

PMID- 24139000
TI  - Myofascial pain in lateral epicondylalgia: a review.
AB  - BACKGROUND: There is an ongoing debate about the myofascial component,
      characterized by the presence of myofascial trigger points (MTrPs) in lateral
      epicondylalgia (LE). OBJECTIVES: To review current evidence of the association
      between myofascial pain and LE, including efficacy of treatment, focusing on
      myofascial pain. METHODS: PubMed, Google Scholar and PEDro databases were
      searched without search limitations from inception until October 2012 for terms
      relating to LE and MTrPs. RESULTS: Two observational studies showed a high
      prevalence of MTrPs in LE patients compared to healthy controls. Three randomized
      controlled trials demonstrated significant improvement in pain and functional
      outcomes after application of soft tissue techniques, focusing on the myofascial
      component. CONCLUSION: Myofascial pain and MTrPs may be part of the LE etiology.
      Treatment focusing on the myofascial component seems to be effective in reducing
      pain and improving function in patients with LE. Additional trials are essential
      to attain a solid conclusion.

PMID- 24139001
TI  - The effect of muscle energy technique on corticospinal and spinal reflex
      excitability in asymptomatic participants.
AB  - The aim of the current study was to investigate, using a controlled, repeated
      measure design, the neurophysiological responses following an acute bout of
      muscle energy technique (MET). Transcranial magnetic stimulation elicited motor
      evoked potentials using a 110 mm double cone coil placed over the motor area of
      the brain, while Hoffman reflexes (H-reflex) were measured from the posterior
      tibial nerve using electrical stimulation. Responses were measured using surface
      electromyography electrodes placed over the lateral head of the gastrocnemius
      muscle in 12 asymptomatic volunteers. An MET aimed at the lumbosacral joint was
      performed bilaterally. Data were collected pre-intervention, after a control
      intervention, and after the MET intervention. A significant increase was found in
      evoked potential silent period (SP) duration (F2,22 = 7.64; p = 0.03) over time
      following MET, but not the control intervention. A significant decrease was found
      in H-reflex (F1.3,14.4 = 13.8; p = 0.01) over time following the MET
      intervention. MET applied to the lumbosacral joint produced a significant
      decrease in corticospinal and spinal reflex excitability, suggesting overall
      decreased motor excitability. 

PMID- 24139002
TI  - Elimination of intermittent chronic low back pain in a recreational golfer
      following improvement of hip range of motion impairments.
AB  - BACKGROUND: The biomechanical relationship between the hip and low back is well
      described and impairment of hip range of motion is thought to affect lumbar spine
      function, possibly leading to increased loading and subsequent symptoms. However
      therapy for low back pain (LBP) patients is commonly directed solely to the low
      back area overlooking possible hip impairment. CASE DESCRIPTION: A 56-year-old
      male recreational golfer presented with a chronic golf-related low back
      complaint. Previous conservative therapy targeting the spine did not result in
      complete symptom relief. A working diagnosis of L4-S1 facet joint irritation and
      lower lumbar segmental instability secondary to bilateral hip ROM impairment was
      established. A trial of therapy strictly addressing the hip ROM impairments was
      initiated and following 2 treatment sessions, a complete resolution of symptoms
      was achieved and maintained at a 2-month follow-up. DISCUSSION: This case
      demonstrated a complete and rapid relief of un-resolving low back pain with a
      management strategy focused on hip ROM impairments. Clinicians should remember to
      look beyond the local area of complaint and appreciate the interdependent nature
      of the musculoskeletal system.

PMID- 24139003
TI  - The immediate effect of triceps surae myofascial trigger point therapy on
      restricted active ankle joint dorsiflexion in recreational runners: a crossover
      randomised controlled trial.
AB  - OBJECTIVES: To investigate the immediate effect on restricted active ankle joint
      dorsiflexion range of motion (ROM), after a single intervention of myofascial
      trigger point (MTrP) therapy on latent triceps surae MTrPs in recreational
      runners. DESIGN: A crossover randomised controlled trial. PARTICIPANTS: Twenty
      two recreational runners (11 men and 11 women; mean age 24.57; +/-8.7 years) with
      a restricted active ankle joint dorsiflexion and presence of latent MTrPs.
      INTERVENTION: Participants were screened for a restriction in active ankle
      dorsiflexion in either knee flexion (soleus) or knee extension (gastrocnemius)
      and the presence of latent MTrPs. Participants were randomly allocated a week
      apart to both the intervention (combined pressure release and 10 s passive
      stretch) and the control condition. RESULTS: A clinically meaningful (large
      effect size) and statistically significant increase in ankle ROM in the
      intervention compared to the control group was achieved, for the soleus (p =
      0.004) and the gastrocnemius (p = 0.026). CONCLUSION: Apart from the statistical
      significance (p < 0.05), these results are clinically relevant due to the
      immediate increase in ankle dorsiflexion. These results must be viewed in caution
      due to the carry-over effect in the RCT crossover design and the combined MTrP
      therapy approach.

PMID- 24139004
TI  - Low impact weight-bearing exercise in an upright posture achieves greater
      lumbopelvic stability than overground walking.
AB  - The aim of this study was to determine the kinematic differences between
      movements on a new exercise device (EX) that promotes a stable trunk over a
      moving, unstable base of support, and overground walking (OW). Sixteen male
      participants performed EX and OW trials while their movements were tracked using
      a 3D motion capture system. Trunk and pelvis range of motion (ROM) were similar
      between EX and OW in the sagittal and frontal planes, and reduced for EX in the
      transverse plane. The pelvis was tilted anteriorly, on average, by about 16
      degrees  in EX compared to OW. Hip and knee ROM were reduced in EX compared to
      OW. The exercise device appears to promote similar or reduced lumbopelvic motion,
      compared to walking, which could contribute to more tonic activity of the local
      lumbopelvic musculature. 

PMID- 24139005
TI  - The immediate effects of modified Yoga positions on musculoskeletal pain relief.
AB  - Many musculoskeletal pains are related to poor posture. Thus, the aim of the
      present study was to assess the efficiency of a single session of two modified
      Yoga positions with 110 subjects and their 147 pain-related complaints. The
      participants were divided into two groups: The Yoga Group, which received
      treatment of two 20-min postures and the Control Group, which received a placebo
      treatment of 15 min with a turned off ultrasound. All volunteers experienced some
      pain before treatment and were assessed before and after treatment using the
      analog pain scale. A score of 0 indicated no pain whereas 10 was the maximum
      degree of pain on the scale. The difference before and after treatment was
      compared between the groups with a p-value of 0.0001, as measured by the
      Student's t-test. It is possible to conclude that one therapy session is
      effective in the treatment of various musculoskeletal problems. 

PMID- 24139006
TI  - Delayed onset muscle soreness: is massage effective?
AB  - Despite the widespread occurrence of delayed onset muscle soreness (DOMS), there
      is little consensus as to the exact cause or which treatments may be most
      effective at alleviating symptoms. Greater understanding of DOMS can give sports
      medicine and fitness professionals an opportunity to help prevent or speed
      recovery of this performance limiting condition. This article will review the
      DOMS literature, including the potential role of psychosocial factors and explore
      studies which involve massage therapy as a treatment modality. Articles from
      PubMed, MEDLINE, Google Scholar, and references from articles are included in
      this review. Search words and phrases included delayed onset muscle soreness,
      repeated bout effect, massage effectiveness, exercise induced muscle damage, and
      eccentric exercise. 

PMID- 24139007
TI  - The influence of Pilates method in quality of life of practitioners.
AB  - INTRODUCTION: The priority of Pilates is to obtain physical and mental health,
      including flexibility, in a secure and balanced way. AIM: To verify the change in
      the quality of life of practitioners of the Pilates method. METHODOLOGY:
      Descriptive observational study of 74 Pilates practitioners divided into 3
      groups: practitioner for up to three months; practitioner for more than 1 year;
      and ex-practitioners. The quality of life analysis was performed using the self
      administered questionnaire, SF-36. The comparison between groups was made by
      ANOVA one-way, then an analysis by post-hoc Scheffe, with a significance level of
      p < 0.05. RESULT: The group of experienced practitioners showed better results in
      the dimensions of physical function (mean 86.37 points; p < 0.01), general health
      (mean 29.48 points; p < 0.001) and mental health (mean 43.59 points; p < 0.02) of
      quality of life. CONCLUSION: Pilates was associated with the improvement of
      quality of life.

PMID- 24139008
TI  - Massage therapy for essential tremor: quieting the mind.
AB  - BACKGROUND: Essential tremor (ET) is a neurological disorder causing rhythmical
      shaking of part of the body. The condition is known to have an inheritable
      tendency and can present in more than one family member, known as familial
      tremor. Treatment of the disorder is commonly by way of prescription medication.
      ET is progressive and in its mildest form can be sensed and/or observed when
      performing simple motor skills or activities of daily living (ADL). OBJECTIVE: To
      examine the influence of massage therapy on the severity of ET using an activity
      based rating scale pre- and post-treatment. METHODS: The study period included
      five consecutive weekly sessions. The subject, a 63-year-old female, indicated
      her hands and head as the primary areas affected by ET. The treatment aim was to
      reduce sympathetic nervous system firing; therefore, the massage techniques
      implemented were relaxation-based. Methods included Swedish massage,
      hydrotherapy, myofascial release, diaphragmatic breathing, remedial exercise
      education and affirmative symptom management recommendations. Drawings of an
      Archimedes spiral for comparison pre- and post-treatment provided an objective,
      visual representation of tremor intensity affecting fine motor control.
      Goniometric measurements were taken to mark changes in cervical range of motion.
      RESULTS: Tremor intensity decreased after each session; demonstrated by improved
      fine motor skills. The client also reported an increased functionality in
      cervical range, which was documented during the first and last visits.
      CONCLUSION: The results suggest that tremors, symptomatic to ET, can be eased
      through initiatives that encourage a parasympathetic response. Massage therapy
      has shown to be a valuable method of treatment for ET. Tremor severity can
      present in an irregular pattern due to subjective individual triggers; therefore,
      further controlled research is required to lessen the variability between
      subjects and to validate these findings.

PMID- 24139009
TI  - Motor impairment of the ipsilesional body side in poststroke subjects.
AB  - BACKGROUND: In poststroke hemiparetic patients, motor weakness usually occurs on
      the contralesional body side to the brain. Impairment on the ipsilateral body
      side also occurs, but less than the contralateral side. The level and type of
      deficits on the less-affected side is still unclear. Clinicians usually do not
      consider the less-affected side for assessment and management. OBJECTIVE: The
      main purpose is to explore the motor weakness (coordination, gross and fine motor
      dexterity, and muscle strength) of the less-affected side. The secondary aim is
      to determine the relationship between the impairments of both body sides
      (affected and less-affected). METHOD: A prospective, cross-sectional, and
      nonexperimental study was conducted at an outpatient occupational therapy unit of
      a rehabilitation institute. A convenient sample of 27 poststroke (19.0 +/- 14.28
      months) subjects (21 males and 6 females, 22 right-sided and 5 left-sided
      hemiparesis) was recruited. Outcome measures for the less-affected side were
      Minnesota Manual Dexterity Test (MMDT), Purdue PegBoard Test (PPBT) and Manual
      Muscle Testing (MMT). Brunnstrom Recovery Stage (BRS) and Fugl-Meyer Assessment
      (FMA) were applied for the affected side. The less-affected side of the
      poststroke subjects was compared with the side-, age-, and gender-matched
      controls. RESULT: The results showed highly significant (p < 0.001) difference
      between the scores of the ipsilesional body side of the poststroke subjects (MMDT
      = 105.21 +/- 22.70 s, PPBT = 9.30 +/- 2.47, and median MMT grade range from 3 to
      4) and the matched side of the controls (MMDT = 72.41 +/- 11.69 s, PPBT = 13.78
      +/- 1.76, and median MMT grade 5). The findings also suggested no significant
      relation between the motor deficits of the less-affected and affected sides.
      CONCLUSION: The ipsilesional body side of poststroke subjects had impaired
      coordination, gross and fine motor dexterity, and the upper and lower limb muscle
      strength. The side must be assessed and managed accordingly. Management would
      promote motor and functional recovery on both the sides.

PMID- 24139010
TI  - Manual therapy and therapeutic exercise in patient with symptomatic cervical
      spondylotic myelopathy: a case report.
AB  - Cervical spondylotic myelopathy (CSM) is caused by narrowing of the cervical
      spinal canal, although surgical decompression is an obvious indication for spinal
      cord stenosis, there are not enough data to determine that surgery is the most
      indicated intervention for milder forms. The purpose of the present case report
      was to describe the outcomes results of the physical therapy treatment with
      emphasis on manual therapy and therapeutic exercise for a patient with CSM. A 58
      year-old male patient attended the physical therapy clinic due to pain and
      paresthesia in the upper and lower limbs. The magnetic resonance imaging was
      compatible with spondylotic myelopathy. Following physical therapy treatment, the
      patient exhibited an improvement in functional capacity (triangle step test and
      timed 10-m walk), pain, paresthesia, mJOA scale and Neck Disability Index. Based
      on the lack of rapid evolution of neurological impairment, physical therapy
      treatment was indicated, which achieved satisfactory results. 

PMID- 24139011
TI  - The Fourth Phase of Water: a role in fascia?

PMID- 24139012
TI  - The anatomical and functional relation between gluteus maximus and fascia lata.
AB  - There is not full agreement regarding the distal insertions of the gluteus
      maximus muscle (GM), particularly the insertions into the iliotibial band and
      lateral intermuscular septum. 6 cadavers, 4 males and 2 females, mean age 69 yr,
      were dissected to evaluate the insertions of the GM into the iliotibial band,
      fascia lata, lateral intermuscular septum and femur. The iliotibial band is a
      reinforcement of the fascia lata and cannot be separated from it. Its inner side
      is in continuity with the lateral intermuscular septum, which divides the
      quadriceps from the hamstring. In all subjects the gluteus maximus presented a
      major insertion into the fascia lata, so large that the iliotibial tract could be
      considered a tendon of insertion of the gluteus maximus. The fascial insertion of
      the gluteus maximus muscle could explain the transmission of the forces from the
      thoracolumbar fascia to the knee. 

PMID- 24139013
TI  - Whole body vibration therapy for painful diabetic peripheral neuropathy: a pilot
      study.
AB  - The unsatisfactory results associated with conventional treatments for symptoms
      of diabetic peripheral neuropathy (DPN) demonstrate a need for research into
      alternative therapies. The purpose of this study was to determine the efficacy of
      whole body vibration therapy (WBV) as a treatment for pain associated with DPN.
      Participants (n = 8) with painful DPN received three treatment sessions per week
      for four weeks. Each session consisted of four bouts of 3 min of vibration
      (frequency 25 Hz, amplitude 5 mm). The primary outcome measures were changes in
      the visual analog pain scale (VAS) and changes in the neuropathic pain scale
      (NPS). WBV demonstrated a significant (p < 0.05) acute pain reduction in the VAS,
      and a significant chronic reduction in both the VAS and NPS scales. No side
      effects were observed during this study. WBV appears to be an effective, non
      invasive treatment for pain associated with DPN. 

PMID- 24139014
TI  - Ultrasound characteristics of the lateral retinaculum in 10 patients with
      patellofemoral pain syndrome compared to healthy controls.
AB  - BACKGROUND: Histopathologic changes of the lateral retinaculum are described in
      patients with patellofemoral pain syndrome (PFPS). No information is available on
      the presence of structural changes of the lateral retinaculum on ultrasound
      examination in patients with PFPS. PURPOSE: To describe ultrasound
      characteristics and colour Doppler findings in patients with unilateral PFPS and
      in healthy controls. METHODS: 10 patients with unilateral PFPS and 10 healthy
      control subjects underwent ultrasound and colour Doppler examination of the
      lateral retinaculum of both knees. Thickness of the lateral retinaculum was
      measured at three predefined locations. In addition presence of
      neovascularisation was assessed. RESULTS: Thickness of the lateral retinaculum of
      both affected (mean [SD] of three locations 4.0 [1.4] mm, 95%CI: 1.2-6.8) and
      asymptomatic (3.7 [0.8] mm, 95%CI: 2.1-5.3) knees was increased in the patient
      group compared to the control subjects (3.0 [0.1] mm, 95%CI: 2.8-3.2), although
      not reaching statistical significance. Positive colour Doppler signals of the
      lateral retinaculum were found in 4 patients and in none of the control subjects
      (4/10 versus 0/10; 2 * 2 Fisher's exact test 1-tailed p = 0.0433; 2-tailed p =
      0.0866; mid p value = 0.0217). CONCLUSIONS: The results of these measurements
      indicate a trend towards a larger thickness of the lateral retinaculum and showed
      neovascularisation measured by ultrasound and colour Doppler examination in
      patients with PFPS. The larger thickness of the lateral retinaculum on ultrasound
      examination was found in both affected and in asymptomatic knees of the patients,
      supporting the concept that PFPS is a bilateral rather than a unilateral
      disorder. Further research is needed to unravel the role of the lateral
      retinaculum in pathogenesis of PFPS and to clarify the role of the lateral
      retinaculum as a target for therapy in patients with PFPS.

PMID- 24139015
TI  - Contextualising the core.

PMID- 24139016
TI  - Facilitating change through active rehabilitation techniques.

PMID- 24139017
TI  - 'The core': understanding it, and retraining its dysfunction.
AB  - "Core stability training" is popular in both the therapeutic and fitness
      industries but what is actually meant and understood by this concept? And does
      everyone need the same training approach? This paper examines the landscape of
      'the core' and its control from both a clinical and research perspective. It
      attempts a comprehensive review of its healthy functional role and how this is
      commonly changed in people with spinal and pelvic girdle pain syndromes. The
      common clinically observable and palpable patterns of functional and structural
      change associated with 'problems with the core' have been relatively little
      described. This paper endeavors to do so, introducing a variant paradigm aimed at
      promoting the understanding and management of these altered patterns of 'core
      control'. Clinically, two basic subgroups emerge. In light of these, the
      predictable difficulties that each group finds in establishing the important
      fundamental elements of spino-pelvic 'core control' and how to best retrain
      these, are highlighted. The integrated model presented is applicable for
      practitioners re-educating movement in physiotherapy, rehabilitation, Pilates,
      Yoga or injury prevention within the fitness industry in general. 

PMID- 24139018
TI  - The lateral squat.

PMID- 24139019
TI  - Does a palliative care consult decrease the cost of caring for hospitalized
      patients with dementia?
AB  - OBJECTIVE: Advanced dementia (AD) is a terminal disease. Palliative care is
      increasingly becoming of critical importance for patients afflicted with AD. The
      primary objective of this study was to compare pharmacy cost before and after a
      palliative care consultation (PCC) in patients with end-stage dementia. A
      secondary objective was to investigate the cost of particular types of medication
      before and after a PCC. METHOD: This was a retrospective study of 60 hospitalized
      patients with end-stage dementia at a large academic tertiary care hospital from
      January 1, 2010 to October 1, 2011, in order to investigate pharmacy costs before
      and after a PCC. In addition to demographics, we carried out a comparison of the
      average daily pharmacy cost and comparison of the proportion of subjects taking
      each medication type (cardiac, analgesics, antibiotics, antipsychotics and
      antiemetics) before and after a PCC. RESULTS: There was a significant decrease in
      overall average daily pharmacy cost from before to after a PCC ($31.16 +/- 24.71
      vs. $20.83 +/- 19.56; p < 0.003). There was also a significant difference in the
      proportion of subjects taking analgesics before and after PCC (55 vs. 73.3%; p <
      0.009), with a significant average daily analgesic cost rise from pre- to post
      PCC: $1.36 +/- 5.07 (median = $0.05) versus. $2.35 +/- 5.35 (median = $0.71),
      respectively, p < 0.011; average daily antiemetics cost showed a moderate
      increase from pre- to post-PCC: $0.08 +/- 0.37 (median = $0) versus $0.23 +/-
      0.75 (median = $0), respectively, p < 0.047. SIGNIFICANCE OF RESULTS: Our
      findings indicate that PCC is associated with overall decreased medication cost
      in hospitalized AD patients. Additionally, receiving a PCC was related to greater
      use of pain medications in hospitalized dementia patients. Our study corroborates
      the benefits of palliative care team intervention in managing elderly
      hospitalized dementia patients.

PMID- 24139020
TI  - Quantification of guided mode propagation in fractured long bones.
AB  - Guided modes propagation in intact, fractured and healing long bone has drawn
      significant research interests. However, mode quantifications for the direct
      comparison are still necessary to address. The aim of the study is to analyze the
      mode interaction with a notch-fracture in the long bone and find quantitative
      ultrasound parameters sensitive to depth and width variation of the fracture. We
      analyzed the impacts of the partially and completely diaphyseal osteotomy on
      fundamental guided modes propagation using the two-dimension finite-difference
      time-domain (2D-FDTD) simulations. The long bones were built as three layer
      models by a cortical plate embedded between overlying soft tissue and inner
      coated marrow. Narrowband low-frequency sinusoids (100 kHz) were employed to only
      excite two fundamental guided modes. The mode amplitude variations were
      investigated as functions of the gap-breakage width and depth. It is found that
      the transverse fractures have strong influences on the anti-symmetric mode A0
      transmission and reflection, whereas amplitudes of the symmetric mode S0 are not
      sensitive to the fracture degree. The quantitative results consistently indicate
      that reflection energy and transmission coefficients of the S0 and A0 modes can
      be used to quantify the mode interaction in the fractured long bone and further
      to evaluate long bone fracture status. Future study is needed to investigate the
      physical experiments on realistic fractured long bone and to insure that the
      proposed ultrasound parameters can be used to quantitatively evaluate the long
      bone fracture in clinical application.

PMID- 24139021
TI  - Cloud based intelligent system for delivering health care as a service.
AB  - The promising potential of cloud computing and its convergence with technologies
      such as mobile computing, wireless networks, sensor technologies allows for
      creation and delivery of newer type of cloud services. In this paper, we advocate
      the use of cloud computing for the creation and management of cloud based health
      care services. As a representative case study, we design a Cloud Based
      Intelligent Health Care Service (CBIHCS) that performs real time monitoring of
      user health data for diagnosis of chronic illness such as diabetes. Advance body
      sensor components are utilized to gather user specific health data and store in
      cloud based storage repositories for subsequent analysis and classification. In
      addition, infrastructure level mechanisms are proposed to provide dynamic
      resource elasticity for CBIHCS. Experimental results demonstrate that
      classification accuracy of 92.59% is achieved with our prototype system and the
      predicted patterns of CPU usage offer better opportunities for adaptive resource
      elasticity. 

PMID- 24139022
TI  - Longitudinal in vivo muscle function analysis of the DMSXL mouse model of
      myotonic dystrophy type 1.
AB  - Myotonic dystrophy is the most common adult muscle dystrophy. In view of emerging
      therapies, which use animal models as a proof of principle, the development of
      reliable outcome measures for in vivo longitudinal study of mouse skeletal muscle
      function is becoming crucial. To satisfy this need, we have developed a device to
      measure ankle dorsi- and plantarflexion torque in rodents. We present an in vivo
      8-month longitudinal study of the contractile properties of the skeletal muscles
      of the DMSXL mouse model of myotonic dystrophy type 1. Between 4 and 12 months of
      age, we observed a reduction in muscle strength in the ankle dorsi- and
      plantarflexors of DMSXL compared to control mice although the strength per muscle
      cross-section was normal. Mild steady myotonia but no abnormal muscle fatigue was
      also observed in the DMSXL mice. Magnetic resonance imaging and histological
      analysis performed at the end of the study showed respectively reduced muscle
      cross-section area and smaller muscle fibre diameter in DMSXL mice. In
      conclusion, our study demonstrates the feasibility of carrying out longitudinal
      in vivo studies of muscle function over several months in a mouse model of
      myotonic dystrophy confirming the feasibility of this method to test preclinical
      therapeutics.

PMID- 24139023
TI  - Amygdala volume linked to individual differences in mental state inference in
      early childhood and adulthood.
AB  - We investigated the role of the amygdala in mental state inference in a sample of
      adults and in a sample of children aged 4 and 6 years. This period in early
      childhood represents a time when mentalizing abilities undergo dramatic changes.
      Both children and adults inferred mental states from pictures of others' eyes,
      and children also inferred the mental states of others from stories (e.g., a
      false belief task). We also collected structural MRI data from these
      participants, to determine whether larger amygdala volumes (controlling for age
      and total gray matter volume) were related to better face-based and story-based
      mentalizing. For children, larger amygdala volumes were related to better face
      based, but not story-based, mentalizing. In contrast, in adults, amygdala volume
      was not related to face-based mentalizing. We next divided the face-based items
      into two subscales: cognitive (e.g., thinking, not believing) versus affective
      (e.g., friendly, kind) items. For children, performance on cognitive items was
      positively correlated with amygdala volume, but for adults, only performance on
      affective items was positively correlated with amygdala volume. These results
      indicate that the amygdala's role in mentalizing may be specific to face-based
      tasks and that the nature of its involvement may change over development. 

PMID- 24139024
TI  - Enhanced XAO: the ontology of Xenopus anatomy and development underpins more
      accurate annotation of gene expression and queries on Xenbase.
AB  - BACKGROUND: The African clawed frogs Xenopus laevis and Xenopus tropicalis are
      prominent animal model organisms. Xenopus research contributes to the
      understanding of genetic, developmental and molecular mechanisms underlying human
      disease. The Xenopus Anatomy Ontology (XAO) reflects the anatomy and
      embryological development of Xenopus. The XAO provides consistent terminology
      that can be applied to anatomical feature descriptions along with a set of
      relationships that indicate how each anatomical entity is related to others in
      the embryo, tadpole, or adult frog. The XAO is integral to the functionality of
      Xenbase (http://www.xenbase.org), the Xenopus model organism database. RESULTS:
      We significantly expanded the XAO in the last five years by adding 612 anatomical
      terms, 2934 relationships between them, 640 synonyms, and 547 ontology cross
      references. Each term now has a definition, so database users and curators can be
      certain they are selecting the correct term when specifying an anatomical entity.
      With developmental timing information now asserted for every anatomical term, the
      ontology provides internal checks that ensure high-quality gene expression and
      phenotype data annotation. The XAO, now with 1313 defined anatomical and
      developmental stage terms, has been integrated with Xenbase expression and
      anatomy term searches and it enables links between various data types including
      images, clones, and publications. Improvements to the XAO structure and
      anatomical definitions have also enhanced cross-references to anatomy ontologies
      of other model organisms and humans, providing a bridge between Xenopus data and
      other vertebrates. The ontology is free and open to all users. CONCLUSIONS: The
      expanded and improved XAO allows enhanced capture of Xenopus research data and
      aids mechanisms for performing complex retrieval and analysis of gene expression,
      phenotypes, and antibodies through text-matching and manual curation. Its
      comprehensive references to ontologies across taxa help integrate these data for
      human disease modeling.

PMID- 24139025
TI  - The downs and ups of sensory deprivation: evidence for firing rate homeostasis in
      vivo.
AB  - Homeostatic adjustment of neuronal firing rates is considered a vital mechanism
      to keep neurons operating in their optimal range despite dynamically changing
      input. Two studies in this issue of Neuron, Hengen et al. (2013) and Keck et al.
      (2013), provide evidence for firing rate homeostasis in the neocortex of freely
      behaving rodents.

PMID- 24139026
TI  - ADAM10 prodomain mutations cause late-onset Alzheimer's disease: not just the
      latest FAD.
AB  - In this issue of Neuron, Suh et al. (2013) describe two rare ADAM10 prodomain
      mutations that cause late-onset Alzheimer's disease by impairing prodomain
      chaperone function, attenuating alpha-secretase activity, and reducing adult
      hippocampal neurogenesis. These results support both ADAM10 as a therapeutic
      target and the amyloid hypothesis of Alzheimer's disease.

PMID- 24139027
TI  - Anti-tau antibodies: hitting the target.
AB  - Immunotherapies targeting tau in mouse models of human tauopathies could have
      disease-modifying effects. In this issue of Neuron, Yanamandra et al. (2013) use
      tau antibodies, which effectively block tau seeding in culture, to attenuate
      tauopathy and improve cognition in mutant tau mouse models.

PMID- 24139028
TI  - C9orf72-associated FTD/ALS: when less is more.
AB  - Hexanucleotide repeat expansions in C9ORF72 cause neurodegeneration in FTD and
      ALS by unknown mechanisms. A new report, by Donnelly et al. (2013), finds that
      these repeats trigger a pathogenic gain-of-function cascade that can be corrected
      by suppressing expression of the repeat transcript, paving the way for
      therapeutic strategies aimed at eliminating the toxic RNA.

PMID- 24139029
TI  - Progenitor networking in the fetal primate neocortex.
AB  - Basal radial glia (bRG) is a recently identified major type of neural stem cell
      in fetal primate, notably human, neocortex. In this issue of Neuron, Betizeau et
      al. (2013) now demonstrate that four morphologically distinct bRG subtypes exist
      in the outer subventricular zone of fetal macaque neocortex, and reveal an
      unexpected complexity of lineages generating neurons.

PMID- 24139030
TI  - The declaration of independence of the neurovascular intimacy.
AB  - In this issue of Neuron, Oh and Gu (2013) present a model in which intimately
      related embryonic nerves and blood vessels are patterned independently in
      response to different guidance cues from a central organizer: the whisker. 

PMID- 24139031
TI  - Of mice and men: what physiological correlates of cognitive deficits in a mouse
      model of schizophrenia tell us about psychiatric disease.
AB  - Hippocampal neurons "replay" activity related to previous events during rest. In
      this issue of Neuron, Suh et al. (2013) show that this physiological correlate of
      learning is impaired in mice lacking calcineurin, establishing a link between
      synaptic anomalies and cognitive deficits observed in this schizophrenia model.

PMID- 24139032
TI  - The challenge of connecting the dots in the B.R.A.I.N.
AB  - The Brain Research through Advancing Innovative Neurotechnologies (BRAIN)
      Initiative has focused scientific attention on the necessary tools to understand
      the human brain and mind. Here, we outline our collective vision for what we can
      achieve within a decade with properly targeted efforts and discuss likely
      technological deliverables and neuroscience progress. 

PMID- 24139033
TI  - How to pick a graduate advisor.
AB  - In this NeuroView, I provide a guide for young scientists on how to select a
      graduate advisor or postdoctoral advisor. Good mentorship is not only pivotal for
      career success, but it is pivotal for driving innovation and for the health of
      our universities. Universities need to do much more to teach faculty how to
      mentor and to ensure mentoring quality. I propose an M-index to measure mentoring
      quality. I also call here for better studies of what great mentorship entails,
      better reward for great mentors, and more consideration of mentoring quality when
      awarding prizes and grants. 

PMID- 24139034
TI  - Noncanonical roles of voltage-gated sodium channels.
AB  - The Hodgkin-Huxley formulation, at its 60th anniversary, remains a bastion of
      neuroscience. Sodium channels Nav1.1-Nav1.3 and Nav1.6-Nav1.9 support
      electrogenesis in neurons and are often considered "neuronal," whereas Nav1.4 and
      Nav1.5 drive electrogenesis in skeletal and cardiac muscle. These channels are,
      however, expressed in cell types that are not considered electrically excitable.
      Here, we discuss sodium channel expression in diverse nonexcitable cell types,
      including astrocytes, NG2 cells, microglia, macrophages, and cancer cells, and
      review evidence of noncanonical roles, including regulation of effector functions
      such as phagocytosis, motility, Na(+)/K(+)-ATPase activity, and metastatic
      activity. Armed with powerful techniques for monitoring channel activity and for
      real-time assessment of [Na(+)]i and [Ca(2+)]i, neuroscientists are poised to
      expand the understanding of noncanonical roles of sodium channels in healthy and
      diseased tissues. 

PMID- 24139035
TI  - Kainate receptors in health and disease.
AB  - Our understanding of the molecular properties of kainate receptors and their
      involvement in synaptic physiology has progressed significantly over the last 30
      years. A plethora of studies indicate that kainate receptors are important
      mediators of the pre- and postsynaptic actions of glutamate, although the
      mechanisms underlying such effects are still often a topic for discussion. Three
      clear fields related to their behavior have emerged: there are a number of
      interacting proteins that pace the properties of kainate receptors; their
      activity is unconventional since they can also signal through G proteins,
      behaving like metabotropic receptors; they seem to be linked to some devastating
      brain diseases. Despite the significant progress in their importance in brain
      function, kainate receptors remain somewhat puzzling. Here we examine discoveries
      linking these receptors to physiology and their probable implications in disease,
      in particular mood disorders, and propose some ideas to obtain a deeper
      understanding of these intriguing proteins. 

PMID- 24139037
TI  - Synaptic scaling and homeostatic plasticity in the mouse visual cortex in vivo.
AB  - Homeostatic plasticity is important to maintain a set level of activity in
      neuronal circuits and has been most extensively studied in cell cultures
      following activity blockade. It is still unclear, however, whether activity
      changes associated with mechanisms of homeostatic plasticity occur in vivo, for
      example after changes in sensory input. Here, we show that activity levels in the
      visual cortex are significantly decreased after sensory deprivation by retinal
      lesions, followed by a gradual increase in activity levels in the 48 hr after
      deprivation. These activity changes are associated with synaptic scaling,
      manifested in vitro by an increase in mEPSC amplitude and in vivo by an increase
      in spine size. Together, these data show that homeostatic activity changes occur
      in vivo in parallel with synaptic scaling.

PMID- 24139036
TI  - Goals and habits in the brain.
AB  - An enduring and richly elaborated dichotomy in cognitive neuroscience is that of
      reflective versus reflexive decision making and choice. Other literatures refer
      to the two ends of what is likely to be a spectrum with terms such as goal
      directed versus habitual, model-based versus model-free or prospective versus
      retrospective. One of the most rigorous traditions of experimental work in the
      field started with studies in rodents and graduated via human versions and
      enrichments of those experiments to a current state in which new paradigms are
      probing and challenging the very heart of the distinction. We review four
      generations of work in this tradition and provide pointers to the forefront of
      the field's fifth generation. 

PMID- 24139038
TI  - Firing rate homeostasis in visual cortex of freely behaving rodents.
AB  - It has been postulated that homeostatic mechanisms maintain stable circuit
      function by keeping neuronal firing within a set point range, but such firing
      rate homeostasis has never been demonstrated in vivo. Here we use chronic
      multielectrode recordings to monitor firing rates in visual cortex of freely
      behaving rats during chronic monocular visual deprivation (MD). Firing rates in
      V1 were suppressed over the first 2 day of MD but then rebounded to baseline over
      the next 2-3 days despite continued MD. This drop and rebound in firing was
      accompanied by bidirectional changes in mEPSC amplitude measured ex vivo. The
      rebound in firing was independent of sleep-wake state but was cell type specific,
      as putative FS and regular spiking neurons responded to MD with different time
      courses. These data establish that homeostatic mechanisms within the intact CNS
      act to stabilize neuronal firing rates in the face of sustained sensory
      perturbations.

PMID- 24139039
TI  - Blocking endocytosis enhances short-term synaptic depression under conditions of
      normal availability of vesicles.
AB  - It is commonly thought that clathrin-mediated endocytosis is the rate-limiting
      step of synaptic transmission in small CNS boutons with limited capacity for
      synaptic vesicles, causing short-term depression during high rates of synaptic
      transmission. Here, we show by analyzing synaptopHluorin fluorescence that 200
      action potentials evoke the same cumulative amount of vesicle fusion,
      irrespective of the frequency of stimulation (5-40 Hz), implying the absence of
      vesicle reuse, since the method used (alkaline-trapping) measures only first
      round exocytosis. After blocking all slow or specifically clathrin-mediated
      endocytosis, however, the same stimulation patterns cause a rapid stimulation
      frequency-dependent release depression. This form of depression does not reflect
      insufficient vesicle supply, but appears to be the result of slow clearance of
      vesicular components from the release site. Our findings uncover an important yet
      overlooked role of endocytic proteins for release site clearance in addition to
      their well-characterized role in endocytosis itself.

PMID- 24139040
TI  - Subthreshold mechanisms underlying state-dependent modulation of visual
      responses.
AB  - The processing of sensory information varies widely across behavioral states.
      However, little is known about how behavioral states modulate the intracellular
      activity of cortical neurons to effect changes in sensory responses. Here, we
      performed whole-cell recordings from neurons in upper-layer primary visual cortex
      of awake mice during locomotion and quiet wakefulness. We found that the signal
      to-noise ratio for sensory responses was improved during locomotion by two
      mechanisms: (1) a decrease in membrane potential variability leading to a
      reduction in background firing rates and (2) an enhancement in the amplitude and
      reliability of visually evoked subthreshold responses mediated by an increase in
      total conductance and a depolarization of the stimulus-evoked reversal potential.
      Consistent with the enhanced signal-to-noise ratio for visual responses during
      locomotion, we demonstrate that performance is improved in a visual detection
      task during this behavioral state. 

PMID- 24139041
TI  - In vivo expression of a light-activatable potassium channel using unnatural amino
      acids.
AB  - Optical control of protein function provides excellent spatial-temporal
      resolution for studying proteins in situ. Although light-sensitive exogenous
      proteins and ligands have been used to manipulate neuronal activity, a method for
      optical control of neuronal proteins using unnatural amino acids (Uaa) in vivo is
      lacking. Here, we describe the genetic incorporation of a photoreactive Uaa into
      the pore of an inwardly rectifying potassium channel Kir2.1. The Uaa occluded the
      pore, rendering the channel nonconducting, and, on brief light illumination, was
      released to permit outward K(+) current. Expression of this photoinducible
      inwardly rectifying potassium (PIRK) channel in rat hippocampal neurons created a
      light-activatable PIRK switch for suppressing neuronal firing. We also expanded
      the genetic code of mammals to express PIRK channels in embryonic mouse neocortex
      in vivo and demonstrated a light-activated PIRK current in cortical neurons.
      These principles could be generally expanded to other proteins expressed in the
      brain to enable optical regulation.

PMID- 24139042
TI  - RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense
      intervention.
AB  - A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72
      gene is the most common genetic abnormality in familial and sporadic amyotrophic
      lateral sclerosis (ALS) and frontotemporal dementia (FTD). The function of the
      C9ORF72 protein is unknown, as is the mechanism by which the repeat expansion
      could cause disease. Induced pluripotent stem cell (iPSC)-differentiated neurons
      from C9ORF72 ALS patients revealed disease-specific (1) intranuclear GGGGCCexp
      RNA foci, (2) dysregulated gene expression, (3) sequestration of GGGGCCexp RNA
      binding protein ADARB2, and (4) susceptibility to excitotoxicity. These
      pathological and pathogenic characteristics were confirmed in ALS brain and were
      mitigated with antisense oligonucleotide (ASO) therapeutics to the C9ORF72
      transcript or repeat expansion despite the presence of repeat-associated non-ATG
      translation (RAN) products. These data indicate a toxic RNA gain-of-function
      mechanism as a cause of C9ORF72 ALS and provide candidate antisense therapeutics
      and candidate human pharmacodynamic markers for therapy. 

PMID- 24139043
TI  - Deficiency of asparagine synthetase causes congenital microcephaly and a
      progressive form of encephalopathy.
AB  - We analyzed four families that presented with a similar condition characterized
      by congenital microcephaly, intellectual disability, progressive cerebral
      atrophy, and intractable seizures. We show that recessive mutations in the ASNS
      gene are responsible for this syndrome. Two of the identified missense mutations
      dramatically reduce ASNS protein abundance, suggesting that the mutations cause
      loss of function. Hypomorphic Asns mutant mice have structural brain
      abnormalities, including enlarged ventricles and reduced cortical thickness, and
      show deficits in learning and memory mimicking aspects of the patient phenotype.
      ASNS encodes asparagine synthetase, which catalyzes the synthesis of asparagine
      from glutamine and aspartate. The neurological impairment resulting from ASNS
      deficiency may be explained by asparagine depletion in the brain or by
      accumulation of aspartate/glutamate leading to enhanced excitability and neuronal
      damage. Our study thus indicates that asparagine synthesis is essential for the
      development and function of the brain but not for that of other organs. 

PMID- 24139044
TI  - Precursor diversity and complexity of lineage relationships in the outer
      subventricular zone of the primate.
AB  - Long-term ex vivo live imaging combined with unbiased sampling of cycling
      precursors shows that macaque outer subventricular zone (OSVZ) includes four
      distinct basal radial glial (bRG) cell morphotypes, bearing apical and/or basal
      processes in addition to nonpolar intermediate progenitors (IPs). Each of the
      five precursor types exhibits extensive self-renewal and proliferative capacities
      as well as the ability to directly generate neurons, albeit with different
      frequencies. Cell-cycle parameters exhibited an unusual stage-specific regulation
      with short cell-cycle duration and increased rates of proliferative divisions
      during supragranular layer production at late corticogenesis. State transition
      analysis of an extensive clonal database reveals bidirectional transitions
      between OSVZ precursor types as well as stage-specific differences in their
      progeny and topology of the lineage relationships. These results explore rodent
      primate differences and show that primate cortical neurons are generated through
      complex lineages by a mosaic of precursors, thereby providing an innovative
      framework for understanding specific features of primate corticogenesis.

PMID- 24139045
TI  - Establishment of neurovascular congruency in the mouse whisker system by an
      independent patterning mechanism.
AB  - Nerves and vessels often run parallel to one another, a phenomenon that reflects
      their functional interdependency. Previous studies have suggested that
      neurovascular congruency in planar tissues such as skin is established through a
      "one-patterns-the-other" model, in which either the nervous system or the
      vascular system precedes developmentally and then instructs the other system to
      form using its established architecture as a template. Here, we find that, in
      tissues with complex three-dimensional structures such as the mouse whisker
      system, neurovascular congruency does not follow the previous model but rather is
      established via a mechanism in which nerves and vessels are patterned
      independently. Given the diversity of neurovascular structures in different
      tissues, guidance signals emanating from a central organizer in the specific
      target tissue may act as an important mechanism to establish neurovascular
      congruency patterns that facilitate unique target tissue function. 

PMID- 24139046
TI  - Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia.
AB  - The cognitive symptoms of schizophrenia presumably result from impairments of
      information processing in neural circuits. We recorded neural activity in the
      hippocampus of freely behaving mice that had a forebrain-specific knockout of the
      synaptic plasticity-mediating phosphatase calcineurin and were previously shown
      to exhibit behavioral and cognitive abnormalities, recapitulating the symptoms of
      schizophrenia. Calcineurin knockout (KO) mice exhibited a 2.5-fold increase in
      the abundance of sharp-wave ripple (SWR) events during awake resting periods and
      single units in KO were overactive during SWR events. Pairwise measures of unit
      activity, however, revealed that the sequential reactivation of place cells
      during SWR events was completely abolished in KO. Since this relationship during
      postexperience awake rest periods has been implicated in learning, working
      memory, and subsequent memory consolidation, our findings provide a mechanism
      underlying impaired information processing that may contribute to the cognitive
      impairments in schizophrenia. 

PMID- 24139047
TI  - Neural estimates of imagined outcomes in the orbitofrontal cortex drive behavior
      and learning.
AB  - Imagination, defined as the ability to interpret reality in ways that diverge
      from past experience, is fundamental to adaptive behavior. This can be seen at a
      simple level in our capacity to predict novel outcomes in new situations. The
      ability to anticipate outcomes never before received can also influence learning
      if those imagined outcomes are not received. The orbitofrontal cortex is a key
      candidate for where the process of imagining likely outcomes occurs; however, its
      precise role in generating these estimates and applying them to learning remain
      open questions. Here we address these questions by showing that single-unit
      activity in the orbitofrontal cortex reflects novel outcome estimates. The
      strength of these neural correlates predicted both behavior and learning,
      learning that was abolished by temporally specific inhibition of orbitofrontal
      neurons. These results are consistent with the proposal that the orbitofrontal
      cortex is critical for integrating information to imagine future outcomes.

PMID- 24139048
TI  - Hierarchical prediction errors in midbrain and basal forebrain during sensory
      learning.
AB  - In Bayesian brain theories, hierarchically related prediction errors (PEs) play a
      central role for predicting sensory inputs and inferring their underlying causes,
      e.g., the probabilistic structure of the environment and its volatility. Notably,
      PEs at different hierarchical levels may be encoded by different neuromodulatory
      transmitters. Here, we tested this possibility in computational fMRI studies of
      audio-visual learning. Using a hierarchical Bayesian model, we found that low
      level PEs about visual stimulus outcome were reflected by widespread activity in
      visual and supramodal areas but also in the midbrain. In contrast, high-level PEs
      about stimulus probabilities were encoded by the basal forebrain. These findings
      were replicated in two groups of healthy volunteers. While our fMRI measures do
      not reveal the exact neuron types activated in midbrain and basal forebrain, they
      suggest a dichotomy between neuromodulatory systems, linking dopamine to low
      level PEs about stimulus outcome and acetylcholine to more abstract PEs about
      stimulus probabilities.

PMID- 24139049
TI  - SnapShot: Organizational principles of the postsynaptic proteome.

PMID- 24139050
TI  - SnapShot: Auditory transduction.

PMID- 24139051
TI  - Persistence of warfarin therapy for residents in long-term care who have atrial
      fibrillation.
AB  - BACKGROUND: Among long-term care (LTC) residents with atrial fibrillation (AF),
      the use of warfarin to prevent stroke has been shown to be suboptimal. For those
      who begin warfarin prophylaxis in LTC, persistence on this therapy has not been
      reported. OBJECTIVE: This study was conducted to estimate persistence on warfarin
      among LTC residents with AF. METHODS: A retrospective analysis was conducted by
      using data from an LTC database. Pharmacy dispensing data were used to track
      warfarin use in residents with a diagnosis of AF who were newly started on
      warfarin therapy. The main outcome measure was persistence of warfarin over the
      first year of therapy. Survival analysis included Kaplan-Meier plots and a
      multivariate Cox proportional hazards model to test the association of resident
      characteristics and conditions with warfarin discontinuation. RESULTS: A total of
      148 residents new to warfarin therapy met all study inclusion criteria. Median
      age was 84 years; 69% were female. Median time to therapy discontinuation was 197
      days (95% CI, 137-249) across all study residents. By 90 days after the
      initiation of therapy, 37% (95% CI, 28-47) of study residents had discontinued
      warfarin; by 1 year, 65% (54%-76%) had discontinued warfarin therapy. The
      multivariate Cox regression analysis found that the following factors were
      independently associated with discontinuation of warfarin therapy: age 65 to 74
      years (hazard ratio [HR] = 3.01 [95% CI, 1.04-8.73]), female sex (HR = 0.45 [95%
      CI, 0.24-0.87]), Hispanic race/ethnicity (HR = 2.86 [95% CI, 1.30-6.26]), Midwest
      region (HR = 2.13 [95% CI, 1.02-4.48]), and Alzheimer disease or dementia (HR =
      1.97 [95% CI, 1.05-3.68]). CONCLUSIONS: Although clinical practice guidelines
      exist for the prevention of stroke in AF patients, persistence on warfarin
      therapy seems suboptimal in many LTC residents with AF.

PMID- 24139052
TI  - The pathogenesis of retinal and subdural haemorrhage in non-accidental head
      injury in infancy: assessment using Bradford Hill criteria.
AB  - Fatal non-accidental head injury (NAHI) in infancy is characterised by severe
      bilateral retinal haemorrhage (sbRH), thin film diffuse bilateral subdural
      haemorrhage (dbSDH) and severe fatal hypoxic ischaemic encephalopathy (sfHIE).
      The Geddes hypothesis is that sfHIE is the direct cause of sbRH and dbSDH. The
      conventional hypothesis (post-Geddes) is that trauma precipitates hypoxia to
      cause sfHIE and independently tears veins to cause sbRH and dbSDH. These
      hypotheses are assessed using Bradford Hill criteria of causation. The triad
      (sbRH, dbSDH and sfHIE) is a strong, specific and consistent association which
      suggests a causative link. Furthermore sbRH and dbSDH are positively correlated
      with severity of HIE but negatively correlated with objective evidence of trauma.
      The conventional hypothesis (post-Geddes) fails the test of biological
      plausibility because trauma causes asymmetrical and focal bleeding not diffuse
      bilateral capillary and venular oozing. The conventional hypothesis lacks
      coherence since it was shown that the encephalopathy of the triad is not
      traumatic. Arguments by analogy also support the Geddes hypothesis. There is a
      paucity of experimental evidence for either hypothesis but this is likely to be
      rectified as molecular methods (genomics and proteomics) are used in the infant
      autopsy. 

PMID- 24139053
TI  - Impact of abdominal obesity and ambulatory blood pressure in the diagnosis of
      left ventricular hypertrophy in never treated hypertensives.
AB  - BACKGROUND AND OBJECTIVES: The principal objective was to assess the prevalence
      of left ventricular hypertrophy (LVH) in hypertensive, never treated patients,
      depending on adjustment for body surface or height. Secondary objectives were to
      determine geometric alterations of the left ventricle and to analyze the
      interdependence of hypertension and obesity to induce LVH. PATIENTS AND METHODS:
      Cross-sectional study that included 750 patients (387 men) aged 47 (13, SD) years
      who underwent ambulatory blood pressure (ABPM) monitoring and echocardiography.
      RESULTS: The prevalence of LVH was 40.4% (303 patients), adjusted for body
      surface area (BSA, LVHBSA), and 61.7% (463 patients), adjusted for height(2.7)
      (LVHheight(2.7)). In a multivariate logistic analysis, systolic BP24h, gender and
      presence of elevated microalbuminuria were associated with both LVHBSA and
      LVHheight(2.7). Increased waist circumference was the strongest independent
      predictor of LVHheight(2.7), but was not associated with LVHBSA. We found a
      significant interaction between abdominal obesity and systolic BP24h in
      LVHheight(2.7). Concentric remodelling seems to be the most prevalent alteration
      of left ventricular geometry in early stages of hypertension (37.5%).
      CONCLUSIONS: The impact of obesity as predictor of LVH in never treated
      hypertensives is present only when left ventricular mass (LVM) is indexed to
      height(2.7). Obesity interacts with systolic BP24h in an additive but not merely
      synergistic manner. Systolic BP24h is the strongest determinant of LVH when
      indexed for BSA.

PMID- 24139054
TI  - Left atrial volumes and associated stroke subtypes.
AB  - BACKGROUND: Cardio embolism and cerebrovascular atherosclerosis are two major
      mechanisms of stroke. Studies investigating associations between advanced
      echocardiographic parameters and stroke mechanisms are limited. METHODS: This
      study is a standardized review of 633 patients admitted to the stroke service of
      a tertiary care hospital following a standardized stroke investigation and
      management pathway. Stroke subtypes were characterized using the Causative
      Classification System, using the hospitals online radiologic archival system with
      CCS certified stroke investigators. Patients with two mechanisms were excluded.
      RESULTS: Patients with cardioembolic stroke had a higher proportion of atrial
      fibrillation (p < 0.001), acute myocardial infarction (p < 0.001) and ischemic
      heart disease (p < 0.001). On electrocardiogram (ECG) and transthoracic Echo
      (TTE), patients with cardioembolic stroke had a greater atrial fibrillation (p <
      .00), left ventricular thrombus (p < .00), left ventricular ejection fraction
      <30% (p < .00) and global hypokinesia (p < .00) Patients with cardioembolic
      stroke had higher mean left atrial volume indices (LAVi) (p < 0.001), mean left
      ventricular mass indices (LVMi) (p < 0.05) and mean left atrial diameters (LAD)
      (p < 0.05). At LAVi of 29-33 ml/m2, the risk of atherothrombotic stroke
      increased. The risk of cardioembolic stroke increased with LAVi of 34 ml/m2 and
      above. CONCLUSION: Left atrial volume indices may be linked to specific stroke
      phenotype. At mild increases in left atrial dimensions, the risks of
      atherosclerotic stroke are high, and probably reflect hypertension as the
      unifying mechanism. Further increases in left atrial dimensions shifts the risk
      towards cardioembolic stroke.

PMID- 24139055
TI  - Frequency of child maltreatment in a representative sample of the German
      population.
AB  - BACKGROUND: Representative data about the frequency of child maltreatment is
      needed in order to estimate the extent of the problem in the wider population as
      well as to provide the basis for interpretation of frequency rates in clinical
      samples. However, previous representative studies on the frequency of child
      maltreatment in Germany and other countries were limited as they focused on the
      assessment of physical and sexual abuse whilst emotional forms of maltreatment
      were ignored. In addition, previous studies applied scales that had not been
      validated against external criteria. METHODS: In a cross-sectional study,
      standardized questionnaires were administered to a representative sample of the
      German population. Maltreatment in childhood and adolescence was assessed using
      the German version of the Childhood Trauma Questionnaire. Empirically derived
      threshold values for the five different types of child maltreatment including
      emotional maltreatment were applied to determine presence of abuse and neglect.
      RESULTS: Complete data was available from N = 2,500 subjects. Prevalence rates
      were 13.9% for emotional neglect, 10.2% for emotional abuse, 12.0% for physical
      abuse, 48.4% for physical neglect, and 6.2% for sexual abuse. Differences between
      sexes were found for the frequency of sexual abuse. CONCLUSIONS: Although our
      analysis has found lower rates of child maltreatment than previous reports that
      used less well validated criteria, the results of this study confirm that child
      abuse, with its many different facets, is a significant problem in Germany.

PMID- 24139056
TI  - Elevated left ventricular outflow tract velocities on exercise stress
      echocardiography may be a normal physiologic response in healthy youth.
AB  - BACKGROUND: Children with heart disease are at risk for sudden death during
      exercise, yet decisions regarding sports participation are often based on resting
      data. Acceleration across the left ventricular outflow tract (LVOT) assessed on
      stress echocardiography may suggest a diagnosis of hypertrophic cardiomyopathy in
      patients in whom it is not otherwise obvious. However, the range of peak
      velocities across the LVOT in healthy youth is unknown. The aim of this study was
      to describe LVOT velocities with maximal exercise in this age group. METHODS:
      Subjects up to 18 years old were prospectively enrolled if they had normal
      results on resting echocardiography and were undergoing exercise testing for
      other reasons. Subjects with significant comorbidities, suspected cardiomyopathy,
      or family histories of cardiomyopathy were excluded. Peak LVOT velocities were
      measured in the upright position using continuous-wave Doppler immediately after
      maximal exercise. RESULTS: Fifty subjects (mean age, 13.8 +/- 2.8 years) were
      included. Twenty-eight (56%) were male, and 40 (80%) were Caucasian. The median
      peak LVOT velocity measured immediately after exercise was 2.5 m/sec (range, 1.3
      5.9 m/sec). Sixteen subjects (32%) developed peak LVOT velocities of >=3 m/sec.
      Twelve of the 16 (75%) with elevated velocities had a dynamic outflow tract
      Doppler pattern, of whom eight had evidence of intracavitary narrowing on two
      dimensional echocardiography. CONCLUSIONS: The development of significant
      exercise-induced LVOT velocities may be a normal physiologic finding in healthy
      youth. The measurement of LVOT velocities alone with maximal exercise may not
      help distinguish patients with hypertrophic cardiomyopathy from healthy children.

PMID- 24139057
TI  - Person-centred web-based support--development through a Swedish multi-case study.
AB  - BACKGROUND: Departing from the widespread use of the internet in modern society
      and the emerging use of web applications in healthcare this project captures
      persons' needs and expectations in order to develop highly usable web recourses.
      The purpose of this paper is to outline a multi-case research project focused on
      the development and evaluation of person-centred web-based support for people
      with long-term illness. To support the underlying idea to move beyond the
      illness, we approach the development of web support from the perspective of the
      emergent area of person-centred care. The project aims to contribute to the
      ongoing development of web-based supports in health care and to the emerging
      field of person-centred care. METHODS/DESIGN: The research design uses a meta
      analytical approach through its focus on synthesizing experiences from four
      Swedish regional and national cases of design and use of web-based support in
      long-term illness. The cases include children (bladder dysfunction and urogenital
      malformation), young adults (living close to persons with mental illness), and
      two different cases of adults (women with breast cancer and childbearing women
      with type 1 diabetes). All of the cases are ongoing, though in different stages
      of design, implementation, and analysis. This, we argue, will lead to a synthesis
      of results on a meta-level not yet described. DISCUSSION: To allow valid
      comparisons between the four cases we explore and problematize them in relation
      to four main aspects: 1) The use of people's experiences and needs; 2) The role
      of use of theories in the design of person-centred web-based supports; 3) The
      evaluation of the effects of health outcomes for the informants involved and 4)
      The development of a generic person-centred model for learning and social support
      for people with long-term illness and their significant others. Person-centred
      web-based support is a new area and few studies focus on how web-based
      interventions can contribute to the development of person-centred care. In
      summary, the main intention of the project outlined here is to contribute with
      both a synthesis of results on meta-level from four cases and a substantial
      contribution to the field person-centred care.

PMID- 24139058
TI  - Delirium in palliative care: Detection, documentation and management in three
      settings.
AB  - OBJECTIVES: Delirium is characterized by disturbances of consciousness and
      changes in cognition that develop rapidly and fluctuate. It is common in
      palliative care, affecting up to 88% of patients with advanced cancer, yet often
      remains insufficiently diagnosed and managed. This study sought to compare rates
      of screening, documentation, and management of delirium across three palliative
      care settings - two hospices and one hospital team - and to determine whether
      definitive documentation of delirium as a diagnosis is associated with improved
      management of the disorder. METHODS: A retrospective review of patient case notes
      was performed in three U.K. palliative care settings for the presence of:
      cognitive screening tools on first assessment; the term "delirium" as a stated
      documented diagnosis; documented terms, descriptions, and synonyms suggestive of
      delirium; and management plans aimed at addressing delirium. RESULTS: We reviewed
      319 notes. The prevalence of delirium as a documented diagnosis ranged from 0 to
      8.4%, rising to 35.7-39.2% when both documented delirium and descriptions
      suggestive of delirium were taken into account. An abbreviated mental test score
      (AMTS) was determined for 19.6 (H1) and 26.8% (H2) of hospice admissions and for
      0% of hospital assessments. Symptoms suggestive of delirium were managed in 56.3%
      of cases in hospital, compared with 66.7 (H1) and 72.2% (H2) in hospices.
      SIGNIFICANCE OF RESULTS: Use of the term "delirium" was infrequent in both
      hospital and hospice palliative care settings, as was the use of routine
      screening. Many identified cases did not receive targeted management. The
      definitive use of the term as a diagnosis was associated with clearer management
      plans in hospital patients. The authors suggest that better screening and
      identification remains the first step in improving delirium management.

PMID- 24139059
TI  - Nanotetrapods: quantum dot hybrid for bulk heterojunction solar cells.
AB  - Hybrid thin film solar cell based on all-inorganic nanoparticles is a new member
      in the family of photovoltaic devices. In this work, a novel and performance
      efficient inorganic hybrid nanostructure with continuous charge transportation
      and collection channels is demonstrated by introducing CdTe nanotetropods (NTs)
      and CdSe quantum dots (QDs). Hybrid morphology is characterized, demonstrating an
      interpenetration and compacted contact of NTs and QDs. Electrical measurements
      show enhanced charge transfer at the hybrid bulk heterojunction interface of NTs
      and QDs after ligand exchange which accordingly improves the performance of solar
      cells. Photovoltaic and light response tests exhibit a combined optic-electric
      contribution from both CdTe NTs and CdSe QDs through a formation of
      interpercolation in morphology as well as a type II energy level distribution.
      The NT and QD hybrid bulk heterojunction is applicable and promising in other
      highly efficient photovoltaic materials such as PbS QDs. 

PMID- 24139060
TI  - Take 'em or leave 'em: management of the ovaries in young women with endometrial
      cancer.

PMID- 24139061
TI  - An exploratory study of ambient air toxics exposure in pregnancy and the risk of
      neuroblastoma in offspring.
AB  - Little is known about the etiology of neuroblastoma, the most common cancer in
      infancy. In this study, we examined maternal exposure to ambient air toxics in
      pregnancy in relation to neuroblastoma in the child. We ascertained all cases of
      neuroblastoma listed in the California Cancer Registry 1990-2007 that could be
      linked to a California birth certificate, and controls were selected at random
      from California birth records. Average air toxics exposures during pregnancy were
      determined based upon measures from community-based air pollution monitors. The
      study included 75 cases and 14,602 controls who lived with 5 km of an air
      pollution monitor, and we additionally examined results for those living within a
      smaller radius around the monitor (2.5 km). Logistic regression was used to
      determine the risk of neuroblastoma with one interquartile range increase in air
      toxic exposure. Neuroblastoma risk was increased with higher maternal exposure to
      carbon tetrachloride (OR=2.65, 95%CI 1.07, 6.53) and polycyclic aromatic
      hydrocarbons (OR=1.39, 95%CI 1.05, 1.84), particularly indeno(1,2,3-cd)pyrene and
      dibenz(a,h)anthracene. Hexavalent chromium was associated with neuroblastoma at
      the 5 km distance (OR=1.32, 95%CI 1.00, 1.74) but not at the 2.5 km distance.
      This is one of the first studies to report associations between neuroblastoma and
      these air toxics.

PMID- 24139062
TI  - The Drosophila anatomy ontology.
AB  - BACKGROUND: Anatomy ontologies are query-able classifications of anatomical
      structures. They provide a widely-used means for standardising the annotation of
      phenotypes and expression in both human-readable and programmatically accessible
      forms. They are also frequently used to group annotations in biologically
      meaningful ways. Accurate annotation requires clear textual definitions for
      terms, ideally accompanied by images. Accurate grouping and fruitful programmatic
      usage requires high-quality formal definitions that can be used to automate
      classification and check for errors. The Drosophila anatomy ontology (DAO)
      consists of over 8000 classes with broad coverage of Drosophila anatomy. It has
      been used extensively for annotation by a range of resources, but until recently
      it was poorly formalised and had few textual definitions. RESULTS: We have
      transformed the DAO into an ontology rich in formal and textual definitions in
      which the majority of classifications are automated and extensive error checking
      ensures quality. Here we present an overview of the content of the DAO, the
      patterns used in its formalisation, and the various uses it has been put to.
      CONCLUSIONS: As a result of the work described here, the DAO provides a high
      quality, queryable reference for the wild-type anatomy of Drosophila melanogaster
      and a set of terms to annotate data related to that anatomy. Extensive, well
      referenced textual definitions make it both a reliable and useful reference and
      ensure accurate use in annotation. Wide use of formal axioms allows a large
      proportion of classification to be automated and the use of consistency checking
      to eliminate errors. This increased formalisation has resulted in significant
      improvements to the completeness and accuracy of classification. The broad use of
      both formal and informal definitions make further development of the ontology
      sustainable and scalable. The patterns of formalisation used in the DAO are
      likely to be useful to developers of other anatomy ontologies.

PMID- 24139063
TI  - Exploration of specialty certification for nurse anesthetists: nonsurgical pain
      management as a test case.
AB  - Certification is the outcome of the demonstration of knowledge and skills, which
      is an important link to licensing and credentialing. Considering the essential
      role that Certified Registered Nurse Anesthetists play in the practice of
      nonsurgical pain management, it is important that a certification process be
      developed that provides the necessary support to licensing and credentialing at
      the local, state, and federal levels. The goal of this project was to develop the
      foundational elements for a specialty certification in nonsurgical pain
      management. The Delphi method for the systematic solicitation and collation of
      information was used to query experts in the field of nonsurgical pain management
      regarding the elements necessary to establish such a specialty certification.
      Results of the query were compiled, analyzed, and compared to feedback about the
      elements from a sample of certified registered nurse anesthetists involved in
      nonsurgical pain management to assess reliability. The results provided
      identification of a target population for competency evaluation, tools for
      evaluation, resources for knowledge and skills testing, and a table of
      specifications for testing. A valid process to develop a specialty certification
      for nurse anesthetists with demonstration of knowledge and skills will help
      bridge the gap between continuing education and an actual demonstration that an
      individual practitioner possesses the necessary knowledge and skills to practice
      nonsurgical pain management. 

PMID- 24139064
TI  - Characterization of acetylcholinesterase inhibition and energy allocation in
      Daphnia magna exposed to carbaryl.
AB  - The inhibition of acetylcholinesterase (AChE) activity and energy allocation in
      the freshwater organism Daphnia magna exposed to carbaryl and potential recovery
      from the effects was examined. The binding of carbaryl-AChE was characterized
      through in vitro assays. To evaluate the recovery from inhibition and the
      alteration in energy budget, in vivo exposure and recovery regime tests were
      conducted. In comparison to diazoxon, the active metabolite of the insecticide
      diazinon, the stability of enzyme-carbaryl complex was fifteen times lower and
      the reactivity toward the active site was two times lower, resulting in
      approximately 30 times lower overall inhibition rate than for diazoxon. The in
      vitro reactivation rate constant of the inhibited enzyme and the in vivo recovery
      rate constant of AChE activity were 1.9 h-1 and 0.12 h-1 for carbaryl,
      respectively, which are much higher than the corresponding rate constants for
      diazoxon. The lower AChE inhibition and greater reactivation/recovery rates are
      in accordance with the lower toxicity of carbaryl compared to diazinon. Carbaryl
      exposure also altered the profile of the energy reserve: the decrease in lipid
      and glycogen and the increase in protein content resulted in the reduction of the
      total energy budget by about 45 mJ/g(ww). This corresponds to 26 percent of the
      available energy, which might allocate for external stressors. The mechanistic
      model of AChE inhibition is helpful to get an insight into (eco-)toxicological
      effects of AChE inhibitors on freshwater crustaceans under environmentally
      realistic conditions.

PMID- 24139065
TI  - Cathepsin B as a potential prognostic and therapeutic marker for human lung
      squamous cell carcinoma.
AB  - BACKGROUND: The lung squamous cell carcinoma survival rate is very poor despite
      multimodal treatment. It is urgent to discover novel candidate biomarkers for
      prognostic assessment and therapeutic targets to lung squamous cell carcinoma
      (SCC). RESULTS: Herein a two-dimensional gel electrophoresis and ESI-Q-TOF MS/MS
      based proteomic approach was used to identify differentially expressed proteins
      between lung SCC and adjacent normal tissues. 31 proteins with significant
      alteration were identified. These proteins were mainly involved in metabolism,
      calcium ion binding, signal transduction and so on. Cathepsin B (CTSB) was one of
      the most significantly altered proteins and was confirmed by western blotting.
      Immunohistochemistry showed the correlation between higher CTSB expression and
      lower survival rate. No statistically significant difference between CTSB-shRNA
      treated group and the controls was observed in tumor volume, tumor weight,
      proliferation and apoptosis. However, the CTSB-shRNA significantly inhibited
      tumor metastases and prolonged survival in LL/2 metastatic model. Moreover, CTSB,
      Shh and Ptch were up-regulated in patients with metastatic lung SCC, suggesting
      that hedgehog signaling might be activated in metastatic lung SCC which could
      affect the expression of CTSB that influence the invasive activity of lung SCC.
      CONCLUSIONS: These data suggested that CTSB might serve as a prognostic and
      therapeutic marker for lung SCC.

PMID- 24139066
TI  - Choosing between Internet-based psychodynamic versus cognitive behavioral therapy
      for depression: a pilot preference study.
AB  - BACKGROUND: Major depression is a world-wide problem that can be treated with
      various forms of psychotherapy. There is strong research support for treating
      major depression using cognitive behavior therapy delivered in the format of
      guided self-help via the Internet (ICBT). Recent research also suggests that
      psychodynamic psychotherapy can be delivered as guided self-help via the Internet
      (IPDT) and that it seem to be as effective as ICBT for mild to moderate
      depression. However, no head-to-head comparison between the two treatments
      exists. In the field of Internet interventions it is largely unexplored if
      treatment preference affects outcome and adherence. METHODS: Participants were
      allocated to IPDT or ICBT based on their stated preference. More than half of the
      participants preferred ICBT (N = 30) over IPDT (N = 14). Differences in efficacy
      between treatments were explored. Correlations between strength of preference and
      treatment outcome, adherence to treatment and completion of the whole treatment
      program were explored. Data were collected before and after treatment, as well as
      in a 7-month follow-up. RESULTS: During the treatment period, both programs
      performed equally well in reducing symptoms. More participants who received IPDT
      completed the entire program. At follow-up, mixed-effects models showed that
      participants who chose ICBT improved more in terms of quality of life. The ICBT
      group also had a significant increase in participants who recovered from their
      depression from post-treatment to follow-up. Exploratory analyses indicated that
      strength of preference was correlated with adherence to treatment and completion
      of the whole program, and long-term outcome for the ICBT group. CONCLUSIONS: Few
      differences were found during the acute treatment phase, but the long-term
      effects are in favor of ICBT. Strength of preference for treatment seems to have
      a predictive value. Further research comparing the efficacy of ICBT and IPDT, and
      the effects of preference matching and strength of preference, is warranted.
      TRIAL REGISTRATION: This trial is a continuation of the study registered as
      NCT01324050 at Clinicaltrials.gov.

PMID- 24139067
TI  - Safety and efficacy of mitoxantrone in pediatric patients with aggressive
      multiple sclerosis.
AB  - OBJECTIVE: The purpose of this study was to assess the safety and efficacy of
      mitoxantrone (MX) in pediatric patients with aggressive multiple sclerosis (MS).
      METHODS: A retrospective analysis on pediatric MS patients treated with MX was
      performed with regards to demographic/clinical parameters and magnetic resonance
      imaging (MRI) findings. RESULTS: 19 definite pediatric MS cases with mean +/- SD
      age of 15.4 +/- 2.8 years underwent 20 mg MX for control of their severe/frequent
      relapses, high EDSS score or new and active brain MRI lesions. After a median
      [IQR] follow-up period of 30[12-60] months, 14 cases (73%) were relapse free; the
      EDSS score decreased by at least 0.5 in 16 cases (84.2%); and gadolinium
      enhancing lesion volume fell by 84.2% in 16 cases. Adverse events included nausea
      and vomiting, fatigue, alopecia, palpitation, cardiomyopathy and mild leukopenia.
      All adverse events were mild and transient. CONCLUSION: Our results suggest MX is
      a good candidate for treatment of children with worsening RRMS and SPMS.
      Recommendations regarding patient selection, treatment administration, and close
      follow-up should be considered. Continuing research is needed to establish its
      efficacy and safety profile in a multinational collaboration with careful follow
      up of adverse events.

PMID- 24139068
TI  - Breast cancer arising at a young age: do we need to define a cut-off?

PMID- 24139069
TI  - Synchronous and metachronous metastatic breast cancer--two incarnations of the
      same beast?

PMID- 24139070
TI  - Method to grow Actinobacillus pleuropneumoniae biofilm on a biotic surface.
AB  - BACKGROUND: Actinobacillus pleuropneumoniae is a Gram-negative bacterium and a
      member of the Pasteurellaceae family. This bacterium is the causative agent of
      porcine pleuropneumonia, which is a highly contagious respiratory disease causing
      important economical losses to the worldwide pig industry. It has been shown that
      A. pleuropneumoniae can form biofilms on abiotic surfaces (plastic and glass).
      Although in vitro models are extremely useful to gain information on biofilm
      formation, these models may not be representative of the conditions found at the
      mucosal surface of the host, which is the natural niche of A. pleuropneumoniae.
      RESULTS: In this paper, we describe a method to grow A. pleuropneumoniae biofilms
      on the SJPL cell line, which represents a biotic surface. A non-hemolytic, non
      cytotoxic mutant of A. pleuropneumoniae was used in our assays and this allowed
      the SJPL cell monolayers to be exposed to A. pleuropneumoniae for longer periods.
      This resulted in the formation of biofilms on the cell monolayer after
      incubations of 24 and 48 h. The biofilms can be stained with fluorescent probes,
      such as a lectin against the polymer of N-acetyl-D-glucosamine present in the
      biofilm matrix, and easily observed by confocal laser scanning microscopy.
      CONCLUSIONS: This is the first protocol that describes the formation of an A.
      pleuropneumoniae biofilm on a biotic surface. The advantage of this protocol is
      that it can be used to study biofilm formation in a context of host-pathogen
      interactions. The protocol could also be adapted to evaluate biofilm inhibitors
      or the efficacy of antibiotics in the presence of biofilms.

PMID- 24139071
TI  - Unrecognized bilateral temporomandibular joint dislocation after general
      anesthesia with a delay in diagnosis and management: a case report.
AB  - INTRODUCTION: Anterior bilateral temporomandibular joint dislocation is not an
      uncommon occurrence and has been reported before. However, its diagnosis can
      easily be overlooked, especially by clinicians who are unfamiliar with this
      pathology. Continuous discussion of the pathology is required to prevent delays
      in diagnosis, which can lead to long-term sequelae for the patient. CASE
      PRESENTATION: We present the case of a 66-year-old Somali woman who experienced a
      bilateral anterior temporomandibular joint dislocation after a general anesthetic
      for an exploratory laparotomy for excision of a pelvic sarcoma. She first
      presented in the intensive care unit with preauricular pain and an inability to
      close her mouth, and was initially misdiagnosed and treated for a muscle spasm.
      The cause of her misdiagnosis was multifactorial - opioid-related sedation,
      language and cultural barrier, and unfamiliarity with the pathology. Her
      diagnosis was proven 18 hours after the completion of surgery with a plain X-ray.
      A manual closed reduction was performed with minimal sedation by oral surgery.
      CONCLUSION: We provided an in-depth discussion of temporomandibular joint
      dislocation and suggest a simple test that would prevent delayed diagnosis of
      temporomandibular joint dislocation in any patient undergoing general anesthesia.
      A normal mandibular excursion should be tested in every patient after surgery in
      the postoperative care unit, by asking the patient to open and close their mouth
      during the immediate postoperative recovery period or passively performing the
      range of motion test.

PMID- 24139072
TI  - Pleomorphic adenoma of the nasal septum.
AB  - INTRODUCTION: Pleomorphic adenoma is the most common benign tumour of the
      salivary glands. The major salivary glands are most commonly involved, or more
      rarely accessory salivary glands, especially the oral cavity. Other locations,
      such as the nasal cavity, paranasal sinuses or upper aerodigestive tract, are
      exceptional. CASE REPORT: A 26-year-old female presented with right-sided nasal
      obstruction. Radiology found a lesion involving the anterior third of the nasal
      septum. The patient underwent complete surgical resection of the tumour via an
      endonasal approach. Histological examination found a mixed cellular component
      (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid
      stroma, enabling diagnosis of a typical pleomorphic adenoma.
      DISCUSSION/CONCLUSION: Pleomorphic adenoma is exceptional in the nasal cavity,
      with only a few cases reported in the literature. Although benign, the risk of
      local recurrence, malignant transformation and metastasis requires close long
      term follow-up.

PMID- 24139073
TI  - Partial laryngectomy as salvage surgery after radiotherapy: oncological and
      functional outcomes and impact on quality of life. A retrospective study of 20
      cases.
AB  - The gold standard for the management of laryngeal squamous cell carcinoma in a
      previously irradiated patient is "salvage" total laryngectomy, but surgical
      management by partial laryngectomy can sometimes be proposed in selected
      patients. OBJECTIVES: This study was designed to review the functional and
      oncological outcomes of patients treated by open partial laryngectomy for
      recurrent squamous cell carcinoma after failure of radiotherapy or involving
      previously irradiated tissues and to define prognostic criteria for the selection
      of patients eligible for this treatment strategy. MATERIALS AND METHODS: In this
      retrospective study, 20 patients underwent partial laryngectomy between 2000 and
      2011 for recurrence or second primary stage I or II laryngeal squamous cell
      carcinoma in an irradiated territory (11 vertical partial laryngectomies; 9
      horizontal partial laryngectomies). RESULTS: The 3-year overall survival rate in
      patients with negative resection margins was 66%, with higher survival rates for
      tumours confined to the glottis, and the 2-year local control rate was 67%.
      Positive resection margins requiring total laryngectomy were observed in 20% of
      cases. The 3-year overall survival rate was 56% in these patients. Exclusive oral
      feeding was restored in 75% of patients after an average of 32 days. The
      tracheotomy tube was removed after an average of 18 days in 90% of patients. The
      disease-free functional larynx preservation rate was 45%. CONCLUSIONS: Salvage
      partial laryngectomy in irradiated tissues is an alternative treatment option to
      total laryngectomy in selected patients.

PMID- 24139074
TI  - An original submandibular approach technique sparing the cervical branch of the
      facial nerve.
AB  - Many articles and anatomy textbooks accurately describe the anatomy and
      anatomical variations of the marginal mandibular branch of the facial nerve
      (VII). This is not, however, true for the cervical branch, damage to which
      results in paralysis of the platysma and, because of its insertions at the lower
      lip and labial commissure, in disfigurement, especially when smiling. This may be
      mistaken for paralysis of the marginal mandibular branch of the facial nerve.
      Precise anatomical description of the cervical branch of the facial nerve allows
      certain technical safeguards to be determined which, if adhered to, should reduce
      the risk of injury, especially during surgical excision of the submandibular
      gland on a transcervical approach. 

PMID- 24139075
TI  - Ossifying fibroma of the middle turbinate revealed by infection in a young child.
AB  - INTRODUCTION: Ossifying fibroma (OF) is a rare benign fibro-osseous tumor, mainly
      located in the head and neck region. Most often, it affects the mandible but rare
      involvement of paranasal sinuses has been reported, associated with more locally
      aggressive behavior. CASE REPORT: We report the case of an 8-year-old boy with OF
      of the middle turbinate, revealed by ethmoiditis. Total resection was performed
      on an endoscopic approach. The patient was free of clinical or radiological
      recurrence at 3 years' follow-up. This was the youngest patient with OF of the
      middle turbinate so far reported in the international literature. DISCUSSION:
      Presumptive diagnosis is established by clinical examination and CT scan
      (location, oval-shaped mass, heterogeneous tumor with a thin bony rim).
      Definitive diagnosis is founded on histological examination (psammomatous bodies,
      osteoblastic rim, trabecular bone). Treatment in paranasal sinus OF is surgical,
      preferentially on an endoscopic approach. Resection should be as complete as
      possible to minimize risk of recurrence, especially in sinonasal locations, known
      to be more aggressive. Ethmoiditis in an unusual age-range should suggest tumoral
      etiology.

PMID- 24139077
TI  - Quality of life and toxicity from passively scattered and spot-scanning proton
      beam therapy for localized prostate cancer.
AB  - PURPOSE: To report quality of life (QOL)/toxicity in men treated with proton beam
      therapy for localized prostate cancer and to compare outcomes between passively
      scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). METHODS
      AND MATERIALS: Men with localized prostate cancer enrolled on a prospective QOL
      protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups
      were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate
      Cancer Index Composite questionnaires at baseline and every 3-6 months after
      proton beam therapy. Clinically meaningful differences in QOL were defined as
      >=0.5 * baseline standard deviation. The cumulative incidence of modified
      Radiation Therapy Oncology Group grade >=2 gastrointestinal (GI) or genitourinary
      (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier
      method. RESULTS: A total of 226 men received PSPT, and 65 received SSPT. Both
      PSPT and SSPT resulted in statistically significant changes in sexual, urinary,
      and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel
      summary, function, and bother resulted in clinically meaningful decrements beyond
      treatment completion. The decrement in bowel QOL persisted through 24-month
      follow-up. Cumulative grade >=2 GU and GI toxicity at 24 months were 13.4% and
      9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other
      grade >=3 GI or GU toxicity. Argon plasma coagulation application was infrequent
      (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were
      appreciated between PSPT and SSPT regarding toxicity or QOL. CONCLUSION: Both
      PSPT and SSPT confer low rates of grade >=2 GI or GU toxicity, with preservation
      of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically
      meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or
      QOL differences between PSPT and SSPT were identified. Long-term comparative
      results in a larger patient cohort are warranted.

PMID- 24139078
TI  - Mental disorder and criminality in Canada.
AB  - This article examines the relationship between mental disorder and criminality in
      Canada from the colonial period to the landmark 1992 Mental Disorder Amendments
      that followed the passing of Bill C-30. The history of this relationship has been
      shaped by longstanding formal and informal systems of social regulation, by the
      contests of federal-provincial jurisdiction, by changing trends in the legal and
      psychiatric professions, and by amendments to the federal Criminal Code. A study
      of these longer-term features demonstrates that there has been no linear path of
      progress in Canada's response to mentally unwell offenders. Those caught in the
      web of crime and mental disorder have been cast and recast over the past 150
      years by the changing dynamics of criminal law, psychiatry, and politics. A long
      historical perspective suggests how earlier and more contemporary struggles over
      mental disorder and criminality are connected, how these struggles are bound by
      historical circumstance, and how a few relatively progressive historical moments
      emerging from these struggles might be recovered, and theorized to advantage.

PMID- 24139079
TI  - Endoscopic therapy in inflammatory bowel diseases (with videos).
AB  - Endoscopic therapies are important modalities in the treatment of IBD, adjunct to
      medical and surgical approaches. These therapeutic techniques are particularly
      useful in the management of IBD-associated or IBD surgery-associated strictures,
      fistulas, and sinuses and colitis-associated neoplasia. Although the main focus
      of endoscopic therapies in IBD has been on balloon stricture dilation and
      ablation of adenoma-like lesions, new endoscopic approaches are emerging,
      including needle-knife stricturotomy, needle-knife sinusotomy, endoscopic stent
      placement, and fistula tract injection. Risk management of endoscopy-associated
      adverse events is also evolving. The application of endoscopic techniques in
      novel ways in the treatment of IBD is just beginning and will likely expand
      rapidly in the near future.

PMID- 24139080
TI  - An update on the management of implanted cardiac devices during electrosurgical
      procedures.
AB  - To date, the major guidelines for the management of implanted cardiac devices
      during electrosurgical procedures have come from 1 of several major medical
      societies.These most recent guidelines are from the ACCF/AHA in 2009, a combined
      consensus statement from the Heart Rhythm Society and the American Society of
      Anesthesiologists in 2011, as well as an update from the ASGE in 2007. Tables 1
      and 2 summarize the most recent recommendations by society. Further studies are
      needed so that data can be available for the specialty societies to unify
      consensus on guidelines on the proper management of patients with implanted
      cardiac devices.

PMID- 24139081
TI  - [Alveolar proteinosis in an immunocompetent patient with previous Legionella and
      Nocardia infections].

PMID- 24139082
TI  - Anal carcinoma and HIV infection: is it time for screening?
AB  - A 38-year-old white man had a 10-year history of human immunodeficiency virus
      (HIV) infection (A3), with no episodes of opportunistic diseases and in good
      immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while
      on HAART. He presented with a two-month history of mild anal symptoms, including
      pruritus and episodic bleeding. He referred past episodes of anal warts, self
      treated with several topical compounds, all proven unsuccessful. Perianal
      examination showed erythema and scratching. A 0.5cm sized tumor, with
      infiltration at the base was detected on digital exam, located at 15mm from the
      anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a
      final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have
      been prevented? 

PMID- 24139083
TI  - Fitz-Hugh-Curtis syndrome in males: Increasing prevalence of a rare clinical
      entity.

PMID- 24139085
TI  - Pharmacodynamic interaction between stiripentol and benzodiazepines: from
      molecular to clinical studies.

PMID- 24139084
TI  - Autoimmune causes of encephalitis syndrome in Thailand: prospective study of 103
      patients.
AB  - BACKGROUND: Data on encephalitis in Thailand have not been completely described.
      Etiologies remain largely unknown. We prospectively analyzed 103 Thai patients
      from 27 provinces for the causes of encephalitis using clinical, microbiological
      and neuroimaging indices; caseswithout a diagnosis were evaluated for autoimmune
      causes of encephalitis. METHODS: Patients with encephalitis and/or myelitis were
      prospectively studied between October 2010 and August 2012. Cases associated with
      bacterial, rickettsial and mycobacterial diseases were excluded. Herpes viruses 1
      6 and enteroviruses infection was diagnosed using PCR evaluation of CSF; dengue
      and JE viruses infection, by serology. The serum of test-negative patients was
      evaluated for the presence of autoantibodies. RESULTS: 103 patients were
      recruited. Fifty-three patients (52%) had no etiologies identified. Twenty-five
      patients (24%) were associated with infections. Immune encephalitis was found in
      25 (24%); neuropsychiatric lupus erythematosus (4), demyelinating diseases (3),
      Behcet's disease (1) and the remaining had antibodies to NMDAR (5), ANNA-2 (6),
      Yo (2), AMPA (1), GABA (1), VGKC (1) and NMDA coexisting with ANNA-2 (1).
      Presenting symptoms in the autoimmune group included behavioral changes in 6/25
      (versus 12/25 in infectious and 13/53 in unknown group) and as psychosis in 6/25
      (versus 0/25 infectious and 2/53 unknown). Seizures were found in 6/25
      autoimmune, 4/25 infectious and 19/53 unknown group. Two patients with anti-ANNA
      2 and one anti-Yo had temporal lobe involvement by magnetic resonance imaging.
      Two immune encephalitis patients with antibodies to NMDAR and ANNA-2 had ovarian
      tumors. CONCLUSIONS: Autoantibody-associated encephalitis should be considered in
      the differential diagnosis and management algorithm regardless of clinical and
      neuroimaging features.

PMID- 24139086
TI  - Determining minimally important change thresholds for the Seizure Severity
      Questionnaire (SSQ).
AB  - The Seizure Severity Questionnaire (SSQ) was developed to evaluate changes in
      seizure severity and bothersomeness. Determination of a threshold value
      reflecting meaningful patient benefit on the SSQ would improve clinical
      interpretation of scale results. The objective of this analysis was to define a
      minimally important change (MIC) threshold for the SSQ, using data from patients
      with treatment-resistant partial-onset seizures from two clinical trials (N=776).
      Minimally important change thresholds were calculated using standard anchor-based
      methods, with the Patient Global Impression of Change (PGIC) score as the anchor
      with the categories of 'much improved,' 'minimally improved,' 'much worsened,'
      and 'minimally worsened' combined. The calculated MIC thresholds (range: 0.34 to
      0.50) suggest that a 0.48-point change in the SSQ total score reflects a
      clinically meaningful change in seizure severity from the patients' perspective. 

PMID- 24139087
TI  - Hypocalcaemia as a prognostic factor of early mortality in moderate and severe
      traumatic brain injury.
AB  - OBJECTIVES: Our main objective was to evaluate whether serum hypocalcaemia on the
      third day [defined as < 2.1 mmol/l (8.5 mg/dl)] is a prognostic factor for early
      mortality after moderate and severe traumatic brain injury (TBI). METHODS: We
      developed an ambispective comparative case control study. We evaluated clinical
      profiles from included patients from January 2005 to July 2009 and we
      prospectively recruited additional patients from August 2009 to July 2011.
      Patients were between 1 and 89 years old and had a Glasgow Coma Scale of 3-12
      points following TBI. RESULTS: We calculated an Odds Ratio of 5.2 (Confidence
      Intervals 95%: 4.48 to 6.032) for hypocalcaemia on day three, which was
      associated with death. Retrospectively (January 2005 to July 2009) we compiled
      data from 81 patients. Prospectively (August 2009 to July 2011) we recruited 41
      patients. The adjusted variables in the logistic regression final model were:
      serum calcium on day three (Odds Ratio 3.5, Confidence Intervals 95%: 1.12 to
      13.61, P < 0.028) and anisocoria (Odds Ratio 8.24, Confidence Intervals 95%: 1.3
      to 67.35, P < 0.019) obtaining an adjusted R2 of 0.22 (P < 0.005). DISCUSSION:
      The serum levels of calcium on day three could be useful for the prediction of
      mortality in patients with moderate and severe TBI.

PMID- 24139089
TI  - Median life span of a cohort of National Institute for Health and Care Excellence
      clinical guidelines was about 60 months.
AB  - OBJECTIVES: To describe the length of time National Institute for Health and Care
      Excellence (NICE) clinical guidelines have remained valid. STUDY DESIGN AND
      SETTING: The present study is a survival analysis of a cohort of published NICE
      clinical guidelines. The National Health Service in England and Wales uses NICE
      clinical practice guidelines as a reference for treatment and care of
      individuals. They need to be updated as new evidence arises, to remain credible
      and relevant, and are currently assessed 3 years after publication. RESULTS:
      Survival analysis suggested that about 86% of guidelines are still up-to-date 3
      years after their publication. The median life span was 60 months (95% confidence
      interval: 51, 69). CONCLUSION: These findings are similar to those in other
      studies of the life span of guidelines. Efficient mechanisms must be in place to
      detect the minority of guidelines that become outdated quickly.

PMID- 24139088
TI  - Effect of stearidonic acid-enriched soybean oil on fatty acid profile and
      metabolic parameters in lean and obese Zucker rats.
AB  - BACKGROUND: Consumption of marine-based oils high in omega-3 polyunsaturated
      fatty acids (n3PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      is known to protect against obesity-related pathologies. It is less clear whether
      traditional vegetable oils with high omega-6 polyunsaturated fatty acid (n6PUFA)
      content exhibit similar therapeutic benefits. As such, this study examined the
      metabolic effects of a plant-based n3PUFA, stearidonic acid (SDA), in polygenic
      obese rodents. METHODS: Lean (LZR) and obese Zucker (OZR) rats were provided
      either a standard westernized control diet (CON) with a high n6PUFA to n3PUFA
      ratio (i.e., 16.2/1.0) or experimental diet modified with flaxseed (FLAX),
      menhaden (FISH), or SDA oil that resulted in n6PUFA to n3PUFA ratios of 1.7/1.0,
      1.3/1.0, and 1.0/0.8, respectively. RESULTS: After 12 weeks, total adiposity,
      dyslipidemia, glucose intolerance, and hepatic steatosis were all greater,
      whereas n3PUFA content in liver, adipose, and muscle was lower in OZR vs. LZR
      rats. Obese rodents fed modified FISH or SDA diets had lower serum lipids and
      hepatic fat content vs. CON. The omega-3 index (i.e., SigmaEPA + DHA in
      erythrocyte membrane) was 4.0, 2.4, and 2.0-fold greater in rodents provided
      FISH, SDA, and FLAX vs. CON diet, irrespective of genotype. Total hepatic n3PUFA
      and DHA was highest in rats fed FISH, whereas both hepatic and extra-hepatic EPA
      was higher with FISH and SDA groups. CONCLUSIONS: These data indicate that SDA
      oil represents a viable plant-derived source of n3PUFA, which has therapeutic
      implications for several obesity-related pathologies.

PMID- 24139090
TI  - Farmers' perception of impacts of bovine trypanosomosis and tsetse fly in
      selected districts in Baro-Akobo and Gojeb river basins, Southwestern Ethiopia.
AB  - BACKGROUND: Trypanosomosis, via causing anaemia, emaciation, production loss and
      death, is arguably the most important constraint to livestock development in Sub
      Saharan countries, including Ethiopia and its impact in Baro-Akobo and Gojeb
      river basins (endemic areas for tsetse flies) is unknown. This study was carried
      out from November 2011 to April 2012 to assess farmers' perception on the
      presence, impact, management and the need of intervention programs of bovine
      trypanosomosis and tsetse fly in selected districts located in Baro-Akobo and
      Gojeb river basins, Southwestern Ethiopia. A standardized questionnaire survey
      was employed to collect the relevant information from the farmers. RESULTS: The
      result of this study showed that 94.1% of the respondents considered bovine
      trypanosomosis as an economically important cattle disease which accounted for
      64.6% of the total annual deaths in the year 2011/2012. Estimated mean annual
      financial loss via mortality due to trypanosomosis was reported to be 3501
      Ethiopian Birr (US$200)/household. The reported trypanosomosis suggestive signs
      were consistent with published reports and farmers strongly associated the
      occurrence of the disease with biting flies (particularly, tsetse fly).
      Respondents also explained that the seasonality of the disease and its vectors,
      i.e. May and June are peak risk months of the year. Chemotherapy was reported the
      major method to combating the problem, mean frequency of treatment being 5.7
      times per animal per year. Because of the economic burden of the disease, farmers
      expressed their strong interest and support for the establishment of intervention
      program in their area. CONCLUSION: The study revealed that livestock keepers are
      familiar with bovine trypanosomosis and its vectors as well as its impacts. Thus,
      trypanosomosis and tsetse control strategies should be integrated with the local
      communities' participation to minimize the impacts of the disease and its vectors
      in the area.

PMID- 24139091
TI  - Cerebral aneurysm presenting with aseptic meningitis: a case report.
AB  - INTRODUCTION: This case highlights the potential importance of new-onset
      headache, even in the absence of other worrisome features, in a patient with a
      cerebral aneurysm. CASE PRESENTATION: A 61-year-old Caucasian woman presented
      with nonspecific insidious onset of headache, a superior cerebellar artery
      aneurysm and cerebrospinal fluid lymphocytosis. She had a subarachnoid hemorrhage
      21 days later, at which time the aneurysm had enlarged. The aneurysm was repaired
      endovascularly and the patient recovered with a modified Rankin score of 1.
      CONCLUSIONS: This case suggests that new onset of chronic headache in a patient
      with an unruptured aneurysm may be due to aneurysm growth and can be associated
      with cerebrospinal fluid lymphocytosis. Headaches are common and may occur
      incidentally in patients with cerebral aneurysms, but new-onset headache, even if
      mild, should prompt consideration for timely aneurysm repair.

PMID- 24139092
TI  - Guanfacine extended release: a novel treatment for attention
      deficit/hyperactivity disorder in children and adolescents.
AB  - BACKGROUND: Guanfacine extended release (GXR) has reported efficacy for the
      treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy and
      adjunctive therapy to psychostimulant medications. OBJECTIVE: The objective of
      this article was to review the efficacy, safety profile, mechanism of action,
      pharmacokinetics, and appropriate dosing of GXR in children and adolescents with
      ADHD. METHODS: Pertinent English-language literature was identified from searches
      of MEDLINE (1950-February 2012), BIOSIS (1969-February 2012), and EMBASE (1974
      February 2012). Search terms included guanfacine, guanfacine extended release,
      attention deficit disorder with hyperactivity, ADHD, nonstimulant, and alpha-2
      adrenergic receptor. Of the 49 publications identified, 12 are reviewed herein.
      Citations from identified articles were reviewed for additional references.
      Abstracts and posters presented at recent scientific meetings and data included
      in the prescribing information were also reviewed. RESULTS: Studies of GXR have
      demonstrated efficacy as once-daily monotherapy as well as adjunctive therapy to
      psychostimulants for ADHD in short-term trials. The safety profile of GXR is
      consistent with that of a centrally acting alpha2A-adrenoceptor agonist.
      Somnolence, sedation, and hypersomnia adverse events (AEs), although frequent,
      are typically mild to moderate and tend to diminish with continued treatment.
      However, 1 long-term, open-label study found that 22 serious treatment-emergent
      AEs occurred in 16 (6.2%) of 259 subjects, and another found that 26% of subjects
      discontinued therapy due to AEs. The cardiovascular effects, of GXR are
      consistent with guanfacine's known effects, and are generally modest in nature.
      The mechanism of action of GXR in ADHD is unknown. Because the pharmacokinetics
      of immediate-release guanfacine differ from GXR, dose substitution on a milligram
      for-milligram basis is inappropriate. Clinical trials analyzed according to
      weight-adjusted doses suggest a dose-response relationship for efficacy. Doses >4
      mg/d cannot be recommended due to lack of study data at those doses. CONCLUSIONS:
      Current evidence indicates that GXR is an effective treatment option for children
      and adolescents with ADHD. AEs are typically mild to moderate, although severe
      AEs and discontinuations due to AEs have been observed.

PMID- 24139093
TI  - Kyphoplasty for vertebral augmentation in the elderly with osteoporotic vertebral
      compression fractures: scenarios and review of recent studies.
AB  - BACKGROUND: Vertebral compression fractures caused by osteoporosis are among the
      most common fractures in the elderly. The treatment focuses on pain control,
      maintenance of independence, and management of the osteoporosis. Elderly patients
      often encounter adverse effects to pain medications, do not tolerate bed rest,
      and are not ideal candidates for invasive spinal reconstructive surgery.
      Percutaneous vertebral augmentation (vertebroplasty or kyphoplasty) has become
      popular as a less-invasive alternative. However, studies have questioned the
      effectiveness of these procedures. METHODS: The authors conducted a MEDLINE
      search using relevant search terms including osteoporosis, osteoporotic vertebral
      compression fracture, elderly, kyphoplasty and vertebroplasty. CASE
      SUMMARY/RESULTS: Two elderly patients presented with a fracture of their third
      and first lumbar vertebral body, respectively. One patient progressed well with
      conservative treatment, whereas the other patient was hospitalized secondary to
      pain after conservative measures failed to offer improvement. The hospitalized
      patient subsequently opted for a kyphoplasty and was able to resume his normal
      daily activities after the procedure. CONCLUSIONS: Selecting patients on an
      individual case-by-case basis can optimize the effectiveness and outcomes of a
      vertebral augmentation. This process includes the documentation of an
      osteoporotic vertebral compression fracture with the aide of imaging studies,
      including the acuity of the fracture as well as the correlation with the physical
      examination findings. Patients who are functional and improving under a
      conservative regimen are not candidates for kyphoplasty. However, if the
      conservative management is not successful after 4 to 6 weeks and the patient is
      at risk to become bedridden, an augmentation should be considered. A kyphoplasty
      procedure may be preferred over vertebroplasty, given the lower risk profile and
      better outcomes regarding spinal alignment.

PMID- 24139094
TI  - Pain therapeutics in older adults.

PMID- 24139098
TI  - Editors' pick: transcriptomes of 1000 genomes.

PMID- 24139096
TI  - The hypolipidemic effect of cilostazol can be mediated by regulation of hepatic
      low-density lipoprotein receptor-related protein 1 (LRP1) expression.
AB  - OBJECTIVES: Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, is a
      vasodilator and an anti-thrombotic agent. The mechanism whereby cilostazol
      reduces plasma triglyceride is not completely understood. Here we investigated
      the effect of cilostazol on a remnant lipoprotein receptor, low-density
      lipoprotein receptor-related protein 1 (LRP1), which has been reported to play an
      essential role in clearance of circulating triglyceride in the liver.
      MATERIALS/METHODS: Total cellular expression, and functional and transcriptional
      regulation of LRP1 were analyzed in human hepatocarcinoma cell lines incubated
      with cilostazol. Also, C57BL/6 mice were subjected to high-fat diet (60% kcal)
      and cilostazol (30 mg/kg) treatment for 10 weeks. RESULTS: Cilostazol increased
      both mRNA and protein expression of LRP1 in HepG2 and Hep3B cells. In addition,
      enhanced transcriptional activity of the LRP1 promoter containing a peroxisome
      proliferator response element (PPRE) was observed after cilostazol exposure.
      Cilostazol treatment enhanced the uptake of lipidated apoE3, and this effect was
      abolished when LRP1 was silenced by siRNA knockdown. High-fat diet induced
      hyperglycemia with high level of plasma triglycerides, and reduced hepatic LRP1
      expression in mice. Treatment with cilostazol for the same period of time,
      however, successfully prevented this down-regulation of LRP1 expression and
      reduced plasma triglycerides. CONCLUSION: Taken together, our results
      demonstrated that cilostazol enhances LRP1 expression in liver by activating
      PPARgamma through the PPRE in the LRP1 promoter. Increased hepatic LRP1 may be
      essential for the reduction of circulating triglycerides brought about by
      cilostazol.

PMID- 24139099
TI  - Sharp changes in tobacco products affordability and the dynamics of smoking
      prevalence in various social and income groups in Ukraine in 2008-2012.
AB  - BACKGROUND: To curb the tobacco epidemic, successful implementation of tobacco
      control measures should take into account how specific demographic groups react
      to particular policies. In 2005-2010, Ukraine experienced a sharp decline in
      smoking prevalence. In 2008-2010, several excise tax hikes combined with the
      economic recession resulted in a sharp reduction of tobacco product
      affordability, but in 2011-2012 tax increases were rather moderate. The aim of
      the current research was to investigate how smoking prevalence in various gender,
      social and income groups in Ukraine changed in response to differing tobacco
      taxation policies in 2008-2012. METHODS: The State Statistics Service of Ukraine
      annual household surveys among the population aged 12 years and older, which
      include questions about smoking, were used. The aggregate data from the annual
      household surveys datasets of 2008-2012 were analyzed. RESULTS: The decline in
      general smoking prevalence was much steeper in 2008-2010 - 3.2 percentage points
      in two years, while in two subsequent years it constituted only 0.6 percentage
      points. Smoking prevalence declined in all age, social, and income groups in 2008
      2010. However, in 2011-2012 smoking prevalence continued to decline mainly among
      young and poor people, while some older and more affluent smokers apparently
      relapsed to smoking. CONCLUSIONS: Short-term and long-term price responsiveness
      of tobacco demand by socioeconomic status of population groups in low--and middle
      -income countries like Ukraine could be rather different for poor and more
      affluent people. Tobacco excise tax hikes have great potential in reducing
      smoking prevalence, especially in young and less affluent people, however they
      should also be supported by effective and available smoking cessation services.

PMID- 24139100
TI  - The efficiency of the public dental services (PDS) in Cyprus and selected
      determinants.
AB  - BACKGROUND: Currently there is a dual system of oral healthcare delivery in
      Cyprus: the public dental system (PDS) run by the Government and the private
      system provided by private dental practitioners. Although 83% of the population
      is entitled to free treatment by the PDS only 10% of the population make use of
      them. As Cyprus faces now the challenges of the introduction of a new health care
      system and rising healthcare costs in general, surveys that examine, among other
      things, the efficiency of the PDS become very important as tools to make
      important cost savings. The aims of this study are to assess trends regarding the
      number of visits and the age distribution of patients using PDS from 2004 to
      2007, to measure the technical efficiency of the PDS and to investigate various
      factors that may affect it. METHODS: Non-parametric Data Envelopment Analysis
      (DEA) was employed to assess technical efficiency. Two separate cases were
      examined. Efficiency was calculated, firstly using as inputs the wages and the
      working hours of the personnel, and secondly the working hours of the personnel
      and the cost of the materials. As outputs, in both cases, the treatment offered
      (divided into primary, secondary and tertiary care) and the numbers of visits
      were used. In the second stage Tobit analysis was used to explore various
      predictors of efficiency (time per patient, location, age of dentists, age of
      patients and age of assistants). RESULTS: The study showed that whilst there was
      an increase in the number of patients using the PDS from 2004 to 2007, only a
      small proportion of the population (10%) make use of them. Women, middle and
      older aged patients, make more use of the PDS. Regarding efficiency, there were
      large differences between the units. The average Technical Efficiency score was
      68% in the first model and 81% in the second. Urban areas and low time per
      patient are predictors of increased efficiency. CONCLUSION: The results suggest
      that many of the rural PDS are underperforming. Given that the option of shutting
      them down is undesirable, measures should be taken to reduce inputs (e.g. by
      reducing the personnel's working hours) and to increase outputs (remove barriers,
      make PDS more accessible and increase the number of patients).

PMID- 24139101
TI  - Inaugural address by the new president of the Japan Prosthodontic Society-
      Promoting prosthetic dental practice as a contributor to society.

PMID- 24139102
TI  - [Cervical spine osteochondroma presenting with torticollis and hemiparesis].
AB  - Osteochondromas are slow-growing benign bone tumors that are located frequently
      in the long bones. Approximately 1-4% of them occur in the spine. Solitary spinal
      osteochondromas may produce a wide variety of symptoms depending on their
      location and relationship to associated structures. We report a case of a 74-year
      old woman who was admitted to our hospital with complaints of progressive left
      hemibody weakness and cervicalgia. Neurological examination disclosed mild left
      sided hemiparesis and left torticollis. Computed tomography and magnetic
      resonance imaging of the cervical spine revealed an expansive lesion affecting
      the left C3-C4 facet joint. The patient underwent a posterior C3 and C4
      hemilaminectomy, complete excision of the lesion and instrumented posterior
      cervical fixation. Histological examination confirmed the diagnosis of
      osteochondroma. After surgery her symptoms improved progressively with no
      neurological sequels. 

PMID- 24139103
TI  - Comparisons of statistical models to predict fecal indicator bacteria
      concentrations enumerated by qPCR- and culture-based methods.
AB  - Recently, the United States Environmental Protection Agency (USEPA) revised their
      recreational water quality criteria, in which adjustments were made by approving
      enterococci (ENT) quantitative PCR (qPCR) as an alternative, rapid method and
      advocating the use of predictive models for water quality management. The
      implementation of qPCR-based methods and prediction models are meant to decrease
      the time between sample collection and public advisories and notifications. To
      date, few studies have compared qPCR-based models to culture-based prediction
      models and none of these studies have been conducted in coastal estuarine
      systems. In this study, we created prediction models using qPCR-based fecal
      indicator bacteria (FIB) data in dual-use recreational and shellfish harvesting
      waters and compared them to published ENT and Escherichia coli (EC) culture-based
      prediction models in eastern North Carolina estuaries. Furthermore, an empirical
      statistical model was created to predict qPCR inhibition levels so that proper
      remediation techniques can be applied when it is a problem. Predictor variable
      selection in both qPCR- and culture-based ENT models was very similar; both
      models included 14-day rain total, dissolved oxygen, and salinity/conductivity,
      with 89 and 90% of qPCR and culture data described, respectively. Using ENT
      management action thresholds, qPCR- and culture-based models showed high accuracy
      in management decisions. The qPCR model had 92 and 96% accuracy using the 110 and
      1000 cell equivalents (CE)/100 ml thresholds, respectively, and the culture model
      had 90% accuracy in management decisions with the 110 MPN/100 ml threshold. EC
      models for qPCR- and culture-based concentrations used similar independent
      variables (14-day humidity, salinity/conductivity, a rain/storm variable, and a
      measure of air temperature), with each model explaining 26 and 55% of the data
      variation, respectively. When using different thresholds that were logs apart for
      management decisions, the two EC models accurately predicted management
      decisions; qPCR models correctly predicted management decisions 96 and 77% of the
      time (using 31 and 320 CE/100 ml, respectively) while culture models correctly
      predicted management decisions 96 and 88% percent of the time (with 31 and 320
      MPN/100 ml, respectively). Equivalency between models was shown in our non-point
      source impacted estuaries, with ENT models performing slightly better than EC
      models. In addition, inhibition of the qPCR was a major issue that had to be
      addressed. An inhibition model was created with easily obtained meteorological
      data and accounted for a high level of data variability (adjusted R(2) = 0.82).

PMID- 24139104
TI  - Bench-scale study of the effect of phosphate on an aerobic iron oxidation plant
      for mine water treatment.
AB  - At the opencast pit Nochten acidic iron- and sulfate-rich mine waters are treated
      biotechnologically in a mine-water treatment plant by microbial iron oxidation.
      Due to the low phosphate concentration in such waters the treatment plant was
      simulated in bench-scale to investigate the influence of addition of potassium
      dihydrogen phosphate on chemical and biological parameters of the mine-water
      treatment. As a result of the phosphate addition the number of cells increased,
      which resulted in an increase of the iron oxidation rate in the reactor with
      phosphate addition by a factor of 1.7 compared to a reference approach without
      phosphate addition. Terminal restriction fragment length polymorphism (T-RFLP)
      analysis during the cultivation revealed a shift of the microbial community
      depending on the phosphate addition. While almost exclusively iron-oxidizing
      bacteria related to "Ferrovum" sp. were detected with phosphate addition, the
      microbial community was more diverse without phosphate addition. In the latter
      case, iron-oxidizing bacteria ("Ferrovum" sp., Acidithiobacillus spp.) as well as
      non-iron-oxidizing bacteria (Acidiphilium sp.) were identified.

PMID- 24139105
TI  - On the cause of the tailing phenomenon during virus disinfection by chlorine
      dioxide.
AB  - This study investigates the mechanisms underlying the deviation from Chick-Watson
      kinetics, namely a tailing curve, during the disinfection of viruses by chlorine
      dioxide (ClO2). Tailing has been previously reported, but is typically attributed
      to the decay in disinfectant concentration. Herein, it is shown that tailing
      occurs even at constant ClO2 concentrations. Four working hypothesis to explain
      the cause of tailing were tested, specifically changes in the solution's
      disinfecting capacity, aggregation of viruses, resistant virus subpopulations,
      and changes in the virus properties during disinfection. In experiments using MS2
      as a model virus, it was possible to rule out the solution's disinfecting
      capacity, virus aggregation and the resistant subpopulation as reasons for
      tailing. Instead, the cause for tailing is the deposition of an adduct onto the
      virus capsid over the course of the experiment, which protects the viruses. This
      adduct could easily be removed by washing, which restored the susceptibility of
      the viruses to ClO2. This finding highlights an important shortcoming of ClO2,
      namely its self-limiting effect on virus disinfection. It is important to take
      this effect into account in treatment applications to ensure that the water is
      sufficiently disinfected before human consumption.

PMID- 24139106
TI  - Enzyme augmentation of an anaerobic membrane bioreactor treating sewage
      containing organic particulates.
AB  - Hydrolytic enzymes offer the potential for enhancing the hydrolysis of organic
      particulates, which tends to be rate limiting in the anaerobic treatment of
      particulate containing wastewaters. In this study, the effects of enzyme
      augmentation on the biological performance of a laboratory submerged anaerobic
      membrane bioreactor (AnMBR) were investigated. A hydrolytic enzyme blend
      containing proteases, amylases and lipases was added to the bioreactor daily at
      doses ranging from 0.9 to 18 mL/g of influent COD to enhance the hydrolysis of
      organic particulates and soluble macromolecules. Enhanced enzymatic hydrolysis
      resulted in the reduction of total and volatile suspended solids by approximately
      19% and 22%, respectively, on the average. Overall COD removal efficiency was
      unaffected while the average biogas production increased from 0.27 to 0.34 L/g of
      influent COD. Additionally, the concentrations of bound extracellular polymeric
      substances (EPS) and soluble microbial products (SMP) decreased and increased
      respectively, suggesting the enzymatic hydrolysis of EPS to SMP. Low enzymatic
      activities were detected throughout the entire study, probably due to the
      instability of free enzymes in the bioreactor environment. Nevertheless, membrane
      retention of exogenous enzymes within the AnMBR is an inherent feature, as
      evidenced by size exclusion chromatography.

PMID- 24139107
TI  - Truth versus myth on mental illness, suicide, and crime.

PMID- 24139108
TI  - Integrity in research collaborations: the Montreal Statement.

PMID- 24139109
TI  - The GAVI Alliance--successes and ongoing challenges.

PMID- 24139110
TI  - Reversing the tide of the UK tuberculosis epidemic.

PMID- 24139112
TI  - Esther Madudu: standing up for mothers in Africa.

PMID- 24139113
TI  - Exercise for depression in elderly people - Authors' reply.

PMID- 24139114
TI  - Exercise for depression in elderly people.

PMID- 24139115
TI  - Children outcomes and intimate partner violence research.

PMID- 24139116
TI  - Community health workers: an opportunity for reverse innovation.

PMID- 24139117
TI  - Children outcomes and intimate partner violence research - Authors' reply.

PMID- 24139118
TI  - Community health workers: an opportunity for reverse innovation - Authors' reply.

PMID- 24139119
TI  - Chemical poisoning-related injury in China.

PMID- 24139120
TI  - Tobacco control in Ukraine and Russia.

PMID- 24139121
TI  - Anaphylaxis caused by mosquito allergy in systemic mastocytosis.

PMID- 24139122
TI  - Microcystic macular edema: retrograde maculopathy caused by optic neuropathy.
AB  - PURPOSE: To investigate retrograde axonal degeneration for its potential to cause
      microcystic macular edema (MME), a maculopathy that has been previously described
      in patients with demyelinating disease. To identify risk factors for MME and to
      expand the anatomic knowledge on MME. DESIGN: Retrospective case series.
      PARTICIPANTS: We included 117 consecutive patients and 180 eyes with confirmed
      optic neuropathy of variable etiology. Patients with glaucoma were excluded.
      METHODS: We determined age, sex, visual acuity, etiology of optic neuropathy, and
      the temporal and spatial characteristics of MME. Eyes with MME were compared with
      eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer
      segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME
      MEASURES: Demographic data, distribution of MME in the retina, and thickness of
      retinal layers were analyzed. RESULTS: We found MME in 16 eyes (8.8%) from 9
      patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME
      was restricted to the inner nuclear layer (INL) and had a characteristic
      perifoveal circular distribution. Compared with healthy controls, MME was
      associated with significant thinning of the ganglion cell layer and nerve fiber
      layer, as well as a thickening of the INL and the deeper retinal layers. Youth is
      a significant risk factor for MME. CONCLUSIONS: Microcystic macular edema is not
      specific for demyelinating disease. It is a sign of optic neuropathy irrespective
      of its etiology. The distinctive intraretinal anatomy suggests that MME is caused
      by retrograde degeneration of the inner retinal layers, resulting in impaired
      fluid resorption in the macula.

PMID- 24139123
TI  - Intravitreal bevacizumab at 4-month intervals for prevention of macular edema
      after plaque radiotherapy of uveal melanoma.
AB  - PURPOSE: To evaluate the efficacy of intravitreal bevacizumab for prevention of
      macular edema after plaque radiotherapy of uveal melanoma. DESIGN: Retrospective,
      single-center, nonrandomized, interventional comparative study. PARTICIPANTS:
      Patients with uveal melanoma treated with plaque radiotherapy were divided into 2
      groups: a bevacizumab group and a control group. INTERVENTION: The bevacizumab
      group received intravitreal bevacizumab injection at the time of plaque removal
      and every 4 months thereafter for 2 years (total, 7 injections). The control
      group had no intravitreal bevacizumab injection. Both groups had periodic follow
      up with ophthalmoscopy and optical coherence tomography (OCT). MAIN OUTCOME
      MEASURES: Development of OCT-evident macular edema. RESULTS: There were 292
      patients in the bevacizumab group and 126 in the control group. The median
      foveolar radiation dose was 4292 cGy (bevacizumab) and 4038 cGy (control; P =
      0.327). The cumulative incidence of OCT-evident macular edema over 2 years
      (bevacizumab group vs. control group) was 26% versus 40% (P = 0.004),
      respectively; that for clinically evident radiation maculopathy was 16% versus
      31% (P = 0.001), respectively; that for moderate vision loss was 33% versus 57%
      (P < 0.001), respectively; and that for poor visual acuity was 15% versus 28% (P
      = 0.004), respectively. There was no statistically significant difference in
      clinically evident radiation papillopathy (P = 0.422). Kaplan-Meier estimates at
      2 years showed statistically significantly reduced rates of OCT-evident macular
      edema (P = 0.045) and clinically evident radiation maculopathy (P = 0.040) in the
      bevacizumab group compared with controls. CONCLUSIONS: Patients receiving
      intravitreal bevacizumab injection every 4 months after plaque radiotherapy for
      uveal melanoma demonstrated OCT-evident macular edema, clinically evident
      radiation maculopathy, moderate vision loss, and poor visual acuity less
      frequently over a period of 2 years than patients not receiving the injections.

PMID- 24139124
TI  - Combining cataract surgery with 25-gauge high-speed pars plana vitrectomy:
      results from a retrospective study.
AB  - PURPOSE: To report postoperative complications in eyes that underwent 25-gauge
      high-speed pars plana vitrectomy (25G HS-PPV) alone or combined with phaco
      vitrectomy surgery for epiretinal membrane, vitreomacular traction, or macular
      hole. DESIGN: Retrospective, interventional case series. PARTICIPANTS: A total of
      565 eyes were included in this study of vitreoretinal surgery performed from
      April 2011 to June 2012 by a single surgeon. METHODS: Eyes were divided into 2
      groups: group A included eyes that underwent phacoemulsification combined with
      25G HS-PPV (348 eyes), and group B included pseudophakic eyes that underwent 25G
      HS-PPV alone (217 eyes). Follow-up was from a minimum of 4 months to a maximum of
      14 months. MAIN OUTCOME MEASURES: To evaluate and statistically compare the
      postoperative complications of these 2 surgical groups. RESULTS: During the
      follow-up, retinal detachment (RD) developed in 10 eyes (1.77%): 4 in group A and
      6 in group B. Cystoid macular edema (CME) occurred in 5 eyes (0.87%): 3 in group
      A and 2 in group B. In 1 eye in group A, a dislocation in the anterior chamber of
      the posterior chamber intraocular lens was observed (0.18%). The statistical
      analysis, evaluated by the Fisher exact test, did not show a significant
      postoperative difference between these 2 surgical groups for RD (P = 0.19) or CME
      (P = 1.00). CONCLUSIONS: The combination of cataract or lens phacoemulsification
      with 25G HS-PPV for vitreomacular diseases did not result in an increase in
      postoperative complications compared with 25G HS-PPV alone performed in
      pseudophakic eyes.

PMID- 24139125
TI  - Length of day during early gestation as a predictor of risk for severe
      retinopathy of prematurity.
AB  - PURPOSE: Fetal mice require light exposure in utero during early gestation for
      normal vascular development in the eye. Because angiogenic abnormalities in
      retinopathy of prematurity (ROP) are manifested in preterm infants, we
      investigated whether day length during early gestation was associated with severe
      ROP (SROP). DESIGN: Single-center, retrospective cohort study. PARTICIPANTS: We
      included a total of 343 premature infants (401-1250 g birth weight [BW], from
      1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing
      SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in
      zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated.
      METHODS: For each infant, average day length (ADL) was calculated during
      different cumulative time periods and time windows after the estimated date of
      conception (EDC). Multiple logistic regression analysis (with generalized
      estimating equations to account for inter-eye correlation) was performed. MAIN
      OUTCOME MEASURES: Association of ADL during early gestation with SROP. RESULTS:
      In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational
      age, multiple births, race, per capita income in the mother's residence ZIP code,
      and ADL during the first 90 days after the EDC were factors associated with the
      development of SROP. Each additional hour of ADL (90 days) decreased the
      likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence
      interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold
      ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the
      first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001;
      OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated
      with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and
      the prethreshold ROP eyes models, respectively. CONCLUSIONS: Higher ADL during
      early gestation was associated with a lower risk for SROP and may imply a role
      for prophylactic light treatment during early gestation to decrease the risk of
      SROP.

PMID- 24139126
TI  - The latitudinal biodiversity gradient through deep time.
AB  - Today, biodiversity decreases from equatorial to polar regions. This is a
      fundamental pattern governing the distribution of extant organisms, the
      understanding of which is critical to predicting climatically driven biodiversity
      loss. However, its causes remain unresolved. The fossil record offers a unique
      perspective on the evolution of this latitudinal biodiversity gradient (LBG),
      providing a dynamic system in which to explore spatiotemporal diversity
      fluctuations. Deep-time studies indicate that a tropical peak and poleward
      decline in species diversity has not been a persistent pattern throughout the
      Phanerozoic, but is restricted to intervals of the Palaeozoic and the past 30
      million years. A tropical peak might characterise cold icehouse climatic regimes,
      whereas warmer greenhouse regimes display temperate diversity peaks or flattened
      gradients. 

PMID- 24139128
TI  - Monitoring of children with acute gastroenteritis in Madrid, Spain, during 2010
      2011: rotavirus genotype distribution after the vaccines introduction.
AB  - BACKGROUND AND OBJECTIVES: A structured surveillance study was conducted on
      children with diarrhea who were hospitalized in Madrid (Spain) during 2010-2011,
      in order to describe temporal, geographic, and age-related trends in rotavirus
      (RV) strains after the introduction of the RV vaccines in our country. STUDY
      DESIGN AND RESULTS: A total of 370 children were enrolled, with RV being detected
      in 117 (31.6%) cases. Coinfections were detected mainly with rotavirus,
      astrovirus and norovirus. The most prevalent rotavirus G type was G1 (60.7%)
      followed by G2 (16.09%), G9 (5.9%), and G12 (5.1%). The G12 genotype appeared for
      the first time in 2008 in Spain, and it has increased to 5.1% of the cases in
      this report. Some uncommon P genotypes, such as P[14] and P[6], both with a low
      percentage, were found. The samples with G1 G2, G9 and G12 genotypes appeared in
      all ages, but were significantly higher in children under 2 years old.
      CONCLUSION: A long-term structured surveillance is required in the Spanish post
      vaccine era, in order to determine the prevalence and variability of RV
      genotypes. This will especially be needed to distinguish between changes
      occurring as a result of natural fluctuation in genotype or those (changes) that
      could be mediated by population immunity to the vaccines. In addition, it will be
      necessary to study the impact of the current vaccines on the circulating
      rotavirus strains and on the overall reduction in the prevalence of rotavirus
      disease among children in Spain.

PMID- 24139127
TI  - Acute oral intake of a higenamine-based dietary supplement increases circulating
      free fatty acids and energy expenditure in human subjects.
AB  - BACKGROUND: Higenamine, also known as norcoclaurine, is an herbal constituent
      thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating
      lipolysis. It was the purpose of this study to determine the impact of a
      higenamine-based dietary supplement on plasma free fatty acids and energy
      expenditure following acute oral ingestion. METHODS: Sixteen healthy subjects (8
      men; 26.1 +/- 2.5 yrs; 8 women 22.4 +/- 3.1 yrs) ingested a dietary supplement
      containing a combination of higenamine, caffeine (270 mg), and yohimbe bark
      extract or a placebo, on two separate occasions in a double-blind, randomized,
      cross-over design, separated by 6-8 days. Blood samples were collected
      immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion,
      and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were
      collected at the same times for a measure of kilocalorie expenditure and
      respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood
      pressure were recorded at all times. Data collection occurred in the morning
      following a 10 hour overnight fast. RESULTS: A condition effect was noted for
      both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher
      for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No
      statistically significant effects were noted for glycerol or RER (p > 0.05). A
      condition effect was noted for heart rate (p = 0.03) and systolic blood pressure
      (p < 0.0001), with values higher for supplement compared to placebo. CONCLUSION:
      Ingestion of a higenamine-based dietary supplement stimulates lipolysis and
      energy expenditure, as evidenced by a significant increase in circulating FFA and
      kilocalorie expenditure. The same supplement results in a moderate increase in
      heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent
      with previous studies evaluating moderate doses of caffeine and yohimbine,
      suggesting that higenamine contributes little to the increase in these
      hemodynamic variables. These findings are in reference to young, healthy and
      active men and women.

PMID- 24139129
TI  - [Microbiological diagnosis of emerging arboviral and rodent borne diseases].
AB  - Vector borne viruses (VBV) include viruses transmitted by arthropods, rodents and
      other animals. In Spain the three main autochthonous VBVs causing human diseases
      are: Toscana, West Nile and Lymphocytic Choriomeningitis viruses. There are also
      other imported viruses that are potential threats to our public health, due to
      the presence of competent transmission vectors (dengue and chikungunya viruses in
      areas infested with Aedes albopictus), or due to the potential person-to-person
      transmission (Lassa and other viruses causing haemorrhagic fever). The Spanish
      Society for Infectious Diseases and Clinical Microbiology has responded to the
      emergence of VBVs by publishing a special issue of Microbiological Proceedings
      focused on the diagnosis of those emerging vector borne viruses of major concern
      in our country. 

PMID- 24139130
TI  - [Perceptions of Alicante (Spain) doctors on the 2009 influenza pandemic].

PMID- 24139131
TI  - Trends in using beta-blockers and methyldopa for hypertensive disorders during
      pregnancy in a Canadian population.
AB  - OBJECTIVE: To describe trends in and patterns of antihypertensive drug use in a
      general obstetric population. STUDY DESIGN: Historical cohort study. A total of
      18,117 women who gave birth in a Saskatchewan hospital between January 1, 1980
      and December 31, 2005 with a diagnosis of hypertensive disorders in pregnancy
      were identified and included in the analysis. RESULTS: The rate of treatment with
      antihypertensive drugs for pregnant women with chronic hypertension rose from
      19.94% in 1980-1984 to 37.63% in 2000-2005. There were similar increases in
      antihypertensive drug use from 1.51% to 14.47% for gestational hypertension/non
      severe preeclampsia, and from 1.56% to 20.86% for severe preeclampsia/eclampsia.
      Methyldopa was the most frequently used drug, followed by beta-blockers, with
      other antihypertensive drugs accounting for about 18.43% of total uses. The use
      of both methyldopa and labetalol has increased in recent years while the use of
      other antihypertensive drugs has decreased. Other antihypertensive drugs were
      more commonly prescribed in earlier gestation, while methyldopa and labetalol
      were generally prescribed in later gestation. CONCLUSION: The use of
      antihypertensive drugs in pregnancy is relatively common and is increasing, with
      the liberal use of methyldopa and (especially) labetalol contributing appreciably
      to this increase.

PMID- 24139132
TI  - Predicting the success of vaginal surgery: a quantitative risk assessment model
      for future investigation.
AB  - OBJECTIVE: To introduce a model incorporating expected risks for a vaginal
      procedure based on objective measurements of a patient's characteristics and
      propose it as a potential tool to assist in the selection of candidates for
      vaginal surgery. STUDY DESIGN: A quantitative model consisting of 13 clinical
      variables identified as risk factors in a prospective vaginal procedure was
      developed. Medical records of 315 women undergoing a set of routine gynecological
      surgeries via the vaginal, laparoscopic, and abdominal routes were obtained
      during January 2010 and November 2011. These surgeries included hysterectomy,
      myomectomy, bilateral or unilateral salpingo-oophorectomy and adnexal cystectomy.
      After that, each patient was scored according to the model. Sensitivity and
      specificity of the model were analyzed in one data set (cohort I) by receiver
      operating characteristic (ROC) curve and independently validated in a second data
      set (cohort II). RESULTS: 175 patients were included in cohort I while the other
      140 patients formed cohort II. The intra- and post-operative complication rates
      were 0.6% and 0%, respectively. A vaginal procedure was predicted with good
      accuracy (AUC=0.852). The sensitivity was 86.0% and specificity was 72.0% at an
      optimal cut-off point of score=3. The predication accuracy of this model was
      further validated in cohort II and reached as high as 85.7%. Furthermore, the
      score was significantly associated with the volume of estimated blood loss and
      the duration of operation time (P<0.05). CONCLUSION: Our quantitative risk
      assessment model predicts safe vaginal surgery with good accuracy. Predictive
      tools based on such a model could help surgeons to optimize patient selection and
      thus contribute to reducing costs while enhancing patients' satisfaction. We
      invite other researchers to modify and validate the model in other populations.

PMID- 24139133
TI  - Prevalence and epidemiological correlates and treatment outcome of HCV infection
      in an Italian prison setting.
AB  - BACKGROUND: The aim of the present study is to test in the feasibility of a
      screening programme for HCV infection in an Italian prison and to evaluate the
      treatment outcomes. METHOD: Single-centre cross-sectional study carried out in
      Milan-Opera. The HCV infection prevalence was calculated on the imprisoned
      population on the January 31 2006, the data on treatment over the following 2
      years. Treatment option offered to HCV chronically infected patients was then
      analysed, reasons for not being treated was evaluated. RESULTS: Of the 965
      inmates, 695 were enrolled in the study, 682 (98%) were males, the median age was
      43 years. There were 131 (18.8%) foreigners and 564 (81.2%) Italians. HCV
      seroprevalence was 22.4%(95% CI:19.4%-25.7%), 60 subjects (38.4%) being HIV co
      infected too. Prevalence of HCV infection was significantly higher in HIVAb
      positive (89.6%; 95% CI:79.7%-95.7%) than in HIVAb negative (15.15%; 95% CI 12.6%
      18.3%) (p<0.001). Among Italian inmates HCVAb positivity was significantly higher
      than among foreigners (p=0.0154). Among HCVAb positive patients, 135 subjects
      were HCV-RNA positive. Forty-seven (36%) had major clinical contraindication to
      treatment, 18 (13%) refused the treatment, 7 (5%) moved to other Institute and 27
      (20%) were not evaluated by infectious disease specialists. Fifteen patients
      (43%) who received treatment were considered responders, 9 (26%) were non
      responders/relapsers, 6 (17%) interrupted treatment due to side effects and 5
      (14%) were released during treatment and lost in follow-up. CONCLUSIONS: This
      study indicates that the proportion of patients in a prison setting receiving
      diagnosis and treatment for HCV infection remained low.

PMID- 24139134
TI  - Automatic extraction of retinal features from colour retinal images for glaucoma
      diagnosis: a review.
AB  - Glaucoma is a group of eye diseases that have common traits such as, high eye
      pressure, damage to the Optic Nerve Head and gradual vision loss. It affects
      peripheral vision and eventually leads to blindness if left untreated. The
      current common methods of pre-diagnosis of Glaucoma include measurement of Intra
      Ocular Pressure (IOP) using Tonometer, Pachymetry, Gonioscopy; which are
      performed manually by the clinicians. These tests are usually followed by Optic
      Nerve Head (ONH) Appearance examination for the confirmed diagnosis of Glaucoma.
      The diagnoses require regular monitoring, which is costly and time consuming. The
      accuracy and reliability of diagnosis is limited by the domain knowledge of
      different ophthalmologists. Therefore automatic diagnosis of Glaucoma attracts a
      lot of attention. This paper surveys the state-of-the-art of automatic extraction
      of anatomical features from retinal images to assist early diagnosis of the
      Glaucoma. We have conducted critical evaluation of the existing automatic
      extraction methods based on features including Optic Cup to Disc Ratio (CDR),
      Retinal Nerve Fibre Layer (RNFL), Peripapillary Atrophy (PPA), Neuroretinal Rim
      Notching, Vasculature Shift, etc., which adds value on efficient feature
      extraction related to Glaucoma diagnosis. 

PMID- 24139136
TI  - Serum cystatin C and cerebral microbleeds in patients with acute cerebral stroke.
AB  - Recent studies have shown that kidney dysfunction is associated with cerebral
      microbleeds (CMB). Cystatin C is a more useful measurement than creatinine-based
      estimating equations for evaluating kidney function. The purpose of this study
      was to clarify the relationship between cystatin C levels and CMB in patients
      with acute cerebral stroke. This cross-sectional study included a total of 485
      patients with acute ischemic stroke and 129 patients with cerebral hemorrhage.
      The serum levels of cystatin C were significantly higher in acute cerebral stroke
      patients with CMB than in those without (p<0.001). Multivariate logistic
      regression analyses showed that for each single standard deviation increase of
      cystatin C levels, there was a significant increase in the presence of CMB after
      adjusting for age and sex, and after additional adjustment for cardiovascular
      risk factors, silent lacunar infarction, and white matter hyperintensity in
      patients with acute stroke. The odds ratio (95% confidence interval) in patients
      with acute cerebral infarction and cerebral hemorrhage were 2.92 (1.81-6.93) and
      2.98 (1.76-6.97), respectively. The present study suggests that elevated levels
      of cystatin C are associated with the presence of CMB in acute stroke patients,
      independent of conventional risk factors. 

PMID- 24139135
TI  - Multimodal noninvasive and invasive imaging of extracranial venous abnormalities
      indicative of CCSVI: results of the PREMiSe pilot study.
AB  - BACKGROUND: There is no established noninvasive or invasive diagnostic imaging
      modality at present that can serve as a 'gold standard' or "benchmark" for the
      detection of the venous anomalies, indicative of chronic cerebrospinal venous
      insufficiency (CCSVI). We investigated the sensitivity and specificity of 2
      invasive vs. 2 noninvasive imaging techniques for the detection of extracranial
      venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral
      veins (VVs) in patients with multiple sclerosis (MS). METHODS: The data for this
      multimodal imaging comparison pilot study was collected in phase 2 of the
      "Prospective Randomized Endovascular therapy in Multiple Sclerosis" (PREMiSe)
      study using standardized imaging techniques. Thirty MS subjects were screened
      initially with Doppler sonography (DS), out of which 10 did not fulfill
      noninvasive screening procedure requirements on DS that consisted of >=2 venous
      hemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS
      were enrolled into the multimodal diagnostic imaging study. For magnetic
      resonance venography (MRV), IJVs abnormal findings were considered absent or
      pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities
      of the VVs were determined only using non-invasive testing. Catheter venography
      (CV) was considered abnormal when >=50% lumen restriction was detected, while
      intravascular ultrasound (IVUS) was considered abnormal when >=50% restriction of
      the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive
      and invasive imaging modality comparisons between left, right and total IJVs and
      between the VVs and azygos vein were performed. Because there is no reliable way
      of non-invasively assessing the azygos vein, the VVs abnormalities detected by
      the non-invasive testing were compared to the azygos abnormalities detected by
      the invasive testing. All image modalities were analyzed in a blinded manner by
      more than one viewer, upon which consensus was reached. The sensitivity and
      specificity were calculated using contingency tables denoting the presence or
      absence of vein-specific abnormality findings between all imaging modalities used
      individually as the benchmark. RESULTS: The sensitivity of CV + IVUS was 68.4%
      for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs,
      compared to venous anomalies detected on DS. Compared to the venous anomalies
      detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left
      IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9%
      and 11.8%, respectively. The sensitivity between the two invasive imaging
      techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for
      the azygos vein but the IVUS showed a higher rate of venous anomalies than the
      CV. There was excellent correspondence between identifying collateral veins on
      MRV and CV. CONCLUSIONS: Noninvasive DS screening for the detection of venous
      anomalies indicative of CCSVI may be a reliable approach for identifying patients
      eligible for further multimodal invasive imaging testing of the IJVs. However,
      the noninvasive screening methods were inadequate to depict the total amount of
      azygos vein/VVs anomalies identified with invasive testing. This pilot study,
      with limited sample size, shows that both a non-invasive and invasive multimodal
      imaging diagnostic approach should be recommended to depict a range of
      extracranial venous anomalies indicative of CCSVI. However, lack of invasive
      testing on the study subjects whose results were negative on the DS screening and
      of healthy controls, limits further generalizibility of our findings. In
      addition, the findings from the 2 invasive techniques confirmed the existence of
      severe extracranial venous anomalies that significantly impaired normal blood
      outflow from the brain in this group of MS patients.

PMID- 24139137
TI  - Unusual patterns of recurrence in low grade gliomas.
AB  - Some of the more unusual patterns of recurrence in previously treated low grade
      gliomas are demonstrated. As treatment choices develop and life expectancy is
      prolonged, patterns of tumour recurrence are likely to change within such a
      heterogeneous group of tumours, including metastatic spread via cerebrospinal
      fluid pathways. 

PMID- 24139138
TI  - Apolipoprotein E-epsilon4 polymorphism and cognitive dysfunction after carotid
      endarterectomy.
AB  - Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit
      cognitive dysfunction (CD) 1 day and 1 month after CEA. The apolipoprotein E
      (apoE)-epsilon4 polymorphism has been previously identified as a robust
      independent risk factor for CD 1 month after CEA. We aimed to determine whether
      the apoE-epsilon4 polymorphism is also an independent risk factor for CD as early
      as 1 day after CEA and to confirm the previous findings at 1 month. Patients
      undergoing elective CEA (n=411) were enrolled with written informed consent in
      this follow-up observational study. CD was evaluated via an extensive
      neuropsychometric battery. apoE-epsilon4 carriers exhibited significantly more CD
      1 day (30.1% versus 17.9%, p=0.01) and 1 month (25.7% versus 9.8%, p=0.001) after
      CEA compared to non-carriers. Multivariate regression models were generated to
      determine independent predictors of CD. At 1 day, apoE-epsilon4 was significantly
      associated with higher risk of CD (odds ratio [OR]: 2.24 [95% confidence interval
      1.29-3.84], p=0.004), while statin use was significantly associated with lower
      risk (OR: 0.40 [0.24-0.67], p<0.001). At 1 month, apoE-epsilon4 was significantly
      associated with higher risk of CD (OR: 3.14 [1.53-6.38], p=0.002), while
      symptomatic status was significantly associated with lower risk (OR: 0.45 [0.20
      0.94], p=0.03). The apoE-epsilon4 polymorphism is an independent risk factor for
      CD as early as 1 day after CEA and is confirmed to be an independent risk factor
      for CD at 1 month as well.

PMID- 24139139
TI  - The use of routine outcome measures in two child and adolescent mental health
      services: a completed audit cycle.
AB  - BACKGROUND: Routine outcome measurement (ROM) is important for assessing the
      clinical effectiveness of health services and for monitoring patient outcomes.
      Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption
      of ROM in CAMHS has been supported by both national and local initiatives (such
      as government strategies, local commissioning policy, and research). METHODS:
      With the aim of assessing how these policies and initiatives may have influenced
      the uptake of ROM within two different CAMHS we report the findings of two case
      note audits: a baseline audit conducted in January 2011 and a re-audit conducted
      two years later in December 2012-February 2013. RESULTS: The findings show an
      increase in both the single and repeated use of outcome measures from the time of
      the original audit, with repeated use (baseline and follow-up) of the Health of
      the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing
      from 10% to 50% of cases. Re-audited case-notes contained more combined use of
      different outcome measures, with greater consensus on which measures to use.
      Outcome measures that were applicable across a wide range of clinical conditions
      were more likely to be used than symptom-specific measures, and measures that
      were completed by the clinician were found more often than measures completed by
      the service user. CONCLUSIONS: The findings show a substantial improvement in the
      use of outcome measures within CAMHS. These increases in use were found across
      different service organisations which were subject to different types of local
      service priorities and drivers.

PMID- 24139140
TI  - Enhanced implementation of low back pain guidelines in general practice: study
      protocol of a cluster randomised controlled trial.
AB  - BACKGROUND: Evidence-based clinical practice guidelines may improve treatment
      quality, but the uptake of guideline recommendations is often incomplete and
      slow. Recently new low back pain guidelines are being launched in Denmark. The
      guidelines are considered to reduce personal and public costs. The aim of this
      study is to evaluate whether a complex, multifaceted implementation strategy of
      the low back pain guidelines will reduce secondary care referral and improve
      patient outcomes compared to the usual simple implementation strategy.
      METHODS/DESIGN: In a two-armed cluster randomised trial, 100 general practices
      (clusters) and 2,700 patients aged 18 to 65 years from the North Denmark region
      will be included. Practices are randomly allocated 1:1 to a simple or a complex
      implementation strategy. Intervention practices will receive a complex
      implementation strategy, including guideline facilitator visits, stratification
      tools, and quality reports on low back pain treatment. Primary outcome is
      referral to secondary care. Secondary outcomes are pain, physical function,
      health-related quality of life, patient satisfaction with care and treatment
      outcome, employment status, and sick leave. Primary and secondary outcomes
      pertain to the patient level. Assessments of outcomes are blinded and follow the
      intention-to-treat principle. Additionally, a process assessment will evaluate
      the degree to which the intervention elements will be delivered as planned, as
      well as measure changes in beliefs and behaviours among general practitioners and
      patients. DISCUSSION: This study provides knowledge concerning the process and
      effect of an intervention to implement low back pain guidelines in general
      practice, and will provide insight on essential elements to include in future
      implementation strategies in general practice. TRIAL REGISTRATION: Registered as
      NCT01699256 on ClinicalTrials.gov.

PMID- 24139142
TI  - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma
      and skin changes) with cranial vault plasmocytoma and the role of surgery in its
      management: a case report.
AB  - INTRODUCTION: POEMS syndrome (an acronym of polyneuropathy, organomegaly,
      endocrinopathy, multiple myeloma and skin changes) is a paraneoplastic disorder
      related to an underlying plasma cell dyscrasia. The development of such a
      syndrome is rare and its association with calvarial plasmocytoma is even less
      common, with only two previous reported cases. We describe, in detail, an unusual
      presentation of cranial plasmocytoma associated with POEMS syndrome and briefly
      discuss the possible role of surgery in the management of this disease. CASE
      PRESENTATION: We present the case of a 45-year-old Caucasian man who was admitted
      to our department presenting with progressive weakness in his lower limbs,
      enlarged lymph nodes and a large mass on the scalp with intense bone erosion.
      POEMS criteria were present and pathological studies confirmed a Castleman's
      variant plasmocytoma. Clinical status improved noticeably after the excision of
      the plasmocytoma and the treatment was completed with radiotherapy and steroid
      pulse therapy. CONCLUSION: Cranial vault plasmocytoma and its association with
      POEMS syndrome are rare conditions with few previously reported cases. Although
      the role of surgery is not clearly defined in POEMS syndrome guidelines, the fact
      that there seems to be a better prognosis and clinical outcome when surgery is
      used as a part of the management in POEMS syndrome with cranial vault
      plasmocytoma is worth discussing.

PMID- 24139143
TI  - Is it smoking or related lifestyle variables that increase metabolic syndrome
      risk?
AB  - Metabolic syndrome is considered as mainly caused by a deleterious lifestyle
      (sedentarity and diet). That smoking contributes to metabolic syndrome had been
      suggested by several small studies and a meta-analysis. The interesting study by
      Slagter et al. published in BMC Medicine is the first very large study confirming
      this association in both genders, in all classes of body mass index, and in a
      dose-related manner. Surprisingly, smoking is even associated with increased
      abdominal fat. Rather than a direct causal effect of smoking, the reason for
      these associations is most probably the frequent presence of other lifestyle
      components in smokers. For example, physical inactivity and alcohol drinking are
      known to be more often present in smokers and could completely explain the
      observations of the Slagter et al. study. Unfortunately, these factors, already
      not properly checked in the first studies, were not assessed at all in the
      present one. However, as it is still on-going, we hope that other lifestyle
      factors will be included in future publications. 

PMID- 24139144
TI  - Relationship between efficiency and clinical effectiveness indicators in an
      adjusted model of resource consumption: a cross-sectional study.
AB  - BACKGROUND: Adjusted clinical groups (ACG(r)) have been widely used to adjust
      resource distribution; however, the relationship with effectiveness has been
      questioned. The purpose of the study was to measure the relationship between
      efficiency assessed by ACG(r) and a clinical effectiveness indicator in adults
      attended in Primary Health Care Centres (PHCs). METHODS:  RESEARCH DESIGN: cross
      sectional study. SUBJECTS: 196, 593 patients aged >14 years in 13 PHCs in
      Catalonia (Spain). MEASURES: Age, sex, PHC, basic care team (BCT), visits,
      episodes (diagnoses), and total direct costs of PHC care and co-morbidity as
      measured by ACG(r) indicators: Efficiency indices for costs, visits, and episodes
      (costs EI, visits EI, episodes EI); a complexity or risk index (RI); and
      effectiveness measured by a general synthetic index (SI). The relationship
      between EI, RI, and SI in each PHC and BCT was measured by multiple correlation
      coefficients (r). RESULTS: In total, 56 of the 106 defined ACG(r) were present in
      the study population, with five corresponding to 44.5% of the patients, 11 to
      68.0% of patients, and 30 present in less than 0.5% of the sample. The RI in each
      PHC ranged from 0.9 to 1.1. Costs, visits, and episodes had similar trends for
      efficiency in six PHCs. There was moderate correlation between costs EI and
      visits EI (r = 0.59). SI correlation with episodes EI and costs EI was moderate
      (r = 0.48 and r = -0.34, respectively) and was r = -0.14 for visits EI.
      Correlation between RI and SI was r = 0.29. CONCLUSIONS: The Efficiency and
      Effectiveness ACG(r) indicators permit a comparison of primary care processes
      between PHCs. Acceptable correlation exists between effectiveness and indicators
      of efficiency in episodes and costs.

PMID- 24139145
TI  - Differential changes in galactolipid and phospholipid species in soybean leaves
      and roots under nitrogen deficiency and after nodulation.
AB  - The availability of nitrogen (N) to plants has a profound impact on carbohydrate
      and protein metabolism, but little is known about its effect on membrane lipid
      species. This study examines the changes in galactolipid and phospholipid species
      in soybean as affected by the availability of N, either supplied to soil or
      obtained through Bradyrhizobium japonicum nodulation. When N was limited in soil,
      the content of galactolipids, monogalactosyldiacylglycerol (MGDG) and
      digalactosyldiacyglycerol (DGDG), decreased drastically in leaves, while a
      smaller decrease of DGDG was observed in roots. In both leaves and roots, the
      overall content of different phospholipid classes was largely unchanged by N
      limitation, although some individual phospholipid molecular species did display
      significant changes. Nodulation with Bradyrhizobium of soybean grown in N
      deficient soil resulted in a large increase in levels of plastidic lipid classes,
      MGDG, DGDG, and phosphatidylglycerol, along with smaller increases in non
      plastidic phospholipids in leaves. Nodulation also led to higher levels of
      phospholipids in roots without changes in root levels of MGDG and DGDG. Overall,
      N availability alters lipid content more in leaves than roots and more in
      galactolipids than phospholipids. Increased N availability leads to increased
      galactolipid accumulation in leaves, regardless of whether N is supplied from the
      soil or symbiotic fixation. 

PMID- 24139146
TI  - Anti-anhedonic effect of deep brain stimulation of the prefrontal cortex and the
      dopaminergic reward system in a genetic rat model of depression: an intracranial
      self-stimulation paradigm study.
AB  - BACKGROUND: One of the two core symptoms of major depression (MD), whether uni-
      or bipolar, is the inability to experience pleasure, suggested to be triggered by
      dysregulation within the brain reward system. In recent years, deep brain
      stimulation (DBS) has evolved as a potential tool to modulate pathological neural
      activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce
      depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal
      cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly,
      stimulation of vmPFC reduces anhedonia-like behavior in rats.
      OBJECTIVE/HYPOTHESIS: The present study addresses the question of whether the
      anti-anhedonic effect of vmPFC-DBS is mediated by the brain reward system.
      METHODS: Rats of the Flinders Sensitive Line (FSL), a validated genetic animal
      model of depression, and its controls, the Flinders Resistant Line (FRL), were
      stimulated in the vmPFC and tested in the forced swim test (FST), sucrose
      consumption test (SCT) and the intracranial self-stimulation (ICSS) paradigm. The
      curve-shift paradigm of ICSS was used in combination with vmPFC-DBS, d
      amphetamine and fluoxetine to quantify reward-facilitating or -attenuating
      treatment effects. RESULTS: Our findings support anti-depressive efficacy of
      vmPFC-DBS with respect to despair- and anhedonia-like behavior, as shown in the
      FST and SCT, respectively. However, DBS did not elicit reward-facilitating or
      reward-attenuating effects on ICSS behavior. CONCLUSION: These data suggest that
      it is unlikely that the anti-anhedonic effect of vmPFC-DBS depends on the
      mesolimbic dopaminergic reward system.

PMID- 24139147
TI  - Bilateral transcranial direct current stimulation over dorsolateral prefrontal
      cortex changes the drug-cued reactivity in the anterior cingulate cortex of crack
      cocaine addicts.
AB  - BACKGROUND: Patients addicted to crack-cocaine routinely have difficulty
      sustaining treatment, which could be related to dysfunctional cerebral activity
      that occurs in addiction. OBJECTIVE: To investigate the indirect
      electrophysiological effects of single transcranial direct current stimulation
      (tDCS) on cocaine-addicted brains. METHODS: The patients received either left
      cathodal/right anodal or sham stimulation over the DLPFC. The region of interest
      was the anterior cingulate cortex (ACC) during the N2 time window (200-350 ms).
      Event-related potentials in the ACC were measured during visual presentation of
      crack-related cues or neutral cues. RESULTS: Low-resolution brain electromagnetic
      tomography (LORETA) indicated that exposure to crack-related images led to
      increased activity in the ACC in the sham group, while the tDCS group showed
      decreased ACC activity after visualization of drug cues. CONCLUSION: Prefrontal
      tDCS specifically modulated the ACC response during exposure to visual drug cues
      in crack-cocaine users.

PMID- 24139148
TI  - [Satisfaction of professionals taking part in a project of telemonitoring in-home
      patients with chronic diseases (TELBIL-A project)].
AB  - OBJECTIVE: To analyze, through an on-line survey, the satisfaction of
      professionals (nurses/general practitioners) taking part in a project of
      telemonitoring in-home patients with chronic diseases (heart failure and/or
      pulmonary disease) with >=2 hospital admissions in the last year (TELBIL-A
      project). MATERIAL AND METHODS: An on-line questionnaire designed by the
      researchers (using "easy survey" application) was sent to professionals' email.
      It consisted of several items to assess satisfaction (Likert scale from 1
      strongly disagree, negative appreciation- to 5- strongly agree, positive
      appreciation-), age, number of years working in Primary Care, and an open
      question for comments. Data were analyzed using SPSS 18.0. RESULTS: We received
      responses from 50 out of 55 professionals (90.9%), of whom 94% were female, and
      68% aged >=40 years, with 90% working >5 years in Primary Care. They chose in 86%
      answer 4 or 5 for the item on overall satisfaction with the project, with the
      average score being 4.4. The means for the rest of questions were: 3.8 for
      interference with other professional daily tasks, 4.5 appreciating advantages in
      the management of patients, 4.2 for the feeling that patients are more involved
      in their own care, 3.9 for technological aspects, and 4.3 for recommending to a
      friend/relative. CONCLUSIONS: The study explores one aspect, satisfaction with
      the project, which is critical because of the association with the correct
      compliance and developing of the intervention. We found a high satisfaction of
      professionals involved with the TELBIL-A project.

PMID- 24139150
TI  - The impact of global sporting events.

PMID- 24139149
TI  - [A set of quality and safety indicators for hospitals of the "Agencia Valenciana
      de Salud"].
AB  - OBJECTIVES: To prepare a set of quality and safety indicators for Hospitals of
      the "Agencia Valenciana de Salud". MATERIAL AND METHODS: The qualitative
      technique Metaplan(r) was applied in order to gather proposals on sustainability
      and nursing. The catalogue of the "Spanish Society of Quality in Healthcare" was
      adopted as a starting point for clinical indicators. Using the Delphi technique,
      207 professionals were invited to participate in the selecting the most reliable
      and feasible indicators. Lastly, the resulting proposal was validated with the
      managers of 12 hospitals, taking into account the variability, objectivity,
      feasibility, reliability and sensitivity, of the indicators. RESULTS:
      Participation rates varied between 66.67% and 80.71%. Of the 159 initial
      indicators, 68 were prioritized and selected (21 economic or management
      indicators, 22 nursing indicators, and 25 clinical or hospital indicators). Three
      of them were common to all three categories and two did not match the specified
      criteria during the validation phase, thus obtaining a final catalogue of 63
      indicators. CONCLUSIONS: A set of quality and safety indicators for Hospitals was
      prepared. They are currently being monitored using the hospital information
      systems.

PMID- 24139151
TI  - Effect of single bout versus repeated bouts of stretching on muscle recovery
      following eccentric exercise.
AB  - OBJECTIVES: To analyze the effects of a single bout and repeated bouts of
      stretching on indirect markers of exercise-induced muscle damage. DESIGN: A
      randomized controlled clinical trial at a university human research laboratory
      was conducted. METHODS: Fifty-six untrained males were randomly divided into four
      groups. (I) a single stretching group underwent a single bout of stretching on
      the quadriceps muscle; (II) an eccentric exercised group underwent eccentric
      quadriceps muscle contractions until exhaustion; (III) an eccentric exercise
      group followed by a single bout of stretching; (IV) an eccentric exercised group
      submitted to repeated bouts of stretching performed immediately and 24, 48, and
      72 h post-exercise. Muscle stiffness, muscle soreness, maximal concentric peak
      torque, and plasma creatine kinase activity were assessed before exercise and 1,
      24, 48, 72, and 96 h post-exercise. RESULTS: All exercised groups showed
      significant reduction in maximal concentric peak torque and significant increases
      in muscle soreness, muscle stiffness, and plasma creatine kinase. There were no
      differences between these groups in all assessed variables, with the exception of
      markers of muscle stiffness, which were significantly lower in the eccentric
      exercise group followed by single or repeated bouts. The single stretching group
      showed no change in any assessed variables during the measurement period.
      CONCLUSIONS: Muscle stretching performed after exercise, either as single bout or
      as repeated bouts, does not influence the levels of the main markers of exercise
      induced muscle damage; however, repeated bouts of stretching performed during the
      days following exercise may have favorable effects on muscle stiffness.

PMID- 24139152
TI  - Choroidal melanocytosis evaluation with enhanced depth imaging optical coherence
      tomography.
AB  - OBJECTIVE: To assess eyes with unilateral choroidal melanocytosis using enhanced
      depth imaging (EDI) optical coherence tomography (OCT). DESIGN: Retrospective,
      observational case series. PARTICIPANTS: Fifteen patients with unilateral
      choroidal melanocytosis. METHODS: Each patient was evaluated with EDI-OCT, and
      comparison was made of involved versus uninvolved foveal retinal and choroidal
      layers. MAIN OUTCOME MEASURES: Enhanced depth imaging OCT features of choroidal
      melanocytosis. RESULTS: The mean patient age was 28 years (median, 23 years;
      range, 5-76 years). There were 9 male and 6 female patients. Best-corrected
      visual acuity ranged from 20/20 to 20/30. All patients had subfoveal involvement
      with choroidal melanocytosis. Associated features included dermal (n = 6),
      scleral (n = 9), iris (n = 3), and palate (n = 1) melanocytosis. Spectral domain
      EDI-OCT revealed normal inner retina (n = 15) and normal outer retina (n = 14).
      The only retinal abnormality was a defect in both the myoid zone and the
      ellipsoid junction (n = 1). The affected choroid showed smooth anterior contour
      (n = 15) and thinned or compressed choriocapillaris (n = 2), thinned (n = 3) or
      thickened (n = 3) medium vessels, and thinned large vessels (n = 2). The
      subfoveal choroid was a mean 23% thicker in the involved eye, with a mean
      thickness of 326.4 MUm (median, 326 MUm; range, 120-459 MUm) compared with 264.4
      MUm (median, 260 MUm; range, 94-462 MUm) in the uninvolved eye (P = 0.15). The
      choroidal perivascular interstitial tissue was 51% thicker in the study eye,
      enwrapping and silhouetting the medium and large vessels (P = 0.01). The ratio
      between the perivascular stromal tissue and the subfoveal choroidal thickness was
      66% in the study eye and 54% in the normal eye (P = 0.0001). Deep partial (n = 5)
      or complete (n = 2) tissue shadowing was noted. CONCLUSIONS: Enhanced depth
      imaging OCT revealed that choroidal melanocytosis shows increased subfoveal
      choroidal thickness with an apparent increase in the choroidal perivascular
      stromal tissue and minimal effect on the overlying retina.

PMID- 24139153
TI  - The effect of socioeconomic deprivation on corneal graft survival in the United
      Kingdom.
AB  - OBJECTIVE: To investigate the effect of socioeconomic deprivation on cornea graft
      survival in the United Kingdom. DESIGN: Retrospective cohort study. PARTICIPANTS:
      All the recipients (n = 13,644) undergoing their first penetrating keratoplasty
      (PK) registered on the United Kingdom Transplant Registry between April 1999 and
      March 2011 were included. METHODS: Data of patients' demographic details,
      indications, graft size, corneal vascularization, surgical complication,
      rejection episodes, and postoperative medication were collected at the time of
      surgery and 1, 2, and 5 years postoperatively. Patients with endophthalmitis were
      excluded from the study. Patients' home postcodes were used to determine the
      socioeconomic status using a well-validated deprivation index in the United
      Kingdom: A Classification of Residential Neighborhoods (ACORN). Kaplan-Meier
      survival and Cox proportional hazards regression were used to evaluate the
      influence of ACORN categories on 5-year graft survival, and the Bonferroni method
      was used to adjust for multiple comparisons. MAIN OUTCOME MEASURES: Patients'
      socioeconomic deprivation status and corneal graft failure. RESULTS: A total of
      13,644 patients received their first PK during the study periods. A total of 1685
      patients (13.36%) were lost to follow-up, leaving 11,821 patients (86.64%) for
      analysis. A total of 138 of the 11,821 patients (1.17%) developed
      endophthalmitis. The risk of graft failure within 5 years for the patients
      classified as hard-pressed was 1.3 times that of the least deprived (hazard
      ratio, 1.3; 95% confidence interval, 1.1-1.5; P = 0.003) after adjusting for
      confounding factors and indications. There were no statistically significant
      differences between the causes of graft failure and the level of deprivation (P =
      0.14). CONCLUSIONS: Patients classified as hard-pressed had an increased risk of
      graft failure within 5 years compared with the least deprived patients.

PMID- 24139154
TI  - Performance of the Moorfields motion displacement test for identifying eyes with
      glaucoma.
AB  - PURPOSE: The Moorfields Motion Displacement Test (MMDT; Enhanced Standard
      Threshold Algorithm [ESTA] version 1, London, UK) is a new 31-point
      suprathreshold test for visual field assessment using moving line stimuli
      displayed on a standard laptop computer. This study evaluated the diagnostic
      performance of the MMDT for discriminating between healthy eyes and eyes with
      glaucoma. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: Seventy
      eight subjects with glaucoma and 348 healthy subjects. METHODS: All participants
      underwent a standardized ophthalmologic examination, including the MMDT and
      Heidelberg Retina Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany)
      scanning of the optic disc. The diagnosis of glaucoma was based on clinical
      examination with glaucomatous optic neuropathy defined by the presence of
      neuroretinal rim thinning, notching or excavation of the cup, cup-to-disc
      asymmetry between eyes of 0.25 or more, nerve fiber layer thinning (focal or
      diffuse), or a combination thereof; and HRT-based Moorfields Regression Analysis
      (MRA) results of outside normal limits in any sector. Normal eyes were defined as
      clinically having healthy neuroretinal rims and an MRA analysis of within normal
      limits in all sectors. The MMDT used a Pandora response version of the ESTA
      without optical correction. Subjects with a false-positive response of 15% or
      more in MMDT were excluded. MAIN OUTCOME MEASURES: The performance of the global
      probability of true damage (global PTD) for diagnosing glaucoma was assessed by
      sensitivity, specificity, and area under the receiver operating characteristic
      curve (AUC). The global PTD was calculated as a sum of individual PTD values,
      ranging from 0% to 100% for all 31 visual locations, and was expressed as a
      quotient of 100. RESULTS: Seventy-eight subjects with glaucoma (mean age, 66.6+/
      13.1 years; male gender, 55.1%) and 348 healthy subjects (mean age, 55.2+/-9.2
      years; male gender, 35.3%) were analyzed. The AUC for the global PTD was 0.930
      (95% confidence interval, 0.893-0.967) for diagnosing glaucoma. At 85%
      specificity, the MMDT demonstrated a sensitivity of 88.5%. This decreased to
      83.3% at 95% specificity. At the global PTD cutoff point value of 2.0, the
      sensitivity was 85.9% and the specificity was 94.5%. CONCLUSIONS: The
      suprathreshold MMDT showed good diagnostic performance for diagnosing glaucoma
      when glaucoma was defined by a structural criterion.

PMID- 24139155
TI  - Prognostic factor analysis of vitrectomy for retinal detachment associated with
      myopic macular holes.
AB  - PURPOSE: To describe the anatomic and functional outcomes in a cohort of subjects
      undergoing vitrectomy for retinal detachment (RD) resulting from myopic macular
      hole (MH) and to analyze the prognostic and surgical factors predicting retinal
      reattachment and MH closure. DESIGN: Retrospective case series. PARTICIPANTS: All
      patients who underwent vitrectomy for RD resulting from myopic MH between 2000
      and 2009 at our center. METHODS: Case records were reviewed at 6 months after
      surgery. Retinal reattachment and complete anatomic success, defined as retinal
      reattachment with MH closure, were assessed. Multivariate logistic regression
      models, including age, gender, duration of symptoms, spherical equivalent
      refraction (SE), internal limiting membrane peeling, tamponade choice, and
      concurrent scleral buckling, were constructed to assess associations with
      covariates. MAIN OUTCOME MEASURES: Retinal reattachment and complete anatomic
      success (retinal reattachment with MH closure). RESULTS: In total, 114 subjects
      were analyzed. Most were women (n = 79 [69.3%]), and the mean age was 57.5+/-13.3
      years. The mean SE was -9.88+/-6.37 diopters. At 6 months, 98 subjects (86.0%)
      demonstrated retinal reattachment, of whom 93 subjects required only 1 operation.
      Complete anatomic success was achieved in 61 subjects (53.5%), of whom 55 needed
      only 1 operation. Subjects with retinal reattachment had better best-corrected
      visual acuity (BCVA; mean BCVA, 1.22+/-0.81 logarithm of the minimum angle of
      resolution [logMAR] units) than those without (mean BCVA, 1.98+/-1.26 logMAR
      units; P < 0.001), and subjects with complete anatomic success had better BCVA
      (mean BCVA, 1.05+/-0.87 logMAR units) than those without (mean BCVA, 1.62+/-0.87
      logMAR units; P < 0.001). In multivariate analyses, increasing age and the use of
      perfluoropropane (C3F8) tamponade were predictive of anatomic success (per 1-year
      increase: odds ratio [OR], 1.049; 95% confidence interval [CI], 1.002-1.099; P =
      0.04; and for tamponade: OR, 10.71; 95% CI, 1.08-106.29; P = 0.04). CONCLUSIONS:
      Vitrectomy is effective in the repair of RD resulting from MH in myopic eyes,
      with retinal reattachment achieved more frequently than MH closure. Retinal
      reattachment and MH closure are important for improving visual outcomes. Greater
      age at presentation and use of C3F8 are associated with a greater likelihood of
      anatomic success.

PMID- 24139156
TI  - Isotope fractionation and spectroscopic analysis as an evidence of Cr(VI)
      reduction during biosorption.
AB  - This work investigates the mechanisms behind Cr(VI) biosorption/reduction on
      three biomaterials (brewers draff, grape waste and synthetic humic acid). Coupled
      Cr isotope analysis with ICP-OES, XPS and SEM was tested as a novel approach to
      study the reduction of Cr(VI) by the biomaterials. The Cr(VI) biosorption process
      was accompanied with heavier Cr isotopes enrichment in the remaining Cr(VI)
      fraction. A significant fractionation of Cr stable isotopes was observed with no
      significant pH effect; delta(53)Cr of the remaining fraction ranged from 0.20/00
      to 1.90/00 while delta(53)Cr of the product (sorbed Cr) ranged from -1.20/00 to 
      2.80/00. The Rayleigh fractionation model fitted well the measured data and Cr
      isotope analysis provides thus an efficient tool to quantify Cr(VI) reduction by
      different biomaterials. In general, the sorption/reduction potential of the three
      studied biomaterials decreased in the following order: grape waste>humic
      acids>brewers draff.

PMID- 24139157
TI  - Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce
      apoptotic response in human liver cells (HepG2).
AB  - Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved
      understanding of their potential impact on human health. Previously, toxic
      effects of NiO NPs have been investigated, mainly on airway cells. However,
      information on effect of NiO NPs on human liver cells is largely lacking. In this
      study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity
      and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs
      exposure. Prepared NiO NPs were crystalline and spherical shaped with an average
      diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation
      in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced
      cell death drastically caused by NiO NPs exposure indicating that oxidative
      stress plays an important role in NiO NPs toxicity. Micronuclei induction,
      chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest
      that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR
      analysis showed that following the exposure of HepG2 cells to NiO NPs, the
      expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated
      whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated.
      Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells.
      To the best of our knowledge this is the first report demonstrating that NiO NPs
      caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely
      to be mediated through bax/bcl-2 pathway. This work warrants careful assessment
      of Ni NPs before their commercial and industrial applications.

PMID- 24139158
TI  - Gas-phase degradation of the herbicide ethalfluralin under atmospheric
      conditions.
AB  - The gas-phase degradation of ethalfluralin, N-ethyl-alpha,alpha,alpha-trifluoro-N
      (2-methylallyl)-2,6-dinitro-p-toluidine, a widely used herbicide, was
      investigated under atmospheric conditions at the large outdoor European
      simulation chamber (EUPHORE) in Valencia, Spain. The photolysis of ethalfluralin
      was investigated under solar radiation and the mean photolysis rate coefficient
      was determined: J(ethalfluralin)=(1.3+/-0.2)*10(-3) s(-1) (JNO2=8*10(-3) s(-1)).
      The rate coefficients for the reactions of hydroxyl radicals and ozone with
      ethalfluralin in the dark were also measured under atmospheric conditions using
      the relative rate and the absolute rate technique, respectively. The rate
      coefficients values for the reactions of kOH(ethalfluralin)=(3.5+/-0.9)*10(
      11)cm(3)molecule(-1)s(-1), and kO3(ethalfluralin)=(1.6+/-0.4)*10(-17) cm(3)
      molecule(-1) s(-1) were determined at 300+/-5 K and atmospheric pressure. The
      results show that removal of ethalfluralin from the atmosphere by reactions with
      OH radicals (tau ~ 4 h) or ozone (tau ~ 25 h) is slow compared to loss by
      photolysis. The available kinetic data suggest that the gas-phase tropospheric
      degradation of ethalfluralin will be controlled mainly by photolysis and provide
      an estimate for the tropospheric lifetime of approximately 12 min. The
      atmospheric implications of using ethalfluralin as a herbicide are discussed.

PMID- 24139159
TI  - Variation in concentration of perfluorooctanoic acid in methanol solutions during
      storage.
AB  - Perfluoroalkyl carboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA)
      have been widely recognized as persistent environmental contaminants. For
      accurate quantification of PFCAs, their stability in calibration solutions is
      important because they are criteria of quantification. To examine stability of
      PFCAs in methanol, we monitored PFOA and its related compounds around 4 years.
      Interestingly, perfluorooctanoate was varied randomly, and methyl
      perfluorooctanoate (MePFOA) and methyl formate were observed when
      perfluorooctanoate decreased. Moreover, no detection of both methyl esters was in
      methanol solutions immediately after preparation. In each of prepared methanol
      solution of perfluorohexanoic, perfluoroheptanoic, and perfluorononanoic acids,
      their corresponding methyl esters and methyl formate were observed. Furthermore,
      MePFOA was observed even in the solutions stored around 4 months and thereafter
      MePFOA increased with increase in methyl formate. Therefore, PFCAs including PFOA
      should be used immediately after preparation when methanol is used as a solvent.

PMID- 24139160
TI  - Extended filaments of bulking sludge sink in the floc layer with particulate
      substrate.
AB  - Recent studies have showed that particulate substrate has a positive effect on
      sludge settleability. This study was driven by the question of how the extended
      filaments disappeared when soluble substrate was switched to particulate
      substrate. A lab-scale aerobic completely stirred tank reactor was performed and
      evaluated for a period of two months. The results showed that extended filaments
      were quickly induced with soluble substrate. Total extended filament length of
      activated sludge decreased and sludge settleability was significantly improved
      after the soluble substrate was switch to particulate substrate. Due to the lack
      of hydrolysis products in the bulk liquid when particulate substrate was fed,
      extended filaments were forced to grow towards the inside of the flocs and
      finally sink in the floc layer. A physical model was proposed to explain the
      evolution of extended filaments caused by soluble substrate and cured by
      particulate substrate. 

PMID- 24139161
TI  - Reinstrumentation for rapid curve progression after implant removal following
      posterior instrumented fusion in adolescent idiopathic scoliosis: a case report.
AB  - BACKGROUND CONTEXT: Spinal implants are occasionally removed due to infection or
      soft tissue irritation secondary to prominence. Several studies have reported
      loss of scoliotic curve correction after implant removal. However, further review
      of the literature reveals no similar cases of rapid curve progression following
      implant removal in patients with adolescent idiopathic scoliosis (AIS)
      necessitating repeat posterior instrumented fusion. PURPOSE: To describe a 15
      year-old female AIS patient treated by posterior instrumented fusion, who
      developed unusual rapid coronal and sagittal curve progression after implant
      removal. STUDY DESIGN: Case report. METHODS: Retrospective case report. RESULTS:
      A 15-year-old female with Lenke type 1A AIS underwent a successful posterior
      spinal fusion with instrumentation. She initially had no complications after
      surgery, but three years after instrumentation, her implants were removed due to
      pain secondary to implant prominence. Fifteen months after removal, the main
      thoracic curve increased, compared with radiographs taken before removal, from 29
      degrees  to 57 degrees . This development required the patient to undergo
      additional surgery, which involved multiple osteotomies and posterior
      reinstrumentation. CONCLUSIONS: We must acknowledge that a remarkable amount of
      progression can occur rapidly following implant removal in scoliotic patients.
      Taking this into consideration,we need to carefully explain to patients that
      removal of their implants entails a risk of progressive deformity and that they
      need to follow-up with their physician after implant removal.

PMID- 24139162
TI  - Wall motion in the stenotic carotid artery: association with greyscale plaque
      characteristics, the degree of stenosis and cerebrovascular symptoms.
AB  - BACKGROUND: Systolic dilation of the atherosclerotic carotid artery depends on
      several factors including arterial compliance and the haemodynamic environment.
      The purpose of this study was to quantify wall motion in stenotic carotid
      arteries and investigate any associations with the ultrasound greyscale plaque
      characteristics, the degree of stenosis, and the presence of cerebrovascular
      symptoms. METHODS: Variations in the lumen diameters of 61 stenotic carotid
      arteries (stenosis range 10%-95%) from 47 patients were measured before the
      proximal shoulder of the atherosclerotic plaque using ultrasound image sequences
      over several cardiac cycles. Absolute and percentage diameter changes from
      diastole to systole were calculated and their relationship to the degree of
      stenosis, greyscale plaque characteristics, and the presence of ipsilateral
      hemispheric symptoms were studied. RESULTS: The mean absolute diameter change
      from diastole to systole was 0.45 mm (s.d. 0.17), and the mean percentage
      diameter change was 6.9% (s.d. 3.1%). Absolute and percentage diameter changes
      did not have a statistically significant relationship to the degree of stenosis,
      greyscale plaque characteristics, or the presence of ipsilateral hemispheric
      symptoms (p > 0.05). Parameters significantly correlated with the presence of
      symptoms were the degree of stenosis (p = 0.01), plaque greyscale median (p =
      0.02) and the plaque surface irregularity index (p = 0.02). CONCLUSIONS: Our
      study confirmed the degree of stenosis, plaque greyscale median and our surface
      irregularity index were significant predictors of symptoms, but found no
      significant correlation between diameter changes of stenosed carotid arteries and
      the presence of ipsilateral hemispheric symptoms.

PMID- 24139163
TI  - Are nursing home survey deficiencies higher in facilities with greater staff
      turnover.
AB  - OBJECTIVES: To examine CNA and licensed nurse (RN+LPN/LVN) turnover in relation
      to numbers of deficiencies in nursing homes. DESIGN: A secondary data analysis of
      information from the National Nursing Home Survey (NNHS) and contemporaneous data
      from the Online Survey, Certification and Reporting (OSCAR) database. Data were
      linked by facility as the unit of analysis to determine the relationship of CNA
      and licensed nurse turnover on nursing home deficiencies. SETTING: The 2004 NNHS
      used a multistage sampling strategy to generate a final sample of 1174 nursing
      homes, which represent 16,100 NHs in the United States. PARTICIPANTS: This study
      focused on the 1151 NNHS facilities with complete deficiency data. MEASUREMENTS:
      Turnover was defined as the total CNAs/licensed nurse full-time equivalents
      (FTEs) who left during the preceding 3 months (full- and part-time) divided by
      the total FTE. NHs with high turnover were defined as those with rates above the
      75th percentile (25.3% for CNA turnover and 17.9% for licensed nurse turnover)
      versus all other facilities. This study used selected OSCAR deficiencies from the
      Quality of Care, Quality of Life, and Resident Behavior categories, which are
      considered to be more closely related to nursing care. We defined NHs with high
      deficiencies as those with numbers of deficiencies above the 75th percentile
      versus all others. Using SUDAAN PROC RLOGIST, we included NNHS sampling design
      effects and examined associations of CNA/licensed nurse turnover with NH
      deficiencies, adjusting for staffing, skill mix, bed size, and ownership in
      binomial logistic regression models. RESULTS: High CNA turnover was associated
      with high numbers of Quality of Care (OR 1.53, 95% CI 1.10-2.13), Resident
      Behavior (OR 1.42, 95% CI 1.03-1.97) and total selected deficiencies (OR 1.54,
      95% CI 1.12-2.12). Licensed nurse turnover was significantly related to Quality
      of Care deficiencies (OR 2.06, 95% CI 1.50-2.82) and total selected deficiencies
      (OR 1.71, 95% CI 1.25-2.33). When both CNA turnover and licensed nurse turnover
      were included in the same model, high licensed nurse turnover was significantly
      associated with Quality of Care and total deficiencies, whereas CNA turnover was
      not associated with that category of deficiencies. CONCLUSION: Turnover in
      nursing homes for both licensed nurses and CNAs is associated with quality
      problems as measured by deficiencies.

PMID- 24139164
TI  - Melanocortin-4 receptor polymorphism rs17782313: association with obesity and
      eating in the absence of hunger in Chilean children.
AB  - OBJECTIVE: The aim of this study was to assess the association between
      melanocortin-4 receptor (MC4R) rs17782313 alleles with obesity and eating
      behavior scores in Chilean children. METHODS: A case-control study was conducted
      with 139 normal-weight and 238 obese children (ages 6-12 y). MC4R rs17782313
      genotypes were determined by quantitative-polymerase chain reaction allelic
      discrimination assays. Eating behavior scores were evaluated in a subset of
      participants using the Chilean version of the Child Eating Behavior Questionnaire
      (CEBQ). Additionally, five normal-weight C-allele carriers of rs17782313 were
      matched by sex, age, and body mass index (BMI) to five TT homozygous children to
      carry out the Eating in the Absence of Hunger (EAH) test. RESULTS: The frequency
      of the C-allele of MC4R rs17782313 was higher in the obese group than in the
      control group, without achieving statistical significance (odds ratio, 1.4; 95%
      confidence interval, 0.8-2.4; P = 0.16). CEBQ scores of "enjoyment of food" were
      higher (P = 0.04) and "satiety responsiveness" were lower (P = 0.02) in children
      with CC genotype than in those with TT genotype matched by sex, age, and BMI. In
      the EAH test, all five non-obese carriers of the C-allele (three CC and two CT)
      showed increased sweet snack consumption compared with five matched (by sex-age
      BMI) non-carriers after a preload meal, without achieving statistical
      significance (P = 0.06). CONCLUSION: MC4R polymorphism rs17782313 may contribute
      to childhood obesity, affecting enjoyment of food, satiety responsiveness, and
      possibly eating in the absence of hunger.

PMID- 24139165
TI  - Food labels: a critical assessment.
AB  - OBJECTIVE: Foods sold in packages have both front-of-package (FOP) labels and
      back-of-package (BOP) labels. The aim of this review is to determine the role
      they play in informing consumers as to the composition of foods in order to help
      select a healthy diet. METHODS: Recent literature was evaluated and findings
      combined with assessments made by the authors of food labels used in the United
      States and Canada. RESULTS: Research shows that most consumers have difficulty
      understanding the information provided by both FOP and BOP food labels used in
      the United States and Canada. Research has evaluated the merits of alternative
      designs. FOP labels should be based on a clear and simple design. They should
      present information on key nutrients (total fat, saturated fat, sugar, and sodium
      or salt) and also energy value. They should have color and words that indicate
      "high," "medium," and "low" levels. Labels can also state quantity per serving.
      The traffic light system is the best example of this design. An extra traffic
      light indicating the overall health value of the food should be added. A clearer
      BOP label also is needed. Implementation of a new food labeling system will
      probably be opposed by the food industry. More research is needed into which food
      label designs are most effective, especially for persuading consumers to select
      healthier food. CONCLUSIONS: Both FOP and BOP food labels used in the United
      States and Canada need to be redesigned using a traffic light system.

PMID- 24139166
TI  - Targeted sampling of cementum for recovery of nuclear DNA from human teeth and
      the impact of common decontamination measures.
AB  - BACKGROUND: Teeth are a valuable source of DNA for identification of fragmented
      and degraded human remains. While the value of dental pulp as a source of DNA is
      well established, the quantity and presentation of DNA in the hard dental tissues
      has not been extensively studied. Without this knowledge common decontamination,
      sampling and DNA extraction techniques may be suboptimal. Targeted sampling of
      specific dental tissues could maximise DNA profiling success, while minimising
      the need for laborious sampling protocols and DNA extraction techniques, thus
      improving workflows and efficiencies. We aimed to determine the location of
      cellular DNA in non-degraded human teeth to quantify the yield of nuclear DNA
      from cementum, the most accessible and easily sampled dental tissue, and to
      investigate the effect of a common decontamination method, treatment with sodium
      hypochlorite (bleach).We examined teeth histologically and subsequently
      quantified the yield of nuclear DNA from the cementum of 66 human third molar
      teeth. We also explored the effects of bleach (at varying concentrations and
      exposure times) on nuclear DNA within teeth, using histological and quantitative
      PCR methods. RESULTS: Histology confirmed the presence of nucleated cells within
      pulp and cementum, but not in dentine. Nuclear DNA yields from cementum varied
      substantially between individuals but all samples gave sufficient DNA (from as
      little as 20 mg of tissue) to produce full short tandem repeat (STR) profiles.
      Variation in yield between individuals was not influenced by chronological age or
      sex of the donor. Bleach treatment with solutions as dilute as 2.5% for as little
      as 1 min damaged the visible nuclear material and reduced DNA yields from
      cementum by an order of magnitude. CONCLUSIONS: Cementum is a valuable, and
      easily accessible, source of nuclear DNA from teeth, and may be a preferred
      source where large numbers of individuals need to be sampled quickly (for
      example, mass disaster victim identification) without the need for specialist
      equipment or from diseased and degraded teeth, where pulp is absent.
      Indiscriminant sampling and decontamination protocols applied to the outer
      surface of teeth can destroy this DNA, reducing the likelihood of successful STR
      typing results.

PMID- 24139167
TI  - 1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple
      target drugs for the potential treatment of neurodegenerative diseases.
AB  - Adenosine receptors and monoamine oxidases are drug targets for neurodegenerative
      diseases such as Parkinson's and Alzheimer's disease. In the present study we
      prepared a library of 55 mostly novel tetrahydropyrimido[2,1-f]purinediones with
      various substituents in the 1- and 3-position (1,3-dimethyl, 1,3-diethyl, 1,3
      dipropyl, 1-methyl-3-propargyl) and broad variation in the 9-position. A
      synthetic strategy to obtain 3-propargyl-substituted tetrahydropyrimido[2,1
      f]purinedione derivatives was developed. The new compounds were evaluated for
      their interaction with all four adenosine receptor subtypes and for their ability
      to inhibit monoamine oxidases (MAO). Introduction of mono- or di-chloro
      substituted phenyl, benzyl or phenethyl residues at N9 of the 1,3-dimethyl series
      led to the discovery of a novel class of potent MAO-B inhibitors, the most potent
      compound being 9-(3,4-dichlorobenzyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrimido[1,2
      f]purine-2,4(1H,3H)-dione (21g, IC(50) human MAO-B: 0.0629 MUM), which displayed
      high selectivity versus the other investigated targets. Potent dually active
      A1/A2A adenosine receptor antagonists were identified, for example, 9-benzyl-1
      methyl-3-propargyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)dione (19f,
      Ki, human receptors, A1: 0.249 MUM, A2A: 0.253 MUM). Several compounds showed
      triple-target inhibition, the best compound being 9-(2-methoxybenzyl)-1-methyl-3
      (prop-2-ynyl)-6,7,8,9-tetrahydro pyrimido [1,2-f]purine-2,4(1H,3H)-dione (19g, Ki
      A1: 0.605 MUM, Ki A2A: 0.417 MUM, IC(50) MAO-B: 1.80 MUM). Compounds inhibiting
      several different targets involved in neurodegeneration may exhibit additive or
      even synergistic effects in vivo.

PMID- 24139168
TI  - Bis-phosphonium salts of pyridoxine: the relationship between structure and
      antibacterial activity.
AB  - A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized
      and their antibacterial activities were evaluated in vitro. All compounds were
      inactive against gram-negative bacteria and exhibited the structure-dependent
      activity against gram-positive bacteria. The antibacterial activity enhanced with
      the increase in chain length at acetal carbon atom in the order n-Pr>Et>Me.
      Further increasing of length and branching of alkyl chain leads to the reduction
      of antibacterial activity. Replacement of the phenyl substituents at the
      phosphorus atoms in 5,6-bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]
      dioxino[4,5-c]pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl
      as well as chloride anions in the compound 1 with bromides (compound 14a)
      increased the activity against Staphylococcus aureus and Staphylococcus
      epidermidis up to 5 times (MICs=1-1.25 MUg/ml). But in practically all cases
      chemical modifications of compound 1 led to the increase of its toxicity for HEK
      293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]
      2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which
      demonstrated lower MIC values against S. aureus and S. epidermidis (1 MUg/ml) and
      lower cytotoxicity on HEK-293 cells (CC(50)=200 MUg/ml). Compound 10a had no
      significant mutagenic and genotoxic effects and was selected for further
      evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine
      were much more toxic than vancomycin.

PMID- 24139169
TI  - Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and
      selective inhibitors of PIM kinases.
AB  - A novel series of PIM inhibitors was derived from a combined effort in natural
      product-inspired library generation and screening. The novel pyrrolo[1,2
      a]pyrazinones initial hits are inhibitors of PIM isoforms with IC50 values in the
      low micromolar range. The application of a rational optimization strategy, guided
      by the determination of the crystal structure of the complex in the kinase domain
      of PIM1 with compound 1, led to the discovery of compound 15a, which is a potent
      PIM kinases inhibitor exhibiting excellent selectivity against a large panel of
      kinases, representative of each family. The synthesis, structure-activity
      relationship studies, and pharmacokinetic data of compounds from this inhibitor
      class are presented herein. Furthermore, the cellular activities including
      inhibition of cell growth and modulation of downstream targets are also
      described. 

PMID- 24139170
TI  - Observational skills assessment score: reliability in measuring amount and
      quality of use of the affected hand in unilateral cerebral palsy.
AB  - BACKGROUND: The Observational Skills Assessment Score (OSAS) measures amount and
      quality of use of the affected hand in children with unilateral Cerebral Palsy
      (CP) in bimanual activities and could therefore be a valuable addition to
      existing assessment tools. The OSAS consists of tasks that are age appropriate
      and require use of the affected hand. METHODS: To measure the agreement and
      reliability of the OSAS a convenience sample of two groups of 16 children with
      unilateral spastic CP (2.5-6 and 12-16 years old), performed age specific
      bimanual tasks in 2 measurement sessions. Three experienced raters took part in
      testing and 8 in scoring. Intra class correlation (ICC) values for intra- and
      inter-rater reliability, and the mean and standard deviation of the differences
      between measurements were calculated. For test-retest reliability beside ICC
      scores, Smallest Detectable Differences (SDDs) were calculated in 16 older and 10
      younger children. RESULTS: Generally, there seems to be good agreement between
      repeated measurements of the OSAS, as indicated by the small SDDs on most scales
      for quality of movement, compared to the range of their scales. This indicates
      potentially good sensitivity to change if used for patient evaluation purposes.
      The exceptions were the 'quality of reach' score for all tasks, and all quality
      scores for the stacking blocks task for the young children. As used in the
      present study, the OSAS has good discriminative capacity within patient
      populations as indicated by the high ICCs for most quality scores. Measuring the
      amount of use does not seem to be useful for either discrimination or evaluation.
      CONCLUSION: In general, the OSAS seems to be a reliable tool for assessing the
      quality of use of the affected hand in bimanual activities in younger and older
      children with unilateral CP. Some modifications may improve its usefulness and
      efficiency.

PMID- 24139171
TI  - Impact of the age of transfused red blood cells in the trauma population: a
      feasibility study.
AB  - Following injury, transfusion of red blood cells (RBCs) of increased storage
      duration has been associated with an increased morbidity and mortality.
      Prospective trials focusing on the impact of the storage age of RBCs in severely
      bleeding trauma patients have failed to accrue patients. This has been attributed
      to an inability to maintain a large inventory of fresh RBCs, and the difficulties
      in obtaining consent in severely bleeding trauma patients. To address these
      issues, we performed a prospective, observational pilot study to evaluate the
      feasibility of conducting a trial focusing on RBC age in patients following
      injury. METHODS: Patients with bleeding due to trauma were transfused RBCs <=10
      day old if they were ABO blood Type O (Group O) or were transfused the oldest
      RBCs in inventory if they were Type A, B or AB (Group A/B/AB). Clinicians were
      unaware of the specific age of the RBCs. RESULTS: 63 patients were analyzed
      (Group O, n=19; Group A/B/AB, n=44). Half of all patients had severe injuries ISS
      (median 22). The median admission base deficit was -5 mEq/L, and median total 24h
      use of RBC and FFP was 1.2 L. The age of RBCs transfused to Group O was
      significantly lower than for Group A/B/AB [median (IQR) A/B/AB=18.4 (11.4-25.4)
      days, and Group O=6 (4.2-7.8) days; p<0.001]. CONCLUSIONS: It appears feasible to
      conduct a RBC age trial in trauma patients using ABO blood type to construct
      comparative groups. Adequate RBC age separation between cohorts and reduced RBC
      age in the "young" group of patients who received units <=10 days old was
      achieved.

PMID- 24139172
TI  - Technical aspects of the syndesmotic screw and their effect on functional outcome
      following acute distal tibiofibular syndesmosis injury.
AB  - INTRODUCTION: Much of the currently available data on the technical aspects of
      syndesmotic screw placement are based upon biomechanical studies, using cadaveric
      legs with different testing protocols, and on surgeon preference. The primary aim
      of this study was to investigate the effect of the level of syndesmotic screw
      insertion on functional outcome. Further, the effects of number of cortices
      engaged, the diameter of the screw, use of a second syndesmotic screw and the
      timing of removal on functional outcome were tested. MATERIAL AND METHOD: All
      consecutive patients treated for an ankle fracture with concomitant acute distal
      tibiofibular syndesmotic injury that had a metallic syndesmotic screw placed,
      between 1 January 2004 and 31 December 2010, were included. Patient
      characteristics (i.e., age at injury and gender), fracture characteristics (i.e.,
      affected side, trauma mechanism, Weber fracture type and number of fractured
      malleoli), and surgical characteristics (i.e., level of screw placement, screw
      diameter, tri- or quadricortical placement, number of syndesmotic screws used and
      the timing of screw removal) were recorded. Outcome was measured using validated
      questionnaires, which were sent by post, and consisted of the American
      Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS), the Olerud
      Molander Ankle Score (OMAS) and a single question Visual Analog Scale (VAS) for
      patient satisfaction with outcome. RESULTS: During the 7-year study period, 122
      patients were treated for syndesmotic injury. A total of 93 patients (76%)
      returned the questionnaire. The median follow-up was 51 months. The outcome
      scoring systems showed an overall score for the entire group of 92 points for the
      AOFAS, 77 for the OMAS and 8.2 for the VAS. Outcome was statistically
      significantly influenced by the number of fractured malleoli, age, trauma
      mechanism and the level of screw insertion. CONCLUSION: Overall, the functional
      outcome of acute syndesmotic injuries treated with a syndesmotic screw was good
      and mainly influenced by patient and fracture characteristics. Most different
      technical aspects of placement appeared not to influence these results. Only
      screw placement above 41 mm negatively influenced outcome.

PMID- 24139174
TI  - Acceptability and perceived barriers and facilitators to creating a national
      research register to enable 'direct to patient' enrolment into research: the
      Scottish Health Research Register (SHARE).
AB  - BACKGROUND: Difficulties with recruitment pose a major, increasingly recognised
      challenge to the viability of research. We sought to explore whether a register
      of volunteers interested in research participation, with data linkage to
      electronic health records to identify suitable research participants, would prove
      acceptable to healthcare staff, patients and researchers. METHODS: We undertook a
      qualitative study in which a maximum variation sampling approach was adopted.
      Focus groups and interviews were conducted with patients, general practitioners
      (GP), practice managers and health service researchers in two Scottish health
      boards. Analysis was primarily thematic to identify a range of issues and
      concerns for all stakeholder groups. RESULTS: The concept of a national research
      register was, in general, acceptable to all stakeholder groups and was widely
      regarded as beneficial for research and for society. Patients, however,
      highlighted a number of conditions which should be met in the design of a
      register to expedite confidence and facilitate recruitment. They also gave their
      perceptions on how a register should operate and be promoted, favouring a range
      of media. GPs and practice managers were primarily concerned with the security
      and confidentiality of patient data and the impact a register may have on their
      workload. Researchers were supportive of the initiative seeing advantages in more
      rapid access to a wider pool of patients. They did raise concerns that GPs may be
      able to block access to personal patient data held in general practice clinical
      systems and that the register may not be representative of the whole population.
      CONCLUSIONS: This work suggests that patients, healthcare staff and researchers
      have a favourable view of the potential benefits of a national register to
      identify people who are potentially eligible and willing to participate in health
      related research. It has highlighted a number of issues for the developers to
      incorporate in the design of research registers.

PMID- 24139176
TI  - A cross-sectional examination of school characteristics associated with
      overweight and obesity among grade 1 to 4 students.
AB  - BACKGROUND: Excessive weight gain among youth is an ongoing public health
      concern. Despite evidence linking both policies and the built environment to
      adolescent and adult overweight, the association between health policies or the
      built environment and overweight are often overlooked in research with children.
      The purpose of this study was to examine if school-based physical activity
      policies and the built environment surrounding a school are associated with
      weight status among children. METHODS: Objectively measured height and weight
      data were available for 2,331 grade 1 to 4 students (aged 6 to 9 years) attending
      30 elementary schools in Ontario, Canada. Student-level data were collected using
      parent reports and the PLAY-On questionnaire administered to students by study
      nurses. School-level policy data were collected from school administrators using
      the Physical Activity Module of the Healthy School Planner tool, and built
      environment data were provided by the Enhanced Points of Interest data resource.
      Multi-level logistic regression models were used to examine the school- and
      student-level characteristics associated with the odds of a student being
      overweight or obese. RESULTS: There was significant between-school random
      variation in the odds of a student being overweight [sigma2(MU0) = 0.274(0.106),
      p < 0.001], but not for being obese [sigma2(MU0) = 0.115(0.089)]. If a student
      attended a school that provided student access to a variety of facilities on and
      off school grounds during school hours or supported active transportation to and
      from school, he/she was less likely to overweight than a similar student
      attending a school without these policies. Characteristics of the built
      environment were not associated with overweight or obesity among this large cross
      sectional sample of children. CONCLUSIONS: This new evidence suggests that it may
      be wise to target obesity prevention efforts to schools that do not provide
      student access to recreation facilities during school hours or schools that do
      not support active transportation for students. Future research should evaluate
      if school-based overweight and obesity prevention programming might be improved
      if interventions selectively targeted the school characteristics that are putting
      students at the greatest risk.

PMID- 24139177
TI  - L233P mutation of the Tax protein strongly correlated with leukemogenicity of
      bovine leukemia virus.
AB  - The bovine leukemia virus (BLV) Tax protein is believed to play a crucial role in
      leukemogenesis by the virus. BLV usually causes asymptomatic infections in
      cattle, but only one-third develop persistent lymphocytosis that rarely progress
      after a long incubation period to lymphoid tumors, namely enzootic bovine
      leucosis (EBL). In the present study, we demonstrated that the BLV tax genes
      could be divided into two alleles and developed multiplex PCR detecting an L233P
      mutation of the Tax protein. Then, in order to define the relationship between
      the Tax protein and leukemogenicity, we examined 360 tumor samples randomly
      collected from dairy or breeding cattle in Japan, of which Tax proteins were
      categorized, for age at the time of diagnosis of EBL. The ages of 288 animals
      (80.0%) associated with L233-Tax and those of 70 animals (19.4%) with P233-Tax
      individually followed log-normal distributions. Only the two earliest cases
      (0.6%) with L233-Tax disobeyed the log-normal distribution. These findings
      suggest that the animals affected by EBL were infected with the virus at a
      particular point in life, probably less than a few months after birth. Median age
      of those with P233-Tax was 22 months older than that with L233-Tax and geometric
      means exhibited a significant difference (P<0.01). It is also quite unlikely that
      viruses carrying the particular Tax protein infect older cattle. Here, we
      conclude that BLV could be divided into two categories on the basis of amino acid
      at position 233 of the Tax protein, which strongly correlated with
      leukemogenicity. 

PMID- 24139178
TI  - The effect of bacterial dose and foal age at challenge on Rhodococcus equi
      infection.
AB  - While Rhodococcus equi remains the most common cause of subacute or chronic
      granulomatous bronchopneumonia in foals, development of a relevant model to study
      R. equi infection has proven difficult. The objective of this study was to
      identify a challenge dose of R. equi that resulted in slow progressive disease,
      spontaneous regression of lung lesions and age-dependent susceptibility. Foals
      less than one-week of age were challenged intratracheally using either 10(6),
      10(5), 10(4), 10(3) or 10(2) cfu of R. equi. Two doses (10(3) cfu and 10(5) cfu)
      were used to challenge 2 and 3-week-old, and 3 and 6-week-old foals,
      respectively. Physical examination, thoracic ultrasound and blood work were
      performed. Foals were euthanized at the end of the study or when clinical signs
      of pneumonia developed. All foals were necropsied and their lung lesions scored.
      Foals challenged with low concentrations of R. equi developed slow progressive
      pneumonia and approximately 50% of the foals recovered spontaneously. Likewise,
      macroscopic (>1cm diameter) pyogranulomatous lesions were only observed when low
      doses of R. equi were used. Clinical pneumonia was not seen after low dose
      challenge in the 3-week-old foals or in the 6-week-old foals. This study
      demonstrates that the use of low doses of R. equi to challenge neonatal foals
      provides an improved model for studying this disease. Furthermore, susceptibility
      to R. equi infection was shown to diminish early in the foal's life, as has been
      reported in the field.

PMID- 24139180
TI  - Curvularia lunata: a rare cause of black-grain eumycetoma.
AB  - Curvularia lunata is a dematiaceous fungus that rarely causes cutaneous
      infections in immunocompetent humans. We describe a case of mycetoma pedis caused
      by Curvularia lunata in a 50-year-old woman from a rural farming community who
      had prolonged morbidity due to diagnostic delay. She improved with antifungal
      therapy, showing a satisfactory clinical response after 12 months of treatment.

PMID- 24139179
TI  - Antimicrobial peptide beta-defensin-1 expression is upregulated in Alzheimer's
      brain.
AB  - BACKGROUND: The human beta-defensins (hBDs) are a highly conserved family of
      cationic antimicrobial and immunomodulatory peptides expressed primarily by
      epithelial cells in response to invasion by bacteria, fungi and some viruses. To
      date, the most studied members of this family of peptides are hBD-1, -2, and -3.
      Expression of hBD-1 and -2 has been demonstrated previously in cultured microglia
      and astrocytes of both mouse and human brain. Unlike inducible hBD-2 and -3, hBD
      1 is constitutively expressed and is not generally upregulated by proinflammatory
      factors. In this study, we investigated whether hBDs, as active components of the
      innate immune response, are affected by pathological events in the Alzheimer's
      disease (AD) brain. We assessed the expression of hBD-1, -2, and -3 in tissue
      obtained at autopsy from AD and age-matched control brains. METHODS: Fixed and
      frozen choroid plexus and the CA1 region of the hippocampus were obtained at
      autopsy from individuals diagnosed with AD, or from age-matched control brains
      without diagnosed neurodegenerative disease. Histopathologically diagnosed AD
      brain tissue was obtained for our study. Immunocytochemical analysis was
      performed using affinity purified polyclonal antibodies directed against hBD-1, 
      2, or -3. TaqMan gene expression assays were used to quantify the mRNA of hBD-1, 
      2, and -3 in the choroid plexus and hippocampus. Immunocytochemical detection of
      iron deposits was achieved using a modified Perl's stain for redox-active iron.
      In vitro experiments were performed on human primary oral epithelial cells to
      model the human choroid plexus epithelial response to ferric chloride. Cells were
      then exposed to ferric chloride added to selected wells at 0, 1, or 10 mM
      concentrations for 24 h at 37 degrees C. Total mRNA was isolated to quantify hBD
      1 mRNA expression by RTqPCR. RESULTS: hBD-1 peptide is apparent in astrocytes of
      the AD hippocampus and hippocampal neurons, notably within granulovacuolar
      degeneration structures (GVD). A higher level of hBD-1 was also seen in the
      choroid plexus of AD brain in comparison to age-matched control tissue. Increased
      expression of hBD-1 mRNA was observed only in the choroid plexus of the AD brain
      when compared to expression level in age-matched control brain. Redox-active iron
      was also elevated in the AD choroid plexus and in vitro addition of Fe+3Cl3 to
      cultured epithelial cells induced hBD-1 mRNA expression. CONCLUSIONS: Our
      findings suggest interplay between hBD-1 and neuroimmunological responses in AD,
      marked by microglial and astrocytic activation, and increased expression of the
      peptide within the choroid plexus and accumulation within GVD. As a
      constitutively expressed component of the innate immune system, we propose that
      hBD-1 may be of considerable importance early in the disease process. We also
      demonstrate that increased iron deposition in AD may contribute to the elevated
      expression of hBD-1 within the choroid plexus. These findings represent a
      potentially important etiological aspect of Alzheimer's disease neuropathology
      not previously reported.

PMID- 24139181
TI  - Study on fungi in archives of offices, with a particular focus on Stachybotrys
      chartarum.
AB  - OBJECTIVE: This study aimed at evaluating fungi in archives of different offices
      in Sari city the capital of Mazandaran, a northern province of Iran, with a
      particular focus on Stachybotrys chartarum. MATERIALS AND METHODS: The samples
      were collected from twenty archives of offices and controls (n=7) using a SKC
      single-stage impactor which draws air at 20L/min (100L) and impacts the sampled
      material onto Petri dishes containing malt extract agar (MEA) (n=22) and also
      cellulose agar (CA) (n=22). Surface samples were also collected by pressing a
      sterile cotton swab on different areas of archives and cultured on MEA and CA.
      The grown fungi were identified by standard mycological techniques. The counted
      fungal colonies were converted to CFUs per cubic meter. RESULTS: In indoor air of
      archives, Cladosporium spp (25.1%), Aspergillus spp (22.9%) and Penicillium spp
      (22.9%) had the most frequencies. Stachybotrys chartarum (7.9%) was the fourth
      most common fungus isolated from the surface samples. Cladosporium spp had the
      highest total CFU concentration in indoor air of archive samples (1227/m(3)).
      Stachybotrys chartarum was recovered from surface collected samples of 4 archives
      of offices on CA. Out of the 22 rooms of archives, 45.4%, 45.4% and 9.1% had
      concentration level < 170 CFU/m(3), > 170 < 560 CFU/m(3) and > 560 < 1000
      CFU/m(3), respectively. CONCLUSION: The results of our study have shown the high
      concentration levels of airborne fungi in some archives of offices that might put
      the workers at risk from respiratory diseases.

PMID- 24139182
TI  - Antimicrobial activity of saquayamycins produced by Streptomyces spp. PAL114
      isolated from a Saharan soil.
AB  - A new strain of actinomycete designated PAL114, producing antimicrobial
      compounds, was isolated from a Saharan soil in Ghardaia, Algeria. Morphological
      and chemical studies showed that this strain belonged to the genus Streptomyces.
      Two bioactive compounds, named P41A and P41B, were extracted by dichloromethane
      from the cell-free supernatant broth of strain PAL114 and were purified by HPLC.
      Minimum inhibitory concentrations of the pure antibiotics were determined against
      yeasts, filamentous fungi and bacteria, most of which are pathogenic or toxigenic
      for human and multiresistant to antibiotics. The strongest activities were
      observed against Candida albicans M3 and Bacillus subtilis ATCC 6633. The
      chemical structures of the compounds were determined by spectroscopic analysis of
      UV-visible and 1H and 13C NMR spectra and spectrometric analysis of mass
      spectrum. The compounds P41A and P41B were identified as saquayamycins A and C,
      respectively. These compounds belong to the aquayamycin-group antibiotics, which
      are known in the literature for their anticancer and antibacterial activities.

PMID- 24139183
TI  - Interest of contrast-enhanced sonography to identify focal nodular hyperplasia
      with sinusoidal dilatation.
AB  - BACKGROUND AND AIMS: Focal nodular hyperplasia with major sinusoidal dilatation
      (FNH-sd) is a misleading entity, with some features resembling inflammatory
      hepatocellular adenoma (HCA). We aimed to assess the performance of contrast
      enhanced ultrasound (CEUS) for the diagnosis of FNH-sd. METHODS: Four
      histologically proven FNH-sd nodules in four patients were investigated with both
      MRI and CEUS imaging. Sinusoidal dilatation was focally visible in all cases in
      histology. RESULTS: In MRI, in all the four cases, lesions were hypervascular in
      arterial phase, with high intensity in T2-weighted sequence imaging and
      persistent enhancement in the delayed gadolinium-enhanced phase. These MRI
      features were more indicative of HCA than FNH. On the other hand, CEUS showed a
      very specific centrifugal filling followed by a strong, homogeneous enhancement
      of the whole lesion. CONCLUSION: CEUS seems to be an essential step for the
      diagnosis of non-typical FNH, such as FNH-sd. This small series highlights the
      interest of performing both CEUS and MRI for the diagnosis of atypical focal
      liver lesions, such as FNH-sd.

PMID- 24139185
TI  - AMP v Myriad: the Supreme Court gives a win to personalized medicine.
AB  - The guest editorial provides perspective to the decision by the Supreme Court of
      the United States in the case of Association for Molecular Pathology v Myriad
      Genetics, Inc. 

PMID- 24139186
TI  - Depression in Aboriginal men in central Australia: adaptation of the Patient
      Health Questionnaire 9.
AB  - BACKGROUND: While Indigenous Australians are believed to be at a high risk of
      psychological illness, few screening instruments have been designed to accurately
      measure this burden. Rather than simply transposing western labels of symptoms,
      this paper describes the process by which a screening tool for depression was
      specifically adapted for use across multiple Indigenous Australian communities.
      METHOD: Potential depression screening instruments were identified and
      interrogated according to a set of pre-defined criteria. A structured process was
      then developed which relied on the expertise of five focus groups comprising of
      members from primary Indigenous language groups in central Australia. First,
      focus group participants were asked to review and select a screening measure for
      adaptation. Bi-lingual experts then translated and back translated the language
      within the selected measure. Focus group participants re-visited the difficult
      items, explored their meaning and identified potential ways to achieve
      equivalence of meaning. RESULTS: All five focus groups independently selected the
      Primary Health Questionnaire 9, several key conceptual differences were exposed,
      largely related to the construction of hopelessness. Together with translated
      versions of each instrument for each of the five languages, a single, simplified
      English version for use across heterogeneous settings was negotiated.
      Importantly, the 'code' and specific conceptually equivalent words that could be
      used for other Indigenous language groups were also developed. CONCLUSIONS: The
      extensive process of adaptation used in this study has demonstrated that within
      the context of Indigenous Australian communities, across multiple language
      groups, where English is often a third or fourth language, conceptual and
      linguistic equivalence of psychological constructs can be negotiated. A
      validation study is now required to assess the adapted instrument's potential for
      measuring the burden of disease across all Indigenous Australian populations.

PMID- 24139187
TI  - Transcriptional profiling in infectious diseases: ready for prime time?
AB  - Blood represents a reservoir and a migration compartment of cells of the immune
      system. Traditional microbiologic diagnostic tests relied on laboratory
      identification of the pathogen causing the infection. However, this approach is
      less than optimal for a variety of reasons: pathogen's slow growth, resistance to
      cultivation in vitro or insufficient proof to establish causality when a pathogen
      is identified. An alternative approach to the pathogen-detection strategy is
      based on a comprehensive analysis of the host response to the infection by
      analysis of blood leukocytes gene expression profiles. This strategy has been
      successfully applied to distinguish and classify children and adults with acute
      infections caused by different pathogens. Molecular distance to health (MDTH) is
      a genomic score that measures the global transcriptional perturbation in each
      individual patient compared to healthy controls. Studies indicate that MDTH is a
      promising biomarker to help classifying patients according to clinical severity.

PMID- 24139188
TI  - Advances towards the prevention of meningococcal B disease: a multidimensional
      story.
AB  - Whilst much progress has been made in reducing the burden of bacterial meningitis
      and septicaemia through vaccination, endemic serogroup B meningococcal (MenB)
      disease has remained problematic. Polysaccharide-protein conjugate vaccines are
      now available to protect against Haemophilus influenzae type b, Neisseria
      meningitidis serogroups A, C, Y and W and thirteen serotypes of Streptococcus
      pneumoniae, but this approach has not been used for MenB. Instead efforts have
      been made to identify protein antigens which, when used in vaccines, will prevent
      MenB infection and possibly disease due to other serogroups too. The first such
      vaccine has recently been licensed. 

PMID- 24139189
TI  - Ureaplasma--Are you sitting comfortably?
AB  - The role of Ureaplasma spp. in human disease has been controversial, as these
      bacteria are commonly isolated as part of the normal genital tract flora.
      Ureaplasma has been shown to have a causal role in urogenital infections and is
      associated with significant foetal and neonatal morbidity and mortality when
      infection occurs during the perinatal period. Although rare, invasive Ureaplasma
      infection (meningitis, renal abscess, mediastinitis and arthritis) has also been
      reported in both adults and children. This review outlines the unique
      microbiological features and various clinical presentations of Ureaplasma
      infection. It also discusses the treatment options, which in the neonatal period
      can be particularly challenging. 

PMID- 24139190
TI  - Eliminating mother to child transmission of HIV-1 and keeping mothers alive:
      recent progress.
AB  - The elimination of new HIV infections in infants and children is part of a
      broader global commitment by the United Nations. Prevention of Mother to Child
      transmission (PMTCT) programmes have prevented 350,000 new HIV infections with
      the use of antiretroviral therapy (ARVs) for pregnant women who are HIV infected,
      and the majority of these gains were in sub-Saharan Africa. Coverage of PMTCT
      programmes throughout Africa is variable resulting in many women not having
      access to the appropriate interventions in the antenatal care setting to prevent
      vertical transmission. The global elimination target requires a 90% reduction of
      new child infections and to decrease MTCT to <5% which potentially can be
      achieved utilising the four pronged approach proposed by the World Health
      Organization. Family planning messages and provision of contraception methods to
      avoid unplanned pregnancies are shown to be more effective than HIV Counselling
      and Testing [HCT] and single dose Nevirapine in averting transmission of
      perinatal HIV infection. Child survival goes beyond HIV-free survival and safe
      breastfeeding prevents 13% of deaths under 5 years of age rendering it essential
      to reduce under-5 mortality. Health systems strengthening to deliver more complex
      regimens either for prevention purposes or the mothers own health is an important
      part of a broader continuum of interventions which will depend on the effective
      delivery of current treatment modalities, development of new prevention
      interventions including a vaccine, and include prevention of unplanned
      pregnancies and primary prevention of HIV infections in the mother.

PMID- 24139192
TI  - Foreword. Polymorphic ventricular tachycardia (PMVT).

PMID- 24139191
TI  - Study protocol for reducing childbirth fear: a midwife-led psycho-education
      intervention.
AB  - BACKGROUND: Childbirth fear has received considerable attention in Scandinavian
      countries, and the United Kingdom, but not in Australia. For first-time mothers,
      fear is often linked to a perceived lack of control and disbelief in the body's
      ability to give birth safely, whereas multiparous women may be fearful as a
      result of previous negative and/or traumatic birth experiences. There have been
      few well-designed intervention studies that test interventions to address women's
      childbirth fear, support normal birth, and diminish the possibility of a negative
      birth experience. METHODS/DESIGN: Pregnant women in their second trimester of
      pregnancy will be recruited and screened from antenatal clinics in Queensland,
      Australia. Women reporting high childbirth fear will be randomly allocated to the
      intervention or control group. The psycho-educational intervention is offered by
      midwives over the telephone at 24 and 34 weeks of pregnancy. The intervention
      aims to review birth expectations, work through distressing elements of
      childbirth, discuss strategies to develop support networks, affirm that negative
      childbirth events can be managed and develop a birth plan. Women in the control
      group will receive standard care offered by the public funded maternity services
      in Australia. All women will receive an information booklet on childbirth
      choices. Data will be collected at recruitment during the second trimester, 36
      weeks of pregnancy, and 4-6 weeks after birth. DISCUSSION: This study aims to
      test the efficacy of a brief, midwife-led psycho-education counselling (known as
      BELIEF: Birth Emotions - Looking to Improve Expectant Fear) to reduce women's
      childbirth fear. 1) Relative to controls, women receiving BELIEF will report
      lower levels of childbirth fear at term; 2) less decisional conflict; 3) less
      depressive symptoms; 4) better childbirth self-efficacy; and 5) improved health
      and obstetric outcomes. TRIAL REGISTRATION: Australian New Zealand Controlled
      Trials Registry ACTRN12612000526875.

PMID- 24139193
TI  - Polymorphic ventricular tachycardia-part I: structural heart disease and acquired
      causes.
AB  - Polymorphic ventricular tachycardia (PMVT) is an unusual ventricular
      tachyarrhythmia. Perhaps its most unique characteristic is a continuously
      evolving QRS morphology. Although the most common substrate for PMVT is
      structural heart disease, the prevalence of sudden cardiac death in the
      population without structural heart disease is even greater, and the absence of a
      myocardial substrate would suggest that PMVT is the anticipated cause of sudden
      cardiac death in this population as well. Mechanistically, PMVT is distinct from
      ventricular fibrillation. It appears to be a condition of abnormal repolarization
      and resultant cellular heterogeneities, and the principles of triggering and
      reentry have been demonstrated to govern its initiation and maintenance. The
      "channelopathies"-a growing category of inherited or acquired conditions that
      predispose to PMVT and sudden cardiac death-present a fascinating challenge with
      potentially dire consequences as there are few indicators of their existence
      except for subtle, if any, electrocardiographic changes. The ever-expanding
      number of pharmaceuticals that affect ion channel function further magnifies this
      risk. 

PMID- 24139194
TI  - Craniofacial neurofibromatosis: treatment of the midface deformity.
AB  - Craniofacial Neurofibromatosis is a benign but devastating disease. While the
      most common location of facial involvement is the orbito-temporal region,
      patients often present with significant mid-face deformities. We reviewed our
      experience with Craniofacial Neurofibromatosis from June 1981 to June 2011 and
      included patients with midface soft tissue deformities defined as gross
      alteration of nasal or upper lip symmetry. Data reviewed included the medical
      records and photobank. Over 30 years, 52 patients presented to and underwent
      surgical management for Craniofacial Neurofibromatosis at the Chang Gung
      Craniofacial Center. 23 patients (43%) demonstrated gross mid-facial deformities
      at initial evaluation. 55% of patients with lip deformities and 28% of patients
      with nasal deformities demonstrated no direct tumour involvement. The respective
      deformity was solely due to secondary gravitational effects from neurofibromas of
      the cheek subunit. Primary tumour infiltration of the nasal and/or labial
      subunits was treated with excision followed by various methods of reconstruction
      including lower lateral cartilage repositioning, forehead flaps, free flaps,
      and/or oral commissure suspension. Soft tissue deformities of the midface are
      very common in patients with Craniofacial Neurofibromatosis and profoundly affect
      overall aesthetic outcomes. Distinguishing primary from secondary involvement of
      the midface assists in surgical decision making. 

PMID- 24139196
TI  - The Longitudinal Youth at Risk Study (LYRIKS)--an Asian UHR perspective.
AB  - Numerous studies have been published on the psychosis prodrome and have explored
      a wide array of its many aspects. However, the set of risk factors identified by
      these various efforts is not homogenous across studies. This could be due to
      unique population factors or relatively small sample sizes. Only few studies were
      conducted on Asian populations, whose socio-cultural characteristics differ - in
      some cases remarkably - from those in western populations. Singapore is a highly
      dense city-state in South-east Asia, with low rates of substance abuse. The
      Longitudinal Youth at Risk Study (LYRIKS) commenced in Singapore in 2008,
      designed to comprehensively assess a group of ultra high risk (UHR) individuals
      and identify clinical, social, neuropsychological and biological risk factors
      unique to the local population. 173 UHR individuals were recruited from this
      single-site study over 4 years. Here, we detail aspects of the study methodology
      and report on the baseline social and clinical characteristics of the sample
      population. 78% of the UHR sample suffered from a psychiatric disorder, with
      Major Depressive Disorder present in more than half of the sample. The mean
      Global Assessment of Functioning (GAF) score was 57.4, which indicated a moderate
      level of impairment. Although the recruited sample did not differ significantly
      by social and clinical characteristics when compared to previously published
      reports, the conversion rate to psychosis was 3.5% (n=6) at 6 months. Follow-up
      measures are currently underway to assess longitudinal incidence of psychosis and
      impact of risk factors on cognition, functioning and remission.

PMID- 24139197
TI  - Longitudinal design for sonographic measurement of median nerve swelling with
      controlled exposure to physical work using an animal model.
AB  - In the study described here, we examined the feasibility of a longitudinal design
      to measure sonographically swelling of the median nerve caused by controlled
      exposure to a work task and to evaluate the relationship of changes in morphology
      to diagnostic standards. Fifteen macaques, Macaca fascicularis, pinched a lever
      in various wrist positions at a self-regulated pace (8 h/d, 5 d/wk, 18-20 wk).
      Nerve conduction velocity (NCV) and cross-sectional area (CSA) were measured
      every 2 wk from baseline through working and a 6-wk recovery. Trending across all
      subjects revealed that NCV slowed and CSA at the carpal tunnel increased in the
      working arm, whereas no changes were observed in CSA either at the forearm or for
      any measure in the non-working arm. There was a small negative correlation
      between NCV and CSA in the working arm. This study provides validation that
      swelling can be observed using a longitudinal design. Longitudinal human studies
      are needed to describe the trajectory of nerve swelling for early identification
      of median nerve pathology. 

PMID- 24139198
TI  - Value of near-isovoxel ultrasound for evaluation of ductal communications with
      pancreatic cystic lesions: correlation with magnetic resonance
      cholangiopancreatography.
AB  - The aim of this study was to determine the value of near-isovoxel ultrasound
      (ISUS) using xMATRIX technology in assessment of ductal communications with
      pancreatic cystic lesions. Twenty patients with pancreatic cystic lesions (n =
      21) on magnetic resonance cholangiopancreatography (MRCP), underwent 2-D
      ultrasound (US) and subsequent ISUS using a matrix probe. Two observers assessed
      the presence of ductal communications with pancreatic cystic lesions for all
      MRCP, 2-D US, and ISUS images with multi-planar reformation, using a 5-point
      confidence scale. Weighted-kappa statistics and intra-class correlation
      coefficients were calculated. Inter-observer agreement for MRCP, 2-D US and ISUS
      was moderate, fair and moderate (0.475, 0.222 and 0.472), respectively. The intra
      class correlation coefficients between ISUS and MRCP was higher than that between
      2-D US and MRCP (0.8706 vs. 0.5353, observer 1; 0.7206 vs. 0.4818, observer 2,
      respectively). Correlation and inter-observer agreement were better with MRCP
      than with 2-D US. We conclude that ISUS may be useful in evaluating ductal
      communications with pancreatic cystic lesions.

PMID- 24139200
TI  - Safety of HPV vaccination: a FIGO statement.

PMID- 24139201
TI  - Address to participants at the General Assembly of the Pontifical Academy for
      Life.

PMID- 24139199
TI  - Illicit use of methadone and buprenorphine among adolescents and young adults in
      Sweden.
AB  - BACKGROUND: Illicit use of methadone and buprenorphine has been described as a
      growing problem in Sweden in recent years, and has been associated with an
      increased drug-related mortality. Critics claim that the substances have become
      popular among adolescents and that they function as a gateway to heroin use. The
      aim of this study is to investigate, firstly, the extent to which illicit use of
      methadone and buprenorphine occurs among adolescents and young adults in Sweden,
      and secondly, at what stage in a user's drug career these substances tend to
      appear. METHODS: The study is based on surveys and structured interviews on drug
      use among various populations of young people, in addition to qualitative
      interviews with 86 informants who, in their professional capacity, encounter
      adolescents or young adults who are using illicit drugs. RESULTS: Illicit use of
      methadone and buprenorphine is rare among young people in Sweden. According to
      high school surveys, less than 0.1% have tried these substances. Among young drug
      users in general, few have tried the substances, and there is nothing to indicate
      that they act as gateway drugs. Among adolescents and young adults with severe
      drug problems, however, the illicit use of methadone and buprenorphine is more
      common (54% in a compulsory care sample). These substances normally enter the
      drug career late, and few use them as their main drug of choice. Other
      prescription drugs, like benzodiazepines and tramadol, are used by adolescents to
      a far greater extent. Diversion and illicit use of methadone and buprenorphine is
      not seen as a serious problem by the professionals interviewed. A general view is
      that the substances are mainly used by people with a heroin or polydrug
      addiction, often for "self-medication" purposes. However, several informants
      express concern that methadone and buprenorphine may cause fatalities among young
      drug users without an opioid tolerance. CONCLUSIONS: Illicit use of methadone and
      buprenorphine among young drug users is not a widespread problem in Sweden. Harm
      reduction measures should target drug users with more severe problems, among whom
      illicit use of methadone and buprenorphine is more common and pose a medical
      risk. Illicit use of other prescription drugs, which are less controlled and more
      widely used by young people, is an important issue for further research.

PMID- 24139202
TI  - Chinese urban-rural disparity in pandemic (H1N1) 2009 vaccination coverage rate
      and associated determinants: a cross-sectional telephone survey.
AB  - OBJECTIVES: The present study aimed to examine the differences in pandemic (H1N1)
      2009 vaccination coverage rate between urban and rural areas in China, and to
      explore factors associated with any urban-rural differences. STUDY DESIGN: Cross
      sectional study. METHODS: Data were derived from a cross-sectional telephone
      survey performed in seven urban and two rural areas soon after the pandemic peak
      in China, concerning pandemic (H1N1) 2009 vaccination and associated knowledge,
      attitudes and practices among the general population in China. A total of 10 669
      participants aged 18 years and above participated in the study. RESULTS:
      Vaccination amongst rural residents was less than urban residents (8.9% vs 11.2%,
      P = 0.002). Among those who have not been immunized, 82.2% of rural respondents
      showed a willingness to get vaccinated against A/H1N1, significantly higher than
      that of urban respondents (55.3%). The major barrier to vaccination was reported
      as 'not being informed to get vaccination', of which there was a greater
      proportion in rural than urban population (71.9% vs 68.8%, P = 0.009). The
      analysis revealed a number of factors which contribute to this disparity:
      previous experience of vaccination against flu, degree of awareness of the free
      vaccination policy, and sociodemographic differences between urban and rural
      areas. CONCLUSIONS: Significant discrepancies existed in the pandemic (H1N1) 2009
      vaccination coverage rate and associated determinants, as well as the intention
      to get vaccinated between urban and rural residents. To improve the effectiveness
      of similar vaccination programmes in the future, campaigns for rural people need
      to be specifically tailored to address disparities in uptake.

PMID- 24139203
TI  - Client-provider interactions in provider-initiated and voluntary HIV counseling
      and testing services in Uganda.
AB  - BACKGROUND: Provider-initiated HIV testing and counselling (PITC) is based on
      information-giving while voluntary counselling and testing (VCT) includes
      individualised client-centered counseling. It is not known if the provider-client
      experiences, perceptions and client satisfaction with the information provided
      differs in the two approaches. METHODS: In 2008, we conducted structured
      interviews with 627 individuals in Uganda; 301 tested through PITC and 326
      through voluntary counselling and testing (VCT). We compared client experiences
      and perceptions based on the essential elements of consent, confidentiality,
      counseling, and referral for follow-up care. We conducted multivariate analysis
      for predictors of reporting information or counselling as sufficient. RESULTS: In
      VCT, 96.6% (282) said they were asked for consent compared to 91.3% (198) in PITC
      (P = 0.01). About the information provided, 92.0% (286) in VCT found it
      sufficient compared to 78.7% (221) in PITC (P = <0.01). In VCT 79.9% (246)
      thought their results were kept confidential compared to 71.7% (200) in PITC (P =
      0.02). Eighty percent (64) of HIV infected VCT clients said they were referred
      for follow-up care versus 87.3% (48) in PITC (p = 0.2). Predictors of perceived
      adequacy of information in PITC included an opportunity to ask questions (adj.RR
      1.76, CI 1.41, 2.18) and expecting the test results received (adj.RR 1.18, CI
      1.06, 1.33). For VCT significant factors included being given an opportunity to
      ask questions (adj.RR 1.62, CI 1.00, 2.60) and 3+ prior times tested, (adj.RR
      1.05, CI 1.00, 1.09). CONCLUSIONS: This study demonstrates good practices in the
      essential elements of HIV testing for both VCT and PITC. However, further quality
      enhancement is required in both testing approaches in relation to referral to HIV
      care post-test, client confidence in relation to confidentiality, and providing
      an opportunity to ask questions to address client-specific information needs.

PMID- 24139204
TI  - X ray screening at entry and systematic screening for the control of tuberculosis
      in a highly endemic prison.
AB  - BACKGROUND: Tuberculosis (TB) is a major issue in prisons of low and middle
      income countries where TB incidence rates are much higher in prison populations
      as compared with the general population. In the Rio de Janeiro (RJ) State prison
      system, the TB control program is limited to passive case-finding and supervised
      short duration treatment. The aim of this study was to measure the impact of X
      ray screening at entry associated with systematic screening on the prevalence and
      incidence of active TB. METHODS: We followed up for 2 years a RJ State prison for
      adult males (1429 inmates at the beginning of the study) and performed, in
      addition to passive case-finding, 1) two "cross-sectional" X-ray systematic
      screenings: the first at the beginning of the study period and the second 13
      months later; 2) X-ray screening of inmates entering the prison during the 2 year
      study period. Bacteriological examinations were performed in inmates presenting
      any pulmonary, pleural or mediastinal X-ray abnormality or spontaneously
      attending the prison clinic for symptoms suggestive of TB. RESULTS: Overall, 4326
      X-rays were performed and 246 TB cases were identified. Prevalence among entering
      inmates remained similar during 1st and the 2nd year of the study: 2.8% (21/754)
      and 2.9% (28/954) respectively, whereas prevalence decreased from 6.0% (83/1374)
      to 2.8% (35/1244) between 1st and 2nd systematic screenings (p < 0.0001).
      Incidence rates of cases identified by passive case-finding decreased from 42 to
      19 per 1000 person-years between the 1st and the 2nd year (p < 0.0001). Cases
      identified by screenings were less likely to be bacteriologically confirmed as
      compared with cases identified by passive-case finding. CONCLUSIONS: The strategy
      investigated, which seems highly effective, should be considered in highly
      endemic confined settings such as prisons.

PMID- 24139205
TI  - Application of the Antipsychotic Use in Dementia Assessment audit tool to
      facilitate appropriate antipsychotic use in long term care residents with
      dementia.
AB  - Approximately 25% of all nursing home residents take antipsychotics for
      behavioral disturbances, despite limited efficacy and warnings against their use.
      The purpose of this quality improvement project was to test the utility of an
      educational in-service to facilitate the appropriate use of antipsychotics for
      nursing home residents with dementia. A single group pre/post design targeting
      the reduction of antipsychotic medications in older adults was guided by Rogers'
      Diffusion of Innovations theory. Descriptive analyses were done to evaluate
      antipsychotic use and supporting documentation at baseline and 2 months following
      an educational intervention that focused on appropriate antipsychotic use,
      documentation requirements and non-pharmacologic interventions. The prescribing
      rate for antipsychotics showed a reduction from 20.3% to 15.4% and nursing
      documentation of non-pharmacological interventions increased from 16.7% to 75%.
      Assuring appropriate use of antipsychotics is currently mandated and is
      consistent with high quality, person centered care. This simple, yet
      individualized educational intervention and assessment can serve as a model for
      use in other long term care facilities. 

PMID- 24139206
TI  - The association between participation in social activity and depressive symptoms
      in institutionalized elders in Taiwan.
AB  - Depression can be a significant predictor of rapid health decline in
      institutionalized elders. Non-pharmacologic interventions for depression may
      include meaningful and enjoyable social activities. This cross-sectional,
      descriptive correlational study was to examine the associations between three
      components (frequency, meaningfulness and enjoyment) of nine types of social
      activities and depressive symptoms in a sample of Taiwanese elders living in long
      term care facilities. Results indicated that meaningful and enjoyable activities
      were associated with fewer depressive symptoms among institutionalized elders.
      Clinically depressed elders (GDS score >= 6) were significantly less likely to
      report a sense of meaning in 6 of 9 social activities, or to report as enjoyable
      7 of 9 social activities investigated. Findings suggest that elders' contemplate
      assignation of meaning of their subjective experiences with social activities,
      and it would behoove clinical nurses to pay attention to the essential purpose
      and perceived benefit of the designed social activities. 

PMID- 24139207
TI  - The impact of complex chronic diseases on care utilization among assisted living
      residents.
AB  - PURPOSE: Many residents of assisted living (AL) have chronic diseases that are
      difficult to manage, including congestive heart failure (CHF), chronic
      obstructive pulmonary disease (COPD) and diabetes mellitus (DM). We estimated the
      amount and intensity of care delivered by the staff for residents with these
      conditions. METHODS: We performed a secondary data analysis from the Maryland
      Assisted Living (MDAL) Study (399 residents, 29 facilities). In-person
      assessments included measures of cognition, function, depression, and general
      medical health. Diagnosis of CHF, COPD, and DM, as well as current medications
      was abstracted from AL medical charts. Measures of care utilization were
      operationalized at the resident level as: 1) minutes per day of direct care
      (caregiver activity scale [CAS]), 2) subjective staff ratings of care burden, and
      3) assigned AL "level of care" (based on state regulatory criteria). RESULTS: In
      best fit regression models, CHF and DM were not significant predictors of the
      evaluated care utilization measures; however, COPD was independently associated
      with increased minutes per day of direct care - 34% of the variance in the
      caregiver activity scale was explained by degree of functional dependency,
      cognitive impairment, age, and presence of COPD. Functional dependency,
      depressive symptoms, and age explained almost a quarter (23%) of the variance of
      staff care burden rating. For the AL level of care intensity rating, degree of
      functional dependency, level of cognition, and age were significant correlates,
      together explaining about 28% of the variance. CONCLUSION: The presence of COPD
      was a significant predictor of time per day of direct care. However, CHF and DM
      were not correlates of care utilization measures. Functional and cognitive
      impairment was associated with measures of care utilization, reiterating the
      importance of these characteristics in the utilization and intensity of care
      consumed by AL residents. Further study of this population could reveal other
      forms and amounts of care utilization.

PMID- 24139208
TI  - Adenomatous polyposis coli gene involvement in ileal enterochromaffin cell
      neuroendocrine neoplasms.
AB  - The adenomatous polyposis coli gene is a key tumor suppressor gene. Alterations
      in this gene have been found in most sporadic colon cancers; associated with
      familial adenomatous polyposis; and found in neoplasms of other organs, such as
      the liver, stomach, lung, breast, and cerebellar medulloblastoma. In the
      heterogeneous group of neuroendocrine neoplasms of the gastrointestinal tract,
      the involvement of adenomatous polyposis coli is debated, and only occasional
      reports found adenomatous polyposis coli alterations in foregut and midgut
      neuroendocrine neoplasms, with adenomatous polyposis coli mutations only in the
      latter. To elucidate the penetrance of adenomatous polyposis coli alterations in
      ileal neuroendocrine neoplasms, we performed DNA fragment analysis (loss of
      heterozygosity for 5q22-23 and 5q23) and sequencing on the mutation cluster
      region of the adenomatous polyposis coli gene on 30 ileal enterochromaffin cell
      neuroendocrine neoplasms. Adenomatous polyposis coli gene mutations were detected
      in 23% of cases (7/30); in particular, 57% were missense and 14%,
      nonsense/frameshift, all novel and different from those reported in colorectal or
      other cancers. Loss of heterozygosity analysis demonstrated a deletion frequency
      of 15% (4/27). No association was found with features of tumor progression. Our
      observations support the involvement of somatic adenomatous polyposis coli
      alterations in tumorigenesis of ileal enterochromaffin cell neuroendocrine
      neoplasms; the mechanisms of adenomatous polyposis coli gene inactivation appear
      to be different from those reported in other tumor types. 

PMID- 24139209
TI  - Characteristic tumor growth patterns as novel histomorphologic predictors for
      lymph node metastasis in papillary thyroid carcinoma.
AB  - The aim of this study was to investigate the efficaciousness of histological
      tumor growth patterns in the prediction of lymph node metastasis (LNM) in
      papillary thyroid carcinoma (PTC). All combinations of infiltrative tumor border,
      lateral tubular growth, and intraglandular dissemination were assessed for their
      ability to predict LNM in 229 patients. In addition, we analyzed their predictive
      value within subgroups based on the tumor size and number of tumor nodules. Each
      tumor growth pattern was significantly associated with LNM, as 11 of the 12
      combinations of these 3 patterns were found to be independently predictive of LNM
      (P < .05). Similar results were observed in both univariate and multivariate
      logistic regression analyses of PTCs, grouped according to the tumor size and
      number of tumor nodules. This study has shown that histological features
      suggestive of invasive tumor growth, including infiltrative tumor border and
      lateral tubular growth, may be used as independent predictive factors of LNM in
      PTC, and can improve treatment and follow-up strategies for PTC. 

PMID- 24139210
TI  - Lymph node metastasis in early gastric cancer: evaluation of a novel method for
      measuring submucosal invasion and development of a nodal predicting index.
AB  - After endoscopic resection of early gastric cancer (EGC), it is imperative to
      accurately determine whether follow-up surgery is indicated, since this technique
      is used as a first line of treatment. Herein, we developed a scoring system to
      indicate the risk of lymph node metastasis in submucosal EGC (smEGC), and present
      a novel method to measure depth of submucosal invasion. In our series, 15.9% of
      the smEGC presented with lymph node metastasis. A nodal prediction index, based
      on the variables extracted from the univariate analysis and defined as nodal
      prediction index = (2.128 * lymphovascular tumor emboli) + (1.083 * submucosal
      invasion width >= 0.75 cm) + (0.507 * submucosal invasion depth >= 1000 MUm) +
      (0.515 * infiltrative growth pattern), yielded an area under the receiver
      operating characteristic curve of 0.809 (P =.000, 95% CI = 0.713-0.096) in a
      training group, and showed comparable result in validation group (0.886, P =.000,
      95% CI = 0.796-0.977). Depth of invasion was statistically higher in the
      metastatic group when measured from the lowest point of an imaginary line in
      continuity with the adjacent muscularis mucosa to the point of deepest tumor
      penetration, but not when using the classic measurement method. The area under
      the receiver operating characteristic curve of the alternative measurement method
      was 0.652 (P =.013, 95% CI = 0.550-0.754) compared to 0.620 for the classic
      measurement method (P =.0480, 95% CI = 0.509-0.731). In deciding whether surgery
      is indicated after endoscopic submucosal dissection for smEGCs, we recommend to
      test our alternative method of measuring submucosal invasion and to evaluate our
      nodal prediction index as an adjunct tool.

PMID- 24139211
TI  - Clinicopathologic features and prognosis of duodenal adenocarcinoma and
      comparison with ampullary and pancreatic ductal adenocarcinoma.
AB  - Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic
      features and prognostication data for DAC are limited. There are no published
      studies directly comparing the prognosis of DAC to that of ampullary
      adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after
      resection. In this study, we examined the clinicopathologic features of 68
      patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent
      resection. Patient clinicopathologic and survival information were extracted from
      medical records. Statistical analysis was performed using Statistical Package for
      the Social Sciences with 2-sided significance level of .05. Patients with DAC had
      higher American Joint Committee on Cancer (AJCC) stage than AA patients (P =
      .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with
      overall survival in DAC patients. Patients with DAC or AA had lower frequencies
      of lymph node metastasis and positive margin and better survival than those with
      PDA (P < .05). However, no differences in nodal metastasis, margin status, or
      survival were observed between DAC patients and those with AA. Our study showed
      that lymph node metastasis and AJCC stage are important prognostic factors for
      overall survival in DAC patients. Patients with DAC had less frequent nodal
      metastasis and better prognosis than those with PDA. There was no significant
      difference in prognosis between DAC and AA. 

PMID- 24139212
TI  - qPCR increases sensitivity to detect cytomegalovirus in formalin-fixed, paraffin
      embedded tissue of gastrointestinal biopsies.
AB  - Histopathologic diagnosis of gastrointestinal (GI) tract cytomegaloviral (CMV)
      infection relies on hematoxylin and eosin (H&E)-stained tissue, along with the
      aid of immunohistochemistry (IHC). However, non-classic appearing inclusions or
      atypical IHC staining patterns remain an ongoing concern for pathologists. We
      reported the use of real-time polymerase chain reaction (qPCR) on nucleic acid
      extracted from paraffin-embedded, formalin-fixed tissue of GI biopsies from cases
      of CMV infection (n = 91) diagnosed by H&E and IHC. Seventy-nine biopsies,
      including normal colon biopsies (n = 35), active colitis (n = 25), and active
      duodenitis (n = 19), were used as negative controls. Of 91 CMV-positive biopsies
      diagnosed by histology, 88 tested positive by qPCR, with a sensitivity of 96.7%.
      Of 79 negative controls, 78 were negative and 1 positive by qPCR, resulting in a
      specificity of 98.7%. Of the cases that were positive for CMV by histopathology,
      there were an additional 40 biopsies taken from these patients either during the
      same or previous procedures, some taken just days prior, which were negative for
      CMV by histology. Interestingly, 22 (55%) of these biopsies tested positive by
      qPCR, which correlated well with additional clinical CMV results. By defining
      qPCR as the "gold standard" for a CMV result, histology (H&E and/or IHC) had a
      sensitivity and specificity of 79% and 97%, respectively. Eighteen biopsies were
      found negative by H&E and equivocal by IHC. Among them, 14 (78%) tested positive
      for CMV by qPCR, which also correlated well with additional clinical results.
      qPCR is a sensitive, specific, and rapid molecular tool that may be helpful to
      aid in early diagnosis of CMV infection on equivocal or clinically highly
      suspicious small GI biopsies. 

PMID- 24139213
TI  - Development of a multivariate model to predict the likelihood of carcinoma in
      patients with indeterminate peripheral lung nodules after a nondiagnostic
      bronchoscopic evaluation.
AB  - Studies have shown that fluorescence in situ hybridization (FISH) testing
      increases lung cancer detection on cytology specimens in peripheral nodules. The
      goal of this study was to determine whether a predictive model using clinical
      features and routine cytology with FISH results could predict lung malignancy
      after a nondiagnostic bronchoscopic evaluation. Patients with an indeterminate
      peripheral lung nodule that had a nondiagnostic bronchoscopic evaluation were
      included in this study (N = 220). FISH was performed on residual bronchial
      brushing cytology specimens diagnosed as negative (n = 195), atypical (n = 16),
      or suspicious (n = 9). FISH results included hypertetrasomy (n = 30) and negative
      (n = 190). Primary study end points included lung cancer status along with time
      to diagnosis of lung cancer or date of last clinical follow-up. Hazard ratios
      (HRs) were calculated using Cox proportional hazards regression model analyses,
      and P values < .05 were considered statistically significant. The mean age of the
      220 patients was 66.7 years (range, 35-91), and most (58%) were men. Most
      patients (79%) were current or former smokers with a mean pack year history of
      43.2 years (median, 40; range, 1-200). After multivariate analysis,
      hypertetrasomy FISH (HR = 2.96, P < .001), pack years (HR = 1.03 per pack year up
      to 50, P = .001), age (HR = 1.04 per year, P = .02), atypical or suspicious
      cytology (HR = 2.02, P = .04), and nodule spiculation (HR = 2.36, P = .003) were
      independent predictors of malignancy over time and were used to create a
      prediction model (C-statistic = 0.78). These results suggest that this
      multivariate model including test results and clinical features may be useful
      following a nondiagnostic bronchoscopic examination. 

PMID- 24139214
TI  - P-cadherin and vimentin are useful basal markers in breast cancers.
AB  - Basal-like breast cancer (BLBC) is the breast cancer subtype defined by gene
      profiling and generates keen clinical interest. Immunohistochemical panels using
      basal cytokeratins and epidermal growth factor receptor are widely adopted for
      its identification. Nonetheless, there are concerns about the risk for missing
      some true BLBCs. Both P-cadherin and vimentin have been proposed as BLBC markers,
      but their usefulness for BLBC classification has not been well documented. In
      this study, we evaluated by immunohistochemistry their expression in a large
      cohort of breast carcinoma. Cancers expressing vimentin or P-cadherin showed BLBC
      related morphological features (high grade, presence of necrosis, and lymphocytic
      infiltration; P < .001 for all except P = .006 for vimentin with lymphocytic
      infiltration) and immunohistochemical profile (P < .001 for all markers tested
      except P = .007 for vimentin with human epidermal growth factor receptor 2).
      Concordantly, they were significantly associated with BLBC (P < .001 for both).
      Nonetheless, they did not appear to be good stand-alone BLBC markers. Compared
      with the commonly used reference panel, the specificity (95.9%) and sensitivity
      (43.1%) of coexpression of vimentin and P-cadherin were better than most single
      markers or their combinations tested. Moreover, their coexpression was
      significantly associated with basal features in non-BLBCs and worse disease-free
      survival in triple-negative breast cancers (hazard ratio, 2.232; P = .027). This
      raised the possibility that the vimentin and P-cadherin combination can be used
      to identify BLBC especially those that were missed by the commonly used basal
      cytokeratins and epidermal growth factor receptor panel. Together, P-cadherin and
      vimentin could be adjunctive to the commonly used immunohistochemical surrogates
      for BLBC identification. 

PMID- 24139215
TI  - The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and
      their correlation with clinical outcome.
AB  - The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The
      prognosis of intrahepatic cholangiocarcinoma is poor, and a better understanding
      of intrahepatic cholangiocarcinoma tumor biology is needed to more accurately
      predict clinical outcome and to suggest potential targets for more effective
      therapies. v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF
      are frequently mutated oncogenes that promote carcinogenesis in a variety of
      tumor types. In this study, we analyze a large set of intrahepatic
      cholangiocarcinoma tumors (n = 54) for mutations in these genes and compare the
      clinical outcomes of wild type versus KRAS and BRAF mutant cases. Of 54 cases,
      7.4% were mutant for KRAS, 7.4% were mutant for BRAF, and these were mutually
      exclusive. These mutant cases were associated with a higher tumor stage at time
      of resection and a greater likelihood of lymph node involvement. These cases were
      also associated with a worse long-term overall survival. Therefore, testing for
      KRAS and BRAF mutations could be a valuable adjunct in improving both prognosis
      and outcome stratification among patients with intrahepatic cholangiocarcinoma. 

PMID- 24139216
TI  - Immunoglobulin G4-related multiple systemic aneurysms and splenic aneurysm
      rupture during steroid therapy.
AB  - Immunoglobulin G4 (IgG4)-related disorders in various organs have recently been
      described, but multiple systemic aneurysms have not yet been reported. Here, we
      present a 68-year-old Japanese man with multiple systemic aneurysms and tumor
      forming pericoronary arteritis who was undergoing low-dose corticosteroid
      therapy. Elevated serum IgG4 (2390 mg/dL) and IgG4-positive plasmacyte
      infiltration in the salivary glands led to a diagnosis of IgG4-related disease.
      High-dose corticosteroid therapy was initiated, whereupon the inflammatory
      lesions shrank. However, the large, well-developed common hepatic aneurysm and
      splenic aneurysm did not change. Our patient died of splenic aneurysm rupture in
      the sixth month of treatment. The autopsy revealed IgG4-positive plasmacyte
      infiltration in the coronary wall and a thinned splenic aneurysm wall. This case
      suggests that early high-dose corticosteroid therapy may be necessary for the
      treatment of IgG4-related cardiovascular disorders. A minor salivary gland biopsy
      might facilitate the early diagnosis of IgG4-related disease even if (18)F
      fluorodeoxyglucose positron emission tomography provides no inflammatory
      findings. 

PMID- 24139217
TI  - Chronic pain and pain-related disability across psychiatric disorders in a
      clinical adolescent sample.
AB  - BACKGROUND: People who suffer from psychiatric disorders are burdened with a high
      prevalence of chronic illnesses and pain, but evidence on pain prevalence among
      adolescents with psychiatric disorders is scarce. The aim of this study was to
      investigate the frequency and location of self-reported chronic pain and pain
      related disability in adolescent psychiatric patients. METHODS: This study was
      part of the larger Health Survey administered at the Department of Child and
      Adolescent Psychiatry (CAP) at St. Olav's University Hospital, in Trondheim,
      Norway. All patients aged 13-18 years who visited the CAP clinic at least once
      between February 15, 2009 and February 15, 2011 were invited to participate. A
      total of 717 (43.5% of eligible/invited patients) participated; of these, 566
      were diagnosed with one or more psychiatric disorders. The adolescents completed
      a questionnaire, which included questions about pain and pain-related disability.
      Clinical diagnoses were classified by a clinician according to International
      Statistical Classification of Diseases and Related Health Problems, 10th revision
      criteria. RESULTS: In adolescents with psychiatric disorders, 70.4% reported
      chronic pain, and 37.3% experienced chronic pain in three or more locations
      (multisite pain). Chronic musculoskeletal pain was the most prevalent type of
      pain (57.7%). Pain-related disability was found in 22.2% of the sample. The
      frequency of chronic pain and multisite pain increased with age, and girls
      reported a higher frequency of chronic pain, multisite pain and pain-related
      disability than boys did. There was an increased risk of chronic pain among
      adolescents with mood or anxiety disorders versus those with hyperkinetic
      disorders, yet this was not present after adjusting for sex. Comorbidity between
      hyperkinetic and mood or anxiety disorders involved an increased risk of pain
      related disability. CONCLUSIONS: In this study, seven out of 10 adolescents with
      psychiatric disorders reported chronic pain. These findings indicate the
      importance of early detection of chronic pain in adolescents with psychiatric
      disorders, to provide targeted treatment and reduce poor long-term outcomes.

PMID- 24139218
TI  - External validation of a substratification of the American Association for the
      Surgery of Trauma renal injury scale for grade 4 injuries.
AB  - BACKGROUND: The traditional American Association for the Surgery of Trauma (AAST)
      grading of renal injury does not adequately identify the subset of patients who
      are most likely to require intervention for bleeding. Recently, several high-risk
      criteria (HRC) for bleeding after renal injury were identified, and we sought to
      externally validate these criteria among patients with grade 4 renal injury.
      STUDY DESIGN: All patients presenting to a level I trauma center with blunt grade
      4 renal injuries from 2003 to 2010 were reviewed, and stage was determined by the
      1989 AAST staging criteria. Dependent variables included the presence of a hilar
      injury or any of the HRC (perirenal hematoma size, intravascular contrast
      extravasation, and medial or complex laceration). The primary outcome was the
      need for intervention (renorrhaphy, nephrectomy, or angiography) for hemodynamic
      instability. RESULTS: A total of 84 patients with grade 4 renal lacerations were
      identified. Two or more HRC were present in 18 patients (21%), and intervention
      for hemodynamic instability was performed in 14 patients (17%). Compared with
      patients with 0 or 1 HRC, those with >= 2 HRC were approximately 25 times more
      likely to require intervention for hemodynamic instability (odds ratio [OR]24.9,
      95% CI 5.5 to 112.9, p < 0.001). Patients with no HRC were unlikely to require
      intervention for hemodynamic instability. CONCLUSIONS: Among patients with blunt
      grade 4 renal injury, the presence of >= 2 HRC effectively predicts the need for
      intervention for hemodynamic instability and can be used to identify patients who
      require intensive monitoring. The AAST grading system for renal injury should be
      modified to better reflect injury severity.

PMID- 24139219
TI  - Invited commentary.

PMID- 24139220
TI  - The Hartford Consensus: THREAT, a medical disaster preparedness concept.

PMID- 24139221
TI  - Should initial mastectomy rates increase?

PMID- 24139222
TI  - Reply: To PMID 23490543.

PMID- 24139224
TI  - Evidence-based classification of low back pain in the general population: one
      year data collected with SMS Track.
AB  - BACKGROUND: It was previously assumed that low back pain (LBP) is a disorder that
      can be classified as acute, subacute and chronic. Lately, the opinion seems to
      have veered towards a concept of it being a more recurrent or cyclic condition.
      Interestingly, a recent review of the literature indicated that LBP in the
      general population is a rather stable condition, characterized as either being
      present or absent. However, only one of the reviewed studies had used frequent
      data collection, which would be necessary when studying detailed course patterns
      over time. It was the purpose of this study to see, if it was possible to
      identify whether LBP, when present, is rather episodic or chronic/persistent.
      Further, we wanted to see if it was possible to describe any specific course
      profiles of LBP in the general population. METHODS: In all, 293 49/50-yr old
      Danes, who previously participated in a population-based study on LBP were
      invited to respond to 26 fortnightly text-messages over one year, each time
      asking them the number of days they had been bothered by LBP in the past two
      weeks. The course patterns for these individuals were identified through manual
      analysis, by observing the interplay between non-episodes and episodes of LBP. A
      non-episode of LBP was defined as a period of at least one month without LBP as
      proposed by de Vet et al. A fortnight with at least one day of pain was defined
      as a pain fortnight (FN). At least one pain FN surrounded by a non-episode on
      each side was defined as an episode of LBP. After some preliminary observations
      of the spread of data, episodes were further classified as brief (consisting of
      only one pain FN) or longer (if there were at least 2 pain FNs in a row). An
      episode of at least 6 pain FNs in a row (i.e. 3 months) was defined as a long
      lasting episode. RESULTS: In all, 261 study subjects were included in the
      analyses, for which 7 distinct LBP subsets could be identified. These could be
      grouped into three major clusters; those mainly without LBP (35%), those with
      episodic LBP (30%) and those with persistent LBP (35%). There was a positive
      association between number of episodes and their duration. CONCLUSION: In this
      study population, consisting of 50-yr old persons from the general population,
      LBP, when present, could be classified as either 'episodic' or 'mainly
      persistent'. About one third was mainly LBP-free throughout the year of study.
      More information is needed in relation to their relative proportions in various
      populations and the clinical relevance of these subgroups.

PMID- 24139225
TI  - Three-dimensional conformal radiotherapy with concurrent chemotherapy for
      postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy
      and failure pattern.
AB  - BACKGROUND: To assess the therapeutic outcome and failure pattern of three
      dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy
      (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical
      surgery. METHODS: Treatment outcome and failure pattern were retrospectively
      evaluated in 83 patients with localized cervical and thoracic recurrences after
      radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT
      based CCRT (median radiation dose 60 Gy), in which 39 received concurrent
      cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus
      cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT.
      RESULTS: With a median follow-up of 34 months (range, 2-116 months), the 3-year
      overall survival (OS) of all the patients was 51.8% and the median OS time was
      43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete
      remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response
      after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy
      (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed
      that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p =
      0.010) were independent predictors of OS. Forty-seven patients had progressive
      diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant
      metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%).
      CONCLUSIONS: 3DCRT-based CCRT is effective in postoperatively recurrent
      esophageal SCC. Patients that obtained complete remission after CCRT appeared to
      achieve long-term OS and might benefit from concurrent TP regimen. Local and
      distant failures remained high and prospective studies are needed to validate
      these factors.

PMID- 24139226
TI  - A novel autoantibody against ephrin type B receptor 2 in acute necrotizing
      encephalopathy.
AB  - Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain
      necrosis, suggested to be due to breakdown of the blood-brain barrier (BBB). We
      experienced a rare case of ANE complicated with systemic lupus erythematosus
      (SLE), and found that the patient's serum (V10-5) had binding activity to human
      umbilical vein endothelial cells (HUVECs). By SARF (Serological identification
      system for Autoantigens using a Retroviral vector and Flow cytometry) method
      using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was
      integrated with cDNA identical to EphB2, which plays critical roles in neuronal
      cells and endothelial cells. HUVECs and human brain microvascular endothelial
      cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected
      cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In
      this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody
      may define a novel group of brain disorders. Anti-EphB2 antibody can interfere
      not only with endothelial cells including those of the BBB (acting as an anti
      endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal
      antibody) if the BBB has been breached. Future studies should determine the
      clinical prevalence and specificity of anti-EphB2 antibody, and the molecular
      mechanisms by which anti-EphB2 antibody mediates neuronal and vascular
      pathological lesions. 

PMID- 24139227
TI  - African ethnicity can influence immunological responses to highly active
      antiretroviral therapy and immunological success at 48 months: a retrospective
      pilot study.
AB  - OBJECTIVE: To assess whether African ethnicity is independently associated with a
      poorer CD4 reconstitution with highly active antiretroviral therapy (HAART)
      compared to Caucasian ethnicity. METHODS: We conducted a retrospective
      epidemiological study among 575 HIV-1-positive patients at our center and defined
      immunological success as the presence of blood CD4 lymphocyte counts>500
      cells/mm3 in more than 50% of the values collected from 6 to 48 months after
      beginning HAART. Patients displaying an HIV-1 viral load>200 copies/ml or more
      than one HIV-1 viral load between 20 and 200 copies/ml during follow-up, were
      excluded. Patients with baseline blood CD4 counts>500 cells/mm3 were also
      excluded. RESULTS: Two hundred and eighty patients met the inclusion criteria and
      no exclusion criteria. After 48 months of HAART, blood CD4 lymphocyte counts were
      lower in Africans than in Caucasians: 449 (65-975) vs. 569 (131-1698) cells/mm3
      (p=0.02). Immunological success was present in 142/220 (64.5%) Caucasians vs.
      29/60 (48.3%) Africans (p=0.02). African ethnicity was independently associated
      with the absence of immunological success (odds ratio 2.22, 95% confidence
      interval 1.097-4.504; p=0.02) despite similar baseline blood CD4 counts (219 vs.
      204 cells/mm3, p=0.72). CONCLUSION: Our findings suggest that African ethnicity
      is independently associated with a poorer CD4 reconstitution during HAART than
      Caucasian ethnicity.

PMID- 24139228
TI  - Subnormal and waning immunity to tetanus toxoid in previously vaccinated HIV
      infected children and response to booster doses of the vaccine.
AB  - Little is known regarding waning immunity to tetanus toxoid (TT) in HIV-infected
      children and the need for booster doses before the recommended interval of 5-10
      years. Anti-tetanus antibodies were assessed by ELISA in 24 HIV-infected and 24
      control children. A protective level (>0.1 IU/ml) of TT antibodies was observed
      in 62% of HIV-infected children and in 100% of controls. HIV-infected children
      with five doses had a significantly (p=0.01) lower prevalence of protective
      immunity compared to controls. Follow-up anti-TT antibody levels in nine HIV
      infected children declined from 1.27 to 0.26 IU/ml, but levels did not decline in
      the seven controls; five of the seven (71%) children with a non-protective level
      of antibodies responded with a level>0.16 IU/ml following one booster dose of the
      vaccine. HIV-infected children may need TT boosters before the recommended 5-10
      years.

PMID- 24139229
TI  - Secretion of polyhydroxybutyrate in Escherichia coli using a synthetic biological
      engineering approach.
AB  - BACKGROUND: Polyhydroxyalkanoates (PHAs) are a group of biodegradable plastics
      that are produced by a wide variety of microorganisms, mainly as a storage
      intermediate for energy and carbon. Polyhydroxybutyrate (PHB) is a short-chain
      length PHA with interesting chemical and physical properties. Large scale
      production of PHB is not wide-spread mainly due to the downstream processing of
      bacterial cultures to extract the PHB. Secretion of PHB from Escherichia coli
      could reduce downstream processing costs. PHB are non-proteinaceous polymers,
      hence cannot be directly targeted for secretion. Phasin, PhaP1, is a low
      molecular weight protein that binds to PHB, reducing PHB granule size. In this
      study PHB is indirectly secreted with PhaP1 from E. coli via type I secretion
      using HlyA signal peptides. RESULTS: This study demonstrated the successful
      secretion of phasin and phasin bound PHB outside of the cell and into the culture
      medium. The secretion of PHB was initiated between 24 and 48 h after induction.
      After 48 h of culturing, 36% of the total PHB produced in the secreting strain
      was collected in the secreted fraction and 64% remained in the internal fraction.
      To further support the findings of this study, the PHB secretion phenomenon was
      observed using SEM. CONCLUSIONS: From this study, the ability to use type I
      secretion to: 1) secrete phasin and 2) successfully secrete PHB has been shown.

PMID- 24139230
TI  - Long noncoding RNAs in development: solidifying the Lncs to Hox gene regulation.
AB  - Long noncoding RNAs (lncRNAs) are pervasively expressed in mammals, although
      their functions during development remain poorly understood. In this issue of
      Cell Reports, Delpretti et al. and Li et al. suggest essential roles for lncRNAs
      in coordinating Hox gene expression. 

PMID- 24139231
TI  - Is posterior percutaneous screw-rod instrumentation a safe and effective
      alternative approach to TLSO rigid bracing for single-level pyogenic
      spondylodiscitis? Results of a retrospective cohort analysis.
AB  - BACKGROUND CONTEXT: Currently, treatment for patients diagnosed with
      noncomplicated (ie, known infectious agent, no neurologic compromise, and
      preserved spinal stability) pyogenic spondylodiscitis (PS) is based on
      intravenous antibiotics and rigid brace immobilization. Since January 2010, we
      started offering our patients percutaneous posterior screw-rod instrumentation as
      an alternative approach to rigid bracing. Supposed benefits of posterior
      percutaneous instrumentation over rigid bracing are earlier free mobilization,
      increased comfort, and faster recovery. PURPOSE: To evaluate safety and
      effectiveness of posterior percutaneous spinal instrumentation for single-level
      PS and compare clinical and quality-of-life outcomes with standard
      thoracolumbosacral orthosis (TLSO) rigid bracing. STUDY DESIGN/SETTING:
      Retrospective observational cohort study. PATIENT SAMPLE: Twenty-seven patients
      consecutively diagnosed with single-level noncomplicated lower thoracic or lumbar
      PS from January 2010 to December 2011. OUTCOME MEASURES: Healing rate, healing
      time, and changes in segmental kyphosis Cobb angle were compared in the two
      treatment groups. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      and complete blood count at regular time points until complete healing were also
      obtained. Self-report measures included Visual Analog Scale (VAS), Short-Form 12
      (SF-12), and EuroQol five-dimension (EQ-5D) questionnaires. METHODS: At
      enrollment, patients were offered to choose between 24/7 TLSO rigid bracing for 3
      to 4 months and bridging posterior percutaneous screw-rod instrumentation
      followed by soft bracing for 4 weeks after surgery. All patients underwent
      antibiotic therapy accordingly to isolated infectious agents. Patients were seen
      in the clinic at 1, 3, 6, and 9 months, and ESR, CRP, complete blood count, VAS,
      SF-12, and EQ-5D questionnaires were obtained. Segmental kyphosis was measured at
      diagnosis and at 9 months follow-up. Two-way repeated-measures analysis of
      variance was used to assess group and time differences across time points.
      RESULTS: Fifteen patients chose conservative treatment, whereas 12 patients chose
      surgical treatment. Complete infection healing was achieved in all patients with
      no significant differences in healing time (p<.366). C-reactive protein and ESR
      levels decreased in both groups accordingly with positive response to therapy
      with no significant differences. Surgically treated patients had significantly
      lower VAS scores at 1 month (2.76+/-0.80 vs. 5.20+/-1.21, p<.001) and 3 months
      (2.31+/-0.54 vs. 2.85+/-0.54, p<.016) post-diagnosis over TLSO patients.
      Moreover, surgery patients also showed steeper and statistically significant
      improvements in SF-12 scores over TLSO patients at 1, 3, and 6 months post
      diagnosis (p<.012); no significant differences were detected at the other time
      points. EuroQol five-dimension index was significantly higher in surgery patients
      at 1 month (0.764+/-0.043 vs. 0.458+/-0.197, p<.001) and 3 months (0.890+/-0.116
      vs. 0.688+/-0.142, p<.001); no significant changes were observed in segmental pre
      and posttreatment kyphosis between the two groups. No instrumentation-related
      complications were observed in any patient. CONCLUSIONS: Posterior percutaneous
      spinal instrumentation is a safe, feasible, and effective procedure in relieving
      pain, preventing deformity, and neurologic compromise in patients affected by
      noncomplicated lower thoracic (T9-T12) or lumbar PS. Posterior instrumentation
      did not offer any advantage in healing time over TLSO rigid bracing because
      infection clearance is strongly dependent on proper antibiotic therapy.
      Nevertheless, surgical stabilization was associated with faster recovery, lower
      pain scores, and improved quality of life compared with TLSO conservative
      treatment at 1, 3, and 6 months after treatment.

PMID- 24139232
TI  - Comparison of helicopter versus ground transport for the interfacility transport
      of isolated spinal injury.
AB  - BACKGROUND CONTEXT: The use and need of helicopter aeromedical transport systems
      (HEMSs) in health care today is based on the basic belief that early definitive
      care improves outcomes. Helicopter aeromedical transport system is perceived to
      be safer than ground transport (GT) for the interfacility transfer of patients
      who have sustained spinal injury because of the concern for deterioration of
      neurologic function if there is a delay in reaching a higher level of care.
      However, the use of HEMS is facing increasing public scrutiny because of its
      significantly greater cost and unique risk profile. PURPOSE: The aim of the study
      was to determine whether GT for interfacility transfer of patients with spinal
      injury resulted in less favorable clinical outcomes compared with HEMS. STUDY
      DESIGN/SETTING: Retrospective review of all patients transferred to a Level 1
      trauma center. PATIENT SAMPLE: Patients identified from the State Trauma Registry
      who were initially seen at another hospital with an isolated diagnosis of injury
      to the spine and then transferred to a Level 1 trauma center over a 2-year
      period. OUTCOME MEASURES: Neurologic deterioration, disposition from the
      emergency department, in-hospital mortality, interfacility transfer time,
      hospital length of stay, nonroutine discharge, and radiographic evidence of
      worsening spinal injury. METHODS: Patients with International Classification of
      Diseases, Ninth Revision (ICD-9) codes for injury to the spine were selected and
      records were reviewed for demographics and injury details. All available spine
      radiographs were reviewed by an orthopedic surgeon blinded to clinical data and
      transport type. Chi-square and t tests and multivariate linear and logistic
      regression models were done using STATA version 10. RESULTS: A total of 274 spine
      injury patients were included in our analysis, 84 (31%) of whom were transported
      by HEMS and 190 (69%) by GT. None of the GT patients had any deterioration in
      neurologic examination nor any detectable alteration in the radiographic
      appearance of their spine injury attributable to the transportation process.
      Helicopter aeromedical transport system resulted in significantly less transfer
      time with an average time of 80 minutes compared with 112 minutes with GT
      (p<.001). Ultimate disposition included 175 (64%) patients discharged to home, 15
      (5%) expired patients, and 84 (31%) discharged to extended care facilities. After
      adjusting for patient age and Injury Severity Score, the use of GT was not a
      significant predictor of in-hospital mortality (odds ratio, 1.4; 95% confidence
      interval, 0.3-5), hospital length of stay (11.2+1.3 vs. 9.5+0.8 days, p=.3), or
      nonroutine discharge (odds ratio, 1.1; 95% confidence interval, 0.5-2.2).
      CONCLUSIONS: Ground transport for interfacility transfer of patients with spinal
      injury appears to be safe and suitable for patients who lack other compelling
      reasons for HEMS. A prospective analysis of transportation mode in a larger
      cohort of patients is needed to verify our findings.

PMID- 24139233
TI  - Dose-response and efficacy of spinal manipulation for care of chronic low back
      pain: a randomized controlled trial.
AB  - BACKGROUND CONTEXT: There have been no full-scale trials of the optimal number of
      visits for the care of any condition with spinal manipulation. PURPOSE: To
      identify the dose-response relationship between visits to a chiropractor for
      spinal manipulation and chronic low back pain (cLBP) outcomes and to determine
      the efficacy of manipulation by comparison with a light massage control. STUDY
      DESIGN/SETTING: Practice-based randomized controlled trial. PATIENT SAMPLE: Four
      hundred participants with cLBP. OUTCOME MEASURES: The primary cLBP outcomes were
      the 100-point modified Von Korff pain intensity and functional disability scales
      evaluated at the 12- and 24-week primary end points. Secondary outcomes included
      days with pain and functional disability, pain unpleasantness, global perceived
      improvement, medication use, and general health status. METHODS: One hundred
      participants with cLBP were randomized to each of four dose levels of care: 0, 6,
      12, or 18 sessions of spinal manipulation from a chiropractor. Participants were
      treated three times per week for 6 weeks. At sessions when manipulation was not
      assigned, they received a focused light massage control. Covariate-adjusted
      linear dose effects and comparisons with the no-manipulation control group were
      evaluated at 6, 12, 18, 24, 39, and 52 weeks. RESULTS: For the primary outcomes,
      mean pain and disability improvement in the manipulation groups were 20 points by
      12 weeks and sustainable to 52 weeks. Linear dose-response effects were small,
      reaching about two points per six manipulation sessions at 12 and 52 weeks for
      both variables (p<.025). At 12 weeks, the greatest differences from the no
      manipulation control were found for 12 sessions (8.6 pain and 7.6 disability
      points, p<.025); at 24 weeks, differences were negligible; and at 52 weeks, the
      greatest group differences were seen for 18 visits (5.9 pain and 8.8 disability
      points, p<.025). CONCLUSIONS: The number of spinal manipulation visits had modest
      effects on cLBP outcomes above those of 18 hands-on visits to a chiropractor.
      Overall, 12 visits yielded the most favorable results but was not well
      distinguished from other dose levels.

PMID- 24139234
TI  - Baclofen for alcohol dependence in France: incidence of treated patients and
      prescription patterns--a cohort study.
AB  - Recently, baclofen has been widely promoted for treatment of alcohol dependence
      in France. Our aim was firstly to describe the incidence of patients newly
      treated with baclofen for alcohol dependence in France from 2007 to 2011, and
      secondly to describe baclofen prescription patterns and prescribers. A
      retrospective cohort study of patients newly treated with baclofen was conducted
      using the "Echantillon Generaliste des Beneficiaires" database (EGB). Patients
      with a first dispensation of baclofen between 01/01/2007 and 31/12/2011, followed
      by a second in the next 120 days, were included. Patients were considered treated
      with baclofen for neurological conditions if at least one of the following
      conditions was found to be true: (1) presence of a neurological condition for
      which baclofen could be prescribed, (2) dispensation of dantrolene, another anti
      spastic drug, or (3) hospitalization for a neurological condition for which
      baclofen could be prescribed. We assumed that all the remaining patients were
      treated for alcohol dependence. During the 5-year period, 676 patients were
      incident users. While the annual incidence rate of patients newly treated with
      baclofen for neurological conditions remained stable, the annual incidence rate
      of patients newly treated with baclofen for alcohol dependence increased by a
      factor of 2.9 between 2007 (0.09/1000 person-years) and 2011 (0.26/1000 person
      years). In the alcohol dependence group, median duration of baclofen treatment
      was 143.5 [74.0; 377.0] days; median daily dose was 24.4 [14.8; 39.5] mg. This
      study demonstrated the rapidly increasing use of baclofen in France for treatment
      of alcohol dependence. 

PMID- 24139235
TI  - Conditional survival after radical cystectomy for bladder cancer: evidence for a
      patient changing risk profile over time.
AB  - BACKGROUND: Standard survival statistics do not take into consideration the
      changes in the weight of individual variables at subsequent times after the
      diagnosis and initial treatment of bladder cancer. OBJECTIVE: To assess the
      changes in 5-yr conditional survival (CS) rates after radical cystectomy for
      bladder cancer and to determine how well-established prognostic factors evolve
      over time. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 8141 patients
      treated with radical cystectomy at 15 international academic centers between 1979
      and 2012. INTERVENTIONS: Radical cystectomy and pelvic lymph node dissection.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Conditional cancer-specific
      survival (CSS) and overall survival (OS) estimates were calculated using the
      Kaplan-Meier method. The multivariable Cox regression model was used to calculate
      proportional hazard ratios for the prediction of mortality after stratification
      by clinical characteristics (age, perioperative chemotherapy status) and
      pathologic characteristics (pT stage, grade, lymphovascular invasion, pN stage,
      number of nodes removed, margin status). The median follow-up was 32 mo. RESULTS
      AND LIMITATIONS: The 5-yr CSS and OS rates were 67.7% and 57.5%, respectively.
      Given a 1-, 2-, 3-, 5- and 10-yr survivorship, the 5-yr conditional OS rates
      improved by +5.6 (60.7%), +8.4 (65.8%), +7.6 (70.8%), +3.0 (72.9%), and +1.9%
      (74.3%), respectively. The 5-yr conditional CSS rates improved by +5.6 (71.5%),
      +9.8 (78.5%), +7.9 (84.7%), +7.2 (90.8%), and 5.6% (95.9%), respectively. The 5-
      and 10-yr CS improvement was primarily noted among surviving patients with
      advanced stage disease. The impact of pathologic parameters on CS estimates
      decreased over time for both CSS and OS. Findings were confirmed on multivariable
      analyses. The main limitation was the retrospective design. CONCLUSIONS: CS
      analysis demonstrates that the patient risk profile changes over time. The risk
      of mortality decreases with increasing survivorship. The CS rates improve mainly
      in the case of advanced stage disease. The impact of prognostic pathologic
      features decreases over time and can disappear for long-term CS.

PMID- 24139236
TI  - Effect of flutamide on folliculogenesis in the fetal porcine ovary--regulation by
      Kit ligand/c-Kit and IGF1/IGF1R systems.
AB  - In pigs, primordial to primary follicle transition occur in the late pregnancy.
      The interactions between Kit ligand (KL) and its receptor (c-Kit), as well as
      insulin-like growth factor 1 (IGF1) and cognate receptor (IGF1R) are crucial for
      the primordial follicle activation. It is well established that hormonal
      disruption induces abnormalities in the developing reproductive system. Hence,
      this study investigated the influence of antiandrogen, flutamide, on genes
      involved in the primordial to primary follicle transition. Pregnant gilts were
      injected with flutamide (50mg/kg bw, seven times, every day) or corn oil (control
      groups) starting on gestation days 83 (GD90) or 101 (GD108). Fetal ovaries were
      excised on days 90 and 108 of gestation. The proportion of primordial and primary
      follicles was determined, and immunohistochemistry for c-Kit and IGF1R was
      conducted. To assess KL, c-Kit, IGF1 and IGF1R mRNA expression real-time PCR was
      performed. Ovaries from both GD90 and GD108 animals exhibited a greater
      proportion of primordial to primary follicles when compared to respective control
      groups. C-Kit and IGF1R were immunolocalized in the oocytes of primordial and
      primary follicles. Both c-Kit mRNA and protein levels and KL mRNA expression were
      diminished in GD90 group. IGF1R expression decreased at mRNA and protein levels,
      whereas IGF1 mRNA expression was increased in GD90 and GD108 groups. In summary,
      our findings may indicate that the interactions between KL and c-Kit as well as
      IGF1 and IGF1R are relevant to the initiation of follicular transition from
      primordial into primary follicles and can be affected by AR signaling. 

PMID- 24139237
TI  - Expression regulation of co-inhibitory molecules on human natural killer cells in
      response to cytokine stimulations.
AB  - Co-inhibitory molecules have become the key targets in cancer immunotherapy with
      the strategy of blocking immune checkpoints to reverse the pathogenic regulation
      of T cells. However, their expression regulations in NK cells, the most important
      innate immune cells against tumor, remain largely undefined. In this study, we
      showed that the expressions of co-inhibitors on NK cells, including LAG-3, PD-1,
      and TIGIT, are differently regulated by cytokines IL-10, IL-12, IL-15, IFN-alpha,
      and TGF-beta. Among the tested cytokines, IL-12 is the most powerful inducer of
      LAG-3, and TGF-beta is the strongest suppresser of PD-1. Notably, the expression
      of these co-inhibitors responds to the time course of stimulus progressively.
      Together, these findings illustrated that the co-inhibitors on NK cells express
      differently in response to cytokine stimulations of IL-10, IL-12, IL-15, IFN
      alpha, and TGF-beta, providing an initial information on the expression
      regulation of co-inhibitors in human NK cells. 

PMID- 24139238
TI  - Genetic polymorphisms involved in the inflammatory response and lung cancer risk:
      a case-control study in Japan.
AB  - Evidence is accumulating that chronic inflammation may have an important
      mechanism for the development and progression of lung cancer. Therefore, genetic
      polymorphisms in genes that involved in the inflammatory response may be
      associated with lung cancer risk. We evaluated the role of tumor necrosis factor
      alpha (TNFA) rs1799724, interleukin 1beta (IL1B) rs16944, IL6 rs1800796,
      myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case
      control study comprised of 462 lung cancer cases and 379 controls in a Japanese
      population. Unconditional logistic regression was used to assess the adjusted
      odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR=1.64,
      95% CI=1.19-2.26) and IL6 rs1800796 (OR=1.41, 95% CI=1.02-1.96) were associated
      with lung cancer risk. In addition, we assessed interactions between the
      polymorphisms and smoking. The polymorphisms did not significantly modify the
      association between smoking and lung cancer. As TNFA triggers a cytokine cascade,
      the modifying effect of the TNFA rs1799724 genotypes on the association of any of
      the remaining polymorphisms with lung cancer risk was also examined. There was a
      significant interaction between TNFA rs1799724 and MPO rs2333227
      (Pinteraction=0.058). Future studies involving larger control and case
      populations will undoubtedly lead to a more thorough understanding of the role of
      the polymorphisms involved in the inflammation pathway in lung cancer. 

PMID- 24139239
TI  - Eryngial (trans-2-dodecenal), a bioactive compound from Eryngium foetidum: its
      identification, chemical isolation, characterization and comparison with
      ivermectin in vitro.
AB  - Methanol-water (4:1, v/v) crude extracts (50 mg mL(-1)) of 25 Jamaican medicinal
      plants were screened in vitro for anthelmintic activity using infective third
      stage larvae of Strongyloides stercoralis. The most effective extract was further
      chemically scrutinized to isolate and identify the source of the bioactivity, and
      the efficacy of this compound was compared with ivermectin. Eosin exclusion (0.1
      mg mL(-1)) served as the indicator of mortality in all bioassays. A crude extract
      of Eryngium foetidum (Apiaceae) was significantly (Probit Analysis, P<0.05) more
      potent than the other plant extracts, taking 18.9 h to kill 50% (LT50) of the
      larvae. Further, the petrol extract of E. foetidum was significantly more
      effective (Probit Analysis, P<0.05) at killing the larvae (LT50, 4.7 h) than
      either its methanol-water or dichloromethane extract. The latter two effected
      less than 1% larval mortality after 120 h. With bioassay-driven column
      chromatography of the petrol extract, trans-2-dodecenal (eryngial) was identified
      and chemically isolated as the main anthelmintic compound in E. foetidum. There
      was a significant difference between the 24 h LD50 values (mm) of trans-2
      dodecenal (0.461) and ivermectin (2.251) but there was none between the 48 h LD50
      values (mm): trans-2-dodecenal (0.411) and ivermectin (0.499) in vitro.

PMID- 24139240
TI  - Paraneoplastic opsoclonus myoclonus with autoantibodies to glutamic acid
      decarboxylase.

PMID- 24139241
TI  - [Reversible dementia: don't forget neurosarcoidosis!].

PMID- 24139242
TI  - [Occlusion of the artery of Percheron revealing a vasculo-Behcet].

PMID- 24139243
TI  - [Cavitary lesions in multiple sclerosis: multicenter study on twenty patients].
AB  - INTRODUCTION: Cavitary white matter changes are mainly described in
      leukodystrophies and especially in vanishing white matter disease. Large cavitary
      lesions are not typical for multiple sclerosis (MS). METHODS: We studied MS
      patients with large cavitary brain lesions. Patient characteristics, disease
      onset/duration/subtype, expanded disability status scale (EDSS), mini mental
      state (MMS), vanishing white matter disease genetic analysis, and MRI
      characteristics of the cavitary lesions were analyzed. RESULTS: Twenty patients
      were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17
      58). Mean disease duration was 10 years (range 2-20). Five patients had initial
      relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS
      was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic
      analysis was performed and negative in seven patients. Inferior corpus callosum
      lesions were seen in all patients with available sagittal FLAIR sequences.
      Cavitary lesions were strictly supratentorial, and located inside the diffuse
      leukoencephalopathy, with often a posterior predominance. CONCLUSION: MS patients
      with large cavitary lesions seem to represent a MS subgroup, predominantly women,
      with relatively late disease onset, predominantly primary-progressive type,
      relatively high EDSS scores, and severe cognitive dysfunction.

PMID- 24139244
TI  - [Progressive multifocal leukoencephalopathy and natalizumab-related immune
      reconstitution inflammatory syndrome: the advantage of MRI].

PMID- 24139245
TI  - [Nutritional status in patients with recurrent glioblastoma].
AB  - INTRODUCTION: Nutritional status is a major clinical parameter in multiple
      cancers. Indeed, nutritional status is a prognostic factor and a predictor of
      response and toxicity to treatments in breast and lung cancers for instance. To
      our knowledge, in patients suffering from malignant primary brain tumors,
      nutritional status has been poorly investigated. METHODS: Nutritional status of
      26 glioblastoma patients relapsing after a first line of treatment was studied.
      The body mass index (BMI), the prognostic inflammatory and nutritional index
      (PINI) and the instant nutritional score (INS) were assessed. RESULTS: The BMI
      was abnormal in 12 patients, two were malnourished while 10 were overweight. The
      BMI was not correlated to age of patients. Overweight status did not impact
      patient survival but it was associated with reduced performance status. The PINI
      was abnormal in three patients. Finally, the INS was abnormal in 24 patients,
      noted 2 (n=22) or 4 (n=4). CONCLUSIONS/DISCUSSION: Our results were not in favor
      of systematic nutritional support in patients with recurrent glioblastoma after a
      first line of treatment. Being overweight does not influence prognosis but may
      influence performance status. Steroid therapy and chemotherapy (inducing sodium
      and water retention and lymphopenia) weaken the relevance of BMI and INS for
      nutritional assessment in patients with recurrent glioblastoma. Further studies
      using additional nutritional tests in larger, independent and prospective cohorts
      of patients are warranted to obtain more details.

PMID- 24139246
TI  - Anticipated adaptation or scale recalibration?
AB  - BACKGROUND: The aim of our study was to investigate anticipated adaptation among
      patients in the subacute phase of Spinal Cord Injury (SCI). METHODS: We used an
      observational longitudinal design. Patients with SCI (N = 44) rated their actual,
      previous and expected future Quality of Life (QoL) at three time points: within
      two weeks of admission to the rehabilitation center (RC), a few weeks before
      discharge from the RC, and at least three months after discharge. We compared the
      expected future rating at the second time point with the actual ratings at the
      third time point, using student's t-tests. To gain insight into scale
      recalibration we also compared actual and previous ratings. RESULTS: At the group
      level, patients overpredicted their improvement on the VAS. Actual health at T3(M
      = 0.65, sd =0.20)) was significantly lower than the predicted health at T1 of T3
      (M = 0.76, sd = 0.1; t(43) = 3.24, p < 0.01), and at T2 of T3(M = 0.75,sd = 0.13;
      t(43) = 3.44, p < 0.001). Similarly the recalled health at T3 of T2 (M = 0.59, sd
      = 0.18) was significantly lower than the actual health at T2 (M = 0.67, sd =
      0.15; t(43) = 3.26, p <0.01). Patients rated their future and past health
      inaccurately compared to their actual ratings on the VAS. In contrast, on the TTO
      patients gave accurate estimates of their future and previous health, and they
      also accurately valued their previous health. Looking at individual ratings, the
      number of respondents with accurate estimates of their future and previous health
      were similar between the VAS and TTO. However, the Bland-Altman plots show that
      the deviation of the accuracy is larger for the TTO then the VAS. That is the
      accuracy of 95% of the respondents was lower in the TTO then in the VAS.
      CONCLUSIONS: Patients at the onset of a disability were able to anticipate
      adaptation. Valuations given on the VAS seem to be biased by scale recalibration.

PMID- 24139247
TI  - Adipose tissue and adipocyte dysregulation.
AB  - Obesity-associated insulin resistance is a complex disorder involving a number of
      candidate molecules, pathways and transduction systems possessing potential
      causal actions. Inflammation in adipose tissue (AT) is one mechanism proposed to
      explain the development of insulin resistance, while identification of factors
      that lead to or cause AT dysfunction when it reaches its limit of expansion
      represents an important challenge. Pathological expansion of AT is characterized
      by changes in its blood flow, and the presence of enlarged and dysfunctional
      adipocytes that begin an inflammatory campaign of altered adipokine and cytokine
      secretions. Adipocyte senescence, necrosis and death are associated with
      increased immune cell and macrophage infiltration of AT in obesity. This can
      boost inflammation and reinforce fat cell dysfunction and death. In addition,
      pathological fat mass expansion is also related to limited recruitment of fat
      cell progenitors able to proliferate and differentiate into healthy small fat
      cells to compensate for cell death and preserve adipocyte numbers. Limiting
      vascular development and enhancing fibrotic processes worsen inflammation towards
      chronic irreversibility. The AT expandability hypothesis states that failure of
      AT expansion is one of the key factors linking positive energy balance and
      cardiometabolic risks, not obesity per se. Besides the usual treatment of obesity
      based on behavioral approaches (specific dietary/nutritional approaches together
      with increased physical activity), a number of questions remain concerning the
      possible recovery of metabolic health after inflammation-preventing
      interventions. 

PMID- 24139249
TI  - Diagnostic accuracy of a clinical prediction rule (CPR) for identifying patients
      with recent-onset undifferentiated arthritis who are at a high risk of developing
      rheumatoid arthritis: a systematic review and meta-analysis.
AB  - OBJECTIVES: The Leiden clinical prediction rule (CPR) was developed in 2007 to
      predict disease progression in patients with recent-onset undifferentiated
      arthritis (UA). This systematic review and meta-analysis investigates the
      predictive ability of the rule at identifying patients who are at a high risk of
      developing rheumatoid arthritis (RA). METHODS: A systematic review of the
      literature search was conducted from 2007 to May 2013 to identify studies that
      validated the rule. This study adhered to the PRISMA guidelines. The
      methodological quality of studies was assessed using the QUADAS-2 tool. Pooled
      sensitivity and specificity values for each of the cut points were generated
      using a bivariate random-effects model. Heterogeneity was assessed using the
      variance of logit-transformed sensitivity and specificity. Bayes' theorem was
      used to calculate post-test probability of progression from UA to RA. RESULTS:
      The search identified four relevant studies, resulting in six data sets (n =
      1084). A cut point of >= 9 was identified as the optimal cut point for
      determining progression to RA. It is associated with a greater pooled specificity
      (0.99, 95% CI 0.95-1.00) than sensitivity (0.31, 95% CI 0.24-0.37). Using Bayes'
      theorem, a score of >= 9 points increased the pre-test probability from 40.04% to
      93.63%. A less stringent cut-off of >= 8 also identified a significant proportion
      of patients at risk of RA who have a high likelihood of progressing to RA (LR +
      9.5, 95% CI 6.21-14.54). CONCLUSION: A cut point of >= 9 offers an optimal
      estimate for identifying patients with UA who are at a high risk of developing RA
      and warrant intervention. However, a number of methodological limitations
      identified across studies suggest that the results should be interpreted
      cautiously and that further validation of the Leiden CPR is necessary.

PMID- 24139250
TI  - Buffered lidocaine for incision and drainage: a prospective, randomized double
      blind study.
AB  - INTRODUCTION: Buffered local anesthetics have not been studied for incision and
      drainage procedures in dentistry. The purpose of this prospective, randomized,
      double-blind study was to compare the pain of infiltration and pain of an
      incision and drainage procedure by using a buffered versus a nonbuffered 2%
      lidocaine with 1:100,000 epinephrine solution in symptomatic patients with a
      diagnosis of pulpal necrosis and associated acute swelling. METHODS: Eighty-one
      adult patients were randomly divided into 2 treatment groups who received 2
      infiltrations (mesial and distal to the swelling of the same formulation) by
      using either 2% lidocaine with 1:100,000 epinephrine buffered with 0.18 mL 8.4%
      sodium bicarbonate or 2% lidocaine with 1:100,000 epinephrine. Patients rated
      pain of needle insertion, placement, and solution deposition for each
      infiltration on a 170-mm visual analog scale. An incision and drainage procedure
      was performed, and the pain of incision, drainage, and dissection was recorded.
      RESULTS: No significant differences were found between the 2 anesthetic
      formulations for pain of solution deposition for either the mesial or distal site
      infiltrations. Moderate-to-severe pain was experienced in the majority of
      patients with the incision and drainage procedure. No significant differences
      were found between the 2 formulations. CONCLUSIONS: The addition of a sodium
      bicarbonate buffer to 2% lidocaine with 1:100,000 epinephrine did not result in
      significantly decreased pain of infiltrations or significantly decreased pain of
      the incision and drainage procedure when compared with 2% lidocaine with
      1:100,000 epinephrine in symptomatic patients with a diagnosis of pulpal necrosis
      and associated acute swelling.

PMID- 24139251
TI  - A practice-based study on the survival of restored endodontically treated teeth.
AB  - INTRODUCTION: This retrospective study evaluated the survival of endodontically
      treated teeth (ETTs) and investigated factors influencing restoration and tooth
      survival. METHODS: Data from 795 ETTs were recorded, and success (restoration
      still intact) and survival (restoration intact or failed/repaired/replaced and
      tooth still in situ) were analyzed using Kaplan-Meier statistics. A multivariate
      Cox regression analysis was performed to assess the variables influencing success
      and survival. RESULTS: At the end of the observation period (mean observation
      time = 4.48 years), 45 teeth had been extracted (annual failure rate for survival
      = 1.9% at 9.6 years) and 114 restorations had received a restorative follow-up
      treatment (annual failure rate for success = 4.9% at 9.6 years). CONCLUSIONS:
      ETTs showed acceptable survival and success in the long-term. Variables showing
      significant influence on survival were the number of teeth in the dentition and
      the presence of decay at the moment the patient entered the practice.

PMID- 24139252
TI  - The influence of bone tissue deficiency on the outcome of endodontic
      microsurgery: a prospective study.
AB  - INTRODUCTION: This study assessed the influence of deficiencies of the periapical
      and marginal bone tissue on clinical outcomes after endodontic microsurgery.
      METHODS: Data were collected from the Microscope Center of the Department of
      Conservative Dentistry at the Dental College of Yonsei University, Seoul, South
      Korea, between August 2004 and March 2011. In total, 199 teeth that required
      endodontic surgery were included in the study. During the surgical procedure,
      deficiencies of the periapical and marginal bone tissue were measured immediately
      before the flap was repositioned. The patients were recalled 6 months and 1 year
      after the surgical procedure to assess the clinical and radiographic signs of
      healing. The Student's t test or the Mann-Whitney U test and logistic regression
      were performed to evaluate the parameters. Significant associations between the
      outcome and all the evaluation parameters were analyzed using the Pearson chi
      square test or the Fisher's exact test with a significance level of 0.05.
      RESULTS: A recall rate of 67.8% (135/199 teeth) was obtained. The height of the
      buccal bone plate was the only significant predictor (P = .040) of the healing
      outcome, suggesting that teeth with a buccal bone plate >3 mm presented a higher
      success rate than teeth with a buccal bone plate that was <=3 mm high (94.3% vs
      68.8%, P < .001). CONCLUSIONS: These data suggest that a favorable prognosis can
      be expected when teeth are covered with a buccal bone plate that is >3 mm in
      height regardless of the amount of marginal bone loss.

PMID- 24139253
TI  - Retrospective evaluation of perforation repairs in 6 private practices.
AB  - INTRODUCTION: The purpose of this study was to investigate retrospectively the
      clinical outcome of 70 perforation repairs performed by 6 endodontic specialists.
      METHODS: Endodontic specialists performed a total of 70 perforation repairs (69
      patients) between 1998 and 2010 using a nonsurgical or combined
      nonsurgical/surgical approach. Treatments were performed with the aid of a dental
      operating microscope. Recalls of at least 6 months were obtained on 49 patients
      (50 teeth). Two calibrated observers evaluated the radiographic results on
      recalls up to 116 months, with a mean of 37 months. Pre-, intra-, and
      postoperative data were evaluated with respect to treatment outcomes and possible
      prognostic factors. RESULTS: Successful results were obtained in 45 of 50
      perforation repairs, a success rate of 90%. Significant prognostic factors
      included the location of the perforation, sex of the patient, and restorative
      status of the tooth before perforation repair. The overall success rate of this
      study was higher than reported in other studies. CONCLUSIONS: Perforation repairs
      can be performed with a high level of success at least in the short- to medium
      term.

PMID- 24139254
TI  - In vivo quantitative evaluation of live and dead bacteria in root canal infection
      by using propidium monoazide with real-time PCR.
AB  - INTRODUCTION: For selective detection of viable bacteria with molecular methods,
      propidium monoazide (PMA) treatment has been successfully applied to a wide range
      of bacteria. The purpose of this study was to compare the quantity of live cells
      with the total amounts of both live and dead cells before and after
      chemomechanical preparation by using PMA in combination with real-time polymerase
      chain reaction (qPCR). METHODS: Twenty-one teeth with pulp necrosis and a
      periapical lesion were included. Bacterial sampling of the root canals was
      performed before (S1) and after (S2) chemomechanical root canal treatment. Each
      sample was separated into 2 different tubes. PMA was added to one of the tubes,
      and the other was left untreated. Then, DNA extraction and qPCR were performed.
      To evaluate the validity of the PMA treatment, the defined mixtures containing
      different ratios of live and dead cell suspensions of Enterococcus faecalis were
      either subjected to PMA treatment or not subjected to PMA treatment, followed by
      qPCR quantification. RESULTS: A paired t test showed a highly significant
      difference in the mean threshold cycle values between S1 with and without PMA (P
      = .0002), and this difference (0.89) was similar to that (0.96) obtained from the
      samples consisting of 80% live cell suspension and 20% dead cell suspension of E.
      faecalis. The threshold cycle values between the S2 samples with and without PMA
      were also significantly different (P = .0134), and this difference (0.37) was
      similar to that obtained from the 100% live cell suspension of E. faecalis
      (0.42). CONCLUSIONS: PMA in conjunction with qPCR appeared to be useful in
      analyzing the primary infections of root canals because there were significant
      amounts of dead bacteria in the root canals. Although the use of PMA treatment in
      post-preparation samples significantly reduced the detection of dead bacteria,
      this difference was still small, so further studies should be carried out to
      confirm the necessity of PMA treatment.

PMID- 24139255
TI  - Treatment outcome after repair of root perforations with mineral trioxide
      aggregate: a retrospective evaluation of 90 teeth.
AB  - INTRODUCTION: In this retrospective study, the success rate for the repair of
      root perforations using mineral trioxide aggregate was investigated. METHODS: One
      hundred forty consecutive cases of teeth with perforations were included in the
      sample; 128 finally met the inclusion criteria. All treatments were performed
      between 1999 and 2009 in a dental office limited to endodontics. Perforations
      were sealed with mineral trioxide aggregate using a dental operating microscope.
      Treatment success was assessed by analyzing clinical data and radiographs 1-10
      years after treatment. The radiographs were evaluated by 2 independent calibrated
      examiners. The outcome measure was dichotomized as "healed" or "failure." The
      relationship between preoperative data and treatment outcome was examined to
      determine potential prognostic factors. RESULTS: From 128 teeth, 90 were
      accessible for recall (70.3%). The mean follow-up interval was 3.4 years. Sixty
      six teeth (73.3%) were classified as healed. A significant relationship between
      treatment success and the presence of a preoperative lesion at the perforation
      site was found. Those teeth in which a lesion at the perforation site was present
      before treatment showed a lower healing rate. Teeth with a preoperative
      communication between the perforation and the oral cavity showed the lowest
      success rate. CONCLUSIONS: Two prognostic factors for healing of teeth with
      perforations were identified. The presence of a preoperative lesion at the
      perforation site and direct contact between the perforation and the oral cavity
      were related to lower treatment success rates.

PMID- 24139256
TI  - A new method of topical anesthesia by using anesthetic solution in a patch.
AB  - INTRODUCTION: We investigated the effects of topical anesthesia of the oral
      mucosa by using an adhesive patch instilled with 2% lidocaine hydrochloride
      solution. METHODS: The subjects were 20 healthy adult volunteers who gave written
      informed consent. Each patient was treated in a randomized crossover fashion with
      a hemostatic adhesive patch instilled with one of the following agents: 2%
      lidocaine hydrochloride with 12.5 MUg/mL epinephrine, 2% lidocaine hydrochloride,
      20% ethyl aminobenzoate, or physiological saline solution. A cotton ball
      containing 20% ethyl aminobenzoate was also tested. The adhesive patch or cotton
      ball was placed on the gingivobuccal fold of the maxillary right canine for 2 or
      5 minutes. Then, a 33-gauge or 30-gauge needle was inserted to a depth of 2 mm.
      Insertion pain was evaluated with a visual analog scale (VAS) and a 4-level
      verbal rating scale immediately after needle removal. Efficacy of analgesia was
      calculated from the verbal rating scale. RESULTS: The VAS was lower and the
      efficacy of analgesia was higher on 33-gauge needle insertion than on 30-gauge
      needle insertion in all treatments. The VAS was also significantly lower and the
      efficacy of analgesia was higher in the lidocaine groups than in the other
      groups. Adding epinephrine did not enhance the anesthetic effect of lidocaine
      hydrochloride. CONCLUSIONS: Topical mucosal anesthesia with an adhesive patch
      containing 2% lidocaine hydrochloride solution is simple and may be more
      effective than conventional methods.

PMID- 24139257
TI  - An anatomic investigation of the mandibular first molar using micro-computed
      tomography.
AB  - INTRODUCTION: The mandibular first molar is the most frequently endodontically
      treated tooth and is extremely anatomically challenging. The purpose of this
      micro-computed tomographic evaluation was to quantitatively investigate the
      morphology of the mandibular first molar to improve both orthograde and
      retrograde treatment. METHODS: Twenty-two mandibular first molars were scanned,
      reconstructed, and subjected to various linear measurements. The average,
      standard deviation, and standard error of the mean of each linear measurement
      were calculated, and the mode for each nominal data category was determined.
      RESULTS/CONCLUSIONS: The furcal aspect of the entire mesial root should be
      considered a "danger zone." Mesial canals were found to be much more variable
      than distal canals in morphology, whereas the relative position of the orifices
      of the mesial canals was relatively consistent at 1.5 mm from the pulpal floor.
      Root-end resection of 3 mm would remove the majority of lateral canals and apical
      ramifications.

PMID- 24139258
TI  - The presence of autophagy in human periapical lesions.
AB  - INTRODUCTION: Autophagy, a lysosome- or endosome-mediated self-degradation
      process, participates in diverse neurodegenerative diseases, cancer, and
      inflammatory diseases associated with apoptosis. This study aims to identify the
      presence of autophagy in human periapical lesions and its possible colocalization
      with apoptosis. METHODS: Forty-seven samples of human periapical lesions
      diagnosed as radicular cysts (RCs, n = 23) or periapical granulomas (PG, n = 24)
      were examined. The inflammatory infiltrates of lesions were evaluated by
      hematoxylin-eosin staining, and the presence of autophagy was analyzed by
      immunohistochemistry using the autophagic marker LC3 antibody. Immunofluorescence
      and deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)
      double labeling was performed to colocalize LC3 with the apoptotic TUNEL signal.
      Transmission electron microscopy was conducted to assess the presence of
      autophagy. RESULTS: LC3 was detected in all samples of RCs and PGs, but it was
      sparse in healthy dental pulp tissues. Macrophages, lymphocytes,
      polymorphonuclear leukocytes, and endothelial cells were stained positive for LC3
      in both types of lesions. Epithelial cells were also stained positive for LC3 in
      RCs. Quantitative analysis revealed that LC3 expression in RCs is significantly
      greater than that in PGs. Immunofluorescence and TUNEL double-labeling analysis
      revealed that LC3 was partially colocalized with the TUNEL signal in both RCs and
      PGs. Furthermore, transmission electron microscopy confirmed the presence of
      autophagy and their partial colocalization with apoptotic nucleus at the
      ultrastructural level. CONCLUSIONS: Our findings indicate that autophagy is
      present in clinical periapical lesions, which is partially associated with
      apoptosis.

PMID- 24139259
TI  - Effectiveness of antibiotic medicaments against biofilm formation of Enterococcus
      faecalis and Porphyromonas gingivalis.
AB  - INTRODUCTION: In this study we compared the antibacterial effect of triple
      antibiotic paste (TAP), double antibiotic paste (DAP), and calcium hydroxide
      [Ca(OH)2] against Enterococcus faecalis and Porphyromonas gingivalis biofilm.
      METHODS: The minimum inhibitory concentration (MIC), minimum bactericidal
      concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and biofilm
      formation were measured by using microtiter plate methods. The 2 bacteria were
      treated with different dilutions of TAP, DAP, and Ca(OH)2 solutions. The
      turbidities of the bacterial cultures in the microtiter plate were measured by
      optical density at 490 nm by using a spectrophotometer. Data were analyzed by 2
      way analysis of variance (alpha = 0.05). RESULTS: For TAP, the MIC and MBIC
      values were 0.003 mg/mL for E. faecalis and 0.006 mg/mL for P. gingivalis. The
      MBC values for TAP were 0.3 mg/mL for both bacteria. The MIC and MBIC values for
      DAP were 0.001 mg/mL for E. faecalis and P. gingivalis. The MBC values for DAP
      were 0.14 mg/mL for both bacteria. Biofilm formation of the 2 bacteria was
      significantly decreased with TAP and DAP at all tested dilutions (P < .0001)
      compared with control groups; however, TAP and DAP biofilm formations were not
      significantly different from each other. Ca(OH)2 significantly decreased
      bacterial biofilm formation compared with the control, but it was significantly
      less than TAP and DAP (P < .05). CONCLUSIONS: Both TAP and DAP were more
      effective than Ca(OH)2 against E. faecalis and P. gingivalis. DAP can be
      considered an effective and comparable antibacterial substitute for TAP.

PMID- 24139260
TI  - Absent in melanoma 2 (AIM2) in rat dental pulp mediates the inflammatory response
      during pulpitis.
AB  - INTRODUCTION: In recent years, the inflammasome has been determined to play an
      important role in inflammatory diseases. However, the role of the inflammasome in
      pulpitis remains unclear. Absent in melanoma 2 (AIM2) is a type of inflammasome
      that recognizes cytosolic double stranded DNA and forms a caspase-1-activating
      inflammasome with apoptosis-associated speck-like protein containing a caspase
      activating recruiting domain. In this study, we determined whether AIM2 was
      expressed in pulp cells and defined the role of AIM2 in the initiation of
      inflammation within the dental pulp. METHODS: In the in vivo study, the right
      maxillary molars from male adult Sprague-Dawley rats (250-350 g) were exposed to
      the pulp. In the in vitro study, the pulp cells isolated from the mandibular
      incisors of the Sprague-Dawley rats (2 weeks) were conventionally cultured.
      Immunofluorescence staining was used to determine the expression and distribution
      of AIM2 in the rat dental pulp tissues and cells in the presence or absence of
      inflammatory stimulation. Western blotting and real-time polymerase chain
      reaction were performed to determine whether there was a correlation between AIM2
      expression levels and inflammation both in vivo and in vitro. RESULTS: In healthy
      dental pulp tissues and cells, AIM2 was only detected in the odontoblast layer.
      Stimulation significantly increased AIM2 expression in both the dental pulp
      tissues and cultured cells. The mRNA and protein levels of AIM2 were
      significantly up-regulated in response to inflammatory stimulation in a dose
      dependent manner. Moreover, we also found that AIM2 expression correlated with
      interleukin-1 levels. These results reveal a direct relationship between the AIM2
      inflammasome and pulpitis. CONCLUSIONS: Our study demonstrates that AIM2 is
      expressed in dental pulp tissues and mediates the inflammatory response during
      pulpitis. Therapeutic interventions aimed at reducing AIM2 expression may be
      beneficial in the treatment of pulpitis.

PMID- 24139261
TI  - Effect of smear layer against disinfection protocols on Enterococcus faecalis
      infected dentin.
AB  - INTRODUCTION: This study examined the effect of the smear layer on the
      antibacterial effect of different disinfecting solutions in infected dentinal
      tubules. METHODS: Cells of Enterococcus faecalis were forced into dentinal
      tubules according to a previously established protocol. After a 3-week incubation
      period of infected dentin blocks, a uniform smear layer was produced. Forty
      infected dentin specimens were prepared and subjected to 3 and 10 minutes of
      exposure to disinfecting solutions including sterile water, 2% and 6% sodium
      hypochlorite (NaOCl), 2% chlorhexidine (CHX), 17% EDTA, and QMiX (Dentsply Tulsa
      Dental, Tulsa, OK). The following combinations were also included: 2% NaOCl + 2%
      CHX, 2% NaOCl + QMiX, 6% NaOCl + QMiX, and 6% NaOCl + 17% EDTA + 2% CHX. Four
      other dentin specimens similarly infected but with no smear layer were subjected
      to 3 minutes of exposure to 2% CHX and 6% NaOCl for comparison. Confocal laser
      scanning microscopy and viability staining were used to analyze the proportions
      of dead and live bacteria inside the dentin. RESULTS: In the presence of a smear
      layer, 10 minutes of exposure to QMiX, 2% NaOCl + QMiX, 6% NaOCl + QMiX, and 6%
      NaOCl + 17% EDTA + 2% CHX resulted in significantly more dead bacteria than 3
      minutes of exposure to these same disinfecting solutions (P < .05). No
      statistically significant difference between 3 and 10 minutes was found in other
      groups (P > .05); 6% NaOCl + QMiX and 6% NaOCl + 17% EDTA + 2% CHX showed the
      strongest antibacterial effect. In the absence of a smear layer, 2% CHX and 6%
      NaOCl killed significantly more bacteria than they did in the presence of a smear
      layer (P < .05). CONCLUSIONS: The smear layer reduces the effectiveness of
      disinfecting agents against E. faecalis in infected dentin. Solutions containing
      6% NaOCl and/or QMiX showed the highest antibacterial activity.

PMID- 24139262
TI  - Davallialactone reduces inflammation and repairs dentinogenesis on glucose
      oxidase-induced stress in dental pulp cells.
AB  - INTRODUCTION: The chronic nature of diabetes mellitus (DM) raises the risk of
      oral complication diseases. In general, DM causes oxidative stress to organs.
      This study aimed to evaluate the cellular change of dental pulp cells against
      glucose oxidative stress by glucose oxidase with a high glucose state. The
      purpose of this study was to test the antioxidant character of davallialactone
      and to reduce the pathogenesis of dental pulp cells against glucose oxidative
      stress. METHODS: The glucose oxidase with a high glucose concentration was tested
      for hydroxy peroxide (H2O2) production, cellular toxicity, reactive oxygen
      species (ROS) formation, induction of inflammatory molecules and disturbance of
      dentin mineralization in human dental pulp cells. The anti-oxidant effect of
      Davallilactone was investigated to restore dental pulp cells' vitality and dentin
      mineralization via reduction of H2O2 production, cellular toxicity, ROS formation
      and inflammatory molecules. RESULTS: The treatment of glucose oxidase with a high
      glucose concentration increased H2O2 production, cellular toxicity, and
      inflammatory molecules and disturbed dentin mineralization by reducing pulp cell
      activity. However, davallialactone reduced H2O2 production, cellular toxicity,
      ROS formation, inflammatory molecules, and dentin mineralization disturbances
      even with a long-term glucose oxidative stress state. CONCLUSIONS: The results of
      this study imply that the development of oral complications is related to the
      irreversible damage of dental pulp cells by DM-induced oxidative stress.
      Davallialactone, a natural antioxidant, may be useful to treat complicated oral
      disease, representing an improvement for pulp vital therapy.

PMID- 24139263
TI  - Epigallocatechin-3-gallate blocks triethylene glycol dimethacrylate-induced
      cyclooxygenase-2 expression by suppressing extracellular signal-regulated kinase
      in human dental pulp and embryonic palatal mesenchymal cells.
AB  - INTRODUCTION: Methacrylate resin-based materials could release components into
      adjacent environment even after polymerization. The major components leached
      include triethylene glycol dimethacrylate (TEGDMA). TEGDMA has been shown to
      induce the expression of cyclooxygenase-2 (COX-2). However, the mechanisms are
      not completely understood. The aims of this study were to investigate the
      molecular mechanism underlying TEGDMA-induced COX-2 in 2 oral cell types, the
      primary culture of human dental pulp (HDP) cells and the human embryonic palatal
      mesenchymal (HEPM) pre-osteoblasts, and to propose potential strategy to prevent
      or ameliorate the TEGDMA-induced inflammation in oral tissues. METHODS: TEGDMA
      induced COX-2 expression and its signaling pathways were assessed by Western blot
      analyses in HDP and HEPM cells. The inhibition of TEGDMA-induced COX-2 protein
      expression using various dietary phytochemicals was investigated. RESULTS: COX-2
      protein expression was increased after exposure to TEGDMA at concentrations as
      low as 5 MUmol/L. TEGDMA-induced COX-2 expression was associated with reaction
      oxygen species, the extracellular signal-regulated kinase 1/2, and the p38
      mitogen-activated protein kinase signaling pathways in HDP and HEPM cells. The
      activation of p38 mitogen-activated protein kinase was directly associated with
      reactive oxygen species. Epigallocatechin-3-gallate suppressed TEGDMA-induced COX
      2 expression by inhibiting phosphorylation of extracellular signal-regulated
      kinase 1/2. CONCLUSIONS: Cells exposed to low concentrations of TEGDMA may induce
      inflammatory responses of the adjacent tissues, and this should be taken into
      consideration during common dental practice. Green tea, which has a long history
      of safe beverage consumption, may be a useful agent for the prevention or
      treatment of TEGDMA-induced inflammation in oral tissues.

PMID- 24139264
TI  - Antimicrobial substantivity of alexidine and chlorhexidine in dentin.
AB  - INTRODUCTION: The use of irrigating solutions with long-lived activity helps to
      avoid failure of endodontic therapy. The aim of the present study was to evaluate
      and compare the antimicrobial substantivity against Enterococcus faecalis by
      using as carrier a dentin-volumetric unit exposed to chlorhexidine (CHX) and
      alexidine (ALX). METHODS: Standardized dentin blocks of human molars were treated
      for 1 minute with 0.5% CHX, 2% CHX, 1% ALX, and 2% ALX. They were exposed to E.
      faecalis in suspension to determine antimicrobial substantivity during a period
      of 80 days. Results were analyzed by means of Kaplan-Meier survival analysis (P <
      .05). RESULTS: ALX obtained the best results, with differences that were
      significantly different from CHX regardless of the concentration. Although all
      the samples treated with CHX were contaminated at the end of the study period, a
      direct relationship was seen between concentration and survival time. There was
      no statistically significant difference between 2% and 1% ALX. CONCLUSIONS: The
      present study shows that 2% and 1% ALX used for 1 minute provide longer
      antimicrobial substantivity against E. faecalis than CHX when applied to 2% and
      0.5%.

PMID- 24139265
TI  - Human stem cells from the apical papilla response to bacterial lipopolysaccharide
      exposure and anti-inflammatory effects of nuclear factor I C.
AB  - INTRODUCTION: Stem cells from the apical papilla (SCAPs) are important for tooth
      root development and may be candidates for regenerative endodontic procedures
      involving immature teeth. The potential use of SCAPs for clinical applications
      requires a better understanding of their responses to bacterial challenge. We
      have investigated the effects of exposure of these cells to lipopolysaccharide
      (LPS). Inflammatory responses arising from bacterial challenges can constrain
      postinjury tissue regeneration and the effects of nuclear factor I C (NFIC),
      which plays a critical role in tooth root development. NFIC has been explored for
      its anti-inflammatory action in the context of endodontic treatment of immature
      teeth where continued root development is an important outcome. METHODS: SCAPs
      were exposed to LPS, and the expression of Toll-like receptor-4 (TLR4),
      interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF-alpha) were assessed by
      real-time polymerase chain reaction (RT-PCR). The pLenti6.3/v5-NFIC plasmid
      encoding the full-length NFIC or NFIC silencing by si-RNA (small interfering RNA)
      in SCAPs were measured by Western blotting or RT-PCR; the effects of NFIC on IL
      6, IL-8, and TNF-alpha were analyzed by RT-PCR. The protein levels were
      subsequently measured by enzyme-linked immunoassay. RESULTS: LPS induced the
      synthesis of IL-6, IL-8, and TNF-alpha in SCAPs in a time-dependent manner.
      Pretreatment with a TLR4 inhibitor significantly inhibited LPS-induced IL-6, IL
      8, and TNF-alpha expression. Knockdown of NFIC increased the expression of IL-6,
      IL-8, and TNF-alpha, whereas the overexpression of NFIC resulted in the
      suppression of the inflammatory response stimulated by 1 MUg/mL LPS, especially
      for IL-8. Together, these data show that LPS is recognized by the transmembranous
      receptor TLR4 to mediate inflammatory responses in SCAPs and NFIC overexpression
      can suppress LPS-initiated innate immune responses. CONCLUSIONS: The anti
      inflammatory effects of NFIC overexpression provide a valuable target to dampen
      inflammatory responses in the infected pulp to allow tissue regeneration to
      occur.

PMID- 24139266
TI  - Effect of post length and type of luting agent on the dislodging time of metallic
      prefabricated posts by using ultrasonic vibration.
AB  - INTRODUCTION: The purpose of this study was to determine and compare the times
      needed to dislodge prefabricated titanium posts of different luting lengths with
      various cements. METHODS: Eighty-one intact extracted, single-canal human teeth
      were selected and endodontically treated. Specimens were randomly divided into 9
      groups, which were arranged according to the post space length (5, 7, and 9 mm)
      and cement type (zinc phosphate, glass ionomer, and resin cement). Titanium posts
      were cemented into the post spaces, and after 1 week of storage they were
      subjected to ultrasonic vibration. The dislodging times were recorded and
      analyzed by using the Kruskal-Wallis and Mann-Whitney tests (P < .05). RESULTS: A
      significant difference was observed between the dislodging times on the basis of
      post length and luting agent (P < .001). There were also significant differences
      between different cements luted with the same length posts (P < .001).
      Significant differences were observed between the 5-mm posts and both the 7- and
      9-mm posts for each cement, but the differences between the 7-mm and 9-mm posts
      were not significant (P < .05). CONCLUSIONS: Changes in the cement type and post
      length alter the time required to dislodge a post with an ultrasonic device.

PMID- 24139267
TI  - Effect of photoactivated disinfection on bond strength of root canal filling.
AB  - INTRODUCTION: The aim of this in vitro study was to assess and compare the effect
      of photoactivated disinfection (PAD) on the bond strength of root canal sealers
      to human root canal dentin using the push-out test. METHODS: Fifteen extracted
      human mandibular premolar teeth with single and straight roots were used. After
      the clinical crowns were removed from the cementoenamel junction, root canals
      were prepared with the ProTaper (Dentsply Maillefer, Ballaigues, Switzerland)
      rotary system to the size of the F3 file. The smear layer of the roots was
      removed using 17% EDTA followed by 5.25% sodium hypochlorite (NaOCl) and
      distillate water. The roots were then randomly divided into 3 groups (n = 5)
      according to the final irrigation regimen. In group 1, PAD (FotoSan; CMS Dental,
      Copenhagen, Denmark) was applied to the root canals and light cured for 20
      seconds. Group 2 was finally irrigated with a 2% solution of chlorhexidine
      gluconate, and group 3 served as the control group (NaOCl + EDTA). All the canals
      were then obturated with the lateral condensation technique using gutta-percha
      and AH Plus sealer (Dentsply Maillefer) sealer. One-millimeter-thick horizontal
      sections from the coronal and midthirds of each root (n: 5 * 4 = 20) were sliced
      for the push-out bond strength measurement. The data were converted to
      megapascals and statistically analyzed using 1-way analysis of variance and the
      post hoc Tukey test. RESULTS: There was no significant difference among the bond
      strength of PAD, chlorhexidine gluconate, and NaOCl (P > .05). CONCLUSIONS: We
      conclude that PAD does not adversely affect the bond strength of the AH Plus
      sealer to root canal dentin and that it can be used for the final disinfection of
      root canals.

PMID- 24139268
TI  - Evaluation of a simplified fiber post removal system.
AB  - INTRODUCTION: This study investigated the influence of clinical experience in
      relation to the efficacy and effectiveness of removal of 2 different fiber posts.
      METHODS: In total, 48 intact single-rooted teeth were treated endodontically and
      obturated. Then, 10-mm post spaces were prepared, and fiber posts were luted.
      Twenty-four #1 D.T. Light-Posts were used in group 1, and 24 #2 Hi-Rem Prosthetic
      Posts were used in group 2. A pullout test (n = 8 per group) was performed by
      using a universal testing machine to compare bond strength. Then, fiber post
      removal efficacy and efficiency were tested. Each group was divided into 2
      subgroups (n = 8) according to operator experience. In group 1, fiber posts were
      removed with an ultrasonic handpiece by using a #3 Start-X tip. In group 2, a
      size 25/0.04 ProFile was used to remove the central soft polymer macrofiber, and
      a #2 Largo drill was used to remove the fiber post and luting cement remnants.
      Post removal times were recorded to evaluate efficacy. Weight change was
      determined, and post space walls were analyzed microscopically to evaluate
      effectiveness. RESULTS: Bond strength did not differ significantly (P = .7569)
      between post systems. Post hoc Tukey tests indicated that removal time was
      affected significantly by operator experience in group 1 (P < .001) but not in
      group 2. Weight change was affected significantly by experience level in both
      groups. No difference in post space wall characteristics was observed between
      subgroups. CONCLUSIONS: The Hi-Rem post was easier to remove than the D.T Light
      Post.

PMID- 24139269
TI  - In vitro fracture resistance of endodontically treated roots filled with a bonded
      filling material or different types of posts.
AB  - AIM: This study aimed to compare the fracture resistance of roots filled with a
      bonded material, fiber posts, or titanium post systems. METHODS: Canals in the
      first group were filled with AH Plus and gutta-percha cones, and roots in the
      second group were filled with Epiphany sealer and Resilon cones. The root
      fillings (60 roots) were removed up to 4 mm from the canal apex to obtain 10-mm
      deep post spaces, and posts were cemented. The groups were as follows: AH Plus
      control group, Epiphany control group, AH Plus fiber post group, AH Plus titanium
      post group, Epiphany fiber post group, and Epiphany titanium post group. Fracture
      tests were performed by using an Instron testing machine. The force was applied
      at a 45 degrees  axial angle with a constant speed of 1 mm/min. For each sample,
      the force at which fracture occurred was recorded in units of newtons.
      Statistical analysis was carried out by using analysis of variance test. RESULTS:
      There was no statistically significant difference between all groups (P > .05).
      CONCLUSIONS: Titanium posts, fiber posts, and Epiphany root canal filling systems
      were found to have no reinforcing effect on endodontically treated roots.

PMID- 24139270
TI  - Effect of modified nonequilibrium plasma with chlorhexidine digluconate against
      endodontic biofilms in vitro.
AB  - INTRODUCTION: Nonequilibrium plasma has been reported to effectively kill
      Enterococcus faecalis in endodontic biofilm compared with chlorhexidine
      digluconate (CHX). The purpose of this study was to evaluate the antimicrobial in
      vitro activity of modified nonequilibrium plasma with CHX against E. faecalis and
      multispecies biofilms on bovine dentin discs. METHODS: Sterile bovine dentin
      discs were incubated with E. faecalis or a mixture of bacteria from human dental
      root canal infections to form 1- and 3-week-old biofilms. The specimens were
      subjected to nonequilibrium plasma, modified nonequilibrium plasma with CHX, and
      2% CHX for 2- and 5-minute exposure. After treatment, the biofilms were stained
      with viability dyes and examined by confocal laser scanning microscopy and 3
      dimensional reconstruction analysis. The proportions of bacterial cells killed by
      the treatments were calculated. RESULTS: The 3-dimensional reconstruction images
      showed that 1- and 3-week-old biofilms adhered to bovine dentin discs. The
      proportions of dead cells increased significantly with the longer exposure in
      each treatment group (P < .05). Modified nonequilibrium plasma was the most
      effective in killing bacteria in E. faecalis and multispecies biofilms at both 2
      and 5 minutes (P < .05). No significant difference was detected between
      nonequilibrium plasma and CHX groups (P > .05). Significantly more cells were
      killed in 1-week-old biofilms than in 3-week-old biofilms in all groups (P <
      .05). CONCLUSIONS: The modified nonequilibrium plasma killed more bacteria than
      conventional nonequilibrium plasma and 2% CHX in E. faecalis and multispecies
      endodontic biofilms in vitro and thus shows promise as an additional tool in
      infection control during endodontic treatment.

PMID- 24139271
TI  - Comparison of the mechanical behavior between controlled memory and superelastic
      nickel-titanium files via finite element analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate the flexibility and torsional
      stiffness of a controlled memory (CM) nickel-titanium (NiTi) file and compare its
      mechanical responses with those of a superelastic NiTi file with the same
      geometry using finite element simulation. METHODS: A commercially available
      instrument with a tip size of 30 and a 0.06 taper was selected for this study.
      The geometric model for finite element analysis was generated by micro-computed
      tomographic scanning, and the data for the constitutive model of controlled
      memory NiTi were obtained from the literature. The numeric analysis was performed
      in ABAQUS (SIMULIA, Providence, RI) with boundary conditions that were based on
      the ISO 3630-1 specification. RESULTS: The CM NiTi file exhibited the least
      bending moment and maximum stress value (523 MPa) under 45 degrees  bending
      simulation. However, the least torsional stiffness was calculated for this same
      instrument. CONCLUSIONS: The higher flexibility and potential fatigue resistance
      of the CM NiTi files were confirmed, indicating that this new technology
      represents an improvement in the mechanical behavior of the rotary NiTi files.

PMID- 24139272
TI  - Effect of nano silica on setting time and physical properties of mineral trioxide
      aggregate.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) has been widely used in all fields
      of endodontics. One of the major drawbacks of this material is the long setting
      time. MTA is primarily composed of type 1 Portland cement and bismuth oxide. In
      cement, nanoscale SiO2 behaves as a filler to improve microstructure and to
      accelerate hydration process. The aforementioned reaction is also expected in MTA
      because of the same structure. Thus, the aim of this study was to evaluate the
      effect of addition of nano-SiO2 to MTA on the setting time and its physical
      properties. METHODS: Two concentrations (8% and 10%) of nano-SiO2 were added to
      the white MTA powder. After mixing with water, the setting time, compressive
      strength, and flexural strength were investigated and compared with pure MTA.
      RESULTS: With the addition of 8% and 10% of nano-SiO2 to the MTA, the setting
      time of both mixtures decreased significantly (P < .05). However, the compressive
      strength (after 1 day and 1 week) and flexural strength increased; this was not
      significant (P > .05). There was no significant difference between MTA mixed with
      8% and 10% nano-SiO2 in setting time, compressive strength, and flexural strength
      (P > .05). CONCLUSIONS: The addition of 8% and 10% of nano-SiO2 to MTA
      accelerated the hydration process, reduced the setting time, and had no adverse
      effect on the compressive and flexural strength of MTA.

PMID- 24139273
TI  - Mixing with propylene glycol enhances the bond strength of mineral trioxide
      aggregate to dentin.
AB  - INTRODUCTION: Mixing mineral trioxide aggregate (MTA) with different proportions
      of propylene glycol (PG) improves its handling property. The aim of this study
      was to evaluate the effect of PG on MTA-dentin push-out bond strength. METHODS:
      Seventy-five 2-mm-thick midroot sections were prepared from single-rooted human
      extracted teeth. The lumen of each slice was enlarged with Gates-Glidden burs.
      The slices were randomly divided into 3 groups (n = 25). In each group, 0.3 mL of
      the liquid was mixed with 1 g MTA (Angelus, Londrina, Brazil). The liquid
      vehicles used in groups 1-3 were 100% distilled water (DW), 20% PG-80% DW, and
      100% PG, respectively. After incubation, the push-out strength of the samples was
      measured using a universal testing machine. The samples were then cut in halves
      and examined under a stereomicroscope to determine the failure pattern. One-way
      analysis of variance followed by the Tukey post hoc test was used to compare the
      push-out strength among groups. RESULTS: There were statistically significant
      differences between groups (P < .001). The push-out strength in group 1 (DW) was
      significantly lower than groups 2 and 3 (P < .001 and P = .022, respectively).
      However, there was no significant difference between groups 2 (DW-PG) and 3 (PG).
      CONCLUSIONS: Mixing MTA with PG increased its push-out bond strength to dentin.
      In the present study, the most suitable ratio was 80% DW-20% PG.

PMID- 24139274
TI  - Smear layer removal and canal cleanliness using different irrigation systems
      (EndoActivator, EndoVac, and passive ultrasonic irrigation): field emission
      scanning electron microscopic evaluation in an in vitro study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effectiveness of
      different irrigating methods in removing the smear layer at 1, 3, 5, and 8 mm
      from the apex of endodontic canals. METHODS: Sixty-five extracted single-rooted
      human mandibular premolars were decoronated to a standardized length of 16 mm.
      Specimens were shaped to ProTaper F4 (Dentsply Maillefer, Ballaigues,
      Switzerland) and irrigated with 5.25% NaOCl at 37 degrees C. Teeth were divided
      into 5 groups (2 control groups [n = 10] and 3 test groups [n = 15]) according to
      the final irrigant activation/delivering technique (ie, sonic irrigation, passive
      ultrasonic irrigation [PUI], or apical negative pressure). Root canals were then
      split longitudinally and observed by field emission scanning electron microscopy.
      The presence of debris and a smear layer at 1, 3, 5, and 8 mm from the apex was
      evaluated. Scores were analyzed by Kruskal-Wallis and Mann-Whitney U tests.
      RESULTS: The EndoActivator System (Dentsply Tulsa Dental Specialties, Tulsa, OK)
      was significantly more efficient than PUI and the control groups in removing the
      smear layer at 3, 5, and 8 mm from the apex. The EndoVac System (Discus Dental,
      Culver City, CA) removed statistically significantly more smear layer than all
      groups at 1, 3, 5, and 8 mm from the apex. At 5 and 8 mm from the apex, PUI and
      the EndoVac did not differ statistically significantly, but both performed
      statistically better than the control groups. CONCLUSIONS: In our study, none of
      the activation/delivery systems completely removed the smear layer from the
      endodontic dentine walls; nevertheless, the EndoActivator and EndoVac showed the
      best results at 3, 5, and 8 mm (EndoActivator) and 1, 3, 5, and 8 mm (EndoVac)
      from the apex.

PMID- 24139275
TI  - Autotransplantation of immature third molars using a computer-aided rapid
      prototyping model: a report of 4 cases.
AB  - INTRODUCTION: Autotransplantation of immature teeth can be an option for
      premature tooth loss in young patients as an alternative to immediately replacing
      teeth with fixed or implant-supported prostheses. The present case series reports
      4 successful autotransplantation cases using computer-aided rapid prototyping
      (CARP) models with immature third molars. METHODS: The compromised upper and
      lower molars (n = 4) of patients aged 15-21 years old were transplanted with
      third molars using CARP models. Postoperatively, the pulp vitality and the
      development of the roots were examined clinically and radiographically. The
      patient follow-up period was 2-7.5 years after surgery. RESULTS: The long-term
      follow-up showed that all of the transplants were asymptomatic and functional.
      Radiographic examination indicated that the apices developed continuously and the
      root length and thickness increased. The final follow-up examination revealed
      that all of the transplants kept the vitality, and the apices were fully
      developed with normal periodontal ligaments and trabecular bony patterns.
      CONCLUSIONS: Based on long-term follow-up observations, our 4 cases of
      autotransplantation of immature teeth using CARP models resulted in favorable
      prognoses. The CARP model assisted in minimizing the extraoral time and the
      possible Hertwig epithelial root sheath injury of the transplanted tooth.

PMID- 24139276
TI  - Case series: tooth retention 5 years after irretrievable separation of
      LightSpeedLSX instruments.
AB  - INTRODUCTION: Of 3,216 root canals treated endodontically at the Creighton
      University School of Dentistry from September 1, 2005, to August 31, 2007, with
      LightSpeedLSX instruments (LightSpeed Technology, Inc, San Antonio, TX), there
      were 12 cases of irretrievable instrument separation. More than 5 years after the
      separations, an attempt was made to contact the patients and assess for healing
      and tooth retention. METHODS: Third- and fourth-year dental students performed
      root canal procedures according to protocol from September 1, 2005, to August 31,
      2007. A database was collected during the 24-month period recording cases with
      irretrievable LightspeedLSX separation. Efforts were made from July 2011 to
      December 2011 to contact the 12 patients for endodontic follow-up. Clinical and
      radiographic evaluations of healing were performed. RESULTS: Of the 12 patients
      with irretrievable separations, 8 patients were contacted and 5 returned to
      Creighton University School of Dentistry for follow-up. All 8 contacted patients
      confirmed the presence of the root canal-treated tooth in question, and the teeth
      of the 5 evaluated patients were determined to be asymptomatic and functional.
      Radiographic analysis resulted in 2 teeth being classified as complete healing, 2
      as uncertain healing, and 1 as no healing. CONCLUSIONS: The 100% tooth retention
      rate and the lack of symptoms in 8 contacted (5 evaluated) patients 5 years after
      treatment suggests that long-term retention and functionality can occur after
      irretrievable instrument separation. Although tooth retention and functionality
      are desirable outcomes, radiographic findings may be indicative of inadequate
      periapical healing, thus requiring the clinician to evaluate whether additional
      treatment is necessary.

PMID- 24139277
TI  - Does doing housework keep you healthy? The contribution of domestic physical
      activity to meeting current recommendations for health.
AB  - BACKGROUND: Recent lifestyle approaches to physical activity have included the
      promotion of domestic physical activities such as do-it-yourself or home
      maintenance, gardening and housework. Although it is acknowledged that any
      activity is better than none, there is a danger that those undertaking domestic
      'chores' may assume that this activity is moderate intensity and therefore counts
      towards this 150 minute per week target The purpose of this paper was to report
      the contribution domestic physical activity makes to total weekly physical
      activity and the relationship between domestic physical activity and leanness in
      the Northern Ireland population. METHODS: 4563 adults participated in this cross
      sectional survey of physical activity behaviour. Data were collected through face
      to-face interviews using computer assisted personal interviewing. Gender and age
      group differences in domestic MVPA activity and the ratio of domestic to total
      MVPA were explored using non-parametric Kruskal-Wallis tests. Self-reported
      volume and intensity of physical activity (in bouts of 10 minutes or more) in the
      home and self-reported height and weight were used to determine the association
      between domestic physical activity and leanness using an ANCOVA having controlled
      for age, gender, socio-economic and smoking status. RESULTS: 42.7% of the
      population report levels of physical activity which meet or exceed the current
      United Kingdom recommendations. Domestic physical activity accounts for 35.6% of
      the reported moderate to vigorous physical activity (MVPA). For women, if
      domestic physical activity was excluded from total MVPA, only 20.4% would be
      deemed to meet current recommendations. Time spent in domestic physical activity
      at moderate or vigorous intensity was found to be negatively associated with
      leanness (P = 0.024), [R Squared = .132 (Adjusted R Squared = .125)].
      CONCLUSIONS: Domestic physical activity accounts for a significant proportion of
      self-reported daily MVPA particularly among females and older adults however such
      activity is negatively associated with leanness suggesting that this activity may
      not be sufficient to provide all of the benefits normally associated with meeting
      the physical activity guidelines.

PMID- 24139278
TI  - Impact of BMI and BMI change on future drug expenditures in adults: results from
      the MONICA/KORA cohort study.
AB  - BACKGROUND: The evidence on the long-term economic effects of obesity is still
      scarce. This study aims to analyse the impact of body mass index (BMI) and BMI
      change on future pharmaceutical utilisation and expenditures. METHODS: Based on
      data from 2,946 participants in a German population-based health survey
      (MONICA/KORA, 1994/95) and the follow-up study (2004/05), drug intake and
      expenditures were estimated using a bottom-up approach. Using univariate and
      multivariate methods, we analysed the impact of baseline BMI and BMI-change on
      drug utilisation and expenditures after 10 years. RESULTS: The use of
      pharmaceuticals was more likely in moderately and severely obese compared to the
      normal weight group (OR 1.8 and 4.0, respectively). In those who reported
      pharmaceutical intake, expenditures were about 40% higher for the obese groups. A
      1-point BMI-gain in 10 years was, on average, associated with almost 6% higher
      expenditures compared to a constant BMI. CONCLUSION: The results suggest that
      obesity as well as BMI-gain are strong predictors of future drug utilisation and
      associated expenditures in adults, and thus highlight the necessity of timely and
      effective intervention and prevention programmes. This study complements the
      existing literature and provides important information on the relevance of
      obesity as a health problem.

PMID- 24139279
TI  - Heterozygous TREM2 mutations in frontotemporal dementia.
AB  - A causative association was recently demonstrated between homozygous TREM2
      mutations and frontotemporal dementia (FTD)-like syndrome and between
      heterozygous TREM2 exon2 genetic variations and late-onset Alzheimer's disease
      (AD). The objective of this study was to evaluate whether heterozygous TREM2
      genetic variations might be associated to the risk of FTD. TREM2 exon 2 was
      sequenced in a group of 1030 subjects-namely, 352 patients fulfilling clinical
      criteria for FTD, 484 healthy control subjects (HCs), and 194 patients with AD.
      The mutation frequency and the associated clinical characteristics were analyzed.
      We identified 8 missense and nonsense mutations in TREM2 exon 2 in 24 subjects.
      These mutations were more frequent in patients with FTD than in HCs (4.0% vs.
      1.0%, p = 0.005). In particular, TREM2 Q33X, R47H, T66M, and S116C mutations were
      found in FTD and were absent in HCs. These mutations were associated with either
      the semantic variant of primary progressive aphasia or the behavioral variant FTD
      phenotypes. The FTD and AD groups were not significantly different with regard to
      TREM2 genetic variation frequency (AD: 2.6%, p = 0.39). Heterozygous TREM2
      mutations modulate the risk of FTD in addition to increasing susceptibility to
      AD. Additional studies are warranted to investigate the possible role of these
      mutations in the pathogenesis of neurodegenerative disorders.

PMID- 24139280
TI  - SLC1A2 rs3794087 does not associate with essential tremor.
AB  - A recent genome-wide association study of patients with essential tremor (ET)
      from Germany has nominated SLC1A2 rs3794087 as a novel risk factor for disease.
      This association was independently replicated in the Chinese population, albeit
      with an opposite direction of effect. To further define the role of SLC1A2 in ET,
      we genotyped rs3794087 in a North American series consisting of 1347 patients
      with ET and controls. Statistical analysis did not identify significant
      differences in genotype or allele frequencies between healthy controls and
      patients with ET (p > 0.36). These findings therefore do not support a role for
      SLC1A2 rs3794087 in susceptibility to ET in the North American population.
      Further studies in ethnically distinct populations of patients with ET are
      necessary to understand whether genetic variability in SLC1A2 affects disease
      risk for ET. 

PMID- 24139281
TI  - PGRN haploinsufficiency increased Wnt5a signaling in peripheral cells from
      frontotemporal lobar degeneration-progranulin mutation carriers.
AB  - Loss-of-function progranulin (PGRN) mutations have been identified as the major
      cause of frontotemporal lobar degeneration with TDP-43 protein inclusions (FTLD
      TDP). Previously, we reported cell cycle-related alterations in lymphoblasts from
      FTLD-TDP patients, carrying the c.709-1G>A null PGRN mutation, suggesting
      aberrant cell cycle activation in affected neurons. Here we report that PGRN
      haploinsufficiency activates the extracellular signal-regulated protein kinases 1
      and 2 pathway in a Ca(2+), protein kinase C-dependent, and pertussis toxin
      sensitive manner. Addition of exogenous PGRN or conditioned medium from control
      cells normalized the response of PGRN-deficient lymphoblasts to serum activation.
      Our data indicated that noncanonical Wnt5a signaling might be overactivated by
      PGRN deficiency. We detected increased cellular and secreted levels of Wnt5a in
      PGRN-deficient lymphoblasts associated with enhanced phosphorylated calmodulin
      kinase II. Moreover, treatment of control cells with exogenous Wingless-type 5a
      (Wnt5a)-activated Ca(2+)/calmodulin kinase II (CaMKII), increased extracellular
      signal-regulated protein kinases 1 and 2 activity and cell proliferation up to
      the levels found in c.709-1G>A carrier cells. PGRN knockdown SH-SY5Y
      neuroblastoma cells also show enhanced Wnt5a content and signaling. Taken
      together, our results revealed an important role of Wnt signaling in FTLD-TDP
      pathology and suggest a novel target for therapeutic intervention. 

PMID- 24139282
TI  - Spectrum of NOTCH3 mutations in Korean patients with clinically suspicious
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene on
      chromosome 19. Previous studies showed that NOTCH3 contains mutational hotspots
      that can vary among individuals of different ethnic backgrounds. In this study,
      we investigated the spectrum of NOTCH3 mutations in Korean patients with CADASIL.
      We retrospectively analyzed 156 patients who underwent NOTCH3 gene testing for
      molecular diagnosis of CADASIL using Sanger sequencing with a tiered approach.
      First, we screened previously reported mutational hotspots (exons 2-6, 8, 11, 18,
      19, and 22). If no mutation was detected and samples were available, we extended
      our analysis to additional exons (7, 9, 10, 14, 15, 20, 21, 23, and 25). In 45 of
      156 patients (28.8%), 29 mutations and 16 novel variants of unknown significance
      (VUS) were identified. The p.R544C mutation in exon 11 of NOTCH3 was the most
      frequently observed mutation (n = 8), followed by p.R75P in exon 3 (n = 7),
      p.R332C in exon 6 (n = 3), p.R54C in exon 2 (n = 2), and p.R90C in exon 3 (n =
      2). Among the VUS, p.R1175W in exon 22, p.S414C in exon 8, and p.N1207S in exon
      22 were found in 5, 3, and 2 patients, respectively. Other mutations and VUS were
      observed in 1 patient each. Although this was not a prospective, nationwide
      cohort study, the results above suggested that the spectrum of NOTCH3 mutations
      might be different in Koreans than in individuals of Caucasian ethnicity.
      Therefore, further analysis of Koreans with CADASIL might be necessary to
      implement a Korean-specific mutation screening paradigm.

PMID- 24139283
TI  - Green space, social inequalities and neonatal mortality in France.
AB  - BACKGROUND: Few studies have considered using environmental amenities to explain
      social health inequalities.Nevertheless, Green spaces that promote good health
      may have an effect on socioeconomic health inequalities. In developed countries,
      there is considerable evidence that green spaces have a beneficial effect on the
      health of urban populations and recent studies suggest they can have a positive
      effect on pregnancy outcomes. To investigate the relationship between green
      spaces and the spatial distribution of infant mortality taking account
      neighborhood deprivation levels. METHODS: The study took place in Lyon
      metropolitan area, France. All infant deaths that occurred between 2000 and 2009
      were geocoded at census block level. Each census block was assigned greenness and
      socioeconomic deprivation levels. The spatial-scan statistic was used to identify
      high risk cluster of infant mortality according to these neighborhood
      characteristics. RESULTS: The spatial distribution of infant mortality was not
      random with a high risk cluster in the south east of the Lyon metropolitan area
      (p<0.003). This cluster disappeared (p=0.12) after adjustment for greenness level
      and socioeconomic deprivation, suggesting that these factors explain part of the
      spatial distribution of infant mortality. These results are discussed using a
      conceptual framework with 3 hypothetical pathways by which green spaces may have
      a beneficial effect on adverse pregnancy outcomes: (i) a psychological pathway,
      (ii) a physiological disruption process and (iii) an environmental pathway.
      CONCLUSIONS: These results add some evidence to the hypothesis that there is a
      relationship between access to green spaces and pregnancy outcomes but further
      research is required to confirm this.

PMID- 24139284
TI  - DSM-IV diagnosis in depressed primary care patients with previous psychiatric ICD
      10 bipolar disorder.
AB  - BACKGROUND: In the past 20 years, much evidence has accumulated against the
      overly restrictive diagnostic concepts of hypomania in DSM-IV and DSM-IV-TR. We
      tested DSM-IV-TR and a broader modified version (DSM-IV-TRm) for their ability to
      detect bipolarity in patients who had been treated for bipolar disorders (BD) in
      psychiatric settings, and who now consulted general practitioners (GPs) for new
      major depressive episodes (MDE). METHODS: Bipolact II was an observational,
      single-visit survey involving 390 adult patients attending primary care for MDE
      (DSM-IV-TR criteria) in 201 GP offices in France. The participating GPs (53.3 +/-
      6.5 years old, 80.1% male) were trained by the Bipolact Educational Program, and
      were familiar with the medical care of depressive patients. RESULTS: Of the 390
      patients with MDE, 129 (33.1%) were previously known as bipolar patients (ICD-10
      criteria). Most of the latter bipolar patients (89.7%) had previously been
      treated with antidepressants. Only 9.3% of them met DMS-IV-TR criteria for BD.
      Conversely, 79.1% of the 129 bipolar patients met DMS-IV-TRm criteria for BD and
      showed strong associations with impulse control disorders and manic/hypomanic
      switches during antidepressant treatment. LIMITATIONS: Limited training of
      participating GPs, recall bias of patients, and the study not being
      representative for untreated bipolar patients. CONCLUSIONS: Very few ICD-10
      bipolar patients consulting French GPs for MDE met DSM-IV-TR criteria for bipolar
      diagnosis, which suggests that DSM-IV-TR criteria are insufficient and too
      restrictive for the diagnosis of BD. DSM-IV-TRm was more sensitive, but 20% of
      bipolar patients were undetected.

PMID- 24139285
TI  - A mathematical model for optimizing the indications of liver transplantation in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: The criteria for organ sharing has developed a system that
      prioritizes liver transplantation (LT) for patients with hepatocellular carcinoma
      (HCC) who have the highest risk of wait-list mortality. In some countries this
      model allows patients only within the Milan Criteria (MC, defined by the presence
      of a single nodule up to 5 cm, up to three nodules none larger than 3 cm, with no
      evidence of extrahepatic spread or macrovascular invasion) to be evaluated for
      liver transplantation. This police implies that some patients with HCC slightly
      more advanced than those allowed by the current strict selection criteria will be
      excluded, even though LT for these patients might be associated with acceptable
      long-term outcomes. METHODS: We propose a mathematical approach to study the
      consequences of relaxing the MC for patients with HCC that do not comply with the
      current rules for inclusion in the transplantation candidate list. We consider
      overall 5-years survival rates compatible with the ones reported in the
      literature. We calculate the best strategy that would minimize the total
      mortality of the affected population, that is, the total number of people in both
      groups of HCC patients that die after 5 years of the implementation of the
      strategy, either by post-transplantation death or by death due to the basic HCC.
      We illustrate the above analysis with a simulation of a theoretical population of
      1,500 HCC patients with tumor size exponentially. The parameter lambda obtained
      from the literature was equal to 0.3. As the total number of patients in these
      real samples was 327 patients, this implied in an average size of 3.3 cm and a
      95% confidence interval of [2.9; 3.7]. The total number of available livers to be
      grafted was assumed to be 500. RESULTS: With 1500 patients in the waiting list
      and 500 grafts available we simulated the total number of deaths in both
      transplanted and non-transplanted HCC patients after 5 years as a function of the
      tumor size of transplanted patients. The total number of deaths drops down
      monotonically with tumor size, reaching a minimum at size equals to 7 cm,
      increasing from thereafter. With tumor size equals to 10 cm the total mortality
      is equal to the 5 cm threshold of the Milan criteria. CONCLUSION: We concluded
      that it is possible to include patients with tumor size up to 10 cm without
      increasing the total mortality of this population.

PMID- 24139286
TI  - Comparative energetics and kinetics of autotrophic lipid and starch metabolism in
      chlorophytic microalgae: implications for biomass and biofuel production.
AB  - Due to the growing need to provide alternatives to fossil fuels as efficiently,
      economically, and sustainably as possible there has been growing interest in
      improved biofuel production systems. Biofuels produced from microalgae are a
      particularly attractive option since microalgae have production potentials that
      exceed the best terrestrial crops by 2 to 10-fold. In addition, autotrophically
      grown microalgae can capture CO2 from point sources reducing direct atmospheric
      greenhouse gas emissions. The enhanced biomass production potential of algae is
      attributed in part to the fact that every cell is photosynthetic. Regardless,
      overall biological energy capture, conversion, and storage in microalgae are
      inefficient with less than 8% conversion of solar into chemical energy achieved.
      In this review, we examine the thermodynamic and kinetic constraints associated
      with the autotrophic conversion of inorganic carbon into storage carbohydrate and
      oil, the dominant energy storage products in Chlorophytic microalgae. We discuss
      how thermodynamic restrictions including the loss of fixed carbon during acetyl
      CoA synthesis reduce the efficiency of carbon accumulation in lipids. In
      addition, kinetic limitations, such as the coupling of proton to electron
      transfer during plastoquinone reduction and oxidation and the slow rates of CO2
      fixation by Rubisco reduce photosynthetic efficiency. In some cases, these
      kinetic limitations have been overcome by massive increases in the numbers of
      effective catalytic sites, e.g. the high Rubisco levels (mM) in chloroplasts. But
      in other cases, including the slow rate of plastoquinol oxidation, there has been
      no compensatory increase in the abundance of catalytically limiting protein
      complexes. Significantly, we show that the energetic requirements for producing
      oil and starch relative to the recoverable energy stored in these molecules are
      very similar on a per carbon basis. Presently, the overall rates of starch and
      lipid synthesis in microalgae are very poorly characterized. Increased
      understanding of the kinetic constraints of lipid and starch synthesis,
      accumulation and turnover would facilitate the design of improved biomass
      production systems. 

PMID- 24139287
TI  - Effect evaluation of a two-year complex intervention to reduce loneliness in non
      institutionalised elderly Dutch people.
AB  - BACKGROUND: Public health policy calls for intervention programmes to reduce
      loneliness in the ageing population. So far, numerous loneliness interventions
      have been developed, with effectiveness demonstrated for few of these
      interventions. The loneliness intervention described in this manuscript
      distinguishes itself from others by including multiple intervention components
      and targeting individuals and their environment. Intervention components included
      a mass media campaign, information meetings, psychosocial group courses, social
      activities organised by neighbours, and training of intermediaries. The aim of
      this manuscript is to study the effects of this integrated approach on initial
      and long-term outcomes. METHODS: A quasi-experimental pre-test post-test
      intervention study was conducted among non-institutionalised elderly people aged
      65 years and over to evaluate the effectiveness of the intervention by comparing
      the intervention community and the control community. Data on outputs, initial
      and long-term outcomes, and the overall goal were collected by self-administered
      questionnaires. Data of 858 elderly people were available for the analyses. To
      assess the effect linear regression analyses with adjustments for age, gender,
      church attendance, and mental health were used. In addition, the process
      evaluation provided information about the reach of the intervention components.
      RESULTS: After two years, 39% of the elderly people were familiar with the
      intervention programme. The intervention group scored more favourably than the
      control group on three subscales of the initial outcome, motivation (-4.4%, 95%
      CI-8.3--0.7), perceived social support (-8.2%, 95% CI-13.6--2.4), and subjective
      norm (-11.5%, 95% CI-17.4--5.4). However, no overall effects were observed for
      the long-term outcome, social support, and overall goal, loneliness. CONCLUSIONS:
      Two years after its initiation the reach of the intervention programme was
      modest. Though no effect of the complex intervention was found on social support
      and loneliness, more favourable scores on loneliness literacy subscales were
      induced.

PMID- 24139288
TI  - A simple strategy to decrease fatal carotid blowout syndrome after stereotactic
      body reirradiaton for recurrent head and neck cancers.
AB  - BACKGROUND: This study aimed to compare the therapeutic outcomes and fatal
      carotid blow out syndrome (CBOS) incidence rates between two different
      stereotactic body radiotherapy (SBRT) protocols. METHODS: The study included 75
      patients with inoperable locally recurrent head and neck cancer treated with SBRT
      in our department between June 2007 and March 2011. The first 43 patients were
      treated sequentially (group I). Then our SBRT protocol was changed due to the
      high rate of CBOS, and the following 32 patients were treated every other day in
      a prospective institutional protocol (group II). RESULTS: Median overall survival
      in group I and group II was 11 months and 23 months, respectively (P = 0.006). We
      observed 11 cases of CBOS. Only 1 of 7 patients (14%) with CBOS survived in group
      I, whereas 2 of 4 patients (50%) in group II remain alive. CBOS free median
      overall survivals were 9 months, and 23 months in group I and group II
      respectively (P = 0.002). The median radiation dose received by the carotid
      artery in patients with CBOS was 36.5 Gy (range: 34-42.8 Gy), versus 34.7 Gy
      (range: 0-44 Gy) in the patients that didn't have CBOS (P = 0.15). CBOS did not
      occur in any of the patients with a maximum carotid artery radiation dose <34 Gy.
      CONCLUSIONS: Every other day SBRT protocol for re-irradiation of recurrent head
      and neck cancer is promising in terms of decreasing the incidence of fatal CBOS.

PMID- 24139289
TI  - Dosimetric influence of seed spacers and end-weld thickness for permanent
      prostate brachytherapy.
AB  - PURPOSE: The aim of this study was to analyze the dosimetric influence of
      conventional spacers and a cobalt chloride complex contrast (C4) agent, a novel
      marker for MRI that can also serve as a seed spacer, adjacent to (103)Pd, (125)I,
      and (131)Cs sources for permanent prostate brachytherapy. METHODS AND MATERIALS:
      Monte Carlo methods for radiation transport were used to estimate the dosimetric
      influence of brachytherapy end-weld thicknesses and spacers near the three
      sources. Single-source assessments and volumetric conditions simulating prior
      patient treatments were computed. Volume-dose distributions were imported to a
      treatment planning system for dose-volume histogram analyses. RESULTS: Single
      source assessment revealed that brachytherapy spacers primarily attenuated the
      dose distribution along the source long axis. The magnitude of the attenuation at
      1 cm on the long axis ranged from -10% to -5% for conventional spacers and
      approximately -2% for C4 spacers, with the largest attenuation for (103)Pd.
      Spacer perturbation of dose distributions was less than manufacturing tolerances
      for brachytherapy sources as gleaned by an analysis of end-weld thicknesses.
      Volumetric Monte Carlo assessment demonstrated that TG-43 techniques
      overestimated calculated doses by approximately 2%. Specific dose-volume
      histogram metrics for prostate implants were not perturbed by inclusion of
      conventional or C4 spacers in clinical models. CONCLUSIONS: Dosimetric
      perturbations of single-seed dose distributions by brachytherapy spacers exceeded
      10% along the source long axes adjacent to the spacers. However, no dosimetric
      impact on volumetric parameters was noted for brachytherapy spacers adjacent to
      (103)Pd, (125)I, or (131)Cs sources in the context of permanent prostate
      brachytherapy implants.

PMID- 24139290
TI  - Eating breakfast and dinner together as a family: associations with
      sociodemographic characteristics and implications for diet quality and weight
      status.
AB  - BACKGROUND: Research has shown that adolescents who frequently share evening
      meals with their families experience more positive health outcomes, including
      diets of higher nutritional quality. However, little is known about families
      eating together at breakfast. OBJECTIVE: This study examined sociodemographic
      differences in family meal frequencies in a population-based adolescent sample.
      In addition, this study examined associations of family breakfast meal frequency
      with dietary quality and weight status. DESIGN: Cross-sectional data from EAT
      2010 (Eating and Activity in Teens) included anthropometric assessments and
      classroom-administered surveys completed in 2009-2010. PARTICIPANTS/SETTING:
      Participants included 2,793 middle and high school students (53.2% girls, mean
      age=14.4 years) from Minneapolis/St Paul, MN, public schools. MAIN OUTCOME
      MEASURES: Usual dietary intake was self-reported on a food frequency
      questionnaire. Height and weight were measured. STATISTICAL ANALYSES PERFORMED:
      Regression models adjusted for sociodemographic characteristics, family dinner
      frequency, family functioning, and family cohesion were used to examine
      associations of family breakfast frequency with dietary quality and weight
      status. RESULTS: On average, adolescents reported having family breakfast meals
      1.5 times (standard deviation=2.1) and family dinner meals 4.1 times (standard
      deviation=2.6) in the past week. There were racial/ethnic differences in family
      breakfast frequency, with the highest frequencies reported by adolescents of
      black, Hispanic, Native American, and mixed race/ethnicity. Family breakfast
      frequency was also positively associated with male sex, younger age, and living
      in a two-parent household. Family breakfast frequency was associated with several
      markers of better diet quality (such as higher intake of fruit, whole grains, and
      fiber) and lower risk for overweight/obesity. For example, adolescents who
      reported seven family breakfasts in the past week consumed an average of 0.37
      additional daily fruit servings compared with adolescents who never had a family
      breakfast meal. CONCLUSIONS: Results suggest that eating breakfast together as a
      family can have benefits for adolescents' dietary intake and weight status.

PMID- 24139291
TI  - Effects of Cryptocaryon irritans infection on the survival, feeding, respiratory
      rate and ionic regulation of the marbled rockfish Sebastiscus marmoratus.
AB  - To clarify the effects of a Cryptocaryon irritans infection on the physiological
      functions of the marbled rockfish Sebastiscus marmoratus, this study utilized C.
      irritans at concentrations of 2500; 5000; 7500; 10,000; 20,000; and 30,000
      theronts/fish to infect marbled rockfish weighing 45 +/- 3 g. The survival rate,
      food intake, respiratory rate, serum ion concentrations and gill Na+/K+-ATPase
      activity were determined. With the increase of the infection concentration and
      the passage of time, the survival rate of the rockfish gradually decreased. The
      groups infected with more than 5000 theronts/fish had stopped feeding within 4
      days. The respiratory rates of the fish in the groups infected with 2500 and 5000
      theronts/fish initially increased and then decreased. In contrast, the
      respiratory rate of the fish in the groups infected with more than 7500
      theronts/fish was elevated to levels significantly higher than the control group
      after 12 h. The Na+/K+-ATPase activity and serum Na+ and Cl- concentrations
      increased with increasing infection concentration. In conclusion, the
      physiological functions of the fish infected with low concentrations of C.
      irritans can be effectively restored, whereas a high concentration infection
      induced severe stress. The declined food intake and accelerated respiratory rate
      could be useful for an early warning system as important indicators.

PMID- 24139292
TI  - Surgery first in orthognathic surgery: what have we learned? A comprehensive
      workflow based on 45 consecutive cases.
AB  - PURPOSE: In some patients, "surgery first" (SF) may represent a reasonable
      approach for the expedited correction of a maxillofacial deformity. Based on the
      prospective evaluation of a large sample, this article provides a specific
      orthodontic and surgical protocol, discusses the benefits and limitations of this
      approach, and updates its indications. MATERIALS AND METHODS: Forty-five patients
      were managed with an SF approach. Selected cases presented symmetrical skeletal
      malocclusions with no need for extractions or surgically assisted rapid palatal
      expansion. Periodontal or temporomandibular joint problems and management by an
      orthodontist without experience in orthognathic surgery were considered exclusion
      criteria. Virtual treatment planning included a 3-dimensional orthodontic setup.
      Standard orthognathic osteotomies were followed by buccal interdental
      corticotomies to amplify the regional acceleratory phenomenon. Miniscrews were
      placed for postoperative skeletal stabilization. Orthodontic treatment began 2
      weeks after surgery. Archwires were changed every 2 to 3 weeks. At 12-month
      follow-up, patient satisfaction and orthodontist satisfaction were evaluated on a
      visual analog scale of 1 to 10. Descriptive statistics were computed for all
      study variables. RESULTS: The studied sample consisted of 27 women and 18 men
      (mean age, 23.5 yr). The main motivation for treatment was the wish to improve
      facial esthetics. Bimaxillary surgery was the most common procedure. Mean
      duration of orthodontic treatment was 37.8 weeks, with an average of 22
      orthodontic appointments. Mean patient and orthodontist satisfaction scores were
      9.4 (range, 8 to 10) and 9.7 (range, 8 to 10), respectively. CONCLUSIONS: The SF
      approach significantly shortens total treatment time and is very favorably valued
      by patients and orthodontists. Nevertheless, careful patient selection, precise
      treatment planning, and fluent bidirectional feedback between the surgeon and the
      orthodontist are mandatory.

PMID- 24139293
TI  - Neoplasms of the hard palate.
AB  - PURPOSE: Although the most common neoplastic lesion of the oral cavity is
      squamous cell carcinoma (SCC), primary neoplastic lesions of the hard palate have
      not been systematically reviewed to date. The aim of this study was to determine
      the histopathologic composition and characteristics of neoplasms of the hard
      palate. MATERIALS AND METHODS: A retrospective analysis of 66 patients with a
      primary neoplasm of the hard palate managed at the authors' institution from 1985
      through 2012 was performed. Demographic features, malignancy rate,
      histopathologic characteristics and distribution, TNM staging results, metastasis
      patterns, and management strategies were investigated. RESULTS: The sample was
      composed of 66 patients (mean age, 45.0 yr; 57.6% men). Neoplasms were benign in
      57.6% of cases and malignant in 42.4%. Epithelial neoplasms and mesenchymal
      neoplasms were encountered in 52 patients (78.8%) and 14 patients (21.2%),
      respectively. Minor salivary gland tumors (MSGTs) were the most common
      histopathologic group (60.6%), followed by benign mesenchymal tumors (15.2%),
      SCCs (12.1%), malignant melanomas (6.1%), lymphomas (3.0%), and sarcomas (3.0%).
      Although 75.0% of malignant epithelial neoplasms were at an advanced stage, there
      were no pN+ SCC or malignant MSGT cases at presentation. CONCLUSION: The most
      common neoplasms of the hard palate were MSGTs. SCCs were relatively rare in this
      series. Although three-fourths of neoplasms were at an advanced stage, neck
      metastasis was not a characteristic of malignant epithelial neoplasms located in
      the hard palate.

PMID- 24139294
TI  - Defining predictable patterns of craniomaxillofacial injury in the elderly:
      analysis of 1,047 patients.
AB  - PURPOSE: Currently, nearly 1 in 5 Americans is at least 60 years of age. Bone
      atrophy, decreased capacity for tissue repair, and chronic disease are known to
      influence fracture patterns and operative algorithms in this age group. This
      study presents craniofacial trauma injury patterns and treatment in an elderly
      population at a major urban trauma center. METHODS: Patient records were
      retrospectively reviewed from February 1998 through December 2010. Patients at
      least 60 years of age who met the inclusion criteria for craniofacial fractures
      identified by International Classification of Diseases, Ninth Revision code
      review and confirmed by author review of available computed tomograms were
      studied. Demographic information, fracture type, concomitant injuries, and
      management were recorded. RESULTS: Of 11,084 patients presenting with facial
      fracture, 1,047 were older than 60 years. The most common mechanism of injury was
      falls (50%), and most patients were men (59%). Commonly fractured areas included
      the nose (n = 452, 43%), maxilla (316, 30%), zygoma (312, 30%), orbital floor
      (280, 27%), and mandible (186, 18%), with 51 patients (5%) having a concomitant
      basilar skull fracture. Inpatient mortality and length of stay were significantly
      increased compared with the nongeriatric population (P < .01), although only 5%
      of all fractures were treated operatively. CONCLUSIONS: Fractures in the elderly
      tend to be minimally displaced midfacial fractures that do not warrant surgical
      intervention. Despite conservative management, the elderly are hospitalized
      longer than their younger counterparts, have increased critical care needs, and
      have higher mortality. These data support national medical preparedness in
      anticipating the craniofacial trauma needs of the aging US population and can be
      used to update treatment algorithms for these patients.

PMID- 24139295
TI  - Cardiovascular collapse and disseminated intravascular coagulation as
      complications of ethanol embolization of arteriovenous malformations in the upper
      lip: case report and literature review.
AB  - Ethanol has been used for embolization of arteriovenous malformations (AVMs) for
      3 decades. Cardiovascular collapse (CVC), although a rare complication, has been
      reported and occurs immediately to a few hours after ethanol embolization. The
      present report describes a case of CVC and disseminated intravascular coagulation
      (DIC) after ethanol embolotherapy in a patient with upper lip AVMs. Although
      resuscitated from asystole, the patient died of DIC 2 days later despite
      intensive care treatment. 

PMID- 24139296
TI  - Contemporary management of vascular malformations.
AB  - PURPOSE: To review the literature on vascular malformations and to clarify their
      diagnosis, clinical presentation, and treatment options. MATERIAL AND METHODS:
      The authors reviewed the current literature on vascular malformations looking for
      more innovative and credited diagnostic criteria and treatment protocols.
      RESULTS: The review is divided in 4 sections (capillary, venous, arteriovenous,
      and lymphatic malformations). In each section, the clinical presentation,
      radiologic features, and treatment options for each kind of vascular malformation
      are described. The experience and results of the authors also are presented.
      CONCLUSIONS: Vascular malformations are a heterogeneous group of diseases. Each
      type of malformation has unique features that make it largely different from the
      others. Only a clear and correct diagnosis can lead to optimal results.

PMID- 24139297
TI  - Congenital muscular torticollis in adult patients: literature review and a case
      report using a harmonic scalpel.
AB  - Congenital torticollis is characterized by shortening and fibrosis of the
      sternocleidomastoid (SCM) muscle detected at birth or shortly after birth. This
      leads to a lateral inclination of the head to the ipsilateral shoulder and chin
      deviation to the opposite side. When diagnosed early, most cases can be
      conservatively managed with excellent results. In neglected adult cases, the
      treatment of this entity is more controversial. A review of the different
      treatment options in neglected adult cases of congenital torticollis is
      presented, and a case successfully treated by SCM bipolar release is reported. A
      35-year-old woman diagnosed with congenital torticollis was referred to the
      authors' department. She had been diagnosed at 32 years of age and had been
      conservatively treated, with no success. Physical examination showed a posterior
      region of the left SCM muscle hard to palpation, with head tilt to the same side
      and chin deviation to the right. Bipolar release of the SCM muscle was performed
      under general anesthesia using the harmonic scalpel. Immobilization with a brace
      was applied during the first 2 weeks and manual stretching was performed after
      removal of the brace. Head tilt and movement limitation were resolved, achieving
      good functional and cosmetic results. Although the best treatment results in
      congenital torticollis are achieved during the first years of childhood, bipolar
      release of the SCM muscle followed by postsurgical physical therapy can be
      effective in neglected adult cases. 

PMID- 24139298
TI  - The value of postoperative visits for third molar removal.
AB  - PURPOSE: The clinical follow-up visit after third molar extraction has been cited
      as time consuming and of little benefit to patients. Although telephone follow-up
      has the potential to add value to the surgical management of third molars, sparse
      information exists on the financial context of this alternative. The purpose of
      this study was to show the change in value of third molar extraction with
      telephone follow-up through 1) measurement of the postoperative complication rate
      and 2) costs of telephone versus clinical follow-up. MATERIALS AND METHODS:
      Bivariate comparisons were computed to assess for differences in follow-up type.
      Cost was calculated from a provider's perspective using micro-costing analysis
      that quantified cost differences between postoperative telephone and clinical
      follow-ups. Each visit type was divided into clinical activities and clinicians
      involved. Cost rates (dollars per minute) were derived for each clinician. Each
      clinical activity time was multiplied by clinician cost rate to derive an
      activity-based cost for each activity. Individual activity-based costs were
      summed to derive the total cost of telephone versus clinical follow-up visit.
      RESULTS: Patients who had a telephone follow-up had a similar postoperative
      complication rate (2.1%) as those who had a clinical follow-up (1.9%; P = .94).
      The total cost estimates were $14.26 for telephone follow-up and $63.33 for
      clinical follow-up. Overall, there was a cost savings of $49.07 per patient, or a
      77.4% decrease in cost, when using telephone follow-up. CONCLUSION: Telephone
      follow-ups added value to the operative management of patients having third molar
      extractions by controlling for postoperative complication rate and decreasing
      cost of care.

PMID- 24139299
TI  - Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD):
      a systematic review of randomized clinical trials.
AB  - BACKGROUND: The treatment of postpartum depression with selective serotonin
      reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well
      tolerated, but no recent systematic reviews have been conducted. METHODS: A
      qualitative systematic review of randomized clinical trials on women with
      postpartum depression comparing SSRIs to placebo and/or other treatments was
      performed. A comprehensive literature search of online databases, the
      bibliographies of published articles and grey literature were conducted. Data on
      efficacy, acceptability and tolerability were extracted and the quality of the
      trials was assessed. RESULTS: Six randomised clinical trials, comprising 595
      patients, met quality criteria for inclusion in the analysis. Cognitive
      behavioural intervention, psychosocial community-based intervention,
      psychodynamic therapy, cognitive behavioural therapy, a second-generation
      tricyclic antidepressant and placebo were used as comparisons. All studies
      demonstrated higher response and remission rates among those treated with SSRIs
      and greater mean changes on depression scales, although findings were not always
      statistically significant. Dropout rates were high in three of the trials but
      similar among treatment and comparison groups. In general, SSRIs were well
      tolerated and trial quality was good. LIMITATIONS: There are few trials, patients
      included in the trials were not representative of all patients with postpartum
      depression, dropout rates in three trials were high, and long-term efficacy and
      tolerability were assessed in only two trials. CONCLUSIONS: SSRIs appear to be
      efficacious and well tolerated in the treatment of postpartum depression, but the
      available evidence fails to demonstrate a clear superiority over other
      treatments.

PMID- 24139300
TI  - Surface and quasi-longitudinal acoustic waves in KTiOAsO4 single crystals.
AB  - Surface and quasi-longitudinal acoustic wave properties have been investigated in
      potassium titanyl arsenate (KTiOAsO4, KTA) single crystals for the first time.
      Surface acoustic wave (SAW) velocity, electromechanical coupling coefficient and
      power flow angle characteristics have been obtained in rotated Y-cut of KTA
      crystals. High SAW electromechanical coupling coefficient (0.4%) is found in Z
      cut of KTA crystals. For high-frequency devices it is promising the resonators on
      quasi-longitudinal acoustic wave in X-cut of KTA crystals with sharp response in
      interdigital transducer conductance at resonance frequency.

PMID- 24139301
TI  - Application of a micro-Brillouin scattering technique to characterize bone in the
      GHz range.
AB  - The evaluation of elastic properties of bone matrix has been investigated using
      several techniques such as nanoindentation and scanning acoustic microscopy
      (SAM). These techniques make use of good spatial resolution, which can prevent
      effects due to microstructures at the level of several hundreds of microns. In
      this paper, micro-Brillouin scattering (MU-BR) is introduced as another possible
      technique to characterize the elastic properties of bone. This technique is well
      known as a non-contact and non-destructive method to evaluate viscoelastic
      properties of transparent materials in the GHz range. Using thin, translucent
      bone specimens with thicknesses of around 100 MUm, and the reflection induced
      optical geometry, ultrasonic wave velocities in the GHz range were obtained.
      Because this technique optically measures thermal phonons in the specimen, we can
      easily measure in-plane anisotropy of wave velocities by rotating the specimen.
      In a single trabecula, the site matched data between SAM and MU-BR showed good
      correlation, revealing the applicability of this technique to characterize
      material properties of bone. Some recent results on the anisotropy in a trabecula
      and the elasticity evaluation of newly and matured bones are also introduced.

PMID- 24139302
TI  - Shear Bloch waves and coupled phonon-polariton in periodic piezoelectric
      waveguides.
AB  - Coupled electro-elastic SH waves propagating in a periodic piezoelectric finite
      width waveguide are considered in the framework of the full system of Maxwell's
      electrodynamic equations. We investigate Bloch-Floquet waves under homogeneous or
      alternating boundary conditions for the elastic and electromagnetic fields along
      the guide walls. Zero frequency stop bands, trapped modes as well as some
      anomalous features due to piezoelectricity are identified. For mixed boundary
      conditions, by modulating the ratio of the length of the unit cell to the width
      of the waveguide, the minimum widths of the stop bands can be moved to the middle
      of the Brillouin zone. The dispersion equation has been investigated also for
      phonon-polariton band gaps. It is shown that for waveguides at acoustic
      frequencies, acousto-optic coupling gives rise to polariton behavior at
      wavelengths much larger than the length of the unit cell but at optical
      frequencies polariton resonance occurs at wavelengths comparable with the period
      of the waveguide. 

PMID- 24139303
TI  - Activation machinery of the small GTPase Arf6.
AB  - The small GTPase ADP-ribosylation factor 6 (Arf6) plays pivotal roles in a wide
      variety of cellular events, including exocytosis, endocytosis, actin cytoskeleton
      reorganization and phosphoinositide metabolism, in various types of cells. To
      control such a wide variety of actions of Arf6, activation of Arf6 could be
      precisely controlled by its activators, guanine nucleotide exchange factors
      (GEFs), in spatial and temporal manners. In this manuscript, we summarize and
      discuss the characteristics of previously identified GEFs specific to Arf6 and
      activation machineries of Arf6. 

PMID- 24139304
TI  - No evidence so far for the dissemination of carbapenemase-producing
      Enterobactericeae in the community in Switzerland.
AB  - BACKGROUND: Carbapenemase-producing Enterobacteriaceae represent an increasing
      threat to public health and to the treatment of serious nosocomial infections.
      The aim of this study was to screen for the presence of carbapenemase-producing
      Enterobacteriaceae in human carriers in community settings in Switzerland, a
      country representative of central Europe. FINDINGS: Three hundred and fourteen
      stool samples of healthy staff members of a meat-processing company and 291 fecal
      swabs from primary care patients were recovered in Switzerland between April 2012
      and July 2012 and were tested for carbapenemase-producing Enterobacteriaceae
      isolates by selecting for growth on a carbapenem-containing selective medium. Six
      resulting isolates (5 Escherichia coli and 1 Citrobacter youngae) were subjected
      to antimicrobial susceptibility tests and PCR analysis by screening for the
      carbapenemase genes bla OXA-48, bla VIM, bla NDM-1, and bla KPC as well as for
      the extended-spectrum beta-lactamase genes bla TEM, bla SHV, bla CTX-M and bla
      CMY-2. No carbapenemase genes were detected. Resistance to beta-lactam
      antibiotics was due to carriage of the extended-spectrum beta-lactamase CTX-M-15
      in 4 isolates, to CTX-M-14 in one further isolate and to the plasmidic AmpC-beta
      lactamase CMY-2 in one isolate. CONCLUSIONS: These results show that
      carbapenemase-producing Enterobacteriaceae are as yet not present in the
      community. Continuous surveillance is necessary to anticipate future trends in
      the prevalence and dissemination of carbapenem resistant isolates in the
      population.

PMID- 24139305
TI  - Neural correlation of successful cognitive behaviour therapy for spider phobia: a
      magnetoencephalography study.
AB  - Cognitive behavioural therapy (CBT) can be an effective treatment for spider
      phobia, but the underlying neural correlates of therapeutic change are yet to be
      specified. The present study used magnetoencephalography (MEG) to study responses
      within the first half second, to phobogenic stimuli in a group of individuals
      with spider phobia prior to treatment (n=12) and then in nine of them following
      successful CBT (where they could touch and manage live large common house
      spiders) at least 9 months later. We also compared responses to a group of age
      matched healthy control participants (n=11). Participants viewed static
      photographs of real spiders, other fear-inducing images (e.g. snakes, sharks) and
      neutral stimuli (e.g. kittens). Beamforming methods were used to localise sources
      of significant power changes in response to stimuli. Prior to treatment,
      participants with spider phobia showed a significant maximum response in the
      right frontal pole when viewing images of real spiders specifically. No
      significant frontal response was observed for either control participants or
      participants with spider phobia post-treatment. In addition, participants'
      subjective ratings of spider stimuli significantly predicted peak responses in
      right frontal regions. The implications for understanding brain-based effects of
      cognitive therapies are discussed. 

PMID- 24139307
TI  - Measurement and control systems for an imaging electromagnetic flow metre.
AB  - Electromagnetic flow metres based on the principles of Faraday's laws of
      induction have been used successfully in many industries. The conventional
      electromagnetic flow metre can measure the mean liquid velocity in axisymmetric
      single phase flows. However, in order to achieve velocity profile measurements in
      single phase flows with non-uniform velocity profiles, a novel imaging
      electromagnetic flow metre (IEF) has been developed which is described in this
      paper. The novel electromagnetic flow metre which is based on the 'weight value'
      theory to reconstruct velocity profiles is interfaced with a 'Microrobotics VM1'
      microcontroller as a stand-alone unit. The work undertaken in the paper
      demonstrates that an imaging electromagnetic flow metre for liquid velocity
      profile measurement is an instrument that is highly suited for control via a
      microcontroller. 

PMID- 24139306
TI  - Discovery and full genome characterization of two highly divergent simian
      immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus
      guereza) in Kibale National Park, Uganda.
AB  - BACKGROUND: African non-human primates (NHPs) are natural hosts for simian
      immunodeficiency viruses (SIV), the zoonotic transmission of which led to the
      emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and
      evolution is limited by incomplete taxonomic and geographic sampling of NHPs,
      particularly in East Africa. In this study, we screened blood specimens from nine
      black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale
      National Park, Uganda, for novel SIVs using a combination of serology and
      "unbiased" deep-sequencing, a method that does not rely on genetic similarity to
      previously characterized viruses. RESULTS: We identified two novel and divergent
      SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering
      the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in
      three and four animals, respectively, but with no animals co-infected.
      Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with
      SIVcol, previously discovered in black-and-white colobus from Cameroon. Although
      SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda,
      SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of
      functional motifs in the extracellular envelope glycoprotein (gp120) revealed
      that SIVkcol-2 is unique among primate lentiviruses in containing only 16
      conserved cysteine residues instead of the usual 18 or more. CONCLUSIONS: Our
      results demonstrate that the genetic diversity of SIVs infecting black-and-white
      colobus across equatorial Africa is greater than previously appreciated and that
      divergent SIVs can co-circulate in the same colobine population. We also show
      that the use of "unbiased" deep sequencing for the detection of SIV has great
      advantages over traditional serological approaches, especially for studies of
      unknown or poorly characterized viruses. Finally, the detection of the first SIV
      containing only 16 conserved cysteines in the extracellular envelope protein
      gp120 further expands the range of functional motifs observed among SIVs and
      highlights the complex evolutionary history of simian retroviruses.

PMID- 24139308
TI  - Solution to automatic generation control problem using firefly algorithm
      optimized I(lambda)D(u) controller.
AB  - Present work focused on automatic generation control (AGC) of a three unequal
      area thermal systems considering reheat turbines and appropriate generation rate
      constraints (GRC). A fractional order (FO) controller named as I(lambda)D(u)
      controller based on crone approximation is proposed for the first time as an
      appropriate technique to solve the multi-area AGC problem in power systems. A
      recently developed metaheuristic algorithm known as firefly algorithm (FA) is
      used for the simultaneous optimization of the gains and other parameters such as
      order of integrator (lambda) and differentiator (MU) of I(lambda)D(u) controller
      and governor speed regulation parameters (R). The dynamic responses corresponding
      to optimized I(lambda)D(u) controller gains, lambda, MU, and R are compared with
      that of classical integer order (IO) controllers such as I, PI and PID
      controllers. Simulation results show that the proposed I(lambda)D(u) controller
      provides more improved dynamic responses and outperforms the IO based classical
      controllers. Further, sensitivity analysis confirms the robustness of the so
      optimized I(lambda)D(u) controller to wide changes in system loading conditions
      and size and position of SLP. Proposed controller is also found to have performed
      well as compared to IO based controllers when SLP takes place simultaneously in
      any two areas or all the areas. Robustness of the proposed I(lambda)D(u)
      controller is also tested against system parameter variations. 

PMID- 24139309
TI  - Can programme theory be used as a 'translational tool' to optimise health service
      delivery in a national early years' initiative in Scotland: a case study.
AB  - BACKGROUND: Theory-based evaluation (TBE) approaches are heralded as supporting
      formative evaluation by facilitating increased use of evaluative findings to
      guide programme improvement. It is essential that learning from programme
      implementation is better used to improve delivery and to inform other
      initiatives, if interventions are to be as effective as they have the potential
      to be. Nonetheless, few studies describe formative feedback methods, or report
      direct instrumental use of findings resulting from TBE. This paper uses the case
      of Scotland's, National Health Service, early years', oral health improvement
      initiative (Childsmile) to describe the use of TBE as a framework for providing
      feedback on delivery to programme staff and to assess its impact on programmatic
      action. METHODS: In-depth, semi-structured interviews and focus groups with key
      stakeholders explored perceived deviations between the Childsmile programme 'as
      delivered' and its Programme Theory (PT). The data was thematically analysed
      using constant comparative methods. Findings were shared with key programme
      stakeholders and discussions around likely impact and necessary actions were
      facilitated by the authors. Documentary review and ongoing observations of
      programme meetings were undertaken to assess the extent to which learning was
      acted upon. RESULTS: On the whole, the activities documented in Childsmile's PT
      were implemented as intended. This paper purposefully focuses on those activities
      where variation in delivery was evident. Differences resulted from the stage of
      roll-out reached and the flexibility given to individual NHS boards to tailor
      local implementation. Some adaptations were thought to have diverged from the
      central features of Childsmile's PT, to the extent that there was a risk to
      achieving outcomes. The methods employed prompted national service improvement
      action, and proposals for local action by individual NHS boards to address this.
      CONCLUSIONS: The TBE approach provided a platform, to direct attention to areas
      of risk within a national health initiative, and to agree which intervention
      components were 'core' to its hypothesised success. The study demonstrates that
      PT can be used as a 'translational tool' to facilitate instrumental use of
      evaluative findings to optimise implementation within a complex health
      improvement programme.

PMID- 24139310
TI  - Accuracy of age estimation methods from orthopantomograph in forensic odontology:
      a comparative study.
AB  - Changes related to chronological age are seen in both hard and soft tissue. A
      number of methods for age estimation have been proposed which can be classified
      in four categories, namely, clinical, radiological, histological and chemical
      analysis. In forensic odontology, age estimation based on tooth development is
      universally accepted method. The panoramic radiographs of 500 healthy Goan,
      Indian children (250 boys and 250 girls) aged between 4 and 22.1 years were
      selected. Modified Demirjian's method (1973/2004), Acharya AB formula (2011), Dr
      Ajit D. Dinkar (1984) regression equation, Foti and coworkers (2003) formula
      (clinical and radiological) were applied for estimation of age. The result of our
      study has shown that Dr Ajit D. Dinkar method is more accurate followed by
      Acharya Indian-specific formula. Furthermore, in this study by applying all these
      methods to one regional population, we have attempted to present dental age
      estimation methodology best suited for the Goan Indian population. 

PMID- 24139311
TI  - Ultrastructural immunolocalization of chatelicidin-like peptides in granulocytes
      of normal and regenerating lizard tissues.
AB  - The presence and localization of cathelicidin anti-microbial peptides in the
      lizard, Anolis carolinensis, were investigated by immunocytochemistry. The study
      showed that immunoreactivity for cathelicidins 1 and 2 was only present in large
      granules of heterophilic-basophilic granulocytes, rarely found in the dermis and
      sub-dermal muscle in normal and more frequently in wound and regenerating skin
      tissues or in the blood. Some immunopositive granulocytes were also observed
      among the keratinocytes of the wound epithelium covering the tail stump and
      occasionally in the regenerating epidermis of the tail. Immunolabeling for
      cathelicidins was also seen in low electrondense amorphous material present on
      the surface of the wound epidermis and on the plasma membrane of bacteria present
      on the surface of corneocytes of the epidermis. Immunolabeling for cathelicidins
      was absent in the other cell types and in control sections. The study suggests
      that cathelicidins are normally stored in granulocytes in the blood or in
      connective tissues, while keratinocytes can be stimulated to produce and possibly
      release these molecules only after injury or microbial invasion. 

PMID- 24139312
TI  - The twelve cranial nerves: a singular exploration.

PMID- 24139313
TI  - [The Spanish Task Force on health promotion and prevention. Too many years of
      insistence unproductive].

PMID- 24139314
TI  - Characterisation of macaque testicular leucocyte populations and T-lymphocyte
      immunity.
AB  - The rodent testis is well established as a site of immune privilege where both
      innate and acquired immune responses are suppressed. Immune cells and responses
      within human or non-human primate testes, by contrast, are poorly characterised.
      This study used multi-colour flow cytometry to characterise the leukocytes in
      testicular cells isolated from 12 young adult pigtail macaques (Macaca
      nemestrina) by collagenase dispersal, and to measure the cytokine responses of
      macaque testicular T-lymphocytes to mitogens. B-lymphocytes and granulocytes were
      present in very low numbers (0.24% and 3.3% of leukocytes respectively),
      indicating minimal blood contamination. A median of 30.8% of the recovered
      testicular leukocytes were CD3+ lymphocytes, with CD4 and CD8 T-lymphocyte
      proportions similar to those in the blood. The proportion of naive T-lymphocytes
      in the testis was low, with significantly higher frequencies of central memory
      cells, compared with the blood. A median of 42.7% of the testicular leukocytes
      were CD163+ macrophages, while 4.5% were CD14+CD163- monocyte-like macrophages.
      Small populations of myeloid and plasmacytoid dendritic cells, NK cells and NKT
      cells were also detected. Following mitogen stimulation, 19.7% of blood T
      lymphocytes produced IFNgamma and/or TNF, whereas significantly fewer (4.4%) of
      the testicular T-lymphocytes responded to stimulation. Our results characterise
      the immune cells within the adult macaque testis and identify a suppression of T
      lymphocyte responses. This study provides a baseline to examine the immunology of
      the primate testis and suggests that testicular immune privilege could also be
      present in primates.

PMID- 24139315
TI  - Hemorrhagic intradiploic epidermoid cyst.

PMID- 24139316
TI  - Estimating the burden of A(H1N1)pdm09 influenza in Finland during two seasons.
AB  - In Finland, the pandemic influenza virus A(H1N1)pdm09 was the dominant influenza
      strain during the pandemic season in 2009/2010 and presented alongside other
      influenza types during the 2010/2011 season. The true number of infected
      individuals is unknown, as surveillance missed a large portion of mild
      infections. We applied Bayesian evidence synthesis, combining available data from
      the national infectious disease registry with an ascertainment model and prior
      information on A(H1N1)pdm09 influenza and the surveillance system, to estimate
      the total incidence and hospitalization rate of A(H1N1)pdm09 infection. The
      estimated numbers of A(H1N1)pdm09 infections in Finland were 211 000 (4% of the
      population) in the 2009/2010 pandemic season and 53 000 (1% of the population)
      during the 2010/2011 season. Altogether, 1.1% of infected individuals were
      hospitalized. Only 1 infection per 25 was ascertained.

PMID- 24139317
TI  - Adaptive evolution of an industrial strain of Saccharomyces cerevisiae for
      combined tolerance to inhibitors and temperature.
AB  - INTRODUCTION: Development of industrial yeast strains with high tolerance towards
      the inhibitors released during biomass pretreatment is critical for bioethanol
      production. Combining this trait with increased thermotolerance would result in a
      more efficient production via Simultaneous Saccharification and Fermentation
      (SSF) as well as reduced cooling costs. The aim of the present work was to
      develop a yeast strain combining these traits. RESULTS: Using a long-term
      adaptation strategy a stable Saccharomyces cerevisiae isolate (ISO12) was evolved
      from the industrial strain Ethanol Red (ER). ISO12, contrary to the parental
      strain, is capable of growing and fermenting the liquid fraction of non
      detoxified spruce hydrolysate at 39 degrees C with an ethanol yield of 0.38 g
      ethanol . g hexoses-1. In contrast with previous studies, the superior phenotype
      of ISO12 does not rely on higher reductase activities for furaldehyde inhibitor
      conversion, but rather on a higher thermotolerance. ISO12 shows a higher capacity
      to ferment hydrolysate at 39 degrees C and higher viability during heat-shock at
      52 degrees C than ER. In the absence of inhibitors, however, both ER and ISO12
      displayed similar growth phenotype at 39 degrees C. CONCLUSIONS: The evolved
      isolate ISO12 shows a superior phenotype than the parental strain ER when both
      stresses, temperature and inhibition by hydrolysate-derived compounds, are
      applied together. The results suggest that the presence of inhibitors depress the
      maximum temperature permissible for growth to a value below 39 degrees C. As a
      result of the adaptation process and acquired improved thermotolerance, ISO12 is
      able to overcome this synergistic effect. Robust strains, such as ISO12, are
      interesting candidates for second generation ethanol production by SSF, as well
      as in tropical countries where fermentations at higher temperature can positively
      impact the production costs.

PMID- 24139318
TI  - Early resident-to-resident physics education in diagnostic radiology.
AB  - The revised ABR board certification process has updated the method by which
      diagnostic radiology residents are evaluated for competency in clinical
      radiologic physics. In this work, the author reports the successful design and
      implementation of a resident-taught physics course consisting of 5 weekly, hour
      long lectures intended for incoming first-year radiology residents in their first
      month of training. To the author's knowledge, this is the first description of a
      course designed to provide a very early framework for ongoing physics education
      throughout residency without increasing the didactic burden on faculty members.
      Twenty-six first-year residents spanning 2 academic years took the course and
      reported subjective improvement in their knowledge (90%) and interest (75%) in
      imaging physics and a high level of satisfaction with the use of senior residents
      as physics educators. Based on the success of this course and the minimal
      resources required for implementation, this work may serve as a blueprint for
      other radiology residency programs seeking to develop revised physics curricula.

PMID- 24139319
TI  - Wicked problems.

PMID- 24139320
TI  - Life is short.

PMID- 24139321
TI  - Consensus-oriented group peer review: a new process to review radiologist work
      output.
AB  - The Joint Commission and other regulatory bodies have mandated that health care
      organizations implement processes for ongoing physician performance review.
      Software solutions, such as RADPEERTM, have been created to meet this need
      efficiently. However, the authors believe that available systems are not
      optimally designed to produce changes in practice and overlook many important
      aspects of quality by excessive focus on diagnosis. The authors present a new
      model of peer review known as consensus-oriented group review, which is based on
      group discussion of cases in a conference setting and places greater emphasis on
      feedback than traditional systems of radiology peer review. By focusing on the
      process of peer review, consensus-oriented group review is intended to optimize
      performance improvement and foster group standards of practice. The authors also
      describe the software tool developed to implement this process of enriched peer
      review. 

PMID- 24139322
TI  - ACR members' response to JACR white paper on the management of incidental
      abdominal CT findings.
AB  - PURPOSE: In October 2010, a white paper was published in this journal that
      represented a consensus of the ACR Incidental Findings Committee, including
      guidance for characterizing, reporting, and managing incidental findings in the
      liver, kidneys, adrenal glands, and pancreas. A survey was conducted of the ACR
      membership to determine how widely this paper had been read, how the information
      is being used, and how management of incidental findings may be improved.
      METHODS: A survey consisting of 14 multiple-choice and 5 free-text responses was
      distributed by e-mail to 14,336 ACR physician members. The survey was open during
      June and July 2012 using SurveyMonkey. Topics included how the paper's
      recommendations had affected practice and the frequency of recommendations for
      additional imaging, how incidental findings are reported, the content and the
      form of the white paper, and the possible effects of tort reform. RESULTS: Of the
      14,336 radiologists contacted, 2,892 (20%) returned the survey; of these, 1,099
      (38%) indicated that they had read the paper. Of the 1,099 radiologists who read
      the paper, 978 (89%) responded that the content was used in clinical practice.
      The white paper led 560 radiologists (51%) to recommend additional imaging less
      often and 33 radiologists (3%) to recommend imaging more often. Tort reform was
      cited by 835 radiologists (76%) as a means to decrease the likelihood of their
      recommending additional imaging. CONCLUSIONS: The 2010 JACR white paper on
      incidental abdominal CT findings has been read by a substantial number of
      radiologists, and among those who read it, the recommendations are being largely
      followed and are leading to a reduction in imaging recommendations. Future
      similar consensus-based white papers could lead to more consistent and effective
      management of incidental imaging findings and likely reduce the overall number of
      patients for whom additional imaging is recommended.

PMID- 24139324
TI  - Intensification of sonochemical degradation of ammonium perfluorooctanoate by
      persulfate oxidant.
AB  - Ammonium perfluorooctanoate (APFO) is an emerging environmental pollutant
      attracting significant attention due to its global distribution, high
      persistence, and bioaccumulation properties. The decomposition of APFO in aqueous
      solution with a combination of persulfate oxidant and ultrasonic irradiation was
      investigated. The effects of operating parameters, such as ultrasonic power,
      persulfate concentration, APFO concentration, and initial media pH on APFO
      degradation were discussed. In the absence of persulfate, 35.5% of initial APFO
      in 46.4 MUmol/L solution under ultrasound irradiation, was decomposed rapidly
      after 120 min with the defluorination ratio reaching 6.73%. In contrast, when 10
      mmol/L persulfate was used, 51.2% of initial APFO (46.4 MUmol/L) was decomposed
      and the defluorination ratio reached 11.15% within 120 min reaction time.
      Enhancement of the decomposition of APFO can be explained by acceleration of
      substrate decarboxylation, induced by sulfate radical anions formed from the
      persulfate during ultrasonic irradiation. The SO4(-*)/APFO reactions at the
      bubble-water interface appear to be the primary pathway for the sonochemical
      degradation of the perfluorinated surfactants.

PMID- 24139323
TI  - Remote population-based intervention for disruptive behavior at age four: study
      protocol for a randomized trial of Internet-assisted parent training (Strongest
      Families Finland-Canada).
AB  - BACKGROUND: Oppositional Defiant Disorder (ODD) is characterized by angry and
      noncompliant behaviour. It is the most common disruptive behaviour disorder
      (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked
      to several long-term difficulties, including disorders of conduct, mood, anxiety,
      impulse-control, and substance abuse. ODD in children is related to parental
      depression, family dysfunction, and impairments in parental work performance.
      Children displaying early DBDs exhibit more symptoms of greater severity, more
      frequent offences, and commit more serious crimes later in life. The goal of the
      Strongest Families Finland Canada (SFFC) Smart Website intervention research
      program is to develop and evaluate an affordable, accessible, effective secondary
      prevention parent training program for disruptive behaviour in preschoolers to
      prevent the negative sequelae of ODD. Strongest Families is an 11-session program
      with two booster sessions that focuses on teaching skills to: strengthen parent
      child relationships; reinforce positive behaviour; reduce conflict; manage daily
      transitions; plan for potentially problematic situations; promote emotional
      regulation and pro-social behaviour and decrease antisocial behaviour.
      METHODS/DESIGN: This protocol paper describes an ongoing population-based
      randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child
      clinics in Turku, Finland and environs to examine the effectiveness of the
      Strongest Families Smart Website intervention compared to an Education Control
      condition. Randomization consists of a 1:1 ratio for intervention versus the
      education group, stratified by the child's sex. The participants randomized to
      the intervention group receive access to the Strongest Families Smart Website and
      weekly telephone coaching sessions. The participants randomized to the Education
      Control condition receive access to a static website with parenting tips.
      Children are followed using parental and daycare teacher measures at 6 and 12
      months after randomization. DISCUSSION: The Strongest Families Smart Website
      intervention is hypothesized to improve parenting skills, reduce child disruptive
      behaviour, reduce parental distress and improve family functioning. These results
      will likely inform subsequent investigations, public policy, and early treatment
      of childhood disruptive behaviour problems. TRIAL REGISTRATION:
      ClinicalTrials.gov # NCT01750996.

PMID- 24139325
TI  - Child-oriented marketing techniques in snack food packages in Guatemala.
AB  - BACKGROUND: Childhood overweight in Guatemala is now becoming a public health
      concern. Child-oriented marketing contributes to increase children's food
      preference, purchase and consumption. This study sought to assess the
      availability of child-oriented snack foods sold in school kiosks and convenience
      stores near public schools in Guatemala, to identify the marketing techniques
      used in child-oriented snack food packages and to classify the snacks as
      "healthy" or "less-healthy". METHODS: We purchased all child-oriented snacks
      found in stores inside and within 200 square meters from four schools in an urban
      community. Snacks were classified as child-oriented if the package had any
      promotional characters, premium offers, children's television/movie tie-ins,
      sports references, or the word "child". We used a checklist to assess child
      oriented references and price. Snacks were classified as "healthy" or "less
      healthy" according to the UK standards for the Nutritional Profiling Model.
      RESULTS: We analyzed 106 packages found in 55 stores. The most commonly used
      technique was promotional characters (92.5%) of which 32.7% were brand-specific
      characters. Premium offers were found in 34% of packages and were mostly
      collectibles (50%). Most marketing techniques were located on the front and
      covered nearly 25% of the package surface. Median (interquartile range) price was
      US$ 0.19 (0.25). Nutrition labels were found in 91 (86%) packages and 41% had a
      nutrition related health claim. Most snacks (97.1%) were classified as "less
      healthy". CONCLUSION: In Guatemala, the food industry targets children through
      several marketing techniques promoting inexpensive and unhealthy snacks in the
      school environment. Evidence-based policies restricting the use of promotional
      characters in unhealthy snack food packages need to be explored as a contributing
      strategy to control the obesity epidemic.

PMID- 24139326
TI  - A mixed methods evaluation of peer support in Bristol, UK: mothers', midwives'
      and peer supporters' views and the effects on breastfeeding.
AB  - BACKGROUND: International studies suggest that breastfeeding interventions in
      primary care are more effective than usual care in increasing short and long term
      breastfeeding rates. Interventions that combine pre- and postnatal components
      have larger effects than either alone, and those that including lay support in a
      multicomponent intervention may be more beneficial. Despite the mixed reports of
      the effectiveness of breastfeeding peer support in the UK, targeted peer support
      services are being established in many areas of the UK. In 2010, NHS Bristol
      Primary Care Trust commissioned a targeted breastfeeding peer support service for
      mothers in 12 lower socio-economic areas of the city, with one antenatal visit
      and postnatal contact for up to 2 weeks. METHODS: Mothers receiving the peer
      support service were invited to complete an on-line survey covering infant
      feeding; breastfeeding support; and confidence in breastfeeding (using the
      Breastfeeding Self-Efficacy Scale). Semi-structured interviews and a focus group
      explored perceptions of mothers, midwives and peer supporters. The effects of the
      service on breastfeeding rates were documented and compared. RESULTS: 163 mothers
      completed the on-line survey; 25 participants were interviewed (14 mothers, 7
      peer supporters and 4 maternity health professionals); exclusive and total
      breastfeeding rates for initiation and at 8 weeks were compared for 12 months
      before and after the service started.The targeted peer support service was
      associated with small non-significant increases in breastfeeding rates,
      (particularly exclusive breastfeeding), compared to the rest of the city. The
      service was very positively evaluated by mothers, health professionals and peer
      supporters. Mothers felt that peer support increased their confidence to
      breastfeed; peer supporters found the contacts rewarding, enjoyable and important
      for mothers; midwives and maternity support workers were positive about the
      continuity of an antenatal visit and postnatal support from the same local
      supporter. CONCLUSIONS: The introduction of a targeted peer support service was
      associated with psycho-social benefits for mothers, health professionals and peer
      supporters. Continuity of peer support with an antenatal visit and postnatal
      support from the same local supporter was also thought to be beneficial.

PMID- 24139327
TI  - Accuracy of deformable image registration for contour propagation in adaptive
      lung radiotherapy.
AB  - BACKGROUND: Deformable image registration (DIR) is an attractive method for
      automatic propagation of regions of interest (ROIs) in adaptive lung
      radiotherapy. This study investigates DIR for automatic contour propagation in
      adaptive Non Small Cell Lung Carcinoma patients. METHODS: Pre and mid-treatment
      fan beam 4D-kVCT scans were taken for 17 NSCLC patients. Gross tumour volumes
      (GTV), nodal-GTVs, lungs, esophagus and spinal cord were delineated on all kVCT
      scans. ROIs were propagated from pre- to mid-treatment images using three DIR
      algorithms. DIR-propagated ROIs were compared with physician-drawn ROIs on the
      mid-treatment scan using the Dice score and the mean slicewise Hausdorff distance
      to agreement (MSHD). A physician scored the DIR-propagated ROIs based on clinical
      utility. RESULTS: Good agreement between the DIR-propagated and physician drawn
      ROIs was observed for the lungs and spinal cord. Agreement was not as good for
      the nodal-GTVs and esophagus, due to poor soft-tissue contrast surrounding these
      structures. 96% of OARs and 85% of target volumes were scored as requiring no or
      minor adjustments. CONCLUSIONS: DIR has been shown to be a clinically useful
      method for automatic contour propagation in adaptive radiotherapy however
      thorough assessment of propagated ROIs by the treating physician is recommended.

PMID- 24139328
TI  - Longitudinal associations between oral health impacts and quality of life among a
      national cohort of Thai adults.
AB  - BACKGROUND: There is limited evidence on the association between oral health and
      general health in middle-income countries. This study analysed data from 60,569
      adult students enrolled at Sukhothai Thammathirat Open University and residing
      throughout Thailand who reported oral health impacts at the 2005 baseline and
      2009 health status based on Short Form (SF-8) survey. FINDINGS: In 2005, 16.4%
      had difficulty chewing and/or swallowing, 13.4% reported difficulty speaking
      and/or discomfort with social interaction, and 10.8% of the cohort reported
      having pain associated with teeth or dentures. Cohort members reporting one or
      more oral health impacts in 2005 had lower SF-8 mean scores in 2009. In
      particular, monotonic dose-response gradients in 2005-2009 associations based on
      multivariate linear regression were found between an increase in number of oral
      impacts (0, 1, 2, 3) and a decline in SF-8 Physical Component Summary scores
      (adjusted means of 50.5, 49.2, 48.6, 47.9) as well as SF-8 Mental Component
      Summary scores (adjusted means of 43.2, 40.9, 40.3, 38.6) in younger cohort
      members. Similar dose response gradients were found in older cohort members.
      CONCLUSIONS: We found strong association between oral health impacts and adverse
      health and quality of life among Thai adults. This finding confirms that oral
      health is one of the key determinants of population health.

PMID- 24139329
TI  - An asthmatic patient with bronchomalacia and good response with continuous
      positive airway pressure.

PMID- 24139330
TI  - Quality spirometry: what do we base our definition on?

PMID- 24139331
TI  - Monophasic synovial sarcoma of the lung.

PMID- 24139332
TI  - A case of interstitial lung disease with apical pleural thickening: idiopathic
      pleuroparenchymal fibroelastosis.

PMID- 24139333
TI  - The importance of diagnosis in interstitial lung disease.

PMID- 24139334
TI  - Median ages at stages of sexual maturity and excess weight in school children.
AB  - BACKGROUND: We aimed to estimate the median ages at specific stages of sexual
      maturity stratified by excess weight in boys and girls. MATERIALS AND METHOD:
      This was a cross-sectional study made in 2007 in Florianopolis, Brazil, with
      2,339 schoolchildren between 8 to 14 years of age (1,107 boys) selected at random
      in two steps (by region and type of school). The schoolchildren were divided
      into: i) those with excess weight and ii) those without excess weight, according
      to the WHO 2007 cut-off points for gender and age. Sexual maturity was self
      evaluated by the subjects according to the Tanner sexual development stages, and
      utilizing median ages for the genitalia, breasts, and pubic hair stages. RESULTS:
      In the boys with excess weight, precocity was observed in the stages 4 for
      genitals and pubic hair and 2 for pubic hair, with the values for excess and
      normal weight. The median ages at the beginning of puberty (stage 2-sexual
      development) for boys and girls in Florianopolis were 10.8 and 10.3 years,
      respectively. CONCLUSION: Excess weight is associated with lower median ages in
      the sexual maturity stages in boys and girls and that it should be taken into
      account when evaluating sexual maturity in children and adolescents.

PMID- 24139335
TI  - [Neurosensory loss hearing of syphilitic etiology in a patient with human
      immunodeficiency virus infection].

PMID- 24139336
TI  - [Application of restriction fragment length polymorphism-polymerase chain
      reaction-flaA and resistotype to identify potential undiagnosed outbreaks of
      campylobacteriosis in Spain].
AB  - INTRODUCTION: Outbreaks of campylobacteriosis are infrequent and usually involve
      a low number of patients, although it is estimated that many more remain
      undiagnosed. The most successful techniques for outbreak investigation in
      Campylobacter spp. (PFGE, MLST) have the drawback of being laborious and not
      available in many laboratories. METHODS: During the year 2008, 352 isolates of C.
      jejuni and C. coli from 16 hospitals were received in our laboratory. All strains
      were genotyped by RFLP-PCR-flaA (flaA type) and phenotyped with their
      resistotype. It was established that the strains of the same species from the
      same hospital, isolated over a period of up to 11 days, with MIC values of+/-1
      dilution with the same flaA type could belong to an outbreak. Strains that met
      these criteria would be later subtyped by KpnI-PFGE and MLST. RESULTS: A total of
      23 out of 352 isolates, distributed in 10 groups, met the criteria for being
      associated with putative undiagnosed outbreaks. The similarity of the PFGE
      profiles in 8 groups was greater than 95% among the isolates from each group. In
      7 of the groups, the sequence types (MLST) were coincident. CONCLUSIONS: The use
      of 2 easy markers (resistotype and RFLP-PCR-flaA) may detect isolates probably
      belonging to an undiagnosed outbreak of campylobacteriosis. Accurate diagnosis
      requires other molecular markers and epidemiological data of each isolate. The
      study suggests that, as in other countries, the number of outbreaks of
      campylobacteriosis in Spain is probably underestimated.

PMID- 24139337
TI  - Legal, ethical, and economic implications of breaking down once-daily fixed-dose
      antiretroviral combinations into their single components for cost reduction.
AB  - The availability of generic lamivudine in the context of the current economic
      crisis has raised a new issue in some European countries: breaking up the once
      daily fixed-dose antiretroviral combinations (FDAC) of
      efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or
      abacavir/lamivudine, in order to administer their components separately, thereby
      allowing the use of generic lamivudine instead of branded emtricitabine or
      lamivudine. The legal, ethical, and economic implications of this potential
      strategy are reviewed, particularly in those patients receiving a once-daily
      single-tablet regimen. An unfamiliar change in antiretroviral treatment from a
      successful patient-friendly FDAC into a more complex regimen including separately
      the components to allow the substitution of one (or some) of them for generic
      surrogates (in the absence of a generic bioequivalent FDAC) could be
      discriminatory because it does not guarantee access to equal excellence in
      healthcare to all citizens. Furthermore, it could violate the principle of non
      maleficence by potentially causing harm both at the individual level (hindering
      adherence and favouring treatment failure and resistance), and at the community
      level (hampering control of disease transmission and transmission of HIV-1
      resistance). Replacing a FDAC with the individual components of that combination
      should only be permitted when the substituting medication has the same
      qualitative and quantitative composition of active ingredients, pharmaceutical
      form, method of administration, dosage and presentation as the medication being
      replaced, and a randomized study has demonstrated its non-inferiority. Finally, a
      strict pharma-economic study supporting this change, comparing the effectiveness
      and the cost of a specific intervention with the best available alternative,
      should be undertaken before its potential implementation. 

PMID- 24139338
TI  - Current-density imaging using ultra-low-field MRI with adiabatic pulses.
AB  - Magnetic resonance imaging (MRI) allows measurement of electric current density
      in an object. The measurement is based on observing how the magnetic field of the
      current density affects the associated spins. However, as high-field MRI is
      sensitive to static magnetic field variations of only the field component along
      the main field direction, object rotations are typically needed to image three
      dimensional current densities. Ultra-low-field (ULF) MRI, on the other hand, with
      B0 on the order of 10-100 MUT, allows novel MRI sequences. We present a rotation
      free method for imaging static magnetic fields and current densities using ULF
      MRI. The method utilizes prepolarization pulses with adiabatic switch-off ramps.
      The technique is designed to reveal complete field and current-density
      information without the need to rotate the object. The method may find
      applications, e.g., in conductivity imaging. We present simulation results
      showing the feasibility of the sequence.

PMID- 24139339
TI  - The house of gastrointestinal medicine: how academic medical centers can build a
      sustainable economic clinical model.
AB  - Academic Medical Centers (AMCs) have been given unique responsibilities to care
      for patients, educate future clinicians, and bring innovative research to the
      bedside. Over the last few decades, this tripartite mission has served the United
      States well, and payers (Federal, State, and commercial) have been willing to
      underwrite these missions with overt and covert financial subsidies. As cost
      containment efforts have escalated, the traditional business model of AMCs has
      been challenged. In this issue, Dr Anil Rustgi and I offer some insights into how
      AMCs must alter their business model to be sustainable in our new world of
      accountable care, cost containment, and clinical integration.

PMID- 24139341
TI  - Spontaneous rectus sheath hematoma: an unusual cause of gross hematuria.
AB  - The diagnosis of a spontaneous rectus sheath hematoma, even in anticoagulated
      patients, requires a high index of suspicion. Gross hematuria is also not
      infrequent in anticoagulated patients. Although urinary symptoms from a rectus
      sheath hematoma have been described, generally it would not be considered a
      common cause of gross hematuria in this population. We report here on 2 cases of
      spontaneous rectus sheath hematoma spontaneously fistulizing into the bladder and
      causing gross hematuria. 

PMID- 24139340
TI  - Neoadjuvant androgen deprivation therapy leads to immediate impairment of
      vitality/hormonal and sexual quality of life: results of a multicenter
      prospective study.
AB  - OBJECTIVE: To evaluate the immediate effects of neoadjuvant androgen deprivation
      therapy (NADT) on health-related quality of life (HRQOL) among patients
      undergoing radiation therapy (RT) for newly diagnosed prostate cancer. METHODS:
      The Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment
      Consortium is a prospective multi-institutional study. HRQOL is measured with the
      Expanded Prostate Cancer Index Composite-26 questionnaire. Differences in patient
      reported HRQOL were observed between pretreatment and 2 months after NADT start
      (and before definitive RT) with significant differences evaluated by paired t
      test. RESULTS: From among 450 patients who completed the Expanded Prostate Cancer
      Index Composite-26 before and 2 months after NADT start, 71 received NADT before
      proceeding with definitive RT. Patients receiving NADT experienced significant
      impairment in vitality/hormonal (P <.0001) and sexual (P <.0001) HRQOL after NADT
      initiation. The mean +/- standard deviation vitality/hormonal score fell from an
      average of 94.1 +/- 9.7 before NADT to 78.7 +/- 16.3 two months after NADT
      initiation; and sexual HRQOL fell from a mean of 51.7 +/- 31.1 pretreatment to
      32.3 +/- 26.1 after NADT initiation. Both these HRQOL domain changes exceeded the
      thresholds for clinical significance. Patients receiving NADT also experienced a
      significant impairment in urinary continence (P = .024), although this difference
      did not meet the criteria for clinical significance. CONCLUSION: In this
      analysis, patients receiving NADT experience significant impairment in sexual and
      vitality/hormonal HRQOL even before starting definitive RT. The significant
      effect of this therapy on HRQOL needs to be considered before initiating NADT in
      men where there is no clear evidence of clinical benefit.

PMID- 24139342
TI  - Reply: To PMID 24063937.

PMID- 24139343
TI  - Editorial comment.

PMID- 24139344
TI  - Unusual presentation of aortic dissection with bilateral testicular pain and
      rapidly deteriorating renal function.

PMID- 24139346
TI  - Visceral fat is correlated with prolonged operative time in laparoendoscopic
      single-site adrenalectomy and laparoscopic adrenalectomy.
AB  - OBJECTIVE: To investigate the effect of visceral fat on operative time and
      discuss whether the measurement of adipose accumulation could be used as a
      sensitive predictor of technical difficulty in performing laparoendoscopic single
      site adrenalectomy (LESS-A) and laparoscopic adrenalectomy (LA). METHODS: We
      reviewed the medical records of 106 patients undergoing LA or LESS-A at our
      institution. Total fat area (TFA) and visceral fat area (VFA) were measured at
      the level of the L4 vertebra by computed tomography. To categorize the type of
      obesity, the VFA/TFA ratio was calculated. Multiple logistic regression analyses
      were performed to identify independent predictors of prolonged operative time.
      RESULTS: The VFA/TFA ratio does not always coincide with body mass index (BMI, r
      = 0.415), and a higher correlation coefficient was observed between operative
      time and the VFA/TFA ratio (r = 0.359) than with that of BMI (r = 0.189).
      Multivariate analysis revealed that pheochromocytoma, tumor size >= 5 cm, and the
      VFA/TFA ratio >= 0.35, defined as the visceral type of adipose accumulation, were
      independent predictive factors for prolonged operative time in LA and LESS-A. We
      were able to stratify patients into short, intermediate, and long operative times
      using these preoperative variables. CONCLUSION: This study revealed that the
      visceral type of adipose accumulation increases operative complexity in LA and
      LESS-A as measured by operative time. The VFA/TFA ratio might be a more sensitive
      indicator of technical difficulty than that of BMI.

PMID- 24139347
TI  - Effects of 5-year treatment with testosterone undecanoate on lower urinary tract
      symptoms in obese men with hypogonadism and metabolic syndrome.
AB  - OBJECTIVE: To investigate the possible effects of testosterone undecanoate (TU)
      injections in a population of obese (mean age 57) hypogonadal men with lower
      urinary tract symptoms (LUTS) in a long-term observational study. METHODS: Twenty
      obese hypogonadal men with metabolic syndrome were treated with TU injections
      every 12 weeks for 60 months; also 20 matched subjects in whom TU was unaccepted
      or contraindicated were used as controls. LUTS severity and the impact of TU
      injections were assessed by differences in International Prostate Symptom Score
      (IPSS), maximum urinary flow (Qmax) rate in milliliters, post-void residual (PVR)
      volume, and prostate size every 12 months in a 5-year controlled study. RESULTS:
      TU injections did not produce differences in IPSS, Qmax, PVR, and prostate size
      in both groups. No modification in prostate-specific antigen (PSA) and hematocrit
      levels was also found between the 2 groups. Interestingly, controls showed
      increased incidence of prostatitis than TU-treated men (10% vs 30%, P <.01).
      CONCLUSION: We showed that 5 years of TU treatment did not change IPSS, PVR,
      Qmax, or prostate size in obese hypogonadal men with metabolic syndrome and
      moderate LUTS at baseline. Therefore, long-term TU replacement therapy is a safe
      and effective treatment for reverting hypogonadal features related to metabolic
      syndrome and does not impact negatively on LUTS and prostate volume.

PMID- 24139348
TI  - The processus vaginalis transection method to prevent postradical prostatectomy
      inguinal hernia: long-term results.
AB  - OBJECTIVE: To evaluate the long-term effect of the processus vaginalis
      transection method, which we previously developed to prevent postradical
      prostatectomy inguinal hernia. METHODS: Our hernia prevention procedure is
      designed to prevent postoperative indirect hernias. The procedure is performed in
      the following order: (1) the spermatic cord is isolated and mobilized in the
      pelvis, (2) the vas deferens is isolated from the spermatic cord and ligated, and
      (3) the processus vaginalis is dissected free of the other spermatic cord
      elements, mainly spermatic vessels, ligated near the peritoneum, and transected.
      Between February 2006 and August 2008, 435 consecutive patients underwent the
      inguinal hernia prevention procedure concurrently with open radical retropubic
      prostatectomy. The control group comprised 433 patients who had undergone radical
      retropubic prostatectomy without hernia prevention immediately before the
      introduction of this hernia prevention procedure was introduced (between January
      2001 and January 2006). RESULTS: No significant complications associated with the
      hernia prevention procedure were observed, except for a few minor peritoneal
      injuries that were easily repaired during surgery. An inguinal hernia developed
      postoperatively in 109 of the 433 control patients (25.2%) during the median
      follow-up of 68 months. In contrast, 4 of the 435 patients (0.9%) who underwent
      the hernia prevention procedure developed an inguinal hernia during the median
      follow-up of 42 months. CONCLUSION: The processus vaginalis transection method is
      safe and effective in the long-term prevention of postradical prostatectomy
      inguinal hernia.

PMID- 24139349
TI  - Editorial comment.

PMID- 24139350
TI  - Did antenatal diagnosis protect against chronic kidney disease in patients with
      posterior urethral valves? A multicenter study.
AB  - OBJECTIVE: To evaluate the prognostic role of antenatal diagnosis of posterior
      urethral valves (PUVs) on ultimate renal function. METHODS: Between 1990 and
      2010, 315 patients with PUVs were diagnosed and treated at 2 separate tertiary
      centers. Primary valve ablation was performed in all patients except 18, who
      underwent initial vesicostomy. Patients were divided into two groups: group 1
      included 144 patients who were diagnosed antenatally, and group 2 included 171
      patients with a postnatal diagnosis. Long-term functional and radiologic outcomes
      were assessed. RESULTS: Follow-up was a median 5.5 years (range, 2-15 years).
      Mean age at ablation was 2.5 years (range, 1 day-15 years). Chronic kidney
      disease developed at the end of follow-up in 96 patients (30%): 27 (19%) in group
      1 and 69 (40%) in group 2 (P <.05). The mean nadir serum creatinine was 0.6 and
      0.8 mg/dL in groups 1 and 2, respectively, and the mean final serum creatinine
      was 0.9 and 1.7 mg/dL, respectively (P <.05). Persistent upper tract dilatation
      was noted in 43% of group 1 patients and in 69% of group 2 patients (P <.05).
      CONCLUSION: The potential for recovering renal function is believed to be
      significant in patients in whom early detection of PUVs and, hence, early
      intervention was performed. Antenatal screening and detection of these patients
      might play a significant role in protecting the upper tract and reducing the
      incidence of chronic kidney disease.

PMID- 24139351
TI  - Validation of the Urgency, Weak stream, Incomplete emptying, and Nocturia (UWIN)
      score compared with the American Urological Association Symptoms Score in
      assessing lower urinary tract symptoms in the clinical setting.
AB  - OBJECTIVE: To validate the Urgency, Weak stream, Incomplete emptying, and
      Nocturia (UWIN) survey for patients with lower urinary tract symptoms (LUTS) by
      comparison with the American Urological Association Symptoms Score (AUA-SS). The
      hypothesis is that the UWIN will perform as well as the AUA-SS in assessing LUTS
      symptoms and quality of life. The AUA-SS is complex for many patients and can be
      misunderstood. The UWIN questionnaire was developed to serve as a simpler and
      shorter version of the AUA-SS, with the intent of improving accuracy and
      minimizing error in assessing LUTS. The UWIN consists of 4 questions scored 0-3
      to give a maximum score of 12. METHODS: We screened 700 patients in the urology
      clinic between 2011 and 2012. We enrolled 593 patients who completed the AUA-SS
      survey and UWIN in the same clinic visit. The AUA-SS and UWIN responses were
      evaluated using Spearman correlation coefficients and Bland-Altman graphs.
      RESULTS: Correlation coefficients were calculated between the corresponding AUA
      SS and UWIN items on 593 matched surveys, demonstrating a strong correlation
      coefficient of 0.81 or greater for each question, which was statistically
      significant (P <.0001). The correlation coefficient between the total scores of
      the AUA and UWIN was 0.89 (P <.01). A second analysis was performed using Bland
      Altman plots between AUA-SS and UWIN including total score, quality of life, and
      categories, which showed a good agreement. CONCLUSION: The UWIN appears to
      provide results comparable to the AUA-SS, while using a simpler format and taking
      less time to complete.

PMID- 24139352
TI  - Long-term morbidity of Martius labial fat pad graft in vaginal reconstruction
      surgery.
AB  - OBJECTIVE: To assess the long-term morbidity of Martius labial fat pad (MLFP)
      interposition in vaginal reconstruction procedures at a tertiary institution.
      MATERIALS AND METHODS: After institutional review board approval, medical records
      of consecutive women in a prospective surgical database requiring MLFP as part of
      their vaginal reconstruction were reviewed for demographics, indications for
      MLFP, complications, and outcomes, with minimum of 6 months follow-up. Three MLFP
      groups were compared as follows: (1) vesicovaginal fistula, (2) bladder outlet
      obstruction, and (3) others. Patients were contacted by mailed survey and/or
      structured telephonic interview with Quality of Life score, validated Female
      Sexual Function Index questionnaire, and a specific question addressing Martius
      harvest site, that is, "pain or numbness in labia". RESULTS: Between 1996 and
      2011, 122 women met inclusion criteria, with 25 excluded for lack of follow-up
      details or death. Mean age was 54 years (range, 19-78), with mean BMI 28 kg/m(2)
      (range, 19-43) and mean follow-up of 85 months (range, 6-202). Indications for
      MLFP included vesicovaginal fistula (20), bladder outlet obstruction (60), and
      others (17) (bladder neck closures, urethral diverticulum, and excision of
      duplicate urethra). No perioperative complications were recorded. Of the 97
      women, 79 (81%) had normal sensation, with 5 (5%) reporting pain and 13 (14%)
      reporting numbness, respectively. Nine (7%) reported distortion of labia majora.
      Of the 29 women reporting sexual activity, only 26 (27%) responded to Female
      Sexual Function Index questionnaires with equivocal sexual function outcomes
      between all 3 surgical groups. CONCLUSION: The MLFP has minimal early and delayed
      morbidity at mean 7 years follow-up.

PMID- 24139353
TI  - Midurethral sling is the dominant procedure for female stress urinary
      incontinence: analysis of case logs from certifying American Urologists.
AB  - OBJECTIVE: To investigate contemporary trends in the use of midurethral sling
      procedures for the surgical correction of female stress urinary incontinence over
      the past decade. METHODS: Annualized case log data for female incontinence
      surgeries from certifying and recertifying urologists were obtained from the
      American Board of Urology. Descriptive analysis of the number and type of cases
      per year was performed. Associations between surgeon characteristics and the use
      of female incontinence procedures were evaluated. RESULTS: A total of 6355
      nonpediatric urologists applied for certification or recertification between 2003
      and 2012. Two-thirds (4185) reported performing any procedures for female
      incontinence. Procedures sharply increased from 4632 in 2003 to 7548 in 2004,
      then remained relatively stable between 2005 and 2012 (range, 8014-10,238 cases).
      Traditional procedures decreased from 17% of female incontinence procedures in
      2003 to 5% in 2004 to <1% since 2010 (P <.0005). Midurethral sling procedures
      have risen sharply from 3210 procedures in 2003 to 7200 in 2012 (P <.0005).
      Endoscopic injection treatments have remained stable. CONCLUSION: Midurethral
      slings have been widely adopted by urologists over the last decade. Increase in
      sling usage coincided with a drastic decline in traditional repairs, implying
      that the newer midurethral slings were replacing these traditional procedures for
      the treatment of female incontinence. In addition, the fact that the use of
      periurethral injections did not change significantly during this time period
      indicates that increased sling usage is responsible for most of the decline in
      traditional repairs.

PMID- 24139355
TI  - Reply: To PMID 24139340.

PMID- 24139354
TI  - Racial differences in longitudinal changes in serum prostate-specific antigen
      levels: the Olmsted County Study and the Flint Men's Health Study.
AB  - OBJECTIVE: To determine the distribution of, and racial differences in, changes
      in prostate-specific antigen (PSA) from a population-based sample of men.
      MATERIALS AND METHODS: Data from 2 prospective cohort studies of a random sample
      of white men, aged 40-79 years in 1990, followed biennially through 2007, and
      African American men, aged 40-79 years in 1996, followed through 2000, were
      examined to assess the longitudinal changes in PSA concentrations. Serum PSA
      levels were determined at each examination for both cohorts and observations
      after a diagnosis of prostate cancer or treatment of benign prostatic hyperplasia
      were censored. The observed and estimated annual percentage of change in the
      serum PSA levels were examined by race. RESULTS: At baseline, the median PSA
      level in the white men did not differ from the median level observed in the
      African American men (white men 0.9 ng/mL; African American men 0.9 ng/mL; P =
      .48). However, African American men had a much more rapid increase in the PSA
      level over time compared with the white men (median annual percent change in PSA
      for white men 3.6%/y, African American men 7.9%/y; P <.001). CONCLUSION: These
      data suggest that African American men have more rapid rates of change in the PSA
      levels over time. If the difference in the rate of changes between African
      American and white men is an early indicator of future prostate cancer diagnosis,
      earlier detection in African American men could help to alleviate the racial
      disparities in prostate cancer diagnosis and mortality.

PMID- 24139356
TI  - Bacterial colonization rate of InterStim and infection outcome with staged
      testing.
AB  - OBJECTIVE: To investigate the bacterial colonization rate of the InterStim
      connector and lead during staged testing and the infectious outcome. METHODS: A
      total of 38 consecutive patients who were scheduled to undergo staged InterStim
      surgery were enrolled in the present prospective study. During the second stage
      procedure, immediately after the connector incision was opened, aerobic and
      anaerobic cultures were obtained by swabbing the connector pocket, the connector,
      and the permanent lead itself with sterile swabs. RESULTS: Of the 38 patients, 9
      (24%) had a positive culture at the connector or lead site after the incision was
      opened during the second stage procedure. Of the 9 patients who had a colonized
      connector or lead, 3 (33%) subsequently developed device infection that required
      explantation. In contrast, only 3% of those who did not have colonization
      developed an infection afterward (P = .038). Longer percutaneous testing period
      was associated with a greater colonization rate. Of the 10 patients who underwent
      >14 days of staged testing, 5 (50%) developed connector and/or lead colonization.
      However, only 4 of the 28 patients (14%) who underwent <= 14 days of testing did
      so (P = .036, relative risk 3.5, 95% confidence interval 1.2-10.5). CONCLUSION:
      The risk of InterStim colonization is significant using the staged, tined lead
      testing approach. Testing for >14 days between the 2 stages was associated with
      greater colonization rates. Patients should be evaluated on an ongoing basis
      during staged testing, with attempts to perform generator implantation once
      efficacy has been unequivocally demonstrated to reduce the risk of colonization.

PMID- 24139357
TI  - Concurrent transperitoneal repair for incidentally detected inguinal hernias
      during robotically assisted radical prostatectomy.
AB  - OBJECTIVE: To report our experience with concurrent intraperitoneal inguinal
      herniorrhaphy using prosthetic mesh during robotically assisted radical
      prostatectomy (RARP) for incidentally discovered inguinal hernias. METHODS: We
      performed a retrospective review of 1118 consecutive RARPs performed by one
      surgeon between July 2005 and July 2011. Cases that included concurrent hernia
      repair were compared with a group of patients matched 1:1 for age, body mass
      index, and year of surgery, who underwent RARP alone (controls). RESULTS: A total
      of 91 patients underwent 113 concurrent inguinal hernia repairs during RARP.
      Twenty-two patients (24%) underwent bilateral repair. Of the 69 patients
      undergoing unilateral repair, 41 (45%) underwent left-sided repair, and 29 (31%)
      underwent right-sided repair. Thirty-five (38%) patients had previous inguinal
      hernia repair. Body mass index of cases and controls were 27.5 +/- 3.4 and 27.8
      +/- 3.1 kg/m(2), respectively. Mean operative time in cases was 185 +/- 28
      minutes vs 168 +/- 31 minutes in controls (P <.001). Estimated blood loss was 170
      +/- 61 mL for cases vs 194 +/- 82 mL for controls (P = .03). No differences were
      observed in length of stay or prevalence of postoperative complications. There
      was 1 hernia recurrence, which necessitated repeat repair 1 year after surgery.
      No mesh infections or other complications related to hernia repairs were
      observed. CONCLUSION: Inguinal hernias are a common intraoperative finding during
      RARP. Concurrent repair appears safe and effective with only a slight increase in
      operative time, and no increase in morbidity.

PMID- 24139358
TI  - Pain management practice patterns for common pediatric urology procedures.
AB  - OBJECTIVE: To characterize practice patterns among members of the Society for
      Pediatric Urology. METHODS: A survey instrument assessing pain management was e
      mailed to all members of the Society for Pediatric Urology. Five hundred fifteen
      invitations were sent, 134 were included, for a 26% response rate. Pain
      management strategies were assessed for 7 case scenarios. Surveys were included
      if the responder answered a minimum of 2 case scenarios. Question Pro survey
      engine was used to process the survey. RESULTS: Local/regional block was the most
      frequent intraoperative anesthesia (54%-90%). Epidural/caudal use varied from 19%
      to 42%. For postop opioids, a dichotomy exists between those without age
      restriction and those who wait until the patient is 6 months old. Sixty three
      percent responded that ketorolac was prescribed only if the patient had normal
      renal function, 20% after confirmation of adequate urine output for bilateral
      procedures, 3% when postoperative creatinine was normal, and 14% did not use
      ketorolac at all. In regards to age limitations, most did not indicate a limit
      (53%), whereas a large number required the child to be older than 6 months (26%).
      Regarding local blocks, most urologists perform the block themselves (61%) for
      simple/complex penile surgery or inguinal surgery. Of this group, only 33%
      actually bill for the administration of the block. After a caudal block, a
      minority (26%) of respondents require the patient to void before discharge for
      ambulatory procedures. CONCLUSION: There is no clear consensus in pain management
      for common pediatric urologic procedures. These disparities should be the aim of
      future studies.

PMID- 24139359
TI  - Editorial comment.

PMID- 24139360
TI  - Improved virus removal by high-basicity polyaluminum coagulants compared to
      commercially available aluminum-based coagulants.
AB  - We investigated the effects of basicity, sulfate content, and aluminum hydrolyte
      species on the ability of polyaluminum chloride (PACl) coagulants to remove F
      specific RNA bacteriophages from river water at a pH range of 6-8. An increase in
      PACl basicity from 1.5 to 2.1 and the absence of sulfate led to a reduction of
      the amount of monomeric aluminum species (i.e., an increase of the total amount
      of polymeric aluminum and colloidal aluminum species) in the PACl, to an increase
      in the colloid charge density of the PACl, or to both and, as a result, to high
      virus removal efficiency. The efficiency of virus removal at around pH 8 observed
      with PACl-2.1c, a nonsulfated high-basicity PACl (basicity 2.1-2.2) with a high
      colloidal aluminum content, was larger than that observed with PACl-2.1b, a
      nonsulfated high-basicity PACl (basicity 2.1-2.2) with a high polymeric aluminum
      content. In contrast, although extremely high basicity PACls (e.g., PACl-2.7ns,
      basicity 2.7) effectively removed turbidity and UV260-absorbing natural organic
      matter and resulted in a very low residual aluminum concentration, the virus
      removal ratio with PACl-2.7ns was smaller than the ratio with PACl-2.1c at around
      pH 8, possibly as a result of a reduction of the colloid charge density of the
      PACl as the basicity was increased from 2.1 to 2.7. Liquid (27)Al NMR analysis
      revealed that PACl-2.1c contained Al30 species, which was not the case for PACl
      2.1b or PACl-2.7ns. This result suggests that Al30 species probably played a
      major role in virus removal during the coagulation process. In summary, PACl
      2.1c, which has high colloidal aluminum content, contains Al30 species, and has a
      high colloid charge density, removed viruses more efficiently (>4 log10 for
      infectious viruses) than the other aluminum-based coagulants-including
      commercially available PACls (basicity 1.5-1.8), alum, and PACl-2.7ns-over the
      entire tested pH (6-8) and coagulant dosage (0.54-5.4 mg-Al/L) ranges.

PMID- 24139361
TI  - An update of dermatologist usage of the Physician Quality Reporting System in
      Colorado for 2011.
AB  - The Physician Quality Reporting System (PQRS) was established in 2006 by the
      Centers for Medicare and Medicaid Services (CMS) as part of an incentive process
      to improve healthcare preventive practices. As of 2011, there were 235 PQRS
      measures but only three specific to skin diseases, specifically melanoma. To
      measure current usage of the PQRS among dermatologists in Colorado, a survey was
      distributed at the 2011 Colorado Dermatological Society Meeting. Of the 120
      physician attendees, 60 responded, yielding a response rate of 50%. Compared with
      responses from a similar 2010 survey, a significantly higher number of physicians
      are using PQRS, as well as E-prescribing and EHR systems. This is likely owing to
      the fact that CMS will require mandatory reporting of these measures in 2015.
      Respondents from the current survey commented that a major hurdle to PQRS
      reporting is the inability to submit data through existing EHR or billing
      systems. Currently, CMS requires PQRS reporting through a designated registry
      such as that provided by the AAD. Some practices have opted to report metrics
      such as tobacco and alcohol screening, since these can be reported through their
      billing systems. The results suggest structural improvements in the PQRS
      reporting system could improve compliance. 

PMID- 24139362
TI  - Elastolytic giant cell granuloma: clinic-pathologic review of twenty cases.
AB  - BACKGROUND: O'Brien described four histopathological patterns of actinic
      granuloma (AG). Since then, only single cases and a few series have been reported
      in the literature, most corresponding to cases of the giant cell type. METHODS:
      We reviewed all the cases diagnosed as AG or elastolytic giant cell granuloma
      (EGCG) in our department from 1988 until 2010. The biopsies were classified into
      the four patterns previously described. RESULTS: Giant cell pattern was found to
      be the most frequent (70% of the cases). In four cases, the biopsies showed more
      than one histopathologic pattern. All the lesions were located on sun-exposed
      areas or were related to chronic heat exposure. Diabetes mellitus was associated
      in 40 % of the cases. CONCLUSIONS: The giant cell pattern of EGCG is the most
      frequent. Some cases may share histopathologic features of more than one variant
      and thus, we consider they may be categorized as mixed patterns. Diabetes
      mellitus is the most common associated disease and should always be ruled out.

PMID- 24139363
TI  - Gefitinib-associated vitiligo: report in a man with parotid squamous cell
      carcinoma and review of drug-induced hypopigmentation.
AB  - Gefitinib is a tyrosine kinase inhibitor that targets and inhibits epidermal
      growth factor receptors. It was initially used to treat non-small cell lung
      cancer but has increasingly been used for other solid tumors such as those in the
      breast, colorectal sites, and head and neck, as in our patient. Vitiligo is an
      autoimmune disorder that results in the destruction of melanocytes and subsequent
      skin depigmentation and hypopigmentation. Previously described mucocutanous side
      effects of gefitinib at 250-500 mg/day include alopecia, asteatotic dermatitis,
      desquamation, hyperpigmentation, papulopustular acneiform eruption, pruritus,
      seborrheic dermatitis, and skin fragility. A 54-year-old man with metastatic
      squamous cell carcinoma to the parotid gland developed vitiligo within 1 month of
      starting gefitinib therapy. We retrospectively reviewed the medical literature
      using PubMed, searching: (1) gefitinib side effects, (2) drugs and (3) vitiligo.
      The patient with gefitinib-induced vitiligo continued to receive treatment with
      the drug during which time areas of skin hypopigmentation persisted and
      progressed. Etiology of drug-induced vitiligo includes alopecia areata therapies,
      anticonvulsants, antimalarials, antineoplastics, anti-Parkinson medications, and
      other miscellaneous drugs. No other individuals have been described with
      gefitinib-induced vitiligo. Albeit rare, gefitinib may be associated with the
      development of vitiligo. 

PMID- 24139364
TI  - A case of infraorbital lichen sclerosus.
AB  - We present a 57-year-old man with erosive lichen sclerosus isolated to the
      infraorbital area. 

PMID- 24139365
TI  - Skin infection caused by Scedosporium apiospermum in immunocompromised patients.
      Report of two cases.
AB  - Scedosporium apiospermum is a filamentous fungus that can cause cutaneous or
      extracutaneous disease. A large number of cases have been published over the last
      decades, mainly in patients immunocompromised as a result of their disease or
      treatment. These kinds of infections can progress rapidly and become
      disseminated, leading to very serious or even fatal complications. We report two
      new cases of skin infection by Scedosporium apiospermum from our hospital. 

PMID- 24139366
TI  - A polymorphic, mucocutaneous eruption in a patient with end-stage renal disease.
AB  - An 81-year-old man is presented who developed cryptococcal infection after
      treatment for Clostridium difficile infection. 

PMID- 24139367
TI  - Schimmelpenning syndrome.
AB  - Schimmelpenning syndrome (SS) includes an organoid nevus that follows the lines
      of Blaschko and defects of brain, eyes, bones, or other systems. We report a case
      of a 3-month old female infant, who presented with several thin plaques, with
      irregular borders, yellowish color, which had a verrucous appearance, following
      the lines of Blaschko, mainly occupying the left side of posterior trunk, the
      left face, the right side of the anterior trunk, and the right upper limb. These
      plaques had been present since birth. In addition, she had a flat salmon to
      yellow nevus on the left parietal and temporal region of the scalp, with a bald
      patch. She was diagnosed after birth with an interauricular communication. The
      skin biopsy from the lesion of the right arm revealed an epidermal nevus that
      occupied the epidermis completely. Routine and other complementary laboratory
      blood tests, including platelet count, thyroid function tests, 25-hydroxy-vitamin
      D, parathyroid hormone, and plasma and urinary levels of calcium and phosphorus
      were negative. Cerebral magnetic resonance and renal ultrasound were normal. The
      diagnosis of SS was established. She is being followed in the clinics of
      Dermatology, Cardiology, Pediatrics, and Pediatric Neurology. We report this case
      to point out the importance of investigating patients with epidermal nevus to
      identify associated conditions. 

PMID- 24139368
TI  - Divided or kissing nevus of the penis.
AB  - The divided or kissing nevus is an unusual congenital melanocytic nevus. By
      definition, these nevi appear on skin that separates during embryological
      development. These lesions have been reported on the eyelids, fingers, and rarely
      the penis. We describe an 18 year old uncircumcised male who presented with an
      asymptomatic darkly pigmented patch on the glans penis. He reported that the
      lesion had appeared recently and was enlarging. Physical examination revealed a
      second symmetric lesion on the adjacent foreskin. Punch biopsy of the lesion on
      the glans penis showed abundant intradermal melanocytes devoid of mitoses and
      atypia, consistent with an intradermal melanocytic nevus. Based on the benign
      histologic nature and clinical exam, the lesion was diagnosed as a divided or
      kissing nevus of the penis. Proposed treatments include excision and grafting as
      well as Nd:YAG laser therapy. However, these patients may be safely monitored
      with regular follow-up skin examinations because there is minimal risk of
      malignant transformation. 

PMID- 24139369
TI  - Adherence to a five day treatment course of topical fluocinonide 0.1% cream in
      atopic dermatitis.
AB  - BACKGROUND: Adherence in the treatment of chronic inflammatory skin diseases such
      as atopic dermatitis is poor. Methods to improve adherence have proven difficult.
      PURPOSE: To determine whether a short course of treatment with a high-potency
      corticosteroid will improve adherence compared to longer treatment studies and if
      improvement in disease and itch continues after treatment. METHODS: 10 patients
      with mild to moderate atopic dermatitis were instructed to apply fluocinonide
      0.1% cream twice daily for 5 days. Adherence was self-reported and electronically
      monitored. Treatment outcomes were assessed in terms of Visual Analog Scale of
      Itch (VAS), Eczema Area and Severity Index (EASI), and Investigator Global
      Assessment (IGA) scores. RESULTS: The median adherence rate was 40% (range of 0
      100). The median percent change in VAS from baseline measures on days 7 and 14
      were 90% (range -13, 100, p=0.02) and 52% (range 0, 100, p=0.004). On days 7 and
      14, 20% and 70% patients achieved an EASI-75 and 40% and 60% an IGA of 0 or 1.
      LIMITATIONS: Small sample size limited subgroup analyses. CONCLUSIONS: Adherence
      rates with short-term treatment were similar to previously reported rates in
      longer term treatment studies. However, even non-adherent patients had
      significant improvement in itch and disease severity.

PMID- 24139370
TI  - Acute generalized exanthematous pustulosis due to dextromethorphan.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a rare, severe, pustular,
      cutaneous reaction. We report a case in which a patient developed AGEP after the
      intake of 3 different antitussive agents containing dextromethorphan as the only
      ingredient in common. 

PMID- 24139371
TI  - Indeterminate cell histiocytosis successfully treated with narrowband UVB.
AB  - We present a 47-year-old man with a sudden eruption of more than 100 reddish
      brown papules, which histologically exhibited a dense dermal proliferation of
      large mononuclear cells with vesicular nuclei and abundant pale cytoplasm.
      Electron microscopy and immunohistochemistry revealed findings consistent with
      indeterminate cell histiocytosis and the patient responded well to treatment with
      narrowband UVB therapy. 

PMID- 24139372
TI  - Vestibular papillomatosis as a normal vulvar anatomical condition.
AB  - At the beginning of the nineteen-eighties, vulvar vestibular papillomatosis (VVP)
      was thought to be a human papilloma virus (HPV) disease. Based upon these
      findings many clinicians have been treating this condition with laser ablation or
      by topical application of podophyllin or trichloroacetic acid. Currently, most
      authors believe that VVP should be considered an anatomical variant of the
      vestibular mucosa and not HPV related. We present a case of VVP in which there
      was no histological or molecular evidence of HPV; unnecessary treatment should be
      avoided. 

PMID- 24139373
TI  - Cutaneous B-cell chronic lymphocytic leukaemia resembling a granulomatous
      rosacea.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a low-grade lymphoproliferative
      disease. Cutaneous involvement of B-CLL is limited and, in most cases, it
      represents non-specific manifestations related to an impaired immune system.
      Leukemic skin infiltrates (leukemia cutis) occur in 4-20% of patients. Herein we
      report the case of a 65-year-old woman with B-CLL presenting with papular,
      nodular, and plaque skin infiltrates affecting the nose, mimicking granulomatous
      rosacea. We discuss several aspects of rare cutaneous manifestations of B-CLL
      involving the face. 

PMID- 24139375
TI  - A metastatic cancer to skin in an otherwise asymptomatic young man: an unusual
      presentation.
AB  - Cutaneous metastasis is a rare complication of visceral malignancies. We present
      a very unusual case of a 33 year-old seemingly healthy man with a sudden and
      rapidly enlarging skin lesion that was diagnosed as a skin metastasis of his
      visceral malignancy. Abdominopelvic CT scan revealed thickening of the anterior
      wall of the urinary bladder and the fundus and body of the stomach. Skin biopsy
      histopathological findings were suggestive of poorly differentiated metastatic
      carcinoma. The origin of the primary carcinoma was bladder adenocarcinoma or/and
      gastric adenocarcinoma, but the tumor was so poorly differentiated that the
      original source of the tumor could not be defined with certainty. 

PMID- 24139376
TI  - Onychomadesis following childhood hand-foot-mouth disease in two pairs of
      siblings- a familial predisposition?
AB  - Onychomadesis is presented in four patients as a result of hand-foot-mouth
      disease. 

PMID- 24139377
TI  - Childhood sarcoidosis: diagnostic issues.
AB  - Childhood sarcoidosis is a rare granulomatous disorder that affects several
      systems including the lungs, skin, eyes, and bones. On histopathology, non
      caseating granuloma is the classic feature. We present a case of late childhood
      sarcoidosis of the skin, lungs, and bones demonstrating granulomas with fibrinoid
      necrosis, making distinction from tuberculosis difficult. 

PMID- 24139378
TI  - Drug Discovery Today: Technologies (2007) volume 4 issues 3/4.

PMID- 24139379
TI  - Finding the way in the jungle of kinase drug targets.
AB  - Kinase inhibitors are developed for the treatment of various diseases. Because
      multiple factors control disease progression and kinases are part of large
      nonlinear networks, it is complicated to predict which kinase is the best to
      target. We substantiate the need for Systems Biology to assist in dealing with
      this complexity. Then, we discuss some of its contributions to kinase drug
      discovery with potential implications for the validation of kinases as drug
      targets and some of its present limitations.

PMID- 24139380
TI  - Predictive value of cellular methods in toxicological evaluation of lead
      candidates: an insight to hepatotoxicity.

PMID- 24139381
TI  - New trends in diagnostic investigations in poisoned patients.

PMID- 24139382
TI  - Determinants of facility delivery after implementation of safer mother programme
      in Nepal: a prospective cohort study.
AB  - BACKGROUND: There are several barriers for pregnant women to deliver in a health
      care facility. This prospective cohort study investigated factors affecting
      facility delivery and reasons for unplanned place of delivery after
      implementation of the safer mother programme in Nepal. METHODS: Baseline
      interviews using a validated questionnaire were conducted on a sample of 700
      pregnant women representative of the Kaski district in central Nepal. Follow-up
      interviews of the cohort were then conducted within 45 days postpartum. Stepwise
      logistic regression analysis was performed to determine factors associated with
      the facility delivery outcome. RESULTS: Of the 644 pregnant women whose delivery
      location had been identified, 547 (85%) gave birth in a health care facility.
      Women were more likely to deliver in a health facility if they were educated
      especially with higher secondary or above qualification (adjusted odds ratio (OR)
      12.39, 95% confidence interval (CI) 5.09 to 30.17), attended 4 or more antenatal
      care visits (OR 2.15, 95% CI 1.25 to 3.69), and lived within 30 minutes to the
      facility (OR 11.61, 95% CI 5.77 to 24.04). For the 97 women who delivered at
      home, 72 (74.2%) were unplanned, mainly due to quick precipitation of labour
      making it impossible to reach a health facility. CONCLUSIONS: It appeared that
      facility delivery occurs more frequent among educated women and those who live
      nearby, even though maternity services are now freely available in Nepal. Because
      of the difficult terrain and transportation problem in rural areas, interventions
      that make maternity service physically accessible during antenatal period are
      needed to increase the utilisation of health facility for child birth.

PMID- 24139383
TI  - Risk factors associated with human papillomavirus infection status in a Korean
      cohort.
AB  - By surveying extensive epidemiological behavioural and sexual risk factors in a
      Korean twin cohort, risk factors for human papillomavirus (HPV) infection were
      investigated in South Korea. A total of 912 vaginal specimens were collected from
      the Healthy Twin Study, consisting of twins and their families. A range of
      epidemiological, behavioural, and sexual activity characteristics were evaluated
      using multivariate logistic regression analyses of family and twin relationships,
      adjusted to elucidate the risk factors for HPV infection. Of the various
      epidemiological characteristics, the possibility of extramarital affairs [odds
      ratio (OR) 2.48, 95% confidence interval (CI) 1.02-6.02] significantly increased
      the prevalence of HPV infection. Our multivariate regression analysis indicated
      that oral contraceptive use (OR 40.64, 95% CI 0.99-1670.7) and history of
      sexually transmitted disease (OR 2.56, 95% CI 0.93-7.10) were strongly associated
      with an increase in HPV infection. On the other hand, more frequent vaginal
      douching (OR 0.32, 95% CI 0.13-0.77) significantly decreased the prevalence of
      HPV infection. Our results suggested that HPV infection is associated with both
      biological and behavioural factors.

PMID- 24139384
TI  - Willingness to pay for a 4% chlorhexidine (7.1% chlorhexidine digluconate)
      product for umbilical cord care in rural Bangladesh: a contingency valuation
      study.
AB  - BACKGROUND: Recent trials in Bangladesh, Nepal, and Pakistan have shown that
      chlorhexidine is an effective antiseptic for umbilical cord care compared to
      existing community-based cord care practices. Because of the aggregate reduction
      in neonatal mortality in these trials, interest is high in introducing a 7.1%
      chlorhexidine digluconate liquid or gel that delivers 4% chlorhexidine for
      umbilical cord care in Bangladesh and elsewhere. METHODS: In 2010, we conducted a
      household survey applying a contingent valuation method with 1717 eligible
      couples (pregnant women or women with a first child younger than 6 months old,
      and their husbands) in the rural subdistricts of Abhoynagar and Mirsarai in
      Bangladesh to assess their willingness to pay for three types of umbilical cord
      care products at different price points. Each respondent was asked about
      willingness to pay prefixed prices for any one of three 7.1% chlorhexidine
      digluconate products: 1) a single-dose liquid, 2) a multi-dose liquid, or 3) a
      gel formulation. Each also reported the maximum price they were independently
      willing to pay for their selected product. We compared participant willingness-to
      pay responses to the prefixed prices with their independently reported maximum
      prices for each type of the product separately. The comparison identified to what
      extent the respondents' positive responses to the prefixed prices matched their
      independently reported maximum prices. RESULTS: This cross matching revealed that
      willingness to pay the prefixed prices was 41% for the single-dose liquid, 33%
      for the multi-dose liquid, and 31% for the gel formulation. Although the majority
      of the respondents were unwilling to pay the prefixed prices, all were willing to
      pay some amount and reported they could borrow money if necessary. Subsequent
      analysis of responses to the multi-dose liquid showed borrowing money would not
      be required if the unit price was Bangladeshi taka 15-25. CONCLUSIONS: A unit
      price of Bangladeshi taka 15-25 (US$0.21-0.35) for multi-dose 7.1% chlorhexidine
      digluconate liquid would be affordable to the primary target population in
      Bangladesh. Although a large market demand could be generated if the product were
      available at this price point, subsidization may be required to achieve optimal
      coverage, especially among poorer families.

PMID- 24139385
TI  - Intravenous thrombolysis with recombinant tissue plasminogen activator in
      vascular warning syndromes.
AB  - INTRODUCTION: Vascular warning syndromes constitute a neurological emergency due
      to their associated high risk of established stroke. At present, there is no
      strong evidence indicating the best treatment for these patients. The aim of this
      paper is to describe the function of intravenous rt-PA thrombolysis in the
      treatment of vascular warning syndromes. MATERIAL AND METHODS: We reviewed our
      hospital records and the literature to find patients with neurologically
      fluctuating profiles and who underwent intravenous rt-PA thrombolysis. RESULTS:
      We retrieved 3 cases from our hospital records and 19 from the literature (15
      males and 7 females). Mean age was 68.7+/-9 years (range: 52-84 years). The mean
      number of episodes before treatment was 4 (range: 2-15 episodes). The maximum
      NIHSS scores ranged from 6 to 22 in different patients. We obtained 24-hour post
      treatment NIHSS scores in 8 cases; of these cases, 6 (75%) had a score of 0, and
      the other 2 (25%) had a score of 12. The Modified Rankin Score calculated at 3
      months of treatment was 0 or 1 in 18 patients (81.8%); these 18 comprised 8 of
      the 10 patients with lacunar warning syndromes (80%), 6 of the 7 with basilar
      warning syndromes (85.7%), and 4 of the 5 with fluctuating non-lacunar, non
      basilar warning syndromes (80%). CONCLUSIONS: Intravenous rt-PA treatment may
      constitute an effective and safe therapeutic alternative for patients with
      neurovascular fluctuations. However, well-designed studies are needed to
      determine the role of intravenous rt-PA thrombolysis in cases of vascular warning
      syndrome.

PMID- 24139386
TI  - Longitudinal evaluation using FP-CIT in patients with parkinsonism.
AB  - OBJECTIVE: To assess a group of patients with parkinsonism using serial studies
      with FP-CIT, basically the initial false negative results. METHODS:
      Restrospective study of 92 patients (55 men and 37 women) who had undergone 2
      different FP-CIT studies because of discrepancies between study results and
      clinical progression. The mean elapsed time between the studies was 26 months
      (SD: 6). We performed a semi-quantitative study using the patient's clinical
      history and the available literature to analyse discrepant cases with a normal
      initial study and subsequent pathological findings. RESULTS: A total of 184
      studies were completed for 92 patients; 11 of those 92 showed discrepancies
      between initial and subsequent studies. Among the 11 discrepant cases, 7 showed a
      normal initial study and pathological findings at a later date. Analysis of the
      predominant clinical features that might explain this behaviour revealed that 4
      of these 7 subjects presented tremor-dominant parkinsonism. Regarding the rest, 1
      presented early stage parkinsonism and was treated with antidopaminergic agents;
      1 was classified as probable multisystem atrophy type C, and the third showed
      clinical signs of atypical parkinsonism without any causes of those signs being
      identified. CONCLUSIONS: Serial FP-CIT studies are unnecessary in the large
      majority of cases, but they may be justifiable in certain clinical situations.

PMID- 24139387
TI  - Oxidative stress in neurological diseases: cause or effect?

PMID- 24139388
TI  - Functional outcome of stroke and the cumulative experience of a stroke unit.
AB  - OBJECTIVE: Patients with acute stroke are more likely to survive and achieve
      independence if they are treated in a stroke unit. Available information in our
      setting is scarce. We analyse the outcomes of our patients on the basis of
      cumulative experience in a stroke unit. PATIENTS AND METHODS: A retrospective
      cohort study of patients admitted to a stroke unit. We differentiate between two
      groups according to the year of admission: group A (July 2007-December 2009) and
      group B (January 2010-December 2011), analysing early outcome based on the score
      on the National Institute of Health stroke scale and mortality at discharge, and
      medium-term outcome in terms of mortality and functional status according to the
      modified Rankin scale at three months. RESULTS: A total 1070 patients were
      included. There were no differences between groups with respect to favourable
      outcome (68.3% vs 63.9), hospital mortality (5.1% vs 6.6%), or 90-day mortality
      (12.8% vs 13.1%). The percentage of patients who were independent at 90 days was
      greater in group B (56.3% vs 65.5%, P=.03). In the multivariate analysis adjusted
      for stroke subtype and fibrinolytic therapy, the association between patient
      independence and admission period remained present. CONCLUSIONS: The probability
      of functional independence in our patients increased alongside accumulated
      experience in our stroke unit with no differences in mortality.

PMID- 24139389
TI  - Ecological assessment of mild cognitive impairment and Alzheimer disease using
      the Rivermead Behavioural Memory Test.
AB  - INTRODUCTION: The Rivermead Behavioural Memory Test (RBMT) is a short,
      ecologically-valid memory test battery that can provide data about a subject's
      memory function in daily life. We used RBMT to examine daily memory function in
      patients with mild cognitive impairment (MCI), Alzheimer disease (AD), and in
      healthy controls. We also evaluated differences between the memory profiles of
      subjects whose MCI remained stable after 1 year and those with conversion to AD.
      PATIENTS AND METHODS: Sample of 91 subjects older than 60 years: 30 controls, 27
      MCI subjects and 34 AD patients. Subjects were assessed using MMSE and RBMT.
      RESULTS: The 40 men and 51 women in the sample had a mean age of 74.29+/-6.71 and
      5.87+/-2.93 years of education. For the total profile and screening RBMT scores
      (P<.001) and total MMSE scores (P<.05), control subjects scored significantly
      higher than those with MCI, who in turn scored higher than AD patients. In all
      subtests, the control group (P<.001) and MCI group (P<.05) were distinguishable
      from the AD group. Prospective, retrospective, and orientation subtests found
      differences between the MCI and control groups (P<.05). MCI subjects who
      progressed to AD scored lower at baseline on the total RBMT and MMSE, and on name
      recall, belongings, story-immediate recall, route-delayed recall, orientation
      (P<.05), face recognition, story-delayed recall, and messages-delayed recall
      sections (P<.01). CONCLUSIONS: RBMT is an ecologically-valid episodic memory test
      that can be used to differentiate between controls, MCI subjects, and AD
      subjects. It can also be used to detect patients with MCI who will experience
      progression to AD.

PMID- 24139390
TI  - [Cryptorchidism: guidelines for surgical management].
AB  - Cryptorchidism is one of the commonest congenital anomalies in the male
      genitalia, affecting 3 to 5% of male full-term neonates. It is a known cause of
      infertility associated with a greater risk of development of germ cell tumor. The
      benefits of early orchidopexy include psychological affects, prevention of
      testicular degeneration and decrease in the risk of testicular cancer.
      Laparoscopy is the best way to diagnose and manage intra-abdominal testes. 

PMID- 24139391
TI  - A critical analysis of sarcoidosis incidence assessment.
AB  - Valid sarcoidosis incidence assessment is contingent on access to medical care,
      thoroughness of reportage, assiduity of radiographic interpretation, employment
      and health care screening policies, misclassification, and population ethnicity.
      To diminish ambiguity and foster inter-population comparison, the term
      "sarcoidosis incidence" must be modified to convey the methodology employed in
      compiling the numerator. In age-delimited cohorts, valid comparison to population
      incidence requires age adjustment due to the age-dependency of incidence. The
      "true incidence" of sarcoidosis is a notional concept: more than 90% of cases are
      subclinical and radiographically inevident. Occupational causal inference based
      on incidence differential vs. populations has been undermined by methodological
      differences in ascertainment and computation. 

PMID- 24139392
TI  - A profile of osteopathic care in private practices in the United Kingdom: a
      national pilot using standardised data collection.
AB  - Increasing interest is being shown in osteopathy on a national and international
      basis. Since little prospective data had been available concerning the day-to-day
      practice of the profession, a standardised data collection tool was developed to
      try and address this issue. The tool development process has been described in an
      earlier paper. The standardised data collection (SDC) tool underwent national
      piloting between April and July 2009 in United Kingdom private practices.
      Osteopaths volunteered to participate and collected data on consecutive new
      patients or patients presenting with a new symptom episode for a period of one
      month; follow-up data were collected for a further two months. A total of 1630
      completed datasets from the SDC pilot were analysed by the project team. Data
      generated from the national pilot showed that lumbar symptoms were the most
      commonly presented in patients (36%), followed by cervical spine (15%),
      sacroiliac/pelvic/groin (7.9%), head/facial area (7%), shoulder (6.8%), and
      thoracic spine (6%). A total of 48.8% of patients reported comorbidities, the
      most common being hypertension (11.7%), followed by asthma (6.6%), and arthritis
      (5.7%). Outcome data were collected looking at the patients' response to
      treatment, and any form of treatment reactions. The profiling information
      collected using the SDC tool provides a contemporary picture of osteopathic
      practice in the United Kingdom. 

PMID- 24139393
TI  - Evaluation of the reactivity of commercially available monoclonal antibodies with
      equine cytokines.
AB  - Research on equine cytokines is often performed by analyses of mRNA. For many
      equine cytokines an analysis on the actual protein level is limited by the
      availability of antibodies against the targeted cytokines. Generation of new
      antibodies is ongoing but time consuming. Thus, testing the reactivity of
      commercially available antibodies for cross-reactivity with equine cytokines is
      of particular interest. Fifteen monoclonal antibodies against IL-1beta, IL-6, IL
      8, IL-12, IL-18 and Granulocyte Macrophage Colony stimulating factor (GM-CSF) of
      different species were evaluated for reactivity with their corresponding equine
      cytokines. Dot Blot (DB) and Western Blot (WB) analyses were performed using
      recombinant equine cytokines as positive controls. Immunohistochemistry (IHC) was
      carried out on equine tissue and flow cytometry on equine PBMC as positive
      controls. As expected, three equine IL-1beta antibodies detected equine IL-1beta
      in DB, WB and IHC. For these, reactivity in IHC has not been described before.
      One of them was also found to be suitable for intracellular staining of equine
      PBMC and flow cytometric analysis. Two antibodies raised against ovine GM-CSF
      cross-reacted with equine GM-CSF in DB, WB and IHC. For these anti-GM-CSF mAbs
      this is the first experimental description of cross-reactivity with equine GM-CSF
      (one mAb was predicted to be cross-reactive in WB in the respective data sheet).
      The other clone additionally proved to be appropriate in flow cytometric
      analysis. Two mAbs targeting porcine IL-18 cross-reacted in IHC, but did not show
      specificity in the other applications. No reactivity was shown for the remaining
      five antibodies in DB, although cross-reactivity of two of the antibodies was
      described previously. The results obtained in this study can provide beneficial
      information for choosing of antibodies for immunological tests on equine
      cytokines. 

PMID- 24139394
TI  - NKp30 enables NK cells to act naturally with fungi.
AB  - NK cells have direct activity against fungal pathogens. Using an unbiased
      systematic approach, Li et al. (2013) find that NKp30 is a major NK cell receptor
      responsible for fungal recognition. Moreover, diminished NKp30 expression is
      associated with reduced antifungal activity in NK cells isolated from HIV
      infected persons. 

PMID- 24139395
TI  - Dynamins are forever: MxB inhibits HIV-1.
AB  - Human MxA (MX1) protein is an interferon-induced restriction factor for a diverse
      range of viruses, whereas the related MxB (MX2) protein was thought to lack such
      activity. Three recent papers, including one in this issue of Cell Host &
      Microbe, show that MxB inhibits human immunodeficiency virus type 1 (HIV-1)
      infection. 

PMID- 24139396
TI  - Is RNA interference a physiologically relevant innate antiviral immune response
      in mammals?
AB  - While RNA interference (RNAi) functions as an antiviral response in plants,
      nematodes, and arthropods, a similar antiviral role in mammals has remained
      controversial. Three recent papers provide evidence that either favors or
      challenges this hypothesis. Here, we discuss these new findings in the context of
      previous research. 

PMID- 24139397
TI  - Lipids in innate antiviral defense.
AB  - It is becoming apparent that infections by a major class of viruses, those with
      envelopes, can be inhibited during their entry at the step of fusion with
      cellular membranes. In this review, we discuss multiple innate immune mechanisms
      that have evolved to modify the lipid composition of cellular and viral membranes
      to inhibit virion fusion of enveloped viruses. 

PMID- 24139398
TI  - The NK receptor NKp30 mediates direct fungal recognition and killing and is
      diminished in NK cells from HIV-infected patients.
AB  - Natural killer (NK) cells are a subset of immune effectors that directly bind and
      kill fungi via a perforin-dependent mechanism. The receptor mediating this
      activity and its potential role in disease remain unknown. Using an unbiased
      approach, we determined that NKp30 is responsible for recognition and killing of
      the fungal pathogens Cryptococcus and Candida. NKp30 was required for NK cell
      fungal conjugate formation, phosphatidylinositol 3-kinase (PI3K) signaling, and
      perforin release. Because fungal infections are a leading cause of death in AIDS
      patients, we examined NKp30 expression in HIV-infected patients. NK cells from
      these patients had diminished NKp30 expression, defective perforin release, and
      blunted microbicidal activity. Surprisingly, interleukin-12 (IL-12) restored
      NKp30 expression and fungal killing. Thus, the NKp30 receptor plays a critical
      role in NK cell antifungal cytotoxicity, and diminished expression of NKp30 is
      responsible for defective antifungal activity of NK cells from HIV-infected
      patients, which can be corrected with IL-12. 

PMID- 24139399
TI  - HIV-1 Vif adaptation to human APOBEC3H haplotypes.
AB  - Several human APOBEC3 deaminases can inhibit HIV-1 replication in vitro. HIV-1
      Vif counteracts this restriction by targeting APOBEC3 for proteasomal
      degradation. Human APOBEC3H (A3H) is highly polymorphic, with natural variants
      differing considerably in anti-HIV-1 activity in vitro. To examine HIV-1
      adaptation to variation in A3H activity in a natural infection context, we
      determined the A3H haplotypes and Vif sequences from 76 recently infected HIV-1
      patients. We detected A3H-specific Vif changes suggesting viral adaptation. The
      patient-derived Vif sequences were used to engineer viruses that specifically
      differed in their ability to counteract A3H. Replication of these Vif-variant
      viruses in primary T cells naturally expressing active or inactive A3H haplotypes
      showed that endogenously expressed A3H restricts HIV-1 replication. Proviral DNA
      from A3H-restricted viruses showed high levels of G-to-A mutations in an A3H
      specific GA dinucleotide context. Taken together, our data validate A3H expressed
      at endogenous levels as a bona fide HIV-1 restriction factor. 

PMID- 24139400
TI  - Host restriction factor SAMHD1 limits human T cell leukemia virus type 1
      infection of monocytes via STING-mediated apoptosis.
AB  - Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T
      cell leukemia and HTLV-1-associated myelopathies. In addition to T cells, HTLV-1
      infects cells of the myeloid lineage, which play critical roles in the host
      innate response to viral infection. Investigating the monocyte depletion observed
      during HTLV-1 infection, we discovered that primary human monocytes infected with
      HTLV-1 undergo abortive infection accompanied by apoptosis dependent on SAMHD1, a
      host restriction factor that hydrolyzes endogenous dNTPs to below the levels
      required for productive reverse transcription. Reverse transcription
      intermediates (RTI) produced in the presence of SAMHD1 induced IRF3-mediated
      antiviral and apoptotic responses. Viral RTIs complexed with the DNA sensor STING
      to trigger formation of an IRF3-Bax complex leading to apoptosis. This study
      provides a mechanistic explanation for abortive HTLV-1 infection of monocytes and
      reports a link between SAMHD1 restriction, HTLV-1 RTI sensing by STING, and
      initiation of IRF3-Bax driven apoptosis. 

PMID- 24139401
TI  - Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and
      CXCR2 to kill leukocytes and promote infection.
AB  - The Staphylococcus aureus leukotoxin ED (LukED) is a pore-forming toxin required
      for the lethality associated with bacteremia in murine models. LukED targets the
      chemokine receptor CCR5 to kill T lymphocytes, macrophages, and dendritic cells.
      LukED also kills CCR5-deficient cells, like neutrophils, suggesting the existence
      of additional cellular receptors. Here, we identify the chemokine receptors CXCR1
      and CXCR2 as the targets of LukED on neutrophils. The LukE subunit binds
      neutrophils in a specific and saturable manner, and this interaction is inhibited
      by CXCL8, the high-affinity endogenous ligand of CXCR1 and CXCR2. LukED
      recognition of CXCR1 and CXCR2 promotes the killing of monocytes and neutrophils
      in vitro. LukED-mediated targeting of CXCR1 and CXCR2(+) cells contributes to S.
      aureus pathogenesis and facilitates lethality in systemically infected mice.
      Thus, LukED is a versatile toxin that endows S. aureus with the ability to
      simultaneously disarm both innate and adaptive compartments of the host immune
      response. 

PMID- 24139402
TI  - Photoconvertible pathogen labeling reveals nitric oxide control of Leishmania
      major infection in vivo via dampening of parasite metabolism.
AB  - The immune system can control infectious diseases through different modes of
      action, including direct killing or spatial confinement. Addressing how the
      immune system impacts pathogen biology in vivo has remained challenging. We
      expressed a photoconvertible fluorescent protein in pathogens in order to track
      their spatial dissemination in infected tissues. In addition, we developed the
      fluorescence recovery after photoconversion (FRAC) method in order to probe
      pathogen metabolic activity in vivo. Combining these two approaches in the
      context of Leishmania major infection of mice and pharmacologically inhibiting
      iNOS, we found that nitric oxide produced during the immune response to L. major
      reduces the metabolic activity of intracellular parasites without necessarily
      exerting direct killing. We propose that this chronic pressure on pathogen
      proliferation represents a sublethal mode of control required for ultimately
      resolving the infection. The ability to probe pathogen biology in response to
      immune defense mechanisms in vivo should create opportunities for better
      dissecting host-pathogen interactions. 

PMID- 24139403
TI  - Tracking viral genomes in host cells at single-molecule resolution.
AB  - Viral DNA trafficking in cells has large impacts on physiology and disease
      development. Current methods lack the resolution and accuracy to visualize and
      quantify viral DNA trafficking at single-molecule resolution. We developed a
      noninvasive protocol for accurate quantification of viral DNA-genome (vDNA)
      trafficking in single cells. Ethynyl-modified nucleosides were used to
      metabolically label newly synthesized adenovirus, herpes virus, and vaccinia
      virus vDNA, without affecting infectivity. Superresolution microscopy and
      copper(I)-catalyzed azide-alkyne cycloaddition (click) reactions allowed
      visualization of infection at single vDNA resolution within mammalian cells.
      Analysis of adenovirus infection revealed that a large pool of capsid-free vDNA
      accumulated in the cytosol upon virus uncoating, indicating that nuclear import
      of incoming vDNA is a bottleneck. The method described here is applicable for the
      entire replication cycle of DNA viruses and offers opportunities to localize
      cellular and viral effector machineries on newly replicated viral DNA, or innate
      immune sensors on cytoplasmic viral DNA. 

PMID- 24139404
TI  - Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which
      was recently approved by US Food and Drug Administration (FDA). There are several
      randomised clinical trials (RCTs) that have investigated the efficacy and safety
      of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic
      review with a meta-analysis of RCTs was undertaken to determine the efficacy and
      safety of tofacitinib in treating patients with RA. METHODS: Electronic and
      clinical trials register databases were searched for published RCTs of
      tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50%
      improvement in the American College of Rheumatology Scale (ACR20 and ACR50)
      response rates, rates of infection, the number of immunological/haematological
      adverse events (AEs), deranged laboratory results (hepatic, renal, haematological
      tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight
      RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were
      observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus
      placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38
      (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg
      bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The
      ACR50 response rate was also significantly higher for patients receiving
      tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI
      2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had
      significantly lower mean neutrophil counts, higher serum creatinine, higher
      percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of
      normal) versus placebo. There were no significant differences in AEs and
      withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious
      and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks.
      However, haematological, liver function tests and lipoproteins should be
      monitored. Long-term efficacy and pharmacovigilance studies are recommended.

PMID- 24139405
TI  - Dosimetric effect of CT contrast agent in CyberKnife treatment plans.
AB  - BACKGROUND: To investigate the effect of computed tomography (CT) contrast
      enhancement (CE) on the 3D dose distributions of non-coplanar small field beams
      in the CyberKnife (CK) treatment planning system (TPS) for the stereotactic
      ablative radiotherapy (SABR). METHODS: Twenty-two pre-CE CT treatment plans were
      recruited to this retrospective plan study. Their post-CE CT plans were based on
      the pre-CE CT plan data and calculated using the same MU and beam paths in either
      Ray-Tracing or Monte Carlo (MC) algorithms. The differences in the doses of the
      beam path and the reference point between the pre- and post-CE CT plans were
      compared. The minimum, maximum, and mean doses in dose-volume histograms (DVHs)
      of target and organs-at-risk (OARs) were also compared. RESULTS: The dose
      differences between the pre- and post-CE plans in a single beam path were less
      than 1.05% in both calculation algorithms, with respect to the prescription dose.
      At the center of the target volume, it was 1.9% (maximum 6.2%) in Ray-Tracing and
      1.6% (maximum 4.0%) in MC. The CA effect showed on average 1.2% difference in the
      OAR maximum dose (maximum 7.8% in Ray-Tracing and 7.2% in MC). In the lung cases,
      the CT CE resulted in a dose difference of 2.4% (from 1.0% to 6.5%) without the
      calculation algorithm effect (maximum 20.3%). CONCLUSIONS: The CK treatment plan
      using the post-CE CT generally afforded less than 2% dose differences from the
      pre-CE CT plan. However, it could be up to 7.8% depending on the target positions
      in a body and be more than 20% with the calculation algorithms. Thus, the post-CE
      CT in CK treatment plans should be used with careful consideration for the CA
      effect, target position, and calculation algorithm factors.

PMID- 24139406
TI  - International mobility, sexual behaviour and HIV-related characteristics of men
      who have sex with men residing in Belgium.
AB  - BACKGROUND: European men who have sex with men (MSM) continue to be
      disproportionally affected by the human immunodeficiency virus (HIV). Several
      factors are contributing to the rates of new HIV infections among MSM. The aim of
      this study was to investigate the potential role of travel behaviour and sexual
      mobility in the spread of HIV and sexually transmitted infections (STI) among
      European MSM. METHODS: Belgian data from the first pan-European MSM internet
      survey EMIS was used (n=3860) to explore individual and contextual determinants
      of sexual behaviour among MSM, who resided in Belgium at the time of data
      collection and who reported having had sexual contact abroad in the last 12
      months. Descriptive and bivariate analyses were performed. Odds ratios and 95%
      confidence intervals were calculated by means of logistic regression. RESULTS:
      MSM who practiced unprotected anal intercourse UAI during their last sexual
      encounter abroad were less likely to be living in a large city (OR:0.62, 95%
      CI:0.45-0,86, p<0.01) and more likely to be HIV positive (OR:6.20, 95% CI:4.23
      9.06, p<0.001) ), to have tested HIV positive in the last 12 months (OR:3.07, 95%
      CI:1.07-8.80, p<0.05), to have been diagnosed with any STI in the last 12 months
      (OR:2.55; 95% CI:1.77-3.67, p<0.05), to have used party drugs (OR:2.22, 95%
      CI:1.59-3.09, p<0.001), poppers (OR:1.52, 95% CI:1.07-2.14, p<0.001) and erection
      enhancing substances (OR:2.23, 95% CI:1.61-3.09, p<0.001) compared to MSM who did
      not have UAI with their last sexual partner abroad. Men having had UAI in the
      last 12 months were more likely to have done so in a neighbouring country of
      Belgium (OR:1.66, 95% CI:1.21-2.29, p<0.001). Different sexual behavioural
      patterns related to condom use and drug use were identified according to HIV test
      status among travelling men. CONCLUSIONS: The results of this study provide
      evidence for the role of international mobility and sexual behavior while
      travelling, in the spread of HIV and STI among MSM in Europe. Further, the
      findings underline the need for development of European cross-border HIV and STI
      interventions with coherent messages and prevention policies for MSM.

PMID- 24139407
TI  - Loading dose of clopidogrel in combination with other antithrombotic therapy for
      capsular warning syndrome.
AB  - A 66-year-old man had repeated stereotypical transient ischemic attacks (TIAs) of
      dysarthria and left hemiparesis. His symptoms were considered capsular warning
      syndrome (CWS), for which the responsible lesion was found on magnetic resonance
      imaging to be in the right putamen expanding to the corona radiata. Although
      administration of antithrombotic therapy including aspirin was ineffective, no
      further TIAs occurred after a loading dose of clopidogrel was added. A loading
      dose of clopidogrel combined with other antithrombotic therapy might be an
      effective treatment for CWS. 

PMID- 24139408
TI  - Brain infarction with a predilection for cerebellum in a patient with double
      outlet left ventricle and vascular malformations.
AB  - Double-outlet left ventricle (DOLV) is a rare congenital heart disease
      characterized by the origin of the great arteries arising predominantly or
      completely from the left ventricle. In this report, we describe a case with brain
      infarction with a predilection for cerebellum in a patient with DOLV and vascular
      malformations. The cerebellar predilection of ischemic lesions appeared to have
      been caused by hemodynamic effects related to the specific anatomy of the
      brachiocephalic trunk. This is further supported by our observation that the mean
      flow velocity was significantly higher in the vertebral arteries than in the
      common carotid arteries. 

PMID- 24139409
TI  - Poor recognition of prompted treatment seeking even with good knowledge of stroke
      warning signs contribute to delayed arrival of acute ischemic stroke patients in
      Thailand.
AB  - Intravenous recombinant tissue plasminogen activator given within 4.5 hours after
      the onset of ischemic stroke is the most powerful standard treatment for patients
      with acute ischemic stroke. However, most of the patients arrive at the hospital
      later than 4.5-hours time window for intravenous thrombolysis. We study the
      factors that might contribute to delayed arrival in patients with acute ischemic
      stroke. One hundred eighty-one acute ischemic stroke patients (or their
      respondents) who admitted in stroke unit of 3 different hospitals were
      interviewed with a questionnaire regarding knowledge of stroke warning signs and
      recognition of prompted treatment seeking (Stroke Act FAST). Eighty-nine patients
      who arrived during 4.5 hours after onset were categorized as on-time group and
      the rest fell into delayed group. Initial National Institutes of Health Stroke
      Scale, nature of onset (sudden or gradual/fluctuation), day interval of the onset
      (8 am to 4 pm, 4 pm to midnight, or midnight to 8 am), mode of transportation,
      place of onset, knowledge of stroke warning signs, and prompted treatment seeking
      (Stroke Act FAST) were compared between 2 groups. Patients in on-time group
      presented with sudden-onset nature much more than patients in delayed group (P =
      .006). Association factors including day interval of the onset, mode of
      transportation, place of onset and knowledge of stroke warning signs are not
      different between groups (P > .05), whereas recognition of prompted treatment
      seeking is better in on-time group than in delayed group. In conclusion, good
      knowledge of stroke warning signs, most severe stroke, onset at workplace, onset
      during daytime, and ambulance for transportation are not associated with early
      arrival within 4.5-hours time window. However, sudden-onset nature and prompted
      treatment seeking may predict early arrival. 

PMID- 24139410
TI  - Associations of serum C-peptide level with body fat distribution and ever stroke
      in nondiabetic subjects.
AB  - BACKGROUND: Although elevated serum C-peptide level as an indicator of insulin
      resistance increases the obesity-associated risk of cardiovascular disease among
      diabetic patients, evidence indicating that serum C-peptide level is associated
      with stroke in nondiabetic subjects is limited. The aim of this study is to
      evaluate the association between serum C-peptide level and ever stroke in
      nondiabetic subjects and investigated the associations of serum C-peptide level
      with body fat distribution and stroke events among nondiabetic subjects. METHODS:
      This study was a population-based cross-sectional study that included 7030
      participants aged 12-85 years. Body fat distribution was determined by dual
      energy X-ray absorptiometry. Serum C-peptide level was measured using the
      radioimmunoassay method. The association between serum C-peptide level and body
      fat distribution was evaluated by multiple linear regression models. Logistic
      regression analysis was performed to calculate the odds ratio (OR) of serum C
      peptide level being associated with ever stroke. RESULTS: A total of 103
      nondiabetic subjects reported having a stroke. Logistic regression analysis
      revealed a high-serum C-peptide level significantly associated with ever stroke
      among nondiabetic subjects (OR: 3.71, 95% confidence interval: 1.78-7.75).
      Meanwhile, in multiple linear regression analysis, serum C-peptide level was
      positively associated with total and regional fat distribution among nondiabetic
      subjects. CONCLUSION: The serum C-peptide level is strongly associated with the
      ever stroke in nondiabetic subjects and significantly associated with total and
      regional body fat distribution.

PMID- 24139411
TI  - The development of quality indicators for the prevention and management of
      postpartum haemorrhage in primary midwifery care in the Netherlands.
AB  - BACKGROUND: At present, there are no guidelines on prevention and management of
      postpartum haemorrhage in primary midwifery care in the Netherlands. The first
      step towards implementing guidelines is the development of a set of quality
      indicators for prevention and management of postpartum haemorrhage for primary
      midwifery supervised (home) birth in the Netherlands. METHODS: A RAND modified
      Delphi procedure was applied. This method consists of five steps: (1) composing
      an expert panel (2) literature research and collection of possible quality
      indicators, (3) digital questionnaire, (4) consensus meeting and (5) critical
      evaluation. A multidisciplinary expert panel consisting of five midwives, seven
      obstetricians and an ambulance paramedic was assembled after applying pre
      specified criteria concerning expertise in various domains relating to primary
      midwifery care, secondary obstetric care, emergency transportation, maternal
      morbidity or mortality audit, quality indicator development or clinical
      guidelines development and representatives of professional organisations.
      RESULTS: After literature review, 79 recommendations were selected for assessment
      by the expert panel. After a digital questionnaire to the expert panel seven
      indicators were added, resulting in 86 possible indicators. After excluding 41
      indicators that panel members unanimously found invalid, 45 possible indicators
      were assessed at the consensus meeting. During critical evaluation 18 potential
      indicators were found to be overlapping and two were discarded due to lack of
      measurability. CONCLUSIONS: A set of 25 quality indicators was considered valid
      for testing in practice.

PMID- 24139412
TI  - Hydroxyurea potentiates the caspase-independent killing of B-cell lines by
      rituximab and GA101.
AB  - Anti-CD20 monoclonal antibodies have revolutionized the treatment of non
      Hodgkin's lymphoma over the last decade. Unfortunately, a significant number of
      patients treated by these antibodies exhibit innate or acquired antibody
      resistance and fail to respond to treatment. Strategies to improve antibody
      function and overcome resistance include the development of new "engineered"
      antibodies and the use of new drug combination therapies. In this report, we show
      that the antimetabolite hydroxyurea significantly enhances the ability of two
      therapeutic monoclonal antibodies to directly kill some human B-cells. The two
      anti-CD20 antibodies studied were a clinically well-established type 1
      therapeutic antibody, namely rituximab and GA101, an antibody representing the
      new breed of type 2 glycoengineered monoclonals. Hydroxyurea specifically
      enhanced the direct caspase-independent killing pathway of both of these
      antibodies as exemplified by the resistance to broad spectrum caspase inhibitors,
      lack of internucleosomal DNA laddering, and lack of activation of caspases 3, 8,
      and 9. Both rituximab and GA101 appear to preferentially kill cells in the G0/G1
      cell cycle phase. One of the many reported effects of hydroxyurea is cell arrest
      in this phase. Arresting antibody-sensitive cells in this stage of the cell cycle
      by means other than hydroxurea also sensitized the cells to caspase-independent
      antibody-mediated death, suggesting that the potentiating effect of hydroxyurea
      may be mediated via its effects upon the cell cycle. The possible combination of
      hydroxyurea and anti-CD20 monoclonal antibodies may offer new possibilities for
      combination therapies in the clinic. 

PMID- 24139413
TI  - MiR-378 inhibits progression of human gastric cancer MGC-803 cells by targeting
      MAPK1 in vitro.
AB  - Gastric cancer (GC) is one of the most common cancers and the leading cause of
      cancer-related deaths globally. The discovery of microRNAs (miRNAs) provides a
      new avenue for GC diagnostic and treatment regiments. Currently, a large number
      of miRNAs have been reported to be associated with the progression of GC, among
      which miR-378 has been examined to be downregulated in GC tissues and several
      cell lines. However, the function of miR-378 on GC cells and the mechanisms were
      less known. Here we found that ectopic expression of miR-378 could inhibit cell
      proliferation, cell cycle progression, cell migration as well as invasion, and
      induced cell apoptosis in GC cell line MGC-803. Moreover, we found that oncogene
      mitogen-activated protein kinase 1 (MAPK1) was a target gene of miR-378 in GC
      cells, and the tumor-suppressive role of miR-378 might be achieved by the direct
      interaction with MAPK1. Taken together, our results showed that miR-378 might act
      as tumor suppressors in GC, and it may provide novel diagnostic and therapeutic
      options for human GC clinical operation in the future. 

PMID- 24139414
TI  - Zinc finger X-chromosomal protein (ZFX) promotes solid agar colony growth of
      osteosarcoma cells.
AB  - Zinc finger X-chromosomal protein (ZFX) is a member of the zinc finger family of
      proteins. The importance of ZFX in several cancer types, including prostate
      cancer, laryngeal squamous cell carcinoma, and glioma, has been addressed.
      However, the role of ZFX in human osteosarcoma remains unknown. Here we
      investigated the phenotype of ZFX knockdown on cell proliferation and in vitro
      tumorigenesis using lentivirus-mediated loss-of-function strategy. The results
      demonstrated that the proliferation and colony formation ability of human
      osteosarcoma Saos-2 and MG63 cells was impaired by ZFX small interfering RNA
      (siRNA)-expressing lentivirus. Moreover, loss of ZFX led to G0/G1 phase cell
      cycle arrest and a significant increase of cells in the sub-G1 fraction,
      indicating that ZFX functions as an oncogene in the malignant proliferation
      process in osteosarcoma. Furthermore, ZFX siRNA may have an antitumorigenic
      effect on osteosarcoma cells. Our findings hold important significance for RNA
      interference-mediated cancer gene therapy for human osteosarcoma. 

PMID- 24139415
TI  - Synergistic effect of 5-azacytidine and NF-kappaB inhibitor DHMEQ on apoptosis
      induction in myeloid leukemia cells.
AB  - Constitutive NF-kappaB activation characterizes a subset of myeloid leukemia (ML)
      cells. Recent reports have indicated that DNA methyltransferase (DNMT) inhibitors
      are alternative candidates for the treatment of ML. However, the optimal use of
      DNMT as a chemotherapeutic agent against ML has yet to be established. In this
      report, we examined the effect of the NF-kappaB inhibitor
      dehydroxymethylepoxyquinomicin (DHMEQ) and its combinational use with the DNMT
      inhibitor 5-azacytidine (AZA) in ML cell lines. DHMEQ alone induced cell death in
      ML cell lines with NF-kappaB activation, although the response varied among the
      cell lines. The addition of DHMEQ enhanced the effect of AZA on the viability and
      apoptosis induction of ML cell lines. The treatment of ML cell lines with AZA
      marginally induced NF-kappaB binding activity, although the treatment induced NF
      kappaB protein. These results indicate the potential usefulness of DHMEQ and its
      combinational use with AZA in the treatment of ML, although the molecular effect
      by AZA on the NF-kappaB pathway awaits further study. 

PMID- 24139416
TI  - Inhibition of lymphatic metastases by a survivin dominant-negative mutant.
AB  - Metastasis is the most lethal attribute of human malignancy. High-level
      expression of survivin is involved in both carcinogenesis and angiogenesis in
      cancer. Previous studies indicate that a mutation of the threonine residue at
      position 34 (Thr34Ala) of survivin generates a dominant-negative mutant that
      induces apoptosis, inhibits angiogenesis, and suppresses highly metastatic breast
      carcinoma in mouse models. We investigated the efficacy of gene therapy with a
      survivin dominant-negative mutant and possible factors related to lymph node
      metastasis. The metastasis rate was compared between each group in order to find
      a survivin-targeted therapy against lymphangiogenesis in its earliest stages. We
      established lymph node metastasis models and treated animals with H22 tumors with
      Lip-mSurvivinT34A (Lip-mS), Lip-plasmid (Lip-P), or normal saline (NS). Eight
      days after the last dose, five randomly chosen mice from each group were
      sacrificed. We detected the apoptotic index, microvessel density (MVD), lymphatic
      microvessel density (LMVD), and the expression of VEGF-D with
      immunohistochemistry. After the remaining animals were sacrificed, we compared
      the tumor-infiltrated lymph nodes in each group. Administration of mSurvivinT34A
      plasmid complexed with cationic liposome (DOTAP/chol) resulted in the efficacious
      inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor
      model. These responses were associated with tumor cell apoptosis, and
      angiogenesis and lymphangiogenesis inhibition. Our results suggested that Lip
      mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and
      lymphangiogenesis, thus suppressing tumor growth and lymphatic metastasis. The
      mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit
      lymphatic metastasis. 

PMID- 24139417
TI  - Cancer stem cell-like cells exist in mucoepidermoid carcinoma cell line MC3.
AB  - Strong evidence for the presence of cancer stem cells (CSCs) in tumors exists.
      CSCs play an important role in the development, invasion, and drug resistance of
      carcinoma. Poorly differentiated mucoepidermoid carcinoma (MEC) is a lethal
      malignancy of human salivary gland tumors. However, whether there are CSCs in MEC
      and their phenotypes remains unclear. We isolated side population (SP) and sphere
      forming cells from the MEC cell line MC3 and identified their characteristics.
      The results showed that sphere-forming assays could enrich stem cell-like cells,
      with this group of cells exhibiting high cloning efficiency, possessing strong
      tumorigenic ability, and highly expressing Oct4 based on PCR and
      immunocytochemistry assays. They also highly expressed CD44 and lowly expressed
      CD24 according to PCR, immunocytochemistry assays, and fluorescence-activated
      cell sorting analysis. Higher cloning efficiency was observed in the SP cells,
      but PCR revealed that the SP and non-SP cells did not statistically differ in
      their expression of ABCG2, Oct4, CD44, and CD24. In spite of these, the findings
      were not conclusive on whether SP cells are stem cell-like cells. In conclusion,
      CSC-like cells do exist in the MC3 cell line, and sphere-forming assays could
      enrich them, sphere-forming and SP cells are not the same kind of cell
      subpopulations, and the characteristics of SP cells need to be further
      investigated. 

PMID- 24139418
TI  - 11th European association for clinical pharmacology and therapeutics congress,
      2013.

PMID- 24139419
TI  - Commentaries on the current treatment of selected neurologic diseases.

PMID- 24139420
TI  - Current and emerging therapies for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder, with a
      rapidly increasing worldwide prevalence. Although no cure for AD has yet been
      found, substantial progress has been made in our understanding of AD
      pathogenesis. This progress has led to the development of numerous promising
      compounds in various stages of clinical testing. In this review, the current
      pharmacologic treatments for AD are discussed in detail, followed by an overview
      of the main experimental strategies that will shape AD therapeutics over the next
      decade. 

PMID- 24139421
TI  - Evaluation of antiplatelet agents for secondary prevention of stroke using mixed
      treatment comparison meta-analysis.
AB  - BACKGROUND: The current guidelines recommend various antiplatelet agents used
      alone or in combination for secondary prevention of noncardioembolic stroke.
      OBJECTIVE: The purpose of this study was to conduct a mixed treatment comparison
      meta-analysis to determine which antiplatelet or combination of antiplatelet
      agents is most efficacious and tolerable in patients with prior stroke. METHODS:
      A comprehensive literature search was conducted in MEDLINE (1945 through March
      2012), EMBASE (1974 through March 2012), and the Cochrane Controlled Trials
      Registry (1975 through April 2012) to identify randomized trials evaluating the
      role of various antiplatelet agents and combinations for the secondary prevention
      of stroke. Key articles were cross-referenced for additional studies. Data were
      screened and evaluated to generate direct and indirect comparisons for recurrent
      stroke and overall hemorrhagic events. Data were reported as rate ratios (RRs)
      and 95% CIs. RESULTS: A total of 24 articles were included in the analysis.
      Eleven antiplatelet regimens were compared in >88,000 patients. The combination
      of acetylsalicylic acid (ASA) plus dipyridamole (DP) was more protective against
      recurrent stroke than ASA alone (RR = 0.78; 95% CI, 0.64-0.93), and no
      differences were found in all other direct and indirect comparisons with active
      treatment. ASA plus DP was associated with more overall hemorrhagic events than
      DP (RR = 1.83; 95% CI, 1.17-2.81), cilostazol (RR = 2.12; 95% CI, 1.21-3.48), and
      triflusal (RR = 1.67; 95% CI, 1.05-2.78) but fewer events than the combination of
      ASA plus clopidogrel (RR = 0.38; 95% CI, 0.25-0.56). The combination of ASA plus
      clopidogrel was associated with an excess of overall hemorrhagic events compared
      with clopidogrel (RR = 2.81; 95% CI, 1.96-4.10), cilostazol (RR = 5.56; 95% CI,
      3.03-9.66), DP (RR = 4.78; 95% CI, 2.80-8.21), sarpogrelate (RR = 3.59; 95% CI,
      1.96-6.45), terutroban (RR = 2.13; 95% CI, 1.21-3.61), ticlopidine (RR = 2.80;
      95% CI, 1.69-5.00), and triflusal (RR = 4.36; 95% CI, 2.62-7.81). CONCLUSION: We
      found that ASA plus DP was more protective than ASA alone for preventing
      recurrent stroke; however, no difference was found between most direct and
      indirect comparisons of antiplatelet agents and combinations. More overall
      hemorrhagic events seemed to occur with the combination of ASA and clopidogrel
      than with other treatments. Selection of antiplatelet therapy for the secondary
      prevention of stroke must be individualized according to patient comorbidities,
      including risk of stroke recurrence and bleeding.

PMID- 24139422
TI  - Treatment patterns in disease-modifying therapy for patients with multiple
      sclerosis in the United States.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) whose disease activity is
      inadequately controlled with a platform therapy (interferon beta or glatiramer
      acetate [GA]) may switch to another platform therapy or escalate therapy to
      natalizumab or fingolimod, which were approved in the US in 2006 and 2010,
      respectively. OBJECTIVE: The objective of this study was to describe treatment
      patterns in patients with multiple sclerosis (MS) in the United States who were
      followed for 2 years after initiating a disease-modifying therapy (DMT). METHODS:
      A retrospective observational cohort study was conducted to examine treatment
      patterns of initial DMT use (on initial therapy for 2 years with and without gaps
      of >= 60 days, medication switching, and discontinuation) among patients with MS
      who initiated a platform therapy (interferon-beta or glatiramer acetate) or
      natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim
      was the index. Eligible patients were identified in the MarketScan Commercial and
      Medicare Supplemental databases based on continuous enrollment for 6 months
      before (preindex period) and 24 months after their index date, with a diagnosis
      of MS and no claim for a previous DMT in the 6-month preindex period.
      Demographics at index and clinical characteristics during the preindex period
      were also analyzed. RESULTS: A total of 6181 MS patients were included, with 5735
      (92.8%) starting on platform therapy. Natalizumab initiators were more likely to
      stay on index therapy (32.3% vs 16.9%, P < 0.001) and have fewer treatment gaps
      of >= 60 days (44.8% vs 55.3%, P < 0.001) compared with platform initiators. In
      addition, natalizumab initiators were less likely to switch treatment (13.9% vs
      19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P < 0.001)
      compared with platform initiators. Nearly 79% of platform initiators who switched
      went to another platform therapy. Approximately two thirds of patients who
      switched to a third DMT (n = 130) switched to another platform therapy. A total
      of 9% of natalizumab and platform initiators discontinued DMT within the 2 years.
      CONCLUSIONS: Most MS patients initiating DMT started on platform therapy.
      Natalizumab initiators tended to stay on index therapy, have fewer treatment
      gaps, and switch less than platform initiators in the 2 years after treatment
      initiation. Switching between platform therapies is common despite evidence that
      MS patients on platform therapy may benefit from switching to natalizumab.

PMID- 24139423
TI  - Antiparkinson drug use and adherence in medicare part D beneficiaries with
      Parkinson's disease.
AB  - BACKGROUND: Antiparkinson drugs (APDs) are the mainstay of managing Parkinson's
      disease (PD). However, there is paucity of evidence documenting patterns of APD
      use and examining factors associated with adherence to APDs. OBJECTIVES: Our goal
      was to provide updated, comprehensive population-based data on APD use and
      adherence and to examine characteristics associated with adherence behaviors.
      METHODS: We analyzed data from 7583 beneficiaries with PD who had >= 2 APD
      prescription fills and were continuously enrolled in Medicare Parts A, B, and D
      for up to 19 months (from June 1, 2006, through December 31, 2007) or until death
      in 2007. We assessed 5 patterns of APD use: (1) concurrent use of >= 2 APD
      classes for >= 30 days; (2) switching of APDs from 1 to another; (3) augmentation
      of the existing regimen with a new APD; (4) duration of therapy, defined as days
      of APD treatment; and (5) adherence measured by using the medication possession
      ratio (MPR). We corrected for sample selection bias inherent in patients' self
      selection into either a Part D plan or a Medicare Advantage Prescription Plan by
      using Heckman's 2-stage procedures. RESULTS: APD users were pre-dominantly aged
      >= 65 years (93.6%), female (59.9%), and white (89.3%). Almost one half (43.2%)
      of APD users concurrently used >= 2 APD classes. One in 4 APD users experienced
      changes in their APD regimen, with 16.4% switching medications and 21.1%
      augmenting their current regimen. Three quarters of APD users had therapy lasting
      >= 436 days (75.3%) and an MPR >= 0.8 (72.7%). Multivariate analyses revealed
      that patients aged >= 65 years, of non-white race, non-low-income subsidy
      recipients, late Part D enrollees, cognitively impaired, highly comorbid, and who
      experienced multiple changes in APD therapy were less likely to adhere to APD
      therapy. We were able to generalize our findings to all Part D enrollees by
      correcting for sample selection bias using the Heckman approach. These population
      level, generalizable observations provide better understanding of APD use and
      adherence and assist in the design of interventions for poor adherence.
      Limitations include cross-sectional study design and constraints in
      administrative data that preclude measurement of other potential factors related
      to adherence. CONCLUSIONS: A substantial proportion of these Medicare
      beneficiaries with PD used multiple APDs concurrently, experienced switching
      and/or augmentation of APDs, and had poor adherence to APDs. Patient
      characteristics and clinical and drug-related factors were important predictors
      of APD adherence.

PMID- 24139424
TI  - Tolerability and pharmacokinetics of delayed-release dimethyl fumarate
      administered with and without aspirin in healthy volunteers.
AB  - BACKGROUND: Delayed-release dimethyl fumarate (DR-DMF) has cytoprotective and
      antiinflammatory properties and has recently been approved in the United States
      as an oral treatment for relapsing forms of multiple sclerosis. The most common
      adverse events associated with DR-DMF are flushing and gastrointestinal (GI)
      events, the incidences of which diminish over time. OBJECTIVE: The purpose of
      this study was to evaluate the tolerability and pharmacokinetic (PK) profile of
      DR-DMF with or without concomitant acetylsalicylic acid (aspirin), a
      cyclooxygenase inhibitor. METHODS: Healthy volunteers (N = 56) were randomized to
      receive different dosing regimens of DR-DMF or matching placebo with or without
      pretreatment with 325 mg aspirin for 4 days. Plasma levels of the active
      metabolite monomethyl fumarate were assessed on days 1 and 4. Flushing and GI
      events were assessed using patient-reported scales. Potential flushing mediators
      were explored. RESULTS: DR-DMF showed a safety, tolerability, and PK profile
      consistent with previous clinical experience, with no evidence of accumulation.
      Pretreatment with aspirin had no effect on the primary PK parameters, AUC0-10h,
      or Cmax. Flushing severity, assessed by 2 subject-reported rating scales, was
      generally mild and was rated highest at the start of treatment. Pretreatment with
      aspirin reduced flushing incidence and intensity without affecting GI events or
      the PK profile of DR-DMF. In some DR-DMF-treated individuals, plasma
      concentrations of a prostaglandin D2 (PGD2) metabolite were increased.
      CONCLUSIONS: In healthy volunteers, DR-DMF was well tolerated over 4 days of
      dosing, with a PK profile consistent with that previously reported and no
      evidence of accumulation. Aspirin pretreatment reduced the incidence and
      intensity of flushing without affecting GI events or the DR-DMF PK profile.
      Elevated levels of PGD2 in some DR-DMF-treated individuals suggest that flushing
      may be, at least in part, prostaglandin mediated. ClinicalTrials.gov identifier:
      ID: NCT01281111.

PMID- 24139425
TI  - Discharge of adolescents with mental health problems against medical advice:
      findings from adult mental health inpatient facilities across Ontario, Canada.
AB  - Little is known about discharge against medical advice (DAMA) among adolescents
      with mental health problems. The objective of this study was to examine the
      prevalence of DAMA and provide some insight into the factors that influence DAMA
      among adolescents with mental health problems using a large dataset from Ontario,
      Canada. Data on 1811 adolescents aged 14-18 years who were discharged from adult
      mental health beds between October 2005 and March 2010 were analyzed using
      logistic regression. Of the 1811 discharges in the sample, 78(4.3%) were against
      medical advice. In the multivariate model, older age, having limited insight or
      no insight into mental illness, provisional DSM-IV diagnoses of substance-related
      disorders, eating disorders, and personality disorders increased the odds of
      DAMA. Length of stay was negatively associated with DAMA. The findings of this
      study highlight the importance of completing comprehensive assessments at the
      time of admission to identify adolescents who are at risk of treatment refusal
      and provide timely intervention to prevent DAMA. 

PMID- 24139426
TI  - Epidemiological features of hand-foot-and-mouth disease in Shenzhen, China from
      2008 to 2010.
AB  - This study analysed the spatio-temporal distribution and propagation of hand-foot
      and-mouth disease (HFMD) in Shenzhen from 2008 to 2010. Specifically, we examined
      the epidemiological data, temporal distribution and spatial distribution, and
      then the relationship between meteorological, social factors and the number of
      reported HFMD cases was analysed using Spearman's rank correlation. Finally, a
      geographically weighted regression model was constructed for the number of
      reported HFMD cases in 2009. It was found that three independent variables, i.e.
      the number of reported HFMD cases in 2008 and, annual average temperature and
      precipitation, had different spatial impacts on the number of reported HFMD cases
      in 2009. In addition, these variables accounted for the propagation mechanism of
      HFMD in the centre and east of Shenzhen, where the high incidence rate areas are
      located. These results will be of great help in understanding the spatio-temporal
      distribution of HFMD and developing approaches to prevent this disease.

PMID- 24139427
TI  - The relationship between early atherosclerosis and endothelial dysfunction in
      type 1 diabetic patients as evidenced by measurement of carotid intima-media
      thickness and soluble CD146 levels: a cross sectional study.
AB  - BACKGROUND: Detection of early vascular changes prior to clinical manifestations
      of atherosclerosis, such as increased arterial carotid intima-media thickness
      (CIMT) and impaired endothelial function is of paramount importance for early
      identification of subjects at increased risk of accelerated atherosclerosis. The
      present study was designed to evaluate the relationship between early
      atherosclerosis and endothelial dysfunction in type 1 diabetic patients based on
      measurements of CIMT and soluble CD146 (sCD146) levels. METHODS: Thirty-seven
      patients with type 1 diabetes, 14 males (37.8%) and 23 females (62.2%), of mean
      (SD) age 26.2 (4.1) years admitted to the outpatient diabetes clinic at Okmeydani
      Training and Research Hospital, Istanbul, between January 2008 and December 2012,
      and 37 healthy controls, 16 males (43.2%) and 21 females (56.8%), of mean (SD)
      age 25.8 (3.1) years, selected from relatives of patients, were included.
      Anthropometric measures; fasting plasma glucose; and serum HbA1c, total
      cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and creatinine
      concentrations were compared, as were CIMT and serum sCD146. RESULTS: Mean (SD)
      sCD146 levels were significantly higher in patients than in controls (314.6
      (141.9) ng/ml vs. 207.8 (34.5) ng/ml, p = 0.001), but mean (SD) CIMT did not
      differ (0.5 (0.1) mm vs. 0.4 (0.1) mm). ROC curves for sCD146 significantly
      differed in differentiating type 1 diabetics from healthy controls (p = 0.0047)
      with a significantly higher percentage of patients than controls having sCD146
      levels >260 ng/ml (21/37 (56.8%) vs. 2/37 (5.4%), p = 0.00011). CONCLUSION: Our
      findings emphasize that sCD146 levels may be a more sensitive marker than CIMT
      for earlier identification of type 1 diabetic patients at high risk for
      atherosclerosis.

PMID- 24139428
TI  - Treatment of wounds colonized by multidrug resistant organisms in immune
      compromised patients: a retrospective case series.
AB  - BACKGROUND: Immune-compromised patients incur a high risk of surgical wound
      dehiscence and colonization by multidrug resistant organisms. Common treatment
      has been debridement and spontaneous secondary healing.We report on the results
      obtained in nine such patients whose wounds were treated by debridement, negative
      pressure dressing and direct closure. METHODS: All immune-compromised patients
      referred to our Institution between March 1, 2010 and November 30, 2011 for
      dehiscent abdominal wounds growing multidrug resistant organisms were treated by
      serial wound debridements and negative pressure dressing. They were primarily
      closed, despite positive microbiological cultures, when clinical appearance was
      satisfactory.As a comparison, records from patients treated between March 1, 2008
      and February 28, 2010 who, according to our Institution's policy at that time,
      had been left to heal by secondary intention, were retrieved and examined.
      RESULTS: Nine patients were treated by direct wound closure, five had been
      treated previously by secondary intention healing.Overall, ten patients had
      received liver transplant, 1 kidney transplant, 1 was HIV infected, 1 suffered
      from multi-organ failure, 1 was undergoing hemodialysis.Wound dehiscence involved
      skin and subcutaneous layers in all patients, in two the muscular layer was also
      involved.Mean healing time was significantly shorter in patients treated more
      recently by primary intention in comparison with historical patients (28 vs 81
      days). The only complication observed was a small superficial abscess that
      developed around a non-absorbable stitch 10 months after closure in a patient
      treated by primary closure. CONCLUSIONS: According to our results, fast healing
      can be safely obtained by closure of a clinically healthy wound, despite growth
      of multidrug resistant organisms, even in immune-compromised patients.

PMID- 24139429
TI  - Photolytic and photocatalytic degradation of surface oil from the Deepwater
      Horizon spill.
AB  - The photochemical behavior of Deepwater Horizon oil collected from the surface of
      the Gulf of Mexico was studied. Thin oil films on water were subjected to
      simulated sunlight, and the resulting chemical and optical changes were observed.
      Polycyclic aromatic hydrocarbons (PAHs) showed substantial photodegradation, with
      larger PAHs being more rapidly decomposed. About 60% of the fluorescence at the
      excitation and emission maxima was observed with 12h of simulated solar
      irradiation equivalent to approximately 3d of sunlight. Synchronous scan
      fluorescence measurements showed 80-90% loss of larger PAHs with 12h of simulated
      solar irradiation. Absorbance of the oil decreased by only 20% over the same time
      period. Alkanes showed no significant photochemical losses. After irradiation,
      the toxicity of water in contact with the oil significantly increased, presumably
      due to the release of water soluble photoproducts that were toxic. Photocatalyst
      addition resulted in enhanced degradation rate for PAHs, and toxicity of the
      aqueous layer was altered in the presence of photocatalysts added to the oil
      film. Photochemistry is an important pathway for degradation of large PAHs, which
      are typically resistant to biodegradation. 

PMID- 24139430
TI  - Effect of DA-6 and EDTA alone or in combination on uptake, subcellular
      distribution and chemical form of Pb in Lolium perenne.
AB  - The effects of growth-promoting hormone diethyl aminoethyl hexanoate (DA-6) and
      EDTA, either alone or in combination applied to original soil or lead (Pb) spiked
      soil on Pb phytoextraction, subcellular distribution and chemical forms in Lolium
      perenne were studied. EDTA addition alone significantly reduced plant biomass
      though it increased Pb accumulation (P<0.05). Foliar spray of DA-6 alone
      increased both plant biomass and Pb accumulation (P<0.05), with 10MUM DA-6 being
      the most effective. DA-6 combined with EDTA compensated the adverse effect of the
      latter on plant growth, and resulted in a synergistic effect on Pb uptake and
      translocation, with the maximum accumulation occurring in the EDTA+10MUM DA-6
      treatment. At the subcellular level, about 35-66% of Pb was distributed in cell
      wall and 21-42% in soluble fraction, with a minority present in cellular
      organelles fraction. EDTA addition alone increased the proportion of Pb in
      soluble and cellular organelles fraction, while DA-6 detoxified Pb in plant by
      storing additional Pb in cell wall, and 10MUM DA-6 was the most effective. Of the
      total Pb in plant shoot, 27-52% was NaCl extractable, 22-47% HAc extractable,
      followed by other fractions. Contrary to EDTA, DA-6 significantly decreased Pb
      migration in plant. These results suggest that Pb fixation by pectates and
      proteins in cell wall and compartmentalization by vacuole might be responsible
      for Pb detoxification in plant, and the combined use of EDTA and 10MUM DA-6
      appears to be optimal for improving the remediation efficiency of L. perenne for
      Pb contaminated soil. 

PMID- 24139431
TI  - Drug-excipient compatibility studies in binary mixtures of avobenzone.
AB  - During preformulation studies of cosmetic/pharmaceutical products, thermal
      analysis techniques are very useful to detect physical or chemical
      incompatibilities between the active and the excipients of interest that might
      interfere with safety and/or efficacy of the final product. Differential scanning
      calorimetry (DSC) was used as a screening technique for assessing the
      compatibility of avobenzone with some currently used cosmetic excipients. In the
      first phase of the study, DSC was used as a tool to detect any interaction. Based
      on the DSC results alone, cetearyl alcohol, isopropyl myristate, propylparaben,
      diethylhexyl syringylidene malonate, caprylic capric triglyceride, butylated
      hydroxytoluene (BHT), glycerin, cetearyl alcohol/ceteareth 20, cetearyl
      alcohol/sodium lauryl sulfate/sodium cetearyl sulfate, and paraffinum liquidum
      exhibit interaction with avobenzone. Stressed binary mixtures (stored at 50
      degrees C for 15 days) of avobenzone and excipients were evaluated by high
      performance liquid chromatography. Binary mixtures were further investigated by
      infrared (IR) spectroscopy. Based on DSC, isothermal stress testing, and fourier
      transform infrared results; avobenzone is incompatible with caprylic capric
      triglyceride, propylparaben, and BHT. 

PMID- 24139432
TI  - Moisturizing effect of topical cosmetic products applied to dry skin.
AB  - One of the complications of "diabetes mellitus" is termed diabetic foot syndrome,
      the first symptoms of which include changes in the skin's condition and
      properties. The skin becomes dehydrated, dry, and prone to excessive formation of
      the horny layer, its barrier function becoming weakened. This function can be
      restored by applying suitable cosmetic excipients containing active substances.
      The aim of this study was to evaluate and compare the effects of commercially
      available cosmetic products (CPs) designed for the care of diabetic foot, through
      a group of selected volunteers using noninvasive bioengineering methods.
      Statistical surveys (p < 0.05) evaluated these CPs as regards to their hydration
      effect and barrier properties. Special attention was devoted to CPs with the
      declared content of 10% urea, and that the influence of this preparation's
      ability to hydrate and maintain epidermal water in the epidermis was confirmed. 

PMID- 24139433
TI  - Formulation strategies to modulate the topical delivery of anti-inflammatory
      compounds.
AB  - The aim of this study was to assess the ability of some vehicles (emulsion and
      emulgel), containing hydrogenated lecithin as penetration enhancer, in increasing
      the percutaneous absorption of the two model compounds dipotassium
      glycyrrhizinate (DG) and stearyl glycyrrhetinate (SG). Furthermore SG-loaded
      solid lipid nanoparticles (SLNs) were prepared and the effect of this vehicle on
      SG permeation profile was evaluated as well. Percutaneous absorption has been
      studied in vitro, using excised human skin membranes (i.e., stratum corneum
      epidermis or [SCE]), and in vivo, determining their anti-inflammatory activity.
      From the results obtained, the use of both penetration enhancers and SLNs
      resulted in being valid tools to optimize the topical delivery of DG and SG. Soy
      lecithin guaranteed an increase in the percutaneous absorption of the two
      activities and a rapid anti-inflammatory effect in in vivo experiments, whereas
      SLNs produced an interesting delayed and sustained release of SG.

PMID- 24139434
TI  - Determination of physicochemical properties of delipidized hair.
AB  - Using various physicochemical methods of analysis, we examined human hair in its
      virgin and delipidized state. Free lipids were removed by a solvent extraction
      technique (covalently bound lipids were not removed) using a series of solvents
      with varying polarity. We analyzed the surface properties of hair by conducting
      mechanical combing and dynamic contact angle analysis. In addition, we used
      inverse gas chromatography surface energy analysis to explore the chemical
      composition of the hair surface based on interactions of various nonpolar and
      polar probes with biological molecules residing on the hair surface. Further, we
      investigated the importance that free lipids play in the internal structural
      properties of hair using dynamic scanning calorimetry and tensile strength
      measurements. The microstructure of the hair surface was probed by atomic force
      microscopy, whereas the lipid content of hair's morphological components was
      determined by infrared spectroscopic imaging. We also monitored the water
      management properties of virgin and delipidized hair by dynamic vapor sorption,
      which yielded unique water sorption isotherms for each hair type. Using all these
      techniques, differences were found in the chemical composition and physical
      behavior of virgin and delipidized hair. To better understand the influence of
      hair lipid composition on hair styling treatments, we conducted mechanical
      analyses of hair shaped into omega loops to determine the stiffness, elasticity,
      and flexibility of hair-polymer assemblies. Although there were no discernible
      differences between untreated virgin and delipidized hair, in terms of stiffness
      and elasticity, we found that treatment with hair styling agents produced
      different effects depending on the hair type used. Likewise, streaming potential
      measurements were carried out to monitor the binding capacity of rinse-off
      treatments on virgin and delipidized hair. Using this technique, we monitored the
      surface potential of hair and found significant differences in the binding
      behavior of cationic polymers and surfactants (polyquaternium-55 and quaternium
      26) on both hair types. 

PMID- 24139435
TI  - Sensory characterization of virgin olive oil-based cosmetic creams.
AB  - The influence of olive oil concentration and sensory profile on the odor of
      virgin olive oil-based cosmetic creams was studied. Four olive oils were selected
      on the basis of different intensities of positive and defective odor attributes:
      two extra virgin olive oils, one virgin olive oil, and one ordinary virgin olive
      oil. Thirty cosmetic creams were prepared, by both cold and hot processing
      methods, using each of the above oils at concentrations of 3%, 5%, and 10%, in
      addition to mineral oil controls. A trained sensory panel evaluated the
      fruitiness and defectiveness intensities in the odor of creams, using
      unstructured 10-cm scales ranging from "none at all" to "much." The fruity and
      defective attributes perceived in the odor of creams were significantly
      influenced by the sensory profile of the starting olive oil, oil concentration,
      and preparation method. Overall, these findings suggest that virgin olive oils of
      only slightly fruity odor may be conveniently used for the preparation of cold
      processed cosmetic creams, whereas ordinary virgin olive oils appear to be
      suitable for the preparation of cosmetic creams only by hot processing of the
      emulsion at a low oil concentration. 

PMID- 24139436
TI  - Determination of hinokitiol in skin lotion by high-performance liquid
      chromatography-ultraviolet detection after precolumn derivatization with 4-fluoro
      7-nitro-2,1,3-benzoxadiazole.
AB  - Hinokitiol, a potent, broad-spectrum antibacterial agent, is a component of
      various personal care products. In this study, the concentration of hinokitiol in
      skin lotion was analyzed by means of high-performance liquid chromatography
      ultraviolet detection (380 nm) after precolumn derivatization with 4-fluoro-7
      nitro-2,1, 3-benzoxadiazole (NBD-F). A standard curve was obtained after
      derivatization of the authentic compound with NBD-F in borate buffer (pH 9.0) at
      60 degrees C for 10 min. The retention time of NBD-hinokitiol was 7.2 min. The
      calibration plot was linear in the range of 0.2 to 4 mg/ml with an r2 value of
      0.9985, and the lower limit of detection was 0.05 MUg/ml (at a signal-to-noise
      ratio of 3, absolute amount of 0.33 ng/20 MUl injection). The coefficient of
      variation was less than 9.4%. It was found that the amount of hinokitiol in the
      tested skin lotion was 194 +/- 14 MUg/ml (range: 180-212 MUg/ml). Recovery in
      addition-recovery tests was within the range of 84.5% to 98.0%. This system is
      simple, sensitive, and convenient, and should be suitable for routine quality
      assessment of personal care products containing hinokitiol. 

PMID- 24139437
TI  - Application of Purpald(r) for determination of 3-cyclohexene-1-carboxaldehyde and
      hydroxyisohexyl 3-cyclohexene carboxaldehyde.
AB  - A spectrophotometric method for determination of 3-cyclohexene-1-carboxaldehyde
      and hydroxyisohexyl 3-cyclohexene carboxaldehyde was developed. This procedure is
      based on the reaction of carbonyl compounds with the selective derivatization
      reagent Purpald(r) in alkaline solution. The product of reaction is a colored
      compound with maximum absorption at 538 nm. The linear relationship is in the
      range of (2.5-30) * 10-5 mol.l-1 for 3-cyclohexene-1-carboxaldehyde and (2.0-20)
      * 10-5 mol.l-1 for hydroxyisohexyl 3-cyclohexene carboxaldehyde. The proposed
      method was successfully used for determination of hydroxyisohexyl 3-cyclohexene
      carboxaldehyde in a cosmetic product.

PMID- 24139438
TI  - Oxytocin: an unexpected risk for cardiologic and broncho-obstructive effects, and
      allergic reactions in susceptible delivering women.
AB  - Oxytocin (Sintocynon) is considered an uncommon cause of severe allergic
      reactions during delivery. We have recently shown that allergic sensitization to
      latex might constitute an important predisposing risk factor for anaphylaxis
      after the first infusion of oxytocin during delivery.Some oxytocin cardiovascular
      activities such as lowering blood pressure, negative cardiac inotropy and
      cronotropy, parasympathetic neuromodulation, vasodilatation etc. can induce
      significant side effects mimicking cardiac anaphylaxis, and constitute an
      additional differential diagnostic problem in delivering women with suspected or
      real allergic background. Finally, some ex vivo models have shown that oxytocin,
      under pro-inflammatory cytokines stimulation, such as those occurring in asthma,
      may induce contraction of smooth muscle and airway narrowing.This background
      suggests that allergic sensitization to latex allergens constitutes a significant
      but underestimated risk factor for triggering severe systemic reactions after the
      infusion of oxytocin and, consequently, there is a need of particular attention
      in managing delivering women suffering from latex allergy and bronchial asthma.
      An accurate anamnestic, clinical and diagnostic evaluation, latex-free
      anesthesiological setting, use of oxytocin-alternative agents and, if necessary,
      a drug premedication are likely to reduce the risk of anaphylactic/broncho
      obstructive reactions in these women. 

PMID- 24139439
TI  - Measuring the impact of caregiving on informal carers: a construct validation
      study of the CarerQol instrument.
AB  - BACKGROUND: Informal caregivers provide a significant part of the total care
      needed by ill or disabled persons. Although informal care is often the preferred
      option of those who provide and those who receive informal care, caring can
      nevertheless be very straining. This study investigates construct validation of
      an instrument of the impact of caregiving, the CarerQol. METHODS: Data was
      collected among adult caregivers (n = 1,244) selected from the general population
      using an online questionnaire in October 2010, in the Netherlands. The CarerQol
      measures and values the impact of informal care. The CarerQol measures subjective
      burden (CarerQol-7D) and well-being (CarerQol-VAS). Construct validation
      comprised clinical, convergent and discriminative validity tests. RESULTS:
      Clinical validity was supported by statistically significant associations of
      CarerQol-VAS and caregivers' health, income and employment status, care
      recipients' health, and the relationship between caregiver and care recipient.
      Convergent validity was supported by positive associations of CarerQol-VAS with
      the two positive CarerQol-7D dimensions (fulfillment and support) and negative
      associations with the five negative CarerQol-7D dimensions (relational problems,
      mental health problems, problems combining daily activities, financial problems
      and physical health problems). Moreover, CarerQol-VAS was negatively associated
      with other instruments measuring caregiving burden. CONCLUSIONS: Construct
      validity tests in a large, heterogeneous sample of caregivers show that the
      CarerQol validly measures the impact of caregiving. The CarerQol can be used in
      informal care research and economic evaluations of health care interventions.
      Hence, its use can facilitate informed decision making in health care.

PMID- 24139440
TI  - Cervical pain and swelling due to an autonomous adenoma of the thyroid in an
      adolescent girl.

PMID- 24139441
TI  - Non-high-density lipoprotein cholesterol: distribution and prevalence of high
      serum levels in children and adolescents: United States National Health and
      Nutrition Examination Surveys, 2005-2010.
AB  - OBJECTIVES: To estimate age-related changes for serum concentration of non-high
      density lipoprotein cholesterol (HDL-C), describe non-HDL-C distribution, and
      examine the prevalence of high non-HDL-C levels in children and adolescents by
      demographic characteristics and weight status. STUDY DESIGN: Data from 7058
      participants ages 6-19 years in the 2005-2010 National Health and Nutrition
      Examination Surveys were analyzed. A high level of non-HDL-C was defined as a non
      HDL-C value >= 145 mg/dL. RESULTS: Locally weighted scatterplot smoothing
      smoothed curves showed that non-HDL-C levels increased from 101 mg/dL at age 6 to
      111 mg/dL at age 10, decreased to 101 mg/dL at age 14, and then increased to 122
      mg/dL at age 19 in non-Hispanic white males. Non-HDL-C levels generally were
      greater in female than male subjects, lower in non-Hispanic black subjects, and
      similar in male and slightly lower in female Mexican American subjects, compared
      with non-Hispanic white subjects. The overall mean was 108 (SE 0.5), and the
      percentiles were 67 (5th), 74 (10th), 87 (25th), 104 (50th), 123 (75th), 145
      (90th), and 158 (95th) mg/dL. Mean and percentiles were greater among age groups
      9-11 and 17-19 years than others and greater among non-Hispanic white than non
      Hispanic black subjects. The prevalence of high non-HDL-C was 11.8% (95% CI 9.9%
      14.0%) and 15.0% (95% CI 12.9%-17.3%) for the age groups 9-11 and 17-19,
      respectively. It varied significantly by race/ethnicity and overweight/obesity
      status. CONCLUSION: Non-HDL-C levels vary by age, sex, race/ethnicity, and weight
      classification status. Evaluation of non-HDL-C in youth should account for its
      normal physiologic patterns and variations in demographic characteristics and
      weight classification.

PMID- 24139442
TI  - A prospective study of sudden unexpected infant death after reported
      maltreatment.
AB  - OBJECTIVE: To examine whether infants reported for maltreatment face a heightened
      risk of sudden infant death syndrome (SIDS) and other leading causes of sudden
      unexpected infant death (SUID). STUDY DESIGN: Linked birth and infant death
      records for all children born in California between 1999 and 2006 were matched to
      administrative child protection data. Infants were prospectively followed from
      birth through death or 1 year of age. A report of maltreatment was modeled as a
      time-varying covariate; risk factors at birth were included as baseline
      covariates. Multivariable competing risk survival models were used to estimate
      the adjusted relative hazard of postneonatal SIDS and other SUID. RESULTS: A
      previous maltreatment report emerged as a significant predictor of SIDS and other
      SUID. After adjusting for baseline risk factors, the rate of SIDS was more than 3
      times as great among infants reported for possible maltreatment (hazard ratio:
      3.22; 95% CI: 2.66, 3.89). CONCLUSION: Infants reported to child protective
      services have a heightened risk of SIDS and other SUID. Targeted services and
      improved communication between child protective services and the pediatric health
      care community may enhance infant well-being and reduce risk of death.

PMID- 24139443
TI  - Cellulose synthases: new insights from crystallography and modeling.
AB  - Detailed information about the structure and biochemical mechanisms of cellulose
      synthase (CelS) proteins remained elusive until a complex containing the
      catalytic subunit (BcsA) of CelS from Rhodobacter sphaeroides was crystalized.
      Additionally, a 3D structure of most of the cytosolic domain of a plant CelS
      (GhCESA1 from cotton, Gossypium hirsutum) was produced by computational modeling.
      This predicted structure contributes to our understanding of how plant CelS
      proteins may be similar and different as compared with BcsA. In this review, we
      highlight how these structures impact our understanding of the synthesis of
      cellulose and other extracellular polysaccharides. We show how the structures can
      be used to generate hypotheses for experiments testing mechanisms of glucan
      synthesis and translocation in plant CelS. 

PMID- 24139444
TI  - Systems analysis of metabolic phenotypes: what have we learnt?
AB  - Flux is one of the most informative measures of metabolic behavior. Its
      estimation requires integration of experimental and modeling approaches and,
      thus, is at the heart of metabolic systems biology. In this review, we argue that
      flux analysis and modeling of a range of plant systems points to the importance
      of the supply of metabolic inputs and demand for metabolic end-products as key
      drivers of metabolic behavior. This has implications for metabolic engineering,
      and the use of in silico models will be important to help design more effective
      engineering strategies. We also consider the importance of cell type-specific
      metabolism and the challenges of characterizing metabolism at this resolution. A
      combination of new measurement technologies and modeling approaches is bringing
      us closer to integrating metabolic behavior with whole-plant physiology and
      growth. 

PMID- 24139445
TI  - A modeling approach to compute modification of net joint forces caused by coping
      movements in obstetric brachial plexus palsy.
AB  - BACKGROUND: Many disorders of the musculoskeletal system are caused by modified
      net joint forces resulting from individual coping movement strategies of patients
      suffering from neuromuscular diseases. Purpose of this work is to introduce a
      personalized biomechanical model which allows the calculation of individual net
      joint forces via inverse dynamics based on anthropometry and kinematics of the
      upper extremity measured by 3D optoelectronical motion analysis. METHODS: The
      determined resulting net joint forces in the anatomical axis of movement may be
      used to explain the reason for possible malfunction of the musculoskeletal
      system, especially joint malformation. For example the resulting net joint forces
      in the humerothoracic joint from simulations are compared to a sample of children
      presenting obstetric brachial plexus palsy showing an internal shoulder rotation
      position and a sample of healthy children. RESULTS: The results presented from
      the simulation show that an increased internal shoulder rotation position leads
      to increased net joint forces in the humerothoracic joint. A similar behavior is
      presented for the subjects suffering from brachial plexus palsy with an internal
      shoulder rotation position. CONCLUSIONS: The increased net joint forces are a
      possible reason for joint malformation in the humerothoracic joint caused by
      coping movements resulting from neuromuscular dysfunction as stated in
      literature.

PMID- 24139446
TI  - [International Atherosclerosis Society guidelines for management of
      dyslipidemia].

PMID- 24139448
TI  - Jolt accentuation of headache and other clinical signs: poor predictors of
      meningitis in adults.
AB  - Jolt accentuation or exacerbation of a baseline headache with horizontal rotation
      of the neck is a physical finding believed to assess for meningeal irritation. We
      conducted a prospective observational study of neurologically intact emergency
      department (ED) patients undergoing lumbar puncture in 2 inner city academic EDs
      to validate the sensitivity and specificity of jolt accentuation and to assess
      the sensitivity and specificity of Kernig sign, Brudzinski sign, and nuchal
      rigidity, in predicting cerebrospinal fluid (CSF) pleocytosis in individuals
      being assessed for meningitis. Adult patients 18 years and older undergoing
      lumbar puncture between 2006 and 2009 were approached for consent. Exclusions
      included inability to consent and altered mental status. Physicians were asked to
      answer a questionnaire of physical examination findings before receiving CSF
      results. The primary outcome was the presence or absence of pleocytosis, defined
      as greater than or equal to 5 cells/high-power field in the fourth CSF tube. We
      calculated descriptive statistics and tests of diagnostic accuracy. A total of
      230 patients consented for participation and had CSF white blood cell counts
      recorded. Forty-seven individuals (20%) had pleocytosis. A total of 197 patients
      had headache and were, hence, eligible for jolt accentuation assessment. For
      pleocytosis, the sensitivity of jolt accentuation was 21%, Kernig sign was 2%,
      Brudzinski sign was 2%, and nuchal rigidity was 13%. The specificity of jolt
      accentuation was 82%, Kernig sign was 97%, Brudzinski sign was 98%, and nuchal
      rigidity was 80%. Jolt accentuation in our cohort was poorly predictive of
      pleocytosis and insensitive. The presence of Kernig sign, Brudzinski sign, or
      nuchal rigidity has moderate positive but no negative predictive value for
      pleocytosis.

PMID- 24139447
TI  - Maternal adverse effects of different antenatal magnesium sulphate regimens for
      improving maternal and infant outcomes: a systematic review.
AB  - BACKGROUND: Antenatal magnesium sulphate, widely used in obstetrics to improve
      maternal and infant outcomes, may be associated with adverse effects for the
      mother sufficient for treatment cessation. This systematic review aimed to
      quantify maternal adverse effects attributed to treatment, assess how adverse
      effects vary according to different regimens, and explore women's experiences
      with this treatment. METHODS: Bibliographic databases were searched from their
      inceptions to July 2012 for studies of any design that reported on maternal
      adverse effects associated with antenatal magnesium sulphate given to improve
      maternal or infant outcomes. Primary outcomes were life-threatening adverse
      effects of treatment (death, cardiac arrest, respiratory arrest). For randomised
      controlled trials, data were meta-analysed, and risk ratios (RR) pooled using
      fixed-effects or random-effects models. For non-randomised studies, data were
      tabulated by design, and presented as RR, odds ratios or percentages, and
      summarised narratively. RESULTS: A total of 143 publications were included (21
      randomised trials, 15 non-randomised comparative studies, 32 case series and 75
      reports of individual cases), of mixed methodological quality. Compared with
      placebo or no treatment, magnesium sulphate was not associated with an increased
      risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate
      significantly increased the risk of 'any adverse effects' overall (RR 4.62, 95%
      CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse
      effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup
      differences were observed (between indications for use and treatment regimens).
      In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose
      regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI
      0.01-0.39, 126 women). Adverse effect estimates from studies of other designs
      largely supported data from randomised trials. Case reports supported an
      association between iatrogenic overdose of magnesium sulphate and life
      threatening consequences. CONCLUSIONS: Appropriate administration of antenatal
      magnesium sulphate was not shown to be associated with serious maternal adverse
      effects, though an increase in 'minor' adverse effects and treatment cessation
      was shown. Larger trials are needed to determine optimal regimens, achieving
      maximal effectiveness with minimal adverse effects, for each antenatal indication
      for use. Vigilance in the use of magnesium sulphate is essential for women's
      safety.

PMID- 24139449
TI  - The author's reply.

PMID- 24139450
TI  - Stent malapposition, as a potential mechanism of very late stent thrombosis after
      bare-metal stent implantation: a case report.
AB  - A 90-year-old man was admitted to our hospital with acute ST-segment elevation
      myocardial infarction. He had a history of post-infarction angina pectoris
      79months ago and had a bare-metal stent (BMS) implanted in the proximal left
      anterior descending artery at our hospital. Emergent coronary angiography
      demonstrated thrombotic occlusion in the previously stented segment. After
      catheter thrombectomy, antegrade flow was restored, but 90% stenosis with
      haziness persisted in the proximal and distal portions of the previously stented
      segment. Intravascular ultrasound imaging showed interstrut cavities or stent
      malapposition at the proximal and distal sites of stented segment. In close
      proximity to the sites, residual thrombi were also observed. Optical coherence
      tomography (OCT) demonstrated neither lipid-laden neointimal tissue nor rupture
      but clearly demonstrated residual thrombus adjacent to the malapposed region in
      addition to the stent malapposition. PCI with balloon was successfully performed
      and stent apposition was confirmed by OCT. Stent malapposition is an unusual
      mechanism of very late stent thrombosis after BMS implantation. OCT can clearly
      reveal the etiology of stent thrombosis. 

PMID- 24139451
TI  - Adhesion molecules of detrusor muscle cells are influenced by a
      hypercholesterolemic diet or bladder outlet obstruction in a Wistar rat model.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) are essential for maintaining tissue
      integrity by regulating intercellular and cell to extracellular matrix
      interactions. Cadherins and catenins are CAMs that are located on the cell
      membrane and are important for adherens junction (AJ) function. This study aims
      to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO)
      promotes structural bladder wall modifications specific to alterations in the
      expression of cadherins and catenins in detrusor muscle cells. METHODS: Forty
      five 4-week-old female Wistar rats were divided into the following three groups:
      group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO
      model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25%
      cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were
      determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas
      group 2 underwent a partial BOO procedure that included a suture tied around the
      urethra. Six weeks later, all rats had their bladders removed, and previous exams
      were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and
      alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a
      semiquantitative analysis. RESULTS: Wistar rats fed a HCD (group 3) exhibited a
      significant increase in LDL cholesterol levels (p=0.041) and body weight
      (p=0.017) when compared to both groups that were fed a normal diet in a ten-week
      period. We found higher beta- and gamma-catenin expression in groups 2 and 3 when
      compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed
      Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p =
      0.002). CONCLUSIONS: A HCD in Wistar rats promoted, in addition to higher body
      weight gain and increased serum LDL cholesterol levels, overexpression of beta-
      and gamma-catenin in the detrusor muscle cells. Similar finding was observed in
      the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated
      rats. These findings may be associated with bladder dysfunctions that occur under
      such situations.

PMID- 24139452
TI  - Nasolabial fold lymphadenopathy secondary to fungal rhinosinusitis.

PMID- 24139453
TI  - Osteogenesis imperfecta and hearing loss--description of three case reports.
AB  - Osteogenesis imperfecta is the commonest connective tissue hereditary disease.
      Its clinical presentation has a wide spectrum of characteristics, which includes
      skeletal deformities and hearing loss. We describe three case reports of
      individuals carriers of this disease presenting with different patterns of
      hearing loss. Hearing loss prevalence and patterns are variable and have no clear
      relation with genotype. Its assessment at initial evaluation and posterior
      monitoring is essential to provide the best therapeutic alternatives. 

PMID- 24139454
TI  - Community social capital and suicide mortality in the Netherlands: a cross
      sectional registry-based study.
AB  - BACKGROUND: Evidence on the effect of community social capital on suicide
      mortality rates is fragmentary and inconsistent. The present study aims to
      determine whether geographic variations in suicide mortality across the
      Netherlands were associated with community social capital. METHODS: We included
      3507 neighbourhoods with 6207 suicide deaths in the period 1995-2000. For each
      neighbourhood, we measured perceived social capital using information from
      interview surveys, and we measured structural aspects of social capital using
      population registers. Associations with mortality were determined using Poisson
      regression analysis with control for confounders at individual level (age, sex,
      marital status, country of origin) and area level (area income, population
      density, religious orientation). RESULTS: Suicide mortality rates were related to
      the measure of perceived social capital. Mortality rates were 8 percent higher
      (95% confidence interval (CI): 2 to 16 percent) in areas with low capital. In
      stratified analyses, this difference was found to be significantly larger among
      men (12 percent, CI: 2 to 22) than women (1 percent, CI: -9 to 13), larger among
      those age 0-50 (18 percent, CI: 8 to 29) than older residents (-2 percent, CI: 
      12 to 8), and larger among the unmarried (30 percent, CI: 16-45) than the married
      (-2 percent, CI: -12 to 9). Associations with the structural aspect of social
      capital were in the same direction, but weaker, and not statistically
      significant. CONCLUSIONS: This study contributed some evidence to assume a modest
      effect of community social capital on suicide mortality rates. This effect may be
      restricted to specific population groups such as younger unmarried men.

PMID- 24139455
TI  - Investigation on subcellular localization of Rice stripe virus in its vector
      small brown planthopper by electron microscopy.
AB  - BACKGROUND: Rice stripe virus (RSV), which is transmitted by small brown
      planthopper (Laodelphax striatellus Fallen, SBPH), has been reported to be
      epidemic and cause severe rice stripe disease in rice fields in many East Asian
      countries, including China. Investigation on viral localization in the vector is
      very important for elucidating transmission mechanisms of RSV by SBPH. In this
      study, transmission electron microscopy and immuno-gold labeling technique were
      used to investigate the subcellular localization of the ribonucleoproteins (RNPs)
      of RSV in the digestive tract, muscles, ovary and testes of SBPH. RESULTS: A lot
      of amorphous RSV inclusion bodies with high electron density were observed in the
      cytoplasmic matrix and vacuoles of follicular cells of ovarioles in viruliferous
      SBPH, which were very similar to viral inclusions formed in rice cells. After
      magnified, it was found that sand-like or parallel filamentary structures were
      constructed inside the electron-dense inclusions. A large numbers of RSV RNPs
      distributed diffusely throughout the eggshell surface and interior of ovum,
      midgut lumen and epithelial cells, while the amount of the virus in muscles was
      far less than that in the ovary and midgut tissues. Besides RSV, numerous
      endogenous microorganisms were also observed in SBPH body, including yeast-like
      endosymbiotes (YLES), endosymbiotic bacteria and insect virus. CONCLUSIONS:
      According to the results of the virus localization, a potential mechanism of RSV
      transovarial transmission was proposed that RSV might replicate and accumulate
      initially in the inclusions of follicular cells, then exploit the pathway of the
      nutrition transportation to pass through the eggshell and spread into the oocytes
      along with the nutrition. Moreover, RSV might exploit muscles for its spread in
      vector body with a lower efficiency.

PMID- 24139456
TI  - Superior vena cava drainage during thoracoscopic cardiac surgery: bilateral
      internal jugular vein sheaths versus one percutaneous superior vena cava cannula.
AB  - OBJECTIVE: To evaluate bilateral internal jugular vein sheaths as a replacement
      of one percutaneous superior vena cava cannula for superior vena cava drainage
      during thoracoscopic cardiac surgery. DESIGN: A prospective and randomized study.
      SETTING: Single cardiovascular institute. PARTICIPANTS: Adults undergoing
      thoracoscopic cardiac surgery. INTERVENTIONS: Patients were randomized into a
      percutaneous superior vena cava cannula group and a bilateral internal jugular
      vein sheaths group. The superior vena cava drainage for cardiopulmonary bypass
      was performed with one percutaneous superior vena cava cannula (14-18 Fr) or the
      bilateral internal jugular vein sheaths (8 Fr). MEASUREMENTS AND MAIN RESULTS:
      Both interventions reached theoretic flow rate in all patients. In patients
      weighing<50 kg (n=38) and 50-70 kg (n=64), the average central venous pressure
      values during cardiopulmonary bypass of both groups showed no significant
      differences. The patients weighing>70 kg (n=15) in the bilateral internal jugular
      vein sheaths group had a normal average central venous pressure value, but it was
      significantly higher than that of percutaneous superior vena cava cannula group
      ([10.5+/-3.1] mmHg vs. [4.5+/-4.4] mmHg, p=0.013). The patient satisfaction scale
      scores for the cervical incisions were significantly higher in the bilateral
      internal jugular vein sheaths group than in the percutaneous superior vena cava
      cannula group ([2.6+/-0.9] vs. [2.1+/-0.8], p=0.002). CONCLUSIONS: The bilateral
      internal jugular vein sheaths were a feasible and effective option to replace one
      percutaneous superior vena cava cannula during thoracoscopic cardiac surgery,
      with better patient satisfaction.

PMID- 24139457
TI  - The effect of preoperative beta-blocker use and race on long-term survival after
      coronary artery bypass grafting.
AB  - OBJECTIVE: To date, racial differences in the long-term survival of coronary
      artery bypass grafting (CABG) patients who receive preoperative beta-blockers
      have not been specifically examined. The purpose of this study was to examine the
      effect of preoperative beta-blockers on long-term survival among black CABG
      patients and to compare the magnitude of this effect with white patients. DESIGN:
      A retrospective cohort study. SETTING: A tertiary referral heart hospital.
      PARTICIPANTS: 13,354 patients undergoing CABG between 1992 and 2011. MEASUREMENTS
      AND MAIN RESULTS: Hazard ratios (HR) and 95% confidence intervals (CI) were
      computed using a Cox regression model. A total of 1,448 (62%) black and 6,094
      (55%) white patients had a history of preoperative beta-blocker use. Among black
      patients, those receiving beta-blockers survived longer than those not receiving
      beta-blockers (adjusted HR = 0.77, 95% CI = 0.67-0.88). The survival advantage
      was comparable to that observed among white patients (adjusted HR = 0.88, 95% CI
      = 0.82-0.93). CONCLUSION: Black CABG patients benefited from preoperative beta
      blockers and the magnitude of the effect was comparable to that among white
      patients.

PMID- 24139459
TI  - Contemporary Chinese pulse diagnosis: a modern interpretation of an ancient and
      traditional method.
AB  - Contemporary Chinese pulse diagnosisTM (CCPD) is a system of pulse diagnosis
      utilized by Dr. John He Feng Shen, OMD, and documented by Dr. Leon Hammer, MD, in
      the book Chinese Pulse Diagnosis, A Contemporary Approach. It is the traditional
      method of the Ding medical lineage from the Shanghai region and dates to the 15th
      century in Chinese language texts. The fundamentals of this system are, however,
      much older and can be directly traced to the Neijing Suwen. Having been passed
      from the last direct inheritor of Ding knowledge (Dr. Shen) to modern
      practitioners of Chinese medicine by way of Dr. Hammer and his students, it
      represents an important system of advanced diagnosis. Although modern diagnostic
      technology provides very sophisticated diagnoses, for these instruments to be
      effective, the disease process must already have a physical manifestation. CCPD,
      on the other hand, provides the earliest warnings of physiological processes,
      which if left unchecked may result in the subsequent appearance of a disease.
      This article describes the derivation and the principles of this system of pulse
      diagnosis and explores its successful integration into the modern practice of
      Chinese medicine. 

PMID- 24139460
TI  - Amygdaloid corticotropin-releasing factor is involved in the anxiolytic effect of
      acupuncture during ethanol withdrawal in rats.
AB  - In a previous study, acupuncture at acupoint HT7 attenuated ethanol withdrawal
      induced anxiety-like behavior in rats by normalizing amygdaloid catecholamines.
      In the present study, the involvement of amygdaloid corticotropin-releasing
      factor (CRF) in the anxiolytic effect of acupuncture was investigated during
      ethanol withdrawal. Rats were intraperitoneally treated with 3 g /kg/day of
      ethanol for 28 days, and the CRF mRNA levels in the central nucleus of the
      amygdala (CEA) were measured by using a RT-PCR analysis 72 hours after the last
      dose of ethanol. During ethanol withdrawal, the rats were bilaterally treated
      with acupuncture at acupoints HT7, PC6 or at a non-acupoint (Tail) for one
      min/day for three days. Also, rats were bilaterally injected with CRF into the
      CEA five minutes after the third acupuncture treatment, after which followed by
      the elevated-plus maze (EPM) test and the plasma corticosterone radioimmunoassay
      (RIA) were administered. The RT-PCR analysis showed a significant increase in the
      amygdaloid CRF mRNA levels in the ethanol-withdrawn rats compared with both the
      saline-treated rats and the rats treated with acupuncture at HT7, but neither
      acupuncture at PC6 nor acupuncture at a non-acupoint significantly inhibited the
      increased mRNA expression. The EPM test and the RIA also showed that the post
      acupuncture infusion of CRF greatly reduced the anxiolytic effect of acupuncture
      at HT7. These results suggest that during ethanol withdrawal, the anxiolytic
      effect of acupuncture may be mediated through the modulation of amydaloid CRF
      during ethanol withdrawal. 

PMID- 24139461
TI  - The effect of acupuncture on working memory and anxiety.
AB  - OBJECTIVE: The purpose of this study was to investigate whether acupuncture can
      improve memory and reduce anxiety. DESIGN, SETTING AND SUBJECTS: A two-group,
      randomized, single-blind study involving 90 undergraduate university students was
      conducted from January to December of 2011. INTERVENTIONS: Subjects completed the
      State-Trait Anxiety Inventory (STAI) form Y-1 (State Anxiety, SA) and Y-2 (Trait
      Anxiety, TA). Then, each subject lay on a treatment table for 20 minutes. The
      acupuncture group had needles inserted into select acupoints; control subjects
      did not. Subjects then completed the STAI form Y-1 again, after which they
      completed the Automated Operation Span Task (AOSPAN) - a computerized test of
      working memory. MAIN OUTCOME MEASURES: Performance on the AOSPAN and the STAI
      scores were the main measures of the outcomes. RESULTS: The acupuncture group
      scored 9.5% higher than the control group on the AOSPAN Total Correct Score
      (65.39 vs. 59.9, p=0.0134), and committed 36% fewer math errors (2.68 vs. 4.22,
      p=0.0153). Acupuncture subjects also reported lower SA after intervention than
      control subjects (26.14 vs. 29.63, p=0.0146).

PMID- 24139462
TI  - Laser acupuncture improves memory impairment in an animal model of Alzheimer's
      disease.
AB  - The burden of Alzheimer's disease is continually rising globally, especially in
      the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy
      is still very limited. Because the effect of acupuncture at HT7 can improve
      learning and memory, the beneficial effect of laser acupuncture, a noninvasive
      form of acupuncture, at HT7 on memory improvement in patients with Alzheimer's
      disease has been a focus of research. To elucidate this issue, we used AF64A, a
      cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180
      220 g. Then, the animals were treated with laser acupuncture either at HT7 or at
      a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory
      assessments were performed at 1, 7, and 14 days after AF64A administration and at
      the end of the experiment, and the changes in the malondialdehyde (MDA) level and
      in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH
      Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded.
      The results showed that laser acupuncture significantly suppressed AChE activity
      in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities,
      no reduction in MDA level in this area was observed. Therefore, laser acupuncture
      at HT7 is a potential strategy to attenuate memory impairment in patients with
      Alzheimer's disease. However, further research, especially on the toxicity of
      laser acupuncture following repetitive exposure, is essential.

PMID- 24139463
TI  - Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide
      excision repair genes to protect skin keratinocytes from ultraviolet B-induced
      reactive oxygen species and DNA damage.
AB  - In this study, we examined the antioxidative and the DNA protective potentials of
      apigenin, a flavonoid polyphenol isolated from Lycopodium clavatum, in both in
      vitro (HaCaT skin keratinocytes) and in-vivo (mice) models against UV-B
      radiation. We used DAPI staining in UV-B-irradiated HaCaT skin keratinocytes pre
      treated with and without apigenin to assess DNA damage. We also used a flow
      cytometric analysis in mice exposed to UV-B radiation with or without topical
      application of apigenin to assess, through a comet assay, chromosomal aberrations
      and quanta from reactive oxygen species (ROS) generation. Data from the stability
      curves for the Gibb's free energy determined from a melting-temperature profile
      study indicated that apigenin increased the stability of calf thymus DNA.
      Immunofluorescence studies revealed that apigenin caused a reduction in the
      number of cyclobutane pyrimidine dimers (CPDs) after 24 h, the time at which the
      nucleotide excision repair (NER) genes were activated. Thus, apigenin accelerated
      reversal of UV-B-induced CPDs through up-regulation of NER genes, removal of
      cyclobutane rings, inhibition of ROS generation, and down-regulation of NF-kappaB
      and MAPK, thereby revealing the precise mechanism of DNA repair. 

PMID- 24139464
TI  - Data analysis of 87 tic patients for 6 months' treatment in a Korean medicine
      clinic.
AB  - This study was carried out to investigate the relationship between the
      therapeutic effects of treatment for tic disorder and Korean medicine clinical
      tests, including body mass index (BMI) and heart variability rate (HRV). This
      study was not a clinical trial, but a data analysis of 87 tic patients who were
      treated for 6 months during the time period from Nov. 2010 to Jan. 2012. The
      clinical evaluation of the symptoms was recorded using the Korean version of the
      Yale Global Tic Severity Scale (YGTSS). The BMI and the HRV were measured
      according to a schedule, and various kinds of statistical methods were used.
      Among the 87 patients, the number of males was 3.34 times the number of females,
      and 58 patients (66.7%) had been suffering for more than 12 months. The onset age
      of the males was significantly lower than that of the females, and males had the
      symptoms longer than females had. Also, males with a family history of tics were
      2.5 times as many as females, and their onset ages were substantially lower. At
      the first medical examinations, the average score on the YGTSS was 34.08, and it
      decreased linearly as the treatment progressed. After 4 and 6 months of
      treatment, it had decreased significantly. The YGTSS score and the period of
      suffering correlated positively. At the first visit, each HRV datum was in the
      normal range. After the 6 months' treatment, Ln (TP), Ln (LF), and Ln (HF) had
      dropped substantially in the normal range while Ln (VLF) and the LF/HF ratio had
      not changed in a meaningful way. During the treatment period, the BMI stayed
      relatively constant without any meaningful changes. 

PMID- 24139465
TI  - Proposed catalog of the neuroanatomy and the stratified anatomy for the 361
      acupuncture points of 14 channels.
AB  - BACKGROUND: In spite of the extensive research on acupuncture mechanisms, no
      comprehensive and systematic peer-reviewed reference list of the stratified
      anatomical and the neuroanatomical features of all 361 acupuncture points exists.
      This study creates a reference list of the neuroanatomy and the stratified
      anatomy for each of the 361 acupuncture points on the 14 classical channels and
      for 34 extra points. METHODS: Each acupuncture point was individually assessed to
      relate the point's location to anatomical and neuroanatomical features. The
      design of the catalogue is intended to be useful for any style of acupuncture or
      Oriental medicine treatment modality. The stratified anatomy was divided into
      shallow, intermediate and deep insertion. A separate stratified anatomy was
      presented for different needle angles and directions. RESULTS: The following are
      identified for each point: additional specifications for point location, the
      stratified anatomy, motor innervation, cutaneous nerve and sensory innervation,
      dermatomes, Langer's lines, and somatotopic organization in the primary sensory
      and motor cortices. Acupuncture points for each muscle, dermatome and myotome are
      also reported. CONCLUSION: This reference list can aid clinicians, practitioners
      and researchers in furthering the understanding and accurate practice of
      acupuncture. Additional research on the anatomical variability around acupuncture
      points, the frequency of needle contact with an anatomical structure in a
      clinical setting, and conformational imaging should be done to verify this
      catalogue.

PMID- 24139466
TI  - Palmar basal cell carcinoma: an unusual site?

PMID- 24139467
TI  - Erythroderma as an initial presentation of langerhans cell histiocytosis
      involving the sinus.

PMID- 24139468
TI  - Effect of imiquimod as compared with surgery on the cancerization field in basal
      cell carcinoma.
AB  - BACKGROUND: Patients with basal cell carcinoma (BCC) have an increased risk of
      subsequent BCCs. It is possible that imiquimod might reduce this risk by acting
      on the cancerization field. OBJECTIVE: To examine the ability of imiquimod to
      reduce subsequent BCCs. METHODS: Retrospective cohort study of patients with BCC
      treated at our hospital between 2003 and 2011. The patients were divided into 2
      groups depending on whether they had been treated with surgery or with imiquimod.
      Comparing the 2 groups, we analyzed the development of new BCCs, the time that
      elapsed between first and subsequent tumors, and the site of occurrence of the
      second BCC with respect to the first one (local, same lymphatic drainage basin or
      anatomic region, or other). Survival methods were used to analyze the data.
      RESULTS: We reviewed the charts of 623 patients. Of these, 550 had been treated
      with surgery (88.3%) and 71 with imiquimod (11.4%). Overall, a second BCC
      occurred in 36.4% of patients (n=227). The rate of occurrence was 38.2% in the
      surgery group and 23.9% in the imiquimod group (P=.02). The hazard ratio for the
      occurrence of a subsequent BCC was 2.13 (95% CI, 1.28-3.53) for patients treated
      with surgery compared with those treated with imiquimod. Imiquimod reduced the
      risk of a second BCC locally, regionally, and in the lymphatic drainage area. Our
      findings are limited by the retrospective nature of our study and the small
      number of patients treated with imiquimod. CONCLUSIONS: Imiquimod may reduce the
      risk of subsequent BCC in patients treated for BCC and its effect could last for
      up to 2 years in local, regional and lymphatic cancerization fields. We believe
      that the cancerization field concept should be expanded to include not only the
      local area, but also the pertinent anatomic region and the regional lymphatic
      drainage area.

PMID- 24139469
TI  - Nodular-cystic lesions on a congenital alopecic plaque.

PMID- 24139470
TI  - Aprepitant in the treatment of refractory pruritus secondary to cutaneous T-cell
      lymphoma.

PMID- 24139471
TI  - Prognosis of the intrahepatic cholangiocarcinoma after resection: hepatitis B
      virus infection and adjuvant chemotherapy are favorable prognosis factors.
AB  - AIM: The incidence and mortality associated with intrahepatic cholangiocarcinoma
      is increasing in many countries and documentation of disease outcome is sparse.
      The present study was undertaken to investigate the prognostic factors for
      intrahepatic cholangiocarcinoma (ICC) following surgical resection. The impact of
      pre-existing HBV virus infection and adjuvant chemotherapy on the overall
      survival was also evaluated. METHODS: Clinical and pathological data were
      collected retrospectively from 81 patients undergoing surgery for ICC between
      2005 and 2011, at The Henan Province Tumor Hospital and the First Affiliated
      Hospital of Zheng Zhou University. Survival and prognosis were analyzed using the
      Kaplan-Meier method and COX regression model. RESULTS: The population included 37
      patients who were HBsAg + or anti-HBc+, 21 patients who were anti-HBs + positive
      and 18 patients who received adjuvant chemotherapy. The overall 1- and 3-year
      survival rates were 51% and 20%, respectively. The median survival was 12.2
      months. Univariate analysis identified the following prognostic factors: HBV
      virus infection or HBV vaccine prior to resection (P = 0.017); adjuvant
      chemotherapy (P = 0.001); preoperative serum CA19-9 (> 200 U/mL; P = 0.015); GGT
      (> 64 U/L; P = 0.008), ALP (> 119 U/L; P = 0.01); lymph node metastasis (P =
      0.005); radical resection (P = 0.021); intrahepatic metastasis (P = 0.015) and
      diabetes (P = 0.07). Multivariate analysis identified chronic HBV infection (RR =
      0.583; P = 0.041), anti-HBs positivity (RR = 0.680; P = 0.050), adjuvant
      chemotherapy (RR = 0.227; P < 0.001), lymph node metastasis (RR = 2.320; P =
      0.001), and intrahepatic duct stones (RR = 0.473; P = 0.032) as independent
      prognostic factors. CONCLUSIONS: HBV virus infection or HBV vaccination prior to
      resection, together with adjuvant chemotherapy, were independently associated
      with improved survival in patients undergoing surgery for ICC.

PMID- 24139472
TI  - Experience of tubo-ovarian abscess in western Turkey.
AB  - OBJECTIVE: To investigate the clinical and laboratory parameters, treatments, and
      complications of patient with tubo-ovarian abscess (TOA). METHODS: Data for 296
      patients diagnosed with TOA (clinically and sonographically) between January 2005
      and December 2012 were retrospectively reviewed at 3 tertiary referral hospitals
      in Turkey. Patients were compared on the basis of TOA size, demographic
      characteristics, clinical and sonographic presentation, and laboratory findings.
      RESULTS: Seventy-six patients (25.7%) underwent surgery because antibiotic
      treatment was unsuccessful. The mean abscess size was larger and the mean C
      reactive protein (CRP) level and the erythrocyte sedimentation rate (ESR) were
      higher among patients who required surgery. The ESR had a diagnostic value of
      83.6%, and a specificity and sensitivity of 73.7% and 82.7%, respectively, for
      the need for surgical intervention, based on a cut-off value of 63.0mm/hour. The
      CRP level had a diagnostic value of 80.4%, a specificity of 82.3%, and a
      sensitivity of 65.8% based on a cut-off value of 21.0mg/L. CONCLUSION: The
      combined use of the sonographic TOA diameter and laboratory parameters (ESR and
      CRP level) can aid clinical treatment decisions and improve the prediction of the
      outcome of medical TOA treatment.

PMID- 24139473
TI  - Management of female infertility from hormonal causes.
AB  - Hormonal causes of female infertility involve ovulatory dysfunctions that may
      result from dysfunction of the hypothalamic-pituitary-ovarian axis, peripheral
      endocrine glands, nonendocrine organs, or metabolic disorders. It is important to
      think of anovulation not as a diagnosis but as a symptom of a metabolic or
      endocrine disorder that requires a thorough diagnostic evaluation to identify the
      specific cause and to implement effective therapies that assure the best possible
      pregnancy outcome and avoid long-term adverse health consequences. In most
      instances, the medical history points to the underlying dysfunction, which can
      usually be confirmed with laboratory or imaging tests. For more challenging
      cases, more extensive evaluations may be needed, including perturbation studies.
      Nevertheless, the management of anovulatory infertility is gratifying because its
      causes are often manifest and the treatment usually results in resumption of
      ovulatory cycles, restoration of fertility, and healthy offspring through natural
      conception without requiring expensive and intrusive assisted reproductive
      technologies. 

PMID- 24139474
TI  - Factors affecting compliance in the first year of postcolposcopy surveillance
      among women with a high incidence of cervical cancer.
AB  - OBJECTIVE: To assess postcolposcopy compliance among women with abnormal cervical
      screening results and to identify factors associated with noncompliance for
      postcolposcopy follow-up. METHODS: In a retrospective study, the records of women
      who underwent colposcopy at Srinagarind Hospital, Thailand, between January and
      December 2010 were reviewed. Women were considered to be noncompliant if their
      total follow-up time after colposcopy was less than 12months. Univariate and
      multivariate logistic regression methods were used to determine factors
      significantly predicting noncompliance. RESULTS: Among 548 women who underwent
      colposcopy, the percentage of noncompliance was 49.5% (95% confidence interval
      [CI], 45.1%-53.7%). The risk for noncompliance rose significantly among those
      without intraepithelial lesions (OR, 2.19; 95% CI, 1.53-3.13), younger age (OR,
      1.79; 95% CI, 1.19-2.67), and low education level (OR, 1.58; 95% CI, 1.11-2.24).
      Risk for noncompliance was significantly lower among those with a previous
      history of abnormal smear (OR, 0.39; 95% CI, 0.24-0.64). CONCLUSION: The
      percentage of noncompliance with postcolposcopy follow-up was high among the
      study women. The significant independent factors predicting noncompliance were
      previous history of abnormal smear, severity of cervical histopathology, age, and
      education level.

PMID- 24139475
TI  - Construction of novel cytokine by fusion of chicken IL-2 signal peptide to mature
      chicken IL-15 and comparison of the adjuvant effects by DNA immunization against
      Eimeria challenge.
AB  - A novel fusion cytokine was constructed by replacing signal peptide (SP) of
      chicken IL-15 (ChIL-15) with SP of chicken IL-2 (ChIL-2). The fusion cytokine
      (NChIL-15) was cloned into the expression vector pcDNA3.1(+) to generate pcDNA
      NChIL-15. An animal experiment was carried out to evaluate the adjuvant effects
      of NChIL-15 on DNA vaccine pcDNA-3-1E against Eimeria acervulina challenge. The
      mRNA profiles of ChIL-2 and ChIFN-gamma in spleen were characterized by means of
      real-time PCR. The recombinant positive eukaryotic expression plasmid pcDNA-NChIL
      15 were constructed successfully. The protective effects provided by co
      immunization with 100 MUg pcDNA-3-1E and 50 MUg pcDNA-NChIL-15, measured by
      relative body weight gain (BWG), average lesion score in duodenum and oocyst
      decrease ratio, showed no significant difference with 50 MUg pcDNA-ChIL-15 as an
      adjuvant on day 6 post infection (PI). However, chickens co-immunized with pcDNA
      3-1E and pcDNA-NChIL-15 exhibited significant upregulated level of ChIL-2 and
      ChIFN-gamma transcripts in spleen. Our original data suggests the constructed
      novel cytokine NChIL-15 could be a potential adjuvant used to enhance the immune
      protective effects, although the optimized dosage need to be explored further.

PMID- 24139476
TI  - Persistence of measles neutralizing antibody related to vaccine and natural
      infection acquired before HIV infection.
AB  - Little is known about long-lasting measles protective immunity when exposure to
      wild-type or vaccine measles virus precedes HIV infection. The results obtained
      suggest that measles immunity wanes and the lowest measles geometric mean titres
      (GMT) were significantly associated with measles vaccine-induced immunity in
      individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml)
      compared to naturally induced immunity in HIV-infected adults (100% prevalence,
      GMT 340 mIU/ml, P = 0.0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P =
      0.0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347
      mIU/ml, P = 0.017). The study was conducted in an area without wild-type virus
      circulation since 2000. The absence of virus circulating may alter the paradigm
      of lifelong immunity to measles virus after vaccination. As the proportion of HIV
      infected individuals possessing only vaccine-induced immunity continues to grow,
      checking the status of measles immunity in this group is strongly recommended.

PMID- 24139477
TI  - Dyspepsia among patients with chronic kidney disease: a cross sectional study.
AB  - BACKGROUNDS: Dyspepsia is a condition that affects 25% of the U.S. population,
      and, when associated with pyrosis, its prevalence reaches 40%. Patients with
      chronic renal insufficiency not only present higher circulating levels of gastrin
      and gastric dysmotilty, but also make use of a great amount of drugs for the
      treatment of their comorbidities. This situation increases the chances of
      developing gastrointestinal symptoms. The aim of the current study is to evaluate
      the dyspeptic disease profile in patients undergoing hemodialysis, comparing them
      with chronic renal disease patients in conservative treatment and non-renal
      injury patients. METHODS: This is a cross sectional study performed at the
      Gastroenterology department at Faculdade de Medicina do ABC in Sao Paulo, Brazil.
      Three groups were set aside according to the renal function levels calculated
      using the simplified MDRD formula. They answered three questionnaires that
      evaluated the presence of dyspepsia, functional dyspepsia and gastroesophageal
      reflux disease (GERD) associated with the performance of high digestive
      endoscopy. RESULTS: A significant difference between the groups was observed
      concerning the renal function evaluated by the rates of creatinine clearance,
      creatinine and urea (p < 0.001). The rate of dyspepsia in the control group was
      higher than in patients with renal function alterations (p = 0.014). There was no
      difference between groups when it came to the presence of functional dyspepsia
      and GERD. However, there was a higher use of proton pump inhibitors in the
      hemodialysis group than in the other groups (p < 0.001). CONCLUSION: In the
      proposed model, there was no positive correlation between the worsening of the
      renal function and the presence of dyspepsia, functional dyspepsia and GERD. The
      longitudinal evaluation of hemodialysis patients is hampered by the high
      mortality rates in this group. There was a higher use of proton pump inhibitors,
      and it is believed that the dyspeptic symptoms are not acid-related.

PMID- 24139478
TI  - A critique of evidence for human occupation of Europe older than the Jaramillo
      subchron (~1 Ma): comment on 'The oldest human fossil in Europe from Orce
      (Spain)' by Toro-Moyano et al. (2013).

PMID- 24139479
TI  - Rapidly progressing primary splenic angiosarcoma with fatal hemorrhagic event.
AB  - Primary angiosarcoma of the spleen is an extremely rare malignancy. Splenic
      angiosarcoma is difficult to diagnose, and treatment is often challenging. The
      prognosis is dismal, with a mean survival of less than 1 year. Currently, no
      standard treatment methods have been established. Anecdotal reports suggest that
      early diagnosis and prompt splenectomy followed by cytotoxic chemotherapy can be
      effective treatment modalities. We report a case of rapidly progressing primary
      splenic angiosarcoma with multiple liver and bone metastases and a fatal
      hemorrhagic outcome. 

PMID- 24139480
TI  - Response to the letter from Marc B Stone, MD; Tarek A Hammad, MD, PhD, MSc, MS.

PMID- 24139481
TI  - Prevalence of porcine cysticercosis and associated risk factors in smallholder
      pig production systems in Mbeya region, southern highlands of Tanzania.
AB  - Porcine cysticercosis (PC) caused by the larval stage of a zoonotic tapeworm
      Taenia solium, is known to pose serious economic losses and public health risk
      among smallholder pig production communities. The present study was conducted to
      determine prevalence and associated risk factors for PC in smallholder pig
      production systems in Mbeya region, the major pig rearing region of Tanzania. A
      cross-sectional survey employing a random sample of 300 pig keepers from 30
      villages of Mbozi and Mbeya Rural districts, Mbeya region were used to evaluate
      pig production systems and practices. Concurrently, 600 male and female pigs of
      different age categories were randomly selected and examined for PC using lingual
      examination method and antigen enzyme-linked immunosorbent assay (Ag-ELISA). The
      overall pig level PC prevalence in Mbozi district was 11.7% (95% CI=8.5-15.8%)
      and 32% (95% CI: 27-37.5%) based on lingual examination and Ag-ELISA,
      respectively. In Mbeya Rural district, the prevalences were 6% (95% CI: 3.8-9.3%)
      and 30.7% (95% CI: 25.8-36.1%) by lingual examination and Ag-ELISA, respectively.
      In Mbozi district 46% of the households were found infected (one or more infected
      pigs) and the corresponding figure was 45% for Mbeya Rural district. The
      agreement between lingual examination and Ag-ELISA was poor (kappa<0.40). There
      were no significant differences in the prevalence of PC in different sex
      categories of pigs. Significant risk factors associated with PC prevalence were
      free roaming of pigs (OR=2.1; 95% CI=1.3-3.6; p=0.006), past experience of
      porcine cysticercosis in the household (OR=2.6; 95% CI=1.5-4.8; p=0.002),
      increased age of pig (OR=1.9; 95% CI=1.2-3.0), slatted raised floor in pig pen
      (OR=8.4; 95% CI=1.0-70.0), in-house origin of the pig (OR=1.6; 95% CI=1.1-2.5)
      and sourcing of water from rivers (OR=3.1; 95% CI=1.6-6.3; p<0.001) and ponds
      (OR=5.0; 95% CI=1.2-21.7; p=0.031). This study has clearly revealed a high sero
      prevalence of PC in the study area, which imposes a major economical and public
      health burden to the smallholder pig farmers. The study also points to a number
      of important risk factors in smallholder pig management that may be addressed
      (e.g. confinement, quality of pens and water sources) in future interventions and
      educational campaigns for control of T. solium.

PMID- 24139482
TI  - Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate
      serine recombinases for the integration of DNA into the human genome.
AB  - BACKGROUND: Phage-encoded serine integrases, such as phiC31 integrase, are widely
      used for genome engineering. Fifteen such integrases have been described but
      their utility for genome engineering has not been compared in uniform assays.
      RESULTS: We have compared fifteen serine integrases for their utility for DNA
      manipulations in mammalian cells after first demonstrating that all were
      functional in E. coli. Chromosomal recombination reporters were used to show that
      seven integrases were active on chromosomally integrated DNA in human fibroblasts
      and mouse embryonic stem cells. Five of the remaining eight enzymes were active
      on extra-chromosomal substrates thereby demonstrating that the ability to mediate
      extra-chromosomal recombination is no guide to ability to mediate site-specific
      recombination on integrated DNA. All the integrases that were active on
      integrated DNA also promoted DNA integration reactions that were not mediated
      through conservative site-specific recombination or damaged the recombination
      sites but the extent of these aberrant reactions varied over at least an order of
      magnitude. Bxb1 integrase yielded approximately two-fold more recombinants and
      displayed about two fold less damage to the recombination sites than the next
      best recombinase; phiC31 integrase. CONCLUSIONS: We conclude that the Bxb1 and
      phiC31 integrases are the reagents of choice for genome engineering in vertebrate
      cells and that DNA damage repair is a major limitation upon the utility of this
      class of site-specific recombinase.

PMID- 24139483
TI  - Metal block augmentation for bone defects of the medial tibia during primary
      total knee arthroplasty.
AB  - BACKGROUND: Stable and well-aligned placement of tibial components during primary
      total knee arthroplasty is challenging in patients with bone defects. Although
      rectangular block-shaped augmentations are widely used to reduce the shearing
      force between the tibial tray and bone compared with wedge-shaped augmentations,
      the clinical result remains unclear. This study aimed to evaluate the outcome of
      primary total knee arthroplasty with metal block augmentation. METHODS: We
      retrospectively reviewed the 3- to 6-year follow-up results of 33 knees that
      underwent total knee arthroplasty with metal block augmentation (metal-augmented
      group) for bone defects of the medial tibia and 132 varus knees without bone
      defects as the control group. All surgeries were performed using posterior
      stabilized cemented prostheses in both groups. Cemented stems were routinely
      augmented when the metal block was used. RESULTS: There were no differences in
      implant survival rates (100% in metal-augmented and 99.2% in control) or knee
      function scores (82 points in metal-augmented and 84 points in control) between
      the two groups at the final follow-up examination (P = 0.60 and P = 0.09,
      respectively). No subsidence or loosening of the tibial tray was observed. Of 33
      metal-augmented total knee arthroplasties, a nonprogressive radiolucent line
      beneath the metal was detected in 10 knees (30.3%), and rounding of the medial
      edge of the tibia was observed in 17 knees (51.5%). CONCLUSIONS: The clinical
      results of total knee arthroplasty with metal augmentation were not inferior to
      those in patients without bone defects. However, radiolucent lines were observed
      in 30.3%.

PMID- 24139484
TI  - Novel omega-conotoxins from C. catus reverse signs of mouse inflammatory pain
      after systemic administration.
AB  - BACKGROUND: Antagonists of N-type voltage-gated calcium channels (VGCC),
      Ca(v)2.2, can manage severe chronic pain with intrathecal use and may be
      effective systemically. A series of novel omega-conotoxins that selectively
      inhibit N-type VGCCs was isolated from Conus catus. In the present study, the
      potency and reversibility of omega-conotoxins CVID, CVIE and CVIF to inhibit N
      type calcium currents were investigated in mouse isolated dorsal root ganglion
      (DRG) neurons. The systemic potency of each omega-conotoxin to reverse signs of
      mouse chronic inflammatory pain was also compared. RESULTS: In DRG neurons, the
      rank order of potency to inhibit N-type calcium currents was CVIE > CVIF > CVID.
      After subcutaneous administration, CVID and CVIE, but not CVIF, partially
      reversed impaired weight bearing in mice injected with Freund's complete adjuvant
      (CFA) three days prior to testing. No side-effects associated with systemic
      administration of omega-conotoxins were observed. CONCLUSIONS: The present study
      indicates a potential for CVID and CVIE to be developed as systemically active
      analgesics with no accompanying neurological side-effects.

PMID- 24139485
TI  - Community food program use in Inuvik, Northwest Territories.
AB  - BACKGROUND: Community food programs (CFPs) provide an important safety-net for
      highly food insecure community members in the larger settlements of the Canadian
      Arctic. This study identifies who is using CFPs and why, drawing upon a case
      study from Inuvik, Northwest Territories. This work is compared with a similar
      study from Iqaluit, Nunavut, allowing the development of an Arctic-wide
      understanding of CFP use - a neglected topic in the northern food security
      literature. METHODS: Photovoice workshops (n=7), a modified USDA food security
      survey and open ended interviews with CFP users (n=54) in Inuvik. RESULTS: Users
      of CFPs in Inuvik are more likely to be housing insecure, female, middle aged (35
      64), unemployed, Aboriginal, and lack a high school education. Participants are
      primarily chronic users, and depend on CFPs for regular food access. CONCLUSIONS:
      This work indicates the presence of chronically food insecure groups who have not
      benefited from the economic development and job opportunities offered in larger
      regional centers of the Canadian Arctic, and for whom traditional kinship-based
      food sharing networks have been unable to fully meet their dietary needs. While
      CFPs do not address the underlying causes of food insecurity, they provide an
      important service for communities undergoing rapid change, and need greater focus
      in food policy herein.

PMID- 24139486
TI  - Bayesian optimization of time perception.
AB  - Precise timing is crucial to decision-making and behavioral control, yet
      subjective time can be easily distorted by various temporal contexts. Application
      of a Bayesian framework to various forms of contextual calibration reveals that,
      contrary to popular belief, contextual biases in timing help to optimize overall
      performance under noisy conditions. Here, we review recent progress in
      understanding these forms of temporal calibration, and integrate a Bayesian
      framework with information-processing models of timing. We show that the
      essential components of a Bayesian framework are closely related to the clock,
      memory, and decision stages used by these models, and that such an integrated
      framework offers a new perspective on distortions in timing and time perception
      that are otherwise difficult to explain. 

PMID- 24139487
TI  - Evaluation of trypanocidal drugs used for human African trypanosomosis against
      Trypanosoma lewisi.
AB  - Trypanosomes from animals are potential pathogens for humans. Several human cases
      infected by Trypanosoma lewisi, a parasite of rats, have been reported. The
      number of these infections is possibly underestimated. Some infections were self
      cured, others required treatment with drugs used in human African trypanosomosis.
      An in vitro evaluation of these drugs and fexinidazole, a new oral drug
      candidate, has been performed against T. lewisi in comparison with T. brucei
      gambiense. All have comparable activities against the two parasites. Suramin was
      not effective. In vivo, drugs were tested in rats immunosuppressed by
      cyclophosphamide. The best efficacy was obtained for fexinidazole, and
      pentamidine (15 mg/kg): rats were cured in 7 and 10 days respectively. Rats
      receiving nifurtimox-eflornithine combination therapy (NECT) or pentamidine (4
      mg/kg) were cured after 28 days, while melarsoprol was weakly active. The
      identification of efficient drugs with reduced toxicity will help in the
      management of new cases of atypical trypanosomosis.

PMID- 24139489
TI  - Medical care in outer space: a useful paradigm for underserved regions on the
      planet.

PMID- 24139488
TI  - Mixed adeno(neuro)endocrine carcinoma arising from the ectopic gastric mucosa of
      the upper thoracic esophagus.
AB  - We report a case of mixed adenoendocrine carcinoma of the upper thoracic
      esophagus arising from ectopic gastric mucosa. A 64-year-old man who had been
      diagnosed with an esophageal tumor on the basis of esophagoscopy was referred to
      our hospital. Upper gastrointestinal endoscopy revealed the presence of ectopic
      gastric mucosa and an adjacent pedunculated lesion located on the posterior wall
      of the upper thoracic esophagus. Subtotal esophagectomy with three-field lymph
      node dissection was performed. A microscopic examination revealed that there was
      a partially intermingling component of neuroendocrine carcinoma adjacent to a
      tubular adenocarcinoma which was conterminous with the area of the ectopic
      gastric mucosa. Although the tubular adenocarcinoma was confined to the mucosa
      and submucosa, the neuroendocrine carcinoma had invaded the submucosaand there
      was vascular permeation. Each component accounted for 30% or more of the tumor,
      so the final histopathological diagnosis was mixed adenoendocrine carcinoma of
      the upper thoracic esophagus arising from ectopic gastric mucosa. Adjuvant
      chemotherapy was not performed, because the postoperative tumor stage was IA. The
      patient was well and had no evidence of recurrence 16 months after surgery. 

PMID- 24139490
TI  - The protective role of MnTBAP in oxidant-mediated injury and inflammation in a
      rat model of lung contusion.
AB  - BACKGROUND: Lung contusion (LC) is a unique direct and focal insult that is
      considered a major risk factor for the initiation of acute lung injury and acute
      respiratory distress syndrome. We have shown recently that consumption of nitric
      oxide (due to excess superoxide) resulting in peroxynitrite formation leads to
      decreased vascular reactivity after LC. In this study, we set out to determine
      whether the superoxide scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin
      chloride (MnTBAP) plays a protective role in alleviating acute inflammatory
      response and injury in LC. METHODS: Nonlethal, closed-chest, bilateral LC was
      induced in a rodent model. Administration of the superoxide dismutase mimetic
      MnTBAP concurrently in LC in rats was performed, and bronchoalveolar lavage (BAL)
      and lung samples were analyzed for degree of injury and inflammation at 5 and 24
      h after the insult. The extent of injury was assessed by the measurement of cells
      and albumin with cytokine levels in the BAL and lungs. Lung samples were
      subjected to H&E and superoxide staining with dihydro-ethidium. Protein-bound
      dityrosine and nitrotyrosine levels were quantified in lung tissue by tandem mass
      spectrometry. RESULTS: The degrees of lung injury after LC as determined by BAL
      albumin levels were significantly decreased in the MnTBAP-administered rats at
      all the time points when compared to the corresponding controls. The release of
      proinflammatory cytokines and BAL neutrophils was significantly less in the rats
      administered MnTBAP after LC. Administration of MnTBAP decreased tissue damage
      and decreased necrosis and neutrophil-rich exudate at the 24-h time point.
      Staining for superoxide anions showed significantly greater intensity in the lung
      samples from the LC group compared to the LC+ MnTBAP group. High-performance
      liquid chromatography/tandem mass spectrometry revealed that MnTBAP treatment
      significantly attenuated dityrosine and nitrotyrosine levels, consistent with
      decreased oxidant injury. CONCLUSION: Superoxide dismutase mimetic-MnTBAP reduced
      permeability and oxidative injury in LC and may have a therapeutic role in
      diminishing inflammation in LC.

PMID- 24139491
TI  - Transhepatic anterior approach to the inferior vena cava in large retroperitoneal
      tumors resected en bloc with the right liver lobe.
AB  - BACKGROUND: The operative approach to large retrohepatic tumors can be
      challenging because of the difficulty in exposing the inferior vena cava (IVC)
      and controlling bleeding. The anterior approach to the IVC associated with the
      hanging maneuver for liver transection, originally described in large hepatic
      tumors, may also facilitate removal of large masses set behind the liver.
      METHODS: A prospective cohort of 10 patients with large retrohepatic tumors
      involving the IVC was selected according to restrictive criteria (ie, single low
      grade tumor, sufficient liver remnant, normal hepatic function, absence of
      cholestasis, and symptoms secondary to lower vena cava obstruction). In all
      cases, the anterior approach and the hanging maneuver were applied intentionally
      to expose the IVC without any liver mobilization. Depending on tumor
      invasiveness, either IVC-preserving (n = 7) or IVC-removing (n = 3) strategies
      were applied. Our aim was to assess the safety of the technique and the possible
      benefits for patient outcome. RESULTS: The cohort represented less than 1% of a
      series of 1,168 major hepatectomies performed in our unit between 2005 and 2011.
      The median age of the patients was 58; adrenal tumors and retroperitoneal
      sarcomas accounted for 70% of the series. Total vascular liver exclusion was
      necessary in 3 patients. Median operative time was 420 min. R0 resection was
      obtained in all cases, with no mortality and 40% overall morbidity. Overall
      survival was 83% at 5 years. CONCLUSION: The transhepatic, anterior approach to
      the IVC is a safe procedure that improves vascular control, facilitates vein
      repair or reconstruction, and allows potentially curative resection of large
      retrohepatic tumors. This approach should be the preferred choice to be adopted
      in properly selected patients.

PMID- 24139492
TI  - Facilitators and challenges to implement the American College of
      Surgeons/Association of Program Directors in Surgery National Surgical Skills
      Curriculum in the European Union.

PMID- 24139493
TI  - Severe systemic vasospasm causing recurrent cardiac arrest after orthotopic heart
      transplantation.

PMID- 24139494
TI  - Capsaicin treatment reduces nasal hyperreactivity and transient receptor
      potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in
      patients with idiopathic rhinitis.
AB  - BACKGROUND: Idiopathic rhinitis (IR) is a prevalent condition for which capsaicin
      nasal spray is the most effective treatment. However, the mechanisms underlying
      IR and the therapeutic action of capsaicin remain unknown. OBJECTIVE: We sought
      to investigate the molecular and cellular bases of IR and the therapeutic action
      of capsaicin. METHODS: Fourteen patients with IR and 12 healthy control subjects
      (HCs) were treated with intranasal capsaicin. The therapeutic effect was assessed
      in patients with IR by using visual analog scale and therapeutic response
      evaluation scores, and nasal hyperreactivity was evaluated by means of cold dry
      air provocation. Nasal samples served to measure the levels of neuromediators and
      expression of chemosensory cation channels, protein gene product 9.5 (PGP 9.5),
      and the mast cell marker c-kit. The effects of capsaicin were also tested in
      vitro on human nasal epithelial cells and mast cells. RESULTS: Patients with IR
      had higher baseline transient receptor potential cation channel subfamily V,
      receptor 1 (TRPV1) expression in the nasal mucosa and higher concentrations of
      substance P (SP) in nasal secretions than HCs. Symptomatic relief was observed in
      11 of 14 patients with IR after capsaicin treatment. Expression of TRPV1;
      transient receptor potential cation channel subfamily M, receptor 8 (TRPM8); and
      PGP 9.5 was only reduced in patients with IR after capsaicin treatment. Capsaicin
      did not alter c-KIT expression or nasal epithelial morphology in patients with IR
      and HCs nor did it induce apoptosis or necrosis in cultured human nasal
      epithelial cells and mast cells. CONCLUSION: IR features an overexpression of
      TRPV1 in the nasal mucosa and increased SP levels in nasal secretions. Capsaicin
      exerts its therapeutic action by ablating the TRPV1-SP nociceptive signaling
      pathway in the nasal mucosa.

PMID- 24139495
TI  - New childhood and adult reference intervals for total IgE.

PMID- 24139496
TI  - Targeted next-generation sequencing: a novel diagnostic tool for primary
      immunodeficiencies.
AB  - BACKGROUND: Primary immunodeficiency (PID) disorders are a heterogeneous group of
      inherited disorders caused by a variety of monogenetic immune defects. Thus far,
      mutations in more than 170 different genes causing PIDs have been described. A
      clear genotype-phenotype correlation is often not available, which makes a
      genetic diagnosis in patients with PIDs complex and laborious. OBJECTIVE: We
      sought to develop a robust, time-effective, and cost-effective diagnostic method
      to facilitate a genetic diagnosis in any of 170 known PID-related genes by using
      next-generation sequencing (NGS). METHODS: We used both targeted array-based and
      in-solution enrichment combined with a SOLiD sequencing platform and a
      bioinformatic pipeline developed in house to analyze genetic changes in the DNA
      of 41 patients with PIDs with known mutations and 26 patients with undiagnosed
      PIDs. RESULTS: This novel NGS-based method accurately detected point mutations
      (sensitivity and specificity >99% in covered regions) and exonic deletions (100%
      sensitivity and specificity). For the 170 genes of interest, the DNA coverage was
      greater than 20* in 90% to 95%. Nine PID-related genes proved not eligible for
      evaluation by using this NGS-based method because of inadequate coverage. The NGS
      method allowed us to make a genetic diagnosis in 4 of 26 patients who lacked a
      genetic diagnosis despite routine functional and genetic testing. Three of these
      patients proved to have an atypical presentation of previously described PIDs.
      CONCLUSION: This novel NGS tool facilitates accurate simultaneous detection of
      mutations in 161 of 170 known PID-related genes. In addition, these analyses will
      generate more insight into genotype-phenotype correlations for the different PID
      disorders.

PMID- 24139497
TI  - Childhood asthma clusters and response to therapy in clinical trials.
AB  - BACKGROUND: Childhood asthma clusters, or subclasses, have been developed by
      computational methods without evaluation of clinical utility. OBJECTIVE: To
      replicate and determine whether childhood asthma clusters previously identified
      computationally in the Severe Asthma Research Program (SARP) are associated with
      treatment responses in Childhood Asthma Research and Education (CARE) Network
      clinical trials. METHODS: A cluster assignment model was determined by using SARP
      participant data. A total of 611 participants 6 to 18 years old from 3 CARE
      trials were assigned to SARP pediatric clusters. Primary and secondary outcomes
      were analyzed by cluster in each trial. RESULTS: CARE participants were assigned
      to SARP clusters with high accuracy. Baseline characteristics were similar
      between SARP and CARE children of the same cluster. Treatment response in CARE
      trials was generally similar across clusters. However, with the caveat of a
      smaller sample size, children in the early-onset/severe-lung function cluster had
      best response with fluticasone/salmeterol (64% vs 23% 2.5* fluticasone and 13%
      fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses
      trial; P = .011) and children in the early-onset/comorbidity cluster had the
      least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the
      Characterizing Response to Leukotriene Receptor Antagonist and Inhaled
      Corticosteroid trial). CONCLUSIONS: In this study, we replicated SARP pediatric
      asthma clusters by using a separate, large clinical trials network. Early
      onset/severe-lung function and early-onset/comorbidity clusters were associated
      with differential and limited response to therapy, respectively. Further
      prospective study of therapeutic response by cluster could provide new insights
      into childhood asthma treatment.

PMID- 24139499
TI  - Natural regulatory T cells in isolated early responders compared with dual
      responders with allergic asthma.
AB  - BACKGROUND: Natural regulatory T (Treg) cells are implicated in the regulation of
      the inflammatory response in patients with allergic asthma. OBJECTIVES: We sought
      to determine changes in Treg cell numbers in the airways and peripheral blood of
      isolated early responder (IER) versus dual responder (DR) subjects with mild
      allergic asthma before and after allergen challenge. METHODS: Induced sputum was
      collected from 22 subjects with allergic asthma (10 IERs and 12 DRs) and
      peripheral blood collected from 8 DRs with allergic asthma at 0, 7, and 24 hours
      after allergen challenge. Treg cells were identified by using fluorescently
      labeled antibodies to CD4 and forkhead box protein 3 and enumerated by using flow
      cytometry. RESULTS: There was a significant increase in the percentage of sputum
      CD4(+) cells 24 hours after allergen challenge in both IERs and DRs. The
      percentage of sputum Treg cells significantly decreased 24 hours after challenge
      in DRs but not IERs. This change was significantly correlated with the magnitude
      of the late asthmatic response. There was also a significant increase in the
      absolute number of sputum CD4(+) cells and Treg cells at 24 hours in DRs only.
      The ratio of the number of Treg cells to CD4(+) cells at 24 hours was
      significantly smaller in DRs compared with that in IERs. None of the above
      changes were observed in peripheral blood. CONCLUSIONS: DRs exhibit a diminished
      percentage of airway Treg cells after allergen challenge that is not observed in
      IERs and a significantly lower ratio of Treg cells to CD4(+) cells, which might
      contribute to the development of the late asthmatic response.

PMID- 24139500
TI  - Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in
      vitro and inhibits tumor growth in a mouse model.
AB  - BACKGROUND: Dipyrithione (PTS2) is widely used as a bactericide and fungicide.
      Here, we investigated whether PTS2 has broad-spectrum antitumor activity by
      studying its cytotoxicity and proapoptotic effects in four cancer cell lines.
      METHODS: We used MTT assays and trypan blue staining to test the viability of
      cancer cell lines. Hoechst 33258 and DAPI staining were used to observe cell
      apoptosis. Cell-cycle percentages were analyzed by flow cytometry. Apoptosis was
      assayed using caspase-3 and poly (ADP-ribose) polymerase (PARP) combined with
      Western blotting. Student's t-test was used for statistical analysis. RESULTS:
      PTS2 inhibited proliferation in four cancer cell lines in a dose-dependent
      manner. Treated cells showed shrinkage, irregular fragments, condensed and
      dispersed blue fluorescent particles compared with control cells. PTS2 induced
      cycle-arrest and death. Cleavage of caspase-9, caspase-3, and PARP were detected
      in PTS2-treated cells. Antitumor activity of PTS2 was more effective against
      widely used cancer drugs and its precursor. CONCLUSIONS: PTS2 appears to have
      novel cytotoxicity and potent broad-spectrum antitumor activity, which suggests
      its potential as the basis of an anticancer drug.

PMID- 24139501
TI  - [Glycosylation of autoantibodies in autoimmunes diseases].
AB  - Protein glycosylation is one of the most common post-translational modifications,
      involved in the well described protein biosynthesis process. Protein
      glycosylation seems to play a major role in the pathogenesis of auto-immune
      diseases. Herein are described the main alterations of autoantibody glycosylation
      associated with autoimmunes diseases such as rheumatoid arthritis, IgA
      glomerulonephritis, Schoenlein-Henoch purpura, Sjogren's syndrome, systemic
      scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis
      with polyangiitis (Wegener). Molecular identification of altered immunoglobulin
      glycosylation could lead to a better understanding of the pathogenesis of those
      diseases, might allow an evaluation of their biological activity and could even
      be a new therapeutic target. 

PMID- 24139502
TI  - Evaluation between ultrahigh pressure liquid chromatography and high-performance
      liquid chromatography analytical methods for characterizing natural dyestuffs.
AB  - An evaluation was undertaken of ultrahigh pressure liquid chromatography (UHPLC)
      in comparison to high-performance liquid chromatography (HPLC) for characterizing
      natural dyes in cultural heritage objects. A new UHPLC method was optimized by
      testing several analytical parameters adapted from prior UHPLC studies developed
      in diverse fields of research. Different gradient elution programs were tested on
      seven UHPLC columns with different dimensions and stationary phase compositions
      by applying several mobile phases, flow rates, temperatures, and runtimes. The
      UHPLC method successfully provided more improved data than that achieved by the
      HPLC method. Indeed, even though carminic acid has shown circa 146% higher
      resolution with HPLC, UHPLC resulted in an increase of 41-61% resolution and a
      decrease of 91-422% limit of detection, depending on the dye compound. The
      optimized method was subsequently assigned to analyse 59 natural reference
      materials, in which 85 different components were ascribed with different
      physicochemical properties, in order to create a spectral database for future
      characterization of dyes in cultural heritage objects. The majority of these
      reference samples could be successfully distinguished with one single method
      through the examination of these compounds' retention times and their spectra
      acquired with a photodiode array detector. These results demonstrate that UHPLC
      analyses are extremely valuable for the acquisition of more precise
      chromatographic information concerning natural dyes with complex mixtures of
      different and/or closely related physicochemical properties, essential for
      distinguishing similar species of plants and animals used to colour cultural
      heritage objects. 

PMID- 24139503
TI  - Development of a new column switching method for simultaneous speciation of
      selenometabolites and selenoproteins in human serum.
AB  - A method for the simultaneous speciation of selenoproteins and selenometabolites
      in human serum has been developed on the basis of in series three dimensional
      chromatography: size exclusion, affinity and anion exchange high performance
      liquid chromatography (3D/SE-AF-AEC-HPLC), using different columns of each type
      and hyphenation to inductively coupled plasma-(quadrupole) mass spectrometry (ICP
      qMS). The method allows the quantitative simultaneous analysis of selenoprotein P
      (SeP), extracellular glutathione peroxidase (eGPx), selenoalbumin (SeAlb),
      selenite and selenate in human serum using species-unspecific isotope dilution
      (SUID). The 3D chromatographic separation is proposed to remove typical spectral
      interferences in this matrix from chloride and bromide on (77)Se ((40)Ar(37)Cl),
      (80)Se ((79)Br(1)H) and (82)Se ((81)Br(1)H). In addition, a previous method based
      on 2D/SE-AF-HPLC is proposed as a simple alternative when low molecular mass
      selenium species are absent in the samples. The method is robust, reliable and
      fast with typical chromatographic runtime less than 35min. Detection limits are
      in the range of 0.2-1.3ng of Seg(-1). Method accuracy for determination of total
      protein-bound to Se was assessed by analyzing an human serum reference material
      (BCR-637) certified for total Se content and method reliability checked in
      samples of human serum providing results in good agreement with the total
      selenium concentration. In addition, the application of the method to commercial
      human serum and plasma reference materials for quality control analysis,
      certified for total Se, has provided, for the first time, indicative levels of
      selenium containing proteins in these samples. 

PMID- 24139504
TI  - Searching for urine biomarkers of bladder cancer recurrence using a liquid
      chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry
      metabolomics approach.
AB  - The incidence and rate of recurrence of bladder cancer is high, particularly in
      developed countries, however current methods for diagnosis are limited to
      detecting high-grade tumours using often invasive methods. A panel of biomarkers
      to characterise tumours of different grades that could also distinguish between
      patients exhibiting the disease with first incidence or recurrence could be
      useful for bladder cancer diagnostics. In this study, potential metabolic
      biomarkers have been discovered through mass spectrometry based metabolomics of
      urine. Pre-treatment urine samples were collected from 48 patients diagnosed of
      urothelial bladder cancer. Patients were followed-up through the hospital
      pathological charts to identify whether and when the disease recurred or
      progressed. Subsequently, they were classified according to whether or not they
      suffered a tumour recurrence (recurrent or stable) as well as their risk group
      according to tumour grade and stage. Identified metabolites have been analysed in
      terms of disease characteristics (tumour stage and recurrence) and have provided
      an insight into bladder cancer progression. Using both liquid chromatography and
      capillary electrophoresis-mass spectrometry, a total of 27 metabolite features
      were highlighted as significantly different between patient groups. Some, for
      example histidine, phenylalanine, tyrosine and tryptophan have been previously
      linked with bladder cancer, however until now their connection with bladder
      cancer progression has not been previously reported. The candidate biomarkers
      revealed in this study could be useful in the clinic for diagnosis of bladder
      cancer and, through characterising the stage of the disease, could also be useful
      in prognostics. 

PMID- 24139505
TI  - Determination of egg yolk xanthophylls by isocratic high-performance liquid
      chromatography.
AB  - An isocratic HPLC method was developed for the determination of eight
      xanthophylls (lutein, capsanthin, zeaxanthin, canthaxanthin, beta-apo-8'
      carotenal, ethyl-8'-apo-beta-carotene-8'-oate, citranaxanthin and beta
      cryptoxanthin; registered as additives in poultry feeding) in egg yolks. Optimum
      separation of all-E-isomers of these xanthophylls was achieved in less than 18min
      on a ProntoSIL C30 column at 27 degrees C using acetone-methanol-0.5M
      triethylammonium acetate buffer pH 7 14:5:1 (v/v) as the mobile phase with a flow
      rate of 1mL/min using spectrophotometric detection at 450nm. Other mobile phases
      were also found suitable, including acetone-water 93:7 (v/v) and acetone-methanol
      1:4 (v/v) and the influences of column temperature on the separation and addition
      of triethylammonium acetate buffer pH 7 to the mobile phase on enhancement of the
      peak areas were evaluated. Preparation of test solution from yolks included a
      short vortexing of 0.5g of yolk in 10mL of acetone, followed by 15min magnetic
      stirring under nitrogen and centrifugation. The method was validated for 5
      analytes. The calibration range was between 0.04 and 2MUg/mL and the mean
      recovery of the analytes (95%) and the intra-day precision of the method (RSD
      less than 5%) on three levels in triplicates were obtained. Analyses of eggs from
      four husbandry classes showed the presence of up to four xanthophylls (lutein,
      zeaxanthin, canthaxanthin and ethyl-8'-apo-beta-carotene-8'-oate) and traces of
      beta-cryptoxanthin. 

PMID- 24139498
TI  - Primary Immune Deficiency Treatment Consortium (PIDTC) report.
AB  - The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33
      centers in North America that study the treatment of rare and severe primary
      immunodeficiency diseases. Current protocols address the natural history of
      patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich
      syndrome, and chronic granulomatous disease through retrospective, prospective,
      and cross-sectional studies. The PIDTC additionally seeks to encourage training
      of junior investigators, establish partnerships with European and other
      International colleagues, work with patient advocacy groups to promote community
      awareness, and conduct pilot demonstration projects. Future goals include the
      conduct of prospective treatment studies to determine optimal therapies for
      primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot
      projects: newborn screening for SCID in Navajo Native Americans and B-cell
      reconstitution in patients with SCID after hematopoietic stem cell
      transplantation. Ten junior investigators have received grant awards. The PIDTC
      Annual Scientific Workshop has brought together consortium members, outside
      speakers, patient advocacy groups, and young investigators and trainees to report
      progress of the protocols and discuss common interests and goals, including new
      scientific developments and future directions of clinical research. Here we
      report the progress of the PIDTC to date, highlights of the first 2 PIDTC
      workshops, and consideration of future consortium objectives. 

PMID- 24139506
TI  - A high-throughput 2D-analytical technique to obtain single protein parameters
      from complex cell lysates for in silico process development of ion exchange
      chromatography.
AB  - The accelerating growth of the market for biopharmaceutical proteins, the market
      entry of biosimilars and the growing interest in new, more complex molecules
      constantly pose new challenges for bioseparation process development. In the
      presented work we demonstrate the application of a multidimensional, analytical
      separation approach to obtain the relevant physicochemical parameters of single
      proteins in a complex mixture for in silico chromatographic process development.
      A complete cell lysate containing a low titre target protein was first
      fractionated by multiple linear salt gradient anion exchange chromatography (AEC)
      with varying gradient length. The collected fractions were subsequently analysed
      by high-throughput capillary gel electrophoresis (HT-CGE) after being desalted
      and concentrated. From the obtained data of the 2D-separation the retention
      volumes and the concentration of the single proteins were determined. The
      retention-volumes of the single proteins were used to calculate the related
      steric-mass action model parameters. In a final evaluation experiment the
      received parameters were successfully applied to predict the retention behaviour
      of the single proteins in salt gradient AEC. 

PMID- 24139507
TI  - Age- and sex-dependent reference intervals for D-dimer: evidence for a marked
      increase by age.
AB  - INTRODUCTION: A low D-dimer is commonly used to exclude venous thromboembolism in
      low risk patients. However, the reference intervals are poorly defined and D
      dimer has been shown to increase by patient age. We aimed to establish age- and
      sex-dependent D-dimer reference intervals and to test the consequence of
      different cut-off limits. MATERIALS AND METHODS: By means of the STA-Lia test D
      dimer was measured in 1,352 subjects aged between 23 and 93years from the general
      population. A further 94 subjects were measured with the HemosIL test. RESULTS:
      The reference intervals were age-dependent with the upper 95% limit increasing
      from 0.92 FEU mg/L in the age group <50years to 2.39 FEU mg/L in the group
      >=70years. Minor differences in the reference intervals between sexes were found.
      The commonly used cut-off at 0.5 FEU mg/L resulted in a decrease of negatives
      from 91% in <50years to 56 % in >=70years. The age-dependent cut-off value
      (patient's age*0.01 FEU mg/L in 50+ years) resulted in an increase of negatives
      by age. The linear increase in D-dimer has a slope at approximately 0.0077*age,
      meaning that a cut-off at (patient's age*0.0077) FEU mg/L, gives an almost
      constant number of positives across age groups. The two assays showed a poor
      correlation and a higher percentage of positives using the STA Lia test.
      CONCLUSIONS: The age-dependent increase in D-dimer seen in patients was
      confirmed, which questions the clinical value of the present cut-off for venous
      thromboembolism.

PMID- 24139508
TI  - Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the
      prevention of recurrent venous thromboembolism: a U.S. perspective.
AB  - INTRODUCTION: Rivaroxaban is an oral direct factor Xa inhibitor that is
      noninferior to warfarin in the prevention of recurrent venous thromboembolism
      (VTE). Whether rivaroxaban is cost-effective in the prevention of recurrent VTE,
      however, is not known. MATERIAL AND METHODS: To assess the cost effectiveness of
      rivaroxaban compared with warfarin in the prevention of recurrent VTE, we built a
      Markov state-transition model over a 10-year time horizon. The base case analysis
      consisted of a hypothetical cohort of 60-year-old patients with an initial VTE
      who received secondary prophylaxis with either rivaroxaban or warfarin for 3 to
      12months. Cost estimates were derived from the Healthcare and Utilization Project
      and other sources. Probabilities were based on literature values. Outcomes
      included costs in 2011 United States dollars, quality-adjusted life-years
      (QALYs), and incremental cost effectiveness ratios (ICERs) over 10years from a
      societal perspective. RESULTS: Compared with warfarin, the rivaroxaban strategy
      cost less ($3,195 vs. $6,188) and was more effective (9.29 QALYs vs 9.14 QALYs).
      Our results were highly robust in sensitivity analyses. Warfarin was no longer
      dominated by rivaroxaban when the risk of major bleeding with rivaroxaban exceeds
      3.8% (base case estimate: 0.96%). CONCLUSION: In summary, prophylactic
      anticoagulation with rivaroxaban appears to be a cost effective, and perhaps cost
      saving, alternative to warfarin for the prevention of recurrent VTE.

PMID- 24139509
TI  - Effect of chlorpromazine on rat placenta development.
AB  - We examined the sequential histopathological changes in the placentas from rats
      exposed to chlorpromazine. Chlorpromazine was intraperitoneally administered on
      GD 14 at 50 and 100 mg/kg and the placentas were sampled on GDs 14.5, 15, 17 and
      21. The incidence of dams with complete fetal resorption was increased from GD 17
      up to 20% at 50 mg/kg and 44.4% at 100 mg/kg. The embryo/fetal weights reduced on
      GDs 15 and 17 at 50 mg/kg and during GDs 15-21 at 100 mg/kg. The placental
      weights reduced on GD 17 at 50 mg/kg and during GDs 14.5-21 at 100 mg/kg.
      Histopathologically, in the labyrinth zone, apoptotic cells were scattered in the
      trophoblastic septa without inhibition of cell proliferation on GDs 14.5 and 15
      at 50 and 100 mg/kg in a dose-dependent manner. A decrease in trophoblasts led to
      labyrinth zone hypoplasia. In the basal zone, apoptotic cells were scattered on
      GDs 14.5 and 15 at 100 mg/kg, and most of them appeared to be glycogen cells. A
      decrease in glycogen cells induced the delayed development of glycogen cell
      islands and the subsequent remaining glycogen cell islands, and led to the cystic
      degeneration of glycogen cells. In addition, failure of development of the
      glycogen cell islands led to the impaired interstitial invasion of the glycogen
      cells, and then metrial gland hypoplasia occurred.

PMID- 24139510
TI  - Magneto-responsive nanocomposites: preparation and integration of magnetic
      nanoparticles into films, capsules, and gels.
AB  - This review reports on the latest developments in the field of magnetic
      nanocomposites, with a special focus on the potentials introduced by the
      incorporation of magnetic nanoparticles into polymer and supramolecular matrices.
      The general notions and the state of the art of nanocomposite materials are
      summarized and the results reported in the literature over the last decade on
      magnetically responsive films, capsules and gels are reviewed. The most promising
      concepts that have inspired the design of magneto-responsive nanocomposites are
      illustrated through remarkable examples where the integration of magnetic
      nanoparticles into organic architectures has successfully taken to the
      development of responsive multifunctional materials. 

PMID- 24139511
TI  - The relative importance of competition and predation in environment characterized
      by resource pulses--an experimental test with a microbial community.
AB  - BACKGROUND: Resource availability and predation are believed to affect community
      dynamics and composition. Although the effects of resource availability and
      predation on prey communities are usually studied in isolation, these factors can
      also have interactive effects, especially since the outcome of competition under
      shared predation is expected to depend on resource availability. However, there
      are few experimental studies that test the interactive roles of resources and
      predation on dynamics of more complex multispecies communities. Here, we examine
      the importance of competition and predation on microbial community dynamics in a
      resource pulse environment. RESULTS: We manipulated resource availability and
      predation simultaneously in a microbial microcosm experiment, where a bacterial
      community was exposed to the protozoan predator Tetrahymena thermophila in three
      different resource concentrations (low, intermediate and high). The prey
      community consisted of three heterotrophic bacterial species: Bacillus cereus,
      Serratia marcescens and Novosphingobium capsulatum, all feeding on a shared plant
      detritus medium. In fresh culture media, all species grew in all resource
      concentrations used. However, during experiments without any addition of extra
      resources, the existing resources were soon depleted to very low levels, slowing
      growth of the three bacterial species. Prior to the microcosm experiment, we
      measured the competitive ability and grazing resistance, i.e. reduced
      vulnerability to predation, of each prey species. The three species differed in
      allocation patterns: in general, N. capsulatum had the best competitive abilities
      and B. cereus had good grazing resistance abilities. In the long-term microcosm
      experiment, N. capsulatum dominated the community without predation and, with
      predation, B. cereus was the dominant species in the intermediate and high
      resource environments. CONCLUSIONS: Short-term, single-species assays revealed
      significant differences in the allocation of competitive and defensive traits
      among the prey species. Based on these differences, we were, to some extent, able
      to predict how the long-term community structure, e.g. species dominance, is
      modified by the resource availability and predation interaction in pulsed
      resource environments. Our results are consistent with theoretical predictions
      and also highlight the importance of interactive effects of resource competition
      and predation, suggesting that these factors should not be studied in isolation.

PMID- 24139512
TI  - Pediatric parapharyngeal lesions: criteria for malignancy.
AB  - INTRODUCTION: Parapharyngeal space (PPS) pediatric lesions represent a
      heterogeneous group of uncommon neoplasms of both benign and malignant nature.
      These tumors tend to be locally advanced by the time they are diagnosed;
      consequently, an early presumptive diagnosis of malignancy is of utmost
      importance. OBJECTIVE: To highlight the occurrence of malignant PPS tumors in
      pediatric population, to determine their incidence and to describe probable
      warning clues for diagnosis. PATIENTS AND METHODS: The charts of 23 pediatric
      patients with PPS swellings were retrospectively reviewed to analyze clinical and
      pathologic data. We describe possible criteria to suspect malignancy by clinical
      and radiological examination. RESULTS: Twenty-three patients presented with
      neoplastic lesions in the PPS, benign tumors in 43.5% and malignant in 56.5%.
      Malignancy was suspected in 13 cases according to combined clinical and
      radiological criteria: a painless intraoral and neck swelling in children below
      one year old, presentation with cranial nerve palsy, nasopharyngeal mucosal or
      sub-mucosal irregular lesion, the presence of multiple lymph nodes with no
      evidence of infection, and adjacent bony skull base destruction with intracranial
      extension. CONCLUSION: Occurrence of malignancy in PPS tumors in the pediatric
      population is not uncommon. Clinicians should deliberately look for associated
      secondary signs that predict malignancy. The surgeon must understand the
      pathological spectrum of tumors of this space and the proper use of imaging
      studies to make a preoperative diagnosis. This allows for planning of a sound
      surgical approach and a proper preoperative counseling.

PMID- 24139513
TI  - Proposed use of spatial mortality assessments as part of the pesticide evaluation
      scheme for vector control.
AB  - BACKGROUND: The WHO Pesticide Evaluation Scheme to evaluate the efficacy of
      insecticides does not include the testing of a lethal effect at a distance. A
      tool was developed to evaluate the spatial mortality of an insecticide product
      against adult mosquitoes at a distance under laboratory and field conditions.
      Operational implications are discussed. METHODS: Insecticide paint, Inesfly 5A
      IGRTM, containing two organophosphates (OPs): chlorpyrifos and diazinon, and one
      insect growth regulator (IGR): pyriproxyfen, was the product tested. Laboratory
      tests were performed using "distance boxes" with surfaces treated with one layer
      of control or insecticide paint at a dose of 1 kg/6 sq m. Field tests were
      conducted up to 12 months in six experimental huts randomly allocated to control
      or one or two layers of insecticide paint at 1 kg/6 sq m. All distance tests were
      performed using reference-susceptible strains of Anopheles gambiae and Culex
      quinquefasciatus left overnight at a distance of 1 m from control or treated
      surfaces. RESULTS: After an overnight exposition at distances of 1 m, field and
      laboratory evaluations at 0 months after treatment (T0) yielded 100% mortality
      rates on surfaces treated with one layer at 1 kg/6 sq m against susceptible
      strains of An. gambiae and Cx. quinquefasciatus. Testing for long-term efficacy
      in the field gave mortality rates of 96-100% after an overnight exposition at a
      distance of 1 m for up to 12 months in huts where a larger volume was treated
      (walls and ceilings) with one or two layers of insecticide paint. CONCLUSION: A
      comprehensive evaluation of the full profile of insecticide products, both upon
      contact and spatially, may help rationalize vector control efforts more
      efficiently. Treating a large enough volume may extend a product's mortality
      efficacy in the long-term, which contact tests would fail to assess. It is hereby
      proposed to explore the development of cost effective methods to assess spatial
      mortality and to include them as one additional measurement of insecticide
      efficacy against mosquitoes and other arthropod vectors in WHOPES Phase I and
      Phase II studies.

PMID- 24139514
TI  - Pulmonary benign metastasizing leiomyoma: report of three cases.
AB  - Benign metastasizing leiomyoma is very rare and usually occurs in women who
      undergo hysterectomy and myomectomy for uterine leiomyoma. This is a benign
      spindle-shaped smooth muscle cell tumor pathologically but metastasizes to the
      extrauterine organs. Lungs are the most common site of metastasis. We observed
      three cases of pulmonary benign metastasizing leiomyoma.

PMID- 24139516
TI  - Changes in bone mineral density in uterine cervical cancer patients after
      radiation therapy.
AB  - PURPOSE: To prospectively investigate the changes in bone mineral density (BMD)
      after pelvic radiation therapy in patients with uterine cervical cancer. METHODS
      AND MATERIALS: Of 52 cervical cancer patients who received pelvic RT in our
      university hospital between 2009 and 2011, 46 patients without recurrence and who
      were followed up for more than 12 months were included in the study. The BMD of
      the irradiated region and nonirradiated regions, serum estradiol, tartrate
      resistant acid phosphatase-5b, and N-terminal cross-linking telopeptide of
      collagen 1 were measured before, at 3 months after, and at 12 months after RT.
      The patient cohort was divided into 2 groups according to estradiol level before
      RT, and the groups were defined as postmenopausal (<40 pg/mL) and premenopausal
      (>=40 pg/mL). RESULTS: The mean BMDs within the irradiation field (lumbar
      vertebra 5) in the postmenopausal and the premenopausal groups were 0.825 and
      0.910 g/cm(2) before RT and 0.746 and 0.841 g/cm(2) 12 months after RT,
      respectively. Significant decreases were observed in both groups (P<.05 and
      P<.01, respectively). In addition, in the premenopausal group the mean BMDs of
      the nonirradiated regions at thoracic vertebrae 9-12 and lumbar vertebrae 2-4
      were 0.753 and 0.958 g/cm(2) before RT and were significantly decreased to 0.706
      and 0.921 g/cm(2) 12 months after RT (P<.01 and P<.05, respectively). Estradiol
      significantly decreased 3 months after RT, whereas tartrate-resistant acid
      phosphatase-5b and N-terminal cross-linking telopeptide of collagen 1 continued
      to increase over time in the premenopausal group. CONCLUSIONS: A decrease in BMD
      in the irradiated region after RT was observed within 1 year, regardless of
      menopausal status. Furthermore, in premenopausal patients, pelvic RT caused a
      decrease in systemic BMD.

PMID- 24139517
TI  - Galectin-1 is an independent prognostic factor for local recurrence and survival
      after definitive radiation therapy for patients with squamous cell carcinoma of
      the uterine cervix.
AB  - PURPOSE: To investigate the role of galectin-1 in patients with cervical cancer
      after definitive radiation therapy. METHODS AND MATERIALS: We reviewed 154
      patients with International Federation of Gynecology and Obstetrics stage I-II
      squamous cell carcinoma. Patients underwent curative-intent radiation therapy.
      Paraffin-embedded tissues were analyzed using immunohistochemistry staining for
      galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR),
      and distant metastasis were compared among patient tissue samples with no, weak,
      and strong galectin-1 expression. The Kaplan-Meier method and the Cox
      proportional hazard model with hazard ratios and 95% confidence intervals (CIs)
      were used for univariate and multivariate analyses, respectively. RESULTS: The
      areas under the curve for the intracellular expression scores of galectin-1 for
      both LR and CSS were significantly higher than those for stromal expression.
      There were no significant differences in the demographic data, such as stage and
      serum tumor markers, between patients with and without intracellular expression
      of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard
      ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18
      3.19) (P=.010), respectively. CONCLUSION: Galectin-1 is an independent prognostic
      factor associated with LR and CSS in stage I-II cervical cancer patients
      undergoing definitive radiation therapy. Further studies targeting galectin-1 may
      improve the local control of cervical cancer.

PMID- 24139515
TI  - Interaction-based evolution: how natural selection and nonrandom mutation work
      together.
AB  - BACKGROUND: The modern evolutionary synthesis leaves unresolved some of the most
      fundamental, long-standing questions in evolutionary biology: What is the role of
      sex in evolution? How does complex adaptation evolve? How can selection operate
      effectively on genetic interactions? More recently, the molecular biology and
      genomics revolutions have raised a host of critical new questions, through
      empirical findings that the modern synthesis fails to explain: for example, the
      discovery of de novo genes; the immense constructive role of transposable
      elements in evolution; genetic variance and biochemical activity that go far
      beyond what traditional natural selection can maintain; perplexing cases of
      molecular parallelism; and more. PRESENTATION OF THE HYPOTHESIS: Here I address
      these questions from a unified perspective, by means of a new mechanistic view of
      evolution that offers a novel connection between selection on the phenotype and
      genetic evolutionary change (while relying, like the traditional theory, on
      natural selection as the only source of feedback on the fit between an organism
      and its environment). I hypothesize that the mutation that is of relevance for
      the evolution of complex adaptation-while not Lamarckian, or "directed" to
      increase fitness-is not random, but is instead the outcome of a complex and
      continually evolving biological process that combines information from multiple
      loci into one. This allows selection on a fleeting combination of interacting
      alleles at different loci to have a hereditary effect according to the
      combination's fitness. TESTING AND IMPLICATIONS OF THE HYPOTHESIS: This proposed
      mechanism addresses the problem of how beneficial genetic interactions can evolve
      under selection, and also offers an intuitive explanation for the role of sex in
      evolution, which focuses on sex as the generator of genetic combinations.
      Importantly, it also implies that genetic variation that has appeared neutral
      through the lens of traditional theory can actually experience selection on
      interactions and thus has a much greater adaptive potential than previously
      considered. Empirical evidence for the proposed mechanism from both molecular
      evolution and evolution at the organismal level is discussed, and multiple
      predictions are offered by which it may be tested. REVIEWERS: This article was
      reviewed by Nigel Goldenfeld (nominated by Eugene V. Koonin), Jurgen Brosius and
      W. Ford Doolittle.

PMID- 24139519
TI  - The determination of total burn surface area: how big is the difference?

PMID- 24139518
TI  - Transforming growth factor beta-1 (TGF-beta1) is a serum biomarker of radiation
      induced fibrosis in patients treated with intracavitary accelerated partial
      breast irradiation: preliminary results of a prospective study.
AB  - PURPOSE: To examine a relationship between serum transforming growth factor beta 
      1 (TGF-beta1) values and radiation-induced fibrosis (RIF). METHODS AND MATERIALS:
      We conducted a prospective analysis of the development of RIF in 39 women with
      American Joint Committee on Cancer stage 0-I breast cancer treated with
      lumpectomy and accelerated partial breast irradiation via intracavitary
      brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R&D,
      Minneapolis, MN) was used to measure serum TGF-beta1 before surgery, before
      IBAPBI, and during IBAPBI. Blood samples for TGF-beta1 were also collected from
      15 healthy, nontreated women (controls). The previously validated tissue
      compliance meter (TCM) was used to objectively assess RIF. RESULTS: The median
      time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was
      graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20
      patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively.
      The mean serum TGF-beta1 values were significantly higher in patients before
      surgery than in disease-free controls, as follows: all cancer patients (30,201 +/
      5889 pg/mL, P=.02); patients with any type of RIF (32,273 +/- 5016 pg/mL,
      P<.0001); and women with moderate to severe RIF (34,462 +/- 4713 pg/mL,
      P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF
      beta1 levels when compared with those with none to mild RIF before surgery
      (P=.0014) during IBAPBI (P<=0001), and the elevation persisted at 6 months
      (P<=.001), 12 months (P<=.001), 18 months (P<=.001), and 24 months (P=.12). A
      receiver operating characteristic (ROC) curve of TGF-beta1 values predicting
      moderate to severe RIF was generated with an area under the curve (AUC)ROC of
      0.867 (95% confidence interval 0.700-1.000). The TGF-beta1 threshold cutoff was
      determined to be 31,000 pg/mL, with associated sensitivity and specificity of
      77.8% and 90.0%, respectively. CONCLUSIONS: TGF-beta1 levels correlate with the
      development of moderate to severe RIF. The pre-IBAPBI mean TGF-beta1 levels can
      serve as an early biomarker for the development of moderate to severe RIF after
      IBAPBI.

PMID- 24139520
TI  - The spectrum of cardiac disease in the West Region of Cameroon: a hospital-based
      cross-sectional study.
AB  - BACKGROUND: Cardiovascular disease is a growing public health problem in Africa.
      The extent of heart disease in Cameroon remains largely unknown. This study aimed
      at reporting the etiology of cardiac disease in a cardiologic clinic situated in
      a semi-urban area in the West region of Cameroon. METHODS: This is an analysis of
      echocardiographic diagnosis of cardiac disease done between July 2008 and October
      2010 at the "Centre Medical de la Trinite" in the West region of Cameroon. Data
      included age, sex and echocardiographic findings. RESULTS: A total of 1252
      patients presented with abnormal echocardiograms, 60.4% (n = 756) being female
      and 85.8% (n = 1074) aged over 50 years. Overall, the most important conditions
      were hypertensive heart disease (41.5%, n = 520) and cardiomyopathies (30.5%, n =
      382). Among patients aged less than 10 years, congenital heart diseases were the
      most frequent (52.4%, n = 22), and rheumatic heart disease was the most important
      cardiac condition in patients aged 10 to 19 years (62.1%, n = 18) and those aged
      20 to 39 years (53.3%, n = 8). Congenital heart diseases included persistent
      ductus arteriosus (27.6%, n = 8), tetralogy of Fallot (20.7%, n = 6) and inter
      atria/interventricular communication (20.7%, n = 6). CONCLUSION: Hypertension is
      the leading cause of cardiac disease among the elderly in our setting,
      emphasizing the necessity to strengthen the preventive strategies against
      hypertension in Cameroon. Rheumatic heart disease and congenital heart disease
      frequent in children and youths highlight the need of early detection and
      treatment of throat infections, and of routine cardiac surgery services in
      Cameroon.

PMID- 24139522
TI  - The use of demineralized bone matrix for anterior cruciate ligament
      reconstruction: a radiographic, histologic, and immunohistochemical study in
      rabbits.
AB  - Tendon-bone healing is crucial in success of anterior cruciate ligament (ACL)
      reconstruction surgery. Demineralized bone matrix (DBM) is a physiological
      component that has the inherent potential of bone regeneration. We hypothesized
      that the alternative bone substitute can affect the structural properties of
      tendon graft in tibial tunnel healing. Five 12-week-old New Zealand white rabbits
      in study group underwent unilateral ACL reconstructions plus the application of
      0.5 cc DBM in the tibial tunnel. The assessment included radiological assessment
      and histologic and immunohistochemical analyses. Radiological examination
      revealed that DBM group had the least displacement of tendon in tibial tunnel
      (0.4 +/- 0.12; P = 0.03). Histologic examination showed significantly better
      integration between tendon and bone in DBM group (77.62 +/- 2.08; P = 0.001). On
      immunohistochemical analysis, the DBM group showed significantly higher
      expressions of bone morphogenetic protein-2 and vascular endothelial growth
      factor than control group (51.98 +/- 3.02, 84.06 +/- 1.86; P = 0.001, P < 0.001).
      DBM enhances the tendon-bone healing in ACL reconstruction. DBM has the potential
      use in ACL surgery. 

PMID- 24139521
TI  - KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors
      and associated implants.
AB  - BACKGROUND: Patients diagnosed for a serous ovarian borderline tumor (s-BOT)
      typically present with an excellent clinical outcome. However there have been
      controversies concerning the prognostic impact of so-called implants, an extra
      ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure
      whether these implants actually resemble metastasis owning the same genetic
      pattern as the ovarian primary or whether they develop independently. METHODS:
      The current study, in the aim of further clarifying the genetic origin of
      implants, assessed BRAF/KRAS hot spot mutations and the p53/p16INK4a
      immunophenotype of s-BOTs and corresponding implants (n=49) of 15 patients by
      pyro-sequencing and immunostaining, respectively. RESULTS: A significant
      proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though
      p16INK4a was found to be abundantly expressed, p53 immunoreactivity was rather
      low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were
      compared no patient presented with a fully matching mutation profile of s-BOTs
      and all corresponding implants. CONCLUSIONS: The current study reveals genetic
      heterogeneity of s-BOTs and implants, as none of the markers examined showed
      constant reciprocity. Hence, our findings may assist to explain the different
      clinical presentation of s-BOTs and implants and might encourage to applying more
      individualized follow up protocols.

PMID- 24139523
TI  - Does CHA2DS2-VASc improve stroke risk stratification in postmenopausal women with
      atrial fibrillation?
AB  - BACKGROUND: Risk stratification of atrial fibrillation patients with a congestive
      heart failure (C), hypertension (H), age >= 75 (A), diabetes (D), stroke or
      transient ischemic attack (TIA) (S2) (CHADS2) score of <2 remains imprecise,
      particularly in women. Our objectives were to validate the CHADS2 and congestive
      heart failure (C), hypertension (H), age >= 75 (A2), diabetes (D), stroke, TIA or
      prior thromboembolic disease (S2)- vascular disease (V), age 65-74 (A), female
      gender (S) (CHA2DS2-VASc) stroke risk scores in a healthy cohort of American
      women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk
      stratifies individuals with a CHADS2 score of <2. METHODS: We identified a cohort
      of 5981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9
      +/- 7.2 years) enrolled in the Women's Health Initiative and followed for a
      median of 11.8 years. Univariate and multivariate proportional hazards analyses
      were used to examine these 2 risk scores, with main outcome measures being
      annualized event rates of ischemic stroke or transient ischemic attack stratified
      by risk score. RESULTS: Annualized stroke/transient ischemic attack rates ranged
      from 0.36% to 2.43% with increasing CHADS2 score (0-4+) (hazard ratio [HR] 1.57;
      95% confidence interval [CI], 1.45-1.71 for each 1-point increase) and 0.20%
      2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50; 95% CI, 1.41-1.60 for
      each 1-point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67
      (95% CI, 0.65-0.69) versus 0.65 (95% CI, 0.62-0.67), P <.01. For CHADS2 scores
      <2, stroke risk almost doubled with every additional CHA2DS2-VASc point.
      CONCLUSIONS: Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk
      in postmenopausal women with atrial fibrillation, CHA2DS2-VASc further risk
      stratifies patients with a CHADS2 score <2.

PMID- 24139524
TI  - Non-O blood type is associated with an increased risk of venous thromboembolism
      after radical cystectomy.
AB  - OBJECTIVE: To evaluate the association of blood type (non-O vs O) with venous
      thromboembolism (VTE) risk after radical cystectomy (RC) for bladder cancer.
      METHODS: From 1980 to 2005, we identified 2076 consecutive patients with RC for
      whom blood type was available in 2008 (96.7%). We evaluated the association of
      blood type with postoperative VTE using logistic regression, controlling for
      patient age, tumor, and nodal stage, Eastern Cooperative Oncology Group (ECOG)
      performance status, body-mass index (BMI), and number of lymph nodes removed at
      surgery. RESULTS: A total of 865 of 2076 patients (41.7%) had O blood type, 1143
      (55.0%) were non-O, and 68 (3.3%) were missing. Median follow-up was 11.1 years,
      during which time VTE developed in 216 patients (10.4%). No significant
      differences were noted between those with O vs non-O blood type regarding patient
      age (median 69 years vs 69, P = .87), ECOG (P = .69), BMI (median 27.5 vs 28.1, P
      = .12), tumor stage (P = .97), pN+ status (15.6% vs 15.2%, P = .79), or number of
      nodes removed (median 9 vs 8, P = .43). On multivariate analysis, non-O blood
      type was associated with a nearly two-fold increased risk of VTE (odds ratio [OR]
      = 1.85, P = .007). CONCLUSION: Non-O blood type was independently associated with
      an increased risk of VTE after RC. These patients should be counseled
      accordingly, and may benefit from increased perioperative prophylaxis.

PMID- 24139525
TI  - Comparison of 3 upper tract anticarcinogenic agent delivery techniques in an ex
      vivo porcine model.
AB  - OBJECTIVE: To evaluate the degree of urothelial exposure using 3 upper tract
      delivery techniques in an ex vivo porcine model, to determine the optimal
      modality to locally deliver topical anticarcinogenic agents in patients with
      upper tract urothelial carcinoma. MATERIALS AND METHODS: An indigo carmine
      solution was infused into en bloc porcine urinary tracts to test the 3
      techniques: antegrade infusion via nephrostomy tube, reflux via indwelling double
      pigtail stent, and retrograde administration via a 5F open-ended ureteral
      catheter. Nine renal units (3 per delivery method) were used. After a 1-hour
      dwell time, the urinary tracts were bivalved and photographed. Each renal unit
      was evaluated by 3 blinded reviewers who estimated the total percentage of
      stained urothelial surface area using a computer-based area approximation system.
      In addition, as a surrogate for exposure adequacy, a validated equation was used
      to calculate the staining intensity at 6 predetermined locations in the upper
      tract, with lower values representing more efficient staining. RESULTS: Mean
      percent of surface area stained for the nephrostomy tube, double-pigtail stent,
      and open-ended ureteral catheter groups was 65.2%, 66.2%, and 83.6%, respectively
      (P = .002). Mean staining intensities were 40.9, 33.4, and 20.4, respectively (P
      = .023). CONCLUSION: Our results suggest that retrograde infusion via open-ended
      ureteral catheter is the most efficient method of upper tract therapy delivery.
      Larger studies using in vivo models should be performed to further validate these
      findings and potentially confirm this method as optimal for delivery of topical
      anticarcinogenic agents in upper tract urothelial carcinoma.

PMID- 24139526
TI  - Quantification of the impact of PSI:Biology according to the annotations of the
      determined structures.
AB  - BACKGROUND: Protein Structure Initiative:Biology (PSI:Biology) is the third phase
      of PSI where protein structures are determined in high-throughput to characterize
      their biological functions. The transition to the third phase entailed the
      formation of PSI:Biology Partnerships which are composed of structural genomics
      centers and biomedical science laboratories. We present a method to examine the
      impact of protein structures determined under the auspices of PSI:Biology by
      measuring their rates of annotations. The mean numbers of annotations per
      structure and per residue are examined. These are designed to provide measures of
      the amount of structure to function connections that can be leveraged from each
      structure. RESULTS: One result is that PSI:Biology structures are found to have a
      higher rate of annotations than structures determined during the first two phases
      of PSI. A second result is that the subset of PSI:Biology structures determined
      through PSI:Biology Partnerships have a higher rate of annotations than those
      determined exclusive of those partnerships. Both results hold when the annotation
      rates are examined either at the level of the entire protein or for annotations
      that are known to fall at specific residues within the portion of the protein
      that has a determined structure. CONCLUSIONS: We conclude that PSI:Biology
      determines structures that are estimated to have a higher degree of biomedical
      interest than those determined during the first two phases of PSI based on a
      broad array of biomedical annotations. For the PSI:Biology Partnerships, we see
      that there is an associated added value that represents part of the progress
      toward the goals of PSI:Biology. We interpret the added value to mean that team
      based structural biology projects that utilize the expertise and technologies of
      structural genomics centers together with biological laboratories in the
      community are conducted in a synergistic manner. We show that the annotation
      rates can be used in conjunction with established metrics, i.e. the numbers of
      structures and impact of publication records, to monitor the progress of
      PSI:Biology towards its goals of examining structure to function connections of
      high biomedical relevance. The metric provides an objective means to quantify the
      overall impact of PSI:Biology as it uses biomedical annotations from external
      sources.

PMID- 24139527
TI  - A systematic review and meta-analysis of randomized controlled trials
      investigating the effects of curcumin on blood lipid levels.
AB  - BACKGROUND & AIMS: Curcumin is a polyphenolic natural compound with diverse and
      attractive biological activities. There has been in-vitro, preclinical and
      clinical evidence on the cardioprotective and lipid-lowering effects of curcumin.
      The present review aimed to systematically review and meta-analyze current
      clinical evidence on the effects of curcumin supplementation on blood lipids.
      METHODS: A comprehensive literature search in Medline, Scopus, AMED, Cochrane and
      clinical trial registry databases was performed to identify randomized controlled
      trials investigating the effect of curcumin on any component of serum lipid
      profile including total cholesterol, low-density lipoprotein cholesterol (LDL-C),
      high-density lipoprotein cholesterol (HDL-C) and triglycerides. Meta-analysis of
      eligible studies was conducted using a random-effects approach. RESULTS: Five
      studies comprising 10 treatment arms (n = 133 in the curcumin and 90 in the
      control group) fulfilled the inclusion criteria. Meta-analysis of findings did
      not indicate a significant effect of curcumin on any of the lipid parameters. The
      estimated pooled mean changes (95% confidence interval) following curcumin
      supplementation were 8.97 (95% CI: -4.56 to 22.51) mg/dL (for total cholesterol;
      p = 0.19); 16.15 (-4.43 to 36.74) mg/dL (for LDL-C; p = 0.12); -0.59 (-1.66 to
      0.49) mg/dL (for HDL-C; p = 0.28) and -1.29 (-9.05 to 6.48) mg/dL (for
      triglycerides; p = 0.75). In the same manner, subgroup analysis of studies on
      patients at cardiovascular risk did not indicate any significant effect of
      curcumin on circulating lipid levels. There was a significant heterogeneity for
      the impact of curcumin on total cholesterol, LDL-C and triglycerides but not HDL
      C. CONCLUSIONS: In light of the present meta-analysis, curcumin supplementation
      has apparently no effect on serum total cholesterol, LDL-C, triglycerides and HDL
      C levels when considering heterogeneous populations. However, further randomized
      controlled trials with longer supplementation duration, and bioavailability
      improved formulations of curcumin are warranted to be conducted in dyslipidemic
      subjects for a more robust assessment of the lipid-modulating properties of this
      phytochemical.

PMID- 24139528
TI  - Explorative analyses on the value of interim PET for prediction of response in
      pediatric and adolescent non-Hodgkin lymphoma patients.
AB  - BACKGROUND: This study is to evaluate the predictive value of FDG-PET (PET) in
      pediatric and adolescent patients suffering from non-Hodgkin lymphoma (pNHL) in
      comparison to information provided by conventional imaging methods (CIM).
      METHODS: Imaging was performed at baseline and at interim (after 2 cycles of
      chemotherapy). The response assessment in PET was carried out visually and semi
      quantitatively, the latter one by use of percentage decrease in SUVmax from
      baseline to interim (DeltaSUVmax). The PET-based results were compared to the
      findings by CIM. Progression-free survival (PFS) was analyzed using Kaplan-Meier
      curves (KM) and log-rank test. RESULTS: The final study included 16 patients
      (mean follow-up time, 60.2 months (range, 4.0 to 85.7 months)). Relapse occurred
      in four patients. Visual PET compared to CIM revealed higher sensitivity (3/4 vs
      1/4) and NPV (6/7 vs 10/13), and equal PPV (3/9 vs 1/3), but lower specificity
      (6/12 vs 10/12) and accuracy (9/16 vs 11/16). False-positive findings in PET at
      interim were predominantly observed in patients presenting bulky disease (5/6),
      whereas CIM was true-negative in all of these cases. KM analyses revealed no
      significant differences in 5-year PFS neither for CIM (76.9% vs 66.7%; p = 0.67)
      nor for visual PET (85.7% vs 66.7%; p = 0.34) nor for DeltaSUVmax (88.9% vs
      57.1%; p = 0.12). CONCLUSIONS: The predictive value of iPET in pediatric patients
      suffering from NHL was limited due to considerably high amount of false-positive
      findings, especially in patients suffering from bulky disease. However, due to
      our limited sample size, final conclusions cannot be drawn and, thus, call for
      further evaluation of PET in pNHL in larger and more homogenous patient series.

PMID- 24139529
TI  - Budding and braking news about clathrin-mediated endocytosis.
AB  - Clathrin-mediated endocytosis (CME) is the predominate mechanism of endocytosis
      in eukaryotes, but an understanding of this mechanism in plants has lagged behind
      yeast and mammalian systems. The generation of Arabidopsis mutant libraries, and
      the development of the molecular tools and equipment necessary to characterize
      these plant lines has led to an astonishing number of new insights into the
      mechanisms of membrane trafficking in plants. Over the past few years progress
      has been made on identifying, and in some instances confirming, the core
      components of CME in plants. This review focuses on the recent progress made in
      the understanding of the mechanism and regulation of CME in plants. 

PMID- 24139530
TI  - Pushing the boundaries of stroke therapy for children.

PMID- 24139531
TI  - Endovascular treatment of children with cerebral venous sinus thrombosis: a case
      series.
AB  - BACKGROUND: Cerebral venous sinus thrombosis is a potentially serious condition
      affecting 0.56 to 0.67 per 100,000 children annually; adverse outcomes are
      common. The standard of care is anticoagulation with heparin. A proportion of
      patients, however, remain in a severe clinical condition and in these,
      endovascular therapy is an alternative treatment. There is little published
      literature on the use of endovascular treatments in children with cerebral venous
      sinus thrombosis. METHODS: We retrospectively reviewed case notes and imaging in
      a consecutive series of nine children treated using endovascular therapy after
      diagnosis of cerebral venous sinus thrombosis. Clinical presentation, decision to
      escalate therapy, methods of recanalization, and clinical outcome were assessed.
      RESULTS: Nine children were treated (age range 18 months to 16 years). Diagnosis
      was made by computed tomography, computed tomography venography, magnetic
      resonance imaging, or magnetic resonance venography. Seven children were in a
      coma; one had signs of raised intracranial pressure with progressive cranial
      nerve palsies; and one was drowsy with a fluctuating hemiparesis. Eight children
      had been treated with heparin without improvement. Several endovascular methods
      were used including local tissue plasminogen activator, microguidewire and
      catheter disruption, balloon angioplasty, and thromboaspiration using the
      Penumbra device. Eight children had good functional outcomes. One child died as a
      result of uncontrolled intracranial hypertension secondary to cerebral venous
      sinus thrombosis. CONCLUSION: Endovascular therapy may have a role in the
      treatment of cerebral venous sinus thrombosis in children when medical therapy
      has failed and the patient is in a poor clinical condition.

PMID- 24139532
TI  - Thrombolysis for children with acute ischemic stroke: a perspective from the
      kids' inpatient database.
AB  - BACKGROUND: Thrombolysis for acute ischemic stroke (AIS) in children is yet to be
      proven efficacious, and there is limited information about its safety in large
      pediatric samples. Here we evaluate the safety outcomes associated with
      thrombolysis in children as well as the trend of hospital utilization over the
      past decade in the United States. METHODS: A cohort of children with acute
      ischemic stroke was identified from the Kids' Inpatient Database for the years
      1998-2009. Acute ischemic stroke was identified by the International
      Classification of Diseases-9 clinical classification software codes (109 and
      110). Multivariate logistic regression analyses were used to assess covariates
      associated with outcomes of hospital mortality and intracerebral hemorrhage. The
      Cochran-Armitage test was employed for linear trend of discrete variables.
      RESULTS: In this analysis, 9257 children were admitted with the diagnosis of
      acute ischemic stroke; only 67 (0.7%) received thrombolysis. Thrombolysis-treated
      children were older than the rest of the cohort (13.1 +/- 7.3 vs 8.18 +/- 7.5; P
      < 0.0001) and they had a longer hospital stay (median 11 vs 6 days; P < 0.0001).
      Gender, race, and family income approximated by postal code were similar among
      the treated and untreated children. Unadjusted analysis showed higher hospital
      mortality (10.45% vs 6.14%; P = 0.06) and intracerebral hemorrhage (2.99% vs
      0.77%; P = 0.08) in the thrombolysis group. Adjusted analysis showed that
      intracerebral hemorrhage is predictive of a higher hospital mortality (odds ratio
      3.43; 95% confidence interval 1.89-6.22), whereas thrombolysis was not (odds
      ratio 1.78; 95% confidence interval 0.86-3.64). The overall rate of thrombolysis
      per 3 years intervals had increased from 5.2 to 9.7 per 1000 children with acute
      ischemic stroke (P = 0.02). This increase was mainly seen in non-children
      hospitals (P = 0.01). CONCLUSION: Thrombolysis for acute ischemic stroke is
      infrequently used in children. There is a trend toward higher risks of
      intracerebral hemorrhage and hospital mortality, although these risks are as low
      as those reported in adult population. The hospitals' utilization of thrombolysis
      in children has increased during the study period.

PMID- 24139533
TI  - Deficits in elbow position sense in neonatal brachial plexus palsy.
AB  - BACKGROUND: In neonatal brachial plexus palsy, sensory recovery is thought to
      exceed motor recovery with little attention paid to long-term assessment of
      proprioceptive ability. However, there is growing evidence that reduced
      somatosensory function frequently accompanies motor deficits as a result of
      activity-dependent changes in the central nervous system. Given the importance of
      proprioception in everyday motor activities, this study was designed to
      investigate position sense about the elbow joint in neonatal brachial plexus
      palsy. METHODS: A convenience sample of seven individuals with neonatal brachial
      plexus palsy aged 9-17 years and in seven control individuals aged 10-16 years
      were recruited for the study. An elbow position matching task was used in which
      passive displacement of the forearm (reference arm) was reproduced with the same
      or opposite arm. In both conditions, matching was performed in the absence of
      vision and required utilization of position-related proprioceptive feedback.
      RESULTS: Position-matching errors were significantly greater for the affected
      versus the unaffected arm when reproducing a reference position with the same
      arm. When matching was performed using the opposite arm, errors were dependent
      upon which arm served as the reference arm. When the unaffected arm served as the
      reference position, affected arm matching errors were not significantly different
      from control values. However, in the reverse situation, in which the unaffected
      arm relied on reference feedback from the affected arm, matching errors doubled
      compared with control values. CONCLUSIONS: These results provide evidence that
      position sense is impaired in neonatal brachial plexus palsy and illustrate the
      importance of assessing proprioception in this population.

PMID- 24139534
TI  - Topiramate for Tourette's syndrome in children: a meta-analysis.
AB  - OBJECTIVES: To assess the efficacy and safety of topiramate for children with
      Tourette syndrome. METHODS: Randomized controlled trials evaluating topiramate
      for children with Tourette syndrome were identified from the Cochrane library,
      PubMed, Cochrane Central, Embase, CBM, CNKI, VIP, WANG FANG database, and
      relevant reference lists. Two reviewers independently selected trials, assessed
      trial quality, and extracted the data. Disagreement was resolved by discussion.
      Quality assessment referred to the Cochrane Handbook for Systematic Reviews of
      Interventions (version 5.0.1.). RESULTS: Fourteen trials involving 1003 patients
      were included, of which 720 cases were male (71.8%). Ages were 2 to 17 years old.
      The general quality of included randomized controlled trials was poor. All trials
      were positive drug-controlled (12 randomized controlled trials used haloperidol
      as control, 2 used tiapride). The follow-up period was from 20 days to 12 months.
      Meta-analysis of 3 trials (n = 207), in which tics symptoms control was assessed
      by Yale Global Tic Severity Scale, suggested that there was significant
      difference in the mean change of Yale Global Tic Severity Scale score during the
      treatment period (mean difference = -7.74, 95% CI [-10.49, -4.99], I(2) = 0)
      between topiramate and control groups. Meta-analysis of 9 trials (n = 668)
      evaluating tics symptoms control >= 50% suggested that there was no significant
      difference in reduction of tics between topiramate and control group during the
      treatment period (relative ratio = 1.36, 95% CI [0.90, 2.06], I(2) = 0). Adverse
      events were reported in 13 trials. Drowsiness (3.3-16%), loss of appetite (4
      16.7%), cognitive dysfunction (7.89-12.5%), and weight loss (6-10.5%) were common
      adverse events. CONCLUSIONS: The current evidence is promising but not yet
      sufficient to support the routine use of topiramate for Tourette syndrome in
      children due to low quality of the study designs. It deserves to confirm in
      further high-quality, placebo-controlled trials.

PMID- 24139535
TI  - Nocturnal headaches and pulsatile cranial mass: the tip of an iceberg.
AB  - BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) disorder
      is a newly defined hereditary disorder of the vasculature with typical defining
      features that include cutaneous capillary malformations associated with high-flow
      lesions in various other organ systems. Mutations on the RASA1 gene are reported
      to be associated with a variety of vascular malformations and present with a
      widely varying phenotype. PATIENT: A healthy 3 year old presented with acute
      onset of severe nocturnal headaches, nausea, and vomiting associated with a 2-cm
      pulsatile mass and prominent superficial veins on her forehead. Neuroimaging
      demonstrated a complex vascular malformation with multiple arteriovenous fistulae
      and cavernous angiomas present in multiple locations in the brain, but not in any
      other organ system. RESULTS: The patient was found to have a mutation of the
      RASA1 gene, which has not been previously described in the literature.
      CONCLUSIONS: This case describes a new RASA1 mutation with a phenotype that has
      not been previously described with a combination of pial fistulae and
      intracranial AV fistula in the absence of arteriovenous malformations.

PMID- 24139536
TI  - Eye and brain abnormalities in congenital muscular dystrophies caused by fukutin
      related protein gene (FKRP) mutations.
AB  - BACKGROUND: Mutations in the fukutin-related protein gene account for a broad
      spectrum of phenotypes ranging from severe congenital muscular dystrophies to a
      much milder limb-girdle muscular dystrophy 2I. The involvement of the eyes is
      variable, with most patients having normal eye examination. OBJECTIVES: We
      describe eye and brain abnormalities in a 16 month-old-boy with Walker-Warburg
      syndrome phenotype resulting from a novel fukutin-related protein gene mutation
      in exon 4 and compare these with other reported patients with fukutin-related
      protein gene mutation. METHODOLOGY: All patients with reported fukutin-related
      protein gene mutations who had eye involvement were included. Their clinical
      features, brain magnetic resonance imaging, and eye findings were compared with
      our patient. CONCLUSIONS: Patients with fukutin-related protein gene mutation
      tend to have no or mild eye involvement (generally strabismus), with very few
      cases reported of moderate to severe eye involvement. Our patient with a novel
      mutation c.558dupC(p.Ala187fs) represents one of the most severe phenotypes
      described in regard to eye involvement.

PMID- 24139537
TI  - Successful clinical treatment of child stroke using mechanical embolectomy.
AB  - BACKGROUND: Stroke in childhood is less common than stroke in adults, but recent
      study estimate incidences up to 13/100,000. Mortality is decreasing but morbidity
      remains very high, with variable effects for two thirds of patients. Recent
      guidelines for optimal treatment in childhood stroke recommend advise against the
      use of thrombolysis, except for specific research protocols. There is no
      recommendation about intra-arterial thrombolysis or mechanical embolectomy.
      Various investigators have published cases of mechanical embolectomy in adult
      stroke, and a few cases of children are also reported. PATIENT: We report a case
      of mechanical embolectomy 6 hours after a basilar artery occlusion in a healthy 7
      year-old child. RESULT: He presented a successful medical outcome and had made a
      complete recovery. CONCLUSION: This patient and the 10 published pediatric cases
      suggest mechanical embolectomy can be successfully used to treat basilar artery
      occlusion in children with coordination of neurology and interventional radiology
      services.

PMID- 24139538
TI  - Response to Losurdo et al.

PMID- 24139539
TI  - Impact of bubble size in a rat model of cerebral air microembolization.
AB  - BACKGROUND: Cerebral air microembolization (CAM) is a frequent side effect of
      diagnostic or therapeutic interventions. Besides reduction of the amount of
      bubbles, filter systems in the clinical setting may also lead to a dispersion of
      large gas bubbles and therefore to an increase of the gas-liquid-endothelium
      interface. We evaluated the production and application of different strictly
      defined bubble diameters in a rat model of CAM and assessed functional outcome
      and infarct volumes in relation to the bubble diameter. METHODS: Gas emboli of
      defined number and diameter were injected into the carotid artery of rats. Group
      I (n = 7) received 1800 air bubbles with a diameter of 45 MUm, group II (n = 7)
      40 bubbles of 160 MUm, controls (n = 6) saline without gas bubbles; group I and
      II yielded the same total injection volume of air with 86 nl. Functional outcome
      was assessed at baseline, after 4 h and 24 h following cerebral MR imaging and
      infarct size calculation. RESULTS: Computer-aided evaluation of bubble diameters
      showed high constancy (group I: 45.83 MUm +/- 2.79; group II: 159 MUm +/- 1.26).
      Animals in group I and II suffered cerebral ischemia and clinical deterioration
      without significant difference. Infarct sizes did not differ significantly
      between the two groups (p = 0.931 u-test). CONCLUSIONS: We present further
      development of a new method, which allows reliable and controlled CAM with
      different bubble diameters, producing neurological deficits due to unilateral
      cerebral damage. Our findings could not display a strong dependency of stroke
      frequency and severity on bubble diameter.

PMID- 24139540
TI  - Addressing mental health issues in primary care: an initial curriculum for
      medical residents.
AB  - OBJECTIVE: Many express concern that modern medicine fails to provide adequate
      psychosocial and mental health care. Our educational system has not trained the
      primary care providers who care for most of these patients. Our objective here is
      to propose a quantum change: prepare residents and students during all years of
      training so that they are as effective in treating psychosocial and mental health
      issues as they are medical problems. METHOD: We operationalize this objective,
      following Kern, by developing an intensive 3-year curriculum in psychosocial and
      mental health care for medical residents based on models with a strong evidence
      base. RESULTS: We report an intensive curriculum that can guide others with
      similar training interests and also initiate the conversation about how best to
      prepare residency graduates to provide effective mental health and psychosocial
      care. CONCLUSION: Identifying specific curricula informs education policy-makers
      of the specific requirements they will need to meet if psychosocial and mental
      health training are to improve. PRACTICE IMPLICATIONS: Training residents in
      mental health will lead to improved care for this very prevalent primary care
      population.

PMID- 24139541
TI  - Neo-adjuvant chemotherapy for cervical cancer in pregnancy: a case report and
      literature review.
AB  - Managing women who are pregnant and with a diagnosis of cervical cancer has many
      complex challenges. This case report describes the diagnosis and management of a
      patient presenting in her first trimester with stage 2B cervical cancer. In
      conjunction with this a literature review was undertaken using the following
      databases from the years 1970-2010: Embase, CINAHL, Medline and DARE. We examined
      the number of cases reported in the literature in which chemotherapy also was
      used in pregnant women with a cervical malignancy. Twenty-four papers were
      retrieved describing in total (including the present case) 35 cases of cervical
      cancer in pregnancy treated with this modality. Cisplatin therapy would seem the
      most reliable form of treatment, permitting a good outcome for most patients. The
      effect of delaying radiotherapy to permit pregnancy to fetal viability in larger
      tumours cannot be elucidated. 

PMID- 24139542
TI  - Induction of labor for term small-for-gestational-age fetuses: what are the
      consequences?
AB  - OBJECTIVE: To evaluate whether early term labor induction for suspected
      intrauterine growth restriction (weeks 37-39) improves neonatal outcome for small
      for-gestational-age (SGA) neonates. STUDY DESIGN: Delivery room data for 2004
      2008 from a single tertiary medical center were linked to neonatal discharge data
      from the same institution. Data were limited to all singleton, liveborn SGA
      neonates born at 37-42 weeks of gestation and their mothers. Births with known
      congenital anomalies were excluded. Women undergoing induction of labor for
      suspected growth restriction between 37 and 39 weeks' gestation (early induction
      SGA) were compared with women who gave birth to term SGA neonates without early
      induction. SGA (<10th percentile for gestational age and gender) was used as a
      surrogate for intrauterine growth restriction. Associations between early term
      labor induction and neonatal morbidities were estimated using logistic
      regression. RESULTS: A total of 2378 SGA neonates meeting study criteria were
      identified. Of these, 445 underwent early term induction and 1933 were in the non
      early induction SGA group. Intrauterine demise among term (37-42 weeks) SGAs
      occurred in one case at 37 weeks. Early term induction for SGA was associated
      with an increased risk of cesarean delivery. Several neonatal complications,
      including hyperbilirubinemia, hypoglycemia and respiratory complications were
      more prevalent in the early induction SGA group. The increased odds for neonatal
      complications persisted after controlling for possible confounders. CONCLUSIONS:
      Early term induction for SGA fetuses results in an increased risk of cesarean
      deliveries as well as neonatal metabolic and respiratory complications, with no
      apparent neonatal benefit.

PMID- 24139543
TI  - How to avoid uterine necrosis after arterial embolization for post-partum
      hemorrhage: a proposal based on a single center experience of 600 cases.

PMID- 24139544
TI  - Context-dependent movement behavior of woodland salamanders (Plethodon) in two
      habitat types.
AB  - Animal movement is critical to the maintenance of functional connectivity at the
      landscape scale and can play a key role in population persistence and
      metapopulation dynamics. The permeability of habitat to animal movement may vary
      as a result of either differential mortality, physical resistance, or simply the
      behavioral responses of organisms to perceived habitat quality. Understanding how
      and when animal movement behavior varies among habitat types is critical for
      identifying barriers to dispersal and predicting species distributions in
      relation to landscape features. We conducted an experimental translocation study
      and compared the movement success and behavioral strategies of plethodontid
      salamanders in both forest and open-canopy habitat. We found that individuals in
      closed-canopy forest oriented more strongly towards their home ranges and moved
      significantly farther on their release night. In spite of the clear differences
      in movement paths, the ultimate movement success of homing salamanders did not
      appear to vary with habitat type. Our study contributes to a growing body of
      literature suggesting the importance of recognizing the context dependence of
      animal movement behavior. Because the movement rates of displaced salamanders
      were significantly reduced in open-canopy, dispersal rates of plethodontid
      salamanders in open-canopy habitat are likely lower than in control forest.
      Further mechanistic studies focusing on habitat-specific movement behavior and
      survival costs will be valuable for effectively identifying and mitigating
      barriers to animal movement. 

PMID- 24139545
TI  - Consumption of sweetened, dried cranberries may reduce urinary tract infection
      incidence in susceptible women--a modified observational study.
AB  - BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial
      infections, and over 50% of women will have a UTI during their lifetimes.
      Antibiotics are used for prophylaxis of recurrent UTIs but can lead to emergence
      of drug-resistant bacteria. Therefore, it is reasonable to investigate
      nutritional strategies for prevention of UTIs. Cranberry juices and supplements
      have been used for UTI prophylaxis, but with variable efficacy. Because dried
      cranberries may contain a different spectrum of polyphenolics than juice,
      consuming berries may or may not be more beneficial than juice in decreasing the
      incidence of UTIs in susceptible women. The primary objectives of this study were
      to determine if consumption of sweetened, dried cranberries (SDC) decreases
      recurrent UTIs and whether this intervention would alter the heterogeneity,
      virulence factor (VF) profiles, or numbers of intestinal E. coli. METHODS: Twenty
      women with recurrent UTIs were enrolled in the trial and consumed one serving of
      SDC daily for two weeks. Clinical efficacy was determined by two criteria, a
      decrease in the six-month UTI rates pre- and post-consumption and increased time
      until the first UTI since beginning the study. Strain heterogeneity and virulence
      factor profiles of intestinal E. coli isolated from rectal swabs were determined
      by DNA fingerprinting and muliplex PCR, respectively. The numbers of intestinal
      E. coli eluted from rectal swabs pre- and post-consumption were also quantified.
      RESULTS: Over one-half of the patients did not experience a UTI within six months
      of SDC consumption, and the mean UTI rate per six months decreased significantly.
      Kaplan-Meier analysis of infection incidence in women consuming SDC compared to
      patients in a previous control group showed a significant reduction in time until
      first UTI within six months. The heterogeneity, VF profiles, and prevalence of
      intestinal E. coli strains were not significantly different after cranberry
      consumption. CONCLUSIONS: Results of this study indicate a beneficial effect from
      consuming SDC to reduce the number of UTIs in susceptible women. Because there
      were no changes in the heterogeneity or VF profiles of E. coli, additional
      studies are needed to determine the mechanism of action of SDC for reduction of
      UTIs.

PMID- 24139546
TI  - Synchronous primary neoplasms of the bladder, skin and breast in a male patient:
      a case report.
AB  - The incidence of multiple primary malignant neoplasms increases with age,
      reflecting an increase in overall cancer risk in older patients. Cases of two or
      more concurrent primary cancers are still rare, although its incidence is
      increasing. Here, we report the case of a 57-year-old man who was referred to our
      institution with synchronous squamous cell carcinoma of the skin on the forehead,
      infiltrating ductal carcinoma of the breast, and transitional cell carcinoma of
      the urinary bladder. To the best of our knowledge, this is the first reported
      case in literature of this combination of primary neoplasms.

PMID- 24139547
TI  - Inactivation of the paraventricular thalamus abolishes the expression of cocaine
      conditioned place preference in rats.
AB  - BACKGROUND: The paraventricular thalamus (PVT) is rapidly becoming recognized as
      part of the addiction circuitry. In addition to its strong anatomical connection
      to most of the brain regions underlying addiction, such as the nucleus accumbens,
      prefrontal cortex, amygdala, and hippocampus, the PVT has recently been shown to
      contribute to cocaine sensitization and reinstatement. In the present study, we
      examined the role of the PVT in the expression of cocaine conditioned place
      preference (CPP). METHODS: We tested the impact of PVT inactivation by
      baclofen/muscimol (bac-mus) microinjection on the expression of cocaine-induced
      CPP in rats. Rats were implanted with guide cannulae into the PVT. Bac-mus (GABAB
      GABAA agonists) or saline was injected into the PVT prior to CPP testing.
      RESULTS: Inactivation of the PVT by bac-mus prevented the expression of CPP,
      while placements outside the PVT did not affect CPP. Intra-PVT injections of bac
      mus did not affect locomotor activity during the session. CONCLUSIONS: In the
      present study, we contribute to the growing body of research supporting a role
      for the PVT in addiction by demonstrating that the PVT is necessary for the
      expression of cocaine CPP.

PMID- 24139548
TI  - Hospital-admitted COPD patients treated at home using telemedicine technology in
      The Virtual Hospital Trial: methods of a randomized effectiveness trial.
AB  - BACKGROUND: Recent reviews suggest that telemedicine solutions for patients with
      chronic obstructive pulmonary disease (COPD) may prevent hospital readmissions
      and emergency room visits and improve health-related quality of life. However,
      the studies are few and only involve COPD patients who are in a stable phase or
      in-patients who are ready for discharge. COPD patients hospitalized with an acute
      exacerbation may also benefit from telemedicine solutions. The overall aim is to
      investigate a telemedicine-based treatment solution for patients with acute
      exacerbation of COPD at home as compared to conventional hospital treatment
      measured according to first treatment failure, which is defined as readmission
      due to COPD within 30 days after discharge. METHODS: COPD patients with acute
      exacerbation who fulfilled the eligibility criteria and were from two university
      hospitals in Denmark were randomized (1:1) by computer-generated tables that
      allocated treatments in blocks of four to receive either standard treatment at
      the hospital or the same standard treatment at home using telemedicine technology
      (that is, a video conference system with a touch screen and webcam and monitoring
      equipment (spirometer, thermometer, and pulse oximeter)). Patients treated in the
      telemedicine group were backed up by an organizational setting securing 24/7/365
      online access to the hospital, as well as access to oxygen, nebulizer therapy,
      oral medical therapy and surveillance of vital parameters from home monitoring
      devices. Patients in both groups were discharged when clinically stable and when
      fulfilling five pre-specified discharge criteria. Follow-up was performed at 1, 3
      and 6 months after discharge. RESULTS: Enrollment of patients started in June
      2010 and ended in December 2011. Follow-up ended in May 2012. Results were
      analyzed in 2013. CONCLUSIONS: The results may have implications on future
      hospital treatment modalities for patients with severe exacerbations in COPD
      where telemedicine may be used as an alternative to conventional admission. TRIAL
      REGISTRATION: Clinical Trials NCT01155856.

PMID- 24139549
TI  - Castration-resistant prostate cancer: adaptive responses in the androgen axis.
AB  - The androgen signaling axis in prostate cancer is associated with multiple
      adaptive mechanisms in response to castration. Herein we review these adaptations
      with an emphasis on recent molecular insights into the growth and development of
      castration resistant prostate cancer (CRPC). Alterations include both
      conventional and novel intracrine androgen synthesis pathways and androgen
      transport as well as androgen receptor (AR) overexpression, mutation, and splice
      variation. Each of these underlying mechanisms are potentially linked to post
      castration growth, especially after treatment with newer hormonal agents such as
      abiraterone and enzalutamide. Post-translational AR modifications are well
      documented and these can affect receptor activity, stability, localization, and
      interaction with other proteins. Changes in recruitment of androgen receptor
      associated co-activators/repressors and a distinct AR-induced transcriptional
      program can dramatically alter proliferation, invasion, and metastasis in a
      ligand and context-dependent manner. Numerous previously uncharacterized non
      coding RNAs, some of which are androgen regulated, may also have important
      biological function in this disease. Taken together, the view of CRPC has changed
      dramatically in the last several years. This has occurred not only within the
      setting of multiple treatment paradigm changes, but also as a multiplicity of
      potential molecular mechanisms underlying this disease state have been explored
      and discovered. 

PMID- 24139551
TI  - Commentary: Feedback activities of instructors during a trauma surgery course.

PMID- 24139550
TI  - Germline mutation in the RAD51B gene confers predisposition to breast cancer.
AB  - BACKGROUND: Most currently known breast cancer predisposition genes play a role
      in DNA repair by homologous recombination. Recent studies conducted on RAD51
      paralogs, involved in the same DNA repair pathway, have identified rare germline
      mutations conferring breast and/or ovarian cancer predisposition in the RAD51C,
      RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs
      (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast
      and ovarian cancer predisposition. METHODS: The study was conducted on 142
      unrelated patients with breast and/or ovarian cancer either with early onset or
      with a breast/ovarian cancer family history. Patients were referred to a French
      family cancer clinic and had been previously tested negative for a BRCA1/2
      mutation. Coding sequences of the five genes were analysed by EMMA (Enhanced
      Mismatch Mutation Analysis). Detected variants were characterized by Sanger
      sequencing analysis. RESULTS: Three splicing mutations and two likely deleterious
      missense variants were identified: RAD51B c.452 + 3A > G, RAD51C c.706-2A > G,
      RAD51C c.1026 + 5_1026 + 7del, RAD51B c.475C > T/p.Arg159Cys and XRCC3 c.448C >
      T/p.Arg150Cys. No RAD51D and XRCC2 gene mutations were detected. These mutations
      and variants were detected in families with both breast and ovarian cancers,
      except for the RAD51B c.475C > T/p.Arg159Cys variant that occurred in a family
      with 3 breast cancer cases. CONCLUSIONS: This study identified the first RAD51B
      mutation in a breast and ovarian cancer family and is the first report of XRCC3
      mutation analysis in breast and ovarian cancer. It confirms that RAD51 paralog
      mutations confer breast and ovarian cancer predisposition and are rare events. In
      view of the low frequency of RAD51 paralog mutations, international collaboration
      of family cancer clinics will be required to more accurately estimate their
      penetrance and establish clinical guidelines in carrier individuals.

PMID- 24139552
TI  - Patient experiences after hospitalizations for elective surgery.
AB  - BACKGROUND: Little is known from patients' perspective about the quality of
      postdischarge care and the causes of rehospitalization after elective surgery.
      METHODS: A prospective observational cohort study was conducted. RESULTS: Of 400
      patient participants, 374 completed the 30-day follow-up questionnaire
      (completion rate, 94%). Half of all unplanned rehospitalizations (experienced by
      13% of patients) and nonrehospitalization emergency department visits
      (experienced by 6%) occurred within 10 days of discharge. Patients used emergency
      departments and were rehospitalized at facilities near their homes (mean distance
      traveled, 12.1 mi). The most common primary reason for rehospitalization was
      postoperative complications, according to patient report, clinical records, and
      administrative data. Poor perceived care coordination was associated with higher
      readmission risk. CONCLUSIONS: Patients perceive surgical complications as
      dominating the reasons for rehospitalizations after elective surgery. Strategies
      to improve care quality around elective surgery at referral centers should target
      the discharge process and the coordinated management of postoperative
      complications through care received at regional hospitals.

PMID- 24139553
TI  - The better effect of Roux-en-Y gastrointestinal reconstruction on blood glucose
      of nonobese type 2 diabetes mellitus patients.
AB  - BACKGROUND: Given the role of gastrointestinal reconstruction, we investigated
      whether Roux-en-Y gastrointestinal reconstruction (RYGR) and Billroth I
      reconstruction (B1R) can improve glucose in nonobese type 2 diabetes mellitus
      patients. METHODS: Seventy-six nonobese type 2 diabetes mellitus patients
      underwent open subtotal gastrectomy with RYGR and B1R between January 2005 and
      January 2010 in our hospital. Besides demographic data, preoperative weight,
      glucose, hemoglobin A1c, ghrelin, and glucagon-like peptide 1 were determined.
      RESULTS: As defined previously, 2 of 35 patients with RYGR were cured, 5 patients
      were controlled, and 10 patients were improved; similarly, 2 of 41 patients with
      B1R were controlled, and 3 patients improved 12 months after surgery. The fasting
      glucose and hemoglobin A1c decreased more significantly in RYGR patients (P <
      .05). Moreover, a higher fasting plasma GLP-1 level in RYGR patients and lower
      ghrelin in B1R patients were noted after surgery (P < .05). CONCLUSIONS: RYGR
      shows a more effective amelioration in nonobese type 2 diabetes mellitus
      patients.

PMID- 24139554
TI  - Antiplatelet and anticoagulation medications and the surgical patient.
AB  - BACKGROUND: Acute coronary syndrome affects more than 750,000 Americans per year,
      and antiplatelet agents are the cornerstones of treatment. Atrial fibrillation
      affects 2.4 million patients in the United States, and venous thromboembolism
      occurs in 1 to 2 per 1,000 adults per year. Anticoagulants are commonly
      prescribed to affected patients. Surgeons are commonly called upon to care for
      patients taking medications that affect normal coagulation. It is important that
      the surgical community has a fundamental understanding of these agents'
      pharmacology, which may impact patients' clinical course. METHODS: A review of
      recent literature on pharmacologic agents that affect coagulation was performed.
      RESULTS: A number of medications that alter normal coagulation were reviewed in
      this article including their pharmacologic properties and reversal strategies.
      CONCLUSIONS: There are a variety of medications that affect a patient's
      coagulation ability, including many newer agents on the market. This review
      provides surgeons with the knowledge needed to assist in caring for individuals
      receiving these drugs.

PMID- 24139555
TI  - Obesity, outcomes and quality of care: body mass index increases the risk of
      wound-related complications in colon cancer surgery.
AB  - BACKGROUND: Obese patients may face higher complication rates during surgical
      treatment of colon cancer. The aim of this study was to measure this effect at a
      high-volume tertiary care center. METHODS: All patients with colon cancer treated
      surgically at a single center from 2004 through 2011 were reviewed. Multivariate
      regression assessed relationships of complications and stay outcomes with body
      mass index (BMI) controlling for age, gender, comorbidity score, surgical
      approach, and history of smoking. RESULTS: In 1,048 included patients, BMI was a
      predictor of several complications in both laparoscopic and open procedures. For
      every increase of BMI by one World Health Organization category, the odds ratios
      were 1.61 (P < .001) for wound infection and 1.54 (P < .001) for slow healing.
      Additionally, right colectomies had an odds ratio of 3.23 (P = .017) for wound
      dehiscence. No further associations with BMI were found. CONCLUSIONS: BMI was
      incrementally associated with wound-related complications, illustrating how the
      proliferation of obesity relates to a growing risk for surgical complications. As
      the surgical community strives to improve the quality of care, patient
      controllable factors will play an increasingly important role in cost containment
      and quality improvement.

PMID- 24139556
TI  - Transient interhemispheric disconnection in a case of insulinoma-induced
      hypoglycemic encephalopathy.
AB  - We report a case of a 22-year-old male who was transferred to our hospital in a
      comatose state following successive seizures. Low blood glucose had been detected
      upon his arrival at the previous hospital. He became responsive 12 days after the
      onset of coma. Upon regaining consciousness he exhibited severe dysarthria and
      several interhemispheric disconnection signs such as intermanual conflict, left
      hand dysgraphia, left hemispatial neglect confined to the right hand, impaired
      interhemispheric transfer, and unilateral constructional apraxia of the right
      hand. Brain MRI disclosed T2-weighted and diffusion-weighted hyperintense lesions
      with reduced apparent diffusion coefficients in the bilateral centrum semiovale,
      splenium of the corpus callosum, right posterior limb of the internal capsule,
      and bilateral middle cerebellar peduncles. As the MRI findings vanished, his
      interhemispheric disconnection signs gradually resolved. Abdominal imaging
      studies revealed a pancreatic tumor, which was later endocrinologically diagnosed
      as an insulinoma. This is an extremely rare report of interhemispheric
      disconnection signs due to hypoglycemic encephalopathy. The lesions in the
      bilateral centrum semiovale likely contributed to the interhemispheric
      disconnection signs.

PMID- 24139557
TI  - [Comparison of bedside ultrasound and chest x-ray for inserting central lines].

PMID- 24139559
TI  - [Nutrition recommendations for children who practice sports].
AB  - Several health benefits have been attributed to sports practice, and an adequate
      nutrition status helps to maintain an optimal performance. Children most
      frequently practice non-competitive and non-endurance activities in a school
      setting. The dietary intake of children who practice sports should be similar to
      the general population, properly meeting their energy and nutrient requirements.
      During the activity performance, correct hydration should be aimed for, with
      water appearing to be an adequate source in most cases. General calorie and
      micronutrient supplementation should not be commonly recommended in children.
      Paediatricians must control nutritional status and dietary habits of children who
      practice sports, especially in those cases when weight-loss is aimed for, as well
      as take into account the psychological implications of competitive sports
      practice. 

PMID- 24139558
TI  - [Hydrocortisone for the treatment of refractory hypotension: a randomized
      controlled trial].
AB  - INTRODUCTION: Systemic hypotension is a common sign in critically sick infants.
      Several studies have suggested that the use of short series of corticosteroids
      increases arterial blood pressure and reduces the inotropic support needs in
      preterm neonates with hypotension. There are a small number of reports on the use
      of hydrocortisone (HC) for the treatment of refractory hypotension in infants.
      MATERIAL AND METHODS: To assess the effectiveness of hydrocortisone in the
      reduction of inotropic support in infants with refractory hypotension.
      POPULATION: infants who required dopamine >= 14 MUg/kg/min and/or epinephrine.
      DESIGN: prospective, controlled, randomized, double blind trial with placebo.
      INTERVENTION HC: 2.5mg/kg every 12 hours, for 48 hours intravenously
      (intervention group [IG]); placebo: isotonic saline 1.25 ml/kg/doses
      intravenously (placebo group [PG]) every 12 hours, for 48 hours. Randomization
      was performed in blocks with blind assignment. RESULTS: A total of 50 infants
      with refractory systemic hypotension were prospectively recruited. Patient
      characteristics were similar in both groups. Requirements for inotropic support
      at 48 hrs were achieved in 60%, of the IG versus 24% of the PG (P=.009, RR: 2.5,
      95% CI, 1.16-5.38). A significant association was observed between the
      administration of HC in infants treated with epinephrine and the presence of
      hyperglycemia (P =.008). CONCLUSION: In patients with refractory hypotension
      hydrocortisone administration reduced the need for inotropic support. Further
      studies with a greater number of patients are needed to confirm the effectiveness
      of HC as a therapeutic tool in these infants.

PMID- 24139560
TI  - [Demands and expectations of parents who refuse vaccinations and perspective of
      health professional on the refusal to vaccinate].
AB  - OBJECTIVES: To examine the opinions, beliefs and attitudes about vaccination, of
      parents who decide not to vaccinate their children. To determine the opinions and
      attitudes of the health professionals on the behaviour towards childhood
      vaccination. METHOD: Qualitative research based on semi-structured interviews and
      focal groups in Granada, Spain, including parents who chose to not vaccinate
      their children, and healthcare professionals who can provide a technical point of
      view. An analysis was made of the semantic content, and answers were categorized
      in thematic units. RESULTS: The parents argued on the benefit of suffering
      vaccine-preventable diseases in a natural way, without non-natural, aggressive or
      toxic products. Vaccination was considered unnecessary, if given adequate
      hygienic-sanitary conditions, effectiveness unproven and more dangerous than the
      diseases they prevent, especially the polyvalent vaccines. They believed that
      vaccination programs are moved by biased studies and interests other than
      prevention. Health care professionals believe that they had fears without
      scientific basis, which requires improving information systems. CONCLUSIONS: Non
      vaccinators are unaware of the benefit/risk ratio between the vaccination and the
      individual risk for preventable diseases, and ask for informed consent. Health
      care professionals believe that non-vaccinators' arguments are not correctly
      contrasted and expose the existence of failures in actual vaccination coverage
      and information registration systems. It was suggested to centralize registers
      and compare them in schools, working with local leaders and reporting regularly
      on the status of vaccine-preventable diseases.

PMID- 24139561
TI  - [Obesity and overweight. An assessment of the effectiveness of a public health
      intervention].
AB  - INTRODUCTION: The prevalence of excess weight (obesity and overweight) is
      increasing in developed countries, with preventive measures not shown to be
      sufficiently effective. The aim of this study was to investigate the
      effectiveness of the sustained prevention and treatment by Primary Care
      Paediatrics of overweight from early childhood. MATERIAL AND METHODS: The BMI of
      1669 patients from two Paediatric Teams, were compared using four different age
      intervals between 4 and 14 years during 2007-2009. One of the teams had spent 15
      years carrying out a systematic strategy aimed at the prevention and monitoring
      of overweight. RESULTS: The BMI means in this study were higher than those shown
      in the 1988 Orbegozo tables, particularly in older ages and in males. The
      prevalence of overweight was lower in the population with the systematic
      intervention team, and this was significant at the end of the paediatric age, 14
      years (P=.043). CONCLUSIONS: The overweight problem is so great that the measures
      aimed at their prevention are clearly beyond the scope of health professionals.
      However, interventions by health professionals can be effective in maintaining a
      healthy weight, if they are carried out on an ongoing basis.

PMID- 24139562
TI  - Differential effects of different vitamin D replacement strategies in patients
      with diabetes.
AB  - BACKGROUND: The optimal treatment regimen for correcting vitamin D insufficiency
      in diabetic patients has not been established. METHODS: Two hundred and forty
      four adult diabetic patients with vitamin D insufficiency were enrolled to
      receive: Ergocalciferol (D2) 50,000 IU daily over 10 days (500,000 IU) followed
      by Calcichew D3 (calcium carbonate/Cholecalciferol) BID (~24,000 IU
      cholecalciferol/month) (ECC) (n=53); Cholecalciferol (D3) 40,000 IU daily over 10
      days (400,000 IU) followed by Calcichew D3 BID (~24,000 IU cholecalciferol/month)
      (CCC) (n=94) or Cholecalciferol 40,000 IU daily over 10 days (400,000 IU)
      followed by Cholecalciferol 40,000 IU monthly (CC) (n=97). The 25(OH)D, HbA1c,
      lipids, blood pressure and eGFR were assessed at baseline and after a mean follow
      up of 8.0+/-4.0 months. RESULTS: Treatment increased 25(OH)D concentrations
      significantly in ECC (17.4+/-13.8 vs 29.9+/-9.6 ng/ml, P<0.0001), CCC (14.2+/-6.6
      vs 30.9+/-13.1 ng/ml, p<0.0001) and CC (13.5+/-8.4 vs 33.9+/-14.4 ng/ml,
      P<0.0001). The relative increase in 25(OH)D was significantly lower with ECC
      compared to CC (+14.6+/-12.2 vs +20.6+/-15.0, P=0.01) and the majority of
      subjects in the ECC group (63%) remained vitamin D deficient (25(OH)D <30 ng/ml)
      compared to CCC (46%) and CC (36%) (P=0.0005). CONCLUSION: This study
      demonstrates that relatively aggressive treatment regimens of both vitamin D2 and
      D3 increase 25(OH)D concentrations in diabetic patients, but the ability to raise
      25(OH)D status to 'sufficient' levels is inadequate in a large proportion of
      individuals.

PMID- 24139563
TI  - Concurrent bloodstream infections in infants with necrotizing enterocolitis.
AB  - OBJECTIVE: To determine the incidence, microbiology, risk factors, and outcomes
      related to bloodstream infections (BSIs) concurrent with the onset of necrotizing
      enterocolitis (NEC). STUDY DESIGN: We performed a retrospective review of all
      cases of NEC in a single center over 20 years. BSI was categorized as "NEC
      associated" if it occurred within 72 hours of the diagnosis of NEC and "post-NEC"
      if it occurred >72 hours afterwards. Demographics, hospital course data,
      microbiologic data, and outcomes were compared via univariate and multivariate
      analyses. RESULTS: NEC occurred in 410 infants with mean gestational age and
      birth weight of 29 weeks and 1290 g, respectively; 158 infants were diagnosed
      with at least one BSI; 69 (43.7%) with NEC-associated BSI, and 89 (56.3%) with
      post-NEC BSI. Two-thirds of NEC-associated BSI were due to gram-negative bacilli
      compared with 31.9% of post-NEC BSI (OR: 4.27; 95% CI: 2.02, 9.03) and 28.5% of
      all BSI in infants without NEC (OR: 5.02; 95% CI: 2.82, 8.96). Infants with NEC
      associated BSI had higher odds of requiring surgical intervention (aOR: 3.51; 95%
      CI: 1.98, 6.24) and death (aOR: 2.88; 95% CI: 1.39, 5.97) compared with those
      without BSI. CONCLUSIONS: BSI is a common, underappreciated complication of NEC
      occurring concurrent with the onset of disease and afterwards. The microbiologic
      etiology of NEC-associated BSI is different from post-NEC and late-onset BSI in
      infants without NEC with a predominance of gram-negative bacilli. Infants with
      NEC-associated BSI are significantly more likely to die than those with post-NEC
      BSI and NEC without BSI.

PMID- 24139565
TI  - Metabolic cost and mechanics of walking in women with fibromyalgia syndrome.
AB  - BACKGROUND: Fibromyalgia syndrome (FS) is characterized by the presence of
      widespread pain, fatigue, muscle weakness and reduced work capacity. Previous
      research has demonstrated that women with fibromyalgia have altered walking
      (gait) patterns, which may be a consequence of muscular pain. This altered gait
      is characterized by greater reliance on hip flexors rather than ankle plantar
      flexors and resembles gait patterns seen in normal individuals walking at higher
      speeds, suggesting that gait of individuals with fibromyalgia may be less
      efficient.This study compared rates of energy expenditure of 6 females with FS
      relative to 6 normal, age and weight matched controls, at various walking speeds
      on a motorized treadmill. Metabolic measurements including V02 (ml/kg/min),
      respirations, heart rate and calculated energy expenditures as well as the Borg
      Scale of Perceived Exertion scale ratings were determined at baseline and for 10
      min while walking at each of 2, 4 and 5 km/hour on 1% grade. Kinematic recordings
      of limb and body movements while treadmill walking and separate measurements of
      ground reaction forces while walking over ground were also determined. In
      addition, all subjects completed the RAND 36-Item Health Survey (1.0). FINDINGS:
      Gait analysis results were similar to previous reports of altered gait patterns
      in FS females. Despite noticeable differences in gait patterns, no significant
      differences (p > 0.05) existed between the FS and control subjects on any
      metabolic measures at any walking speed. Total number of steps taken was also
      similar between groups. Ratings on the Borg Scale of Perceived Exertion, the RAND
      and self-reported levels of pain indicated significantly greater (p < 0.05)
      perceived effort and pain in FS subjects relative to control subjects during
      walking and daily activities. CONCLUSIONS: The altered gait patterns and greater
      perceptions of effort and pain did not significantly increase the metabolic costs
      of walking in women with FS and hence, increased sensations of fatigue in FS
      women may not be related to alteration in metabolic cost of ambulation.

PMID- 24139566
TI  - Measuring media use in college students with and without human immunodeficiency
      virus infection.
AB  - INTRODUCTION: Media applications have shown promise for health education. The
      aims of this study were to develop and evaluate a media survey measure and
      compare media use among college students with and without human immunodeficiency
      virus (HIV) infection. METHODS: Using a cross-sectional, descriptive design, a
      convenience sample of college students (N = 53) were recruited. Psychometric
      testing of the media instrument was performed, and the tool was then used to
      compare media use among HIV-infected undergraduates (n = 15), other
      undergraduates (n = 23), and nursing students (n = 15). RESULTS: Psychometric
      testing of the media instrument demonstrated a high degree of reliability
      (intraclass correlation = .998; 95% confidence intervals = .997, .999). All
      respondents had computers with Internet access and cellular phones. Among HIV
      infected undergraduate students, 86.7% reported spending 5 minutes or more
      viewing television during the previous 24 hours outside of school and or work, in
      comparison with 34.8% of the other undergraduate students with no known chronic
      illness and 46.7% of the nursing students (p = .002 and .05, respectively).
      Preferred modes to access health information and communicate with health care
      providers for all respondents were the Internet (86.8%) and telephone (62.3%),
      respectively. DISCUSSION: Assessment of media use among adolescents and young
      adults will aid in planning for their health education needs.

PMID- 24139564
TI  - Alterations in brain structure and neurodevelopmental outcome in preterm infants
      hospitalized in different neonatal intensive care unit environments.
AB  - OBJECTIVE: To evaluate associations between neonatal intensive care unit (NICU)
      room type (open ward and private room) and medical outcomes; neurobehavior,
      electrophysiology, and brain structure at hospital discharge; and developmental
      outcomes at 2 years of age. STUDY DESIGN: In this prospective longitudinal cohort
      study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75
      bed level III NICU from 2007-2010. Upon admission, each participant was assigned
      to a bedspace in an open ward or private room within the same hospital, based on
      space and staffing availability, where they remained for the duration of
      hospitalization. The primary outcome was developmental performance at 2 years of
      age (n = 86 infants returned for testing, which was 83% of survivors) measured
      using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary
      outcomes were: (1) medical factors throughout the hospitalization; (2)
      neurobehavior; and (3) cerebral injury and maturation (determined by magnetic
      resonance imaging and electroencephalography). RESULTS: At term equivalent age,
      infants in private rooms were characterized by a diminution of normal hemispheric
      asymmetry and a trend toward having lower amplitude integrated
      electroencephalography cerebral maturation scores (P = .02; beta = -0.52 [CI 
      0.95, -0.10]). At age 2 years, infants from private rooms had lower language
      scores (P = .006; beta = -8.3 [CI -14.2, -2.4]) and a trend toward lower motor
      scores (P = .02; beta = -6.3 [CI -11.7, -0.99]), which persisted after adjustment
      for potential confounders. CONCLUSION: These findings raise concerns that
      highlight the need for further research into the potential adverse effects of
      different amounts of sensory exposure in the NICU environment.

PMID- 24139567
TI  - Functional status of elderly adults before and after interventions for critical
      limb ischemia.
AB  - OBJECTIVE: The impact of interventions for critical limb ischemia (CLI) on
      functional status in the elderly remains unclear. Open and endovascular
      procedures were evaluated. METHODS: Medicare inpatient claims were linked with
      nursing home assessment data to identify elective admissions for lower extremity
      procedures for CLI. A functional impairment score (0-28; higher scores indicating
      greater impairment) based on residents' need for assistance with self-care
      activities, walking, and locomotion was calculated before and after
      interventions. Hierarchical modeling determined the effect of the surgery on
      residents' function, controlling for comorbidity, cognition, and prehospital
      function. RESULTS: Three hundred fifty-two and 350 patients underwent open and
      endovascular procedures, respectively (rest pain, 84; ulceration, 351; gangrene,
      267). Hospitalization was associated with a significant worsening in function
      following both procedures. Disease severity was associated with the amount of
      initial decline but not with the rate of recovery (P > .35). Residents who
      received open surgery improved more quickly following hospital discharge (P =
      .011). CONCLUSIONS: In the frail elderly, open and endovascular procedures for
      CLI were associated with similar initial declines in functional status,
      suggesting that compared with open procedures, less invasive endovascular
      procedures were not associated with maintaining baseline function. In this select
      population, endovascular procedures for CLI were not associated with improved
      functional status over time compared with open. Six months posthospital, patients
      who received traditional open bypass had significantly better functional status
      than those who received endovascular procedures for all CLI diagnoses. Further
      analysis is required to assist stakeholders in performing procedures most likely
      to preserve functional status in the frail elderly and nursing home population.

PMID- 24139568
TI  - Late open conversion after failed endovascular aortic aneurysm repair.
AB  - OBJECTIVE: Endovascular aortic aneurysm repair (EVAR) is widely used for the
      treatment of abdominal aortic aneurysms. Complications secondary to EVAR are also
      treated with endovascular techniques. When this is not applicable, open surgical
      repair is mandatory. This study aims to present our experience in open surgical
      repair after failed EVAR. METHODS: Within the period from 2004 through 2013, 18
      patients (17 men; mean age, 73.9 years) were operated on because of EVAR failure
      due to persistent type II endoleak (n = 10), type I or III endoleak (n = 3),
      mixed-type endoleaks (n = 2), stent graft thrombosis (n = 2), and aortoenteric
      fistulae (n = 1). Stent grafts used for EVAR were Zenith (n = 8), Talent (n = 4),
      Excluder (n = 4), and Anaconda (n = 2). RESULTS: Mean time interval between EVAR
      and open conversion was 36 months (range, 2-120 months). Fifteen (83.3%)
      operations were elective, and three (16.7%) were urgent due to aneurysm rupture
      (n = 2) and aortoenteric fistula (n = 1). Six (33.3%) patients with type II
      endoleak were treated with simple ligation of the culprit vessels, without aortic
      clamping and stent graft explantation. In six (33.3%) patients, the stent graft
      was partially removed except from the segment attached to the proximal neck,
      while in five (27.8%) patients, complete removal of the stent graft was
      necessary. Finally, in one patient, with type III endoleak, a hybrid endovascular
      and open repair was performed. Clamping of the aorta was necessary in 12 (66.7%)
      patients (infrarenal, n = 10 or suprarenal, n = 2). Overall operative mortality
      was 5.6%. Postoperative complications included one abdominal wall defect
      requiring surgical revision and paroxysmal atrial fibrillation both in the same
      patient, and one case of pulmonary infection, requiring prolonged intubation and
      intensive care unit stay for 6 days. CONCLUSIONS: Late open conversion after
      failed EVAR remains challenging. Avoidance of aortic cross-clamping and if
      possible, partial or total preservation of the stent graft may improve outcomes
      in terms of operative mortality and morbidity. Elective operations seem to be
      associated with better outcomes, prompting thus for close follow-up of EVAR
      patients and early decision for conversion if other options are doubtful.

PMID- 24139569
TI  - Analytical and bioanalytical approaches to unravel the selenium-mercury
      antagonism: a review.
AB  - Mercury is a well-known risk to ecosystems and human health. Considering that no
      effective treatment is available to counteract mercury toxicity, the
      effectiveness of different trace elements, agents and nutrients with antioxidant
      properties to protect or reverse mercury toxicity is crucial. In this article we
      present the main analytical and bioanalytical strategies that have been used to
      study the potential of selenium as a protective agent against mercury-induced
      toxicity. We review the different seleno-species and routes of administration
      tested, and consider the analytical approaches used to evaluate the influence of
      selenium on the uptake and assimilation of mercury by model animals. In addition,
      we describe a variety of methods for toxicity assessment that have been used to
      elucidate the antagonism mercury-selenium, and critically review the main results
      obtained to date. Future potential research interests that could provide a
      clearer picture of this phenomenon are also presented. 

PMID- 24139570
TI  - Matrix enhancement effect: a blessing or a curse for gas chromatography?--A
      review.
AB  - The matrix enhancement effect in gas chromatography (GC) has been a problem for
      the last decade and results in unexpected high recovery. Most efforts, including
      the use of different types of injectors/matrix simplification procedures, and
      further clean-up associated with removing this effect has focused on equalizing
      the response of the standard in the solvent and matrix. However, after
      eliminating the matrix enhancement effect, the sensitivity of GC remained
      unchanged. But, GC sensitivity can be increased by utilizing this matrix effect
      originating from a matrix-matched standard. Very few studies have highlighted
      utilizing the matrix effect but have rather advocated eliminating it. Analyte
      protectants (3-ethoxy-1,2-propanediol, gulonolactone and sorbitol) have been
      introduced as an alternative for GC-mass spectroscopy (GC-MS) (not examined for
      other GC detectors), as they equalize the response without removing the matrix
      effect, and, hence, increase sensitivity. Versatile applications of analyte
      protectants are not observed in practice. The European guidelines recommend the
      use of matrix-matched standard calibration for residue measurements. As a result,
      numerous applications are available for matrix-matched standards that compensate
      for the matrix effect. Moreover, the matrices (among them pepper leaf matrix) act
      as a protectant for thermolabile analytes in some cases. A lower detection limit
      should be achieved to comply with the maximum residue limits. Therefore, the
      matrix enhancement effect, which is considered a problem, can play an important
      role in lowering the detection limit by increasing the transfer of analyte from
      the injection port to the detector. 

PMID- 24139571
TI  - Merits of random forests emerge in evaluation of chemometric classifiers by
      external validation.
AB  - Real-world applications will inevitably entail divergence between samples on
      which chemometric classifiers are trained and the unknowns requiring
      classification. This has long been recognized, but there is a shortage of
      empirical studies on which classifiers perform best in 'external validation'
      (EV), where the unknown samples are subject to sources of variation relative to
      the population used to train the classifier. Survey of 286 classification studies
      in analytical chemistry found only 6.6% that stated elements of variance between
      training and test samples. Instead, most tested classifiers using hold-outs or
      resampling (usually cross-validation) from the same population used in training.
      The present study evaluated a wide range of classifiers on NMR and mass spectra
      of plant and food materials, from four projects with different data properties
      (e.g., different numbers and prevalence of classes) and classification
      objectives. Use of cross-validation was found to be optimistic relative to EV on
      samples of different provenance to the training set (e.g., different genotypes,
      different growth conditions, different seasons of crop harvest). For classifier
      evaluations across the diverse tasks, we used ranks-based non-parametric
      comparisons, and permutation-based significance tests. Although latent variable
      methods (e.g., PLSDA) were used in 64% of the surveyed papers, they were among
      the less successful classifiers in EV, and orthogonal signal correction was
      counterproductive. Instead, the best EV performances were obtained with machine
      learning schemes that coped with the high dimensionality (914-1898 features).
      Random forests confirmed their resilience to high dimensionality, as best overall
      performers on the full data, despite being used in only 4.5% of the surveyed
      papers. Most other machine learning classifiers were improved by a feature
      selection filter (ReliefF), but still did not out-perform random forests. 

PMID- 24139572
TI  - A new approach to untargeted integration of high resolution liquid chromatography
      mass spectrometry data.
AB  - Because of its high sensitivity and specificity, hyphenated mass spectrometry has
      become the predominant method to detect and quantify metabolites present in bio
      samples relevant for all sorts of life science studies being executed. In
      contrast to targeted methods that are dedicated to specific features, global
      profiling acquisition methods allow new unspecific metabolites to be analyzed.
      The challenge with these so-called untargeted methods is the proper and automated
      extraction and integration of features that could be of relevance. We propose a
      new algorithm that enables untargeted integration of samples that are measured
      with high resolution liquid chromatography-mass spectrometry (LC-MS). In contrast
      to other approaches limited user interaction is needed allowing also less
      experienced users to integrate their data. The large amount of single features
      that are found within a sample is combined to a smaller list of, compound
      related, grouped feature-sets representative for that sample. These feature-sets
      allow for easier interpretation and identification and as important, easier
      matching over samples. We show that the automatic obtained integration results
      for a set of known target metabolites match those generated with vendor software
      but that at least 10 times more feature-sets are extracted as well. We
      demonstrate our approach using high resolution LC-MS data acquired for 128
      samples on a lipidomics platform. The data was also processed in a targeted
      manner (with a combination of automatic and manual integration) using vendor
      software for a set of 174 targets. As our untargeted extraction procedure is run
      per sample and per mass trace the implementation of it is scalable. Because of
      the generic approach, we envision that this data extraction lipids method will be
      used in a targeted as well as untargeted analysis of many different kinds of TOF
      MS data, even CE- and GC-MS data or MRM. The Matlab package is available for
      download on request and efforts are directed toward a user-friendly Windows
      executable. 

PMID- 24139573
TI  - A novel algorithm for linear multivariate calibration based on the mixed model of
      samples.
AB  - We present a novel algorithm for linear multivariate calibration that can
      generate good prediction results. This is accomplished by the idea of that
      testing samples are mixed by the calibration samples in proper proportion. The
      algorithm is based on the mixed model of samples and is therefore called MMS
      algorithm. With both theoretical support and analysis of two data sets, it is
      demonstrated that MMS algorithm produces lower prediction errors than partial
      least squares (PLS2) model, has similar prediction performance to PLS1. In the
      anti-interference test of background, MMS algorithm performs better than PLS2. At
      the condition of the lack of some component information, MMS algorithm shows
      better robustness than PLS2. 

PMID- 24139574
TI  - Conversion to isothiocyanates via dithiocarbamates for the determination of
      aromatic primary amines by headspace-solid phase microextraction and gas
      chromatography.
AB  - A novel and highly selective method has been developed for the determination of
      aromatic primary amines by their conversion to dithiocarbamates by reaction with
      carbon disulphide, and then to isothiocyanates, which are volatile, by heating in
      the presence of a heavy metal ion. Zinc(II) was selected owing to its low
      toxicity and optimum yield of isothiocyanates. The latter were sampled by
      headspace-solid phase microextraction (HS-SPME) on divinylbenzene-carboxen
      polydimethylsiloxane fibre, 50/30 MUm. The HS-SPME procedure was optimized to
      provide adequate limits of detection in the analysis of aromatic amines in their
      real samples by gas chromatography with mass spectrometry (GC-MS) or flame
      ionization detection (GC-FID). The method gave rectilinear calibration graph,
      correlation coefficient and limit of detection, respectively, over the range 0.08
      100 MUg L(-1), 0.9950-0.9990 and 25-240 ng L(-1) in gas chromatography-mass
      spectrometry, and 0.01-10 mg L(-1), 0.9910-0.9991 and 0.8-3.0 MUg L(-1) in gas
      chromatography-flame ionization detection. At two different levels, 10 and 40 MUg
      L(-1), the range of intra-day RSD was 3.7-8.5% (GC-MS) and 3.3-9.2% (GC-FID),
      respectively. The proposed method is simple and rapid, and has been applied to
      determine aromatic primary amines in the environmental waters, food samples of
      ice cream powder and soft drinks concentrate, and food colours. The intra-day RSD
      in the analysis of real samples by GC-MS was in the range 3.6-6.2%. The
      food/colour samples were found to contain elevated levels of aniline and 2
      toluidine.

PMID- 24139575
TI  - Flow methods in chiral analysis.
AB  - The methods used for the separation and analytical determination of individual
      isomers are based on interactions with substances exhibiting optical activity.
      The currently used methods for the analysis of optically active compounds are
      primarily high-performance separation methods, such as gas and liquid
      chromatography using chiral stationary phases or chiral selectors in the mobile
      phase, and highly efficient electromigration techniques, such as capillary
      electrophoresis using chiral selectors. Chemical sensors and biosensors may also
      be designed for the analysis of optically active compounds. As enantiomers of the
      same compound are characterised by almost identical physico-chemical properties,
      their differentiation/separation in one-step unit operation in steady-state or
      dynamic flow systems requires the use of highly effective chiral selectors.
      Examples of such determinations are reviewed in this paper, based on 105
      references. The greatest successes for isomer determination involve
      immunochemical interactions, enantioselectivity of the enzymatic biocatalytic
      processes, and interactions with ion-channel receptors or molecularly imprinted
      polymers. Conducting such processes under dynamic flow conditions may
      significantly enhance the differences in the kinetics of such processes, leading
      to greater differences in the signals recorded for enantiomers. Such
      determinations in flow conditions are effectively performed using surface-plasmon
      resonance and piezoelectric detections, as well as using common spectroscopic and
      electrochemical detections. 

PMID- 24139576
TI  - Detection of hexavalent chromium using gold/4-(2-mercaptoethyl) pyridinium
      surface enhanced Raman scattering-active capture matrices.
AB  - In this communication, the fabrication of SERS-active capture matrices for the
      detection of hexavalent chromium is described. The amine groups of amine-modified
      magnetic microparticles were used to immobilize gold colloidal particles. Once
      immobilized, the gold was reacted with 4-(2-mercaptoethyl) pyridinium (MEP)
      hydrochloride to form a self-assembled monolayer (SAM). The MEP SAM exhibits
      great selectivity for hexavalent chromium. It was shown that calibration curves
      could be generated by ratioing MEP peaks that increased in intensity upon
      complexation with chromate with a peak that did not change. Flow experiments,
      using Au/MEP capture matrices held in place by a magnet, showed instantaneous
      response to changes in chromate concentration. 

PMID- 24139577
TI  - Automatic polymerase chain reaction product detection system for food safety
      monitoring using zinc finger protein fused to luciferase.
AB  - An automatic polymerase chain reaction (PCR) product detection system for food
      safety monitoring using zinc finger (ZF) protein fused to luciferase was
      developed. ZF protein fused to luciferase specifically binds to target double
      stranded DNA sequence and has luciferase enzymatic activity. Therefore, PCR
      products that comprise ZF protein recognition sequence can be detected by
      measuring the luciferase activity of the fusion protein. We previously reported
      that PCR products from Legionella pneumophila and Escherichia coli (E. coli) O157
      genomic DNA were detected by Zif268, a natural ZF protein, fused to luciferase.
      In this study, Zif268-luciferase was applied to detect the presence of Salmonella
      and coliforms. Moreover, an artificial zinc finger protein (B2) fused to
      luciferase was constructed for a Norovirus detection system. In the luciferase
      activity detection assay, several bound/free separation process is required.
      Therefore, an analyzer that automatically performed the bound/free separation
      process was developed to detect PCR products using the ZF-luciferase fusion
      protein. By means of the automatic analyzer with ZF-luciferase fusion protein,
      target pathogenic genomes were specifically detected in the presence of other
      pathogenic genomes. Moreover, we succeeded in the detection of 10 copies of E.
      coli BL21 without extraction of genomic DNA by the automatic analyzer and E. coli
      was detected with a logarithmic dependency in the range of 1.0*10 to 1.0*10(6)
      copies. 

PMID- 24139578
TI  - Use of Cdse/ZnS quantum dots for sensitive detection and quantification of
      paraquat in water samples.
AB  - Based on the highly sensitive fluorescence change of water-soluble CdSe/ZnS core
      shell quantum dots (QD) by paraquat herbicide, a simple, rapid and reproducible
      methodology was developed to selectively determine paraquat (PQ) in water
      samples. The methodology enabled the use of simple pretreatment procedure based
      on the simple water solubilization of CdSe/ZnS QDs with hydrophilic
      heterobifunctional thiol ligands, such as 3-mercaptopropionic acid (3-MPA), using
      microwave irradiation. The resulting water-soluble QDs exhibit a strong
      fluorescence emission at 596 nm with a high and reproducible photostability. The
      proposed analytical method thus satisfies the need for a simple, sensible and
      rapid methodology to determine residues of paraquat in water samples, as required
      by the increasingly strict regulations for health protection introduced in recent
      years. The sensitivity of the method, expressed as detection limits, was as low
      as 3.0 ng L(-1). The lineal range was between 10-5*10(3) ng L(-1). RSD values in
      the range of 71-102% were obtained. The analytical applicability of proposed
      method was demonstrated by analyzing water samples from different procedence.

PMID- 24139579
TI  - Magnetic-particle-based, ultrasensitive chemiluminescence enzyme immunoassay for
      free prostate-specific antigen.
AB  - We report a magnetic-particle (MMP)-based chemiluminescence enzyme immunoassay
      (CLEIA) for free prostate-specific antigen (f-PSA) in human serum. In this
      method, the f-PSA is sandwiched between the anti-PSA antibody coated MMPs and
      alkaline phosphatase (ALP)-labeled anti-f-PSA antibody. The signal produced by
      the emitted photons from the chemiluminescent substrate (4-methoxy-4-(3
      phosphatephenyl)-spiro-(1,2-dioxetane-3,2'-adamantane)) is directly proportional
      to the amount of f-PSA in a sample. The present MMP-based assay can detect f-PSA
      in the range of 0.1-30 ng mL(-1) with the detection limit of 0.1 ng mL(-1). The
      linear detection range could match the concentration range within the "diagnostic
      gray zone" of serum f-PSA levels (4-10 ng mL(-1)). The detection limit was
      sufficient for measuring clinically relevant f-PSA levels (>4 ng mL(-1)).
      Furthermore, the method was highly selective; it was unaffected by cross-reaction
      with human glandular kallikrein-2, a kallikrein-like serine protease that is 80%
      similar to f-PSA. The proposed method was finally applied to determine f-PSA in
      40 samples of human sera. Results obtained using the method showed high
      correlation with those obtained using a commercially available microplate CLEIA
      kit (correlation coefficient, 0.9821). This strategy shows great potential
      application in the fabrication of diagnostic kits for determining f-PSA in serum.

PMID- 24139580
TI  - Infant mortality revisited.

PMID- 24139581
TI  - Hypokalemia and hyperkalemia in infants and children: pathophysiology and
      treatment.
AB  - Potassium is the second most abundant cation in the body. About 98% of potassium
      is intracellular and that is particularly in the skeletal muscle. Electrical
      disturbances associated with disorders of potassium homeostasis are a function of
      both the extracellular and intracellular potassium concentrations. Clinical
      disorders of potassium homeostasis occur with some regularity, especially in
      hospitalized patients receiving many medications. This article will review the
      pathophysiology of potassium homeostasis, symptoms, causes, and treatment of hypo
      and hyperkalemia. 

PMID- 24139582
TI  - Linking genome and immunity.

PMID- 24139583
TI  - Discovery of 2-methylpyridine-based biaryl amides as gamma-secretase modulators
      for the treatment of Alzheimer's disease.
AB  - gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments
      for Alzheimer's disease. They selectively lower pathogenic Abeta42 levels by
      shifting the enzyme cleavage sites without inhibiting gamma-secretase activity,
      possibly avoiding known adverse effects observed with complete inhibition of the
      enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM
      lead. Lead optimization studies identified compound 25 with improved cell
      potency, PKDM properties, and it lowered Abeta42 levels in the cerebrospinal
      fluid (CSF) of Sprague-Dawley rats following oral administration. Further
      optimization of 25 to improve cellular potency is described. 

PMID- 24139584
TI  - Identification and profiling of 3,5-dimethyl-isoxazole-4-carboxylic acid [2
      methyl-4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)phenyl] amide as histamine
      H(3) receptor antagonist for the treatment of depression.
AB  - Lead optimization guided by histamine H3 receptor (H3R) affinity and calculated
      physico-chemical properties enabled simultaneous improvement in potency and PK
      properties leading to the identification of a potent, selective, devoid of hERG
      issues, orally bioavailable, and CNS penetrable H3R antagonist/inverse agonist
      3h. The compound was active in forced-swimming tests suggesting its potential
      therapeutic utility as an anti-depressive agent. This Letter further includes its
      cardiovascular and neuropsychological/behavioral safety assessments. 

PMID- 24139585
TI  - Synthesis of 4"-O-desosaminyl clarithromycin derivatives and their anti-bacterial
      activities.
AB  - A series of new 4"-O-desosaminyl clarithromycin derivatives were designed and
      synthesized. The efficient synthesis routes of 6-deoxy-desosamine donors 8 and 11
      were developed and the methodology of glycosylation of clarithromycin 4"-OH with
      desosamine was studied. The activities of the target compounds were tested
      against a series of macrolide-sensitive and macrolide-resistant pathogens. Some
      of them showed activities against macrolide sensitive pathogens, and compounds 19
      and 22 displayed significant improvement of activities against sensitive
      pathogens and two strains of MRSE, which verified the importance of desosamine in
      the interaction of macrolide and its receptor, and offered valuable information
      of the SAR of macrolide 4"-OH derivatives. 

PMID- 24139586
TI  - Modified slide tracheoplasty in a newborn with bronchial and carinal stenosis.
AB  - Congenital tracheal stenosis (CTS) is a life-threatening condition that is
      associated with significant morbidity and mortality particularly when symptomatic
      presentation occurs in the newborn period. The most challenging form of CTS is
      long segment congenital tracheal stenosis (LSCTS) with compromise of the carina
      and main stem bronchi. We report the case of a newborn with severe distal
      tracheal stenosis with carinal and main stem bronchial involvement who was
      managed successfully with a modified slide and autologous rib graft
      tracheoplasty. The patient was discharged from hospital without ventilator
      support or oxygen requirement at 2 months of age. The details of this case and
      the description of the surgical procedure are presented and the related
      literature is reviewed. 

PMID- 24139587
TI  - Self-inserted foreign body and attention-deficit/hyperactivity disorder:
      evaluated by the Conners' Parent Rating Scales-Revised.
AB  - OBJECTIVES: We aimed to evaluate the relationship between attention
      deficit/hyperactivity disorder (ADHD) and self-inserted foreign bodies (SIFBs) in
      children by the Conners' Parent Rating Scales-Revised (CPRS-R). METHODS: Forty
      five children (31 males and 14 females) with self-inserted foreign body of
      ear/nose and 37 healthy children (22 males and 15 females) included into the
      study. They were all between 3 and 9 years old. The parents filled the socio
      demographic information form including age, gender, demographic data, previous
      medical history of the child and features of the family; and completed the
      Conners' Parent Rating Scales-Revised (CPRS-R) questionnaire. RESULTS: In the
      SIFB group (study), 55.6% of the children were not attending to the school, 31.1%
      of them were attending to the primary school and 13.3% of them were the pre
      school student. These rates were 37.8%, 32.4% and 29.7%, respectively, in the
      control group. The all CPRS-R subscale values (CG/I, H, ADHD-I, CGI-DI, DSMIV SS
      I, DSM-IV SS-HI and DSM-IV SS-T) were significantly higher in the study group
      than the control group. There was no significant correlation between gender of
      the children and CPRS-R subscales. Children with lower school success, and having
      previous psychiatric problems were related to higher CPRS-R values in all
      subscales. In older children, hyperactivity scores were lower; and in younger
      children and the children, not going to the school, hyperactivity scores were
      higher. CPRS-R scores decreased as the child grown. CONCLUSION: It was concluded
      that children with ADHD were more likely to have conditions that might damage
      himself/herself such as self-inserted foreign body or trauma than normal
      children. To avoid this condition, these families should closely observe the
      child; and the child should be provided to participate in activities such as
      group games and activities that contribute to the development of the child.
      Warning the children properly and close follow-up of the young children are
      required to prevent this unwanted condition.

PMID- 24139588
TI  - HPV and recurrent respiratory papillomatosis: a modern virus and a serious
      disease with controversial management.

PMID- 24139589
TI  - Delayed diagnosis and treatment of foreign body aspiration in China: the roles
      played by physician inexperience and lack of bronchoscopy facilities at local
      treatment centers.
AB  - OBJECTIVE: We examined if lack of on-site bronchoscopy facilities and the
      inexperience of initial treating physicians contributed to missed or delayed
      diagnosis of tracheobronchial foreign body aspiration (FBA) in pediatric patients
      presenting with respiratory distress. METHODS: The medical records of 340
      patients examined by bronchoscopy in our otolaryngology department from January
      2009 to August 2012 were reviewed. Age, gender, clinical history, findings on
      physical examination, facilities at the initial treatment site (bronchoscopy or
      not), bronchoscopic findings (type and location of the FB), and initial
      diagnosis, were examined in terms of the delay between initial treatment and
      bronchoscopy-based diagnosis of FBA. RESULTS: The vast majority of patients
      (324/340, 95.29%) were 3 years of age or younger and a foreign body was located
      in 309 (90.88%). Of these 340 cases, 261 had been referred from other facilities
      (76.76%) whereas 79 had come directly to our hospital (23.24%). The median delay
      between initial treatment and bronchoscopic diagnosis was significantly shorter
      in those treated initially in our institution compared to referrals (24 h [1 h to
      60 days] vs. 168 h [1 h to 366 days]; P < 0.01). The initial diagnosis was FBA in
      135/261 referral cases (51.72%), significantly lower than in cases first treated
      in our institution (69/79, 87.34%; P < 0.01). Foreign body aspiration was
      confirmed in 127/135 referral cases (94.07%) and 62/69 directly treated cases
      (89.86%) (chi(2) = 1.193, P > 0.05). Of the 126 referral cases diagnosed with
      other conditions before coming to our hospital, FBA was confirmed in 114.
      Complications were significantly less frequent in cases treated directly than in
      referrals (24/79, 30.38% vs. 155/261, 59.39%; P < 0.01). CONCLUSIONS: Local
      treatment facilities, most lacking bronchoscopy facilities and physicians who
      were trained to recognize FBA, misdiagnosed at least 44% of patients with
      respiratory distress and this led to significant delays in treatment. Greater
      regional access to bronchoscopy and improved training of primary care physicians
      will enhance diagnostic accuracy and reduce treatment delays.

PMID- 24139590
TI  - The financial impact of unrepaired cleft lip and palate in the Philippines.
AB  - OBJECTIVES: There are over 96 million people in the Philippines. Close to 77
      thousand persons in this country have orofacial clefting. We estimate nearly 64
      thousand are unrepaired. Unemployment and underemployment because of the
      communication disorders associated with unrepaired clefts will affect family
      income and hence tax revenues. The purpose of this study is to understand the
      financial impact of unrepaired cleft lip and/or palate on families and identify
      how that would translate to the Philippine government in tax revenues. METHODS:
      The incidence of orofacial cleft in the Philippines was estimated to be at least
      1 in 750 people, with only 16% anticipated to be repaired under current
      conditions. Assuming a 21% unemployment rate in subjects with untreated clefts,
      and a tax rate of 6-12.4%, projected lost personal income and federal tax revenue
      was calculated. RESULTS: In 2012 alone the financial impact on the families may
      be as much as $US 73-88 million in lost revenue from unemployment and
      underemployment. This would cost the government between $8.0 and $9.8 million
      dollars in lost tax revenue. Over a 20 year period at least $US 1.7 billion
      dollars in family income would be affected costing the government at least $US
      194 million in taxes. CONCLUSION: By appropriately caring for the cleft
      population tax revenues should increase substantially. The development of the
      infrastructure for surgical care of this problem would be costly but could be
      more than offset by revenues. Inattention to surgically correctable causes of
      communication disorders is not affordable.

PMID- 24139591
TI  - Incidence and predictors of malignancy in children with persistent cervical
      lymphadenopathy.
AB  - OBJECTIVE: The aim of this study was to analyze the clinical and histopathologic
      aspects of persistent cervical lymphadenopathies in children. METHODS: This
      retrospective study included 98 children who underwent surgical excision for
      persistently swollen cervical lymph nodes between 2001 and 2013. Lymph nodes
      greater than 1.5 cm that persisted for more than 4 weeks and were unresponsive to
      an initial antibiotic treatment were considered "persistent". The largest lymph
      node with an abnormal ultrasonographic appearance was selected for surgical
      biopsy. The patients were divided into 2 groups according to the histopathologic
      outcome: benign or malignant. RESULTS: No significant differences were found
      between the groups regarding the mean size and mean duration of the swollen
      cervical lymph nodes (p = 0.147 and p = 0.446, respectively). The area under the
      ROC curve was 0.567 (95% confidence interval = 0.463-0.667, p = 0.259) for lymph
      node size and 0.507 (95% confidence interval = 0.404-0.609, p = 0.909) for the
      duration of the cervical lymphadenopathy. There was no significant difference in
      the presence of B symptoms between the two groups (p = 0.519). No significant
      difference was found between benign and malignant groups regarding bilaterality
      (p=0.913). CONCLUSIONS: The findings of our study demonstrated that the size and
      duration of cervical lymphadenopathy, bilateral or unilateral involvement and the
      presence or absence of B symptoms are not indicators of malignancy. We found a
      high incidence of malignancy in pediatric cervical lymphadenopathy cases in
      contrast to other current studies.

PMID- 24139592
TI  - Pre-school hearing screening: profile of children from Ogbomoso, Nigeria.
AB  - OBJECTIVES: To carry out otoscopic and audiologic examinations amongst pre-school
      children in Ogbomoso, Nigeria in order to identify any cases of hearing loss and
      to intervene where possible. STUDY DESIGN AND SETTING: Prospective audiologic
      evaluations of children in Nursery I and II (pre-kindergarten and kindergarten)
      in both private and public primary schools were carried out. METHODS: One hundred
      and one children (202 ears) were screened using otoscopy and pure tone
      audiometry. RESULTS: The age ranged from 3.5 to 6 years, mean age was 4.8 years
      (S.D. = 0.835), with a male population of 55 and 46 females (M:F ratio, 1.2:1).
      Otoscopic findings revealed normal findings (106) 52.4%, impacted cerumen auris,
      44 (21.8%), otitis media with effusion, (28) 13.9%, perforated tympanic membrane,
      24 (11.9%) and giving an otoscopic pass rate of 52.4%. Screening audiometry, on
      the other hand, recorded a pass rate of 78.7%. After 6-8 weeks of otolaryngologic
      intervention, the otoscopic pass rate improved to 88.6%, while the pass rate for
      screening audiometry also improved to 93.6%. CONCLUSION/SIGNIFICANCE: From the
      study, an otoscopic pass rate of 52.9% and screening audiometry pass rate of
      78.7% increased to 88.6% and 93.6%, respectively, through basic otolaryngologic
      interventions. The key roles played in identifying ear diseases with or without
      hearing impairments with the use of clinical examination (otoscopy) and
      audiologic evaluation in the pre-school age children has been highlighted in the
      study. Unfortunately, these evaluations are not performed routinely in children
      enrolled in both private and public primary schools in Ogbomoso, Nigeria. We
      advocate that the routine otoscopic examinations with screening audiometry be
      made available in all primary schools, in order to facilitate early detection and
      prompt rehabilitation of children with ear diseases and hearing impairment.

PMID- 24139593
TI  - High expression of heparanase-2 is an independent prognostic parameter for
      favorable survival in gastric cancer patients.
AB  - AIM: Heparanase-2 expression has been suggested to up-regulate in several types
      of human cancers. However, the expression patterns of heparanase-2 in gastric
      cancer and its effect on prognosis of gastric cancer patients are unclear.
      METHODS: In this study, the methods of tissue microarray, immunohistochemistry
      (IHC), and western blot were used to investigate heparanase-2 expression in
      gastric cancer and the adjacent non-cancerous tissues. Heparanase-2 expression
      was analyzed by immunohistochemistry in 95 clinicopathologically characterized
      gastric cancer cases. In addition Fisher's exact test, Kaplan-Meier plots and Cox
      proportional hazards regression model were used to analyze the results. RESULTS:
      High expression of cytoplasmic heparanase-2 was observed in 70.5% (67/95) of
      gastric cancer, when compared with its normal counterpart. Overexpression of
      heparanase-2 was correlated with tumor size and differentiation (P<0.05). Further
      analysis showed that a significant correlation between high expression of
      heparanase-2 and favorable prognosis (P<0.05). In multivariate analysis, high
      expression of heparanase-2 was evaluated as an independent prognostic factor in
      gastric cancer (P<0.05). CONCLUSIONS: Our data suggest for the first time that
      the high expression of heparanase-2 is associated significantly with tumor growth
      and differentiation. Importantly, heparanase-2 may be a potential molecular
      marker for predicting prognosis of gastric cancer.

PMID- 24139594
TI  - Squamous anal cancer: patient characteristics and HPV type distribution.
AB  - BACKGROUND: Infection with high risk human papillomavirus (HPV) is strongly
      associated with anal cancer. However, detailed studies on HPV type distribution
      by gender and age are limited. METHODS: Retrospective study of 606 invasive anal
      cancers diagnosed between 1990 and 2005 in two large urban areas of the province
      of Quebec, Canada. Cases were identified from hospitalization registry. Patient
      characteristics were collected from medical files. Archived anal squamous cancer
      specimens were available from 96 patients and were tested for HPV DNA and typing.
      Variant analysis was performed on 16 consecutive and 24 non-consecutive HPV16
      positive samples to assess potential contamination during amplification. RESULTS:
      Among the 606 patients with anal cancers, 366 (60%) were women. Median age at
      diagnosis was 63 years. HPV was detected in 88/96 (92%) of cases. HPV16 was the
      most frequent type detected in 90% of HPV-positive specimens. Other types
      including 6, 11, 18, 33, 52, 53, 56, 58, 62 and 82 were also found. HPV 97 was
      not detected. HPV prevalence was associated with female gender and younger age.
      No contamination occurred during amplification as shown by the subset of 41 HPV16
      positive samples, as 37, 2 and 1 isolates were from the European, African and
      Asian lineages, respectively. The most frequent variants were G1 (n=22) and the
      prototype (n=12). CONCLUSIONS: Women with anal cancer are at higher risk for anal
      HPV infection, and HPV infection, especially HPV16, is strongly associated with
      squamous anal cancer. Therefore, HPV vaccine could potentially prevent the
      occurrence of anal cancer in both men and women.

PMID- 24139595
TI  - DTI-measured white matter abnormalities in adolescents with Conduct Disorder.
AB  - Emerging research suggests that antisocial behavior in youth is linked to
      abnormal brain white matter microstructure, but the extent of such anatomical
      connectivity abnormalities remain largely untested because previous Conduct
      Disorder (CD) studies typically have selectively focused on specific
      frontotemporal tracts. This study aimed to replicate and extend previous
      frontotemporal diffusion tensor imaging (DTI) findings to determine whether
      noncomorbid CD adolescents have white matter microstructural abnormalities in
      major white matter tracts across the whole brain. Seventeen CD-diagnosed
      adolescents recruited from the community were compared to a group of 24 non-CD
      youth which did not differ in average age (12-18) or gender proportion. Tract
      based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity
      (AD), and radial diffusivity (RD) measurements were compared between groups using
      FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p < .05.
      CD FA and AD deficits were widespread, but unrelated to gender, verbal ability,
      or CD age of onset. CD adolescents had significantly lower FA and AD values in
      frontal lobe and temporal lobe regions, including frontal lobe anterior/superior
      corona radiata, and inferior longitudinal and fronto-occipital fasciculi passing
      through the temporal lobe. The magnitude of several CD FA deficits was associated
      with number of CD symptoms. Because AD, but not RD, differed between study
      groups, abnormalities of axonal microstructure in CD rather than myelination are
      suggested. This study provides evidence that adolescent antisocial disorder is
      linked to abnormal white matter microstructure in more than just the uncinate
      fasciculus as identified in previous DTI studies, or frontotemporal brain
      structures as suggested by functional neuroimaging studies. Instead,
      neurobiological risk specific to antisociality in adolescence is linked to
      microstructural abnormality in numerous long-range white matter connections among
      many diverse different brain regions.

PMID- 24139596
TI  - Organizing national responses for rare blood disorders: the Italian experience
      with sickle cell disease in childhood.
AB  - BACKGROUND: Sickle cell disease (SCD) is the most frequent hemoglobinopathy
      worldwide but remains a rare blood disorder in most western countries.
      Recommendations for standard of care have been produced in the United States, the
      United Kingdom and France, where this disease is relatively frequent because of
      earlier immigration from Africa. These recommendations have changed the clinical
      course of SCD but can be difficult to apply in other contexts. The Italian
      Association of Pediatric Hematology Oncology (AIEOP) decided to develop a common
      national response to the rising number of SCD patients in Italy with the
      following objectives: 1) to create a national working group focused on pediatric
      SCD, and 2) to develop tailored guidelines for the management of SCD that could
      be accessed and practiced by those involved in the care of children with SCD in
      Italy. METHODS: Guidelines, adapted to the Italian social context and health
      system, were developed by 22 pediatric hematologists representing 54 AIEOP
      centers across Italy. The group met five times for a total of 128 hours in 22
      months; documents and opinions were circulated via web. RESULTS: Recommendations
      regarding the prevention and treatment of the most relevant complications of SCD
      in childhood adapted to the Italian context and health system were produced.
      CONCLUSIONS: Creating a network of physicians involved in the day-to-day care of
      children with SCD is feasible in a country where it remains rare. Providing
      hematologists, primary and secondary care physicians, and caregivers across the
      country with web-based guidelines for the management of SCD tailored to the
      Italian context is the first step in building a sustainable response to a rare
      but emerging childhood blood disorder and in implementing the World Health
      Organization's suggestion "to design (and) implement ... comprehensive national
      integrated programs for the prevention and management of SCD".

PMID- 24139597
TI  - Lessons from the one-carbon metabolism: passing it along to the next generation.
AB  - During development, a fetus and its placenta must respond to a changing maternal
      environment to ensure normal growth is achieved and survival is maintained. The
      mechanisms behind developmental programming involve complex interactions between
      epigenetic and physiological processes, which are not well understood.
      Importantly, when programming goes awry, it puts the fetus at risk for disease
      later in life and may, in some instances, affect subsequent generations via
      epigenetic processes including DNA methylation. The one-carbon metabolism, which
      includes the folate, methionine and choline pathways, provides methyl groups
      necessary for DNA methylation and a normal epigenetic landscape. Accordingly,
      disruptions in this pathway affect placental development and function leading to
      altered fetal programming. Remarkably, recent studies have revealed that abnormal
      folate metabolism causes transgenerational effects probably through epigenetic
      inheritance. The epigenetic mechanisms behind this phenomenon are not well
      understood but they have important implications for the influence of the
      metabolic environment on epigenetic stability and non-genetic inheritance of
      disease. Importantly, there are increasing concerns that assisted reproductive
      technologies cause aberrant epigenetic profiles in embryos leading to abnormal
      fetal programming. How the negative epigenetic consequences of assisted
      reproduction treatment affect subsequent generations requires further
      investigation.

PMID- 24139598
TI  - Conception through a looking glass: the paradox of IVF.
AB  - As we enter the fifth decade of human IVF, this technique presents a paradox. On
      the one hand, IVF has become more regular and ordinary, even a new norm of social
      life. On the other hand, it has arguably become, as Alice might have said,
      'curiouser and curiouser', with the development of its applications such as
      intracytoplasmic sperm injection, preimplantation genetic diagnosis and
      gestational surrogacy, as well as human embryonic stem cell derivation. Five
      million miracle babies later, in the midst of 'the age of biological control',
      IVF can be seen as the source of important changes in how reproductive biology is
      understood - socially, ethically, medically and in terms of basic science. This
      article reviews three decades of social scientific research into IVF and suggests
      that, while the passage of time may have allowed IVF to become more 'routine',
      the opposite is also true. With hindsight, some of the more radical changes to
      the understandings of parenthood, kinship, fertility and technology to which IVF
      has contributed can be appreciated. Learning from this paradox must be part of
      the legacy of IVF's first half-century if its future evolution is to be directed
      wisely, safely and conscientiously.

PMID- 24139600
TI  - The effect of sire predicted transmitting ability for production traits on
      fertility, survivability, and health of Holstein dairy cows.
AB  - The major objective of this study was to evaluate, using survival analysis and
      multivariable regression models, the relationship of sire predicted transmitting
      ability (PTA) for production traits with their daughters' milk production, fat,
      and protein percentage (PROPCT), reproductive performance, postpartum disease
      incidence, and survivability. Data were collected from six large commercial dairy
      farms, and data analysis included 22,205 cows. Information regarding each sire's
      genetic evaluation included the following: PTA for fat yield (FAT), fat
      percentage (FATPCT), milk yield (MILK), protein yield, and PROPCT. Sire PTA was
      categorized into quartiles to facilitate data analysis and interpretation.
      Retained placenta, metritis, displaced abomasum, and clinical mastitis were
      diagnosed and treated by farm personnel. The overall average daily milk
      production, milk fat and PROPCT during the first 10 months of lactation was
      higher for the cows in the highest quartile of sire PTA, and cows in the lowest
      quartile had lower averages. There was no significant association between sire
      PTA for production traits and first test day fat to protein ratio or the
      incidence of postpartum disease. Sire PTA for MILK, FATPCT, and PROPCT were
      significantly associated with the hazard of pregnancy. The median days from
      calving to conception were 159, 155, 170, and 181 days for cows in the sire PTA
      for MILK quartiles 1, 2, 3, and 4, respectively. Sire PTA for PROPCT and FATPCT
      were also significantly associated with the hazard of pregnancy. The median days
      from calving to conception were 175, 189, 152, and 145 for cows in the sire PTA
      for PROPCT groups 1, 2, 3, and 4, respectively. Additionally, cows in the highest
      quartile for sire PTA for FATPCT had the lowest median days from calving to
      conception (144 days) and cows in lowest quartile had the highest median interval
      (177 days). Sire PTA for FAT was the only sire PTA significantly associated with
      the hazard of death/culling. When compared with the cows in the highest sire PTA
      for FAT quartile cows in the first, second, and third quartiles were at 1.51,
      1.30, and 1.13 times higher hazard of death/culling, respectively. In conclusion,
      this study shows that high sire PTA for MILK and low sire PTA for milk fat and
      PROPCT are associated with decreased daughters' reproductive performance. Sire
      PTA for production traits were not found to be associated with postpartum disease
      incidence. 

PMID- 24139601
TI  - Glutathione and cysteine enhance porcine preimplantation embryo development in
      vitro after intracytoplasmic sperm injection.
AB  - Because intracytoplasmic sperm injection (ICSI) had been introduced to animal
      science, not only reproductive biology of domestic animals, but also medicine to
      treat infertility has been developed. This assisted reproductive technology is
      beneficial for generating transgenic animals, especially pigs, because polyspermy
      is the greatest hurdle in porcine IVF when researchers make highly qualified
      preimplantation embryos. However, ICSI-derived embryos expressed high level of
      reactive oxygen species (ROS), which are known to cause serious dysfunction
      during preimplantation development. The objective of this study was to
      investigate the developmental competence, ROS level, and apoptosis index when
      glutathione (GSH) or cysteine was supplemented into the in vitro culture medium
      for ICSI-derived porcine embryos. First, we evaluated the effect of different
      concentrations of GSH or cysteine on developmental ability of porcine ICSI
      derived embryos. The cleavage rate (79.6%) and the blastocyst formation rate
      (20.9%) were significantly improved in culture medium supplemented with 1 mmol/L
      GSH compared with other concentrations or no supplementation. Also, 1.71 mmol/L
      cysteine showed a significantly higher proportion of cleavage (80.7%) and
      blastocyst formation (22.5%) than other cysteine-supplemented groups. Next, we
      confirmed that intracellular ROS level was significantly reduced in the group of
      blastocysts cultured with GSH or cysteine after ICSI compared with the no
      supplementation group. Finally, we found that terminal uridine nick-end labeling
      index, fragmentation, and total apoptosis were significantly decreased and the
      total cell number was significantly increased in blastocysts when ICSI-derived
      embryos were cultured with supplementation of 1.71 mmol/L cysteine or 1 mmol/L
      GSH. Taken together, these results strongly indicate that GSH or cysteine can
      improve the developmental competence of porcine ICSI-derived embryos by reducing
      intracellular ROS level and the apoptosis index.

PMID- 24139602
TI  - Wilson's disease in pregnancy: case series and review of literature.
AB  - BACKGROUND: Wilson's disease is a rare, autosomal recessive inherited disorder
      characterized by impaired liver metabolism of copper leading to decreased biliary
      excretion and incorporation of ceruloplasmin levels mainly in the liver and
      brain. Untreated Wilson's disease has been shown to cause subfertility and even
      in cases where pregnancy occurs, it often results in spontaneous miscarriage.
      CASE PRESENTATIONS: We present four cases of successful pregnancy outcomes in
      three patients diagnosed with Wilson's disease along with the literature review.
      All the patients were managed with zinc sulphate without any postnatal
      complications. CONCLUSION: Patients with Wilson's disease receiving regular
      treatment who remain asymptomatic are usually able to conceive and achieve
      successful outcomes. However, these pregnancies should be considered high risk
      and merit regular surveillance.

PMID- 24139603
TI  - An assessment of opportunities and challenges for public sector involvement in
      the maternal health voucher program in Uganda.
AB  - BACKGROUND: Continued inequities in coverage, low quality of care, and high out
      of-pocket expenses for health services threaten attainment of Millennium
      Development Goals 4 and 5 in many sub-Saharan African countries. Existing health
      systems largely rely on input-based supply mechanisms that have a poor track
      record meeting the reproductive health needs of low-income and underserved
      segments of national populations. As a result, there is increased interest in and
      experimentation with results-based mechanisms like supply-side performance
      incentives to providers and demand-side vouchers that place purchasing power in
      the hands of low-income consumers to improve uptake of facility services and
      reduce the burden of out-of-pocket expenditures. This paper describes a
      reproductive health voucher program that contracts private facilities in Uganda
      and explores the policy and implementation issues associated with expansion of
      the program to include public sector facilities. METHODS: Data presented here
      describes the results of interviews of six district health officers and four
      health facility managers purposefully selected from seven districts with the
      voucher program in southwestern Uganda. Interviews were transcribed and organized
      thematically, barriers to seeking RH care were identified, and how to address the
      barriers in a context where voucher coverage is incomplete as well as
      opportunities and challenges for expanding the program by involving public sector
      facilities were investigated. RESULTS: The findings show that access to sexual
      and reproductive health services in southwestern Uganda is constrained by both
      facility and individual level factors which can be addressed by inclusion of the
      public facilities in the program. This will widen the geographical reach of
      facilities for potential clients, effectively addressing distance related
      barriers to access of health care services. Further, intensifying ongoing health
      education, continuous monitoring and evaluation, and integrating the voucher
      program with other services is likely to address some of the barriers. The public
      sector facilities were also seen as being well positioned to provide voucher
      services because of their countrywide reach, enhanced infrastructure, and
      referral networks. The voucher program also has the potential to address public
      sector constraints such as understaffing and supply shortages. CONCLUSIONS:
      Accrediting public facilities has the potential to increase voucher program
      coverage by reaching a wider pool of poor mothers, shortening distance to
      service, strengthening linkages between public and private sectors through public
      private partnerships and referral systems as well as ensuring the awareness and
      buy-in of policy makers, which is crucial for mobilization of resources to
      support the sustainability of the programs. Specifically, identifying policy
      champions and consulting with key policy sectors is key to the successful
      inclusion of the public sector into the voucher program.

PMID- 24139604
TI  - Spontaneous basophil responses in food-allergic children are transferable by
      plasma and are IgE-dependent.

PMID- 24139605
TI  - Advances in in vitro diagnostics in allergy, asthma, and immunology in 2012.
AB  - Laboratory tests play an increasing role in risk assessment, diagnostics, and
      disease monitoring. Great advances have been achieved lately, particularly in the
      field of clinical immunology and allergy. These include neonatal screening of
      immunodeficiencies and asthma biomarkers and investigation into the role of
      recombinant allergens in in vitro testing. The latter area has implications for
      the diagnostics of food allergy, pollen-induced allergies, asthma, and insect
      allergies.

PMID- 24139606
TI  - Methodological rigor and reporting of clinical practice guidelines in patients
      with allergic rhinitis: QuGAR study.
AB  - BACKGROUND: There are several clinical practice guidelines about the management
      of allergic rhinitis (AR) being used by clinicians. OBJECTIVE: We sought to
      assess the methodological rigor and transparency of reporting of clinical
      practice guidelines for the management of AR. METHODS: We systematically searched
      MEDLINE, the TRIP database, and professional society Web sites for all guidelines
      about the management of AR published in English after the year 2000. Four
      reviewers independently assessed the rigor of development and reporting of
      included guidelines using the Appraisal of Guidelines for Research and Evaluation
      II instrument. RESULTS: Our search revealed 432 records, of which 34 full-text
      articles were assessed for eligibility and 10 fulfilled inclusion criteria.
      Overall methodological rigor and reporting of guidelines varied from fulfilling
      most of the Appraisal of Guidelines for Research and Evaluation II criteria to
      almost none. Across all guidelines, the best reported domain was clarity of
      presentation, and the least rigorously addressed domain was applicability of
      guidelines. Agreement beyond chance among the 4 appraisers was fair. CONCLUSIONS:
      Guideline users should be aware of the difference in the rigor of development and
      quality of reporting of guidelines about the management of AR. They should choose
      higher-quality guidelines to use in their practice and teaching. For most
      reviewed guidelines, there is room for improvement, particularly in the domains
      of applicability and implementation.

PMID- 24139607
TI  - Prematurity, atopy, and childhood asthma in Puerto Ricans.
AB  - BACKGROUND: Puerto Rican children share a disproportionate burden of prematurity
      and asthma in the United States. Little is known about prematurity and childhood
      asthma in Puerto Rican subjects. OBJECTIVE: We sought to examine whether
      prematurity is associated with asthma in Puerto Rican children. METHODS: We
      performed a case-control study of 678 children aged 6 to 14 years with (n = 351)
      and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was
      defined by parental report for our primary analysis. In a secondary analysis, we
      only included children whose parents reported prematurity that required admission
      to the neonatal intensive care unit. Asthma was defined as physician-diagnosed
      asthma and wheeze in the prior year. We used logistic regression for analysis.
      All multivariate models were adjusted for age, sex, household income, atopy (>=1
      positive IgE level to common allergens), maternal history of asthma, and early
      life exposure to environmental tobacco smoke. RESULTS: In a multivariate analysis
      there was a significant interaction between prematurity and atopy on asthma (P =
      .006). In an analysis stratified by atopy, prematurity was associated with a
      nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio,
      4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant
      association between prematurity and asthma in nonatopic children. Similar results
      were obtained in our analysis of prematurity requiring admission to the neonatal
      intensive care unit and asthma. CONCLUSIONS: Our results suggest that atopy
      modifies the estimated effect of prematurity on asthma in Puerto Rican children.
      Prematurity might explain, in part, the high prevalence of atopic asthma in this
      ethnic group.

PMID- 24139608
TI  - IL-4 blocks TH1-polarizing/inflammatory cytokine gene expression during monocyte
      derived dendritic cell differentiation through histone hypoacetylation.
AB  - BACKGROUND: Whereas recent research has characterized the mechanism by which
      dendritic cells (DCs) induce T(H)1/T(H)17 responses, the functional
      specialization enabling DCs to polarize T(H)2 responses remains undefined.
      Because IL-4 is essential during T(H)2 responses not only by acting on CD4(+) T
      cells through the activation of GATA-3 but also by regulating IgE class
      switching, epithelial cell permeability, and muscle contractility, we
      hypothesized that IL-4 could also have a role in the conditioning of DCs during
      T(H)2 responses. OBJECTIVE: We sought to analyze whether IL-4 exerts an
      immunomodulatory function on DCs during their differentiation, leading to their
      functional specialization for the induction of T(H)2 responses. METHODS: Monocyte
      derived DCs (moDCs) conditioned by IL-4 during their differentiation (IL-4
      conditioned moDCs [IL-4-moDCs]) were analyzed for T(H)1-polarizing/inflammatory
      cytokine production in response to Toll-like receptor stimulation. The
      acetylation level of the promoters of the genes encoding these cytokines was
      analyzed by using chromatin immunoprecipitation. Gene expression profiling of IL
      4-moDCs was defined by using mouse genome microarrays. IL-4-moDCs were tested for
      their capacity to induce house dust mite-mediated allergic reactions. RESULTS:
      Our data suggest that IL-4 inhibits T(H)1-polarizing/inflammatory cytokine gene
      expression on IL-4-moDCs through the deacetylation of the promoters of these
      genes, leading to their transcriptional repression. Microarray analyses confirmed
      that IL-4 upregulated T(H)2-related genes as eosinophil-associated ribonucleases,
      eosinophil/basophil chemokines, and M2 genes. IL-4 licensed moDCs for the
      induction of T(H)2 responses, causing house dust mite-mediated allergic airway
      inflammation. CONCLUSION: This study describes a new role for IL-4 by
      demonstrating that moDCs are conditioned by IL-4 for the induction of T(H)2
      responses by blocking T(H)1-polarizing/inflammatory cytokine production through
      histone hypoacetylation and upregulating T(H)2-related genes.

PMID- 24139609
TI  - Intravenous immunoglobulin induces a functional silencing program similar to
      anergy in human B cells.
AB  - BACKGROUND: Chronic inflammatory and autoimmune diseases are largely due to
      inappropriate response of hyperactive or autoreactive B cells. These autoreactive
      B cells can evade central tolerance checkpoints and migrate to the periphery,
      where they would be silenced by anergy. Such anergic cells are characterized by B
      cell receptor (BCR) desensitization and altered downstream signaling. OBJECTIVE:
      We sought to determine whether intravenous immunoglobulin (IVIg) induces a
      nonresponsive state of B cells and to address the similarities of this mechanism
      to those described in anergy. METHODS: Human B cells were stimulated with anti
      IgM antibody, and effects of IVIg on several parameters, such as calcium release,
      tyrosine phosphorylation, BCR aggregation, BCR internalization, or
      transcriptional activity, were studied by using flow cytometry, confocal
      microscopy, Western blotting, and a quantitative PCR array. RESULTS: IVIg-treated
      B cells show defects in activating coreceptor expression, calcium signaling, and
      BCR aggregation on engagement by antigen. IVIg also induces suppression of
      phosphoinositide 3-kinase signaling, which plays a central role in determining B
      cell fate. All these events ultimately lead to profound modifications in gene
      expression, resulting in long-term functional but reversible silencing of IVIg
      treated B cells. CONCLUSION: Our findings provide insights into the effectiveness
      of IVIg in treating autoimmune or inflammatory pathologies associated with the
      loss of B-cell tolerance. Furthermore, these data provide a model to explore the
      complexity of positive versus negative selection in B cells.

PMID- 24139610
TI  - Pharmacological tools for the development of traditional Chinese medicine.
AB  - Pharmacology as a modern science was introduced in China approximately 150 years
      ago, and has been used since then to study traditional Chinese medicine (TCM).
      Pharmacology has experienced its own development over this time and continues to
      provide new tools for the study of TCM. In the present review, three models for
      the pharmacological study of TCM are considered: (i) chemistry-focused study;
      (ii) target-directed study; and (iii) systems-biology-based study. These
      approaches correspond to recent developments in pharmacology, and in particular
      to new tools available to the field. Representative achievements and the
      pharmacological tools used to study TCM are reviewed. Pharmacology has played,
      and will continue to play, an indispensable role in elucidating the chemical
      basis, biological targets, and mechanisms of action of TCM medicines, and in
      developing a scientific basis for the theory of TCM. 

PMID- 24139611
TI  - e-Phytovigilance for misleading herbal information.

PMID- 24139612
TI  - Toll-like receptors in atherosclerosis: a 'Pandora's box' of advances and
      controversies.
AB  - Seminal research over the past 20 years has revealed atherosclerosis to be a
      chronic inflammatory process that shares features with traditional inflammatory
      diseases including rheumatoid arthritis. More recently, emphasis has been placed
      on the role of innate immunity in the development and progression of
      atherosclerosis. In particular, pattern recognition receptors, including Toll
      like receptors (TLRs), have been the focus of much attention as modulators of
      atherogenesis. This review provides an update on the developments in this area of
      research in the past 2 years, with a specific focus on the current controversies
      and how these may affect the design of therapeutics. Specifically, we will
      address the recent evidence that TLRs elicit both protective and detrimental
      effects in atherosclerosis and the emerging observation that the outcome of TLR
      signaling is dependent on the agonist and responding cell type. 

PMID- 24139613
TI  - Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: a phase II,
      multi-institutional clinical trial.
AB  - OBJECTIVE: To determine the response rate, toxicity, and rate of complete
      resection after induction chemoradiotherapy for locally advanced thymic tumors,
      which were defined by specific radiographic criteria. METHODS: A single-arm,
      pilot trial was conducted at 4 institutions. Patients with thymoma or thymic
      carcinoma who met specific criteria on computed tomography were accrued.
      Induction therapy consisted of 2 cycles of cisplatin and etoposide combined with
      45 Gy of thoracic radiotherapy. Patients underwent computed tomography and
      positron emission tomography before and after induction therapy and then
      resection was attempted. Postoperative chemoradiotherapy was administered in
      selected patients. The primary endpoint was the pathologic response to induction
      therapy. The secondary endpoints were toxicity, surgical complications,
      radiographic response, and the rate of R0 resection. RESULTS: A total of 22
      patients were accrued during a 5-year period (1 patient withdrew before starting
      induction therapy). Of the 22 patients, 21 completed induction therapy, and 9
      (41%) experienced grade 3 or 4 toxicity. A total of 10 patients had a partial
      radiographic response and 11 had stable disease. Of the 21 patients, 17 (77%)
      underwent an R0 resection, 3 (14%) an R1 resection, and 1 (5%) underwent
      debulking. Eight patients sustained surgical complications (36%), and two
      patients (9%) died postoperatively. Of the 21 patients, 13 (62%) had either
      thymic carcinoma or B3 thymoma and 15 (71%) had either Masaoka stage III or IV
      disease. No patient had a complete pathologic response, but 5 specimens (24%) had
      <10% viable tumor. CONCLUSIONS: The present induction chemoradiotherapy protocol,
      which used specific computed tomography inclusion criteria to successfully select
      locally advanced thymic tumors, appeared to be tolerable and resulted in a high
      rate of complete surgical resection.

PMID- 24139614
TI  - End-diastolic flow reversal limits the efficacy of pediatric intra-aortic balloon
      pump counterpulsation.
AB  - BACKGROUND: Counterpulsation with an intra-aortic balloon pump (IABP) has not
      achieved the same success or clinical use in pediatric patients as in adults. In
      a pediatric animal model, IABP efficacy was investigated to determine whether
      IABP timing with a high-fidelity blood pressure signal may improve
      counterpulsation therapy versus a low-fidelity signal. METHODS: In Yorkshire
      piglets (n = 19; weight, 13.0 +/- 0.5 kg) with coronary ligation-induced acute
      ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the
      descending thoracic aorta. Inflation and deflation were timed with traditional
      criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer)
      blood pressure signals during 1:1 support. Aortic, carotid, and coronary
      hemodynamics were measured with pressure and flow transducers. Myocardial oxygen
      consumption was calculated from coronary sinus and arterial blood samples. Left
      ventricular myocardial blood flow and end-organ blood flow were measured with
      microspheres. RESULTS: Despite significant suprasystolic diastolic augmentation
      and afterload reduction at heart rates of 105 +/- 3 beats per minute, left
      ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial
      oxygen supply/demand relationship, cardiac output, and end-organ blood flow did
      not change. Statistically significant end-diastolic coronary, carotid, and aortic
      flow reversal occurred with IABP deflation. Inflation and deflation timed with a
      high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal
      or improve the myocardial oxygen supply/demand relationship. CONCLUSIONS:
      Systemic end-diastolic flow reversal limited counterpulsation efficacy in a
      pediatric model of acute left ventricular failure. Adjustment of IABP inflation
      and deflation timing with traditional criteria and a high-fidelity blood pressure
      waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic
      flow reversal may limit the efficacy of IABP counterpulsation therapy in
      pediatric patients with traditional timing criteria. Investigation of alternative
      deflation timing strategies is warranted.

PMID- 24139615
TI  - Historical perspectives of the American Association for Thoracic Surgery: Edward
      S. Welles (1891-1967).

PMID- 24139616
TI  - Discussion.

PMID- 24139617
TI  - Insights into the mechanism(s) of von Willebrand factor degradation during
      mechanical circulatory support.
AB  - OBJECTIVE: Left ventricular assist device support produces a bleeding diathesis.
      Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF
      metabolism in a preclinical model of short-term mechanical circulatory support.
      METHODS: In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the
      Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support
      was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid
      artery pressure and flow were measured to evaluate the hemodynamic changes near
      the anastomosis. At baseline and after <=2 weeks of support, platelet
      aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was
      performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF
      multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid
      arterial rings near the anastomosis were studied with immunohistochemical
      staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13
      production. Fluorescent resonance energy transfer was used to evaluate the
      enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured
      carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity,
      was measured using an enzyme-linked immunosorbent assay. RESULTS: During support,
      statistically significant (P < .05) changes in the carotid endothelium arterial
      hemodynamics were observed. The highest molecular weight vWF multimers were
      absent, and the vWF-ristocetin platelet aggregation pathway was significantly
      impaired. A modest but significant increase in plasma ADAMTS-13 protein and
      activity was observed. ADAMTS-13 decreased significantly in the carotid near the
      anastomosis but increased significantly in supernatant from cultured carotid
      arterial rings. The plasma interleukin-6 levels did not change significantly.
      CONCLUSIONS: Hemodynamic activation of vWF and increased plasma ADAMTS-13
      activity may have reduced high-molecular-weight vWF multimers and thereby
      impaired the vWF-platelet aggregation pathway. Additional delineation of these
      pathways may improve management of left ventricular assist device-associated
      bleeding.

PMID- 24139618
TI  - Cardiac electrographic and morphological changes following status epilepticus:
      effect of clonidine.
AB  - PURPOSE: Status epilepticus has been increasingly associated with cardiac injury
      in both clinical and animal studies. Our group has previously shown that
      excitotoxic seizure induction results in the formation of ischaemic myocardial
      infarcts and loss of cardiac haemodynamic function. We hypothesised that
      attenuation of cardiac sympathetic/parasympathetic balance with a central
      presynaptic alpha2 agonist, clonidine, can reduce the development of interictal
      ECG and ventricular morphological changes resulting from kainic acid (KA;
      10mg/kg) induced status epilepticus in a conscious rat model. METHODS: Using
      simultaneous ECG and electrocorticogram (ECoG) radiotelemetry, animals were
      randomised into saline controls, saline-pretreated KA and clonidine (100 MUg/kg,
      b.i.d.)-pretreated KA groups. Baseline ECG, ECoG and behavioural score recordings
      were acquired in conscious animals for 2h post-KA administration. RESULTS:
      Bradycardia and low level seizure activity occurred immediately following KA
      administration. As seizure activity (ECoG spiking and high level seizure
      behavioural scoring) progressively increased, tachycardia developed. Both QTc
      prolongation and T wave amplitude were transiently but significantly increased.
      Clonidine treatment attenuated seizure activity, increased the latency to onset
      of seizure behaviour and reduced seizure-induced changes in heart rate, QTc
      interval, and T wave amplitude. Histological examination of the ventricular
      myocardium revealed hypercontraction band necrosis, inflammatory cell
      infiltration, and oedema at 48 h post-KA. In contrast, clonidine-treatment in
      seizure animals preserved tissue integrity and structure. CONCLUSION: These
      results demonstrate that KA-induced seizures are associated with altered ECG
      activity and cardiac structural pathology. We suggest that pharmacological
      modulation of sympathetic/parasympathetic activity in status epilepticus provides
      a promising therapeutic approach to reduce seizure-induced cardiomyopathy.

PMID- 24139619
TI  - Neighborhood, family, and childhood and adolescent epilepsy: a nationwide
      epidemiological study from Sweden.
AB  - PURPOSE: To examine whether neighborhood deprivation increases the odds of
      hospital registration for childhood and adolescent epilepsy, after accounting for
      family- and individual-level sociodemographic characteristics. METHODS: An open
      cohort of all children aged 2-17 years was followed between January 1, 2000 and
      December 31, 2010. Children's residential addresses were geocoded and classified
      according to neighborhood deprivation. Data were analyzed by multilevel logistic
      regression, with family- and individual-level characteristics at the first level
      and level of neighborhood deprivation at the second level. RESULTS: During the
      study period, among a total of 1,020,766 children, 9309 (0.9%) were registered
      with childhood and adolescent epilepsy. Age-adjusted cumulative hospital rates of
      childhood and adolescent epilepsy increased with increasing neighborhood-level
      deprivation across all family- and individual-level sociodemographic categories.
      The odds ratio (OR) for hospital registration for childhood and adolescent
      epilepsy for those living in high-deprivation neighborhoods versus those living
      in low-deprivation neighborhoods was 1.15. High level deprivation remained
      significantly associated with higher odds of childhood and adolescent epilepsy
      after adjustment for family- and individual-level sociodemographic
      characteristics (OR=1.12, 95% CI=1.04-1.21, p=0.003). CONCLUSIONS: Our results
      suggest that neighborhood characteristics modestly affect the odds of hospital
      registration for childhood and adolescent epilepsy independently of family- and
      individual-level sociodemographic characteristics.

PMID- 24139620
TI  - Cystic echinococcosis in Mundari tribe-members of South Sudan.
AB  - Many neglected tropical diseases, including the zoonotic disease cystic
      echinococcosis (hydatidosis), are endemic to East Africa. However, their
      geographical distribution is heterogenous and incompletely characterized. The aim
      of this study was to determine if Mundari pastoralists harbor endemic human
      hydatidosis. The survey was conducted in cattle camps randomly selected from
      accessible sites provided by officials in Terekeka, South Sudan. Following
      informed consent, a questionnaire collected demographic data and hydatid exposure
      risk. A systematic sonographic abdominal exam was performed using General
      Electric's LOGIQ Book XP with a 3C-RS 2-5 MHz curvilinear transducer. Six hundred
      and ten individuals were screened from 13 camps. Four infections were identified,
      all in women. The prevalence of abdominal hydatid disease in the Mundari tribe
      members in cattle camps was 0.7% and all individuals reporting at least one high
      risk exposure to hydatid disease. Cystic echinococcosis is endemic among Mundari
      pastoralists; however, it would appear to be less endemic than in neighboring
      tribes. 

PMID- 24139621
TI  - [Epidemiology of otomycoses at the University Hospital of Yopougon (Abidjan-Ivory
      Coast)].
AB  - OBJECTIVE: Otomycosis is a fungal infection, which leads to a damage of the
      external auditory meatus. The disease is worldwide in distribution but is said to
      be more common in tropical countries. Though otomycosis presumably occurs
      frequently in Africa, reports on its incidence and etiology are rare from Cote
      d'Ivoire. The objective of this study was to evaluate the prevalence of the
      disease and to identify aetiological agents as well as the risk factors. MATERIAL
      AND METHODS: A cross-sectional study was carried out in the Otorhinolaryngology
      Department of the University Teaching Hospital of Yopougon from September 2007 to
      February 2008. For laboratory investigation, specimens were collected by means of
      a sterile swab. Samples were inoculated on Sabouraud's Dextrose Agar with and
      without antibiotics and incubated at 30 degrees C for a period of 1 to 2 weeks.
      Identification was performed by direct microscopic examination on Cotton Blue
      Mount preparation and slide culture examination was used for differentiation of
      morphology. Biotyping was performed using Carbohydrate Fermentation tests,
      Carbohydrate Assimilation Tests (galerie Api 20 CAux TM - Sanofi Pasteur), Germ
      tube Test, detection of chlamydospore formation on corn meal agar. RESULTS: A
      total of 110 patients (sex-ratio=1.2) with suspected cases of otomycosis were
      investigated. Itching, otalgia, and hypoacusis were the symptoms reported by the
      patients and the apparent signs were debris in the ear, scabs and inflammation of
      the external auditory meatus. Of these, 88 cases (80%) were confirmed
      specifically of mycotic etiology on the basis of positive culture with 92
      isolates consisting of yeasts (65.2%) and moulds (34.8%). The predominant
      etiological agents were Aspergillus flavus (28.4%), Candida guilliermondii
      (19.3%) and Candida parapsilosis (18.2%). The predisposing factors included
      previous otological pathology (P=0.010), frequent scratching of the external ear
      canal and use of ear drops (RR=3.47; IC 95%=1.3-9.27). CONCLUSION: This study
      revealed the great prevalence of otomycosis in Abidjan, some predisposing factors
      and the aetiological agents. Management of otomycosis must include mycological
      examination for diagnosis and information for changing behaviour patterns leading
      to infection.

PMID- 24139622
TI  - Antipsychotic switching in bipolar disorders: a systematic review.
AB  - With the increasingly widespread use of antipsychotics in bipolar disorder (BD),
      switching among these agents and between antipsychotics and mood stabilizers has
      become more common, in particular, since the introduction of the novel atypical
      antipsychotics with mood stabilizer properties. This systematic review aims to
      provide a comprehensive update of the current literature in BD about the
      switching of antipsychotics, among them and between them and mood stabilizers, in
      acute and maintenance treatment. We conducted a comprehensive, computerized
      literature search using terms related to antipsychotic switching in BD in the
      PubMed/Medline, PsycINFO, CINAHL database; the Cochrane Library and; the
      Clinicaltrials.gov web up to January 9th, 2013 according to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The
      search returned 4160 articles. After excluding duplications, reviews, case
      reports and studies that did not fulfil the selection criteria, 8 studies were
      included. Not only have few articles on antipsychotic switching been published
      but also recruitment in most studies included mixed samples of patients. In
      general, antipsychotic switching, regardless of the route of drug administration,
      was well tolerated and no interference was shown in antipsychotic effectiveness
      during the interchange of drugs. Metabolic improvement was perceived when the
      switch involved antipsychotics with a low metabolic risk profile. The evidence
      base for antipsychotic switching in BD is scant, and little controlled data is
      available. Switch from quetiapine to lithium and from risperidone to olanzapine
      has proven successful. Switching to antipsychotics with low metabolic risk had
      some positive impact on several safety measures. In stabilized patients, the
      plateau cross-taper switch may be preferred. 

PMID- 24139623
TI  - Parallelism as a novel marker for structural integrity of retinal layers in
      optical coherence tomographic images in eyes with epiretinal membrane.
AB  - PURPOSE: To propose a new parameter, "Parallelism," to evaluate retinal layer
      integrity on spectral-domain optical coherence tomography (SDOCT), and to
      investigate the association between parallelism and visual function in eyes with
      idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, observational
      evaluation of a diagnostic test. METHODS: We evaluated a consecutive series of 57
      eyes of 57 patients with ERM and 30 healthy eyes of 30 volunteers for whom M
      CHARTS testing and SDOCT were performed on the same day. OCT images were
      skeletonized, and the orientation of segmented lines in the image was termed
      "Parallelism" and was expressed as a value ranging from 0-1 and increasing as the
      retinal layers ran more parallel with each other. The relationships between
      parallelism and visual acuity and between parallelism and metamorphopsia score
      were evaluated. RESULTS: In normal eyes, parallelism was nearly homogeneous and
      varied slightly with the location. Parallelism in eyes with ERM was significantly
      lower than that in normal eyes. In the horizontal and vertical scans, parallelism
      was significantly correlated with visual acuity, horizontal metamorphopsia score,
      and vertical metamorphopsia score. Parallelism of the center (1 mm) in the
      horizontal scan was strongly correlated with horizontal metamorphopsia score (R =
      -0.632; P < .0001). Significant negative correlation was found between
      parallelism and retinal thickness both in horizontal and vertical scans.
      CONCLUSIONS: Parallelism was significantly lower in eyes with ERM than in normal
      eyes, and correlated strongly with metamorphopsia and visual acuity in eyes with
      ERM.

PMID- 24139624
TI  - Age at asthma onset and subsequent asthma outcomes among adults with active
      asthma.
AB  - INTRODUCTION: Little is known about the extent to which the age at which asthma
      first began influences respiratory health later in life. We conducted these
      analyses to examine the relationship between age at asthma onset and subsequent
      asthma-related outcomes. METHODS: We used data from 12,216 adults with asthma who
      participated in the 2010 Behavioral Risk Factor Surveillance System Asthma Call
      back Survey to describe the distribution of age at asthma onset. Linear
      regression was used to estimate associations of age at asthma onset with asthma
      related outcomes, including symptoms in the past 30 days and asthma-related
      emergency visits. RESULTS: Asthma onset before age 16 was reported by an
      estimated 42% of adults with active asthma, including 14% with onset at 5-9 years
      of age who reported experiencing any asthma symptoms on 21% of days in the past
      month. Compared to this group, the percentage of days in the past month with any
      asthma symptoms was 14.8% higher (95% confidence interval (CI): 5.4, 24.1) among
      those whose asthma onset occurred at <1 year. When age at onset occurred at 10
      years or older there was little change in the prevalence of asthma-related
      emergency visits across age at onset categories. CONCLUSION: Age at asthma onset
      may affect subsequent asthma-related outcomes.

PMID- 24139625
TI  - Remembering under stress: different roles of autonomic arousal and
      glucocorticoids in memory retrieval.
AB  - It is commonly assumed that stress impairs memory retrieval. Glucocorticoids,
      released with a delay of several minutes in response to stressful experiences,
      are thought to play a key role in the stress-induced retrieval impairment.
      Accordingly, most studies on the impact of stress on retrieval tested memory a
      considerable time after stressor exposure, when glucocorticoid levels were
      elevated. Here, we asked how stress affects memory when retrieval takes place
      under stress, that is, when stress is part of the retrieval situation and
      glucocorticoids are not yet increased at the time of testing. To contrast stress
      effects on ongoing and delayed memory retrieval, 72 participants learned first
      neutral and emotional material. Twenty-four hours later, half of the learned
      material was tested either in a stressful, oral examination-like testing
      situation or in a standard, non-stressful free recall test. Memory for the other
      half of the learned material was assessed 25 min after the first, stressful or
      non-stressful retention test. Significant increases in blood pressure and
      salivary cortisol confirmed the stress induction by the first, examination-like
      testing situation. Retrieval performance under stress was positively correlated
      with the blood pressure response to the stressor but unaffected by cortisol.
      Conversely, retrieval performance 25 min post stress was negatively correlated
      with the cortisol response to the stressor, particularly for emotional items.
      These results suggest that the same stressor may have opposite effects on ongoing
      and delayed memory retrieval, depending on the presence of autonomic arousal and
      glucocorticoids.

PMID- 24139626
TI  - Giving patients granular control of personal health information: using an ethics
      'Points to Consider' to inform informatics system designers.
AB  - OBJECTIVE: There are benefits and risks of giving patients more granular control
      of their personal health information in electronic health record (EHR) systems.
      When designing EHR systems and policies, informaticists and system developers
      must balance these benefits and risks. Ethical considerations should be an
      explicit part of this balancing. Our objective was to develop a structured ethics
      framework to accomplish this. METHODS: We reviewed existing literature on the
      ethical and policy issues, developed an ethics framework called a "Points to
      Consider" (P2C) document, and convened a national expert panel to review and
      critique the P2C. RESULTS: We developed the P2C to aid informaticists designing
      an advanced query tool for an electronic health record (EHR) system in
      Indianapolis. The P2C consists of six questions ("Points") that frame important
      ethical issues, apply accepted principles of bioethics and Fair Information
      Practices, comment on how questions might be answered, and address implications
      for patient care. DISCUSSION: The P2C is intended to clarify what is at stake
      when designers try to accommodate potentially competing ethical commitments and
      logistical realities. The P2C was developed to guide informaticists who were
      designing a query tool in an existing EHR that would permit patient granular
      control. While consideration of ethical issues is coming to the forefront of
      medical informatics design and development practices, more reflection is needed
      to facilitate optimal collaboration between designers and ethicists. This report
      contributes to that discussion.

PMID- 24139627
TI  - Spatial distribution of a population at risk: an important factor for
      understanding the recent rise in tick-borne diseases (Lyme borreliosis and tick
      borne encephalitis in the Czech Republic).
AB  - Recent rise in tick-borne diseases in many parts of Europe is a phenomenon in
      need of an explanation. We analyzed temporal trends in spatial distribution of a
      population at risk of Lyme borreliosis, tick-borne encephalitis, and as a
      control, also of a 'non-tick-borne disease' in the Czech Republic in 1997-2010.
      Analysis revealed that the population's exposure had been increasingly confined
      to the nearest surroundings of residences or in totally residential locations and
      that the incidence of the diseases depended in some causal way on how close to
      residences people exposed themselves to the risk. The rise in Lyme borreliosis
      and tick-borne encephalitis was solely due to infections acquired at or near
      patients' homes (<5 km), while the number of cases acquired further away was
      decreasing. The detected patterns in the data question some of the hypotheses
      which may be applicable in explaining the rise in disease incidences in the Czech
      Republic including the effect of climate change. Potentially causal factors are
      discussed.

PMID- 24139628
TI  - Presentation of intracranial arteriovenous malformations with symptomatic venous
      congestion.

PMID- 24139629
TI  - Clinical impact and therapeutic implications of cerebral microbleeds in patients
      on warfarin.

PMID- 24139630
TI  - Adenosine deaminase activity in cerebrospinal fluid.

PMID- 24139632
TI  - Virulence genes and antimicrobial susceptibility in Pasteurella multocida
      isolates from calves.
AB  - A total of 378 isolates of Pasteurella multocida from clinically healthy and
      diseased calves were characterised for their susceptibility to 9 antimicrobial
      agents and screened by PCR for the presence of antimicrobial resistance genes and
      22 genes virulence-associated, including capsule biosynthesis genes. Of the 378
      isolates, 102 (27.0%) were resistant to at least one of the 9 tested
      antimicrobial agents. Resistance to oxytetracycline (21.7%) was the most
      frequently observed phenotype among the isolates. The tet(H) gene were the
      primary determinant detected. The resistance rates for thiamphenicol, ampicillin,
      kanamycin and florfenicol were 13.2%, 5.8%, 9.0% and 0.5%, respectively.
      Cefazolin, ceftiofur, cefquinome and enrofloxacin were effective antimicrobial
      agents, with no resistant isolates emerging over the course of the investigation.
      Most isolates were identified as capsular type A, only 6.3% belonged to capsular
      type D and no other capsular type was identified. Four of the virulence
      associated genes (pfhA, tadD, tbpA and HAS) exhibited associations to the
      capsular type, and three (pfhA, tbpA and hgbB) were associated with the disease
      status of the animals. These virulence genes have been considered as
      epidemiological markers and are hypothesised to have a strong positive
      association with the outcome of disease in cattle. 

PMID- 24139633
TI  - Mast cell degranulation promotes ischemia-reperfusion injury in rat liver.
AB  - BACKGROUND: Mast cells (MCs) play a role in ischemia-reperfusion (I/R) injury in
      many organs. However, a recent study found that MCs are not involved in I/R
      injury in isolated rat livers that were perfused only for 1 h. The purpose of
      this study is to reevaluate the role of MCs in hepatic I/R injury in rat.
      MATERIALS AND METHODS: A warm hepatic I/R injury model of 1 h ischemia followed
      by 24 h of reperfusion was used. MC modulation was induced via cromolyn injection
      or a method called MC depletion using compound 48/80. The effects of MC
      modulation were evaluated by toluidine blue staining and assessment of mast cell
      tryptase in sera. The role of MCs in I/R injury was evaluated by hematoxylin and
      eosin staining graded by Suzuki criteria, alanine aminotransferase and aspartate
      aminotransferase levels in sera, and malondialdehyde levels in liver homogenates.
      RESULTS: First, MC degranulation peaked after 2 h of reperfusion and liver damage
      peaked after approximately 6 h of reperfusion. Second, a method called MC
      depletion previously used in the skin with repeated injections of compound 48/80
      worked similarly in the hepatic setting. Third, stabilization of MCs with
      cromolyn or depletion of MCs with compound 48/80 each decreased hepatic I/R
      injury. The most noticeable effects of cromolyn and compound 48/80 treatment were
      observed after approximately 6 h of reperfusion. CONCLUSIONS: MC degranulation
      promotes hepatic I/R injury in rats.

PMID- 24139631
TI  - Reassortants of the pandemic (H1N1) 2009 virus and establishment of a novel
      porcine H1N2 influenza virus, lineage in Germany.
AB  - The incursion of pandemic (H1N1) 2009 virus (pdmH1N1) into the German pig
      population was investigated in a serosurvey and by virological means between June
      2009 and December 2012. Analysis of 23,116 pig sera from a total of 2,666 herds
      revealed 224 herds that reacted with pdmH1N1 but not with the prevalent avian
      like H1N1 swine influenza virus. Sixty-six pdmH1N1 strains and their reassortant
      derivatives (pdmH1huN2, huH3pdmN1) have been collected since November 2009.
      Sequencing of three pdmH1N1, 20 pdmH1huN2 and one huH3pdmN1 strains with
      conventional and next generation sequencing techniques and subsequent
      phylogenetic analyses with available sequence data revealed the emergence of five
      distinct reassortant genotypes in Europe. The most frequent genotype emerged at
      least three times independently, one of which (Papenburg lineage) established a
      stable infection chain and became more prevalent in pigs than pdmH1N1 in Germany.

PMID- 24139634
TI  - The role of impaired esophageal and gastric motility in end-stage lung diseases
      and after lung transplantation.
AB  - Today, many questions persist regarding the causal relationship of
      gastroesophageal reflux disease (GERD) to promote aspiration and its potential to
      induce both pulmonary and allograft failure. Current hypotheses, which have
      identified GERD as a nonimmune risk factor in inducing pulmonary and allograft
      failure, center on the role of GERD-induced aspiration of gastroduodenal
      contents. Risk factors of GERD, such as impaired esophageal and gastric motility,
      may indirectly play a role in the aspiration process. In fact, although impaired
      esophageal and gastric motility is not independently a cause of lung
      deterioration or allograft failure, they may cause and or exacerbate GERD. This
      report seeks to review present research on impaired esophageal and gastric
      motility in end-stage lung disease to characterize prevalence, etiology,
      pathophysiology, and current treatment options within this special patient
      population. 

PMID- 24139635
TI  - Cone beam computed tomography for imaging orbital trauma--image quality and
      radiation dose compared with conventional multislice computed tomography.
AB  - We compared the image quality and radiation dose to the lens of the eye in
      patients with suspected orbital fractures who were imaged using cone beam
      computed tomography (CBCT) or conventional multislice computed tomography (CT).
      Although CBCT has a lower radiation dose than conventional CT, it is not known
      whether the image quality is comparable for diagnostic purposes. We identified
      fractures of the orbit (floor or roof, or both) in 6/10 patients who were scanned
      using CBCT and in 5/10 patients who were scanned using multislice CT (orbital
      floor and medial wall). Impingement of the rectus muscle on fracture lines was
      identified with both techniques, but retro-orbital haemorrhage was detected only
      on multislice CT. The mean radiation dose to the lens of the eye was 42% lower
      (range 23-53, SD 10) for CBCT than for multislice CT (p<0.001), and the effective
      dose (a measure of the risk of developing a radiation-induced cancer) was also
      significantly lower. CBCT can therefore be used to diagnose orbital fractures,
      and is associated with a significantly lower radiation dose than multislice CT.

PMID- 24139636
TI  - Results of a prospective study comparing the clinical efficacy of cryoablation of
      renal cell cancer followed by immediate partial nephrectomy.
AB  - PURPOSE: Evaluation if cryoablation of small renal tumours (RT) would facilitate
      the technique of laparoscopic partial nephrectomy (LPN) in a prospective study.
      PATIENTS AND METHODS: In a prospective non-randomised study between April 2007
      and October 2009, 16 patients with a mean age of 68 years (48-80 years) and a
      peripherally located RT were candidates for nephron-sparing surgery (5 open
      partial nephrectomy (OPN), 11 LPN). Cryoablation of RT was followed in the same
      session by open (K-OPN) and laparoscopic (K-LPN) partial nephrectomy.
      Perioperative and follow-up parameters were estimated. A matched-pair cohort of
      41 patients (20 OPN, 21 LPN) who underwent standard operations due to the same
      indication has been selected for retrospective comparison (controls). RESULTS:
      Mean age for K-OPN was 74 years (69-83) with mean blood loss 140 ml (50-200); for
      K-LPN: 66.6 years (48-80) with 100 ml (50-700). All procedures were completed
      successfully without conversions (K-LPN), transfusions or intra-operative
      complications. Compared to OPN/LPN, K-OPN and K-LPN were associated with a longer
      operative time (P < 0.05) and a comparable postoperative hospital stay. There
      were no early postoperative complications. Cryoablation has not affected the
      histopathological evaluation of tumours or resection margins. Histopathology
      showed cytologic changes suggesting fresh coagulative necrosis, glomerular
      vascular congestion and interstitial haemorrhages following cryotherapy. One
      patient (K-LPN) developed a pararenal abscess necessitating puncture after 7
      weeks. The follow-up (9-42 months) was uneventful. CONCLUSIONS: The current study
      shows that K-LPN is feasible without increasing procedure morbidity or
      compromising surgical and oncological outcomes. It adds no advantage to tumour
      excision. Pathological findings document early cryoablation effects but viable
      tissue.

PMID- 24139637
TI  - GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients.
AB  - BACKGROUND: Mutations in PMM2 impair phosphomannomutase-2 activity and cause the
      most frequent congenital disorder of glycosylation, PMM2-CDG. Mannose-1
      phosphate, that is deficient in this disorder, is also implicated in the
      biosynthesis of glycosylphosphatidyl inositol (GPI) anchors. OBJECTIVE: To
      evaluate whether GPI-anchor and GPI-anchored proteins are defective in PMM2-CDG
      patients. METHODS: The expression of GPI-anchor and seven GPI-anchored proteins
      was evaluated by flow cytometry in different cell types from twelve PMM2-CDG
      patients. Additionally, neutrophil CD16 and plasma hepatic proteins were studied
      by Western blot. Transferrin glycoforms were evaluated by HPLC. RESULTS: Patients
      and controls had similar surface expression of GPI-anchor and most GPI-anchored
      proteins. Nevertheless, patients displayed a significantly diminished binding of
      two anti-CD16 antibodies (3G8 and KD1) to neutrophils and also of anti-CD14
      (61D3) to monocytes. Interestingly, CD16 immunostaining and asialotransferrin
      levels significantly correlated with patients' age. Analysis by flow cytometry of
      CD14 with MPhiP9, and CD16 expression in neutrophils by Western blot using H-80
      ruled out deficiencies of these antigens. CONCLUSIONS: PMM2 mutations do not
      impair GPI-anchor or GPI-anchored protein expression. However, the glycosylation
      anomalies caused by PMM2 mutations might affect the immunoreactivity of
      monoclonal antibodies and lead to incorrect conclusions about the expression of
      different proteins, including GPI-anchored proteins. Neutrophils and monocytes
      are sensitive to PMM2 mutations, leading to abnormal glycosylation in immune
      receptors, which might potentially affect their affinity to their ligands, and
      contribute to infection. This study also confirms less severe hypoglycosylation
      defects in older PMM2-CDG patients.

PMID- 24139638
TI  - Sexual behaviour among users of antiretroviral pre-exposure prophylaxis.

PMID- 24139639
TI  - Sexual behaviour of heterosexual men and women receiving antiretroviral pre
      exposure prophylaxis for HIV prevention: a longitudinal analysis.
AB  - BACKGROUND: Scarce data are available to assess sexual behaviour of individuals
      using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased
      sexual risk taking by individuals using effective HIV prevention strategies, like
      pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied
      whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in
      HIV-serodiscordant couples was associated with increased sexual risk behaviour.
      METHODS: We undertook a longitudinal analysis of data from the Partners PrEP
      Study, a double-blind, randomised, placebo-controlled trial of daily oral pre
      exposure prophylaxis among HIV-uninfected partners of heterosexual HIV
      serodiscordant couples (n=3163, >=18 years of age). Efficacy for HIV prevention
      was publicly reported in July 2011, and participants continued monthly follow-up
      thereafter. We used regression analyses to compare the frequency of sex
      unprotected by a condom-during the 12 months after compared with the 12 months
      before July 2011, to assess whether knowledge of pre-exposure prophylaxis
      efficacy for HIV prevention caused increased sexual risk behaviour. RESULTS: We
      analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male).
      The average frequency of unprotected sex with the HIV-infected study partner was
      59 per 100 person-months before unmasking versus 53 after unmasking; we recorded
      no immediate change (p=0.66) or change over time (p=0.25) after July, 2011. We
      identified a significant increase in unprotected sex with outside partners after
      July, 2011, but the effect was small (average of 6.8 unprotected sex acts per
      year vs 6.2 acts in a predicted counterfactual scenario had patients remained
      masked, p=0.04). Compared with before July, 2011, we noted no significant
      increase in incident sexually transmitted infections or pregnancy after July,
      2011. INTERPRETATION: Pre-exposure prophylaxis, provided as part of a
      comprehensive prevention package, might not result in substantial changes in risk
      taking sexual behaviour by heterosexual couples. FUNDING: The Bill & Melinda
      Gates Foundation and the US National Institute of Mental Health.

PMID- 24139640
TI  - Retraction: Association of body weight and physical activity with blood pressure
      in a rural population in the Dikgale village of Limpopo Province in South Africa.

PMID- 24139642
TI  - Dominance patterns in macroalgal and phytoplankton biomass under different
      nutrient loads in subtropical coastal lagoons of the SE Gulf of California.
AB  - Nine macroalgal blooms were studied in five coastal lagoons of the SE Gulf of
      California. The nutrient loads from point and diffuse sources were estimated in
      the proximity of the macroalgal blooms. Chlorophyll a and macroalgal biomass were
      measured during the dry, rainy and cold seasons. Shrimp farms were the main point
      source of nitrogen and phosphorus loads for the lagoons. High biomasses were
      found during the dry season for phytoplankton at site 6 (791.7+/-34.6 mg m(-2))
      and during the rainy season for macroalgae at site 4 (296.0+/-82.4 g m(-2)).
      Depending on the season, the phytoplankton biomass ranged between 40.0 and 791.7
      mg m(-2) and the macroalgal biomass between 1 and 296.0 g m(-2). The bulk biomass
      (phytoplankton+macroalgal) displayed the same tendency as the nutrient loads
      entering the coastal lagoons. Phytoplankton and macroalgal biomass presented a
      significant correlation with the atomic N:P ratio.

PMID- 24139643
TI  - Temporal variability and climatology of hydrodynamic, water property and water
      quality parameters in the West Johor Strait of Singapore.
AB  - The study presents a baseline variability and climatology study of measured
      hydrodynamic, water properties and some water quality parameters of West Johor
      Strait, Singapore at hourly-to-seasonal scales to uncover their dependency and
      correlation to one or more drivers. The considered parameters include, but not
      limited by sea surface elevation, current magnitude and direction, solar
      radiation and air temperature, water temperature, salinity, chlorophyll-a and
      turbidity. FFT (Fast Fourier Transform) analysis is carried out for the
      parameters to delineate relative effect of tidal and weather drivers. The group
      and individual correlations between the parameters are obtained by principal
      component analysis (PCA) and cross-correlation (CC) technique, respectively. The
      CC technique also identifies the dependency and time lag between driving natural
      forces and dependent water property and water quality parameters. The temporal
      variability and climatology of the driving forces and the dependent parameters
      are established at the hourly, daily, fortnightly and seasonal scales. 

PMID- 24139641
TI  - Modulation of neuronal activity by phosphorylation of the K-Cl cotransporter
      KCC2.
AB  - The K-Cl cotransporter KCC2 establishes the low intraneuronal Cl- levels required
      for the hyperpolarizing inhibitory postsynaptic potentials mediated by ionotropic
      gamma-aminobutyric acid receptors (GABAARs) and glycine receptors (GlyRs).
      Decreased KCC2-mediated Cl- extrusion and impaired hyperpolarizing GABAAR- and/or
      GlyR-mediated currents have been implicated in epilepsy, neuropathic pain, and
      spasticity. Recent evidence suggests that the intrinsic ion transport rate, cell
      surface stability, and plasmalemmal trafficking of KCC2 are rapidly and
      reversibly modulated by the (de)phosphorylation of critical serine, threonine,
      and tyrosine residues in the C terminus of this protein. Alterations in KCC2
      phosphorylation have been associated with impaired KCC2 function in several
      neurological diseases. Targeting KCC2 phosphorylation directly or indirectly via
      upstream regulatory kinases might be a novel strategy to modulate GABA- and/or
      glycinergic signaling for therapeutic benefit.

PMID- 24139644
TI  - The combined use of the PLHC-1 cell line and the recombinant yeast assay to
      assess the environmental quality of estuarine and coastal sediments.
AB  - Sediment contamination poses a potential risk for both ecosystems and human
      health. Risk assessment is troublesome as sediments contain complex mixtures of
      toxicants, and traditional chemical analyses can neither provide information
      about potential hazards to organisms nor identify and measure all present
      contaminants. This work combines the use of the PLHC-1 cell line and the
      recombinant yeast assay (RYA) to assess the environmental quality of estuarine
      and coastal sediments. The application of multiple endpoints (cytotoxicity,
      generation of oxidative stress, presence of CYP1A inducing agents, micronucleus
      formation and estrogenicity) revealed that the organic extracts of those
      sediments affected by industrial activities or collected near harbours and
      untreated urban discharges showed significant cytotoxicity, micronuclei and CYP1A
      induction. The study highlights the usefulness of the applied bioassays to
      identify those sediments that could pose risk to aquatic organisms and that
      require further action to improve their environmental quality. 

PMID- 24139645
TI  - Kinetics of the PO4-P adsorption onto soils and sediments from the Mondego
      estuary (Portugal).
AB  - In order to assess the status of a North Atlantic Ocean Ecoregion (Mondego
      system, Portugal) after the implementation of a management programme, a study on
      PO4-P sorption was carried out. Considering that sorption velocity markedly
      determines the systems promptness to phosphorus external loading, the kinetics of
      the sorption of PO4-P onto estuarine sediments and the upstream agricultural
      soils was studied. The pseudo-second order kinetic equation gave an appropriate
      description of PO4-P sorption onto these soils and sediments, allowing for a
      quantitative comparison. For soils, the kinetic constants (k2*, MUg(-1) g h(-1))
      ranged between 0.007 and 0.017 MUg(-1) g h(-1) while, in the case of sediments
      these ranged between 0.008 and 0.012 MUg(-1) g h(-1). Results showed that the
      reduction of water residence time after the management action was relevant for
      the system status, affecting its reaction capacity to phosphorus loading.

PMID- 24139646
TI  - Influence of an intensive agricultural drainage basin on the seasonal
      distribution of organic pollutants in seawater from a Mediterranean coastal
      lagoon (Mar Menor, SE Spain).
AB  - The seasonal distribution of polycyclic aromatic hydrocarbons, polychlorinated
      biphenyls, organochlorine pesticides, organophosphorus pesticides, triazines and
      other organic pollutants in surface seawater from the Mar Menor lagoon (SE Spain)
      was characterized from spring 2009 to winter 2010 by stir bar sorptive extraction
      and thermal desorption followed by capillary gas chromatography coupled to mass
      spectrometry (SBSE-GC-MS). The most ubiquitous pollutants were chlorpyrifos,
      chlortal-dimethyl, terbuthylazine, naphthalene and propyzamide throughout the
      year. Insecticides and herbicides were predominant in summer and spring, and
      fungicides were more abundant in autumn and winter. Chlorpyrifos was predominant
      in autumn and spring; herbicides (propyzamide, terbuthylazine and terbuthylazine
      desethyl) in autumn and fungicides (flutolanil, boscalid, cyprodinil) in autumn
      and winter. The highest concentrations for the majority of pollutants were
      detected in autumn as consequence of air and surface/ground water inputs, and
      above all of desorption from terrigenous materials deposited in sediments by two
      intense flash flood events (September 2009). 

PMID- 24139647
TI  - Baseline of the butyltin distribution in surface sediments (0-20 cm) of the Elbe
      estuary (Germany, 2011).
AB  - The concentrations of the butyltin (BT) species tributyltin (TBT), dibutyltin
      (DBT), and monobutyltin (MBT) were measured in the surface sediments (0-20 cm) at
      29 sites of the Elbe estuary in 2011. TBT values ranged from 'undetectable' to 41
      ng Sn g(-1) dry weight (d.w.) with the two highest values measured in the inner
      section of the estuary near the port of Hamburg (32 and 41 ng Sn g(-1) d.w.).
      TBT, DBT, and MBT showed significant decreases towards the estuarine mouth
      (Spearman's rho -0.660, -0.685, and -0.583, respectively, p<0.001). The
      degradation of TBT, assessed by the BT degradation index (BDI), showed a rising
      trend from the port of Hamburg towards the mouth of the estuary, though not a
      significant one (Spearman's correlation, p=0.066). Annual sedimentation rates did
      not show any significant correlations (Spearman's correlation) to BT pollution or
      to the butyltin degradation index (BDI).

PMID- 24139648
TI  - Concentration of organic sun-blocking agents in seawater of beaches and coral
      reefs of Okinawa Island, Japan.
AB  - The concentration of UV filters (UVFs) and UV light stabilizers (UVLSs) were
      measured in seawater and river water collected from sites at four beaches, two
      reefs, and one river on Okinawa Island, Japan. UVFs and/or UVLSs of 8-10 types
      were detected in beaches samples and 6-9 types were detected in reef samples. The
      total UVF concentrations at the beach sites were highest either in July or August
      with a maximum of 1.4 MUg L(-1). The concentrations at the reef sites did not
      show peaks in summer and the maximum values were close to 10 ng L(-1). The
      detected UVF profiles reflected the ingredients of sunscreens used in each
      region. The highest UVLS concentrations at the reefs were observed not only in
      summer but also in June and September. The UVLS concentrations at the reefs were
      similar to or even higher than that at the beaches or in the river.

PMID- 24139649
TI  - Foreword.

PMID- 24139650
TI  - The XXIV Ottorino Rossi Award. Henry Markram.

PMID- 24139651
TI  - Seven challenges for neuroscience.
AB  - Although twenty-first century neuroscience is a major scientific enterprise,
      advances in basic research have not yet translated into benefits for society. In
      this paper, I outline seven fundamental challenges that need to be overcome.
      First, neuroscience has to become "big science" - we need big teams with the
      resources and competences to tackle the big problems. Second, we need to create
      interlinked sets of data providing a complete picture of single areas of the
      brain at their different levels of organization with "rungs" linking the
      descriptions for humans and other species. Such "data ladders" will help us to
      meet the third challenge - the development of efficient predictive tools,
      enabling us to drastically increase the information we can extract from expensive
      experiments. The fourth challenge goes one step further: we have to develop novel
      hardware and software sufficiently powerful to simulate the brain. In the future,
      supercomputer-based brain simulation will enable us to make in silico
      manipulations and recordings, which are currently completely impossible in the
      lab. The fifth and sixth challenges are translational. On the one hand we need to
      develop new ways of classifying and simulating brain disease, leading to better
      diagnosis and more effective drug discovery. On the other, we have to exploit our
      knowledge to build new brain-inspired technologies, with potentially huge
      benefits for industry and for society. This leads to the seventh challenge.
      Neuroscience can indeed deliver huge benefits but we have to be aware of
      widespread social concern about our work. We need to recognize the fears that
      exist, lay them to rest, and actively build public support for neuroscience
      research. We have to set goals for ourselves that the public can recognize and
      share. And then we have to deliver on our promises. Only in this way, will we
      receive the support and funding we need. 

PMID- 24139652
TI  - Realistic modeling of neurons and networks: towards brain simulation.
AB  - Realistic modeling is a new advanced methodology for investigating brain
      functions. Realistic modeling is based on a detailed biophysical description of
      neurons and synapses, which can be integrated into microcircuits. The latter can,
      in turn, be further integrated to form large-scale brain networks and eventually
      to reconstruct complex brain systems. Here we provide a review of the realistic
      simulation strategy and use the cerebellar network as an example. This network
      has been carefully investigated at molecular and cellular level and has been the
      object of intense theoretical investigation. The cerebellum is thought to lie at
      the core of the forward controller operations of the brain and to implement
      timing and sensory prediction functions. The cerebellum is well described and
      provides a challenging field in which one of the most advanced realistic
      microcircuit models has been generated. We illustrate how these models can be
      elaborated and embedded into robotic control systems to gain insight into how the
      cellular properties of cerebellar neurons emerge in integrated behaviors.
      Realistic network modeling opens up new perspectives for the investigation of
      brain pathologies and for the neurorobotic field. 

PMID- 24139653
TI  - The connectomics challenge.
AB  - One of the most fascinating challenges in neuroscience is the reconstruction of
      the connectivity map of the brain. Recent years have seen a rapid expansion in
      the field of connectomics, whose aim is to trace this map and understand its
      relationship with neural computation. Many different approaches, ranging from
      electron and optical microscopy to magnetic resonance imaging, have been proposed
      to address the connectomics challenge on various spatial scales and in different
      species. Here, we review the main technological advances in the microscopy
      techniques applied to connectomics, highlighting the potential and limitations of
      the different methods. Finally, we briefly discuss the role of connectomics in
      the Human Brain Project, the Future and Emerging Technologies (FET) Flagship
      recently approved by the European Commission. 

PMID- 24139655
TI  - The Human Brain Project and neuromorphic computing.
AB  - Understanding how the brain manages billions of processing units connected via
      kilometers of fibers and trillions of synapses, while consuming a few tens of
      Watts could provide the key to a completely new category of hardware
      (neuromorphic computing systems). In order to achieve this, a paradigm shift for
      computing as a whole is needed, which will see it moving away from current "bit
      precise" computing models and towards new techniques that exploit the stochastic
      behavior of simple, reliable, very fast, lowpower computing devices embedded in
      intensely recursive architectures. In this paper we summarize how these
      objectives will be pursued in the Human Brain Project. 

PMID- 24139654
TI  - Brain investigation and brain conceptualization.
AB  - The brain of a patient with Alzheimer's disease (AD) undergoes changes starting
      many years before the development of the first clinical symptoms. The recent
      availability of large prospective datasets makes it possible to create
      sophisticated brain models of healthy subjects and patients with AD, showing
      pathophysiological changes occurring over time. However, these models are still
      inadequate; representations are mainly single-scale and they do not account for
      the complexity and interdependence of brain changes. Brain changes in AD patients
      occur at different levels and for different reasons: at the molecular level,
      changes are due to amyloid deposition; at cellular level, to loss of neuron
      synapses, and at tissue level, to connectivity disruption. All cause extensive
      atrophy of the whole brain organ. Initiatives aiming to model the whole human
      brain have been launched in Europe and the US with the goal of reducing the
      burden of brain diseases. In this work, we describe a new approach to earlier
      diagnosis based on a multimodal and multiscale brain concept, built upon existing
      and well-characterized single modalities. 

PMID- 24139656
TI  - Imaging connectivity: MRI and the structural networks of the brain.
AB  - Magnetic resonance imaging (MRI) is a flexible and widely available neuroimaging
      technique. Structural MRI and diffusion MRI, in particular, provide information
      about connectivity between brain regions which may be combined to obtain a
      picture of entire neural networks, or the so-called connectome. In this review we
      outline the principles of MR-based connectivity analysis, discuss what relevant
      information it can provide for clinical and non-clinical neuroscience research,
      and outline some of the outstanding needs which future work will aim to meet. 

PMID- 24139659
TI  - Functional neurology of a brain system: a 3D olfactory bulb model to process
      natural odorants.
AB  - The network of interactions between mitral and granule cells in the olfactory
      bulb is a critical step in the processing of odor information underlying the
      neural basis of smell perception. We are building the first computational model
      in 3 dimensions of this network in order to analyze the rules for connectivity
      and function within it. The initial results indicate that this network can be
      modeled to simulate experimental results on the activation of the olfactory bulb
      by natural odorants, providing a much more powerful approach for 3D simulation of
      brain neurons and microcircuits. 

PMID- 24139657
TI  - Awake surgery between art and science. Part I: clinical and operative settings.
AB  - Awake surgery requires coordinated teamwork and communication between the surgeon
      and the anesthesiologist, as he monitors the patient, the neuroradiologist as he
      interprets the images for intraoperative confirmation, and the neuropsychologist
      and neurophysiologist as they evaluate in real-time the patient's responses to
      commands and questions. To improve comparison across published studies on
      clinical assessment and operative settings in awake surgery, we reviewed the
      literature, focusing on methodological differences and aims. In complex,
      interdisciplinary medical care, such differences can affect the outcome and the
      cost-benefit ratio of the treatment. Standardization of intraoperative mapping
      and related controversies will be discussed in Part II. 

PMID- 24139658
TI  - Awake surgery between art and science. Part II: language and cognitive mapping.
AB  - Direct cortical and subcortical stimulation has been claimed to be the gold
      standard for exploring brain function. In this field, efforts are now being made
      to move from intraoperative naming-assisted surgical resection towards the use of
      other language and cognitive tasks. However, before relying on new protocols and
      new techniques, we need a multi-staged system of evidence (low and high) relating
      to each step of functional mapping and its clinical validity. In this article we
      examine the possibilities and limits of brain mapping with the aid of a visual
      object naming task and various other tasks used to date. The methodological
      aspects of intraoperative brain mapping, as well as the clinical and operative
      settings, were discussed in Part I of this review. 

PMID- 24139660
TI  - MRI observation of hippocampal degeneration in Alzheimer's disease: a forgotten
      case.
AB  - At the beginning of the 1990s, as part of work being done for a master's degree
      thesis in physics, an important observation of hippocampal degeneration in
      Alzheimer's disease was made in Pavia. However this result was never published in
      a full scientific paper. This case gives an idea of how an isolated observation
      can, in the right setting, develop into a real scientific achievement. 

PMID- 24139662
TI  - Assessing communities of practice in health policy: a conceptual framework as a
      first step towards empirical research.
AB  - Communities of Practice (CoPs) are groups of people that interact regularly to
      deepen their knowledge on a specific topic. Thanks to information and
      communication technologies, CoPs can involve experts distributed across countries
      and adopt a 'transnational' membership. This has allowed the strategy to be
      applied to domains of knowledge such as health policy with a global perspective.
      CoPs represent a potentially valuable tool for producing and sharing explicit
      knowledge, as well as tacit knowledge and implementation practices. They may also
      be effective in creating links among the different 'knowledge holders'
      contributing to health policy (e.g., researchers, policymakers, technical
      assistants, practitioners, etc.). CoPs in global health are growing in number and
      activities. As a result, there is an increasing need to document their progress
      and evaluate their effectiveness. This paper represents a first step towards such
      empirical research as it aims to provide a conceptual framework for the analysis
      and assessment of transnational CoPs in health policy.The framework is developed
      based on the findings of a literature review as well as on our experience, and
      reflects the specific features and challenges of transnational CoPs in health
      policy. It organizes the key elements of CoPs into a logical flow that links
      available resources and the capacity to mobilize them, with knowledge management
      activities and the expansion of knowledge, with changes in policy and practice
      and, ultimately, with an improvement in health outcomes. Additionally, the paper
      addresses the challenges in the operationalization and empirical application of
      the framework.

PMID- 24139663
TI  - Gender differences in match performance characteristics of soccer players
      competing in the UEFA Champions League.
AB  - The aim of this study was to examine gender differences in match performance
      characteristics of elite soccer players. Fifty-four male and fifty-nine female
      soccer players were tracked during UEFA Champions League matches using a multi
      camera system (Amisco, Nice, France). Male players covered more (P<.01) distance
      than female players in total during a match (Effect Size [ES]: 0.5) and at higher
      speed thresholds (>15, >18, 18-21, 21-23, 23-25 and >27kmh(-1); ES: 0.7-1.4).
      Decrements in the second versus first half (P<.01) were only evident in female
      players for the distance covered in total and at selected speed thresholds (12
      15, >12 and >15kmh(-1); ES: 0.6). Male central midfielders covered more (P<.01)
      total distance during a match than female central midfielders and at selected
      speed thresholds (15-23kmh(-1); ES: 1.3-2.2). Male full-backs and wide
      midfielders covered a greater distance (P<.01) than female players in the same
      positions at higher speed thresholds (>15, 21-23, 23-25, 25-27 and >27kmh(-1);
      ES: 1.5-3.1). The distance covered during the most intense 5min period of the
      match (>15kmh(-1)) was higher (P<.01) in male compared to female players (ES:
      1.0) but no distance deficit in the next versus the average 5min period was
      observed for either gender (ES: 0.1-0.2). No gender differences were found for
      technical events such as the number of ball touches, time in possession of the
      ball or total duels won during both halves and the entire match (ES: 0.1-0.3).
      However, female players lost the ball more often (P<.05) and displayed lower pass
      completion rates than male players during both halves and the entire match (ES:
      0.5-0.9). The data demonstrate that large gender differences exist for match
      performance characteristics of players competing at the highest competitive
      standard of European soccer. Such detailed analyses could be useful for gender
      specific training information for optimal preparation. However, more research is
      warranted to establish gender-specific speed thresholds for elite soccer players.

PMID- 24139661
TI  - Children with specific language impairment are not impaired in the acquisition
      and retention of Pavlovian delay and trace conditioning of the eyeblink response.
AB  - Three converging lines of evidence have suggested that cerebellar abnormality is
      implicated in developmental language and literacy problems. First, some brain
      imaging studies have linked abnormalities in cerebellar grey matter to dyslexia
      and specific language impairment (SLI). Second, theoretical accounts of both
      dyslexia and SLI have postulated impairments of procedural learning and
      automatisation of skills, functions that are known to be mediated by the
      cerebellum. Third, motor learning has been shown to be abnormal in some studies
      of both disorders. We assessed the integrity of face related regions of the
      cerebellum using Pavlovian eyeblink conditioning in 7-11year-old children with
      SLI. We found no relationship between oral language skills or literacy skills
      with either delay or trace conditioning in the children. We conclude that this
      elementary form of associative learning is intact in children with impaired
      language or literacy development. 

PMID- 24139664
TI  - Gender differences between muscle activation and onset timing of the four
      subdivisions of trapezius during humerothoracic elevation.
AB  - The aim of this study was to provide a description of gender differences of the
      normal muscle activation patterns of the four subdivisions of the trapezius
      (clavicular, descending, transverse, ascending) during arm elevation. Surface EMG
      was collected from these four subdivisions from twenty-two healthy subjects (12
      females, 10 males) during arm elevation in the scapular plane. Percent activation
      (RMS) of each subdivision was compared between genders across arm angles and
      elevation phase and onset time of each subdivision was compared between genders.
      Females demonstrated significantly higher % activation levels for each
      subdivision (p<.05), except transverse trapezius (p=.36). A statistically
      significant difference for onset time was observed between gender for the
      descending trapezius, with a slower onset time for females (p<.05). Findings from
      this study support the theory that subdivisions within descending trapezius are
      preferentially activated and demonstrate that gender differences are present
      within the fourth subdivision of trapezius. As subjects were without shoulder
      pathology, the observed gender differences may be explained by normal motor
      control variations. However, as coordinated activation of trapezius is required
      for normal shoulder motion, it is recommended to include all four subdivisions of
      trapezius and address gender differences in future studies. 

PMID- 24139665
TI  - Real-time, contextual intervention using mobile technology to reduce marijuana
      use among youth: a pilot study.
AB  - We evaluated the feasibility, acceptability, and potential efficacy of MOMENT, an
      intervention to reduce youth marijuana use that combines brief motivational
      enhancement therapy with mobile self-monitoring and responsive messaging. At
      baseline, primary care patients ages 15-24 who used marijuana frequently (at
      least 3 times per week) completed a recall assessment, then 1 week of mobile
      momentary and daily reports on use-related factors. For the intervention, youth
      participated in two motivational enhancement therapy sessions, during which they
      identified their top-3 social and emotional triggers for use and discussed
      healthy ways to manage them. They then completed two weeks of mobile reports.
      Upon reporting a top-3 trigger for use, desire to use, or recent use, they
      received a message supporting self-efficacy and prompting consideration of coping
      strategies. Generalized estimating equations examined changes in momentary-,
      daily-, and individual-level measures on 3-month recall and mobile assessments.
      Twenty-seven youth (M=19.2 years, 70% female) enrolled; there were 377-677
      momentary and 50-106 daily reports per study phase. Participants reported reading
      the messages and finding them motivating, being comfortable with participation,
      and not experiencing the study as burdensome. Although proportion of momentary
      reports of being in a top-3 trigger context did not change (36%-43%), marijuana
      desire in a top-3 trigger context and marijuana use after top-3 trigger exposure
      decreased over the study (p<.0001 and p=.03, respectively). Daily- and individual
      level measures showed similar, non-significant, improvements. The MOMENT
      intervention appears feasible, well-accepted, and potentially efficacious for
      youth who use marijuana frequently.

PMID- 24139666
TI  - A relic or still relevant: the narrowing role for vagotomy in the treatment of
      peptic ulcer disease.
AB  - BACKGROUND: Given the rise of medical treatment for peptic ulcer disease (PUD),
      surgical treatment is necessary only in select cases and emergencies. The authors
      assess the current relevance of surgical vagotomy to treat PUD and its
      complications. DATA SOURCES: Although historically significant, selective and
      highly selective vagotomy is very technically challenging, and highly selective
      vagotomy has a relatively narrow indication and high recurrence rates. Vagotomy
      and gastrectomy is associated with significant side effects. Two types of
      vagotomy remain relevant, within a narrow scope. Truncal vagotomy and
      pyloroplasty is safe and efficacious through a laparoscopic approach in certain
      emergent cases. Vagotomy and Roux-en-Y gastrojejunostomy can be used to treat
      severe PUD refractory to medical management. CONCLUSIONS: The role of vagotomy in
      the management of PUD has a rich history but predated pharmacologic control of
      acid and understanding of the role of Helicobacter pylori in the disease. Thus,
      the current role of vagotomy is significantly limited. Specifically, the emergent
      use of truncal vagotomy is warranted for patients who are either resistant or
      allergic to proton pump inhibitors.

PMID- 24139667
TI  - A surgical team with focus on staff education in a community hospital improves
      outcomes, costs and patient satisfaction.
AB  - BACKGROUND: Outcomes, decreased costs, and patient satisfaction are the driving
      forces of a successful surgical practice. METHODS: A surgical team was assembled
      on October 1, 2010, and educational sessions were implemented. The outcomes and
      costs for patients who underwent laparoscopic fundoplication and Heller myotomy
      before and after October 1, 2010, were compared. A Press Ganey patient
      satisfaction survey was mailed to all patients. RESULTS: There were 268
      procedures (103 before and 165 after October 1, 2010): 64 laparoscopic
      fundoplications and Heller myotomies (23 before and 41 after). There were
      significant reductions in median operating time (185 minutes [interquartile range
      {IQR}, 155 to 257 minutes] vs 126 minutes [IQR, 113 to 147 minutes]; P = .001),
      length of stay (2.0 days [IQR, 2.0 to 4.0 days] vs 1.0 day [IQR, 1.0 to 2.5
      days]; P = .05), operating room costs ($2,407 [IQR, $2,171 to $2,893] vs $2,147
      [IQR, $1,942 to $2,345]; P = .004), and hospital room costs ($937 [IQR, $799 to
      $2,159] vs $556 [IQR, $484 to $937]; P = .044). The survey showed significant
      improvements in patients' experiences in communication with nurses (P = .025),
      pain management (P = .000), communication about medications (P = .037), and
      discharge instructions (P = .024). CONCLUSIONS: Assembling a surgical team with
      focus on staff education has a significant impact on outcomes, costs, and patient
      satisfaction.

PMID- 24139668
TI  - Instructional design affects the efficacy of simulation-based training in central
      venous catheterization.
AB  - BACKGROUND: Simulation-based learning is a common educational tool in health care
      training and frequently involves instructional designs based on Experiential
      Learning Theory (ELT). However, little research explores the effectiveness and
      efficiency of different instructional design methodologies appropriate for
      simulations. The aim of this study was to compare 2 instructional design models,
      ELT and Guided Experiential Learning (GEL), to determine which is more effective
      for training the central venous catheterization procedure. METHODS: Using a quasi
      experimental randomized block design, nurse anesthetists completed training under
      1 of the 2 instructional design models. Performance was assessed using a
      checklist of central venous catheterization performance, pass rates, and critical
      action errors. RESULTS: Participants in the GEL condition performed significantly
      better than those in the ELT condition on the overall checklist score after
      controlling for individual practice time (F[1, 29] = 4.021, P = .027, Cohen's d =
      .71), had higher pass rates (P = .006, Cohen's d = 1.15), and had lower rates of
      failure due to critical action errors (P = .038, Cohen's d = .81). CONCLUSIONS:
      The GEL model of instructional design is significantly more effective than ELT
      for simulation-based learning of the central venous catheterization procedure,
      yielding large differences in effect size.

PMID- 24139669
TI  - A survey of American College of Surgery fellows evaluating their use of
      antibiotic prophylaxis in the placement of subcutaneously implanted central
      venous access ports.
AB  - BACKGROUND: Currently, there is no standard of care for prophylactic antibiotics
      (PABX) at the time of placement of fully implanted central venous access ports
      (CVAPs). A survey of fellows of the American College of Surgeons was undertaken
      to determine the current practice pattern of PABX in CVAP placement. METHODS: A
      survey was mailed to 5,000 fellows of the American College of Surgeons. RESULTS:
      The response rate was 21.7%, with 73.1% of respondents nonacademic surgeons. PABX
      were given by 88.2% of the respondents. Of those who did not use PABX, the
      primary reasons were "not justified" or "not standard of care." General comments
      regarding reasons for use of PABX included "medicolegal," "required by hospital,"
      and "liability." CONCLUSIONS: In this survey, the overwhelming majority of
      responding American College of Surgeons fellows indicated that they use
      preoperative antibiotic prophylaxis for CVAP placement, despite there being no
      accepted standard of care or definitive evidence regarding PABX use for fully
      implanted CVAPs.

PMID- 24139670
TI  - Comparison of laparoscopic versus open procedure in the treatment of recurrent
      inguinal hernia: a meta-analysis of the results.
AB  - BACKGROUND: The aim of this meta-analysis was to compare the effectiveness and
      complications of the laparoscopic procedure and open techniques in the treatment
      of recurrent inguinal hernias. METHODS: The electronic databases MEDLINE, Embase,
      PubMed, and Cochrane Library were used to search for randomized controlled trials
      and comparative trials about laparoscopic and open procedures on recurrent
      inguinal hernia repair from January 1999 to September 2012. RESULTS: A total of
      1,311 patients enrolled into 6 randomized controlled trials and 5 comparative
      studies were included in this meta-analysis. Our pooled data showed that the
      laparoscopic procedure was associated with a lower incidence of wound infection
      and a shorter sick leave. However, there were no differences in other
      complication rates or the operation time between the 2 methods. CONCLUSIONS: The
      laparoscopic technique in the treatment of recurrent inguinal hernia was
      associated with less wound infection rates and a faster recovery to normal
      activity, whereas other complication rates, including the re-recurrence rate,
      were comparable between these 2 methods. Laparoscopic and open procedures could
      be performed with equal operation time.

PMID- 24139671
TI  - The (f)utility of flexion-extension C-spine films in the setting of trauma.
AB  - BACKGROUND: Flexion-extension radiographs are often used to assess for removal of
      the cervical collar in the setting of trauma. The objective of this study was to
      evaluate their adequacy. We hypothesized that a significant proportion is
      inadequate. METHODS: This was a retrospective review of C-spine clearance at a
      level 1 trauma center. A trauma-trained radiologist interpreted all flexion
      extension radiographs for adequacy. Studies performed within 7 days of injury
      were considered acute. RESULTS: Three hundred fifty-five flexion-extension
      radiographs were examined. Ninety-five percent% of these studies were inadequate
      (51% because of the inability to visualize the top of T1, whereas 44% had less
      than 30 degrees  of angulation from neutral). Two hundred ten studies were
      performed acutely; of these, 97% were inadequate. When performed 7 days or longer
      from injury, 91% were inadequate. CONCLUSIONS: Injury to the C-spine may harbor
      significant consequences; therefore, its proper evaluation is critical. The
      majority of flexion-extension films are inadequate. As such, they should not be
      included in the algorithm for removal of the cervical collar. If used, adequacy
      must be verified and supplemental radiographic studies obtained as indicated.

PMID- 24139672
TI  - Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue
      dependency and requirement for S-adenosylmethionine-dependent methylation.
AB  - Impaired S-adenosylmethionine (SAM)-dependent transmethylation and methylation
      capacity feature in diseases related to obesity or aging, and selenium (Se)
      metabolism is altered in these states. We tested the hypothesis that SAM
      metabolism is required for methylation and excretion of Se in a rat model. Four
      hours after selenite and periodate-oxidized adenosine (POA; an inhibitor of SAM
      metabolism) were administered, circulating markers of single-carbon status were
      unchanged, except for decreased circulating phosphatidylcholine (P<.05). In
      contrast, liver and kidney SAM and S-adenosylhomocysteine were elevated (P<.05
      for all). Concentrations of total Se were significantly elevated in both liver
      (P<.001) and kidney (P<.01), however the degree of accumulation in liver was
      significantly greater than that of kidney (P<.05). Red blood cell Se levels were
      decreased (P=.01). Trimethylselenonium levels were decreased in liver and kidney
      (P=.001 for both tissues) and Se-methyl-N-acetylselenohexosamine selenosugar was
      decreased in liver (P=.001). Urinary output of both trimethylselenonium (P=.001)
      and selenosugar (P=.01) was decreased as well. Trimethylselenonium production is
      more inhibited by POA than is selenosugar production (P<.05). This work indicates
      that low molecular weight Se metabolism requires SAM-dependent methylation, and
      disrupting the conversion of SAM to S-adenosylhomocysteine prevents conversion of
      selenite and intermediate metabolites to final excretory forms, suggesting
      implications for selenium supplementation under conditions where transmethylation
      is suboptimal, such as in the case of obese or aging individuals. 

PMID- 24139673
TI  - Docosahexaenoic acid reduces cellular inflammatory response following permanent
      focal cerebral ischemia in rats.
AB  - Cellular inflammatory response plays an important role in ischemic brain injury
      and anti-inflammatory treatments in stroke are beneficial. Dietary
      supplementation with docosahexaenoic acid (DHA) shows anti-inflammatory and
      neuroprotective effects against ischemic stroke. However, its effectiveness and
      its precise modes of neuroprotective action remain incompletely understood. This
      study provides evidence of an alternative target for DHA and sheds light on the
      mechanism of its physiological benefits. We report a global inhibitory effect of
      3 consecutive days of DHA preadministration on circulating and intracerebral
      cellular inflammatory responses in a rat model of permanent cerebral ischemia.
      DHA exhibited a neuroprotective effect against ischemic deficits by reduction of
      behavioral disturbance, brain infarction, edema and blood-brain barrier
      disruption. The results of enzymatic assay, Western blot, real-time reverse
      transcriptase polymerase chain reaction and flow cytometric analysis revealed
      that DHA reduced central macrophages/microglia activation, leukocyte infiltration
      and pro-inflammatory cytokine expression and peripheral leukocyte activation
      after cerebral ischemia. In parallel with these immunosuppressive phenomena, DHA
      attenuated post-stroke oxidative stress, c-Jun N-terminal kinase (JNK)
      phosphorylation, c-Jun phosphorylation and activating protein-1 (AP-1) activation
      but further elevated ischemia-induced NF-E2-related factor-2 (Nrf2) and heme
      oxygenase-1 (HO-1) expression. DHA treatment also had an immunosuppressive effect
      in lipopolysaccharide/interferon-gamma-stimulated glial cultures by attenuating
      JNK phosphorylation, c-Jun phosphorylation and AP-1 activation and augmenting
      Nrf2 and HO-1 expression. In summary, we have shown that DHA exhibited
      neuroprotective and anti-inflammatory effects against ischemic brain injury and
      these effects were accompanied by decreased oxidative stress and JNK/AP-1
      signaling as well as enhanced Nrf2/HO-1 expression. 

PMID- 24139674
TI  - Item bank measurement of depression: will one dimension work?

PMID- 24139675
TI  - Diagnostic performance of rectal swab versus bulk stool specimens for the
      detection of rotavirus and norovirus: implications for outbreak investigations.
AB  - BACKGROUND: In January of 2008, during the peak of the rotavirus season in
      Guatemala, a gastroenteritis outbreak with high mortality among infants was
      reported in Guatemala. Despite extensive efforts, the investigation was limited
      by the lack of bulk stool specimens collected, particularly from the more
      severely dehydrated or deceased children. OBJECTIVES: We evaluated the diagnostic
      performance of rectal swab specimens compared with bulk stool for the detection
      of rotavirus and norovirus. STUDY DESIGN: Patients with diarrhea (>=3 loose
      stools in 24 h) were enrolled through an ongoing surveillance system in
      Guatemala. From January through March 2009, we attempted to enroll 100 patients
      <5 years old captured by the diarrhea surveillance, and collected paired bulk
      stool and rectal swabs specimens from them. Specimens were tested for norovirus
      using real-time reverse transcription-polymerase chain reaction and for rotavirus
      via enzyme immunoassay. RESULTS: We enrolled 102 patients with paired specimens;
      91% of 100 paired specimens tested for rotavirus yielded concordant results
      positive for rotavirus with a negativity rate of 83%. Among 100 paired specimens
      tested for norovirus, 86% were concordant norovirus detection and the negativity
      rate was 85%. The diagnostic performance for rotavirus and norovirus detection
      did not differ significantly between the two specimen types. CONCLUSIONS: Testing
      of properly collected fecal specimens using rectal swabs may be a viable
      alternative to bulk stool for detection of rotavirus and norovirus, particularly
      during outbreaks where collection of bulk stool may be difficult.

PMID- 24139676
TI  - Spigelian hernia treated by laparoscopy.

PMID- 24139677
TI  - Laparoscopic omega-loop gastric bypass for the conversion of failed sleeve
      gastrectomy: early experience.
AB  - OBJECTIVES: Despite the initial effectiveness of sleeve gastrectomy (SG), some
      patients who undergo this purely restrictive technique have inadequate weight
      loss or renewed weight gain and persistent obesity-related co-morbidities with
      their potentially lethal complications. In such patients, the conversion of SG by
      the addition of a malabsorptive technique may then be necessary. PATIENTS AND
      METHODS: Conversion of SG to a mini gastric bypass (MGBP) was evaluated for
      failure of weight loss. An ante-colic end-to-side stapled gastro-jejunal
      anastomosis was performed laparoscopically, connecting the long narrow gastric
      tube to the jejunum at a point 200cm downstream from the ligament of Treitz.
      RESULTS: Between October 2006 and February 2012, 651 laparoscopic MGBP were
      performed for morbid obesity. Twenty-three of these patients (3.5%) had
      previously undergone SG. The conversion from SG to MGPB was performed
      laparoscopically in 19 of the 23 patients (81%) at a mean interval of 26.3months
      (8.2-63.7). The 30-day postoperative mortality rate was zero and the morbidity
      rate was 9.5%. The mean BMI before MGBP was 44+/-7.7kg (35.8-55.4). Conversion of
      SG to MGBP resulted in additional weight loss, achieving a mean BMI of 39.9 with
      a 26.8% loss of excess BMI (EBL) at 3months, mean BMI of 36.5 with 37.2% EBL at
      12months, mean BMI of 36.2 with 48.6% EBL at 18months, and mean BMI of 35.7 with
      EBL of 51.6% at 24months. The overall mean EBL was 57.3+/-19.5% (range: 25-82%)
      at 42.3months (range 16.7-60.8months). CONCLUSION: Conversion of SG to MGBP is
      feasible, safe and effective, and results in significant additional weight loss.
      Definitive results at 2 and 5years are awaited for the long-term procedure
      validation.

PMID- 24139678
TI  - Space, place and the midwife: exploring the relationship between the birth
      environment, neurobiology and midwifery practice.
AB  - BACKGROUND: Research indicates that midwives and their practice are influenced by
      space and place and that midwives practice differently in different places. It is
      possible that one mechanism through which space and place influence midwifery
      practice is via neurobiological responses such as the production and release of
      oxytocin, which can be triggered by experiences and perceptions of the physical
      environment. AIM: To articulate the significance of space and place to midwifery
      and explore the relationship between the birth environment, neurobiology and
      midwifery practice. DISCUSSION: Quality midwifery care requires the facilitation
      of trusting social relationships and the provision of emotionally sensitive care
      to childbearing women. The neuropeptide oxytocin plays a critical role in human
      social and emotional behaviour by increasing trust, reducing stress and
      heightening empathy, reciprocity and generosity. PRINCIPLE CONCLUSION: Through
      its role as a trigger for oxytocin release, the birth environment may play a
      direct role in the provision of quality midwifery care.

PMID- 24139679
TI  - Making an IMPACT in traumatic brain injury research.

PMID- 24139681
TI  - "The problem with running"--comparing the propulsion strategy of children with
      developmental coordination disorder and typically developing children.
AB  - Children with Developmental Coordination Disorder (DCD) often have difficulties
      running. This study compared strategies of propulsion and power generation at the
      ankle during late stance/early swing in both walking and running in children with
      and without DCD. Eleven children (six male) aged nine to 12 years with DCD were
      matched by sex and age with 11 typically developing (TD) children. Gait
      kinematics and kinetics were measured during 4 gait types; normal walking, fast
      walking, jogging and sprinting using three-dimensional motion analysis.
      Propulsion strategy during gait was calculated as ankle power divided by the sum
      of ankle and hip power (A2/A2+H3). The children with DCD ran slower than the TD
      children (mean difference [MD] when jogging 0.3m/s and sprinting 0.8m/s).
      Adjusting for speed, those with DCD had smaller propulsion strategy values during
      jogging (p=0.001) and sprinting (p=0.012), explained by reduced ankle power
      generation at push off (A2) (jogging, MD 2.5 W/kg, p<0.001) and greater hip
      flexor power generation at pull off (H3) (jogging, MD 0.75 W/kg, p=0.013).
      Similar findings were observed during sprinting. Children with DCD ran with a
      slow and less efficient running style compared with TD children. Physiotherapy
      targeting running-specific needs in relation to ankle muscle strength and
      coordination could enable more participation in running activities.

PMID- 24139680
TI  - Advancing care for traumatic brain injury: findings from the IMPACT studies and
      perspectives on future research.
AB  - Research in traumatic brain injury (TBI) is challenging for several reasons; in
      particular, the heterogeneity between patients regarding causes, pathophysiology,
      treatment, and outcome. Advances in basic science have failed to translate into
      successful clinical treatments, and the evidence underpinning guideline
      recommendations is weak. Because clinical research has been hampered by non
      standardised data collection, restricted multidisciplinary collaboration, and the
      lack of sensitivity of classification and efficacy analyses, multidisciplinary
      collaborations are now being fostered. Approaches to deal with heterogeneity have
      been developed by the IMPACT study group. These approaches can increase
      statistical power in clinical trials by up to 50% and are also relevant to other
      heterogeneous neurological diseases, such as stroke and subarachnoid haemorrhage.
      Rather than trying to limit heterogeneity, we might also be able to exploit it by
      analysing differences in treatment and outcome between countries and centres in
      comparative effectiveness research. This approach has great potential to advance
      care in patients with TBI. 

PMID- 24139682
TI  - Test-retest reliability of three dimensional gait analysis: including a novel
      approach to visualising agreement of gait cycle waveforms with Bland and Altman
      plots.
AB  - BACKGROUND/AIM: Estimating the measurement error (reliability) of three
      dimensional gait analysis (3DGA) is crucial to interpretation of gait data. The
      purpose of this study was to investigate the intra-rater reliability of 3DGA and
      apply a novel method of visualising reliability of gait cycle waveforms. METHODS:
      A test re-test design was employed. A convenience sample of 30 healthy adults
      (18F; 12 M: mean age 30 +/- 6.8 years) participated. Subjects walked along a 10 m
      walkway at their preferred gait speed and 3DGA data were collected using a
      VICON((r)) 3DGA system. Testing was performed by the same investigator on two
      separate days within two weeks. Data from 10 trials were averaged and analysed.
      ANALYSIS: The intraclass correlation coefficient (ICC), the standard error of
      measurement (SEM), minimal detectable change (MDC) and limits of agreement were
      calculated for kinetic and kinematic data. Bland and Altman plots were applied to
      gait cycle waveforms. RESULTS: Spatio-temporal parameters such as cadence, step
      length, velocity, step time and step width were highly repeatable generating
      ICC's of 0.90 and above and low SEM/MDC. Range of joint movement across the gait
      cycle was generally more reliable than either minimum or maximum values and
      higher ICCs were obtained for movement in the sagittal plane. For kinematic data
      the standard error of measurement was low (<= 5) for the majority of parameters.
      Transverse plane measurements showed poor reliability with lowest ICC's. ICCs for
      kinetic data ranged from 0.51 to 0.81. CONCLUSIONS: Reliability of 3DGA has been
      estimated for our gait laboratory. Bland and Altman plots of gait cycle waveforms
      provide a useful addition to reliability analysis.

PMID- 24139683
TI  - What would you do? The effect of verbal persuasion on task choice.
AB  - Verbal persuasion has been shown to influence psychological and behavioral
      outcomes. The present study had two objectives: (1) to examine the effect of
      verbal persuasion on task choice in a balance setting and (2) to evaluate the use
      of verbal persuasion as an approach to experimentally induce mismatches between
      perceived and actual balance. Healthy young adults (N=68) completed an 8-m tandem
      walk task without vision and then were randomly assigned to a feedback group
      (good, control, or poor), regardless of actual balance. Following the feedback,
      participants chose to perform the task in one of three conditions differing in
      level of challenge and also were required to perform the task under the same pre
      feedback conditions. Balance efficacy and perceived stability were rated before
      and after each pre- and post-feedback task, respectively. Balance performance
      measures were also collected. Following the feedback, participants in the good
      group were more likely to choose the most challenging task while those in the
      poor group were more likely to choose the least challenging task. Following the
      feedback, all groups showed improved balance performance. However, balance
      efficacy and perceived stability increased for the good and control groups but
      balance efficacy decreased and perceived stability was unchanged for the poor
      group. Thus, these findings demonstrate that verbal persuasion can influence task
      choice and may be used as an approach to experimentally create mismatches between
      perceived and actual balance. 

PMID- 24139684
TI  - A new look at an old problem: defining weight acceptance in human walking.
AB  - BACKGROUND: Weight acceptance (WA) is an important phase of bipedal gait that has
      received relatively little study to date. This study tested the hypothesis that
      the first peak knee flexion would better demarcate the end of WA power absorption
      activity across varying gait speeds than would the more commonly used event of
      contralateral toe off (CTO) or the peak hip adduction angle. METHODS: Eight
      control subjects (4F/4M) walked on a treadmill at slow, self-selected, and fast
      speeds. Kinematic and kinetic data were recorded. Joint angles and power
      absorption were analyzed about the, lower extremity joints (sagittal ankle, knee,
      hip and frontal hip). Differences in event timings and, magnitudes of negative
      work were analyzed (ANOVA). RESULTS: Knee sagittal power absorption continued
      after the CTO event at self-selected (p=0.009) and fast speeds (p=0.001), while
      hip frontal power absorption continued after the CTO event at slow (p=0.019),
      self-selected (p=0.001), and fast speeds (p=0.001). The contribution of frontal
      hip to overall power absorption increased as speed decreased. DISCUSSION: Peak
      hip adduction angle is the best kinematic marker of the end of the WA phase, and
      peak knee flexion angle is the best alternative marker across speeds. CTO is only
      appropriate to use when gait speeds are slow. In addition, the relative
      contribution of power absorbed in the frontal hip during WA highlights the
      importance of frontal plane pelvic control in locomotion, especially when gait
      speed is slow.

PMID- 24139685
TI  - Evaluation of age-related differences in the stride-to-stride fluctuations,
      regularity and symmetry of gait using a waist-mounted tri-axial accelerometer.
AB  - PURPOSE: To compare the stride-to-stride fluctuations, regularity and symmetry of
      gait using a body-fixed accelerometer in a group of healthy young and healthy
      older adults. METHODS: Forty-one healthy young adults (24 +/- 3 years) and forty
      one healthy older adults (76 +/- 5 years) completed a 10-min walk at a self
      selected, normal walking speed while wearing a single waist-mounted tri-axial
      accelerometer. The following gait parameters were compared between age groups:
      mean step and stride time, step and stride time variability, stride time fractal
      scaling index and the regularity and symmetry of the acceleration pattern in the
      vertical, mediolateral and anteroposterior directions (unbiased autocorrelation
      procedure). RESULTS: Older adults displayed significantly greater step and stride
      time variability (p<0.05) and a lower stride time fractal scaling index (p<0.01),
      as well as significantly less regularity (p<0.05) and symmetry (p<0.05) of the
      anteroposterior accelerations. CONCLUSION: The results show that healthy older
      adults possess greater temporal gait variability, as well as a less-organized and
      repeatable pattern of variability and acceleration in the direction of motion,
      than younger adults. The findings also suggest the presence of an age-related
      decline in the anteroposterior control of gait, but not in the vertical and
      mediolateral control of gait.

PMID- 24139686
TI  - Utilisation of skilled birth attendance in Northern Nigeria: a cross-sectional
      survey.
AB  - OBJECTIVE: to determine the level and determinants for utilisation of Skilled
      Birth Attendance (SBA). METHODS: a population-based survey using a structured
      questionnaire was conducted in Goya and Tundunya political wards of Katsina state
      from May to June 2012. Four hundred women aged 15-49 years who had delivered a
      baby within two years prior to the study were asked about birth attendance during
      antenatal care (ANC), childbirth and postnatal period of their most recent birth.
      Logistic regression analysis was performed to obtain independent predictors of
      skilled birth attendance (SBA). FINDINGS: of the 400 women recruited for the
      study, 145 (36.3%) received antenatal care, 52 (13%) had their births assisted by
      skilled personnel and 88 (22%) received postnatal care from skilled birth
      attendants. Of the 52 women who had their births attended by skilled birth
      attendants only 29 (56%) had their births in a health facility. Maternal
      education, husband's occupation, presence of complication and previous place of
      childbirth were found to be statistically significant predictors for SBA
      utilisation. Barriers to SBA utilisation identified included lack of health care
      provider, lack of equipment and supplies and poverty. Enablers mentioned included
      availability of staff, husband's approval and affordable service. CONCLUSION:
      women are more likely to utilise SBA with the availability of skilled personnel,
      strengthening of the health system and intervention to remove user fees for
      maternal health services. Joint effort should be made by government and community
      leaders to promote girl's education and to encourage men's involvement in
      maternal health services.

PMID- 24139687
TI  - Critical realism: an important theoretical perspective for midwifery research.
AB  - BACKGROUND: there is a dearth of papers in midwifery journals exploring the
      philosophical underpinnings of various research methods. However, explaining and
      justifying particular ontological and epistemological positions gives coherence
      and credibility to chosen research methods. OBJECTIVES: to explore and explain
      the philosophical underpinning of critical realism and argue for it to be more
      widely adopted by midwifery researchers, using the exemplar of dystocia research.
      DISCUSSION: critical realism as originally espoused by Bhaskar sees reality as
      layered (realist ontology) and seeks to explore causative mechanisms for what is
      experienced and observed. In this way it illuminates the complexity of health
      care, though recognising that knowledge of this complexity is filtered through an
      interpretive lens (constructionist epistemology). Critical realism encourages a
      holistic exploration of phenomena, premised on multiple research questions that
      utilise multiple research methods. IMPLICATIONS FOR RESEARCH: critical realism as
      a philosophical underpinning is therefore particularly apposite for researching
      midwifery issues and concerns.

PMID- 24139688
TI  - Evaluation of sub-cellular distribution of glutamate dehydrogenase (GDH) in
      Drosophila melanogaster larvae.
AB  - Glutamate dehydrogenase (GDH) enzyme was conventionally known as a mitochondrial
      marker. However, subsequently it was reported to be present in the nuclei as
      well. So far, the nuclear distribution of GDH has been reported in a number of
      organisms including yeast, rat, cow, chicken. However, the sub-cellular
      distribution of GDH, illustrated by in situ methods still remains elusive. Here,
      by assaying the GDH activity and by immuno-blotting using anti-GDH antibody in
      the fractionated nuclear and cytoplasmic fractions of Drosophila larvae, we
      demonstrate the cytoplasmic distribution of GDH. This observation was further
      supported by in situ immunostaining of salivary gland, Malpighian tubules and eye
      imaginal discs of Drosophila larvae. Collectively, our results demonstrate that
      in Drosophila larvae, GDH is not found in the nucleus, but is localized
      exclusively in the cytoplasm. 

PMID- 24139689
TI  - The influence of Sildenafil citrate on uterine tissue perfusion and the
      cardiovascular system during the luteal phase of the ovarian cycle in cows.
AB  - The aim of the study was to evaluate the influence of the Sildenafil citrate on
      the blood flow in the uterus of cows during dioestrus. Uterine blood flow was
      examined in five, healthy, adult cows. Between day 6-8 of the ovarian cycle, each
      cow received 200mg of sildenafil diluted in 10ml of warm saline into the body of
      the uterus. Analysis of the blood pressure, ECG and the maximum velocity in m/s
      (V max) in the aorta was performed and selected parameters of the blood flow (PI,
      pulsatile index; RI, resistance index; SPV, systolic peak velocity; EDV, end
      diastolic velocity; FVI, flow velocity integral; SV/DV, systolic peak velocity:
      end-diastolic velocity ratio) were measured in the uterine artery (Arteria
      uterine) before and after sildenafil infusion. In addition, Color Doppler
      examination of the uterine wall perfusion was analyzed. A significant decrease of
      values of PI and SV/DV ratio as well as an increase of end diastolic velocity and
      time averaged maximum velocity was noted. With the use of color coded sonography,
      the increased intensity of the blood flow in the uterine wall was observed. It
      was concluded that intrauterine administration of sildenafil during dioestrus can
      increase uterine tissue perfusion. 

PMID- 24139690
TI  - Issues of reporting in observational studies in veterinary medicine.
AB  - Observational studies are common in veterinary medicine; the results may be used
      to inform decision-making, future research, or as inputs to systematic reviews or
      risk assessment. To be of use, the results must be published, all of the outcomes
      that were assessed must be included in the publication, and the research (methods
      and results) must be reported in sufficient detail that the reader can evaluate
      the internal and external validity. In human healthcare, concerns about the
      completeness of reporting - and evidence that poor reporting is associated with
      study results - have led to the creation of reporting guidelines; these include
      the STROBE statement for observational studies. There is evidence from a limited
      body of research that there also are reporting inadequacies in veterinary
      observational studies. There are differences between human and veterinary
      observational studies that might be relevant to recommendations for reporting.
      Such differences include: the use of observational studies in animal populations
      for simultaneously estimating disease frequency and risk-factor identification;
      the distinction between the animal owners who consent to participate and the
      animals that are the study subjects; and the complexity of organizational levels
      inherent in animal research (in particular, for studies in livestock species). In
      veterinary medicine, it is common to have clustering within outcomes (due to
      animal grouping) and clustering of predictor variables. We argue that there is a
      compelling need for the scientific community involved in veterinary observational
      studies to use the STROBE statement, use an amended version of STROBE, or to
      develop and use reporting guidelines that are specific to veterinary medicine to
      improve reporting of these studies. 

PMID- 24139691
TI  - Oncology scan--improving our understanding of the local management of breast
      cancer.

PMID- 24139692
TI  - Neuroregulation of cutaneous microcirculation: the shadow of Sir Thomas Lewis.

PMID- 24139693
TI  - Biotechnology for a healthy and green world.

PMID- 24139695
TI  - Transplanted germ cells persist long-term in irradiated ram testes.
AB  - Testicular germ cell transplantation provides a tool to study transgenesis,
      spermatogenesis and to increase production efficiency in livestock industries.
      Isolated testicular germ cells can be transplanted into testes of livestock
      breeds to generate sperm of donor origin. In sheep, methods have been developed
      previously to isolate cell populations from ram testes and transplant these into
      irradiated testes of recipient rams. This has resulted in rams producing sperm
      derived from the donor cells and a number of the recipient animals have produced
      donor-derived offspring from the introduced spermatogonial cells. Microsatellite
      genotyping data presented here demonstrates that these rams continue to produce
      sperm of donor origin for at least 5 years post-transplantation. This research
      provides new evidence of the stability of transplanted germ cells in a
      commercially important species, and with further refinements to cell isolation,
      transplantation and recipient preparation, this technology should find use in
      breeding systems to increase livestock production efficiency. 

PMID- 24139696
TI  - Mutations in genes involved in oestrous cycle associated expression of oestrus.
AB  - Detection of oestrus is a key determinant of profitability of dairy herds, but
      oestrus is increasingly difficult to observe in the modern dairy cow, with
      shorter duration and less intense oestrus. Concurrent with the unfavourable
      correlation between milk yield and fertility, oestrous detection rates have
      decreased to less than 50%. A number of mutations have been identified in genes
      associated with fertility and production traits, but, to date, no single
      nucleotide polymorphism (SNP) has been associated with oestrous expression.
      Therefore, the objective of this study was to investigate SNPs, linked to
      fertility, for the association with oestrous expression. Blood was collected from
      205 Holstein Friesian dairy cows and genotyped at 41 loci of 18 genes chosen for
      their roles in the oestrous cycle and milk production. SNPs were then examined
      for correlations with increase in activity at oestrus, recorded via activity
      monitors, using generalised linear models. Physical activity increased at oestrus
      between two and four fold. Larger increases were associated with mutant alleles
      in oestrogen receptor-alpha and gonadotrophin releasing hormone receptor genes
      (P<0.05) and in the STAT5A gene (P<0.05). Smaller increases were associated with
      mutant alleles of the activin receptor type IIB and prolactin receptor genes
      (P<0.10). In conclusion, alleles in these five genes provide the opportunity for
      selection of animals displaying greater oestrous activity which could aid
      reversal of the decrease in oestrous detection and thereby contribute to
      sustainability of the dairy industry worldwide. 

PMID- 24139694
TI  - Developmental imaging genetics: linking dopamine function to adolescent behavior.
AB  - Adolescence is a period of development characterized by numerous neurobiological
      changes that significantly influence behavior and brain function. Adolescence is
      of particular interest due to the alarming statistics indicating that mortality
      rates increase two to three-fold during this time compared to childhood, due
      largely to a peak in risk-taking behaviors resulting from increased impulsivity
      and sensation seeking. Furthermore, there exists large unexplained variability in
      these behaviors that are in part mediated by biological factors. Recent advances
      in molecular genetics and functional neuroimaging have provided a unique and
      exciting opportunity to non-invasively study the influence of genetic factors on
      brain function in humans. While genes do not code for specific behaviors, they do
      determine the structure and function of proteins that are essential to the
      neuronal processes that underlie behavior. Therefore, studying the interaction of
      genotype with measures of brain function over development could shed light on
      critical time points when biologically mediated individual differences in complex
      behaviors emerge. Here we review animal and human literature examining the
      neurobiological basis of adolescent development related to dopamine
      neurotransmission. Dopamine is of critical importance because of (1) its role in
      cognitive and affective behaviors, (2) its role in the pathogenesis of major
      psychopathology, and (3) the protracted development of dopamine signaling
      pathways over adolescence. We will then focus on current research examining the
      role of dopamine-related genes on brain function. We propose the use of imaging
      genetics to examine the influence of genetically mediated dopamine variability on
      brain function during adolescence, keeping in mind the limitations of this
      approach. 

PMID- 24139697
TI  - Circulating miR-125b as a biomarker of Alzheimer's disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous small RNAs of 21-25 nucleotides
      that post-transcriptionally regulate gene expressions. Recently, circulating
      miRNAs have been reported as promising biomarkers for neurodegenerative disorders
      and processes affecting the central nervous system. This study was conducted to
      investigate the potential role of serum miRNAs as diagnostic biomarkers for
      Alzheimer's disease (AD). METHODS: Serum samples were obtained from 105 probable
      AD patients and 150 age- and gender-matched normal controls. The serum
      concentrations of miRNAs miR-9, miR-29a, miR-29b, miR-101, miR-125b, and miR-181c
      were measured with a real-time quantitative reverse transcriptase PCR (qRT-PCR)
      method. RESULTS: We found both miR-125b and miR-181c were down-regulated while
      miR-9 was up-regulated in serum of AD patients compared with that of normal
      controls. Among the receiver operating characteristic (ROC) results, miR-125b
      alone showed its priority with a specificity up to 68.3% and a sensitivity of
      80.8%. Importantly, miR-125b was correlated with the Mini Mental State
      Examination (MMSE) in AD patients. CONCLUSIONS: Our results indicate that serum
      miR-125b may serve as a useful noninvasive biomarker for AD.

PMID- 24139698
TI  - Neuroradiologic correlates of clinical disability and progression in the X-linked
      leukodystrophy Pelizaeus-Merzbacher disease.
AB  - OBJECTIVE: To determine whether quantitative measure of magnetic resonance
      imaging data from patients with the inherited leukodystrophy, Pelizaeus
      Merzbacher disease (PMD) correlates with clinical severity or progression.
      METHODS: In our current work we have analyzed the clinical phenotypes and MRI
      scans of 51 male patients with PMD and 10 female carriers for whom the PLP1
      genotype had been determined. In addition, we developed a 32-point functional
      disability scoring (FDS) system for PMD, and validated it for inter-rater
      reliability. Using conventional T1- and T2-weighted MRI images of the whole
      brain, we measured white matter and total brain volume (WMV and TBV), inter
      caudate ratio (ICR), and corpus callosum area. RESULTS: There was a significant
      positive correlation of FDS with white matter fraction (WMV/TBV) and corpus
      callosum area. Also, when applying a median split based on FDS, patients with
      lower FDS showed reduced white matter fraction and corpus callosum area, and
      increased ICR compared to patients with relatively higher FDS, regardless of age.
      CONCLUSION: Although this patient population is heterogeneous, with multiple
      genetic and molecular mechanisms causing PMD, these data imply that white matter
      atrophy is a major pathological determinant of the clinical disability in most
      patients. Development of reliable non-invasive quantitative biomarkers of disease
      activity would be useful not only for following the natural history of the
      disease, but also raising the potential for evaluating future therapies.

PMID- 24139699
TI  - "A" motor neuron disease.
AB  - IMPORTANCE: Allgrove syndrome is a rare autosomal recessive disorder
      characterised by achalasia, alacrima, adrenal insufficiency, autonomic
      dysfunction and amyotrophy. The syndrome has been described in childhood and
      adult presentation, as in our case, is very rare. There is a considerable delay
      in diagnosis due to lack of awareness about the syndrome. OBSERVATIONS: We report
      a single case of a 36 year old man who was initially diagnosed and treated for
      achalasia cardia in our institute 14 years before. After 8 years he presented
      again with weakness and wasting predominantly distally. He had tongue
      fasciculations, brisk reflexes and extensor plantar. After supportive
      electrophysiological studies he was diagnosed as Amyotrophic lateral sclerosis.
      After 5 years he presented with generalised fatigue without any significant
      worsening of his neurological status. On reevaluation he had alacrimia, autonomic
      dysfunction and mild ACTH resistance. CONCLUSIONS AND RELEVANCE: Allgrove
      syndrome may be an underdiagnosed cause of multisystem neurological disease due
      to the heterogeneous clinical presentation as well as for ignorance of clinician
      about the syndrome. Based on our case, we also believe that there does exist a
      subgroup of patients who follow a less severe and chronic course. Recognition of
      syndrome allows for treatment of autonomic dysfunction, adrenal insufficiency and
      dysphagia.

PMID- 24139700
TI  - SIRT2 polymorphism rs10410544 is associated with Alzheimer's disease in a Han
      Chinese population.
AB  - Sirtuin 2 (SIRT2) is a strong protein deacetylase, which is highly expressed in
      central nervous system. Recently, an association between SIRT2 rs10410544
      polymorphism and late-onset Alzheimer's disease (LOAD) was found in the
      APOEepsilon4-negative Caucasian population. To investigate the potential
      association between the rs10410544 C/T polymorphism of SIRT2 and the risk of
      LOAD, we conducted an independent replication case-control study in a Northern
      Han Chinese population comprising 1133 cases and 1159 healthy controls being
      matched for age and gender. The results revealed that there were significant
      differences in genotype and allele frequencies between LOAD cases and controls
      (genotype P=0.008, allele P=0.009). When compared with the C allele, the T allele
      of rs10410544 demonstrated a 1.709-fold risk for developing LOAD. After
      stratification by apolipoprotein E (APOE) epsilon4-carrying status, only
      APOEepsilon4 noncarriers (P=0.035, adjusted OR=1.656, 95% CI: 1.036-2.647) showed
      the relation between LOAD and SIRT2 rs10410544 T allele. This study provides the
      evidence that the rs10410544 C/T polymorphism of SIRT2 was associated with
      genetic susceptibility to LOAD in a Northern Han Chinese population. 

PMID- 24139701
TI  - Distribution of hepatitis B virus subgenotype F2a in Sao Paulo, Brazil.
AB  - BACKGROUND: HBV genotype F is primarily found in indigenous populations from
      South America and is classified in four subgenotypes (F1 to F4). Subgenotype F2a
      is the most common in Brazil among genotype F cases. The aim of this study was to
      characterize HBV genotype F2a circulating in 16 patients from Sao Paulo, Brazil.
      Samples were collected between 2006 and 2012 and sent to Hospital Israelita
      Albert Einstein. A fragment of 1306 bp partially comprising HBsAg and DNA
      polymerase coding regions was amplified and sequenced. Viral sequences were
      genotyped by phylogenetic analysis using reference sequences from GenBank
      (n=198), including 80 classified as subgenotype F2a. Bayesian Markov chain Monte
      Carlo simulation implemented in BEAST v.1.5.4 was applied to obtain the best
      possible estimates using the model of nucleotide substitutions GTR+G+I. FINDINGS:
      It were identified three groups of sequences of subgenotype F2a: 1) 10 sequences
      from Sao Paulo state; 2) 3 sequences from Rio de Janeiro and one from Sao Paulo
      states; 3) 8 sequences from the West Amazon Basin. CONCLUSIONS: These results
      showing for the first time the distribution of F2a subgenotype in Brazil. The
      spreading and the dynamic of subgenotype F2a in Brazil requires the study of a
      higher number of samples from different regions as it is unfold in almost all
      Brazilian populations studied so far. We cannot infer with certainty the origin
      of these different groups due to the lack of available sequences. Nevertheless,
      our data suggest that the common origin of these groups probably occurred a long
      time ago.

PMID- 24139702
TI  - Hepatitis C screening and evaluation: clinical decision tool.

PMID- 24139703
TI  - Hepatitis C screening: summary of recommendations from the clinical decision
      tool.

PMID- 24139704
TI  - A comparison of the pharmacodynamic profiles of insulin detemir and insulin
      glargine: a single dose clamp study in people with type 2 diabetes.
AB  - AIM: The pharmacodynamic properties of a single dose of 0.5 U/kg insulin detemir
      and insulin glargine were compared during two 24-h isoglycaemic clamps, one week
      apart. METHODS: The order of treatments was randomised. At approximately 0830 h,
      persons with T2DM received subcutaneous administration of a 0.5 U/kg dose of
      either insulin detemir or insulin glargine into the anterior abdominal wall.
      Plasma glucose was measured at 10-min intervals throughout the 24-h clamp period
      and isoglycaemia was maintained by variable infusion of 20% glucose. Glucose
      infusion rates (GIR) and plasma C-peptide were determined throughout each 24-h
      period. RESULTS: Eleven persons with type 2 diabetes (8 male) with mean (SD) age
      58.5 years (8.5), BMI 30.8 kg/m2 (2.8) and HbA1c 7.5% (0.6) were studied. Plasma
      glucose remained constant during the clamp (CV: insulin detemir 3.7%; insulin
      glargine 3.8%). Following injection of insulin detemir, GIR increased, reaching a
      mean peak of 2.29 mg/kg/min (95% CI 1.64, 2.94) at 11.6h (range 8.9 to 14.3)
      compared to 1.71 mg/kg/min (95% CI 1.4, 2.0) at 10.2 h (8.1 to 12.3) for insulin
      glargine (P=0.025 for GIR(max)). Plasma C-peptide decreased during the study
      period, remaining significantly lower than the fasting level at the study end
      after both analogues, insulin detemir (P=0.01) and insulin glargine (P=0.02).
      CONCLUSION: In persons with T2DM, no difference in duration of action following a
      single subcutaneous dose of insulin detemir and insulin glargine could be
      observed. Insulin detemir showed greater between subject variability and achieved
      a significantly higher maximum GIR than insulin glargine.

PMID- 24139705
TI  - Telemedicine and type 1 diabetes: is technology per se sufficient to improve
      glycaemic control?
AB  - AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a
      website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly
      controlled type 1 diabetes. The system provided two main functions: automated
      advice on the insulin doses required; and remote monitoring by teleconsultation.
      The question is: how much did each function contribute to the improvement in
      HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor
      (IDA) and with (G3 group) or without (G2 group) the
      telemonitoring/teleconsultation function. Patients were classified as "high
      users" if the proportion of "informed" meals using the IDA exceeded 67% (median)
      and as "low users" if not. Also analyzed was the respective impact of the IDA
      function and teleconsultations on the final HbA1c levels. RESULTS: Among the high
      users, the proportion of informed meals remained stable from baseline to the end
      of the study 6months later (from 78.1+/-21.5% to 73.8+/-25.1%; P=0.107), but
      decreased in the low users (from 36.6+/-29.4% to 26.7+/-28.4%; P=0.005). As
      expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2%
      [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of
      telemonitoring/teleconsultation (-0.49+/-0.60% vs -0.52+/-0.73%, respectively;
      P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1]
      to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show
      greater improvement than the others (-0.93+/-0.97 vs -0.46+/-1.05, respectively;
      P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high
      and low users who avidly used the IDA function, while the greatest improvement
      was seen in the low users who had the motivational support of teleconsultations.

PMID- 24139706
TI  - Dialectal differences in hemispheric specialization for Japanese lexical pitch
      accent.
AB  - Language experience can alter perceptual abilities and the neural specialization
      for phonological contrasts. Here we investigated whether dialectal differences in
      the lexical use of pitch information lead to differences in functional
      lateralization for pitch processing. We measured cortical hemodynamic responses
      to pitch pattern changes in native speakers of Standard (Tokyo) Japanese, which
      has a lexical pitch accent system, and native speakers of 'accentless' dialects,
      which do not have any lexical tonal phenomena. While the Standard Japanese
      speakers showed left-dominant responses in temporal regions to pitch pattern
      changes within words, the accentless dialects speakers did not show such left
      dominance. Pitch pattern changes within harmonic-complex tones also elicited
      different brain activation patterns between the two groups. These results
      indicate that the neural processing of pitch information differs depending on the
      listener's native dialect, and that listeners' linguistic experiences may further
      affect the processing of pitch changes even for non-linguistic sounds. 

PMID- 24139707
TI  - Lessons from the Liverpool Care Pathway--evidence is key.

PMID- 24139708
TI  - Liverpool Care Pathway for patients with cancer in hospital: a cluster randomised
      trial.
AB  - BACKGROUND: The quality of care provided to patients with cancer who are dying in
      hospital and their families is suboptimum. The UK Liverpool Care Pathway (LCP)
      for patients who are dying was developed with the aim of transferring the best
      practice of hospices to hospitals. We therefore assessed the effectiveness of LCP
      in the Italian context (LCP-I) in improving the quality of end-of-life care for
      patients with cancer in hospitals and for their family. METHODS: In this
      pragmatic cluster randomised trial, 16 Italian general medicine hospital wards
      were randomly assigned to implement the LCP-I programme or standard health-care
      practice. For each ward, we identified all patients who died from cancer in the 3
      months before randomisation (preintervention) and in the 6 months after the
      completion of the LCP-I training programme. The primary endpoint was the overall
      quality of care toolkit scale. Analysis was by intention to treat. This study is
      registered with ClinicalTrials.gov, number NCT01081899. FINDINGS: During the
      postintervention assessment, data were gathered for 308 patients who died from
      cancer (147 in LCP-I programme wards and 161 in control wards). 232 (75%) of 308
      family members were interviewed, 119 (81%) of 147 with relatives cared for in the
      LCP-I wards (mean cluster size 14.9 [range eight to 22]) and 113 (70%) of 161 in
      the control wards (14.1 [eight to 22]). After implementation of the LCP-I
      programme, no significant difference was noted in the distribution of the overall
      quality of care toolkit scores between the wards in which the LCP-I programme was
      implemented and the control wards (score 70.5 of 100 vs 63.0 of 100; cluster
      adjusted mean difference 7.6 [95% CI -3.6 to 18.7]; p=0.186). INTERPRETATION: The
      effect of the LCP-I programme in our study is less than the effects noted in
      earlier phase 2 trials. However, if the programme is implemented well it has the
      potential to reduce the gap in quality of care between hospices and hospitals.
      Further research is needed to ascertain what components of the LCP-I programme
      might be effective and to develop and assess a wider range of approaches to
      quality improvement in hospital care for people at the end of their lives and for
      their families. FUNDING: Italian Ministry of Health and Maruzza Lefebvre D'Ovidio
      Foundation-Onlus.

PMID- 24139709
TI  - Accelerometer-determined physical activity and walking capacity in persons with
      Down syndrome, Williams syndrome and Prader-Willi syndrome.
AB  - In this study we describe by use of accelerometers the total physical activity
      (PA), intensity pattern and walking capacity in 87 persons age 16-45 years with
      Down syndrome (DS), Williams syndrome (WS) and Prader-Willi syndrome (PWS).
      Participants were recruited from all over Norway, and lived either with their
      parents or in community residences with support. On average the participants
      generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day
      spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71
      min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical
      activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic
      recommendations for PA. When compared, no differences for total physical activity
      or time in MVPA were observed between the three groups. However, participant with
      DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities
      compared to participants with PWS and WS, respectively, (p=0.011, 95% CI: -10.9; 
      80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than
      the PWS-group and 41 min/day more than the WS-group, (p<0.001, 95% CI: 29.3;
      79.7). Participants with PWS spent on average 30 min/day less in lifestyle
      activities compared to both participants with DS and WS, (p<0.001, 95% CI: -14.2;
      -45.4). No association between total PA and BMI were observed. Males were more
      active than females across all diagnoses. Males accumulated on average 85 counts
      per minutes more than females, (p=0.002, 95% CI: 33.3; 136.7), 2137 more steps
      per day, (p=0.002, 95% CI: 778; 3496). The mean walking capacity during six
      minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance
      walked during testing decreased with 33.6 m when comparing normal or underweight
      participants to overweight participants, and 78.1 m when comparing overweight to
      obese participants (p<0.001 95% CI: -40.4; -85.8). When adjusted for BMI no
      differences in walking capacity between the three genetic conditions were
      observed.

PMID- 24139710
TI  - Assisting people with disabilities in actively performing physical activities by
      controlling the preferred environmental stimulation with a gyration air mouse.
AB  - The latest researchers have employed software technology to turn gyration air
      mice into a high performance limb detector to detect specific limb movement, and
      to further collaborate using the preferred environmental stimulation to help
      people with disabilities to suppress unwanted behaviors or habits and to reward
      good behaviors. This study extended the functionality of a gyration air mouse,
      and used the mouse as a precise physical activity detector integrated with the
      preferred environmental stimulation to assess if this integrated set can be used
      to help two disabled people who are overweight and lacking in exercise to
      actively perform physical activities. The study was conducted based on an A-B-A-B
      design. The results showed that both participants increased significantly the
      time duration required for them to maintain their physical activity status so
      that they could obtain their favorite environmental stimulation during the
      intervention phases. Both the practical and developmental implications of the
      findings are then discussed. 

PMID- 24139711
TI  - Caregivers' reported functional limitations in activities of daily living among
      middle-aged adults with intellectual disabilities.
AB  - This study was conducted to describe the functioning of Activities of Daily
      Living (ADL) and to examine socio-economic effects on ADL functioning among
      adults with intellectual disabilities (ID) aged 45 years and older (N=480) in
      Taiwan. The Barthel Index (BI) was used to determine a baseline level of ADL
      functioning in the study participants. There are five categories of functional
      impairment using the following cut-off values in Taiwan: total dependence (BI
      score 0-20), severe (BI score 21-60), moderate (BI score 61-90), mild (BI score
      91-99), and total independence (BI score 100) (Taiwan Department of Health,
      2012). The results revealed that 2.3% of adults with ID were in total dependence,
      11.9% were in severe dependence, 27.9% were in moderate dependence, 8.1% had a
      mild dependence, and 49.8% were totally independent. In the multiple linear
      regression model of the ADL score, we determined that educational level, comorbid
      Down's syndrome, and disability level are the variables able to significantly
      predict ADL score (R(2)=0.190) after controlling for the factors of age, marital
      status, and other comorbidity conditions. Those ID adults with a lower education
      level (primary vs. literate, beta=4.780, p=0.031; intermediate vs. literate,
      beta=6.642, p=0.030), with comorbid Down's syndrome (beta=-7.135, p=0.063), and
      with a more severe disability condition (severe vs. mild, beta=-7.650, p=0.007;
      profound vs. mild, beta=-19.169, p<0.001) had significantly lower ADL scores. The
      present study highlights the need to support mobility in older adults with ID as
      much as possible to optimize independence in this group. 

PMID- 24139712
TI  - Looking and thinking: how individuals with Williams syndrome make judgements
      about mental states.
AB  - Individuals with the neuro-developmental disorder Williams syndrome (WS) are
      characterised by a combination of features which makes this group vulnerable
      socially, including mild-moderate cognitive difficulties, pro-social drive, and
      indiscriminate trust. The purpose of this study was to explore a key socio
      communicative skill in individuals with WS, namely, mental state recognition
      abilities. We explored this skill in a detailed way by looking at how well
      individuals with WS recognise complex everyday mental states, and how they
      allocate their attention while making these judgements. Participants with WS were
      matched to two typically developing groups for comparison purposes, a verbal
      ability matched group and a chronological age matched group. While eye movements
      were recorded, participants were shown displays of eight different mental states
      in static and dynamic form, and they performed a forced-choice judgement on the
      mental state. Mental states were easier to recognise in dynamic form rather than
      static form. Mental state recognition ability for individuals with WS was poorer
      than expected by their chronological age, and at the level expected by their
      verbal ability. However, the pattern of mental state recognition for participants
      with WS varied according to mental state, and we found some interesting links
      between ease/difficulty recognising some mental states (worried/do not trust) and
      the classic behavioural profile associated with WS (high anxiety/indiscriminate
      trust). Furthermore, eye tracking data revealed that participants with WS
      allocated their attention atypically, with less time spent attending the
      information from the face regions. This challenges the widely held understanding
      of WS being associated with prolonged face and eye gaze, and indicates that there
      is more heterogeneity within this disorder in terms of socio-perception than
      previous reports would suggest. 

PMID- 24139713
TI  - Neuromuscular fatigue during high-intensity intermittent exercise in individuals
      with intellectual disability.
AB  - This study examined neuromuscular fatigue after high-intensity intermittent
      exercise in 10 men with mild intellectual disability (ID) in comparison with 10
      controls. Both groups performed three maximal voluntary contractions (MVC) of
      knee extension with 5 min in-between. The highest level achieved was selected as
      reference MVC. The fatiguing exercise consists of five sets with a maximal number
      of flexion-extension cycles at 80% of the one maximal repetition (1RM) for the
      right leg at 90 degrees  with 90 s rest interval between sets. The MVC was tested
      again after the last set. Peak force and electromyography (EMG) signals were
      measured during the MVC tests. Root Mean Square (RMS) and Median Frequency (MF)
      were calculated. Neuromuscular efficiency (NME) was calculated as the ratio of
      peak force to the RMS. Before exercise, individuals with ID had a lower MVC
      (p<0.05) and a lower RMS (p<0.05). No significant difference between groups in MF
      and NME. After exercise, MVC decreases significantly in both groups (p<0.001).
      Individuals with ID have greater force decline (p<0.001 vs. p<0.01). RMS
      decreased significantly (p<0.001) whereas the NME increased significantly
      (p<0.05) in individuals with ID, but both remained unchanged in controls. The MF
      decreased significantly in both groups (p<0.001). In conclusion, individuals with
      ID presented a lower peak force than individuals without ID. After a high
      intensity intermittent exercise, individuals with ID demonstrated a greater force
      decline caused by neural activation failure. When rehabilitation and sport train
      ID individuals, they should consider this nervous system weakness.

PMID- 24139714
TI  - Signal-to-noise velocity peaks difference: a new method for evaluating the
      handwriting movement fluency in children with dysgraphia.
AB  - This study evaluated handwriting movement dysfluency related to dysgraphia. A new
      variable, the Signal-to-Noise velocity peaks difference (SNvpd), was proposed to
      describe abnormal velocity fluctuations in cursive handwriting. This variable was
      compared to two variables most frequently used variables for assessing
      handwriting fluency. This comparison was carried out for three different groups,
      children with dysgraphia, proficient children, and adults, all of whom wrote the
      same single word. The adults were taken as the reference. Results revealed that,
      of the three variables studied, the SNvpd proved most efficient in discriminating
      children with dysgraphia, and that furthermore, it had the significant advantage
      of facilitating the localization of dysfluency peaks within a word. Our results
      also showed that the movement dysfluency of children with dysgraphia was specific
      to certain letters. In light of these results, we discuss the methodological and
      theoretical relevance of this new variable to the analysis of handwriting
      movement with the aim of characterizing dysgraphia. 

PMID- 24139715
TI  - Problem solving ability in children with intellectual disability as measured by
      the Raven's colored progressive matrices.
AB  - This study investigated the developmental trajectory of problem solving ability
      in children with intellectual disability (ID) of different etiologies (Down
      Syndrome, Idiopathic ID or low functioning Autism) as measured on the Raven's
      Colored Progressive Matrices test (RCPM). Children with typical development (TD)
      and children with ID were matched on total correct performance (i.e., non-verbal
      mental age) on the RCPM. RCPM total correct performance and the sophistication of
      error types were found to be associated with receptive vocabulary in all
      participants, suggesting that verbal ability plays a role in more sophisticated
      problem solving tasks. Children with ID made similar errors on the RCPM as
      younger children with TD as well as more positional error types. This result
      suggests that children with ID who are deficient in their cognitive processing
      resort to developmentally immature problem solving strategies when unable to
      determine the correct answer. Overall, the findings support the use of RCPM as a
      valid means of matching intellectual capacity of children with TD and ID. 

PMID- 24139716
TI  - Comparisons of intervention components within augmentative and alternative
      communication systems for individuals with developmental disabilities: a review
      of the literature.
AB  - Decisions regarding augmentative and alternative communication (AAC) for
      individuals with developmental disabilities (e.g. what AAC to use and how to
      teach a person to use a specific AAC modality) should involve consideration of
      different intervention component options. In an effort to elucidate such
      decisions and options, this review synthesized 14 studies, published between 2004
      and 2012, comparing different AAC intervention components including different
      symbol sets, instructional strategies, or speech output within aided AAC systems,
      and different verbal operants within unaided AAC. Evidence supported the
      following: (a) different instructional strategies such as building motivation,
      using errorless learning, or adding video models to picture exchange
      interventions may improve the acquisition or rate of acquisition of picture
      exchange mands, (b) limited data supports training mimetic (imitated) or mand
      signs over tacts and (c) differences in symbol sets and speech output levels
      appeared to have little effect on AAC-based mand acquisition, but listener-based
      differences should be considered. These findings have implications for future
      research and clinical practice. 

PMID- 24139717
TI  - Development of social functioning and communication in school-aged (5-9 years)
      children with cerebral palsy.
AB  - The aim of this study was to examine determinants of the course and level of
      social functioning and communication in school-aged children with cerebral palsy
      (CP) over a 2-year period. A clinic-based sample of 5 and 7 years old children
      with CP (n=108; 72 males; mean age 6 y 3 mo, SD 12 mo; Gross Motor Function
      Classification System (GFMCS) level I-V) was followed longitudinally in three
      yearly assessments. Social functioning and communication were measured with the
      Vineland Adaptive Behavior Scales (VABS). Data were analyzed with generalized
      estimated equations. The results showed that social function followed a course of
      progressive restrictions over time in non-ambulatory children with CP aged 5-9
      compared to children who could walk with or without walking aids. Overall lower
      levels of social functioning were found in children with GMFCS V, epilepsy,
      speech problems, lower intellectual capacity and older age at baseline. For
      communication more restrictions over time were found in children with lower
      intellectual capacity. Children with GMFCS V, speech problems and older age at
      baseline had overall greater restrictions in communication. It was concluded that
      motor functioning and intellectual ability can be used to identify children at
      risk for progressive restrictions in social functioning and communication. For
      children with CP and social and communicative restrictions, multidisciplinary
      assessment and treatment may be indicated to counteract an unfavorable
      development.

PMID- 24139718
TI  - Do students with Down syndrome have a specific learning profile for reading?
AB  - The present study assessed achieved reading stages of 190 school-aged children
      with Down syndrome (DS, age 6-20) in Bavaria, one of the most populated federal
      states in Germany. Teachers described the reading stages of their students in a
      questionnaire. The achieved stages of reading according to the developmental
      model of Frith are compared to a sample of 1419 students with intellectual
      disability (ID) regardless of etiology, but excluding DS; thereafter parallelized
      ID-groups were compared. Results of the questionnaire addressed to the students'
      teachers showed that 20.2% of the students with DS do not read at all, 7.6% read
      at a logographic stage, 49.4% at an alphabetic and 22.8% at an orthographic
      level. Alongside these findings among the whole sample, correlations are
      described concerning age, gender, IQ and sociocultural background. The students
      with DS are then compared to other students with ID with mixed etiologies. This
      comparison stresses the emphasis on the alphabetic level amongst students with
      DS. This emphasis also exists when DS and non-DS students are parallelized in
      groups of ID, thus showing that students with DS and severe ID are ahead in
      reading, but those with mild ID are behind. Knowledge about specific literacy
      attainment of students with DS is vital for planning instruction, for creating
      learning environments, and for formulating future fields of research. Especially
      students with DS need specific teaching which takes their impaired verbal short
      term memory into account, such as learning to read in syllables. 

PMID- 24139719
TI  - Molecular typing of fowl adenoviruses, isolated in Hungary recently, reveals high
      diversity.
AB  - Molecular typing of 26 recent fowl adenovirus (FAdV) isolates obtained in Eastern
      Hungary between 2006 and 2011 was performed. The viruses were isolated on primary
      chicken embryo liver cell cultures from carcasses of chickens, sent for
      diagnostic investigation. The isolates were subjected to a PCR to amplify a
      fragment from the hexon gene. Sequence analysis of the amplicons revealed the
      presence of all the five FAdV species in the country, among them FAdV-B, which
      has been barely found in Hungary before. The three strains classified as FAdV-B
      might represent a novel type within this species, as their nucleotide sequence
      identity to strain 340 (type FAdV-5) is below the commonly accepted intratype
      limit. Most of the strains (63%) were classified into species FAdV-E (12 strains)
      and FAdV-D (7 strains) in the study. Four of the isolates proved to be the
      mixture of two adenovirus strains belonging to two different FAdV types, in three
      from these four cases, these two types even belonged to two different species.
      Analysing the pathological findings bolsters certain established connections
      between some FAdV types and disease conditions. Gizzard erosion was found in
      connection with FAdV-1 strains only, and inclusion body hepatitis with FAdV-D and
      -E strains. 

PMID- 24139720
TI  - Development of a single multi-locus sequence typing scheme for Taylorella
      equigenitalis and Taylorella asinigenitalis.
AB  - We describe here the development of a multilocus sequence typing (MLST) scheme
      for Taylorella equigenitalis, the causative agent of contagious equine metritis
      (CEM), and Taylorella asinigenitalis, a nonpathogenic bacterium. MLST was
      performed on a set of 163 strains collected in several countries over 35 years
      (1977-2012). The MLST data were analyzed using START2, MEGA 5.05 and eBURST, and
      can be accessed at http://pubmlst.org/taylorella/. Our results revealed a clonal
      population with 39 sequence types (ST) and no common ST between the two
      Taylorella species. The eBURST analysis grouped the 27 T. equigenitalis STs into
      four clonal complexes (CC1-4) and five unlinked STs. The 12 T. asinigenitalis STs
      were grouped into three clonal complexes (CC5-7) and five unlinked STs, among
      which CC1 (68.1% of the 113 T. equigenitalis) and CC5 (58.0% of the 50 T.
      asinigenitalis) were dominants. The CC1, still in circulation in France, contains
      isolates from the first CEM outbreaks that simultaneously emerged in several
      countries in the late 1970s. The emergence in different countries (e.g. France,
      Japan, and United Arab Emirates) of STs without any genetic relationship to CC1
      suggests the existence of a natural worldwide reservoir that remains to be
      identified. T. asinigenitalis appears to behave same way since the American,
      Swedish and French isolates have unrelated STs. This first Taylorella sp. MLST is
      a powerful tool for further epidemiological investigations and population biology
      studies of the Taylorella genus. 

PMID- 24139721
TI  - Antigenic analysis of H5N1 highly pathogenic avian influenza viruses circulating
      in Egypt (2006-2012).
AB  - The highly pathogenic avian influenza (HPAI) H5N1 in Egypt circulated
      continuously after its introduction in February 2006 with substantial economic
      losses and frequent human infections. Phylogenetic analysis of the available HA
      sequences revealed the presence of two main sublineages; the classic 2.2.1 and
      the variant 2.2.1.1. The classic 2.2.1 had subdivided into two clusters of
      viruses; cluster C1 contained the originally introduced virus and isolates from
      2006 to 2009 and cluster C2 emerged in 2007 and continues to circulate. The
      variant 2.2.1.1 represents the isolates mainly from chickens and subdivided into
      two clusters; cluster V1 contains isolates from 2007 to 2009 and cluster V2
      contains isolates from 2008 to 2011. Sequence analysis revealed 28 amino acid
      mutations in the previously reported antigenic sites and high evolution rate
      which may be due to selective pressure from vaccination and/or natural infection.
      Antigenic analysis of 18 H5N1 isolates from 2006 to 2012 that represent different
      clusters was conducted using hemagglutination inhibition (HI) and virus
      neutralization (VN) assays using hyperimmune sera produced by immunizing SPF
      chickens with inactivated whole-virus. Antigenic relatedness of ancestral
      Egyptian H5N1 isolate (459-3/06) with other isolates ranged from 30.7% to 79.1%
      indicating significant antigenic drift of the H5N1 viruses from the ancestral
      strains. The antigenic relatedness between C2 and V2 clusters ranged from 28.9%
      to 68% supporting the need for vaccine seed strains from both clusters.
      Interestingly, A/CK/EG/1709-6/2008 H5N1 strain showed a broad cross reactivity
      against viruses in different H5N1 clusters (antigenic relatedness ranged from
      63.9% to 85.8%) demonstrating a potential candidate as a vaccine strain.
      Antigenic cartography which facilitates a quantitative interpretation and easy
      visualization of serological data was constructed based on HI results and further
      demonstrated the several antigenic groups among Egyptian H5N1 viruses. In
      conclusion, the cross reactivity between the co-circulating H5N1 strains may not
      be adequate for protection against each other and it is recommended to test
      vaccines that contain isolates from different antigenic groups in experimental
      infection trials for the selection of vaccine seed strain. Furthermore, the
      continuous monitoring for detecting the emerging variants followed by detailed
      antigenic analysis for updating vaccines is warranted. 

PMID- 24139722
TI  - Characterisation of a catalase-negative methicillin-resistant Staphylococcus
      aureus isolate from a dog.
AB  - A catalase-negative MRSA strain and a methicillin resistant Staphylococcus
      pseudintermedius strain (MRSP) were isolated from a dog affected by a severe form
      of pododermatitis. The catalase negative isolate was typed as SCCmec I, PVL
      negative, ST5 t002 strain. A deletion at position 487 of the kat gene altered the
      functionality of the catalase enzyme. This is the first report of a catalase
      negative MRSA in animals. As catalase test is a rapid assay routinely employed
      for the identification of staphylococci in clinical microbiology laboratories,
      the presence of MRSA with this uncommon phenotype may be underestimated.
      Moreover, catalase-negative staphylococci should be investigated more in-depth in
      order to assess their virulence. 

PMID- 24139723
TI  - An explanation of why schizophrenia begins with excitotoxic damage to the
      hippocampus.
AB  - A recent paper by Schobel et al. provides evidence that schizophrenia begins with
      excitotoxic damage in the hippocampus, primarily in the CA1 subfield. MRI
      measurement of cerebral blood volume (CBV) was taken to be a marker of basal
      metabolism. High baseline CBV in the CA1 subfield of subjects at high risk for
      schizophrenia predicted progression to psychosis and the development of
      hippocampal atrophy. A mouse model of ketamine excitotoxicity reproduced the
      human imaging study, i.e. hypermetabolism in CA1 led to atrophy. The authors do
      not explain the pathophysiology of selective excitotoxicity in the hippocampus. A
      recently published serotonin theory of schizophrenia provides a hypothetical
      explanation for these findings. The serotonin theory predicts that schizophrenia
      begins with stress-induced overdrive of serotonergic pacemaker cells in the
      dorsal raphe nucleus. The overdrive is passed via the entorhinal cortex to the
      hippocampus, where it causes excitotoxicity. Passage through the entorhinal
      cortex converts a serotonergic signal into a glutamate signal, glutamate being
      the neurotransmitter of exicitotoxicity. The remitting-relapsing pattern of
      schizophrenia is explained by a balance between excitotoxicity in the hippocampus
      and repopulation by neurogenesis in the subgranular zone. Injury is balanced by
      healing. 

PMID- 24139724
TI  - Evaluating camouflage design using eye movement data.
AB  - This study investigates the characteristics of eye movements during a camouflaged
      target search task. Camouflaged targets were randomly presented on two natural
      landscapes. The performance of each camouflage design was assessed by target
      detection hit rate, detection time, number of fixations on display, first saccade
      amplitude to target, number of fixations on target, fixation duration on target,
      and subjective ratings of search task difficulty. The results showed that the
      camouflage patterns could significantly affect the eye-movement behavior,
      especially first saccade amplitude and fixation duration, and the findings could
      be used to increase the sensitivity of the camouflage assessment. We hypothesized
      that the assessment could be made with regard to the differences in detectability
      and discriminability of the camouflage patterns. These could explain less
      efficient search behavior in eye movements. Overall, data obtained from eye
      movements can be used to significantly enhance the interpretation of the effects
      of different camouflage design. 

PMID- 24139725
TI  - Sleep duration and hypertension: flawed methods call the conclusions into
      question.

PMID- 24139726
TI  - Neurobiologic basis of craving for carbohydrates.
AB  - OBJECTIVES: There is a relationship between emotional disorders, obesity, and
      craving for carbohydrates. This relationship complicates the success of
      treatments aimed at combatting obesity, which is considered to be the epidemic of
      the twenty-first century. We conducted a review of the neurobiologic basis for
      carbohydrate craving, with the hope that this understanding will enable the
      design of more efficient therapeutic strategies. METHOD: We conducted a non
      systematic literature search in PubMed using MeSH. RESULTS: Research on the basis
      of carbohydrate craving is varied, but may be grouped into five main areas: the
      serotonergic system, palatability and hedonic response, the motivational system,
      stress response systems, and gene-environment interaction. CONCLUSIONS: The
      models that integrate motivational systems with palatability and hedonic response
      studies are the ones that we believe can best explain both craving for
      carbohydrates and related addictive phenomena. Research has contributed to a
      greater understanding of the neurobiologic basis of carbohydrate craving. The
      latter, in turn, contributes to an understanding of the implications, challenges,
      and possible therapies that might be put in place to cope with this phenomenon.

PMID- 24139727
TI  - Association between chocolate consumption and fatness in European adolescents.
AB  - OBJECTIVE: There is a substantial interest in the potential role of chocolate in
      the prevention of cardiovascular diseases. It has been recently reported that a
      higher frequency of chocolate intake is linked to lower body mass index (BMI) in
      adults. The aim of the present study was to determine if higher chocolate
      consumption also is associated with lower BMI, as well as other markers of total
      and central body fat, in adolescents. METHODS: This study comprised 1458
      adolescents (ages 12.5-17.5 y) participating in HELENA-CSS (Healthy Lifestyle in
      Europe by Nutrition in Adolescence Cross-Sectional Study). Dietary intake was
      self-registered using a computer-based tool for 24-h dietary recall on 2 non
      consecutive days. Weight and height were measured, and BMI was calculated.
      Adiposity was estimated using skinfolds (Slaughter's equation) and bioelectrical
      impedance analysis (BIA). Waist circumference was measured. Sexual maturation
      also was recorded. Physical activity was measured by accelerometry. RESULTS:
      Higher chocolate consumption was associated with lower levels of total and
      central fatness, as estimated by BMI, body fat estimated from skinfolds and BIA,
      and waist circumference, regardless of potential confounders (P <= 0.01).
      CONCLUSION: Our results demonstrate that a higher chocolate consumption was
      associated with lower total and central fatness in European adolescents.

PMID- 24139728
TI  - Survey of mercury, cadmium and lead content of household batteries.
AB  - The objective of this work was to provide updated information on the development
      of the potential impact of heavy metal containing batteries on municipal waste
      and battery recycling processes following transposition of the new EU Batteries
      Directive 2006/66/EC. A representative sample of 146 different types of
      commercially available dry and button cells as well as lithium-ion accumulators
      for mobile phones were analysed for their mercury (Hg)-, cadmium (Cd)- and lead
      (Pb)-contents. The methods used for preparing the cells and analysing the heavy
      metals Hg, Cd, and Pb were either developed during a former study or newly
      developed. Several batteries contained higher mass fractions of mercury or
      cadmium than the EU limits. Only half of the batteries with mercury and/or lead
      fractions above the marking thresholds were labelled. Alkaline-manganese mono
      cells and Li-ion accumulators, on average, contained the lowest heavy metal
      concentrations, while zinc-carbon batteries, on average, contained the highest
      levels. 

PMID- 24139729
TI  - Wettability and bond strength between leucite-reinforced dental porcelains and Co
      Cr alloy.
AB  - STATEMENT OF PROBLEM: A series of methods has been used to evaluate metal ceramic
      bond strength. However, little attention has been paid to the wettability and
      interfacial reactions of dental porcelain/alloy systems, which may affect the
      bond strength of metal ceramic restorations. PURPOSE: The purpose of this study
      was to understand the wetting and spreading behaviors, the interfacial reactions,
      and the bonding mechanism of ceramic to metal with TiO2 and MoO3 added to the
      dental porcelain. MATERIAL AND METHODS: Two leucite-reinforced dental porcelains
      were used in the study. Twelve Co-Cr alloy sheets (15 * 10 * 2 mm) divided into 2
      groups were used to evaluate the wetting process, and 12 Co-Cr alloy sheets (25 *
      3 * 0.5 mm) (Bego) divided into 2 groups were used for the 3-point bond strength
      test. The wetting process of the porcelain/alloy systems was observed in situ
      with a Tommi optical dimension measurement system using a modified sessile drop
      method. The reaction products of the interfacial region were determined by Raman
      spectra analyses. Metal ceramic specimens were tested in 3-point bending at a
      crosshead speed of 1.5 mm/min according to ISO 9693 requirements, and the results
      were statistically analyzed with 1-way ANOVA (alpha=.05). RESULTS: The addition
      of TiO2 and MoO3 in the dental porcelain improved the wettability of the dental
      porcelain/Co-Cr alloy system. The bond strength of the porcelain modified with
      TiO2 and MoO3 was 43 +/-2 MPa and that of the unmodified porcelain was 38 +/-3
      MPa. The fracture of the 2 metal ceramic systems occurred near the porcelain
      layer. CONCLUSIONS: The application of TiO2 and MoO3 to the leucite-reinforced
      porcelain can improve the wettability of porcelain on alloy. Porcelain/alloy
      wettability can be used as a guide to improve the bonding property between dental
      porcelain and alloys.

PMID- 24139730
TI  - Management of mandibular rotation after a mandibulectomy: a clinical report.
AB  - Oral rehabilitation after a mandibulectomy is a challenge for prosthodontists.
      This clinical report describes the management of a 54-year-old man, who, after a
      mandibulectomy, had rotation of the mandible, with a revascularized flap,
      followed by an implant-supported prosthesis and ceramic restorations. 

PMID- 24139731
TI  - Clinical features and molecular genetics of two Tunisian families with
      abetalipoproteinemia.
AB  - Abetalipoproteinemia (ABL) is a rare monogenic disease characterized by very low
      plasma levels of cholesterol and triglyceride and almost complete absence of
      apolipoprotein B (apoB)-containing lipoproteins. Typically, patients present with
      failure to thrive, acanthocytosis, pigmented retinopathy and neurological
      features. It has been shown that ABL results from mutations in the gene encoding
      the microsomal triglyceride transfer protein (MTTP). Sanger sequencing of MTTP
      was performed for two unrelated consanguineous Tunisian families with two
      affected individuals each, presenting a more severe ABL phenotype than previously
      reported in the literature. The patients were found to be homozygous for two
      novel mutations. In the first family, a nonsense mutation, c.2313T>A, leading to
      a truncated protein (p.Y771X) was identified. In the second family, a splice
      mutation, IVS 9+2T>G, was found. These mutations are believed to abolish the
      assembly and secretion of apoB-containing lipoproteins. 

PMID- 24139732
TI  - Presacral extramedullary hematopoiesis: an alternative hypothesis.
AB  - Idiopathic extramedullary hematopoiesis (EMH) is the production of blood cells
      outside of the bone marrow without an underlying hematological pathology. This
      article examines the rare case of idiopathic EMH in the presacral area. A 65-year
      old woman with a past medical history of a total abdominal hysterectomy and a
      negative hematological history presented with back and leg pain. MRI revealed a
      presacral mass. Fine needle aspiration revealed a diagnosis of EMH. The patient
      was managed conservatively with serial imaging. We present this patient with rare
      idiopathic, presacral EMH and review the literature on this topic. The current
      pathophysiology suggests that sacral fractures release hematopoietic stem cells,
      which in turn replicate to form an EMH mass. This review suggests a second
      mechanism in which surgical manipulation of the uterine tissue releases
      mesenchymal stem cells. These cells differentiate into stromal tissue that
      interacts with multipotent hematopoietic stem cells in order to form an EMH mass.
      Thus, idiopathic, presacral EMH may develop from either bone fractures or
      surgical manipulation of the uterus. Management of these patients should include
      watchful waiting unless intractable pain, new-onset weakness, or bowel/bladder
      dysfunction develops. 

PMID- 24139733
TI  - A systematic review of current and emerging approaches in the field of larynx
      preservation.
AB  - Treatment options targeting laryngeal preservation include conservative surgery,
      concurrent chemo-radiotherapy, induction chemotherapy (IC) followed by
      radiotherapy (RT), and alternating chemo-radiation. The goal of this paper was to
      perform a systematic review of randomized clinical trials (RCTs) on current and
      emerging approaches in the field of larynx preservation. The search identified 36
      papers of which 27 did not fall within the inclusion criteria (i.e. non-RCTs). IC
      followed by RT has been shown to allow laryngeal preservation in about two-thirds
      of pts with locally advanced laryngeal or hypopharyngeal cancer without
      compromising survival. IC is regarded as the landmark treatment of non-surgical
      larynx preservation approaches. Concomitant and alternating chemoradiotherapy
      treatments are also acceptable in larynx preservation. 

PMID- 24139734
TI  - Three cases of cutaneous mucormycosis with Lichtheimia spp. (ex
      Absidia/Mycocladus) in ICU. Possible cross-transmission in an intensive care unit
      between 2 cases.
AB  - Mucormycoses are rare but emerging diseases with poor prognosis caused by
      ubiquitous fungi from the environment. In November 2008, our teaching hospital
      experienced three cutaneous mucormycosis due to Lichtheimia spp. (ex
      Absidia/Mycocladus) in the intensive care and orthopaedic units. Environmental
      and epidemiological investigations suggested a possible cross-transmission of L.
      ramosa between two patients in intensive care. This is the first report of
      possible person-to-person transmission of mucormycosis species. These cases show
      the ineffectiveness of hydro-alcoholic solutions against spores and underline the
      need to respect standard precautions to prevent fungi dissemination. 

PMID- 24139735
TI  - Meiotic adaptation to genome duplication in Arabidopsis arenosa.
AB  - Whole genome duplication (WGD) is a major factor in the evolution of
      multicellular eukaryotes, yet by doubling the number of homologs, WGD severely
      challenges reliable chromosome segregation, a process conserved across kingdoms.
      Despite this, numerous genome-duplicated (polyploid) species persist in nature,
      indicating early problems can be overcome. Little is known about which genes are
      involved--only one has been molecularly characterized. To gain new insights into
      the molecular basis of adaptation to polyploidy, we investigated genome-wide
      patterns of differentiation between natural diploids and tetraploids of
      Arabidopsis arenosa, an outcrossing relative of A. thaliana. We first show that
      diploids are not preadapted to polyploid meiosis. We then use a genome scanning
      approach to show that although polymorphism is extensively shared across ploidy
      levels, there is strong ploidy-specific differentiation in 39 regions spanning 44
      genes. These are discrete, mostly single-gene peaks of sharply elevated
      differentiation. Among these peaks are eight meiosis genes whose encoded proteins
      coordinate a specific subset of early meiotic functions, suggesting these genes
      comprise a polygenic solution to WGD-associated chromosome segregation
      challenges. Our findings indicate that even conserved meiotic processes can be
      capable of nimble evolutionary shifts when required.

PMID- 24139736
TI  - Live imaging of bicoid-dependent transcription in Drosophila embryos.
AB  - The early Drosophila embryo is an ideal model to understand the transcriptional
      regulation of well-defined patterns of gene expression in a developing organism.
      In this system, snapshots of transcription measurements obtained by RNA FISH on
      fixed samples cannot provide the temporal resolution needed to distinguish
      spatial heterogeneity from inherent noise. Here, we used the MS2-MCP system to
      visualize in living embryos nascent transcripts expressed from the canonical
      hunchback (hb) promoter under the control of Bicoid (Bcd). The hb-MS2 reporter is
      expressed as synchronously as endogenous hb in the anterior half of the embryo,
      but unlike hb it is also active in the posterior, though more heterogeneously and
      more transiently than in the anterior. The length and intensity of active
      transcription periods in the anterior are strongly reduced in absence of Bcd,
      whereas posterior ones are mostly Bcd independent. This posterior noisy signal
      decreases progressively through nuclear divisions, so that the MS2 reporter
      expression mimics the known anterior hb pattern at cellularization. We propose
      that the establishment of the hb pattern relies on Bcd-dependent lengthening of
      transcriptional activity periods in the anterior and may require two distinct
      repression mechanisms in the posterior.

PMID- 24139737
TI  - Temporal jitter of the BOLD signal reveals a reliable initial dip and improved
      spatial resolution.
AB  - fMRI, one of the most important noninvasive brain imaging methods, relies on the
      blood oxygen level-dependent (BOLD) signal, whose precise underpinnings are still
      not fully understood. It is a widespread assumption that the components of the
      hemodynamic response function (HRF) are fixed relative to each other in time,
      leading most studies as well as analysis tools to focus on trial-averaged
      responses, thus using or estimating a condition- or location-specific "canonical
      HRF". In the current study, we examined the nature of the variability of the BOLD
      response and asked in particular whether the positive BOLD peak is subject to
      trial-to-trial temporal jitter. Our results show that the positive peak of the
      stimulus-evoked BOLD signal exhibits a trial-to-trial temporal jitter on the
      order of seconds. Moreover, the trial-to-trial variability can be exploited to
      uncover the initial dip in the majority of voxels by pooling trial responses with
      large peak latencies. Initial dips exposed by this procedure possess higher
      spatial resolution compared to the positive BOLD signal in the human visual
      cortex. These findings allow for the reliable observation of fMRI signals that
      are physiologically closer to neural activity, leading to improvements in both
      temporal and spatial resolution.

PMID- 24139738
TI  - Quantitative imaging of transcription in living Drosophila embryos links
      polymerase activity to patterning.
AB  - Spatiotemporal patterns of gene expression are fundamental to every developmental
      program. The resulting macroscopic domains have been mainly characterized by
      their levels of gene products. However, the establishment of such patterns
      results from differences in the dynamics of microscopic events in individual
      cells such as transcription. It is unclear how these microscopic decisions lead
      to macroscopic patterns, as measurements in fixed tissue cannot access the
      underlying transcriptional dynamics. In vivo transcriptional dynamics have long
      been approached in single-celled organisms, but never in a multicellular
      developmental context. Here, we directly address how boundaries of gene
      expression emerge in the Drosophila embryo by measuring the absolute number of
      actively transcribing polymerases in real time in individual nuclei.
      Specifically, we show that the formation of a boundary cannot be quantitatively
      explained by the rate of mRNA production in each cell, but instead requires
      amplification of the dynamic range of the expression boundary. This amplification
      is accomplished by nuclei randomly adopting active or inactive states of
      transcription, leading to a collective effect where the fraction of active nuclei
      is modulated in space. Thus, developmental patterns are not just the consequence
      of reproducible transcriptional dynamics in individual nuclei, but are the result
      of averaging expression over space and time.

PMID- 24139739
TI  - Spatiotemporal structure of REM sleep twitching reveals developmental origins of
      motor synergies.
AB  - BACKGROUND: During active (or REM) sleep, infant mammals exhibit myoclonic
      twitches of skeletal muscles throughout the body, generating jerky, discrete
      movements of the distal limbs. Hundreds of thousands of limb twitches are
      produced daily, and sensory feedback from these movements is a substantial driver
      of infant brain activity, suggesting that they contribute to motor learning and
      sensorimotor integration. It is not known whether the production of twitches is
      random or spatiotemporally structured, or whether the patterning of twitching
      changes with age; such information is critical for understanding how twitches
      contribute to development. RESULTS: We used high-speed videography and 3D motion
      tracking to assess the spatiotemporal structure of twitching at forelimb joints
      in 2- and 8-day-old rats. At both ages, twitches exhibited highly structured
      spatiotemporal properties at multiple timescales, including synergistic and
      multijoint movements within and across forelimbs. Hierarchical cluster analysis
      and latent class analysis revealed developmental changes in twitching quantity
      and patterning. Critically, we found evidence for a selectionist process whereby
      movement patterns at the early age compete for retention and expression over
      development. CONCLUSIONS: These findings indicate that twitches are not produced
      randomly but are highly structured at multiple timescales. This structure has
      important implications for understanding brain and spinal mechanisms that produce
      twitching, and the role that sensory feedback from twitching plays in
      sensorimotor system development. We propose that twitches represent a heretofore
      overlooked form of motor exploration that helps animals probe the biomechanics of
      their limbs, build motor synergies, and lay a foundation for complex, automatic,
      and goal-directed wake movements.

PMID- 24139740
TI  - Coupled oscillator dynamics of vocal turn-taking in monkeys.
AB  - Cooperation is central to human communication. The foundation of cooperative
      verbal communication is taking turns to speak. Given the universality of turn
      taking, it is natural to ask how it evolved. We used marmoset monkeys to explore
      whether another primate species exhibits cooperative vocal communication by
      taking turns. Marmosets share with humans a cooperative breeding strategy and
      volubility. Cooperative care behaviors are thought to scaffold prosocial
      cognitive processes. Moreover, marmosets and other callitrichid primates are very
      vocal and readily exchange vocalizations with conspecifics. By measuring the
      natural statistics of marmoset vocal exchanges, we observed that they take turns
      in extended sequences and show that this vocal turn-taking has as its foundation
      dynamics characteristic of coupled oscillators--one that is similar to the
      dynamics proposed for human conversational turn-taking. As marmoset monkeys are
      on a different branch of the evolutionary tree that led to humans, our data
      demonstrate convergent evolution of vocal cooperation. Perhaps more importantly,
      our data offer a plausible alternative scenario to "gestural origin" hypotheses
      for how human cooperative vocal communication could have evolved.

PMID- 24139741
TI  - Evidence for sex and recombination in the choanoflagellate Salpingoeca rosetta.
AB  - Nearly all animals reproduce sexually through the production and fusion of sperm
      and egg cells, yet little is known about the ancestry of animal sexual
      reproduction. Moreover, the sexual cycle of the closest living relatives of
      animals, the choanoflagellates, remains completely unknown. The choanoflagellate
      Monosiga brevicollis possesses a "meiotic toolkit" of genes, but the lack of
      polymorphisms detected during genome sequencing precluded inferences about its
      ploidy or sexual cycle. Here, we report that a related choanoflagellate,
      Salpingoeca rosetta, has a sexual life cycle and transitions between haploid and
      diploid states. Haploid cultures of S. rosetta became diploid in response to
      nutrient limitation. This ploidy shift coincided with anisogamous mating, during
      which small flagellated cells fused with larger flagellated cells. Distributions
      of polymorphisms in laboratory strains of S. rosetta provided independent
      evidence of historical recombination and mating. The ability of S. rosetta to
      produce morphologically differentiated gametes and to engage in sexual
      reproduction has implications for both reconstructing the evolution of sex in the
      progenitors of animals and establishing classical genetics in choanoflagellates.

PMID- 24139742
TI  - Distinct roles of the cortical layers of area V1 in figure-ground segregation.
AB  - BACKGROUND: What roles do the different cortical layers play in visual
      processing? We recorded simultaneously from all layers of the primary visual
      cortex while monkeys performed a figure-ground segregation task. This task can be
      divided into different subprocesses that are thought to engage feedforward,
      horizontal, and feedback processes at different time points. These different
      connection types have different patterns of laminar terminations in V1 and can
      therefore be distinguished with laminar recordings. RESULTS: We found that the
      visual response started 40 ms after stimulus presentation in layers 4 and 6,
      which are targets of feedforward connections from the lateral geniculate nucleus
      and distribute activity to the other layers. Boundary detection started shortly
      after the visual response. In this phase, boundaries of the figure induced
      synaptic currents and stronger neuronal responses in upper layer 4 and the
      superficial layers ~70 ms after stimulus onset, consistent with the hypothesis
      that they are detected by horizontal connections. In the next phase, ~30 ms
      later, synaptic inputs arrived in layers 1, 2, and 5 that receive feedback from
      higher visual areas, which caused the filling in of the representation of the
      entire figure with enhanced neuronal activity. CONCLUSIONS: The present results
      reveal unique contributions of the different cortical layers to the formation of
      a visual percept. This new blueprint of laminar processing may generalize to
      other tasks and to other areas of the cerebral cortex, where the layers are
      likely to have roles similar to those in area V1.

PMID- 24139743
TI  - Aplacophoran mollusks evolved from ancestors with polyplacophoran-like features.
AB  - Mollusca is an animal phylum with vast morphological diversity and includes worm
      shaped aplacophorans, snails, bivalves, and the complex cephalopods. The
      interrelationships of these class-level taxa are still contentious, but recent
      phylogenomic analyses suggest a dichotomy at the base of Mollusca, resulting in a
      monophyletic Aculifera (comprising the shell-less, sclerite-bearing aplacophorans
      and the eight-shelled polyplacophorans) and Conchifera (all other, primarily
      univalved groups). The Aculifera concept has recently gained support via
      description of the fossil Kulindroplax, which shows both aplacophoran- and
      polyplacophoran-like features and suggests that the aplacophorans originated from
      a shelled ancestor, but the overall morphology of the last common aculiferan
      ancestor remains obscure. Here we show that larvae of the aplacophoran Wirenia
      argentea have several sets of muscles previously known only from polyplacophoran
      mollusks. Most of these are lost during metamorphosis, and we interpret them as
      ontogenetic remnants of an ancestor with a complex, polyplacophoran-like
      musculature. Moreover, we find that the first seven pairs of dorsoventral muscles
      develop synchronously in Wirenia, similar to juvenile polyplacophorans, which
      supports the conclusions based on the seven-shelled Kulindroplax. Accordingly, we
      argue that the simple body plan of recent aplacophorans is the result of
      simplification and does not represent a basal molluscan condition.

PMID- 24139744
TI  - Nutcracker syndrome--how well do we know it?
AB  - Nutcracker syndrome (NCS), which is caused by compression of the left renal vein
      between the abdominal aorta and the superior mesenteric artery, leads to a series
      of clinical symptoms including hematuria, proteinuria, flank pain, and
      varicocele. The diagnosis of NCS is difficult due to variations in normal
      anatomy. Treatment, which ranges from observation to nephrectomy, remains
      controversial. We conducted a review based on the related literature and our
      experience with hundreds of cases. We summarize the characteristics of NCS, the
      different measurements used in diagnosis, and the current treatment options. We
      present our diagnostic criteria and recommend endovascular stenting as the
      primary option for NCS. 

PMID- 24139745
TI  - Shortened pubic bones in bladder exstrophy: a congenital or acquired phenomenon?
AB  - OBJECTIVE: It is accepted that the length of the anterior segment of the pelvis
      in classic bladder exstrophy is shorter than that of controls. However, studies
      performed involve children with a wide range of ages. By studying children with
      classic bladder exstrophy under the age of 1 year, the authors aim to ascertain
      if there is a congenital pubic bone length discrepancy associated with bladder
      exstrophy. MATERIAL AND METHODS: Fourteen classic bladder exstrophy patients
      under 1 year of age and 14 age-matched controls were identified. Three
      dimensional (3D) computerized tomography was used to measure the length of the
      superior pubic ramus bilaterally. In the exstrophy group, scans were performed
      before bladder closure. The Mann-Whitney U test was used and p < 0.05 was
      considered significant. RESULTS: There was no significant difference (p = 0.76)
      in the median age in cases (72 days) and controls (64 days). The median superior
      pubic ramus length was 19.1 mm in the exstrophy group and 20 mm in the control
      group (p = 0.99). CONCLUSIONS: Superior pubic ramus length in children under 1
      year of age with classic bladder exstrophy is not statistically different from
      that in control subjects. Therefore, the authors hypothesize that the previously
      described shortening of the pubic bones is an acquired phenomenon, which may
      develop after the first year of life.

PMID- 24139746
TI  - Hip fracture and anthropometric variations: dominance among trochanteric soft
      tissue thickness, body height and body weight during sideways fall.
AB  - BACKGROUND: Hip fracture depends on various anthropometric parameters such as
      trochanteric soft tissue thickness, body height and body weight. The objective
      was to evaluate the responses to the variations in anthropometric parameters
      during sideways fall, and to identify the most dominant parameter among them.
      METHOD: Seven finite element models were developed having anthropometric
      variations in trochanteric soft tissue thickness (5-26 mm), body height (1.70
      1.88 m), and body weight (63-93.37 kg). These were simulated for sideways fall
      with ANSYS-LS-DYNA(r) code. FINDINGS: Significant effect of trochanteric soft
      tissue thickness variation was found on 'normalized peak impact force with
      respect to the body weight' (p=0.004, r2=0.808) and strain ratio (p=0.083,
      r2=0.829). But, variation in body height was found to be less significant on
      normalized peak impact force (p=0.478, r2=0.105) and strain ratio (p=0.292,
      r2=0.217). Same was true for the variation in body weight on normalized peak
      impact force (p=0.075, r2=0.456) and strain ratio (p=0.857, r2=0.007). The risk
      factor for fracture was also well correlated to the strain ratio for the inter
      trochanteric zone (p<0.0007, r2=0.917) where the most fractures are clinically
      observed to happen. INTERPRETATIONS: Trochanteric soft tissue thickness was found
      likely to be the most dominant parameter over body height and body weight,
      signifying that a slimmer elderly person, taller or shorter, with less
      trochanteric soft tissue thickness should be advised to take preventive measures
      against hip fracture under sideways fall.

PMID- 24139747
TI  - Spontaneous pneumomediastinum in a patient with diabetic ketoacidosis.

PMID- 24139748
TI  - Geographic mobility of Korean new graduate nurses from their first to subsequent
      jobs and metropolitan-nonmetropolitan differences in their job satisfaction.
AB  - BACKGROUND: Nurses are known to migrate from rural to urban areas, which may
      cause geographic imbalances in the workforce. PURPOSE: The aim of this study was
      to compare new graduate nurse retention based on the type of geographic area
      (capital, metropolitan, and nonmetropolitan) of their first job and their job
      satisfaction by geographic location. METHODS: The sample included 533 nursing
      graduates working full-time as registered nurses in hospitals or clinics.
      Survival analysis was conducted to compare nurse retention in three geographic
      locations. RESULTS: Survival curves for nurses in capital and nonmetropolitan
      areas were significantly different. The 1-, 2-, and 3-year survival probabilities
      of nurses in the capital were .923, .881, and .872, respectively, whereas those
      in nonmetropolitan areas were .887, .776, and .672, respectively. Nurses in
      nonmetropolitan areas were more dissatisfied with pay (odd ratio [OR] = 1.820, p
      = .009), fringe benefits (OR =1.893, p = .015), employment security (OR =2.640, p
      = .033), and personal growth (OR =1.626, p = .045) than those in the capital.
      CONCLUSIONS: Nurses employed in nonmetropolitan areas were more mobile and less
      satisfied with their jobs than those in the capital.

PMID- 24139749
TI  - Inflammatory bowel disease and the risk of osteoporosis and fracture.
AB  - Inflammatory bowel disease (IBD) is commonly believed to increase the risk of
      bone mineral loss, leading to osteoporosis and an increased risk of disabling
      fractures. In this narrative review, we will presenting a summary of the
      published medical literature in regards to the relationship between IBD and the
      development of osteoporosis, bone mineral loss, and fractures. We will explore
      the epidemiology of metabolic bone disease in IBD, focusing on the prevalence and
      both the general and IBD-specific risk factors for the development of
      osteoporosis and of fracture in persons with IBD. We will also examine the role
      of the inflammatory process in IBD promoting excessive bone mineral loss, as well
      as the role that low body mass, corticosteroid use, diet, and nutrient
      malabsorption play in contributing to bone disease. Last, we will discuss our
      recommendation for: screening for osteoporosis in IBD patients, the use of
      preventative strategies, and therapeutic interventions for treating osteoporosis
      in persons with IBD. 

PMID- 24139750
TI  - Symptomatic heterotopic bone formation after rhBMP-2 utilization in lateral
      lumbar interbody fusion.

PMID- 24139751
TI  - Predicting excessive hemorrhage in adolescent idiopathic scoliosis patients
      undergoing posterior spinal instrumentation and fusion.
AB  - BACKGROUND CONTEXT: Blood loss in patients with adolescent idiopathic scoliosis
      (AIS) who are undergoing posterior spinal instrumentation and fusion (PSIF)
      varies greatly. The reason for this wide range is not clear. There are reports of
      unexpected massive hemorrhage during these surgeries. Many studies reflect
      authors' preferences for describing blood loss in terms of levels fused, weight,
      or percent blood volume. PURPOSE: We sought to define excessive blood loss
      clinically, determine its incidence in our study population, and identify
      associated variables. Results are intended to inform perioperative preparation
      for these cases. Results may be used to inform prospective study designs. STUDY
      DESIGN: This was a retrospective uncontrolled case series. PATIENT SAMPLE: A
      total of 311 consecutive AIS PSIF cases during the years 2005-2010 performed at
      Children's Hospital Colorado were studied. OUTCOME MEASURES: We measured
      estimated blood loss (EBL) and its association with multiple patient, surgical,
      and anesthetic variables. METHODS: Thirty-one variables potentially related to
      blood loss were collected retrospectively from electronic medical records for
      analysis. When no cases of clearly excessive blood loss were identified on the
      basis of visual examination of EBL distribution, we chose to use the top 10% of
      blood loss cases as an arbitrary determinant of excessive blood loss. Three cut
      off strategies captured the top 10% of EBL cases with little variation in who was
      selected: 1) >1,700 mL of EBL, 2) >50% EBL/estimated blood volume, and 3) >150
      mL/level fused EBL. Variables were compared with the chi(2) test, Fisher exact,
      or t-tests, when appropriate. A generalized linear mixed logistic model was used
      to determine the probability of excessive blood loss based on the number of
      levels fused. RESULTS: The average EBL was 89.17 mL/level fused (range, 45-133
      mL). EBL fit a progressively wider distribution as surgical complexity (number of
      levels fused) increased. Number of levels fused (p<.0001), operative time
      (p=.0139), number of screws (p<.0001), and maximal preoperative Cobb angle
      (p=.0491) were significantly associated with excessive blood loss. The variable
      that was most strongly associated with excessive blood loss was the number of
      levels fused, with >=12 levels having a probability of >10% of excessive
      hemorrhage. CONCLUSION: Excessive blood loss may be an arbitrary number until
      future research suggests otherwise. We show that the probability of exceeding one
      of our arbitrary definitions is approximately 10% when 12 or more levels are
      fused. If a 10% incidence of excessive blood loss is determined to be clinically
      relevant, teams might wish to pursue hematologic consultation and maximal blood
      conservation strategy when 12 or more levels are planned for fusion.

PMID- 24139752
TI  - Bipolar radiofrequency ablation of spinal tumors: predictability, safety and
      outcome.
AB  - BACKGROUND: Bone metastases are often the cause of tumor-associated pain and
      reduction of quality of life. For patients that cannot be treated by surgery, a
      local minimally invasive therapy such as radiofrequency ablation can be a useful
      option. In cases in which tumorous masses are adjacent to vulnerable structures,
      the monopolar radiofrequency can cause severe neuronal damage because of the
      unpredictability of current flow. PURPOSE: The aim of this study is to show that
      the bipolar radiofrequency ablation provides an opportunity to safely treat such
      spinal lesions because of precise predictability of the emerging ablation zone.
      STUDY DESIGN: Prospective cohort study of 36 patients undergoing treatment at a
      single institution. PATIENT SAMPLE: Thirty-six patients in advanced tumor stage
      with primary or secondary tumor involvement of spine undergoing radiofrequency
      ablation. OUTCOME MEASURES: Prediction of emerging ablation zone. Clinical
      outcome of treated patients. METHODS: X-ray-controlled treatment of 39 lesions by
      bipolar radiofrequency ablation. Magnetic resonance imaging was performed pre-
      and postinterventionally. Patients were observed clinically during their
      postinterventional stay. RESULTS: The extent of the ablation zones was
      predictable to the millimeter because it did not cross the peri-interventional
      planned dorsal and ventral boundaries in any case. No complications were
      observed. CONCLUSIONS: Ablation of tumorous masses adjacent to vulnerable
      structures is feasible and predictable by using the bipolar radiofrequency
      ablation. Damage of neuronal structures can be avoided through precise prediction
      of the ablation area.

PMID- 24139754
TI  - The role of ultrasound-guided triamcinolone injection in the treatment of de
      Quervain's disease: treatment and a diagnostic tool?
AB  - The purpose of this study was to describe the technique and usefulness of
      ultrasound-guided intrasheath injection of triamcinolone in the treatment of de
      Quervain's disease (dQD). Our study was retrospective in design. Seventy-one
      wrists of 62 patients who were treated with an ultrasound-guided triamcinolone
      injection for dQD were included. A literature search was performed to compare our
      results. In the literature we found supportive evidence that accurate injection
      of triamcinolone in the first dorsal compartment of the wrist is important for a
      good outcome. In this retrospective study we found that treatment with ultrasound
      guided injections of triamcinolone is both safe and effective. After two
      injections, 91% of the patients had good long-term results, which is a higher
      cure rate than found in most other studies. Furthermore, we found that
      Finkelstein's test can give a false positive result. Therefore, ultrasound should
      not only be considered to improve the treatment outcome, but can also be useful
      as a diagnostic tool in the management of de Quervain's disease. 

PMID- 24139753
TI  - Innervation of pathologies in the lumbar vertebral end plate and intervertebral
      disc.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) has limited diagnostic value
      for chronic low back pain because of the unclear relationship between any
      anatomic abnormalities on MRI and pain reported by the patient. Assessing the
      innervation of end plate and disc pathologies-and determining the relationship
      between these pathologies and any abnormalities seen on MRI-could clarify the
      sources of back pain and help identify abnormalities with enhanced diagnostic
      value. PURPOSE: To quantify innervation in the vertebral end plate and
      intervertebral disc and to relate variation in innervation to the presence of
      pathologic features observed by histology and conventional MRI. STUDY
      DESIGN/SETTING: A cross-sectional histology and imaging study of vertebral end
      plates and intervertebral discs harvested from human cadaver spines. METHODS: We
      collected 92 end plates and 46 intervertebral discs from seven cadaver spines
      (ages 51-67 years). Before dissection, the spines were scanned with MRI to grade
      for Modic changes and high-intensity zones (HIZ). Standard immunohistochemical
      techniques were used to localize the general nerve marker protein gene product
      9.5. We quantified innervation in the following pathologies: fibrovascular end
      plate marrow, fatty end-plate marrow, end-plate defects, and annular tears.
      RESULTS: Nerves were present in the majority of end plates with fibrovascular
      marrow, fatty marrow, and defects. Nerve density was significantly higher in
      fibrovascular end-plate marrow than in normal end-plate marrow (p<.001). Of the
      end plates with fibrovascular and fatty marrow, less than 40% were Modic on MRI.
      Innervated marrow pathologies collocated with more than 75% of the end plate
      defects; hence, innervation was significantly higher in end plate defects than in
      normal end plates (p<.0001). In the disc, nerves were observed in only 35% of the
      annular tears; in particular, innervation in radial tears tended to be higher
      than in normal discs (p=.07). Of the discs with radial tears, less than 13% had
      HIZ on T2 MRI. Innervation was significantly less in radial tears than in
      fibrovascular end-plate marrow (p=.05) and end-plate defects (p=.02).
      CONCLUSIONS: These findings indicate that vertebral end-plate pathologies are
      more innervated than intervertebral disc pathologies and that many innervated end
      plate pathologies are not detectable on MRI. Taken together, these findings
      suggest that improved visualization of end-plate pathologies could enhance the
      diagnostic value of MRI for chronic low back pain.

PMID- 24139755
TI  - Acid neutralizing, mechanical and physical properties of pit and fissure sealants
      containing melt-derived 45S5 bioactive glass.
AB  - OBJECTIVES: The aim of this study was to examine the effects of 45S5 bioactive
      glass (BAG) on the acid neutralizing, mechanical and physical properties of pit
      and fissure sealants. METHODS: 45S5BAG (<25 MUm) was mixed with the silanized
      glass (180 +/- 30 nm) and added into a resin matrix [Bis-GMA/TEGDMA 50/50 (wt%)
      containing 1% of DMAEMA/CQ 2:1 (wt%)] with varying filler proportions; 0%
      45S5BAG+50% glass (BAG0); 12.5% 45S5BAG+37.5% glass (BAG12.5); 25% 45S5BAG+25%
      glass (BAG25); 37.5% 45S5BAG+12.5% glass (BAG37.5); and 50% 45S5BAG+0% glass
      (BAG50). To evaluate the acid neutralizing properties, specimens were immersed in
      lactic acid solution (pH 4.0). Then, the change in pH and the time required to
      raise the pH from 4.0 to 5.5 were measured. In addition, flexural strength, water
      sorption and solubility were analyzed. RESULTS: The acid neutralizing properties
      of each group exhibited increasing pH values as more 45S5BAG was added, and the
      time required to raise the pH from 4.0 to 5.5 became shorter as the proportion of
      45S5BAG increased (P<0.05). Additionally, the flexural strength decreased
      according to the increasing proportions of 45S5BAG added (P<0.05). Water sorption
      showed an increasing trend with increasing proportions of 45S5 BAG added
      (P<0.05). However, the solubility results were similar among the groups (P>0.05),
      except for BAG50. SIGNIFICANCE: The novel pit and fissure sealants neutralized
      the acid solution (pH 4.0) and exhibited appropriate mechanical and physical
      properties. Therefore, these compounds are suitable candidates for caries
      inhibiting dental materials.

PMID- 24139756
TI  - Edge chipping and flexural resistance of monolithic ceramics.
AB  - OBJECTIVE: Test the hypothesis that monolithic ceramics can be developed with
      combined esthetics and superior fracture resistance to circumvent processing and
      performance drawbacks of traditional all-ceramic crowns and fixed-dental
      prostheses consisting of a hard and strong core with an esthetic porcelain
      veneer. Specifically, to demonstrate that monolithic prostheses can be produced
      with a much reduced susceptibility to fracture. METHODS: Protocols were applied
      for quantifying resistance to chipping as well as resistance to flexural failure
      in two classes of dental ceramic, microstructurally-modified zirconias and
      lithium disilicate glass-ceramics. A sharp indenter was used to induce chips near
      the edges of flat-layer specimens, and the results compared with predictions from
      a critical load equation. The critical loads required to produce cementation
      surface failure in monolithic specimens bonded to dentin were computed from
      established flexural strength relations and the predictions validated with
      experimental data. RESULTS: Monolithic zirconias have superior chipping and
      flexural fracture resistance relative to their veneered counterparts. While they
      have superior esthetics, glass-ceramics exhibit lower strength but higher chip
      fracture resistance relative to porcelain-veneered zirconias. SIGNIFICANCE: The
      study suggests a promising future for new and improved monolithic ceramic
      restorations, with combined durability and acceptable esthetics.

PMID- 24139757
TI  - The transcriptional and functional properties of mouse epiblast stem cells
      resemble the anterior primitive streak.
AB  - Mouse epiblast stem cells (EpiSCs) can be derived from a wide range of
      developmental stages. To characterize and compare EpiSCs with different origins,
      we derived a series of EpiSC lines from pregastrula stage to late-bud-stage mouse
      embryos. We found that the transcriptomes of these cells are hierarchically
      distinct from those of the embryonic stem cells, induced pluripotent stem cells
      (iPSCs), and epiblast/ectoderm. The EpiSCs display globally similar gene
      expression profiles irrespective of the original developmental stage of the
      source tissue. They are developmentally similar to the ectoderm of the late
      gastrula-stage embryo and behave like anterior primitive streak cells when
      differentiated in vitro and in vivo. The EpiSC lines that we derived can also be
      categorized based on a correlation between gene expression signature and
      predisposition to differentiate into particular germ-layer derivatives. Our
      findings therefore highlight distinct identifying characteristics of EpiSCs and
      provide a foundation for further examination of EpiSC properties and potential.

PMID- 24139758
TI  - Transplantation of expanded fetal intestinal progenitors contributes to colon
      regeneration after injury.
AB  - Regeneration and homeostasis in the adult intestinal epithelium is driven by
      proliferative resident stem cells, whose functional properties during organismal
      development are largely unknown. Here, we show that human and mouse fetal
      intestine contains proliferative, immature progenitors, which can be expanded in
      vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can
      be established during intestinal differentiation of human induced pluripotent
      stem cells. Established cultures of mouse fetal intestinal progenitors express
      lower levels of Lgr5 than mature progenitors and propagate in the presence of the
      Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal
      organoids by exposure to Wnt3a. Following transplantation in a colonic injury
      model, FEnS contribute to regeneration of colonic epithelium by forming
      epithelial crypt-like structures expressing region-specific differentiation
      markers. This work provides insight into mechanisms underlying development of the
      mammalian intestine and points to future opportunities for patient-specific
      regeneration of the digestive tract.

PMID- 24139759
TI  - PTP1B is an effector of activin signaling and regulates neural specification of
      embryonic stem cells.
AB  - During embryogenesis, the Activin/Nodal pathway promotes the mesendodermal
      lineage and inhibits neural fate. The molecular mechanisms underlying this role
      of the Activin/Nodal pathway are not clear. In this study, we report a role for
      protein tyrosine phosphatase 1B (PTP1B) in Activin-mediated early fate decisions
      during ESC differentiation and show that PTP1B acts as an effector of the Activin
      pathway to specify mesendodermal or neural fate. We found that the Activin/ALK4
      pathway directly recruits PTP1B and stimulates its release from the endoplasmic
      reticulum through ALK4-mediated cleavage. Subsequently, PTP1B suppresses p-ERK1/2
      signaling to inhibit neural specification and promote mesendodermal commitment.
      These findings suggest that a noncanonical Activin signaling pathway functions in
      lineage specification of mouse and human embryonic stem cells. 

PMID- 24139760
TI  - Evaluation of three bovine Y specific microsatellite loci as an alternative
      biomarkers for semen quality traits in crossbred bull.
AB  - Although some of the studies earlier reported that bovine semen parameters are
      associated with some candidate markers genes, but scanty of reports available
      regarding the effect of allelic variation in Y specific microsatellite markers on
      semen quality parameters in bulls. In the present study we have targeted three Y
      specific microsatellite markers (INRA126, INRA 189 and BM861) for their
      association ship analysis with some semen quality parameters among Frieswal (HF *
      Sahiwal) crossbred bulls of Indian origin. The polymorphic loci of INRA 126,
      bulls with 182 and 184 alleles had significantly (P<0.01) higher semen volume as
      compared to 186 allele, however, 186 allele showed significantly (P<0.01) higher
      concentration per ml of semen compared to 182 and 184. Interestingly our study
      also revealed that number of sperm/ejaculate is also significantly (P<0.05)
      higher in 184 allele compared to 182 and 186. Similarly, association analysis of
      INRA 189 major three alleles also revealed a significant difference in semen
      volume and concentration. Allele 89 and 96 having significantly (P<0.01) higher
      volume compared to 86, whereas allele 86 having significantly (P<0.01) higher
      concentration per volume of semen than 89 and 96. Again after association of two
      major alleles (160 and 164) of BM861 loci with semen parameters revealed no
      significant difference with any of the semen quality parameters chosen here.
      Therefore the present study may be for the first time revealed that the Y
      chromosomal microsatellite alleles are important male reproductive biomarkers for
      improving semen quality traits in bulls.

PMID- 24139761
TI  - Effects of Improvac and Bopriva on the testicular function of boars ten weeks
      after immunization.
AB  - This study investigated the effects of Improvac and Bopriva, two anti-GnRF
      immunization products, on testicular function in boars. We predicted that both
      products would diminish testicular function; however, we specifically tested the
      hypothesis that the duration of efficacy for Bopriva would be longer than that of
      Improvac. Animals were immunized with either Improvac or Bopriva and then
      observed ten weeks after the second injection. Serum GnRF antibody titers rose
      after the second injection and peaked approximately two weeks later. At the same
      time testosterone concentrations decreased to undetectable levels and remained
      below assay detection for at least six weeks. At approximately eight weeks,
      testosterone began to increase in animals treated with Improvac though levels
      remained decreased in Bopriva treated animals throughout the ten weeks. Daily
      sperm production at 10 weeks was significantly reduced in both treatment groups;
      however, the reduction was greater in Bopriva treated boars. Examination of
      testes of both treatments revealed incomplete spermatogenesis with impaired
      spermatid production and reduced seminiferous tubule diameter. These findings
      were universal in Bopriva treated animals, but Improvac treated animals exhibited
      morphologies intermediate between Bopriva treated animals and control boars.
      Overall testicular function in Bopriva boars remained suppressed ten weeks post
      immunization while Improvac boars appeared to be recovering. 

PMID- 24139762
TI  - Biochemical and steroid concentrations in follicular fluid and blood plasma in
      different follicular waves of the estrous cycle from normal and superovulated
      beef cows.
AB  - The objectives of the current study were to (i) define the changes in size and
      number of follicles populations, (ii) determine the follicular fluid (FF)
      biochemical and steroid concentrations collected from different-sized follicles
      (5-9 and >= 10 mm) and (iii) compare between biochemical and hormonal
      concentrations of FF with those in blood plasma in relation to the first two
      follicular waves of the estrous cycle (days 4 and 13) from normal and cows primed
      for superovulation. After estrus, cows (n=20) were assigned randomly to each of
      four treatment groups. Group 1: ovariectomy on day 4 (day 0 = ovulation). Group
      2: FSH treatment and ovariectomy on day 4. Group 3: dominant follicle ablation
      (DFA) on day 8 and ovariectomy on day 13. Group 4: DFA on day 8, FSH treatment
      and ovariectomy on day 13. Blood samples were collected and FF was aspirated and
      pooled per follicle class within cow to determine glucose, urea, triglycerides,
      cholesterol, total protein, albumin, lactate dehydrogenase, alkaline phosphatase,
      gamma-glutamyl transpeptidase, aspartate aminotransferase, creatin phosphokinase,
      estradiol-17beta and progesterone concentrations. Follicular class*follicular
      wave interaction was detected for albumin and lactate dehydrogenase. Results
      showed that FF concentrations of cholesterol increased from medium to large
      follicles and decreased for urea and aspartate aminotransferase. Tryglycerides
      and total protein were greater in the second than in the first follicular wave.
      FSH treatment decreased FF alkaline phosphatase, E2 and P4 concentrations.
      Quantitative differences between these fluids are discussed with respect to
      follicular development.

PMID- 24139763
TI  - Targeting hepatocyte growth factor receptor (Met) positive tumor cells using
      internalizing nanobody-decorated albumin nanoparticles.
AB  - The hepatocyte growth factor receptor (HGFR, c-Met or Met) is a receptor tyrosine
      kinase that is involved in embryogenesis, tissue regeneration and wound healing.
      Abnormal activation of this proto-oncogene product is implicated in the
      development, progression and metastasis of many cancers. Current therapies
      directed against Met, such as ligand- or, dimerization-blocking antibodies or
      kinase inhibitors, reduce tumor growth but hardly eradicate the tumor. In order
      to improve anti-Met therapy, we have designed a drug delivery system consisting
      of crosslinked albumin nanoparticles decorated with newly selected anti-Met
      nanobodies (anti-Met-NANAPs). The anti-Met NANAPs bound specifically to and were
      specifically taken up by Met-expressing cells and transported to lysosomes for
      degradation. Treatment of tumor cells with anti-Met NANAPs also resulted in
      downregulation of the total Met protein. This study shows that anti-Met NANAPs
      offer a potential system for lysosomal delivery of drugs into Met-positive tumor
      cells. 

PMID- 24139764
TI  - A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle.
AB  - A cancer-recognizable MRI contrast agents (CR-CAs) has been developed using pH
      responsive polymeric micelles. The CR-CAs with pH sensitivity were self-assembled
      based on well-defined amphiphilic block copolymers, consisting of methoxy
      poly(ethylene glycol)-b-poly(L-histidine) (PEG-p(L-His)) and methoxy
      poly(ethylene glycol)-b-poly(L-lactic acid)-diethylenetriaminopentaacetic acid
      dianhydride-gadolinium chelate (PEG-p(L-LA)-DTPA-Gd). The CR-CAs have a spherical
      shape with a uniform size of ~40 nm at physiological pH (pH 7.4). However, in
      acidic tumoral environment (pH 6.5), the CR-CAs were destabilized due to the
      protonation of the imidazole groups of p(L-His) blocks, causing them to break
      apart into positively charged water-soluble polymers. As a result, the CR-CAs
      exhibit highly effective T1 MR contrast enhancement in the tumor region, which
      enabled the detection of small tumors of ~3 mm(3 )in vivo at 1.5 T within a few
      minutes.

PMID- 24139765
TI  - Commitment contracts and team incentives: a randomized controlled trial for
      smoking cessation in Thailand.
AB  - BACKGROUND: Treatment for tobacco dependence is not available in many low
      resource settings, especially in developing countries. PURPOSE: To test the
      impact of a novel mix of monetary and social incentives on smoking abstinence in
      rural communities of Thailand. DESIGN: An RCT of commitment contracts and team
      incentives for rural smokers to quit smoking. Smokers were not blinded to
      treatment status, although the assessor of the biochemical urine test was.
      SETTING/PARTICIPANTS: All adult smokers living in the study area were eligible to
      participate; 215 adult smokers from 42 villages in Nakhon Nayok province,
      Thailand, participated. Fourteen smokers who lacked teammates were dropped.
      INTERVENTION: A total of 201 smokers were assigned to a two-person team, and then
      randomly assigned by team (in a 2:1 ratio) with computer-generated random numbers
      to receive smoking-cessation counseling (control group) or counseling plus offer
      of a commitment contract, team incentives, and text message reminders for smoking
      cessation at 3 months (intervention group). MAIN OUTCOME MEASURES: The primary
      outcome was biochemically verified 7-day abstinence at 6 months, assessed on an
      intention-to-treat basis. Secondary outcomes include study participation,
      biochemically verified abstinence at 3 months, self-reported abstinence at 14
      months, and the incremental cost per quitter of the intervention, nicotine gum,
      and varenicline in Thailand. Data were collected in 2010-2011 and analyzed in
      2012. RESULTS: The trial enrolled 215 (10.5%) of 2055 smokers. The abstinence
      rate was 46.2% (61/132) in the intervention group and 14.5% (10/69) in the
      control group (adjusted OR 7.5 [3.0-18.6]) at 3 months; 44.3% (58/131) and 18.8%
      (13/69) at the primary end point of 6 months (adjusted OR 4.2 [1.8-9.7]); and
      42.0% (55/131) and 24.6% (17/69) at 14 months (adjusted OR 2.2 [1.0-4.8]). The
      purchasing power parity-adjusted incremental cost per quitter from the
      intervention is $281 (95% CI=$187, $562), less than for nicotine gum ($1780, 95%
      CI=$1414, $2401) or varenicline ($2073, 95% CI=$1357, $4388) in Thailand.
      CONCLUSIONS: The intervention enhanced abstinence by 91%-136% at 6 months,
      relative to the control group, although self-reports at 14 months suggest
      tapering of the treatment effect. The intervention may offer a viable, cost
      effective alternative to current smoking-cessation approaches in low-resource
      settings. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov
      NCT01311115.

PMID- 24139766
TI  - Crowdsourced peer- versus expert-written smoking-cessation messages.
AB  - BACKGROUND: Tailored, web-assisted interventions can reach many smokers. Content
      from other smokers (peers) through crowdsourcing could enhance relevance.
      PURPOSE: To evaluate whether peers can generate tailored messages encouraging
      other smokers to use a web-assisted tobacco intervention (Decide2Quit.org).
      METHODS: Phase 1: In 2009, smokers wrote messages in response to scenarios for
      peer advice. These smoker-to-smoker (S2S) messages were coded to identify themes.
      Phase 2: resulting S2S messages, and comparison expert messages, were then e
      mailed to newly registered smokers. In 2012, subsequent Decide2Quit.org visits
      following S2S or expert-written e-mails were compared. RESULTS: Phase 1: a total
      of 39 smokers produced 2886 messages (message themes: attitudes and expectations,
      improvements in quality of life, seeking help, and behavioral strategies). For
      not-ready-to-quit scenarios, S2S messages focused more on expectations around a
      quit attempt and how quitting would change an individual's quality of life. In
      contrast, for ready-to-quit scenarios, S2S messages focused on behavioral
      strategies for quitting. Phase 2: In multivariable analysis, S2S messages were
      more likely to generate a return visit (OR=2.03, 95% CI=1.74, 2.35), compared to
      expert messages. A significant effect modification of this association was found,
      by time-from-registration and message codes (both interaction terms p<0.01). In
      stratified analyses, S2S codes that were related more to "social" and "real-life"
      aspects of smoking were driving the main association of S2S and increased return
      visits. CONCLUSIONS: S2S peer messages that increased longitudinal engagement in
      a web-assisted tobacco intervention were successfully collected and delivered.
      S2S messages expanded beyond the biomedical model to enhance relevance of
      messages. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov
      NCT00797628 (web-delivered provider intervention for tobacco control [QUIT
      PRIMO]) and NCT01108432 (DPBRN Hygienists Internet Quality Improvement in Tobacco
      Cessation [HiQuit]).

PMID- 24139767
TI  - Solid fat and added sugar intake among U.S. children: The role of stores,
      schools, and fast food, 1994-2010.
AB  - BACKGROUND: Little is known about the role of location in U.S. children's excess
      intake of energy from solid fat and added sugar, collectively referred to as
      SoFAS. PURPOSE: The goal of this study was to compare the SoFAS content of foods
      consumed by children from stores, schools, and fast-food restaurants and to
      determine whether trends from 1994 to 2010 differ across these locations.
      METHODS: Children aged 2-18 years (N=22,103) from five nationally representative
      surveys of dietary intake from 1994 to 2010 were studied. SoFAS content was
      compared across locations for total intake and key foods. Regression models were
      used to test and compare linear trends across locations. Data were analyzed in
      2012. RESULTS: The mean percentage of total energy intake consumed from each
      location that was provided by SoFAS remained above recommendations, despite
      significant improvements between 1994 and 2010 at stores (1994, 38.3%; 2004,
      33.2%); schools (1994, 38.7%; 2004, 31.2%); and fast-food restaurants (1994,
      34.6%; 2004, 34.6%). For each key food, SoFAS content decreased significantly at
      stores and schools, yet progress at schools was comparatively slower. Milk was
      higher in SoFAS at schools compared to stores because of shifts toward flavored
      milk at schools. Schools provided french fries that were higher in solid fat than
      store-bought versions and pizza that was not significantly different in SoFAS
      content than fast-food pizza. However, schools made significantly greater
      progress for sugar-sweetened beverages, as lower-sugar beverages replaced regular
      sodas. Key fast foods showed little improvement. CONCLUSIONS: These findings can
      inform future strategies targeted to the specific locations and foods where
      continued progress is needed to reduce children's SoFAS consumption.

PMID- 24139768
TI  - Receptivity to television fast-food restaurant marketing and obesity among U.S.
      youth.
AB  - BACKGROUND: Advertisement of fast food on TV may contribute to youth obesity.
      PURPOSE: The goal of the study was to use cued recall to determine whether TV
      fast-food advertising is associated with youth obesity. METHODS: A national
      sample of 2541 U.S. youth, aged 15-23 years, were surveyed in 2010-2011; data
      were analyzed in 2012. Respondents viewed a random subset of 20 advertisement
      frames (with brand names removed) selected from national TV fast-food restaurant
      advertisements (n=535) aired in the previous year. Respondents were asked if they
      had seen the advertisement, if they liked it, and if they could name the brand. A
      TV fast-food advertising receptivity score (a measure of exposure and response)
      was assigned; a 1-point increase was equivalent to affirmative responses to all
      three queries for two separate advertisements. Adjusted odds of obesity (based on
      self-reported height and weight), given higher TV fast-food advertising
      receptivity, are reported. RESULTS: The prevalence of overweight and obesity,
      weighted to the U.S. population, was 20% and 16%, respectively. Obesity, sugar
      sweetened beverage consumption, fast-food restaurant visit frequency, weekday TV
      time, and TV alcohol advertising receptivity were associated with higher TV fast
      food advertising receptivity (median=3.3 [interquartile range: 2.2-4.2]). Only
      household income, TV time, and TV fast-food advertising receptivity retained
      multivariate associations with obesity. For every 1-point increase in TV fast
      food advertising receptivity score, the odds of obesity increased by 19%
      (OR=1.19, 95% CI=1.01, 1.40). There was no association between receptivity to
      televised alcohol advertisements or fast-food restaurant visit frequency and
      obesity. CONCLUSIONS: Using a cued-recall assessment, TV fast-food advertising
      receptivity was found to be associated with youth obesity.

PMID- 24139769
TI  - A novel food pantry program: food security, self-sufficiency, and diet-quality
      outcomes.
AB  - BACKGROUND: The number of food pantries in the U.S. has grown dramatically over 3
      decades, yet food insecurity remains a persistent public health problem. PURPOSE:
      The goal of the study was to examine the impact of a food pantry intervention
      called Freshplace, designed to promote food security. DESIGN: Randomized parallel
      group study with equal randomization. SETTING/PARTICIPANTS: Data were collected
      from June 2010 to June 2012; a total of 228 adults were recruited over 1 year
      from traditional food pantries and randomized to the Freshplace intervention
      (n=113) or control group (n=115), with quarterly follow-ups for 12 months.
      INTERVENTION: The Freshplace intervention included a client-choice pantry,
      monthly meetings with a project manager to receive motivational interviewing, and
      targeted referrals to community services. Control group participants went to
      traditional food pantries where they received bags of food. MAIN OUTCOME
      MEASURES: Data analyses were conducted from July 2012 to January 2013. Outcomes
      were food security, self-sufficiency, and fruit and vegetable consumption.
      Multivariate regression models were used to predict the three outcomes,
      controlling for gender, age, household size, income, and presence of children in
      the household. RESULTS: At baseline, half of the sample experienced very low food
      security. Over 1 year, Freshplace members were less than half as likely to
      experience very low food security, increased self-sufficiency by 4.1 points, and
      increased fruits and vegetables by one serving per day compared to the control
      group, all outcomes p<0.01. CONCLUSIONS: Freshplace may serve as a model for
      other food pantries to promote food security rather than short-term assistance by
      addressing the underlying causes of poverty.

PMID- 24139770
TI  - Evidence-based strategies in weight-loss mobile apps.
AB  - BACKGROUND: Physicians have limited time for weight-loss counseling, and there is
      a lack of resources to which they can refer patients for assistance with weight
      loss. Weight-loss mobile applications (apps) have the potential to be a helpful
      tool, but the extent to which they include the behavioral strategies included in
      evidence-based interventions is unknown. PURPOSE: The primary aims of the study
      were to determine the degree to which commercial weight-loss mobile apps include
      the behavioral strategies included in evidence-based weight-loss interventions,
      and to identify features that enhance behavioral strategies via technology.
      METHODS: Thirty weight-loss mobile apps, available on iPhone and/or Android
      platforms, were coded for whether they included any of 20 behavioral strategies
      derived from an evidence-based weight-loss program (i.e., Diabetes Prevention
      Program). Data on available apps were collected in January 2012; data were
      analyzed in June 2012. RESULTS: The apps included on average 18.83% (SD=13.24;
      range=0%-65%) of the 20 strategies. Seven of the strategies were not found in any
      app. The most common technology-enhanced features were barcode scanners (56.7%)
      and a social network (46.7%). CONCLUSIONS: Weight-loss mobile apps typically
      included only a minority of the behavioral strategies found in evidence-based
      weight-loss interventions. Behavioral strategies that help improve motivation,
      reduce stress, and assist with problem solving were missing across apps.
      Inclusion of additional strategies could make apps more helpful to users who have
      motivational challenges.

PMID- 24139771
TI  - Mobile applications for weight management: theory-based content analysis.
AB  - BACKGROUND: The use of smartphone applications (apps) to assist with weight
      management is increasingly prevalent, but the quality of these apps is not well
      characterized. PURPOSE: The goal of the study was to evaluate diet/nutrition and
      anthropometric tracking apps based on incorporation of features consistent with
      theories of behavior change. METHODS: A comparative, descriptive assessment was
      conducted of the top-rated free apps in the Health and Fitness category available
      in the iTunes App Store. Health and Fitness apps (N=200) were evaluated using
      predetermined inclusion/exclusion criteria and categorized based on commonality
      in functionality, features, and developer description. Four researchers then
      evaluated the two most popular apps in each category using two instruments: one
      based on traditional behavioral theory (score range: 0-100) and the other on the
      Fogg Behavioral Model (score range: 0-6). Data collection and analysis occurred
      in November 2012. RESULTS: Eligible apps (n=23) were divided into five
      categories: (1) diet tracking; (2) healthy cooking; (3) weight/anthropometric
      tracking; (4) grocery decision making; and (5) restaurant decision making. The
      mean behavioral theory score was 8.1 (SD=4.2); the mean persuasive technology
      score was 1.9 (SD=1.7). The top-rated app on both scales was Lose It! by Fitnow
      Inc. CONCLUSIONS: All apps received low overall scores for inclusion of
      behavioral theory-based strategies.

PMID- 24139772
TI  - Physical activity in parks: A randomized controlled trial using community
      engagement.
AB  - BACKGROUND: Physical inactivity is an important health risk factor that could be
      addressed at the community level. PURPOSE: The goal of the study was to determine
      whether using a community-based participatory approach with park directors and
      park advisory boards (PABs) could increase physical activity in local parks.
      Whether involving PABs would be more effective than working with park directors
      alone was also tested. DESIGN: An RCT intervention from October 2007 to April
      2012 was used, with partial blinding of observers to the condition. All data were
      analyzed in 2012. SETTING/PARTICIPANTS: Of 183 eligible parks in the City of Los
      Angeles, 50 neighborhood park/recreation centers serving diverse populations
      participated. Parks were randomized to three study arms: (1) park-director
      intervention (PD-only); (2) PAB intervention (PAB/PD); and (3) a control arm.
      Physical activity in each park was systematically observed, and park users and
      residents living within 1 mile of the park were interviewed. INTERVENTION(S): The
      intervention included assessing park use, obtaining feedback from park users and
      community residents, training on outreach and marketing, and giving each
      intervention park $4000 to increase park-based physical activity. The PAB/PD arm
      required participation and concurrence on all purchases by the PAB. MAIN OUTCOME
      MEASURE(S): Change in the number of park users and change in the level of park
      based physical activity, expressed as MET-hours. RESULTS: Relative to control
      parks where physical activity declined, in both the PD-only and PAB/PD parks,
      physical activity increased, generating an estimated average of 600 more
      visits/week/park, and 1830 more MET-hours of physical activity/week/park. Both
      residents and park users in the intervention arms in the intervention arms
      reported increased frequency of exercise. No differences were noted between the
      PD-only and PAB/PD study arms. CONCLUSIONS: Providing park directors and PABs
      with training on outreach and marketing, feedback on park users, and modest funds
      increased the amount of physical activity observed in parks.

PMID- 24139773
TI  - The Seamos Saludables study: A randomized controlled physical activity trial of
      Latinas.
AB  - BACKGROUND: Latinas in the U.S. are less physically active than non-Latino white
      women and also report higher levels of diabetes, obesity, and other conditions
      related to inactivity. Interventions are needed to address disparities in this
      high-risk group. PURPOSE: To evaluate the efficacy of a culturally adapted,
      Spanish-language, individually tailored, computer expert system-driven physical
      activity print-based intervention for adult Latinas. DESIGN: RCT.
      SETTING/PARTICIPANTS: Participants were 266 inactive adult Latinas who
      participated between 2009 and 2012. INTERVENTION: Participants were randomized to
      one of two treatment arms: a 6-month tailored physical activity intervention
      condition or wellness contact control. For both conditions, print materials were
      delivered by mail. MAIN OUTCOME MEASURES: The main outcome measure was change in
      weekly moderate-to-vigorous physical activity (MVPA) measured by the 7-Day
      Physical Activity Recall interview, which was administered at baseline and post
      intervention (6 months). Participants also wore accelerometers for a week at
      baseline and follow-up. Analyses were conducted in 2013. RESULTS: Increases in
      minutes/week of MVPA measured by the 7-Day PAR were significantly greater in the
      intervention group compared to the control group (mean difference=41.36, SE=7.93,
      p<0.01). This difference was corroborated by accelerometer readings (rho=0.44,
      p<0.01). Further, results indicate that intervention participants had greater
      increases in self-efficacy, cognitive processes, and behavioral processes at 3
      months compared to control paricipants (p's<0.05). CONCLUSIONS: The tailored
      Spanish-language intervention was effective in increasing MVPA among
      predominantly low-income, less-acculturated Latinas. Such print-based
      interventions are poised for widespread dissemination, and thus may help address
      health disparities.

PMID- 24139774
TI  - Urban food environments and residents' shopping behaviors.
AB  - BACKGROUND: Food environments may promote or undermine healthy behaviors, but
      questions remain regarding how individuals interact with their local food
      environments. PURPOSE: This study incorporated an urban food environment audit as
      well as an examination of residents' food shopping behaviors within that context.
      METHODS: In 2010, the research team audited the variety and healthfulness of
      foods available in 373 Philadelphia stores, using the validated Nutrition
      Environment Measures Survey in Stores (NEMS-S); higher scores indicate more
      diverse and healthful food inventories. The team also surveyed urban residents
      (n=514) regarding their food shopping. Descriptive and multivariate analyses
      (conducted in 2012) assessed variation in retail food environments and in
      shoppers' store choices. RESULTS: Corner and convenience stores were common
      (78.6% of food retail outlets) and had the lowest mean NEMS-S scores of any store
      type. Most participants (94.5%) did their primary food shopping at higher-scoring
      chain supermarkets, and the majority of participants did not shop at the
      supermarket closest to home. Supermarket offerings varied, with significantly
      fewer healthful foods at supermarkets closest to the homes of disadvantaged
      residents. In multivariate analyses, participants were significantly more likely
      to shop at supermarkets closest to home if those supermarkets had higher NEMS-S
      scores. CONCLUSIONS: These data suggest that, when possible, shoppers chose
      supermarkets that offered more variety and more healthful foods. Findings from
      this study also reinforce concern regarding unhealthy immediate food environments
      for disadvantaged residents, who disproportionately relied on nearby stores with
      more limited food items. Interventions to improve nutrition and health should
      address not only food store proximity but also diversity of healthful foods
      available.

PMID- 24139775
TI  - Overstatement of results in the nutrition and obesity peer-reviewed literature.
AB  - BACKGROUND: Scientific authors who overreach in presenting results can
      potentially, without intending to, distort the state of knowledge and
      inappropriately influence clinicians, decision makers, the media, and the public.
      PURPOSE: The goal of the study was to determine the extent to which authors
      present overreaching statements in the obesity and nutrition literature, and
      whether journal, author, or study characteristics are associated with this
      practice. METHODS: A total of 937 papers on nutrition or obesity published in
      2001 and 2011 in leading specialty, medical, and public health journals were
      systematically studied to estimate the extent to which authors overstate the
      results of their study in the published abstract. Focus was placed on
      overreaching statements that may include (1) reporting an associative
      relationship as causal; (2) making policy recommendations based on observational
      data that show associations only (e.g., not cause and effect); and (3)
      generalizing to a population not represented by their sample. Data were compiled
      in 2012 and analyzed in 2013. RESULTS: Results indicate that 8.9% of studies have
      overreaching conclusions with a higher percentage in 2011 compared to 2001
      (OR=2.14, risk difference=+3.9%, p=0.020). Unfunded studies (OR=2.41, p=0.039)
      were more likely to have an overstatement of results of the type described here.
      In contrast, those with a greater number of coauthors were significantly less
      likely than those with four or fewer authors (the reference group) to have
      overstated results (seven or eight authors: OR=0.30, risk difference=-6.1%,
      p=0.008; >=9 authors: OR=0.41, risk difference= -4.0%, p=0.037). CONCLUSIONS:
      Overreaching in presenting results in studies focused on nutrition and obesity
      topics is common in articles published in leading journals. Testable strategies
      are proposed to reduce the prevalence of such instances in the literature.

PMID- 24139776
TI  - Predictors of the timing of vaccination uptake: The 2009 influenza pandemic
      (H1N1) in Montreal.
AB  - BACKGROUND: In response to the 2009 H1N1 influenza pandemic, Canada undertook the
      largest vaccination campaign in its history. The effort mobilized thousands of
      healthcare workers, cost many hundreds of millions of dollars, and vaccinated
      more than 40% of the population. Despite the large investment in mass vaccination
      internationally, little is known about the factors that drive the timing of
      vaccination uptake. PURPOSE: Data from 2009 were used to investigate three
      potential determinants of vaccination uptake in Montreal, Canada. METHODS:
      Poisson regression was used to analyze daily vaccination before and after a
      telephone intervention targeting households in 12 of the city's 29 health
      neighborhoods. The effect of an eligibility strategy based on risk groups, and of
      weather, on uptake was then estimated. Data were analyzed in 2013. RESULTS:
      Considerable variation in daily mass vaccination was observed, with the peak day
      (30,204 individuals) accounting for nearly five times the uptake of the slowest
      day (6298 individuals). No evidence was found that the telephone intervention led
      to a significant increase in vaccination. Daily vaccination was associated
      significantly with weather conditions, including mean temperature (relative risk
      [RR]=1.28, 95% CI=1.12, 1.46) and heavy precipitation (RR=0.63, 95% CI=0.45,
      0.89), even after accounting for changes to eligibility, which also were
      associated with increased vaccination. CONCLUSIONS: Considerable temporal
      variation in uptake can occur during mass vaccination efforts. Targeted
      interventions to increase vaccination should be evaluated further, as a large
      intervention had no observable effect. Mass vaccination campaigns should,
      however, attempt to optimize priority sequences and account for weather when
      estimating vaccine demand.

PMID- 24139777
TI  - Adverse pregnancy outcomes following motor vehicle crashes.
AB  - BACKGROUND: Motor vehicle crashes are a leading cause of serious trauma during
      pregnancy, but little is known about their relationships with pregnancy outcomes.
      PURPOSE: To estimate the association between motor vehicle crashes and adverse
      pregnancy outcomes. METHODS: A retrospective cohort study of 878,546 pregnant
      women, aged 16-46 years, who delivered a singleton infant in North Carolina from
      2001 to 2008. Pregnant drivers in crashes were identified by probabilistic
      linkage of vital records and crash reports. Poisson regression modeled the
      association among crashes, vehicle safety features, and adverse pregnancy
      outcomes. Analyses were conducted in 2012. RESULTS: In 2001-2008, 2.9% of
      pregnant North Carolina women were drivers in one or more crashes. After a single
      crash, compared to not being in a crash, pregnant drivers had slightly elevated
      rates of preterm birth (adjusted rate ratio [aRR]=1.23, 95% CI=1.19, 1.28);
      placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the
      membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent
      crash, pregnant drivers had more highly elevated rates of preterm birth
      (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14);
      placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95%
      CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving
      unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted
      pregnant drivers. CONCLUSIONS: Crashes while driving during pregnancy were
      associated with elevated rates of adverse pregnancy outcomes, and multiple
      crashes were associated with even higher rates of adverse pregnancy outcomes.
      Crashes were especially harmful if drivers were unbelted.

PMID- 24139778
TI  - Assessment of club patrons' alcohol and drug use: the use of biological markers.
AB  - BACKGROUND: Young adulthood (ages 18-25 years) represents a time when high-risk
      behaviors, including alcohol and drug use, peak. Electronic music dance events
      (EMDEs) featured at clubs provide an ecologic niche for these high-risk
      behaviors. PURPOSE: This paper examines the prevalence of alcohol and drug use
      among EMDE patrons. Examination of personal characteristics associated with exit
      levels of alcohol and drug use identifies important indicators of risk taking for
      prevention strategies. METHODS: Data were collected anonymously during 2010-2012
      from 2028 patrons as they entered and exited clubs in the San Francisco Bay area
      featuring EMDEs. Nearly half were aged <=25 years. Biological measures of drug
      and alcohol and self-reported personal characteristics were attained. Analyses
      were completed in 2012. RESULTS: At entrance, more than one fifth of patrons were
      positive for drug use and one fourth arrived either impaired (blood alcohol
      concentration [BAC]: 0.05%-0.079%) or intoxicated (BAC: >0.08%) by alcohol. At
      exit, one fourth tested positive for drugs, and nearly half were impaired or
      intoxicated by alcohol. Individual characteristics that were important for levels
      of risk included prior alcohol use behaviors, sexual identity, ethnic/racial
      identity, and transportation to the event. Gender did not differentiate for
      alcohol use but fewer women used drugs. CONCLUSIONS: Findings confirm the
      importance of targeting EMDEs for prevention efforts. EMDEs attract young working
      adults who are engaged in heavy alcohol and/or drug use. Targeting these social
      settings for delivering public health prevention strategies regarding alcohol and
      drug use and related harm is indicated by the findings.

PMID- 24139779
TI  - Colorectal Cancer Control Program grantees' use of evidence-based interventions.
AB  - BACKGROUND: Colorectal cancer (CRC) screening is recommended for adults aged 50
      75 years, yet screening rates are low, especially among the uninsured. The CDC
      initiated the Colorectal Cancer Control Program (CRCCP) in 2009 with the goal of
      increasing CRC screening rates to 80% by 2014. A total of 29 grantees (states and
      tribal organizations) receive CRCCP funding to (1) screen uninsured adults and
      (2) promote CRC screening at the population level. PURPOSE: CRCCP encourages
      grantees to use one or more of five evidence-based interventions (EBIs)
      recommended by the Guide to Community Preventive Services. The purpose of the
      study was to evaluate grantees' EBI use. METHODS: A web-based survey was
      conducted in 2011 measuring grantees' use of CRC screening EBIs and identifying
      their implementation partners. Data were analyzed in 2012. RESULTS: Twenty-eight
      grantees (97%) completed the survey. Most respondents (96%) used small media.
      Fewer used client reminders (75%); reduction of structural barriers (50%);
      provider reminders (32%); or provider assessment and feedback (50%). Provider
      oriented EBIs were rated as harder to implement than client-oriented EBIs.
      Grantees partnered with several types of organizations to implement EBIs, many
      with county- or state-wide reach. CONCLUSIONS: Almost all grantees implement EBIs
      to promote CRC screening, but the EBIs that may have the greatest impact with CRC
      screening are implemented by fewer grantees in the first 2 years of the CRCCP.

PMID- 24139780
TI  - Physical activity and the prevention of depression: a systematic review of
      prospective studies.
AB  - CONTEXT: Given its high prevalence and impact on quality of life, more research
      is needed in identifying factors that may prevent depression. This review
      examined whether physical activity (PA) is protective against the onset of
      depression. EVIDENCE ACQUISITION: A comprehensive search was conducted up until
      December 2012 in the following databases: MEDLINE, Embase, PubMed, PsycINFO,
      SPORTDiscus, and Cochrane Database of Systematic Reviews. Data were analyzed
      between July 2012 and February 2013. Articles were chosen for the review if the
      study used a prospective-based, longitudinal design and examined relationships
      between PA and depression over at least two time intervals. A formal quality
      assessment for each study also was conducted independently by the two reviewers.
      EVIDENCE SYNTHESIS: The initial search yielded a total of 6363 citations. After a
      thorough selection process, 30 studies were included for analyses. Among these,
      25 studies demonstrated that baseline PA was negatively associated with a risk of
      subsequent depression. The majority of these studies were of high methodologic
      quality, providing consistent evidence that PA may prevent future depression.
      There is promising evidence that any level of PA, including low levels (e.g.,
      walking <150 minutes/weeks), can prevent future depression. CONCLUSIONS: From a
      population health perspective, promoting PA may serve as a valuable mental health
      promotion strategy in reducing the risk of developing depression.

PMID- 24139781
TI  - Financial incentives for exercise adherence in adults: systematic review and meta
      analysis.
AB  - CONTEXT: Less than 5% of U.S. adults accumulate the required dose of exercise to
      maintain health. Behavioral economics has stimulated renewed interest in economic
      based, population-level health interventions to address this issue. Despite
      widespread implementation of financial incentive-based public health and
      workplace wellness policies, the effects of financial incentives on exercise
      initiation and maintenance in adults remain unclear. EVIDENCE ACQUISITION: A
      systematic search of 15 electronic databases for RCTs reporting the impact of
      financial incentives on exercise-related behaviors and outcomes was conducted in
      June 2012. A meta-analysis of exercise session attendance among included studies
      was conducted in April 2013. A qualitative analysis was conducted in February
      2013 and structured along eight features of financial incentive design. EVIDENCE
      SYNTHESIS: Eleven studies were included (N=1453; ages 18-85 years and 50%
      female). Pooled results favored the incentive condition (z=3.81, p<0.0001).
      Incentives also exhibited significant, positive effects on exercise in eight of
      the 11 included studies. One study determined that incentives can sustain
      exercise for longer periods (>1 year), and two studies found exercise adherence
      persisted after the incentive was withdrawn. Promising incentive design feature
      attributes were noted. Assured, or "sure thing," incentives and objective
      behavioral assessment in particular appear to moderate incentive effectiveness.
      Previously sedentary adults responded favorably to incentives 100% of the time
      (n=4). CONCLUSIONS: The effect estimate from the meta-analysis suggests that
      financial incentives increase exercise session attendance for interventions up to
      6 months in duration. Similarly, a simple count of positive (n=8) and null (n=3)
      effect studies suggests that financial incentives can increase exercise adherence
      in adults in the short term (<6 months).

PMID- 24139782
TI  - Improving the potential effectiveness of gun buyback programs.

PMID- 24139783
TI  - Avoiding errors in the medical literature: an editor's perspective.

PMID- 24139784
TI  - The mental health and quality of life of adult patients with congenital heart
      disease.
AB  - BACKGROUND: The quality of life (QoL) of adults with congenital heart disease
      (CHD) has gained significant interest. In addition to medical problems, many
      patients with CHD face psychosocial, educational, and behavioral challenges.
      However, few studies have examined the relationship between disease severity and
      QoL in adults with CHD. METHODS: Eighty-five patients (50 men, 35 women) aged 20
      52 years (median, 26.5 years) were enrolled. Patients underwent a QoL, Beck
      Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) survey. The scores
      were compared with those of age- and gender-matched population data according to
      the degree of underlying CHD. Disease severity was classified in relation to
      initial diagnosis, illness course, and current functional status (New York Heart
      Association [NYHA] class, ability index, CHD functional index, ventricular
      ejection fraction, and peak VO2). RESULTS: There was no significant correlation
      between disease severity and current functional status assessed by BDI and BAI.
      Patients who stated that they were religious had better scores for resilience
      (p=0.031), physical QoL (p=0.008), and environmental QoL (p=0.025). Environmental
      QoL scores were higher in patients who fully understood their disease (p=0.004).
      Current NYHA functional class was associated with scores for psychological
      resilience. CONCLUSIONS: CHD severity had a detrimental impact on resilience only
      when measured in terms of poor functional status. The initial diagnosis and
      course of the illness influence QoL and perceived health. Good psychosocial
      adaptation could be the result of close family relationships and involvement,
      making mental adjustment easier.

PMID- 24139785
TI  - The wealth of nations and the dissemination of cardiovascular research.
AB  - BACKGROUND: This study aimed at understanding whether investigators from less
      wealthy countries were at a disadvantage in disseminating their research, after
      accounting for potential differences in research quality and infrastructure.
      METHODS AND RESULTS: In this bibliometric analysis a representative random
      selection of 10% (n=1002 studies) of all abstracts submitted to the European
      Society of Cardiology (ESC) congress 2006 was followed for publication and
      citation from September 2006 to December 2011. The main variable of interest was
      the per-capita gross domestic product (GDP) of the country of the principal
      investigator. Using multivariable models that adjusted for socioeconomic
      indicators and previously identified markers of research quality, we examined the
      relationship between per-capita GDP and three study endpoints: Acceptance at the
      ESC congress, full-text publication, and number of two-year citations. Among 1002
      abstracts from 63 countries, per-capita GDP was positively correlated with all
      three study endpoints. After adjusting for markers of research quality and
      infrastructure, per-capita GDP remained a strong predictor for acceptance at the
      ESC congress (adjusted OR for every 10,000 USD increase in per-capita GDP, 1.44;
      95% CI, 1.15 to 1.80), full-text publication within 5years (adjusted OR, 1.49;
      95% CI, 1.17 to 1.90), and high citation frequency (adjusted OR, 2.30; 95% CI,
      1.31 to 4.04). These findings were largely consistent in a subgroup of abstracts
      of high-quality, prospective clinical trials. CONCLUSION: Investigators in less
      wealthy countries face challenges to disseminate their research, even after
      accounting for potential differences in the quality of their work and research
      infrastructure.

PMID- 24139786
TI  - Editorial for "biosensor technologies".

PMID- 24139787
TI  - Maxillary bone myxoma.
AB  - INTRODUCTION: Maxillary bone myxoma is a rare benign mesenchymal tumor, slow
      growing but locally aggressive. Pathogenesis remains disputed. OBJECTIVE: To
      study the clinical, radiological and histological features and treatment of
      maxillary myxoma, based on a pediatric case report. CASE REPORT: An infant of two
      and a half months presented with endonasal tumor extending to ethmoid. Surgical
      excision was performed on an endonasal approach. Myxoma was diagnosed by
      histologic examination of the surgical specimen, whereas initial biopsy had
      suggested fibrous dysplasia. No recurrence was observed after two and a half
      years' surveillance. CONCLUSION: Positive diagnosis of maxillary myxoma is
      histological. Treatment is primarily surgical. Strict long-term surveillance is
      required because of the high risk of recurrence.

PMID- 24139788
TI  - 'Catching chlamydia': combining cash incentives and community pharmacy access for
      increased chlamydia screening, the view of young people.
AB  - In Australia and elsewhere, chlamydia screening rates for those aged between 16
      and 30 years continue to be low. Innovative, age-appropriate approaches are
      necessary to increase chlamydia screening among this target group to prevent
      short- and long-term consequences of the infection such as pelvic inflammatory
      disease, chronic pelvic pain, ectopic pregnancy and infertility. Studies have
      demonstrated that offering chlamydia screening in community pharmacies may be a
      useful adjunct to current screening services. Approximately 90% of Australians
      visit a pharmacy at least once a year. Chlamydia screening and education in
      community pharmacies with remuneration may provide another option for
      opportunistic testing as part of a national chlamydia screening scheme.
      Compensation is an accepted practice in the field of research and has been
      demonstrated to improve adherence to health promotion activities. In 2011, a
      cross-sectional study of community pharmacy-based chlamydia screening offered in
      conjunction with an A$10 cash incentive to participate was conducted in the
      Australian Capital Territory. As part of this study young people were asked about
      their experience of, and views about, pharmacy-based chlamydia screening. The
      views of consented participants were collected using the one-page questionnaire
      consisting of 10 closed questions and one open-ended question. Participants
      completed the questionnaire when they returned their urine sample and before
      being given the cash incentive. Overall participants were highly satisfied with
      the pharmacy-based chlamydia screening service. Over 60% of questionnaire
      respondents felt that the payment did affect their decision to have the chlamydia
      test, and 23% stated that it made no difference. Young people reported that
      pharmacy-based screening is acceptable and convenient. Accessibility and the
      small cash incentive played significant roles in increasing participation. 

PMID- 24139789
TI  - How much worse will my voiding symptoms get over time?

PMID- 24139790
TI  - Are osteotomies necessary for bladder exstrophy closure?

PMID- 24139791
TI  - Editorial comment.

PMID- 24139792
TI  - How far have we come in interstitial cystitis and how far to go? A
      methodologist's perspective.

PMID- 24139793
TI  - Re: impact of statin use on oncologic outcomes in patients with urothelial
      carcinoma of the bladder treated with radical cystectomy: R. D. Da silva, e.
      Xylinas, L. Kluth, j. J. Crivelli, j. Chrystal, d. Chade, g. B. Guglielmetti, a.
      Pycha, y. Lotan, p. I. Karakiewicz, m. Sun, h. Fajkovic, m. Zerbib, d. S. Scherr
      and s. F. Shariat j urol 2013; 190: 487-492.

PMID- 24139794
TI  - Olive baboons: a non-human primate model for testing dengue virus type 2
      replication.
AB  - OBJECTIVE: This study evaluated the use of a non-human primate, the olive baboon
      (Papio anubis), as a model of dengue infection. Olive baboons closely resemble
      humans genetically and physiologically and have been used extensively for
      assessing novel vaccine formulations. METHODS: Two doses of dengue virus type 2
      (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green
      monkeys received the same quantity of virus and acted as positive controls.
      RESULTS: Following exposure, high levels of viremia were detected in both animal
      species. There was a trend to detect more days of viremia and more homogeneous
      viral titers in animals receiving the low viral dose. In addition, baboons
      infected with the virus generally exhibited positive virus isolation 1 day later
      than African green monkeys. Humoral responses consisting of antiviral and
      neutralizing antibodies were detected in all animals after infection.
      CONCLUSIONS: We conclude that baboons provide an alternative non-human primate
      species for experimental DENV-2 infection and we recommend their use for further
      tests of vaccines, administering the lowest dose assayed: 10(3) pfu.

PMID- 24139795
TI  - A DNA-centric protein interaction map of ultraconserved elements reveals
      contribution of transcription factor binding hubs to conservation.
AB  - Ultraconserved elements (UCEs) have been the subject of great interest because of
      their extreme sequence identity and their seemingly cryptic and largely
      uncharacterized functions. Although in vivo studies of UCE sequences have
      demonstrated regulatory activity, protein interactors at UCEs have not been
      systematically identified. Here, we combined high-throughput affinity
      purification, high-resolution mass spectrometry, and SILAC quantification to map
      intrinsic protein interactions for 193 UCE sequences. The interactome contains
      over 400 proteins, including transcription factors with known developmental
      roles. We demonstrate based on our data that UCEs consist of strongly conserved
      overlapping binding sites. We also generated a fine-resolution interactome of a
      UCE, confirming the hub-like nature of the element. The intrinsic interactions
      mapped here are reflected in open chromatin, as indicated by comparison with
      existing ChIP data. Our study argues for a strong contribution of protein-DNA
      interactions to UCE conservation and provides a basis for further functional
      characterization of UCEs.

PMID- 24139796
TI  - Architecture of the Lsm1-7-Pat1 complex: a conserved assembly in eukaryotic mRNA
      turnover.
AB  - The decay of mRNAs is a key step in eukaryotic gene expression. The cytoplasmic
      Lsm1-7-Pat1 complex is a conserved component of the 5'-to-3' mRNA decay pathway,
      linking deadenylation to decapping. Lsm1-7 is similar to the nuclear Sm complexes
      that bind oligo-uridine tracts in snRNAs. The 2.3 A resolution structure of S.
      cerevisiae Lsm1-7 shows the presence of a heptameric ring with Lsm1-2-3-6-5-7-4
      topology. A distinct structural feature of the cytoplasmic Lsm ring is the C
      terminal extension of Lsm1, which plugs the exit site of the central channel and
      approaches the RNA binding pockets. The 3.7 A resolution structure of Lsm1-7
      bound to the C-terminal domain of Pat1 reveals that Pat1 recognition is not
      mediated by the distinguishing cytoplasmic subunit, Lsm1, but by Lsm2 and Lsm3.
      These results show how the auxiliary domains and the canonical Sm folds of the
      Lsm1-7 complex are organized in order to mediate and modulate macromolecular
      interactions. 

PMID- 24139797
TI  - TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical
      pain hypersensitivity in mice.
AB  - C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated
      primary sensory neurons. These neurons convey two opposite aspects of touch
      sensation: a sensation of pleasantness, and a sensation of injury-induced
      mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs.
      Genetic labeling in combination with electrophysiological recordings show that
      TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice
      exhibit enhanced mechanical and chemical hypersensitivity following inflammation
      and nerve injury as well as increased excitability of spinal cord lamina IIi
      neurons, which could be reversed by intrathecal or bath application of
      recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration
      of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity,
      suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide
      insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and
      controls the threshold of somatic sensation. 

PMID- 24139798
TI  - Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a
      neuroendocrine tumor model.
AB  - The extracellular matrix molecule tenascin-C (TNC) is a major component of the
      cancer-specific matrix, and high TNC expression is linked to poor prognosis in
      several cancers. To provide a comprehensive understanding of TNC's functions in
      cancer, we established an immune-competent transgenic mouse model of pancreatic
      beta-cell carcinogenesis with varying levels of TNC expression and compared
      stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show
      that TNC promotes tumor cell survival, the angiogenic switch, more and leaky
      vessels, carcinoma progression, and lung micrometastasis. TNC downregulates
      Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber
      formation, activates Wnt signaling, and induces Wnt target genes in tumor and
      endothelial cells. Our results implicate DKK1 downregulation as an important
      mechanism underlying TNC-enhanced tumor progression through the provision of a
      proangiogenic tumor microenvironment. 

PMID- 24139799
TI  - Identification of Lgr5-independent spheroid-generating progenitors of the mouse
      fetal intestinal epithelium.
AB  - Immortal spheroids were generated from fetal mouse intestine using the culture
      system initially developed to culture organoids from adult intestinal epithelium.
      Spheroid proportion progressively decreases from fetal to postnatal period, with
      a corresponding increase in production of organoids. Like organoids, spheroids
      show Wnt-dependent indefinite self-renewing properties but display a poorly
      differentiated phenotype reminiscent of incompletely caudalized progenitors. The
      spheroid transcriptome is strikingly different from that of adult intestinal stem
      cells, with minimal overlap of Wnt target gene expression. The receptor LGR4, but
      not LGR5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two
      markers highly enriched in spheroids, are expressed throughout the embryonic-day
      14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing
      using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroid-generating cells as
      developmental progenitors involved in generation of the prenatal intestinal
      epithelium. Ex vivo, spheroid cells have the potential to differentiate into
      organoids, qualifying as a fetal type of intestinal stem cell. 

PMID- 24139800
TI  - mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1/2, to
      regulate neural stem cell self-renewal in vivo.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) integrates signals important
      for cell growth, and its dysregulation in neural stem cells (NSCs) is implicated
      in several neurological disorders associated with abnormal neurogenesis and brain
      size. However, the function of mTORC1 on NSC self-renewal and the downstream
      regulatory mechanisms are ill defined. Here, we found that genetically decreasing
      mTORC1 activity in neonatal NSCs prevented their differentiation, resulting in
      reduced lineage expansion and aborted neuron production. Constitutive activation
      of the translational repressor 4E-BP1, which blocked cap-dependent translation,
      had similar effects and prevented hyperactive mTORC1 induction of NSC
      differentiation and promoted self-renewal. Although 4E-BP2 knockdown promoted NSC
      differentiation, p70 S6 kinase 1 and 2 (S6K1/S6K2) knockdown did not affect NSC
      differentiation but reduced NSC soma size and prevented hyperactive mTORC1
      induced increase in soma size. These data demonstrate a crucial role of mTORC1
      and 4E-BP for switching on and off cap-dependent translation in NSC
      differentiation. 

PMID- 24139801
TI  - Global splicing pattern reversion during somatic cell reprogramming.
AB  - Alternative splicing generates multiple transcripts from a single gene, and cell
      type-specific splicing profiles are important for the properties and functions of
      the cells. Recently, somatic cells have been shown to undergo dedifferentiation
      after the forced expression of transcription factors. However, it remains unclear
      whether somatic cell splicing is reorganized during reprogramming. Here, by
      combining deep sequencing with high-throughput absolute qRT-PCR, we show that
      somatic splicing profiles revert to pluripotent ones during reprogramming.
      Remarkably, the splicing pattern in pluripotent stem cells resembles that in
      testes, and the regulatory regions have specific characteristics in length and
      sequence. Furthermore, our siRNA screen has identified RNA-binding proteins that
      regulate splicing events in iPSCs. We have then demonstrated that two of the RNA
      binding proteins, U2af1 and Srsf3, play a role in somatic cell reprogramming. Our
      results indicate that the drastic alteration in splicing represents part of the
      molecular network involved in the reprogramming process. 

PMID- 24139802
TI  - Pluripotent stem cell protein Sox2 confers sensitivity to LSD1 inhibition in
      cancer cells.
AB  - Gene amplification of Sox2 at 3q26.33 is a common event in squamous cell
      carcinomas (SCCs) of the lung and esophagus, as well as several other cancers.
      Here, we show that the expression of LSD1/KDM1 histone demethylase is
      significantly elevated in Sox2-expressing lung SCCs. LSD1-specific inhibitors
      selectively impair the growth of Sox2-expressing lung SCCs, but not that of Sox2
      negative cells. Sox2 expression is associated with sensitivity to LSD1 inhibition
      in lung, breast, ovarian, and other carcinoma cells. Inactivation of LSD1 reduces
      Sox2 expression, promotes G1 cell-cycle arrest, and induces genes for
      differentiation by selectively modulating the methylation states of histone H3 at
      lysines 4 (H3K4) and 9 (H3K9). Reduction of Sox2 further suppresses Sox2
      dependent lineage-survival oncogenic potential, elevates trimethylation of
      histone H3 at lysine 27 (H3K27) and enhances growth arrest and cellular
      differentiation. Our studies suggest that LSD1 serves as a selective epigenetic
      target for therapy in Sox2-expressing cancers. 

PMID- 24139803
TI  - CDIP1-BAP31 complex transduces apoptotic signals from endoplasmic reticulum to
      mitochondria under endoplasmic reticulum stress.
AB  - Resolved endoplasmic reticulum (ER) stress response is essential for
      intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis.
      Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal
      transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor
      associated protein 31 (BAP31) as an interacting partner of CDIP1. Upon ER stress,
      CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We
      also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER
      stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31
      CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid) and caspase-8
      activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice
      leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data
      demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis
      pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for
      ER-stress-mediated apoptosis signaling. 

PMID- 24139805
TI  - Human bone marrow mesenchymal stem cells regulate biased DNA segregation in
      response to cell adhesion asymmetry.
AB  - Biased DNA segregation is a mitotic event in which the chromatids carrying the
      original template DNA strands and those carrying the template copies are not
      segregated randomly into the two daughter cells. Biased segregation has been
      observed in several cell types, but not in human mesenchymal stem cells (hMSCs),
      and the factors affecting this bias have yet to be identified. Here, we have
      investigated cell adhesion geometries as a potential parameter by plating hMSCs
      from healthy donors on fibronectin-coated micropatterns. On symmetric
      micropatterns, the segregation of sister chromatids to the daughter cells
      appeared random. In contrast, on asymmetric micropatterns, the segregation was
      biased. This sensitivity to asymmetric extracellular cues was reproducible in
      cells from all donors but was not observed in human skin-derived fibroblasts or
      in a fibroblastic cell line used as controls. We conclude that the asymmetry of
      cell adhesion is a major factor in the regulation of biased DNA segregation in
      hMSCs. 

PMID- 24139804
TI  - A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a
      suppressor of melanoma invasion.
AB  - Melanoma is one of the most aggressive types of human cancers, and the mechanisms
      underlying melanoma invasive phenotype are not completely understood. Here, we
      report that expression of guanosine monophosphate reductase (GMPR), an enzyme
      involved in de novo biosynthesis of purine nucleotides, was downregulated in the
      invasive stages of human melanoma. Loss- and gain-of-function experiments
      revealed that GMPR downregulates the amounts of several GTP-bound (active) Rho
      GTPases and suppresses the ability of melanoma cells to form invadopodia, degrade
      extracellular matrix, invade in vitro, and grow as tumor xenografts in vivo.
      Mechanistically, we demonstrated that GMPR partially depletes intracellular GTP
      pools. Pharmacological inhibition of de novo GTP biosynthesis suppressed whereas
      addition of exogenous guanosine increased invasion of melanoma cells as well as
      cells from other cancer types. Our data identify GMPR as a melanoma invasion
      suppressor and establish a link between guanosine metabolism and Rho-GTPase
      dependent melanoma cell invasion. 

PMID- 24139806
TI  - Two Wnts instruct topographic synaptic innervation in C. elegans.
AB  - Gradients of topographic cues play essential roles in the organization of sensory
      systems by guiding axonal growth cones. Little is known about whether there are
      additional mechanisms for precise topographic mapping of synaptic connections.
      Whereas the C. elegans DA8 and DA9 neurons have similar axonal trajectories,
      their synapses are positioned in distinct but adjacent domains in the anterior
      posterior axis. We found that two Wnts, LIN-44 and EGL-20, are responsible for
      this spatial organization of synapses. Both Wnts form putative posterior-high,
      anterior-low gradients. The posteriorly expressed LIN-44 inhibits synapse
      formation in both DA9 and DA8, and creates a synapse-free domain on both axons
      via LIN-17 /Frizzled. EGL-20, a more anteriorly expressed Wnt, inhibits synapse
      formation through MIG-1/Frizzled, which is expressed in DA8 but not in DA9. The
      Wnt-Frizzled specificity and selective Frizzled expression dictate the
      stereotyped, topographic positioning of synapses between these two neurons.

PMID- 24139808
TI  - Multimodal neuroimaging investigations of alterations to consciousness: the
      relationship between absence epilepsy and sleep.
AB  - The link between epilepsy and sleep is well established on many levels. The focus
      of the current review is on recent neuroimaging investigations into the
      alterations of consciousness that are observed during absence seizures and the
      descent into sleep. Functional neuroimaging provides simultaneous cortical and
      subcortical recording of activity throughout the brain, allowing a detailed
      definition and characterization of large-scale brain networks and the
      interactions between them. This has led to the identification of a set of regions
      which collectively form the consciousness system, which includes contributions
      from the default mode network (DMN), ascending arousal systems, and the thalamus.
      Electrophysiological and neuroimaging investigations have also clearly
      demonstrated the importance of thalamocortical and corticothalamic networks in
      the evolution of sleep and absence epilepsy, two phenomena in which the subject
      experiences an alteration to the conscious state and a disconnection from
      external input. However, the precise relationship between the consciousness
      system, thalamocortical networks, and consciousness itself remains to be
      clarified. One of the fundamental challenges is to understand how distributed
      brain networks coordinate their activity in order to maintain and implement
      complex behaviors such as consciousness and how modifications to this network
      activity lead to alterations in consciousness. By taking into account not only
      the level of activation of individual brain regions but also their connectivity
      within specific networks and the activity and connectivity of other relevant
      networks, a more specific quantification of brain states can be achieved. This,
      in turn, may provide a more fundamental understanding of the alterations to
      consciousness experienced in sleep and epilepsy.

PMID- 24139809
TI  - Novel urinary markers for detection of bladder cancer-are we failing?

PMID- 24139807
TI  - Genomic biomarkers of SUDEP in brain and heart.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy
      related mortality, but how to predict which patients are at risk and how to
      prevent it remain uncertain. The underlying pathomechanisms of SUDEP are still
      largely unknown, but the general consensus is that seizures somehow disrupt
      normal cardiac or respiratory physiology leading to death. However, the
      proportion of SUDEP cases exhibiting cardiac or respiratory dysfunction as a
      critical factor in the terminal cascade of events remains unresolved. Although
      many general risk factors for SUDEP have been identified, the development of
      reliable patient-specific biomarkers for SUDEP is needed to provide more accurate
      risk prediction and personalized patient management strategies. Studies in animal
      models and patient groups have revealed at least nine different brain-heart genes
      that may contribute to a genetic susceptibility for SUDEP, making them
      potentially useful as genomic biomarkers. This review summarizes data on the
      relationship between these neurocardiac genes and SUDEP, discussing their brain
      heart expression patterns and genotype-phenotype correlations in mouse models and
      people with epilepsy. These neurocardiac genes represent good first candidates
      for evaluation as genomic biomarkers of SUDEP in future studies. The development
      of validated reliable genomic biomarkers for SUDEP has the potential to transform
      the clinical treatment of epilepsy by pinpointing patients at risk of SUDEP and
      allowing optimized, genotype-guided therapeutic and prevention strategies.

PMID- 24139810
TI  - Functional reorganization of neural networks during repeated exposure to the
      traumatic memory in posttraumatic stress disorder: an exploratory fMRI study.
AB  - BACKGROUND: Repeated exposure to the traumatic memory (RETM) is a common
      component of treatments for posttraumatic stress disorder (PTSD). This treatment
      is based on a fear extinction model; however, the degree to which this treatment
      actually engages and modifies neural networks mediating fear extinction is
      unknown. Therefore, the purpose of the current exploratory study was to define
      the dynamic changes in neural processing networks while participants completed a
      novel adaptation of RETM. METHOD: Participants were adult women (N = 16) with
      PTSD related to physical or sexual assault. Prior to scanning, participants
      provided written narratives of a traumatic event related to their PTSD as well as
      a neutral control event. RETM during fMRI consisted of 5 sequential presentations
      of the blocked narrative types, lasting three minutes each. Self-reported anxiety
      was assessed after each presentation. RESULTS: Relative to changes in functional
      connectivity during the neutral control script, RETM was associated with
      strengthened functional connectivity of the right amygdala with the right
      hippocampus and right anterior insular cortex, left amygdala with the right
      insular cortex, medial PFC with right anterior insula, left hippocampus with
      striatum and dorsal cingulate cortex, and right hippocampus with striatum and
      orbitofrontal cortex. Greater PTSD severity generally led to less changes in
      functional connectivity with the right insular cortex. CONCLUSIONS: These results
      provide evidence that RETM engages and modifies functional connectivity pathways
      with neural regions implicated in fear extinction. The results also implicate the
      engagement of the right insular cortex and striatum during RETM and suggest their
      importance in human fear extinction to trauma memories. However, comorbidity in
      the sample and the lack of a control group limit inferences regarding RETM with
      PTSD populations specifically.

PMID- 24139811
TI  - Patterns of tobacco-related mortality among individuals diagnosed with
      schizophrenia, bipolar disorder, or depression.
AB  - Even though individuals with psychiatric conditions have a prevalence of smoking
      approximately 2-4 times greater than the general population, surprisingly little
      evidence exists to inform an assessment of the full range of tobacco-related
      mortality in such populations. The current study aims to provide mortality
      estimates for conditions causally related to tobacco use among individuals
      hospitalized with a primary psychiatric diagnosis in California from 1990 to
      2005. Restricting cases to those of individuals aged 35 or older at the mid-point
      of their follow-up period, we assembled cohorts of individuals with ICD-9
      diagnoses of schizophrenia and related disorders ("schizophrenia"; n = 174,277),
      depressive disorders (n = 338,250), or bipolar disorder (n = 78,739). Inpatient
      records were linked to death-certificate data. We generated age-, sex-, and race
      adjusted standardized mortality ratios (SMRs) for the 19 diseases identified by
      the Centers for Disease Control and Prevention as being causally linked to
      tobacco use. The SMRs for all tobacco-linked diseases combined were:
      schizophrenia, 2.45 (95% CI = 2.41-2.48); bipolar, 1.57 (95% CI = 1.53-1.62); and
      depression, 1.95 (95% CI = 1.93-1.98). Tobacco-related conditions comprised
      approximately 53% (23,620/44,469) of total deaths in the schizophrenia, 48%
      (6004/12,564) in the bipolar, and 50% (35,729/71,058) in the depression cohorts.
      Addressing tobacco use in psychiatric populations is a critical clinical and
      public-health concern, especially in light of the currently limited clinical
      attention devoted to tobacco use in these groups.

PMID- 24139812
TI  - Klinefelter syndrome and risk of psychosis, autism and ADHD.
AB  - BACKGROUND: Schizophrenia, bipolar disorder, autism spectrum disorders and ADHD
      might be overrepresented in Klinefelter syndrome, but previous investigations
      have yielded inconclusive results. METHODS: We compared a national sample of 860
      Klinefelter patients in Sweden with 86 000 matched population controls. To assess
      the risks of schizophrenia, bipolar disorder, autism spectrum disorder and ADHD
      in Klinefelter patients, we estimated odds ratios and 95% confidence intervals
      using conditional logistic regressions. RESULTS: Klinefelter patients had almost
      four times higher risks of schizophrenia, odds ratio (OR) = 3.6, 95% confidence
      interval (CI) 2.0-6.7 and bipolar disorder (OR = 3.8, CI 1.8-7.6) and about six
      times higher risk of autism spectrum disorder (OR = 6.2, CI 4.0-9.4) and ADHD (OR
      = 5.6, CI 4.0-7.8). CONCLUSIONS: The risk of psychosis, autism and ADHD is
      increased in Klinefelter patients. These findings indicate an X chromosome
      related factor in the etiology of the studied psychiatric disorders, and may also
      have implications for treatment of patients with Klinefelter syndrome.

PMID- 24139813
TI  - Factors contributing to inherent varus alignment of lower limb in normal Asian
      adults: role of tibial plateau inclination.
AB  - PURPOSE: This prospective study aimed to evaluate radiographically, mechanical or
      hip-knee-ankle (HKA) axis in healthy, asymptomatic, Asian (Indian and Korean)
      adults between 20 and 40 years of age to determine the incidence of inherent
      varus (mechanical limb alignment of >3 degrees  varus) and the factors
      influencing it. METHODS: Three hundred and eighty-eight lower limbs were
      evaluated using full length, standing hip-to-ankle radiographs in 198 healthy,
      asymptomatic, Asian (Indian and Korean) adults between 20 and 40 years of age to
      assess the hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA),
      femoral bowing and femoral neck-shaft angle to determine the incidence of
      inherent varus (mechanical limb alignment of >3 degrees  varus) and the factors
      influencing it. RESULTS: Overall, the mean HKA angle was 177.6 degrees +/-2.6
      degrees  with 34.5% of limbs in inherent varus (mean HKA angle 174.9 degrees +/
      1.8 degrees ). The incidence of inherent varus was significantly higher (p=0.01)
      in males (40%) compared to females (28%) but similar among Indian (34%) and
      Korean subjects (35%). The hip-knee-ankle (HKA) angle showed significant positive
      correlation (r=0.82, p<0.001) with only the medial proximal tibial angle (MPTA).
      CONCLUSIONS: Inherent varus alignment of the lower limb is fairly common among
      asymptomatic, Asian adults. These results raise several pertinent questions
      regarding the role of inherent varus in the aetiopathogenesis of knee
      osteoarthritis and in lower limb realignment procedures.

PMID- 24139814
TI  - [Is the IVF/ICSI sequence with fresh transfer soon to be obsolete? Innovation in
      MAP: freezing of all embryos].

PMID- 24139815
TI  - [Laparoscopic radical hysterectomy after initial brachytherapy for stage IB1
      cervical cancer: feasibility and results].
AB  - BACKGROUND: The aim of this study was to examine the feasibility and to report
      the results of laparoscopic radical hysterectomy (LRH) after initial uterovaginal
      brachytherapy (BT) for stage IB1 cervical cancer. PATIENTS AND METHODS: We
      retrospectively reviewed in two Comprehensive Cancer Centers patients who had
      undergone initial BT followed 6 to 8 weeks later by LRH and lymph node
      dissection. RESULTS: Between 2003 and 2010, 162 patients had undergone LRH. The
      procedure was feasible using this approach in 160 (98.8%) cases (2 conversions to
      laparotomy). Eight peroperative complications had occurred. Nineteen patients had
      nodal involvement. Peri- or postoperative ureteral morbidity had occurred in 10
      (6%) patients. Twenty-four (15%) patients had experienced postoperative dysuria.
      Histologically, only 9 patients had residual cervical disease>5 mm and only 1
      patient had parametrial lymphovascular space involvement (associated with nodal
      spread). No patient had vaginal disease or involved surgical margins. After a
      median follow-up of 39 months (range, 3-118), 9 patients had relapsed. Five-year
      overall survival was 95% (88.2%-97.9%). CONCLUSIONS: Radical hysterectomy using a
      laparoscopic approach is feasible and reproducible after initial BT for stage IB1
      cervical cancer and is associated with excellent survival. Morbidity is very
      close to that reported in patients treated using upfront surgery. In this large
      series, the morbidity associated with parametrial dissection and the fact that
      parametrial spread was observed in only 0.6% of the patients suggest that a
      simple extrafascial hysterectomy is perhaps sufficient in this context.

PMID- 24139816
TI  - [Interest of a thrombin and fibrinogen combipatch in preventing breast cancer
      seroma after lymph node dissection].
AB  - OBJECTIVE: To evaluate the effect of combipatch TachoSil((r)) in the prevention
      of seromas after axillary dissection in local breast cancer. PATIENTS ET
      METHODES: A retrospective, case-control study conducted between January 2007 and
      December 2009, in two departments of Obstetrics and Gynecology of the AP-HP.
      Sixty-six patients (45 in the control group and 22 in the group TachoSil((r)))
      who have undergone an axillary dissection alone, with establishment of a redon or
      with lumpectomy, were included. The total amount of lymph drained during the
      stay, the number of days of drainage, duration of hospitalization, the number of
      lymphoceles and the number of retrievals performed at the waning of
      hospitalization were collected. RESULTS: The population was similar in age, body
      mass index (BMI), clinical and pathological data. There was no significant
      difference in terms of total volume of lymph drained (268.2 +/- 220.7 mL without
      TachoSil((r)) and 228.6 +/- 128.8 mL with TachoSil((r)), P = 0.89) and the number
      of days of drainage (3.9 +/- 1.6 days without TachoSil((r)) and 3.1 +/- 0.9 days
      with TachoSil((r)), P = 0.10). The duration of hospitalization was significantly
      higher in the group TachoSil((r)) (5 +/- 1.6 days with TachoSil((r)) and 3.8 +/-
      1.1 days without TachoSil((r)), P = 0.006). CONCLUSION: This study shows no
      benefit of combipatch (TachoSil((r))) in prevention of seromas after axillary
      lymph node dissection. A randomized study with large effective is necessary.

PMID- 24139818
TI  - Odor discrimination requires proper olfactory fast oscillations in awake mice.
AB  - Gamma oscillations are commonly observed in sensory brain structures, notably in
      the olfactory bulb. The mechanism by which gamma is generated in the awake rodent
      and its functional significance are still unclear. We combined pharmacological
      and genetic approaches in the awake mouse olfactory bulb to show that gamma
      oscillations required the synaptic interplay between excitatory output neurons
      and inhibitory interneurons. Gamma oscillations were amplified, or abolished,
      after optogenetic activation or selective lesions to the bulbar output neurons.
      In response to a moderate increase of the excitation/inhibition ratio in output
      neurons, long-range gamma synchronization was selectively enhanced while the mean
      firing activity and the amplitude of inhibitory inputs both remained unchanged in
      output neurons. This excitation/inhibition imbalance also impaired odor
      discrimination in an olfactory learning task, suggesting that proper fast
      neuronal synchronization may be critical for the correct discrimination of
      similar sensory stimuli.

PMID- 24139817
TI  - Chronic cellular imaging of entire cortical columns in awake mice using
      microprisms.
AB  - Two-photon imaging of cortical neurons in vivo has provided unique insights into
      the structure, function, and plasticity of cortical networks, but this method
      does not currently allow simultaneous imaging of neurons in the superficial and
      deepest cortical layers. Here, we describe a simple modification that enables
      simultaneous, long-term imaging of all cortical layers. Using a chronically
      implanted glass microprism in barrel cortex, we could image the same
      fluorescently labeled deep-layer pyramidal neurons across their entire
      somatodendritic axis for several months. We could also image visually evoked and
      endogenous calcium activity in hundreds of cell bodies or long-range axon
      terminals, across all six layers in visual cortex of awake mice.
      Electrophysiology and calcium imaging of evoked and endogenous activity near the
      prism face were consistent across days and comparable with previous observations.
      These experiments extend the reach of in vivo two-photon imaging to chronic,
      simultaneous monitoring of entire cortical columns.

PMID- 24139819
TI  - Health in children: a conceptual framework for use in healthy ageing research.
AB  - OBJECTIVE: With increasing life expectancy, there is a focus on "healthy ageing".
      Most activities in this area focus on the elderly. However, the ageing process
      starts much earlier. Childhood offers an important window to lay a base for
      future healthy ageing. Thus, to address the full ageing process, we should
      include younger populations in ageing research. If we aim for healthy ageing
      across the life course, we need to clarify the meaning of health at different
      ages. The aim of this paper was to develop a conceptual framework for child
      health, which can be used as a starting point for healthy ageing research from a
      life course perspective. RESULTS: We conceptualize child health as: "a dynamic
      state, not merely the absence of disease or disability, but also adequate
      resilience that permits optimal physical, mental, and social functioning, and
      optimal quality of life in order to achieve full potential and to become an
      independent, functional, and social individual." We propose five core dimensions
      of child health: Absence of physical disease; absence of psychiatric disorders;
      optimal physical, mental, and social functioning, including adequate development;
      good quality of life or well-being; and adequate resilience. CONCLUSION: This
      conceptualization of child health and its dimensions can be seen as a first step
      towards building a framework for future studies into healthy ageing across the
      life course.

PMID- 24139820
TI  - Dose napkin-ring sign suggest possibility to identify rupture-prone plaque in
      coronary computed tomography angiography?

PMID- 24139821
TI  - Essential N-terminal insertion motif anchors the ESCRT-III filament during MVB
      vesicle formation.
AB  - The endosomal sorting complexes required for transport (ESCRTs) have emerged as
      key cellular machinery that drive topologically unique membrane deformation and
      scission. Understanding how the ESCRT-III polymer interacts with membrane,
      promoting and/or stabilizing membrane deformation, is an important step in
      elucidating this sculpting mechanism. Using a combination of genetic and
      biochemical approaches, both in vivo and in vitro, we identify two essential
      modules required for ESCRT-III-membrane association: an electrostatic cluster and
      an N-terminal insertion motif. Mutating either module in yeast causes cargo
      sorting defects in the MVB pathway. We show that the essential N-terminal
      insertion motif provides a stable anchor for the ESCRT-III polymer. By replacing
      this N-terminal motif with well-characterized membrane insertion modules, we
      demonstrate that the N terminus of Snf7 has been tuned to maintain the
      topological constraints associated with ESCRT-III-filament-mediated membrane
      invagination and vesicle formation. Our results provide insights into the
      spatially unique, ESCRT-III-mediated membrane remodeling.

PMID- 24139823
TI  - Reprint of: DAT genotype modulates striatal processing and long-term memory for
      items associated with reward and punishment.
AB  - Previous studies have shown that appetitive motivation enhances episodic memory
      formation via a network including the substantia nigra/ventral tegmental area
      (SN/VTA), striatum and hippocampus. This functional magnetic resonance imaging
      (fMRI) study now contrasted the impact of aversive and appetitive motivation on
      episodic long-term memory. Cue pictures predicted monetary reward or punishment
      in alternating experimental blocks. One day later, episodic memory for the cue
      pictures was tested. We also investigated how the neural processing of appetitive
      and aversive motivation and episodic memory were modulated by dopaminergic
      mechanisms. To that end, participants were selected on the basis of their
      genotype for a variable number of tandem repeat polymorphism of the dopamine
      transporter (DAT) gene. The resulting groups were carefully matched for the 5
      HTTLPR polymorphism of the serotonin transporter gene. Recognition memory for
      cues from both motivational categories was enhanced in participants homozygous
      for the 10-repeat allele of the DAT, the functional effects of which are not
      known yet, but not in heterozygous subjects. In comparison with heterozygous
      participants, 10-repeat homozygous participants also showed increased striatal
      activity for anticipation of motivational outcomes compared to neutral outcomes.
      In a subsequent memory analysis, encoding activity in striatum and hippocampus
      was found to be higher for later recognized items in 10-repeat homozygotes
      compared to 9/10-repeat heterozygotes. These findings suggest that processing of
      appetitive and aversive motivation in the human striatum involve the dopaminergic
      system and that dopamine plays a role in memory for both types of motivational
      information. In accordance with animal studies, these data support the idea that
      encoding of motivational events depends on dopaminergic processes in the
      hippocampus. 

PMID- 24139822
TI  - Conserved miR-8/miR-200 defines a glial niche that controls neuroepithelial
      expansion and neuroblast transition.
AB  - Neuroepithelial cell proliferation must be carefully balanced with the transition
      to neuroblast (neural stem cell) to control neurogenesis. Here, we show that loss
      of the Drosophila microRNA mir-8 (the homolog of vertebrate miR-200 family)
      results in both excess proliferation and ectopic neuroblast transition.
      Unexpectedly, mir-8 is expressed in a subpopulation of optic-lobe-associated
      cortex glia that extend processes that ensheath the neuroepithelium, suggesting
      that glia cells communicate with the neuroepithelium. We provide evidence that
      miR-8-positive glia express Spitz, a transforming growth factor alpha (TGF-alpha)
      like ligand that triggers epidermal growth factor receptor (EGFR) activation to
      promote neuroepithelial proliferation and neuroblast formation. Further, our
      experiments suggest that miR-8 ensures both a correct glial architecture and the
      spatiotemporal control of Spitz protein synthesis via direct binding to Spitz 3'
      UTR. Together, these results establish glial-derived cues as key regulatory
      elements in the control of neuroepithelial cell proliferation and the neuroblast
      transition. 

PMID- 24139824
TI  - Multinutrient-fortified juices improve vitamin D and vitamin E status in
      children: a randomized controlled trial.
AB  - BACKGROUND: Provision of fortified juices may provide a convenient method to
      maintain and increase blood fat-soluble vitamins. OBJECTIVE: To determine whether
      children consuming orange juice fortified with calcium and combinations of
      vitamins D, E, and A could increase serum 25-hydroxyvitamin D [25(OH)D], alpha
      tocopherol, and retinol levels. DESIGN: A 12-week randomized, double-blind,
      controlled trial. PARTICIPANTS/SETTING: One hundred eighty participants (aged
      8.04+/-1.42 years) were recruited at Tufts (n=70) and Boston University (n=110)
      during 2005-2006. Of those recruited, 176 children were randomized into three
      groups: CaD (700 mg calcium+200 IU vitamin D), CaDEA (700 mg calcium+200 IU
      vitamin D+12 IU vitamin E+2,000 IU vitamin A as beta carotene), or Ca (700 mg
      calcium). Children consumed two 240-mL glasses of CaD, CaDEA, or Ca fortified
      orange juice daily for 12 weeks. MAIN OUTCOME MEASURES: Serum 25(OH)D, alpha
      tocopherol, and retinol concentrations. STATISTICAL ANALYSES: Changes in 25(OH)D,
      alpha-tocopherol, retinol, and parathyroid hormone concentrations were examined.
      Covariates included sex, age, race/ethnicity, body mass index, and baseline
      25(OH)D, alpha-tocopherol, retinol, or parathyroid hormone levels. Multivariate
      models and repeated measures analysis of variance tested for group differences
      with pre-post measures (n=141). RESULTS: Baseline 25(OH)D was 68.4+/-27.7 nmol/L
      (27.4+/-11.10 ng/mL) ), with 21.7% of participants having inadequate 25(OH)D (<50
      nmol/L [20.03 ng/mL]). The CaD group's 25(OH)D increase was greater than that of
      the Ca group (12.7 nmol/L [5.09 ng/mL], 95% CI 1.3 to 24.1; P=0.029). The CaDEA
      group's increase in alpha-tocopherol concentration was greater than that in the
      Ca or CaD groups (3.79 MUmol/L [0.16 MUg/mL], 95% CI 2.5 to 5.1 and 3.09 MUmol/L
      [0.13 MUg/mL], 95% CI -1.8 to 4.3), respectively (P<0.0001). Retinol levels did
      not change, and body weight remained as expected for growth. CONCLUSIONS: Daily
      consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E
      increased 25(OH)D and alpha-tocopherol concentrations in young children within 12
      weeks.

PMID- 24139825
TI  - T-lymphocyte recognition of beta cells in type 1 diabetes: clinical perspectives.
AB  - Type 1 diabetes (T1D) is an autoimmune disease characterized by the activation of
      lymphocytes against pancreatic beta cells. Landmarks in the history of T1D were
      the description of insulitis and of islet cell autoantibodies, and report an
      association between T1D and a limited number of HLA alleles. Another step was the
      study of T-lymphocytes, now known to be central to the disease process of T1D
      whether in mice or men. In humans, T-lymphocytes, and especially CD8+ T-cells,
      are predominant in insulitis. The characterization of antigenic fragments-
      peptides--recognized by T-cells paves the way towards new assays for predicting
      T1D and its prevention using antigen- or peptide-specific immunotherapy, while
      avoiding side effects that may counteract the limited efficacy of
      immunosuppression and immunomodulation in preserving beta-cells from autoimmune
      destruction in recent-onset T1D patients. The current need for new preclinical
      models for testing strategies of antigen-specific immune tolerance is also
      highlighted.

PMID- 24139826
TI  - Basal insulin analogs: from pathophysiology to therapy. What we see, know, and
      try to comprehend?
AB  - During the past 10 years, several new basal insulin analogs have been developed.
      There has been for 3 years controversy on the potential increased risk for cancer
      with insulin glargine, which ceased with the publication of the ORIGIN trial in
      2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend
      that plasma insulin concentrations remain within a 50-200 pmol/L range in order
      to avoid overinsulinization, a potential causative factor for increased
      mitogenicity. Such concentrations are achieved when daily doses of insulin
      glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma
      insulin concentrations are much greater in persons treated with insulin detemir
      and especially insulin degludec. These insulins derive their protracted action
      from the insertion of a long chain fatty acid moiety to the insulin molecule
      thereby increasing albumin binding. As a consequence, in persons with type 2
      diabetes, stable total plasma concentrations as high as either 1600 or 6000
      pmol/L are observed for insulin detemir or degludec, respectively. At present,
      the free to bound ratio of plasma insulin concentrations remains unknown for
      these two compounds. A first requirement is to understand how these insulins are
      eliminated or degraded and secondly to quantify the respective contributions of
      the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized
      clinical trials, a better comprehension of the metabolism of all the new insulins
      would be invaluable.

PMID- 24139827
TI  - Clinical outcome with platinum-based chemotherapy in patients with advanced
      nonsquamous EGFR wild-type non-small-cell lung cancer segregated according to
      KRAS mutation status.
AB  - BACKGROUND: We hypothesized that KRAS mutations function as a marker of poor
      sensitivity to first-line platinum-based chemotherapy in patients with advanced
      nonsquamous EGFR wild-type (WT) non-small-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Consecutive advanced nonsquamous EGFR WT NSCLCs treated at the Medical
      Oncology of Perugia with simultaneous assessment of KRAS mutation status were
      eligible. Anaplastic lymphoma kinase (ALK) gene status was known in roughly half
      of the patients who had KRAS WT. RESULTS: Two hundred four patients were
      included. Among them, the 77 individuals carrying a KRAS-mutant phenotype
      experienced a significantly inferior outcome in terms of response rate (P = .04),
      disease control rate (P = .05), and progression-free survival (PFS) (P = .05)
      compared with the EGFR WT/KRAS WT population. The association between KRAS
      mutation and shorter PFS remained statistically significant at multivariate
      analysis (hazard ratio [HR], 1.45). In addition, patients with KRAS mutations
      reported a significantly shorter overall survival (OS) compared with patients
      with EGFR WT/KRAS WT/ALK negativity (n = 64) (P = .02). Among patients with KRAS
      mutations, those harboring a mutation at codon 13 (n = 12) performed worse than
      those with a mutation at codon 12 (n = 62) in terms of both PFS and OS (P = .09
      for both). CONCLUSION: KRAS mutation appears to negatively affect sensitivity to
      first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR
      WT NSCLC. Studies on larger case series are needed to address differences in
      clinical outcome according to the type of mutation.

PMID- 24139828
TI  - Rapid desensitization of mice with anti-FcgammaRIIb/FcgammaRIII mAb safely
      prevents IgG-mediated anaphylaxis.
AB  - BACKGROUND: Stimulatory IgG receptors (FcgammaRs) on bone marrow-derived cells
      contribute to the pathogenesis of several autoimmune and inflammatory disorders.
      Monoclonal antibodies that block FcgammaRs might suppress these diseases, but
      they can induce anaphylaxis. OBJECTIVE: We wanted to determine whether a rapid
      desensitization approach can safely suppress IgG/FcgammaR-mediated anaphylaxis.
      METHODS: Mice were injected with serially increasing doses of 2.4G2, a rat mAb
      that blocks the inhibitory FcgammaR, FcgammaRIIb, and the stimulatory receptor,
      FcgammaRIII. Rectal temperature was used to detect the development of
      anaphylaxis. Passive and active IgG-mediated anaphylaxis were evaluated in mice
      that had been rapidly desensitized with 2.4G2 or mock-desensitized in mice in
      which monocyte/macrophages, basophils, or neutrophils had been depleted or
      desensitized and in mice in which FcgammaRI, FcgammaRIII, and/or FcgammaRIV had
      been deleted or blocked. RESULTS: Rapid desensitization with 2.4G2 prevented
      2.4G2-induced shock and completely suppressed IgG-mediated anaphylaxis. Rapid
      desensitization of ovalbumin-sensitized mice with 2.4G2 was safer and more
      effective than rapid desensitization with ovalbumin. 2.4G2 treatment completely
      blocked FcgammaRIII and removed most FcgammaRI and FcgammaRIV from nucleated
      peripheral blood cells. Because IgG(2a)-mediated anaphylaxis was partially
      FcgammaRI and FcgammaRIV dependent, the effects of 2.4G2 on FcgammaRI and
      FcgammaRIV were probably crucial for its complete inhibition of IgG(2a)-mediated
      anaphylaxis. IgG(2a)-mediated anaphylaxis was partially inhibited by depletion or
      desensitization of monocyte/macrophages, basophils, or neutrophils. CONCLUSION:
      IgG-mediated anaphylaxis can be induced by ligation of FcgammaRI, FcgammaRIII, or
      FcgammaRIV on monocycte/macrophages, basophils, or neutrophils and can be safely
      suppressed by rapid desensitization with anti-FcgammaRII/RIII mAb. A similar
      approach may safely suppress other FcgammaR-dependent immunopathology.

PMID- 24139829
TI  - An evidence-based analysis of house dust mite allergen immunotherapy: a call for
      more rigorous clinical studies.
AB  - BACKGROUND: According to meta-analyses and reviews, subcutaneous allergen
      immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are beneficial
      in patients with allergic rhinitis (AR) and allergic asthma (AA) induced by house
      dust mites (HDMs). However, the reported effect sizes have varied greatly from
      one study to another. OBJECTIVE: We sought to perform an evidence-based medicine
      assessment of commercially available SCIT and SLIT formulations in patients with
      HDM-induced AA and HDM-induced AR. METHODS: We searched for double-blind, placebo
      controlled randomized clinical trials and analyzed study designs, doses,
      regimens, patient-reported outcomes, safety reporting, and compliance. RESULTS:
      Forty-four studies met our inclusion criteria. Some studies tested both SLIT and
      SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms
      in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in
      patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from
      6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported)
      ranged from 7 to 30 MUg for maintenance doses and 60 to 420 MUg for cumulative
      doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 MUg for
      maintenance doses and 60 to 23,695 MUg for cumulative doses. Safety data were
      often absent or poorly reported. A statistically significant active versus
      placebo symptom score was observed more frequently for SCIT than for SLIT.
      CONCLUSION: There is no consensus on basic treatment parameters (eg, dose and
      duration) in HDM SCIT and SLIT. There is an urgent need for rigorous, long-term,
      double-blind, placebo-controlled randomized clinical trials with an efficacy
      criterion that reflects the particular features of HDM-induced allergic disease.

PMID- 24139830
TI  - Noneosinophilic responders with occupational asthma: a phenotype associated with
      a poor asthma prognosis.

PMID- 24139831
TI  - Differential homeostatic dynamics of human regulatory T-cell subsets following
      neonatal thymectomy.

PMID- 24139832
TI  - Dynamic loading posture of the thumb: the Colditz Tear Test.
AB  - The movement patterns one sees when loads placed on a joint are incrementally
      increased provides valuable insight as to how a joint functions during different
      everyday activities. This author describes a simple, yet effective method of
      assessing the thumb carpometacarpal joint as load demands increase. It may be
      used as an evaluative tool or as an adjunct to treatment.

PMID- 24139833
TI  - Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on
      markers of arterial stiffness.
AB  - Antihypertensive agents may, even within the same class, exert variable effects
      on arterial stiffness variables. Nebivolol could have a better impact than
      atenolol on arterial stiffness, by increasing the bioavailability of endothelium
      derived nitric oxide. Angiotensin-converting enzyme inhibitors (ACEIs) and
      angiotensin receptor blockers (ARBs) increase plasma renin activity (enhancing
      the production of angiotensin II via non-ACE-related pathways) whereas aliskiren
      does not, potentially affecting central hemodynamics differently. We compared the
      effects of two renin-angiotensin-aldosterone system (RAAS) inhibitors (quinapril
      and aliskiren) and 2 beta-blockers (atenolol and nebivolol) on arterial stiffness
      variables. Treatment-naive patients (n = 72; 68.1% males; age, 47.6 +/- 10.6
      years) with uncomplicated stage I-II essential hypertension were randomly
      assigned to quinapril, aliskiren, atenolol, or nebivolol for 10 weeks. Central
      systolic and diastolic blood pressure (BP), central pulse pressure (PP),
      augmentation index (AIx), and pulse wave velocity (PWV) were measured at
      baseline, 2, and 10 weeks. The same measurements were performed in 20
      normotensive subjects (65.0% males; age, 40.0 +/- 8.9 years). Peripheral and
      central systolic and diastolic BP, peripheral PP, and PWV were significantly and
      similarly reduced by all agents. However, PWV continued to decline between the
      second and last visit in patients on quinapril and aliskiren but did not change
      in those on nebivolol or atenolol. Central PP and AIx decreased in patients on
      quinapril, aliskiren, and nebivolol but did not change in those taking atenolol.
      The decrease in central PP and AIx did not differ between patients on quinapril,
      aliskiren, and nebivolol. Despite similar reductions in peripheral BP, atenolol
      is less effective than nebivolol and RAAS inhibitors in improving central
      pulsatile hemodynamics. Aliskiren exerts similar effects on markers of arterial
      stiffness as quinapril. The clinical relevance of these differences remains to be
      established.

PMID- 24139834
TI  - Gadoxetate disodium-enhanced liver MRI: gallbladder opacification patterns during
      hepatobiliary phase.
AB  - OBJECTIVE(S): To describe the different patterns of gallbladder lumen
      opacification on gadoxetate disodium-enhanced liver magnetic resonance imaging
      (MRI). METHODS: One hundred eighty-seven MRI examinations were reviewed by two
      abdominal imaging radiologists who described the different patterns of
      gallbladder opacification, based on comparing the post-contrast to the pre
      contrast images. RESULTS: Four patterns of gallbladder opacification were
      identified, all based on the anti-dependent distribution of the excreted biliary
      contrast inside the gallbladder lumen. Contrast was identified at the level of
      the gallbladder neck, anti-dependant wall, and gallbladder fundus. One
      gallbladder completely filled with contrast. CONCLUSION(S): The opacification of
      the gallbladder lumen follows a distinctive anti-dependent distribution.

PMID- 24139835
TI  - Delayed splenic rupture presenting 70 days following blunt abdominal trauma.
AB  - Delayed splenic rupture following conservative management of splenic injury is an
      extremely rare complication. We report a case of an adult patient who presented
      with delayed splenic rupture necessitating splenectomy, 2 months following blunt
      abdominal trauma. Imaging at the initial presentation demonstrated only minimal
      splenic contusion and the patient was discharge following 24 hours of
      observation.

PMID- 24139836
TI  - Hypovolemic shock complex: does the pancreatic perfusion increase or decrease at
      contrast-enhanced dynamic CT?
AB  - OBJECTIVE: The purpose of this study is to evaluate contrast enhancement effects
      of the pancreas at dynamic computed tomography (CT) to clarify whether pancreatic
      perfusion increases or decreases in severe trauma patients with hypovolemic
      shock. METHODS: A total of 90 patients with (n=30) and without (n=60) blunt
      trauma and hypovolemic shock who underwent dynamic CT for abdomen was included.
      The measurement of CT attenuation values of the pancreas in the early phase and
      the late phase was performed to compare the contrast enhancement effects between
      patients with and without hypovolemic shock. RESULTS: The mean CT attenuation
      values of the pancreas in the early phase of dynamic CT in patients with
      hypovolemic shock [95.4+/-29.1 Hounsfield units (HU)] were significantly lower (P
      < .001) than those in non-hypovolemic patients (136.6+/-17.9 HU), indicating
      decreased pancreatic perfusion in patients with hypovolemic shock. The mean CT
      attenuation values of the pancreas in the late phase of dynamic CT in patients
      with hypovolemic shock (95.9+/-17.6 HU) were significantly higher (P < .026) than
      those in non-hypovolemic patients (87.2+/-9.0 HU), indicating delayed or
      prolonged pancreatic enhancement in patients with hypovolemic shock. CONCLUSIONS:
      Decreased pancreatic perfusion in the early phase and delayed pancreatic
      enhancement in the late phase of contrast-enhanced dynamic CT was a common
      finding in patients with hypovolemic shock.

PMID- 24139837
TI  - Can vaccine legacy explain the British pertussis resurgence?
AB  - Pertussis incidence has been rising in some countries, including the UK, despite
      sustained high vaccine coverage. We questioned whether it is possible to explain
      the resurgence without recourse to complex hypotheses about pathogen evolution,
      subclinical infections, or trends in surveillance efficiency. In particular, we
      investigated the possibility that the resurgence is a consequence of the legacy
      of incomplete pediatric immunization, in the context of cohort structure and age
      dependent transmission. We constructed a model of pertussis transmission in
      England and Wales based on data on age-specific contact rates and historical
      vaccine coverage estimates. We evaluated the agreement between model-predicted
      and observed patterns of age-specific pertussis incidence under a variety of
      assumptions regarding the duration of immunity. Under the assumption that
      infection-derived immunity is complete and lifelong, and regardless of the
      duration of vaccine-induced immunity, the model consistently predicts a
      resurgence of pertussis incidence comparable to that which has been observed.
      Interestingly, no resurgence is predicted when infection- and vaccine-derived
      immunities wane at the same rate. These results were qualitatively insensitive to
      rates of primary vaccine failure. We conclude that the alarming resurgence of
      pertussis among adults and adolescents in Britain and elsewhere may simply be a
      legacy of historically inadequate coverage employing imperfect vaccines. Indeed,
      we argue that the absence of resurgence at this late date would be more
      surprising. Our analysis shows that careful accounting for age dependence in
      contact rates and susceptibility is prerequisite to the identification of which
      features of pertussis epidemiology want additional explanation. 

PMID- 24139838
TI  - Feasibility of post mortem cardiac proton density weighted fast field echo
      imaging in two cases of sudden death.
AB  - OBJECTIVE: The aim of this work is to investigate and compare cardiac proton
      density (PD) weighted fast field echo (FFE) post-mortem magnetic resonance (PMMR)
      imaging with standard cardiac PMMR imaging (T1-weighted and T2-weighted turbo
      spin-echo (TSE)), postmortem CT (PMCT) as well as autopsy. MATERIALS AND METHODS:
      Two human cadavers sequentially underwent cardiac PMCT and PMMR imaging (PD
      weighted FFE, T1-weighted and T2-weighted TSE) and autopsy. The cardiac PMMR
      images were compared to each other as well as to PMCT and autopsy findings.
      RESULTS: For the first case, cardiac PMMR exhibited a focal region of low signal
      in PD-weighted FFE and T2-weighted TSE images, surrounded by a signal intense rim
      in the T2-weighted images. T1-weighted TSE and PMCT did not appear to identify
      any focal abnormality. Macroscopic inspection identified a blood clot; histology
      confirmed this to be a thrombus with an adhering myocardial infarction. In the
      second case, a myocardial rupture with heart tamponade was identified in all PMMR
      images, located at the anterior wall of the left ventricle; PMCT excluded
      additional ruptures. In PD-weighted FFE and T2-weighted TSE images, it occurred
      hypo-intense, while resulting in small clustered hyper-intense spots in T1
      weighted TSE. Autopsy confirmed the PMMR and PMCT findings. CONCLUSIONS:
      Presented initial results have shown PD-weighted FFE to be a valuable imaging
      sequence in addition to traditional T2-weighted TSE imaging for blood clots and
      myocardial haemorrhage with clearer contrast between affected and healthy
      myocardium.

PMID- 24139839
TI  - Combined aberrant expression of Bmi1 and EZH2 is predictive of poor prognosis in
      glioma patients.
AB  - BACKGROUND AND OBJECTIVES: Bmi1 and EZH2 are involved in tumorigenesis of
      gliomas. However, clinicopathologic significance of their expression in gliomas
      is unknown; especially, the prognostic value of combined expression of Bmi1 and
      EZH2 has not been explored. METHODS: Bmi1 and EZH2 expression in human gliomas
      and nonneoplastic brain tissues was measured by immunohistochemistry. RESULTS:
      Both Bmi1 and EZH2 expressions in glioma tissues were significantly higher than
      those in corresponding nonneoplastic brain tissues (both P<0.001). Additionally,
      the upregulations of Bmi1 and EZH2 proteins were both significantly associated
      with advanced WHO grades (both P<0.001) and low KPS (P=0.008 and 0.01,
      respectively). Moreover, the overall survival of patients with high Bmi1 protein
      expression (P=0.006) or high EZH2 protein expression (P=0.01) was obviously lower
      than those with low expressions. More interestingly, glioma patients with
      combined overexpression of Bmi1 and EZH2 proteins had the shortest overall
      survival (P<0.001). Furthermore, multivariate analysis showed that Bmi1n
      expression (P=0.02), EZH2 expression (P=0.03), and combined expression of Bmi1
      and EZH2 (P=0.008), were all independent prognostic factors for overall survival
      in glioma patients. CONCLUSIONS: Our data suggest for the first time that the
      combination of Bmi1 and EZH2 overexpression may be a highly sensitive marker for
      the prognosis in glioma patients.

PMID- 24139840
TI  - Implications of aspirin biochemistry in the pathobiology of ischemic
      cerebrovascular disease.

PMID- 24139841
TI  - Long-term endurance exercise improves aerobic capacity in patients with relapsing
      remitting multiple sclerosis: impact of baseline fatigue.
AB  - Little is known about the sustainability of exercise effects in patients with
      relapsing-remitting Multiple Sclerosis (RRMS). We present the results of a
      prospective, observer-blinded, single-center case control study using a "pre
      post" design including 89 ambulatory patients with RRMS and an EDSS score of
      <=3.5 who participated in an individualized 12 month aerobic endurance exercise
      program. Peak oxygen consumption (VO2 peak) increased and fatigue levels
      decreased significantly over time (p=0.03, p<0.02). Subgroup analysis of patients
      with fatigue (FSS>4) revealed that the increase of VO2 peak remained significant
      after 12 months whereas patients without fatigue did not improve any further
      after six months. A significant decrease of the FSS score was only observed after
      nine months (p<0.03) In conclusion, aerobic exercise leads to a sustainable
      improvement of VO2 peak over an extended exercise period of 12 months. There is a
      weak, but significant effect on fatigue levels which becomes detectable only
      after nine months. Since subgroup analysis revealed that MS patients behaved
      differently according to their baseline fatigue levels, adjustment to the
      individual fatigue levels is recommended for future exercise interventions in
      RRMS patients.

PMID- 24139842
TI  - Madras motor neuron disease (MMND) is distinct from the riboflavin transporter
      genetic defects that cause Brown-Vialetto-Van Laere syndrome.
AB  - INTRODUCTION: Madras motor neuron disease (MMND), MMND variant (MMNDV) and
      Familial MMND (FMMND) have a unique geographic distribution predominantly
      reported from Southern India. The characteristic features are onset in young,
      weakness and wasting of limbs, multiple lower cranial nerve palsies and
      sensorineural hearing loss. There is a considerable overlap in the phenotype of
      MMND with Brown-Vialetto-Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie
      syndrome and Fazio-Londe syndrome. Recently a number of BVVL cases and families
      have been described with mutations in two riboflavin transporter genes SLC52A2
      and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3
      respectively). METHODS AND RESULTS: We describe six families and four sporadic
      MMND cases that have been clinically characterized in detail with history,
      examination, imaging and electrophysiological investigations. We sequenced the
      SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from
      the MMND series as well as the C9ORF72 expansion. No genetic defects were
      identified and the C9ORF72 repeats were all less than 10. CONCLUSIONS: These data
      suggest that MMND is a distinct clinical subgroup of childhood onset MND patients
      where the known genetic defects are so far negative. The clinico-genetic features
      of MMND in comparison with the BVVL group of childhood motor neuron diseases
      suggest that these diseases are likely to share a common defective biological
      pathway that may be a combination of genetic and environmental factors.

PMID- 24139843
TI  - Development of fluorinated CB(2) receptor agonists for PET studies.
AB  - A convergent strategy was followed to modify systematically carbazole based CB(2)
      receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of
      the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and
      Y in 7) were varied systematically. The highest CB(2) affinity was found for the
      2-fluoroethyl substituted carbazole derivative 20a (Ki=5.8nM) containing the
      propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies
      20a fits nicely into the binding pocket of the CB(2) receptor, but elongation of
      the fluoroethyl side chain leads to a different binding mode of the ligands. The
      high CB(2) affinity together with the high selectivity over the CB(2) subtype
      qualifies the fluoroethyl derivative 20a to be developed as a PET tracer.

PMID- 24139844
TI  - Peptide conjugates of 4-aminocyclophosphamide as prodrugs of phosphoramide
      mustard for selective activation by prostate-specific antigen (PSA).
AB  - In our continued effort to develop prodrugs of phosphoramide mustard, conjugates
      of 4-aminocyclophosphamide (4-NH2-CPA) with three PSA-specific peptides were
      synthesized and evaluated as substrates of PSA. These include conjugates of cis
      (2R,4R)-4-NH2-CPA with a tetrapeptide Succinyl-Ser-Lys-Leu-Gln-OH, a hexapeptide
      Succinyl-His-Ser-Ser-Lys-Leu-Gln-OH, and a pentapeptide Glutaryl-Hyp-Ala-Ser-Chg
      Gln-OH. These conjugates were cleaved by PSA efficiently and exclusively after
      the expected glutamine residue to release 4-NH2-CPA, the activated prodrug form
      of phosphoramide mustard. The cleavage was most efficient for the pentapeptide
      conjugate 3 (Glutaryl-Hyp-Ala-Ser-Chg-Gln-NH-CPA), which showed a half-life of 55
      min with PSA, followed by the hexapeptide conjugate 2 (Succinyl-His-Ser-Ser-Lys
      Leu-Gln-NH-CPA) and the tertrapeptide conjugate 1 (Succinyl-Ser-Lys-Leu-Gln-NH
      CPA) with half-lives of 6.5 and 12h, respectively. These results indicate a
      potential of the conjugate 3 as an anticancer prodrug of phosphoramide mustard
      for selective PSA activation.

PMID- 24139845
TI  - Trisubstituted and tetrasubstituted pyrazolines as a novel class of cell-growth
      inhibitors in tumor cells with wild type p53.
AB  - Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra
      substituted pyrazoline were synthesized and tested for their inhibitory effects
      versus the p53(+/+) HCT116 and p53(-/-) H1299 human tumor cell lines. Several
      compounds were active against the two cell lines displaying IC50 values in the
      low micromolar range with a clearly more pronounced effect on the p53(+/+) HCT116
      cells. The compound class shows excellent developability due to the modular
      synthesis, allowing independent optimization of all three to four key
      substituents to improve the properties of the molecules. 

PMID- 24139846
TI  - Cohort monitoring - as a tool to improve diabetes care services.
AB  - The need to stem the rising tide of non-communicable diseases (NCDs) including
      diabetes has been recognised at the highest levels through the UN political
      declaration. Diabetes care services are largely unavailable in the primary care
      setting in most developing countries and where available the services are
      unstructured, with poor record keeping, stock outs and frequent disruption in
      supplies. With no systematic monitoring of care and programme implementation,
      treatment outcomes are poor and are consequently associated with a high economic
      burden. Systematic evaluation of programmes through cohort monitoring has been
      shown to be effective in large-scale interventions for two chronic infectious
      diseases-tuberculosis and HIV/AIDS. Can the same simple tool of cohort monitoring
      be applied to improve diabetes care delivery in the developing world? Pilot
      projects show it is possible, but scale up and expansion would require investment
      in information technology. In a scenario where systems for NCD are just beginning
      to be set up, it makes sense to learn from and build further on the initial pilot
      programmes. 

PMID- 24139847
TI  - Long-term weight change in adulthood and incident diabetes mellitus: MY Health Up
      Study.
AB  - AIM: To investigate whether long-term weight/BMI change in adulthood has a
      significant impact on the incidence of diabetes, independent of attained weight
      status. METHODS: A number of 13,700 participants (2962 men and 10,738 women) aged
      36 to 55 years were followed for up to 5 years using data from annual health
      checkups. Incident cases of diabetes were identified from self-reports or single
      fasting plasma glucose measurements (>=7.0 mmol/l). Weight/BMI change was
      calculated from participants' weight/BMI values at age 20 years and weight/BMI
      values at a given point during follow-up and used as a time-dependent variable in
      age-stratified multivariate Cox proportional hazards models. RESULTS: During the
      5 year follow-up, 408 participants (137 men and 271 women) developed diabetes.
      Even after adjusting for BMI during follow-up and other possible confounders,
      weight/BMI gain since age 20 years was significantly associated with an increased
      risk of developing diabetes. The hazard ratios were: 2.30 (95% confidence
      interval (CI): 1.31-4.04) for those who gained 6.0 to <10.0 kg and 3.09 (95% CI:
      1.79-5.34) for those who gained >=10.0 kg [reference: <2.0 kg change]; and 2.61
      (95% CI: 1.58-4.31) for those who gained 3.0 to <5.0 kg/m(2) and 3.70 (95% CI:
      2.22-6.16) for those who gained >=5.0 kg/m(2) [reference: <1.0 kg/m(2) change].
      CONCLUSIONS: The results indicate that long-term weight/BMI gain in adulthood is
      a significant predictor for the development of diabetes, independent of attained
      weight status. Because weight gain within the normal weight range could increase
      the risk of diabetes, non-obese people should also be warned against possible
      weight gain.

PMID- 24139848
TI  - Microbial modulators of soil carbon storage: integrating genomic and metabolic
      knowledge for global prediction.
AB  - Soil organic carbon performs a number of functions in ecosystems and it is clear
      that microbial communities play important roles in land-atmosphere carbon (C)
      exchange and soil C storage. In this review, we discuss microbial modulators of
      soil C storage, 'omics'-based approaches to characterize microbial system
      interactions impacting terrestrial C sequestration, and how data related to
      microbial composition and activities can be incorporated into mechanistic and
      predictive models. We argue that although making direct linkage of genomes to
      global phenomena is a significant challenge, many connections at intermediate
      scales are viable with integrated application of new systems biology approaches
      and powerful analytical and modelling techniques. This integration could enhance
      our capability to develop and evaluate microbial strategies for capturing and
      sequestering atmospheric CO2. 

PMID- 24139849
TI  - Neuromuscular blocking activity of pinnatoxins E, F and G.
AB  - Pinnatoxins are produced by dinoflagellates and belong to the cyclic imine family
      of toxins. They are fast-acting and highly toxic when administered in vivo in
      rodent bioassays, causing death by respiratory depression within minutes. Studies
      have revealed that some cyclic imine toxins cause their toxicity by antagonizing
      both muscle type and heteromeric and homomeric neuronal nicotinic acetylcholine
      receptors (nAChRs). Pinnatoxins E, F and G all display potent toxicity in in vivo
      bioassays, with symptoms of toxicity similar to other cyclic imine toxins.
      However, very little work has been done on the mechanism of action of these
      pinnatoxin isomers. Thus the aim of the current study was to investigate the rank
      order of potency and mechanism of action of pinnatoxins E, F and G. The effects
      of pinnatoxin E, F and G on in vitro rat hemidiaphragm preparations were
      investigated using twitch tension and electrophysiological techniques to
      determine the effects of these toxins on cholinergic transmission at the
      neuromuscular junction. Pinnatoxins E, F and G all produced concentration
      dependent reductions in the nerve evoked twitch response of the rat
      hemidiaphragm, with IC50 values ranging from 11 to 53 nM and a rank order of
      potency of F > G > E. Only complete washout of pinnatoxin E was evident, with
      pinnatoxins F and G displaying slow and incomplete washout profiles. Pinnatoxins
      F and G also reduced the amplitudes of spontaneous miniature endplate potentials
      and evoked endplate potentials at the neuromuscular junction, without affecting
      miniature endplate potential frequency or the resting membrane potential of the
      muscle fibres. These results show that pinnatoxins E, F and G are all potent
      neuromuscular blocking agents and cause toxicity by acting as antagonists at
      muscle type nicotinic acetylcholine receptors. 

PMID- 24139850
TI  - Suppression of severe lesions, myonecrosis and hemorrhage, caused by
      Protobothrops flavoviridis venom with its serum proteins.
AB  - Protobothrops flavoviridis serum proteins precipitated with ammonium sulfate were
      chromatographed on a DEAE-Toyopearl 650M column at pH 7.5 with stepwise increase
      or with linear gradient of NaCl concentration. Peaks 3 and 4 serum proteins,
      obtained by linear gradient elution and named Fr(de3) and Fr(de4), contained Habu
      serum factors (HSF) and phospholipase A2 (PLA2) inhibitors (PfPLI), respectively.
      The serum proteins eluted at 0.2 M NaCl by stepwise elution, named Fr(0.2NaCl),
      effectively suppressed myonecrosis and hemorrhage caused by P. flavoviridis venom
      in rat or mouse thigh muscles. The Fr(0.2NaCl) were fractionated by HPLC and the
      fractions, after SDS-PAGE, underwent far-western blot analysis with PLA2
      ([Asp(49)]PLA2) and BPI ([Lys(49)]PLA2) as the probes. Four PfPLIs, namely,
      PfalphaPLI-A, PfalphaPLI-B, PfgammaPLI-A and PfgammaPLI-B, were identified
      together with their selective binding specificities to PLA2 species. In addition,
      a new 9 kDa protein, which is specifically bound to BPI, was found. Suppression
      of P. flavoviridis venom-induced severe lesions, such as myonecrosis, hemorrhage
      and edema, with its serum proteins was histopathologically observed in the
      present work for the first time. The cooperative use of P. flavoviridis antivenom
      and its serum proteins as medication for P. flavoviridis snake bites is
      discussed.

PMID- 24139851
TI  - Food-independent tendency to disadvantageous decisions in obese individuals with
      regular binge eating.
AB  - OBJECTIVE: The objective of this study was to explore whether or not obese
      patients with and without regular binge eating differ with regard to their
      decision-making abilities. METHODS: Decision-making was measured by using a
      computerized version of the Iowa Gambling task (IGT) in 34 obese patients with
      regular binge eating (BE(+)) and 34 obese individuals without binge eating (BE(
      )) matched for age and sex. In addition, computerized versions of the Auditory
      Verbal Learning Test and the Corsi Block Tapping Test were administered.
      Participants further answered questionnaires concerning eating disorder symptoms
      (Eating Disorder Examination-Questionnaire) and depression (Patient Health
      Questionnaire depression scale). RESULTS: The BE(+) group reported more eating
      disorder and depressive symptoms than the BE(-) group but did not differ with
      regard to BMI, working memory deficits, depressive symptoms, somatic comorbidity
      (i.e., hypertension, diabetes, sleep apnea, hyperlipidemia, pain disorder), or
      education. Binge eating participants showed poorer decision-making abilities
      based on the total IGT net scores. However, they did not differ from those
      without regular binge eating in improving their choice behavior over the task.
      CONCLUSIONS: The group difference in total IGT net scores suggests more general,
      food-independent decision making problems in obese individuals with regular binge
      eating compared to those without. Treatment of obese patients with BED could be
      enhanced by training them to better control risky decisions, to delay
      gratification in an effortful way and to activate appropriate alternative
      behaviors.

PMID- 24139852
TI  - Interpersonal problem areas and alexithymia in adolescent girls with loss of
      control eating.
AB  - This study investigated the links among interpersonal problem areas, depression,
      and alexithymia in adolescent girls at high risk for excessive weight gain and
      binge eating disorder. Participants were 56 girls (Mage = 14.30, SD = 1.56; 53%
      non-Hispanic White) with a body mass index (BMI, kg/m(2)) between the 75th and
      97th percentiles (MBMI z = 1.57, SD = 0.32). By design, all participants reported
      loss of control eating patterns in the past month. Adolescents were individually
      interviewed prior to participating in a group interpersonal psychotherapy obesity
      and eating disorder prevention program, termed IPT for the prevention of
      excessive weight gain (IPT-WG). Participants' interpersonal problem areas were
      coded by trained raters. Participants also completed questionnaires assessing
      depression and alexithymia. Primary interpersonal problem areas were categorized
      as interpersonal deficits [as defined in the eating disorders (ED) literature] (n
      = 29), role disputes (n = 22), or role transitions (n = 5). Girls with
      interpersonal deficits-ED had greater depressive symptoms and alexithymia than
      girls with role disputes (p's <= 0.01). However, girls with role transitions did
      not differ from girls with interpersonal deficits-ED or role disputes.
      Interpersonal problem area had an indirect association with depression via
      alexithymia; interpersonal deficits-ED were related to greater alexithymia, which
      in turn, was related to greater depressive symptoms (p = 0.01). Among girls at
      risk for excess weight gain and eating disorders, those with interpersonal
      deficits-ED appear to have greater distress as compared to girls with role
      disputes or role transitions. Future research is required to elucidate the impact
      of interpersonal problem areas on psychotherapy outcomes.

PMID- 24139853
TI  - Waist circumference and not body mass index as the outcome of a group weight
      intervention for patients with severe mental illness.
AB  - OBJECTIVE: Most weight interventions among patients with severe mental illness
      (SMI) used body mass index (BMI) as outcome measure but excluded waist
      circumference (WC) although the latter is a stronger predictor of obesity
      complications. This study aimed to assess a weight-management program consisting
      of education, exercise and behavioural techniques for patients with SMI using
      weight parameters including WC as the outcome measures. METHODS: A group
      intervention was carried out as part of psychiatric outpatient community service.
      It used structured modules on diet, exercise and related topics comprising of
      education and exercises sessions with a total of 12-week duration. The
      participants were outpatients with SMI recruited through referrals to the program
      by the treating doctor. The participants' body weight, BMI and WC were measured
      at the baseline, fortnightly and at the end of the program. RESULTS: A total of
      27 patients participated in the program which was carried out in 6 cycles. The
      pre- and post-intervention comparisons analysis of the weight parameters found a
      significant reduction in the WC (mean=3.878 cm+5.165, p=0.001) while no
      significant changes were recorded in body weight and BMI. CONCLUSION: Small but
      significant loss in WC and possibly weight maintenance were achieved using this
      non-pharmacological intervention. Modest loss in WC may have an impact on
      reducing the risk of obesity-related health risks.

PMID- 24139854
TI  - Minocycline exerts acute inhibitory effects on cerebral cortex excitability in
      humans.
AB  - Minocycline has efficacy to alleviate seizure activity in animal models of
      epilepsy. Among other mechanisms it has been postulated that minocycline can
      inhibit microglial activation and develop beneficial effects by decreasing
      glutamate excitotoxicity. To explore acute effects of minocycline on human motor
      cortex excitability we used single- and paired-pulse transcranial magnetic
      stimulation in 12 healthy subjects 4h after a single oral dose of 200mg
      minocycline or placebo was administered in a randomised, double-blind, placebo
      controlled crossover design. Mean cortical silent period, an inhibitory parameter
      of predominantly intracortical origin, was prolonged after minocycline compared
      to placebo, while other TMS parameters of cortical excitability remained
      unchanged. The results demonstrate that a particular parameter of cortical
      inhibition is rapidly increased after a single oral dose of minocycline in
      humans. 

PMID- 24139855
TI  - Modulation of excitability by continuous low- and high-frequency stimulation in
      fully hippocampal kindled rats.
AB  - BACKGROUND: Low- and high-frequency stimulation (LFS and HFS, respectively) have
      been, reported to modify seizure characteristics in rats. We here report effects
      of hippocampal LFS and HFS, applied at two or four sites in fully kindled rats.
      METHODS: Rats were kindled through a hippocampal tetrode until the fully kindled
      state. Animals with, stable afterdischarge (AD) threshold were randomly assigned
      to 5 groups; stimulation at 1Hz (LFS) or, 130Hz (HFS) was continuously applied
      for 7 days at 2 or 4 intrahippocampal sites; a control, group received no
      stimulation. Four-contact stimulation was performed in a rotating fashion.
      Stimulation effects on AD threshold, AD duration and behavioral seizures were
      assessed. KEY FINDINGS: Four-contact LFS consistently increased AD threshold for
      a period of 2 days to 2 weeks, whereas 4-contact HFS significantly decreased AD
      duration 24hours following the stimulation period. No significant AD modification
      was observed with either 2-contact stimulation paradigms. No, behavioral
      alteration occurred in any group. SIGNIFICANCE: These findings suggest that
      effects of hippocampal stimulation depend on frequency and topography of stimulus
      application. LFS and HFS had anti-epileptic effect on afterdischarges when
      applied in a rotating pattern. This supports concepts on patterned stimulation to
      result in desynchronization and anti-kindling effects.

PMID- 24139857
TI  - A haploinsufficiency of FOXG1 identified in a boy with congenital variant of Rett
      syndrome.
AB  - BACKGROUND: Forkhead box G1 gene (FOXG1) mutations and deletions are associated
      with a congenital variant of Rett syndrome (RTT). Nucleotide alterations of the
      coding region of FOXG1 have never caused dysmorphic features. PATIENT: An 8-year
      old boy with the congenital variant of RTT who showed severe psychomotor
      deterioration, epilepsy, acquired microcephaly, and involuntary movements
      including jerky movements of the upper limbs and tongue protrusion. He showed
      dysmorphic features including round face, anteverted nostrils, and tented upper
      lips. Brain magnetic resonance imaging showed hypoplasia of the frontal lobes and
      the rostral part of the corpus callosum. The molecular cytogenetic analysis
      confirmed a de novo deletion of 14q12 including FOXG1 in this patient.
      CONCLUSION: We identified the smallest deletion of 14q12 involving FOXG1 among
      those previously reported. Dysmorphic facial features are a characteristic for
      the patients with chromosomal deletion including FOXG1. In our patient, C14orf23
      is the only transcript other than FOXG1. Therefore, C14orf23 might be responsible
      for facial dysmorphism.

PMID- 24139856
TI  - Racial and ethnic differences in epilepsy classification among probands in the
      Epilepsy Phenome/Genome Project (EPGP).
AB  - Little is known about the ethnic and racial differences in the prevalence of
      generalized and focal epilepsy among patients with non-acquired epilepsies. In
      this study, we examined epilepsy classification and race/ethnicity in 813
      probands from sibling or parent-child pairs with epilepsy enrolled in the
      Epilepsy Genome/Phenome Project (EPGP). Subjects were classified as generalized
      epilepsy (GE), non-acquired focal epilepsy (NAFE), mixed epilepsy syndrome (both
      generalized and focal), and unclassifiable, based on consensus review of
      semiology and available clinical, electrophysiology, and neuroimaging data. In
      this cohort, 628 (77.2%) subjects identified exclusively as Caucasian/white and
      65 (8.0%) subjects reported African ancestry, including subjects of mixed-race.
      Of the Caucasian/white subjects, 357 (56.8%) had GE, 207 (33.0%) had NAFE, 32
      (5.1%) had a mixed syndrome, and 32 (5.1%) were unclassifiable. Among subjects of
      African ancestry, 28 (43.1%) had GE, 27 (41.5%) had NAFE, 2 (3.1%) had a mixed
      syndrome, and 8 (12.3%) were unclassifiable. There was a higher proportion of
      subjects with GE compared to other syndromes among Caucasians/whites compared to
      subjects with African ancestry (OR 1.74, 95% CI: 1.04-2.92, two-tailed Fisher's
      exact test, p=0.036). There was no difference in the rate of GE among subjects
      reporting Hispanic ethnicity (7.6% of total) when adjusted for race
      (Caucasian/white vs non-Caucasian/white; OR 0.65, 95% CI: 0.40-1.06, p>0.05). The
      proportion of participants with unclassifiable epilepsy was significantly greater
      in those of African-American descent. In a group of patients with epilepsy of
      unknown etiology and an affected first degree relative, GE is more common among
      Caucasian/white subjects than among those with African ancestry. These findings
      suggest there may be geographical differences in the distribution of epilepsy
      susceptibility genes and an effect of genetic background on epilepsy phenotype.
      However, the results should be interpreted with caution because of the low
      numbers of African-Americans in this cohort and more limited diagnostic data
      available for epilepsy classification in these subjects compared to
      Caucasians/whites. 

PMID- 24139858
TI  - Pseudotumor cerebri/idiopathic intracranial hypertension in children: an
      experience of a tertiary care hospital.
AB  - OBJECTIVE: Pseudotumor cerebri (PTC) is diagnosed at increasing rates probably
      due to the increase in obesity prevalence all over the world and awareness about
      the disease. Our aim in this study was to evaluate the PTC clinical picture and
      etiological factors in children at the present time. METHOD: The records of 53
      patients with 32 females, who were diagnosed with PTC in a child neurology
      department between the years of 2005 and 2012 were retrospectively analyzed.
      RESULTS: The mean age at presentation was 10.9 years (3-17 years) and
      approximately half of patients were aged of 11 years or less. While more than
      half of prepubertal patients were male, girls rate reaches 74% at puberty. An
      etiological factor such as venous sinus thrombosis, infections, anemia, steroid
      discontinuation, drugs, slit ventricle syndrome and minor head injury causing the
      PTC was identified in 43% of the patients. The mean duration of treatment was 6.4
      months (3-24 months) and the mean follow-up duration 16.5 months (3-52 months).
      Visual field constriction was moderate in only two pubertal and obese female
      patients and mild in four patients. CONCLUSIONS: PTC is seen in prepubertal
      children as often as in puberty. An etiological factor causing PTC is present in
      about half the patients in childhood. The main etiological factors of the disease
      currently consist of cranial venous thrombosis, infections, anemia and drugs.
      Malnutrition, renutrition and related vitamin deficiencies or excesses commonly
      seen previously have become less important in PTC etiology. PTC is a disease that
      requires long-term treatment and follow-up but the prognosis is good in patients
      who are diagnosed early, receive appropriate treatment and show good compliance
      with the treatment.

PMID- 24139859
TI  - Semaphorin 3E suppresses tumor cell death triggered by the plexin D1 dependence
      receptor in metastatic breast cancers.
AB  - The semaphorin guidance molecules and their receptors, the plexins, are often
      inappropriately expressed in cancers. However, the signaling processes mediated
      by plexins in tumor cells are still poorly understood. Here, we demonstrate that
      the Semaphorin 3E (Sema3E) regulates tumor cell survival by suppressing an
      apoptotic pathway triggered by the Plexin D1 dependence receptor. In mouse models
      of breast cancer, a ligand trap that sequesters Sema3E inhibited tumor growth and
      reduced metastasis through a selective tumor cytocidal effect. We further showed
      that Plexin D1 triggers apoptosis via interaction with the orphan nuclear
      receptor NR4A1. These results define a critical role of Sema3E/Plexin D1
      interaction in tumor resistance to apoptosis and suggest a therapeutic approach
      based on activation of a dependence receptor pathway. 

PMID- 24139860
TI  - Chewing thoroughly reduces eating rate and postprandial food palatability but
      does not influence meal size in older adults.
AB  - Recent studies have shown that increasing the number of chews before swallowing
      reduces meal size in young adults. However, whether this ingestive behavior
      influences meal size in older adults is unknown. Eighteen older adults (4 males
      and 14 females, age 72+/-1years, body mass index 25.9+/-1.2kg/m(2)) participated
      in this randomized cross-over trial. A preliminary session was conducted to
      assess their habitual number of chews (HNC) using pizza rolls as the test food.
      Participants then attended three test sessions at their habitual lunch time. In
      each test session, participants were asked to eat pizza rolls until comfortably
      full, by chewing each pizza roll for 100%, 150% and 200% of HNC before
      swallowing. Subjective appetite was measured at regular time points for 60min
      after meal initiation. There was no difference in meal duration and meal induced
      change in appetite at meal termination between test sessions. However, eating
      rate at the 150% and 200% of HNC sessions (16.4+/-1.0g/s and 13.7+/-0.8g/s,
      respectively) was significantly reduced, compared with eating rate at the 100% of
      HNC condition (22.5+/-1.8g/s). Moreover, thorough chewing significantly reduced
      postprandial ratings on palatability of the test food. There was no significant
      difference in food intake between test sessions (177.8+/-43.0g, 164.0+/-41.7g,
      and 166.6+/-33.0g for 100%, 150% and 200% of HNC, respectively). These results
      suggest that increasing the number of chews does not affect meal size in older
      adults. Aging-related appetite dysregulation may partly account for the
      difference in results from studies in young and older adults. 

PMID- 24139861
TI  - 2'-Hydroxy ceramide in membrane homeostasis and cell signaling.
AB  - Ceramide is a precursor of complex sphingolipids and also plays important roles
      in cell signaling. With the advances in lipid analytical technologies, the
      structural diversity of ceramide species have become evident, and the complexity
      of cellular metabolism and function associated with distinct ceramide species is
      beginning to be revealed. One of the common structural variations of ceramide is
      2'-hydroxylation of the N-acyl chain. Fatty acid 2-hydroxylase (FA2H) is one of
      the enzymes that introduce the hydroxyl group during de novo synthesis of
      ceramide. FA2H is essential for the normal functioning of the nervous system, as
      evidenced by demyelinating disorder associated with FA2H mutations in humans and
      mice. Studies of Fa2h mutant mice indicate that lack of 2'-hydroxy
      galactosylceramide in the myelin membrane results in loss of long-term stability
      of myelin and eventual demyelination. FA2H also regulates differentiation of
      various cell types (epidermal keratinocytes, schwannoma cells, adipocytes). When
      provided exogenously, ceramide induces apoptosis in many cell types.
      Interestingly, the effective concentration of 2'-hydroxy ceramide that induces
      apoptosis is significantly lower compared to non-hydroxy ceramide, and cells die
      much more rapidly, suggesting that 2'-hydroxy ceramide can mediate proapoptotic
      signaling distinct from non-hydroxy ceramide. Collectively, current evidence
      clearly shows that 2'-hydroxy ceramide and 2'-hydroxy complex sphingolipids have
      unique functions in membrane homeostasis and cell signaling that could not be
      substituted by non-hydroxy counterparts. 

PMID- 24139862
TI  - Quantitative estimation of the high-intensity zone in the lumbar spine:
      comparison between the symptomatic and asymptomatic population.
AB  - BACKGROUND CONTEXT: The high-intensity zone (HIZ) on magnetic resonance imaging
      (MRI) has been studied for more than 20 years, but its diagnostic value in low
      back pain (LBP) is limited by the high incidence in asymptomatic subjects. Little
      effort has been made to improve the objective assessment of HIZ. PURPOSE: To
      develop quantitative measurements for HIZ and estimate intra- and interobserver
      reliability and to clarify different signal intensity of HIZ in patients with or
      without LBP. STUDY DESIGN: A measurement reliability and prospective comparative
      study. PATIENT SAMPLE: A consecutive series of patients with LBP between June
      2010 and May 2011 (group A) and a successive series of asymptomatic controls
      during the same period (group B). OUTCOME MEASURES: Incidence of HIZ;
      quantitative measures, including area of disc, area and signal intensity of HIZ,
      and magnetic resonance imaging index; and intraclass correlation coefficients
      (ICCs) for intra- and interobserver reliability. METHODS: On the basis of HIZ
      criteria, a series of quantitative dimension and signal intensity measures was
      developed for assessing HIZ. Two experienced spine surgeons traced the region of
      interest twice within 4 weeks for assessment of the intra- and interobserver
      reliability. The quantitative variables were compared between groups A and B.
      RESULTS: There were 72 patients with LBP and 79 asymptomatic controls enrolling
      in this study. The prevalence of HIZ in group A and group B was 45.8% and 20.2%,
      respectively. The intraobserver agreement was excellent for the quantitative
      measures (ICC=0.838-0.977) as well as interobserver reliability (ICC=0.809
      0.935). The mean signal of HIZ in group A was significantly brighter than in
      group B (57.55+/-14.04% vs. 45.61+/-7.22%, p=.000). There was no statistical
      difference of area of disc and HIZ between the two groups. The magnetic resonance
      imaging index was found to be higher in group A when compared with group B
      (3.94+/-1.71 vs. 3.06+/-1.50), but with a p value of .050. CONCLUSIONS: A series
      of quantitative measurements for HIZ was established and demonstrated excellent
      intra- and interobserver reliability. The signal intensity of HIZ was different
      in patients with or without LBP, and significant brighter signal was observed in
      symptomatic subjects.

PMID- 24139863
TI  - Early versus late surgery of thoracic spine fractures in multiple injured
      patients: is early stabilization always recommendable?
AB  - BACKGROUND CONTEXT: Many institutions' retrospective studies investigated the
      effect of the timing of surgery on outcomes of polytraumatized patients with
      severe lesions of the thoracic spine and mainly found a better outcome for
      patients who were operated on less than 72 hours posttrauma. PURPOSE: We
      conducted a prospective study in a Level I trauma center to validate the
      retrospective data and to investigate other variables, in addition to the timing
      of surgery that may influence patient outcomes. STUDY DESIGN: Prospective
      observational clinical study. PATIENT SAMPLE: Within this prospective study at a
      Level I trauma center, we enrolled 38 multiple injured patients with unstable
      fractures of vertebral column from Level Th1 to L1. Further inclusion criteria
      consisted of an injury severity score of 16 or more and an intensive care unit
      (ICU) stay of more than 7 days. The age of included patients was limited from 16
      or more to 75 or less years. OUTCOME MEASURES: Hospital stay, stay on ICU, and
      mortality. METHODS: Twenty-two patients were operated on less than or equal to 72
      hours posttrauma, and 16 received late surgery greater than or equal to 72 hours
      posttrauma. RESULTS: Patients who received early surgery had a significantly
      higher mortality rate (p<.01) than those who received late surgery. Sixty-seven
      percent of our patients who had an initial hemoglobin (Hb) less than 10 mg/dL
      died. Seventy-five percent of those patients who had an Hb less than 10 mg/dL and
      received a thoracic drain died. CONCLUSIONS: Although some reports indicate
      advantages for early surgery for thoracic spine trauma in the polytraumatized
      patient, careful patient selection should be used. Based on the results of this
      prospective study, early surgery for thoracic spine trauma in patients with
      concomitant severe thoracic trauma and low initial Hb levels may pose a risk for
      poor clinical outcomes.

PMID- 24139864
TI  - The effect of application site of spinal manipulative therapy (SMT) on spinal
      stiffness.
AB  - BACKGROUND CONTEXT: Like other factors that can influence treatment efficacy (eg,
      dosage, frequency, time of day), the site of treatment application is known to
      affect various physical interventions such as topical anesthetics and
      cardiopulmonary resuscitation. Like these examples, spinal manipulative therapy
      (SMT) is a physical intervention that may exhibit maximal benefit when directed
      to a specific site. Whereas numerous studies of SMT efficacy have produced mixed
      results, few studies have taken into account the site of SMT application.
      PURPOSE: To determine if the site of SMT application modulates the effect of SMT
      in an anesthetized feline model. STUDY DESIGN: Spinal manipulative therapy
      applied to specific anatomic locations randomized in a Latin square design with a
      no-SMT control. OUTCOME MEASURES: Physiologic measures (spinal stiffness).
      METHODS: Simulated SMT was delivered by a validated mechanical apparatus to the
      intact lumbar spine of eight anesthetized felines at four unique sites: L6
      spinous process, left L6 lamina, left L6 mammillary process, and L7 spinous
      process. To measure spinal stiffness, a separate indentation load was applied
      mechanically to the L6 spinous process before and after each SMT application.
      Spinal stiffness was calculated from the resulting force-displacement curve as
      the average stiffness (k) and terminal instantaneous stiffness (TIS). RESULTS:
      Relative to the no-SMT control, significant decreases in spinal stiffness
      followed the SMT when L6 spinous and L6 lamina were used as the contact site.
      Terminal instantaneous stiffness significantly decreased -0.48 N/mm (upper, lower
      95% confidence interval [-0.86, -0.09]) with L6 spinous as the contact site and
      decreased -0.44 N/mm (-0.82, -0.05), with the L6 lamina as the contact site. k
      increased 0.44 N/mm (-0.01, 088), using L6 spinous as the contact site.
      CONCLUSIONS: Decreases in terminal spinal stiffness were observed after SMT
      delivered at some application sites but not the others. The results suggest that
      SMT contact site modulates SMT's effect on spinal stiffness in a feline model.
      Changes in spinal terminal instantaneous spinal stiffness were similar in
      magnitude and direction to those observed in symptomatic human subjects who
      report benefits after SMT.

PMID- 24139865
TI  - Bone biomarkers in patients with chronic traumatic spinal cord injury.
AB  - BACKGROUND CONTEXT: Bone loss after spinal cord injury (SCI) occurs because of
      pathologic changes in osteoblastic and osteoclastic activities due to mechanical
      unloading. Some biochemical changes in bone metabolism after SCI are described
      before that were related to bone mineral loss. PURPOSE: Our purpose was to
      determine bone markers' changes and related effective factors in patients with
      chronic traumatic SCI. STUDY DESIGN: This investigation was designed as an
      observational cross-sectional study. PATIENT SAMPLE: All patients with chronic
      SCI who were referred to Brain and Spinal Injury Research Center and did not meet
      our exclusion criteria entered the study. OUTCOME MEASURES: Self-reporting
      measures including patient's demographic features and date of accident were
      obtained using a questionnaire and physiologic measures including spinal magnetic
      resonance imaging to determine the level of injury accompanied with physical
      examination along with dual-energy X-ray absorptiometry were performed. Blood
      samples were analyzed in the laboratory. METHODS: Dual-energy X-ray was used to
      determine bone mineral density in femoral and spinal vertebrae bone sites. Serum
      level of C-telopeptide cross-linked Type 1 collagen (CTX), parathyroid hormone,
      calcitonin, osteocalcin, and bone alkaline phosphatase (BALP) were measured.
      RESULTS: We detected a negative association between CTX level and bone mineral
      density in femoral and spinal bone sites that confirms that CTX is a bone
      resorption marker. C-telopeptide cross-linked Type 1 collagen and BALP levels did
      not show any significant correlation with postduration injury. Patients with
      spinal injury at lumbar level had the highest calcitonin level (p<.04). C
      telopeptide cross-linked Type 1 collagen was positively related with osteocalcin
      and BALP (p<.0001, r=0.51), and osteocalcin was positively related with BALP
      (p<.0001, r=0.44). Osteocalcin was related negatively only to femoral
      intertrochanteric zone bone mineral density. CONCLUSIONS: Some bone biomarkers
      undergo noticeable changes after SCI. C-telopeptide cross-linked Type 1 collagen
      was positively correlated with BALP and osteocalcin that shows the coincidental
      occurrence of osteoblastic and osteoclastic activities. Our data also support
      this fact that although bone reduction after 2 years is slower than acute phase
      after SCI, bone resorption rate is higher than bone formation. These bone markers
      also revealed different site of action as osteocalcin level only affected femoral
      intertrochanteric bone mineral density. Generally, it seems that the coincidental
      consideration of these factors that influence bone mineral density can lead to a
      better understanding of bone changes after SCI.

PMID- 24139866
TI  - The molecular composition of the extracellular matrix of the human iliolumbar
      ligament.
AB  - BACKGROUND CONTEXT: The human iliolumbar ligament connects the transverse process
      of L5 to the iliac crest and contributes to lumbosacral stability and has been
      associated with low back pain. However, different opinions exist regarding the
      functional relevance of the ligament. PURPOSE: In the present study, we analyze
      the regional molecular composition of the ligament extracellular matrix. STUDY
      DESIGN: Special attention is given to the attachment sites, to determine whether
      the ligament is subjected to a certain mechanical environment. METHODS:
      Iliolumbar ligament samples, extending from one enthesis to the other, were
      removed from 11 cadavers and fixed in methanol. Cryosections were immunolabeled
      with a panel of antibodies directed against collagens, glycosaminoglycans,
      proteoglycans, matrix proteins, and neurofilament. RESULTS: The mid-substance of
      the ligament labeled for all the molecules normally found in dense fibrous
      connective tissue including types I, III, and VI collagen, versican, dermatan -,
      chondroitin 4 -, and keratan sulfate. However, both entheses were
      fibrocartilaginous and labeled for type II collagen, aggrecan, and chondroitin 6-
      sulfate. A common feature was fat between the fiber bundles near the entheses.
      Occasionally this fat contained nerve fibers. CONCLUSIONS: The existence of
      fibrocartilaginous entheses suggests that the insertion sites of the ligament are
      subject to both tensile and compressive loading-probably because of insertional
      angle changes between ligament and bone during loading. Our findings support the
      suggestion that the iliolumbar ligament might play an important role in the
      stabilization of the lumbosacral junction.

PMID- 24139867
TI  - Vertebroplasty and kyphoplasty: national outcomes and trends in utilization from
      2005 through 2010.
AB  - BACKGROUND CONTEXT: Vertebral compression fractures secondary to low bone mass
      are responsible for almost 130,000 inpatient admissions and 133,500 emergency
      department visits annually, totaling over $5 billion of direct inpatient costs.
      Although most vertebral compression fractures heal within a few months with
      conservative therapy, a significant portion fail to improve with conservative
      treatment and require long-term care, conservative treatment, or both. Fractures
      that fail conservative therapy are treated with vertebral augmentation procedures
      (VAPs) such as vertebroplasty (VP) and kyphoplasty (KP). Two large randomized
      clinical trials published in 2009 questioned the efficacy of VP in treatment of
      VAPs. PURPOSE: This study aimed to investigate trends in utilization of VP and KP
      between 2005 and 2010 to capture the impact of the 2009 literature on utilization
      of VAPs. The study also compares patient characteristics and perioperative
      outcomes between VP and KP to further delineate the risks of each procedure.
      STUDY DESIGN: Retrospective analysis of national utilization rates, clinical
      outcomes, patient demographics, and patient comorbidities using a large national
      inpatient database. PATIENT SAMPLE: A total of 63,459 inpatient admissions from
      46 states and more than 1,000 different hospitals were included in the analysis.
      OUTCOME MEASURES: Length of stay (LOS), total direct cost, mortality,
      postoperative complications. METHODS: Data were obtained from the National
      Inpatient Sample database for the period between 2005 and 2010. National
      Inpatient Sample is the largest publicly available all payer inpatient database
      in the United States. Patients undergoing VP and KP were identified via
      corresponding the International Classification of Diseases, 9th Revision
      procedure codes. National utilization trends were estimated using weights
      supplied as part of the National Inpatient Sample dataset. Information on patient
      comorbidities and demographics was collected. A series of univariate and
      multivarariate analyses were used to identify statistically significant
      differences in patient characteristics, clinical outcomes, as well as cost and
      LOS between patients undergoing VP versus KP. RESULTS: A total of 307,050
      inpatient VAPs were performed in the United States between 2005 and 2010. Of
      those procedures, 225,259 were KP and 81,790 were VP. Kyphoplasty utilization
      showed an increasing trend between 2005 and 2007, increasing from 27 to 33
      procedures per 100,000 capita older than 40 years. During the same time period,
      VP utilization remained constant at approximately nine procedures per 100,000
      capita older than 40 years. After 2007, utilization of both VP and KP decreased.
      The most precipitous decrease in VAP utilization occurred in 2009. Patients
      undergoing VP were on average older (76.7 vs. 77.8, p<.0001), more frequently
      women (74.48% vs. 73.15%, p=.00083), and black (1.77% vs. 1.55%, p=.004059).
      Patients undergoing VP had on average more comorbidities then those undergoing
      KP. Patients undergoing VP had a higher rate of postoperative anemia secondary to
      acute bleeding and higher rate of venous thromboembolic events. Those undergoing
      KP had a greater rate of cardiac complications; however, this difference was not
      statistically significant when taking into account patient age and comorbidity
      burden. Vertebroplasty was associated with higher mortality (0.93% vs. 0.60%,
      p<.001), longer LOS (6.78 vs. 5.05 days, p<.0001), and lower total cost ($42,154
      vs. $46,101, p<.0001). CONCLUSIONS: Overall, KP was associated with lower
      complication rates, shorter LOS, and a higher total direct cost compared with VP.
      Utilization rates showed a significant decrease since 2009 in both VP and KP,
      suggesting that both procedures were impacted by the two randomized controlled
      trials published in 2009 that suggested poor efficacy of VP.

PMID- 24139868
TI  - Caloric vestibular stimulation modulates affective control and mood.
AB  - BACKGROUND: Clinical evidence suggests a link between vestibular dysfunctions and
      mood disorders. No study has yet investigated mood and affective control during
      vestibular stimulation in healthy participants. OBJECTIVE: We predicted a
      modulating effect of caloric vestibular stimulation (CVS) on affective control
      measured in an affective Go/NoGo task (AGN). METHODS: Thirty-two participants
      performed an AGN task while they were exposed to cold left or right ear CVS (20 
      degrees C) and sham stimulation (37  degrees C). In each block, either positive
      or negative pictures (taken from the International Affective Picture System) were
      defined as targets. Participants had to respond to targets (Go), and withhold
      responses to distractors (NoGo). RESULTS: The sensitivity index d' (hits - false
      alarms) was used to measure affective control. Affective control improved during
      right ear CVS when viewing positive stimuli (P = .005), but decreased during left
      ear CVS when compared to sham stimulation (P = .009). CVS had a similar effect on
      positive mood ratings (Positive and Negative Affect Schedule). Positive mood
      ratings decreased during left ear CVS when compared to sham stimulation, but
      there was no effect after right ear CVS. DISCUSSION: The results suggest that
      CVS, depending on side of stimulation, has a modulating effect on mood and
      affective control. The results complement previous findings in manic patients and
      provide new evidence for the clinical potential of CVS.

PMID- 24139869
TI  - Characterization of predictors of in-hospital cardiac complications of takotsubo
      cardiomyopathy: multi-center registry from Tokyo CCU Network.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TC) is an acute cardiac syndrome
      characterized by transient left ventricular dysfunction and relatively good
      prognosis after discharge. However, cardiac complications during hospitalization
      remain to be fully determined. We attempted to determine features characterizing
      patients with adverse clinical outcome by comparing those with cardiac
      complication and without cardiac complication during hospitalization. METHODS AND
      RESULTS: We investigated 107 patients with TC from the Tokyo CCU Network
      database, comprising 67 cardiovascular centers in the metropolitan area during
      January 1 to December 31, 2010. Cardiac complications were defined as cardiac
      death, pump failure (Killip grade>=II), sustained ventricular tachycardia or
      fibrillation (SVT/VF), and advanced atrioventricular block (AVB). Cardiac
      complications were observed in 41 patients (37 pump failure complicated by 3
      cardiac deaths and 2 SVT/VF and 2 AVB without pump failure), and there was no
      cardiac complication in the remaining 66 patients. There was no difference in
      age, peak creatinine kinase level, C-reactive protein level and ST elevation on
      electrocardiogram. Multiple logistic regression analysis showed that white blood
      cell count (p=0.039) and brain natriuretic peptide (p=0.001) were independent
      predictors of in-hospital adverse cardiac complications. CONCLUSIONS: Cardiac
      complications are relatively high in patients with TC during hospitalization.
      High white blood cell count and brain natriuretic peptide level are associated
      with poor clinical outcome in patients with TC.

PMID- 24139870
TI  - Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status.
AB  - Hyperoxia exposure can inhibit alveolar growth in the neonatal lung through
      induction of p21/p53 pathways and is a risk factor for the development of
      bronchopulmonary dysplasia (BPD) in preterm infants. We previously found that
      activation of nuclear factor erythroid 2 p45-related factor (Nrf2) improved
      survival in neonatal mice exposed to hyperoxia likely due to increased expression
      of anti-oxidant response genes. It is not known however, whether hyperoxic
      induced Nrf2 activation attenuates the growth impairment caused by hyperoxia in
      neonatal lung. To determine if Nrf2 activation modulates cell cycle regulatory
      pathway genes associated with growth arrest we examined the gene expression in
      the lungs of Nrf2(-/-) and Nrf2(+/+) neonatal mice at one and 3days of hyperoxia
      exposure. METHODS: Microarray analysis was performed in neonatal Nrf2(+/+) and
      Nrf2(-/-) lungs exposed to one and 3days of hyperoxia. Sulforaphane, an inducer
      of Nrf2 was given to timed pregnant mice to determine if in utero exposure
      attenuated p21 and IL-6 gene expression in wildtype neonatal mice exposed to
      hyperoxia. RESULTS: Cell cycle regulatory genes were induced in Nrf2(-/-) lung at
      1day of hyperoxia. At 3days of hyperoxia, induction of cell cycle regulatory
      genes was similar in Nrf2(+/+) and Nrf2(-/-) lungs, despite higher inflammatory
      gene expression in Nrf2(-/-) lung. CONCLUSION: p21/p53 pathways gene expression
      was not attenuated by Nrf2 activation in neonatal lung. In utero SUL did not
      attenuate p21 expression in wildtype neonatal lung exposed to hyperoxia. These
      findings suggest that although Nrf2 activation induces expression of anti-oxidant
      genes, it does not attenuate alveolar growth arrest caused by exposure to
      hyperoxia.

PMID- 24139871
TI  - Role of IL6, IL12B and VDR gene polymorphisms in Plasmodium vivax malaria
      severity, parasitemia and gametocytemia levels in an Amazonian Brazilian
      population.
AB  - OBJECTIVE: To investigate the influence of IL6, IL12B and VDR single nucleotide
      polymorphisms (SNPs) in uncomplicated Plasmodium vivax infection symptoms
      intensity, parasitemia and gametocytemia levels in a Brazilian Amazonian
      population. METHODS: A total of 167 malaria patients infected by P. vivax have
      parasitemia and gametocytemia levels estimated before treatment. Fourteen
      clinical symptoms were evaluated and included in a principal component analysis
      to derive a clinical symptom index. Patients were genotyped for IL6-174C>G, IL12B
      735T>C, 458A>G, 159A>C, and VDR FokI, TaqI, BsmI SNPs by Taqman 5' nuclease
      assays. A General Linear Model analysis of covariance with age, gender, exposure
      period and infection history and genetic ancestry was performed to investigate
      the association of genotypes with parasitemia and gametocytemia levels and with a
      clinical symptom index. RESULTS: Higher parasitemia levels were observed in IL6
      174C carriers (p=0.02) whereas IL12B CGT haplotype carriers presented lower
      parasitemia levels (p=0.008). VDR TaqIC/BsmIA haplotype carriers showed higher
      gametocyte levels than non-carriers (p=0.013). Based on the clinical index values
      the IL6-174C>G polymorphism was associated with malaria severity. The IL6-174C
      carriers presented a more severe clinical index when compared to GG homozygotes
      (p=0.001). CONCLUSION: The present study suggests that IL6, IL12 and VDR
      influence severity, parasitemia and gametocytemia clearance in P. vivax
      infections, and highlights their potential role in malaria immune response in an
      Amazonian population.

PMID- 24139873
TI  - Sorafenib tosylate as a radiosensitizer in malignant astrocytoma.
AB  - Progress in research on the molecular aspects of glioblastoma has yet to provide
      a medical therapy that significantly improves prognosis. Glioblastoma invariably
      progress through current treatment regimens with radiotherapy as a key component.
      Activation of several signaling pathways is thought to be associated with this
      resistance to radiotherapy. Ras activity is exceptionally high in glioblastoma
      and may regulate sensitivity to radiotherapy. Raf-1, a downstream effector of
      Ras, demonstrates a high amount of activity in glioblastoma. Therefore, Raf-1
      inhibition should be considered as a mechanism to increase the effectiveness of
      radiotherapy in treatment regimen. In vitro analysis was performed with a novel
      Raf-1 kinase inhibitor (BAY 54-9085) in culture with the glioblastoma cell line
      U1242. The cell line was treated in serum-containing media and analyzed for the
      effect of the BAY 54-9085 alone and BAY 54-9085 combined with radiation on cell
      death. BAY 54-9085 displayed a cytocidal effect on glioblastoma cells following a
      3 day incubation with the drug in serum-containing media. A dose of 2.5 MUM
      displayed moderate cell death which significantly increased with a dose of 5.0
      MUM. In addition, glioblastoma cells treated with both the BAY 54-9085 and gamma
      radiation displayed a significant increase in cell death (85.5%) as compared to
      either BAY 54-9085 (73.1%) or radiation (34.4%) alone. Radiation therapy is a key
      component of treatment for glioblastoma. A novel Raf-1 inhibitor displayed in
      vitro evidence of synergistically increasing cell death of glioblastoma cells in
      combination with radiation.

PMID- 24139874
TI  - Multifunctional and potent roles of the 3-hydroxypropoxy group provide
      eldecalcitol's benefit in osteoporosis treatment.
AB  - Eldecalcitol (1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3, [developing
      code: ED-71]), a new osteoporosis treatment drug that was recently approved in
      Japan, is a best-in-class drug in the class of calcitriol (1alpha,25
      dihydroxyvitamin D3) and its prodrug alfacalcidol (1alpha-hydroxyvitamin D3),
      which have been used to treat osteoporosis for 30 years. In a comparative Phase
      III clinical study with alfacalcidol in osteoporosis patients, eldecalcitol
      demonstrated superior efficacy in the endpoints of increment of bone mineral
      density and reduction of bone fracture with equivalent safety to alfacalcidol.
      Eldecalcitol was discovered by searching synthetic analogs of calcitriol and
      alfacalcidol, and its main structural characteristic is having the 3
      hydroxypropoxy group at the 2beta-position. This review discusses why introducing
      the group leads to excellent efficacy and safety in osteoporosis treatment and
      elucidates the functional roles of the 3-hydroxypropoxy group. Briefly, the
      functional roles of the group are, first, realizing the metabolism switching in
      which eldecalcitol shows resistance to CYP24A1 and is metabolized in the liver;
      second, increasing the affinity to the serum carrier protein and prolonging the
      half-life to 53h; and third, stabilizing the eldecalcitol-receptor complex. Taken
      together, these functional roles of the 3-hydroxypropoxy group are beneficial in
      osteoporosis treatment. This review attempts to give a detailed account of the
      mode of action of eldecalcitol by clarifying these multifunctional roles of the 3
      hydroxypropoxy group from the medicinal chemist's perspective. 

PMID- 24139875
TI  - Induction of FKBP51 by aldosterone in intestinal epithelium.
AB  - Screening female rat distal colon preparations for aldosterone-induced genes
      identified the Hsp90-binding immunophilin FKBP51 as a major aldosterone-induced
      mRNA and protein. Limited induction of FKBP51 was observed also in other
      aldosterone-responsive tissues such as kidney medulla and heart. Ex vivo
      measurements in colonic tissue have characterized time course, dose response and
      receptor specificity of the induction of FKBP51. FKBP51 mRNA and protein were
      strongly up regulated by physiological concentrations of aldosterone in a late
      (greater than 2.5h) response to the hormone. Maximal increase in FKBP51 mRNA
      requires aldosterone concentrations that are higher than those needed to fully
      occupy the mineralocorticoid receptor (MR). Yet, the response is fully inhibited
      by the MR antagonist spironolactone and not inhibited and even stimulated by the
      glucocorticoid receptor (GR) antagonist RU486. These and related findings cannot
      be explained by a simple activation and dimerization of either MR or GR but are
      in agreement with response mediated by an MR-GR heterodimer. Overexpression or
      silencing FKBP51 in the kidney collecting duct cell line M1 had little or no
      effect on the aldosterone-induced increase in transepithelial Na(+) transport. 

PMID- 24139876
TI  - Ultrasound and microwave assisted synthesis of dihydroxyacetophenone derivatives
      with or without 1,2-diazine skeleton.
AB  - A thorough study concerning O-alkylation and alpha-bromination of
      dihydroxyacetophenone (DA) and N-alkylation of 1,2-diazine, under ultrasound (US)
      and microwave (MW) irradiation as well as under conventional thermal heating (TH)
      is presented. Under US and MW irradiation the yields are higher, the amount of
      used solvent decreases substantially, the reaction time decreases considerable
      (from hours or days to minutes) and the consumed energy decreases, consequently
      the O-alkylation, alpha-bromination and N-alkylation methods could be considered
      environmentally friendly. A selective and efficient way to either bis-O
      alkylation or mono-O-alkylation of DA has been found, the relative position of
      the two hydroxyl groups on the phenyl moiety being compulsory. A selective and
      efficient way for alpha-bromination in heterogeneous catalysis of DA derivatives
      under US irradiation is presented. The N-alkylation reaction of DA under US and
      MW irradiation proved to be the most convenient setup procedure for these types
      of reactions. Overall, the use of US proved to be more efficient than MW or TH. 

PMID- 24139872
TI  - Progress in translational research on intracerebral hemorrhage: is there an end
      in sight?
AB  - Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for
      which specific therapies and treatments remain elusive. To address this, many
      recent experimental and translational studies of ICH have been conducted, and
      these have led to several ongoing clinical trials. This review focuses on the
      progress of translational studies of ICH including those of the underlying causes
      and natural history of ICH, animal models of the condition, and effects of ICH on
      the immune and cardiac systems, among others. Current and potential clinical
      trials also are discussed for both ICH alone and with intraventricular extension.

PMID- 24139877
TI  - Amanitin and phallotoxin concentration in Amanita phalloides var. alba mushroom.
AB  - Although rarely seen, Amanita phalloides var. alba, a variety of A. phalloides
      type mushrooms, causes mushroom poisoning resulting in death. Since it is
      frequently confused with some edible mushrooms due to its white colored cap and
      macroscopic appearance, it becomes important in toxicological terms. Knowledge of
      the toxin amount contained in this mushroom type is invaluable in the treatment
      of cases involving poisoning. In this study, we examined the toxin levels of
      various parts of the A. phalloides var. alba mushroom growing Duzce region of
      Turkey. Toxin analyses were carried out for A. phalloides var. alba, which were
      collected from the forests Duzce region of Turkey in 2011, as a whole and also
      separately in its spore, pileus, gills, stipe and volva parts. The alpha
      amanitin, beta amanitin, gamma amanitin, phalloidin and phallacidine analyses of
      the mushrooms were carried out using the RP-HPLC method. A genetic analysis of
      the mushroom showed that it had similar genetic characteristics as A. phalloides
      and was a variety of it. The lowest toxins quantity was detected in spores, volva
      and stipe among all parts of the mushroom. The maximum amount of amatoxins was
      measured in the gills. The pileus also contained a high amount of amatoxins.
      Generally, amatoxins and phallotoxin concentrations were lower as compared to A.
      phalloides, but interestingly all toxins other than gamma toxin were higher in
      the spores of A. phalloides var. alba. The amount of toxin in all of its parts
      had sufficient concentrations to cause death. With this study, the amatoxin and
      phallotoxin concentrations in A. phalloides var. alba mushroom and in its parts
      have been revealed in detail for the first time. 

PMID- 24139878
TI  - An optimized binary typing panel improves the typing capability for Campylobacter
      jejuni.
AB  - Campylobacter jejuni is a frequent bacterial pathogen causing gastroenteritis
      worldwide. We report here a mathematically optimized combination of 10 loci
      selected from 2 previously published binary typing panels. The optimized
      combination offers advantages of higher differentiation capability, simplicity,
      cost-effectiveness, and portability for routine surveillance and outbreak
      investigations of C. jejuni. 

PMID- 24139879
TI  - Soluble B7-H3 elevations in hospitalized children with Mycoplasma pneumoniae
      pneumonia.
AB  - The purpose of this study is to explore the associations between soluble B7-H3
      (sB7-H3) and cytokines, clinical characteristics and laboratory findings. Thirty
      two children with Mycoplasma pneumoniae pneumonia diagnosed by both positive
      serology and PCR were admitted to Children's Hospital affiliated to Soochow
      University. These children were enrolled and evaluated from May 2012 through
      September 2012. Soluble B7-H3 level and cytokines (tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma, interleukin (IL)-4, IL-10) were determined by
      enzyme-linked immunosorbent assay technique. Meanwhile, clinical parameters
      including laboratory findings were obtained. Soluble B7-H3 level was
      significantly increased in patients with M. pneumoniae pneumonia compared with
      the levels of sB7-H3 in control subjects (4.94 +/- 2.69 vs. 3.42 +/- 1.48, ng/mL;
      P = 0.032). Furthermore, level of sB7-H3 was correlated with TNF-alpha level in
      plasma in patients with M. pneumoniae pneumonia (rp = 0.667; P < 0.001) as well
      as level of sB7-H3 in M. pneumoniae pneumonia subjects was also correlated with
      duration of symptoms (rp = 0.607; P < 0.001), percentage of neutrophil cells (rp
      = 0.657; P < 0.001), and C-reactive protein level (rs = 0.445; P = 0.011). Level
      of sB7-H3 was decreased after treatment (6.08 +/- 3.07 vs. 3.55 +/- 1.58, ng/mL;
      P = 0.019). Soluble B7-H3 maybe plays an important role in immunopathogenesis of
      M. pneumoniae pneumonia, especially for increasing TNF-alpha concentration and
      activation neutrophils. 

PMID- 24139880
TI  - Continuous versus intermittent infusion of cefepime in neurosurgical patients
      with post-operative intracranial infections.
AB  - Cefepime is administered as an intermittent infusion (II); however, continuous
      infusion (CI) may be advantageous because beta-lactam antibiotics exhibit time
      dependent antibacterial activity. This retrospective, non-randomised, comparative
      study included 68 neurosurgical patients with post-operative intracranial
      infections treated with 4g/day cefepime over 24h as a CI (n=34) or 2g every 12h
      as II (n=34). CI controlled the intracranial infection more rapidly and
      effectively than II (6.6+/-1.9 days vs. 7.8+/-2.6 days; P=0.036). By considering
      the minimum inhibitory concentrations (MICs) to be 4MUg/mL and 8MUg/mL, the
      percentage of time when the cefepime plasma or CSF concentrations were higher
      than the MIC (%T>MIC) was calculated for each patient. For plasma cefepime
      concentrations, the %T(>MIC) in the CI group was higher than in the II group (for
      MICs of 8MUg/mL, 100% vs. 75%, respectively). The mean calculated area under the
      curve (AUC) in the CI group was similar to the II group (1197.99+/-72.15MUgh/mL
      vs. 890.84+/-140.78MUgh/mL; P=0.655). For CSF cefepime concentrations, the
      %T(>MIC) in the CI group was higher than in the II group (for MICs of 4MUg/mL and
      8MUg/mL, 83.3% and 75% vs. 25% and 0%, respectively). The mean calculated AUC for
      the CI group was higher than the II group (220.56+/-13.59MUgh/mL vs. 86.34+/
      5.69MUgh/mL; P=0.003). Therefore, CI of cefepime significantly enhanced the
      antibacterial effect and reduced the treatment duration in neurosurgical patients
      with post-operative intracranial infections.

PMID- 24139881
TI  - IQG-607 abrogates the synthesis of mycolic acids and displays intracellular
      activity against Mycobacterium tuberculosis in infected macrophages.
AB  - In this work, the antitubercular activity of a pentacyano(isoniazid)ferrate(II)
      compound (IQG-607) was investigated using a macrophage model of Mycobacterium
      tuberculosis infection. Importantly, treatment of M.-tuberculosis-infected
      macrophages with IQG-607 significantly diminished the number of CFU compared with
      the untreated control group. The antitubercular activity of IQG-607 was similar
      to that observed for the positive control drugs isoniazid and rifampicin.
      Nevertheless, higher concentrations of IQG-607 produced a significantly greater
      reduction in bacterial load compared with the same concentrations of isoniazid.
      Analysis of the mechanism of action of IQG-607 revealed that the biosynthesis of
      mycolic acids was blocked. The promising activity of IQG-607 in infected
      macrophages and the experimental determination of its mechanism of action may
      help in further studies aimed at the development of a new antimycobacterial
      agent.

PMID- 24139882
TI  - Molecular study of quinolone resistance mechanisms and clonal relationship of
      Salmonella enterica clinical isolates.
AB  - In the last few years, the number of Salmonella enterica strains resistant to
      nalidixic acid has steadily increased. In a previous study, the quinolone
      susceptibility phenotype and genotype of 38 S. enterica clinical isolates (19 S.
      enterica serovar Typhimurium and 19 S. enterica serovar Enteritidis) were
      determined. Forty-two percent of the isolates showed nalidixic acid resistance
      associated with a mutation in gyrA together with putative overexpression of
      efflux pump(s). In this study, mutations in the quinolone resistance-determining
      region (QRDR) of parE and the regulators of AcrAB (acrR, marRAB, soxRS and ramR)
      were analysed. Intracellular accumulation of ciprofloxacin and nalidixic acid was
      determined. Gene expression of the efflux pump components acrB, tolC, acrF and
      emrB was also assessed. In addition, an epidemiological study of the isolates by
      multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) was
      performed. No mutations were detected in parE, whereas two amino acid
      substitutions were found in two susceptible strains in MarR (I84L) and AcrR
      (N214T) in one strain each, although both were suggested to be polymorphisms. No
      changes in the gene expression of acrB, tolC, acrF and emrB were detected between
      nalidixic-acid-resistant and -susceptible strains. Intracellular accumulation was
      not useful to reveal differences. Epidemiological analysis showed an important
      clonal relatedness among the S. Enteritidis isolates, whereas major divergence
      was seen for S. Typhimurium. Altogether, these results suggest the presence of
      previously undiscovered drug efflux pump(s) and confirm the high clonality of S.
      Enteritidis and the genetic divergence of S. Typhimurium. 

PMID- 24139883
TI  - Antibiotic non-susceptibility among Streptococcus pneumoniae and Haemophilus
      influenzae isolates identified in African cohorts: a meta-analysis of three
      decades of published studies.
AB  - Management of community-acquired pneumonia caused by Streptococcus pneumoniae and
      Haemophilus influenzae type B (Hib) can be complicated by emerging antimicrobial
      non-susceptibility. We conducted a meta-analysis to examine the antibiotic
      susceptibility of community-acquired invasive infections with S. pneumoniae and
      Hib in Africa from 1978 to 2011. With the notable exceptions of widespread
      trimethoprim/sulfamethoxazole (SXT) and tetracycline non-susceptibility, the
      majority of pneumococci remain susceptible to ampicillin/amoxicillin. However,
      23.8% of pneumococcal meningitis isolates are non-susceptible to penicillin.
      Similarly, Hib isolates show non-susceptibility to SXT, tetracycline,
      erythromycin and chloramphenicol. beta-Lactamase production among Hib isolates is
      increasing, a new observation for Africa, but is mitigated somewhat by Hib
      vaccination scale-up. In summary, pneumococcal susceptibility to amoxicillin
      remains high throughout Africa, and amoxicillin can be effectively and safely
      used as first-line treatment for childhood pneumonia. Data support first-line
      treatment of bacterial meningitis with ceftriaxone or cefotaxime. 

PMID- 24139884
TI  - Comparative activities of selected fluoroquinolones against dynamic populations
      of Actinobacillus pleuropneumoniae in an in vitro model of time-kill continuous
      culture experiment.
AB  - The aim of the current study was to demonstrate and compare the impact of
      different pharmacokinetics of marbofloxacin, enrofloxacin and difloxacin on their
      antimicrobial effects, their killing and re-growth kinetics, and the population
      dynamics of Actinobacillus pleuropneumoniae clinical isolates in an in vitro
      dynamic model. Selected clinical isolates of A. pleuropneumoniae and three
      fluoroquinolones at a range of simulated AUC(24)/MIC ratios of multiple doses
      were investigated. At the same simulated AUC(24)/MIC ratios of the three
      fluoroquinolones, the killing re-growth profile and I(E) values (intensity of the
      antimicrobial effect) revealed strain- and fluoroquinolone-specific effects. For
      example, a 31% lower I(E) of difloxacin was observed in AppK5 (biofilm-former)
      than in AppK2 (biofilm-non-former) at the same AUC(24)/MIC ratio of 120 h. In
      addition, losses in A. pleuropneumoniae susceptibility of both strains by the
      three fluoroquinolones were observed. AUC(24)/MPC ratios of 20.89 and 39.81 for
      marbofloxacin, 17.32 and 19.49 for enrofloxacin and 31.62 and 60.25 for
      difloxacin were estimated to be protective against the selection of AppK2 and
      AppK5 strain mutants, respectively. Integration of these in vitro data with
      published pharmacokinetics revealed the inadequacy of the conventional clinical
      doses of the three drugs to attain the above protective values for minimum
      biofilm eradication concentration (MBEC) and concentration to prevent growth of
      90% of the mutant subpopulation (MPC(90)). In conclusion, the results suggest
      optimising doses could suffice for resistant mutants control, while for biofilm
      forming strains combination with biofilm-disrupting agents to reduce the MBEC to
      achieve AUC/MBEC ratios within the possible dosing regimens is desired.

PMID- 24139885
TI  - Molecular characterisation of a multidrug resistance conjugative plasmid from
      Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is a major causative agent of gastroenteritis and is the
      leading cause of food-borne illness in Hong Kong. Recent studies of resistance to
      extended-spectrum beta-lactams and fluoroquinolones in V. parahaemolyticus have
      caused huge concern. This work reports the characterisation of a multidrug
      resistance conjugative plasmid in V. parahaemolyticus isolated from shrimp
      samples from Hong Kong. The plasmid is ca. 200 kb and carries multidrug
      resistance genes, including a novel plasmid-mediated quinolone resistance gene
      qnrVC6 surrounded by several known and novel insertion sequence (IS) elements, an
      extended-spectrum beta-lactamase gene bla(PER-1) mediated by ISCR1, and a ca. 3
      kb four-gene cassette (aacA3, catB2, dfrA1 and aadA1) class 1 integron.
      Transmission of this multidrug resistance conjugative plasmid among Vibrio spp.
      would compromise the effectiveness of Vibrio infection control and pose a huge
      threat to public health.

PMID- 24139886
TI  - Potential cellular targets and antibacterial efficacy of atmospheric pressure non
      thermal plasma.
AB  - Atmospheric pressure non-thermal plasma (APNTP) has been gaining increasing
      interest as a new alternative antibacterial approach. Although this approach has
      demonstrated promising antibacterial activity, its exact mechanism of action
      remains unclear. Mechanistic elucidation of the antimicrobial activity will
      facilitate development and rational optimisation of this approach for potential
      medical applications. In this study, the antibacterial efficacy of an in-house
      built APNTP jet was evaluated alongside an investigation of the interactions
      between APNTP and major cellular components in order to identify the potential
      cellular targets involved in plasma-mediated bacterial destruction mechanisms.
      The investigated plasma jet exhibited excellent, rapid antibacterial activity
      against a selected panel of clinically significant bacterial species including
      Bacillus cereus, meticillin-resistant Staphylococcus aureus (MRSA), Escherichia
      coli and Pseudomonas aeruginosa, all of which were completely inactivated within
      2 min of plasma exposure. Plasma-mediated damaging effects were observed, to
      varying degrees, on all of the investigated cellular components including DNA, a
      model protein enzyme, and lipid membrane integrity and permeability. The
      antibacterial efficacy of APNTP appears to involve a multiple-target mechanism,
      which potentially reduces the likelihood of emergence of microbial resistance
      towards this promising antimicrobial approach. However, cellular membrane damage
      and resulting permeability perturbation was found to be the most likely rate
      determining step in this mechanism.

PMID- 24139887
TI  - Ertapenem: lack of allergic reactions in hospitalised adults reporting a history
      of penicillin allergy.

PMID- 24139888
TI  - Placental leptin in HIV-associated preeclampsia.
AB  - OBJECTIVE: HIV-associated preeclampsia reflects a combination of opposing
      influences on the immune status. The adipocyte hormone leptin has been implicated
      in the pathophysiology of preeclampsia and in enhancing immunity. This study is
      the first, to our knowledge, to determine whether leptin levels in the placenta
      differ between HIV-associated normotensive and preeclamptic pregnancies. The
      study also compares leptin levels between the exchange and conducting areas of
      the placenta. STUDY DESIGN: Pregnant women were recruited antenatally and grouped
      as follows: normotensive HIV uninfected (n=30), normotensive HIV infected (n=60),
      preeclamptic HIV uninfected (n=30) and preeclamptic HIV infected (n=60).
      Anthropometric data were collected and placental leptin was analysed by
      immunohistochemistry and ELISA. RESULTS: Leptin levels were similar in the
      central and peripheral regions of the placenta. Leptin immunoreactivity was
      observed amongst the different trophoblast cell populations. Both ELISA and
      immunohistochemistry of the placental exchange villi indicated that leptin levels
      were higher in preeclampsia compared to normotensive pregnancies (p<0.001). HIV
      status had no effect on leptin levels but levels were higher in participants on
      highly active antiretroviral treatment (HAART) compared to those on prophylaxis
      for prevention of mother to child transmission (PMTCT) with normotensive
      (p=0.006) and preeclamptic (p=0.002) pregnancies. The area of immunostaining was
      greater in the exchange compared to the conducting villi in HIV infected and
      uninfected preeclampsia. CONCLUSIONS: This novel study establishes an elevation
      of leptin in preeclamptic placentae, irrespective of HIV status. Leptin elevation
      was not focal in that it occurred in both central and peripheral regions of the
      preeclamptic placenta. This suggests a role of leptin in the pathophysiology of
      preeclampsia.

PMID- 24139889
TI  - Outcomes of an isolated single umbilical artery in singleton pregnancy: a large
      study from the Middle East and Gulf region.
AB  - OBJECTIVE: To assess the frequency and accuracy of prenatal diagnosis of a single
      umbilical artery (SUA) and to compare the fetal and neonatal outcome of isolated
      SUA to that of a normal three-vessel umbilical cord in a population from the
      Middle East and Gulf region. STUDY DESIGN: Data were collected from 37,500
      singleton pregnancies that were scheduled for antenatal care and delivered at
      Security Forces Hospital in Riyadh, Saudi Arabia, between May 2004 and December
      2012. Comparisons between the groups were performed using a chi-square test or a
      Fisher exact test for the categorical variables, and Student's t test or
      Wilcoxon's rank-sum test were used for continuous variables. The Kappa statistic
      was used to study the agreement between the antenatal and final neonatal
      diagnosis of SUA. A univariable analysis was used to calculate the unadjusted and
      adjusted ORs and the 95% CIs expressing the relationship of the normal three
      vessel umbilical cord, the isolated SUA, and each outcome. RESULTS: A total of
      35,249 cases completed the study, including 35,026 cases with normal neonatal
      three-vessel umbilical cords (Group B). SUA was present in 223 (0.63%) neonates
      (0.45% isolated SUA (Group A) and 0.18% non-isolated SUA). The sensitivity,
      specificity, positive predictive value and negative predictive value of using
      prenatal ultrasound for the diagnosis of SUA were 90.58%, 99.9%, 98.5% and
      99.94%, respectively. Neonatal anomaly was present in 2.6% of the fetuses with
      isolated SUA. A pregnancy with isolated SUA was more likely to be complicated
      with polyhydramnios (OR 3.32; CI 1.22-9.04), preterm delivery <34 weeks (OR
      4.662; CI 2.346-9.195), birth weight <10th percentile (OR 2.1; CI 1.44-2.93),
      cesarean delivery for fetal distress (OR 2.72; CI 1.53-4.81), perinatal death (OR
      3.31; CI 1.34-8.12), admission to NICU (OR 2.71; CI 1.87-3.91), and placental
      abnormalities (OR 3.25; CI 2.14-4.93; p value 0.0001) compared to a pregnancy
      with a fetal and neonatal three-vessel cord. CONCLUSION: Isolated SUA is
      associated with anomalies at birth and with an increased risk of adverse
      pregnancy outcomes even in the absence of other anomalies. A pregnancy with this
      complication should receive close fetal monitoring for growth and fetal
      wellbeing.

PMID- 24139890
TI  - Lesions to the prefrontal performance-monitoring network disrupt neural
      processing and adaptive behaviors after both errors and novelty.
AB  - Unexpected events can have internal causes (action errors) as well as external
      causes (perceptual novelty). Both events call for adaptations of ongoing
      behavior, resulting, amongst other things, in post-error and post-novelty slowing
      (PES/PNS) of reaction times (RT). Both types of events are processed in
      prefrontal brain areas, indexed by event-related potentials (ERPs): Errors are
      followed by a complex of ERPs comprised of the error-related negativity (ERN) and
      error positivity (Pe), whereas novels are followed by a N2/P3 complex. However,
      despite those overlapping properties, past neuroscientific studies of both types
      of events resulted in largely separate branches of research. Only recently have
      theoretical efforts proposed overlapping neuronal networks for the computation of
      'unexpectedness' in general. Crucially, in a recent study, we have shown that
      both errors and novelty are indeed processed in the same neuronal network in the
      human brain: the prefrontal-cingulate performance-monitoring network (PCMN)
      underlying the ERN also explained significant parts of the N2/P3 complex. Here,
      we attempt to take this research further by investigating the causal role of the
      PCMN in both error and novelty processing. Eight patients with ischemic lesions
      to the PCMN and eight control participants performed a version of the flanker
      task in which they made errors, while also being presented with unexpected action
      effects on a subset of otherwise correct trials. In line with our predictions,
      lesions to the PCMN lead to significant reductions in ERP amplitude following
      both errors and perceptual novelty. Also, while the age-matched control
      participants showed the expected pattern of adaptive RT slowing to both errors
      and novelty, patients did not exhibit adaptive slowing behaviors following either
      event. These results support recent theoretical accounts according to which a
      general PCMN reacts to surprising events, regardless of valence and/or source of
      the unexpectedness. 

PMID- 24139891
TI  - Unexplained lower limb pain in Parkinson's disease: a phenotypic variant of
      "painful Parkinson's disease".
AB  - Unexplained pain is a key non-motor symptom (NMS) of Parkinson's disease (PD)
      that is prevalent throughout the condition and often unrecognized and under
      treated. We have identified a cluster of patients with unexplained refractory and
      intrusive lower limb pain. METHODS: Patients with 'unexplained' pain were
      identified from a survey using a non-motor symptom questionnaire and scale
      (NMSQuest, NMSS). Patients reporting unexplained severe proximal lower limb pain
      were then assessed using a newly devised PD pain scale. Co-morbid conditions were
      excluded and all had lower spine imaging. RESULTS: From a cohort of 225 patients
      we have identified 22 with unexplained lower limb pain described as persistent
      leg pain ranging from unilateral to bilateral sometimes associated with whole
      body pain. None had significant spinal pathology or evidence of large fiber
      neuropathy. 14 were on regular analgesics with poor effect while 9 took morphine
      based remedies. Severe unremitting pain led to accidental overdose and death in
      one patient. All took a combination of levodopa and dopamine agonist treatment
      including 3 on intrajejunal levodopa infusion. All had high NMSQuest (mean =
      17/30) and NMSS (mean = 95 (normal range 30-60)) scores. CONCLUSIONS: We believe
      that unexplained lower limb pain is a specific non-motor phenotype in Parkinson's
      disease that is problematic and often undisclosed. This may be a variant of
      central pain and merits recognition.

PMID- 24139892
TI  - Extrascleral extension of choroidal melanoma: post-enucleation high-dose-rate
      interstitial brachytherapy of the orbit.
AB  - PURPOSE: To investigate if orbital extension of uveal melanoma can be treated
      with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: This study is a
      retrospective analysis of the results of a clinical case series was performed on
      10 patients. Each underwent primary enucleation for uveal melanoma, was
      discovered to have orbital extension, and consented for HDR brachytherapy. By
      American Joint Committee on Cancer (AJCC) initial tumor grading, there was one
      each (T1c, T2c, T2d, and T3d, three T4c, and two T4d-staged uveal melanomas. One
      was AJCC-staged R2 due to orbital recurrence presenting 16 months after
      enucleation. (192)Ir HDR brachytherapy involved transcutaneous circumferential
      orbital incisions allowing for evenly spaced brachytherapy catheters into the
      orbit. A target dose of 32.85 Gy (range, 32.85-34 Gy) was delivered in 9-10 twice
      daily fractions (range, 3.4-3.65 Gy per fraction) over 5 consecutive days. Data
      analysis included but was not limited to radiation therapy methods, local tumor
      control, side effects, and metastatic rate. RESULTS: In the 9 patients who
      tolerated treatment, there has been no orbital recurrence at a median follow-up
      of 18 months (range, 1-62 months). Four patients died of metastatic disease (one
      presented with a treated solitary liver metastasis before brachytherapy). There
      was no significant eyelash or eyebrow loss. There was no radiation-induced eyelid
      erythema, orbital infection, or contracted sockets. All orbits accepted and
      maintained ocular prostheses. CONCLUSIONS: Brachytherapy was used as an
      alternative to external beam radiation treatment for postenucleation orbital
      melanoma. This series reports complete local control, few side effects, and
      excellent cosmetic results.

PMID- 24139893
TI  - Repair of retrograde ascending dissection after descending stent grafting.
AB  - OBJECTIVE: Retrograde dissection is now recognized as an important complication
      after thoracic endovascular aortic repair (TEVAR), but its treatment is poorly
      understood. Our objectives were to investigate the risks, describe the repair
      methods, and assess the outcomes of this complication. METHODS: From 2000 to
      2012, 766 patients underwent TEVAR. Of these patients, 14 (1.8%), plus 1 who had
      undergone TEVAR elsewhere (n = 15), developed retrograde dissection after stent
      grafting. They had undergone TEVAR for distal aortic dissection in 7, intramural
      hematoma in 5, aneurysm in 2, and transection in 1. Their mean age was 65 +/- 9
      years. At the initial TEVAR, the left subclavian artery was covered in 9, the
      mean stent graft diameter was 34 +/- 2 mm, and >1 device was used in 8 patients.
      The site of entry tear was at the greater curvature in 11 and lesser curvature in
      4. One patient ruptured and died 12 days after TEVAR and never made it to the
      operating room. The other 14 underwent proximal aortic repair. The median
      interval between TEVAR and repair of retrograde dissection was 6 months; 3
      patients presented within 1 month. The repair techniques included reverse frozen
      elephant trunk in 5, total arch repair in 4, ascending or hemiarch repair in 4,
      and ascending TEVAR in 1. Concomitant procedures included aortic valve repair in
      4, replacement in 2, root remodeling in 1, and coronary bypass in 1. RESULTS: No
      operative mortality occurred. One patient underwent reoperation for bleeding. Two
      required a tracheostomy for respiratory failure. However, no renal failure,
      stroke, or spinal injury occurred. At a median follow-up of 26 months, 4 aortic
      reoperations had occurred: 1 distal stent graft extension for type 1b endoleak, 2
      hybrid thoracoabdominal completion repairs for growth of residual distal disease,
      and 1 emergency TEVAR for aortobronchial fistula. The latter patient died of
      septic complications, and 3 other late noncardiac deaths occurred. CONCLUSIONS:
      Retrograde ascending dissection can present as an early or a late complication
      after descending stent grafting because of aortic instability or disease
      progression and has usually been associated with descending dissection or
      intramural hematoma. It is a life-threatening complication that can be managed
      safely with early recognition and rapid delivery of open or hybrid repair.

PMID- 24139894
TI  - Discussion.

PMID- 24139895
TI  - Delayed esophageal diverticulum formation after stent-based treatment of
      perforation.

PMID- 24139896
TI  - Minimal-dose computed tomography is superior to chest x-ray for the follow-up and
      treatment of patients with resected lung cancer.
AB  - OBJECTIVES: A minimal-dose computed tomography scan of the thorax (MnDCT)
      delivers a radiation dose comparable with a chest x-ray (CXR). We hypothesized
      that in patients with completely resected lung cancer, surveillance with MnDCT,
      when compared with CXR, leads to earlier detection and a higher rate of treatment
      of new or recurrent lung cancer. METHODS: After lung cancer resection, patients
      prospectively were enrolled for surveillance with MnDCT and CXR at 3, 6, 12, 18,
      24, 36, 48, and 60 months. Images were interpreted by different blinded
      radiologists. When new or recurrent cancer was suspected, standard-dose CT and/or
      a tissue biopsy were performed for confirmation. RESULTS: Between 2007 and 2012,
      271 patients were included and 1137 pairs of CXR and MnDCT were analyzed. MnDCT
      was more sensitive (94% vs 21%; P < .0001) and had a higher negative predictive
      value (99% vs 96%; P = .007) than CXR for the diagnosis of new or recurrent lung
      cancer. The prevalence of new or recurrent lung cancer was 23.2% (63 of 271), of
      whom 78% (49 of 63) had asymptomatic disease. The majority of asymptomatic
      patients (75%; 37 of 49) were treated with curative intent and had a median
      survival of 69 months. The remainder of patients received palliative treatment
      (24%; 12 of 49) and had a median survival of 25 months (P < .0001). CONCLUSIONS:
      After curative resection of lung cancer, MnDCT is superior to CXR for the
      detection of new or recurrent lung cancer. The majority of new or recurrent
      cancer was detected by MnDCT at an asymptomatic phase, allowing for curative
      treatment, leading to a long survival.

PMID- 24139897
TI  - Rhythm outcome predictors after concomitant surgical ablation for atrial
      fibrillation: a 9-year, single-center experience.
AB  - OBJECTIVES: Concomitant surgical ablation is a safe and feasible procedure,
      recommended by the guidelines for patients with atrial fibrillation (AF)
      undergoing cardiac surgery. We performed a single-center data analysis to
      identify the predictors of rhythm outcome in such patients. METHODS: From January
      2003 to January 2012, 503 patients with persistent (n = 296, 58.8%) or paroxysmal
      (n = 207, 41.2%) AF underwent concomitant surgical AF ablation. The lesions were
      limited to a pulmonary vein isolation (n = 76, 15.1%), a more complex left atrial
      lesion set (n = 353, 70.2%), or biatrial lesions (n = 74, 14.7%). Follow-up
      rhythm evaluations were based on either 24-hour Holter electrocardiograms or
      event recorder interrogation at 3, 6, and 12 months postoperatively. A sinus
      rhythm (SR) immediately postoperatively was defined as the first documented
      rhythm after weaning from extracorporeal circulation. RESULTS: The mean patient
      age was 68.0 +/- 9.5 years, and 336 (66.8%) were men. No major ablation-related
      complications occurred. After 1 year of follow-up, 59.9% of all patients were in
      SR, with significantly better results in patients with paroxysmal AF than in
      those with persistent AF (67.3% vs 54.8%, P = .0053). Additional statistically
      significant factors influencing SR after 1 year were left atrial diameter (P =
      .0019), AF duration (P = .018), and immediate postoperative SR (P < .001).
      Regarding only patients with persistent or longstanding-persistent AF, those with
      biatrial lesions had significantly greater rates of conversion to SR than those
      with solitary left atrial ablation (SR, 64.9% vs 51.4%; P = .044) after 12
      months. CONCLUSIONS: The statistically significant predictors for SR after 1 year
      were left atrial diameter, AF duration, preoperative paroxysmal AF, immediate
      postoperative SR, and biatrial ablation for persistent AF.

PMID- 24139898
TI  - Hypermutation of the inactive X chromosome is a frequent event in cancer.
AB  - Mutation is a fundamental process in tumorigenesis. However, the degree to which
      the rate of somatic mutation varies across the human genome and the mechanistic
      basis underlying this variation remain to be fully elucidated. Here, we performed
      a cross-cancer comparison of 402 whole genomes comprising a diverse set of
      childhood and adult tumors, including both solid and hematopoietic malignancies.
      Surprisingly, we found that the inactive X chromosome of many female cancer
      genomes accumulates on average twice and up to four times as many somatic
      mutations per megabase, as compared to the individual autosomes. Whole-genome
      sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from
      healthy individuals and a premalignant myelodysplastic syndrome (MDS) sample
      revealed no X chromosome hypermutation. Our data suggest that hypermutation of
      the inactive X chromosome is an early and frequent feature of tumorigenesis
      resulting from DNA replication stress in aberrantly proliferating cells.

PMID- 24139899
TI  - Association between antibodies to multiple infectious and food antigens and new
      onset schizophrenia among US military personnel.
AB  - INTRODUCTION: Multiple studies have documented immune activation in many
      individuals with schizophrenia suggesting that antigens capable of generating a
      prolonged immune response may be important environmental factors in many cases of
      this disorder. While existing studies have found single-agent associations of
      antibodies to food and neurotropic infectious agents with schizophrenia, a
      simultaneous examination of multiple agents may shed light on agent interactions
      or possible etiopathogenic pathways. METHODS: We used traditional regression and
      novel statistical techniques to examine associations of single and combined
      infectious and food antigens with schizophrenia. We tested 6106 serum samples
      from 855 cases and 1165 matched controls. RESULTS: Higher antibody levels to
      casein were borderline significant in the prediction of schizophrenia (HR=1.08,
      p=0.06). Study participants with higher cytomegalovirus (CMV) IgG antibody levels
      had a reduced risk of developing schizophrenia (HR=0.90; p=0.02). While IgG
      antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human
      herpesvirus-6 (HHV-6) showed no significant independent associations with
      schizophrenia, the increase in antibody levels to several combinations of agents,
      to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18
      34% increase in the risk of developing schizophrenia. CONCLUSION: Certain
      patterns of antibodies, involving some agents, were predictive of developing
      schizophrenia, with the magnitude of association rising when the level of
      antibodies increased to two or more agents. A heightened antibody response to a
      combination of several infectious/food antigens might be an indicator of an
      altered immune response to antigenic stimuli.

PMID- 24139900
TI  - Commentary on "microparticle-associated tissue factor activity in patients with
      metastatic pancreatic cancer and its effect on fibrin clot formation".

PMID- 24139901
TI  - Assessing the bacterial contribution to the plastid proteome.
AB  - Plastids fulfill a variety of different functions (e.g., photosynthesis and amino
      acid biosynthesis) that rely on proteins of cyanobacterial (i.e., endosymbiont),
      noncyanobacterial, and 'host' (eukaryotic) origins. Analysis of plastid proteome
      data from glaucophytes and green algae allows robust inference of protein origins
      and organelle protein sharing across the >1 billion years of Archaeplastida
      evolution. Here, we show that more than one-third of genes encoding plastid
      proteins lack detectable homologs in Cyanobacteria, underlining the taxonomically
      broad contributions to plastid functions. Chlamydiae and Proteobacteria are the
      most significant other bacterial sources of plastid proteins. Mapping of plastid
      proteins to metabolic pathways shows a core set of anciently derived proteins in
      Archaeplastida, with many others being lineage specific and derived from
      independent horizontal gene transfer (HGT) events. 

PMID- 24139902
TI  - Field high-throughput phenotyping: the new crop breeding frontier.
AB  - Constraints in field phenotyping capability limit our ability to dissect the
      genetics of quantitative traits, particularly those related to yield and stress
      tolerance (e.g., yield potential as well as increased drought, heat tolerance,
      and nutrient efficiency, etc.). The development of effective field-based high
      throughput phenotyping platforms (HTPPs) remains a bottleneck for future breeding
      advances. However, progress in sensors, aeronautics, and high-performance
      computing are paving the way. Here, we review recent advances in field HTPPs,
      which should combine at an affordable cost, high capacity for data recording,
      scoring and processing, and non-invasive remote sensing methods, together with
      automated environmental data collection. Laboratory analyses of key plant parts
      may complement direct phenotyping under field conditions. Improvements in user
      friendly data management together with a more powerful interpretation of results
      should increase the use of field HTPPs, therefore increasing the efficiency of
      crop genetic improvement to meet the needs of future generations. 

PMID- 24139903
TI  - Early environmental factors, alteration of epigenetic marks and metabolic disease
      susceptibility.
AB  - The environmental conditions that are experienced in early life can profoundly
      influence human biology and long-term health. Early-life nutrition and stress are
      among the best documented examples of such conditions because they influence the
      adult risk of developing metabolic diseases, such as type 2 diabetes mellitus
      (T2D) and cardiovascular diseases. It is now becoming increasingly accepted that
      environmental compounds including nutrients can produce changes in the genome
      activity that in spite of not altering DNA sequence can produce important, stable
      and transgenerational alterations in the phenotype. Epigenetic changes, in
      particular DNA methylation and histone acetylation/methylation, provide a
      'memory' of developmental plastic responses to early environment and are central
      to the generation of phenotypes and their stability throughout the life course.
      Their effects may only become manifest later in life, e.g. in terms of altered
      responses to environmental challenges. 

PMID- 24139904
TI  - The two faces of Cdk8, a positive/negative regulator of transcription.
AB  - Three cyclin dependent kinases, Cdk7, Cdk8 and Cdk9 are intimately connected with
      the processes of RNA polymerase II dependent transcription initiation and
      elongation in eukaryotic cells. Each of these kinases is part of a larger
      multisubunit complex, TFIIH, Mediator and p-TEFb respectively. Of the three
      kinases, Cdk8 is the most complex given that it has been associated with both
      positive and negative effects on transcription via mechanisms that include
      regulation of transcription factor turnover, regulation of CTD phosphorylation
      and regulation of activator or repressor function. Furthermore, Cdk8 has emerged
      as a key regulator of multiple transcriptional programs linked to nutrient/growth
      factor sensing and differentiation control. As such Cdk8 represents a potentially
      interesting therapeutic drug target. In this review we summarize the current
      state of knowledge on Cdk8 function both in yeast and higher eukaryotes as well
      as discussing the effects of Cdk8 null mutations at the organismal level. 

PMID- 24139905
TI  - The effect of proteolysis on the induction of cell death by monomeric alpha
      lactalbumin.
AB  - alpha-Lactalbumin (alpha-la) is a major whey protein found in milk. Previous data
      suggested that alpha-la has antiproliferative effects in human adenocarcinoma
      cell lines such as Caco-2 and HT-29. However, the cell death inducing alpha-la
      was not a naturally occurring monomer but either a multimeric variant or an alpha
      la:oleic acid complex (HAMLET/BAMLET). Proteolysis showed that both human and
      bovine alpha-la are susceptible to digestion. ELISA assays assessing cell death
      with the native undigested alpha-la fractions showed that undigested protein
      fractions did have a significant cell death effect on CaCo-2 cells. Bovine alpha
      la was also more effective than human alpha-la. A reduction in activity
      corresponded with lower concentrations of the protein and partial digestion and
      fragmentation of the protein using trypsin and pepsin. This suggests that the
      tertiary structure is vital for the apoptotic effect. 

PMID- 24139906
TI  - Respiratory-deficient mutants of the unicellular green alga Chlamydomonas: a
      review.
AB  - Genetic manipulation of the unicellular green alga Chlamydomonas reinhardtii is
      straightforward. Nuclear genes can be interrupted by insertional mutagenesis or
      targeted by RNA interference whereas random or site-directed mutagenesis allows
      the introduction of mutations in the mitochondrial genome. This, combined with a
      screen that easily allows discriminating respiratory-deficient mutants, makes
      Chlamydomonas a model system of choice to study mitochondria biology in
      photosynthetic organisms. Since the first description of Chlamydomonas
      respiratory-deficient mutants in 1977 by random mutagenesis, many other mutants
      affected in mitochondrial components have been characterized. These respiratory
      deficient mutants increased our knowledge on function and assembly of the
      respiratory enzyme complexes. More recently some of these mutants allowed the
      study of mitochondrial gene expression processes poorly understood in
      Chlamydomonas. In this review, we update the data concerning the respiratory
      components with a special focus on the assembly factors identified on other
      organisms. In addition, we make an inventory of different mitochondrial
      respiratory mutants that are inactivated either on mitochondrial or nuclear
      genes. 

PMID- 24139907
TI  - Tumor necrosis factor-alpha (TNF-alpha) -863C/A promoter polymorphism is
      associated with type 2 diabetes in Tunisian population.
AB  - AIMS: Tumor necrosis factor alpha (TNFalpha) plays a key role in orchestrating
      the complex events involved in inflammation and immunity. Accordingly, TNF alpha
      has been implicated in a wide range of autoimmune and infectious diseases, but
      also in conditions such as obesity and insulin resistance. The aim of the present
      study was to investigate the association between the -863C/A polymorphism in the
      promoter of the TNFalpha gene and type 2 diabetes in the Tunisian population.
      METHODS: The polymorphism -863C/A in the TNFalpha gene was determined in 211 type
      2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. RESULTS: A
      significant difference in genotype distribution and allele frequency was observed
      between patients and controls. Patients with type 2 diabetes had significantly
      higher frequency of the CA+AA genotypes compared to controls [35.5% vs. 22.3%; OR
      (95%CI), 1.91 (1.31-2.8); p=0.001]. The type 2 diabetes patient group showed a
      significant higher frequency of the A allele compared to the controls (0.19 vs.
      0.11; p=0.001). After adjustment by a stepwise logistic regression method,
      hypertension, dyslipidemia, and CA+AA genotype were found to be significantly
      associated with T2D. CONCLUSION: The present study showed a significant and
      independent association between the -863C/A polymorphism of the TNFalpha gene and
      type 2 diabetes in the Tunisian population.

PMID- 24139908
TI  - Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells
      delineates the regulatory roles of microRNA in hematopoiesis.
AB  - In the process of human hematopoiesis, precise regulation of the expression of
      lineage-specific gene products is critical for multiple cell-fate decisions that
      govern cell differentiation, proliferation, and self-renewal. Given the important
      role of microRNAs (miRNAs) in development and differentiation, we examined the
      global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis
      and found 49 miRNAs to be differentially expressed, with functional roles in
      cellular growth and proliferation, and apoptosis. miR-18a was upregulated during
      erythropoiesis and downregulated during megakaryopoiesis. miR-145 was upregulated
      during granulopoiesis and down regulated during erythropoiesis. Megakaryopoitic
      differentiation resulted in significant alteration in the expression of many
      miRNAs that are believed to play critical roles in the regulation of B and T cell
      differentiation. Target prediction analyses on three different miRNA databases
      indicated that TargetScan outperformed microCosm and miRDB in identifying
      potential miRNA targets associated with hematopoietic differentiation process. An
      integrated analysis of the observed miRNAs and messenger RNAs (mRNAs) resulted in
      87 highly correlated miRNA-mRNA pairs that have major functional roles in
      cellular growth and proliferation, hematopoietic system development, and Wnt/B
      catenin and Flt 3 signaling pathways. We believe that this study will enhance our
      understanding on the regulatory roles of miRNA in hematopoiesis by providing a
      library of mRNA-miRNA networks. 

PMID- 24139909
TI  - CYP345E2, an antenna-specific cytochrome P450 from the mountain pine beetle,
      Dendroctonus ponderosae Hopkins, catalyses the oxidation of pine host monoterpene
      volatiles.
AB  - The mountain pine beetle (MPB, Dendroctonus ponderosae Hopkins) is a significant
      pest of western North American pine forests. This beetle responds to pheromones
      and host volatiles in order to mass attack and thus overcome the terpenoid
      chemical defences of its host. The ability of MPB antennae to rapidly process
      odorants is necessary to avoid odorant receptor saturation and thus the enzymes
      responsible for odorant clearance are an important aspect of host colonization.
      An antenna-specific cytochrome P450, DponCYP345E2, is the most highly expressed
      transcript in adult MPB antenna. In in vitro assays with recombinant enzyme,
      DponCYP345E2 used several pine host monoterpenes as substrates, including (+)-(3)
      carene, (+)-beta-pinene, (-)-beta-pinene, (+)-limonene, (-)-limonene, (-)
      camphene, (+)-alpha-pinene, (-)-alpha-pinene, and terpinolene. The substrates
      were epoxidized or hydroxylated, depending upon the substrate. To complement
      DponCYP345E2, we also functionally characterized the NADPH-dependent cytochrome
      P450 reductase and the cytochrome b5 from MPB. DponCYP345E2 is the first
      cytochrome P450 to be functionally characterized in insect olfaction and in MPB. 

PMID- 24139910
TI  - Prenatal stress and subsequent exposure to chronic mild stress in rats;
      interdependent effects on emotional behavior and the serotonergic system.
AB  - Exposure to prenatal stress (PS) can predispose individuals to the development of
      psychopathology later in life. We examined the effects of unpredictable chronic
      mild stress (CMS) exposure during adolescence on a background of PS in male and
      female Sprague-Dawley rats. PS induced more anxiety-like behavior in the elevated
      zero maze in both sexes, an effect that was normalized by subsequent exposure to
      CMS. Moreover, PS was associated with increased depression-like behavior in the
      forced swim test in males only. Conversely, sucrose intake was increased in PS
      males, whilst being decreased in females when consecutively exposed to PS and
      CMS. Hypothalamo-pituitary-adrenal (HPA) axis reactivity was affected in males
      only, with higher stress-induced plasma corticosterone levels after PS. Markedly,
      CMS normalized the effects of PS on elevated zero maze behavior as well as basal
      and stress-induced plasma corticosterone secretion. At the neurochemical level,
      both PS and CMS induced various sex-specific alterations in serotonin (5-HT) and
      tryptophan hydroxylase 2 (TPH2) immunoreactivity in the dorsal raphe nucleus,
      hippocampus and prefrontal cortex with, in line with the behavioral observations,
      more profound effects in male offspring. In conclusion, these findings show that
      prenatal maternal stress in Sprague-Dawley rats induces various anxiety- and
      depression-related behavioral and neuroendocrine changes, as well as alterations
      in central 5-HT and TPH2 function, predominantly in male offspring. Moreover, CMS
      exposure partially normalized the effects of previous PS experience, suggesting
      that the outcome of developmental stress exposure largely depends on the
      environmental conditions later in life and vice versa. 

PMID- 24139911
TI  - [Diagnostic validity of the intraoperative analysis in frozen section of the
      sentinel lymph node in the surgical management of breast cancer].
AB  - OBJECTIVE: The method for intraoperative sentinel lymph node (SLN) evaluation has
      still not been established in breast cancer staging. This study has evaluated the
      diagnostic validity and impact of intraoperative analysis using the frozen
      section (FS) of SLN. MATERIAL AND METHODS: We performed a descriptive study of
      the diagnostic validity of the FS of the SLN in patients with breast cancer and
      selective sentinel node biopsy (SSNB) from October-2006 to October-2012. The
      diagnostic validity indexes were evaluated using sensitivity, specificity,
      positive and negative predictive values and global value. Gold standard was
      considered as the final histopathological results of the biopsies. RESULTS: A
      total of 370 patients were studied. Sensitivity and specificity for detection of
      metastasis by FS in the SLN were 67% and 100%, respectively. Global diagnostic
      validity was 95%. There was a correlation between detection of metastasis and
      tumor size (p<0.05). Twelve of the 15 patients with SLN micro-metastases
      underwent axillary lymph node dissection (ALND). Metastatic lymph nodes were not
      found in any of them. CONCLUSIONS: Intraoperative FS examination of the SLN is a
      useful and reliable predictor of axillary lymph node staging in patients with
      initial stages of breast cancer. FS reduces the need for second interventions, at
      least for most patients who have breast cancer with identifiable positive SLN and
      unequivocal evidence of positive lymph node disease.

PMID- 24139912
TI  - Prevalence of Chagas disease in Brazil: a systematic review and meta-analysis.
AB  - Chagas disease is a major public health problem in Brazil and Latin America.
      During the last years, it has become an emerging problem in North America and
      Europe due to increasing international migration. Here we describe the prevalence
      of Chagas disease in Brazil through a systematic review. We searched national and
      international electronic databases, grey literature and reference lists of
      selected articles for population-based studies on Chagas disease prevalence in
      Brazil, performed from 1980 until September 2012. Forty-two articles with
      relevant prevalence data were identified from a total of 4985 references.
      Prevalence ranged from 0% to 25.1%. Most surveys were performed in the Northeast
      region, especially in the state of Piaui. We observed a high degree of
      heterogeneity in most pooled estimates (I(2)>75%; p<0.001). The pooled estimate
      of Chagas disease prevalence across studies for the entire period was 4.2% (95%
      CI: 3.1-5.7), ranging from 4.4% (95% CI: 2.3-8.3) in the 1980s to 2.4% (95% CI:
      1.5-3.8) after 2000. Females (4.2%; 95% CI: 2.6-6.8), >60 year-olds (17.7%; 95%
      CI: 11.4-26.5), Northeast (5.0%; 95% CI: 3.1-8.1) and Southeast (5.0%; CI: 2.4
      9.9) regions and mixed (urban/rural) areas (6.4%; 95% CI: 4.2-9.4) had the
      highest pooled prevalence. About 4.6 million (95% CI: 2.9-7.2 million) of people
      are estimated to be infected with Trypanosoma cruzi. The small number of studies
      and small-scale samples of the general population in some areas limit
      interpretation, and findings of this review do not necessarily reflect the
      situation of the entire country. Systematic population-based studies at regional
      and national level are recommended to provide more accurate estimates and better
      define the epidemiology and risk areas of Chagas disease in Brazil. 

PMID- 24139913
TI  - Anterior translation and morphologic changes of the ulnar nerve at the elbow in
      adolescent baseball players.
AB  - The effect of repetitive throwing on the ulnar nerve is not clear. There are no
      published imaging studies regarding this issue in adolescent baseball players.
      The purpose of this cross-sectional ultrasonographic study was to use 5- to 10
      MHz frequency ultrasonography to define the anterior translation and flattening
      of the ulnar nerve in different elbow positions. We divided 39 adolescent
      baseball players into two groups, 19 pitchers and 20 fielders, according to the
      amount of throwing. Twenty-four non-athlete junior high school students were also
      included as controls. We ultrasonographically examined each participant's ulnar
      nerve in the cubital tunnel with the elbow extended and at 45 degrees , 90
      degrees  and 120 degrees  of flexion. Anterior translation and flattening of the
      ulnar nerve occurred in all groups. Pitchers had larger-scale anterior
      translation than did controls. In pitchers, the ulnar nerve exhibited more
      anterior movement on the dominant side than on the non-dominant side. The
      anterior subluxation of the ulnar nerve occurred in players without ulnar nerve
      palsy and was not correlated with elbow pain. In addition to the known
      musculoskeletal adaptations of pitchers' elbows, ultrasonography revealed new
      changes in the ulnar nerve, anterior translation and subluxation, after
      repetitive throwing. These changes might also be physiologic adaptations of
      throwing elbows. 

PMID- 24139914
TI  - In vivo measurement of human achilles tendon morphology using freehand 3-D
      ultrasound.
AB  - This study investigated the accuracy of phantom volume and length measurements
      and the reliability of in vivo Achilles tendon (AT) volume, length and cross
      sectional area measurements obtained using freehand 3-D ultrasound. Participants
      (n = 13) were scanned on consecutive days under active and passive loading
      conditions. In vivo AT length was evaluated using a two-point method and an
      approach that accounted for AT curvature (centroid method). Three-dimensional
      ultrasound provided accurate measures of phantom volume and length (mean
      difference = 0.05 mL and 0.2 mm, respectively) and reliable in vivo measures of
      AT volume, length and average cross-sectional area, with all intra-class
      correlations coefficients greater than 0.98. The mean minimally detectable
      changes for in vivo AT volume, two-point length and centroid length were 0.2 mL,
      1.5 mm and 2.0 mm, respectively. Two-point AT length underestimated centroid AT
      length by 0.7 mm, suggesting that the effect of curvature on in vivo AT length is
      negligible. 

PMID- 24139915
TI  - Development of oil-in-gelatin phantoms for viscoelasticity measurement in
      ultrasound shear wave elastography.
AB  - Because tissues consist of solid and fluid materials, their mechanical properties
      should be characterized in terms of both elasticity and viscosity. Although the
      elastic properties of tissue-mimicking phantoms have been extensively studied and
      well characterized in commercially available phantoms, their viscous properties
      have not been fully investigated. In this article, a set of 14 tissue-mimicking
      phantoms with different concentrations of gelatin and castor oil were fabricated
      and characterized in terms of acoustic and viscoelastic properties. The results
      indicate that adding castor oil to gelatin phantoms decreases shear modulus, but
      increases shear wave dispersion. For 3% gelatin phantoms containing 0%, 10%, 20%
      and 40% oil, the measured shear moduli are 2.01 +/- 0.26, 1.68 +/- 0.25, 1.10 +/-
      0.22 and 0.88 +/- 0.17 kPa, and the Voigt-model coupled shear viscosities are
      0.60 +/- 0.11, 0.89 +/- 0.07, 1.05 +/- 0.11 and 1.06 +/- 0.13 Pa.s, respectively.
      The results also confirm that increasing the gelatin concentration increases
      shear modulus. For phantoms containing 3%, 4%, 5%, 6% and 7% gelatin, the
      measured shear moduli are 2.01 +/- 0.26, 3.10 +/- 0.34, 4.18 +/- 0.84, 8.05 +/-
      1.00 and 10.24 +/- 1.80 kPa at 0% oil and 1.10 +/- 0.22, 1.97 +/- 0.20, 3.13 +/-
      0.63, 4.60 +/- 0.60 and 8.43 +/- 1.39 kPa at 20% oil, respectively. The phantom
      recipe developed in this study can be used in validating ultrasound shear wave
      elastography techniques for soft tissues. 

PMID- 24139916
TI  - A 3-D ultrasound imaging robotic system to detect and quantify lower limb
      arterial stenoses: in vivo feasibility.
AB  - The degree of stenosis is the most common criterion used to assess the severity
      of lower limb peripheral arterial disease. Two-dimensional ultrasound (US)
      imaging is the first-line diagnostic method for investigating lesions, but it
      cannot render a 3-D map of the entire lower limb vascular tree required for
      therapy planning. We propose a prototype 3-D US imaging robotic system that can
      potentially reconstruct arteries from the iliac in the lower abdomen down to the
      popliteal behind the knee. A realistic multi-modal vascular phantom was first
      conceptualized to evaluate the system's performance. Geometric accuracies were
      assessed in surface reconstruction and cross-sectional area in comparison to
      computed tomography angiography (CTA). A mean surface map error of 0.55 mm was
      recorded for 3-D US vessel representations, and cross-sectional lumen areas were
      congruent with CTA geometry. In the phantom study, stenotic lesions were properly
      localized and severe stenoses up to 98.3% were evaluated with -3.6 to 11.8%
      errors. The feasibility of the in vivo system in reconstructing the normal
      femoral artery segment of a volunteer and detecting stenoses on a femoral segment
      of a patient was also investigated and compared with that of CTA. Together, these
      results encourage future developments to increase the robot's potential to
      adequately represent lower limb vessels and clinically evaluate stenotic lesions
      for therapy planning and recurrent non-invasive and non-ionizing follow-up
      examinations. 

PMID- 24139917
TI  - Single-particle optical sizing of microbubbles.
AB  - Single-particle optical sizing techniques are being used to determine the size
      distributions of microbubble ultrasound contrast agents and to study the dynamics
      of individual microbubbles during ultrasound stimulation. The goal of this study
      was to compare experimental light obscuration and scattering measurements of
      microbubble size distributions with predictions from generalized Lorenz-Mie
      scattering theory (GLMT). First, we illustrate that a mono-modal size
      distribution can be misrepresented by single-particle light obscuration
      measurements as multi-modal peaks because of non-linearities in the extinction
      cross section-versus-diameter curve. Next, polymer bead standards are measured to
      provide conversion factors between GLMT calculations and experimental flow
      cytometry scatter plots. GLMT calculations with these conversion factors
      accurately predict the characteristic Lissajous-like serpentine scattering plot
      measured by flow cytometry for microbubbles. We conclude that GLMT calculations
      can be combined with optical forward and side scatter measurements to accurately
      determine microbubble size. 

PMID- 24139918
TI  - Optimized shear wave generation using hybrid beamforming methods.
AB  - Elasticity imaging is a medical imaging modality that measures tissue elasticity
      as an aid in the diagnosis of certain diseases. Shear wave-based methods have
      been developed to perform elasticity measurements in soft tissue. These methods
      often use the radiation force mechanism of focused ultrasound to induce shear
      waves in soft tissue such as liver, kidney, breast, thyroid and skeletal muscle.
      The efficiency of the ultrasound beam in producing broadband extended shear waves
      in soft tissue is very important to the widespread use of this modality. Hybrid
      beamforming combines two types of focusing, conventional spherical focusing and
      axicon focusing, to produce a beam for generating a shear wave that has increased
      depth-of-field (DOF) so that measurements can be made with a shear wave with a
      consistent wave front. Spherical focusing is used in many applications to achieve
      high lateral resolution, but has low DOF. Axicon focusing, with a cone-shaped
      transducer, can provide good lateral resolution with large DOF. We describe our
      linear aperture design and beam optimization performed using angular spectrum
      simulations. We performed a large parametric simulation study in which we varied
      the focal depth for the spherical focusing portion of the aperture, the numbers
      of elements devoted to the spherical and axicon focusing portions of the aperture
      and the opening angle used for axicon focusing. The hybrid beamforming method was
      experimentally tested in two phantoms, and shear wave speed measurement accuracy
      and DOF for each hybrid beam were evaluated. We compared our results with those
      for shear waves generated using only spherical focusing. The results of this
      study indicate that hybrid beamforming is capable of producing a beam with
      increased DOF over which accurate shear wave speed measurements can be made for
      different-size apertures and at different focal depths. 

PMID- 24139919
TI  - Contrast-enhanced ultrasound imaging of carotid plaque neo-vascularization:
      accuracy of visual analysis.
AB  - The aim of our study was to evaluate whether neo-vascularization of the carotid
      plaque can be accurately assessed by visual analysis of contrast-enhanced
      ultrasound images and whether these findings correlate with intensity-over-time
      curve analysis (ITC) and histopathology. Patients with >=50% symptomatic or >=60%
      asymptomatic stenosis according to European Carotid Surgery Trial criteria were
      included. Four investigators evaluated contrast enhancement visually (three
      grades), with positive agreement when three or more investigators were unanimous.
      ITC analysis of contrast enhancement was performed in the plaque and in the
      lumen. Histopathology (microvessel density with CD34 + staining) was completed
      when endarterectomy was performed. Visual grading (33 patients, inter-observer
      agreement = 94%) correlated significantly with ITC analysis (p = 0.03).
      Histopathology (n = 19) revealed a larger CD34 + area in patients with grade 1/2
      versus grade 0 (p = 0.03). Visual analysis of neo-vascularization by means of
      contrast-enhanced ultrasound imaging is accurate and reproducible, with
      significant correlations with ITC and histopathology. 

PMID- 24139920
TI  - New insights into mechanisms of sonothrombolysis using ultra-high-speed imaging.
AB  - Thrombotic arterial occlusion is the principal etiology for acute cardiovascular
      syndromes such as stroke, myocardial infarction and unstable angina. Exposing the
      thrombus to ultrasound and microbubbles facilitates thrombus disruption, making
      "sonothrombolysis" a potentially powerful therapeutic strategy for thromboembolic
      diseases. However, optimization of such a strategy, and hence clinical
      translation, is constrained by an incomplete understanding of mechanisms by which
      ultrasound-induced microbubble vibrations disrupt blood clots. We posit that
      previously reported sonothrombolytic efficacy using inertial cavitation regimes
      was due, at least in part, to mechanical clot disruption by oscillating
      microbubbles. To test this hypothesis, we optically characterized lipid
      microbubble interactions with thrombus in the presence of ultrasound using a
      recently developed ultra-high-speed microscopy imaging system to visualize
      microbubble acoustic behaviors at megahertz frame rates. A microscope/acoustic
      stage designed for the system allowed an experimentally created thrombus and
      microbubbles to be insonified at a co-localized acoustic and optical focus during
      synchronized high-speed imaging. Under inertial cavitation conditions, large
      amplitude microbubble oscillations caused thrombus deformation and pitting.
      Acoustic radiation forces (Bjerknes forces) further augmented microbubble
      thrombus interaction. These observations suggest that a direct mechanical effect
      of oscillating lipid microbubbles on an adjacent thrombus may play a role in
      mediating clot disruption in the presence of specific ultrasound conditions. 

PMID- 24139921
TI  - Comparison of perceptual learning of real and virtual line orientations: an event
      related potential study.
AB  - When investigating perceptual learning (PL), most researchers use real figures as
      stimuli, but PL can occur when subjects are trained with virtual stimuli or even
      without any visual stimuli at all. Here, we first demonstrated that virtual lines
      have the same perceptual attributes as real lines by confirming that there is
      also an oblique effect in virtual lines (formed by a pair of circles) in an
      orientation discrimination task. Then, our ERP study showed that orientation
      discrimination learning and its transfer across real and virtual lines were
      associated with more negative parietal-occipital P1-N1 (reduced P1 and enhanced
      N1), which indicated the involvement of high-level stages of visual information
      processing or the involvement of top-down influences. At the same time, the
      specific ERP changes in the frontal ERP components were differently associated
      with real versus virtual line orientation learning. That is, real line learning
      was characterized by an early and short-lasting frontal N1 (120-140 ms)
      reduction, in contrast to a much later, widespread, and long-lasting P150-300
      decrease in virtual line learning. These results contribute to the understanding
      of the neural basis of perceptual learning and the distinction between real and
      virtual stimulus learning.

PMID- 24139922
TI  - Five-year results of laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity, but
      studies reporting long-term results are still rare. The objective of this study
      was to present the 5-year outcome concerning weight loss, modification of co
      morbidities, and late complications. METHODS: This is a retrospective analysis of
      a prospective cohort with a minimal follow-up of 5 years. A total of 68 patients
      underwent LSG either as primary bariatric procedure (n = 41) or as redo operation
      after failed laparoscopic gastric banding (n = 27) between August 2004 and
      December 2007. At the time of LSG, the mean body mass index (BMI) was 43.0 +/-
      8.0 kg/m(2), the mean age 43.1 +/- 10.1 years, and 78% were female. The follow-up
      rate was 100% at 1 year postoperatively, 97% after 2 years, and 91% after 5
      years; the mean follow-up time was 5.9 +/- 0.8 years. RESULTS: The average
      excessive BMI loss was 61.5% +/- 23.4% after 1 year, 61.1% +/- 23.4% after 2
      years, and 57.4% +/- 24.7% after 5 years. Co-morbidities improved considerably; a
      remission of type 2 diabetes could be reached at 85%. The following complications
      were observed: 1 leak (1.5%), 2 incisional hernias (2.9%), and new-onset
      gastroesophageal reflux in 11 patients (16.2%). Reoperation due to insufficient
      weight loss was necessary in 8 patients (11.8%). CONCLUSIONS: LSG was effective
      5.9 years postoperatively with an excessive BMI loss of almost 60% and a
      considerable improvement or even remission of co-morbidities.

PMID- 24139923
TI  - Roux-en-Y gastric bypass compared with aggressive diet and exercise therapy for
      morbidly obese patients awaiting renal transplant: a decision analysis.
AB  - BACKGROUND: The optimal management of morbidly obese patients awaiting renal
      transplant is controversial and unknown. The objective of this study was to
      compare the impact of Roux-en-Y gastric bypass (RYGB) versus diet and exercise on
      the survival of morbidly obese patients with end-stage renal disease awaiting
      renal transplant. METHODS: A decision analytic Markov state transition model was
      designed to simulate the life of morbidly obese patients with end-stage renal
      disease awaiting transplant. Life expectancy after RYGB and after 1 and 2 years
      of diet and exercise was estimated and compared in the framework of 2 clinical
      scenarios in which patients above a body mass index (BMI) of 35 kg/m(2) or above
      a BMI of 40 kg/m(2) were ineligible for transplantation, reflecting the BMI
      restrictions of many transplant centers. In addition to base case analysis (45
      kg/m(2) BMI preintervention), sensitivity analysis of initial BMI was completed.
      Markov model parameters were extracted from the literature. RESULTS: RYGB
      improved survival compared with diet and exercise. Patients who underwent RYGB
      received transplants sooner and in higher frequency. Using 40 kg/m(2) as the
      upper limit for transplant eligibility, base case patients who underwent RYGB
      gained 5.4 years of life, whereas patients who underwent 1 and 2 years of diet
      and exercise gained 1.5 and 2.8 years of life, respectively. Using 35 kg/m(2) as
      the upper limit, RYGB base case patients gained 5.3 years of life, whereas
      patients who underwent 1 and 2 years of diet and exercise gained .7 and 1.5 years
      of life, respectively. CONCLUSIONS: In morbidly obese patients with end-stage
      renal disease, RYGB may be more effective than optimistic weight loss outcomes
      after diet and exercise, thereby improving access to renal transplantation.

PMID- 24139924
TI  - The partial underlay preperitoneal with panniculectomy repair for incisional
      abdominal hernia in the morbidly obese.
AB  - BACKGROUND: Because of high frequency, high morbidity, and difficulty of repair,
      incisional hernias in obese patients represent a particularly vexing and common
      problem for surgeons. The objective of this study was to describe a highly
      selective technique for incisional hernia repair with panniculectomy in the
      morbidly obese. We also describe perioperative characteristics and preliminary
      outcomes for a limited series of patients who underwent this procedure. METHODS:
      We performed a preperitoneal partial mesh underlay with a panniculectomy (PUPP)
      on 10 patients with incisional hernias and a body mass index (BMI)>40 kg/m(2).
      The hernia repair was performed by a general surgery team, and the panniculectomy
      was performed by a plastic surgery team. We retrospectively analyzed
      perioperative variables for each patient. Phone interviews were conducted to
      obtain follow-up. RESULTS: Mean patient age was 53 years (range 32-75 yr) with
      mean BMI of 46 kg/m(2) (range 41-60 kg/m(2)). Patients had a history of 3.4
      average prior abdominal operations, and a median of 3 prior hernia repairs. The
      average operative time was 371 minutes with a mean estimated blood loss of 162
      ccs. Three patients experienced a minor wound complication. There were no major
      wound complications, and the 30-day mortality rate was zero. At a median and
      average follow-up time of 805 and 345 days, respectively, one patient developed a
      hernia recurrence. Patients were satisfied with their appearance and the hernia
      repair, with mean satisfaction scores of 4.3 and 4.9 out of 5 (very satisfied),
      respectively. CONCLUSION: The PUPP hernia repair is a viable option for
      incisional herniorrhaphy and concurrent panniculectomy in the morbidly obese.

PMID- 24139925
TI  - Comment on: The effect of socioeconomic and individual factors on acceptance
      levels of bariatric surgery among Chinese patients.

PMID- 24139926
TI  - Combination antibiotic therapy versus monotherapy for Pseudomonas aeruginosa
      bacteraemia: a meta-analysis of retrospective and prospective studies.
AB  - The choice of antibiotic monotherapy or combination therapy to treat Pseudomonas
      aeruginosa bacteraemia is controversial. The aim of this review was to compare
      both types of therapy to determine which delivers the best outcome for P.
      aeruginosa bacteraemia. We systematically searched electronic bibliographic
      databases, including PubMed, Ovid EMBASE and The Cochrane Library, for clinical
      studies that compared combination therapy with monotherapy in the treatment of P.
      aeruginosa bacteraemia. Eligible articles were analysed using Stata((r))/SE
      software v.12.0. Stratification analysis was conducted by study design and
      treatment type. Publication bias was assessed using Begg's funnel plot and
      Egger's test. Ten studies (eight retrospective and two prospective) involving
      1239 patients were analysed. We found no difference between combination therapy
      and monotherapy when the data were combined (odds ratio = 0.89, 95% confidence
      interval 0.57-1.40; P = 0.614) or when data were analysed in subgroups. Neither
      combination therapy nor monotherapy treatment appears to have a significant
      effect on mortality rates in patients with P. aeruginosa bacteraemia. Further
      studies evaluating the effects of combination therapy or monotherapy in more
      specialised cases, such as when encountering a multidrug-resistant organism, are
      necessary.

PMID- 24139927
TI  - Editorial for the MCE special issue on "Novel endocrine mechanisms in the
      regulation of reproduction".

PMID- 24139928
TI  - Transcatheter aortic valve implantation reduces sympathetic activity and
      normalizes arterial spontaneous baroreflex in patients with aortic stenosis.
AB  - OBJECTIVES: This study sought to measure muscle sympathetic nerve activity (MSNA)
      in patients with aortic stenosis (AS) before and after transcatheter aortic valve
      implantation (TAVI) and to compare MSNA with that of control patients.
      BACKGROUND: TAVI is an emerging therapeutic option in patients with severe AS at
      high risk of open heart surgery. Whether patients with AS have increased
      sympathetic activity remains to be established, and the effects of TAVI on the
      sympathetic nervous system are also unknown. METHODS: We prospectively enrolled
      14 patients with severe symptomatic AS treated by TAVI. Fourteen control patients
      matched for age, body mass index, and unscathed of AS were also included. All
      patients underwent MSNA and arterial baroreflex gain assessment at baseline and 1
      week after TAVI for AS patients. RESULTS: Patients with AS had lower blood
      pressure (BP) levels, a significant increase in MSNA (61.0 +/- 1.7 burst/min vs.
      55.4 +/- 1.4 burst/min; p < 0.05), and a decrease in arterial baroreflex gain
      (2.13 +/- 0.14% burst/mm Hg vs. 3.32 +/- 0.19% burst/mm Hg; p < 0.01) compared
      with matched control patients. The TAVI procedures induced an increase in BP
      associated with a significant decrease in MSNA (from 61.0 +/- 1.7 burst/min to
      54.1 +/- 1.0 burst/min; p < 0.01) and was associated with a significant increase
      in arterial baroreflex gain (from 2.13 +/- 0.14% burst/mm Hg to 3.49 +/- 0.33%
      burst/mm Hg; p < 0.01). CONCLUSIONS: We report for the first time, through direct
      measurement of nerve activity, that patients with AS have increased sympathetic
      nervous system activity associated with a decrease in sympathetic baroreflex gain
      and that TAVI normalizes these parameters. This study provides evidence of a new
      beneficial effect of TAVI, namely, normalization of sympathetic nervous system
      hyperactivity.

PMID- 24139929
TI  - Device closure of patent foramen ovale versus medical therapy in cryptogenic
      stroke: a systematic review and meta-analysis.
AB  - OBJECTIVES: This study sought to perform a meta-analysis of randomized controlled
      trials comparing device closure with medical therapy in the prevention of
      recurrent neurological events in patients with cryptogenic stroke and patent
      foramen ovale. BACKGROUND: The optimal strategy for secondary prevention of
      cryptogenic stroke with a patent foramen ovale is unclear. METHODS: Several
      databases were searched from their inception to March 2013, which yielded 3
      eligible studies. The results were pooled as per the different patient
      populations defined in the studies:-intention-to-treat, per-protocol, and as
      treated cohorts. A generic inverse method was used based on time-to-event
      outcomes in a fixed-effect model. A supplementary analysis pooled the results
      from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing
      PFO Closure to Established Current Standard of Care Treatment] and PC Trial
      [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of
      Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic
      Embolism]) as a similar device was used in them. RESULTS: Our meta-analysis
      yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44
      to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to
      0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95,
      I(2) = 38%) in the as-treated cohort, showing beneficial effects of device
      closure. The results became more robust with pooled results from RESPECT and the
      PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01,
      I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to
      0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated
      populations, respectively. CONCLUSIONS: Our meta-analysis suggests that PFO
      closure is beneficial as compared to medical therapy in the prevention of
      recurrent neurological events. This meta-analysis helps to further strengthen the
      role of device closure in cryptogenic stroke.

PMID- 24139930
TI  - A randomized comparison of the transradial and transfemoral approaches for
      coronary artery bypass graft angiography and intervention: the RADIAL-CABG Trial
      (RADIAL Versus Femoral Access for Coronary Artery Bypass Graft Angiography and
      Intervention).
AB  - OBJECTIVES: This study sought to compare and contrast use and radiation exposure
      using radial versus femoral access during cardiac catheterization of patients who
      had previously undergone coronary artery bypass graft (CABG) surgery. BACKGROUND:
      Limited information is available on the relative merits of radial compared with
      femoral access for cardiac catheterization in patients who had previously
      undergone CABG surgery. METHODS: Consecutive patients (N = 128) having previously
      undergone CABG surgery and referred for cardiac catheterization were randomized
      to radial or femoral access. The primary study endpoint was contrast volume.
      Secondary endpoints included fluoroscopy time, procedure time, patient and
      operator radiation exposure, vascular complications, and major adverse cardiac
      events. Analyses were by intention-to-treat. RESULTS: Compared with femoral
      access, diagnostic coronary angiography via radial access was associated with a
      higher mean contrast volume (142 +/- 39 ml vs. 171 +/- 72 ml, p < 0.01), longer
      procedure time (21.9 +/- 6.8 min vs. 34.2 +/- 14.7 min, p < 0.01), greater
      patient air kerma (kinetic energy released per unit mass) radiation exposure
      (1.08 +/- 0.54 Gy vs. 1.29 +/- 0.67 Gy, p = 0.06), and higher operator radiation
      dose (first operator: 1.3 +/- 1.0 mrem vs. 2.6 +/- 1.7 mrem, p < 0.01; second
      operator 0.8 +/- 1.1 mrem vs. 1.8 +/- 2.1 mrem, p = 0.01). Fewer patients
      underwent ad hoc percutaneous coronary intervention (PCI) in the radial group
      (37.5% vs. 46.9%, p = 0.28) and radial PCI procedures were less complex. The
      incidences of the primary and secondary endpoints was similar with femoral and
      radial access among PCI patients. Access crossover was higher in the radial group
      (17.2% vs. 0.0%, p < 0.01) and vascular access site complications were similar in
      both groups (3.1%). CONCLUSIONS: In patients who had previously undergone CABG
      surgery, transradial diagnostic coronary angiography was associated with greater
      contrast use, longer procedure time, and greater access crossover and operator
      radiation exposure compared with transfemoral angiography. (RADIAL Versus Femoral
      Access for Coronary Artery Bypass Graft Angiography and Intervention [RADIAL
      CABG] Trial; NCT01446263).

PMID- 24139931
TI  - Fluoroscopic guide to an ideal implant position for Sapien XT and CoreValve
      during a valve-in-valve procedure.
AB  - OBJECTIVES: This study sought to provide a guide to the fluoroscopic appearances
      of various valve-in-valve (VIV) combinations by deploying a transcatheter heart
      valve (THV) within a degenerated surgical heart valve (SHV) in an ideal position.
      BACKGROUND: VIV procedures are being increasingly performed with substantial
      experience acquired in treating degenerated SHV in the aortic position with
      Sapien/Sapien XT (Edwards Lifesciences Ltd., Irvine, California) and
      CoreValve/Evolute (Medtronic Inc., Minneapolis, Minnesota) valves. Although less
      invasive than conventional surgery, securing the THV in an optimal position
      within the SHV determines the success of this novel treatment. METHODS: For VIV
      implantation, we selected appropriate Sapien XT and CoreValve/Evolute sizes
      depending on the internal diameter of the SHV. Implantation was performed in
      vitro. In case of the Sapien XT valve, it was deployed 4 to 5 mm below the sewing
      ring of the SHV, whereas the CoreValve/Evolute was deployed 5 mm below the level
      of the sewing ring. Photographs and fluoroscopic images of the various VIV
      combinations were obtained in side profile to study the ideal position and end-on
      profile to study the circularity of the THV. RESULTS: Fluoroscopic images
      obtained in side profile highlighted the differences in various VIV combinations,
      as all SHV are unique in their fluoroscopic appearances. Also, all THV implants
      in various VIV combinations achieved a nearly circular shape. CONCLUSIONS: To
      achieve an optimal result when considering VIV, it is important to be familiar
      with the structure and fluoroscopic appearances of the failed SHV, the THV used,
      and their combination.

PMID- 24139932
TI  - A next-generation bioresorbable coronary scaffold system: from bench to first
      clinical evaluation: 6- and 12-month clinical and multimodality imaging results.
AB  - OBJECTIVES: This study sought to perform clinical and imaging assessments of the
      DESolve Bioresorbable Coronary Scaffold (BCS). BACKGROUND: BCS, which is drug
      eluting, may have potential advantages compared with conventional metallic drug
      eluting stents. The DESolve system, designed to provide vessel support and
      neointimal suppression, combines a poly-l-lactic acid-based scaffold with the
      antiproliferative myolimus. METHODS: The DESolve First-in-Man (a non-randomized,
      consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable
      coronary stent in the treatment of patients with de novo native coronary artery
      lesions) trial was a prospective multicenter study enrolling 16 patients eligible
      for treatment. The principal safety endpoint was a composite of cardiac death,
      myocardial infarction, and clinically indicated target lesion revascularization.
      The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by
      quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound
      (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline
      and 6 months; multislice computed tomography (MSCT) was performed at 12 months.
      RESULTS: Acute procedural success was achieved in 15 of 15 patients receiving a
      study scaffold. At 12 months, there was no scaffold thrombosis and no major
      adverse cardiac events directly attributable to the scaffold. At 6 months, in
      scaffold LLL (by QCA) was 0.19 +/- 0.19 mm; neointimal volume (by IVUS) was 7.19
      +/- 3.56%, with no evidence of scaffold recoil or late malapposition. Findings
      were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 +/-
      0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency. CONCLUSIONS:
      This study demonstrated the feasibility and efficacy of the DESolve BCS. Results
      showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic
      recoil, and maintenance of lumen patency at 12 months prompt further study.
      (DESolve First-in-Man; EudraCT number 2011-000027-32).

PMID- 24139933
TI  - Risk score, causes, and clinical impact of failure of transradial approach for
      percutaneous coronary interventions.
AB  - OBJECTIVES: To study the causes of and to develop a risk score for failure of
      transradial approach (TRA) for percutaneous coronary intervention (PCI).
      BACKGROUND: TRA-PCI failure has been reported in 5% to 10% of cases. METHODS: TRA
      PCI failure was categorized as primary (clinical reasons) or crossover failure.
      Multivariate analysis was performed to determine independent predictors of TRA
      PCI failure, and an integer risk score was developed. RESULTS: From January to
      June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas
      45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30
      (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery
      occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic
      shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture
      in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%);
      subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%)
      patients. Female sex (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.95 to
      5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63
      to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p =
      0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0
      to 7 predicted a TRA-PCI failure rate from 2% to 80%. CONCLUSIONS: In a high
      volume radial center, 2.7% of patients undergoing PCI are excluded from initial
      TRA on clinical grounds, whereas crossover to femoral approach is required in
      only 1.8% of the cases. A new simple clinical risk score is developed to predict
      TRA-PCI failure.

PMID- 24139934
TI  - Effect of ovarian tissue vitrification method on mice preantral follicular
      development and gene expression.
AB  - Vitrification is considered a viable method for cryopreservation of ovarian
      tissue and selection of methods that minimize follicular damage is important. The
      objective of the present study was to evaluate the effects of two vitrification
      methods on ovarian tissue morphology, preantral follicles survival rate during in
      vitro culture, and relative expression of genes associated with oocyte maturation
      and cumulus expansion. Ovaries from 12-day-old mice were vitrified in media
      containing ethylene glycol, dimethyl sulphoxide, and sucrose. Before plunging in
      liquid nitrogen, ovaries were first loaded into an acupuncture needle (needle
      immersion vitrification [NIV]) or placed on a cold steel surface for 10 to 20
      seconds (solid surface vitrification [SSV]). The integrity of the ovarian tissue
      was well-preserved after vitrification and was similar controls. Follicle
      viability in the SSV group was lower (P < 0.05) than in the control group after 6
      days of culture and the NIV group after 10 day of culture. Follicle viability
      after 12 day of culture was 92.8%, 82.1%, and 58.4% in control, NIV, and SSV
      groups, respectively. Bmp15, Gdf9, BmprII, Alk6, Alk5, Has2, and Ptgs2 gene
      expression patterns were similar among groups. However, the level of gene
      expression in the vitrification groups during Days 6 to 10 were higher compared
      with the control group. In conclusion, ovarian tissue morphologic integrity was
      well-preserved, regardless of the vitrification method. Vitrification using the
      needle immersion method resulted in greater follicular survival after 12 day of
      culture than the SSV method. Gene expression patterns during culture did not seem
      to explain the reduced survival rate observed in the solid surface group.

PMID- 24139935
TI  - Resynchronization with unknown pregnancy status using progestin-based timed
      artificial insemination protocol in beef cattle.
AB  - Two experiments were designed to evaluate the use of resynchronization (RESYNCH)
      protocols using a progestin-based timed artificial insemination (TAI) protocol in
      beef cattle. In experiment 1, 475 cyclic Nelore heifers were resynchronized 22
      days after the first TAI using two different inducers of new follicular wave
      emergence (estradiol benzoate [EB; n = 241] or GnRH [n = 234]) with the insertion
      of a norgestomet ear implant. At ear implant removal (7 days later), a pregnancy
      test was performed, and nonpregnant heifers received a dose of prostaglandin plus
      0.5 mg of estradiol cypionate, with a timed insemination 48 hours later. The
      pregnancy rate after the first TAI was similar (P = 0.97) between treatments (EB
      [41.9%] vs. GnRH [41.5%]). However, EB-treated heifers (49.3%) had a greater (P =
      0.04) pregnancy per AI (P/AI) after the resynchronization than the GnRH-treated
      heifers (37.2%). In experiment 2, the pregnancy loss in 664 zebu females (344
      nonlactating cows and 320 cyclic heifers) between 30 and 60 days after
      resynchronization was evaluated. Females were randomly assigned to one of two
      groups (RESYNCH 22 days after the first TAI [n = 317] or submitted only to
      natural mating [NM; n = 347]). Females from the NM group were maintained with
      bulls from 15 to 30 days after the first TAI. The RESYNC-treated females were
      resynchronized 22 days after the first TAI using 1 mg of EB on the first day of
      the resynchronization, similar to experiment 1. No difference was found in P/AI
      (NM [57.1%] vs. RESYNC [61.5%]; P = 0.32) or pregnancy loss (NM [2.0%] vs. RESYNC
      [4.1%]; P = 0.21) after the first TAI. Moreover, the overall P/AI after the
      RESYNCH protocol was 47.5%. Thus, the administration of 1 mg of EB on day 22
      after the first TAI, when the pregnancy status was undetermined, promotes a
      higher P/AI in the resynchronized TAI than the use of GnRH. Also, the
      administration of 1 mg of EB 22 days after the TAI did not affect the
      preestablished pregnancy. 

PMID- 24139936
TI  - The effect of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha
      on estradiol-17beta release in the myometrium: the in vitro study on the pig
      model.
AB  - Estradiol-17beta (E2) is a potent regulator of early pregnancy and the estrous
      cycle in pigs. Production of E2 occurs in the porcine myometrium, but the factors
      involved in its regulation are unknown. In this in vitro study, it was
      investigated whether interleukin (IL)-1beta, IL-6, and tumor necrosis factor
      (TNF)-alpha affect the release of E2 from the porcine myometrium on Days 10 to
      11, 12 to 13, and 15 to 16 of pregnancy and the estrous cycle. The expression of
      the cytochrome P450 family 19 (CYP19) gene and the presence of the aromatase
      cytochrome P450 protein in the myometrium confirmed the ability of the tissue to
      produce E2. In gravid pigs, the expression of IL1RI mRNA and IL6R mRNA was
      markedly increased on Days 15 to 16 of gestation, whereas TNFRI mRNA was
      increased on Days 10 to 11 of gestation. In cyclic pigs, the expression of
      myometrial IL1RI mRNA did not differ among the studied days, although the
      expression of IL6R and TNFRI mRNAs was increased on Days 15 to 16. In gravid
      pigs, IL-1beta, IL-6, and TNF-alpha increased myometrial E2 secretion on Days 15
      to 16 but did not affect E2 release on Days 10 to 11 and 12 to 13 of pregnancy.
      In cyclic pigs, IL-1beta, IL-6, and TNF-alpha did not increase myometrial E2
      release. In conclusion, IL-1beta, IL-6, and TNF-alpha affected myometrial E2
      release in a manner that is dependent on the physiologic status of the female.
      The porcine myometrium expresses IL1RI, IL6R, and TNFRI genes and is the target
      tissue for IL-1beta, IL-6, and TNF-alpha. In gravid pigs, IL-1beta, IL-6, and TNF
      alpha may increase myometrial release of E2 in vitro specifically on Days 15 to
      16 of pregnancy. These findings may be of interest to researchers using pigs as
      an animal model for fetal programming.

PMID- 24139937
TI  - An analysis of the inpatient charge and length of stay for patients with joint
      diseases in Korea: specialty versus small general hospitals.
AB  - In 2011, the Korean government designated hospitals with certain structural
      characteristics as specialty hospitals. This study compared the inpatient charges
      and length of stay of patients with joint diseases treated at these specialty
      hospitals with those of patients treated at small general hospitals. In addition,
      the study investigated whether the designation of certain hospitals as specialty
      hospitals had an effect on inpatient charges and length of stay. Multi-level
      models were used to perform regression analyses on inpatient claims data
      (N=268,809) for 2010-2012 because of the hierarchical structure of the data. The
      inpatient charge at specialty hospitals was 19% greater than that at small
      general hospitals, but the length of stay was 21% shorter. After adjusting for
      patient and hospital level confounders, specialty hospitals had a higher
      inpatient charge (34.6%) and a reduced length of stay (31.7%). However, the
      effect of specialty hospital designation on inpatient charge (2.7% higher) and
      length of stay (2.3% longer) was relatively smaller. Among the patient
      characteristics, female gender, age, and severity of illness were positively
      associated with inpatient charge and length of stay. In terms of location,
      hospitals in metropolitan area had higher inpatient charges (5.5%), but much
      shorter length of stay (-14%). Several structural factors, such as occupancy
      rate, bed size, number of outpatients and nurses were positively associated with
      both inpatient charges and length of stay. However, number of specialists was
      positively associated with inpatient charges, but negatively associated with
      length of stay. In sum, this study found that specialty hospitals treating joint
      diseases tend to incur higher charges but produce shorter length of stay,
      compared to their counterparts. Specialty hospitals' overcharging behaviors,
      although shorter length of stay, suggest that policy makers could introduce
      bundled payments for the joint procedures. To promote a successful specialty
      hospital system, a broader discussion and investigation that includes quality
      measures as well as real cost of care should be initiated. 

PMID- 24139938
TI  - The case for amniocentesis for fetal lung maturity in late-preterm and early-term
      gestations.

PMID- 24139939
TI  - Cytokines affecting CD4(+) T regulatory cells in transplant tolerance.
      Interleukin-4 does not maintain alloantigen specific CD4(+)CD25(+) Treg.
AB  - IL-4 is thought to promote induction of transplantation tolerance and alloantigen
      specific CD4(+)CD25(+) T regulatory cells (Treg). This study examined the effect
      of IL-4 on the induction and maintenance of the CD4(+) T regulatory cells (Treg)
      that mediate transplantation tolerance. Tolerance was induced in DA rats with PVG
      heterotopic cardiac allografts by a short course of cyclosporine. Naive and
      tolerant lymphocytes, including the CD4(+) and CD4(+)CD25(+) T cell subsets, were
      assayed in mixed lymphocyte cultures with or without recombinant (r)IL-4 or other
      cytokines. The proliferation, cell surface and cytokine phenotype of these cells
      was examined, as was their capacity to adoptively transfer tolerance. rIL-4
      enhanced the proliferation of naive and tolerant lymphoid cells, including CD4(+)
      and CD4(+)CD25(+) T cells, but this was not alloantigen specific. Naive or
      tolerant CD4(+) T cells cultured with rIL-4 and donor PVG antigen effected rapid
      graft rejection, even though before culture tolerant CD4(+) T cells transferred
      antigen-specific tolerance. These rIL-4 cultured CD4(+) T cells had a phenotype
      consistent with activated CD4(+)CD25(+)FoxP3(-) Th2 cells. While naive natural
      CD4(+)CD25(+) T cells (nTreg) cultured with alloantigen and rIL-4 had enhanced
      proliferation and capacity to suppress rejection in vivo, the culture of tolerant
      CD4(+)CD25(+) T cells with alloantigen and rIL-4 could not sustain their
      proliferation against specific donor, nor their capacity to transfer tolerance to
      specific donor allograft. Thus, IL-4 promotes both regulatory and effector T
      cells early in the immune response, but once alloimmune tolerance is established,
      IL-4 promoted the activation of effector cells to mediate rejection and did not
      support alloantigen-specific Treg that could transfer specific tolerance. 

PMID- 24139940
TI  - Design and synthesis of silicon-containing tubulin polymerization inhibitors:
      replacement of the ethylene moiety of combretastatin A-4 with a silicon linker.
AB  - Silicon-containing combretastatin analogs were designed, synthesized and
      evaluated for stability and biological activities. Among them, compound 31
      exhibited strong tubulin polymerization-inhibitory activity and very potent tumor
      cell growth-inhibitory activity (IC50=0.007 MUM) in MCF-7 cell proliferation
      assay. This compound also potently inhibited [(3)H]colchicine binding (90.7%
      inhibition at 3 MUM). These activities were comparable to those of combretastatin
      A-4 (CA-4) (1). In addition, compound 31 was physico-chemically more stable than
      1. These results suggest that a silicon linker can act as a bioisoster of a cis
      carbon-carbon double bond.

PMID- 24139941
TI  - 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs: a novel cluster of
      antimalarials targeting the liver stage of Plasmodium falciparum.
AB  - Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a
      complete cure of malaria requires intervention at various stages in the
      development of the parasite within the host. There are only a few antimalarials
      that target the liver stage of the Plasmodium species which is an essential part
      of the life cycle of the malarial parasite. We report a series of antimalarial
      3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1-5, a number of
      which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive
      D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting
      the liver stage development of the malarial life cycle. The compounds 2b (IC50:
      165 ng/mL), 3b (IC50: 186 ng/mL), 5c (IC50: 159 ng/mL) and 5d (IC50: 93.5 ng/mL)
      emerged as lead molecules that inhibit liver stage Plasmodium berghei and are
      significantly more potent than chloroquine (IC50: >2000 ng/mL) and mefloquine
      (IC50: >2000 ng/mL) in this screen. All the compounds that showed potent
      inhibitory activity against the P. berghei liver stage were nontoxic to human
      HepG2 liver cells (IC50: >2000 ng/mL). The compounds 5a and 5b exhibit comparable
      metabolic stability as chloroquine and mefloquine in human plasma and the most
      potent compound 5d demonstrated suitable permeability characteristics using the
      MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4
      piperidones as novel antimalarials for further drug development.

PMID- 24139942
TI  - Determinants of laparoscopic donor nephrectomy outcomes.
AB  - BACKGROUND: Pure laparoscopic donor nephrectomy (LDN) is a unique intervention
      because it carries known risks and complications, yet carries no direct benefit
      to the donor. Therefore, it is critical to continually examine and improve
      quality of care. OBJECTIVE: To identify factors affecting LDN outcomes and
      complications. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of
      prospectively collected data for 1204 consecutive LDNs performed from March 2000
      through August 2012. INTERVENTION: LDN performed at an academic training center.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable regression, we
      assessed the effect of age, sex, body mass index (BMI), laterality, and vascular
      variation on operative time, estimated blood loss (EBL), complications, and
      length of stay. RESULTS AND LIMITATIONS: The following variables were associated
      with longer operative time (data given as parameter estimate plus or minus the
      standard error): female sex (9.09 +/- 2.43; p<0.001), higher BMI (1.03 +/- 0.32;
      p=0.001), two (7.87 +/- 2.70; p=0.004) and three or more (22.45 +/- 7.13;
      p=0.002) versus one renal artery, and early renal arterial branching (5.67 +/-
      2.82; p=0.045), while early renal arterial branching (7.81 +/- 3.85; p=0.043) was
      associated with higher EBL. Overall, 8.2% of LDNs experienced complications, and
      by modified Clavien classification, 74 (5.9%) were grade 1, 13 (1.1%) were grade
      2a, 10 (0.8%) were grade 2b, and 2 (0.2%) were grade 2c. There were no grade 3 or
      4 complications. Three or more renal arteries (odds ratio [OR]: 2.74; 95% CI,
      1.05-7.16; p=0.04) and late renal vein confluence (OR: 2.42; 95% CI, 1.50-3.91;
      p=0.0003) were associated with more complications. Finally, we did not find an
      association of the independent variables with length of stay. A limitation is
      that warm ischemia time was not assessed. CONCLUSIONS: In our series, renal
      vascular variation prolonged operative time and was associated with more
      complications. While complicated donor anatomy is not a contraindication of LDN,
      surgical decision-making should take into consideration these results.

PMID- 24139943
TI  - Surface modification via wet chemical etching of single-crystalline silicon for
      photovoltaic application.
AB  - The potential of solar cells have not been fully tapped due to the lack of energy
      conversion efficiency. There are three important mechanisms in producing high
      efficiency cells to harvest solar energy; reduction of light reflectance,
      enhancement of light trapping in the cell and increment of light absorption. The
      current work represent studies conducted in surface modification of single
      crystalline silicon solar cells using wet chemical etching techniques. Two
      etching types are applied; alkaline etching (KOH:IPA:DI) and acidic etching
      (HF:HNO3:DI). The alkaline solution resulted in anisotropic profile that leads to
      the formation of inverted pyramids. While acidic solution formed circular craters
      along the front surface of silicon wafer. This surface modification will leads to
      the reduction of light reflectance via texturizing the surface and thereby
      increases the short circuit current and conversion rate of the solar cells. 

PMID- 24139944
TI  - Targeting tumor micro-environment for design and development of novel anti
      angiogenic agents arresting tumor growth.
AB  - Angiogenesis: a process of generation of new blood vessels has been proved to be
      necessary for sustained tumor growth and cancer progression. Inhibiting
      angiogenesis pathway has long been remained a significant hope for the
      development of novel, effective and target orientated antitumor agents arresting
      the tumor proliferation and metastasis. The process of neoangiogenesis as a
      biological process is regulated by several pro- and anti-angiogenic factors,
      especially vascular endothelial growth factor, fibroblast growth factor,
      epidermal growth factor, hypoxia inducible factor 1 and transforming growth
      factor. Every endothelial cell destined for vessel formation is equipped with
      receptors for these angiogenic peptides. Moreover, numerous other angiogenic
      cytokines such as platelet derived growth factor (PGDF), placenta growth factor
      (PGF), nerve growth factor (NGF), stem-cell factor (SCF), and interleukins-2, 4,
      6 etc. These molecular players performs critical role in regulating the
      angiogenic switch. Couple of decade's research in molecular aspects of tumor
      biology has unraveled numerous structural and functional mysteries of these
      angiogenic peptides. In present article, a detailed update on the functional and
      structural peculiarities of the various angiogenic peptides is described focusing
      on structural opportunities made available that has potential to be used to
      modulate function of these angiogenic peptides in developing therapeutic agents
      targeting neoplastic angiogenesis. The data may be useful in the mainstream of
      developing novel anticancer agents targeting tumor angiogenesis. We also discuss
      major therapeutic agents that are currently used in angiogenesis associated
      therapies as well as those are subject of active research or are in clinical
      trials. 

PMID- 24139945
TI  - Elucidating the metabolic regulation of liver regeneration.
AB  - The regenerative capability of liver is well known, and the mechanisms that
      regulate liver regeneration are extensively studied. Such analyses have defined
      general principles that govern the hepatic regenerative response and implicated
      specific extracellular and intracellular signals as regulated during and
      essential for normal liver regeneration. Nevertheless, the most proximal events
      that stimulate liver regeneration and the distal signals that terminate this
      process remain incompletely understood. Recent data suggest that the metabolic
      response to hepatic insufficiency might be the proximal signal that initiates
      regenerative hepatocellular proliferation. This review provides an overview of
      the data in support of a metabolic model of liver regeneration and reflects on
      the clinical implications and areas for further study suggested by these
      findings. 

PMID- 24139947
TI  - Immunohistological analysis of neurturin and its receptors in human cochlea.
AB  - OBJECTIVE: Difficulties in obtaining properly preserved human cochlea have been a
      major obstacle to in vitro study of this deeply located and hard bone-fortressed
      hearing organ. Our study aimed at investigating GDNF family ligands (GFLs) and
      their receptors in the human cochleae that were surgically obtained during a
      transcochlear approach dealing with life-threatening, intra-cranial meningiomas.
      METHODS: The specimens were properly fixed with 4% paraformaldehyde in the
      operating room. By using immunohistochemical techniques, distribution of GDNF,
      Neurturin (NTN, one member of GFLs), as well as cRet, GFRalpha-1 and GFRalpha-2
      receptors in the human cochleae was investigated. Five cochleae from five adult
      patients were processed for the study. The patients had normal hearing threshold
      before operation. RESULTS: cRet receptor immunoreactivity was seen in the spiral
      ganglion neurons, mainly inside the cell bodies but rarely in the nerve fibers
      and not in the organ of Corti. Immunolabeling for GFRalpha-1 and GFRalpha-2
      receptors was identified mainly in the cell bodies of the spiral neurons than in
      the nerve fibers. In the organ of Corti, GFRalpha-1 immunostaining could be
      demonstrated in the Deiters' cells, Hensen cells, inner pillar cells, and weakly
      in the inner hair cells but not in the outer hair cells; no structures in the
      organ of Corti were labeled with GFRalpha-2 receptor antibody. NTN immunostaining
      was found in the supporting cells of organ of Corti, including Deiters' cells,
      Hensen cells as well as Claudius' cells. In the spiral ganglia, NTN
      immunostaining was seen in both the cell bodies and the nerve fibers of neurons.
      GDNF immunoreactivity was not revealed in human cochlea. CONCLUSION: Surgically
      obtained human cochleae were properly fixed and underwent immunohistochemical
      investigation of neurotrophic elements. NTN and its receptors discovered in
      current study can be responsible for the unique neuronal survival properties in
      human spiral ganglion (hSG); a prerequisite for the function of cochlear
      implants.

PMID- 24139946
TI  - Is cancer a metabolic disease?
AB  - Although cancer has historically been viewed as a disorder of proliferation,
      recent evidence has suggested that it should also be considered a metabolic
      disease. Growing tumors rewire their metabolic programs to meet and even exceed
      the bioenergetic and biosynthetic demands of continuous cell growth. The
      metabolic profile observed in cancer cells often includes increased consumption
      of glucose and glutamine, increased glycolysis, changes in the use of metabolic
      enzyme isoforms, and increased secretion of lactate. Oncogenes and tumor
      suppressors have been discovered to have roles in cancer-associated changes in
      metabolism as well. The metabolic profile of tumor cells has been suggested to
      reflect the rapid proliferative rate. Cancer-associated metabolic changes may
      also reveal the importance of protection against reactive oxygen species or a
      role for secreted lactate in the tumor microenvironment. This article reviews
      recent research in the field of cancer metabolism, raising the following
      questions: Why do cancer cells shift their metabolism in this way? Are the
      changes in metabolism in cancer cells a consequence of the changes in
      proliferation or a driver of cancer progression? Can cancer metabolism be
      targeted to benefit patients? 

PMID- 24139948
TI  - Oral manifestations and blood profile in patients with thalassemia trait.
AB  - BACKGROUND/PURPOSE: Patients with thalassemia trait (TT) may have anemia. This
      study evaluated whether TT patients had specific oral manifestations and a
      particular blood profile compared with normal individuals. METHODS: The oral
      manifestations and mean red blood cell count, corpuscular cell volume, red blood
      cell distribution width, Mentzer index, and Green and King index as well as blood
      concentrations of hemoglobin, iron, total iron binding capacity, vitamin B12,
      folic acid, and homocysteine in 65 TT patients and in 130 age- and sex-matched
      healthy controls were measured and compared. RESULTS: TT patients had
      significantly higher frequencies of all oral manifestations than healthy controls
      (p < 0.001 for all), in which burning sensation of oral mucosa (90.8%), lingual
      varicosity (90.8%), dry mouth (72.3%), atrophic glossitis (32.3%), and numbness
      of the oral mucosa (30.8%) were the five leading oral manifestations for TT
      patients. Moreover, TT patients had significantly lower mean hemoglobin level,
      corpuscular cell volume, Mentzer index, and Green and King index (p < 0.001 for
      all) as well as significantly higher mean red blood cell count and red blood cell
      distribution width (p < 0.001 for both) than healthy controls. However, no
      significant difference in the mean blood iron, total iron binding capacity,
      vitamin B12, folic acid, or homocysteine levels was discovered between 65 TT
      patients and 130 healthy controls. CONCLUSION: TT patients have specific oral
      manifestations and a particular blood profile compared to normal individuals.

PMID- 24139949
TI  - Dissociations between faces and words: comment on Behrmann and Plaut.

PMID- 24139950
TI  - Cortical dynamics revisited.
AB  - Recent discoveries on the organisation of the cortical connectome together with
      novel data on the dynamics of neuronal interactions require an extension of
      classical concepts on information processing in the cerebral cortex. These new
      insights justify considering the brain as a complex, self-organised system with
      nonlinear dynamics in which principles of distributed, parallel processing
      coexist with serial operations within highly interconnected networks. The
      observed dynamics suggest that cortical networks are capable of providing an
      extremely high-dimensional state space in which a large amount of evolutionary
      and ontogenetically acquired information can coexist and be accessible to rapid
      parallel search. 

PMID- 24139951
TI  - Diagnostic yield of coronary angiography in patients with acute chest pain: role
      of noninvasive test.
AB  - OBJECTIVES: This study investigated the diagnostic yield of invasive coronary
      angiography (CAG) and the impact of noninvasive test (NIV) in patients presented
      to emergency department (ED) with acute chest pain. METHODS: Patients 50 years or
      older who visited ED with acute chest pain and underwent CAG were identified
      retrospectively. Those with ischemic electrocardiogram, elevated cardiac enzyme,
      known coronary artery disease (CAD), history of cardiac surgery, renal failure,
      or allergy to radiocontrast were excluded. Diagnostic yields of CAG to detect
      significant CAD or differentiate the need for revascularization were analyzed
      according to whether NIV was performed and its result. RESULTS: Among the total
      375 consecutive patients, significant CAD was observed in 244 (65.1%). Diagnostic
      yields of CAG were higher in patients who underwent NIV before CAG, but the
      discriminative effect was modest (59.7% vs 70.7% [P = .026] for detection of CAD;
      45.0% vs 50.5% [P = .285] for revascularization). Positive results of NIV were
      significantly associated with the presence of CAD and the need for
      revascularization, when compared with patients without NIV or patients with
      negative results (P < .001, respectively). CONCLUSION: The diagnostic yield of
      CAG was only 65% in low- to intermediate-risk ED patients with acute chest pain.
      Performing of NIV provided only modest improvement in diagnostic yield of CAG.
      The unexpectedly low diagnostic yield might be attributable to the underuse of
      NIV and misinterpretation of physicians. We suggest the use of NIV as a
      gatekeeper to discriminate patients who require CAG and/or revascularization, and
      for this, better risk stratification and appropriate application of NIV are
      required.

PMID- 24139952
TI  - Cerebral venous thrombosis and "Dense Triangle Sign" on unenhanced head computed
      tomographic scan.
AB  - This case report describes a 21-year-old man with headache who was ultimately
      diagnosed as having cerebral venous thrombosis(CVT), a rare cause of headache in
      the emergency department that is sometimes lethal. However, correct diagnosis of
      CVT is often quite difficult because of a lack of findings in imaging studies.
      Unenhanced head computed tomography was completely normal in up to 39% of
      patients diagnosed as having CVT, but a subtle sign known as 'Dense Triangle
      Sign' was found in this case. This finding disappeared after anticoagulation
      therapy. Emergency physicians must know about this finding to diagnose this rare
      condition correctly.

PMID- 24139953
TI  - Near infrared spectrophotometry (cerebral oximetry) in predicting the return of
      spontaneous circulation in out-of-hospital cardiac arrest.
AB  - AIM: We assessed out-of-hospital cardiac arrest patients' cerebral oxygenation
      during cardiopulmonary resuscitation (CPR) using near infrared spectrophotometry
      (NIRS). We evaluated the relation between a rise in patients' cerebral saturation
      values between the start and end of CPR and return of spontaneous circulation.
      MATERIALS AND METHODS: Twenty-three patients with unwitnessed out-of-hospital
      cardiac arrest and brought to our emergency department by emergency ambulance
      were evaluated. Cerebral saturations from time of start of CPR were measured
      using NIRS. CPR was performed for a maximum of 30 min. The relation between
      cerebral saturations in patients with or without return of spontaneous
      circulation was then evaluated. RESULTS: Twenty-three patients, 12 (52.2%) female
      and 11 (47.8%) male, with a mean age of 64.09 +/- 13.66 were included. A
      correlation was determined between a rise in cerebral saturation measured
      throughout CPR and the return of spontaneous circulation (P < .001). CONCLUSION:
      Patients whose cerebral saturation values measured with NIRS rise during CPR have
      a higher post-resuscitation survival rate. Monitoring of patients during CPR with
      this non-invasive technique may be a good method for predicting return of
      spontaneous circulation.

PMID- 24139954
TI  - Influence of age in the duration of the stay and mortality of patients who remain
      in an Intensive Care Unit for a prolonged time.
AB  - BACKGROUNDS AND OBJECTIVE: The true role of the age in the prognosis of patients
      admitted in the ICU is not known. This work analyzes the influence of age on the
      duration of the stay and mortality of patients who remain in an Intensive Care
      Unit (ICU) for a long period of time. PATIENTS AND METHOD: A retrospective,
      observational study was performed with patients hospitalized >=14 days in the
      ICU. Three age groups were established: <50, 50-70 and >70 years. The influence
      of different factors on the relationship existing between stay and age was
      studied. In addition, stay and survival in the ICU, hospital and at one year were
      analyzed based on the groups. RESULTS: A total of 707 patients were included.
      Significant differences in hospital stay (P=.183) were not found among the three
      groups. The older group, which showed greater severity on admission, was the
      group undergoing the most tracheostomies (74.7%) and extrarenal purification
      (HDF) (10.8%). When the influence of factors such as APACHE II, pre-ICU stay,
      origin, tracheostomy or hemodiafiltration (HDF) were analyzed, no relation was
      found between stay and age of patient. Survival decreased as age increased.
      CONCLUSIONS: No differences were found in stay based on age, although a
      difference was found in mortality.

PMID- 24139955
TI  - The Na+ transport in gram-positive bacteria defect in the Mrp antiporter complex
      measured with 23Na nuclear magnetic resonance.
AB  - (23)Na nuclear magnetic resonance (NMR) has previously been used to monitor Na(+)
      translocation across membranes in gram-negative bacteria and in various other
      organelles and liposomes using a membrane-impermeable shift reagent to resolve
      the signals resulting from internal and external Na(+). In this work, the (23)Na
      NMR method was adapted for measurements of internal Na(+) concentration in the
      gram-positive bacterium Bacillus subtilis, with the aim of assessing the Na(+)
      translocation activity of the Mrp (multiple resistance and pH) antiporter
      complex, a member of the cation proton antiporter-3 (CPA-3) family. The sodium
      sensitive growth phenotype observed in a B. subtilis strain with the gene
      encoding MrpA deleted could indeed be correlated to the inability of this strain
      to maintain a lower internal Na(+) concentration than an external one. 

PMID- 24139956
TI  - Electronic prescribing problems reported to the Pharmacy and Provider
      ePrescribing Experience Reporting (PEER) portal.
AB  - BACKGROUND: Electronic prescribing (e-prescribing) may prevent medication errors
      caused by prescription illegibility; however, information technologies also may
      introduce different kinds of medication errors. OBJECTIVE: To identify and
      quantify e-prescribing problems reported through an electronic prescribing
      incident reporting tool in the United States. METHODS: Voluntary and anonymous
      reports to a web-based, e-prescribing incident reporting tool were collected
      during 18 months using convenience sampling. Questions in the reporting tool were
      designed to elicit information on pharmacists' experiences with e-prescribing.
      Data were analyzed to characterize the different types of e-prescribing concerns.
      RESULTS: A total of 484 reports were collected through the incident reporting
      tool. Out of 484 reports, 75% corresponded to electronic prescriptions received
      directly into pharmacies' computers and 23% were computer-generated prescriptions
      faxed to pharmacies. Most of reports corresponded to comments, complaints or
      identified unsafe conditions regarding electronic prescriptions (49%), followed
      by incidents that did not reach the patient (44%) and those that reached patients
      (6%). The majority of problems reported involved directions (24%) and quantity
      selection (12%). CONCLUSION: The use of an incident reporting tool revealed a
      variety of issues regarding e-prescribing. The majority of the issues reported in
      this study were related to directions and quantity selection. The findings in
      this study indicate that software system changes and appropriate prescriber
      training are required to decrease or eliminate some of these issues.

PMID- 24139957
TI  - White matter characterization of adolescent binge drinking with and without co
      occurring marijuana use: a 3-year investigation.
AB  - The aims of this study were to investigate the consequences of prolonged patterns
      of alcohol and marijuana use on white matter integrity and neurocognitive
      functioning in late adolescence, and examine neurodevelopmental trajectories over
      three years of regular follow-up visits. Three groups of demographically similar
      teens received assessments every 1.5 years (controls with consistently minimal
      substance use, n=16; teens who gradually increase their heavy episodic drinking
      n=17, and continuous binge drinkers with heavy marijuana use, n=21), including
      comprehensive neuropsychological evaluations, diffusion tensor imaging, and
      detailed substance use interviews. One-way ANOVA identified fifteen white matter
      clusters that significantly differed between groups at 3-year follow-up, ages 19
      22; controls consistently demonstrated higher values of tissue integrity across
      fiber tracts. Repeated measures ANOVA revealed significant declines in white
      matter integrity from baseline to 3-year follow-up in the subsample of substance
      users, along with poorer global neurocognitive performance in alcohol users with
      heavy marijuana use by the 18-month follow-up. Findings suggest healthier brain
      white matter microstructure and better neurocognitive performance for teens free
      from heavy alcohol and marijuana use. Long-term engagement in these substances
      may adversely influence white matter and increase vulnerability for development
      of neuropathology purported to underlie future risk-taking and addictive
      behaviors. 

PMID- 24139958
TI  - Object recognition deficit in early- and adult-onset schizophrenia regardless of
      age at disease onset.
AB  - Perceptual closure is the ability of the brain to recognize a complete object
      based on fragmentary information and has been known to be impaired in
      schizophrenia. Here, the neural integrity of perceptual closure in schizophrenia
      with different disease onsets was evaluated by examining the generation of event
      related potential (ERP) components (P100, N180, and N(cl)). ERPs were recorded
      from 40 patients (19 early-onset schizophrenia, "EOS" and 21 adult-onset
      schizophrenia, "AOS") and 40 age-matched healthy volunteers. Brain electric
      source analysis (BESA) was applied to localize the cerebral generators underlying
      perceptual closure. Patients showed an impaired generation of N(cl) and P100
      components. P100 and N(cl) amplitudes were significantly reduced in both AOS and
      EOS (P<0.01). Moreover, N180 and N(cl) amplitudes were significantly increased
      with age in controls and patients (P<0.01). In the case of the N(cl), there was
      also a significant interaction (P<0.001) between age and group, indicating a
      greater age-dependent N(cl) increase in controls compared to patients. Visual
      information processing during perceptual closure is impaired in schizophrenia,
      regardless of age at disease onset. The combined influence of age and group on
      the amplitude of the N(cl) might support the idea of neurodevelopmental deficits
      in schizophrenia.

PMID- 24139959
TI  - Prefrontal dysfunction in remitted depression at work reinstatement using near
      infrared spectroscopy.
AB  - A long-term and/or recurrent sickness absence from work due to depression has
      been an important health problem in industrial countries. In addition, previous
      sick leave is a risk factor of recurrence. However, many characteristics,
      especially biological aspects, have not been investigated in remitted depressive
      patients who were ready to return to work from sickness absence. Therefore, the
      purpose of this study is to clarify the pathophysiological characteristics of
      patients who were at risk for recurrence of sickness absence. We recruited 21
      patients and 16 healthy control subjects. All patients were ready to return to
      work within one month from long-term sickness absence. All subjects were examined
      for prefrontal function represented by oxyHb changes during the verbal fluency
      task (VFT) and the Stroop task using near-infrared spectroscopy. Suppressed
      prefrontal reaction during the VFT and increased prefrontal reaction during the
      Stroop task were observed in the patient group compared with the control group.
      Significantly lengthened reaction time was observed in the incongruent condition
      in the patient group during the Stroop task. Depressive patients showed impaired
      executive function measured by the Stroop task and had prefrontal dysfunction
      despite clinical remission. Residual prefrontal dysfunction may be one biological
      reason for repetitive sickness absence. 

PMID- 24139960
TI  - The brain effects of cannabis in healthy adolescents and in adolescents with
      schizophrenia: a systematic review.
AB  - Cannabis is widely used in adolescence; however, the effects of cannabis on the
      developing brain remain unclear. Cannabis might be expected to have increased
      effects upon brain development and cognition during adolescence. There is
      extensive re-organisation of grey (GM) and white matter (WM) at this time, while
      the endocannabinoid (eCB) system, which is involved in the normal physiological
      regulation of neural transmission, is still developing. In healthy adolescent
      cannabis users there is a suggestion of greater memory loss and hippocampal
      volume changes. Functional studies point to recruitment of greater brain areas
      under cognitive load. Structural and DTI studies are few, and limited by comorbid
      drug and alcohol use. The studies of cannabis use in adolescent-onset
      schizophrenia (AOS) differ, with one study pointing to extensive GM and WM
      changes. There is an intriguing suggestion that the left parietal lobe may be
      more vulnerable to the effects of cannabis in AOS. As in adult schizophrenia
      cognition does not appear to be adversely affected in AOS following cannabis use.
      Given the limited number of studies it is not possible to draw firm conclusions.
      There is a need for adequately powered, longitudinal studies. 

PMID- 24139961
TI  - The rise of mannerism in radiology.

PMID- 24139962
TI  - A quality improvement initiative to reduce unnecessary follow-up imaging for
      adnexal lesions.
AB  - Our objective was to improve the quality of pelvic ultrasound reports and
      decrease the number of physiologic and benign adnexal lesions unnecessarily
      referred for follow-up. We performed a prospective cohort study of 2 quality
      improvement interventions: academic detailing with education for the ultrasound
      radiologists and sonographers, and implementation of a national consensus
      guideline on adnexal cysts. Our primary quality outcome measure was the
      proportion of pelvic ultrasound exams in which follow-up was recommended for an
      adnexal lesion. Baseline data collection in January 2006 identified 252 pelvic
      ultrasound exams, of which 58 (23%) reported an adnexal lesion and 31 (12%)
      recommended follow-up. Retrospective review revealed that 17 of 31 (55%) reported
      adnexal lesions with follow-up recommended were physiologic or benign. After
      intervention 1, 59 of 214 (28%) pelvic ultrasound exams from January 2008
      reported an adnexal lesion, with 18 (8%) recommending follow-up. After
      intervention 2, 64 of 296 (22%) pelvic ultrasound exams from January 2011
      reported an adnexal lesion, with 16 (5%) recommending follow-up. Follow-up
      recommendations decreased 58% (12% versus 5%, P = .004), with significant
      increase in the proportion characterized as physiologic or benign (P = .001).
      Through a quality initiative aimed at appropriate description and follow-up
      recommendations for adnexal cystic lesions identified at ultrasound, we
      effectively reduced unnecessary imaging referrals. We conclude that: (1)
      acceptance of an expert consensus guideline was important to add credibility, (2)
      accessible image-rich charts are invaluable tools at point of use, and (3)
      elimination of some unnecessary imaging is under the control of the radiologist.

PMID- 24139963
TI  - Social media in radiology: early trends in Twitter microblogging at radiology's
      largest international meeting.
AB  - PURPOSE: Twitter is a social media microblogging platform that allows rapid
      exchange of information between individuals. Despite its widespread acceptance
      and use at various other medical specialty meetings, there are no published data
      evaluating its use at radiology meetings. The purpose of this study is to
      quantitatively and qualitatively evaluate the use of Twitter as a microblogging
      platform at recent RSNA annual meetings. METHODS: Twitter activity meta-data
      tagged with official meeting hashtags #RSNA11 and #RSNA12 were collected and
      analyzed. Multiple metrics were evaluated, including daily and hourly Twitter
      activity, frequency of microblogging activity over time, characteristics of the
      100 most active Twitter users at each meeting, characteristics of meeting-related
      tweets, and the geographic origin of meeting microbloggers. RESULTS: The use of
      Twitter microblogging increased by at least 30% by all identifiable meaningful
      metrics between the 2011 and 2012 RSNA annual meetings, including total tweets,
      tweets per day, activity of the most active microbloggers, and total number of
      microbloggers. Similar increases were observed in numbers of North American and
      international microbloggers. CONCLUSION: Markedly increased use of the Twitter
      microblogging platform at recent RSNA annual meetings demonstrates the potential
      to leverage this technology to engage meeting attendees, improve scientific
      sessions, and promote improved collaboration at national radiology meetings.

PMID- 24139964
TI  - Going to the gemba: identifying opportunities for improvement in radiology.

PMID- 24139965
TI  - Polycation-based nanoparticles for RNAi-mediated cancer treatment.
AB  - Cancer disorders exhibit an increasing high global incidence, in part, to an
      aging population with a high socio-economic burden. The cellular transition from
      normal to malignant state is linked to deregulated gene expression. The discovery
      of microRNA-mediated cellular regulation by the RNA interference (RNAi) pathway
      and the possibility to engage this pathway with exogenous triggers such as small
      interfering RNA (siRNA) could offer a new paradigm in anti-cancer intervention
      with RNAi-based therapeutics. The potential to silence the expression of any
      cancer-relevant protein with high selectivity promotes RNAi therapeutics as a
      more effective and safer treatment to traditional approaches. This combined with
      microRNA-based tumour profiling could pave the way for personalised approaches
      based on the genetic characteristics of the individual. Clinical translation of
      this technology, however, depends on the development of systems for effective
      delivery of the molecular medicine to the target site. Polycation-based
      nanoparticles (termed polyplexes) constitute an attractive platform for RNAi
      therapeutic delivery due to flexibility and versatility in design to overcome
      extracellular and intracellular barriers. In this review we focus on pre-clinical
      and clinical studies using polycation-based nanocarriers for RNAi mediated anti
      cancer intervention after intratumoural or intravenous administration. Potential
      RNAi targets are highlighted and special attention is given to the enhanced
      permeability and retention (EPR) effect commonly cited at the predominant
      mechanism of delivery after systemic administration. The cyclodextrin polymer
      based system now in clinical trials offers optimism that polyplexes may
      potentially be used for RNAi-mediated cancer intervention in the clinic. 

PMID- 24139966
TI  - Contribution of the immune system to bystander and non-targeted effects of
      ionizing radiation.
AB  - Considerable progress has recently been achieved in the understanding of
      molecular mechanisms involved in cellular radiation responses and radiation
      mediated microenvironmental communication. In line with that, it has become more
      and more obvious that X-irradiation causes distinct immunological effects ranging
      from anti-inflammatory activities if applied at low (<1 Gy) doses to harmful
      inflammatory side effects, radiation-induced immune modulation or induction of
      anti-tumour immune responses at higher doses. Moreover, experimental and clinical
      evidences indicate that these effects not only originate from direct nuclear
      damage but also include non-(DNA) targeted mechanisms including bystander, out of
      field distant bystander (abscopal) effects and genomic instability. The purpose
      of the present review is to elucidate immune responses that are initiated or
      affected by ionizing radiation, with a special emphasis on anti-inflammatory and
      abscopal effects and the induction of stress-induced anti-tumour immunity.

PMID- 24139967
TI  - Radiation-induced bystander effect: early process and rapid assessment.
AB  - Radiation-induced bystander effect (RIBE) is a biological process that has
      received attention over the past two decades. RIBE refers to a plethora of
      biological effects in non-irradiated cells, including induction of genetic
      damages, gene expression, cell transformation, proliferation and cell death,
      which are initiated by receiving bystander signals released from irradiated
      cells. RIBE brings potential hazards to normal tissues in radiotherapy, and
      imparts a higher risk from low-dose radiation than we previously thought.
      Detection with proteins related to DNA damage and repair, cell cycle control,
      proliferation, etc. have enabled rapid assessment of RIBE in a number of research
      systems such as cultured cells, three-dimensional tissue models and animal
      models. Accumulated experimental data have suggested that RIBE may be initiated
      rapidly within a time frame as short as several minutes after radiation. These
      have led to the requirement of techniques capable of rapidly assessing RIBE
      itself as well as assessing the early processes involved. 

PMID- 24139968
TI  - The complex interactions between radiation induced non-targeted effects and
      cancer.
AB  - Radiation induced non-targeted effects have been widely investigated in the last
      two decades for their potential impact on low dose radiation risk. In this paper
      we will give an overview of the most relevant aspects related to these effects,
      starting from the definition of the low dose scenarios. We will underline the
      role of radiation quality, both in terms of mechanisms of interaction with the
      biological matter and for the importance of charged particles as powerful tools
      for low dose effects investigation. We will focus on cell communication,
      representing a common feature of non-targeted effects, giving also an overview of
      cancer models that have explicitly considered such effects. 

PMID- 24139969
TI  - Synergistic effects of pemetrexed and amrubicin in non-small cell lung cancer
      cell lines: Potential for combination therapy.
AB  - The purpose is to examine the synergistic effect of pemetrexed (PEM) and
      amrubicin (AMR) on the proliferation of lung cancer cell lines. In vitro, dose
      dependent synergistic effects of concurrent PEM and AMRol, which is an active
      metabolite of AMR were observed in A549 and H460 cells. In real-time RT-qPCR
      analysis and western blotting, expression of the target enzymes of PEM were
      suppressed in cells treated with amrubicinol alone. In vivo, AMR/PEM treatment
      also showed synergistic antitumor activity both in A549-bearing and H520-bearing
      mice. PEM and AMR work synergistically to inhibit the proliferation of several
      different lung cancer cell lines.

PMID- 24139970
TI  - Molecular characterization showed limited genetic diversity among Salmonella
      Enteritidis isolated from humans and animals in Malaysia.
AB  - Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common
      causative agent of non-typhoidal salmonellosis in Malaysia. We aimed to
      characterize S. Enteritidis isolated from humans and animals by analyzing their
      antimicrobial resistance profiles and genotypes. A total of 111 strains were
      characterized using multiple-locus variable-number tandem repeat analysis, pulsed
      field gel electrophoresis, and antimicrobial susceptibility testing. Both typing
      methods revealed that genetically similar S. Enteritidis strains had persisted
      among human and animal populations within the period of study (2003-2008). Only
      39% of the strains were multi-drug resistant (i.e., resistant to 3 or more
      classes of antimicrobial agents), with a majority (73%) of these in low-risk
      phase (multiple antibiotic resistant index <0.20). Limited genetic diversity
      among clinical and zoonotic S. Enteritidis suggested that animals are possible
      sources of human salmonellosis. The degree of multi-drug resistance among the
      strains was generally low during the study period. 

PMID- 24139971
TI  - Streptococcus pneumoniae serotype 6C presenting as recurrent prosthetic knee
      joint infection in a patient with a history of congenital asplenia and underlying
      autoimmune disease: a case report and literature review.
AB  - This report describes a case of primary Streptococcus pneumoniae bacteremia with
      prosthetic joint infection caused by serotype 6C with recurrent infection in a
      patient with a history of congenital asplenia and underlying autoimmune disease.
      Isolates from the primary and recurrent infections were determined to be
      indistinguishable by pulsed-field gel electrophoresis. This study expands the
      conditions associated with recurrent invasive pneumococcal disease caused by
      serotype 6C. 

PMID- 24139972
TI  - Genome sequencing and population genomics in non-model organisms.
AB  - High-throughput sequencing technologies are revolutionizing the life sciences.
      The past 12 months have seen a burst of genome sequences from non-model
      organisms, in each case representing a fundamental source of data of significant
      importance to biological research. This has bearing on several aspects of
      evolutionary biology, and we are now beginning to see patterns emerging from
      these studies. These include significant heterogeneity in the rate of
      recombination that affects adaptive evolution and base composition, the role of
      population size in adaptive evolution, and the importance of expansion of gene
      families in lineage-specific adaptation. Moreover, resequencing of population
      samples (population genomics) has enabled the identification of the genetic basis
      of critical phenotypes and cast light on the landscape of genomic divergence
      during speciation. 

PMID- 24139973
TI  - Comparison of effects of long-term low-fat vs high-fat diets on blood lipid
      levels in overweight or obese patients: a systematic review and meta-analysis.
AB  - Dietary fat plays an important role in the primary prevention of cardiovascular
      disease, but long-term (>=12 months) effects of different percentages of fat in
      the diet on blood lipid levels remain to be established. Our systematic review
      and meta-analysis focused on randomized controlled trials assessing the long-term
      effects of low-fat diets compared with diets with high amounts of fat on blood
      lipid levels. Relevant randomized controlled trials were identified searching
      MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two
      studies were included in the meta-analysis. Decreases in total cholesterol
      (weighted mean difference -4.55 mg/dL [-0.12 mmol/L], 95% CI -8.03 to -1.07;
      P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference 
      3.11 mg/dL [-0.08 mmol/L], 95% CI -4.51 to -1.71; P<0.0001) were significantly
      more pronounced following low-fat diets, whereas rise in high-density lipoprotein
      (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29
      to 3.42; P<0.0001) and reduction in triglyceride levels (weighted mean difference
      -8.38 mg/dL [-0.095 mmol/L], 95% CI -13.50 to -3.25; P=0.001) were more distinct
      in the high-fat diet groups. Including only hypocaloric diets, the effects of low
      fat vs high-fat diets on total cholesterol and LDL cholesterol levels were
      abolished. Meta-regression revealed that lower total cholesterol level was
      associated with lower intakes of saturated fat and higher intakes of
      polyunsaturated fat, and increases in HDL cholesterol levels were related to
      higher amounts of total fat largely derived from monounsaturated fat (of either
      plant or animal origin) in high-fat diets (composition of which was ~17% of total
      energy content in the form of monounsaturated fatty acids, ~8% of total energy
      content in the form of polyunsaturated fatty acids), whereas increases in
      triglyceride levels were associated with higher intakes of carbohydrates. In
      addition, lower LDL cholesterol level was marginally associated with lower
      saturated fat intake. The results of our meta-analysis do not allow for an
      unequivocal recommendation of either low-fat or high-fat diets in the primary
      prevention of cardiovascular disease.

PMID- 24139974
TI  - Identification and annotation of small RNA genes using ShortStack.
AB  - Highly parallel sequencing of cDNA derived from endogenous small RNAs (small RNA
      seq) is a key method that has accelerated understanding of regulatory small RNAs
      in eukaryotes. Eukaryotic regulatory small RNAs, which include microRNAs
      (miRNAs), short interfering RNAs (siRNAs), and Piwi-associated RNAs (piRNAs),
      typically derive from the processing of longer precursor RNAs. Alignment of small
      RNA-seq data to a reference genome allows the inference of the longer precursor
      and thus the annotation of small RNA producing genes. ShortStack is a program
      that was developed to comprehensively analyze reference-aligned small RNA-seq
      data, and output detailed and useful annotations of the causal small RNA
      producing genes. Here, we provide a step-by-step tutorial of ShortStack usage
      with the goal of introducing new users to the software and pointing out some
      common pitfalls. 

PMID- 24139975
TI  - Financial versus health motivation to quit smoking: a randomized field study.
AB  - OBJECTIVE: Smoking is the most preventable cause of death, thus justifying
      efforts to effectively motivate quitting. We compared the effectiveness of
      financial versus health messages to motivate smoking cessation. Low-income
      individuals disproportionately smoke and, given their greater income constraints,
      we hypothesized that making financial costs of smoking more salient would
      encourage more smokers to try quitting. Further, we predicted that financial
      messages would be stronger in financial settings where pecuniary constraints are
      most salient. METHODS: We conducted a field study in low-income areas of New
      Haven, Connecticut using brochures with separate health vs. financial messages to
      motivate smoking cessation. Displays were rotated among community settings-check
      cashing, health clinics, and grocery stores. We randomized brochure displays with
      gain-framed cessation messages across locations. RESULTS: Our predictions were
      confirmed. Financial messages attracted significantly more attention than health
      messages, especially in financial settings. CONCLUSIONS: These findings suggest
      that greater emphasis on the financial gains to quitting and use of financial
      settings to provide cessation messages may be more effective in motivating
      quitting. Importantly, use of financial settings could open new, non-medical
      venues for encouraging cessation. Encouraging quitting could improve health,
      enhance spending power of low-income smokers, and reduce health disparities in
      both health and purchasing power.

PMID- 24139976
TI  - Cognitive behaviour therapy for health anxiety.

PMID- 24139977
TI  - Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety
      in medical patients: a multicentre randomised controlled trial.
AB  - BACKGROUND: Health anxiety has been treated by therapists expert in cognitive
      behaviour therapy with some specific benefit in some patients referred to
      psychological services. Those in hospital care have been less often investigated.
      Following a pilot trial suggesting efficacy we carried out a randomised study in
      hospital medical clinics. METHODS: We undertook a multicentre, randomised trial
      on health anxious patients attending cardiac, endocrine, gastroenterological,
      neurological, and respiratory medicine clinics in secondary care. We included
      those aged 16-75 years, who satisfied the criteria for excessive health anxiety,
      and were resident in the area covered by the hospital, were not under
      investigation for new pathology or too medically unwell to take part. We used a
      computer-generated random scheme to allocate eligible medical patients to an
      active treatment group of five-to-ten sessions of adapted cognitive behaviour
      therapy (CBT-HA group) delivered by hospital-based therapists or to standard care
      in the clinics. The primary outcome was change in health anxiety symptoms
      measured by the Health Anxiety Inventory at 1 year and the main secondary
      hypothesis was equivalence of total health and social care costs over 2 years,
      with an equivalence margin of L150. Analysis was by intention to treat. The study
      is registered with controlled-trials.com, ISRCTN14565822. FINDINGS: Of 28,991
      patients screened, 444 were randomly assigned to receive either adapted cognitive
      behaviour therapy (CBT-HA group, 219 participants) or standard care (standard
      care group, 225), with 205 participants in the CBT-HA group and 212 in the
      standard care group included in the analyses of the primary endpoints. At 1 year,
      improvement in health anxiety in the patients in the CBT-HA group was 2.98 points
      greater than in those in the standard care group (95% CI 1.64-4.33, p<0.0001),
      and twice as many patients receiving cognitive behaviour therapy achieved normal
      levels of health anxiety compared with those in the control group (13.9% vs 7.3%;
      odds ratio 2.15, 95% CI 1.09-4.23, p=0.0273). Similar differences were observed
      at 6 months and 2 years, and there were concomitant reductions in generalised
      anxiety and, to a lesser extent, depression. Of nine deaths, six were in the
      control group; all were due to pre-existing illness. Social functioning or health
      related quality of life did not differ significantly between groups. Equivalence
      in total 2-year costs was not achieved, but the difference was not significant
      (adjusted mean difference L156, 95% CI -1446 to 1758, p=0.848). INTERPRETATION:
      This form of adapted cognitive behaviour therapy for health anxiety led to
      sustained symptomatic benefit over 2 years, with no significant effect on total
      costs. It deserves wider application in medical care. FUNDING: National Institute
      for Health Research Health Technology Assessment Programme.

PMID- 24139978
TI  - Flowering and tuberization: a tale of two nightshades.
AB  - The concept of florigen, postulated in the early 1930s, has taken form after the
      identification of the FLOWERING LOCUS T (FT) protein as the flowering-inducing
      signal. Besides their role in flowering, FT genes were subsequently reported to
      play additional functions in other biological processes. This is particularly
      relevant in the nightshades, where the FT genes appear to have undergone
      considerable expansion at the functional level and gained a new role in the
      control of storage organ formation in potato (Solanum tuberosum).
      Neofunctionalization of FT homologs in the nightshades identifies these proteins
      as a new class of primary signaling components that modulate development and
      organogenesis in these agronomic relevant species. 

PMID- 24139979
TI  - Influence of the false lumen status on clinical outcomes in patients with acute
      type B aortic dissection.
AB  - OBJECTIVE: Clinical outcomes in acute type B aortic dissection patients with
      partial thrombosis of the false lumen have not been clearly elucidated. The
      purpose of this study was to investigate long-term mortality and incidence of
      surgical treatment by focusing on the status of the false lumen including partial
      thrombosis. METHODS: One hundred three patients (69 males, mean age 67 +/- 13
      years) with acute type B aortic dissection were enrolled. Patients were divided
      into three groups according to the status of the false lumen on enhanced computed
      tomography image (complete thrombosis, n = 55; partial thrombosis, n = 25;
      patent, n = 23). RESULTS: Requirement of surgical (open or endovascular)
      treatment during initial hospitalization was significantly less frequent in
      patients with complete thrombosis (0% in complete thrombosis, 16% in partial
      thrombosis, and 26% in patent). The long-term mortality (mean follow-up term,
      1143 +/- 933 days) did not differ among the three groups. Long-term surgical
      treatment-free rate was significantly lower in patients with patent false lumen.
      Cox regression analysis revealed that age (P < .01) and male sex (P = .013) were
      significant predictive factors of long-term mortality. CONCLUSIONS: In acute type
      B aortic dissection, the incidence of surgical treatment was higher in patients
      with patent false lumen during long-term follow-up, whereas status of the false
      lumen did not influence long-term mortality.

PMID- 24139981
TI  - Discussion.

PMID- 24139980
TI  - Acute reductions in mechanical wall strain precede the formation of intimal
      hyperplasia in a murine model of arterial occlusive disease.
AB  - OBJECTIVE: Intimal hyperplasia (IH) continues to plague the durability of
      vascular interventions. Employing a validated murine model, ultrasound
      biomicroscopy, and speckle-tracking algorithms, we tested the hypothesis that
      reduced cyclic arterial wall strain results in accentuated arterial wall IH.
      METHODS: A 9-0 suture was tied around the left mouse (n = 10) common carotid
      artery and a 35-gauge (outer diameter = 0.14 mm) blunt mandrel. We previously
      showed that mandrel removal results in a ~78% reduction in diameter and ~85%
      reduction in flow, with subsequent delayed induction of IH by day 28.
      Preoperative, postoperative day-4 (before measurable IH), and postoperative day
      27 circumferential wall strains were measured in locations 1, 2, and 3 mm
      proximal to the stenosis and in the same locations on the contralateral
      (nonstenosed) carotid. At postoperative day 28, arteries were perfusion fixed and
      arterial wall morphology was assessed microscopically in the same regions.
      RESULTS: Strains were the same in all locations preoperatively. Wall strain was
      decreased in all regions proximal to the stenosis by day 4 (0.26 +/- 0.01 to 0.11
      +/- 0.02; P < .001), while strains remained unchanged for the contralateral
      artery (P = .45). No statistical regional differences in mean strain or IH were
      noted at any time point for the experimental or contralateral artery. Based on
      the median, regions were divided into those with low strain (<=0.1) and high
      strain (>0.1). Average preoperative strains in both groups were the same (0.27 +/
      0.09 and 0.27 +/- 0.08). All segments in the low-strain group (n = 13)
      demonstrated significant IH formation by day 28, while only 31% of the high
      strain group demonstrated any detectable IH at day 28. (Mean low-strain intimal
      thickness = 32 +/- 20 MUm, high strain = 8.0 +/- 16 MUm; P < .01). Changes in
      cross-sectional area at diastole drove the reduction in strain in the low-strain
      group, increasing significantly from preoperatively to day 4 (P = .04), while
      lumen cross-section at systole remained unchanged (P = .46). Cross-sectional area
      at diastole and systole in the high-strain group remained unchanged from
      preoperatively to day 4 (P = .67). CONCLUSIONS: Early reduction in arterial wall
      strain is associated with subsequent development of hemodynamically induced IH.

PMID- 24139982
TI  - Familial abdominal aortic aneurysm is associated with more complications after
      endovascular aneurysm repair.
AB  - OBJECTIVE: A familial predisposition to abdominal aortic aneurysms (AAAs) is
      present in approximately one-fifth of patients. Nevertheless, the clinical
      implications of a positive family history are not known. We investigated the risk
      of aneurysm-related complications after endovascular aneurysm repair (EVAR) for
      patients with and without a positive family history of AAA. METHODS: Patients
      treated with EVAR for intact AAAs in the Erasmus University Medical Center
      between 2000 and 2012 were included in the study. Family history was obtained by
      written questionnaire. Familial AAA (fAAA) was defined as patients having at
      least one first-degree relative affected with aortic aneurysm. The remaining
      patients were considered sporadic AAA. Cardiovascular risk factors, aneurysm
      morphology (aneurysm neck, aneurysm sac, and iliac measurements), and follow-up
      were obtained prospectively. The primary end point was complications after EVAR,
      a composite of endoleaks, need for secondary interventions, aneurysm sac growth,
      acute limb ischemia, and postimplantation rupture. Secondary end points were
      specific components of the primary end point (presence of endoleak, need for
      secondary intervention, and aneurysm sac growth), aneurysm neck growth, and
      overall survival. Kaplan-Meier estimates for the primary end point were
      calculated and compared using log-rank (Mantel-Cox) test of equality. A Cox
      regression model was used to calculate the independent risk of complications
      associated with fAAA. RESULTS: A total of 255 patients were included in the study
      (88.6% men; age 72 +/- 7 years, median follow-up 3.3 years; interquartile range,
      2.2-6.1). A total of 51 patients (20.0%) were classified as fAAA. Patients with
      fAAA were younger (69 vs 72 years; P = .015) and were less likely to have ever
      smoked (58.8% vs 73.5%; P = .039). Preoperative aneurysm morphology was similar
      in both groups. Patients with fAAA had significantly more complications after
      EVAR (35.3% vs 19.1%; P = .013), with a twofold increased risk (adjusted hazard
      ratio, 2.1; 95% confidence interval, 1.2-3.7). Secondary interventions (39.2% vs
      20.1%; P = .004) and aneurysm sac growth (20.8% vs 9.5%; P = .030) were the most
      important elements accounting for the difference. Furthermore, a trend toward
      more type I endoleaks during follow-up was observed (15.6% vs 7.4%; P = .063) and
      no difference in overall survival. CONCLUSIONS: The current study shows that
      patients with a familial form of AAA develop more aneurysm-related complications
      after EVAR, despite similar AAA morphology at baseline. These findings suggest
      that patients with fAAA form a specific subpopulation and create awareness for a
      possible increase in the risk of complications after EVAR.

PMID- 24139983
TI  - The impact of bird-beak configuration on aortic remodeling of distal arch
      pathology after thoracic endovascular aortic repair with the Zenith Pro-Form TX2
      thoracic endograft.
AB  - OBJECTIVE: Structural changes and incomplete endograft apposition to the aortic
      arch (bird-beak configuration) after thoracic endovascular aortic repair are
      poorly understood. The aim of this study was to analyze the morphologic changes,
      conformability, and angulation factors in patients who underwent stainless steel
      based stent graft repair of thoracic aortic pathology. METHODS: From March 2011
      to March 2012, the study enrolled 19 patients with aortic pathology requiring
      proximal fixation in zones 2 and 3 who underwent stent graft repair using Zenith
      Pro-Form TX2 stent grafts (Cook Medical, Bloomington, Ind). For comparison,
      another 19 patients who received Zenith Z-Trak stent grafts were selected from
      December 2009 to February 2011. Chest computed tomography scans were analyzed at
      baseline, and then at 1, 6, and 12 months postoperatively. Arch angulation and
      bird-beak configuration were evaluated according to sealing zones of attachment
      by Aquarius iNtuition software (TeraRecon, San Mateo, Calif). RESULTS: The
      treated diseases included chronic type B aortic dissection in 17 patients and
      degenerative aneurysms in 21. Significant arch angle transformation was noted at
      the zone 2 level between the Pro-Form and Z-Trak treated groups (150 degrees  +/-
      11 degrees  vs 158 degrees  +/- 6 degrees ; P = .033) and left subclavian artery
      level (152 degrees  +/- 12 degrees  vs 160 degrees  +/- 8 degrees ; P = .031)
      during 1 year of follow-up. The bird-beak configuration was detected in six
      patients (32%) in the Pro-Form group and in 11 (58%) in the Z-Trak group (P =
      .096) at 1 month, and in six (32%) in the Pro-Form group and in 14 (74%) in the Z
      Trak group (P = .022) at 12 months. The mean bird-beak angle was significantly
      less in Pro-Form-treated patients at 1 month (5 degrees  +/- 9 degrees  vs 15
      degrees  +/- 13 degrees ; P = .019) and at 1 year (6 degrees  +/- 10 degrees  vs
      18 degrees  +/- 15 degrees ; P = .033). In the Pro-Form platform, a preoperative
      zone 2 angle <151.1 degrees  was a better estimation of the presence of a
      postoperative bird-beak configuration, with a sensitivity of 86% and specificity
      of 83%. CONCLUSIONS: Aortic remodeling after stainless steel stent graft repair
      of thoracic aortic pathology is a continuous process. Significant arch angle
      transformation was discovered over the zone 2 and left subclavian artery levels.
      TX2 Pro-Form stent grafts improved arch conformation after 1 year of follow-up.
      Furthermore, in the patients with dissection, a preoperative distal arch angle of
      zone 2 was predictive of postoperative bird-beak configuration, regardless of
      whether they were treated with a Pro-Form stent graft.

PMID- 24139984
TI  - The financial implications of endovascular aneurysm repair in the cost
      containment era.
AB  - OBJECTIVE: Endovascular aneurysm repair (EVAR) is associated with significant
      direct device costs. Such costs place EVAR at odds with efforts to constrain
      healthcare expenditures. This study examines the procedure-associated costs and
      operating margins associated with EVAR at a tertiary care academic medical
      center. METHODS: All infrarenal EVARs performed from April 2011 to March 2012
      were identified (n = 127). Among this cohort, 49 patients met standard commercial
      instruction for use guidelines, were treated using a single manufacturer device,
      and billed to Medicare diagnosis-related group (DRG) 238. Of these 49 patients,
      net technical operating margins (technical revenue minus technical cost) were
      calculated in conjunction with the hospital finance department. EVAR implant
      costs were determined for each procedure. DRG 238-associated costs and length of
      stay were benchmarked against other academic medical centers using University
      Health System Consortium 2012 data. RESULTS: Among the studied EVAR cohort (age
      75, 82% male, mean length of stay, 1.7 days), mean technical costs totaled
      $31,672. Graft implants accounted for 52% of the allocated technical costs.
      Institutional overhead was 17% ($5495) of total technical costs. Net mean total
      technical EVAR-associated operating margins were -$4015 per procedure. Our
      institutional costs and length of stay, when benchmarked against comparable
      centers, remained in the lowest quartile nationally using University Health
      System Consortium costs for DRG 238. Stent graft price did not correlate with
      total EVAR market share. CONCLUSIONS: EVAR is currently associated with
      significant negative operating margins among Medicare beneficiaries. Currently,
      device costs account for over 50% of EVAR-associated technical costs and did not
      impact EVAR market share, reflecting an unawareness of cost differential among
      surgeons. These data indicate that EVAR must undergo dramatic care delivery
      redesign for this practice to remain sustainable.

PMID- 24139985
TI  - Temporal patterns of the trunk muscles remain altered in a low back-injured
      population despite subjective reports of recovery.
AB  - OBJECTIVE: To compare temporal activation patterns from 24 abdominal and lumbar
      muscles between healthy subjects and those who reported recovery from recent low
      back injury (LBI). DESIGN: Cross-sectional comparative study. SETTING: University
      neuromuscular function laboratory. PARTICIPANTS: Healthy adult volunteers (N=81;
      30 LBI, 51 asymptomatic subjects). INTERVENTIONS: Trunk muscle electromyographic
      activity was collected during 2 difficulty levels of a supine trunk stability
      test aimed at challenging lumbopelvic control. MAIN OUTCOME MEASURES: Principal
      component (PC) analysis was applied to determine differences in temporal and/or
      amplitude electromyographic patterns between groups. Mixed-model analyses of
      variance were performed on PC scores that explained more than 89% of the variance
      (alpha=.05). RESULTS: Four PCs explained 89% and 96% of the variance for the
      abdominal and back muscles, respectively, with both muscle groups having similar
      shapes in the first 3 PCs. Significant interactions or group main effects were
      found for all PC scores except PC4 for the back extensors. Overall activation
      amplitudes for both the abdominal and back muscles (PC1 scores) were
      significantly (P<.05) higher for the LBI group, with both abdominal and back
      muscles of the LBI group demonstrating an increased response to the leg-loading
      phase (PC2 scores) compared with the asymptomatic group. Differences were also
      found between groups in their preparatory activity (PC3 scores), with the LBI
      group having a higher early relative amplitude of abdominal and back extensor
      activity. CONCLUSIONS: Despite perceived readiness to return to work and low pain
      scores, muscle activation patterns remained altered in this LBI group, including
      reduced synergistic coactivation and increased overall amplitudes as well as
      greater relative amplitude differences during specific phases of the movement.
      Electromyographic measures provide objective information to help guide therapy
      and may assist with determining the level of healing and return-to-work readiness
      after an LBI.

PMID- 24139986
TI  - Pulsed electromagnetic field and exercises in patients with shoulder impingement
      syndrome: a randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To evaluate the effects of pulsed electromagnetic field (PEMF) and
      exercises in reducing pain and improving function and muscle strength in patients
      with shoulder impingement syndrome (SIS). DESIGN: Double-blind, randomized
      controlled trial with a 3-month posttreatment follow-up. SETTING: Outpatient
      rehabilitation of a public hospital. PARTICIPANTS: Patients (N=56) between 40 and
      60 years of age, with a diagnosis of SIS, were randomly assigned to receive
      active PEMF (n=26; mean age, 50.1y) or placebo PEMF (n=30; mean age, 50.8y).
      INTERVENTIONS: After 3 weeks of active or placebo PEMF, both groups performed the
      same program of exercises that focused on shoulder strengthening. MAIN OUTCOME
      MEASURES: A visual analog scale, the University of California/Los Angeles
      shoulder rating scale, the Constant-Murley shoulder score, and handheld
      dynamometry for muscle strength were used as outcome measures at baseline
      (pretreatment), at 3 weeks (after active or placebo PEMF), at 9 weeks
      (postexercise), and at 3 months posttreatment. RESULTS: Patients in the active
      PEMF group had a higher level of function and less pain at all follow-up time
      frames compared with baseline (P<.05). However, the placebo PEMF group had
      increased function and reduced pain only at the 9-week and 3-month follow-ups
      (P<.05)-that is, after performing the associated exercises. For the shoulder
      dynamometry, the active PEMF group had increased strength for lateral rotation at
      9 weeks (P<.05), and increased strength for medial rotation at 9 weeks and 3
      months (both P<.05) when compared with baseline. There was no significant
      difference for shoulder strength in the placebo PEMF group (P>.05), as well as no
      significant differences (P>.05) for all outcome measures. CONCLUSIONS: The
      combination of PEMF and shoulder exercises is effective in improving function and
      muscle strength and decreasing pain in patients with SIS. However, these results
      should be carefully interpreted because of the lack of differences between
      groups.

PMID- 24139987
TI  - Microbiology in the 'omics era: from the study of single cells to communities and
      beyond.

PMID- 24139988
TI  - Structural characterization of a noncovalent complex between ubiquitin and the
      transactivation domain of the erythroid-specific factor EKLF.
AB  - Like other acidic transactivation domains (TAD), the minimal TAD from the
      erythroid-specific transcription factor EKLF (EKLFTAD) has been shown to
      contribute both to its transcriptional activity as well as to its ubiquitin(UBI)
      mediated degradation. In this article, we examine the activation-degradation role
      of the acidic TAD of EKLF and demonstrate that the first 40 residues (EKLFTAD1)
      within this region form a noncovalent interaction with UBI. Nuclear magnetic
      resonance (NMR) structural studies of an EKLFTAD1-UBI complex show that EKLFTAD1
      adopts a 14-residue alpha helix that forms the recognition interface with UBI in
      a similar manner as the UBI-interacting helix of Rabex5. We also identify a
      similar interaction between UBI and the activation-degradation region of SREBP1a,
      but not with the activation-degradation regions of p53, GAL4, and VP16. These
      results suggest that select activation-degradation regions like the ones found in
      EKLF and SREBP1a function in part through their ability to form noncovalent
      interactions with UBI. 

PMID- 24139989
TI  - Conformational dynamics inside amino-terminal disease hotspot of ryanodine
      receptor.
AB  - The N-terminal region of both skeletal and cardiac ryanodine receptor is a
      disease mutation hotspot. Recently, a crystal structure of the RyR1 fragment
      (residues 1-559) was solved. This N-terminal structure contains three separate
      domains, A, B, and C, and was docked into a central vestibule in a full-length
      RyR1 cryo-EM map. Here, we reconstructed three-dimensional cryo-EM structures of
      two GFP-tagged RyR2s with GFP inserted after residue Glu-310 and Ser-437,
      respectively. The structures of RyR2E310-GFP and RyR2S437-GFP displayed an extra
      mass on domain B and C, directly validating the predicted docking model. Next, we
      revealed domain movements in molecular dynamics flexible fitting models in both
      the closed and open state cryo-EM maps. To further probe the conformational
      changes, we generated FRET pairs by inserting CFP or YFP in two selected domains,
      FRET studies of three dual-insertion pairs and three co-expressed single
      insertion pairs showed the dynamic structural changes within the N-terminal
      domains. 

PMID- 24139990
TI  - Alternative folding nuclei definitions facilitate the evolution of a symmetric
      protein fold from a smaller peptide motif.
AB  - Protein 3 degrees  structure symmetry is a defining feature of nearly one-third
      of protein folds and is generally thought to result from a combination of gene
      duplication, fusion, and truncation events. Such events represent major
      replication errors, involving substantial alteration of protein 3 degrees 
      structure and causing regions of exact repeating 1 degrees  structure, both of
      which are generally considered deleterious to protein folding. Thus, the
      prevalence of symmetric protein folds is counterintuitive and suggests a
      specific, yet unexplained, robustness. Using a designed beta-trefoil protein, we
      show that purely symmetric 1 degrees  structure enables utilization of
      alternative definitions of the critical folding nucleus in response to gross
      structural rearrangement. Thus, major replication errors producing 1 degrees 
      structure symmetry can conserve foldability. The results provide an explanation
      for the prevalence of symmetric protein folds and highlight a critical role for 1
      degrees  structure symmetry in protein evolution. 

PMID- 24139991
TI  - Asp44 stabilizes the Trp41 gate of the M2 proton channel of influenza A virus.
AB  - Channel gating and proton conductance of the influenza A virus M2 channel result
      from complex pH-dependent interactions involving the pore-lining residues His37,
      Trp41, and Asp44. Protons diffusing from the outside of the virus protonate
      His37, which opens the Trp41 gate and allows one or more protons to move into the
      virus interior. The Trp41 gate gives rise to a strong asymmetry in the
      conductance, favoring rapid proton flux only when the outside is at acid pH.
      Here, we show that the proton currents recorded for mutants of Asp44, including
      D44N found in the A/FPV/Rostock/34 strain, lose this asymmetry. Moreover, NMR and
      MD simulations show that the mutations induce a conformational change similar to
      that induced by protonation of His37 at low pH, and decrease the structural
      stability of the hydrophobic seal associated with the Trp41 gate. Thus, Asp44 is
      able to determine two important properties of the M2 proton channel. 

PMID- 24139992
TI  - Use of ACISTTM contrast injection device in carotid artery stenting in high
      surgical-risk patients.
AB  - OBJECTIVE: The objective is to see if use of the ACISTTM device during carotid
      stenting would be feasible without an increase in primary end points when
      compared to historic controls. BACKGROUND: Carotid stenting has been studied as
      an effective alternative to endarterectomy in high-surgical-risk patients.
      Traditional angiography involves manual contrast injection. It leads to excess
      contrast volume and greater fluoroscopy times. The Acist contrast injection
      device helps with the regulation and lowering of contrast volume. METHODS: This
      is a consecutive, non-randomized, open-label, multiple-operator-based study.
      Inclusion criteria were as follows: (a) subject is considered at high risk for
      carotid endarterectomy, (b) subject requires percutaneous carotid angioplasty and
      stenting for carotid disease, and (c) subject must be asymptomatic with >=80%
      stenosis of the internal and/or common carotid artery. The primary end points
      measured were, death from any cause, myocardial infarction, transient ischemic
      attack or stroke within 30 days of intervention. Secondary end points were
      contrast volume and fluoroscopy time. RESULTS: Four operators in one institution
      performed interventions from June 2007 to May 2012 on 133 consecutive patients.
      They were predominantly men (59.4%). The mean age (SD) was 73.64 (7.952) years.
      Stroke occurred in 3% (N=4), transient ischemic attack in 0.8% (N=1) and
      myocardial infarction in 0.8% (N=1). Three study subjects died (2.3%). The mean
      (SD) contrast volume was 121.24 (67.79) mL. The mean (SD) fluoroscopy time was
      18.34 (11.31) minutes. CONCLUSIONS: The use of the ACISTTM device was feasible in
      carotid stenting in a high-risk population without an increase in end points when
      compared to historic controls.

PMID- 24139993
TI  - DNA strand breaks (comet assay) in blood lymphocytes from wild bottlenose
      dolphins.
AB  - The comet assay was carried out on blood lymphocytes from a large number of wild
      dolphins (71 from Indian River Lagoon, FL, USA; 51 from Charleston Harbor, SC,
      USA) and provides a baseline study of DNA strand breaks in wild dolphin
      populations. There were no significant differences in the comet assay (% DNA in
      tail) results between the different age and sex categories. Significant
      difference in DNA strand breaks were found between Charleston Harbor dolphins
      (median--17.4% DNA in tail) and Indian River Lagoon dolphins (median--14.0% DNA
      in tail). A strong correlation found between T-cell proliferation and DNA strand
      breaks in dolphin lymphocytes suggests that dolphins with a high numbers of DNA
      strand breaks have a decreased ability to respond to infection. Higher
      concentrations of genotoxic agents in Charleston Harbor compared with Indian
      River lagoon may have been one of the causes of higher DNA strand breaks in these
      dolphins.

PMID- 24139994
TI  - Intraoral Spitz nevus: case report and literature review.
AB  - Spitz nevi account for approximately 1% of all melanocytic nevi of the skin in
      children. Although Spitz nevi often develop in the skin of the head and neck,
      intraoral Spitz nevi are rare. These nevi contain epithelioid and spindle cells
      and exhibit cytologic and architectural atypia when compared with routine
      melanocytic nevi, and may be mistaken for atypical Spitz tumor, Spitzoid
      melanoma, or conventional melanoma. Here, we report a Spitz nevus on the buccal
      mucosa of an 11-year-old boy. The tumor was composed of a proliferation of mostly
      epithelioid melanocytes with a smaller spindle cell component. The melanocytes
      were positive for S100, MART-1, and p16 proteins, with HMB-45-positive cells
      located only in the basal cell layer and superficial lamina propria. Less than 5%
      of the nuclei were positive for MIB-1, and there were no mitotic figures. We
      review the literature on 7 previously reported cases of Spitz nevi. 

PMID- 24139995
TI  - Patient safety analysis of the ED care of patients with heart failure and COPD
      exacerbations: a multicenter prospective cohort study.
AB  - OBJECTIVES: For emergency department (ED) patients with acute exacerbations of
      heart failure and chronic obstructive pulmonary disease (COPD), we aimed to
      assess the adherence to evidence-based care and determine the proportion that
      experienced adverse events. METHODS: An expert panel identified critical actions
      for ED care of heart failure and COPD patients based on clinical practice
      guidelines. We collected outcome data for discharged ED patients >age 50 with
      acute heart failure or COPD in a multicenter prospective cohort study at five
      academic EDs. We measured 3 flagged outcomes: return ED visit, admission, or
      death within 14 days. Three trained physician reviewers reviewed case summaries
      for adverse event determination (flagged outcomes related to healthcare
      received). We evaluated health records for adherence to the critical actions for
      each condition. RESULTS: We identified 122 (7.0%) flagged outcomes among 1,718
      enrolled patients (61 heart failure, 59 COPD and 2 dual diagnoses). The mean age
      was 74.2 (SD 10.4) and 44.3% were female. Among 10 critical actions for heart
      failure and 13 for COPD, a mean proportion of 9.4/10 and 11.0/13 were adhered to
      respectively. We identified 12 adverse events (9.8%, 95%CI: 5.6-16.5%), all of
      which were deemed preventable, including 1 death. The most common contributors
      were unsafe disposition decisions (10/12, 83.3%) and diagnostic issues (5/12,
      41.7%). Patients who died with heart failure were statistically significantly
      less likely to have guideline adherent care (P = .02). CONCLUSIONS: A small
      proportion of return ED visits were related to index care. We believe there is
      need for improvement around disposition decision making for both conditions to
      reduce the highly preventable and clinically significant adverse events we found.

PMID- 24139996
TI  - Timing and appropriateness of initial antibiotic therapy in newly presenting
      septic patients.
AB  - OBJECTIVE: To determine the effectiveness of antibiotic regimens and time to
      antibiotics in septic patients admitted to an intensive care unit from the
      emergency department. METHODS: A retrospective case-control study of patients
      with sepsis syndromes admitted from the emergency department between August 2010
      and July 2011 was conducted. Standard demographic information, time frames for
      written antibiotic orders and administration, and information regarding site of
      culture, organisms identified, sensitivities, and antibiotic effectiveness were
      documented. RESULTS: Four hundred medical records were reviewed; 184 patients met
      the study inclusion criteria and were included in the final analysis. Simplified
      Acute Physiology Scores II and Sequential Organ Failure Assessment scores were 49
      and 6, respectively, and overall in-hospital mortality was 20.7%. Patients with
      positive blood cultures had higher Simplified Acute Physiology Scores II scores
      (56.0 vs 46.0, P = .0125). Serum lactate levels were also significantly higher in
      the in-hospital mortality group (3.2 vs 2.1, P = .0068). Computerized physician
      order entry dramatically decreased the median times to the last appropriate
      antibiotic administration (3.183 hours vs 6.992 hours, P < .0001) but did not
      alter mortality (20.6% vs 20.8%). Appropriateness of empiric antibiotic regimens
      was similar between patients surviving and those who died during their hospital
      stay (63.5% vs 68.8%, P = .58). CONCLUSIONS: Median times to the first antibiotic
      administration and last needed appropriate antibiotic administration were less
      than 3 and 5 hours, respectively; these times were similar between patients who
      survived and those who died during their hospital stay. Patients with a serum
      lactate level higher than 2.5 mmol/L were associated with a 2.5-times increased
      risk of mortality.

PMID- 24139997
TI  - Overuse of energy drinks: why death?

PMID- 24139998
TI  - Radiofrequency ablation for early-stage breast cancer: treatment outcomes and
      practical considerations.
AB  - BACKGROUND: Radiofrequency ablation (RFA) for early-stage breast cancer has the
      potential advantage of being a less invasive treatment associated with improved
      cosmetic outcome. The aim of this review was to summarise the reported treatment
      outcomes of ultrasound-guided RFA for early-stage breast cancer and to highlight
      practical considerations with regard to this treatment. METHODS: A search of the
      English-language literature concerning RFA for breast cancer treatment was
      performed. RESULTS: RFA is a technique that can be safely applied in patients
      with early-stage breast cancer, which is restricted to cT1-T2N0 ductal carcinoma
      with radiologically defined borders without any signs of multifocality or
      multicentricity. However, before RFA can be adopted as local therapy for early
      stage breast cancer, more research is needed to assess the post-treatment
      pathological complete response and margin status, the long-term oncologic outcome
      in comparison to current standard breast conserving therapy and the potential
      cosmetic superiority of percutaneous RFA. CONCLUSION: RFA appeared to be a
      feasible technique for the treatment of early-stage breast cancer, but
      considerable practical considerations form an obstacle to introduce RFA as a
      standard of care.

PMID- 24139999
TI  - Spontaneous regression of metastatic melanoma - clinical evidence of the abscopal
      effect.
AB  - INTRODUCTION: Metastatic melanoma is poorly understood. Regression of primary
      lesions has been associated with poor prognosis, but spontaneous regression of
      all metastatic disease is clearly beneficial. A patient's own immune responses
      occasionally appear to stimulate spontaneous regression of metastatic disease in
      melanoma. PATIENTS AND METHODS: We present six interesting cases of complete or
      nearly complete spontaneous regression of metastatic melanoma, suggest possible
      causes and review the literature. RESULTS AND CONCLUSIONS: These cases show clear
      radiological, pathological or clinical evidence of spontaneous regression of
      metastatic melanoma. This remains a poorly understood phenomena warranting
      further investigation and may prove useful in the development of immune mediated
      solutions.

PMID- 24140000
TI  - Association of T-cell co-regulatory protein expression with clinical outcomes
      following radical cystectomy for urothelial carcinoma of the bladder.
AB  - PURPOSE: Expression of T-cell co-regulatory proteins has been associated with
      worse outcomes in patients with UCB. We aimed to confirm these findings.
      MATERIALS AND METHODS: The study comprised tissue microarrays from 302
      consecutive UCB patients treated with RC and lymphadenectomy between 1988 and
      2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium
      controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by
      immunohistochemistry. RESULTS: B7-H3 and PD-1 expression were increased in
      cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%,
      respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of
      cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated
      between the primary tumors and metastatic nodes, with concordance rates of 90%,
      86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated
      with clinicopathologic features, disease recurrence, cancer-specific or overall
      mortality. However, for the subgroup of patients with organ-confined disease (n =
      96), B7-H1 expression was associated with an increased risk of overall mortality
      (p = 0.02) on univariate and trended toward an association on multivariate
      analyses (p = 0.06). CONCLUSIONS: B7-H1, B7-H3 and PD-1 are altered in a large
      proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in
      cancer versus normal urothelium. High correlation between expression in LN and
      expression in RC specimens was observed. While expression was not associated with
      clinicopathologic features or standard outcomes in all patients, B7-H1 expression
      predicted overall mortality after RC in the subset of patients with organ
      confined UCB.

PMID- 24140001
TI  - Culture temperature affects gene expression and metabolic pathways in the 2
      methylisoborneol-producing cyanobacterium Pseudanabaena galeata.
AB  - A volatile metabolite, 2-methylisoborneol (2-MIB), causes an unpleasant taste and
      odor in tap water. Some filamentous cyanobacteria produce 2-MIB via a two-step
      biosynthetic pathway: methylation of geranyl diphosphate (GPP) by methyl
      transferase (GPPMT), followed by the cyclization of methyl-GPP by monoterpene
      cyclase (MIBS). We isolated the genes encoding GPPMT and MIBS from Pseudanabaena
      galeata, a filamentous cyanobacterium known to be a major causal organism of 2
      MIB production in Japanese lakes. The predicted amino acid sequence showed high
      similarity with that of Pseudanabaena limnetica (96% identity in GPPMT and 97%
      identity in MIBS). P. galeata was cultured at different temperatures to examine
      the effect of growth conditions on the production of 2-MIB and major metabolites.
      Gas chromatograph-mass spectrometry (GC-MS) measurements showed higher
      accumulation of 2-MIB at 30  degrees C than at 4  degrees C or 20  degrees C
      after 24 h of culture. Real-time-RT PCR analysis showed that the expression
      levels of the genes encoding GPPMT and MIBS decreased at 4  degrees C and
      increased at 30  degrees C, compared with at 20  degrees C. Furthermore,
      metabolite analysis showed dramatic changes in primary metabolite concentrations
      in cyanobacteria grown at different temperatures. The data indicate that changes
      in carbon flow in the TCA cycle affect 2-MIB biosynthesis at higher temperatures.

PMID- 24140002
TI  - Potassium in agriculture--status and perspectives.
AB  - In this review we summarize factors determining the plant availability of soil
      potassium (K), the role of K in crop yield formation and product quality, and the
      dependence of crop stress resistance on K nutrition. Average soil reserves of K
      are generally large, but most of it is not plant-available. Therefore, crops need
      to be supplied with soluble K fertilizers, the demand of which is expected to
      increase significantly, particularly in developing regions of the world. Recent
      investigations have shown that organic exudates of some bacteria and plant roots
      play a key role in releasing otherwise unavailable K from K-bearing minerals.
      Thus, breeding for genotypes that have improved mechanisms to gain access to this
      fixed K will contribute toward more sustainable agriculture, particularly in
      cropping systems that do not have access to fertilizer K. In K-deficient crops,
      the supply of sink organs with photosynthates is impaired, and sugars accumulate
      in source leaves. This not only affects yield formation, but also quality
      parameters, for example in wheat, potato and grape. As K has beneficial effects
      on human health, its concentration in the harvest product is a quality parameter
      in itself. Owing to its fundamental roles in turgor generation, primary
      metabolism, and long-distance transport, K plays a prominent role in crop
      resistance to drought, salinity, high light, or cold as well as resistance to
      pests and pathogens. Despite the abundance of vital roles of K in crop
      production, an improvement of K uptake and use efficiency has not been a major
      focus of conventional or transgenic breeding in the past. In addition, current
      soil analysis methods for K are insufficient for some common soils, posing the
      risk of imbalanced fertilization. A stronger prioritization of these areas of
      research is needed to counter declines in soil fertility and to improve food
      security. 

PMID- 24140003
TI  - Oral gabapentin treatment accentuates nerve and peripheral inflammatory responses
      following experimental nerve constriction in Wistar rats.
AB  - Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control
      neuropathic pain. This study aimed at evaluating whether oral GBP treatment could
      improve nerve inflammation response after sciatic nerve constriction in
      association with selected pain and motor spontaneous behavior assessments in
      Wistar rats. We evaluated nerve myeloperoxidase (MPO) and inflammatory cytokines
      on the 5th day post-injury, time in which nerve inflammation is ongoing. In
      addition, the role of GBP on carrageenan-induced paw edema and peritoneal cell
      migration was analyzed. GBP was given by gavage at doses of 30, 60 and 120mg/kg,
      60min prior to chronic constriction of the sciatic nerve (CCSN) and during 5 days
      post-injury, 12/12h. CCSN animals treated with saline were used as controls and
      for behavioral and inflammation assessments untreated sham-operated rats were
      also used. On the 5th day, GBP (60 and 120mg/kg) alleviated heat-induced
      hyperalgesia and significantly increased delta walking scores in CCSN animals,
      the latter suggesting excitatory effects rather than sedation. GBP (60mg/kg)
      significantly increased nerve MPO, TNF-alpha, and IL-1beta levels, comparing with
      the saline group. GBP (120mg/kg) reduced the anti-inflammatory cytokine IL-10
      nerve levels compared with the CCSN saline group. Furthermore, GBP (60 and
      120mg/kg) increased carrageenan-induced paw edema and peritoneal macrophage
      migration compared with the CCSN saline group. Altogether our findings suggest
      that GBP accentuates nerve and peripheral inflammatory response, however
      confirmed its analgesic effect likely due to an independent CNS-mediated
      mechanism, and raise some concerns about potential GBP inflammatory side effects
      in widespread clinical use. 

PMID- 24140004
TI  - Right hemisphere advantage in processing Cantonese level and contour tones:
      evidence from dichotic listening.
AB  - The brain lateralization pattern of Cantonese tonal processing was examined with
      the dichotic listening (DL) paradigm. Three factors were manipulated
      systematically in the study. First, the processing of level tones was compared
      with that of contour tones. Second, the influence of a linguistic context in
      tonal processing was studied by contrasting the patterns of brain lateralization
      for real syllables, pseudo-syllables, and hums. Finally, the discrimination and
      the identification tasks were used to test how processing depth might modulate
      the results obtained. A right hemisphere advantage (RHA) was obtained regardless
      of tone type, stimulus type, and task. In addition, the performance on level
      tones was in general better than that on contour tones. These findings suggest
      that Cantonese speakers are highly sensitive to the acoustic features of lexical
      tones, which supports the acoustic view about tonal processing. 

PMID- 24140005
TI  - Histone deacetylase activity is altered in brain areas from aged rats.
AB  - It has been described that histone acetylation levels are decreased in several
      cellular and in vivo neurodegeneration models as well as in normal brain aging,
      although the impact of the aging process on histone deacetylases (HDAC) activity
      yet remains poorly understood. Therefore, our aim was to evaluate the effect of
      the aging process on HDAC activity in hippocampi and frontal cortices from 3 and
      18-months-old Wistar rats. The animals were decapitated at different times of
      day, in the early morning and in afternoon. HDAC activity was increased in
      hippocampus from the aged group. Besides, the hippocampal HDAC activity was also
      significantly increased in early morning. A significant interaction between age
      and time of the day was observed in frontal cortices, given that the HDAC
      activity was higher in early morning in the aged group. These data support the
      hypothesis that the aging-related dysfunction may be related, at least in part,
      to acetylation imbalance through HDAC activity in rat brain. 

PMID- 24140006
TI  - A diet high in alpha-linolenic acid and monounsaturated fatty acids attenuates
      hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet
      induced obese rats.
AB  - This study investigated the efficacy of the plant-based n-3 fatty acid, alpha
      linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high
      fat (55% energy) diets containing high oleic canola oil, canola oil, a
      canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12
      weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass,
      liver weight, glucose and lipid metabolism, inflammation and molecular markers of
      fatty acid oxidation, synthesis, desaturation and elongation did not account for
      this effect. The C/F group had the highest total n-3 and EPA in hepatic
      phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid
      (n-6) concentrations. In conclusion, the C/F diet with the highest content of the
      plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty
      acid profile. 

PMID- 24140007
TI  - FhuA interactions in a detergent-free nanodisc environment.
AB  - TonB-dependent membrane receptors from bacteria have been analyzed in detergent
      containing solution, an environment that may influence the role of ligand in
      inducing downstream interactions. We report reconstitution of FhuA into a
      membrane mimetic: nanodiscs. In contrast to previous results in detergent, we
      show that binding of TonB to FhuA in nanodiscs depends strongly on ferricrocin.
      The stoichiometry of interaction is 1:1 and the binding constant KD is ~200nM; an
      equilibrium affinity that is ten-fold lower than reported in detergent. FhuA in
      nanodiscs also forms a high-affinity binding site for colicin M (KD ~3.5nM),
      while ferricrocin renders FhuA refractory to colicin binding. Together, these
      results demonstrate the importance of the ligand in regulating receptor
      interactions and the advantages of nanodiscs to study beta-barrel membrane
      proteins in a membrane-like environment. 

PMID- 24140008
TI  - Treatment of influenza virus with beta-propiolactone alters viral membrane
      fusion.
AB  - Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce
      viral vaccines. Although BPL has been described to chemically modify nucleic
      acids, its effect on viral proteins, potentially affecting viral infectivity,
      remains poorly studied. Here, a H3N2 strain of influenza virus was submitted to
      treatment with various BPL concentrations (2-1000MUM). Cell infectivity was
      progressively reduced and entirely abolished at 1mM BPL. Virus fusion with
      endosome being a critical step in virus infection, we analyzed its ability to
      fuse with lipid membrane after BPL treatment. By monitoring calcein leakage from
      liposomes fusing with the virus, we measured a decrease of membrane fusion in a
      BPL dose-dependent manner that correlates with the loss of infectivity. These
      data were complemented with cryo transmission electron microscopy (cryoTEM) and
      cryo electron tomography (cryoET) studies of native and modified viruses. In
      addition, a decrease of leakage irrespective of BPL concentration was measured
      suggesting that the insertion of HA2 fusion peptide into the target membrane was
      inhibited even at low BPL concentrations. Interestingly, mass spectrometry
      revealed that HA2 and M1 matrix proteins had been modified. Furthermore, fusion
      activity was partially restored by the protonophore monensin as confirmed by
      cryoTEM and cryoET. Moreover, exposure to amantadine, an inhibitor of M2 channel,
      did not alter membrane fusion activity of 1mM BPL treated virus. Taken together
      these results show that BPL treatment inhibits membrane fusion, likely by
      altering function of proteins involved in the fusion process, shedding new light
      on the effect of BPL on influenza virus. 

PMID- 24140009
TI  - Mapping of sites facing aqueous environment of voltage-gated proton channel at
      resting state: a study with PEGylation protection.
AB  - Hv1 (also named, voltage-sensor only protein, VSOP) lacks an authentic pore
      domain, and its voltage sensor domain plays both roles in voltage sensing and
      proton permeation. The activities of a proton channel are intrinsic to protomers
      of Hv1, while Hv1 is dimeric in biological membranes; cooperative gating is
      exerted by interaction between two protomers. As the signature pattern conserved
      among voltage-gated channels and voltage-sensing phosphatase, Hv1 has multiple
      arginines intervened by two hydrophobic residues on the fourth transmembrane
      segment, S4. S4 moves upward relative to other helices upon depolarization,
      causing conformational change possibly leading to the formation of a proton
      selective conduction pathway. However, detailed mechanisms of proton-selectivity
      and gating of Hv1 are unknown. Here we took an approach of PEGylation protection
      assay to define residues facing the aqueous environment of mouse Hv1 (mHv1).
      Accessibilities of two maleimide molecules, N-ethylmaleimide (NEM) and 4
      acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AMS), were examined on
      cysteine introduced into individual sites. Only the first arginine on S4 (R1:
      R201) was inaccessible by NEM and AMS in mHv1. This is consistent with previous
      results of electrophysiology on the resting state channel, suggesting that the
      accessibility profile represents the resting state of mHv1. D108, critical for
      proton selectivity, was accessible by AMS and NEM, suggesting that D108 faces the
      vestibule. F146, a site critical for blocking by a guanidinium-reagent, was
      accessible by NEM, suggesting that F146 also faces the inner vestibule. These
      findings suggest an inner vestibule lined by several residues on S2 including
      F146, D108 on S1, and the C-terminal half of S4. 

PMID- 24140010
TI  - Evaluation of clinical parameters during and after treatment of attack in
      patients with clinically isolated syndrome: comparison of the results with that
      of multiple sclerosis patients.
AB  - OBJECTIVES: The aim of the present study was to examine the changes in the
      measurement of functions during and after pulse methylprednisolone (MP) treatment
      during a clinically isolated syndrome (CIS) attack, using the multiple sclerosis
      functional composite (MSFC) and Expanded Disability Status Scale (EDSS), and to
      compare the results with that of MS patients. PATIENTS AND METHOD: The present
      study included 44 patients with CIS and 26 patients with clinically definite
      multiple sclerosis (MS), as the control group. All patients were having an acute
      attack and were treated with 1000-mg intravenous methylprednisolone. The scales
      were administered before-and after-treatment, and at 30 days after treatment.
      RESULTS: A 5-days treatment was adequate in 36.9% of CIS patients and 62.5% of MS
      patients (p=0.003). A moderate correlation was found between Auditory Consonant
      Trigram Test (ACT) and paced auditory serial addition test in CIS patients before
      treatment. A poor correlation was found between EDSS scores and ACT in CIS
      patients at all measurement periods. The level of correlation between EDSS and
      ACT scores was similar in MS patients. CONCLUSION: Although MS and CIS patients
      show similar response to corticosteroid treatment and had similar fatigue
      characteristics, overall cognitive functioning was better in CIS patients.

PMID- 24140011
TI  - Life-span plasticity of the brain and cognition: from questions to evidence and
      back.
AB  - Experience-related changes induced by modification of environment, physical
      exercise, or cognitive training affect brain structure and function. Research on
      brain plasticity and its relationship to experiential changes gathers momentum
      and attracts significant public interest. This collection of papers is based on
      presentation at the First International Conference on Life-Span Plasticity of
      Brain and Behavior: A Cognitive Neuroscience Perspective that took place in
      Detroit, MI, on October 12-14, 2011. The conference honored Margret M. and Paul
      B. Baltes, the pioneers of life-span developmental psychology who initiated some
      of the first studies on experience- and training-related changes in cognition
      across the life span. 

PMID- 24140012
TI  - Polyploidization in liver tissue.
AB  - Polyploidy (alias whole genome amplification) refers to organisms containing more
      than two basic sets of chromosomes. Polyploidy was first observed in plants more
      than a century ago, and it is known that such processes occur in many eukaryotes
      under a variety of circumstances. In mammals, the development of polyploid cells
      can contribute to tissue differentiation and, therefore, possibly a gain of
      function; alternately, it can be associated with development of disease, such as
      cancer. Polyploidy can occur because of cell fusion or abnormal cell division
      (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a
      common characteristic of the mammalian liver. Polyploidization occurs mainly
      during liver development, but also in adults with increasing age or because of
      cellular stress (eg, surgical resection, toxic exposure, or viral infections).
      This review will explore the mechanisms that lead to the development of polyploid
      cells, our current state of understanding of how polyploidization is regulated
      during liver growth, and its consequence on liver function. 

PMID- 24140013
TI  - Characterization of the environmental quality of sediments from two estuarine
      systems based on different in-vitro bioassays.
AB  - This study characterizes the environmental quality of sediments from the Arade
      and Guadiana estuaries using different in-vitro bioassays: a) fish hepatoma cell
      line (PLHC-1) to determine cytotoxicity and presence of CYP1A and oxidative
      stress inducing agents; b) gonad subcellular fractions from sea bass
      (Dicentrarchus labrax) to detect compounds that are likely to act as endocrine
      disrupters by interfering with the synthesis of androgens (CYP17, CYP11beta) and
      estrogens (CYP19). Approximately 60% of extracts from the Arade estuary were
      cytotoxic when tested at 60 mg eQsed/mL, while only one sample from Guadiana
      showed cytotoxicity. Sediments from Arade collected close to harbours and waste
      water effluents were enriched with CYP1A inducing agents, while those from the
      upper Guadiana induced oxidative stress in PLHC-1 cells. On the other hand,
      several extracts from both estuaries were able to significantly inhibit CYP17,
      CYP11beta and CYP19 activities in gonad subcellular fractions of sea bass, which
      indicates the presence of endocrine disrupters, particularly in several sites
      from the Arade estuary. Overall, the study highlights the usefulness of in-vitro
      bioassays to identify those sediments that could pose risk to aquatic organisms
      and that require further action to improve their environmental quality. 

PMID- 24140014
TI  - Variability of the hemocyte parameters of cultivated mussel Mytilus
      galloprovincialis (Lmk 1819) in Sabaudia (Latina, Italy) coastal lagoon.
AB  - The Sabaudia's lake consists of a protected coastal lagoon, located in the
      central Italy, historically characterized by recurrent mortality events of marine
      fauna during warmer months. A field study was monthly conducted on mussels
      Mytilus galloprovincialis cultivated inside the lagoon, measuring hemocyte
      parameters as total circulating count (THC), viability (HV), spreading and
      oxidative response to in vitro phagocytosis stimulation. A depression of the
      immune response was observed during the spring season, as indicated by higher
      values of hemocyte circularity and lower luminescence levels related to
      respiratory burst, also associated to modulation of THC and HV. The water
      temperature and the oxygen concentration appeared as the major environmental
      factors having influence on the phagocytosis activity. Therefore, the hemocyte
      variations have been intended as early danger signal to evaluate the
      immunodepression induced by the environmental stressors which could reveal in
      advance the development of critical situations for mussel survival.

PMID- 24140015
TI  - Longitudinal analysis of leukocyte differentials in peripheral blood of patients
      with acute respiratory viral infections.
AB  - BACKGROUND: Leukocyte counts and differentials are commonly acquired in patients
      with suspected respiratory viral infections and may contribute diagnostic
      information. However, most published work is limited to a single timepoint at
      initial presentation to a medical provider, which may correspond to widely
      varying points in the course of disease. OBJECTIVES: To examine the temporal
      development and time-dependent utility of routine leukocyte differentials in the
      diagnosis of respiratory viral infections. STUDY DESIGN: We analyzed data from
      recent experimental human challenges with influenza A/H3N2, human rhinovirus
      (HRV), and respiratory syncytial virus (RSV). Routine clinical lab cell counts
      and differentials were measured daily from the time period immediately prior to
      inoculation through the eventual resolution of symptomatic disease. RESULTS:
      Approximately 50% of challenged individuals developed symptoms and viral shedding
      consistent with clinical disease. Subpopulations of WBC showed marked differences
      between symptomatic and asymptomatic individuals over time, but these changes
      were much more profound and consistent in influenza infection. Influenza-infected
      subjects develop both relative lymphopenia and relative monocytosis, both of
      which closely mirror symptom development in time. A lymphocyte:monocyte ratio of
      <2 correctly classifies 100% of influenza (but not RSV or HRV) infected subjects
      at the time of maximal symptoms. CONCLUSIONS: Leukocyte differentials may suggest
      a viral etiology in patients with upper respiratory infection, but are not
      sufficient to allow differentiation between common viruses. Timing of data
      acquisition relative to the disease course is a key component in determining the
      utility of these tests.

PMID- 24140016
TI  - Assessing statistical views of natural selection: Room for non-local causation?
AB  - Recently some philosophers (the "statisticalists") have emphasized a potentially
      irreconcilable conceptual antagonism between the statistical characterization of
      natural selection (derived from population genetics) and the standard scientific
      discussion of natural selection in terms of forces and causes. Other philosophers
      have developed an account of the causal character of selectionist statements
      represented in terms of counterfactuals. I examine the compatibility between such
      statisticalism and counterfactually based causal accounts of natural selection
      (and related arguments about counterfactuals and causality) by distinguishing two
      distinct statisticalist claims: firstly the suggested impossibility for natural
      selection to be a cause acting upon populations and secondly the
      conceptualization that all evolutionary causes occur at the level of interactions
      between individual organisms. I argue that deriving the latter from the former
      involves supplementary assumptions concerning precisely what causation is. I
      critically examine two of these assumptions purportedly preventing natural
      selection being regarded as a cause: the locality claim and the modularity claim.
      I conclude that justifying the strongest version of statisticalism-i.e.
      evolutionary causation only occurs at the level of individual interactions
      between organisms-would require further metaphysical arguments that are likely to
      be deemed highly problematic. Additionally, I argue that such a metaphysical
      position would be considered incongruous with both our scientific and ordinary
      use of the concepts of causality and explanation as employed within our everyday
      epistemological framework. 

PMID- 24140017
TI  - Splenic artery aneurysm: an important cause of hemoperitoneum and shock.
AB  - BACKGROUND: Splenic artery aneurysm ruptures are rare and highly morbid events
      that are frequently associated with pregnancy. However, approximately 15% may
      occur in men, and it is important to have this possibility in the differential
      diagnosis in cases of hemoperitoneum and hemorrhagic shock. Rapid diagnosis and
      treatment is essential to survival. OBJECTIVES: The aim of this report is to
      educate emergency physicians on the early recognition and treatment of this life
      threatening event and to increase the awareness of this condition in male
      patients. CASE REPORT: We describe the evaluation and management of two cases of
      splenic artery rupture in male patients with unique presentations. CONCLUSION:
      Splenic artery aneurysm ruptures should be considered in the differential
      diagnosis in any patient with undifferentiated shock. Early diagnosis and
      treatment can save lives.

PMID- 24140018
TI  - Reflect urine culture cancellation in the emergency department.
AB  - BACKGROUND: The yield of urine culture testing in the emergency department (ED)
      is often low, resulting in wasted laboratory and ED resources. Use of a reflex
      culture cancellation protocol, in which urine cultures are canceled when
      automated urinalysis results predict that culture yield will be low, may help to
      conserve these resources. STUDY OBJECTIVES: To identify a reflex culture
      cancellation protocol consisting of urinalysis-based criteria to limit urine
      culture over-utilization. METHODS: We studied patients aged 5 years and older
      whose ED evaluation included both an automated urinalysis and urine culture.
      Logistic regression models incorporating individual urinalysis components were
      used to predict culture growth. Receiver operating characteristic curves
      corresponding to each model were constructed, and the area under the curve was
      used to identify the model that best predicted positive urine culture growth.
      RESULTS: There were 1546 ED patients who met study inclusion criteria. Of these,
      314 (20%) had positive urine cultures. Restriction of culture testing to samples
      with white blood cells > 10 per high-power field, positive nitrites, positive
      leukocyte esterase, or positive bacteria provided a sensitivity of 96.5% (95%
      confidence interval [CI] 93.6-98.1%) and specificity of 48.1% (95% CI 45.3-51.0%)
      for positive urine culture. Implementation of a reflex culture cancellation
      protocol based on these criteria would have eliminated 604 of 1546 cultures
      (39%); 11 of 314 positive cultures (3.5%) would have been missed. CONCLUSION:
      These results suggest that a substantial reduction in urine culture testing might
      be achievable by implementing this protocol. Confirmation of these findings in a
      validation cohort is necessary.

PMID- 24140019
TI  - Letter to the editor.

PMID- 24140020
TI  - mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO
      acetylation and upregulation of c-Myc.
AB  - Aerobic glycolysis (the Warburg effect) is a core hallmark of cancer, but the
      molecular mechanisms underlying it remain unclear. Here, we identify an
      unexpected central role for mTORC2 in cancer metabolic reprogramming where it
      controls glycolytic metabolism by ultimately regulating the cellular level of c
      Myc. We show that mTORC2 promotes inactivating phosphorylation of class IIa
      histone deacetylases, which leads to the acetylation of FoxO1 and FoxO3, and this
      in turn releases c-Myc from a suppressive miR-34c-dependent network. These
      central features of activated mTORC2 signaling, acetylated FoxO, and c-Myc levels
      are highly intercorrelated in clinical samples and with shorter survival of GBM
      patients. These results identify a specific, Akt-independent role for mTORC2 in
      regulating glycolytic metabolism in cancer. 

PMID- 24140021
TI  - Osteocytes regulate primary lymphoid organs and fat metabolism.
AB  - Osteocytes act as mechanosensors to control local bone volume. However, their
      roles in the homeostasis of remote organs are largely unknown. We show that
      ablation of osteocytes in mice (osteocyte-less [OL] mice) leads to severe
      lymphopenia, due to lack of lymphoid-supporting stroma in both the bone marrow
      and thymus, and complete loss of white adipose tissues. These effects were
      reversed when osteocytes were replenished within the bone. In contrast, neither
      in vivo supply of T cell progenitors and humoral factors via shared circulation
      with a normal parabiotic partner nor ablation of specific hypothalamic nuclei
      rescued thymic atrophy and fat loss in OL mice. Furthermore, ablation of the
      hypothalamus in OL mice led to hepatic steatosis, which was rescued by parabiosis
      with normal mice. Our results define a role for osteocytes as critical regulators
      of lymphopoiesis and fat metabolism and suggest that bone acts as a central
      regulator of multiple organs.

PMID- 24140023
TI  - Synchronous bilateral bronchial carcinoid diagnosed with combined dual tracer
      ((18)F-FDG and (68)Ga-DOTATOC) PET/CT scans.

PMID- 24140022
TI  - Ketone bodies as signaling metabolites.
AB  - Traditionally, the ketone body beta-hydroxybutyrate (betaOHB) has been looked
      upon as a carrier of energy from liver to peripheral tissues during fasting or
      exercise. However, betaOHB also signals via extracellular receptors and acts as
      an endogenous inhibitor of histone deacetylases (HDACs). These recent findings
      support a model in which betaOHB functions to link the environment, in this case
      the diet, and gene expression via chromatin modifications. We review the
      regulation and functions of ketone bodies, the relationship between ketone bodies
      and calorie restriction, and the implications of HDAC inhibition by the ketone
      body betaOHB in the modulation of metabolism and in diseases of aging. 

PMID- 24140024
TI  - Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography
      in diagnosis and management of pancreatic cancer; comparison with multidetector
      row computed tomography, magnetic resonance imaging and endoscopic
      ultrasonography.
AB  - OBJECTIVES: We aimed to analyze the contribution of (18)F-fluorodeoxyglucose
      positron emission tomography/computed tomography (FDG PET/CT) imaging to the
      diagnosis and management of pancreatic cancer compared with multidetector row
      computed tomography (MDCT), magnetic resonance imaging (MRI) and endoscopic
      ultrasonography (EUS). MATERIAL AND METHODS: We retrospectively scanned the data
      of 52 patients who were referred for FDG PET/CT imaging for evaluation of
      pancreatic lesions greater than 10mm. The diagnostic performances of 4 imaging
      methods and the impact of PET/CT on the management of pancreatic cancer were
      defined. RESULTS: Pancreatic adenocarcinoma was diagnosed in 33 of 52 patients
      (63%), 15 patients had benign diseases of pancreas (29%), and 4 patients were
      normal (8%). Sensitivity and NPV of EUS and PET/CT were equal (100%) and higher
      than MDCT and MRI. Specificity, PPV and NPV of PET/CT were significantly higher
      than MDCT. However, sensitivities of two imaging methods were not significantly
      different. There was no significant difference between PET/CT and MRI and EUS for
      these values. When the cut-off value of SUVmax was 3.2, the most effective
      sensitivity and specificity values were obtained. PET/CT contributed to the
      management of pancreatic cancer in 30% of patients. CONCLUSION: FDG PET/CT is a
      valuable imaging method for the diagnosis and management of pancreatic cancer,
      especially when applied along with EUS as first line diagnostic tools.

PMID- 24140025
TI  - A false positive finding on the PET of somatostatin receptor due to a
      chondromyxoid fibroma.

PMID- 24140027
TI  - Mathematical models for morphogenesis: linear or nonlinear diffusion: comment on
      "Morphogenetic action through flux-limited spreading" by Verbeni, Sanchez,
      Mollica, Siegl-Cachedenier, Carleton, Guerrero, Ruiz i Altaba, Soler.

PMID- 24140026
TI  - [Organization of mechanical ventilation in French Intensive care units].
AB  - OBJECTIVES: To clarify the procedures related to mechanical ventilation in the
      intensive care unit setting: allocation of ventilators, team education,
      maintenance and reference documents. STUDY DESIGN: Declarative survey. METHODS:
      Between September and December 2010, we assessed the assignment and types of
      ventilators (ICU ventilators, temporary repair ventilators, non-invasive
      ventilators [NIV], and transportation ventilators), medical and nurse education,
      maintenance of the ventilators, presence of reference documents. Results are
      expressed in median/range and proportions. RESULTS: Among the 62 participating
      ICUs, a median of 15 ventilators/ICU (range 1-50) was reported with more than one
      trademark in 47 (76%) units. Specific ventilators were used for NIV in 22 (35%)
      units, temporary repair in 49 (79%) and transportation in all the units. Nurse
      education courses were given by ICU physicians in 54 (87%) units or by a company
      in 29 (47%) units. Medical education courses were made by ICU senior physicians
      in 55 (89%) units or by a company in 21 (34%) units. These courses were organized
      occasionally in 24 (39%) ICU and bi-annually in 16 (26%) units. Maintenance
      procedures were made by the ICU staff in 39 (63%) units, dedicated staff (17
      [27%]) or bioengineering technicians (14 [23%] ICU). Reference documents were
      written for maintenance procedures in 48 (77%) units, ventilator setup in 22
      (35%) units and ventilator dysfunction in 20 (32%) ICU. CONCLUSIONS: This first
      survey shows disparate distribution of ventilators and practices among French
      ICU. Education and understanding of the proper use of ventilators are key issues
      for security improvement.

PMID- 24140028
TI  - Spontaneous occlusion of the frontal arteriovenous malformation and the following
      progression of the associated aneurysm: a case report.
AB  - We report the case of a 59-year-old women with a cerebral arteriovenous
      malformation (AVM) in the right frontal lobe, which was detected incidentally.
      Additionally, an aneurysm was found at the feeding artery of the AVM. The patient
      was treated conservatively. Nine years later, the nidus of the AVM was no longer
      detectable. The angiography showed the associated aneurysm growing irregularly
      with a daughter sac. The spontaneous occlusion of an AVM and the following
      progression of an associated aneurysm are rare. The possible mechanisms leading
      to the occlusion of the AVM and the progression of the associated aneurysm are
      discussed. 

PMID- 24140029
TI  - Multilocus phylogeny of talpine moles (Talpini, Talpidae, Eulipotyphla) and its
      implications for systematics.
AB  - The tribe Talpini is a group of strictly subterranean moles distributed across
      the Eurasian Continent whose phylogenetic relationships and taxonomy remain
      unresolved. Here we report a multi-locus nuclear-mitochondrial DNA dataset (9468
      bp) from 11 talpine species encompassing all five recognized genera, together
      with analyses of their divergence times and evolutionary affinities inferred from
      maximum likelihood and Bayesian approaches. Our results finely resolved all
      relationships except the root of the four recognized Asian genera, which was
      placed sister to the genus Talpa. With respect to the Asian clade, we moreover
      provide the first molecular support for a sister-taxon relationship between
      Parascaptor and Scaptochirus and confirm that the genus Euroscaptor is
      paraphyletic. Further, and despite a relatively small sample size (22 specimens),
      our species delimitation analyses support the existence of at least two
      genetically distinct, and hence potentially cryptic species. Taken together,
      these findings argue that generic status should be given to E. mizura and
      illustrate that the taxonomic diversity of the tribe Talpini in mountainous
      regions of southwestern China and Southeast Asia is underestimated. Finally,
      results of our divergence time analyses support a rapid radiation of the endemic
      Asian genera in the late-Miocene, which temporally corresponds with enhanced
      aridity and cooling arising from a significant uplift of the Himalayan-Tibetan
      plateau.

PMID- 24140030
TI  - Sustained virological response to antiviral treatment in chronic hepatitis C
      patients may be predictable by HCV-RNA clearance in peripheral blood mononuclear
      cells.

PMID- 24140031
TI  - No detection of the NS5B S282T mutation in treatment-naive genotype 1 HCV/HIV-1
      coinfected patients using deep sequencing.
AB  - BACKGROUND: The S282T mutation is the main variant described associated with
      resistance to nucleos(t)ide analogues hepatitis C virus (HCV) NS5B polymerase
      inhibitors. OBJECTIVE: We aimed here to investigate whether this substitution pre
      existed in treatment naive HCV/HIV-1 coinfected patients. STUDY DESIGN: NS5B
      polymerase deep sequencing was performed at a median coverage per base of 4471 in
      16 patient samples. RESULTS: No S282T variant was detected in the 16 analyzed
      samples. CONCLUSION: This finding is in agreement with the high genetic barrier
      of nucleoside analogues NS5B polymerase inhibitors and the clinical efficacy of
      these compounds.

PMID- 24140032
TI  - Chronic hepatitis E infection cured by pregnancy.

PMID- 24140033
TI  - Subcutaneous progesterone versus vaginal progesterone gel for luteal phase
      support in in vitro fertilization: a noninferiority randomized controlled study.
AB  - OBJECTIVE: To compare the safety, efficacy, and tolerability of subcutaneous
      progesterone (Prolutex, 25 mg; IBSA Institut Biochimique SA) with vaginal
      progesterone gel (Crinone, 8%; Merck Serono) for luteal phase support (LPS) in
      assisted reproduction technologies (ART) patients. DESIGN: Prospective, open
      label, randomized, controlled, parallel-group, multicenter, two-arm,
      noninferiority study. SETTING: Thirteen European fertility clinics. PATIENT(S): A
      total of 683 ART patients randomized to two groups: Prolutex, 25 mg
      subcutaneously daily (n = 339); and Crinone, 90 mg 8% gel daily (n = 344).
      INTERVENTION(S): In vitro fertilization and embryo transfer were performed
      according to site-specific protocols. On the day of oocyte retrieval, Prolutex or
      Crinone gel was begun for LPS and continued for up to 10 weeks. MAIN OUTCOME
      MEASURE(S): Ongoing pregnancy rate. RESULT(S): The primary end point, ongoing
      pregnancy rates at 10 weeks of treatment were 27.4% and 30.5% in the Prolutex and
      Crinone groups, respectively (intention to treat [ITT]). The nonsignificant
      difference between the groups was -3.09% (95% confidence interval [CI] -9.91
      3.73), indicating noninferiority of Prolutex to Crinone. Delivery and live birth
      rates resulted to be equivalent between the two treatments (26.8% vs. 29.9% in
      the Prolutex and Crinone groups, respectively [ITT]; difference -3.10 [95% CI 
      9.87-3.68]). No statistically significant differences were reported for any of
      the other secondary efficacy endpoints, including comfort of usage and overall
      satisfaction. CONCLUSION(S): Implantation rate, pregnancy rate, live birth rate,
      and early miscarriage rate for Prolutex were similar to those for Crinone. The
      adverse event profiles were similar and Prolutex was safe and well tolerated.
      CLINICAL TRIAL REGISTRATION NUMBER: NCT00827983.

PMID- 24140034
TI  - Danish sperm donors across three decades: motivations and attitudes.
AB  - OBJECTIVE: To study the motivation and attitudes toward donor anonymity, economic
      compensation, and insemination of lesbian and single women among Danish sperm
      donors in 2012 compared with the two preceding decades. DESIGN: Anonymous survey.
      SETTING: Danish sperm bank. PATIENT(S): Sperm donors active in 2012 (n = 97),
      2002 (n = 62), and 1992 (n = 41). INTERVENTION(S): All donors who donated sperm
      in the study period were asked to participate. The results were compared with
      those of previous surveys from the same sperm bank. MAIN OUTCOME MEASURE(S):
      Motivation and attitudes toward donor anonymity, economic compensation, and
      insemination of lesbian and single women. RESULT(S): In 2012, the most frequently
      stated factor was altruism, motivating 90% of the sperm donors, which was not
      significantly different from the previous surveys. If economic compensations were
      removed, only 14% would continue to donate. The proportion of anonymous donors
      who would stop their donations if anonymity was abolished was 51%, 56%, and 67%
      in 1992, 2002, and 2012, respectively. A significantly increasing proportion of
      donors felt positive about donation to lesbian couples. CONCLUSION(S): The
      motivation for sperm donation is multifaceted and primarily based on economic
      compensation and altruism. Most Danish donors would stop their donations if
      economic compensation or anonymity were abolished.

PMID- 24140035
TI  - Diagnostic accuracy of sperm chromatin dispersion test to evaluate sperm
      deoxyribonucleic acid damage in men with unexplained infertility.
AB  - OBJECTIVE: To compare the sperm chromatin dispersion (SCD) test and the terminal
      uridine nick-end labeling (TUNEL) assay for assessment of sperm DNA damage.
      DESIGN: Prospective comparative experimental study. SETTING: Andrology
      laboratory. PATIENT(S): Twenty subfertile men with unexplained infertility.
      INTERVENTION(S): Sperm DNA damage was determined in the same semen samples using
      the TUNEL assay with fluorescence microscopy and the SCD test with bright-field
      microscopy. MAIN OUTCOME MEASURE(S): Correlation coefficient and receiver
      operating characteristic analysis outcomes. The TUNEL assay was used as the
      reference standard to identify optimal cutoff points for assessing DNA damage by
      SCD. RESULT(S): The SCD test detected a significantly higher proportion of sperm
      with damaged DNA (20.6% +/- 14.0%) than the TUNEL assay (11.5% +/- 7.3%).
      Spearman's rank correlation showed that the methods were not comparable (r =
      0.29). Receiver operating characteristic analysis revealed that 15% was the best
      SCD cutoff point to classify patients within the same levels of DNA
      fragmentation, normal or abnormal, as determined by the TUNEL assay, with an
      accuracy of 69%. CONCLUSION(S): The SCD test is more sensitive than the TUNEL
      assay for the assessment of DNA damage in men with unexplained infertility.
      Although the methods are poorly correlated, SCD may discriminate men with normal
      and abnormal sperm DNA damage with moderate accuracy when compared with TUNEL. It
      is important to distinguish between the methods because they differently evaluate
      sperm DNA damage.

PMID- 24140036
TI  - A new approach to evaluate aging effects on human oocytes: Fourier transform
      infrared imaging spectroscopy study.
AB  - OBJECTIVE: To characterize from a vibrational point of view the alterations
      caused by aging on human oocytes. DESIGN: Reproductive biology. SETTING: Private
      assisted reproductive technology clinic, synchrotron beam line, and university
      infrared laboratory. PATIENT(S): Twenty women of different ages (30 +/- 2 and 39
      +/- 2 years) selected on the basis of detailed inclusion criteria and submitted
      to controlled ovarian stimulation according to a specific protocol.
      INTERVENTION(S): Collection of 68 supernumerary oocytes that were not used during
      the IVF cycle from the above cited consenting patients. MAIN OUTCOME MEASURE(S):
      Focal Plane Array Fourier transform infrared (FTIR) analysis of human oocytes.
      RESULT(S): Specific spectral differences were highlighted in the two experimental
      groups of oocytes. In particular, in oocytes of 39-year-old women, the occurrence
      of peroxidative processes and a decrease in the amount of carbohydrates were
      observed, together with alterations in the phospholipid membrane, proteic
      pattern, and nucleic acids content. CONCLUSION(S): For the first time, FTIR
      spectroscopy was applied to human oocytes, leading to strong evidence of damage
      from aging in the gametes of mature women, which could be related to a decline in
      reproductive function. All the information obtained may be considered useful to
      improve the scientific knowledge on human reproduction and to exploit new
      strategies for detecting oocyte aging.

PMID- 24140037
TI  - Oocyte donors' comprehension as assessed by the EDICT (Egg Donor Informed Consent
      Tool).
AB  - OBJECTIVE: To assess oocyte donors' comprehension of the process and potential
      risks of oocyte donation using the EDICT (Egg Donor Informed Consent Tool).
      DESIGN: Prospective cohort study. SETTING: University-based, tertiary
      reproductive health practice. PATIENT(S): Prospective oocyte donors.
      INTERVENTION(S): Donors (N = 65) participated in an audiovisual informational
      session, and met with a reproductive endocrinologist individually. Donors then
      completed the Subjective EDICT and Objective EDICT. MAIN OUTCOME MEASURE(S): We
      report scores on Subjective and Objective EDICT, scores stratified for
      demographic variables, relationship between Subjective and Objective EDICT
      scores, and the effect of counseling on scores. RESULT(S): In general, our cohort
      of oocyte donors performed well on both objective and subjective portions of the
      EDICT. We verified the effect of counseling on EDICT scores by comparing before
      and after counseling scores and demonstrating significant gains. There was no
      significant correlation between Subjective and Objective EDICT scores.
      CONCLUSION(S): For the first time, we report oocyte donors' comprehension of
      oocyte donation as assessed by the EDICT. Reassuringly, we demonstrate that
      oocyte donors have adequate subjective and objective comprehension of the process
      and risks associated with oocyte donation. We also demonstrate that oocyte donor
      comprehension is significantly impacted by physician counseling efforts. In
      addition, scores on perceived understanding (Subjective EDICT) did not predict
      scores on performance-based comprehension (Objective EDICT). The lack of
      correlation between the two scores further underscores the utility of a
      performance-based tool, as relying on a donor's self-report (e.g., simply signing
      a consent form to indicate understanding) may not reflect her actual
      understanding.

PMID- 24140038
TI  - Impact of induced pregnancies in the obstetrical outcome of twin pregnancies.
AB  - OBJECTIVE: To compare obstetric outcomes of induced twins with those
      spontaneously conceived. DESIGN: A prospective observational study was conducted
      in twin pregnancies delivered over 16 years. SETTING: A tertiary obstetric center
      with differentiated perinatal support. PATIENT(S): A total of 180 induced twins
      and 698 spontaneously conceived were included. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Comparison of demographic factors, obstetrical complications,
      gestational age at delivery, mode of delivery, birth weight, and immediate
      newborn outcome. RESULT(S): First-trimester bleeding was higher in the induced
      group (6.0% vs. 12.2%), as were gestational diabetes (4.4% vs. 8.3%) and
      discordant intrauterine growth (4.3% vs. 11.1%). Preterm premature rupture of
      membranes was less frequent (23.9% vs. 12.8%) as was preterm delivery <=32 weeks
      (22.5% vs. 14.0%). Cesarean section rate was higher (50.6% vs. 63.9%). Other
      obstetrical complications, newborn data, and puerperal complications were not
      statistically different. Except for first-trimester bleeding (significantly
      associated with monochorionicity), these results were independent from
      chorionicity. Regarding the induced method (ovulation induction, IVF, or ICSI),
      IVF is a predictor for first-trimester bleeding and IVF or ICSI a predictor for
      cesarean section. CONCLUSION(S): The higher rates found with induced twins of
      first-trimester bleeding, gestational diabetes, and discordant growth do not
      contribute to different neonatal immediate outcomes and do not contribute to
      higher rates of prematurity, low birth weight, or other major perinatal
      complications.

PMID- 24140039
TI  - What is the quality of information on social oocyte cryopreservation provided by
      websites of Society for Assisted Reproductive Technology member fertility
      clinics?
AB  - OBJECTIVE: To evaluate adequacy and adherence to American Society for
      Reproductive Medicine (ASRM) guidelines of internet information provided by
      Society for Assisted Reproductive Technology (SART)-affiliated clinics regarding
      social oocyte cryopreservation (SOC). DESIGN: Systematic evaluation of websites
      of all SART member fertility clinics. SETTING: The internet. PATIENT(S): None.
      INTERVENTION(S): All websites offering SOC services were scored using a 0-13
      scale, based on 10 questions designed to assess website quality and adherence to
      the ASRM/SART guidelines. The websites were analyzed independently by two
      authors. Whenever disagreement occurred, a third investigator determined the
      score. MAIN OUTCOME MEASURE(S): Scores defined website quality as excellent, >=9;
      moderate, 5-8; or poor, <=4 points. RESULT(S): Of the 387 clinics registered as
      SART members, 200 offered oocyte cryopreservation services for either medical or
      social reasons; 147 of these advertised SOC. The average website scores of those
      clinics offering SOC was 3.4 +/- 2.1 (range, 2-11) points. There was no
      significant difference in scores between private versus academic clinics or
      clinics performing more or less than 500 cycles per year. CONCLUSION(S): The
      majority of the websites do not follow the SART/ASRM guidelines for SOC,
      indicating that there is a need to improve the type and quality of information
      provided on SOC by SART member websites.

PMID- 24140040
TI  - MicroRNA expression profiles in human testicular tissues of infertile men with
      different histopathologic patterns.
AB  - OBJECTIVE: To investigate the expression profiles of microRNA (miRNA) in human
      testes showing different histopathological patterns. DESIGN: Microarray with
      quantitative real-time polymerase chain reaction (qRT-PCR) validation. SETTING:
      University research and clinical institutes. PATIENT(S): Azoospermic men who
      underwent testicular biopsy for sperm recovery in preparation for
      intracytoplasmic sperm injection. INTERVENTION(S): Testicular biopsies. MAIN
      OUTCOME MEASURE(S): Statistically significantly altered miRNA expression profiles
      among the testicular histopathologic patterns groups compared with normal pattern
      group. RESULT(S): According to miRNA array, a total of 197, 68, and 46 miRNAs
      were found to be differentially expressed when comparing the samples from Sertoli
      cell only (SCO), mixed atrophy (MA), and germ cell arrest (GA) groups,
      respectively, with normal spermatogenesis (N). Five miRNAs have been validated
      using qRT-PCR, and the results were consistent with miRNA array analysis.
      Bioinformatics analysis showed that five microRNAs (hsa-mir-34b*, hsa-mir-34b,
      hsa-mir-34c-5p, hsa-mir-449a, and hsa-mir-449b*) were involved in apoptosis, cell
      proliferation, and differentiation. Notably, potential target genes of these five
      miRNAs were involved in the spermatogenesis process. CONCLUSION(S): This study
      provides new insights into specific miRNAs that are expressed in infertile men
      with different histopathologic patterns, suggesting a role of miRNAs in
      regulating male germ and somatic cells and that their alteration is associated
      with reproductive abnormalities.

PMID- 24140041
TI  - Zwitterionic polymer-coated immunobeads for blood-based cancer diagnostics.
AB  - Both total plasma and tumor-derived microvesicle (TMV)-associated miRNAs have
      been proposed as potential blood-based biomarkers for cancer diagnosis. However,
      there has been no comparison of the two types of miRNAs for biomarker discovery
      because of technological challenges of isolating TMVs from human plasma. The
      effective isolation of TMVs can be hardly achieved with conventional immunobead
      based methods due to the high content of plasma proteins. In the current study,
      zwitterionic sulfobetaine-conjugated immunobeads are prepared using cluster of
      differentiation 83 (CD83) as a candidate protein marker for breast cancer-derived
      microvesicles. The zwitterionic immunobeads are more than 10-fold efficient for
      isolating TMVs from clinical plasma samples by suppressing nonspecific protein
      binding than conventional immunobeads. Early-stage breast cancer can be
      distinguished from benign breast disease by using the sulfobetaine-modified
      immunobeads, whereas conventional immunobeads show poor discriminatory
      performance. Further, we demonstrate that miRNAs in the form of TMVs offer a
      major improvement over total plasma miRNAs for early cancer detection. The
      analyses of miRNA expression levels show that in total, 6 miRNAs are
      significantly upregulated in the CD83-positive microvesicles of breast cancer
      patients, whereas differential miRNA expression is not detected on using total
      plasma RNA. The results indicate that our zwitterionic immunobead platform may
      constitute a powerful tool to identify circulating biomarkers and open a new
      avenue for highly sensitive blood-based cancer diagnostics. 

PMID- 24140042
TI  - Vascularization and bone regeneration in a critical sized defect using 2-N,6-O
      sulfated chitosan nanoparticles incorporating BMP-2.
AB  - An ideal bone tissue engineering graft should have both excellent pro
      osteogenesis and pro-angiogenesis to rapidly realize the bone regeneration in
      vivo. To meet this goal, 2-N,6-O-sulfated chitosan (26SCS) based nanoparticle (S
      NP) was successfully developed and showed a dose-dependent enhancement on
      angiogenesis in vitro. For the repair of a critical sized defect in rabbit
      radius, we developed BMP-2 loaded S-NP (BMP-2/S-NP) with protein loading
      efficiency of 1.4 +/- 0.2% and fabricated a gelatin sponge (G) based implant
      loaded with BMP-2/S-NP (BMP-2/S-NP/G). This implant exerted a delivery of BMP-2
      with an initial burst release of 15.3 +/- 4.1% in first 24 h and a gradual
      release for 21 days to 77.8 +/- 3.6%. The in vitro ALP assay revealed that the
      activity of released BMP-2 from BMP-2/S-NP/G was maintained after 3-d and 7-d
      delivery and further enhanced after 14-d delivery compared with the original BMP
      2. Furthermore, the in vivo effects of BMP-2/S-NP/G on the bone regeneration and
      vessel formation in the critical sized defect (18 mm) of rabbit radius were
      investigated by synchrotron radiation-based micro-computed tomography (SRMUCT)
      imaging, three dimensional micro-computed tomographic (MUCT) imaging,
      histological analysis, immunohistochemistry and biomechanical measurement. Based
      on the results, both peripheral vessel and new vessel formation were
      significantly increased by the BMP-2/S-NP/G treatment, along with the bridged
      defects at as early as 2 weeks, the healed defects at 8 weeks and the reunion of
      bone marrow cavity at 12 weeks. The results indicated that both controlled
      release of active BMP-2 and favorable vascularization at the defect site
      contributed by BMP-2/S-NP/G played a crucial role in accelerating and promoting
      bone augmentation. This study suggests that BMP-2/S-NP/G demonstrates promise for
      vascularization and bone regeneration in clinical case of large defect.

PMID- 24140043
TI  - The effect of mechanical extension stimulation combined with epithelial cell
      sorting on outcomes of implanted tissue-engineered muscular urethras.
AB  - Urethral defects are common and frequent disorders and are difficult to treat.
      Simple natural or synthetic materials do not provide a satisfactory curative
      solution for long urethral defects, and urethroplasty with large areas of
      autologous tissues is limited and might interfere with wound healing. In this
      study, adipose-derived stem cells were used. These cells can be derived from a
      wide range of sources, have extensive expansion capability, and were combined
      with oral mucosal epithelial cells to solve the problem of finding seeding cell
      sources for producing the tissue-engineered urethras. We also used the synthetic
      biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome
      issues such as potential pathogen infections derived from natural materials (such
      as de-vascular stents or animal-derived collagen) and differing diameters.
      Furthermore, we used a bioreactor to construct a tissue-engineered epithelial
      muscular lumen with a double-layer structure (the epithelial lining and the
      muscle layer). Through these steps, we used an epithelial-muscular lumen built in
      vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral
      reconstruction was successfully achieved based on image analysis and histological
      techniques at different time points. This study provides a basis for the clinical
      application of tissue engineering of an epithelial-muscular lumen.

PMID- 24140044
TI  - Enhanced cytotoxicity to cancer cells by mitochondria-targeting MWCNTs containing
      platinum(IV) prodrug of cisplatin.
AB  - Among the arsenal of nano-materials, carbon nanotubes (CNTs) are becoming more
      prominent due to favorable attributes including their unique shape, which
      promotes cellular-uptake, and large aspect-ratio that facilitates
      functionalization of bioactive molecules on their surface. In this study, multi
      walled carbon nanotubes (MWCNTs) were functionalized with either mitochondrial
      targeting fluorescent rhodamine-110 (MWCNT-Rho) or non-targeting fluorescein
      (MWCNT-Fluo). Despite structural similarities, MWCNT-Rho associated well with
      mitochondria (ca. 80% co-localization) in contrast to MWCNT-Fluo, which was
      poorly localized (ca. 21% co-localization). Additionally, MWCNT-Rho entrapping
      platinum(IV) pro-drug of cisplatin (PtBz) displayed enhanced potency (IC50 = 0.34
      +/- 0.07 MUM) compared to a construct based on MWCNT-Fluo (IC50 >= 2.64 MUM).
      Concurrently, preliminary in vitro toxicity evaluation revealed that empty MWCNT
      Rho neither decreased cell viability significantly nor interfered with
      mitochondrial membrane-potential, while seemingly being partially expelled from
      cells. Due to its targeting capability and apparent lack of cytotoxicity, MWCNT
      Rho complex was used to co-encapsulate PtBz and a chemo-potentiator, 3
      bromopyruvate (BP), and the resulting MWCNT-Rho(PtBz+BP) construct demonstrated
      superior efficacy over PtBz free drug in several cancer cell lines tested.
      Importantly, a 2-fold decrease in mitochondrial potential was observed, implying
      that mitochondrial targeting of compounds indeed incurred additional intended
      damage to mitochondria.

PMID- 24140046
TI  - Mussel-inspired hyperbranched poly(amino ester) polymer as strong wet tissue
      adhesive.
AB  - Current medical adhesives based on cyanoacrylates typically exhibit cellular
      toxicity. In contrast, fibrin adhesives are non-toxic but have poor adhesive
      properties. To overcome these drawbacks we designed a simple and scalable
      adhesive precursor inspired by marine mussel adhesion that functioned with strong
      adhesion in wet conditions and with low cytotoxicity. Dopamine, an-amine
      derivative of an amino acid abundantly present in mussel adhesive proteins, was
      co-polymerised with a tri-functional vinyl monomer, to form a hyperbranched
      poly(beta-amino ester) polymer termed poly(dopamine-co-acrylate) (PDA). A variety
      of molecular weights and crosslinking methods were analysed using an ex vivo
      porcine skin model and an almost 4 fold increase in wet adhesion strength was
      observed compared to TISSEEL((r)) fibrin sealant. With a fast curing time,
      degradable properties and low cytotoxicity, PDA is highly attractive for medical
      purposes and could have a broad impact on surgeries where surgical tissue
      adhesives, sealants, and haemostatic agents are used.

PMID- 24140047
TI  - Multifunctional polymer scaffolds with adjustable pore size and chemoattractant
      gradients for studying cell matrix invasion.
AB  - Transmigrating cells often need to deform cell body and nucleus to pass through
      micrometer-sized pores in extracellular matrix scaffolds. Furthermore,
      chemoattractive signals typically guide transmigration, but the precise interplay
      between mechanical constraints and signaling mechanisms during 3D matrix invasion
      is incompletely understood and may differ between cell types. Here, we used
      Direct Laser Writing to fabricate 3D cell culture scaffolds with adjustable pore
      sizes (2-10 MUm) on a microporous carrier membrane for applying diffusible
      chemical gradients. Mouse embryonic fibroblasts invade 10 MUm pore scaffolds even
      in absence of chemoattractant, but invasion is significantly enhanced by knockout
      of lamin A/C, a known regulator of cell nucleus stiffness. Nuclear stiffness thus
      constitutes a major obstacle to matrix invasion for fibroblasts, but chemotaxis
      signals are not essential. In contrast, epithelial A549 cells do not enter 10 MUm
      pores even when lamin A/C levels are reduced, but readily enter scaffolds with
      pores down to 7 MUm in presence of chemoattractant (serum). Nuclear stiffness is
      therefore not a prime regulator of matrix invasion in epithelial cells, which
      instead require chemoattractive signals. Microstructured scaffolds with
      adjustable pore size and diffusible chemical gradients are thus a valuable tool
      to dissect cell-type specific mechanical and signaling aspects during matrix
      invasion.

PMID- 24140045
TI  - Sustained inhibition of neovascularization in vldlr-/- mice following
      intravitreal injection of cerium oxide nanoparticles and the role of the ASK1
      P38/JNK-NF-kappaB pathway.
AB  - Cerium oxide nanoparticles (nanoceria) are direct antioxidants; they inhibit
      pathological neovascularization following a single intravitreal injection into
      new born very low density lipoprotein receptor knockout (vldlr(-/-)) mice.
      However, the long-term therapeutic effects and mechanisms of nanoceria action on
      regression of the existing pathologic neovascularization in the eyes are unknown.
      We intravitreally injected P28 vldlr(-/-) mice and extended the endpoint for
      analysis until P70. The data demonstrate that nanoceria sustained their
      therapeutic function up to 6 weeks. Multiple parameters for nanoceria effects
      were examined including: regression of existing abnormal blood vessels, reduction
      of vascular leakage, down-regulation of the expression of vascular endothelial
      growth factor (VEGF), acrolein, glial fibrillary acidic protein (GFAP) and
      caspase 3 as well as up-regulation of the expression of rod- and cone-opsin
      genes. Regulation of ASK1-P38/JNK-NF-kappaB signaling pathway by nanoceria was
      investigated. Our data demonstrated that a single intravitreal injection of
      nanoceria in P28 vldlr(-/-) mice produced sustained regression of existing
      oxidative stress-induced neovascularizations, prevented blood vessel leakage and
      inhibited apoptosis via down-regulation of the ASK1-P38/JNK-NF-kappaB signaling
      pathway.

PMID- 24140048
TI  - A comparison of phenylketonuria with attention deficit hyperactivity disorder: do
      markedly different aetiologies deliver common phenotypes?
AB  - Phenylketonuria (PKU) is a well-defined metabolic disorder arising from a
      mutation that disrupts phenylalanine metabolism and so produces a variety of
      neural changes indirectly. Severe cognitive impairment can be prevented by
      dietary treatment; however, residual symptoms may be reported. These residual
      symptoms appear to overlap a more prevalent childhood disorder: Attention
      Deficit/Hyperactivity Disorder (ADHD). However, the aetiology of ADHD is a vast
      contrast to PKU: it seems to arise from a complex combination of genes; and it
      has a substantial environmental component. We ask whether these two disorders
      result from two vastly different genotypes that converge on a specific core
      phenotype that includes similar dysfunctions of Gray's (Gray, 1982) Behavioural
      Inhibition System (BIS), coupled with other disorder-specific dysfunctions. If
      so, we believe comparison of the commonalities will allow greater understanding
      of the neuropsychology of both disorders. We review in detail the aetiology,
      treatment, neural pathology, cognitive deficits and electrophysiological
      abnormalities of PKU; and compare this with selected directly matching aspects of
      ADHD. The biochemical and neural pathologies of PKU and ADHD are quite distinct
      in their causes and detail; but they result in the disorder in the brain of large
      amino acid levels, dopamine and white matter that are very similar and could
      explain the overlap of symptoms within and between the PKU and ADHD spectra. The
      common deficits affect visual function, motor function, attention, working
      memory, planning, and inhibition. For each of PKU and ADHD separately, a subset
      of deficits has been attributed to a primary dysfunction of behavioural
      inhibition. In the case of ADHD (excluding the inattentive subtype) this has been
      proposed to involve a specific failure of the BIS; and we suggest that this is
      also true of PKU. This accounts for a substantial proportion of the parallels in
      the superficial symptoms of both disorders and we see this as linked to
      prefrontal, rather than more general, dysfunction of the BIS. 

PMID- 24140050
TI  - Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo
      syndrome: a systematic review of the literature to date.
AB  - Takotsubo syndrome (TS), also known as broken heart syndrome and neurogenic
      stunned myocardium, is an acute cardiac disease entity characterized by a
      clinical picture mimicking that of an acute coronary syndrome. The pathogenesis
      of TS has not been established yet. Among the most often debated pathologic
      mechanisms of TS are as follows: first, multi-vessel coronary spasm; second,
      myocardial microvascular dysfunction; third, aborted myocardial infarction caused
      by transient thrombotic occlusion of a long wrap-around left anterior descending
      artery; fourth, left ventricular outflow tract obstruction; fifth, blood-borne
      catecholamine cardiac toxicity; and sixth, cardiac sympathetic disruption and
      norepinephrine seethe and spillover. The aim of this review is to provide a
      thorough analysis of the literature data coming mainly from the neurological
      literature and dealing with the pathogenesis of TS. Substantial evidence
      challenging the first five hypotheses and arguing in favor of the hypothesis that
      acute cardiac sympathetic eruption and norepinephrine seethe and spillover is
      causing TS in predisposed patients is presented. 

PMID- 24140051
TI  - A monoclonal antibody targeting a highly conserved epitope in influenza B
      neuraminidase provides protection against drug resistant strains.
AB  - All influenza viral neuraminidases (NA) of both type A and B viruses have only
      one universally conserved sequence located between amino acids 222-230. A
      monoclonal antibody against this region has been previously reported to provide
      broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory
      effect against influenza B viral NA remained unknown. Here, we report that the
      monoclonal antibody provides a broad inhibition against various strains of
      influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the
      growth and NA enzymatic activity of two drug resistant influenza B strains (E117D
      and D197E) are also inhibited by the antibody even though these two mutations are
      conformationally proximal to the universal epitope. Collectively, these data
      suggest that this unique, highly-conserved linear sequence in viral NA is exposed
      sufficiently to allow access by inhibitory antibody during the course of
      infection; it could represent a potential target for antiviral agents and vaccine
      induced immune responses against diverse strains of type B influenza virus. 

PMID- 24140049
TI  - The effects of early-life seizures on hippocampal dendrite development and later
      life learning and memory.
AB  - Severe childhood epilepsy is commonly associated with intellectual developmental
      disabilities. The reasons for these cognitive deficits are likely multifactorial
      and will vary between epilepsy syndromes and even among children with the same
      syndrome. However, one factor these children have in common is the recurring
      seizures they experience - sometimes on a daily basis. Supporting the idea that
      the seizures themselves can contribute to intellectual disabilities are
      laboratory results demonstrating spatial learning and memory deficits in normal
      mice and rats that have experienced recurrent seizures in infancy. Studies
      reviewed here have shown that seizures in vivo and electrographic seizure
      activity in vitro both suppress the growth of hippocampal pyramidal cell
      dendrites. A simplification of dendritic arborization and a resulting decrease in
      the number and/or properties of the excitatory synapses on them could help
      explain the observed cognitive disabilities. There are a wide variety of
      candidate mechanisms that could be involved in seizure-induced growth
      suppression. The challenge is designing experiments that will help focus research
      on a limited number of potential molecular events. Thus far, results suggest that
      growth suppression is NMDA receptor-dependent and associated with a decrease in
      activation of the transcription factor CREB. The latter result is intriguing
      since CREB is known to play an important role in dendrite growth. Seizure-induced
      dendrite growth suppression may not occur as a single process in which pyramidal
      cells dendrites simply stop growing or grow slower compared to normal neurons.
      Instead, recent results suggest that after only a few hours of synchronized
      epileptiform activity in vitro dendrites appear to partially retract. This acute
      response is also NMDA receptor dependent and appears to be mediated by the
      Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the
      staging of seizure-induced growth suppression and the underlying molecular
      mechanisms will likely prove crucial for developing therapeutic strategies aimed
      at ameliorating the intellectual developmental disabilities associated with
      intractable childhood epilepsy.

PMID- 24140052
TI  - Topographical analysis of As-induced folding of alpha-MT1a.
AB  - Metallothionein binds multiple metals into two clustered domains. While the
      structure of the fully metalated protein is well known for the Cd- and Zn
      containing protein, there is little known about the structures of the metal-free
      protein (apo-metallothionein) and even less about the partially metalated forms.
      However, the partially-metalated species are vitally important intermediates in
      the passage of the protein from translational synthesis to its homeostatic buffer
      or metal chaperone roles. Because multiple metals bind to metallothioneins, the
      partially-metalated species span a wide range depending on the metal bound. Up to
      3 As(3+) bind stepwise to the alpha-domain fragment in a manner that allows
      measurement of each of the 4 species simultaneously with the number of free
      cysteines diminishing by 3 for every As(3+) bound: apo- (11 Cys), As1- (8 Cys),
      As2- (5 Cys) and As3-alpha-MT (2 Cys). The cysteine modifier benzoquinone (Bq),
      was used to determine the relative accessibility of the free cysteines in the
      alpha-MT fragment as a function of the number of As(3+) bound. The effect of each
      As(3+) was to induce folding in the protein. The ESI-MS results show that the
      whole protein folds significantly even when just one of the three As(3+) has
      bound. The profile of the Bq reacting with the unbound cysteines shows effects of
      steric hindrance in slowing down the reaction. By freezing the reaction midway to
      the endpoint, the mass spectral data show the 'mid-flight' concentrations of all
      the key species, 27 in all. Analysis of this mid-flight reaction profile gives
      insight into the topology of the partially metalated MT from the differential
      access to the unbound cysteinyl thiols by the Bq. Significantly, the metal-free,
      apo-alpha-MT also adopts a folded structure in the presence of the As(3+) even
      though there is no As(3+) bound. This can only happen if the apo-protein wraps
      around other metalated proteins in solution via protein-protein interactions. 

PMID- 24140053
TI  - Mechano-growth factor induces migration of rat mesenchymal stem cells by altering
      its mechanical properties and activating ERK pathway.
AB  - Mechano-growth factor (MGF) generated by cells in response to mechanical
      stimulation has been identified as a mechano effector molecule, playing a key
      role in regulating mesenchymal stem cell (MSC) function, including proliferation
      and migration. However, the mechanism(s) underlying how MGF-induced MSC migration
      occurs is still unclear. In the present study, MGF motivated migration of rat
      MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF
      at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably,
      enhancement of mechanical properties that is pertinent to cell migration, such as
      cell traction force and cell stiffness were found to respond to MGF treatment.
      Furthermore, MGF increased phosphorylation of extracellular signal-regulated
      kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and
      abolished MGF-induced rMSC migration were found, demonstrating that ERK is
      involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF
      induced rMSC migration and its direct link to altering rMSC mechanics and
      activating the ERK pathway, uncover the underlying biomechanical and biological
      mechanisms of MGF-induced rMSC migration, which may help find MGF-based
      application of MSC in clinical therapeutics.

PMID- 24140054
TI  - Contribution of de novo synthesis of Galphas-proteins to 1-methyladenine
      production in starfish ovarian follicle cells stimulated by relaxin-like gonad
      stimulating substance.
AB  - In starfish, the peptide hormone gonad-stimulating substance (GSS) secreted from
      nervous tissue stimulates oocyte maturation to induce 1-methyladenine (1-MeAde)
      production by ovarian follicle cells. The hormonal action of GSS on follicle
      cells involves its receptor, G-proteins and adenylyl cyclase. However, GSS failed
      to induce 1-MeAde and cAMP production in follicle cells of ovaries during
      oogenesis. At the maturation stage, follicle cells acquired the potential to
      respond to GSS by producing 1-MeAde and cAMP. Adenylyl cyclase activity in
      follicle cells of fully grown stage ovaries was also stimulated by GSS in the
      presence of GTP. These activations depended on the size of oocytes in ovaries.
      The alpha subunit of Gs-proteins was not detected immunologically in follicle
      cells of oogenesis stage ovaries, although Galphai and Galphaq were detectable.
      Using specific primers for Galphas and Galphai, expression levels of Galphas in
      follicle cells were found to increase significantly as the size of oocytes in
      ovaries increased, whereas the mRNA levels of Galphai were almost constant
      regardless of oocyte size. These findings strongly suggest the potential of
      follicle cells to respond to GSS by producing 1-MeAde and cAMP is brought by de
      novo synthesis of Galphas-proteins.

PMID- 24140055
TI  - A novel TK-NOG based humanized mouse model for the study of HBV and HCV
      infections.
AB  - The immunodeficient mice transplanted with human hepatocytes are available for
      the study of the human hepatitis viruses. Recently, human hepatocytes were also
      successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)
      NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK
      NOG mice and urokinase-type plasminogen activator-severe combined
      immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally
      with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes.
      Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus
      (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte
      repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice
      correlated well with pre-transplantation serum ALT levels induced by ganciclovir
      treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected
      serum developed viremia irrespective of lower replacement index. In contrast,
      establishment of HCV viremia was significantly more frequent in TK-NOG mice with
      low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of
      mice spontaneously in early stage of viral infection experiment (8weeks after
      injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug
      treatment with entecavir or interferon were similar in both mouse models. TK-NOG
      mice thus useful for study of hepatitis virus virology and evaluation of anti
      viral drugs.

PMID- 24140056
TI  - Evolutionary aspects of the synuclein super-family and sub-families based on
      large-scale phylogenetic and group-discrimination analysis.
AB  - Over the last decade, many genetic studies have suggested that the synucleins,
      which are small, natively unfolded proteins, are closely related to Parkinson's
      disease and cancer. Less is known about the molecular basis of this role. A
      comprehensive analysis of the evolutionary path of the synuclein protein family
      may reveal the relationship between evolutionarily conserved residues and protein
      function or structure. The phylogeny of 252 unique synuclein sequences from 73
      organisms suggests that gamma-synuclein is the common ancestor of alpha- and beta
      synuclein. Although all three sub-families remain highly conserved, especially at
      the N-terminal, nearly 15% of the residues in each sub family clearly diverged
      during evolution, providing crucial guidance for investigations of the different
      properties of the members of the superfamily. His50 is found to be an alpha
      specific conserved residue (91%) and, based on mutagenesis, evolutionarily
      developed a secondary copper binding site in the alpha synuclein family.
      Surprisingly, this site is located between two well-known polymorphisms of alpha
      synuclein, E46K and A53T, which are linked to early-onset Parkinson's disease,
      suggesting that the mutation-induced impairment of copper binding could be a
      mechanism responsible for alpha-synuclein aggregation. 

PMID- 24140057
TI  - A rapid screening and production method using a novel mammalian cell display to
      isolate human monoclonal antibodies.
AB  - Antibody display methods are increasingly being used to produce human monoclonal
      antibodies for disease therapy. Rapid screening and isolation of specific human
      antibody genes are valuable for producing human monoclonal antibodies showing
      high specificity and affinity. In this report, we describe a novel mammalian cell
      display method in which whole human IgG is displayed on the cell surface of CHO
      cells. Cells expressing antigen-specific human monoclonal IgGs with high affinity
      on the cell surface after normal folding and posttranscriptional modification
      were screened using a cell sorter. The membrane-type IgG-expressing CHO cells
      were then converted to IgG-secreting cells by transfection with a plasmid coding
      Cre recombinase. This mammalian cell display method was applied to in vitro
      affinity maturation of monoclonal C9 IgG specific to the human high-affinity IgE
      receptor (FcepsilonRIalpha). The CDR3 of the C9 heavy chain variable region gene
      was randomly mutated and inserted into pcDNA5FRT/IgG. A C9 IgG (CDRH3r)
      expressing CHO cell display library consisting of 1.1*10(6) independent clones
      was constructed. IgG-displaying cells showing high reactivity to FcepsilonRIalpha
      antigen were screened by the cell sorter, resulting in the establishment of a CHO
      cell line producing with higher reactivity than the parent C9 IgG. 

PMID- 24140058
TI  - GRAB is a binding partner for the Rab11a and Rab11b GTPases.
AB  - Co-ordination of Rab GTPase function has emerged as a crucial mechanism in the
      control of intracellular trafficking processes in eukaryotic cells. Here, we show
      that GRAB/Rab3IL1 [guanine nucleotide exchange factor for Rab3A; RAB3A
      interacting protein (rabin3)-like 1], a protein that has previously be shown to
      act as a GEF (guanine nucleotide exchange factor) for Rab3a, Rab8a and Rab8b, is
      also a binding partner for Rab11a and Rab11b, but not the closely related Rab25
      GTPase. We demonstrate that exogenous expression of Rab11a and Rab11b shift
      GRAB's distribution from the cytoplasm onto membranes. We find that the
      Rab11a/Rab11b-binding region of GRAB lies within its carboxy-terminus, a region
      distinct from its GEF domain and Rab3a-binding region. Finally, we describe a
      GRAB deletion mutant (GRABDelta223-228) that is deficient in Rab11-binding
      ability. These data identify GRAB as a dual Rab-binding protein that could
      potentially link Rab3 and Rab11 and/or Rab8 and Rab11-mediated intracellular
      trafficking processes.

PMID- 24140059
TI  - Ginsenoside Rg3 improves cardiac mitochondrial population quality: mimetic
      exercise training.
AB  - Emerging evidence indicates exercise training could mediate mitochondrial quality
      control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3),
      one of the active ingredients in Panax ginseng, is well known in herbal medicine
      as a tonic and restorative agent. However, the molecular mechanism underlying the
      beneficial effects of Rg3 has been elusive. In the present study, we compared the
      effects of Rg3 administration with aerobic exercise on mitochondrial adaptation
      in cardiac muscle tissue of Sprague-Dawley (SD) rats. Three groups of SD rats
      were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise
      trained. Both aerobic exercise training and Rg3 supplementation enhanced
      peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1alpha) and
      nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The
      activation of PGC-1alpha led to increased mRNA levels of mitochondrial
      transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes
      were accompanied by increases in mitochondrial DNA copy number and complex
      protein levels, while activation of Nrf2 increased levels of phase II detoxifying
      enzymes, including nicotinamide adenine dinucleotide phosphate:quinone
      oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic
      exercise also enhanced mitochondrial autophagy pathway activity, including
      increased conversion of LC3-I to LC3-II and greater expression of beclin1 and
      autophagy-related protein 7 (ATG7), these effects of aerobic exercise are
      comparable to that of Rg3. These results demonstrate that Rg3 mimics improved
      cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and
      enhancing the quantity and quality of mitochondria. 

PMID- 24140060
TI  - Progesterone induces expression of Lrp2 in the murine uterus.
AB  - Progesterone (P4) and progesterone receptor (PR) have important functions in
      uterine environment. In previous studies, using high density DNA microarray
      analysis, we identified low density lipoprotein receptor-related protein 2 (Lrp2)
      is one of the genes upregulated by P4 and PR. In present studies, we examined the
      expression of Lrp2 through real-time PCR, in situ hybridization and
      immunohistochemistry by P4-PR response. Lrp2 mRNA transcript was significantly
      increased after P4 treatment in the luminal and glandular epithelium of the wild
      type mice. However, Lrp2 expression was not observed in the progesterone receptor
      knock out (PRKO) mice treated with P4. The expression of Lrp2 expression is not
      regulated by estrogen. During early pregnancy, the expression of Lrp2 was
      detected at 2.5 dpc and then significantly increased at 3.5 dpc in luminal and
      glandular epithelium. These results suggest that Lrp2 is a novel target gene by
      P4 and PR.

PMID- 24140061
TI  - Nucleostemin is indispensable for the maintenance and genetic stability of
      hematopoietic stem cells.
AB  - Nucleostemin is a nucleolar protein known to play a variety of roles in cell
      cycle progression, apoptosis inhibition, and DNA damage protection in embryonic
      stem cells and tissue stem cells. However, the role of nucleostemin in
      hematopoietic stem cells (HSCs) is yet to be determined. Here, we identified an
      indispensable role of nucleostemin in mouse HSCs. Depletion of nucleostemin using
      short hairpin RNA strikingly impaired the self-renewal activity of HSCs both in
      vitro and in vivo. Consistently, nucleostemin depletion triggered apoptosis
      rather than cell-cycle arrest in HSCs. Furthermore, DNA damage accumulated during
      cultivation upon depletion of nucleostemin. The impaired self-renewal activity of
      HSCs induced by nucleostemin depletion was partially rescued by p53 deficiency
      but not by p16(Ink4a) or p19(Arf) deficiency. Taken together, our study
      demonstrates that nucleostemin protects HSCs from DNA damage accumulation and is
      required for the maintenance of HSCs. 

PMID- 24140062
TI  - SIRT5 desuccinylates and activates SOD1 to eliminate ROS.
AB  - Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1
      is associated with various human diseases, including cancer. Here, we report that
      SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds
      to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased
      when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site
      inhibits the growth of lung tumor cells. These results reveal a novel post
      translational regulation of SOD1 by means of succinylation and SIRT5-dependent
      desuccinylation, which is important for the growth of lung tumor cells. 

PMID- 24140063
TI  - C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in
      glioblastoma multiforme cells.
AB  - The c-Myc oncogene is amplified in many tumor types. It is an important regulator
      of cell proliferation and has been linked to altered miRNA expression, suggesting
      that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR
      26a has been reported to be upregulated in glioblastoma multiforme (GBM), the
      mechanism has not been established. We have shown that ectopic expression of miR
      26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that
      is inactivated in many common malignancies, including GBM. Our findings suggest
      that c-Myc modulates genes associated with oncogenesis in GBM through
      deregulation of miRNAs via the c-Myc-miR-26a-PTEN signaling pathway. This may be
      of clinical relevance. 

PMID- 24140064
TI  - Time to positivity of blood culture is predictive for nosocomial infection and
      infectious endocarditis instead of other clinical characteristics and prognosis
      in Acintobacter baumannii bloodstream infection.

PMID- 24140065
TI  - Description and predictive factors of infection in patients with chronic kidney
      disease admitted to the critical care unit.
AB  - OBJECTIVES: To describe the spectrum of infection and multidrug-resistant
      bacterial colonization, and to identify early predictors of infection in patients
      with chronic kidney disease (CKD) admitted to the critical care unit (CCU).
      METHODS: A 7-month observational prospective single-centre study in a French
      university hospital. RESULTS: 791 patients were admitted to the CCU, 135 of whom
      (17%) had severe CKD. Among these, 41 (30%) were infected on admission. Infection
      was microbiologically documented in 32 patients (78%), of which 7 (22%) were
      related to Pseudomonas aeruginosa. There was no infection related to extended
      spectrum beta-lactamase-producing enterobacteriaceae despite a 12% carriage rate
      on admission. A temperature >=37.6  degrees C and a leukocyte count >12.000/mm3
      were specific but poorly sensitive of infection (91% and 80%, and 45% and 39%,
      respectively). Using the threshold of 0.85 ng/ml, procalcitonin was a strong
      independent predictor of infection on admission (OR 12.8, 95% CI 4.4-37.3). Age
      (>=60 years) and the cause of CKD were two other predictors. CONCLUSIONS:
      Infection accounts for one-third of CCU admissions in CKD patients, with a high
      prevalence of P. aeruginosa. The usual diagnostic criteria are inaccurate for
      diagnosing infection in this population. A procalcitonin >=0.85 ng/ml might be
      helpful for early identifying CKD patients with infection.

PMID- 24140066
TI  - The high burden of pneumonia on US emergency departments during the 2009
      influenza pandemic.
AB  - OBJECTIVES: During the 2009 influenza A (H1N1) pandemic, unusual influenza
      activity outside the typical winter season provided a unique opportunity to
      evaluate the association between influenza and pneumonia incidence. We sought to
      quantify the impact of the 2009 pandemic on the incidence of emergency department
      (ED) visits for pneumonia in the United States (US). METHODS: Using the
      Nationwide Emergency Department Survey, we estimated monthly counts and rates of
      excess all-cause pneumonia ED visits in the US attributable to the pandemic by
      comparing observed pneumonia ED visits during the pandemic (April 2009-March
      2010) to expected values modeled from the three prior years. RESULTS: The
      pandemic was associated with an excess of 180,560 pneumonia ED visits or 0.59
      excess pneumonia visits per 1000 US population (95% confidence interval: 0.55,
      0.62). These excess visits accounted for 7.0% of all pneumonia ED visits during
      the pandemic year. The greatest excess occurred during months with highest
      influenza activity (September-November 2009). Persons aged <65 years accounted
      for 94% of the excess pneumonia visits. CONCLUSIONS: ED visits for pneumonia
      increased substantially during the 2009 pandemic, especially during peak
      influenza activity, suggesting a strong association between influenza activity
      and pneumonia incidence during the pandemic period.

PMID- 24140067
TI  - Evaluation of the anti-infectious properties of polyester vascular prostheses
      functionalised with cyclodextrin.
AB  - OBJECTIVES: Synthetic vascular graft infection (SVGI) remains associated with
      high morbidity-mortality rates. Newly developed polyester vascular prostheses
      (PVP) functionalised with cyclodextrin (PVP-CD) allowed sustained-drug-eluting of
      several antibiotics. This study aimed to evaluate the efficacy of PVP-CD loaded
      with antibiotics against bacteria that are commonly responsible for SVGI in
      current practice. METHODS: Samples of PVP-CD loaded with antibiotics and uncoated
      PVP were tested in-vitro for their ability to limit bacterial adhesion and
      prevent bacterial proliferation over time. Their anti-infectious properties were
      further evaluated in-vivo in a mouse model of SVGI. Both Gram-positive
      (Staphylococcus aureus, Staphylococcus epidermidis, MRSA) and Gram-negative
      (Escherichia coli, En. cloacae and Pseudomonas aeruginosa) bacteria were tested.
      RESULTS: PVP-CD loaded with rifampin showed significant bacterial adhesion
      reduction and growth inhibition against Gram-positive bacteria. Similar results
      were obtained against Gram-negative bacteria with PVP-CD loaded with
      ciprofloxacin. In the mouse model, Gram-positive and Gram-negative bacterial
      proliferations were significantly prevented by PVP-CD loaded with rifampin or
      with ciprofloxacin respectively. A decrease in macroscopic infections correlated
      with the bacterial proliferation rates depicted on the samples (Spearman's rho =
      0.61; P < 0.0001). CONCLUSIONS: We have demonstrated the efficacy of PVP-CD
      loaded with appropriate antibiotics both in-vitro and in-vivo against six of the
      most common bacteria involved in human SVGI.

PMID- 24140068
TI  - Interleukin-32 contributes to invasion and metastasis of primary lung
      adenocarcinoma via NF-kappaB induced matrix metalloproteinases 2 and 9
      expression.
AB  - Interleukin (IL)-32 is a novel proinflammatory cytokine, which has been shown to
      play an important role in tumor growth and metastasis. Here, we discovered that
      IL-32 was aberrantly over-expressed in lung adenocarcinoma tissues and cell
      lines. Positive expression of IL-32 significantly correlated with the clinical
      staging, and lymph node and distant metastases. High expression of IL-32 was an
      independent indicator of poor prognosis in lung adenocarcinoma patients.
      Moreover, IL-32-facilitated cell migration and invasion in vitro was mediated
      through transactivation of the nuclear transcription factor (NF)-kappaB signaling
      pathway and subsequent upregulation of matrix metalloproteinase (MMP)-2 and MMP9
      expression. These studies demonstrate that IL-32 plays a role in the tumor
      associated inflammatory microenvironment and that overexpression of IL-32
      contributes to invasion and metastasis in primary lung adenocarcinoma, suggesting
      that it may have clinical utility as a prognostic biomarker and potential target
      for immunotherapy in lung adenocarcinoma. 

PMID- 24140069
TI  - Regulation of interferon lambda-1 (IFNL1/IFN-lambda1/IL-29) expression in human
      colon epithelial cells.
AB  - The efficient regulation of intestinal immune responses is critical to colon
      health. Viruses, for example noraviruses, are key pathogens of the intestine. The
      lambda interferons (comprising three ligands: IFNL1, L2 and L3 - the so-called
      "Type III" interferons) constitute the most recently discovered IFN family and
      are known to be important in intestinal anti-viral defense. A fourth family
      member, IFNL4, was recently described. Expression of the IFN-lambda receptor is
      restricted to epithelial and immune cells; together, these ligands and their
      receptor represent an important anti-viral and immunoregulatory component of the
      immune/epithelial inteface. We investigated control of IFNL1 expression in human
      colon epithelial cells. We used the TLR3 agonist poly I:C to drive expression of
      IFNL1 in SW480 cells, and small interfering RNA (siRNA) to knockdown target
      transcription factors. We identified ZEB1 and BLIMP-1 as transcription factors
      that strongly inhibited IFNL1 expression in SW480 cells. Interestingly, while
      BLIMP-1 inhibited both type-III and type-I interferons (IFN-beta), the inhibitory
      action of ZEB1 was specific for IFNL1. We also defined the NF-kappaB family
      member, p65 as a key activator of IFNL1 and NF-kappaB p50 as a key inhibitor.
      Finally, we demonstrated that siRNA targeting of ZEB1 or NF-kappaB p50 resulted
      in a significant elevation of secreted IFN-lambda1 protein and expression of the
      anti-viral gene OAS1, while knockdown of p65 inhibited these events. Our data
      provide insight to the regulation of IFNL1 expression in the human colon and
      suggest novel therapeutic approaches to elevate IFNlambda-1 protein where
      required. 

PMID- 24140070
TI  - Saliva collection by using filter paper for measuring cortisol levels in dogs.
AB  - Four experiments were conducted to evaluate the accuracy and reliability of
      noninvasive evaluation of cortisol in saliva of dogs. In experiment 1, we
      measured the cortisol concentration in the filter paper on which 250-MUL cortisol
      solutions had been quantitatively pipetted and in filter papers dipped in
      cortisol solution. In experiment 2, we collected the blood and saliva of dogs 3
      times at 30-min intervals and compared the cortisol concentrations to examine
      whether the dynamics of cortisol in the blood and saliva are similar. The results
      of experiments 1 and 2 showed that the cortisol concentration can be
      quantitatively measured with this method and that the dynamics of cortisol
      concentration in the plasma and saliva collected by using filter paper are not
      different (P = 0.14 for experiment 1 and P = 0.51 for experiment 2). In
      experiment 3, to investigate the factors related to inducing stress in dogs by
      using the filter-paper method of collecting saliva, we compared the cortisol
      concentrations at 0 and 30 min after collecting the saliva of pet dogs. The dog
      owners completed a survey on their dogs, providing basic information and
      reporting the collection of their dog's saliva. We found that the cortisol
      concentrations increased significantly in dogs whose owners spent >2 min
      collecting saliva (P = 0.005), suggesting that prompt collection of saliva is
      necessary for accurate assessment of cortisol without induction of a stress
      response. In addition, the cortisol concentrations increased significantly in
      dogs whose teeth were not regularly brushed (P = 0.04), suggesting that regular
      teeth brushing mitigates the effect of the collection process on cortisol
      concentrations in the saliva, with minimal stress to the dogs. In experiment 4,
      we measured cortisol concentrations in pet dogs accustomed to having their teeth
      brushed by their owners, before and after interaction with their owners, to
      assess whether brushing induces stress in dogs. We detected that the cortisol
      concentrations significantly decreased after human-dog interaction (P = 0.008),
      suggesting that this method does not induce stress in dogs. Our study indicates
      that the method of saliva collection by using filter paper is effective in
      measuring the cortisol concentrations to evaluate stress, although certain steps
      are required to enhance accuracy. 

PMID- 24140071
TI  - Immunosequencing: applications of immune repertoire deep sequencing.
AB  - Advances in high-throughput sequencing have enabled the development of a powerful
      new technology for probing the adaptive immune system. Millions of B or T cell
      receptor sequences can be read in parallel from a single sample. The dynamics of
      an adaptive immune response, which is based on clonal expansion and contraction,
      can be monitored in real time at high sensitivity and the global properties of
      the adaptive immune repertoires can be studied. A large set of clinical
      applications for this technology are presently under study, with a few diagnostic
      applications for hematological malignancies already available. A review of this
      new field termed immunosequencing is presented. 

PMID- 24140072
TI  - Electroencephalographic activity of preterm infants is increased by Family
      Nurture Intervention: a randomized controlled trial in the NICU.
AB  - OBJECTIVE: To assess the impact of Family Nurture Intervention (FNI) on
      electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation).
      METHODS: Two groups were tested in a single, level IV neonatal intensive care
      unit (NICU; standard care or standard care plus FNI) using a randomized
      controlled trial design. The intervention consists of sessions designed to
      achieve mutual calm and promote communication of affect between infants and their
      mothers throughout the NICU stay. EEG recordings were obtained from 134 infants
      during sleep at ~35 and ~40 weeks postmenstrual age (PMA). Regional brain
      activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each
      of 125 electrodes. RESULTS: Near to term age, compared to standard care infants,
      FNI infants showed robust increases in EEG power in the frontal polar region at
      frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were
      significant in both quiet and active sleep, regardless of gender, singleton-twin
      status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500
      g). CONCLUSION: FNI leads to increased frontal brain activity during sleep, which
      other investigators find predictive of better neurobehavioral outcomes.
      SIGNIFICANCE: FNI may be a practicable means of improving outcomes in preterm
      infants.

PMID- 24140073
TI  - Equilibrium contact angle or the most-stable contact angle?
AB  - It is well-established that the equilibrium contact angle in a thermodynamic
      framework is an "unattainable" contact angle. Instead, the most-stable contact
      angle obtained from mechanical stimuli of the system is indeed experimentally
      accessible. Monitoring the susceptibility of a sessile drop to a mechanical
      stimulus enables to identify the most stable drop configuration within the
      practical range of contact angle hysteresis. Two different stimuli may be used
      with sessile drops: mechanical vibration and tilting. The most stable drop
      against vibration should reveal the changeless contact angle but against the
      gravity force, it should reveal the highest resistance to slide down. After the
      corresponding mechanical stimulus, once the excited drop configuration is
      examined, the focus will be on the contact angle of the initial drop
      configuration. This methodology needs to map significantly the static drop
      configurations with different stable contact angles. The most-stable contact
      angle, together with the advancing and receding contact angles, completes the
      description of physically realizable configurations of a solid-liquid system.
      Since the most-stable contact angle is energetically significant, it may be used
      in the Wenzel, Cassie or Cassie-Baxter equations accordingly or for the surface
      energy evaluation. 

PMID- 24140074
TI  - Symptoms of disturbed sleep predict major adverse cardiac events after
      percutaneous coronary intervention.
AB  - BACKGROUND: Disturbed sleep is associated with atherosclerosis in native coronary
      arteries and may be associated with adverse cardiac events after percutaneous
      coronary intervention (PCI). We sought to determine the association between
      symptoms of disturbed sleep and adverse cardiovascular events after PCI. METHODS:
      Outpatients who were stable after successful PCI were assessed for symptoms of
      disturbed sleep with 10 true/false questions. Follow-up was performed at least 4
      years after PCI. The primary outcome was a composite of death, myocardial
      infarction (MI), and repeated revascularization. RESULTS: Three hundred eighty
      eight patients (mean age, 66 +/- 11 years) reported on average 3.1 +/- 2.1 sleep
      disturbance symptoms. Follow-up was performed on average 4.4 years after the
      incident PCI. The primary outcome occurred in 25% of patients. An association was
      seen between the number of sleep disturbance symptoms and the occurrence of the
      primary end point. Patients with zero symptoms had a 4-year event rate of 12%
      compared with a 67% event rate for those with 9 symptoms. On multivariable
      analysis, sleep symptoms, diabetes mellitus, and the number of diseased coronary
      vessels were independently associated with the primary end point. Each additional
      sleep symptom was associated with a hazard ratio (HR) of 1.2 (P = 0.001). The
      results were driven primarily by the association between symptoms of disturbed
      sleep and the need for repeated revascularization (repeated PCI HR, 1.9; P =
      0.003; coronary artery bypass grafting (CABG) HR, 1.5; P = 0.001). CONCLUSIONS:
      Symptoms of disturbed sleep were associated with increased risk of long-term
      adverse cardiovascular outcomes after successful PCI.

PMID- 24140075
TI  - Arteriovenous fistula formation after lead extraction.
AB  - The junction between the left brachiocephalic vein and the superior vena cava is
      a high-risk region during lead extraction. Venous laceration with hemodynamic
      collapse is the most feared complication arising in this region, but
      arteriovenous fistula formation after excimer laser extraction also has been
      reported. A case of arteriovenous fistula presenting 3 days after extraction with
      acute pulmonary edema is described. A continuous murmur was heard near the
      extraction site and invasive angiography demonstrated a left internal mammary
      artery to the brachiocephalic vein fistula, which was coiled. A new continuous
      murmur after lead extraction is the hallmark of this rare complication. 

PMID- 24140076
TI  - Adherence to blood pressure-lowering drugs and resistant hypertension: should
      trial of direct observation therapy be part of preassessment for renal
      denervation?
AB  - Renal denervation (RDN) is increasingly used for resistant hypertension. We
      report here a case of pseudoresistance of hypertension caused by nonadherence to
      prescribed drug therapy (6 medications), which evaded detection by verification
      of prescription filling. Direct observation therapy (DOT), in which usual
      antihypertensive medications are given under supervision, produced substantial
      reductions in blood pressure, which was subsequently controlled chronically with
      3 antihypertensive agents, confirming pseudoresistant hypertension. The novel
      teaching points are that evaluation of nonadherence to drug therapy is a crucial
      component in diagnosing resistant hypertension before RDN and that DOT may be
      extremely useful in avoiding an unnecessary and costly procedure. 

PMID- 24140077
TI  - Parabolic discounting of monetary rewards by physical effort.
AB  - When humans and other animals make decisions in their natural environments
      prospective rewards have to be weighed against costs. It is well established that
      increasing costs lead to devaluation or discounting of reward. While our
      knowledge about discount functions for time and probability costs is quite
      advanced, little is known about how physical effort discounts reward. In the
      present study we compared three different models in a binary choice task in which
      human participants had to squeeze a handgrip to earn monetary rewards: a linear,
      a hyperbolic, and a parabolic model. On the group as well as the individual
      level, the concave parabolic model explained most variance of the choice data,
      thus contrasting with the typical hyperbolic discounting of reward value by
      delay. Research on effort discounting is not only important to basic science but
      also holds the potential to quantify aberrant motivational states in
      neuropsychiatric disorders. 

PMID- 24140078
TI  - The impact of cefepime as first line therapy for neutropenic fever on Clostridium
      difficile rates among hematology and oncology patients.
AB  - After changing empiric treatment of febrile neutropenia from meropenem to
      cefepime, the effect on Clostridium difficile infection (CDI) was investigated.
      The change was assessed using an autoregressive model. A significant increase in
      CDI rates occurred following the introduction of cefepime. There may be an
      association between increased cefepime usage and CDI. 

PMID- 24140079
TI  - Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre
      eclampsia.
AB  - OBJECTIVE: A common haplotype M2 consisting of minor SNP alleles located in the
      ANXA5 gene promoter region has been described as a risk factor for various
      obstetric complications such as recurrent pregnancy loss, pre-eclampsia and
      pregnancy-related thrombophilic disorder. However, the question of whether it is
      the maternal or fetal genotype that contributes to the onset of these disorders
      remains to be resolved. METHODS: We analyzed ANXA5 gene variants in the blood and
      placental tissues from pre-eclampsia patients and normotensive controls. ANXA5
      expression was examined by qRT-PCR, Western blotting and immunostaining. Results
      were compared between M2 and non-M2 carriers. RESULTS: The M2 haplotype was found
      to be significantly frequent in placentas from pre-eclamptic patients relative to
      the controls (25.5% versus 10%, P = 0.044), In contrast, no significant
      differences were observed in maternal blood (13.0% versus 11.3%, P = 0.597). The
      placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When
      examined by Western blot and immunostaining, the ANXA5 protein levels were found
      to be affected more by the placental than the maternal genotype. Histological
      examination of the placentas from the pre-eclamptic patients demonstrated that a
      placental M2 haplotype correlated more closely than maternal M2 with the severity
      of perivillous fibrin deposition. CONCLUSIONS: Although preliminary, these
      results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter,
      whether transmitted maternally or paternally, might be an essential determinant
      of an increased risk of pre-eclampsia via local thrombophilia at the feto
      maternal interface.

PMID- 24140080
TI  - Evidence of sexual dimorphism in the placental function with severe preeclampsia.
AB  - Preeclampsia (PE) affects 5-8% of pregnancies and is responsible for 18% of
      maternal deaths in the US, and for long-term complications in mother and child.
      PE is an inflammatory state and may influence placental function in a sex
      specific manner. We determined if there is a sexual dimorphism in the placental
      inflammatory and apoptotic responses in preeclamptic pregnancies. Placentas were
      collected from normotensive and preeclamptic pregnancies with either male or
      female fetuses (MPE and FPE respectively) after c-section at term with no labor.
      Expression patterns of markers of inflammation measured by ELISA, as well as
      hypoxia, apoptosis and angiogenesis markers measured by Western blotting were
      determined in the placenta. Consistent with previous studies, an increase in
      inflammation, hypoxia, and apoptotic cell death was observed in PE compared to
      normotensive pregnancies. Levels of TNFalpha, IL-6 and IL-8, and HIF-1alpha were
      significantly greater, whereas the angiogenic marker VEGF was significantly
      reduced in MPE vs. FPE. Sexual dimorphism was also observed in the activation of
      cell death: the number of TUNEL-positive cells, and the expression pro-apoptotic
      markers PUMA and Bax being higher in MPE vs. FPE. We also found an increase in
      the levels of protein and DNA-binding activity of NFkappaB p65 in MPE vs. FPE. In
      summary, we show here that in preeclamptic pregnancies the placentas of males
      were associated with significantly higher expression of inflammatory, hypoxia and
      apoptotic molecules but reduced expression of a pro-angiogenic marker compared to
      placentas of female fetuses. We propose that the transcription factor NFkappaB
      p65 might, at least partially, be involved in sexual dimorphism during PE. 

PMID- 24140082
TI  - CHEK again: revisiting the development of CHK1 inhibitors for cancer therapy.
AB  - CHEK1 encodes the serine/threonine kinase CHK1, a central component of the DNA
      damage response. CHK1 regulates cell cycle checkpoints following genotoxic stress
      to prevent the entry of cells with damaged DNA into mitosis and coordinates
      various aspects of DNA repair. Accordingly, CHK1 has become a target of
      considerable interest in oncology. CHK1 inhibitors potentiate the efficacy of DNA
      damaging chemotherapeutics by abrogating CHK1-mediated cell cycle arrest and
      preventing repair of damaged DNA. In addition, CHK1 inhibitors interfere with the
      biological role of CHK1 as a principal regulator of the cell cycle that controls
      the initiation of DNA replication, stabilizes replication forks, and coordinates
      mitosis. Since these functions of CHK1 facilitate progression through an
      unperturbed cell cycle, CHK1 inhibitors are being developed not only as
      chemopotentiators, but also as single-agent therapies. This review is intended to
      provide information on the current progress of CHK1 inhibitors in pre-clinical
      and clinical development and will focus on mechanisms of single-agent activity
      and potential strategies for patient tailoring and combinations with non
      genotoxic agents. 

PMID- 24140081
TI  - Small and large animal models in cardiac contraction research: advantages and
      disadvantages.
AB  - The mammalian heart is responsible for not only pumping blood throughout the body
      but also adjusting this pumping activity quickly depending upon sudden changes in
      the metabolic demands of the body. For the most part, the human heart is capable
      of performing its duties without complications; however, throughout many decades
      of use, at some point this system encounters problems. Research into the heart's
      activities during healthy states and during adverse impacts that occur in disease
      states is necessary in order to strategize novel treatment options to ultimately
      prolong and improve patients' lives. Animal models are an important aspect of
      cardiac research where a variety of cardiac processes and therapeutic targets can
      be studied. However, there are differences between the heart of a human being and
      an animal and depending on the specific animal, these differences can become more
      pronounced and in certain cases limiting. There is no ideal animal model
      available for cardiac research, the use of each animal model is accompanied with
      its own set of advantages and disadvantages. In this review, we will discuss
      these advantages and disadvantages of commonly used laboratory animals including
      mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research
      is to enhance our understanding of human health and disease and help improve
      clinical outcomes, we will also discuss the role of human cardiac tissue in
      cardiac research. This review will focus on the cardiac ventricular contractile
      and relaxation kinetics of humans and animal models in order to illustrate these
      differences. 

PMID- 24140084
TI  - Survey of the clinical assessment and utility of near-infrared cerebral oximetry
      in cardiac surgery.
AB  - OBJECTIVES: Near-infrared cerebral oximetry increasingly is used for monitoring
      during cardiac surgery. Nonetheless, the scientific basis for incorporating this
      technology into clinical practice, the indications for when to do so, and
      standard diagnostic and treatment algorithms for defining abnormal values are yet
      to be rigorously defined. The authors hypothesized that there would be (1)
      variation in clinical use and practices for near-infrared spectroscopy (NIRS),
      and (2) variation in management of patients when clinicians are provided with
      NIRS information. In order to test this hypothesis, they sought to assess the
      nature and strength of response heterogeneity among anesthesiologists and cardiac
      perfusionists when provided with cardiac surgery patient scenarios and cerebral
      oximetry data. DESIGN: A prospectively collected survey. SETTING: A hospital
      based, multi-institutional, multinational study. PARTICIPANTS: By e-mail, the
      authors surveyed the membership of the Society of Cardiovascular
      Anesthesiologists and the online Cardiovascular Perfusion Forum. INTERVENTIONS:
      This survey was focused on ascertaining what actions clinicians would take in
      each scenario, given case information and cerebral oximetry tracings. Questions
      were based on 11 patient scenarios selected to represent small, large, symmetric,
      or asymmetric decreases in measured regional cerebral oxygen saturation (rScO2)
      encountered during cardiac surgery. Information on the respondents' (n = 796; 73%
      anesthesiologists) clinical practice, demography, and cerebral oximetry
      utilization was collected. An index of dispersion was used to assess response
      heterogeneity overall and within demographic subgroups. MEASUREMENTS AND MAIN
      RESULTS: The majority of respondents indicated that cerebral oximetry monitoring
      was either useful or an essential monitor, especially perfusionists and
      clinicians who used cerebral oximetry most frequently. There were marked
      differences in responses between perfusionists and anesthesiologists for 4 of the
      6 scenarios (p<0.005 for each of these 4 scenarios) occurring during
      cardiopulmonary bypass. Scenarios having greatest rScO2 reduction or asymmetry in
      rScO2 were associated with the highest dispersion, indicating least agreement in
      management. Scenarios with mild or moderate rScO2 reduction were associated with
      the lowest dispersion, indicating greater agreement in management. CONCLUSIONS:
      Although experimental data gradually are accumulating to support the role for
      cerebral oximetry monitoring during cardiac surgery, the results of the present
      survey support the view that its role remains poorly defined, and consensus for
      its appropriate use is lacking. Importantly, the authors observed marked
      variation in the use, perceived utility, and management of patients for 4 of the
      6 CPB scenarios between perfusionists and anesthesiologists who share the
      management of CPB. These findings support the need for well-designed, adequately
      powered clinical trials examining the value of this technology.

PMID- 24140085
TI  - Pro: patient-prosthetic mismatch in aortic valve replacement.

PMID- 24140083
TI  - Targeting tumor-stromal interactions in bone metastasis.
AB  - Bone metastasis is a frequent occurrence in late stage solid tumors, including
      breast cancers, prostate or lung. However, the causes for this proclivity have
      only recently been elucidated. Significant progress has been made in the past
      decade toward understanding the molecular underpinnings of bone metastasis, and
      much of this research reveals a crucial role of the host stroma in each step of
      the metastatic cascade. Tumor-stromal interactions are crucial in engineering a
      pre-metastatic niche, accommodating metastatic seeding, and establishing the
      vicious cycle of bone metastasis. Current treatments in bone metastasis focus on
      latter steps of the metastatic cascade, with most treatments targeting the
      process of bone remodeling; however, emerging research identifies many other
      candidates as promising targets. Host stromal cells including platelets and
      endothelial cells are important in the early steps of metastatic homing,
      attachment and extravasation while a variety of immune cells, parenchymal cells
      and mesenchymal cells of the bone marrow are important in the establishment of
      overt, immune-suppressed metastatic lesions. Many participants during these steps
      have been identified and functionally validated. Significant contributors include
      integrins, (alphavbeta3, alpha2beta1, alpha4beta1), TGFbeta family members, bone
      resident proteins (BSP, OPG, SPARC, OPN), RANKL, and PTHrP. In this review, we
      will discuss the contribution of host stromal cells to pre-metastatic niche
      conditioning, seeding, dormancy, bone-remodeling, immune regulation, and
      chemotherapeutic shielding in bone metastasis. Research exploring these
      interactions between bone metastases and stromal cells has yielded many
      therapeutic targets, and we will discuss both the current and future therapeutic
      avenues in treating bone metastasis. 

PMID- 24140086
TI  - CASE 8--2014 Anesthetic management of bilateral lung transplantation from donor
      lungs managed by the organ care system.

PMID- 24140087
TI  - Screening of currently used pesticides in water, sediments and biota of the
      Guadalquivir River Basin (Spain).
AB  - The occurrence of 50 currently used pesticides and their transformation products
      in surface and waste waters, sediment and fish in the Guadalquivir River Basin
      was determined in 2010 and 2011. After selective sample extraction, pesticides
      were identified and quantified by liquid chromatography coupled to tandem mass
      spectrometry (LC-MS/MS). The contamination profile in water and sediments is
      marked by the presence of organophosphorus and triazines. Transformation products
      were even at higher concentrations than parent pesticides. A wider range of
      pesticides was present in water than in sediments but none of them were detected
      in fish. The mean concentrations ranged from 0.2 to 13.0 ng/L in water and from
      0.1 to 13.2 ng/g d.w. in sediment. The spatial distribution of most pesticides
      was consistent with the agricultural activities of the area or their urban
      applications. The waste water treatment plant effluents that impact the river are
      minor sources for few pesticides but for most of them run-off would be the most
      important contribution. The temporal distribution showed differences between both
      sampling campaigns related to the river flow. The low-flow produced a pesticide
      concentration effect, generating higher levels in water and accumulation in
      sediments. This forecasts a hazard in future scenarios if the current situation
      of the climate change and water scarcity evolves to more critical conditions
      highlighting the need of these monitoring studies.

PMID- 24140088
TI  - Utility of SPECT/CT for periparotid sentinel lymph node mapping in the surgical
      management of head and neck melanoma.
AB  - PURPOSE: Sentinel lymph node (SLN) biopsy is instrumental in staging and
      treatment of cutaneous melanoma. SPECT/CT, single-photon emission computed
      tomography (SPECT) integrated with computed tomography (CT), increases the
      accuracy of SLN mapping to improve surgical planning. SPECT/CT can correct for
      signal scatter to prevent masking, which is especially common in the head and
      neck. For periparotid lymph nodes SPECT/CT may improve localization of SLNs
      compared to lymphoscintigraphy. MATERIALS/METHODS: Hospital charts were reviewed
      for 14 patients with melanoma and suspected lymphatic drainage to the parotid
      region who received lymphoscintigraphy followed by SPECT/CT prior to surgical
      excision and SLN. RESULTS: Overall, SPECT/CT provided data, which changed
      management in 57% of patients. CONCLUSIONS: Fifty-seven percent of our patients
      benefited from use of SPECT/CT. The distinction between level II and parotid
      sentinel lymph nodes was clearly identified through SPECT/CT images. We believe
      that patients with melanoma draining to the parotid region would benefit from
      SPECT/CT SLN mapping.

PMID- 24140089
TI  - Exercise and bone: where do we stand?

PMID- 24140090
TI  - Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4
      induced insulin secretion in INS-1 cells.
AB  - OBJECTIVE: Exendin-4 (Ex-4) is an anti-diabetic drug that is a potent agonist of
      the glucagon-like peptide-1 (GLP-1) receptor. It has already been approved for
      the treatment of type 2 diabetes mellitus, but its underlying mechanisms of
      action are not fully understood. Calcium/calmodulin-dependent serine protein
      kinase (CASK), which plays a vital role in the transport and release of
      neurotransmitters in neurons, is expressed in pancreatic islet cells and beta
      cells. This study aimed to investigate whether CASK is involved in the insulin
      secretagogue action induced by Ex-4 in INS-1 cells. MATERIAL/METHODS: A glucose
      stimulated insulin secretion (GSIS) assay was performed with or without siRNA
      treatment against CASK. The expression level and location of CASK were evaluated
      by real-time PCR, western blotting and immunofluorescence. With the use of a
      protein kinase A (PKA) inhibitor or an exchange protein directly activated by
      cAMP-2 (Epac2) agonist, immunoblotting was performed to establish the signaling
      pathway through which Ex-4 alters CASK expression. RESULTS: Knock-down of CASK
      significantly attenuated the Ex-4-enhanced insulin release, and we showed that Ex
      4 could increase transcription of CASK mRNA and expression of CASK protein but
      did not change the cellular location of CASK. A PKA inhibitor reduced the ability
      of Ex-4 to stimulate CASK expression, but an Epac2 agonist had no effect
      suggesting that regulation was mediated by the cAMP/PKA pathway. CONCLUSION: Our
      study suggests that the stimulation of beta-cell insulin secretion by Ex-4 is
      mediated, at least in part, by CASK via a novel signaling mechanism.

PMID- 24140091
TI  - Irisin in patients with nonalcoholic fatty liver disease.
AB  - OBJECTIVE: Irisin is a recently discovered myokine proposed to increase
      thermogenesis-related energy expenditure and improve metabolism. We aimed to
      comparatively evaluate serum irisin levels in patients with biopsy-proven
      nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association
      with disease severity. METHODS: Fifteen and 16 consecutively enrolled patients
      with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis
      (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were
      recruited. Irisin, established adipokines and biochemical tests were measured.
      RESULTS: Serum irisin levels were statistically different in obese controls
      (33.7+/-2.7 ng/mL; p<0.001) and patients with NAFL (30.5+/-1.5 ng/mL; p<0.001)
      and NASH (35.8+/-1.9 ng/mL; p=0.001) compared with lean controls (47.7+/-2.0
      ng/mL), but were similar among patients with NAFL, NASH and obese controls. This
      difference remained significant after adjustment for body mass index (or waist
      circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI),
      exercise and time since blood collection. Serum leptin and adiponectin, but not
      irisin, levels were independently from BMI correlated with insulin resistance and
      cardiometabolic factors. Serum irisin tended to be higher in patients with
      (36.7+/-2.4 ng/mL) than without (30.8+/-1.2 ng/mL; p=0.02) portal inflammation
      and independently associated with the latter; these data need to be confirmed by
      future studies. CONCLUSIONS: Serum irisin levels differ between lean controls and
      obese controls or NAFLD patients. Despite similar circulating irisin levels
      between NAFL and NASH groups, irisin may be independently and positively
      associated with the presence of portal inflammation. Future clinical and
      mechanistic studies are needed to confirm and extend these data.

PMID- 24140092
TI  - Contribution of very low-density lipoprotein triglyceride fatty acids to
      postabsorptive free fatty acid flux in obese humans.
AB  - OBJECTIVE: In the fasting state, plasma free fatty acids (FFA) are thought to
      derive almost exclusively from adipose tissue lipolysis. However, there are mixed
      reports as to whether the spillover of fatty acids (FA) from very low-density
      lipoprotein triglyceride (VLDL-TG) hydrolysis contributes significantly to the
      plasma FFA pool. Because substantial VLDL-TG fatty acid spillover into the plasma
      FFA pool would profoundly impact the interpretation of isotope dilution measures
      of FFA flux, we investigated the contribution of VLDL-TG spillover to plasma FFA
      appearance. MATERIALS/METHODS: Eighteen obese adults (15 women) participated in
      these studies. Each volunteer received a primed, continuous infusion of their own
      ex-vivo labeled ([1-(14)C]triolein) VLDL-TG and a continuous infusion of [U
      (13)C]oleate (8 nmol . kg fat free mass(-1) . min(-1)) to measure VLDL-TG and FFA
      rate of appearance (Ra), respectively. The presence of (14)C-oleate in the plasma
      FFA-oleate pool was used to calculate the contribution of spillover from VLDL-TG
      oleate to the plasma FFA-oleate Ra. RESULTS: The spillover rate of VLDL-TG-oleate
      into plasma FFA-oleate was 6 +/- 2 MUmol/min (7% +/- 2% of [(14)C]oleate from
      VLDL-TG) and FFA-oleate flux was 240 +/- 61 MUmol/min. Thus, only 3% +/- 1% of
      total plasma FFA-oleate appearance could be accounted for by VLDL-TG spillover.
      CONCLUSION: The contribution of VLDL-TG spillover to the total plasma FFA pool is
      negligible and will not materially affect the interpretation of FFA flux measures
      as an index of adipose tissue lipolysis.

PMID- 24140093
TI  - Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of
      excess body weight on insulin resistance and risk for myelodysplastic syndrome.
AB  - OBJECTIVE: Excess body weight has been implicated in the pathogenesis of
      myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A
      reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has
      been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting
      visceral fat mass, all potential mediators of the effects of obesity on insulin
      resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital
      based case-control study, we studied 101 cases with incident, histologically
      confirmed primary MDS and 101 controls matched on gender, age and date of
      diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin
      receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin
      A, lower adiponectin and lower free leptin were all individually and
      independently associated with higher risk of MDS before and after controlling for
      matching and risk factors, such as age, gender, date of diagnosis, body mass
      index (BMI), family history of lymphohematopoietic cancer, smoking history and
      serum insulin. Interestingly, we have shown that these associations were
      prominent among overweight/obese individuals and persisted after controlling for
      BMI and serum insulin indicating that their effects are above and beyond
      insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and
      free leptin are associated with higher risk of MDS particularly among
      overweight/obese individuals. These findings suggest that the association between
      excessive weight gain and the risk of MDS could be mediated by fetuin-A,
      adiponectin and free leptin, which may have potential clinical and preventive
      implications.

PMID- 24140094
TI  - Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells.
AB  - Glucagon-like peptide-1 (GLP-1), an incretin hormone, is released from intestinal
      L-cells in response to nutrients. GLP-1 lowers blood glucose levels by
      stimulating insulin secretion from pancreatic beta-cells in a glucose-dependent
      manner. In addition, GLP-1 slows gastric emptying, suppresses appetite, reduces
      plasma glucagon, and stimulates glucose disposal, which are beneficial for
      glucose homeostasis. Therefore, incretin-based therapies such as GLP-1 receptor
      agonists and inhibitors of dipeptidyl peptidase IV, an enzyme which inactivates
      GLP-1, have been developed for treatment of diabetes. This review outlines our
      knowledge of the actions of GLP-1 on insulin secretion and biosynthesis, beta
      cell proliferation and regeneration, and protection against beta-cell damage, as
      well as the involvement of recently discovered signaling pathways of GLP-1
      action, mainly focusing on pancreatic beta-cells. 

PMID- 24140095
TI  - Effects of a nonnutritive sweetener on body adiposity and energy metabolism in
      mice with diet-induced obesity.
AB  - OBJECTIVE: Nonnutritive sweeteners (NNSs) have been studied in terms of their
      potential roles in type 2 diabetes, obesity, and related metabolic disorders.
      Several studies have suggested that NNSs have several specific effects on
      metabolism such as reduced postprandial hyperglycemia and insulin resistance.
      However, the detailed effects of NNSs on body adiposity and energy metabolism
      have not been fully elucidated. We investigated the effects of an NNS on energy
      metabolism in mice with diet-induced obesity (DIO). METHODS: DIO mice were
      divided into NNS-administered (4% NNS in drinking water), sucrose-administered
      (33% sucrose in drinking water), and control (normal water) groups. After
      supplementation for 4 weeks, metabolic parameters, including uncoupling protein
      (UCP) levels and energy expenditure, were assessed. RESULTS: Sucrose
      supplementation increased hyperglycemia, body adiposity, and body weight compared
      to the NNS-administered and control groups (P<0.05 for each). In addition, NNS
      supplementation decreased hyperglycemia compared to the sucrose-administered
      group (P<0.05). Interestingly, NNS supplementation increased body adiposity,
      which was accompanied by hyperinsulinemia, compared to controls (P<0.05 for
      each). NNS also increased leptin levels in white adipose tissue and triglyceride
      levels in tissues compared to controls (P<0.05 for each). Notably, compared to
      controls, NNS supplementation decreased the UCP1 level in brown adipose tissue
      and decreased O2 consumption in the dark phase. CONCLUSIONS: NNSs may be good
      sugar substitutes for people with hyperglycemia, but appear to influence energy
      metabolism in DIO mice.

PMID- 24140096
TI  - beta-Hydroxy-beta-methylbutyrate (HMB) and prevention of muscle wasting.

PMID- 24140097
TI  - Cross-talk between the heart and adipose tissue in cachectic heart failure
      patients with respect to alterations in body composition: a prospective study.
AB  - OBJECTIVES: Cardiac cachexia (CC) is associated with changes in body composition.
      Lipolysis and increased energy expenditure caused by A- and B natriuretic
      peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis
      that neurohormones and adipokines are associated with body composition in CC and
      that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place.
      METHODS: Body composition with regard to FFM, FM, and body fat distribution was
      assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients
      with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and
      individuals with prior myocardial infarction-both n = 19) who were followed for
      12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial
      dysfunction were measured. RESULTS: N-terminal proBNP (NT-proBNP), midregional
      proANP (MR-proANP), and total adiponectin were elevated in CHF (p<0.001) and
      correlated inversely to BMI and FM. An inverse correlation was observed between
      pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was
      unaltered in all groups even though FM increased by 1.35 kg (p<0.05) and FFM
      decreased by 0.5 kg (p<0.05) in CC patients. The latter correlated inversely to
      baseline NT-proBNP, MR-proANP, and MR-proADM (p<0.05). No correlation to changes
      in FM was found. CONCLUSIONS: FM was associated with plasma NPs and total
      adiponectin at baseline; whereas changes in FM and FFM did not correlate to
      changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but
      FM increased, despite stable body weight in CC.

PMID- 24140098
TI  - A review of the literature on common CYP17A1 mutations in adults with 17
      hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans
      and functional characteristics of a novel mutation.
AB  - OBJECTIVE: 17alpha-hydroxylase/17,20-lyase deficiency is a rare form of
      congenital adrenal hyperplasia, characterized by hypertension and sexual
      infantilism and caused by loss-of-function mutations in CYP17A1. This study
      investigated the clinical and molecular characteristics of six adults with
      17alpha-hydroxylase/17,20-lyase deficiency and the functional consequences of a
      novel CYP17A1 mutation. MATERIALS AND METHODS: Six phenotypic females, three with
      46,XY and three with 46,XX karyotypes, presented with primary amenorrhea and
      hypertension. All had elevated levels of plasma adrenocorticotropic hormone,
      serum gonadotropin, progesterone, and 11-deoxycorticosterone, and reduced
      testosterone and dehydroepiandrosterone sulfate (DHEA-S). All coding exons and
      flanking intronic sequences of CYP17A1 were directly sequenced using genomic DNA.
      Wild-type and mutant CYP17A1 cDNAs were inserted into the pcDNA3.1/V5-His-P450c17
      vector, and transiently expressed in COS-7 cells. This was followed by an
      assessment of 17alpha-hydroxylase and 17,20-lyase activities by measuring the
      conversions of progesterone to 17-hydroxyprogesterone and 17-hydroxypregnenolone
      to DHEA. RESULTS: The mutation analysis identified one patient with compound
      heterozygosity for p.H373L and p.W406L, one with compound heterozygosity for
      p.H373L and p.A174E, three with compound heterozygosity for p.Y329fs and p.H373L,
      and one with homozygosity for p.H373L. An in vitro functional analysis of the
      novel p.W406L mutation revealed a complete loss of 17alpha-hydroxylase/17, 20
      lyase activities. CONCLUSIONS: p.H373L was the most common mutation among these
      Korean patients, consistent with the high allele frequency of p.H373L in Chinese
      and Japanese populations, suggesting possible founder effects in Asian countries.
      The novel p.W406L mutation caused a complete loss of both catalytic activities,
      indicating that this amino acid is critical for P450c17 function.

PMID- 24140099
TI  - Higher serum bilirubin level as a protective factor for the development of
      diabetes in healthy Korean men: a 4 year retrospective longitudinal study.
AB  - OBJECTIVE: Bilirubin, a natural product of heme catabolism by heme oxygenase, one
      of key antioxidant enzymes, has been recognized as a substance with potent
      antioxidant and cytoprotective properties. Several studies have shown a
      significant negative relationship between serum bilirubin levels and the risk of
      metabolic disorders, including type 2 diabetes. However, longitudinal studies
      investigating the association of elevated serum bilirubin levels and type 2
      diabetes are lacking. In the present study, we aimed to investigate the
      longitudinal effects of baseline serum bilirubin concentrations on the
      development of type 2 diabetes in healthy Korean men. MATERIALS AND METHODS: This
      4 year retrospective longitudinal observational study was conducted at the Asan
      Medical Center, Seoul, Republic of Korea. The study population consisted of 5960
      men without type 2 diabetes who underwent routine health examinations in 2007
      (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were
      determined by the vanadate oxidation method. RESULTS: During a 4 year period, 409
      incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes
      decreased across the baseline bilirubin quartile categories (P for trend <0.001).
      In multivariable-adjusted model, the relative risk (RR) for the development of
      type 2 diabetes was significantly lower in the highest (i.e., 1.30-2.00 mg/dl)
      than in the lowest bilirubin quartile category (i.e., <= 0.90 mg/dl), even after
      adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48-0.99,
      P for trend = 0.041). CONCLUSIONS: The results indicate that serum total
      bilirubin level may provide additional information for predicting future
      development of type 2 diabetes in healthy subjects.

PMID- 24140100
TI  - The heart is better protected against myocardial infarction in the fed state
      compared to the fasted state.
AB  - OBJECTIVE: A variety of calorie restriction diets and fasting regimens are
      popular among overweight people. However, starvation could result in unexpected
      cardiovascular effects. Therefore, it is necessary to evaluate the short-term
      effects of diets on cardiovascular function, energy metabolism and potential risk
      of heart damage in case of myocardial infarction. The objective of the present
      study was to investigate whether the increased level of glucose oxidation or
      reduction of fatty acid (FA) load in the fed state provides the basis for
      protection against myocardial infarction in an experimental rat model of ischemia
      reperfusion. MATERIALS/METHODS: We tested the effects of the availability of
      energy substrates and their metabolites on the heart functionality and energy
      metabolism under normoxic and ischemia-reperfusion conditions. RESULTS: In a
      fasted state, the heart draws energy exclusively from FAs, whereas in a fed
      state, higher concentration of circulating insulin ensures a partial switch to
      glucose oxidation, while the load of FA on heart and mitochondria is reduced.
      Herein, we demonstrate that ischemic damage in hearts isolated from Wistar rats
      and diabetic Goto-Kakizaki rats is significantly lower in the fed state compared
      to the fasted state. CONCLUSIONS: Present findings indicate that postprandial or
      fed-state physiology, which is characterised by insulin-activated glucose and
      lactate utilisation, is protective against myocardial infarction. Energy
      metabolism pattern in the heart is determined by insulin signalling and the
      availability of FAs. Overall, our study suggests that even overnight fasting
      could provoke and aggravate cardiovascular events and high-risk cardiovascular
      patients should avoid prolonged fasting periods.

PMID- 24140101
TI  - Estrogen receptor alpha is not a candidate gene for metabolic syndrome in
      Caucasian elderly subjects.
AB  - OBJECTIVE: Variants of estrogen receptor alpha (ERalpha) have been associated
      with obesity, dyslipidemia, diabetes and blood pressure. The Middle East
      registers some of the highest rate of metabolic syndrome worldwide. The aim of
      this study is to investigate the relationship between metabolic syndrome, a
      clustered combination of these metabolic factors, and polymorphisms PvuII and
      XbaI of ERalpha in Lebanese Caucasian elderly overweight subjects.
      MATERIAL/METHODS: 250 Caucasian Lebanese unrelated elderly men and women, median
      age 71 years, were studied. ERalpha intronic polymorphisms variants, PvuII and
      XbaI diplotypes and genotypes, were examined. Associations with metabolic
      syndrome, defined by the American Heart Association/National Heart, Lung, and
      Blood Institute (AHA/NHLBI), and its components, namely high density lipoprotein
      (HDL), fasting glucose levels, blood pressure, and waist circumference were
      evaluated in regression models. RESULTS: ER alpha diplotypes and genotypes
      distributions were similar between participants with and without metabolic
      syndrome, in the overall group of subjects, and by gender. No consistent
      associations between the diplotypes and genotypes tested and metabolic syndrome,
      or its components, could be detected. CONCLUSIONS: Genetic variants in ERalpha
      were not associated with metabolic syndrome or its components, in a group of 250
      Lebanese Caucasian elderly participants, a group with a high prevalence of
      metabolic syndrome.

PMID- 24140102
TI  - New methodology for facial nerve monitoring in extracranial surgeries of vascular
      malformations.
AB  - OBJECTIVE: To develop a more reliable methodology for monitoring the facial nerve
      in surgeries of vascular malformations where the extracranial segment of the
      nerve is at risk. METHODS: Our methodology comprises: (1) preoperative mapping to
      identify the anatomical location of the nerve branches, (2) continuous
      intraoperative monitoring of the compound muscle action potential (CMAP) by
      stimulating the facial nerve extracranially, in close proximity to where the
      trunk of the facial nerve exits the skull at the stylomastoid foramen, (3)
      intraoperative mapping to identify the nerve branches during surgical dissection
      and quantify the innervating contribution of each branch to the target muscle.
      RESULTS: Only three out of 201 surgeries (1.5%) had complete facial nerve trunk
      injury as a consequence of facial vascular malformation surgery. CONCLUSIONS: We
      developed a new method to continuously stimulate the facial nerve extracranially
      eliciting an objective parameter--the CMAP amplitude--to constantly measure
      changes in the muscle responses throughout surgery, alerting the surgeon before
      the facial nerve is severely injured. Our methodology notably reduces the
      complete facial nerve injury during extracranial surgery of facial vascular
      malformations. SIGNIFICANCE: This comprehensive methodology may also be a
      valuable tool to prevent facial nerve injury during other types of extracranial
      surgeries where radical excisions are required.

PMID- 24140103
TI  - Residual alterations of brain electrical activity in clinically asymptomatic
      concussed individuals: an EEG study.
AB  - OBJECTIVE: To examine the neural substrates underlying performance on Immediate
      Post-Concussion Assessment and Cognitive Testing (ImPACT) and HeadRehab Virtual
      Reality (VR) balance and spatial modules in a concussed and control group.
      METHODS: Thirteen controls and seven concussed participants were fitted with a
      Geodesic 128-channel EEG cap and completed three assessments: EEG baseline,
      ImPACT testing, and VR balance and spatial modules. Concussed participants
      completed were tested within 8 (5 +/- 1) days after injury. RESULTS: EEG power
      was significantly (p < .05) decreased in the concussed group over all testing
      modalities. EEG coherence was significantly (p < .05) increased in the concussed
      group during EEG baseline and ImPACT. For VR testing, two conditions showed
      significant (p < .05) increases in EEG coherence between ROIs, while two
      different conditions showed significant (p < .05) decreases in coherence levels.
      CONCLUSIONS: Concussed participants passed all clinical concussion testing tools,
      but showed pathophysiological dysfunction when evaluating EEG variables.
      SIGNIFICANCE: Concussed participants are able to compensate and achieve normal
      functioning due to recruiting additional brain networks. This allows concussed
      participants to pass clinical tests while still displaying electrophysiological
      deficits and clinicians must consider this information when making return-to-play
      decisions.

PMID- 24140104
TI  - Comparison of the large-scale periplasmic proteomes of the Escherichia coli K-12
      and B strains.
AB  - Escherichia coli typically secretes many proteins into the periplasmic space, and
      the periplasmic proteins have been used for the secretory production of various
      proteins by the biotechnology industry. However, the identity of all of the E.
      coli periplasmic proteins remains unknown. Here, high-resolution periplasmic
      proteome reference maps of the E. coli K-12 and B strains were constructed and
      compared. Of the 145 proteins identified by tandem mass spectrometry, 61 proteins
      were conserved in the two strains, whereas 11 and 12 strain-specific proteins
      were identified for the E. coli K-12 and B strains, respectively. In addition, 27
      proteins exhibited differences in intensities greater than 2-fold between the K
      12 and B strains. The periplasmic proteins MalE and OppA were the most abundant
      proteins in the two E. coli strains. Distinctive differences between the two
      strains included several proteins that were caused by genetic variations, such as
      CybC, FliC, FliY, KpsD, MglB, ModA, and Ybl119, hydrolytic enzymes, particularly
      phosphatases, glycosylases, and proteases, and many uncharacterized proteins.
      Compared to previous studies, the localization of many proteins, including 30
      proteins for the K-12 strain and 53 proteins for the B strain, was newly
      identified as periplasmic. This study identifies the largest number of proteins
      in the E. coli periplasm as well as the dynamics of these proteins. Additionally,
      these findings are summarized as reference proteome maps that will be useful for
      studying protein secretion and may provide new strategies for the enhanced
      secretory production of recombinant proteins.

PMID- 24140105
TI  - Aerobic utilization of crude glycerol by recombinant Escherichia coli for
      simultaneous production of poly 3-hydroxybutyrate and bioethanol.
AB  - Crude glycerol, an inevitable byproduct during biodiesel production, is emerging
      as a potential feedstock for fermentation, due to its availability and a
      reasonable price. Biological utilization of abundant crude glycerol to several
      value added products is contemporary research area with beneficial features.
      Solving the problem of proper disposal and raising economic viability of
      biodiesel industries. Several researches have been directed toward the production
      of numerous products by using Escherichia coli, an ideal organism for
      heterologous expression of various foreign proteins. In this fashion, recombinant
      E. coli strains were constructed for the simultaneous production of poly 3
      hydroxybutyrate (P3HB) and bioethanol from crude glycerol. The incorporation of
      aldehyde reductase (Alrd) and aldehyde dehydrogenase (AldH) in recombinant strain
      showed 2-fold increment in crude glycerol utilization under aerobic condition.
      Moreover, these two enzymes introduced an alternative pathway leading toward the
      potential production of bioethanol which was more than redox-balancing steps.
      Acetate was accumulated as an intermediate product. Subsequently, acetate was
      utilized as substrate in the second pathway, which directly converted acetyl-CoA
      to P3HB. This strategy demonstrated a potential production manner of bioethanol
      as an extracellular product and P3HB as water insoluble inclusion bodies inside
      E. coli. The maximum production of bioethanol and P3HB in the recombinant strain
      was 0.8 g L(-1) (17.4 mmol L(-1)) and 30.2% (w/w dry cell weight), respectively,
      which were higher than the parental strain.

PMID- 24140106
TI  - Purification and biochemical characterization of a detergent-stable keratinase
      from a newly thermophilic actinomycete Actinomadura keratinilytica strain Cpt29
      isolated from poultry compost.
AB  - An extracellular thermostable keratinase (KERAK-29) was purified and
      biochemically characterized from a thermophilic actinomycete Actinomadura
      keratinilytica strain Cpt29 newly isolated from Algerian poultry compost. The
      isolate exhibited high keratinase production when grown in chicken feather meal
      media (24,000 U/ml). Based on matrix assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF/MS) analysis, the purified enzyme is a
      monomer with a molecular mass of 29,233.10-Da. The data revealed that the 25 N
      terminal residue sequence displayed by KERAK-29 was TQADPPSWGLNNIDRQTAFTKATSI,
      which showed high homology with those of Streptomyces proteases. This keratinase
      was completely inhibited by phenylmethanesulfonyl fluoride (PMSF) and
      diiodopropyl fluorophosphates (DFP), which suggests that it belongs to the serine
      protease family. Using keratin azure as a substrate, the optimum pH and
      temperature values for keratinase activity were pH 10 and 70 degrees C,
      respectively. KERAK-29 was stable between 20 and 60 degrees C and pH 3 and 10 for
      5 and 120 h, respectively, and its thermoactivity and thermostability were
      enhanced in the presence of 5 mM Mn(2+). Its catalytic efficiency was higher than
      that of the KERAB keratinase from Streptomyces sp. strain AB1. KERAK-29 was also
      noted to show high keratinolytic activity and significant stability in the
      presence of detergents, which made it able to accomplish the entire feather
      biodegradation process on its own. The ability of the A. keratinilytica strain
      Cpt29 to grow and produce substantial levels of keratinase using feather as a
      substrate could open new promising opportunities for the valorization of keratin
      containing wastes and reduction of its impacts on the environment.

PMID- 24140107
TI  - Recombinant human LCAT normalizes plasma lipoprotein profile in LCAT deficiency.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for
      cholesterol esterification in plasma. Mutations in the LCAT gene leads to two
      rare disorders, familial LCAT deficiency and fish-eye disease, both characterized
      by severe hypoalphalipoproteinemia associated with several lipoprotein
      abnormalities. No specific treatment is presently available for genetic LCAT
      deficiency. In the present study, recombinant human LCAT was expressed and tested
      for its ability to correct the lipoprotein profile in LCAT deficient plasma. The
      results show that rhLCAT efficiently reduces the amount of unesterified
      cholesterol (-30%) and promotes the production of plasma cholesteryl esters
      (+210%) in LCAT deficient plasma. rhLCAT induces a marked increase in HDL-C
      levels (+89%) and induces the maturation of small prebeta-HDL into alpha
      migrating particles. Moreover, the abnormal phospholipid-rich particles migrating
      in the LDL region were converted in normally sized LDL. 

PMID- 24140108
TI  - Validating the diagnosis of acute ischemic stroke in a National Health Insurance
      claims database.
AB  - BACKGROUND/PURPOSE: The National Health Insurance Research Database, which uses
      claims data from hospitals contracted with the National Health Insurance (NHI)
      program in Taiwan, has been widely used for stroke research. The diagnostic
      accuracy of the NHI claims data with regard to acute ischemic stroke (AIS) has
      rarely been validated. The aim of this study was to validate the diagnosis of AIS
      in NHI claims data using the Taiwan Stroke Registry (TSR) as a reference.
      METHODS: We retrieved patients' data with a discharge diagnosis of AIS [five
      digit International Classification of Diseases Code, 9(th) version (ICD-9 code):
      433xx or 434xx] in a single medical center from August 2006 to December 2008. We
      then linked these patients to the TSR to validate their AIS diagnosis in the
      claims data. The positive predictive value (PPV) and sensitivity were determined.
      RESULTS: We reviewed the claims data of 1736 consecutive AIS patients, of whom
      1299 (74.8%) were linked successfully to the stroke registry database. After
      reviewing the medical records and imaging results of other patients not linked to
      the registry database (n = 437), 235 patients were found to have had an AIS. The
      PPV was 88.4% [95% confidence interval (CI): 86.8-89.8%] and sensitivity was
      97.3% (95% CI: 96.4-98.1%). Forty-four (21.8%) of the false-positive cases (n =
      202) were coded as 433x0 or 434x0. CONCLUSION: The PPV of a diagnosis of AIS in
      the NHI claims data was high. Using five-digit ICD-9 codes to identify AIS cases
      will markedly decrease the false-positive rate compared with using the commonly
      used three-digit method.

PMID- 24140109
TI  - Impact of the apolipoprotein E polymorphism, age and sex on neurogenesis in mice:
      pathophysiological relevance for Alzheimer's disease?
AB  - Apolipoprotein E (ApoE) is found in three different forms in humans (ApoE2, ApoE3
      and ApoE4), and ApoE polymorphism is recognized as a major risk factor for
      Alzheimer's disease (AD). ApoE is involved in lipid and cholesterol transport,
      cell repair, and amyloid-beta deposition and certain studies suggest potential
      implications in neurogenesis. In this regard, we investigated the possible impact
      of the three different human ApoE isoforms on neurogenesis. We used ApoE knock-in
      mice of different ages and sex, and quantified newborn cells in the hippocampus
      by flow cytometry. Young adult ApoE4 mice (10-12 week-old) from both sexes
      displayed reduced neurogenesis compared with wild-types and the other genotypes.
      In addition, young adult ApoE2 female mice showed improved hippocampal progenitor
      cell proliferation. In older mice (1 year), hippocampal neurogenesis was globally
      decreased, particularly in females, and the difference between ApoE4 and the
      other genotypes observed in young animals disappeared for the two sexes, except
      for aged ApoE3 females. Indeed, a surprising protective effect of the ApoE3
      genotype was observed in aged females. Our study highlights the role of ApoE in
      neurogenesis, and shows for the first time an early inequality between the ApoE
      genotypes. The reduced neurogenesis observed for the ApoE4 genotype and the
      improved results obtained in young ApoE2 females support the idea of a difference
      in the balance between neuronal birth and death modulated by the ApoE
      polymorphism in young animals. The maintenance of this balance and its modulation
      can influence pathophysiological mechanisms predisposing to neurodegenerative
      diseases like AD. 

PMID- 24140110
TI  - Different expression of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin in
      ischemic and hemorrhagic stroke: Potential biomarkers in diagnosis.
AB  - The two primary categories of stroke, ischemic and hemorrhagic, both have
      fundamentally different mechanisms and thus different treatment options. These
      two stroke categories were applied to rat models to identify potential biomarkers
      that can distinguish between them. Ischemic stroke was induced by middle cerebral
      artery occlusion (MCAO) without reperfusion while hemorrhagic stroke was induced
      by injecting collagenase IV into the striatum. Brain hemispheres and biofluids
      were collected at two time points: 3 and 6h after stroke. Known molecules were
      tested on the rat samples via quantitative immunoblotting (injured brain, CSF)
      and Banyan's proprietary ELISA assays (CSF, serum). The injured brain
      quantitative analyses revealed that alphaII-spectrin breakdown products (SBDP150,
      SBDP145) were strongly increased after 6h ischemia. In CSF, SBDP145 and ubiquitin
      C-terminal hydrolase-L1 (UCH-L1) levels were elevated after 6h ischemic stroke
      detected by Western blot and ELISA. In serum UCH-L1 levels were increased after 3
      and 6h of ischemia detected by ELISA. However, levels of those proteins in
      hemorrhagic stroke remain normal. In summary, in both the brain and the
      biofluids, SBDPs and UCH-L1 were elevated after ischemic but not hemorrhagic
      stroke. These molecules behaved differently in the two stroke models and thus may
      be capable of being differentiated. 

PMID- 24140111
TI  - Incidence and outcomes of bepridil-induced interstitial pneumonia.
AB  - BACKGROUND: The incidence of bepridil-induced pulmonary toxicity, such as
      interstitial pneumonia, is still unknown. The aim of the present study was to
      evaluate the incidence of bepridil-induced pulmonary toxicity. METHODS AND
      RESULTS: A total of 253 patients treated with bepridil between January 2009 and
      January 2011 were retrospectively evaluated. Eight out of the 222 evaluable
      patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years,
      median age: 81.0 years) showed bepridil-induced pulmonary toxicity. CONCLUSIONS:
      The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study
      population.

PMID- 24140112
TI  - SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3
      copy-number variant.
AB  - Copy-number variants (CNVs) represent a significant interpretative challenge,
      given that each CNV typically affects the dosage of multiple genes. Here we
      report on five individuals with coloboma, microcephaly, developmental delay,
      short stature, and craniofacial, cardiac, and renal defects who harbor
      overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted
      78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo
      dissection of the CNV showed discrete contributions of the planar cell polarity
      effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the
      combinatorial suppression of both genes exacerbated some, but not all, phenotypic
      components. Consistent with these findings, we identified an individual with
      microcephaly, short stature, intellectual disability, and heart defects with a de
      novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional
      testing of this allele in vivo and in vitro showed that the mutation perturbs the
      relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency
      of downstream PUF60 targets. These data inform the functions of two genes not
      associated previously with human genetic disease and demonstrate how CNVs can
      exhibit complex genetic architecture, with the phenotype being the amalgam of
      both discrete dosage dysfunction of single transcripts and also of binary genetic
      interactions. 

PMID- 24140113
TI  - Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes
      in humans.
AB  - Intraflagellar transport (IFT) depends on two evolutionarily conserved modules,
      subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance.
      All six IFT-A components and their motor protein, DYNC2H1, have been linked to
      human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also
      known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome
      (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of
      IFT80, have unknown roles in human disease. To identify additional IFT-B
      components defective in ciliopathies, we independently performed different
      mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in
      1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome
      resequencing in 63 individuals with ATD. We thereby detected biallelic mutations
      in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals
      displayed abnormalities of the thorax and/or long bones, as well as renal,
      hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS.
      Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome
      was present in 2 out of 12 families. Fibroblasts from affected individuals showed
      disturbed ciliary composition, suggesting alteration of ciliary transport and
      signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and
      demonstrated a genetic interaction between ift172 and ift80. In summary, we have
      identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings
      link the group of skeletal ciliopathies to an additional IFT-B component, IFT172,
      similar to what has been shown for IFT-A. 

PMID- 24140115
TI  - Management and outcomes of blunt common and external iliac arterial injuries.
AB  - OBJECTIVE: Blunt iliac arterial injuries (BIAI) require complex management but
      are rare and poorly studied. We investigated the presentation, management, and
      outcomes of patients with blunt common or external iliac arterial injuries.
      METHODS: We identified and reviewed 112 patients with BIAI admitted between 2000
      and 2011 at a Level I trauma center. Patients with common/external iliac artery
      injuries (CE group) were primarily analyzed, with patients with injuries of the
      internal iliac artery or its major branches (IB group) included for comparison of
      pelvic arterial trauma. RESULTS: Twenty-four patients had CE and 88 had IB
      injuries. Mean ages (45 +/- 19 years) and gender (86% male) were similar between
      groups. The mean injury severity score was 40 +/- 14 (CE, 36 +/- 15; IB, 40 +/-
      14; P = .19), indicating severe trauma. Twenty (83%) of the CE patients presented
      with signs of leg malperfusion. Admission factors associated with CE injury were
      crush mechanism of injury (37% vs 17%; P = .03) and pelvic soft tissue trauma
      (50% vs 15%; P < .01). The CE group had higher early mortality rates, both within
      3 hours of admission (50% vs 19%; P = .04) and prior to iliac intervention (42%
      vs 3%; P < .01). Among those surviving to management, CE patients were more
      likely to undergo open repair or revascularization (68% vs 3%; P < .01) and had a
      higher rate of leg amputation (50% vs 6%; P < .01), with 8/12 (67%) culminating
      in hemipelvectomy. Risk factors for amputation included leg malperfusion, high
      grade pelvic fractures, pelvic soft tissue trauma, and increasing leg injury
      severity. Overall mortality was 40%, and was similar between the injury groups.
      Among CE patients, need for amputation, pelvic fractures, and wounds were
      associated with inpatient mortality. CONCLUSIONS: This is the largest series to
      date of blunt CE injuries and demonstrates distinct clinical features and
      outcomes for these patients. They have high risk for early death and proximal leg
      amputation. CE injury is specifically associated with serious open pelvic soft
      tissue injury, which, along with high-grade pelvic fractures, is a risk factor
      for amputation and death. On-demand emergent endovascular intervention may play
      an important role in improving management of these complex injuries.

PMID- 24140116
TI  - Assessment of the quality of glaucoma referral letters based on a survey of
      glaucoma specialists and a glaucoma guideline.
AB  - OBJECTIVE: To assess the quality of glaucoma referral letters and to report on
      the results of a survey of glaucoma specialists about referral letter content.
      DESIGN: Cross-sectional study. PARTICIPANTS: A survey of 135 glaucoma specialists
      and audit of 200 consecutive referral letters to a tertiary glaucoma unit.
      METHODS: An online questionnaire was sent to members of the Canadian and American
      Glaucoma Societies asking what they considered the most important data to be
      included in a glaucoma referral. Consecutive referral letters to a tertiary
      glaucoma unit were assessed for legibility and content on the basis of the survey
      results and information items in current guidelines. MAIN OUTCOME MEASURES:
      Survey outcome and proportion of included content items in referral letters.
      RESULTS: The survey revealed that the top 5 most important data that glaucoma
      specialists would like to be included in a referral letter for progressive
      glaucoma were serial visual fields (VFs), current glaucoma therapy, current
      intraocular pressure (IOP), maximum IOP, and serial disc imaging. These items
      often were omitted in the referral letters audited. A total of 200 referral
      letters were assessed, 46% from ophthalmologists, 42% from optometrists, 10% from
      family practitioners, and 2% from other sources. Reasons for referral were
      diagnosis of glaucoma (37%), unstable glaucoma (25%), angle assessment (17%), and
      others (21%). Some 26% of the referral letters were deemed illegible (18% from
      ophthalmologists vs. 6% from optometrists; P< 0.01). Degree of urgency was
      mentioned in 27% of referrals. Optometrists were more likely than
      ophthalmologists to provide visual acuity (VA), IOP, refraction, and VFs (P< 0.01
      for each). Some 24% of referrals for progression included more than 10 of the 14
      information points suggested by the Canadian glaucoma guidelines, and 34%
      included fewer than 8 of the 14 points. CONCLUSIONS: Referral letters frequently
      did not include important information, with 34% of referral letters deemed
      substandard. Optometrist referrals were better than ophthalmologist referrals in
      terms of content and legibility. A checklist of clinical details for referring
      physicians is suggested, which includes maximum and current IOP, disc evaluation,
      serial VFs, and serial disc imaging.

PMID- 24140114
TI  - Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the
      pathogenesis of common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized
      by antibody deficiency, poor humoral response to antigens, and recurrent
      infections. To investigate the molecular cause of CVID, we carried out exome
      sequence analysis of a family diagnosed with CVID and identified a heterozygous
      frameshift mutation, c.2564delA (p.Lys855Serfs(*)7), in NFKB2 affecting the C
      terminus of NF-kappaB2 (also known as p100/p52 or p100/p49). Subsequent screening
      of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second
      heterozygous nonsense mutation, c.2557C>T (p.Arg853(*)), in one simplex case.
      Affected individuals in both families presented with an unusual combination of
      childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune
      features, and adrenal insufficiency. NF-kappaB2 is the principal protein involved
      in the noncanonical NF-kappaB pathway, is evolutionarily conserved, and functions
      in peripheral lymphoid organ development, B cell development, and antibody
      production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype
      with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot
      analysis and immunofluorescence microscopy of transformed B cells from affected
      individuals show that the NFKB2 mutations affect phosphorylation and proteasomal
      processing of p100 and, ultimately, p52 nuclear translocation. These findings
      describe germline mutations in NFKB2 and establish the noncanonical NF-kappaB
      signaling pathway as a genetic etiology for this primary immunodeficiency
      syndrome. 

PMID- 24140118
TI  - A comparison of three brain atlases for MCI prediction.
AB  - BACKGROUND: Although previous voxel-based studies using features extracted by
      atlas-based parcellation produced relatively poor performances on the prediction
      of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI),
      classification performance usually depends on features extracted from the
      original images by atlas-based parcellation. To establish whether classification
      performance differs depending on the choice of atlases, support vector machine
      (SVM)-based classification using different brain atlases was performed. NEW
      METHOD: Seventy-seven three-dimensional T1-weighted MRI data sets of subjects
      with amnestic MCI, including 39 subjects who developed AD (MCI-C) within three
      years and 38 who did not (MCI-NC), were used for voxel-based morphometry (VBM)
      analyses and analyzed using SVM-based pattern recognition methods combined with a
      feature selection method based on the SVM recursive feature elimination (RFE)
      method. Three brain atlases were used for the feature selections: the Automated
      Anatomical Labeling (AAL) Atlas, Brodmann's Areas (BA), and the LONI
      Probabilistic Brain Atlas (LPBA40). RESULTS: The VBM analysis showed a
      significant cluster of gray matter density reduction, located at the left
      hippocampal region, in MCI-C compared to MCI-NC. The SVM analyses with the SVM
      RFE algorithm revealed that the best classification performance was achieved by
      LPBA40 with 37 selected features, giving an accuracy of 77.9%. The overall
      performance in LPBA40 was better than that of AAL and BA regardless of the number
      of selected features. CONCLUSIONS: These results suggest that feature selection
      is crucial to improve the classification performance in atlas-based analysis and
      that the choice of atlases is also important.

PMID- 24140117
TI  - Risk factors for amblyopia in the vision in preschoolers study.
AB  - OBJECTIVE: To evaluate risk factors for unilateral amblyopia and for bilateral
      amblyopia in the Vision in Preschoolers (VIP) study. DESIGN: Multicenter, cross
      sectional study. PARTICIPANTS: Three- to 5-year-old Head Start preschoolers from
      5 clinical centers, overrepresenting children with vision disorders. METHODS: All
      children underwent comprehensive eye examinations, including threshold visual
      acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP
      certified optometrists and ophthalmologists who were experienced in providing
      care to children. Monocular threshold VA was tested using a single-surround HOTV
      letter protocol without correction, and retested with full cycloplegic correction
      when retest criteria were met. Unilateral amblyopia was defined as an interocular
      difference in best-corrected VA of 2 lines or more. Bilateral amblyopia was
      defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and
      worse than 20/40 for 4- to 5-year-olds. MAIN OUTCOME MEASURES: Risk of amblyopia
      was summarized by the odds ratios and their 95% confidence intervals estimated
      from logistic regression models. RESULTS: In this enriched sample of Head Start
      children (n = 3869), 296 children (7.7%) had unilateral amblyopia, and 144
      children (3.7%) had bilateral amblyopia. Presence of strabismus (P<0.0001) and
      greater magnitude of significant refractive errors (myopia, hyperopia,
      astigmatism, and anisometropia; P<0.00001 for each) were associated independently
      with an increased risk of unilateral amblyopia. Presence of strabismus, hyperopia
      of 2.0 diopters (D) or more, astigmatism of 1.0 D or more, or anisometropia of
      0.5 D or more were present in 91% of children with unilateral amblyopia. Greater
      magnitude of astigmatism (P<0.0001) and bilateral hyperopia (P<0.0001) were
      associated independently with increased risk of bilateral amblyopia. Bilateral
      hyperopia of 3.0 D or more or astigmatism of 1.0 D or more were present in 76% of
      children with bilateral amblyopia. CONCLUSIONS: Strabismus and significant
      refractive errors were risk factors for unilateral amblyopia. Bilateral
      astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia.
      Despite differences in selection of the study population, these results validated
      the findings from the Multi-Ethnic Pediatric Eye Disease Study and Baltimore
      Pediatric Eye Disease Study.

PMID- 24140120
TI  - [Characterization of inborn errors of intermediary metabolism in mexican
      patients].
AB  - INTRODUCTION: Inborn errors of intermediary metabolism (IEiM) are a group of
      heterogeneous genetic diseases that are diagnostically challenging and cause
      significant morbidity and mortality. The aim of this study is to perform a
      descriptive analysis of the number, type, and clinical features, in a series of
      cases with IEiM identified through selective diagnosis in a highly specialized
      pediatric hospital. MATERIALS AND METHODS: A retrospective study was performed
      from January of 2000 to December of 2012 by analyzing the files of 204 patients
      with an IEiM, by selective screening, before and after the implementation of
      tandem mass spectrometry (MS/MS). RESULTS: A total of 25 different types of IEiM
      were found in the 204 files; 102 organic acidurias, 100 aminoacidopathies, and 2
      fatty acid oxidation disorders. The introduction of MS/MS increased the number of
      cases detected by 50%. Patients were referred from 13 different specialists, with
      pediatricians being the most active. The average interval between onset of
      symptoms and diagnosis was 18 months. CONCLUSION: Among the sick Mexican children
      studied, a wide variety of IEiM was found, propionate defects and maple syrup
      urine disease being noteworthy. The diagnosis of metabolic disease was delayed in
      the population studied. These results present evidence to perhaps incorporate
      IEiM into an expanded newborn screening, or else to perform selective diagnosis
      in all hospitalized children with suggestive clinical data.

PMID- 24140119
TI  - Relationships between electrochemical skin conductance and kidney disease in Type
      2 diabetes.
AB  - BACKGROUND: SUDOSCAN(r) non-invasively measures peripheral small fiber and
      autonomic nerve activity using electrochemical skin conductance. Since neuropathy
      and nephropathy are microvascular Type 2 diabetes (T2D) complications,
      relationships between skin conductance, estimated glomerular filtration rate
      (eGFR), and urine albumin:creatinine ratio (UACR) were assessed. METHODS: Two
      hundred five African Americans (AA) with T2D, 93 AA non-diabetic controls, 185
      European Americans (EA) with T2D, and 73 EA non-diabetic controls were evaluated.
      Linear models were fitted stratified by population ancestry and T2D, adjusted for
      covariates. RESULTS: Relative to EA, AA had lower skin conductance (T2D cases
      p<0.0001; controls p<0.0001). Skin conductance was also lower in T2D cases vs.
      controls in each population (p<0.0001, AA and EA). Global skin conductance was
      significantly associated with eGFR in AA and EA with T2D; adjusting for age,
      gender, BMI, and HbA1c, positive association was detected between skin
      conductance and eGFR in AA T2D cases (parameter estimate 3.38, standard error
      1.2; p=5.2E(-3)), without association in EA T2D cases (p=0.22). CONCLUSIONS:
      Noninvasive measurement of skin conductance strongly associated with eGFR in AA
      with T2D, replicating results in Hong Kong Chinese. SUDOSCAN(r) may prove useful
      as a low cost, non-invasive screening tool to detect undiagnosed diabetic kidney
      disease in populations of African ancestry.

PMID- 24140121
TI  - Single infusion of donor mononuclear early apoptotic cells as prophylaxis for
      graft-versus-host disease in myeloablative HLA-matched allogeneic bone marrow
      transplantation: a phase I/IIa clinical trial.
AB  - Because of its potent immunomodulatory effect, an infusion of donor mononuclear
      early apoptotic cells (ApoCell) was tested in addition to cyclosporine and
      methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA
      matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT)
      from a related donor. In a phase I/IIa clinical trial, we treated 13 patients
      (median age, 37 years; range, 20 to 59 years) with hematologic malignancies: 7
      patients with acute lymphoblastic leukemia, 5 patients with acute myeloid
      leukemia, and 1 patient with chronic myeloid leukemia, who received conventional
      myeloablative conditioning, with 35, 70, 140, or 210 * 10(6) cell/kg of donor
      ApoCell, on day -1 of transplantation. Engraftment was successful in all patients
      with median time to neutrophil recovery of 13 days (range, 11 to 19), and
      platelet recovery of 15 days (range, 11 to 59). Serious adverse effects were
      reported on 10 occasions in the trial, all of which were considered unrelated (n
      = 7) or unlikely to be related (n = 3) to ApoCell infusion. The nonrelapse
      mortality at day 100 and 180 after transplantation was 7.7% and the overall
      survival at 100 and 180 days after transplantation was 92% and 85%, respectively.
      All ApoCell preparations showed an in vitro significant tolerogenic effect upon
      interaction with dendritic cells. The overall incidence of acute grades II to IV
      GVHD was 23%, whereas among those receiving the 2 higher doses (n = 6), the rate
      was 0%. These results suggest that a single infusion of donor ApoCell in HLA
      matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute
      GVHD occurring after myeloablative conditioning. No dose limiting toxicity was
      observed. (Clinicaltrials.gov no. NCT00524784).

PMID- 24140122
TI  - Reduced IL-7 responsiveness defined by signal transducer and activator of
      transcription 5 phosphorylation in T cells may be a marker for increased risk of
      developing cytomegalovirus disease in patients after hematopoietic stem cell
      transplantation.
AB  - Cytomegalovirus (CMV) reactivation may lead to CMV disease associated with high
      morbidity and mortality in patients after hematopoietic stem cell transplantation
      (HSCT); the identification of clinically relevant markers may aid in the
      identification of patients at increased risk for developing CMV-associated
      complications. We evaluated the phosphorylation of signal transducer and
      activator of transcription 5 (STAT5) in CD4(+) T cells, CD8(+) T cells, and
      TCRgammadelta T cells in response to stimulation with IL-7 or IL-2 after HSCT by
      analyzing blood samples taken monthly 1 to 6 months after HSCT. Patients were
      monitored weekly with a quantitative PCR from the time of engraftment for CMV
      viral load in whole blood until at least day 100 after HSCT. We identified a
      correlation between clinical outcome regarding CMV replication and the ability to
      respond to IL-7 and IL-2 defined by STAT5 phosphorylation (pSTAT5). Patients with
      recurrent or prolonged CMV replications had significantly lower pSTAT5 upon
      stimulation of T cells with either IL-7 or IL-2 at time points 1 through 3 than
      those without CMV replication (P < .05). This was also found after stimulation of
      CD8(+) T cells at time point 2 (P < .05). We conclude that reduced responses to
      IL-7, reflected by pSTAT5, may represent a clinically relevant functional
      biomarker for individuals at increased risk for CMV reactivation; our data may
      also aid in designing better strategies to improve anti-CMV immune responses
      without increasing the risk of developing graft-versus-host disease.

PMID- 24140123
TI  - Intravenous versus oral busulfan-based conditioning for pediatric allogeneic
      hematopoietic cell transplantations: did the pendulum swing too far, too fast?

PMID- 24140125
TI  - A Colpoda aspera isolate from animal faeces: In vitro cultivation and
      identification.
AB  - A colpodean ciliate was found in the faeces of experimental rabbits. It was
      initially cultivated in medium mixed with 2% (w/v) rabbit faeces. Subsequently,
      two chemically defined media, designated CA-1 and CA-2, were found to be suitable
      for axenical cultivation of the ciliate. The maximum abundance of the ciliate
      isolate in the CA media was 1-2 * 10(5) cells/ml. The ciliate isolate was further
      identified with silver impregnation and molecular analysis. Features of the left
      oral polykinetid, somatic dikinetids, and sliverline pattern were similar to
      those of Colpoda aspera as described by Foissner (1993). The 18S small subunit
      ribosomal RNA gene of the ciliate isolate shared 99% sequence identity with that
      of C. aspera, with 100% coverage, and formed a sister clade in the phylogenetic
      tree with the reference C. aspera isolate. In addition, the trophozoite of C.
      aspera could proliferate over a temperature range from 25-37 degrees C. When
      resting cysts were cultivated in CA-1 medium at 30-35 degrees C, 98.2% of the
      trophozoites were detached from the cyst wall after 7 h.

PMID- 24140126
TI  - Transcriptome analysis of the exocarp of apple fruit identifies light-induced
      genes involved in red color pigmentation.
AB  - Although the mechanism of light regulation of color pigmentation of apple fruit
      is not fully understood, it has been shown that light can regulate expression of
      genes in the anthocyanin biosynthesis pathway by inducing transcription factors
      (TFs). Moreover, expression of genes encoding enzymes involved in this pathway
      may be coordinately regulated by multiple TFs. In this study, fruits on trees of
      apple cv. Red Delicious were covered with paper bags during early stages of fruit
      development and then removed prior to maturation to analyze the transcriptome in
      the exocarp of apple fruit. Comparisons of gene expression profiles of fruit
      covered with paper bags (dark-grown treatment) and those subjected to 14 h light
      treatment, following removal of paper bags, were investigated using an apple
      microarray of 40,000 sequences. Expression profiles were investigated over three
      time points, at one week intervals, during fruit development. Overall, 736 genes
      with expression values greater than two-fold were found to be modulated by light
      treatment. Light-induced products were classified into 19 categories with highest
      scores in primary metabolism (17%) and transcription (12%). Based on the
      Arabidopsis gene ontology annotation, 18 genes were identified as TFs. To further
      confirm expression patterns of flavonoid-related genes, these were subjected to
      quantitative RT-PCR (qRT-PCR) using fruit of red-skinned apple cv. Red Delicious
      and yellow-skinned apple cv. Golden Delicious. Of these, two genes showed higher
      levels of expression in 'Red Delicious' than in 'Golden Delicious', and were
      likely involved in the regulation of fruit red color pigmentation.

PMID- 24140124
TI  - Mitochondrial DNA sequence associations with dementia and amyloid-beta in elderly
      African Americans.
AB  - Mitochondrial dysfunction occurs early in the course of several neurodegenerative
      diseases, and is potentially related to increased oxidative damage and amyloid
      beta (Abeta) formation in Alzheimer's disease. The goals of this study were to
      assess mtDNA sequence associations with dementia risk, 10-year cognitive change,
      and markers of oxidative stress and Abeta among 1089 African-Americans in the
      population-based Health, Aging, and Body Composition Study. Participants were
      free of dementia at baseline, and incidence was determined in 187 (18%) cases
      over 10 to 12 follow-up years. Haplogroup L1 participants were at increased risk
      for developing dementia (odds ratio = 1.88, 95% confidence interval = 1.23-2.88,
      p = 0.004), lower plasma Abeta42 levels (p = 0.03), and greater 10-year decline
      on the Digit Symbol Substitution Test (p = 0.04) when compared with common
      haplogroup L3. The p.V193I, ND2 substitution was associated with significantly
      higher Abeta42 levels (p = 0.0012), and this association was present in
      haplogroup L3 (p = 0.018) but not L1 (p = 0.90) participants. All associations
      were independent of potential confounders, including APOEepsilon4 status and
      nuclear genetic ancestry. Identification of mtDNA sequence variation associated
      with dementia risk and cognitive decline may contribute to the development of new
      treatment targets and diagnostic tests that identify responders to interventions
      targeting mitochondria.

PMID- 24140127
TI  - Negative regulation of the peptidylarginine deiminase type IV promoter by NF
      kappaB in human myeloid cells.
AB  - High titers of anti-citrullinated protein/peptide antibodies (ACPAs) have been
      detected in sera of rheumatoid arthritis (RA) patients, implicating
      citrullinating enzymes in the pathogenesis of RA. Peptidylarginine deiminase type
      IV (PAD4) is a member of the PAD family of citrullinating enzymes and has been
      linked to RA. Therefore, our aim was to determine how transcription of PAD4 is
      regulated in the human myeloid lineage. We located the PAD4 transcription start
      site and promoter and phylogenetic comparisons of the area identified a 200 bp
      conserved region. Bioinformatics analysis predicted the presence of a NF-kappaB
      binding site and we tested this via luciferase assays. Intriguingly, mutation of
      the predicted NF-kappaB site significantly increased biological activity. We used
      RT-qPCR to quantify PAD4 expression in HL-60 cells treated with TNF-alpha to
      activate the canonical NF-kappaB pathway and found that PAD4 mRNA was reduced in
      response to TNF-alpha treatment. Finally, we used chromatin immunoprecipitation
      (ChIP) to determine NF-kappaB enrichment at the PAD4 promoter and the p50 subunit
      of NF-kappaB was more highly enriched than p65 at the PAD4 promoter. These
      results suggest that the p50 subunit of NF-kappaB may play a role in the
      repression of PAD4 transcription during inflammation.

PMID- 24140128
TI  - Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue
      to cover wounds after colorectal endoscopic submucosal dissection (with video).
AB  - BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) has made it
      possible to resect large specimens in an en bloc fashion. However, this can lead
      to postoperative adverse events, such as perforation and bleeding. Prevention of
      adverse events after colorectal ESD is therefore an important goal. OBJECTIVE: To
      evaluate the utility of a shielding method using polyglycolic acid (PGA) sheets
      and fibrin glue to manage ulcers after colorectal ESD. DESIGN: Prospective,
      single-arm, pilot study. SETTING: Single tertiary care center for colorectal ESD
      in Japan. PATIENTS: Ten patients with 10 colorectal tumors scheduled for ESD were
      enrolled between September and November 2012. INTERVENTIONS: Just after ESD, we
      placed PGA sheets on the mucosal defect with biopsy forceps. After the whole
      defect was covered, we sprayed fibrin glue through a special double-lumen
      spraying tube. We sprayed fibrinogen through 1 lumen and then thrombin through
      the other lumen. MAIN OUTCOME MEASUREMENTS: Success rate, mean procedure time,
      and adverse events associated with the covering technique and the persistence of
      PGA sheets at follow-up colonoscopy. RESULTS: All 10 tumors were successfully
      resected. Mean tumor size was 39.7 +/- 15.2 mm. All mucosal defects were
      successfully covered with PGA sheets. Mean procedure time was 18.7 +/- 15.9
      minutes. No procedure-related adverse events occurred. Upon colonoscopy 9 to 12
      days after ESD, the PGA sheets were still fixed on the whole defect in 8
      patients. LIMITATIONS: Small sample size. CONCLUSIONS: Our technique, which uses
      PGA sheets and fibrin glue, appears to shield mucosal defects, and it may be
      effective in reducing postoperative adverse events.

PMID- 24140129
TI  - Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary
      sclerosing cholangitis: a systematic review and meta-analysis.
AB  - BACKGROUND: The most ominous adverse event of primary sclerosing cholangitis
      (PSC) is development of cholangiocarcinoma (CCA). There is a wide variation in
      the reported diagnostic yield of bile duct brush cytology in PSC strictures.
      OBJECTIVE: To determine the diagnostic utility of biliary brush cytology for CCA
      detection in patients with PSC. DESIGN: Meta-analysis. Systematic search of
      PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies
      published up to December 2012. SETTING: Meta-analysis of diagnostic parameters.
      PATIENTS: A total of 747 patients in studies (both retrospective and prospective)
      in which histopathologic correlation of CCA was available. INTERVENTION: Meta
      analysis. Construction of 2 * 2 contingency data. MAIN OUTCOME MEASUREMENTS:
      Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio.
      RESULTS: The search yielded 54 studies of which 11, involving 747 patients, were
      included in our meta-analysis. The pooled sensitivity and specificity of bile
      duct brushings for a diagnosis of CCA in patients with PSC were 43% (95%
      confidence interval [CI], 35%-52%) and 97% (95% CI, 95%-98%), respectively. The
      pooled diagnostic odds ratio to detect CCA was 20.23 (95% CI, 8.75-46.79). The
      heterogeneity indices of chi(2) statistics, I(2) measure of inconsistency, and
      the Cochran Q test were 0.156, 14.4, and 30.5%, respectively. Visual inspection
      of the funnel plot showed low potential for publication bias. LIMITATIONS:
      Inclusion of low-quality studies, study heterogeneity. CONCLUSION: Our study
      suggests that bile duct brushing is a simple and highly specific technique for
      detection of CCA in patients with PSC. However, the modest sensitivity from bile
      duct brushing precludes its utility as a diagnostic tool for early detection of
      CCA in patients with PSC.

PMID- 24140130
TI  - Cryotherapy for treatment of radiation proctitis.

PMID- 24140131
TI  - Evaluation of the stability of enterovirus 71 virus-like particle.
AB  - Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth
      disease that caused significant mortality in children, but no vaccine is
      available yet. EV71 virus-like particle (VLP) is the empty capsid consisting of
      viral structural proteins but can elicit potent immune responses, rendering VLP a
      promising EV71 vaccine candidate. To evaluate whether VLP remains stable after
      long-term storage, which is crucial for advancing the VLP vaccine to the clinical
      setting, we evaluated the effects of NaCl concentration, buffers and temperatures
      on the VLP stability. We first validated the use of dynamic light scattering
      (DLS) for measuring the hydrodynamic diameter (~30-35 nm) of VLP, which was close
      to the VLP diameter (~25-27 nm) as measured by transmission electron microscopy
      (TEM). Using these techniques, we found that EV71 VLP remained stable for 5
      months in sodium phosphate (NaPi) buffers with various NaCl concentrations. EV71
      VLP also remained morphologically stable in NaPi, citrate and TE(+) buffers for 5
      months, yet the enzyme-linked immunosorbent assay (ELISA) revealed that the VLP
      stored in citrate and TE(+) buffers partially lost the immunogenicity after 5
      months. In contrast, the VLP stored in the NaPi buffer at 4 degrees C remained
      stable macroscopically and microscopically for 5 months, as judged from the DLS,
      TEM and ELISA. The VLP stored at 25 degrees C and 37 degrees C also retained
      stability for 1 month, which would obviate the need of a cold chain during the
      shipping. These data altogether proved the stability of EV71 VLP and suggested
      that the VLP is amenable to bioprocessing and storage.

PMID- 24140132
TI  - Premature preterm rupture of the membrane diagnosis in early pregnancy: PAMG-1
      and IGFBP-1 detection in amniotic fluid with biochemical tests.
AB  - OBJECTIVES: Previable premature rupture of the membranes (pPROM), occurring
      before 24WG, is associated with a 25% neonatal survival rate. This terrible
      prognosis may lead to elective pregnancy termination on parents' request.
      Therefore, certain diagnosis is essential but remains difficult in about 10% of
      patients. Bed-side biochemical tests developed to help in diagnosis had never
      been evaluated in early pregnancies. This study aimed to evaluate and compare the
      in vitro sensitivity, detection limit, reaction time and consistency of AmniSure
      detecting placental alpha microglobulin-1 (PAMG-1) and actim PROM detecting
      Insulin Growth Factor Binding Protein-1 (IGFBP-1) in amniotic fluid between 15
      and 20weeks of gestation (WG). DESIGN AND METHODS: Samples of amniotic fluid were
      collected by amniocentesis performed between 15 and 20 completed WG in 55
      patients. Dilution series were prepared and both tests were performed twice at
      each dilution. In vitro sensitivity, detection limit, and reaction time were
      evaluated and compared in serial dilution. RESULTS: A total of 460 AmniSure and
      476 actim PROM tests were performed. Both tests' in vitro sensitivity was 100% at
      dilution 1:20 and remained up to 90% until dilution 1:80. In vitro sensitivities
      were not different at any dilution. Detection limit and consistency were similar
      for both tests at all dilution. Actim PROM reaction time was shorter than
      AmniSure at all dilutions, except 1:320 (p<0.05). CONCLUSIONS: PAMG-1 and IGFBP-1
      can be detected in amniotic fluid between 15 and 20 completed WG, using
      respectively AmniSure and actim PROM.

PMID- 24140133
TI  - Coronary artery perforations: four different cases and a review.
AB  - Coronary artery perforation (CAP) is a rare but feared complication of
      percutaneous coronary intervention. With the advent of new devices and
      technologies, interventionalists attempt more complex lesions, including more
      calcified or tortuous vessels and chronic total occlusions, which increases the
      incidence of CAP. A short literature review, in addition to four cases of CAP, is
      presented in this report. 

PMID- 24140134
TI  - Thrombotic myocardial infarction with aspiration of large thrombi.

PMID- 24140135
TI  - Cell cycle, differentiation and disease.

PMID- 24140136
TI  - Patient and caregiver quality of life in psychogenic non-epileptic seizures
      compared to epileptic seizures.
AB  - PURPOSE: Little is known about the effect of psychogenic non epileptic seizures
      (PNES) to caregiver quality of life (QOL), particularly as it compares to
      epileptic seizures (ES). We sought to characterize this effect and identify its
      determinants. METHODS: The study population comprised of 126 ES and 33 PNES
      patients who underwent video EEG monitoring along with 48 and 18 caregivers
      respectively who accompanied them to their investigations. Patients completed
      questionnaires providing demographic, disease-related, cognitive, psychiatric,
      sleep and QOL information on admission, prior to their diagnosis being clarified.
      Their caregivers completed questionnaires providing demographic, disease burden
      and generic QOL information. Paraclinical data were also gathered. Regression
      analysis was used to identify patient and caregiver related determinants of
      patient and caregiver QOL. RESULTS: QOL scores were significantly worse for PNES
      than ES patients and were mainly linked to depression levels. PNES and ES
      caregivers had comparable demographic characteristics and QOL scores. ES
      caregiver QOL was better in employed caregivers with lower burden scores for the
      physical component summary (PCS) and worse in female caregivers of depressed
      patients with higher burden scores for the mental component summary (MCS).
      Caregiver burden score was the strongest correlate of PNES caregiver MCS QOL
      score. CONCLUSION: Caregiver QOL in PNES does not differ from caregiver QOL in
      ES, while patient QOL is worse in PNES. Caregiver burden emerges as a consistent
      correlate of caregiver QOL both in ES and PNES. These findings advocate for
      consideration of caregiver burden and QOL in PNES in clinical practice and for
      future research paradigms.

PMID- 24140137
TI  - The toxicity of 3-chloropropane-1,2-dipalmitate in Wistar rats and a metabonomics
      analysis of rat urine by ultra-performance liquid chromatography-mass
      spectrometry.
AB  - 3-Monochloropropane-1,2-diol(3-MCPD) fatty acid esters can release free 3-MCPD in
      a certain condition. Free 3-MCPD is a well-known food contaminant and is
      toxicological well characterized, however, in contrast to free 3-MCPD, the
      toxicological characterization of 3-MCPD fatty acid esters is puzzling. In this
      study, toxicological and metabonomics studies of 3-chloropropane-1,2
      dipalmitate(3-MCPD dipalmitate) were carried out based on an acute oral toxicity
      test, a 90-day feeding test and ultra-performance liquid chromatography-mass
      spectrometry (UPLC-MS) analysis. The LD50 value of 3-MCPD dipalmitate was
      determined to be 1780 mg/kg body weight (bw) for Wistar rats. The results of the
      90-day feeding test in male Wistar rats showed that 3-MCPD dipalmitate caused a
      significant increase in blood urea nitrogen and creatinine in the high-dose group
      (267 mg/kg bw/day) compared to control rats. Renal tubular epithelium cell
      degeneration and renal tubular hyaline cast accumulation were the major
      histopathological changes in rats administered 3-MCPD dipalmitate. Urine samples
      obtained after the 90-day feeding test and analyzed by UPLC-MS showed that the
      differences in metabolic profiles between control and treated rats were clearly
      distinguished by partial least squares-discriminant analysis (PLS-DA) of the
      chromatographic data. Five metabolite biomarkers which had earlier and
      significant variations had been identified, they were first considered to be the
      early, sensitive biomarkers in evaluating the effect of 3-MCPD dipalmitate
      exposure, and the possible mechanism of these biomarkers variation was
      elucidated. The combination of histopathological examination, clinical chemistry
      and metabolomics analyses in rats resulted in a systematic and comprehensive
      assessment of the long-term toxicity of 3-MCPD dipalmitate.

PMID- 24140138
TI  - Neonatal sepsis: progress towards improved outcomes.
AB  - Neonates are predisposed to infections during the perinatal period due to
      multiple exposures and a relatively compromised immune system. The burden of
      disease attributed to neonatal infections varies by geographic region and
      maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4
      million neonatal deaths annually are the consequence of invasive infections. Risk
      factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic
      immaturity, maternal Group B streptococcal colonization, prolonged rupture of
      membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial
      prophylaxis administered to GBS-colonized women has reduced the burden of disease
      associated with early onset GBS invasive infections. Active surveillance has
      identified Gram-negative pathogens as an emerging etiology of early-onset
      invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram
      positive organisms, including coagulase negative Staphylococci and Staphylococcus
      aureus, is associated with increased morbidity and mortality among premature
      infants. Invasive candidiasis is an emerging cause of late-onset sepsis,
      especially among infants who receive broad spectrum antimicrobial agents.
      Prophylactic fluconazole administration to very low birthweight (VLBW) neonates
      during the first 6 weeks of life reduces invasive candidiasis in neonatal
      intensive care units with high rates of fungal infection. Prevention of
      healthcare associated infections through antimicrobial stewardship, limited
      steroid use, early enteral feeding, limited use of invasive devices and
      standardization of catheter care practices, and meticulous hand hygiene are
      important and cost-effective strategies for reducing the burden of late-onset
      neonatal sepsis. 

PMID- 24140139
TI  - Endoscopic repair of full-thickness abductor tendon tears: surgical technique and
      outcome at minimum of 1-year follow-up.
AB  - PURPOSE: The purpose of this study was to assess the surgical outcomes of
      endoscopically repaired full-thickness abductor tendon tears using validated
      outcome measures. METHODS: After institutional review board approval was
      obtained, clinical outcome data were retrospectively collected from patients who
      underwent endoscopic gluteus medius and/or minimus repair by a single surgeon
      between August 2009 and September 2011. With a minimum follow-up of 1 year,
      patients were evaluated using the modified Harris Hip Score and the validated Hip
      Outcome Score (HOS). The HOS questionnaire included 2 subsections: HOS-Activities
      of Daily Living and HOS-Sports. Physical examination data were gathered during
      routine clinic visits, 1 year postoperatively. Statistical analysis was
      descriptive. The change in strength testing postoperatively was assessed with the
      Wilcoxon signed rank test, with significance set at P <= .05. RESULTS: Twelve
      patients were identified, 1 of whom was excluded; 10 of 11 patients (91%)
      completed the study requirements. The mean patient age was 65.9 years (range, 60
      to 74 years), 70% were women, and the mean follow-up period was 23 months (range,
      13 to 38 months). The mean postoperative scores were 84.7 (SD, 14.5) for the
      modified Harris Hip Score and 89.1 (SD, 11.3) for the HOS-Activities of Daily
      Living, with 90% patient satisfaction. All patients had clinically and
      statistically improved abductor tendon strength (P = .004). Patients with good to
      excellent outcomes were younger (P < .001). There were no complications
      identified. CONCLUSIONS: In our small series, endoscopic abductor tendon repair
      was an effective surgical intervention after failed conservative management at
      short-term follow-up. Patients had reliably good to excellent outcomes with
      improved strength during hip abduction, were at low risk of complications, and
      were satisfied with the outcome. In addition, younger patients achieved better
      outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24140140
TI  - Single-bundle anterior cruciate ligament reconstruction: a biomechanical
      cadaveric study of a rectangular quadriceps and bone--patellar tendon--bone graft
      configuration versus a round hamstring graft.
AB  - PURPOSE: The purposes of this study were to investigate anterior tibial
      translation under loading conditions after single-bundle (SB) anterior cruciate
      ligament (ACL) reconstruction using a rectangular tunnel placement strategy with
      quadriceps and bone--patellar tendon--bone (BPTB) graft and to compare these data
      with a SB hamstring reconstruction with a round tunnel design. METHODS: In 9
      human cadaveric knees, the knee kinematics were examined with robotic/universal
      force-moment sensor testing. Within the same specimen, the knee kinematics under
      simulated pivot-shift and KT-1000 arthrometer (MEDmetric, San Diego, CA) testing
      were determined at 0 degrees , 15 degrees , 30 degrees , 60 degrees , and 90
      degrees  of flexion under different conditions: intact knee, ACL-deficient knee,
      and SB ACL-reconstructed knee. For the SB ACL-reconstructed knee, 3 different SB
      reconstruction techniques were used: a rectangular tunnel strategy (9 * 5 mm)
      with quadriceps graft, a rectangular tunnel strategy with BPTB graft, and a round
      tunnel strategy (7 mm) with hamstring graft. RESULTS: In a simulated Lachman
      test, a statistically significant difference was found at 0 degrees  and 15
      degrees  of knee flexion between the rectangular reconstruction with quadriceps
      graft (5.1 +/- 1.2 mm and 8.3 +/- 2 mm, respectively) or BPTB graft (5.3 +/- 1.5
      mm and 8 +/- 1.9 mm, respectively) and the reconstruction using hamstring graft
      (7.2 +/- 1.4 mm and 12 +/- 1.8 mm, respectively) (P = .032 and P = .033,
      respectively, at 0 degrees ; P = .023 and P = .02, respectively, at 15 degrees ).
      On the simulated pivot-shift test at 0 degrees  and 15 degrees , rectangular ACL
      reconstruction with quadriceps graft (3.9 +/- 2.1 mm and 6.5 +/- 1.7 mm,
      respectively) or BPTB graft (4.2 +/- 1.8 mm and 6.7 +/- 1.7 mm, respectively)
      showed a significantly lower anterior tibial translation when compared with round
      tunnel reconstruction (5.5 +/- 2.1 mm and 7.9 +/- 1.9 mm, respectively) (P = .03
      and P = .041, respectively, at 0 degrees ; P = .042 and P = .046, respectively,
      at 15 degrees ). CONCLUSIONS: Under simulated Lachman testing and pivot-shift
      testing, a reconstruction technique using a rectangular tunnel results in
      significantly lower anterior tibial translation at 0 degrees  and 15 degrees  of
      flexion in comparison to knees reconstructed with a hamstring SB graft using a
      round tunnel strategy. CLINICAL RELEVANCE: ACL reconstruction with a rectangular
      tunnel and BPTB and quadriceps tendon might result in better anterior knee
      stability at low flexion angles than ACL reconstruction with hamstring SB graft
      and a round tunnel in the clinical setting.

PMID- 24140141
TI  - Outside-in continuous suturing is superior to interrupted suturing for repairing
      peripheral meniscus lesions: an in vitro biomechanical study using a porcine
      model.
AB  - PURPOSE: This in vitro biomechanical study using a porcine model compared
      peripheral longitudinal vertical meniscus lesion (PLVML) outside-in suture repair
      fixation strength using either interrupted or continuous "N" configuration No. 2
      0 braided polyester sutures. METHODS: Porcine lateral menisci were randomly
      assigned to group 1 (continuous) or group 2 (interrupted). Standardized PLVMLs
      were created in each specimen. Repaired specimens were placed in a specially
      designed clamp and loaded into a servohydraulic device. Specimens underwent
      preconditioning for 10 cycles (0.1 Hz, 5 to 20 N) and 500 submaximal loading
      cycles (0.5 Hz, 5 to 20 N), before load-to-failure testing (12.5 mm/s). A 30
      second pause after preconditioning and after 10, 100, and 500 submaximal loading
      cycles enabled standardized digital photographs to be taken for gapping
      measurement determination. The failure mode was documented. RESULTS: Displacement
      and gapping during preconditioning and submaximal loading cycles did not differ
      between groups. Group 1 withstood a greater failure load (mean, 118.3 N; 95%
      confidence interval [CI], 97.2 to 139.4 N) than group 2 (mean, 63.7 N; 95% CI,
      51.2 to 76.2 N) (P < .0001) and displacement during load-to-failure testing
      (mean, 5.3 mm; 95% CI, 4.2 to 6.5 mm) than group 2 (mean, 3.2 mm; 95% CI, 2.1 to
      4.3 mm) (P = .005). Group 1 failed by suture breakage or suture pulling through
      tissue, whereas group 2 primarily failed by knot slippage (P < .0001).
      CONCLUSIONS: Group displacement and gapping differences were not observed after
      500 submaximal loading cycles. PLVMLs repaired with a continuous N configuration,
      however, withstood greater load at failure and greater displacement before
      failure than repairs that used interrupted sutures. CLINICAL RELEVANCE:
      Continuous suture in an N configuration may improve PLVML repair fixation
      strength.

PMID- 24140142
TI  - Intra-articular versus periarticular acromioclavicular joint injection: a
      multicenter, prospective, randomized, controlled trial.
AB  - PURPOSE: The purpose of this randomized study was to compare the clinical
      efficacy of intra-articular versus periarticular acromioclavicular joint
      injections. METHODS: In this multicenter, prospective, randomized, controlled
      trial, 101 patients (106 shoulders) with symptomatic acromioclavicular joints
      were treated with an injection and were randomly assigned to either the intra
      articular group or the periarticular group. To ensure accurate needle placement
      either intra-articularly or in a periarticular manner, the needle was placed
      under ultrasound guidance. Baseline values including the Constant-Murley score,
      pain assessment with a visual analog scale for pain under local pressure and pain
      at night, and the crossover arm test were investigated in 7 different centers
      immediately before treatment. Follow-up examinations were scheduled after 1 hour,
      1 week, and 3 weeks. RESULTS: All patients completed the study. Overall, a highly
      significant clinical improvement in all tested variables and in both groups was
      observed over time (P < .0001) beginning with 1 hour after treatment and lasting
      for the entire follow-up period of 3 weeks. The difference between the 2 groups
      was not significant except regarding the crossover arm test (P < .016).
      CONCLUSIONS: With both injection techniques, a highly significant clinical
      advantage for the patient can be achieved. The difference between the 2
      treatments was not significant except for more pain reduction according to the
      crossover arm test after intra-articular injection at 3 weeks' follow-up. LEVEL
      OF EVIDENCE: Level II, multicenter, randomized, prospective, controlled trial.

PMID- 24140143
TI  - Anatomic footprint of the direct head of the rectus femoris origin: cadaveric
      study and clinical series of hips after arthroscopic anterior inferior iliac
      spine/subspine decompression.
AB  - PURPOSE: The purposes of this study were to define the anatomy of the anterior
      inferior iliac spine (AIIS) and its relation to the footprint of the rectus
      femoris tendon and to evaluate on the clinical outcomes after AIIS/subspine
      decompression. METHODS: The rectus origin was dissected and detached in 11 male
      cadaveric hips with a mean age of 54.3 +/- 14.3 years (range, 33 to 74 years).
      The proximal-distal and medial-lateral extent of the footprint and its relation
      to the AIIS and acetabular rim were evaluated, with the 12-o'clock position
      defined as directly lateral at the insertion of the indirect head of the rectus
      tendon and the 1- to 6-o'clock positions defined as anterior acetabular
      positions. To assess the safety and efficacy of subspine decompression for AIIS
      deformity, clinical correlation of a series of 163 AIIS decompressions (mean age,
      27.8 years; age range, 14 to 52 years) performed from January 2011 to January
      2012 was completed, and outcome scores, strength deficits, and ruptures were
      assessed by manual muscle testing and postoperative radiographs. All patients
      presented with symptomatic FAI with proximal femoral and/or acetabular deformity
      and type 2 (131 hips) or type 3 (32 hips) AIIS morphology as defined by Hetsroni
      et al. RESULTS: The mean proximal-distal and medial-lateral distances for the
      rectus origin footprint were 2.2 +/- 0.1 cm (range, 2.1 to 2.4 cm) and 1.6 +/-
      0.3 cm (range, 1.2 to 2.3 cm), respectively. There was a characteristic bare area
      at the anteromedial AIIS. On the clock face, the lateral margin (1-o'clock to
      1:30 position) and medial margin (2-o'clock to 2:30 position) of the AIIS and the
      indirect head of the rectus (12 o'clock) were consistent for all specimens. In
      the clinical series, 163 AIIS decompressions were performed for symptomatic
      subspine impingement. The mean modified Harris Hip Score was 63.1 points (range,
      21 to 90 points) preoperatively compared with 85.3 points (range, 37 to 100
      points) at a mean follow-up of 11.1 +/- 4.1 months (range, 6 to 24 months) (P <
      .01). Short Form 12 scores improved significantly from a mean of 70.4 (range, 34
      to 93) preoperatively to a mean of 81.3 (range, 31 to 99) postoperatively (P <
      .01). The mean pain score on a visual analog scale also improved significantly
      from a mean of 4.9 (range, 0.1 to 8.6) preoperatively to a mean of 1.9 (range, 0
      to 7.8) postoperatively (P < .01). The mean alpha angle improved from 61.5
      degrees  (range, 35 degrees  to 90 degrees ) preoperatively to 49 degrees 
      (range, 35 degrees  to 63 degrees ) postoperatively on anteroposterior
      radiographs and from 71 degrees  (range, 45 degrees  to 90 degrees )
      preoperatively to 44.3 degrees  (range, 37 degrees  to 60 degrees )
      postoperatively on lateral radiographs. No short- or long-term hip flexion
      deficits or rectus femoris avulsions were noted with up to 2 years' follow-up.
      CONCLUSIONS: The origin of the rectus femoris tendon is broad on the AIIS and
      protective against direct head detachment with subspine decompression. This broad
      origin and consistent bare area anteromedially on the AIIS can be readily used by
      surgeons to perform a safe AIIS resection in cases of symptomatic impingement.
      Arthroscopic subspine decompression in addition to osteoplasty for symptomatic
      cam- and/or pincer-type FAI deformities can reliably improve outcome scores
      without significant hip flexion deficits or AIIS/rectus femoris avulsions.
      CLINICAL RELEVANCE: The direct head of the rectus tendon has a broad insertion on
      the AIIS, and an area devoid of tendon provides a "safe zone" for subspine
      decompression in cases of symptomatic AIIS impingement.

PMID- 24140145
TI  - The promise of riboswitches as potential antibacterial drug targets.
AB  - Riboswitches represent promising novel RNA structures for developing compounds
      that artificially regulate gene expression and, thus, bacterial growth. The past
      years have seen increasing efforts to identify metabolite-analogues which act on
      riboswitches and which reveal antibacterial activity. Here, we summarize the
      current inventory of riboswitch-targeting compounds, their characteristics and
      antibacterial potential. 

PMID- 24140144
TI  - The influence of hamstring autograft size on patient-reported outcomes and risk
      of revision after anterior cruciate ligament reconstruction: a Multicenter
      Orthopaedic Outcomes Network (MOON) Cohort Study.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of graft size on
      patient-reported outcomes and revision risk after anterior cruciate ligament
      (ACL) reconstruction. METHODS: A retrospective chart review of prospectively
      collected cohort data was performed, and 263 of 320 consecutive patients (82.2%)
      undergoing primary ACL reconstruction with hamstring autograft were evaluated. We
      recorded graft size; femoral tunnel drilling technique; patient age, sex, and
      body mass index at the time of ACL reconstruction; Knee Injury and Osteoarthritis
      Outcome Score (KOOS) and International Knee Documentation Committee score
      preoperatively and at 2 years postoperatively; and whether each patient underwent
      revision ACL reconstruction during the 2-year follow-up period. Revision was used
      as a marker for graft failure. The relation between graft size and patient
      reported outcomes was determined by multiple linear regression. The relation
      between graft size and risk of revision was determined by dichotomizing graft
      size at 8 mm and stratifying by age. RESULTS: After we controlled for age, sex,
      operative side, surgeon, body mass index, graft choice, and femoral tunnel
      drilling technique, a 1-mm increase in graft size was noted to correlate with a
      3.3-point increase in the KOOS pain subscale (P = .003), a 2.0-point increase in
      the KOOS activities of daily living subscale (P = .034), a 5.2-point increase in
      the KOOS sport/recreation function subscale (P = .004), and a 3.4-point increase
      in the subjective International Knee Documentation Committee score (P = .026).
      Revision was required in 0 of 64 patients (0.0%) with grafts greater than 8 mm in
      diameter and 14 of 199 patients (7.0%) with grafts 8 mm in diameter or smaller (P
      = .037). Among patients aged 18 years or younger, revision was required in 0 of
      14 patients (0.0%) with grafts greater than 8 mm in diameter and 13 of 71
      patients (18.3%) with grafts 8 mm in diameter or smaller. CONCLUSIONS: Smaller
      hamstring autograft size is a predictor of poorer KOOS sport/recreation function
      2 years after primary ACL reconstruction. A larger sample size is required to
      confirm the relation between graft size and risk of revision ACL reconstruction.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 24140146
TI  - Hemodynamic acute kidney injury in immunoglobulin A nephropathy: nephrosarca
      theory revisited.

PMID- 24140147
TI  - Quality initiative to reduce benzodiazepine use in a cardiothoracic intensive
      care unit.

PMID- 24140148
TI  - Levels of moderate--vigorous physical activity are low in Spanish children with
      cystic fibrosis: a comparison with healthy controls.
AB  - BACKGROUND: Physical activity (PA) is recommended as part of the treatment
      regimen for cystic fibrosis (CF) although objective methods have been scarcely
      used to monitor achievement of PA guidelines. METHODS: PA was measured by
      accelerometer in outpatient CF children (n=47) and results were compared with
      those obtained in age- and gender-matched healthy controls (n=39). RESULTS: 2.1%
      of the outpatients fulfilled PA guidelines (i.e. >=60min.day(-1) of moderate-to
      vigorous PA (MVPA)) vs. 34.2% of controls. Overall, lower MVPA levels were
      observed in CF patients than controls despite the former undergoing more light or
      total PA. Peak oxygen uptake was also lower in the CF group than in controls
      (37.5+/-7.8 vs. 43.5+/-7.6ml.kg(-1).min(-1), p=0.002) and was correlated with
      MVPA and vigorous PA in the former. CONCLUSIONS: These findings support a need to
      promote PA interventions (including MVPA) targeted at improving cardiorespiratory
      fitness in CF children.

PMID- 24140149
TI  - Polygalacturonases from Moniliophthora perniciosa are regulated by fermentable
      carbon sources and possible post-translational modifications.
AB  - We report the first molecular and in silico analysis of Monilophthora perniciosa
      polygalacturonases (PGs). Three MpPG genes (MpPG1, MpPG2 and MpPG3) were
      identified and analyzed at transcriptional level, by RT-qPCR, in dikaryotic M.
      perniciosa mycelium grown on solid-bran based medium and on liquid medium
      supplemented with different fermentable and non-fermentable carbon sources. The
      MpPG genes presented different expression patterns suggesting different
      individual regulation. However, all are mainly regulated by fermentable carbon
      sources (galactose and mannose). The integrated analysis of PG gene expression
      and systems biology (using MpG1 and MpG2 orthologs in Neurospora crassa, named
      NCU06961 and NCU02369, respectively) allowed identifying some possible mechanism
      of protein regulation during the necrotrophic fungal phase. MpPG1-NCU06961 and
      MpPG2-NCU02369 directly or indirectly interacted with central and highly
      connected proteins involved in protein synthesis and protein regulation
      associated to post-translational modifications, in cell wall metabolism, and in
      cellular metabolism related to energy production. This analysis also allowed the
      identification of key proteins for further studies of M. perniciosa development
      and/or for disease management, such as MpPG2, a pectin methylesterase, an
      acetolactate synthase and the small ubiquitin-like modifier SMT3-like. 

PMID- 24140150
TI  - Two conidiation-related Zn(II)2Cys6 transcription factor genes in the rice blast
      fungus.
AB  - Regulation of gene expression by transcription factors (TFs) helps plant
      pathogens to interact with the host plants and to sustain a pathogenic lifestyle
      in the environmental changes. Elucidating novel functions of TFs is, therefore,
      crucial for understanding pathogenesis mechanisms of plant pathogens. Magnaporthe
      oryzae, the rice blast pathogen, undergoes a series of developmental
      morphogenesis to complete its infection cycle. To understand TF genes implicated
      in pathogenic development of this fungus, two Zn(II)2Cys6 TF genes, MoCOD1 and
      MoCOD2, whose expression was notably induced during conidiation, were
      functionally characterized. Targeted deletion of MoCOD1 resulted in defects in
      conidiation and pathogenicity due to defects in appressorium formation and
      invasive growth within the host cells. MoCOD2 was also a critical regulator in
      conidiation and pathogenicity, but not in conidial germination and appressorium
      formation. When rice plants were inoculated with conidia of the DeltaMocod2
      mutant, rapid accumulation of dark brown granules was observed around the
      infection sites in the plant cells and no visible disease symptom was incited.
      Taken together, both MoCOD1 and MoCOD2 play important roles in conidiation and
      pathogenicity of the rice blast fungus. 

PMID- 24140151
TI  - Genome-wide analysis of pectate-induced gene expression in Botrytis cinerea:
      identification and functional analysis of putative d-galacturonate transporters.
AB  - The fungal plant pathogen Botrytis cinerea produces a spectrum of cell wall
      degrading enzymes for the decomposition of host cell wall polysaccharides and the
      consumption of the monosaccharides that are released. Especially pectin is an
      abundant cell wall component, and the decomposition of pectin by B. cinerea has
      been extensively studied. An effective concerted action of the appropriate pectin
      depolymerising enzymes, monosaccharide transporters and catabolic enzymes is
      important for complete d-galacturonic acid utilization by B. cinerea. In this
      study, we performed RNA sequencing to compare genome-wide transcriptional
      profiles between B. cinerea cultures grown in media containing pectate or glucose
      as sole carbon source. Transcript levels of 32 genes that are induced by pectate
      were further examined in cultures grown on six different monosaccharides, by
      means of quantitative RT-PCR, leading to the identification of 8 genes that are
      exclusively induced by d-galacturonic acid. Among these, the hexose transporter
      encoding genes Bchxt15 and Bchxt19 were functionally characterised. The
      subcellular location was studied of BcHXT15-GFP and BcHXT19-GFP fusion proteins
      expressed under control of their native promoter, in a B. cinerea wild-type
      strain. Both genes are expressed during growth on d-galacturonic acid and the
      fusion proteins are localized in plasma membranes and intracellular vesicles.
      Target gene knockout analysis revealed that BcHXT15 contributes to d-galacturonic
      acid uptake at pH 5~5.6. The virulence of all B. cinerea hexose transporter
      mutants tested was unaltered on tomato and Nicotiana benthamiana leaves. 

PMID- 24140152
TI  - Risk assessment of endocrine disrupting chemicals--introduction to this special
      issue.

PMID- 24140153
TI  - Lysobacter capsici AZ78 can be combined with copper to effectively control
      Plasmopara viticola on grapevine.
AB  - The bacterial genus Lysobacter represents a still underdeveloped source of
      biocontrol agents able to protect plants against pathogenic oomycetes. In this
      work the L. capsici strain AZ78 was evaluated with regard to the biological
      control of Plasmopara viticola, the causal agent of grapevine downy mildew. L.
      capsici AZ78 is able to resist copper ions and its resistance to this metal is
      probably due to the presence of genes coding for copper oxidase (copA) and copper
      exporting PIB-type ATPases (ctpA). The presence of both genes was also detected
      in other members of the Lysobacter genus. Resistance to copper allowed L. capsici
      AZ78 to be combined with a low-dose of a copper-based fungicide, leading to more
      effective control of grapevine downy mildew. Notably, prophylactic application of
      L. capsici AZ78 alone to grapevine leaves reduced downy mildew disease to the
      same degree as a copper-based fungicide. Furthermore, L. capsici AZ78 persists in
      the phyllosphere of grapevine plants and tolerates environmental stresses such as
      starvation, freezing, mild heat shock and UV light irradiation. These traits
      suggest that L. capsici AZ78 could be a suitable candidate for developing a new
      biofungicide to be used in combination with copper to control grapevine downy
      mildew. 

PMID- 24140154
TI  - Evidence that the C-terminal region is involved in the stability and
      functionality of OprM in E. coli.
AB  - In order to understand the specificity of interactions between the components of
      multidrug-resistant (MDR) efflux pumps and how they are recruited/assembled, we
      analyzed the effect of C-terminal truncation, deletion, and peptide swapping on
      the stability and functionality of OprM in Escherichia coli. The efflux activity
      of OprM was not affected by removing up to 19 amino acid residues from the C
      terminus, while depletion of more than 20 residues or disruption the 463LGGG466
      motif diminished both the stability and activity of OprM. The replacement of the
      OprM C-terminus 23 residues with the corresponding part of TolC or VceC did not
      affect the stability and the functionality of OprM. Therefore, it is confirmed
      that the C-terminal 463LGGG466 motif is one of the crucial components for the
      stability of OprM and for the functionality of the OprM-VceAB chimeric pump in
      E.coli. The results also indicate that one residue substitution on the hairpin
      domain of the membrane fusion protein (MFP) VceA could suppress the null like
      mutations on the C-terminal modified OprM. This finding will be the direct
      genetic evidence that the C-terminal domain of outer efflux protein (OEP) is
      involved in the functional assembly of OEP-MFP.

PMID- 24140155
TI  - The rrnA promoter as a tool for the improved expression of heterologous genes in
      cyanobacteria.
AB  - The regulatory sequence of ribosomal RNA A (rrnA) operon from Synechococcus
      PCC7942 was characterized using green fluorescent protein gene (gfp) as a
      reporter. The PR promoter (nt. -83 to +2) including upstream promoter element and
      P1 promoter of rrnA exhibited GFP fluorescence intensity about 30-fold higher
      than full length sequence (nt. -147 to +79). The effects of PR promoter arranged
      in tandem with consensus-sigma(70) promoter (PS) of Escherichia coli on the
      expression of gfp and opd gene encoding organophosphorus hydrolase (OPH) in
      Synechococcus were investigated. The PS-PR tandem promoter was superior to all of
      the other promoters; its GFP fluorescence intensity was a 1.8-fold increase when
      compared to PR-PR tandem promoter, a 2.5-fold, 9.5-fold and a 15-fold increase
      compared to PR, PS and promoter of tRNA(pro), respectively. The GFP from PS-PR
      tandem promoter accounted for about 12% of its total extracted proteins. OPH
      activity of Synechococcus harboring opd gene under the control of PS-PR tandem
      promoter was 738 +/- 128 units/OD730. We demonstrated that the tandem promoters
      remarkably enhanced the GFP and OPH production which were detected on SDS-PAGE
      stained with Coomassie blue. The promoter system in this study could be generally
      applied to production of valuable organic products from cyanobacteria.

PMID- 24140156
TI  - Using a Caesalpinia echinata Lam. protease inhibitor as a tool for studying the
      roles of neutrophil elastase, cathepsin G and proteinase 3 in pulmonary edema.
AB  - Acute lung injury (ALI) is characterized by neutrophil infiltration and the
      release of proteases, mainly elastase (NE), cathepsin G (Cat G) and proteinase 3
      (PR3), which can be controlled by specific endogenous inhibitors. However,
      inhibitors of these proteases have been isolated from different sources,
      including plants. For this study, CeEI, or Caesalpinia echinata elastase
      inhibitor, was purified from C. echinata (Brazil-wood) seeds after acetone
      fractionation, followed by ion exchange and reversed phase chromatographic steps.
      Characterization with SDS-PAGE, stability assays, amino acid sequencing and
      alignment with other protein sequences confirmed that CeEI is a member of the
      soybean Kunitz trypsin inhibitor family. Like other members of this family, CeEI
      is a 20 kDa monomeric protein; it is stable within a large pH and temperature
      range, with four cysteine residues forming two disulfide bridges, conserved amino
      acid residues and leucine-isoleucine residues in the reactive site. CeEI was able
      to inhibit NE and Cat G at a nanomolar range (with K(i)s of 1.9 and 3.6 nM,
      respectively) and inhibited PR3 within a micromolar range (K(i) 3.7 MUM), leading
      to hydrolysis of specific synthetic substrates. In a lung edema model, CeEI
      reduced the lung weight and pulmonary artery pressure until 180 min after the
      injection of zymosan-activated polymorphonuclear neutrophils. In experiments
      performed in the presence of a Cat G and PR3, but not an NE inhibitor, lung edema
      was reduced only until 150 min and pulmonary artery pressure was similar to that
      of the control. These results confirm that NE action is crucial to edema
      establishment and progression. Additionally, CeEI appears to be a useful tool for
      studying the physiology of pulmonary edema and provides a template for molecular
      engineering and drug design for ALI therapy.

PMID- 24140157
TI  - Headache in the elderly: characteristics in a series of 262 patients.
AB  - INTRODUCTION: Although headache prevalence decreases in patients older than 65,
      headaches are a common complaint and their different clinical and therapeutic
      features must be understood. This article analyses the clinical characteristics
      of elderly patients treated in an outpatient headache unit. METHODS: We collected
      demographic and clinical data from patients treated in a tertiary hospital
      headache unit between January 2008 and May 2013. Headaches were codified
      according to the International Classification of Headache Disorders, 2nd edition
      (ICHD-2). RESULTS: Of a total of 1868 patients treated, 262 patients (14%, 189
      women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3%
      of the total) were over 75. Headaches began after the age of 65 in only 136
      patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1
      (Migraine) and 28.7% as Group 2 (Tension-type headache). We diagnosed 58 (16%)
      secondary headaches; 26 (7.2%) were classified as Group 13 (Cranial neuralgias)
      and 23 (6.4%) in Group 14 (Other headaches). Symptomatic medication overuse was
      detected in 38 patients (14.5%). We also identified headaches considered typical
      in the elderly, including chronic migraine (41 cases), hypnic headache (6),
      occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough
      headache (1), and giant cell arteritis (2). CONCLUSIONS: Elderly patients were
      frequently treated in our outpatient headache unit. Tension-type headache was the
      most common diagnosis in this population. Geriatric headache syndromes such as
      hypnic headache or occipital neuralgia were also represented in our series.

PMID- 24140158
TI  - Should the mini-mental state examination be retired?
AB  - INTRODUCTION: Short cognitive tests are routinely used in clinical practice to
      detect and screen for cognitive impairment and dementia. These cognitive tests
      should meet minimum criteria for both applicability and psychometric qualities.
      DEVELOPMENT: The Mini-Mental State Examination (MMSE) is the most frequently
      applied short cognitive test, and the article introducing it remains a milestone
      in the history of medicine. Its main advantages are its widespread use and the
      extensive empirical evidence that supports it. However, the MMSE has important
      shortcomings, including lack of standardisation, its lack of suitability for
      illiterate subjects, the considerable effect of socio-educational variables on
      results, and its limited effectiveness for detecting cognitive impairment.
      Lastly, since the test is copyright-protected, using it is necessarily either
      costly or fraudulent. Newer available instruments do not share these shortcomings
      and have demonstrated greater diagnostic accuracy for detecting cognitive
      impairment and dementia, as well as being more cost-effective than the MMSE
      CONCLUSION: It is time to acknowledge the MMSE's important role in the history of
      medicine and grant it a deserved and honourable retirement. Its place will be
      taken by more effective instruments that require less time, are user-friendly and
      free of charge, can be applied to all individuals, and yield more equitable
      outcomes.

PMID- 24140159
TI  - Alzheimer disease and cognitive impairment associated with diabetes mellitus type
      2: associations and a hypothesis.
AB  - INTRODUCTION: Epidemiological studies have demonstrated that patients with
      diabetes mellitus have an increased risk of developing Alzheimer disease, but the
      relationship between the 2 entities is not clear. DEVELOPMENT: Both diseases
      exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal
      insulin receptor signalling and insulin resistance, oxidative stress, and
      structural abnormalities in proteins and beta-amyloid deposits. Different
      hypotheses have emerged from experimental work in the last two decades. One of
      the most comprehensive relates the microvascular damage in diabetic polyneuritis
      with the central nervous system changes occurring in Alzheimer disease. Another
      hypothesis considers that cognitive impairment in both diabetes and Alzheimer
      disease is linked to a state of systemic oxidative stress. Recently, attenuation
      of cognitive impairment and normalisation of values in biochemical markers for
      oxidative stress were found in patients with Alzheimer disease and concomitant
      diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its
      end products, and on other metabolic alterations. CONCLUSIONS: Diabetic patients
      are at increased risk for developing Alzheimer disease, but paradoxically, their
      biochemical alterations and cognitive impairment are less pronounced than in
      groups of dementia patients without diabetes. A deeper understanding of
      interactions between the pathogenic processes of both entities may lead to new
      therapeutic strategies that would slow or halt the progression of impairment.

PMID- 24140160
TI  - A fuzzy model based adaptive PID controller design for nonlinear and uncertain
      processes.
AB  - We develop a novel adaptive tuning method for classical proportional-integral
      derivative (PID) controller to control nonlinear processes to adjust PID gains, a
      problem which is very difficult to overcome in the classical PID controllers. By
      incorporating classical PID control, which is well-known in industry, to the
      control of nonlinear processes, we introduce a method which can readily be used
      by the industry. In this method, controller design does not require a first
      principal model of the process which is usually very difficult to obtain.
      Instead, it depends on a fuzzy process model which is constructed from the
      measured input-output data of the process. A soft limiter is used to impose
      industrial limits on the control input. The performance of the system is
      successfully tested on the bioreactor, a highly nonlinear process involving
      instabilities. Several tests showed the method's success in tracking, robustness
      to noise, and adaptation properties. We as well compared our system's performance
      to those of a plant with altered parameters with measurement noise, and obtained
      less ringing and better tracking. To conclude, we present a novel adaptive
      control method that is built upon the well-known PID architecture that
      successfully controls highly nonlinear industrial processes, even under
      conditions such as strong parameter variations, noise, and instabilities. 

PMID- 24140161
TI  - Familial resemblance of physical activity levels in the Portuguese population.
AB  - OBJECTIVES: Moderate to high levels of physical activity are related to positive
      health status. Parents share with their children important cultural aspects and
      beliefs related to healthy living. However, family studies show contradictory
      results for familial aggregation of physical activity. The purposes of this study
      were to assess whether physical activity shows familial aggregation in the
      Portuguese population and to disentangle the exact pattern of familial
      resemblance. DESIGN: Cross-sectional family study. METHODS: We sampled 2661
      Portuguese nuclear families (10,644 subjects) and assessed their physical
      activity using the Baecke questionnaire, including components for physical
      activity work/school, leisure-time activity, sports participation, and a total
      index of physical activity. Generalized estimating equations were used to compute
      spousal, parent-offspring and sibling correlations. RESULTS: For leisure-time
      activity and total index of physical activity, the patterns were characterized
      with spouse correlations higher than parent-offspring correlations (0.20 vs 0.12,
      p=0.001 and 0.22 vs 0.12, p=10(-4), respectively) but lower than those in
      offspring (0.20 vs 0.51, p<10(-4) and 0.22 vs 0.35, p<10(-4), respectively). For
      sports participation, the spouse correlation was higher than parent-offspring
      correlations (0.30 vs 0.18, p<10(-4)), but also higher than sibling correlations
      (0.30 vs 0.22, p<10(-4)). Finally, the physical activity work/school spouse
      correlation was higher than the sibling correlations (0.22 vs 0.12, p<10(-4)).
      CONCLUSIONS: The results support the hypothesis of familial aggregation in
      physical activity. Further, fathers and mothers had a similar influence on their
      offspring's physical activity levels irrespective of their sex, and equal sibling
      correlations point toward shared physical activity habits.

PMID- 24140162
TI  - Standard therapies versus novel therapies in Hodgkin lymphoma.
AB  - The prognostic models in Hodgkin lymphoma (HL) such as the International
      Prognostic Score (IPS), retrospectively constructed in the last twenty years from
      different cohorts of patients treated with ABVD or ABVD-equivalent regimens have
      been shown a limited predictive value on treatment outcome when applied to a
      prospective cohort of patients. In the turn of millennium a new class of
      prognostic factors has emerged, aimed to test the chemosensitivity to treatment
      in a single patient-basis, such as the minimal residual disease (MRD) assessment
      with molecular biology, or interim PET/CT performed early during treatment. The
      main challenge in the management of both early and advanced-stage HL is to
      achieve a durable remission or cure while minimizing therapy toxicity. An
      adaptive therapy strategy based on interim PET results could distinguish high
      from low-risk patients: the former with a potential benefit from an intensify
      regimen, the latter in whom treatment could be de-escalated or abbreviated for
      minimizing long-term adverse effects. Conversely, chemosensitivity evaluation in
      early-stage HL has been the underpinning of de-escalation trials aimed at
      assessing the safety and the efficacy of omitting radiotherapy in interim PET
      negative patients. Brentuximab Vedotin (BV) is a novel antibody-drug conjugate
      targeting CD30 linked to a potent synthetic antitubulin chemotherapeutic agent,
      monomethyl auristatin E (MME). BV showed an impressive activity against
      refractory/relapsed HL and now is being incorporated in a modified ABVD schedule
      in first-line treatment of HL, with promising efficacy and a low toxicity
      profile. This novel therapeutic strategy will tell us if traditional ABVD or
      BEACOPP chemotherapy could be abandoned for the brand-new targeted therapy.
      Despite the brilliant results of HL treatment, which proved able to achieve a
      long-term disease control in 80-90% of the patients, the search of new prognostic
      has continued over the last two decades and the progress of the knowledge of the
      pathobiology of HL has led to a discovery of a series of markers related to
      microenvironment of HL tissue and molecular mechanisms to escape host immune
      reaction against the tumor. The strong association between the locus A of the
      human leukocyte antigen (HLA-A) system and EBV-positive HL suggests that both an
      abnormal antigen presentation and some specific EBV antigen per se could play a
      pivotal role in the pathogenesis of cHL. In EBV+HL patients, the susceptibility
      or the resistance to develop HL depends on the HLA allele A-*01 or A-*02,
      respectively. Tumor escape mechanism to block the immune response of the host
      against the neoplastic tissue is one of the property of a recently discovered
      subset of myeloid-derived suppressor cells (MDSC) that induce tumor
      vasculogenesis and escape from immunity via T cell suppression. Initially, these
      myeloid cells were identified as granulocytes or monocytes; however, MDSC derive
      from multipotent progenitor cells that can differentiate in the tissue as
      monocyte-derived MDSC (Mo-MDSC) with a phenotype CD14+/dull and granulocyte
      derived MDSC (G-MDSC) expressing CD15 on cell surface. The latter were shown to
      produce arginase. Recent investigations suggest that MDSC present in the bone
      marrow in patients with several solid and hematological cancers in response to
      chemokine release in the tumor site are correlated with tumor-associated
      macrophages (TAM). Both TAM and MDSC have been strongly associated with a
      significantly worse prognosis in HL. As a consequence, several efforts are
      ongoing to standardize the methods to assess TAM and MDSC and prospective studies
      are being planned to validate their prognostic role. 

PMID- 24140163
TI  - Seropositivity of Toxoplasma gondii in domestic donkeys (Equus asinus) and
      isolation of T. gondii from farm cats.
AB  - Donkeys (Equus asinus) are used as both companion and working animals throughout
      the world and in some countries, their meat and milk are used for human
      consumption. Here we report the first serological survey of Toxoplasma gondii in
      donkeys in the United States. Serum samples from 373 donkeys from eight farms in
      five states were tested for T. gondii antibodies by the modified agglutination
      test (MAT). Twenty-four of 373 (6.4%) of donkeys were seropositive, with MAT
      titers ranging from 25 to >= 200. All seropositive donkeys were Miniature breed.
      Seropositivity prevalence was 7.0% in female donkeys (20/282) and 4.1% in male
      donkeys (4/91). No donkeys less than 24 months of age (129) were seropositive,
      suggesting postnatal transmission of infection. Domestic cats were present on six
      of the eight farms. Three cats from one farm had MAT titers of 200. Viable T.
      gondii was isolated from the hearts of two cats, but not from brain tissues.
      Genotyping of isolate DNA extracted from culture-derived tachyzoites using 10 PCR
      restriction fragment length polymorphism (RFLP) markers (SAG1, SAG2, SAG3, BTUB,
      GRA6, c22-8, c29-2, PK1, L358 and Apico loci) revealed that both isolates were
      clonal Type II (ToxoDB PCR-RFLP genotype #1). This is the first serological
      survey for T. gondii in donkeys in the United States, and suggests that donkey
      milk and meat should be considered as a potential source for human infection. The
      role of barn cats in the transmission of T. gondii to donkeys on farms warrents
      further investigation.

PMID- 24140164
TI  - Self-medication with tannin-rich browse in goats infected with gastro-intestinal
      nematodes.
AB  - Primates self-medicate to alleviate symptoms caused by gastro-intestinal
      nematodes (GIN) by consuming plants that contain secondary compounds. Would goats
      display the same dietary acumen? Circumstantial evidence suggests they could:
      goats in Mediterranean rangelands containing a shrub - Pistacia lentiscus - with
      known anthelmintic properties consume significant amounts of the shrub,
      particularly in the fall when the probability of being infected with GIN is
      greatest, even though its tannins impair protein metabolism and deter herbivory.
      In order to test rigorously the self-medication hypothesis in goats, we conducted
      a controlled study using 21 GIN-infected and 23 non-infected goats exposed to
      browse foliage from P. lentiscus, another browse species - Phillyrea latifolia,
      or hay during the build-up of infection. GIN-infected goats showed clear symptoms
      of infection, which was alleviated by P. lentiscus foliage but ingesting P.
      lentiscus had a detrimental effect on protein metabolism in the absence of
      disease. When given a choice between P. lentiscus and hay, infected goats of the
      Mamber breed showed higher preference for P. lentiscus than non-infected
      counterparts, in particular if they had been exposed to Phillyrea latifolia
      before. This was not found in Damascus goats. Damascus goats, which exhibit
      higher propensity to consume P. lentiscus may use it as a drug prophylactically,
      whereas Mamber goats, which are more reluctant to ingest it, select P. lentiscus
      foliage therapeutically. These results hint at subtle trade-offs between the
      roles of P. lentiscus as a food, a toxin and a medicine. This is the first
      evidence of self-medication in goats under controlled conditions. Endorsing the
      concept of self-medication could greatly modify the current paradigm of
      veterinary parasitology whereby man decides when and how to treat GIN-infected
      animals, and result in transferring this decision to the animals themselves.

PMID- 24140165
TI  - The efficacy of avermectins (ivermectin, doramectin and abamectin) as treatments
      for infestation with the tick Haemaphysalis longicornis on rabbits in Korea.
AB  - The efficacy of a single subcutaneous injection of an avermectin (ivermectin,
      doramectin, or abamectin) as a treatment for infestation with nymphal and adult
      Haemaphysalis longicornis was evaluated in 24 New Zealand White rabbits. Two days
      after artificial infestation with nymphs or adult ticks, the rabbits were
      randomly allocated to three treatment groups (to be treated with ivermectin,
      doramectin, and abamectin) and a control group. The animals in the treatment
      groups were injected with commercial injectable formulations of each avermectins
      at a dose of 200 MUg/kg live weight. The results showed that on rabbits treated
      with these avermectins, nymphs and female ticks had significantly reduced weight,
      nymphs had reduced moulting success rates, and females had inhibited ovary
      development. Among the treatments, doramectin was most effective in reducing the
      weight of nymphs (weight was reduced by 80%) and females (by 97.3%); ivermectin
      was most effective in reducing the moulting success rate in nymphs (by 55%); and
      both doramectin and abamectin were effective in inhibiting the development of
      female ticks' ovaries (by 46%). Data from this investigation show that
      avermectins are suitable for the control of H. longicornis on rabbits in Korea.

PMID- 24140166
TI  - Melatonin suppresses markers of inflammation and oxidative damage in a human
      daytime endotoxemia model.
AB  - PURPOSE: Melatonin used as an exogenous drug has been documented to have potent
      antioxidant and anti-inflammatory effects in animal model. We aimed to examine
      the effect of melatonin in an experimental human sepsis model. MATERIALS AND
      METHODS: Twelve healthy males were enrolled in a randomized, placebo-controlled,
      double-blinded cross-over trial. They received lipopolysaccharide endotoxin 0.3
      ng/kg of body weight intravenously at 12:00. Before endotoxemia, an 8-hour
      infusion of melatonin (100 mg) or placebo (saline) was initiated. Blood samples
      were drawn before and at 2, 4, 6, and 8 hours after lipopolysaccharide
      administration. Proinflammatory (tumor necrosis factor alpha [TNF-alpha],
      interleukin [IL] 1beta, IL-6, and YKL-40), anti-inflammatory markers (IL-1Ra, IL
      10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor
      receptor II), a marker for oxidative damage (malondialdehyde), and antioxidants
      (ascorbic acid and dehydroascorbic acid) were analyzed in plasma. RESULTS:
      Melatonin significantly reduced proinflammatory markers IL-1beta (P < .01) and
      YKL-40 (P < .05) but not TNF-alpha and IL-6. None of the anti-inflammatory
      markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble
      tumor necrosis factor receptor II) were lowered by melatonin. Melatonin reduced
      the levels of ascorbic acid (P < .05) but not dehydroascorbic acid or
      malondialdehyde. CONCLUSIONS: Melatonin administration before endotoxemia
      resulted in reduction of certain markers of inflammation and oxidative stress.
      Further studies are needed to clarify the role of melatonin in clinical setting.

PMID- 24140167
TI  - Combat casualties undergoing lifesaving interventions have decreased heart rate
      complexity at multiple time scales.
AB  - PURPOSE: We found that heart rate (HR) complexity metrics such as sample entropy
      (SampEn) identified patients with trauma receiving lifesaving interventions
      (LSIs). We now aimed (1) to test a multiscale entropy (MSE) index, (2) to compare
      it to single-scale measures including SampEn, and (3) to assess different
      parameter values for calculation of SampEn and MSE. METHODS: This was a study of
      combat casualties in an emergency department in Iraq. Electrocardiograms of 70
      acutely injured adults were recorded. Twelve underwent LSIs and 58 did not.
      Lifesaving interventions included endotracheal intubation (9), tube thoracostomy
      (9), and emergency transfusion (4). From each electrocardiogram, a segment of 800
      consecutive beats was selected. Offline, R waves were detected and R-to-R
      interval time series were generated. Sample entropy, MSE, and time-domain
      measures of HR variability (mean HR, SD, the proportion of pairs of consecutive
      NN intervals that differ by more than 20 and 50 milliseconds, square root of the
      mean of the squares of differences between adjacent NN intervals) were computed.
      RESULTS: Differences in mean HR (LSI: 111 +/- 33, non-LSI: 90 +/- 17 beats/min)
      were not significant. Systolic arterial pressure was statistically but not
      clinically different (LSI: 123 +/- 19, non-LSI: 135 +/- 19 mm Hg). Sample entropy
      (LSI: 0.90 +/- 0.42, non-LSI: 1.19 +/- 0.35; P < .05) and MSE index (LSI: 2.58 +/
      2.55, non-LSI: 5.67 +/- 2.48; P < .001) differed significantly. CONCLUSIONS:
      Complexity of HR dynamics over a range of time scales was lower in high-risk than
      in low-risk combat casualties and outperformed traditional vital signs.

PMID- 24140168
TI  - The effect of positive balance on the outcomes of critically ill noncardiac
      postsurgical patients: a retrospective cohort study.
AB  - PURPOSE: Fluid balance remains a highly controversial topic in the critical care
      field, and no consensus has been reached about the fluid levels required by
      critically ill surgical patients. In this study, we investigated the relationship
      between fluid balance and in-hospital mortality in critically ill surgical
      patients. METHODS: The medical records of adult patients managed in a surgical
      intensive care unit (ICU) for more than 48 hours after surgery from January 2010
      to February 2011 were reviewed retrospectively. Abstracted data included body
      weights, Acute Physiology and Chronic Health Evaluation (APACHE) II scores,
      Sequential Organ Failure Assessment (SOFA) scores, fluid therapy values (intake,
      output, and balance) during the ICU stay, type of operation, length of stay in
      the ICU and hospital, and in-hospital mortality. RESULTS: A total of 148 patients
      were enrolled. The in-hospital mortality rate was 20.8%, and the median length of
      stay in the ICU and hospital were 5.0 and 24 days, respectively. The median daily
      fluid balance over the first 3 postoperative days was positive 11.2 mL/kg. Fluid
      balances in the ICU were 19.2, 15.0, and -0.6 mL kg(-1) d(-1), respectively,
      during the first 3 days vs SOFA scores (6.8, 6.3, and 6.5). Comparing the
      nonsurvival group with the survival group, the univariate analysis showed that
      age (P = .05), APACHE II score (P < .001), and use of a vasopressor
      (norepinephrine) (P = .05) affect in-hospital mortality. In the overall patients,
      any of the fluid balances were not significantly associated with mortality.
      However, in critically ill patients whose APACHE II scores were greater than 20,
      the nonsurvivor group showed a significant tendency toward a positive balance
      compared with the survivor group on the second and third days of ICU stay.
      Nevertheless, the SOFA scores showed no difference between nonsurvivor and
      survivors during the initial 2 postoperative days. CONCLUSION: In critically ill
      noncardiac postsurgical patients whose APAHCE II scores were greater than 20, a
      positive balance in the ICU can be associated with mortality risk. To determine
      the direct effect of positive fluid balance, a larger scaled, prospective
      randomized study will be required.

PMID- 24140169
TI  - Introducing depression and developmental screenings into the national programme
      on immunization (NPI) in southeast Nigeria: an experimental cross-sectional
      assessment.
AB  - OBJECTIVES: This study investigates the possibility of introducing depression and
      developmental screening tools into the National Programme on Immunization (NPI)
      in southeast Nigeria. The specific objectives were to determine the prevalence of
      postpartum depression (PPD) among mothers attending immunization clinics and to
      assess the association of maternal PPD and infant growth in relation to World
      Health Organization (WHO) recommendations. METHODS: Four hundred and eight (408)
      mothers completed the sociodemographic questionnaire and the self-report
      Edinburgh Postnatal Depression Scale (EPDS). The weights, lengths and head
      circumferences of their infants were recorded, while the WHO recommended
      equivalents at 50th percentiles were also recorded for each child. The mothers
      were then interviewed with the major depressive episode module of Mini
      International Neuropsychiatric Interview (M.I.N.I.) to make diagnosis of
      depression. RESULTS: About 24.8% and 15.2% of the mothers were found to be
      depressed using EPDS and major depressive episode module of M.I.N.I.,
      respectively. It was found that maternal PPD is significantly associated with the
      growth parameters of weights and lengths of the infants studied but not their
      head circumference. CONCLUSIONS: NPI may provide appropriate forum for early
      screening of mothers for PPD and interventions in Nigeria. The NPI would also
      serve a useful avenue of screening for developmental concerns in Nigerian
      children.

PMID- 24140170
TI  - Navigating the risk environment: structural vulnerability, sex, and reciprocity
      among women who use methamphetamine.
AB  - BACKGROUND: Drug users' risk sexual practices contribute to their increased risk
      for contracting HIV and other sexually transmitted infections. Use of
      methamphetamine has been associated with a number of high-risk sexual practices
      such as frequent sexual contacts, multiple sex partners, unprotected sex, and
      exchange sex. The media construct women who use methamphetamine as engaging in
      exchange sex to support their drug habit. Despite an abundance of data on
      exchange sex among heroin and crack users that suggest the importance of
      examining these practices in context, they remain understudied among female
      methamphetamine users. METHODS: This article draws on ongoing ethnographic
      research with female methamphetamine users. RESULTS: The research participants'
      risk environment(s) contribute to their structural vulnerability and shape
      behaviour in ways that are sometimes deemed transactional and risky by research,
      public health, or harm reduction professionals. CONCLUSION: Understanding the
      embeddedness of sexual practices in structural context and networks of
      reciprocity is essential to understanding implications for policy and harm
      reduction.

PMID- 24140171
TI  - Compulsory drug detention in East and Southeast Asia: response from the Global
      Fund to Fight AIDS, Tuberculosis and Malaria.

PMID- 24140172
TI  - Test-retest reliability of a 3-min isokinetic all-out test using two different
      cadences.
AB  - OBJECTIVES: To investigate the test-retest reliability of mechanical parameters
      derived from a 3-min isokinetic all-out test, performed at 60 and 100 rpm.
      Reliability and validity of the peak oxygen uptake derived from 3-min isokinetic
      all-out test were also tested. DESIGN: 14 healthy male subjects completed an
      incremental ramp testing and four randomized 3-min isokinetic all-out test (two
      at 60 rpm and two at 100 rpm). METHODS: The absolute and relative reliability of
      the following parameters were analyzed: peak power, mean power, end power,
      fatigue index, work performed above end power and peak oxygen uptake. RESULTS: No
      difference was found between each two sets of data, although there were between
      cadence differences for peak power, mean power, end power, and fatigue index.
      Higher intra-class correlation (ICC) and lower coefficient of variation (CV) were
      found for end power (ICC = 0.91 and 0.95; CV = 5.6 and 5.7%) and mean power (ICC
      = 0.97 and 0.98; CV = 2.4 and 3.1%), than for peak power (ICC = 0.81 and 0.84; CV
      = 8.7 and 10%) and work performed above end power (ICC = 0.79 and 0.84; CV = 7.9
      and 10.6%; values reported for 60 rpm and 100 rpm, respectively). High
      reliability scores were also observed for peak oxygen uptake at both cadences (60
      rpm, CV = 3.2%; 100 rpm, CV = 2.3%,) with no difference with the incremental ramp
      testing peak oxygen uptake. CONCLUSIONS: The power profile and peak oxygen uptake
      of a 3-min isokinetic all-out test are both highly reliable, whether the test is
      performed at 60 or 100 rpm. Besides, peak oxygen uptake and work performed above
      end power were not affected by the change in cadence while peak power, mean
      power, end power, and fatigue index were.

PMID- 24140173
TI  - Reference laboratory utilization management.
AB  - This chapter describes the unique challenges of managing reference laboratory
      utilization. The nature of reference laboratory testing and how it differs from
      routine hospital clinical laboratory testing is discussed. The vast majority of
      reference laboratory testing is high complexity, low volume testing to support
      specialized care. In contrast the hospital clinical laboratory is most effective
      at performing rapid turn-around, routine, high volume testing. The implication of
      these differences with respect to identifying utilization issues and
      interventions to manage utilization is presented along with examples. 

PMID- 24140174
TI  - Utilization management in anatomic pathology.
AB  - There is relatively little published literature concerning utilization management
      in anatomic pathology. Nonetheless there are many utilization management
      opportunities that currently exist and are well recognized. Some of these impact
      only the cost structure within the pathology department itself whereas others
      reduce charges for third party payers. Utilization management may result in
      medical legal liabilities for breaching the standard of care. For this reason it
      will be important for pathology professional societies to develop national
      utilization guidelines to assist individual practices in implementing a medically
      sound approach to utilization management. 

PMID- 24140175
TI  - [Evaluation of the impact of a hemodialysis center on environment and local
      ecology].
AB  - The prevalence of chronic kidney disease continues to increase worldwide,
      especially in our country with a consequent increase in patients requiring renal
      replacement therapy by hemodialysis, either temporarily or for life in the
      absence of a solid draft kidney transplant in the future. However, hemodialysis
      and peritoneal dialysis treatment are very expensive, very demanding in resources
      such as water and electricity and generate a large amount of waste. The objective
      of our work is to put the item in the environmental aspects of dialysis and its
      impact on the environment. This is a descriptive cross-sectional study conducted
      in the department of nephrology dialysis. Our hemodialysis center has 13
      generators with a private water treatment (mono osmosis). Our annual water
      consumption for a single hemodialysis generator for 10hours per day and 6days per
      week is estimated at 93.6m(3). The production volume of water discharged from the
      reverse osmosis system (concentrate rejected) is 12m(3)/day (66% of the volume of
      water treated by reverse osmosis) with physico-chemical and bacteriological
      parameters remaining in the standards of WHO/FAO irrigation potential. The living
      water treatment as well as our 13 generators need more than 156 KW/day for work.
      The waste generated is about 23.5 tons/year, classified as high risk because of
      the high rates of hepatitis C in our center (48%) and severity of bacterial flora
      that we have identified in the post-generator dialysate thrown directly into
      sewers. Our natural resources are valuable especially that we are among the world
      exposed to water shortages in the near future (Haut-Commissariat des eaux et
      forets et a la desertification du Maroc, 2009), which leads us to develop new
      programs to recycle waste and rejected in order to concentrate the reuse in
      various areas (irrigation, watering, sanitation, sterilization of surgical
      instruments), and to encourage the use of solar energy especially in a sunny
      country like ours. 

PMID- 24140176
TI  - Expression of MDR1 and MDR3 gene products in paclitaxel-, doxorubicin- and
      vincristine-resistant cell lines.
AB  - Multiple drug resistance is one of the main reasons for low chemotherapeutic
      efficiency in cancer patients. The proteins that are most frequently implicated
      to play a role in this mechanism are transmembrane proteins that are members of
      the ABC family. The most important ABC protein is MDR1 (ABCB1), which is
      expressed in over fifty percent of drug-resistant cancers. The
      phosphatidylcholine transporter, MDR3 (ABCB4), exhibits high homology with MDR1.
      An increasing body of evidence suggests that MDR3 plays a role in drug
      resistance. In the present study, we used doxorubicin-, paclitaxel- and
      vincristine-resistant cancer cell lines. A chemosensitivity assay MTT test was
      performed to assess drug resistance. Quantitative real-time polymerase chain
      reaction analyses were performed to determine the mRNA expression levels of the
      MDR1 and MDR3 genes. We observed dose-dependent responses to doxorubicin,
      paclitaxel and vincristine in the investigated cell lines. In all of the drug
      resistant cell lines that we studied, we observed increased MDR1 and MDR3
      transcript levels. In a doxorubicin-resistant variant of the LoVo cell line
      (LoVoDx), MDR3 was expressed at higher levels than MDR1. We also observed high
      correlations between MDR3 expression and resistance to doxorubicin and
      paclitaxel. Our results suggest that MDR3 plays an active and important role in
      drug resistance in the investigated cell lines. 

PMID- 24140177
TI  - 18:1/18:1-Dioleoyl-phosphatidylglycerol prevents alveolar epithelial apoptosis
      and profibrotic stimulus in a neonatal piglet model of acute respiratory distress
      syndrome.
AB  - BACKGROUND: 18:1/18:1-Dioleoyl-phosphatidylgycerol (DOPG) is a surfactant
      phospholipid that is nearly non-detectable in neonatal surfactant films. When
      alveolar macrophages are exposed to DOPG in vitro, secretory phospholipase A2
      (sPLA2) production is blocked, resulting in suppressed macrophage activity and
      improved surfactant function. We investigated whether the addition of DOPG to a
      commercially available surfactant preparation would improve lung function in a
      neonatal piglet model of acute respiratory distress syndrome. MATERIALS AND
      METHODS: Respiratory failure was achieved by triple-hit lung injury (repeated
      broncho-alveolar lavage, injurious ventilation, tracheal lipopolysaccharide
      instillation, each intervention 24 h apart) in twenty-four domestic piglets aged
      2-6 days and subject to mechanical ventilation. Following each lung injury
      protocol the piglets were treated with surfactant alone or with surfactant +
      DOPG. RESULTS: Within 72 h of mechanical ventilation, we observed significantly
      improved gas exchange (oxygenation and ventilation), lung mechanics (compliance
      and resistance of the respiratory system), and pulmonary oedema (extra-vascular
      lung water index) in the surfactant + DOPG group. This favourable clinical effect
      could be attributed to improved surfactant function, reduced sPLA2 secretion,
      inhibition of macrophage migration, reduced alveolar epithelial apoptosis, and
      suppression of amphiregulin and TGF-beta1 expression in pulmonary tissues as a
      prerequisite for fibrous lung repair. CONCLUSIONS: We conclude that surfactant
      fortified by DOPG preserves lung function, and prevents alveolar epithelial
      injury and fibrous stimulus by reduction of sPLA2 in a neonatal model of acute
      respiratory distress syndrome without any relevant discernable side effects.
      Hence, DOPG supplementation in a neonatal lung exerts important function
      protecting effects and seems to be justified in cases of overwhelming pulmonary
      inflammation.

PMID- 24140178
TI  - Rational design of gold nanoparticles functionalized with carboranes for
      application in Boron Neutron Capture Therapy.
AB  - In this paper we propose a bottom-up approach to obtain new boron carriers built
      with ortho-carborane functionalized gold nanoparticles (GNPs) for applications in
      Boron Neutron Capture Therapy. The interaction between carboranes and the gold
      surface was assured by one or two SH-groups directly linked to the boron atoms of
      the B10C2 cage. This allowed obtaining stable, nontoxic systems, though optimal
      biological performance was hampered by low solubility in aqueous media. To
      improve cell uptake, the hydrophilic character of carborane functionalized GNPs
      was enhanced by further coverage with an appropriately tailored diblock copolymer
      (PEO-b-PCL). This polymer also contained pendant carboranes to provide anchoring
      to the pre-functionalized GNPs. In vitro tests, carried out on osteosarcoma
      cells, showed that the final vectors possessed excellent biocompatibility joint
      to the capacity of concentrating boron atoms in the target, which is encouraging
      evidenced to pursue applications in vivo. 

PMID- 24140179
TI  - Insertion of distal locking screws of tibial intramedullary nails: a comparison
      between the free-hand technique and the SURESHOTTM Distal Targeting System.
AB  - INTRODUCTION: Positioning of the distal locking screws of an intramedullary nail
      is often challenging and time consuming because of difficult localisation of the
      distal locking holes, potential screw malalignment and nail deformation during
      insertion. The standard free-hand technique under fluoroscopic control involves
      considerable radiation exposure of both the patient and the surgical team. In
      this study, we aimed to compare the free-hand technique with a new system that
      utilises electromagnetic (EM) tracking data (SURESHOTTM Distal Targeting System)
      to localise distal locking holes. MATERIAL AND METHODS: Patients admitted from
      March 2010 to January 2013 for tibial fracture that required intramedullary
      nailing were analysed retrospectively. We compared intraoperative radiation
      exposure time and distal locking time in patients treated with the standard free
      hand technique and distal locking using the EM field-generating device.
      Intraoperative radiation exposure time and distal locking time were used for
      comparison. RESULTS: Data from a total of 50 patients were analysed. The standard
      free-hand technique and the EM field-generating device were used in 25 (group 1)
      and 25 (group 2) patients, respectively. Mean distal locking time was 1258.6 (450
      2289) s in group 1 and 603.5 (360-1140)s in group 2. Mean radiation exposure time
      was 19.4 (6-33) s in group 1 and 4.6 (1-10) s in group 2. CONCLUSION: The EM
      field-generating device significantly reduces distal locking time and, more
      importantly, significantly decreases duration of exposure to ionising radiation.

PMID- 24140180
TI  - The association between content of the elements S, Cl, K, Fe, Cu, Zn and Br in
      normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by
      dual hierarchical clustering analysis.
AB  - PROJECT: Meta-analysis of previous studies evaluating associations between
      content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper
      (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue
      samples. PROCEDURE: Normal liver samples from 45 Greenlandic Inuit, median age 60
      years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27
      Danes, median age 71 years. Element content was measured using X-ray fluorescence
      spectrometry. STATISTICS: Dual hierarchical clustering analysis, creating a dual
      dendrogram, one clustering element contents according to calculated similarities,
      one clustering elements according to correlation coefficients between the element
      contents, both using Euclidian distance and Ward Procedure. RESULTS: One
      dendrogram separated subjects in 7 clusters showing no differences in ethnicity,
      gender or age. The analysis discriminated between elements in normal and
      cirrhotic livers. The other dendrogram clustered elements in four clusters:
      sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were
      significant correlations between the elements in normal liver samples: S was
      associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with
      Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant
      associations with any other element. CONCLUSIONS: In contrast to simple
      statistical methods, which analyses content of elements separately one by one,
      dual hierarchical clustering analysis incorporates all elements at the same time
      and can be used to examine the linkage and interplay between multiple elements in
      tissue samples.

PMID- 24140181
TI  - [The pulmonary-renal syndrome: a diagnostic and therapeutic emergency for the
      internist and the intensivist].
AB  - The pulmonary-renal syndrome is a rare and life-threatening condition. It is
      defined as the association of a diffuse alveolar hemorrhage and a rapidly
      progressive glomerulonephritis. The characteristic histological lesion common to
      all underlying diseases is a necrotizing and crescentic glomerulonephritis. The
      pulmonary-renal syndrome is a diagnostic and therapeutic emergency: any delay in
      its management will lead to death or serious functional damage as pulmonary and
      renal impairment. ANCA-associated vasculitis and Goodpasture's disease are the
      main disorders associated to pulmonary-renal syndrome. More rarely systemic
      lupus, cryoglobulinaemia, Henoch-Schonlein purpura or subacute endocarditis may
      induce a pulmonary-renal syndrome. Differential diagnosis can sometimes be
      difficult, highlighting some ambiguity in the definition of the syndrome. Initial
      treatment usually associates systemic corticosteroid, cyclophosphamide and plasma
      exchange. The role of biotherapy as first line therapy remains to be determined. 

PMID- 24140182
TI  - Axitinib dose titration: what's the limiting factor?

PMID- 24140183
TI  - Resumption of imatinib to control metastatic or unresectable gastrointestinal
      stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised,
      placebo-controlled, phase 3 trial.
AB  - BACKGROUND: Few treatment options remain for patients with metastatic or
      unresectable gastrointestinal stromal tumours (GIST) after objective progression
      on approved tyrosine-kinase inhibitors. We aimed to assess efficacy of imatinib
      rechallenge in these patients. METHODS: In our prospective, randomised, double
      blind trial, we enrolled adults (>=18 years) who had previously benefited from
      first-line imatinib (initial response or stable disease for >=6 months) but whose
      metastatic or unresectable GIST had progressed on at least imatinib and
      sunitinib. We randomly allocated participants in a 1:1 ratio, with a centralised
      computer-generated allocation procedure (random permuted blocks of two, four, and
      six) and stratified by previous treatment and Eastern Cooperative Oncology Group
      performance status, to receive best supportive care with imatinib 400 mg per day
      or matched placebo. Crossover to open-label imatinib was allowed after
      investigator-adjudicated disease progression. The primary endpoint was
      progression-free survival (PFS), as determined by a masked external radiological
      review. All analyses were done for all patients who received at least one dose of
      study drug. FINDINGS: Between July 20, 2010, and Jan 17, 2013, we randomly
      allocated 41 patients to the imatinib group and 40 patients to the placebo group.
      After a median follow-up of 5.2 months (IQR 3.4-9.4), median PFS was 1.8 months
      (95% CI 1.7-3.6) with imatinib compared with 0.9 months (0.9-1.7) with placebo
      (hazard ratio for progression or death 0.46, 95% CI 0.27-0.78; p=0.005). 37 (93%)
      patients in the placebo group crossed over to open-label imatinib after
      progression. The most common grade 3 or worse adverse events were anaemia (12
      [29%] of 41 patients in the imatinib group vs three [8%] of 40 in the placebo
      group), fatigue (four [10%] vs none), and hyperbilirubinaemia (three [7%] vs one
      [3%]). INTERPRETATION: In patients with GIST that is refractory to treatment with
      all standard tyrosine-kinase inhibitors, the disease continues to harbour many
      clones that are sensitive to kinase inhibitors. Continued kinase suppression
      might slow, although not halt, disease progression.

PMID- 24140185
TI  - Rechallenge of drugs in the era of targeted therapy.

PMID- 24140184
TI  - Axitinib with or without dose titration for first-line metastatic renal-cell
      carcinoma: a randomised double-blind phase 2 trial.
AB  - BACKGROUND: Population pharmacokinetic data suggest axitinib plasma exposure
      correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose
      titration might optimise exposure and improve outcomes. We prospectively assessed
      the efficacy and safety of axitinib dose titration in previously untreated
      patients with metastatic renal-cell carcinoma. METHODS: In this randomised,
      double-blind, multicentre, phase 2 study, patients were enrolled from 49
      hospitals and outpatient clinics in the Czech Republic, Germany, Japan, Russia,
      Spain, and USA. Patients with treatment-naive metastatic renal-cell carcinoma
      received axitinib 5 mg twice daily during a 4 week lead-in period. Those patients
      with blood pressure 150/90 mm Hg or lower, no grade 3 or 4 treatment-related
      toxic effects, no dose reductions, and no more than two antihypertensive drugs
      for 2 consecutive weeks were stratified by Eastern Cooperative Oncology Group
      performance status (0 vs 1), and then randomly assigned (1:1) to either masked
      titration with axitinib to total twice daily doses of 7 mg, and then 10 mg, if
      tolerated, or placebo titration. Patients who did not meet these criteria
      continued without titration. The primary objective was comparison of the
      proportion of patients achieving an objective response between randomised groups.
      Safety analyses were based on all patients who received at least one dose of
      axitinib. FINDINGS: Between Sept 2, 2009, and Feb 28, 2011, we enrolled 213
      patients, of whom 112 were randomly assigned to either the axitinib titration
      group (56 patients) or the placebo titration group (56 patients). 91 were not
      eligible for titration, and ten withdrew during the lead-in period. 30 patients
      (54%, 95% CI 40-67) in the axitinib titration group had an objective response, as
      did 19 patients (34%, 22-48]) in the placebo titration group (one-sided p=0.019).
      54 (59%, 95% CI 49-70) of non-randomised patients achieved an objective response.
      Common grade 3 or worse, all-causality adverse events in treated patients were
      hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56
      in the placebo titration group vs 45 [49%] of 91 in the non-randomised group),
      diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four
      [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events
      were reported in 15 (27%) patients in the axitinib titration group, 13 (23%)
      patients in the placebo titration group, and 35 (38%) non-randomised patients.
      The most common serious adverse events in all 213 patients were disease
      progression and dehydration (eight each [4%]), and diarrhoea, vomiting,
      pneumonia, and decreased appetite (four each [2%]). INTERPRETATION: The greater
      proportion of patients in the axitinib titration group achieving an objective
      response supports the concept of individual axitinib dose titration in selected
      patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity
      with a manageable safety profile in treatment-naive patients with this disease.

PMID- 24140186
TI  - High expression of small hepatitis D antigen in Escherichia coli and ELISA for
      diagnosis of hepatitis D virus.
AB  - Hepatitis D virus (HDV) infection is often accompanied by hepatitis B virus (HBV)
      infection. Co-infection of HDV and HBV may lead to more severe symptoms and even
      death. Current methods for HDV diagnosis have high false-positive rates and show
      significant result discrepancies. The Abbott AxSYM AUSAB test, currently a
      standard test for HDV detection, is too laborious and expensive for routine
      application. Therefore, new sensitive and cost-efficient methods for HDV
      diagnosis are urgently needed. In this study, S-HDAg protein was produced in high
      yield in Escherichia coli. Optimal protein production was achieved by
      optimization of S-HDAg gene codons according to the codon preference of E. coli
      and using host cells with appropriate cell density. Under optimal expression
      conditions, the S-HDAg protein expression yield (30mg/l) was the highest among
      any proteins expressed in E. coli. A standard enzyme-linked immunosorbent assay
      (ELISA) for HDV was developed using the purified S-HDAg protein, which showed
      high specificity against hepatitis B, C, D and E viruses. Overall, the ELISA had
      superior specificity and sensitivity compared with the Abbott AxSYM AUSAB test
      and was also more convenient and cost-efficient. 

PMID- 24140187
TI  - Establishment of tracking system for West Nile virus entry and evidence of
      microtubule involvement in particle transport.
AB  - West Nile virus (WNV) is one of flaviviruses and has emerged recently in the
      United States as a significant cause of viral encephalitis. Although cellular
      entry of WNV is important for viral pathogenesis, its mechanisms have not been
      elucidated fully. To explore the entry mechanisms, a virus-particle tracking
      system in live cells by using fluorescently labeled subviral particles (SVPs) and
      time-lapse epifluorescence microscopy was established. This study revealed that,
      following cellular entry, SVP movements could be divided into two phases: early
      (slow movement) and late (fast movement) phase. Moreover, fast viral particle
      movements at the late phase correlated with SVP-microtubule association. 

PMID- 24140188
TI  - Psychotropic-induced hyperprolactinemia: a clinical review.
AB  - BACKGROUND: Psychotropic medications, particularly select antipsychotics, are a
      common cause of drug-induced hyperprolactinemia. As high prolactin may be
      associated with hypogonadism, reproductive dysfunction, and bone loss, it is
      important to recognize this condition and understand its management. OBJECTIVE:
      The aim of this review is to evaluate the causes, signs, and symptoms associated
      with hyperprolactinemia, to describe mechanisms through which psychotropic
      medications elevate prolactin, and to suggest an evidence-based management
      approach for patients with psychotropic drug-induced hyperprolactinemia. METHODS:
      A PubMed/MEDLINE search was conducted on the topic of psychotropic agents as a
      cause of hyperprolactinemia. The material with most relevance to current
      psychiatric practice and of highest level of evidence was included in this
      review. CONCLUSION: Hyperprolactinemia should be evaluated in adult patients
      receiving psychotropic agents if signs and symptoms associated with
      hyperprolactinemia are present. It is also important to exclude pituitary and
      hypothalamic disease by magnetic resonance imaging if hyperprolactinemia is not
      definitely caused by psychotropic medications. As bone loss may occur because of
      hyperprolactinemia-mediated hypogonadism, bone mineral density (BMD) should be
      evaluated in patients with persistent high prolactin and reproductive
      dysfunction. Aripiprazole or other prolactin-sparing atypical antipsychotics may
      be alternatives or aripiprazole can be considered as adjunctive therapy in select
      cases of psychotropic-induced hyperprolactinemia.

PMID- 24140189
TI  - Beta-catenin patterns the cell cycle during maternal-to-zygotic transition in
      urochordate embryos.
AB  - During the transition from maternal to zygotic control of development, cell cycle
      length varies in different lineages, and this is important for their fates and
      functions. The maternal to zygotic transition (MZT) in metazoan embryos involves
      a profound remodeling of the cell cycle: S phase length increases then G2 is
      introduced. Although beta-catenin is the master regulator of endomesoderm
      patterning at MZT in all metazoans, the influence of maternal beta-catenin on the
      cell cycle at MZT remains poorly understood. By studying urochordate
      embryogenesis we found that cell cycle remodeling during MZT begins with the
      formation of 3 mitotic domains at the 16-cell stage arising from differential S
      phase lengthening, when endomesoderm is specified. Then, at the 64-cell stage, a
      G2 phase is introduced in the endoderm lineage during its specification.
      Strikingly, these two phases of cell cycle remodeling are patterned by beta
      catenin-dependent transcription. Functional analysis revealed that, at the 16
      cell stage, beta-catenin speeds up S phase in the endomesoderm. In contrast, two
      cell cycles later at gastrulation, nuclear beta-catenin induces endoderm fate and
      delays cell division. Such interphase lengthening in invaginating cells is known
      to be a requisite for gastrulation movements. Therefore, in basal chordates beta
      catenin has a dual role to specify germ layers and remodel the cell cycle. 

PMID- 24140190
TI  - Into a stand of aspen.

PMID- 24140191
TI  - Wilderness Medical Society practice guidelines for the prevention and treatment
      of heat-related illness.
AB  - The Wilderness Medical Society (WMS) convened an expert panel to develop a set of
      evidence-based guidelines for the recognition, prevention, and treatment of heat
      related illness. We present a review of the classifications, pathophysiology, and
      evidence-based guidelines for planning and preventive measures as well as best
      practice recommendations for both field- and hospital-based therapeutic
      management of heat-related illness. These recommendations are graded based on the
      quality of supporting evidence and the balance between the benefits and risks or
      burdens for each modality. 

PMID- 24140193
TI  - [High flow therapy in wards. An alternative to admission to Pediatric Intensive
      Care Unit?].

PMID- 24140194
TI  - Sulfur recirculation for increased electricity production in Waste-to-Energy
      plants.
AB  - Sulfur recirculation is a new technology for reducing boiler corrosion and dioxin
      formation. It was demonstrated in full-scale tests at a Waste to Energy plant in
      Goteborg (Sweden) during nearly two months of operation. Sulfur was recirculated
      as sulfuric acid from the flue gas cleaning back to the boiler, thus creating a
      sulfur loop. The new technology was evaluated by extensive measurement campaigns
      during operation under normal conditions (reference case) and operation with
      sulfur recirculation. The chlorine content of both fly ash and boiler ash
      decreased and the sulfur content increased during the sulfur recirculation tests.
      The deposit growth and the particle concentration decreased with sulfur
      recirculation and the dioxin concentration (I-TEQ) of the flue gas was reduced by
      approximately 25%. Sulfuric acid dew point measurements showed that the sulfuric
      acid dosage did not lead to elevated SO3 concentrations, which may otherwise
      induce low temperature corrosion. In the sulfur recirculation corrosion probe
      exposures, the corrosion rate decreased for all tested materials (16Mo3, Sanicro
      28 and Inconel 625) and material temperatures (450  degrees C and 525  degrees C)
      compared to the reference exposure. The corrosion rates were reduced by 60-90%.
      Sulfur recirculation prevented the formation of transition metal chlorides at the
      metal/oxide interface, formation of chromate and reduced the presence of zinc in
      the corrosion products. Furthermore, measured corrosion rates at 525  degrees C
      with sulfur recirculation in operation were similar or lower compared to those
      measured at 450  degrees C material temperature in reference conditions, which
      corresponds to normal operation at normal steam temperatures. This implies that
      sulfur recirculation allows for higher steam data and electricity production
      without increasing corrosion.

PMID- 24140195
TI  - [Prognosis assessment of alcoholic liver disease: how and why?].
AB  - Alcoholic liver disease (ALD) causes more than 5000 deaths per year in France.
      Most of those deaths could be prevented by an early diagnosis, which would give
      the patients the opportunity to modify their alcohol consumption while liver
      lesions are still reversible. Hepatic histology is the main parameter that
      predicts morbidity and mortality in patients with ALD. Non-invasive methods such
      as biomarker tests (e.g. FibroTest((r)) or FibroMetre A((r))) or hepatic
      elastography (FibroScan((r))) may allow diagnosing alcohol-induced liver lesion
      without systematic biopsy. Despite promising preliminary results, those methods
      are not validated yet in ALD. A validation of non-invasive methods for ALD could
      allow a large screening of the severe forms of this pathology.

PMID- 24140196
TI  - Bilateral femtosecond laser-enabled intrastromal astigmatic keratotomy to correct
      high post-penetrating keratoplasty astigmatism.
AB  - A 35-year-old man presented with bilateral high astigmatism following penetrating
      keratoplasties performed for advanced keratoconus. Femtosecond laser-enabled
      intrastromal astigmatic keratotomy was performed, resulting in a significant
      reduction in corneal astigmatism. At 4 months, the corneal astigmatism continued
      to decrease. The visual acuity, refraction, and serial corneal topographic data
      are presented.

PMID- 24140197
TI  - Preoperative anterior segment optical coherence tomography as a predictor of
      postoperative phakic intraocular lens position.
AB  - PURPOSE: To evaluate anterior segment optical coherence tomography (AS-OCT) in
      the preoperative simulation of postoperative iris-fixated phakic intraocular lens
      (pIOL) position in the anterior chamber. SETTING: Farabi Eye Research Center,
      Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran.
      DESIGN: Case series. METHODS: Using AS-OCT, the pIOL position was simulated
      preoperatively in 2 ways and compared with the actual postoperative pIOL
      position. For preoperative evaluations, the simulator was placed on the posterior
      pigmented epithelium of the iris. Then, the simulation was performed with the
      simulator placed in the middle of the iris tissue. The following distances were
      measured: from the center of the pIOL to the endothelium, from the edge of the
      pIOL to the endothelium, and from the posterior surface of the pIOL to the
      crystalline lens. RESULTS: The study examined 26 eyes (16 patients). Although all
      distances in both simulation methods (except the lens vault in the first method
      of simulation) were highly correlated (all P<.009), only the results with the
      simulator placed in the middle of the iris tissue were not statistically
      different from the corresponding postoperative measurements (P=.209 and P=.564
      for distance from endothelium to the center and the pIOL edge, respectively).
      CONCLUSIONS: Using the pIOL template of the AS-OCT system for preoperative
      simulation of iris-fixated pIOLs improved the criteria for patient selection for
      implantation of these pIOLs. The simulator should be placed in the middle of the
      iris tissue for preoperative simulation. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 24140198
TI  - Inferior ectopic bone formation of mesenchymal stromal cells from adipose tissue
      compared to bone marrow: rescue by chondrogenic pre-induction.
AB  - Human mesenchymal stromal cells derived from bone marrow (BMSC) and adipose
      tissue (ATSC) represent a valuable source of progenitor cells for cell therapy
      and tissue engineering. While ectopic bone formation is a standard activity of
      human BMSC on calcium phosphate ceramics, the bone formation capacity of human
      ATSC has so far been unclear. The objectives of this study were to assess the
      therapeutic potency of ATSC for bone formation in an ectopic mouse model and
      determine molecular differences by standardized comparison with BMSC. Although
      ATSC contained less CD146(+) cells, exhibited better proliferation and displayed
      similar alkaline phosphatase activity upon osteogenic in vitro differentiation,
      cells did not develop into bone-depositing osteoblasts on beta-TCP after 8weeks
      in vivo. Additionally, ATSC expressed less BMP-2, BMP-4, VEGF, angiopoietin and
      IL-6 and more adiponectin mRNA, altogether suggesting insufficient osteochondral
      commitment and reduced proangiogenic activity. Chondrogenic pre-induction of
      ATSC/beta-TCP constructs with TGF-beta and BMP-6 initiated ectopic bone formation
      in >75% of samples. Both chondrogenic pre-induction and the osteoconductive
      microenvironment of beta-TCP were necessary for ectopic bone formation by ATSC
      pointing towards a need for inductive conditions/biomaterials to make this more
      easily accessible cell source attractive for future applications in bone
      regeneration. 

PMID- 24140200
TI  - Untangling BRCA mutations, sex hormones, and cancer risk.

PMID- 24140201
TI  - US shutdown: not all services are "non-essential".

PMID- 24140199
TI  - Recurrence patterns across medulloblastoma subgroups: an integrated clinical and
      molecular analysis.
AB  - BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is
      almost always fatal. Studies have confirmed that medulloblastoma consists of at
      least four distinct subgroups. We sought to delineate subgroup-specific
      differences in medulloblastoma recurrence patterns. METHODS: We retrospectively
      identified a discovery cohort of all recurrent medulloblastomas at the Hospital
      for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and
      established molecular subgroups using a nanoString-based assay on formalin-fixed
      paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence
      (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival
      after recurrence were assessed in a subgroup-specific manner. Two independent,
      non-overlapping cohorts (cohort 2: samples from patients with recurrent
      medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012;
      cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN
      Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were
      analysed to confirm and validate observations. When possible, molecular
      subgrouping was done on tissue obtained from both the initial surgery and at
      recurrence. RESULTS: Cohort 1 consisted of 30 patients with recurrent
      medulloblastomas; nine with local recurrences, and 21 with metastatic
      recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with
      recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in
      all 34 cases with available matched primary and recurrent pairs (five pairs from
      cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This
      finding was validated in 17 pairs from cohort 3. When analysed in a subgroup
      specific manner, local recurrences in cohort 1 were more frequent in SHH tumours
      (eight of nine [89%]) and metastatic recurrences were more common in group 3 and
      group 4 tumours (17 of 20 [85%] with one WNT, p=0.0014, local vs metastatic
      recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of
      recurrence was confirmed in cohort 2 (p=0.0013 for local vs metastatic
      recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0.0001). Treatment with
      craniospinal irradiation at diagnosis was not significantly associated with the
      anatomical pattern of recurrence. Survival after recurrence was significantly
      longer in patients with group 4 tumours in cohort 1 (p=0.013) than with other
      subgroups, which was confirmed in cohort 2 (p=0.0075), but not cohort 3 (p=0.70).
      INTERPRETATION: Medulloblastoma does not change subgroup at the time of
      recurrence, reinforcing the stability of the four main medulloblastoma subgroups.
      Significant differences in the location and timing of recurrence across
      medulloblastoma subgroups have potential treatment ramifications. Specifically,
      intensified local (posterior fossa) therapy should be tested in the initial
      treatment of patients with SHH tumours. Refinement of therapy for patients with
      group 3 or group 4 tumours should focus on metastases.

PMID- 24140202
TI  - Genetics of recurrent medulloblastoma.

PMID- 24140203
TI  - The sex hormone system in carriers of BRCA1/2 mutations: a case-control study.
AB  - BACKGROUND: Penetrance for breast cancer, ovarian cancer, or both in carriers of
      BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and
      altered end-organ hormone sensitivity might explain this organ-specific
      penetrance. We sought to identify differences in hormone regulation between
      carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations. METHODS: We
      assessed endometrial thickness for each menstrual cycle day (as an index of
      hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer
      Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754
      women known to be negative for the mutations. To quantify differences in
      endometrial thickness we focused on days 10-14 and days 21-26, and calculated the
      area under the curve. We then compared serum oestradiol and progesterone titres
      during these days of the menstrual cycle in the same groups. Follicular and
      luteal oestradiol and progesterone serum titres were grouped into quartiles and
      odds ratios were calculated with logistic regression. FINDINGS: Follicular phase
      endometrial thickness of carriers of the mutations adjusted for age and day of
      the menstrual cycle was higher (odds ratio [OR] 1.11, 95% CI 1.03-1.20; p=0.0063)
      and luteal phase endometrial thickness lower (0.90, 0.83-0.98; p=0.027) than for
      women negative for the mutations. Median luteal phase titres of progesterone were
      121% higher (p=0.00037) in carriers than in women negative for the mutations, and
      for oestradiol were 33% higher (p=0.007)-ie, 59% of carriers had concentrations
      of serum progesterone that would have been in the top quartile of concentrations
      in the control group (OR 8.0, 95% CI 2.1-52.57; p=0.008). INTERPRETATION:
      Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and
      progesterone-known risk-factors for breast cancer. Higher titres of oestradiol in
      carriers are compatible with this hormone having a role in ovarian carcinogenesis
      in such women. Our findings could not be explained by differential contraceptive
      pill use.

PMID- 24140204
TI  - Evaluation of the antinociceptive and anti-inflammatory effect of Caralluma
      dalzielii.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma dalzielii has been used for treating
      several ailments including convulsion, leprosy, snake bites, otitis (ear pain),
      fungal diseases and rheumatoid arthritis in Northern Nigeria. However there is no
      scientific evidence to support its use in literature. To evaluate the
      antinociceptive and anti-inflammatory properties of the aqueous extract of
      Caralluma dalzielii in animal models. MATERIALS AND METHODS: The antinociceptive
      and anti-inflammatory properties were assessed using acetic acid induced writhing
      test in mice, sub plantar formalin induced nociception, the tail-flick test and
      formalin induced oedema in rats. Three doses of the extract (25, 50, 100 mg/kg)
      were used for the assessment. RESULTS: Caralluma dalzielii extract demonstrated
      strong dose-dependent antinociceptive and anti-inflammatory activities in all the
      models employed. All doses (25, 50, 100 mg/kg) produced a significant percentage
      inhibition (41.77, 77.11, and 90.76% in the early phase and 52.02, 85.35, 93.93%
      in the late phase) in the acetic acid writhing test and (42.85, 55.71, 86.43% in
      the early phase and 23.26, 37.98, 72.87 in the late phase) in the formalin
      induced nociception test, respectively. The tail-flick test showed a significant
      increase in the antinociceptive effect of the extract in both early and late
      phases when compared with the control. The inhibition of oedema in the formalin
      test was significant when compared to the control. CONCLUSION: The results
      indicated that Caralluma dalzielii showed excellent antinociceptive and anti
      inflammatory properties suggesting that its traditional use in the treatment of
      pains and inflammatory diseases may be valid.

PMID- 24140205
TI  - The molecular dissection of the chaperone-usher pathway.
AB  - Secretion systems are specialized in transport of proteins, DNA or nutrients
      across the cell envelope of bacteria and enable them to communicate with their
      environment. The chaperone-usher (CU) pathway is used for assembly and secretion
      of a large family of long adhesive protein polymers, termed pili, and is
      widespread among Gram-negative pathogens [1]. Moreover, recent evidence has
      indicated that CU secretion systems are also involved in sporulation [2,3]. In
      this review we focus on the structural biology of the paradigmatic type 1 and P
      pili CU systems encoded by uropathogenic Escherichia coli (UPEC), where recent
      progress has provided unprecedented insights into pilus assembly and secretion
      mechanism. This article is part of a Special Issue entitled: Protein trafficking
      and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. 

PMID- 24140206
TI  - Progesterone regulates the expression and activity of two mouse isoforms of the
      glycoprotein folding sensor UDP-Glc: glycoprotein glucosyltransferase (UGGT).
AB  - UDP-Glucose:glycoprotein glucosyltransferase (UGGT) is a central component of the
      endoplasmic reticulum (ER) glycoprotein-folding quality control system, which
      prevents the exit of partially folded species. UGGT activity can be regulated by
      the accumulation of misfolded proteins in the ER, a stimulus that triggers a
      complex signaling pathway known as unfolded protein response (UPR) which is
      closely associated with inflammation and disease. In this work, we investigated
      the effect of progesterone (P4) on the expression and activity of UGGT in a mouse
      hybridoma. We detected the expression of two UGGT isoforms, UGGT1 and UGGT2, and
      demonstrated that both isoforms are active in these cells. Interestingly, the
      expression of each isoform is regulated by high physiological P4 concentrations.
      This work provides the first evidence of a hormonal regulation of UGGT isoform
      expression and activity, which might influence the glycoprotein quality control
      mechanism. These findings could contribute to the study of pathologies triggered
      by the accumulation of misfolded proteins. 

PMID- 24140207
TI  - BAG3 is upregulated by c-Jun and stabilizes JunD.
AB  - BAG3 plays a regulatory role in a number of cellular processes, including cell
      proliferation, apoptosis, adhesion and migration, epithelial-mesenchymal
      transition (EMT), autophagy activation, and virus infection. The AP-1
      transcription factors are implicated in a variety of important biological
      processes including cell differentiation, proliferation, apoptosis and
      oncogenesis. Recently, it has been reported that AP-1 protein c-Jun inhibits
      autophagy and enhances apoptotic cell death mediated by starvation. However, the
      molecular mechanisms remain unclear. For the first time, the current study
      demonstrated that serum starvation downregulated BAG3 at the transcriptional
      level via c-Jun. In addition, the current study reported that BAG3 stabilized
      JunD mRNA, which was, at least in part, responsible for the promotion of serum
      starvation mediated-growth inhibition by BAG3. 

PMID- 24140208
TI  - The Tat system of Gram-positive bacteria.
AB  - The twin-arginine protein translocation (Tat) system has a unique ability to
      translocate folded and co-factor-containing proteins across lipid bilayers. The
      Tat pathway is present in bacteria, archaea and in the thylakoid membranes of
      chloroplasts and, depending on the organism and environmental conditions, it can
      be deemed important for cell survival, virulence or bioproduction. This review
      provides an overview of the current understanding of the Tat system with specific
      focus on Gram-positive bacteria. The 'universal minimal Tat system' is composed
      of a TatA and a TatC protein. However, this pathway is more commonly composed of
      two TatA-like proteins and one TatC protein. Often the TatA-like proteins have
      diverged to have two different functions and, in this case, the second TatA-like
      protein is usually referred to as TatB. The correct folding and/or incorporation
      of co-factors are requirements for translocation, and the known quality control
      mechanisms are examined in this review. A number of examples of crosstalk between
      the Tat system and other protein transport systems, such as the Sec-YidC
      translocon and signal peptidases or sheddases are also discussed. Further, an
      overview of specific Gram-positive bacterial Tat systems found in monoderm and
      diderm species is detailed. Altogether, this review highlights the unique
      features of Gram-positive bacterial Tat systems and pinpoints key questions that
      remain to be addressed in future research. This article is part of a Special
      Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors:
      Anastassios Economou and Ross Dalbey. 

PMID- 24140209
TI  - Long-term clinical outcomes 15 years after aortic valve replacement with the
      Freestyle stentless aortic bioprosthesis.
AB  - BACKGROUND: The Freestyle stentless aortic root bioprosthesis has excellent
      hemodynamics and durability through 10 years. The purpose of this report is to
      present clinical outcomes in a large multicenter cohort through 15 years.
      METHODS: The multicenter evaluation of the Freestyle valve began in 1992 at 21
      centers in North America and Europe. In 1997, a long-term study continued,
      including 725 patients from 8 of the original centers; clinical outcomes data
      after 10 years have continued to be collected at 6 of 8 centers. RESULTS: Patient
      age was 71.7+/-7.9 years. There were 402 (55.4%) men and 323 (44.6%) women. Total
      follow-up was 5,491.2 patient-years. There were 52 late reoperations, with
      explant of the bioprosthesis in 47 cases. Respective 10- and 15-year survival was
      46.2%+/-2.3% and 25.9%+/-3.2%; freedom from valve-related death was 94.9%+/-1.5%
      and 92.7%+/-3.5%; freedom from reoperation was 92.3%+/-1.8% and 80.7%+/-5.0%; and
      freedom from explant owing to structural valve deterioration was 96.5%+/-1.3% and
      83.3%+/-4.8%. Increased age was associated with higher risks of all-cause
      mortality and valve-related mortality and lower risks of reoperation and explant
      caused by structural valve deterioration. CONCLUSIONS: In this long-term,
      multicenter, observational study, the Freestyle stentless aortic root
      bioprosthesis offered good clinical outcomes in terms of survival, freedom from
      valve-related mortality, freedom from reoperation, and freedom from structural
      valve deterioration. The Freestyle valve is a viable option for use in patients
      undergoing bioprosthetic aortic valve replacement and for anticipated desire for
      long-term durability.

PMID- 24140210
TI  - Clinical results of transcatheter aortic valve implantation in octogenarians and
      nonagenarians: insights from the FRANCE-2 registry.
AB  - BACKGROUND: Although transcatheter aortic valve implantation has been developing
      as an alternative treatment in elderly patients with high surgical risk, age
      specific differences in clinical outcome have not been fully validated. METHODS:
      Data were analyzed for 2,254 patients at least 80 years old who were enrolled
      between January 2010 and October 2011 in the French national transcatheter aortic
      valve implantation registry, FRANCE-2. Procedural and clinical outcomes defined
      according to the Valve Academic Research Consortium criteria were compared among
      subjects in three age groups: 80 to 84 years (n = 867), 85 to 89 years (n =
      1,064), and at least 90 years (n = 349; range, 90 to 101 years). RESULTS: The
      self-expandable prosthesis was implanted in 710 patients, and the balloon
      expandable prosthesis was implanted in 1,544 patients. No differences were
      observed in rates of procedural success, Valve Academic Research Consortium
      defined complications, and length of hospitalization among groups. Cumulative 30
      day mortalities did not change among the three groups (80 to 84 years, 10.3%
      versus 85 to 89 years, 9.5% versus >= 90 years, 11.2%; p = 0.53). Cumulative 1
      year mortalities also showed no statistical differences, although the mortality
      rate was higher in patients 85 to 89 years old and at least 90 years old compared
      with those 80 to 84 years old (19.8% versus 26.1% versus 27.7%; p = 0.16). After
      adjustment for differential baseline characteristics and potential confounders,
      patient age (85 to 89 years and >= 90 years compared with 80 to 84 years) was not
      associated with increasing risk of 30-day mortality (hazard ratio, 0.92, 1.26;
      95% confidence interval, 0.66 to 1.27, 0.83 to 1.94; p = 0.38, 0.28,
      respectively) and 1-year mortality (hazard ratio, 1.16, 1.36; 95% confidence
      interval, 0.90 to 1.49, 0.97 to 1.89; p = 0.25, 0.073, respectively).
      CONCLUSIONS: This study revealed acceptable clinical results of transcatheter
      aortic valve implantation even in very elderly populations.

PMID- 24140212
TI  - Clinical and angiographic results after hybrid coronary revascularization.
AB  - BACKGROUND: With hybrid coronary revascularization (HCR), minimally invasive left
      internal mammary artery (LIMA) to left anterior descending coronary artery (LAD)
      grafting is combined with percutaneous coronary intervention (PCI) of non-LAD
      vessels. The purpose of this study was to examine the short-term clinical and
      angiographic results in one of the largest HCR series to date. METHODS: From 2003
      to 2012, 300 consecutive patients (aged 64+/-12 years, female 31.7%, predicted
      risk of mortality 1.6%+/-2.1%) underwent HCR on an intent-to-treat basis at a
      single institution. After robotic or thoracoscopic LIMA harvest, off-pump LIMA to
      LAD grafting was performed through a 3- to 4-cm sternal-sparing, non-rib
      spreading thoracotomy. PCI was utilized to treat non-LAD lesions either before,
      after, or concomitant with the surgical procedure. RESULTS: Of the 300 patients
      undergoing HCR on an intent-to-treat basis, HCR was performed with surgery first
      in 192 patients (64.0%), PCI first in 56 (18.7%), and as a concomitant procedure
      in 21 (7.0%). Of the 31 patients (10.1%) who did not undergo HCR, 24 patients
      (8.0%) did not have PCI and thus were incompletely revascularized. For all
      patients, 30-day mortality, stroke, and nonfatal myocardial infarction occurred
      in 4 (1.3%), 3 (1.0%), and 4 (1.3%), respectively. Angiographic LIMA evaluation
      was performed in 248 patients and revealed a FitzGibbon A LIMA patency rate of
      97.6% (242 of 248 patients). Repeat revascularization was required in 13 of 300
      patients (4.3%). CONCLUSIONS: Hybrid coronary revascularization represents an
      alternative approach for patients with multivessel coronary disease with
      excellent short-term outcomes. It provides a minimally invasive alternative to
      traditional coronary artery bypass graft surgery and may prove more durable than
      multivessel PCI.

PMID- 24140211
TI  - HeartWare and HeartMate II left ventricular assist devices as bridge to
      transplantation: a comparative analysis.
AB  - BACKGROUND: The purpose of this study is to comparatively analyze outcomes of
      heart transplant patients bridged to transplantation with HeartWare (HW-VAD)
      versus HeartMate II (HMII-VAD) left ventricular assist devices. METHODS: The
      United Network for Organ Sharing Database was reviewed to identify first-time
      heart transplant recipients who were bridged to transplantation with either HW
      VAD (n=141) or HMII-VAD (n=1824) from January 2009 through July 2012. RESULTS:
      Recipients of HW-VAD had a higher proportion of female patients (27.0% versus
      18.9%; p=0.019), a lower body surface area (2.01+/-0.25 m2 versus 2.06+/-0.25 m2;
      p=0.035), and a trend toward a higher peak percentage of panel reactive antibody
      against human leukocyte class I antigens (40.4%+/-32.8% versus 33.0%+/-30.4%;
      p=0.070). Pretransplantation recipient cardiac index (2.33+/-0.66 L?min(-1)?m(-2)
      versus 2.33+/-0.68 L?min(-1)?m(-2)), serum creatinine (1.21+/-0.43 mg/dL versus
      1.26+/-0.57 mg/dL), and total bilirubin (1.34+/-3.45 mg/dL versus 1.06+/-1.84
      mg/dL) were comparable between the two groups (p>0.05 for all comparisons). After
      transplantation, there were no significant differences in freedom from rejection
      or freedom from cardiac allograft vasculopathy. Posttransplant graft survival
      rates were similar between the HW-VAD group and the HMII-VAD group at 1, 2, and 3
      years (88.4% versus 87.8%, 79.9% versus 83.8%, and 77.4% versus 79.9%,
      respectively; p=0.843). CONCLUSIONS: These findings suggest similar hemodynamic
      unloading, pretransplant end-organ function, and posttransplant outcomes in
      patients bridged to transplantation with both the HW-VAD and HMII-VAD.

PMID- 24140213
TI  - Surviving 20 years after heart transplantation: a success story.
AB  - BACKGROUND: We report the long-term outcomes of patients who survived 20 years or
      greater after heart transplantation. METHODS: From 1985 to 2012, 386 patients
      underwent heart transplantation at our institution. Patient data were analyzed
      retrospectively for transplants performed from 1985 to 1991. The Kaplan-Meier
      method was used for survival analyses. RESULTS: In total, 133 patients were
      included. The mean age of the 20-year survivors at transplant was 43.6+/-11.4
      years. The mean ischemic time was 71.2+/-34.0 minutes. The overall actuarial
      survival rates at 1, 10, and 20 years were 82.7%, 63.9%, and 55.6%, respectively.
      The most common causes of death were graft rejection (21%), malignancy (21%),
      infection (15%), and cardiac allograft vasculopathy (CAV, 14%). After 1, 10, and
      20 years, the rejection-free survival rates were 19%, 13%, and 13%, respectively,
      and the malignancy-free survival rates were 99%, 67%, and 61%. The CAV-free
      survival rates were 97%, 48%, and 42%, respectively, and the infection-free
      survival rates were, respectively, 70%, 15%, and 14%. The actuarial diabetes-free
      survival rates at 1, 10, and 20 years were 85%, 80%, and 79%, respectively.
      Actuarial hypertension-free survival was 56% after 1 year and 26% after 10 and 20
      years. Two patients received a second heart transplant. CONCLUSIONS: A remarkable
      number of patients survived 20 years or greater after heart transplantation,
      confirming the procedure as the gold standard for end-stage heart failure.
      Complications resulting from immunologic events and immunosuppressive therapy
      determine post-transplant mortality and morbidity. Due to improvements in
      immunosuppressive management in recent years, long-term survival is likely to
      increase.

PMID- 24140214
TI  - What is the prevalence of a "nontherapeutic" thymectomy?
AB  - BACKGROUND: Thymectomy is often performed on the basis of computed tomography
      scan findings that are suspicious for thymoma. However, the final diagnosis may
      be a condition such as thymic hyperplasia or lymphoma for which thymectomy is not
      therapeutic. The present analysis was undertaken to determine the prevalence of a
      "nontherapeutic" thymectomy. METHODS: The Nationwide Inpatient Sample from 2000
      through 2009 was queried to identify patients who underwent a thymectomy. Only
      adult patients who underwent a total thymectomy without other associated
      procedures were analyzed. Patients with a diagnosis of myasthenia were excluded.
      A nontherapeutic thymectomy was defined as a patient who underwent thymectomy
      with an International Classification of Diseases, Ninth Revision diagnosis code
      of lymphoma, thymic hyperplasia, thymic cyst, or other benign diseases of the
      thymus. RESULTS: A total of 1,306 patients were identified. Overall, 72.2% (n =
      943) of thymectomies were therapeutic and 27.8% (n = 363) were nontherapeutic.
      The most common diagnosis in the nontherapeutic group was thymic hyperplasia (n =
      174). Mortality (0.32% versus 0%; p = 0.083) and overall complication rates (25%
      versus 17%; p < 0.001) were higher in the therapeutic group. Patients in the
      nontherapeutic group were younger (median age, 41 versus 56 years; p < 0.001) and
      more likely to undergo a video-assisted thoracoscopic surgery thymectomy (28%
      versus 19%; p = 0.085). CONCLUSIONS: In this study, 27.8% of thymectomies were
      nontherapeutic, and most patients underwent an open approach. The most common
      benign diagnosis was thymic hyperplasia, a condition for which magnetic resonance
      imaging has a high predictive value. Consequently, further studies are warranted
      to determine the optimal evaluation of patients undergoing thymectomy for
      presumed thymoma.

PMID- 24140215
TI  - Interrupted commissural band annuloplasty for degenerative mitral valve disease.
AB  - BACKGROUND: Mitral annuloplasty is useful for treating degenerative mitral valve
      disease. Although the incidence of complications is low, prosthetic ring-related
      complications can occur. Hemolysis and mitral stenosis are serious complications
      requiring reoperation. Limited use of prosthetic material could decrease the risk
      for complications. Commissural annuloplasty has been reported by Kay and Reed;
      their techniques involve suture plication. To prevent dehiscence, we selected
      short bands and compared the echocardiographic changes between this method and
      the Cosgrove ring. METHODS: Three sutures are placed in the commissures using two
      bands, which shortens the annular length by 60%. We performed this interrupted
      commissural band annuloplasty (iCBA) in 63 patients and used Cosgrove bands for
      58 patients. RESULTS: Clinically, for iCBA and Cosgrove groups, respectively,
      hemolysis with mild mitral regurgitation occurred in 0 and 2 cases (p=0.084), and
      mitral stenosis due to pannus formation occurred in 0 and 1 case (p=0.224). There
      was a trend toward a lower ring-related complication rate in the iCBA group. On
      echocardiography, for the iCBA and Cosgrove groups, respectively, the maximum
      anterior-posterior distance of the annulus in diastole was 3.1+/-0.7 mm and 2.6+/
      0.4 mm (p<0.001), maximum opening angle of the posterior leaflet was 85.7+/-17.3
      degrees and 103.4+/-20.1 degrees (p<0.001), and coaptation distance was 11.6+/
      3.7 mm and 8.4+/-2.6 mm (p<0.001). CONCLUSIONS: The iCBA method prevented
      posterior leaflet tethering, kept the coaptation distance deep on
      echocardiography, and was associated with lower trends of ring-related
      complications. Because the posterior side of the annulus was not reconstructed,
      iCBA is suitable for fibroelastic deficiency, rather than for Barlow's disease.

PMID- 24140216
TI  - Clinical outcome after triple-valve operations in the modern era: are elderly
      patients at increased surgical risk?
AB  - BACKGROUND: Despite modern advances in surgical care, triple-valve surgery (TVS)
      remains a challenge and carries a mortality of 10% to 20%. No validated risk
      score is available for TVS, and the effect of advanced age is unknown. This study
      examined our results in the modern era with the aim of identifying perioperative
      predictors of adverse outcomes. METHODS: Between 1997 and 2013, 131 patients
      (mean age, 67.2+/-13.4 years) underwent TVS at our institution. Sixty-eight
      patients (51.9%) were aged 70 years and older. The most common etiology for
      aortic and mitral disease was degenerative (77.1%), rheumatic (10%), and
      endocarditis or prosthetic-related, or both, in the rest. Tricuspid valve disease
      was functional in 96%. New York Heart Association functional class III/IV was
      present in 69.4%, and 24% had had previous cardiac operations. One or more
      concomitant cardiac procedures were performed in 77 patients (58.8%), including
      coronary revascularization in 54. All aortic procedures were replacements, 14
      patients required a prosthetic root conduit and 7 thoracic aorta replacement.
      Mitral replacements were used in 55%, repairs in 45%, and 96.2% of tricuspid
      procedures were repairs. Univariate and multivariate analyses were used to
      determine predictors of adverse outcomes. RESULTS: The 30-day and hospital
      mortality was 10.6% (n=14). Major complications occurred in 70 (53.4%).
      Univariate analysis identified New York Heart Association functional class III/IV
      (p=0.04), preoperative renal failure requiring dialysis (p=0.04), urgent
      operation (p=0.04), intraaortic balloon pump placement (p=0.02), and
      postoperative low cardiac output (p<0.0001) as predictors for early death.
      Proximal aortic operations, urgent operation, and New York Heart Association
      class IV correlated with increased early mortality (p<0.04) in patients aged 70
      and older in addition to their decreased overall survival and decreased
      likelihood of discharge to home. Overall actuarial survival at 1, 5, and 10 years
      was 84.5%, 75%, and 45%, respectively. CONCLUSIONS: TVS remains a surgical
      challenge in the modern era. Despite a trend of increasing age and surgical risk,
      the early mortality rate and long-term survival remain respectable. Advanced age
      is associated with increased perioperative risk, but age per se should not be a
      contraindication for TVS.

PMID- 24140217
TI  - Novel diagnosis and treatment of esophageal granular cell tumor: report of 14
      cases and review of the literature.
AB  - BACKGROUND: Granular cell tumors (GCT), especially in the esophagus, are rare
      neoplasms originating from the nervous system. There is still some controversy
      regarding the diagnosis and treatment of esophageal GCT. METHODS: We report 14
      cases of esophageal GCT diagnosed and treated from January 2004 to March 2013.
      Their clinical manifestations, endoscopic image, endoscopic ultrasonography (EUS)
      appearance, pathology, immunohistochemistry, treatment, and prognosis were
      reviewed. RESULTS: The typical images of EUS were hypoechoic, homogenous, and
      smooth-edged tumors restricted to deep mucosal and submucosal layers. However,
      there were 2 cases with tumors invading muscular layer. Endoscopic
      ultrasonography was valuable to assess the tumor size, location, depth of
      invasion, and nature. According to EUS manifestation, 11 cases with lesions 3 cm
      or less in diameter without muscular layer invasion underwent endoscopic
      resection without complication and the other 3 cases underwent surgical
      resection. A new technique of submucosal tunnel endoscopic resection was
      performed in 3 submucosal cases with lesions ranging from 2 cm to 3 cm in
      diameter. All of these cases were benign and histology was necessary for
      differential diagnosis. CONCLUSIONS: Endoscopic ultrasonography plays an
      important guiding role in the diagnosis and treatment of esophageal GCT.
      Submucosal tunnel endoscopic resection is safe and effective. Further study is
      needed to determine whether this technique can be expanded into other
      applications.

PMID- 24140218
TI  - Successes and challenges of establishing a cervical cancer screening and
      treatment program in western Kenya.
AB  - OBJECTIVE: To describe the challenges and successes of integrating a public
      sector cervical screening program into a large HIV care system in western Kenya.
      METHODS: The present study was a programmatic description and a retrospective
      chart review of data collected from a cervical screening program based on visual
      inspection with acetic acid (VIA) between June 2009 and October 2011. RESULTS: In
      total, 6787 women were screened: 1331 (19.6%) were VIA-positive, of whom 949
      (71.3%) had HIV. Overall, 206 women underwent cryotherapy, 754 colposcopy, 143
      loop electrical excision procedure (LEEP), and 27 hysterectomy. Among the
      colposcopy-guided biopsies, 27.9% had severe dysplasia and 10.9% had invasive
      cancer. There were 68 cases of cancer, equating to approximately 414 per 100000
      women per year. Despite aggressive strategies, the overall loss to follow-up was
      31.5%: 27.9% were lost after a positive VIA screen, 49.3% between biopsy and
      LEEP, and 59.6% between biopsy and hysterectomy/chemotherapy. CONCLUSION: The
      established infrastructure of an HIV treatment program was successfully used to
      build capacity for cervical screening in a low-resource setting. By using task
      shifting and evidence-based, low-cost approaches, population-based cervical
      screening in a rural African clinical network was found to feasible; however,
      loss to follow-up and poor pathology infrastructure remain important obstacles.

PMID- 24140219
TI  - Non-immune hydrops fetalis without anemia due to parvovirus B19.

PMID- 24140220
TI  - Antibiotic prophylaxis in prelabor spontaneous rupture of fetal membranes at or
      beyond 36 weeks of pregnancy.
AB  - OBJECTIVE: To assess the effectiveness of prophylactic antibiotics compared with
      placebo in preventing neonatal and maternal infection-related morbidity
      associated with prelabor spontaneous rupture of membranes at or beyond 36 weeks
      of pregnancy. METHODS: In the present randomized controlled trial conducted
      during 2009-2011, 1640 women with prelabor spontaneous rupture of fetal membranes
      at or beyond 36 weeks of pregnancy were randomly assigned to receive a single
      dose of prophylactic intravenous antibiotics or placebo on admission to the labor
      ward of Ain Shams University, Cairo, Egypt. The participants, caregivers, and
      investigators were blinded to the group assignment. The primary outcome measure
      was early-onset neonatal sepsis. An intention-to-treat analysis was performed.
      RESULTS: Early-onset neonatal sepsis occurred in 34 (4.1%) and 24 (2.9%) neonates
      in the antibiotics and placebo groups, respectively (risk ratio 1.42; 95%
      confidence interval 0.85-2.37). Maternal infection outcomes were not
      significantly different between the 2 trial arms. CONCLUSION: The routine use of
      prophylactic antibiotics in women with prelabor spontaneous rupture of fetal
      membranes at or beyond 36 weeks of pregnancy does not reduce the risk of neonatal
      and maternal infection-related morbidity.

PMID- 24140221
TI  - Integrating a complementary medicine consultation for women undergoing
      chemotherapy.
AB  - OBJECTIVE: To explore oncology healthcare providers' (HCPs') patterns of referral
      of women undergoing chemotherapy to a complementary medicine (CM) consultation
      integrated within a conventional oncology service. METHODS: Oncology HCPs used a
      structured referral system for referral to an integrative physician (IP) for CM
      consultation. Referral goals were in accordance with a specified list of quality
      of-life (QOL) outcomes. RESULTS: In total, the study HCPs referred 282 female
      patients, of whom 238 (84.4%) underwent CM consultation by the study IP: 59
      (24.8%) with gynecologic cancer and 179 (75.2%) with non-gynecologic cancer. Use
      of CM for cancer-related outcomes was significantly higher among referred
      patients with gynecologic cancer than those with non-gynecologic cancer (69.5% vs
      46.9%; P=0.003). Oncologists initiated most of the referrals in the gynecologic
      oncology group, whereas oncologic nurses referred most patients in the non
      gynecologic oncology group. Among patients with gynecologic cancer, the
      correlation between HCP indication and patient expectation was high for
      gastrointestinal concerns (kappa 0.41). CONCLUSION: The integration of a
      structured and informed process of referral to CM consultation may enhance
      patient-centered care and QOL during chemotherapy.

PMID- 24140222
TI  - Infertility today: the management of female medical causes.
AB  - It has to be suspected that some environmentally hazardous substances have
      genotoxic properties, revealing their reproductive toxicity at a later stage
      only. Cancer, including childhood cancer, is more common than usually expected.
      Undesirable side effects of surgery, chemotherapy, and/or radiation can be
      premature ovarian failure or even premature menopause. In cases of autoimmune
      disease, autoantibodies can directly affect maturation of oocytes in the
      follicle, fertilization, and implantation. Spontaneous abortions are more common
      in patients with autoimmune disease. Thrombophilia is known to display a higher
      rate of spontaneous abortions as well as pre-eclampsia and intrauterine growth
      retardation. Infections are a common threat to pregnancy. Metabolic syndrome is
      increasingly frequent in western countries and often associated with
      hyperandrogenemia and polycystic disease. Women with inflammatory bowel disease
      such as Crohn disease or ulcerative colitis usually have no problems conceiving.
      In conclusion, even though infertility is a multifactorial disease, various
      medical and non-medical conditions can be attributed to it. 

PMID- 24140223
TI  - Epidemiologic profile, survival, and maternal prognosis factors among women at an
      obstetric intensive care unit.
AB  - OBJECTIVE: To identify the epidemiologic profile, maternal survival, and
      prognosis factors that might affect survival rates in the obstetric intensive
      care unit (ICU). METHODS: A prospective cohort study was conducted between
      January 2007 and February 2009 in a tertiary referral ICU, Belo Horizonte,
      Brazil. Critical patients during pregnancy and puerperium were followed from
      admission until discharge or death. Maternal survival was assessed in association
      with the cause of ICU admission, grouped into direct or indirect obstetric
      causes, by Kaplan-Meier curves and log-rank tests. RESULTS: Among 298 patients
      admitted to the ICU during the study period, mortality was 4.7% (n=14).
      Hypertensive disorders (46.0%), hemorrhage (15.9%), sepsis (14.2%), and heart
      disease (5.7%) were the main causes of admission. Half of the patients who died
      were admitted for direct obstetric reasons (n=7). Survival was statistically
      linked to the cause of admission: most survivors were admitted for a direct
      obstetric cause (75.5%; P=0.044). Maternal survival rates of patients admitted
      for indirect obstetric causes were lower than those admitted for direct obstetric
      causes (27.8 and 19.6 days, respectively; P=0.019). CONCLUSION: The main cause of
      admission was a decisive factor for maternal survival in the obstetric ICU.
      Direct obstetric complications had a better prognosis.

PMID- 24140224
TI  - Bereavement and common mental disorders in middle-aged adults: results from the
      Brazilian longitudinal study of adult health (ELSA-Brasil).
AB  - BACKGROUND: Although bereavement is accompanied with depression and anxiety
      symptoms, it is usually not associated with increased rates of mental disorders
      in North American and European samples. Data from low- and middle-income
      countries are, however, scarce. We therefore explored the prevalence of mental
      disorders after bereavement in Brazil. METHODS: The Clinical Interview Schedule
      Revised (CIS-R) was used for psychiatric assessment of 15,105 participants from
      the Brazilian Health Longitudinal Study (ELSA-Brasil). We asked whether the
      participant suffered loss of a first-degree relative/spouse within 6 and 12
      months prior to the interview. RESULTS: The prevalence within 6 and 12 months
      after bereavement for major depressive disorder (MDD, 4.3% for 6 and 12 months)
      and anxiety disorders (17.4% and 15.9%, respectively) did not differ compared to
      non-bereaved participants, except for panic disorder. Sociodemographic and
      clinical data were also similar. Conversely, we found increased 12-month
      prevalence of bereaved-related (vs. non-related) mixed anxiety and depressive
      disorder (15.7% vs. 12.5%, respectively) and common mental disorder (30.7% vs.
      26.2%); diagnoses that are solely based on the number and severity of depression
      and anxiety symptoms. LIMITATIONS: Although this was a cross-sectional study, the
      sample size was large. CONCLUSIONS: Bereavement was associated with greater
      psychopathological burden but not with increased prevalence of MDD and anxiety
      disorder diagnoses, therefore highlighting the need of carefully monitoring
      subjects whom recently experienced bereavement. Our findings also support and
      provide a "cultural validator" for excluding bereavement as an exclusionary
      criterion for MDD diagnosis.

PMID- 24140225
TI  - Increased energy/activity, not mood changes, is the core feature of mania.
AB  - BACKGROUND: In the Diagnostic and Statistical Manual of Mental Disorders, 5th
      edition, the occurrence of increased energy/activity and elation of mood or
      irritability became necessary symptoms for the diagnosis of an episode of mania
      or hypomania. OBJECTIVE: To evaluate whether increases in energy/activity or mood
      changes represent the core feature of the manic syndrome. METHODS: The
      symptomatology of 117 hospitalized patients with bipolar mania was evaluated
      using the Schedule for Affective Disorders and Schizophrenia-Changed version
      (SADS-C). Based on six items of the SADS-S related to mania, a Confirmatory
      Factor Analysis (CFA) was performed. An Item Response Theory (IRT) analysis was
      used to identify how much each symptom informs about the different levels of
      severity of the syndrome. RESULTS: According to the CFA, the item "increased
      energy" was the symptom with the highest factorial loadings, which was confirmed
      by the IRT analysis. Thus, increased energy was the alteration most correlated
      with the total severity of manic symptoms. Additionally, the analysis of the Item
      Information Function revealed that increased energy was correlated with the
      larger amplitude of severity levels compared with the other symptoms of mania.
      LIMITATIONS: Only six manic symptoms were considered. The sample might not be
      representative because the patients were evaluated while presenting peak symptom
      severity. CONCLUSIONS: Increased energy/activity is a more important symptom for
      a diagnosis of mania than mood changes and represents the core feature of this
      syndrome.

PMID- 24140226
TI  - A comparison of cognitive-behavioral therapy, antidepressants, their combination
      and standard treatment for Chinese patients with moderate-severe major depressive
      disorders.
AB  - BACKGROUND: No study has examined the effect of cognitive-behavioral therapy
      (CBT) on moderate-severe major depressive disorders (MDD) in China. The objective
      of this study was to evaluate the effect of CBT, antidepressants alone (MED),
      combined CBT and antidepressants (COMB) and standard treatment (ST; i.e.,
      receiving psycho-educational intervention and/or medication treatment determined
      by treating psychiatrists) on depressive symptoms and social functioning in
      Chinese patients with moderate-severe MDD. METHOD: A total of 180 patients
      diagnosed with MDD according to ICD-10 were randomly allocated to one of the four
      treatment regimens for a period of 6 months. Depressive symptoms were measured
      using the Hamilton Rating Scale for Depression (HAMD) and the Quick Inventory of
      Depressive Symptomatology-Self-Report (C-QIDS-SR). Remission threshold was
      defined as a C-QIDS-SR total score of <5. Social functioning was evaluated with
      the Work and Social Adjustment Scale (WSAS). All outcome measures were evaluated
      at entry, and at 3- and 6-months follow-up. RESULTS: At the 6-months assessment,
      the remission rates in the whole sample (n=96), the MED, the CBT, the COMB and
      the ST groups were 54.2%, 48%, 75%, 53.5% and 50%, respectively. Following the
      treatment periods, there was no significant difference in any of the study
      outcomes between the four groups. However, the CBT showed the greatest effect in
      the HAMD total score with the effect size=0.94, whereas the ST has only a
      moderate effect size in the WSAS total score (effect size=0.47). CONCLUSIONS: The
      findings support the feasibility and effectiveness of CBT as a psychosocial
      intervention for Chinese patients with moderate-severe MDD. We also found that
      single treatment using MED or CBT performed equally well as the combined CBT
      antidepressant treatment in controlling the remission. The study provided
      important knowledge to inform the mental health care planning in China.

PMID- 24140227
TI  - Effect of lungeing on head and pelvic movement asymmetry in horses with induced
      lameness.
AB  - Lungeing is an important part of lameness examinations, since the circular path
      enforced during lungeing is thought to accentuate low grade lameness. However,
      during lungeing the movement of sound horses becomes naturally asymmetric, which
      may mimic lameness. Also, compensatory movements in the opposite half of the body
      may mimic lameness. The aim of this study was to objectively study the presence
      of circle-dependent and compensatory movement asymmetries in horses with induced
      lameness. Ten horses were trotted in a straight line and lunged in both
      directions on a hard surface. Lameness was induced (reversible hoof pressure) in
      each limb, one at a time, in random order. Vertical head and pelvic movements
      were measured with body-mounted, uni-axial accelerometers. Differences between
      maximum and minimum height observed during/after left and right stance phases for
      the head (HDmax, HDmin) and pelvis (PDmax, PDmin) were measured. Mixed models
      were constructed to study the effect of lungeing direction and induction, and to
      quantify secondary compensatory asymmetry mechanisms in the forelimbs and hind
      limbs. Head and pelvic movement symmetries were affected by lungeing. Minimum
      pelvic height difference (PDmin) changed markedly, increasing significantly
      during lungeing, giving the impression of inner hind limb lameness. Primary hind
      limb lameness induced compensatory head movement, which mimicked an ipsilateral
      forelimb lameness of almost equal magnitude to the primary hind limb lameness.
      This could contribute to difficulty in correctly detecting hind limb lameness.
      Induced forelimb lameness caused both a compensatory contralateral (change in
      PDmax) and an ipsilateral (change in PDmin) hind limb asymmetry, potentially
      mimicking hind limb lameness, but of smaller magnitude. Both circle-dependent and
      compensatory movement mechanisms must be taken into account when evaluating
      lameness. 

PMID- 24140228
TI  - Pressure plate analysis of toe-heel and medio-lateral hoof balance at the walk
      and trot in sound sport horses.
AB  - Empirically, equine distal limb lameness is often linked to hoof imbalance. To
      objectively quantify dynamic toe-heel and medio-lateral hoof balance of the
      vertical ground reaction force in sound sport horses, seven Royal Dutch Sport
      Horses were led at the walk and trot over a dynamically calibrated pressure
      plate. Forelimb hoof prints were divided into a toe and heel region and a medial
      and lateral zone. Toe-heel and medio-lateral hoof balance of the vertical ground
      reaction force were calculated throughout the stance. Toe-heel balance was highly
      symmetrical between contralateral limbs at both gaits. At the walk, medio-lateral
      balance of both forelimbs presented higher loading in the lateral part of the
      hoof throughout the stance. However, at the trot, left medio-lateral balance
      presented higher loading of the medial part of the hoof at impact, whereas the
      right limb showed higher loading of the lateral part of the hoof in all horses,
      and both limbs presented increased lateral loading at the end of the stance. This
      study provides objective data for toe-heel and medio-lateral hoof balance in
      sound sport horses. 

PMID- 24140229
TI  - Locomotion moves on.

PMID- 24140230
TI  - Protective role of adenylate cyclase in the context of a live pertussis vaccine
      candidate.
AB  - Despite high vaccination coverage, pertussis remains an important respiratory
      infectious disease and the least-controlled vaccine-preventable infectious
      disease in children. Natural infection with Bordetella pertussis is known to
      induce strong and long-lasting immunity that wanes later than vaccine-mediated
      immunity. Therefore, a live attenuated B. pertussis vaccine, named BPZE1, has
      been developed and has recently completed a phase I clinical trial in adult human
      volunteers. In this study, we investigated the contribution of adenylate cyclase
      (CyaA) in BPZE1-mediated protection against pertussis. A CyaA-deficient BPZE1
      mutant was thus constructed. Absence of CyaA did not compromise the adherence
      properties of the bacteria onto mammalian cells. However, the CyaA-deficient
      mutant displayed a slight impairment in the ability to survive within macrophages
      compared to the parental BPZE1 strain. In vivo, whereas the protective efficacy
      of the CyaA-deficient mutant was comparable to the parental strain at a vaccine
      dose of 5 * 10(5) colony forming units (CFU), it was significantly impaired at a
      vaccine dose of 5 * 10(3) CFU. This impairment correlated with impaired lung
      colonization ability, and impaired IFN-gamma production in the animal immunized
      with the CyaA-deficient BPZE1 mutant while the pertussis-specific antibody
      profile and Th17 response were comparable to those observed in BPZE1-immunized
      mice. Our findings thus support a role of CyaA in BPZE1-mediated protection
      through induction of cellular mediated immunity. 

PMID- 24140231
TI  - Evaluation of CK2 inhibitor (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA)
      in regulation of platelet function.
AB  - Casein Kinase II (CK2) is a serine/threonine kinase which is expressed in
      platelets. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a
      substrate of CK2 and antagonizes PI 3-kinase-mediated pathways by
      dephosphorylating phosphatidylinositol 3,4,5-triphosphate (PIP3). Since the role
      of CK2 and its signaling mechanism in platelet activation is not understood, we
      have examined whether CK2 plays an important role in agonist-induced platelet
      functional responses through the regulation of PI 3-kinase pathways by using a
      new class of highly selective CK2 inhibitor TBCA [(E)-3-(2,3,4,5
      tetrabromophenyl)acrylic acid]. TBCA dose-dependently inhibited platelet
      aggregation and secretion induced by various agonists including 2-MeSADP, AYPGKF,
      SFLLRN, and CRP. Extent of platelet response inhibited by TBCA was similar to the
      extent of inhibition induced by PI 3-kinase inhibitors. CK2 regulated
      phosphorylation of PTEN as the inhibition of CK2 resulted in the inhibition of
      AYPGKF-induced PTEN phosphorylation. Agonist-induced thromboxane A2 (TxA2)
      generation and ERK phosphorylation were significantly inhibited by TBCA. TBCA
      also inhibited phosphorylation of PDK1, Akt, and GSK3beta induced by AYPGKF.
      However, CK2 inhibition had no effect on AYPGKF-induced phosphorylation of PKC
      substrate plekstrin, demonstrating the selective action of TBCA through Gi
      mediated PI 3-kinase pathways. Finally, platelet spreading on immobilized
      fibrinogen surface and clot retraction mediated by integrin alphaIIbbeta3
      signaling were significantly inhibited in the presence of TBCA. We conclude that
      CK2 plays a key role in platelet aggregation, secretion, TxA2 generation, and Akt
      and ERK phosphorylation, through the regulation of PI 3-kinase pathways.
      Moreover, CK2 is involved in alphaIIbbeta3-mediated outside-in signaling in
      platelets. 

PMID- 24140232
TI  - Environmental sensing and regulation of gene expression in CD4+ T cell subsets.
AB  - Foxp3(+) regulatory T (Treg) cells represent a major mechanism for the
      maintenance of self-tolerance and immune homeostasis in various inflammatory
      responses. To achieve this, Foxp3(+) Treg cells must integrate a spectrum of
      environmental stimuli to orchestrate the required pathways for their coordinated
      action in vivo. Transcriptional and post-transcriptional mechanisms of gene
      regulation enable T cells to respond to inflammatory events, by altering the
      nature, amounts and activities of specific proteins produced for their controlled
      and coordinated modulation of immunity. Recent studies show that distinct
      translational programs orchestrate cellular processes in various immune cell
      types, including CD4(+) T cell subsets. 

PMID- 24140233
TI  - Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids
      in patients with advanced pancreatic cancer.
AB  - BACKGROUND & AIMS: Omega-3 rich fatty acids (n-3FA) have powerful anti
      inflammatory and anti-neoplastic properties. Previous studies have investigated
      plasma and cellular uptake of oral and parenteral n-3FA regimens. These have
      shown that n-3FA undergo rapid uptake into cells which is sustained for the
      length of the treatment course. The aim of this study was to investigate long
      term uptake of prolonged, regular treatment courses of parenteral n-3FA which has
      not been previously reported. METHODS: As part of a phase II single-arm trial,
      patients with advanced pancreatic cancer were treated with gemcitabine plus
      parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three
      consecutive weeks with a subsequent rest week. This was repeated for up to six
      months in total for each patient. Pre-treatment serum and erythrocyte cell
      membrane (ECM) pellet samples were obtained each week for the entire treatment
      course of each patient. Post-treatment samples were obtained for the first two
      cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced
      and analysed using gas chromatography. FAME proportions as a total of sample
      lipid composition for each class were plotted and the results analysed using a
      linear regression coefficient model. RESULTS: There was rapid and significant
      uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA
      into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and
      0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and
      DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all).
      There was significant sustained uptake of EPA and DHA FAME into ECM pellets over
      the cohort's pooled treatment course with corresponding reduction in the n-6:n-3
      ratio. CONCLUSIONS: Prolonged regular parenteral n-3FA administration results in
      rapid and sustained cellular uptake. This regimen is appropriate for therapies
      aimed at increasing n-3FA content of cellular membranes and reduction of the n
      6:n-3 ratio.

PMID- 24140234
TI  - A positive association of vitamin D deficiency and sarcopenia in 50 year old
      women, but not men.
AB  - BACKGROUND & AIMS: Sarcopenia, loss of muscle mass and function, is one of the
      major risk factors for metabolic diseases and vitamin D is also positively
      associated with their prevalence. We examined whether vitamin D deficiency was
      positively associated with sarcopenia in a gender-specific manner in adults aged
      >=50 years, independent of other covariates and possible confounders, including
      body composition, blood tests, including serum parathyroid hormone (PTH) levels,
      dietary intake, and hormone replacement therapy in women. METHODS: This cross
      sectional study included 2258 men and 3005 women aged >=50 years who participated
      in the 2009-2010 Korean National Health and Nutrition Examination Survey.
      Sarcopenia was defined as appendicular skeletal muscle mass/body weight <2
      standard deviations below gender-specific means for young adults. Vitamin D
      status was represented by serum 25-hydroxyvitamin D (25-OH-D) levels. Adjusted
      odds ratios for having sarcopenia were calculated according to vitamin D status,
      while controlling for covariates that affect vitamin D status and body
      composition using logistic regression analysis with incorporating the sample
      weights for the complex sample design of the survey. RESULTS: Sarcopenia showed a
      strong inverse association with serum 25-OH-D levels in women, but not men,
      independent of other covariates and possible confounders. Sarcopenia was
      negatively associated with dietary intakes of energy, protein, and carbohydrates
      in both men and women, but walking and exercise showed no significant
      relationship with sarcopenic status. Sarcopenic status was significantly
      associated with serum total 25-OH-D and cholesterol levels only in women and with
      serum PTH levels only in men. The risk of sarcopenia was increased, by 1.46-fold,
      by lowering serum 25-OH-D by 10 ng/mL only in women. CONCLUSIONS: Serum 25-OH-D
      levels were a negative modulator of sarcopenia only in women aged >=50 years in a
      Korean population.

PMID- 24140235
TI  - Will weight loss cause significant dosimetric changes of target volumes and
      organs at risk in nasopharyngeal carcinoma treated with intensity-modulated
      radiation therapy?
AB  - This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal
      carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT).
      Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated
      weight loss during IMRT on the computer. Weight loss model was based on the
      planning computed tomography (CT) images. The original external contour of head
      and neck was labeled plan 0, and its volume was regarded as pretreatment normal
      weight. We shrank the external contour with different margins (2, 3, and 5mm) and
      generated new external contours of head and neck. The volumes of reconstructed
      external contours were regarded as weight during radiotherapy. After recontouring
      outlines, the initial treatment plan was mapped to the redefined CT scans with
      the same beam configurations, yielding new plans. The computer model represented
      a theoretical proportional weight loss of 3.4% to 13.7% during the course of
      IMRT. The dose delivered to the planning target volume (PTV) of primary gross
      tumor volume and clinical target volume significantly increased by 1.9% to 2.9%
      and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of
      gross tumor volume of lymph nodes fluctuated from -2.0% to 1.0%. The dose to the
      brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the
      parotid gland was decreased (p < 0.001). Weight loss may lead to significant
      dosimetric change during IMRT. Repeated scanning and replanning for patients with
      NPC with an obvious weight loss may be necessary. 

PMID- 24140236
TI  - MicroRNA deregulation in right ventricular outflow tract myocardium in
      nonsyndromic tetralogy of fallot.
AB  - BACKGROUND: Tetralogy of Fallot (TOF) is 1 of the most common heart defects in
      children, and the underlying mechanisms remain largely elusive. MicroRNAs
      (miRNAs) are a class of regulators of gene expression and are increasingly
      recognized for their roles in heart development. METHODS: To identify miRNAs
      abnormally expressed in TOF, microarrays were used to analyze the miRNA
      expression profiles of 5 samples of myectomy tissues from right ventricular
      outflow tract (RVOT) obstruction of infants with nonsyndromic TOF and 3 age
      matched normal RVOT tissues. RESULTS: In total, 41 candidate miRNAs were
      identified. To further validate the microarray results, the 41 miRNAs were
      detected using quantitative reverse transcriptase polymerase chain reaction (qRT
      PCR) in a larger independent population of tissue samples, including 21 from
      patients with TOF and 6 from normal controls; it was found that 18 miRNAs were
      expressed at significantly different levels. Bioinformatic analysis revealed that
      these miRNAs targeted a network of genes involved in heart development and human
      congenital heart diseases. Further in vitro studies indicated that upregulation
      of miR-424/424* promoted proliferation and inhibited migration of primary
      embryonic mouse cardiomyocytes, whereas miR-222 promoted cardiomyocyte
      proliferation and reduced the cardiomyogenic differentiation of P19 cells. The
      3'UTR (3' untranslated region) luciferase assay revealed that miR-424/424*
      suppressed the expression of HAS2 and NF1, and their mRNAs were underexpressed in
      the RVOT myocardial tissues of TOF. CONCLUSIONS: Eighteen miRNAs were identified
      as being deregulated in RVOT myocardial tissues from infants with nonsyndromic
      TOF, and in vitro experiments indicated that miR-424/424* and miR-222 are
      involved in cardiomyocyte proliferation and migration and the cardiomyogenic
      differentiation of P19 cells.

PMID- 24140237
TI  - Lack of correlation between air pollution and acute-onset atrial fibrillation.

PMID- 24140238
TI  - Atrial pacing in sick sinus syndrome: still plausible?

PMID- 24140239
TI  - Effect of deforestation and introduction of exotic grasses as livestock forage on
      the population dynamics of the cattle tick Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae) in northern Argentina.
AB  - The effect of deforestation and the introduction of exotic grasses on the
      population dynamics of Rhipicephalus (Boophilus) microplus in northern Argentina
      was analysed. Biological parameters that were measured included proportion of
      females ovipositing, pre-oviposition period, incubation period of eggs,
      proportion of egg clusters hatching, larval longevity and total non-parasitic
      period. No significant differences were observed in proportion of females
      ovipositing and in pre-oviposition period between forested and grassland areas.
      Regarding the other parameters, in the majority of the temporal series there were
      no significant differences. In the cases where differences with statistical
      significance were detected, they were not unidirectional. The replacement of
      native forest by grasses can potentially increase tick abundance not by the
      modification of microclimatic conditions, but by increasing the tick-host
      encounter rate due to a higher cattle density. The hypothesis that deforestation
      and introduction of exotic grasses affects the non-parasitic phase of R.
      microplus in northern Argentina was not supported. 

PMID- 24140240
TI  - Towards the harnessing of gut feelings.

PMID- 24140241
TI  - Social communication mediates the relationship between emotion perception and
      externalizing behaviors in young adult survivors of pediatric traumatic brain
      injury (TBI).
AB  - Traumatic brain injury (TBI) is a common cause of childhood disability, and is
      associated with elevated risk for long-term social impairment. Though social
      (pragmatic) communication deficits may be among the most debilitating
      consequences of childhood TBI, few studies have examined very long-term
      communication outcomes as children with TBI make the transition to young
      adulthood. In addition, the extent to which reduced social function contributes
      to externalizing behaviors in survivors of childhood TBI remains poorly
      understood. The present study aimed to evaluate the extent of social
      communication difficulty among young adult survivors of childhood TBI (n=34,
      injury age: 1.0-7.0 years; M time since injury: 16.55 years) and examine
      relations among aspects of social function including emotion perception, social
      communication and externalizing behaviors rated by close-other proxies. Compared
      to controls the TBI group had significantly greater social communication
      difficulty, which was associated with more frequent externalizing behaviors and
      poorer emotion perception. Analyses demonstrated that reduced social
      communication mediated the association between poorer emotion perception and more
      frequent externalizing behaviors. Our findings indicate that socio-cognitive
      impairments may indirectly increase the risk for externalizing behaviors among
      young adult survivors of childhood TBI, and underscore the need for targeted
      social skills interventions delivered soon after injury, and into the very long
      term. 

PMID- 24140242
TI  - Inflammatory response and oxidative stress in developing rat brain and its
      consequences on motor behavior following maternal administration of LPS and
      perinatal anoxia.
AB  - Cerebral palsy (CP) is a disorder of locomotion, posture and movement that can be
      caused by prenatal, perinatal or postnatal insults during brain development. An
      increased incidence of CP has been correlated to perinatal asphyxia and maternal
      infections during gestation. The effects of maternal exposure to low doses of
      bacterial endotoxin (lipopolysaccharide, LPS) associated or not with perinatal
      anoxia (PA) in oxidative and inflammatory parameters were examined in cerebral
      cortices of newborns pups. Concentrations of TNF-alpha, IL-1, IL-4, SOD, CAT and
      DCF were measured by the ELISA method. Other newborn rats were assessed for
      neonatal developmental milestones from day 1 to 21. Motor behavior was also
      tested at P29 using open-field and Rotarod. PA alone only increased IL-1
      expression in cerebral cortex with no changes in oxidative measures. PA also
      induced a slight impact on development and motor performance. LPS alone was not
      able to delay motor development but resulted in changes in motor activity and
      coordination with increased levels of IL-1 and TNF-alpha expression associated
      with a high production of free radicals and elevated SOD activity. When LPS and
      PA were combined, changes on inflammatory and oxidative stress parameters were
      greater. In addition, greater motor development and coordination impairments were
      observed. Prenatal exposure of pups to LPS appeared to sensitize the developing
      brain to effects of a subsequent anoxia insult resulting in an increased
      expression of pro-inflammatory cytokines and increased free radical levels in the
      cerebral cortex. These outcomes suggest that oxidative and inflammatory
      parameters in the cerebral cortex are implicated in motor deficits following
      maternal infection and perinatal anoxia by acting in a synergistic manner during
      a critical period of development of the nervous system. 

PMID- 24140243
TI  - Physical workload, trapezius muscle activity, and neck pain in nurses' night and
      day shifts: a physiological evaluation.
AB  - The purpose of this study was to compare physical workload, electromyography
      (EMG) of the trapezius muscle, neck pain and mental well-being at work between
      night and day shifts in twenty Swiss nurses. Work pulse (average increase of
      heart rate over resting heart rate) was lower during night (27 bpm) compared to
      day shifts (34 bpm; p < 0.01). Relative arm acceleration also indicated less
      physical activity during night (82% of average) compared to day shifts (110%; p <
      0.01). Rest periods were significantly longer during night shifts. Trapezius
      muscle rest time was longer during night (13% of shift duration) than day shifts
      (7%; p < 0.01) and the 50th percentile of EMG activity was smaller (p = 0.02),
      indicating more opportunities for muscle relaxation during night shifts. Neck
      pain and mental well-being at work were similar between shifts. Subjective
      perception of burden was similar between shifts despite less physical burden at
      night, suggesting there are other contributing factors. 

PMID- 24140244
TI  - Towards identifying the roll motion parameters of a motorcycle simulator.
AB  - This study aimed at identifying the roll motion parameters of a motorcycle
      simulator prototype. Experienced motorcyclists tuned the angular physical
      movement of the mock-up and that of the visual scene to achieve an optimal riding
      experience during curves. The participants exceeded the rolling angles that would
      be required in real-world riding, while avoiding leaning the mock-up beyond 10
      degrees . In addition, they were more influenced by the speed of the virtual
      motorcycle than by road curvature, especially in a wide field of view.
      Heterogeneity was found in the roll applied to the visual scene. The overall
      patterns suggest that at least when washout is not applied to remove the side
      forces that in real-world riding are compensated by a centrifugal force, greater
      roll of the visual at the expense of the mock-up is mandatory to avoid
      performance biases that might be enhanced due to fear of falling off the
      simulator. Future roll motion models must take into consideration factors such as
      riding postures, which might not only influence the forces operating on the rider
      motorcycle system, but also how motorcyclists perceive the visual world. 

PMID- 24140245
TI  - Effect of diabetes mellitus and metformin use on oncologic outcomes of patients
      treated with radical cystectomy for urothelial carcinoma.
AB  - OBJECTIVES: Evidence suggests a positive effect of metformin on cancer incidence
      and outcome. To date, the effect of metformin use on prognosis in urothelial
      carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis
      that metformin use affects oncologic outcomes of patients treated with radical
      cystectomy for UCB. METHODS AND MATERIALS: We retrospectively evaluated 1,502
      patients treated at 4 institutions with radical cystectomy and pelvic
      lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the
      association of diabetes mellitus (DM) and metformin use with disease recurrence,
      cancer-specific mortality, and any-cause mortality. RESULTS: A total of 200
      patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median
      follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402
      patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In
      univariable Cox regression analyses, DM without metformin use was associated with
      increased risk of disease recurrence (hazard ratio [HR]: 1.40, 95% confidence
      interval [CI] 1.05-1.87, P = 0.02), cancer-specific mortality (HR: 1.60, 95% CI
      1.17-2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18-2.03, P =
      0.002), whereas metformin use was associated with decreased risk of disease
      recurrence (HR: 0.61, 95% CI 0.37-0.98, P = 0.04), cancer-specific mortality (HR:
      0.56, 95% CI 0.33-0.97, P = 0.04), and any-cause mortality (HR: 0.54, 95% CI 0.33
      0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without
      metformin use remained associated with worse cancer-specific mortality (HR: 1.53,
      95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00,
      P = 0.003) but not disease recurrence. CONCLUSIONS: Diabetic patients who do not
      use metformin appear to be at higher risk of cancer-specific and any-cause
      mortality than patients without DM. It remains unclear, whether the severity of
      DM in this group of patients or the use of metformin itself affects outcomes of
      UCB. The mechanisms behind the effect of DM on patients with UCB and the
      potential protective effect of metformin need further elucidation.

PMID- 24140246
TI  - Gene-based urinary biomarkers for bladder cancer: an unfulfilled promise?
AB  - OBJECTIVE: Noninvasive biomarkers are used routinely in the clinical management
      of several cancers but bladder cancer detection and surveillance remains
      dependent on invasive procedures such as cystoscopy. No validated biomarker
      currently exists in routine clinical practice other than cytology. Gene-based
      testing has shown great promise for biomarker profiling and this review addresses
      the current state of biomarker research in bladder cancer. MATERIALS AND METHODS:
      A comprehensive review of all published literature on urinary biomarkers from
      1970 - 2012 was conducted in PubMed. Keywords used alone or in combination were
      bladder cancer, diagnosis, surveillance, urinary biomarker, molecular biomarkers,
      methylation, gene expression, single nucleotide polymorphism and microRNA. The
      cited references of the manuscripts included in the review were also screened.
      RESULTS: We have reviewed various strategies currently used for gene-based
      biomarker profiling of bladder cancer. We have comprehensively summarized the
      performance of several biomarkers in the diagnosis and surveillance of bladder
      cancer. Finally we have identified biomarkers that have shown potential and now
      deserve the opportunity to be validated in the clinical setting. CONCLUSION:
      Several gene-based urinary biomarkers have demonstrated promise in initial
      studies, which now need to be rigorously validated in the clinical setting for
      them to be translated into clinically useful tests in diagnosis, surveillance or
      risk-stratification of bladder cancer.

PMID- 24140247
TI  - The effect of photochemical internalization of bleomycin in the treatment of
      urothelial carcinoma of the bladder: an in vitro study.
AB  - OBJECTIVES: In this in vitro study, we determined whether meso-tetraphenyl
      chlorin disulphonate (TPCS2a)-based photochemical delivery of bleomycin was able
      to potentiate the cytotoxicity of bleomycin on bladder cancer cells. MATERIALS
      AND METHODS: The human RT4, RT112, 253J, T24, and rat AY-27 urothelial carcinoma
      cell lines were used. Cells were seeded in 96-well plates. TPCS2a was added to
      the growth medium and the plates were incubated overnight. Cells were then
      resuspended in TPCS2a-free culture medium and incubated for 3 hours.
      Subsequently, cells were treated for 60 minutes with increasing doses of
      epirubicin, gemcitabine, mitomycin C, or bleomycin followed by illumination for
      different periods. Cell viability was measured with a colorimetric assay after 72
      hours. RESULTS: For the single treatments, in all 5 cell lines a dose-dependent
      inhibition of cell proliferation was observed. This was seen both after treatment
      with TPCS2a-based photodynamic therapy (PDT), as well as after treatment with
      either bleomycin or one of the control chemotherapeutic agents. After treatment
      with PDT (240-s illumination), bleomycin 9.0 uM, and the combination of these
      treatments, relative survival percentages were 89.2 +/- 13.0, 70.2 +/- 8.9, and
      30.5 +/- 6.1, respectively, in the T24 cell line. After treatment with PDT (120-s
      illumination), bleomycin 27 uM and the combination of these treatments, relative
      survival percentages were 93.6 +/- 15.7, 74.7 +/- 9.6, and 30.0 +/- 11.1,
      respectively, in the AY-27 cell line. In both cell lines, PDT combined with
      bleomycin showed significantly (P<0.001) higher cell kill than the sum of the
      single treatments, suggesting a photochemical internalization effect.
      CONCLUSIONS: TPCS2a-based photochemical internalization of bleomycin showed a
      significant, at least, additive antiproliferative activity against human and rat
      urothelial carcinoma cells in vitro. Thus, photochemical internalization may have
      therapeutic potential as an intravesical strategy against bladder cancer. As the
      effect is heterogeneous, biomarker studies are warranted to be able to predict
      the effects of a photochemical internalization-based treatment.

PMID- 24140248
TI  - High rates of advanced disease, complications, and decline of renal function
      after radical nephroureterectomy.
AB  - OBJECTIVES: Recurrences remain common following radical nephroureterectomy (RNU)
      for locally advanced upper-tract urothelial carcinoma (UTUC). We review a cohort
      of RNU patients to identify the incidence of locally advanced disease, decline in
      renal function, complications, and utilization of adjuvant chemotherapy (AC).
      METHODS: Institutional databases from 7 academic medical centers identified 414
      RNU patients treated between 2003 and 2012 who had not received neoadjuvant
      chemotherapy. Glomerular filtration rate was estimated using the Modification of
      Diet in Renal Disease equation. Complications were classified according to the
      modified Clavien system. Cox proportional hazard modeling and Kaplan-Meier
      analysis determined factors associated with cancer-specific survival. RESULTS: Of
      414 patients, 177 (43%) had locally advanced disease, including 118 pT3N0/Nx, 13
      pT4N0/Nx, and 46 pTanyN+. Estimated 3- and 5-year cancer-specific survival was
      47% and 34%, respectively. Only 31% of patients with locally advanced UTUC
      received AC. Mean estimated glomerular filtration rate declined from 59 to 51
      ml/min/1.73 m(2) following RNU, including a new-onset decline below 60 and 45
      ml/min/1.73 m(2) in 25% and 15% of patients, respectively (P<0.001 for both).
      Complications occurred in 46 of 177 (26%) patients, of which one-quarter were
      grade III or IV. Increasing age (Hazard Ratio (HR) 1.4, P = 0.03), positive
      surgical margins (HR 2.1, P = 0.01), and positive lymph nodes (HR 4.3, P<0.001)
      were associated with an increased risk of death from UTUC, whereas receipt of AC
      (HR 0.85, P = 0.05) was associated with a decrease in UTUC mortality.
      CONCLUSIONS: Under one-third of RNU patients with locally advanced UTUC cancers
      received AC. Perioperative complications and decline in renal function may have
      contributed to this low rate. Such data further underscore the need for continued
      discussion regarding the use of chemotherapy in a neoadjuvant setting for
      appropriately selected patients with UTUC.

PMID- 24140249
TI  - Human papillomaviruses in urological malignancies: a critical assessment.
AB  - OBJECTIVES: Infection with human papillomaviruses (HPVs) is intimately associated
      with anogenital tract malignancies including cervical and vulvar cancer, a subset
      of oropharyngeal cancers and certain types of skin cancer. A number of urological
      tumors have likewise been suggested to be associated with high-risk HPV
      infection; however, many studies are hampered by a limited number of detection
      methods. The goal of this review article is to define a set of key criteria when
      implicating a virus in a human cancer and to apply these criteria to HPV
      infection in urological cancers. MATERIALS AND METHODS: We performed a survey of
      the literature to corroborate the evidence to support a causal relationship
      between HPV infection and major urological malignancies. RESULTS: A number of
      previous reports have implicated HPVs in urological malignancies including
      penile, prostate, and bladder cancer. Most reports, however, rely only on a
      limited number of detection methods and frequently use contamination-prone
      polymerase chain reaction based methods. To firmly establish a link between a
      viral infection and a human malignancy, it is paramount that an array of
      techniques is employed and that the virus is ultimately traced by either direct
      visualization or, in the case of viral genome that has integrated into the host
      genome, detection of viral genes and gene products as well as functional cellular
      perturbations. In any case, seroepidemiological studies are likewise crucial to
      support the evidence. Such evidence for a role of HPV in urological malignancies
      based on currently available techniques is only present for penile squamous cell
      carcinomas. CONCLUSIONS: An increasing number of immunocompromised patients as
      well as novel developments in patient care may change the spectrum of HPV
      associated neoplasms. This is examplified by results demonstrating a role of HPVs
      in rare urothelial carcinomas with squamous differentiation in patients with
      neurogenic bladder. Hence, it is important to keep HPV infection in mind when
      confronted with unusual disease manifestations of the urogenital tract.

PMID- 24140250
TI  - Activation of cyclic AMP/PKA pathway inhibits bladder cancer cell invasion by
      targeting MAP4-dependent microtubule dynamics.
AB  - OBJECTIVE: With the notorious reputation of the vicious invasion, the bladder
      cancer is the most common malignant tumor of the urinary system. Inhibiting
      invasion through microtubule dynamics interruption has emerged as an important
      treatment of bladder cancer. Here we investigated the role of the cyclic
      adenosine monophosphate/protein kinase A (cAMP/PKA) pathway in human bladder
      cancer cells invasion. MATERIALS AND METHODS: With or without the treatment of
      various cAMP elevators, we assessed invasive and migrated capabilities of T24 and
      UM-UC-3, two high-grade invasive bladder cancer cell lines, using matrigel
      transwell inserts assay and scratch wound healing assay. The microtubule (MT)
      dynamics were examined by immunofluorescence and immunoblotting. Microtubule
      Associated Protein 4 (MAP4) was silenced to investigate its role in tumor
      invasion. We also analyzed gene expression of MAP4 in 34 patients with bladder
      cancer using immunohistochemical staining assay. The interaction between PKA and
      MAP4 was examined by co-immunoprecipitation. RESULTS: We used cAMP elevators and
      small interfering RNA of MAP4 here, found that both of them can potently inhibit
      the invasion and the migration of bladder cancer cells by disrupting microtubule
      (MT) cytoskeleton. Consistently, the bladder cancer grade is positively
      correlated with the protein level of MAP4. Furthermore, we found that cAMP/PKA
      signaling can disrupt MT cytoskeleton by the phosphorylation of MAP4. CONCLUSION:
      Our results indicated that the cAMP/PKA signaling pathway might inhibit bladder
      cancer cell invasion by targeting MAP4-dependent microtubule dynamics, which
      could be exploited for the therapy of invasive bladder cancer.

PMID- 24140251
TI  - No clear evidence for a positive association between the interpersonal-affective
      aspects of psychopathy and executive functioning.
AB  - Common psychopathy rating instruments distinguish between an interpersonal
      affective and an antisocial dimension. The suggestion that the interpersonal
      affective dimension, often considered to be the core feature of psychopathy, is
      positively associated with executive functioning is occasionally made in the
      literature, without reporting objective empirical data. The primary aim of the
      present paper was to search for empirical studies reporting relevant data,
      focussing on four aspects of 'cold' executive functioning: inhibition,
      attentional shifting, working memory, and planning. Eleven published articles
      were identified, reporting data of 721 individuals from incarcerated and non
      incarcerated, male and female, and adult and non-adult samples. Using a
      heterogeneous set of tests and dependent measures across studies, the inhibition
      and attentional shifting components were assessed in eight and five studies,
      respectively; the working memory and planning components each in two studies. A
      small majority of the studies found positive associations with the different
      executive functions, although the associations were mostly non-significant. Given
      the scarcity of studies and the use of heterogeneous populations, tests and
      statistical analyses, no robust conclusions can be drawn at this stage.
      Therefore, caution is needed when claiming a positive association between the
      interpersonal-affective features of psychopathy and executive functioning.
      Clearly more research is needed to further validate and specify the suggested
      association. 

PMID- 24140252
TI  - Exercise affects symptom severity but not biological measures in depression and
      somatization - results on IL-6, neopterin, tryptophan, kynurenine and 5-HIAA.
AB  - Exercise leads to symptom reduction in affective disorders and functional somatic
      syndromes. Biological hypotheses of underlying mechanisms include serotonergic
      and immunological pathways. We aimed to investigate biological features in
      persons with major depression and somatoform syndromes, and to analyze effects of
      short-term graded exercise on these parameters. Baseline values for depressive
      and somatoform symptoms, tryptophan, kynurenine, 5-hydroxyindoleacetic acid,
      neopterin and interleukin-6 were compared with those after one week of increased
      and one week of reduced physical activity. Thirty-eight persons with major
      depression, 27 persons with a minimum of 6-8 somatoform symptoms, and 48 healthy
      controls participated in the study. Depressive and somatoform symptoms were
      reduced after the active week, and an interaction pointed towards group-specific
      reduction of psychopathology. Participants with major depression had lower levels
      of kynurenine compared to controls, with intermediate concentrations in
      somatoform patients. There were no systematic associations of symptom improvement
      with biological changes. A possible limitation of the design is that a control
      condition with low physical activity, but no placebo condition was included.
      People with multiple somatoform symptoms and major depression benefit from a
      short and low-graded exercise intervention. These effects do not seem to be
      mediated by changes in serotonergic and inflammatory parameters. 

PMID- 24140253
TI  - Skin conductance rises in preparation and recovery to psychosocial stress and its
      relationship with impulsivity and testosterone in intimate partner violence
      perpetrators.
AB  - Intimate partner violence (IPV) perpetrators were categorized into 2 groups using
      Gottman et al.'s (1995) typology depending on their skin conductance (SC)
      reactivity to stress. Overall, type I perpetrators tend to show autonomic
      underarousal, whereas type II perpetrators present a preparatory hyperreactivity
      to confront stress. Moreover, impulsivity traits and testosterone (T) levels may
      modulate SC responses to increase the risk of proneness to violence. In this
      study, SC response to stress was assessed by comparing IPV perpetrators with non
      violent controls while performing a modified version of the Trier Social Stress
      Test (TSST). Subjects with a history of IPV demonstrated higher non-specific SC
      responses during the recovery period than the non-violent controls. Nonetheless,
      there were no differences between groups in the case of mean SC levels.
      Furthermore, impulsivity and baseline T levels were associated with higher SC
      level reactivity during a preparation period only in IPV perpetrators, with both
      relationships being mediated by anger expression. Our results confirm that the
      IPV perpetrators correspond physiologically to type II and support the validity
      of SC as a diagnostic indicator for IPV classification. Our findings contribute
      to the development of effective treatment and prevention programs that could
      benefit from the use of biological indicators for analyzing the risk of
      recidivism in IPV perpetrators. 

PMID- 24140254
TI  - Adsorption of cations onto positively charged surface mesopores.
AB  - Uwe Neue developed a theoretical treatment to account for the adsorption of ions
      on mesopores of packing materials the walls of which are bonded to ionic ligands
      but left this work unfinished. We elaborated upon this treatment and refined it,
      based on the equivalence that he suggested between charged surface particles and
      a membrane that separates two ionic solutions but is impermeable to one
      specification. He had written that the electro-chemical potentials in both ionic
      solutions are equal (Donnan equilibrium). The equilibrium between the surface and
      the pore concentrations is accounted for by an homogeneous electrostatically
      modified Langmuir (EML) isotherm model. The theoretical results are presented for
      four different charge surface concentrations sigma0=0, 0.001, 0.002, and
      0.003C/m(2), using a phosphate buffer (W(S)pH=2.65) of ionic strength I=10mM. The
      average pore size, the specific surface area, and the specific pore volume of the
      stationary phase were Dp=140A, Sp=182m(2)/g, and Vp=0.70cm(3)/g, respectively.
      The theoretical results provide the quantitative difference between the ionic
      strength, the pH, and the concentrations of all the ions in the pores and in the
      bulk eluent. The theory predicts (1) that the retention times of cations under
      linear conditions is lower and (2) that their band widths under overloaded
      conditions for a given retention factor shrinks when the surface charge density
      sigma0 is increased. These theoretical results are in good agreement with
      experimental results published previously and explain them. 

PMID- 24140255
TI  - Effect of pressure on secondary structure of proteins under ultra high pressure
      liquid chromatographic conditions.
AB  - There are several spectroscopic techniques such as IR and CD, that allow for
      analyzing protein secondary structure in solution. However, a majority of these
      techniques require using purified protein, concentrated enough in the solution,
      to produce a relevant spectrum. Fundamental principles for the usage of reversed
      phase ultra high pressure liquid chromatography (UHPLC) as an alternative
      technique to study protein secondary structures in solution were investigated.
      Several "model" proteins, as well as several small ionizable and neutral
      molecules, were used for these studies. The studies were conducted with UHPLC in
      isocratic mode, using premixed mobile phases at constant flow rate and
      temperature. The pressure was modified by a backpressure regulator from about
      6000psi to about 12,000psi. It was found that when using a mobile phase
      composition at which proteins were fully denatured (loss of alpha-helix secondary
      structure), the retention factors of the proteins increased upon pressure
      increase in the same manner as non-proteins. When using a mobile phase
      composition in which proteins were not fully denatured, it was observed that the
      retention factors of the proteins displayed a much steeper (by one order of
      magnitude) increase in retention upon pressure increase. It was concluded that in
      a mobile phase in which the protein is not initially fully denatured, the
      increase of pressure may facilitate the folding back of the protein to its native
      state (alpha-helix secondary structure). The impact of different mobile phase
      compositions on the denaturation of the proteins was studied using CD (Circular
      Dichroism). Moreover, the effect of flow rate on retention of proteins and small
      molecules was studied at constant pressure on the different pore size silicas and
      the impact of internal frictional heating was evaluated. 

PMID- 24140256
TI  - Enteroendocrine cell types revisited.
AB  - The GI-tract is profoundly involved in the control of metabolism through peptide
      hormones secreted from enteroendocrine cells scattered throughout the gut mucosa.
      A large number of recently generated transgenic reporter mice have allowed for
      direct characterization of biochemical and cell biological properties of these
      previously highly elusive enteroendocrine cells. In particular the surprisingly
      broad co-expression of six functionally related hormones in the intestinal
      enteroendocrine cells indicates that it should be possible to control not only
      the hormone secretion but also the type and number of enteroendocrine cells.
      However, this will require a more deep understanding of the factors controlling
      differentiation, gene expression and specification of the enteroendocrine cells
      during their weekly renewal from progenitor cells in the crypts of the mucosa. 

PMID- 24140257
TI  - Photodynamic therapy for polypoidal choroidal vasculopathy.
AB  - The first effective therapy for exudative macular degeneration (AMD) was
      Photodynamic Therapy (PDT). Diagnosis of the disease was to a large extent by
      fluorescein angiography (FA). Distinguishing between the leaky choroidal
      neovessels (CNV) associated with exudative AMD, and the polypoidal structures
      associated with Polypoidal Choroidal Vasculopathy (PCV) is not always easy using
      FA alone. The switch to Indocyanine Green angiography helped to pinpoint PCV, and
      thus to study the efficacy of photodynamic therapy of this particular form of
      retinal disease, which is more frequently encountered among pigmented
      individuals. The results appear to be quite promising, and in the year following
      treatment only a small fraction of the patients had to be retreated.
      Alternatively, treating PCV with repeated intravitreal VEGF blocking agents was
      not as successful as it was in the treatment of wet AMD. However, combining PDT
      induced angio-occlusion of the polypoidal lesions with anti-vascular endothelial
      growth factor therapy was shown to be quite effective, and the combination of PDT
      with an anti-angiogenic agent as well as a steroid, in a triple therapy, was
      recently also shown to be a quite promising option. In the present article we
      review the data on PDT of PCV, including combination therapies and alternative
      treatments. We also report on similarities and differences between AMD and PCV. 

PMID- 24140258
TI  - Gastric bypass surgery in women with or without polycystic ovary syndrome--a
      comparative observational cohort analysis.

PMID- 24140259
TI  - In-hospital mortality of acutely ill medical patients admitted to a resource poor
      hospital in sub-Saharan Africa and to a Canadian regional hospital compared using
      the abbreviated VitalPAC Early Warning Score.
AB  - BACKGROUND: the development of validated early warning scores that only require
      the measurement of vital signs at the bedside has provided for the first time a
      practical and affordable method of comparing the outcomes of similar patients
      admitted to hospital in the developed and developing world. METHODS: we compared
      the outcomes of patients with the same abbreviated version of the VitalPAC early
      warning score at the time of hospital admission in a Canadian and Ugandan
      hospital. 844 acutely ill medical patients admitted to Kitovu Hospital, Masaka,
      Uganda and 48,696 patients admitted to the Thunder Bay Regional Health Sciences
      Centre (TBRHSC), Ontario, Canada were examined. RESULTS: apart from those
      patients with an abbreviated ViEWS value of 10 there was no statistically
      significant difference in the in-hospital mortality of Kitvou and TBRHSC patients
      with the same score on admission. Using arbitrary ranges of the abbreviated ViEWS
      the 30day Kaplan-Meier survival curves of Kitovu patients were either the same or
      better than those of TBRHSC patients. CONCLUSION: the in-hospital mortality of
      patients with the same abbreviated ViEWS on hospital admission is similar in
      TBRHSC and Kitovu Hospital.

PMID- 24140260
TI  - [Is subjective well-being perceived by non-health care workers different from
      that perceived by nurses? Relation with personality and resilience].
AB  - Subjective well-being (SWB), usually called 'happiness', is influenced directly
      by psychological factors. Personality and resilience (capacity of recover from
      adversity) are included among these factors. Empirical evidence has demonstrated
      that resilience is an essential and inherent characteristic for the nursery
      staff. This study has aimed to analyze personality factors (including resilience)
      related with SWB (satisfaction with life, positive and negative affect) in a
      nursery staff sample (n=59) of intensive care and cardiological units, and a non
      health care workers sample (n=50) mainly made up of government employees and
      teachers. Multiple regression analyses showed that SWB was associated with more
      resilience and less neuroticism in the nursery staff. Extraversion and
      conscientiousness (positively related), and neuroticism (negatively related) were
      the significant predictors of SWB in the non-health care workers group. Finally,
      mediational analyses revealed that resilience measured the relationships between
      extraversion (total mediation) and neuroticism (partial mediation) with SWB in
      the nursery staff group, but not in the group of non-health care workers. The
      results show the importance of resilience for nursery staff of intensive care
      units, since they are constantly exposed to human suffering and to a continually
      adverse occupational environment. Likewise, the discussion stresses that
      resilience is a means for nursing staff to cope with the occupational stress and
      that resilient nurses are a crucial element in our health care system. 

PMID- 24140261
TI  - Identification and characterization of transforming growth factor beta induced
      gene (TGFBIG) from Branchiostoma belcheri: insights into evolution of TGFBI
      family.
AB  - The transforming growth factor beta induced gene (TGFBIG) encodes a protein
      (TGFBI) which plays important roles in many biological processes. However, no
      TGFBIG homolog has been reported in B. belcheri. Here, we identified a TGFBI-like
      gene from B. belcheri and extensively studied the evolutionary history of TGFBI
      family. We found that the amphioxus genome contains a TGFBIG homolog designated
      as AmphiTGFBI which encodes a protein with 5 Fas1 domains. The TGFBIGs were
      present in a common ancestor with Amphimedon queenslandica. We also demonstrated
      expression patterns of AmphiTGFBI in five amphioxus tissues. Interestingly, the
      gene structures and conserved motifs of invertebrate TGFBIGs were found to
      present regular changes in the evolution. Positive selection and Fas1 domain loss
      might cause the regular changes of gene structures and conserved motifs in
      invertebrate TGFBIGs during evolution. Together, our findings provided an insight
      into the evolution of the TGFBI family. 

PMID- 24140262
TI  - Cell fate control in the developing central nervous system.
AB  - The principal neural cell types forming the mature central nervous system (CNS)
      are now understood to be diverse. This cellular subtype diversity originates to a
      large extent from the specification of the earlier proliferating progenitor
      populations during development. Here, we review the processes governing the
      differentiation of a common neuroepithelial cell progenitor pool into mature
      neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We
      focus on studies performed in mice and involving two distinct CNS structures: the
      spinal cord and the cerebral cortex. Understanding the origin, specification and
      developmental regulators of neural cells will ultimately impact comprehension and
      treatments of neurological disorders and diseases. 

PMID- 24140263
TI  - Non-canonical functions of the peripheral nerve.
AB  - The peripheral nervous system (PNS) is complex and omnipresent. The PNS targets
      all parts of the body starting from early stages of embryonic development, and in
      large part, is derived from multipotent migratory neural crest stem cells.
      Current opinion mostly perceives the PNS as a means of communication and
      information exchange between the central nervous system, the rest of the body and
      the environment. Additionally, the PNS is largely associated with autonomic
      control. Being an "alternative brain" it provides local regulation of processes
      in organs. However, it has become evident in recent years that in addition to
      these main canonical functions the PNS possesses a number of other important
      roles in development and homeostasis of targeted tissues, for instance, in nerve
      dependent regeneration. The PNS represents a niche that hosts neural crest
      derived peripheral glial cells, or, in other words, neural crest-like multipotent
      cells throughout the entire body. These multipotent nerve-adjacent cells can be
      reprogrammed in vivo and play a number of roles from creating pigmentation to
      controlling regeneration of a limb in amphibians or skin in rodents. In the
      current review we outline newly emerged, non-canonical functions of the PNS and
      briefly describe cellular and molecular aspects of these alternative functions. 

PMID- 24140264
TI  - Emodin attenuates high glucose-induced TGF-beta1 and fibronectin expression in
      mesangial cells through inhibition of NF-kappaB pathway.
AB  - The activation of nuclear factor-kappaB (NF-kappaB) and the subsequent
      overexpression of its downstream targets transforming growth factor-beta1 (TGF
      beta1) and fibronectin (FN) are among the hallmarks for the progressive diabetic
      nephropathy. Our previous studies demonstrated that emodin ameliorated renal
      injury and inhibited extracellular matrix accumulation in kidney and mesangial
      cells under diabetic condition. However, the molecular mechanism has not been
      fully elucidated. Here, we showed that emodin significantly attenuated high
      glucose-induced NF-kappaB nuclear translocation in mesangial cells.
      Interestingly, emodin also inhibited the DNA-binding activity and transcriptional
      activity of NF-kappaB. Furthermore, NF-kappaB-mediated TGF-beta1 and FN
      expression was significantly decreased by emodin. These results demonstrated that
      emodin suppressed TGF-beta1 and FN overexpression through inhibition of NF-kappaB
      activation, suggesting that emodin-mediated inhibition of the NF-kappaB pathway
      could protect against diabetic nephropathy. 

PMID- 24140265
TI  - Pathogenetic differences after experimental infection of calves with Korean non
      cytopathic BVDV-1 and BVDV-2 isolates.
AB  - The purpose of this study was to compare clinical and virological differences
      between non-cytopathic (ncp) bovine viral diarrhea virus (BVDV)-1 and ncp BVDV-2
      isolated from Korean field cases. Each five naive calves were experimentally
      infected with Korean ncp BVDV-1 or BVDV-2 isolates. Two additional age-matched
      animals were used as uninfected controls. Leukocyte, lymphocyte, and platelet
      counts declined in all infected calves, but were significantly lower and remained
      decreased longer in calves infected with ncp BVDV-2 isolate. The number of
      monocytes was greater in calves infected with ncp BVDV-2. Flow cytometric assay
      showed that lymphocyte apoptosis occurred with an increase of annexin-V positive
      cells in all infected calves by day 6. Tumor necrosis factor alpha (TNF-alpha)
      concentration in all infected calves was lower than in control calves. In ncp
      BVDV-1 infected calves, interferon gamma (IFN-gamma) levels in the serum were
      increased by day 6 compared to calves infected with ncp BVDV-2. These results
      demonstrated that the Korean ncp BVDV-2 isolate shows a reduced IFN-gamma
      production, indicating prevention of the antiviral activity, and therefore
      promotes the development of pathological effects. 

PMID- 24140266
TI  - Taking a risk: a therapeutic focus on ataxin-2 in amyotrophic lateral sclerosis?
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused
      by the loss of lower and upper motor neurons leading to progressive muscle
      weakness and respiratory insufficiency. No treatment is currently available to
      cure ALS. Recent progress has led to the identification of several novel genetic
      determinants of this disease, including repeat expansions in the ataxin-2 (ATXN2)
      gene. Ataxin-2 is mislocalized in ALS patients and represents a relatively common
      susceptibility gene in ALS, making it a promising therapeutic target. In this
      review, we summarize genetic and pathological data implicating ataxin-2 in ALS,
      discuss potential disease mechanisms linked to altered ataxin-2 localization or
      function, and propose potential strategies for therapeutic intervention in ALS
      based on ataxin-2. 

PMID- 24140267
TI  - The Muscle Sensor for on-site neuroscience lectures to pave the way for a better
      understanding of brain-machine-interface research.
AB  - Neuroscience is an expanding field of science to investigate enigmas of brain and
      human body function. However, the majority of the public have never had the
      chance to learn the basics of neuroscience and new knowledge from advanced
      neuroscience research through hands-on experience. Here, we report that we
      produced the Muscle Sensor, a simplified electromyography, to promote educational
      understanding in neuroscience. The Muscle Sensor can detect myoelectric
      potentials which are filtered and processed as 3-V pulse signals to shine a light
      bulb and emit beep sounds. With this educational tool, we delivered "On-Site
      Neuroscience Lectures" in Japanese junior-high schools to facilitate hands-on
      experience of neuroscientific electrophysiology and to connect their text-book
      knowledge to advanced neuroscience researches. On-site neuroscience lectures with
      the Muscle Sensor pave the way for a better understanding of the basics of
      neuroscience and the latest topics such as how brain-machine-interface technology
      could help patients with disabilities such as spinal cord injuries. 

PMID- 24140268
TI  - Aflibercept versus placebo in combination with fluorouracil, leucovorin and
      irinotecan in the treatment of previously treated metastatic colorectal cancer:
      prespecified subgroup analyses from the VELOUR trial.
AB  - PURPOSE: The antiangiogenic agent aflibercept (ziv-aflibercept in the United
      States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI)
      significantly improved survival in a phase III study of patients with metastatic
      colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In
      the present analysis, outcomes were evaluated in prespecified subgroups to assess
      the consistency of the treatment effect. METHODS: Patients were randomised to
      receive FOLFIRI plus aflibercept or placebo every 2weeks until disease
      progression or unacceptable toxicity occurred. Efficacy and safety outcomes were
      analysed with respect to demographic and baseline characteristics, and
      stratification factors (prior bevacizumab treatment and Eastern Cooperative
      Oncology Group performance status). RESULTS: Median overall survival (OS, months
      [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8
      15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and
      13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab
      treatment. The p value for interaction was 0.5668, indicating there was no
      heterogeneity in these subgroups. For OS and progression-free survival (PFS),
      there was a significantly greater benefit (at the 2-sided 10% level) of treatment
      for patients with liver only metastases versus patients with no liver
      metastases/liver metastases with other organ involvement (p value for
      interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity
      in treatment effect in any of the other subgroups examined. CONCLUSIONS: The
      benefits of aflibercept in combination with FOLFIRI in patients with mCRC
      previously treated with oxaliplatin were maintained across the specified patient
      subgroups, including in patients with or without prior bevacizumab treatment.

PMID- 24140270
TI  - The battle against infection is as old as human civilization. Foreword.

PMID- 24140269
TI  - Inhibition of 17alpha-hydroxylase/C17,20 lyase reduces gating deficits consequent
      to dopaminergic activation.
AB  - Cogent evidence points to the involvement of neurosteroids in the regulation of
      dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of
      this link remain poorly understood. We previously showed that inhibition of
      5alpha-reductase (5alphaR), a key neurosteroidogenic enzyme, attenuates the
      sensorimotor gating deficits induced by DA receptor activation, as measured by
      the prepulse inhibition (PPI) of the acoustic startle reflex. To extend these
      findings, the present study was aimed at the assessment of the role of other key
      neurosteroidogenic enzymes in PPI, such as 17alpha-hydroxylase/C17,20 lyase
      (CYP17A1), 3alpha- and 3beta-hydroxysteroid dehydrogenase (HSD), in Sprague
      Dawley rats. The PPI deficits induced by the DAergic non-selective agonist
      apomorphine (APO, 0.25mg/kg, SC) were dose-dependently attenuated by the
      selective CYP17A1 inhibitor abiraterone (ABI, 10-50mg/kg, IP) in a fashion akin
      to that of the 5alphaR inhibitor finasteride (FIN, 100mg/kg, IP). These systemic
      effects were reproduced by intracerebroventricular injection of ABI (1 MUg/1
      MUl), suggesting the involvement of brain CYP17A1 in PPI regulation. Conversely,
      the PPI disruption induced by APO was not significantly affected by the 3alpha-
      and 3beta-HSD inhibitors indomethacin and trilostane. Given that CYP17A1
      catalyzes androgen synthesis, we also tested the impact on PPI of the androgen
      receptor (AR) antagonist flutamide (10mg/kg, IP). However, this agent failed to
      reverse APO-induced PPI deficits; furthermore, AR endogenous ligands testosterone
      and dihydrotestosterone failed to disrupt PPI. Collectively, these data highlight
      CYP17A1 as a novel target for antipsychotic-like action, and suggest that the
      DAergic regulation of PPI is modulated by androgenic neurosteroids, through AR
      unrelated mechanisms.

PMID- 24140271
TI  - The economic impact of periprosthetic infections following total knee
      arthroplasty at a specialized tertiary-care center.
AB  - The purpose of this study was to measure the impact of periprosthetic joint
      infections (PJIs) on the length of hospitalization, readmissions, and the
      associated costs. Between 2007 and 2011, our prospectively collected infection
      database was reviewed to identify PJIs that occurred following primary total knee
      arthroplasty (TKA), which required a two-stage revision. We identified 21
      consecutive patients and matched them to 21 non-infected patients who underwent
      uncomplicated primary TKA. The patients who had PJIs had significantly longer
      hospitalizations (5.3 vs. 3.0 days), more readmissions (3.6 vs. 0.1), and more
      clinic visits (6.5 vs. 1.3) when compared to the matched group, respectively. The
      mean annual cost was significantly higher in the infected cohort ($116,383;
      range, $44,416 to $269,914) when compared to the matched group ($28,249; range,
      $20,454 to $47,957). Periprosthetic infections following TKA represent a
      tremendous economic burden for tertiary-care centers and to patients.

PMID- 24140273
TI  - Executive summary.

PMID- 24140274
TI  - Imageless computer navigation in total knee arthroplasty provides superior short
      term functional outcomes: a meta-analysis.
AB  - Computer navigation in total knee arthroplasty (TKA) is intended to produce more
      reliable results, but its impact on functional outcomes has not been firmly
      demonstrated. Literature searches were performed for Level I randomized trials
      that compared TKA using imageless computer navigation to those performed with
      conventional instruments. Radiographic and functional outcomes were extracted and
      statistically analyzed. TKA performed with computer navigation was more likely to
      be within 3 degrees  of ideal mechanical alignment (87.1% vs. 73.7%, P < .01).
      Navigated TKAs had a higher increase in Knee Society Score at 3-month follow-up
      (68.5 vs. 58.1, P = .03) and at 12-32 month follow-up (53.1 vs. 45.8, P < .01).
      Computer navigation in TKA provides more accurate alignment and superior
      functional outcomes at short-term follow-up.

PMID- 24140275
TI  - Converting between high- and low-sensitivity C-reactive protein in the assessment
      of periprosthetic joint infection.
AB  - Although low-sensitivity CRP (Ls-CRP) is an important tool for evaluating
      infected orthopedic prostheses, no clinical studies have evaluated whether Hs-CRP
      is a suitable surrogate for Ls-CRP or other traditional infection biomarkers. The
      laboratory data of 98 arthroplasty patients with suspected prosthetic infection
      were reviewed. Hs-CRP was highly correlated with Ls-CRP (R = 0.93). ROC analysis
      generated 100% sensitivity and 97% specificity for both Hs-CRP and Ls-CRP at
      optimal cutoffs of 28.6 and 2.6 mg/dL, respectively. Both CRP tests were more
      accurate than serum erythrocyte sedimentation rate, neutrophil differential, and
      white blood cell count. Hs-CRP was no different from Ls-CRP after unit
      conversion, and regression analyses suggested conversion factors that
      approximated 10. Hs-CRP and Ls-CRP have equivalent utility in the diagnosis of
      infected joint arthroplasty.

PMID- 24140276
TI  - Are gender-specific femoral implants for total knee arthroplasty necessary?
AB  - The purpose of this study was to determine the effect of gender on epiphyseal
      morphology and using this information to determine if an implant product line
      with a single width provides sufficient bone coverage for the entire population
      of knees being replaced. Morphology of the distal femoral epiphysis from 420
      continuous knees was acquired with a surgical navigation system during primary
      TKA. A three-dimensional model of the distal femur was generated and used to
      determine the anterioposterior (AP) and mediolateral (ML) dimensions on 19
      different virtual knee sections. Female knees had smaller AP and ML dimensions
      than male knees. The ML width of the distal femoral epiphysis was associated with
      femur length, not gender. Measurements derived from surgical navigation confirm
      that distal femoral epiphysis dimensions are related to femur length only
      independently of gender. 

PMID- 24140277
TI  - Our midterm results of the Birmingham hip resurfacing with and without
      navigation.
AB  - We reviewed 148 consecutive hip resurfacings in order to assess the clinical
      outcomes of the BHR at midterm follow-up and to compare the accuracy of the
      navigation in the positioning of femoral component. We retrospectively analyzed
      85 hips using the conventional jig to implant the femoral component and we
      prospectively followed 63 hips operated on by navigation. At a mean follow-up of
      50.54 months, the Harris hip score improved significantly from 44.66
      preoperatively to 98.45 postoperatively without any differences between the
      groups. Radiologically, we classic navigated group. Our clinical outcomes are
      excellent at midterm follow-up and the navigation definitely improves the implant
      position in both planes.

PMID- 24140279
TI  - Methylation of the DNA/RNA-binding protein Kin17 by METTL22 affects its
      association with chromatin.
AB  - Kin17 is a protein that was discovered through its immunoreactivity towards an
      antibody directed against prokaryotic RecA. Further study of Kin17 revealed a
      function in DNA replication and repair, as well as in pre-mRNA processing.
      Recently, it was found that Kin17 is methylated on lysine 135 by the newly
      discovered methyltransferase METTL22. To better understand the function of Kin17
      and its regulation by methylation, we used multiple cell compartment protein
      affinity purification coupled with mass spectrometry (MCC-AP-MS) to identify
      novel interaction partners of Kin17 and to assess whether these interactions can
      take place on chromatin. Our results confirm that Kin17 interacts with METTL22
      both in the soluble and chromatin fractions. We also show that many RNA-binding
      proteins, including the previously identified interactor BUD13 as well as
      spliceosomal and ribosomal subunits, associate with Kin17 in the soluble
      fraction. Interestingly, overexpression of METTL22 in HEK 293 cells displaces
      Kin17 from the chromatin to the cytoplasmic fraction, suggesting a role for
      methylation of lysine 135, a residue that lies within a winged helix domain of
      Kin17, in regulating association with chromatin. These results are discussed in
      view of the putative cellular function of Kin17. BIOLOGICAL SIGNIFICANCE: The
      results shown here broaden our understanding of METTL22, a member of a family of
      newly-discovered non-histone lysine methyltransferases and its substrate, Kin17,
      a DNA/RNA-binding protein with reported roles in DNA repair and replication and
      mRNA processing. An innovative method to study protein-protein interactions in
      multiple cell compartments is employed to outline the interaction network of both
      proteins. Functional experiments uncover a correlative role between Kin17 lysine
      methylation and its association with chromatin. This article is part of a Special
      Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

PMID- 24140280
TI  - Proteomics discovery of biomarkers for mitral regurgitation caused by mitral
      valve prolapse.
AB  - Mitral regurgitation (MR) is a common valvular lesion frequently caused by mitral
      valve prolapse (MVP). Surgical intervention in MVP patients with significant MR
      is predicated on symptoms and measures of left ventricular dysfunction. Because
      these indicators may be subjective or imprecise, serological biomarkers of
      disease could be a valuable adjunct to standard evaluation. This study aimed to
      identify such biomarkers by a proteomics approach. Two pooled plasma samples from
      24 MVP subjects with MR (MVP/MR) and 24 non-MVP individuals were treated with the
      combinatorial peptide ligand library (CPLL) beads prior to iTRAQ labeling and ESI
      MS/MS. Lower levels of haptoglobin, platelet basic protein (PBP), and complement
      component C4b were observed in the MVP/MR as compared to the control sample.
      These findings were verified by ELISA testing of each of the 24 paired samples,
      and another 42 matched cases and controls. The AUC values, sensitivities and
      specificities for (i) haptoglobin, (ii) PBP, (iii) C4b, and (iv) all 3 proteins
      in combination were (i) 0.813, 76%, 74%; (ii) 0.721, 56%, 77%; (iii) 0.689, 83%,
      49%; and (iv) 0.840, 89%, 67%, respectively. In conclusion, haptoglobin, PBP, and
      C4b are down-regulated in MVP/MR. Their value as serological biomarkers of
      valvular pathology should be further explored. BIOLOGICAL SIGNIFICANCE: We report
      the first study that performed comparative proteomics of clinical human plasma
      samples to identify novel diagnostic biomarkers for mitral valve prolapse (MVP)
      patients with moderate to severe mitral regurgitation (MR). MR is a common
      valvular lesion that can be complicated by heart failure, sudden death and atrial
      fibrillation, yet many patients with severe MR are asymptomatic. Our results
      revealed reduced levels of haptoglobin, platelet basic protein (PBP), and
      complement component C4b in the MVP/MR patients as compared to the matched
      control cases. The plasma proteomics findings were subsequently confirmed by
      ELISA. Each of these candidate biomarkers has a putative role in the
      pathophysiology of MVP/MR, further supporting their roles in detection and
      possibly surveillance and prognostication of this disease.

PMID- 24140281
TI  - [Insomnia and total sleep time in France: prevalence and associated socio
      demographic factors in a general population survey].
AB  - INTRODUCTION: Sleep is considered as a major protective factor for good health
      and quality of life. The epidemiology of chronic insomnia and other sleep
      disorders has recently been developed in France. The aim of this study was to
      evaluate total sleep time and the prevalence of chronic insomnia in the general
      population aged 15 to 85 years. It was also to investigate factors associated
      with sleep disorders. METHODS: Within the framework of the Health Barometer 2010,
      a French general population survey, 27,653 15 to 85-year-old individuals were
      questioned about their health behaviors and attitudes, in particular about their
      sleeping time and habits. RESULTS: The average sleeping time of the 15 to 85-year
      old was 7 hours 13 minutes. It was higher for women than for men (7 hours 18
      minutes vs 7 hours 07 minutes; P<0.001), whereas 15.8 % of the population
      presented criteria for chronic insomnia, 19.3 % of women and 11.9 % of men
      (P<0.001). The prevalence of chronic insomnia was stable with age among women,
      around 19 %, whereas it increased for men from 3 % in the 15-19-year age range to
      18 % in the 45-54-year age range, before decreasing to 8 % beyond 65 years.
      Chronic insomnia was also found to be related to precarious situations and to
      several difficult events of life such as violence or chronic alcohol abuse,
      whereas the relationship observed with tobacco smoking was no longer found after
      logistic regression adjustment for socio-demographic characteristics. Since the
      beginning of 1990s, a single-question inquiry on "sleeping problems present
      during the last 8 days" has been asked in the Health Barometer. The rate of
      subjects concerned increased from 1995, with a prevalence stabilized at a high
      level since 2000. CONCLUSIONS: Based on these data, we think that the
      surveillance of sleep disorders is an important public health issue and that
      prevention and health educational initiatives should be launched in the general
      population to promote a better quality of sleep.

PMID- 24140282
TI  - [Status epilepticus revealing Kikuchi-Fujimoto disease: a case report and review
      of the literature].

PMID- 24140283
TI  - 'All the better for not seeing you': effects of communicative context on the
      speech of an individual with acquired communication difficulties.
AB  - Evidence shows that speakers adjust their speech depending on the demands of the
      listener. However, it is unclear whether people with acquired communication
      disorders can and do make similar adaptations. This study investigated the impact
      of different conversational settings on the intelligibility of a speaker with
      acquired communication difficulties. Twenty-eight assessors listened to
      recordings of the speaker reading aloud 40 words and 32 sentences to a listener
      who was either face-to-face or unseen. The speaker's ability to convey
      information was measured by the accuracy of assessors' orthographic
      transcriptions of the words and sentences. Assessors' scores were significantly
      higher in the unseen condition for the single word task particularly if they had
      heard the face-to-face condition first. Scores for the sentence task were
      significantly higher in the second presentation regardless of the condition. The
      results from this study suggest that therapy conducted in situations where the
      client is not able to see their conversation partner may encourage them to
      perform at a higher level and increase the clarity of their speech. LEARNING
      OUTCOMES: Readers will be able to describe: (1) the range of conversational
      adjustments made by speakers without communication difficulties; (2) differences
      between these tasks in offering contextual information to the listener; and (3)
      the potential for using challenging communicative situations to improve the
      performance of adults with communication disorders.

PMID- 24140284
TI  - Impacts of globalisation on foodborne parasites.
AB  - Globalisation is a manmade phenomenon encompassing the spread and movement of
      everything, animate and inanimate, material and intangible, around the planet.
      The intentions of globalisation may be worthy--but may also have unintended
      consequences. Pathogens may also be spread, enabling their establishment in new
      niches and exposing new human and animal populations to infection. The plethora
      of foodborne parasites that could be distributed by globalisation has only
      recently been acknowledged and will provide challenges for clinicians,
      veterinarians, diagnosticians, and everyone concerned with food safety.
      Globalisation may also provide the resources to overcome some of these
      challenges. It will facilitate sharing of methods and approaches, and
      establishment of systems and databases that enable control of parasites entering
      the global food chain.

PMID- 24140285
TI  - Are we missing opportunities to confirm the diagnosis of tuberculosis by
      microbial culture?
AB  - SETTING: Tuberculosis (TB) incidence is rising globally, with drug resistance
      becoming increasingly problematic. Microbiological confirmation ensures correct
      anti-tuberculous chemotherapy. OBJECTIVE/DESIGN: We retrospectively analysed all
      TB cases diagnosed in Central Manchester in 2009 investigating how often we are
      not achieving microbiological diagnosis, factors influencing this and whether
      opportunities to obtain microbiological samples are missed. RESULTS: 128/156
      (82%) cases had samples sent for microbiology. Factors affecting this included
      disease site, with ocular disease least likely to be sampled (p < 0.0001), and
      patient age (with children less likely to be sampled p = 0.002). Ethnicity did
      not affect sampling (n.s.). Overall, 92/156 (59%) cases were culture positive.
      Negative culture was related to specimen type (p < 0.0001) and patient age (p =
      0.019), with children significantly less likely to have a positive culture.
      Ethnicity and disease site did not affect culture results. There was a trend
      towards culture positivity being more common in pulmonary (75%) than non
      pulmonary (46%) disease (n.s.). In only 7 (4%), could samples have been sent
      where they were originally absent (3) or further samples obtained where the
      cultures proved to be negative (4). CONCLUSION: Despite an overall culture
      positive rate of 59%, opportunities to achieve microbiological confirmation are
      seldom missed. In our centre, which is typical of UK practice, this lack of
      capacity to increase microbiological confirmation, particularly in an era of
      increasing importance of extra-pulmonary TB, is concerning. Improvements in
      sample acquisition and laboratory methods are urgently required.

PMID- 24140286
TI  - Re: a novel technique for harvesting autologous fat prior its transfer.

PMID- 24140287
TI  - Drug name recognition in biomedical texts: a machine-learning-based method.
AB  - Currently, there is an urgent need to develop a technology for extracting drug
      information automatically from biomedical texts, and drug name recognition is an
      essential prerequisite for extracting drug information. This article presents a
      machine-learning-based approach to recognize drug names in biomedical texts. In
      this approach, a drug name dictionary is first constructed with the external
      resource of DrugBank and PubMed. Then a semi-supervised learning method, feature
      coupling generalization, is used to filter this dictionary. Finally, the
      dictionary look-up and the condition random field method are combined to
      recognize drug names. Experimental results show that our approach achieves an F
      score of 92.54% on the test set of DDIExtraction2011. 

PMID- 24140288
TI  - Glutaminase regulation in cancer cells: a druggable chain of events.
AB  - Metabolism is the process by which cells convert relatively simple extracellular
      nutrients into energy and building blocks necessary for their growth and
      survival. In cancer cells, metabolism is dramatically altered compared with
      normal cells. These alterations are known as the Warburg effect. One consequence
      of these changes is cellular addiction to glutamine. Because of this, in recent
      years the enzyme glutaminase has become a key target for small molecule
      therapeutic intervention. Like many oncotargets, however, glutaminase has a
      number of upstream partners that might offer additional druggable targets. This
      review summarizes the work from the current decade surrounding glutaminase and
      its regulation, and suggests strategies for therapeutic intervention in relevant
      cases. 

PMID- 24140289
TI  - Oncocytic meningioma: a case report and review of the literature.
AB  - Oncocytic meningioma is an uncommon variant of meningioma, with only 20 reported
      cases to date, that is histologically characterized by the presence of neoplastic
      cells with granular eosinophilic cytoplasm rich in mitochondria. We present the
      clinicopathological features of a case of oncocytic meningioma in a 49-year-old
      Chinese female, along with a literature review. Brain computed tomography and
      magnetic resonance imaging demonstrated a slightly hyperintense mass located in
      the right frontal region and attached to the dura. In addition, it was
      homogeneously enhanced following contrast administration. She underwent gross
      total surgical resection of the tumor and adjacent dura. Grossly, the well
      demarcated, nonencapsulated mass had a solid and tan-white appearance with soft
      and rubbery consistency. The lesions were composed primarily of sheets, nests,
      and cords of large polygonal bland cells with finely granular eosinophilic
      cytoplasm rich in mitochondria. Mitotic figures were rare, and necrosis was
      absent. There was no infiltration of the dura or brain cortex.
      Immunohistochemical staining revealed that the neoplastic cells were positive for
      vimentin, epithelial membrane antigen, antimitochondrial antibody, and
      progesterone receptor, whereas MIB-1 stained only approximately 1% of the tumor
      cells. This is the first known report of an oncocytic meningioma arising in a
      Chinese patient. The patient was followed for 19 months without any evidence of
      metastasis or recurrence. 

PMID- 24140290
TI  - Impact of different CO2/HCO3- levels on metabolism and regulation in
      Corynebacterium glutamicum.
AB  - We investigated the growth kinetics and transcriptional responses of
      Corynebacterium glutamicum in environments with low (pCO2<40 mbar) and high (pCO2
      >= 300 mbar) CO2/HCO3(-) levels compared to standard conditions. When cultivated
      at high CO2/HCO3(-)-levels, C. glutamicum showed increased (63%) biomass to
      substrate yields during the initial growth phase. Other kinetic parameters such
      as growth rate (MU), specific glucose consumption rate (qS), and selected
      enzymatic activities of anaplerotic reactions, the pentose phosphate pathway and
      the tricarboxylic acid cycle were similar to standard conditions. However,
      microarray hybridization disclosed a complex transcriptional response involving
      117 differentially expressed genes. Among those, 60 genes were assigned to the
      complete DtxR/RipA regulon controlling iron homeostasis in C. glutamicum.
      Impaired growth of a DeltadtxR mutant at high CO2/HCO3(-) levels validated the
      relevance of this master regulator to cope with excessive CO2/HCO3(-)
      availability. At low CO2/HCO3(-) levels, C. glutamicum grew in a bi-level manner
      with three distinct growth phases. Differential analyses revealed approximately
      doubled activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase accompanied by the formation of L-alanine and L-valine during the
      lowest MU occurring in mid-phase of the cultivation. DNA microarray analysis
      revealed more than 100 differentially expressed genes in growth phase II compared
      to phase I including almost all thiamin pyrophosphate (TPP) biosynthesis genes,
      which were significantly up regulated. Concluding, we hypothesize that C.
      glutamicum counteracts the lack of CO2/HCO3(-) by triggering TPP biosynthesis for
      increasing the activities of TPP-dependent enzymes involved in CO2 formation.

PMID- 24140291
TI  - Complete genome sequence of the kirromycin producer Streptomyces collinus Tu 365
      consisting of a linear chromosome and two linear plasmids.
AB  - Streptomyces collinus Tu 365 (DSMZ 40733), isolated from Kouroussa (Guinea), is
      the producer of the elfamycin family antibiotic kirromycin, which inhibits
      bacterial protein biosynthesis by interfering with elongation factor EF-Tu. Here,
      we report on the Streptomyces collinus Tu 365 complete genome sequence of the
      8.27 MB chromosome and the two plasmids SCO1 and SCO2.

PMID- 24140292
TI  - Insights from the draft genome of Paenibacillus lentimorbus NRRL B-30488, a
      promising plant growth promoting bacterium.
AB  - Paenibacillus lentimorbus NRRL B-30488, a plant growth-promoting bacterium was
      isolated from Sahiwal cow's milk. The strain shows antagonism against
      phytopathogens, Fusarium oxysporum f. sp. ciceri and Alternaria solani. Its
      genome contains gene clusters involved in nonribosomal synthesis of secondary
      metabolites involved in antimicrobial activities. The genome sequence of P.
      lentimorbus NRRL B-30488 provides the genetic basis for application of this
      bacterial strain in plant growth promotion, plant protection and degradation of
      organic pollutants. 

PMID- 24140293
TI  - E. coli sabotages the in vivo production of O-linked beta-N-acetylglucosamine
      modified proteins.
AB  - The O-linked beta-N-acetylglucosamine (O-GlcNAc) post-translational modification
      is an important, regulatory modification of cytosolic and nuclear enzymes. To
      date, no 3-dimensional structures of O-GlcNAc-modified proteins exist due to
      difficulties in producing sufficient quantities with either in vitro or in vivo
      techniques. Recombinant co-expression of substrate protein and O-GlcNAc
      transferase in Escherichia coli was used to produce O-GlcNAc-modified domains of
      human cAMP responsive element-binding protein (CREB1) and Abelson tyrosine-kinase
      2 (ABL2). Recombinant expression in E. coli is an advantageous approach, but only
      small quantities of insoluble O-GlcNAc-modified protein were produced. Adding
      beta-N-acetylglucosaminidase inhibitor, O-(2-acetamido-2-dexoy-D
      glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), to the culture media
      provided the first evidence that an E. coli enzyme cleaves O-GlcNAc from proteins
      in vivo. With the inhibitor present, the yields of O-GlcNAc-modified protein
      increased. The E. coli beta-N-acetylglucosaminidase was isolated and shown to
      cleave O-GlcNAc from a synthetic O-GlcNAc-peptide in vitro. The identity of the
      interfering beta-N-acetylglucosaminidase was confirmed by testing a nagZ knockout
      strain. In E. coli, NagZ natively cleaves the GlcNAc-beta1,4-N-acetylmuramic acid
      linkage to recycle peptidoglycan in the cytoplasm and cleaves the GlcNAc-beta-O
      linkage of foreign O-GlcNAc-modified proteins in vivo, sabotaging the recombinant
      co-expression system.

PMID- 24140294
TI  - Relationship between medial plica and medial femoral condyle--a three-dimensional
      dynamic finite element model.
AB  - BACKGROUND: Many researches reported that the pathologic medial plica impinges on
      the facing medial femoral condyle during knee motion and leads to erosive changes
      of the articular cartilage. The purpose of this study was to construct a
      simplified three-dimensional dynamic finite element human knee model to evaluate
      the dynamics behaviour between different types of medial plicae with the facing
      medial femoral condyles during knee motion. METHODS: A three-dimensional dynamic
      finite element model composed of femur, tibia, covering cartilage and medial
      plica was developed. The kinematics of this simulation model was verified by
      previous findings during arthroscopic examination. The validated model was used
      to investigate and compare the magnitudes of the cyclic pressures acting on the
      cartilage of the medial femoral condyles by three different types of medial
      plicae with various Young's moduli. FINDINGS: All types of plicae remained in
      contact with the medial femoral condyles and shifted medially when the knees
      moved from extension to flexion. The contact pressures were positively correlated
      with the Young's moduli of the medial plicae. During the whole range of motion,
      the maximum contact pressures of all simulation scenarios occurred when the knees
      moved beyond 50 degrees  of flexion. When the Young's moduli of medial plicae
      were set greater than 60 MPa, all types of medial plicae would elicit contact
      pressures greater than 10 MPa on the medial femoral condyles. INTERPRETATION: The
      close relationship and possible high contact pressure between fibrotic medial
      plica and medial femoral condyle during knee motion might be a cause of cartilage
      damage on the medial femoral condyle and warrants further investigation.

PMID- 24140295
TI  - Could culicine mosquitoes transmit human malaria?
AB  - Human malaria is known to be transmitted strictly by anopheline mosquitoes.
      Culicine mosquitoes such as Aedes spp. and Culex spp. are important vectors of
      other human pathogens including viruses and filarial worms, but have never been
      observed to transmit mammalian malarias. Culicines do transmit avian malarias
      and, interestingly, allow partial development of mammalian-infectious Plasmodium
      parasites, implying that physiological barriers in the mosquitoes prevent
      parasite transmission. Although the mechanism(s) are not known, the mosquito
      immune system is probably involved in eliminating Plasmodium. However, Plasmodium
      has shown substantial capacity to adapt to new vectors, and current ecological
      changes caused by humans could promote adaptation of human-infectious Plasmodium
      parasites to culicines. Such an event could have widespread epidemiological
      implications and therefore merits attention. 

PMID- 24140296
TI  - Dexmedetomidine preserves attention/calculation when used for cooperative and
      short-term intensive care unit sedation.
AB  - PURPOSE: Differential effects on cognition were recently demonstrated between
      dexmedetomidine (DEX) and propofol (PRO) when used for cooperative sedation.
      Propofol was found to reduce cognition, whereas DEX improved cognition. To
      further discriminate these effects, we evaluated the effect of PRO vs DEX in
      selected areas of cognition. METHODS: This is a post hoc analysis of the Acute
      Neurologic Intensive Care Unit Sedation Trial and an investigator-initiated,
      prospective, randomized, double-blinded, crossover study, comparing the effect of
      PRO and DEX on cognition measure by the Johns Hopkins Adapted Cognitive Exam
      (ACE). A linear model analysis accounting for within-patient correlation of
      measures was used to estimate differences in ACE subscales between drugs.
      RESULTS: Propofol diminished adjusted scores on all ACE subscales (P < .05),
      whereas DEX improved adjusted scores selectively for attention/calculation (3.55;
      95% confidence interval, 1.49-5.61; P < .01). The positive and significant
      difference in ACE scores between agents was present across subscales.
      CONCLUSIONS: Our findings indicate that DEX improved ACE attention/calculation
      subscale in awake patients receiving cooperative sedation. This is in contrast to
      the deterioration in all mean ACE subscale scores observed using PRO, suggesting
      DEX preserved cognitive function with specific preservation of focus and
      attention and allows for greater cognition compared with PRO across all cognitive
      domains.

PMID- 24140297
TI  - Does high-dose vasopressor therapy in medical intensive care patients indicate
      what we already suspect?
AB  - PURPOSE: This study was conducted to determine the association between
      vasopressor requirement and outcome in medical intensive care patients in an
      environment where treatment is not withdrawn. MATERIALS AND METHODS: This was an
      observational study of patients in the medical intensive care unit (ICU) over a
      period of 18 months to determine the correlation between vasopressor requirement
      and mortality. Outcome was determined for all medical ICU patients, for patients
      receiving "low dose" (<40 MUg/min) vasopressors (noradrenaline and/or adrenaline)
      or "high dose" (>= 40 MUg/min) vasopressors. Receiver operator characteristic
      curves were constructed for ICU and hospital mortality and high-dose vasopressor
      use. High-dose vasopressor use as an independent predictor for ICU and hospital
      mortality was also determined by multiple logistic regression analysis. RESULTS:
      Patients receiving high-dose noradrenaline at any time during their ICU admission
      had an 84.3% mortality in ICU and 90% in hospital. The receiver operator
      characteristic curves for high-dose vasopressors had an area under the curve of
      0.799 for ICU mortality and 0.779 for hospital mortality. High-dose vasopressor
      was an independent predictor of ICU mortality, with an odds ratio of 5.1
      (confidence interval, 2.02-12.9; P = .001), and of hospital mortality, with an
      odds ratio of 3.82 (confidence interval 1.28-11.37; P = .016). CONCLUSIONS: The
      requirement for high-dose vasopressor therapy at any time during ICU admission
      was associated with a very high mortality rate in the ICU and the hospital.

PMID- 24140298
TI  - Severe hyperkalemia can be detected immediately by quantitative
      electrocardiography and clinical history in patients with symptomatic or extreme
      bradycardia: a retrospective cross-sectional study.
AB  - PURPOSE: Detecting severe hyperkalemia is challenging. We explored its prevalence
      in symptomatic or extreme bradycardia and devised a diagnostic rule. MATERIALS
      AND METHODS: This retrospective cross-sectional study included patients with
      symptomatic (heart rate [HR] <= 50/min with dyspnea, chest pain, altered
      mentality, dizziness/syncope/presyncope, general weakness, oliguria, or shock) or
      extreme (HR <= 40/min) bradycardia at an emergency department for 46 months. Risk
      factors for severe hyperkalemia were chosen by multiple logistic regression
      analysis from history (sex, age, comorbidities, and medications), vital signs,
      and electrocardiography (ECG; maximum precordial T-wave amplitude, PR, and QRS
      intervals). The derived diagnostic index was validated using bootstrapping
      method. RESULTS: Among the 169 participants enrolled, 87 (51.5%) were female. The
      mean (SD) age was 71.2 (12.5) years. Thirty-six (21.3%) had severe hyperkalemia.
      The diagnostic summed "maximum precordial T >= 8.5 mV (2)," "atrial
      fibrillation/junctional bradycardia (1)," "HR <= 42/min (1)," "diltiazem
      medication (2)," and "diabetes mellitus (1)." The C-statistics were 0.86 (0.80
      0.93) and were validated. For scores of 4 or higher, sensitivity was 0.50,
      specificity was 0.92, and positive likelihood ratio was 6.02. The "ECG-only
      index," which sums the 3 ECG findings, had a sensitivity of 0.50, specificity of
      0.90, and likelihood ratio (+) of 5.10 for scores of 3 or higher. CONCLUSIONS:
      Severe hyperkalemia is prevalent in symptomatic or extreme bradycardia and
      detectable by quantitative electrocardiographic parameters and history.

PMID- 24140299
TI  - Two novel C-type lectins with a low-density lipoprotein receptor class A domain
      have antiviral function in the shrimp Marsupenaeus japonicus.
AB  - C-type lectins (CTLs) are pattern-recognition receptors (PRRs) that play
      important roles in immune response. In this study, two new CTLs containing a low
      density lipoprotein receptor class A domain (LDLR) and a carbohydrate recognition
      domain (CRD) were identified in Marsupenaeus japonicus and designated as LdlrLec1
      and LdlrLec2. The two CTLs expressed in all the tested tissues of shrimp,
      however, LdlrLec1 was mainly expressed in hemocytes, heart, gill and intestines,
      whereas LdlrLec2 was expressed in hepatopancreas and heart. The expression
      patterns of both LdlrLec1 and LdlrLec2 mRNA were obviously upregulated upon white
      spot syndrome virus (WSSV) challenge. Injection of recombinant LdlrLec1 or
      LdlrLec2 into shrimp inhibited WSSV replication, whereas knocking down the
      expression of LdlrLec1 and LdlrLec2 by RNA interference increased WSSV
      replication in vivo. The infection rates of WSSV incubated with LdlrLecs were
      reduced significantly compared with the control group. The LdlrLec proteins could
      interact with VP28, a major envelope protein of WSSV, which is necessary for the
      attachment and penetration of WSSV into shrimp cells. These results indicate that
      LdlrLec1 and LdlrLec2 may function in antiviral response by binding to WSSV and
      inhibiting their pervasion and replication in shrimp.

PMID- 24140300
TI  - Genotyping of potentially pathogenic Acanthamoeba strains isolated from nasal
      swabs of healthy individuals in Peru.
AB  - Free Living Amoebae (FLA) of Acanthamoeba genus are widely distributed in the
      environment and can be found in the air, soil and water; and have also been
      isolated from air-conditioning units. In humans, they are causative agents of a
      sight-threating infection of the cornea, Acanthamoeba keratitis (AK) and a fatal
      infection of the central nervous system known as Granulomatous Amoebic
      Encephalitis (GAE). In this study, a survey was conducted in order to determine
      the presence and pathogenic potential of free-living amoebae of Acanthamoeba
      genus in nasal swabs from individuals in two regions of Peru. Identification of
      isolates was based on cyst morphology and PCR-sequencing of the Diagnostic
      Fragment 3 to identify strains at the genotype level. The pathogenic potential of
      the isolates was also assayed using temperature and osmotolerance assays and
      extracellular proteases zymograms. The obtained results revealed that all
      isolated strains exhibited pathogenic potential. After sequencing the highly
      variable DF3 (Diagnostic Fragment 3) region in the 18S rRNA gene as previously
      described, genotype T4 was found to be the most common one in the samples
      included in this study but also genotype T15 was identified. To the best of our
      knowledge, this is the first study on the characterization of Acanthamoeba
      strains at the genotype level and the first report of genotype T4 and T15 in
      Peru. 

PMID- 24140301
TI  - Liver-brain interactions in inflammatory liver diseases: implications for fatigue
      and mood disorders.
AB  - Chronic inflammatory liver diseases are often accompanied by behavior alterations
      including fatigue, mood disorders, cognitive dysfunction and sleep disturbances.
      These altered behaviors can adversely affect patient quality of life. The
      communication pathways between the inflamed liver and the brain that mediate
      changes in central neural activity leading to behavior alterations during liver
      inflammation are poorly understood. Neural and humoral communication pathways
      have been most commonly implicated as driving peripheral inflammation to brain
      signaling. Classically, the cytokines TNFalpha, IL-1beta and IL-6 have received
      the greatest scientific attention as potential mediators of this communication
      pathway. In mice with liver inflammation we have identified a novel immune
      mediated liver-to-brain communication pathway whereby CCR2(+) monocytes found
      within the peripheral circulation transmigrate into the brain parenchyma in
      response to MCP-1/CCL2 expressing activated microglia. Inhibition of cerebral
      monocyte infiltration in these mice significantly improved liver inflammation
      associated sickness behaviors. Importantly, in recent work we have found that at
      an earlier time point, when cerebral monocyte infiltration is not evident in mice
      with liver inflammation, increased monocyte:cerebral endothelial cell adhesive
      interactions are observed using intravital microscopy of the brain. These
      monocyte:cerebral endothelial cell adhesive interactions are P-selectin mediated,
      and inhibition of these interactions attenuated microglial activation and
      sickness behavior development. Delineating the pathways that the periphery uses
      to communicate with the brain during inflammatory liver diseases, and the central
      neurotransmitter systems that are altered through these communication pathways
      (e.g., serotonin, corticotrophin releasing hormone) to give rise to liver
      inflammation-associated sickness behaviors, will allow for the identification of
      novel therapeutic targets to decrease the burden of debilitating symptoms in
      these patients. 

PMID- 24140302
TI  - Association between serum brain-derived neurotrophic factor and plasma
      interleukin-6 in major depressive disorder with melancholic features.
AB  - Inflammatory processes as well as attenuation of brain-derived neurotrophic
      factor (BDNF) availability are involved in the pathophysiology of major
      depressive disorder (MDD). Although it is generally presumed that these two
      systems interact negatively in the brain, preclinical and human in vitro studies
      have shown synergistic rather than antagonistic interactions in the periphery. We
      therefore examined the association between serum levels of BDNF and plasma levels
      of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in patients
      with MDD (n=1070) and non-depressed controls (n=379) from the Netherlands Study
      of Depression and Anxiety. We used multiple regression analyses with serum BDNF
      as the dependent variable and we specifically tested the presence of BDNF
      cytokine associations in DSM-IV-assigned melancholic MDD patients, identified by
      the Inventory of Depressive Symptomatology. After adjustment for
      sociodemographics, sampling variability, lifestyle indicators, somatic diseases
      and medication use, BDNF levels were predicted by the interaction between MDD
      diagnosis and IL-6 (p-interaction=.006). Stratified analyses showed that BDNF
      levels are indeed positively associated with IL-6 levels in MDD patients
      (beta=.07, p=.02), but not in non-depressed controls (beta=-.07, p=.23). When
      further stratified for melancholic and non-melancholic MDD (p-interaction=.005),
      IL-6 emerged as a robust positive predictor of BDNF only in the melancholic
      sample (beta=.21, p=.01), wherein serum BDNF levels were accordingly enhanced.
      Post-hoc exploratory analyses verified an accentuated positive association of
      BDNF levels with leucocyte counts in melancholia. No significant associations
      emerged between BDNF and TNF-alpha. Overall, our cross-sectional approach may
      have disclosed an allostatic, BDNF-inducing component of peripheral immunity
      and/or an immunotrophic function of peripheral BDNF. Both scenarios may warrant
      further exploration, as they could inform new research concepts towards immune
      based antidepressive treatment strategies. 

PMID- 24140303
TI  - Factors associated with weight changes in successful quitters participating in a
      smoking cessation program.
AB  - OBJECTIVE: To identify possible predictors of post-cessation weight gain in
      smoking abstainers. PATIENTS AND METHODS: A sample of 607 successful abstainers
      seen at the Centre for Tobacco-Dependent in Prague, Czech Republic, between 2005
      and 2010, was included in this analysis. This sample was followed up for 1year
      and included 47.9% women (N=291) with the mean age of 48years (18-85). FINDINGS:
      Post-cessation weight gain occurred in 88.6% of the 607 abstainers. The mean
      weight gain after one year post-quit was 5.1kg (95% confidence interval 4.7
      5.5kg). Baseline characteristics associated with increased weight gain included a
      higher baseline smoking rate (p<0.001), more severe cigarette dependence
      (p=0.003), less physical activity (p=0.008), and a report of increased appetite
      on the baseline assessment of withdrawal symptoms (p<0.001). CONCLUSIONS: Smokers
      who are more dependent and have minimal physical activity are at increased risk
      for post-cessation weight gain. For these smokers, incorporating interventions
      targeting the weight issue into tobacco dependence treatment is recommended.
      Further research should be done to identify reasons for this important quitting
      complication.

PMID- 24140305
TI  - Adolescent internet use and its relationship to cigarette smoking and alcohol
      use: a prospective cohort study.
AB  - The present study aims to investigate the longitudinal impact of situational
      Internet use on future cigarette smoking and alcohol use among male and female
      adolescents. A Northern Taiwanese cohort sample of adolescents with no prior use
      of cigarettes (n=1445) or alcohol (n=1468) was surveyed at age 16 and again 4
      years later. Information regarding where, why, and length of time spent using the
      Internet was gathered from the 16-year-old participants. Outcome information
      regarding cigarette/alcohol use was gathered via a follow-up questionnaire at age
      20. Multivariate regressions were used to incorporate peer, individual and family
      characteristics as measured at age 16 and create models of future cigarette and
      alcohol use at age 20. The analyses demonstrated that adolescent Internet use,
      particularly where such use took place, has a significant impact on future
      cigarette smoking and alcohol use, adjusted for conventional factors, and its
      relationship differs significantly by gender. Female adolescents with Internet
      cafe use appear to be especially likely to develop these two risky behaviors. The
      why of Internet use is also a predictor of future cigarette smoking. Finally,
      time spent using the Internet is significantly related to alcohol use; greater
      use of the Internet is associated with higher levels of drinking. The results
      revealed that different risky behaviors are differentially influenced by separate
      components of adolescent Internet use. These findings suggest that programs aimed
      at promoting adolescent health could potentially benefit Taiwanese adolescents by
      including components related to situational Internet use and taking gender into
      consideration.

PMID- 24140304
TI  - Relationships between problematic internet use and problem-gambling severity:
      findings from a high-school survey.
AB  - With the popularity of Internet use among adolescents, there is concern that some
      youth may display problematic or addictive patterns of Internet use. Although
      excessive patterns of Internet use was considered for inclusion in the DSM-5 with
      pathological gambling and substance-use disorders in a category of addictive
      disorders, it was determined that more research was needed on Internet-use
      behaviors before such actions be further considered and possibly undertaken. The
      present study is the first to investigate whether at-risk/problematic Internet
      use (ARPIU) may moderate the strength of association between problem-gambling
      severity and gambling-related characteristics and health and well-being measures
      in adolescents. Survey data from 1884 Connecticut high-school student stratified
      by Internet use (ARPIU vs. non-ARPIU) were examined in bivariate analyses and
      logistic regression models. Gambling-related characteristics and health and well
      being measures were mostly positively associated with problem-gambling severity
      in both Internet use groups. Interaction odds ratio revealed that the strength of
      the associations between problem-gambling severity and marijuana, alcohol and
      caffeine use were stronger amongst the non-ARPIU compared to the ARPIU group,
      suggesting that the relationships between these substance use behaviors and
      problem gambling may be partially accounted for by ARPIU. Future studies should
      examine the extent to which preventative interventions targeting both problematic
      Internet use and problem gambling may synergistically benefit measures of health
      and reduce risk-taking behaviors in adolescence. 

PMID- 24140306
TI  - Alcohol and drug treatment outcome studies: new methodological review (2005-2010)
      and comparison with past reviews.
AB  - OBJECTIVE: Several methodological reviews of alcohol treatment outcome studies
      and one review of drug studies have been published over the past 40 years.
      Although past reviews demonstrated methodological improvements in alcohol
      studies, they also found continued deficiencies. The current review allows for an
      updated evaluation of the methodological rigor of alcohol and drug studies and,
      by utilizing inclusion criteria similar to previous reviews, it allows for a
      comparative review over time. In addition, this is the first review that compares
      the methodology of alcohol and drug treatment outcome studies published during
      the same time period. METHOD: The methodology for 25 alcohol and 11 drug
      treatment outcome studies published from 2005 through 2010 that met the review's
      inclusion criteria was evaluated. The majority of variables evaluated were used
      in prior reviews. RESULTS: The current review found that more alcohol and drug
      treatment outcome studies are now using continuous substance use measures and
      assessing problem severity. Although there have been methodological improvements
      over time, the current reviews differed little from their most recent past
      counterpart. Despite this finding, some areas, particularly the continued low
      reporting of demographic data, needs strengthening. CONCLUSIONS: Improvement in
      the methodological rigor of alcohol and drug treatment outcome studies has
      occurred over time. The current review found few differences between alcohol and
      drug study methodologies as well as few differences between the current review
      and the most recent past alcohol and drug reviews.

PMID- 24140307
TI  - [Evaluation of a functional plan for caregivers in hospital].
AB  - BACKGROUND: The care of dependent persons has increased, as such that healthcare
      reforms are taking caregivers into account. A functional plan in hospitalization
      was developed for caregivers, and his study aims to investigate its
      implementation, identifying the strengths and weaknesses that promote changes
      between the formal and informal system. METHODS: A qualitative study was
      designed, using nursing professionals and caregivers identified in the hospital
      as subjects. A focus group technique was used with 8 people selected for each
      segment. Two scripts were developed with questions on the evaluation criteria
      included in the plan: identification/recruitment, reception, rest, diet, health
      care, information/health education, management and implementation of the plan and
      other proposals. The data were collected during May 2011. RESULTS: Difficulties
      were encountered in identifying caregivers, as an initial evaluation was not
      made. As regards the reception, in some cases the information brochure was not
      given. Rest was not possible as the caregivers did not want to move away from the
      patient. Diet was the main cause of the conflict, highlighting the lack of health
      education to continue in home care. Circuits of preferential care in emergency
      were positively valuated. Nurses consider the plan as an extra task. CONCLUSIONS:
      The strengths and weaknesses identified should enable improvements to be made in
      the implementation of the plan, in order to achieve changes in specific aspects
      such as information/education, health, rest and diet of the caregivers. We
      emphasize the need to enhance the model change.

PMID- 24140308
TI  - Symposium: Futures in Reproduction. Opening remarks.

PMID- 24140309
TI  - A tribute to Bob.

PMID- 24140310
TI  - Non-invasive prenatal testing using massively parallel sequencing of maternal
      plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.
AB  - The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a
      rapid development of non-invasive prenatal testing. The recent advent of
      massively parallel sequencing has allowed the analysis of circulating cell-free
      fetal DNA to be performed with unprecedented sensitivity and precision. Fetal
      trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such
      analyses have been available clinically since 2011. Fetal genome-wide molecular
      karyotyping and whole-genome sequencing have now been demonstrated in a number of
      proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma
      has been shown to allow the non-invasive prenatal testing of beta-thalassaemia
      and can potentially be generalized to other monogenic diseases. It is thus
      expected that plasma DNA-based non-invasive prenatal testing will play an
      increasingly important role in future obstetric care. It is thus timely and
      important that the ethical, social and legal issues of non-invasive prenatal
      testing be discussed actively by all parties involved in prenatal care.

PMID- 24140312
TI  - Complete Resolution of Retroperitoneal Lymphangioma with a Single Trial of OK-432
      in an Infant.
AB  - Retroperitoneal lymphangioma is extremely rare. Although these neoplasms are
      benign, they can grow progressively with subsequent compression and infiltration
      of the adjacent structures. Surgical excision is demanding when the lesion
      surrounds vital structures and it is generally fraught with a high recurrence and
      morbidity rate. We report the case of a huge retroperitoneal lymphangioma in a
      newborn treated successfully with intracystic injection of OK-432.

PMID- 24140313
TI  - Technical note: Use of laser capture microdissection for the localization of
      tissue-specific global gene expression in rumen papillae.
AB  - Gene expression profiling of bovine rumen tissue has provided insight into
      dietary regulation of rumen epithelial function. However, most studies have
      relied on a heterogeneous sample with multiple tissue and cell types. The
      objective of this study was to use laser capture microdissection to characterize
      RNA expression profiling of epithelial and connective tissues of rumen papillae.
      Papillae were biopsied from 3 lactating dairy cows, frozen in cryomolds, cut into
      sections, stained, and dehydrated, and epithelial and connective cells were
      collected using laser capture microdissection. Total RNA was isolated from
      epithelial and connective tissue and global gene expression was assessed using
      the Affymetrix GeneChip Bovine Gene 1.0 ST array (Affymetrix, Santa Clara, CA).
      Data preprocessing was conducted using the robust multi-array average method, and
      detection of differentially expressed genes (DEG) was determined using ANOVA. The
      model included the fixed effect of tissue, and a Benjamini-Hochberg false
      discovery rate of 0.1 was applied to DEG. We found 382 DEG between epithelial and
      connective tissues. Analysis of these DEG using Ingenuity Pathway Analysis
      (Redwood City, CA) found that epithelial and connective tissues in rumen papillae
      expressed distinct RNA profiles (signatures). The epithelial signature was
      enriched with RNA encoding tight junction and metabolic genes, whereas connective
      signatures were enriched with RNA encoding proteins involved in cell structure
      and extracellular matrix composition. The molecular functions enriched within the
      top networks between the 2 tissues from the Ingenuity Pathway Analysis included
      connective tissue disorders, dermatological diseases and conditions,
      gastrointestinal disease, tissue morphology, and tissue development. In summary,
      it is possible to use laser capture microdissection for the localization of
      tissue-specific global gene expression in rumen papillae. This approach may be
      useful to improve the accuracy and interpretation of molecular measurements in
      future studies. 

PMID- 24140311
TI  - Fertility preservation in patients with haematological disorders: a retrospective
      cohort study.
AB  - This study investigated the factors associated with utilization of fertility
      preservation and the differences in treatments and outcomes by prior chemotherapy
      exposure in patients with haematological diseases. This study included all 67
      women with haematological diseases seen for fertility preservation consultation
      at two university hospitals between 2006 and 2011. Of the total, 49% had
      lymphoma, 33% had leukaemia, 7% had myelodysplastic syndrome and 4% had aplastic
      anaemia; 46% had prior chemotherapy; and 33% were planning for bone marrow
      transplantation, 33% pursued ovarian stimulation and 7% used ovarian tissue
      banking; and 48% of patients did not pursue fertility preservation treatment. All
      five cycle cancellations were in the post-chemotherapy group: three patients with
      leukaemia and two with lymphoma. Patients with prior chemotherapy had lower
      baseline antral follicle count (10 versus 22) and received more gonadotrophins to
      achieve similar peak oestradiol concentrations, with no difference in oocyte
      yield (10.5 versus 10) after adjustment for age. Embryo yield was similar between
      those who had prior chemotherapy and those who had not. Half of the patients with
      haematological diseases who present for fertility preservation have been exposed
      to chemotherapy. While ovarian reserve is likely impaired in this group, oocyte
      yield may be acceptable.

PMID- 24140314
TI  - Cold enzymatic bleaching of fluid whey.
AB  - Chemical bleaching of fluid whey and retentate with hydrogen peroxide (HP) alone
      requires high concentrations (100-500 mg of HP/kg) and recent studies have
      demonstrated that off-flavors are generated during chemical bleaching that carry
      through to spray-dried whey proteins. Bleaching of fluid whey and retentate with
      enzymes such as naturally present lactoperoxidase or an exogenous commercial
      peroxidase (EP) at cold temperatures (4 degrees C) may be a viable alternative to
      traditional chemical bleaching of whey. The objective of this study was to
      determine the optimum level of HP for enzymatic bleaching (both lactoperoxidase
      and EP) at 4 degrees C and to compare bleaching efficacy and sensory
      characteristics to HP chemical bleaching at 4 degrees C. Selected treatments were
      subsequently applied for whey protein concentrate with 80% protein (WPC80)
      manufacture. Fluid Cheddar whey and retentate (80% protein) were manufactured in
      triplicate from pasteurized whole milk. The optimum concentration of HP (0 to 250
      mg/kg) to activate enzymatic bleaching at 4 degrees C was determined by
      quantifying the loss of norbixin. In subsequent experiments, bleaching efficacy,
      descriptive sensory analysis, and volatile compounds were monitored at selected
      time points. A control with no bleaching was also evaluated. Enzymatic bleaching
      of fluid whey and retentate at 4 degrees C resulted in faster bleaching and
      higher bleaching efficacy (color loss) than bleaching with HP alone at 250 mg/kg.
      Due to concentrated levels of naturally present lactoperoxidase, retentate
      bleached to completion (>80% norbixin destruction in 30 min) faster than fluid
      whey at 4 degrees C (>80% norbixin destruction in 12h). In fluid whey, the
      addition of EP decreased bleaching time. Spray-dried WPC80 from bleached wheys,
      regardless of bleaching treatment, were characterized by a lack of sweet aromatic
      and buttery flavors, and the presence of cardboard flavor concurrent with higher
      relative abundance of 1-octen-3-ol and 1-octen-3-one. Among enzymatically
      bleached WPC80, lactoperoxidase-bleached WPC80 contained higher relative
      abundance of 2,3-octadienone, 2-pentyl furan, and hexanal than those bleached
      with added EP. Bleach times, bleaching efficacy, and flavor results suggest that
      enzymatic bleaching may be a viable and desirable alternative to HP bleaching of
      fluid whey or retentate.

PMID- 24140315
TI  - Comparison of 2 electronic cowside tests to detect subclinical ketosis in dairy
      cows and the influence of the temperature and type of blood sample on the test
      results.
AB  - The objective of this study was to determine the suitability of 2 electronic hand
      held devices [FreeStyle Precision (FSP), Abbott GmbH & Co. KG, Wiesbaden, Germany
      and GlucoMen LX Plus (GLX), A. Menarini GmbH, Vienna, Austria] for measuring beta
      hydroxybutyrate (BHBA) in dairy cows. Three experiments were conducted to
      evaluate (1) the diagnostic performance of the devices, (2) the effect of the
      type of blood sample, and (3) the influence of the ambient temperature on the
      determined results. A total of 415 blood samples from lactating Holstein and
      Simmental cows were collected and analyzed with both devices (whole blood) and in
      a laboratory (serum). Correlation coefficients between whole-blood and serum BHBA
      concentrations were highly significant, with 94% for the FSP and 80% for the GLX
      device. Based on thresholds for subclinical ketosis of 1.2 and 1.4 mmol of
      BHBA/L, results obtained with the hand-held devices were evaluated by receiver
      operating characteristics analyses. This resulted in adjusted thresholds of 1.2
      and 1.4 mmol/L for the FSP and 1.1 and 1.3 mmol/L for the GLX device. Applying
      these thresholds, sensitivities were 98 and 100% for the FSP and 80 and 86% for
      the GLX device, respectively. Corresponding specificities were 90 and 97% for the
      FSP and 87 and 96% for the GLX device, respectively. Additionally, concentrations
      of BHBA were tested with both devices in whole blood, EDTA-added whole blood, and
      in their resulting serum and plasma, collected from 65 animals. Determined BHBA
      concentrations were similar within each device for whole and EDTA-added blood,
      and in serum and plasma, but differed between whole blood and serum and between
      EDTA-added blood and plasma. Blood samples with low (0.4 mmol/L), medium (1.1
      mmol/L), and high (1.6 mmol/L) BHBA concentrations were stored between +5 to +32
      degrees C and analyzed repeatedly at temperature levels differing by 4 degrees C.
      Additionally, devices and test strips were stored at equal conditions and used
      for measurement procedures. Storage temperature of the devices and test strips
      did not influence the differences between the results of the laboratory and the
      devices, whereas the temperature of the blood samples caused significant
      differences. Although the level of agreement between the laboratory and the GLX
      device was lower than for the laboratory and the FSP device, both devices are
      useful tools for monitoring subclinical ketosis in dairy cows. Due to their
      effects on the determined results, the type and temperature of the tested sample
      should be considered.

PMID- 24140316
TI  - Monitoring the ripening process of Cheddar cheese based on hydrophilic component
      profiling using gas chromatography-mass spectrometry.
AB  - We proposed an application methodology that combines metabolic profiling with
      multiple appropriate multivariate analyses and verified it on the industrial
      scale of the ripening process of Cheddar cheese to make practical use of
      hydrophilic low-molecular-weight compound profiling using gas chromatography-mass
      spectrometry to design optimal conditions and quality monitoring of the cheese
      ripening process. Principal components analysis provided an overview of the
      effect of sodium chloride content and kind of lactic acid bacteria starter on the
      metabolic profile in the ripening process of Cheddar cheese and orthogonal
      partial least squares-discriminant analysis unveiled the difference in
      characteristic metabolites. When the sodium chloride contents were different (1.6
      and 0.2%) but the same lactic acid bacteria starter was used, the 2 cheeses were
      classified by orthogonal partial least squares-discriminant analysis from their
      metabolic profiles, but were not given perfect discrimination. Not much
      difference existed in the metabolic profile between the 2 cheeses. Compounds
      including lactose, galactose, lactic acid, 4-aminobutyric acid, and phosphate
      were identified as contents that differed between the 2 cheeses. On the other
      hand, in the case of the same salt content of 1.6%, but different kinds of lactic
      acid bacteria starter, an excellent distinctive discrimination model was
      obtained, which showed that the difference of lactic acid bacteria starter caused
      an obvious difference in metabolic profiles. Compounds including lactic acid,
      lactose, urea, 4-aminobutyric acid, galactose, phosphate, proline, isoleucine,
      glycine, alanine, lysine, leucine, valine, and pyroglutamic acid were identified
      as contents that differed between the 2 cheeses. Then, a good sensory prediction
      model for "rich flavor," which was defined as "thick and rich, including umami
      taste and soy sauce-like flavor," was constructed based on the metabolic profile
      during ripening using partial least squares regression analysis. The amino acids
      proline, leucine, valine, isoleucine, pyroglutamic acid, alanine, glutamic acid,
      glycine, lysine, tyrosine, serine, phenylalanine, methionine, aspartic acid, and
      ornithine were extracted as ripening process markers. The present study is not
      limited to Cheddar cheese and can be applied to various maturation-type natural
      cheeses. This study provides the technical platform for designing optimal
      conditions and quality monitoring of the cheese ripening process. 

PMID- 24140317
TI  - Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by
      inhibition of autophagy at a late stage.
AB  - Gastric cancer is one of the most common malignant cancers, with poor prognosis
      and high mortality rates worldwide. Therefore, development of an effective
      therapeutic method without side effects is an urgent need. It has been reported
      that cationic antimicrobial peptides can selectively bind to negatively charged
      prokaryotic and cancer cell membranes and exert cytotoxicity without causing
      severe drug resistance. In the current study, we prepared a series of peptide
      fragments derived from bovine lactoferrin and evaluated their anticancer potency
      toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25
      AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent
      anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited
      AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory
      concentration (IC50) value of 64 MUM. Flow cytometry showed a notable increment
      of the sub-G1 populations of the cell cycle, indicating the induction of
      apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25
      treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP
      ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related
      LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and
      autophagy are involved in the early stage of LFcinB25-induced cell death of AGS
      cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to
      decrease, whereas cleaved beclin-1 increased in a time-dependent manner,
      suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit
      autophagy, thus enhancing apoptosis at the final stage. These findings provide
      support for future application of LFcinB25 as a potential therapeutic agent for
      gastric cancer.

PMID- 24140318
TI  - Effects of weekly regrouping of prepartum dairy cows on innate immune response
      and antibody concentration.
AB  - Objectives were to evaluate the effects of a stable prepartum grouping strategy
      on innate immune parameters, antibody concentration, and cortisol and haptoglobin
      concentrations of Jersey cows. Cows (253+/-3 d of gestation) were paired by
      gestation length and assigned randomly to the stable (all-in-all-out; AIAO) or
      traditional (TRD) treatment. In the AIAO treatment, groups of 44 cows were moved
      into a pen where they remained for 5 wk, whereas in the TRD treatment,
      approximately 10 cows were moved into a pen weekly to maintain stocking density
      (44 cows for 48 headlocks). Pens were identical in size and design and each pen
      received each treatment a total of 3 times (6 replicates; AIAO, n=259; TRD,
      n=308). A subgroup of cows (n=34/treatment) was selected on wk 1 of each
      replicate from which blood was sampled weekly from d -14 to 14 (d 0=calving) to
      determine polymorphonuclear leukocyte (PMNL) phagocytosis, oxidative burst, and
      expression of CD18 and L-selectin, hemogram, cortisol and glucose concentrations,
      and haptoglobin concentration. Another subgroup of cows (n=40/treatment) selected
      on wk 1 of each replicate was treated with chicken egg ovalbumin on d -21, -7,
      and 7 and had blood sampled weekly from d -21 to 21 for determination of
      immunoglobulin G anti-ovalbumin. All cows (n=149) had blood sampled weekly for
      nonesterified fatty acid (NEFA) and beta-hydroxybutyrate (BHBA) concentrations
      from d -21 to 21. Treatment did not affect percentage of PMNL positive for
      phagocytosis and oxidative burst (AIAO=64.3+/-2.9 vs. TRD=64.3+/-2.9%) and
      intensity of phagocytosis [AIAO=2,910.82+/-405.99 vs. TRD=2,981.52+/-406.87
      geometric mean fluorescence intensity (GMFI)] and oxidative burst
      (AIAO=7,667.99+/-678.29 vs. TRD=7,742.70+/-682.91 GMFI). Similarly, treatment did
      not affect the percentage of PMNL expressing CD18 (AIAO=96.3+/-0.7 vs. TRD=97.8+/
      0.7%) and L-selectin (AIAO=44.1+/-2.8 vs. TRD=45.1+/-2.8%) or the intensity of
      expression of CD18 (AIAO=3,496.2+/-396.5 vs. TRD=3,598.5+/-396.9 GMFI) and L
      selectin (AIAO=949.8+/-22.0 vs. TRD=940.4+/-22.3 GMFI). Concentration of
      immunoglobulin G anti-ovalbumin was not affected by treatment (AIAO=0.98+/-0.05
      vs. TRD=0.98+/-0.05 OD). The percentage of leukocytes classified as granulocyte
      (AIAO=38.9+/-1.5 vs. TRD 38.2+/-1.5%) and the granulocyte:lymphocyte ratio
      (AIAO=0.75+/-0.04 vs. TRD=0.75+/-0.04) were not affected by treatment.
      Concentrations of cortisol (AIAO=14.95+/-1.73 vs. TRD=18.07+/-1.73 ng/mL),
      glucose (AIAO=57.6+/-1.5 vs. TRD=60.0+/-1.5 ng/mL), and haptoglobin (AIAO=3.09+/
      0.48 vs. TRD=3.51+/-0.49 OD) were not affected by treatment. According to the
      current experiment, a stable prepartum grouping strategy does not improve innate
      immune parameters or antibody concentration compared with weekly prepartum
      regrouping.

PMID- 24140319
TI  - Reliability of genomic evaluations in Holstein-Friesians using haplotypes based
      on the BovineHD BeadChip.
AB  - The objectives of this study were to make subsets of high-density (HD) loci based
      on localized haplotype clusters, without loss of genomic information, to reduce
      computing time compared with the use of all HD loci and to investigate the effect
      on the reliability of the direct genomic value (DGV) when using this HD subset
      based on localized haplotype clusters in the genomic evaluation for Holstein
      Friesians. The DNA was isolated from semen samples of 548 bulls (key ancestors)
      of the EuroGenomics Consortium, a collaboration between 4 European dairy cattle
      breeding organizations and scientific partners. These bulls were genotyped with
      the BovineHD BeadChip [~777,000 (777K) single nucleotide polymorphisms (SNP);
      Illumina Inc., San Diego, CA] and used to impute all 30,483 Holstein-Friesians
      from the BovineSNP50 BeadChip [~50,000 (50K) SNP; Illumina Inc.] to HD, using the
      BEAGLE software package. The final data set consisted of 30,483 animals and
      603,145 SNP. For each locus, localized haplotype clusters (i.e., edges of the
      fitted graph model) identifications were obtained from BEAGLE. Three subsets
      [38,000 (38K), 116,000 (116K), and 322,000 (322K) loci] were made based on
      deleting obsolete loci (i.e., loci that do not give extra information compared
      with the neighboring loci). A fourth data set was based on 38K SNP, which is
      currently used for routine genomic evaluation at the Cattle Improvement
      Cooperative (CRV, Arnhem, the Netherlands). A validation study using the HD loci
      subsets based on localized haplotype clusters was performed for 9 traits
      (production, conformation, and functional traits). Error of imputation from 50K
      to HD averaged 0.78%. Three thresholds (0.17, 0.05, and 0.008%) were used for the
      identification of obsolete HD loci based on localized haplotype clusters to
      obtain a desired number of HD loci (38K, 116K, and 322K). On average, 46% (using
      threshold 0.008%) to 93% (using threshold 0.17%) of HD loci were eliminated. The
      computing time was about 9 d for 38K loci, 15.5d for 116K loci, 21d for 322K
      loci, and 7.5 d for 38K SNP. The increase in reliability of DGV compared with
      pedigree-based estimated breeding values for kilograms of protein was similar for
      322K and 116K loci (30.7%), but was 1.5 to 2% higher compared with 38K loci and
      38K SNP. Averaged over 9 traits, subset 116K loci resulted in a higher increase
      in reliability compared with 38K loci and 38K SNP. Eliminating obsolete loci
      enormously decreased the amount of data to be analyzed for genomic evaluations.
      The more HD loci used in a genomic evaluation, the higher the increase in
      reliability of DGV. It is possible to increase the reliability of DGV by 1 to 2%
      compared with the SNP currently used for routine genomic evaluation.

PMID- 24140320
TI  - Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on
      enterohemorrhagic Escherichia coli infection using mouse and intestinal cell
      models.
AB  - A potential probiotic strain, Lactobacillus kefiranofaciens M1, was previously
      isolated from kefir grains, which are used to manufacture the traditional
      fermented drink kefir. The aim of this study was to investigate the effects of
      Lb. kefiranofaciens M1 on enterohemorrhagic Escherichia coli (EHEC) infection,
      using mice and intestinal cell models. BALB/c mice were daily administrated with
      either phosphate buffered saline or Lb. kefiranofaciens M1 at 2*10(8) cfu/mouse
      per day intragastrically for 7 d. Intragastric challenges with EHEC (2*10(9)
      cfu/mouse) were conducted on d 0, 4, and 7 after treatment. Administration of Lb.
      kefiranofaciens M1 was able to prevent EHEC infection-induced symptoms,
      intestinal damage, renal damage, bacterial translocation, and Shiga toxin
      penetration. Furthermore, the mucosal EHEC-specific IgA responses were increased
      after Lb. kefiranofaciens M1 administration in the EHEC-infected mouse system.
      Additionally, in vitro, Lb. kefiranofaciens M1 was shown to have a protective
      effect on Caco-2 intestinal epithelial cells and Caco-2 intestinal epithelial
      cell monolayers; the bacteria limited EHEC-induced cell death and reduced the
      loss of epithelial integrity. These findings support the potential of Lb.
      kefiranofaciens M1 treatment as an approach to preventing EHEC infection and its
      effects. 

PMID- 24140321
TI  - Expanding the bovine milk proteome through extensive fractionation.
AB  - Bovine milk is an agricultural product of tremendous value worldwide. It contains
      proteins, fat, lactose, vitamins, and minerals. It provides nutrition and
      immunological protection (e.g., in the gastrointestinal tract) to the newborn and
      young calf. It also forms an important part of human nutrition. The repertoire of
      proteins in milk (i.e., its proteome) is vast and complex. The milk proteome can
      be described in detail by mass spectrometry-based proteomics. However, the high
      concentration of dominating proteins in milk reduces mass spectrometry detection
      sensitivity and limits detection of low abundant proteins. Further, the general
      health and udder health of the dairy cows delivering the milk may influence the
      composition of the milk proteome. To gain a more exhaustive and true picture of
      the milk proteome, we performed an extensive preanalysis fractionation of raw
      composite milk collected from documented healthy cows in early lactation. Four
      simple and industrially applicable techniques exploring the physical and chemical
      properties of milk, including acidification, filtration, and centrifugation, were
      used for separation of the proteins. This resulted in 5 different fractions,
      whose content of proteins were compared with the proteins of nonfractionated milk
      using 2-dimensional liquid chromatography tandem mass spectrometry analysis. To
      validate the proteome analysis, spectral counts and ELISA were performed on 7
      proteins using the ELISA for estimation of the detection sensitivity limit of the
      2-dimensional liquid chromatography tandem mass spectrometry analysis. Each
      fractionation technique resulted in identification of a unique subset of
      proteins. However, high-speed centrifugation of milk to whey was by far the best
      method to achieve high and repeatable proteome coverage. The total number of milk
      proteins initially detected in nonfractionated milk and the fractions were 635 in
      2 replicates. Removal of dominant proteins and filtering for redundancy across
      the different fractions reduced the number to 376 unique proteins in 2
      replicates. In addition, 366 proteins were detected by this process in 1
      replicate. Hence, by applying different fractionation techniques to milk, we
      expanded the milk proteome. The milk proteome map may serve as a reference for
      scientists working in the dairy sector. 

PMID- 24140322
TI  - Dynamic changes in antibody levels as an early warning of Salmonella Dublin in
      bovine dairy herds.
AB  - Salmonella Dublin is a bacterium that causes disease and production losses in
      cattle herds. In Denmark, a surveillance and control program was initiated in
      2002 to monitor and reduce the prevalence of Salmonella Dublin. In dairy herds,
      the surveillance includes herd classification based on bulk tank milk
      measurements of antibodies directed against Salmonella Dublin at 3-mo intervals.
      In this study, an "alarm herd" concept, based on the dynamic progression of these
      repeated measurements, was formulated such that it contains predictive power for
      Salmonella Dublin herd classification change from "likely free of infection" to
      "likely infected" in the following quarter of the year, thus warning the farmer 3
      mo earlier than the present system. The alarm herd concept was defined through
      aberrations from a stable development over time of antibody levels. For suitable
      parameter choices, alarm herd status was a positive predictor for Salmonella
      Dublin status change in dairy herds, in that alarm herds had a higher risk of
      changing status in the following quarter compared with nonalarm herds. This was
      despite the fact that both alarm and nonalarm herds had antibody levels that did
      not indicate the herds being "likely infected" according to the existing
      classification system in the present quarter. The alarm herd concept can be used
      as a new early warning element in the existing surveillance program.
      Additionally, to improve accuracy of herd classification, the alarm herd concept
      could be incorporated into a model including other known risk factors for change
      in herd classification. Furthermore, the model could be extended to other
      diseases monitored in similar ways.

PMID- 24140323
TI  - Identification of virulence factors in 16S-23S rRNA intergenic spacer genotyped
      Staphylococcus aureus isolated from water buffaloes and small ruminants.
AB  - Staphylococcus aureus is an important human and animal pathogen, and is regarded
      as an important cause of intramammary infection (IMI) in ruminants.
      Staphylococcus aureus genetic variability and virulence factors have been well
      studied in veterinary medicine, especially in cows as support for control and
      management of IMI. The aim of the present study was to genotype 71 Staph. aureus
      isolates from the bulk tank and foremilk of water buffaloes (n=40) and from udder
      tissue (n=7) and foremilk (n=24) from small ruminants. The method used was
      previously applied to bovine Staph. aureus and is based on the amplification of
      the 16S-23S rRNA intergenic spacer region. The technique applied was able to
      identify different Staph. aureus genotypes isolated from dairy species other than
      the bovine species, and cluster the genotypes according to species and herds.
      Virulence gene distribution was consistent with genotype differentiation. The
      isolates were also characterized through determination of the presence of 19
      virulence-associated genes by specific PCR. Enterotoxins A, C, D, G, I, J, and L
      were associated with Staph. aureus isolates from buffaloes, whereas enterotoxins
      C and L were linked to small ruminants. Genes coding for methicillin resistance,
      Panton-Valentine leukocidin, exfoliative toxins A and B, and enterotoxins B, E,
      and H were undetected. These findings indicate that RNA template-specific PCR is
      a valid technique for typing Staph. aureus from buffaloes and small ruminants and
      is a useful tool for understanding udder infection epidemiology. 

PMID- 24140324
TI  - Nutritional and sensory characteristics of Minas fresh cheese made with goat
      milk, cow milk, or a mixture of both.
AB  - This study aimed to assess and compare the nutritional, technological, and
      sensory characteristics of Minas fresh cheese made with goat milk, cow milk, or a
      mixture of the two stored in cold conditions for 21d. The yield and centesimal
      composition of the cheeses were not affected by the type of milk used in their
      preparation. Reductions were observed in the moisture content, pH, proteolysis
      index, and instrumental hardness; moreover, increases were observed in the
      syneresis, acidity index, and depth of proteolysis index in all cheeses. The
      percentages of caprylic, capric, oleic, and linoleic fatty acids were higher in
      goat milk cheese and cheese made with a mixture of goat and cow milk compared
      with cow milk cheese, and a sensory evaluation revealed differences in color,
      flavor, and aroma between the cheeses. The preparation of Minas fresh cheese with
      a mixture of goat and cow milk can be a viable alternative for dairy products in
      the market that can be characterized as high-quality products that meet consumer
      demands. 

PMID- 24140325
TI  - Short communication: Changes in heart rate variability of dairy cows during
      conventional milking with nonvoluntary exit.
AB  - Heart rate variability (HRV), as a physiological measure of animal welfare, was
      investigated in 36 cows milked in a parallel milking parlor with nonvoluntary
      exit. Heart rate variability parameters measured during the morning resting
      (baseline period) were compared with those measured during different stages of
      the entire milking process. No differences were found in HRV parameters between
      the baseline period, preparation, and main milking. A considerable reduction in
      vagal activity was detected during the movement of the cows to the milking parlor
      (driving) and while cows were in the holding area. The parasympathetic measures
      of HRV decreased whereas the sympatho-vagal balance increased compared with
      baseline. The same pattern was observed regarding the stage between removing the
      teat cups and leaving the milking parlor (waiting). No differences in any
      sympathetic measures were observed between the baseline period and any of the
      milking stages. These findings indicate that the milking process itself
      (preparation and main milking) is not stressful for cows. Decreased
      parasympathetic activity during driving might be the result of the physical
      activity of the cows, whereas waiting in the holding area and in the milking
      stall after milking caused stress for animals. 

PMID- 24140326
TI  - Immune and production responses of dairy cows to postruminal supplementation with
      phytonutrients.
AB  - This study investigated the effect of phytonutrients (PN) supplied postruminally
      on nutrient utilization, gut microbial ecology, immune response, and productivity
      of lactating dairy cows. Eight ruminally cannulated Holstein cows were used in a
      replicated 4*4 Latin square. Experimental periods lasted 23 d, including 14-d
      washout and 9-d treatment periods. Treatments were control (no PN) and daily
      doses of 2g/cow of either curcuma oleoresin (curcumin), garlic extract (garlic),
      or capsicum oleoresin (capsicum). Phytonutrients were pulse-dosed into the
      abomasum of the cows, through the rumen cannula, 2 h after feeding during the
      last 9 d of each experimental period. Dry matter intake was not affected by PN,
      although it tended to be lower for the garlic treatment compared with the
      control. Milk yield was decreased (2.2 kg/d) by capsicum treatment compared with
      the control. Feed efficiency, milk composition, milk fat and protein yields, milk
      N efficiency, and 4.0% fat-corrected milk yield were not affected by treatment.
      Rumen fermentation variables, apparent total-tract digestibility of nutrients, N
      excretion with feces and urine, and diversity of fecal bacteria were also not
      affected by treatment. Phytonutrients had no effect on blood chemistry, but the
      relative proportion of lymphocytes was increased by the capsicum treatment
      compared with the control. All PN increased the proportion of total CD4(+) cells
      and total CD4(+) cells that co-expressed the activation status signal and CD25 in
      blood. The percentage of peripheral blood mononuclear cells (PBMC) that
      proliferated in response to concanavalin A and viability of PBMC were not
      affected by treatment. Cytokine production by PBMC was not different between
      control and PN. Expression of mRNA in liver for key enzymes in gluconeogenesis,
      fatty acid oxidation, and response to reactive oxygen species were not affected
      by treatment. No difference was observed due to treatment in the oxygen radical
      absorbance capacity of blood plasma but, compared with the control, garlic
      treatment increased 8-isoprostane levels. Overall, the PN used in this study had
      subtle or no effects on blood cells and blood chemistry, nutrient digestibility,
      and fecal bacterial diversity, but appeared to have an immune-stimulatory effect
      by activating and inducing the expansion of CD4 cells in dairy cows. Capsicum
      treatment decreased milk yield, but this and other effects observed in this study
      should be interpreted with caution because of the short duration of treatment.

PMID- 24140327
TI  - Effect of substitution of soybean meal by canola meal or distillers grains in
      dairy rations on amino acid and glucose availability.
AB  - Canola meal (CM) or by-products of ethanol production (dried distillers grain,
      DDG) may offer an economical alternative to soybean meal (SBM) in North American
      dairy rations. These protein supplements can effectively replace SBM and, in 2
      recent meta-analyses, CM had a positive effect on milk and milk protein yields
      compared with SBM. The objective of this study was to determine if the positive
      responses observed with inclusion of CM in dairy rations could be explained by an
      increased availability of His, Lys, Met, or glucose. Eight Holstein dairy cows
      were used in a replicated 4*4 Latin square with 14-d periods. Cows were fed
      isonitrogenous (17.2% crude protein) and isoenergetic (1.56 Mcal/kg of net energy
      of lactation) diets formulated to slightly exceed nutrient requirements. Diets
      contained 38% grass hay and 62% corn-based concentrate including SBM, CM, corn
      high-protein DDG (HPDDG), or wheat DDG plus solubles (WDDGS) as the single
      protein supplement. The effect of protein supplements on availability of His,
      Lys, Met, and glucose was estimated using variations in the whole-body (WB) flux
      of these nutrients, determined by isotopic dilution. As planned, dry matter
      intake and milk and milk protein yields were not affected by treatments and
      averaged 23.7, 31.4, and 1.14 kg/d, respectively. Lactose yield did not differ
      among diets although milk lactose content tended to be lower with CM and WDDGS
      diets than with SBM and HPDDG diets. Lysine availability was affected by
      treatments: the highest WB irreversible loss rate (ILR) was observed for the CM
      diet (371 g/d) and the lowest for HPDDG diet (290 g/d); values for SBM and WDDGS
      were intermediate (330 and 316 g/d, respectively). Availability of His and Met
      did not vary among diets and WB ILR averaged, respectively, 129 and 124 g/d; the
      CM diet, however, had numerically the highest His and Met ILR. Plasma
      concentrations of most of the essential AA were higher with the CM diet and lower
      with the HPDDG diet, the exception being Leu for which the concentration was
      highest for the HPDDG diet. Glucose WB rate of appearance was altered by diet,
      with the highest mean observed for SBM (3,036 g/d) and the lowest for CM (2,795
      g/d); the 2 diets with the lowest WB glucose rate of appearance (CM and WDDGS)
      also had the lowest dietary starch concentration. Overall, this study suggested
      that positive responses in milk and milk protein yields observed with inclusion
      of CM in dairy rations could be linked to a greater supply of metabolizable
      protein, including some essential AA, especially His, Lys, and Met, as glucose
      availability was certainly not increased in cows fed the CM diet.

PMID- 24140328
TI  - High-pressure processing decelerates lipolysis and formation of volatile
      compounds in ovine milk blue-veined cheese.
AB  - Enzyme-rich cheeses are prone to over-ripening during refrigerated storage. Blue
      veined cheeses fall within this category because of the profuse growth of
      Penicillium roqueforti in their interior, which results in the production of
      highly active proteinases, lipases, and other enzymes responsible for the
      formation of a great number of flavor compounds. To control the excessive
      formation of free fatty acids (FFA) and volatile compounds, blue-veined cheeses
      were submitted to high-pressure processing (HPP) at 400 or 600 MPa on d 21, 42,
      or 63 after manufacture. Cheeses were ripened for 30d at 10 degrees C and 93%
      relative humidity, followed by 60 d at 5 degrees C, and then held at 3 degrees C
      until d 360. High-pressure processing influenced the concentrations of acetic
      acid and short-chain, medium-chain, and long-chain FFA. The effect was dependent
      on treatment conditions (pressure level and cheese age at the time of treatment).
      The lowest concentrations of acetic acid and FFA were recorded for cheeses
      treated at 600 MPa on d 21; these cheeses showed the lowest esterase activity
      values. Acetic acid and all FFA groups increased during ripening and refrigerated
      storage. The 102 volatile compounds detected in cheese belonged to 10 chemical
      groups (5 aldehydes, 12 ketones, 17 alcohols, 12 acids, 35 esters, 9
      hydrocarbons, 5 aromatic compounds, 3 nitrogen compounds, 3 terpenes, and 1
      sulfur compound). High-pressure processing influenced the levels of 97 individual
      compounds, whereas 68 individual compounds varied during refrigerated storage.
      Total concentrations of all groups of volatile compounds were influenced by HPP,
      but only ketones, acids, esters, and sulfur compounds varied during refrigerated
      storage. The lowest total concentrations for most groups of volatile compounds
      were recorded for the cheese pressurized at 600 MPa on d 21. A principal
      component analysis combining total concentrations of groups of FFA and volatile
      compounds discriminated cheeses by age and by the pressure level applied to HPP
      cheeses.

PMID- 24140330
TI  - Sodium salicylate treatment in early lactation increases whole-lactation milk and
      milk fat yield in mature dairy cows.
AB  - Multiple lines of inquiry have suggested that a high degree of inflammation in
      early lactation cows is associated with low productivity and increased disease
      incidence. In addition, some small studies have suggested that milk production
      increases in response to antiinflammatory treatment in the first week of
      lactation. Our objective was to determine if administration of sodium salicylate
      (SS), a nonsteroidal antiinflammatory drug (NSAID), in the first week of
      lactation changes whole-lactation productivity and retention in the herd. At
      calving, 78 cows [n=39 primiparous (1P); n=24 second parity (2P); n=15 third
      parity or greater (3P)] were alternately assigned to either control (CON) or SS
      treatments for 7 d postpartum. Sodium salicylate treatment was administered via
      individual water bowls at a concentration of 1.95 g/L, delivering a mean of
      123.3+/-5.5 g of salicylate/d during the 7-d treatment. For the first 21 d of
      lactation, dry matter intake, water intake, milk yield, and health were monitored
      daily, and milk samples were collected twice weekly for milk component analysis.
      Monthly milk yield and component testing through the rest of the lactation
      provided data to assess long-term responses, and the effects of treatment on the
      risk of leaving the herd and on 305-d milk, fat, and protein yields were
      assessed. During the first 21 d of lactation, we observed no differences in
      morbidity, except for increased risk of metritis in 3P SS cows. Treatment
      interacted with parity to influence both 305-d milk and milk fat yields, and a
      tendency for an interaction was detected for 305-d milk protein yield. Milk yield
      was 2,469+/-646 kg greater over the lactation in 3P SS cows compared with 3P CON
      cows (21% increase) and tended to decrease by 8% in 1P cows treated with SS; no
      effects were detected in 2P cows. Furthermore, 3P SS cows produced 130+/-23 kg
      more milk fat over the lactation (30% increase), with no effects detected for 1P
      or 2P. Treatment with SS tended to increase 305-d milk protein yield in 3P cows
      by 14%, with no effects in 1P or 2P cows. A tendency for a treatment * parity
      interaction was also observed for the risk of leaving the herd. First-parity cows
      treated with SS tended to have greater risk of leaving the herd than controls (30
      vs. 6% risk); however, treatment did not alter herd retention in 2P or 3P groups,
      and SS had no effect on the risk of leaving the herd overall. Results indicate
      that SS has long-term effects on lactation of mature dairy cows, particularly on
      fat yield, but may have negative effects for primiparous cows.

PMID- 24140329
TI  - Effects of mineral content of bovine drinking water: does iron content affect
      milk quality?
AB  - The composition of water given to dairy cattle is often ignored, yet water is a
      very important nutrient and plays a major role in milk synthesis. The objective
      of this study was to study effects of elevated levels of iron in bovine drinking
      water on milk quality. Ferrous lactate treatments corresponding to 0, 2, 5, and
      12.5mg/kg drinking water concentrations were delivered through the abomasum at 10
      L/d to 4 lactating dairy cows over 4 periods (1 wk infusion/period) in a Latin
      square design. On d 6 of infusion, milk was collected, processed (homogenized,
      pasteurized), and analyzed. Mineral content (Fe, Cu, P, Ca) was measured by
      inductively coupled plasma mass spectrometry. Oxidative stability of whole
      processed milk was measured by the thiobarbituric acid reactive substances
      (TBARS) assay for malondialdehyde (MDA) and sensory analysis (triangle test)
      within 72 h of processing and after 7d of storage (4 degrees C). Significant
      sensory differences between processed milks from cows receiving iron and the
      control infusion were observed. No differences in TBARS (1.46+/-0.04 mg of
      MDA/kg) or mineral content (0.22+/-0.01 mg/kg Fe) were observed. A 2-way
      interaction (iron treatment by cow) for Ca, Cu, and Fe concentrations was seen.
      While iron added directly to milk causes changes in oxidation of milk, high
      levels of iron given to cattle have subtle effects that initially may not be
      obvious.

PMID- 24140331
TI  - Short communication: Comparison of ambient temperature, relative humidity, and
      temperature-humidity index between on-farm measurements and official
      meteorological data.
AB  - The objectives of the study were to compare the climate conditions of 7 dairy
      farms with the climate recorded at the closest official meteorological station.
      Specifically, we set out to compare the ambient temperature, relative humidity,
      and the resulting temperature-humidity index (THI) from 7 different barns with
      those data obtained from the closest official meteorological stations and to
      compare the climate conditions between 4 different locations within 1 barn.
      Measures of correlation and agreement demonstrated that climate conditions differ
      significantly between the barn and the corresponding official meteorological
      stations as well as between 4 different locations inside 1 barn. The ambient
      temperature was higher (6.4+/-3.6 degrees C) in the barn than at the official
      meteorological station. The relative humidity was higher at the official
      meteorological station (0.2+/-7.2%) than in the barn. The THI was higher (11.1+/
      6.5) in the barn than at the official meteorological station. Days with an
      average THI>=72 were 64 and 4 out of 756 experimental d in the barn and at the
      official meteorological station, respectively. Also, in a comparison of 7
      different barns, ambient temperature and THI were significantly higher than at
      the closest corresponding official meteorological station. These results indicate
      that climate conditions should be obtained from on-farm measurements to evaluate
      potential heat stress and to develop effective measures to abate heat stress of
      dairy cows. 

PMID- 24140332
TI  - Risk factors associated with bulk tank standard plate count, bulk tank coliform
      count, and the presence of Staphylococcus aureus on organic and conventional
      dairy farms in the United States.
AB  - The purpose of this study was to assess the association of bulk tank milk
      standard plate counts, bulk tank coliform counts (CC), and the presence of
      Staphylococcus aureus in bulk tank milk with various management and farm
      characteristics on organic and conventional dairy farms throughout New York,
      Wisconsin, and Oregon. Data from size-matched organic farms (n=192), conventional
      nongrazing farms (n=64), and conventional grazing farms (n=36) were collected at
      a single visit for each farm. Of the 292 farms visited, 290 bulk tank milk
      samples were collected. Statistical models were created using data from all herds
      in the study, as well as exclusively for the organic subset of herds. Because of
      incomplete data, 267 of 290 herds were analyzed for total herd modeling, and 173
      of 190 organic herds were analyzed for the organic herd modeling. Overall, more
      bulk tanks from organic farms had Staph. aureus cultured from them (62% of
      organic herds, 42% conventional nongrazing herds, and 43% of conventional grazing
      herds), whereas fewer organic herds had a high CC, defined as >=50 cfu/mL, than
      conventional farms in the study. A high standard plate count (*1,000 cfu/mL) was
      associated with decreased body condition score of adult cows and decreased milk
      production in both models. Several variables were significant only in the model
      created using all herds or only in organic herds. The presence of Staph. aureus
      in the bulk tank milk was associated with fewer people treating mastitis,
      increased age of housing, and a higher percentage of cows with 3 or fewer teats
      in both the organic and total herd models. The Staph. aureus total herd model
      also showed a relationship with fewer first-lactation animals, higher hock
      scores, and less use of automatic takeoffs at milking. High bulk tank CC was
      related to feeding a total mixed ration and using natural service in nonlactating
      heifers in both models. Overall, attentive management and use of outside
      resources were useful with regard to CC on organic farms. In all models except
      the organic CC model, we observed an association with the average reported
      somatic cell count from 3 mo before the herd visit, indicating that many of the
      regularly tested milk quality parameters are interconnected. In conclusion, we
      found that conventional and organic farms are similar in regard to overall herd
      management, but each grazing system faces unique challenges when managing milk
      quality.

PMID- 24140333
TI  - The effect of changing cow production and fitness traits on net income and
      greenhouse gas emissions from Australian dairy systems.
AB  - The aim of this study was to compare the effect of changing a range of biological
      traits on farm net income and greenhouse gas emissions (expressed in carbon
      dioxide equivalents, CO2-eq.) in the Australian dairy cow population. An average
      cow was modeled, using breed-average information for Holsteins and Jerseys from
      the Australian Dairy Herd Improvement Scheme. A Markov chain approach was used to
      describe the steady-state herd structure, as well as estimate the CO2-eq.
      emissions per cow and per kilogram of milk solids. The effects of a single unit
      change in herd milk volume, fat and protein yields, live weight, survival, dry
      matter intake, somatic cell count, and calving interval were assessed. With the
      traits studied, the only single-unit change that would bring about a desirable
      increase in both net income and reduced emissions intensity per cow and per
      kilogram of milk solids in Australian dairy herds would be an increase in
      survival and reductions in milk volume, live weight, DMI, SCC, and calving
      interval. The models developed can be used to assess lifetime dairy system
      abatement options by breeding, feeding, and management. Selective breeding and
      appropriate management can both improve health, fertility, and feed utilization
      of Australian dairy systems and reduce its environmental impact. 

PMID- 24140334
TI  - Shelf life of pasteurized microfiltered milk containing 2% fat.
AB  - The goal of this research was to produce homogenized milk containing 2% fat with
      a refrigerated shelf life of 60 to 90 d using minimum high temperature, short
      time (HTST) pasteurization in combination with other nonthermal processes. Raw
      skim milk was microfiltered (MF) using a Tetra Alcross MFS-7 pilot plant (Tetra
      Pak International SA, Pully, Switzerland) equipped with Membralox ceramic
      membranes (1.4 MUm and surface area of 2.31 m(2); Pall Corp., East Hills, NY).
      The unpasteurized MF skim permeate and each of 3 different cream sources were
      blended together to achieve three 2% fat milks. Each milk was homogenized (first
      stage: 17 MPa, second stage: 3 MPa) and HTST pasteurized (73.8 degrees C for
      15s). The pasteurized MF skim permeate and the 3 pasteurized homogenized 2% fat
      milks (made from different fat sources) were stored at 1.7 and 5.7 degrees C and
      the standard plate count for each milk was determined weekly over 90 d. When the
      standard plate count was >20,000 cfu/mL, it was considered the end of shelf life
      for the purpose of this study. Across 4 replicates, a 4.13 log reduction in
      bacteria was achieved by MF, and a further 0.53 log reduction was achieved by the
      combination of MF with HTST pasteurization (73.8 degrees C for 15s), resulting in
      a 4.66 log reduction in bacteria for the combined process. No containers of MF
      skim milk that was pasteurized after MF exceeded 20,000 cfu/mL bacteria count
      during 90 d of storage at 5.7 degrees C. The 3 different approaches used to
      reduce the initial bacteria and spore count of each cream source used to make the
      2% fat milks did not produce any shelf-life advantage over using cold separated
      raw cream when starting with excellent quality raw whole milk (i.e., low bacteria
      count). The combination of MF with HTST pasteurization (73.8 degrees C for 15s),
      combined with filling and packaging that was protected from microbial
      contamination, achieved a refrigerated shelf life of 60 to 90 d at both 1.7 and
      5.7 degrees C for 2% fat milks.

PMID- 24140335
TI  - Interdigital dermatitis, heel horn erosion, and digital dermatitis in 14
      Norwegian dairy herds.
AB  - The aim of this study was to assess infectious foot diseases, including
      identification and characterization of Dichelobacter nodosus and Treponema spp.,
      in herds having problems with interdigital dermatitis (ID) and heel horn erosion
      (E) and in control herds expected to have few problems. We also wanted to compare
      diseased and healthy cows in all herds. The study included 14 dairy herds with a
      total of 633 cows. Eight herds had a history of ID and E, and 6 were control
      herds. All cows were scored for lameness, and infectious foot diseases on the
      hind feet were recorded after trimming. Swabs and biopsies were taken from the
      skin of 10 cows in each herd for bacterial analyses. In total, samples were taken
      from 34 cows with ID, 11 with E, 40 with both ID and E, and 8 with digital
      dermatitis (DD), and from 47 cows with healthy feet. Swabs were analyzed for
      identification and characterization of D. nodosus by PCR, culture, virulence
      testing, and serotyping. Biopsies were analyzed by fluorescent in situ
      hybridization regarding histopathology, identification, and characterization of
      Treponema spp., and identification of D. nodosus. Interdigital dermatitis was the
      most frequent foot disease, with a prevalence of 50.4% in problem herds compared
      with 26.8% in control herds. Heel horn erosion was recorded in 34.8% of the cows
      in problem herds compared with 22.1% in control herds. Dichelobacter nodosus was
      detected in 97.1% of the cows with ID, in 36.4% with E, in all cows with both ID
      and E, in all cows with DD, and in 66.0% of cows with healthy feet. All
      serogroups of D. nodosus except F and M were detected, and all isolates were
      defined as benign by the gelatin gel test. Treponema spp. were detected in 50.0%
      of the cows with ID, in 9.1% with E, in 67.5% with ID and E, in all cows with DD,
      and in 6.4% of those with healthy feet. In total, 6 previously described
      phylotypes (PT) of Treponema were detected: PT1, PT3, PT6, PT13, and PT15 in cows
      with ID, PT1 in a cow with E, and PT1, PT2, PT3, PT6, and PT13 in cows with both
      ID and E. One new phylotype (PT19) was identified. The epidermal damage score was
      higher but the difference in inflammatory response of the dermis was minor in
      cows with ID versus those with healthy feet. Fisher's exact test revealed an
      association between ID and D. nodosus, and between ID and Treponema spp. Logistic
      regression revealed an association between both ID and E and dirty claws (odds
      ratios=1.9 and 2.0, respectively). Our study indicates that D. nodosus, Treponema
      spp., and hygiene are involved in the pathogenesis of ID. 

PMID- 24140336
TI  - Randomized clinical trial of tetracycline hydrochloride bandage and paste
      treatments for resolution of lesions and pain associated with digital dermatitis
      in dairy cattle.
AB  - Digital dermatitis is an infectious disease that causes lameness in dairy cattle,
      a primary welfare concern of the dairy industry. One of the common treatments for
      this painful hoof disease is through the application of an antibiotic bandage
      that must be removed following treatment. The objectives of this randomized
      clinical trial were to determine if topical application of tetracycline
      hydrochloride in a paste would be as therapeutically effective for the treatment
      of digital dermatitis as a powdered form of tetracycline hydrochloride held in
      place by a bandage, and to quantify pain associated with digital dermatitis
      lesions. Two hundred and fourteen Holstein cow hooves with digital dermatitis
      lesions were randomly assigned to 1 of 3 treatments: a tetracycline hydrochloride
      paste, tetracycline hydrochloride powder held in place with a bandage for 2 d, or
      a negative (untreated) control. Lesions were examined at 2 time periods: 3 to 7 d
      posttreatment and 8 to 12 d posttreatment to determine healing rates. Nociceptive
      thresholds were measured using a pressure algometer to quantify the pain at the
      lesion site. The tetracycline hydrochloride paste was as effective as the
      powdered bandage treatment in terms of healing rates, with 47.4 and 57.1% hooves
      healed at 8 to 12 d posttreatment, respectively. Both treatments were more
      effective than the control, in which no lesions healed 8 to 12 d following
      initial examination. Mean (+/-SE) nociceptive thresholds for active, healing, and
      healed lesions differed, with limb-withdrawal response occurring at 7.45 (+/
      0.67) kg, 12.84 (+/-1.85) kg, and censored to 25 kg (maximum value of algometer)
      of force applied, respectively. However, active lesions were not consistently
      associated with pain, as maximum force was tolerated when applied to 19% of
      active lesions, perhaps due to variability in stoicism between individual cattle
      or due to changes in pain during the progression of infection. In conclusion,
      tetracycline hydrochloride paste was as effective as tetracycline hydrochloride
      bandage, eliminating the need for bandage removal following treatment
      application. Digital lesions can be painful during both active and healing
      stages, suggesting the need for treatment and husbandry interventions for pain
      mitigation.

PMID- 24140337
TI  - Rapid, quantitative analysis of 3'- and 6'-sialyllactose in milk by flow
      injection analysis-mass spectrometry: screening of milks for naturally elevated
      sialyllactose concentration.
AB  - Non-protein-bound oligosaccharides are important bioactive components of cow
      milk, with potential human-health benefits such as stimulation of the growth of
      beneficial gut bacteria and defense against pathogens. In bovine milk, the
      majority of oligosaccharides are sialylated; 3'-sialyllactose (3'-N
      acetylneuraminyl-D-lactose; 3'-SL) is the predominant sialylated oligosaccharide,
      followed by 6'-sialyllactose (6'-N-acetylneuraminyl-D-lactose; 6'-SL). Both 3'-SL
      and 6'-SL have antimicrobial activity. As bovine milk products such as infant
      formula can be an important component of the human diet, and the concentrations
      of 3'-SL and 6'-SL are lower in bovine milk compared with human milk, we aimed to
      identify cows that naturally produce higher concentrations of sialyllactose in
      their milk. Milk from such cows could be used to produce foods with an increased
      sialyllactose content, potentially providing increased health benefits. We
      speculated that cows overexpressing 3'-SL and 6'-SL would exist at low frequency
      in the population and, to allow their efficient identification, we developed a
      novel assay for 3'-SL and 6'-SL utilizing flow-injection analysis-mass
      spectrometry, which could be used for high-throughput analysis of milk samples.
      We then determined 3'-SL and 6'-SL concentrations in milk samples from 15,507
      cows from Friesian, Jersey, and Friesian-Jersey crossbred animals. We found 329
      cows with concentrations of 3'-SL or 6'-SL >2-fold higher than the mean, 26 cows
      with concentrations of 3'-SL or 6'-SL >3-fold higher than the mean, and 1 cow
      with concentrations of 3'-SL >4-fold higher than the mean. Although these
      outliers were observed across the 3 groups of cows, breed had a strong effect on
      mean 3'-SL and 6'-SL concentrations.

PMID- 24140338
TI  - The influence of salt formation on electrostatic and compression properties of
      flurbiprofen salts.
AB  - Salt formation is an effective method of improving physicochemical properties of
      acidic and basic drugs. The selection of a salt form most suitable for drug
      development requires a well-designed screening strategy to ensure various issues
      are addressed in the early development stages. Triboelectrification of
      pharmaceutical powders may cause problems during processing such as segregation
      of components due to the effects of particle adhesion. However, very little work
      has been done on the effect of salt formation on triboelectrification properties.
      In this paper, salts of flurbiprofen were prepared by combining the drug with a
      selection of closely related amine counter ions. The aim of the work was to
      investigate the impact of the counter ion on electrostatic charge of the
      resultant salts to inform the salt selection process. The experimental results
      show the magnitude of charge and polarity of the flurbiprofen salts to be highly
      dependent on the type of counter ion selected for the salt formation.
      Furthermore, particle adhesion to the stainless steel surface of the shaking
      container and the salts' compression properties were measured. The formed salts
      had lower electrostatic charges, improved tabletability, and resulted in reduced
      adhesion of these powders compared with the parent drug. 

PMID- 24140339
TI  - Resistance to influenza A virus infection in transformed cell lines expressing an
      anti-PB2 monoclonal antibody.
AB  - The polymerase basic 2 (PB2) protein is one of four proteins that make up the
      influenza A virus replication complex, which is responsible for viral gene
      transcription and replication. To assess the antiviral potential of an anti-PB2
      monoclonal antibody that inhibits RNA transcription of influenza A viruses,
      Mardin-Darby canine kidney (MDCK) cells were transformed with two transgenes that
      encode the light and heavy chains of the monoclonal antibody. The transformed
      cell lines expressing this monoclonal antibody displayed resistance to several
      subtypes of influenza A virus infection. In the transformed cell lines infected
      with influenza A virus, the level of viral RNA transcription was decreased and
      the effective nuclear transportation of the PB2 protein was also inhibited. These
      results demonstrate that the anti-PB2 intrabody is potentially able to interfere
      with the effective nuclear transportation of PB2 protein, resulting in the
      observed resistance to influenza A virus infection in vitro. 

PMID- 24140340
TI  - Mesdc2 plays a key role in cell-surface expression of Lrp4 and postsynaptic
      specialization in myotubes.
AB  - Low-density lipoprotein receptor-related protein 4 (Lrp4) is essential for pre-
      and post-synaptic specialization at the neuromuscular junction (NMJ), an
      indispensable synapse between a motor nerve and skeletal muscle. Muscle-specific
      receptor tyrosine kinase MuSK must form a complex with Lrp4 to organize
      postsynaptic specialization at NMJs. Here, we show that the chaperon Mesdc2 binds
      to the intracellular form of Lrp4 and promotes its glycosylation and cell-surface
      expression. Furthermore, knockdown of Mesdc2 suppresses cell-surface expression
      of Lrp4, activation of MuSK, and postsynaptic specialization in muscle cells.
      These results suggest that Mesdc2 plays an essential role in NMJ formation by
      promoting Lrp4 maturation. 

PMID- 24140341
TI  - Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor
      4alpha.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) regulates liver type fatty acid
      binding protein (L-FABP) gene expression. Conversely as shown herein, L-FABP
      structurally and functionally also interacts with HNF4alpha. Fluorescence
      resonance energy transfer (FRET) between Cy3-HNF4alpha (donor) and Cy5-L-FABP
      (acceptor) as well as FRET microscopy detected L-FABP in close proximity (~80 A)
      to HNF4alpha, binding with high affinity Kd ~250-300 nM. Circular dichroism (CD)
      determined that the HNF4alpha/L-FABP interaction altered protein secondary
      structure. Finally, L-FABP potentiated transactivation of HNF4alpha in COS7
      cells. Taken together, these data suggest that L-FABP provides a signaling path
      to HNF4alpha activation in the nucleus.

PMID- 24140342
TI  - Albuminuria associated with CD2AP knockout mice is primarily due to dysfunction
      of the renal degradation pathway processing of filtered albumin.
AB  - Here we address the assumption that the massive intact albuminuria accompanying
      mutations of structural components of the slit diaphragm is due to changes in
      glomerular permeability. The increase in intact albumin excretion rate in Cd2ap
      knockout mice by >100-fold was not accompanied by equivalent changes in urine
      flow rate, glomerular filtration rate or increases in dextran plasma clearance
      rate, which demonstrates that changes in glomerular permeability alone could not
      account for the increase in intact albumin excretion. The albuminuria could be
      accounted for by inhibition of the tubule degradation pathway associated with
      degrading filtered albumin. There are remarkable similarities between these
      results and all types of podocytopathies in acquired and toxin-induced renal
      disease, and nephrotic states seen in mice with podocyte mutations. 

PMID- 24140343
TI  - Are amyloid fibrils molecular spandrels?
AB  - Amyloid-beta, the protein implicated in Alzheimer's disease, along with a number
      of other proteins, has been shown to form amyloid fibrils. Fibril forming
      proteins share no common primary structure and have little known function.
      Furthermore, all proteins have the ability to form amyloid fibrils under certain
      conditions as the fibrillar structure lies at the global free energy minimum of
      proteins. This raises the question of the mechanism of the evolution of the
      amyloid fibril structure. Experimental evidence supports the hypothesis that the
      fibril structure is a by-product of the forces of protein folding and lies
      outside the bounds of evolutionary pressures. 

PMID- 24140344
TI  - miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through
      targeting PREX2a.
AB  - MicroRNAs (miRNA) can regulate cancer cell proliferation and metastasis. Here, we
      show that miR-338-3p is down-regulated in metastatic tumor tissues compared to
      primary tumors, and that that miR-338-3p can inhibit cell proliferation by
      inducing cell cycle arrest, as well as restrain cell migration and invasion.
      PREX2a is confirmed as a direct target of miR-338-3p. Knockdown of PREX2a
      inhibits cell proliferation, migration and invasion through the PTEN/Akt pathway.
      miR-338-3p-dependent inhibition of proliferation and invasion can be rescued by
      PREXa. Overall, this study demonstrates that miR-338-3p affects the PTEN/Akt
      pathway by down-regulating PREX2a. This newly identified function of miR-338-3p
      provides novel insights into neuroblastoma and may foster therapeutic
      applications. 

PMID- 24140346
TI  - The multiple forms of bovine seminal ribonuclease: structure and stability of a C
      terminal swapped dimer.
AB  - Bovine seminal ribonuclease (BS-RNase) acquires an interesting anti-tumor
      activity associated with the swapping on the N-terminal. The first direct
      experimental evidence on the formation of a C-terminal swapped dimer (C-dimer)
      obtained from the monomeric derivative of BS-RNase, although under non-native
      conditions, is here reported. The X-ray model of this dimer reveals a quaternary
      structure different from that of the C-dimer of RNase A, due to the presence of
      three mutations in the hinge peptide 111-116. The mutations increase the hinge
      peptide flexibility and decrease the stability of the C-dimer against
      dissociation. The biological implications of the structural data are also
      discussed. 

PMID- 24140345
TI  - Rim15-dependent activation of Hsf1 and Msn2/4 transcription factors by direct
      phosphorylation in Saccharomyces cerevisiae.
AB  - Rim15 kinase, a downstream effector of PKA and TORC1 signaling pathways,
      initiates the quiescent program upon nutrient starvation via induction of genes
      whose expression depends on transcription factors Msn2, Msn4, and Gis1. Here, we
      demonstrate that Rim15 also induces expression of Hsf1 target genes upon glucose
      depletion by both transcriptional activation and stabilization of the
      transcripts. Rim15 phosphorylates Hsf1 in vitro, suggesting that Rim15 might
      directly activate Hsf1. In addition, Igo1 and Igo2, Rim15 substrate proteins
      involved in mRNA stabilization, regulate mRNA levels of Hsf1 target genes. We
      also show that Rim15 can phosphorylate Msn2, but not Gis1, in vitro, implying
      different mechanisms for the activation of these transcription factors. 

PMID- 24140347
TI  - PPARalpha regulates the production of serum Vanin-1 by liver.
AB  - The membrane-bound Vanin-1 pantetheinase regulates tissue adaptation to stress.
      We investigated Vnn1 expression and its regulation in liver. Vnn1 is expressed by
      centrolobular hepatocytes. Using novel tools, we identify a soluble form of Vnn1
      in mouse and human serum and show the contribution of a cysteine to its catalytic
      activity. We show that liver contributes to Vanin-1 secretion in serum and that
      PPARalpha is a limiting factor in serum Vnn1 production. Functional PPRE sites
      are identified in the Vnn1 promoter. These results indicate that serum Vnn1 might
      be a reliable reporter of PPARalpha activity in liver. 

PMID- 24140349
TI  - Electrochemical treatment of iopromide under conditions of reverse osmosis
      concentrates--elucidation of the degradation pathway.
AB  - Application of reverse osmosis for the reuse of treated wastewater on the one
      hand offers a way to provide high quality effluent waters. On the other hand
      reverse osmosis concentrates exhibiting highly concentrated contaminants are
      produced simultaneously. Electrochemical treatment of those concentrates is
      regarded as one possible answer to the problem of their disposal into surface
      waters. Nevertheless, due to the diversity of direct and indirect degradation
      processes during electrolysis, special care has to be taken about the formation
      of toxic transformation products (TPs). In this study the electrochemical
      transformation of the X-ray contrast medium iopromide was investigated as a
      representative of biologically persistent compounds. For this purpose, anodic
      oxidation at boron doped diamond as well as cathodic reduction using a platinum
      electrode were considered. Kinetic analyses revealed a transformation of 100 MUM
      iopromide with first order kinetic constants between 0.6 and 1.6 * 10(-4) s(-1)
      at the beginning and a subsequent increase of the reaction order due to the
      influence of secondary oxidants formed during electrolysis. Mineralization up to
      96% was achieved after about 7.5 h. At shorter treatment times several
      oxidatively and reductively formed transformation products were detected, whereas
      deiodinated iopromide represented the major fraction. Nevertheless, the latter
      exhibited negligible toxicological relevance according to tests on vibrio
      fisheri. Additional experiments utilizing a divided cell setup enabled the
      elucidation of the transformation pathway, whereas emerging TPs could be
      identified by means of high resolution mass spectrometry and MS(n)
      fragmentations. During electrolysis the iodine released from Iopromide was found
      to 90% as iodide and to 10% as iodate even in the open cell experiments, limiting
      the potential formation of toxic iodo-disinfection by-products. Chlorinated TPs
      were not found.

PMID- 24140348
TI  - Glypican-3 antibodies: a new therapeutic target for liver cancer.
AB  - Glypican-3 (GPC3) is an emerging therapeutic target in hepatocellular carcinoma
      (HCC), even though the biological function of GPC3 remains elusive. Currently
      human (MDX-1414 and HN3) and humanized mouse (GC33 and YP7) antibodies that
      target GPC3 for HCC treatment are under different stages of preclinical or
      clinical development. Humanized mouse antibody GC33 is being evaluated in a phase
      II clinical trial. Human antibodies MDX-1414 and HN3 are under different stages
      of preclinical evaluation. Here, we summarize current evidence for GPC3 as a new
      target in liver cancer, discuss both its oncogenic function and its mode of
      actions for current antibodies, and evaluate potential challenges for GPC3
      targeted anti-cancer therapies. 

PMID- 24140350
TI  - A novel methodology to quantify nitrous oxide emissions from full-scale
      wastewater treatment systems with surface aerators.
AB  - The quantification of nitrous oxide (N2O) emissions from open-surface wastewater
      treatment systems with surface aerators is difficult as emissions from the
      surface aerator zone cannot be easily captured by floating hoods. In this study,
      we propose and demonstrate a novel methodology to estimate N2O emissions from
      such systems through determination of the N2O transfer coefficient (kLa) induced
      by surface aerators based on oxygen balance for the entire system. The
      methodology is demonstrated through its application to a full-scale open
      oxidation ditch wastewater treatment plant with surface aerators. The estimated
      kLa profile based on a month-long measurement campaign for oxygen balance,
      intensive monitoring of dissolved N2O profiles along the oxidation ditch over a
      period of four days, together with mathematical modelling, enabled to determine
      the N2O emission factor from this treatment plant (0.52 +/- 0.16%). Majority of
      the N2O emission was found to occur in the surface aerator zone, which would be
      missed if the gas hood method was applied alone.

PMID- 24140351
TI  - Presence and transport of the antimicrobials triclocarban and triclosan in a
      wastewater-dominated stream and freshwater environment.
AB  - The presence of the antimicrobials triclocarban (TCC) and triclosan (TCS)in
      Fountain Creek, a wastewater-dominated stream, and the Arkansas River, Colorado,
      USA was measured in the surface water, suspended sediments, and bed sediments
      during spring runoff (high flow) and summer base flow (low flow) conditions.
      Fountain Creak is a tributary of the Arkansas River. Passive polar organic
      chemical integrative samplers (POCIS) were used along with active sampling (water
      grab samples) to measure and TCS concentrations in these surface waters. The
      concentration of TCC and TCS, based on POCIS measurements, ranged from 4.5 to
      47.3 ng/L and 3.9 to 28.3 ng/L, respectively, at the five sample sites monitored
      in this study under both flow conditions. The range of concentrations of TCC and
      TCS in suspended sediments was 0.7-57.3 ng/g and 0.7-13.3 ng/g, respectively, and
      was closely tied to the quantity of organic carbon in the suspended sediment,
      which ranged from 1.6 to 14.5%. The quantity of organic carbon in suspended
      sediment during the summer base flow was influenced by runoff from the burn area
      of a large forest fire that occurred between the two sampling periods. The
      primary transport mechanism of TCC and TCS in these surface waters was in the
      dissolved phase, with 64-99% of TCC and 68-99% of TCS transported in the
      dissolved phase. The total amount of TCS and TCC in bed-sediments was relatively
      low, with the maximum amount at any one site being 0.38 +/- 0.15 ng/g TCS and
      4.09 +/- 5.26 ng/g TCC. Fountain Creek contributed up to 76% and 69% of the TCC
      and TCS, respectively, that is transported directly below its confluence with
      Arkansas River. Fountain Creek drained approximately 3.0 g/day TCS (in spring),
      2.9 g/day TCS (in summer) and 1.9 g/day TCC (in spring), 2.0 g/day TCC (in
      summer) into the Arkansas River, which suggests consistent input of TCC and TCS
      into Fountain Creek, such as in discharge of treated wastewater that is
      independent of changing creek flow conditions.

PMID- 24140352
TI  - Partial nitritation and o-cresol removal with aerobic granular biomass in a
      continuous airlift reactor.
AB  - Several chemical industries produce wastewaters containing both, ammonium and
      phenolic compounds. As an alternative to treat this kind of complex industrial
      wastewaters, this study presents the simultaneous partial nitritation and o
      cresol biodegradation in a continuous airlift reactor using aerobic granular
      biomass. An aerobic granular sludge was developed in the airlift reactor for
      treating a high-strength ammonium wastewater containing 950 +/- 25 mg N-NH4(+) L(
      1). Then, the airlift reactor was bioaugmented with a p-nitrophenol-degrading
      activated sludge and o-cresol was added progressively to the ammonium feed to
      achieve 100 mg L(-1). The results showed that stable partial nitritation and full
      biodegradation of o-cresol were simultaneously maintained obtaining a suitable
      effluent for a subsequent anammox reactor. Moreover, two o-cresol shock-load
      events with concentrations of 300 and 1000 mg L(-1) were applied to assess the
      capabilities of the system. Despite these shock load events, the partial
      nitritation process was kept stable and o-cresol was totally biodegraded.
      Fluorescence in situ hybridization technique was used to identify the
      heterotrophic bacteria related to o-cresol biodegradation and the ammonia
      oxidising bacteria along the granules.

PMID- 24140353
TI  - Pharmacokinetics, biocompatibility and bioavailability of a controlled release
      monoclonal antibody formulation.
AB  - The sustained and localized delivery of monoclonal antibodies has become highly
      relevant, because of the increasing number of investigated local delivery
      applications in recent years. As the local delivery of antibodies is associated
      with high technological hurdles, very few successful approaches have been
      reported in the literature so far. Alginate-based delivery systems were
      previously described as promising sustained release formulations for monoclonal
      antibodies (mAbs). In order to further investigate their applicability, a single
      dose animal study was conducted to compare the biocompatibility, the
      pharmacokinetics and the bioavailability of a human monoclonal antibody liquid
      formulation with two alginate-based sustained delivery systems after subcutaneous
      administration in rats. 28 days after injection, the depot systems were still
      found in the subcutis of the animals. A calcium cross-linked alginate
      formulation, which was injected as a hydrogel, was present as multiple
      compartments separated by subcutaneous tissue. An in situ forming alginate
      formulation was recovered as a single compact and cohesive structure. It can be
      assumed that the multiple compartments of the hydrogel formulation led to almost
      identical pharmacokinetic profiles for all tested animals, whereas the compact
      nature of the in situ forming system resulted in large interindividual variations
      in pharmacokinetics. As compared to the liquid formulation the hydrogel
      formulations led to lower mAb serum levels, and the in situ forming system to a
      shift in the time to reach the maximum mAb serum concentration (Tmax) from 2 to 4
      days. Importantly, it was shown that after 28 days only marginal amounts of
      residual mAb were present in the alginate matrix and in the tissue at the
      injection site indicating nearly complete release. In line with this finding,
      systemic drug bioavailability was not affected by using the controlled release
      systems. This study successfully demonstrates the suitability and underlines the
      potential of polyanionic systems for local and controlled mAb delivery.

PMID- 24140354
TI  - Comparison of methane production potential, biodegradability, and kinetics of
      different organic substrates.
AB  - The methane production potential, biodegradability, and kinetics of a wide range
      of organic substrates were determined using a unified and simple method. Results
      showed that feedstocks that contained high energy density and easily degradable
      substrates exhibited high methane production potential and biodegradability.
      Lignocellulosic biomass with high content of fibrous compositions had low methane
      yield and biodegradability. Feedstocks with high lignin content (>= 15%, on a TS
      basis) had low first-order rate constant (0.05-0.06 1/d) compared to others. A
      negative linear correlation between lignin content and experimental methane yield
      (or biodegradability) was found for lignocellulosic and manure wastes. This could
      be used as a fast method to predict the methane production potential and
      biodegradability of fiber-rich substrates. The findings of this study provided a
      database for the conversion efficiency of different organic substrates and might
      be useful for applications of biomethane potential assay and anaerobic digestion
      in the future.

PMID- 24140355
TI  - Comparative life cycle assessment of biodiesel from algae and jatropha: a case
      study of India.
AB  - Algae and jatropha, two types of promising and unconventional biomass, are
      investigated in this study for large-scale production of biodiesel. The aim is to
      evaluate the potential advantages and the magnitude of closeness of life cycle
      balances between these two biodiesel pathways compared to fossil diesel, by
      taking into account possible uncertainties. The geographical location of this
      study is India with a prospect of utilizing available wastelands in southern
      regions. The results indicate that the environmental performance of algal
      biodiesel is comparable to that of jatropha biodiesel. Both show significant GHG
      emission and fossil energy depletion reductions which are in the range of 36-40
      and 10-25% respectively compared to fossil diesel in the studied geographic
      context. 

PMID- 24140356
TI  - Achieving partial denitrification with sludge fermentation liquid as carbon
      source: the effect of seeding sludge.
AB  - The partial denitrification (nitrate to nitrite) has been a promising way for
      nitrate wastewater treatment combined with ANAMMOX system subsequently. This work
      investigated the effect of seeding sludge on partial denitrification by using
      sludge fermentation liquid as carbon source, with the sludge taken from:
      anoxic/oxic reactor (SA), anaerobic-anoxic-oxic reactor (SA-A-O) and alternately
      anaerobic sludge fermentation coupling anoxic denitrification reactor (SA-A). The
      results showed that transient accumulation of nitrite was observed in SA and SA-A
      O. However, at the initial nitrate concentration of 30 mg/L, a high nitrite of
      20.91 +/- 0.52 mg/L was accumulated under complete nitrate reduction in the SA-A
      system, which indicated that partial denitrification could be realized.
      Furthermore, as much as 80% nitrate-to-nitrite transformation ratio (NTR) was
      achieved in a 108-day operation with inoculating SA-A, which illustrated the
      stability of partial denitrification under long-term operation.

PMID- 24140357
TI  - Isolation and heterotrophic cultivation of mixotrophic microalgae strains for
      domestic wastewater treatment and lipid production under dark condition.
AB  - Cultivating microalgae heterotrophically could overcome the light dependency, and
      thus increase the yield of microalgal lipid per unit area. In this study, three
      newly isolated strains of microalgae (Scenedesmus sp. ZTY2, Scenedesmus sp. ZTY3
      and Chlorella sp. ZTY4) from a domestic wastewater treatment plant were
      heterotrophically cultivated in domestic wastewater with no illumination. During
      the cultivation, the algal densities of Scenedesmus species and Chlorella species
      were increased by 203.0% and 60.5% comparing with the initial densities,
      respectively. After 11-day cultivation, the lipid contents of Scenedesmus sp.
      ZTY2, Scenedesmus sp. ZTY3 and Chlorella sp. ZTY4 reached 69.1%, 55.3% and 79.2%,
      respectively. The DOC removal efficiencies of these three strains were 63.4%,
      52.9% and 64.4%, and the biomass yield were 1.65, 1.98 and 2.31mg biomass/mg DOC,
      respectively. This is the first report about the heterotrophic cultivation of
      microalgae strains for domestic wastewater treatment and lipid production under
      dark condition.

PMID- 24140358
TI  - Improved volatile fatty acid and biomethane production from lipid removed
      microalgal residue (LRMUAR) through pretreatment.
AB  - Renewable energy from lipid removed microalgal residues (LRMUARs) serves as a
      promising tool for sustainable development of the microalgal biodiesel industry.
      Hence, in this study, LRMUAR from Ettlia sp. was characterized for its physico
      biochemical parameters, and applied to various pretreatment to increase the
      biodegradability and used in batch experiments for the production of volatile
      fatty acids (VFA) and biomethane. After various pretreatments, the soluble
      organic matters were increased at a maximum of 82% in total organic matters in
      alkali-autoclaved sample. In addition, VFA and methane production was enhanced by
      30% and 40% in alkali-sonicated and alkali-autoclaved samples, respectively.
      Methane heating value was recovered at maximum of 6.6 MJ kg(-1)VS in alkali
      autoclaved conditions with comparison to non-pretreated samples. The pretreatment
      remarkably improved LRMUAR solubilization and enhanced VFA and biomethane
      production, which holds immense potential to eventually reduce the cost of algal
      biodiesel.

PMID- 24140359
TI  - Extrusion of xylans extracted from corn cobs into biodegradable polymeric
      materials.
AB  - Solvent casting technique, which comprises multiple energy demanding steps
      including the dissolution of a polymer in a solvent followed by the evaporation
      of the solvent from the polymer solution, is currently the main technique for the
      production of xylan based polymeric materials. The present study shows that
      sufficient water content renders arabinoglucuronoxylan (AGX) polymers extrudable,
      enabling the production of AGX based polymeric materials in a single step via
      extrusion, which is economically advantageous to solvent casting process for mass
      production. AGX polymers with water content of 27% were found to yield extrudates
      at an extrusion temperature of 90 degrees C. The extruded strips showed very good
      mechanical properties with an ultimate tensile strength of 76 +/- 6 MPa and
      elongation at break value of 35 +/- 8%, which were superior to the mechanical
      properties of the strips obtained from polylactic acid.

PMID- 24140360
TI  - Two fluorogenic substrates for purine nucleoside phosphorylase, selective for
      mammalian and bacterial forms of the enzyme.
AB  - Two nontypical nucleosides, 7-beta-D-ribosyl-2,6-diamino-8-azapurine and 8-beta-D
      ribosyl-2,6-diamino-8-azapurine, have been found to exhibit moderately good, and
      selective, substrate properties toward calf and bacterial (Escherichia coli)
      forms of purine nucleoside phosphorylase (PNP). The former compound is
      effectively phosphorolysed by calf PNP and the latter by PNP from E. coli. Both
      compounds are fluorescent with lambda(max) ~ 425 to 430 nm, but the reaction
      product, 2,6-diamino-8-azapurine, emits in a different spectral region
      (lambda(max) ~ 363 nm) with nearly 40% yield, providing a strong fluorogenic
      effect at 350 to 360 nm.

PMID- 24140363
TI  - National healthcare initiatives and pursuit of wrist surgery innovations: a
      report of the 2011-2012 Sterling Bunnell Traveling Fellow.
AB  - Every year since 1982, the American Society for Surgery of the Hand has sponsored
      a young member as its Bunnell Traveling Fellow. Named eponymously for the late
      physician and father of hand surgery, the Sterling Bunnell Traveling Fellowship
      enables young hand surgeons to foster national and international relationships
      that contribute to their higher learning and advance the principles of
      scholarship by improving treatment of hand and upper extremity disorders. This
      report is an account of the experiences and insights I gained while exploring
      national health care initiatives and wrist surgery innovations. 

PMID- 24140362
TI  - Collagenase clostridium histolyticum for dupuytren contracture: patterns of use
      and effectiveness in clinical practice.
AB  - PURPOSE: To collect data on the real-world effectiveness of collagenase
      clostridium histolyticum (CCH) during its first year of use following U.S. Food
      and Drug Administration approval and compare those results with clinical trial
      efficacy data. METHODS: This retrospective chart review was conducted at 10 U.S.
      community and academic practice sites with major experience using CCH. Charts of
      patients treated with CCH between February and December 2010 were abstracted, and
      anonymized data were analyzed. Clinical use, including number of injections per
      cord and effectiveness outcomes (joint contracture and range of motion) were
      compared with results from 2 registration trials. RESULTS: Data were collected
      from 501 patients (74% male; 48% employed; mean [SD] age, 65 [10] y); 463
      patients had sufficient data for analysis. We found that 1.08 CCH injections were
      used per treated joint, compared with a mean of 1.7 injections in registration
      trials. Ninety-three percent of joints received only 1 injection. The mean (SD)
      number of visits per injection was 2.92 (1.0). Mean (SD) contracture was reduced
      by 75% from 49 degrees  (21) at baseline to 12 degrees  (17), similar to the 71%
      to 79% reduction in clinical trials. Mean (SD) range of motion was improved by 37
      degrees  from 44 degrees  (20) at baseline to 81 degrees  (14), similar to the
      increase of 35 degrees  and 37 degrees  in the 2 clinical trials; and 67% of
      first injections resulted in full correction to 0 degrees  to 5 degrees ,
      compared with the clinical trial rate of 39%. CONCLUSIONS: Despite a lower
      injection rate, correction of joint contracture and range of motion was similar
      to findings from clinical trials. Effectiveness reports using this kind of
      surveillance design could provide patients, physicians, and payers with the
      information needed to make better treatment and reimbursement decisions. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24140364
TI  - Response of dupuytren fibroblasts to different oxygen environments.
AB  - PURPOSE: It is thought that local ischemia and oxygen radicals are responsible
      for fibroblast-to-myofibroblast cell transformation and proliferation. We
      hypothesized that hypoxia could differentially activate the contractility of
      fibroblasts from normal human palmar fascia and from fibroblasts-myofibroblasts
      of Dupuytren cords. METHODS: Normal palmar fascia from 5 patients with carpal
      tunnel syndrome and Dupuytren cords from 5 patients were harvested. Cells were
      cultured from all tissue samples, and collagen lattices were prepared containing
      these cells. Oxygen treatment subgroups were created and incubated under hypoxic
      (1% O(2), 5% CO(2), and 94% N(2)), normoxic (21% O(2), 5% CO(2), and 74% N(2)),
      and hyperoxic (100% oxygen using 2.4 atm pressure twice a day for 7 d)
      conditions. After 7 days, each subgroup was photographed, and lattices were
      released from dishes. Postrelease photographs were taken immediately, 5 minutes
      after release, and after 1 hour. Areas of the lattices at each time point were
      calculated using MetaMorph software. Actin staining and live/dead cell analysis
      was performed. Linear repeated measures analysis of variance was used for data
      analysis given that contraction levels were measured over 3 distinct time points.
      RESULTS: We found a statistically significant difference between normal samples
      and Dupuytren samples in mean contraction levels over time. There was no
      statistically significant difference between tissue groups over the 3 time
      periods based on the oxygen treatment received. CONCLUSIONS: Our results showed a
      greater degree of contractility in Dupuytren disease cells than normal
      fibroblasts. However, the contraction in either group was not affected by oxygen
      level. Future in vivo research is needed to better understand the nature of
      pathophysiology of Dupuytren disease.

PMID- 24140365
TI  - Tendon-bone graft for tendinous mallet fingers following failed splinting.
AB  - PURPOSE: To describe and assess a surgical technique for the treatment of
      tendinous mallet fingers after failed conservative treatment. METHODS: From
      January 2010 to March 2012, 28 tendinous mallet fingers in 28 patients were
      treated. All patients had greater than 25 degrees  extensor lags after 6 to 8
      weeks of splinting. Four patients had a second trial of splinting, which also
      failed. A tendon-bone graft, taken from the extensor carpi radialis brevis and
      the third metacarpal base, was used for reconstruction. The mean time between the
      injury and operation was 74 days. The mean preoperative extension lag was 34
      degrees . Five patients reported pain in the distal interphalangeal joint. At the
      final follow-up, patients rated the level of pain on the distal interphalangeal
      and wrist joints using a visual analog scale. Joint motion was graded with the
      Crawford criteria. Hand function was assessed with the Disabilities of the Arm,
      Shoulder, and Hand questionnaire. Patients reported on their satisfaction based
      on the Michigan Hand Outcomes Questionnaire. RESULTS: Bone healing was achieved
      in all patients at a mean of 5 weeks. Position of bone graft was maintained until
      bone healing was evident in all cases. At the mean follow-up period of 15 months,
      nail deformity was not noted. No patient reported pain on the distal
      interphalangeal joint or wrist. The mean residual extension lag of the distal
      interphalangeal joints was 4 degrees . The results showed that 24 digits were
      excellent and 4 were good based on the Crawford criteria. The Disabilities of the
      Arm, Shoulder, and Hand scores averaged 1, and 27 patients were satisfied with
      appearance of the hand. One patient sometimes felt uncomfortable regarding the
      appearance. CONCLUSIONS: A tendon-bone graft is a useful and reliable technique
      for the treatment of tendinous mallet fingers after failed splinting. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24140366
TI  - Nursing students' and preceptors' perceptions of using a revised assessment form
      in clinical nursing education.
AB  - Assessment of students' learning is a crucial question when great changes occur
      in the higher education sector. One such educational reform is the Bologna
      declaration, the requirements of which have resulted in significant modifications
      in documents as assessment forms for clinical education. The aim of this study
      was to investigate students' and preceptors' perceptions of using the revised
      version of an assessment form, the AssCE form. Using convenience sampling, a
      questionnaire survey was completed by 192 nursing students and 101 preceptors.
      Most of the participants found that the revised AssCE form was possible to use
      during different years of the programme, and factors in the AssCE form were
      possible to combine with learning outcomes in the course syllabus. Most
      participants perceived that the scale added to each factor facilitated the
      assessment dialogue and offered possibilities to illustrate the students'
      development during clinical periods. Findings also showed that students were most
      often prepared with self-assessment before the assessment discussions. More
      information about the use of the AssCE form, also in combination with learning
      outcomes in the course syllabus, may further support the use of the form and
      contribute to students' development during clinical practice.

PMID- 24140367
TI  - Resolving the enigma of the mesoamerican nephropathy: a research workshop
      summary.
AB  - The First International Research Workshop on Mesoamerican Nephropathy (MeN) met
      in Costa Rica in November 2012 to discuss how to establish the extent and degree
      of MeN, examine relevant causal hypotheses, and focus efforts to control or
      eliminate the disease burden. MeN describes a devastating epidemic of chronic
      kidney disease of unknown origin predominantly observed among young male
      sugarcane cutters. The cause of MeN remains uncertain; however, the strongest
      hypothesis pursued to date is repeated episodes of occupational heat stress and
      water and solute loss, probably in combination with other potential risk
      factor(s), such as nonsteroidal anti-inflammatory drug and other nephrotoxic
      medication use, inorganic arsenic, leptospirosis, or pesticides. At the research
      workshop, clinical and epidemiologic case definitions were proposed in order to
      facilitate both public health and research efforts. Recommendations emanating
      from the workshop included measuring workload, heat, and water and solute loss
      among workers; quantifying nephrotoxic agents in drinking water and food; using
      biomarkers of early kidney injury to explore potential causes of MeN; and
      characterizing social and working conditions together with methods for valid data
      collection of exposures and personal risk factors. Advantages and disadvantages
      of different population study designs were detailed. To elucidate the etiology of
      MeN, multicountry studies with prospective cohort design, preferably integrating
      an ecosystem health approach, were considered the most promising. In addition,
      genetic, experimental, and mechanistic methods and designs were addressed,
      specifically the need for kidney biopsy analysis, studies in animal models,
      advances in biomarkers, genetic and epigenetic studies, a common registry and
      repository of biological and demographic data and/or specimens, and other areas
      of potential chronic kidney disease experimental research. Finally, in order to
      improve international collaboration on MeN, workshop participants agreed to
      establish a research consortium to link these Mesoamerican efforts to other
      efforts worldwide. 

PMID- 24140368
TI  - Hemodialysis arteriovenous fistula created from the posterior tibial artery and a
      saphenous vein branch.

PMID- 24140369
TI  - The DOPPS practice monitor for U.S. dialysis care: update on trends in anemia
      management 2 years into the bundle.

PMID- 24140370
TI  - Tuberculous lymphadenitis in a dialysis patient diagnosed by 18
      fluorodeoxyglucose positron emission tomography and IFN-gamma release assay.

PMID- 24140371
TI  - Laser welding in penetrating keratoplasty and cataract surgery in pediatric
      patients: early results.
AB  - PURPOSE: To evaluate the efficacy of diode laser welding to close corneal wounds
      in penetrating keratoplasty (PKP) and cataract surgery in pediatric patients.
      SETTING: Ophthalmology Department, Bambino Gesu Children's Hospital, Rome, Italy.
      DESIGN: Prospective observational study. METHODS: Patients had surgery for
      congenital cataract (Group 1) or femtosecond laser-assisted PKP (Group 2). The
      surgery was followed by corneal wound closure using diode laser welding of the
      stroma. In Group 1, no standard suturing was used. In Group 2, the donor button
      was sutured onto the recipient using 8 single nylon sutures or a 10-0 nylon
      running suture (12 passages). Laser welding was then used as an adjunct to the
      traditional suturing procedure. RESULTS: Group 1 comprised 7 eyes (7 patients;
      mean age 8.1 years +/- 5.3 [SD], range 1 to 15 years) and Group 2, 5 eyes (5
      patients; mean age 10.6 +/- 3.3 years, range 6 to 15 years). The adhesion of the
      laser-welded tissues was perfect; there were no collateral effects, and
      restoration of the treated tissues was optimum. Seidel testing showed no wound
      leakage during the follow-up. Postoperative astigmatism did not change
      significantly from the first day after cataract surgery and shifted moderately 3
      months after PKP. CONCLUSION: Laser welding of corneal tissue appeared to be safe
      and effective in children for whom a sutureless surgical procedure is important
      to reduce the use of anesthesia for suture management, prevent endophthalmitis,
      and improve the antiamblyopic effect.

PMID- 24140372
TI  - Effect of heparin coating of a foldable intraocular lens on inflammation and
      capsular bag performance after cataract surgery.
AB  - PURPOSE: To evaluate the effect of a heparin-coated foldable intraocular lens
      (IOL) on postoperative flare in high-risk patients. SETTING: Vienna Institute for
      Research in Ocular Surgery, Department of Ophthalmology, Hanusch Hospital,
      Vienna, Austria. DESIGN: Randomized clinical trial. METHODS: This study included
      patients with diabetes mellitus (DM), pseudoexfoliation syndrome (PXF), or both
      scheduled for cataract surgery in both eyes. One eye received a coated IOL
      (Polylens EC-1YH PAL) and the other eye, an uncoated control IOL (Polylens EC-1Y
      PAL). Aqueous flare measurements were taken using a laser flare meter (FM-600,
      Kowa) preoperatively and 1 hour, 1 day, 3 weeks, and 3 months postoperatively.
      Visual acuity and anterior (ACO) and posterior (PCO) capsule opacification were
      assessed, and IOL centration and tilt were measured with a Purkinje meter.
      RESULTS: Eighty eyes of 40 patients were included in the study; 64 eyes of 32
      patients completed the study. The mean flare values (photons/ms) preoperatively
      and 1 hour, 1 day, 3 weeks, and 3 months postoperatively were 6.98 +/- 3.71 (SD),
      19.14 +/- 18.90, 16.62 +/- 25.33, 10.33 +/- 9.70, 8.74 +/- 4.64, respectively,
      with the coated IOL and 8.65 +/- 5.73, 22.08 +/- 16.23, 13.44 +/- 13.71, 7.50 +/-
      4.11, and 7.03 +/- 3.70, respectively, with the control IOL. No significant
      differences were found in flare, visual acuity, ACO, PCO, tilt, or centration
      between the coated IOL and the control IOL at any timepoint. CONCLUSION: No
      significant differences in flare or capsule performance were found between the
      coated IOL and control IOL.

PMID- 24140373
TI  - Laser-assisted cataract surgery following insertion of a pupil expander for
      management of complex cataract and small irregular pupil.
AB  - We report a case in which laser-assisted cataract surgery was performed safely
      and successfully following manual division of posterior synechiae and mechanical
      dilation of the pupil with a Malyugin ring in a patient with an irregular, small
      stuck-down pupil.

PMID- 24140374
TI  - Reverse pupillary block associated with pigment dispersion syndrome after in-the
      bag intraocular lens implantation.
AB  - A 61-year-old man with high myopia who had received a systemic alpha1A
      adrenoceptor antagonist had phacoemulsification and in-the-bag intraocular lens
      implantation in the right eye. One day postoperatively, marked pigment dispersion
      in the anterior chamber, posterior bowing of the iris, and iridodonesis were
      noted associated with a subsequent elevation in intraocular pressure (IOP).
      Pharmacological pupil dilation was effective in reducing pigment dispersion and
      IOP, and laser peripheral iridotomy was performed to alleviate posterior bowing
      of the iris. We hypothesize that dynamic changes in the aqueous humor flow by
      cataract surgery and latent flaccidity of the iris due to the systemic alpha1A
      adrenoceptor antagonist caused reverse pupillary block. High myopia may be
      another risk factor for this complication.

PMID- 24140375
TI  - Effect of preoperative corneal astigmatism orientation on results with a toric
      intraocular lens.
AB  - PURPOSE: To compare the Acrysof IQ toric intraocular lens (IOL) and the Acrysof
      IQ aspheric nontoric IOL and evaluate the effect of preoperative corneal
      astigmatism orientation on results. SETTING: Department of Ophthalmology, Faculty
      of Medicine, University of Tsukuba, Ibaraki, Japan. DESIGN: Comparative case
      series. METHODS: This retrospective chart review comprised patients with cataract
      and preoperative corneal astigmatism between 1.0 diopter (D) and 2.5 D having
      toric IOL (toric group) or aspheric nontoric IOL (nontoric group) implantation.
      Eyes were grouped depending on the preoperative axis of corneal astigmatism; that
      is, with the rule (WTR), against the rule (ATR), and oblique. Preoperative and
      postoperative analyses included uncorrected (UDVA) and corrected (CDVA) distance
      visual acuities and cylindrical power preoperatively and 3 months
      postoperatively. RESULTS: The postoperative CDVA was not significantly different
      between the 2 IOLs; however, the postoperative UDVA was significantly better in
      the toric group than in the nontoric group (P<.0001). The postoperative residual
      cylindrical power was significantly smaller in the toric group (P<.0001). In eyes
      with ATR and oblique astigmatism, the mean postoperative UDVA was significantly
      better in the toric group, whereas there were no differences between the 2 groups
      in patients with WTR astigmatism. CONCLUSIONS: There was significant improvement
      in postoperative cylinder and UDVA with toric IOLs compared with nontoric IOLs.
      With a superior corneal incision, the benefits of astigmatism correction with the
      toric IOL were more significant in patients with ATR and oblique astigmatism than
      in those with WTR astigmatism.

PMID- 24140376
TI  - Treating landfill gas hydrogen sulphide with mineral wool waste (MWW) and rod
      mill waste (RMW).
AB  - Hydrogen sulphide (H2S) gas is a major odorant at municipal landfills. The gas
      can be generated from different waste fractions, for example demolition waste
      containing gypsum based plaster board. The removal of H2S from landfill gas was
      investigated by filtering it through mineral wool waste products. The flow of gas
      varied from 0.3 l/min to 3.0 l/min. The gas was typical for landfill gas with a
      mean H2S concentration of ca. 4500 ppm. The results show that the sulphide gas
      can effectively be removed by mineral wool waste products. The ratios of the
      estimated potential for sulphide precipitation were 19:1 for rod mill waste (RMW)
      and mineral wool waste (MWW). A filter consisting of a mixture of MWW and RMW,
      with a vertical perforated gas tube through the center of filter material and
      with a downward gas flow, removed 98% of the sulfide gas over a period of 80
      days. A downward gas flow was more efficient in contacting the filter materials.
      Mineral wool waste products are effective in removing hydrogen sulphide from
      landfill gas given an adequate contact time and water content in the filter
      material. Based on the estimated sulphide removal potential of mineral wool and
      rod mill waste of 14 g/kg and 261 g/kg, and assuming an average sulphide gas
      concentration of 4500 ppm, the removal capacity in the filter materials has been
      estimated to last between 11 and 308 days. At the studied location the
      experimental gas flow was 100 times less than the actual gas flow. We believe
      that the system described here can be upscaled in order to treat this gas flow.

PMID- 24140377
TI  - Strategies for the enhancement of automobile shredder residues (ASRs) recycling:
      results and cost assessment.
AB  - With reference to the European regulation about the management of End-of-Life
      Vehicles (ELVs), Directive 2000/53/EC imposes the achievement of a recycling
      target of 85%, and 95% of total recovery by 2015. Over the last few years many
      efforts have been made to find solutions to properly manage the waste coming from
      ELVs with the aim of complying with the targets fixed by the Directive. This
      paper focuses on the economical evaluation of a treatment process, that includes
      physical (size and density), magnetic and electrical separations, performed on
      the light fraction of the automobile shredder residue (ASR) with the aim of
      reducing the amount of waste to dispose of in a landfill and enhancing the
      recovery of valuable fractions as stated by the EU Directive. The afore mentioned
      process is able to enhance the recovery of ferrous and non-ferrous metals of an
      amount equal to about 1% b.w. (by weight) of the ELV weight, and to separate a
      high energetic-content product suitable for thermal valorization for an amount
      close to (but not higher than) 10% b.w. of the ELV weight. The results of the
      economical assessment led to annual operating costs of the treatment ranging from
      300,000 ?/y to 350,000 ?/y. Since the considered plant treats about 13,500
      metrictons of ASR per year, this would correspond to an operating cost of
      approximately 20-25 ?/t. Taking into account the amount and the selling price of
      the scrap iron and of the non magnetic metal recovered by the process, thus
      leading to a gain of about 30 ?/t per ton of light ASR treated, the cost of the
      recovery process is balanced by the profit from the selling of the recovered
      metals. On the other hand, the proposed treatment is able to achieve the
      fulfillment of the targets stated by Directive 2000/53/EC concerning thermal
      valorization and reduce the amount of waste generated from ELV shredding to
      landfill.

PMID- 24140378
TI  - Combined Municipal Solid Waste and biomass system optimization for district
      energy applications.
AB  - Municipal Solid Waste (MSW) disposal has been a controversial issue in many
      countries over the past years, due to disagreement among the various stakeholders
      on the waste management policies and technologies to be adopted. One of the ways
      of treating/disposing MSW is energy recovery, as waste is considered to contain a
      considerable amount of bio-waste and therefore can lead to renewable energy
      production. The overall efficiency can be very high in the cases of co-generation
      or tri-generation. In this paper a model is presented, aiming to support decision
      makers in issues relating to Municipal Solid Waste energy recovery. The idea of
      using more fuel sources, including MSW and agricultural residue biomass that may
      exist in a rural area, is explored. The model aims at optimizing the system
      specifications, such as the capacity of the base-load Waste-to-Energy facility,
      the capacity of the peak-load biomass boiler and the location of the facility.
      Furthermore, it defines the quantity of each potential fuel source that should be
      used annually, in order to maximize the financial yield of the investment. The
      results of an energy tri-generation case study application at a rural area of
      Greece, using mixed MSW and biomass, indicate positive financial yield of
      investment. In addition, a sensitivity analysis is performed on the effect of the
      most important parameters of the model on the optimum solution, pinpointing the
      parameters of interest rate, investment cost and heating oil price, as those
      requiring the attention of the decision makers. Finally, the sensitivity analysis
      is enhanced by a stochastic analysis to determine the effect of the volatility of
      parameters on the robustness of the model and the solution obtained. 

PMID- 24140380
TI  - Does breastfeeding influence the risk of developing diabetes mellitus in
      children? A review of current evidence.
AB  - OBJECTIVE: The aim of this study was to perform a review to investigate the
      influence of breastfeeding as a protective agent against the onset of diabetes in
      children. SOURCES: non-systematic review of SciELO, LILACS, MEDLINE, Scopus, and
      VHL databases, and selection of the 52 most relevant studies. A total of 21
      articles, specifically on the topic, were analyzed (nine related to type 1
      diabetes and 12 to type 2 diabetes). DATA SYNTHESIS: The duration and exclusivity
      of breastfeeding, as well as the early use of cow's milk, have been shown to be
      important risk factors for developing diabetes. It is believed that human milk
      contains substances that promote the maturation of the immune system, which
      protect against the onset of type 1 diabetes. Moreover, human milk has bioactive
      substances that promote satiety and energy balance, preventing excess weight gain
      during childhood, thus protecting against the development of type 2 diabetes.
      Although the above mentioned benefits have not been observed by some researchers,
      inaccuracies on dietary habit reports during childhood and the presence of
      interfering factors have been considered responsible for the lack of
      identification of beneficial effects. CONCLUSION: Given the scientific evidence
      indicated in most published studies, it is believed that the lack of
      breastfeeding can be a modifiable risk factor for both type 1 and type 2
      diabetes. Strategies aiming at the promotion and support of breastfeeding should
      be used by trained healthcare professionals in order to prevent the onset of
      diabetes.

PMID- 24140379
TI  - Timing in resolution of left heart dilation according to the degree of mitral
      regurgitation in children with ventricular septal defect after surgical closure.
AB  - OBJECTIVE: Children with ventricular septal defects (VSD) can have chronic volume
      overload, which can result in changes of left heart echocardiographic parameters.
      To evaluate the changes before and after surgical closure, the children were
      divided into three groups according to the degree of mitral regurgitation (MR),
      and their echocardiographic characteristics were reviewed at serial follow-up
      after surgical closure. METHODS: The preoperative, and one-, three-, and 12-month
      postoperative echocardiographic data of 40 children who underwent surgical
      closure of VSD were retrospectively reviewed. Left ventricular end-diastolic
      volume (LVEDV), left ventricular end-diastolic dimension (LVEDD), left
      ventricular end-systolic dimension (LVESD), mitral valvular characteristics,
      including degree of MR and mitral valve annulus, and left atrial (LA)
      characteristics, including volume and dimensions, were observed. RESULTS:
      Preoperative LVEDV, LVEDD, LVESD, mitral valvular annulus, LA volume, and LA
      dimensions were significantly larger in children with MR. Additionally, there
      were significant decreases in LVEDV, LVEDD, LA volume, and LA dimensions at one,
      three, and 12 months postoperatively. The degree of MR also improved to a lower
      grade after surgical closure of the VSD without additional mitral valve repair.
      CONCLUSION: The echocardiographic parameters of left heart dilation and MR in
      children with VSD improved within the first year after surgical closure without
      additional mitral valve repair. Furthermore, in all of the patients with VSD,
      regardless of MR, LA dilation was reduced within three months after surgical
      closure of the VSD; however, LV and mitral valve annular dilatation decreased
      within 12 months.

PMID- 24140381
TI  - Evidence of underdiagnosis and markers of high blood pressure risk in children
      aged 6 to 13 years.
AB  - OBJECTIVE: To estimate the prevalence of high blood pressure (BP) in
      schoolchildren, as well as the reported frequency of previous measurements of BP
      in these children, and to identify high BP risk markers in the sample. METHODS:
      This was a cross-sectional study involving 794 children aged 6 to 13 years,
      enrolled in public elementary schools. A questionnaire was given to
      parents/guardians, consisting of perinatal, socioeconomic data, and information
      on previous measurements of BP in these children. Anthropometric measurements
      included weight, height, waist, hip, and arm and neck circumference, in addition
      to the three BP measurements. Classification of BP levels was carried out
      according to current international recommendations, established in 2004. RESULTS:
      The prevalence of high BP (hypertension or prehypertension) was 7%. Only 21.7% of
      children had previously undergone BP measurements. The odds ratio of high BP
      among children with and without overweight was 2.9 (95% CI=1.7 to 5.0, p<0.001).
      None of the anthropometric measurements was superior to the Z-score of BMI as a
      predictor of high BP. History of hypertension during pregnancy (p<0.001),
      prematurity (p=0.006), maternal hypertension (p=0.01), and paternal hypertension
      (p=0.008) were also correlated with the presence of high BP in children.
      CONCLUSIONS: Overweight and family history constitute the main risk markers of
      high BP in children. The low frequency of BP measurement in children observed in
      this municipality contributes to the underdiagnosis of the disease, with
      irreversible consequences for these individuals.

PMID- 24140382
TI  - Vitamin D deficiency (VDD): the culprit of cardiometabolic diseases?

PMID- 24140383
TI  - Effects of vitamin D supplementation on insulin resistance and cardiometabolic
      risk factors in children with metabolic syndrome: a triple-masked controlled
      trial.
AB  - OBJECTIVE: This triple-masked controlled trial aimed to assess the effects of
      vitamin D supplementation on insulin resistance and cardiometabolic risk factors
      in obese children and adolescents. METHODS: The study comprised 50 participants,
      aged 10 to 16 years, who were randomly assigned into two groups of equal number.
      In this 12-week trial, one group received oral vitamin D (300,000 IU) and the
      other group received placebo. Cardiometabolic risk factors, insulin resistance,
      and a continuous value of metabolic syndrome (cMetS) were determined. Statistical
      analysis was conducted after adjustment for covariate interactions. RESULTS:
      Overall, 21 patients in the vitamin D group and 22 in the placebo group completed
      the trial. No significant difference was observed in the baseline characteristics
      of the two groups. After the trial, in the vitamin D group, serum insulin and
      triglyceride concentrations, as well as HOM -IR and C-MetS decreased
      significantly, both when compared with the baseline and with the placebo group.
      No significant difference was observed when comparing total cholesterol, LDL-C,
      HDL-C, fasting blood glucose, and blood pressure. CONCLUSION: The present
      findings support the favorable effects of vitamin D supplementation on reducing
      insulin resistance and cardiometabolic risk factors in obese children.

PMID- 24140384
TI  - Wear and degradation on retrieved zirconia femoral heads.
AB  - Zirconia femoral heads retrieved from patients after different implantation
      periods (up to 13 years) were analysed using vertical scanning interferometry,
      atomic force microscopy and Raman microspectroscopy. A range of topographical and
      compositional changes on the surface of the retrievals are reported in this work.
      The study revealed that changes in roughness are the result of a combination of
      factors, i.e. scratching, surface upheaval due to transformation to the
      monoclinic phase and grain pull-out. Clusters of transformed monoclinic grains
      were observed on heads implanted for more than 3 years. The phase composition of
      these clusters was confirmed by Raman microspectroscopy. Increased abrasive wear
      and a higher monoclinic phase content concentrated on the pole of the femoral
      heads, confirming that the tetragonal to monoclinic phase transformation was not
      only induced by the tetragonal phase metastability and environmental conditions
      but mechanical and tribological factors, also affected the transformation
      kinetics. Additionally, the head implanted for 13 years showed evidence of a self
      polishing mechanism leading to a considerable smoothening of the surface. These
      observations provide an insight into the interrelated mechanisms underlying the
      wear and transformation process on zirconia ceramics during implantation. 

PMID- 24140385
TI  - Human urinary phthalate metabolites level and main semen parameters, sperm
      chromatin structure, sperm aneuploidy and reproductive hormones.
AB  - The aim of the study was to assess the association of phthalate metabolites
      levels in urine with semen parameters (sperm concentration, motility, morphology,
      CASA parameters), sperm chromatin structure, sperm aneuploidy and reproductive
      hormones. The study population consisted of 269 men who were attending an
      infertility clinic and had normal semen concentration (20-300mln/ml) or slight
      oligozoospermia (15-20mln/ml). Participants were interviewed and provided a semen
      sample. The phthalate metabolites were analysed in the urine using a procedure
      based on the LC-MS/MS method. Urinary phthalate metabolites levels were
      significantly associated with a decrease in sperm motility (5OH MEHP, MEHP,
      MINP), CASA parameters (MBP), testosterone level (MEHP) and an increase sperm DNA
      damage (MBP) and sperm aneuploidy (MBzP, MBP, MEHP, MEP). In view of the
      importance of human reproductive health and the widespread usage of phthalates,
      it is important to further investigate these correlations. 

PMID- 24140386
TI  - Repair and removal of azoxymethane-induced O6-methylguanine in rat colon by O6
      methylguanine DNA methyltransferase and apoptosis.
AB  - Azoxymethane (AOM) is an alkylating agent that generates mutagenic and
      carcinogenic O(6)-methylguanine (O(6)meG) adducts in DNA. O(6)meG has been
      detected in human colonic DNA; hence, understanding the innate cellular events
      occurring in response to the formation of O(6)meG is important in developing
      preventive strategies for colorectal cancer. We explored the time-course, dose
      response, and kinetics of O(6)meG formation and its removal by the DNA repair
      protein, O(6)-methylguanine DNA methyltransferase (MGMT), and apoptosis. In rats
      given AOM (10 mg/kg), the formation of O(6)meG occurs within 2 h of exposure,
      accompanied by rapid depletion of MGMT activity and followed by the induction of
      an acute apoptotic response that peaks at 6-8 h. MGMT repair and apoptosis are
      dependent on AOM dose and O(6)meG load. Apoptosis is initiated only when a high
      O(6)meG load is present and MGMT activity is fully depleted. AOM, 10 mg/kg,
      overwhelms MGMT repair for about 96 h and renewed MGMT activity is only observed
      once O(6)meG is no longer detectable. A threshold for apoptosis is observed at 6
      h after 6 mg/kg AOM, when a high O(6)meG persists and MGMT activity is very low.
      These data suggest that apoptosis is probably triggered by O(6)meG, but only once
      the capacity of MGMT to repair O(6)meG is exhausted. In the colonic epithelium,
      apoptosis may be complementary to MGMT, in terms of minimising potentially
      mutagenic events and maintaining a healthy genome.

PMID- 24140387
TI  - A translational assessment of preclinical versus clinical tools for the
      measurement of cardiac contractility: comparison of LV dP/dt(max) with
      echocardiography in telemetry implanted beagle dogs.
AB  - INTRODUCTION: Regarding evaluation of drug-induced changes in left ventricular
      contractility in safety pharmacology there is still a gap in knowledge between
      preclinically and clinically used measurements. METHODS: As a step towards
      translation of preclinical to clinical outcomes, this study in telemetered dogs
      was initiated to compare indexes of contractility, such as LV dP/dt(max)
      (contractility measured as the maximum raise of pressure in the left ventricle)
      and LV dP/dt(max)/P (contractility measured as the maximum raise of pressure in
      the left ventricle, corrected for pressure) (telemetry; both commonly
      preclinically used) and EF (ejection fraction) and FS (fractional shortening)
      (echocardiography; both commonly clinically used). Different inotropic states
      were induced by minoxidil, milrinone, isoprenaline, clonidine, atenolol and
      verapamil. RESULTS: Both techniques demonstrated reproducible changes in
      contractility which showed a clear linear association. A change in LV dP/dt(max)
      of 1000 mmHg/s (in the range of 2500 to 7500 mmHg/s; in healthy dogs)
      corresponded with a change in ejection fraction of approximately 7% and a
      fractional shortening of approximately 6%. A change of 10/s LV dP/dt(max)/P (in
      the range of 35 to 85/s; in healthy dogs) corresponded with a change in ejection
      fraction of approximately 7% and a fractional shortening of 7%. DISCUSSION: The
      correlation found in this study could potentially enable a better--translational-
      assessment of the clinical relevance of changes in contractility indices measured
      with telemetry devices in preclinical safety studies.

PMID- 24140388
TI  - Pharmacokinetic-pharmacodynamic modeling of QRS-prolongation by flecainide: heart
      rate-dependent effects during sinus rhythm in conscious telemetered dogs.
AB  - INTRODUCTION: The duration of the QRS interval is determined by the ion currents
      involved in cardiac depolarization. Class I antiarrhythmic drugs reduce cardiac
      excitability and conduction by inhibiting Nav1.5 channels responsible for I(Na),
      thus increasing the QRS interval. Previous studies in humans as well as in animal
      models have demonstrated a more pronounced effect on QRS-prolongation during
      higher heart rates. In the present study, the effects of the Nav1.5 inhibitor
      flecainide on cardiovascular parameters, were studied in the telemetered beagle
      dog under normal autonomic control. The heart rate dependency of QRS prolongation
      was characterized using pharmacokinetic-pharmacodynamic (PKPD) modeling. METHODS:
      Four male telemetered beagle dogs were administered placebo or flecainide (100,
      150 and 200 mg) in a Latin square design. The QRS interval and heart rate were
      recorded, and blood samples were taken. Plasma concentrations of flecainide were
      fitted to a one compartment oral model and the intrapolated plasma concentrations
      were fitted to QRS and heart rate data sampled during 5 h after dosing. RESULTS:
      Flecainide increased the QRS interval in all dogs, whereas there were no effects
      on heart rate. Using the PKPD model, a statistically significant heart rate
      dependent QRS prolongation was linked to individual concentration-time profiles
      of flecainide. DISCUSSION: PKPD analysis of QRS interval data from unrestrained
      dogs with sinus rhythm can elucidate mechanisms previously only described during
      controlled heart rhythm. Specific questions can therefore be addressed in
      generically designed cardiovascular telemetry safety studies and different types
      of relationships between parameters can be uncovered. In addition, the present
      approach can be used to better characterize drug-induced QRS effects in
      cardiovascular dog models.

PMID- 24140389
TI  - A multi-endpoint in vivo larval zebrafish (Danio rerio) model for the assessment
      of integrated cardiovascular function.
AB  - INTRODUCTION: Despite effective in vitro preclinical strategies to identify
      cardiovascular (CV) liabilities, there remains a need for early functional
      assessment prior to complex in vivo mammalian models. The larval zebrafish (Danio
      rerio, Zf) has been suggested for this role: previous data suggest that cardiac
      electrophysiology and vascular ultrastructure are comparable with mammals, and
      also indicate responsiveness of individual Zf CV system endpoints to some
      functional modulators. Little information is, however, available regarding
      integrated functional CV responses to drug treatment. Consequently, we developed
      a novel larval Zf model capable of simultaneous quantification of chronotropic,
      inotropic and arrhythmic effects, alongside measures of blood flow and vessel
      diameter. METHODS: Non-invasive video analysis of the heart and dorsal aorta of
      anaesthetized and agarose-embedded larval ZF was used to measure multiple
      cardiovascular endpoints, simultaneously, following treatment with a range of
      functional modulators of CV physiology. RESULTS: Changes in atrial and
      ventricular beat frequencies were detected in response to acute treatment with
      cardio-stimulants (adrenaline and theophylline), and negative chrono/inotropes
      (cisapride, haloperidol, terfenadine and verapamil). Arrhythmias were also
      observed including terfenadine-induced 2:1 atrial-ventricular (A-V) block, a
      previously proposed hERG surrogate measure. Significant increases in blood flow
      were detected in response to adrenaline and theophylline exposure; and decreases
      after cisapride, haloperidol, terfenadine, and verapamil treatment. Using dorsal
      aorta (DA) blood flow and ventricular beat rate, surrogate stoke volumes were
      also calculated for all compounds. DISCUSSION: These data support the use of this
      approach for CV function studies. Moreover the throughput and compound
      requirements (approximately 3 compounds/person effort/week and <10 mg) make our
      approach potentially suitable for higher throughput drug safety and efficacy
      applications, pending further assessment of ZF-mammalian pharmacological
      comparability.

PMID- 24140390
TI  - 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata,
      India: a cluster-randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Efficacy and safety of a two-dose regimen of bivalent killed whole
      cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is
      established, but long-term efficacy is not. We aimed to assess protective
      efficacy up to 5 years in a slum area of Kolkata, India. METHODS: In our double
      blind, cluster-randomised, placebo-controlled trial, we assessed incidence of
      cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings
      (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to
      receive two oral doses of modified killed bivalent whole-cell cholera vaccine or
      heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done
      by use of a computer-generated sequence in blocks of four. The primary endpoint
      was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea
      severe enough for patients to seek treatment in a health-care facility. We
      identified culture-confirmed cholera cases among participants seeking treatment
      for diarrhoea at a study clinic or government hospital between 14 days and 1825
      days after receipt of the second dose. We assessed vaccine protection in a per
      protocol population of participants who had completely ingested two doses of
      assigned study treatment. FINDINGS: 69 of 31 932 recipients of vaccine and 219 of
      34 968 recipients of placebo developed cholera during 5 year follow-up (incidence
      2.2 per 1000 in the vaccine group and 6.3 per 1000 in the placebo group).
      Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74;
      p<0.0001), and point estimates by year of follow-up suggested no evidence of
      decline in protective efficacy. INTERPRETATION: Sustained protection for 5 years
      at the level we reported has not been noted previously with other oral cholera
      vaccines. Established long-term efficacy of this vaccine could assist policy
      makers formulate rational vaccination strategies to reduce overall cholera burden
      in endemic settings. FUNDING: Bill & Melinda Gates Foundation and the governments
      of South Korea and Sweden.

PMID- 24140391
TI  - A rare success for cholera vaccines.

PMID- 24140392
TI  - Mutation of a pH-modulating residue in a GH51 alpha-l-arabinofuranosidase leads
      to a severe reduction of the secondary hydrolysis of transfuranosylation
      products.
AB  - BACKGROUND: The development of enzyme-mediated glycosynthesis using glycoside
      hydrolases is still an inexact science, because the underlying molecular
      determinants of transglycosylation are not well understood. In the framework of
      this challenge, this study focused on the family GH51 alpha-l-arabinofuranosidase
      from Thermobacillus xylanilyticus, with the aim to understand why the mutation of
      position 344 provokes a significant modification of the
      transglycosylation/hydrolysis partition. METHODS: Detailed kinetic analysis
      (kcat, KM, pKa determination and time-course NMR kinetics) and saturation
      transfer difference nuclear magnetic resonance spectroscopy was employed to
      determine the synthetic and hydrolytic ability modification induced by the
      redundant N344 mutation disclosed in libraries from directed evolution. RESULTS:
      The mutants N344P and N344Y displayed crippled hydrolytic abilities, and thus
      procured improved transglycosylation yields. This behavior was correlated with an
      increased pKa of the catalytic nucleophile (E298), the pKa of the acid/base
      catalyst remaining unaffected. Finally, mutations at position 344 provoked a pH
      dependent product inhibition phenomenon, which is likely to be the result of a
      significant modification of the proton sharing network in the mutants.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: Using a combination of biochemical and
      biophysical methods, we have studied TxAbf-N344 mutants, thus revealing some
      fundamental details concerning pH modulation. Although these results concern a
      GH51 alpha-l-arabinofuranosidase, it is likely that the general lessons that can
      be drawn from them will be applicable to other glycoside hydrolases. Moreover,
      the effects of mutations at position 344 on the transglycosylation/hydrolysis
      partition provide clues as to how TxAbf can be further engineered to obtain an
      efficient transfuranosidase.

PMID- 24140393
TI  - Parasite aquaporins: current developments in drug facilitation and resistance.
AB  - BACKGROUND: Although being situated in a niche, research on parasite aquaporins
      is a lively field that has provided new insight into basic aquaporin structure
      function relationships and physiological roles of water and solute transport.
      Moreover, it bears the potential to find novel approaches to antiparasitic
      chemotherapy. SCOPE OF REVIEW: Here, we summarize the current knowledge about the
      structure and substrate selectivity of aquaporins from protozoan and helminth
      parasites, review the current views on their physiological roles, and discuss
      their potency for chemotherapy. MAJOR CONCLUSIONS: Parasite aquaporins fulfill
      highly diverse tasks in the physiology of the various organisms, yet their
      general protein structure is well conserved. Aquaporins are directly
      (antimonials) and indirectly (melarsoprol, pentamidine) linked to the uptake of
      antiparasitic drugs. Unfortunately, drug-like aquaporin inhibitors are still
      missing. GENERAL SIGNIFICANCE: Aquaporins expression levels determine the degree
      of parasite resistance against certain drugs. Further studies on parasite
      aquaporins may provide data about overcoming drug resistance mechanisms or even
      spark novel treatments. This article is part of a Special Issue entitled
      Aquaporins.

PMID- 24140394
TI  - Physico-chemical characterization and the in vitro genotoxicity of medical
      implants metal alloy (TiAlV and CoCrMo) and polyethylene particles in human
      lymphocytes.
AB  - BACKGROUND: The main objective of the present study was to investigate chemical
      composition and possible cyto/genotoxic potential of several medical implant
      materials commonly used in total hip joint replacement. METHODS: Medical implant
      metal alloy (Ti6Al4V and CoCrMo) and high density polyethylene particles were
      analyzed by energy dispersive X-ray spectrometry while toxicological
      characterization was done on human lymphocytes using multi-biomarker approach.
      RESULTS: Energy dispersive X-ray spectrometry showed that none of the elements
      identified deviate from the chemical composition defined by appropriate ISO
      standard. Toxicological characterization showed that the tested materials were
      non-cyto/genotoxic as determined by the comet and cytokinesis-block micronucleus
      (CBMN) assay. Particle morphology was found (by using scanning electron and
      optical microscope) as flat, sharp-edged, irregularly shaped fiber-like grains
      with the mean particle size less than 10um; this corresponds to the so-called
      "submicron wear". The very large surface area per wear volume enables high
      reactivity with surrounding media and cellular elements. CONCLUSIONS: Although
      orthopedic implants proved to be non-cyto/genotoxic, in tested concentration
      (10MUg/ml) there is a constant need for monitoring of patients that have
      implanted artificial hips or other joints, to minimize the risks of any unwanted
      health effects. GENERAL SIGNIFICANCE: The fractal and multifractal analyses,
      performed in order to evaluate the degree of particle shape effect, showed that
      the fractal and multifractal terms are related to the "remnant" level of the
      particles' toxicity especially with the cell viability (trypan blue method) and
      total number of nucleoplasmic bridges and nuclear buds as CBMN assay parameters.

PMID- 24140395
TI  - AAC intervention using a VOCA for deaf children with multiple disabilities who
      received cochlear implantation.
AB  - OBJECTIVES: The aim of this study was to examine the efficacy of a new
      habilitation approach, augmentative and alternative communication (AAC)
      intervention using a voice output communication aid (VOCA), in improving speech
      perception, speech production, receptive vocabulary skills, and communicative
      behaviors in children with cochlear implants (CIs) who had multiple disabilities.
      METHODS: Five children with mental retardation and/or cerebral palsy who had used
      CIs over two years were included in this study. Five children in the control
      group were matched to children who had AAC intervention on the basis of the
      type/severity of their additional disabilities and chronological age. They had
      limited oral communication skills after cochlear implantation because of their
      limited cognition and oromotor function. The children attended the AAC
      intervention with parents once a week for 6 months. We evaluated their
      performance using formal tests, including the monosyllabic word tests, the
      articulation test, and the receptive vocabulary test. We also assessed parent
      child interactions. We analyzed the data using a one-group pretest and posttest
      design. RESULTS: The mean scores of the formal tests performed in these children
      improved from 26% to 48% in the phoneme scores of the monosyllabic word tests,
      from 17% to 35% in the articulation test, and from 11 to 18.4 in the receptive
      vocabulary test after AAC intervention (all p < .05). Some children in the
      control group showed improvement in the speech perception, speech production, and
      receptive vocabulary tests for 6 months, but the differences did not achieve
      statistical significance (all p > .05). The frequency of spontaneous
      communicative behaviors (i.e., vocalization, gestures, and words) and imitative
      words significantly increased after AAC intervention (p < .05). CONCLUSIONS: AAC
      intervention using a VOCA was very useful and effective on improving
      communicative skills in children with multiple disabilities who had very limited
      oral communication skills after cochlear implantation.

PMID- 24140397
TI  - Molecular Genetics and Metabolism.

PMID- 24140398
TI  - Detection of a novel intragenic rearrangement in the creatine transporter gene by
      next generation sequencing.
AB  - Deficiency caused by mutations in the creatine transporter gene (SLC6A8/CT1) is
      an X-linked form of intellectual disability. The presence of highly homologous
      pseudogenes and high GC content of SLC6A8 genomic sequence complicates the
      molecular diagnosis of this disorder. To minimize the pseudogene interference,
      exons 2 to 13 of SLC6A8 were amplified as a single PCR product using gene
      specific long-range PCR (LR-PCR) primers. The GC-rich exon 1 and its flanking
      intronic sequences were amplified separately in a short fragment under GC-rich
      conditions and a touchdown PCR program. Traditional Sanger sequence analysis of
      all coding exons of SLC6A8 from a 3-year-old boy with creatine transporter
      deficiency did not detect deleterious mutations. The long-range PCR product was
      used as template followed by massively parallel sequencing (MPS) on HiSeq2000. We
      were able to detect a tandem duplication involving part of exons 11 and 12 in the
      SLC6A8 gene. The deduced c.1592_1639dup133 mutation was confirmed to be a
      hemizygous insertion by targeted genomic DNA and cDNA Sanger sequencing.
      Combination of deep sequencing technology with long-range PCR revealed a novel
      intragenic duplication in the SLC6A8 gene, providing a definitive molecular
      diagnosis of creatine transporter deficiency in a male patient. 

PMID- 24140396
TI  - Pathogenesis, diagnosis, and management of cholangiocarcinoma.
AB  - Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of
      cholangiocyte differentiation; they can be classified anatomically as
      intrahepatic CCA (iCCA), perihilar CCA (pCCA), or distal CCA. These subtypes
      differ not only in their anatomic location, but in epidemiology, origin,
      etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has
      been increasing over the past 3 decades, and only a low percentage of patients
      survive until 5 years after diagnosis. Geographic variations in the incidence of
      CCA are related to variations in risk factors. Changes in oncogene and
      inflammatory signaling pathways, as well as genetic and epigenetic alterations
      and chromosome aberrations, have been shown to contribute to the development of
      CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer
      associated fibroblasts, which promotes their progression. We have gained a better
      understanding of the imaging characteristics of iCCAs and have developed advanced
      cytologic techniques to detect pCCAs. Patients with iCCAs usually are treated
      surgically, whereas liver transplantation after neoadjuvant chemoradiation is an
      option for a subset of patients with pCCAs. We review recent developments in our
      understanding of the epidemiology and pathogenesis of CCA, along with advances in
      classification, diagnosis, and treatment. 

PMID- 24140400
TI  - Degradation of conazole fungicides in water by electrochemical oxidation.
AB  - The electrochemical oxidation (EO) treatment in water of three conazole
      fungicides, myclobutanil, triadimefon and propiconazole, has been carried out at
      constant current using a BDD/SS system. First, solutions of each fungicide were
      electrolyzed to assess the effect of the experimental parameters such as current,
      pH and fungicide concentration on the decay of each compound and total organic
      carbon abatement. Then a careful analysis of the degradation by-products was made
      by high performance liquid chromatography, ion chromatography and gas
      chromatography coupled with mass spectrometry in order to provide a detailed
      discussion on the original reaction pathways. Thus, during the degradation of
      conazole fungicides by the electrochemical oxidation process, aromatic
      intermediates, aliphatic carboxylic acids and Cl(-) were detected prior to their
      complete mineralization to CO2 while NO3(-) anions remained in the treated
      solution. This is an essential preliminary step towards the applicability of the
      EO processes for the treatment of wastewater containing conazole fungicides. 

PMID- 24140401
TI  - Psychoactive substances--some new, some old: a scan of the situation in the U.S.
AB  - INTRODUCTION: New synthetic drugs are appearing as old hallucinogen psychedelic
      drugs are reappearing. This article combines the findings from a variety of
      datasets to characterize the users in terms of gender, age, drug use patterns,
      and adverse results, as well as provide an overview of the changes in
      formulations of these drugs and the impact of legal controls. Methods. Data from
      Monitoring the Future and the National Survey on Drug Use and Health are
      analyzed, along with the national DAWN emergency room admissions, Texas poison
      control center cases, and Texas treatment data, along with national forensic
      laboratory results. Results. Users of the synthetic cannabinoids, synthetic
      cathinones, phenethylamines, tryptamines, LSD, MDMA, and mushrooms tended to be
      young and male. They differed in terms of race and ethnicity. The effects of the
      drugs differed in terms of emergency room outcomes and poison center reports, and
      the treatment data showed they were similar in terms of education level,
      employment, and legal problems. Conclusion. Combining the different data sources
      provided a first picture of the characteristics of these users and their needs.
      Creditable descriptions on the risks of these drugs should be disseminated.
      Intervention programs should be targeted to these young users and new
      neuropsychobiological deficits from some of these drugs should be monitored.
      Because of the ever-changing chemical combinations to stay legal and the need for
      information on content and dosage, a more effective approach may be needed basing
      control on the effects of the substances rather than their changing chemical
      composition.

PMID- 24140399
TI  - Common and distinct neural targets of treatment: changing brain function in
      substance addiction.
AB  - Neuroimaging offers an opportunity to examine the neurobiological effects of
      therapeutic interventions for human drug addiction. Using activation likelihood
      estimation, the aim of the current meta-analysis was to quantitatively summarize
      functional neuroimaging studies of pharmacological and cognitive-based
      interventions for drug addiction, with an emphasis on their common and distinct
      neural targets. More exploratory analyses also contrasted subgroups of studies
      based on specific study and sample characteristics. The ventral striatum, a
      region implicated in reward, motivation, and craving, and the inferior frontal
      gyrus and orbitofrontal cortex, regions involved in inhibitory control and goal
      directed behavior, were identified as common targets of pharmacological and
      cognitive-based interventions; these regions were observed when the analysis was
      limited to only studies that used established or efficacious interventions, and
      across imaging paradigms and types of addictions. Consistent with theoretical
      models, cognitive-based interventions were additionally more likely to activate
      the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in
      self-referential processing, cognitive control, and attention. These results
      suggest that therapeutic interventions for addiction may target the brain
      structures that are altered across addictions and identify potential
      neurobiological mechanisms by which the tandem use of pharmacological and
      cognitive-based interventions may yield synergistic or complementary effects.
      These findings could inform the selection of novel functional targets in future
      treatment development for this difficult-to-treat disorder. 

PMID- 24140402
TI  - An amperometric hypoxanthine biosensor based on Au@FeNPs for determination of
      hypoxanthine in meat samples.
AB  - A xanthine oxidase (XOD) from buttermilk was immobilized covalently onto boronic
      acid functionalized gold coated iron nanoparticles (Au@FeNPs) electrodeposited on
      pencil graphite (PG) electrode, via the boroester linkages, between free hydroxyl
      groups of boronic acid, alpha-COOH and -NH2 groups of enzyme. The surface
      functionalization of Fe/Au nanoparticles with boronic acid (Au@FeNPs) on pencil
      graphite (PG) electrode was characterized by Fourier transform infrared (FTIR),
      cyclic voltammetry (CV), scanning electron microscopy (SEM), atomic force
      microscopy (AFM) and Electrochemical impedance spectroscopy (EIS) before and
      after immobilization of XOD. The biosensor exhibited optimum response within 3s
      at pH 7.2 and 30  degrees C and linearity in the range, 0.05 MUM to 150 MUM for
      hypoxanthine with a detection limit of 0.05 MUM (S/N=3). Apparent Michaelis
      Menten constant (Km(app)) for hypoxanthine was 40 MUM and Imax 0.125 mA. The
      biosensor was employed to determine hypoxanthine in fish, chicken, pork, beef
      meat and lost 50% of its initial activity after its 200 uses over 100 days, when
      stored at 4  degrees C.

PMID- 24140403
TI  - Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in
      Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of
      fasting.
AB  - Melanin-concentrating hormone (MCH) is classically known for its role in
      regulating teleost fish skin color change for environmental adaptation. Recent
      evidence suggests that MCH also has appetite-stimulating properties. The
      gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine
      control of reproduction and energy status in fish. Atlantic cod (Gadus morhua)
      are a commercially important aquaculture species inhabiting the shores of
      Atlantic Canada. In this study, we examine MCH and GnRH transcript expression
      profiles during early development as well as in central and peripheral tissues
      and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions
      following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod
      eggs, while MCH has variable expression throughout early development. GnRH2 and
      GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed.
      For both MCH and GnRH, highest expression appears during the exogenous feeding
      stages, perhaps supporting their functions as appetite regulators during early
      development. MCH and GnRH transcripts are found in brain regions related to
      appetite regulation (telencephalon/preoptic area, optic tectum/thalamus,
      hypothalamus), as well as the pituitary gland and the stomach, suggesting a
      peripheral function in food intake regulation. Atlantic cod MCH mRNA is
      upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be
      influenced by food deprivation. In conclusion, MCH might be involved in
      stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more
      significant role in appetite regulation during early development. 

PMID- 24140404
TI  - Development of a seaweed derived platelet activating factor acetylhydrolase (PAF
      AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of
      their toxicity using the Zebrafish larvae assay.
AB  - The vascular inflammatory role of platelet activating factor acetylhydrolase (PAF
      AH) is thought to be due to the formation of lysophosphatidyl choline and
      oxidized non-esterified fatty acids. This enzyme is considered a promising
      therapeutic target for the prevention of atherosclerosis and there is a need to
      expand the available chemical templates of PAF-AH inhibitors. This study
      demonstrated how natural PAF-AH inhibitory peptides were isolated and
      characterized from the red macroalga Palmaria palmata. The dried powdered alga
      was hydrolyzed using the food grade enzyme papain, and the resultant peptide
      containing fraction generated using RP-HPLC. Several oligopeptides were
      identified as potential PAF-AH inhibitors following bio-guided fractionation, and
      the amino acid sequences of these oligopeptides were confirmed by Q-TOF-MS and
      microwave-assisted solid phase de novo synthesis. The most promising PAF-AH
      inhibitory peptide had the amino acid sequence NIGK and a PAF-AH IC50 value of
      2.32 mM. This peptide may constitute a valid drug template for PAF-AH inhibitors.
      Furthermore the P. palmata hydrolysate was nontoxic when assayed using the
      Zebrafish toxicity model at a concentration of 1mg/ml.

PMID- 24140405
TI  - Value of proBNP1-108 testing for the risk stratification of patients with
      systolic heart failure.
AB  - The study objectives were to determine the circulating levels of proBNP1-108, the
      precursor of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT
      proBNP), in patients with systolic heart failure (HF) and to assess their
      prognosis value for cardiovascular (CV) death over a long-term follow-up. Seventy
      three patients with systolic HF and 68 healthy volunteers were included. ProBNP1
      108, BNP and NT-proBNP levels were measured with automated immunoassays and their
      predictive value for long-term survival was assessed through an 8 years follow
      up. ProBNP1-108 levels were markedly increased in patients with systolic HF in
      comparison to healthy volunteers. In univariate proportional hazard model,
      survival was related to proBNP1-108, BNP, NT-proBNP, age, EF and glomerular
      filtration rate (eGFR). Kaplan-Meier survival curves according to proBNP tertiles
      diverged significantly, and the highest proBNP levels were related to patients
      with the highest risk of CV death. In a multivariate analysis including age, EF,
      proBNP1-108, BNP, NT-proBNP, and eGFR levels, NT-proBNP was the strongest
      predictor of long term CV death. Our study therefore demonstrated that high
      levels of proBNP1-108, measured with an assay with enhanced analytical
      specificity, are related to the long-term risk of cardiovascular death in
      systolic heart failure. 

PMID- 24140406
TI  - Gender difference in tumor necrosis factor-alpha production in human neutrophils
      stimulated by lipopolysaccharide and interferon-gamma.
AB  - The gender difference in tumor necrosis factor-alpha (TNF-alpha) production in
      human neutrophils stimulated by lipopolysaccharide (LPS) and interferon-gamma
      (IFN-gamma) was explored by using peripheral blood neutrophils from young men and
      women. As compared with female neutrophils, male neutrophils released greater
      amounts of TNF-alpha, and exhibited stronger activation of mitogen-activated
      protein kinases and phosphatidylinositol 3-kinase in response to LPS stimulation.
      LPS-induced TNF-alpha production was markedly enhanced by pretreatment of cells
      with IFN-gamma, and IFN-gamma-mediated priming in male neutrophils was
      significantly greater than that in female neutrophils. Male neutrophils showed
      higher expression of TLR4, but not IFN-gamma receptors, than female neutrophils,
      and its expression was increased by stimulation with IFN-gamma or IFN-gamma plus
      LPS. These findings indicate that male neutrophils show higher responsiveness to
      stimulation with LPS and IFN-gamma than female neutrophils, and suggest that the
      gender difference in neutrophil responsiveness to LPS and IFN-gamma is partly
      responsible for that in the outcome of sepsis, in which premenopausal women show
      a favorable prognosis as compared with men. 

PMID- 24140407
TI  - Generation of robust vascular networks from cardiovascular blast populations
      derived from human induced pluripotent stem cells in vivo and ex vivo organ
      culture system.
AB  - Vascular network formation is a key therapeutic event in regenerative medicine
      because it is essential for mitigating or ameliorating ischemic conditions
      implicated in various diseases and repair of tissues and organs. In this study,
      we induced human induced pluripotent stem cells (hiPSCs) to differentiate into
      heterogeneous cell populations which have abilities to form vascular vessel-like
      structures by recapitulating the embryonic process of vasculogenesis in vitro.
      These cell populations, named cardiovascular blast populations (CBPs) in this
      report, primarily consisted of CD31(+) and CD90(+) cells. By using cell-sheet
      technology, we observed that CBP with CD31(+) cells to CD90(+) cells in the ratio
      of 1:1.5 could reproducibly form robust vascular networks in vivo and ex vivo
      organ culture system. To our knowledge, this is the first report demonstrating
      the generation of vascular network from hiPSCs in ex vivo organ culture system
      that correlates closely with in vivo results. Our results suggest that CBP
      provides a promising approach for studying vasculogenesis and subsequently can be
      used in regenerative medicine. 

PMID- 24140408
TI  - Neuregulin 1-beta regulates cell adhesion molecule L1 expression in the cortex
      and hippocampus of mice.
AB  - Neuregulin 1 (Nrg1) functions in neuronal migration, survival and differentiation
      as well as synaptogenesis during ontogenetic development and maintenance of
      synaptic functions in the adult mammalian brain. The neural adhesion molecule L1
      (L1CAM) functions in similar overlapping, but also non-overlapping roles in the
      nervous system. In the present study, we therefore investigated some aspects of
      the functional relationship between Nrg1 and L1 in mammalian neural cells. Nrg1
      regulates the expression of L1 in cultures of both human neuroblastoma SK-N-SH
      cells and mouse cortical and hippocampal neurons. To analyze the role of Nrg1 on
      L1 expression in vivo, young adult male mice received intraperitoneal injections
      of Nrg1 or PBS (vehicle control). The correlation between Nrg1 and L1 expression
      was tested by qPCR, Western blot analysis, and immunocytology. Our data indicate
      that neuregulin 1-beta (Nrg1beta) increases L1 expression in neurons of the
      cerebral cortex, and decreases expression in neurons of the hippocampus in vitro
      and in vivo. In addition, Nrg1 induces phosphorylation of its receptors, ErbB2
      and ErbB4, the predominant ErbB receptors in the nervous system. These results
      show that Nrg1beta affects expression of L1 in the central nervous system and in
      parallel activates the ErbB receptors for Nrg1, suggesting a crosstalk between
      molecules that are of prime importance for nervous system functions. 

PMID- 24140409
TI  - Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR
      gamma/LXR-alpha signaling pathway.
AB  - Cholesterol efflux from macrophages is a critical mechanism to prevent the
      development of atherosclerosis. Here, we sought to investigate the effects of
      arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in
      oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data
      showed that arctigenin significantly accelerated apolipoprotein A-I- and high
      density lipoprotein-induced cholesterol efflux in both dose- and time-dependent
      manners. Moreover, arctigenin treatment enhanced the expression of ATP binding
      cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules
      in the initial step of cholesterol efflux, at both mRNA and protein levels.
      Arctigenin also caused a concentration-dependent elevation in the expression of
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and liver X
      receptor-alpha (LXR-alpha). The arctigenin-mediated induction of ABCA1, ABCG1,
      and apoE was abolished by specific inhibition of PPAR-gamma or LXR-alpha using
      small interfering RNA technology. Our results collectively indicate that
      arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through
      upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced
      expression of PPAR-gamma and LXR-alpha.

PMID- 24140410
TI  - Effect of oral imperatorin on memory in mice.
AB  - The aim of this study was to explore the effect of the acetylcholinesterase
      inhibiting mixture of extracts of Angelica archangelica fruit and Geranium
      sylvaticum on memory. Furthermore the effect of the main compound, the
      furanocoumarin imperatorin, which has been shown to affect several
      neurotransmitters, was studied. Passive avoidance was measured by step-down
      latency and step-through latency of 10 months old mice receiving 0.79 mg/kg of
      imperatorin daily, pure or as part of the extracts, for 14 days or longer. Step
      down latency was significantly higher in both groups receiving imperatorin than
      in the control group. In contrast, no difference was found between treatment
      groups regarding step-through latency. The results indicate that the imperatorin
      is the main active component of the extract mixture.

PMID- 24140411
TI  - Cucurbitacin D is a new inflammasome activator in macrophages.
AB  - We previously reported that cucurbitacin D isolated from Trichosanthes kirilowii
      has anti-tumor roles to leukemia cells. However, the effect of cucurbitacin D on
      immune cells is not fully understood although there is no toxic activity to
      normal cells. In this study, immunomodulating activities of cucurbitacin D were
      investigated in macrophages. Cucurbitacin D could increase LPS-induced
      interleukin (IL)-1beta production in culture supernatant of THP-1 cells,
      peritoneal exudate cells (PECs), bone marrow derived macrophages (BMDMs), and
      RAW264 cells. At the transcriptional level, cucurbitacin D enhanced LPS-induced
      IL-1beta mRNA expression through activation of ERK1/2 mitogen-activated protein
      kinases (MAPKs). At the posttranscriptional level, the activation of caspase-1
      induced by cucurbitacin D has also been demonstrated following treatment with a
      caspase-1 inhibitor and siRNA. Importantly, cucurbitacin D has further been shown
      to induce inflammasome activation independent of ERK1/2 activation. Western
      blotting showed interaction of NOD-like receptor family, pyrin domain containing
      3 (NALP3) and apoptosis-associated speck-like protein containing a caspase
      activating and recruitment domain (ASC), suggesting activation of the
      inflammasome and a possible reason for activation of caspase-1. Taken together,
      these results suggest that cucurbitacin D could initiate immunomodulating
      activity in macrophages to lead to inflammasome activation as well as enhancement
      of LPS signaling. 

PMID- 24140412
TI  - Distribution of dopaminergic cell bodies in the median raphe nucleus of the rat
      brain.
AB  - An increasing amount of data suggests that a dysfunction in dopamine (DA)
      neurotransmission is involved in the pathophysiology of various neurological and
      psychiatric disorders. With this in mind, the distribution and connectivity of
      the dopaminergic system in the rat brain has been studied extensively. So far,
      little is known about the distribution of DA containing neurons in the median
      raphe nucleus (MnR). This nucleus is mainly defined by a large population of
      serotonin containing neurons. Using quantitative immunohistochemistry, we
      observed the presence of a small number of DA containing neurons in the rat MnR,
      which was in contrast to a previous report. 

PMID- 24140414
TI  - Sodium-hydrogen exchangers (NHE) in human cardiovascular diseases: interfering
      strategies and their therapeutic applications.
AB  - Sodium-hydrogen exchangers (NHE) are among the main regulators of cell volume and
      intracellular concentration of hydrogen and sodium ions. By indirectly affecting
      sodium/calcium exchange across the plasma membrane, NHE can also influence the
      intracellular concentration of calcium. Excess activation of NHE or inappropriate
      sodium extrusion due to failure of ATP-dependent Na(+)/K(+) transport system can
      be deleterious during cardiac or peripheral organ ischemia. Besides being
      responsible for the regulation of intracellular pH and sodium-calcium inward
      currents, NHE isoform 1 (NHE-1), which is predominantly expressed in the
      cardiovascular system, influences the tone of the vessel wall in response to a
      variety of stimuli, including hypertonic stress. Because of the extensive
      involvement of NHE-1 in cardiac myocyte contracture and necrosis, stunning,
      reperfusion arrhythmias, as well as hypertension and myocardial diseases such as
      diabetic cardiomyopathy, efforts have been made in developing inhibitors of this
      transporter. We here review the biology and regulation of NHE, focusing on
      current knowledge of the role of NHE-1 as a potential target in the development
      of novel compounds that could play a role in cardiovascular homeostasis, both in
      physiological and pathological conditions. 

PMID- 24140413
TI  - Mitochondrial DNA mutations and breast tumorigenesis.
AB  - Breast cancer is a heterogeneous disease and genetic factors play an important
      role in its genesis. Although mutations in tumor suppressors and oncogenes
      encoded by the nuclear genome are known to play a critical role in breast
      tumorigenesis, the contribution of the mitochondrial genome to this process is
      unclear. Like the nuclear genome, the mitochondrial genome also encodes proteins
      critical for mitochondrion functions such as oxidative phosphorylation (OXPHOS),
      which is known to be defective in cancer including breast cancer. Mitochondrial
      DNA (mtDNA) is more susceptible to mutations due to limited repair mechanisms
      compared to nuclear DNA (nDNA). Thus changes in mitochondrial genes could also
      contribute to the development of breast cancer. In this review we discuss mtDNA
      mutations that affect OXPHOS. Continuous acquisition of mtDNA mutations and
      selection of advantageous mutations ultimately leads to generation of cells that
      propagate uncontrollably to form tumors. Since irreversible damage to OXPHOS
      leads to a shift in energy metabolism towards enhanced aerobic glycolysis in most
      cancers, mutations in mtDNA represent an early event during breast tumorigenesis,
      and thus may serve as potential biomarkers for early detection and prognosis of
      breast cancer. Because mtDNA mutations lead to defective OXPHOS, development of
      agents that target OXPHOS will provide specificity for preventative and
      therapeutic agents against breast cancer with minimal toxicity. 

PMID- 24140415
TI  - Upgrading dilute ethanol from syngas fermentation to n-caproate with reactor
      microbiomes.
AB  - Fermentation of syngas from renewable biomass, which is part of the syngas
      platform, is gaining momentum. Here, the objective was to evaluate a proof-of
      concept bioprocessing system with diluted ethanol and acetic acid in actual
      syngas fermentation effluent as the substrate for chain elongation into the
      product n-caproic acid, which can be separated with less energy input than
      ethanol. Chain elongation is performed with open cultures of microbial
      populations (reactor microbiomes) as part of the carboxylate platform. The
      highest concentration of n-caproic acid of ~1 g L(-1) was produced at a pH of
      5.44 and a production rate of 1.7 g L(-1) day(-1). A higher n-butyrate production
      rate of 20 g L(-1) day(-1) indicated that product toxicity was limiting the chain
      elongation step from n-butyric acid to n-caproic acid. This result shows that the
      syngas and carboxylate platforms can be integrated within a biorefinery, but that
      product separation is necessary.

PMID- 24140416
TI  - Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1.
AB  - BACKGROUND: In patients with myotonic dystrophy type 1 (DM1), the mechanisms
      underlying sudden cardiac death, which occurs in up to 1/3 of patients, are
      unclear. AIMS: To study the potential role of Brugada syndrome in ventricular
      tachyarrhythmias and sudden death in DM1 patients. METHODS: We screened 914 adult
      patients included in the DM1 Heart Registry during 2000-2009 for the presence of
      type 1 Brugada pattern on electrocardiogram (ECG). We also performed direct
      sequencing of SCN5A in patients with Brugada pattern. Further, we analysed SCN5A
      splicing on ventricular myocardial specimens harvested during cardiac
      transplantation in a 45-year-old patient with DM1 and three controls with
      inherited dilated cardiomyopathy. RESULTS: A type 1 Brugada pattern was present
      on the ECG of seven of 914 patients (0.8%), including five with a history of
      sustained ventricular tachyarrhythmia or sudden death, who fulfilled the criteria
      for Brugada syndrome. SCN5A sequencing was normal in all patients. Ventricular
      myocardial specimen analysis displayed abnormal splicing of SCN5A exon 6,
      characterized by over-expression of the 'neonatal' isoform, called exon 6A, in
      the patient with DM1, but not from the controls. CONCLUSION: Our findings suggest
      a potential implication of Brugada syndrome in sudden death in DM1, which may be
      related to missplicing of SCN5A. Our findings provide a new insight into the
      pathophysiology of heart disease in DM1.

PMID- 24140417
TI  - First hospitalization for heart failure in France in 2009: patient
      characteristics and 30-day follow-up.
AB  - BACKGROUND: The incidence of heart failure (HF) is stable in industrialized
      countries, but its prevalence continues to increase, especially due to the ageing
      of the population, and mortality remains high. OBJECTIVE: To estimate the
      incidence in France and describe the management and short-term outcome of
      patients hospitalized for HF for the first time. METHOD: The study population
      comprised French national health insurance general scheme beneficiaries (77% of
      the French population) hospitalized in 2009 with a principal diagnosis of HF
      after exclusion of those hospitalized for HF between 2006 and 2008 or with a
      chronic disease status for HF. Data were collected from the national health
      insurance information system (SNIIRAM). RESULTS: A total of 69,958 patients (mean
      age 78 years; 48% men) were included. The incidence of first hospitalization for
      HF was 0.14% (>= 55 years, 0.5%; >= 90 years, 3.1%). Compared with controls
      without HF, patients more frequently presented cardiovascular or other co
      morbidities. The hospital mortality rate was 6.4% and the mortality rate during
      the 30 days after discharge was 4.4% (3.4% without readmission). Among 30-day
      survivors, all-cause and HF 30-day readmission rates were 18% (< 70 years, 22%;
      >= 90 years, 13%) and 5%, respectively. Reimbursements among 30-day survivors
      comprised at least a beta-blocker in 54% of cases, diuretics in 85%, angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in
      67%, a diuretic and ACEI/ARB combination in 23% and a beta-blocker, ACEI/ARB and
      diuretic combination in 37%. CONCLUSION: Patients admitted for HF presented high
      rates of co-morbidity, readmission and death at 30 days, and there remains room
      for improvement in their drug treatments; these findings indicate the need for
      improvement in return-home and therapeutic education programmes.

PMID- 24140418
TI  - The effect of group size on vigilance in a semi-solitary, fossorial marsupial
      (Lasiorhinus latifrons).
AB  - Prey species that congregate gain protection against predatory attacks and this
      advantage is often reflected by a reduction in vigilance behaviour by individuals
      in larger groups. Comparatively few studies have investigated vigilance in
      solitary animals, but those that have, found that vigilance increases as group
      size increases because of the threat posed by conspecifics and/or competition for
      resources. The southern hairy-nosed wombat (Lasiorhinus latifrons) is a large
      fossorial, nocturnal marsupial that is neither strictly solitary nor gregarious,
      sharing warren systems with multiple conspecifics. We investigated the effects of
      conspecific presence on vigilance behaviour in this semi-solitary species. We
      observed wild-born, adult L. latifrons wombats in three group sizes (Large (1?,
      3?), Medium (1?, 2?) and Small (1?, 1?)) in a captive, naturalistic environment
      that allowed above-ground and den behaviour monitoring. Vigilance behaviours were
      performed less frequently by wombats in large groups (e.g. scanning, counts/day,
      Large: 55, Medium: 69, Small: 115, P=0.002) and more frequently as the distance
      from their nearest conspecific increased (r64=0.30, P= 0.016). Vigilance within
      burrows was also affected by social influences, with solitary wombats
      significantly more vigilant than those denning with a conspecific (e.g. scanning:
      conspecific absent: 0.13/5min, present: 0.03/5min, P<0.0001). It is concluded
      that the presence of conspecifics reduces vigilance in L. latifrons wombats, even
      within burrows, and this may partially explain the occurrence of warren sharing
      in the wild. 

PMID- 24140419
TI  - Analysis of the effects of stromal cells on the migration of lymphocytes into and
      through inflamed tissue using 3-D culture models.
AB  - Stromal cells may regulate the recruitment and behaviour of leukocytes during an
      inflammatory response, potentially through interaction with the endothelial cells
      (EC) and the leukocytes themselves. Here we describe new in vitro methodologies
      to characterise the effects of stromal cells on the migration of lymphocytes
      through endothelium and its underlying matrix. Three-dimensional tissue-like
      constructs were created in which EC were cultured above a stromal layer
      incorporating fibroblasts either as a monolayer on a porous filter or dispersed
      within a matrix of collagen type 1. A major advantage of these constructs is that
      they enable each step in leukocyte migration to be analysed in sequence
      (migration through EC and then stroma), as would occur in vivo. Migrated cells
      can also be retrieved from the constructs to identify which subsets traffic more
      effectively and how their functional responses evolve during migration. We found
      that culture of EC with dermal fibroblasts promoted lymphocyte transendothelial
      migration but not onward transit through matrix. A critical factor influencing
      the effect of fibroblasts on recruitment proved to be their proximity to the EC,
      with direct contact tending to disrupt migration. Comparison of the different
      approaches indicates that choice of an appropriate 3-D model enables the steps in
      lymphocyte entry into tissue to be studied in sequence, the regulatory mechanism
      to be dissected, and the effects of changes in stroma to be investigated. 

PMID- 24140420
TI  - Arginine methylation modulates autophagic degradation of PGL granules in C.
      elegans.
AB  - The selective degradation of intracellular components by autophagy involves
      sequential interactions of the cargo with a receptor, which also binds the
      autophagosomal protein Atg8 and a scaffold protein. Here, we demonstrated that
      mutations in C. elegans epg-11, which encodes an arginine methyltransferase
      homologous to PRMT1, cause the defective removal of PGL-1 and PGL-3 (cargo)-SEPA
      1 (receptor) complexes, known as PGL granules, from somatic cells during
      embryogenesis. Autophagic degradation of the PGL granule scaffold protein EPG-2
      and other protein aggregates was unaffected in epg-11/prmt-1 mutants. Loss of epg
      11/prmt-1 activity impairs the association of PGL granules with EPG-2 and LGG-1
      puncta. EPG-11/PRMT-1 directly methylates arginines in the RGG domains of PGL-1
      and PGL-3. Autophagic removal of PGL proteins is impaired when the methylated
      arginines are mutated. Our study reveals that posttranslational arginine
      methylation regulates the association of the cargo-receptor complex with the
      scaffold protein, providing a mechanism for modulating degradation efficiency in
      selective autophagy.

PMID- 24140421
TI  - VprBP has intrinsic kinase activity targeting histone H2A and represses gene
      transcription.
AB  - Histone modifications play important roles in the regulation of gene expression
      and chromatin organization. VprBP has been implicated in transcriptionally silent
      chromatin formation and cell-cycle regulation, but the molecular basis underlying
      such effects remains unclear. Here we report that VprBP possesses an intrinsic
      protein kinase activity and is capable of phosphorylating histone H2A on
      threonine 120 (H2AT120p) in a nucleosomal context. VprBP is localized to a large
      set of tumor suppressor genes and blocks their transcription, in a manner that is
      dependent on its kinase activity toward H2AT120. The functional significance of
      VprBP-mediated H2AT120p is further underscored by the fact that RNAi knockdown
      and small-molecule inhibition of VprBP reactivate growth regulatory genes and
      impede tumor growth. Our findings establish VprBP as a major kinase responsible
      for H2AT120p in cancer cells and suggest that VprBP inhibition could be a new
      strategy for the development of anticancer therapeutics. 

PMID- 24140422
TI  - Stochastic ERK activation induced by noise and cell-to-cell propagation regulates
      cell density-dependent proliferation.
AB  - The extracellular signal-regulated kinase (ERK) plays a central role in the
      signaling cascades of cell growth. Here, we show that stochastic ERK activity
      pulses regulate cell proliferation rates in a cell density-dependent manner. A
      fluorescence resonance energy transfer (FRET) biosensor revealed that stochastic
      ERK activity pulses fired spontaneously or propagated from adjacent cells.
      Frequency, but not amplitude, of ERK activity pulses exhibited a bell-shaped
      response to the cell density and correlated with cell proliferation rates.
      Consistently, synthetic ERK activity pulses generated by a light-switchable CRaf
      protein accelerated cell proliferation. A mathematical model clarified that 80%
      and 20% of ERK activity pulses are generated by the noise and cell-to-cell
      propagation, respectively. Finally, RNA sequencing analysis of cells subjected to
      the synthetic ERK activity pulses suggested the involvement of serum responsive
      factor (SRF) transcription factors in the gene expression driven by the ERK
      activity pulses.

PMID- 24140423
TI  - Novel test of motor and other dysfunctions in mouse neurological disease models.
AB  - BACKGROUND: Just like human neurological disorders, corresponding mouse models
      present multiple deficiencies. Estimating disease progression or potential
      treatment effectiveness in such models necessitates the use of time consuming and
      multiple tests usually requiring a large number of scarcely available genetically
      modified animals. NEW METHOD: Here we present a novel and simple single camera
      arrangement and analysis software for detailed motor function evaluation in mice
      walking on a wire mesh that provides complex 3D information (instantaneous
      position, speed, distance traveled, foot fault depth, duration, location,
      relationship to speed of movement, etc.). RESULTS: We investigated 3 groups of
      mice with various neurological deficits: (1) unilateral motor cortical stroke;
      (2) effects of moderate ethanol doses; and (3) aging (96-99 weeks old). We show
      that post stroke recovery can be divided into separate stages based on strikingly
      different characteristics of motor function deficits, some resembling the human
      motor neglect syndrome. Mice treated with moderate dose of alcohol and aged mice
      showed specific motor and exploratory deficits. COMPARISON WITH EXISTING METHODS:
      Other tests rely either partially or entirely on manual video analysis
      introducing a significant subjective component into the analysis, and analyze a
      single aspect of motor function. CONCLUSIONS: Our novel experimental approach
      provides qualitatively new, complex information about motor impairments and
      locomotor/exploratory activity. It should be useful for the detailed
      characterization of a broad range of human neurological disease models in mice,
      and for the more accurate assessment of disease progression or treatment
      effectiveness.

PMID- 24140424
TI  - To change or not to change... what should we do with recalled leads?

PMID- 24140425
TI  - MAST2 and NOTCH1 translocations in breast carcinoma and associated pre-invasive
      lesions.
AB  - There are several mutations and structural variations common to breast cancer.
      Many of these genomic changes are thought to represent driver mutations in
      oncogenesis. Less well understood is how and when these changes take place in
      breast cancer development. Previous studies have identified gene rearrangements
      in the microtubule-associated serine-threonine kinase (MAST) and NOTCH gene
      families in 5% to 7% of invasive breast cancers. Some of these translocations can
      be detected by fluorescence in situ hybridization (FISH) allowing for examination
      of the correlation between these genomic changes and concurrent morphologic
      changes in early breast neoplasia. NOTCH and MAST gene rearrangements were
      identified by FISH in a large series of breast cancer cases organized on tissue
      microarrays (TMA). When translocations were identified by TMA, we performed full
      cross-section FISH to evaluate concurrent pre-invasive lesions. FISH break-apart
      assays were designed for NOTCH1 and MAST2 gene rearrangements. Translocations
      were identified in 16 cases of invasive carcinoma; 10 with MAST2 translocations
      (2.0%) and 6 cases with NOTCH1 translocations (1.2%). Whole section FISH analysis
      of these cases demonstrated that the translocations are present in the majority
      of concurrent ductal carcinoma in situ (DCIS) (6/8). When DCIS wasn't associated
      with an invasive component, it was never translocated (0/170, P=.0048). We have
      confirmed the presence of MAST and NOTCH family gene rearrangements in invasive
      breast carcinoma, and show that FISH studies can effectively be used with TMAs to
      screen normal, pre-invasive, and coexisting invasive disease. Our findings
      suggest that these translocations occur during the transition to DCIS and/or
      invasive carcinoma. 

PMID- 24140426
TI  - The dopamine D1 receptor agonist SKF 38393 improves temporal order memory
      performance in maternally deprived rats.
AB  - Previously, we showed that maternal deprivation (MD) (3h/day, postnatal-day 1-14)
      impaired the performance at adulthood in the object temporal order memory task
      (TMT) that principally implicates the medial prefrontal cortex (mPFC). Dopamine
      (DA) transmission in the PFC may play a critical role in the achievement of the
      TMT. Here, to investigate whether MD could results in dysfunction of the DA
      system in the mPFC, we assessed in this region the tissue contents and
      extracellular levels of DA and its metabolites, as the density of D1 receptor.
      Besides we examined whether an agonist of the DA receptor D1, the SKF38393, could
      have a beneficial effect on the performance of deprived (D) rats in the TMT. We
      observed that MD induced a significant reduction of the extracellular level of
      DOPAC in the mPFC and in the density of the D1 receptor in the anterior cingulate
      cortex, a sub-region of mPFC. On the other hand, we observed that an acute
      systemic injection of a D1 receptor agonist, SKF38393, was effective to correct
      the memory deficiency of D rats in the TMT, when administered before the
      retrieval phase. We showed that a stress suffered by rats during the perinatal
      period led to dysfunction of the adult DA system, possibly triggering greater
      vulnerability to cognitive and mood disorders. Interestingly, an acute
      administration of a D1 receptor agonist in adulthood was sufficient to improve
      the deficit in the temporal memory. A better understanding of this phenomenon
      would permit the development of treatments adapted to patients with a history of
      early traumatic experiences. 

PMID- 24140427
TI  - Adult Ovenbirds (Seiurus aurocapilla) show increased stress-responsiveness in
      logged forests.
AB  - Forest harvesting is a form of anthropogenic disturbance, yet the effects of such
      disturbance on the endocrine physiology of wildlife have been infrequently
      studied. We investigated the effect of two methods of forest harvesting
      ('intensive' and 'typical' group-selection silviculture) and un-harvested control
      sites on the glucocorticoid levels of adult Ovenbirds (Seiurus aurocapilla), a
      forest interior bird species. We collected blood samples from adult males
      immediately after capture to examine baseline corticosterone, and then following
      a standardized capture and restraint protocol, to examine stress-induced levels.
      There was no significant repeatability in either baseline or stress-induced
      corticosterone levels for eleven individuals measured in both years of study.
      Despite no differences across harvesting treatments in male body mass or baseline
      corticosterone levels, males captured in sites subjected to intensive harvesting
      had significantly higher stress-induced corticosterone levels than males in other
      treatments. Currently, the mechanism driving differences in stress-reactivity is
      unknown although we hypothesize that the size of gaps resulting from intensive
      group-selection silviculture may increase perceived predation risk. In comparison
      to our previous work on nestling Ovenbirds, adults respond differently to stress
      from group-selection silviculture. 

PMID- 24140428
TI  - Different amounts of ejaculatory activity, a natural rewarding behavior, induce
      differential mu and delta opioid receptor internalization in the rat's ventral
      tegmental area.
AB  - Opioid receptors internalize upon specific agonist stimulation. The in vivo
      significance of receptor internalization is not well established, partly due to
      the limited in vivo models used to study this phenomenon. Ejaculation promotes
      endogenous opioid release which activates opioid receptors at the brain,
      including the mesolimbic system and medial preoptic area. The objective of the
      present work was to analyze if there was a correlation between the degree of in
      vivo mu (MOR) and delta opioid receptor (DOR) internalization in the ventral
      tegmental area and the execution of different amounts of ejaculatory behavior of
      male rats. To this aim, we analyzed the brains of rats that ejaculated once or
      six successive times and of sexually exhausted rats with an established sexual
      inhibition, using immunofluorescence and confocal microscopy. Results showed that
      MOR and DOR internalization increased as a consequence of ejaculation. There was
      a relationship between the amount of sexual activity executed and the degree of
      internalization for MOR, but not for DOR. MOR internalization was larger in rats
      that ejaculated repeatedly than in animals ejaculating only once. Significant DOR
      internalization was found only in animals ejaculating once. Changes in MOR, DOR
      and beta arrestin2 detection, associated to sexual activity, were also found. It
      is suggested that copulation to satiety might be useful as a model system to
      study the biological significance of receptor internalization. 

PMID- 24140430
TI  - Levels of 5-methyltetrahydrofolate and ascorbic acid in cerebrospinal fluid are
      correlated: implications for the accelerated degradation of folate by reactive
      oxygen species.
AB  - Deficiency of 5-methyltetrahydrofolate (5-MTHF) in cerebrospinal fluid (CSF) is
      associated with a number of neurometabolic conditions including mitochondrial
      electron transport chain defects. Whilst failure of the active transport of 5
      methyltetrahydrofolate (5-MTHF) into the CSF compartment has been proposed as a
      potential mechanism responsible for the 5-MTHF deficiency seen in mitochondrial
      disorders, it is becoming increasingly clear that other mechanisms are involved.
      Here, we have considered the role of oxidative stress as a contributing
      mechanism. Concerning, ascorbic acid (AA), we have established a CSF reference
      range (103-303MUM) and demonstrated a significant positive correlation between 5
      MTHF and AA. Furthermore, CSF itself was also shown to convey antioxidant
      properties towards 5-MTHF. However, this protection could be overcome by the
      introduction of a hydroxyl radical generating system. Using a neuronal model
      system, inhibition of mitochondrial complex I, by 58%, was associated with a 23%
      increase in superoxide generation and a significantly increased loss of 5-MTHF
      from the extracellular medium. Addition of AA (150MUM) was able to prevent this
      increased 5-MTHF catabolism. We conclude that increased generation of reactive
      oxygen species and/or loss of CSF antioxidants are also factors to consider with
      regard to the development of a central 5-MTHF deficiency. Co-supplementation of
      AA together with appropriate folate replacement may be of therapeutic benefit. 

PMID- 24140429
TI  - Moving beyond energy homeostasis: new roles for glucagon-like peptide-1 in food
      and drug reward.
AB  - Glucagon-like peptide-1 (GLP-1), a hormone and neuropeptide, is known to regulate
      energy homeostasis in part through an established central role in controlling
      food intake. Historically this central role has largely been attributed to GLP-1
      receptor signaling in the brainstem and hypothalamus. However, emerging data
      indicate that GLP-1 also contributes to non-homeostatic regulation of food reward
      and motivated behaviors in brain reward centers, including the ventral tegmental
      area and nucleus accumbens. The hypothesis that GLP-1 signaling modulates reward
      circuitry has provided the impetus for studies demonstrating that GLP-1
      attenuates reward for psychostimulants and alcohol. Here, we examine current
      evidence for GLP-1-mediated regulation of food and drug reward and use these
      findings to hypothesize mechanisms of action within brain reward centers. 

PMID- 24140431
TI  - Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D
      aspartate receptor subunits and D-serine.
AB  - The influence of the gut microbiota on brain chemistry has been convincingly
      demonstrated in rodents. In the absence of gut bacteria, the central expression
      of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor
      (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and
      impart significant anxiolytic effects. We tested whether prebiotic compounds,
      which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs.
      In addition, we examined whether plasma from prebiotic treated rats released BDNF
      from human SH-SY5Y neuroblastoma cells, to provide an initial indication of
      mechanism of action. Rats were gavaged with fructo-oligosaccharides (FOS),
      galacto-oligosaccharides (GOS) or water for five weeks, prior to measurements of
      brain BDNF, NMDAR subunits and amino acids associated with glutamate
      neurotransmission (glutamate, glutamine, and serine and alanine enantiomers).
      Prebiotics increased hippocampal BDNF and NR1 subunit expression relative to
      controls. The intake of GOS also increased hippocampal NR2A subunits, and frontal
      cortex NR1 and d-serine. Prebiotics did not alter glutamate, glutamine, l-serine,
      l-alanine or d-alanine concentrations in the brain, though GOSfeeding raised
      plasma d-alanine. Elevated levels of plasma peptide YY (PYY) after GOS intake was
      observed. Plasma from GOS rats increased the release of BDNF from SH-SY5Y cells,
      but not in the presence of PYY antisera. The addition of synthetic PYY to SH-SY5Y
      cell cultures, also elevated BDNF secretion. We conclude that prebiotic-mediated
      proliferation of gut microbiota in rats, like probiotics, increases brain BDNF
      expression, possibly through the involvement of gut hormones. The effect of GOS
      on components of central NMDAR signalling was greater than FOS, and may reflect
      the proliferative potency of GOS on microbiota. Our data therefore, provide a
      sound basis to further investigate the utility of prebiotics in the maintenance
      of brain health and adjunctive treatment of neuropsychiatric disorders. 

PMID- 24140432
TI  - An LDLa domain-containing C-type lectin is involved in the innate immunity of
      Eriocheir sinensis.
AB  - C-type lectins (CTLs) have crucial functions in recognizing and eliminating
      pathogens in innate immunity. This study identified a novel low-density
      lipoprotein receptor class A (LDLa) domain-containing CTL, designated as
      EsCTLDcp, from the Chinese mitten crab Eriocheir sinensis. The EsCTLDcp cDNA is
      1258 bp long, with a 975 bp open reading frame that encodes a 324-amino acid
      protein. EsCTLDcp contains a signal peptide, an LDLa, and a single C-type lectin
      like domain. EsCTLDcp was only expressed in the hepatopancreas of normal crabs,
      and its expression was regulated following crab challenge with pathogen
      associated molecular patterns and with bacteria. The recombinant EsCTLDcp
      agglutinates Gram-positive (Staphylococcus aureus) and Gram-negative bacteria
      (Vibrio parahaemolyticus and Aeromonas hydrophila) in the presence of calcium.
      rEsCTLDcp also binds to various bacteria including S. aureus, Bacillus
      thuringiensis, Bacillus subtilis, Escherichia coli, Vibrio natriegens, V.
      parahaemolyticus, and A. hydrophila. The rEsCTLDcp protein helped the crabs clear
      the virulent Gram-negative bacterium V. parahaemolyticus in vivo, as well as
      interacted with VP24, an envelope protein of white spot syndrome virus (WSSV).
      These data suggest that EsCTLDcp functions as a pattern-recognition receptor
      involved in the innate immunity of E. sinensis.

PMID- 24140433
TI  - Effects of portal hypertension on contractility of rat spleen.
AB  - Portal hypertension induces changes in vascular responses to vasoconstrictors.
      However, the effects of portal hypertension on splenic contraction have not
      previously been investigated. In partial portal vein ligated (PVL) and sham
      operated rats, we examined the splenic contractile responses to cumulative
      concentrations of noradrenaline and KCl. In PVL rats, the potency of
      noradrenaline in producing splenic contraction was significantly increased (pEC50
      of 5.88 +/- 0.08), as compared to sham (5.40 +/- 0.06; p<0.001). In the presence
      of prazosin (10(-8)M), there was a significant rightward shift in the
      noradrenaline concentration response curve but the shift was greater for PVL, so
      that in the presence of prazosin there was no significant difference between PVL
      and sham animals in the potency of noradrenaline. Prazosin produced a
      significantly greater shift of noradrenaline potency in spleen from PVL (pKB of
      8.88 +/- 0.06) (n=6) than from sham animals (8.51 +/- 0.08, n=6), demonstrating
      that the alpha1-adrenoceptor mediated component is greater in spleen from PVL. In
      the presence of prazosin (10(-8)M) the residual response is non-alpha1
      adrenoceptor mediated, presumably alpha2-adrenoceptor mediated, and this response
      did not differ between sham and PVL. The maximum splenic contraction did not
      significantly differ between sham and PVL rats for either agonist. In conclusion,
      noradrenaline potency in contracting the rat spleen was significantly increased
      in tissues from PVL rats. The increased potency of prazosin suggests a greater
      predominance of alpha1-adrenoceptors in spleen of PVL rats, as prazosin has lower
      potency at alpha2-adrenoceptors.

PMID- 24140434
TI  - Effects of cannabidiol on the function of alpha7-nicotinic acetylcholine
      receptors.
AB  - The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis
      plant, on the function of the cloned alpha7 subunit of the human nicotinic
      acetylcholine (alpha7 nACh) receptor expressed in Xenopus oocytes were tested
      using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh
      (100 MUM)-induced currents with an IC50 value of 11.3 uM. Other phytocannabinoids
      such as cannabinol and Delta(9)-tetrahydrocannabinol did not affect ACh-induced
      currents. CBD inhibition was not altered by pertussis toxin treatment. In
      addition, CBD did not change GTP-gamma-S binding to the membranes of oocytes
      injected with alpha7 nACh receptor cRNA. The effect of CBD was not dependent on
      the membrane potential. CBD (10 uM) did not affect the activity of endogenous
      Ca(2+)-dependent Cl(-) channels, since the extent of inhibition by CBD was
      unaltered by intracellular injection of the Ca(2+) chelator BAPTA and perfusion
      with Ca(2+)-free bathing solution containing 2mM Ba(2+). Inhibition by CBD was
      not reversed by increasing ACh concentrations. Furthermore, specific binding of
      [(125)I] alpha-bungarotoxin was not inhibited by CBD (10 uM) in oocytes
      membranes. Using whole cell patch clamp technique in CA1 stratum radiatum
      interneurons of rat hippocampal slices, currents induced by choline, a selective
      agonist of alpha7-receptor induced currents were also recoded. Bath application
      of CBD (10 uM) for 10 min caused a significant inhibition of choline induced
      currents. Finally, in hippocampal slices, [(3)H] norepinephrine release evoked by
      nicotine (30 uM) was also inhibited by 10 uM CBD. Our results indicate that CBD
      inhibits the function of the alpha7-nACh receptor.

PMID- 24140435
TI  - Long-lasting physiological antagonism of calcitonin gene-related peptide towards
      endothelin-1 in rat mesenteric arteries and human coronary arteries.
AB  - Endothelin-1 causes long-lasting contraction via endothelin type A receptor
      (ETAR) in isolated rat mesenteric arteries (RMA) that cannot be readily
      terminated by removing the agonist, or by adding the ETAR antagonist BQ123 or the
      NO donor sodium nitroprusside. It could be terminated by adding calcitonin-gene
      related peptide (CGRP), most likely because CGRP causes ET-1/ETAR dissociation.
      Here we investigated this phenomenon in human coronary microarteries (HCMA). We
      simultaneously verified the effects of CGRP in RMA and HCMA towards other
      vasoconstrictors, i.e., the alpha1-adrenoceptor agonist phenylephrine, the
      thromboxane A2 analog U46619 (9,11-dideoxy-11alpha,9alpha-epoxy-methano
      prostaglandin F2alpha) and KCl. Long-lasting contraction (remaining after washing
      away the agonist) was observed for ET-1 in RMA, but not HCMA. Constrictions to
      phenylephrine, U46619 or KCl did not last upon washing. When added on top of ET-1
      initiated contraction in RMA, CGRP effectively counteracted vasoconstriction,
      i.e., it caused full relaxation. Inhibitory effects of CGRP were also observed
      when briefly exposing RMA and HCMA to CGRP 1h before the addition of ET-1.
      Similar inhibitory effects of transient CGRP pre-incubation were seen towards
      phenylephrine, U46619 or KCl in RMA and HCMA. In conclusion, our data imply that
      CGRP, like ET-1, causes long-lasting effects that remain apparent up to 1h after
      its removal from the organ bath. Thus, in addition to the reported dissociation
      of ET-1/ETAR complexes, CGRP causes long-lasting non-selective arterial smooth
      muscle relaxation that may add to the neuropeptide being a physiological
      antagonist of arterial effects of ET-1. Long-lasting, washout-resistant ET-1/ETAR
      interaction does not occur in HCMAs. 

PMID- 24140436
TI  - Calcium influx through L-type channels attenuates skeletal muscle contraction via
      inhibition of adenylyl cyclases.
AB  - Skeletal muscle contraction is triggered by acetylcholine induced release of
      Ca(2+) from sarcoplasmic reticulum. Although this signaling pathway is
      independent of extracellular Ca(2+), L-type voltage-gated calcium channel (Cav)
      blockers have inotropic effects on frog skeletal muscles which occur by an
      unknown mechanism. Taking into account that skeletal muscle fiber expresses
      Ca(+2)-sensitive adenylyl cyclase (AC) isoforms and that cAMP is able to increase
      skeletal muscle contraction force, we investigated the role of Ca(2+) influx on
      mouse skeletal muscle contraction and the putative crosstalk between
      extracellular Ca(2+) and intracellular cAMP signaling pathways. The effects of
      Cav blockers (verapamil and nifedipine) and extracellular Ca(2+) chelator EGTA
      were evaluated on isometric contractility of mouse diaphragm muscle under direct
      electrical stimulus (supramaximal voltage, 2 ms, 0.1 Hz). Production of cAMP was
      evaluated by radiometric assay while Ca(2+) transients were assessed by confocal
      microscopy using L6 cells loaded with fluo-4/AM. Ca(2+) channel blockers
      verapamil and nifedipine had positive inotropic effect, which was mimicked by
      removal of extracellular Ca(+2) with EGTA or Ca(2+)-free Tyrode. While
      phosphodiesterase inhibitor IBMX potentiates verapamil positive inotropic effect,
      it was abolished by AC inhibitors SQ22536 and NYK80. Finally, the inotropic
      effect of verapamil was associated with increased intracellular cAMP content and
      mobilization of intracellular Ca(2+), indicating that positive inotropic effects
      of Ca(2+) blockers depend on cAMP formation. Together, our results show that
      extracellular Ca(2+) modulates skeletal muscle contraction, through inhibition of
      Ca(2+)-sensitive AC. The cross-talk between extracellular calcium and cAMP
      dependent signaling pathways appears to regulate the extent of skeletal muscle
      contraction responses.

PMID- 24140438
TI  - Pro-oxidative synergic bactericidal effect of NO: kinetics and inhibition by
      nitroxides.
AB  - NO plays diverse roles in physiological and pathological processes, occasionally
      resulting in opposing effects, particularly in cells subjected to oxidative
      stress. NO mostly protects eukaryotes against oxidative injury, but was
      demonstrated to kill prokaryotes synergistically with H2O2. This could be a
      promising therapeutic avenue. However, recent conflicting findings were reported
      describing dramatic protective activity of NO. The previous studies of NO effects
      on prokaryotes applied a transient oxidative stress while arbitrarily checking
      the residual bacterial viability after 30 or 60min and ignoring the process
      kinetics. If NO-induced synergy and the oxidative stress are time-dependent, the
      elucidation of the cell killing kinetics is essential, particularly for survival
      curves exhibiting a "shoulder" sometimes reflecting sublethal damage as in the
      linear-quadratic survival models. We studied the kinetics of NO synergic effects
      on H2O2-induced killing of microbial pathogens. A synergic pro-oxidative activity
      toward gram-negative and gram-positive cells is demonstrated even at sub-MUM/min
      flux of NO. For certain strains, the synergic effect progressively increased with
      the duration of cell exposure, and the linear-quadratic survival model best fit
      the observed survival data. In contrast to the failure of SOD to affect the
      bactericidal process, nitroxide SOD mimics abrogated the pro-oxidative synergy of
      NO/H2O2. These cell-permeative antioxidants, which hardly react with diamagnetic
      species and react neither with NO nor with H2O2, can detoxify redox-active
      transition metals and catalytically remove intracellular superoxide and nitrogen
      derived reactive species such as (*)NO2 or peroxynitrite. The possible mechanism
      underlying the bactericidal NO synergy under oxidative stress and the potential
      therapeutic gain are discussed. 

PMID- 24140439
TI  - Head and neck cutaneous squamous cell carcinoma metastatic to cervical sublevel
      IIb lymph nodes occurred from primary sites involving the auricle and adjacent
      neck.
AB  - PURPOSE: Neck dissections that include sublevel IIb increase the risk of
      postoperative shoulder dysfunction. The purpose of this investigation was to
      document the incidence of level IIb metastatic lymphatic spread in a group of
      patients undergoing neck dissection as part of the surgical management of
      cutaneous squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: A
      retrospective review of the pathology records taken from 1 surgeon from June 2006
      through June 2013 was carried out. The predictor variable was the primary tumor
      site. The outcome variable was the metastatic nodal involvement according to neck
      level and sublevel. Secondary variables included T stage, pathologist, tumor
      depth, and the presence of perineural, perilymphatic, and perivascular invasion.
      Data analyses were by descriptive statistics. RESULTS: Thirty-six patients with a
      total of 40 neck dissections met the inclusion criteria. The average primary site
      tumor depth was 14.7 mm, and there were 16 cases of poorly differentiated
      squamous cell carcinoma. Sublevel IIb was involved in 7.5% of cases, all of which
      occurred from lateralized primary sites of the head and neck. CONCLUSIONS:
      Cutaneous squamous cell carcinoma arising from the auricle and neck sites
      adjacent to sublevel IIb may have increased risk of metastatic involvement of
      sublevel IIb nodes. Further studies with larger numbers are required to determine
      the risk of metastasis to sublevel IIb from midline sites of the face.

PMID- 24140440
TI  - Which physical activities and sports can be recommended to chronic low back pain
      patients after rehabilitation?
AB  - BACKGROUND: Physical exercise is widely prescribed in rehabilitation programmes
      for low back pain (LBP). The LBP patient often asks whether this physical
      activity should be maintained and, in some cases, whether he/she should resume or
      take up a sport. PURPOSE: To answer these two questions by performing a review of
      literature on the efficacy and safety of post-rehabilitation physical activities
      and sport in LBP. METHOD: A systematic search of computerized databases from 1990
      to 2011 was performed using grade 1 to 4 studies articles in English or French.
      RESULTS: Of the 2583 initially identified articles, 121 articles were analysed.
      Globally, physical activities like swimming, walking and cycling, practiced at
      moderate-intensity help to maintain fitness and control pain. Inconsistent
      results were found for avoiding recommendations according to the nature of PA.
      Sport activities, except ballgames, can be easily resume or take up as tennis,
      horse riding, martial arts, gymnastics, golf and running which can be performed
      at a lower intensity or lower competitive level. DISCUSSION AND CONCLUSION:
      Moderate but regular physical activity helps to improve fitness and does not
      increase the risk of acute pain in chronic LBP patients. The resumption of a
      sport may require a number of adaptations; dialogue between the therapist and the
      sports trainer is therefore recommended.

PMID- 24140437
TI  - Regulation of keratinocyte expression of stress proteins and antioxidants by the
      electrophilic nitrofatty acids 9- and 10-nitrooleic acid.
AB  - Nitric oxide and various by-products including nitrite contribute to tissue
      injury by forming novel intermediates via redox-mediated nitration reactions.
      Nitration of unsaturated fatty acids generates electrophilic nitrofatty acids
      such as 9-nitrooleic acid (9-NO) and 10-nitrooleic acid (10-NO), which are known
      to initiate intracellular signaling pathways. In these studies, we characterized
      nitrofatty acid-induced signaling and stress protein expression in mouse
      keratinocytes. Treatment of keratinocytes with 5-25MUM 9-NO or 10-NO for 6h
      upregulated mRNA expression of heat shock proteins (hsp's) 27 and 70; primary
      antioxidants heme oxygenase-1 (HO-1) and catalase; secondary antioxidants
      glutathione S-transferase (GST) A1/2, GSTA3, and GSTA4; and Cox-2, a key enzyme
      in prostaglandin biosynthesis. The greatest responses were evident with HO-1,
      hsp27, and hsp70. In keratinocytes, 9-NO activated JNK and p38 MAP kinases. JNK
      inhibition suppressed 9-NO-induced HO-1, hsp27, and hsp70 mRNA and protein
      expression, whereas p38 MAP kinase inhibition suppressed HO-1. In contrast,
      inhibition of constitutive expression of Erk1/2 suppressed only hsp70, indicating
      that 9-NO modulates expression of stress proteins by distinct mechanisms. 9-NO
      and 10-NO also upregulated expression of caveolin-1, the major structural
      component of caveolae. Western blot analysis of caveolar membrane fractions
      isolated by sucrose density centrifugation revealed that HO-1, hsp27, and hsp70
      were localized within caveolae after nitrofatty acid treatment of keratinocytes,
      suggesting a link between induction of stress response proteins and caveolin-1
      expression. These data indicate that nitrofatty acids are effective signaling
      molecules in keratinocytes. Moreover, caveolae seem to be important in the
      localization of stress proteins in response to nitrofatty acids. 

PMID- 24140441
TI  - Effect of rhynchophylline on the expression of p-CREB and sc-Fos in triatum and
      hippocampal CA1 area of methamphetamine-induced conditioned place preference
      rats.
AB  - To explore the effect of rhynchophylline (Rhy) on the expression of p-CREB and c
      Fos in the striatum and hippocampal CA1 area of methamphetamine-induced
      conditioned place preference (CPP) rat, methamphetamine (2 mg/kg) was injected to
      rats and the conditioned place preference was observed in these rats treated with
      or without Rhy. An immunohistochemistry assay was used to determine the
      expression of p-CREB and c-Fos in the striatum and hippocampal CA1 area.
      Methamphetamine induced significant behavior alteration in CPP, while after
      pretreatment with rhynchophylline or ketamine, the time of staying in
      methamphetamine-paired compartment of rats was significantly reduced.
      Methamphetamine also increased the number of p-CREB positive cells in the
      striatum and hippocampal CA1 zone, as well as p-Fos positive cells. However, the
      compound Rhy could attenuate the effect. These findings show that Rhy can
      suppress the acquisition of CPP in rats induced by methamphetamine and the action
      may be related with the reduced expression of p-CREB and p-Fos in the striatum
      and hippocampus.

PMID- 24140443
TI  - Opioids and restless legs syndrome.

PMID- 24140442
TI  - Prolonged release oxycodone-naloxone for treatment of severe restless legs
      syndrome after failure of previous treatment: a double-blind, randomised, placebo
      controlled trial with an open-label extension.
AB  - BACKGROUND: Opioids are a potential new treatment for severe restless legs
      syndrome. We investigated the efficacy and safety of a fixed-dose combination of
      prolonged release oxycodone-naloxone for patients with severe restless legs
      syndrome inadequately controlled by previous, mainly dopaminergic, treatment.
      METHODS: This multicentre study consisted of a 12-week randomised, double-blind,
      placebo-controlled trial and 40-week open-label extension phase done at 55 sites
      in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6
      months and an International RLS Study Group severity rating scale sum score of at
      least 15; patients with severe chronic obstructive pulmonary disease or a history
      of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to
      either study drug or matched placebo with a validated interactive response
      technology system in block sizes of four. Study drug was oxycodone 5.0 mg,
      naloxone 2.5 mg, twice per day, which was up-titrated according to investigator's
      opinion to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day; in the
      extension, all patients started on oxycodone 5.0 mg, naloxone 2.5 mg, twice per
      day, which was up-titrated to a maximum of oxycodone 40 mg, naloxone 20 mg, twice
      per day. The primary outcome was mean change in severity of symptoms according to
      the International RLS Study Group severity rating scale sum score at 12 weeks.
      This study is registered with ClinicalTrials.gov (number NCT01112644) and with
      EudraCT (number 2009-011107-23). FINDINGS: We screened 495 patients, of whom 306
      were randomly assigned and 276 included in the primary analysis (132 to prolonged
      release oxycodone-naloxone vs 144 to placebo). 197 patients participated in the
      open-label extension. Mean International RLS Study Group rating scale sum score
      at randomisation was 31.6 (SD 4.5); mean change after 12 weeks was -16.5 (SD
      11.3) in the prolonged release oxycodone-naloxone group and -9.4 (SD 10.9) in the
      placebo group (mean difference between groups at 12 weeks 8.15, 95% CI 5.46
      10.85; p<0.0001). After the extension phase, mean sum score was 9.7 (SD 7.8).
      Treatment-related adverse events occurred in 109 of 150 (73%) patients in the
      prolonged release oxycodone-naloxone group and 66 of 154 (43%) in the placebo
      group during the double-blind phase; during the extension phase, 112 of 197 (57%)
      had treatment-related adverse events. Five of 306 (2%) patients had serious
      treatment-related adverse events when taking prolonged release oxycodone-naloxone
      (vomiting with concurrent duodenal ulcer, constipation, subileus, ileus, acute
      flank pain). INTERPRETATION: Prolonged release oxycodone-naloxone was efficacious
      for short-term treatment of patients with severe restless legs syndrome
      inadequately controlled with previous treatment and the safety profile was as
      expected. Our study also provides evidence of open-label long-term efficacy of
      this treatment. Opioids can be used to treat patients with severe restless legs
      syndrome who have had no benefit with first-line drugs. FUNDING: Mundipharma
      Research.

PMID- 24140444
TI  - Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands
      for Alzheimer's disease.
AB  - The anti-amyloid properties shared by several quinones inspired the design of a
      new series of hybrids derived from the multi-target drug candidate memoquin (1).
      The hybrids consist of a central benzoquinone core and a fragment taken from non
      steroidal anti-inflammatory drugs, connected through polyamine linkers. The new
      hybrids retain the potent anti-aggregating activity of the parent 1, while
      exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)
      6 were Abeta aggregation inhibitors even more potent than 1. The balanced
      amyloid/cholinesterase inhibitory profile is an added value that makes the
      present series of compounds promising leads against Alzheimer's disease. 

PMID- 24140445
TI  - Selenium nanoparticles induced membrane bio-mechanical property changes in MCF-7
      cells by disturbing membrane molecules and F-actin.
AB  - Selenium nanoparticles (Se NPs) have been served as promising materials for
      biomedical applications, especially for cancer treatment. The anti-cancer effects
      of Se NPs against cancer cells have been widely studied in recent years, but
      whether Se NPs can induce the changes of cell membrane bio-mechanical properties
      in cancer cells still remain unexplored. In this Letter, we prepared Se NPs for
      investigating the intracellular localization of Se NPs in MCF-7 cells and
      determined the effects of Se NPs on apoptosis and necrosis in MCF-7 cells.
      Especially, we reported for the first time about the effects of Se NPs on the bio
      mechanical properties of cancer cells and found that Se NPs could remarkably
      decrease the adhesion force and Young's modulus of MCF-7 cells. To further
      understand the potential mechanisms about how Se NPs affect the bio-mechanical
      properties of MCF-7 cells, we also investigated the expression of CD44 molecules,
      the structure and the amounts of F-actin. The results indicated that the
      decreased adhesion force between AFM tip and cell membrane was partially due to
      the changes of membrane molecules induced by Se NPs, such as the down-regulation
      of trans-membrane CD44 molecules. Additionally, the decrease of Young's modulus
      of MCF-7 cells was due to the dis-organization and down-regulation of F-actin
      induced by Se NPs. These results collectively suggested that cell membrane was of
      vital importance in Se NPs induced toxicity in cancer cells, which could be
      served as a potential target for cancer treatment by Se NPs. 

PMID- 24140446
TI  - GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in
      vitro profile and in vivo analgesic efficacy.
AB  - We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole,
      as GluK1 antagonists with potential as oral analgesics. We have established the
      optimal linker atom between decahydroisoquinoline and phenyl rings and
      demonstrated an improvement of both the affinity for the GluK1 receptor and the
      selectivity against the related GluA2 receptor with proper phenyl substitution.
      In this Letter, we also disclose in vivo data that led to the discovery of
      LY545694.HCl, a compound with oral efficacy in two persistent pain models. 

PMID- 24140447
TI  - Synthesis and evaluation of N-alkyl-S-[3-(piperidin-1-yl)propyl]isothioureas:
      high affinity and human/rat species-selective histamine H(3) receptor
      antagonists.
AB  - S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were
      synthesized in the search for novel nonimidazole histamine H3 receptor (H3R)
      antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas
      18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic
      activities against in vitro human H3R, but were inactive against in vitro human
      H4R. Furthermore, three alkyl homologs 18-20 showed inactivity for histamine
      release in in vivo rat brain microdialysis, suggesting differences in antagonist
      affinities between species. In addition, in silico docking studies of N-[4-(4
      chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter
      homolog 17 with human/rat H3Rs revealed that structural differences between the
      antagonist-docking cavities of rat and human H3Rs were likely caused by the
      Ala122/Val122 mutation. 

PMID- 24140448
TI  - [Pain behaviour indicator scale (ESCID) application in severe non-communicative
      trauma patients receiving mechanical ventilation].
AB  - OBJECTIVE: To assess pain in non-communicative patients with severe trauma
      undergoing mechanical ventilation prior to, during and after tracheal suctioning,
      mobilization and wound care. MATERIAL AND METHOD: A prospective and observational
      study from October to December 2011 was performed. Study variables were ESCID
      scale and monitoring of vital signs (blood pressure, heart rate, and respiratory
      rate). Data were gathering 5 minutes before, during and 15 minutes after the 3
      procedures. The nursing evolutive report recorded pain assessment, administration
      and effectiveness of the analgesia. Descriptive analysis of variables included
      Student's T test/ANOVA for multivariate analysis with SPSS 17.0. RESULTS: A
      hundred eighty four observations: 46.8% tracheal suctioning, 38.5% mobilization
      and 14.7% wound care were performed in 29 patients. ESCID score was 0.4+/-1
      before, 3.4+/-2.7 during and 0.4+/-1 after for wound care; 0.4+/-1.1 before,
      3.6+/-2.2 during and 1.1+/-0.5 for tracheal suctioning; 0.5+/-1.1 before, 3+/-2.8
      during and 0.2+/-0.8 after for mobilization. These increased significantly during
      the performance of the 3 procedures before-during/during-after: P=.000. All the
      hemodynamic variables were significantly modified during mobilization and
      tracheal suctioning: before-during/during-after: P=.000, with the exception of
      the cures that only affected respiratory rate. 27% of the procedures received
      analgesia: 9% received it before, 15% during and 3.2% after, with more analgesia
      being required for the wound care (33.3%). The data collected in the nursing
      report on the evaluation of pain/effectiveness of the analgesia showed 20.66%.
      CONCLUSION: An increase on the ESCID score was observed while performing the
      procedures.

PMID- 24140449
TI  - Development and application of a UPLC-MS/MS method for the pharmacokinetic study
      of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats.
AB  - With the purpose to carry out the pharmacokinetic studies of 10-hydroxy
      camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an
      ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)
      method has been developed and validated. The analytes, 10-HCPT and the internal
      standard, Diphenhydramine hydrochloride were extracted with ethyl acetate
      isopropanol (95:5, v/v) and separated on an ACQUITY UPLCTM BEH C18 column using a
      mobile phase composed of acetonitrile and water (containing 0.1% formic acid)
      with a linear gradient program. With positive ion electrospray ionization (ESI),
      the analytes were monitored on a triple quadrupole mass spectrometer in the
      multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained
      over the concentration ranges of 0.5-2500ng/mL. The intra- and inter-day
      precisions were less than 9.8% and 10.8%, respectively. The accuracy was within
      12.1%. The mean recoveries of 10-HCPT at three concentrations of 2.5, 100,
      2000ng/mL were higher than 87.2%. Commercial 10-HCPT injection and 10-HCPT-HES
      conjugate were administered intravenously at an equal dose of 10-HCPT at
      0.5mg/kg. The biological half-life of conjugate was increased significantly from
      10min to 3.15h and the bioavailability was 40 times higher than 10-HCPT
      injection. Consequently, the proposed UPLC-ESI-MS/MS method was proved to be
      sensitive, specific and reliable to analyze 10-HCPT in biological samples; 10
      HCPT and HES conjugate is a promising strategy for delivery of 10-HCPT with
      prolonged half time and improved bioavailability. 

PMID- 24140450
TI  - An automated dual-gradient liquid chromatography-MS/MS method for the
      simultaneous determination of ferulic acid, ligustrazine and ligustilide in rat
      plasma and its application to a pharmacokinetic study.
AB  - An automated on-line SPE and innovative fast polarity switch bioanalysis method
      employing dual-gradient liquid chromatography (DGLC) coupled with mass
      spectrometry (DGLC-MS/MS) was established and validated for the simultaneous
      determination of ferulic acid, ligustrazine and ligustilide in rat plasma after
      administration of Rhizoma Chuanxiong, Angelica sinensis extract or monomer. The
      proteins in plasma samples were precipitated using acetonitrile: methanol (1:1,
      v/v). Sulfamethoxazole was used as an internal standard. The DGLC system contains
      two high-pressure pumps. The first pump was used for on-line solid phase
      extraction with a CycloneTM SPE column. Chromatographic separations were
      performed with the other pump on a Syncronis C18 rapid analytical column. The
      analytical column was eluted by a gradient program that featured an
      acetonitrile/methanol/water gradient (flow-rate, 0.4ml/min). DGLC afforded
      greater convenience for bioanalysis. All analytes were simultaneously monitored
      in positive- and negative-ion mode by SRM (selective reaction monitoring) using
      the fast polarity switch speed of TSQ VantageTM. Method validation of the assay
      was implemented. No significant matrix effect was observed. The LLOQ of all
      analytes were <1.0ng/ml. The precision, recovery and linearity of the analysis
      met the pre-established requirements. The method was applied to the
      pharmacokinetics of ferulic acid, ligustrazine and ligustilide in Rhizoma
      Chuanxiong or Angelica sinensis extracts or monomers. 

PMID- 24140451
TI  - Immature platelet fraction in diabetes mellitus and metabolic syndrome.
AB  - INTRODUCTION: Dysregulated platelet-endothelial interaction plays a pivotal role
      in atherothrombotic events in patients with diabetes mellitus (DM). Immature
      platelet fraction (IPF) is a hematologic parameter of automated hematologic
      analyzer and is related to platelet size and cytoplasmic RNA contents. It
      reflects thrombopoiesis and also is often used as the marker of platelet
      activity. MATERIAL AND METHODS: We compared peripheral blood IPF, IPF count
      (IPC), and mean platelet volume (MPV) of DM and metabolic syndrome (MetS)
      patients with those of healthy controls. The IPF, IPC, MPV, and other blood cell
      indices were measured. RESULTS: The DM group had significantly higher IPF (2.20
      vs. 1.70%, P=.020), IPC (4.80 vs. 4.60*10(9)/L, P=.043), and MPV (10.35 vs.
      10.00fL, P=.012) than the control group. Those markers were also increased in
      MetS patients, but the differences were not statistically significant.
      Interestingly, when DM patients were stratified according to glycemic control
      status (<=6.5% HbA1c vs. 6.6-7.9% HbA1c vs. >=8% HbA1c), both IPF and IPC were
      significantly increased in poor glycemic control group (P=.014 and .003).
      Including various diabetic complications in the analysis, IPF was higher in DM
      patients complicated by cardiovascular disease than the DM group without
      cardiovascular disease. CONCLUSION: IPF is elevated in patients with diabetes and
      associated with poor glycemic control and cardiovascular complication.

PMID- 24140452
TI  - Regular ventricular pacing inhibition due to electronic artifact emitted by pulse
      generator equipped with a self-adjusting sensitivity function.

PMID- 24140453
TI  - The role of microRNA-26b in human adipocyte differentiation and proliferation.
AB  - Recent findings indicate that microRNAs (miRNAs) are involved in the regulatory
      network of adipogenesis and obesity. Thus far, only a few human miRNAs are known
      to function as adipogenic regulators, fanning interest in studies on the
      functional role of miRNAs during adipogenesis in humans. In a previous study, we
      used a microarray to assess miRNA expression during human preadipocyte
      differentiation. We found that expression of the miR-26b was increased in mature
      adipocytes. MiR-26b is an intronic miRNA located in the intron of CTDSP1 (carboxy
      terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1). Target
      prediction and Renilla luciferase analyses revealed the phosphatase and tensin
      homolog gene (PTEN) as a putative target gene. In this study, we found that miR
      26b was gradually upregulated during adipocyte differentiation. To understand the
      roles of miR-26b in adipogenesis, we adopted a loss-of-function approach to
      silence miR-26b stably in human preadipocytes. We found that miR-26b inhibition
      effectively suppressed adipocyte differentiation, as evidenced by decreased lipid
      droplets and the ability of miR-26b to decrease mRNA levels of adipocyte-specific
      molecular markers and triglyceride accumulation. Furthermore, the cell growth
      assay revealed that miR-26b inhibition promoted proliferation. Nevertheless, it
      had no effect on apoptosis. Taken together, these data indicate that miR-26b may
      be involved in adipogenesis and could be targeted for therapeutic intervention in
      obesity. 

PMID- 24140454
TI  - Leptin receptor Arg109 homozygotes display decreased total mortality as well as
      lower incidence of cardiovascular disease and related death.
AB  - Two leptin receptor single nucleotide polymorphisms, Lys109Arg and Gln223Arg,
      have been shown to associate with several risk factors for cardiovascular
      disease. In addition, we have previously shown that Arg109 and Arg223 homozygotes
      displayed lower intima-media thickness in our well-defined OPERA (Oulu Project
      Elucidating Risk of Atherosclerosis) study. This current research investigated
      the impact of these LEPR polymorphisms on cardiovascular events and related death
      as well as to total mortality in the 19-year follow-up of OPERA. Subjects were
      randomly selected, middle-aged drug-treated hypertensives and their age- and sex
      matched control subjects recruited to the OPERA study between 1990 and 1993.
      Mortality and hospital events of 1045 subjects were followed up until 2009. A
      total of 151 coronary heart disease (CHD) and 211 cardiovascular disease (CVD)
      events or deaths including 58 CHD and 69 CVD deaths occurred. Furthermore, during
      this follow-up, a total of 165 subjects died. Logistic regression analysis was
      performed to assess the impact of Lys109Arg and Gln223Arg on the events and
      death. Further modeling was performed with Cox regression for Lys109Arg. The
      logistic regression analysis revealed a significant protective impact of
      Arg109Arg genotype on CHD (OR 0.433; CI 95% 0.217-0.863) and CVD (OR 0.540; CI
      95% 0.309-0.942) events or death as well as on total mortality (OR 0.390; CI 95%
      0.196-0.775) when adjusted with age, sex and study group. Even after further
      adjustment with BMI, smoking status, systolic blood pressure and low-density
      lipoprotein cholesterol, the protective effect of Arg109Arg on CHD events or
      death and total mortality still remained statistically significant (OR 0.463; CI
      95% 0.230-0.931 and OR 0.442; CI 95% 0.218-0.896, respectively). Arg109Arg was
      also shown to confer protection against CHD mortality (HR 0.224; CI95% 0.055
      0.919) and overall mortality (HR 0.413; CI95% 0.218-0.783) also in Cox regression
      analysis. In conclusion, the Arg109Arg genotype of LEPR seems to be protective
      from cardiovascular events and death and this phenomenon seems to be independent
      of the traditional risk factors for atherosclerosis.

PMID- 24140456
TI  - Redox-mediated mechanisms and biological responses of copper-catalyzed reduction
      of the nitrite ion in vitro.
AB  - During ischemia nitrite may be converted into nitric oxide (NO) by reaction with
      heme-carrying proteins or thiol-containing enzymes. NO acts as a regulator of
      vasodilation and protector against oxidative stress-induced tissue injuries. As a
      result of ischemia-induced oxidative stress, hypoxia and/or acidosis bivalent
      copper ions (Cu(2+)) can dissociate from their physiological carrier proteins.
      Reduced by the body's own antioxidants, the resultant Cu(1+) might represent an
      effective reductant of nitrite. Here we have evaluated in vitro copper
      dissociation from copper/BSA (bovine serum albumin) complexes under ischemic
      conditions. Furthermore, using physiological concentrations, we have
      characterized the capacity of antioxidants and bivalent copper ions to serve as
      Cu(1+)-agitated catalytic sites for nitrite reduction and also the biological
      responses of this mechanism in vitro. We found that as a consequence of an acidic
      milieu and/or oxidative stress the copper-binding capacity of serum albumin
      strongly declined, leading to significant dissociation of copper ions into the
      ambient solution. At physiologically relevant pH-values Cu(2+) ions in
      combination with physiologically available copper reductants (i.e., ascorbate,
      glutathione, Fe(2+)) significantly enhanced nitrite reduction and subsequent non
      enzymatic NO generation under hypoxic but also normoxic conditions. Our data
      demonstrate for the first time that upon ischemic conditions carrier protein
      dissociated copper ions combined with appropriate reductants may serve as Cu(1+)
      driven catalytic sites for nitrite reduction, leading to the formation of
      biologically relevant NO formation. Thus, in addition to the action of heme
      proteins, copper-catalyzed non-enzymatic NO formation from nitrite might
      represent a further physiologically relevant vasodilating and NO-dependent
      protective principle to ischemic stress. 

PMID- 24140455
TI  - Strategies to Avoid Returning to Smoking (STARTS): a randomized controlled trial
      of postpartum smoking relapse prevention interventions.
AB  - The majority of women who quit smoking during pregnancy relapse postpartum and
      many experience increased depressive symptoms and concerns about body shape and
      weight. Given the relationship of weight concerns and negative mood to smoking
      relapse, interventions designed to address the postpartum experience are
      indicated. However, there are several challenges to research with postpartum
      women. We describe the rationale of a randomized controlled trial of postpartum
      smoking relapse prevention intervention and discuss methods to address the
      specific challenges to recruiting, retaining and conducting health behavior
      interventions among postpartum former smokers. Pregnant women who had quit
      smoking for at least one month prior to the 34 week of pregnancy and who were
      motivated to stay quit postpartum were recruited. Women were randomized either to
      a postpartum specific intervention designed to address concerns about mood,
      stress and weight using cognitive-behavioral techniques or to a support-only
      condition designed to control for time and attention. Intervention continues
      through six months postpartum and women complete follow-up assessments at 12-, 24
      and 52-weeks after delivery. Women (n=300) who had quit smoking as a result of
      pregnancy were recruited and are being followed. The intervention described in
      this report is designed to address stress, negative mood and concerns about
      weight that mediate smoking relapse postpartum to sustain abstinence and improve
      maternal and infant health.

PMID- 24140457
TI  - Synthesis, spectral features and biological activity of some novel hetarylazo
      dyes derived from 8-chloro-4-hydroxyl-2-quinolone.
AB  - In this study, 8-chloro-4-hydroxyl-2-quinolone was synthesized from
      cyclocondensation of corresponding dianilide and subsequently used as a potent
      coupling component with some diazotized heterocyclic amines. These compounds were
      characterized by UV-vis, FT-IR, (1)H NMR spectroscopic techniques and elemental
      analysis. Absorption spectra of these dyes were measured in six polar solvents
      and discussed with respect to the nature of solvents and substituted groups. The
      effects of acid, base, temperature and concentration on the visible absorption
      spectra of the dyes were reported. In addition, the antimicrobial activity of the
      dyes was explored in detail. 

PMID- 24140458
TI  - Brown seaweed pigment as a dye source for photoelectrochemical solar cells.
AB  - Chlorophylls based-dyes obtained from seaweeds represent attractive alternatives
      to the expensive and polluting pyridil based Ru complexes because of their
      abundance in nature. Another important characteristic is that the algae do not
      subtract either cropland or agricultural water, therefore do not conflict with
      agro-food sector. This pigment shows a typical intense absorption in the UV/blue
      (Soret band) and a less intense band in the red/near IR (Q band) spectral regions
      and for these reasons appear very promising as sensitizer dyes for DSSC. In the
      present study, we utilized chlorophylls from samples of the brown alga Undaria
      pinnatifida as sensitizer in DSSCs. The dye, extracted by frozen seaweeds and
      used without any chemical purification, showed a very good fill factor (0.69).
      Even the photelectrochemical parameters if compared with the existent literature
      are very interesting. 

PMID- 24140459
TI  - IR spectroscopic study of the HCl...O3 molecular complex in liquid argon.
AB  - Infrared spectra are reported of ozone and HCl dissolved in liquid argon (86-134
      K) at concentrations varying from 5*10(-5) to 9*10(-6) M for HCl, and from 1*10(
      3) to 5*10(-5) M for ozone. At low concentrations of O3 and of HCl, no spectral
      features due to O3-HCl complex were found. At higher concentrations (1*10(-3) of
      ozone vs 5*10(-5)-9*10(-6) of HCl), a new band near 2840 cm(-1) due to the
      HCl...O3 complex was observed. FWHM of nuHCl of the complex is 8 cm(-1). From the
      temperature dependence of the absorption band intensity, the enthalpy of the
      complex formation was estimated, DeltaH degrees =4.7+/-0.4 kJ mole(-1). The
      optimized geometry of the cis-HCl...O3 complex and a value of 6.3 kJ mole(-1) for
      its binding energy were determined by ab initio calculations.

PMID- 24140460
TI  - HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation
      to lung cancer among Chinese.
AB  - BACKGROUND: Chromosome 19q13.3 has been identified as one of the regions that
      associate with cancer risk in previous studies. METHODS: We systematically
      examined the 70.772kb region comprising four genes on chromosome 19q13.3 among
      Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform.
      The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs
      (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the
      combined effects of sixteen htSNPs provided high coverage of common haplotypes of
      ERCC2, PPP1R13L, CD3EAP and ERCC1. RESULTS: Both carriers of variant CC genotype
      [adjusted OR (95% CI)=1.28 (1.02-1.60), P=0.04] and variant C-allele among >20
      years' smokers [OR (95% CI)=2.13 (1.24-3.67), P=0.006] for CD3EAP rs735482 were
      at increased risk of lung cancer. Four haplotype blocks of strong linkage
      disequilibrium were identified. The haplotype ERCC2 rs3916874(G) and rs238415(C)
      [OR (95% CI)=1.26 (1.02-1.57), P=0.03] in block 1 and the haplotype PPP1R13L
      rs4803817(A), CD3EAP rs1046282(T), rs735482(C), ERCC1 rs3212980(A), rs3212964(G)
      [OR (95% CI)=3.56 (1.55-8.18), P=0.005] in block 3 were associated with lung
      cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the
      best significant model of two-attributes containing smoking duration and
      rs2298881 in ERCC1 (P=0.004-0.005) and suggested that the effects of high-order
      interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could
      modulate lung cancer risk. CONCLUSIONS: HapMap-based study of 19q13.3 identified
      that genetic variation of CD3EAP and two loci were associated with lung cancer
      risk and interaction of smoking duration and genetic variants was the strongest
      predictor of lung cancer risk in a Chinese population.

PMID- 24140461
TI  - Does mating prevent monogamous males from seeking other females? A study in
      prairie voles (Microtus ochrogaster).
AB  - Male prairie voles form pair bonds under laboratory conditions, but show a
      variety of mating tactics in nature. We tested them in the laboratory to
      determine if their decision to reproduce with a single or multiple females is
      related to how they process sensory information from females. Three groups of
      mated males were tested for their attentiveness toward two females and their
      odors. Males given a choice to investigate a box holding their mate or a box
      holding a sexually receptive female spent more time with the box of the sexually
      receptive female than that of their mate. Similar results were found when females
      were removed and replaced by their odors. However, males did not attend
      preferentially to the sexually receptive female under all circumstances. When
      given a choice between a sexually unreceptive and a sexually receptive female,
      males did not display a difference in their attentiveness. Furthermore, males
      tested in presence of their mate were more attentive to the odor of the sexually
      receptive female than males tested in presence of a sexually unreceptive female.
      The data suggest that access to the mate's sensory cues may influence male's
      decision to seek females other than his mate. 

PMID- 24140462
TI  - Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with
      rats.
AB  - Agmatine, decarboxylated arginine, exerts beneficial effects in various
      experimental disease models. Clinical trials indicate the safety and
      effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine
      sulfate, but longer term studies are lacking. This pilot study undertook to
      assess the safety of a longer term high dosage oral agmatine sulfate in
      laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their
      drinking water for 95 days, a regimen estimated to result in a daily dosage of
      absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and
      blood pressure were periodically measured, and general cage behavior, fur
      appearance, urination and feces appearance monitored. These parameters were also
      determined at 20 days after treatment cessation (day 115). On days 95 and 115,
      animals were euthanized for gross necropsy assessment. Agmatine-treated rats
      showed slight, but significant reductions in body weight and blood pressure, and
      reduced water consumption during treatment, which recovered completely within 20
      days after treatment cessation. Otherwise, no abnormal behaviors or organ
      pathologies were observed. These findings are first to suggest apparent safety of
      sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending
      further support to the therapeutic applications of agmatine.

PMID- 24140463
TI  - Chlorpyrifos induced toxicity in reproductive organs of female Wistar rats.
AB  - Chlorpyrifos (CPF) is an organophosphate (OP) insecticide extensively used in
      agricultural and domestic settings. Healthy adult female albino rats were divided
      into three groups of six rats in each. Two groups were dosed orally with CPF in
      vegetable oil (0.1 and 2.5 mg/kg/day) and third group was given vegetable oil for
      8 weeks. Non-significant changes were observed for body weight and feed intake. A
      disruption in estrous cyclicity was observed with a prolonged metestrous.
      Erythrocyte osmotic fragility and lipid peroxidation levels increased
      significantly. Mammary gland whole mounts revealed a significant (P<0.05-0.0001)
      increase in the ductal thickness, number of branches, alveolar and terminal end
      bud number and terminal end bud diameter. A significant increase in ovarian
      surface epithelium height, follicular diameter and follicular atresia was
      observed in treated rats (P<0.05-0.0001). A similar significant increase in the
      uterine surface epithelium height, endometrial gland epithelium height and
      myometrium thickness in higher dose group was recorded (P<0.05-0.0001). Luminal
      epithelium height and endometrial gland diameter was increased significantly in
      both the treated groups (P<0.05-0.0001). The results indicate that sub-chronic
      exposure of CPF causes oxidative stress and negative effects on the reproductive
      organs of female rats, which may be a pointer towards beginning of cancer
      incidence.

PMID- 24140464
TI  - Mechanisms involved in oxidative stress regulation.

PMID- 24140465
TI  - Polycyclic aromatic hydrocarbons in food--efflux of the conjugated biomarker 1
      hydroxypyrene is mediated by Breast Cancer Resistance Protein (ABCG2) in human
      intestinal Caco-2 cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are well-known food contaminants
      comprising compounds with carcinogenic properties. Pyrene (PYR) is an important
      non-carcinogenic PAH because its metabolites are frequently used as biomarkers to
      assess human PAH exposure. This study investigated for the first time the
      formation and transport of PYR metabolites in the human small intestinal Caco-2
      cell model using HPLC technique. The intermediate phase I metabolite 1
      hydroxypyrene formed by cytochrome P450 monooxygenases is subsequently conjugated
      by phase II enzymes to the water-soluble PYR 1-glucuronide as minor and PYR 1
      sulfate as major metabolites. The formation of the latter is mediated by human
      sulfotransferases 1A1*Arg, 1A2*1, 1A3, and 1B1. Caco-2 monolayer experiments
      revealed a predominantly apical transport of both conjugates mediated by the
      breast cancer resistance protein (BCRP/ABCG2). Additional treatment with several
      aryl hydrocarbon receptor (AhR) agonists indicate an AhR-driven induction of PYR
      metabolizing enzymes and/or ABCG2. Overall, this study provides advanced
      mechanistic insights into the bioavailability of PYR and underlines a key role of
      the human small intestinal epithelium for the first pass metabolism of
      contaminants in food.

PMID- 24140466
TI  - Modulation of liver function, antioxidant responses, insulin resistance and
      glucose transport by Oroxylum indicum stem bark in STZ induced diabetic rats.
AB  - A decoction of stem bark of Oroxylum indicum Vent. (OI) is taken (2-3 times/day)
      by the tribal people of Sikkim, India to treat diabetes but scientific validation
      of its overall potential is lacking. Present study was aimed to assess in vitro
      antihyperglycemic activity of standardized OI extract using inhibition of alpha
      glucosidase, BSA glycation and enhancement of insulin sensitivity. Antidiabetic
      and antioxidant modulatory effects of OI extract along with the blood biomarkers
      of toxic response were studied in streptozotocin (STZ) induced diabetic rats. In
      vitro analysis showed strong antioxidant capacity of OI -and potential to inhibit
      BSA glycation and alpha-glucosidase activity which was comparable to standard
      counterparts. Extract also improved insulin sensitivity in mature 3T3-L1
      adipocytes. In vivo effects of OI extract (oral 250 mg/kg b.wt.) on STZ induced
      type II diabetic rats normalized the antioxidant status (p<=0.01). Analysis of
      blood biomarkers of toxic response indicated its safety. Lowering of total
      cholesterol and HDL levels (p<=0.05) and restoration of glycated Hb (p<=0.01)
      were also found in OI treated diabetic rats. HOMA-IR, QUICKI analysis along with
      area under the curve analysis showed the capacity of OI extract to enhance the
      insulin sensitivity significantly (p<=0.01) which was confirmed by increased GLUT
      4 translocation in skeletal muscles.

PMID- 24140467
TI  - Consumption of hydrogen-rich water protects against ferric nitrilotriacetate
      induced nephrotoxicity and early tumor promotional events in rats.
AB  - The aim of this work was to test whether consumption with hydrogen-rich water
      (HW) alleviated renal injury and inhibited early tumor promotional events in
      Ferric nitrilotriacetate (Fe-NTA)-treated rats. Rats were injected with Fe-NTA
      solution (7.5mg Fe/kg body weight) intraperitoneally to induce renal injury and
      simultaneously treated with HW (1.3 +/- 0.2mg/l). We found that consumption with
      HW ameliorated Fe-NTA-induced renal injuries including suppressing elevation of
      serum creatinine and blood urea nitrogen and inhibited early tumor promotional
      events including decreasing ornithine decarboxylase activity and incorporation of
      [3H]thymidine into renal DNA. Consumption with HW suppressed Fe-NTA-induced
      oxidative stress through decreasing formation of lipid peroxidation and
      peroxynitrite and activities of NADPH oxidase and xanthine oxidase, increasing
      activity of catalase, and restoring mitochondrial function in kidneys.
      Consumption with HW suppressed Fe-NTA-induced inflammation marked by reduced NF
      kappaB, IL-6, and MCP-1 expression and macrophage accumulating in kidneys. In
      addition, consumption with HW suppressed VEGF expression, STAT3 phosphorylation
      and PCNA expression in kidneys of Fe-NTA-treated rats. Consumption with HW
      decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe
      NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced
      renal injury and inhibited early tumor promotional events in rats.

PMID- 24140468
TI  - Involvement of the mitochondrial p53 pathway in PBDE-47-induced SH-SY5Y cells
      apoptosis and its underlying activation mechanism.
AB  - 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)-elicited neurotoxicity is associated
      with neural apoptosis; however the underlying mechanisms remain unclear. To
      investigate whether the mitochondrial p53 pathway is involved in neuronal
      apoptosis induced by PBDE-47 and to correlate DNA hypomethylation with p53
      activation, human neuroblastoma (SH-SY5Y) cells were treated with different
      concentrations of PBDE-47 (1, 5, 10 MUmol/L) for 24h in vitro. The apoptosis and
      ultrastructural alterations in cells, levels of p53, Bcl-2, Bax, cytochrome c
      (Cyt c), caspase-3 and methylation status of p53 promoter were determined.
      Hoechst 33258 staining and transmission electron microscopy analysis showed that
      PBDE-47 induced SH-SY5Y cells apoptosis characterized by the typical apoptotic
      morphological changes. In addition, PBDE-47 activated the p53-dependent
      mitochondrial apoptotic pathway as evidenced by up-regulation of p53 and Bax,
      down-regulation of Bcl-2 and Bcl-2/Bax ration, enhancement of Cyt c release from
      mitochondria into the cytosol, activation of caspase-3 as well as ultrastructural
      abnormalities of mitochondria. However, no obvious decrease in p53 promoter
      methylation levels was observed in any of the treatment groups by bisulfite
      genomic sequencing. Collectively, these results suggest that the mitochondrial
      p53 pathway is involved in PBDE-47-induced SH-SY5Y cells apoptosis, nevertheless
      p53 promoter hypomethylation may not be implicated in this process.

PMID- 24140469
TI  - Hepatoprotective effect of mulberry water extracts on ethanol-induced liver
      injury via anti-inflammation and inhibition of lipogenesis in C57BL/6J mice.
AB  - Many plant extracts and their bioactive substances are well recognized for their
      potential to exert as chemoprotective agents against common alcoholic liver
      injury. In this study, the effects of Mulberry water extracts (MWE) treatment in
      the prevention of alcohol-induced liver injury were investigated in mice. MWE
      contain many nutrients and bioactive substances, including fifteen types of
      polyphenols and anthocyanin compounds. The parameters of histopathology,
      immunohistochemistry, antioxidant defense and proinflammatory mediator
      demonstrated the inhibitory effect of MWE on alcohol-induced liver injury. Plasma
      and hepatic content analysis showed that MWE inhibited the levels of liver injury
      biomarkers (AST, ALT and ALP), triglyceride (TG) and cholesterol (TC).
      Furthermore, treatment with MWE lessened the expression of lipid synthesis
      related proteins, increased the p-AMPK/AMPK ratio and PPAR-alpha. Fatty acid
      oxidation and export via microsomal triglyceride transfer protein (MTP) were both
      activated as well as carnitine palmitoyltransferase-1 (CPT1). These results
      suggested that MWE prevents alcohol-induced liver injury through the activation
      of the AMPK and PPAR-alpha signal. This may be mediated by multiple pathways,
      including reduced lipid accumulation and lipid synthesis, increased fatty acid
      transport and fatty acid oxidation responses, decreased oxidative stress and
      facilitated anti-inflammation. 

PMID- 24140470
TI  - Evaluation of subchronic toxicity of GRD081, a dual PI3K/mTOR inhibitor, after 28
      day repeated oral administration in Sprague-Dawley rats and beagle dogs.
AB  - GRD081, a newly developed dual PI3K/mTOR inhibitor, is now being considered for
      evaluation in phase I clinical trial. In this work, the subchronic toxicity of
      GRD081 in Sprague-Dawley (SD) rats and beagle dogs has been characterized. Rats
      and dogs received GRD081 orally (2, 5, 10 and 1, 2, 4 mg/kg/day, respectively) on
      a consecutive daily dosing schedule for 28 days following a 14 days of recovery
      period. The treatment resulted in unscheduled mortality in rats receiving 5
      mg/kg/day and 10 mg/kg/day. The adverse effects of GRD081 on rats and dogs mainly
      included myelosuppression, immunosuppression, hematological toxicity, and
      moderate liver, pancreas and kidney toxicity. These observations are consistent
      with pharmacologic perturbations of physiologic processes associated with the
      intended molecular targets for this class of PI3K/mTOR signaling inhibitors. Most
      of the treatment-induced effects were reversible upon discontinuation of
      treatment. The no-observed-adverse-effect level (NOAEL) of GRD081 was 1mg/kg/day
      for beagle dogs and less than 2 mg/kg/day for SD rats.

PMID- 24140471
TI  - Ouabain induces endocytosis and degradation of tight junction proteins through
      ERK1/2-dependent pathways.
AB  - In addition to being a very well-known ion pump, Na(+), K(+)-ATPase is a cell
      cell adhesion molecule and the receptor of digitalis, which transduces regulatory
      signals for cell adhesion, growth, apoptosis, motility and differentiation.
      Prolonged ouabain (OUA) blockage of activity of Na(+), K(+)-ATPase leads to cell
      detachment from one another and from substrates. Here, we investigated the
      cellular mechanisms involved in tight junction (TJ) disassembly upon exposure to
      toxic levels of OUA (>=300 nM) in epithelial renal canine cells (MDCK). OUA
      induces a progressive decrease in the transepithelial electrical resistance
      (TER); inhibitors of the epidermal growth factor receptor (EGFR, PD153035), cSrc
      (SU6656 and PP2) and ERK1/2 kinases (PD98059) delay this decrease. We have
      determined that the TER decrease depends upon internalization and degradation of
      the TJs proteins claudin (CLDN) 2, CLDN-4, occludin (OCLN) and zonula occludens-1
      (ZO-1). OUA-induced degradation of proteins is either sensitive (CLDN-4, OCLN and
      ZO-1) or insensitive (CLDN-2) to ERK1/2 inhibition. In agreement with the protein
      degradation findings, OUA decreases the cellular content of ZO-1 and CLDN-2 mRNAs
      but surprisingly, increases the mRNA of CLDN-4 and OCLN. Changes in the mRNA
      levels are sensitive (CLDN-4, OCLN and ZO-1) or insensitive (CLDN-2) to ERK1/2
      inhibition as well. Thus, toxic levels of OUA activate the EGFR-cSrc-ERK1/2
      pathway to induce endocytosis, internalization and degradation of TJ proteins. We
      also observed decreases in the levels of CLDN-2 protein and mRNA, which were
      independent of the EGFR-cSrc-ERK1/2 pathway.

PMID- 24140472
TI  - Yolk hydrolases in the eggs of Anticarsia gemmatalis hubner (Lepidoptera:
      Noctuidae): a role for inorganic polyphosphate towards yolk mobilization.
AB  - Despite being the main insect pest on soybean crops in the Americas, very few
      studies have approached the general biology of the lepidopteran Anticarsia
      gemmatalis and there is a paucity of studies with embryo formation and yolk
      mobilization in this species. In the present work, we identified an acid
      phosphatase activity in the eggs of A. gemmatalis (agAP) that we further
      characterized by means of biochemistry and cell biology experiments. By testing
      several candidate substrates, this enzyme proved chiefly active with
      phosphotyrosine; in vitro assays suggested a link between agAP activity and
      dephosphorylation of egg yolk phosphotyrosine. We also detected strong activity
      with endogenous and exogenous short chain polyphosphates (PolyP), which are
      polymers of phosphate residues involved in a number of physiological processes.
      Both agAP activity and PolyP were shown to initially concentrate in small
      vesicles clearly distinct from typically larger yolk granules, suggesting
      subcellular compartmentalization. As PolyP has been implicated in inhibition of
      yolk proteases, we performed in vitro enzymatic assays with a cysteine protease
      to test whether it would be inhibited by PolyP. This cysteine protease is
      prominent in Anticarsia egg homogenates. Accordingly, short chain PolyP was a
      potent inhibitor of cysteine protease. We thereby suggest that PolyP hydrolysis
      by agAP is a triggering mechanism of yolk mobilization in A. gemmatalis. 

PMID- 24140473
TI  - Viral evolution explains the associations among hepatitis C virus genotype,
      clinical outcomes, and human genetic variation.
AB  - Specific human polymorphisms, most commonly found in Central Africa, can predict
      the success of drug treatment against the hepatitis C virus (HCV), a significant
      and globally-distributed human pathogen. However, this association is only found
      for a subset of HCV genotypes. Despite receiving considerable attention in the
      medical and virological literature, no evolutionary explanation for this curious
      pattern has been put forward. Here we suggest that the 'drug treatment
      resistance' phenotype exhibited today by some HCV genotypes evolved hundreds to
      thousands of years ago in response to human genetic variation local to Central
      Africa: an adaptation that has since accrued a new function in the era of anti
      viral drug treatment. This could represent one of the oldest known examples of
      viral exaptation at the population level. 

PMID- 24140474
TI  - Genotype analysis of hepatitis E virus from sporadic hepatitis E cases in
      northern China.
AB  - Hepatitis E is an important public health problem in many countries. However,
      there is no definite conclusion about the zoonotic reservoir, transmission
      patterns and risk factors of hepatitis E in the human population. The aim of this
      study was to analyze the epidemiological and viral genotype characteristics of
      hepatitis E cases in northern China. Surveillance was conducted in two hospitals
      in Liaoning and Hebei province from July 2010 to June 2012. Out of a total of 116
      diagnosed patients, 88 (75.9%) were male and 28 (24.1%) were female and most
      (73%) were in the age group 40-70 years. In both hospitals, cases were diagnosed
      more frequently in March than in other months. HEV RNA was amplified from 41
      patients and characterized by nucleotide sequencing and phylogenetic analysis.
      Most of the isolates (37 strains, 90.3%) were genotype 4, including subgenotypes
      4a, 4b, 4d, 4h, 4i and a new subgenotype. One subgenotype 3a strain was isolated
      from Baoding, Hebei province. Three genotype 1b strains were found from patients
      in Jinzhou, Liaoning province. Most of the genotype 4 strains and the genotype 3
      strains were phylogenetically related to known swine isolates. In conclusion, the
      finding that HEV infects mostly middle-aged and elderly men and that the
      incidence spiked in March may reflect the zoonotic transmission characteristics
      of HEV infection. Pigs, but not rabbits, were the important reservoirs in this
      area, because genotype 4 HEV was found to be responsible for the majority
      hepatitis E cases. However, genotype 1 is still present in northern China. Also,
      the first isolation of genotype 3 HEV in this area indicates that alternative
      routes of HEV transmission might exist.

PMID- 24140475
TI  - New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis:
      targeted therapy of gamma-secretase inhibitor resistant T-cell acute
      lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is characterized as a high-risk
      stratified disease associated with frequent relapse, chemotherapy resistance, and
      a poorer prognostic outlook than B-precursor ALL. Many of the challenges in
      treating T-ALL reflect the lack of prognostic cytogenetic or molecular
      abnormalities on which to base therapy, including targeted therapy. Notch1
      activating mutations were identified in more than 50% of T-ALL cases and can be
      therapeutically targeted with gamma-secretase inhibitors (GSIs). Mutant Notch1
      can activate cMyc and PI3K-AKT-mTOR1 signaling in T-ALL. In T-ALLs with wild-type
      phosphatase and tensin homolog deleted on chromosome ten (PTEN), Notch1
      transcriptionally represses PTEN, an effect reversible by GSIs. Notch1 also
      promotes growth factor receptor (IGF1R and IL7Ralpha) signaling to PI3K-AKT. Loss
      of PTEN is common in primary T-ALLs due to mutation or posttranslational
      inactivation and results in chronic activation of PI3K-AKT-mTOR1 signaling, GSI
      resistance, and repression of p53-mediated apoptosis. Notch1 itself might
      regulate posttranslational inactivation of PTEN. PP2A is activated by Notch1 in
      PTEN-null T-ALL cells, and GSIs reduce PP2A activity and increase phosphorylation
      of AKT, AMPK, and p70S6K. This review focuses on the central role of the PI3K-AKT
      mTOR1 signaling in T-ALL, including its regulation by Notch1 and potential
      therapeutic interventions, with emphasis on GSI-resistant T-ALL. 

PMID- 24140476
TI  - Genetic variations in IL6 and IL12B decreasing the risk for psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disorder. Recent studies
      associated a number of genetic variants to this immune-mediated pathology.
      OBJECTIVE: This study aims to assess whether the association between the non
      susceptibility allelic variants of IL12B single-nucleotide polymorphism (SNPs)
      rs3212227 and rs6887695, IL23R SNPs rs11209026 and rs7530511, IL6 SNP rs1800795
      and HLA-Cw6 could be correlated with decreased risk for psoriasis. MATERIAL AND
      METHODS: We genotyped 67 psoriasis patients and 69 healthy subjects for
      polymorphisms of IL12B rs3212227 and rs6887695, IL23R rs11209026 and rs7530511,
      IL6 rs1800795 and for the presence of HLA-Cw6. The patients and controls were
      recruited from Dermatology Department, part of "Tor Vergata" Clinic, Rome.
      Demographic data of the control group matched those of psoriasis patients, with a
      female:male ratio of 2.55 and mean age of 45.5+/-12.2 years for patients and
      44.8+/-11.7 years for controls. RESULTS: The following genotypes were less
      frequent in patients: IL12B SNP rs6887695 CC (OR, 0.179; CI95% 0.046-0.699;
      p=0.01), IL6 SNP rs1800795 CG (OR, 0.367; CI95% 0.179-0.753; p=0.006) and IL6 SNP
      rs1800795 CC (OR, 0.069; CI95% 0.008-0.586; p=0.01). Also the HLA-Cw6 allele was
      rarely found in controls (OR, 0.459; CI95% 0.230-0.916; p=0.02). The multivariate
      analysis showed that the existence of at least one C allele in both IL12B SNP
      rs6887695 and IL6 SNP rs1800795 or the absence of HLA-Cw6 allele and at least one
      C allele in IL12B SNP rs6887695 or IL6 SNP rs1800795 is associated with a lower
      risk of psoriasis (OR, 0.185; CI95% 0.037-0.929; p=0.04). The presence of at
      least one C allele in both IL12B SNP rs6887695 and IL6 SNP rs1800795 and the
      absence of HLA-Cw6 allele decreased even further the risk of psoriasis (OR,
      0.038; CI95% 0.006-0.244; p=0.001). CONCLUSION: We report carriers of variations
      in the IL6, IL12B and absence of HLA-Cw6 as having decreased risk for psoriasis.

PMID- 24140477
TI  - Cell-to-cell spread of HIV-1 and evasion of neutralizing antibodies.
AB  - Cell-to-cell spread of human immunodeficiency virus (HIV-1) between immune cells
      was first observed over 20 years ago. During this time, the question of whether
      this infection route favours viral evasion of neutralizing antibodies (NAbs)
      targeting the virus envelope glycoprotein (Env) has been repeatedly investigated,
      but with conflicting results. A clearer picture has formed in the last few years
      as more broadly neutralizing antibodies have been isolated and we gain further
      insight into the mechanisms of HIV-1 transmission at virological and infectious
      synapses. Nevertheless consensus is still lacking, a situation which may be at
      least partly explained by variability in the experimental approaches used to
      study the activity of NAbs in the cell-to-cell context. In this review we focus
      on the most critical question concerning the activity of NAbs against cell-to
      cell transmission: is NAb inhibition of cell-to-cell HIV-1 quantitatively or
      qualitatively different from cell-free infection? Overall, data consistently show
      that NAbs are capable of blocking HIV-1 infection at synapses, supporting the
      concept that cell-to-cell infection occurs through directed transfer of virions
      accessible to the external environment. However, more recent findings suggest
      that higher concentrations of certain NAbs might be needed to inhibit synaptic
      infection, with important potential implications for prophylactic vaccine
      development. We discuss several mechanistic explanations for this relative and
      selective loss of activity, and highlight gaps in knowledge that are still to be
      explored. 

PMID- 24140478
TI  - RATS: Rapid Automatic Tissue Segmentation in rodent brain MRI.
AB  - BACKGROUND: High-field MRI is a popular technique for the study of rodent brains.
      These datasets, while similar to human brain MRI in many aspects, present unique
      image processing challenges. We address a very common preprocessing step, skull
      stripping, which refers to the segmentation of the brain tissue from the image
      for further processing. While several methods exist for addressing this problem,
      they are computationally expensive and often require interactive post-processing
      by an expert to clean up poorly segmented areas. This further increases total
      processing time per subject. NEW METHOD: We propose a novel algorithm, based on
      grayscale mathematical morphology and LOGISMOS-based graph segmentation, which is
      rapid, robust and highly accurate. RESULTS: Comparative results obtained on two
      challenging in vivo datasets, consisting of 22 T1-weighted rat brain images and
      10 T2-weighted mouse brain images illustrate the robustness and excellent
      performance of the proposed algorithm, in a fraction of the computational time
      needed by existing algorithms. COMPARISON WITH EXISTING METHODS: In comparison to
      current state-of-the-art methods, our approach achieved average Dice similarity
      coefficient of 0.92 +/- 0.02 and average Hausdorff distance of 13.6 +/- 5.2
      voxels (vs. 0.85 +/- 0.20, p<0.05 and 42.6 +/- 22.9, p << 0.001) for the rat
      dataset, and 0.96 +/- 0.01 and average Hausdorff distance of 21.6 +/- 12.7 voxels
      (vs. 0.93 +/- 0.01, p <<0.001 and 33.7 +/- 3.5, p <<0.001) for the mouse dataset.
      The proposed algorithm took approximately 90s per subject, compared to 10-20 min
      for the neural-network based method and 30-90 min for the atlas-based method.
      CONCLUSIONS: RATS is a robust and computationally efficient method for accurate
      rodent brain skull-stripping even in challenging data.

PMID- 24140479
TI  - Impact of endothelial nitric oxide synthase gene polymorphism on severity of
      enterovirus 71-infection in Chinese children.
AB  - OBJECTIVES: Genetic polymorphism G894T on the endothelial nitric oxide synthase
      (eNOS) gene has been reported as a susceptibility factor in a number of diseases,
      but evidence of its effect on enterovirus 71 (EV71) infection is lacking. This
      study investigated the possible association between this polymorphism (rs1799983)
      and disease severity in Chinese children with EV71 infection. DESIGN AND METHODS:
      185 children with EV71 infection (83 with severe and 102 with mild disease) and
      234 control healthy children underwent testing with polymerase chain reaction
      restriction fragment length polymorphism (PCR-RLFP) to detect G894T polymorphism.
      In addition, plasma levels of nitric oxide (NO), interleukin 1 beta (IL-1beta),
      interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) and serum eNOS
      activity were measured according to genotype. RESULTS: The presence of GT+TT
      genotypes and T allele were associated with severe cases compared to genotype GG
      (OR 2.5, 95% CI 1.2-5.3, P=0.017) and G (OR 2.4, 95% CI 1.2-4.8, P=0.011).
      Furthermore, in EV71 encephalitis, GT+TT genotype and T allele were also more
      frequent than GG and G (P<0.05). The NO level and eNOS activity in T carriers
      (GT+TT) (84.3+/-2.5MUmol/L and 14.4+/-1.8U/mL) were significantly less compared
      to in G carriers (GG) (92.0+/-1.5MUmol/L and 19.1+/-1.7U/mL, P<0.001). But T
      carriers had higher plasma levels of IL-1beta, IL-6, and TNF-alpha than people
      without a T allele (P<0.001), and a significant negative correlation was observed
      between NO and cytokine levels. CONCLUSION: The results indicate that carrying
      the T allele of the eNOS G894T gene polymorphism was associated with EV71
      infection, and could be a susceptibility factor in the development of EV71
      infection in Chinese children.

PMID- 24140480
TI  - Perinatal mental illness: definition, description and aetiology.
AB  - Perinatal mental illness is a significant complication of pregnancy and the
      postpartum period. These disorders include depression, anxiety disorders, and
      postpartum psychosis, which usually manifests as bipolar disorder. Perinatal
      depression and anxiety are common, with prevalence rates for major and minor
      depression up to almost 20% during pregnancy and the first 3 months postpartum.
      Postpartum blues are a common but lesser manifestation of postpartum affective
      disturbance. Perinatal psychiatric disorders impair a woman's function and are
      associated with suboptimal development of her offspring. Risk factors include
      past history of depression, anxiety, or bipolar disorder, as well psychosocial
      factors, such as ongoing conflict with the partner, poor social support, and
      ongoing stressful life events. Early symptoms of depression, anxiety, and mania
      can be detected through screening in pregnancy and the postpartum period. Early
      detection and effective management of perinatal psychiatric disorders are
      critical for the welfare of women and their offspring. 

PMID- 24140481
TI  - Reuse of grits waste for the production of soil--cement bricks.
AB  - This investigation focuses on the reuse of grits waste as a raw material for
      replacing Portland cement by up to 30 wt.% in soil-cement bricks. The grits waste
      was obtained from a cellulose factory located in south-eastern Brazil. We
      initially characterized the waste sample with respect to its chemical
      composition, X-ray diffraction, fineness index, morphology, pozzolanic activity,
      and pollution potential. Soil-cement bricks were then prepared using the waste
      material and were tested to determine their technological properties (e.g., water
      absorption, apparent density, volumetric shrinkage, and compressive strength).
      Microstructural evolution was accompanied by confocal microscopy. It was found
      that the grits waste is mainly composed of calcite (CaCO3) particles. Our results
      indicate that grits waste can be used economically, safely, and sustainably at
      weight percentages of up to 20% to partially replace Portland cement in soil
      cement bricks. 

PMID- 24140482
TI  - Quantifying benefits of resource recovery from sanitation provision in a
      developing world setting.
AB  - Despite concerns of sanitation provision, water scarcity, climate change, and
      resource depletion, limited research has been conducted to assess the
      environmental impact of wastewater treatment and resource recovery strategies to
      improve access to sanitation and resource utilization in developing world
      settings. Accordingly, the goal of this study is to evaluate the potential
      benefits of mitigating the environmental impact of two small community-managed
      wastewater treatment systems in rural Bolivia using resource recovery (i.e.,
      water reuse and energy recovery). Life Cycle Assessment (LCA) is used to estimate
      the embodied energy, carbon footprint, and eutrophication potential of these
      systems under existing and resource recovery conditions. Two distinct
      technologies are analyzed: (1) an upflow anaerobic sludge blanket reactor (UASB)
      followed by two maturation ponds in series (UASB-Pond system) and (2) a
      facultative pond followed by two maturation ponds in series (3-Pond system). For
      the existing systems, bathroom and collection infrastructure had a higher energy
      intensity than the treatment processes, whereas direct methane emissions from
      treatment were the primary contributors to the carbon footprint. Taking advantage
      of reclaimed water was found to greatly reduce the eutrophication potential for
      both systems, in which the reduction increases proportionally to the percentage
      of water that is reclaimed. Energy recovery from the UASB-Pond system provided a
      19% reduction in embodied energy and a 57% reduction in carbon footprint.
      Combining water reuse and energy recovery for the UASB-Pond system reduced the
      eutrophication potential, embodied energy and carbon footprint simultaneously.
      This highlights the benefits of integrated resource recovery. 

PMID- 24140483
TI  - Tetracycline removal from water by adsorption/bioadsorption on activated carbons
      and sludge-derived adsorbents.
AB  - The objective of this study was to analyze the behavior of activated carbons with
      different chemical and textural natures in the adsorption of three tetracyclines
      (TCs) (tetracycline, oxytetracycline, and chlortetracycline). We also assessed
      the influence of the solution pH and ionic strength on the adsorption of these
      compounds and studied their removal by the combined use of microorganisms and
      activated carbon (bioadsorption). Sludge-derived materials were also used to
      remove TC from water. The capacity of these materials to adsorb TC was very high
      and was much greater than that of commercial activated carbon. This elevated
      adsorption capacity (512.1-672.0 mg/g) is explained by the high tendency of TC to
      form complex ions with some of the metal ions present in these materials. The
      medium pH and presence of electrolytes considerably affected TCs adsorption on
      commercial activated carbon. These results indicate that electrostatic adsorbent
      adsorbate interactions play an important role in TC adsorption processes when
      conducted at pH values that produce TC deprotonation. The presence of bacteria
      during the TCs adsorption process decreases their adsorption/bioadsorption on the
      commercial activated carbon, weakening interactions between the adsorbate and the
      microfilm formed on the carbon surface. The adsorptive capacity was considerably
      lower in dynamic versus static regime, attributable to problems of TC diffusion
      into carbon pores and the shorter contact time between adsorbate and adsorbent. 

PMID- 24140484
TI  - Sonochemical degradation of the persistent pharmaceutical carbamazepine.
AB  - The objective of this work was to evaluate the potential of a sonochemical
      oxidation process for the degradation of carbamazepine (CBZ). Several factors,
      such as electrical power, treatment time, pH and initial concentration of CBZ
      were investigated. Using a 2(4) factorial matrix, the best performance for CBZ
      degradation (90.1% of removal) was obtained with an electrical power of 40 W, a
      treatment time of 120 min and an initial pH of 10.0 imposed in the presence of
      6.0 mg L(-1) of CBZ. The treatment time and the calorimetric power were the most
      influential parameters on the degradation rate of CBZ. Subsequently, the optimal
      experimental parameters for CBZ degradation were investigated using central
      composite design. The sonochemical oxidation process, applied under optimal
      operating conditions (at an electrical power of 43 W for 116 min), oxidized 86
      and 90% of the initial CBZ concentration of 5.62 mg L(-1) and 8.05 MUg L(-1),
      respectively. During the sonochemical process, CBZ was primarily transformed into
      anthranilic acid and acridine. 

PMID- 24140485
TI  - Cost-effective mitigation of greenhouse gas emissions from different dairy
      systems in the Waikato region of New Zealand.
AB  - The New Zealand dairy industry produces approximately 17% of this country's total
      greenhouse gas emissions (GHG-e) and it is also this nation's largest export
      industry. The industry needs to reduce GHG-e under proposed policy directives and
      for ongoing market security. Given these pressures, there is the need to identify
      cost-effective management strategies to reduce on-farm GHG-e. The objective of
      this study was to investigate how the management of dairy farms in the Waikato
      region of New Zealand could change to minimise the abatement costs associated
      with GHG-e mitigation. Three typical farm systems importing low (less than 10%),
      medium (10-20%), and high (more than 20%) amounts of supplement are modelled
      using a non-linear optimisation model. A reduction in nitrogen fertiliser
      application was the production factor that changed the most to achieve the cap in
      all of the simulated systems, followed by a reduction in stocking rate. With the
      prices used in this study, decreasing farming intensity by reducing nitrogen
      fertiliser by 21-42% and stocking rate by 8-10% represented a cost of $68-$119/ha
      and a production reduction of 54-117 kg MS/ha for the three systems studied.
      Improving reproductive performance proved to be effective in reducing GHG-e,
      allowing for fewer replacement cows to be supported. However, it did not have a
      significant effect on profit when emissions were unconstrained. Nitrification
      inhibitors and stand-off pads were not identified as useful mitigation options,
      given their high cost relative to de-intensification. 

PMID- 24140486
TI  - Potentials and limitations of biomethane and phosphorus recovery from sludges of
      brackish/marine aquaculture recirculation systems: a review.
AB  - Brackish/marine recirculation aquaculture systems (RAS) produce a relatively
      small but concentrated waste stream. The produced waste is perceived as a
      constraint for sustainable development of brackish/marine RAS. Appropriate
      disposal of sludge or waste from brackish/marine RAS is of great importance for
      widespread acceptance and implementation. Anaerobic stabilization of RAS sludge
      is considered as a potential cost-effective methodology to achieve effective
      sludge reduction and biogas production. Therefore, this review presents an
      overview of studies conducted on anaerobic digestion of sludge from
      brackish/marine RAS. Several researchers have shown that specific methane yield
      (SMY) of anaerobic digestion of sludges from brackish/marine RAS is relatively
      low, mainly in the range of 0.001-0.184 m(3) CH4 (STP)/kg COD of sludge added.
      The possible reasons for low SMY are reviewed in this work and can be mainly
      attributed to applied experimental set-ups, particularly improper inoculum, and
      high salinity, mainly resulting from high sodium cation levels. This review also
      evaluates the potentials and limitations for phosphorus recovery from the waste
      streams. Additionally, corresponding approaches to enhance specific methanogenic
      activities are proposed, particularly about the need for further thickening
      sludges from brackish/marine RAS in order to increase SMY from the wastes and
      downsize the anaerobic digestion units. 

PMID- 24140487
TI  - Imidacloprid induces changes in the structure, genetic diversity and catabolic
      activity of soil microbial communities.
AB  - This is the first report describing the effect of imidacloprid applied at field
      rate (FR, 1 mg/kg of soil) and 10 times the FR (10*FR, 10 mg/kg of soil) on the
      structural, genetic and physiological diversity of soil bacterial community as
      determined by the phospholipid fatty acid (PLFA), the denaturing gradient gel
      electrophoresis (DGGE), and the community level physiological profile (CLPP)
      approaches. PLFA profiles showed that imidacloprid significantly shifted the
      microbial community structure and decreased the biomass of the total, bacterial
      and fungal PLFAs, however, this effect was transient at the FR dosage. The
      alterations in DGGE patterns caused by imidacloprid application, confirmed
      considerable changes in the overall richness and diversity of dominant bacteria.
      Although, as a result of imidacloprid application, the metabolic activity of
      microbial communities was generally lower, the richness and functional
      biodiversity of the soil microbial community were not negatively affected. In
      general, the analysis of the variance indicated that the measured parameters were
      significantly affected by treatment and the incubation time, however, the
      incubation time effect explained most of the observed variance. Imidacloprid
      degradation and the appearance of some new bands in DGGE profiles suggest the
      evolution of bacteria capable of degrading imidacloprid among indigenous
      microflora. 

PMID- 24140488
TI  - Development of adrenergic and cholinergic receptor cardiovascular regulatory
      capacity in the Canada goose (Branta canadensis) and domestic goose (Anser anser
      domesticus).
AB  - Adrenergic control of cardiovascular function is a common component of regulation
      in embryonic birds studied to date. Our goal was to investigate adrenergic and
      cholinergic cardiovascular regulation in two goose species, the Canada goose
      (Branta canadensis) and the related domestic goose (Anser anser domesticus) to
      determine if these species possess similar regulation during embryonic
      development. We determined mean arterial pressure (Pm) and heart rate (fH)
      responses to serial blockade of cholinergic, beta-adrenergic and alpha-adrenergic
      receptors in B. canadensis and A. domesticus at 70 and 90% of total incubation
      (28days). Both species possessed cholinergic and beta-adrenergic tone on fH at
      70% of incubation that increased in intensity with development. In addition, a
      constant alpha-adrenergic tone on Pm was present in both species. Our findings
      indicate that these geese species possess both cholinergic and adrenergic
      cardiovascular regulation providing information needed for speculation regarding
      the commonalities in the ontogeny of these cardiovascular regulatory elements in
      birds. 

PMID- 24140489
TI  - Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility
      to ischemic stroke: a meta-analysis.
AB  - Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T
      polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007;
      Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are
      inconsistent. To investigate the possible associations between the MTHFR gene
      polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case
      control studies associated with MTHFR gene C667T involving 2223 cases and 2936
      controls were included. Heterogeneity among studies was evaluated with I(2) and
      Egger's test and an inverted funnel plot was used to assess publication bias.
      Odds ratio (OR) was observed to identify the associations. Statistically
      significant association with ischemic stroke was identified for allele T
      polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI):
      1.17-1.40, P<0.00001] and marginally significant association was detected with
      genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and
      genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The
      results suggested that the MTHFR C667T genetic polymorphism was significantly
      associated with increased risk of ischemic stroke.

PMID- 24140490
TI  - Intragenic DNA methylation status down-regulates bovine IGF2 gene expression in
      different developmental stages.
AB  - DNA methylation is a key epigenetic modification in mammals and has an essential
      and important role in muscle development. Insulin-like growth factor 2 (IGF2) is
      a fetal growth and differentiation factor that plays an important role in muscle
      growth and in myoblast proliferation and differentiation. The aim of this study
      was to evaluate the expression of IGF2 and the methylation pattern on the
      differentially methylated region (DMR) of the last exon of IGF2 in six tissues
      with two different developmental stages. The DNA methylation pattern was compared
      using bisulfite sequencing polymerase chain reaction (BSP) and combined bisulfite
      restriction analysis (COBRA). The quantitative real-time PCR (qPCR) analysis
      indicated that IGF2 has a broad tissue distribution and the adult bovine group
      showed significant lower mRNA expression levels than that in the fetal bovine
      group (P<0.05 or P<0.01). Moreover, the DNA methylation level analysis showed
      that the adult bovine group exhibited a significantly higher DNA methylation
      levels than that in the fetal bovine group (P<0.05 or P<0.01). These results
      indicate that IGF2 expression levels were negatively associated with the
      methylation status of the IGF2 DMR during the two developmental stages. Our
      results suggest that the methylation pattern in this DMR may be a useful
      parameter to investigate as a marker-assisted selection for muscle developmental
      in beef cattle breeding program and as a model for studies in other species. 

PMID- 24140491
TI  - Genetic insight of schizophrenia: past and future perspectives.
AB  - Schizophrenia (SCZ) has a heritability of about 80%, and the search for the
      genetic basis of this disease has been frustrating. Because schizophrenia has no
      distinguishing pathology or diagnostic criteria, it is difficult to relate gene
      changes to discrete physiological or biochemical changes associated with the
      disease. Schizophrenia fits the profile of a complex disorder in which multiple
      genes interact along with environmental influences to produce a range of
      phenotypes. There is accumulating evidence that both common genetic variants with
      small effects and rare genetic lesions with large effects determine risk of SCZ.
      As recently shown, thousands of common single nucleotide polymorphisms (SNPs),
      each with small effect, cumulatively could explain about 30% of the underlying
      genetic risk of SCZ. The ability of positional genetics to implicate novel genes
      and pathways will open up new vistas for neurobiological research, and all the
      signs are that genetic research is poised to deliver crucial insights into the
      nature of schizophrenia. In this review, we outline a general theoretical
      background of genetic mechanisms involved in SCZ. 

PMID- 24140492
TI  - Novel alpha-galactosidase A mutation in patients with severe cardiac
      manifestations of Fabry disease.
AB  - Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or
      total inactivation of alpha-galactosidase A (alpha-gal A), a lysosomal hydrolase.
      This inactivation is responsible for the accumulation of undegraded
      glycosphingolipids in the lysosomes with subsequent cellular and microvascular
      dysfunction. Fabry is considered a rare disease, with an incidence of 1:40,000;
      however, there are good reasons to believe that it is often seen but rarely
      diagnosed. To date, more than 600 mutations have been identified in human GLA
      gene that are responsible for FD. We describe the case of a 54-year-old male
      patient, who presented with left ventricular hypertrophy, chronic renal failure
      and acroparaesthesias, which are considered to be specific features of FD.
      Clinical and instrumental investigations showed several cardiovascular
      manifestations. The molecular analysis of GLA gene revealed a novel mutation in
      the fifth exon, called N249K, and the enzymatic analysis showed no alpha
      galactosidase A activity. Family screening detected the same mutation in some
      relatives and also the enzymatic analysis confirmed the diagnosis of FD. In
      conclusion, these data suggest that the N249K mutation may be associated with
      cardiac manifestations of FD combined with other classical features of the
      disease. 

PMID- 24140493
TI  - The polymorphism (-600 C>A) of CpG methylation site at the promoter region of
      CYP17A1 and its association of male infertility and testosterone levels.
AB  - Cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1) is a key
      regulatory enzyme in the steroidogenic pathway. The functional and clinical
      relevance of novel CYP17A1 promoter single nucleotide polymorphism (-600 C>A,
      rs17115149) was investigated with male infertility. Case-control association
      study of CYP17A1 from 456 infertile men performed with 465 normal fertile men.
      The rs17115149 at the promoter region of CYP17A1 was significantly associated
      with Oligoasthenoteratozoospermia (OAT, P=0.0015, n=265). 5-aza-dC treatment to B
      lymphocyte cells increased the CYP17A1 expression. Direct bisulfite sequencing of
      five human tissues showed that the rs17115149 is located at -600bp (-600C>A)
      before transcription start site within the CpG islands of CYP17A1 promoter. This 
      600 Cytosine of CpG site was highly methylated in colon and stomach tissues, but
      low methylated in adrenal gland, kidney and testis with higher CYP17A1 RNA
      expression. Especially, this polymorphism is statistically significant associated
      with testosterone levels from infertile males (n=197, P<0.05). CYP17A1 promoter
      polymorphism (rs17115149, -600C>A) is a functional regulatory SNP which
      associated with its expression possibly by epigenetic pathway, which may signify
      a genetic risk factor for male infertility. 

PMID- 24140494
TI  - Association of the rs6235 variant in the proprotein convertase subtilisin/kexin
      type 1 (PCSK1) gene with obesity and related traits in a Taiwanese population.
AB  - One particularly interesting single nucleotide polymorphism (SNP), rs6235
      (encoding an S690T substitution), in the proprotein convertase subtilisin/kexin
      type 1 (PCSK1) gene has been widely associated with obesity in several European
      cohorts. The present study was intended to investigate the association between
      the PCSK1 rs6235 SNP and the prevalence of overweight or obesity, or obesity
      related metabolic traits in a Taiwanese population. A total of 964 Taiwanese
      subjects with general health examinations were analyzed. Our data revealed no
      association of PCSK1 rs6235 with the risk of obesity or overweight in the
      complete subjects. However, the PCSK1 rs6235 SNP exhibited a significant
      association with overweight among the male subjects (P=0.03), but not among the
      female subjects. Furthermore, the carriers of GG variant had a significantly
      higher waist circumference than those with the CC variant (82.5 +/- 11.5 vs. 81.2
      +/- 10.2 cm; P=0.01) and those with the CG variant (82.5 +/- 11.5 vs. 81.4 +/-
      10.4 cm; P=0.021). In addition, the carriers of GG variant had a higher diastolic
      blood pressure than those with the CC variant (81.9 +/- 14.2 vs. 80.3 +/- 12.9 mm
      Hg; P=0.023). Our study indicates that the PCSK1 rs6235 SNP may contribute to the
      risk of overweight in men and predict obesity-related metabolic traits such as
      waist circumference and diastolic blood pressure in Taiwanese subjects.

PMID- 24140495
TI  - Dynamic expression of combinatorial replication-dependent histone variant genes
      during mouse spermatogenesis.
AB  - Nucleosomes are basic chromatin structural units that are formed by DNA sequences
      wrapping around histones. Global chromatin states in different cell types are
      specified by combinatorial effects of post-translational modifications of
      histones and the expression of histone variants. During mouse spermatogenesis,
      spermatogonial stem cells (SSCs) self-renew while undergo differentiation, events
      that occur in the company of constant re-modeling of chromatin structures.
      Previous studies have shown that testes contain highly expressed or specific
      histone variants to facilitate these epigenetic modifications. However,
      mechanisms of regulating the epigenetic changes and the specific histone
      compositions of spermatogenic cells are not fully understood. Using real time
      quantitative RT-PCR, we examined the dynamic expression of replication-dependent
      histone genes in post-natal mouse testes. It was found that distinct sets of
      histone genes are expressed in various spermatogenic cells at different stages
      during spermatogenesis. While gonocyte-enriched testes from mice at 2-dpp (days
      post partum) express pre-dominantly thirteen histone variant genes, SSC-stage
      testes at 9-dpp highly express a different set of eight histone genes. During
      differentiation stage when testes are occupied mostly by spermatocytes and
      spermatids, another twenty-two histone genes are expressed much higher than the
      rest, including previously known testis-specific hist1h1t, hist1h2ba and
      hist1h4c. In addition, histone genes that are pre-dominantly expressed in
      gonocytes and SSCs are also highly expressed in embryonic stem cells. Several of
      them were changed when embryoid bodies were formed from ES cells, suggesting
      their roles in regulating pluripotency of the cells. Further more, differentially
      expressed histone genes are specifically localized in either SSCs or
      spermatocytes and spermatids, as demonstrated by in situ hybridization using gene
      specific probes. Taken together, results presented here revealed that different
      combinations of histone variant genes are expressed in distinct spermatogenic
      cell types accompanying the progression of self-renewal and differentiation of
      SSCs, suggesting a systematic regulatory role histone variants play during
      spermatogenesis. 

PMID- 24140496
TI  - High selenium impairs hepatic insulin sensitivity through opposite regulation of
      ROS.
AB  - Insulin resistance is the hallmark of type 2 diabetes. As an essential trace
      element, selenium (Se) is recommended worldwide for supplementation to prevent Se
      deficient pathological conditions, including diabetes and insulin resistance.
      However, recent evidence has shown that supra-nutritional Se intake is positively
      associated with the prevalence of diabetes. In the present research, we examined
      the effect of high Se on insulin sensitivity, and studied possible mechanisms in
      rats and in rat hepatocytes. Insulin sensitivity and glucose/lipid metabolism
      were determined by glucose/insulin tolerance test, western blot,
      immunofluorescence, specific probes and other biochemical assays. We show that
      high Se activates selenoproteins, including glutathione peroxidase and
      selenoprotein P, and depletes chromium, leading to a common metabolic
      intersection-lipolysis in adipose tissue and influx of fatty acids in liver.
      Fatty acid beta-oxidation generates acetyl-CoA, which is metabolized in
      trichloroacetic acid cycle, supplying excessive electrons for mitochondrial
      oxidative phosphorylation and leading to increased "bad" reactive oxygen species
      (ROS) production in mitochondria and final disturbance of insulin signaling.
      Furthermore, high Se-activated selenoproteins also weaken insulin-stimulated
      "good" ROS signal generated by NAD(P)H oxidase, leading to attenuation of insulin
      signaling. Taken together, these data suggest that excessive intake of Se induces
      hepatic insulin resistance through opposite regulation of ROS. 

PMID- 24140497
TI  - Detection and simultaneous quantification of three smoking-related ethylthymidine
      adducts in human salivary DNA by liquid chromatography tandem mass spectrometry.
AB  - Smoking cigarette increases levels of certain ethylated DNA adducts in certain
      tissues and urine. Cigarette smoking is a major risk factor of various cancers
      and DNA ethylation is involved in smoking-related carcinogenesis. Among the
      ethylated DNA adducts, O(2)-ethylthymidine (O(2)-edT) and the promutagenic O(4)
      ethylthymidine (O(4)-edT) are poorly repaired and they can accumulate in vivo.
      Using an accurate, highly sensitive, and quantitative assay based on stable
      isotope dilution nanoflow liquid chromatography-nanospray ionization tandem mass
      spectrometry (nanoLC-NSI/MS/MS), O(2)-edT, N(3)-edT (N(3)-ethylthymidine), and
      O(4)-edT adducts in human salivary DNA were simultaneous detected and quantified.
      Saliva is easily accessible and available and it can be a potential target in
      searching for noninvasive biomarkers. Under the highly selected reaction
      monitoring (H-SRM) mode, salivary samples from 20 smokers and 13 nonsmokers were
      analyzed. Starting with 50 MUg of DNA isolated from about 3.5 mL of saliva,
      levels of O(2)-edT, N(3)-edT, and O(4)-edT in 20 smokers' salivary DNA samples
      were 5.3+/-6.2, 4.5+/-5.7, 4.2+/-8.0 in 10(8) normal nucleotides, respectively,
      while those in 13 nonsmokers were non-detectable. In addition, statistically
      significant correlations (p<0.0001) were observed between levels of O(2)-edT and
      N(3)-edT (gamma=0.7388), between levels of O(2)-edT and O(4)-edT (gamma=0.8839),
      and between levels of N(3)-edT, and O(4)-edT (gamma=0.7835). To the best of our
      knowledge, this is the first report of detection and quantification of these
      three ethylthymidine adducts in human salivary DNA, which might be potential
      biomarkers for exposure to ethylating agents and possibly for cancer risk
      assessment.

PMID- 24140498
TI  - Trivalent arsenic species induce changes in expression and levels of
      proinflammatory cytokines in intestinal epithelial cells.
AB  - Chronic arsenic (As) toxicity in humans has been documented in many countries
      where exposure mostly occurs through drinking water. The As immunotoxic effects
      have been demonstrated in animal models as well as in humans. The studies of the
      immunotoxicity of As have centered on organs related to immune response or target
      organs, with few data being available at intestinal level. The present study has
      evaluated the changes in the expression and release of cytokines in Caco-2 cells,
      widely used as an intestinal epithelial model. Differentiated cells were exposed
      to 1 MUM of As(III), 0.1 MUM of monomethylarsonous acid [MMA(III)] and 1 MUM of
      dimethylarsinous acid [DMA(III)] during 2, 4, 6 and 24 h. Additionally, the
      effect of As coexposure with lipopolysaccharide (LPS, 10 ng/mL) has been
      evaluated. The results show trivalent species to induce increases in the
      expression and release of the proinflammatory cytokines tumor necrosis factor
      alpha (TNFalpha), IL6, IL8 - the magnitude and time of response being different
      for each As species. The response of greatest magnitude corresponds to DMA(III),
      followed by As(III), while MMA(III) generates a limited response. Furthermore,
      the presence of LPS in the co-exposed cells could affect the expression and
      secretion of cytokines compared with individual exposure to arsenicals,
      especially for As(III)/LPS and DMA(III)/LPS.

PMID- 24140499
TI  - Chytrid mycoparasitism of entomophthoralean azygospores.
AB  - Mycoparasitism - when one fungus parasitizes another - has been reported to
      affect Beauveria bassiana and mycorrhizal fungi in the field. However,
      mycoparasitism of any fungi in the Order Entomophthorales has never been reported
      before now. The majority of entomophthoralean species persist as resting spores
      (either zygospores or azygospores) in the environment and dormant
      entomophthoralean resting spores (whether formed as zygospores or azygospores)
      are thought to be especially well adapted for survival over long periods due to
      their thick double walls. Entomophthoralean resting spores can accumulate in the
      soil as large reservoirs of inoculum which can facilitate the onset and
      development of epizootics. We report parasitism of azygospores of the gypsy moth
      pathogen Entomophaga maimaiga caged in soil from southern Ohio by the chytrid
      fungus Gaertneriomyces semiglobifer. G. semiglobifer had previously been isolated
      from soil samples from North America, Europe and Australia or horse manure from
      Virginia. After isolation and identification of G. semiglobifer, azygospores of
      E. maimaiga exposed to zoospores of G. semiglobifer exhibited high levels of
      mycoparasitism and G. semiglobifer was subsequently reisolated from
      mycoparasitized resting spores. We discuss the importance of this finding to the
      epizootiology of insect diseases caused by entomophthoralean fungi. 

PMID- 24140500
TI  - Nocardiosis in Mediterranean bivalves: first detection of Nocardia crassostreae
      in a new host Mytilus galloprovincialis and in Ostrea edulis from the Gulf of
      Naples (Italy).
AB  - In this work M. galloprovincialis and O. edulis specimens were surveyed for a
      pathological study in the Gulf of Naples (Mediterranean sea, Campania Region,
      southern Italy). Clusters of Nocardia sp.-like cells were observed in
      histological slides. PCR amplification, sequencing and in situ hybridization were
      carried out in order to corroborate Nocardia species identification for both
      hosts. Blast results showed a 99% of maximum identity with Nocardia crassostreae
      sequences in Genbank. This is the first report of N. crassostreae in the new host
      M. galloprovincialis and, in a new area, the Mediterranean Sea. 

PMID- 24140501
TI  - Seasonal dynamics of tick species in an urban park of Rome.
AB  - Regular collections were obtained in the Natural Reserve of the Insugherata of
      Rome during 2011 in order to obtain the tick species composition and the
      respective seasonal dynamics of the area. A total of 325 ticks was collected in
      selected sites by means of drag sampling. Among the identified species,
      Rhipicephalus turanicus was the most abundant (72.3%), followed by Ixodes ricinus
      (19.7%), Dermacentor marginatus (6.5%), Haemaphysalis punctata (1.2%), and
      Rhipicephalus bursa (0.3%). R. turanicus occurred mainly in pastures, showing a
      mono-modal seasonal activity pattern from spring to early summer. Questing I.
      ricinus were prevalent in woodland from October to May, and the seasonal trend of
      specimens showed a weak peak in winter. Although adult D. marginatus exhibited
      seasonal dynamics similar to I. ricinus, with an activity period from October to
      April, this species occurred in a different environment (pasture) and with
      considerably lower densities. Haemaphysalis punctata and R. bursa were rare, with
      an apparent autumn and autumn-winter seasonal activity, respectively. While the
      species diversity recorded appears as an unequivocal consequence of the natural
      state of the park, the remarkable R. turanicus density could be a direct effect
      of the recent introduction of wild boar, as carriers, from the close Veio Park.
      The presence of the species, a proven vector of various diseases in humans and
      domestic animals, is discussed in the light of the possible risk of tick-bite
      exposure of park workers and visitors. 

PMID- 24140502
TI  - A method to generate enhanced GFP+ chimeric mice to study the role of bone marrow
      derived cells in the eye.
AB  - GFP-chimeric mice are important tools to study the role of bone marrow-derived
      cells in eye physiology. A method is described to generate GFP-chimeric mice
      using whole-body, sub-lethal radiation (600 rad) of wild-type C57BL/6 recipients
      followed by tail vein injection of bone marrow cells derived from GFP+ (GFP
      transgenic C57/BL/6-Tg(UBC-GFP)30 Scha/J) mice. This method yields stable GFP+
      chimeras with greater than 95% chimerism (range 95-99%), achieved within one
      month of bone marrow transfer confirmed by microscopy and fluorescence-assisted
      cell sorting (FACS) analysis, with lower mortality after irradiation than prior
      methods. To demonstrate the efficacy of GFP+ bone marrow chimeric mice, the role
      of circulating GFP+ bone marrow-derived cells in myofibroblast generation after
      irregular photo-therapeutic keratectomy (PTK) was analyzed. Many SMA+
      myofibroblasts that were generated at one month after PTK were derived from GFP+
      bone marrow-derived cells. The GFP+ bone marrow chimeric mouse provides an
      excellent model for studying the role of bone marrow-derived cells in corneal
      wound healing, glaucoma surgery, optic nerve head pathology and retinal
      pathophysiology and wound healing. 

PMID- 24140503
TI  - Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like
      behavior.
AB  - Prostacyclin is an endogenous lipid metabolite with properties of vasodilation
      and anti-platelet aggregation. While the effects of prostacyclin on the vascular
      protection have been well-documented, the role of this eicosanoid in the central
      nervous system has not been extensively studied. Recently, a transgenic mouse
      containing a hybrid enzyme, of cyclooxygenase-1 linked to prostacyclin synthase,
      was developed that produces elevated levels of prostacyclin in vivo. The goal of
      this study was to investigate whether increased prostacyclin biosynthesis could
      affect behavioral phenotypes in mice. Our results uncovered that elevated levels
      of prostacyclin broadly affect both cognitive and non-cognitive behaviors,
      including decreased anxiety-like behavior and improved learning in the fear
      conditioning memory test. This study demonstrates that prostacyclin plays an
      important, but previously unrecognized, role in central nervous system function
      and behavior. 

PMID- 24140504
TI  - Increased oxidative stress in prefrontal cortex and hippocampus is related to
      depressive-like behavior in streptozotocin-diabetic rats.
AB  - Depression is a common comorbid in diabetic patients. The pathophysiologic
      mechanisms that relate this comorbidity is not completely elucidated yet,
      although several lines of evidence point out that increased oxidative stress
      resulting from hyperglycemia may have a crucial role. Thus, the effect of
      prolonged treatment with insulin (INS), the antioxidant vitamin E (VIT E) or the
      antidepressant imipramine (IMI) was evaluated in animals submitted to forced
      swimming test. Oxidative stress parameters (lipid peroxidation product levels,
      reduced gluthatione levels and catalase and superoxide dismutase activities) were
      also evaluated in brain areas related to depression, prefrontal cortex (PFC) and
      hippocampus (HIP). Our data show that treatment of streptozotocin-induced
      diabetic (DBT) rats with INS (6 UI/day, s.c.) prevented the blood glucose
      increase, reduced the immobility time, an antidepressant-like behavior, and
      normalized the reduced weight gain. Although the VIT E treatment (300 mg/kg,
      p.o.) had not altered the blood glucose levels, this treatment was able to reduce
      the immobility time and to reestablish the reduced weight gain in DBT rats.
      Differently, treatment with IMI (15 mg/kg, i.p.) induced antidepressant-like
      behavior in normoglycemic besides DBT animals. While VIT E and IMI treatments
      restored only specific oxidative stress parameters, INS was able to prevent all
      changed parameters evaluated in both PFC and HIP from DBT animals. Therefore, our
      data provide further evidence of the importance of oxidative stress in PFC and
      HIP in the pathophysiology of depression related to diabetes.

PMID- 24140505
TI  - Disruption of the bronchodilatory response to deep inspiration in asthma-
      extrinsic or intrinsic to the airway smooth muscle?

PMID- 24140506
TI  - Impact of stepwise mandibular advancement on upper airway mechanics in
      obstructive sleep apnea using phrenic nerve magnetic stimulation.
AB  - Mandibular advancement devices (MAD) represent a potential treatment for
      obstructive sleep apnea (OSA). However, their mechanisms of actions are not
      completely understood. This study was aimed to explore the effects of MAD-induced
      mandibular protrusion on upper airway mechanics. 25 men commencing treatment for
      OSA with MAD were recruited. Phrenic nerve magnetic stimulation (PNMS) was used
      to measure flow/pressure relationship during progressive protrusion in three
      conditions (without MAD, MAD at minimum protrusion, and MAD at maximum tolerable
      protrusion). Pressures were recorded simultaneously at three different upper
      airway segments (naso-, velo-, and oro-pharynx). Without MAD, PNMS twitches
      induced flow-limitation at the velopharyngeal level in 19 subjects and six of
      them experienced a shift in the flow-limitation site to the lower segment with
      MAD at maximum protrusion. An association was found between having a
      velopharyngeal limitation site without MAD and the increase in maximum flow with
      the advanced MAD. These data suggest that mandibular advancement devices are
      acting predominantly at the velopharyngeal level. 

PMID- 24140507
TI  - [Statins and the risk of diabetes].
AB  - Statins have a relevant role in decreasing cardiovascular mortality. Statins are
      effective in primary and secondary prevention. Recently, it has been suggested
      that statins may have a diabetogenic effect, because a moderate increase in the
      risk of newly developed diabetes mellitus was observed. The diabetogenic effect
      of statins is a group effect and it is dose-dependent, too. The effect of statins
      which lower the cardiovascular risk attenuates the risk of developing diabetes
      during statin therapy, too. Hence, statins remain the first line therapy of
      reaching LDL-cholesterol targets.

PMID- 24140508
TI  - [Clinical consequence and significance of anti-neutrophil cytoplasmic antibody
      positivity in anti-glomerular basement membrane disease].
AB  - INTRODUCTION: Patients with renopulmonary syndrome who have both anti-neutrophil
      cytoplasmic and anti-glomerular basement membrane antibodies have been described
      since 1989. AIM: The aim of the authors was to analyse the data of "double
      positive" patients diagnosed in their department, and compare these with previous
      studies. METHOD: During the last 16 years, 87 anti-neutrophil cytoplasmic
      antibody positive and 11 anti-glomerular basement membrane antibody positive
      patients were diagnosed. Four patients with anti-glomerular basement membrane
      antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2
      patients were positive for anti-myeloperoxidase and 2 patients for anti
      proteinase 3. RESULTS: In comparison with patients having anti-glomerular
      basement membrane antibodies, the double-positive patients were characterized by
      older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more
      frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti
      glomerular basement membrane antibody levels (<100EU/ml: 100% vs. 29%). The
      double-positive patients had more favourable 1-year survival (100% vs. 71%),
      despite their older age and similar treatment regimen (immunosuppression 100% in
      both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not
      different (25% vs. 14%). CONCLUSIONS: In agreement with literature data, about
      one third of patients with anti-glomerular basement membrane antibodies had
      detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two
      antibodies may have clinical consequences.

PMID- 24140509
TI  - [Frequency and characteristics of granulomas in 368 pediatric patients with
      Crohn's disease].
AB  - INTRODUCTION: Epitheloid granulomas are one of the best histological criteria for
      distinguishing Crohn's disease from other inflammatory bowel diseases. However,
      the role of granuloma in the pathogenesis and clinical characteristics of Crohn's
      disease is unclear. AIM: The aim of the present study was to evaluate the
      frequency of granulomas and their association with clinical characteristics using
      the database of the Hungarian Pediatric Inflammatory Bowel Disease Registry.
      METHOD: Three hundred and sixty-eight children with Crohn's disease were
      registered between January 1st, 2007 and December 31st, 2010. RESULTS: The
      frequency of granulomas was 31.4% (111/353) at diagnosis. Isolated granuloma in
      the upper gastrointestinal tract was detected in 2.5% of patients, while those in
      the terminal ileum was found in 5% of patients. There was no difference in
      location, behavior and disease activity indexes between patients with and without
      granulomas. Need for immunomodulators and biological therapy was similar in the
      two groups in the first year of diagnosis. CONCLUSIONS: The frequency of
      granulomas in this cohort was comparable to the frequency reported in other
      studies. Interestingly, granulomas in the terminal ileum or upper
      gastrointestinal tract contributed to the diagnosis of Crohn's disease in one of
      13 children. These data indicate that multiple biopsies from multiple sites are
      essential for the diagnosis of pediatric Crohn's disease.

PMID- 24140510
TI  - [Comparison of SCORE and Reynolds cardiovascular risk assessments in a cohort
      without cardiovascular disease].
AB  - INTRODUCTION: Cardiovascular risk assessment may help in the identification of
      symptom-free subjects with high cardiovascular risk. AIM: The author studied the
      correlation between SCORE and Reynolds risk assessment systems based on data from
      the cardiovascular risk screening program carried out in subjects without
      cardiovascular disease. METHOD: Data obtained from 4462 subjects (1977 men and
      2485 women; mean age, 47,4 years) were analysed. The comparison was based on risk
      categories of the SCORE system. RESULTS: There was a strong correlation between
      the two scoring systems in the low risk population (under <2% SCORE risk the
      Spearman rho = 1, p < 0.001). A weak correlation was found in the medium risk
      group (between 3-4% the Spearman rho = 0.59-0.49, p < 0.001 and between 10-14%
      the Spearman rho = 0.42, ns.) and a stronger correlation in the high risk group
      (>15% the Spearmen rho = 0.8, p = 0.017). When correlations were analysed in
      gender and age categories, the weakest correlation was detected in medium risk
      women over 40 years of age. In cases when the differences between the two scoring
      systems were significant, the hsCRP levels were significantly higher (4.1 vs.
      5.67 mg/L, p < 0.001). CONCLUSIONS: Introduction of hsCRP into cardiovascular
      risk assessments can refine the risk status of symptom-free subjects, especially
      among intermediate risk middle-age women (two-step risk assessment).

PMID- 24140511
TI  - [Patient satisfaction with care in gastrooesophageal reflux disease].
AB  - INTRODUCTION: Besides medical treatment, adequate communication and personal
      relationships between physicians and patients are the most important determinants
      of patient satisfaction. AIM: To explore doctor-patient relationships, and
      factors that may determine patient satisfaction with care. METHOD: Patients with
      gastroesophageal reflux (n = 80) were divided into subgroups treated by family
      doctors or by gastroenterologists. Patients were asked to fill in a questionnaire
      about communication and patient satisfaction. RESULTS: Significantly more
      patients visited family doctors than gastroenterologists with health problems
      (80%; 20%, p < 0.001). Patients were significantly more satisfied with the
      information they received about the process of care provided by family doctors
      (95%) compared to that they obtained from gastroenterologists (65%; p = 0.002).
      Significantly more patients in family practices indicated that their doctors
      spent enough time with them compared to subspecialists (96.7%; 80% p = 0.032).
      CONCLUSIONS: Patients develop a closer personal relationship and more appropriate
      communication with family doctors compared to specialists, which can be an
      important component of successful treatment.

PMID- 24140512
TI  - [Healthcare experience of a Hungarian physician, living in England].

PMID- 24140514
TI  - Development of a FACS-based assay for evaluating antiviral potency of compound in
      dengue infected peripheral blood mononuclear cells.
AB  - Dengue fever is the most important arthropod-transmitted viral disease affecting
      humans. It is a blood-borne disease characterized by persistent fever and joint
      pain. In the blood, primary peripheral blood mononuclear cells (PBMCs), in
      particular monocytes, are the main target of the dengue virus (DENV). These cells
      are poorly permissive for in vitro dengue virus infection and their infectivity
      varies from donor to donor. To overcome this barrier, an anti-dengue antibody was
      used to improve the infectivity of DENV-2 clinical isolates to PBMCs, the
      monocytic leukemia cell line, THP-1 and the granulocyte cell line, KU812. A
      higher throughput 96-well-format assay based on a fluorescent-activated cell
      sorter could potentially be developed to evaluate the antiviral potency of
      compounds in DENV-infected PBMCs in vitro. The results correlate well with data
      obtained by a standard plaque assay. Altogether, an assay has been developed that
      enables evaluation of the antiviral activity of test compounds in a
      physiologically-relevant cell system (PBMCs). These screening processes are
      urgently needed for dengue drug discovery. 

PMID- 24140513
TI  - Toll-like receptor 3 plays a role in myocardial infarction and
      ischemia/reperfusion injury.
AB  - Innate immune and inflammatory responses mediated by Toll like receptors (TLRs)
      have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study
      examined the role of TLR3 in myocardial injury induced by two models, namely,
      myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI.
      TLR3 deficient (TLR3(-/-)) and wild type (WT) mice were subjected to MI induced
      by permanent ligation of the left anterior descending (LAD) coronary artery for
      21days. Cardiac function was measured by echocardiography. Next, we examined
      whether TLR3 contributes to myocardial I/R injury. TLR3(-/-) and WT mice were
      subjected to myocardial ischemia (45min) followed by reperfusion for up to 3days.
      Cardiac function and myocardial infarct size were examined. We also examined the
      effect of TLR3 deficiency on I/R-induced myocardial apoptosis and inflammatory
      cytokine production. TLR3(-/-) mice showed significant attenuation of cardiac
      dysfunction after MI or I/R. Myocardial infarct size and myocardial apoptosis
      induced by I/R injury were significantly attenuated in TLR3(-/-) mice. TLR3
      deficiency increases B-cell lymphoma 2 (BCL2) levels and attenuates I/R-increased
      Fas, Fas ligand or CD95L (FasL), Fas-Associated protein with Death Domain (FADD),
      Bax and Bak levels in the myocardium. TLR3 deficiency also attenuates I/R-induced
      myocardial nuclear factor KappaB (NF-kappaB) binding activity, Tumor necrosis
      factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1beta) production as well as
      I/R-induced infiltration of neutrophils and macrophages into the myocardium. TLR3
      plays an important role in myocardial injury induced by MI or I/R. The mechanisms
      involve activation of apoptotic signaling and NF-kappaB binding activity.
      Modulation of TLR3 may be an effective approach for ameliorating heart injury in
      heart attack patients. 

PMID- 24140515
TI  - A novel method using Autographa californica multiple nucleopolyhedrovirus for
      increasing the sensitivity of insecticide through calcium influx in insect cell
      line.
AB  - Due to an intensive use of chemical insecticides, resistance mechanisms to
      insecticides together with adverse effects on non-target organisms have been
      largely reported. Improvement in pest control strategy represents an urgent need
      to optimize efficiency in the control of pest insects. In this context, a novel
      method based on the use of insect specific virus applied in combination with
      chemical insecticide, which could lead to sensitization of the insect target to
      insecticides is described. Insect virus, the baculovirus Autographa californica
      multiple nucleopolyhedrovirus (AcMNPV), applied onto Sf9 cells induces an
      increase of intracellular calcium concentration via extracellular calcium influx.
      Co-application of AcMNPV with chlorpyrifos-ethyl onto Sf9 cells expressing the
      key enzyme acetylcholinesterase (AChE), known to be targeted by organophosphate
      insecticides, increases 1.5-fold the sensitivity of AChE to the insecticide. This
      effect is correlated with intracellular calcium concentration rise since AcMNPV
      induced potentiating insecticide effect is counteracted by pretreatment with the
      calcium channel blocker, cadmium chloride. Increasing insecticide target
      sensitivity through intracellular calcium modulation by using insect virus co
      applied with a chemical insecticide is a very promising strategy allowing
      optimization of insecticide treatment while reducing the concentration of
      insecticides used. 

PMID- 24140516
TI  - Comparison of cardiorespiratory and EEG abnormalities with seizures in adults and
      children.
AB  - Cardiopulmonary dysfunction and postictal generalized EEG suppression (PGES) are
      proposed as possible risk factors for the occurrence of SUDEP. The evolution of
      cardiorespiratory abnormalities with seizures has not been systematically studied
      for any age-related findings. Additionally, not many studies have looked into the
      possible effect of age-related brain maturation on PGES. The purpose of this
      study was to compare these SUDEP risk factors in adults versus children. We
      prospectively recorded cardiopulmonary abnormalities during seizures using pulse
      oximetry, EKG, and respiratory inductance plethysmography. Linear and logistic
      regression models adjusting for multiple seizures in a single patient were used
      to compare the cardiorespiratory and EEG findings between adults and children. We
      recorded 101 seizures in 26 children and 55 seizures in 22 adults. Ictal central
      apnea and bradycardia occurred more often in children than in adults (p=0.02 and
      p=0.008, respectively), while ictal tachycardia occurred more often in adults
      (p=0.001) than in children. Postictal generalized EEG suppression of longer
      duration occurred more often in adults (p=0.003) than in children. Minimum O2
      saturation and seizure duration/generalization/lateralization did not
      significantly differ between adults and children (p>0.1). Children had more
      frontal lobe seizures, and adults had more temporal lobe seizures recorded
      (p=0.01). There may be an age-related effect on cardiorespiratory and EEG
      abnormalities associated with seizures, with higher rates of apnea and
      bradycardia in children and a much higher prevalence of PGES of longer duration
      in adults. This may indicate why, despite lower rates of cardiopulmonary
      dysfunction, adults die more frequently from SUDEP than children. 

PMID- 24140517
TI  - Epilepsy as a pathology of consciousness.

PMID- 24140518
TI  - The optimal segment for spinal cord stimulation in intractable epilepsy: a
      virally mediated transsynaptic tracing study in spinally transected transgenic
      mice.

PMID- 24140519
TI  - Concentrations and bioaccessibilities of trace elements in barbecue charcoals.
AB  - Total and bioaccessible concentrations of trace elements (Al, As, Cd, Cu, Fe, Hg,
      Mn, Ni, Pb and Zn) have been measured in charcoals from 15 barbecue products
      available from UK retailers. Total concentrations (available to boiling aqua
      regia) were greater in briquetted products (with mean concentrations ranging from
      0.16 MUg g(-1) for Cd to 3240 MUg g(-1) for Al) than in lumpwoods (0.007 MUg g(
      1) for Cd to 28 MUg g(-1) for Fe), presumably because of the use of additives and
      secondary constituents (e.g. coal) in the former. On ashing, and with the
      exception of Hg, elemental concentrations increased by factors ranging from about
      1.5 to 50, an effect attributed to the combustion of organic components and
      offset to varying extents by the different volatilities of the elements.
      Concentrations in the ashed products that were bioaccessible, or available to a
      physiologically based extraction test (PBET) that simulates, successively, the
      chemical conditions in the human stomach and intestine, exhibited considerable
      variation among the elements studied. Overall, however, bioaccessible
      concentrations relative to corresponding total concentrations were greatest for
      As, Cu and Ni (attaining 100% in either or both simulated PBET phases in some
      cases) and lowest for Pb (generally <1% in both phases). A comparison of
      bioaccessible concentrations in ashed charcoals with estimates of daily dietary
      intake suggest that Al and As are the trace elements of greatest concern to human
      health from barbecuing.

PMID- 24140520
TI  - Enhanced xylene removal by photocatalytic oxidation using fiber-illuminated
      honeycomb reactor at ppb level.
AB  - The removal of volatile organic compounds (VOCs) at ppb level is one of the most
      critical challenges in clean rooms for the semiconductor industry. Photocatalytic
      oxidation is an innovative and promising technology for ppb-level VOCs
      degradation. We have designed a fiber-illuminated honeycomb reactor (FIHR) in
      which the removal efficiency of m-xylene is significantly enhanced to 96.5% as
      compared to 22.0% for UV irradiation only. The results indicate that
      photocatalysts not only play the role to substantially oxidize m-xylene, but also
      alter the chemical properties of xylene under UV illumination. Using the FIHR
      with Mn-TiO2 photocatalyst not only increased the m-xylene removal efficiency,
      but also increased the CO2 selectivity. Interestingly, Mn-TiO2 in FIHR also
      showed a very good reusability, 93% removal efficiency was still achieved in 72-h
      in reaction. Thus, the FIHR gave very high removal efficiency for xylene at ppb
      level under room temperature. The FIHR has great potential application in the
      clean room for the air purification system in the future. 

PMID- 24140521
TI  - Toxicity of perfluorooctanoic acid to Pseudomonas putida in the aquatic
      environment.
AB  - Perfluorinated compounds are potential persistent organic pollutants which
      attracted much concerns in recent years. Thus relevant toxicity data of
      perfluorooctanoic acid (PFOA) are vitally important for identification of
      possible risk in the aquatic environment. In the present study, the acute toxic
      effect of PFOA in the absence and presence of either chromium (III) or tetra
      butyl ammonium (TBA) towards Pseudomonas putida in the aquatic environment was
      investigated by microcalorimetry. The thermokinetic parameters including growth
      rate constant (k), inhibitory ratio, and half inhibitory concentration, were
      calculated and compared using the data obtained from the power-time curves. Our
      work revealed the toxicity of PFOA under three experimental conditions in a
      descending sequence: PFOA, PFOA+Cr(3+), and PFOA+TBA. The results highlighted
      that the presence of un-ionized NH3 in the test solutions could not be a
      potential significant contributor to the observed toxicity of PFOA. In addition,
      PFOA interacted antagonistically with Cr(3+) and TBA. TBA was found to
      substantially enhance the surface pressure of PFOA which could be related with
      the toxicity of PFOA. The higher surface pressure caused for the reduction in
      toxicity. Thus the results highlighted the potential toxicological risk
      associated with this surfactant in the aquatic ecosystems. 

PMID- 24140522
TI  - By-passing acidification limitations during the biofiltration of high
      formaldehyde loads via the application of ozone pulses.
AB  - A formaldehyde airstream was treated in a biofilter for an extended period of
      time. During the first 133 days, the reactor was operated without ozone, whereas
      over the following 82 days ozone was intermittently implemented. The maximum
      stable elimination capacity obtained without ozone was around 57 g m(-3) h(-1). A
      greater load could not be treated under these conditions, and no significant
      formaldehyde removal was maintained for inlet loads greater than 65 g m(-3) h(
      1); the activity of microorganisms was then inhibited by the presence of acidic
      byproducts, and the media acidified (pH<4). The implementation of ozone pulses
      allowed a stable elimination capacity to be obtained, even at greater loads (74 g
      m(-3) h(-1)). The effect of ozone on the extra cellular polymeric substances
      detachment from the biofilm could not be confirmed due to the too low biofilter
      biomass content. Thus, the results suggest that ozone acted as an in situ pH
      regulator, preventing acidic byproducts accumulation, and allowing the treatment
      of high loads of formaldehyde.

PMID- 24140523
TI  - Past and future cadmium emissions from municipal solid-waste incinerators in
      Japan for the assessment of cadmium control policy.
AB  - Cadmium (Cd) is a harmful pollutant emitted from municipal solid-waste
      incinerators (MSWIs). Cd stack emissions from MSWIs have been estimated between
      1970 and 2030 in Japan. The aims of this study are to quantify emitted Cd by
      category and to analyze Cd control policies to reduce emissions. Emissions were
      estimated using a dynamic substance flow analysis (SFA) that took into account
      representative waste treatment flows and historical changes in emission factors.
      This work revealed that the emissions peaked in 1973 (11.1t) and were ten times
      those in 2010 (1.2 t). Emission from MSWIs was two-thirds of that from non
      ferrous smelting in 2010. The main Cd emission source was pigment use in the
      1970s, but after 2000 it had shifted to nickel-cadmium (Ni-Cd) batteries. Future
      emissions were estimated for 2030. Compared to the business-as-usual scenario, an
      intensive collection of used Ni-Cd batteries and a ban on any future use of Ni-Cd
      batteries will reduce emissions by 0.09 and 0.3 1t, respectively, in 2030. This
      approach enables us to identify the major Cd emission source from MSWIs, and to
      prioritize the possible Cd control policies.

PMID- 24140524
TI  - Fe(0)-Fe3O4 nanocomposites embedded polyvinyl alcohol/sodium alginate beads for
      chromium (VI) removal.
AB  - In this study, Fe(0)-Fe3O4 nanocomposites embedded polyvinyl alcohol (PVA)/sodium
      alginate (SA) beads were synthesized, which exhibited an excellent physical
      properties and catalytic reactivity, and a robust performance of post-separation
      (complete separation using a simple grille) and reusability (efficiency of 69.8%
      after four runs) in Cr(VI) removal. 5.0 wt% PVA with 1.5 wt% SA was the optimal
      proportion for beads molding, and the followed acidification and reduction
      treatments were critical to ensure high mechanical strength and high Cr(VI)
      removal ability of beads. Effects of Fe(0) and Fe3O4 mass fraction, initial pH
      and Cr(VI) concentration on final removal efficiency were also evaluated. Merely
      0.075 wt% Fe(0) together with 0.30 wt% Fe3O4 was sufficient to deal with 20 mg L(
      1) Cr(VI) solution. The efficiency decreased from 100 to 79.5% as initial Cr(VI)
      increased from 5 to 40 mg L(-1), while from 99.3 to 76.3% with increasing pH from
      3.0 to 11.0. This work provides a practical and high-efficient method for heavy
      metal removal from water body, and simultaneously solves the problems in
      stabilization, separation and regeneration of Fe(0) nanoparticles.

PMID- 24140525
TI  - Chlorine and hydrogen cyanide gas interactions with human skin: in vitro studies
      to inform skin permeation and decontamination in HAZMAT incidents.
AB  - Accidental or intentional toxic gas releases may result in significant public
      health and psychological consequences. Management of exposed individuals during
      HAZMAT incidents should be risk-based and supported by a suitable scientific
      evidence base. There appear to be large evidence gaps in relation to dermal
      absorption of gases, as well as management advice for potentially exposed
      individuals. Chlorine and hydrogen cyanide are two common HAZMAT gases and this
      paper addresses the need for experimental data tailored to HAZMAT scenarios and
      first responders. In addition to time variations of gas concentration, the
      modifying effects of clothing, temperature, and oil-based sunscreen on epidermal
      absorption and penetration are assessed. Results for chlorine show little
      penetration up to 500 ppm but with small enhancing effects due to heavy cotton
      and oil-based sunscreen. Hydrogen cyanide up to 800 ppm shows minor penetration
      consistent with previous studies, with little variability in the presence of
      sunscreen and clothing. Practical guidelines to support the decision-making of
      emergency responders with regard to personal decontamination have been derived.

PMID- 24140526
TI  - Facile preparation of Ni(OH)2-MnO2 hybrid material and its application in the
      electrocatalytic oxidation of hydrazine.
AB  - A surfactant-free synthetic methodology is reported for the preparation of
      Ni(OH)2-MnO2 hybrid nanostructures. For comparative study, MnO2 and Ni(OH)2 were
      also synthesized. Materials were characterized by X-ray diffraction, nitrogen
      sorption, scanning electron microscopy, and transmission electron microscopy.
      Ni(OH)2-MnO2 modified electrode is fabricated for the determination of hydrazine.
      The electrochemical oxidation of hydrazine was investigated using cyclic, linear
      sweep voltammetries, and chronoamperometry methods. The Ni(OH)2-MnO2 modified
      electrode showed hydrazine oxidation with decrease in the over voltage and
      increase in the oxidation peak current, when compared to MnO2, Ni(OH)2, and bare
      GCE. pH was optimized to obtain the best peak potential and current sensitivity.
      Chronoamperometry was used to estimate the diffusion coefficient of hydrazine.
      The kinetic parameters such as overall number of electrons involved in the
      catalytic oxidation of hydrazine and the rate constant (k) for the oxidation of
      hydrazine at Ni(OH)2-MnO2 modified electrode were determined. The Ni(OH)2-MnO2
      modified electrode exhibited good sensitivity, stability, and reproducibility in
      hydrazine sensing. 

PMID- 24140527
TI  - Electro-regeneration of Ce(IV) in real spent Cr-etching solutions.
AB  - This paper presents the electro-regeneration of Ce(IV) in real (hazardous) spent
      thin-film transistor liquid-crystal display (TFT-LCD) Cr-etching solutions. In
      addition to Ce(III)>Ce(IV) in diffusivity, a quasi-reversible behavior of
      Ce(III)/Ce(IV) was observed at both boron-doped diamond (BDD) and Pt disk
      electrodes. The Ce(IV) yield on Pt increased with increasing current density, and
      the best current efficiency (CE) was obtained at 2A/2.25 cm(2). The performance
      in terms of Ce(IV) yield and CE of tested anodes was in order BDD>Pt>dimensional
      stable anode (DSA). At 2A/2.25 cm(2) on Pt and 40  degrees C for 90 min, the
      Ce(IV) yield, CE and apparent rate constant (k) for Ce(III) oxidation were 81.4%,
      21.8% and 3.17 * 10(-4) s(-1), respectively. With the increase of temperature,
      the Ce(IV) yield, CE, and k increased (activation energy = 10.7 kJ/mol), but the
      specific electricity consumption decreased. The Neosepta CMX membrane was more
      suitable than Nafion-117 and Nafion-212 to be used as the separator of the Ce(IV)
      regeneration process. The obtained parameters are useful to design divided batch
      reactors for the Ce(IV) electro-regeneration in real spent Cr-etching solutions.

PMID- 24140528
TI  - Comparison of preparation methods for ceria catalyst and the effect of surface
      and bulk sulfates on its activity toward NH3-SCR.
AB  - A series of CeO2 catalysts prepared with sulfate (S) and nitrate (N) precursors
      by hydrothermal (H) and precipitation (P) methods were investigated in selective
      catalytic reduction of NOx by NH3 (NH3-SCR). The catalytic activity of CeO2 was
      significantly affected by the preparation methods and the precursor type. CeO2
      SH, which was prepared by hydrothermal method with cerium (IV) sulfate as a
      precursor, showed excellent SCR activity and high N2 selectivity in the
      temperature range of 230-450  degrees C. Based on the results obtained by
      temperature-programmed reduction (H2-TPR), transmission infrared spectra (IR) and
      thermal gravimetric analysis (TGA), the excellent performance of CeO2-SH was
      correlated with the surface sulfate species formed in the hydrothermal reaction.
      These results indicated that sulfate species bind with Ce(4+) on the CeO2-SH
      catalyst, and the specific sulfate species, such as Ce(SO4)2 or CeOSO4, were
      formed. The adsorption of NH3 was promoted by these sulfate species, and the
      probability of immediate oxidation of NH3 to N2O on Ce(4+) was reduced.
      Accordingly, the selective oxidation of NH3 was enhanced, which contributed to
      the high N2 selectivity in the SCR reaction. However, the location of sulfate on
      the CeO2-SP catalyst was different. Plenty of sulfate species were likely
      deposited on CeO2-SP surface, covering the active sites for NO oxidation, which
      resulted in poor SCR activity in the test temperature range. Moreover, the
      resistance to alkali metals, such as Na and K, was improved over the CeO2-SH
      catalyst.

PMID- 24140529
TI  - Decomposition of 2-chloroethylethylsulfide on copper oxides to detoxify polymer
      based spherical activated carbons from chemical warfare agents.
AB  - For the decomposition of chemical warfare agents, a hybrid material concept was
      applied. This consists of a copper oxide-containing phase as a component with
      reactive functionality supported on polymer-based spherical activated carbon
      (PBSAC) as a component with adsorptive functionality. A corresponding hybrid
      material was prepared by impregnation of PBSAC with copper(II)nitrate and
      subsequent calcination at 673K. The copper phase exists predominantly as
      copper(I)oxide which is homogeneously distributed over the PBSAC particles. The
      hybrid material containing 16 wt.% copper on PBSAC is capable of self-detoxifying
      the mustard gas surrogate 2-chloroethylethylsulfide (CEES) at room temperature.
      The decomposition is related to the breakthrough behavior of the reactant CEES,
      which displaces the reaction product ethylvinylsulfide (EVS). This leads to a
      combined breakthrough of CEES and EVS. The decomposition of CEES is shown to
      occur catalytically over the copper-containing PBSAC material. Thus, the hybrid
      material can even be considered to be self-cleaning.

PMID- 24140530
TI  - Growth, physiological response and phytoremoval capability of two willow clones
      exposed to ibuprofen under hydroponic culture.
AB  - Ibuprofen (IBU) is one of the most widespread pharmaceuticals in the aquatic
      ecosystem, despite the high removal rate that occurs in wastewater treatment
      plants. Phytoremediation represents a technology to improve the performance of
      existing wastewater treatment. This study was conducted under hydroponics to
      evaluate the ability of Salicaceae plants to tolerate and reduce IBU
      concentration in contaminated water. To this end, we combined growth,
      physiological and biochemical data to study the effects of different IBU
      concentrations on two clones of Salix alba L. Data demonstrated that clone SS5
      was more tolerant and showed a higher ability to reduce IBU concentration in the
      solution than clone SP3. The high tolerance to IBU shown by SS5 was likely due to
      several mechanisms including the capacity to maintain an elevated photosynthetic
      activity and an efficient antioxidative defence. These results illustrate the
      remarkable potential of willow to phytoremediate IBU-contaminated waters in
      natural and constructed wetlands. 

PMID- 24140531
TI  - Influence of Cu and Ca cations on ciprofloxacin transport in saturated porous
      media.
AB  - Emerging contaminant ciprofloxacin (CIP) has been frequently detected in soils
      and groundwater; however, impacts of cations on its transport in the environment
      remain largely unknown. We examined CIP transport in saturated sand media under
      the influence of Cu/Ca by either mixing CIP with Cu/Ca in solution or preloading
      CIP onto sand then using Cu/Ca solution to mobilize CIP. Though the amount of
      Fe/Al oxides on native sand surface was limited, it significantly impeded CIP
      transport, delaying CIP breakthrough curve from 30 to >100 PV. In clean sand
      where Fe/Al oxides were removed, Ca and Cu significantly promoted CIP transport
      by reducing the retardation factor R from 22 to <2. In native sand, due to CIP's
      strong complexation with Fe/Al, only Cu promoted CIP transport. When CIP was pre
      sorbed onto sand, neither Cu nor Ca was effective in mobilizing CIP from native
      sand. However, Cu effectively mobilized 90% CIP whereas Ca mobilized 30% CIP from
      clean sand. A mathematical model based on advection-dispersion equation coupled
      with equilibrium and kinetic reactions successfully simulated CIP transport in
      saturated sand media. Our results suggested that cations in aqueous solution and
      on solid phase are important to better understand CIP transport in soils.

PMID- 24140532
TI  - Evidence of superoxide radical contribution to demineralization of
      sulfamethoxazole by visible-light-driven Bi2O3/Bi2O2CO3/Sr6Bi2O9 photocatalyst.
AB  - Photocatalytic degradation of sulfamethoxazole (SMX) was investigated using
      Bi2O3/Bi2O2CO3/Sr6Bi2O9 (BSO) photocatalyst under visible light (>420 nm)
      irradiation. The photochemical degradation of SMX followed pseudo-first-order
      kinetics. The reaction kinetics was determined as a function of initial SMX
      concentrations (5-20 mg L(-1)), initial pH (3-11) and BSO concentrations (6-600
      mg L(-1)). Approximately, 90% of SMX (10 mg L(-1)) degradation and 36% of TOC
      reduction were achieved at pH 7.0 after 120 min irradiation. The main
      mineralization products, including NH4(+), NO3(-), SO4(2-) and CO2, as well as
      intermediates 3-amino-5-methylisoxazole (AMI), p-benzoquinone (BZQ), and
      sulfanilic acid (SNA) were detected in aqueous solution. The formation of O2(*-)
      radical was evidenced by using electron spin resonance and a chemiluminescent
      probe, luminal. A possible degradation mechanism involving excitation of BSO,
      followed by charge injection into the BSO conduction band and formation of
      reactive superoxide radical (O2(*-)) was proposed for the mineralization of SMX.
      During the reaction, the O2(*-) radical attacks the sulfone moiety and causes the
      cleavage of the SN bond, which leads to the formation of two sub-structure
      analogs, AMI and SNA.

PMID- 24140533
TI  - Functional clay supported bimetallic nZVI/Pd nanoparticles used for removal of
      methyl orange from aqueous solution.
AB  - Bentonite supported Fe/Pd nanoparticles (B/nZVI/Pd) were synthesized as
      composites that exhibit functionalities assisting in the removal of methyl orange
      (MO) from aqueous solution. The results showed that 91.87% of MO was removed
      using B/nZVI/Pd, while only 85% and 1.41% of MO were removed using nZVI/Pd and
      bentonite after 10 min, respectively. The new findings include that the presence
      of bentonite decreased the aggregation of nZVI/Pd and nZVI in the composite
      played its role as a reductant, while Pd(0) acted as the catalyst to enhance the
      degradation of MO, which were confirmed by scanning electron microscopy (SEM), X
      ray diffraction (XRD), UV-vis analysis and the batch experiments. The increase in
      B/nZVI/Pd loading led to greater removal efficiency, while decolorization
      efficiency declined in the presence of anions such as nitrate, sulfite and
      carbonate, especially nitrate, which decreased the apparent rate constant k(obs)
      almost 17.06-fold. The kinetics study indicated that the degradation of MO fitted
      well to the pseudo-first-order model, where the k(obs) was 0.0721 min(-1).
      Finally, the reactivity of aged B/nZVI/Pd was investigated, and the application
      of B/nZVI/Pd in wastewater indicated a removal efficiency higher than 93.75%.
      This provided a new environmental pollution management option for dyes
      contaminated sites.

PMID- 24140534
TI  - Sulfonated graphene oxide-ZnO-Ag photocatalyst for fast photodegradation and
      disinfection under visible light.
AB  - Synthesis of efficient visible-light-driven photocatalyst is urgent but
      challenging for environmental remediation. In this work, for the first time, the
      hierarchical plasmonic sulfonated graphene oxide-ZnO-Ag (SGO-ZnO-Ag) composites
      were prepared through nanocrystal-seed-directed hydrothermal method combining
      with polyol-reduction process. The results indicated that SGO-ZnO-Ag exhibited
      much faster rate in photodegradation of Rhodamine B (RhB) and disinfection of
      Escherichia coli (E. coli), than ZnO, SGO-ZnO and ZnO-Ag. SGO-ZnO-Ag totally
      degraded RhB dye and kill 99% of E. coli within 20 min under visible light
      irradiation. The outstanding performances of SGO-ZnO-Ag were attributed to the
      synergetic merits of SGO sheets, ZnO nanorod arrays and Ag nanoparticles.
      Firstly, the light absorption ability of SGO-ZnO-Ag composite in the visible
      region was enhanced due to the surface plasmon resonance of Ag. In addition, the
      hierarchical structure of SGO-ZnO-Ag composite improved the incident light
      scattering and reflection. Furthermore, SGO sheets facilitated charge transfer
      and reduce electron-hole recombination rate. Finally, the tentative mechanism was
      proposed and verified by the photoluminescence (PL) measurement as well as the
      theoretical finite-difference time-domain (FDTD) simulation. In view of above,
      this work paves the way for preparation of multi-component plasmonic composites
      and highlights the potential applications of SGO-ZnO-Ag in photocatalytic
      wastewater treatment field.

PMID- 24140535
TI  - CoFe2O4 magnetic nanoparticles as a highly active heterogeneous catalyst of oxone
      for the degradation of diclofenac in water.
AB  - A magnetic nanoscaled catalyst cobalt ferrite (CoFe2O4) was successfully prepared
      and used for the activation of oxone to generate sulfate radicals for the
      degradation of diclofenac. The catalyst was characterized by transmission
      electron microscopy, X-ray diffractometry, Fourier transform infrared
      spectroscopy and vibrating sample magnetometer. The effects of calcination
      temperature, initial pH, catalyst and oxone dosage on the degradation efficiency
      were investigated. Results demonstrated that CoFe2O4-300 exhibited the best
      catalytic performance and almost complete removal of diclofenac was obtained in
      15 min. The degradation efficiency increased with initial pH decreasing in the pH
      range of 5-9. The increase of catalyst and oxone dosage both had the positive
      effect on the degradation of diclofenac. Moreover, CoFe2O4 could retain high
      degradation efficiency even after being reused for five cycles. Finally, the
      major diclofenac degradation intermediates were identified and the primary
      degradation pathways were proposed.

PMID- 24140536
TI  - Radiation-induced grafting of sweet sorghum stalk for copper(II) removal from
      aqueous solution.
AB  - The influence of main components (cellulose, hemicellulose and lignin) of the
      sweet sorghum stalk on radiation-induced grafting reaction and adsorption of
      copper from aqueous solution was investigated. Sweet sorghum stalk was grafted
      with acrylic acid induced by gamma-irradiation. The results showed that the
      grafted stalk contained 1.6 mmol/g carboxyl groups, and its maximal adsorption
      capacity was 13.32 mg/g. The cellulose, hemicellulose and lignin of the raw
      materials were confirmed to involve in grafting reaction through comparing the
      grafting yield and the structure of the grafted materials. Both the structure and
      the composition of the sweet sorghum stalk had influence on the grafting reaction
      and adsorption capacity. The adsorption capacity of the grafted sweet sorghum
      stalk increased about five times, and the adsorption isotherm of the grafted
      materials conformed to the Langmuir model. The main mechanism for copper
      adsorption involved in ion exchange.

PMID- 24140537
TI  - Bioprecipitation of uranium from alkaline waste solutions using recombinant
      Deinococcus radiodurans.
AB  - Bioremediation of uranium (U) from alkaline waste solutions remains inadequately
      explored. We engineered the phoK gene (encoding a novel alkaline phosphatase,
      PhoK) from Sphingomonas sp. for overexpression in the radioresistant bacterium
      Deinococcus radiodurans. The recombinant strain thus obtained (Deino-PhoK)
      exhibited remarkably high alkaline phosphatase activity as evidenced by
      zymographic and enzyme activity assays. Deino-PhoK cells could efficiently
      precipitate uranium over a wide range of input U concentrations. At low uranyl
      concentrations (1 mM), the strain precipitated >90% of uranium within 2h while a
      high loading capacity of around 10.7 g U/g of dry weight of cells was achieved at
      10 mM U concentration. Uranium bioprecipitation by Deino-PhoK cells was not
      affected in the presence of Cs and Sr, commonly present in intermediate and low
      level liquid radioactive waste, or after exposure to very high doses of ionizing
      radiation. Transmission electron micrographs revealed the extracellular nature of
      bioprecipitated U, while X-ray diffraction and fluorescence analysis identified
      the precipitated uranyl phosphate species as chernikovite. When immobilized into
      calcium alginate beads, Deino-PhoK cells efficiently removed uranium, which
      remained trapped in beads, thus accomplishing physical separation of precipitated
      uranyl phosphate from solutions. The data demonstrate superior ability of Deino
      PhoK, over earlier reported strains, in removal of uranium from alkaline
      solutions and its potential use in bioremediation of nuclear and other waste.

PMID- 24140538
TI  - Stereoselective uptake and distribution of the chiral neonicotinoid insecticide,
      Paichongding, in Chinese pak choi (Brassica campestris ssp. chinenesis).
AB  - Neonicotinoid chiral insecticidal Paichongding is a promising substitute for the
      widely used imidacloprid. Four stereoisomers of Paichongding, 5R,7R, 5S,7S, 5S,7R
      and 5R,7S, were employed in both foliage and roots of Chinese pak choi to
      investigate their stereoselective uptake and distribution in pak choi. Results
      showed that after foliar application, no stereoselective absorption into pak-choi
      plants was observed among the enantiomers. Total absorptions were 35.40% of the
      applied amount for 5R,7R, 36.66% for 5S,7S, 36.80% for 5S,7R and 38.20% for 5R,7S
      at 96 HAT. The translocation of the four absorbed stereoisomers within pak choi
      occurred both acropetally and basipetally and the transport of (14)C from
      enantiomers 5R,7R and 5S,7S were significantly higher than for 5R,7S and 5S,7R.
      Significant stereoselective translocation inside plants was observed between
      Paichongding epimers. Total root uptake reached 16.49-19.85% for 5R,7R and 5S,7S,
      and 24.57-28.82% for 5S,7R and 5R,7S at 144 HAT. Both enantioselective and
      diastereoselective root uptake into pak-choi occurred between the four
      stereoisomers. The 5R,7S and 5S,7R enantiomers were more readily uptaken by the
      roots than 5R,7R and 5S,7S and accumulated in the edible leaves. These results
      will help to develop an understanding of Paichongding using only the target
      active enantiomer of pesticides. 

PMID- 24140539
TI  - Laccase production optimization by response surface methodology with Aspergillus
      fumigatus AF1 in unique inexpensive medium and decolorization of different dyes
      with the crude enzyme or fungal pellets.
AB  - In the present study, alkaline pretreatment was applied for the enhanced laccase
      production from rice straw. Various process parameters including sodium hydroxide
      concentration, pH and fermentation temperature were optimized via response
      surface methodology (RSM) with a Box-Behnken design (BBD). Through regression
      analysis, it was found that laccase activity was well fitted by a quadratic
      polynomial equation (R(2)=0.998, Adj R(2)=0.995), and the fermentation
      temperature was the most significant factor influencing laccase activity. The
      optimized process conditions found were NaOH concentration of 0.39 mol L(-1), pH
      3.12 and temperature 25.43  degrees C, under which laccase activity reached
      142,198 +/- 3586 U L(-1). Further studies were carried out to probe different
      dyes decolorization ability of laccase produced by Aspergillus fumigatus, A.
      fumigatus pellets and whole fermentation broth (WFB) using sodium hydroxide
      pretreated rice straw as sole carbon source. Results showed that pure laccase
      demonstrate limited decolorization ability to all the studied dyes, while crude
      laccase, A. fumigatus pellets and WFB exhibit significant decolorization ability
      to all the studied dyes with WFB being the most excellent one. Effectiveness of
      degradation was confirmed by uv-vis and phytotoxicity studies, which indicated
      that A. fumigatus transformed the dyes into non-toxic metabolites.

PMID- 24140540
TI  - Common ragweed: a threat to environmental health in Europe.
AB  - Common or short ragweed (Ambrosia artemisiifolia L.) is an annual herb belonging
      to the Asteraceae family that was described by Carl Linnaeus in the 18th century.
      It is a noxious invasive species that is an important weed in agriculture and a
      source of highly allergenic pollen. The importance placed on A. artemisiifolia is
      reflected by the number of international projects that have now been launched by
      the European Commission and the increasing number of publications being produced
      on this topic. This review paper examines existing knowledge about ragweed
      ecology, distribution and flowering phenology and the environmental health risk
      that this noxious plant poses in Europe. The paper also examines control measures
      used in the fight against it and state of the art methods for modelling
      atmospheric concentrations of this important aeroallergen. Common ragweed is an
      environmental health threat, not only in its native North America but also in
      many parts of the world where it has been introduced. In Europe, where the plant
      has now become naturalised and frequently forms part of the flora, the threat
      posed by ragweed has been identified and steps are being taken to reduce further
      geographical expansion and limit increases in population densities of the plant
      in order to protect the allergic population. This is particularly important when
      one considers possible range shifts, changes in flowering phenology and increases
      in the amount of pollen and allergenic potency that could be brought about by
      changes in climate. 

PMID- 24140541
TI  - Small heat shock proteins are necessary for heart migration and laterality
      determination in zebrafish.
AB  - Small heat shock proteins (sHsps) regulate cellular functions not only under
      stress, but also during normal development, when they are expressed in organ
      specific patterns. Here we demonstrate that two small heat shock proteins
      expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the
      development of left-right asymmetry. In zebrafish, laterality is determined by
      the motility of cilia in Kupffer's vesicle (KV), where hspb7 is expressed;
      knockdown of hspb7 causes laterality defects by disrupting the motility of these
      cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0
      structure, while control embyros have a predominately 9+2 structure. Reduction of
      either hspb7 or hspb12 alters the expression pattern of genes that propagate the
      signals that establish left-right asymmetry: the nodal-related gene southpaw
      (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1
      and lefty2. Partial depletion of hspb7 causes concordant heart, brain and
      visceral laterality defects, indicating that loss of KV cilia motility leads to
      coordinated but randomized laterality. Reducing hspb12 leads to similar
      alterations in the expression of downstream laterality genes, but at a lower
      penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain
      and visceral laterality, suggesting that these two genes have partially redundant
      functions in the establishment of left-right asymmetry. In addition, both hspb7
      and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial
      layer, which supports the migration and fusion of mesodermal cardiac precursors.
      In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk,
      migration defects predominated, suggesting that the yolk expression of these
      genes rather than heart expression is responsible for the migration defects. 

PMID- 24140543
TI  - Polymer structure and antimicrobial activity of polyvinylpyrrolidone-based iodine
      nanofibers prepared with high-speed rotary spinning technique.
AB  - Poly(vinylpyrrolidone)/poly(vinylpyrrolidone-vinylacetate)/iodine nanofibers of
      different polymer ratios were successfully prepared by a high-speed rotary
      spinning technique. The obtained fiber mats were subjected to detailed
      morphological analysis using an optical and scanning electron microscope (SEM),
      while the supramolecular structure of the samples was analyzed by positron
      annihilation lifetime spectroscopy (PALS). The maximum dissolved iodine of the
      fiber samples was determined, and microbiological assay was carried out to test
      their effect on the bacterial growth. SEM images showed that the polymer fibers
      were linear, homogenous, and contained no beads. The PALS results, both the o
      positronium (o-Ps) lifetime values and distributions, revealed the changes of the
      free volume holes of fibers as a function of their composition and the presence
      of iodine. The micro- and macrostructural characterisation of polymer fiber mats
      enabled the selection of the required composition from the point of their
      applicability as a wound dressing. 

PMID- 24140542
TI  - Sfrp1 and Sfrp2 are not involved in Wnt/beta-catenin signal silencing during lens
      induction but are required for maintenance of Wnt/beta-catenin signaling in lens
      epithelial cells.
AB  - During eye lens development, regulation of Wnt/beta-catenin signaling is critical
      for two major processes: initially it must be silent in the lens placode for lens
      development to proceed, but subsequently it is required for maintenance of the
      lens epithelium. It is not known how these different phases of Wnt/beta-catenin
      activity/inactivity are regulated. Secreted frizzled related protein-2 (Sfrp2), a
      putative Wnt-Fz antagonist, is expressed in lens placode and in lens epithelial
      cells and has been put forward as a candidate for regional Wnt/beta-catenin
      pathway regulation. Here we show its closely-related isoform, Sfrp1, has a
      complimentary pattern of expression in the lens, being absent from the placode
      and epithelium but expressed in the fibers. As mice with single knockouts of
      Sfrp1 or Sfrp2 had no defects in lens formation, we examined lenses of Sfrp1 and
      Sfrp2 double knockout (DKO) mice and showed that they formed lens placode and
      subsequent lens structures. Consistent with this we did not observe ectopic
      TCF/Lef activity in lens placode of DKOs. This indicates that Sfrp1 and Sfrp2
      individually, or together, do not constitute the putative negative regulator that
      blocks Wnt/beta-catenin signaling during lens induction. In contrast, Sfrp1 and
      Sfrp2 appear to have a positive regulatory function because Wnt/beta-catenin
      signaling in lens epithelial cells was reduced in Sfrp1 and Sfrp2 DKO mice.
      Lenses that formed in DKO mice were smaller than controls and exhibited a
      deficient epithelium. Thus Sfrps play a role in lens development, at least in
      part, by regulating aspects of Wnt/beta-catenin signaling in lens epithelial
      cells. 

PMID- 24140544
TI  - Self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan
      graft-stearic acid conjugates for delivery of doxorubicin.
AB  - A novel polymer, i.e. galactosylated O-carboxymethyl chitosan-graft-stearic acid
      (Gal-OCMC-g-SA) was synthesized for liver targeting delivery of doxorubicin. The
      chemical structure was characterized by FT-IR, (1)H NMR and elemental analysis.
      Gal-OCMC-g-SA could self-assemble into nanoparticles with diameter of 160 nm by
      probe sonication in aqueous medium and exhibited a low critical aggregation
      concentration of 0.047 mg/mL. The DOX-loaded Gal-OCMC-g-SA (Gal-OCMC-g-SA/DOX)
      self-assembled nanoparticles were almost spherical in shape with an average
      diameter of less than 200 nm and zeta potential of around -10 mV. In vitro
      release revealed that the Gal-OCMC-g-SA/DOX nanoparticles exhibited a sustained
      and pH-dependent drug release manner. Furthermore, the hemolysis test
      demonstrated the good safety of Gal-OCMC-g-SA in blood-contacting applications.
      These results indicated that Gal-OCMC-g-SA/DOX nanoparticles were highly
      potential to be applied in cancer therapy.

PMID- 24140545
TI  - Further experimentation of inhaled; LANTUS, ACTRAPID and HUMULIN with todays'
      production systems.
AB  - BACKGROUND: Several aerosol production systems have been used for aerosol insulin
      production. However; since the first studies several new models of jet-nebulizers
      and ultrasound nebulizers have been introduced in the market. MATERIALS AND
      METHODS: Three different models of jet-nebulizers (different brands, same
      properties) and three different ultrasound nebulizers (different brands, same
      properties). Six residual cups (2 small <= 6 ml and 3 large <= 8 ml) were used
      for the jet-nebulizers. The ultrasound nebulizers were used with their facemasks
      or with their inlets which were included in the purchase package. RESULTS:
      Ultrasound nebulizers; LANTUS produces by far the lowest mean droplets (2.44)
      half the size of the other two drugs (4.43=4.97). GIMA nebulizer is the most
      efficient producing one third of the droplet size of SHIMED and one second of
      EASYNEB (2.06<3.15<6.62). Finally, the 4 ml loading concentration is more
      suitable for supporting the production of smaller droplets (3.65<4.24). Drugs and
      nebulizers act interactively yielding very large droplets when ACTRAPID and
      HUMULIN are administered in joint with SHIMED nebulizer (9.59=7.72). Jet
      nebulizers; HUMULIN again is the least preferred insulin since it hardly reaches
      the low but equal performance of others at the loading level of 6 ml. Residual
      cups E and B produce uniquely lower mean droplets at loading level 6.
      CONCLUSIONS: Ultrasound nebulizers; the best suggested combination should be
      LANTUS insulin, GIMA nebulizer administered at loading dose of 4 ml jet
      nebulizers. A global review can give the best combination: the lowest mean
      droplets are produced when the drugs LANTUS (mostly) and ACTRAPID are
      administered, applying the SUNMIST nebulizer in concert with residual cup B at
      loading levels of 6 ml.

PMID- 24140546
TI  - In vivo evaluation of poly-l-asparagine nanocapsules as carriers for anti-cancer
      drug delivery.
AB  - Here, we report the in vivo proof of-concept of a novel nanocarrier, poly-l
      asparagine (PASN) nanocapsules, as an anticancer targeted drug delivery system.
      The nanocapsules were loaded with the fluorescent marker DiD (1,1'-dioctadecyl
      3,3,3',3'-tetramethylindodicarbocyanine perchlorate) and also with the model drug
      docetaxel to evaluate the biodistribution and efficacy profiles in healthy and
      glioma-bearing mice, respectively. Regardless of their cargo, the nanocapsules
      presented a size close to 180 nm, a surface charge around -40 mV and an
      encapsulation efficiency of 75-90%. The biodistribution study in healthy mice
      showed that PASN nanocapsules led to a two- and three-fold increment in the mean
      residence time (MRT) and area under the curve (AUC) values, respectively,
      compared to those of a non-polymeric nanoemulsion. Finally, the efficacy/toxicity
      study indicated that the encapsulated drug was as efficacious as the commercial
      formulation (Taxotere((r))), with the additional advantage of being considerably
      less toxic. Overall, these results suggest the potential of PASN nanocapsules as
      drug nanocarriers in anticancer therapy.

PMID- 24140547
TI  - Urinary incontinence incidence: quantitative meta-analysis of factors that
      explain variation.
AB  - PURPOSE: We sought to explain variation in female age specific incidence rates
      for urinary incontinence using published, population based studies. MATERIALS AND
      METHODS: We performed an extensive MEDLINE(r) review of published, population
      based studies of the female urinary incontinence incidence rate from 1966 to 2011
      using a combination of symptom and epidemiological search terms. A total of 18
      reports described 17 unique incidence studies. We abstracted the features of each
      study (eg sample size, followup, etc) along with detailed data on 109 age
      specific incidence rates (ie new cases per 1,000 person-years). Because the
      Nurses' Health Study had unique demographics and was dominant in sample size,
      analyses were completed with and without this study. Weighted (ie square root of
      sample size) linear regression was used to determine factors (ie age, source
      population, race, frequency score, etc) explaining variance among age specific
      incidence rates. RESULTS: Age and case definition accounted for 60% of the
      variation in incidence rates among studies. The age specific incidence was less
      than 2/1,000 person-years before age 40 years and it increased thereafter. For a
      given age group incidence rates varied as much as sixfold across studies, a
      finding that was largely explained by variation in case definition. CONCLUSIONS:
      The case definition accounts for substantial variation in urinary incontinence
      incidence estimates. Developing standards for reporting would provide a
      foundation for policy guidance and understanding etiology. We recommend that
      quantitative frequency criteria (eg 2 times or more per month) be reported vs
      vague thresholds (eg sometimes or often).

PMID- 24140548
TI  - Long-term adherence to antimuscarinic therapy in everyday practice: a systematic
      review.
AB  - PURPOSE: Antimuscarinic drug treatment is known to have side effects and,
      consequently, poor adherence in therapeutic regimens. In this systematic review
      we study the long-term (greater than 6 months) adherence to antimuscarinic drugs
      in daily clinical practice, and identify factors contributing to poor adherence
      and persistence. MATERIALS AND METHODS: This systematic review was conducted
      according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines. A literature search was performed using PubMed(r) and
      EmbaseTM using synonyms for incontinence, overactive bladder and antimuscarinics
      combined with synonyms for medication adherence. We chose to include only
      pharmaceutical database studies (using prescription/insurance claim data) and
      patient self-report studies, using established pharmacoepidemiological parameters
      such as persistence rate and medication possession rate. RESULTS: A total of
      1,245 titles were screened, of which 102 abstracts were assessed. Fourteen
      studies were ultimately included, comprising 190,279 unique patients (mean age
      69.5 years). Regardless of which specific antimuscarinic drug is studied,
      persistence rates are usually poor. Considering all drugs together, median
      persistence rates were 12.0% to 39.4% (with an outlier of 75.5%) at 12 months,
      8.0% to 15.0% at 18 months and 6.0% to 12.0% at 24 months. At 36 months
      persistence rates ranged from 0.0% (darifenacin) to 16.0% (trospium). Mean
      reported medication possession rates were also low, with a mean of 0.37 at 12
      months. Risk factors for discontinuation were identified, with the most important
      being younger age group, use of oxybutynin and use of immediate release
      formulations. CONCLUSIONS: Improvement in adherence and persistence with
      antimuscarinic medication should be an important goal in the development of new
      drugs for overactive bladder and urinary incontinence.

PMID- 24140549
TI  - The synergistic effect of mizoribine and a direct renin inhibitor, aliskiren, on
      unilateral ureteral obstruction induced renal fibrosis in rats.
AB  - PURPOSE: Renal fibrosis, the major histopathological change in various renal
      disorders, is closely related to renal dysfunction. Unilateral ureteral
      obstruction is a well established model of experimental renal disease that
      results in tubulointerstitial fibrosis. Previous studies showed that aliskiren
      and mizoribine ameliorated unilateral ureteral obstruction induced renal
      fibrosis. However, to our knowledge the protective effect of combination therapy
      with aliskiren and mizoribine against renal fibrosis is unknown. We investigated
      the synergistic effects of aliskiren and mizoribine combination therapy on
      unilateral ureteral obstruction induced fibrosis in rats. MATERIALS AND METHODS:
      Male Sprague Dawley(r) rats underwent unilateral ureteral obstruction followed by
      aliskiren and/or mizoribine treatment. Kidney samples were fixed for
      histopathology and immunohistochemistry of myofibroblasts (alpha-SMA) and
      macrophages (ED-1). Real-time quantitative reverse transcription-polymerase chain
      reaction was performed to measure alpha-SMA, TGF-beta1, osteopontin, MCP-1 and
      renin expression. RESULTS: After unilateral ureteral obstruction the tubular
      dilatation, interstitial volume and alpha-SMA expression scores were
      significantly decreased by combination therapy compared with monotherapy with
      aliskiren or mizoribine. Combination therapy caused a significant decrease in the
      number of ED-1 positive cells and in TGF-beta1 gene expression compared with
      monotherapy with either drug (each p <0.05). Combination therapy also decreased
      OPN and MCP-1 gene expression (p <0.05). CONCLUSIONS: Aliskiren and mizoribine
      combination therapy provides increased renal protection against renal fibrosis
      and unilateral ureteral obstruction induced inflammation.

PMID- 24140550
TI  - Serum N-glycan alteration associated with renal cell carcinoma detected by high
      throughput glycan analysis.
AB  - PURPOSE: Biomarkers for the early detection and prediction of survival in
      patients with renal cell carcinoma have not been established. We developed what
      is to our knowledge a novel glycoblotting method that allows high throughput,
      comprehensive, quantitative analysis of glycans in human serum. In this study we
      identified alterations in serum N-glycans associated with renal cell carcinoma.
      MATERIALS AND METHODS: We performed a comprehensive N-glycan structural analysis
      of serum from 64 patients with renal cell carcinoma and 34 age matched, healthy
      volunteers using glycoblotting methods and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. The peak intensity of N
      glycan was analyzed using logistic regression analysis and ROCs were used to
      select candidate N-glycans. Candidate N-glycans with a statistically significant
      relationship to renal cell carcinoma or overall survival were independently
      evaluated using a Cox regression model to determine superiority compared to other
      conventional renal cell carcinoma biomarkers. RESULTS: We identified 56 types of
      N-glycans in serum from healthy volunteers and patients with renal cell
      carcinoma. Peaks 40 and 43 were significantly more intense in patients than in
      volunteers. Peak 19 intensity was significantly higher and peak 49 intensity was
      significantly lower in patients with renal cell carcinoma who survived for a
      longer period. Multivariate analysis revealed that peaks 19 and 49 were
      independent predictors of overall survival. CONCLUSIONS: Serum N-glycan analysis
      is a promising approach to discovering new biomarkers for renal cell carcinoma.
      Further study is warranted to validate our results.

PMID- 24140551
TI  - Inflammatory and tissue remodeling urinary biomarkers before and after mid
      urethral sling surgery for stress urinary incontinence.
AB  - PURPOSE: Urinary biomarkers were measured in women at baseline and 1 year after
      surgery for stress urinary incontinence, and associations with clinicodemographic
      covariates and outcomes were analyzed. MATERIALS AND METHODS: Preoperative and
      postoperative urine specimens from 150 women were assayed for inflammatory
      biomarkers (tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta,
      interleukin-6, interleukin-10, interleukin-12p70, interleukin-17 and nerve growth
      factor) and tissue remodeling biomarkers (collagenase activity, matrix
      metalloproteinases-1, 2, 9 and 13, and NTx [N-telopeptide cross-linked collagen],
      epidermal growth factor and heparin-binding epidermal growth factor-like growth
      factor). Paired t-tests were used to compare changes in biomarkers during 1 year
      (significance p <0.05). Linear regression models correlated baseline and changes
      in biomarker levels with covariates (significance p <= 0.001). Logistic
      regression models, controlling for age, were used to analyze associations of
      baseline and changes in biomarker levels with surgical failure (significance p
      <0.05). RESULTS: During 1 year interleukin-12p70 decreased (mean +/- SD 0.53 +/-
      1.4 to 0.28 +/- 0.62 pg/mg creatinine, p = 0.04) and nerve growth factor
      increased (0.034 +/- 0.046 to 0.044 +/- 0.060 pg/ml/mOsm, p = 0.03). Baseline NTx
      level per mg creatinine was positively associated with age and postmenopausal
      status (p = 0.001), and negatively associated with current estrogen use (p =
      0.0001). Baseline collagenase activity per mg creatinine was positively
      associated with age (p = 0.001). Epidermal growth factor per mOsm, NTx per mOsm
      and interferon-gamma per mOsm were negatively correlated with age, current
      estrogen use and UDI (Urogenital Distress Inventory)-irritative subscale score,
      respectively (p <= 0.001). Subjects with lower baseline NTx per mg creatinine
      were less likely to experience surgical failure (OR 0.49, 95% CI 0.26-0.93, p =
      0.03). Changes in biomarker levels were not associated with any covariates or
      surgical failure. CONCLUSIONS: Stress urinary incontinence surgery was
      significantly less likely to fail in women with lower baseline NTx levels.
      Studies are needed to validate NTx as a possible independent biomarker for stress
      urinary incontinence surgery outcomes.

PMID- 24140553
TI  - Silica nanoparticle uptake induces survival mechanism in A549 cells by the
      activation of autophagy but not apoptosis.
AB  - We report here an in vitro evaluation of silica nanoparticle uptake by lung
      epithelial cells (A549), the cytotoxic effect of the particles and we propose
      autophagy as possible survival strategy. The effect of surface charge, serum
      proteins and the influence of inhibitors on the uptake of 20 nm monodispersed
      nanoparticles with various functional groups are discussed. Uptake rate of the
      particles with various functional groups is demonstrated to be similar in the
      presence of serum proteins, while the uptake rate ranking is COOH>NH2>OH under
      serum free conditions. Our results suggest an actin-dependent, macropinocytotic
      uptake process that was also confirmed by scanning and transmission electron
      microscopy. In spite of the intensive active uptake, significant cytotoxic effect
      is detected only at relatively high concentrations (above 250 MUg/mL). Blebbing
      of the cell surface is observed already at 5h of exposure and is shown to be
      related to autophagy rather than apoptotic cell death. The A549 cells display
      elevated levels of autophagosomes, however they do not express typical apoptosis
      markers such as increased amount of active caspase-3 and release of mitochondrial
      cytochrome C. Based on these results, we propose here an autophagic activity and
      cross-talk between autophagic and apoptotic pathways as a mechanism allowing the
      survival of A549 cells under exposure to silica nanoparticles.

PMID- 24140552
TI  - Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).
AB  - Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate
      (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin
      permeation studies have shown large permeation differences. Our aims were to
      determine DEHP permeation parameters and assess extent of skin DEHP metabolism
      among workers highly exposed to these lipophilic, low volatile substances.
      Surgically removed skin from patients undergoing abdominoplasty was immediately
      dermatomed (800 MUm) and mounted on flow-through diffusion cells (1.77 cm(2))
      operating at 32 degrees C with cell culture media (aqueous solution) as the
      reservoir liquid. The cells were dosed either with neat DEHP or emulsified in
      aqueous solution (166 MUg/ml). Samples were analysed by HPLC-MS/MS. DEHP
      permeated human viable skin only as the metabolite MEHP (100%) after 8h of
      exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP
      applied to the skin hardly permeated skin while the aqueous solution readily
      permeated skin measured in both cases as concentration of MEHP in the receptor
      liquid. DEHP pass through human skin, detected as MEHP only when emulsified in
      aqueous solution, and to a far lesser degree when applied neat to the skin. Using
      results from older in vitro skin permeation studies with non-viable skin may
      underestimate skin exposures. Our results are in overall agreement with newer
      phthalate skin permeation studies.

PMID- 24140554
TI  - Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated
      detachment of cultured oral epithelial cells and immune responses.
AB  - Porphyromonas gingivalis is a major etiological agent of periodontal diseases and
      the outer membrane vesicles (OMVs) contain virulence factors such as LPS and
      gingipains. In this study, we investigated the potential role of the OMVs in host
      immune response and tissue destruction during P. gingivalis infection. Firstly,
      we found that sera from periodontitis patients had significantly stronger
      reactivity against an OMV-producing wild type strain than the isogenic OMV
      depleted strain. OMVs were found to be highly antigenic, as absorption of patient
      sera with OMVs greatly reduced reactivity with whole cells of P. gingivalis. LC
      MS/MS analysis of OMVs revealed multiple forms of gingipains and several
      gingipain-related proteins. Western blots of OMVs using patient sera revealed a
      conserved immunoreactive antigen profile resembling the profile of OMV antigens
      that were recognized by gingipain antiserum, suggesting a potential role of OMV
      associated gingipains in triggering antibody-mediated immune responses to P.
      gingivalis infection. When OMVs were added to a monolayer of an oral squamous
      epithelial cell line, OMVs caused cell detachment, which was inhibited by
      preincubating OMVs with anti-gingipain antiserum. These data suggest that
      gingipain-laden OMVs may contribute to tissue destruction in periodontal diseases
      by serving as a vehicle for the antigens and active proteases. 

PMID- 24140555
TI  - Haeme oxygenase activity protects the host against excessive cardiac inflammation
      during experimental Trypanosoma cruzi infection.
AB  - The infection with Trypanosoma cruzi induces a robust cardiac inflammation that
      plays a pathogenic role in the development of Chagas heart disease. In this
      study, we aimed at investigating the effects of Haem Oxygenase (HO) during
      experimental infection by T. cruzi in BALB/c and C57BL/6 mice. HO has recently
      emerged as a key factor modulating the immune response in diverse models of
      inflammatory diseases. In mice with two different genetic backgrounds, the
      pharmacologic inhibition of HO activity with zinc-protoporphyrin IX (ZnPPIX)
      induced enhanced myocarditis and reduced parasitaemia, which was accompanied by
      an amplified production of nitric oxide and increased influx of CD4(+), CD8(+)
      and IFN-gamma(+) cells to the myocardium in comparison with the control group.
      Conversely, treatment with haemin (an activator of HO) lead to a decreased number
      of intracardiac CD4(+) (but not CD8(+)) cells compared to the control group. The
      mechanism involved in these observations is a modulation of the induction of
      regulatory T cells, because the stimulation or inhibition of HO was parallelled
      by an enhanced or reduced frequency of regulatory T cells, respectively. Hence,
      HO may be involved in the regulation of heart tissue inflammation and could be a
      potential target in conceiving future therapeutic approaches for Chagas disease. 

PMID- 24140556
TI  - A bacterium's guide to orienteering in the intestinal lumen. Interview by Emma
      Louise Walton.

PMID- 24140557
TI  - Porphyromonas gingivalis modulates Pseudomonas aeruginosa-induced apoptosis of
      respiratory epithelial cells through the STAT3 signaling pathway.
AB  - Pseudomonas aeruginosa is an important opportunistic bacterial pathogen, causing
      infections of respiratory and other organ systems in immunocompromised hosts that
      may invade and proliferate in mucosal epithelial cells to induce apoptosis.
      Previous studies suggest that oral bacteria, especially gram-negative periodontal
      pathogens, may enhance P. aeruginosa invasion into respiratory epithelial cells
      to augment tissue destruction. In this study, we investigated the effect of the
      periodontopathogen Porphyromonas gingivalis on P. aeruginosa-induced epithelial
      cell apoptosis. P. gingivalis invasion transiently inhibited P. aeruginosa
      induced apoptosis in respiratory epithelial cells via the signal transducer and
      activator of transcription 3 (STAT3) signaling pathway. The activated STAT3 up
      regulated the downstream anti-apoptotic moleculars survivin and B-cell leukemia-2
      (bcl-2). This process was accompanied by down-regulation of pro-apoptosis
      molecular Bcl-2-associated death promoter (bad) and caspase-3 activity
      inhibition. In addition, the activation of the STAT3 pathway was affected by P.
      gingivalis in a dose-dependent manner. Finally, co-invasion of P. aeruginosa and
      P. gingivalis led to greater cell death compared with P. aeruginosa challenge
      alone. These results suggest that regulation of P. aeruginosa-induced apoptosis
      by P. gingivalis contributes to the pathogenesis of respiratory disease.
      Interference with this process may provide a potential therapeutic strategy for
      the treatment and prevention of respiratory disease. 

PMID- 24140558
TI  - A taxonomic study of Phlebotomus (Larroussius) perfiliewi s. l.
AB  - Phlebotomus (Larroussius) perfiliewi is one of the main vectors of Leishmania
      infantum in the Mediterranean basin and in Central Asia. Its taxonomic status
      remains doubtful. It usually includes three taxa of specific or subspecific
      value, depending on the authors: P. perfiliewiParrot, 1930 s. st. in North
      Africa, Western Europe and the Balkans, Crimea; Phlebotomus galilaeusTheodor,
      1958 in Israel/Palestine and Cyprus and Phlebotomus transcaucasicusPerfiliev,
      1937 in Caucasus and Central Asia. While the identification of the females of P.
      perfiliewi s. l. is relatively easy, based on the particular morphology of their
      spermathecal ducts, the specific identification of the females of Phlebotomus
      perfiliewi perfiliewi, Phlebotomus perfiliewi galilaeus and Phlebotomus
      perfiliewi transcaucasicus is impossible. The differentiation of males, based
      mainly on characters on aedeagus, is also difficult. The goal of the present
      study is to carry out a taxonomic update based on a morphological study of
      specimens coming from various populations from Asia, Europe and North Africa
      coupled with their molecular analysis. 

PMID- 24140559
TI  - Vertical transmission of hepatitis C virus: a tale of multiple outcomes.
AB  - Globally, hepatitis C virus (HCV) infection affects approximately 130 million
      people and 3 million new infections occur annually. HCV is also recognized as an
      important cause of chronic liver disease in children. The absence of proofreading
      properties of the HCV RNA polymerase leads to a highly error prone replication
      process, allowing HCV to escape host immune response. The adaptive nature of HCV
      evolution dictates the outcome of the disease in many ways. Here, we investigated
      the molecular evolution of HCV in three unrelated children who acquired chronic
      HCV infection as a result of mother-to-child transmission, two of whom were also
      coinfected with HIV-1. The persistence of discrete HCV variants and their
      population structure were assessed using median joining network and Bayesian
      approaches. While patterns of viral evolution clearly differed between subjects,
      immune system dysfunction related to HIV coinfection or persistent HCV
      seronegativity stand as potential mechanisms to explain the lack of molecular
      evolution observed in these three cases. In contrast, treatment of HCV infection
      with PegIFN, which did not lead to sustained virologic responses in all 3 cases,
      was not associated with commensurate variations in the complexity of the variant
      spectrum. Finally, the differences in the degree of divergence suggest that the
      mode of transmission of the virus was not the main factor driving viral
      evolution. 

PMID- 24140560
TI  - Isolation and genomic characterization of a classical Muscovy duck reovirus
      isolated in Zhejiang, China.
AB  - A classical Muscovy reovirus was isolated from a sick Muscovy duck with white
      necrotic foci in its liver in Zhejiang, China, in 2000. This classical reovirus
      was propagated in a chicken fibroblast cell line (DF-1) with obvious cytopathic
      effects. Its genome was 22,967 bp in length, with approximately 51.41% G+C
      content and 10 dsRNA segments encoding 11 proteins, which formed a 3/3/4
      electrophoretic PAGE profile pattern. The length of the genomic segments was
      similar to those of avian orthoreoviruses (ARV and N-MDRV), ranging from 3959 nt
      (L1) to 1191nt (S4). All of the segments have the conserved terminal sequences 5'
      GCUUUU--UUCAUC-3', and with the exception of the S4 segment, all the genome
      segments apparently encode one single primary translation product. The genome
      analysis revealed that the S4 segment of classical MDRV is a bicistronic gene,
      encoding the overlapping ORFs for p10 and sigmaC but distinct from ARV and N
      MDRV/N-GRV, which codes for p10, p18 and sigmaC via the tricistronic S1 segment.
      A comparative sequence analysis provided evidence indicating extensive sequence
      divergence between classical MDRV and other avian orthoreoviruses. A phylogenetic
      analysis based on the RNA-dependent RNA polymerase (RdRp) and the major outer
      capsid proteins sigmaC was performed. Members of the DRVs in the Avian
      orthoreovirus species were clustered into two genetic groups (classical MDRV and
      N-MDRV genotype), and the classical MDRV isolates formed distinct lineages (China
      and Europe lineages), suggesting that the classical MDRVs isolated in restricted
      geographical region are evolving by different and independent pathways.

PMID- 24140561
TI  - Current status of zirconia restoration.
AB  - During the past decade, zirconia-based ceramics have been successfully introduced
      into the clinic to fabricate fixed dental prostheses (FDPs), along with a dental
      computer-aided/computer-aided manufacturing (CAD/CAM) system. In this article (1)
      development of dental ceramics, (2) the current status of dental CAD/CAM systems,
      (3) CAD/CAM and zirconia restoration, (4) bond between zirconia and veneering
      ceramics, (5) bond of zirconia with resin-based luting agents, (6) surface finish
      of zirconia restoration and antagonist enamel wear, and (7) clinical evaluation
      of zirconia restoration are reviewed. Yttria partially stabilized tetragonal
      zirconia polycrystalline (Y-TZP) showed better mechanical properties and superior
      resistance to fracture than other conventional dental ceramics. Furthermore,
      ceria-stabilized tetragonal zirconia polycrystalline and alumina nanocomposites
      (Ce-TZP/A) had the highest fracture toughness and had resistance to low
      temperature aging degradation. Both zirconia-based ceramics have been clinically
      available as an alternative to the metal framework for fixed dental prostheses
      (FDPs). Marginal adaptation of zirconia-based FDPs is acceptable for clinical
      application. The most frequent clinical complication with zirconia-based FDPs was
      chipping of the veneering porcelain that was affected by many factors. The
      mechanism for the bonding between zirconia and veneering ceramics remains
      unknown. There was no clear evidence of chemical bonding and the bond strength
      between zirconia and porcelain was lower than that between metal and porcelain.
      There were two alternatives proposed that might avoid chipping of veneering
      porcelains. One was hybrid-structured FDPs comprising CAD/CAM-fabricated
      porcelain parts adhering to a CAD/CAM fabricated zirconia framework. Another
      option was full-contour zirconia FDPs using high translucent zirconia. Combined
      application of silica coating and/or silane coupler, and 10-methacryloyloxydecyl
      dihydrogen phosphate is currently one of the most reliable bonding systems for
      zirconia. Adhesive treatments could be applied to luting the restorations and
      fabricating hybrid-structured FDPs. Full-contour zirconia FDPs caused concern
      about the wear of antagonist enamel, because the hardness of Y-TZP was over
      double that of porcelain. However, this review demonstrates that highly polished
      zirconia yielded lower antagonist wear compared with porcelains. Polishing of
      zirconia is possible, but glazing is not recommended for the surface finish of
      zirconia. Clinical data since 2010 are included in this review. The zirconia
      frameworks rarely got damaged in many cases and complications often occurred in
      the veneering ceramic materials. Further clinical studies with larger sample
      sizes and longer follow-up periods are required to investigate the possible
      influencing factors of technical failures. 

PMID- 24140562
TI  - Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the
      rat model of Parkinson's disease.
AB  - The subthalamic nucleus (STN) receives direct dopaminergic innervation from the
      substantia nigra pars compacta that degenerates in Parkinson's disease. The
      present study aimed to investigate the role of dopaminergic denervation of STN in
      the origin of levodopa-induced dyskinesias. Rats were distributed in four groups
      which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in
      the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB
      sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN
      lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with
      15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal
      involuntary movements were measured. In situ hybridization was performed
      measuring the expression of striatal preproenkephalin, preprodynorphin, STN
      cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not
      induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial
      (p<0.05), limb (p<0.05) and orolingual (p<0.01) dyskinesias in rats with a
      concomitant lesion of the nigrostriatal pathway. The attenuation of dyskinesias
      was associated with a decrease in the ipsilateral STN CO mRNA levels (p<0.05). No
      significant differences between MFB-lesion plus STN-sham and MFB-lesion plus STN
      lesion groups in the extent of STN dopaminergic denervation were observed.
      Moreover, intrasubthalamic microinfusion of dopamine in the MFB-lesion plus STN
      lesion group triggered orolingual (p<0.01), but not axial or limb, dyskinesias.
      These results suggest that dopaminergic STN innervation influences the expression
      of levodopa-induced dyskinesias but also the existence of non dopaminergic
      mediated mechanisms. STN noradrenergic depletion induced by 6-OHDA in the STN
      needs to be taken in account as a possible mechanism explaining the attenuation
      of dyskinesias in the combined lesion group. 

PMID- 24140563
TI  - Behavioral analyses of visually impaired Crx knockout mice revealed sensory
      compensation in exploratory activities on elevated platforms.
AB  - Visual perception is important for acquiring spatial information in many animals,
      and loss of vision often causes devastating effects on their survival. However,
      it may be compensated to some extent by utilizing other intact sensory
      modalities. The cone-rod homeobox (Crx) gene plays a key role in development of
      photoreceptor cells, but behavioral consequences of the gene deletion have not
      been well characterized. In this study, we analyzed homozygous knockout (Crx(-/
      )) mice by comparing with heterozygous knockout (Crx(+/-)) mice as controls. We
      first checked their vision with three different behavioral paradigms of the glass
      table visual recognition test, the light-dark transition test, and the Barnes
      maze test with a visual cue, all of which indicated that Crx(-/-) mice were blind
      while Crx(+/-) mice were sighted. In the fear conditioning test, Crx(-/-) mice
      were able to acquire both contextual and cued memory using non-visual
      information. Crx(-/-) mice showed normal thigmotaxis, but the exploratory
      activities were significantly increased. In the elevated plus maze test, it was
      unexpected that Crx(-/-) mice rarely fell down from the narrow platform. There
      was no reduction in their moving speeds and the moving distance was rather
      increased in Crx(-/-) mice. Such behaviors were not affected by trimming their
      whiskers. However, attachment of earplugs significantly reduced their exploratory
      activities. In summary, these data suggest that Crx(-/-) mice were behaviorally
      blind but were able to learn and recognize external environment utilizing non
      visual information, as exemplified by sensory compensation in exploratory
      activities on elevated platforms. 

PMID- 24140564
TI  - Modest elevation of corticosterone in preweanling rats impairs subsequent trace
      eyeblink conditioning during the juvenile period.
AB  - The hippocampus is known to be especially sensitive to the deleterious effects of
      glucocorticoids. Previously, we administered exogenous corticosterone, the major
      stress-related glucocorticoid in rats, to young developing rats using
      subcutaneous pellets which produced high pharmacological levels of circulating
      corticosterone as well as a sex-specific learning deficit for males on a
      hippocampus-mediated associative learning task, trace eyeblink conditioning [1].
      The present study evaluated the effects of corticosterone administered at a
      physiologically-relevant level by a more consistent release method, osmotic mini
      pumps. Pumps were implanted subcutaneously in 15-day-old rats to deliver either
      corticosterone or the vehicle control (PEG) at a rate of 1 MUl/h over 3 days. On
      Day 28, learning was assessed using trace eyeblink conditioning. The results of
      the present experiment revealed that a small elevation in corticosterone (11.77
      MUg/dl versus 6.02 MUg/dl for controls) within the normal physiological range
      impaired learning as determined by a significantly lower percentage and amplitude
      of total conditioned responses (CRs) and lower amplitude of adaptive responses
      relative to the control group. There were no significant differences in response
      timing, although the corticosterone group tended to produce CRs which began and
      peaked a little later than controls. These findings indicate that even modest
      elevations of corticosterone for several days can produce later impairments on
      this hippocampally mediated learning task.

PMID- 24140565
TI  - Tripchlorolide improves age-associated cognitive deficits by reversing
      hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8
      mice.
AB  - Deficits in cognition and performance accompanying age-related neurodegenerative
      diseases such as Alzheimer's disease (AD) are closely associated with the
      impairment of synaptic plasticity. Here, using a mouse model of senescence
      accelerated P8 (SAMP8), we reported the role of tripchlorolide (T4), an extract
      of the natural herb Tripterygium wilfordii Hook F, in improving cognitive
      deficits and promoting the long-term potentiation (LTP) of hippocampal slices via
      the N-methyl-D-aspartate receptor (NMDAR)-dependent signaling pathway. Our
      results demonstrated that chronic administration of T4 at low doses (0.25, 1.0,
      or 4.0 MUg/kg per day, injected intraperitoneally for 75 days) significantly
      improved learning and memory function in aged SAMP8 mice, as indicated by a chain
      of behavioral tests including the Y-maze and Morris water maze. Additionally, T4
      reversed the impaired LTP in hippocampal CA1 regions of SAMP8 mice in a dose
      dependent manner. Moreover, it upregulated the levels of phospho-NMDAR1,
      postsynaptic density-95 (PSD-95), phospho-calcium-calmodulin dependent kinase II
      (CaMKII), phospho-CREB and brain derived neurotrophic factor (BDNF) in the
      hippocampus. This indicates that T4 prevents the impairment of NMDAR-mediated
      synaptic plasticity-related signal molecules. At optimal doses, T4 did not show
      significant side-effects on blood counts, blood biochemical measures, or survival
      of the mice. This novel mechanism in reversing age-related synaptic dysfunction
      and NMDAR functional deficits suggests that T4 can halt the manifestation of a
      key early-stage event in AD. With the consideration of SAMP8 mice as a model to
      develop therapeutic interventions for AD, our findings provide new insight into
      the clinical application of tripchlorolide in AD treatment.

PMID- 24140566
TI  - Telephone versus internet administration of self-report measures of social
      anxiety, depressive symptoms, and insomnia: psychometric evaluation of a method
      to reduce the impact of missing data.
AB  - BACKGROUND: Internet-administered self-report measures of social anxiety,
      depressive symptoms, and sleep difficulties are widely used in clinical trials
      and in clinical routine care, but data loss is a common problem that could render
      skewed estimates of symptom levels and treatment effects. One way of reducing the
      negative impact of missing data could be to use telephone administration of self
      report measures as a means to complete the data missing from the online data
      collection. OBJECTIVE: The aim of the study was to compare the convergence of
      telephone and Internet administration of self-report measures of social anxiety,
      depressive symptoms, and sleep difficulties. METHODS: The Liebowitz Social
      Anxiety Scale-Self-Report (LSAS-SR), Montgomery-Asberg Depression Rating Scale
      Self-Rated (MADRS-S), and the Insomnia Severity Index (ISI) were administered
      over the telephone and via the Internet to a clinical sample (N=82) of
      psychiatric patients at a clinic specializing in Internet-delivered treatment.
      Shortened versions of the LSAS-SR and the ISI were used when administered via
      telephone. RESULTS: As predicted, the results showed that the estimates produced
      by the two administration formats were highly correlated (r=.82-.91; P<.001) and
      internal consistencies were high in both administration formats (telephone:
      Cronbach alpha=.76-.86 and Internet: Cronbach alpha=.79-.93). The correlation
      coefficients were similar across questionnaires and the shorter versions of the
      questionnaires used in the telephone administration of the LSAS-SR and ISI
      performed in general equally well compared to when the full scale was used, as
      was the case with the MADRS-S. CONCLUSIONS: Telephone administration of self
      report questionnaires is a valid method that can be used to reduce data loss in
      routine psychiatric practice as well as in clinical trials, thereby contributing
      to more accurate symptom estimates.

PMID- 24140567
TI  - Solvent environments significantly affect the enzymatic function of Escherichia
      coli dihydrofolate reductase: comparison of wild-type protein and active-site
      mutant D27E.
AB  - To investigate the contribution of solvent environments to the enzymatic function
      of Escherichia coli dihydrofolate reductase (DHFR), the salt-, pH-, and pressure
      dependence of the enzymatic function of the wild-type protein were compared with
      those of the active-site mutant D27E in relation to their structure and
      stability. The salt concentration-dependence of enzymatic activity indicated that
      inorganic cations bound to and inhibited the activity of wild-type DHFR at
      neutral pH. The BaCl2 concentration-dependence of the (1)H-(15)N HSQC spectra of
      the wild-type DHFR-folate binary complex showed that the cation-binding site was
      located adjacent to the Met20 loop. The insensitivity of the D27E mutant to
      univalent cations, the decreased optimal pH for its enzymatic activity, and the
      increased Km and Kd values for its substrate dihydrofolate suggested that the
      substrate-binding cleft of the mutant was slightly opened to expose the active
      site side chain to the solvent. The marginally increased fluorescence intensity
      and decreased volume change due to unfolding of the mutant also supported this
      structural change or the modified cavity and hydration. Surprisingly, the
      enzymatic activity of the mutant increased with pressurization up to 250MPa
      together with negative activation volumes of -4.0 or -4.8mL/mol, depending on the
      solvent system, while that of the wild-type was decreased and had positive
      activation volumes of 6.1 or 7.7mL/mol. These results clearly indicate that the
      insertion of a single methylene at the active site could substantially change the
      enzymatic reaction mechanism of DHFR, and solvent environments play important
      roles in the function of this enzyme. 

PMID- 24140568
TI  - Chronic hypoxia alters mitochondrial composition in human macrophages.
AB  - Hypoxia inducible factors (HIFs) are important mediators of the cellular adaptive
      response during acute hypoxia. The role of HIF-1 and HIF-2 during prolonged
      periods of hypoxia, i.e. chronic hypoxia is less defined. Therefore, we used
      human THP-1 macrophages with a knockdown of either HIF-1alpha, HIF-2alpha, or
      both HIFalpha-subunits, incubated them for several days under hypoxia (1% O2),
      and analyzed responses to hypoxia using 2D-DIGE coupled to MS/MS-analysis.
      Chronic hypoxia was defined as a time point when the early but transient
      accumulation of HIFalpha-subunits and mRNA expression of classical HIF target
      genes returned towards basal levels, with a new steady state that was constant
      from 72h onwards. From roughly 800 spots, that were regulated comparing normoxia
      to chronic hypoxia, about 100 proteins were unambiguously assigned during MS/MS
      analysis. Interestingly, a number of glycolytic proteins were up-regulated, while
      a number of inner mitochondrial membrane proteins were down-regulated
      independently of HIF-1alpha or HIF-2alpha. Chronic hypoxic conditions depleted
      the mitochondrial mass by autophagy, which occurred independently of HIF
      proteins. Macrophages tolerate periods of chronic hypoxia very well and adaptive
      responses occur, at least in part, independently of HIF-1alpha and/or HIF-2alpha
      and comprise mitophagy as a pathway of particular importance. 

PMID- 24140569
TI  - Hypoxia-mimetic effects in the secretome of human preadipocytes and adipocytes.
AB  - White adipose tissue (WAT) regulates energy metabolism by secretion of proteins
      with endocrine and paracrine effects. Dysregulation of the secretome of obesity
      associated enlarged WAT may lead to obesity-related disorders. This can be caused
      by hypoxia as a result of poorly vascularized WAT. The effect of hypoxia on the
      secretome of human (pre)adipocytes is largely unknown. Therefore, we investigated
      the effect of CoCl2, a hypoxia mimetic, on the secretome of human SGBS
      (pre)adipocytes by a proteomics approach combined with bioinformatic analysis. In
      addition, regulation of protein secretion was examined by protein turnover
      experiments. As such, secretome changes were particularly associated with protein
      down-regulation and extracellular matrix protein dysregulation. The observed up
      regulation of collagens in adipocytes may be essential for cell survival while
      down-regulation of collagens in preadipocytes may indicate a disturbed
      differentiation process. These CoCl2-induced changes reflect WAT dysfunction that
      ultimately may lead to obesity-associated complications. In addition, 9 novel
      adipocyte secreted proteins were identified from which 6 were regulated by CoCl2.
      Mass spectrometry data have been deposited to the ProteomeXchange with identifier
      PXD000162. 

PMID- 24140570
TI  - Morphological and histological studies on freshwater prawn Macrobrachium
      rosenbergii (de man) irradiated with (60)Co gamma radiation.
AB  - This study was framed to investigate the (60)Co gamma radiation induced
      morphological and histological variations in freshwater prawn Macrobrachium
      rosenbergii. The LD50 value of (60)Co gamma irradiated M. rosenbergii observed
      (by probit analysis) at 30 Gy. Prawns were irradiated to four different dose
      levels (3 mGy, 30 mGy, 300 mGy and 3,000 mGy) using Theratron Phoenix TeleCobalt
      Unit [P-33] and one control group (without irradiation) maintained separately.
      Irradiated groups exhibited several morphological variations such as
      discoloration; damaged rostrum; opaque coloration in cephalothorax; black bands
      and dot formation in abdomen; deformed uropods and telson in tail regions when
      compared with control group. The Hepato Somatic Index reflected the severity of
      radiation on hepatopancreas. Histological variations in gills, hepatopancreas and
      muscles of irradiated groups were observed. In gills, structural changes such as
      swollen and fused lamellae, abnormal gill tips, hyperplasic, necrotic and clavate
      globate lamellae were observed in gamma irradiated prawns. Accumulation of
      hemocytes in hemocoelic space, interstitial sinuses filled with abnormal
      infiltrated hemocytes, the tubular epithelium with ruptured basal laminae,
      abnormal and coagulated lumen, necrotic tubules, thickened basal laminae, tissue
      debris, necrotic hepatocytes were observed in irradiated prawn hepatopancreas. In
      muscle, shrinkage of muscular fiber and necrotic musculature were observed in
      irradiated prawns. These structural alterations of the organs it is felt could
      affect the vital physiological functions such as respiration, osmotic and ionic
      regulation in gills and muscles; absorption, storage and secretion of the
      hepatopancreas which in turn could adversely affect the growth and survival of
      freshwater prawn M. rosenbergii.

PMID- 24140571
TI  - Suppressive effects of a novel CC chemokine receptor 4 antagonist on Th2 cell
      trafficking in ligand- and antigen-induced mouse models.
AB  - CC chemokine receptor 4 (CCR4) has been implicated as a preferential marker for T
      helper type 2 (Th2) cells, and is believed to be involved in the pathology of
      allergic diseases by controlling Th2 cell trafficking into inflamed tissues. The
      objective of the study was to characterize the pharmacological properties of
      E0001-163, a novel CCR4 antagonist. E0001-163 was tested in both in vitro
      chemotaxis assays as well as in vivo mouse models of CCR4 ligand-induced air
      pouch and antigen-induced airway inflammation by utilizing in vitro-polarized Th2
      cells. In vitro, E0001-163 inhibited migratory response of human Th2-polarized
      cells to CCL22, a CCR4 ligand, with an IC50 value of 11.9 nM. E0001-163
      significantly suppressed CCL22-induced Th2 cell trafficking into mouse air pouch
      in a dose-dependent manner at doses of 3 and 10mg/kg, suggesting that E0001-163
      has an inhibitory effect on CCR4-mediated T cell trafficking in vivo. In
      addition, E0001-163 partially decreased Th2 cell trafficking and the level of IL
      4 in the lungs in Th2-tansferred and ovalbumin (OVA)-challenged mice. T cell
      trafficking involves multiple chemokine receptors both in acute and chronic
      phases, and our findings suggest that CCR4, together with other chemokine
      receptors, may be involved in Th2 cell trafficking under disease conditions.

PMID- 24140573
TI  - Thoraco-abdominal motion/displacement does not affect dyspnea following exercise
      training in COPD patients.
AB  - PURPOSE: The interrelations among chest wall kinematics (displacement and
      configuration), ventilatory profile and dyspnea relief following cycle exercise
      training (EXT) have not been systematically evaluated in hyperinflated chronic
      obstructive pulmonary disease (COPD) patients. We hypothesize that a decrease in
      ventilation affects dyspnea relief, regardless of the changes in chest wall
      kinematics. METHODS: Fourteen patients were studied before and after 24-session
      exercise training program. We evaluated the volumes of chest wall and its
      compartments (rib cage, and abdomen) using optoelectronic plethysmography.
      RESULTS: At iso-time EXT (i) reduced ventilation, respiratory frequency and
      dyspnea (by Borg scale), mildly improved rib cage configuration, but left
      operational volumes unchanged; (ii) Borg was much smaller for any comparable
      inspiratory reserve volume (IRVcw), and a decrease in IRVcw was tolerated much
      better for any given Borg. CONCLUSIONS: Regardless of the changes in chest wall
      kinematics, a decrease in ventilation attenuates dyspnea following EXT.

PMID- 24140572
TI  - Fenofibrate A peroxisome proliferator activated receptor-alpha agonist treatment
      ameliorates Concanavalin A-induced hepatitis in rats.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is physiologically
      highly expressed by hepatocytes, where it plays a pivotal anti-inflammatory and
      metabolic role. The decrease expression and functional activity of PPARalpha in
      hepatocytes during hepatitis C virus infection may contribute to the pathogenesis
      of the disease in humans. This study aims at evaluating the effects of PPARalpha
      activation with fenofibrate (FF) on liver inflammation, fibrosis and portal
      pressure (PP) in Concanavalin A (Con A)- induced hepatitis in rats. The rats were
      randomly divided to 3 groups; control (1 ml saline iv/wk) group, Con A
      (20mg/kg/iv/wk) group and Con A with FF (100mg/kg/day p.o) group. Blood samples
      and livers were collected by the end of the first, second, fourth and eighth
      injections of Con A for biochemical, histopathological and immunohistochemistry
      studies for alpha-smooth muscle actin (alpha SMA). Measurement of PP was
      performed by the end of the 8th week. FF group had a significant (P<0.05)
      decrease of serum alanine and aspartate aminotransferases with significant
      reduction of hepatic tumor necrosis factor alpha and malondialdehyde levels than
      Con A group. Histopathological examination revealed that treatment with FF
      significantly suppressed early inflammation, reduced alpha SMA, and apoptosis of
      hepatocytes induced by Con A, thereby preventing the progression of chronic liver
      injury and fibrosis. In addition FF group had a significantly lower PP (-89.0%)
      than Con A group. In conclusion PPARalpha activation significantly reduced liver
      inflammation, fibrosis and PP in Con A model of hepatitis that may represent a
      new therapeutic strategy for hepatitis and its complications.

PMID- 24140574
TI  - Interference of ferric ions with ferrous iron quantification using the ferrozine
      assay.
AB  - The ferrozine assay is a widely used colorimetric method for determining soluble
      iron concentrations. We provide evidence for a heretofore unrecognized
      interference of ferric ions (Fe(3+)) on ferrous iron (Fe(2+)) measurements
      performed in the dark. Fe(3+) concentrations affected the absorbance
      measurements, which linearly increased with incubation time. 

PMID- 24140575
TI  - Macroscale versus microscale methods for physiological analysis of biofilms
      formed in 96-well microtiter plates.
AB  - Microtiter plates with 96 wells have become one of the preferred platforms for
      biofilm studies mainly because they enable high-throughput assays. In this work,
      macroscale and microscale methods were used to study the impact of hydrodynamic
      conditions on the physiology and location of Escherichia coli JM109(DE3) biofilms
      formed in microtiter plates. Biofilms were formed in shaking and static
      conditions, and two macroscale parameters were assayed: the total amount of
      biofilm was measured by the crystal violet assay and the metabolic activity was
      determined by the resazurin assay. From the macroscale point of view, there were
      no statistically significant differences between the biofilms formed in static
      and shaking conditions. However, at a microscale level, the differences between
      both conditions were revealed using scanning electron microscopy (SEM). It was
      observed that biofilm morphology and spatial distribution along the wall were
      different in these conditions. Simulation of the hydrodynamic conditions inside
      the wells at a microscale was performed by computational fluid dynamics (CFD).
      These simulations showed that the shear strain rate was unevenly distributed on
      the walls during shaking conditions and that regions of higher shear strain rate
      were obtained closer to the air/liquid interface. Additionally, it was shown that
      wall regions subjected to higher shear strain rates were associated with the
      formation of biofilms containing cells of smaller size. Conversely, regions with
      lower shear strain rate were prone to have a more uniform spatial distribution of
      adhered cells of larger size. The results presented on this work highlight the
      wealth of information that may be gathered by complementing macroscale approaches
      with a microscale analysis of the experiments. 

PMID- 24140576
TI  - A multiplex bead-based suspension array assay for interrogation of
      phylogenetically informative single nucleotide polymorphisms for Bacillus
      anthracis.
AB  - Single nucleotide polymorphisms (SNPs) are abundant in genomes of all species and
      represent informative DNA markers extensively used to analyze phylogenetic
      relationships between strains. Medium to high throughput, open methodologies able
      to test many SNPs in a minimum time are therefore in great need. By using the
      versatile Luminex(r) xTAG technology, we developed an efficient multiplexed SNP
      genotyping assay to score 13 phylogenetically informative SNPs within the genome
      of Bacillus anthracis. The Multiplex Oligonucleotide Ligation-PCR procedure (MOL
      PCR) described by Deshpande et al., 2010 has been modified and adapted for
      simultaneous interrogation of 13 biallelic canonical SNPs in a 13-plex assay.
      Changes made to the originally published method include the design of allele
      specific dual-priming-oligonucleotides (DPOs) as competing detection probes
      (MOLigo probes) and use of asymmetric PCR reaction for signal amplification and
      labeling of ligation products carrying SNP targets. These innovations
      significantly reduce cross-reactivity observed when initial MOLigo probes were
      used and enhance hybridization efficiency onto the microsphere array,
      respectively. When evaluated on 73 representative samples, the 13-plex assay
      yielded unambiguous SNP calls and lineage affiliation. Assay limit of detection
      was determined to be 2ng of genomic DNA. The reproducibility, robustness and easy
      of-use of the present method were validated by a small-scale proficiency testing
      performed between four European laboratories. While cost-effective compared to
      other singleplex methods, the present MOL-PCR method offers a high degree of
      flexibility and scalability. It can easily accommodate newly identified SNPs to
      increase resolving power to the canSNP typing of B. anthracis. 

PMID- 24140577
TI  - 16S rRNA PCR followed by restriction endonuclease digestion: a rapid approach for
      genus level identification of important enteric bacterial pathogens.
AB  - The study describes a rapid approach for detection of common enteric bacterial
      pathogens, which involves partial amplification of the 16S rRNA gene by PCR using
      a colony from selective medium followed by restriction enzyme (RE) digestion
      using the EcoRI, HindIII and SalI enzymes. On the basis of RE digestion analysis
      different genera namely, Escherichia, Salmonella, Shigella, Vibrio,
      Campylobacter, Arcobacter, Yesinia and Listeria were differentiated. 

PMID- 24140578
TI  - An optimized technique for rapid genome modifications of Bacillus subtilis.
AB  - The transformation efficiency of naturally competent Bacillus subtilis cells can
      be significantly increased using beta recombinase binding sequences, as revealed
      by the results of this study. Plasmids containing different variations of these
      so called six-site-marker-cassettes were investigated. Furthermore, an optimized
      protocol for knock-out or knock-in mutations combining the Cre-lox-system and the
      six-sites is presented, which can be used for multiple genome modifications of B.
      subtilis. 

PMID- 24140579
TI  - Auditory cortical axons contact commissural cells throughout the guinea pig
      inferior colliculus.
AB  - Projections from auditory cortex (AC) affect how cells in both inferior colliculi
      (IC) respond to acoustic stimuli. The large projection from the AC to the
      ipsilateral IC is usually credited with the effects in the ipsilateral IC. The
      circuitry underlying effects in the contralateral IC is less clear. The direct
      projection from the AC to the contralateral IC is relatively small. An unexplored
      possibility is that the large ipsilateral cortical projection contacts the
      substantial number of cells in the ipsilateral IC that project through the
      commissure to the contralateral IC. Apparent contacts between cortical boutons
      and commissural cells were identified in the left IC after injection of different
      fluorescent tracers into the left AC and the right IC. Commissural cells were
      labeled throughout the left IC, and many (23-34%) appeared to be contacted by
      cortical axons. In the central nucleus, both disc-shaped and stellate cells were
      contacted. Antibodies to glutamic acid decarboxylase (GAD) were used to identify
      GABAergic commissural cells. The majority (>86%) of labeled commissural cells
      were GAD-immunonegative. Despite low numbers of GAD-immunopositive commissural
      cells, some of these cells were contacted by cortical boutons. Nonetheless, most
      cortically contacted commissural cells were GAD-immunonegative (i.e., presumably
      glutamatergic). We conclude that auditory cortical axons contact primarily
      excitatory commissural cells in the ipsilateral IC that project to the
      contralateral IC. These corticocollicular contacts occur in each subdivision of
      the ipsilateral IC, suggesting involvement of commissural cells throughout the
      IC. This pathway - from AC to commissural cells in the ipsilateral IC - is a
      prime candidate for the excitatory effects of activation of the auditory cortex
      on responses in the contralateral IC. Overall this suggests that the auditory
      corticofugal pathway is integrated with midbrain commissural connections. 

PMID- 24140581
TI  - The genetic landscape of anaplastic astrocytoma.
AB  - Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often
      occurs in middle aged patients. Clinically, it is challenging to distinguish A3
      from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape
      of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For
      comparison and to illuminate the genomic landscape of other glioma subtypes, we
      also included in our study diffuse astrocytoma WHO grade II (A2, n=7),
      oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade
      III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent
      mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In
      contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX
      mutations, and displayed a distinct spectrum of mutations. Finally, our study
      also identified novel genes that were not previously linked to this tumor type.
      In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, NOTCH4,
      NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of A3s. This
      study suggests genetic signatures will be useful for the classification of
      gliomas. 

PMID- 24140580
TI  - Neuron-specific chromatin remodeling: a missing link in epigenetic mechanisms
      underlying synaptic plasticity, memory, and intellectual disability disorders.
AB  - Long-term memory formation requires the coordinated regulation of gene
      expression. Until recently nucleosome remodeling, one of the major epigenetic
      mechanisms for controlling gene expression, had been largely unexplored in the
      field of neuroscience. Nucleosome remodeling is carried out by chromatin
      remodeling complexes (CRCs) that interact with DNA and histones to physically
      alter chromatin structure and ultimately regulate gene expression. Human exome
      sequencing and gene wide association studies have linked mutations in CRC
      subunits to intellectual disability disorders, autism spectrum disorder and
      schizophrenia. However, how mutations in CRC subunits were related to human
      cognitive disorders was unknown. There appears to be both developmental and adult
      specific roles for the neuron specific CRC nBAF (neuronal Brg1/hBrm Associated
      Factor). nBAF regulates gene expression required for dendritic arborization
      during development, and in the adult, contributes to long-term potentiation, a
      form of synaptic plasticity, and long-term memory. We propose that the nBAF
      complex is a novel epigenetic mechanism for regulating transcription required for
      long-lasting forms of synaptic plasticity and memory processes and that impaired
      nBAF function may result in human cognitive disorders.

PMID- 24140582
TI  - Gestational exposure to Byrsonima verbascifolia: teratogenicity, mutagenicity and
      immunomodulation evaluation in female Swiss mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Byrsonima verbascifolia is used in folk medicine
      to treat diarrhea, intestinal infections, chronic wounds, Chagas disease,
      inflammation and as a diuretic. However there is no investigation regarding the
      Byrsonima verbascifolia hydrometanolic extract (BVHME) used during gestation.
      MATERIALS AND METHODS: The pregnant females were randomly divided into 5 groups.
      Control group received saline plus DMSO (1%) in a volume of 0.1 mL/10 g (b.w.),
      via gavage, for at least 15 days prior to mating and throughout the gestational
      period. The Pre-treatment group received the BVHME, via gavage, at a dose of 50
      mg/kg (b.w.) for at least 15 days prior to mating and up to the appearance of the
      vaginal plug. The Organogenesis group received the BVHME at a dose of 50 mg/kg
      (b.w.), via gavage, on the 5-15th gestational day. The Gestational group received
      the BVHME at a dose of 50 mg/kg (b.w.), via gavage, throughout the gestational
      period (from the 1st to the 18th day of pregnancy). The Pre+Gestational group
      received the BVHME at a dose of 50mg/kg (b.w.), via gavage, for at least 15 days
      prior to mating and up to throughout the gestational period. The clinical signals
      of maternal and fetuses toxicity were evaluated, as the mutagenicity and
      immunomodulation tests were performed. RESULTS AND CONCLUSIONS: The present
      investigation shows, for the first time, that the use of Byrsonima verbascifolia
      extract in pregnant Swiss mice, did not alter the female reproductive function,
      mutagenicity or immunostimulation as well as not interfere with embryofetal
      development at least in our experimental conditions.

PMID- 24140583
TI  - Bioavailability enhancement of osthole after oral administration of Bushen Yizhi
      prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits
      extract in comparison to pure osthole at different doses.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Yizhi prescription (BSYZ) is a traditional
      Chinese compound prescription, which is commonly used in China for treating
      ShenXu and hypophrenia based on traditional Chinese medicine and Alzheimer's
      Disease according to modern Chinese medicine. Cnidium monnieri (L.) Cusson fruits
      (CM) is treated as the main herb of BSYZ, and its main active ingredient Osthole
      (OST) is considered as one of the major active ingredients of BSYZ. Even though
      OST plays an important role in the BSYZ its bioavailability is poor. In order to
      investigate whether the bioavailability of OST was influenced by BSYZ and CM
      extract, the comparative evaluations on pharmacokinetics of OST after oral
      administration of pure OST at different doses, CM and BSYZ extract were studied.
      MATERIALS AND METHODS: 30 rats were randomly assigned to five groups and orally
      administered with pure OST at different doses (15, 75 and 150 mg/kg), CM (15
      mg/kg OST) and BSYZ (15 mg/kg OST) extract. At different predetermined time
      points after administration, the concentrations of OST in rat plasma were
      determined by using the HPLC-UV method, and main pharmacokinetic parameters were
      investigated. RESULTS: The results showed that the pharmacokinetic parameters of
      OST were significantly different (p<0.05) among the groups. The AUC(0->t), AUC(0
      >infinity) and Cmax of OST were significantly increased after oral administration
      of BSYZ extract, followed by CM extract, in comparison to pure osthole at
      different doses. CONCLUSIONS: This present study indicated that the
      bioavailability of pure OST after oral administration was extremely low and it
      was dramatically enhanced because of the synergistic effect of the traditional
      Chinese Bushen Yizhi prescription.

PMID- 24140584
TI  - In vitro and in vivo hepatoprotective effect of ganodermanontriol against t-BHP
      induced oxidative stress.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Fr.) Karst. (Ganodermataceae)
      is a mushroom which is used as a traditional remedy in the treatment of human
      diseases such as hepatitis, liver disorders, hypercholesterolemia, arthritis,
      bronchitis and tumorigenic diseases. This study targets the evaluation of
      hepatoprotective activity of ganodermanontriol, a sterol isolated from Ganoderma
      lucidum, and the investigation of its mechanism of action in Hepa1c1c7 and murine
      liver cells upon tert-butyl hydroperoxide (t-BHP)-induced inflammation. t-BHP was
      utilized to stimulate an anti-inflammatory reaction in the hepatic cell lines and
      murine hepatic tissue examined. Western blot and reverse transcription
      quantitative polymerase chain reaction (RT-PCR) were used to estimate the
      expression of ganodermanontriol (GDT)-induced proteins, including heme oxidase-1
      (HO-1) and mitogen-activated protein kinases (MAPKs) as well as the corresponding
      mRNA. Luciferase assays were conducted to evaluate the interaction between NF-E2
      related factor-2 (Nrf-2), the antioxidant response element (ARE), and the
      promoter region of the HO-1 gene and subsequent gene expression. Biochemical
      markers for hepatotoxicity were monitored to assess whether GDT protected the
      cells from the t-BHP-mediated oxidative stimuli. RESULTS: GDT induced HO-1
      expression via the activation of Nrf-2 nuclear translocation and the subsequent
      transcription of the HO-1 gene in vitro and in vivo, which seemed to be regulated
      by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p38 signaling
      pathways. GDT exhibited in vitro and in vivo hepatoprotective activity as
      determined by the lowered levels of hepatic enzymes and malondialdehydes and the
      elevated glutathione levels. CONCLUSIONS: This study validates the
      ethnopharmacological application of Ganoderma lucidum as a treatment for hepatic
      disorders. GDT induced in vitro and in vivo anti-inflammatory activity in t-BHP
      damaged hepatic cells through the expression of HO-1, and in which PI3K/Akt and
      p38 kinases are involved. Our study motivates further research in the exploration
      of potent hepatoprotective agents from Ganoderma lucidum.

PMID- 24140585
TI  - Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic
      dextrane sulfate sodium models of mice colitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate (Punica granatum L.; Lythraceae) has
      traditionally been used for the treatment of various inflammatory diseases,
      including ulcerative colitis (UC). Because its fruits and extracts are rich in
      ellagitannins, which release ellagic acid when hydrolyzed, consumption of
      pomegranate products is currently being widely promoted for their potential
      health effects, including the prevention of inflammatory diseases and cancer. To
      evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium
      (DSS)-induced acute and chronic experimental colitis in two different strains of
      mice and to elucidate its possible mechanisms of action. MATERIALS AND METHODS:
      In the acute UC model, female Balb/C mice were treated with DSS (5%) for seven
      days while concomitantly receiving a dietary supplement of ellagic acid (2%). In
      the chronic UC model, female C57BL/6 mice received four week-long cycles of DSS
      (1% and 2%) interspersed with week-long recovery periods along with a diet
      supplemented with ellagic acid (0.5%). RESULTS: In acute model of UC, ellagic
      acid ameliorated disease severity slightly as observed both macroscopically and
      through the profile of inflammatory mediators (IL-6, TNF-alpha, and IFN-gamma).
      In the chronic UC model, ellagic acid significantly inhibited the progression of
      the disease, reducing intestinal inflammation and decreasing histological scores.
      Moreover, mediators such as COX-2 and iNOS were downregulated and the signaling
      pathways p38 MAPK, NF-kappaB, and STAT3 were blocked. CONCLUSIONS: Our study
      reinforces the hypothetical use of ellagic acid as an anti-inflammatory
      complement to conventional UC treatment in chronic UC patients and could be
      considered in the dietary prevention of intestinal inflammation and related
      cancer development.

PMID- 24140586
TI  - Passiflora incarnata L.: ethnopharmacology, clinical application, safety and
      evaluation of clinical trials.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Passiflora incarnata Linnaeus comprises
      approximately 520 species belonging to the Passifloraceae family. The majority of
      these species are vines found in Central or South America, with rare occurrence
      in North America, Southeast Asia and Australia. The genus Passiflora incarnata
      has long been used in traditional herbal medicine for the treatment of insomnia
      and anxiety in Europe, and it has been used as a sedative tea in North America.
      Furthermore, this plant has been used for analgesic, anti-spasmodic, anti
      asthmatic, wormicidal and sedative purposes in Brazil; as a sedative and narcotic
      in Iraq; and for the treatment of disorders such as dysmenorrhoea, epilepsy,
      insomnia, neurosis and neuralgia in Turkey. In Poland, this plant has been used
      to treat hysteria and neurasthenia; in America, it has been used to treat
      diarrhoea, dysmenorrhoea, neuralgia, burns, haemorrhoids and insomnia. Passiflora
      incarnata L. has also been used to cure subjects affected by opiate dependence in
      India. This review aims to provide up-to-date information about the pharmacology,
      clinical efficacy and clinical safety of Passiflora incarnata L. based on the
      scientific literature. In particular, the methodological accuracy of clinical
      trials is analysed in accordance with current consolidated guidelines on
      reporting the clinical efficacy of herbal medicine, offering new insight into
      opportunities for future research and development. METHODS: A bibliographic
      investigation was performed by examining the available data on Passiflora
      incarnata L. from globally accepted scientific databases and search engines
      (Pubmed, Scopus and Web of Science, SciFinder and Google Scholar). We selected
      studies, case reports, and reviews addressing the pharmacology and safety of
      Passiflora incarnata. RESULTS: Although numerous Passiflora incarnata L.
      derivative products have been commercialised as alternative anxiolytic and
      sedative remedies based on their long tradition of use, their supposed efficacy
      does not appear to be adequately corroborated by the literature, with clinical
      studies often featuring inadequate methodologies and descriptions of the products
      under investigation. This medicinal plant has shown a wide spectrum of
      pharmacological activities in preclinical experiments, including anxiolytic,
      sedative, antitussive, antiasthmatic, and antidiabetic activities. The plant has
      a good safety profile. The clinical trials that we included in this review were
      designed to evaluate and in some cases confirm promising observations of
      preclinical pharmacological activity, and the methodological limits of these
      studies are characterised here. CONCLUSION: In conclusion, clinical studies on
      the effects of products containing herbal preparations based on Passiflora
      incarnata reveal crucial weaknesses such as poor details regarding the drug
      extract ratio, limited patient samples, no description of blinding and
      randomisation procedures, incorrect definition of placebo, and lack of intention
      to treat analysis. In conclusion, the results of this review suggest that new
      clinical trials should be conducted using a more rigorous methodology to assess
      the traditional putative efficacy of Passiflora incarnata L.

PMID- 24140587
TI  - Intestinal antispasmodic effects of Helichrysum italicum (Roth) Don ssp. italicum
      and chemical identification of the active ingredients.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the Mediterranean Area, the flowers of
      Helichrysum italicum ssp. italicum are a traditional remedy for the treatment of
      intestinal complaints and are used as herbal tea for curing digestive, stomachic
      and intestinal diseases. In order to find scientific evidence for the traditional
      utilization of this plant, the effect of an ethanolic extract of Helichrysum
      italicum was investigated by using in vivo and in vitro experimental models.
      Then, through bioassay-guided fractionation procedures, active component(s) were
      identified. MATERIAL AND METHODS: Contractility in vitro was evaluated by
      stimulating the isolated ileum, in an organ bath, with acetylcholine and barium
      chloride; motility in vivo was evaluated by measuring upper gastrointestinal
      transit, both in control mice and in mice with experimental intestinal
      inflammation induced by croton oil. Chromatographic separation techniques such as
      HPLC and silica gel columns have yielded the active principles of Helichrysum
      italicum. RESULTS: We found that the ethanolic extract of Helichrysum italicum
      ssp. italicum flowers elicited antispasmodic actions in the isolated mouse ileum
      and inhibited transit preferentially in the inflamed gut. A bioassay guided
      fractionation of the extract yielded the known compounds 12-acetoxytremetone (1)
      and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2).
      CONCLUSION: Present study supported the traditional use of Helichrysum italicum
      ssp. italicum flowers for intestinal complaints and through bioassay-guided
      fractionation procedures from the crude extract we showed that 12
      acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]
      ethanone (2) acted in a synergistic way to produce an intestinal antispasmodic
      effect.

PMID- 24140588
TI  - Study on the correlation between constituents detected in serum from Rhizoma
      Smilacis Glabrae and the reduction of uric acid levels in hyperuricemia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Smilacis Glabrae (RSG) has been used in
      the clinical treatment of gout and hyperuricemia in China for thousands of years.
      Modern pharmacological studies have shown that RSG exhibits hypouricemic effects
      because of its significant inhibitory effect on the activity of xanthine oxidase.
      MATERIALS AND METHODS: The Rhizoma Smilacis Glabrae extract (RSGE) at 1 mL/100g
      oral administration was demonstrated to possess in vivo potent hypouricemic
      effects in hyperuricemic rats pretreated with oxonic acid potassium salt (200
      mg/kg, 2 mL/kg). UPLC-MS was used to identify the constituents absorbed in the
      serum. In addition, a bivariate correlation analysis between the changes in the
      relative contents of the constituents from RSGE detected by HPLC and the serum
      uric acid levels in hyperuricemic rats at different points in time was used to
      calculate their correlation coefficients. RESULTS: A total of 14 constituents
      were observed in the RSGE-treated rat serum, and 11 of these were inferred. An
      RSGE constituent was considered correlated with the hypouricemic effects if its
      correlation coefficient was above 0.5. The results suggested that only seven of
      the constituents absorbed in the serum of the hyperuricemic rats were correlated
      with hypouricemic effects, namely, palmitic acid, 3'-O-methyltaxifolin
      glucuronide, 3'-O-methyiastilbin glucuronide, astilbin glucuronide, 5-O
      caffeoylshikimic acid glucuronide, resveratrol glucuronide, and
      dihydrokaempferol. CONCLUSION: These findings provide potent evidence for the
      study on RSG as a pharmacodynamic material basis and for developing RSG as a safe
      and promising natural drug to prevent hyperuricemia and gout instead of
      allopurinol.

PMID- 24140589
TI  - Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi)
      Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line
      and rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The whole plant of Fagonia schweinfurthii
      (Hadidi) Hadidi (Family: Zygophyllaceae) is used in variety of diseases including
      hepatic ailments in deserts and dry areas of India. AIM OF THE STUDY: To evaluate
      antioxidant and hepatoprotective activity of ethanolic extract from Fagonia
      schweinfurthii (Hadidi) Hadidi (FSEE) in carbon tetrachloride (CCl4) induced
      hepatotoxicity in HepG2 cell line and rats. MATERIALS AND METHODS: In vitro
      antioxidant activity was determined by DPPH, ABTS radicals and hydrogen peroxide
      methods. In vitro cytotoxicity and hepatoprotective potential of FSEE were
      evaluated using HepG2 cells. Based on the cytotoxicity assay, FSEE (50, 100, 200
      ug/ml) was assessed for hepatoprotective potential against CCl4 induced toxicity
      in HepG2 cell line by monitoring cell viability, aspartate aminotransferase
      (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH) leakage,
      lipid peroxidation (LPO) and glutathione level (GSH). Further, in vivo
      hepatoprotective activity of FSEE was evaluated against CCl4 induced
      hepatotoxicity in male Wistar albino rats. Rats were pre-treated with FSEE (200
      mg, 400 mg kg(-1) day(-1) p.o.) for 7 days followed by a single dose of CCl4 (1.0
      ml/kg, i.p.) on 8th day. Silymarin was used as positive control. After 24h of
      CCl4 administration, various biochemical parameters like aspartate
      aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase
      (ALP), total bilirubin (TB) and total protein (TP) levels were estimated in
      serum. The antioxidant parameters like superoxide dismutase (SOD) activity,
      catalase (CAT) activity, glutathione (GSH) content and malondialdehyde (MDA)
      level in the liver homogenate were determined. Histopathological changes in the
      liver of different groups were also studied. RESULTS: The FSEE possessed strong
      antioxidant activity in vitro. The results indicated that CCl4 treatment caused a
      significant decrease in cell viability. The CCl4-induced changes in the HepG2
      cells were significantly ameliorated by treatment of the FSEE. FSEE significantly
      prevented CCl4 induced elevation of AST, ALT, ALP, TB, and CCl4 induced decrease
      in total protein in rats. FSEE treated rat liver anti-oxidant parameters (SOD,
      CAT, MDA and GSH,) were significantly antagonized for the pro-oxidant effect of
      CCl4. Histopathological studies also supported the protective effect of FSEE.
      CONCLUSION: The results of this study revealed that FSEE has significant
      hepatoprotective activity. This effect may be due to the ability of the extract
      to inhibit lipid peroxidation and increase in the anti-oxidant enzymatic
      activity.

PMID- 24140590
TI  - Wound healing potential of a dimeric InlB variant analyzed by in vitro
      experiments on re-epithelialization of human skin models.
AB  - A constitutively dimeric truncated variant of internalin B (InlB321-CD), acting
      as stimulator of the receptor tyrosine kinase MET, was tested for dermal wound
      healing potential. Due to a lack of the endogenous MET agonist HGF/SF in chronic
      wounds, HGF/SF substitution by an InlB321-CD-loaded hydrogel might be beneficial
      in chronic wound therapy. In this study, InlB321-CD in solution and incorporated
      in a hydrogel was tested for mitogenic effects on immortalized human dermal
      keratinocytes (HaCaT) with an MTT assay. Cell migration was investigated with a
      scratch assay on primary keratinocytes (PHK) and on HaCaT. For the latter,
      scratching needed to be mitomycin C-controlled. InlB321-CD effects on a model of
      human skin were analyzed histologically with respect to viability. InlB321-CD led
      to dose-dependent proliferative effects on HaCaT cells whereas the equimolar dose
      of monomeric InlB321 did not. Upon hydrogel incorporation of InlB321-CD its
      mitogenic activity for HaCaT cells was maintained thus confirming the hydrogel as
      a promising drug delivery system. Motogenic effects were shown on both HaCaT and
      PHK cells. InlB321-CD neither possesses cytotoxic effects on the viability of a
      human skin model nor alters its organotypic cell morphology. 

PMID- 24140591
TI  - In vitro-in vivo extrapolation of drug-induced proarrhythmia predictions at the
      population level.
AB  - Drug cardiotoxicity is a serious issue for patients, regulators, pharmaceutical
      companies and health service payers because they are all affected by its
      consequences. Despite the wide range of data they generate, existing approaches
      for cardiac safety testing might not be adequate and sufficiently cost-effective,
      probably as a result of the complexity of the problem. For this reason,
      translational tools (based on biophysically detailed, mathematical models)
      allowing for in vitro-in vivo extrapolation are gaining increasing interest. This
      current review describes approaches that can be used for cardiac safety
      assessment at the population level, by accounting for various sources of
      variability including kinetics of the compound of interest. 

PMID- 24140592
TI  - Magnetic nanoparticles: a novel platform for cancer theranostics.
AB  - Multifunctional nanoplatforms represent a cutting edge tool in biomedical
      applications as a result of their applicability in the concurrent monitoring of
      medical treatment. Magnetic nanoparticles (MNPs) have generated great interest in
      the field of cancer nanotheranostics owing to their intrinsic magnetic property
      that enables them to be used as contrast agents in magnetic resonance imaging and
      as a therapeutic system in conjunction with hyperthermia. In addition, the
      physical properties and biocompatibility of MNPs help them to act as efficient
      drug carriers for targeted therapeutic regimes. In this review, we have discussed
      the different theranostic applications of MNPs. Further, we have raised the
      current challenges associated with the clinical translation of MNPs along with
      future opportunities in this field. 

PMID- 24140594
TI  - Distribution of decidual natural killer cells and macrophages in the
      neighbourhood of the trophoblast invasion front: a quantitative evaluation.
AB  - STUDY QUESTION: Do decidual natural killer (dNK) cells and decidual macrophages
      (dMph) become enriched in the vicinity of the trophoblast invasion front? SUMMARY
      ANSWER: Morphometric image analysis and areal cell density calculations, which
      excluded observer bias, showed an enrichment of decidual leukocytes in the
      neighbourhood of the trophoblast invasion front. WHAT IS KNOWN ALREADY: In
      previous studies, the number of decidual leukocytes was visually counted in
      medium- or high power fields. These methods, however, cannot reveal the exact
      spatial relationship between leukocytes and invasive trophoblast cells, and are
      therefore prone to subjective errors. Thus, a more objective approach is
      required. STUDY DESIGN, SIZE, DURATION: Applying a new method of morphometric
      image analysis, leukocyte populations were studied in human tissue fragments
      derived from first trimester placentation sites (n = 7) as well as in co-cultures
      of first trimester decidual tissue with placental villi of the same pregnancy
      representing an appropriate in vitro model of trophoblast invasion (n = 15).
      PARTICIPANTS/MATERIALS, SETTINGS, METHODS: First trimester decidual tissue was
      obtained from women undergoing elective terminations of pregnancy at 7-10 weeks
      of gestational age. Tissue sections were double-stained immunohistochemically for
      markers of dNK cells or dMph on one hand, and for invasive extravillous
      trophoblast cells on the other. To analyse the distribution of leukocytes,
      distinct cell compartments as well as cell neighbourhood areas were defined.
      Finally, relative areal cell densities were calculated and these data were
      compared with those of an in vitro model of trophoblast invasion as well as with
      tissue fragments derived from decidua parietalis without trophoblast cells. MAIN
      RESULTS AND THE ROLE OF CHANCE: At first trimester placentation sites, a higher
      density of dNK cells as well as of dMph was found in close proximity to the
      invasive trophoblast (P <= 0.01), compared with the average areal cell density of
      decidual leukocytes in the tissue with exclusion of the trophoblast. The highest
      areal cell density of leukocytes was determined up to a distance of 20 MUm from
      the trophoblast cells, whereas in more distant regions it was even lower than
      average, indicating a migration of these leukocytes towards the trophoblast
      invasion front. In the three-dimensional co-culture model, however, we found an
      enrichment of dMph (P <= 0.01) but not of dNK cells (P > 0,05) in the
      neighbourhood of the invasive trophoblast. LIMITATIONS, REASONS FOR CAUTION: The
      morphometric image analysis depends on intense immunohistochemical staining that
      is free of background and cross-reactivity. WIDER IMPLICATIONS OF THE FINDINGS:
      The presented method will be useful not only for the investigation of recurrent
      miscarriage but also in the fields of tumour immunology and inflammation. STUDY
      FUNDING/COMPETING INTEREST(S): The study was supported by the European Commission
      (Network of Excellence 'The Control of Embryo Implantation (EMBIC)', FP6-512040,
      lead researcher: P.S.), and by the Franz Lanyar Foundation of the Medical
      University of Graz, Austria (Grant #347). None of the authors declared a conflict
      of interests.

PMID- 24140593
TI  - BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in
      human granulosa cells.
AB  - In addition to somatic cell-derived growth factors, oocyte-derived growth
      differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play
      essential roles in female fertility. However, few studies have investigated their
      effects on human ovarian steroidogenesis, and fewer still have examined their
      differential effects or underlying molecular determinants. In the present study,
      we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor
      cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme
      expression and investigate potential mechanisms of action. In SVOG cells, neither
      GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or
      3beta-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9,
      significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and
      protein levels as well as progesterone production. These suppressive effects,
      along with the induction of Sma and Mad-related protein (SMAD)1/5/8
      phosphorylation, are attenuated by cotreatment with 2 different BMP type I
      receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin
      receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of
      BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of
      ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These
      results provide evidence that oocyte-derived BMP15 down-regulates StAR expression
      and decreases progesterone production in human granulosa cells, likely via ALK3
      mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a
      critical role in the regulation of progesterone to prevent premature
      luteinization during the late stage of follicle development. 

PMID- 24140595
TI  - Co-Creation With TickiT: Designing and Evaluating a Clinical eHealth Platform for
      Youth.
AB  - BACKGROUND: All youth are susceptible to mental health issues and engaging in
      risky behavior, and for youth with chronic health conditions, the consequences
      can be more significant than in their healthy peers. Standardized paper-based
      questionnaires are recommended by the American Academy of Pediatrics in community
      practice to screen for health risks. In hospitals, psychosocial screening is
      traditionally undertaken using the Home Education, Eating, Activities, Drugs,
      Depression, Sex, Safety (HEEADDSS) interview. However, time constraints and
      patient/provider discomfort reduce implementation. We report findings from an
      eHealth initiative undertaken to improve uptake of psychosocial screening among
      youth. OBJECTIVE: Youth are sophisticated "technology natives." Our objective was
      to leverage youth's comfort with technology, creating a youth-friendly
      interactive mobile eHealth psychosocial screening tool, TickiT. Patients enter
      data into the mobile application prior to a clinician visit. Response data is
      recorded in a report, which generates alerts for clinicians, shifting the
      clinical focus from collecting information to focused management. Design goals
      included improving the patient experience, improving efficiency through
      electronic patient based data entry, and supporting the collection of aggregated
      data for research. METHODS: This paper describes the iterative design and
      evaluation processes undertaken to develop TickiT including co-creation
      processes, and a pilot study utilizing mixed qualitative and quantitative
      methods. A collaborative industry/academic partnership engaged stakeholders
      (youth, health care providers, and administrators) in the co-creation development
      process. An independent descriptive study conducted in 2 Canadian pediatric
      teaching hospitals evaluated the feasibility of the platform in both inpatient
      and ambulatory clinical settings, evaluating both providers and patient responses
      to the platform. RESULTS: The independent pilot feasibility study included 80
      adolescents, 12-18 years, and 38 medical staff-residents, inpatient and
      outpatient pediatricians, and surgeons. Youth uptake was 99% (79/80), and survey
      completion 99% (78/79; 90 questions). Youth found it easy to understand (92%,
      72/78), easy to use (92%, 72/78), and efficient (80%, 63/79 with completion rate
      < 10 minutes). Residents were most positive about the application and surgeons
      were least positive. All inpatient providers obtained new patient information.
      CONCLUSIONS: Co-creative design methodology with stakeholders was effective for
      informing design and development processes to leverage effective eHealth
      opportunities. Continuing stakeholder engagement has further fostered platform
      development. The platform has the potential to meet IHI Triple Aim goals.
      Clinical adaptation requires planning, training, and support for health care
      providers to adjust their practices.

PMID- 24140596
TI  - Activity of chalcones derived from 2,4,5-trimethoxybenzaldehyde against
      Meloidogyne exigua and in silico interaction of one chalcone with a putative
      caffeic acid 3-O-methyltransferase from Meloidogyne incognita.
AB  - Meloidogyne exigua is a parasitic nematode of plants that causes great losses to
      coffee farmers. In an effort to develop parasitic controls, 154 chalcones were
      synthesized and screened for activity against this nematode. The best results
      were obtained with (2E)-1-(4'-nitrophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1
      one (6) with a 50% lethal concentration (LC50) of 171 MUg/ml against M. exigua
      second-stage juveniles, in comparison to the commercially-available nematicide
      carbofuran which had an LC50 of 260 MUg/ml under the same conditions. When coffee
      plants were used, 6 reduced the nematode population to ~50% of that observed in
      control plants. To investigate the mechanism of action of 6, an in silico study
      was carried out, which indicated that 6 may act against M. exigua through
      inhibition of a putative caffeic acid 3-O-methyltransferase homodimer, the amino
      acid sequence of which was determined by examining the genome of Meloidogyne
      incognita.

PMID- 24140597
TI  - Toxoplasma gondii infection: What is the real situation?
AB  - The prevalence of chronic Toxoplasma infections reported in the literature varies
      enormously. We hypothesize that one factor could be due to the different methods
      used in the evaluation of infections. Serological evidence of Toxoplasma
      infections in 450 pregnant women (PW) and 300 HIV-infected patients (HIV) were
      investigated by the Sabin-Feldman dye test and two other commercial ELISA kits
      (kit1 and kit2). Anti-Toxoplasma IgG antibodies obtained from the Sabin-Feldman
      dye test, ELISA kit1 and ELISA kit2 in the PW subjects were 14.7%, 29.6% and
      38.7%, and in the HIV subjects were 13%, 34.7% and 36.3%, respectively. So there
      were significant differences in the seroprevalences when different diagnostic
      tests were used (P<0.05). Regarding Sabin-Feldman dye test as the gold standard
      for anti-Toxoplasma antibodies detection, we found that the sensitivity and
      specificity of the ELISA kit1 and kit2 was in the range of their specification.
      However as the two ELISA kits used in our study identified a much higher
      prevalence of Toxoplasma infections which indicated that false positive cases
      were being reported. Based on results obtained, it is therefore highly
      recommended that research workers should be aware that the reports of serological
      studies in terms of high positive results should be treated with some skepticism
      until additional precise diagnostic tools are developed.

PMID- 24140598
TI  - The tyrosine phosphatase SHP-1 inhibits proliferation of activated hepatic
      stellate cells by impairing PDGF receptor signaling.
AB  - The dimerization and auto-transphosphorylation of platelet-derived growth factor
      receptor (PDGFR) upon engagement by platelet-derived growth factor (PDGF)
      activates signals promoting the mitogenic response of hepatic stellate cells
      (HSCs) due to liver injury, thus contributing to the development of hepatic
      fibrosis. We demonstrate that the tyrosine phosphatases Src homology 2 domain
      containing phosphatase 1 and 2 (SHP-1 and SHP-2) act as crucial regulators of a
      complex signaling network orchestrated by PDGFR activation in a spatio-temporal
      manner with diverse and opposing functions in HSCs. In fact, silencing of either
      phosphatase shows that SHP-2 is committed to PDGFR-mediated cell proliferation,
      whereas SHP-1 dephosphorylates PDGFR hence abrogating the downstream signaling
      pathways that result in HSC activation. In this regard, SHP-1 as an off-switch of
      PDGFR signaling appears to emerge as a valuable molecular target to trigger as to
      prevent HSC proliferation and the fibrogenic effects of HSC activation. We show
      that boswellic acid, a multitarget compound with potent anti-inflammatory action,
      exerts an anti-proliferative effect on HSCs, as in other cell models, by
      upregulating SHP-1 with subsequent dephosphorylation of PDGFR-beta and
      downregulation of PDGF-dependent signaling after PDGF stimulation. Moreover, the
      synergism resulting from the combined use of boswellic acid and imatinib, which
      directly inhibits PDGFR-beta activity, on activated HSCs offers new perspectives
      for the development of therapeutic strategies that could implement molecules
      affecting diverse players of this molecular circuit, thus paving the way to multi
      drug low-dose regimens for liver fibrosis. 

PMID- 24140599
TI  - Acidic properties of aqueous phosphoric acid solutions: a microscopic view.
AB  - We report on new neutron and x-ray diffraction data on D2O:D3PO4 solutions at two
      concentrations, 1:1 and 3:1. The experimental datasets were modelled
      simultaneously by the reverse Monte Carlo (RMC) method. From the resulting
      models, partial radial distribution functions (prdf) and coordination numbers
      were obtained. The acidity was found to decrease with increasing D3PO4
      concentration. The ratio of dissociated acidic protons was estimated by dedicated
      simulation runs using average coordination number constraints. It was found that
      in the saturated solution the ratio of dissociated protons cannot exceed 20%. 

PMID- 24140600
TI  - Expression screening of bacterial libraries of recombinant alpha-1 proteinase
      inhibitor variants for candidates with thrombin inhibitory capacity.
AB  - Exhaustive mutagenesis studies of the reactive centre loop (RCL), a key
      structural component of proteins belonging to the serpin superfamily of protease
      inhibitors, are complicated by the size of the RCL, serpin conformational
      complexity, and, for most serpins, the lack of a serpin-dependent phenotype of
      expressing cells. Here, we describe a thrombin capture assay that distinguished
      thrombin-inhibitory recombinant human alpha-1 proteinase inhibitor (API M358R)
      from non-inhibitory API variants in Escherichia coli lysates prepared from either
      single clones or pools. Binding of API proteins in the lysates to thrombin
      immobilized on microtiter plate wells was quantified via colour generated by a
      peroxidase-coupled anti-API antibody. Bacterial expression plasmids encoding
      inhibitory API M358R were mixed 1:99 with plasmids encoding non-inhibitory API
      T345R/M358R and the resulting library screened in pools of 10. All above
      background signals arising from pools or subsequently re-probed single clones
      were linked to the presence of plasmids encoding API M358R. Screening of a
      portion of another expression library encoding hypervariable API with all
      possibilities at codons 352-358 also yielded only novel, thrombin-inhibitory
      variants. Probing a smaller library expressing all possible codons at Ala347
      yielded the wild type, 6 different functional variants, one partially active
      variant, and two variants with no thrombin-inhibitory activity. API antigen
      levels varied considerably less among Ala347 variants than activity levels, and
      comparison of rate constants of inhibition of purified API variants to their
      corresponding thrombin capture assay lysate values was used to establish the
      sensitivity and specificity of the assay. The results indicate that the approach
      is sufficiently robust to correctly identify functional versus non-functional
      candidates in API expression libraries, and could be of value in systematically
      probing structure/function relationships not only in the API RCL, but also in
      that of other serpins. 

PMID- 24140601
TI  - Comparative characterization of direct and indirect substrate probes for on-chip
      transamidating activity assay of transglutaminases.
AB  - The development of molecular probes is a prerequisite for activity-based protein
      profiling. This strategy helps in characterizing the catalytic activity and
      function of proteins, and how these proteins and protein complexes control
      biological processes of interest. These probes are composed of a reactive
      functional group and a reporter tag. The reactive group of these substrate probes
      has been considered to be important to their design, while the significance of
      the reporter tag is relatively underestimated. In this study we compare TAMRA
      cadaverine and biotin-cadaverine, two substrate probes that have different
      reporter tags but an identical reactive functional group. We assess the on-chip
      transamidating activity of two transglutaminases; transglutaminase 2 and blood
      coagulation factor XIII. Activity assays were more easily executed when using the
      direct probe TAMRA-cadaverine. However the indirect probe, biotin-cadaverine,
      provided a wider dynamic range, higher signal-to-noise ratio, and lower limit of
      detection compared to TAMRA-cadaverine. Additionally, we successfully used the on
      chip activity assay using the indirect probe to determine TG2 and FXIII
      activities in Hela cell lysates and human plasma samples, respectively. These
      results demonstrate that the reporter tag of the substrate probe is critical for
      protocol execution, sensitivity, and dynamic range of enzyme activity assays.
      Furthermore, this study provides a helpful guide for development of new probes,
      which is necessary for the identification of potential biomarkers and therapeutic
      targets for treating enzyme-related diseases. 

PMID- 24140602
TI  - Shenghua Decoction reduces uterine bleeding and regulates T-cell paradigm in
      human deciduas of RU486 medical abortion.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Excessive uterine bleeding is the most common and
      problematic side effect of RU486 medical abortion. Shenghua Decoction (SHD) is a
      well-known traditional Chinese herbal prescription for reducing uterine bleeding
      induced by RU486 medical abortion. However, its therapeutic mechanism still
      remains unclear. The Th1/Th2/Th17/Treg paradigm plays an important role in
      achieving maternal-fetal immunotolerance and its bias participates in RU486
      induced abortion. Our previous research on mice demonstrated that the uterine
      bleeding volume is negatively related to the proportions of Th1 and Th17 cells
      whereas positively related to the proportions of Th2 and Treg cells.
      Additionally, Th1-type cytokine inducing effect was identified in our previous
      study. Therefore, it was hypothesized that SHD reduced the uterine bleeding in
      RU486 medical abortion by inducing Th1/Th2/Th17/Treg paradigm bias. The purpose
      of this study was to determine the regulatory effect and the mechanism of SHD on
      human decidual Th1/Th2/Th17/Treg paradigm for alleviating uterine bleeding in
      RU486 medical abortion. MATERIALS AND METHODS: 90 women within seven weeks of a
      normal intrauterine pregnancy, who elected for termination of pregnancy, were
      divided into three groups; vacuum aspiration group, RU486 group, and SHD-RU486
      group. Duration of uterine bleeding was recorded and volume of uterine bleeding
      was measured by the method of alkaline hematin photometric. To determine the
      regulatory effect of SHD on Th1/Th2/Th17/Treg paradigm, the proportions of
      Th1/Th2/Th17/Treg cells in the decidua of different groups were analyzed using a
      FACS calibur. Correlation was analyzed in order to demonstrate the relationship
      between the Th1/Th2/Th17/Treg paradigm and the uterine bleeding in RU486 medical
      abortion. Moreover, to elucidate the mechanism underlying the T-cell paradigm
      regulating of SHD, the mRNA and protein expressions of subset-specific
      transcription factors (T-bet, GATA-3, RORgammat, and Foxp3) for the
      differentiation of Th1/Th2/Th17/Treg paradigm in human decidual CD4(+) T cells
      were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay
      and western blot analysis respectively. Moreover, the mRNA expression of the
      characteristic cytokines of Th1/Th2/Th17/Treg paradigm (IFNgamma, IL-4, IL-17A,
      TGF-beta) were analyzed by RT-PCR assay. RESULT: Compared with RU486 group, both
      the uterine bleeding volume and duration reduced significantly in SHD-RU486
      group. Both the duration and the volume of the uterine bleeding demonstrated
      negative correlation with the proportions of Th1 and Th17 cells, whereas showed
      positive correlation with Th2 and Treg cells. SHD increased the proportions of
      Th1 and Th17 cells whereas decreased those of Th2 and Treg cells. Thus, the
      ratios of Th1/Th2 and Th17/Treg cells elevated markedly after SHD treatment. SHD
      promoted the mRNA as well as the protein expressions of subset-specific
      transcription factors for the differentiation of Th1 and Th17 subsets (T-bet and
      RORgammat) while inhibited those of Th2 and Treg cells (GATA-3 and Foxp3).
      Moreover, the mRNA expression of Th1- and Th17- type cytokines (IFNgamma and IL
      17A) was up-regulated while that of Th2-type and Treg-produced cytokines (IL-4
      and TGF-beta) was down-regulated significantly after SHD administration.
      CONCLUSION: Th1/Th2/Th17/Treg paradigm bias was involved in RU486 medical
      abortion. SHD reduced the uterine bleeding efficiently by inducing Th1 and Th17
      skews in the maternal-fetal of RU486 medical abortion patients. The regulatory
      effect of SHD on Th1/Th2/Th17/Treg paradigm in RU486 medical abortion is
      attributed to the modulation of transcription and protein expression of subset
      specific transcription factors for T-cell subsets differentiation and their
      characteristic cytokines.

PMID- 24140603
TI  - A biomimetic extracellular matrix for cartilage tissue engineering centered on
      photocurable gelatin, hyaluronic acid and chondroitin sulfate.
AB  - The development of hydrogels tailored for cartilage tissue engineering has been a
      research and clinical goal for over a decade. Directing cells towards a
      chondrogenic phenotype and promoting new matrix formation are significant
      challenges that must be overcome for the successful application of hydrogels in
      cartilage tissue therapies. Gelatin-methacrylamide (Gel-MA) hydrogels have shown
      promise for the repair of some tissues, but have not been extensively
      investigated for cartilage tissue engineering. We encapsulated human chondrocytes
      in Gel-MA-based hydrogels, and show that with the incorporation of small
      quantities of photocrosslinkable hyaluronic acid methacrylate (HA-MA), and to a
      lesser extent chondroitin sulfate methacrylate (CS-MA), chondrogenesis and
      mechanical properties can be enhanced. The addition of HA-MA to Gel-MA constructs
      resulted in more rounded cell morphologies, enhanced chondrogenesis as assessed
      by gene expression and immunofluorescence, and increased quantity and
      distribution of the newly synthesized extracellular matrix (ECM) throughout the
      construct. Consequently, while the compressive moduli of control Gel-MA
      constructs increased by 26 kPa after 8 weeks culture, constructs with HA-MA and
      CS-MA increased by 114 kPa. The enhanced chondrogenic differentiation,
      distribution of ECM, and improved mechanical properties make these materials
      potential candidates for cartilage tissue engineering applications.

PMID- 24140604
TI  - Late-outgrowth endothelial progenitors from patients with coronary artery
      disease: endothelialization of confluent stromal cell layers.
AB  - Patients with coronary artery disease (CAD) are the primary candidates to receive
      small-diameter tissue-engineered blood vessels (TEBVs). Peripheral blood derived
      endothelial progenitor cells (EPCs) from CAD patients (CAD EPCs) represent a
      minimally invasive source of autologous cells for TEBV endothelialization. We
      have previously shown that human CAD EPCs are highly proliferative and express
      many of the hallmarks of mature and healthy endothelial cells; however, their
      behavior on stromal cells that comprise the media of TEBVs has not yet been
      evaluated. Primary CAD EPCs or control human aortic endothelial cells (HAECs)
      were seeded over confluent, quiescent layers of human smooth muscle cells (SMCs)
      using a direct co-culture model. The percent coverage, adhesion strength,
      alignment under flow and generation of flow-induced nitric oxide of the seeded
      CAD EPCs were compared to that of HAECs. The integrin-binding profile of CAD EPCs
      was also evaluated over a layer of confluent, quiescent SMCs. Direct comparison
      of our CAD EPC results to analogous co-culture studies with cord blood EPCs show
      that both types of blood-derived EPCs are viable options for endothelialization
      of TEBVs. 

PMID- 24140605
TI  - Strain effects in a single ZnO microwire with wavy configurations.
AB  - We investigate strain-induced optical modulation in a ZnO microwire with wavy
      geometries induced by mechanical strains. Curved sections of the wavy ZnO
      microwire show red-/blue-shifts of near-band-edge emission and broadening of full
      width at half maximum in cathodoluminescence spectra along the length of the wavy
      ZnO microwire, compared with straight sections. The observed variations indicate
      that local strains in the wavy ZnO microwire lead to strain-dependent local
      changes of its energy band structure. The local bending curvature calculations
      using a geometric model also provide correlation between the shift of the near
      band-edge emission peaks and the bending strain. 

PMID- 24140606
TI  - Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2,
      hemeoxygenase and carboxylesterase expression in human dental pulp cells.
AB  - The toxic effect of urethane dimethacrylate (UDMA), a major dental resin monomer,
      on human dental pulp is not fully clear. In this study, we investigated the
      influence of UDMA on the cytotoxicity, cell cycle distribution, apoptosis and
      related gene expression of dental pulp cells. The role of reactive oxygen
      species, hemeoxygenase-1 (HO-1) and carboxylesterase (CES) in UDMA cytotoxicity,
      was evaluated. UDMA induced morphological changes of pulp cells and decreased
      cell viability by 29-49% at concentrations of 0.1-0.35 mM. UDMA induced G0/G1,
      G2/M cell cycle arrest and apoptosis. The expression of cdc2, cyclinB1 and cdc25C
      was inhibited by UDMA. Moreover, UDMA stimulated COX-2, HO-1 and CES2 mRNA
      expression of pulp cells. The cytotoxicity of UDMA was attenuated by N-acetyl-l
      cysteine, catalase and esterase, but was enhanced by Zn-protoporphyrin (HO-1
      inhibitor), BNPP (CES inhibitor) and loperamide (CES2 inhibitor). Exposure of
      UDMA may potentially induce the inflammation and toxicity of dental pulp. These
      findings are important for understanding the clinical response of human pulp to
      resin monomers after operative restoration and pulp capping, and also provide
      clues for improvement of dental materials.

PMID- 24140607
TI  - Enhanced antimicrobial properties, cytocompatibility, and corrosion resistance of
      plasma-modified biodegradable magnesium alloys.
AB  - Magnesium alloys are potential biodegradable materials and have received
      increasing attention due to their outstanding biological performance and
      mechanical properties. However, rapid degradation in the physiological
      environment and potential toxicity limit clinical applications. Recently, special
      magnesium-calcium (Mg-Ca) and magnesium-strontium (Mg-Sr) alloys with
      biocompatible chemical compositions have been reported, but the rapid degradation
      still does not meet clinical requirements. In order to improve the corrosion
      resistance, a rough, hydrophobic and ZrO(2)-containing surface film is fabricated
      on Mg-Ca and Mg-Sr alloys by dual zirconium and oxygen ion implantation. Weight
      loss measurements and electrochemical corrosion tests show that the corrosion
      rate of the Mg-Ca and Mg-Sr alloys is reduced appreciably after surface
      treatment. A systematic investigation of the in vitro cellular response and
      antibacterial capability of the modified binary magnesium alloys is performed.
      The amounts of adherent bacteria on the Zr-O-implanted and Zr-implanted samples
      diminish remarkably compared to the unimplanted control. In addition,
      significantly enhanced cell adhesion and proliferation are observed from the Zr-O
      implanted sample. The results suggest that dual zirconium and oxygen ion
      implantation, which effectively enhances the corrosion resistance, in vitro
      biocompatibility and antimicrobial properties of Mg-Ca and Mg-Sr alloys, provides
      a simple and practical means to expedite clinical acceptance of biodegradable
      magnesium alloys.

PMID- 24140608
TI  - Core-shell molecularly imprinted polymer nanoparticles with assistant recognition
      polymer chains for effective recognition and enrichment of natural low-abundance
      protein.
AB  - Core-shell molecular imprinting of nanomaterials overcomes difficulties with
      template transfer and achieves higher binding capacities for macromolecular
      imprinting, which are more important to the imprinting of natural low-abundance
      proteins from cell extracts. In the present study, a novel strategy of preparing
      core-shell nanostructured molecularly imprinted polymers (MIPs) was developed
      that combined the core-shell approach with assistant recognition polymer chains
      (ARPCs). Vinyl-modified silica nanoparticles were used as support and ARPCs were
      used as additional functional monomers. Immunoglobulin heavy chain binding
      protein (BiP) from the endoplasmic reticulum (ER) was chosen as the model
      protein. The cloned template protein BiP was selectively assembled with ARPCs
      from their library, which contained numerous limited-length polymer chains with
      randomly distributed recognition and immobilization sites. The resulting complex
      was copolymerized onto the surface of vinyl-modified silica nanoparticles under
      low concentrations of the monomers. After template removal, core-shell-structured
      nanoparticles with a thin imprinted polymer layer were produced. The particles
      demonstrated considerably high adsorption capacity, fast adsorption kinetics and
      selective binding affinities toward the template BiP. Furthermore, the
      synthesized MIP nanoparticles successfully isolated cloned protein BiP from
      protein mixtures and highly enriched BiP from an ER extract containing thousands
      of kinds of proteins. The enrichment reached 115-fold and the binding capacity
      was 5.4 MUg g(-1), which were higher than those achieved by using traditional MIP
      microspheres. The advantageous properties of MIP nanoparticles hold promise for
      further practical applications in biology, such as protein analysis and
      purification.

PMID- 24140609
TI  - Zinc in calcium phosphate mediates bone induction: in vitro and in vivo model.
AB  - Zinc-containing tricalcium phosphate (Zn-TCP) was synthesized to investigate the
      role of zinc in osteoblastogenesis, osteoclastogenesis and in vivo bone induction
      in an ectopic implantation model. Zinc ions were readily released in the culture
      medium. Zn-TCP with the highest zinc content enhanced the alkaline phosphatase
      activity of human bone marrow stromal cells and tartrate-resistant acid
      phosphatase activity, as well as multinuclear giant cell formation of RAW264.7
      monocyte/macrophages. RAW264.7 cultured with different dosages of zinc
      supplements in medium with or without zinc-free TCP showed that zinc could
      influence both the activity and the formation of multinuclear giant cells. After
      a 12-week implantation in the paraspinal muscle of canines, de novo bone
      formation and bone incidence increased with increasing zinc content in Zn-TCP -
      up to 52% bone in the free space. However, TCP without zinc induced no bone
      formation. Although the observed bone induction cannot be attributed to zinc
      release alone, these results indicate that zinc incorporated in TCP can modulate
      bone metabolism and render TCP osteoinductive, indicating to a novel way to
      enhance the functionality of this synthetic bone graft material. 

PMID- 24140610
TI  - The effects of pulsed electromagnetic field on the functions of osteoblasts on
      implant surfaces with different topographies.
AB  - The use of pulsed electromagnetic fields (PEMFs) is a promising approach to
      promote osteogenesis. However, few studies have reported the effects of this
      technique on the osseointegration of endosseous implants, especially with regard
      to different implant topographies. We focused on how the initial interaction
      between cells and the titanium surface is enhanced by a PEMF and the possible
      regulatory mechanisms in this study. Rat osteoblasts were cultured on three types
      of titanium surfaces (Flat, Micro and Nano) under PEMF stimulation or control
      conditions. Protein adsorption was significantly increased by the PEMF. The
      number of osteoblasts attached to the surfaces in the PEMF group was
      substantially greater than that in the control group after 1.5h incubation. PEMF
      stimulation oriented the osteoblasts perpendicular to the electromagnetic field
      lines and increased the number of microfilaments and pseudopodia formed by the
      osteoblasts. The cell proliferation on the implant surfaces was significantly
      promoted by the PEMF. Significantly increased extracellular matrix mineralization
      nodules were observed under PEMF stimulation. The expression of osteogenesis
      related genes, including BMP-2, OCN, Col-1,ALP, Runx2 and OSX, were up-regulated
      on all the surfaces by PEMF stimulation. Our findings suggest that PEMFs enhance
      the osteoblast compatibility on titanium surfaces but to different extents with
      regard to implant surface topographies. The use of PEMFs might be a potential
      adjuvant treatment for improving the osseointegration process. 

PMID- 24140611
TI  - Decanoic acid-modified glycol chitosan hydrogels containing tightly adsorbed
      palmityl-acylated exendin-4 as a long-acting sustained-release anti-diabetic
      system.
AB  - Decanoic acid-modified glycol chitosan (DA-GC) hydrogels containing tightly
      adsorbed palmitic acid-modified exendin-4 (Ex4-C16) were prepared, and their
      pharmaceutical abilities as a long-acting sustained-release exendin-4 system for
      the treatment of diabetes were evaluated. Glycol chitosan (GC) was conjugated
      with N-hydroxysuccinimide-activated decanoic acid (DA) in anhydrous 0.4%
      dimethylaminopyridine/dimethylsulfoxide at different feed ratios. DA-GC hydrogels
      formed by physical self-assembly during dialysis vs. deionized water, and their
      inner network structures, swelling or gel-forming abilities and release
      properties were examined. The hypoglycemia caused by Ex4-C16-loaded DA-GC
      hydrogels was evaluated by subcutaneous administration in type 2 diabetic db/db
      mice. The results obtained showed that GC prepared at a DA:GC feed ratio of 1:100
      had optimal properties with respect to hydrogel swelling, stiffness and Ex4-C16
      incorporation, whereas DA-GC hydrogels prepared at a feed ratio of greater than
      1:100 formed gels that were too stiff. The in vitro and in vivo release of Ex4
      C16 from DA-GC hydrogels was dramatically delayed compared with native Ex4
      probably due to strong hydrophobic interactions. In particular, Ex4-C16 in DA-GC
      hydrogels was found to be present around the injection site up to 10 days after
      subcutaneous administration, whereas Ex4 in DA-GC hydrogels was cleared from
      injection sites in ~ 2 days in ICR mice. Finally, the hypoglycemia induced by Ex4
      C16 DA-GC hydrogels was maintained for >7 days. Our findings demonstrate that Ex4
      C16 DA-GC hydrogels offer a potential delivery system for the long-term treatment
      of type 2 diabetes.

PMID- 24140613
TI  - Neospora caninum: Activity of cholinesterases during the acute and chronic phases
      of an experimental infection in gerbils.
AB  - Neosporosis is an infectious disease primarily of dogs and cattle which has been
      found in many countries around the world. Neospora caninum causes an important
      immune response (cellular and humoral) in animals that it infects. Since the
      participation of the cholinergic system in the immune response is well
      documented, the aim of this study was to evaluate the relationship between N.
      caninum infection and activities of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) during the acute and chronic phase of infection. For
      that, tachyzoites of N. caninum (Nc-1 strain) were inoculated intraperitoneally
      in gerbils (Meriones unguiculatus), which were separated in two experiments, I
      and II, differing in infective doses of tachyzoites, aiming to reach an acute
      phase as well as chronic phase, respectively. Samples were collected on day 7
      post infection (PI) for Experiment I and on days 15 and 30 PI for Experiment II.
      AChE activity was evaluated on whole blood and brain, while BChE was evaluated in
      plasma. On day 7 a reduction of AChE in total blood and brain was observed, along
      with reduction of BChE in plasma of infected animals when compared with non
      infected. In Experiment II, AChE activity increased in total blood on day 30 PI;
      however, maintaining, during the same period, the AChE activity has a reduced in
      brain tissue. BChE activity was significantly increased on day 30 PI. Based on
      the results obtained, it was possible to observe a response of the cholinergic
      system, providing different grades of AChE and BChE activities, in response to
      the acute and chronic infection of gerbils experimentally infected with N.
      caninum. These results will serve as initial points to further studies of our
      research group about the relationship between the infection/disease and the
      cholinergic system.

PMID- 24140614
TI  - Robot-assisted Heller myotomy for achalasia: technique and results.
AB  - Since its first description in 1991, laparoscopic Heller myotomy has been
      associated with better short-term outcomes and shorter recovery time, compared to
      open operation and it is now generally accepted as the procedure of choice for
      achalasia. Despite the well-known short-term benefits of laparoscopy, esophageal
      perforation still occurs. Robotic technology has recently been introduced into
      laparoscopic clinical practice with the aim of improving surgical performance and
      excellent results have been described with robotically assisted Heller myotomy in
      patients with achalasia. The 3-D visualization, the very steady operative view
      and, above all, the articulated arms of the da Vinci Robotic Surgical System
      allow the surgeon to visualize and divide each individual muscular fiber, easily
      identifying the submucosal plane at the GE junction. However, no high-quality
      studies are available in literature. Moreover, from an economic point of view,
      the use of the robotic technology may increase both the costs and the volume of
      surgeries performed.

PMID- 24140612
TI  - Multifunctional role of osteopontin in directing intrafibrillar mineralization of
      collagen and activation of osteoclasts.
AB  - Mineralized collagen composites are of interest because they have the potential
      to provide a bone-like scaffold that stimulates the natural processes of
      resorption and remodeling. Working towards this goal, our group has previously
      shown that the nanostructure of bone can be reproduced using a polymer-induced
      liquid-precursor (PILP) process, which enables intrafibrillar mineralization of
      collagen with hydroxyapatite to be achieved. This prior work used polyaspartic
      acid (pASP), a simple mimic for acidic non-collagenous proteins, to generate
      nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate
      the interstices of type-I collagen fibrils. In this study we show that
      osteopontin (OPN) can similarly serve as a process-directing agent for the
      intrafibrillar mineralization of collagen, even though OPN is generally
      considered a mineralization inhibitor. We also found that inclusion of OPN in the
      mineralization process promotes the interaction of mouse marrow-derived
      osteoclasts with PILP-remineralized bone that was previously demineralized, as
      measured by actin ring formation. While osteoclast activation occurred when pASP
      was used as the process-directing agent, using OPN resulted in a dramatic effect
      on osteoclast activation, presumably because of the inherent arginine-glycine
      aspartate acid ligands of OPN. By capitalizing on the multifunctionality of OPN,
      these studies may lead the way to producing biomimetic bone substitutes with the
      capability of tailorable bioresorption rates. 

PMID- 24140615
TI  - Humanoid robotics in health care: An exploration of children's and parents'
      emotional reactions.
AB  - A new non-pharmacological method of distraction was tested with 57 children
      during their annual flu vaccination. Given children's growing enthusiasm for
      technological devices, a humanoid robot was programmed to interact with them
      while a nurse administered the vaccination. Children smiled more often with the
      robot, as compared to the control condition, but they did not cry less. Parents
      indicated that their children held stronger memories for the robot than for the
      needle, wanted the robot in the future, and felt empowered to cope. We conclude
      that children and their parents respond positively to a humanoid robot at the
      bedside. 

PMID- 24140616
TI  - Trajectories of illness perceptions in persons with chronic illness: An
      explorative longitudinal study.
AB  - Accurate illness perceptions are essential to the self-management of chronic
      illness. This study explored trajectories of illness perceptions in persons with
      morbid obesity (n = 53) and persons with chronic obstructive pulmonary disease (n
      = 52) following a patient education course. Participants completed the Brief
      Illness Perception Questionnaire five times over a 1-year period. Repeated
      measures analysis of variance was employed. Over time, obese participants
      perceived shorter illness duration, fewer consequences, less emotional stress,
      and more personal control. Chronic obstructive pulmonary disease participants had
      initial increases in personal control and understanding, but these changes were
      not maintained throughout the follow-up period. 

PMID- 24140617
TI  - Relationship between body mass index and women's body image, self-esteem and
      eating behaviours in pregnancy: a cross-cultural study.
AB  - This study examined the relationship between self-esteem, restrained eating, body
      image and body mass index during pregnancy. A total of 110 pregnant Israeli and
      UK women completed the Rosenberg Self-Esteem Questionnaire, the Dutch Eating
      Behaviour Questionnaire, scales to assess body image and demographics. Body mass
      index was calculated from antenatal records. Regression modelling determined the
      relationship between variables, countries and body mass index categories. High
      correlations were found between body image and body mass index with significantly
      higher body dissatisfaction for Israeli women. Self-esteem scores for pregnant
      women were similar to those reported for non-pregnant women. Poorer body image
      and higher prevalence of restrained eating were found in healthy weight Israeli
      women. 

PMID- 24140618
TI  - A simulation of current focusing and steering with penetrating optic nerve
      electrodes.
AB  - OBJECTIVE: Current focusing and steering are both widely used to shape the
      electric field and increase the number of distinct perceptual channels in neural
      stimulation, yet neither technique has been used for an optic nerve (ON)-based
      visual prosthesis. In order to evaluate the effects of current focusing and
      steering in penetrative stimulation, we built an integrated computational model
      to simulate and investigate the influence of stimulating parameters on ON fibre
      recruitment. APPROACH: Finite element models with extremely fine meshes were
      first established to compute the 3D electric potential distribution under
      different stimulating parameters. Then the external electric potential was fed to
      randomized multi-compartment cable models to predict the distribution of fibres
      generating an action potential. Finally a statistical process was conducted to
      quantify the recruitment region. MAIN RESULTS: The simulation results show that a
      two-electrode mode is superior to a three-electrode mode in current steering. The
      three-electrode mode performs poorly in current focusing, albeit the localized
      recruitment from both configurations implies that current focusing might be
      unnecessary in penetrative ON stimulation. SIGNIFICANCE: This study provides
      useful information for the optimized design of penetrating ON electrodes and
      stimulating strategies. The Monte Carlo style computation paradigm is designed to
      simulate neural responses of an ensemble of ON fibres, which can be immediately
      transferred to other similar problems.

PMID- 24140619
TI  - Changes in cardiac innervation during maturation in long-term diabetes.
AB  - Diabetic autonomic neuropathy being a common complication of diabetes mellitus
      (DM) is related to an increased risk of cardiovascular mortality. However,
      mechanisms underlying changes of innervation density in affected hearts remain
      insufficiently understood. Hence, the aim of this study was to describe
      quantitative changes of intra-myocardial nerve terminals in hearts of diabetic
      rats of various ages. Male Sprague-Dawley rats were injected with 55mg/kg
      streptozotocin (STZ) (DM group) or with citrate buffer (control). After 2weeks,
      2months, 6months and 12months, sections of their hearts were analyzed in five
      areas-left ventricle, interventricular septum, right ventricle, anterior and
      posterior wall. Nerve fibers were visualized immunohistochemically, using
      antibody against a general neuronal marker, protein gene product 9.5 (PGP 9.5).
      Significant increase in total nerve fibers from all heart areas was observed
      2weeks and 2months after diabetes induction, followed by a decrease at 6months
      and again increase at 12months was observed in both control and diabetic rats.
      Significant difference between control and diabetic rats was visible after 2weeks
      and 2months, with diabetic rats exhibiting significantly more nerve fibers. There
      were no consistent differences in quantity of nerve fibers in different areas of
      the heart within a particular age-related group of animals. In conclusion,
      cardiac innervation undergoes dynamic changes both in control and in diabetic
      rats, with a time-dependent significant increase in neuronal fiber density in
      diabetic animals. This novel information may contribute to our understanding of
      pathophysiological changes associated with diabetic cardiac neuropathy. 

PMID- 24140620
TI  - Increased Th17 differentiation in aged mice is significantly associated with high
      IL-1beta level and low IL-2 expression.
AB  - OBJECTIVE: Aging has been reported to be associated with changes in immune
      function. Although frequent infection and the development of malignancy suggest
      the decline of immune function with aging, changes toward proinflammatory
      conditions also develop at the same time. Th17 cells are well known CD4(+) T cell
      subpopulation closely linked to chronic inflammation and autoimmunity. In this
      study, changes in the Th17 population were investigated to elucidate a possible
      mechanism for this response with aging. METHODS: Splenocytes were isolated from 2
      month-old (young) and 20-month-old (aged) mice. CD4(+)CD44(+) memory T cells and
      CD4(+)CD62L(+) naive T cells were isolated and sorted using magnetic beads and
      flow cytometry. The frequency of IL-17-producing cells was measured using flow
      cytometry. The expression of IL-17 and Th17-related factors at the mRNA level was
      measured with RT-PCR. IL-17 and Il-1beta expression in spleen tissues was
      additionally assessed using confocal microscopy. RESULTS: The proportion of IL-17
      producing CD4(+) T cells was higher in the splenocytes among the old mice than
      those of the young mice. When splenocytes were cultured in Th17 polarizing
      conditions, the proportion of IL-17 producing CD4(+) T cells was higher in aged
      mice as well. This was consistently observed when naive and memory cells were
      isolated and differentiated into Th17 respectively. In addition, the expression
      of retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat) and
      other Th17-related factors (AhR, CCR6, and CCL20) increased in the splenocytes of
      aged mice compared to the young mice. The expression of IL-1beta, showing to
      promote Th17 differentiation, was higher in the aged mice. Likewise, CD4(+) T
      cell expression of IL-1R was higher in the aged mice, suggesting that the CD4(+)
      T cells of the aged mice are readily prepared to differentiate into Th17 cells in
      response to IL-1beta. Confocal microscopy showed that cells positive for IL-1R or
      IL-1beta were more frequent in the spleens of the aged mice. When an anti-IL-2
      antibody was applied, the proportion of IL-17-producing cells increased more
      prominently in the young mice. We observed that IL-2 production and IL-2R
      expression were reduced in the aged mice, respectively, explaining the blunted
      response to the anti-IL-2 antibody treatment and the consequent minimal change in
      the Th17 population. CONCLUSION: We demonstrated that the proportion of Th17
      cells increased in the aged mice both in naive and memory cell populations.
      Elevation of IL-1R and IL-1beta expression and the reduction in IL-2 and IL-2R
      expression in aged mice seemed to promote Th17 differentiation. Our results
      suggest that enhanced Th17 differentiation in aging may have a pathogenic role in
      the development of Th17-mediated autoimmune diseases.

PMID- 24140621
TI  - Simplified method of clinical phenotyping for older men and women using
      established field-based measures.
AB  - The purpose of this investigation was to determine body composition
      classification using field-based testing measurements in healthy elderly men and
      women. The use of isoperformance curves is presented as a method for this
      determination. Baseline values from 107 healthy Caucasian men and women, over the
      age of 65years old, who participated in a separate longitudinal study, were used
      for this investigation. Field-based measurements of age, height, weight, body
      mass index (BMI), and handgrip strength were recorded on an individual basis.
      Relative skeletal muscle index (RSMI) and body fat percentage (FAT%) were
      determined by dual-energy X-ray absorptiometry (DXA) for each participant.
      Sarcopenia cut-off values for RSMI of 7.26kg.m(-2) for men and 5.45kg.m(-2) for
      women and elderly obesity cut-off values for FAT% of 27% for men and 38% for
      women were used. Individuals above the RSMI cut-off and below the FAT% cut-off
      were classified in the normal phenotype category, while individuals below the
      RSMI cut-off and above the FAT% cut-off were classified in the sarcopenic-obese
      phenotype category. Prediction equations for RSMI and FAT% from sex, BMI, and
      handgrip strength values were developed using multiple regression analysis. The
      prediction equations were validated using double cross-validation. The final
      regression equation developed to predict FAT% from sex, BMI, and handgrip
      strength resulted in a strong relationship (adjusted R(2)=0.741) to DXA values
      with a low standard error of the estimate (SEE=3.994%). The final regression
      equation developed to predict RSMI from the field-based testing measures also
      resulted in a strong relationship (adjusted R(2)=0.841) to DXA values with a low
      standard error of the estimate (SEE=0.544kg.m(-2)). Isoperformance curves were
      developed from the relationship between BMI and handgrip strength for men and
      women with the aforementioned clinical phenotype classification criteria. These
      visual representations were used to aid in the classification and evaluation of
      sarcopenia, obesity, and sarcopenic-obesity in elderly individuals. Future
      research should replicate the current findings with an increased sample size and
      the development of tailored interventions for each body composition category. 

PMID- 24140622
TI  - Sampling scheme and compressed sensing applied to solid-state NMR spectroscopy.
AB  - We describe the incorporation of non-uniform sampling (NUS) compressed sensing
      (CS) into oriented sample (OS) solid-state NMR for stationary aligned samples and
      magic angle spinning (MAS) Solid-state NMR for unoriented 'powder' samples. Both
      simulated and experimental results indicate that 25-33% of a full linearly
      sampled data set is required to reconstruct two- and three-dimensional solid
      state NMR spectra with high fidelity. A modest increase in signal-to-noise ratio
      accompanies the reconstruction. 

PMID- 24140623
TI  - Measuring small compartment dimensions by probing diffusion dynamics via Non
      uniform Oscillating-Gradient Spin-Echo (NOGSE) NMR.
AB  - Noninvasive measurements of microstructure in materials, cells, and in biological
      tissues, constitute a unique capability of gradient-assisted NMR. Diffusion
      diffraction MR approaches pioneered by Callaghan demonstrated this ability;
      Oscillating-Gradient Spin-Echo (OGSE) methodologies tackle the demanding gradient
      amplitudes required for observing diffraction patterns by utilizing constant
      frequency oscillating gradient pairs that probe the diffusion spectrum, D(omega).
      Here we present a new class of diffusion MR experiments, termed Non-uniform
      Oscillating-Gradient Spin-Echo (NOGSE), which dynamically probe multiple
      frequencies of the diffusion spectral density at once, thus affording direct
      microstructural information on the compartment's dimension. The NOGSE methodology
      applies N constant-amplitude gradient oscillations; N-1 of these oscillations are
      spaced by a characteristic time x, followed by a single gradient oscillation
      characterized by a time y, such that the diffusion dynamics is probed while
      keeping (N-1)x+y=TNOGSE constant. These constant-time, fixed-gradient-amplitude,
      multi-frequency attributes render NOGSE particularly useful for probing small
      compartment dimensions with relatively weak gradients - alleviating difficulties
      associated with probing D(omega) frequency-by-frequency or with varying
      relaxation weightings, as in other diffusion-monitoring experiments. Analytical
      descriptions of the NOGSE signal are given, and the sequence's ability to extract
      small compartment sizes with a sensitivity towards length to the sixth power, is
      demonstrated using a microstructural phantom. Excellent agreement between theory
      and experiments was evidenced even upon applying weak gradient amplitudes. An MR
      imaging version of NOGSE was also implemented in ex vivo pig spinal cords and
      mouse brains, affording maps based on compartment sizes. The effects of size
      distributions on NOGSE are also briefly analyzed. 

PMID- 24140624
TI  - SENSASS NMR: New NMR techniques for enhancing the sensitivity and the spectral
      resolution of polymer supported chemicals.
AB  - The use of polyethylene glycols (PEGs) as organic polymer soluble supports for
      synthesis has been receiving growing interest. The main advantages of using PEGs
      as support are related to their non-toxicity, their commercial availability and
      their solubility properties allowing easy recovery and analysis of compounds
      linked to the polymer. The NMR characterization of PEG-branched products could
      however be difficult due to the presence of huge signals of the polymeric
      support. In order to overcome this problem, we developed new NMR experiments
      named SENSitivity increAsed and resolution enhanced by Signal Suppression or
      SENSASS NMR. These experiments implement either semi-selective pulses or Water
      Gate sequences for reducing signals of the polymer as well as fast pulsing
      techniques optimizing the recycling delay for enhancing the sensitivity of
      signals. They have been successfully implemented in classical NMR
      characterization experiments namely, COSY, HSQC and HMBC experiments. 

PMID- 24140625
TI  - Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and
      isoniazid.
AB  - Hyperpolarization produces nuclear spin polarization that is several orders of
      magnitude larger than that achieved at thermal equilibrium thus providing
      extraordinary contrast and sensitivity. As a parahydrogen induced polarization
      (PHIP) technique that does not require chemical modification of the substrate to
      polarize, Signal Amplification by Reversible Exchange (SABRE) has attracted a lot
      of attention. Using a prototype parahydrogen polarizer, we polarize two drugs
      used in the treatment of tuberculosis, namely pyrazinamide and isoniazid. We
      examine this approach in four solvents, methanol-d4, methanol, ethanol and DMSO
      and optimize the polarization transfer magnetic field strength, the temperature
      as well as intensity and duration of hydrogen bubbling to achieve the best
      overall signal enhancement and hence hyperpolarization level. 

PMID- 24140627
TI  - Cotton leaf curl Gezira alphasatellite associated with tomato leaf curl Sudan
      virus approaches the expected upper size limit in the evolution of
      alphasatellites.
AB  - Begomoviruses (family Geminiviridae) cause severe damage to tomato crops
      worldwide. Among them, tomato leaf curl disease (ToLCD)-associated begomoviruses
      are a major concern for tomato production in Sudan. Here, we report the detection
      of unexpectedly large cotton leaf curl Gezira alphasatellite molecules (up to
      1467 nt) associated with an isolate of a novel strain of tomato leaf curl Sudan
      virus (ToLCSDV) in tomato plants affected by ToLCD. A recombinant nature is
      suggested for this ToLCSDV isolate. 

PMID- 24140626
TI  - Examining sources of variation in HPG axis function among individuals and
      populations of the dark-eyed junco.
AB  - Gonadal steroids are important mediators of traits relevant to fitness, and thus
      may be targets of selection. However, more knowledge is needed about sources of
      variation along the endocrine axes that may contribute to functional variation in
      steroid levels. In a controlled captive environment, we studied males of two
      closely related subspecies of the dark-eyed junco (Junco hyemalis) that differ in
      testosterone-related phenotype, asking whether they also differ in testosterone
      (T), and assessing the contribution of the sequential links of the hypothalamic
      pituitary-gonadal axis. When males of both subspecies were challenged with
      gonadotropin-releasing hormone (GnRH), they were similar in circulating
      luteinizing hormone (LH) and T responses. When challenged with exogenous LH, they
      again produced levels of T similar to one another, and to the levels produced in
      response to GnRH. However, the smaller, less ornamented, and less aggressive
      subspecies had greater abundance of mRNA for LH receptor in the testes and for
      androgen receptor in the rostral hypothalamus, suggesting potential differences
      in regulatory feedback. We suggest that circulating hormone levels may be less
      prone to evolutionary change than the responsiveness of individual hormone
      targets. Among individuals, T titers were highly repeatable whether males were
      challenged with GnRH or with LH, but LH produced in response to GnRH did not
      covary with T produced in response to LH. Testis mass, but not LH receptor
      transcript abundance, predicted individual variation in T responses. These data
      implicate the gonad, but not the pituitary, as an important source of individual
      variation in T production. 

PMID- 24140628
TI  - IRF3 helps control acute TMEV infection through IL-6 expression but contributes
      to acute hippocampus damage following TMEV infection.
AB  - IRF3 is an innate anti-viral factor whose role in limiting Theiler's murine
      encephalomyelitis virus (TMEV) infection and preventing TMEV-induced disease is
      unclear. Acute disease and innate immune responses of macrophages were examined
      in IRF3 knockout mice compared with C57Bl/6 mice following in vitro or
      intracranial infection with either TMEV GDVII or DA. IRF3 deficiency augmented
      viral infection, as well as morbidity and mortality following intracranial
      infection with neurovirulent TMEV GDVII. In contrast, IRF3 deficiency prevented
      hippocampal injury following intracranial infection with persistent TMEV DA. The
      extent of TMEV infection in macrophages from C57Bl/6 mice was significantly less
      than that in IRF3 deficient macrophages, which was associated with poor IFN-beta
      and IL-6 expression in response to TMEV. Reestablishing IRF3 expression in IRF3
      deficient macrophages increased control of TMEV replication and increased
      expression of IFN-beta and IL-6. In addition, IRF3 deficient macrophages failed
      to exhibit IL-6 antiviral effects, which was associated with inability to sustain
      IL-6-induced STAT1 activation compared with C57BL/6 macrophages. Altogether, IRF3
      contributes to early control of TMEV replication through induction of IL-6 and
      IFN-beta and support of IL-6 antiviral effects, but contributes to TMEV-induced
      hippocampal injury. 

PMID- 24140629
TI  - Efficacy of recombinant chimeric lectins, consisting of mannose binding lectin
      and L-ficolin, against influenza A viral infection in mouse model study.
AB  - Influenza A virus infection could result in fatal complications. Although
      immunization is the most effective prevention it is not effective to pandemic
      infection and is less effective or not approved for certain age groups. Some
      influenza virus strains have developed resistance to antiviral agents. Thus, new
      therapeutic agents are urgently needed. We focused on innate immune molecules,
      including mannose-binding lectin (MBL). In order to optimize its antiviral
      activities, we have previously generated three recombinant chimeric lectins
      (RCL), by introducing portions of L-ficolin, another innate immune lectin. Our in
      vitro characterizations previously selected RCL2 and RCL3 for further
      investigations against viruses, including influenza viruses. Here, we examined
      efficacy of these lectins against infection with PR8 (H1N1) influenza A virus
      using mouse model studies and a human tracheal epithelial cell system. Our
      results provide in vivo evidence that RCL3 is effective agent against influenza
      virus infection. The therapeutic mechanisms are in part by providing host
      protective responses mediated by cytokines. We conclude that RCL3 is a potential
      new innate immune anti-influenza virus therapeutic agent. 

PMID- 24140630
TI  - Association of contemporary sensitive troponin I levels at baseline and change at
      1 year with long-term coronary events following myocardial infarction or unstable
      angina: results from the LIPID Study (Long-Term Intervention With Pravastatin in
      Ischaemic Disease).
AB  - OBJECTIVES: This study sought to assess whether baseline and change in
      contemporary sensitive troponin I (TnI) levels predicts coronary heart disease
      (CHD) death and myocardial infarction (MI), and to determine the effects of
      pravastatin on TnI levels. BACKGROUND: The role of troponins in predicting long
      term outcomes in patients with stable CHD is not clearly defined. METHODS: The
      LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) study
      randomized patients with cholesterol levels of 155 to 271 mg/dl 3 to 36 months
      after MI or unstable angina to placebo or pravastatin 40 mg per day. TnI levels
      were measured at baseline and after 1 year in 7,863 patients. Median follow-up
      was 6 years. Change in TnI was defined as moving up or down 1 tertile or >=50%
      change. RESULTS: Baseline TnI tertiles were <0.006 ng/ml, 0.006 to <0.018 ng/ml,
      and >=0.018 ng/ml. TnI levels were related to CHD death and MI after adjustment
      for 23 risk factors and treatment (>=0.018 ng/ml vs. <0.006 ng/ml hazard ratio
      [HR]: 1.64; 95% CI: 1.41 to 1.90; p < 0.001). TnI levels increased in 23.0%, were
      unchanged in 51.3%, and decreased in 25.7% of patients. Pravastatin decreased TnI
      levels by 0.003 ng/ml versus placebo (p = 0.002). In landmark analyses, increases
      in TnI levels were associated with increased numbers of CHD death and MI (HR:
      1.31; 95% CI: 1.06 to 1.62) and decreases with decreased risk (HR: 0.90; 95% CI:
      0.74 to 1.09; overall p = 0.01). Data were similar with 50% change criteria. Net
      reclassification improvement by adding TnI to the baseline model for CHD death
      and MI was 4.8% (p = 0.01). CONCLUSIONS: Baseline TnI levels and change at 1 year
      are independent predictors of CHD death and MI. TnI levels are strong predictors
      of risk, and change modifies risk.

PMID- 24140631
TI  - Optimization of upcyte(r) human hepatocytes for the in vitro micronucleus assay.
AB  - "Upcyte((r)) human hepatocytes" have the unique property of combining
      proliferation with the expression of drug metabolising activities. In our current
      study, we evaluated whether these cells would be suitable for early in vitro
      micronucleus (MN) tests. A treatment period of 96 h without a recovery period was
      most reliable for detecting MN formation in upcyte((r)) hepatocytes from Donor
      740. The basal MN rate in upcyte((r)) hepatocytes varied considerably between
      donors (7-28%); therefore, modifications to the assay medium were tested to
      determine whether they could decrease inherent MN formation. Optimal medium
      supplements were 10 ng/ml oncostatin M for the pre-culture and recovery periods
      and 25 ng/ml epidermal growth factor and 10 ng/ml oncostatin M for the treatment
      period. Using the optimised conditions and outcome criteria, the upcyte((r))
      hepatocyte MN assay could correctly identify directly acting (e.g. mitomycin C,
      etoposide) and metabolically activated genotoxins (e.g. benzo[a]pyrene,
      cyclophosphamide). "True negative" and "false positive" compounds were also
      correctly identified as negative. The basal %MN in upcyte((r)) hepatocytes from
      Donor 740 treated with DMSO, cyclophosphamide or MMC, was essentially unaffected
      by the growth stage ranging from population doublings of 14-61, suggesting that
      billions of cells could be produced from a single donor for standardised drug
      toxicity testing. In conclusion, we have established and optimised an in vitro MN
      test by using upcyte((r)) hepatocytes to correctly identify known direct and
      metabolically activated genotoxicants as well as "false positives" and true
      negative compounds. The almost unlimited supply of cells from a single donor and
      optimised test conditions increase reproducibility in early and more predictive
      in vitro MN tests.

PMID- 24140632
TI  - A four-day oral treatment regimen for simultaneous micronucleus analyses in the
      glandular stomach, colon, and bone marrow of rats.
AB  - Our aim was to develop a multi-tissue micronucleus (MN) test method for the
      simultaneous analysis of rat glandular stomach, colon, and bone marrow. We have
      evaluated the multi-tissue MN test method with a regimen in which rats were
      administered chemicals orally once per day for four days and the cells of each
      tissue were collected 24 h after the final dose. The following compounds were
      studied: N-nitroso-N-methylurea (MNU), 4-nitroquinoline-1-oxide (4NQO), N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N-nitrosourethane (NMUT), 1,2
      dimethylhydrazine 2HCl (DMH), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine HCl
      (PhIP), KBrO(3), amaranth (AM), and quercetin (QN). The gastrointestinal tract
      carcinogens increased the frequencies of micronucleated (MNed) cells in target
      tissue in a dose-dependent manner: MNU in gastric- and colonic-cells; 4NQO, MNNG,
      and NMUT in gastric cells; DMH and PhIP in colonic cells. In immature
      erythrocytes, MNU, 4NQO, DMH, and PhIP increased the frequency of MNed cells but
      MNNG and NMUT did not. The food additive KBrO(3), which is known to be a renal
      carcinogen, increased the frequencies of MNed cells in the glandular stomach and
      bone marrow. The food additive AM and the plant flavonoid QN, which are non
      carcinogenic in most studies, did not cause increased MNed cells in any of the
      three tissues. Our results indicate that this multi-tissue MN test method is
      useful for the comprehensive evaluation of the genotoxicity of orally
      administered compounds.

PMID- 24140633
TI  - Cholinesterases and neurotoxicity as highly sensitive biomarkers for an
      organophosphate insecticide in a freshwater gastropod (Chilina gibbosa) with low
      sensitivity carboxylesterases.
AB  - In the Upper Valley of Rio Negro and Rio Neuquen in Argentina, agriculture
      represents the second most important economic activity. Azinphos-methyl has been
      found in water from this region throughout the year at a maximum concentration of
      22.48 MUg L(-1) during the application period. Toxicological studies on local non
      target species have been performed mostly on vertebrates, while mollusks, which
      could be more sensitive, have not been studied so far. This work aims to
      characterize cholinesterase (ChE) and carboxilesterase (CE) activities of Chilina
      gibbosa, a freshwater gastropod native to southern Argentina and Chile. These
      enzymes, together with neurotoxicity signals, are evaluated herein after as
      sensitive biomarkers of exposure to azinphos-methyl at environmentally relevant
      concentrations. Effects of azinphos-methyl on antioxidant defenses: glutathione
      (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase
      (GST) are also studied in order to complete a set of biomarkers with different
      sensitivity and specificity, to propose C. gibbosa as a sentinel species. The
      highest specific activity was obtained with acetylthiocholine as substrate,
      followed by propionylthiocholine (83% in comparison to acetylthiocholine) and
      butyrylthiocholine (19%).The lowest Km and the highest efficiency for ChE were
      obtained with acetylthiocholine. Regarding CEs activities, a higher efficiency
      was obtained with p-nitrophenyl butyrate than with p-nitrophenyl acetate. Eserine
      produced significant inhibition of ChE activity (81% with 0.001 mM and 98% with
      1mM) while iso-OMPA did not produce any significant effect on ChE. Our results
      show that C. gibbosa ChE is very sensitive to azinphos-methyl (CI50 0.02 MUg L(
      1)) while CEs are inhibited at higher concentrations (CI50 1,000 MUg L(-1)). CEs
      have been reported to be more sensitive to OPs than ChEs in most of the aquatic
      invertebrates protecting the organisms from neurotoxic effects. In contrast, C.
      gibbosa, has ChE which are much more sensitive to azinphos-methyl than CEs and
      shows marked signs of neurotoxicity. Regarding antioxidant defenses, GSH levels
      were significantly increased by 0.02 and 20 MUg L(-1) azinphos-methyl (80 and
      103%, respectively), CAT activity was increased 85% only at 0.02 MUg L(-1) and
      SOD and GST did not show any significant response. Since ChE activity,
      neurotoxicity signs, GSH and CAT are sensitive biomarkers of acute exposure to
      azinphos-methyl at environmental concentrations C. gibbosa could be included as
      sentinel species in monitoring programs of pesticide hazard in regions of
      Argentina and Chile.

PMID- 24140634
TI  - A rapid screening test for endocrine disrupting chemicals using primary cell
      culture of the marine medaka.
AB  - While endocrine disrupting chemicals (EDCs) pose a significant threat to wildlife
      worldwide, their diverse chemical structures present a major challenge to their
      detection, particularly since they are present at very low concentrations in the
      environment. We here report the development of an in vitro system for rapid
      screening of EDCs, using primary cell cultures (pituitary, ovarian follicular and
      testicular cells) of the marine medaka (Oryzias melastigma). Pituitary, testis
      and ovary cell cultures were developed and challenged by environmentally relevant
      concentrations of three well known EDCs (viz. estradiol, 2,2',4,4'
      tetrabromodiphenyl ether, and 4-n-nonylphenol) as well as hypoxia (which has been
      shown to be a potent endocrine disruptor). In general, the mRNA expression levels
      of gonadotropins, their receptors and steroidogenic enzymes exhibited dose
      response relationships to the four endocrine disruptors in different tissues. The
      sensitivity and responses were also comparable to in vivo responses of whole fish
      and in vitro responses of the H295R human adrenocortical cell line. Our results
      suggest that the use of marine medaka primary cultured cells can serve as a cost
      effective tool for rapid screening of EDCs in the marine environment, and at the
      same time, sheds light on the underlying mechanisms of EDCs by deciphering their
      specific target sites along the hypothalamus-pituitary-gonad axis of vertebrates.

PMID- 24140635
TI  - Dynamic expression of miR-126* and its effects on proliferation and contraction
      of hepatic stellate cells.
AB  - In our previous study, miR-126 was identified as one of the leading miRNAs that
      is downregulated during activation of hepatic stellate cells (HSCs). However, the
      roles and related mechanisms of miR-126 in HSCs are not understood. In this
      study, we compared expression of miR-126 during HSC activation both in vitro and
      in vivo. We also applied RNA interference to analyze the role and mechanism of
      miR-126(*) in the activation of HSCs. Restoring HSCs with Lv-miR-126(*) resulted
      in decreased proliferation, accumulation of extracellular matrix components, and
      cell contraction, while also negatively regulating the vascular endothelial
      growth factor (VEGF) signal transduction pathways by partially targeted VEGF-A.
      Thus, we postulate that miR-126 may be a biological marker for the activation of
      HSCs, and useful for reducing intrahepatic vascular resistance and improving the
      sinusoidal microcirculation in chronic liver diseases.

PMID- 24140636
TI  - Determination of HSV-1 UL5 and UL29 gene copy numbers in an HSV complementing
      Vero cell line.
AB  - The genetic stability of transgenes is a critical characteristic used to assess
      constructed cell lines used for vaccine production. The evaluation of gene copy
      numbers by a qPCR method, is one of the most common approaches used to assess the
      consistency of transgenes in a constructed cell line. The cell line AV529-19 is a
      Vero-based cell line specifically engineered to express the HSV-1 UL5 and UL29
      open reading frames. AV529-19 is used to support the replication of a defective
      HSV-2 viral candidate vaccine called HSV529. To assess the genetic stability of
      the UL5 and UL29 transgenes in AV529-19 cells, a digital PCR-based approach was
      developed. During characterization of the test method, the specificity, accuracy,
      and intermediate precision of the assay was investigated based on regulatory
      guidelines. The developed assay was used to monitor the stability of the
      transgenes in the manufactured AV529-19 cell lines by comparison of transgene
      copy numbers in the master cell bank (MCB) with their copy numbers in the
      extended cell bank (ECB). Results showed that the UL29 and UL5 transgenes are
      stable in that there are one and three copies of the UL29 and UL5 genes,
      respectively, per cell in both the AV529-19 MCB and ECB.

PMID- 24140637
TI  - Fluorescein-labeled "arch-like" DNA probes for electrochemical detection of DNA
      on gold nanoparticle-modified gold electrodes.
AB  - In the present study, a gold nanoparticle-modified gold electrode (nanogold
      electrode) was used to develop a novel fluorescein electrochemical DNA biosensor
      based on a target-induced conformational change. The nanogold electrode was
      obtained by electrodepositing gold nanoparticles onto a bare gold electrode. This
      modification not only immobilized probe oligonucleotides, but also adsorbed
      fluorescein onto the surface of the gold nanoparticles to form an "arch-like"
      structure. This article compares the electrochemical signal changes caused by the
      hybridization of "arch-like" DNA on nanogold electrode and linear DNA on bare
      gold electrode. The results showed that the adsorption effect of nanogold can
      enhance the sensitivity of the sensor. The linear range of target ssDNA is from
      2.0 * 10(-9)M to 2.0 * 10(-8)M with a correlation coefficient of 0.9956 and
      detection limit (3sigma) of 7.10 * 10(-10)M. Additionally, the specificity and
      hybridization response of this simple sensor were investigated.

PMID- 24140638
TI  - Distinct roles of carbohydrate esterase family CE16 acetyl esterases and polymer
      acting acetyl xylan esterases in xylan deacetylation.
AB  - Mass spectrometric analysis was used to compare the roles of two acetyl esterases
      (AE, carbohydrate esterase family CE16) and three acetyl xylan esterases (AXE,
      families CE1 and CE5) in deacetylation of natural substrates, neutral (linear)
      and 4-O-methyl glucuronic acid (MeGlcA) substituted xylooligosaccharides (XOS).
      AEs were similarly restricted in their action and apparently removed in most
      cases only one acetyl group from the non-reducing end of XOS, acting as exo
      deacetylases. In contrast, AXEs completely deacetylated longer neutral XOS but
      had difficulties with the shorter ones. Complete deacetylation of neutral XOS was
      obtained after the combined action of AEs and AXEs. MeGlcA substituents partially
      restricted the action of both types of esterases and the remaining acidic XOS
      were mainly substituted with one MeGlcA and one acetyl group, supposedly on the
      same xylopyranosyl residue. These resisting structures were degraded to great
      extent only after inclusion of alpha-glucuronidase, which acted with the
      esterases in a synergistic manner. When used together with xylan backbone
      degrading endoxylanase and beta-xylosidase, both AE and AXE enhanced the
      hydrolysis of complex XOS equally. 

PMID- 24140639
TI  - Comparison of the atomic level structure of the plastic crystalline and liquid
      phases of CBr2Cl2: neutron diffraction and reverse Monte Carlo modelling.
AB  - Neutron diffraction results obtained for plastic crystalline
      dichlorodibromomethane (CBr2Cl2) have been modelled by means of the reverse Monte
      Carlo method. Comparison with its liquid phase is provided at several levels of
      the atomic structure (total scattering structure factors, partial radial
      distribution functions, orientational and dipole-dipole correlations). The
      results reveal that the relative orientation of neighbouring molecules largely
      depends on the steric effect. The small dipole moment does not have as strong an
      influence as the steric effect on the short-range order. Our observations fit
      well with earlier findings presented for the series CBr(n)Cl(4-n) (n = 0, 1, 2,
      4).

PMID- 24140640
TI  - Two novel distinct COL1A2 mutations highlight the complexity of genotype
      phenotype correlations in osteogenesis imperfecta and related connective tissue
      disorders.
AB  - Osteogenesis imperfecta is a heritable connective tissue disorder characterized
      by variable symptoms including predisposition to fractures. Despite the
      identification of numerous mutations, a reliable genotype-phenotype correlation
      has remained notoriously difficult. We now describe two patients with
      osteogenesis imperfecta and novel, so far undescribed mutations in the COL1A2
      gene, further highlighting this complexity. A 3-year-old patient presented with
      features reminiscent of a connective tissue disorder, with joint hypermobility,
      Wormian bones, streaky lucencies in the long bones and relative macrocephaly. The
      patient carried a heterozygous c.1316G > A (p.Gly439Asp) mutation in the COL1A2
      gene located in a triple-helix region, in which glycine substitutions have been
      assumed to cause perinatal lethal OI (Sillence type II). A second family with
      type I osteogenesis imperfecta carried a heterozygous nonsense mutation c.4060C >
      T (p.Gln1354X) within the last exon of COL1A2. Whereas other heterozygous
      nonsense mutations in COL1A2 do not lead to a phenotype, in this case the mRNA is
      presumed to escape nonsense-mediated decay. Therefore the predicted COL1A2
      propeptide lacks the last 13 C-terminal amino acids, suggesting that the OI
      phenotype results from decelerated assembly and overmodification of the collagen
      triple helix. The presented COL1A2 mutations exemplify the complexity of COL1A2
      genotype-phenotype correlation in genetic counselling in OI.

PMID- 24140641
TI  - A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a
      region upstream of SOX9.
AB  - The 46, XX male disorder of sex development (DSD) is a rare genetic condition.
      Here, we report the case of a 46, XX SRY-negative male with complete
      masculinization. The coding region and exon/intron boundaries of the DAX1, SOX9
      and RSPO1 genes were sequenced, and no mutations were detected. Using whole
      genome array analysis and real-time PCR, we identified a approximately 74-kb
      duplication in a region approximately 510-584 kb upstream of SOX9
      (chr17:69,533,305-69,606,825, hg19). Combined with the results of previous
      studies, the minimum critical region associated with gonadal development is a 67
      kb region located 584-517 kb upstream of SOX9. The amplification of this region
      might lead to SOX9 overexpression, causing female-to-male sex reversal. Gonadal
      specific enhancers in the region upstream of SOX9 may activate the SOX9
      expression through long-range regulation, thus triggering testicular
      differentiation.

PMID- 24140642
TI  - TNF-like ligand 1A (TL1A) gene knockout leads to ameliorated collagen-induced
      arthritis in mice: implication of TL1A in humoral immune responses.
AB  - TNF-like ligand 1A (TL1A), also known as TNFSF15, is a member of the TNF
      superfamily. Its known receptor is death receptor 3 (DR3). In humans, TL1A also
      binds to a secreted TNF family member called decoy receptor 3, which interferes
      with the interaction between TL1A and DR3. TL1A/DR3 signal has been implicated in
      several autoimmune diseases in animal models as well as in clinical conditions.
      We generated TL1A gene knockout (KO) mice to assess its role in collagen-induced
      arthritis (CIA), a mouse model of human rheumatoid arthritis. The KO mice were
      fertile and had no visible anomalies. Their lymphoid organ size and cellularity,
      T and B cell subpopulations, Th cell and regulatory T cell development in vivo
      and in vitro, and antiviral immune responses were comparable to those of wild
      type mice. However, the KO mice presented ameliorated CIA in terms of clinical
      scores, disease incidence, and pathological scores. The KO mice had reduced
      titers of pathogenic anti-collagen Abs in the sera. No apparent defect was found
      in the function of follicular Th cells. We revealed that plasma cells but not B
      cells expressed high levels of DR3 and were direct targets of TL1A. In the
      presence of TL1A, they survived better and produced more pathogenic Ab. This
      study presented novel knowledge about the role of TL1A in humoral immune
      responses and its mechanism of action in CIA pathogenesis. 

PMID- 24140643
TI  - Adrenergic regulation of IgE involves modulation of CD23 and ADAM10 expression on
      exosomes.
AB  - Soluble CD23 plays a role in the positive regulation of an IgE response.
      Engagement of the beta2 adrenergic receptor (beta2AR) on a B cell is known to
      enhance the level of both soluble CD23 and IgE, although the mechanism by which
      this occurs is not completely understood. In this study, we report that, in
      comparison with a CD40 ligand/IL-4-primed murine B cell alone, beta2AR engagement
      on a primed B cell increased gene expression of a disintegrin and
      metalloproteinase (ADAM)10, which is the primary sheddase of CD23, as well as
      protein expression of both CD23 and ADAM10, in a protein kinase A- and p38 MAPK
      dependent manner, and promoted the localization of these proteins to exosomes as
      early as 2 d after priming, as determined by both Western blot and flow cytometry
      and confirmed by electron microscopy. In comparison with isolated exosomes
      released from primed B cells alone, the transfer of exosomes released from
      beta2AR agonist-exposed primed B cells to cultures of recipient primed B cells
      resulted in an increase in the level of IgE produced per cell, without affecting
      the number of cells producing IgE, as determined by ELISPOT. These effects still
      occurred when a beta2AR antagonist was added along with the transfer to block
      residual agonist, and they failed to occur when exosomes were isolated from
      beta2AR-deficient B cells. These findings suggest that the mechanism responsible
      for mediating the beta2AR-induced increase in IgE involves a shuttling of the
      beta2AR-induced increase in CD23 and ADAM10 proteins to exosomes that
      subsequently mediate an increase in IgE. 

PMID- 24140644
TI  - Hepatocytes contribute to immune regulation in the liver by activation of the
      Notch signaling pathway in T cells.
AB  - The "liver tolerance effect" has been attributed to a unique potential of liver
      resident nonprofessional APCs including hepatocytes (HCs) to suppress T cell
      responses. The exact molecular mechanism of T cell suppression by liver APCs is
      still largely unknown. In mice, IL-10-dependent T cell suppression is observed
      after Th1-mediated hepatitis induced by Con A. In this study, we show that HCs,
      particularly those from regenerating livers of Con A-pretreated mice, induced a
      regulatory phenotype in naive CD4(+) T cells in vitro. Using reporter mice, we
      observed that these T regulatory cells released substantial amounts of IL-10,
      produced IFN-gamma, failed to express Foxp3, but suppressed proliferation of
      responder T cells upon restimulation with anti-CD3 mAb. Hence, these regulatory
      cells feature a similar phenotype as the recently described IL-10-producing Th1
      cells, which are generated upon activation of Notch signaling. Indeed, inhibition
      of gamma-secretase and a disintegrin and metalloproteinase 17 but not a
      disintegrin and metalloproteinase 10, respectively, which blocked Notch
      activation, prevented IL-10 secretion. HCs from Con A-pretreated mice showed
      enhanced expression of the Notch ligand Jagged1 and significantly increased
      receptor density of Notch1 on CD4(+) T cells. However, HCs from Con A-pretreated
      IFN regulatory factor 1(-/-) mice, which cannot respond to IFN-gamma, as well as
      those from IFN-gamma(-/-) mice failed to augment IL-10 production by CD4(+) T
      cells. In conclusion, it seems that HCs fine-tune liver inflammation by
      upregulation of Jagged1 and activation of Notch signaling in Th1 cells. This
      mechanism might be of particular importance in the regenerating liver subsequent
      to Th1-mediated hepatitis. 

PMID- 24140645
TI  - Cytomegalovirus-seropositive children show inhibition of in vitro EBV infection
      that is associated with CD8+CD57+ T cell enrichment and IFN-gamma.
AB  - EBV, a human herpesvirus, is commonly acquired during childhood and persists
      latently in B cells. EBV seropositivity has been connected to immunomodulatory
      effects such as altered T and NK cell functional responses as well as protection
      against early IgE sensitization; however, owing to the asymptomatic presentation
      during childhood little is known regarding the infection process in children of
      different ages. In this study, we used mononuclear cells from cord blood and from
      2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the
      degree of EBV-induced B cell activation and expansion differs between age groups
      and in particular in relationship to IFN-gamma production capacity. EBV infection
      induced redistribution between B cell subsets with enrichment of IgD(+)CD27(+)
      cells (commonly referred to as non-switched memory) in infected cord blood cell
      cultures, and of IgD(-)CD27(+) cells (switched memory) in cell cultures from
      older children. We also related results to serostatus to CMV, a persistent
      herpesvirus that can affect differentiation status of T and NK cells. As compared
      with CMV(-) children, the EBV-induced enrichment of IgD(-)CD27(+) B cells was
      significantly reduced in infected cell cultures from CMV(+) children. This effect
      was associated with high levels of IFN-gamma and frequencies of highly mature
      CD8(+)CD57(+) T cells in CMV(+) children. Our results demonstrate that both a
      child's age and serostatus to CMV will have an impact on EBV-induced B cell
      activation and expansion, and they point to the ability of viruses with
      immunomodulatory functions, such as CMV, to affect immune responses within the
      host system. 

PMID- 24140647
TI  - Functional analysis of SleC from Clostridium difficile: an essential lytic
      transglycosylase involved in spore germination.
AB  - Clostridium difficile is the most common cause of enteric disease and presents a
      major burden on healthcare systems globally due in part to the observed rapid
      rise in antibiotic resistance. The ability of C. difficile to form endospores is
      a key feature in the organism's pathogenesis and transmission, and contributes
      greatly to its resilient nature. Endospores are highly resistant to disinfection,
      allowing them to persist on hospital surfaces. In order for the organism to cause
      disease, the spores must germinate and revert to a vegetative form. While spore
      germination in Bacillus spp. is well understood, very little is known about this
      process in Clostridia. Here we report the characterization of SleC (CD0551) from
      C. difficile 630. Bioinformatic analysis of SleC indicated a multi-domained
      protein possessing a peptidoglycan-binding (PGB) domain, a SpoIID/LytB domain and
      an undefined N-terminal region. We have confirmed that SleC is an exo-acting
      lytic transglycosylase with the catalytic activity localized to the N-terminal
      region. Additionally, we have shown that both the N-terminal catalytic domain and
      the C-terminal PGB domain require muramyl-delta-lactam for substrate binding. As
      with carbohydrate-binding modules from cellulases and xylanases, the PGB domain
      may be responsible for increasing the processivity of SleC by concentrating the
      enzyme at the surface of the substrate. 

PMID- 24140646
TI  - TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis.
AB  - Chronic debilitating pruritus is a cardinal feature of atopic dermatitis (AD).
      Little is known about the underlying mechanisms. Antihistamines lack efficacy in
      treating itch in AD, suggesting the existence of histamine-independent itch
      pathways in AD. Transient receptor potential ankyrin 1 (TRPA1) is essential in
      the signaling pathways that promote histamine-independent itch. In this study, we
      tested the hypothesis that TRPA1-dependent neural pathways play a key role in
      chronic itch in AD using an IL-13-transgenic mouse model of AD. In these mice, IL
      13 causes chronic AD characterized by intensive chronic itch associated with
      markedly enhanced growth of dermal neuropeptide-secreting afferent nerve fibers
      and enhanced expression of TRPA1 in dermal sensory nerve fibers, their dorsal
      root ganglia, and mast cells. Inhibition of TRPA1 with a specific antagonist in
      these mice selectively attenuated itch-evoked scratching. Genetic deletion of
      mast cells in these mice led to significantly diminished itch-scratching
      behaviors and reduced TRPA1 expression in dermal neuropeptide containing
      afferents in the AD skin. Interestingly, IL-13 strongly stimulates TRPA1
      expression, which is functional in calcium mobilization in mast cells. In
      accordance with these observations in the AD mice, TRPA1 expression was highly
      enhanced in the dermal afferent nerves, mast cells, and the epidermis in the
      lesional skin biopsies from patients with AD, but not in the skin from healthy
      subjects. These studies demonstrate a novel neural mechanism underlying chronic
      itch in AD and highlight the complex interactions among TRPA1(+) dermal afferent
      nerves and TRPA1(+) mast cells in a Th2-dominated inflammatory environment. 

PMID- 24140648
TI  - A non-catalytic histidine residue influences the function of the metalloprotease
      of Listeria monocytogenes.
AB  - Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are
      synthesized as proenzymes by the intracellular bacterial pathogen Listeria
      monocytogenes. During intracellular growth, L. monocytogenes is temporarily
      confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis
      and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation
      also leads to the secretion of both Mpl and PC-PLC across the bacterial cell
      wall. Previously, we identified negatively charged and uncharged amino acid
      residues within the N terminus of the PC-PLC propeptide that influence the
      ability of Mpl to mediate the maturation of PC-PLC, suggesting that these
      residues promote the interaction of the PC-PLC propeptide with Mpl. In the
      present study, we identified a non-catalytic histidine residue (H226) that
      influences Mpl secretion across the cell wall and its ability to process PC-PLC.
      Our results suggest that a positive charge at position 226 is required for Mpl
      functions other than autolysis. Based on the charge requirement at this position,
      we hypothesize that this residue contributes to the interaction of Mpl with the
      PC-PLC propeptide. 

PMID- 24140649
TI  - Non-invasive metabolomic profiling of day 3 embryo culture media using near
      infrared spectroscopy to assess the development potential of embryos.

PMID- 24140650
TI  - New microbiota found in sputum from patients with community-acquired pneumonia.
AB  - Community-acquired pneumonia (CAP) is a major concern in hospitals and the
      bacterial community of which has not been systemically discussed yet. Sputum from
      patients in the acute stages is a kind of accessible sample reflecting its
      features. In our study, we analyzed 45 sputum samples from 45 patients with CAP.
      Eighteen sputum samples from healthy people were chosen as the controls.
      Pyrosequencing of the 16s rDNA V3 hypervariable regions of all the bacteria
      contained in the sputum was used as a culture-independent method to disclose the
      community constitution. Also, our published data for hospital-acquired pneumonia
      (HAP) in sputum was used for comparison. By pyrosequencing, >90,000 DNA reads
      were detected. After being analyzed by tools in the Ribosomal Database Project,
      the reads were classified into five main phyla and >100 genera. At the phyla
      level, the reads' distribution of CAP is similar to that of healthy people and at
      genera level, the occurrence of each genus possesses their feature in three
      categories. Genera such as Streptococcus and Neisseria showed stability in their
      percentages, indicating that such genera are rarely affected by exogenous
      bacteria or antibiotics. The role of other genera such as Moraxella and Rothia in
      CAP should be emphasized. According to our analysis, the bacterial communities of
      CAP are with slight change when compared with those of healthy people, but have a
      large gap between HAP. Meanwhile, Rothia might be an important endogenous
      pneumonia-causing factor. 

PMID- 24140651
TI  - Collective behaviors of mammalian cells on amine-coated silicon nanowires.
AB  - Intensive studies with vertical nanowire (NW) arrays have illustrated broad
      implications for manipulating mammalian cells in vitro, but how cellular
      responses are influenced by the presence of NWs has not been thoroughly
      investigated. Here, we address collective cellular behaviors, including surface
      area of cells, membrane trafficking, focal adhesion distribution and dynamics,
      and cytoskeletal protein distribution on amine-coated silicon (Si) NWs with
      different physical properties. The degree of HeLa cell spreading was inversely
      proportional to the surface area occupied by the NWs, which was not affected by
      manipulation of membrane trafficking dynamics. In the presence of a diffusive
      focal complex around the NWs, strong, well organized focal adhesion was hardly
      visible on the NWs, implying that the cells were interacting weakly with the NW
      embedded surface. Furthermore, we found that actin filament formation of the
      cells on long NWs was not favorable, and this could explain our observation of
      reduced cell spreading, as well as the decreased number of focal adhesion
      complexes. Taken together, our results suggest that cells can survive on silicon
      NWs by adjusting their morphology and adhesion behavior through actively
      organizing these molecules. 

PMID- 24140652
TI  - ATF3 expression is induced by low glucose in pancreatic alpha and beta cells and
      regulates glucagon but not insulin gene transcription.
AB  - The pancreas is critical for maintaining glucose homeostasis. Activating
      transcription factor 3 (ATF3) is an adaptive response transcription factor. There
      are major discrepancies in previous reports on pancreatic ATF3; therefore, its
      role in the pancreas is unclear. To better elucidate the role of ATF3 in the
      pancreas, we conducted in vitro studies using pancreatic alpha and beta cell
      lines, and also evaluated the use of ATF3 antibodies for immunohistochemistry. We
      determined ATF3 expression was increased by low glucose and decreased by high
      glucose in both alphaTC-1.6 and betaTC3 cells. We also showed that adenovirus
      mediated ATF3 overexpression increased glucagon promoter activity and glucagon
      mRNA levels in alphaTC-1.6 cells; whereas, it had no effect on insulin promoter
      activity and insulin mRNA levels in betaTC3 cells. Although immunostaining with
      the C-19 ATF3 antibody demonstrated predominant expression in alpha cells rather
      than beta cells, ATF3 staining was still detected in ATF3 knockout mice as
      clearly as in control mice. On the other hand, another ATF3 antibody (H-90)
      detected ATF3 in both alpha cells and beta cells, and was clearly diminished in
      ATF3 knockout mice. These results indicate that previous discrepancies in ATF3
      expression patterns in the pancreas were caused by the varying specificities of
      the ATF3 antibodies used, and that ATF3 is actually expressed in both alpha cells
      and beta cells. 

PMID- 24140653
TI  - Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry:
      could it raise new perspectives in the diagnostic field of hormone-dependent
      malignancies?
AB  - Breast and prostate constitute organs of intense steroidogenic activity. Clinical
      and epidemiologic data provide strong evidence on the influence of androgens and
      estrogens on the risk of typical hormone-dependent malignancies, like breast and
      prostate cancer. Recent studies have focused on the role of androgen metabolites
      in regulating androgen concentrations in hormone-sensitive tissues. Steroid
      glucuronidation has been suggested to have a prominent role in controlling the
      levels and the biological activity of unconjugated androgens. It is well
      established that serum levels of androgen glucuronides reflect androgen
      metabolism in androgen-sensitive tissues. Quantitative analysis of androgen
      metabolites in blood specimens is the only minimally invasive approach permitting
      an accurate estimate of the total pool of androgens. During the past years,
      androgen glucuronides analysis most often involved radioimmunoassays (RIA) or
      direct immunoassays, both methods bearing serious limitations. However, recent
      impressive technical advances in mass spectrometry, and particularly in high
      performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have
      overcome these drawbacks enabling the simultaneous, quantitative analysis of
      multiple steroids even at low concentrations. Blood androgen profiling by LC
      MS/MS, a robust and reliable technique of high selectivity, sensitivity,
      specificity, precision and accuracy emerges as a promising new approach in the
      study of human pathology. The present review offers a contemporary insight in
      androgen glucuronides profiling through the application of LC-MS/MS, highlighting
      new perspectives in the study of steroids and their implication in hormone
      dependent malignancies. 

PMID- 24140654
TI  - Development of a high performance liquid chromatography method for quantification
      of isomers beta-caryophyllene and alpha-humulene in copaiba oleoresin using the
      Box-Behnken design.
AB  - The sesquiterpene isomers, beta-Cariofileno (CAR) and alpha-Humuleno (HUM) are
      the primary constituents of the copaiba oleoresin species. These natural products
      are primarily used by the Amazonian population and marketed as phytotherapies and
      cosmetics. The aim of this study was to develop and validate a method that
      simultaneously assays the isomers present in copaiba oleoresins by high
      performance liquid chromatography using the Box-Behnken design. After preliminary
      studies, the reverse phase chromatographic system was selected using a cyano
      column and a mobile phase consisting of acetonitrile and phosphate buffer. The
      Box-Behnken design was applied at three levels and with four independent
      variables: flow rate (X1), gradient slope time (X2), proportion of organic
      compounds at the end of the gradient (X3) and at the beginning of the gradient
      (X4). Also, the responses of the dependent variables: CAR retention time (Y1) and
      the resolution between the CAR and HUM peaks (Y2) was assessed. The mathematical
      model obtained from the regression results was satisfactory (R(2)>0.98, n=27) and
      showed a quadratic relationship where the effects of interactions between the
      variables, was observed by response surface graphs. The simultaneous optimization
      method was used to establish the best compromise of the resolution between the
      CAR and HUM isomers while adjusting the retention time of CAR. This method was
      successfully optimized by BBD obtaining chromatographic peaks with good symmetry,
      resolution and separation efficiency. The validation of the developed method
      confirmed its specificity, precision, accuracy and linearity in the range of 5.0
      11.0 and 0.4-1.0MUg/mL for CAR and HUM, respectively, and is considered suitable
      for routine applications which assure quality control. 

PMID- 24140655
TI  - Liquid chromatography-mass spectrometric determination of rufinamide in low
      volume plasma samples.
AB  - Quantification of rufinamide in plasma was achieved using a selective and
      sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)
      method. The chromatographic separation was achieved on a reversed phase column
      (Zorbax SB-C18 100mm*3mm, 3.5MUm) under isocratic conditions. The mobile phase
      consisted of a mixture of water containing 0.1% formic acid and methanol (50:50,
      v/v). The mass spectrometric detection of the analyte was in multiple reaction
      monitoring mode (MRM) using an electrospray positive ionization (ESI positive).
      The monitored ions were 127m/z derived from 239m/z rufinamide and 108m/z derived
      from 251m/z the internal standard (lacosamide). Protein precipitation with
      methanol was applied for sample preparation using only 50MUl aliquots. The
      concentration range was 40-2000ng/ml for rufinamide in plasma. The limit of
      detection was 1.25ng/ml and the lower limit of quantification was established at
      5ng/ml rufinamide concentration. Selectivity and matrix effect was verified using
      individual human, rat and rabbit plasma samples. Short-term, post-preparative and
      freeze-thaw stability was also investigated. The proposed method provides
      accuracy, precision and high-throughput (short runtime 4.5min) for quantitative
      determination of rufinamide in plasma. This is the first reported liquid
      chromatography-tandem mass spectrometric (LC-MS/MS) method for analysis of
      rufinamide from low volume plasma samples. The LC-MS/MS method was validated
      according to the current official guidelines and can be applied to accurately
      measure rufinamide level of large number of plasma samples from clinical studies
      or therapeutic drug monitoring. 

PMID- 24140656
TI  - MCM-41 solid phase membrane tip extraction combined with liquid chromatography
      for the determination of non-steroidal anti-inflammatory drugs in human urine.
AB  - Mesoporous silica material, MCM-41, was utilized for the first time as an
      adsorbent in solid phase membrane tip extraction (SPMTE) of non-steroidal anti
      inflammatory drugs (NSAIDs) in urine prior to high performance liquid
      chromatography-ultraviolet (HPLC-UV) analysis. The prepared MCM-41 material was
      enclosed in a polypropylene membrane tip and used as an adsorbent in SPMTE. Four
      NSAIDs namely ketoprofen, diclofenac, mefenamic acid and naproxen were selected
      as model analytes. Several important parameters, such as conditioning solvent,
      sample pH, salting-out effect, sample volume, extraction time, desorption solvent
      and desorption time were optimized. Under the optimum extraction conditions, the
      MCM-41-SPMTE method showed good linearity in the range of 0.01-10MUg/mL with
      excellent correlation coefficients (r=0.9977-0.9995), acceptable RSDs (0.4-9.4%,
      n=3), good limits of detection (5.7-10.6MUg/L) and relative recoveries (81.4
      108.1%). The developed method showed a good tolerance to biological sample
      matrices. 

PMID- 24140657
TI  - Long-term prognostic impact of dobutamine stress echocardiography in patients
      with Kawasaki disease and coronary artery lesions: a 15-year follow-up study.
AB  - OBJECTIVES: This study sought to determine the prognostic value of dobutamine
      stress echocardiography (DSE) over a 15-year follow-up for predicting cardiac
      events in adolescent Kawasaki disease (KD) patients with coronary artery lesions
      (CALs). BACKGROUND: Although DSE is an established technique for the detection of
      coronary artery disease, its prognostic value to predict cardiac events in
      adolescent KD patients with CALs is unknown. METHODS: Fifty-eight adolescent KD
      patients, including 36 patients with CALs documented by coronary angiography, and
      22 patients with normal coronary arteries documented by echocardiography who
      underwent DSE were reviewed at initial testing (mean age: 13.6 years) and at 15
      years' follow-up. Follow-up events were tabulated as major adverse cardiac events
      (MACEs) that included cardiac death, nonfatal myocardial infarction, and
      revascularization. RESULTS: During a mean follow-up of 14.7 years, there were 16
      patients with MACEs (acute myocardial infarction: n = 1; old myocardial
      infarction: n = 7; coronary artery bypass grafting: n = 4; percutaneous coronary
      intervention: n = 4). Significant coronary artery disease (CAD) (>70% coronary
      stenosis) was detected in 31.0% of patients at initial testing and 42.1% at
      follow-up. However, there were no significant differences in wall motion score
      indices (WMSI) at peak DSE between initial testing and follow-up (p = 0.762).
      Five of 6 patients (85%) with false-positive DSE results (WMSI: >=1.25) at
      initial testing, who had giant aneurysms without CAD, developed CAD with MACEs
      during follow-up. Cumulative event-free survival rate to 15 years was 25.0% in
      patients with WMSI >=1.25 and 91.7% in patients with WMSI <1.25. Cox regression
      analysis showed the grade of peak WMSI at initial testing to be the only
      independent predictor of MACEs (relative risk: 3.28; 95% confidence interval:
      1.73 to 6.20). CONCLUSIONS: DSE provided independent prognostic information up to
      15 years in adolescent KD survivors.

PMID- 24140658
TI  - Proenkephalin and prognosis after acute myocardial infarction.
AB  - OBJECTIVES: The goal of this research was to assess the prognostic value of
      proenkephalin (PENK) levels in acute myocardial infarction (AMI) by using N
      terminal pro-B-type natriuretic peptide and Global Registry of Acute Coronary
      Events (GRACE) scores as comparators and to identify levels that might be
      valuable in clinical decision making. BACKGROUND: PENK is a stable analyte of
      labile enkephalins. Few biomarkers predict recurrent AMI. METHODS: We measured
      PENK in 1,141 patients (820 male subjects; mean age 66.2 +/- 12.8 years) with
      AMI. Endpoints were major adverse events (composite of death, myocardial
      infarction [MI], and heart failure [HF] hospitalization) and recurrent MI at 2
      years. GRACE scoring was used for comparisons with PENK for the death and/or MI
      endpoint at 6 months. RESULTS: During follow-up, 139 patients died, and there
      were 112 HF hospitalizations and 149 recurrent AMIs. PENK levels were highest on
      admission and were related to estimated glomerular filtration rate, left
      ventricular wall motion index, sex, blood pressure, and age. Multivariable Cox
      regression models found that the PENK level was a predictor of major adverse
      events (hazard ratio [HR]: 1.52 [95% confidence interval (CI): 1.19 to 1.94]),
      death and/or AMI (HR: 1.76 [95% CI: 1.34 to 2.30]), and death and/or HF (HR: 1.67
      [95% CI: 1.24 to 2.25]) (all comparisons p < 0.001), as well as recurrent AMI
      (HR: 1.43 [95% CI: 1.07 to 1.91]; p < 0.01). PENK levels were independent
      predictors of 6-month death and/or MI compared with GRACE scores. PENK-adjusted
      GRACE scores reclassified patients significantly (overall category-free net
      reclassification improvement [>0] of 21.9 [95% CI: 4.5 to 39.4]; p < 0.014). PENK
      levels <48.3 pmol/l and >91 pmol/l detected low- and high-risk patients,
      respectively. CONCLUSIONS: PENK levels reflect cardiorenal status post-AMI and
      are prognostic for death, recurrent AMI, or HF. Cutoff values define low- and
      high-risk groups and improve risk prediction of GRACE scores.

PMID- 24140659
TI  - Outcomes of patients with chronic lung disease and severe aortic stenosis treated
      with transcatheter versus surgical aortic valve replacement or standard therapy:
      insights from the PARTNER trial (placement of AoRTic TraNscathetER Valve).
AB  - OBJECTIVES: The study aimed to evaluate the impact of chronic lung disease (CLD)
      on outcomes of severe aortic stenosis patients across all treatment modalities.
      BACKGROUND: Outcomes of patients with CLD undergoing transcatheter aortic valve
      replacement (TAVR) have not been systematically examined. METHODS: All patients
      who underwent TAVR in the PARTNER (Placement of AoRTic TraNscathetER Valve)
      trial, including the continued access registry (n = 2,553; 1,108 with CLD), were
      evaluated according to CLD clinical severity. Additionally, outcomes of CLD
      patients included in the randomization arms of the PARTNER trial were compared:
      Cohort A patients (high-risk operable) treated by either TAVR (n = 149) or
      surgical aortic valve replacement (SAVR); (n = 138); and Cohort B patients
      (inoperable) treated by either TAVR (n = 72) or standard therapy only (n = 95).
      RESULTS: Among all TAVR-treated patients, at 1-year follow-up, patients with CLD
      had higher mortality than those without it (23.4% vs. 19.6%, p = 0.02). Baseline
      characteristics of CLD patients who underwent TAVR were similar to respective
      controls. In Cohort A, 2-year all-cause death rates were similar (TAVR 35.2% and
      SAVR 33.6%, p = 0.92), whereas in Cohort B, the death rate was lower after TAVR
      (52.0% vs. 69.6% after standard therapy only, p = 0.04). Independent predictors
      for mortality in CLD patients undergoing TAVR included poor mobility (6-min walk
      test <50 m; hazard ratio: 1.67, p = 0.0009) and oxygen-dependency (hazard ratio:
      1.44, p = 0.02). Although CLD patients undergoing TAVR have worse outcomes than
      patients without CLD, TAVR is better in these patients than standard therapy and
      is similar to SAVR. CONCLUSIONS: Although patients with CLD undergoing TAVR had
      worse outcomes than patients without CLD, TAVR performed better in these patients
      than standard therapy and was similar to SAVR. However, CLD patients who were
      either poorly mobile or oxygen-dependent had poor outcomes. (THE PARTNER TRIAL:
      Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

PMID- 24140660
TI  - Human heart rate: heritability of resting and stress values in twin pairs, and
      influence of genetic variation in the adrenergic pathway at a microribonucleic
      acid (microrna) motif in the 3'-UTR of cytochrome b561 [corrected].
AB  - OBJECTIVES: The goal of this study was to understand the role of genetic
      variation in the catecholamine biosynthetic pathway for control of human heart
      rate (HR). BACKGROUND: Human HR is an integrated cardiovascular trait predictive
      of morbidity and survival. Because the autonomic pathway exerts rapid control
      over the heart, we probed the role of heredity in the control of HR, focusing on
      a component of the autonomic sympathetic pathway already predictive of outflow
      responses: cytochrome b561 (CYB561), the electron shuttle in catecholamine
      vesicle membranes for transmitter biosynthesis. METHODS: We studied hereditary
      control of HR with the twin pair design, at rest and during environmental (cold)
      stress. Single nucleotide polymorphism disruption of a microribonucleic acid
      (microRNA) recognition motif in the human CYB561 3'-UTR was identified
      computationally, and its differential effect on gene expression was demonstrated
      in a transfected luciferase reporter/3'-UTR variant. We exposed stem cell-derived
      human embryoid bodies to the microRNA mimic or antagomir oligonucleotides, and we
      observed the effects on contraction rate in proto-hearts. RESULTS: Substantial
      heritability (h(2)) was demonstrated by using twin pair variance components for
      both basal/resting HR (h(2) 50.9 +/- 6.4% of trait variation, p = 2.47 * 10(-10))
      and stress-augmented HR (h(2) 55.1 +/- 5.9%, p = 8.79 * 10(-13)), and the 2 HR
      traits shared genetic determination (genetic covariance rhoG 0.747 +/- 0.058, p =
      2.85 * 10(-9)). CYB561 displayed 1 common genetic variant in the transcript
      region: A+1485G (rs3087776), in the 3'-UTR, 1485 bp downstream of the termination
      codon, in a conserved region, with the A-allele ancestral in primates. In a
      twin/sibling sample (n = 576), A+1485G influenced HR, both at rest (p = 0.010)
      and after environmental stress (p = 0.002), with the minor (A) allele displaying
      a recessive effect with lower HR. The effect of A+1485G on HR was extended by
      meta-analysis into 2 additional population samples (total n = 2,579), and the
      influence remained directionally consistent and significant (p = 0.007). A+1485G
      disrupted a microRNA (human microribonucleic acid-1294 [hsa-miR-1294])
      recognition motif in the 3'-UTR, as demonstrated by a transfected luciferase
      reporter/human 3'-UTR variant system in 2 different neuronal/neuroendocrine cell
      types. The microRNA effect was further documented by cotransfection of an hsa-miR
      1294 mimic, yielding an exaggerated decline in expression of the A-allele (better
      match) reporter (p = 4.3 * 10(-5)). Similar findings of differential 3'-UTR
      allelic susceptibility to hsa-miR-1294 were noted during expression of the full
      length human CYB561 messenger ribonucleic acid with its cognate 3'-UTR. Finally,
      exposure of stem cell-derived human embryoid bodies to hsa-miR-1294 mimic or
      antagomir oligonucleotides yielded directionally opposite effects on contraction
      rate in proto-hearts. CONCLUSIONS: HR is a substantially heritable trait, with
      genetic influence by variation in the adrenergic pathway, here shown for
      messenger ribonucleic acid translational control at the CYB561 step of
      transmitter formation. The results have implications for potentially modifiable
      autonomic pathways that influence this risk trait in the population.

PMID- 24140661
TI  - Cardiac positron emission tomography enhances prognostic assessments of patients
      with suspected cardiac sarcoidosis.
AB  - OBJECTIVES: This study sought to relate imaging findings on positron emission
      tomography (PET) to adverse cardiac events in patients referred for evaluation of
      known or suspected cardiac sarcoidosis. BACKGROUND: Although cardiac PET is
      commonly used to evaluate patients with suspected cardiac sarcoidosis, the
      relationship between PET findings and clinical outcomes has not been reported.
      METHODS: We studied 118 consecutive patients with no history of coronary artery
      disease, who were referred for PET, using [(18)F]fluorodeoxyglucose (FDG) to
      assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD),
      following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose
      uptake. Blind readings of PET data categorized cardiac findings as normal,
      positive PD or FDG, positive PD and FDG. Images were also used to identify
      whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)
      death or sustained ventricular tachycardia (VT)-were ascertained by electronic
      medical records, defibrillator interrogation, patient questionnaires, and
      telephone interviews. RESULTS: Among the 118 patients (age 52 +/- 11 years; 57%
      males; mean ejection fraction: 47 +/- 16%), 47 (40%) had normal and 71 (60%) had
      abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were
      31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were
      predictive of AE, and the presence of both a PD and abnormal FDG (29% of
      patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained
      significant after adjusting for left ventricular ejection fraction (LVEF) and
      clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated
      with AE. CONCLUSIONS: The presence of focal PD and FDG uptake on cardiac PET
      identifies patients at higher risk of death or VT. These findings offer
      prognostic value beyond Japanese Ministry of Health and Welfare clinical
      criteria, the presence of extra-cardiac sarcoidosis and LVEF.

PMID- 24140662
TI  - The role of monocytes in angiogenesis and atherosclerosis.
AB  - New vessel formation inside the arterial wall and atherosclerotic plaques plays a
      critical role in pathogenesis of heart attacks and strokes. The 2 known
      mechanisms resulting in the formation of new vessels within the plaque are local
      ischemia and inflammation. Blood monocytes play an important role in both
      processes. First, they express receptors for vascular endothelial growth factor
      and some of them may serve as circulating ancestors of endothelial cells. Second,
      monocytes are associated with inflammation by synthesis of inflammatory molecules
      following their activation (e.g., after stimulation of Toll-like receptors).
      Neovascularization is a reparative response to ischemia, and includes 3
      processes: angiogenesis, arteriogenesis, and vasculogenesis. Angiogenesis, the
      formation of new capillary vessels is known to occur in response to a hypoxic
      environment. The interaction between leukocytes and vascular wall via
      overexpression of various molecules facilitates the migration of inflammatory
      cells into the plaque microenvironment. Monocytes are intimately involved in
      tissue damage and repair and an imbalance of these processes may have detrimental
      consequences for plaque development and stability. Importantly, monocytes are
      comprised of distinct subsets with different cell surface markers and functional
      characteristics and this heterogeneity may be relevant to angiogenic processes in
      atherosclerosis. The aim of this review article is to present an overview of the
      available evidence supporting a role for monocytes in angiogenesis and
      atherosclerosis.

PMID- 24140663
TI  - Atrial autonomic innervation: a target for interventional antiarrhythmic therapy?
AB  - Atrial fibrillation is the most common arrhythmia and is associated with
      significant morbidity and mortality. The autonomic nervous system contributes to
      the creation of atrial fibrillation substrates. Atrial electrophysiology is
      influenced differently by sympathetic and parasympathetic activation. Several
      strategies are available to modulate the complex interaction between the
      autonomic nervous system and the heart. However, different approaches target the
      problem differently making the prediction of arrhythmogenic and/or antiarrhythmic
      effects difficult. We discuss the role of the autonomic nervous system on the
      development of a substrate for atrial fibrillation and explore the potential
      antiarrhythmic and/or arrhythmogenic effect of modulation of the autonomic
      nervous system by renal sympathetic denervation, ganglionated plexi ablation,
      ganglion stellatum ablation, high thoracic epidural anesthesia, low-level vagal
      nerve stimulation, and baroreflex stimulation. 

PMID- 24140664
TI  - Reduction in cardiac mortality with bivalirudin in patients with and without
      major bleeding: The HORIZONS-AMI trial (Harmonizing Outcomes with
      Revascularization and Stents in Acute Myocardial Infarction).
AB  - OBJECTIVES: The purpose of this study was to determine whether, in patients with
      ST-segment elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (PCI), the reduction in cardiac mortality in
      those taking bivalirudin compared with unfractionated heparin plus a glycoprotein
      IIb/IIIa inhibitor (UFH+GPI) can be fully attributed to reduced bleeding.
      BACKGROUND: The association between hemorrhagic complications and mortality may
      explain the survival benefit with bivalirudin. METHODS: A total of 3,602 STEMI
      patients undergoing primary PCI were randomized to bivalirudin versus UFH+GPI.
      Three-year cardiac mortality was analyzed in patients with and without major
      bleeding. RESULTS: When compared with UFH+GPI, bivalirudin resulted in lower 3
      year rates of major bleeding (6.9% vs. 10.5%, hazard ratio [HR]: 0.64 [95%
      confidence interval (CI): 0.51 to 0.80], p < 0.0001) and cardiac mortality (2.9%
      vs. 5.1%, HR: 0.56 [95% CI: 0.40 to 0.80], p = 0.001). Three-year cardiac
      mortality was reduced in bivalirudin-treated patients with major bleeding (20
      fewer deaths with bivalirudin; 5.8% vs. 14.6%, p = 0.025) and without major
      bleeding (18 fewer deaths with bivalirudin; 2.6% vs. 3.8%, p = 0.048). In a fully
      adjusted multivariable model accounting for major bleeding and other adverse
      events, bivalirudin was still associated with a 43% reduction in 3-year cardiac
      mortality (adjusted HR: 0.57 [95% CI: 0.39 to 0.83], p = 0.003). CONCLUSIONS:
      Bivalirudin reduces cardiac mortality in patients with STEMI undergoing primary
      PCI, an effect that can only partly be attributed to prevention of bleeding.
      Further studies are required to identify the nonhematologic benefits of
      bivalirudin. (Harmonizing Outcomes With Revascularization and Stents in Acute
      Myocardial Infarction; NCT00433966).

PMID- 24140665
TI  - Is therapeutic hypothermia a risk factor for stent thrombosis?

PMID- 24140666
TI  - Highly sensitive noninvasive cardiac transplant rejection monitoring using
      targeted quantification of donor-specific cell-free deoxyribonucleic acid.

PMID- 24140667
TI  - Avoiding unnecessary aggressive ICD programming after MADIT-RIT and ADVANCE III
      trials.

PMID- 24140668
TI  - Positron emission tomography/computed tomography for diagnosis of prosthetic
      valve endocarditis: increased valvular 18F-fluorodeoxyglucose uptake as a novel
      major criterion.

PMID- 24140669
TI  - Reply: positron emission tomography/computed tomography for diagnosis of
      prosthetic valve endocarditis.

PMID- 24140670
TI  - Reply: Avoiding unnecessary aggressive ICD programming after MADIT-RIT and
      ADVANCE III trials.

PMID- 24140671
TI  - Implantable cardioverter-defibrillator lead failure in children and young adults:
      a matter of lead diameter or lead design?
AB  - OBJECTIVES: This study aimed to investigate the impact of lead diameter and
      design on implantable cardioverter-defibrillator (ICD) lead survival in children
      and young adults. BACKGROUND: Recent reports have called attention to high rates
      of lead failure in adults with small-diameter ICD leads, but data in the
      pediatric population is limited. METHODS: We reviewed lead performance in
      consecutive subjects <=30 years with transvenous right ventricular ICD leads
      implanted at our center between January 1995 and October 2011. Lead failure was
      defined as fracture, perforation, or sensing failure necessitating revision.
      RESULTS: A total of 120 ICD leads were implanted in 101 patients at a mean age of
      15.5 +/- 4.9 years. There were 47 small-diameter (<=8-F) and 73 standard-diameter
      (>8-F) leads. During a median follow-up of 28.7 months (interquartile range: 14.4
      to 59.2 months), there were 25 lead failures (21% prevalence), with an incidence
      of 5.6%/year (95% confidence interval: 3.4 to 7.8). Sprint Fidelis (SF)
      (Medtronic, Inc., Minneapolis, Minnesota) leads had lower 3-year (69% vs. 92%, p
      < 0.01) and 5-year (44% vs. 86%, p < 0.01) survival probabilities than standard
      diameter leads. In multivariate Cox regression, SF design conferred the greatest
      hazard ratio for lead failure (hazard ratio: 4.42, 95% confidence interval: 1.73
      to 11.29, p < 0.01). Age and linear growth were not significantly associated with
      lead failure. CONCLUSIONS: In this single-center pediatric study that evaluated
      lead diameter, lead design, and patient factors, the SF design conferred the
      highest risk of lead failure, suggesting that design rather than diameter is the
      critical issue in ICD lead performance.

PMID- 24140672
TI  - Anomalous cord from the raphe of a congenitally bicuspid aortic valve to the
      aortic wall producing either acute or chronic aortic regurgitation.
AB  - OBJECTIVES: This report calls attention to an unappreciated cause of both acute
      and chronic aortic regurgitation (AR). BACKGROUND: Although stenosis develops in
      most patients with a congenitally bicuspid aortic valve (BAV), in others with
      this anomaly, pure AR (no element of stenosis) develops, some in the absence of
      infection or other clear etiology. METHODS: We describe 5 men who underwent
      aortic valve replacement for pure AR associated with a BAV containing an
      anomalous cord attaching the raphe of the conjoined cusp near its free margin to
      the wall of the ascending aorta cephalad to the sinotubular junction. RESULTS:
      Three of these 5 patients had a history of progressive dyspnea, and the anomalous
      cord, which was intact at operation, appeared to cause chronic AR by preventing
      proper coaptation of the 2 aortic valve cusps. The other 2 patients heard a "pop"
      during physical exertion and immediately became dyspneic, and at operation, the
      anomalous cord was found to have ruptured. Prolapse of the conjoined aortic valve
      cusp toward the left ventricular cavity resulted in severe acute AR. CONCLUSIONS:
      This variant of the purely regurgitant BAV may cause either chronic AR (when the
      anomalous cord does not rupture) or acute severe AR (when the cord ruptures).

PMID- 24140673
TI  - Andreas Vesalius' Tabulae anatomicae sex (1538) and the seal of the American
      College of Cardiology.

PMID- 24140674
TI  - Increased vasopressin 1A receptor expression in failing human hearts.

PMID- 24140675
TI  - Ventricular tachycardia associated with a giant right atrial diverticulum.

PMID- 24140676
TI  - Myocardial infiltration by oxalate: a rare case of cardiomyopathy by accumulation
      of oxalate in a 53-year-old woman.

PMID- 24140677
TI  - Short-term and long-term clinical impact of stent thrombosis and graft occlusion
      in the SYNTAX trial at 5 years: Synergy Between Percutaneous Coronary
      Intervention with Taxus and Cardiac Surgery trial.
AB  - OBJECTIVES: The aim of this study was to report the short-term and long-term
      clinical impact of stent thrombosis (ST) and graft occlusion (GO) in the final 5
      year outcomes of the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery)
      trial. BACKGROUND: The clinical effect of newer-generation drug-eluting stents
      and operative factors in complex coronary artery disease is uncertain. METHODS:
      The incidence of 5-year ST and GO, and their association with clinical outcomes,
      were analyzed in the randomized percutaneous coronary intervention and coronary
      artery bypass graft cohorts. ST and GO were defined by the SYNTAX protocol
      definitions (clinical presentation with acute coronary syndrome and
      angiographic/pathological evidence), the Academic Research Consortium (ARC)
      definition for ST, and the newly devised "ARC-like" definition of GO (i.e.,
      definite, probable, or possible GO). RESULTS: At 5 years, 871 of 903 patients
      (96.5%) in the percutaneous coronary intervention cohort and 805 of 897 patients
      (89.7%) in the coronary artery bypass graft cohort completed follow-up. As
      compared with other vessel locations, protocol ST (72 lesions) occurred more
      frequently in the left main (14 of 72; 19%) and proximal coronary vasculature (37
      of 72; 51%) and protocol GO (41 lesions) with grafts anastomosed to the distal
      right coronary artery (17 of 41; 42%). The incidence of 5-year ARC definite ST
      and ARC-like definite GO did not significantly differ (7% [n = 48] vs. 6% [n =
      32], log rank p = 0.34); landmark analyses indicated significantly increased ARC
      definite ST within 30 days (3% [n = 19] vs. 1% [n = 6], log rank p = 0.033) but
      not >30 days to 5 years (4.2% [n = 29] vs. 4.5% [n = 26], log rank p = 0.78). At
      presentation, ARC definite ST (n = 48) and ARC-like definite GO (n = 32) were
      adjudicated to be linked to 4 (8%) and 0 deaths, respectively. At 5 years, ARC
      definite ST (n = 48) and ARC definite/probable ST (n = 75) were associated with
      17 (17 of 48, 35.4%; median days to death: 0 days; interquartile range: 0 to 16
      days; maximum: 321 days) and 31 (31 of 75, 41.3%; median: 0 days; interquartile
      range: 0 to 9 days; maximum: 721 days) cardiac deaths, respectively. At 5 years,
      ARC-like definite GO (n = 32) and ARC-like definite/probable GO (n = 53) were
      associated with 0 and 12 (12 of 52, 23.1%; median: 0 days; interquartile range: 0
      to 14 days; maximum: 257 days) cardiac deaths, respectively. CONCLUSIONS:
      Although the incidence of ST and GO was similar at 5 years, the clinical impact
      of ST appeared greater, with a negative impact on short-term to long-term
      mortality.

PMID- 24140679
TI  - Intra and post-operative complications of esophageal achalasia.
AB  - AIM: To evaluate and discuss all the potential complications affecting morbidity
      of patients treated with surgery for primary achalasia. MATERIAL OF STUDY: A
      review of the available English literature published to date has been conducted.
      All articles reporting surgical experience in achalasia were examined and then
      were selected only those specifically inherent to the topic at issue. RESULTS:
      Mucosal perforation is the main intra-operative complication while persistence or
      recurrence of the disease and gastro-esophageal reflux are those mostly affecting
      patients afterwards, even at long-term follow-up. A few other less common
      morbidities, as well as the technical considerations useful to minimize and
      manage each complication mentioned, are reported. DISCUSSION: Minimally invasive
      surgery for achalasia consent to treat patients with a low rate of perioperative
      complications that can be managed with conservative approach in the majority of
      cases. Risk of esophageal cancer exists in these patients and remains although
      surgical therapy. CONCLUSIONS: Laparoscopic Heller myotomy along with partial
      fundoplication is a safe and effective procedure that should be considered as the
      treatment of choice at first evaluation of achalasic patients rather than
      endoscopic techniques. Robotic technology may add further contribution in
      diminishing perioperative complications.

PMID- 24140678
TI  - Discharge aspirin dose and clinical outcomes in patients with acute coronary
      syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON
      TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing
      platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38).
AB  - OBJECTIVES: The goal of this study was to determine whether there is a
      relationship between aspirin dose and the potent antiplatelet agent prasugrel in
      the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by
      Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial
      Infarction 38) study. BACKGROUND: Optimal aspirin dosing after acute coronary
      syndromes remains uncertain. Previous studies have raised questions regarding an
      interaction between high-dose aspirin and the potent antiplatelet agent
      ticagrelor. METHODS: In TRITON-TIMI 38, we classified 12,674 patients into low
      dose (<150 mg) or high-dose (>=150 mg) aspirin groups based on discharge dose. We
      identified independent correlates of dose selection and studied the impact of
      aspirin dose on the clinical effects of prasugrel. RESULTS: There was significant
      geographical variation in aspirin dosing, with North American patients receiving
      high-dose aspirin more frequently than other countries (66% vs. 28%; p < 0.001).
      Clinical factors correlating with high-dose aspirin included previous
      percutaneous coronary intervention and use of aspirin before randomization.
      Characteristics associated with the use of low-dose aspirin included age >=75
      years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor
      during coronary intervention. Regardless of low- or high-dose aspirin use,
      prasugrel had lower rates of the primary efficacy endpoint (cardiovascular death,
      myocardial infarction, or stroke [CVD/MI/stroke]) (hazard ratio [HR]CVD/MI/stroke
      = 0.78 [95% confidence interval (CI) 0.64 to 0.95] and HRCVD/MI/stroke = 0.87
      [95% CI 0.69 to 1.10], respectively; p value for interaction = 0.48) and higher
      rates of the primary safety endpoint (HR TIMI major bleeding = 1.40 [95% CI 0.81
      to 2.42] and TIMImajor bleeding = 1.30 [95% CI 0.63 to 2.68], respectively; p
      value for interaction = 0.84) compared with clopidogrel. CONCLUSIONS: In TRITON
      TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of
      clopidogrel were directionally consistent regardless of aspirin dose, although
      only the primary efficacy endpoint achieved statistical significance. There was
      no clinically meaningful interaction of aspirin with prasugrel, suggesting that
      previous observations with potent antiplatelet agents indicating differential
      results are not universal. (A Comparison of Prasugrel [CS-747] and Clopidogrel in
      Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary
      Intervention; NCT00097591).

PMID- 24140680
TI  - Probabilistic co-adaptive brain-computer interfacing.
AB  - OBJECTIVE: Brain-computer interfaces (BCIs) are confronted with two fundamental
      challenges: (a) the uncertainty associated with decoding noisy brain signals, and
      (b) the need for co-adaptation between the brain and the interface so as to
      cooperatively achieve a common goal in a task. We seek to mitigate these
      challenges. APPROACH: We introduce a new approach to brain-computer interfacing
      based on partially observable Markov decision processes (POMDPs). POMDPs provide
      a principled approach to handling uncertainty and achieving co-adaptation in the
      following manner: (1) Bayesian inference is used to compute posterior probability
      distributions ('beliefs') over brain and environment state, and (2) actions are
      selected based on entire belief distributions in order to maximize total expected
      reward; by employing methods from reinforcement learning, the POMDP's reward
      function can be updated over time to allow for co-adaptive behaviour. MAIN
      RESULTS: We illustrate our approach using a simple non-invasive BCI which
      optimizes the speed-accuracy trade-off for individual subjects based on the
      signal-to-noise characteristics of their brain signals. We additionally
      demonstrate that the POMDP BCI can automatically detect changes in the user's
      control strategy and can co-adaptively switch control strategies on-the-fly to
      maximize expected reward. SIGNIFICANCE: Our results suggest that the framework of
      POMDPs offers a promising approach for designing BCIs that can handle uncertainty
      in neural signals and co-adapt with the user on an ongoing basis. The fact that
      the POMDP BCI maintains a probability distribution over the user's brain state
      allows a much more powerful form of decision making than traditional BCI
      approaches, which have typically been based on the output of classifiers or
      regression techniques. Furthermore, the co-adaptation of the system allows the
      BCI to make online improvements to its behaviour, adjusting itself automatically
      to the user's changing circumstances.

PMID- 24140681
TI  - Hygienic aspects of livestock manure management and biogas systems operated by
      small-scale pig farmers in Vietnam.
AB  - Biogas digesters are widely promoted and increasingly used to treat and generate
      gas from pig slurry worldwide. The objective of this study was to describe manure
      management practices with focus on biogas digestion among small scale pig farmers
      in Hue (50 farmers) and Hanoi (96 farmers) and to assess fecal contamination
      levels in biogas effluent. Results showed that 84% of the farmers in Hanoi and
      42% in Hue used both pig slurry and human excreta for biogas production. Biogas
      digestion only reduced E. coli concentrations by 1 to 2 log units to 3.70 +/-
      0.84 Escherichia coli (log10) cfu/ml on average in effluent as compared with raw
      slurry. Biogas effluent was commonly used to fertilize vegetables or discharged
      directly into the garden or aquatic recipients. Reduced problems with bad smells
      and flies were reported as main reasons for establishing a biogas digester.
      Further studies are needed to assess human and animal health hazards associated
      with the discharge and use of biogas effluent from small-scale biogas systems.

PMID- 24140682
TI  - Analysis and advanced oxidation treatment of a persistent pharmaceutical compound
      in wastewater and wastewater sludge-carbamazepine.
AB  - Pharmaceutically active compounds (PhACs) are considered as emerging
      environmental problem due to their continuous input and persistence to the
      aquatic ecosystem even at low concentrations. Among them, carbamazepine (CBZ) has
      been detected at the highest frequency, which ends up in aquatic systems via
      wastewater treatment plants (WWTPs) among other sources. The identification and
      quantification of CBZ in wastewater (WW) and wastewater sludge (WWS) is of major
      interest to assess the toxicity of treated effluent discharged into the
      environment. Furthermore, WWS has been subjected for re-use either in
      agricultural application or for the production of value-added products through
      the route of bioconversion. However, this field application is disputable due to
      the presence of these organic compounds and in order to protect the ecosystem or
      end users, data concerning the concentration, fate, behavior as well as the
      perspective of simultaneous degradation of these compounds is urgently necessary.
      Many treatment technologies, including advanced oxidation processes (AOPs) have
      been developed in order to degrade CBZ in WW and WWS. AOPs are technologies based
      on the intermediacy of hydroxyl and other radicals to oxidize recalcitrant, toxic
      and non-biodegradable compounds to various by-products and eventually to inert
      end products. The purpose of this review is to provide information on persistent
      pharmaceutical compound, carbamazepine, its ecological effects and removal during
      various AOPs of WW and WWS. This review also reports the different analytical
      methods available for quantification of CBZ in different contaminated media
      including WW and WWS. 

PMID- 24140683
TI  - Characterization and source apportionment of particulate PAHs in the roadside
      environment in Beijing.
AB  - The profiles of particulate polycyclic aromatic hydrocarbons (PAHs) near a major
      road and relative major sources were determined based on five 1-week intensive
      field campaigns in 2008 and 2009, and the impacts of temporary control measures
      on roadside PAHs during the Beijing Olympics are discussed. The annual average
      concentration of PAHs in the non-Olympic period was 42.3 +/- 52.4 ng/m(3) and
      clear seasonal variation was present. Diesel vehicles, gasoline vehicles and coal
      combustion were identified as the three possible major sources of roadside PAHs
      using positive matrix factorization analysis. During the Olympics, the average
      total PAH concentration decreased to 4.8 +/- 2.7 ng/m(3), which was attributed
      primarily to the reduction of local emissions. Temporary traffic control measures
      significantly changed the diurnal pattern of particulate PAHs at the roadside
      site. Diesel vehicle contribution, in particular, decreased to a negligible
      fraction because heavy-duty diesel vehicles were strictly banned.

PMID- 24140684
TI  - Gulls identified as major source of fecal pollution in coastal waters: a
      microbial source tracking study.
AB  - Gulls were reported as sources of fecal pollution in coastal environments and
      potential vectors of human infections. Microbial source tracking (MST) methods
      were rarely tested to identify this pollution origin. This study was conducted to
      ascertain the source of water fecal contamination in the Berlenga Island,
      Portugal. A total of 169 Escherichia coli isolates from human sewage, 423
      isolates from gull feces and 334 water isolates were analyzed by BOX-PCR. An
      average correct classification of 79.3% was achieved. When an 85% similarity
      cutoff was applied 24% of water isolates were present in gull feces against 2.7%
      detected in sewage. Jackknifing resulted in 29.3% of water isolates classified as
      gull, and 10.8% classified as human. Results indicate that gulls constitute a
      major source of water contamination in the Berlenga Island. This study validated
      a methodology to differentiate human and gull fecal pollution sources in a real
      case of a contaminated beach. 

PMID- 24140685
TI  - Effect of humic acid source on humic acid adsorption onto titanium dioxide
      nanoparticles.
AB  - In many studies, different humic acid (HA) sources are used interchangeably to
      evaluate the effect of organic matter on geochemical processes in the
      environment. This research looks more specifically at the effect of HA source on
      HA adsorption onto nano-TiO2 and how HA adsorption affects the fate and transport
      of nano-TiO2. In this study, six humic acids (HAs) were studied which were
      derived from soils (SLHA), or from sediments (SDHA) all originating from the
      state of Florida. Humic acid adsorption onto titanium dioxide nanoparticles (nano
      TiO2) and the sedimentation of HA-coated and uncoated nano-TiO2 were monitored by
      Ultraviolet-visible (UV-vis) spectroscopy. Synchronous scan fluorescence (SSF)
      spectroscopy was used to complement the study of HA adsorption onto nano-TiO2.
      Phosphate buffer was found to reduce the amount of HA adsorbed onto nano-TiO2
      relative to solutions of NaCl of the same pH and ionic strength. Adsorption
      constant values (Kads) for HAs varied in the order SLHA>FSDHA (freshwater
      sedimentary HA)>ESDHA (estuarine sedimentary HA). SSF results suggested that the
      more highly conjugated fractions of HA, which are more prevalent in SLHAs versus
      SDHAs, were preferentially adsorbed. In order to better understand the
      relationship between adsorption and aggregation, sedimentation studies were
      conducted and it was found that the percentage of nano-TiO2 sedimentation was
      preferentially enhanced in the order of the presence of SLHA>FSDHA>ESDHA. The
      extent of nano-TiO2 sedimentation was decreased with increasing HA concentration.
      TEM imaging of nano-TiO2 confirmed that nano-TiO2 was aggregated in the presence
      of HAs. The findings in this study suggest that HAs from different sources
      influence the fate and transport of nano-TiO2 in the environment differently. 

PMID- 24140686
TI  - Occurrence and exposure evaluation of perchlorate in outdoor dust and soil in
      mainland China.
AB  - A total of 98 paired soil and outdoor dust samples were collected across mainland
      China for survey of perchlorate. Perchlorate was detected in all of the soil and
      outdoor dust samples. High levels of perchlorate were found in soil, ranging from
      0.001 to 216 mg/kg in Northern China and from 0.001 to 25.8 mg/kg in Southern
      China. Even higher perchlorate concentrations were detected in dust samples, with
      concentrations ranging from 0.132 to 5,300 mg/kg in Northern China, and from
      0.270 to 3,700 mg/kg in Southern China. This is the first known report of
      perchlorate in dust samples. The high perchlorate levels in soil and dust may
      raise concern on the potential risk for organisms and human. The daily
      perchlorate intakes were evaluated based on our measured perchlorate
      concentrations via inhalation, ingestion, and dermal contact of soil and dust for
      both children and adults, respectively. In general, the exposure from soil does
      not appear to lead to perchlorate intakes exceeding the US EPA reference for both
      children and adults. However, children can be at risk from exposure to
      perchlorate via dust, and it needs considerable concern for both children and
      adults at the sites with high dust perchlorate concentrations. After comparison
      with other possible exposure pathways, such as from drinking water, we suggested
      that dust may be an important potential source of perchlorate exposure in China,
      and further study is needed, especially for indoor dust.

PMID- 24140687
TI  - Glutathione S-transferase, glutathione peroxidase and acetylcholinesterase
      activities in mussels transplanted to harbour areas.
AB  - As part of an integrative monitoring campaign involving water and sediment
      chemistry, in situ bioassays, and mussel bioaccumulation and biomarkers, Mytilus
      galloprovincialis mussels of standard size were transplanted from a clean
      location to five sites in two important harbours from the Atlantic coast of Spain
      (Vigo and Pasaia). After a 30-day field exposure, the concentrations of major
      contaminants (trace metals, polychlorinated biphenyls and polycyclic aromatic
      hydrocarbons) accumulated in mussel tissues were measured at each site, and a
      mussel bioaccumulation index (MBI) was calculated. The enzymatic activity levels
      of glutathione S-transferase (GST), glutathione peroxidase (GPx) and
      acetylcholinesterase (AChE) were quantified in the gills of transplanted mussels
      (n=12). Mussels from the most polluted sites consistently exhibited significantly
      higher GST and GPx activities compared to the control site, whereas AChE activity
      was significantly inhibited. The responses of the GST and GPx activities were
      related to MBI, trace metals and PAH concentrations in mussels, whereas AChE
      activity was related to the trace metals concentrations in mussels. The above
      results suggest that GST and AChE activities can be used as potential biomarkers
      for active monitoring in marine coastal ecosystems. However, at this moment, GPx
      activity is not robust enough to be applicable to harbour areas. 

PMID- 24140688
TI  - Occurrence and sources of polar lipid tracers in sediments from the Shatt al-Arab
      River of Iraq and the northwestern Arabian Gulf.
AB  - Shallow surface sediment samples from the southern part of the Shatt al-Arab
      River estuary of Iraq and the northwestern Arabian Gulf were analyzed for polar
      lipid compounds including n-alkanoic acids, n-alkanols, steroids and
      triterpenoids. The results showed that the n-alkanoic acids, methyl n-alkanoates
      and n-alkanols typically ranged from C12 to C32 with total concentrations of 3.2
      to 108.2 MUg g(-1)dwt sample, from C12 to C30 with totals of 1.1 to 18.9 MUg g(
      1)dwt sample, and from C14 to C32 at 1.8 to 112.6 MUg g(-1)dwt sample,
      respectively. Steroids and triterpenoids were detected and included stenols,
      stanols, stenones, stanones, tetrahymanol, tetrahymanone and extended betabeta
      hopanes. The total steroid concentrations ranged from 2.8 to 78.4 MUg g(-1)dwt
      sample, whereas the triterpenoids varied from 0.05 to 7.6 MUg g(-1)dwt sample.
      The simple regression analysis of the results and the spatial distribution
      patterns of the identified organic tracers indicated that the inter-compound
      relationships were related mainly to their major sources. Cluster analysis and
      principal component analysis (PCA) of data set showed that the sampling sites are
      similar. These sources were allochthonous (terrestrial vegetation), autochthonous
      (plankton residues and bacteria in the sediments) and anthropogenic (sewage and
      petroleum).

PMID- 24140689
TI  - Influence of carbohydrate addition on nitrogen transformations and greenhouse gas
      emissions of intensive aquaculture system.
AB  - Aquaculture is one of the fastest-growing segments of the food economy in modern
      times. It is also being considered as an important source of greenhouse gas (GHG)
      emissions. To date, limited studies have been conducted on GHG emissions from
      aquaculture system. In this study, daily addition of fish feed and soluble starch
      at a carbon-to-nitrogen (C/N) ratio of 16:1 (w/w) was used to examine the effects
      of carbohydrate addition on nitrogen transformations and GHG emissions in a zero
      water exchange intensive aquaculture system. The addition of soluble starch
      stimulated heterotrophic bacterial growth and denitrification, which led to lower
      total ammonia nitrogen, nitrite and nitrate concentrations in aqueous phase.
      About 76.2% of the nitrogen output was emitted in the form of gaseous nitrogen
      (i.e., N2 and N2O) in the treatment tank (i.e., aquaculture tank with soluble
      starch addition), while gaseous nitrogen accounted for 33.3% of the nitrogen
      output in the control tank (i.e., aquaculture tank without soluble starch
      addition). Although soluble starch addition reduced daily N2O emissions by 83.4%,
      it resulted in an increase of daily carbon dioxide (CO2) emissions by 91.1%.
      Overall, starch addition did not contribute to controlling the GHG emissions from
      the aquaculture system. 

PMID- 24140690
TI  - Influence of hydrophobic/hydrophilic fractions of extracellular organic matters
      of Microcystis aeruginosa on ultrafiltration membrane fouling.
AB  - Fouling is a major obstacle to maintain the efficiency of ultrafiltration-based
      drinking water treatment process. Algal extracellular organic matters (EOMs) are
      currently considered as one of the major sources of membrane fouling. The
      objective of this study was to investigate the influence of different
      hydrophobic/hydrophilic fractions of EOM extracted from Microcystis aeruginosa on
      ultrafiltration membrane fouling at lab scale. The experimental data indicated
      that EOM exhibited similar flux decline trends on polyethersulfone (PES) and
      regenerated cellulose (RC) membranes but caused greater irreversible fouling on
      PES membrane than RC membrane due to its hydrophobic property. It was also
      observed that charged hydrophilic (CHPI) and neutral hydrophilic (NHPI) fractions
      caused greater flux decline over hydrophobic (HPO) and transphilic (TPI)
      fractions. For PES membrane, the order of the irreversible fouling potentials for
      the four fractions was HPO>TPI>CHPI>NHPI, while the irreversible fouling
      potentials of RC membrane were tiny and could be ignored. Fluorescence excitation
      emission matrix (EEM) spectra and Fourier transform infrared (FTIR) spectra
      suggested that protein-like, polysaccharide-like and humic-like substances were
      the major components responsible for membrane fouling. The results also indicated
      that the irreversible fouling increased as the pH decreased. The addition of
      calcium to feed solutions led to more severe flux decline and irreversible
      fouling. 

PMID- 24140691
TI  - Behavioural, physiological and biochemical markers in damselfly larvae (Ischnura
      elegans) to assess effects of accumulated metal mixtures.
AB  - Currently it is not known at which organismal level effects of metal mixtures in
      nature can best be detected, which is relevant to develop accurate monitoring
      schemes and quality standards. The present study investigated relationships
      between accumulated metals with different levels of biological organisation in
      the aquatic larval stage of the damselfly Ischnura elegans. Larvae were collected
      in seven Flemish ponds differing in metal load. In each field-collected larva we
      quantified concentrations of accumulated metals and a set of biochemical markers
      (acetylcholinesterase (AChE) and glutathione-S-transferase (GST)), physiological
      endpoints (energy storage), and behavioural responses (locomotory activity and
      the feeding rate). Accumulated metal levels and the measured endpoints
      significantly differed among ponds, however, a large variation in metal load
      index was observed within individuals of the same population. Only GST and energy
      availability could be partly predicted by the observed variation in metal load
      index on individual damselfly level. However, no single endpoint could be used to
      detect the observed variation in metal load index among populations. In
      conclusion, the sublethal endpoints cannot be used as reliable biomarkers to
      monitor the toxicity of accumulated metal mixtures in natural populations of I.
      elegans. 

PMID- 24140692
TI  - Nitrogen deposition and exceedance of critical loads for nutrient nitrogen in
      Irish grasslands.
AB  - High resolution nitrogen (N) deposition maps were developed to assess the
      exceedance of empirical critical loads of nutrient N for grasslands in Ireland.
      Nitrogen emissions have remained relatively constant during the past 20 yrs and
      are projected to remain constant under current legislation. Total N deposition
      (estimated as wet nitrate [NO3(-)] and ammonium [NH4(+)] plus dry NO* and NH3)
      ranged from 2 to 22 kg Nha(-1)yr(-1) (mean=12 kg Nha(-1)yr(-1)) to grasslands.
      Empirical critical loads for nutrient N were set at 15 kg Nha(-1)yr(-1) for both
      acid and calcareous grasslands; exceedance was observed for ~35% (~2,311 km(2))
      of mapped acid grasslands. In contrast, only ~9% of calcareous grasslands (~35
      km(2)) received N deposition in excess of the critical load. Reduced N deposition
      (primarily dry NH3) represented the dominant form to grasslands (range 55-90%)
      owing to significant emissions associated with livestock (primarily cattle). The
      extent of exceedance in acid grasslands suggests that N deposition to this
      habitat type may lead to adverse impacts such as a decline in plant species
      diversity and soil acidification. Further, given that elevated N deposition was
      dominated by NH3 associated with agricultural emissions rather than long-range
      transboundary sources, future improvements in air quality need to be driven by
      national policies.

PMID- 24140693
TI  - Cadmium exposure and its health effects: a 19-year follow-up study of a polluted
      area in China.
AB  - BACKGROUND: Dayu County, which is located in southwestern Jiangxi Province in
      China, has been a cadmium (Cd)-contaminated area since the 1960s. A series of
      studies about Cd pollution were carried out in the 1980s. However, no further
      studies of the area were conducted during the following 19 years. AIM: To observe
      cadmium (Cd) exposure levels and its health risks among residents living in
      contaminated areas that have been exposed to environmental cadmium pollution for
      45 years. METHODS: Subjects involved in the survey in 1987 were interviewed again
      in 2006. Rice and urine samples from surviving subjects were collected to assess
      the level of cadmium exposure. Urinary Cd (U-Cd), urinary beta2-microglobulin (U
      beta2-M) and urinary N-acetyl-beta-d-glucosaminidase (U-NAG) were used as
      biomarkers to evaluate renal function. A medical examination was also performed
      on all subjects to diagnose clinical symptoms of Cd-exposure. RESULT: Of the 96
      subjects of the 1987 study who were alive in 2006, a total of 76 subjects were
      successfully recruited to this study. The average cadmium concentration in rice
      from the exposed areas was 0.59 +/- 0.41 mg/kg in 2006, the average concentration
      of U-Cd, U-beta2-M and U-NAG from cadmium-exposed areas was 25.82 +/- 0.20 MUg/g
      Cr, 6525.71 +/- 0.93 MUg/g Cr and 13.65 +/- 0.24 MUmol/g Cr, respectively, in
      2006. Compared with the 1987 results, the 2006 results showed that the U-beta2-M
      level in the exposed areas increased significantly after 19 years (p<0.05). The
      levels of U-Cd and U-NAG did not significantly change over time. CONCLUSION: The
      concentration of Cd in polluted areas in 2006 is higher than it was in 1987.
      Renal dysfunction has worsened after 45 years of continuous exposure. Thus,
      environmental protection and special procedures to remove cadmium in these areas
      require urgent consideration.

PMID- 24140694
TI  - Categorical Indicator Kriging for assessing the risk of groundwater nitrate
      pollution: the case of Vega de Granada aquifer (SE Spain).
AB  - Groundwater nitrate pollution associated with agricultural activity is an
      important environmental problem in the management of this natural resource, as
      acknowledged by the European Water Framework Directive. Therefore, specific
      measures aimed to control the risk of water pollution by nitrates must be
      implemented to minimise its impact on the environment and potential risk to human
      health. The spatial probability distribution of nitrate contents exceeding a
      threshold or limit value, established within the quality standard, will be
      helpful to managers and decision-makers. A methodology based on non-parametric
      and non-linear methods of Indicator Kriging was used in the elaboration of a
      nitrate pollution categorical map for the aquifer of Vega de Granada (SE Spain).
      The map has been obtained from the local estimation of the probability that a
      nitrate content in an unsampled location belongs to one of the three categories
      established by the European Water Framework Directive: CL. 1 good quality [Min -
      37.5 ppm], CL. 2 intermediate quality [37.5-50 ppm] and CL. 3 poor quality [50
      ppm - Max]. The obtained results show that the areas exceeding nitrate
      concentrations of 50 ppm, poor quality waters, occupy more than 50% of the
      aquifer area. A great proportion of the area's municipalities are located in
      these poor quality water areas. The intermediate quality and good quality areas
      correspond to 21% and 28%, respectively, but with the highest population density.
      These results are coherent with the experimental data, which show an average
      nitrate concentration value of 72 ppm, significantly higher than the quality
      standard limit of 50 ppm. Consequently, the results suggest the importance of
      planning actions in order to control and monitor aquifer nitrate pollution.

PMID- 24140695
TI  - Integument colouration in relation to persistent organic pollutants and body
      condition in arctic breeding black-legged kittiwakes (Rissa tridactyla).
AB  - Vertebrates cannot synthetize carotenoids de novo but have to acquire them
      through their diet. In birds, carotenoids are responsible for the yellow to red
      colouration of many secondary sexual traits. They are also involved in
      physiological functions such as immunostimulation and immunoregulation.
      Consequently, carotenoid-based colouration is very often considered as a reliable
      signal for health and foraging abilities. Although a few studies have suggested
      that carotenoid-based coloured traits could be sensitive to environmental
      pollution such as persistent organic pollutants (POPs) contamination, the
      relationships between pollutants and colouration remain unclear. Here, we
      examined the relationships between the colouration of carotenoid-based
      integuments and individual POP levels in pre-laying female black-legged
      kittiwakes from very high latitudes. In this area, these arctic seabirds are
      exposed to high POPs contamination. Additionally, we investigated the
      relationships between colouration and body condition, a frequently used index of
      individual quality. We found a negative relationship between POP levels and
      several components of integument colouration: saturation of eye-ring, gapes and
      tongue, suggesting that POPs could disrupt colouration of labile integuments in
      female kittiwakes. In addition, we found that females in better body condition
      displayed more orange and brighter gapes and tongue than females in poor body
      condition. These results demonstrate that hue and brightness are sensitive to the
      current health and nutritional status of female kittiwakes. Overall, our study
      shows that carotenoid-based colour integuments can be affected by several
      environmental-driven variables. 

PMID- 24140696
TI  - Integrating quantitative PCR and Bayesian statistics in quantifying human
      adenoviruses in small volumes of source water.
AB  - Rapid quantification of viral pathogens in drinking and recreational water can
      help reduce waterborne disease risks. For this purpose, samples in small volume
      (e.g. 1L) are favored because of the convenience of collection, transportation
      and processing. However, the results of viral analysis are often subject to
      uncertainty. To overcome this limitation, we propose an approach that integrates
      Bayesian statistics, efficient concentration methods, and quantitative PCR (qPCR)
      to quantify viral pathogens in water. Using this approach, we quantified human
      adenoviruses (HAdVs) in eighteen samples of source water collected from six
      drinking water treatment plants. HAdVs were found in seven samples. In the other
      eleven samples, HAdVs were not detected by qPCR, but might have existed based on
      Bayesian inference. Our integrated approach that quantifies uncertainty provides
      a better understanding than conventional assessments of potential risks to public
      health, particularly in cases when pathogens may present a threat but cannot be
      detected by traditional methods. 

PMID- 24140697
TI  - Application of fully automatic hollow fiber liquid phase microextraction to
      assess the distribution of organophosphate esters in the Pearl River Estuaries.
AB  - Organophosphate esters (OPEs) are widespread organic pollutants that could be
      detected in various environmental matrices. In this study, a sample pretreatment
      method was developed for the determination of 9 OPEs by automatic hollow fiber
      liquid phase microextraction (HF-LPME) coupled with gas chromatography-mass
      spectrometry (GC-MS). High sensitivity of OPEs could be achieved after
      optimization of several important parameters with the limits of detection (LODs)
      ranging from 2.6 to 120 ng L(-1) for different individual OPEs, and the relative
      standard deviations (RSDs) ranged from 2.1% to 10.4%. Acceptable recoveries were
      observed and the proposed method was then successfully applied to determine OPEs
      in seawaters collected from 23 sampling sites of the Pearl River Estuaries in dry
      and wet seasons, respectively. All of the OPEs could be detected, except tris(2
      ethylhexyl) phosphate (TEHP). The total concentrations of 9 OPEs in seawaters
      were ranging from 2.04 (Hemen) to 3.12 (Humen) MUg L(-1) in the dry season and
      from 1.08 (Hemen) to 2.50 (Jitimen) MUgL(-1) in the wet season. By using spatial
      interpolation method of ordinary kriging, the most polluted area of SigmaOPEs was
      found in Humen in the dry season, while it was Jitimen in the wet season.
      Moreover, the annual input of SigmaOPEs discharged via eight estuaries ranged
      from 384 tons (Jitimen) to 1,225 tons (Modaomen), and the total annual input was
      5,694 tons.

PMID- 24140698
TI  - Simulated air quality and pollutant budgets over Europe in 2008.
AB  - Major gaseous and particulate pollutant levels over Europe in 2008 have been
      simulated using the offline-coupled WRFCMAQ chemistry and transport modeling
      system. The simulations are compared with surface observations from the EMEP
      stations, ozone (O3) soundings, ship-borne O3 and nitrogen dioxide (NO2)
      observations in the western Mediterranean, tropospheric NO2 vertical column
      densities from the SCIAMACHY instrument, and aerosol optical depths (AOD) from
      the AERONET. The results show that on average, surface O3 levels are
      underestimated by 4 to 7% over the northern European EMEP stations while they are
      overestimated by 7-10% over the southern European EMEP stations and
      underestimated in the tropospheric column (by 10-20%). Particulate matter (PM)
      mass concentrations are underestimated by up to 60%, particularly in southern and
      eastern Europe, suggesting underestimated PM sources. Larger differences are
      calculated for individual aerosol components, particularly for organic and
      elemental carbon than for the total PM mass, indicating uncertainty in the
      combustion sources. Better agreement has been obtained for aerosol species over
      urban areas of the eastern Mediterranean, particularly for nss-SO4(2), attributed
      to the implementation of higher quality emission inventories for that area.
      Simulated AOD levels are lower than the AERONET observations by 10% on average,
      with average underestimations of 3% north of 40 degrees N, attributed to the low
      anthropogenic emissions in the model and 22% south of 40 degrees N, suggesting
      underestimated natural and resuspended dust emissions. Overall, the results
      reveal differences in the model performance between northern and southern Europe,
      suggesting significant differences in the representation of both anthropogenic
      and natural emissions in these regions. Budget analyses indicate that O3 and
      peroxyacetyl nitrate (PAN) are transported from the free troposphere (FT) to the
      planetary boundary layer over Europe, while other species follow the reverse path
      and are then advected away from the source region. 

PMID- 24140699
TI  - Dermal & inhalation exposure of operators during fungicide application in
      vineyards. Evaluation of coverall performance.
AB  - In the present study the dermal and the inhalation exposure of five operators
      during fungicide applications in vineyards were determined. The produced exposure
      datasets can be used as surrogate for the estimation of the actual and the
      potential dermal as well as inhalation operator exposure levels for this
      application scenario. The dermal exposure was measured using the whole body
      dosimetry method while the inhalation exposure with the use of personal air
      sampling devices with XAD tubes located on the operator's breathing zone. Ten
      field trials were carried out by 5 different operators using a tractor assisted
      hand-held lance with spray gun at the Tanagra region of Viotia, Greece. An in
      house GC-ECD analytical method was developed and validated for the determination
      of penconazole, which was the active substance (a.s.) of the fungicide
      formulation used in field trials. The mean recovery of field-fortified samples
      was 81%. The operator exposure results showed expected variability and were
      compared to those derived from the German model for prediction of operator
      exposure. The comparison of the 75th percentile values for an operator wearing
      personal protection equipment has shown that the measured levels were 2.2 times
      lower than those estimated by the German model. The levels of actual dermal
      exposure ranged from 2 to 19 mg/kg a.s. applied. The protection provided by the
      two types of coveralls was evaluated and in comparison to the existing reduction
      factors used for other types of PPE (coveralls) was found satisfactory for the
      operator under the conditions of the specific applications.

PMID- 24140700
TI  - Oxidative stress effects of titanium dioxide nanoparticle aggregates in zebrafish
      embryos.
AB  - There is limited data on the sub-lethal oxidative stress effects of titanium
      dioxide nanoparticle aggregates (NM-TiO2) and its modulation by simulated solar
      radiation (SSR) to aquatic organisms. This study aimed to examine sublethal
      oxidative stress effects of aqueous exposure to three different types of NM-TiO2
      differing in their coating or crystal structure but of similar primary size (20
      nm) plus a micron-sized bulk material to zebrafish embryos without and with SSR.
      Oxidative stress responses of known model prooxidant (tert-Butyl hydroperoxide)
      and photoprooxidant (fluoranthene) compounds were also studied. Results evidenced
      a low bio-availability of NM-TiO2 to embryos with detrimental effects on growth
      at 1 mg ml(-1). Phototoxicity increased moderately, by 3 and 1.5 fold, under co
      exposures to fluoranthene (100 MUgl(-1)) and to the NM-TiO2 P25 (1 mg ml(-1)),
      respectively, being unchanged in the other TiO2 aggregates. In vitro exposures
      under SSR confirmed that the NM-TiO2 P25 had the highest potential to generate
      reactive oxygen species (ROS). Antioxidant enzyme activities of superoxide
      dismutase increased shortly after exposure to the studied materials, whereas the
      levels of glutathione tend to be altered after longer exposures. All compounds
      were able to produce oxidative stress enhancing the senescence-associated beta
      galactosidase pigment (SA-beta-gal). Under SSR radiation the NM-TiO2 P25 affected
      antioxidant and oxidative stress responses as the phototoxic compound
      fluoranthene. These results indicated that despite the low bio-availability of NM
      TiO2 to zebrafish embryos, P25 was phototoxic due to the production of reactive
      oxygen species. Nevertheless, overall our results indicated that fish development
      may not be at high risk in the face of NM-TiO2, even when combined with
      prooxidant conditions.

PMID- 24140701
TI  - Brominated flame retardants and perfluoroalkyl substances in sediments from the
      Czech aquatic ecosystem.
AB  - This study reports results of analysis of various groups of halogenated
      chemicals, including brominated flame retardants (BFRs), such as polybrominated
      diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDs), tetrabromobisphenol A
      (TBBPA) and perfluoroalkyl substances (PFASs) in 31 sediment samples collected in
      different localities of the Czech Republic. In this survey, identification of
      potential sources of these compounds was also performed; therefore several
      sampling sites located in highly industrialized areas were involved.
      Concentrations of target groups of analytes determined in sediments from several
      Czech rivers examined within this study decreased in the following order:
      decabromodiphenyl ether (BDE 209) >>> TBBPA~HBCDs~linear perfluorooctane
      sulfonate (L-PFOS)>other PBDEs~perfluorinated carboxylic acids
      (PFCAs)~perfluorooctane sulfonamide (FOSA). When compared the contamination by
      two monitored groups of halogenated compounds, the total content of ?BFRs was
      significantly higher, i.e. in the range from the method quantification limit
      (MQL) to 528 MUg/kg dry weight (dw) (median value 5.68 MUg/kg dw), than the total
      concentration of ?PFASs, that was in the range from MQL to 25.5 MUg/kg dw (median
      value 1.48 MUg/kg dw). The extremely highest content of BFR group (265-528 MUg/kg
      dw) was found in sediments collected in sampling sites on the Labe and Luzicka
      Nisa Rivers, which are located in highly chemical industrialized areas and also
      in the sample from the locality Lampertice obtained from the sedimentation tank
      close to the factory processing and storing waste. These concentrations were a
      little bit higher or comparable to those found in similar highly industrialized
      areas worldwide.

PMID- 24140702
TI  - Historical occurrences of polybrominated diphenyl ethers and polychlorinated
      biphenyls in Manila Bay, Philippines, and in the upper Gulf of Thailand.
AB  - Historical trends of the accumulation of polybrominated diphenyl ethers (PBDEs)
      and polychlorinated biphenyls (PCBs) in a typical tropical Asian environment were
      investigated using radio-dated sediment cores from Manila Bay, the Philippines
      and from the upper Gulf of Thailand. Vertical profiles indicated earlier usage of
      PCBs than of PBDEs which coincided with their industrial production. The
      increasing concentrations of total PBDEs and PCBs toward the surface suggested an
      increased consumption of PBDEs; and possible leakage of PCBs from old machineries
      into the aquatic environment in recent years. Current input of PCBs to the
      catchment of Manila Bay was supported by the analyses of air samples and plastic
      resin pellets. The vertical profiles of total PBDEs in the cores (i.e., rapidly
      increasing concentrations corresponding to the mid-1980s until mid-1990s,
      followed by a decrease until the early 2000s, and increasing again toward the
      surface) likely corresponded to the rapid economic growth in Asia in the 1990s,
      the Asian financial crisis in 1997, and the economic recovery since early 2000s.
      BDE-209 was predominant especially on the surface layers. BDEs 47 and 99
      generally decreased toward the surface, reflecting the phase-out of the technical
      penta-PBDE products and the regulation by the Stockholm Convention in recent
      years. Increasing ratios of BDE-202/209, 206/209, 207/209 and decreasing % of BDE
      209 down the core layers may provide evidence for the anaerobic debromination of
      BDE-209 in the sediment cores. Inventories in ng/cm(2) of total PCBs were higher
      than total PBDEs (92 vs. 34 and 47 vs. 11 in the Philippines; 47 vs. 33 in
      Thailand). However, the doubling times indicated faster accumulation of total
      PBDEs (6-7 years) and BDE-209 (6-7.5 years) than of PCBs (8-11 years).
      Furthermore, the temporal increase in BDE-209 was comparable to or faster than
      those reported in other water bodies around the world.

PMID- 24140703
TI  - Community-based participatory research with indigenous communities: the proximity
      paradox.
AB  - Community-based participatory research (CBPR) is a promising approach used with
      increasing prevalence in health research with underserviced Indigenous
      communities in rural and remote locations. This case comparison used CBPR
      principles to examine the characteristics of two collaborative research projects
      in Canada. Both projects reflected CBPR principles in unique ways with particular
      differences related to community access and proximity of collaborating partners.
      CBPR principles are often used and recommended for partnerships involving remote
      underserviced communities, however many of these principles were easier to follow
      for the collaboration with a relatively well serviced community in close
      proximity to researchers, and more challenging to follow for a remote
      underserviced community. The proximity paradox is an apparent contradiction in
      the increasing application of CBPR principles for use in distal partnerships with
      remote Indigenous communities when many of these same principles are nearly
      impossible to follow. CBPR principles are much easier to apply in proximal
      partnerships because they afford an environment where collaborative relationships
      can be developed and sustained. 

PMID- 24140704
TI  - Green spaces and pregnancy outcomes in Southern California.
AB  - Little is known about the impacts of green spaces on pregnancy outcomes. The
      relationship between green space exposure and preeclampsia has never been
      studied. We used a hospital-based perinatal database including more than 80,000
      births to study the relationships between greenness exposure and three pregnancy
      outcomes: birth weight in term born infants, preterm deliveries and preeclampsia.
      Greenness was characterized using the normalized difference vegetation index
      (NDVI) within circular buffers surrounding maternal homes. Analyses were
      conducted using generalized estimating equations, adjusted for potential
      confounders. We observed an increase in birth weight in term born infants and a
      reduced risk of preterm births associated with an increase in NDVI. No
      significant association was observed between greenness and preeclampsia. This
      study provides modest support for beneficial effects of greenness exposure on
      pregnancy outcomes and calls for confirmation in other study settings. 

PMID- 24140705
TI  - Glucose transporter 1 expression accompanies hypoxia sensing in the cyclic canine
      corpus luteum.
AB  - The canine corpus luteum (CL) functions as a source of progesterone (P4) and
      17beta-oestradiol (E2); however, the transport of energy substrates to maintain
      its high hormonal output has not yet been characterised. This study involved the
      localisation and temporal distribution of the facilitative glucose transporter 1
      and the quantification of the corresponding protein (GLUT1) and gene (SLC2A1)
      expression. Some GLUT1/SLC2A1 regulatory proteins, such as hypoxia-inducible
      factor 1alpha (HIF1A) and fibroblast growth factor 2 (FGF2); mRNAs, such as
      HIF1A, FGF2 and vascular endothelial growth factor A (VEGFA); and VEGFA receptors
      1 and 2 (FLT1 and KDR) were also analysed from days 10 to 70 after ovulation.
      Additionally, plasma P4 and E2 levels were assessed via chemiluminescence.
      Moreover, the canine KDR sequence has been cloned, thereby enabling subsequent
      semi-quantitative PCR analysis. Our results demonstrate time-dependent variations
      in the expression profile of SLC2A1 during dioestrus, which were accompanied by
      highly correlated changes (0.84<r<0.98; P<0.03) in the gene expression of HIF1A,
      VEGF and FLT1 as well as in P4 plasma concentrations. FGF2 mRNA correlated with
      E2 plasma concentrations (r=0.61; P=0.01). Our data reveal that the glucose
      transporter is regulated throughout the CL lifespan and suggest that CL depends
      on the sensing of hypoxia and the status of luteal vascularisation. Moreover,
      time-dependent expression of GLUT1/SLC2A1 may lie underneath increased metabolic
      and energetic requirements for sustaining P4 production. 

PMID- 24140706
TI  - Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor
      negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic
      regulation.
AB  - This study investigates the anticancer effect of arctigenin (ATG), a natural
      lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells.
      Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis
      in vitro and in vivo. ATG triggers the mitochondrial caspase-independent
      pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG
      nuclear translocation. ATG increased cellular reactive oxygen species (ROS)
      production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing
      glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK
      and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen
      peroxide scavenger, significantly decreases ATG-mediated p38 activation and
      apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2
      downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription
      factor activated by p38, and then upregulates histone H3K9 trimethylation in the
      Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together,
      the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the
      ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of
      histone H3K9 trimethylation. 

PMID- 24140707
TI  - Elongation factor 2 diphthamide is critical for translation of two IRES-dependent
      protein targets, XIAP and FGF2, under oxidative stress conditions.
AB  - Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA.
      A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role
      for eEF2 in the cellular stress response is highlighted by the fact that eEF2 is
      sensitive to oxidative stress and that it must be active to drive the synthesis
      of proteins that help cells to mitigate the adverse effects of oxidative stress.
      Many of these proteins are encoded by mRNAs containing a sequence called an
      "internal ribosomal entry site" (IRES). Under high oxidative stress conditions
      diphthamide-deficient cells were significantly more sensitive to cell death.
      These results suggest that diphthamide may play a role in protection against the
      degradation of eEF2. This protection is especially important in those situations
      in which eEF2 is necessary for the reprogramming of translation from global to
      IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of
      apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized
      from mRNAs with IRESs that promote cell survival, is deregulated in diphthamide
      deficient cells. Our findings therefore suggest that eEF2 diphthamide controls
      the selective translation of IRES-dependent protein targets XIAP and FGF2,
      critical for cell survival under conditions of oxidative stress. 

PMID- 24140708
TI  - Poly(ADP-ribose) polymerase-1 modulates Nrf2-dependent transcription.
AB  - The basic leucine zipper transcription factor Nrf2 has emerged as a master
      regulator of intracellular redox homeostasis by controlling the expression of a
      battery of redox-balancing antioxidants and phase II detoxification enzymes.
      Under oxidative stress conditions, Nrf2 is induced at the protein level through
      redox-sensitive modifications on critical cysteine residues in Keap1, a component
      of an E3 ubiquitin ligase complex that targets Nrf2 for proteasomal degradation.
      Poly(ADP-ribose) polymerase-1 (PARP-1) is historically known to function in DNA
      damage detection and repair; however, recently PARP-1 has been shown to play an
      important role in other biochemical activities, such as DNA methylation and
      imprinting, insulator activity, chromosome organization, and transcriptional
      regulation. The exact role of PARP-1 in transcription modulation and the
      underlying mechanisms remain poorly defined. In this study, we report that PARP-1
      forms complexes with the antioxidant response element (ARE) within the promoter
      region of Nrf2 target genes and upregulates the transcriptional activity of Nrf2.
      Interestingly, PARP-1 neither physically interacts with Nrf2 nor promotes the
      expression of Nrf2. In addition, PARP-1 does not target Nrf2 for poly(ADP
      ribosyl)ation. Instead, PARP-1 interacts directly with small Maf proteins and the
      ARE of Nrf2 target genes, which augments ARE-specific DNA-binding of Nrf2 and
      enhances the transcription of Nrf2 target genes. Collectively, these results
      suggest that PARP-1 serves as a transcriptional coactivator, upregulating the
      transcriptional activity of Nrf2 by enhancing the interaction among Nrf2, MafG,
      and the ARE. 

PMID- 24140709
TI  - Antioxidants: GRABbing new headlines.

PMID- 24140710
TI  - Faecal cortisol metabolites in Bengal (Panthera tigris tigris) and Sumatran
      tigers (Panthera tigris sumatrae).
AB  - The tiger (Panthera tigris) faces a great risk of extinction as its wild numbers
      have plummeted due to poaching and habitat destruction so ex-situ conservation
      programs are becoming ever more necessary. Reliable non-invasive biomarkers of
      the stress hormone (cortisol) are necessary for assessing the health and welfare
      of tigers in captivity. To our knowledge, non-invasive stress endocrinology
      methods have not been tested as widely in tigers. The first aim of this study was
      to describe and validate a faecal cortisol metabolite enzyme-immmunoassay (FCM
      EIA) for two tiger sub-species, the Bengal tiger (Panthera tigris tigris) and the
      Sumatran tiger (Panthera tigris sumatrae). Individual tigers (n=22) were studied
      in two large Zoos in Queensland, Australia (Dreamworld Theme Park and Australia
      Zoo). Fresh faecal samples (<12 h old) were collected each morning from both Zoos
      over a study period of 21 days. Biological validation was conducted separately by
      collecting feces 5 days before and 5 days after blood was taken from four male
      and five female tigers. Results showed that mean FCM levels increased by 138% and
      285% in the male and female tigers within 1 day after bloods were taken,
      returning to baseline in 5 days. Laboratory validations of the FCM EIA were done
      using an extraction efficiency test and parallelism. Results showed >89% recovery
      of the cortisol standard that was added to tiger faecal extract. We also obtained
      parallel displacement of the serially diluted cortisol standard against serially
      diluted tiger faecal extract. Our second aim was to determine whether the FCM
      levels were significantly different between tiger sub-species and sex. Results
      showed no significant difference in mean FCM levels between the Bengal and
      Sumatran tiger sub-species. Mean levels of FCMs were significantly higher in
      females than in male tigers. Those male and female tigers with reported health
      issues during the study period expressed higher FCM levels than the reportedly
      healthy tigers. Interestingly, those tigers that took part in some activity (such
      as walks, photos, presentations and guest feeds) expressed moderately higher FCM
      levels at Dreamworld and lower FCM levels at Australia Zoo in comparison to those
      tigers that did not take part in such activities. These results indicate
      potential habituation in some tigers for routine activity through specialized
      training and pre-conditioning. In conclusion, the FCM EIA described in this study
      provides a reliable non-invasive method for evaluating the stress status of
      tigers in Zoos.

PMID- 24140711
TI  - Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin
      resistance in male mice.
AB  - Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed
      in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD)
      feeding induces the robust increase of circulating THBS1 in the early stages of
      HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain
      and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has
      demonstrated that Thbs1-null mice are protected from HFD-induced insulin
      resistance. Tissue-specific glucose uptake study has revealed that the insulin
      sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles.
      Further assessments of the muscle phenotype using RNA sequencing, quantitative
      PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles
      are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with
      a new collagen deposition. At the same time, the Thbs1-null mice display a better
      circadian rhythm and higher amplitude of energy expenditure with a browning
      phenotype in sc adipose tissues. These results suggest that THBS1, which
      circulates in response to a HFD, may induce insulin resistance and fibrotic
      tissue damage in skeletal muscles as well as the de-browning of sc adipose
      tissues in the early stages of a HFD challenge. Our study may shed new light on
      the pathogenic role played by a circulating extracellular matrix protein in the
      cross talk between adipose tissues and skeletal muscles during obesity
      progression. 

PMID- 24140712
TI  - Molecular mechanisms underlying the rapid arrhythmogenic action of bisphenol A in
      female rat hearts.
AB  - Previously we showed that bisphenol A (BPA), an environmental estrogenic
      endocrine disruptor, rapidly altered Ca(2+) handling and promoted arrhythmias in
      female rat hearts. The underlying molecular mechanism was not known. Here we
      examined the cardiac-specific signaling mechanism mediating the rapid impact of
      low-dose BPA in female rat ventricular myocytes. We showed that protein kinase A
      (PKA) and Ca(2+)/CaM-dependent protein kinase II (CAMKII) signaling pathways are
      the two major pathways activated by BPA. Exposure to 1 nM BPA rapidly increased
      production of cAMP and rapidly but transiently increased the phosphorylation of
      the ryanodine receptors by PKA but not by CAMKII. BPA also rapidly increased the
      phosphorylation of phospholamban (PLN), a key regulator protein of sarcoplasmic
      reticulum Ca(2+) reuptake, by CAMKII but not PKA. The increase in CAMKII
      phosphorylation of PLN was mediated by phospholipase C and inositol trisphosphate
      receptor-mediated Ca(2+) release, likely from the endoplasmic reticulum Ca(2+)
      storage. These two pathways are likely localized, impacting only their respective
      target proteins. The rapid impacts of BPA on ryanodine receptors and PLN
      phosphorylation were mediated by estrogen receptor-beta but not estrogen receptor
      alpha. BPA's rapid signaling in cardiac myocytes did not involve activation of
      ERK1/2. Functional analysis showed that PKA but not CAMKII activation contributed
      to BPA-induced sarcoplasmic reticulum Ca(2+) leak, and both PKA and CAMKII were
      necessary contributors to the stimulatory effect of BPA on arrhythmogenesis.
      These results provide mechanistic insight into BPA's rapid proarrhythmic actions
      in female cardiac myocytes and contribute to the assessment of the consequence
      and potential cardiac toxicity of BPA exposure. 

PMID- 24140713
TI  - Hemin therapy improves kidney function in male streptozotocin-induced diabetic
      rats: role of the heme oxygenase/atrial natriuretic peptide/adiponectin axis.
AB  - Diabetic nephropathy is characterized by elevated macrophage infiltration and
      inflammation. Although heme-oxygenase (HO) is cytoprotective, its role in
      macrophage infiltration and nephropathy in type 1 diabetes is not completely
      elucidated. Administering the HO inducer, hemin, to streptozotocin-diabetic rats
      suppressed renal proinflammatory macrophage-M1 phenotype alongside several
      proinflammatory agents, chemokines, and cytokines including macrophage
      inflammatory protein 1alpha (MIP-1alpha), macrophage-chemoattractant protein-1
      (MCP-1), TNF-alpha, IL-1beta, IL-6, nuclear factor-kappaB (NF-kappaB), and
      aldosterone, a stimulator of the inflammatory/oxidative transcription factor, NF
      kappaB. Similarly, hemin therapy attenuated extracellular matrix/profibrotic
      proteins implicated in renal injury including fibronectin, collagen-IV, and TGF
      beta1 and reduced several renal histopathological lesions such as
      glomerulosclerosis, tubular necrosis, tubular vacuolization, and interstitial
      macrophage infiltration. Furthermore, hemin reduced markers of kidney dysfunction
      like proteinuria and albuminuria but increased creatinine clearance, suggesting
      improved kidney function. Correspondingly, hemin significantly enhanced the
      antiinflammatory macrophage-M2 phenotype, IL-10, adiponectin, HO-1, HO activity,
      and atrial natriuretic-peptide (ANP), a substance that abates TNF-alpha, IL-6,
      and IL-1beta, with parallel increase of urinary cGMP, a surrogate marker of ANP.
      Contrarily, coadministering the HO inhibitor, chromium-mesoporphyrin with the HO
      inducer, hemin nullified the antidiabetic and renoprotective effects, whereas
      administering chromium-mesoporphyrin alone abrogated basal HO activity, reduced
      basal adiponectin and ANP levels, aggravated hyperglycemia, and further increased
      MCP-1, MIP-1alpha, aldosterone, NF-kappaB, TNF-alpha, IL-6, IL-1beta,
      proteinuria/albuminuria, and aggravated creatinine clearance, thus exacerbating
      renal dysfunction, suggesting the importance of the basal HO-adiponectin-ANP axis
      in renoprotection and kidney function. Collectively, these data suggest that
      hemin ameliorates diabetic nephropathy by selectively enhancing the
      antiinflammatory macrophage-M2 phenotype and IL-10 while concomitantly abating
      the proinflammatory macrophage-M1 phenotype and suppressing extracellular
      matrix/profibrotic factors with reduction of renal lesions including interstitial
      macrophage infiltration. Because aldosterone stimulate NF-kappaB, which activates
      cytokines like TNF-alpha, IL-6, IL-1beta that in turn stimulate chemokines such
      as MCP-1 and MIP-1alpha to promote macrophage-M1 infiltration, the hemin
      dependent potentiation of the HO-adiponectin-ANP axis may account for reduced
      macrophage infiltration and inflammatory insults in streptozotocin-diabetic rats.

PMID- 24140715
TI  - beta-Arrestin 2 is a mediator of GnRH-(1-5) signaling in immortalized GnRH
      neurons.
AB  - We have previously demonstrated that the cleavage product of the full-length
      GnRH, GnRH-(1-5), is biologically active, binds G protein-coupled receptor 173
      (GPR173), and inhibits the migration of cells in the immortalized GnRH-secreting
      GN11 cell. In this study, we attempted to characterize the GnRH-(1-5)
      intracellular signaling mechanism. To determine whether the signaling pathway
      mediating GnRH-(1-5) regulation of migration involves a G protein-dependent
      mechanism, cells were treated with a generic G protein antagonist in the presence
      and absence of GnRH-(1-5), and a wound-healing assay was conducted to measure
      migration. G Protein antagonist 2 treatment abolished the GnRH-(1-5) inhibition
      of migration, indicating that the mechanism of GnRH-(1-5) is G protein coupled.
      To identify the potential Galpha-subunit recruited by GnRH-(1-5) binding GPR173,
      we measured the second messengers cAMP and inositol triphosphate levels. GnRH-(1
      5) treatment did not alter cAMP levels relative to cells treated with vehicle or
      forskolin, suggesting that GnRH-(1-5) does not couple to the Galphas or Galphai
      subunits. Similarly, inositol triphosphate levels remained unchanged with GnRH-(1
      5) treatment, indicating a mechanism not mediated by the Galphaq/11 subunit.
      Therefore, we also examined whether GnRH-(1-5) activating GPR173 deviated from
      the canonical G protein-coupled receptor signaling pathway by coupling to beta
      arrestin 1/2 to regulate migration. Our coimmunoprecipitation studies indicate
      that GnRH-(1-5) induces the rapid interaction between GPR173 and beta-arrestin 2
      in GN11 cells. Furthermore, we demonstrate that this association recruits
      phosphatase and tensin homolog to mediate the downstream action of GnRH-(1-5).
      These findings suggest that the GnRH-(1-5) mechanism deviates from the canonical
      G protein-coupled receptor pathway to regulate cell migration in immortalized
      GnRH neurons. 

PMID- 24140714
TI  - Calcium regulates FGF-23 expression in bone.
AB  - Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23),
      a bone-derived phosphate and vitamin D-regulating hormone. To better understand
      the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3
      [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and
      in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2(-/-)
      and Cyp27b1(-/-) mutant mice. Gcm2(-/-) mice exhibited low serum PTH and
      1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1(
      /-) mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and
      hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models.
      Doxercalciferol administration increased serum FGF-23 levels in both mutant
      models. PTH administration to Gcm2(-/-) mice also increased serum FGF-23 levels,
      in association with an increase in both 1,25(OH)2D and calcium concentrations.
      Multiple regression analysis of pooled data indicated that changes in FGF-23 were
      positively correlated with serum calcium and 1,25(OH)2D but not related to
      changes in serum phosphate concentrations. A high-calcium diet also increased
      serum FGF-23 concentrations in Cyp27b1(-/-) mice in the absence of 1,25(OH)2D and
      in Gcm2(-/-) mice with low PTH. The addition of calcium to the culture media also
      stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23
      promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel
      inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic
      low calcium to prevent 1,25(OH)2D and PTH stimulation of FGF-23 in these mutant
      mouse models suggest that suppression of FGF-23 plays an important physiological
      adaptive response to hypocalcemia. 

PMID- 24140716
TI  - Thyroid and bone: macrophage-derived TSH-beta splice variant increases murine
      osteoblastogenesis.
AB  - It is now firmly established that TSH may influence the physiology and patho
      physiology of bone by activating osteoblasts and inhibiting osteoclast activity
      resulting in relative osteoprotection. Whether this influence is directly exerted
      by pituitary-derived TSH in vivo is less certain, because we have previously
      reported that the suppression of pituitary TSH does not remove such protection.
      Here, we have characterized the functional relevance of a novel form of the TSH
      beta subunit, designated TSH-betav, known to be produced by murine bone marrow
      cells. We found that fresh bone marrow-derived macrophages (MOs) preferentially
      produced TSH-betav and, when cocultured with CHO cells engineered to overexpress
      the full-length TSH receptor, were able to generate the production of
      intracellular cAMP; a phenomenon not seen in control CHO cells, such results
      confirmed the bioactivity of the TSH variant. Furthermore, cocultures of MOs and
      osteoblasts were shown to enhance osteoblastogenesis, and this phenomenon was
      markedly reduced by antibody to TSH-beta, suggesting direct interaction between
      MOs and osteoblasts as observed under the electron microscope. These data suggest
      a new paradigm of local modulation of bone biology by a MO-derived TSH-like
      molecule and raise the question of the relative contribution of local vs
      pituitary-derived TSH in osteoprotection. 

PMID- 24140718
TI  - Comparative analysis of error-prone replication mononucleotide repeats across
      baculovirus genomes.
AB  - Genome replication by the baculovirus DNA polymerase often generates errors in
      mononucleotide repeat (MNR) sequences due to replication slippage. This results
      in the inactivation of genes that affects different stages of the cell infection
      cycle. Here we mapped these MNRs in the 59 baculovirus genomes. We found that the
      MNR frequencies of baculovirus genomes are different and not correlated with the
      genome sizes. Although the average A/T content of baculoviruses is 58.67%, the
      A/T MNR frequency is significantly higher than that of the G/C MNRs. Furthermore,
      the A7/T7 MNRs are the most frequent of those we studied. Finally, MNR
      frequencies in different classes of baculovirus genes, such as immediate early
      genes, show differences between baculovirus genomes, suggesting that the
      distribution and frequency of different MNRs are unique to each baculovirus
      species or strain. Therefore, the results of this study can help select
      appropriate baculoviruses for the development of biological insecticides. 

PMID- 24140717
TI  - Cross-species withdrawal of MCL1 facilitates postpartum uterine involution in
      both the mouse and baboon.
AB  - A successful postpartum involution permits the postnatal uterus to rapidly regain
      its prepregnancy function and size to ultimately facilitate an ensuing blastocyst
      implantation. This study investigates the molecular mechanisms that govern the
      initiation of the involution process by examining the signaling events that occur
      as the uterus transitions from the pregnant to postnatal state. Using mouse and
      baboon uteri, we found a remarkable cross-species conservation at the signal
      transduction level as the pregnant uterus initiates and progresses through the
      involution process. This study originated with the observation of elevated levels
      of caspase-3 activation in both the laboring mouse and baboon uterus, which we
      found to be apoptotic in nature as evidenced by the concurrent appearance of
      cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and
      potential tocolytic role for uterine caspase-3 during pregnancy regulated by
      increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1
      and X-linked inhibitor of apoptosis. In contrast, this study determined that
      diminished antiapoptotic signaling in the postpartum uterus allowed for both
      endometrial apoptotic and myometrial autophagic episodes, which we speculate are
      responsible for the rapid reduction in size of the postpartum uterus. Using our
      human telomerase immortalized myometrial cell line and the Simian virus-40
      immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of
      antiapoptotic signaling was also an upstream event for both the autophagic and
      apoptotic processes in the human uterine myocyte and endometrial epithelial cell.

PMID- 24140719
TI  - Structural and molecular features of the endomyometrium in endometriosis and
      adenomyosis.
AB  - BACKGROUND Adenomyosis and endometriosis were initially described as
      'adenomyoma'. When the retrograde menstruation theory became widely accepted to
      explain the pathogenesis of endometriosis, since it does not explain adenomyosis,
      the two conditions came to be seen as distinct entities. However, emerging
      evidence suggests that both diseases may be linked to changes in the inner
      portion of the myometrium. In addition, similar anomalies were found in the
      eutopic endometrium of the two conditions and the debate has re-opened. A common
      origin for both adenomyosis and endometriosis would have relevance not only for
      understanding uterine function and pathophysiology, but also for clinical
      management and treatment. METHODS The Scopus and Medline databases were searched
      for all original articles published in English up to the end of 2012. Search
      terms included 'adenomyosis'; 'endometriosis'; 'endometrium'; 'eutopic
      endometrium'; 'inner myometrium'; 'junctional zone'. Special attention was paid
      to articles comparing features of eutopic endometrium in the two conditions.
      RESULTS A number of similarities exist between adenomyosis and endometriosis and,
      by using magnetic resonance and laparoscopy, it was found that, at least in some
      subgroups, the two conditions often coexist. In both situations the inner
      myometrium (or junctional zone) is altered, although alterations are much more
      marked in adenomyosis where a thickness >12 mm is today considered sufficient for
      diagnosis. Research has shown differences between the eutopic endometrium of
      women with both diseases when compared with controls. There is an immune
      dysfunction and there are alterations of adhesion molecules, cell proliferation
      and apoptosis. An increase in cytokines and inflammatory mediators has also been
      observed. Finally, the presence of oxidative stress and anomalies in free-radical
      metabolism may alter uterine receptivity. When the two conditions were compared,
      dissimilarities were also observed in the extent of apoptosis inhibition and in
      the expression of some inflammatory mediators. It is not clear if observed
      differences are primarily related to presenting symptoms. Finally, both
      conditions are steroid dependent and research suggests a role for epigenetic
      mechanisms. The analysis indicates that much of the published research may have
      been influenced by the method of diagnosis and/or has not been controlled for the
      presenting symptoms, the concomitant presence of both diseases or full
      consideration of fluctuations within cycle phase. CONCLUSIONS It is difficult to
      draw firm conclusions from existing evidence since major diagnostic limitations
      still exist and there is a systematic bias in clinical presentation. In addition,
      scanty information is available on the natural history of endometriosis and no
      studies exist on the natural history of adenomyosis. Notwithstanding these
      limitations, a number of similarities, but also some differences have been found
      between the eutopic endometrium in the two diseases. These findings need to be
      taken with considerable caution as the few instances where the research was
      repeated yielded conflicting results. 

PMID- 24140720
TI  - Exosomes as new vesicular lipid transporters involved in cell-cell communication
      and various pathophysiologies.
AB  - Exosomes are nanovesicles that have emerged as a new intercellular communication
      system between an intracellular compartment of a donor cell towards the periphery
      or an internal compartment of a recipient cell. The bioactivity of exosomes
      resides not only in their protein and RNA contents but also in their lipidic
      molecules. Exosomes display original lipids organized in a bilayer membrane and
      along with the lipid carriers such as fatty acid binding proteins that they
      contain, exosomes transport bioactive lipids. Exosomes can vectorize lipids such
      as eicosanoids, fatty acids, and cholesterol, and their lipid composition can be
      modified by in-vitro manipulation. They also contain lipid related enzymes so
      that they can constitute an autonomous unit of production of various bioactive
      lipids. Exosomes can circulate between proximal or distal cells and their fate
      can be regulated in part by lipidic molecules. Compared to their parental cells,
      exosomes are enriched in cholesterol and sphingomyelin and their accumulation in
      cells might modulate recipient cell homeostasis. Exosome release from cells
      appears to be a general biological process. They have been reported in all
      biological fluids from which they can be recovered and can be monitors of
      specific pathophysiological situations. Thus, the lipid content of circulating
      exosomes could be useful biomarkers of lipid related diseases. Since the first
      lipid analysis of exosomes ten years ago detailed knowledge of exosomal lipids
      has accumulated. The role of lipids in exosome fate and bioactivity and how they
      constitute an additional lipid transport system are considered in this review. 

PMID- 24140721
TI  - Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats.
AB  - The aim of the present study was the in vivo evaluation of thiomer-coated
      liposomes for an oral application of peptides. For this purpose, salmon
      calcitonin was chosen as a model drug and encapsulated within liposomes.
      Subsequently, the drug loaded liposomes were coated with either chitosan
      thioglycolic acid (CS-TGA) or an S-protected version of the same polymer (CS-TGA
      MNA), leading to an increase in the particle size of about 500 nm and an increase
      in the zeta potential from approximately -40 mV to a maximum value of about +44
      mV, depending on the polymer. Coated liposomes were demonstrated to effectively
      penetrate the intestinal mucus layer where they came in close contact with the
      underlying epithelium. To investigate the permeation enhancing properties of the
      coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate
      labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes
      coated with CS-TGA-MNA showed the highest effect, leading to a 3.8-fold increase
      in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the
      different formulations was carried out by the oral application of 40 MUg of sCT
      per rat, either encapsulated within uncoated liposomes, CS-TGA-coated liposomes
      or CS-TGA-MNA-coated liposomes, or given as a solution serving as negative
      control. The blood calcium level was monitored over a time period of 24h. The
      highest reduction in the blood calcium level, to a minimum of 65% of the initial
      value after 6h, was achieved for CS-TGA-MNA-coated liposomes. Comparing the areas
      above curves (AAC) of the blood calcium levels, CS-TGA-MNA-coated liposomes led
      to an 8.2-fold increase compared to the free sCT solution if applied orally in
      the same concentration. According to these results, liposomes coated with S
      protected thiomers have demonstrated to be highly valuable carriers for enhancing
      the oral bioavailability of salmon calcitonin.

PMID- 24140723
TI  - Coinciding functions for miR-145 in vascular smooth muscle and cardiac
      fibroblasts.

PMID- 24140722
TI  - Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond.
AB  - The ubiquitin-proteasome system (UPS) is the major intracellular degradation
      system, and its proper function is critical to the health and function of cardiac
      cells. Alterations in cardiac proteasomes have been linked to several
      pathological phenotypes, including cardiomyopathies, ischemia-reperfusion injury,
      heart failure, and hypertrophy. Defects in proteasome-dependent cellular protein
      homeostasis can be causal for the initiation and progression of certain
      cardiovascular diseases. Emerging evidence suggests that the UPS can specifically
      target proteins that govern pathological signaling pathways for degradation, thus
      altering downstream effectors and disease outcomes. Alterations in UPS-substrate
      interactions in disease occur, in part, due to direct modifications of 19S, 11S
      or 20S proteasome subunits. Post-translational modifications (PTMs) are one facet
      of this proteasomal regulation, with over 400 known phosphorylation sites, over
      500 ubiquitination sites and 83 internal lysine acetylation sites, as well as
      multiple sites for caspase cleavage, glycosylation (such as O-GlcNAc
      modification), methylation, nitrosylation, oxidation, and SUMOylation. Changes in
      cardiac proteasome PTMs, which occur in ischemia and cardiomyopathies, are
      associated with changes in proteasome activity and proteasome assembly; however
      several features of this regulation remain to be explored. In this review, we
      focus on how some of the less common PTMs affect proteasome function and alter
      cellular protein homeostasis. This article is part of a Special Issue entitled
      "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy". 

PMID- 24140725
TI  - Achalasia. Conclusions.

PMID- 24140724
TI  - Differential expression of embryonic epicardial progenitor markers and
      localization of cardiac fibrosis in adult ischemic injury and hypertensive heart
      disease.
AB  - During embryonic heart development, the transcription factors Tcf21, Wt1, and
      Tbx18 regulate activation and differentiation of epicardium-derived cells,
      including fibroblast lineages. Expression of these epicardial progenitor factors
      and localization of cardiac fibrosis were examined in mouse models of
      cardiovascular disease and in human diseased hearts. Following ischemic injury in
      mice, epicardial fibrosis is apparent in the thickened layer of subepicardial
      cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant
      expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure
      overload or hypertensive heart disease, but not following ischemic injury. Areas
      of interstitial fibrosis in ischemic and hypertensive hearts actively express
      Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial
      progenitor factors are distinct from CD45-positive immune cells. In human
      diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is
      detected with epicardial, perivascular, and interstitial fibrosis, indicating
      conservation of reactivated developmental mechanisms in cardiac fibrosis in mice
      and humans. Together, these data provide evidence for distinct fibrogenic
      mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different
      fibroblast populations in response to specific types of cardiac injury. 

PMID- 24140726
TI  - Insights into the determination of molecular structure from diffraction data
      using a Bayesian algorithm.
AB  - The determination of the molecular ordering in a liquid is still a controversial
      subject. There is no general consensus either on the methods to obtain reliable
      liquid structures or on the way to analyze them. Regardless of the method, it is
      very important to have a realistic molecular structure available that allows
      simulations to faithfully reproduce the sample features, and that minimizes the
      computing time in structure refinements. However, attention is not always paid to
      this point and molecular models coming from general force-fields are frequently
      used to undertake many of the analyses. We propose in this work to use a Bayesian
      scheme to fit the experimental data and produce reliable molecular models that
      can be used as the starting point of any simulation or refinement. The algorithm
      behind the proposed method is based on a Markov chain Monte Carlo procedure, as
      many other refinement programs such as reverse Monte Carlo or empirical potential
      structure refinement. 

PMID- 24140728
TI  - Graphene nanoribbon-PVA composite as EMI shielding material in the X band.
AB  - A very thin graphene nanoribbon/polyvinyl alcohol (GNR/PVA) composite film has
      been developed which is light weight and requires a very low concentration of
      filler to achieve electromagnetic interference (EMI) shielding as high as 60 dB
      in the X band. Atomic force microscope studies show very well conjugated filler
      concentration in the PVA matrix for varying concentrations of GNR supported by
      Raman spectroscopy data. The films show 14 orders of increase in conductivity
      with a GNR concentration of 0.75% [corrected] in PVA. This is possible because of
      the interconnected GNR network providing a very low percolation threshold as
      observed from the electrical measurements. Local density of states study of GNR
      using scanning tunnelling spectroscopy shows the presence of localized states
      near the Fermi energy. There are multiple advantages of GNR as an EMI shielding
      material in a polymer matrix. It has good dispersion in water, the conductive
      network in the composite shows very high electrical conductivity for a very low
      concentration of GNR and the presence of localized density of states near Fermi
      energy provides the spin states required for the absorbance of radiation energy
      in the X band.

PMID- 24140729
TI  - Prognostic value of peripheral arterial tonometry in patients with coronary
      artery disease and a high cardiovascular risk profile.
AB  - AIM: Data regarding the prognostic value of peripheral endothelial function
      testing in patients with cardiovascular disease are conflicting. Peripheral
      arterial tonometry(PAT) is increasingly used to measure the peripheral
      endothelial function. The prognostic value of this method has not been
      investigated thus far in patients with cardiovascular disease and/or a high
      cardiovascular risk profile. METHODS: In 96 patients with significant coronary
      artery disease(CAD) or<70% stenosis and >= three cardiovascular risk factors,
      reactive hyperemia was induced following upper arm occlusion and the PAT-ratio
      between baseline and hyperemia was calculated. The patients were followed for
      cardiovascular events(revascularization, acute coronary syndrome, ischemic
      stroke, cardiovascular death, repeat coronary angiography due to chest pain) for
      44+/-14 months. The first event was included in the combined end point. RESULTS:
      The study cohort was divided according to the median PAT-ratio(1.91). The
      combined end point occurred in 14 patients with a PAT-ratio below the
      median(1.91) and in 12 patients with a PAT-ratio of >=1.91 (p=0.65). In a
      subgroup of 76 patients, the PAT-ratio was reassessed after six months. No
      differences in the event rate were found between the patients who exhibited
      deterioration(n=50) and those who exhibited an improvement in the PAT-ratio of
      >0.1(n=26; 22 vs. 32%, p=0.32). The combined end point occurred earlier in the
      patients with a PAT-ratio within the 1st tertile than in those with a PAT-ratio
      within the 2nd/3rd tertile(11.3+/-11.0 vs. 27.5+/-18.6 months, p=0.03).
      CONCLUSIONS: In patients with established CAD or a high cardiovascular risk
      profile, the PAT-ratio cannot be used to predict the risk of future
      cardiovascular events. However, a lower PAT-ratio may be associated with the
      earlier occurrence of cardiovascular events.

PMID- 24140727
TI  - Behavioral disturbances in adult mice following neonatal virus infection or
      kynurenine treatment--role of brain kynurenic acid.
AB  - Exposure to infections in early life is considered a risk-factor for developing
      schizophrenia. Recently we reported that a neonatal CNS infection with influenza
      A virus in mice resulted in a transient induction of the brain kynurenine
      pathway, and subsequent behavioral disturbances in immune-deficient adult mice.
      The aim of the present study was to investigate a potential role in this regard
      of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N
      methyl-D-aspartic acid (NMDA) receptor and at the cholinergic alpha7 nicotinic
      receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33
      virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine
      (2*200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse
      inhibition of the acoustic startle, anxiety, and learning and memory were also
      assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine
      induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L
      kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5
      mg/kg i.p.) increase in locomotor activity as well as mild impairments in
      prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine
      release in the striatum in kynurenine-treated mice. These long-lasting behavioral
      and neurochemical alterations suggest that the kynurenine pathway can link early
      life infection with the development of neuropsychiatric disturbances in
      adulthood.

PMID- 24140730
TI  - Relationship between statin type and responsiveness to clopidogrel in patients
      treated with percutaneous coronary intervention: a subgroup analysis of the CILON
      T trial.
AB  - AIM: To compare the responsiveness to clopidogrel in patients who were prescribed
      two different types of statins, atorvastatin vs. rosuvastatin, following
      percutaneous coronary intervention. METHODS: A total of 915 patients were
      randomized according to the antiplatelet therapy strategy in the CILON-T trial.
      In this subgroup analysis, we included patients who took atorvastatin(20 mg/day,
      n=295) or rosuvastatin(10 mg/day, n=261) during the entire study period and
      underwent measurement of the P2Y12 reaction unit(PRU) values at both discharge
      and six months. We compared the P2Y12 reaction unit(PRU) values at six months and
      investigated the relationship between the genotypes of cytochrome P450(CYP) 3A4,
      3A5 and 2C19 with the PRU values at six months in both groups. RESULTS: The
      baseline characteristics did not differ between the groups. There were no
      significant differences in the PRU values at discharge(atorvastatin 221.0+/-87.3
      vs. rosuvastatin 217.1+/-84.7, p=0.59). However, the rosuvastatin group had
      higher PRU values than the atorvastatin group at six months(atorvastatin 226.4+/
      79.3 vs. rosuvastatin 241.5+/-88.2, p=0.033). In the genotype analysis, the
      number of CYP2C19 loss-of-function (LOF) alleles((*)2 or (*)3) was positively
      associated with a higher PRU value in both statin groups, and there were no
      significant interactions regarding the PRU values between the number of CYP 2C19
      LOF alleles and the type of statin(p for interaction=0.56). In the multivariate
      analysis, the use of rosuvastatin was a significant predictor of a PRU value of
      >273(the highest tertile)(OR 1.67, 95% confidence interval 1.05-2.65, p=0.031).
      CONCLUSIONS: Rosuvastatin is associated with high on-treatment platelet
      reactivity compared with atorvastatin following the coadministration of
      clopidogrel for six months. Further studies are therefore warranted to clarify
      the mechanism underlying this relationship.

PMID- 24140731
TI  - Fine tuning and measurement of mechanical properties of crosslinked hyaluronic
      acid hydrogels as biomimetic scaffold coating in regenerative medicine.
AB  - Chemically crosslinked hyaluronic acid hydrogels are synthesized with a
      homogeneous crosslinking process using divinyl sulfone (DVS) as crosslinking
      agent. Testing different conditions, in terms of both DVS content and curing
      time, we aim to keep control over the crosslinking process in order to prepare
      biocompatible hydrogels with mechanical properties closely approximating those of
      extracellular matrix (ECM) of natural stem cells niches (0.1/50kPa). The
      hydrogels properties are evaluated through a reliable methodology based on three
      independent techniques: dynamic rheological analysis, used as benchmark method;
      swelling experiments following the Flory-Rehner theory and atomic force
      microscope (AFM) nanoindentation experiments. Our results demonstrate that
      controlling crosslinking parameters it is possible to design hydrogels with
      desired elastic moduli values. HA hydrogels can be ideal coating materials to be
      implemented in regenerative medicine and particularly in the engineering of ECM
      niches in vitro. 

PMID- 24140732
TI  - Enhancing glass ionomer cement features by using the HA/YSZ nanocomposite: a feed
      forward neural network modelling.
AB  - Despite brilliant properties of glass ionomer cement (GIC), its weak mechanical
      property poses an obstacle for its use in medical applications. The present
      research aims to formulate hydroxyapatite/yttria-stabilized zirconia (HA/YSZ) in
      the composition of GIC to enhance mechanical properties and to improve fluoride
      release of GIC. HA/YSZ was synthesized via a sol-gel method and characterized by
      applying X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT
      IR), X-ray photo-emission spectroscopy (XPS) and simultaneous thermal analysis
      (STA) along with transmission electron microscopy (TEM) methods. The synthesized
      nanocomposite was mixed with GIC at a fixed composition of 5wt%. The effect of
      different weight percentages of YSZ:HA on GIC was investigated by measuring the
      compressive strength, diametral tensile strength, microhardness and fluoride
      release. The results showed that, after 1 and 7 days of setting, the 20wt%
      nanohydroxyapatite/80wt% stabilized zirconia cement exhibited higher compressive
      strength (1857-245MPa), higher diametral tensile strength (11-14MPa) and greater
      microhardness (104-106MPa) as compared with the pure GIC (65-88MPa in compressive
      strength, 5-9.5MPa in diametral tensile strength and 70-89MPa in microhardness).
      The reinforced cement, also, exhibited higher fluoride release compared with pure
      GIC. The artificial neural network (ANN) was trained for modeling the system.
      Results obtained by ANN have proved to be completely in accordance with
      expectations. 

PMID- 24140739
TI  - Understanding linear regression.

PMID- 24140738
TI  - Instrumental activities of daily living staging as a possible clinical tool for
      falls risk assessment in physical medicine and rehabilitation.
AB  - OBJECTIVE: To determine whether instrumental activity of daily living (IADL)
      limitation stages can distinguish among elderly, community-dwelling persons with
      high likelihoods to have fallen once and more than once. DESIGN: A cross
      sectional survey. SETTING: A nationally representative sample from the Second
      Longitudinal Study of Aging (LSOA II). PARTICIPANTS: Included were 7401 community
      dwelling persons 70 years of age and older. METHODS: The association of falling
      once and more than once within the past 12 months and 5 stages of increasing IADL
      limitation were explored by using a multinomial logistic regression model that
      controlled for demographics, education, perceived lack of home accessibility
      features, and health conditions. Sample proportions were weighted to reflect the
      prevalence in the U.S. population of 1994. MAIN OUTCOME MEASUREMENTS: Subject
      recall of fall history. There were 3 categories for this variable: no fall,
      falling once, and falling more than once in the past 12 months. RESULTS: Compared
      with IADL stage 0, the adjusted relative risk ratio of falling once peaked in
      individuals at IADL stage II at 2.0 (95% confidence interval [CI], 1.5-2.6), and
      those at IADL stage III had a relative risk ratio of 1.8 (95% CI, 1.3-2.6). The
      relative risk ratio of falling more than once was 2.1 (95% CI, 1.7-2.6), 4.0 (95%
      CI, 3.0-5.3), 3.7 (95% CI, 2.8-5.0), and 2.7 (95% CI, 1.5-4.9) for IADL stages I,
      II, III, and IV, respectively, when treating IADL stage 0 as reference.
      CONCLUSIONS: IADL limitation stages could represent a powerful and practical tool
      for screening patients in the U.S. elderly population according to fall risk.
      Clinical implementation and prospective testing for validation as a screening
      tool would be necessary.

PMID- 24140737
TI  - Identification of distinct monocyte phenotypes and correlation with circulating
      cytokine profiles in acute response to spinal cord injury: a pilot study.
AB  - BACKGROUND: Macrophage infiltration to the injury site during the acute response
      to traumatic spinal cord injury (SCI) is not uniform. Macrophage phenotype has
      been characterized as either proinflammatory (M1) or anti-inflammatory (M2).
      Results of animal studies suggest that M1 or M2 dominance at the site of injury
      relates to spontaneous recovery after SCI. OBJECTIVE: To investigate whether the
      phenotype of circulating macrophage precursors-monocytes (MO) is altered in the
      acute phase of SCI and corresponds to circulating inflammatory cytokines. STUDY
      DESIGN: A prospective observational cohort study. SETTING: A single academic
      medical center in Pennsylvania. PATIENTS: A cohort of 27 subjects with complete
      or incomplete traumatic SCI enrolled within 7 days after SCI injury. METHODS: The
      MO phenotype was defined within the first week after SCI by using flow cytometry
      and was compared with that of historic uninjured controls. Concentrations of 25
      cytokines and/or chemokines were assessed by using Luminex in serial blood
      samples up to 2 weeks after SCI. An analysis of variance was used to determine
      the correlations between the phenotypes and the cytokine profiles. RESULTS:
      Patient subsets were identified with either M1- or M2-dominant circulating MOs
      distinct from the uninjured controls. The M1 dominant was associated with higher
      circulating levels of proinflammatory mediators interleukin (IL)12p70 and
      interferon gamma-induced protein 10 kDa (IP-10/CXCL10), and lower levels of anti
      inflammatory cytokines IL-10, IL-15, and IL-7, whereas the M2 dominant exhibited
      the opposite cytokine profiles with significantly higher IL-10 and IL-7.
      CONCLUSION: In the acute phase after SCI, at comparable injury severity,
      subgroups of patients exhibit distinct M1 or M2 MOs dominance and the phenotype
      is correlated with M1- or M2-specific cytokine and/or chemokine profiles.
      Although further studies are needed to determine how these observed phenotypic
      differences relate to functional recovery, our findings (1) provide the first
      evidence, to our knowledge, that indicates the possible individual differences in
      the immune responses to the comparable traumatic SCI, with potential implications
      for management of acute SCI and rehabilitation; and (2) may represent easily
      accessible biomarkers with prognostic utility.

PMID- 24140740
TI  - Brain-computer interface based on intermodulation frequency.
AB  - OBJECTIVE: Most recent steady-state visual evoked potential (SSVEP)-based brain
      computer interface (BCI) systems have used a single frequency for each target, so
      that a large number of targets require a large number of stimulus frequencies and
      therefore a wider frequency band. However, human beings show good SSVEP responses
      only in a limited range of frequencies. Furthermore, this issue is especially
      problematic if the SSVEP-based BCI takes a PC monitor as a stimulator, which is
      only capable of generating a limited range of frequencies. To mitigate this
      issue, this study presents an innovative coding method for SSVEP-based BCI by
      means of intermodulation frequencies. APPROACH: Simultaneous modulations of
      stimulus luminance and color at different frequencies were utilized to induce
      intermodulation frequencies. Luminance flickered at relatively large frequency
      (10, 12, 15 Hz), while color alternated at low frequency (0.5, 1 Hz). An
      attractive feature of the proposed method was that it would substantially
      increase the number of targets at a single flickering frequency by altering color
      modulated frequencies. Based on this method, the BCI system presented in this
      study realized eight targets merely using three flickering frequencies. MAIN
      RESULTS: The online results obtained from 15 subjects (14 healthy and 1 with
      stroke) revealed that an average classification accuracy of 93.83% and
      information transfer rate (ITR) of 33.80 bit min(-1) were achieved using our
      proposed SSVEP-based BCI system. Specifically, 5 out of the 15 subjects exhibited
      an ITR of 40.00 bit min(-1) with a classification accuracy of 100%. SIGNIFICANCE:
      These results suggested that intermodulation frequencies could be adopted as
      steady responses in BCI, for which our system could be used as a practical BCI
      system.

PMID- 24140741
TI  - Silver-doped manganese dioxide and trioxide nanoparticles inhibit both gram
      positive and gram negative pathogenic bacteria.
AB  - Palladium, ruthenium and silver-doped MnO2 and silver doped Mn2O3 nanoparticles
      were synthesized by simple co-precipitation technique. SEM-TEM analysis revealed
      the nano-size of these synthesized samples. XPS data illustrates that Mn is
      present in 4+ and 3+ oxidation states in MnO2 and Mn2O3 respectively. Thermal
      analysis gave significant evidence for the phase changes with increasing
      temperature. Antibacterial activity of these synthesized nanoparticles on three
      Gram positive bacterial cultures (Staphylococcus aureus ATCC 6538, Streptococcus
      epidermis ATCC 12228, Bacillus subtilis ATCC 6633) and three Gram negative
      cultures (Escherichia coli ATCC 8739, Salmonella abony NCTC 6017 and Klebsiella
      pneumoniae ATCC 1003) was investigated using a disc diffusion method and
      live/dead assay. Only Ag-doped MnO2 and Ag-doped Mn2O3 nanoparticles showed
      antibacterial property against all six-test bacteria but Ag-doped MnO2 was found
      to be more effective than Ag-doped Mn2O3. 

PMID- 24140742
TI  - Interactions of fish gelatin and chitosan in uncrosslinked and crosslinked with
      EDC films: FT-IR study.
AB  - Films based on fish gelatin, chitosan and blend of fish gelatin and chitosan
      before and after cross-linking with EDC have been characterized by FT-IR
      spectroscopy. The FT-IR spectrum of fish gelatin film showed the characteristic
      amide I, amide II and amide III bands, and the FT-IR spectrum of chitosan film
      confirmed that the polymer was only a partially deacetylated product, and
      included CH3-C=O and NH2 groups, the latter both in their free -NH2 and
      protonated -NH3(+) form. Analysis of FT-IR spectra of two-component, fish gelatin
      chitosan film revealed the formation not only of hydrogen bonds within and
      between chains of polymers, but also of electrostatic interactions between -COO(
      ) of gelatin and -NH3(+) of chitosan. Modification with EDC provided cross
      linking of composites of the film. New iso-peptide bonds formed between activated
      carboxylic acid groups of glutamic or aspartic acid residue of gelatin and amine
      groups of gelatin or/and chitosan.

PMID- 24140743
TI  - Synthesis, crystal structure and luminescence properties of the Ln(III)-picrate
      complexes with 1-ethyl-3-methylimidazolium as countercations.
AB  - New anionic complexes of lanthanide picrates containing 1-ethyl-3
      methylimidazolium (EMIm) as countercation have been prepared. The Ln(III)
      complexes were characterized by complexometric titration, elemental analyses,
      infrared spectroscopy and molar conductivity. The molecular structures of the
      (EMIm)2[Ln(Pic)4(H2O)2]Pic complexes, Ln(III)=Sm, Eu, Gd and Tb, and Pic=picrate,
      were determined by X-ray crystallography. In these structures the picrate anion
      appears in three forms: as uncoordinated counteranion, as monodentated and
      bidentate ligand. The coordination polyhedron around the Ln(III) atom can be
      described as tricapped trigonal prismatic molecular geometry. The theoretical
      molecular structures of the complexes were also calculated using the Sparkle/PM3
      model for Ln(III) complexes, allowing analysis of intramolecular energy transfer
      processes of the Eu(III) compound. The spectroscopic properties of the 4f(6)
      intraconfigurational transitions of the Eu(III) complex were then studied
      experimentally and theoretically. The low value of emission quantum efficiency of
      (5)D0 emitting level (eta) of Eu(III) ion (ca. 10%) is due to the vibrational
      modes of the water molecule that act as luminescence quenching. In addition, the
      luminescence decay curves, the experimental intensity parameters (Omegalambda),
      lifetimes (tau), radiative (Arad) and non-radiative (Anrad) decay rates,
      theoretical quantum yield (q) were also determined and discussed. 

PMID- 24140744
TI  - Identification of mixed bromidochloridotellurate anions in disordered crystal
      structures of (bdmim)2[TeX2Y4] (X, Y=Br, Cl; bdmim=1-butyl-2,3
      dimethylimidazolium) by combined application of Raman spectroscopy and solid
      state DFT calculations.
AB  - The discrete mixed [TeBrxCl6-x](2-) anions in their disordered crystal structures
      have been identified by using the phases prepared by the reaction of 1-butyl-2,3
      dimethylimidazolium halogenides (bdmim)X with tellurium tetrahalogenides TeX4
      (X=Cl, Br) as examples. Homoleptic (bdmim)2[TeX6] [X=Cl (1), Br (2)] and mixed
      (bdmim)2[TeBr2Cl4] (3), and (bdmim)2[TeBr4Cl2] (4) are formed depending on the
      choice of the reagents, and their crystal structures have been determined by
      single-crystal X-ray diffraction. The coordination environments of tellurium in
      all hexahalogenidotellurates are almost octahedral. Because of the
      crystallographic disorder, the mixed [TeBr2Cl4](2-) and [TeBr4Cl2](2-) anions in
      3 and 4 cannot be identified in their crystal structures. Pawley refinement of
      the X-ray powder diffraction patterns of 1-4 indicates the presence of single
      phases in all four products. The solid state Raman spectra of 1-4 were assigned
      with help of DFT calculations that were performed both for the discrete anions in
      vacuum and for the complete crystal structures employing periodic boundary
      conditions. The fundamental vibrations of the homoleptic [TeX6](2-) (X=Cl, Br)
      anions could be well reproduced by the solid-state DFT computations and enabled a
      complete assignment of the Raman spectra. While the presence of cis-isomers in
      both [TeBr2Cl4](2-) and [TeBr4Cl2](2-) could be inferred by the computed
      fundamental vibrations, that of trans-isomers among the reaction products is,
      however, also possible. The pathway of the formation of [TeX4Y2](2-) isomers from
      TeX4 and Y(-) (X, Y=Cl, Br) was also explored by DFT calculations both in vacuum
      and in solution and indicated that both reactions afforded 80 mol% of cis-isomers
      and 20 mol% of trans-isomers.

PMID- 24140745
TI  - Chronic elevation of phosphocholine containing lipids in mice exposed to Gulf War
      agents pyridostigmine bromide and permethrin.
AB  - For two decades, 25% of the veterans who served in the 1991 Gulf War (GW) have
      been living with Gulf War Illness (GWI), a chronic multisymptom illness. Evidence
      suggests that brain structures involved in cognitive function may be affected in
      GWI. Gulf War agents such as the acetylcholinesterase (AChE) inhibitor
      pyridostigmine bromide (PB) and the pesticide permethrin (PER) are considered key
      etiogenic factors in GWI. We therefore developed a mouse model of GW agent
      exposure by co-administering PB and PER and showed that this model exhibits
      cognitive impairment and anxiety, and increased astrogliosis at chronic post
      exposure time-points. Since GW agents inhibit AChE, we hypothesized that PB+PER
      exposure will modulate phosphatidylcholine (PC) and sphingomyelin (SM), which are
      reservoirs of phosphocholine required for endogenous ACh synthesis. Lipidomic
      analyses showed that PC and SM were elevated in the brains of exposed compared to
      control mice. Brain ether PC (ePC) species were increased but lyso-platelet
      activating factors (lyso-PAF) that are products of ePC were decreased in exposed
      animals compared to controls. Catalase expression (a marker for peroxisomes) was
      increased in GW agent exposed mice compared to controls. Ether PC and lyso-PAF
      modulation was also evident in the plasma of GW agent exposed mice compared to
      controls. These studies suggest peroxisomal and lysosomal dysfunction in the
      brain at a chronic post-exposure timepoint following GW agent exposure. Our
      studies provide a new direction for GWI research, which will be useful for
      developing suitable therapies for treating GWI. 

PMID- 24140746
TI  - Doxycycline-regulated GDNF expression promotes axonal regeneration and functional
      recovery in transected peripheral nerve.
AB  - Increased production of neurotrophic factors (NTFs) is one of the key responses
      seen following peripheral nerve injury, making them an attractive choice for pro
      regenerative gene therapies. However, the downside of over-expression of certain
      NTFs, including glial cell line-derived neurotrophic factor (GDNF), was earlier
      found to be the trapping and misdirection of regenerating axons, the so-called
      'candy-store' effect. We report a proof-of-principle study on the application of
      conditional GDNF expression system in injured peripheral nerve. We engineered
      Schwann cells (SCs) using dendrimers or lentiviral transduction with the vector
      providing doxycycline-regulated GDNF expression. Injection of GDNF-modified cells
      into the injured peripheral nerve followed by time-restricted administration of
      doxycycline demonstrated that GDNF expression in SCs can also be controlled
      locally in the peripheral nerves of the experimental animals. Cell-based GDNF
      therapy was shown to increase the extent of axonal regeneration, while controlled
      deactivation of GDNF effectively prevented trapping of regenerating axons in GDNF
      enriched areas, and was associated with improved functional recovery. 

PMID- 24140747
TI  - Development of a poly(ether urethane) system for the controlled release of two
      novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent
      bacterial biofilm formation.
AB  - Traditional antibiotic therapy to control medical device-based infections
      typically fails to clear biofilm infections and may even promote the evolution of
      antibiotic resistant species. We report here the development of two novel
      antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX
      (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating
      suspended bacterial growth and biofilm formation. These chelated gallium or zinc
      complexes act as iron siderophore analogs, supplanting the natural iron uptake of
      most bacteria. Poly (ether urethane) (PEU; Biospan(r)) polymer films were
      fabricated for the controlled sustained release of the Ga- or Zn-complexes, using
      an incorporated pore-forming agent, poly(ethylene glycol) (PEG). An optimum
      formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained
      drug release for at least 3months. All drug-loaded PEU films exhibited in vitro
      >= 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative
      (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus
      the negative control PEU films releasing nothing. Cytotoxicity and endotoxin
      evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing
      PEU films. Finally, in vivo studies further substantiate the anti-biofilm
      efficacy of the PEU films releasing Ga- or Zn- complexes.

PMID- 24140748
TI  - Multifunctional nanoparticles for targeted delivery of immune activating and
      cancer therapeutic agents.
AB  - Nanoparticles (NPs) have been extensively investigated for applications in both
      experimental and clinical settings to improve delivery efficiency of therapeutic
      and diagnostic agents. Most recently, novel multifunctional nanoparticles have
      attracted much attention because of their ability to carry diverse
      functionalities to achieve effective synergistic therapeutic treatments.
      Multifunctional NPs have been designed to co-deliver multiple components, target
      the delivery of drugs by surface functionalization, and realize therapy and
      diagnosis simultaneously. In this review, various materials of diverse
      chemistries for fabricating multifunctional NPs with distinctive architectures
      are discussed and compared. Recent progress involving multifunctional NPs for
      immune activation, anticancer drug delivery, and synergistic theranostics is the
      focus of this review. Overall, this comprehensive review demonstrates that
      multifunctional NPs have distinctive properties that make them highly suitable
      for targeted therapeutic delivery in these areas. 

PMID- 24140749
TI  - Determination of key structure-activity relationships in siRNA delivery with a
      mixed micelle system.
AB  - Short interfering ribonucleic acids (siRNAs) offer a highly specific and
      selective form of therapy for diseases with a genetic component; however the poor
      pharmacokinetic properties of the molecule have impeded its development into a
      therapeutic for use in vivo. Several different approaches have been taken to
      develop a successful siRNA delivery system but these systems lack the flexibility
      for easy optimisation. Here, we propose a polymeric nanoparticle (PNP) system
      consisting of two amphiphilic diblock copolymers which allow for the rapid
      determination of structure-activity relationships involving gene knockdown and
      toxicity. The diblock copolymers self-assemble into monodisperse micelles of
      defined hydrodynamic diameters ranging from 30 to 100 nm dependent on the
      copolymer ratio. A luciferase-based high throughput assay varying PNP
      composition, concentration and siRNA concentration allowed the rapid
      identification of efficient PNP formulations for adherent and suspension cell
      lines. Optimised PNPs efficiently knocked down a fusion oncogene in hard to
      transfect human leukaemic cells raising the possibility of targeting malignant
      cells in a cancer-specific fashion. This approach allows the optimum PNP
      formulation to be identified for different cell types and conditions.

PMID- 24140752
TI  - Monte Carlo investigation into feasibility and dosimetry of flat flattening
      filter free beams.
AB  - Flattening filter free (FFF) beams due to their non-uniformity, are sub-optimal
      for larger field sizes. The purpose of this study was to investigate the incident
      electron beam distributions that would produce flat FFF (F4) beams without the
      use of a flattening filter (FF). Monte Carlo (MC) simulations with BEAMnrc and
      DOSXYZnrc codes have been performed to evaluate feasibility of this approach. The
      dose distributions in water for open 6 MV beams were simulated using the Varian
      21EX linac head model, which will be called the FF model. The FF was then removed
      from the FF model, and MC simulations were performed using (1) 6 MeV electrons
      incident on the target and (2) a 6 MeV electron beam with electron angular
      distributions optimized to provide as flat dose profiles as possible.
      Configuration (1) represents FFF beam while configuration (2) allowed producing a
      F4 beam. Optimizations have also been performed to produce flattest profiles for
      a set of dose rates (DRs) in the range from 1.25 to 2.4 of the DR of FF beam.
      Profiles and percentage depth doses (PDDs) from 6 MV F4 beams have been
      calculated and compared to those from the FF beam. Calculated profiles
      demonstrated improved flatness of the FFF beams. In fact, up to field sizes
      within the circle of 35 cm diameter the flatness of F4 beam at dmax was better or
      comparable to that of FF beam. At 20 cm off-axis the dose increased from 52% for
      FFF to 92% for F4 beam. Also, profiles of F4 beams did not change considerably
      with depth. PDDs from F4 beams were similar to those of the FFF beam. The DR for
      the largest modeled (44 cm diameter) F4 beam was higher than the DR from FF beam
      by a factor of 1.25. It was shown that the DR can be increased while maintaining
      beam flatness, but at the cost of reduced field size. 

PMID- 24140751
TI  - Quantification of secretory leukocyte protease inhibitor (SLPI) in oral gargle
      specimens collected using mouthwash.
AB  - BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is an innate immunity
      associated protein known to inhibit HIV transmission, and is thought to inhibit a
      variety of infectious agents, including human papillomaviruses (HPVs). We aimed
      to optimize an established ELISA-based SLPI quantification assay for use with
      oral gargle specimens collected using mouthwash, and to assess preliminary
      associations with age, smoking status, and alcohol intake. METHODS: Oral gargle
      supernatants from 50 individuals were used to optimize the Human SLPI Quantikine
      ELISA Kit. Sample suitability was assessed and quality control analyses were
      conducted. RESULTS: Salivary SLPI was successfully recovered from oral gargles
      with low intra-assay and high inter-individual variability. Initial measurements
      showed that salivary SLPI varied considerably across individuals, and that SLPI
      was inversely associated with age. CONCLUSIONS: This optimized assay can be used
      to examine the role of SLPI in the acquisition of oral HPV and other infections.

PMID- 24140750
TI  - Binding of MgtR, a Salmonella transmembrane regulatory peptide, to MgtC, a
      Mycobacterium tuberculosis virulence factor: a structural study.
AB  - MgtR, a highly hydrophobic peptide expressed in Salmonella enterica serovar
      Typhimurium, inhibits growth in macrophages through binding to the membrane
      protein MgtC that has been identified as essential for replication in
      macrophages. While the Mycobacterium tuberculosis MgtC is highly homologous to
      its S. Typhi analogue, there does not appear to be an Mtb homologue for MgtR,
      raising significant pharmacological interest in this system. Here, solid-state
      NMR and EPR spectroscopy in lipid bilayer preparations were used to demonstrate
      the formation of a heterodimer between S. Typhi MgtR and the transmembrane helix
      4 of Mtb MgtC. Based on the experimental restraints, a structural model of this
      heterodimer was developed using computational techniques. The result is that MgtR
      appears to be ideally situated in the membrane to influence the functionality of
      MgtC. 

PMID- 24140753
TI  - Subchronic exposure to lead acetate inhibits spermatogenesis and downregulates
      the expression of Ddx3y in testis of mice.
AB  - Male mice were given drinking water alone or containing 0.5, 1.0 and 1.5g/L Pb
      acetate for 60 days. After the treatment, the concentrations of Pb were
      determined in the serum and testis of mice by ICP-MS. The gene transcription of
      Usp9y, Ddx3y and Uty and their protein levels in the testis were examined by real
      time PCR, Western blotting and immunohistochemistry. The sperm quality,
      spermatogenesis, and histological alteration of the testis and epididymis were
      observed by microscope. The probability of impregnating female mice by lead
      exposed male was evaluated. It was shown that the concentrations of Pb in serum
      and testis of mice significantly increased in the groups exposed to Pb in a dose
      dependent manner. The male fertility significantly decreased in the groups
      exposed to 1.0 and 1.5g/L Pb acetate. Moreover, exposure to Pb also inhibited
      spermatogenesis and sperm development, and significantly downregulated
      expressions of Ddx3y gene expression in testis of mice, but Usp9y and Uty
      expressions unaffected. 

PMID- 24140754
TI  - Genomic and proteomic analyses of 1,3-dinitrobenzene-induced testicular toxicity
      in Sprague-Dawley rats.
AB  - 1,3-Dinitrobenzene (DNB) is an industrial intermediate and testicular toxicant
      that has been shown to target Sertoli cells. The mechanism of action of DNB in
      the testis, however, is unclear. To investigate global alterations in gene or
      protein expression during testicular toxicity, testes from rats treated orally
      with DNB were subjected to microarray and two-dimensional gel electrophoresis (2
      DE) analyses. Histopathological abnormalities were detected in the testes of the
      DNB-treated rats. Microarray analysis revealed that, during early testicular
      toxicity, several genes involved in apoptosis, germ cell/Sertoli cell junction,
      and tight junction signaling pathways were differentially expressed. Based on 2
      DE analysis, 36 protein spots showing significantly different expression during
      early testicular toxicity were selected and identified. Network analysis of the
      identified proteins revealed that these proteins are associated with cellular
      development or reproductive system diseases. Collectively, these data will help
      clarify the molecular mechanism underlying testicular toxicity in DNB-exposed
      rats. 

PMID- 24140755
TI  - Clopidogrel "resistance": pre- vs post-receptor determinants.
AB  - The clinical efficacy of the P2Y12 receptor antagonist clopidogrel as an agent to
      prevent thrombotic events predominantly reflects its anti-aggregatory effects.
      Stent thrombosis in particular is more likely to occur in patients in whom
      clopidogrel effect is limited. "Resistance" to clopidogrel in general should
      theoretically arise either because of a reduction in plasma concentration of the
      active metabolite and/or of the downstream intracellular biochemical changes
      underlying antiplatelet effects. We therefore postulate that "resistance" to
      clopidogrel arises via a combination of pharmacogenetic, pharmacokinetic and
      intracellular biochemical mechanisms. Considerable attention has been so far
      directed to the finding that stent thrombosis occurs more frequently in patients
      with loss-of-function mutations of CYP2C19, thus limiting clopidogrel
      bioactivation. Furthermore, a number of drug-drug interactions may marginally
      impair responsiveness to clopidogrel, largely via impairment of bioactivation.
      However, population data also suggest that clopidogrel "resistance" occurs more
      frequently in patients with acute coronary syndromes than in normal subjects, and
      that "resistance" is particularly common in obese subjects and with diabetes.
      Here we critically review available literature and speculate on the possibility
      that non-genetic causes of clopidogrel "resistance" may arise from impairments of
      the intracellular signaling cascade initiated by P2Y12 receptor inhibition. In
      such cases, "resistance" to clopidogrel may also theoretically occur with other
      P2Y12 receptor antagonists, irrespective of the need for bioactivation.
      Delineation of this non-genetic component of "resistance" to P2Y12 inhibitors may
      facilitate the development of optimal therapeutic strategies for high-risk
      cardiovascular patients. 

PMID- 24140756
TI  - Thyroid microcarcinoma approach: a ten year experience.
AB  - AIM: To optimize thyroid microcarcinoma approach, through a retrospective
      examination of Authors' experience and literature review. MATERIALS:
      Characteristics, treatment and outcomes of patients affected with thyroid
      microcarcinoma were examined: among 1733 patients operated on for thyroid
      diseases at Endocrine Surgery Unit of San Paolo Hospital in Milan, from 2001 to
      2011, 104 (6.0%) resulted affected with microcarcinoma. Twenty (19.2%) had pre
      operative and 84 (80.8%) post-operative diagnosis, 11 with (N+) and 93 without
      (N0) lymph node metastasis. Eighty-five patients underwent total thyroidectomy,
      11 (N+) total thyroidectomy with lymphoadenectomy and 8 lobectomy, 2 radicalized
      in thyroidectomy. All patients underwent Levo-thyroxine suppressive therapy, 25
      (24.0%) 131I ablation. Differences between N0 and N+ patients were researched.
      RESULTS: Neither recurrences nor death at a mean follow-up of 5.6 years. Tumour
      was multifocal and in thyroid with no other diseases in N+, in a greater rate
      than in N0 patients. DISCUSSION: Microcarcinoma generally has an indolent course,
      but sometimes it presents with nodal metastasis. For this reason its treatment in
      literature is still largely debated. CONCLUSION: In cases of pre-operative
      diagnosis of microcarcinoma without lymph node metastasis, we propose total
      thyroidectomy; otherwise, total thyroidectomy with lymphoadenectomy. In cases of
      post-operative diagnosis, after a partial resection, only selected cases on the
      basis of patients' and tumour features require a completion total thyroidectomy.
      We propose Levo-thyroxine suppressive therapy to all patients, 131I ablation in
      cases of lymphatic metastasis and only in selected cases without metastasis, on
      the basis of patients' and tumour aspects (age, sex, histological variant,
      multifocality).

PMID- 24140758
TI  - Problems caused by heterogeneity in meta-analysis: a case study of acupuncture
      trials.
AB  - OBJECTIVES: To illustrate the pitfalls of using meta-analysis to combine
      estimates of effect in trials that are highly varied and have a high potential
      for bias. METHODS: We used a random-effects meta-analysis to pool the results of
      51 sham-controlled acupuncture trials of chronic pain published in English before
      2008 and explored the heterogeneity using meta-regression. We repeated the
      process on a subset of these trials that used a visually credible non-penetrating
      sham device as control (N = 12). RESULTS: In both analyses there were high levels
      of heterogeneity and many studies were at risk from potential bias. The
      heterogeneity was not explained by meta-regression. CONCLUSIONS: Trials of
      interventions that have high potential for bias, such as many in the acupuncture
      literature, do not meet the assumptions of the statistical procedure that
      underlie random-effects meta-analysis. Even in the absence of bias, heterogeneity
      in meta-analyses is not accounted for by the CIs around the pooled estimate.

PMID- 24140757
TI  - Decisive data sets in phylogenomics: lessons from studies on the phylogenetic
      relationships of primarily wingless insects.
AB  - Phylogenetic relationships of the primarily wingless insects are still considered
      unresolved. Even the most comprehensive phylogenomic studies that addressed this
      question did not yield congruent results. To get a grip on these problems, we
      here analyzed the sources of incongruence in these phylogenomic studies by using
      an extended transcriptome data set. Our analyses showed that unevenly distributed
      missing data can be severely misleading by inflating node support despite the
      absence of phylogenetic signal. In consequence, only decisive data sets should be
      used which exclusively comprise data blocks containing all taxa whose
      relationships are addressed. Additionally, we used Four-cluster Likelihood
      Mapping (FcLM) to measure the degree of congruence among genes of a data set, as
      a measure of support alternative to bootstrap. FcLM showed incongruent signal
      among genes, which in our case is correlated neither with functional class
      assignment of these genes nor with model misspecification due to unpartitioned
      analyses. The herein analyzed data set is the currently largest data set covering
      primarily wingless insects, but failed to elucidate their interordinal
      phylogenetic relationships. Although this is unsatisfying from a phylogenetic
      perspective, we try to show that the analyses of structure and signal within
      phylogenomic data can protect us from biased phylogenetic inferences due to
      analytical artifacts. 

PMID- 24140759
TI  - Therapeutic effect of electroacupuncture in a p75 knockout mouse model of
      progressive hearing loss.

PMID- 24140760
TI  - Excise tax avoidance: the case of state cigarette taxes.
AB  - We conduct an applied welfare economics analysis of cigarette tax avoidance. We
      develop an extension of the standard formula for the optimal Pigouvian corrective
      tax to incorporate the possibility that consumers avoid the tax by making
      purchases in nearby lower tax jurisdictions. To provide a key parameter for our
      formula, we estimate a structural endogenous switching regression model of border
      crossing and cigarette prices. In illustrative calculations, we find that for
      many states, after taking into account tax avoidance the optimal tax is at least
      20% smaller than the standard Pigouvian tax that simply internalizes external
      costs. Our empirical estimate that tax avoidance strongly responds to the price
      differential is the main reason for this result. We also use our results to
      examine the benefits of replacing avoidable state excise taxes with a harder-to
      avoid federal excise tax on cigarettes. 

PMID- 24140761
TI  - Treatment of rheumatoid arthritis with etanercept with reference to disease
      modifying anti-rheumatic drugs: long-term safety and survival using prospective,
      observational data.
AB  - OBJECTIVE: The objective of this study was to examine the long-term safety of
      etanercept (ETN) in comparison with conventional DMARDs in a large observational
      cohort of RA patients in the UK. METHODS: Data were made available from the
      British Society of Rheumatology Biologics Register for a cohort of patients with
      RA treated with ETN and a reference cohort of RA patients treated with
      conventional DMARDs (maximum follow-up 10 years). The adjusted risk of events was
      compared using Cox proportional hazards models. RESULTS: There were 3529 eligible
      ETN-treated patients (16,919 person-years) and 2864 conventional DMARD-treated
      patients (11,095 person-years), with notable differences between groups at
      baseline. Crude mortality rates were 12.0 vs 20.1 events per 1000 person-years
      for ETN and conventional DMARD patients, respectively, with an adjusted hazard
      ratio (aHR) of 0.72 (95% CI 0.54, 0.96). There was no difference in the long-term
      risk of serious infections (aHR = 1.02, 95% CI 0.83, 1.25). However, the risk was
      increased for ETN in the first 2 years (aHR = 1.56, 95% CI 1.16, 2.09; aHR =
      1.32, 95% CI 1.06, 1.65). The aHRs (95% CIs) of various outcomes were cancer,
      0.84 (0.68, 1.03); lymphoproliferative malignancy specifically, 0.51 (0.28,
      0.95); all other serious adverse events, 0.70 (0.56, 0.87) and cardiac events
      specifically, 0.52 (0.37, 0.72). CONCLUSION: There was no evidence of adverse
      outcome from long-term exposure to ETN. There was evidence of improved survival,
      reduced cardiovascular events and reduced lymphoproliferative malignancies.

PMID- 24140762
TI  - Hepatic CD141+IFNlambda+ DC subset: one against all?

PMID- 24140763
TI  - A ruptured aneurysm located at a collateral artery that extended from the
      proximal A2 segment to the M1 segment, associated with an anomalous branch of the
      anterior choroidal artery and middle cerebral artery hypoplasia: case report.
AB  - We here describe the first case of a ruptured aneurysm located at a collateral
      artery that extended from the proximal A2 segment to the M1 segment, which was
      associated with an anomalous branch of the anterior choroidal artery and middle
      cerebral artery (MCA) hypoplasia. The aneurysm was revealed by angiograms and
      intraoperative findings. No previous accounts have been published of such an
      extremely rare vessel anomaly. In practice, this case highlights the urgent need
      to preoperatively recognize such vascular anomalies, as well as to better
      understand the collateral blood supply in cerebral ischemia associated with these
      MCA anomalies. Such knowledge will be helpful for planning optimal surgical
      procedures. 

PMID- 24140764
TI  - Multiple intracranial nodules associated with rheumatoid arthritis: case report.
AB  - A 71-year-old woman with active rheumatoid arthritis (RA) was referred to our
      department because of multiple intracranial nodules. On admission, the RA disease
      activity was very high even after the treatment of methotrexate in other
      hospital. She underwent open biopsy to confirm a histopathological diagnosis of
      the intracranial lesions. Surgical specimen mainly consisted of necrosis
      surrounded by epithelioid cells. The masses were reduced spontaneously in size
      without additional treatment. Eleven month later, the lesions were relapsed. She
      underwent treatment with corticosteroid, and the lesions were remarkably
      regressed. The clinical course and histological examination were compatible with
      rheumatoid nodule (RN). Intracranial RN is extremely rare and its clinical course
      is not completely understood. In active RA patients, RNs should be considered,
      and histological diagnosis is inevitable for following suitable treatment. 

PMID- 24140765
TI  - Solitary epicranial neurofibroma with NF1-related germline mutation: case report.
AB  - A 33-year-old male became aware of a painless soft mass in the left occipital
      region. His medical and family history were unremarkable for neurofibromatosis
      type 1 (NF1) or other genetic disorders. Physical examination showed no signs of
      NF1. Neurological and ophthalmological examinations found no abnormality. Cranial
      computed tomography showed an isodense mass located subcutaneously with irregular
      deformities in the adjacent occipital bone. Magnetic resonance (MR) imaging
      demonstrated that the lesion, 7.5 * 5.5 cm in diameter, was hypointense both on
      T1- and T2-weighted images and intensely enhanced after gadolinium infusion. The
      patient requested to remove the large mass. The subcutaneous tumor was well
      circumscribed, encapsulated, and less vascular, and resected en bloc. The
      histological diagnosis was neurofibroma without findings of cell atypia, whereas
      genomic exploration identified abnormal gains in NF1 gene, and resultant absence
      of neurofibromin, a protein coded on NF1 gene. Solitary neurofibromas in
      "clinically" non-NF1 patients may originate from the genomic changes in NF1 gene.

PMID- 24140766
TI  - Penetration of the optic nerve and falciform ligament by an internal carotid
      artery-ophthalmic artery aneurysm: case report.
AB  - We report a case of an internal carotid artery (ICA)-ophthalmic artery aneurysm
      with penetration of the opticnerve. In addition, this case penetrated the
      falciform ligament, which severely disturbed optic canal unroofing during
      surgery. This is the first reported case in which penetration of the optic nerve
      and falciform ligament has been shown. To remove the anterior clinoid process in
      this case, the ultrasonic bone curette was a useful tool. 

PMID- 24140767
TI  - Validity of single tract microelectrode recording in subthalamic nucleus
      stimulation.
AB  - In surgery for subthalamic nucleus (STN) deep brain stimulation (DBS), precise
      implantation of the lead into the STN is essential. Physiological refinement with
      microelectrode recording (MER) is the gold standard for identifying STN. We
      studied single tract MER findings and surgical outcomes and verified our surgical
      method using single tract MER. The number of trajectories in MER and the final
      position of lead placement were retrospectively analyzed in 440 sides of STN DBS
      in 221 patients. Bilateral STN DBS yielded marked improvement in the motor score,
      dyskinesia/fluctuation score, and reduced requirement of dopaminergic medication
      in this series. The number of trajectories required to obtain sufficient activity
      of the STN was one in 79.0%, two in 18.2%, and three or more in 2.5% of 440
      sides. In 92 sides requiring altered trajectory, the final direction of
      trajectory movement was posterior in 73.9%, anterior in 13.0%, lateral in 5.4%,
      and medial in 4.3%. In 18 patients, posterior moves were required due to
      significant brain shift with intracranial air caused by outflow of CSF during the
      second side procedure. Sufficient STN activity is obtained with minimum
      trajectories by proper targeting and precise interpretation of MER findings even
      in the single tract method. Anterior-posterior moves rather than medial-lateral
      moves should be attempted first in cases with insufficient recording of STN
      activity. 

PMID- 24140768
TI  - Long-term seizure outcome following resective surgery for epilepsy: to be or not
      to be completely cured?
AB  - Surgical intervention is expected to improve the quality of life in patients with
      intractable epilepsy by providing adequate seizure control. Although many
      previous studies showed various rates of seizure freedom, definite conclusions
      have not yet been made regarding outcomes. In order to clarify the long-term
      postoperative outcome for a period up to 10 years, a retrospective review of our
      patients was performed longitudinally by using the survival analysis method. The
      postoperative state of epilepsy in 76 patients who underwent resection surgery
      was assessed based on Engel's criteria. In addition, Kaplan-Meier survival
      analysis was used to calculate the probability of seizure freedom. In this
      patient group, abnormal lesion were detected by MRI in 70 out of 76 cases, and
      the ictal onset zone was finally identified within temporal lobe in 51 cases. The
      most favorable outcome, defined as Engel Class Ia, was observed in 26 (37%), 24
      (40%), and 18 (41%) cases at 2, 5, and 10 years after surgery, respectively. The
      Kaplan-Meier survival curve in the overall group estimated the probability of
      seizure freedom as 75% (95% confidence interval [CI] 70-80%), 67% (62-72%), and
      51% (45-57%) at 2, 5, and 10 years follow up, respectively. Half of all seizure
      recurrences occurred within the first 2 postoperative years. In this study, we
      showed that long-term favorable outcome of seizure control following resection
      surgery can be achieved in more than half of the patients. 

PMID- 24140769
TI  - Which is the most appropriate disconnection surgery for refractory epilepsy in
      childhood?
AB  - Children with unilobar or multilobar pathology issuing in refractory epilepsy are
      potential candidates for surgical treatment. Extensive surgery results in good
      seizure control, but it also increases the risk of neurological deficits as well
      as motor and mental problems. We reviewed the cases of 19 children with
      refractory epilepsy treated surgically at Osaka University Hospital. Four of the
      19 patients underwent temporal disconnection, 2 underwent occipital lobectomy, 4
      underwent temporoparietooccipital disconnection, 6 underwent functional
      hemispherotomy, and 3 underwent corpus callosotomy. A good surgical outcome,
      i.e., Engel's class I or II, was achieved in 12 (63%) of the 19 patients.
      Excellent surgical outcomes and satisfactory motor and mental development were
      achieved in 4 patients who underwent temporoparietooccipital disconnection. The
      outcomes of functional hemispherectomy were also satisfactory. The outcomes of
      temporal disconnection and corpus callosotomy were poor in comparison to outcomes
      of the other procedures. We believe that better surgical outcomes would have been
      achieved with temporoparietooccipital disconnection in some cases treated by
      temporal disconnection or occipital resection. Adequate extensive surgical
      procedures should be considered for refractory childhood epilepsy arising from
      unilobar or multilobar pathology. 

PMID- 24140770
TI  - Retrospective analysis of bevacizumab in combination with ifosfamide,
      carboplatin, and etoposide in patients with second recurrence of glioblastoma.
AB  - Bevacizumab has been reported to be effective for recurrent glioblastoma. In our
      hospital, ifosfamide, carboplatin, etoposide (ICE) is the second-line
      chemotherapy for first recurrence of glioblastoma after temozolomide failure. In
      the present analysis, we retrospectively investigated the feasibility and
      effectiveness of bevacizumab combined with ICE in patients with glioblastoma at
      second relapse during ICE treatment. Between 2010 and 2012, tumor progressions
      were diagnosed in consecutive 8 patients who were treated with ICE for the first
      recurrence of glioblastoma. These patients were administered 3 cycles of 10 mg/kg
      bevacizumab every two weeks in combination with ICE treatment. The objective
      response rate of bevacizumab combination was 75% in Neuro-Oncology Working Group
      (RANO criteria), including complete response and partial response. Median
      progression free survival (PFS) and median overall survival (OS) after second
      relapse were 3.7 months (95% confidence interval [CI], 2.5-18.5 months) and 6.0
      months (95% CI, 3.2-19.7 months), respectively. The 6-month PFS rates were 25%
      (95% CI, 0-55.0%). The median OS after initial diagnosis was 23.3 months (95% CI,
      16.2-55.8 months). The grade 2 or 3 hematologic adverse events were identified in
      7 of 8 patients, most of which might be due to ICE chemotherapy. The results of
      our retrospective analysis suggest that combination treatment with bevacizumab
      and ICE may be safe and beneficial in patients with recurrent glioblastoma. 

PMID- 24140771
TI  - New treatment strategies to eradicate cancer stem cells and niches in
      glioblastoma.
AB  - Glioblastoma multiforme (GBM) harbors are not only rapidly dividing cells but
      also small populations of slowly dividing and dormant cells with tumorigenesity,
      self-renewal, and multi-lineage differentiation capabilities. Known as
      glioblastoma stem cells (GSCs), they are resistant to conventional chemo- and
      radiotherapy and may be a causative factor in recurrence. The treatment outcome
      in patients with GBM remains unsatisfactory and their mean survival time has not
      improved sufficiently. We studied clinical evidence and basic research findings
      to assess the possibility of new treatment strategies that target GSCs and their
      specific microenvironments (GBM niches) and raise the possibility of adding new
      treatments to eradicate GSCs and GBM niches. 

PMID- 24140773
TI  - Posterior auricular artery-middle cerebral artery bypass: a rare superficial
      temporal artery variant with well-developed posterior auricular artery-case
      report.
AB  - The posterior auricular artery (PAA) is one of the branches of the external
      carotid artery, but is usually too small for use as a donor artery for middle
      cerebral artery (MCA) territory revascularization. An extremely unusual case of
      PAA-MCA anastomosis was performed in a patient requiring MCA territory
      revascularization because the superficial temporal artery (STA) parietal branch
      was absent and the PAA was large enough. A 65-year-old man developed mild motor
      weakness in the right extremities caused by multiple small infarctions. Single
      photon emission computed tomography (CT) revealed deterioration of the vascular
      reserve capacity in the left MCA area. Cerebral angiography showed severe
      stenosis in the C2 portion of the left internal carotid artery, absence of the
      parietal branch of the left STA, and a well-developed PAA extending to the
      parietal area. The patient underwent STA (frontal branch)-MCA and PAA-MCA double
      anastomosis, and has suffered no stroke or transient ischemic attack. The STA
      with no bifurcation is known as a rare variation. The PAA also occurs with size
      variations but well-developed PAA is thought to be extremely rare. PAA can be
      used as a donor artery for MCA territory revascularization if the vessel size is
      suitable. Preoperative evaluation of the anatomy is mandatory for harvesting the
      arteries. 

PMID- 24140772
TI  - Dendritic cell-based immunotherapy for glioma: multiple regimens and implications
      in clinical trials.
AB  - High grade glioma is a highly invasive brain tumor and recurrence is almost
      inevitable, even after radical resection of the tumor mass. Cytotoxic immune
      responses and immunological memory induced by immunotherapy might prevent tumor
      recurrence. Dendritic cells (DCs) are professional antigen-presenting cells of
      the innate immune system with the potential to generate robust antigen-specific T
      cell immune responses. DC-based immunotherapeutic strategies have been
      intensively studied in both preclinical and clinical settings. Although advances
      have been made in the experimental use of DCs, there are still considerable
      challenges that need to be addressed for clinical translation. In this review, we
      describe the variability of regimens currently available for DC-based
      immunotherapy and then review strategies to optimize DC therapeutic efficacy
      against glioma. 

PMID- 24140774
TI  - Subarachnoid hemorrhage after an ischemic attack due to a bacterial middle
      cerebral artery dissecting aneurysm: case report and literature review.
AB  - A 78-year-old woman suffered sudden-onset left hemiparesis. There were no
      remarkable infectious findings. Computed tomography (CT) demonstrated a low
      intensity area supplied by the right middle cerebral artery (MCA). The diagnosis
      was cerebral ischemia and she was conservatively treated with hyperosmotic
      fluids. Two days after the ischemic stroke she suddenly became comatose. CT
      showed diffuse subarachnoid hemorrhage (SAH) in the basal cistern associated with
      a right intra-Sylvian and a right frontal subcortical hematoma. Three-dimensional
      (3D)-CT angiography demonstrated occlusion of the M2 portion of the right MCA.
      Four days after the ischemic onset she died of brain herniation. Autopsy revealed
      arterial dissection in the intermediate membrane of the right MCA bifurcation and
      occlusion of the M2 portion of the thrombosed right MCA. Gram staining showed
      remarkable bacterial infection in the thrombus. SAH after an ischemic attack due
      to MCA dissection is extremely rare. We suspect that bacterial infection was
      involved in the formation of her fragile dissecting aneurysm. 

PMID- 24140775
TI  - Atypical hemorrhagic presentation of a fourth ventricle subependymoma: case
      report.
AB  - OBJECTIVE: To present a case of a fourth ventricle subependymoma (SE) with a
      spontaneous acute subarachnoid intra-cisternal bleeding. METHODS: A 33-year-old
      man was admitted with 5 days history of oppressive occipital headache and neck
      pain without additional neurological focus. Unenhanced computed tomography (CT)
      scan demonstrated an isointense mass located in the fourth ventricle with a
      spontaneously hyperdense acute extratumoral hemorrhage in the cisterna magna.
      Contrast-enhanced magnetic resonance imaging (MRI) revealed a well-delimitated
      non-enhanced tumor, hypointense on T1-weighted and hyperintense on T2-weighted
      images, involving the floor of the fourth ventricle and extending caudally into
      the cervical spinal canal via foramen magnum. RESULTS: Intraoperative, a large
      blood clot was removed and a macroscopically hypovascularlesion was completely
      excised from the right lateral recess and the floor of the fourth ventricle.
      Intra and postoperative immuno-histopathological examination revealed a SE. The
      patient has a normal postoperative course and was discharged in the fifth
      postoperative day. A 10-month postoperative MRI study confirmed a complete tumor
      resection. CONCLUSION: Symptomatic SEs should be surgically treated emphasizing
      the urgency in the presence of hemorrhage. The interest of this case is to
      demonstrate that infratentorial SEs although extremely rare, might present with
      acute subarachnoid bleeding.

PMID- 24140776
TI  - A case of thrombosed giant aneurysm of the azygos anterior cerebral artery:
      clipping under monitoring of motor evoked potentials of the lower extremities.
AB  - Giant aneurysms of the distal anterior cerebral artery (ACA), especially the
      azygos ACA, are rare. We treated a patient with giant aneurysm of the azygos ACA
      who underwent aspiration of thrombus and clipping under monitoring of motor
      evoked potentials of the lower extremities (L-MEPs), resulting in remarkable
      recovery of motor and intellectual function. A 72-year-old male was admitted with
      left motor weakness persisting for 2 weeks. Neurologically, disorientation and
      intellectual impairment were also noted. Imaging disclosed a 60-mm diameter
      aneurysm with heterochronous thrombi arising from the distal bifurcation of the
      azygos ACA. One month after the onset, radical surgery was scheduled. The azygos
      ACA was secured and the aneurysm was dissected, and the distal parts of the
      azygos ACA were confirmed. After removal of the thrombus, the neck was
      reconstructed with eight clips. L-MEPs disappeared due to occlusion of the azygos
      ACA for 20 minutes but reappeared after 22 minutes and normalized 78 minutes
      after reperfusion. Motor weakness improved entirely with mini-mental state
      examination score of 29 points at 1 month after surgery. One year later, Wechsler
      Adult Intelligence Scale-Third Edition and Wechsler Memory Scale-Revised scores
      reached normal levels. Review of reported cases found this aneurysm tends to
      occur in males in their 50s to 70s presenting with mass sign. Decompression of
      the aneurysm in the frontal lobe and monitoring of L-MEPs during temporary
      occlusion of the ACA are important. 

PMID- 24140777
TI  - Preservation of the long insular artery to prevent postoperative motor deficits
      after resection of insulo-opercular glioma: technical case reports.
AB  - Resection of insulo-opercular gliomas carries the risk of postoperative
      hemiparesis caused by ischemia of the corona radiata resulting from injury to the
      long insular arteries. However, intraoperative identification of these
      perforating arteries is challenging. We attempted intra-operative motor evoked
      potential (MEP) monitoring under temporary occlusion of the suspected long
      insular artery arising from the opercular portion of middle cerebral artery in
      two patients with insulo-opercular gliomas. Temporary occlusion of the artery
      caused decrease in MEP amplitude, which recovered after release in one patient,
      who had no postoperative motor deficits or ischemic lesion in the corona radiata.
      Temporary occlusion of the artery caused no changes in MEP amplitude, so that the
      artery was sacrificed for tumor removal in the other patient, who had no motor
      deficits but ischemic lesion was present in the corona radiata in the territory
      of the long insular artery sparing the descending motor pathway. These cases show
      that great care should be taken during surgical manipulations near the posterior
      part of the superior limiting sulcus to preserve the perforating branches to the
      corona radiata, and temporary occlusion of the branches under MEP monitoring is
      useful to identify the arteries supplying the pyramidal tract. 

PMID- 24140778
TI  - Intraoperative computed tomography for cervicomedullary decompression of foramen
      magnum stenosis in achondroplasia: two case reports.
AB  - The authors report two cases of cervicomedullary decompression of foramen magnum
      (FM) stenosis in children with achondroplasia using intraoperative computed
      tomography (iCT). A 14-month-old girl with myelopathy and retarded motor
      development, and a 10-year-old girl who had already undergone incomplete FM
      decompression was presented with myelopathy. Both patients underwent
      decompressive sub-occipitalcraniectomy and C1 laminectomy without duraplasty
      using iCT. It clearly showed the extent of FM decompression during surgery, which
      finally enabled sufficient decompression. After the operation, their myelopathy
      improved. We think that iCT can provide useful information and guidance for
      sufficient decompression for FM stenosis in children with achondroplasia. 

PMID- 24140779
TI  - Surgical treatment of Chiari I malformation with ventricular dilation.
AB  - Ventricular dilation affects 7% to 10% of patients with Chiari type I
      malformation (CIM), but the choice of surgical treatment is controversial. To
      study the surgical approaches for treating CIM with ventricular dilation and to
      evaluate the efficacy of posterior fossa decompression (PFD), clinical and
      imaging data of 38 adult patients who received surgical correction performed at
      the authors' department from 2004 to 2011 were reviewed. Ventricular dilation was
      defined as Evans' index > 0.30. Preoperative fundus examinations were done on all
      patients and no papilledema was found. Surgical procedures included a sub
      occipital decompression and a C1 laminectomy, followed by a duraplasty with an
      autologous graft. Evans' index was measured before and after surgery
      respectively, and a paired samples t-test was performed to examine the
      difference. Factors predicting outcomes were investigated using logistic
      regression analysis. Follow-up was done to all patients with an average duration
      of 43 months. All postoperative magnetic resonance (MR) images showed a relief of
      cervicomedullary compression and recreation of the cisterna magna. Symptoms
      improved in 33 patients (86.8%), remained stable in 5 (13.2%), and no patient
      deteriorated. No significant change in ventricular size was observed after
      surgery (P = 0.257). Regression analysis showed duration of illness had a
      significant effect on clinical outcome (P = 0.034, OR = 12.5, 95% CI: 1.214,
      128.661). Our study suggests that the intracranial pressure (ICP) of patients
      with CIM and ventricular dilation is usually normal. PFD with duraplasty is an
      effective and safe treatment for CIM with ventricular dilation. Treatment of
      ventricular dilation is unnecessary before PFD as long as there is no persistent
      headache, vomiting, and papilledema. 

PMID- 24140780
TI  - The pitfalls in surgical management of lumbar canal stenosis associated with
      rheumatoid arthritis.
AB  - There have been few clinical studies in the area of cervical spine that focused
      on surgery for treating degenerative lumbar disease in patients with rheumatoid
      arthritis (RA). High rates of wound complications and instrumentation failure
      have been reported more for RA than for non-RA patients, although clinical
      outcomes are similar between the two groups. Lumbar canal stenosis in RA is
      caused not only by degeneration but also by RA-related spondylitis, which
      includes facet arthritis and inflammation around the vertebral endplate. The
      pitfalls in surgical management of lumbar canal stenosis in RA patients are
      highlighted in this study. The study reviewed 12 patients with RA, who were
      surgically treated for lumbar canal stenosis. Two out of five patients with
      pulmonary fibrosis died of worsened pulmonary condition, even though there were
      no perioperative pulmonary complications. Two patients with pedicle screw
      fixation showed no instrumentation failure, but two patients with spinous process
      fixation needed re-operation or vertebral fracture. Surgical treatment for lumbar
      canal stenosis in RA patients needs to be individually adjusted. Preoperative
      assessments and treatments of pulmonary fibrosis and osteopenia are essential.
      Surgery for lumbar canal stenosis with RA should be deferred for patients with
      advanced pulmonary fibrosis because of its potential life-threatening risk.
      Fusion surgery is indicated only in patients with kyphosis or severe symptoms
      caused by intervertebral instability. Pedicle screw fixation with hydroxyapatite
      granules or sublaminar tape is recommended. Closer follow-up after surgery is
      necessary because of possible delayed wound infection, instrumentation failure,
      pathological fracture, and respiratory deterioration. 

PMID- 24140781
TI  - Acetyl salicylic acid locally enhances functional recovery after sciatic nerve
      transection in rat.
AB  - Local effect of acetyl salicylic acid (ASA) on peripheral nerve regeneration was
      studied using a rat sciatic nerve transection model. Forty-five male healthy
      White Wistar rats were divided into three experimental groups (n = 15), randomly:
      Sham-operation (SHAM), control (SIL), and ASA-treated (SIL/ASA) groups. In SHAM
      group after anesthesia left sciatic nerve was exposed through a gluteal muscle
      incision and after homeostasis the muscle was sutured. In SIL group the left
      sciatic nerve was exposed the same way and transected proximal to tibio-peroneal
      bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted
      into a silicone tube and filled with 10 MUl phosphate buffered solution. In
      SIL/ASA group defect was bridged using a silicone tube filled with 10 MUl acetyl
      salisylic acid (0.1 mg/ml). Each group was subdivided into three subgroups of
      five animals each and were studied 4, 8, and 12 weeks after surgery. Data were
      analyzed statistically by factorial analysis of variance (ANOVA) and the
      Bonferroni test for pair-wise comparisons. Functional study confirmed faster and
      better recovery of regenerated axons in SIL/ASA than in SIL group (p < 0.05).
      Gastrocnemius muscle mass in SIL/ASA was significantly more than in SIL group.
      Morphometric indices of regenerated fibers showed that the number and diameter of
      the myelinated fibers in SIL/ASA were significantly higher than in control group.
      In immuohistochemistry, location of reactions to S-100 in SIL/ASA was clearly
      more positive than in SIL group. Response to local treatment of ASA demonstrates
      that it influences and improves functional recovery of peripheral nerve
      regeneration. 

PMID- 24140782
TI  - Surgical management of minimally invasive anterior lumbar interbody fusion with
      stand-alone interbody cage for L4-5 degenerative disorders: clinical and
      radiographic findings.
AB  - Surgical treatment for degenerative spinal disorders is controversial, although
      lumbar fusion is considered an acceptable option for disabling lower back pain.
      Patients underwent instrumented minimally invasive anterior lumbar interbody
      fusion (mini-ALIF) using a retroperitoneal approach except for requiring
      multilevel fusions, severe spinal canal stenosis, high-grade spondylolisthesis,
      and a adjacent segments disorders. We retrospectively reviewed the clinical
      records and radiographs of 142 patients who received mini-ALIF for L4-5
      degenerative lumbar disorders between 1998 and 2010. We compared preoperative and
      postoperative clinical data and radiographic measurements, including the modified
      Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for
      back and leg pain, disc height (DH), whole lumbar lordosis (WL), and vertebral
      wedge angle (WA). The mean follow-up period was 76 months. The solid fusion rate
      was 90.1% (128/142 patients). The average length of hospital stay was 6.9 days
      (range, 3-21 days). The mean blood loss was 63.7 ml (range, 10-456 ml). The mean
      operation time was 155.5 min (range, 96-280 min). The postoperative JOA and VAS
      scores for back and leg pain were improved compared with the preoperative scores.
      Radiological analysis showed significant postoperative improvements in DH, WL,
      and WA, and the functional and radiographical outcomes improved significantly
      after 2 years. The 2.8% complication rate included cases of wound infection,
      liquorrhea, vertebral body fractures, and a misplaced cage that required
      revision. Mini-ALIF was found to be associated with improved clinical results and
      radiographic findings for L4-5 disorders. A retroperitoneal approach might
      therefore be a valuable treatment option. 

PMID- 24140783
TI  - Treatment results of glioblastoma during the last 30 years in a single institute.
AB  - Treatment results of glioblastoma (GB) during the last 30 years in Tohoku
      University were analyzed to identify any improvements in patient outcome in all
      332 histologically proven cases of newly diagnosed GB treated consecutively in
      our department between 1982 and 2011. These 30 years was divided into 5 treatment
      eras, Group 1 (1982-1988, without preoperative evaluation by magnetic resonance
      [MR] imaging, n = 46), Group 2 (1989-1996, with preoperative MR imaging, n = 41),
      Group 3 (1997-1999, additionally underwent intraoperative functional brain
      mapping and neuronavigation system, n = 38), Group 4 (2000-August 2006, underwent
      30 Gy of whole brain radiation followed by 30 Gy of extended local accelerated
      hyperfractionated radiation therapy, n = 96), and Group 5 (September 2006-2011,
      adjuvant usage of temozolomide [TMZ], n = 111). Overall survival (OS) was
      calculated from the date of surgery to the death from any cause. The median
      survival time/2-year OS/5-year OS of Groups 1 to 5 were 10.7 months/10.9%/0%,
      17.3 months/26.2%/6.9%, 15.9 months/23.7%/5.3%, 20.1 months/34.8%/15.5%, and 20.9
      months/45.5%/19.7%. The prognosis for patients with GB improved significantly
      after the introduction of MR imaging. Younger GB, defined as patients aged below
      60 years, or total tumor resection with all ages in Group 5 had 5-year 0S of
      31.0% and 30.1%, respectively. The prognosis of GB was improved significantly
      after the introduction of TMZ for elderly GB, recursive partitioning analysis
      class 5, or totally resected GB. Introduction of MR imaging and TMZ, and total
      resection of the tumor were important in the improvement of outcome for patients
      with GB. 

PMID- 24140784
TI  - Positive effects of brown adipose tissue on femoral bone structure.
AB  - PURPOSE: Recent studies suggest a link between brown adipose tissue (BAT) and
      bone. The purpose of our study was to investigate the effects of BAT on femoral
      bone structure. MATERIALS AND METHODS: We studied 105 patients (19 m, 86 f. mean
      age 45.5+/-16.1 years) who underwent F18-FDG positron emission
      tomography/computed tomography (PET/CT) for benign etiologies (n=20) or follow-up
      of successfully treated malignancies (n=85); mean time between PET/CT and last
      form of treatment was 14.8+/-18.0 months. BAT volume by PET/CT; femoral bone
      structure by CT (total femoral cross-sectional area (CSA), cortical CSA); and
      thigh muscle CSA and thigh subcutaneous fat CSA by CT was assessed. RESULTS:
      There were positive correlations between BAT volume and total femoral CSA and
      cortical CSA, independent of age, BMI and history of malignancy (p<0.05). BAT
      volume correlated positively with thigh muscle CSA and thigh fat CSA (p<0.05).
      When total femoral CSA was entered as a dependent variable and BAT volume, age
      and BMI as independent variables in a forward stepwise regression model, BAT
      volume was the only predictor of total femoral CSA. When femoral cortical CSA was
      entered as a dependent variable and BAT volume, age and BMI as independent
      variables, BAT volume was the only predictor of femoral cortical CSA. CONCLUSION:
      BAT volume is a positive predictor of femoral bone structure and correlates
      positively with thigh muscle and subcutaneous fat, possibly mediated by muscle.
      These results provide further evidence of a positive effect of BAT on bone.

PMID- 24140786
TI  - Allocation of new growth between shoot, root and mycorrhiza in relation to
      carbon, nitrogen and phosphate supply: teleonomy with maximum growth rate.
AB  - Treating resource allocation within plants, and between plants and associated
      organisms, is essential for plant, crop and ecosystem modelling. However, it is
      still an unresolved issue. It is also important to consider quantitatively when
      it is efficient and to what extent a plant can invest profitably in a mycorrhizal
      association. A teleonomic model is used to address these issues. A six state
      variable model giving exponential growth is constructed. This represents carbon
      (C), nitrogen (N) and phosphorus (P) substrates with structure in shoot, root and
      mycorrhiza. The shoot is responsible for uptake of substrate C, the root for
      substrates N and P, and the mycorrhiza also for substrates N and P. A teleonomic
      goal, maximizing proportional growth rate, is solved analytically for the
      allocation fractions. Expressions allocating new dry matter to shoot, root and
      mycorrhiza are derived which maximize growth rate. These demonstrate several key
      intuitive phenomena concerning resource sharing between plant components and
      associated mycorrhizae. For instance, if root uptake rate for phosphorus is equal
      to that achievable by mycorrhiza and without detriment to root uptake rate for
      nitrogen, then this gives a faster growing mycorrhizal-free plant. However, if
      root phosphorus uptake is below that achievable by mycorrhiza, then a mycorrhizal
      association may be a preferred strategy. The approach offers a methodology for
      introducing resource sharing between species into ecosystem models. Applying
      teleonomy may provide a valuable short-term means of modelling allocation,
      avoiding the circularity of empirical models, and circumventing the complexities
      and uncertainties inherent in mechanistic approaches. However it is subjective
      and brings certain irreducible difficulties with it. 

PMID- 24140785
TI  - Turbo methanol extract inhibits bone resorption through regulation of T cell
      function.
AB  - Marine organisms have bioactive potential which has tremendous pharmaceutical
      promise. Emerging evidence highlights the importance of the interplay between
      bone and the immune system of which T lymphocytes and their product act as key
      regulators of bone resorption. In the present investigation we have analyzed the
      anti-osteoporotic effect of turbo methanol extract (TME) in the reversal of bone
      resoprtion. Forty-two female Swiss albino mice were used and randomly assigned
      into sham-operated group (sham) and six ovariectomized (OVX) subgroups, i.e. OVX
      with vehicle (OVX) that received daily oral administration of water ad libitum;
      OVX with estradiol (2mg/kg/day); and OVX with different doses of TME i.e. TME
      100mg/kg, TME 50mg/kg, TME 25mg/kg and TME 12.5mg/kg. Oral administration of TME
      or estradiol started on the second week after ovariectomy for a period of 4weeks.
      We observed that the administration of TME increased the trabeculation in tibia
      and reduced the atrophy in the uterus. TME significantly decreased the serum
      alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in OVX mice. Micro
      CT analysis revealed that the TME administration preserved the bone volume,
      connectivity density, trabecular number, trabecular thickness and trabecular
      separation in OVX mice. Bone mineralization was measured in different groups of
      mice by Raman spectroscopy. Reversal of bone resorption was observed in TME
      treated group of mice. To further investigate the mechanism of action of TME, we
      analyzed the T lymphocyte proliferation and profiles of cytokine TNFalpha and
      sRANKL in TME treated ovariectomized mice. Decrease in the elevation of T cell
      subsets was observed after the supplementation with TME. The extract
      significantly lowered the T cell proliferation responses to mitogens, phorbol 12
      myristate 13-acetate (PMA) and ionomycin (Io) and phytohemagglutinin (PHA). A
      marked reduction in TNFalpha and sRANKL secretion in serum and TNFalpha in cell
      free supernatants of activated T lymphocytes was observed upon TME
      administration. TME could significantly inhibit the in vitro osteoclastogenesis
      and the bone resorption observed using artificial calcium coated slides.
      Collectively, these results indicate that TME has the potential to inhibit bone
      resorption and may prove to be a potential candidate for the development of an
      anti-osteoporosis drug. 

PMID- 24140787
TI  - Improving the prediction accuracy of protein structural class: approached with
      alternating word frequency and normalized Lempel-Ziv complexity.
AB  - Prediction of protein structural class for low-similarity sequences remains a
      challenging problem. In this study, the new computational method has been
      developed to predict protein structural class by incorporating alternating word
      frequency and normalized Lempel-Ziv complexity. To evaluate the performance of
      the proposed method, jackknife cross-validation tests are performed on three
      widely used benchmark datasets, 25PDB, 1189 and 640, respectively. We report
      83.6%, 81.8% and 83.6% prediction accuracies for 25PDB, 1189 and 640 benchmarks,
      respectively. Comparison of our results with other methods shows that the
      proposed method is very promising and may provide a cost-effective alternative to
      predict protein structural class in particular for low-similarity datasets and
      may at least play an important complementary role to existing methods. 

PMID- 24140788
TI  - Under high stakes and uncertainty the rich should lend the poor a helping hand.
AB  - In social dilemmas, there is tension between individual incentives to optimize
      personal gain versus social benefits. An additional cause of conflict in such
      social dilemmas is heterogeneity. Cultural differences or financial inequity
      often interfere with decision making when a diverse group of individuals
      interact. We address these issues in situations where individuals are either rich
      or poor. Often, it is unclear how rich and poor individuals should interact -
      should the poor invest the same as the rich, or should the rich assist the poor?
      Which distribution of efforts can be considered as fair? To address the effects
      of heterogeneity on decisions, we model a collective-risk dilemma where players
      collectively have to invest more than a certain threshold, with heterogeneity and
      multiple rounds. We aim to understand the natural behavior and to infer which
      strategies are particularly stable in such asymmetric collective-risk games.
      Large scale individual based simulations show that when the poor players have
      half of the wealth the rich players posses, the poor contribute only when early
      contributions are made by the rich players. The rich contribute on behalf of the
      poor only when their own external assets are worth protecting. Under a certain
      degree of uncertainty we observe the rich maintain cooperation by assisting the
      poor. 

PMID- 24140789
TI  - Lack of correlation between in vitro antibiosis and in vivo protection against
      enteropathogenic bacteria by probiotic lactobacilli.
AB  - Increased resistance to infection is one of the beneficial effects attributed to
      probiotic microorganisms. This effect may be due to several mechanisms:
      production of inhibitory substances, blocking of adhesion sites on the intestinal
      surface, competition for nutrients and stimulation of mucosal and systemic
      immunity. The present study aimed to investigate the correlation between in vitro
      and in vivo antimicrobial activity of probiotic lactobacilli. The agar spot test
      was used to show that twenty Lactobacillus strains were able to inhibit the
      enteropathogenic bacterium Yersinia enterocolitica. This inhibition was mainly
      attributable to a decrease in pH resulting from dextrose fermentation by
      lactobacilli. The inhibition of Y. enterocolitica, Salmonella enterica serovar
      Typhimurium and Listeria monocytogenes by two probiotic strains, Lactobacillus
      casei C1 and Lactobacillus plantarum C4, was also associated with the pH
      decrease. However, both strains lacked protective effects in mouse experimental
      infection models, with the exception of long-lasting pre-treatment with L.
      plantarum C4, which exerted a partial protective effect against S. Typhimurium
      that was attributable to an immunostimulatory mechanism. Our results show that in
      vitro antibiosis tests do not provide useful information on the probiotic
      potential of Lactobacillus strains. 

PMID- 24140790
TI  - Diversity among strains of Pseudomonas aeruginosa from manure and soil, evaluated
      by multiple locus variable number tandem repeat analysis and antibiotic
      resistance profiles.
AB  - The results of a multiple locus variable number of tandem repeat (VNTR) analysis
      (MLVA)-based study designed to understand the genetic diversity of soil and
      manure-borne Pseudomonas aeruginosa isolates, and the relationship between these
      isolates and a set of clinical and environmental isolates, are hereby reported.
      Fifteen described VNTR markers were first selected, and 62 isolates recovered
      from agricultural and industrial soils in France and Burkina Faso, and from
      cattle and horse manure, along with 26 snake-related isolates and 17
      environmental and clinical isolates from international collections, were
      genotyped. Following a comparison with previously published 9-marker MLVA
      schemes, an optimal 13-marker MLVA scheme (MLVA13-Lyon) was identified that was
      found to be the most efficient, as it showed high typability (90%) and high
      discriminatory power (0.987). A comparison of MLVA with PFGE for typing of the
      snake-related isolates confirmed the MLVA13-Lyon scheme to be a robust method for
      quickly discriminating and inferring genetic relatedness among environmental
      isolates. The 62 isolates displayed wide diversity, since 41 MLVA types (i.e.
      MTs) were observed, with 26 MTs clustered in 10 MLVA clonal complexes (MCs).
      Three and eight MCs were found among soil and manure isolates, respectively. Only
      one MC contained both soil and manure-borne isolates. No common MC was observed
      between soil and manure-borne isolates and the snake-related or environmental and
      clinical isolates. Antibiotic resistance profiles were performed to determine a
      potential link between resistance properties and the selective pressure that
      might be present in the various habitats. Except for four soil and manure
      isolates resistant to ticarcillin and ticarcillin/clavulanic acid and one isolate
      from a hydrocarbon-contaminated soil resistant to imipenem, all environmental
      isolates showed wild-type antibiotic profiles. 

PMID- 24140791
TI  - FT-NIR spectroscopy and Whittaker smoother applied to joint analysis of duel
      components for corn.
AB  - Protein and total fat are two ingredients to measure the quality of corn. The aim
      of this study is to evaluate the quality of corn by the dual-component join
      determination through Fourier transform near infrared (FT-NIR) spectroscopic
      analysis. The calibration models were established by the systematic study
      performed respectively in the four regions of the whole range, the second
      overtone, the first overtone, and the combination. Whittaker smoother was
      introduced as an attractive alternative data preprocessing method. With the
      optimized parameters, Whittaker smoother indicates its priority for improving
      modeling results in any of the four regions. The predictive abilities were
      compared between the joint analysis of protein and total fat and the separate
      analysis of each single component by partial least squares (PLS) modeling. The
      uncertainty in parameter was further estimated for the linear models. It is
      suggested that the joint analysis of dual-component always leads to better
      predictive results, and also provided good evaluation results for the independent
      validation samples. For the joint analysis, the optimal region for protein was
      the combination (5400-4000 cm(-1)), and the optimal region for total fat was the
      first overtone (7200-5400 cm(-1)). The optimal PLS models also provided
      appreciate predictive performance for both protein and total fat. And the
      parameter uncertainty determination provided an acceptable estimate of the
      measured uncertainty for the FT-NIR analysis of corn. In general, the joint
      analysis of dual-component is a better strategy for FT-NIR analysis of corn, and
      it is hoped to be tested for other objects.

PMID- 24140792
TI  - A colorimetric and turn-on fluorescent chemosensor for Al(III) based on a
      chromone Schiff-base.
AB  - A simple Schiff-base receptor 7-methoxychromone-3-carbaldehyde-(pyridylformyl)
      hydrazone (MCNH) was prepared. It exhibits an "off-on-type" mode with high
      sensitivity in the presence of Al(3+). This compound could be used as Al(3+)
      probe in ethanol and it features visible light excitation (433 nm) and emission
      (503 nm) profiles. Upon binding of Al(3+), a significant fluorescence enhancement
      with a turn-on ratio over 800-fold was triggered. However, other metal ions had
      no such significant effect on the fluorescence. MCNH can also be used as a
      colorimetric chemosensor for Al(3+), which is easily observed from colorless to
      yellow-green by the naked-eye. The detection limit of MCNH for Al(3+) was as low
      as 1.9*10(-7) M.

PMID- 24140793
TI  - Preparation and characterization of nebivolol nanoparticles using Eudragit(r)
      RS100.
AB  - Nebivolol, a beta-blocker, has been widely used for the treatment of hypertension
      and cardiovascular diseases; but has drawbacks like poor solubility and
      bioavailability requiring frequent dosing. The present study attempts to overcome
      these issues through nanoparticulate delivery system using widely used carrier
      Eudragit((r)) RS100. The solvent evaporation (single emulsion) technique was used
      for developing nanoparticles. The impact of formulation and process variables on
      particle size and entrapment efficiency was studied to optimize the formulation.
      The physico-chemical characterization confirmed the particle size in nano range
      with smooth and spherical morphology. Further, Fourier transforms infrared (FTIR)
      spectroscopy and differential scanning calorimetry (DSC) studies confirm
      compatibility of drug-polymer combination. The in vitro drug release study of the
      prepared nanoparticles showed prolongation of drug release with reduced burst
      release in comparison with pure drug powder. 

PMID- 24140794
TI  - Application of docking methods for metal chelate affinity precipitation of endo
      glucanase using pH-response polymer.
AB  - An endo-glucanase could be efficiently purified using metal chelate affinity
      precipitation by a pH-response polymer PMMDN with iminodiacetic acid (IDA) and
      Cu(2+) as affinity ligand. In this study, docking method was used to identify the
      appropriate chelator and the metal ion as ligand by Grid score. The simulation
      results were compared with the label-free detection data analyzed by ForteBio's
      Octet. The ligand IDA-Cu(2+) was the final choice. A pH-response polymer PMMDN
      was polymerized and subsequently coupled with IDA-Cu(2+)as the ligand. The pI and
      recovery of PMMDN and PMMDN-IDA-Cu(2+) were 4.50, 99.8% and 4.39, 97.6%,
      respectively. Optimal adsorption conditions were found to be ligand density of
      3.0 mmol/g, pH 5.5 and 1.0 mol/L NaCl. The adsorption isotherm showed the maximum
      adsorption as 57.62 mg/g polymer and the dissociation constant as 1.08 mg/mL. For
      the elution of the PMMDN-IDA-Cu(2+) with the protein, 0.5 mol/L imidazole
      containing 1.0 mol/L guanidine hydrochloride was used as the eluent. Under these
      conditions, electrophoretic purity of endo-glucanase was obtained by only one
      step, and the elution recoveries were 96.45% (protein) and 93.24% (activity).

PMID- 24140795
TI  - Improvement of corrosion and biological properties of microarc oxidized coatings
      on Mg-Zn-Zr alloy by optimizing negative power density parameters.
AB  - Corrosion and biological properties of microarc oxidized calcium phosphate (CaP)
      coatings on Mg-Zn-Zr alloy were improved by optimizing negative power density
      parameters. Scanning electron microscope (SEM) and X-ray diffractometer (XRD)
      were employed to characterize the coating morphology and phase composition. The
      in vitro cytotoxicity and systemic toxicity tests were carried out to evaluate
      the coating biocompatibility. The degradability and bioactivity of the coatings
      were determined by in vitro simulated body fluid (SBF) immersion test. The
      coating microstructure, thickness and growth rate can be influenced by negative
      power density through changing direction of ions movements, rate of ions
      exchanges and affecting formation of plasma. The CaP coatings reduced the
      substrate degradation rate. Calcium phosphates, such as hydroxyapatite
      (Ca10(PO4)6(OH)2, HA) and calcium pyrophosphate (Ca2P2O7, CPP), etc., were
      induced after 30 days SBF immersion, indicating that the coatings have
      bioactivity. The CaP coatings have no toxicity to cell and living mice,
      indicating that the coatings are safe to serve as implants. 

PMID- 24140796
TI  - Fabrication of water-dispersible and biocompatible red fluorescent organic
      nanoparticles via PEGylation of aggregate induced emission enhancement dye and
      their cell imaging applications.
AB  - PEGylated red fluorescent organic nanoparticles (FONs) with aggregate induced
      emission enhancement (AIEE) properties have been prepared via self assembly of a
      cyano-substituted diarylethene derivate dye (C18-R) and synthetic copolymers,
      which were obtained by reversible addition-fragmentation chain transfer (RAFT)
      polymerization using stearyl methacrylate and poly(ethylene glycol) methacrylate
      as monomers. Thus obtained FONs were characterized by a series of techniques
      including transmission electron microscopy, Fourier transform infrared
      spectroscopy and fluorescent spectroscopy. To explore their potential biomedical
      applications, biocompatibility and cell uptake behavior of these red FONs were
      subsequently investigated. We demonstrated that FONs showed uniform morphology,
      suitable particle size (70-90 nm), high water dispersibility, strong red
      fluorescence and excellent biocompatibility, making them promising for bioimaging
      applications.

PMID- 24140797
TI  - Nanostructure determination from the pair distribution function: a parametric
      study of the INVERT approach.
AB  - We present a detailed study of the mechanism by which the INVERT method (Cliffe
      et al 2010 Phys. Rev. Lett. 104 125501) guides structure refinement of disordered
      materials. We present a number of different possible implementations of the
      central algorithm and explore the question of algorithm weighting. Our analysis
      includes quantification of the relative contributions of variance and fit-to-data
      terms during structure refinement, which leads us to study the roles of density
      fluctuations and configurational jamming in the RMC fitting process. We present a
      parametric study of the pair distribution function solution space for C60, a-Si
      and a-SiO2, which serves to highlight the difficulties faced in developing a
      transferable weighting scheme.

PMID- 24140798
TI  - Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system
      in the heart.
AB  - The hypertrophic growth of cardiac myocytes is a highly dynamic process that
      underlies physiological and pathological adaptation of the heart. Accordingly, a
      better understanding of the molecular underpinnings of cardiac myocyte
      hypertrophy is required in order to fully appreciate the causes and functional
      consequences of the changes in the size of the healthy and diseased heart.
      Hypertrophy is driven by increases in cardiac myocyte protein, which must be
      balanced by cellular ability to maintain protein quality in order to avoid
      maladaptive accumulation of toxic misfolded proteins. Recent studies have shown
      that the endoplasmic reticulum (ER), which, in cardiac myocytes, comprises the
      sarco/endoplasmic reticulum (SR/ER), is the site of most protein synthesis. Thus,
      the protein quality control machinery located at the SR/ER is likely to be an
      important determinant of whether the heart responds adaptively to hypertrophic
      growth stimuli. The SR/ER-transmembrane protein, ATF6, serves a critical protein
      quality control function as a first responder to the accumulation of potentially
      toxic, misfolded proteins. Misfolded proteins transform ATF6 into a transcription
      factor that regulates a gene program that is partly responsible for enhancing
      protein quality control. Two ATF6-inducible genes that have been studied in the
      heart and shown to be adaptive are RCAN1 and Derl3, which encode proteins that
      decrease protein-folding demand, and enhance degradation of misfolded proteins,
      respectively. Thus, the ATF6-regulated SR/ER protein quality control system is
      important for maintaining protein quality during growth, making ATF6, and other
      components of the system, potentially attractive targets for the therapeutic
      management pathological cardiac hypertrophy. This article is part of a Special
      Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and
      Autophagy". 

PMID- 24140799
TI  - Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning.
AB  - Remote ischemic preconditioning (RIPC) has emerged as a feasible and attractive
      therapeutic procedure for heart protection against ischemia/reperfusion (I/R)
      injury. However, its molecular mechanisms remain poorly understood. Hypoxia
      inducible factor-1alpha (HIF-1alpha) is a transcription factor that plays a key
      role in the cellular adaptation to hypoxia and ischemia. This study's aim was to
      test whether RIPC-induced cardioprotection requires HIF-1alpha upregulation to be
      effective. In the first study, wild-type mice and mice heterozygous for HIF1a
      (gene encoding the HIF-1alpha protein) were subjected to RIPC immediately before
      myocardial infarction (MI). RIPC resulted in a robust HIF-1alpha activation in
      the limb and acute cardioprotection in wild-type mice. RIPC-induced
      cardioprotection was preserved in heterozygous mice, despite the low HIF-1alpha
      expression in their limbs. In the second study, the role of HIF-1alpha in RIPC
      was evaluated using cadmium (Cd), a pharmacological HIF-1alpha inhibitor. Rats
      were subjected to MI (MI group) or to RIPC immediately prior to MI (R-MI group).
      Cd was injected 18 0min before RIPC (Cd-R-MI group). RIPC induced robust HIF
      1alpha activation in rat limbs and significantly reduced infarct size (IS).
      Despite Cd's inhibition of HIF-1alpha activation, RIPC-induced cardioprotection
      was preserved in the Cd-R-MI group. RIPC applied immediately prior to MI
      increased HIF-1alpha expression and attenuated IS in rats and wild-type mice.
      However, RIPC-induced cardioprotection was preserved in partially HIF1a-deficient
      mice and in rats pretreated with Cd. When considered together, these results
      suggest that HIF-1alpha upregulation is unnecessary in acute RIPC.

PMID- 24140800
TI  - Muscarinic stimulation and pinacidil produce similar facilitation of
      tachyarrhythmia induction in rat isolated atria.
AB  - Atrial tachyarrhythmias, the most common type of cardiac arrhythmias, are
      associated with greater stroke risk. Muscarinic cholinergic agonists have been
      shown to facilitate atrial tachyarrhythmia maintenance in the absence of cardiac
      disease. This has been attributed to action potential shortening, which enhances
      myocardial electrical anisotropy, and thus creates a substrate for reentrant
      excitation. In this study, we describe a similar effect of the ATP-sensitive K(+)
      channel (KATP) opener pinacidil on tachyarrhythmia induction in isolated rat
      atria. Pinacidil, which activates a weakly inwardly-rectifying current in
      isolated atrial myocytes, enhanced arrhythmia induction in the right and left
      atria. This effect was abolished by the KATP blocker glibenclamide, but not by
      atropine, which rules out a possible indirect effect due to stimulation of
      acetylcholine release. However, pinacidil attenuated carbachol-induced
      tachyarrhythmia facilitation, which may indicate that the action of these
      agonists converges to a common cellular mechanism. Both agonists caused marked
      action potential shortening in isolated atrial myocytes. Moreover, during
      arrhythmia in the presence of pinacidil and carbachol, the atrial
      vectorelectrographic patterns were similar and consistent with reentrant
      propagation of the electrical activity. From these results, we conclude that the
      KATP channel opening is pro-arrhythmic in atrial tissue, which may pose as an
      additional risk in the scenario of myocardial hypoxia. Moreover, the similarity
      of the electrophysiological effects of pinacidil and carbachol is suggestive that
      the sole increase in background K(+) conductance is sufficient for atrial
      tachyarrhythmia facilitation. 

PMID- 24140801
TI  - Dynamic cell-cell and cell-ECM interactions in the heart.
AB  - Recent studies have placed an increasing amount of emphasis on the cardiovascular
      system and understanding how the heart and its vasculature can be regenerated
      following pathological stresses, such as hypertension and myocardial infarction.
      The remodeling process involves the permanent cellular constituents of the heart
      including myocytes, fibroblasts, endothelial cells, pericytes, smooth muscle
      cells and stem cells. It also includes transient cell populations, such as immune
      cells (e.g. lymphocytes, mast cells and macrophages) and circulating stem cells.
      Following injury, there are dramatic shifts in the various cardiac cell
      populations that can affect cell-cell and cell-extracellular matrix interactions
      and cardiac function. Cardiac fibroblasts are a key component in normal heart
      function, as well as during the remodeling process through dynamic cell-cell
      interactions and synthesis and degradation of the extracellular matrix.
      Fibroblasts dynamically interact with the various cardiac cell populations
      through mechanical, chemical (autocrine and/or paracrine) and
      electrophysiological means to alter gene and protein expression, cellular
      processes and ultimately cardiac function. Better understanding these cell-cell
      and cell-extracellular matrix interactions and their biological consequences
      should provide novel therapeutic targets for the treatment of heart disease. In
      this review we discuss the nature of these interactions and the importance of
      these interactions in maintaining normal heart function, as well as their role in
      the cardiac remodeling process. This article is part of a Special Issue entitled
      "Myocyte-Fibroblast Signalling in Myocardium." 

PMID- 24140802
TI  - Slow-injection ultrasound-assisted emulsification-microextraction for
      determination of phthalate esters in water.
AB  - A type of ultrasound-assisted emulsification-microextraction (USAEME) was applied
      for the extraction and determination of four phthalate esters (e.g., dimethyl
      phthalate, diethyl phthalate, dibutyl phthalate and benzyl butyl phthalate) in
      aqueous samples prior to quantification using HPLC-UV. The simultaneous injection
      of the extraction solvent and ultrasonication of the mixture results in an
      efficient extraction with the extractant well-dispersed in the sample. The
      parameters affecting the experimental results were analyzed and optimized through
      the design of the experiment. Using a central composite face-centered design, the
      results of 28 experimental data points were analyzed and validated. An optimal
      set of operating conditions was obtained using 40 MUL of 1,1,2,2
      tetrachloroethane and 1% NaCl subjected to 2.0 min of ultrasonication under
      natural pH. Under optimized conditions, the extractions resulted in analyte
      recoveries of 75-87% and high enrichment factors of 356-415. The calibration
      curves were linear, and the correlation coefficients ranged from 0.9992 to 0.9997
      at concentrations of 5 to 300 MUg L(-1). The RSDs (n = 5) were 5.6-7.9%. The
      limits of detection for the four phthalate esters ranged from 0.26 to 1.46 MUg L(
      1). 

PMID- 24140804
TI  - High-sensitivity brain SPECT system using cadmium telluride (CdTe) semiconductor
      detector and 4-pixel matched collimator.
AB  - For high-sensitivity brain imaging, we have developed a two-head single-photon
      emission computed tomography (SPECT) system using a CdTe semiconductor detector
      and 4-pixel matched collimator (4-PMC). The term, '4-PMC' indicates that the
      collimator hole size is matched to a 2 * 2 array of detector pixels. By contrast,
      a 1-pixel matched collimator (1-PMC) is defined as a collimator whose hole size
      is matched to one detector pixel. The performance of the higher-sensitivity 4-PMC
      was experimentally compared with that of the 1-PMC. The sensitivities of the 1
      PMC and 4-PMC were 70 cps/MBq/head and 220 cps/MBq/head, respectively. The SPECT
      system using the 4-PMC provides superior image resolution in cold and hot rods
      phantom with the same activity and scan time to that of the 1-PMC. In addition,
      with half the usual scan time the 4-PMC provides comparable image quality to that
      of the 1-PMC. Furthermore, (99m)Tc-ECD brain perfusion images of healthy
      volunteers obtained using the 4-PMC demonstrated acceptable image quality for
      clinical diagnosis. In conclusion, our CdTe SPECT system equipped with the higher
      sensitivity 4-PMC can provide better spatial resolution than the 1-PMC either in
      half the imaging time with the same administered activity, or alternatively, in
      the same imaging time with half the activity. 

PMID- 24140803
TI  - The use of hemospray in portal hypertensive bleeding; a case series.
AB  - Hemospray is a haemostatic agent licensed for endoscopic haemostasis of non
      variceal upper gastrointestinal bleeding (NVUGIB) in Europe and Canada. Hemospray
      has been shown to be safe and effective in achieving haemostasis in bleeding
      peptic ulcers in a prospective clinical study and several further case series
      have described the use of hemospray in other non-variceal causes of
      gastrointestinal bleeding. Portal hypertensive gastropathy and colopathy are
      common in patients with portal hypertension. As hemospray is an easy to apply,
      non-contact method, which can cover large areas of mucosa, it may be of benefit
      in acute non-variceal portal hypertensive bleeding. We present data from the
      first four consecutive patients presenting to our institution with acute
      haemorrhage secondary to non-variceal diffuse portal hypertensive bleeding
      treated with hemospray. 

PMID- 24140805
TI  - Evaluation of ability of ferulic acid to control growth and fumonisin production
      of Fusarium verticillioides and Fusarium proliferatum on maize based media.
AB  - The aim of this study was to evaluate the efficacy of ferulic acid (1, 10, 20 and
      25 mM) at different water activity (aw) values (0.99, 0.98, 0.96 and 0.93) at 25 
      degrees C on growth and fumonisin production by Fusarium verticillioides and
      Fusarium proliferatum on maize based media. For both Fusarium species, the lag
      phase significantly decreased (p <= 0.001), and the growth rates increased (p <=
      0.001) at the lowest ferulic acid concentration used (1mM), regardless of the aw.
      However, high doses of ferulic acid (10 to 25 mM) significantly reduced (p <=
      0.001) the growth rate of both Fusarium species, regardless of the a(w). In
      general, growth rate inhibition increased as ferulic acid doses increased and as
      media aw decreased. Fumonisin production profiles of both Fusarium species showed
      that low ferulic acid concentrations (1-10mM) significantly increased (p <=
      0.001) toxin production, regardless of the aw. High doses of ferulic acid (20-25
      mM) reduced fumonisin production, in comparison with the controls, by both
      Fusarium species but they were not statistically significant in most cases. The
      results show that the use of ferulic acid as a post-harvest strategy to reduce
      mycotoxin accumulation on maize needs to be discussed.

PMID- 24140806
TI  - Development and validation of an extensive growth and growth boundary model for
      psychrotolerant Lactobacillus spp. in seafood and meat products.
AB  - A new and extensive growth and growth boundary model for psychrotolerant
      Lactobacillus spp. was developed and validated for processed and unprocessed
      products of seafood and meat. The new model was developed by refitting and
      expanding an existing cardinal parameter model for growth and the growth boundary
      of lactic acid bacteria (LAB) in processed seafood (O. Mejlholm and P. Dalgaard,
      J. Food Prot. 70. 2485-2497, 2007). Initially, to estimate values for the maximum
      specific growth rate at the reference temperature of 25  degrees C (MUref) and
      the theoretical minimum temperature that prevents growth of psychrotolerant LAB
      (T(min)), the existing LAB model was refitted to data from experiments with
      seafood and meat products reported not to include nitrite or any of the four
      organic acids evaluated in the present study. Next, dimensionless terms modelling
      the antimicrobial effect of nitrite, and acetic, benzoic, citric and sorbic acids
      on growth of Lactobacillus sakei were added to the refitted model, together with
      minimum inhibitory concentrations determined for the five environmental
      parameters. The new model including the effect of 12 environmental parameters, as
      well as their interactive effects, was successfully validated using 229 growth
      rates (MU(max) values) for psychrotolerant Lactobacillus spp. in seafood and meat
      products. Average bias and accuracy factor values of 1.08 and 1.27, respectively,
      were obtained when observed and predicted MU(max) values of psychrotolerant
      Lactobacillus spp. were compared. Thus, on average MU(max) values were only
      overestimated by 8%. The performance of the new model was equally good for
      seafood and meat products, and the importance of including the effect of acetic,
      benzoic, citric and sorbic acids and to a lesser extent nitrite in order to
      accurately predict growth of psychrotolerant Lactobacillus spp. was clearly
      demonstrated. The new model can be used to predict growth of psychrotolerant
      Lactobacillus spp. in seafood and meat products e.g. prediction of the time to a
      critical cell concentration of bacteria is considered useful for establishing the
      shelf life. In addition, the high number of environmental parameters included in
      the new model makes it flexible and suitable for product development as the
      effect of substituting one combination of preservatives with another can be
      predicted. In general, the performance of the new model was unacceptable for
      other types of LAB including Carnobacterium spp., Leuconostoc spp. and Weissella
      spp.

PMID- 24140807
TI  - Effect of buckwheat flour and oat bran on growth and cell viability of the
      probiotic strains Lactobacillus rhamnosus IMC 501(r), Lactobacillus paracasei IMC
      502(r) and their combination SYNBIO(r), in synbiotic fermented milk.
AB  - Fermented foods have a great significance since they provide and preserve large
      quantities of nutritious foods in a wide diversity of flavors, aromas and
      texture, which enrich the human diet. Originally fermented milks were developed
      as a means of preserving nutrients and are the most representatives of the
      category. The first aim of this study was to screen the effect of buckwheat flour
      and oat bran as prebiotics on the production of probiotic fiber-enriched
      fermented milks, by investigating the kinetics of acidification of buckwheat
      flour- and oat bran-supplemented milk fermented by Lactobacillus rhamnosus IMC
      501(r), Lactobacillus paracasei IMC 502(r) and their 1:1 combination named
      SYNBIO(r). The probiotic strains viability, pH and sensory characteristics of the
      fermented fiber-enriched milk products, stored at 4  degrees C for 28 days were
      also monitored. The results showed that supplementation of whole milk with the
      tested probiotic strains and the two vegetable substrates results in a
      significant faster lowering of the pH. Also, the stability of L. rhamnosus IMC
      501(r), L. paracasei IMC 502(r) and SYNBIO(r) during storage at 4  degrees C for
      28 days in buckwheat flour- and oat bran-supplemented samples was remarkably
      enhanced. The second aim of the study was to develop a new synbiotic product
      using the best combination of probiotics and prebiotics by promoting better
      growth and survival and be acceptable to the consumers with high concentration of
      probiotic strain. This new product was used to conduct a human feeding trial to
      validate the fermented milk as a carrier for transporting bacterial cells into
      the human gastrointestinal tract. The probiotic strains were recovered from fecal
      samples in 40 out of 40 volunteers fed for 4 weeks one portion per day of
      synbiotic fermented milk carrying about 10(9) viable cells.

PMID- 24140808
TI  - Microbial ecology of Vietnamese Tra fish (Pangasius hypophthalmus) fillets during
      processing.
AB  - There are numerous factors that can have an impact on the microbial ecology and
      quality of frozen Pangasius hypophthalmus fillets during processing in Vietnam.
      The presence of spoilage bacteria along the processing line can shorten the shelf
      life of thawed frozen fish products. Therefore, the spoilage microbiota
      throughout the processing chain of two companies (BC: large scale factory,
      chlorine-based process, BW: large scale factory, water-based process and SC:
      small scale factory, chlorine-based process) was identified by culture-dependent
      techniques and 16S rRNA gene sequencing. The microbiological counts were observed
      to be insignificantly different (p>0.05) between BC and BW. Surprisingly,
      chlorine treated fillets from the SC line were revealed to have significantly
      higher microbial counts than potable water treated fillets at BW line. This was
      determined to be a result of temperature abuse during processing at SC, with
      temperatures even greater than 10  degrees C being recorded from skinning
      onwards. On the contrary, the microbiota related to spoilage for BC and BW lines
      was determined by 16S rRNA gene sequencing to be more diverse than that on the SC
      line. A total of 174 isolates, 20 genera and 38 species were identified along the
      processing chains. The genera Aeromonas, Acinetobacter, Lactococcus and
      Enterococcus were prevalent at various processing steps on all the processing
      lines evaluated. A diverse range of isolates belonging to the Enterobacteriaceae
      such as Providencia, Shigella, Klebsiella, Enterobacter and Wautersiella were
      isolated from fillets sampled on the SC line whereas Serratia was only observed
      on fillets sampled on the BC and BW lines. The results can be used to improve
      Good Manufacturing Practices for processed Pangasius fillets and to select
      effective measures to prolong the shelf-life of thawed Vietnamese Pangasius
      fillets products.

PMID- 24140809
TI  - Functional activity of allatotropin and allatostatin in the pupal stage of a
      holometablous insect, Tribolium castaneum (Coleoptera, Tenebrionidae).
AB  - Allatotropin (AT) and allatostatin (AS) neuropeptides are known to regulate the
      biosynthesis of juvenile hormones (JH) in insects. Furthermore, they possess
      myoregulatory and other activities in a wide range of insect species. The genome
      of Tribolium castaneum encodes two AS and one AT precursors. Here we cloned the
      cDNAs of the precursors, followed their expression patterns during the pupal
      stage, and established their putative roles in adult development and oviposition
      of the females using RNA interference (RNAi). Cloning of the cDNA and gene
      structure analyses of the Tc-AT gene confirmed that the gene is expressed in
      three mRNA isoforms. Real-time PCR data demonstrate that the Tc-AT isoforms and
      the AS genes, Tc-AS C and Tc-AS B, are expressed in discerning developmental and
      tissue-specific patterns. Single injections of dsRNAi (targeted against the Tc
      AT, Tc-AS C, and Tc-AS B, respectively), into young pupae resulted in abnormal
      adult phenotypes, whereby about half of the animals (P1 phenotype) looked
      relatively normal, but the females laid low numbers of eggs. The other halves
      (P2) exhibited strong developmental defects with abnormal duration of the pupal
      stage, abnormal head and body sizes, short elytra, and incomplete sclerotization.
      Moreover, these females deposited no eggs and died within one week after
      emergence. Individual silencing of the Tc-AT mRNA isoforms showed that Tc-AT3 had
      the most disruptive influence on adult development and fecundity of the females.
      Our findings clearly indicate a significant role of AT and AS neuropeptides in
      the pupa. The distinct mechanisms of action, however, remain to be determined. 

PMID- 24140810
TI  - Memory biases in remitted depression: the role of negative cognitions at explicit
      and automatic processing levels.
AB  - BACKGROUND AND OBJECTIVES: Cognitive models propose that depression is caused by
      dysfunctional schemas that endure beyond the depressive episode, representing
      vulnerability factors for recurrence. However, research testing negative
      cognitions linked to dysfunctional schemas in formerly depressed individuals is
      still scarce. Furthermore, negative cognitions are presumed to be linked to
      biases in recalling negative self-referent information in formerly depressed
      individuals, but no studies have directly tested this association. In the present
      study, we evaluated differences between formerly and never-depressed individuals
      in several experimental indices of negative cognitions and their associations
      with the recall of emotional self-referent material. METHODS: Formerly (n = 30)
      and never depressed individuals (n = 40) completed measures of explicit (i.e.,
      scrambled sentence test) and automatic (i.e., lexical decision task) processing
      to evaluate negative cognitions. Furthermore participants completed a self
      referent incidental recall task to evaluate memory biases. RESULTS: Formerly
      compared to never depressed individuals showed greater negative cognitions at
      both explicit and automatic levels of processing. Results also showed greater
      recall of negative self-referent information in formerly compared to never
      depressed individuals. Finally, individual differences in negative cognitions at
      both explicit and automatic levels of processing predicted greater recall of
      negative self-referent material in formerly depressed individuals. LIMITATIONS:
      Analyses of the relationship between explicit and automatic processing indices
      and memory biases were correlational and the majority of participants in both
      groups were women. CONCLUSIONS: Our findings provide evidence of negative
      cognitions in formerly depressed individuals at both automatic and explicit
      levels of processing that may confer a cognitive vulnerability to depression.

PMID- 24140811
TI  - Attention bias for chocolate increases chocolate consumption--an attention bias
      modification study.
AB  - OBJECTIVE: The current study examined experimentally whether a manipulated
      attention bias for food cues increases craving, chocolate intake and motivation
      to search for hidden chocolates. METHOD: To test the effect of attention for food
      on subsequent chocolate intake, attention for chocolate was experimentally
      modified by instructing participants to look at chocolate stimuli ("attend
      chocolate" group) or at non-food stimuli ("attend shoes" group) during a novel
      attention bias modification task (antisaccade task). Chocolate consumption,
      changes in craving and search time for hidden chocolates were assessed. Eye
      movement recordings were used to monitor the accuracy during the experimental
      attention modification task as possible moderator of effects. Regression analyses
      were conducted to test the effect of attention modification and modification
      accuracy on chocolate intake, craving and motivation to search for hidden
      chocolates. RESULTS: Results showed that participants with higher accuracy (+1
      SD), ate more chocolate when they had to attend to chocolate and ate less
      chocolate when they had to attend to non-food stimuli. In contrast, for
      participants with lower accuracy (-1 SD), the results were exactly reversed. No
      effects of the experimental attention modification on craving or search time for
      hidden chocolates were found. LIMITATION: We used chocolate as food stimuli so it
      remains unclear how our findings generalize to other types of food. CONCLUSION:
      These findings demonstrate further evidence for a link between attention for food
      and food intake, and provide an indication about the direction of this
      relationship.

PMID- 24140812
TI  - Device artifact reduction for magnetic resonance imaging of patients with
      implantable cardioverter-defibrillators and ventricular tachycardia: late
      gadolinium enhancement correlation with electroanatomic mapping.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) of
      ventricular scar has been shown to be accurate for detection and characterization
      of arrhythmia substrates. However, the majority of patients referred for
      ventricular tachycardia (VT) ablation have an implantable cardioverter
      defibrillator (ICD), which obscures image integrity and the clinical utility of
      MRI. OBJECTIVE: The purpose of this study was to develop and validate a wideband
      LGE MRI technique for device artifact removal. METHODS: A novel wideband LGE MRI
      technique was developed to allow for improved scar evaluation on patients with
      ICDs. The wideband technique and the standard LGE MRI were tested on 18 patients
      with ICDs. VT ablation was performed in 13 of 18 patients with either endocardial
      and/or epicardial approach and the correlation between the scar identified on MRI
      and electroanatomic mapping (EAM) was analyzed. RESULTS: Hyperintensity artifact
      was present in 16 of 18 of patients using standard MRI, which was eliminated
      using the wideband LGE and allowed for MRI interpretation in 15 of 16 patients.
      All patients had ICD lead characteristics confirmed as unchanged post-MRI and had
      no adverse events. LGE scar was seen in 11 of 18 patients. Among the 15 patients
      in whom wideband LGE allowed visualization of myocardium, 10 had LGE scar and 5
      had normal myocardium in the regions with image artifacts when using the standard
      LGE. The left ventricular scar size measurements using wideband MRI and EAM were
      correlated with R(2) = 0.83 and P = .00003. CONCLUSION: Wideband LGE MRI improves
      the ability to visualize myocardium for clinical interpretation, which correlated
      well with EAM findings during VT ablation.

PMID- 24140813
TI  - Differences in passenger car and large truck involved crash frequencies at urban
      signalized intersections: an exploratory analysis.
AB  - The influence of intersection features on safety has been examined extensively
      because intersections experience a relatively large proportion of motor vehicle
      conflicts and crashes. Although there are distinct differences between passenger
      cars and large trucks-size, operating characteristics, dimensions, and weight
      modeling crash counts across vehicle types is rarely addressed. This paper
      develops and presents a multivariate regression model of crash frequencies by
      collision vehicle type using crash data for urban signalized intersections in
      Tennessee. In addition, the performance of univariate Poisson-lognormal (UVPLN),
      multivariate Poisson (MVP), and multivariate Poisson-lognormal (MVPLN) regression
      models in establishing the relationship between crashes, traffic factors, and
      geometric design of roadway intersections is investigated. Bayesian methods are
      used to estimate the unknown parameters of these models. The evaluation results
      suggest that the MVPLN model possesses most of the desirable statistical
      properties in developing the relationships. Compared to the UVPLN and MVP models,
      the MVPLN model better identifies significant factors and predicts crash
      frequencies. The findings suggest that traffic volume, truck percentage, lighting
      condition, and intersection angle significantly affect intersection safety.
      Important differences in car, car-truck, and truck crash frequencies with respect
      to various risk factors were found to exist between models. The paper provides
      some new or more comprehensive observations that have not been covered in
      previous studies. 

PMID- 24140815
TI  - Sternal replacement with a custom-made titanium plate after resection of a
      solitary breast cancer metastasis.
AB  - Bone is the most common metastatic site of breast cancer (BC) and sternal
      metastasis usually occurs in an isolated setting. We performed sternal
      reconstruction using a new total titanium custom-made neosternum after subtotal
      sternectomy for an isolated BC metastasis. Postoperative care was uneventful
      during a 7-day in-hospital stay. After a 6-month follow-up, the patient denied
      any shortness of breath, chest pain or limitation on her daily activities. The
      chest was stable without any paradoxical motion. Chest X-ray did not show any
      material fracture, pleural effusion or lung abnormalities. As it entails lower
      postoperative risk than previously existing reconstructive materials, the new
      material used in our sternal reconstruction may extend the existing range of
      indications of sternectomy for cancer with curative intent. 

PMID- 24140814
TI  - Developmental pattern of diacylglycerol lipase-alpha (DAGLalpha) immunoreactivity
      in brain regions important for song learning and control in the zebra finch
      (Taeniopygia guttata).
AB  - Zebra finch song is a learned behavior dependent upon successful progress through
      a sensitive period of late-postnatal development. This learning is associated
      with maturation of distinct brain nuclei and the fiber tract interconnections
      between them. We have previously found remarkably distinct and dense CB1
      cannabinoid receptor expression within many of these song control brain regions,
      implying a normal role for endocannabinoid signaling in vocal learning.
      Activation of CB1 receptors via daily treatments with exogenous agonist during
      sensorimotor stages of song learning (but not in adulthood) results in persistent
      alteration of song patterns. Now we are working to understand physiological
      changes responsible for this cannabinoid-altered vocal learning. We have found
      that song-altering developmental treatments are associated with changes in
      expression of endocannabinoid signaling elements, including CB1 receptors and the
      principal CNS endogenous agonist, 2-AG. Within CNS, 2-AG is produced largely
      through activity of the alpha isoform of the enzyme diacylglycerol lipase
      (DAGLalpha). To better appreciate the role of 2-AG production in normal vocal
      development we have determined the spatial distribution of DAGLalpha expression
      within zebra finch CNS during vocal development. Early during vocal development
      at 25 days, DAGLalpha staining is typically light and of fibroid processes.
      Staining peaks late in the sensorimotor stage of song learning at 75 days and is
      characterized by fiber, neuropil and some staining of both small and large cell
      somata. Results provide insight to the normal role for endocannabinoid signaling
      in the maturation of brain regions responsible for song learning and vocal-motor
      output, and suggest mechanisms by which exogenous cannabinoid exposure alters
      acquisition of this form of vocal communication. 

PMID- 24140816
TI  - Archibald Cochrane (1909-1988): the father of evidence-based medicine.
AB  - Professor Archibald Cochrane (1909-1988) is considered to be the originator of
      the idea of evidence-based medicine in our era. With his landmark book
      'Effectiveness and Efficiency: Random Reflections on Health services' he managed
      to inspire and positively influence the medical society with respect to the
      proper assessment of reliable evidence for the provision of the best medical
      care. His vision combined with his scientific achievements can be considered as
      the foundation of the Cochrane Collaboration; named after him in recognition of
      and gratitude for his pioneering work. We present the highlights of his
      adventurous and vibrant personal and academic life in an attempt to honour his
      contribution to shaping modern medical research. 

PMID- 24140817
TI  - Occupational class differences in body mass index and weight gain in Japan and
      Finland.
AB  - BACKGROUND: Occupational class differences in body mass index (BMI) have been
      systematically reported in developed countries, but the studies have mainly
      focused on white populations consuming a Westernized diet. We compared
      occupational class differences in BMI and BMI change in Japan and Finland.
      METHODS: The baseline surveys were conducted during 1998-1999 among Japanese (n =
      4080) and during 2000-2002 among Finnish (n = 8685) public-sector employees.
      Follow-up surveys were conducted among those still employed, in 2003 (n = 3213)
      and 2007 (n = 7086), respectively. Occupational class and various explanatory
      factors were surveyed in the baseline questionnaires. Linear regression models
      were used for data analysis. RESULTS: BMI was higher at baseline and BMI gain was
      more rapid in Finland than in Japan. In Finland, baseline BMI was lowest among
      men and women in the highest occupational class and progressively increased to
      the lowest occupational class; no gradient was found in Japan (country
      interaction effect, P = 0.020 for men and P < 0.0001 for women). Adjustment for
      confounding factors reflecting work conditions and health behavior increased the
      occupational class gradient among Finnish men and women, whereas factors related
      to social life had no effect. No statistically significant difference in BMI gain
      was found between occupational classes. CONCLUSIONS: The occupational class
      gradient in BMI was strong among Finnish employees but absent among Japanese
      employees. This suggests that occupational class inequalities in obesity are not
      inevitable, even in high-income societies.

PMID- 24140818
TI  - Ecologic correlations of selected food groups with disease incidence and
      mortality in Switzerland.
AB  - BACKGROUND: There is little information regarding the impact of diet on disease
      incidence and mortality in Switzerland. We assessed ecologic correlations between
      food availability and disease. METHODS: In this ecologic study for the period
      1970-2009, food availability was measured using the food balance sheets of the
      Food and Agriculture Organization of the United Nations. Standardized mortality
      rates (SMRs) were obtained from the Swiss Federal Office of Statistics. Cancer
      incidence data were obtained from the World Health Organization Health For All
      database and the Vaud Cancer Registry. Associations between food availability and
      mortality/incidence were assessed at lags 0, 5, 10, and 15 years by multivariate
      regression adjusted for total caloric intake. RESULTS: Alcoholic beverages and
      fruit availability were positively associated, and fish availability was
      inversely associated, with SMRs for cardiovascular diseases. Animal products,
      meat, and animal fats were positively associated with the SMR for ischemic heart
      disease only. For cancer, the results of analysis using SMRs and incidence rates
      were contradictory. Alcoholic beverages and fruits were positively associated
      with SMRs for all cancer but inversely associated with all-cancer incidence
      rates. Similar findings were obtained for all other foods except vegetables,
      which were weakly inversely associated with SMRs and incidence rates. Use of a 15
      year lag reversed the associations with animal and vegetal products, weakened the
      association with alcohol and fruits, and strengthened the association with fish.
      CONCLUSIONS: Ecologic associations between food availability and disease vary
      considerably on the basis of whether mortality or incidence rates are used in the
      analysis. Great care is thus necessary when interpreting our results.

PMID- 24140819
TI  - The influence of position and context on facial attractiveness.
AB  - It has been shown that a person's position in a group influences how that person
      is evaluated, with people in the middle perceived as more important than people
      on the fringe of a group. Four experiments examined whether the position of a
      face, in a line of five faces, influenced facial attractiveness. The middle
      position influenced the perceived attractiveness of the target face but the
      direction of this effect depended on the attractiveness of the target and the
      surrounding faces. Attractive faces were perceived as less attractive when in the
      middle of unattractive faces, or faces of average attractiveness. Conversely,
      unattractive faces were perceived as more attractive when in the middle of other
      unattractive faces. These results have wide implications, suggesting that the
      more central a stimulus is in a context then the greater the influence of the
      context on the judgment of that stimulus. 

PMID- 24140820
TI  - Differential impact of relevant and irrelevant dimension primes on rule-based and
      information-integration category learning.
AB  - Research has identified multiple category-learning systems with each being
      "tuned" for learning categories with different task demands and each governed by
      different neurobiological systems. Rule-based (RB) classification involves
      testing verbalizable rules for category membership while information-integration
      (II) classification requires the implicit learning of stimulus-response mappings.
      In the first study to directly test rule priming with RB and II category
      learning, we investigated the influence of the availability of information
      presented at the beginning of the task. Participants viewed lines that varied in
      length, orientation, and position on the screen, and were primed to focus on
      stimulus dimensions that were relevant or irrelevant to the correct
      classification rule. In Experiment 1, we used an RB category structure, and in
      Experiment 2, we used an II category structure. Accuracy and model-based analyses
      suggested that a focus on relevant dimensions improves RB task performance later
      in learning while a focus on an irrelevant dimension improves II task performance
      early in learning. 

PMID- 24140821
TI  - Sentencing, severity, and social norms: a rank-based model of contextual
      influence on judgments of crimes and punishments.
AB  - Context effects have been shown to bias lay people's evaluations of the severity
      of crimes and punishments. To investigate the cognitive mechanisms behind these
      effects, we develop and apply a rank-based social norms approach to judgments of
      perceived crime seriousness and sentence appropriateness. In Study 1, we find
      that (a) people believe on average that 84% of people illegally download software
      more than they do themselves and (b) their judged severity of, and concern about,
      their own illegal software downloading is predicted not by its amount but by how
      this amount is believed (typically inaccurately) to rank within a social
      comparison distribution. Studies 2 and 3 find that the judged appropriateness of
      a given sentence length is highly dependent on the length of other sentences
      available in the decision-making context: The same objective sentence was judged
      as approximately four times stricter when it was the second longest sentence
      being considered than when it was the fifth longest. It is concluded that the
      same mechanisms that are used to judge the magnitude of psychophysical stimuli
      bias judgments about legal matters. 

PMID- 24140822
TI  - An anxiety-induced bias in the perception of a bistable point-light walker.
AB  - Human sensitivity for social cues is exquisite, as illustrated by the ease with
      which simplified point-light movements invoke social and emotional responses.
      Compared to faces, these biological motion stimuli only recently started to be
      used to explore questions regarding social cognition and anxiety. We presented
      human point-light walkers that could be perceived as facing towards or facing
      away from the observer, and tested whether participants with high social anxiety
      would perceive these bistable stimuli differently, because this type of stimuli
      has particular relevance for them. The results showed that observers with high
      social anxiety tended to see walkers as facing away more frequently than those
      with low social anxiety. This may mean that high socially anxious observers are
      biased towards the more positive perceptual alternative because they are
      motivated to protect themselves against threatening social experiences, but we
      also explore alternative explanations. The findings are in line with the evidence
      for a positivity bias in perception, also called wishful seeing, but in contrast
      with the attentional negativity bias often found in social anxiety. We discuss
      reasons for this divergence and possible limitations of the current study. 

PMID- 24140823
TI  - Bilingual vocabulary size and lexical reading in Italian.
AB  - In the present study we investigated how the vocabulary size of English-Italian
      bilinguals affects reading aloud in Italian (L2) modulating the reader's
      sensitivity to lexical aspects of the language. We divided adult bilinguals in
      two groups according to their vocabulary size (Larger - LV, and smaller - SV),
      and compared their naming performance to that of native Italian (NI) readers. In
      Experiment 1 we investigated the lexicality and word frequency effects in reading
      aloud. Similarly to NI, both groups of bilinguals showed these effects. In
      Experiment 2 we investigated stress assignment - which is not predictable by rule
      - to Italian words. The SV group made more stress errors in reading words with a
      non-dominant stress pattern compared to the LV group. The results suggest that
      the size of the reader's L2 lexicon affects the probability of correct reading
      aloud. Overall, the results indicate that proficient adult bilinguals show a
      similar sensibility to the statistical and distributional properties of the
      language as compared to Italian monolinguals. 

PMID- 24140824
TI  - Rumination is characterized by valence-specific impairments in switching of
      attention.
AB  - The ability to flexibly switch attention between emotional and non-emotional
      information in working memory is considered important in stress-resilience and is
      impaired in mood disorders. A recent theory claims that this component of
      attention is specifically related to ruminative thought. To further investigate
      this claim we report two new experiments using the internal shift task (IST). In
      Experiment 1 (N=27) we examined the stability of switching ability measured using
      the IST through examination of internal consistency (stability within the task)
      and test-retest-reliability (stability over time) over two weeks. Results
      indicate relatively high stability of switching ability measured with the IST. In
      Experiment 2 the IST was administered to a pre-selected undergraduate sample of
      high (N=20) and low ruminators (N=20). The main findings were that rumination was
      related to attentional switching impairments, specifically in the context of
      emotional information. The switching impairments were most pronounced when
      negative information was held in working memory. The attentional switching
      impairments were most strongly related to the depressive brooding component of
      rumination. The results of this study lend further support to the proposed link
      between rumination and switching abilities. 

PMID- 24140825
TI  - Semantic interference in language production is due to graded similarity, not
      response relevance.
AB  - There is an ongoing debate on the question whether semantic interference effects
      in language production reflect competitive processes at the level of lexical
      selection or whether they reflect a post-lexical bottleneck, occupied in
      particular by response-relevant distractor words. To disentangle item-inherent
      categorical relatedness and task-related response relevance effects, we combined
      the picture-word interference task with the conditional naming paradigm in an
      orthogonal design, varying categorical relatedness and task-related response
      relevance independent of each other. Participants were instructed to name only
      objects that are typically seen in or on the water (e.g. canoe) and refrain from
      naming objects that are typically located outside the water (e.g. bike), and vice
      versa. Semantic relatedness and the response relevance of superimposed distractor
      words were manipulated orthogonally. The pattern of results revealed no evidence
      for response relevance as a major source of semantic interference effects in the
      PWI paradigm. In contrast, our data demonstrate that semantic similarity beyond
      categorical relations is critical for interference effects to be observed.
      Together, these findings provide support for the assumption that lexical
      selection is competitive and that semantic interference effects in the PWI
      paradigm reflect this competition.

PMID- 24140826
TI  - Perceiving vocal age and gender: an adaptation approach.
AB  - Aftereffects of adaptation have revealed both independent and interactive coding
      of facial signals including identity and expression or gender and age. By
      contrast, interactive processing of non-linguistic features in voices has rarely
      been investigated. Here we studied bidirectional cross-categorical aftereffects
      of adaptation to vocal age and gender. Prolonged exposure to young (~20yrs) or
      old (~70yrs) male or female voices biased perception of subsequent test voices
      away from the adapting age (Exp. 1) and the adapting gender (Exp. 2). Relative to
      gender-congruent adaptor-test pairings, vocal age aftereffects (VAAEs) were
      reduced but remained significant when voice gender changed between adaptation and
      test. This suggests that the VAAE relies on both gender-specific and gender
      independent age representations for male and female voices. By contrast, voice
      gender aftereffects (VGAEs) were not modulated by age-congruency of adaptor and
      test voices (Exp. 2). Instead, young voice adaptors generally induced larger
      VGAEs than old voice adaptors. This suggests that young voices are particularly
      efficient gender adaptors, likely reflecting more pronounced sexual dimorphism in
      these voices. In sum, our findings demonstrate how high-level processing of vocal
      age and gender is partially intertwined. 

PMID- 24140827
TI  - Electrochemiluminescence immunosensor for tumor markers based on biological
      barcode mode with conductive nanospheres.
AB  - A novel sandwich-type electrochemiluminescence (ECL) immunosensor was developed
      for highly sensitive and selective determination of tumor markers based on
      biological barcode mode. N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and the second
      antibody (Ab2) were simultaneously immobilized on conductive nanospheres to
      construct ABEI/Ab2-CNSs probes, which could form sandwich immunocomplex by Ab2
      and emit ECL signals by ABEI. The gold layer coated on the surface of the
      conductive nanospheres could extend the outer Helmholtz plane (OHP) of the ECL
      immunosensor effectively. Benefited from it, all ABEI molecules immobilized on
      conductive nanospheres would act as biological barcode to give in-situ ECL
      signals without interfering with the activity of the second antibody. In such a
      case, the sensitivity of the ECL immunosensor would be greatly improved because
      an antigen molecule would correspond to ECL signals of thousands of ABEI
      molecules. Using prostate specific antigen (PSA) as a model tumor marker, the ECL
      intensity was found to increase with the logarithm of PSA concentration with a
      wide linear range from 0.04 to 10 fg/mL. In addition, specificity, stability,
      reproducibility, regeneration and application were satisfactory. Therefore, this
      developed ECL immunosensor has a potential for practical detection of disease
      related proteins besides tumor markers in the clinical diagnostics.

PMID- 24140828
TI  - A new disposable electrode for electrochemical study of leukemia K562 cells and
      anticancer drug sensitivity test.
AB  - Developing cost-effective and simple analysis tools is of vital importance for
      practical applications in bioanalysis. In this work, a new disposable
      electrochemical cell sensor with low cost and simple fabrication was proposed to
      study the electrochemical behavior of leukemia K562 cells and the effect of
      anticancer drugs on cell viability. The analytical device was integrated by using
      ITO glass as the substrate of working electrodes and paper as the electrolytic
      cell. The cyclic voltammetry of the K562 cells at the disposable electrode
      exhibited an irreversible anodic peak and the peak current is proportional to the
      cell number. This anodic peak is attributed to the oxidation of guanine in cells
      involving two protons per transfer of two electrons. For the drug sensitivity
      tests, arsenic trioxide and cyclophosphamide were added to cell culture media. As
      a result, the electrochemical responses of the K562 cells decreased
      significantly. The cytotoxicity curves and results obtained corresponded well
      with the results of CCK-8 assays. In comparison to conventional methods, the
      proposed method is simple, rapid and inexpensive. More importantly, the developed
      sensor is supposed to be a single-use disposable device and electrodes were
      prepared "as new" for each experiment. We think that such disposable electrodes
      with these characteristics are suitable for experimental study with cancer cells
      or other types of pathogens for disease diagnosis, drug selection and on-site
      monitoring. 

PMID- 24140829
TI  - Integrating bipolar electrochemistry and electrochemiluminescence imaging with
      microdroplets for chemical analysis.
AB  - Here we develop a microdroplet sensor based on bipolar electrochemistry and
      electrochemiluminescence (ECL) imaging. The sensor was constructed with a closed
      bipolar cell on a hybrid poly(dimethylsioxane) (PDMS)-indium tin oxide (ITO)
      glass microchip. The ITO microband functions as the bipolar electrode and its two
      poles are placed in two spatially separate micro-reservoirs predrilled on the
      PDMS cover. After loading microliter-sized liquid droplets of tris(2,2'
      bipyridyl) ruthenium (II)/2-(dibutylamino) ethanol (Ru(bpy)3(2+)/DBAE) and the
      analyte to the micro-reservoirs, an appropriate external voltage imposed on the
      driving electrodes could induce the oxidation of Ru(bpy)3(2+)/DBAE and
      simultaneous reduction of the analyte at the anodic and cathodic poles,
      respectively. ECL images generated by Ru(bpy)3(2+)/DBAE oxidation at the anodic
      pole and the electrical current flowing through the bipolar electrode can be
      recorded for quantitative analyte detection. Several types of quinones were
      selected as model analytes to demonstrate the sensor performance. Furthermore,
      the cathodic pole of bipolar electrode can be modified with (3
      aminopropyl)triethoxysilane-gold nanoparticles-horseradish peroxidase composites
      for hydrogen peroxide detection. This microdroplet sensor with a closed bipolar
      cell can avoid the interference and cross-contamination between analyte solutions
      and ECL reporting reagents. It is also well adapted for chemical analysis in the
      incompatible system, e.g., detection of organic compounds insoluble in water by
      aqueous ECL generation. Moreover, this microdroplet sensor has advantages of
      simple structure, high sensitivity, fast response and wide dynamic response,
      providing great promise for chemical and biological analysis.

PMID- 24140830
TI  - Atmospheric pressure plasma polymers for tuned QCM detection of protein adhesion.
AB  - Our efforts have been concentrated in preparing plasma polymeric thin layers at
      atmospheric pressure grown on Quartz Crystal Microbalance-QCM electrodes for
      which the non-specific absorption of proteins can be efficiently modulated, tuned
      and used for QCM biosensing and quantification. Plasma polymerization reaction at
      atmospheric pressure has been used as a simple and viable method for the
      preparation of QCM bioactive surfaces, featuring variable protein binding
      properties. Polyethyleneglycol (ppEG), polystyrene (ppST) and poly(ethyleneglycol
      styrene) (ppST-EG) thin-layers have been grown on QCM electrodes. These layers
      were characterized by Atomic Force Microscopy (AFM), Contact angle measurements,
      Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The
      plasma ppST QCM electrodes present a higher adsorption of Concanavalin A (ConA)
      and Bovine Serum Albumin (BSA) proteins when compared with the commercial coated
      polystyrene (ppST) ones. The minimum adsorption was found for ppEG, surface,
      known by their protein anti-fouling properties. The amount of adsorbed proteins
      can be tuned by the introduction of PEG precursors in the plasma discharge during
      the preparation of ppST polymers.

PMID- 24140831
TI  - A label-free immunosensor based on graphene nanocomposites for simultaneous
      multiplexed electrochemical determination of tumor markers.
AB  - Here we prepared a label-free electrochemical immunosensor employing indium tin
      oxide (ITO) sheets as working electrodes and graphene nanocomposites as
      supporting matrix for simultaneous determination of carcinoembryonic antigen
      (CEA) and alpha-fetoprotein (AFP). Reduced graphene oxide/thionine/gold
      nanoparticles nanocomposites were synthesized and coated on ITO for the
      immobilization of anti-CEA while reduced graphene oxide/Prussian Blue/gold
      nanoparticles were used to immobilize anti-AFP. The immunosensor determination
      was based on the fact that due to the formation of antibody-antigen
      immunocomplex, the decreased response currents of thionine and Prussian Blue were
      directly proportional to the concentrations of corresponding antigens.
      Experimental results revealed that the multiplexed immunoassay enabled the
      simultaneous determination of CEA and AFP with linear working ranges of 0.01-300
      ng mL(-1). The limit of detections for CEA is 0.650 pg mL(-1) and for AFP is
      0.885 pg mL(-1). In addition, the methodology was evaluated for the analysis of
      clinical serum samples and received a good correlation with the enzyme linked
      immunosorbent assay.

PMID- 24140832
TI  - Enhanced nucleic acid amplification with blood in situ by wire-guided droplet
      manipulation (WDM).
AB  - There are many challenges facing the use of molecular biology to provide
      pertinent information in a timely, cost effective manner. Wire-guided droplet
      manipulation (WDM) is an emerging format for conducting molecular biology with
      unique characteristics to address these challenges. To demonstrate the use of
      WDM, an apparatus was designed and assembled to automate polymerase chain
      reaction (PCR) on a reprogrammable platform. WDM minimizes thermal resistance by
      convective heat transfer to a constantly moving droplet in direct contact with
      heated silicone oil. PCR amplification of the GAPDH gene was demonstrated at a
      speed of 8.67 s/cycle. Conventional PCR was shown to be inhibited by the presence
      of blood. WDM PCR utilizes molecular partitioning of nucleic acids and other PCR
      reagents from blood components, within the water-in-oil droplet, to increase PCR
      reaction efficiency with blood in situ. The ability to amplify nucleic acids in
      the presence of blood simplifies pre-treatment protocols towards true point-of
      care diagnostic use. The 16s rRNA hypervariable regions V3 and V6 were amplified
      from Klebsiella pneumoniae genomic DNA with blood in situ. The detection limit of
      WDM PCR was 1 ng/MUL or 10(5)genomes/MUL with blood in situ. The application of
      WDM for rapid, automated detection of bacterial DNA from whole blood may have an
      enormous impact on the clinical diagnosis of infections in bloodstream or chronic
      wound/ulcer, and patient safety and morbidity.

PMID- 24140833
TI  - Photoelectrochemical biosensing platform for microRNA detection based on in situ
      producing electron donor from apoferritin-encapsulated ascorbic acid.
AB  - A novel signal "on" type of photoelectrochemical biosensor for microRNA-21
      hybridization detection was fabricated, where Bi2S3 nanorods were used as
      photoactive material with a maximum adsorption at 450 nm visible light, hairpin
      structure DNA as detecting probe, streptavidin as signal capturing unit and
      biotin functionalized ascorbic acid loaded apoferritin as signal amplification
      unit. Hybridization between the probe and the target microRNA-21 was confirmed by
      the increased photocurrent of the biosensor after electron donor of ascorbic acid
      was introduced into the detection buffer by digesting the apoferritin by
      trypsase, indicating that this method could be used fProd. Type: FTPor
      quantitative measurements, and the discrimination of the complementary from
      mismatched microRNA-21. Under the optimal detection conditions, the
      photoelectrochemical biosensor displayed a linear range of 1-5000 fM and a low
      detection limit of 0.35 fM for microRNA-21 determination. Moreover, the down
      regulated expression of microRNA-21 in poultry cells and tissues infecting with
      avian leukosis viruses was confirmed by directly detecting microRNA-21 in
      extracted total RNA. This proposed strategy may open a new avenue for the
      applications of photoelectrochemical biosensor for oligonucleotides detection
      using visible light irradiation, which could largely reduce the destructive
      effect of UV light on biomolecules.

PMID- 24140834
TI  - Nanostructured alpha-MoO3 thin film as a highly selective TMA sensor.
AB  - Molybdenum trioxide thin films of different thicknesses were prepared on a glass
      substrate with the chemical spray pyrolysis technique. The X-ray diffraction
      pattern indicates the formation of an alpha-MoO3 phase with a polycrystalline
      nature. The field-emission scanning electron micrograph of the surface indicates
      nanostructured lamellar crystallites. The trimethylamine vapour sensing property
      of the film was studied by the chemiresistive method at room temperature (~ 30
      degrees C). Film with a thickness of 520 nm shows a response of 12% for 0.5 ppm
      of TMA vapour in 54% relative humidity, with response and recovery times of 32s
      and 15s, respectively. The detection limit and sensing response of the alpha-MoO3
      thin film in a mixed environment were analysed and reported.

PMID- 24140835
TI  - A hydrophilic polymer based microfluidic system with planar patch clamp electrode
      array for electrophysiological measurement from cells.
AB  - This paper presents a microfluidic planar patch clamp system based on a
      hydrophilic polymer poly(ethylene glycol) diacrylate (PEGDA) for whole cell
      current recording. The whole chip is fabricated by UV-assisted molding method for
      both microfluidic channel structure and planar electrode partition. This
      hydrophilic patch clamp chip has demonstrated a relatively high gigaseal success
      rate of 44% without surface modification compared with PDMS based patch clamp
      devices. This chip also shows a capability of rapid intracellular and
      extracellular solution exchange with high stability of gigaseals. The capillary
      flow kinetic experiments demonstrate that the flow rates of PEGDA microfluidic
      channels are around two orders of magnitude greater than those for PDMS-glass
      channels with the same channel dimensions. This hydrophilic polymer based patch
      clamp chips have significant advantages over current PDMS elastomer based systems
      such as no need for surface modification, much higher success rate of cell
      gigaseals and rapid solution exchange with stable cell gigaseals. Our results
      indicate the potential of these devices to serve as useful tools for
      pharmaceutical screening and biosensing tasks.

PMID- 24140836
TI  - Disposable immunosensor using a simple method for oriented antibody
      immobilization for label-free real-time detection of an oxidative stress
      biomarker implicated in cancer diseases.
AB  - This work proposes a novel approach for a suitable orientation of antibodies (Ab)
      on an immunosensing platform, applied here to the determination of 8-hydroxy-2'
      deoxyguanosine (8OHdG), a biomarker of oxidative stress that has been associated
      to chronic diseases, such as cancer. The anti-8OHdG was bound to an amine
      modified gold support through its Fc region after activation of its carboxylic
      functions. Non-oriented approaches of Ab binding to the platform were tested in
      parallel, in order to show that the presented methodology favored Ab/Ag affinity
      and immunodetection of the antigen. The immunosensor design was evaluated by
      quartz-crystal microbalance with dissipation, atomic force microscopy,
      electrochemical impedance spectroscopy (EIS) and square-wave voltammetry. EIS was
      also a suitable technique to follow the analytical behavior of the device against
      8OHdG. The affinity binding between 8OHdG and the antibody immobilized in the
      gold modified platform increased the charge transfer resistance across the
      electrochemical set-up. The observed behavior was linear from 0.02 to 7.0 ng/mL
      of 8OHdG concentrations. The interference from glucose, urea and creatinine was
      found negligible. An attempt of application to synthetic samples was also
      successfully conducted. Overall, the presented approach enabled the production of
      suitably oriented Abs over a gold platform by means of a much simpler process
      than other oriented-Ab binding approaches described in the literature, as far as
      we know, and was successful in terms of analytical features and sample
      application.

PMID- 24140837
TI  - Electrochemical sensing of glucose by carbon cloth-supported Co3O4/PbO2 core
      shell nanorod arrays.
AB  - A novel electrochemical sensor for the detection of glucose was constructed based
      on the use of Co3O4/PbO2 core-shell nanorod arrays as electrocatalysts. In this
      paper the Co3O4/PbO2 core-shell nanorod arrays grow directly on a flexible carbon
      cloth substrate by the combination of hydrothermal synthesis and electrochemical
      deposition methods. The as-prepared hierarchical nanocomposites show the
      structural characteristics of nanowire core and nanoparticle shell. The carbon
      cloth-supported Co3O4/PbO2 nanorod array electrode exhibits higher sensitivity
      (460.3 MUA mM(-1)cm(-2) in the range from 5 MUM to 1.2mM) and lower detection
      limit (0.31 MUM (S/N=3)) than the carbon cloth-supported Co3O4 nanowire array
      electrode. Both the three-dimensional network of carbon cloth substrate and the
      hierarchical nanostructure of binary Co3O4/PbO2 composites make such an electrode
      have high electrocatalytic activity towards the glucose oxidation. Due to the
      excellent sensitivity, repeatability and anti-interference ability, the carbon
      cloth-supported Co3O4/PbO2 nanorod arrays will be the promising materials for
      fabricating practical non-enzymatic glucose sensors.

PMID- 24140838
TI  - AKR1B10, a transcriptional target of p53, is downregulated in colorectal cancers
      associated with poor prognosis.
AB  - p53 is one of the most important tumor suppressor genes, and it is frequently
      inactivated in various cancers. p53 modulates various cellular functions, such as
      apoptosis and cell-cycle arrest via transcriptional regulation. Recently, p53 has
      been reported to be involved in a wide range of cellular metabolic pathways,
      including glycolysis, oxidative phosphorylation, glutaminolysis, and the
      antioxidant response. To understand the functional mechanism of p53, it is
      important to find out the direct transcriptional targets of p53. In this study,
      aldo-keto reductase family 1, member B10 (AKR1B10) was identified as a direct
      target of the p53 family by cDNA microarray analysis after comparing the mRNA
      expression of control and H1299 cells that overexpressed with p53 family members.
      In addition, we found that the expression of AKR1B10 was significantly decreased
      in colorectal cancers and adenomas as compared with normal colon tissues.
      Knockdown of AKR1B10 significantly inhibited p53-induced apoptosis in colorectal
      cancer cells, whereas the overexpression of AKR1B10 enhanced p53-induced
      apoptosis and inhibited tumor proliferation in vivo. Furthermore, low expression
      of AKR1B10 in colon cancer patients was correlated with decreased survival and
      poor prognosis. These results suggest that decreased expression of AKR1B10 could
      disrupt the tumor suppressive function of p53, which result in decreased survival
      in colorectal cancer patients. In summary, AKR1B10 may be a novel prognostic
      predictor and a novel therapeutic target for colorectal cancer. IMPLICATIONS:
      AKR1B10, a transcriptional target of p53, is also a novel prognostic and
      therapeutic molecule in colorectal cancer.

PMID- 24140839
TI  - The first 24 years of reverse Monte Carlo modelling, Budapest, Hungary, 20-22
      September 2012.

PMID- 24140840
TI  - Development of infant reaching behaviors: kinematic changes in touching and
      hitting.
AB  - This longitudinal study investigated the development of reaching in typical
      infants, from age 4 to 8 months, and described the pattern of hand kinematics
      underlying changes in the characteristics of infants' actions while reaching for
      a target. Thirteen infants were followed biweekly. Two reaching behaviors emerged
      during the infants' free interactions with the target, touching and hitting.
      Changes over time were documented for the number of movement units, straightness
      index, distance, peak velocity and time to peak velocity of the hand for touches
      and hits. We observed increases in the numbers of touches and hits and changes in
      hand kinematics over time; the distance traveled by the hand was greater for
      hitting compared to touching. These kinematic changes were specific to the
      movement patterns that infants adopted to reach to the target. 

PMID- 24140841
TI  - The Early Motor Questionnaire (EMQ): a parental report measure of early motor
      development.
AB  - Children's early motor skills are critical for development across language,
      social, and cognitive domains, and warrant close examination. However, examiner
      administered motor assessments are time consuming and expensive. Parent-report
      questionnaires offer an efficient alternative, but validity of parent report is
      unclear and only few motor questionnaires exist. In this report, we use cross
      sectional and longitudinal data to investigate the validity of parent report in
      comparison to two examiner-administered measures (Mullen Scales of Early
      Learning, MSEL; Peabody Developmental Motor Scales, PDMS-2), and introduce a new
      parent-report measure called the Early Motor Questionnaire (EMQ). Results
      indicate strong correlations between parent report on the EMQ and a child's age,
      robust concurrent and predictive validity of parent report with both the MSEL and
      PDMS-2, and good test-retest reliability of parent report on the EMQ. Together,
      our findings support the conclusion that parents provide dependable accounts of
      early motor and cognitive development. 

PMID- 24140842
TI  - From cleaning up to helping out: parental socialization and children's early
      prosocial behavior.
AB  - Relations between parental socialization and infants' prosocial behavior were
      investigated in sixty three 18- and 30-month old children. Parents' socialization
      techniques (e.g., directives, negotiation, reasoning) differed for the two age
      groups, as did relations between socialization and different forms of emerging
      prosocial behavior (helping; sharing). 

PMID- 24140843
TI  - Blood type, lymphadenectomy and blood transfusion predict venous thromboembolic
      events following radical prostatectomy with pelvic lymphadenectomy.
AB  - PURPOSE: Venous thromboembolic events are the most common nonoperative
      complication after radical prostatectomy and they represent the most common cause
      of death within 30 days of surgery. While effective mechanical and
      chemoprophylaxis exists, such prophylaxis may also be associated with increased
      complications. To identify venous thromboembolic event risk factors and, thereby,
      facilitate targeted prophylaxis we characterized clinicopathological variables
      associated with these events in patients undergoing radical prostatectomy.
      MATERIALS AND METHODS: We reviewed the records of 18,472 consecutive patients who
      underwent radical prostatectomy with pelvic lymphadenectomy for prostate cancer
      at our institution from 1987 to 2010. Patients were followed postoperatively for
      complications. Venous thromboembolic events within 30 days of surgery were
      recorded. Logistic regression models were used to analyze clinicopathological
      variables associated with venous thromboembolic events. RESULTS: We identified
      symptomatic venous thromboembolic events in 271 patients (1.4%). This diagnosis
      was not associated with preoperative body mass index, prostate specific antigen,
      Gleason score or cancer recurrence. However, the diagnosis was significantly
      associated with nonO blood type (OR 1.98, p = 0.004), an increasing number of
      lymph nodes removed (OR 1.05, p = 0.035) and blood transfusion (OR 1.30, p =
      0.02). Patients with venous thromboembolic events were significantly more likely
      to die within 30 days of surgery (3.0% vs 0%, p <0.001). CONCLUSIONS: Blood type,
      pelvic lymphadenectomy extent and blood transfusion are significant risk factors
      for symptomatic venous thromboembolic event before radical prostatectomy plus
      pelvic lymph node dissection. These data should be used for patient counseling,
      particularly in regard to obviating lymphadenectomy in patients at low risk and
      for individualizing prophylaxis for venous thromboembolic event in patients at
      higher risk.

PMID- 24140844
TI  - Laparoscopic pyeloplasty in children with horseshoe kidney.
AB  - PURPOSE: Laparoscopic pyeloplasty for ureteropelvic junction obstruction
      associated with horseshoe kidney has been described in adults but seldom in young
      children. We describe our experience in 10 children treated successfully with
      laparoscopic dismembered pyeloplasty. MATERIALS AND METHODS: Eight boys and 2
      girls with a mean age of 8 years (range 0.7 to 16.5) underwent laparoscopic
      dismembered pyeloplasty for ureteropelvic junction obstruction associated with
      horseshoe kidney between 2002 and 2012. Presenting symptoms were abdominal pain
      (3 patients), urinary tract infection (2), abdominal mass (1) and hematuria (1).
      Horseshoe kidney was diagnosed preoperatively in all cases but 1. The anastomosis
      was done by running or interrupted 5-zero or 6-zero resorbable sutures and
      drained by a Double-J(r) stent. RESULTS: Laparoscopic dismembered pyeloplasty was
      feasible in all cases. Mean operating time was 220 minutes (range 180 to 260).
      Anatomical abnormalities included anteriorly crossing vessels at the
      ureteropelvic junction in 6 cases (polar vessels in 4, ureteropelvic junction
      posterior to an abnormal branch of vena cava in 1 and renal vein in 1) and high
      ureteral insertion in 4. Two children underwent an extensive reduction
      pyeloplasty. Mean hospital stay was 3.2 days (range 1 to 8). Mean followup was 50
      months (range 4 to 132). All patients were asymptomatic with significant
      improvement of dilatation. CONCLUSIONS: The transperitoneal laparoscopic approach
      is adapted for pyeloplasty in children with horseshoe kidney. This procedure
      allows global exploration of the upper tract and efficient identification of
      anatomical anomalies, especially crossing vessels. Although our series is small,
      it is the first known description specific to horseshoe kidney in children and
      demonstrates that this approach has lasting effectiveness in young children.

PMID- 24140845
TI  - Dual energy computerized tomography with a split bolus-a 1-stop shop for patients
      with suspected urinary stones?
AB  - PURPOSE: We evaluated a dual energy, split bolus computerized tomography protocol
      that provides virtual noncontrast, parenchymal and urographic phases in a single
      scan. We assessed the sensitivity of the virtual noncontrast phase using this
      protocol to detect urinary stones compared to the gold standard of the true
      noncontrast phase. MATERIALS AND METHODS: We prospectively enrolled in the study
      81 patients who underwent unenhanced single energy computerized tomography at 120
      kV/200 mA as well as contrast enhanced dual energy computerized tomography on a
      Somatom(r) Definition Flash-CT (tube A 80 kV/233 mA and tube B SN 140 kV/180 mA
      with 1/0.8 mm slice thickness). For the split bolus protocol 400 mg/ml Iomeron(r)
      were injected at 2 time points, that is 15 ml 10 minutes before the scan and 80
      ml 65 seconds before the scan. In a consensus reading 2 readers evaluated the
      presence and diameter of stones on the true and virtual noncontrast phases.
      RESULTS: Of the 350 stones noted on the true noncontrast phase we found 289 on
      the virtual noncontrast phase as well as 13 false-positive and 66 false-negative
      stones. Sensitivity was 98.4%, 89.8% and 82.6% per patient, segment and stone,
      respectively. The diameter measured on the virtual noncontrast phase corresponded
      to a mean +/- SD 92.5% +/- 31.6% of the diameter on the true noncontrast phase.
      The mean effective dose was 4.8 +/- 1.8 and 10.5 +/- 3.7 mSv for the true and
      virtual noncontrast phases, respectively. CONCLUSIONS: The proposed protocol
      allows for combining 3 phases in a single scan while still enabling the detection
      of urinary stones at high sensitivity. This technique halves the radiation dose
      and provides the surgeon with better anatomical information on the calyceal
      system. Therefore, it is a valuable diagnostic tool for kidney stone treatment
      planning and followup.

PMID- 24140847
TI  - An assessment of PTV margin based on actual accumulated dose for prostate cancer
      radiotherapy.
AB  - The purpose of this work is to present the results of a margin reduction study
      involving dosimetric and radiobiologic assessment of cumulative dose
      distributions, computed using an image guided adaptive radiotherapy based
      framework. Eight prostate cancer patients, treated with 7-9, 6 MV, intensity
      modulated radiation therapy (IMRT) fields, were included in this study. The
      workflow consists of cone beam CT (CBCT) based localization, deformable image
      registration of the CBCT to simulation CT image datasets (SIM-CT), dose
      reconstruction and dose accumulation on the SIM-CT, and plan evaluation using
      radiobiological models. For each patient, three IMRT plans were generated with
      different margins applied to the CTV. The PTV margin for the original plan was 10
      mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was
      reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in
      predicted tumor control probability (TCP) in the accumulated (actual) plans in
      comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0%
      with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in
      predicted normal tissue complication probability (NTCP) for grades 2/3 rectal
      bleeding for the actual plans in comparison to the static plans with margins of
      10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual
      dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6%
      on average when the margin was reduced from 10/6 mm to 5/3 mm, and further
      reduced by 1.0% on average when the margin was reduced to 3 mm. The average
      reduction in complication free tumor control probability (P+) in the actual plans
      in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%,
      2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the
      actual plan with 3 mm margin came from one outlier, where individualizing patient
      treatment plans through margin adaptation based on biological models, might yield
      higher quality treatments. 

PMID- 24140846
TI  - Secondary data analysis of large data sets in urology: successes and errors to
      avoid.
AB  - PURPOSE: Secondary data analysis is the use of data collected for research by
      someone other than the investigator. In the last several years there has been a
      dramatic increase in the number of these studies being published in urological
      journals and presented at urological meetings, especially involving secondary
      data analysis of large administrative data sets. Along with this expansion,
      skepticism for secondary data analysis studies has increased for many urologists.
      MATERIALS AND METHODS: In this narrative review we discuss the types of large
      data sets that are commonly used for secondary data analysis in urology, and
      discuss the advantages and disadvantages of secondary data analysis. A literature
      search was performed to identify urological secondary data analysis studies
      published since 2008 using commonly used large data sets, and examples of high
      quality studies published in high impact journals are given. We outline an
      approach for performing a successful hypothesis or goal driven secondary data
      analysis study and highlight common errors to avoid. RESULTS: More than 350
      secondary data analysis studies using large data sets have been published on
      urological topics since 2008 with likely many more studies presented at meetings
      but never published. Nonhypothesis or goal driven studies have likely constituted
      some of these studies and have probably contributed to the increased skepticism
      of this type of research. However, many high quality, hypothesis driven studies
      addressing research questions that would have been difficult to conduct with
      other methods have been performed in the last few years. CONCLUSIONS: Secondary
      data analysis is a powerful tool that can address questions which could not be
      adequately studied by another method. Knowledge of the limitations of secondary
      data analysis and of the data sets used is critical for a successful study. There
      are also important errors to avoid when planning and performing a secondary data
      analysis study. Investigators and the urological community need to strive to use
      secondary data analysis of large data sets appropriately to produce high quality
      studies that hopefully lead to improved patient outcomes.

PMID- 24140848
TI  - Catalytic hydrothermal upgradation of wheat husk.
AB  - Catalytic hydrothermal upgradation of wheat husk was performed at 280 degrees C
      for 15 min in the presence of alkaline catalysts (KOH and K2CO3). The effect of
      alkaline catalysts on the yield of bio-oil products and composition of bio-oils
      obtained were discussed. Total bio-oil yield (31%) comprising of bio-oil1 (ether
      fraction) and bio-oil2 (acetone fraction) was maximum with K2CO3 solution. Powder
      XRD (X-ray diffraction) analysis of wheat husk as well as bio-residue samples
      show that the peaks due to cellulose, hemicellulose and lignin become weak in bio
      residue samples which suggest that these components have undergone hydrolytic
      cleavage/decomposition. The FTIR spectra of bio-oils indicate that the lignin in
      the wheat husk samples was decomposed to low molecular weight phenolic compounds.
      (1)H Nuclear Magnetic Resonance (NMR) spectrum of bio-oil1 shows more than 50% of
      the protons resonate in the up field region from 0.5 ppm to 3.0 ppm.

PMID- 24140849
TI  - Bioelectricity production from food waste leachate using microbial fuel cells:
      effect of NaCl and pH.
AB  - Microbial fuel cells are a promising technology for simultaneous treatment and
      energy recovery from food waste leachate. This study evaluates the effects of
      NaCl (0-150 mM) and pH on the treatment of food waste leachate using microbial
      fuel cells. The food waste leachate amended with 100mM NaCl enabled the highest
      maximum power density (1000 mW/m(3)) and lowest internal resistance (371Omega).
      Increasing the anodic pH gradually from acidic to alkaline conditions (pH 4-9)
      resulted in a gradual increase in maximum power density to 9956 mW/m(3) and
      decrease in internal cell resistance to 35.3Omega. The coulombic efficiency
      obtained under acidic conditions was only 17.8%, but increased significantly to
      60.0% and 63.4% in the neutral and alkaline pH's MFCs, respectively. Maintaining
      a narrow pH window (6.3-7.6) was essential for efficient bioelectricity
      production and COD removal using microbial fuel cells for the treatment of food
      waste leachate.

PMID- 24140850
TI  - Bioelectricity generation in continuously-fed microbial fuel cell: effects of
      anode electrode material and hydraulic retention time.
AB  - The main aim of this study is to investigate the bioelectricity production in
      continuously-fed dual chambered microbial fuel cell (MFC). Initially, MFC was
      operated with different anode electrode material at constant hydraulic retention
      time (HRT) of 2d to evaluate the effect of electrode material on electricity
      production. Pt electrode yielded about 642 mW/m(2) power density, which was 4
      times higher than that of the MFC with the mixed metal oxide titanium (Ti-TiO2).
      Further, MFC equipped with Pt electrode was operated at varying HRT (2-0.5d). The
      power density generation increased with decreasing HRT, corresponding to 1313
      mW/m(2) which was maximum value obtained during this study. Additionally,
      decreasing HRT from 2 to 0.5d resulted in increasing effluent dissolved organic
      carbon (DOC) concentration from 1.92 g/L to 2.23 g/L, corresponding to DOC
      removal efficiencies of 46% and 38%, respectively.

PMID- 24140851
TI  - Evaluation of humic fractions potential to produce bio-oil through catalytic
      hydroliquefaction.
AB  - Humic substances were extracted from biodegraded lignocellulosic biomass (LCBb)
      and submitted to catalytic hydroliquefaction. The resulting bio-oils were
      compared with those of the initial biomass. Compared to fulvic and humic acids,
      humin presented a high conversion rate (74 wt.%) and the highest amount of liquid
      fraction (66 wt.%). Moreover it represented 78% of LCBb. Humin produced 43 wt.%
      of crude oil and 33 wt.% of hexane soluble fraction containing hydrocarbons which
      is a higher yield than those from other humic substances as well as from the
      initial biomass. Hydrocarbons were mainly aromatics, but humin produces the
      highest amount of aliphatics. Considering the quantity, the quality and the
      molecular composition of the humic fractions, a classification of the potential
      of the latter to produce fuel using hydroliquefaction process can be assess:
      Hu>AF>AH. The higher heating value (HHV) and oxygen content of HSF from humin
      were fully compatible with biofuel characteristics.

PMID- 24140852
TI  - Impact of sweet sorghum cuticular waxes (SSCW) on acetone-butanol-ethanol
      fermentation using Clostridium acetobutylicum ABE1201.
AB  - The effect of cuticular waxes of sweet sorghum stem on acetone-butanol-ethanol
      (ABE) fermentation process was investigated. About 22.9% of butanol and 25.4% of
      ABE were decreased with fermentation period extended when SSCW was added. The
      inhibition of SSCW militate against both acidogenesis and solventogenesis phase,
      which were inconsistent with the inhibition of lignocellulose hydrolysate.
      Further studies on the composition of SSCW were performed. Regulations of
      inhibition with different carbon chain length of main compositions of SSCW on ABE
      fermentation were also investigated.

PMID- 24140853
TI  - Start-up of the SHARON and ANAMMOX process in landfill bioreactors using aerobic
      and anaerobic ammonium oxidising biomass.
AB  - The main aim of this study is to analyse the feasibility to use aerobic ammonium
      oxidising bacteria (AOB) and anammox/AnAOB biomass enriched from mined municipal
      solid waste for in situ SHARON and ANAMMOX processes in laboratory scale landfill
      bioreactors (LFBR) for ammonia nitrogen removal. For this purpose, three LFBRs
      were operated as Control (without biomass seed), SHARON (with AOB biomass seed)
      and ANAMMOX (with anammox biomass seed) for 315 days. Results showed nitrogen
      loading rate of 1.0 kg N/d was effectively removed in SHARON and ANAMMOX LFBR. In
      SHARON LFBR, partial nitritation efficiency reached up to 98.5% with AOB
      population of MPN of 5.1 * 10(6)/mL obtained. ANAMMOX LFBR gave evolution of 95%
      of nitrogen gas as the end product confirmed the ANAMMOX process. Nitrogen
      transformations, biomass development and hydrazine and hydroxylamine formation
      authenticated the enriched AOB and anammox biomass activity in landfill
      bioreactors.

PMID- 24140854
TI  - The study of organic removal efficiency and halophilic bacterial mixed liquor
      characteristics in a membrane bioreactor treating hypersaline produced water at
      varying organic loading rates.
AB  - In this study the organic pollutant removal performance and the mixed liquor
      characteristics of a membrane bioreactor (MBR), employing a halophilic bacterial
      consortium, for the treatment of hypersaline synthetic produced water - at
      varying organic loading rates (OLR) from 0.3 to 2.6 kg CODm(-3)d(-1) - were
      considered. The oil and grease (O&G) and COD removal efficiency were 95-99% and
      83-93%, respectively with only transient O&G (mainly polycyclic aromatic
      hydrocarbons) and soluble microbial products accumulation being observed. With
      increasing OLR, in the range 0.9-2.6 kg COD m(-3)d(-1), as a result of change in
      both extracellular polymeric substances (EPS) and zeta potential, bioflocculating
      ability improved but the compressibility of the flocs decreased resulting in the
      occurrence of EPS bulking at the highest OLR studied. The latter resulted in a
      change in the rheology of the mixed liquor from Newtonian to non-Newtonian and
      the occurrence of significant membrane fouling.

PMID- 24140855
TI  - Synergistic effect of rice husk addition on hydrothermal treatment of sewage
      sludge: fate and environmental risk of heavy metals.
AB  - Hydrothermal treatment (HTT) at 200 degrees C was applied to immobilize heavy
      metals (HMs) and the effect of rice husk (RH) addition was investigated based on
      total HMs concentration, fractionation and leaching tests. The results indicated
      that a synergistic effect of RH addition and HTT could be achieved on reducing
      the risk of HMs from medium and low risk to no risk. Metals were redistributed
      and transformed from weakly bounded state to stable state during the HTT process
      under RH addition. Notably at a RH/sludge ratio of 1/1.75 (d.w.), all the HMs
      showed no eco-toxicity and no leaching toxicity, with the concentrations of
      leachable Cr, Ni, Cu and Cd decreased by 17%, 89%, 95% and 93%, respectively.
      This synergistic effect of RH addition and HTT on the risk reduction of HMs
      implies that HTT process with RH addition could be a promising and safe disposal
      technology for sewage sludge treatment in practice. 

PMID- 24140856
TI  - Quinone-mediated microbial synthesis of reduced graphene oxide with peroxidase
      like activity.
AB  - The effects of different quinones on graphene oxide (GO) reduction by Shewanella
      oneidensis MR-1 and the peroxidase activity of the resultant reduced graphene
      oxide (QRGO) were studied. The presence of 100 MUM anthraquinone-2-sulfonate
      (AQS), anthraquinone-2,6-disulfonate and 5-hydroxy-1,4-naphthoquinone could lead
      to 1.6-2.8-fold increase in GO reduction rate, whereas anthraquinone-2
      carboxylate slowed down the reduction. The stimulating effects of AQS increased
      with the increase of its concentration (10-100 MUM). The mediated effects were
      proved by direct GO reduction by microbially reduced AQS. The mediated reduction
      of GO to QRGO was characterized by UV-vis, XRD, FTIR, Raman spectra, XPS, TEM and
      AFM, respectively. The as-prepared QRGO possessed peroxidase-like activity, which
      could catalyze the oxidation of 3,3'5,5'-tetramethylbenzidine by H2O2, and
      followed Michealis-Menten kinetics. A colorimetric sensor for quantitative
      determination of glucose based on the peroxidase activity of QRGO was developed
      over a range of 1-120 MUM with a detection limit of 1 MUM.

PMID- 24140857
TI  - Hydrothermal liquefaction of Litsea cubeba seed to produce bio-oils.
AB  - Hydrothermal liquefaction (HTL) of Litsea cubeba seed was conducted over
      different temperature (250-350 degrees C), time (30-120 min), reactor loading
      (0.5-4.5 g) and Na2CO3 loading (0-10 wt.%). Temperature was the most influential
      factor affecting the yields of product fractions. The highest bio-oil yield of
      56.9 wt.% was achieved at 290 degrees C, 60 min, and reactor loading of 2.5 g.
      The presence of Na2CO3 favored the conversion of the feedstock but suppressed the
      production of bio-oil. The higher heating values of the bio-oil were estimated at
      around 40.8 MJ/kg. The bio-oil, which mainly consisted of toluene, 1-methyl-2-(1
      methylethyl)-benzene, fatty acids, fatty acid amides, and fatty acid esters, had
      a smaller total acid number than that of the oil obtained from the direct
      extraction of the starting material. It also contained nitrogen that was far
      below the bio-oil produced from the HTL of microalgae, making it more suitable
      for the subsequent refining.

PMID- 24140858
TI  - Geochemical controls on fluoriferous groundwaters of the Pliocene and the more
      recent aquifers: the case of Aigion region, Greece.
AB  - High fluoride concentrations (>8 mg/L) in the groundwater of the Plio-Pleistocene
      sediments are rare; however, this is the case around Aigion town, where teeth
      fluorosis has been detected since the 80s. Aiming to investigate the origin and
      the mobility mechanism of fluorine in groundwater and sediments a hydrogeological
      and geochemical research has been conducted. The hydrogeological research
      revealed that the Na-HCO3 water type of boreholes aligned along a fault and
      hosted in the confined aquifers display the higher fluoride content. The
      unconfined aquifer is mostly dominated by Na-Ca-Mg-HCO3-SO4 water, which displays
      much lower fluoride concentrations. The most permeable sectors of this aquifer
      host fresh water of Ca-HCO3 type. The geochemical research revealed significant
      amount of fluorine in the base of a lignite sequence hosted in the Plio
      Pleistocene sediments. The Na-HCO3 water type represents a deep water
      circulation, proved by its elevated temperature and isotopic composition,
      carrying a significant load of fluorine and trace elements. During its uprise
      through faults and the Plio-Pleistocene sediments, part of its load is being
      deposited on the base of the lignite beds. Leaching experiments and mineralogical
      determinations in lignite samples revealed enrichment in fluorine at the bottom
      of the studied lignite sequence, where silicate minerals are dominant. This is
      due to either, the presence of F-bearing minerals or the presence of organic
      matter which can also absorb/adsorb fluorine. At the upper part of the sequence,
      where carbonates prevail, calcite is the major phase indicating the circulation
      of Ca-EtaCO3-rich fresh water. The Na-Ca-Mg-HCO3-SO4 water type could be
      considered as mixed water spending longer time in sediments of relatively low
      permeability and thus, dissolving fluorine and trace elements from clay minerals
      and organic matter.

PMID- 24140859
TI  - Empirical potential structure refinement of semi-crystalline polymer systems:
      polytetrafluoroethylene and polychlorotrifluoroethylene.
AB  - Empirical potential structure refinement (EPSR) simulations are performed on
      total neutron scattering data from powder samples of polytetrafluoroethylene
      (PTFE) and polychlorotrifluoroethylene (PCTFE), both at 300 K. Starting from
      single strands of polymer consisting of between 30 and 60 monomers of
      tetrafluoroethylene and chlorotrifluoroethylene in each case, hexagonal
      simulation cells are constructed consisting of an array 25 (5*5) such strands
      placed on a hexagonal lattice. Allowed simulation moves are polymer translation
      moves along all three Cartesian axes, whole polymer rotations about the polymer
      axis, and individual atom moves within each polymer. For PTFE a number of Bragg
      peaks are visible in the scattering data and these are found to be consistent
      with a lattice spacing a(=b) = 5.69(1) A with a dihedral angle along the
      (helical) chain of 166 degrees  which gives a repeat distance along the chain (c
      axis) of ~19.6 A. The positions of the Bragg peaks are well reproduced by this
      model, although there is a mismatch in the amplitudes of some of the higher order
      reflections between simulation and data. For PCTFE there is only one visible
      Bragg peak (100) which is well reproduced by a hexagonal lattice of atactic
      parallel polymers with a spacing of a(=b) = 6.37(1) A. In this case the absence
      of distinct reflections along the polymer c-axis makes characterization of the
      internal dihedral angle difficult, but a model with a dihedral angle of 166
      degrees  was less successful at fitting the diffuse scattering than a model where
      this angle was set to 180 degrees , giving a nearly straight trans (zig-zag)
      structure. For PCTFE little change in structure could be discerned when the
      material was heated to 550 K, apart from a slight increase in lattice spacing. In
      both cases there is substantial diffuse scattering between the Bragg peaks, and
      this is correctly replicated by the EPSR simulations.

PMID- 24140860
TI  - Differential regulation of human cathelicidin LL-37 by free fatty acids and their
      analogs.
AB  - LL-37 is the single cathelicidin host defense peptide in humans with direct
      antimicrobial and immunomodulatory activities. Specific regulation of LL-37
      synthesis has emerged as a novel non-antibiotic approach to disease control and
      prevention. Short-chain fatty acids, and butyrate in particular, were found
      recently to be strong inducers of LL-37 gene expression without causing
      inflammation. Here, we further evaluated the LL-37-inducing efficiency of a broad
      range of saturated free fatty acids and their derivatives in human HT-29 colonic
      epithelial cells and U-937 monocytic cells by real-time RT-PCR. Surprisingly, we
      revealed that valerate, hexanoate, and heptanoate with 5-7 carbons are more
      potent than 4-carbon butyrate in promoting LL-37 gene expression in both cell
      types. Free fatty acids with longer than 7 or shorter than 4 carbons showed only
      a marginal effect on LL-37 expression. Studies with a series of fatty acid
      derivatives with modifications in the aliphatic chain or carboxylic acid group
      yielded several analogs such as benzyl butyrate, trans-cinnamyl butyrate,
      glyceryl tributyrate, and phenethyl butyrate with a comparable LL-37-inducing
      activity to sodium butyrate. On the other hand, although reactive, the anhydride
      derivatives of short- and medium-chain fatty acids are as potent as their
      corresponding free acid forms in LL-37 induction. Thus, these newly identified
      free fatty acids and their analogs with a strong capacity to augment LL-37
      synthesis may hold promise as immune boosting dietary supplements for
      antimicrobial therapy. 

PMID- 24140861
TI  - Understanding the pelvic anatomy.
AB  - The pelvic anatomy is constant, with few variations. It has a distinct appearance
      when observed using the 2-dimensional laparoscope. Thus it is important to master
      the laparoscopic anatomy and use this knowledge to perform better surgery. The
      laparoscope offers better vision in a narrow space and thus helps better
      understanding of the anatomy than what can be seen during open surgery. The
      objectives of this video are to enable the observer to become familiar with the
      surgical anatomy, to apply anatomical knowledge to develop fine surgical skills,
      and to address the myths of open surgical anatomy. The lucid graphics, images,
      and commentary will enable easy understanding of the pelvic anatomy. 

PMID- 24140863
TI  - The role of thioredoxin-1 in suppression of endoplasmic reticulum stress in
      Parkinson disease.
AB  - Endoplasmic reticulum (ER) stress has been implicated in Parkinson disease. We
      previously reported that thioredoxin 1 (Trx-1) suppressed the ER stress caused by
      1-methy-4-phenyl-1,2,3,6-tetrahydropyridine; however, its molecular mechanism
      remains largely unknown. In the present study, we showed that 1-methyl-4
      phenylpyridinium ion (MPP(+)) induced ER stress by activating glucose-regulated
      protein 78 (GRP78), inositol-requiring enzyme 1alpha (IRE1alpha), tumor necrosis
      factor receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinase (JNK),
      caspase-12, and C/EBP homologous protein (CHOP) in PC12 cells. The downregulation
      of Trx-1 aggravated the ER stress and further increased the expression of the
      above molecules induced by MPP(+). In contrast, overexpression of Trx-1
      attenuated the ER stress and repressed the expression of the above molecules
      induced by MPP(+). More importantly, the overexpression of Trx-1 in transgenic
      mice suppressed ER stress by inhibiting the activation of these molecules. We
      present, for the first time, the molecular mechanism of Trx-1 suppression of
      endoplasmic reticulum stress in Parkinson disease in vitro and in vivo. Based on
      our findings, we conclude that Trx-1 plays a neuroprotective role in Parkinson
      disease by suppressing ER stress by regulating the activation of GRP78,
      IRE1alpha, TRAF2, JNK, caspase-12, and CHOP. 

PMID- 24140862
TI  - Contribution of endogenously produced reactive oxygen species to the activation
      of podocyte NLRP3 inflammasomes in hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (hHcys) is an important pathogenic factor contributing to
      the progression of end-stage renal disease. Recent studies have demonstrated the
      implication of nicotinamide adenine dinucleotide phosphate oxidase-mediated NLRP3
      inflammasome activation in the development of podocyte injury and glomerular
      sclerosis during hHcys. However, it remains unknown which reactive oxygen species
      (ROS) are responsible for this activation of NLRP3 inflammasomes and how such
      action of ROS is controlled. This study tested the contribution of common
      endogenous ROS including superoxide (O2(-)), hydrogen peroxide (H2O2),
      peroxynitrite (ONOO(-)), and hydroxyl radical (OH) to the activation of NLRP3
      inflammasomes in mouse podocytes and glomeruli. In vitro, confocal microscopy and
      size-exclusion chromatography demonstrated that dismutation of O2(-) by 4-hydroxy
      2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) and decomposition of H2O2 by
      catalase prevented Hcys-induced aggregation of NLRP3 inflammasome proteins and
      inhibited Hcys-induced caspase-1 activation and IL-1beta production in mouse
      podocytes. However, scavenging of ONOO(-) or OH had no significant effect on
      either Hcys-induced NLRP3 inflammasome formation or activation. In vivo,
      scavenging of O2(-) by Tempol and removal of H2O2 by catalase substantially
      inhibited NLRP3 inflammasome formation and activation in glomeruli of hHcys mice
      as shown by reduced colocalization of NLRP3 with ASC or caspase-1 and inhibition
      of caspase-1 activation and IL-1beta production. Furthermore, Tempol and catalase
      significantly attenuated hHcys-induced glomerular injury. In conclusion,
      endogenously produced O2(-) and H2O2 primarily contribute to NLRP3 inflammasome
      formation and activation in mouse glomeruli resulting in glomerular injury or
      consequent sclerosis during hHcys. 

PMID- 24140864
TI  - Alcohol induces mitochondrial redox imbalance in alveolar macrophages.
AB  - Alcohol abuse suppresses the immune responses of alveolar macrophages (AMs) and
      increases the risk of a respiratory infection via chronic oxidative stress and
      depletion of critical antioxidants within alveolar cells and the alveolar lining
      fluid. Although alcohol-induced mitochondrial oxidative stress has been
      demonstrated, the oxidation of the mitochondrial thioredoxin redox circuit in
      response to alcohol has not been examined. In vitro ethanol exposure of a mouse
      AM cell line and AMs from ethanol-fed mice demonstrated NADPH depletion
      concomitant with oxidation of mitochondrial glutathione and oxidation of the
      thioredoxin redox circuit system including thioredoxin 2 (Trx2) and thioredoxin 2
      reductase (Trx2R). Mitochondrial peroxiredoxins (Prdx's), which are critical for
      the reduction of the thioredoxin circuit, were irreversibly hyperoxidized to an
      inactive form. Ethanol also decreased the mRNAs for Trx2, Trx2R, Prdx3, and Prdx5
      plus the mitochondrial thiol-disulfide proteins glutaredoxin 2, glutathione
      reductase, and glutathione peroxidase 2. Thus, the mitochondrial thioredoxin
      circuit was highly oxidized by ethanol, thereby compromising the mitochondrial
      antioxidant capacity and ability to detoxify mitochondrial reactive oxygen
      species. Oxidation of the mitochondrial thioredoxin redox circuit would further
      compromise the transient oxidation of thiol groups within specific proteins, the
      basis of redox signaling, and the processes by which cells respond to oxidants.
      Impaired mitochondria can then jeopardize cellular function of AMs, such as
      phagocytosis, which may explain the increased risk of respiratory infection in
      subjects with an alcohol use disorder. 

PMID- 24140865
TI  - Metabolic syndrome-induced tubulointerstitial injury: role of oxidative stress
      and preventive effects of acetaminophen.
AB  - The prevalence of metabolic syndrome persistently increases and affects over 30%
      of U.S. adults. To study how metabolic syndrome may induce tubulointerstitial
      injury and whether acetaminophen has renal-protective properties, 4-week-old
      obese Zucker rats were randomly assigned into three groups, control (OC), vehicle
      dimethyl sulfoxide (OV), and acetaminophen treatment (30 mg/kg/day for 26 weeks),
      and lean Zucker rats served as healthy controls. Significant tubulointerstitial
      injuries were observed in both OC and OV animals, evidenced by increased tubular
      cell death, tubular atrophy/dilation, inflammatory cell infiltration, and
      fibrosis. These tubulointerstitial alterations were significantly reduced by
      treatment with a chronic but low dose of acetaminophen, which acted to diminish
      NADPH oxidase isoforms Nox2 and Nox4 and decrease tubulointerstitial oxidative
      stress (reduced tissue superoxide and macromolecular oxidation). Decreased
      oxidative stress by acetaminophen was paralleled by the reduction of tubular
      proapoptotic signaling (diminished Bax/Bcl-2 ratio and caspase 3 activation) and
      the alleviation of tubular epithelial-to-mesenchymal transition (decreased
      transforming growth factor beta, connective tissue growth factor, alpha-smooth
      muscle actin, and laminin). These data suggest that increased oxidative stress
      plays a critical role in mediating metabolic syndrome-induced tubulointerstitial
      injury and provide the first evidence suggesting that acetaminophen may be of
      therapeutic benefit for the prevention of tubulointerstitial injury.

PMID- 24140867
TI  - Cholera toxin breakdowns oral tolerance via activation of canonical NF-kappaB.
AB  - The mechanisms of mucosal immunogenicity and adjuvanticity of bacterial exotoxins
      remains unknown. In this study, we investigated the role of the transcription
      factor nuclear factor-kappaB (NF-kappaB) in cholera toxin (CT)-induced alteration
      of oral tolerance. Feeding CT abrogated ovalbumin (OVA)-induced oral tolerance,
      as evaluated by OVA-specific serum antibody responses, and CD4(+) T cell
      proliferation. CT feeding activated canonical NF-kappaB (one heterodimer type,
      p50-p65) and mRNA expression of NF-kappaB-dependent proinflammatory cytokines in
      mesenteric lymph node (MLN) and Peyer's patch (PP) cells. CT no longer showed
      abrogation of oral tolerance in mice pretreated with p50 small interfering RNAs
      (siRNAs). ADP-ribosylation inhibitors inhibited CT-induced NF-kappaB activation.
      These data suggest that CT induces canonical NF-kappaB activation in intestinal
      lymphoid cells, which plays a key role in mucosal immunogenicity and
      adjuvanticity.

PMID- 24140866
TI  - Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage
      and increases survival during 1918 influenza virus infection in mice.
AB  - The 1918 influenza pandemic caused over 40 million deaths worldwide, with 675,000
      deaths in the United States alone. Studies in several experimental animal models
      showed that 1918 influenza virus infection resulted in severe lung pathology
      associated with dysregulated immune and cell death responses. To determine if
      reactive oxygen species produced by host inflammatory responses play a central
      role in promoting severity of lung pathology, we treated 1918 influenza virus
      infected mice with the catalytic catalase/superoxide dismutase mimetic, salen
      manganese complex EUK-207 beginning 3 days postinfection. Postexposure treatment
      of mice infected with a lethal dose of the 1918 influenza virus with EUK-207
      resulted in significantly increased survival and reduced lung pathology without a
      reduction in viral titers. In vitro studies also showed that EUK-207 treatment
      did not affect 1918 influenza viral replication. Immunohistochemical analysis
      showed a reduction in the detection of the apoptosis marker cleaved caspase-3 and
      the oxidative stress marker 8-oxo-2'-deoxyguanosine in lungs of EUK-207-treated
      animals compared to vehicle controls. High-throughput sequencing and RNA
      expression microarray analysis revealed that treatment resulted in decreased
      expression of inflammatory response genes and increased lung metabolic and repair
      responses. These results directly demonstrate that 1918 influenza virus infection
      leads to an immunopathogenic immune response with excessive inflammatory and cell
      death responses that can be limited by treatment with the catalytic antioxidant
      EUK-207. 

PMID- 24140868
TI  - Inhibition of phosphate transporters ameliorates the inflammatory and necrotic
      side effects of the nitrogen-containing bisphosphonate zoledronate in mice.
AB  - Bisphosphonates (BPs) are pyrophosphate analogs. They are widely used against
      enhanced bone-resorption in various diseases. Nitrogen-containing BPs (N-BPs)
      exhibit strong anti-bone-resorptive effects but have inflammatory and necrotic
      side effects. The non-nitrogen-containing BPs (non-N-BPs) etidronate and
      clodronate lack such side effects, but their anti-bone-resorptive effects are
      weak. In mice, etidronate and clodronate reduce the inflammatory/necrotic effects
      of N-BPs, even those of zoledronate, the N-BP with the strongest anti-bone
      resorptive effect yet reported and the highest risk of inflammation/necrosis.
      Here, to explore the mechanisms underlying this protection, we used a mouse model
      in which a single reagent or a mixture of two reagents was injected
      subcutaneously into ear-pinnas. These reagents included zoledronate, four non-N
      BPs, pyrophosphate, and inhibitors of various organic-anion-transporters.
      Pyrophosphate and two of the four non-N-BPs (not etidronate or clodronate) had
      inflammatory/necrotic effects. These effects were reduced by etidronate and
      clodronate, but not by phosphonoformate, an inhibitor of two of the three known
      phosphate-transporter families. Phosphonoformate reduced the
      inflammatory/necrotic effects of zoledronate, but not those of pyrophosphate or
      of non-N-BPs. Conversely, pyrophosphate, at non-inflammatory/necrotic
      concentrations, reduced the inflammatory/necrotic effects of non-N-BPs, but not
      those of zoledronate. The efficacies of the protective effects against the
      inflammatory/necrotic effects of zoledronate were clodronate > etidronate >
      phosphonoformate. These findings suggest that (i) the N-BP zoledronate may enter
      soft-tissue cells via phosphonoformate-inhibitable phosphate-transporters, (ii)
      other phosphate-transporters may carry pyrophosphate and inflammatory/necrotic
      non-N-BPs into such cells, and (iii) etidronate and clodronate inhibit all these
      transporters, and they ameliorate the side effects of zoledronate by inhibiting
      phosphonoformate-inhibitable phosphate-transporters. 

PMID- 24140869
TI  - Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10
      deficiency.
AB  - Human COQ6 encodes a monooxygenase which is responsible for the C5-hydroxylation
      of the quinone ring of coenzyme Q (CoQ). Mutations in COQ6 cause primary CoQ
      deficiency, a condition responsive to oral CoQ10 supplementation. Treatment is
      however still problematic given the poor bioavailability of CoQ10. We employed S.
      cerevisiae lacking the orthologous gene to characterize the two different human
      COQ6 isoforms and the mutations found in patients. COQ6 isoform a can partially
      complement the defective yeast, while isoform b, which lacks part of the FAD
      binding domain, is inactive but partially stable, and could have a
      regulatory/inhibitory function in CoQ10 biosynthesis. Most mutations identified
      in patients, including the frameshift Q461fs478X mutation, retain residual
      enzymatic activity, and all patients carry at least one hypomorphic allele,
      confirming that the complete block of CoQ biosynthesis is lethal. These mutants
      are also partially stable and allow the assembly of the CoQ biosynthetic complex.
      In fact treatment with two hydroxylated analogues of 4-hydroxybenzoic acid,
      namely, vanillic acid or 3-4-hydroxybenzoic acid, restored the respiratory growth
      of yeast Deltacoq6 cells expressing the mutant huCOQ6-isoa proteins. These
      compounds, and particularly vanillic acid, could therefore represent an
      interesting therapeutic option for COQ6 patients. 

PMID- 24140870
TI  - Target-induced self-assembly of DNA nanomachine on magnetic particle for multi
      amplified biosensing of nucleic acid, protein, and cancer cell.
AB  - A biosensing system is established for the multi-amplified detection of DNA or
      specific substrates of aptamers under isothermal conditions, which combines
      nicked rolling circle amplification (N-RCA) and beacon assisted amplification
      (BAA) with sensitive colorimetric technique by using DNAzymes as reporter units.
      According to the configuration, the analysis of DNA is accomplished by
      recognizing the target to capture nucleic acid-functionalized magnetic particles,
      followed by the self-assembly of the other two nucleic acids into multicomponent
      DNA supramolecular structure on magnetic particles. After magnetic separation,
      the circularization with ligase and the fragmentation with polymerase activate N
      RCA and BAA in the presence of polymerase, dNTPs, and the nicking endonuclease,
      successively producing horseradish peroxidase (HRP)-mimicking DNAzymes that act
      as colorimetric reporter to catalyze the oxidation of ABTS(2-) by H2O2 in the
      presence of hemin. Under the optimized conditions, we obtain a wide dynamic range
      for DNA analysis over 6 orders of magnitude from 1.0 * 10(-14) to 1.0 * 10(-9)M
      with a low limit of detection of 6.8 * 10(-15)M. In the absence of a target,
      neither self-assembly of nucleic acids nor amplification process can be
      initiated, indicating an excellent selectivity of the proposed strategy.
      Similarly, an analogous system is activated by cancer cells or lysozyme through
      cooperative self-assembly of nucleic acids on magnetic particles in the presence
      of respective substrates of aptamers to synthesize HRP-mimicking DNAzymes that
      give the readout signal for the recognition events, achieving LODs of 81 Ramos
      cells and 7.2 * 10(-15)M lysozyme, respectively.

PMID- 24140871
TI  - E-assay concept: detection of bisphenol A with a label-free electrochemical
      competitive immunoassay.
AB  - A label-free electrochemical immunosensor was developed by electropolymerization
      of N-(3-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)propyl) 3-(5-hydroxy-1,4
      dihydro-1,4-dioxonaphthalen-2(3)-yl)propionamide (JugBPA). By combination with an
      antibody directed to bisphenol A (alphaBPA), this conducting polymer-based
      biosensor can detect BPA directly with a limit of detection of 2pgmL(-1). Square
      wave voltammetry shows that the polymer film presents a current decrease upon
      anti-BPA binding and an opposite current increase upon BPA addition in solution.
      This electrochemical immunosensor (E-assay) also shows high selectivity towards
      closely related compounds (bisphenol A dimethacrylate, and dibutyl phthalate).
      The E-assay concept described here could be a promising tool for simple, low-cost
      and reagentless on-site environmental monitoring.

PMID- 24140872
TI  - Novel graphene flowers modified carbon fibers for simultaneous determination of
      ascorbic acid, dopamine and uric acid.
AB  - A novel and sensitive carbon fiber electrode (CFE) modified by graphene flowers
      was prepared and used to simultaneously determine ascorbic acid (AA), dopamine
      (DA) and uric acid (UA). SEM images showed that beautiful and layer-petal
      graphene flowers homogeneously bloomed on the surface of CFE. Moreover, sharp and
      obvious oxidation peaks were found at the obtained electrode when compared with
      CFE and glassy carbon electrode (GCE) for the oxidation of AA, DA and UA. Also,
      the linear calibration plots for AA, DA and UA were observed, respectively, in
      the ranges of 45.4-1489.23 MUM, 0.7-45.21 MUM and 3.78-183.87 MUM in the
      individual detection of each component. By simultaneously changing the
      concentrations of AA, DA and UA, their oxidation peaks appeared at -0.05 V, 0.16
      V and 2.6 V, and the good linear responses ranges were 73.52-2305.53 MUM, 1.36
      125.69 MUM and 3.98-371.49 MUM, respectively. In addition, the obtained electrode
      showed satisfactory results when applied to the determination of AA, DA and UA in
      urine and serum samples.

PMID- 24140873
TI  - Polymer-coated fluorescent CdSe-based quantum dots for application in
      immunoassay.
AB  - The paper describes all stages of synthesis and characterization of biocompatible
      CdSe-based core/shell quantum dots (QDs) and their application as fluorescent
      label for immunoassay. Special attention was focused on development of maleic
      anhydride-based amphiphilic polymers for QDs solubilization in aqueous media. In
      this work two PEG-amines were tried for polymer modification: monoamine Jeffamine
      M 1000 used previously in some researches and diamine Jeffamine ED-2003 applied
      for the first time for QDs solubilization. The use of different Jeffamines allows
      us to obtain QDs with carboxyl or amine functional groups available for
      conjugation. The influence of polymer composition on optical properties of the
      nanocrystals and their stability in aqueous solutions as well as on their
      conjugation with biomolecules was studied. QDs with different coatings were used
      as biolabels in quantitative fluorescence microtiter plate immunoassay and
      qualitative on-site column test. It was found that quantum dots covered with
      amphiphilic polymer prepared from poly(maleic anhydride-alt-1-octadecene) and
      Jeffamine ED-2003 retained up to 90% of their initial brightness, easily
      conjugated with protein and showed low non-specific adsorption. In optimized
      conditions the obtained QDs were successfully used for determination of mycotoxin
      deoxynivalenol in wheat and maize samples by fluorescence microtiter plate
      immunoassay with an IC50 of 220 MUg kg(-1) and by on-site column test with cut
      off of 500 MUg kg(-1).

PMID- 24140874
TI  - Enhancing dissemination in selective eating disorders prevention: an
      investigation of voluntary participation among female university students.
AB  - Maximising dissemination of efficacious psychological interventions is an
      important undertaking, particularly in prevention work where the target
      population may not be seeking help. Consequently, the current study investigated
      voluntary participation in a selective eating disorder prevention programme by
      examining predictors of, and evaluating a motivational enhancement approach to,
      increased participation. Female students studying first-year psychology (N = 124,
      M(age) = 19.30, SD = 1.55) completed baseline measures, were randomised to a
      motivational or control condition, then presented with a flyer for an eating
      disorders prevention trial and assessed regarding potential participation.
      Results showed that interest and likelihood of participation were low overall and
      lack of time the most commonly endorsed reason. Participants high on weight
      concerns were more likely to cite the group format of the intervention as a
      deterrent. A greater belief in the helpfulness of body image programmes and
      higher personal ineffectiveness were significant predictors of interest in
      participation. There was no significant difference between those who did and did
      not undergo the motivational enhancement with respect to interest and likelihood
      of participation. These findings suggest important avenues for consideration when
      designing eating disorder prevention efforts relying on voluntary participation,
      and highlight the importance of evaluating programmes cross-culturally.

PMID- 24140875
TI  - Computation of induced electric field for the sacral nerve activation.
AB  - The induced electric field/current in the sacral nerve by stimulation devices for
      the treatment of bladder overactivity is investigated. Implanted and
      transcutaneous electrode configurations are considered. The electric field
      induced in the sacral nerve by the implanted electrode is largely affected by its
      surrounding tissues, which is attributable to the variation in the input
      impedance of the electrode. In contrast, the electric field induced by the
      transcutaneous electrode is affected by the tissue conductivity and anatomical
      composition of the body. In addition, the electric field induced in the
      subcutaneous fat in close proximity of the electrode is comparable with the
      estimated threshold electric field for pain. These computational findings explain
      the clinically observed weakness and side effect of each configuration. For the
      transcutaneous stimulator, we suggest that the electrode contact area be
      increased to reduce the induced electric field in the subcutaneous fat. 

PMID- 24140876
TI  - Conformational analysis of bis(methylthio)methane and diethyl sulfide molecules
      in the liquid phase: reverse Monte Carlo studies using classical interatomic
      potential functions.
AB  - Series of flexible molecule reverse Monte Carlo calculations, using bonding and
      non-bonding interatomic potential functions (FMP-RMC), were performed starting
      from previous molecular dynamics results that had applied the OPLS-AA and EncadS
      force fields. During RMC modeling, the experimental x-ray total scattering
      structure factor was approached. The discrepancy between experimental and
      calculated structure factors, in comparison with the molecular dynamics results,
      decreased substantially in each case. The room temperature liquid structure of
      bis(methylthio)methane is excellently described by the FMP-RMC simulation that
      applied the EncadS force field parameters. The main conformer was found to be AG
      with 55.2%, followed by 37.2% of G(+)G(+) (G(-)G(-)) and 7.6% of AA; the
      stability of the G(+)G(+) (G(-)G(-)) conformer is most probably caused by the
      anomer effect. The liquid structure of diethyl sulfide can be best described by
      applying the OPLS-AA force field parameters during FMP-RMC simulation, although
      in this case the force field parameters were found to be not fully compatible
      with experimental data. Here, the two main conformers are AG (50.6%) and the AA
      (40%). In addition to findings on the actual real systems, a fairly detailed
      comparison between traditional and FMP-RMC methodology is provided. 

PMID- 24140877
TI  - Epidemic dynamics on semi-directed complex networks.
AB  - In this paper an SIS model for epidemic spreading on semi-directed networks is
      established, which can be used to examine and compare the impact of undirected
      and directed contacts on disease spread. The model is analyzed for the case of
      uncorrelated semi-directed networks, and the basic reproduction number R0 is
      obtained analytically. We verify that the R0 contains the outbreak threshold on
      undirected networks and directed networks as special cases. It is proved that if
      R0<1 then the disease-free equilibrium is globally asymptotically stable,
      otherwise the disease-free equilibrium is unstable and the unique endemic
      equilibrium exists, which is globally asymptotically stable. Finally the
      numerical simulations holds for these analytical results are given. 

PMID- 24140879
TI  - Measurements of alpha-gamma coincidences with an optimized dual-parameter
      multichannel system.
AB  - Measurements of alpha-gamma coincidences have usually been carried out using a
      single channel to detect alpha-particles of a given energy, and a multichannel
      analyser for the detection of the corresponding coincident gamma-rays. An alpha
      gamma coincidence chamber coupled to the electronic chain ending with a dual
      parameter multichannel analyser has been developed and optimized. This system
      simultaneously stores alpha-particle, gamma-ray, and alpha-gamma coincidence
      spectra, which allows a general analysis to be made of the degree of coincidence
      between each alpha-particle and each gamma-ray emission. With this technique, a
      two-dimensional spectrum was obtained and analysed using "contour graphics". An
      application to the study of the decay scheme of (241)Am is described. 

PMID- 24140880
TI  - Environmental effects and characterization of the Egyptian radioactive well
      logging calibration pad facility.
AB  - A set of ten radioactive well-logging calibration pads were constructed in one of
      the premises of the Nuclear Materials Authority (NMA), Egypt, at 6th October
      city. These pads were built for calibrating geophysical well-logging instruments.
      This calibration facility was conducted through technical assistance and
      practical support of the International Atomic Energy Agency (IAEA) and (ARCN).
      There are five uranium pads with three different uranium concentrations and
      borehole diameters. The other five calibration pads include one from each of the
      following: blank, potassium, thorium, multi layers and mixed. More than 22 t of
      various selected Egyptian raw materials were gathered for pad construction from
      different locations in Egypt. Pad's site and the surrounding area were
      spectrometrically surveyed before excavation for the construction process of pad
      basin floor. They yielded negligible radiation values which are very near to the
      detected general background. After pad's construction, spectrometric measurements
      were carried out again in the same locations when the exposed bore holes of the
      pads were closed. No radioactivity leakage was noticed from the pads. Meanwhile,
      dose rate values were found to range from 0.12 to 1.26 mS/y. They were measured
      during the opening of bore holes of the pads. These values depend mainly upon the
      type and concentration of the pads as well as their borehole diameters. The
      results of radiospectrometric survey illustrate that the specification of top
      layers of the pads were constructed according to international standards.

PMID- 24140878
TI  - Translational strategies for therapeutic development in nicotine addiction:
      rethinking the conventional bench to bedside approach.
AB  - Tobacco produces an impressive burden of disease resulting in premature death in
      half of users. Despite effective smoking cessation medications (nicotine
      replacement therapies, bupropion and varenicline), there is a very high rate of
      relapse following quit attempts. The use of efficient strategies for the
      development of novel treatments is a necessity. A 'bench to bedside strategy' was
      initially used to develop cannabinoid CB1 receptor antagonists for the treatment
      of nicotine addiction. Unfortunately, after being tested on experimental animals,
      what seemed to be an interesting approach for the treatment of nicotine addiction
      resulted in serious unwanted side effects when tested in humans. Current research
      is focusing again on pre-clinical models in an effort to eliminate unwanted side
      effects while preserving the initially observed efficacy. A 'bed side to bench
      strategy' was used to study the role of the insula (part of the frontal cortex)
      in nicotine addiction. This line of research started based on clinical
      observations that patients suffering stroke-induced lesions to the insula showed
      a greater likelihood to report immediate smoking cessation without craving or
      relapse. Subsequently, animal models of addiction are used to explore the role of
      insula in addiction. Due to the inherent limitations existing in clinical versus
      preclinical studies, the possibility of close interaction between both models
      seems to be critical for the successful development of novel therapeutic
      strategies for nicotine dependence. 

PMID- 24140881
TI  - SPINVERT: a program for refinement of paramagnetic diffuse scattering data.
AB  - We present a program (spinvert; http://spinvert.chem.ox.ac.uk) for refinement of
      magnetic diffuse scattering data for frustrated magnets, spin liquids, spin
      glasses, and other magnetically disordered materials. The approach uses reverse
      Monte Carlo refinement to fit a large configuration of spins to experimental
      powder neutron diffraction data. Despite fitting to spherically averaged data,
      this approach allows the recovery of the three-dimensional magnetic diffuse
      scattering pattern and the spin-pair correlation function. We illustrate the use
      of the spinvert program with two case studies. First, we use simulated powder
      data for the canonical antiferromagnetic Heisenberg model on the kagome lattice
      to discuss the sensitivity of spinvert refinement to both pairwise and higher
      order spin correlations. The effect of limited experimental data on the results
      is also considered. Second, we re-analyse published experimental data on the
      frustrated system Y0.5Ca0.5BaCo4O7. The results from spinvert refinement indicate
      similarities between Y0.5Ca0.5BaCo4O7 and its parent compound YBaCo4O7, which
      were overlooked in previous analyses using powder data.

PMID- 24140882
TI  - Gene expression patterns combined with bioinformatics analysis identify genes
      associated with cholangiocarcinoma.
AB  - To explore the molecular mechanisms of cholangiocarcinoma (CC), microarray
      technology was used to find biomarkers for early detection and diagnosis. The
      gene expression profiles from 6 patients with CC and 5 normal controls were
      downloaded from Gene Expression Omnibus and compared. As a result, 204
      differentially co-expressed genes (DCGs) in CC patients compared to normal
      controls were identified using a computational bioinformatics analysis. These
      genes were mainly involved in coenzyme metabolic process, peptidase activity and
      oxidation reduction. A regulatory network was constructed by mapping the DCGs to
      known regulation data. Four transcription factors, FOXC1, ZIC2, NKX2-2 and GCGR,
      were hub nodes in the network. In conclusion, this study provides a set of
      targets useful for future investigations into molecular biomarker studies. 

PMID- 24140883
TI  - Using gene expression programming to infer gene regulatory networks from time
      series data.
AB  - Gene regulatory networks inference is currently a topic under heavy research in
      the systems biology field. In this paper, gene regulatory networks are inferred
      via evolutionary model based on time-series microarray data. A non-linear
      differential equation model is adopted. Gene expression programming (GEP) is
      applied to identify the structure of the model and least mean square (LMS) is
      used to optimize the parameters in ordinary differential equations (ODEs). The
      proposed work has been first verified by synthetic data with noise-free and noisy
      time-series data, respectively, and then its effectiveness is confirmed by three
      real time-series expression datasets. Finally, a gene regulatory network was
      constructed with 12 Yeast genes. Experimental results demonstrate that our model
      can improve the prediction accuracy of microarray time-series data effectively. 

PMID- 24140884
TI  - Skin sensitisation--moving forward with non-animal testing strategies for
      regulatory purposes in the EU.
AB  - In a previous EPAA-Cefic LRI workshop in 2011, issues surrounding the use and
      interpretation of results from the local lymph node assay were addressed. At the
      beginning of 2013 a second joint workshop focused greater attention on the
      opportunities to make use of non-animal test data, not least since a number of in
      vitro assays have progressed to an advanced position in terms of their formal
      validation. It is already recognised that information produced from non-animal
      assays can be used in regulatory decision-making, notably in terms of classifying
      a substance as a skin sensitiser. The evolution into a full replacement for
      hazard identification, where the decision is not to classify, requires the
      generation of confidence in the in vitro alternative, e.g. via formal validation,
      the existence of peer reviewed publications and the knowledge that the assay(s)
      are founded on key elements of the Adverse Outcome Pathway for skin
      sensitisation. It is foreseen that the validated in vitro assays and relevant
      QSAR models can be organised into formal testing strategies to be applied for
      regulatory purposes by the industry. To facilitate progress, the European
      Partnership for Alternative Approaches to animal testing (EPAA) provided the
      platform for cross-industry and regulatory dialogue, enabling an essential and
      open debate on the acceptability of an in vitro based integrated strategy. Based
      on these considerations, a follow up activity was agreed upon to explore an
      example of an Integrated Testing Strategy for skin sensitisation hazard
      identification purposes in the context of REACH submissions. 

PMID- 24140885
TI  - Calorie restriction influences key metabolic enzyme activities and markers of
      oxidative damage in distinct mouse liver mitochondrial sub-populations.
AB  - AIMS: The purpose of the study was to establish if enzyme activities from key
      metabolic pathways and levels of markers of oxidative damage to proteins and
      lipids differed between distinct liver mitochondrial sub-populations, and which
      specific sub-populations contributed to these differences. MAIN METHODS: Male
      C57BL/6J mice were fed non-purified diet for one month then separated into two
      groups, control and calorie-restricted (CR). The two groups were fed semi
      purified diet (AIN93G), with the CR group receiving 40% less calories than
      controls. After two months, enzyme activities and markers of oxidative damage in
      mitochondria were determined. KEY FINDINGS: In all mitochondrial sub-populations,
      enzyme activities and markers of oxidative damage, from control and CR groups,
      showed a pattern of M1>M3>M10. Higher acyl-CoA dehydrogenase (beta-oxidation) and
      beta-hydroxybutyrate dehydrogenase (ketogenesis) activities and lower carbonyl
      and TBARS levels were observed in M1 and M3 fractions from CR mice. ETC enzyme
      activities did not show a consistent pattern. In the Krebs cycle, citrate
      synthase and aconitase activities decreased while succinate dehydrogenase and
      malate dehydrogenase activities increased in the M1 mitochondria from the CR
      versus control mice. SIGNIFICANCE: CR does not produce uniform changes in enzyme
      activities or markers of oxidative damage in mitochondrial sub-populations, with
      changes occurring primarily in the heavy mitochondrial populations.
      Centrifugation at 10,000 g to isolate mitochondria likely dilutes the
      mitochondrial populations which show the greatest response to CR. Use of lower
      centrifugal force (3000 g or lower) may be beneficial for some studies.

PMID- 24140886
TI  - Contribution of macrophages to peripheral neuropathic pain pathogenesis.
AB  - Neuropathic pain pathogenesis is not only confined to changes in the activity of
      neuronal systems, but also involves neuro-immune interactions mediated by
      inflammatory cytokines and chemokines. Among the immune cells involved in these
      interactions, macrophages and their central nervous system counterparts -
      microglia - are actively involved in the generation of peripheral neuropathic
      pain. Depending on the type of lesion (traumatic, metabolic, neurotoxic,
      infections or tumor invasion), the profile of the activated macrophages and
      microglia in terms of time, place and subtype can substantially vary, due to
      their remarkable plasticity that allows tuning their physiology according to
      microenvironmental signals. Knowing what and when specific macrophages activate
      after a peripheral nerve lesion could help in creating a pattern that can be
      further used to target the macrophages with cell-specific therapeutics and remit
      chronicization and complications of neuropathic pain. This minireview summarizes
      recent findings on the specific contribution of macrophages in different
      neuropathic pain models. 

PMID- 24140887
TI  - Luteolin attenuates TGF-beta1-induced epithelial-mesenchymal transition of lung
      cancer cells by interfering in the PI3K/Akt-NF-kappaB-Snail pathway.
AB  - AIMS: Luteolin is a natural flavonoid that possesses a variety of pharmacological
      activities, such as anti-inflammatory and anti-cancer abilities. Whether luteolin
      regulates the transformation ability of lung cancer cells remains unclear. The
      current study aims to uncover the effects and underlying mechanisms of luteolin
      in regulation of and epithelial-mesenchymal transition of lung cancer cells. MAIN
      METHODS: The lung adenocarcinoma A549 cells were used in this experiment; the
      cells were pretreated with luteolin followed by administration with TGF-beta1.
      The expression levels of various cadherin and related upstream regulatory modules
      were examined. KEY FINDINGS: Pretreatment of luteolin prevented the morphological
      change and downregulation of E-cadherin of A549 cells induced by TGF-beta1. In
      addition, the activation of PI3K-Akt-IkappaBa-NF-kappaB-Snail pathway which leads
      to the decline of E-cadherin induced by TGF-beta1 was also attenuated under the
      pretreatment of luteolin. SIGNIFICANCE: We provide the mechanisms about how
      luteolin attenuated the epithelial-mesenchymal transition of A549 lung cancer
      cells induced by TGF-beta1. This finding will strengthen the anti-cancer effects
      of flavonoid compounds via the regulation of migration/invasion and EMT ability
      of various cancer cells.

PMID- 24140888
TI  - Cardioprotection of H2S by downregulating iNOS and upregulating HO-1 expression
      in mice with CVB3-induced myocarditis.
AB  - AIMS: To explore the effects and potential mechanisms of hydrogen sulfide (H2S)
      in CVB3-induced mice with myocarditis. MAIN METHODS: A total of 75 six-week-old
      inbred male Balb/c mice were divided randomly into four groups (N, C, P and S).
      Group N was the negative control. The others were inoculated intraperitoneally
      (i.p.) with CVB3. Subsequently, groups P and S were injected i.p. once a day with
      DL-Proparglygylcine (PAG) and NaHS respectively. Group C was the positive
      control. Inducible nitric oxide synthase (iNOS) and heme oxygenase-1(HO-1)
      expression on cardiac tissues were evaluated by histopathological examination,
      immunohistochemistry, RT-PCR and Western blot. KEY FINDINGS: The heart-weight to
      body-weight (HW/BW) ratio, the histologic scores and the iNOS mRNA and protein
      expression levels were higher, and the HO-1 mRNA and protein expression levels
      were lower in mice treated with PAG than those mice solely inoculated with CVB3.
      Mice in group S had a significant decreased in the HW/BW ratio, the histologic
      scores and the iNOS mRNA and protein expression levels, and had a significant
      increased in the HO-1 mRNA and protein expression levels compared to the mice in
      group C. H2S can attenuate inflammatory cell infiltration, alleviate cardiac
      edema, and limit myocardial lesions. SIGNIFICANCE: Our data support that H2S can
      inhibit iNOS overexpression and induce HO-1 expression, both of which contribute
      to the cardioprotection of H2S in CVB3-induced mice myocarditis.

PMID- 24140889
TI  - Advances in pathogenesis and current therapeutic strategies for cardiorenal
      syndrome.
AB  - Cardiorenal syndrome (CRS) is characterized as a syndrome involving both the
      cardiovascular system and kidneys. Due to its complexity and high mortality, it
      has becoming a significant burden and a universal clinical challenge to society
      worldwide. The mechanisms underlying CRS are potentially multifactorial,
      including hemodynamic alterations, neurohormonal activation, inflammation,
      oxidative stress, iron disorders, anemia, and mineral metabolic derangements.
      Despite the understanding and awareness of CRS gaining attention, appropriate
      approaches to manage CRS remain deficient. Loop diuretic and thiazides,
      inhibition of the renin-angiotensin system, vitamin D receptor activation and
      dopamine and natriuretic peptides could potentially be helpful to improve the
      prognosis of CRS. Ultrafiltration might be an alternative therapeutic strategy
      for the loss of liquid. However, adenosine receptor antagonists do not appear to
      be superior to furosemide in CRS treatment. novel therapeutic approaches should
      be explored. 

PMID- 24140890
TI  - Dynamic expression of the vertebrate-specific protein Nucks during rodent
      embryonic development.
AB  - The nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) is a
      highly phosphorylated nuclear protein that is overexpressed in many types of
      cancer. The flexibility of NUCKS and its extensive posttranslational
      modifications indicate that it is multifunctional, and its expression in most
      cell types suggests a housekeeping function. However, spatiotemporal expression
      of the Nucks protein during rodent development has not been reported. Thus, we
      investigated the expression of both the Nucks mRNA and protein during rat and
      mouse development by immunohistochemistry, in situ hybridization, Western
      immunoblotting, and reverse-transcription PCR analysis. We also used BLAST
      analysis against expressed sequence tag databases to determine whether a NUCKS
      homologue is expressed in invertebrate organisms. We found that Nucks expression
      increased during the initial stages of embryonic development, and then gradually
      decreased until birth in all tissues except the nervous tissue and muscle fibers.
      Interestingly, the expression of Nucks was very strong in migrating neural crest
      cells at E13.5 and ectoderm-derived tissues. In most tissues analyzed, the levels
      of Nucks correlated with the levels of Bax and activated caspase-3, which are
      indicative of apoptosis. Moreover, Nucks was upregulated very early during
      neuronal apoptosis in vitro. Expression analysis revealed that no transcript with
      close homology to the Nucks gene was present in invertebrates. The expression of
      Nucks in both proliferating and quiescent cells and its correlation with Bax
      levels and apoptosis strongly suggest that Nucks plays complex roles in cell
      homeostasis. Furthermore, the lack of homology in invertebrate organisms
      indicates a specific role for Nucks in vertebrate embryogenesis. 

PMID- 24140891
TI  - Possible involvement of microRNAs in vascular damage in experimental chronic
      kidney disease.
AB  - Chronic kidney disease (CKD) is associated with vascular calcifications and
      atherosclerosis. There is a need for novel predictors to allow earlier diagnosis
      of these disorders, predict disease progression, and improve assessment of
      treatment response. We focused on microRNAs since they are implicated in a
      variety of cellular functions in cardiovascular pathology. We examined changes of
      microRNA expression in aortas of CKD and non-CKD wild type mice and
      apolipoprotein E knock-out mice, respectively. Both vascular smooth muscle
      specific miR-143 and miR-145 expressions were decreased in states of
      atherosclerosis and/or CKD or both, and the expression level of protein target
      Myocardin was increased. The inflammatory miR-223 was increased in more advanced
      stages of CKD, and specific protein targets NFI-A and GLUT-4 were dramatically
      decreased. Expression of miR-126 was markedly increased and expression of protein
      targets VCAM-1 and SDF-1 was altered during the course of CKD. The drug
      sevelamer, commonly used in CKD, corrected partially these changes in microRNA
      expression, suggesting a direct link between the observed microRNA alterations
      and uremic vascular toxicity. Finally, miR-126, -143 and -223 expression levels
      were deregulated in murine serum during the course of experimental CKD. In
      conclusion, these miRNAs could have role(s) in CKD vascular remodeling and may
      therefore represent useful targets to prevent or treat complications of CKD. 

PMID- 24140892
TI  - Structural analysis of brain ganglioside acetylation patterns in mice with
      altered ganglioside biosynthesis.
AB  - Gangliosides are sialylated membrane glycosphingolipids especially abundant in
      mammalian brain tissue. Sialic acid O-acetylation is one of the most common
      structural modifications of gangliosides which considerably influences their
      chemical properties. In this study, gangliosides extracted from brain tissue of
      mice with altered ganglioside biosynthesis (St8sia1 null and B4galnt1 null mice)
      were structurally characterized and their acetylation pattern was analyzed.
      Extracted native and alkali-treated gangliosides were resolved by high
      performance thin layer chromatography. Ganglioside mixtures as well as separated
      individual ganglioside fractions were further analyzed by tandem mass
      spectrometry. Several O-acetylated brain ganglioside species were found in
      knockout mice, not present in the wild-type mice. To the best of our knowledge
      this is the first report on the presence of O-acetylated GD1a in St8sia1 null
      mice and O-acetylated GM3 species in B4galnt1 null mice. In addition, much higher
      diversity of abnormally accumulated brain ganglioside species regarding the
      structure of ceramide portion was observed in knockout versus wild-type mice.
      Obtained findings indicate that the diversity of brain ganglioside structures as
      well as acetylation patterns in mice with altered ganglioside biosynthesis, is
      even higher than previously reported. Further investigation is needed in order to
      explore the effects of acetylation on ganglioside interactions with other
      molecules and consequently the physiological role of acetylated ganglioside
      species. 

PMID- 24140893
TI  - Synthesis of O- and C-glycosides derived from beta-(1,3)-D-glucans.
AB  - A series of beta-(1,3)-d-glucans have been synthesized incorporating structural
      variations specifically on the reducing end of the oligomers. Both O- and C
      glucosides derived from di- and trisaccharides have been obtained in good overall
      yields and with complete selectivity. Whereas the O-glycosides were obtained via
      a classical Koenigs-Knorr glycosylation, the corresponding C-glycosides were
      obtained through allylation of the anomeric carbon and further cross-metathesis
      reaction. Finally, the compounds were evaluated against two glycosidases and two
      endo-glucanases and no inhibitory activity was observed. 

PMID- 24140894
TI  - Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a
      mouse model of Parkinson's disease.
AB  - The long-term use of levodopa (L-DOPA) in Parkinson's disease (PD) results in the
      development of abnormal involuntary movements called L-DOPA-induced dyskinesias.
      Increasing evidences suggest that the endocannabinoid system may play a role in
      the modulation of dyskinesias. In this work, we assessed the antidyskinetic
      effect of the endocannabinoid analog oleoylethanolamide (OEA), an agonist of
      PPARalpha and antagonist of TRPV1 receptors. We used a hemiparkinsonian model of
      PD in mice with 6-OHDA striatal lesion. The chronic L-DOPA treatment developed
      intense axial, forelimb and orolingual dyskinetic symptoms, as well as
      contralateral rotations. Treatment with OEA reduced all these symptoms without
      reducing motor activity or the therapeutic motor effects of L-DOPA. Moreover, the
      OEA-induced reduction in dyskinetic behavior correlated with a reduction in
      molecular correlates of dyskinesia. OEA reduced FosB striatal overexpression and
      phosphoacetylation of histone 3, both molecular markers of L-DOPA-induced
      dyskinesias. We found that OEA antidyskinetic properties were mediated by TRPV1
      receptor, as pretreatment with capsaicin, a TRPV1 agonist, blocked OEA
      antidyskinetic actions, as well as the reduction in FosB- and pAcH3
      overexpression induced by L-DOPA. This study supports the hypothesis that the
      endocannabinoid system plays an important role in the development and expression
      of dyskinesias and might be an effective target for the treatment of L-DOPA
      induced dyskinesias. Importantly, there was no development of tolerance to OEA in
      any of the parameters we examined, which has important implications for the
      therapeutic potential of drugs targeting the endocannabinoid system. 

PMID- 24140895
TI  - Transcriptional variation in response to salt stress in commonly used Arabidopsis
      thaliana accessions.
AB  - Transcriptional variation is increasingly recognized as a component of genetic
      diversity and environmental adaptation. It can also provide insights into stress
      responsive determinants and underlying adaptive mechanisms. Prior studies showed
      phenotypic differences in response to salinity stress for two widely used
      Arabidopsis thaliana accessions, Wassilewskija-2 (Ws) and Columbia-0 (Col). This
      study examined changes in global gene expression in relation to differences in
      response to salt stress among Ws, Col, and the glabrous mutant of Col [Col(gl)].
      Transcripts most highly affected by accession and salt stress were related to
      abiotic or biotic stress responses. Approximately 60% of salt-induced changes in
      Ws overlapped with changes in Col, suggesting common salt stress responses.
      However, a markedly greater number of genes was altered in the highly salt
      sensitive Col, likely reflecting both adaptive responses and salt injury. The
      Col(gl) transcriptome was least affected by salt. Many salt-responsive
      transcripts observed in Col were altered in Col(gl) prior to salt stress,
      indicating that even without salt, the gl1-1 mutation induced a suite of stress
      responsive genes. Regardless of salt stress, there were greater transcriptomic
      differences between Col and Col(gl) than between Col and Ws. The transcript
      expression differences between [Ws vs. Col] and [Col(gl) vs. Col] formed largely
      non-overlapping sets. Thus, although Ws, Col and Col(gl) are commonly and
      sometimes interchangeably used, here they displayed distinct responses.
      Collectively, their observed expression differences likely reflect a combination
      of adaptive traits, response to injury, or phenotypic buffering of mutational
      effects. 

PMID- 24140896
TI  - Preliminary results of prophylactic HIPEC in patients with locally advanced
      gastric cancer.
AB  - BACKGROUND: The prognosis of locally advanced Gastric Cancer following surgical
      therapy alone is poor. Peritoneum represents a preferential site of dissemination
      in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used
      in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal
      carcinomatosis (PC). Aim of our preliminary experience is reporting our data on
      prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC.
      METHODS: Eleven patients underwent P-HIPEC at our General and Emergency Surgery
      Department. All the patients were affected of high risk GC: serosa invasive
      tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA
      mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or
      D2+ were performed. All the anastomoses were made before HIPEC. The procedure was
      carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post
      operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition
      was started precociously (day 5) also according with bowel movements and
      stool/gas passage. Follow-up took place in all patients at 1 month from surgery
      then every 6 months for 2 years and every 12 months for the following years.
      RESULTS: In four patients a neoadjuvant treatment was scheduled due to T or N
      stage at pre-operative evaluation. Gastric resection was guided on tumor location
      while the choice of performing a D2 or D2 + lymphadenectomy was up to
      preoperative imaging and intra-operative nodal status. No intra-operative
      complications were recorded. Median operation time was 398 minutes. In our series
      we recorded 20 adverse events. Median number for each patient was 1 adverse
      effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3)
      that did not require any surgical treatment. Only one patient with duodenal stump
      dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for
      severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative
      mortality was 18%. Both patients were older then 70 years old. Median hospital
      stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6
      months and median DFS was 20 months. Only one patient developed a peritoneal
      recurrence at 12 months and died for disease progression. Seven patients are
      still alive and disease free at last follow-up. One patient affected of variable
      immunodeficiency died at 9 months for pulmonary sepsis without any sign of local
      recurrence. CONCLUSIONS: Peritoneal dissemination appears to be a strong
      determinant in defining GC patients prognosis. Even after curative resection,
      peritoneal recurrence develops in about 60% of the patients with T3 and T4
      tumors, and up to 40% of resected gastric cancer patients die as a direct result
      of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was
      associated with a significant improvement in survival compared to surgery alone
      in patients affected of GC with resectable PC. At present day there are not
      studies evaluating the role of P-HIPEC in patients at high risk of developing PC.
      The rationale of P-HIPEC is based on the concept that positive peritoneal lavage
      is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM
      classification. Also analogous is the median survival of this 2 groups of
      patients. Detection of peritoneal micrometastases with cytologic examination has
      been considered a major method to predict peritoneal recurrences; the sensitivity
      of this assay is low. Recently, molecular approaches using real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) technique has made possible the
      increase in the sensitivity. We can conclude, although the preliminary
      experience, that prophylactic HIPEC in locally advanced gastric cancer is
      feasible, increasing median survival compared to surgery alone. For sure this
      procedure need to be performed in the highly specialized centres strongly
      respecting the eligibility criteria.

PMID- 24140897
TI  - An expansin from the marine bacterium Hahella chejuensis acts synergistically
      with xylanase and enhances xylan hydrolysis.
AB  - HcEXLX2 is a bacterial expansin found in a marine bacterium, Hahella chejuensis.
      Previously, HcEXLX2 was reported to act synergistically with a commercial
      cellulase preparation on the cellulose hydrolysis. The aim of the present study
      was to investigate the possible synergistic activity of HcEXLX2 with an endo-type
      xylanase from Saccharophagus degradans 2-40(T) (Xyn10C) in the hydrolysis of
      xylan. When 160 MUg of HcEXLX2 was incubated with 12 MUg of Xyn10C, the yield of
      reducing sugar increased 3.1 times when compared to that without HcEXLX2. The
      optimal temperature and pH for the synergism of HcEXLX2 with Xyn10C were 30
      degrees C and pH 7, respectively. In addition, binding experiments revealed that
      HcEXLX2 binds to xylan more preferentially than to Avicel. These results imply
      that HcEXLX2 could be used as an accessory protein to boost the activity of
      xylanase if its synergistic effect is strengthened at lower dosages.

PMID- 24140898
TI  - Glucose content in the liquid hydrolysate after dilute acid pretreatment is
      affected by the starch content in rice straw.
AB  - Lignocellulosic biomass, such as rice straw, is often utilized as a bioresource
      after being hydrolyzed using dilute acid and separated into liquid hydrolysate
      and acid-insoluble residue. However, the biomass component that determines the
      distribution between liquid hydrolysate and acid-insoluble residue has not yet
      been clarified. In this study, the glucose content in the liquid hydrolysate and
      weight of acid-insoluble residue of 13 rice cultivars were analyzed. Starch
      content was positively correlated with glucose content in the liquid hydrolysate,
      and negatively correlated with acid-insoluble residue weight. These results
      indicate that the glucose in the liquid hydrolysate is mainly liberated from
      starch rather than cellulose in the rice straw. These observations suggest that
      starch content is a good indicator of the glucose distribution between the liquid
      hydrolysate and insoluble residue. 

PMID- 24140899
TI  - Continuous co-fermentation of cellobiose and xylose by engineered Saccharomyces
      cerevisiae.
AB  - Simultaneous fermentation of cellobiose and xylose by an engineered Saccharomyces
      cerevisiae has been demonstrated in batch fermentation, suggesting the
      feasibility of continuous co-fermentation of cellulosic sugars. As industrial S.
      cerevisiae strains have known to possess higher ethanol productivity and
      robustness compared to laboratory S. cerevisiae strains, xylose and cellobiose
      metabolic pathways were introduced into a haploid strain derived from an
      industrial S. cerevisiae. The resulting strain (JX123-BTT) was able to ferment a
      mixture of cellobiose and xylose simultaneously in batch fermentation with a high
      ethanol yield (0.38 g/g) and productivity (2.00 g/L . h). Additionally, the JX123
      BTT strain co-consumed glucose, cellobiose, and xylose under continuous culture
      conditions at a dilution rate of 0.05 h(-1) and produced ethanol resulting in
      0.38 g/g of ethanol yield and 0.96 g/L . h of productivity. This is the first
      demonstration of co-fermentation of cellobiose and xylose by an engineered S.
      cerevisiae under continuous culture conditions.

PMID- 24140900
TI  - [Usefulness of subtraction computed tomography angiography employing orbital
      synchronized helical scanning for diagnosis of lower extremity arteries with
      vessel wall calcification].
AB  - PURPOSE: Massive calcification complicates the diagnosis of the blood vessel
      lumen in computed tomography angiography (CTA) of the arteries of the lower
      extremities. The purpose of this study was to evaluate subtraction CTA with the
      use of orbital synchronized helical scanning (OS-SCTA). METHOD: Phantom study: We
      performed OS-SCTA and non-OSCTA of a calcified vessel phantom (psi2.5 mm), and
      compared them with a non-calcified vessel phantom as the reference by full width
      at half maximum (FWHM) and full width at tenth maximum (FWTM) of maximum
      intensity projection (MIP) images. Clinical study: 58 patients with peripheral
      artery disease who were referred for angiography also underwent OS-SCTA. OS-SCTA
      was produced using MIP images. Findings were graded according to three
      categories: (1) stenosis greater than 50% or occluded; (2) stenosis less than
      50%; (3) not detected due to insufficient image quality. OS-SCTA findings were
      compared with the angiographic findings for each arterial segment. RESULTS: In
      the phantom study, FWHM showed no significant difference between OS-SCTA and the
      reference (P=0.135), whereas FWTM showed a significant difference (P<0.001). FWHM
      and FWTM showed a significant difference between non-OS-SCTA and the reference
      (P<0.001), due to misregistration with helical artifacts. In a clinical study
      comparing OS-SCTA with angiography, the sensitivity and specificity were 93.3%
      and 95.1% in calcified segments, 91.8% and 93.9% in non-calcified segments, and
      92.2% and 94.6% in all segments. There was no significant difference between
      calcified segments and non-calcified segments (sensitivity: P=0.568, specificity:
      P=0.549). CONCLUSION: OS-SCTA is beneficial for the diagnosis of lower extremity
      arteries with vessel wall calcification, since it shows detection accuracy
      comparable to that of angiography.

PMID- 24140901
TI  - [Detailed analysis of multi-leaf collimator movement during radiation delivery
      using an in-house-developed program].
AB  - Multi-leaf collimators (MLCs) are used to modulate intensity during intensity
      modulated radiation therapy (IMRT). Evaluation of MLC movement in IMRT is
      important, since the accuracy of MLC movements affects the dose distribution.
      This evaluation is conventionally performed using an attached Dynalog File Viewer
      (DFV). However, due to its being an overall evaluation, it is not possible to
      discover significant errors. In this study, we developed software that permits
      easy analysis of MLC movements that can be used to retrospectively evaluate MLC
      movement during irradiation. We also evaluated the usefulness of our in-house
      program and confirmed its potential for use in clinical scenarios. We created a
      program that can read MLC logfiles using Visual Basic 6.0 and visualize the
      temporal changes and movements of the MLC. To evaluate our in-house program's
      efficacy in analyzing dynamic MLC-QA (quality assurance), we compared the
      numerical results yielded by our in-house program and the DFV. The results showed
      that our in-house program was able to reveal errors below the error root mean
      square (RMS) values obtained using the DFV. Using irregular surface compensator
      (ISC) irradiation conditions in a clinical context, we compared our in-house
      program with the DFV and, using RMS analysis, identified cases that showed
      excessive error. Our in-house program can also be used to investigate whether
      unacceptable errors are present, as well as their cause, when using the MLC, as
      it allows easy real-time observation and evaluation of MLC movements. An
      additional benefit is that collecting the MLC logfile during actual treatment
      also allows it to be evaluated retrospectively after continuous MLC operation. 

PMID- 24140902
TI  - [Proposal for an auxiliary tool designed to reduce retake rates for lateral
      radiography of the knee joint].
AB  - The reproducibility of lateral radiography of the knee joint in the lateral
      position is low because patient positioning can be easily affected by passive
      rotation of the knee joint. We calculated the correction angle of the femoral
      external rotation and the lower leg elevation and developed our own auxiliary
      tool for obtaining a lateral view image. We were able to obtain, in a single
      attempt, an image with misalignment of the condyle limited to less than 7 mm. Our
      tool also contributed to the reduction of the re-imaging rate, suggesting its
      usefulness in contributing to a lower re-imaging rate for lateral radiography of
      the knee joint. 

PMID- 24140903
TI  - [Can fruits and vegetables be used as substitute phantoms for normal human brain
      tissues in magnetic resonance imaging?].
AB  - Various custom-made phantoms designed to optimize magnetic resonance imaging
      (MRI) sequences have been created and subsequently reported in JSRT. However,
      custom-made phantoms that correctly match the T1-value and T2-values of human
      brain tissue (gray matter and white matter) cannot be made easily or quickly. The
      aim of this project was to search for alternative materials, such as fruits and
      vegetables, for optimizing MRI sequences. The following eight fruits and
      vegetables were investigated: apple, tomato, melon, apple mango (Mangifera
      indica), banana, avocado, peach, and eggplant. Their potential was studied for
      use in modeling phantoms of normal human brain tissues. MRI (T1- and T2-weighted
      sequences) was performed on the human brain and the fruits and vegetables using
      various concentrations of contrast medium (gadolinium) in the same size tubes as
      the custom-made phantom. The authors compared the signal intensity (SI) in human
      brain tissue (gray matter and white matter) with that of the fruits and the
      custom-made phantom. The T1 and T2 values were measured for banana tissue and
      compared with those for human brain tissue in the literature. Our results
      indicated that banana tissue is similar to human brain tissue (both gray matter
      and white matter). Banana tissue can thus be employed as an alternative phantom
      for the human brain for the purpose of MRI. 

PMID- 24140904
TI  - [Accuracy estimation of non-invasive X-ray output analyzer].
AB  - This study estimated the accuracy of an X-ray analyzer by comparing it with an
      ionization chamber and a tube voltage current meter, and investigated whether it
      was usable as a substitute for a reference meter for output measurements for
      quality control purposes. The X-ray output analyzer used was a Piranha (RTI
      Electronics), a non-invasive instrument. The two subjects of measurements were as
      follows: the tube voltage, exposure, and half-value layer used in ordinary X-ray
      radiographic system equipment, and the exposure and half-value layer in X-ray
      equipment for mammographic systems. The results for a conventional radiographic
      system showed the error rates for tube voltage, exposure, and half value layer to
      be within +/-1.0%, +/-1.8%, and +/-4.3%, respectively. The Piranha is not
      influenced by the dependence of the beam quality in a range of the tube voltage
      in clinical use. In X-ray equipment for mammographic system results, error rates
      for exposure and half value layer were +/-2.2% and within +/-4.0%, respectively.
      We conclude that it is possible to use the Piranha as an alternative reference
      meter for quality control of X-ray equipment for typical radiographic and
      mammographic systems. 

PMID- 24140905
TI  - [Comparison of the absorbed dose at calibration depth of photon beams using the
      Japan Society of Medical Physics 12 beam quality conversion factor in the
      presence or absence of a waterproofing sleeve].
AB  - In standard external beam radiotherapy dosimetry, which is based on absorbed dose
      by water, the absorbed dose at any calibration depth is calculated using the same
      beam quality conversion factor, regardless of the presence or absence of a
      waterproofing sleeve. In this study, we evaluated whether there were differences
      between absorbed doses at calibration depths calculated using a beam quality
      conversion factor including a wall correction factor that corresponds to a
      waterproofing sleeve thickness of 0.3 mm, and without a waterproofing sleeve. The
      Japan Society of Medical Physics (JSMP) has reported that the uncertainty of the
      results using a beam quality conversion factor that included a wall correction
      factor corresponding to a waterproofing sleeve thickness of 0.3 mm, regardless of
      the presence or absence of the sleeve, was 0.2%. This uncertainty proved to be in
      agreement with the reported range. 

PMID- 24140906
TI  - [Development of all-in-one multi-slit equipment for measurements of the input
      output characteristic of a phosphor plate].
AB  - An input-output characteristic curve is an essential piece of information for
      analyzing medical images taken using a phosphor plate. In the multi-slit method,
      an actuator moves shields that have numerous slits during X-ray irradiation.
      Numerous data can be measured by one-time irradiation, so the fading effect is
      negligibly small. This method was recently proposed by Takegami et al., but their
      equipment consisted of large multiple compositions. The aim of this study was to
      fabricate a new handy type equipment that combines multiple productions into one
      small production. In this paper, we propose an idea for downscaling the size of
      the equipment, and report that the same input-output characteristic is obtained
      using our newly proposed method. 

PMID- 24140907
TI  - [5. Diagnosis of ischemic heart disease -coronary angiography-].

PMID- 24140908
TI  - [MR imaging in cerebrovascular disease and selection of examination protocol].

PMID- 24140910
TI  - [Report of Trade Modernization Committee activity].

PMID- 24140912
TI  - Joint estimation of shape and deformation for the detection of lesions in dynamic
      contrast-enhanced breast MRI.
AB  - We propose a mathematical framework for simultaneously delineating the boundary
      of object and estimating its temporal motion in the application of lesion
      detection in a dynamic contrast-enhanced (DCE) breast MRI sequence where both the
      appearance and the shape of region of interest is assumed to change in time. A
      unified energy functional for a joint segmentation and registration is proposed
      based on the assumption that the statistical properties of dynamic intensity
      curves within a region of interest are homogeneous. Our algorithm is designed to
      provide the morphological properties of the enhanced region and its dynamic
      intensity profiles, called kinetic signatures, in the analysis of DCE imagery
      since these features are considered as significant cues in understanding images.
      The proposed energy comprises a combination of a segmentation energy and a
      registration energy. The segmentation energy is developed based on a convex
      formulation being insensitive to the initialization. The registration energy is
      designed to compensate motion artifacts that are usually involved in the temporal
      imaging procedure. The major objective of this work is to provide a mathematical
      framework for a joint segmentation and registration on a dynamic sequence of
      images, and we demonstrate the mutual benefit of the estimation of temporal
      deformations for the registration step and the localization of regions of
      interest for the segmentation step. The effectiveness of the developed algorithm
      has been demonstrated on a number of clinical DCE breast MRI data in the
      application of breast lesion detection and the results show its potential to
      improve the accuracy and the efficiency in the diagnosis of breast cancer. 

PMID- 24140913
TI  - Towards a robust ad hoc data correction approach that yields reliable atomic pair
      distribution functions from powder diffraction data.
AB  - We examine the equations to obtain atomic pair distribution functions (PDFs) from
      x-ray, neutron and electron powder diffraction data with a view to obtaining
      reliable and accurate PDFs from the raw data using a largely ad hoc correction
      process. We find that this should be possible under certain circumstances that
      hold, to a reasonably good approximation, in many modern experiments. We describe
      a variational approach that could be applied to find data correction parameters
      that is highly automatable and should require little in the way of user inputs
      yet results in quantitatively reliable PDFs, modulo unknown scale factors that
      are often not of scientific interest when profile fitting models are applied to
      the data with scale factor as a parameter. We have worked on a particular
      implementation of these ideas and demonstrate that it yields PDFs that are of
      comparable quality to those obtained with the existing x-ray data reduction
      program PDFgetX2. This opens the door to rapid and highly automated processing of
      raw data to obtain PDFs. 

PMID- 24140914
TI  - Study of interaction between human serum albumin and three antioxidants: ascorbic
      acid, alpha-tocopherol, and proanthocyanidins.
AB  - Ascorbic acid, alpha-tocopherol and proanthocyanidins are three classic dietary
      antioxidants. In this study, the interaction between the three antioxidants and
      human serum albumin (HSA) was investigated by several spectroscopic techniques.
      Experimental results proved that the three antioxidants quench the fluorescence
      of HSA through a static (proanthocyanidins) or static-dynamic combined quenching
      mechanism (ascorbic acid and alpha-tocopherol). Thermodynamic investigations
      revealed that the combination between ascorbic acid or proanthocyanidins and HSA
      was driven mainly by electrostatic interaction, and the hydrophobic interactions
      play a major role for alpha-tocopherol-HSA association. Binding site I was found
      to be the primary binding site for ascorbic acid and proanthocyanidins, and site
      II for alpha-tocopherol. Additionally, the three antioxidants may induce
      conformational and microenvironmental changes of HSA. 

PMID- 24140915
TI  - Design, chemical synthesis of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione
      derivatives and biological activity against enoyl-ACP reductase (InhA) and
      Mycobacterium tuberculosis.
AB  - We report here the discovery, synthesis and screening results of a series of 3
      (9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives as a novel class of potent
      inhibitors of Mycobacterium tuberculosis H37Rv strain as well as the enoyl acyl
      carrier protein reductase (ENR) InhA. Among them, several compounds displayed
      good activities against InhA which is one of the key enzymes involved in the type
      II fatty acid biosynthesis pathway of the mycobacteria cell wall. Furthermore,
      some exhibited promising activities against M. tuberculosis and multi-drug
      resistant M. tuberculosis strains. 

PMID- 24140916
TI  - Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-oxadiazole
      derivatives as antimicrobial and anti-tubercular agents.
AB  - We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based
      1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial,
      anti-fungal and anti-tubercular activities. Promisingly, most of the compounds
      showed equal or more potency than standard ciprofloxacin against Staphylococcus
      aureus, Bacillus subtilis and Escherichia coli. Compound 5e exhibited highest
      anti-tubercular activity (0.46 MUg/mL) close to that of standard Isoniazid (0.40
      MUg/mL). Equal antifungal activity (1.56 MUg/mL) compared to standard
      Amphotericin-B was shown by most of the compounds. All the N-methylated compounds
      showed more potent to equal activity against MSSA (MIC 0.39-1.56 MUg/mL) and MRSA
      (MIC 0.78-1.56 MUg/mL). All compounds were tested for mammalian cell toxicity
      using VERO cell line and were found to be non-toxic.

PMID- 24140917
TI  - Physiological and serum biochemical changes associated with rayless goldenrod
      (Isocoma pluriflora) poisoning in goats.
AB  - Rayless goldenrod (Isocoma pluriflora) has been known to be toxic to livestock in
      the southwestern United States for many years; however, chemical composition of
      the plant as well as the dosage and duration required to cause toxicosis have not
      been completely described. Tremetol, the historical toxin, is actually a mixture
      of alcohols and ketones. Though not completely confirmed experimentally, the
      toxic compounds are believed to be benzofuran ketones that include tremetone,
      dehydrotremetone, 3-hydroxytremetone, and 3-oxyangeloyl-tremetone. The objectives
      of this study were to determine the dosage of benzofuran ketones and the duration
      of exposure to these compounds required to produce clinical signs of poisoning in
      Spanish goats and to document the pathophysiological changes associated with
      rayless goldenrod poisoning in goats. Goats dosed with rayless goldenrod
      containing 40 and 60 mg/kg BW of benzofuran ketones for 4 or 5 days, showed
      clinical signs of toxicosis that included trembles, and exercise intolerance seen
      as reluctance to perform on the treadmill, significantly increased resting and
      working heart rates and prolonged heart rate recovery following exercise. The
      affected goats also had significant serum biochemical changes that included
      increased concentrations of cardiac troponin I and increased activities of
      aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and
      creatine kinase. Exercise intolerant animals also had extensive degeneration and
      necrosis within nearly all skeletal muscles. Some goats dosed with 10 and 20
      mg/kg BW of benzofuran ketones began to show some signs of poisoning on the last
      day of the study. In conclusion, benzofuran ketones at doses at or above 40 mg/kg
      BW for longer than 4 or 5 days are toxic and produce disease similar to that
      described in clinical rayless goldenrod poisoning. Additionally, smaller
      benzofuran ketone doses (10 and 20 mg/kg BW) for longer durations also cause the
      disease. The physiologic findings indicated that though there may be some
      myocardial changes, the majority of the clinical disease in goats is due to
      skeletal muscle degeneration and necrosis. More work is needed to determine the
      toxicity and physiologic effects of individual benzofuran ketones and to develop
      a model that better predicts the risk of poisoning and methods to avoid poisoning
      by plants containing benzofuran ketones. 

PMID- 24140918
TI  - Analytical workflow for rapid screening and purification of bioactives from venom
      proteomes.
AB  - Animal venoms are important sources for finding new pharmaceutical lead
      molecules. We used an analytical platform for initial rapid screening and
      identification of bioactive compounds from these venoms followed by fast and
      straightforward LC-MS only guided purification to obtain bioactives for further
      chemical and biological studies. The analytical platform consists of a nano-LC
      separation coupled post-column to high-resolution mass spectrometry and parallel
      on-line bioaffinity profiling for the acetylcholine binding protein (AChBP) in a
      chip based fluorescent enhancement based bioassay. AChBP is a stable structural
      homologue of the extracellular ligand binding domain of the alpha7-nicotinic
      acetylcholine receptor (alpha7-nAChR). This receptor is an extensively studied
      medicinal target, previously associated with epilepsy, Alzheimer's, schizophrenia
      and anxiety. The workflow is demonstrated with the venom of the Naja mossambica
      mossambica. Two medium affinity AChBP ligands were found. After subsequent LC-MS
      guided purification of the respective venom peptides, the purified peptides were
      sequenced and confirmed as Cytotoxin 1 and 2. These peptides were not reported
      before to have affinity for the AChBP. The purified peptides can be used for
      further biological studies.

PMID- 24140919
TI  - Methods for simultaneous detection of the cyanotoxins BMAA, DABA, and anatoxin-a
      in environmental samples.
AB  - Blue-green algae, also known as cyanobacteria, can produce several different
      groups of toxins in the environment including hepatotoxins (microcystins),
      neurotoxic non-protein amino acids beta-methylamino-l-alanine (BMAA), and 2,4
      diaminobutyric (DABA), as well as the bicyclic amine alkaloid anatoxin-a. Few
      studies have addressed the methods necessary for an accurate determination of
      cyanotoxins in environmental samples, and none have been published that can
      detect these cyanotoxins together in a single sample. Cyanotoxins occur in a wide
      range of environmental samples including water, fish, and aquatic plant samples.
      Using polymeric cation exchange solid phase extraction (SPE) coupled with liquid
      chromatography and fluorescence detection (HPLC/FD), and liquid chromatography
      ion trap tandem mass spectrometry (LC/MS/MS), these compounds can for the first
      time be simultaneously quantified in a variety of environmental sample types. The
      extraction method for biological samples can distinguish bound and free
      cyanotoxins. Detection limits for water ranged from 5 to 7 MUg/L using HPLC/FD,
      while detection limits for and LC/MS were in the range of 0.8-3.2 MUg/L. 

PMID- 24140920
TI  - First report of the toxin profile of Dinophysis sacculus Stein from LC-MS
      analysis of laboratory cultures.
AB  - Dinophysis sacculus is associated with DSP outbreaks especially in the
      Mediterranean Sea and is supposed to be mildly toxic based on few toxin results
      from field samples. First report of LC-MS analysis of D. sacculus cultures from
      Galicia (NW Spain) showed moderate amounts of OA (7.8 pg cell(-1)) comparable to
      those found in Dinophysis acuminata from the same region, PTX2 (13.2 pg cell(-1))
      and trace amounts of DTX1 (0.8 pg OA equiv. cell(-1)). The contribution of D.
      sacculus to DSP outbreaks in the Galician Northern Rias should not be
      underestimated. 

PMID- 24140921
TI  - The isolation and characterization of lipopolysaccharides from Microcystis
      aeruginosa, a prominent toxic water bloom forming cyanobacteria.
AB  - Massive toxic blooms of cyanobacteria represent a major threat to water supplies
      worldwide, yet serious gaps exist in understanding their complex toxic effects,
      including the role of lipopolysaccharides (LPS). The present comparative study
      focused on the levels and biological activities of LPS isolated from Microcystis
      aeruginosa, which is one of the most globally distributed toxic species. Using
      hot phenol extraction, LPS was isolated from 3 laboratory cultures and 11 natural
      water blooms. It formed 0.2-0.7% of the original dry biomass of the
      cyanobacteria, based on gravimetry. Additional analyses by commercial anti-LPS
      ELISA were correlated with gravimetry but showed concentrations that were about 7
      times lower, which indicated either impurities in isolated LPS or the poor cross
      reactivity of the antibodies used. LPS isolates from M. aeruginosa were potent
      pyrogens in the traditional Limulus amebocyte lysate (LAL)-test, but comparison
      with the PyroGene test demonstrated the limited selectivity of LAL with several
      interferences. The determined pyrogenicity (endotoxin units, EU) ranged from very
      low values in laboratory cultures (less than 0.003 up to 0.008-EU per 100 pg LPS)
      to higher values in complex bloom samples (0.01-0.078 EU per 100 pg of LPS),
      which suggested the role of bloom-associated bacteria in the overall effects.
      Potent pro-inflammatory effects of the studied LPS from both cultures and bloom
      samples were observed in a highly-relevant ex vivo human blood model by studying
      reactive oxygen species production in phagocytes as well as increased productions
      of interleukin 8, IL-8, and tumor necrosis factor alpha, TNF-alpha. LPS from M.
      aeruginosa seem to modulate several pathways involved in the regulation of both
      innate immunity and specific responses. In comparison to the standard pathogenic
      bacterial LPS (World Health Organization Escherichia coli O113:10 endotoxin;
      activity 1 EU per 100 pg), the studied cyanobacterial samples had pyrogenicity
      potencies that were at least 12-times lower. However, the health risks associated
      with LPS from M. aeruginosa should not be underestimated, especially with respect
      to diverse biological effects observed ex vivo and in the case of massive blooms
      in drinking water reservoirs, where the estimated pyrogenicity can reach up to
      46,000 EU per mL of water. 

PMID- 24140922
TI  - Rapid purification of serine proteinases from Bothrops alternatus and Bothrops
      moojeni venoms.
AB  - Envenomation by Bothrops species results, among other symptoms, in hemostatic
      disturbances. These changes can be ascribed to the presence of enzymes, primarily
      serine proteinases some of which are structurally similar to thrombin and
      specifically cleave fibrinogen releasing fibrinopeptides. A rapid, three-step,
      chromatographic procedure was developed to routinely purify serine proteinases
      from the venoms of Bothrops alternatus and Bothrops moojeni. The serine
      proteinase from B. alternatus displays an apparent molecular mass of ~32 kDa
      whereas the two closely related serine proteinases from B. moojeni display
      apparent molecular masses of ~32 kDa and ~35 kDa in SDS-PAGE gels. The partial
      sequences indicated that these enzymes share high identity with serine
      proteinases from the venoms of other Bothrops species. These proteins coagulate
      plasma and possess fibrinogenolytic activity but lack fibrinolytic activity.

PMID- 24140923
TI  - Extraction and partial characterization of venom from the Colombian spider
      Pamphobeteus aff. nigricolor (Aranae:Theraphosidae).
AB  - We report the first studies of characterization and extraction of the
      Pamphobeteus aff. nigricolor (Pocock, 1901) (Aranae:Theraphosidae) venom done in
      Colombia using the electro-stimulation technique previous anesthesia with
      isofluorane. After each extraction process, a low viscosity, colorless venom was
      obtained. This venom showed a 1.01 mg/MUl density and a pH of 5. The humidity
      percentage did not show a significance difference between males and females (P >
      0.05) with a general media of 77.49 +/- 1.74%. In all cases the venom yielded was
      variable between males and females, with a media of 22.45 +/- 5.17 mg (wet
      weight) and 4.58 +/- 0.94 mg (dry weigh), obtaining larger amounts in females,
      28.34 +/- 7.49 mg and 5.69 +/- 1.36 (wet and dry weight respectively). Venom
      showed a hemolytic activity dependent of enzymatic active phospholipase and
      neither coagulant nor proteolytic activities were observed. Electrophoretic
      profile showed a main protein content with a molecular mass below 14 kDa. RP-HPLC
      venom profile revealed a difference among male and female venom's content where
      17 and 21 main fractions were obtained respectively. Three peptides,
      Theraphotoxin-Pn1a, Theraphotoxin-Pn1b and Theraphotoxin-Pn2a, were identified
      using HPLC-nESI-MS/MS. These peptides showed a high identity with other peptides
      found on Theraphosides which are proved to affect voltage-gated calcium channels.

PMID- 24140924
TI  - Local inflammatory reaction induced by Scolopendra viridicornis centipede venom
      in mice.
AB  - Centipede envenomation is generally mild, and human victims usually manifest
      burning pain, erythema and edema. Despite the abundance and ubiquity of these
      animals, centipede venom has been poorly characterized in literature. For this
      reason, the aim of this work was to investigate local inflammatory features
      induced by Scolopendra viridicornis centipede envenomation in mice, evaluating
      edema formation, leukocyte infiltration, production of inflammatory mediators,
      and also performing histological analysis. The highest edematogenic activity
      induced by the venom, determined by plethysmometry, was noticed 0.5 h after
      injection in mice footpad. At 24 h, edema was still detected in animals that
      received 15 and 60 MUg of venom, and at 48 h, only in animals injected with 60
      MUg of venom. In relation to leukocyte count, S. viridicornis venom induced cell
      recruitment, mainly neutrophils and monocytes/macrophages, in all doses and time
      periods analyzed in comparison with PBS-injected mice. An increase in lymphocytes
      was detected especially between 1 and 24 h at 60 MUg dose. Besides, eosinophil
      recruitment was observed mainly for 15 and 60 MUg doses in early time periods.
      Edema formation and cell recruitment were also confirmed by histological
      analysis. Moreover, S. viridicornis venom stimulated the release of IL-6, MCP-1,
      KC, and IL-1beta. Conversely, S. viridicornis venom did not induce the release of
      detectable levels of TNF-alpha. We demonstrated that the edematogenic activity
      induced by S. viridicornis venom was of rapid onset, and the venom stimulated
      secretion of pro-inflammatory mediators which contribute to the inflammatory
      reaction induced by S. viridicornis venom in an experimental model. 

PMID- 24140925
TI  - Inter-molecular correlations in liquid Se2Br2.
AB  - The structure of molecular liquid Se2Br2 was analyzed by means of reverse Monte
      Carlo structural modeling, using a calculation based on high-energy x-ray
      diffraction data. It was found that, between the optical isomers of L and D
      types, the number of L-D neighboring molecular pairs increases, while that of the
      L-L and D-D pairs decreases with increasing temperature. From this temperature
      dependence and from the relaxation mode analysis of quasi-elastic neutron
      scattering spectra, it is reasonable to assume that the presence of L-D pairs
      relates to genuine inter-molecular interactions while the L-L and D-D pairs
      appear due to geometrical packing of the gauche-shaped molecules. 

PMID- 24140926
TI  - Characteristics of child dental neglect: a systematic review.
AB  - OBJECTIVE: Neglect of a child's oral health can lead to pain, poor growth and
      impaired quality of life. In populations where there is a high prevalence of
      dental caries, the determination of which children are experiencing dental
      neglect is challenging. This systematic review aims to identify the features of
      oral neglect in children. METHODS: Fifteen databases spanning 1947-2012 were
      searched; these were supplemented by hand searching of 4 specialist journals, 5
      websites and references of full texts. Included: studies of children 0-18 years
      with confirmed oral neglect undergoing a standardised dental examination;
      excluded: physical/sexual abuse. All relevant studies underwent two independent
      reviews (+/- 3rd review) using standardised critical appraisal. RESULTS: Of 3863
      potential studies screened, 83 studies were reviewed and 9 included (representing
      1595 children). Features included: failure or delay in seeking dental treatment;
      failure to comply with/complete treatment; failure to provide basic oral care; co
      existent adverse impact on the child e.g. pain and swelling. Two studies
      developed and implemented 'dental neglect' screening tools with success. The
      importance of Quality of Life tools to identify impact of neglected dental care
      are also highlighted. CONCLUSIONS: A small body of literature addresses this
      topic, using varying definitions of neglect, and standards of oral examination.
      While failure/delay in seeking care with adverse dental consequences were
      highlighted, differentiating dental caries from dental neglect is difficult, and
      there is a paucity of data on precise clinical features to aid in this
      distinction. CLINICAL SIGNIFICANCE: Diagnosing dental neglect can be challenging,
      influencing a reluctance to report cases. Published evidence does exist to
      support these referrals when conditions as above are described, although further
      quality case control studies defining distinguishing patterns of dental caries
      would be welcome.

PMID- 24140927
TI  - Effects of MK-801 treatment across several pre-clinical analyses including a
      novel assessment of brain metabolic function utilizing PET and CT fused imaging
      in live rats.
AB  - BACKGROUND: Functional imaging studies in schizophrenic patients have
      demonstrated metabolic brain abnormalities during cognitive tasks. This study
      aimed to 1) introduce a novel analysis of brain metabolic function in live
      animals to characterize the hypo- and hyperfrontality phenomena observed in
      schizophrenia and following NMDA antagonist exposure, and 2) identify a robust
      and representative MK-801 treatment regimen that effectively models brain
      metabolic abnormalities as well as a range of established behavioural
      abnormalities representative of schizophrenia. METHODS: The validity of the MK
      801 animal model was examined across several established pre-clinical tests, and
      a novel assessment of brain metabolic function using PET/CT fused imaging. In the
      present study, MK-801 was administered acutely at 0.1 mg/kg and 0.5 mg/kg, and
      sub-chronically at 0.5 mg/kg daily for 7 days. RESULTS: Acute treatment at 0.5
      mg/kg-disrupted facets of memory measured through performance in the 8-arm radial
      maze task and generated abnormalities in sensorimotor gating, social interaction
      and locomotor activity. Furthermore, this treatment regimen induced
      hyperfrontality (increased brain metabolic function in the prefrontal area)
      observed via PET/CT fused imaging in the live rat. LIMITATIONS: While PET and CT
      fused imaging in the live rat offers a functional representation of metabolic
      function, more advanced PET/CT integration is required to analyze more discrete
      brain regions. CONCLUSION: These findings provide insight on the effectiveness of
      the MK-801 pre-clinical model of schizophrenia and provide an optimal regimen to
      model schizophrenia. PET/CT fused imaging offers a highly translatable tool to
      assess hypo- and hyperfrontality in live animals.

PMID- 24140928
TI  - Psychosis effect on hippocampal reduction in schizophrenia.
AB  - INTRODUCTION: In schizophrenia, disruption of the neurodevelopmental processes
      may lead to brain changes and subsequent clinical manifestations of the illness.
      Reports of the progressive nature of these morphological brain changes raise
      questions about their causes. The possible toxic effects of repeated stressful
      psychotic episodes may contribute to the disease progression. OBJECTIVES: To
      analyze the influence of illness duration and previous psychotic episodes on
      hippocampal gray matter volume (GMV) in schizophrenia. METHODS: We performed an
      analysis of hippocampal GMV correlations with illness duration, number of
      previous psychotic episodes, and age in 24 schizophrenia patients and 24 matched
      healthy controls. RESULTS: We found a cluster of GMV voxels in the left
      hippocampal tail that negatively correlated with the number of previous psychotic
      episodes, independent from the effect of age. On the other hand we found no
      effect of illness duration independent of age on the hippocampal GMV. Finally, we
      found a cluster of significant group-by-age interaction in the left hippocampal
      head. CONCLUSIONS: We found an additive adverse effect of psychotic episodes on
      hippocampal morphology in schizophrenia. Our findings support toxicity of
      psychosis concept, together with etiological heterogeneity of brain changes in
      schizophrenia.

PMID- 24140929
TI  - Long-term impacts of adolescent risperidone treatment on behavioral
      responsiveness to olanzapine and clozapine in adulthood.
AB  - This preclinical study investigated how a short-term risperidone treatment in
      adolescence impacts antipsychotic response to olanzapine and clozapine in
      adulthood. Antipsychotic effect was indexed by a drug's suppressive effect on
      avoidance responding in a rat conditioned avoidance response (CAR) model. Male
      adolescent Sprague-Dawley rats were first treated with risperidone (1.0mg/kg, sc)
      or sterile water and tested in the CAR model for 5 consecutive days from
      postnatal days P 40 to 44. After they became adults (~P 80-84), they were
      switched to olanzapine (0.5mg/kg, sc), clozapine (5.0mg/kg, sc) or vehicle
      treatment and tested for avoidance for 5days. During the adolescent period,
      repeated risperidone treatment produced a persistent inhibition of avoidance
      response. Throughout the 5days of adulthood drug testing, rats previously treated
      with risperidone in adolescence made significantly fewer avoidance responses than
      the vehicle ones when they all were switched to olanzapine, indicating a
      risperidone-induced enhancement of behavioral sensitivity to olanzapine. In
      contrast, when switched to clozapine, rats previously treated with risperidone
      made significantly more avoidance responses than the vehicle rats, indicating a
      risperidone-induced decrease of behavioral sensitivity to clozapine. Performance
      in the prepulse inhibition of acoustic startle response in adulthood was not
      altered by adolescent risperidone treatment. Collectively, adolescent risperidone
      exposure induced a long-term change in behavioral sensitivity to other atypical
      antipsychotic drugs, with the specific direction of change (i.e., increase or
      decrease) dependent on the drug to be switched to. These long-lasting changes are
      likely mediated by drug-induced neuroplastic changes and may also have
      significant clinical implications for antipsychotic treatment of chronic patients
      with an early onset of psychotic symptoms. 

PMID- 24140930
TI  - Serotonin transporter genotype, salivary cortisol, neuroticism and life events:
      impact on subsequent psychopathology in healthy twins at high and low risk for
      affective disorder.
AB  - OBJECTIVE: To investigate if cortisol alone or in interaction with other risk
      factors (familial risk, the serotonin transporter genotype, neuroticism and life
      events (LEs)) predicts onset of psychiatric disorder in healthy individuals at
      heritable risk. MATRIAL AND METHODS: In a high-risk study, 234 healthy
      monozygotic and dizygotic twins with or without a co-twin history of affective
      disorder (high and low risk twins) were baseline assessed. Participants were
      followed up for seven years and then reassessed with a personal interview
      revealing whether they had developed psychiatric illness. RESULTS: 36
      participants (15.4%) developed psychiatric disorder. Using Cox proportional
      hazards ratio (HR) estimates neither morning nor evening salivary cortisol at
      baseline did predict illness onset. In multivariate Cox models, the two-way
      interaction between morning cortisol and LEs lifetime before baseline was
      significantly associated with onset. Further, the HR of onset was higher
      concerning individuals carrying the short allele of the 5-HTTPLR and having
      experienced more LEs lifetime. Familial risk for affective disorder predicted
      illness and the risk of onset was further increased in individuals at familial
      risk carrying the short allele of the 5-HTTPLR. CONCLUSIONS: Cortisol levels
      alone do not increase the risk of onset of psychiatric illness but the
      interaction of a lower cortisol level and the experience of more LEs do. The 5
      HTTLPR genotype seems to interact and contribute to increased stress
      vulnerability in combination with other stress indicators of illness thereby
      adding to the risk of subsequent psychopathology.

PMID- 24140931
TI  - Antidiabetic-drug combination treatment for glucose intolerance in adult female
      rats treated acutely with olanzapine.
AB  - Second generation antipsychotic drugs are routinely used as treatment for
      psychotic disorders. Many of these compounds, including olanzapine, cause
      metabolic side-effects such as impaired glucose tolerance and insulin resistance.
      Individual antidiabetic drugs can help control elevated glucose levels in
      patients treated with antipsychotics, but the effects of combining antidiabetics,
      which routinely occurs with Type 2 diabetes mellitus patients, have never been
      studied. Presently, we compared the effects of the three different antidiabetics
      metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg,
      p.o.) on metabolic dysregulation in adult female rats treated acutely with
      olanzapine. In addition, dual combinations of each of these antidiabetics were
      compared head-to-head against each other and the individual drugs. The animals
      received two daily treatments with antidiabetics and were then treated acutely
      with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were
      measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and
      highly significant glucose intolerance compared to vehicle treated rats.
      Rosiglitazone decreased glucose levels non-significantly, while both metformin
      and glyburide significantly decreased glucose levels compared to olanzapine-only
      treated animals. For antidiabetic dual-drug combinations, the rosiglitazone
      metformin group showed an unexpected increase in glucose levels compared to all
      of the single antidiabetic drugs. However, both the metformin-glyburide and
      rosiglitazone-glyburide groups showed significantly greater reductions in glucose
      levels following olanzapine than with single drug treatment alone for metformin
      or rosiglitazone, bringing glucose levels down to values equivalent to vehicle
      only treated animals. These findings indicate that further study of antidiabetic
      dual-drug combinations in patients treated with antipsychotic drugs is warranted.

PMID- 24140932
TI  - The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo
      antitumor properties and a favorable tolerability profile.
AB  - VEGF receptor (VEGFR) signaling plays a key role in tumor angiogenesis. Although
      some VEGFR signal-targeted drugs have been approved for clinical use, their
      utility is limited by associated toxicities or resistance to such therapy. To
      overcome these limitations, we developed TAS-115, a novel VEGFR and hepatocyte
      growth factor receptor (MET)-targeted kinase inhibitor with an improved safety
      profile. TAS-115 inhibited the kinase activity of both VEGFR2 and MET and their
      signal-dependent cell growth as strongly as other known VEGFR or MET inhibitors.
      On the other hand, kinase selectivity of TAS-115 was more specific than that of
      sunitinib and TAS-115 produced relatively weak inhibition of growth (GI50 > 10
      MUmol/L) in VEGFR signal- or MET signal-independent cells. Furthermore, TAS-115
      induced less damage in various normal cells than did other VEGFR inhibitors.
      These data suggest that TAS-115 is extremely selective and specific, at least in
      vitro. In in vivo studies, TAS-115 completely suppressed the progression of MET
      inactivated tumor by blocking angiogenesis without toxicity when given every day
      for 6 weeks, even at a serum-saturating dose of TAS-115. The marked selectivity
      of TAS-115 for kinases and targeted cells was associated with improved
      tolerability and contributed to the ability to sustain treatment without dose
      reduction or a washout period. Furthermore, TAS-115 induced marked tumor
      shrinkage and prolonged survival in MET-amplified human cancer-bearing mice.
      These data suggest that TAS-115 is a unique VEGFR/MET-targeted inhibitor with
      improved antitumor efficacy and decreased toxicity.

PMID- 24140933
TI  - Crizotinib, a c-Met inhibitor, prevents metastasis in a metastatic uveal melanoma
      model.
AB  - Uveal melanoma is the most common primary intraocular malignant tumor in adults
      and half of the primary tumors will develop fatal metastatic disease to the liver
      and the lung. Crizotinib, an inhibitor of c-Met, anaplastic lymphoma kinase
      (ALK), and ROS1, inhibited the phosphorylation of the c-Met receptor but not of
      ALK or ROS1 in uveal melanoma cells and tumor tissue. Consequently, migration of
      uveal melanoma cells was suppressed in vitro at a concentration associated with
      the specific inhibition of c-Met phosphorylation. This effect on cell migration
      could be recapitulated with siRNA specific to c-Met but not to ALK or ROS1.
      Therefore, we developed a uveal melanoma metastatic mouse model with EGFP
      luciferase-labeled uveal melanoma cells transplanted by retro-orbital injections
      to test the effect of crizotinib on metastasis. In this model, there was
      development of melanoma within the eye and also metastases to the liver and lung
      at 7 weeks after the initial transplantation. When mice were treated with
      crizotinib starting 1 week after the transplantation, we observed a significant
      reduction in the development of metastases as compared with untreated control
      sets. These results indicate that the inhibition of c-Met activity alone may be
      sufficient to strongly inhibit metastasis of uveal melanoma from forming,
      suggesting crizotinib as a potential adjuvant therapy for patients with primary
      uveal melanoma who are at high risk for the development of metastatic disease.

PMID- 24140935
TI  - The atomic scale structure of CXV carbon: wide-angle x-ray scattering and
      modeling studies.
AB  - The disordered structure of commercially available CXV activated carbon produced
      from finely powdered wood-based carbon has been studied using the wide-angle x
      ray scattering technique, molecular dynamics and density functional theory
      simulations. The x-ray scattering data has been converted to the real space
      representation in the form of the pair correlation function via the Fourier
      transform. Geometry optimizations using classical molecular dynamics based on the
      reactive empirical bond order potential and density functional theory at the
      B3LYP/6-31g* level have been performed to generate nanoscale models of CXV carbon
      consistent with the experimental data. The final model of the structure comprises
      four chain-like and buckled graphitic layers containing a small percentage of
      four-fold coordinated atoms (sp(3) defects) in each layer. The presence of non
      hexagonal rings in the atomic arrangement has been also considered. 

PMID- 24140936
TI  - Fast fMRI provides high statistical power in the analysis of epileptic networks.
AB  - EEG-fMRI is a unique method to combine the high temporal resolution of EEG with
      the high spatial resolution of MRI to study generators of intrinsic brain signals
      such as sleep grapho-elements or epileptic spikes. While the standard EPI
      sequence in fMRI experiments has a temporal resolution of around 2.5-3s a newly
      established fast fMRI sequence called MREG (Magnetic-Resonance-Encephalography)
      provides a temporal resolution of around 100ms. This technical novelty promises
      to improve statistics, facilitate correction of physiological artifacts and
      improve the understanding of epileptic networks in fMRI. The present study
      compares simultaneous EEG-EPI and EEG-MREG analyzing epileptic spikes to
      determine the yield of fast MRI in the analysis of intrinsic brain signals.
      Patients with frequent interictal spikes (>3/20min) underwent EEG-MREG and EEG
      EPI (3T, 20min each, voxel size 3*3*3mm, EPI TR=2.61s, MREG TR=0.1s). Timings of
      the spikes were used in an event-related analysis to generate activation maps of
      t-statistics. (FMRISTAT, |t|>3.5, cluster size: 7 voxels, p<0.05 corrected). For
      both sequences, the amplitude and location of significant BOLD activations were
      compared with the spike topography. 13 patients were recorded and 33 different
      spike types could be analyzed. Peak T-values were significantly higher in MREG
      than in EPI (p<0.0001). Positive BOLD effects correlating with the spike
      topography were found in 8/29 spike types using the EPI and in 22/33 spikes types
      using the MREG sequence. Negative BOLD responses in the default mode network
      could be observed in 3/29 spike types with the EPI and in 19/33 with the MREG
      sequence. With the latter method, BOLD changes were observed even when few spikes
      occurred during the investigation. Simultaneous EEG-MREG thus is possible with
      good EEG quality and shows higher sensitivity in regard to the localization of
      spike-related BOLD responses than EEG-EPI. The development of new methods of
      analysis for this sequence such as modeling of physiological noise, temporal
      analysis of the BOLD signal and defining appropriate thresholds is required to
      fully profit from its high temporal resolution. 

PMID- 24140934
TI  - Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV
      associated primary effusion lymphoma.
AB  - Sphingosine kinase (SPHK) is overexpressed by a variety of cancers, and its
      phosphorylation of sphingosine results in accumulation of sphingosine-1-phosphate
      (S1P) and activation of antiapoptotic signal transduction. Existing data indicate
      a role for S1P in viral pathogenesis, but roles for SPHK and S1P in virus
      associated cancer progression have not been defined. Rare pathologic variants of
      diffuse large B-cell lymphoma arise preferentially in the setting of HIV
      infection, including primary effusion lymphoma (PEL), a highly mortal tumor
      etiologically linked to the Kaposi's sarcoma-associated herpesvirus (KSHV). We
      have found that ABC294640, a novel clinical-grade small molecule selectively
      targeting SPHK (SPHK2 >> SPHK1), induces dose-dependent caspase cleavage and
      apoptosis for KSHV(+) patient-derived PEL cells, in part through inhibition of
      constitutive signal transduction associated with PEL cell proliferation and
      survival. These results were validated with induction of PEL cell apoptosis using
      SPHK2-specific siRNA, as well as confirmation of drug-induced SPHK inhibition in
      PEL cells with dose-dependent accumulation of proapoptotic ceramides and
      reduction of intracellular S1P. Furthermore, we demonstrate that systemic
      administration of ABC294640 induces tumor regression in an established human PEL
      xenograft model. Complimentary ex vivo analyses revealed suppression of signal
      transduction and increased KSHV lytic gene expression within drug-treated tumors,
      with the latter validated in vitro through demonstration of dose-dependent viral
      lytic gene expression within PEL cells exposed to ABC294640. Collectively, these
      results implicate interrelated mechanisms and SPHK2 inhibition in the induction
      of PEL cell death by ABC294640 and rationalize evaluation of ABC294640 in
      clinical trials for the treatment of KSHV-associated lymphoma.

PMID- 24140937
TI  - Abnormal cortical thickness in heroin-dependent individuals.
AB  - Accumulating evidence from brain structural imaging studies on heroin dependence
      has supported links between brain morphological alterations and heroin exposure,
      particularly in gray matter volume or gray matter density. However, the effects
      of heroin exposure on cortical thickness and the relationship between cortical
      thickness and heroin addiction are not yet known. In this study, we acquired 3D
      high-resolution brain structural magnetic resonance imaging (MRI) data from 18
      heroin-dependent individuals (HDIs) and 15 healthy controls (HCs). Using
      FreeSurfer, we detected abnormalities in cortical thickness in the HDIs. Based on
      a vertex-wise analysis, the HDIs showed significantly decreased cortical
      thickness in the bilateral superior frontal, left caudal middle frontal, right
      superior temporal, and right insular regions compared to the HCs but
      significantly increased cortical thickness in the left superior parietal,
      bilateral lingual, left temporal pole, right inferior parietal, right lateral
      occipital, and right cuneus regions. To supplement these results, a subsequent
      ROI-wise analysis was performed and showed decreased cortical thickness in the
      left superior frontal sulcus, left precuneus gyrus, left calcarine sulcus, left
      anterior transverse collateral sulcus, and the right medial occipital-temporal
      and lingual sulcus. These regions partially overlapped with the areas identified
      using the vertex-wise analysis. In addition, we found that the thickness in the
      right superior frontal and right insular regions was negatively correlated with
      the duration of heroin use. These results provide compelling evidence for
      cortical abnormality in HDIs and also suggest that the duration of heroin use may
      be a critical factor associated with the brain alteration. 

PMID- 24140938
TI  - Mirror-neuron system recruitment by action observation: effects of focal brain
      damage on mu suppression.
AB  - Mu suppression is the attenuation of EEG power in the alpha frequency range (8-12
      Hz), recorded over the sensorimotor cortex during execution and observation of
      motor actions. Based on this dual characteristic mu suppression is thought to
      signalize activation of a human analogue of the mirror neuron system (MNS) found
      in macaque monkeys. However, much uncertainty remains concerning its specificity
      and full significance. To further explore the hypothesized relationship between
      mu suppression and MNS activation, we investigated how it is affected by damage
      to cortical regions, including areas where the MNS is thought to reside. EEG was
      recorded in 33 first-event stroke patients during observation of video clips
      showing reaching and grasping hand movements. We examined the modulation of EEG
      oscillations at central and occipital sites, and analyzed separately the lower (8
      10 Hz) and higher (10-12 Hz) segments of the alpha/mu range. Suppression was
      determined relative to observation of a non-biological movement. Normalized
      lesion data were used to investigate how damage to regions of the fronto-parietal
      cortex affects the pattern of suppression. The magnitude of mu suppression during
      action observation was significantly reduced in the affected hemisphere compared
      to the unaffected hemisphere. Differences between the hemispheres were
      significant at central (sensorimotor) sites but not at occipital (visual) sites.
      Total hemispheric volume loss did not correlate with mu suppression. Suppression
      in the lower mu range in the unaffected hemisphere (C3) correlated with lesion
      extent within the right inferior parietal cortex. Our lesion study supports the
      role of mu suppression as a marker of MNS activation, confirming previous studies
      in normal subjects.

PMID- 24140939
TI  - Bayesian networks for fMRI: a primer.
AB  - Bayesian network analysis is an attractive approach for studying the functional
      integration of brain networks, as it includes both the locations of connections
      between regions of the brain (functional connectivity) and more importantly the
      direction of the causal relationship between the regions (directed functional
      connectivity). Further, these approaches are more attractive than other
      functional connectivity analyses in that they can often operate on larger sets of
      nodes and run searches over a wide range of candidate networks. An important
      study by Smith et al. (2011) illustrated that many Bayesian network approaches
      did not perform well in identifying the directionality of connections in
      simulated single-subject data. Since then, new Bayesian network approaches have
      been developed that have overcome the failures in the Smith work. Additionally,
      an important discovery was made that shows a preprocessing step used in the Smith
      data puts some of the Bayesian network methods at a disadvantage. This work
      provides a review of Bayesian network analyses, focusing on the methods used in
      the Smith work as well as methods developed since 2011 that have improved
      estimation performance. Importantly, only approaches that have been specifically
      designed for fMRI data perform well, as they have been tailored to meet the
      challenges of fMRI data. Although this work does not suggest a single best model,
      it describes the class of models that perform best and highlights the features of
      these models that allow them to perform well on fMRI data. Specifically, methods
      that rely on non-Gaussianity to direct causal relationships in the network
      perform well. 

PMID- 24140940
TI  - Post-operative ileus in hemicolectomy for cancer: open versus laparoscopic
      approach.
AB  - AIM: This study aims to verify if the duration of postoperative ileus (POI), in
      patients undergoing abdominal surgery, is related to the surgical approach used
      (open or laparoscopic) or rather to the manipulation of bowel loops. MATERIALS
      AND METHODS: Ninety patients, undergoing elective colon resection for cancer,
      were randomized in three groups with different surgical approaches: open
      technique with extensive manipulation of intestinal loops (GROUP A), open
      technique with minimal manipulation (GROUP B) and laparoscopic technique (GROUP
      C). Return of bowel functions was investigated by: detection of bowel sounds,
      passage of flatus and passage of stool. RESULTS: Detection of bowel sounds
      occurred after 2.18 days in GROUP A, after 1.35 days in GROUP B and after 1.19
      days in GROUP C. Return of flatus occurred after 3.51 days in Group A, after 2.53
      days in GROUP B and after 2.30 days in GROUP C. Passage of stool occurred after
      4.48 days in GROUP A, after 3.75 days in GROUP B and after 3.61 days in GROUP C.
      In all end-points analyzed, differences between GROUP A and GROUP B and between
      GROUP A and GROUP C are significant (P< 0.01) whereas the differences between
      GROUP B and GROUP C are not significant (P > 0.01). CONCLUSIONS: In colon surgery
      open technique with minimal manipulation of loops obtains similar results in
      those of the laparoscopic technique, in terms of resolution of postoperative
      ileus.

PMID- 24140941
TI  - Adenosine dry powder inhalation for bronchial challenge testing, part 1: inhaler
      and formulation development and in vitro performance testing.
AB  - Dry powder administration of adenosine by use of an effective inhaler may be an
      interesting alternative to nebulisation of adenosine 5'-monophosphate in
      bronchial challenge testing, because of a shorter administration time and more
      consistent delivered fine particle dose over the entire dose range. In this
      study, we tested various powder formulations and classifier based dispersion
      principles and investigated the in vitro performance of the most promising
      formulation/classifier combination in a new test inhaler system. Spray-dried
      formulations of either pure adenosine (100%) or adenosine and lactose as diluent
      (1% and 10% adenosine) were prepared to cover the entire expected dose range for
      adenosine (0.01-20mg). All three powders, in all 12 suggested doses, dispersed
      well with the newly developed test inhaler with a multiple air jet classifier
      disperser, into aerosols with an average volume median diameter of 3.1MUm (3.0
      3.3MUm). For eleven out of 12 dose steps, the fine particle fractions<5MUm as
      percent of the loaded dose varied within the range of 67-80% (mean: 74%). The new
      test concept allows for more consistent aerosol delivery over the entire dose
      range with narrower size distributions than nebulisation and thus may improve
      adenosine administration in bronchial challenge testing. 

PMID- 24140942
TI  - Analgesic effects of dyspnoea: "Air hunger" does not inhibit the spinal
      nociception reflex in humans.
AB  - Dyspnoea has distinct sensory modalities, including air hunger and the sensation
      of excessive breathing "work/effort". Both have analgesic properties. In the case
      of work/effort, spinal mechanisms have been documented (inhibitory effect on the
      spinal nociceptive flexor reflex, RIII). This mechanism involves C-fibres. As C
      fibres are unlikely to play a major role in air hunger, we hypothesised that
      inducing this type of dyspnoea would not result in RIII inhibition. Eight healthy
      volunteers were exposed to a hypercapnic hyperoxic gas mixture (5% CO2 and 95%
      O2) and asked to voluntarily fight the corresponding ventilatory reflex response
      by reducing tidal volume below its spontaneous level. Ventilatory variables and
      dyspnoea intensity (ordinal scale) were measured. Electromyography of the biceps
      femoris was used to record the amplitude of RIII in response to painful
      electrical sural nerve stimulation. Air hunger failed to inhibit the RIII reflex.
      We conclude that the mechanisms of air hunger induced analgesia do not include a
      spinal contribution and are therefore mostly central. 

PMID- 24140943
TI  - Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung
      injury model in mice.
AB  - Our objective was to investigate the pathogenesis pathways of idiopathic
      pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental
      lung fibrosis were used. CHIP assay was executed to find the link between Smad3
      and IL-31, and the expressions of TGF-beta1, Smad3, IL-31 and STAT1 were detected
      to find whether they were similar with each other. We found that in the early
      injury or inflammation of the animal model, BLM promoted the development of
      inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF
      beta1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region,
      followed by the activation of JAK-STAT pathways. The inhibitor of TGF-beta1
      receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased
      the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM
      induced mouse model that involves the TGF-beta, IL-31 and JAKs/STATs pathway. 

PMID- 24140944
TI  - Microbial recycling of glycerol to biodiesel.
AB  - The sustainable supply of lipids is the bottleneck for current biodiesel
      production. Here microbial recycling of glycerol, byproduct of biodiesel
      production to biodiesel in engineered Escherichia coli strains was reported. The
      KC3 strain with capability of producing fatty acid ethyl esters (FAEEs) from
      glucose was used as a starting strain to optimize fermentation conditions when
      using glycerol as sole carbon source. The YL15 strain overexpressing double
      copies of atfA gene displayed 1.7-fold increase of FAEE productivity compared to
      the KC3 strain. The titer of FAEE in YL15 strain reached to 813 mg L(-1) in
      minimum medium using glycerol as sole carbon source under optimized fermentation
      conditions. The titer of glycerol-based FAEE production can be significantly
      increased by both genetic modifications and fermentation optimization. Microbial
      recycling of glycerol to biodiesel expands carbon sources for biodiesel
      production.

PMID- 24140945
TI  - Effect of trace tetracycline concentrations on the structure of a microbial
      community and the development of tetracycline resistance genes in sequencing
      batch reactors.
AB  - The objective of this study was to investigate effects of different
      concentrations of tetracycline (TC) on the microbial community and development of
      tetracycline resistance genes (TRGs) of sequencing batch reactors (SBRs).
      Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE)
      analysis of 16S rRNA and real-time fluorescence quantitative polymerase chain
      reaction (RT-qPCR) were used to detect the structural changes of the microbial
      community and the variations of eight TC resistance genes tet(A), tet(B), tet(C),
      tet(E), tet(M), tet(O), tet(S) and tet(X), respectively. The results indicated
      that, trace TC could substantially change the structure of the microbial
      community. Bacteria which could not adapt to environment with TC were gradually
      replaced by those adapting to tetracycline. Shannon's diversity index (H) and
      Simpson's index (D) reached maximum values when the concentration of TC was 1 MUg
      L(-1). The resistance genes in the activated sludge proliferated under the
      pressure of trace TC.

PMID- 24140946
TI  - Thermogravimetric study of the combustion of Tetraselmis suecica microalgae and
      its blend with a Victorian brown coal in O2/N2 and O2/CO2 atmospheres.
AB  - The combustion characteristics of microalgae, brown coal and their blends under
      O2/N2 and O2/CO2 atmospheres were studied using thermogravimetry. In microalgae
      combustion, two peaks at 265 and 485 degrees C were attributable to combustion of
      protein and carbohydrate with lipid, respectively. The DTG profile of coal showed
      one peak with maximum mass loss rate at 360 degrees C. Replacement of N2 by CO2
      delayed the combustion of coal and microalgae. The increase in O2 concentration
      did not show any effect on combustion of protein at the first stage of microalgae
      combustion. However, between 400 and 600 degrees C, with the increase of O2
      partial pressure the mass loss rate of microalgae increased and TG and DTG curves
      of brown coal combustion shifted to lower temperature zone. The lowest and
      highest activation energy values were obtained for coal and microalgae,
      respectively. With increased microalgae/coal ratio in the blends, the activation
      energy increased due to synergy effect. 

PMID- 24140947
TI  - Inhibitory effects and biotransformation potential of ciprofloxacin under
      anoxic/anaerobic conditions.
AB  - The inhibitory effects and biotransformation potential of the fluoroquinolone
      antibiotic ciprofloxacin (CIP) under anoxic (i.e., nitrate reducing) and
      anaerobic (i.e., sulfate reducing and methanogenic) conditions were investigated.
      Fermentation and sulfate reduction was inhibited in 10-80 mg/L CIP-amended
      sulfate-reducing cultures but recovered with prolonged incubation. Methanogenesis
      in the mixed culture was significantly inhibited at 80-100 mg CIP/L. No
      significant decrease of CIP concentration was observed under both sulfate
      reducing and methanogenic conditions. However, a low degree of CIP
      biotransformation was observed in a fed-batch denitrifying culture after a lag
      time even though the microbial, denitrifying activity was gradually inhibited at
      24-40 mg CIP/L. Furthermore, the degradation of CIP was accelerated with a CIP
      reamendment of the denitrifying culture. Two CIP biotransformation products in
      the denitrifying culture were detected and their proposed chemical structures
      suggest that the antibiotic quinolone moiety of CIP was intact.

PMID- 24140948
TI  - Synthesis and evaluation of the apoptosis inducing and CT DNA interaction
      properties of a series of 4beta-carbamoyl 4'-O-demethylepipodophyllotoxins.
AB  - A series of carbamate derivatives of 4'-demethylepipodophyllotoxin have been
      synthesized, and their cytotoxicities against several human cancer cell lines,
      including HeLa, A549, HCT-8, and HL-60 cells, evaluated. Some of these compounds
      exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4beta
      4'-Demethylepipodophyllotoxin 1-(4-nitrophenyl) piperazinyl carbamate (19) was
      found to be the most potent compound of those synthesized in the current study,
      and induced cell cycle arrest in the G2/M phase in HeLa cells, which was
      accompanied by apoptosis. Furthermore, this compound activated the expression of
      Bax, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of
      calf thymus DNA from the B-form to a more compact C-form. 

PMID- 24140949
TI  - Azole-carbodithioate hybrids as vaginal anti-Candida contraceptive agents:
      design, synthesis and docking studies.
AB  - Azole and carbodithioate hybrids were synthesized as alkyl 1H-azole-1
      carbodithioates (7-27) and evaluated for spermicidal/microbicidal activities
      against human sperm, Trichomonas vaginalis and Candida species. Seventeen
      compounds (7-14, 16-18 and 20-25) showed spermicidal activity at MEC 1.0% (w/v)
      and permanently immobilized 100% normal human spermatozoa within ~30 s. Seventeen
      compounds (7-11, 13-18 and 20-25) exhibited anti-Candida activity (IC50 1.26
      47.69 MUg/mL). All compounds were devoid of bactericidal activity against four
      bacterial strains (50.00 MUg/mL) and antiprotozoal activity against Trichomonas
      vaginalis (200.00 MUg/mL). Four promising compounds (10, 17, 20 and 22) have
      better safety profile as compared to Nonoxynol-9 (N-9). Docking study was done to
      visualize the possible interaction of designed scaffold with prospective receptor
      (Cyp51) of Candida albicans.

PMID- 24140950
TI  - Design, synthesis and receptor affinity of novel conformationally restricted
      sigma ligands based on the [4.3.3]propellane scaffold.
AB  - A series of novel diastereoisomeric sigma ligands 3 was designed, synthesized and
      pharmacologically evaluated. The highly rigid [4.3.3]propellane scaffold was used
      to fix the three dimensional orientation of the pharmacophoric moieties required
      for sigma affinity. The syn,syn-configured aminocarbamate syn,syn-3a reveals the
      most promising sigma1 affinity (Ki = 77 nM) and selectivity over the sigma2
      subtype (21-fold). The sigma2 affinity of all four diastereomers 3 was in the low
      micromolar range. Analysis of the distance between the hydrophobic regions
      (phenyl moieties) of the diastereomers 3 led to the longest range of distances
      (10.3-15.2 A) for the most potent sigma1 ligand syn,syn-3a, which is in good
      agreement with pharmacophore models.

PMID- 24140951
TI  - Novel polyamine analogues: from substrates towards potential inhibitors of
      monoamine oxidases.
AB  - New polyamine derivatives 1-8, related to the previously reported N(1),N(12)
      dibenzyldodecane-1,12-diamine (Bis-Bza-Diado) and N(1)-benzyl-spermine (BD6),
      have been synthesized and used as "probes" (potential substrates or inhibitors)
      of the human monoamine oxidases (MAO A and MAO B) and Vascular-Adhesion-protein 
      1 (VAP-1). Compound 8, the most effective inhibitor of the series, is
      characterized by a 12-methylene carbon chain ending with an isothiocyanate (ITC)
      group. Interestingly, it behaves as competitive inhibitor of MAO B and as
      irreversible inhibitor of MAO A. Compound 3, an asymmetric spermine analogue
      bearing a thiophene ring, acts as a reversible mixed inhibitor, selective for MAO
      B (K(IE) = 23 MUM). Docking studies performed using the available Protein Data
      Bank (PDB) structures of MAO A and MAO B, suggested that the different mode of
      inhibition of 8 may be explained by the different binding poses of 8 into the
      active site cavities of the two MAO isoforms. The epsilon-amino group of Lys 305
      of MAO A is proposed as possible target of the ITC group of the inhibitor.
      Further studies are in progress to confirm this hypothesis. These results
      indicate a potential use of the polyamine scaffold for the development of new MAO
      inhibitors for application in human pathologies involving these enzymes.

PMID- 24140952
TI  - Linking psychoanalysis with neuroscience: the concept of ego.
AB  - Through his whole life Marc Jeannerod was fascinated by Freud's thinking. His
      interest in Freud is witnessed by several of his writings in which he expresses
      interest in building a bridge between psychoanalysis and cognitive neuroscience.
      Following Jeannerod's ideas we discuss here a fundamental point of Freud's
      construction, the concept of ego, from a neurophysiological point of view. We
      maintain that, in order both to act coherently and to have a basic, first person,
      understanding of the behavior of others, it is necessary to posit the existence
      of a neurophysiological "motor" ego similar to the "rider" of the Freudian
      metaphor. We review then a series of neurophysiological findings showing that the
      systems underlying the organization of action and conscious perception are both
      mediated by a cortical motor network formed by parieto-frontal circuits. In
      conclusion, we show that the activity of this network has strong similarities to
      that postulated by Freud for the conscious part of ego. We also propose that the
      default-mode network might represent that part of ego that is mostly involved in
      unconscious processes. 

PMID- 24140953
TI  - Pathological trunk motion during walking in children with amyoplasia: is it
      caused by muscular weakness or joint contractures?
AB  - The aim was to investigate the causes for pathological trunk movements during
      gait in children with Amyoplasia. Eighteen children with Amyoplasia were compared
      with 18 typically developed children. Three-dimensional motions of pelvis, thorax
      and spine during gait were analyzed. Excessive trunk movements were defined as
      being above 4 standard deviations of those of typically developed children.
      Clinical examination of active strength and passive range of motion of the hip,
      knee and ankle joints were correlated to the parameter that showed the greatest
      prevalence of pathological trunk motion. The greatest prevalence of 56% was seen
      for thorax obliquity range during walking. The spine angles showed the lowest
      deviations from typically developed children. Significant correlations (p<0.001)
      between thorax obliquity range and clinical parameters were found for passive hip
      extension, hip flexion, hip abduction and active hip extension, hip flexion and
      ankle dorsiflexion strength. The highest correlation coefficients were found for
      passive hip flexion and active hip flexion strength of rho=-0.73 and rho=-0.69
      respectively. Excessive thorax obliquity during gait in children with Amyoplasia
      could be mainly caused by reduced strength and mobility of the hip. Therefore
      both mobility and strength of the hip are equally important and should be
      increased in the therapy to improve gait in children with Amyoplasia. 

PMID- 24140954
TI  - Cone beam CT imaging with limited angle of projections and prior knowledge for
      volumetric verification of non-coplanar beam radiation therapy: a proof of
      concept study.
AB  - Non-coplanar beams are important for treatment of both cranial and noncranial
      tumors. Treatment verification of such beams with couch rotation/kicks, however,
      is challenging, particularly for the application of cone beam CT (CBCT). In this
      situation, only limited and unconventional imaging angles are feasible to avoid
      collision between the gantry, couch, patient, and on-board imaging system. The
      purpose of this work is to develop a CBCT verification strategy for patients
      undergoing non-coplanar radiation therapy. We propose an image reconstruction
      scheme that integrates a prior image constrained compressed sensing (PICCS)
      technique with image registration. Planning CT or CBCT acquired at the neutral
      position is rotated and translated according to the nominal couch
      rotation/translation to serve as the initial prior image. Here, the nominal couch
      movement is chosen to have a rotational error of 5 degrees  and translational
      error of 8 mm from the ground truth in one or more axes or directions. The
      proposed reconstruction scheme alternates between two major steps. First, an
      image is reconstructed using the PICCS technique implemented with total-variation
      minimization and simultaneous algebraic reconstruction. Second, the
      rotational/translational setup errors are corrected and the prior image is
      updated by applying rigid image registration between the reconstructed image and
      the previous prior image. The PICCS algorithm and rigid image registration are
      alternated iteratively until the registration results fall below a predetermined
      threshold. The proposed reconstruction algorithm is evaluated with an
      anthropomorphic digital phantom and physical head phantom. The proposed algorithm
      provides useful volumetric images for patient setup using projections with an
      angular range as small as 60 degrees . It reduced the translational setup errors
      from 8 mm to generally <1 mm and the rotational setup errors from 5 degrees  to
      <1 degrees . Compared with the PICCS algorithm alone, the integration of rigid
      registration significantly improved the reconstructed image quality, with a
      reduction of mostly 2-3 folds (up to 100) in root mean square image error. The
      proposed algorithm provides a remedy for solving the problem of non-coplanar CBCT
      reconstruction from limited angle of projections by combining the PICCS technique
      and rigid image registration in an iterative framework. In this proof of concept
      study, non-coplanar beams with couch rotations of 45 degrees  can be effectively
      verified with the CBCT technique. 

PMID- 24140955
TI  - RMCgui: a new interface for the workflow associated with running Reverse Monte
      Carlo simulations.
AB  - The Reverse Monte Carlo method enables construction and refinement of large
      atomic models of materials that are tuned to give best agreement with
      experimental data such as neutron and x-ray total scattering data, capturing both
      the average structure and fluctuations. The practical drawback with the current
      implementations of this approach is the relatively complex workflow required,
      from setting up the configuration and simulation details through to checking the
      final outputs and analysing the resultant configurations. In order to make this
      workflow more accessible to users, we have developed an end-to-end workflow
      wrapped within a graphical user interface-RMCgui-designed to make the Reverse
      Monte Carlo more widely accessible. 

PMID- 24140956
TI  - Exploring unsymmetrical dyads as efficient inhibitors against the insect beta-N
      acetyl-D-hexosaminidase OfHex2.
AB  - The GH20 beta-N-acetyl-d-hexosaminidase OfHex2 from the insect Ostrinia
      furnacalis (Guenee) is a target potential for eco-friendly pesticide development.
      Although carbohydrate-based inhibitors against beta-N-acetyl-D-hexosaminidases
      are widely studied, highly efficient, non-carbohydrate inhibitors are more
      attractive due to low cost and readily synthetic manner. Based on molecular
      modeling analysis of the catalytic domain of OfHex2, a series of novel
      naphthalimide-scaffold conjugated with a small aromatic moiety by an alkylamine
      spacer linker were designed and evaluated as efficiently competitive inhibitors
      against OfHex2. The most potent one containing naphthalimide and phenyl groups
      spanning by an N-alkylamine linker has a Ki value of 0.37 MUM, which is 6 fold
      lower than that of M-31850, the most potent non-carbohydrate inhibitor ever
      reported. The straightforward synthetic manners as well as the presumed binding
      model in this paper could be advantageous for further structural optimization for
      developing inhibitors against GH20 beta-N-acetyl-D-hexosaminidases.

PMID- 24140957
TI  - Structural basis for the rational design of new anti-Brucella agents: the crystal
      structure of the C366S mutant of L-histidinol dehydrogenase from Brucella suis.
AB  - L-Histidinol dehydrogenase from Brucella suis (BsHDH) is an enzyme involved in
      the histidine biosynthesis pathway which is absent in mammals, thus representing
      a very interesting target for the development of anti-Brucella agents. In this
      paper we report the crystallographic structure of a mutated form of BsHDH both in
      its unbound form and in complex with a nanomolar inhibitor. These studies provide
      the first structural background for the rational design of potent HDH inhibitors,
      thus offering new hints for clinical applications.

PMID- 24140958
TI  - Biochemical analysis of a rhodopsin photoactivatable GFP fusion as a model of G
      protein coupled receptor transport.
AB  - Rhodopsin is trafficked to the rod outer segment of vertebrate rod cells with
      high fidelity. When rhodopsin transport is disrupted retinal photoreceptors
      apoptose, resulting in the blinding disease autosomal dominant retinitis
      pigmentosa. Herein, we introduce rhodopsin-photoactivatable GFP-1D4 (rhodopsin
      paGFP-1D4) for the purposes of monitoring rhodopsin transport in living cells.
      Rhodopsin-paGFP-1D4 contains photoactivatable GFP (paGFP) fused to rhodopsin's C
      terminus and the last eight amino acids of rhodopsin (1D4) appended to the C
      terminus of paGFP. The fusion protein binds the chromophore 11-cis retinal and
      photoisomerizes upon light activation similarly to rhodopsin. It activates the G
      protein transducin with similar kinetics as does rhodopsin. Rhodopsin-paGFP-1D4
      localizes to the same compartments, the primary cilium in cultured IMCD cells and
      the outer segment of rod cells, as rhodopsin in vitro and in vivo. This enables
      its use as a model of rhodopsin transport and details the importance of a free
      rhodopsin C-terminus in rod cell localization and health. 

PMID- 24140959
TI  - Patients with schizophrenia show deficits on spatial frequency doubling.
AB  - There are pieces of evidence indicating that visual deficits in patients with
      schizophrenia can be attributed to a deficiency in the magnocellular portion of
      the early visual system. The main objective of this study was to investigate the
      neurological dysfunction of the magnocellular pathway in patients with
      schizophrenia using the frequency doubling technology perimetry (FDT). The FDT
      has been developed based on particular neural magnocellular characteristics and
      can examine the magnocellular dysfunction hypothesis in schizophrenia. Twenty
      patients with schizophrenia (12 males and 8 females) and 20 normal subjects (10
      males and 10 females) participated in this study. The spatial frequency doubling
      task was presented via the Humphrey perimetry instrument in order to examine the
      magnocellular pathway of the participants. Patients with schizophrenia showed
      less visual field sensitivity than normal controls and their standardized age
      cohort in both eyes (p<0.001). The results indicated impaired visual field
      sensitivity deficits in patients with schizophrenia that can be attributed to a
      deficit in the magnocellular neural pathways. This Magnocellular pathway defect
      may provide a physiological base to explain some of the deficits caused by
      schizophrenia such as cognitive deficits. 

PMID- 24140960
TI  - The effect of sleep in perceptual learning with complex objects.
AB  - Recognition of objects improves with training, but task performance also improves
      between sessions without further training. This offline learning seems to be
      influenced by post-training sleep, as is evidenced in perceptual learning studies
      with simple stimuli. In this study we aim to investigate the role of sleep in
      perceptual learning with complex natural and man-made objects. Participants were
      trained with a backward masking task during four sessions with 12h between each
      training session (morning-evening-morning-evening or evening-morning-evening
      morning). A larger improvement on performance was found after a night's sleep,
      than when subjects performed the task without having slept between training
      sessions. This effect was not influenced by the participants' chronotype or non
      verbal intelligence. In addition, we replicated some key characteristics of
      perceptual learning with complex objects. Participants were retested six days
      after the last training session with the previously trained stimulus and new
      stimuli. The performance gains were long-lasting and specific to the trained
      stimulus set. 

PMID- 24140962
TI  - Best case series program: submission of unconventional therapies from India.

PMID- 24140963
TI  - Response.

PMID- 24140965
TI  - Local structure correlations in plastic cyclohexane--a reverse Monte Carlo study.
AB  - Two solid phases of cyclohexane have been investigated over a temperature range
      spanning 13-266 K on a powdered, perdeuterated sample using neutron total
      scattering. Phase II has an ordered structure (C2/c) that forms below 186 K.
      Between 186 and 280 K it exists as a plastic solid-phase I (Fm3m), where the
      molecules are rotationally disordered about the lattice points of the face
      centred cubic cell. Data-dependent atomistic configurations that represent the
      'instantaneous' crystal structure have been generated from the total scattering
      data using reverse Monte Carlo refinement. Analysis of the local structure
      reveals that instantaneous distortions in phase I resemble the average structure
      of phase II.

PMID- 24140964
TI  - Japanese encephalitis virus infection modulates the expression of suppressors of
      cytokine signaling (SOCS) in macrophages: implications for the hosts' innate
      immune response.
AB  - Viruses have evolved various mechanisms to subvert the host's immune system and
      one of them is preventing the infected cells from sending out chemotactic signals
      to activate the adaptive immune response. Japanese encephalitis virus (JEV) is a
      neuropathologic flavivirus that is responsible for significant number of child
      mortalities in various parts of South-East Asia. In this study we show that JEV
      modulates suppressors of cytokine signaling (SOCS)1 and 3 expression in
      macrophages to bring about changes in the JAK-STAT signaling cascade, so as to
      inhibit proinflammatory cyto/chemokine release. Using real time PCR,
      immunoblotting and immunofluorescent staining, we show that the expression of
      type 1 interferons and intracellular expression of viral genes are also affected
      over time. Also, following the initial activation of SOCS1 and 3, there is
      production of interferon-inducible anti-viral proteins in the cells which may be
      responsible for inhibiting viral replication. However, even at later time points,
      viral genes were still detected from the macrophages, albeit at lesser
      quantities, than earlier time points, indicative of intracellular persistence of
      the virus in a latent form. On knocking down SOCS1 and SOCS3 we found a
      significant decrease in viral gene expression at an early time point, indicating
      the dysregulation of the signaling cascade leading to increased production of
      interferon-inducible anti-viral proteins. Taken together, our study provides an
      insight into the role of JEV infection in modulating the JAK-STAT pathway with
      the help of SOCS leading to the generation of an antiviral innate immune
      response. 

PMID- 24140966
TI  - Genotoxic evaluation of aspirin eugenol ester using the Ames test and the mouse
      bone marrow micronucleus assay.
AB  - Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of
      inflammation, pain and fever and prevention of cardiovascular diseases with less
      side effects and it is important to characterize its genotoxicity. In this study,
      the genotoxicity of AEE was assessed with two standard genotoxicity assays of the
      Salmonella typhimurium mutagenicity assay (Ames test) and the mouse bone marrow
      micronucleus assay. In the Ames test, Salmonella strains TA97, TA98, TA100, TA102
      and TA1535 were treated with or without the metabolic activation with a S9
      fraction from Acroclor-induced rat liver. The doses of AEE were 5 mg/plate, 2.5
      mg/plate, 1.25 mg/plate, 0.625 mg/plate and 0.3125 mg/plate, respectively. In the
      above tested strains, mutagenicity with or without the S-9 mixture was not
      detected. In the mammalian erythrocyte micronucleus assay, fifty mice were
      divided into five groups evenly and the AEE dose at 5000 mg/kg, 2500 mg/kg and
      1250 mg/kg and the cyclophosphamide dose at 40 mg/kg as a positive control, the
      0.5% of CMC-Na as negative control were administered. The results showed that AEE
      did not induce any significant increase in micronucleated erythrocytes after 24 h
      (p<0.01). Our results suggested that AEE was non-genotoxic in vivo or in vitro.

PMID- 24140967
TI  - The ER stress-mediated decrease in DDAH1 expression is involved in formaldehyde
      induced apoptosis in lung epithelial cells.
AB  - Formaldehyde (FA) is toxic to the respiratory system, and nitric oxide (NO)
      dysfunction stimulates the onset of respiratory diseases. The involvement of
      dimethylarginine dimethylaminohydrolase (DDAH), the l-arginine analogue
      asymmetric dimethylarginine (ADMA) degrading enzyme, in FA-induced cell death in
      lung epithelial cells has not been investigated. In this study, we assessed the
      effect of FA on DDAH expression and endoplasmic reticulum (ER) stress in A549
      cells. We also investigated the preventive effect of DDAH overexpression on ER
      stress and apoptosis in FA-induced cell death. FA decreased viability in A549
      cells and decreased DDAH1 and DDAH2 mRNA and protein expression in a time
      dependent manner (>4h). This coincided with increased phosphorylation of the ER
      stress proteins IRE1alpha, PERK, and eIF-2alpha, as well as increased expression
      of pro-apoptotic proteins such as Bax, C/EPB homologous protein (CHOP), cleaved
      PARP, and cleaved caspase-3, but decreased expression of the anti-apoptotic
      protein Bcl-2. ADMA treatment mimicked the effect of FA. Overexpression of DDAH1,
      but not DDAH2, prevented FA-induced decreases in cell viability, phosphorylation
      of IRE1alpha, PERK, and eIF2alpha, and expression of CHOP. Effects of DDAH1
      overexpression, but not DDAH2 overexpression, restored FA-induced increases in
      Bax, CHOP, cleaved PARP, cleaved caspase-3 and decreases in Bcl-2. In conclusion,
      FA induces apoptosis of lung epithelial cells via a decrease of DDAH1 through ER
      stress. 

PMID- 24140968
TI  - Effect of a glycoprotein from mushroom Hypsizygus marmoreus (Peck) Bigelow on
      growth and differentiation of human leukemic U937 cells.
AB  - A non-lectin glycoprotein (HM-3A) isolated from the basidioma of edible mushroom
      Hypsizygus marmoreus (Peck) Bigelow was shown to be inhibitory against the growth
      of human myeloid leukemia U937 cells in our previous research. The present study
      further investigated the mechanisms of inhibition and differentiation in an
      indirect model. Human mononuclear cells (MNC) were stimulated by HM-3A for 1, 2
      and 3days to obtain the conditioned media (MNC-CM1, 2 and 3) that was effective
      in inhibiting the growth of U937 cells. The percentage of mature
      monocytes/macrophages among the cells and the total productivity of superoxide
      increased in the treatment and proved the differentiation-inducing effect of HM
      3A-MNC-CM. The secretion of cytokines TNF-alpha, IL-2 and IFN-gamma from the
      treated MNC were increased. Antibody neutralization tests of HM-3A-MNC-CM1
      further showed that the growth inhibition effect of HM-3A can be attributed to
      the promotion in secretion of cytokines IFN-gamma and TNF-alpha. We propose that
      HM-3A may stimulate human MNC to secrete cytokines IFN-gamma and TNF-alpha to
      inhibit the growth of U937 cells, and that HM-3A may be developed into an anti
      leukemia ingredient in health food. 

PMID- 24140969
TI  - Probabilistic risk assessment of exposure to leucomalachite green residues from
      fish products.
AB  - To assess the potential risk of human exposure to carcinogenic leucomalachite
      green (LMG) due to fish consumption, the probabilistic risk assessment was
      conducted for adolescent, adult and senior adult consumers in Taiwan. The
      residues of LMG with the mean concentration of 13.378+/-20.56 MUg kg(-1) (BFDA,
      2009) in fish was converted into dose, considering fish intake reported for three
      consumer groups by NAHSIT (1993-1996) and body weight of an average individual of
      the group. The lifetime average and high 95th percentile dietary intakes of LMG
      from fish consumption for Taiwanese consumers were estimated at up to 0.0135 and
      0.0451 MUg kg-bw(-1) day(-1), respectively. Human equivalent dose (HED) of 2.875
      mg kg-bw(-1) day(-1) obtained from a lower-bound benchmark dose (BMDL10) in mice
      by interspecies extrapolation was linearly extrapolated to oral cancer slope
      factor (CSF) of 0.035 (mgkg-bw(-1)day(-1))(-1) for humans. Although, the
      assumptions and methods are different, the results of lifetime cancer risk
      varying from 3*10(-7) to 1.6*10(-6) were comparable to those of margin of
      exposures (MOEs) varying from 410,000 to 4,800,000. In conclusions, Taiwanese
      fish consumers with the 95th percentile LADD of LMG have greater risk of liver
      cancer and need to an action of risk management in Taiwan.

PMID- 24140970
TI  - DHA sensitizes FaO cells to tert-BHP-induced oxidative effects. Protective role
      of EGCG.
AB  - The excessive production of reactive oxygen species has been implicated in
      several pathologies, such as atherosclerosis, obesity, hypertension and insulin
      resistance. Docosahexaenoic acid (DHA) may protect against the above mentioned
      diseases, but paradoxically the main DHA treated pathologies are also associated
      with increased ROS levels. Therefore, the aim of this study was to explore if in
      vitro DHA supplementation may increase the sensitivity of cells to tert-BHP
      induced oxidative stress, and if the green tea polyphenol epigallocatechin-3
      gallate (EGCG) is able to correct such detrimental effect. We found that DHA
      enriched cells exacerbate ROS generation, decrease cell viability and increase
      Nrf2 nuclear translocation and HO-1 expression. Interestingly, cellular EGCG is
      able to counteract oxidative damage from either tert-BHP or DHA-enriched cells.
      In consequence, our results suggest that in a ROS enriched environment DHA could
      not always be beneficial for cells and can be considered a double-edged sword in
      terms of its benefits vs. risks. In this sense, our results propose that the
      supplementation with potent antioxidant molecules could be an appropriate
      strategy to reduce the risks related with the DHA supplementation in an oxidative
      stress-associated condition. 

PMID- 24140971
TI  - Modeling the impact of interventions along the HIV continuum of care in Newark,
      New Jersey.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) epidemic in Newark, New
      Jersey, is among the most severe in the United States. Prevalence ranges up to
      3.3% in some groups. The aim of this study is to use a mathematical model of the
      epidemic in Newark to assess the impact of interventions along the continuum of
      care, leading to virologic suppression. METHODS: A model was constructed of HIV
      infection including specific care-continuum steps. The model was calibrated to
      HIV/AIDS cases in Newark among different populations over a 10-year period.
      Interventions applied to model fits were increasing proportions tested, linked
      and retained in care, linked and adherent to treatment, and increasing testing
      frequency, high-risk-group testing, and adherence. Impacts were assessed by
      measuring incidence and death reductions 10 years postintervention. RESULTS: The
      most effective interventions for reducing incidence were improving treatment
      adherence and increasing testing frequency and coverage. No single intervention
      reduced incidence in 2023 by >5%, and the most effective combination of
      interventions reduced incidence by approximately 16% (2%-24%). The most
      efficacious interventions for reducing deaths were increasing retention, linkage
      to care, testing coverage, and adherence. Increasing retention reduced deaths by
      approximately 27% (24%-29%); the most efficacious combination of interventions
      reduced deaths in 2023 by approximately 52% (46%-57%). CONCLUSIONS: Reducing HIV
      deaths in Newark over a 10-year period may be a realizable goal, but reducing
      incidence is less likely. Our results highlight the importance of addressing
      leaks across the entire continuum of care and reinforcing efforts to prevention
      new HIV infections with additional interventions.

PMID- 24140972
TI  - Nephrotoxicity of different formulations of amphotericin B: summarizing evidence
      by network meta-analysis.

PMID- 24140973
TI  - Reply to Messori et al.

PMID- 24140974
TI  - Protein arrays as tool for studies at the host-pathogen interface.
AB  - Pathogens and parasites encode a wide spectrum of multifunctional proteins
      interacting to and modifying proteins in host cells. However, the current lack of
      a reliable method to unveil the protein-protein interactions (PPI) at the host
      pathogen interface is retarding our understanding of many important pathogenic
      processes. Thus, the identification of proteins involved in host-pathogen
      interactions is important for the elucidation of virulence determinants,
      mechanisms of infection, host susceptibility and/or disease resistance. In this
      sense, proteomic technologies have experienced major improvements in recent years
      and protein arrays are a powerful and modern method for studying PPI in a high
      throughput format. This review focuses on these techniques analyzing the state-of
      the-art of proteomic technologies and their possibilities to diagnose and explore
      host-pathogen interactions. Major technical advancements, applications and
      protocol concerns are presented, so readers can appreciate the immense progress
      achieved and the current technical options available for studying the host
      pathogen interface. Finally, future uses of this kind of array-based proteomic
      tools in the fight against infectious and parasitic diseases are discussed. 

PMID- 24140975
TI  - A novel angiotensin converting enzyme inhibitory peptide derived from proteolytic
      digest of Chinese soft-shelled turtle egg white proteins.
AB  - In this study, soft-shelled turtle (Pelodiscus sinensis) egg white (SSTEW)
      proteins were digested by thermolysin and the resulting small peptides were
      further fractionated by reverse phase chromatography. Peptides with angiotensin I
      converting enzyme inhibitory (ACEI) activity from these fractions were screened.
      A lysozyme-derived peptide, IW-11, from the fraction with the most effective ACEI
      was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and
      its purified form showed effective ACEI activity in vitro (IC50=4.39+/-0.31MUM).
      The Lineweaver-Burk plots indicated that the inhibition towards ACE caused by
      this peptide is a competitive inhibition. The molecular docking study further
      revealed that the ACEI activity of IW-11 is mainly attributed to the formation of
      hydrogen bonds between the N-terminal residue of IW-11 and the S1 pocket (Ala354
      and Tyr523) and the S2' region (His513 and His353) of ACE. Moreover, the
      digestion parameters were further optimized and the target peptide (82% purity)
      was readily obtained (15% yield) without any cumbersome purification procedure.
      Notably, lysozyme C is the most abundant protein in SSTEW, which implies that an
      efficient production of this ACEI peptide from SSTEW is promising. BIOLOGICAL
      SIGNIFICANCE: Inhibition of ACE has proven to be an effective strategy in
      prevention and treatment of hypertension and related diseases. Unlike typical
      synthetic ACE inhibitors which exert well described side effects, food-derived
      peptides with ACE inhibitory activity may be safer alternatives for hypertension
      treatment. In this study, we comprehensively identified peptides derived from
      SSTEW digest using a proteomic approach. IW-11, which is derived from lysozyme,
      the most abundant protein in SSTEW, showed remarkable inhibition towards ACE.
      This peptide has been demonstrated to have a competitive inhibitory property
      which is able to bind to ACE active site and found to be a true inhibitor against
      ACE according to Lineweaver-Burk plots. Using an optimized thermolysin condition,
      IW-11 can be readily obtained without any complex purification step, which will
      benefit its further application to prevention or treatment of hypertension.

PMID- 24140976
TI  - Malaria proteomics: insights into the parasite-host interactions in the
      pathogenic space.
AB  - Proteomics is improving malaria research by providing global information on
      relevant protein sets from the parasite and the host in connection with its
      cellular structures and specific functions. In the last decade, reports have
      described biologically significant elements in the proteome of Plasmodium, which
      are selectively targeted and quantified, allowing for sensitive and high
      throughput comparisons. The identification of molecules by which the parasite and
      the host react during the malaria infection is crucial to the understanding of
      the underlying pathogenic mechanisms. Hence, proteomics is playing a major role
      by defining the elements within the pathogenic space between both organisms that
      change across the parasite life cycle in association with the host transformation
      and response. Proteomics has identified post-translational modifications in the
      parasite and the host that are discussed in terms of functional interactions in
      malaria parasitism. Furthermore, the contribution of proteomics to the
      investigation of immunogens for potential vaccine candidates is summarized. The
      malaria-specific technological advances in proteomics are particularly suited now
      for identifying host-parasite interactions that could lead to promising targets
      for therapy, diagnosis or prevention. In this review, we examine the knowledge
      gained on the biology, pathogenesis, immunity and diagnosis of Plasmodium
      infection from recent proteomic studies. This article is part of a Special Issue
      entitled: Trends in Microbial Proteomics. 

PMID- 24140977
TI  - Calcium signaling-related proteins are associated with broncho-pulmonary
      dysplasia progression.
AB  - Broncho-pulmonary dysplasia (BPD) is a chronic pulmonary disorder that follows
      premature birth. It is preceded by respiratory distress syndrome (RDS),
      characterized by acute respiratory failure due to deficiency of surfactant at
      birth. Clinical characteristics of infants affected by BPD have widely changed in
      the last decades: they are extraordinarly immature, with impaired alveolar and
      vascular lung development. To build up new therapeutic strategies for BPD babies,
      it is necessary to understand the pathogenic mechanisms, which are complicated by
      environmental risk factors and genetic predisposition. Therefore, the aim of this
      study was to highlight protein changes in the broncho-alveolar lavage fluid
      (BALF), thus providing an appropriate picture on what is happening in the locus
      of injury. We analyzed BALF samples from preterm babies, born at different stages
      of lung development. We confirmed that gestational age is relevant for BPD
      progression, but we also detected few de-regulated proteins in the younger
      babies; we discovered less abundant calcium signaling-related proteins,
      consistent with BPD severity, comparing severe to mild BPD babies with matched
      gestational age. In conclusion, this study suggests a subset of proteins to be
      investigated to better treat BPD babies and facilitate the definition of
      potential drug targets for novel therapies. BIOLOGICAL SIGNIFICANCE: Pulmonary
      biomarkers are needed to predict the clinical course of lung disease, status,
      progression and response to treatment. A key aspect in biomarker discovery is
      uncovering molecules that appear early during disease initiation, when the
      natural history of the disease can be modified. Using a proteomic-based approach
      we compared broncho-alveolar lavage fluid (BALF) protein profile from preterm
      neonates at different postmenstrual ages, to have a molecular description of
      broncho-pulmonary dysplasia (BPD) progression. BALF provided a snapshot of local
      molecular changes, which are relevant for early diagnosis, assessment and
      characterization of lung disorders. We showed that even if the studied patients
      had similar clinical phenotype (they all developed severe BPD and they were all
      cured in the same way in terms of mechanical ventilation, surfactant
      administration, antenatal steroid treatment and ibuprofen treatment for patent
      ductus arteriosus), however their BALF protein profiling displayed significant
      differences in a subset of proteins, which could be exploited to facilitate the
      development of novel effective therapies, distinct for age and severity of the
      disease.

PMID- 24140978
TI  - Three-gene based phylogeny of the Urostyloidea (Protista, Ciliophora,
      Hypotricha), with notes on classification of some core taxa.
AB  - Classifications of the Urostyloidea were mainly based on morphology and
      morphogenesis. Since molecular phylogeny largely focused on limited sampling
      using mostly the one-gene information, the incongruence between morphological
      data and gene sequences have risen. In this work, the three-gene data (SSU-rDNA,
      ITS1-5.8S-ITS2 and LSU-rDNA) comprising 12 genera in the "core urostyloids" are
      sequenced, and the phylogenies based on these different markers are compared
      using maximum-likelihood and Bayesian algorithms and tested by unconstrained and
      constrained analyses. The molecular phylogeny supports the following conclusions:
      (1) the monophyly of the core group of Urostyloidea is well supported while the
      whole Urostyloidea is not monophyletic; (2) Thigmokeronopsis and Apokeronopsis
      are clearly separated from the pseudokeronopsids in analyses of all three gene
      markers, supporting their exclusion from the Pseudokeronopsidae and the inclusion
      in the Urostylidae; (3) Diaxonella and Apobakuella should be assigned to the
      Urostylidae; (4) Bergeriella, Monocoronella and Neourostylopsis flavicana share a
      most recent common ancestor; (5) all molecular trees support the transfer of
      Metaurostylopsis flavicana to the recently proposed genus Neourostylopsis; (6)
      all molecular phylogenies fail to separate the morphologically well-defined
      genera Uroleptopsis and Pseudokeronopsis; and (7) Arcuseries gen. nov. containing
      three distinctly deviating Anteholosticha species is established. 

PMID- 24140979
TI  - Evolutionary diversification and speciation in rodents of the Mexican lowlands:
      the Peromyscus melanophrys species group.
AB  - Despite some studies of the species groups within the genus Peromyscus have been
      performed, both evolutionary relationships among species within groups and group
      composition have remained controversial. In this study, we address phylogenetic
      relationships among species in the Peromyscus melanophrys group (P. melanophrys,
      P. perfulvus, and P. mekisturus), using a molecular phylogenetic analysis. This
      analysis is the first to include the poorly known P. mekisturus. We conducted
      maximum likelihood and Bayesian inference analyses with the ND3, tRNA-Arginine,
      ND4L, and partial ND4 mitochondrial genes, and the GHR nuclear gene. We
      consistently recovered a P. melanophrys group that is monophyletic with respect
      to the set of outgroups. Also, we recovered two distinct clades within P.
      perfulvus and two within P. melanophrys, one of which contain P. mekisturus among
      other P. melanophrys, all with geographic consistency. According to our
      divergence time estimates, the P. melanophrys group diverged during the Pliocene
      and the main diversification events within the group occurred at the end of the
      Pliocene and through the Pleistocene. 

PMID- 24140980
TI  - Phylogenetic relationships within Bothrops neuwiedi group (Serpentes, Squamata):
      geographically highly-structured lineages, evidence of introgressive
      hybridization and Neogene/Quaternary diversification.
AB  - Eight current species of snakes of the Bothrops neuwiedi group are widespread in
      South American open biomes from northeastern Brazil to southeastern Argentina. In
      this paper, 140 samples from 93 different localities were used to investigate
      species boundaries and to provide a hypothesis of phylogenetic relationships
      among the members of this group based on 1122bp of cyt b and ND4 from
      mitochondrial DNA and also investigate the patterns and processes occurring in
      the evolutionary history of the group. Combined data recovered the B. neuwiedi
      group as a highly supported monophyletic group in maximum parsimony, maximum
      likelihood and Bayesian analyses, as well as four major clades (Northeast I,
      Northeast II, East-West, West-South) highly-structured geographically. Monophyly
      was recovered only for B. pubescens. By contrast, B. diporus, B. lutzi, B.
      erythromelas, B. mattogrossensis, B. neuwiedi, B. marmoratus, and B. pauloensis,
      as currently defined on the basis of morphology, were polyphyletic. Sympatry,
      phenotypic intergrades and shared mtDNA haplotypes, mainly between B. marmoratus
      and B. pauloensis suggest recent introgressive hybridization and the possible
      occurrence of a narrow hybrid zone in Central Brazil. Our data suggest at least
      three candidate species: B. neuwiedi from Espinhaco Range, B. mattogrossensis
      (TM173) from Serra da Borda (MT) and B. diporus (PT3404) from Castro Barros,
      Argentina. Divergence estimates highlight the importance of Neogene events in the
      origin of B. neuwiedi group, and the origin of species and diversification of
      populations of the Neotropical fauna from open biomes during the Quaternary
      climate fluctuations. Data reported here represent a remarkable increase of the
      B. neuwiedi group sampling size, since representatives of all the current
      recognized species from a wide geographic range are included in this study,
      providing basic information for understanding the evolution and conservation of
      Neotropical biodiversity. 

PMID- 24140981
TI  - Model-based evaluation of the use of polycyclic aromatic hydrocarbons molecular
      diagnostic ratios as a source identification tool.
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) molecular diagnostic ratios (MDRs) are
      unitless concentration ratios of pair-PAHs with the same molecular weight (MW);
      MDRs have long been used as a tool for PAHs source identification purposes. In
      the present paper, the efficiency of the MDR methodology is evaluated through the
      use of a multimedia fate model, the calculation of characteristic travel
      distances (CTD) and the estimation of air concentrations for individual PAHs as a
      function of distance from an initial point source. The results show that PAHs
      with the same MW are sometimes characterized by substantially different CTDs and
      therefore their air concentrations and hence MDRs are predicted to change as the
      distance from the original source increases. From the assessed pair-PAHs, the
      biggest CTD difference is seen for Fluoranthene (107 km) vs. Pyrene (26 km). This
      study provides a strong indication that MDRs are of limited use as a source
      identification tool. 

PMID- 24140982
TI  - Human mesenchymal stem cells generate a distinct pericellular zone of MMP
      activities via binding of MMPs and secretion of high levels of TIMPs.
AB  - Mesenchymal stem cells (MSCs) are attractive candidates for inclusion in cell
      based therapies by virtue of their abilities to home to wound sites. However, in
      depth characterization of the specific effects of MSCs on their microenvironments
      is needed to realize their full therapeutic potentials. Furthermore, since MSCs
      of varying properties can be isolated from a diverse spectrum of tissues, a
      strategic and rational approach in MSC sourcing for a particular application has
      yet to be achieved. For example, MSCs that activate their proteolytic
      environments may promote tissue remodeling, while those from different tissue
      sources may inhibit proteases and promote tissue stabilization. This study
      attempts to address these issues by analyzing MSCs isolated from three adult
      tissue sources in terms of their effects on their proteolytic microenvironments.
      Human bone marrow, adipose, and traumatized muscle derived MSCs were compared in
      their soluble and cellular-associated MMP components and activity. For all types
      of MSCs, MMP activity associated with the cell surface, but activity levels and
      MMP profiles differed with tissue source. All MSC types bound exogenous active
      MMPs at their surfaces. MSCs were also able to activate exogenous proMMP-2 and
      proMMP-13. This is in marked contrast to the MSC soluble compartment, which
      strongly inhibited MMPs via endogenous TIMPs. The exact TIMP used to inhibit the
      exogenous MMP differed with MSC type. Thus, MSCs saturate their environment with
      both MMPs and TIMPs. Since they bind and activate MMPs at their surfaces, the net
      result is a very controlled pericellular localization of MMP activities by MSCs. 

PMID- 24140983
TI  - Investigating end-to-end accuracy of image guided radiation treatment delivery
      using a micro-irradiator.
AB  - There is significant interest in delivering precisely targeted small-volume
      radiation treatments, in the pre-clinical setting, to study dose-volume
      relationships with tumour control and normal tissue damage. For these studies it
      is vital that image guidance systems and target positioning are accurately
      aligned (IGRT), in order to deliver dose precisely and accurately according to
      the treatment plan. In this work we investigate the IGRT targeting accuracy of
      the X-RAD 225 Cx system from Precision X-Ray using high-resolution 3D dosimetry
      techniques. Small cylindrical PRESAGE(r) dosimeters were used with optical-CT
      readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone
      attachments. The dosimeters were equipped with four target points, visible on
      both CBCT and optical-CT, at which a 7-field coplanar treatment plan was
      delivered with the respective cone. Targeting accuracy (distance to agreement
      between the target point and delivery isocenter) and cone alignment (isocenter
      precision under gantry rotation) were measured using the optical-CT images.
      Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant
      targeting error of 2.1 +/- 0.6 mm and a cone misalignment of 1.3 +/- 0.1 mm.
      After the IGRT hardware and software had been recalibrated, these errors were
      reduced to 0.5 +/- 0.1 and 0.18 +/- 0.04 mm respectively, within the manufacturer
      specified 0.5 mm. Results from the 1.0 mm cone were 0.5 +/- 0.3 mm targeting
      accuracy and 0.4 +/- 0.1 mm cone misalignment, within the 0.5 mm specification.
      The results from the 5.0 mm cone were 1.0 +/- 0.2 mm targeting accuracy and 0.18
      +/- 0.06 mm cone misalignment, outside of accuracy specifications. Quality
      assurance of small field IGRT targeting and delivery accuracy is a challenging
      task. The use of a 3D dosimetry technique, where targets are visible on both CBCT
      and optical-CT, enabled identification and quantification of a targeting error in
      3D. After correction, the targeting accuracy of the irradiator was verified to be
      within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified
      to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE(r)/DMOS system
      proved valuable for end-to-end verification of small field IGRT capabilities. 

PMID- 24140984
TI  - Validation of an alternative radiochemical purity method for [99mTc]pentetate
      ([99mTc]DTPA).
AB  - [(99m)Tc]pentetate ([(99m)Tc]DTPA) is the most commonly used radiopharmaceutical
      renography agent. The aim of this work was to validate an alternative method for
      assessing [(99m)Tc]DTPA radiochemical purity (RCP), according to the ICH Q2(R1)
      guidance: "Validation of Analytical Procedures". The proposed method is composed
      of two chromatographic systems. System A is a miniaturized system of thin layer
      chromatography (TLC) silica gel impregnated aluminum strips as stationary phase
      (SP) and distilled water as mobile phase (MP). System B consists of Whatman 1
      paper strips as SP and methyl ethyl ketone as MP. Results indicate that the
      proposed RCP method has been validated, as it is specific, precise, accurate,
      linear and robust. Therefore, it can be used as an alternative method for RCP
      quality control purposes and as stability indicator as well. 

PMID- 24140985
TI  - Generalization ability of fractional polynomial models.
AB  - In this paper, the problem of learning the functional dependency between input
      and output variables from scattered data using fractional polynomial models (FPM)
      is investigated. The estimation error bounds are obtained by calculating the
      pseudo-dimension of FPM, which is shown to be equal to that of sparse polynomial
      models (SPM). A linear decay of the approximation error is obtained for a class
      of target functions which are dense in the space of continuous functions. We
      derive a structural risk analogous to the Schwartz Criterion and demonstrate
      theoretically that the model minimizing this structural risk can achieve a
      favorable balance between estimation and approximation errors. An empirical model
      selection comparison is also performed to justify the usage of this structural
      risk in selecting the optimal complexity index from the data. We show that the
      construction of FPM can be efficiently addressed by the variable projection
      method. Furthermore, our empirical study implies that FPM could attain better
      generalization performance when compared with SPM and cubic splines. 

PMID- 24140986
TI  - Open versus laparoscopic colorectal surgery in the era of multimodality treatment
      of cancer.
AB  - AIM: To compares the efficacy and safety of laparoscopic surgery (LS) and open
      surgery (OS). To analyze early results of a single institution experience using
      adjuvant intraoperative radiation therapy (IORT) presacral boost in locally
      advanced cancer. MATERIAL OF STUDY: 264 patients with curable colorectal cancer
      undergoing laparoscopic (97) or open colorectal resection (167). In 41 patients
      (31 open and 10 laparoscopic resection) with locally advanced rectal cancer we
      performed IORT. Primary endpoints were the evaluation of postoperative clinical
      and oncologic results. RESULTS: Twenty (21%) patients underwent conversion from
      laparoscopic to open surgery. The overall morbidity rates were 17.5% in the LS
      group and 20.9% in the OS group (P= 0.5). Average operative time was shorter in
      the OS than in the LS series (P= 0.01). Use of parenteral narcotics was shorter
      in LS than in OS group (P <0.001), but there were more stoma creations in LS
      group than in OS group (P= 0.001). All patients are alive at different followup
      periods. DISCUSSION: Colorectal cancer is the second leading cause of death from
      malignancy in the industrialized world. The risk of local recurrence after
      treatment increases with tumor stage. The roles of radiochemotherapy and surgical
      procedures have been investigated extensively in the last decades, especially in
      locally advanced rectal cancer. CONCLUSIONS: Laparoscopic techniques can be
      applied to colorectal malignancies without sacrificing oncologic results.
      Multimodality treatment with LS and IORT is safe and feasible.

PMID- 24140987
TI  - Brain-derived neurotrophic factor expression ex vivo in obesity.
AB  - Obesity is associated with an increased risk in neurodegenerative diseases. To
      counteract the neuronal damage, the human body increases brain-derived
      neurotrophic factor (BDNF) expression, leading to neuronal survival and
      plasticity. Recently, peripheral blood mononuclear cells (PBMCs) have been found
      to release BDNF as a potential neuroprotective role of inflammation. Therefore,
      the purpose of this study was to examine whether lipopolysaccharide (LPS)-induced
      PBMC activation would lead to differences in BDNF and inflammatory responses
      between obese and non-obese subjects. Thirty-one subjects (14 obese and 17 non
      obese), ages 18 to 30years, were recruited. PBMCs were cultured for 24h with
      10ng/mL LPS. BDNF, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL
      6) were measured in both plasma and cell culture supernatants. Our results did
      not illustrate any differences in plasma BDNF levels between obese and non-obese
      groups. However, obese subjects elicited a greater plasma IL-6 production, which
      was positively associated with plasma BDNF. Furthermore, LPS-induced PBMCs
      expressed significantly higher BDNF and IL-6 levels in obese subjects compared to
      the non-obese subjects. Finally, these BDNF levels were positively correlated
      with IL-6 response ex vivo. These findings suggest that under a high inflammatory
      state, PBMCs produce greater BDNF and IL-6 expression which may play a
      collaborative role to protect against neuronal damage associated with obesity. 

PMID- 24140988
TI  - Optogenetic examination identifies a context-specific role for
      orexins/hypocretins in anxiety-related behavior.
AB  - Maladaptation to stress is associated with psychopathology. However, our
      understanding of the underlying neural circuitry involved in adaptations to
      stress is limited. Previous work from our lab indicated the paraventricular
      hypothalamic neuropeptides orexins/hypocretins regulate behavioral and
      neuroendocrine responses to stress. To further elucidate the role of orexins in
      adaptation to stress, we employed optogenetic techniques to specifically examine
      the effects of orexin cell activation on behavior in the social interaction test
      and in the home cage as well as orexin receptor 1 internalization and ERK
      phosphorylation in brain regions receiving orexin inputs. In the social
      interaction test, optogenetic stimulation of orexin neurons decreased time spent
      in the interaction zone while increasing the frequency of entries into the
      interaction zone. In addition, optogenetic stimulation of orexin neurons
      increased the total distance traveled in the social interaction arena but had no
      effect on their home cage behavior. Together, these results suggest that orexin
      release increases anxiety in the social interaction test while increasing the
      salience of novel but not familiar environmental stimuli. Consistent with
      activation of orexin neurons, optogenetic stimulation increased orexin receptor1
      internalization and ERK phosphorylation in the paraventricular thalamus (PVT) and
      locus coeruleus (LC), two regions heavily innervated by orexin neurons. Together
      these results show for the first time that elevation of orexin activity, possibly
      in the PVT and LC, is associated with increased anxiety, activity, and arousal in
      a context-specific manner. 

PMID- 24140989
TI  - Spatial delayed nonmatching-to-sample performances in long-living Ames dwarf
      mice.
AB  - Ames dwarf mice have an extended lifespan by comparison with normal mice.
      Behavioral testing has revealed that sometimes Ames dwarf mice also evince
      superior performances relative to normal mice, but in other cases they do not. In
      this experiment, Ames dwarf and normal mice were compared on a T-maze test and on
      a delayed nonmatching-to-sample variant of a T-maze test. On the simple T-maze,
      Ames dwarf and normal mice committed comparable numbers of errors. On the
      nonmatching-to-sample task, normal mice mastered the discrimination by the end of
      the experiment while Ames dwarf mice did not. The apparatus, distances traveled
      and session duration were equivalent between the two tasks. The poorer
      performances of Ames dwarf mice on the nonmatching-to-sample task suggests that
      Ames dwarf mice may not be as capable of learning relatively cognitively complex
      tasks as normal mice. 

PMID- 24140990
TI  - Conductance of partially disordered graphene: crossover from temperature
      dependent to field-dependent variable-range hopping.
AB  - We report an analysis of low-temperature measurements of the conductance of
      partially disordered reduced graphene oxide, finding that the data follow a
      simple crossover scenario. At room temperature, the conductance is dominated by
      two-dimensional (2D) electric field-assisted, thermally driven (Pollak-Riess)
      variable-range hopping (VRH) through highly disordered regions. However, at lower
      temperatures T, we find a smooth crossover to follow the exp(-E0/E)(1/3) field
      driven (Shklovskii) 2D VRH conductance behaviour when the electric field E
      exceeds a specific crossover value EC(T)(2D) = (EaE(1/3)0 /3)(3/4) determined by
      the scale factors E0 and Ea for the high-field and intermediate-field regimes
      respectively. Our crossover scenario also accounts well for experimental data
      reported by other authors for three-dimensional disordered carbon networks,
      suggesting wide applicability.

PMID- 24140992
TI  - Orthographic learning and self-teaching in a bilingual and biliterate context.
AB  - The aim of this study was to examine self-teaching in the context of English as a
      foreign language literacy acquisition. Three groups comprising 88 sixth-grade
      children participated. The first group consisted of Russian-Hebrew-speaking
      bilinguals who had acquired basic reading skills in Russian as their first
      language (L1) and literacy and who were literate in Hebrew as a second language.
      The second group consisted of Russian-Hebrew-speaking bilinguals who had not
      learned to read in their native Russian but had acquired Hebrew as their first
      literate language. The third group consisted of Hebrew-speaking monolingual
      children who were literate in Hebrew. This design facilitated examining the
      effect of biliteracy and bilingualism on basic English reading skills. We
      hypothesized that due to the proximity between the Russian and English
      orthographies as opposed to the Hebrew-English "distance," the Russian-Hebrew
      speaking biliterate group who acquired basic reading and spelling skills in L1
      Russian would have superior self-teaching in English as opposed to the two other
      groups. The standard two-session self-teaching paradigm was employed with naming
      (speed and accuracy) and orthographic choice as posttest measures of orthographic
      learning. Results showed that after 4 years of English instruction, all three
      groups showed evidence of self-teaching on naming speed and orthographic
      recognition. The Russian-Hebrew-speaking biliterate group, moreover, showed a
      partial advantage over the comparison groups for initial decoding of target
      pseudowords and clear-cut superiority for measures of later orthographic
      learning, thereby showing self-teaching while supporting the script dependence
      hypothesis.

PMID- 24140991
TI  - Belief-based action prediction in preverbal infants.
AB  - Successful mindreading entails both the ability to think about what others know
      or believe, and to use this knowledge to generate predictions about how mental
      states will influence behavior. While previous studies have demonstrated that
      young infants are sensitive to others' mental states, there continues to be much
      debate concerning how to characterize early theory of mind abilities. In the
      current study, we asked whether 6-month-old infants appreciate the causal role
      that beliefs play in action. Specifically, we tested whether infants generate
      action predictions that are appropriate given an agent's current belief. We
      exploited a novel, neural indication of action prediction: motor cortex
      activation as measured by sensorimotor alpha suppression, to ask whether infants
      would generate differential predictions depending on an agent's belief. After
      first verifying our paradigm and measure with a group of adult participants, we
      found that when an agent had a false belief that a ball was in the box, motor
      activity indicated that infants predicted she would reach for the box, but when
      the agent had a false belief that a ball was not in the box, infants did not
      predict that she would act. In both cases, infants based their predictions on
      what the agent, rather than the infant, believed to be the case, suggesting that
      by 6months of age, infants can exploit their sensitivity to other minds for
      action prediction. 

PMID- 24140993
TI  - Implementation of the ALERT algorithm, a new dispatcher-assisted telephone
      cardiopulmonary resuscitation protocol, in non-Advanced Medical Priority Dispatch
      System (AMPDS) Emergency Medical Services centres.
AB  - OBJECTIVES: Early bystander cardiopulmonary resuscitation (CPR) is a key factor
      in improving survival from out-of-hospital cardiac arrest (OHCA). The ALERT
      (Algorithme Liegeois d'Encadrement a la Reanimation par Telephone) algorithm has
      the potential to help bystanders initiate CPR. This study evaluates the
      effectiveness of the implementation of this protocol in a non-Advanced Medical
      Priority Dispatch System area. METHODS: We designed a before and after study
      based on a 3-month retrospective assessment of victims of OHCA in 2009, before
      the implementation of the ALERT protocol in Liege emergency medical communication
      centre (EMCC), and the prospective evaluation of the same 3 months in 2011,
      immediately after the implementation. RESULTS: At the moment of the call,
      dispatchers were able to identify 233 OHCA in the first period and 235 in the
      second. Victims were predominantly male (59%, both periods), with mean ages of
      64.1 and 63.9 years, respectively. In 2009, only 9.9% victims benefited from
      bystander CPR, this increased to 22.5% in 2011 (p<0.0002). The main reasons for
      protocol under-utilisation were: assistance not offered by the dispatcher
      (42.3%), caller physically remote from the victim (20.6%). Median time from call
      to first compression, defined here as no flow time, was 253s in 2009 and 168s in
      2011 (NS). Ten victims were admitted to hospital after ROSC in 2009 and 13 in
      2011 (p=0.09). CONCLUSION: From the beginning and despite its under-utilisation,
      the ALERT protocol significantly improved the number of patients in whom
      bystander CPR was attempted.

PMID- 24140994
TI  - Emergency medical dispatch. With increasing research it is important to unify the
      reporting.

PMID- 24140995
TI  - Differences between the human eye and the spectrophotometer in the shade matching
      of tooth colour.
AB  - OBJECTIVES: The aim of this work was to assess the agreement between instrumental
      and visual colour matching. METHODS: Shade selection with the 3DMaster Toothguide
      (Vita-Zahnfabrik) was performed for 1361 maxillary central incisors and compared
      with the shade obtained with the EasyShade Compact (Vita-Zahnfabrik)
      spectrophotometer. RESULTS: We observed a greater correlation between the
      objective method and the subjective one in the colour dimension of lightness
      (Kappa 0.6587), followed by hue (Kappa 0.4337) and finally chroma (Kappa 0.3578).
      CONCLUSION: The colour dimension in which the greatest agreement is seen between
      the operator and the spectrophotometer is value or lightness. CLINICAL
      SIGNIFICANCE: This study reveals differences between the measurement of colour
      via spectrophotometry and the visual shade selection method. According to our
      results, there is better agreement in the value or lightness colour dimension,
      which is the most important one in the choice of tooth colour.

PMID- 24140996
TI  - Laser-interstitial thermal therapy for refractory cerebral edema from post
      radiosurgery metastasis.
AB  - BACKGROUND: Stereotactic radiosurgery is often an effective tool for the
      treatment of brain metastases. A complication of radiosurgical treatment for
      brain metastasis can be persistent cerebral edema. Treatments of this refractory
      cerebral edema include observation, corticosteroids, and surgical resection of
      the edema-inducing mass. Laser-interstitial thermal therapy is a minimally
      invasive technique for ablating intracranial lesions. It may provide a treatment
      option for metastases after radiosurgery causing refractory cerebral edema. CASE
      DESCRIPTION: We report the case of a 64-year-old man with lung adenocarcinoma
      presenting to our department with left hemiparesis. Brain magnetic resonance
      imaging showed an 18-mm enhancing lesion in the right external capsule with
      significant surrounding edema. The lesion was treated by radiosurgery. There was
      persistent edema after radiosurgery. The patient required continued
      corticosteroid therapy to maintain his ability to ambulate. He developed
      refractory hyperglycemia, weight gain, and bilateral proximal muscle weakness
      secondary to this therapy. Fourteen weeks after radiosurgery, he underwent laser
      interstitial thermal therapy for lesion ablation. He was weaned off
      corticosteroids during 2 weeks and maintained his strength during the following
      month. CONCLUSIONS: Laser-interstitial thermal therapy may be a treatment option
      for refractory cerebral edema after stereotactic radiosurgery to a metastasis.
      This therapy may be of particular use in deep-seated lesions refractory to
      corticosteroid therapy.

PMID- 24140997
TI  - Evaluation of a 3-dimensional voxel-based neuronavigation system with perspective
      image rendering for keyhole approaches to the skull base: an anatomical study.
AB  - BACKGROUND: Keeping track of the endoscope tip in 3 planes (axial, coronal, and
      sagittal) while performing skull base surgeries can be difficult because the
      surgeon is focused most on the live video images of the endoscope. For that
      reason, it was the aim of this anatomical cadaver study to evaluate the
      usefulness of a voxel-based neuronavigation system with 3-dimensional (3D)
      perspective image rendering for endoscopic procedures through keyhole approaches
      to the skull base. METHODS: On 5 whole-body fixed cadavers, frontolateral and
      retrosigmoid approaches were performed bilaterally using a neuronavigation system
      with 3D perspective image rendering (Cbyon, Med-Surgical Services Inc.,
      Sunnyvale, California). Target points defined on the selected target structures
      were approached with the navigated ? 4-mm 0 degrees  endoscope (Storz,
      Tuttlingen, Germany). Using an Endocameleon 4-mm rigid endoscope capable of
      changing its angle of view while remaining stationary, the surgical field was
      checked for injuries before and after insertion of the navigated 0 degrees 
      endoscope. RESULTS: The median neuronavigation registration error was 0.95 mm
      (range 0.6 to 1.2 mm). Evaluation showed that 100% of the defined targets were
      reached and visualized. Neither a target structure nor neurovascular structures
      or surrounding brain tissue were injured by the navigated 0 degrees  endoscope.
      CONCLUSIONS: A neuronavigation system with 3D voxel-based perspective image
      rendering could potentially improve safety during complex skull base surgeries,
      and possibly also help to improve surgical results. Such a system, however,
      cannot replace a neurosurgeon's experience nor surgical skill or anatomical
      knowledge. It is an excellent teaching tool for young neurosurgeons, but it also
      has some limitations. Therefore, clinical studies will be necessary to further
      evaluate the benefits of this type of neuronavigation system in a clinical
      setting.

PMID- 24140998
TI  - Pituitary dysfunction after aneurysmal subarachnoid hemorrhage is associated with
      impaired early outcome.
AB  - OBJECTIVE: Poor outcome and neuropsychological sequelae after aneurysmal
      subarachnoid hemorrhage (SAH) is a persistent problem. Pituitary dysfunction has
      been proposed as a contributing factor. Clinical studies have given variable and
      conflicting results on its importance and incidence after SAH. The aim of this
      study was to prospectively examine SAH patients with assessment of endocrine
      function in the acute stage and at early follow-up and to compare clinical SAH
      features to endocrine abnormalities indicating pituitary dysfunction. METHODS:
      Endocrine function was assessed by basal hormonal concentrations at 5 to 10 days
      and 3 to 6 months after SAH. Growth hormone deficiency also was evaluated by the
      growth hormone releasing hormone-arginine stimulation test at follow-up. Clinical
      outcome was assessed and scored according to the Glasgow Outcome Scale. RESULTS:
      Fifty-one SAH patients were included and assessed in the acute stage after the
      bleed. Six were lost to follow-up. The overall prevalence of pituitary
      dysfunction was 37% and 27% in the acute stage and at follow-up, respectively.
      Patients with evidence of pituitary dysfunction had significantly worse outcome
      according to Glasgow Outcome Scale at both occasions. The ruptured aneurysm was
      more commonly located in the circle of Willis among patients with pituitary
      dysfunction in the acute stage. CONCLUSIONS: The present results support earlier
      findings that hormonal abnormalities are not infrequent after SAH. Furthermore,
      our data suggest that pituitary dysfunction is associated with worse clinical
      outcome and is more common among patients with bleeding sites close to the
      hypothalamus.

PMID- 24140999
TI  - Endoscopic vascular decompression for the treatment of trigeminal neuralgia:
      clinical outcomes and technical note.
AB  - OBJECTIVE: This study sought to describe the operative technique and clinical
      outcomes in a series of 57 patients with trigeminal neuralgia treated with
      endoscopic vascular decompression (EVD) alone without the use of microscopy at
      any point. METHODS: A prospective observational study was performed on 57
      consecutive patients treated with EVD alone for trigeminal neuralgia from October
      2005 to October 2010. Patient outcomes were evaluated with respect to pain
      abatement, complication rate, length of hospital stay, and overall operative
      time. Pain outcome was graded using the Barrow Neurological Institute pain
      intensity score (BNI), with BNI 1 considered an excellent result and BNI 2 or 3
      considered a good result. Follow-up ranged from 12 to 72 months, with a mean of
      32 months. In addition to reporting these cases, our operative technique for EVD
      is described in detail. RESULTS: All 57 patients reported severe preoperative
      pain (BNI 5); 100% of patients achieved immediate postoperative pain control or
      complete pain relief (BNI 1 to 3), with 82% obtaining an excellent result of BNI
      1, and 18% of patients reported good results of BNI 2 or 3. At follow-up, 56 of
      57 patients (98%) reported complete relief or well controlled pain (BNI 1 to 3),
      with 75% obtaining an excellent result of BNI 1; 23% of patients obtained a good
      result of BNI 2 or 3. The complication rate was 4%, with no mortality. Mean
      length of hospital stay was 1.6 days, with a range of 1 to 5 days; mean operative
      time was 133 minutes. CONCLUSIONS: EVD is a safe and highly effective alternative
      to the more traditional open microvascular decompression or the more recently
      developed endoscopically assisted microvascular decompression.

PMID- 24141000
TI  - Development of three-dimensional hollow elastic model for cerebral aneurysm
      clipping simulation enabling rapid and low cost prototyping.
AB  - OBJECTIVE: We developed a method for fabricating a three-dimensional hollow and
      elastic aneurysm model useful for surgical simulation and surgical training. In
      this article, we explain the hollow elastic model prototyping method and report
      on the effects of applying it to presurgical simulation and surgical training.
      METHODS: A three-dimensional printer using acrylonitrile-butadiene-styrene as a
      modeling material was used to produce a vessel model. The prototype was then
      coated with liquid silicone. After the silicone had hardened, the acrylonitrile
      butadiene-styrene was melted with xylene and removed, leaving an outer layer as a
      hollow elastic model. RESULTS: Simulations using the hollow elastic model were
      performed in 12 patients. In all patients, the clipping proceeded as scheduled.
      The surgeon's postoperative assessment was favorable in all cases. This method
      enables easy fabrication at low cost. CONCLUSION: Simulation using the hollow
      elastic model is thought to be useful for understanding of three-dimensional
      aneurysm structure.

PMID- 24141001
TI  - Clinical outcomes of intracerebral hemorrhage in hemodialysis patients.
AB  - BACKGROUND: Chronic renal failure (CRF) is associated with a high incidence of
      stroke. In particular, the mortality rate for intracerebral hemorrhage (ICH)
      patients with hemodialysis (HD) due to advanced stage CRF is high, and the annual
      number of such cases is increasing. Therefore, we retrospectively investigated 5
      years of clinical data from patients with ICH in our institution to reveal
      differences in the clinical courses of HD and non-HD patients and to identify
      risk factors for poor outcomes in ICH patients with HD. METHODS: Three hundred
      sixty-six consecutive patients with nontraumatic spontaneous ICH, 91% of whom did
      not receive HD (non-HD group) and 9% of whom received HD for the treatment of CRF
      (HD group), were enrolled. Clinical data, including the presence of
      intraventricular hemorrhage (IVH), microbleeds, modified Rankin scale scores,
      previous medical disease history, the presence of HD, and the days on which ICH
      occurred, were evaluated. RESULTS: In a comparison of HD patients and non-HD
      patients, the HD patients had higher rates of hematomas in the basal ganglia,
      IVH, use of antihypertensive drugs, antidiabetic drugs, and
      antiplatelet/anticoagulants. The mortality rate was higher in the HD group (44%)
      than in the non-HD group (21%). In the HD group, the risk factors associated with
      mortality were hematoma volume, the presence of IVH, and lack of antihypertensive
      drug use. Eighty-five percent of the ICH occurred on intermittent HD days or
      before the HD procedure on an HD day. CONCLUSIONS: Mortality in ICH patients with
      HD was associated with lack of antihypertensive drug use. Therefore, strict
      control of blood pressure is needed in HD patients to prevent ICH, especially on
      intermittent HD days or before the HD procedure.

PMID- 24141002
TI  - Diagnostic and surgical implications of ventral vertebrobasilar displacement by
      posterior fossa neurenteric cysts.
AB  - OBJECTIVE: Neurenteric cysts (NECs) are uncommonly encountered lesions of the
      central nervous system with heterogeneous imaging characteristics. The object of
      this study was to review the preoperative imaging findings represented among a
      cohort of surgically treated posterior fossa NECs. These findings are considered
      in the context of surgical technique, and inform an understanding of aberrant
      neuroembryological development associated with NECs. METHODS: A single
      institution, multisurgeon series of 7 consecutive patients (5 female and 2 male
      patients, mean age 36 years, range 19 to 57 years) treated surgically for
      histopathologically confirmed posterior fossa NECs was retrospectively reviewed.
      Lesion imaging and anatomic characteristics were noted on preoperative magnetic
      resonance imaging (MRI). Imaging comparisons were made against an additional
      cohort of 266 consecutive surgically treated posterior fossa masses to validate
      unique anatomic findings. RESULTS: T1 and T2 MRI signal characteristics were
      variable when compared across lesions. All NECs were found to be anteriorly
      located within the posterior fossa, but always situated between the brainstem
      pial surface and the vertebrobasilar system, causing ventral displacement of
      vertebrobasilar vessels. CONCLUSIONS: Posterior fossa NECs display variable
      patterns of MRI signal and are commonly considered as part of a broad
      differential of cystic posterior fossa masses. We identified tumor insinuation
      between the ventral brainstem and vertebrobasilar system as a highly sensitive
      and specific radiographic sign for NECs. This finding was not observed among a
      large cohort of posterior fossa masses representative of other multiple
      pathologies.

PMID- 24141003
TI  - Astroblastomas: a Surveillance, Epidemiology, and End Results (SEER)-based
      patterns of care analysis.
AB  - OBJECTIVE: This study sought to report patient characteristics, risk factors, and
      trends in management for astroblastoma patients. METHODS: A retrospective
      analysis was conducted utilizing the Surveillance, Epidemiology and End Results
      Program of the National Cancer Institute. RESULTS: Two hundred and thirty-nine
      patients were identified, with 206 patients receiving treatment. The median age
      at diagnosis was 35 years (range 0 to 84 years). Tumor location was available for
      177 patients, and the majority were supratentorial (n = 144, 81.3%). The median
      overall survival and cause-specific survival for the cohort receiving treatment
      was 55 and 65 months, respectively. On univariate analysis, patients receiving
      surgery alone compared to only radiotherapy displayed improved overall survival
      (OS) and cause-specific survival (CSS) with a 5-year OS of 62.2% vs. 27.3%, P <
      .001, and CSS of 67.3% vs. 31.9%, P = .003. Supratentorial tumor location was
      associated with worse survival, with an estimated 5-year OS of 44.9% for
      supratentorial tumors compared to 75% for infratentorial tumors (hazard ratio
      3.41 [95% CI, 1.76 to 6.62]; P < .001) and CSS of 47.5% (supratentorial) to 82%
      (infratentorial) (hazard ratio 3.95 [95% CI, 1.81 to 8.62]; P = .001). Age >60
      years at diagnosis and treatment before 1990 were correlated with decreased
      survival on both the univariate and the multivariate analyses. CONCLUSIONS: To
      our knowledge, this is the largest report of astroblastoma patients described in
      the literature. Supratentorial tumor location, older age, and treatment prior to
      1990 were poor prognostic factors.

PMID- 24141004
TI  - Outcomes of screening endometrial cancer patients for Lynch syndrome by patient
      administered checklist.
AB  - OBJECTIVE: The aims of this study were to implement a patient-administered
      checklist designed to identify endometrial cancer patients at elevated risk for
      Lynch syndrome; measure subsequent genetic counseling and testing; and identify
      differences between those who attended genetic counseling and those who did not.
      METHODS: We developed a 4-item yes/no checklist of personal and family history
      risk factors for Lynch syndrome-associated endometrial cancer and recommended
      referral for genetic counseling for patients meeting any of the criteria.
      Retrospective chart review was performed to determine subsequent genetic
      counseling and testing outcomes over a 15 month period. RESULTS: 6/387 (1.6%) of
      endometrial cancer patients tested positive for a Lynch syndrome mutation. 4/24
      (17%) of endometrial cancer patients who met referral criteria and attended
      genetic counseling tested positive. 38/70 (55%) of patients who met referral
      criteria were not seen for genetic counseling. Patients who were diagnosed with
      endometrial cancer at younger ages, who had primary surgery at our institution,
      or who met more than one referral criteria were more likely to be seen for
      genetic counseling. CONCLUSIONS: Endometrial cancer patients who met referral
      criteria and attended genetic counseling comprised a population enriched for
      Lynch syndrome. This approach allowed Lynch syndrome evaluation resources to be
      targeted to a population of patients that is high risk and interested in the
      information. The referral rate of at-risk patients needs to be improved, and
      allocating resources towards this goal could increase the identification of Lynch
      syndrome while avoiding some of the pitfalls of universal screening.

PMID- 24141005
TI  - Neutron powder diffraction and molecular dynamics study of superionic SrBr2.
AB  - The nature of the dynamic ionic disorder within the high-temperature superionic
      phase of strontium bromide, beta-SrBr2, has been investigated using reverse Monte
      Carlo (RMC) modelling of neutron powder diffraction data and complementary ab
      initio molecular dynamics (MD) simulations. The RMC and MD results are in good
      agreement and indicate the presence of extensive dynamic disorder within the Br(
      ) sublattice of the cubic fluorite structure. Rapid anion diffusion predominantly
      occurs as hops between nearest neighbour sites in the <100> directions, though
      the trajectories are markedly curved and pass through the peripheries of the
      octahedral voids in the cation sublattice. In addition, there are extensive
      correlations between the motions of individual Br(-), often leading to the
      formation of a short-lived square antiprism co-ordination environment around the
      Sr(2+). Such polyhedra are observed within the (ambient temperature) ordered
      tetragonal crystal structure of alpha-SrBr2. The nature of the ionic disorder in
      SrBr2 is of particular interest because it is the only known example of a Br(-)
      ion superionic. Owing to the large size of this anion, a comparison with the
      behaviour of other superionic phases gives an insight into the role of ionic size
      on the conducting properties within these materials. 

PMID- 24141006
TI  - Combination of the Hematopoietic Cell Transplantation Comorbidity Index and the
      European Group for Blood and Marrow Transplantation score allows a better
      stratification of high-risk patients undergoing reduced-toxicity allogeneic
      hematopoietic cell transplantation.
AB  - This study was conducted to determine whether the integration of the
      Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European
      Group for Blood and Marrow Transplantation (EBMT) score would improve individual
      capacity for stratification of high-risk HCT candidates. A total of 442
      consecutive patients receiving an allogeneic HCT after reduced-toxicity
      conditioning was included. Final HCT-CI and EBMT scores were calculated and
      validated. Then, patients were grouped into a 6-category new combination model
      according to the HCT-CI (0, 1 to 2, >= 3) and EBMT scores (0 to 3, 4 to 7), and
      the model's predictive capacity was also evaluated. Median HCT-CI and EBMT scores
      were 3 and 4, respectively. Increased HCT-CI was associated with higher 4-year
      nonrelapse mortality (NRM) and lower 4-year overall survival (OS), whereas a high
      EBMT score was associated with higher 4-year NRM. The HCT-CI showed a trend for a
      better predictive capacity than the EBMT score (c-statistic .6 versus .54, P =
      .1). According to the new model, patients within HCT-CI of 0 and HCT-CI of 1 to 2
      groups had similar risk of NRM independently of their EBMT score. Within the HCT
      CI >= 3 group, patients with low EBMT score showed lower NRM (25% versus 40%, P =
      .04) and a trend to higher OS (52% versus 36%, P = .06) than patients with a high
      EBMT score. Moreover, patients with HCT-CI >= 3 and EBMT score 0 to 3 had similar
      outcomes than those with HCT-CI of 1 to 2. In conclusion, the combination of HCT
      CI and the EBMT score is feasible and might contribute to a better identification
      of high-risk patients, improving selection of best allogeneic HCT candidates.

PMID- 24141007
TI  - Optimizing autologous stem cell mobilization strategies to improve patient
      outcomes: consensus guidelines and recommendations.
AB  - Autologous hematopoietic stem cell transplantation (aHSCT) is a well-established
      treatment for malignancies such as multiple myeloma (MM) and lymphomas. Various
      changes in the field over the past decade, including the frequent use of tandem
      aHSCT in MM, the advent of novel therapies for the treatment of MM and lymphoma,
      and the addition of new stem cell mobilization techniques, have led to the need
      to reassess current stem cell mobilization strategies. Mobilization failures with
      traditional strategies are common and result in delays in treatment and increased
      cost and resource utilization. Recently, plerixafor-containing strategies have
      been shown to significantly reduce mobilization failure rates, but the ideal
      method to maximize stem cell yields and minimize costs associated with collection
      has not yet been determined. A panel of experts convened to discuss the currently
      available data on autologous hematopoietic stem cell mobilization and
      transplantation and to devise guidelines to optimize mobilization strategies.
      Herein is a summary of their discussion and consensus. 

PMID- 24141008
TI  - Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell
      transplantation: long-term follow-up of a randomized study.
AB  - We report the long-term results of a prospective randomized study on the use of
      ursodeoxycholic acid (UDCA) for prevention of hepatic complications after
      allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with
      malignant disease, were randomized to receive (n = 123) or not to receive (n =
      119) UDCA from the beginning of the conditioning until 90 days post
      transplantation. The results were reported after 1-year follow-up. UDCA
      administration reduced significantly the proportion of patients developing high
      serum bilirubin levels as well as the incidence of severe acute graft-versus-host
      disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group,
      nonrelapse mortality (NRM) was lower and overall survival better than in the
      control group. After a 10-year follow-up, the difference in the survival and NRM
      in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48%
      versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in
      patients surviving at 1 year post-transplantation showed no significant
      differences between the study groups in the long-term follow-up in chronic GVHD,
      relapse rate, NRM, disease-free survival, or overall survival. These long-term
      results continue to support the useful role of UDCA in the prevention of
      transplant-related complications in allogeneic transplantation.

PMID- 24141009
TI  - High-dose etoposide plus granulocyte colony-stimulating factor as an effective
      chemomobilization regimen for autologous stem cell transplantation in patients
      with non-Hodgkin Lymphoma previously treated with CHOP-based chemotherapy: a
      study from the Consortium for Improving Survival of Lymphoma.
AB  - We conducted a multicenter retrospective study to compare the efficacy and
      toxicity of various chemomobilization regimens: high-dose (HD) cyclophosphamide,
      HD etoposide (VP-16), and platinum-based chemotherapies. We reviewed the
      experiences of 10 institutions with 103 non-Hodgkin lymphoma patients who had
      previously only been treated with cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP)-based chemotherapy. The mobilization yields for each regimen
      were analyzed. HD VP-16 mobilized a significantly higher median number of CD34(+)
      cells (16.22 * 10(6) cells/kg) than HD cyclophosphamide (4.44 * 10(6) cells/kg)
      or platinum-based chemotherapies (6.08 * 10(6) cells/kg, P < .001). The rate of
      successful mobilization (CD34(+) cell count >= 5.0 * 10(6) cells/kg) was also
      significantly higher for HD VP-16 (86%) than for HD cyclophosphamide (45%) or
      platinum-based chemotherapies (61%, P = .004). The successful mobilization rate
      on day 1 of 72% for HD VP-16 was significantly higher than the rates for HD
      cyclophosphamide (13%) and platinum-based chemotherapies (26%, P < .001). In
      multivariate analysis, HD VP-16 was a significant predictor of successful
      mobilization (P = .014; odds ratio, 5.25; 95% confidence interval, 1.40 to
      19.63). Neutropenic fever occurred in 67% of patients treated with HD VP-16. The
      incidence was similar for HD cyclophosphamide (58%, P = .454) but was
      significantly lower for platinum-based chemotherapies (12%, P < .001). However,
      fatal (grade >= 4) infection and treatment-related mortality were not observed in
      this study. In conclusion, the mobilization yield was significantly influenced by
      the chemomobilization regimen, and HD VP-16 was a highly effective mobilization
      regimen in patients with non-Hodgkin lymphoma.

PMID- 24141010
TI  - Minor antigen distribution predicts site-specific graft-versus-tumor activity of
      adoptively transferred, minor antigen-specific CD8 T Cells.
AB  - The clinical success of allogeneic T cell therapy for cancer relies on the
      selection of antigens that can effectively elicit antitumor responses with
      minimal toxicity toward nonmalignant tissues. Although minor histocompatibility
      antigens (MiHA) represent promising targets, broad expression of these antigens
      has been associated with poor responses and T cell dysfunction that may not be
      prevented by targeting MiHA with limited expression. In this study, we
      hypothesized that antitumor activity of MiHA-specific CD8 T cells after
      allogeneic bone marrow transplantation (BMT) is determined by the distribution of
      antigen relative to the site of tumor growth. To test this hypothesis, we
      utilized the clinically relevant male-specific antigen HY and studied the fate of
      adoptively transferred, HY-CD8(+) T cells (HY-CD8) against a HY-expressing
      epithelial tumor (MB49) and pre-B cell leukemia (HY-E2APBX ALL) in BMT
      recipients. Transplants were designed to produce broad HY expression in
      nonhematopoietic tissues (female -> male BMT, [F -> M]), restricted HY expression
      in hematopoietic tissues (male -> female BMT, [M -> F]) tissues, and no HY tissue
      expression (female -> female BMT, [F -> F]). Broad HY expression induced poor
      responses to MB49 despite sublethal graft-versus-host disease and accumulation of
      HY-CD8 in secondary lymphoid tissues. Antileukemia responses, however, were
      preserved. In contrast, restriction of HY expression to hematopoietic tissues
      restored MB49 responses but resulted in a loss of antileukemia responses. We
      concluded that target alloantigen expression in the same compartment of tumor
      growth impairs CD8 responses to both solid and hematologic tumors.

PMID- 24141011
TI  - Benchmarks for acute stroke care delivery.
AB  - OBJECTIVE: Despite widespread interest in many jurisdictions in monitoring and
      improving the quality of stroke care delivery, benchmarks for most stroke
      performance indicators have not been established. The objective of this study was
      to develop data-derived benchmarks for acute stroke quality indicators. DESIGN:
      Nine key acute stroke quality indicators were selected from the Canadian Stroke
      Best Practice Performance Measures Manual. PARTICIPANTS: A population-based
      retrospective sample of patients discharged from 142 hospitals in Ontario,
      Canada, between 1 April 2008 and 31 March 2009 (N = 3191) was used to calculate
      hospital rates of performance and benchmarks. INTERVENTION: The Achievable
      Benchmark of Care (ABCTM) methodology was used to create benchmarks based on the
      performance of the upper 15% of patients in the top-performing hospitals. MAIN
      OUTCOME MEASURES: Benchmarks were calculated for rates of neuroimaging, carotid
      imaging, stroke unit admission, dysphasia screening and administration of stroke
      related medications. RESULTS: The following benchmarks were derived: neuroimaging
      within 24 h, 98%; admission to a stroke unit, 77%; thrombolysis among patients
      arriving within 2.5 h, 59%; carotid imaging, 93%; dysphagia screening, 88%;
      antithrombotic therapy, 98%; anticoagulation for atrial fibrillation, 94%;
      antihypertensive therapy, 92% and lipid-lowering therapy, 77%. ABCTM acute stroke
      care benchmarks achieve or exceed the consensus-based targets required by
      Accreditation Canada, with the exception of dysphagia screening. CONCLUSIONS:
      Benchmarks for nine hospital-based acute stroke care quality indicators have been
      established. These can be used in the development of standards for quality
      improvement initiatives.

PMID- 24141012
TI  - The Global Trigger Tool shows that one out of seven patients suffers harm in
      Palestinian hospitals: challenges for launching a strategic safety plan.
AB  - OBJECTIVE: The aim of this study was to evaluate patient safety levels in
      Palestinian hospitals and to provide guidance for policymakers involved in safety
      improvement efforts. DESIGN: Retrospective review of hospitalized patient records
      using the Global Trigger Tool. SETTING: Two large hospitals in Palestine: a
      referral teaching hospital and a nonprofit, non-governmental hospital.
      PARTICIPANTS: A total of 640 random records of discharged patients were reviewed
      by experienced nurses and physicians from the selected hospitals. INTERVENTION:
      Assessment of adverse events. MAIN OUTCOME MEASURES: Prevalence of adverse
      events, their preventability and harm category. Descriptive statistics and Cohen
      kappa coefficients were calculated. RESULTS: One out of seven patients (91
      [14.2%]) suffered harm. Fifty-four (59.3%) of these events were preventable; 64
      (70.4%) resulted in temporary harm, requiring prolonged hospitalization. Good
      reliability was achieved among the independent reviewers in identifying adverse
      events. The Global Trigger Tool showed that adverse events in Palestinian
      hospitals likely occur at a rate of 20 times higher than previously reported.
      Although reviewers reported that detecting adverse events was feasible, we
      identified conditions suggesting that the tool may be challenging to use in daily
      practice. CONCLUSION: One out of seven patients suffers harm in Palestinian
      hospitals. Compromised safety represents serious problems for patients, hospitals
      and governments and should be a high priority public health issue. We argue that
      direct interventions should be launched immediately to improve safety. Additional
      costs associated with combating adverse events should be taken into
      consideration, especially in regions with limited resources, as in Palestine.

PMID- 24141013
TI  - Bridging the ivory towers and the swampy lowlands; increasing the impact of
      health services research on quality improvement.
AB  - Decisions about how to organize and deliver health services are often more
      complex and seemingly less rational than decisions about what clinical care to
      provide. The concept of 'Evidence-Based Management', or what might more
      appropriately be termed 'Evidence-Informed Improvement', does not seem to have
      captured the hearts and minds of the people responsible for managing health-care
      provision. Organizational decision-making is more likely to be influenced by
      political, ideological and pragmatic factors, and by the personal experience of
      the decision-makers, than by science. Whilst some people would regard the
      messiness of management decision-making as inevitable, most would accept that
      decisions could be improved by making greater use of the established health
      service research evidence, and through a stronger commitment to developing new
      evidence. Over the last two or more decades the evidence base created by Health
      Service Researchers has grown in quantity and in quality and yet much of it
      remains invisible to the people who most need to use it. This paper explores how
      the disconnect between the traditional 'producers' of research evidence in
      academia, and the managerial and clinical 'consumers' of that evidence, has
      contributed to the challenge of embedding an evidence-informed approach to
      service improvement. The advantages of a closer working relationship between
      academia and health services are outlined and three approaches to evidence
      creation and utilization are described which attempt to maximize the influence of
      scientific evidence on managerial practice. 

PMID- 24141014
TI  - Incidence of adverse drug events in an academic hospital: a prospective cohort
      study.
AB  - OBJECTIVE: To determine the incidence of adverse drug events (ADEs) and assess
      their severity and preventability. DESIGN: A prospective cohort study. SETTING: A
      900-bed tertiary academic hospital. PARTICIPANTS: A total of 977 patients
      admitted to two medical, one surgical and two intensive care units over four
      months. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of ADEs,
      preventability of ADEs, potential ADEs and medication errors. A physician and a
      clinical pharmacist independently determined the likelihood that incidents were
      caused by medications and judged severity and preventability. RESULTS:
      Pharmacists reviewed the medical records of the 977 patients. Pharmacists
      identified 361 incidents, of which 281 (78%) were considered to be an ADE,
      potential ADE or medication error by reviewers. The incidence of ADEs was 8.5 per
      100 admissions (95% confidence interval (CI) 6.8-10.4), with the highest rate
      found in the intensive care unit (21.1 per 100 admissions) (95% CI 15.1-28.8). Of
      all ADEs, 59% were rated as significant, 35% as serious and 6% as life
      threatening. Thirty percent of ADEs were preventable and 96% of these occurred in
      the ordering stage. The incidence of potential ADEs was 13.8 per 100 admissions
      (95% CI 11.5-16.2). Overall, 223 medication errors were identified, 66 (30%) were
      harmless, 132 (59%) had the potential to cause harm and 25 (11%) resulted in
      harm. CONCLUSIONS: The incidence of ADEs in a Saudi Hospital was 8.5 per 100
      admissions. Preventable ADEs most commonly occurred in the ordering stage;
      therefore, interventions to reduce ADEs should target the ordering stage.

PMID- 24141015
TI  - Dual roles for splice variants of the glucuronidation pathway as regulators of
      cellular metabolism.
AB  - Transcripts of the UGT1A gene, encoding half of human UDP-glucuronosyltransferase
      (UGT) enzymes, undergo alternative splicing, resulting in active enzymes named
      isoforms 1 (i1s) and novel truncated isoforms 2 (i2s). Here, we investigated the
      effects of depleting endogenous i2 on drug response and attempted to unveil any
      additional biologic role(s) for the truncated novel UGT proteins. We used an
      integrated systems biology approach that combines RNA interference with unbiased
      global genomic and proteomic screens, and used HT115 colorectal cancer cells as a
      model. Consistent with previous evidence suggesting that i2s negatively regulate
      i1s through protein-protein interactions, i2-depleted cells were less sensitive
      to drug-induced cell death (IC50 of 0.45 +/- 0.05 uM versus 0.22 +/- 0.03 uM; P =
      0.006), demonstrating that modulation of i2 levels meaningfully impacts drug
      bioavailability and cellular response. We also observed reduced production of
      reactive oxygen species by 30% (P < 0.05), and an enhanced expression (>1.2-fold;
      P < 0.05) of several proteins, such as hemoglobin alpha genes and superoxide
      dismutase 1, that have network functions associated with antioxidant properties.
      Interaction proteomics analysis of endogenous proteins from the cellular model,
      mainly in human intestine but also in kidney tissues, further uncovered
      interactions between i2s (but not i1s) and the antioxidant enzymes catalase and
      peroxiredoxin 1, which may influence antioxidant potential through sequestration
      of these novel partners. Our findings demonstrate for the first time dual roles
      for i2s in the cellular defense system as endogenous regulators of drug response
      as well as in oxidative stress. 

PMID- 24141016
TI  - Primary radiofrequency ablation of ventricular tachycardia early after myocardial
      infarction: evaluation in an ovine model.
AB  - BACKGROUND: Ventricular tachycardia (VT) is a significant complication of
      myocardial infarction. Radiofrequency ablation for postinfarct VT is reserved for
      drug refractory VT or VT storms. Our hypothesis is that radiofrequency ablation
      in the early postinfarct period could abolish or diminish late recurrences of VT.
      METHODS AND RESULTS: Myocardial infarct was induced by balloon occlusion of the
      left anterior descending artery in 35 sheep. The 25 survivors underwent
      programmed ventricular stimulation and electroanatomical mapping 8 days
      postinfarct. Animals with inducible VT (12 out of 25 animals) underwent immediate
      radiofrequency ablation. Further VT inductions were performed 100 and 200 days
      postinfarct. At day 8, 3.0+/-0.9 VT morphologies per animal were inducible. All
      were successfully ablated with 24+/-6 applications of radiofrequency energy. All
      had ablations on the left ventricular endocardium, and 67% had ablations on the
      right ventricular aspect of the interventricular septum. All targeted arrhythmias
      were successfully ablated acutely. One animal was euthanized because of
      hypotension from a serious pericardial effusion. The other 11 survived and
      remained arrhythmia free on subsequent inductions on the 100th and 200th days
      (P<0.001). The 13 animals without inducible VT remained noninducible at the
      subsequent studies. A historical control arm of 9 animals with inducible VT at
      day 8 remained inducible at day 100. CONCLUSIONS: Radiofrequency ablation on the
      eighth day after infarction abolished inducibility of VT at late induction
      studies <=200 days in an ovine model. Early identification and ablation of VT
      after infarction may prevent or reduce late ventricular arrhythmias but needs to
      be validated in clinical studies.

PMID- 24141017
TI  - Heat shock protein 70 protects against seizure-induced neuronal cell death in the
      hippocampus following experimental status epilepticus via inhibition of nuclear
      factor-kappaB activation-induced nitric oxide synthase II expression.
AB  - Status epilepticus induces subcellular changes that may eventually lead to
      neuronal cell death in the hippocampus. Based on an animal model of status
      epilepticus, our laboratory showed previously that sustained hippocampal seizure
      activity activates nuclear factor-kappaB (NF-kappaB) and upregulates nitric oxide
      synthase (NOS) II gene expression, leading to apoptotic neuronal cell death in
      the hippocampus. The present study examined the potential modulatory role of heat
      shock protein 70 (HSP70) on NF-kappaB signaling in the hippocampus following
      experimental status epilepticus. In Sprague-Dawley rats, kainic acid (KA) was
      microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged
      bilateral seizure activity. Expression of HSP70 was elevated as early as 1h after
      the elicitation of sustained seizure activity, followed by a progressive
      elevation that peaked at 24h. Pretreatment with an antisense oligonucleotide
      against hsp70 decreased the HSP70 expression, and significantly augmented IkappaB
      kinase (IKK) activity and phosphorylation of IkappaBalpha, alongside enhanced
      nuclear translocation and DNA binding activity of NF-kappaB in the hippocampal
      CA3 neurons and glial cells. These cellular events were followed by enhanced
      upregulation of NOS II and peroxynitrite expression 3h after sustained seizure
      activity that led to an increase of caspase-3 and DNA fragmentation in the
      hippocampal CA3 neurons 7days after experimental status epilepticus. We concluded
      that HSP70 protects against apoptotic cell death induced by NF-kappaB activation
      and NOS II-peroxynitrite signaling cascade in the hippocampal CA3 and glial cells
      following experimental status epilepticus via suppression of IKK activity and
      deactivation of IkappaBalpha. 

PMID- 24141018
TI  - Evidence that collaboration between HIF-1alpha and Notch-1 promotes neuronal cell
      death in ischemic stroke.
AB  - Recent findings suggest that Notch-1 signaling contributes to neuronal death in
      ischemic stroke, but the underlying mechanisms are unknown. Hypoxia inducible
      factor-1alpha (HIF-1alpha), a global regulator of cellular responses to hypoxia,
      can interact with Notch and modulate its signaling during hypoxic stress. Here we
      show that Notch signaling interacts with the HIF-1alpha pathway in the process of
      ischemic neuronal death. We found that a chemical inhibitor of the Notch
      activating enzyme, gamma-secretase, and a HIF-1alpha inhibitor, protect cultured
      cortical neurons against ischemic stress, and combined inhibition of Notch-1 and
      HIF-1alpha further decreased neuronal death. HIF-1alpha and Notch intracellular
      domain (NICD) are co-expressed in the neuronal nucleus, and co-immunoprecipitated
      in cultured neurons and in brain tissue from mice subjected to focal ischemic
      stroke. Overexpression of NICD and HIF-1alpha in cultured human neural cells
      enhanced cell death under ischemia-like conditions, and a HIF-1alpha inhibitor
      rescued the cells. RNA interference-mediated depletion of endogenous NICD and HIF
      1alpha also decreased cell death under ischemia-like conditions. Finally, mice
      treated with inhibitors of gamma-secretase and HIF-1alpha exhibited improved
      outcome after focal ischemic stroke, with combined treatment being superior to
      individual treatments. Additional findings suggest that the NICD and HIF-1alpha
      collaborate to engage pro-inflammatory and apoptotic signaling pathways in
      stroke. 

PMID- 24141020
TI  - Neuroprotective effects of the Sigma-1 receptor (S1R) agonist PRE-084, in a mouse
      model of motor neuron disease not linked to SOD1 mutation.
AB  - The identification of novel molecular targets crucially involved in motor neuron
      degeneration/survival is a necessary step for the development of hopefully more
      effective therapeutic strategies for amyotrophic lateral sclerosis (ALS)
      patients. In this view, S1R, an endoplasmic reticulum (ER)-resident receptor with
      chaperone-like activity, has recently attracted great interest. S1R is involved
      in several processes leading to acute and chronic neurodegeneration, including
      ALS pathology. Treatment with the S1R agonist PRE-084 improves locomotor function
      and motor neuron survival in presymptomatic and early symptomatic mutant SOD1
      G93A ALS mice. Here, we tested the efficacy of PRE-084 in a model of spontaneous
      motor neuron degeneration, the wobbler mouse (wr) as a proof of concept that S1R
      may be regarded as a key therapeutic target also for ALS cases not linked to SOD1
      mutation. Increased staining for S1R was detectable in morphologically spared
      cervical spinal cord motor neurons of wr mice both at early (6th week) and late
      (12th week) phases of clinical progression. S1R signal was also detectable in
      hypertrophic astrocytes and reactive microglia of wr mice. Chronic treatment with
      PRE-084 (three times a week, for 8weeks), starting at symptom onset,
      significantly increased the levels of BDNF in the gray matter, improved motor
      neuron survival and ameliorated paw abnormality and grip strength performance. In
      addition, the treatment significantly reduced the number of reactive astrocytes
      whereas, that of CD11b+ microglial cells was increased. A deeper evaluation of
      microglial markers revealed significant increased number of cells positive for
      the pan-macrophage marker CD68 and of CD206+ cells, involved in tissue
      restoration, in the white matter of PRE-084-treated mice. The mRNA levels of TNF
      alpha and IL-1beta were not affected by PRE-084 treatment. Thus, our results
      support pharmacological manipulation of S1R as a promising strategy to cure ALS
      and point to increased availability of growth factors and modulation of
      astrocytosis and of macrophage/microglia as part of the mechanisms involved in
      S1R-mediated neuroprotection. 

PMID- 24141021
TI  - Treatment with afobazole at delayed time points following ischemic stroke
      improves long-term functional and histological outcomes.
AB  - There is currently a significant lack of therapeutic options for acute ischemic
      stroke, and no drug has been approved for treating patients at delayed time
      points (>=6h post-stroke). Afobazole, an anxiolytic currently used clinically in
      Russia, has been shown to reduce neuronal and glial cell injury in vitro
      following ischemia. Experiments using the permanent middle cerebral artery
      occlusion (MCAO) rat model were carried out to determine if afobazole can reduce
      ischemic stroke damage in vivo and expand the therapeutic window for stroke
      treatment. Post-stroke (24h) application of afobazole (0.3-3mg/kg) significantly
      decreased infarct volume at 96h post-surgery, as determined by Fluoro-Jade and
      NeuN staining of brain sections. Moreover, afobazole helped preserve both the
      levels and normal histological distribution of myelin basic protein, indicating a
      reduction in white matter injury. A time-dependence study showed that either pre
      treatment or treatment started 6 to 48h post-stroke with the drug yields improved
      outcomes at 96h. The decrease in infarct volume produced by afobazole was blocked
      by the application of either a sigma-1 (BD 1063, 30mg/kg) or a sigma-2 (SM-21,
      1mg/kg) antagonist, indicating that both receptor subtypes are involved in the
      effects of afobazole. Treatment with afobazole starting at 24h post-stroke
      resulted in enhanced survival one month following surgery. Behavioral testing of
      animals 28-32days post-surgery using the elevated body swing and forelimb grip
      strength tests revealed that treatment with afobazole starting 24h post-stroke
      significantly reduces behavioral deficits caused by ischemic stroke. The increase
      in survival and improved functional outcomes are accompanied by a reduction in
      infarct volume, as determined by thionin staining of brain sections. Taken
      together, our data support the use of afobazole as a post-stroke pharmacological
      agent to expand the current therapeutic window. 

PMID- 24141019
TI  - Microglial derived tumor necrosis factor-alpha drives Alzheimer's disease-related
      neuronal cell cycle events.
AB  - Massive neuronal loss is a key pathological hallmark of Alzheimer's disease (AD).
      However, the mechanisms are still unclear. Here we demonstrate that
      neuroinflammation, cell autonomous to microglia, is capable of inducing neuronal
      cell cycle events (CCEs), which are toxic for terminally differentiated neurons.
      First, oligomeric amyloid-beta peptide (AbetaO)-mediated microglial activation
      induced neuronal CCEs via the tumor-necrosis factor-alpha (TNFalpha) and the c
      Jun Kinase (JNK) signaling pathway. Second, adoptive transfer of CD11b+ microglia
      from AD transgenic mice (R1.40) induced neuronal cyclin D1 expression via
      TNFalpha signaling pathway. Third, genetic deficiency of TNFalpha in R1.40 mice
      (R1.40-Tnfalpha(-/-)) failed to induce neuronal CCEs. Finally, the mitotically
      active neurons spatially co-exist with F4/80+ activated microglia in the human AD
      brain and that a portion of these neurons are apoptotic. Together our data
      suggest a cell-autonomous role of microglia, and identify TNFalpha as the
      responsible cytokine, in promoting neuronal CCEs in the pathogenesis of AD. 

PMID- 24141022
TI  - Tyrosine ameliorates heat induced delay in event related potential P300 and
      contingent negative variation.
AB  - The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the
      reduction of cognitive decline during heat exposure (HE) using event-related
      potential P300, and contingent negative variation (CNV) was evaluated. Ten
      healthy males, age 20-30years participated in the study. Volunteers received
      placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45 degrees C+30% RH). P300
      latency was significantly increased (p<0.01) during exposure with placebo, which
      was reduced significantly (p<0.01) after tyrosine supplementation. There was an
      increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in
      M100 amplitude (p<0.01) during HE with placebo, which returns to near normal
      level with the tyrosine administration. A significantly higher plasma
      norepinephrine (p<0.05), dopamine and epinephrine levels were detected in
      tyrosine supplemented group post heat exposure. HE increases the brain
      catecholamine activity thereby reduces the plasma norepinephrine and dopamine
      level leading to a reduction in cognitive performances. Tyrosine supplementation
      increases the catecholamine level and reduces the impairment of cognitive
      performance during HE. 

PMID- 24141023
TI  - PNET with neuroendocrine differentiation of the lung: Report of an unusual
      entity.
AB  - Ewing's sarcoma/primitive neuroectodermal tumor (PNET) has been the subject of
      recent reports describing morphologic variants (adamantinoma-like, large cell,
      spindle cell, sclerosing, clear cell, and vascular-like) of the most classic
      form, as well as cases displaying unusual morphologic differentiation and
      atypical immunohistochemical features. We report a case of an uncommon lung tumor
      in a 20-year-old female, morphologically and molecularly consistent with an
      Ewing's sarcoma/PNET tumor with foci of squamous differentiation, and peculiar
      expression of vimentin, high-molecular-weight keratins, p63, synaptophysin, and
      chromogranin. This case raises a challenging differential diagnostic problem with
      therapeutic implications: Should the patient be treated following the protocols
      for Ewing's sarcoma/PNET tumors or as for lung carcinoma with neuroendocrine
      features? The patient we report here was treated with neoadjuvant chemotherapy
      for Ewing's sarcoma/PNET according to Euro Ewing 99 study protocol followed by
      surgery and has no evidence of disease 15 months after the initial diagnosis.
      This highlights the importance of achieving the correct diagnosis of these
      atypical tumors using all clinical, morphological, and ancillary methods
      available to allow for their correct and timely treatment. 

PMID- 24141024
TI  - Ectopic Complete Hydatidiform Mole Presenting as an Adnexal Tumor in a
      Postmenopausal Patient.
AB  - Hydatidiform mole (HM) is rare in postmenopause, with only 7 cases reported. The
      occurrence of ectopic HM is also rare, with 26 fully documented tubal cases. We
      are not aware of any reported cases of ectopic HM in a postmenopausal patient. In
      a 51-year-old patient with 3 years amenorrhea, surgery revealed a necrotic,
      hemorrhagic mass involving the right peritubal space. Microscopically, chorionic
      villi were seen within the hemorrhagic mass accompanied by circumferential
      trophoblast hyperplasia. Immunohistochemically, p57(kip2) positive nuclei were
      prominent in the extravillous (intermediate) trophoblast. The HER2 FISH
      expression was diploid, consistent with the diagnosis of an early complete HM. 

PMID- 24141025
TI  - Gating delays for two respiratory motion sensors in scanned particle radiation
      therapy.
AB  - Gating is one option for radiotherapy of tumours that move intrafractionally due
      to respiration. Delays of the motion monitoring system can lead to a shift of the
      gating window and thus slightly shifted dose distributions. We studied the delay
      of two motion monitoring systems which use the motion of the chest wall as
      surrogate for tumour motion. Delays and their dosimetric influence were
      determined against a precise motion acquisition system in a phantom study. The
      measurement data were supplemented by dedicated simulations of the experimental
      setup. Finally, the dosimetric influence for patient treatments was estimated for
      a lung tumour case using the extreme situation of a radiosurgery setting with a
      single field. We determined delays of 132 +/- 18 ms and 103 +/- 22 ms for the two
      systems. There was no significant difference between beam start and beam stop
      delay. Even for delays of 200 ms the dosimetric influence in a single-field
      radiosurgery setting is moderate (V95 = 96.5%, V107 = 8.5%, D5-D95 = 13%). We
      conclude, that the delay of the motion monitoring system should be part of the
      commissioning process for gated treatments. The dosimetric impact should be
      studied in detail prior treatments with a scanned ion beam. 

PMID- 24141026
TI  - Topical analgesics in the management of acute and chronic pain. Introduction.

PMID- 24141027
TI  - Functional results after TME: J-pouch vs straight coloanal anastomosis and role
      of neoadjuvant radiochemotherapy.
AB  - AIM: Purpose of this study was to evaluate short and long term functional
      outcomes after TME (total mesorectal excision) for rectal cancer. The role of
      straight anastomosis or colonic J-pouch reconstruction is investigated, as well
      as the impact of preoperative chemoradiotherapy is analyzed as a cause of the so
      called "anterior resection syndrome". METHODS: We enrolled 40 patients (17 male
      and 23 female), in which a low anterior resection was performed: they were
      divided in four groups: A1 (Straight and no RCT), A2 (Straight and RCT), B1 (J
      pouch and no RCT), B2 (J-pouch and RCT). Follow-up was performed six and twelve
      months after surgery, through a clinical questionnaire ( to assess: stool
      frequency, incomplete emptying, the presence of fecal leakage, urgency and
      incontinence ) and through anorectal manometry ( to assess rest pressure, squeeze
      pressure, max tolerated volume and compliance). Results were evaluated through T
      Student and Chi-Squared test. RESULTS: Six months after surgery, colonic J-pouch
      offers the best clinical and functional results, in both radiated and not
      radiated patients (except for incomplete emptying); in the straight group,
      however, there is an improvement of results after twelve months. Chemoradiation
      therapy is always associated with worse functional results. DISCUSSION: RCT seems
      to invalidate J-pouch function in particular, in fact twelve months after surgery
      the difference between J-Pouch and Straight groups is not statistically different
      for most of the parameters. CONCLUSION: J-pouch gives a real functional advantage
      for only six months after surgery, especially in patients treated with neoajuvant
      chemoradiation therapy.

PMID- 24141028
TI  - Overexpression of constitutively active OsCPK10 increases Arabidopsis resistance
      against Pseudomonas syringae pv. tomato and rice resistance against Magnaporthe
      grisea.
AB  - Calcium-dependent protein kinases (CDPKs) are crucial calcium sensors involved in
      plant responses to pathogen infection. Here, we report isolation and functional
      characterization of the pathogen-responsive rice OsCPK10 gene. The expression of
      OsCPK10 was strongly induced following treatment with a Magnaporthe grisea
      elicitor. Kinase activity assay showed that the functional OsCPK10 protein not
      only autophosphorylated, but also phosphorylated Casein in a calcium-dependent
      manner. Overexpression of constitutively active OsCPK10 in Arabidopsis enhanced
      the resistance to infection with Pseudomonas syringae pv. tomato, associated with
      elevated expression of both SA- and JA-related defense genes. Similarly,
      transgenic rice plants containing constitutively active OsCPK10 exhibited
      enhanced resistance to blast fungus M. grisea. The enhanced resistance in the
      transgenic lines was associated with activated expression of SA- and JA-related
      defense genes. Collectively, our results indicate that rice OsCPK10 is a crucial
      regulator in plant immune responses, and that it may regulate disease resistance
      by activating both SA- and JA-dependent defense responses. 

PMID- 24141029
TI  - The role of catechol-O-methyltransferase in catechol-enhanced erythroid
      differentiation of K562 cells.
AB  - Catechol is widely used in pharmaceutical and chemical industries. Catechol is
      also one of phenolic metabolites of benzene in vivo. Our previous study showed
      that catechol improved erythroid differentiation potency of K562 cells, which was
      associated with decreased DNA methylation in erythroid specific genes. Catechol
      is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation.
      In the present study, the role of COMT in catechol-enhanced erythroid
      differentiation of K562 cells was investigated. Benzidine staining showed that
      exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced
      mRNA expression of erythroid specific genes in K562 cells. Treatment with
      catechol caused a time- and concentration-dependent increase in guaiacol
      concentration in the medium of cultured K562 cells. When COMT expression was
      knocked down by COMT shRNA expression in K562 cells, the production of guaiacol
      significantly reduced, and the sensitivity of K562 cells to cytotoxicity of
      catechol significantly increased. Knockdown of COMT expression by COMT shRNA
      expression also eliminated catechol-enhanced erythroid differentiation of K562
      cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine
      or its demethylated product S-adenosyl-L-homocysteine induced a significant
      increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of
      erythroid specific genes. These findings indicated that O-methylation catalyzed
      by COMT acted as detoxication of catechol and involved in catechol-enhanced
      erythroid differentiation of K562 cells, and the production of S-adenosyl-L
      homocysteine partly explained catechol-enhanced erythroid differentiation.

PMID- 24141030
TI  - Temporal and spatial features of the formation of DNA adducts in sulfur mustard
      exposed skin.
AB  - Sulfur mustard (SM) is a chemical warfare agent that targets skin where it
      induces large blisters. DNA alkylation is a critical step to explain SM-induced
      cutaneous symptoms. We determined the kinetics of formation of main SM-DNA
      adducts and compare it with the development of the SM-induced pathogenesis in
      skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was
      biopsied between 6h and 21 days. Formation of SM DNA adducts was dose-dependent
      with a maximum immediately after exposure. However, adducts were persistent and
      still detectable 21 days post-exposure. The time-dependent formation of DNA
      adducts was also found to be correlated with the appearance of apoptotic cells.
      This temporal correlation suggests that these two early events are responsible
      for the severity of the damage to the skin. Besides, SM-DNA adducts were also
      detected in areas located next to contaminated zone, thus suggesting that SM
      diffuses in skin. Altogether, this work provides for the first time a clear
      picture of SM-induced genotoxicity using DNA adducts as a marker.

PMID- 24141031
TI  - Comparative pathophysiology, toxicology, and human cancer risk assessment of
      pharmaceutical-induced hibernoma.
AB  - In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue
      (BAT) that typically occurs at subcutaneous locations and is successfully treated
      by surgical excision. No single cause has been accepted to explain these very
      rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often
      malignant, usually occurs in the thoracic or abdominal cavity, and metastases are
      common. In recent years, there has been an increased incidence of spontaneous
      hibernomas in rat carcinogenicity studies, but overall the occurrence remains
      relatively low and highly variable across studies. There have only been four
      reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity
      studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline,
      a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and
      hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may
      contribute to the pathogenesis of BAT activation/proliferation and/or subsequent
      hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic
      stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism,
      and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of
      Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of
      hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical
      therapeutics and its relevance to human safety risk assessment is complex. One
      should consider: the genotoxicity of the test article, dose/exposure and safety
      margins, and pathophysiologic and morphologic differences and similarities of
      hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity
      studies of pharmaceutical agents do not appear to be relevant for human risk at
      therapeutic dosages. 

PMID- 24141033
TI  - Low intensity conduction states in FeS2: implications for absorption, open
      circuit voltage and surface recombination.
AB  - Pyrite (FeS2), being a promising material for future solar technologies, has so
      far exhibited in experiments an open-circuit voltage (OCV) of around 0.2 V, which
      is much lower than the frequently quoted 'accepted' value for the fundamental
      bandgap of ~0.95 eV. Absorption experiments show large subgap absorption,
      commonly attributed to defects or structural disorder. However, computations
      using density functional theory with a semi-local functional predict that the
      bottom of the conduction band consists of a very low intensity sulfur p-band that
      may be easily overlooked in experiments because of the high intensity onset that
      appears 0.5 eV higher in energy. The intensity of absorption into the sulfur p
      band is found to be of the same magnitude as contributions from defects and
      disorder. Our findings suggest the need to re-examine the value of the
      fundamental bandgap of pyrite presently in use in the literature. If the
      contribution from the p-band has so far been overlooked, the substantially
      lowered bandgap would partly explain the discrepancy with the OCV. Furthermore,
      we show that more states appear on the surface within the low energy sulfur p
      band, which suggests a mechanism of thermalization into those states that would
      further prevent extracting electrons at higher energy levels through the surface.
      Finally, we speculate on whether misidentified states at the conduction band
      onset may be present in other materials. 

PMID- 24141032
TI  - COUP-TFII inhibits NFkappaB activation in endocrine-resistant breast cancer
      cells.
AB  - Reduced COUP-TFII expression contributes to endocrine resistance in breast cancer
      cells. Endocrine-resistant breast cancer cells have higher NFkappa B (NFkappaB)
      activity and target gene expression. The goal of this study was to determine if
      COUP-TFII modulates NFkappaB activity. Endocrine-resistant LCC9 cells with low
      endogenous COUP-TFII displayed ~5-fold higher basal NFkappaB activity than
      parental endocrine-sensitive MCF-7 breast cancer cells. Transient transfection of
      LCC9 cells with COUP-TFII inhibited NFkappaB activation and reduced NFkappaB
      target gene expression. COUP-TFII and NFkappaB were inversely correlated in
      breast cancer patient samples. Endogenous COUP-TFII coimmunoprecipitated with
      NFkappaB subunits RelB and NFkappaB1 in MCF-7 cells. COUP-TFII inhibited NFkappaB
      DNA binding in vitro and impaired coactivator induced NFkappaB transactivation.
      LCC9 cells were growth-inhibited by an NFkappaB inhibitor and 4-hydroxytamoxifen
      compared to MCF-7 cells. Together these data indicate a novel role for COUP-TFII
      in suppression of NFkappaB activity and explain, in part, why decreased COUP-TFII
      expression results in an endocrine-resistant phenotype. 

PMID- 24141034
TI  - Goal neglect and knowledge chunking in the construction of novel behaviour.
AB  - Task complexity is critical in cognitive efficiency and fluid intelligence. To
      examine functional limits in task complexity, we examine the phenomenon of goal
      neglect, where participants with low fluid intelligence fail to follow task rules
      that they otherwise understand. Though neglect is known to increase with task
      complexity, here we show that - in contrast to previous accounts - the critical
      factor is not the total complexity of all task rules. Instead, when the space of
      task requirements can be divided into separate sub-parts, neglect is controlled
      by the complexity of each component part. The data also show that neglect
      develops and stabilizes over the first few performance trials, i.e. as
      instructions are first used to generate behaviour. In all complex behaviour, a
      critical process is combination of task events with retrieved task requirements
      to create focused attentional episodes dealing with each decision in turn. In
      large part, we suggest, fluid intelligence may reflect this process of converting
      complex requirements into effective attentional episodes. 

PMID- 24141035
TI  - Degrading phonetic information affects matching of audiovisual speech in adults,
      but not in infants.
AB  - Infants and adults are well able to match auditory and visual speech, but the
      cues on which they rely (viz. temporal, phonetic and energetic correspondence in
      the auditory and visual speech streams) may differ. Here we assessed the relative
      contribution of the different cues using sine-wave speech (SWS). Adults (N=52)
      and infants (N=34, age ranged in between 5 and 15months) matched 2 trisyllabic
      speech sounds ('kalisu' and 'mufapi'), either natural or SWS, with visual speech
      information. On each trial, adults saw two articulating faces and matched a sound
      to one of these, while infants were presented the same stimuli in a preferential
      looking paradigm. Adults' performance was almost flawless with natural speech,
      but was significantly less accurate with SWS. In contrast, infants matched the
      sound to the articulating face equally well for natural speech and SWS. These
      results suggest that infants rely to a lesser extent on phonetic cues than adults
      do to match audio to visual speech. This is in line with the notion that the
      ability to extract phonetic information from the visual signal increases during
      development, and suggests that phonetic knowledge might not be the basis for
      early audiovisual correspondence detection in speech. 

PMID- 24141036
TI  - Denosumab compared with risedronate in postmenopausal women suboptimally adherent
      to alendronate therapy: efficacy and safety results from a randomized open-label
      study.
AB  - Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures
      in postmenopausal women with osteoporosis. In subjects who were treatment-naive
      or previously treated with alendronate, denosumab was associated with greater
      gains in bone mineral density (BMD) and decreases in bone turnover markers when
      compared with alendronate-treated subjects. This trial was designed to compare
      the efficacy and safety of denosumab with risedronate over 12 months in
      postmenopausal women who transitioned from daily or weekly alendronate treatment
      and were considered to be suboptimally adherent to therapy. In this randomized,
      open-label study, postmenopausal women aged >=55 years received denosumab 60 mg
      subcutaneously every 6 months or risedronate 150 mg orally every month for 12
      months. Endpoints included percentage change from baseline in total hip BMD
      (primary endpoint), femoral neck, and lumbar spine BMD at month 12, and
      percentage change from baseline in sCTX-1 at months 1 and 6. Safety was also
      assessed. A total of 870 subjects were randomized (435, risedronate; 435,
      denosumab) who had a mean (SD) age of 67.7 (6.9) years, mean (SD) BMD T-scores of
      -1.6 (0.9), -1.9 (0.7), and -2.2 (1.2) at the total hip, femoral neck, and lumbar
      spine, respectively, and median sCTX-1 of 0.3 ng/mL at baseline. At month 12,
      denosumab significantly increased BMD compared with risedronate at the total hip
      (2.0% vs 0.5%), femoral neck (1.4% vs 0%), and lumbar spine (3.4% vs 1.1%;
      p<0.0001 at all sites). Denosumab significantly decreased sCTX-1 compared with
      risedronate at month 1 (median change from baseline of -78% vs -17%; p<0.0001)
      and month 6 (-61% vs -23%; p<0.0001). Overall and serious adverse events were
      similar between groups. In postmenopausal women who were suboptimally adherent to
      alendronate therapy, transitioning to denosumab was well tolerated and more
      effective than risedronate in increasing BMD and reducing bone turnover.

PMID- 24141037
TI  - Pairing behavior and reproduction in Hyalella azteca as sensitive endpoints for
      detecting long-term consequences of pesticide pulses.
AB  - The aim of the present study was to examine acute and delayed effects of pulse
      exposure of the pyrethroid pesticide, permethrin, on precopulatory pairs of
      Hyalella azteca. Pairs of H. azteca were exposed to a single 1h pulse of
      different nominal concentrations of permethrin: 0, 0.3, 0.9 or 2.7 MUg/L. During
      exposure, pairing behavior was observed, and during a 56 day post-exposure period
      the treatments were monitored for pairing behavior, survival and reproductive
      output. All permethrin-exposed pairs separated within minutes during exposure and
      shortly thereafter became immobile; however they regained mobility after transfer
      to clean water. The time to re-form pairs was significantly longer in all tested
      concentrations compared to the control, although all surviving pairs re-formed
      within the 56 day test period. Nevertheless not all pairs exposed to 0.9 and 2.7
      MUg/L reproduced. Furthermore the numbers of juveniles produced by pairs exposed
      to 0.9 and 2.7 MUg/L, but not 0.3 MUg/L, were lower throughout the entire post
      exposure period compared to the control groups, and the total numbers of
      juveniles produced during 56 days were significantly lower in organisms exposed
      to 0.9 and 2.7 MUg/L, but not 0.3 MUg/L, compared to the control groups. The long
      term effects of short-term exposure on reproductive behavior of pairs could
      potentially have consequences for the population dynamics of H. azteca. However,
      since individual-level responses can both overestimate and underestimate effects
      at the population level, appropriate population models are needed to reduce the
      uncertainty in extrapolating between these levels of biological organization.

PMID- 24141038
TI  - Multigenerational demographic responses of sexual and asexual Artemia to chronic
      genotoxicity by a reference mutagen.
AB  - Genotoxins are capable of multigenerational impacts on natural populations via
      DNA damage and mutations. Sexual reproduction is assumed to reduce the long term
      consequences of genotoxicity for individual fitness and should therefore reduce
      population level effects. However, rather few empirical studies have quantified
      the magnitude of this effect. We tried to analyse the multigenerational
      demographic responses of sexual Artemia franciscana and asexual Artemia
      parthenogenetica due to chronic genotoxicity by a reference mutagen, ethyl
      methane sulfonate (EMS). A prospective (elasticity analysis) and retrospective
      (differences and contributions) perturbation analysis was carried out to
      understand the interactions of life history traits with population growth rate
      lambda by comparing elasticities, differences and contributions of vital rates to
      lambda. None of the previous studies have compared the effects of chronic
      genotoxicity using prospective and retrospective perturbation analyses in a
      sexual and asexual species over generations. The behaviour of a population with
      lower growth rate in the presence of genotoxicants in the field was studied by
      simulating reduced fertilities in the LTRE design. The results of prospective and
      retrospective perturbation analyses of effects on lambda showed that population
      growth rate was proportionally more sensitive to juvenile survival whereas the
      effect of EMS on juvenile fertility contributed more to the variations in
      population growth rate in both the species and this effect was due to the high
      growth rate of Artemia. Simulations of lower population growth rate in the model
      showed that adult fertility and survival are also of importance. Sexual
      reproduction substantially mitigated the long term consequences of genetic
      damage, although these would be greater if population growth rate were lower. So
      multigenerational population level consequences of genotoxicity were much greater
      in an asexual species. So asexual species, and those with a parthenogenetic phase
      in their life cycle, may be particularly vulnerable to the effects of
      environmental mutagens. Ecological risk assessments should include information
      from multigenerational studies, as responses to genotoxicity may vary depending
      on the life history strategies and reproductive modes of the species under
      consideration. Single generation studies may under or over-estimate risks. 

PMID- 24141039
TI  - Chronic cholestatic liver diseases: clues from histopathology for pathogenesis.
AB  - Chronic cholestatic liver diseases include fibrosing cholangiopathies such as
      primary biliary cirrhosis or primary sclerosing cholangitis. These and related
      cholangiopathies clearly display pathologies associated with (auto)immunologic
      processes. As the cholangiocyte's apical membrane is exposed to the toxic actions
      of the bile fluid, the interaction of bile with cholangiocytes and the biliary
      tree in general must be considered to completely understand the pathogenesis of
      cholangiopathies. While the molecular processes involved in the hepatocellular
      formation of bile are well understood in both normal and pathophysiologic
      conditions, those in the bile ducts of normal liver and in livers with
      cholangiopathies lag behind. This survey highlights key mechanisms known to date
      that are important for the formation of bile by hepatocytes and its modification
      by the biliary tree. It also delineates the clinical pathophysiologic findings
      for cholangiopathies and puts them in perspective with current experimental
      models to reveal the pathogenesis of cholangiopathies and develop novel
      therapeutic approaches. 

PMID- 24141040
TI  - Stereoselective analysis of nebivolol isomers in human plasma by high-performance
      liquid chromatography-tandem mass spectrometry: application in pharmacokinetics.
AB  - Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol
      (SRRR) is a beta1 adrenergic receptor blocker and its antipode, l-nebivolol
      (RSSS) is responsible for endothelium-dependent NO liberation. This report
      describes the development and validation of a method of analysis of nebivolol
      isomers in human plasma by high-performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Nebivolol isomers were extracted from 2mL aliquots of
      plasma spiked with tramadol as internal standard, alkalinized and added of sodium
      chloride and diisopropyl ether:dichloromethane (70:30, v/v). Nebivolol isomers
      were resolved on a Chirobiotic((r)) V column using methanol:acetic
      acid:diethylamine (100:0.15:0.05, v/v/v) as mobile phase. Protonated ion and
      respective ion product were monitored in transitions 406>151 for nebivolol and
      264>58 for internal standard tramadol. There was no racemization of nebivolol
      isomers during the procedures of sample preparation and chromatographic analysis
      and matrix effect was absent. Analysis of nebivolol isomers showed linearity for
      plasma concentrations of 25-2500pg/mL of each isomer. The quantification limit
      was 25pg of each isomer/mL of plasma. Variation coefficients and inaccuracy
      calculated in precision and accuracy determinations were lower than 15%.
      Nebivolol was stable in human plasma after three successive cycles of freezing
      and thawing, during 4h at room temperature and after processing during 12h in the
      auto sampler at 5 degrees C showing deviation values lower than 15%. The method
      was applied in a study of the kinetic disposition of nebivolol in plasma samples
      collected until 48h after administration of an oral single dose of 10mg of
      racemic nebivolol hydrochloride to a patient with systemic arterial hypertension.
      The clinical study demonstrated that the nebivolol pharmacokinetics is
      stereoselective. Isomer l-nebivolol showed higher AUC(0-infinity) (9.4ng/h/mL vs.
      4.7ng/h/mL) and smaller apparent clearance (Cl/f) (531.8L/h vs. 1304.4L/h) when
      compared to antipode d-nebivolol. 

PMID- 24141041
TI  - Simultaneous determination of selected chemotherapeutics in human whole blood by
      molecularly imprinted polymers coated solid phase microextraction fibers and
      liquid chromatography-tandem mass spectrometry.
AB  - Development and validation of novel, general liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for the simultaneous determination of amoxicillin
      (AMOX), cefatoxime (CEF), ciprofloxacin (CIP), daptomycin (DAPTO), fluconazole
      (FLU), gentamicin (GEN), clindamycin (KLI), linezolid (LIN), metronidazole (MET),
      moxifloxacin (MOXI) in human whole blood are described. Samples were prepared on
      solid phase microextraction way with the use of polymeric sorption coatings with
      molecular imprints and analyzed using a gradient separation over an ACE C18
      column (4.6mm*150mm, 3MUm) with isocratic elution. Positive electrospray
      ionization was employed as the ionization source. The mobile phase consisted of
      acetonitrile-water (0.1% formic acid or 5mM ammonium acetate) at a flow
      0.4ml/min. The chromatographic run time was kept less than 9min. The intra- and
      inter-day relative standard deviation across three validation runs over the
      entire concentration range was less than 7.3%, while the accuracy was within +/
      8.4%. The mean recovery of all the analytes ranged from 65.0 to 83.0%. This
      method was successfully applied to clinical samples from patients with clinically
      diagnosed bacterial infections process. 

PMID- 24141042
TI  - Identification of acteoside and its major metabolites in rat urine by ultra
      performance liquid chromatography combined with electrospray ionization
      quadrupole time-of-flight tandem mass spectrometry.
AB  - In this study, metabolites in the urine samples of rats orally administered with
      acteoside, a phenylethanoid glycoside compound, were detected and identified
      using ultra-performance liquid chromatography coupled with electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS)
      combined with an automated MS(E) technique. Up to 35 metabolites (19 metabolites
      of the parent drug and 16 metabolites of the degradation products) were observed,
      including processes of oxidization, glucuronidation, sulfation, and methyl
      conjugation. According to the metabolic pathways, acteoside mainly functioned as
      a prodrug and underwent hydrolysis before being absorbed into the blood. The
      degradation products, especially caffeic acid and hydroxytyrosol, were involved
      in further metabolism which was responsible for the low oral bioavailability but
      obvious pharmacological activities of acteoside. In summary, this work provided
      valuable information on acteoside metabolism through the rapid and reliable
      UPLC/ESI-QTOF-MS technique, which could be widely used for the investigation of
      natural product metabolites. 

PMID- 24141043
TI  - Simultaneous ligand fishing and identification of human serum albumin binders
      from Eucommia ulmoides bark using surface plasmon resonance-high performance
      liquid chromatography-tandem mass spectrometry.
AB  - Eucommia ulmoides bark has long been known as tonic herb, however, the systematic
      biochemical fingerprint analysis and corresponding structural identification are
      inadequate so far. Here we describe on-line surface plasmon resonance-high
      performance liquid chromatography-tandem mass spectrometry (SPR-HPLC-MS/MS) to
      fish out and identify human serum albumin (HSA) binders from E. ulmoides bark. A
      total of 22 HSA binders, including 4 iridoids, 11 lignans, 3 flavonoids and 4
      phenolic acids, were identified or tentatively characterized based on their
      retention times, UV spectra and MS/MS spectrum with references or literature
      data, among which, geniposidic acid, geniposide and chlorogenic acid were the
      predominant HSA binders. In addition, the major characteristic fragmentation
      pathways of iridoids and lignans were investigated. The higher reusability and
      stability of the immobilized HSA allow the method cost-effective and high
      throughput. Compared with conventional HPLC-MS/MS for chemical fingerprint
      analysis, SPR-HPLC-MS/MS is simple and easy to provide biochemical fingerprint,
      moreover, it is easy to identify low-content HSA binders because of the sample
      clean-up/concentration procedure. 

PMID- 24141044
TI  - Purification of hepatitis B surface antigen virus-like particles from recombinant
      Pichia pastoris and in vivo analysis of their immunogenic properties.
AB  - Following earlier studies on high-level intracellular production of hepatitis B
      surface antigen (HBsAg) using recombinant Pichia pastoris, we present here in
      detail an enhanced method for the purification of recombinant HBsAg virus-like
      particles (VLPs). We have screened various detergents for their ability to
      promote the solubilization of recombinant intracellular HBsAg. In addition, we
      have analyzed the effect of cell disruption and extraction regarding their impact
      on the release of HBsAg. Our results show that introduction of the mild nonionic
      detergent Tween 20 in the initial process of cell lysis at ~600bars by high
      pressure homogenization leads to the best results. The subsequent purification
      steps involved polyethylene glycol precipitation of host cell contaminants,
      hydrophobic adsorption of HBsAg to colloidal silica followed by ion-exchange
      chromatography and either isopycnic density ultracentrifugation or size exclusion
      chromatography for the recovery of the VLPs. After final KSCN treatment and
      dialysis, a total yield of ~3% with a purity of >99% was reached. The pure
      protein was characterized by electron microscopy, showing the presence of uniform
      VLPs which are the pre-requisite for immunogenicity. The intramuscular co
      administration of HBsAg VLPs, with either alum or a PEGylated-derivative of the
      toll-like receptor 2/6 agonist MALP-2, to mice resulted in the elicitation of
      significantly higher HBsAg-specific IgG titers as well as a stronger cellular
      immune response compared to mice vaccinated with a gold standard vaccine
      (EngerixTM). These results show that P. pastoris derived HBsAg VLPs exhibit a
      high potential as a superior biosimilar vaccine against hepatitis B. 

PMID- 24141046
TI  - Atomic order and cluster energetics of a 17 wt% Si-based glass versus the liquid
      phase.
AB  - Aerodynamic levitation of a multicomponent 17 wt% Si glass formed by rapid
      quenching of the melt phase was studied by high resolution x-ray diffraction
      (XRD) and reverse Monte Carlo (RMC) modelling. The main local atomic order
      features comprised interactions between Si, Fe and Mg polyhedra, the
      stereochemistry of which was on a par with the literature. Both the glass and the
      liquid state appeared to consist of the same fundamental Si-O, Fe-O and Mg-O
      clusters, with only the relative number of each varying between the two.
      Transition from liquid to glass involved a three-fold decrease in uncoordinated O
      (to within the first minimum of the total g(r)) and a marked increase of Fe-Si-Mg
      polyhedra bridging O. Octahedral Fe coordination was not suggested by the RMC
      data. All-electron open-shell density functional theory (DFT) calculations of the
      most prominent clusters suggested independence between the Fe oxidation state and
      its polyhedra O-coordination. Of secondary thermodynamic importance were
      indications of network-forming Fe(2+) and Fe(3+) distorted trigonal and
      tetrahedral polyhedra. In all occasions, the Fe ferrous and ferric states
      involved comparable binding energies within similar clusters which indicate a
      dynamic equilibrium between the two.

PMID- 24141045
TI  - The ionic liquid isopropylammonium formate as a mobile phase modifier to improve
      protein stability during reversed phase liquid chromatography.
AB  - The room temperature ionic liquid isopropylammonium formate (IPAF) is studied as
      a reversed phase HPLC mobile phase modifier for separation of native proteins
      using a polymeric column and the protein stability is compared to that using
      acetonitrile (MeCN) as the standard organic mobile phase modifier. A variety of
      important proteins with different numbers of subunits are investigated, including
      non-subunit proteins: albumin, and amyloglucosidase (AMY); a two subunit protein:
      thyroglobulin (THY); and four subunit proteins: glutamate dehydrogenase (GDH) and
      lactate dehydrogenase (LDH). A significant enhancement in protein stability is
      observed in the chromatograms upon using IPAF as a mobile phase modifier. The
      first sharper peak at about 2min represented protein in primarily the native form
      and a second broader peak more retained at about 5-6min represented substantially
      denatured or possibly aggregated protein. The investigated proteins (except LDH)
      could maintain the native form within up to 50% IPAF, while a mobile phase, with
      as low as 10% MeCN, induced protein denaturation. The assay for pyruvate using
      LDH has further shown that enzymatic activity can be maintained up to 30% IPAF in
      water in contrast to no activity using 30% MeCN. 

PMID- 24141047
TI  - Do sex hormones influence emotional modulation of pain and nociception in healthy
      women?
AB  - Sex hormones may contribute to inter- and intra-individual differences in pain by
      influencing emotional modulation of pain and nociception. To study this, a well
      validated picture-viewing paradigm was used to assess emotional modulation of
      pain and the nociceptive flexion reflex (NFR; physiologic measure of nociception)
      during mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle
      in healthy normally cycling women (n=40). Salivary estradiol, progesterone, and
      testosterone were assessed at each testing session. Emotional modulation of
      pain/NFR did not differ across menstrual phases, but low estradiol was associated
      with weaker emotional modulation of NFR (during all phases) and emotional
      modulation of pain (ovulatory and late-luteal phases). Given evidence that a
      failure to emotionally modulate pain might be a risk factor for chronic pain, low
      estradiol may promote chronic pain via this mechanism. However, future research
      is needed to extend these findings to women with disturbances of pain, emotion,
      and/or sex hormones. 

PMID- 24141049
TI  - Identification of MMP-2 as a novel enhancer of cerebellar granule cell
      proliferation.
AB  - During the first postnatal days in the mouse, granule cells (GCs) undergo massive
      proliferation, which then gradually decreases. Matrix metalloproteinase-2 (MMP
      2), a Zn(2+)-dependent proteolytic enzyme, is involved in a wide variety of
      pathological and physiological pathways. Evidence for a role of this proteinase
      in cell proliferation is emerging, reporting its involvement in pathological
      proliferation, as well as during neurogenesis and developmental proliferation of
      non-CNS tissues. In this study, MMP-2 protein expression was observed within the
      early postnatal cerebellar cortex, predominantly in Purkinje cells and within the
      GC proliferative zone, i.e. the superficial external granular layer (EGL).
      Consistently, the spatiotemporal MMP-2 mRNA and protein profiles highly
      correlated with the peak of GC precursor (GCP) proliferation and detailed
      morphometric analyses of MMP-2 deficient cerebella revealed a thinner EGL due to
      a decreased GCP proliferation. BrdU cumulative experiments, performed to measure
      the length of different cell cycle phases, further disclosed a transiently
      prolonged S-phase in MMP-2 deficient GCPs during early cerebellar development. In
      consequence, MMP-2 deficient animals displayed a transient delay in GC migration
      towards the IGL. In conclusion, our findings provide important evidence for a
      role for MMP-2 in neuronal proliferation and cell cycle kinetics in the
      developing CNS. 

PMID- 24141048
TI  - HspB1 silences translation of PDZ-RhoGEF by enhancing miR-20a and miR-128
      expression to promote neurite extension.
AB  - HspB1 is a small heat shock protein implicated in neuronal survival and neurite
      growth; mutations in HspB1 have been identified in hereditary motor
      neuronopathies and Charcot Marie Tooth Type 2 neuropathies. In cortical neurons
      we found that expression of HspB1 decreased RhoA activity and RhoA-GTP protein,
      and reversed the inhibition of neurite extension induced by NogoA. HspB1
      decreased PDZ-RhoGEF, a RhoA specific guanine nucleotide exchange factor, while
      other regulators of RhoA activity were unchanged. The decrease in PDZ-RhoGEF was
      independent of proteasomal or lysosomal degradation pathways and was not
      associated with changes in PDZ-RhoGEF mRNA. We sequenced the 3'UTR of rat PDZ
      RhoGEF and found binding sites for miRNAs miR-20a, miR-128 and miR-132.
      Expression of these microRNAs was substantially increased in cortical neurons
      transfected with HspB1. Co-transfection of HspB1 with specific inhibitors of miR
      20a or miR-128 prevented the decrease in PDZ-RhoGEF and blocked the neurite
      growth promoting effects of HspB1. Using the 3'UTR of PDZ-RhoGEF mRNA in a
      luciferase reporter construct we observed that HspB1, miR-20a and miR-128 each
      inhibited luciferase expression. We conclude that HspB1 regulates RhoA activity
      through modulation of PDZ-RhoGEF levels achieved by translational control through
      enhanced expression of specific miRNAs (miR-20a and miR-128). Regulation of RhoA
      activity by translational silencing of PDZ-RhoGEF may be the mechanism through
      which HspB1 is involved in regulation of neurite growth. As RhoA-GTPase plays a
      regulatory role in the organization and stability of cytoskeletal networks
      through its downstream effectors, the results suggest a possible mechanism
      linking HspB1 mutations and axonal cytoskeletal pathology. 

PMID- 24141051
TI  - p21-Activated kinase (PAK) is required for Bone Morphogenetic Protein (BMP)
      induced dendritogenesis in cortical neurons.
AB  - Bone Morphogenetic Proteins (BMPs) are crucial for many aspects of the
      development and differentiation of the nervous system and are important in
      controlling cytoskeletal remodeling during neuronal morphogenesis. BMPs are
      TGFbeta superfamily members that signal through a heteromeric complex of type I
      and type II BMP receptors. The BMPRII receptor is particularly important in
      mediating remodeling of the neuronal cytoskeleton through the activation of
      BMPRII-bound cytoskeletal regulators, such as LIM Kinase (LIMK). Here, we show
      that PAK1, a key regulator of diverse neuronal processes and an upstream
      activator of LIMK, binds to the BMP type I receptor, ALK2. Although, PAK1 is
      dispensable for activation of the Smad transcriptional mediators, abrogation of
      PAK1 expression or inhibition of PAK1 activity prevents BMP-induced neurite
      outgrowth in cultured neuroblastoma cell lines. Moreover, in primary murine
      embryonic cortical neurons, inhibition of PAK activity blocks BMP7-induced
      cofilin phosphorylation, prevents remodeling of the actin cytoskeleton and
      thereby blocks BMP7-induced dendrite formation. Thus, we propose a model in which
      BMP7 signaling leads to the recruitment of ALK2-bound PAK1 to BMPRII, which binds
      a downstream regulator of the actin cytoskeleton, LIMK1, and that the BMP
      receptor complex thereby acts as a scaffold to localize and coordinate actin
      cytoskeletal remodeling. We propose that this scaffold plays a key role in
      mediating BMP7-dependent dendritogenesis in primary cortical neurons. 

PMID- 24141052
TI  - Elevation of lutein content in tomato: a biochemical tug-of-war between lycopene
      cyclases.
AB  - Lutein is becoming increasingly important in preventive medicine due to its
      possible role in maintaining good vision and in preventing age-related
      maculopathy. Average daily lutein intake in developed countries is often below
      suggested daily consumption levels, and lutein supplementation could be
      beneficial. Lutein is also valuable in the food and feed industries and is
      emerging in nutraceutical and pharmaceutical markets. Currently, lutein is
      obtained at high cost from marigold petals, and synthesis alternatives are thus
      desirable. Tomato constitutes a promising starting system for production as it
      naturally accumulates high levels of lycopene. To develop tomato for lutein
      synthesis, the tomato Red Setter cultivar was transformed with the tomato
      lycopene epsilon-cyclase-encoding gene under the control of a constitutive
      promoter, and the HighDelta (HD) line, characterised by elevated lutein and delta
      carotene content in ripe fruits, was selected. HD was crossed to the transgenic
      HC line and to RS(B) with the aim of converting all residual fruit delta-carotene
      to lutein. Fruits of both crosses were enriched in lutein and presented unusual
      carotenoid profiles. The unique genetic background of the crosses used in this
      study permitted an unprecedented analysis of the role and regulation of the
      lycopene cyclase enzymes in tomato. A new defined biochemical index, the relative
      cyclase activity ratio, was used to discern post-transcriptional regulation of
      cyclases, and will help in the study of carotenoid biosynthesis in photosynthetic
      plant species and particularly in those, like tomato, that have been domesticated
      for the production of food, feed or useful by-products. 

PMID- 24141050
TI  - UCP2 overexpression worsens mitochondrial dysfunction and accelerates disease
      progression in a mouse model of amyotrophic lateral sclerosis.
AB  - Mitochondrial dysfunction leading to deficits in energy production, Ca(2+) uptake
      capacity, and free radical generation has been implicated in the pathogenesis of
      familial amyotrophic lateral sclerosis (ALS) caused by mutations in Cu,Zn
      superoxide dismutase (SOD1). Numerous studies link UCP2, a member of the
      uncoupling protein family, to protection of neurons from mitochondrial
      dysfunction and oxidative damage in various mouse models of acute stress and
      neurodegeneration, including Parkinson's disease. Here, we tested the potential
      neuroprotective effects of UCP2 and its ability to modulate mitochondrial
      function, in the G93A mutant SOD1 mouse model of familial ALS. Disease phenotype,
      mitochondrial bioenergetics, and Ca(2+) uptake capacity were investigated in the
      central nervous system of double transgenic mice, expressing both human mutant
      G93A SOD1 and human UCP2 (hUCP2). Unexpectedly, hUCP2 expression accelerated the
      disease course of SOD1 mutant mice. In addition, we did not observe a classical
      uncoupling effect of hUCP2 in G93A brain mitochondria, although we did detect a
      decrease in reactive oxygen species (ROS) production from mitochondria challenged
      with the respiratory chain inhibitors rotenone and antimycin A. We also found
      that mitochondrial Ca(2+) uptake capacity was decreased in the double transgenic
      mice, as compared to G93A mice. In summary, our results indicate that the
      neuroprotective role of UCP2 in neurodegeneration is disease-specific and that,
      while a mild uncoupling by UCP2 in brain mitochondria may protect against
      neurodegeneration in some injury paradigms, the mitochondrial damage and the
      disease caused by mutant SOD1 cannot be ameliorated by UCP2 overexpression. 

PMID- 24141053
TI  - Production of medium chain length fatty alcohols from glucose in Escherichia
      coli.
AB  - Metabolic engineering offers the opportunity to produce a wide range of commodity
      chemicals that are currently derived from petroleum or other non-renewable
      resources. Microbial synthesis of fatty alcohols is an attractive process because
      it can control the distribution of chain lengths and utilize low cost
      fermentation substrates. Specifically, primary alcohols with chain lengths of 12
      to 14 carbons have many uses in the production of detergents, surfactants, and
      personal care products. The current challenge is to produce these compounds at
      titers and yields that would make them economically competitive. Here, we
      demonstrate a metabolic engineering strategy for producing fatty alcohols from
      glucose. To produce a high level of 1-dodecanol and 1-tetradecanol, an acyl-ACP
      thioesterase (BTE), an acyl-CoA ligase (FadD), and an acyl-CoA/aldehyde reductase
      (MAACR) were overexpressed in an engineered strain of Escherichia coli. Yields
      were improved by balancing expression levels of each gene, using a fed-batch
      cultivation strategy, and adding a solvent to the culture for extracting the
      product from cells. Using these strategies, a titer of over 1.6 g/L fatty alcohol
      with a yield of over 0.13 g fatty alcohol/g carbon source was achieved. These are
      the highest reported yield of fatty alcohols produced from glucose in E. coli.

PMID- 24141054
TI  - Editorial: scorpion venom and antivenom.

PMID- 24141055
TI  - Ciguatera caused by consumption of humphead wrasse.
AB  - Humphead wrasse (Cheilinus undulatus) is an apex predator from coral reefs of the
      Indo-Pacific region. A food surveillance project using a validated mouse bioassay
      revealed the presence of ciguatoxins in significantly greater amounts in its
      flesh than in groupers and other coral reef fishes commonly available in Hong
      Kong wholesale market. Humphead wrasse has long been known to cause ciguatera,
      but there was a lack of clinical reports. A 45-year-old woman developed ciguatera
      after eating humphead wrasse. She required ICU care and infusions of intravenous
      fluids and dopamine for management of severe hypotension. All 5 published case
      series are also reviewed to characterise the types, severity and chronicity of
      ciguatera symptoms after its consumption. In addition to the gastrointestinal,
      neurological and other features that were typical of ciguatera, some subjects
      developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g.
      mental exhaustion, depression, insomnia and memory loss), other central nervous
      system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia.
      Other subjects still experienced residual symptoms 6 months later; these were
      mainly neurological or neuropsychiatric complaints and skin pruritus. To prevent
      ciguatera, the public should avoid eating humphead wrasse and other large coral
      reef fishes. They should realise that consumption of the high-risk fish may
      result in more severe and chronic illness, including life-threatening
      complications and neuropsychiatric features. 

PMID- 24141056
TI  - Is 1 mm thickness sec. Breslow the correct cut-off for sentinel node biopsy in
      melanoma? Report of six cases of metastasis by thin melanoma.
AB  - AIM: To reassess selection criteria for Sentinel Lymph Node Biopsy (SLNB) in
      patients with thin melanoma (Breslow <= 1 mm). MATERIAL OF STUDY: Between January
      2004 and November 2010 we observed 6 patients with lymph node metastasis from
      early melanoma (Breslow ranging from 0.3 mm to 0.9 mm, not ulcerated tumor,
      mitosis/ mmq < 1). Nobody had received a prior study of sentinel lymph node so
      all patients underwent enlarged lymphadenectomy of concerned lymphatic stations
      and cancer re-staging. RESULTS: The pathological examination of lymph nodes has
      always confirmed metastatic melanoma. The average followup is currently 51,5
      months: 3 of 6 patients presented recurrence that in one case led to death.
      DISCUSSION: In the event of a thickness < 1 mm the probability of finding a
      positive sentinel lymph node is about 7%. Recent data have demonstrated a
      significant survival advantage to early therapeutic lymphadenectomy in melanoma.
      CONCLUSIONS: Our experience, supported by the cases described and the literature,
      leads to propose the technique of SLNB to all patients with melanoma thicker than
      0.5 mm, given the low morbidity and the important prognostic role of the
      procedure, in addition to the possibility of reducing the incidence of lymph node
      metastases.

PMID- 24141058
TI  - Magnetic behaviour of Er1-xZrxFe2 intermetallic compounds.
AB  - In this work, the structural and magnetic properties of Er1-xZrxFe2 (0.1 <= x <=
      0.4) were investigated. These compounds crystallize in the cubic MgCu2 (C15)
      structure, the lattice parameters decreasing with Zr content. Electronic
      structure calculations were performed, showing a good agreement between theory
      and experiment. All of the samples are ferrimagnetically ordered, presenting
      compensation points in the M(T) plots. The compensation point values decrease,
      while the Curie temperatures increase with Zr content. The experimental Fe
      moments at 5 K decrease with Zr content from 1.70 MUB/atom for x = 0.1 to 1.55
      MUB/atom for x = 0.4. A non-collinear orientation of the magnetic moments was
      evidenced in these compounds. The magnetocaloric effect was also studied. A
      modest magnetocaloric effect was found for all of the samples, spreading across a
      wide temperature range. A maximum |DeltaSM| value of 1.19 J kg(-1) K(-1) was
      found for the sample with x = 0.1 for an applied field change of 0-4 T. Large
      RCP(DeltaS) values were obtained for all of the samples, mainly due to the wide
      deltaTFWHM values of the DeltaSM(T) curves. 

PMID- 24141057
TI  - Identification of chemicals inducing cardiomyocyte proliferation in developmental
      stage-specific manner with pluripotent stem cells.
AB  - BACKGROUND: The proliferation of cardiomyocytes is highly restricted after
      postnatal maturation, limiting heart regeneration. Elucidation of the regulatory
      machineries for the proliferation and growth arrest of cardiomyocytes is
      imperative. Chemical biology is efficient to dissect molecular mechanisms of
      various cellular events and often provides therapeutic potentials. We have been
      investigating cardiovascular differentiation with pluripotent stem cells. The
      combination of stem cell and chemical biology can provide novel approaches to
      investigate the molecular mechanisms and manipulation of cardiomyocyte
      proliferation. METHODS AND RESULTS: To identify chemicals that regulate
      cardiomyocyte proliferation, we performed a screening of a defined chemical
      library based on proliferation of mouse pluripotent stem cell-derived
      cardiomyocytes and identified 4 chemical compound groups: inhibitors of glycogen
      synthase kinase-3, p38 mitogen-activated protein kinase, and Ca(2+)/calmodulin
      dependent protein kinase II, and activators of extracellular signal-regulated
      kinase. Several appropriate combinations of chemicals synergistically enhanced
      proliferation of cardiomyocytes derived from both mouse and human pluripotent
      stem cells, notably up to a 14-fold increase in mouse cardiomyocytes. We also
      examined the effects of identified chemicals on cardiomyocytes in various
      developmental stages and species. Whereas extracellular signal-regulated kinase
      activators and Ca(2+)/calmodulin-dependent protein kinase II inhibitors showed
      proliferative effects only on cardiomyocytes in early developmental stages,
      glycogen synthase kinase-3 and p38 mitogen-activated protein kinase inhibitors
      substantially and synergistically induced re-entry and progression of cell cycle
      in neonatal but also as well as adult cardiomyocytes. CONCLUSIONS: Our approach
      successfully uncovered novel molecular targets and mechanisms controlling
      cardiomyocyte proliferation in distinct developmental stages and offered
      pluripotent stem cell-derived cardiomyocytes as a potent tool to explore chemical
      based cardiac regenerative strategies.

PMID- 24141059
TI  - Seroprevalence and risk factors of Chlamydia infection in dogs in Southwestern
      China.
AB  - Chlamydia spp. are obligate intracellular bacteria distributed globally, known to
      cause various forms of diseases in animals and humans. To date, there is limited
      information about the seroprevalence of Chlamydia and the risk factors associated
      with Chlamydia infection in dogs in the world. In the present study, a
      serological survey was undertaken to examine the seroprevalence and risk factors
      associated with dog chlamydiosis in Yunnan Province, southwestern China. A total
      of 591 dogs were sampled, antibodies to Chlamydia were determined by indirect
      hemagglutination assay (IHA). The overall seroprevalence was estimated at 17.6%.
      The risk factors associated with seroprevalence were determined by a multivariate
      logistic regression analysis. Gender and age of dogs were not significant in the
      logistic regression analysis (P>0.05) and left out of the final model. Type and
      geographical origin of dogs were considered as main risk factors associated with
      Chlamydia infection, stray dogs (31.37%) were more than 16 times (OR=16.167, 95%
      CI=6.283-41.599, P<0.01) at risk of acquiring the infection compared to the
      police dogs (7.62%), while pet dogs (14.41%) had a 3 times (OR=2.968, 95%
      CI=1.349-6.529, P=0.007) higher risk. Positive dogs were found in 5 districts of
      Yunnan Province with prevalence ranging from 2.56% to 31.67% except Diqing
      (0/56). Dogs in Kunming (20.21%) had a 9 times higher risk of being seropositive
      compared to dogs in Lijiang (2.56%) (OR=9.057, 95% CI=1.211-67.714, P=0.032),
      although no regional differences were found in other 4 administrative divisions
      compared to Lijiang (P>0.05). Our study revealed a widespread and high prevalence
      of Chlamydia infection in dogs in Yunnan Province, southwestern China, with
      higher exposure risk in stray dogs and distinct geographical distribution. These
      findings suggest the potential importance of dogs in the transmission of zoonotic
      Chlamydia infection, and thus Chlamydia should be taken into consideration in
      diagnosing dog diseases. 

PMID- 24141060
TI  - Establishment of caudal fin cell lines from tropical ornamental fishes Puntius
      fasciatus and Pristolepis fasciata endemic to the Western Ghats of India.

PMID- 24141061
TI  - Changes for the future.

PMID- 24141062
TI  - The chemokine system, and its CCR5 and CXCR4 receptors, as potential targets for
      personalized therapy in cancer.
AB  - Chemokines and their receptors regulate the trafficking of leukocytes in
      hematopoiesis and inflammation, and thus are fundamental to the immune integrity
      of the host. In parallel, members of the chemokine system exert a large variety
      of functions that dictate processes of cancer development and progression.
      Chemokines can act as pro-tumoral or anti-tumoral regulators of malignancy by
      affecting cells of the tumor microenvironment (leukocytes, endothelial cells,
      fibroblasts) and the tumor cells themselves (migration, invasion, proliferation,
      resistance to chemotherapy). Several of the chemokines are generally skewed
      towards the cancer-promoting direction, including primarily the CCR5-CCL5
      (RANTES) and the CXCR4-CXCL12 (SDF-1) axes. This review provides a general view
      of chemokines and chemokine receptors as regulators of malignancy, describing
      their multi-faceted activities in cancer. The tumor-promoting activities of the
      CCR5-CCL5 and CXCR4-CXCL12 pathways are enlightened, emphasizing their potential
      use as targets for personalized therapy. Indeed, novel blockers of chemokines and
      their receptors are constantly emerging, and two chemokine receptor inhibitors
      were recently approved for clinical use: Maraviroc for CCR5 and Plerixafor for
      CXCR4. The review addresses ongoing pre-clinical and clinical trials using these
      modalities and others in cancer. Then, challenges and opportunities of
      personalized therapy directed against chemokines and their receptors in
      malignancy are discussed, demonstrating that such novel personalized cancer
      therapies hold many challenges, but also offer hope for cancer patients. 

PMID- 24141063
TI  - Automated quantification of DNA aneuploidy by image cytometry as an adjunct for
      the cytologic diagnosis of malignant effusion.
AB  - DNA aneuploidy is a cancer biomarker, which may have a potential diagnostic value
      in body effusion specimen. DNA aneuploidy is determined by measuring the DNA
      content of tested cells and comparing them with diploid cells (2c). In order to
      assess the value of automated DNA image cytometry (DNA-ICM) in the cytologic
      diagnosis of effusion, we measured DNA ploidy using an automated DNA-ICM analysis
      system in 126 consecutive effusion specimens and followed the cases for
      histologic diagnosis. Half of each effusion specimen was used to prepare
      cytologic smears for conventional cytologic diagnosis, while the other half was
      used to prepare a monolayer slide stained by Feulgen stain for automated ICM. By
      using Youden index, we found that 4 cells exceeding 2.5c is the optimal cut off
      value for aneuploidy, which has a sensitivity of 88.3% and specificity of 100%
      for diagnosis of malignant effusion. We also found that the DNA aneuploidy
      thresholds used for other types of cytologic specimens cannot be used in the
      diagnosis of effusion specimens. Our study demonstrated that automated DNA image
      cytometry is a simple, practical and cost-effective method for adjunct diagnosis
      of malignant effusion. 

PMID- 24141064
TI  - Development and application of EEAST: a life cycle based model for use of
      harvested rainwater and composting toilets in buildings.
AB  - Harvested rainwater systems and composting toilets are expected to be an
      important part of sustainable solutions in buildings. Yet, to this date, a model
      evaluating their economic and environmental impact has been missing. To address
      this need, a life cycle based model, EEAST was developed. EEAST was designed to
      compare the business as usual (BAU) case of using potable water for toilet
      flushing and irrigation to alternative scenarios of rainwater harvesting and
      composting toilet based technologies. In EEAST, building characteristics,
      occupancy, and precipitation are used to size the harvested rainwater and
      composting toilet systems. Then, life cycle costing and life cycle assessment
      methods are used to estimate cost, energy, and greenhouse gas (GHG) emission
      payback periods (PPs) for five alternative scenarios. The scenarios modeled
      include use of harvested rainwater for toilet flushing, for irrigation, or both;
      and use of composting toilets with or without harvested rainwater use for
      irrigation. A sample simulation using EEAST showed that for the office building
      modeled, the cost PPs were greater than energy PPs which in turn were greater
      than GHG emission PPs. This was primarily due to energy and emission intensive
      nature of the centralized water and wastewater infrastructure. The sample
      simulation also suggested that the composting toilets may have the best
      performance in all criteria. However, EEAST does not explicitly model solids
      management and as such may give composting toilets an unfair advantage compared
      to flush based toilets. EEAST results were found to be very sensitive to cost
      values used in the model. With the availability of EEAST, life cycle cost,
      energy, and GHG emissions can now be performed fairly easily by building
      designers and researchers. Future work is recommended to further improve EEAST
      and evaluate it for different types of buildings and climates so as to better
      understand when composting toilets and harvested rainwater systems outperform the
      BAU case in building design. 

PMID- 24141065
TI  - Multi-scale environmental accounting: methodological lessons from the application
      of NAMEA at sub-national levels.
AB  - Extending the application of integrated environmental and economic accounts from
      the national to the local level of government serves several purposes. They can
      be used not only as an instrument for communicating on the state of the
      environment and reporting the results of policies, but also as an operational
      tool - for setting the objectives and designing policies - if made available to
      the local authorities who have responsibility over the administration of natural
      resources, land use and conservation policies. The aim of the paper is to test
      the feasibility of applying hybrid flow accounts at the intermediate and local
      government levels. As an illustration, NAMEA for air emissions and wastes is
      applied to a Region, a Province and a Municipality, thus covering the three
      nested levels of local government in Italy. The study identifies the main issues
      raised by multi-scale environmental accounting and provides an applied discussion
      of feasible solutions. 

PMID- 24141066
TI  - Optimization by Response Surface Methodology of the adsorption of Coomassie Blue
      dye on natural and acid-treated clays.
AB  - The effect of acid treatment on natural agalmatolite (AN) and natural kaolinite
      (KN) was investigated, together with the influence of those modifications on the
      removal of Coomassie Blue (CB) dye. The process was optimized using the Response
      Surface Methodology (RSM) developed by the application of the quadratic model
      associated with the Central Composite Design. Adsorption was promoted by initial
      CB concentration of 25 mg L(-1), pH 2 and adsorbent mass of 0.1 g. The adsorption
      kinetics study carried out in optimized conditions established that the
      equilibrium times were 1 h for AN and AA (treated agalmatolite), 4 h for KN and 2
      h for KA (treated kaolinite). The kinetics data for AN, KN and KA were best
      fitted to the pseudo second order model, whilst for AA, the result pointed to the
      pseudo first order model. In the isotherm of adsorption the maximum quantities
      were obtained with reference to 11.29 mg g(-1), 9.84 mg g(-1), 22.89 mg g(-1) and
      30.08 mg g(-1) for the samples AN, AA, KN and KA respectively. The data fitting
      showed that the Sips model was the most satisfactory for all the adsorbents. The
      calculated thermodynamic parameters showed that the process was spontaneous in
      all the adsorbents, endothermic for the KN and KA samples, exothermic for AN and
      AA, involved the disorganization of the adsorption system for the KN and KA and
      its organization for the AN and AA samples. The results showed that the KN and KA
      samples were more appropriate for use as adsorbents. 

PMID- 24141067
TI  - Synthesis of chitosan based nanoparticles and their in vitro evaluation against
      phytopathogenic fungi.
AB  - The main aim of present study was to prepare chitosan, chitosan-saponin and Cu
      chitosan nanoparticles to evaluate their in vitro antifungal activities. Various
      nanoparticles were prepared using ionic gelation method by interaction of
      chitosan, sodium tripolyphosphate, saponin and Cu ions. Their particle size,
      polydispersity index, zeta potential and structures were confirmed by DLS, FTIR,
      TEM and SEM. The antifungal properties of nanoparticles against phytopathogenic
      fungi namely Alternaria alternata, Macrophomina phaseolina and Rhizoctonia solani
      were investigated at various concentrations ranging from 0.001 to 0.1%. Among the
      various formulations of nanoparticles, Cu-chitosan nanoparticles were found most
      effective at 0.1% concentration and showed 89.5, 63.0 and 60.1% growth inhibition
      of A. alternata, M. phaseolina and R. solani, respectively in in vitro model. At
      the same concentration, Cu-chitosan nanoparticles also showed maximum of 87.4%
      inhibition rate of spore germination of A. alternata. Chitosan nanoparticles
      showed the maximum growth inhibitory effects (87.6%) on in vitro mycelial growth
      of M. phaseolina at 0.1% concentration. From our study it is evident that
      chitosan based nanoparticles particularly chitosan and Cu-chitosan nanoparticles
      have tremendous potential for further field screening towards crop protection. 

PMID- 24141068
TI  - Synthesis and characterization of polypyrrole grafted cellulose for humidity
      sensing.
AB  - The present communication reports the synthesis of polypyrrole-grafted-cellulose
      (PPy-g-Cellu) copolymer by a chemical method at ambient condition. The
      representative samples of PPy-g-Cellu were characterized using infra red
      spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope
      (SEM), UV-vis spectroscopy (UV-vis) and themogravimetry (TG) techniques. The
      prepared copolymer was crystalline in nature with improved thermal stability.
      Further, electrical properties reveals the formation of polypyrole grafted
      cellulose copolymer with 10(7) fold improved electrical conductivity and 10(2)
      folds hydrophillcity than cellulose and polypyrrole, respectively. The electrical
      resistance of a PPy-g-Cellu film casted on a glass substrate was measured as
      function of relative humidity in the range of 5-95% to explore its use for
      humidity sensing purposes. Finally, PPy-g-Cellu offers a promising perspective as
      a humidity sensing material with response time 25 s, recovery time 20 s and
      stability for 40 days.

PMID- 24141069
TI  - Carboxymethyl inulin: a novel flocculant for wastewater treatment.
AB  - Carboxymethyl inulin (CMI) has been synthesized by incorporation of carboxymethyl
      groups in the inulin framework; by reacting inulin with sodium salt of monochloro
      acetic acid (SMCA) in presence of sodium hydroxide. The resulting
      carboxymethylated product, with different degrees of substitution, has been
      confirmed through various physicochemical characterization techniques, such as
      intrinsic viscosity measurement, elemental analysis (C, H, N and O), FTIR
      spectroscopy, thermogravimetric analysis (TGA) and scanning electron microscopy
      (SEM) studies. Flocculation efficacy of various grades of CMI, have been studied
      in kaolin suspension and then in municipal wastewater, in relation to inulin
      (parent polysaccharide). This has been done utilizing jar-test procedure towards
      possible application as a flocculant for waste water treatment. 

PMID- 24141070
TI  - Structural changes in R-phycoerythrin upon CdS quantum dot synthesis in tunnel
      cavities of protein molecules.
AB  - Structural changes in R-phycoerythrin used as a matrix for the synthesis of CdS
      quantum dots have been analyzed by circular dichroism spectrometry. In deionized
      water, quantum dot synthesis in the tunnel cavity of the R-phycoerythrin molecule
      proved to be accompanied by uncoiling of alpha-helices and changes in the
      conformation of its chromophore groups, with consequent decay of protein
      fluorescence. Since R-phycoerythrin fluorescence is important for practical
      applications, conditions for quantum dot synthesis have been optimized by
      replacing deionized water with 0.01 M MES buffer, pH 5.7. Under such conditions,
      the size of the CdS quantum dots (determined from atomic force microscopy images)
      remains the same as in deionized water, but quantum dots cause only minor
      structural changes in protein molecules, as follows from circular dichroism and
      absorption spectra. The thermostability of R-phycoerythrin is enhanced, as
      indicated by an increase in the experimental activation energy for denaturation
      (from 140.8 to 149.9 kJ/mol) and the intensity of R-phycoerythrin fluorescence is
      also enhanced approximately twofold.

PMID- 24141071
TI  - Preparation of TEMPO-oxidized cellulose/amino acid/nanosilver biocomposite film
      and its antibacterial activity.
AB  - Novel biocomposite films were prepared by employing amino acid phenylalanine
      (Phe) or tryptophan (Try) functionalized TEMPO-oxidized cellulose (TOC) with
      silver nanoparticles (AgNPs) produced in situ by reduction with silver nitrate
      and sodium borohydride via homogeneous and heterogeneous approaches. The as
      prepared biocomposite films, i.e. TOC-Phe-AgNPs and TOC-Try-AgNPs, were
      characterized by digital photographs, FTIR, Elemental Analysis, SEM, and TEM and
      the results confirmed the formation of the desired films. The in vitro
      antibacterial activity of two resulting composite film of TOC-Phe-AgNPs and TOC
      Try-AgNPs was evaluated against Staphylococcus aureus and Escherichia coli
      bacteria by agar diffusion test. 

PMID- 24141072
TI  - Cloning and heterologous expression of a thermostable pectate lyase from
      Penicillium occitanis in Escherichia coli.
AB  - The entire pectate lyase cDNA (Pel1) of Penicillium occitanis was cloned from a
      cDNA bank and sequenced. The ORF exhibited a great homology to Penicillium
      marneffei and conservation of all features of fungal pectate lyases such as the
      barrel structure with "eight right-handed parallel beta-helix" architecture. The
      structure modeling also showed the interesting resemblance with thermostable
      pectate lyases since several specific residues were also shared by Pel1 and these
      thermostable enzymes. Having shown that the enzyme retains its activity after
      endoH-mediated deglycosylation, we investigated its expression in Escherichia
      coli BL21 using the pET28-a vector. This expression was shown to be optimum when
      cells were induced at room temperature in 2YT medium rather than at 37  degrees C
      and LB medium. In such conditions, the recombinant protein was apparently
      produced more in soluble form than as inclusion bodies. The effect of NaCl
      concentration was investigated during the binding and elution steps of
      recombinant His-tagged enzyme on MagneHis Ni-particles. The purified enzyme was
      shown to retain its thermo-activity as well as a great tolerance to high
      concentration of NaCl and imidazole.

PMID- 24141073
TI  - Flor yeasts of Saccharomyces cerevisiae--their ecology, genetics and metabolism.
AB  - The aging of certain white wines is dependent on the presence of yeast strains
      that develop a biofilm on the wine surface after the alcoholic fermentation.
      These strains belong to the genus Saccharomyces and are called flor yeasts. These
      strains possess distinctive characteristics compared with Saccharomyces
      cerevisiae fermenting strain. The most important one is their capacity to form a
      biofilm on the air-liquid interface of the wine. The major gene involved in this
      phenotype is FLO11, however other genes are also involved in velum formation by
      these yeast and will be detailed. Other striking features presented in this
      review are their aneuploidy, and their mitochondrial DNA polymorphism which seems
      to reflect adaptive evolution of the yeast to a stressful environment where
      acetaldehyde and ethanol are present at elevated concentration. The biofilm
      assures access to oxygen and therefore permits continued growth on non
      fermentable ethanol. This specific metabolism explains the peculiar organoleptic
      profile of these wines, especially their content in acetaldehyde and sotolon.
      This review deals with these different specificities of flor yeasts and will also
      underline the existing gaps regarding these astonishing yeasts. 

PMID- 24141074
TI  - Sex differences in sleep-dependent perceptual learning.
AB  - Sex differences in learning and memory suggest differences between men and women
      in mechanisms of neural plasticity. Such differences have been reported in a
      variety of explicit memory tasks, but implicit memory has not been studied in
      this context. We investigated differences between men and women in offline
      consolidation of perceptual learning (PL) of motion direction discrimination.
      Initially, discrimination thresholds were measured for two opposite directions of
      motion, followed by approximately 40 minutes of training on one of the
      directions. During a post-training consolidation period, subjects either took a
      nap or remained awake. Thresholds were then reassessed for both directions of
      motion. We found that rapid eye movement (REM) sleep facilitates consolidation of
      PL but that the pattern of specificity in the REM condition differed between men
      and women. PL for men whose naps contained REM sleep was highly specific to the
      trained direction of motion, whereas REM sleep in women resulted in generalized
      learning to the untrained direction as well as to a novel direction that was not
      previously tested. Moreover, for subjects in the REM condition, men exhibited
      greater PL than women for the trained direction. Our findings provide the first
      evidence of sex differences in the magnitude and specificity of PL and in the
      role of REM sleep in implicit learning. Our results have important implications
      for optimization of educational and training strategies designed for males and
      females.

PMID- 24141075
TI  - Crude and purified proteasome activity assays are affected by type of microplate.
AB  - Measurement of proteasome activity is fast becoming a commonly used assay in many
      laboratories. The most common method to measure proteasome activity involves
      measuring the release of fluorescent tags from peptide substrates in black
      microplates. Comparisons of black plates used for measuring fluorescence with
      different properties show that the microplate properties significantly affect the
      measured activities of the proteasome. The microplate that gave the highest
      reading of trypsin-like activity of the purified 20S proteasome gave the lowest
      reading of chymotrypsin-like activity of the 20S proteasome. Plates with medium
      binding surfaces from two different companies showed an approximately 2-fold
      difference in caspase-like activity for purified 20S proteasomes. Even standard
      curves generated using free 7-amino-4-methylcoumarin (AMC) were affected by the
      microplate used. As such, significantly different proteasome activities, as
      measured in nmol AMC released/mg/min, were obtained for purified 20S proteasomes
      as well as crude heart and liver samples when using different microplates. The
      naturally occurring molecule betulinic acid activated the chymotrypsin-like
      proteasome activity in three different plates but did not affect the proteasome
      activity in the nonbinding surface microplate. These findings suggest that the
      type of proteasome activity being measured and sample type are important when
      selecting a microplate. 

PMID- 24141076
TI  - Microbial fluorescence sensing for human neurotensin receptor type 1 using Galpha
      engineered yeast cells.
AB  - Neurotensin receptor type-1 (NTSR1) is a member of the G-protein-coupled receptor
      (GPCR) family. The natural ligand of NTSR1 is neurotensin (NT), a neuromodulator
      of the central nervous system. Because NT is also involved in many oncogenic
      actions, the signaling mediator NTSR1 is a significant molecular target in
      medicinal and therapeutic fields. In the current study, we constructed a
      fluorescence-based microbial yeast biosensor that can monitor the activation of
      human NTSR1 signaling responding to its agonist. To increase the sensitivity of
      the biosensor, a yeast strain with the green fluorescent protein (GFP) reporter
      gene was genetically engineered to enhance binding with human NTSR1 expressed on
      the membrane. Following previous reports, the 5 carboxy-terminal amino acid
      residues of the guanine nucleotide binding protein alpha-subunit (Galpha) in
      yeast Gpa1p were substituted with the equivalent human Galpha(q) sequences
      (Gpa1/Galpha(q) transplant). After optimizing the assay conditions, the Galpha
      engineered yeast demonstrated significantly improved sensing for NTSR1 signaling.
      Because detection using a GFP fluorescence reporter considerably simplifies the
      measurement procedure, this microbial fluorescence sensor holds promise for use
      in the diagnosis of NTSR1-associated diseases and the development of agonists.

PMID- 24141077
TI  - Refining membrane penetration by a combination of steady-state and time-resolved
      depth-dependent fluorescence quenching.
AB  - Accurate determination of the depth of membrane penetration of a fluorescent
      probe, attached to a lipid, protein, or other macromolecule of interest, using
      depth-dependent quenching methodology is complicated by thermal motion in the
      lipid bilayer. Here, we suggest that a combination of steady-state and time
      resolved measurements can be used to generate a static quenching profile that
      reduces the contribution from transverse diffusion occurring during the excited
      state lifetime. This procedure results in narrower quenching profiles, compared
      with those obtained by traditional measurements, and thus improves precision in
      determination of the underlying depth distribution of the probe. 

PMID- 24141078
TI  - Fabrication of a highly sensitive disposable immunosensor based on indium tin
      oxide substrates for cancer biomarker detection.
AB  - Anti-HER-3 antibody was used for the first time in a disposable immunosensor
      based on indium tin oxide (ITO) substrate for HER-3 quantification. Anti-HER-3
      was immobilized onto ITO substrate by 3-aminopropyl)triethoxysilane (APTES) and
      glutaraldehyde. This highly sensitive immunosensor was capable of detecting
      concentrations of HER-3 down to the femtogram/ml level by investigating changes
      in the charge transfer resistance (R(ct)) using electrochemical impedance
      spectroscopy (EIS). Construction of ITO layers was carefully investigated using a
      broad range of techniques such as voltammetry, EIS, atomic force microscopy
      (AFM), and scanning electron microscopy (SEM). Meanwhile, in an immunosensor
      system, the "single frequency impedance" technique was first used for
      characterization of interaction between HER-3 and anti-HER-3. Eventually, the
      proposed ITO-based immunosensor was applied to artificial serum samples spiked
      with HER-3.

PMID- 24141079
TI  - Conformational preference of glycinamide in solution: an answer derived from
      combined experimental and computational studies.
AB  - Conformational problems are often subtle but very important in controlling many
      intricate features in chemistry and biochemistry. We have performed the
      conformational analysis of glycinamide using NMR experiments and computational
      studies. (1)H NMR experiments suggest the prevalence of intramolecular hydrogen
      bonded conformation of glycinamide (2B) in acetonitrile, whereas, non
      intramolecular hydrogen bonded conformation 2A is favoured in dimethylsulfoxide.
      The NOESY experiments carried out for glycinamide in DMSO-d6, showed stronger NOE
      interaction of the NHa-atom of amide group with CH2 than that of NHb-atom
      confirming the presence of conformer 2A. DFT calculations performed with explicit
      DMSO molecules also suggested a clear preference for the conformer 2A. The
      molecular dynamics simulations performed with the explicit DMSO molecules also
      showed that the intermolecular hydrogen bonding exists between the solvent and
      solute molecules to stabilize the conformer 2A. The present study sheds light on
      the debate of conformational preference of neutral glycinamide in the present
      literature. 

PMID- 24141080
TI  - Metal-coated semiconductor nanostructures and simulation of photon extraction and
      coupling to optical fibers for a solid-state single-photon source.
AB  - We have realized metal-coated semiconductor nanostructures for a stable and
      efficient single-photon source (SPS) and demonstrated improved single-photon
      extraction efficiency by the selection of metals and nanostructures. We
      demonstrate with finite-difference time-domain (FDTD) simulations that
      inclination of a pillar sidewall, which changes the structure to a nanocone, is
      effective in improving the photon extraction efficiency. We demonstrate how such
      nanocone structures with inclined sidewalls are fabricated with reactive ion
      etching. With the optimized design, a photon extraction efficiency to outer
      airside as high as ~97% generated from a quantum dot in a nanocone structure is
      simulated, which is the important step in realizing SPS on-demand operations. We
      have also examined the direct contact of such a metal-embedded nanocone structure
      with a single-mode fiber facet as a simple and practical method for preparing
      fiber-coupled SPS and demonstrated practical coupling efficiencies of ~16% with
      FDTD simulation.

PMID- 24141081
TI  - Total scattering analysis of cation coordination and vacancy pair distribution in
      Yb substituted delta-Bi2O3.
AB  - Reverse Monte Carlo (RMC) modelling of neutron total scattering data, combined
      with conventional Rietveld analysis of x-ray and neutron data, has been used to
      describe the cation coordination environments and vacancy pair distribution in
      the oxide ion conducting electrolyte Bi3YbO6. The thermal variation of the cubic
      fluorite unit cell volume, monitored by variable temperature x-ray and neutron
      experiments, reveals significant curvature, which is explained by changes in the
      oxide ion distribution. There is a significant increase in tetrahedral oxide ion
      vacancy concentration relative to delta-Bi2O3, due to the creation of Frenkel
      defects associated with the Yb(3+) cation. The tetrahedral oxide ion vacancy
      concentration increases from room temperature to 800  degrees C, but little
      change is observed in the vacancy pair distribution with temperature. The vacancy
      pair distributions at both temperatures are consistent with a favouring of [100]
      vacancy pairs.

PMID- 24141082
TI  - ABCA7 expression is associated with Alzheimer's disease polymorphism and disease
      status.
AB  - Genome-wide association studies (GWAS) have implicated a series of single
      nucleotide polymorphisms (SNPs) in Alzheimer's disease (AD) risk. Elucidating the
      function of these SNPs is critical to identify the underlying pathways and,
      potentially, novel therapeutic agents. SNPs within the gene ATP binding cassette
      A7 (ABCA7) reached significance in these studies, warranting investigation into
      their actions. Here, we analyzed ABCA7 expression in a set of human brain samples
      as a function of AD-associated SNPs and AD status. We report that the rs3764650T
      allele that decreases AD risk is associated with increased ABCA7 expression.
      However, ABCA7 expression is increased in AD individuals. We interpret our
      findings as suggesting a model wherein increased ABCA7 expression reduces AD risk
      and that the increased ABCA7 observed in AD reflects an inadequate compensatory
      change. 

PMID- 24141083
TI  - ERPs show that classroom-instructed late second language learners rely on the
      same prosodic cues in syntactic parsing as native speakers.
AB  - The loss of brain plasticity after a 'critical period' in childhood has often
      been argued to prevent late language learners from using the same neurocognitive
      mechanisms as native speakers and, therefore, from attaining a high level of
      second language (L2) proficiency [7,11]. However, more recent behavioral and
      electrophysiological research has challenged this 'Critical Period Hypothesis',
      demonstrating that even late L2 learners can display native-like performance and
      brain activation patterns [17], especially after longer periods of immersion in
      an L2 environment. Here we use event-related potentials (ERPs) to show that
      native-like processing can also be observed in the largely under-researched
      domain of speech prosody - even when L2 learners are exposed to their second
      language almost exclusively in a classroom setting. Participants listened to
      spoken sentences whose prosodic boundaries would either cooperate or conflict
      with the syntactic structure. Previous work had shown that this paradigm is
      difficult for elderly native speakers, however, German L2 learners of English
      showed very similar ERP components for on-line prosodic phrasing as well as for
      prosody-syntax mismatches (garden path effects) as the control group of native
      speakers. These data suggest that L2 immersion is not always necessary to master
      complex L2 speech processing in a native-like way.

PMID- 24141084
TI  - Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix
      metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with
      clozapine.
AB  - Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of
      neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF
      levels in patients with schizophrenia have been widely reported in the
      literature. However, it is still controversial whether peripheral levels of BDNF
      are altered in patients with schizophrenia. The peripheral BDNF levels previously
      reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF)
      as it was unable to specifically measure mature BDNF due to limited BDNF antibody
      specificity. In this study, we examined whether peripheral levels of mature BDNF
      were altered in patients with treatment-resistant schizophrenia. Matrix
      metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in
      the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment
      resistant schizophrenia treated with clozapine and 22 age- and sex-matched
      healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were
      measured using ELISA kits. No significant difference was observed for mature BDNF
      however, MMP-9 was significantly increased in patients with schizophrenia. The
      significant correlation was observed between mature BDNF and MMP-9 plasma levels.
      Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables.
      Our results do not support the view that peripheral BDNF levels are associated
      with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia
      and serve as a biomarker for schizophrenia. 

PMID- 24141085
TI  - Waddlia chondrophila: from biology to pathogenicity.
AB  - Waddlia chondrophila is an emerging pathogen causing miscarriages in humans and
      abortions in ruminants. The full genome of this Chlamydia-related bacterium has
      been recently completed, providing new insights into its biology and evolution.
      Moreover, new cell biology approaches and the use of novel inhibitors have
      allowed detailed investigations of its interaction with host cells. 

PMID- 24141086
TI  - The Brucella pathogens are polarized bacteria.
AB  - Brucella pathogens are responsible for brucellosis, a worldwide zoonosis. They
      are facultative intracellular pathogens characterized by their asymmetric
      division and their unipolar growth. This growth modality generates poles with
      specialized functions (through polar recruitment of polar adhesins or of cell
      cycle regulators) and progeny cells with potentially different fates. 

PMID- 24141087
TI  - Ehrlichia moonlighting effectors and interkingdom interactions with the
      mononuclear phagocyte.
AB  - Ehrlichia chaffeensis is an obligately intracellular gram negative bacterium with
      a small genome that thrives in mammalian mononuclear phagocytes by exploiting
      eukaryotic processes. Herein, we discuss the latest findings on moonlighting
      tandem repeat protein effectors and their secretion mechanisms, and novel
      molecular interkingdom interactions that provide insight into the intracellular
      pathobiology of ehrlichiae. 

PMID- 24141089
TI  - F(ab')2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes
      HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket.
AB  - Using a recombinant protein N46FdFc that mimics the HIV-1 gp41 N-helix trimer to
      immunize mice, we identified the first IgM monoclonal antibody 18D3 that
      specifically bound to the conserved gp41 pocket. Its F(ab')2 fragment potently
      inhibited HIV-1 Env-mediated cell-cell fusion and neutralized infection by
      laboratory-adapted and primary HIV-1 isolates with different subtypes and
      tropism, including the T20-resistant variants. This F(ab')2 fragment can be used
      to develop a bispecific broad neutralizing monoclonal antibody or HIV-1
      inactivator as a novel immunotherapeutic for treatment and prevention of HIV-1
      infection. 

PMID- 24141088
TI  - A path forward for the chlamydial virulence factor CPAF.
AB  - CPAF is a conserved and secreted protease from obligate intracellular bacteria of
      the order Chlamydiales. Recently, it was demonstrated that most of its host
      targets are an artifact of inaccurate methods. This review aims to summarize key
      features of CPAF and propose new approaches for evaluating its role in chlamydial
      pathogenesis. 

PMID- 24141090
TI  - Pathogenesis and cell corruption by intracellular bacteria.

PMID- 24141091
TI  - Breaking in and grabbing a meal: Anaplasma phagocytophilum cellular invasion,
      nutrient acquisition, and promising tools for their study.
AB  - Anaplasma phagocytophilum invades neutrophils to cause the emerging infection,
      human granulocytic anaplasmosis. Here, we provide a focused review of the A.
      phagocytophilum invasin-host cell receptor interactions that promote bacterial
      entry and the degradative and membrane traffic pathways that the organism
      exploits to route nutrients to the organelle in which it resides. Because its
      obligatory intracellular nature hinders knock out-complementation approaches, we
      also discuss the current methods used to study A. phagocytophilum gene function
      and the potential benefit of applying novel tools that have advanced studies of
      other obligate intracellular bacterial pathogens. 

PMID- 24141092
TI  - Male survivors of allogeneic hematopoietic stem cell transplantation have a long
      term persisting risk of cardiovascular events.
AB  - Long-term survivors of allogeneic stem cell transplantation (SCT) have increased
      risk of cardiovascular disease. We retrospectively studied cardiovascular risk
      factors (CVRFs) in 109 SCT survivors (62 males, 47 females; median age 34 years)
      five years or more after bone marrow (15) or T cell-depleted peripheral blood
      (94) SCT for CML (56), acute leukemia (29), MDS (13), and others (11). One death
      and two cardiovascular events were reported. At five and ten years after SCT,
      respectively, 44% and 52% had abnormal lipid profiles; 23% of 5-year survivors
      met the Adult Treatment Panel III threshold for dyslipidemia treatment, which is
      substantially higher than the age-matched general population. There were
      significant increases in prevalence of hypertension (p < 0.001), diabetes (p =
      0.018), and body mass index (p = 0.044) after SCT compared with baseline. The
      Framingham general cardiovascular risk score (FGCRS) in males at five years after
      SCT projected a doubling (median 10.4% vs. 5.4%) in the 10-year risk of
      cardiovascular events. Females received HRT after SCT, and none had increased
      FGCRS. Chronic GVHD and C-reactive protein were not associated with CVRF at any
      time. All CVRFs stabilized between five and ten years after SCT. Thus, SCT
      survivors have sustained elevations in CVRFs. Males have a significantly
      increased risk of cardiovascular events in their second and third decade after
      SCT.

PMID- 24141093
TI  - 59Fe-distribution in conditional ferritin-H-deleted mice.
AB  - The objective was to explore how ferritin-H deletion influences (59)Fe
      distribution and excretion-kinetics in mice. Kinetics of (59)Fe-release from
      organs, whole-body excretion, and distribution-kinetics of intravenously injected
      (59)Fe trace amounts were compared in iron-deficient and iron-replete mice with
      (Fth(Delta/Delta)) and without (Fth(lox/lox)) conditional Mx-Cre-induced ferritin
      H deletion. (59)Fe was released from spleen and liver beginning on day 2 and day
      5 after ferritin-H deletion, respectively, but was not excreted from the body.
      Plasma-(59)Fe was cleared significantly faster in iron-deficient Fth(Delta/Delta)
      mice than in iron-adequate Fth(lox/lox)-controls. (59)Fe-distribution showed a
      transient peak (e.g., in heart, kidney, muscle) in Fth(lox/lox) control mice, but
      not in ferritin-H-deleted Fth(Delta/Delta) mice 24 hours after (59)Fe injection.
      (59)Fe uptake into the liver and spleen was significantly lower in iron-deficient
      Fth(Delta/Delta) than in Fth(lox/lox) mice 24 hours and 7 days after injection,
      respectively, and rapidly appeared in circulating erythrocytes instead. The rate
      of (59)Fe release after ferritin-H deletion supports earlier data on ferritin
      turnover in mammals; released (59)Fe is not excreted from the body. Instead,
      (59)Fe is channeled into erythropoiesis and circulating erythrocytes
      significantly more extensively and faster. Along with a lack of transient interim
      (59)Fe storage (e.g., in the heart and kidney), this finding is evidence for
      ferritin-related iron storage-capacity affecting rate and extent of iron
      utilization.

PMID- 24141094
TI  - The P body protein LSm1 contributes to stimulation of hepatitis C virus
      translation, but not replication, by microRNA-122.
AB  - The P body protein LSm1 stimulates translation and replication of hepatitis C
      virus (HCV). As the liver-specific microRNA-122 (miR-122) is required for HCV
      replication and is associated with P bodies, we investigated whether regulation
      of HCV by LSm1 involves miR-122. Here, we demonstrate that LSm1 contributes to
      activation of HCV internal ribosome entry site (IRES)-driven translation by miR
      122. This role for LSm1 is specialized for miR-122 translation activation, as
      LSm1 depletion does not affect the repressive function of miR-122 at 3'
      untranslated region (UTR) sites, or miR-122-mediated cleavage at a perfectly
      complementary site. We find that LSm1 does not influence recruitment of the
      microRNA (miRNA)-induced silencing complex to the HCV 5'UTR, implying that it
      regulates miR-122 function subsequent to target binding. In contrast to the
      interplay between miR-122 and LSm1 in translation, we find that LSm1 is not
      required for miR-122 to stimulate HCV replication, suggesting that miR-122
      regulation of HCV translation and replication have different requirements. For
      the first time, we have identified a protein factor that specifically contributes
      to activation of HCV IRES-driven translation by miR-122, but not to other
      activities of the miRNA. Our results enhance understanding of the mechanisms by
      which miR-122 and LSm1 regulate HCV. 

PMID- 24141095
TI  - Non-biased and efficient global amplification of a single-cell cDNA library.
AB  - Analysis of single-cell gene expression promises a more precise understanding of
      molecular mechanisms of a living system. Most techniques only allow studies of
      the expressions for limited numbers of gene species. When amplification of cDNA
      was carried out for analysing more genes, amplification biases were frequently
      reported. A non-biased and efficient global-amplification method, which uses a
      single-cell cDNA library immobilized on beads, was developed for analysing entire
      gene expressions for single cells. Every step in this analysis from reverse
      transcription to cDNA amplification was optimized. By removing degrading excess
      primers, the bias due to the digestion of cDNA was prevented. Since the residual
      reagents, which affect the efficiency of each subsequent reaction, could be
      removed by washing beads, the conditions for uniform and maximized amplification
      of cDNAs were achieved. The differences in the amplification rates for randomly
      selected eight genes were within 1.5-folds, which could be negligible for most of
      the applications of single-cell analysis. The global amplification gives a large
      amount of amplified cDNA (>100 MUg) from a single cell (2-pg mRNA), and that
      amount is enough for downstream analysis. The proposed global-amplification
      method was used to analyse transcript ratios of multiple cDNA targets (from
      several copies to several thousand copies) quantitatively. 

PMID- 24141097
TI  - Incidence and predictors of end-stage renal disease in outpatients with systolic
      heart failure.
AB  - BACKGROUND: Renal dysfunction is an important prognostic factor in heart failure
      (HF), but whether this dysfunction progresses to end-stage renal disease (ESRD)
      is unknown. Therefore, we examined incidence and predictors of ESRD in
      outpatients with HF. METHODS AND RESULTS: Patients with systolic HF were
      identified in The Danish Heart Failure database and new-onset ESRD from the
      Danish Registry on Dialysis. Renal function was estimated by The Chronic Kidney
      Disease Epidemiology Collaboration equation and patients grouped by estimated
      glomerular filtration rate (eGFR)-group I: >=60 mL/min per 1.73 m(2), group II:
      30 to 59 mL/min per 1.73 m(2), group III: 15 to 29 mL/min per 1.73 m(2), group
      IV: <15 mL/min per 1.73 m(2). Cox hazard models for time to ESRD, to death, and
      the composite end point of ESRD or death were constructed and predictors of ESRD
      identified. A total of 8204 patients were included in the analyses. Median age
      was 70 years (Q, 61-77), 28% were women, median left ventricular ejection
      fraction was 30% (Q, 24-40), and median eGFR was 68 (Q, 51-85) mL/min per 1.73
      m(2). Forty-one patients developed ESRD (1.3/1000 patient-years). Baseline eGFR
      group II (P<0.001), eGFR group III (P<0.001), eGFR group IV (P<0.001),
      uncontrolled hypertension (P=0.049), need of diuretics, and age <60 years
      (P=0.016) were associated with time to ESRD. CONCLUSIONS: ESRD is rare in
      outpatients with systolic HF and is mainly observed in patients with an eGFR <30
      mL/min per 1.73 m(2). A low eGFR, age <60 years, need of diuretics, and
      uncontrolled hypertension identify patients with an increased risk for ESRD.

PMID- 24141098
TI  - Yoctomole detection of proteins using solid phase binding-induced DNA assembly.
AB  - A binding-induced DNA assembly (BINDA) strategy is able to covert target-binding
      to amplifiable DNA assembly, thereby extending advances in DNA amplification to
      the detection of other non-amplifiable molecules. We describe here the concept of
      solid phase BINDA and demonstrate an approach of detecting proteins using
      affinity capture of the specific proteins on magnetic beads followed by BINDA.
      The antibody-coated magnetic beads are first introduced to capture target
      proteins from sample solutions. The unbound components are removed by washing.
      Two affinity probes, each conjugated to a DNA motif, are utilized to bind to the
      captured protein molecules. The binding of the two probes to the same target
      molecule induces assembly of the two DNA motifs that are conjugated to affinity
      ligands. Enzymatic ligation of the two DNA motifs generates a new DNA sequence
      that is then measured with real-time PCR. The highly sensitive real-time PCR
      detection of the DNA assembly provides an indirect detection of the target
      proteins that is responsible for the binding-induced DNA assembly. The
      incorporation of solid phase affinity capture effectively reduces the potential
      interferences from complex matrix and further improves the sensitivity of protein
      detection by pre-concentration. An application of the technique to the
      determination of prostate specific antigen in dilute serum shows a detection
      limit of 200 yoctomole (2*10(-22) mol) from a 20-MUL sample. The concentration
      detection limit (10 attomolar) is 10-fold lower than using the homogeneous BINDA.
      Substantial reduction of background is a main reason for the improvement in
      detection limits observed with the BINDA assays. Solid phase BINDA complements to
      homogeneous BINDA for accomplishing ultrasensitive protein detection.

PMID- 24141099
TI  - Variation in Latent Classes of Adult Attention-Deficit Hyperactivity Disorder by
      Sex and Environmental Adversity.
AB  - OBJECTIVE: The findings of genetic, imaging and neuropsychological studies of
      attention-deficit hyperactivity disorder (ADHD) are mixed. To understand why this
      might be the case we use both dimensional and categorical symptom measurement to
      provide alternate and detailed perspectives of symptom expression. METHOD:
      Interviewers collected ADHD, conduct problems (CP) and sociodemographic data from
      3793 twins and their siblings aged 22 to 49 (M = 32.6). We estimate linear
      weighting of symptoms across ADHD and CP items. Latent class analyses and
      regression describe associations between measured variables, environmental risk
      factors and subsequent disadvantage. Additionally, the clinical relevance of each
      class was estimated. RESULTS: Five classes were found for women and men; few
      symptoms, hyperactive-impulsive, CP, inattentive, combined symptoms with CP.
      Women within the inattentive class reported more symptoms and reduced emotional
      health when compared to men and to women within other latent classes. Women and
      men with combined ADHD symptoms reported comorbid conduct problems but those with
      either inattention or hyperactivity-impulsivity only did not. CONCLUSION: The
      dual perspective of dimensional and categorical measurement of ADHD provides
      important detail about symptom variation across sex and with environmental
      covariates.

PMID- 24141100
TI  - The Impact of Coexisting Emotional and Conduct Problems on Family Functioning and
      Quality of Life Among Adolescents With ADHD.
AB  - OBJECTIVE: The aim of this study was to assess the impact of self-reported
      emotional and conduct problems on family functioning and quality of life (QoL)
      among adolescents with ADHD. METHOD: The ADHD group (N = 194) was divided into
      the following groups: without additional emotional or conduct problems, with
      emotional problems, with conduct problems, and with both problem types. The cross
      sectional study included parent and adolescent reports. RESULTS: Adolescents with
      ADHD and both problem types reported significantly lower QoL and family
      functioning than all other ADHD groups. Parents reported better QoL for the ADHD
      group without additional problems, but similar family functioning for all groups.
      CONCLUSION: A higher level of coexisting psychiatric problems had a significant
      impact on adolescents' reports of family functioning and QoL. However, coexisting
      problems showed no association with parent reports of family functioning.
      Adolescents with ADHD might add important information in clinical assessment.

PMID- 24141101
TI  - Attention Problems and Academic Achievement: Do Persistent and Earlier-Emerging
      Problems Have More Adverse Long-Term Effects?
AB  - OBJECTIVE: This study examined whether the negative association between
      children's attention difficulties and their academic functioning is largely
      confined to children whose attention problems persist across early grades and
      whether it depends on when attention problems emerge in children's schooling.
      METHOD: Children from the normative sample of the Fast Track study were
      classified into four attention problem groups based on the presence versus
      absence of attention problems in first and second grade. RESULTS: Those with
      attention problems in both grades showed a decline in reading and math
      achievement during the K-5 interval relative to children with attention problems
      in first grade only. Both groups of inattentive first graders also performed
      worse than comparison children. In contrast, children whose attention problems
      emerged in second grade did not differ from comparison children on any
      achievement outcome performed significantly better than inattentive first
      graders. CONCLUSION: The implications of these findings are discussed.

PMID- 24141102
TI  - A rare case of abdominal cocoon.
AB  - AIM: Abdominal cocoon is a rare cause of intestinal obstruction usually diagnosed
      incidentally at laparotomy. It manifests by forming a membrane that typically
      encases the small bowel loops, leading to mechanical obstruction. Preoperative
      diagnosis is difficult. The etiology of this condition is not well understood;
      however, it is a form of chronic irritation and inflammation. METHOD: A 33 years
      old male, from Bangladesh, presented to our emergency department complaining of
      abdominal pain, nausea, and vomiting. CT abdomen shows a picture of intestinal
      obstruction at the level of the small intestine. Intraoperative findings showed
      encapsulation of small bowel by a dense whitish membrane as a cocoon.
      Histological examination showed a granulomatous peritonitis and Ascaris
      Lumbricoides in the bowel resected. RESULTS AND CONCLUSIONS: The preoperative
      diagnosis of abdominal cocoon is difficult and hence, the diagnosis is usually
      confirmed by laparotomy. Surgery remains the cornerstone in the management of
      abdominal cocoon. The pathogenesis of abdominal cocoon remains elusive and has
      been associated with several conditions. The initial diagnosis of our patient was
      bowel obstruction from cocoon syndrome (CT and intraoperative findings) probably
      primitive, and only histologically proved granulomatous peritonitis associated
      with the presence of the parasite.

PMID- 24141096
TI  - Highlights of the DNA cutters: a short history of the restriction enzymes.
AB  - In the early 1950's, 'host-controlled variation in bacterial viruses' was
      reported as a non-hereditary phenomenon: one cycle of viral growth on certain
      bacterial hosts affected the ability of progeny virus to grow on other hosts by
      either restricting or enlarging their host range. Unlike mutation, this change
      was reversible, and one cycle of growth in the previous host returned the virus
      to its original form. These simple observations heralded the discovery of the
      endonuclease and methyltransferase activities of what are now termed Type I, II,
      III and IV DNA restriction-modification systems. The Type II restriction enzymes
      (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed
      molecular biology and medicine. This review traces the discovery of restriction
      enzymes and their continuing impact on molecular biology and medicine. 

PMID- 24141103
TI  - Effect of sports modification on clinical outcome in children and adolescent
      athletes with symptomatic lumbar spondylolysis.
AB  - OBJECTIVE: This cohort study aimed to report the compliance of young athletes
      with nonoperative treatment and to clarify the role of sports modification on
      clinical outcome of symptomatic spondylolysis. DESIGN: This study included
      patients with a chief complaint of low back pain participating in regular sports
      activity, having spondylolysis, and being treated and followed up between 1990
      and 2002 in the authors' hospital. RESULTS: One hundred thirty-two athletes were
      included in this study: 78 males and 54 females. The mean age of the patients was
      13 yrs (range, 7-18 yrs). Only 56 patients (42.4%) were compliant to nonoperative
      treatment. Eighty-six patients (65%) stopped all sports activities for at least 3
      mos, and 46 patients (35%) stopped exercising for a variable period of less than
      3 mos. The grading of clinical outcome after nonoperative treatment was as
      follows: excellent in 48 patients (36.4%), good in 74 patients (56.1), fair in 6
      patients (4.5%), and poor in 4 patients (3%). The patients who stopped sports for
      at least 3 mos were 16.39 times more likely to have an excellent result than
      those who did not stop sports. Bony healing on radiographs did not correlate with
      clinical outcome. CONCLUSIONS: Timely cessation of sports activity for 3 mos is
      considered an effective method of nonoperative treatment for young athletes with
      symptomatic lumbar spondylolysis.

PMID- 24141104
TI  - Particle disease osteolysis of the pelvis and the hip after hip arthroplasty.

PMID- 24141105
TI  - Forgotten denture in a hemiplegic patient.
AB  - A 74-yr-old man developed left hemiplegia because of a right middle cerebral
      artery territory infarction and also had clinical features of dysphagia and
      speech difficulty. At that time, he complained of neck pain, but the symptom was
      ignored because he had a nasogastric tube and had been diagnosed with a huge
      epiglottic cyst that had already shown several symptoms such as severe hoarseness
      and throat discomfort. A videofluoroscopic swallowing study was planned to find
      out the cause and the type of dysphagia. On the videofluoroscopic swallowing
      study, a foreign body was found at the hypopharynx. Surprisingly, it was
      confirmed as a denture. After removing the denture, the patient's swallowing and
      speech difficulty were significantly improved. This case emphasizes the need for
      elderly stoke patients presenting with dysphagia or communication problems to
      receive more careful history taking and a more complete physical examination,
      with the cooperation of several clinical departments. 

PMID- 24141106
TI  - A conservative vapour intrusion screening model of oxygen-limited hydrocarbon
      vapour biodegradation accounting for building footprint size.
AB  - Petroleum hydrocarbon vapours pose a reduced risk to indoor air due to
      biodegradation processes where oxygen is available in the subsurface or below
      built structures. However, no previous assessment has been available to show the
      effects of a building footprint (slab size) on oxygen-limited hydrocarbon vapour
      biodegradation and the potential for oxygen to be present beneath the entire sub
      slab region of a building. Here we provide a new, conservative and conceptually
      simple vapour screening model which links oxygen and hydrocarbon vapour transport
      and biodegradation in the vicinity and beneath an impervious slab. This defines
      when vapour risk is insignificant, or conversely when there is potential for
      vapour to contact the sub-slab of a building. The solution involves complex
      mathematics to determine the position of an unknown boundary interface between
      oxygen diffusing in from the ground surface and vapours diffusing upwards from a
      subsurface vapour source, but the mathematics reduces to a simple relationship
      between the vapour source concentration and the ratio of the half slab width and
      depth to the vapour source. Data from known field investigations are shown to be
      consistent with the model predictions. Examples of 'acceptable' slab sizes for
      vapour source depths and strengths are given. The predictions are conservative as
      an estimator of when petroleum hydrocarbon vapours might come in contact with a
      slab-on-ground building since additional sources of oxygen due to advective flow
      or diffusion through the slab are ignored. As such the model can be used for
      screening sites for further investigation. 

PMID- 24141107
TI  - The glia doctrine: addressing the role of glial cells in healthy brain ageing.
AB  - Glial cells in their plurality pervade the human brain and impact on brain
      structure and function. A principal component of the emerging glial doctrine is
      the hypothesis that astrocytes, the most abundant type of glial cells, trigger
      major molecular processes leading to brain ageing. Astrocyte biology has been
      examined using molecular, biochemical and structural methods, as well as 3D brain
      imaging in live animals and humans. Exosomes are extracelluar membrane vesicles
      that facilitate communication between glia, and have significant potential for
      biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may
      indirectly influence the structure and function of membrane proteins expressed in
      glial cells and predispose specific cell subgroups to degeneration. Physical
      exercise may reduce or retard age-related brain deterioration by a mechanism
      involving neuro-glial processes. It is most likely that additional information
      about the distribution, structure and function of glial cells will yield novel
      insight into human brain ageing. Systematic studies of glia and their functions
      are expected to eventually lead to earlier detection of ageing-related brain
      dysfunction and to interventions that could delay, reduce or prevent brain
      dysfunction. 

PMID- 24141108
TI  - uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human
      pancreatic tumors.
AB  - Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The
      identification of therapies that can eliminate this population of cells might
      provide with more effective treatments. In the current work we evaluated the
      potential of oncolytic adenoviruses to act against pancreatic cancer stem cells
      (PCSC). PCSC from two patient-derived xenograft models were isolated from
      orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic
      agent gemcitabine. An enrichment in the number of PCSC expressing the cell
      surface marker CD133 and a marked enhancement on tumorsphere formation was
      observed in gemcitabine treated tumors. No significant increase in the CD44,
      CD24, and epithelial-specific antigen (ESA) positive cells was observed.
      Neoplastic sphere-forming cells were susceptible to adenoviral infection and
      exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both
      Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous
      administration of a single dose of AduPARE1A in human-derived pancreatic
      xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine
      AduPARE1A treatment did not result in PCSC enrichment. No enrichment on
      tumorspheres neither on the CD133(+) population was detected. Therefore our data
      provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for
      the elimination of pancreatic cancer stem cells. 

PMID- 24141109
TI  - Hydrogel formulation determines cell fate of fetal and adult neural progenitor
      cells.
AB  - Hydrogels provide a unique tool for neural tissue engineering. These materials
      can be customized for certain functions, i.e. to provide cell/drug delivery or
      act as a physical scaffold. Unfortunately, hydrogel complexities can negatively
      impact their biocompatibility, resulting in unintended consequences. These
      adverse effects may be combated with a better understanding of hydrogel chemical,
      physical, and mechanical properties, and how these properties affect encapsulated
      neural cells. We defined the polymerization and degradation rates and compressive
      moduli of 25 hydrogels formulated from different concentrations of hyaluronic
      acid (HA) and poly(ethylene glycol) (PEG). Changes in compressive modulus were
      driven primarily by the HA concentration. The in vitro biocompatibility of fetal
      derived (fNPC) and adult-derived (aNPC) neural progenitor cells was dependent on
      hydrogel formulation. Acute survival of fNPC benefited from hydrogel
      encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly
      glial cells, compared with neuronal differentiation of aNPC. Differentiation was
      influenced in part by the hydrogel mechanical properties. This study indicates
      that there can be a wide range of HA and PEG hydrogels compatible with NPC.
      Additionally, this is the first study comparing hydrogel encapsulation of NPC
      derived from different aged sources, with data suggesting that fNPC and aNPC
      respond dissimilarly within the same hydrogel formulation. 

PMID- 24141110
TI  - HIF1alpha is a regulator of hematopoietic progenitor and stem cell development in
      hypoxic sites of the mouse embryo.
AB  - Hypoxia affects many physiologic processes during early stages of mammalian
      ontogeny, particularly placental and vascular development. In the adult, the
      hypoxic bone marrow microenvironment plays a role in regulating hematopoietic
      stem cell (HSC) function. HSCs are generated from the major vasculature of the
      embryo, but whether the hypoxic response affects the generation of these HSCs is
      as yet unknown. Here we examined whether Hypoxia Inducible Factor1-alpha
      (HIF1alpha), a key modulator of the response to hypoxia, is essential for HSC
      development. We found hypoxic cells in embryonic tissues that generate and expand
      hematopoietic cells (aorta, placenta and fetal liver), and specifically aortic
      endothelial and hematopoietic cluster cells. A Cre/loxP conditional knockout
      (cKO) approach was taken to delete HIF1alpha in Vascular Endothelial-Cadherin
      expressing endothelial cells, the precursors to definitive hematopoietic cells.
      Functional assays show that HSC and hematopoietic progenitor cells (HPCs) are
      significantly reduced in cKO aorta and placenta. Moreover, decreases in
      phenotypic aortic hematopoietic cluster cells in cKO embryos indicate that
      HIF1alpha is necessary for generation and/or expansion of HPCs and HSCs. cKO
      adult BM HSCs are also affected under transplantation conditions. Thus, HIF1alpha
      is a regulator of HSC generation and function beginning at the earliest embryonic
      stages. 

PMID- 24141111
TI  - Selective antitumor effect of neural stem cells expressing cytosine deaminase and
      interferon-beta against ductal breast cancer cells in cellular and xenograft
      models.
AB  - Due to their inherent tumor-tropic properties, genetically engineered stem cells
      may be advantageous for gene therapy treatment of various human cancers,
      including brain, liver, ovarian, and prostate malignancies. In this study, we
      employed human neural stem cells (HB1.F3; hNSCs) transduced with genes expressing
      Escherichia coli cytosine deaminase (HB1.F3.CD) and human interferon-beta
      (HB1.F3.CD.IFN-beta) as a treatment strategy for ductal breast cancer. CD can
      convert the prodrug 5-fluorocytosine (5-FC) to its active chemotherapeutic form,
      5-fluorouracil (5-FU), which induces a tumor-killing effect through DNA synthesis
      inhibition. IFN-beta also strongly inhibits tumor growth by the apoptotic
      process. RT-PCR confirmed that HB1.F3.CD cells expressed CD and HB1.F3.CD.IFN
      beta cells expressed both CD and IFN-beta. A modified transwell migration assay
      showed that HB1.F3.CD and HB1.F3.CD.IFN-beta cells selectively migrated toward
      MCF-7 and MDA-MB-231 human breast cancer cells. In hNSC-breast cancer co-cultures
      the viability of breast cancer cells which were significantly reduced by
      HB1.F3.CD or HB1.F3.CD.IFN-beta cells in the presence of 5-FC. The tumor
      inhibitory effect was greater with the HB1.F3.CD.IFN-beta cells, indicating an
      additional effect of IFN-beta to 5-FU. In addition, the tumor-tropic properties
      of these hNSCs were found to be attributed to chemoattractant molecules secreted
      by breast cancer cells, including stem cell factor (SCF), c-kit, vascular
      endothelial growth factor (VEGF), and VEGF receptor 2. An in vivo assay performed
      using MDA-MB-231/luc breast cancer mammary fat pad xenografts in immunodeficient
      mice resulted in 50% reduced tumor growth and increased long-term survival in
      HB1.F3.CD and HB1.F3.CD.IFN-beta plus 5-FC treated mice relative to controls. Our
      results suggest that hNSCs genetically modified to express CD and/or IFN-beta
      genes can be used as a novel targeted cancer gene therapy. 

PMID- 24141112
TI  - Signal-on photoelectrochemical biosensor for microRNA detection based on Bi2S3
      nanorods and enzymatic amplification.
AB  - In this work, a photoelectrochemical (PEC) biosensor was fabricated for sensitive
      and specific detection of microRNA based on Bi2S3 nanorods and enzymatic signal
      amplification. Using the catalytic effect of alkaline phosphatase on l-ascorbic
      acid 2-phosphate trisodium salt (AAP), ascorbic acid (AA) was in situ generated
      and used as electron donor. Based on this, a signal-on protocol was successively
      achieved for microRNAs detection due to the dependence of photocurrent response
      on the concentration of electron donor of AA. The results demonstrated that the
      photocurrent response enhanced with increasing the hybridized concentration of
      microRNA. Under the amplification of the immunogold labeled streptavidin (SA
      AuNPs), a low detection limit of 1.67 fM was obtained. The fabricated biosensor
      showed good detection stability and specificity, and it could discriminate only
      one-base mismatched microRNA sequence. Moreover, the down-regulated expression of
      microRNA-21 in DF-1 chicken fibroblast cells infected with subgroup J avian
      leukemia virus (ALVs) was confirmed by the developed method, indicating that
      microRNA-21 might be a new biomarker for avian leukemia. This work opens a
      different perspective for microRNAs detection and early diagnose of avian
      leukemia.

PMID- 24141113
TI  - Simple approach for ultrasensitive electrochemical immunoassay of Clostridium
      difficile toxin B detection.
AB  - Clostridium difficile toxin B (Tcd B), as one of the primary contributing factors
      to the pathogenesis of C. difficile-associated diseases, has raised serious
      public concerns due to its virulence, spore-forming ability and persistence with
      major types of infectious diarrhea diseases, and been used as a potential
      biomarker in clinical diagnoses. Thus, a simple method for the determination of
      Tcd B was developed based on a sandwich-type electrochemical immunosensor.
      Greatly enhanced sensitivity was achieved based on fabricating the immunosensor
      by layer-by-layer coating carbon nanotubes (MWCNTs), Prussian blue (PB), Chitosan
      (CS), Glutaraldehyde (GA) composite on the working electrode as well as using
      graphene oxide (GO) as a nanocarrier in a multienzyme amplification strategy. In
      comparison with conventional methods, the proposed immunoassay exhibited high
      sensitivity and selectivity for the detection of Tcd B, providing a better linear
      response range from 0.003 to 320 ng/mL and a lower limit of detection (LOD) of
      0.7 pg/mL (S/N=3) under optimal experimental conditions. The immunosensor
      exhibited convenience, low cost, rapidity, good specificity, acceptable stability
      and reproducibility. Moreover, satisfactory results were obtained for the
      determination of Tcd B in real human stool samples, indicating that the developed
      immunoassay has the potential to find application in clinical detection of Tcd B
      and other tumor markers as an alternative approach.

PMID- 24141114
TI  - DNA methyltransferase activity assay based on visible light-activated
      photoelectrochemical biosensor.
AB  - DNA methylation has important roles in gene regulation and relates to some
      diseases, especially cancers. Because DNA methylation is catalyzed by DNA
      methyltransferases (MTase), it is important to detect the activity of DNA MTase.
      In this work, we developed a novel visible light-activated photoelectrochemical
      (PEC) biosensor for DNA MTase activity assay, whereby bismuth oxyiodide (BiOI)
      nanoflake was synthesized as photoactive electrode material, M. SssI MTase as
      methylation reagent and methyl binding domain protein (MBD1 protein) as
      methylation recognition element. After cytosine methylation event occurred at the
      site of 5'-CG-3', it could be probed by MBD1 protein and this protein could be
      combined tightly with methylated cytosine, which would lead to a decreased
      photocurrent due to the hindrance towards electron donor transferring to
      electrode surface by huge-volume protein. The decreased photocurrent was
      proportional to M. SssI MTase concentration from 0.1 to 50 unit/mL with the
      detection limit of 0.035 unit/mL (S/N=3). This detection limit was lower than
      that in some previous reports. This PEC biosensor showed high selectivity and
      good reproducibility for M. SssI MTase assay. Moreover, this method was
      successfully applied also to screen DNA MTase inhibitors, indicating that this
      PEC biosensor could be an alternative platform in anti-cancer pharmaceuticals
      discovery.

PMID- 24141115
TI  - Intraoperative finding of Amyand's hernia in a recurrent inguinal hernia: report
      of a case.
AB  - INTRODUCTION: The finding of the vermiform appendix within an inguinal hernia is
      a rare entity 2,3. An inflamed or non-inflamed vermiform appendix in an inguinal
      hernia sac is named Amyand's hernia in honor to the surgeon Claudius Amyand who
      published the first case of perforated appendicitis within inguinal hernia in a
      boy caused by ingested pin. OBJECTIVE: The aim of this study was to report our
      intraoperative findings with this entity. MATERIAL AND METHODS: We report a case
      of 47 year old male patient with a recurrent right inguinal hernia. We were not
      able to review the previous operative notes . The patient underwent an elective
      redo-redo inguinal hernia repair under local anesthesia with I.V. sedation; a
      normal appearing appendix with an adhesive plug were explored within a direct
      hernia sac. Adhesions were divided by sharp dissection, an appendectomy was
      performed and the plug excised. A modified Bassini repair was performed and the
      patient admitted to the hospital. RESULTS: The patient's postoperative course was
      unremarkable; he was discharged home on postoperative day 3. At one week follow
      up we found no complications. CONCLUSION: The finding of the appendix in an
      inguinal hernia is a rare entity that is difficult to diagnose preoperatively.
      Treatment includes appendectomy and herniorraphy. The use of prosthetic mesh
      depends on the status of the appendix, patient's condition and hernia findings.

PMID- 24141116
TI  - Enhancement of mitochondrial function correlates with the extension of lifespan
      by caloric restriction and caloric restriction mimetics in yeast.
AB  - Caloric restriction mimetics (CRMs) have been developed to mimic the effects of
      caloric restriction (CR). However, research reports for the effects of CRMs are
      often times inconsistent across different research groups. Therefore, in this
      study, we compared seven identified CRMs which extend the lifespans of various
      organisms including caffeine, curcumin, dapsone, metformin, rapamycin,
      resveratrol, and spermidine to CR for mitochondrial function in a single model,
      Saccharomyces cerevisiae. In this organism, rapamycin extended chronological
      lifespan (CLS), but other CRMs failed to extend CLS. Rapamycin enhanced
      mitochondrial function like CR did, but other CRMs did not. Both CR and rapamycin
      worked on mitochondrial function, but they worked at different windows of time
      during the chronological aging process. 

PMID- 24141117
TI  - An efficient method for organic acetylation and use of DL-phosphinothricin as a
      negative selection agent in argE transgenic rice.
AB  - We present an efficient method for the production of N-acetyl-L-phosphinothricin
      (N-AcPt) from commercial DL-phosphinothricin (DL-PPT) by organic acetylation for
      use as a negative selection agent (NSA) that induces cell death in argE
      transgenic rice. DL-PPT was efficiently converted into N-AcPt with
      tetrahydrofuran (THF) and acetic anhydride (Ac2O). Chemical changes were
      confirmed using NMR and ATR-FTIR analyses. DL-PPT was toxic but N-AcPt did not
      show cytotoxic effects on leaf discs or seed germination of wild-type rice.
      Conversely, in argE-hpt transgenic rice, non-toxic N-AcPt showed the negative
      selection (NS) effect by inducing cell destruction in leaf discs and restricting
      seed germination. For inducing NS, >=0.1 mg ml(-1) and >=0.5 mg ml(-1) of N-AcPt
      were effective in leaf and seed assays, respectively. Further, the NS effect
      occurred faster in the leaf assay compared with the seed germination assay, again
      indicating the leaf assay was a more sensitive indicator of N-AcPt as an NSA to
      argE transgenic rice than the seed germination assay. This negative selection
      approach could be useful for the development of selectable marker free transgenic
      plants in the economically important monocot species and its commercialization
      for multiple gene transformation.

PMID- 24141118
TI  - Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from
      osteoarthritic cartilage through up-regulation of extracellular signal-regulated
      kinase 1/2 and suppression of FASL, FAS, and Caspase 3.
AB  - Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti
      inflammatory and analgesic effect. However, Dex also has many side effects
      following repeated use over prolonged periods mainly through increasing apoptosis
      and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic
      effect on many cells and little is known about its effect on OA chondrocytes.
      Therefore, the aim of this study is to investigate whether LF can inhibit Dex
      induced OA chondrocytes apoptosis and explore its possible molecular mechanism
      involved in. MTT assay was used to determine the optimal concentration of Dex and
      recombinant human LF (rhLF) on chondrocytes at different time and dose points.
      Chondrocytes were then stimulated with Dex in the absence or presence of optimal
      concentration of rhLF. Cell proliferation and viability were evaluated using MTT
      and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi
      parameter apoptosis assay kit using both confocal microscopy and flow cytometry,
      respectively. The expression of extracellular signal-regulated kinase (ERK), FAS,
      FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real
      time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The
      optimal concentration of Dex (25 MUg/ml) and rhLF (200 MUg/ml) were chosen for
      the following experiments. rhLF significantly reversed the detrimental effect of
      Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF
      significantly prevented Dex-induced down-regulation of ERK and up-regulation of
      FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as an anabolic
      effect on chondrocytes through significantly reversing Dex-induced chondrocytes
      apoptosis. This study may contribute to further investigating the clinical
      application of LF on OA.

PMID- 24141119
TI  - The thiol proteinase inhibitor E-64-d ameliorates amyloid-beta-induced reduction
      of sAPPalpha secretion by reversing ceramide-induced protein kinase C down
      regulation in SH-SY5Y neuroblastoma cells.
AB  - In Alzheimer's disease (AD), enhancing alpha-secretase processing of amyloid
      precursor protein (APP) is an important pathway to decrease neurotoxic amyloid
      beta (Abeta) secretion. The alpha-secretase is reported to be regulated by
      protein kinase C (PKC) and various endogenous proteins or cell surface receptors.
      In this report, we first examined whether Abeta reduces alpha-secretase activity,
      and showed that Abeta peptide 1-40 (0.001 and 0.01 MUM) reduced the secretion of
      soluble amyloid precursor protein alpha (sAPPalpha) in carbachol-stimulated SH
      SY5Y neuroblastoma cells. E-64-d (3 MUM), which is a potent calpain inhibitor
      that prevents PKC degradation, ameliorated the Abeta-induced reduction of
      sAPPalpha secretion. In addition, we observed that Abeta significantly enhanced
      ceramide production by activating neutral sphingomyelinase. The cell-permeable
      ceramide analog, C2-ceramide (1 MUg/mL), also reduced sAPPalpha secretion, and in
      addition, E-64-d eliminated the observed decrease of sAPPalpha secretion. C2
      ceramide induced down-regulation of PKC-alpha, -beta1, and -beta2 isozymes in SH
      SY5Y cells. These findings suggest that ceramide may play an important role in
      sAPPalpha processing by modulating PKC activity.

PMID- 24141120
TI  - Nonclinical and clinical Enterococcus faecium strains, but not Enterococcus
      faecalis strains, have distinct structural and functional genomic features.
AB  - Certain strains of Enterococcus faecium and Enterococcus faecalis contribute
      beneficially to animal health and food production, while others are associated
      with nosocomial infections. To determine whether there are structural and
      functional genomic features that are distinct between nonclinical (NC) and
      clinical (CL) strains of those species, we analyzed the genomes of 31 E. faecium
      and 38 E. faecalis strains. Hierarchical clustering of 7,017 orthologs found in
      the E. faecium pangenome revealed that NC strains clustered into two clades and
      are distinct from CL strains. NC E. faecium genomes are significantly smaller
      than CL genomes, and this difference was partly explained by significantly fewer
      mobile genetic elements (ME), virulence factors (VF), and antibiotic resistance
      (AR) genes. E. faecium ortholog comparisons identified 68 and 153 genes that are
      enriched for NC and CL strains, respectively. Proximity analysis showed that CL
      enriched loci, and not NC-enriched loci, are more frequently colocalized on the
      genome with ME. In CL genomes, AR genes are also colocalized with ME, and VF are
      more frequently associated with CL-enriched loci. Genes in 23 functional groups
      are also differentially enriched between NC and CL E. faecium genomes. In
      contrast, differences were not observed between NC and CL E. faecalis genomes
      despite their having larger genomes than E. faecium. Our findings show that
      unlike E. faecalis, NC and CL E. faecium strains are equipped with distinct
      structural and functional genomic features indicative of adaptation to different
      environments. 

PMID- 24141121
TI  - Toxicity of bioactive and probiotic marine bacteria and their secondary
      metabolites in Artemia sp. and Caenorhabditis elegans as eukaryotic model
      organisms.
AB  - We have previously reported that some strains belonging to the marine
      Actinobacteria class, the Pseudoalteromonas genus, the Roseobacter clade, and the
      Photobacteriaceae and Vibrionaceae families produce both antibacterial and
      antivirulence compounds, and these organisms are interesting from an applied
      point of view as fish probiotics or as a source of pharmaceutical compounds. The
      application of either organisms or compounds requires that they do not cause any
      side effects, such as toxicity in eukaryotic organisms. The purpose of this study
      was to determine whether these bacteria or their compounds have any toxic side
      effects in the eukaryotic organisms Artemia sp. and Caenorhabditis elegans.
      Arthrobacter davidanieli WX-11, Pseudoalteromonas luteoviolacea S4060, P.
      piscicida S2049, P. rubra S2471, Photobacterium halotolerans S2753, and Vibrio
      coralliilyticus S2052 were lethal to either or both model eukaryotes. The
      toxicity of P. luteoviolacea S4060 could be related to the production of the
      antibacterial compound pentabromopseudilin, while the adverse effect observed in
      the presence of P. halotolerans S2753 and V. coralliilyticus S2052 could not be
      explained by the production of holomycin nor andrimid, the respective antibiotic
      compounds in these organisms. In contrast, the tropodithietic acid (TDA)
      producing bacteria Phaeobacter inhibens DSM17395 and Ruegeria mobilis F1926 and
      TDA itself had no adverse effect on the target organisms. These results reaffirm
      TDA-producing Roseobacter bacteria as a promising group to be used as probiotics
      in aquaculture, whereas Actinobacteria, Pseudoalteromonas, Photobacteriaceae, and
      Vibrionaceae should be used with caution. 

PMID- 24141123
TI  - Transferable denitrification capability of Thermus thermophilus.
AB  - Laboratory-adapted strains of Thermus spp. have been shown to require oxygen for
      growth, including the model strains T. thermophilus HB27 and HB8. In contrast,
      many isolates of this species that have not been intensively grown under
      laboratory conditions keep the capability to grow anaerobically with one or more
      electron acceptors. The use of nitrogen oxides, especially nitrate, as electron
      acceptors is one of the most widespread capabilities among these facultative
      strains. In this process, nitrate is reduced to nitrite by a reductase (Nar) that
      also functions as electron transporter toward nitrite and nitric oxide reductases
      when nitrate is scarce, effectively replacing respiratory complex III. In many T.
      thermophilus denitrificant strains, most electrons for Nar are provided by a new
      class of NADH dehydrogenase (Nrc). The ability to reduce nitrite to NO and
      subsequently to N2O by the corresponding Nir and Nor reductases is also strain
      specific. The genes encoding the capabilities for nitrate (nar) and nitrite (nir
      and nor) respiration are easily transferred between T. thermophilus strains by
      natural competence or by a conjugation-like process and may be easily lost upon
      continuous growth under aerobic conditions. The reason for this instability is
      apparently related to the fact that these metabolic capabilities are encoded in
      gene cluster islands, which are delimited by insertion sequences and integrated
      within highly variable regions of easily transferable extrachromosomal elements.
      Together with the chromosomal genes, these plasmid-associated genetic islands
      constitute the extended pangenome of T. thermophilus that provides this species
      with an enhanced capability to adapt to changing environments. 

PMID- 24141122
TI  - Single-cell analyses revealed transfer ranges of IncP-1, IncP-7, and IncP-9
      plasmids in a soil bacterial community.
AB  - The conjugative transfer ranges of three different plasmids of the
      incompatibility groups IncP-1 (pBP136), IncP-7 (pCAR1), and IncP-9 (NAH7) were
      investigated in soil bacterial communities by culture-dependent and culture
      independent methods. Pseudomonas putida, a donor of each plasmid, was mated with
      soil bacteria, and green fluorescent protein (GFP), encoded on the plasmid, was
      used as a reporter protein for successful transfer. GFP-expressing
      transconjugants were detected and separated at the single-cell level by flow
      cytometry. Each cell was then analyzed by PCR and sequencing of its 16S rRNA gene
      following either whole-genome amplification or cultivation. A large number of
      bacteria within the phylum Proteobacteria was identified as transconjugants for
      pBP136 by both culture-dependent and culture-independent methods. Transconjugants
      belonging to the phyla Actinobacteria, Bacteroidetes, and Firmicutes were
      detected only by the culture-independent method. Members of the genus Pseudomonas
      (class Gammaproteobacteria) were identified as major transconjugants of pCAR1 and
      NAH7 by both methods, whereas Delftia species (class Betaproteobacteria) were
      detected only by the culture-independent method. The transconjugants represented
      a minority of the soil bacteria. Although pCAR1-containing Delftia strains could
      not be cultivated after a one-to-one filter mating assay between the donor and
      cultivable Delftia strains as recipients, fluorescence in situ hybridization
      detected pCAR1-containing Delftia cells, suggesting that Delftia was a
      "transient" host of pCAR1. 

PMID- 24141124
TI  - The ability of bifidobacteria to degrade arabinoxylan oligosaccharide
      constituents and derived oligosaccharides is strain dependent.
AB  - Arabinoxylan oligosaccharides (AXOS) are prebiotic carbohydrates with promising
      health-promoting properties that stimulate the activity of specific colon
      bacteria, in particular bifidobacteria. However, the mechanisms by which
      bifidobacterial strains break down these compounds in the colon is still unknown.
      This study investigates AXOS consumption of a large number of bifidobacterial
      strains (36), belonging to 11 different species, systematically. To determine
      their degradation mechanisms, all strains were grown on a mixture of arabinose
      and xylose, xylo-oligosaccharides, and complex AXOS molecules as the sole added
      energy sources. Based on principal component and cluster analyses of their
      different arabinose substituent and/or xylose backbone consumption patterns, five
      clusters that were species independent could be distinguished among the
      bifidobacterial strains tested. In parallel, the strains were screened for the
      presence of genes encoding several putative AXOS-degrading enzymes, but no clear
      cut correlation could be made with the different degradation mechanisms. The
      intra- and interspecies differences in the consumption patterns of AXOS indicate
      that bifidobacterial strains could avoid competition among each other or even
      could cooperate jointly to degrade these complex prebiotics. The knowledge gained
      on the AXOS degradation mechanisms in bifidobacteria can be of importance in the
      rational design of prebiotics with tailor-made composition and thus increased
      specificity in the colon. 

PMID- 24141125
TI  - Microbiomes of unreactive and pathologically altered ileocecal lymph nodes of
      slaughter pigs.
AB  - Microbe-laden dendritic cells are shifted to ileocecal lymph nodes (ICLNs), where
      microbes are concentrated and an adequate immune response is triggered. Hence,
      ICLNs are at a crucial position in immune anatomy and control processes of the
      local immune system. Pathological alterations in ICLNs, such as reactive
      hyperplasia, lymphadenitis purulenta, or granulomatosa, can harbor a multitude of
      pathogens and commensals, posing a potential zoonotic risk in animal production.
      The aim of this study was to characterize the microbial diversity of unreactive
      ICLNs of slaughter pigs and to investigate community shifts in reactive ICLNs
      altered by enlargement, purulence, or granulomatous formations. Pyrosequencing of
      16S rRNA gene amplicons from 32 ICLNs yielded 175,313 sequences, clustering into
      650 operational taxonomic units (OTUs). OTUs were assigned to 239 genera and 11
      phyla. Besides a highly diverse bacterial community in ICLNs, we observed
      significant shifts in pathologically altered ICLNs. The relative abundances of
      Cloacibacterium- and Novosphingobium-associated OTUs and the genus
      Faecalibacterium were significantly higher in unreactive ICLNs than in
      pathologically altered ICLNs. Enlarged ICLNs harbored significantly more
      Lactobacillus- and Clostridium-associated sequences. Relative abundances of
      Mycoplasma, Bacteroides, Veillonella, and Variovorax OTUs were significantly
      increased in granulomatous ICLNs, whereas abundances of Pseudomonas, Escherichia,
      and Acinetobacter OTUs were significantly increased in purulent ICLNs (P < 0.05).
      Correlation-based networks revealed interactions among OTUs in all ICLN groups,
      and discriminant analyses depicted discrimination in response to pathological
      alterations. This study is the first community-based survey in ICLNs of livestock
      animals and will provide a basis to broaden the knowledge of microbe-host
      interactions in pigs. 

PMID- 24141126
TI  - Synthetic promoters functional in Francisella novicida and Escherichia coli.
AB  - In this work, we describe the identification of synthetic, controllable promoters
      that function in the bacterial pathogen Francisella novicida, a model facultative
      intracellular pathogen. Synthetic DNA fragments consisting of the tetracycline
      operator (tetO) flanked by a random nucleotide sequence were inserted into a
      Francisella novicida shuttle plasmid upstream of a promoterless artificial operon
      containing the reporter genes cat and lacZ. Fragments able to promote
      transcription were selected for based on their ability to drive expression of the
      cat gene, conferring chloramphenicol resistance. Promoters of various strengths
      were found, many of which were repressed in the presence of the tetracycline
      repressor (TetR) and promoted transcription only in the presence of the TetR
      inducer anhydrotetracycline. A subset of both constitutive and inducible
      synthetic promoters were characterized to find their induction ratios and to
      identify their transcription start sites. In cases where tetO was located between
      or downstream of the -10 and -35 regions of the promoter, control by TetR was
      observed. If the tetO region was upstream of the -35 region by more than 9 bp, it
      did not confer TetR control. We found that three of three promoters isolated in
      F. novicida functioned at a comparable level in E. coli; however, none of the 10
      promoters isolated in E. coli functioned at a significant level in F. novicida.
      Our results allowed us to isolate minimal F. novicida promoters of 47 and 48 bp
      in length. 

PMID- 24141127
TI  - Novel characteristics of succinate coenzyme A (Succinate-CoA) ligases: conversion
      of malate to malyl-CoA and CoA-thioester formation of succinate analogues in
      vitro.
AB  - Three succinate coenzyme A (succinate-CoA) ligases (SucCD) from Escherichia coli,
      Advenella mimigardefordensis DPN7(T), and Alcanivorax borkumensis SK2 were
      characterized regarding their substrate specificity concerning succinate
      analogues. Previous studies had suggested that SucCD enzymes might be promiscuous
      toward succinate analogues, such as itaconate and 3-sulfinopropionate (3SP). The
      latter is an intermediate of the degradation pathway of 3,3'-dithiodipropionate
      (DTDP), a precursor for the biotechnical production of polythioesters (PTEs) in
      bacteria. The sucCD genes were expressed in E. coli BL21(DE3)/pLysS. The SucCD
      enzymes of E. coli and A. mimigardefordensis DPN7(T) were purified in the native
      state using stepwise purification protocols, while SucCD from A. borkumensis SK2
      was equipped with a C-terminal hexahistidine tag at the SucD subunit. Besides the
      preference for the physiological substrates succinate, itaconate, ATP, and CoA,
      high enzyme activity was additionally determined for both enantiomeric forms of
      malate, amounting to 10 to 21% of the activity with succinate. Km values ranged
      from 2.5 to 3.6 mM for l-malate and from 3.6 to 4.2 mM for d-malate for the SucCD
      enzymes investigated in this study. As l-malate-CoA ligase is present in the
      serine cycle for assimilation of C1 compounds in methylotrophs, structural
      comparison of these two enzymes as members of the same subsubclass suggested a
      strong resemblance of SucCD to l-malate-CoA ligase and gave rise to the
      speculation that malate-CoA ligases and succinate-CoA ligases have the same
      evolutionary origin. Although enzyme activities were very low for the additional
      substrates investigated, liquid chromatography/electrospray ionization-mass
      spectrometry analyses proved the ability of SucCD enzymes to form CoA-thioesters
      of adipate, glutarate, and fumarate. Since all SucCD enzymes were able to
      activate 3SP to 3SP-CoA, we consequently demonstrated that the activation of 3SP
      is not a unique characteristic of the SucCD from A. mimigardefordensis DPN7(T).
      The essential role of sucCD in the activation of 3SP in vivo was proved by
      genetic complementation. 

PMID- 24141128
TI  - Host specificity and source of Enterocytozoon bieneusi genotypes in a drinking
      source watershed.
AB  - To assess the host specificity of Enterocytozoon bieneusi and to track the
      sources of E. bieneusi contamination, we genotyped E. bieneusi in wildlife and
      stormwater from the watershed of New York City's source water, using ribosomal
      internal transcribed spacer (ITS)-based PCR and sequence analyses. A total of 255
      specimens from 23 species of wild mammals and 67 samples from stormwater were
      analyzed. Seventy-four (29.0%) of the wildlife specimens and 39 (58.2%) of the
      stormwater samples from streams were PCR positive. Altogether, 20 E. bieneusi
      genotypes were found, including 8 known genotypes and 12 new ones. Sixteen and
      five of the genotypes were seen in animals and stormwater from the watershed,
      respectively, with WL4 being the most common genotype in both animals (35
      samples) and stormwater (23 samples). The 20 E. bieneusi genotypes belonged to
      five genogroups (groups 1, 3, 4, and 7 and an outlier), with only 23/113 (20.4%)
      E. bieneusi-positive samples belonging to zoonotic genogroup 1 and 3/20 genotypes
      ever being detected in humans. The two genogroups previously considered host
      specific, groups 3 and 4, were both detected in multiple groups of mammals. Thus,
      with the exception of the type IV, Peru11, and D genotypes, which were detected
      in only 7, 5, and 2 animals, respectively, most E. bieneusi strains in most
      wildlife samples and all stormwater samples in the watershed had no known public
      health significance, as these types have not previously been detected in humans.
      The role of different species of wild mammals in the contribution of E. bieneusi
      contamination in stormwater was supported by determinations of host-adapted
      Cryptosporidium species/genotypes in the same water samples. Data from this study
      indicate that the host specificity of E. bieneusi group 3 is broader than
      originally thought, and wildlife is the main source of E. bieneusi in stormwater
      in the watershed. 

PMID- 24141129
TI  - Evaluating gulls as potential vehicles of Salmonella enterica serotype Newport
      (JJPX01.0061) contamination of tomatoes grown on the eastern shore of Virginia.
AB  - Salmonella enterica serovar Newport pattern JJPX01.0061 has been identified as
      causing several multistate outbreaks in the last 10 years, primarily due to
      contamination of tomatoes grown in Virginia. The goal of this study was to
      evaluate gulls as a potential vehicle of S. Newport pattern 61 contamination for
      tomatoes grown on the Eastern Shore of Virginia. Gull fecal samples were
      collected at four sites in eastern Virginia for 3 months (May to July) in 2012,
      resulting in 360 samples, among which Salmonella was isolated from 62 samples.
      Twenty-two serotypes and 26 pulsed-field gel electrophoresis DNA fingerprint
      patterns, including S. Newport pattern 61, were identified. All of the patterns
      that were isolated multiple times, with the exception of S. Newport patterns
      JJPX01.0030 and JJPX01.0061, were clustered in time and geographical location.
      These results strongly suggest that both patterns of S. Newport are endemic to
      sites on the Eastern Shore where gulls were sampled. This study provides
      additional information regarding the epidemiology of S. Newport pattern 61 in
      Virginia and how tomatoes sold interstate may become contaminated in the field. 

PMID- 24141130
TI  - Decay of fecal indicator bacterial populations and bovine-associated source
      tracking markers in freshly deposited cow pats.
AB  - Understanding the survival of fecal indicator bacteria (FIB) and microbial source
      tracking (MST) markers is critical to developing pathogen fate and transport
      models. Although pathogen survival in water microcosms and manure-amended soils
      is well documented, little is known about their survival in intact cow pats
      deposited on pastures. We conducted a study to determine decay rates of fecal
      indicator bacteria (Escherichia coli and enterococci) and bovine-associated MST
      markers (CowM3, Rum-2-bac, and GenBac) in 18 freshly deposited cattle feces from
      three farms in northern Georgia. Samples were randomly assigned to shaded or
      unshaded treatment in order to determine the effects of sunlight, moisture, and
      temperature on decay rates. A general linear model (GLM) framework was used to
      determine decay rates. Shading significantly decreased the decay rate of the E.
      coli population (P < 0.0001), with a rate of -0.176 day(-1) for the shaded
      treatment and -0.297 day(-1) for the unshaded treatment. Shading had no
      significant effect on decay rates of enterococci, CowM3, Rum-2-bac, and GenBac (P
      > 0.05). In addition, E. coli populations showed a significant growth rate (0.881
      day(-1)) in the unshaded samples during the first 5 days after deposition. UV-B
      was the most important parameter explaining the decay rate of E. coli
      populations. A comparison of the decay behaviors among all markers indicated that
      enterococcus concentrations exhibit a better correlation with the MST markers
      than E. coli concentrations. Our results indicate that bovine-associated MST
      markers can survive in cow pats for at least 1 month after excretion, and
      although their decay dynamic differs from the decay dynamic of E. coli
      populations, they seem to be reliable markers to use in combination with
      enterococci to monitor fecal pollution from pasture lands. 

PMID- 24141131
TI  - Estimating the prevalence of potential enteropathogenic Escherichia coli and
      intimin gene diversity in a human community by monitoring sanitary sewage.
AB  - Presently, the understanding of bacterial enteric diseases in the community and
      their virulence factors relies almost exclusively on clinical disease reporting
      and examination of clinical pathogen isolates. This study aimed to investigate
      the feasibility of an alternative approach that monitors potential
      enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC)
      prevalence and intimin gene (eae) diversity in a community by directly
      quantifying and characterizing target virulence genes in the sanitary sewage. The
      quantitative PCR (qPCR) quantification of the eae, stx1, and stx2 genes in
      sanitary sewage samples collected over a 13-month period detected eae in all 13
      monthly sewage samples at significantly higher abundance (93 to 7,240 calibrator
      cell equivalents [CCE]/100 ml) than stx1 and stx2, which were detected
      sporadically. The prevalence level of potential EPEC in the sanitary sewage was
      estimated by calculating the ratio of eae to uidA, which averaged 1.0% (sigma =
      0.4%) over the 13-month period. Cloning and sequencing of the eae gene directly
      from the sewage samples covered the majority of the eae diversity in the sewage
      and detected 17 unique eae alleles belonging to 14 subtypes. Among them, eae
      beta2 was identified to be the most prevalent subtype in the sewage, with the
      highest detection frequency in the clone libraries (41.2%) and within the
      different sampling months (85.7%). Additionally, sewage and environmental E. coli
      isolates were also obtained and used to determine the detection frequencies of
      the virulence genes as well as eae genetic diversity for comparison. 

PMID- 24141132
TI  - Microbial biotransformation of gentiopicroside by the endophytic fungus
      Penicillium crustosum 2T01Y01.
AB  - Endophytic fungi are symbiotic with plants and possess multienzyme systems
      showing promising metabolite potency with region selectivity and
      stereoselectivity. The aim of this study was to use these special microorganisms
      as an in vitro model to mimic the potential mammalian metabolites of a natural
      iridoid gentiopicroside (GPS, compound 1). The fungi isolated from a medicinal
      plant, Dendrobium candidum Wall. ex Lindl., were screened for their
      biotransformation abilities with GPS as the substrate, and one strain with high
      converting potency was identified as Penicillium crustosum 2T01Y01 on the basis
      of the sequence of the internal transcribed spacer of the ribosomal DNA region.
      Upon the optimized incubation of P. crustosum 2T01Y01 with the substrate, seven
      deglycosylated metabolites were detected by ultraperformance liquid
      chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS).
      Preparative-scale biotransformation with whole cells of the endophytic fungus
      resulted in the production of five metabolites, including three novel ones,
      5alpha-(hydroxymethyl)-6beta-methyl-3,4,5,6-tetrahydropyrano[3,4-c]pyran-1(8H)
      one (compound 2), (Z)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound
      3), and (E)-4-(1-hydroxybut-3-en-2-yl)-5,6-dihydropyran-2-one (compound 4), along
      with two known ones, 5alpha-(hydroxymethyl)-6beta-methyl-1H,3H-5,6
      dihydropyrano[3,4-c]pyran-1(3H)-one (compound 5) and 5alpha-(hydroxymethyl)
      6alpha-methyl-5,6-dihydropyrano[3,4-c]pyran-1(3H)-one (compound 6), aided by
      nuclear magnetic resonance and high-resolution mass spectral analyses. The other
      two metabolites were tentatively identified by online UPLC/Q-TOF MS as 5
      hydroxymethyl-5,6-dihydroisochromen-1-one (compound 7) and 5-hydroxymethyl
      3,4,5,6-tetrahydroisochromen-1-one (compound 8), and compound 8 is a new
      metabolite. To test the metabolic mechanism, the beta-glucosidase activity of the
      fungus P. crustosum 2T01Y01 was assayed with rho-nitrophenyl-beta-d
      glucopyranoside as a probe substrate, and the pathway of GPS biotransformation by
      strain 2T01Y01 is proposed. In addition, the hepatoprotective activities of GPS
      and metabolite compounds 2, 5, and 6 against human hepatocyte line HL-7702 injury
      induced by hydrogen peroxide were evaluated. 

PMID- 24141133
TI  - Extracellular electron transport-mediated Fe(III) reduction by a community of
      alkaliphilic bacteria that use flavins as electron shuttles.
AB  - The biochemical and molecular mechanisms used by alkaliphilic bacterial
      communities to reduce metals in the environment are currently unknown. We
      demonstrate that an alkaliphilic (pH > 9) consortium dominated by Tissierella,
      Clostridium, and Alkaliphilus spp. is capable of using iron (Fe(3+)) as a final
      electron acceptor under anaerobic conditions. Iron reduction is associated with
      the production of a freely diffusible species that, upon rudimentary purification
      and subsequent spectroscopic, high-performance liquid chromatography, and
      electrochemical analysis, has been identified as a flavin species displaying
      properties indistinguishable from those of riboflavin. Due to the link between
      iron reduction and the onset of flavin production, it is likely that riboflavin
      has an import role in extracellular metal reduction by this alkaliphilic
      community. 

PMID- 24141135
TI  - Cloning, expression and optimized production in a bioreactor of bovine chymosin B
      in Pichia (Komagataella) pastoris under AOX1 promoter.
AB  - The codon sequence optimized bovine prochymosin B gene was cloned under the
      control of the alcohol oxidase 1 promoter (AOX1) in the vector pPIC9K and
      integrated into the genome of the methylotrophic yeast Pichia (Komagataella)
      pastoris (P. pastoris) strain GS115. A transformant clone that showed resistance
      to over 4 mg G418/ml and displayed the highest milk-clotting activity was
      selected. Cell growth and recombinant bovine chymosin production were optimized
      in flask cultures during methanol induction phase achieving the highest coagulant
      activity with low pH values, a temperature of 25 degrees C and with the addition
      of sorbitol and ascorbic acid at the beginning of this period. The scaling up of
      the fermentation process to lab-scale stirred bioreactor using optimized
      conditions, allowed to reach 240 g DCW/L of biomass level and 96 IMCU/ml of milk
      clotting activity. The enzyme activity corresponded to 53 mg/L of recombinant
      bovine chymosin production after 120 h of methanol induction. Western blot
      analysis of the culture supernatant showed that recombinant chymosin did not
      suffer degradation during the protein production phase. By a procedure that
      included high performance gel filtration chromatography and 3 kDa fast
      ultrafiltration, the recombinant bovine chymosin was purified and concentrated
      from fermentation cultures, generating a specific activity of 800 IMCU/Total
      Abs(280 nm) and a total activity recovery of 56%. This study indicated that P.
      pastoris is a suitable expression system for bioreactor based fed-batch
      fermentation process for the efficient production of recombinant bovine chymosin
      under methanol-inducible AOX1 promoter.

PMID- 24141134
TI  - Impact of substratum surface on microbial community structure and treatment
      performance in biological aerated filters.
AB  - The impact of substratum surface property change on biofilm community structure
      was investigated using laboratory biological aerated filter (BAF) reactors and
      molecular microbial community analysis. Two substratum surfaces that differed in
      surface properties were created via surface coating and used to develop biofilms
      in test (modified surface) and control (original surface) BAF reactors. Microbial
      community analysis by 16S rRNA gene-based PCR-denaturing gradient gel
      electrophoresis (DGGE) showed that the surface property change consistently
      resulted in distinct profiles of microbial populations during replicate reactor
      start-ups. Pyrosequencing of the bar-coded 16S rRNA gene amplicons surveyed more
      than 90% of the microbial diversity in the microbial communities and identified
      72 unique bacterial species within 19 bacterial orders. Among the 19 orders of
      bacteria detected, Burkholderiales and Rhodocyclales of the Betaproteobacteria
      class were numerically dominant and accounted for 90.5 to 97.4% of the sequence
      reads, and their relative abundances in the test and control BAF reactors were
      different in consistent patterns during the two reactor start-ups. Three of the
      five dominant bacterial species also showed consistent relative abundance changes
      between the test and control BAF reactors. The different biofilm microbial
      communities led to different treatment efficiencies, with consistently higher
      total organic carbon (TOC) removal in the test reactor than in the control
      reactor. Further understanding of how surface properties affect biofilm microbial
      communities and functional performance would enable the rational design of new
      generations of substrata for the improvement of biofilm-based biological
      treatment processes. 

PMID- 24141136
TI  - Phosphoproteomics in drug discovery.
AB  - Several important aspects of the drug discovery process, including target
      identification, mechanism of action determination and biomarker identification as
      well as drug repositioning, require complete understanding of the effects of
      drugs on protein phosphorylation in relevant biological systems. Novel high
      throughput phosphoproteomic technologies can be employed to measure these
      phosphorylation events. In this review, we describe the advantages and
      limitations of state-of-the-art phosphoproteomic approaches such as mass
      spectrometry and antibody-based technologies in terms of sample and data
      throughput as well as data quality. We then discuss how datasets from each
      technology can be analyzed and how the results can be and have been applied to
      advance different aspects of the drug discovery process. 

PMID- 24141137
TI  - A simplified and efficient germline-specific CRISPR/Cas9 system for Drosophila
      genomic engineering.
AB  - The type II CRISPR/Cas9 system (clustered regularly interspaced short palindromic
      repeats/CRISPR-associated) has recently emerged as an efficient and simple tool
      for site-specific engineering of eukaryotic genomes. To improve its applications
      in Drosophila genome engineering, we simplified the standard two-component
      CRISPR/Cas9 system by generating a stable transgenic fly line expressing the Cas9
      endonuclease in the germline (Vasa-Cas9 line). By injecting vectors expressing
      engineered target-specific guide RNAs into Vasa-Cas9 fly embryos, mutations were
      generated from site-specific DNA cleavages and efficiently transmitted into
      progenies. Because Cas9 endonuclease is the universal component of the type II
      CRISPR/Cas9 system, site-specific genomic engineering based on this improved
      platform can be achieved with lower complexity and toxicity, greater consistency,
      and excellent versatility. 

PMID- 24141138
TI  - The role of mitochondrial electron transport in tumorigenesis and metastasis.
AB  - BACKGROUND: Tumor formation and spread via the circulatory and lymphatic drainage
      systems is associated with metabolic reprogramming that often includes increased
      glycolytic metabolism relative to mitochondrial energy production. However, cells
      within a tumor are not identical due to genetic change, clonal evolution and
      layers of epigenetic reprogramming. In addition, cell hierarchy impinges on
      metabolic status while tumor cell phenotype and metabolic status will be
      influenced by the local microenvironment including stromal cells, developing
      blood and lymphatic vessels and innate and adaptive immune cells. Mitochondrial
      mutations and changes in mitochondrial electron transport contribute to metabolic
      remodeling in cancer in ways that are poorly understood. SCOPE OF REVIEW: This
      review concerns the role of mitochondria, mitochondrial mutations and
      mitochondrial electron transport function in tumorigenesis and metastasis. MAJOR
      CONCLUSIONS: It is concluded that mitochondrial electron transport is required
      for tumor initiation, growth and metastasis. Nevertheless, defects in
      mitochondrial electron transport that compromise mitochondrial energy metabolism
      can contribute to tumor formation and spread. These apparently contradictory
      phenomena can be reconciled by cells in individual tumors in a particular
      environment adapting dynamically to optimally balance mitochondrial genome
      changes and bioenergetic status. GENERAL SIGNIFICANCE: Tumors are complex
      evolving biological systems characterized by genetic and adaptive epigenetic
      changes. Understanding the complexity of these changes in terms of bioenergetics
      and metabolic changes will permit the development of better combination
      anticancer therapies. This article is part of a Special Issue entitled Frontiers
      of Mitochondrial Research.

PMID- 24141139
TI  - Aquaporins and membrane diffusion of CO2 in living organisms.
AB  - BACKGROUND: Determination of CO2 diffusion rates in living cells revealed
      inconsistencies with existing models about the mechanisms of membrane gas
      transport. Mainly, these discrepancies exist in the determined CO2 diffusion
      rates of bio-membranes, which were orders of magnitudes below those for pure
      lipid bilayers or theoretical considerations as well as in the observation that
      membrane insertion of specific aquaporins was rescuing high CO2 transport rates.
      This effect was confirmed by functional aquaporin protein analysis in
      heterologous expression systems as well as in bacteria, plants and partly in
      mammals. SCOPE OF REVIEW: This review summarizes the arguments in favor of and
      against aquaporin facilitated membrane diffusion of CO2 and reports about its
      importance for the physiology of living organisms. MAJOR CONCLUSIONS: Most
      likely, the aquaporin tetramer forming an additional fifth pore is required for
      CO2 diffusion facilitation. Aquaporin tetramer formation, membrane integration
      and disintegration could provide a mechanism for regulation of cellular CO2
      exchange. The physiological importance of aquaporin mediated CO2 membrane
      diffusion could be shown for plants and cyanobacteria and partly for mammals.
      GENERAL SIGNIFICANCE: Taking the mentioned results into account, consequences for
      our current picture of cell membrane transport emerge. It appears that in some or
      many instances, membranes might not be as permeable as it was suggested by
      current bio-membrane models, opening an additional way of controlling the
      cellular influx or efflux of volatile substances like CO2. This article is part
      of a Special Issue entitled Aquaporins.

PMID- 24141141
TI  - Wake up to floppy eyelid syndrome.

PMID- 24141142
TI  - Immunotherapy for corneal inflammatory disorders: stepping up and down the
      ladder.

PMID- 24141140
TI  - Anti-inflammatory action of lipid nanocarrier-delivered myriocin: therapeutic
      potential in cystic fibrosis.
AB  - BACKGROUND: Sphingolipids take part in immune response and can initiate and/or
      sustain inflammation. Various inflammatory diseases have been associated with
      increased ceramide content, and pharmacological reduction of ceramide diminishes
      inflammation damage in vivo. Inflammation and susceptibility to microbial
      infection are two elements in a vicious circle. Recently, sphingolipid metabolism
      inhibitors were used to reduce infection. Cystic fibrosis (CF) is characterized
      by a hyper-inflammation and an excessive innate immune response, which fails to
      evolve into adaptive immunity and to eradicate infection. Chronic infections
      result in lung damage and patient morbidity. Notably, ceramide content in mucosa
      airways is higher in CF mouse models and in patients than in control mice or
      healthy subjects. METHODS: The therapeutic potential of myriocin, an inhibitor of
      the sphingolipid de novo synthesis rate limiting enzyme (Serine Palmitoyl
      Transferase, SPT),was investigated in CF cells and mice models. RESULTS: We
      treated CF human respiratory epithelial cells with myriocin, This treatment
      resulted in reduced basal, as well as TNFalpha-stimulated, inflammation. In turn,
      TNFalpha induced an increase in SPT in these cells, linking de novo synthesis of
      ceramide to inflammation. Furthermore, myriocin-loaded nanocarrier, injected
      intratrachea prior to P. aeruginosa challenge, enabled a significant reduction of
      lung infection and reduced inflammation. CONCLUSIONS: The presented data suggest
      that de novo ceramide synthesis is constitutively enhanced in CF mucosa and that
      it can be envisaged as pharmacological target for modulating inflammation and
      restoring effective innate immunity against acute infection. GENERAL
      SIGNIFICANCE: Myriocin stands as a powerful immunomodulatory agent for
      inflammatory and infectious diseases.

PMID- 24141143
TI  - Authors' response: central toxic keratopathy: a clinical case series.

PMID- 24141144
TI  - In silico prediction of the cell proliferation in porous scaffold using model of
      effective pore.
AB  - The mathematical prediction of cell proliferation in porous scaffold still
      remains a challenge. The analysis of existing models and experimental data
      confirms a need for a new solution, which takes into account cells" development
      on the scaffold pore walls as well as some additional parameters such as the pore
      size, cell density in cellular layers, the thickness of the growing cell layer
      and others. The simulations, presented below, are based on three main approaches.
      The first approach takes into account multilayer cell growth on the pore walls of
      the scaffold. The second approach is a simulation of cell proliferation in a
      discrete process as a continuous one. The third one is the representation of
      scaffold structure as a system of cylindrical channels. Oxygen (nutrient) mass
      transfer is realized inside these channels. The model, described below, proposes
      the new solution to time dependent description of cell proliferation in porous
      scaffold and optimized trophical conditions for tissue development. 

PMID- 24141145
TI  - Improving feature size uniformity from interference lithography systems with non
      uniform intensity profiles.
AB  - The non-uniform intensity profile of Gaussian-like laser beams used in
      interference lithography (IL) leads to a non-uniform dose and feature size
      distribution across the sample. Previously described methods to improve dose
      uniformity are reviewed. However, here we examine the behavior of the non
      uniformity from the viewpoint of photoresist response rather than the IL system
      configuration. Samples with a fixed intra-sample dose profile were exposed with
      an increasing average dose. A line/space pattern with a period of 240 nm across
      an area of 2 * 2 cm(2) was produced using IL on identical samples using a HeCd
      laser operated at 325 nm and a Lloyd's mirror IL system. A binary model of
      photoresist response predicts that the absolute range of line widths in
      nanometers should be significantly reduced as the overall sample dose is
      increased. We have experimentally verified a reduction in the range of line
      widths within a given sample from 50 to 16 nm as the overall dose is increased by
      only 60%. This resulted in a drop in the narrowest line width from 120 to 65 nm.
      An etch process is demonstrated to increase the line width by generating a wider
      secondary chrome hard mask from the narrowly patterned primary chrome hard mask.
      The subsequent fabrication of a silicon nanoimprint mold is used as a
      demonstration of the technique. 

PMID- 24141146
TI  - Achalasia.

PMID- 24141147
TI  - Modification of the sampling algorithm for reverse Monte Carlo modeling with an
      insufficient data set.
AB  - A new sampling method for reverse Monte Carlo (RMC) modeling has been developed
      to constitute a reasonable structural model with insufficient experimental data.
      Another merit of this method is its very low computational cost because the
      algorithm uses only the three nearest atomic coordinations in moving a selected
      atom. In order to test the method, RMC modeling with this algorithm was carried
      out for the scattering data of NaCl melts. The partial pair distribution
      functions obtained by the RMC modeling had no spikes or atomic aggregation in the
      cutoff distance region and agreed well with experimental data. 

PMID- 24141148
TI  - C57BL/6J congenic Prp-TDP43A315T mice develop progressive neurodegeneration in
      the myenteric plexus of the colon without exhibiting key features of ALS.
AB  - ALS therapy development has been hindered by the lack of rodent animal models.
      The discovery of TDP-43, a transcription factor that accumulates in the cytoplasm
      of motor neurons (MNs) in most cases of ALS, prompted attempts to develop TDP-43
      based models of the disease. The current study sought to examine, in extensive
      detail, the emerging disease phenotype of a transgenic mouse model that
      overexpresses a mutant human TDP-43 (hTDP-43) gene under mouse prion promoter
      control. Careful attention was given to ALS-like characteristics to determine the
      appropriateness of this model for testing therapies for ALS. In light of previous
      reports that gastrointestinal (GI) dysfunction is responsible for early death in
      these mice, gut immunohistochemistry (IHC) and longitudinal gut motility assays
      were used to identify the onset and the progression of these defects. IHC studies
      revealed that site-specific overexpression of the hTDP-43 transgene in colonic
      myenteric plexes resulted in progressive neurodegeneration in this region. This
      change was associated with progressively reduced GI motility, culminating in
      frank stasis that was primarily responsible for decreasing longevity in these
      mice. The disease phenotype was gender- and genetic background-dependent, with
      congenic C57BL/6J male mice exhibiting the most aggressive form of the disease.
      Spinal cord IHC revealed ubiquitin-positive inclusions, but not TDP-43
      aggregates, in the cytoplasm of MNs. Neither gender exhibited compelling ALS-like
      neuromuscular deficits, irrespective of age. While this model may be useful for
      studying GI tract neurodegeneration, in its present state it does not display a
      phenotype suitable for testing ALS therapeutics.

PMID- 24141150
TI  - AHVLA seeks views on its plans to reform OV training and assessment.

PMID- 24141149
TI  - GABAA receptors are located in cholinergic terminals in the nucleus pontis oralis
      of the rat: implications for REM sleep control.
AB  - The oral pontine reticular formation (PnO) of rat is one region identified in the
      brainstem as a rapid eye movement (REM) sleep induction zone. Microinjection of
      GABA(A) receptor antagonists into PnO induces a long lasting increase in REM
      sleep, which is similar to that produced by cholinergic agonists. We previously
      showed that this REM sleep-induction can be completely blocked by a muscarinic
      antagonist, indicating that the REM sleep-inducing effect of GABA(A) receptor
      antagonism is dependent upon the local cholinergic system. Consistent with these
      findings, it has been reported that GABA(A) receptor antagonists microdialyzed
      into PnO resulted in increased levels of acetylcholine. We hypothesize that
      GABA(A) receptors located on cholinergic boutons in the PnO are responsible for
      the REM sleep induction by GABA(A) receptor antagonists through blocking GABA
      inhibition of acetylcholine release. Cholinergic, varicose axon fibers were
      studied in the PnO by immunofluorescence and confocal, laser scanning microscopy.
      Immunoreactive cholinergic boutons were found to be colocalized with GABA(A)
      receptor subunit protein gamma2. This finding implicates a specific subtype and
      location of GABA(A) receptors in PnO of rat in the control of REM sleep.

PMID- 24141151
TI  - Defra issues draft advice on enforcing antisocial behaviour measures.

PMID- 24141152
TI  - BVA President calls for vets to be at the heart of food supply chain initiatives.

PMID- 24141153
TI  - European reform of pig meat inspections to go ahead.

PMID- 24141155
TI  - Pilot badger culls to be extended.

PMID- 24141157
TI  - Prescribing, dispensing and welfare.

PMID- 24141159
TI  - Vet suspended from the Register for falsifying clinical records.

PMID- 24141160
TI  - Science and networking at AVTRW meeting in Ireland.

PMID- 24141161
TI  - ECAT-V: where clinical and research training meet.

PMID- 24141162
TI  - Selecting the right students.

PMID- 24141164
TI  - Marek's disease in commercial turkey flocks.

PMID- 24141165
TI  - Mycobacterium bovis in an Egyptian mongoose.

PMID- 24141166
TI  - Closure of the Mid-West Veterinary Association.

PMID- 24141167
TI  - Veterinary Benevolent Fund bungalows.

PMID- 24141168
TI  - Survey on the recognition and management of pain in cattle.

PMID- 24141169
TI  - Selective activation of lectin-like oxidized low-density lipoprotein receptor-1
      mediates C-reactive protein-evoked endothelial vasodilator dysfunction in
      coronary arterioles.
AB  - RATIONALE: Studies in cultured endothelium implicate that lectin-like oxidized
      low-density lipoprotein receptor-1 (LOX-1) or Fcgamma receptor II (CD32)
      contributes to the proatherogenic effects of C-reactive protein (CRP). However,
      the identity of the receptors linking to deleterious actions of CRP in vasomotor
      regulation remains unknown. OBJECTIVE: We tested the hypothesis that LOX-1
      contributes to adverse effects of CRP on endothelium-dependent vasomotor function
      in resistance arterioles. METHODS AND RESULTS: Porcine coronary arterioles were
      isolated for vasoreactivity study, dihydroethidium fluorescence staining of
      superoxide, immunohistochemical localization of receptors, immunoprecipitation of
      receptor/CRP interaction, and protein blot. Intraluminal treatment of pressurized
      arterioles with a pathophysiological level of CRP (7 ug/mL; 60 minutes)
      attenuated endothelium-dependent nitric oxide-mediated and prostacyclin-mediated
      dilations to serotonin and arachidonic acid, respectively. LOX-1 and CD32 were
      detected in the endothelium of arterioles. Blockade of LOX-1 with either
      pharmacological antagonist kappa-carrageenan or anti-LOX-1 antibody prevented the
      detrimental effect of CRP on vasodilator function, whereas anti-CD32 antibody
      treatment was ineffective. Denudation of endothelium and blockade of LOX-1 but
      not CD32 prevented CRP-induced elevation of superoxide in the vessel wall. CRP
      was coimmunoprecipitated with LOX-1 and CD32 from CRP-treated arterioles.
      Similarly, LOX-1 and CD32 blockade prevented CRP-induced arteriolar expression of
      plasminogen activator inhibitor-1, a thrombogenic protein. CONCLUSIONS: CRP
      elicits endothelium-dependent oxidative stress and compromises nitric oxide
      mediated and prostacyclin-mediated vasomotor function via LOX-1 activation. In
      contrast, both LOX-1 and CD32 mediate plasminogen activator inhibitor-1
      upregulation in arterioles by CRP. Thus, activation of LOX-1 and CD32 may
      contribute to vasomotor dysfunction and proatherogenic actions of CRP,
      respectively.

PMID- 24141170
TI  - Dynamic release and clearance of circulating microparticles during cardiac
      stress.
AB  - RATIONALE: Microparticles are cell-derived membrane vesicles, relevant to a range
      of biological responses and known to be elevated in cardiovascular disease.
      OBJECTIVE: To investigate microparticle release during cardiac stress and how
      this response differs in those with vascular disease. METHODS AND RESULTS: We
      measured a comprehensive panel of circulating cell-derived microparticles by a
      standardized flow cytometric protocol in 119 patients referred for stress
      echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not
      leukocyte, granulocyte, or monocyte-derived microparticles were elevated
      immediately after a standardized dobutamine stress echocardiogram and decreased
      after 1 hour. Twenty-five patients developed stress-induced wall motion
      abnormalities suggestive of myocardial ischemia. They had similar baseline
      microparticle levels to those who did not develop ischemia, but, interestingly,
      their microparticle levels did not change during stress. Furthermore, no stress
      induced increase was observed in those without inducible ischemia but with a
      history of vascular disease. Fourteen patients subsequently underwent coronary
      angiography. A microparticle rise during stress echocardiography had occurred
      only in those with normal coronary arteries. CONCLUSIONS: Procoagulant, platelet,
      erythrocyte, and endothelial microparticles are released during cardiac stress
      and then clear from the circulation during the next hour. This stress-induced
      rise seems to be a normal physiological response that is diminished in those with
      vascular disease.

PMID- 24141172
TI  - Lauroyl-L-aspartate decreased food intake and body temperature in neonatal
      chicks.
AB  - We hypothesized that the effects of L- and D-amino acids might be influenced when
      conjugated with fatty acid. Thus, the effects of oral administration of lauroyl-L
      aspartate (Lau-L-Asp) as well as lauroyl-D-aspartate (Lau-D-Asp) were examined.
      In Experiment 1, oral administration of both Lau-L-Asp and Lau-D-Asp decreased
      food intake while L- or D-Asp did not influence food intake. Interestingly, only
      Lau-L-Asp decreased body temperature. Experiment 2 was conducted to determine
      whether non-conjugated mixture of L-Asp plus lauric acid has same effects under
      ad libitum feeding conditions. Lau-L-Asp decreased food intake and body
      temperature, but L-Asp plus lauric acid did not show any effect studied. In
      Experiment 3, we found that Lau-L-Asp declined food intake as well as time
      dependently suppressed the body temperature in fasted chicks. However, L-Asp plus
      lauric acid did not show any effect. These results suggest that Lau-L-Asp may
      exert anorexigenic and hypothermic actions in chicks.

PMID- 24141173
TI  - Delayed administration of zingerone mitigates the behavioral and histological
      alteration via repression of oxidative stress and intrinsic programmed cell death
      in focal transient ischemic rats.
AB  - The neuronal mitochondria succumb to ischemia-reperfusion injury and release huge
      amount of reactive oxygen species and ultimately lead the neurons to intrinsic
      pathway of programmed cell death (iPCD). The present study was undertaken to
      elucidate the ischemia-reperfusion-induced oxidative stress and molecular events
      in iPCD 24 h post ischemia-reperfusion injury and plausible mitigation by
      zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral
      artery was occluded for 2 h followed by reperfusion for 22 hours. A maximum
      infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle
      cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and
      100 mg/kg b.wt. orally twice) at 5 h and 12 h from initiation of MCAO showed a
      significant reduction in infarct volume and mitochondrial injury (p<0.001).
      Zingerone treatment significantly improved behavioral outputs (p<0.05) and
      histological architecture (p<0.001) by reducing lipid peroxidation (p<0.01),
      augmenting the reduced glutathione content (p<0.01) and restoring Na(+)-K(+)
      ATPase and superoxide dismutase activities (p<0.01) in MCAO brain. Zingerone
      successfully reduced the caspase-3 and -9 activities in MCAO group (p<0.05) and
      succeeded in lowering the expressions of pro-apoptotic proteins - Apaf-1 and Bax
      (p<0.001). The present study suggests that zingerone is a potent antioxidant that
      salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative
      stress.

PMID- 24141174
TI  - Appropriate use of special stains for identifying Helicobacter pylori:
      Recommendations from the Rodger C. Haggitt Gastrointestinal Pathology Society.
AB  - Helicobacter pylori is a major cause of gastroduodenal injury, gastric cancer,
      and lymphoma, and, thus, there is great interest in its detection and
      eradication. Several detection methods are available, including histochemical and
      immunohistochemical stains. Application of these stains in clinical practice is
      heterogenous, to say the least. Although they were developed to enhance H. pylori
      detection, changing practice models, financial considerations, and a perceived
      need for rapid case turnaround have led to their widespread use in routine
      staining studies ordered reflexively on all gastric biopsies. Emerging data
      suggest that most of these stains are not needed to establish a diagnosis of H.
      pylori infection, and their added value when biopsies show minimal, or no,
      inflammation is not clear. In this manuscript, the Rodger C. Haggitt
      Gastrointestinal Pathology Society puts forth recommendations regarding ancillary
      stain usage for H. pylori detection based upon critical literature review and
      collective experience. Pathologists rarely, if ever, detect H. pylori in "normal"
      biopsies, but readily observe them in optimally stained hematoxylin and eosin
      sections from infected patients. Therefore, we suggest that use of ancillary
      stains is appropriate when biopsies show chronic, or chronic active, gastritis
      without detectable H. pylori in hematoxylin and eosin-stained sections, but
      performing them "up front" on all gastric biopsies is generally unnecessary.
      Application of these stains to nongastric biopsies and polyps is appropriate in
      an extremely limited set of circumstances. It is our hope that recommendations
      provided herein will provide helpful information to gastroenterologists,
      pathologists, and others involved in the evaluation of patients for possible H.
      pylori infection.

PMID- 24141175
TI  - Hypertension prevalence and control in Romania at a seven-year interval.
      Comparison of SEPHAR I and II surveys.
AB  - OBJECTIVES: To present the current epidemiologic situation regarding
      hypertension's prevalence and control in Romania's adult population (revealed by
      SEPHAR II survey results) and to evaluate their tendency during the last 7 years
      (by comparing with the SEPHAR I survey results). METHODS: The two SEPHAR cross
      sectional national surveys were conducted on a representative sample for the
      Romanian adult population (SEPHAR I: 2017 individuals aged 18-85 years, 45%
      response rate, SEPHAR II: 1975 individuals aged 18-80 years, 69% response rate),
      by means of questionnaire interview, blood pressure (BP) and anthropometric
      measurements during two study visits. Hypertension was defined as SBP at least
      140  mmHg and/or DBP at least 90  mmHg at both study visits or previously
      diagnosed hypertension under current treatment. Controlled BP was defined as SBP
      less than 140  mmHg and DBP less than 90  mmHg in currently treated hypertensive
      individuals. RESULTS: Prevalence of hypertension in Romanian is 40.41%, awareness
      of hypertension is 69.55%, with 59.15% hypertensive individuals under current
      treatment with a control rate of 25%. In the last 7 years, there has been a 10.7%
      decrease in hypertension's prevalence together with an increase by 57% in
      awareness of hypertension and an increase by 52% in treatment of hypertension,
      leading to almost doubling of the hypertension's control rate in all hypertensive
      individuals. CONCLUSION: Although in the last 7 years, the tendency of
      hypertension's prevalence seems to be a descending one with an increasing trend
      in awareness, treatment and control of this condition, hypertension in Romania at
      this time still remains an 'unsolved equation'.

PMID- 24141177
TI  - Enhanced supercapacitance in anodic TiO2 nanotube films by hydrogen plasma
      treatment.
AB  - One-dimensional anodic titanium oxide (ATO) nanotube arrays hold great potential
      as electrode materials for high-performance electrochemical supercapacitors.
      However, their poor electronic conductivity limits their practical applications.
      Here, we develop a hydrogen (H2) plasma treatment method to greatly improve the
      electrochemical performance of ATO electrodes. Compared with pristine ATO, the
      nanotubes treated by H2 plasma illumination (ATO-H) present a rough and amorphous
      layer at the surface of the nanotubes with simultaneously incorporated Ti(3+) and
      -OH groups. At a current density of 0.05 mA cm(-2) in charge-discharge
      measurements, the specific capacitance of the ATO-H electrode has substantially
      increased ~7.4 times, with a value as high as 7.22 mF cm(-2). Moreover, the novel
      ATO-H electrode has also exhibited excellent rate capability (6.37 mF cm(-2) at a
      current density of 2 mA cm(-2)) and cycling performance with no degradation after
      10,000 cycles.

PMID- 24141176
TI  - Experiences in recruiting volunteers through community based initiatives in phase
      1 vaccine trials in India.
AB  - Success of HIV vaccine trials is dependent on infrastructural preparedness of the
      site, technical expertise of the trial team and strong Socio-political support of
      the local community. The processes followed and experiences gained while
      implementing various community based initiatives for recruitment of healthy
      volunteers during the three HIV vaccine trials in India are described. Major
      initiatives in community engagement implemented for the first time in India
      included establishment and involvement of Community Advisory Board and capacity
      building and engagement of lay community based volunteers called "peers" using
      "lay health promotion" model. Community education program designed for trial
      participants' education, identification and enrollment was a three-tiered
      approach, moving from large community awareness meetings (first step) to facility
      based small group meeting to provide trial specific information (second step);
      ending with one-to-one vaccine center based meeting with the volunteers to clear
      doubts, myths, and misconceptions about HIV/AIDS, the experimental vaccine and
      HIV vaccine trials as well as to explain trial specific procedures (third step).
      It is important to focus on gender issues, locally relevant socio-cultural
      factors, informed consent, and post-trial care related matters during the conduct
      of sensitive clinical trials in socio-culturally diverse and resource limited
      setting like India.

PMID- 24141178
TI  - Epigenetic memory of environmental organisms: a reflection of lifetime stressor
      exposures.
AB  - Both genetic and epigenetic responses of organisms to environmental factors,
      including chemical exposures, influence adaptation, susceptibility to toxicity
      and biodiversity. In model organisms, it is established that epigenetic
      alterations, including changes to the methylome, can create a memory of the
      received signal. This is partly evidenced through the analysis of epigenetic
      differences that develop between identical twins throughout their lifetime. The
      epigenetic marks induce alterations to the gene expression profile, which, in
      addition to mediating homeostatic responses, have the potential to promote an
      abnormal physiology either immediately or at a later stage of development, for
      example leading to an adult onset of disease. Although this has been well
      established, epigenetic mechanisms are not considered in chemical risk assessment
      or utilised in the monitoring of the exposure and effects of chemicals and
      environmental change. In this review, epigenetic factors, specifically DNA
      methylation, are highlighted as mechanisms of adaptation and response to
      environmental factors and which, if persistent, have the potential,
      retrospectively, to reflect previous stress exposures. Thus, it is proposed that
      epigenetic "foot-printing" of organisms could identify classes of chemical
      contaminants to which they have been exposed throughout their lifetime. In some
      cases, the potential for persistent transgenerational modification of the
      epigenome may also inform on parental germ cell exposures. It is recommended that
      epigenetic mechanisms, alongside genetic mechanisms, should eventually be
      considered in environmental toxicity safety assessments and in biomonitoring
      studies. This will assist in determining the mode of action of toxicants, no
      observed adverse effect level and identification of biomarkers of toxicity for
      early detection and risk assessment in toxicology but there are critical areas
      that remain to be explored before this can be achieved. 

PMID- 24141171
TI  - The neurobiology of alcohol consumption and alcoholism: an integrative history.
AB  - Studies of the neurobiological predisposition to consume alcohol (ethanol) and to
      transition to uncontrolled drinking behavior (alcoholism), as well as studies of
      the effects of alcohol on brain function, started a logarithmic growth phase
      after the repeal of the 18th Amendment to the United States Constitution.
      Although the early studies were primitive by current technological standards,
      they clearly demonstrated the effects of alcohol on brain structure and function,
      and by the end of the 20th century left little doubt that alcoholism is a
      "disease" of the brain. This review traces the history of developments in the
      understanding of ethanol's effects on the most prominent inhibitory and
      excitatory systems of brain (GABA and glutamate neurotransmission). This
      neurobiological information is integrated with knowledge of ethanol's actions on
      other neurotransmitter systems to produce an anatomical and functional map of
      ethanol's properties. Our intent is limited in scope, but is meant to provide
      context and integration of the actions of ethanol on the major neurobiologic
      systems which produce reinforcement for alcohol consumption and changes in brain
      chemistry that lead to addiction. The developmental history of neurobehavioral
      theories of the transition from alcohol drinking to alcohol addiction is
      presented and juxtaposed to the neurobiological findings. Depending on one's
      point of view, we may, at this point in history, know more, or less, than we
      think we know about the neurobiology of alcoholism. 

PMID- 24141179
TI  - Effects of chronic exercise and treatment with the antipsychotic drug olanzapine
      on hippocampal volume in adult female rats.
AB  - Numerous studies have reported that the hippocampus in schizophrenia patients is
      reduced in volume compared to the normal population. Antipsychotic medications
      have had mixed benefits in maintaining hippocampal volume or reversing volume
      loss. Recent evidence indicates that routine aerobic exercise represents a
      promising intervention for reversing hippocampal loss and cognitive deficits. In
      the present study, we measured the effects of chronic treatment with olanzapine
      and daily exercise on the hippocampal volumes of rats. Adult female rats were
      treated during the week with either olanzapine (10mg/kg) or vehicle for 9
      consecutive weeks. Subgroups of animals were provided access to exercise running
      wheels for 1 or 3h per day during the same period, or were sedentary. Metabolic
      indices, including glucose tolerance, were measured on a weekly basis. At the
      conclusion of the study, brains were perfused and hippocampal sections were Nissl
      stained. Total hippocampal volume was measured using the Cavalieri estimator.
      Treatment with olanzapine caused a significant decrease in hippocampal volume in
      sedentary rats. However, exercise was able to reverse most of this volume loss.
      The hippocampal sub-regions of the dentate gyrus and CA1 were most strongly
      affected by olanzapine and exercise. Of interest, there was a strong and highly
      significant negative correlation between glucose intolerance and hippocampal
      volume, whereby greater glucose intolerance was associated with a smaller
      hippocampal volume. These findings indicate that exercise may have beneficial
      effects on the hippocampus when antipsychotic medication can contribute to
      changes in volume. 

PMID- 24141180
TI  - Effects of voluntary exercise on hippocampal long-term potentiation in morphine
      dependent rats.
AB  - This study was designed to examine the effect of voluntary exercise on
      hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats
      were randomly distributed into the saline-sedentary (Sal/Sed), the dependent
      sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc)
      groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a
      running wheel for 10 days. The Sal/Sed and the morphine-sedentary groups were
      kept sedentary for the same extent of time. Morphine (10 mg/kg) was injected bi
      daily (12 h interval) during 10 days of voluntary exercise. On day 11, 2h after
      the morphine injection, the in vivo LTP in the dentate gyrus of the hippocampus
      was examined. The theta frequency primed bursts were delivered to the perforant
      path for induction of LTP. Population spike (PS) amplitude and the field
      excitatory post-synaptic potentials (fEPSP) slope were measured as indices of
      increase in synaptic efficacy. Chronic morphine increased the mean basal EPSP,
      and augmented PS-LTP. Exercise significantly increased the mean baseline EPSP and
      PS responses, and augmented PS-LTP in both saline and morphine-treated groups.
      Moreover, the increase of PS-LTP in the morphine-exercise group was greater
      (22.5%), but not statistically significant, than that of the Sal/Exc group. These
      results may imply an additive effect between exercise and morphine on mechanisms
      of synaptic plasticity. Such an interaction between exercise and chronic morphine
      may influence cognitive functions in opiate addicts.

PMID- 24141181
TI  - The role of Atg29 phosphorylation in PAS assembly.
AB  - Macroautophagy (hereafter autophagy) initiates at the phagophore assembly site
      (PAS), where most of the AuTophaGy-related (Atg) proteins are at least
      transiently localized. As the first protein complex targeted to the PAS, the
      Atg17-Atg31-Atg29 complex serves as the scaffold for other Atg proteins and plays
      a critical role for the organization of the PAS, and in autophagy initiation. We
      recently showed that this complex is constitutively formed and activated by the
      phosphorylation of Atg29 when autophagy is induced. Phosphorylation of Atg29 is
      required for its interaction with Atg11, another scaffold protein, and its
      function for promoting the proper assembly of the PAS. Single-particle electron
      microscopy analysis of the Atg17-Atg31-Atg29 complex reveals an elongated
      structure with Atg29 located at the opposing ends. This structural arrangement
      allows Atg29 to interact with Atg11, and is critical in the organization of the
      intact Atg1 complex. 

PMID- 24141183
TI  - 3D spatial resolution improvement by dual-axis electron tomography: application
      to tri-gate transistors.
AB  - The performance of semiconductor devices can be linked to geometry and variations
      of the structure. For transistors in particular, the geometry of the gate stack
      is essential. In this work we investigate the gate stack of a tri-gate transistor
      using dual-axis electron tomography. This allows the reconstruction of all
      surfaces of the gate of the transistor with high resolution and measurement of
      the local thickness of the gate oxide. While previously, dual-axis electron
      tomography was employed for reducing missing wedge artifacts, our work
      demonstrates the potential of dual-axis tomography for improving the resolution
      of a tomographic reconstruction, even for structures not affected by missing
      wedge artifacts. By simulations and experiments we show the value of dual-axis
      tomography for characterization of nanoscale devices as an approach that requires
      no prior information and that can be easily extended even to more than two tilt
      axes. 

PMID- 24141182
TI  - Cyclic AMP synergizes with butyrate in promoting beta-defensin 9 expression in
      chickens.
AB  - Host defense peptides (HDP) have both microbicidal and immunomodulatory
      properties. Specific induction of endogenous HDP synthesis has emerged as a novel
      approach to antimicrobial therapy. Cyclic adenosine monophosphate (cAMP) and
      butyrate have been implicated in HDP induction in humans. However, the role of
      cAMP signaling and the possible interactions between cAMP and butyrate in
      regulating HDP expression in other species remain unknown. Here we report that
      activation of cAMP signaling induces HDP gene expression in chickens as
      exemplified by beta-defensin 9 (AvBD9). We further showed that, albeit being weak
      inducers, cAMP agonists synergize strongly with butyrate or butyrate analogs in
      AvBD9 induction in macrophages and primary jejunal explants. Additionally, oral
      supplementation of forskolin, an adenylyl cyclase agonist in the form of a Coleus
      forskohlii extract, was found to induce AvBD9 expression in the crop of chickens.
      Furthermore, feeding with both forskolin and butyrate showed an obvious synergy
      in triggering AvBD9 expression in the crop and jejunum of chickens. Surprisingly,
      inhibition of the MEK-ERK mitogen-activated protein kinase (MAPK) pathway
      augmented the butyrate-FSK synergy, whereas blocking JNK or p38 MAPK pathway
      significantly diminished AvBD9 induction in chicken macrophages and jejunal
      explants in response to butyrate and FSK individually or in combination.
      Collectively, these results suggest the potential for concomitant use of butyrate
      and cAMP signaling activators in enhancing HDP expression, innate immunity, and
      disease resistance in both animals and humans. 

PMID- 24141184
TI  - Lentivirus-mediated ERK2 siRNA reduces joint capsule fibrosis in a rat model of
      post-traumatic joint contracture.
AB  - Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important
      role in the development of post-traumatic joint contractures. Using a rat injury
      model, we investigated whether treatment with ERK2 small interfering RNA (siRNA)
      could reduce the extent of joint capsule fibrosis after an induced injury. Rats
      were separated into three groups (n = 32 each): non-operated control group,
      operated contracture group and contracture-treatment group. Stable post-traumatic
      joint contracture was created through surgical intra-articular joint injury
      followed by eight weeks of immobilization. In the contracture-treatment group,
      the rats were treated with lentivirus (LV)-mediated ERK2 siRNA at days 3 and 7
      post-surgery. The posterior joint capsule was assessed by western blotting,
      immunohistochemistry and biochemical analysis for changes in ERK2, phosphorylated
      (p)-ERK2, myofibroblast, total collagen and relative collagen Type III expression
      level. Biomechanical testing was used to assess the development of flexion
      contractures. Statistical analysis was performed using an analysis of variance.
      In the operated contracture group, rats that developed flexion contractures also
      showed elevated phosphorylated p-ERK2 expression. In the contracture-treatment
      group, ERK2 siRNA significantly reduced p-ERK2 expression levels, as well as the
      severity of flexion contracture development (p < 0.01). Myofibroblast numbers and
      measurements of total collagen content were also significantly reduced following
      ERK2 siRNA (p < 0.01). Relative collagen type III expression as a proportion of
      total of Types I and III collagen, however, was significantly increased in
      response to ERK2 siRNA (p < 0.01). Our findings demonstrate a role for ERK2 in
      the induction of joint capsule fibrosis after injury. Furthermore, we show that
      development of flexion contractures and the resultant increase of joint capsule
      fibrosis can be reduced by LV-mediated ERK2 siRNA treatment. 

PMID- 24141186
TI  - Serial changes of serum growth factor levels and liver regeneration after partial
      hepatectomy in healthy humans.
AB  - This study aimed to investigate the associations of the serial changes of serum
      levels of various growth factors with liver regeneration after hepatectomy in
      healthy liver donors. Sixteen healthy liver donors who underwent conventional
      liver resection were included. Serum levels of various growth factors before
      hepatectomy and on postoperative day (POD) 1, 3, 5 and 7 were measured. Liver
      volume data calculated by multi-detector computed tomography using workstation.
      The ratio of remnant liver volume on POD 0 to liver volume before the operation
      was 51% +/- 20%. The ratio of liver volume on POD 14 to liver volume on POD 0
      were inversely correlated with remnant liver volume on POD 0 (r = -0.91). The
      ratio of liver volume on POD 14 to liver volume on POD 0 were significantly
      correlated with serum hepatocyte growth factor (HGF) levels on POD 1 (r = 0.54),
      serum leptin levels on POD 1 (r = 0.54), and serum macrophage colony-stimulating
      factor (M-CSF) levels on POD 5 (r = 0.76) and POD 7 (r = 0.80). These results
      suggest that early-phase elevation of serum levels of HGF, leptin and M-CSF may
      be associated with the acceleration of liver regeneration after hepatectomy in
      humans. 

PMID- 24141187
TI  - Boronic Acid-based approach for separation and immobilization of glycoproteins
      and its application in sensing.
AB  - Glycoproteins influence a broad spectrum of biological processes including cell
      cell interaction, host-pathogen interaction, or protection of proteins against
      proteolytic degradation. The analysis of their glyco-structures and concentration
      levels are increasingly important in diagnosis and proteomics. Boronic acids can
      covalently react with cis-diols in the oligosaccharide chains of glycoproteins to
      form five- or six-membered cyclic esters. Based on this interaction, boronic acid
      based ligands and materials have attracted much attention in both chemistry and
      biology as the recognition motif for enrichment and chemo/biosensing of
      glycoproteins in recent years. In this work, we reviewed the progress in the
      separation, immobilization and detection of glycoproteins with boronic acid
      functionalized materials and addressed its application in sensing. 

PMID- 24141188
TI  - Overexpression of ferredoxin, PETF, enhances tolerance to heat stress in
      Chlamydomonas reinhardtii.
AB  - Reactive oxygen species (ROS) produced by plants in adverse environments can
      cause damage to organelles and trigger cell death. Removal of excess ROS can be
      achieved through the ascorbate scavenger pathway to prevent plant cell death. The
      amount of this scavenger can be regulated by ferredoxin (FDX). Chloroplastic FDXs
      are electron transfer proteins that perform in distributing photosynthetic
      reducing power. In this study, we demonstrate that overexpression of the
      endogenous photosynthetic FDX gene, PETF, in Chlamydomonas reinhardtii could
      raise the level of reduced ascorbate and diminish H2O2 levels under normal growth
      conditions. Furthermore, the overexpressing PETF transgenic Chlamydomonas lines
      produced low levels of H2O2 and exhibited protective effects that were observed
      through decreased chlorophyll degradation and increased cell survival under heat
      stress conditions. The findings of this study suggest that overexpression of PETF
      can increase the efficiency of ROS scavenging in chloroplasts to confer heat
      tolerance. The roles of PETF in the downregulation of the ROS level offer a
      method for potentially improving the tolerance of crops against heat stress. 

PMID- 24141185
TI  - Protein glutathionylation in cardiovascular diseases.
AB  - The perturbation of thiol-disulfide homeostasis is an important consequence of
      many diseases, with redox signals implicated in several physio-pathological
      processes. A prevalent form of cysteine modification is the reversible formation
      of protein mixed disulfides with glutathione (S-glutathionylation). The abundance
      of glutathione in cells and the ready conversion of sulfenic acids to S
      glutathione mixed disulfides supports the reversible protein S-glutathionylation
      as a common feature of redox signal transduction, able to regulate the activities
      of several redox sensitive proteins. In particular, protein S-glutathionylation
      is emerging as a critical signaling mechanism in cardiovascular diseases, because
      it regulates numerous physiological processes involved in cardiovascular
      homeostasis, including myocyte contraction, oxidative phosphorylation, protein
      synthesis, vasodilation, glycolytic metabolism and response to insulin. Thus,
      perturbations in protein glutathionylation status may contribute to the etiology
      of many cardiovascular diseases, such as myocardial infarction, cardiac
      hypertrophy and atherosclerosis. Various reports show the importance of oxidative
      cysteine modifications in modulating cardiovascular function. In this review, we
      illustrate tools and strategies to monitor protein S-glutathionylation and
      describe the proteins so far identified as glutathionylated in myocardial
      contraction, hypertrophy and inflammation. 

PMID- 24141191
TI  - Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor
      engineered T cells.
AB  - Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells is a
      promising therapy for cancers. However, the safety of this approach is concerned.
      Cytokine release syndrome (CRS) is a common but lethal complication of CAR-T cell
      therapy. The development of CRS correlates with CAR structures, tumor type and
      burden, and patients' genetic polymorphisms. CRS related adverse events may be
      reduced by designing safer CARs and CAR-T cells and following strict dose
      escalation scheme. Timely and effective cytokine-directed treatment with
      corticosteroid and various cytokine antagonists is important to avoid CRS
      associated death. 

PMID- 24141192
TI  - Riboswitches in eubacteria sense the second messenger c-di-AMP.
AB  - Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial
      second messenger implicated in the control of cell wall metabolism, osmotic
      stress responses and sporulation. However, the mechanisms by which c-di-AMP
      triggers these physiological responses have remained largely unknown. Notably, a
      candidate riboswitch class called ydaO associates with numerous genes involved in
      these same processes. Although a representative ydaO motif RNA recently was
      reported to weakly bind ATP, we report that numerous members of this noncoding
      RNA class selectively respond to c-di-AMP with subnanomolar affinity. Our
      findings resolve the mystery regarding the primary ligand for this extremely
      common riboswitch class and expose a major portion of the super-regulon of genes
      that are controlled by the widespread bacterial second messenger c-di-AMP. 

PMID- 24141189
TI  - The stromal compartments in pancreatic cancer: are there any therapeutic targets?
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant stromal
      response also known as a desmoplastic reaction. Pancreatic Stellate Cells have
      been identified as playing a key role in pancreatic cancer desmoplasia. There is
      accumulating evidence that the stroma contributes to tumour progression and to
      the low therapeutic response of PDAC patients. In this review we described the
      main actors of the desmoplastic reaction within PDAC and novel therapeutic
      approaches that are being tested to block the detrimental function of the stroma.

PMID- 24141190
TI  - Aiming at the sweet side of cancer: aberrant glycosylation as possible target for
      personalized-medicine.
AB  - One of the frontiers in cancer personalized-medicine aims at glycosylation. Cells
      are covered with a dense sugar coat of glycolipids, glycoproteins and free
      glycans. In cancer, the characteristic cell surface glycosylation is frequently
      transformed due to altered expression of glycan-modifying enzymes. This often
      leads to aberrant expression of sialic acids (Sia) that cap glycan-chains.
      Additionally, dietary intake of the non-human Sia N-glycolylneuraminic acid
      (Neu5Gc) leads to natural metabolic-glycoengineering of human carcinomas that
      accumulate and express Neu5Gc. This Sia provokes a polyclonal anti-Neu5Gc xeno
      autoantibodies response that can exacerbate cancer. This review highlights cancer
      associated changes in Sia expression and their potential for personalized
      theranostics. 

PMID- 24141193
TI  - The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF
      Tu.
AB  - Fic proteins are ubiquitous in all of the domains of life and have critical roles
      in multiple cellular processes through AMPylation of (transfer of AMP to) target
      proteins. Doc from the doc-phd toxin-antitoxin module is a member of the Fic
      family and inhibits bacterial translation by an unknown mechanism. Here we show
      that, in contrast to having AMPylating activity, Doc is a new type of kinase that
      inhibits bacterial translation by phosphorylating the conserved threonine
      (Thr382) of the translation elongation factor EF-Tu, rendering EF-Tu unable to
      bind aminoacylated tRNAs. We provide evidence that EF-Tu phosphorylation diverged
      from AMPylation by antiparallel binding of the NTP relative to the catalytic
      residues of the conserved Fic catalytic core of Doc. The results bring insights
      into the mechanism and role of phosphorylation of EF-Tu in bacterial physiology
      as well as represent an example of the catalytic plasticity of enzymes and a
      mechanism for the evolution of new enzymatic activities. 

PMID- 24141194
TI  - Enzyme mechanisms: What's up 'Doc'?

PMID- 24141195
TI  - Topochemistry of alkaline, alkaline-peroxide and hydrotropic pretreatments of
      common reed to enhance enzymatic hydrolysis efficiency.
AB  - Common reed was studied as raw material for sugar bioconversion. The low
      temperature alkaline, alkaline-peroxide and hydrotropic pretreatments were
      employed to overcome the recalcitrance of reed before enzymatic hydrolysis. After
      pretreatments, lignin was efficiently decreased from the fiber cell wall. Xylan
      was significantly reduced by hydrotropic pretreatment as well. The surface
      chemical compositions of reed before and after pretreatments were investigated by
      X-ray spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF
      SIMS). Reed had a high surface coverage by lignin. Hydrotropic pretreatment was
      outstanding to decrease the surface coverage by lignin and expose the
      polysaccharides to fiber surface. The surface lignin reduction was also supported
      by attenuated total reflectance (ATR)-FTIR results. Furthermore, the topochemical
      modification of the fiber wall by hydrotropic pretreatment could improve the
      fiber digestibility, and thus the maximum glucan and xylan yields with the
      cellulase dosage of 20 FPU/g raised to 93.1% and 25.5%, respectively.

PMID- 24141196
TI  - The origin of diffuse scattering in crystalline carbon tetraiodide.
AB  - Total scattering neutron powder diffraction measurements were performed on the
      tetragonal phase (a=6.4202(5) A, c=9.5762(12) A) of CI4. The experiments were
      followed by reverse Monte Carlo (for powder diffraction) modelling. Detailed
      analyses of the resulting particle configurations revealed that the observed
      diffuse scattering originates from the libration of the molecules. By examining
      the partial radial distribution functions a distinct carbon-iodine peak at 4.5 A
      is found, which appears as a consequence of corner-to-face mutual alignment of
      two molecules. The occurrence of edge-to-edge alignments is also significant
      within the first carbon-carbon coordination shell.

PMID- 24141199
TI  - Definition, incidence and etiology: what's new in the 21st century?
AB  - Actually, achalasia can be defined as a primary esophageal motor disorder
      characterized by esophageal aperistalsis and abnormal post-deglutitive lower
      esophageal sphincter (LES) relaxation. Its incidence varies from 0.03 to 1.63
      cases per 100,000 people per year and increases with age, while the prevalence is
      almost 10/100,000 with no difference between the sexes. Regarding etiology, the
      most frequent histologic alteration is represented by the loss of the myenteric
      nerve fibers regulating inhibitory nitrergic neurotransmission in the LES, with
      the presence of a lymphocytic infiltrate and collagen deposition. The cause of
      this loss remains unclear. Among the theories proposed, the infectious,
      hereditary and autoimmune etiologies have been widely investigated. The only
      infectious agent identified as a cause of achalasia is Trypanosoma Cruzi,
      responsible of Chagas' disease. Regarding hereditary component, in rare cases
      achalasia presents as part of a genetic syndrome such as Down syndrome, Allgrove
      syndrome and familial visceral neuropathy. Although, no disease-specific gene has
      been identified. The autoimmune hypothesis has focused on the association of
      specific HLA classes with achalasia. However, no consistent association has been
      observed across studies. Despite increasing understanding of the physiopathology
      of achalasia, its etiology remains largely unknown. The onset of the disease is
      characterized by chronic inflammation of the myenteric plexus of the esophagus
      secondary to an environmental insult. Probably, genetic factors are involved in
      the development of achalasia, although the precise molecular basis of the disease
      has not been identified.

PMID- 24141198
TI  - Inhibition of p38 MAPK Phosphorylation Is Critical for Bestatin to Enhance ATRA
      Induced Cell Differentiation in Acute Promyelocytic Leukemia NB4 Cells.
AB  - Bestatin has been known as an immunomodulating agent in anti-leukemia treatment.
      The mechanism by which Bestatin enhances all-trans retinoic acid (ATRA)-induced
      cell differentiation of acute promyelocytic leukemia (APL) cells is generally
      attributed to inhibition of cell surface CD13/aminopeptidase N activity. Bestatin
      also exerts its biological activities besides its ability to inhibit
      aminopeptidase N enzymatic activity. This article provides data to support an
      alternative mechanism regarding an important role of inhibition of p38 mitogen
      activated protein kinase (MAPK) signal pathway in Bestatin's anti-leukemia
      effect. Bestatin enhanced ATRA-induced differentiation and inhibited ATRA-driven
      phosphorylation of p38 MAPK in ATRA-sensitive APL NB4 cells. In contrast,
      Bestatin could not reverse the differentiation block in ATRA-resistant APL MR2
      cells, in which ATRA was unable to induce phosphorylation of p38 MAPK. Moreover,
      CD13 ligation with anti-CD13 antibody WM-15 resulted in phosphorylation of p38
      MAPK, reduced the inhibition of Bestatin on the phosphorylation of p38 MAPK, and
      completely abolished the enhancement of Bestatin on ATRA-inducing differentiation
      in NB4 cells. This study shows that inhibition of p38 MAPK phosphorylation is
      critical for Bestatin to enhance ATRA-induced cell differentiation in ATRA
      sensitive APL NB4 cells. Results suggested that pharmacological inhibition of the
      p38 MAPK pathway might enhance ATRA-dependent differentiation. 

PMID- 24141200
TI  - Health protective effects of carotenoids and their interactions with other
      biological antioxidants.
AB  - Carotenoids are natural pigments attracting attention of physicists, chemists and
      biologists due to their multiple functions in the nature. While carotenoids have
      unusually high extinction coefficients, they do not exhibit adequate emission.
      This fact has resulted in detailed studies of photophysical and photochemical
      properties of carotenoids and their role as light-harvesting pigments in
      photosynthesis. Carotenoids are abundantly present in fruits and vegetables and
      are considered as important species with beneficial effect on human health by
      decreasing the risk of various diseases, particularly decreasing the incidence of
      cancers and eye disease. More trials are needed to ascertain the role of
      carotenoids in prevention of cardiovascular disease and metabolic disease.
      Carotenoids effectively scavenge peroxyl radicals and act predominantly as
      antioxidants. However, under conditions of increased concentration of oxygen and
      carotenoid concentration, beta-carotene was found to exhibit prooxidant
      behaviour. Photophysical properties of carotenoids and conditions affecting a
      switch between antioxidant and prooxidant behaviour of carotenoids are the main
      aims of this review. In addition, the localization of carotenoids in biological
      membranes, their interactions and reactions with ascorbic acid (vitamin C) and
      alpha-tocopherol (vitamin E) as well as their redox potentials are discussed in
      view of their antioxidant properties as beneficial species in preventing various
      diseases. 

PMID- 24141201
TI  - Synthetic cannabinoid quinones: preparation, in vitro antiproliferative effects
      and in vivo prostate antitumor activity.
AB  - Chromenopyrazolediones have been designed and synthesized as anticancer agents
      using the multi-biological target concept that involves quinone cytotoxicity and
      cannabinoid antitumor properties. In cell cytotoxicity assays, these
      chromenopyrazolediones have antiproliferative activity against human prostate
      cancer and hepatocellular carcinoma. It has been shown that the most potent,
      derivative 4 (PM49), inhibits prostate LNCaP cell viability (IC50 = 15 MUM)
      through a mechanism involving oxidative stress, PPARgamma receptor and partially
      CB1 receptor. It acts on prostate cell growth by causing G0/G1 phase arrest and
      triggering apoptosis as assessed by flow cytometry measurements. In the in vivo
      treatment, compound 4 at 2 mg/kg, blocks the growth of LNCaP tumors and reduces
      the growth of PC-3 tumors generated in mice. These studies suggest that 4 is a
      good potential anticancer agent against hormone-sensitive prostate cancer.

PMID- 24141197
TI  - Mammalian Prion protein expression in yeast; a model for transmembrane insertion.
AB  - The prion protein (PrP), a GPI-anchored glycoprotein, is inefficiently secreted
      by mammalian microsomes, 50% being found as transmembrane (TM) proteins with the
      central TM1 segment spanning the membrane. TM1 hydrophobicity is marginal for
      lateral membrane insertion, which is primarily driven by hydrophobic interaction
      between the ER translocon and substrates in transit. Most inserted TM1 has its N
      terminus in the ER lumen (Ntm orientation), as expected for arrest of normal
      secretion. However, 20% is found in inverted Ctm orientation. These are minor
      species in vivo, presumably a consequence of efficient quality control. PrP
      mutations that increase TM1 hydrophobicity result in increased Ctm insertion,
      both in vitro and in mouse brain, and a strong correlation is found between
      CtmPrP insertion and neuropathology in transgenic mice; a copper-dependent
      pathogenicity mechanism is suggested. PrP fusions with a C-terminal epitope tag,
      when expressed in yeast cells at moderate levels, appear to interact efficiently
      with the translocon, providing a useful model for testing the effects of PrP
      mutations on TM insertion and orientation. However, secretion of PrP by the
      mammalian translocon requires the TRAP complex, absent in yeast, where
      essentially all PrP ends up as TM species, 85-90% Ntm and 10-15% Ctm. Although
      yeast is, therefore, an incomplete mimic of mammalian PrP trafficking, effects on
      Ctm insertion of mutations increasing TM1 hydrophobicity closely reflect those
      seen in vitro. Electrostatic substrate-translocon interactions are a major
      determinant of TM protein insertion orientation and the yeast model was used to
      investigate the role of the large negative charge difference across TM1, a likely
      cause of translocation delay that would favor TM insertion and Ctm orientation.
      An increase in DeltaCh from -5 to -7 caused a marked increase in Ctm insertion,
      while a decrease to -3 or -1 allowed 35 and about 65% secretion, respectively.
      Utility of the yeast model and the role of this charge difference in driving PrP
      membrane insertion are confirmed. 

PMID- 24141202
TI  - Synthesis, characterization, and anticancer activity of ruthenium(II)-beta
      carboline complex.
AB  - Four [Ru(tpy)(N-N)(L)] type complexes: [Ru(tpy)(bpy)(Nh)](2+) (Ru1, tpy =
      2,2';6',2"-terpyridine, bpy = 2'2-bipyridine, Nh = Norharman),
      [Ru(tpy)(phen)(Nh)](2+) (Ru2, phen = 1,10-phenanthroline), [Ru(tpy)(dpa)(Nh)](2+)
      (Ru3, dpa = 2,2'-dipyridylamine) and [Ru(tpy)(dip)(Nh)](2+) (Ru4, dip = 4,7
      diphenyl-1,10-phenanthroline) were presented as anticancer drugs. In vitro
      cytotoxicity assays indicated that these complexes showed anticancer activity
      against various cancer cells. Flow cytometry and signaling pathways analysis
      demonstrated that these complexes induced apoptosis via the mitochondrial
      pathway, as evidenced by the loss of mitochondrial membrane potential and the
      release of cytochrome c. The resulting accumulation of p53 proteins from
      phosphorylation at serine-15 and serine-392 was correlated with an increase in
      p21 and caspase activation. Taken together, these findings suggested that Ru1-Ru4
      may contribute to the future development of improved chemotherapeutics against
      human cancers.

PMID- 24141205
TI  - Cognitive consistency and math-gender stereotypes in Singaporean children.
AB  - In social psychology, cognitive consistency is a powerful principle for
      organizing psychological concepts. There have been few tests of cognitive
      consistency in children and no research about cognitive consistency in children
      from Asian cultures, who pose an interesting developmental case. A sample of 172
      Singaporean elementary school children completed implicit and explicit measures
      of math-gender stereotype (male=math), gender identity (me=male), and math self
      concept (me=math). Results showed strong evidence for cognitive consistency; the
      strength of children's math-gender stereotypes, together with their gender
      identity, significantly predicted their math self-concepts. Cognitive consistency
      may be culturally universal and a key mechanism for developmental change in
      social cognition. We also discovered that Singaporean children's math-gender
      stereotypes increased as a function of age and that boys identified with math
      more strongly than did girls despite Singaporean girls' excelling in math. The
      results reveal both cultural universals and cultural variation in developing
      social cognition. 

PMID- 24141207
TI  - Silver environment and covalent network rearrangement in GeS3-Ag glasses.
AB  - The structure of Ag-doped GeS3 glasses (0, 15, 20, 25 at.% Ag) was investigated
      by diffraction techniques and extended x-ray absorption fine structure
      measurements. Structural models were obtained by fitting the experimental
      datasets simultaneously by the reverse Monte Carlo simulation technique. It is
      observed that Ge has mostly S neighbours in GeS3, but Ge-Ge bonds appear already
      at 15% Ag content. Sulfur has ~2 S/Ge neighbours over the whole concentration
      range, while the S-Ag coordination number increases with increasing Ag content.
      Ag-Ag pairs can already be found at 15% Ag. The Ag-S mean coordination number
      changes from 2.17 +/- 0.2 to 2.86 +/- 0.2 between 15% and 25% Ag content. Unlike
      the As-S network in AsS2-25Ag glass, the Ge-S network is not fragmented upon Ag
      doping of GeS3 glass.

PMID- 24141206
TI  - Reference values of elements in human hair: a systematic review.
AB  - BACKGROUND: The lack of systematic review on reference values of elements in
      human hair with the consideration of methodological approach. The absence of
      worldwide accepted and implemented universal reference ranges causes that hair
      mineral analysis has not become yet a reliable and useful method of assessment of
      nutritional status and exposure of individuals. OBJECTIVES: Systematic review of
      reference values of elements in human hair. DATA SOURCES: PubMed, ISI Web of
      Knowledge, Scopus. STUDY ELIGIBILITY CRITERIA: Humans, hair mineral analysis,
      elements or minerals, reference values, original studies. RESULTS: The number of
      studies screened and assessed for eligibility was 52. Eventually, included in the
      review were 5 papers. The studies report reference ranges for the content of
      elements in hair: macroelements, microelements, toxic elements and other
      elements. Reference ranges were elaborated for different populations in the years
      2000-2012. The analytical methodology differed, in particular sample preparation,
      digestion and analysis (ICP-AES, ICP-MS). Consequently, the levels of hair
      minerals reported as reference values varied. CONCLUSIONS: It is necessary to
      elaborate the standard procedures and furtherly validate hair mineral analysis
      and deliver detailed methodology. Only then it would be possible to provide
      meaningful reference ranges and take advantage of the potential that lies in Hair
      Mineral Analysis as a medical diagnostic technique.

PMID- 24141204
TI  - Bioinspired greigite magnetic nanocrystals: chemical synthesis and biomedicine
      applications.
AB  - Large scale greigite with uniform dimensions has stimulated significant demands
      for applications such as hyperthermia, photovoltaics, medicine and cell
      separation, etc. However, the inhomogeneity and hydrophobicity for most of the as
      prepared greigite crystals has limited their applications in biomedicine. Herein,
      we report a green chemical method utilizing beta-cyclodextrin (beta-CD) and
      polyethylene glycol (PEG) to synthesize bioinspired greigite (Fe3S4) magnetic
      nanocrystals (GMNCs) with similar structure and magnetic property of magnetosome
      in a large scale. beta-CD and PEG is responsible to control the crystal phase and
      morphology, as well as to bound onto the surface of nanocrystals and form polymer
      layers. The GMNCs exhibit a transverse relaxivity of 94.8 mM-1 s-1 which is as
      high as iron oxide nanocrystals, and an entrapment efficiency of 58.7% for
      magnetic guided delivery of chemotherapeutic drug doxorubicin. Moreover, enhanced
      chemotherapeutic treatment of mice tumor was obtained via intravenous injection
      of doxorubicin loaded GMNCs.

PMID- 24141203
TI  - Structure-activity relationship (SAR) and preliminary mode of action studies of 3
      substituted benzylthioquinolinium iodide as anti-opportunistic infection agents.
AB  - Opportunistic infections are devastating to immunocompromised patients. And in
      especially sub-Saharan Africa where the AIDS epidemic is still raging, the
      mortality rate was recently as high as 70%. The paucity of anti-opportunistic
      drugs, the decreasing efficacy and the development of resistance against the
      azoles and even amphotericin B have stimulated the search for new drugs with new
      mechanisms of action. In a previous work, we showed that a new chemotype derived
      from the natural product cryptolepine displayed selective toxicity against
      opportunistic pathogens with minimal cytotoxicity to normal cells. In this
      manuscript, we report the design and synthesis of substituted
      benzylthioquinolinium iodides, evaluated their anti-infective properties and
      formulated some initial structure-activity relationships around phenyl ring A
      from the original natural product. The sensitivity of the most potent analog 10l,
      to selected strains of C. cerevisiae was also evaluated leading to the
      observation that this scaffold may have a different mode of action from its
      predecessor, cryptolepine. 

PMID- 24141208
TI  - Occurrence of Giardia duodenalis assemblages in alpacas in the Andean region.
AB  - In this study, 352 fecal samples were analyzed for G. duodenalis from alpaca
      mothers and crias from three different areas of highland in Peru. The
      triosephosphate isomerase (TPI) gene of Giardia was amplified using a nested PCR
      protocol. Forty-six G. duodenalis-PCR positive samples were sequenced. G.
      duodenalis assemblage A was the most frequent followed by assemblage E. The
      former was seen in 37 animals whereas the latter was seen in nine. Most of the
      assemblage A infections were caused by the A1 subtype of sub-assemblage AI,
      except for three, which were caused by the A2 subtype of sub-assemblage AI.
      Assemblage A was found in all three geographic regions, while assemblage E was
      detected in crias from two regions. Among the four alpaca mothers positive for
      Giardia, three had assemblage AI and one had assemblage AII. Results of this
      study indicate that possible zoonotic transmission human to alpacas. 

PMID- 24141220
TI  - Drug discovery: Rethinking cellular drug response.

PMID- 24141224
TI  - 'Examining the evidence about psychological treatments for chronic pain: time for
      a paradigm shift?' by Morley et al.

PMID- 24141218
TI  - Sirtuins: Longevity focuses on NAD+.

PMID- 24141226
TI  - Length-dependent thermoelectric characteristics of silicon nanowires on plastics
      in a relatively low temperature regime in ambient air.
AB  - We report on the thermoelectric characteristics of p-type silicon nanowires (NWs)
      on plastics in the relatively low temperature regime below 47  degrees C, and for
      temperature differences of less than 10 K in ambient air. Thermal profile images
      are utilized to directly determine the temperature difference in the NWs
      generated by Joule heating in air. The Seebeck coefficient of the NWs increases
      from 294 to 414 MUV K(-1) as the NW length varies from 40 to 280 MUm. For a
      temperature difference of 7 K, the maximal Seebeck voltage can be estimated to be
      2.7 mV for NWs with a length of 280 MUm. In contrast, the output power is
      maximized for NWs length of 240 MUm. The maximized output power obtained
      experimentally in this study is 2.1 pW at a temperature difference of 6 K. The
      thermoelectric characteristics are analyzed and discussed.

PMID- 24141225
TI  - Is second pain worse than the first?

PMID- 24141209
TI  - Routine vaccination against MenB: considerations for implementation.
AB  - Effective polysaccharide(conjugate) vaccines against Neisseria meningitidis
      serogroups A, C, W, and Y have been widely used, but serogroup B meningococci
      remain a major cause of severe invasive meningococcal disease (IMD) worldwide,
      especially in infants. Recently, a vaccine, 4CMenB (Bexsero((r))), containing
      three recombinant proteins, and outer membrane vesicles (OMV) derived from a
      serogroup B meningococcal strain (MenB) has been licensed in Europe and Australia
      and is indicated for persons aged 2 mo or older. This article discusses what
      should be considered to enable a successful implementation of a broad coverage
      MenB vaccine in national immunization programs. Epidemiology data, vaccine
      characteristics including vaccine coverage, immunogenicity, post-implementation
      surveillance and costs are relevant aspects that should be taken into account
      when selecting an appropriate immunization strategy. The potential impact on
      strain variation and carriage, as well as monitoring vaccine effectiveness, and
      rare but potentially serious adverse events are points that need to be included
      in a post-implementation surveillance plan. 

PMID- 24141219
TI  - Membrane proteins: Through thick and thin.

PMID- 24141228
TI  - Preoperative work-up.
AB  - Despite several advances in the understanding of the pathophysiology of
      achalasia, treatment remains palliative as the neuronal defect of the disease
      seems to be irreversible. Currently, the most effective treatment options are
      graded endoscopic pneumatic dilation and laparoscopic Heller myotomy with partial
      fundoplication. Although both treatments seem to have similar efficacy in the
      short-term, the durability of surgical myotomy makes it the favored approach in
      young patients and in those who want to avoid frequent repeated interventions.
      Predictors of treatment response have been well defined and should be considered
      when one therapeutic option is chosen over another. In addition, patient
      preferences and local are the major are major factors that determine treatment
      choice. A complete preoperative work up, evaluating patient and disease
      characteristics, is a key element of a successful treatment.

PMID- 24141227
TI  - Dithiolopyrrolone natural products: isolation, synthesis and biosynthesis.
AB  - Dithiolopyrrolones are a class of antibiotics that possess the unique
      pyrrolinonodithiole (4H-[1,2] dithiolo [4,3-b] pyrrol-5-one) skeleton linked to
      two variable acyl groups. To date, there are approximately 30 naturally occurring
      dithiolopyrrolone compounds, including holomycin, thiolutin, and aureothricin,
      and more recently thiomarinols, a unique class of hybrid marine bacterial natural
      products containing a dithiolopyrrolone framework linked by an amide bridge with
      an 8-hydroxyoctanoyl chain linked to a monic acid. Generally, dithiolopyrrolone
      antibiotics have broad-spectrum antibacterial activity against various
      microorganisms, including Gram-positive and Gram-negative bacteria, and even
      parasites. Holomycin appeared to be active against rifamycin-resistant bacteria
      and also inhibit the growth of the clinical pathogen methicillin-resistant
      Staphylococcus aureus N315. Its mode of action is believed to inhibit RNA
      synthesis although the exact mechanism has yet to be established in vitro. A
      recent work demonstrated that the fish pathogen Yersinia ruckeri employs an RNA
      methyltransferase for self-resistance during the holomycin production. Moreover,
      some dithiolopyrrolone derivatives have demonstrated promising antitumor
      activities. The biosynthetic gene clusters of holomycin have recently been
      identified in S. clavuligerus and characterized biochemically and genetically.
      The biosynthetic gene cluster of thiomarinol was also identified from the marine
      bacterium Pseudoalteromonas sp. SANK 73390, which was uniquely encoded by two
      independent pathways for pseudomonic acid and pyrrothine in a novel plasmid. The
      aim of this review is to give an overview about the isolations,
      characterizations, synthesis, biosynthesis, bioactivities and mode of action of
      this unique family of dithiolopyrrolone natural products, focusing on the period
      from 1940s until now. 

PMID- 24141229
TI  - Ultrasonography of the cervical spine: an in vitro anatomical validation model.
AB  - BACKGROUND: Anatomical validation studies of cervical ultrasound images are
      sparse. Validation is crucial to ensure accurate interpretation of cervical
      ultrasound images and to develop standardized reliable ultrasound procedures to
      identify cervical anatomical structures. The aim of this study was to acquire
      validated ultrasound images of cervical bony structures and to develop a reliable
      method to detect and count the cervical segmental levels. METHODS: An anatomical
      model of a cervical spine, embedded in gelatin, was inserted in a specially
      developed measurement device. This provided ultrasound images of cervical bony
      structures. Anatomical validation was achieved by laser light beams projecting
      the center of the ultrasound image on the cervical bony structures through a
      transparent gelatin. RESULTS: Anatomically validated ultrasound images of
      different cervical bony structures were taken from dorsal, ventral, and lateral
      perspectives. Potentially relevant anatomical landmarks were defined and
      validated. Test/retest analysis for positioning showed a reproducibility with an
      intraclass correlation coefficient for single measures of 0.99. Besides providing
      validated ultrasound images of bony structures, this model helped to develop a
      method to detect and count the cervical segmental levels in vivo at long-axis
      position, in a dorsolateral (paramedian) view at the level of the laminae,
      starting from the base of the skull and sliding the ultrasound probe caudally.
      CONCLUSIONS: Ultrasound bony images of the cervical vertebrae were validated with
      an in vitro model. Anatomical bony landmarks are the mastoid process, the
      transverse process of C1, the tubercles of C6 and C7, and the cervical laminae.
      Especially, the cervical dorsal laminae serve best as anatomical bony landmarks
      to reliably detect the cervical segmental levels in vivo.

PMID- 24141231
TI  - A place to stand.

PMID- 24141233
TI  - NiS--an unusual self-doped, nearly compensated antiferromagnetic metal.
AB  - NiS, exhibiting a text-book example of a first-order transition with many unusual
      properties at low temperatures, has been variously described in terms of
      conflicting descriptions of its ground state during the past several decades. We
      calculate these physical properties within first-principle approaches based on
      the density functional theory and conclusively establish that all experimental
      data can be understood in terms of a rather unusual ground state of NiS that is
      best described as a self-doped, nearly compensated, antiferromagnetic metal,
      resolving the age-old controversy. We trace the origin of this novel ground state
      to the specific details of the crystal structure, band dispersions and a sizable
      Coulomb interaction strength that is still sub-critical to drive the system in to
      an insulating state. We also show how the specific antiferromagnetic structure is
      a consequence of the less-discussed 90 degrees  and less than 90 degrees 
      superexchange interactions built in to such crystal structures. 

PMID- 24141235
TI  - Reverse Monte Carlo study of spherical sample under non-periodic boundary
      conditions: the structure of Ru nanoparticles based on x-ray diffraction data.
AB  - A new method to fit experimental diffraction data with non-periodic structure
      models for spherical particles was implemented in the reverse Monte Carlo
      simulation code. The method was tested on x-ray diffraction data for ruthenium
      (Ru) nanoparticles approximately 5.6 nm in diameter. It was found that the atomic
      ordering in the ruthenium nanoparticles is quite distorted, barely resembling the
      hexagonal structure of bulk Ru. The average coordination number for the bulk
      decreased from 12 to 11.25. A similar lack of structural order has been observed
      with other nanoparticles (e.g. Petkov et al 2008 J. Phys. Chem. C 112 8907-11)
      indicating that atomic disorder is a widespread feature of nanoparticles less
      than 10 nm in diameter.

PMID- 24141234
TI  - Tracking the stilbene photoisomerization in the S(1) state using RASSCF.
AB  - In this work we compute the S1 potential energy curve responsible for stilbene
      cis-trans photoisomerisation employing the RASSCF approach, since the standard
      CASPT2//CASSCF protocol appears to be unsatisfactory in describing the stilbene
      S1 state. We find that RASSCF calculations, which are based on relatively few
      (but well chosen) configurations, produce qualitatively correct results and
      accurate relative excited state energies, both in the twisted and in the cis and
      trans regions of stilbene. 

PMID- 24141236
TI  - Second harmonic generation reveals collagen fibril remodeling in fibroblast
      populated collagen gels.
AB  - Remodeling of collagen fibrils is involved in a variety of physiological and
      pathological processes including development, tissue repair, and metastasis.
      Fibroblast-populated collagen gel contraction has been employed as a model system
      to investigate the collagen fibril remodeling within three-dimensional collagen
      matrices. Research on collagen gel contraction is also important for
      understanding the mechanism underlying connective tissue repair, and for design
      considerations for engineered tissues in regenerative medicine. Second harmonic
      generation (SHG) is a non-linier optical effect by which well-ordered protein
      assemblies, including collagen fibrils, can be visualized without any labeling,
      and used for a noninvasive imaging of collagen fibrils in the skin. Here we
      demonstrate that the remodeling of collagen fibrils in the fibroblast-populated
      collagen gel can be analyzed by SHG imaging with a multiphoton microscope. Two
      models of collagen gel contraction (freely versus restrained contraction) were
      prepared, and orientation of fibroblasts, density, diameter, and distribution of
      collagen fibrils were examined by multiphoton fluorescent and SHG microscopy.
      Three-dimensional construction images revealed vertical and horizontal
      orientation of fibroblasts in freely and restrained gel contraction,
      respectively. Quantitative analysis indicated that collagen fibrils were
      accumulated within the gel and assembled into the thicker bundles in freely but
      not restrained collagen gel contraction. We also found that actomyosin
      contractility was involved in collagen fibril remodeling. This study elucidates
      how collagen fibrils are remodeled by fibroblasts in collagen gel contraction,
      and also proves that SHG microscopy can be used for the investigation of the
      fibroblast-populated collagen gel. 

PMID- 24141237
TI  - Priority organic compounds in wastewater effluents from the Mediterranean and
      Atlantic basins of Andalusia (Spain).
AB  - A comprehensive survey of the occurrence of organic compounds in 30 wastewater
      (WW) effluent samples from 21 urban wastewater treatment plants (WWTPs) from both
      secondary and tertiary treatments was carried out in the Mediterranean and
      Atlantic basins of the Andalusia region (south of Spain). For each sample, a
      total of 226 compounds including pesticides and some transformation products,
      polycyclic aromatic hydrocarbons (PAHs), phenolic compounds and volatile organic
      compounds (VOCs) were monitored with the aim of evaluating their occurrence in
      urban WW effluents. Compounds belonging to each class were detected. Among
      pesticides, insecticides such as clorfenvinphos and diazinon as well as
      herbicides such as diuron, sebuthylazine, terbuthylazine and terbuthylazine
      desethyl were the most frequently detected. The ubiquity of some compounds such
      as fluorene, phenanthrene and pyrene was also demonstrated. The compounds
      evaluated were detected at low concentrations (in general below 1 MUg L(-1)),
      except 4-tert-octylphenol, which was detected at extremely high concentrations
      (up to 443 MUg L(-1)). PAHs and VOCs were the compounds most frequently detected
      in the assayed samples, and they are the main sources of contamination in WWTPs,
      as well as some herbicides and transformation products. 

PMID- 24141238
TI  - Bone loss in surgically ovariectomized premenopausal women is associated with T
      lymphocyte activation and thymic hypertrophy.
AB  - Postmenopausal osteoporosis is associated with estrogen deficiency and rapid bone
      loss. The mechanism by which estrogen deficiency results in bone loss has not
      been fully explained. Studies in mice rendered acutely estrogen deficient by
      ovariectomy have suggested that estrogen deficiency results in an activated T
      lymphocyte phenotype and increased production of pro-osteoclastic cytokines. The
      aim of this study was to translate these findings from mouse models that suggest
      that the T lymphocyte plays an important role in the etiology of postmenopausal
      osteoporosis. We recruited premenopausal women who underwent ovariectomy for
      benign gynecologic conditions or for prophylaxis against ovarian cancer and a
      group of matched control women without ovariectomy (OVX). Subjects provided blood
      samples to characterize T-lymphocyte phenotype by flow cytometry and for T
      lymphocyte culture and collection of conditioned media. Bone mineral density at
      the lumbar spine and left femoral neck was performed annually for 2 years, and
      volumetric measurements by computed tomography (CT) of the thymus were obtained
      during the first 6 months. We enrolled 6 patients who underwent OVX and 13
      control women. The OVX subjects had a significant loss of bone mineral density at
      the lumbar spine and left femoral neck. The volumetric thymus measurements
      suggested an increase in thymus size in the OVX subjects but did not reach
      statistical significance owing to the small sample size. The T-lymphocyte
      phenotype in the OVX subjects demonstrated increased T-lymphocyte activation by
      flow cytometry compared to the control subjects. Our findings support the
      hypothesis that estrogen deficiency leads to an activated T-lymphocyte phenotype,
      which may contribute to the bone loss seen in estrogen deficiency. Larger
      clinical studies are necessary to confirm these findings. 

PMID- 24141240
TI  - Neurophysiological marker of inhibition distinguishes language groups on a non
      linguistic executive function test.
AB  - Successful interaction with the environment depends on flexible behaviors which
      require shifting attention, inhibiting primed responses, ignoring distracting
      information, and withholding motor responses. These abilities, termed executive
      function (EF), are believed to be mediated by inhibitory processes in the frontal
      lobes. Superior performance on EF tests (i.e., faster reaction times (RT), and
      fewer errors) has been shown in bilinguals compared to monolingual speakers.
      However, findings are inconsistent, and no study has directly linked this
      bilingual advantage to frontal lobe inhibitory processes. To clarify this
      uncertainty, we concomitantly tested neural inhibitory processes and behavioral
      responses on an EF test in bilinguals and monolinguals. Specifically, we compared
      English monolinguals (N=15) to Spanish/English bilinguals (N=13) on event-related
      brain potentials (ERP) during a non-linguistic, auditory Go/NoGo task, a task
      linked to non-motor, cognitive inhibition in monolinguals. Participants responded
      with a button press on trials in which target tone-pairs (Go trials) were
      presented and withheld their responses on non-target trials (NoGo trials).
      Results revealed significantly greater inhibition (i.e., greater mean N2
      amplitude) in bilinguals compared to monolinguals during NoGo trials even though
      both groups performed the task equally well (i.e., withheld a motor response). On
      Go trials where participants pressed a response button, neither ERPs nor RT
      distinguished the groups. Additionally, scores on a second language proficiency
      test (i.e., English in our bilingual group) were positively correlated with N2
      amplitude. These findings are the first to directly link this bilingual advantage
      to a neural correlate of inhibition and to reveal that inhibition in bilinguals
      is moderated by second language proficiency. Results are discussed in the context
      of plasticity, and we propose that evaluating bilinguals at varying levels of
      second-language proficiency may serve as a model of human neuroplasticity. 

PMID- 24141241
TI  - Fast determination of 90Sr/90Y activity in milk by Cherenkov counting.
AB  - Cherenkov counting of the 90Sr/90Y pure beta emitters is an attractive method for
      90Sr activity determination, but the color quenching effect may be significant,
      especially for strongly colored or semi-opaque media. A quench correction method
      based on the external source of some liquid scintillation systems (named ESAR -
      external source area ratio) was proposed and checked for aqueous solutions and
      was proved to be effective also for urine samples. In the present work, the
      application of the ESAR method for fast determination of 90Sr/90Y activity in
      milk samples is described.

PMID- 24141242
TI  - Direct light-up of cAMP derivatives in living cells by click reactions.
AB  - 8-Azidoadenosine 3',5'-cyclic monophosphate (8-azido cAMP) was directly detected
      in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP
      derivatives by fluorescence light-up. Fluorescence emission was generated by two
      non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated
      cyclooctyne (DIFO) reagent as a probe. The azide-alkyne cycloaddition reaction
      between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The
      fluorescence emission serves as a way to probe 8-azido cAMP in cells. 

PMID- 24141239
TI  - Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are
      heightened in obese patients.
AB  - OBJECTIVE: The American Diabetes Association has called for further research on
      how patients' demographics should determine drug choices for individuals with
      type 2 diabetes mellitus (T2DM). Here, using in-depth physiology studies, we
      investigate whether obese patients with T2DM are likely to benefit from
      thiazolidinediones, medications with a known adverse effect of weight gain.
      MATERIALS AND METHODS: Eleven obese and 7 nonobese individuals with T2DM
      participated in this randomized, placebo-controlled, double-blind, crossover
      study. Each subject underwent a pair of "stepped" pancreatic clamp studies with
      subcutaneous adipose tissue biopsies after 21 days of pioglitazone (45 mg) or
      placebo. RESULTS: Obese subjects demonstrated significant decreases in insulin
      resistance and many adipose inflammatory parameters with pioglitazone relative to
      placebo. Specifically, significant improvements in glucose infusion rates,
      suppression of hepatic glucose production, and whole fat expression of certain
      inflammatory markers (IL-6, IL-1B, and inducible nitric oxide synthase) were
      observed in the obese subjects but not in the nonobese subjects. Additionally,
      adipose tissue from the obese subjects demonstrated reduced infiltration of
      macrophages, dendritic cells, and neutrophils as well as increased expression of
      factors associated with fat "browning" (peroxisome proliferator-activated
      receptor gamma coactivator-1alpha and uncoupling protein-1). CONCLUSIONS: These
      findings support the efficacy of pioglitazone to improve insulin resistance and
      reduce adipose tissue inflammation in obese patients with T2DM.

PMID- 24141243
TI  - The anti-lung cancer activities of steroidal saponins of P. polyphylla Smith var.
      chinensis (Franch.) Hara through enhanced immunostimulation in experimental Lewis
      tumor-bearing C57BL/6 mice and induction of apoptosis in the A549 cell line.
AB  - P. polyphylla Smith var. chinensis (Franch.) Hara (PPSCFH) has been used as
      medicinal Paris for the prevention and treatment of cancers in China for
      thousands of years. Its main components, steroidal saponins (PRS), have been
      confirmed to inhibit tumor growth. In the present study, the immunostimulation of
      PRS was investigated in Lewis bearing-C57BL/6 mice while the induction of
      apoptosis in A549 cells was also studied. The treatment with PRS (2.5, 5.0 and
      7.5 mg/kg) significantly inhibited tumor, volume, and weight in the C57BL/6 mice.
      The rates of inhibition of PRS (at 2.5, 5.0 and 7.5 mg/kg) were 26.49 +/- 17.30%,
      40.32 +/- 18.91% and 54.94 +/- 16.48%, respectively. The spleen and thymus
      indexes were increased remarkably, while the levels of inflammatory cytokines
      including TNF-alpha, IL-8 and IL-10 in serum were decreased according to ELISA
      assays. For A549 cells, Hoechst 33342 staining and annexin V/PI by flow cytometry
      showed that PRS (0.25, 0.50 and 0.75 mg/mL) induced nuclear changes of A549 cells
      with DNA condensation and fragmentations of chromatin, as well as inducing
      apoptosis. Furthermore, PRS could also attenuate the over-generation of
      intracellular ROS. Western blotting analysis showed a significant decrease on the
      expressions of proinflammatory cytokines MCP-1, IL-6 and TGF-beta1, as well as
      cell adhesion molecule ICAM-1, by treatment with PRS. Our results demonstrated
      that the inhibition of PRS on tumor growth might be associated with the
      amelioration of inflammation responses, induction of apoptosis, as well as the
      decrease of ROS. These results suggested that PRS implied a potential therapeutic
      effect in the lung cancer treatment. 

PMID- 24141245
TI  - Synthesis of bistetrahydroquinolines as potential anticholinesterasic agents by
      double Diels-Alder reactions.
AB  - The tetrahydroquinoline ring system is a unit found in many biologically active
      natural products and pharmacologically relevant therapeutic agents. A new series
      of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder
      reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The
      notable features of this procedure are mild reaction conditions, greater
      selectivity and good yields of products. In addition, the inhibitory activity
      against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of some
      selected derivatives is reported. The feasible binding modes of these active
      compounds, within AChE and BuChE binding sites, were predicted by molecular
      docking experiments and their binding affinity was estimated by means of free
      energy calculations through the MM-GBSA approximation. 

PMID- 24141244
TI  - Antioxidant activity and anti-adipogenic effects of wild herbs mainly cultivated
      in Korea.
AB  - Wild herbs, which are edible plants that grow in mountainous areas, have diverse
      biological effects such as anti-obesity and anti-cancer activities. The aim of
      this study was to evaluate the total phenolic and flavonoid contents as well as
      the antioxidant activity of methanol extracts of Aster scaber, Ligularia
      fischeri, Kalopanax pictus, Codonopsis lanceolata, and Cirsium setidens and to
      assess their effects on lipid accumulation and reactive oxygen species (ROS)
      production during adipogenesis of 3T3-L1 cells. The results revealed that among
      the five studied wild herb extracts, Ligularia fischeri showed the highest total
      phenolic contents (215.8 +/- 14.2 mg GAE/g) and Aster scaber showed the highest
      total flavonoid content (103.9 +/- 3.4 mg RE/g). Furthermore, Aster scaber and
      Ligularia fischeri extracts showed higher antioxidant activity than the other
      wild herbs. Regarding anti-adipogenic activity, the Cirsium setidens extract
      significantly inhibited lipid accumulation (~80%) and ROS production (~50%)
      during adipogenesis of 3T3-L1 cells compared with control cells. These results
      suggest that wild herbs could be used for the development of functional foods as
      well as health promoting and pharmaceutical agents. 

PMID- 24141246
TI  - Oligonucleotide labelling using a fluorogenic "click" reaction with a
      hemicarboxonium salt.
AB  - Two fluorescent streptocyanine labelled oligonucleotides have been synthesized by
      a simple "click" reaction between a non-fluorescent hemicarboxonium salt and
      aminoalkyl functionalized thymidines within the oligonucleotide and their
      spectrophotometric properties have been studied. 

PMID- 24141247
TI  - Endogenous protection derived from activin A/Smads transduction loop stimulated
      via ischemic injury in PC12 cells.
AB  - Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super-
      family, affects many cellular processes, including ischemic stroke. Though the
      neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD)
      injury have already been reported by us, the endogenous role of ActA remains
      poorly understood. To further define the role and mechanism of endogenous ActA
      and its signaling in response to acute ischemic damage, we used an OGD model in
      PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre
      treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We
      found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the
      extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells
      was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our
      results show that ActRII-Ab may augment ischemic injury via blocking of
      transmembrane signal transduction of ActA, which confirmed the existence of
      endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA
      plays an important role in transferring neuronal protective signals inside. It is
      highly possible that ActA transmembrance signaling is a part of the positive feed
      back loop for extracellular ActA secretion. 

PMID- 24141248
TI  - SOCS3-mediated blockade reveals major contribution of JAK2/STAT5 signaling
      pathway to lactation and proliferation of dairy cow mammary epithelial cells in
      vitro.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is a cytokine-induced negative
      feedback-loop regulator of cytokine signaling. More and more evidence has proved
      it to be an inhibitor of signal transducers and activators of transcription 5
      (STAT5). Here, we used dairy cow mammary epithelial cells (DCMECs) to analyze the
      function of SOCS3 and the interaction between SOCS3 and STAT5a. The expression of
      SOCS3 was found in cytoplasm and nucleus of DCMECs by fluorescent immunostaining.
      Overexpression and inhibition of SOCS3 brought a remarkable milk protein
      synthesis change through the regulation of JAK2/STAT5a pathway activity, and
      SOCS3 expression also decreased SREBP-1c expression and fatty acid synthesis.
      Inhibited STAT5a activation correlated with reduced SOCS3 expression, which
      indicated that SOCS3 gene might be one of the targets of STAT5a activation,
      DCMECs treated with L-methionine (Met) resulted in a decrease of SOCS3
      expression. SOCS3 could also decrease cell proliferation and viability by CASY-TT
      detection. Together, our findings indicate that SOCS3 acts as an inhibitor of
      JAK2/STAT5a pathway and disturbs fatty acid synthesis by decreasing SREBP-1c
      expression, which validates its involvement in both milk protein synthesis and
      fat synthesis. In aggregate, these results reveal that low SOCS3 expression is
      required for milk synthesis and proliferation of DCMECs in vitro. 

PMID- 24141251
TI  - A technique for real-time detection, location and quantification of damage in
      large polymer composite structures made of electrically non-conductive fibers and
      carbon nanotube networks.
AB  - In this work, we have developed a novel, practical and real-time structural
      health monitoring (SHM) technique to detect, locate and quantify damage that
      occurs at one or more locations in large polymer composite structures (LPCSs)
      made of electrically non-conductive fibers and carbon nanotube networks. Our
      technique exploits the piezoresistive effect of multiwalled carbon nanotubes
      (MWCNTs) in epoxy resin. The electrically conductive epoxy resin was used to
      prepare glass fiber reinforced composite plates. The plates were marked with grid
      points where electrically conductive silver-epoxy pastes were deposited. The
      electrical resistances between the grid points were measured and used as a
      reference set. Two new concepts are introduced. One is uniformity of MWCNT
      distribution which gives rise to uniformity in electrical conductivity. The
      second is maximum sensitivity to change in electrical resistance due to the
      occurrence of damage. These issues are demonstrated as criteria to determine the
      optimal quantity of MWCNTs. This optimal quantity is used to assure damage
      detectability at any region in the large plates. Drilled holes and impact testing
      were conducted to simulate damage. The damage causes the electrical resistance
      between the contact points surrounding the damage to increase. This increase is
      used to detect, locate and quantify damage. 

PMID- 24141249
TI  - Formation of nanodiamonds at near-ambient conditions via microplasma dissociation
      of ethanol vapour.
AB  - Clusters of diamond-phase carbon, known as nanodiamonds, exhibit novel
      mechanical, optical and biological properties that have elicited interest for a
      wide range of technological applications. Although diamond is predicted to be
      more stable than graphite at the nanoscale, extreme environments are typically
      used to produce nanodiamonds. Here we show that nanodiamonds can be stably formed
      in the gas phase at atmospheric pressure and neutral gas temperatures <100 
      degrees C by dissociation of ethanol vapour in a novel microplasma process.
      Addition of hydrogen gas to the process allows in flight purification by
      selective etching of the non-diamond carbon and stabilization of the
      nanodiamonds. The nanodiamond particles are predominantly between 2 and 5 nm in
      diameter, and exhibit cubic diamond, n-diamond and lonsdaleite crystal
      structures, similar to nanodiamonds recovered from meteoritic residues. These
      results may help explain the origin of nanodiamonds in the cosmos, and offer a
      simple and inexpensive route for the production of high-purity nanodiamonds. 

PMID- 24141250
TI  - Alternative mutational pathways, outside the VPg, of rice yellow mottle virus to
      overcome eIF(iso)4G-mediated rice resistance under strong genetic constraints.
AB  - The adaptation of rice yellow mottle virus (RYMV) to rymv1-mediated resistance
      has been reported to involve mutations in the viral genome-linked protein (VPg).
      In this study, we analysed several cases of rymv1-2 resistance breakdown by an
      isolate with low adaptability. Surprisingly, in these rarely occurring resistance
      breaking (RB) genotypes, mutations were detected outside the VPg, in the
      ORF2a/ORF2b overlapping region. The causal role of three mutations associated
      with rymv1-2 resistance breakdown was validated via directed mutagenesis of an
      infectious clone. In resistant plants, these mutations increased viral
      accumulation as efficiently as suboptimal RB mutations in the VPg. Interestingly,
      these mutations are located in a highly conserved, but unfolded, domain.
      Altogether, our results indicate that under strong genetic constraints, a priori
      unfit genotypes can follow alternative mutational pathways, i.e. outside the VPg,
      to overcome rymv1-2 resistance. 

PMID- 24141252
TI  - Pneumatic dilation and botulinum toxin: when and why?
AB  - Pneumatic dilation and botulinum toxin:when and why? The endoscopic treatment
      options of achalasia include botulinum toxin (BT) injection and pneumatic
      dilation (PD) of the lower esophageal sphincter (LES). BT can reduce the LES
      pressure by blocking the release of acetylcoline from presynaptic cholinergic
      nerve terminals in the myenteric plexus. Although the procedure is safe and good
      initial response is reported, there is a wide variability in the duration of the
      response and the effect tends to decrease over time. BT is usually recommended
      for elderly patients or patients with comorbid illnesses, who are poor candidates
      for more invasive procedures. PD aims at tearing the muscle fibers of the LES and
      is considered the most effective nonsurgical treatment for achalasia. Technical
      details of the procedure vary in different institutions and in many clinical
      settings the choice between PD or minimally invasive surgical myotomy depends
      upon local expertise in the procedures. Further endoscopic treatment options such
      as submucosal esophageal myotomy or self-expanding metallic stents are being
      studied.

PMID- 24141253
TI  - REFINE (REducing Falls in In-patieNt Elderly) using bed and bedside chair
      pressure sensors linked to radio-pagers in acute hospital care: a randomised
      controlled trial.
AB  - BACKGROUND: falls in hospitals are a major problem and contribute to substantial
      healthcare burden. Advances in sensor technology afford innovative approaches to
      reducing falls in acute hospital care. However, whether these are clinically
      effective and cost effective in the UK setting has not been evaluated. METHODS:
      pragmatic, parallel-arm, individual randomised controlled trial of bed and
      bedside chair pressure sensors using radio-pagers (intervention group) compared
      with standard care (control group) in elderly patients admitted to acute, general
      medical wards, in a large UK teaching hospital. Primary outcome measure number of
      in-patient bedside falls per 1,000 bed days. RESULTS: 1,839 participants were
      randomised (918 to the intervention group and 921 to the control group). There
      were 85 bedside falls (65 fallers) in the intervention group, falls rate 8.71 per
      1,000 bed days compared with 83 bedside falls (64 fallers) in the control group,
      falls rate 9.84 per 1,000 bed days (adjusted incidence rate ratio, 0.90; 95%
      confidence interval [CI], 0.66-1.22; P = 0.51). There was no significant
      difference between the two groups with respect to time to first bedside fall
      (adjusted hazard ratio (HR), 0.95; 95% CI: 0.67-1.34; P= 0.12). The mean cost per
      patient in the intervention group was L7199 compared with L6400 in the control
      group, mean difference in QALYs per patient, 0.0001 (95% CI: -0.0006-0.0004, P=
      0.67). CONCLUSIONS: bed and bedside chair pressure sensors as a single
      intervention strategy do not reduce in-patient bedside falls, time to first
      bedside fall and are not cost-effective in elderly patients in acute, general
      medical wards in the UK. TRIAL REGISTRATION: isrctn.org identifier:
      ISRCTN44972300.

PMID- 24141254
TI  - Assessing intermediate coronary lesions: more than meets the eye.

PMID- 24141255
TI  - Disturbed coronary hemodynamics in vessels with intermediate stenoses evaluated
      with fractional flow reserve: a combined analysis of epicardial and
      microcirculatory involvement in ischemic heart disease.
AB  - BACKGROUND: In chronic ischemic heart disease, focal stenosis, diffuse
      atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to
      limit myocardial flow. The prevalence of these ischemic heart disease levels in
      fractional flow reserve (FFR) interrogated vessels remains largely unknown.
      METHODS AND RESULTS: Using intracoronary measurements, 91 coronaries (78
      patients) with intermediate stenoses were classified in 4 FFR and coronary flow
      reserve (CFR) agreement groups, using FFR>0.80 and CFR<2 as cutoffs. Index of
      microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were
      also assessed. MCD was assumed when IMR>=29.1 (75(th) percentile). Fifty-four
      (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal
      CFR and IMR. Among vessels with FFR>0.80, most (63%) presented disturbed
      hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80
      presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4-31.8)]
      than those with FFR<=0.80 [17.3 (95% confidence interval, 13.0-21.7), p=0.001].
      Atherosclerotic burden was inversely correlated with CFR (r=-0.207, P=0.055), and
      in vessels with FFR>0.80 and CFR<2 (n=28, 39%), IMR had a wide dispersion (7-72.7
      U), suggesting a combination of diffuse atherosclerotic narrowings and MCD.
      Vessels with FFR<=0.80 and normal CFR presented the lowest IMR, suggesting a
      preserved microcirculation. CONCLUSIONS: A substantial number of coronary
      arteries with stenoses showing an FFR>0.80 present disturbed hemodynamics.
      Integration of FFR, CFR, and IMR supports the existence of differentiated
      patterns of ischemic heart disease that combine focal and diffuse coronary
      narrowings with variable degrees of MCD.

PMID- 24141257
TI  - Heart factory or fiction?: cardiac progenitor cells and regeneration.

PMID- 24141258
TI  - Impact of toxicological properties of sulfonamides on the growth of zebrafish
      embryos in the water.
AB  - Extensive use of pharmaceutical compounds may result in contamination of water
      bodies lying adjacent to areas where there is a high level of human activity. To
      evaluate potential risks to fish embryos, three sulfonamides were investigated,
      by means of an extended zebrafish (Danio rerio) toxicity test. The bio-toxicity
      of antibacterial sulfonamides, at low concentrations, was investigated by
      observing lethal and sub-lethal effects on embryos and larvae. Results indicated
      that sulfonamides caused obvious toxic effects on spontaneous movements,
      heartbeats and hatching of t embryos, and also resulted in malformations in
      embryos and larvae. A significant toxicity effect was observed in zebrafish
      embryos and larvae that had been exposed to a low concentration of sulfadimidine
      (0.001 mg/L), and a significant difference was noted between the exposed and the
      blank control groups. Exposure to a low concentration of sulfonamide resulted in
      characteristic malformations, including pericardial edema, yolk sac edema,
      hemoglutinations, tail deformation and swim bladder defects.

PMID- 24141259
TI  - Presence of human enteric viruses in the stools of healthy Malawian 6-month-old
      infants.
AB  - The acquisition of intestinal microbiota is essential for infants who are also in
      close contact with intestinal viruses. We assayed the presence of human enteric
      viruses in the faeces of 44 healthy breast-fed 6-month-old infants from rural
      Malawi. Half of the infants tested harboured enteroviruses, although the infants
      had no gastric symptoms, suggesting a viral community mainly composed of human
      asymptomatic enteroviruses. 

PMID- 24141256
TI  - Age-associated defects in EphA2 signaling impair the migration of human cardiac
      progenitor cells.
AB  - BACKGROUND: Aging negatively impacts on the function of resident human cardiac
      progenitor cells (hCPCs). Effective regeneration of the injured heart requires
      mobilization of hCPCs to the sites of damage. In the young heart, signaling by
      the guidance receptor EphA2 in response to the ephrin A1 ligand promotes hCPC
      motility and improves cardiac recovery after infarction. METHODS AND RESULTS: We
      report that old hCPCs are characterized by cell-autonomous inhibition of their
      migratory ability ex vivo and impaired translocation in vivo in the damaged
      heart. EphA2 expression was not decreased in old hCPCs; however, the elevated
      level of reactive oxygen species in aged cells induced post-translational
      modifications of the EphA2 protein. EphA2 oxidation interfered with ephrin A1
      stimulated receptor auto-phosphorylation, activation of Src family kinases, and
      caveolin-1-mediated internalization of the receptor. Cellular aging altered the
      EphA2 endocytic route, affecting the maturation of EphA2-containing endosomes and
      causing premature signal termination. Overexpression of functionally intact EphA2
      in old hCPCs corrected the defects in endocytosis and downstream signaling,
      enhancing cell motility. Based on the ability of phenotypically young hCPCs to
      respond efficiently to ephrin A1, we developed a novel methodology for the
      prospective isolation of live hCPCs with preserved migratory capacity and growth
      reserve. CONCLUSIONS: Our data demonstrate that the ephrin A1/EphA2 pathway may
      serve as a target to facilitate trafficking of hCPCs in the senescent myocardium.
      Importantly, EphA2 receptor function can be implemented for the selection of
      hCPCs with high therapeutic potential, a clinically relevant strategy that does
      not require genetic manipulation of stem cells.

PMID- 24141260
TI  - Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration
      after neomycin insult.
AB  - The ideal strategy for hair cell regeneration is promoting residual supporting
      cell proliferation followed by induction of hair cell differentiation. In this
      study, cultured neonatal mouse organs of Corti were treated with neomycin to
      eliminate hair cells followed by incubation with recombined adenovirus expressing
      Pax2 and/or Math1. Results showed that overexpression of Pax2 significantly
      promoted proliferation of supporting cells. The number of BrdU+/myosin VIIA+
      cells increased significantly in hair cell pre-existing region two weeks after
      adenovirus infection in Ad-Pax2-IRES-Math1 group compared to Ad-Pax2 and Ad-Math1
      groups. This indicated that cotransfection of Pax2 and Math1 induced supporting
      cells to proliferate and differentiate into hair cells in situ. Most new hair
      cells were labeled by FM1-43 suggesting they acquired certain function. The
      results also suggest that inducing proliferating cells rather than quiescent
      cells to differentiate into hair cells by forced expression of Math1 is feasible
      for mammalian hair cell regeneration.

PMID- 24141262
TI  - Molecular cloning and functional characterization of two divergent 4-coumarate :
      coenzyme A ligases from Kudzu (Pueraria lobata).
AB  - As part of the efforts to understand isoflavonoid metabolism in Pueraria lobata
      at the molecular level, the cDNAs encoding two divergent 4-coumarate : coenzyme A
      ligases (4CLs, designated Pl4CL1 and Pl4CL2, respectively) were isolated from P.
      lobata roots. Sequence analysis revealed that Pl4CL1 had an N-terminal extension
      of twenty-one amino acid residues compared to Pl4CL2. Phylogenetic analysis
      showed that Pl4CL1 and Pl4CL2 fell into angiosperm Class II and Class I,
      respectively. Through in vitro biochemical assays, both Pl4CLs were found to have
      the capacity to utilize 4-coumarate and trans-cinnamate as substrates, while
      neither of them could convert sinapate. Pl4CL2 had a broader substrate
      specificity than Pl4CL1. The affinity of Pl4CL1 for 4-coumarate was 2.6-fold
      higher than that of Pl4CL2 (with the Km values of 3.5 uM and 9.1 uM,
      respectively). Combining the dataset including gene expression profiles,
      metabolites measurements, and biochemical properties, our results indicated that
      Pl4CL1, just as other angiosperm Class II 4CLs, might play a role in isoflavone
      biosynthesis in P. lobata, while Pl4CL2 belongs to angiosperm Class I, and may
      function as a housekeeping enzyme concerning lignification. 

PMID- 24141261
TI  - 1-(1,3-Benzodioxol-5-yl-carbo-nyl) piperidine, a modulator of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid receptor, ameliorates exercise
      induced fatigue in mice.
AB  - The current study was designed to investigate the effects of 1-(1,3-benzodioxol-5
      yl-carbonyl) piperidine (1-BCP) on swimming endurance capacity which as one
      indicator of fatigue in the weight-loaded forced swimming mice. Mice were given
      either vehicle or 1-BCP (0.1, or 0.2 mmol/kg body weight daily) by
      intraperitoneal injection once daily for 2 weeks. The 1-BCP groups showed a
      significant increase in swimming time to exhaustion compared with the control
      group. 1-BCP increased the liver glycogen (LG) and muscle glycogen (MG) contents
      significantly, while decreased the lactic acid (LA) and blood urea nitrogen (BUN)
      levels notably compared with control group. Besides, 1-BCP treatment also
      significantly improved the endogenous cellular antioxidant enzymes in mice by
      increasing the activities of superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GSH-Px). Therefore, this study demonstrated for the first
      time that the supplementation of 1-BCP, as a positive allosteric modulator of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, could
      enhance the endurance capacity of mice and facilitated them recovery from
      fatigue. Thus, we provide a new effective therapeutic strategy for fatigue. 

PMID- 24141264
TI  - Total neutron scattering investigation of the structure of a cobalt gallium oxide
      spinel prepared by solvothermal oxidation of gallium metal.
AB  - A new solvothermal synthesis route to mixed-metal gallium oxides with the spinel
      structure has been developed for ternary oxides of ideal composition Ga(3
      x)M(x)O(4-y) (M=Co, Zn, Ni). The structure of the novel cobalt gallate produced
      in this manner, Ga(1.767(8))Co(0.973(8))O(3.752(8)), has been determined from
      total neutron scattering to be a partially defective spinel with mixed-valent
      cobalt (approximately 25% Co(3+) and 75% Co(2+)) and with vacancies on
      approximately 6% of oxygen sites. Pair distribution function (PDF) analysis
      reveals significant local deviations from the average cubic structure, which are
      attributed to the conflicting coordination preferences of the Co(2+) (potential
      Jahn-Teller distortion) and Ga(3+) (Ga off-centring). Reverse Monte Carlo (RMC)
      modelling supports this conclusion since different metal-oxygen bond-distance
      distributions are found for the two cations in the refined configuration. An
      investigation of magnetic properties shows evidence of short-range magnetic order
      and spin-glass-like behaviour, consistent with the structural disorder of the
      material.

PMID- 24141265
TI  - Unravelling the impact of obstacles in diffusion and kinetics of an enzyme
      catalysed reaction.
AB  - Lattice gas automata simulations of diffusion-limited reactions in heterogeneous
      media exhibit fractal-like kinetics, which is a generalised mass action kinetics
      with time-dependent rate constants. We develop a two dimensional lattice gas
      automata simulation of the Michaelis-Menten mechanism in diffusion-limited
      conditions to investigate the effect of density and size of obstacles on reactant
      diffusion and rate coefficients. In order to simulate more physicochemical
      realistic conditions, reactants rotate and interact according to their specific
      orientation. We also model weak interaction forces between reactants and
      obstacles. Our results show that obstacle density and size affect diffusion,
      first- and second-order rates. We also find that particle rotations and weak
      force interactions among particles lead to a significant decay in the fractal
      like kinetic exponent h. These results suggest that the effects of fractal-like
      kinetics disappear under less restricted conditions than previously believed in
      lattice based simulations. 

PMID- 24141263
TI  - In vitro evaluation of inhibitory effect of nuclear factor-kappaB activity by
      small interfering RNA on pro-tumor characteristics of M2-like macrophages.
AB  - Tumor-associated macrophages (TAMs) have an alternatively activated macrophage
      phenotype (M2) and promote cancer cell proliferation, angiogenesis and
      metastasis. Nuclear factor-kappaB (NF-kappaB) is one of the master regulators of
      macrophage polarization. Here, we investigated the effect of inhibition of NF
      kappaB activity by small interfering RNA (siRNA) on the pro-tumor response of
      macrophages located in the tumor microenvironment in vitro. We used mouse
      peritoneal macrophages cultured in conditioned medium from colon-26 cancer cells
      as an in vitro TAM model (M2-like macrophages). Transfection of NF-kappaB (p50)
      siRNA into M2-like macrophages resulted in a significant decrease in the
      secretion of interleukin (IL)-10 (a T helper 2 (Th2) cytokine) and a significant
      increase of T helper 1 (Th1) cytokine production (IL-12, tumor necrosis factor
      alpha, and IL-6). Furthermore, vascular endothelial growth factor production and
      matrix metalloproteinase-9 mRNA expression in M2-like macrophages were suppressed
      by inhibition of NF-kappaB expression with NF-kappaB (p50) siRNA. In addition,
      there was a reduction of arginase mRNA expression and increase in nitric oxide
      production. The cytokine secretion profiles of macrophages cultured in
      conditioned medium from either B16BL6 or PAN-02 cancer cells were also converted
      from M2 to classically activated (M1) macrophages by transfection of NF-kappaB
      (p50) siRNA. These results suggest that inhibition of NF-kappaB activity in M2
      like macrophages alters their phenotype toward M1. 

PMID- 24141266
TI  - Acoustic emission source location using a distributed feedback fiber laser
      rosette.
AB  - This paper proposes an approach for acoustic emission (AE) source localization in
      a large marble stone using distributed feedback (DFB) fiber lasers. The aim of
      this study is to detect damage in structures such as those found in civil
      applications. The directional sensitivity of DFB fiber laser is investigated by
      calculating location coefficient using a method of digital signal analysis. In
      this, autocorrelation is used to extract the location coefficient from the
      periodic AE signal and wavelet packet energy is calculated to get the location
      coefficient of a burst AE source. Normalization is processed to eliminate the
      influence of distance and intensity of AE source. Then a new location algorithm
      based on the location coefficient is presented and tested to determine the
      location of AE source using a Delta (Delta) DFB fiber laser rosette
      configuration. The advantage of the proposed algorithm over the traditional
      methods based on fiber Bragg Grating (FBG) include the capability of: having
      higher strain resolution for AE detection and taking into account two different
      types of AE source for location. 

PMID- 24141268
TI  - Electron correlations in Mn(x)Ga(1-x)A(s)as seen by resonant electron
      spectroscopy and dynamical mean field theory.
AB  - After two decades since the discovery of ferromagnetism in manganese-doped
      gallium arsenide, its origin is still debated, and many doubts are related to the
      electronic structure. Here we report an experimental and theoretical study of the
      valence electron spectrum of manganese-doped gallium arsenide. The experimental
      data are obtained through the differences between off- and on-resonance photo
      emission data. The theoretical spectrum is calculated by means of a combination
      of density-functional theory in the local density approximation and dynamical
      mean field theory, using exact diagonalization as impurity solver. Theory is
      found to accurately reproduce measured data and illustrates the importance of
      correlation effects. Our results demonstrate that the manganese states extend
      over a broad range of energy, including the top of the valence band, and that no
      impurity band splits-off from the valence band edge, whereas the induced holes
      seem located primarily around the manganese impurity. 

PMID- 24141267
TI  - Highly sensitive refractive index sensor based on adiabatically tapered
      microfiber long period gratings.
AB  - We demonstrate a refractive index sensor based on a long period grating (LPG)
      inscribed in a special photosensitive microfiber with double-clad profile. The
      fiber is tapered gradually enough to ensure the adiabaticity of the fiber taper.
      In other words, the resulting insertion loss is sufficiently small. The boron and
      germanium co-doped inner cladding makes it suitable for inscribing gratings into
      its tapered form. The manner of wavelength shift for refractive indices (RIs)
      differs from conventional LPG, and the refractive index detection limit is 1.67 *
      10-5.

PMID- 24141269
TI  - Low-voltage and high-performance buzzer-scanner based streamlined atomic force
      microscope system.
AB  - In this paper we present a novel scanner design in a quad-rod actuation
      structure, actuated by piezoelectric disk buzzers, and a new type of atomic force
      microscope (AFM), which uses this buzzer-scanner and a compact disk/digital
      versatile-disk astigmatic optical pickup unit (OPU) for the detection of
      cantilever movements. Commercially available piezoelectric disk buzzers have a
      low capacitance and can be driven by low-voltage signal sources, such as analog
      outputs from a data acquisition card, without additional voltage or current
      amplifiers. Various scanning ranges can be realized through changing the
      dimensions of the actuation structure and/or the choice of disk buzzer. We
      constructed a buzzer-scanner and evaluated its performance. The scanner had a
      scanning range of 15 MUm in the X and Y directions and an actuation range of 3.5
      MUm on the Z axis, with nonlinearity of 2.11%, 2.73%, and 2.19% for the X,Y and Z
      axes, respectively. The scanner had a resonance frequency of approximately 360 Hz
      on the X and Y axes, and 4.12 kHz on the Z axis. An OPU-AFM with this buzzer
      scanner can resolve single atomic steps of a graphite substrate with a noise
      level of 0.06 nm. The obtained topographic images exhibit much less distortion
      than those obtained with an AFM using a piezoelectric tube scanner. 

PMID- 24141270
TI  - Occurrence of Legionella pneumophila in lakes serving as a cooling system of a
      power plant.
AB  - This study was aimed at determining whether Legionella pneumophila can be found
      in lakes serving as a natural cooling system of a power plant. Water samples were
      collected from five lakes forming the cooling system of the power plants Patnow
      and Konin (Poland). The numbers of bacteria belonging to different phylogenetic
      groups (bacteria, Legionella sp. and L. pneumophila) were determined with the use
      of a molecular FISH method. The results of the present study show that thermally
      altered aquatic environments provide perfect conditions for the growth of L.
      pneumophila. These microorganisms were identified in the biofilm throughout the
      entire research period, and in the subsurface water layer in July and August. The
      percentage of L. pneumophila species in the Legionella genus was 11.55-12.42%. 

PMID- 24141272
TI  - Do oral steroids aid recovery in children with Bell's palsy?
AB  - There is growing evidence that steroids are not beneficial for treatment of
      paediatric patients with Bell's palsy. To investigate, we conducted a
      retrospective longitudinal study examining notes of 100 children, over 12 years
      coded for facial nerve palsy. Of the 79 diagnosed with Bell's palsy, all
      recovered, and for 46 patients we had data on interval from onset of symptoms to
      resolution (median duration in treated group = 5 weeks, range = 39; median
      duration in untreated group = 6 weeks, range = 11; P = .86). From our results, we
      conclude that all children with Bell's palsy recovered, with or without steroid
      treatment, with no statistically significant difference in symptoms duration.
      Complications of unresolved Bell's palsy can have important long-term functional
      and psychosocial consequences. Therefore, we need further research on use of
      steroids in children with complete/severe cases; it would be a shame to omit
      treatment due to "absence of evidence" rather than "evidence of absence." 

PMID- 24141271
TI  - Assessing bioenergetic compromise in autism spectrum disorder with 31P magnetic
      resonance spectroscopy: preliminary report.
AB  - We sought to examine, via Phosphorus-31 magnetic resonance spectroscopy ((31)P
      MRS) in a case-control design, whether bioenergetic deficits in autism spectrum
      disorders extend to the brain and muscle. Six cases with autism spectrum disorder
      with suspected mitochondrial dysfunction (age 6-18 years) and 6 age/sex-matched
      controls underwent (31)P magnetic resonance spectroscopy. The outcomes of focus
      were muscle resting phosphocreatine and intracellular pH as well as postexercise
      phosphocreatine recovery time constant and frontal brain phosphocreatine.
      Intracellular muscle pH was lower in each autism spectrum disorder case than
      their matched control (6/6, P = .03; P = .0048, paired t test). Muscle
      phosphocreatine (5/6), brain phosphocreatine (3/4), and muscle phosphocreatine
      recovery time constant (3/3) trends were in the predicted direction (not all
      participants completed each). This study introduces (31)P magnetic resonance
      spectroscopy as a noninvasive tool for assessment of mitochondrial function in
      autism spectrum disorder enabling bioenergetic assessment in brain and provides
      preliminary evidence suggesting that bioenergetic defects in cases with autism
      spectrum disorder are present in muscle and may extend to brain. 

PMID- 24141273
TI  - Poor wound healing after pial synangiosis in 2 children with moyamoya
      vasculopathy associated with neurofibromatosis type 1.
AB  - Wound healing is a key component of recovery for children with neurologic
      conditions undergoing neurosurgical procedures. Understanding factors that can
      impair wound healing aids in planning long-term clinical care. Children with
      neurofibromatosis type 1 are at risk for vasculopathies in the brain (including
      moyamoya vasculopathy) and in other organs, including the heart, lung, and skin.
      Neurofibromatosis 1 is caused by mutations in the gene for neurofibromin, a
      protein that plays a role in tissue maintenance and repair as well as tumor
      suppression. The authors report 2 children with neurofibromatosis 1-associated
      moyamoya vasculopathy who developed significant wound healing complications after
      pial synangiosis surgery. They discuss possible contributors to these
      complications, including the role of neurofibromin and the possibility of
      vasculopathy affecting the skin, and the implications of poor wound healing in
      pediatric neurology patients. 

PMID- 24141274
TI  - Subacute sclerosing panencephalitis presenting as schizophrenia with an alpha
      coma pattern in a child.
AB  - Subacute sclerosing panencephalitis, a progressive neurodegenerative disorder of
      the central nervous system, can present atypically with uncharacteristic
      electroencephalographic (EEG) features at its onset albeit typically with
      progressive mental deterioration, behavioral changes, and myoclonic jerks. An
      atypical presentation of subacute sclerosing panencephalitis can lead to a delay
      in diagnosis, thus hindering early treatment. Herein, we describe a 14-year-old
      girl who presented with insomnia, amnesia, auditory and visual hallucinations.
      The patient's electroencephalography on admission showed an alpha coma pattern.
      In spite of antipsychiatric treatment (olanzapine 20 mg/d) for 3 months, a
      progressive deterioration in neurologic function was observed. Subacute
      sclerosing panencephalitis was suspected and diagnosis was confirmed by increased
      titers of measles antibodies in the cerebrospinal fluid. The attention of
      pediatricians should be drawn to psychiatric symptoms as possible initial
      presentations of subacute sclerosing panencephalitis in order to avoid needless
      diagnostic and treatment procedures. 

PMID- 24141275
TI  - Health-related quality of life and its relation to disease severity in boys with
      Duchenne muscular dystrophy: satisfied boys, worrying parents--a case-control
      study.
AB  - The progression of Duchenne muscular dystrophy is expected to negatively
      influence the patients' health-related quality of life, but knowledge of the
      relationship with disease severity is limited. We investigated the relationship
      between health-related quality of life (KIDSCREEN-52 questionnaire) and disease
      severity (clinical assessments of body functions and activities) in 40 boys with
      Duchenne muscular dystrophy (19 ambulant, 21 wheelchair dependent) who were in
      different phases of the disease and underwent life-limiting events such as the
      loss of the ability to ambulate and the ability to lift the arms. In addition, we
      compared boys' health-related quality of life perceptions with that of their
      parents. The participants' health-related quality of life was similar to healthy
      peers' and not influenced by disease severity, except for the physical domain.
      Parents scored much lower than the boys on the KIDSCREEN-52 domains Self
      Perception, Moods and Emotions, and Bullying. The latter finding needs attention
      in the management of Duchenne muscular dystrophy. 

PMID- 24141277
TI  - Role of collagen and inorganic components in electrical polarizability of bone.
AB  - Hydroxyapatite (HA) has polarization capability and is able to accumulate
      electrical storage in bone. Experiments were conducted to measure the
      polarization capability of rabbit femurs. After preparing and polarizing bone
      samples using 2% KOH treatment (denoted 2% koh), 2% KOH and baking (2% koh+bake)
      and decalcification (decalcification) as well as untreated bone (untreated),
      stored charges were quantitatively determined using thermally stimulated
      depolarization current (TSDC) measurements. In TSDC spectra, untreated and 2% koh
      samples showed peaks at 100 and 500 degrees C, while 2% koh+bake showed one peak
      at 580 degrees C and decalcification one peak around 100 degrees C. These
      evidences indicated that collagen and inorganic components play a major role in
      polarization of the bone at different temperature conditions.

PMID- 24141276
TI  - Detection of an atypical teratoid rhabdoid brain tumor gene deletion in
      circulating blood using next-generation sequencing.
AB  - Circulating biomarkers such as somatic chromosome mutations are novel diagnostic
      tools to detect cancer noninvasively. We describe focal deletions found in a
      patient with atypical teratoid rhabdoid tumor, a highly aggressive early
      childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and
      histopathology to study the tumor anatomy. Next, we used whole genome sequencing
      (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence
      of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in
      patient's blood also. About 20% of the blood DNA sequencing reads matched the
      tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA
      aberrations are a promising biomarker for atypical teratoid rhabdoid tumor
      patients. The high percentage of tumor DNA detected in blood indicates that
      either circulating brain tumor cells lyse in the blood or that contents of brain
      tumor cells traverse a possibly compromised blood-brain barrier in this patient. 

PMID- 24141278
TI  - Isolation of maedi/visna virus from a sheep in Japan.
AB  - Maedi/visna (MV) is a lentiviral disease of sheep caused by the maedi/visna virus
      (MVV). Although MV is prevalent in many countries, it had not been reported in
      Japan. In 2011, however, three sheep in northern Japan were reported to be
      seropositive against the MVV antigen, indicating a persistent MVV infection. In
      the present study, we isolated MVV from one sheep to confirm MVV infection and
      conducted genomic classification of the virus. The co-culture of leukocytes from
      a seropositive sheep with fetal goat lung cells resulted in the formation of
      syncytial cells and the amplification of a long terminal repeat sequence of MVV
      by polymerase chain reaction. The isolate was confirmed as being MVV, rather than
      the caprine arthritis-encephalitis virus based on phylogenetic analysis of the
      gag gene sequence. Although the sheep was asymptomatic, nonpurulent meningitis
      and demyelination were found in the spinal cord. These were considered to be
      early lesions associated with pathogenic MVV infection. Therefore, the present
      study demonstrated that MVV is distributed in Japan.

PMID- 24141280
TI  - Photophysical processes in single molecule organic fluorescent probes.
AB  - The use of organic fluorescent probes in biochemical and biophysical applications
      of single molecule spectroscopy and fluorescence microscopy techniques continues
      to increase. As single molecule measurements become more quantitative and new
      developments in super-resolution imaging allow researchers to image biological
      materials with unprecedented resolution, it is becoming increasingly important to
      understand how the properties of the probes influence the signals measured in
      these experiments. In this review, we focus on the photochemical and
      photophysical processes of organic fluorophores that affect the properties of
      fluorescence emission. This includes photobleaching, quenching, and the formation
      of non-emissive (dark) states that result in fluorescence blinking in a variety
      of timescales. These processes, if overlooked, can result in an erroneous
      interpretation of the data. Understanding their physical origins, on the other
      hand, allows researchers to design experiments and interpret results so that the
      maximum amount of information about the system of interest can be extracted from
      fluorescence signals. 

PMID- 24141279
TI  - The calibrated laparoscopic Heller myotomy with fundoplication.
AB  - BACKGROUND: Esophageal achalasia is the most common primary esophageal motor
      disorder. Laparoscopic Heller's myotomy combined with fundoplication represents
      the treatment of choice for this disease, achieving good results in about 90% of
      patients. However, about 10% of treated patients refer persistent or recurrent
      dysphagia. Many Authors showed that this failure rate is related to inadequate
      myotomy. OBJECTIVE: To verify, from experimental to clinical study, the
      modifications induced by Heller's myotomy of the esophago- gastric junction on
      LES pressure (LES-P profile, using a computerized manometric system. METHODS:
      From 2002 to 2010 105 patients with achalasia underwent laparoscopic calibrated
      Heller myotomy followed by antireflux surgery. The calibrated Heller myotomy was
      extended for at least 2.5 cm on the esophagus and for 3 cm on the gastric side.
      Each step was evaluated by intraoperative manometry. Moreover, intraoperative
      manometry and endoscopy were used to calibrate the fundoplication. RESULTS: The
      preoperative mean LES-P was 37.73 +/- 12.21. After esophageal and gastric myotomy
      the mean pressure drop was 21.3% and 91.9%, respectively. No mortality was
      reported. CONCLUSION: Laparoscopic calibrated Heller myotomy with fundoplication
      achieves a good outcome in the surgical treatment of achalasia. The use of
      intraoperative manometry enables an adequate calibration of myotomy, being
      effective in the evaluation of the complete pressure drop, avoiding too long
      esophageal myotomy and, especially, too short gastric myotomy, that may be the
      cause of surgical failure.

PMID- 24141281
TI  - The structure of water in solutions containing di- and trivalent cations by
      empirical potential structure refinement.
AB  - Empirical potential structure refinement (EPSR) has been used to build
      experimentally consistent models of a range of electrolyte solutions containing
      di- and trivalent cations: Cu(ClO4)2 at concentrations of 0.5 and 2.0 m, and
      Cr(NO3)3, YCl3 and LaCl3 at a concentration of 1.0 m. The resulting models are
      used to investigate the perturbation of these electrolytes on the pair
      distribution and triplet angle correlations between solvent water molecules,
      compared with those found in the pure solvent. The results elucidate the
      differences that derive from the reflected range of highly structured local
      cation environments and provide a complementary viewpoint on the hydration shell
      geometries.

PMID- 24141282
TI  - Photoinduced luminescent carbon nanostructures with ultra-broadly tailored size
      ranges.
AB  - Carbon nanoparticles (CNPs), hollow CNPs, nanodiamonds, and hybrid graphene
      spheres (HGSPs) are produced by using fs laser ablation in solution. These carbon
      nanostructures emit tunable photoluminescence and two-photon luminescence. The
      photoinduced layer-by-layer assembly of graphene nanosheets is observed to form
      HGSPs with tailored broadly-ranged sizes for the first time. 

PMID- 24141286
TI  - Relative contributions of quantum and double layer capacitance to the
      supercapacitor performance of carbon nanotubes in an ionic liquid.
AB  - Motivated by promising demonstrations of carbon nanotube (CNT) electrodes in
      supercapacitors, we evaluate the capacitive performance of a (6,6) CNT in
      [BMIM][PF6] ionic liquid (IL), with particular attention to the relative
      contributions of the electric double layer (EDL) capacitance (CD) at the CNT/IL
      interface and the quantum capacitance (CQ) of the CNT. Our classical molecular
      dynamics simulations reveal that the use of the CNT improves CD when compared to
      planar graphene, which we discuss in terms of how the electrode curvature affects
      both the electric field strength and IL packing density. In addition, according
      to density functional theory calculations, the CQ of the CNT is constant and
      significantly larger than that of graphene near the Fermi level, which is a
      consequence of the larger number of available electron states in the CNT. Our
      study also shows that the relative performance of the CNT- and graphene-based
      electrodes can be a strong function of applied voltage, which we attribute to the
      shifting contributions of CQ and CD. 

PMID- 24141283
TI  - Early adipogenesis is regulated through USP7-mediated deubiquitination of the
      histone acetyltransferase TIP60.
AB  - Transcriptional coregulators, including the acetyltransferase Tip60, have a key
      role in complex cellular processes such as differentiation. Whereas post
      translational modifications have emerged as an important mechanism to regulate
      transcriptional coregulator activity, the identification of the corresponding
      demodifying enzymes has remained elusive. Here we show that the expression of the
      Tip60 protein, which is essential for adipocyte differentiation, is regulated
      through polyubiquitination on multiple residues. USP7, a dominant
      deubiquitinating enzyme in 3T3-L1 adipocytes and mouse adipose tissue,
      deubiquitinates Tip60 both in intact cells and in vitro and increases Tip60
      protein levels. Furthermore, inhibition of USP7 expression and activity decreases
      adipogenesis. Transcriptome analysis reveals several cell cycle genes to be co
      regulated by both Tip60 and USP7. Knockdown of either factor results in impaired
      mitotic clonal expansion, an early step in adipogenesis. These results reveal
      deubiquitination of a transcriptional coregulator to be a key mechanism in the
      regulation of early adipogenesis. 

PMID- 24141285
TI  - Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone
      suppresses SEB-induced lung inflammation.
AB  - Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB),
      can lead to the induction of acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB
      induced inflammation. In the current study we investigated the potential use of
      the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on
      staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB
      activated immune cells with 4-MU led to reduced proliferation, reduced cytokine
      production as well as an increase in apoptosis when compared to untreated cells.
      Treatment of mice with 4-MU led to protection from SEB-induced lung injury.
      Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels,
      reduction in lung permeability, and reduced pro-inflammatory cytokine production.
      Taken together, these results suggest that use of 4-MU to target hyaluronic acid
      production may be an effective treatment for the inflammatory response following
      exposure to SEB. 

PMID- 24141284
TI  - Appraisal of antiophidic potential of marine sponges against Bothrops jararaca
      and Lachesis muta venom.
AB  - Snakebites are a health problem in many countries due to the high incidence of
      such accidents. Antivenom treatment has regularly been used for more than a
      century, however, this does not neutralize tissue damage and may even increase
      the severity and morbidity of accidents. Thus, it has been relevant to search for
      new strategies to improve antiserum therapy, and a variety of molecules from
      natural sources with antiophidian properties have been reported. In this paper,
      we analyzed the ability of ten extracts from marine sponges (Amphimedon viridis,
      Aplysina fulva, Chondrosia collectrix, Desmapsamma anchorata, Dysidea etheria,
      Hymeniacidon heliophila, Mycale angulosa, Petromica citrina, Polymastia
      janeirensis, and Tedania ignis) to inhibit the effects caused by Bothrops
      jararaca and Lachesis muta venom. All sponge extracts inhibited proteolysis and
      hemolysis induced by both snake venoms, except H. heliophila, which failed to
      inhibit any biological activity. P. citrina inhibited lethality, hemorrhage,
      plasma clotting, and hemolysis induced by B. jararaca or L. muta. Moreover, other
      sponges inhibited hemorrhage induced only by B. jararaca. We conclude that
      Brazilian sponges may be a useful aid in the treatment of snakebites caused by L.
      muta and B. jararaca and therefore have potential for the discovery of molecules
      with antiophidian properties. 

PMID- 24141287
TI  - Reactive oxygen species production in mitochondria of human gingival fibroblast
      induced by blue light irradiation.
AB  - In recent years, it has become well known that the production of reactive oxygen
      species (ROS) induced by blue-light irradiation causes adverse effects of photo
      aging, such as age-related macular degeneration of the retina. Thus, orange
      tinted glasses are used to protect the retina during dental treatment involving
      blue-light irradiation (e.g., dental resin restorations or tooth bleaching
      treatments). However, there are few studies examining the effects of blue-light
      irradiation on oral tissue. For the first time, we report that blue-light
      irradiation by quartz tungsten halogen lamp (QTH) or light-emitting diode (LED)
      decreased cell proliferation activity of human gingival fibroblasts (HGFs) in a
      time-dependent manner (<5 min). Additionally, in a morphological study, the
      cytotoxic effect was observed in the cell organelles, especially the
      mitochondria. Furthermore, ROS generation induced by the blue-light irradiation
      was detected in mitochondria of HGFs using fluorimetry. In all analyses, the
      cytotoxicity was significantly higher after LED irradiation compared with
      cytotoxicity after QTH irradiation. These results suggest that blue light
      irradiation, especially by LED light sources used in dental aesthetic treatment,
      might have adverse effects on human gingival tissue. Hence, this necessitates the
      development of new dental aesthetic treatment methods and/or techniques to
      protect HGFs from blue light irradiation during dental therapy.

PMID- 24141288
TI  - Attributes characterizing spontaneous ultra-weak photon signals of human
      subjects.
AB  - Sixty visible range photon signals spontaneously emitted from the dorsal side of
      both hands of fifteen human subjects are analyzed with the aim of finding their
      attributes. The signals are of 30 min duration and detected in bins of 50 ms by
      two synchronized photo multipliers sensitive in the range (290-630 nm). Each
      signal is a time series of 36,000 elements. The attributes of its signal are
      determined from the statistical properties of time series. The mean and variance
      of time series determine the attributes signal strength and intercept (p0) and
      slope (p1) of the Fano Factor curve. The photon count distribution of the time
      series determines squeezed state parameters |alpha|, r, theta and phi, squeezed
      state index (SSI), and sum of the squares of residue (SSR). The correlation
      between simultaneously detected signals determines intercept (c0) and slope (c1)
      of their correlation curve. The variability of attributes is studied by
      calculating them in smaller intervals covering the entire signal. The profile of
      attribute at 12 sites in a subject is more informative and biologically relevant.

PMID- 24141290
TI  - From classroom to bedside: integration of the basic science curriculum in medical
      teaching.

PMID- 24141289
TI  - Mechanistic understanding of surface plasmon assisted catalysis on a single
      particle: cyclic redox of 4-aminothiophenol.
AB  - Surface plasmon assisted catalysis (SPAC) reactions of 4-aminothiophenol (4ATP)
      to and back from 4,4'-dimercaptoazobenzene (DMAB) have been investigated by
      single particle surface enhanced Raman spectroscopy, using a self-designed gas
      flow cell to control the reductive/oxidative environment over the reactions.
      Conversion of 4ATP into DMAB is induced by energy transfer (plasmonic heating)
      from surface plasmon resonance to 4ATP, where O2 (as an electron acceptor) is
      essential and H2O (as a base) can accelerate the reaction. In contrast, hot
      electron (from surface plasmon decay) induction drives the reverse reaction of
      DMAB to 4ATP, where H2O (or H2) acts as the hydrogen source. More interestingly,
      the cyclic redox between 4ATP and DMAB by SPAC approach has been demonstrated.
      This SPAC methodology presents a unique platform for studying chemical reactions
      that are not possible under standard synthetic conditions.

PMID- 24141291
TI  - Clustering and combining pattern of metabolic syndrome components in a rural
      Brazilian adult population.
AB  - CONTEXT AND OBJECTIVE Metabolic syndrome is characterized by clustering of
      cardiovascular risk factors such as obesity, dyslipidemia, insulin resistance,
      hyperinsulinemia, glucose intolerance and arterial hypertension. The aim of this
      study was to estimate the probability of clustering and the combination pattern
      of three or more metabolic syndrome components in a rural Brazilian adult
      population. DESIGN AND SETTING This was a cross-sectional study conducted in two
      rural communities located in the Jequitinhonha Valley, Minas Gerais, Brazil.
      METHODS The sample was composed of 534 adults (both sexes). Waist circumference,
      blood pressure and demographic, lifestyle and biochemical characteristics were
      assessed. The prevalences of metabolic syndrome and its components were estimated
      using the definitions of the National Cholesterol Education Program - Adult
      Treatment Panel III. A binomial distribution equation was used to evaluate the
      probability of clustering of metabolic syndrome components. The statistical
      significance level was set at 5% (P < 0.05). RESULTS Metabolic syndrome was more
      frequent among women (23.3%) than among men (6.5%). Clustering of three or more
      metabolic syndrome components was greater than expected by chance. The commonest
      combinations of three metabolic syndrome components were: hypertriglyceridemia +
      low levels of HDL-c + arterial hypertension and abdominal obesity + low levels of
      HDL-c + arterial hypertension; and of four metabolic syndrome components:
      abdominal obesity + hypertriglyceridemia + low levels of HDL-c + arterial
      hypertension. CONCLUSION The population studied presented high prevalence of
      metabolic syndrome among women and clustering of its components greater than
      expected by chance, suggesting that the combination pattern was non-random. 

PMID- 24141292
TI  - Obstructive sleep apnea syndrome: complaints and housing characteristics in a
      population in the United States.
AB  - CONTEXT AND OBJECTIVE Obstructive sleep apnea syndrome (OSAS) is one of the
      leading causes of morbidity and mortality in adults. Early detection of the
      disorder and discovery of risk factors through standardized questionnaires will
      lead to reduction of the OSAS burden. The main aim of this study was to estimate
      the prevalence of OSAS symptoms and examine their association with housing
      characteristics. DESIGN AND SETTING Cross-sectional study at a medical school.
      METHODS Demographic, housing and body measurement data on 5,545 individuals aged
      16 years and over of various races were selected from the National Health and
      Nutrition Examination Survey. We analyzed the probability of OSAS based on
      habitual snoring combined with daytime sleepiness and/or witnessed apnea.
      Univariate and multiple linear regression were used. RESULTS 9.8% of the men and
      6.9% of the women reported symptoms suggestive of OSAS (habitual snoring, daytime
      sleepiness and/or apnea). The following prevalences of symptoms were found among
      males and females respectively: frequent snoring 35.1%, 22.3%, excessive daytime
      sleepiness 6.4%, 3.4% and frequent apnea 14.9%, 20.6%. Using multiple linear
      regression, OSAS symptoms were correlated with gender, age, body mass index
      (BMI), marital status and education. Regarding housing characteristics, mildew or
      musty smell and pets in the environment were associated with a high probability
      of OSAS. CONCLUSION OSAS symptoms were more prevalent than in developing
      countries. The environment was an important risk factor, but environmental
      factors are easier to control and manage than other variables like BMI or
      socioeconomic status. 

PMID- 24141295
TI  - Translation, cross-cultural adaptation and validation of the Brazilian version of
      the Nonarthritic Hip Score.
AB  - CONTEXT AND OBJECTIVE The Nonarthritic Hip Score (NAHS) is a clinical evaluation
      questionnaire that was developed in the English language to evaluate hip function
      in young and physically active patients. The aims of this study were to translate
      this questionnaire into the Brazilian Portuguese language, to adapt it to
      Brazilian culture and to validate it. DESIGN AND SETTING Cohort study conducted
      between 2008 and 2010, at Universidade do Estado do Rio de Janeiro (UERJ).
      METHODS Questions about physical activities and household chores were modified to
      better fit Brazilian culture. Reproducibility, internal consistency and validity
      (correlations with the Algofunctional Lequesne Index and the Western Ontario and
      McMaster Universities Arthritis Index [WOMAC]) were tested. The NAHS-Brazil,
      Lequesne and WOMAC questionnaires were applied to 64 young and physically active
      patients (mean age, 40.9 years; 31 women). RESULTS The intraclass correlation
      coefficient (which measures reproducibility) was 0.837 (P < 0.001). Bland-Altman
      plots revealed a mean error in the difference between the two measurements of
      0.42. The internal consistency was confirmed through a Cronbach alpha of 0.944.
      The validity between NAHS-Brazil and Lequesne and between NAHS-Brazil and WOMAC
      showed high correlations, r = 0.7340 and r = 0.9073, respectively. NAHS-Brazil
      showed good validity with no floor or ceiling effects. CONCLUSION The NAHS was
      translated into the Brazilian Portuguese language and was cross-culturally
      adapted to Brazilian culture. It was shown to be a useful tool in clinical
      practice for assessing the quality of life of young and physically active
      patients with hip pain. 

PMID- 24141293
TI  - Circumstances and factors associated with accidental deaths among children,
      adolescents and young adults in Cuiaba, Brazil.
AB  - CONTEXT AND OBJECTIVE Analysis on accidents from the perspective of population
      segments shows there is higher incidence among children, adolescents and young
      adults. Since the characteristics and circunstances of the event are closely
      related to educational, economic, social and cultural issues, identifying them
      may contribute towards minimizing the causes, which are often fatal. The aim here
      was to identify the environmental, chemical, biological and cultural factors
      associated with deaths due to accidents among children, adolescents and young
      adults in Cuiaba, in 2009. DESIGN AND SETTING This was a descriptive cross
      sectional study conducted in Cuiaba, Mato Grosso, Brazil. RESULTS Thirty-nine
      accidental deaths of individuals aged 0 to 24 years were examined: 56.4% due to
      traffic accidents; 25.6%, drowning; 10.3%, aspiration of milk; 5.1%, falls; and
      2.6%, accidentally triggering a firearm. Male victims predominated (82.1%). The
      presence of chemical, environmental and biological risk factors was observed in
      almost all of the homes. Regarding cultural factors and habits, a large
      proportion of the families had no idea whether accidents were foreseeable events
      and others did not believe that the family's habits might favor their occurrence.
      Delegation of household chores or care of younger siblings to children under the
      age of 10 was common among the families studied. CONCLUSION The results point
      towards the need to have safe and healthy behavioral patterns and environments,
      and to monitor occurrences of accidents, thereby structuring and consolidating
      the attendance provided for victims. 

PMID- 24141294
TI  - Clinical and hematological effects of hydroxyurea therapy in sickle cell
      patients: a single-center experience in Brazil.
AB  - CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic
      disorder among people of African descent, affecting approximately 3,500 newborns
      each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating
      patients with SCD, thereby reducing morbidity and mortality. The objective was to
      analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING
      Retrospective study conducted at a sickle cell centre in Ribeirao Preto, Sao
      Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients.
      The hematological parameters and clinical events that occurred during the year
      before and the first year of treatment with HU were analyzed. The mean dose of HU
      was 24.5 +/- 5.5 mg/kg/day. RESULTS There were rises in three parameters:
      hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to
      19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and
      reductions in the numbers of leukocytes (10,050/ul to 5,700/ul, P < 0.0001),
      neutrophils (6,200/ul to 3,400/ul, P = 0.001), platelets (459,000/ul to
      373,000/ul, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest
      syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047),
      hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P =
      0.0051). CONCLUSION The patients presented clinical and hematological
      improvements, with an increase in HbF and a reduction in the infection rate,
      which had not been addressed in most previous studies. 

PMID- 24141296
TI  - The IDEAL classification system: a new method for classifying fractures of the
      distal extremity of the radius - description and reproducibility.
AB  - CONTEXT AND OBJECTIVE There is no consensus concerning which classification for
      distal radius fractures is best and the existing methods present poor
      reproducibility. This study aimed to describe and assess the reproducibility of
      the new IDEAL classification, and to compare it with widely used systems. DESIGN
      AND SETTING Reproducibility study, Hand Surgery Section, Universidade Federal de
      Sao Paulo. METHODS The IDEAL classification and its evidence-based rationale are
      presented. Sixty radiographs (posteroanterior and lateral) from patients with
      distal radius fractures were classified by six examiners: a hand surgery
      specialist, a hand surgery resident, an orthopedic generalist, an orthopedic
      resident and two medical students. Each of them independently assessed the
      radiographs at three different times. We compared the intra and interobserver
      concordance of the IDEAL, AO, Frykman and Fernandez classifications using Cohen's
      kappa (kappa) (for two observers) and Fleiss's kappa (for more than two
      observers). RESULTS The concordance was high for the IDEAL classification (kappa
      = 0.771) and moderate for Frykman (kappa = 0.556), Fernandez (kappa = 0.671) and
      AO (kappa = 0.650). The interobserver agreement was moderate for the IDEAL
      classification (kappa = 0.595), but unsatisfactory for Frykman (kappa = 0.344),
      Fernandez (kappa = 0.496) and AO (kappa = 0.343). CONCLUSION The reproducibility
      of the IDEAL classification was better than that of the other systems analyzed,
      thus making the IDEAL system suitable for application. Complementary studies will
      confirm whether this classification system makes adequate predictions for therapy
      and prognosis. 

PMID- 24141297
TI  - Trends in treatment of anterior cruciate ligament injuries of the knee in the
      public and private healthcare systems of Brazil.
AB  - CONTEXT AND OBJECTIVE Orthopedic surgery implies high costs for both public and
      private healthcare. The aim of this study was to better understand the
      differences between the public and private sectors regarding treatment of a
      damaged anterior cruciate ligament, which is a common knee injury. DESIGN AND
      SETTING Descriptive cross-sectional study conducted during the Brazilian
      Orthopedics Congress in Brasilia. METHODS We applied questionnaires during the
      2010 Brazilian Orthopedics Congress, with participation by 241 knee surgeons from
      24 Brazilian states. This was followed by statistical analysis on the data that
      were obtained. RESULTS The orthopedic surgeons who were evaluated used different
      approaches and treatment options in different Brazilian states, comparing between
      the public and private systems. CONCLUSION Both in the public and in the private
      systems in Brazil, because of non-medical issues surrounding the treatment, the
      best medical decision is not always made. This may be harmful both to patients
      and to physicians. 

PMID- 24141298
TI  - Diagnosis and treatment of mast cell disorders: practical recommendations.
AB  - CONTEXT AND OBJECTIVE The term mastocytosis covers a group of rare disorders
      characterized by neoplastic proliferation and accumulation of clonal mast cells
      in one or more organs. The aim of this study was to assess the principal elements
      for diagnosing and treating these disorders. DESIGN AND SETTING Narrative review
      of the literature conducted at Grupo Fleury, Sao Paulo, Brazil. METHODS This
      study reviewed the scientific papers published in the PubMed, Embase (Excerpta
      Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciencias da
      Saude) and Cochrane Library databases that were identified using the search term
      "mastocytosis." RESULTS The clinical presentation of mastocytosis is remarkably
      heterogeneous and ranges from skin lesions that may regress spontaneously to
      aggressive forms associated with organ failure and short survival. Currently,
      seven subtypes of mastocytosis are recognized through the World Health
      Organization classification system for hematopoietic tumors. These disorders are
      diagnosed based on clinical manifestations and on identification of neoplastic
      mast cells using morphological, immunophenotypic, genetic and molecular methods.
      Abnormal mast cells display atypical and frequently spindle-shaped morphology,
      and aberrant expression of the CD25 and CD2 antigens. Elevation of serum tryptase
      is a common finding in some subtypes, and more than 90% of the patients present
      the D816V KIT mutation in mast cells. CONCLUSION Here, we described the most
      common signs and symptoms among patients with mastocytosis and suggested a
      practical approach for the diagnosis, classification and initial clinical
      treatment of mastocytosis. 

PMID- 24141299
TI  - Bilateral tibial hemimelia type 1 (1a and 1b) with T9 and T10 hemivertebrae: a
      novel association.
AB  - CONTEXT Congenital absence of the tibia is a rare anomaly with an incidence of
      one per 1,000,000 live births. It is mostly sporadic and can be identified as an
      isolated disorder or as part of malformation syndromes. CASE REPORT A male child,
      born to unaffected and non-consanguineous parents, presented with shortening of
      the legs and adduction of both feet. Physical examination at six months of age
      showed head circumference of 44.5 cm (75th percentile), length 60 cm (< 3rd
      percentile), weight 7,700 g (50th percentile), shortening of the left thigh and
      both legs with varus foot. There were no craniofacial dysmorphisms or chest,
      abdominal, genital or upper-extremity anomalies. Psychomotor development was
      normal. His workup, including renal and cranial ultrasonography, brainstem
      auditory evoked potential, and ophthalmological and cardiological examinations,
      was normal. X-rays showed bilateral absence of the tibia with intact fibulae,
      distally hypoplastic left femur, and normal right femur. In addition, spinal
      radiographs showed hemivertebrae at T9 and T10. CONCLUSION This novel association
      expands the spectrum of tibial hemimelia. Moreover, this observation highlights
      the usefulness of this inexpensive diagnostic method (X-rays) for characterizing
      the great clinical and radiological variability of tibial hemimelia. 

PMID- 24141300
TI  - Ginseng: potential for the antileishmanial arsenal?

PMID- 24141301
TI  - Medicine and creativity in medical psychology.

PMID- 24141302
TI  - Should every adult patient in the hospital have an internist?

PMID- 24141305
TI  - II-VI nanowire radial heterostructures.
AB  - There are many reports of ZnSe nanowire synthesis, but photoluminescence
      measurements on these nanowires indicate weak band-edge and high sub-bandgap
      defect emission. The two main contributors to the non-optimal photoluminescence
      are nanowire growth at high temperatures and unpassivated surface states. In this
      paper, the synthesis of II-VI core-shell nanowires by metal organic vapor phase
      epitaxy is reported. We demonstrate that larger bandgap shells that passivate the
      nanowire surface states can be deposited around the nanowires by increasing the
      partial pressures of the shell reactants without a large increase in growth
      temperature, allowing high quality material to be obtained. The deposition of
      nearly lattice-matched ZnMgSSe shells on the ZnSe nanowires increases the band
      edge luminescent intensity of the ZnSe nanowires by more than four orders of
      magnitude and improves the band-edge to defect photoluminescence intensity ratio
      to 12,000:1. The corresponding full widths at half maximum of the band-edge
      exciton peaks of the core-shell nanowires can be as narrow as 2.8 nm. It is also
      shown that magnesium and chlorine can be incorporated into the ZnSe nanowire
      cores, which shortens the emission wavelength and is known to act as an n-type
      dopant, respectively.

PMID- 24141306
TI  - The microfluidic Kelvin water dropper.
AB  - The so-called "Kelvin water dropper" is a simple experiment demonstrating the
      spontaneous appearance of induced free charge in droplets emitted through a tube.
      As Lord Kelvin explained, water droplets spontaneously acquire a net charge
      during detachment from a faucet due to the presence of electrical fields in their
      surroundings created by any metallic object. In his experiment, two streams of
      droplets are allowed to drip from separate nozzles into separate buckets, which
      are, at the same time, interconnected through the dripping needles. In this
      paper, we build a microfluidic water dropper and demonstrate that the droplets
      get charged and break up due to electrohydrodynamic instabilities. A comparison
      with recent simulations shows the dependence of the acquired charge in the
      droplets on different parameters of the system. The phenomenon opens a door to
      cheap and accessible transformation of pneumatic pressure into electrical energy
      and to an enhanced control in microfluidic and biophysical manipulation of
      capsules, cells and droplets via self-induced charging of the elements. 

PMID- 24141307
TI  - Fatal familial insomnia (FFI) complicated by posterior reversible encephalopathy
      syndrome (PRES).

PMID- 24141309
TI  - A population of Nestin-expressing progenitors in the cerebellum exhibits
      increased tumorigenicity.
AB  - It is generally believed that cerebellar granule neurons originate exclusively
      from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here
      we identified a rare population of neuronal progenitors in mouse developing
      cerebellum that expresses Nestin. Although Nestin is widely considered a marker
      for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are
      committed to the granule neuron lineage. Unlike conventional GNPs, which reside
      in the outer EGL and proliferate extensively, NEPs reside in the deep part of the
      EGL and are quiescent. Expression profiling revealed that NEPs are distinct from
      GNPs and, in particular, express markedly reduced levels of genes associated with
      DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog
      (Shh) signaling, NEPs exhibited more severe genomic instability and gave rise to
      tumors more efficiently than GNPs. These studies revealed a previously
      unidentified progenitor for cerebellar granule neurons and a cell of origin for
      medulloblastoma. 

PMID- 24141310
TI  - Common medial frontal mechanisms of adaptive control in humans and rodents.
AB  - In this report we describe how common brain networks within the medial frontal
      cortex (MFC) facilitate adaptive behavioral control in rodents and humans. We
      demonstrate that after errors, low-frequency oscillations below 12 Hz are
      modulated over the midfrontal cortex in humans and within the prelimbic and
      anterior cingulate regions of the MFC in rats. These oscillations were phase
      locked between the MFC and motor areas in both rats and humans. In rats, single
      neurons that encoded prior behavioral outcomes were phase coherent with low
      frequency field oscillations, particularly after errors. Inactivating the medial
      frontal regions in rats led to impaired behavioral adjustments after errors,
      eliminated the differential expression of low-frequency oscillations after errors
      and increased low-frequency spike-field coupling within the motor cortex. Our
      results describe a new mechanism for behavioral adaptation through low-frequency
      oscillations and elucidate how medial frontal networks synchronize brain activity
      to guide performance. 

PMID- 24141308
TI  - Nitrate and periplasmic nitrate reductases.
AB  - The nitrate anion is a simple, abundant and relatively stable species, yet plays
      a significant role in global cycling of nitrogen, global climate change, and
      human health. Although it has been known for quite some time that nitrate is an
      important species environmentally, recent studies have identified potential
      medical applications. In this respect the nitrate anion remains an enigmatic
      species that promises to offer exciting science in years to come. Many bacteria
      readily reduce nitrate to nitrite via nitrate reductases. Classified into three
      distinct types--periplasmic nitrate reductase (Nap), respiratory nitrate
      reductase (Nar) and assimilatory nitrate reductase (Nas), they are defined by
      their cellular location, operon organization and active site structure. Of these,
      Nap proteins are the focus of this review. Despite similarities in the catalytic
      and spectroscopic properties Nap from different Proteobacteria are
      phylogenetically distinct. This review has two major sections: in the first
      section, nitrate in the nitrogen cycle and human health, taxonomy of nitrate
      reductases, assimilatory and dissimilatory nitrate reduction, cellular locations
      of nitrate reductases, structural and redox chemistry are discussed. The second
      section focuses on the features of periplasmic nitrate reductase where the
      catalytic subunit of the Nap and its kinetic properties, auxiliary Nap proteins,
      operon structure and phylogenetic relationships are discussed.

PMID- 24141311
TI  - Adaptation in sound localization: from GABA(B) receptor-mediated synaptic
      modulation to perception.
AB  - Across all sensory modalities, the effect of context-dependent neural adaptation
      can be observed at every level, from receptors to perception. Nonetheless, it has
      long been assumed that the processing of interaural time differences, which is
      the primary cue for sound localization, is nonadaptive, as its outputs are mapped
      directly onto a hard-wired representation of space. Here we present evidence
      derived from in vitro and in vivo experiments in gerbils indicating that the
      coincidence-detector neurons in the medial superior olive modulate their
      sensitivity to interaural time differences through a rapid, GABA(B) receptor
      mediated feedback mechanism. We show that this mechanism provides a gain control
      in the form of output normalization, which influences the neuronal population
      code of auditory space. Furthermore, psychophysical tests showed that the
      paradigm used to evoke neuronal GABA(B) receptor-mediated adaptation causes the
      perceptual shift in sound localization in humans that was expected on the basis
      of our physiological results in gerbils.

PMID- 24141312
TI  - Integration of the olfactory code across dendritic claws of single mushroom body
      neurons.
AB  - In the olfactory system, sensory inputs are arranged in different glomerular
      channels, which respond in combinatorial ensembles to the various chemical
      features of an odor. We investigated where and how this combinatorial code is
      read out deeper in the brain. We exploited the unique morphology of neurons in
      the Drosophila mushroom body, which receive input on large dendritic claws.
      Imaging odor responses of these dendritic claws revealed that input channels with
      distinct odor tuning converge on individual mushroom body neurons. We determined
      how these inputs interact to drive the cell to spike threshold using
      intracellular recordings to examine mushroom body responses to optogenetically
      controlled input. Our results provide an elegant explanation for the
      characteristic selectivity of mushroom body neurons: these cells receive
      different types of input and require those inputs to be coactive to spike. These
      results establish the mushroom body as an important site of integration in the
      fly olfactory system. 

PMID- 24141315
TI  - cMET as a potential therapeutic target in gastric cancer (Review).
AB  - Gastric cancer is one of the most common malignancies worldwide. Despite
      improvements in surgery and chemotherapy, the outcomes in patients with advanced
      gastric cancer remain poor. cMET is a member of the receptor tyrosine kinase
      family, and plays a key role in tumor survival, growth, angiogenesis and
      metastasis. cMET overexpression and/or gene amplification occurs in a significant
      proportion of gastric cancers. cMET is associated with a high tumor stage and
      poor prognosis. Several cMET inhibitors have been investigated in clinical
      trials, and the initial results are encouraging. It has become increasingly
      apparent that cMET is a promising therapeutic target in gastric cancer. In this
      review, we summarize the development of cMET inhibitors in the preclinical and
      clinical environment. In addition, we discuss the challenges of cMET-targeted
      therapy in gastric cancer and explore possible solutions. 

PMID- 24141314
TI  - Parallel, multi-stage processing of colors, faces and shapes in macaque inferior
      temporal cortex.
AB  - Visual-object processing culminates in inferior temporal cortex (IT). To assess
      the organization of IT, we measured functional magnetic resonance imaging
      responses in alert monkeys to achromatic images (faces, fruit, bodies and places)
      and colored gratings. IT contained multiple color-biased regions, which were
      typically ventral to face patches and yoked to them, spaced regularly at four
      locations predicted by known anatomy. Color and face selectivity increased for
      more anterior regions, indicative of a broad hierarchical arrangement. Responses
      to non-face shapes were found across IT, but were stronger outside color-biased
      regions and face patches, consistent with multiple parallel streams. IT also
      contained multiple coarse eccentricity maps: face patches overlapped central
      representations, color-biased regions spanned mid-peripheral representations and
      place-biased regions overlapped peripheral representations. These results show
      that IT comprises parallel, multi-stage processing networks subject to one
      organizing principle. 

PMID- 24141313
TI  - Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells
      in vivo.
AB  - Hippocampal sharp waves are population discharges initiated by an unknown
      mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate
      action potential generation through GABAergic synapses on the axon initial
      segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving
      rats stopped firing during sharp waves, when pyramidal cells fire most. AACs
      fired strongly and rhythmically around the peak of theta oscillations, when
      pyramidal cells fire at low probability. Distinguishing AACs from other
      parvalbumin-expressing interneurons by their lack of detectable SATB1
      transcription factor immunoreactivity, we discovered a somatic GABAergic input
      originating from the medial septum that preferentially targets AACs. We recorded
      septo-hippocampal GABAergic cells that were activated during hippocampal sharp
      waves and projected to CA3. We hypothesize that inhibition of AACs, and the
      resulting subcellular redistribution of inhibition from the axon initial segment
      to other pyramidal cell domains, is a necessary condition for the emergence of
      sharp waves promoting memory consolidation. 

PMID- 24141316
TI  - Feasibility study of red blood cell debulking by magnetic field-flow
      fractionation with step-programmed flow.
AB  - Emerging applications of rare cell separation and analysis, such as separation of
      mature red blood cells from hematopoietic cell cultures, require efficient
      methods of red blood cell (RBC) debulking. We have tested the feasibility of
      magnetic RBC separation as an alternative to centrifugal separation using an
      approach based on the mechanism of magnetic field-flow fractionation (MgFFF). A
      specially designed permanent magnet assembly generated a quadrupole field having
      a maximum field of 1.68 T at the magnet pole tips, zero field at the aperture
      axis, and a nearly constant radial field gradient of 1.75 T/mm (with a negligible
      angular component) inside a cylindrical aperture of 1.9 mm (diameter) and 76 mm
      (length). The cell samples included high-spin hemoglobin RBCs obtained by
      chemical conversion of hemoglobin to methemoglobin (met RBC) or by exposure to
      anoxic conditions (deoxy RBC), low-spin hemoglobin obtained by exposure of RBC
      suspension to ambient air (oxy RBC), and mixtures of deoxy RBC and cells from a
      KG-1a white blood cell (WBC) line. The observation that met RBCs did not elute
      from the channel at the lower flow rate of 0.05 mL/min applied for 15 min but
      quickly eluted at the subsequent higher flow rate of 2.0 mL/min was in agreement
      with FFF theory. The well-defined experimental conditions (precise field and flow
      characteristics) and a well-established FFF theory verified by studies with model
      cell systems provided us with a strong basis for making predictions about
      potential practical applications of the magnetic RBC separation. 

PMID- 24141317
TI  - Qualitative metabolism assessment and toxicological detection of xylazine, a
      veterinary tranquilizer and drug of abuse, in rat and human urine using GC-MS, LC
      MSn, and LC-HR-MSn.
AB  - Xylazine is used in veterinary medicine for sedation, anesthesia, and analgesia.
      It has also been reported to be misused as a horse doping agent, a drug of abuse,
      a drug for attempted sexual assault, and as source of accidental or intended
      poisonings. So far, no data concerning human metabolism have been described. Such
      data are necessary for the development of toxicological detection methods for
      monitoring drug abuse, as in most cases the metabolites are the analytical
      targets. Therefore, the metabolism of xylazine was investigated in rat and human
      urine after several sample workup procedures. The metabolites were identified
      using gas chromatography (GC)-mass spectrometry (MS) and liquid chromatography
      (LC) coupled with linear ion trap high-resolution multistage MS (MS(n)). Xylazine
      was N-dealkylated and S-dealkylated, oxidized, and/or hydroxylated to 12 phase I
      metabolites. The phenolic metabolites were partly excreted as glucuronides or
      sulfates. All phase I and phase II metabolites identified in rat urine were also
      detected in human urine. In rat urine after a low dose as well as in human urine
      after an overdose, mainly the hydroxy metabolites were detected using the
      authors' standard urine screening approaches by GC-MS and LC-MS(n). Thus, it
      should be possible to monitor application of xylazine assuming similar
      toxicokinetics in humans.

PMID- 24141318
TI  - Development of exposure assessment method based on the analysis of urinary
      heterocyclic amines as biomarkers by on-line in-tube solid-phase microextraction
      coupled with liquid chromatography-tandem mass spectrometry.
AB  - Heterocyclic amines (HCAs) formed in cooked meats and fish are mutagens and
      carcinogens in rodents and nonprimates. Exposure to HCAs may also be a risk
      factor for human tumors, but the association between dietary intake and human
      cancer risk has not been determined. To assess recent exposure to HCAs, we
      developed a simple and sensitive method for measuring HCAs in urine by automated
      on-line in-tube solid-phase microextraction (SPME) using a Supel-Q PLOT capillary
      column as an extraction device, in combination with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). Thirteen HCAs were separated within 15 min using a
      ZORBAX Eclipse XDB-C8 column and detected selectively by multiple reaction
      monitoring using MS/MS. This method can be applied easily to the analysis of
      small amounts of urine samples without any other pretreatment except for alkaline
      hydrolysis of bound forms of HCAs. The quantification limits of HCAs in 0.2 mL of
      urine samples were about 1.7-4.1 pg/mL (S/N = 10). Using this method, we
      evaluated the exposure to HCAs in persons who consumed well-done pan-fried beef
      and the suitability of using urinary HCAs as exposure biomarkers. We also
      analyzed the ability of vegetable consumption to prevent carcinogenic risks from
      exposure to HCAs by measuring free and bound forms of HCAs in urine.

PMID- 24141319
TI  - Laparotomic approach in "achalasia surgery". Have still a role in minimally
      invasive laparoscopic surgery era?
AB  - Laparotomy can be considered as an access route among options that any oesophagus
      surgeon has to include in his technical experience. It can therefore either be
      chosen when the right indication emerges or be suggested as first line-procedure
      by the surgeon when he is sure that it can guarantee the best possible outcomes.
      Outcome that, in the Author's experience, show the surgical procedure Heller's
      extramuscular myotomy with anterior hemifundoplication according to Dor a well
      documented procedure the safety and effectiveness of wich has been upgraded over
      time through new technical devices. Their effectiveness being equal, both
      techniques are widely acceptable and opting for one approach or the other depends
      on the expertise of the single surgeon who has to consider all the possible
      advantages for his patients.

PMID- 24141320
TI  - Developing an indirect ELISA based on recombinant hexon protein for serological
      detection of inclusion body hepatitis in chickens.
AB  - Fowl adenovirus (FAdv) serotype 2 causes inclusion body hepatitis (IBH) disease
      which adversely affects the broiler industry in Thailand. We developed an
      indirect ELISA based on the recombinant hexon protein produced by E. coli. The
      recombinant hexon protein was tested with sera, in both infected and noninfected
      chickens. The recombinant hexon protein was standardized with an antigen
      concentration of 3.75 ug/ml and test sera. The intra- and inter-assays were
      repeatable. The cutoff value from TG-ROC curve analysis was 0.106. The
      specificity and sensitivity were 80 and 80%, respectively. The correlation
      coefficient (r) of absorbance values from this ELISA compared with the serum
      neutralization test was 0.76. This ELISA might be helpful for IBH diagnosis and
      surveillance.

PMID- 24141321
TI  - Differential roles of cyclooxygenase-2-related signaling in regulating
      hypothalamic neuronal activity under various acute stresses.
AB  - We have previously suggested that activation of the hypothalamic-pituitary
      adrenal (HPA) axis is dependent on cyclooxygenase (COX)-2-related signaling under
      infectious and restraint stresses, but less dependent on it under hypoglycemic
      stress. In the present study, we evaluated the neuronal activity in the brain to
      elucidate the possible mechanisms underlying a stress-specific relevance between
      COX-2-related signaling and activation of the HPA axis under infectious
      (lipopolysaccharide, LPS), hypoglycemic (2-deoxy-D-glucose, 2DG) and restraint (1
      hr) stress conditions. The number of c-Fos-immunoreactive (IR) cells in several
      brain regions including the paraventricular nucleus (PVN) and supraoptic nucleus
      (SON) was increased at 120 min after application of all stress stimuli. The
      number of c-Fos-IR cells at 30 min was increased only by 2DG in the SON, but not
      in the PVN. In the PVN, a selective COX-2 inhibitor (NS-398) did not affect the
      number of c-Fos-IR cells at any time points. On the other hand, in the SON, NS
      398 increased c-Fos-IR cells at 30 min after LPS and restraint stresses, but not
      after 2DG injection. These results suggest that, among the brain regions
      responding to acute stresses, the PVN and SON are commonly activated under three
      acute stresses. In addition, it is also suggested that COX-2-related signaling
      decreases neuronal activity in the SON under infectious and restraint, but not
      hypoglycemic, stresses, which may be involved in the suppression of the HPA axis.

PMID- 24141322
TI  - [4 + 3] and [4 + 2] mechanisms of the Diels-Alder reactions of vinylboranes: an
      analysis of the electron charge density distribution.
AB  - The Diels-Alder (DA) reactions of isoprene with vinylborane, dimethylvinylborane
      and dichlorovinylborane have been studied using density functional theory and the
      quantum theory of atoms in molecules. We evaluated the topological properties of
      the transition structures (TSs) and the evolution of such properties along the
      reaction paths. In accordance with previous studies, our results indicate that
      the endo TSs of the reaction with vinylborane present high [4 + 3] character,
      while the exo TSs and all the TSs of the reactions with dimethylvinylborane and
      dichlorovinylborane have [4 + 2] character. The higher charge concentration
      between the diene and the dienophile appears to account for the greater
      stabilization of the [4 + 3] TSs. The [4 + 3] structure turns into the [4 + 2]
      structure through a conflict mechanism in which the C1 and B atoms compete to
      become attached to C6. The C6-B interaction, present from early steps of the
      reaction until beyond the TSs, plays a key role in facilitating the formation of
      the new sigma-bonds. The [4 + 3] and [4 + 2] mechanisms for the DA reactions of
      boron-substituted dienophiles may be distinguished by analyzing the profile of
      the ellipticity at the C1-C6 bcp along the course of the reaction. 

PMID- 24141323
TI  - Neurological injury after neonatal cardiac surgery: a randomized, controlled
      trial of 2 perfusion techniques.
AB  - BACKGROUND: Complex neonatal cardiac surgery is associated with cerebral injury.
      In particular, aortic arch repair, requiring either deep hypothermic circulatory
      arrest (DHCA) or antegrade cerebral perfusion (ACP), entails a high risk of
      perioperative injury. It is unknown whether ACP results in less cerebral injury
      than DHCA. METHODS AND RESULTS: Thirty-seven neonates with an aortic arch
      obstruction presenting for univentricular or biventricular repair were randomized
      to either DHCA or ACP. Preoperatively and 1 week after surgery, magnetic
      resonance imaging was performed in 36 patients (1 patient died during the
      hospital stay). The presence of new postoperative cerebral injury was scored, and
      results were entered into a sequential analysis, which allows for immediate data
      analysis. After the 36th patient, it was clear that there was no difference
      between DHCA and ACP in terms of new cerebral injury. Preoperatively, 50% of
      patients had evidence of cerebral injury. Postoperatively, 14 of 18 DHCA patients
      (78%) had new injury versus 13 of 18 ACP patients (72%) (P=0.66). White matter
      injury was the most common type of injury in both groups, but central infarctions
      occurred exclusively after ACP (0 vs. 6/18 [33%]; P=0.02). Early motor and
      cognitive outcomes at 24 months were assessed and were similar between groups
      (P=0.28 and P=0.25, respectively). Additional analysis revealed lower
      postoperative arterial Pco2 as a risk factor for new white matter injury
      (P=0.04). CONCLUSIONS: In this group of neonates undergoing complex cardiac
      surgery, we were unable to demonstrate a difference in the incidence of
      perioperative cerebral injury after ACP compared with DHCA. Both techniques
      resulted in a high incidence of new white matter injury, with central infarctions
      occurring exclusively after ACP. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01032876.

PMID- 24141325
TI  - Text messaging as adjunct to community-based weight management program.
AB  - Increasing obesity rates are still a public health priority. The primary aim of
      this study was to evaluate the effect of tailored text messages on body weight
      change in overweight and obese adults in a community-based weight management
      program. A secondary aim was to detect behavioral changes in the same population.
      The study design was quasi-experimental with pretest and posttest analysis,
      conducted over 12 weeks. A total of 28 participants were included in the
      analysis. Body weight, eating behaviors, exercise and nutrition self-efficacy,
      attitude toward mobile technology, social support, and physical activity were
      assessed at baseline and at 12 weeks. Text messages were sent biweekly to the
      intervention but not to the control group. At 12 weeks, the intervention group
      had lost significant weight as compared with the control group. There was a trend
      toward an improvement in eating behaviors, exercise, and nutrition self-efficacy
      in the intervention group, with no significant difference between groups. A total
      of 79% of participants stated that text messages helped in adopting healthy
      behaviors. Tailored text messages appear to enhance weight loss in a weight
      management program at a community setting. Large-scale and long-term intervention
      studies are needed to confirm these findings. 

PMID- 24141324
TI  - Dyslipidemia, coronary artery calcium, and incident atherosclerotic
      cardiovascular disease: implications for statin therapy from the multi-ethnic
      study of atherosclerosis.
AB  - BACKGROUND: Worldwide clinical practice guidelines for dyslipidemia emphasize
      allocating statin therapy to those at the highest absolute atherosclerotic
      cardiovascular disease (CVD) risk. METHODS AND RESULTS: We examined 5534 Multi
      Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline
      medications for dyslipidemia. Participants were classified by baseline coronary
      artery calcium (CAC) score (>0, >= 100) and the common clinical scheme of
      counting lipid abnormalities (LA), including low-density lipoprotein cholesterol
      >= 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40
      mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides >= 1.69
      mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial
      infarction, angina resulting in revascularization, resuscitated cardiac arrest,
      stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than
      half of events (55%) occurred in the 21% of participants with CAC >= 100.
      Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with
      CAC >= 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA
      categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000
      person-years across LA categories. Individuals with 0 LA and CAC >= 100 had a
      higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9
      per 1000 person-years). Similar results were obtained when we classified LA using
      data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low
      density lipoprotein particle concentration and guideline categories of low
      density lipoprotein cholesterol or non-high-density lipoprotein cholesterol.
      CONCLUSIONS: CAC may have the potential to help match statin therapy to absolute
      CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary
      prevention populations were observed for patients with CAC >= 100.

PMID- 24141326
TI  - Interpretation of negative second virial coefficients from non-attractive protein
      solution osmotic pressure data: an alternate perspective.
AB  - A negative second virial coefficient has long been a predictor of potential
      protein crystallization and salting out. However, the assumption that this is due
      to attractive solute-solute interactions remains a source of debate. Here we
      reexamine the second virial coefficient from protein osmometry in terms of the
      free-solvent model. The free-solvent model has been shown to provide excellent
      predictions of the osmotic pressure of concentrated and crowded environments for
      aqueous protein solutions in moderate ionic strengths. The free-solvent model
      relies on two critical parameters, hydration and ion binding, both which can be
      determined independently of osmotic pressure data. Herein, the free-solvent model
      is mathematically represented as a virial expansion model and the second virial
      coefficient is expressed in terms of solute-solvent interactions, namely
      hydration and ion binding. Hydration and ion binding values are then used to
      estimate the second virial coefficient at various protein concentrations for
      three model proteins ovalbumin (OVA), bovine serum albumin (BSA), and hen egg
      lysozyme (HEL) in various monovalent salt aqueous solutions. The results show
      that the conditions for obtaining a negative second virial coefficient emerge
      when the ionic strength of the influenced region of the protein is higher than
      that of the bulk. This analysis suggests a plausible explanation as to why
      proteins are more favorable for salting out or crystallization when the solution
      is represented by a negative second virial coefficient. 

PMID- 24141327
TI  - Robust pluripotent stem cell expansion and cardiomyocyte differentiation via
      geometric patterning.
AB  - Geometric factors including the size, shape, density, and spacing of pluripotent
      stem cell colonies play a significant role in the maintenance of pluripotency and
      in cell fate determination. These factors are impossible to control using
      standard tissue culture methods. As such, there can be substantial batch-to-batch
      variability in cell line maintenance and differentiation yield. Here, we
      demonstrate a simple, robust technique for pluripotent stem cell expansion and
      cardiomyocyte differentiation by patterning cell colonies with a silicone
      stencil. We have observed that patterning human induced pluripotent stem cell
      (hiPSC) colonies improves the uniformity and repeatability of their size,
      density, and shape. Uniformity of colony geometry leads to improved homogeneity
      in the expression of pluripotency markers SSEA4 and Nanog as compared with
      conventional clump passaging. Patterned cell colonies are capable of undergoing
      directed differentiation into spontaneously beating cardiomyocyte clusters with
      improved yield and repeatability over unpatterned cultures seeded either as cell
      clumps or uniform single cell suspensions. Circular patterns result in a highly
      repeatable 3D ring-shaped band of cardiomyocytes which electrically couple and
      lead to propagating contraction waves around the ring. Because of these
      advantages, geometrically patterning stem cells using stencils may offer greater
      repeatability from batch-to-batch and person-to-person, an increase in
      differentiation yield, a faster experimental workflow, and a simpler protocol to
      communicate and follow. Furthermore, the ability to control where cardiomyocytes
      arise across a culture well during differentiation could greatly aid the design
      of electrophysiological assays for drug-screening. 

PMID- 24141328
TI  - The proton conducting electrolyte BaTi0.5In0.5O2.75: determination of the
      deuteron site and its local environment.
AB  - Deuterated BaTi0.5In0.5O2.75 has been studied with neutron total (Bragg plus
      diffuse) scattering data, using both the Rietveld refinement method and the
      reverse Monte Carlo (RMC) modelling technique, to investigate the preferred
      proton site and its local structural environment. The Rietveld analysis shows an
      excellent fit between experimental data and a long-range cubic description of the
      BaTi0.5In0.5O2.53(OD)0.44 perovskite structure containing a statistical
      distribution of Ti and In ions at the centre of regular (Ti/In)O6 octahedra.
      However, an RMC analysis of the data reveals substantial local structural
      features that reflect limitations of the Rietveld method for studies of this
      type. The Ti-O and In-O pair distribution functions given by the RMC analysis are
      markedly different from each other, with average Ti-O and In-O bond distances of
      2.035 A and 2.159 A, respectively. The InO6 octahedra are regular in shape
      whereas the TiO6 octahedra are distorted. The average O-D bond distance is
      roughly 0.96 A, and the preferred deuteron sites have a second nearest oxygen
      distance of 2.13 A, which confirms localized tilting of the deuteron and
      indicates a substantial degree of hydrogen bonding. The impact of octahedral
      distortion and hydrogen bonding on the proton conduction mechanism is discussed.

PMID- 24141329
TI  - Observation of d-p hybridized aromaticity in lanthanum-doped boron clusters.
AB  - The concept of aromaticity has been advanced beyond the framework of organic
      chemistry, and multiple aromaticity (sigma, pi, and delta) has been observed to
      account for the highly symmetric structures or unusual stability of the clusters.
      In the present study, the electronic structures and chemical bonding of small
      monolanthanum boride clusters are investigated using photoelectron imaging
      spectroscopy and first principles electronic structure calculations. Accurate
      electron affinities of 1.32 +/- 0.04 and 1.13 +/- 0.06 eV for the neutral LaB2
      and LaB3 clusters are obtained by the vibrationally-resolved photoelectron
      spectra of the LaB2(-) and LaB3(-) clusters, respectively. It is shown that LaB2(
      ) and LaB3 exhibit enhanced stability in their respective cluster series, as
      evidenced from the calculated removal energies and HOMO-LUMO gaps. Molecular
      orbital analysis discloses that these two clusters possess doubly aromatic
      characters (sigma and pi), responsible for their enhanced stability.
      Interestingly, unlike conventional sigma-, pi-, and delta-aromaticity formed by
      the delocalization of unhybridized p or d orbitals, the sigma and pi delocalized
      molecular orbitals shown here are formed through the effective overlap between
      the 5d atomic orbital of the La atom and the p orbitals of the remaining boron
      atoms, representing an intriguing d-p hybridized aromaticity. 

PMID- 24141330
TI  - Clinical significance of SF3B1 mutations in Korean patients with myelodysplastic
      syndromes and myelodysplasia/myeloproliferative neoplasms with ring sideroblasts.
AB  - Somatic mutations in the SF3B1 gene, a gene encoding the splicing factor 3B
      subunit 1, were recently reported in myelodysplastic syndromes (MDS),
      particularly in the presence of ring sideroblasts (RS). The authors investigated
      the prevalence and clinical significance of SF3B1 mutations in Korean patients
      with myeloid neoplasms with RS. The study subjects were 43 Korean patients with
      myeloid neoplasms. Twenty-nine patients (67 %) had 15 % or more RS (high-count RS
      [HC-RS]), and 14 (33 %) had RS less than 15 % (low-count RS [LC-RS]). Molecular
      genetic tests were performed to detect SF3B1 mutations by direct sequencing on
      bone marrow samples of the patients. SF3B1 mutations were detected in 55 %
      (16/29) of the HC-RS group: 3 RARS (3/3), 8 RCMD (8/16), 3 RARS-t (3/4), 1 RAEB
      (1/4), and 1 MDS-U (1/1). All mutations were previously reported mutations with
      K700E being the most common (63 % of mutation-positive cases). On the other hand,
      none (0 %) of the LC-RS group had SF3B1 mutation. The patients with SF3B1
      mutations had higher platelet counts (p = 0.023), higher proportions of RS (p =
      0.003), and lower proportions of bone marrow blasts (p = 0.026) than those
      without SF3B1 mutations. SF3B1 mutations showed a favorable survival implication
      (p = 0.025), but not in multivariate analysis (p = 0.178). This study confirmed
      that SF3B1 mutation is highly specific to the HC-RS phenotype in Korean patients
      with myeloid neoplasms with similar frequencies and distributions in previous
      findings and is associated with distinct hematologic features.

PMID- 24141331
TI  - Peripheral blood lymphocyte/monocyte ratio predicts outcome for patients with
      diffuse large B cell lymphoma after standard first-line regimens.
AB  - To determine whether peripheral blood absolute lymphocyte/absolute monocyte
      counts ratio (ALC/AMC ratio) at diagnosis predicts survival of diffuse large B
      cell lymphoma (DLBCL) patients treated with standard first-line regimens, we
      retrospectively analyzed 244 patients with DLBCL who were treated with standard
      cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, or rituximab
      cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone. Progression
      free survival and overall survival (PFS and OS) were estimated using the Kaplan
      Meier method and two-tailed log-rank; The Cox proportional hazards model was used
      to evaluate ALC/AMC ratio as prognostic factors when adjusting for the
      International Prognostic Index (IPI). On univariate and multivariate analyses
      performed with factors included in the IPI, the ALC/AMC ratio at diagnosis
      remained an independent predictor of OS and PFS (OS: P < 0.001; PFS: P < 0.001).
      Patients with lower ALC/AMC ratio (<3.8) seemed to have lower complete remission
      rate, 2-year PFS and 3-year OS when compared to patients with ALC/AMC ratio
      >=3.8, respectively (26 versus 90 %, P < 0.001; 18 versus 82 %, P < 0.001; 24
      versus 86 %; P < 0.001, respectively). Moreover, the ALC/AMC ratio was able to
      further risk-stratify IPI 0-2 and three-five risk patient groups, respectively.
      The ALC/AMC ratio at the time of diagnosis may provide additional prognostic
      information beyond that of the IPI for patients with DLBCL who receive standard
      first-line regimens.

PMID- 24141332
TI  - Iron deficiency anemia as a risk factor for cerebrovascular events in early
      childhood: a case-control study.
AB  - In recent years, iron-deficiency anemia (IDA) has been suggested to have an
      association with childhood-onset ischemic stroke in otherwise healthy children,
      but few cases have proven it thus far. In this study, we aimed to investigate
      whether iron-deficiency anemia is a risk factor for cerebrovascular events and
      childhood-onset ischemic stroke in previously healthy children. This was a case
      control study that included 21 stroke cases with patients who had previously been
      generally healthy, and matched with age and gender of 100 healthy control
      subjects. Patients were included if a diagnosis of definite stroke had been made
      and other known etiologies of childhood onset stroke were excluded. For all
      subjects, iron parameters including serum iron, ferritin, transferrin, total iron
      binding capacity, and transferrin saturation were assessed. We screened all case
      patients for prothrombotic factors including level of hemoglobin S, protein C,
      protein S, antithrombin III, lupus anticoagulant, factor V Leiden, and
      prothrombin gene mutation (G20210A). Brain magnetic resonance images (MRI),
      magnetic resonance angiography (MRA), and magnetic resonance venography (MRV)
      were performed to all case patients. All case patients have normal results
      regarding functional, immunological, and molecular assay for prothrombotic
      factors screening. Our results showed that IDA was disclosed in 57.1 % of stroke
      cases with no identified cause, as compared to 26 % of controls. Our study
      suggest that previously healthy children who developed stroke are 3.8 times more
      likely to have IDA than healthy children, who do not develop stroke (OR, 3.8; 95
      % CI:1.3-11.2 P = 0.005). In addition, there was significant interaction between
      IDA and thrombocytosis among studied cases (OR, 10.5; 95 % CI, 1.0-152 P = 0.02).
      There were nonsignificant differences between stroke patients with IDA and those
      with normal iron parameters regarding stroke subtype (P > 0.05). Public health
      messages on the importance of early detection of iron-deficiency anemia in young
      children, especially in our developing countries so that it can be treated before
      a life-threatening complication like stroke develops.

PMID- 24141334
TI  - Bone marrow aspirate smear preparation: morphological superiority of the timely
      wedge smear and the importance of imprints.

PMID- 24141333
TI  - BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression
      of human multiple myeloma.
AB  - Tumour necrosis factor alpha (TNF-alpha) is an inflammatory cytokine with a wide
      spectrum of biological activity, including angiogenesis. B cell activating factor
      (BAFF) and a proliferation-inducing ligand (APRIL) are members of the TNF-alpha
      family. Vascular endothelial growth factor (VEGF), on the other hand, is one of
      the most characteristic pro-angiogenic cytokines produced by multiple cell types
      in multiple myeloma (MM). We have analysed BAFF and APRIL concentrations in
      parallel with pro-angiogenic cytokines in serum and trephine biopsy, and the bone
      marrow microvascular density (MVD) in 50 patients with newly diagnosed IgG MM and
      24 healthy volunteers. The study showed statistically higher concentrations of
      BAFF, APRIL and TNF-alpha, as well as VEGF and its receptor, in MM patients
      compared to healthy volunteers and patients in advanced stages of the disease. A
      statistically positive correlation between the concentration of TNF-alpha and the
      expression of VEGF was demonstrated, and so was a positive link between BAFF,
      APRIL, MVD and lactate dehydrogenase (LDH). Furthermore, we observed a
      significant decrease in all studied cytokines after anti-angiogenic therapy, with
      meaningful differences between responders (at least partial remission) and
      patients with stable disease. It was also established that APRIL, but not BAFF,
      correlated with pro-angiogenic cytokines such as VEGF with its receptor, MVD and
      syndecan-1. Finally, our results showed that serum BAFF and APRIL levels could be
      useful biomarkers of MM disease activity and its progression which suggests that
      APRIL could be a possible novel therapeutic target in MM. 

PMID- 24141335
TI  - Mast cell sarcoma mimicking metastatic colon carcinoma.

PMID- 24141336
TI  - Pretransplant hyperferritinemia has no effect on the outcome of myeloablative
      cord blood transplantation for acute leukemia and myelodysplastic syndrome.

PMID- 24141339
TI  - Restoring Segmental Biomechanics Through Nucleus Augmentation: An In Vitro Study.
AB  - STUDY DESIGN: In vitro biomechanical laboratory study. OBJECTIVES: The purpose of
      this study is to evaluate a mechanical treatment to create a degenerative motion
      segment and the ability of nucleus augmentation to restore biomechanics. SUMMARY
      OF BACKGROUND: In cases with an intact annulus fibrosus, the replacement or
      augmentation of the nucleus pulposus alone may provide a less invasive option to
      restore normal biomechanics and disk height when compared with spinal fusion or
      total disk replacement. Laboratory testing allows these changes to be fully
      characterized. However, without preexisting pathology, nucleus augmentation
      therapies are difficult to evaluate in vitro. METHODS: The present study
      evaluated pure moment bending and compressive biomechanics in 3 states (n=6): (1)
      intact, (2) after creep loading and nucleus disruption to induce degenerative
      biomechanical changes, and (3) after nucleus augmentation through an injectable
      polymer (DiscCell). RESULTS: Neutral zone and ROM were increased in all modes of
      bending after the degenerative treatment. The most sensitive mode of bending was
      lateral bending, with intact ROM (20.0+/-2.9 degrees) increased to 22.3+/-2.6
      degrees after degenerative treatment and reduced to 18.4+/-1.6 degrees after
      injection of the polymer. All bending ROM and NZ changes induced by the
      degenerative treatment were reversed by nucleus augmentation. CONCLUSIONS: This
      material was shown to be effective at altering motion segment biomechanics and
      restoring disk height during time zero tests. This technique may provide a model
      to examine the time zero performance of a nucleus augmentation device/material.

PMID- 24141342
TI  - Comparison of the Wake-up Test and Combined TES-MEP and CSEP Monitoring in Spinal
      Surgery.
AB  - STUDY DESIGN: A retrospective clinical analysis. OBJECTIVE: The aim of this study
      was to compare the effectiveness of the wake-up test with that of combined
      monitoring of transcranial electrical stimulation motor evoked potentials (TES
      MEP) and cortical somatosensory evoked potentials (CSEP) in spinal surgery.
      SUMMARY OF BACKGROUND DATA: TES-MEP/CSEP combined monitoring is being
      increasingly recognized as the ideal approach to detect spinal neurophysiological
      compromise during spinal surgery; however, as a result the merit of the wake-up
      test is now in doubt. MATERIALS AND METHODS: TES-MEP/CSEP combined monitoring was
      performed simultaneously in 426 patients who underwent spinal surgery at our
      department, and wake-up tests were conducted on 23 patients because of positive
      neurophysiological monitoring results with uncertain causes or persistent
      positive monitoring findings after all potential causes had been resolved.
      Preoperative and postoperative neurological examinations were performed as the
      gold standard to detect irreversible spinal function compromise. All data were
      collected to compare the efficiency of TES-MEP/CSEP combined monitoring with that
      of the wake-up test. RESULTS: Positive results of TES-MEP/CSEP combined
      monitoring were recorded in 64 cases. Among them, the positive monitoring
      findings agreed with the results of the neurological examination in 51 cases, and
      the monitoring results did not match that of neurological examination in 13
      cases. No false-negative result was observed. The sensitivity of TES-MEP/CSEP
      monitoring was 100%, the specificity was 96.5%, and the Youden index was 0.965.
      Wake-up tests were conducted in 23 cases. In 8 patients the positive monitoring
      findings completely matched the postoperative neurological examination results.
      In contrast, in the other 15 cases with negative neurophysiological monitoring
      results, only 9 patients retained intact neurological function and 6 patients
      suffered compromised neurological function. The sensitivity of the wake-up test
      was 57.1%, the specificity was 100%, and the Youden index was 0.571. CONCLUSIONS:
      Combined TES-MEP and CSEP monitoring, with its high sensitivity and specificity,
      is an effective method for monitoring spinal function during surgery and should
      be the preferred choice. The wake-up test is a useful complementary method for
      monitoring because of its high specificity.

PMID- 24141343
TI  - [Art, experience and science. Challenges in Behcet's disease].

PMID- 24141344
TI  - Mucocutaneous manifestations of Behcet's disease.
AB  - Behcet's disease is a relapsing multisystem polysymptomatic disease with
      exacerbations and remissions defined by the presence of the major symptom,
      recurrent oral aphthous ulcers, plus two of the following: recurrent genital
      ulceration, eye lesions, skin lesions or a positive pathergy test. Mucocutaneous
      manifestations like oral and genital ulcers, and cutaneous lesions
      (papulopustular lesions, erythema nodosum-like lesions, cutaneous ulcers,
      superficial thrombophlebitis), are considered the ?"fingerprint?" of the disease,
      being the most common and often the first signs to appear. Although the exact
      etiopathogenesis is still not known, genetic predispose and environmental factors
      may influence and contribute to the development of this disease. Diagnosis is
      based in the International Study Group criteria. During the last years, this
      disease has been largely studied and new immunological data and treatment
      strategies have been postulated. Despite that, further studies and attention to
      new data are needed. 

PMID- 24141345
TI  - Malignancy associated with dermatomyositis - a retrospective single-center study
      with 33 patients.
AB  - BACKGROUND: Dermatomyositis is a multisystemic inflammatory disease that has been
      associated with neoplastic disease. OBJECTIVES: To assess the clinical/
      laboratory data in a series of patients with dermatomyositis (DM) and identify
      associations with malignancy. MATERIAL AND METHODS: Retrospective study of DM
      inpatient files between 1965 and 2011. The patients were included if fulfilled at
      least four of the five Bohan and Peter diagnostic criteria. DM was considered
      associated with malignancy only if its diagnosis had preceded or followed the DM
      diagnosis by up to three years. Data was analyzed with a significance level of
      5%. RESULTS: Our results have a retrospective nature and represent only a single
      center experience. Between 1965 and 2011, 33 patients fulfilled the inclusion
      criteria, with a median age of 56 years old (s= 14.329) and female to male ratio
      of 1.36:1. Neoplastic disease was associated to DM in 30% of the patients and men
      had significantly more cases of associated neoplasia than women (p=0.042 in
      Fisher's exact test). In 70% of these patients, malignancy was diagnosed
      simultaneously or in the first year after DM diagnosis. CONCLUSIONS: In our
      series, DM was more frequent in women but, when associated with malignancy, it
      was more frequent in men, in contrast to the female predominance reported in
      Western series. Malignancy was found in about one third of DM patients and, in
      terms of target organs, did not differ from the general population. Therefore, as
      the majority of malignancies were detected at the time of or in the year
      following DM diagnosis, screening should be performed for the most frequent
      neoplasms at the time of diagnosis and repeated one year later.

PMID- 24141346
TI  - Neurogenic thoracic outlet syndrome associated with cervical rib.
AB  - A true neurogenic thoracic outlet syndrome (TOS) associated with a cervical rib
      is considered extremely rare. The authors present their experience with 5 cases
      of true neurogenic TOS associated with a cervical rib. All patients were female
      and had a cervical rib confirmed radiographically pre-operatively. Average age
      was 34,8 years. Although all patients had been treated with several combinations
      of diverse drugs and a rehabilitation program before referral to surgery, all
      described their pain as intense and debilitating before surgical treatment. All
      patients had pre-operative electromyographic abnormalities. Patients were
      operated on via a supraclavicular approach and the cervical rib was resected. No
      intra-operative or postoperative complications were noted. Two years
      postoperatively, all patients mentioned improvement. However, only 2 were
      symptomless, and on no medication. In one patient there was significant
      improvement, and in the remaining 2 patients some residual pain persisted that
      had to be dealt with pharmacologically. All patients were able to resume their
      daily life activities. Recovery was poorer in the 2 patients that had been
      referred to surgery after a longer period of time since the beginning of
      symptoms. 

PMID- 24141347
TI  - A FRAX model for the estimation of osteoporotic fracture probability in Portugal.
AB  - INTRODUCTION: The objective of this study was to develop a Portuguese version of
      the World Health Organization fracture risk assessment tool (FRAX(r)). METHODS:
      All cases of hip fracture occurred at or after 40 years of age were extracted
      from the Portuguese National Hospital Discharge Register from 2006 to 2010. Age
      and sex-ranked population estimates and mortality rates were obtained from
      National Statistics. Age- and gender stratified incidences were computed and the
      average of the five years under consideration was taken. Rates for other major
      fractures were imputed from the epidemiology of Sweden, as undertaken for most
      national FRAX(r) models. All methodological aspects and results were submitted to
      critical appraisal by a wide panel of national experts and representatives of the
      different stakeholders, including patients. RESULTS: Hip fracture incidence rates
      were higher in women than in men and increased with age. The lowest incidence was
      observed in 40-44 years group (14.1 and 4.0 per 100,000 inhabitants for men and
      women, respectively). The highest rate was observed among the 95-100 age-group
      (2,577.6 and 3,551.8/100,000 inhabitants, for men and women, respectively). The
      estimated ten-year probability for major osteoporotic fracture or hip fracture
      increased with decreasing T-score and with increasing age. CONCLUSIONS: Portugal
      has one of the lowest fracture incidences among European countries. The FRAX(r)
      tool has been successfully calibrated to the Portuguese population, and can now
      be used to estimate the ten-year risk of osteoporotic fractures in this country.
      All major stakeholders officially endorsed the Portuguese FRAX(r) model and co
      authored this paper.

PMID- 24141348
TI  - Prospective nailfold capillaroscopy evaluation of Raynaud's phenomenon in
      children and adolescents.
AB  - OBJECTIVE: To evaluate prospectively the clinical features and nailfold
      capillaroscopy findings of a cohort of children and adolescents who presented
      Raynaud's phenomenon (RP) without criteria for autoimmune rheumatic diseases.
      METHODS: 40 children and adolescents with isolated RP were included. Evidence of
      systemic autoimmune rheumatic diseases (SARD) was ruled out by thorough clinical
      and laboratory examination. Concomitantly we also performed wide-field nailfold
      capillaroscopy evaluation using an optical microscope with magnifications of 10
      and 16X. All patients were prospectively re-evaluated within a mean interval time
      between evaluations of 1.6 years. RESULTS: Thirty (75%) out of 40 patients were
      female with a mean age of 14.6 years and mean follow-up time of 4.2 years. The
      mean age of disease onset was 10.4 years and the mean time until diagnosis was
      1.4 years. Fourteen out of 40 patients (35%) presented antinuclear antibodies
      (ANA). Five (12.5%) patients had altered nailfold capillaroscopy at first
      examination: four presented non-specific microangiopathy and one presented
      scleroderma pattern. At the re-evaluation three patients (7.5%) presented
      nailfold capillaroscopy alterations (two SD pattern and one non-specific
      microangiopathy). The two patients who showed scleroderma pattern at the nailfold
      capillaroscopy presented along the follow-up a diagnosis of mixed connective
      tissue disease and hypothyroidism, respectively. One 10 year-old girl with normal
      nailfold capillaroscopy and presence of autoantibodies (ANA 1/640, nuclear
      homogeneous pattern, anti-native DNA 1/80) was diagnosed with systemic lupus
      erythematosus after 1 year of initial evaluation. None of the other children
      presented diagnosis of SARD along the follow-up. CONCLUSIONS: Primary Raynaud's
      phenomenon remained the diagnosis in most cases in this series of children and
      adolescents presenting with initial RP complaint. Nailfold capillaroscopy and
      determination of autoantibodies were useful ancillary tools in the investigation
      of possible evolution towards SARD.

PMID- 24141349
TI  - [Camurati-Engelmann disease: a case report].
AB  - Camurati-Engelmann disease (CED) or progressive diaphyseal dysplasia is a rare
      autosomal dominant hereditary disorder, characterized by symmetrical progressive
      sclerosis of long bones cortical diaphysis. Its presentation and progression is
      extremely variable. A patient of 42 years is followed in Physical Medicine and
      Rehabilitation (PMR) consultation for 7 years. He presented with pain in anterior
      thighs and legs, decreased muscle strength and functional disability. The disease
      was diagnosed 10 years ago based on radiological and histological examination of
      bone and genetic study. This patient had hypoacusis, exophthalmos and facial
      asymmetry, broad-based and waddling gait, and quadriceps atrophy. He has been
      treated with corticosteroids, non steroidal anti-inflammatory drugs (NSAIDs) and
      proton pump inhibitors (PPIs), and performs rehabilitation program for periods
      with pain symptomatic relief and mantenance of function. 

PMID- 24141350
TI  - Fibroblastic rheumatism - case report.
AB  - Fibroblastic rheumatism is a rare fibro-proliferative disease, of unknown
      etiology. It is characterized by sudden onset of symmetric inflammatory
      polyarthritis simultaneously or preceded by multiple cutaneous nodules, ranging
      from 5 to 20mm in diameter, with predilection for the upper and lower
      extremities. With only a few dozens of cases described, it has a worldwide
      distribution, affecting primarily caucasians of all ages (cases described ranging
      8 to 68 years), without gender predilection. The authors describe the case of a
      patient presenting multiple cutaneous nodules located on the back of the hands,
      without any articular or sistemyc complaints. Correlation between clinical and
      histopathological aspects led to the diagnosis and treatment, with a favorable
      outcome. 

PMID- 24141351
TI  - Arthritis, clubbing and periosteal reaction in liver failure.

PMID- 24141352
TI  - Acute low back pain - a clinical and imaging challenge.

PMID- 24141353
TI  - Anti RNP in systemic lupus erythematosus.

PMID- 24141354
TI  - Sudden hearing loss in a patient with rheumatoid arthritis; a case report and
      review of the literature.

PMID- 24141355
TI  - A study of unnatural female death profile in Lucknow, India.
AB  - Epidemiological and medicolegal, including forensic pathological, aspects of 456
      cases of unnatural deaths of females aged 16 to 30 years were studied in Lucknow
      during the period of 1 year (May 2, 2011 to May 1, 2012). These constituted 62.5%
      of the total unnatural deaths autopsied from all ages in females. Most of the
      victims were young Hindu housewives killed or who died within 7 years of
      marriage. The most common cause was vehicular accidents followed by poisons and
      burns. The homicidal, suicidal, and accidental deaths were 87, 129, and 240,
      respectively. The common motives and circumstances were mental stress due to
      various reasons, family quarrel, maladjustment in married life, and cruelty by
      the in-laws. Level of education, joint family structure, unemployment, dependence
      of the woman on the in-laws, infidelity, large families, and failure in love in
      unmarried girls were other contributing factors affecting the incidence. The
      study suggests different measures to check unnatural female deaths to improve the
      situation. 

PMID- 24141356
TI  - Nitrogen-plastic bag suicide: a case report.
AB  - The use of pure nitrogen gas to commit suicide has recently become more popular,
      although suicides involving nitrogen oxide fumes have been occasionally reported
      in the past. The cause of death in such cases is attributed to asphyxia due to
      forced depletion of oxygen, a subcategory of a phenomenon dubbed environmental
      hypoxia. A case of a 26-year-old man who committed suicide by inhaling nitrogen
      through a plastic bag is reported. The exact method of suicide used here is one
      of the many described in detail on the Web. 

PMID- 24141357
TI  - The effect of intermediate clothing targets on shotgun ballistics.
AB  - The ballistic properties of shotgun shells are complex because of multiple
      projectiles fired simultaneously that interact and spread out to affect their
      energy relayed to a human target. Intermediate targets such as clothing can
      affect penetration into tissues. We studied the effect of common clothing fabrics
      as intermediate targets on penetration of shotgun shell pellets, using ordnance
      gelatin to simulate soft tissue and thin cowhide to simulate skin. A standard 12
      gauge shotgun with modified choke was used with no. 8 shot ammunition. We found
      that protection afforded by fabrics to reduce penetration of shotgun pellets into
      tissues was greater at increasing distance from the muzzle beyond 40 yd (36.6 m).
      The thicker denim and cotton fabrics provided slightly greater protection than
      polyester. This study demonstrates that clothing modifies the potential wound
      patterns to victims of shotgun injuries. 

PMID- 24141358
TI  - Whole genome comparison of donor and cloned dogs.
AB  - Cloning is a process that produces genetically identical organisms. However, the
      genomic degree of genetic resemblance in clones needs to be determined. In this
      report, the genomes of a cloned dog and its donor were compared. Compared with a
      human monozygotic twin, the genome of the cloned dog showed little difference
      from the genome of the nuclear donor dog in terms of single nucleotide
      variations, chromosomal instability, and telomere lengths. These findings suggest
      that cloning by somatic cell nuclear transfer produced an almost identical
      genome. The whole genome sequence data of donor and cloned dogs can provide a
      resource for further investigations on epigenetic contributions in phenotypic
      differences. 

PMID- 24141359
TI  - Carbon nanofluidics of rapid water transport for energy applications.
AB  - Fast transport of water inside nanoscale graphitic surfaces, namely carbon
      nanotubes and graphene, forms the basis of aqueous carbon nanofluidic phenomena
      for which there are numerous applications in energy and environmental fields. In
      this tutorial review, we provide the basic principles of nanofluidics using
      carbon materials. We also address thermodynamic and structural aspects of
      favourable water confinement between hydrophobic carbon surfaces. We outline the
      experimental and theoretical history and consider the current status of ultrafast
      water transport inside carbon nanotubes, together with recent applications of
      aqueous carbon nanofluidic phenomena for energy generation and energy storage. We
      briefly discuss the challenges and opportunities for utilization of fast water
      transport in the graphitic nanoenvironment as a means to offer a clean and
      sustainable source of energy technology. 

PMID- 24141360
TI  - Student pharmacists' attitudes toward complementary and alternative medicine.
AB  - OBJECTIVES: To explore student pharmacists' attitudes toward complementary and
      alternative medicine (CAM) and examine factors shaping students' attitudes.
      DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: Electronic
      survey of student pharmacists between March and October 2011. PARTICIPANTS: 887
      student pharmacists in 10 U.S. colleges/schools of pharmacy. INTERVENTION: Cross
      sectional survey. MAIN OUTCOME MEASURES: Student pharmacists' attitudes regarding
      CAM using the attitudes toward CAM scale (15 items), attitudes toward specific
      CAM therapies (13 items), influence of factors (e.g., coursework, personal
      experience) on attitudes (18 items), and demographic characteristics (15 items).
      RESULTS: Mean (+/-SD) score on the attitudes toward CAM scale was 52.57 +/- 7.65
      (of a possible 75; higher score indicated more favorable attitudes). Students
      agreed that a patient's health beliefs should be integrated in the patient care
      process (4.39 +/- 0.70 [of 5]) and that knowledge about CAM would be required in
      future pharmacy practice (4.05 +/- 0.83). Scores on the attitudes toward CAM
      scale varied by gender (women higher than men, P = 0.001), race/ethnicity
      (nonwhite higher than white, P < 0.001), type of institution (private higher than
      public, P < 0.001), previous CAM coursework (P < 0.001), and previous CAM use (P
      < 0.001). Personal experience, pharmacy education (e.g., coursework and faculty
      attitudes), and family background were important factors shaping students'
      attitudes. CONCLUSION: Student pharmacists hold generally favorable views of CAM,
      and both personal and educational factors shape their views. These results
      provide insight into factors shaping future pharmacists' perceptions of CAM.
      Additional research is needed to examine how attitudes influence future
      pharmacists' confidence and willingness to talk to patients about CAM.

PMID- 24141361
TI  - Controlling the electronic properties of SWCNT FETs via modification of the
      substrate surface prior to atomic layer deposition of 10 nm thick Al2O3 film.
AB  - We demonstrate the controllability of the electronic transport properties of
      single-walled carbon nanotube (SWCNT) field effect transistors (FETs) via the use
      of 10 nm thick atomic-layer-deposited aluminum oxide (Al2O3) gate dielectric
      films, where the substrate surfaces were modified with differently functionalized
      self-assembled monolayers (SAMs) prior to their growth, namely SAMs with
      hydrophobic (-CH3) or hydrophilic (-OH) groups. Al2O3 grown on a hydrophilic
      surface causes the SWCNT FETs to keep their intrinsic p-type transfer
      characteristics by alleviating the electron-doping effect originating from
      defects in the Al2O3 film. However, the SAM with methyl groups increases the
      defect density of the Al2O3 film, enhancing the n-type transfer characteristics
      and inducing ambipolar to n-type behavior in the SWCNT FETs. In this work, we
      find clues about the distribution of charged defects in the Al2O3 film, which
      strongly influences the transfer characteristics of the SWCNT FETs, by measuring
      the thickness-dependent flat band voltages. 

PMID- 24141362
TI  - Evaluating empirical bounds on complex disease genetic architecture.
AB  - The genetic architecture of human diseases governs the success of genetic mapping
      and the future of personalized medicine. Although numerous studies have queried
      the genetic basis of common disease, contradictory hypotheses have been advocated
      about features of genetic architecture (for example, the contribution of rare
      versus common variants). We developed an integrated simulation framework,
      calibrated to empirical data, to enable the systematic evaluation of such
      hypotheses. For type 2 diabetes (T2D), two simple parameters--(i) the target size
      for causal mutation and (ii) the coupling between selection and phenotypic effect
      -define a broad space of architectures. Whereas extreme models are excluded by
      the combination of epidemiology, linkage and genome-wide association studies,
      many models remain consistent, including those where rare variants explain either
      little (<25%) or most (>80%) of T2D heritability. Ongoing sequencing and
      genotyping studies will further constrain the space of possible architectures,
      but very large samples (for example, >250,000 unselected individuals) will be
      required to localize most of the heritability underlying T2D and other traits
      characterized by these models.

PMID- 24141363
TI  - A genomic variation map provides insights into the genetic basis of cucumber
      domestication and diversity.
AB  - Most fruits in our daily diet are the products of domestication and breeding.
      Here we report a map of genome variation for a major fruit that encompasses ~3.6
      million variants, generated by deep resequencing of 115 cucumber lines sampled
      from 3,342 accessions worldwide. Comparative analysis suggests that fruit crops
      underwent narrower bottlenecks during domestication than grain crops. We
      identified 112 putative domestication sweeps; 1 of these regions contains a gene
      involved in the loss of bitterness in fruits, an essential domestication trait of
      cucumber. We also investigated the genomic basis of divergence among the
      cultivated populations and discovered a natural genetic variant in a beta
      carotene hydroxylase gene that could be used to breed cucumbers with enhanced
      nutritional value. The genomic history of cucumber evolution uncovered here
      provides the basis for future genomics-enabled breeding.

PMID- 24141365
TI  - Procyanidin C1 from Cinnamomi Cortex inhibits TGF-beta-induced epithelial-to
      mesenchymal transition in the A549 lung cancer cell line.
AB  - Cancer metastasis is one of the most critical events in cancer patients, and the
      median overall survival of stage IIIb or IV patients with metastatic lung cancer
      in the TNM classification is only 8 or 5 months, respectively. We previously
      demonstrated that Juzentaihoto, a Japanese traditional medicine, can inhibit
      cancer metastasis through the activation of macrophages and T cells in mouse
      cancer metastatic models; however, the mechanism(s) through which Juzentaihoto
      directly affects tumor cells during the metastasis process and which herbal
      components from Juzentaihoto inhibit the metastatic potential have not been
      elucidated. In this study, we focused on the epithelial-to-mesenchymal transition
      (EMT), which plays an important role in the formation of cancer metastasis. We
      newly determined that only the Cinnamomi Cortex (CC) extract, one of 10 herbal
      components of Juzentaihoto, inhibits TGF-beta-induced EMT. Moreover, the contents
      of catechin trimer in CC extracts were significantly correlated with the efficacy
      of inhibiting TGF-beta-induced EMT. Finally, the structure of the catechin trimer
      from CC extract was chemically identified as procyanidin C1 and the compound
      showed inhibitory activity against TGF-beta-induced EMT. This illustrates that
      procyanidin C1 is the main active compound in the CC extract responsible for EMT
      inhibition and that procyanidin C1 could be useful as a lead compound to develop
      inhibitors of cancer metastasis and other diseases related to EMT.

PMID- 24141364
TI  - Inherited GATA3 variants are associated with Ph-like childhood acute
      lymphoblastic leukemia and risk of relapse.
AB  - Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL)
      identified a high-risk subtype with an expression signature resembling that of
      Philadelphia chromosome-positive ALL and poor prognosis (Ph-like ALL). However,
      the role of inherited genetic variation in Ph-like ALL pathogenesis remains
      unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non
      ALL controls, we identified a susceptibility locus for Ph-like ALL (GATA3,
      rs3824662; P = 2.17 * 10(-14), odds ratio (OR) = 3.85 for Ph-like ALL versus non
      ALL; P = 1.05 * 10(-8), OR = 3.25 for Ph-like ALL versus non-Ph-like ALL), with
      independent validation. The rs3824662 risk allele was associated with somatic
      lesions underlying Ph-like ALL (CRLF2 rearrangement, JAK gene mutation and IKZF1
      deletion) and with variation in GATA3 expression. Finally, genotype at the GATA3
      SNP was also associated with early treatment response and risk of ALL relapse.
      Our results provide insights into interactions between inherited and somatic
      variants and their role in ALL pathogenesis and prognosis. 

PMID- 24141366
TI  - Laparoscopic Heller-Dor for primary esophageal achalasia: outcomes in 173
      patients.
AB  - AIM: Laparoscopic Heller myotomy combined with anterior (Dor) fundoplication is
      the most widely-used surgical procedure for treating esophageal achalasia in
      Europe MATERIAL OF STUDY: From November 1992 through May 2010 we performed
      laparoscopic Heller-Dor on 173 patients RESULTS: Conversion to laparotomy was
      required in three cases (1.7%) at the beginning of the experience (for mucosal)
      perforation which was the most frequent intraoperative complication, managed
      laparoscopically with the increasing experience. Five (2.9%) cases had minor
      postoperative complications. Clinical results were satisfactory in 99.4% of
      cases. One patient (0.6%) had severe persistent dysphagia. Mean esophageal
      diameter decreased from 50 mm +/- 12 (range 20- 90) to 25 mm +/- 7 (range 15-80).
      Lower esophageal sphincter pressure decreased from 32 mmHg (median, range 10- 93)
      pre-operatively to 11 mmHg (median, range 5-21) at one year follow up and
      residual pressure from 12 mmHg (median, range 3-30) to 4 mmHg (median, range 1
      8). Impedance and pH monitoring showed normal levels in 39/47 (83%) patients who
      agreed to testing. CONCLUSION: The good outcomes of this experience, in part due
      to careful adherence to technical aspects of the operation, confirm that the
      laparoscopic Heller-Dor is the gold standard surgical treatment for esophageal
      achalasia.

PMID- 24141367
TI  - Protective effect of demethylation treatment on cigarette smoke extract-induced
      mouse emphysema model.
AB  - In the present study, we explored the effects of demethylation in a cigarette
      smoke extract (CSE)-induced mouse emphysema model. Animals were randomly assigned
      to the control group, CSE group, 5-aza-2'-deoxycytidine (AZA) group, and CSE+AZA
      group (n = 10 per group). The mitochondrial transcription factor A (mtTFA)
      promoter methylation increased over 4-fold in the CSE group compared with the
      control group, which was reversed by AZA. The mtTFA and the cytochrome c oxidase
      subunit II (COX II) mRNA and protein levels were decreased approximately 3-fold
      in the CSE group compared with the control group, which was largely restored by
      AZA. Histological analysis showed that the CSE group exhibited emphysema compared
      with the control, which was alleviated by AZA. In addition, CSE significantly
      induced lung cell apoptosis and decreased lung function and lung mitochondrial
      COX activity, which was mostly restored by AZA. In conclusion, we for the first
      time provide evidence that demethylation therapy with AZA can effectively improve
      emphysema, lung function, lung cell apoptosis, and lung mitochondrial COX
      activity in a CSE-induced mouse emphysema model, which adds fresh insight into
      the therapeutic potential of demethylating agents in the prevention and treatment
      of cigarette smoke-induced emphysema. 

PMID- 24141368
TI  - Retraction: Nuclear receptors as targets for drug development: crosstalk between
      peroxisome proliferator-activated receptor gamma and cytokines in bone marrow
      derived mesenchymal stem cells.

PMID- 24141369
TI  - Impact of allele-level HLA matching on outcomes after myeloablative single unit
      umbilical cord blood transplantation for hematologic malignancy.
AB  - We studied the effect of allele-level matching at human leukocyte antigen (HLA)
      A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations
      for hematologic malignancy. The primary end point was nonrelapse mortality (NRM).
      Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were
      mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset,
      allele-level HLA match was assigned using imputation; concordance between HLA
      match assignment and outcome correlation was confirmed between the actual and
      imputed HLA-match groups. Compared with HLA-matched units, neutrophil recovery
      was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles. NRM was higher
      with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLA-matched
      units. The observed effects are independent of cell dose and patient age. These
      data support allele-level HLA matching in the selection of single UCB units. 

PMID- 24141371
TI  - New cross-bridged cyclam derivative CB-TE1K1P, an improved bifunctional chelator
      for copper radionuclides.
AB  - A new cross-bridged cyclam chelator, CB-TE1K1P, was developed for copper-based
      radiopharmaceuticals, and this chelator can be labelled with (64)Cu under mild
      conditions in high specific activity. DBCO-PEG4-CB-TE1K1P was synthesized for
      conjugation to proteins, while Dde-CB-TE1K1P((t)Bu2)-OH was synthesized for solid
      phase peptide synthesis. Examples of the conjugation chemistry, radiolabelling
      and serum stability of each are presented. 

PMID- 24141370
TI  - The histone methyltransferase Ezh2 is a crucial epigenetic regulator of
      allogeneic T-cell responses mediating graft-versus-host disease.
AB  - Posttranscriptional modification of histones by methylation plays an important
      role in regulating Ag-driven T-cell responses. We have recently drawn
      correlations between allogeneic T-cell responses and the histone
      methyltransferase Ezh2, which catalyzes histone H3 lysine 27 trimethylation. The
      functional relevance of Ezh2 in T-cell alloimmunity remains unclear. Here, we
      identify a central role of Ezh2 in regulating allogeneic T-cell proliferation,
      differentiation, and function. Conditional loss of Ezh2 in donor T cells
      inhibited graft-versus-host disease (GVHD) in mice after allogeneic bone marrow
      (BM) transplantation. Although Ezh2-deficient T cells were initially activated to
      proliferate upon alloantigenic priming, their ability to undergo continual
      proliferation and expansion was defective during late stages of GVHD induction.
      This effect of Ezh2 ablation was largely independent of the proapoptotic molecule
      Bim. Unexpectedly, as a gene silencer, Ezh2 was required to promote the
      expression of transcription factors Tbx21 and Stat4. Loss of Ezh2 in T cells
      specifically impaired their differentiation into interferon (IFN)-gamma-producing
      effector cells. However, Ezh2 ablation retained antileukemia activity in
      alloreactive T cells, leading to improved overall survival of the recipients. Our
      findings justify investigation of modulating Ezh2 as a therapeutic strategy for
      the treatment of GVHD and other T cell-mediated inflammatory disorders. 

PMID- 24141372
TI  - A phase II study of pemetrexed in patients with previously heavily treated non
      squamous non-small cell lung cancer (HANSHIN Oncology Group 001).
AB  - PURPOSE: Pemetrexed has shown substantial activity in non-squamous non-small cell
      lung cancer (NSCLC) and is one of the current standard agents in second-line
      settings due to its efficacy and favorable tolerability profile. We conducted
      phase II study to evaluate the safety and efficacy of pemetrexed in Japanese
      patients with previously heavily treated, advanced non-squamous NSCLC. METHODS:
      Patients with stage IIIB or IV non-squamous NSCLC, performance status (PS) 0-2,
      previous two to five regimens of chemotherapy were enrolled and received
      pemetrexed (500 mg/m(2)) on day 1 every 21 days until disease progression. The
      primary endpoint was progression-free survival (PFS). The secondary endpoints
      included overall survival (OS), objective response rate (ORR), disease control
      rate (DCR), and safety. RESULTS: From August 2009 to May 2010, 46 patients were
      enrolled: median age 65 years; 52 % women; PS 0/1/2 26/67/7 %; previous treatment
      regimen 2/3/4/5 48/28/20/4 %; epidermal growth factor receptor activating
      mutation positive/wild/unknown 30/48/22 %. The median follow-up period was 13.5
      months. The median number of treatment cycles was 4 (range 1-18 cycles). The
      median PFS was 5.2 months (95 % CI 3.0-5.8 months). The median OS was 14.4 months
      (95 % CI 9.4-21.3 months). The ORR was 8.7 % and DCR was 63.0 %. The grade 3/4
      hematological adverse events include 8 patients with leukopenia, 11 with
      neutropenia, 5 with anemia, and 2 with thrombocytopenia. There were no reports of
      febrile neutropenia and no treatment-related death was observed. CONCLUSION:
      Treatment with pemetrexed in previously heavily treated Japanese non-squamous
      NSCLC patients is feasible and shows encouraging activity.

PMID- 24141373
TI  - Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human
      meningioma.
AB  - BACKGROUND: Meningiomas are the most common type of intracranial tumor,
      accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no
      biomarkers exist to reliably predict the clinical outcome of meningiomas. A
      previous genome-wide methylation analysis revealed that HOXA9 is one of the most
      functionally relevant biomarkers. In this study, we have examined whether HOXA9
      is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor
      of the interaction between HOXA9 and its cofactor PBX. METHODS: We determined the
      expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal
      brain tissue. Meningioma in culture and in subcutaneous tumors was treated with
      HXR9. We also examined the disruption of HOXA9/PBX dimers. RESULTS: We first
      confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain
      tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an
      alteration of DNA binding, and subsequent regulation of their target genes. HXR9
      markedly inhibited the growth of meningioma cells and subcutaneous meningeal
      tumors. CONCLUSION: There is no effective chemotherapy for meningiomas at
      present, and targeting the HOXA9/PBX interaction may represent a novel treatment
      option for this disease.

PMID- 24141374
TI  - Pegylated liposomal doxorubicin and cyclophosphamide in early recurrent ovarian
      carcinoma: phase I dose-finding study.
AB  - PURPOSE: This single-arm phase I dose-escalation study determines the optimal
      dose of the non-platinum treatment pegylated liposomal doxorubicin (PLD) plus
      cyclophosphamide (CPM) every 4 weeks in early recurrent ovarian carcinoma.
      METHODS: Twenty-one women with ovarian carcinoma relapsing within 12 months of
      first-line surgery and platinum-taxane chemotherapy received escalating doses of
      PLD (35-45 mg/m(2)) and CPM (500-600 mg/m(2)) every 4 weeks for at least two
      cycles. Primary objective was assessment of maximum-tolerated dose (MTD) over the
      first two cycles. Secondary objectives were to assess safety over 2 cycles,
      efficacy evaluated every two cycles (response evaluation criteria in solid
      tumours criteria) and overall survival (OS). RESULTS: The PLD-CPM MTD was 40/600
      mg/m(2) with 2/3 patients treated at 45/500 mg/m(2), showing DLTs with Grade 3/4
      oesophagitis, thrombopenia/neutropenia, leucopoenia, and Grade 3
      stomatitis/asthenia during the first cycle of treatment. Four severe toxicities
      were reported by three patients during the two first cycles, namely Grade 4
      anaemia, and Grade 3 stomatitis. The most common treatment-related toxicities
      were anaemia (71.4 %), nausea (61.9 %), neutropenia (57.1 %), asthenia (52.4 %),
      leucopoenia (47.6 %), stomatitis (42.9 %), skin (28.6 %) and palmar-plantar
      erythrodysesthesia (19 %). No treatment-related deaths were reported. The overall
      response rate (complete and partial) was 31 %, and median OS was 8.2 months [95 %
      CI (3.3-13.2)]. CONCLUSIONS: The combination of PLD and CPM is feasible and may
      be considered particularly in cases where platinum-based treatment is not
      suitable. The recommended doses for a phase II trial are PLD 40 mg/m(2) plus CPM
      600 mg/m(2) every 4 weeks.

PMID- 24141375
TI  - A phase 1 trial of intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide
      (GSAO) in patients with advanced solid tumours.
AB  - BACKGROUND: 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water
      soluble mitochondrial toxin that binds to adenine nucleotide translocase in the
      inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1
      study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated
      dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a
      week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating
      markers of angiogenesis. METHODS: Patients with advanced solid tumours received
      GSAO in a dose-escalation trial according to a standard '3 + 3' design that was
      guided by toxicity and, for the final dose escalation, by arsenic PK data.
      RESULTS: A total of 34 patients were treated with GSAO across 9 dose levels (1.3
      44.0 mg/m(2)). Treatment was well tolerated with few adverse events. An
      additional three patients were enrolled at the 12.4 mg/m(2) dose level following
      a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m(2) dose
      level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal
      atrial fibrillation). CONCLUSIONS: The MTD of GSAO was 22.0 mg/m(2)/day. There
      was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of
      an anti-vascular effect of GSAO.

PMID- 24141376
TI  - Development and testing of the patient-reported chemotherapy indicators of
      symptoms and experience: patient-reported outcome and process indicators
      sensitive to the quality of nursing care in ambulatory chemotherapy settings.
AB  - BACKGROUND: Outcome indicators are increasingly advocated to demonstrate the
      impact of high-quality care; however, generic measures do not encompass outcomes
      relevant to specialist areas. OBJECTIVE: The aim of this study was to develop an
      outcome measure (Patient-Reported Chemotherapy Indicators of Symptoms and
      Experience [PR-CISE]) for use in ambulatory chemotherapy settings and assess its
      feasibility, acceptability, and preliminary efficacy in clinical practice.
      METHODS: Three areas were covered by PR-CISE--symptom management, safe medication
      administration, and experience of supportive care. Outcome selection was guided
      by review of evidence and reference groups of users, clinicians, and experts.
      Over 12 weeks, PR-CISE was distributed to patients receiving ambulatory
      chemotherapy at 10 cancer centers. Data were analyzed descriptively and with case
      mix adjustment using regression-based models. RESULTS: There were 2466 responses.
      There was variability across centers in terms of symptom experience and support
      provided. Across the whole sample, 25% reported moderate or severe nausea;
      however, rates varied between centers (25%-75%). Similar results emerged for
      other symptoms. When asked about support for symptom management, 80% reported
      that chemotherapy nurses asked about and were aware of symptom severity and
      provided useful information/advice. Once again, there was substantial variability
      between centers. Unexplained variation remained after case mix adjustment,
      suggesting that differences may be "real" rather than caused by population
      differences. Stakeholders planned to make changes to care delivery based on data
      on their performance. CONCLUSIONS: We successfully developed and tested
      indicators assessing the quality of care provided in ambulatory chemotherapy
      services. IMPLICATIONS: Results show that monitoring outcomes demonstrate
      potential differences in care quality and provide a stimulus to improve the
      experience and health of patients.

PMID- 24141377
TI  - Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests
      a survival benefit.
AB  - BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in
      adults. Despite successful control of the primary tumor, metastatic disease will
      ultimately develop in approximately 35% of the patients, with the liver being the
      most common site for metastases. These metastases are generally refractory to
      systemic chemotherapy, and the median survival for patients with liver metastases
      is about 6 months. This phase II trial reports the experience of isolated hepatic
      perfusion (IHP) as a treatment option. METHOD: A total of 34 patients with
      isolated liver metastasis from ocular melanoma underwent IHP. An overall survival
      comparison was made using data retrieved from the National Patient Register
      managed by the Swedish National Board of Health and Welfare. RESULTS: An overall
      radiological response was seen in 68% of the patients, with 12% having a complete
      response. Time to local progression was 7 months; 68% of the patients developed
      extrahepatic metastases after a median of 13 months, and the median overall
      survival was 24 months. There was a significant survival advantage of 14 months
      (p = 0.029) when comparing these patients with a control group consisting of the
      longest surviving patients in Sweden with uveal melanoma liver metastases not
      treated with IHP. CONCLUSIONS: IHP is a treatment option with a high response
      rate and a potential survival benefit of more than 1 year. IHP should be
      considered an option in the treatment of uveal melanoma metastases. A randomized
      trial comparing IHP and best alternative care will start during 2013 (the
      SCANDIUM trial, ClinicalTrials.gov identifier NCT01785316).

PMID- 24141379
TI  - Remarkable charge transfer between CdSe seeded CdS nanorods and its metallic and
      semiconducting tips and its effect on Rhodamine B photodegradation.
AB  - Hybrid colloids (HCs) have shown distinct optical, electric, and optoelectronic
      properties from the components, mainly because of electronic interplay between
      the components. Here we investigate different charge transfer behaviors of
      dumbbell-structured CdSe-seeded CdS nanorods with metallic and semiconducting tip
      materials respectively studied by UV-vis and photoluminescence (PL) spectra, i.e.
      gold-tipped CdSe-seeded CdS nanorods and palladium sulfide-tipped CdSe-seeded CdS
      nanorods. They have shown remarkably different optical properties due to
      different charge transfer processes, i.e. one is only excited electrons
      transferred from the CdS shell to gold tips while the other is holes as well as
      electrons injected from the CdS shell into the palladium sulfide tips. The effect
      of the charge transfer on Rhodamine B (RhB) photodegradation is further
      investigated. Very interestingly, totally opposite effects were found, that is
      gold tips enhanced photodegradation rate while palladium sulfide tips vastly
      reduced photodegradation. Those phenomena are well explained by our proposed
      mechanism for the charge transfer. This study enables better design of HCs for
      improved photocatalysis and better photovoltaics. 

PMID- 24141380
TI  - Release from herbivory does not confer invasion success for Eugenia uniflora in
      Florida.
AB  - One of the most commonly cited hypotheses explaining invasion success is the
      enemy release hypothesis (ERH), which maintains that populations are regulated by
      coevolved natural enemies where they are native but are relieved of this pressure
      in the new range. However, the role of resident enemies in plant invasion remains
      unresolved. We conducted a field experiment to test predictions of the ERH
      empirically using a system of native, introduced invasive, and introduced non
      invasive Eugenia congeners in south Florida. Such experiments are rarely
      undertaken but are particularly informative in tests of the ERH, as they
      simultaneously identify factors allowing invasive species to replace natives and
      traits determining why most introduced species are unsuccessful invaders. We
      excluded insect herbivores from seedlings of Eugenia congeners where the native
      and invasive Eugenia co-occur, and compared how herbivore exclusion affected
      foliar damage, growth, and survival. We found no evidence to support the ERH in
      this system, instead finding that the invasive E. uniflora sustained
      significantly more damage than the native and introduced species. Interestingly,
      E. uniflora performed better than, or as well as, its congeners in terms of
      growth and survival, in spite of higher damage incidence. Further, although
      herbivore exclusion positively influenced Eugenia seedling survival, there were
      few differences among species and no patterns in regard to invasion status or
      origin. We conclude that the ability of E. uniflora to outperform its native and
      introduced non-invasive congeners, and not release from insect herbivores,
      contributes to its success as an invader in Florida. 

PMID- 24141381
TI  - Strategy of nitrogen acquisition and utilization by carnivorous Dionaea
      muscipula.
AB  - Plant carnivory represents an exceptional means to acquire N. Snap traps of
      Dionaea muscipula serve two functions, and provide both N and photosynthate.
      Using (13)C/(15)N-labelled insect powder, we performed feeding experiments with
      Dionaea plants that differed in physiological state and N status (spring vs.
      autumn plants). We measured the effects of (15)N uptake on light-saturated
      photosynthesis (A(max)), dark respiration (R(D)) and growth. Depending on N
      status, insect capture briefly altered the dynamics of R(D)/A(max), reflecting
      high energy demand during insect digestion and nutrient uptake, followed by
      enhanced photosynthesis and growth. Organic N acquired from insect prey was
      immediately redistributed, in order to support swift renewal of traps and thereby
      enhance probability of prey capture. Respiratory costs associated with permanent
      maintenance of the photosynthetic machinery were thereby minimized. Dionaea's
      strategy of N utilization is commensurate with the random capture of large prey,
      occasionally transferring a high load of organic nutrients to the plant. Our
      results suggest that physiological adaptations to unpredictable resource
      availability are essential for Dionaea's success with regards to a carnivorous
      life style.

PMID- 24141383
TI  - Telomere shortening in liver transplant recipients is not influenced by
      underlying disease or metabolic derangements.
AB  - BACKGROUND: Telomeres are non-coding regions of DNA that cap the ends of
      chromosomes. Their length is considered a marker of human replicative senescence
      and premature aging. Given the high association of liver transplantation with the
      metabolic syndrome, we hypothesized that liver transplant recipients may exhibit
      premature and accelerated aging. MATERIAL AND METHODS: Telomere length in
      peripheral blood lymphocytes was measured by polymerase chain reaction in 62
      consecutive liver-transplant recipients and 59 healthy control subjects aged 20
      76 years. Clinical and laboratory parameters were collected from the medical
      files. RESULTS: The liver transplant recipients were significantly older than the
      control subjects (p=0.012), with significantly higher rates of obesity (BMI >30
      kg/m(2)), dyslipidemia, hypertension, diabetes, and fatty liver. Mean telomere
      length was significantly shorter in the transplant group (0.59+/-0.6 vs. 1.91+/
      1.78 in the controls, p<0.0001). Within the transplant group, there was no
      significant association between mean telomere length and underlying liver disease
      or presence of the metabolic syndrome or its constituents. On multivariate
      analysis, telomere length was negatively associated with patient age (p=0.0001),
      male sex (p=0.04), acute rejection (p=0.005), and fatty liver (p=0.009), and was
      positively associated with time from transplantation (p=0.006). CONCLUSIONS:
      Liver transplantation is associated with shortened telomere length in peripheral
      blood lymphocytes, suggesting accelerated senescence.

PMID- 24141382
TI  - Effects of health insurance on racial disparity in osteoporosis medication
      adherence.
AB  - OBJECTIVE: To explore whether racial disparity in osteoporosis drug therapy
      maintenance varies by health insurance coverage status. DESIGN: Longitudinal
      observation study. SETTING: Cleveland Clinic Health System (Cleveland, OH) from
      January 2006 to December 2009. PATIENTS: 3,901 black and white female Medicare
      beneficiaries starting osteoporosis drug therapy. INTERVENTION: Analysis of the
      health system's integrated electronic medical records. MAIN OUTCOME MEASURES:
      Drug therapy adherence (medication possession ratio >=80%) for more than 12 of 15
      surveillance units and occurrence of extended nonadherence gaps for at least two
      surveillance units in a row. RESULTS: Among patients with supplementary health
      insurance (n = 2,278), no difference was observed for drug therapy adherence ( P
      = 0.17) and extended nonadherence gaps ( P = 0.53) between black and white
      participants. When patients did not have supplementary health insurance (n =
      1,623), blacks (36% [95% CI 28-47]) were less likely to adhere to drug therapy
      than whites (47% [38-57]; odds ratio [OR] 0.34 [95% CI 0.09-0.92], P = 0.004).
      Blacks (25% [19-32]) also were more likely to have an extended nonadherence gap
      episode than whites (18% [11-26]; OR 2.42 [1.13-3.50], P = 0.03). CONCLUSION:
      Similar to previous research on racial disparity in health services, racial
      disparity in osteoporosis drug therapy maintenance between black and white female
      older patients existed when supplementary health insurance was not affordable.

PMID- 24141384
TI  - Freiburg neuropathology case conference: a pineal region tumour in a child.

PMID- 24141385
TI  - Exchange bias of Ni nanoparticles embedded in an antiferromagnetic IrMn matrix.
AB  - The magnetic properties of Ni nanoparticles (Ni-NPs) embedded in an
      antiferromagnetic IrMn matrix were investigated. The Ni-NPs of 8.4 nm mean
      diameter were synthesized by inert gas aggregation. In a second processing step,
      the Ni-NPs were in situ embedded in IrMn films or SiOx films under ultrahigh
      vacuum (UHV) conditions. Findings showed that Ni-NPs embedded in IrMn have an
      exchange bias field HEB = 821 Oe at 10 K, and 50 Oe at 300 K. The extracted value
      of the exchange energy density is 0.06 mJ m(-2) at 10 K, which is in good
      accordance with the results from multilayered thin film systems. The Ni-NPs
      embedded in SiOx did not show exchange bias. As expected for this particle size,
      they are superparamagnetic at T = 300 K. A direct comparison of the Ni-NPs
      embedded in IrMn or SiOx reveals an increase of the blocking temperature from 210
      K to around 400 K. The coercivity of the Ni-NPs exchange coupled to the IrMn
      matrix at 10 K is 8 times larger than the value for Ni-NPs embedded in SiOx. We
      studied time-dependent remanent magnetization at different temperatures. The
      relaxation behavior is described by a magnetic viscosity model which reflects a
      rather flat distribution of energy barriers. Furthermore, we investigated the
      effects of different field cooling processes on the magnetic properties of the
      embedded Ni-NPs. Exchange bias values fit to model calculations which correlate
      the contribution of the antiferromagnetic IrMn matrix to its grain size. 

PMID- 24141386
TI  - Global profiling of carbonyl metabolites with a photo-cleavable isobaric labeling
      affinity tag.
AB  - A carbonyl-reactive photo-cleavable isobaric labeling affinity tag can provide a
      selective, high-throughput, and reproducible approach for the quantitative
      analysis of aldehyde and ketone metabolites in complex biological samples. 

PMID- 24141387
TI  - The kinase mTOR modulates the antibody response to provide cross-protective
      immunity to lethal infection with influenza virus.
AB  - Highly pathogenic avian influenza viruses pose a continuing global threat.
      Current vaccines will not protect against newly evolved pandemic viruses. The
      creation of 'universal' vaccines has been unsuccessful because the immunological
      mechanisms that promote heterosubtypic immunity are incompletely defined. We
      found here that rapamycin, an immunosuppressive drug that inhibits the kinase
      mTOR, promoted cross-strain protection against lethal infection with influenza
      virus of various subtypes when administered during immunization with influenza
      virus subtype H3N2. Rapamycin reduced the formation of germinal centers and
      inhibited class switching in B cells, which yielded a unique repertoire of
      antibodies that mediated heterosubtypic protection. Our data established a
      requirement for the mTORC1 complex in B cell class switching and demonstrated
      that rapamycin skewed the antibody response away from high-affinity variant
      epitopes and targeted more conserved elements of hemagglutinin. Our findings have
      implications for the design of a vaccine against influenza virus. 

PMID- 24141388
TI  - Specification of type 2 innate lymphocytes by the transcriptional determinant
      Gfi1.
AB  - Type 2 innate lymphoid cells (ILC2 cells) participate in host defense against
      helminth parasites and in allergic inflammation. Given their functional
      relatedness to type 2 helper T cells (T(H)2 cells), we explored whether Gfi1 acts
      as a shared transcriptional determinant in ILC2 cells. Gfi1 promoted the
      development of ILC2 cells and controlled their responsiveness during infection
      with Nippostrongylus brasiliensis and protease allergen-induced lung
      inflammation. Gfi1 'preferentially' regulated the responsiveness of ILC2 cells to
      interleukin 33 (IL-33) by directly activating Il1rl1, which encodes the IL-33
      receptor (ST2). Loss of Gfi1 in activated ILC2 cells resulted in impaired
      expression of the transcription factor GATA-3 and a dysregulated genome-wide
      effector state characterized by coexpression of IL-13 and IL-17. Our findings
      establish Gfi1 as a shared determinant that reciprocally regulates the type 2 and
      IL-17 effector states in cells of the innate and adaptive immune systems.

PMID- 24141389
TI  - Risk of childhood overweight or obesity associated with excessive weight gain
      during pregnancy: a meta-analysis.
AB  - PURPOSE: Several investigations have shown that the risk of childhood overweight
      and obesity may be associated with excessive gestational weight gain (GWG), but
      the study samples were limited and results were mixed; hence we conducted this
      meta-analysis to assess the explicit association between them and present
      evidence. METHODS: We searched PubMed, EMbase, Ovid, Web of knowledge and
      Cochrane library for relevant studies. Bibliographies from retrieved articles
      were also manually searched. Cohort studies that presented results by OR or RR
      with 95 % CI for the association of maternal excessive GWG and child
      overweight/obesity were included. The pooled estimates were calculated by fixed
      effect model or random-effect model according to the heterogeneity. RESULTS:
      Twelve cohort studies were identified, and the combined OR of excessive GWG and
      childhood overweight/obesity was 1.33 (95 % CI 1.18-1.50) with evidence of
      heterogeneity (P = 0.000, I (2) = 71.1 %). Adjustment of maternal BMI,
      investigation area, age of children, research type, and omission of any single
      study had little effect on the pooled estimate. After eliminating the effect of
      publication bias by trim and fill analyses, the result still remained
      statistically significant (OR 1.21, 95 % CI 1.05-1.40). CONCLUSIONS: This meta
      analysis suggests that the risk of childhood overweight/obesity is significantly
      associated with excessive gestational weight gain.

PMID- 24141390
TI  - High-efficiency headspace sampling of volatile organic compounds in explosives
      using capillary microextraction of volatiles (CMV) coupled to gas chromatography
      mass spectrometry (GC-MS).
AB  - A novel geometry configuration based on sorbent-coated glass microfibers packed
      within a glass capillary is used to sample volatile organic compounds,
      dynamically, in the headspace of an open system or in a partially open system to
      achieve quantitative extraction of the available volatiles of explosives with
      negligible breakthrough. Air is sampled through the newly developed sorbent
      packed 2 cm long, 2 mm diameter capillary microextraction of volatiles (CMV) and
      subsequently introduced into a commercially available thermal desorption probe
      fitted directly into a GC injection port. A sorbent coating surface area of ~5 *
      10(-2) m(2) or 5,000 times greater than that of a single solid-phase
      microextraction (SPME) fiber allows for fast (30 s), flow-through sampling of
      relatively large volumes using sampling flow rates of ~1.5 L/min. A direct
      comparison of the new CMV extraction to a static (equilibrium) SPME extraction of
      the same headspace sample yields a 30 times improvement in sensitivity for the
      CMV when sampling nitroglycerine (NG), 2,4-dinitrotoluene (2,4-DNT), and
      diphenylamine (DPA) in a mixture containing a total mass of 500 ng of each
      analyte, when spiked into a liter-volume container. Calibration curves were
      established for all compounds studied, and the recovery was determined to be ~1 %
      or better after only 1 min of sampling time. Quantitative analysis is also
      possible using this extraction technique when the sampling temperature, flow
      rate, and time are kept constant between calibration curves and the sample.

PMID- 24141391
TI  - Dielectric properties and Raman spectra of ZnO from a first principles finite
      differences/finite-fields approach.
AB  - Using first principles calculations based on density functional theory and a
      coupled finite-fields/finite-differences approach, we study the dielectric
      properties, phonon dispersions and Raman spectra of ZnO, a material whose
      internal polarization fields require special treatment to correctly reproduce the
      ground state electronic structure and the coupling with external fields. Our
      results are in excellent agreement with existing experimental measurements and
      provide an essential reference for the characterization of crystallinity,
      composition, piezo- and thermo-electricity of the plethora of ZnO-derived
      nanostructured materials used in optoelectronics and sensor devices. 

PMID- 24141392
TI  - Sagittal view of the tibial attachment of the anterior cruciate ligament on
      magnetic resonance imaging and the relationship between anterior cruciate
      ligament size and the physical characteristics of patients.
AB  - BACKGROUND: It is necessary to create bone tunnels within the native footprint
      during anatomic anterior cruciate ligament (ACL) reconstruction. Predicting the
      size of the ACL preoperatively may be useful in order to determine the diameter
      of the bone tunnels preoperatively or during surgery. The tibial insertion site
      of the ACL includes a depressed area, the ACL fovea, which is generally observed
      in the sagittal view on magnetic resonance imaging (MRI). The purposes of this
      study were to measure the anteroposterior diameter of the ACL fovea in the
      sagittal view on MRI and to investigate its associations with the physical
      characteristics of patients. METHODS: One hundred patients (100 knees; 50 males
      and 50 females; mean age, 33 years) were included in this study. The
      anteroposterior diameter of the ACL fovea was measured in the sagittal view on
      MRI. The relationships between the diameter of the ACL fovea and physical
      characteristics including height, weight, and body mass index (BMI) were
      analyzed. RESULTS: The mean diameter of the ACL fovea was 16.1 mm in male
      patients and 14.3 mm in female patients, which were comparable to the previously
      reported values. There were significant positive correlations between the
      diameter of the ACL fovea and height and weight, but not BMI. The number of knees
      in which the diameter of the ACL fovea was <13 mm was 14 (14 %), and females were
      more likely to have ACL fovea diameter <13 mm. CONCLUSIONS: The study indicated
      that it is possible to predict the size of the ACL before surgery by measuring
      the diameter of the ACL fovea on MRI. Physical characteristics of patients
      correlated with the diameter of the ACL fovea. Especially in female patients, it
      is important to consider the size of the ACL preoperatively.

PMID- 24141393
TI  - Correlation of clinical examination, ultrasound sonography, and magnetic
      resonance imaging findings with arthroscopic findings in relation to acute and
      chronic lateral meniscus injuries.
AB  - PURPOSE: The aim of this study was to evaluate whether ultrasound sonography
      (USS) performed by orthopedic surgeons is a reliable method of investigating
      lateral meniscus (LM) knee lesions as compared to magnetic resonance imaging
      (MRI), and arthroscopy, which is the gold standard in clinical practice. METHODS:
      In total, 107 patients were involved in this study. They were hospitalized for
      arthroscopy due to LM injury of the knee. Clinical examination (McMurray's,
      Apley's, and joint line tenderness tests), USS, and MRI were performed prior to
      arthroscopy. We compared the results of clinical examination, USS, and MRI with
      the arthroscopic findings for the knee, which were considered the reference
      values. RESULTS: McMurray's clinical test, which is the most sensitive method of
      detecting lateral meniscus lesions, gave the same sensitivity rate for both acute
      and chronic LM injuries: 65%. USS was observed to be more sensitive and specific
      for chronic LM injuries (85 and 90%, respectively) than for acute LM injuries (71
      and 87%). MRI also yielded higher values of sensitivity and specificity for
      chronic lateral meniscus injuries (75 and 95%, respectively) than for acute LM
      injuries (68 and 87%). CONCLUSIONS: The accuracy of ultrasound examination is
      demonstrated by the high reliability of this method in the diagnosis of lateral
      meniscus lesions of the knee, and the evaluation performed in this study showed
      that ultrasound is a useful clinical tool for diagnosing knee pathology.

PMID- 24141394
TI  - Computational study of the blood flow in three types of 3D hollow fiber membrane
      bundles.
AB  - The goal of this study is to develop a computational fluid dynamics (CFD)
      modeling approach to better estimate the blood flow dynamics in the bundles of
      the hollow fiber membrane based medical devices (i.e., blood oxygenators,
      artificial lungs, and hemodialyzers). Three representative types of arrays,
      square, diagonal, and random with the porosity value of 0.55, were studied. In
      addition, a 3D array with the same porosity was studied. The flow fields between
      the individual fibers in these arrays at selected Reynolds numbers (Re) were
      simulated with CFD modeling. Hemolysis is not significant in the fiber bundles
      but the platelet activation may be essential. For each type of array, the average
      wall shear stress is linearly proportional to the Re. For the same Re but
      different arrays, the average wall shear stress also exhibits a linear dependency
      on the pressure difference across arrays, while Darcy's law prescribes a power
      law relationship, therefore, underestimating the shear stress level. For the same
      Re, the average wall shear stress of the diagonal array is approximately 3.1,
      1.8, and 2.0 times larger than that of the square, random, and 3D arrays,
      respectively. A coefficient C is suggested to correlate the CFD predicted data
      with the analytical solution, and C is 1.16, 1.51, and 2.05 for the square,
      random, and diagonal arrays in this paper, respectively. It is worth noting that
      C is strongly dependent on the array geometrical properties, whereas it is weakly
      dependent on the flow field. Additionally, the 3D fiber bundle simulation results
      show that the three-dimensional effect is not negligible. Specifically, velocity
      and shear stress distribution can vary significantly along the fiber axial
      direction.

PMID- 24141395
TI  - Sniffing out acute kidney injury in the ICU: do we have the tools?
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) is one of the most common
      complications of critical illnesses, and early detection of AKI can improve its
      outcome. Using advanced electronic surveillance tools has attracted attention in
      recent years. RECENT FINDINGS: It is not a secret that information overload in
      clinical practice, particularly those that are admitted to ICUs, can decrease the
      ability of practitioners to identify changes in patients' status in a timely
      manner. On the contrary, knowing the impact of an early and accurate diagnosis of
      syndromes, such as AKI, on patients' outcomes makes the use of electronic
      syndromic surveillance (ESS) tools a mandate. In recent years, a number of such
      tools for early detection of AKI have been developed with variable sensitivity
      and specificity. Although the impact of using these tools on patients' outcomes
      is unclear, the time to the appropriate processes required for the care of AKI
      has been successfully shortened by the use of these devices. SUMMARY: ESS tools
      (sniffers) for AKI may allow improvement in patient processes of care or more
      efficient patient recruitment in AKI-related ICU studies.

PMID- 24141396
TI  - Neurosurgery(r) launches High Impact Manuscript Services (HIMS) program.

PMID- 24141397
TI  - Anatomic risk factors for middle cerebral artery aneurysm rupture: computed
      tomography angiography study of 1009 consecutive patients.
AB  - BACKGROUND: The middle cerebral artery (MCA) is the most frequent location for
      unruptured intracranial aneurysms. Controversy remains as to which unruptured MCA
      aneurysms should be treated prophylactically. OBJECTIVE: To identify independent
      topographical and morphological variables that could predict increased rupture
      risk of MCA aneurysms. METHODS: A retrospective analysis of computed tomography
      angiography data of 1009 consecutive patients with 1309 MCA aneurysms, referred
      between 2000 and 2009 to Helsinki University Hospital, was carried out.
      Morphological and topographical parameters examined for MCA aneurysms comprised
      aneurysm wall regularity, size, neck width, aspect ratio, bottleneck factor,
      height-width ratio, location along the MCA, side, distance from the internal
      carotid artery bifurcation, and dome projection in axial and coronal computed
      tomography angiography views. Univariate and multivariate logistic regression
      analyses were performed to determine independent risk factors for rupture.
      RESULTS: Of the 1309 MCA aneurysms, 69% were unruptured and 31% were ruptured.
      Most unruptured MCA aneurysms were smaller than 7 mm (78%), with a smooth wall
      (80%) and a height-width ratio of 1 (47%) and were located at the main
      bifurcation (57%). Ruptured MCA aneurysms, mostly 7 to 14 mm in size (55%), had
      an irregular wall (78%) and a height-width ratio greater than 1 (72%) and were
      located at the main bifurcation (77%). Thirty-eight percent of MCA bifurcation
      aneurysms, 74% of large aneurysms, 64% of aneurysms with an irregular wall, and
      49% of aneurysms with a height-width ratio greater than 1 were ruptured.
      CONCLUSION: Location at the main MCA bifurcation, wall irregularity, and less
      spherical geometry were independently associated with rupture of MCA aneurysms
      with a correlation with aneurysm size. artery.

PMID- 24141398
TI  - Journal club: role of endoscopic third ventriculostomy and ventriculoperitoneal
      shunt in idiopathic normal pressure hydrocephalus: preliminary results of a
      randomized clinical trial.

PMID- 24141399
TI  - Response to journal club: role of endoscopic third ventriculostomy and
      ventriculoperitoneal shunt in idiopathic normal pressure hydrocephalus:
      preliminary results of a randomized clinical trial.

PMID- 24141401
TI  - Comparative cost-effectiveness analysis of sacral anterior root stimulation for
      rehabilitation of bladder dysfunction in spinal cord injured patients.

PMID- 24141404
TI  - The effects of inflammatory cytokines on lymphatic endothelial barrier function.
AB  - Proper lymphatic function is necessary for the transport of fluids,
      macromolecules, antigens and immune cells out of the interstitium. The lymphatic
      endothelium plays important roles in the modulation of lymphatic contractile
      activity and lymph transport, but it's role as a barrier between the lymph and
      interstitial compartments is less well understood. Alterations in lymphatic
      function have long been associated with edema and inflammation although the
      integrity of the lymphatic endothelial barrier during inflammation is not well
      defined. In this paper we evaluated the integrity of the lymphatic barrier in
      response to inflammatory stimuli commonly associated with increased blood
      endothelial permeability. We utilized in vitro assays of lymphatic endothelial
      cell (LEC) monolayer barrier function after treatment with different inflammatory
      cytokines and signaling molecules including TNF-alpha, IL-6, IL-1beta, IFN-gamma
      and LPS. Moderate increases in an index of monolayer barrier dysfunction were
      noted with all treatments (20-60 % increase) except IFN-gamma which caused a
      greater than 2.5-fold increase. Cytokine-induced barrier dysfunction was blocked
      or reduced by the addition of LNAME, except for IL-1beta and LPS treatments,
      suggesting a regulatory role for nitric oxide. The decreased LEC barrier was
      associated with modulation of both intercellular adhesion and intracellular
      cytoskeletal activation. Cytokine treatments reduced the expression of VE
      cadherin and increased scavenging of beta-catenin in the LECs and this was
      partially reversed by LNAME. Likewise the phosphorylation of myosin light chain
      20 at the regulatory serine 19 site, which accompanied the elevated monolayer
      barrier dysfunction in response to cytokine treatment, was also blunted by LNAME
      application. This suggests that the lymphatic barrier is regulated during
      inflammation and that certain inflammatory signals may induce large increases in
      permeability. 

PMID- 24141405
TI  - Interferon-gamma produced by tumor-infiltrating NK cells and CD4+ T cells
      downregulates TNFSF15 expression in vascular endothelial cells.
AB  - Endothelial cells in an established vasculature secrete tumor necrosis factor
      superfamily-15 (TNFSF15; VEGI; TL1A) that functions as a negative modulator of
      neovascularization to maintain blood vessel stability. TNFSF15 gene expression
      diminishes at angiogenesis and inflammation sites such as in cancers and wounds.
      We reported previously that vascular endothelial growth factor and monocyte
      chemotactic protein-1 contribute to TNFSF15 downmodulation in ovarian cancer.
      Here we show that interferon-gamma (IFNgamma) suppresses TNFSF15 expression in
      human umbilical vein endothelial cells. This activity is mediated by IFNgamma
      receptor and the transcription factor STAT1. Immunohistochemical analysis of
      ovarian cancer clinical specimens indicates that TNFSF15 expression diminishes
      while tumor vascularity increases in specimens with high-grades of IFNgamma
      expression. Since tumor-infiltrating NK and CD4(+) T cells are the main sources
      of IFNgamma in tumor lesions, we isolated these cells from peripheral blood of
      healthy individuals, treated the cells with ovarian cancer OVCAR3 cell
      conditioned media, and found a onefold and tenfold increase of IFNgamma
      production in NK and CD4(+) T cells, respectively, compared with that in vehicle
      treated cells. These findings support the view that tumor-infiltrating NK and
      CD4(+) T cells under the influence of cancer cells significantly increase the
      production of IFNgamma, which in turn inhibits TNFSF15 expression in vascular
      endothelial cells, shifting the balance of pro- and anti-angiogenic factors
      toward escalated angiogenesis potential in the tumor. 

PMID- 24141406
TI  - Synthesis of biomimetic oxygen-carrying compartmentalized microparticles using
      flow lithography.
AB  - We report a microfluidic approach for lithographically photo-patterning
      compartmentalized microparticles with any 2D-extruded shape, down to the cellular
      length scale (~10 microns). The prepolymer solution consists of a UV
      crosslinkable perfluorodecalin-in-water nanoemulsion stabilized by Pluronic((r))
      F-68. The nanoemulsions are generated using high-pressure homogenization and are
      osmotically stabilized by the trapped species method. The presence of PFC
      droplets increases the solubility and diffusivity of oxygen in the prepolymer
      solution, thereby enhancing the rate of O2 inhibition during microparticle
      synthesis. We develop a simple model that successfully predicts the augmented O2
      mass transport, which agrees well with experimental data. Informed by our
      analytical results, cell-sized composite microgels are generated by controlling
      the oxygen environment around the polydimethylsiloxane (PDMS) microfluidic
      synthesis device. These nanoemulsion composites are functionally similar to red
      blood cells as oxygen carriers. Such bio-inspired polymeric particles with
      controlled physical properties are promising vehicles for drug delivery and
      clinical diagnostics. 

PMID- 24141407
TI  - Availability of an assay for detecting Mycobacterium tuberculosis, including
      rifampin-resistant strains, and considerations for its use - United States, 2013.
AB  - In August 2013, the Food and Drug Administration (FDA) permitted marketing of the
      Xpert MTB/RIF assay (Cepheid, Sunnyvale, California) to detect DNA of the
      Mycobacterium tuberculosis complex (MTBC) and genetic mutations associated with
      resistance to rifampin (RMP) in unprocessed sputum and concentrated sputum
      sediments. Along with clinical, radiographic, and other laboratory findings,
      results of the assay aid in the diagnosis of pulmonary tuberculosis (TB). The
      assay is a nucleic acid amplification-based (NAA)* test using a disposable
      cartridge in conjunction with the GeneXpert Instrument System. Sensitivity and
      specificity of the Xpert MTB/RIF assay for detection of MTBC appear to be
      comparable with other FDA-approved NAA assays for this use, although direct
      comparison studies have not been performed. Sensitivity of detection of RMP
      resistance was 95% and specificity 99% in a multicenter study using archived and
      prospective specimens from subjects aged >=18 years suspected of having TB who
      had 0-3 days of antituberculous treatment. CDC continues to recommend following
      published U.S. guidelines for TB diagnosis and infection control practice,
      including the use and interpretation of NAA test results. Providers and
      laboratories need to ensure that specimens are available for other recommended
      mycobacteriological testing. The Xpert MTB/RIF assay aids in the prompt diagnosis
      of TB and RMP-resistant disease. RMP resistance most often coexists with
      isoniazid (INH) resistance; TB that is resistant to both drugs is multidrug
      resistant (MDR)? TB. Because the prevalence of RMP resistance is low in the
      United States (about 1.8% of TB cases), a positive result indicating a mutation
      in the rpoB gene of MTBC should be confirmed by rapid DNA sequencing for prompt
      reassessment of the treatment regimen and followed by growth-based drug
      susceptibility testing (DST). CDC offers these services free of charge.S 

PMID- 24141408
TI  - Chemical constituents of Aspergillus sp EJC08 isolated as endophyte from Bauhinia
      guianensis and their antimicrobial activity.
AB  - The present work reports the isolation of five compounds from Aspergillus sp
      EJC08 isolated as endophytic from Bauhinia guianensis, a tipical plant of the
      Amazon. The compounds ergosterol (1), ergosterol peroxide (2), mevalolactone (3),
      monomethylsulochrin (4) and trypacidin A (5) were isolated by chromatographic
      procedures and identified by spectral methods of 1D and 2D NMR and MS. Compounds
      3, 4 and 5 were tested against Escherichia coli, Pseudomonas aeruginosa, Bacillus
      subtilis and Staphylococcus aureus and showed good activity. 

PMID- 24141409
TI  - Growth and biochemical composition of Chlorella vulgaris in different growth
      media.
AB  - The need for clean and low-cost algae production demands for investigations on
      algal physiological response under different growth conditions. In this research,
      we investigated the growth, biomass production and biochemical composition of
      Chlorella vulgaris using semi-continuous cultures employing three growth media
      (LC Oligo, Chu 10 and WC media). The highest cell density was obtained in LC
      Oligo, while the lowest in Chu medium. Chlorophyll a, carbohydrate and protein
      concentrations and yield were highest in Chu and LC Oligo media. Lipid class
      analysis showed that hydrocarbons (HC), sterol esthers (SE), free fatty acids
      (FFA), aliphatic alcohols (ALC), acetone mobile polar lipids (AMPL) and
      phospholipids (PL) concentrations and yields were highest in the Chu medium.
      Triglyceride (TAG) and sterol (ST) concentrations were highest in the LC Oligo
      medium. The results suggested that for cost effective cultivation, LC Oligo
      medium is the best choice among those studied, as it saved the cost of buying
      vitamins and EDTA associated with the other growth media, while at the same time
      resulted in the best growth performance and biomass production. 

PMID- 24141410
TI  - Centesimal composition and physical-chemistry analysis of the edible mushroom
      Lentinus strigosus occurring in the Brazilian Amazon.
AB  - The centesimal composition and the physical and chemical analyses of Lentinus
      strigosus, an edible mushroom occurring in the Brazilian Amazon and produced in
      alternative substrates based on wood and agroindustrial residues, were evaluated.
      For this purpose, the C, N, pH, soluble solids, water activity, protein, lipids,
      total fiber, ash, carbohydrate, and energy levels were determined. The substrates
      were formulated from Simarouba amara Aubl. ("marupa"), Ochroma piramidale Cav.
      Ex. Lam. ("pau-de-balsa") and Anacardium giganteum ("cajui") sawdust and Bactris
      gasipaes Kunth ("pupunheira") stipe and Saccharum officinarum (sugar cane
      bagasse). The results indicated that the nutritional composition of L. strigosus
      varied with the substrate of cultivation; the protein levels found in mushrooms
      grown in the different substrates (18-21.5%) varied with the substrate and was
      considered high; the soluble solids present in the mushrooms could have a
      relation with complex B hydrosoluble vitamins. L. strigosus could be considered
      as important food owing to its nutritional characteristics such as high protein
      content, metabolizable carbohydrates and fibers, and low lipids and calories
      content.

PMID- 24141412
TI  - Genetic variation in native and farmed populations of Tambaqui (Colossoma
      macropomum) in the Brazilian Amazon: regional discrepancies in farming systems.
AB  - The tambaqui, Colossoma macropomum, is the most popular fish species used for
      aquaculture in Brazil but there is no study comparing genetic variation among
      native and farmed populations of this species. In the present study, we analyzed
      DNA sequences of the mitochondrial DNA to evaluate the genetic diversity among
      two wild populations, a fry-producing breeding stock, and a sample of fish farm
      stocks, all from the region of Santarem, in the west of the Brazilian state of
      Para. Similar levels of genetic diversity were found in all the samples and
      surprisingly the breeding stock showed expressive representation of the genetic
      diversity registered on wild populations. These results contrast considerably
      with those of the previous study of farmed stocks in the states of Amapa, Para,
      Piaui, and Rondonia, which recorded only two haplotypes, indicating a long
      history of endogamy in the breeding stocks used to produce fry. The results of
      the two studies show two distinct scenarios of tambaqui farming in the Amazon
      basin, which must be better evaluated in order to guarantee the successful
      expansion of this activity in the region, and the rest of Brazil, given that the
      tambaqui and its hybrids are now farmed throughout the country. 

PMID- 24141413
TI  - Evaluation of chemical constituents and antioxidant activity of coconut water
      (Cocus nucifera L.) and caffeic acid in cell culture.
AB  - Coconut water contains several uncharacterized substances and is widely used in
      the human consumption. In this paper we detected and quantified ascorbic acid and
      caffeic acid and total phenolics in several varieties of coconut using HPLS/MS/MS
      (25.8 +/- 0.6 ug/mL and 1.078 +/- 0.013 ug/mL and 99.7 ug/mL, respectively, in
      the green dwarf coconut water, or 10 mg and 539 ug and 39.8 mg for units of
      coconut consumed, 500 +/- 50 mL). The antioxidant potential of four coconut
      varieties (green dwarf, yellow dwarf, red dwarf and yellow Malaysian) was
      compared with two industrialized coconut waters and the lyophilized water of the
      green dwarf variety. All varieties were effective in scavenging the DPPH radical
      (IC50=73 uL) and oxide nitric (0.1 mL with an IP of 29.9%) as well as in
      inhibiting the in vitro production of thiobarbituric acid reactive substances (1
      mL with an IP of 34.4%), highlighting the antioxidant properties of the green
      dwarf which it is the most common used. In cell culture, the green dwarf water
      was efficient in protecting against oxidative damages induced by hydrogen
      peroxide.

PMID- 24141415
TI  - Transmission rate variation among three B chromosome variants in the fish
      Prochilodus lineatus (Characiformes, Prochilodontidae).
AB  - Cytogenetic studies were developed in Prochilodus lineatus (Valenciennes 1836),
      describing an interesting system of small supernumerary chromosomes. The purpose
      of this work is to study the frequency and morphology of B chromosomes in
      individuals from the parental line and the inheritance patterns of these elements
      in individuals obtained from controlled crosses in the species P. lineatus. The
      transmission rate of B chromosomes revealed a k(B)=0.388 for the acrocentric
      type, a kB=0.507 for the metacentric type and a k(B)=0.526 for the submetacentric
      type. The obtained results raise hypothesis that B-acrocentric chromosomes are
      involved in an extinction process in this species, while the metacentric and
      submetacentric supernumerary elements comprises a neutral mechanism and follows a
      Mendelian transmission rate.

PMID- 24141416
TI  - Effect of environmental factors on the abundance of decapod crustaceans from soft
      bottoms off southeastern Brazil.
AB  - This study investigated the importance of variations in environmental factors
      affecting the abundance patterns of decapods on the southeastern Brazilian coast.
      Sampling was carried out monthly from January 1998 through December 1999 in
      Ubatumirim and Mar Virado, Ubatuba region, using a commercial shrimp fishing boat
      equipped with double-rig nets. Six areas adjacent to rocky shores were chosen.
      Bottom-water samples were collected using a Nansen bottle, to measure the
      temperature and salinity. Sediment samples were also obtained by means of a Van
      Veen grab, for determination of texture and organic-matter content. The
      association of environmental factors with species abundance was evaluated by
      Canonical Correspondence Analysis (alpha = 0.05). Forty-one species of Decapoda
      were used in the multivariate analysis. The analysis indicated that sediment
      texture (phi) and bottom temperature were the main factors correlated (p < 0.05)
      with the spatial and temporal abundance of the species. Considering the study
      region as faunal transition zone, including a mixture of species of both tropical
      and subantarctic origin, the species responded differently to environmental
      factors, mainly temperature. It is conceivable that the decapods adjust their
      distribution according to their intrinsic physiological limitations, possibly as
      a result of the available resources. 

PMID- 24141417
TI  - Preliminary phytochemical screening and molluscicidal activity of the aqueous
      extract of Bidens pilosa Linne (Asteraceae) in Subulina octona (Mollusca,
      Subulinidade).
AB  - The aim of this study was to establish reference concentrations (LC50 e LC90) of
      aqueous extracts of Bidens pilosa on the land snail Subulina octona, in order to
      assess the changes caused by 24 and 48 h exposure to the sublethal concentration
      regarding species' fecundity, hatchability and in offspring produced after
      exposure to confirm the presence of tannins, saponins and flavonoids in this
      plant species. Eggs newly hatched and 30 day-old snails were exposed to sublethal
      concentration, calculated for adults. The phytochemical analysis confirmed the
      presence of flavonoids, condensed tannins and saponins in the aqueous extract of
      B. pilosa. The LC50 and LC90 obtained were 51.4 mg/mL and 74.1 mg/mL
      respectively. The exposure to sublethal concentration reduced significantly the
      hatchability and the survival of the offspring hatched from exposed eggs and also
      caused a reduction on survival and growth in snails exposed for both time period.
      The exposure time also caused a reduction at the evaluated parameters.

PMID- 24141418
TI  - Protein A immunosensor for the detection of immunoglobulin G by impedance
      spectroscopy.
AB  - A novel highly sensitive electrochemical impedimetric Protein A immunosensor for
      the determination of immunoglobulin G (IgG) was developed by immobilization of
      Protein A within a newly synthesized, and characterized polymer,
      poly(maleicanhydride-alt-decene-1). TiO2 nanoparticles (10-30 nm) were
      synthesized, characterized with X-ray diffraction, transmission electron
      microscopy and Brunauer-Emmett-Teller surface analysis. The electron transfer
      between IgG and the poly(maleicanhydride-alt-decene-1)-TiO2-Protein A is
      quasireversible with a formal potential of 225 mV vs Ag|AgCl. The response of the
      poly(maleicanhydride-alt-decene-1)-TiO2-Protein A immunosensor was proportional
      to IgG concentration with a correlation coefficient of 0.9963. The detection
      limit and linear range was 0.57 ng mL(-1) and 0.0062-500 MUg mL(-1),
      respectively. Impedance measurments showed that synthesized TiO2 nanoparticles
      have better conducting properties compared with commercial degussa P25 TiO2
      nanoparticles. The nonspecific binding of anti-MBP was 10 %. The label-free
      impedimetric immunosensor provided a simple and sensitive detection method for
      the specific determination of IgG in human serum. 

PMID- 24141419
TI  - Manipulation of culture strategies to enhance capsaicin biosynthesis in
      suspension and immobilized cell cultures of Capsicum chinense Jacq. cv. Naga King
      Chili.
AB  - Manipulation of culture strategies was adopted to study the influence of nutrient
      stress, pH stress and precursor feeding on the biosynthesis of capsaicin in
      suspension and immobilized cell cultures of C. chinense. Cells cultured in the
      absence of one of the four nutrients (ammonium and potassium nitrate for nitrate
      and potassium stress, potassium dihydrogen orthophosphate for phosphorus stress,
      and sucrose for sugar stress) influenced the accumulation of capsaicin. Among the
      stress factors studied, nitrate stress showed maximal capsaicin production on day
      20 (505.9 +/- 2.8 MUg g(-1) f.wt) in immobilized cell, whereas in suspension
      cultures the maximum accumulation (345.5 +/- 2.9 MUg g(-1) f.wt) was obtained on
      day 10. Different pH affected capsaicin accumulation; enhanced accumulation of
      capsaicin (261.6 +/- 3.4 MUg g(-1) f.wt) was observed in suspension cultures at
      pH 6 on day 15, whereas in case of immobilized cultures the highest capsaicin
      content (433.3 +/- 3.3 MUg g(-1) f.wt) was obtained at pH 5 on day 10. Addition
      of capsaicin precursors and intermediates significantly enhanced the biosynthesis
      of capsaicin, incorporation of vanillin at 100 MUM in both suspension and
      immobilized cell cultures resulted in maximum capsaicin content with 499.1 +/-
      5.5 MUg g(-1) f.wt on day 20 and 1,315.3 +/- 10 MUg g(-1) f.wt on day 10,
      respectively. Among the different culture strategies adopted to enhance capsaicin
      biosynthesis in cell cultures of C. chinense, cells fed with vanillin resulted in
      the maximum capsaicin accumulation. The rate of capsaicin production was
      significantly higher in immobilized cells as compared to freely suspended cells.

PMID- 24141420
TI  - Notch1-dependent regulation of p27 determines cell fate in colorectal cancer.
AB  - Enhanced Notch signaling contributes to uncontrolled cell growth and cell death
      resistance in cancer. Here, we demonstrate that in colorectal carcinoma cells the
      Notch1-dependent activation of cell cycle and proliferation is mediated by
      repression of the cyclin-dependent kinase inhibitor (CDKI) p27. The half-life of
      p27 significantly increased after siRNA-mediated knockdown of Notch1. Notch1
      depletion altered the transcription of SKP2, KPC1 and KPC2, which are E3
      ubiquitin ligase subunits targeting p27 for proteasomal degradation in the
      nucleus and the cytoplasm, respectively. As a consequence, the levels of p27 in
      both cellular fractions were elevated upon Notch1 knockdown. Importantly, the
      downregulation of Notch1 significantly sensitized colorectal cancer cells to
      chemotherapy and ionizing radiation. Our findings support an important role of
      p27 in Notch1-dependent oncogenic signaling and suggest that Notch1 is a
      promising target for an experimental therapy of colorectal carcinoma. 

PMID- 24141421
TI  - Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2.
AB  - Here we show that Mst1, a proapoptotic kinase, impairs protein quality control
      mechanisms in the heart through inhibition of autophagy. Stress-induced
      activation of Mst1 in cardiomyocytes promoted accumulation of p62 and aggresome
      formation, accompanied by the disappearance of autophagosomes. Mst1
      phosphorylated the Thr108 residue in the BH3 domain of Beclin1, which enhanced
      the interaction between Beclin1 and Bcl-2 and/or Bcl-xL, stabilized the Beclin1
      homodimer, inhibited the phosphatidylinositide 3-kinase activity of the Atg14L
      Beclin1-Vps34 complex and suppressed autophagy. Furthermore, Mst1-induced
      sequestration of Bcl-2 and Bcl-xL by Beclin1 allows Bax to become active, thereby
      stimulating apoptosis. Mst1 promoted cardiac dysfunction in mice subjected to
      myocardial infarction by inhibiting autophagy, associated with increased levels
      of Thr108-phosphorylated Beclin1. Moreover, dilated cardiomyopathy in humans was
      associated with increased levels of Thr108-phosphorylated Beclin1 and signs of
      autophagic suppression. These results suggest that Mst1 coordinately regulates
      autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a
      three-way interaction among Bcl-2 proteins, Beclin1 and Bax. 

PMID- 24141424
TI  - Short course of cognitive behavioural therapy may reduce health anxiety, say
      researchers.

PMID- 24141425
TI  - Angels' share challenge.

PMID- 24141422
TI  - Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology.
AB  - Fragile X syndrome (FXS), the most common cause of inherited mental retardation
      and autism, is caused by transcriptional silencing of FMR1, which encodes the
      translational repressor fragile X mental retardation protein (FMRP). FMRP and
      cytoplasmic polyadenylation element-binding protein (CPEB), an activator of
      translation, are present in neuronal dendrites, are predicted to bind many of the
      same mRNAs and may mediate a translational homeostasis that, when imbalanced,
      results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double
      knockout mice displayed amelioration of biochemical, morphological,
      electrophysiological and behavioral phenotypes associated with FXS. Acute
      depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice rescued working
      memory deficits, demonstrating reversal of this FXS phenotype. Finally, we find
      that FMRP and CPEB1 balance translation at the level of polypeptide elongation.
      Our results suggest that disruption of translational homeostasis is causal for
      FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary
      for normal neurologic function. 

PMID- 24141423
TI  - Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing
      Claudin-1 overexpression in podocytes.
AB  - Sirtuin 1 (Sirt1), a NAD(+)-regulated deacetylase with numerous known positive
      effects on cellular and whole-body metabolism, is expressed in the renal cortex
      and medulla. It is known to have protective effects against age-related disease,
      including diabetes. Here we investigated the protective role of Sirt1 in diabetic
      renal damage. We found that Sirt1 in proximal tubules (PTs) was downregulated
      before albuminuria occurred in streptozotocin-induced or obese (db/db) diabetic
      mice. PT-specific SIRT1 transgenic and Sirt1 knockout mice showed prevention and
      aggravation of the glomerular changes that occur in diabetes, respectively, and
      nondiabetic knockout mice exhibited albuminuria, suggesting that Sirt1 in PTs
      affects glomerular function. Downregulation of Sirt1 and upregulation of the
      tight junction protein Claudin-1 by SIRT1-mediated epigenetic regulation in
      podocytes contributed to albuminuria. We did not observe these phenomena in 5/6
      nephrectomized mice. We also demonstrated retrograde interplay from PTs to
      glomeruli using nicotinamide mononucleotide (NMN) from conditioned medium,
      measurement of the autofluorescence of photoactivatable NMN and injection of
      fluorescence-labeled NMN. In human subjects with diabetes, the levels of SIRT1
      and Claudin-1 were correlated with proteinuria levels. These results suggest that
      Sirt1 in PTs protects against albuminuria in diabetes by maintaining NMN
      concentrations around glomeruli, thus influencing podocyte function. 

PMID- 24141426
TI  - Solution to the pycnometer challenge.

PMID- 24141427
TI  - On the chemical reactions of carbon dioxide isoelectronic molecules CS2 and OCS
      with 1-butyl-3-methylimidazolium acetate.
AB  - Raman and NMR spectroscopies show that CS2 and OCS react spontaneously with 1
      butyl-3-methylimidazolium acetate [C4mim] [Ac] in the liquid phase. The formation
      of [C4mim] CO2, [C4mim] COS, CH3COS(-) and gaseous CO2 and OCS in both systems
      demonstrates that the anion plays an unexpected role not observed in the CO2
      [C4mim] [Ac] reaction. 

PMID- 24141428
TI  - Development and initial testing of messages to encourage tuberculosis testing and
      treatment among Bacille Calmette-Guerin (BCG) vaccinated persons.
AB  - Misperceptions surrounding the Bacille Calmette-Guerin (BCG) vaccine can lead
      some vaccinated individuals to resist being tested and treated for tuberculosis
      (TB). Educational messages to best explain the risk of TB to BCG-vaccinated,
      Hispanic persons were systematically developed and tested. First, TB program
      staff provided messages they considered effective. These were analyzed and
      validated by TB experts, and then presented in group interviews initially to
      foreign-born Hispanic persons with a TB diagnosis, and then persons without a
      prior TB diagnosis. Based on interviewees' feedback, preferred statements were
      used to develop one long and three short comprehensive messages. One-on-one
      interviews were conducted with Hispanic persons to assess the saliency of the
      comprehensive educational messages. Participants preferred messages that were
      gain or positively-framed and explained that BCG does not confer lifelong
      protection against TB. Participants confirmed the messages would likely have a
      positive impact on patient decisions to undergo TB testing and treatment. 

PMID- 24141429
TI  - [Aquagenic urticaria. A case report].
AB  - A 38-year-old woman presented with recurrent episodes of urticaria after contact
      with water affecting the upper part of the body. We confirmed the diagnosis of
      aquagenic urticaria. Aquagenic urticaria is a rare form of contact urticaria with
      small wheals generally affecting the upper part of the body. It has to be
      distinguished from aquagenic pruritus. The pathogenetic mechanisms are not known
      in detail. Treatment with antihistamines, ultraviolet therapy or application of
      protective hydrophobic barrier creams could be effective. 

PMID- 24141430
TI  - [Allergen-specific immunotherapy for atopic dermatitis].

PMID- 24141431
TI  - [The International Classification of Diseases, the Family of International
      Classifications, the ICD-11, and post-polio syndrome].
AB  - The first International Classification of Diseases (ICD) was approved in 1893 and
      since then it has been periodically reviewed. The last, 10th revision (ICD-10),
      was approved in 1989. Since 1989, it was possible to update from ICD revisions,
      which did not happen before. The next revision (ICD-11) would probably be
      published in 2015. In 1989, mechanisms were established to update ICD-10, through
      the creation of the Morbidity Reference Group (MbRG) in 1997 and the Update and
      Revision Committee (URC) in 2000. The Morbidity Reference Group (MbRG) was
      created in 2007 to discuss in more detail the issues to update morbidity. A
      specific code in ICD was not included in the revision of ICD-10 in 1989 for the
      post-polio syndrome (PPS). However, the ICD new code G14 for PPS was included in
      ICD-10 since 2010. 

PMID- 24141432
TI  - Multiple sclerosis in the Southern and Northern hemispheres: the month of birth
      at different latitudes has the same influence on the prevalence and progression
      of the disease in the Northern and Southern hemispheres?

PMID- 24141433
TI  - Changes in normal appearing spinal cord in multiple sclerosis: another brick in
      the wall.

PMID- 24141435
TI  - Diffusion tensor magnetic resonance imaging may show abnormalities in the normal
      appearing cervical spinal cord from patients with multiple sclerosis.
AB  - OBJECTIVE: This study aims to evaluate "in vivo" the integrity of the normal
      appearing spinal cord (NASC) in patients with multiple sclerosis (MS) compared to
      controls, using diffusion tensor MR imaging. METHODS: We studied 32 patients with
      MS and 17 without any neurologic disorder. Fractional anisotropy (FA), axial
      diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were
      calculated within regions of interest at C2 and C7 levels in the four columns of
      the spinal cord. RESULTS: At C2, FA value was decreased in MS patients. Besides,
      RD value was higher in MS than in controls. At C7, MD values were increased in
      MS. CONCLUSION: The NASC in the right column of the cervical spinal cord showed
      abnormal FA, RD and MD values, which is possibly related to demyelination, since
      the FA abnormality was related to the RD and not to the AD.

PMID- 24141434
TI  - Multiple sclerosis in South America: month of birth in different latitudes does
      not seem to interfere with the prevalence or progression of the disease.
AB  - OBJECTIVE: To assess whether the month of birth in different latitudes of South
      America might influence the presence or severity of multiple sclerosis (MS) later
      in life. METHODS: Neurologists in four South American countries working at MS
      units collected data on their patients' month of birth, gender, age, and disease
      progression. RESULTS: Analysis of data from 1207 MS patients and 1207 control
      subjects did not show any significant variation in the month of birth regarding
      the prevalence of MS in four latitude bands (0-10; 11-20; 21-30; and 31-40
      degrees). There was no relationship between the month of birth and the severity
      of disease in each latitude band. CONCLUSION: The results from this study show
      that MS patients born to mothers who were pregnant at different Southern
      latitudes do not follow the seasonal pattern observed at high Northern latitudes.

PMID- 24141436
TI  - Proton magnetic spectroscopy agreed better with magnetic resonance image to
      lateralization of epileptogenic zone than with surface electroencephalography.
AB  - OBJECTIVE: To analyze the agreement rate of proton magnetic spectroscopy with
      magnetic resonance image (MRI) and surface electroencephalography (EEG) in
      extratemporal neocortical epilepsies. METHODS: A cross-sectional study, type
      series of cases included 33 patients, age range 13-59 years old, of both gender,
      presenting structural alteration identified by MRI (75.8%) or by neurophysiologic
      techniques (72.7%). The variables were alterations of N-acetyl-aspartate/choline,
      N-acetyl-aspartate/creatine, choline/creatine, and N-acetyl-aspartate/cho
      line+creatine coefficient of asymmetry. RESULTS: Agreement rates of
      lateralization by coefficient of asymmetry of NAA/Cho, NAA/Cr, Co/Cr, and
      NAA/Cho+Cr with MRI, independent of alteration of surface EEG, were equal to
      93.3, 57.9, 15.4, and 93.3%, respectively, modifying to 100, 33.3, 0, and 100%,
      in 16 patients, with lateralization agreement of MRI and surface EEG. CONCLUSION:
      Proton magnetic spectroscopy agreed better with MRI to lateralization of
      epileptogenic zone than with surface EEG.

PMID- 24141437
TI  - Urinary dysfunction with detrusor hyperactivity in women with Parkinson's disease
      cannot be blamed as a factor of worsening motor performance.
AB  - INTRODUCTION: Detrusor hyperactivity is the leading cause of urinary dysfunction
      in Parkinson's disease (PD). There are few studies correlating PD clinical
      aspects with this autonomic feature. METHODS: A cohort of 63 women with PD were
      prospectively examined for assessment of clinical aspects and disease severity
      using unified Parkinson's disease rating scale and Hoehn-Yahr scale,
      respectively. The urologic function was evaluated by the urodynamic study. Two
      groups were categorized at this time - groups with and without detrusor
      hyperactivity. After seven years, the same parameters were re-evaluated. RESULTS:
      Progression of the disease on mental scores was found in the group with detrusor
      hyperactivity. On follow-up, clinical symptoms and severity did not show
      significant worsening between the groups. CONCLUSION: Detrusor hyperactivity is a
      frequent urodynamic finding in PD, and even though it is associated with
      dopaminergic dysfunction, it cannot be blamed as a factor of worsening motor
      performance, but is probably associated with poor cognitive and mental prognosis.

PMID- 24141438
TI  - Verbal learning on depressive pseudodementia: accentuate impairment of free
      recall, moderate on learning processes, and spared short-term and recognition
      memory.
AB  - OBJECTIVE: Depressive pseudodementia (DPD) is a clinical condition characterized
      by depressive symptoms followed by cognitive and functional impairment
      characteristics of dementia. Memory complaints are one of the most related
      cognitive symptoms in DPD. The present study aims to assess the verbal learning
      profile of elderly patients with DPD. METHODS: Ninety-six older adults (34 DPD
      and 62 controls) were assessed by neuropsychological tests including the Rey
      auditory-verbal learning test (RAVLT). A multivariate general linear model was
      used to assess group differences and controlled for demographic factors. RESULTS:
      Moderate or large effects were found on all RAVLT components, except for short
      term and recognition memory. CONCLUSION: DPD impairs verbal memory, with large
      effect size on free recall and moderate effect size on the learning. Short-term
      storage and recognition memory are useful in clinical contexts when the
      differential diagnosis is required.

PMID- 24141439
TI  - Neuropathic pain in patients with spinal cord injury: report of 213 patients.
AB  - OBJECTIVE: Management of neuropathic pain following spinal cord injury (SCI) can
      be a frustrating experience for patients since it poses a therapeutic challenge.
      In this article the authors describe the clinical characteristics of a group of
      patients with pain after spinal cord injury. METHODS: In this retrospective
      study, 213 patients with SCI and neuropathic pain were assessed. We analyzed
      clinical characteristics, treatment options, and pain intensity for these
      patients. RESULTS: The main cause of SCI was spine trauma, which occurred in 169
      patients, followed by tumors and infection. Complete lesions were verified in 144
      patients. In our study, patients with traumatic SCI and partial lesions seem to
      be presented with more intense pain; however, this was not statistically
      significant. CONCLUSIONS: Neuropathic pain is a common complaint in patients with
      SCI and presents a treatment challenge. Knowledge of the clinical characteristics
      of this group of patients may help determine the best approach to intervention.

PMID- 24141440
TI  - Improvement of motor function and decreased need for postnatal shunting in
      children who had undergone intrauterine myelomeningocele repair.
AB  - OBJECTIVE: To compare neuromotor development between patients who did and those
      who did not undergo intrauterine myelomeningocele repair. METHODS: Children with
      myelomeningocele aged between 3.5 and 6 years who did undergo intrauterine repair
      (Group A, n=6) or not (Group B; n=7) were assessed for neuromotor development at
      both anatomical and functional levels, need for orthoses, and cognitive function.
      RESULTS: Intrauterine myelomeningocele repair significantly improved motor
      function. The functional level was higher than the anatomical level by 2 or more
      spinal segments in all children in Group A and 2 children in Group B, with a
      significant statistical difference between groups (p<0.05). Five children in
      Group A and one in Group B were community ambulators. CONCLUSION: Despite the
      small sample, it was observed that an improvement of motor function and decreased
      need for postnatal shunting in the 6 children who had undergone intrauterine
      myelomeningocele repair.

PMID- 24141441
TI  - Suboccipital craniectomy with opening of the fourth ventricle and duraplasty:
      study of 192 cases of craniovertebral malformations.
AB  - The prime objective in the surgical treatment of basilar impression (BI), Chiari
      malformation (CM), and/or syringomyelia (SM) is based on restoration of the
      normal cerebrospinal fluid (CSF) dynamics at the craniovertebral junction and
      creation of a large artificial cisterna magna, avoiding the caudal migration of
      the hindbrain. It is observed that a large craniectomy might facilitate an upward
      migration of the posterior fossa structures. There are many surgical techniques
      to decompress the posterior fossa; however, a gold standard approach remains
      unclear. The authors present the results of 192 cases of BI, CM, and SM treated
      between 1975 and 2008 and whose surgical treatment was characterized by a large
      craniectomy without tonsillectomy with the patient in the sitting position, large
      opening of the fourth ventricle, and duraplasty.

PMID- 24141442
TI  - Assessment of gait deviation on the Babinski-Weill test in healthy Brazilians.
AB  - OBJECTIVE: The aim of this study was to validate a simple and reproducible method
      for assessing gait deviation on the Babinski-Weill test in a representative
      sample of healthy Brazilians. METHODS: Gait deviations were measured in 75
      individuals (median=30 years, 41 women) for forward, backwards, and Babinski
      Weill steps. The test entailed blindfolded individuals walking 10 paces at a
      frequency of 1 Hz with deviations subsequently measured by a protractor. RESULTS:
      Mean gait deviation forward was 0.53 degrees  with standard deviation (SD)=4.22
      and backwards was 2.14 degrees  with SD=4.29. No significant difference in
      deviation was detected between genders (t test p=0.40 forward and p=0.77
      backwards) or for age (ANOVA, p=0.33 forward and p=0.63 backwards). On the
      Babinski-Weill test, mean gait deviation was 5.26 degrees ; SD=16.32 in women and
      -3.11 degrees ; SD=12.41 in men, with no significant difference between genders
      (t test, p=0.056). DISCUSSION: Defining normative gait patterns helps distinguish
      pathological states.

PMID- 24141443
TI  - Validation of the Brazilian version of the Clinical Gait and Balance Scale and
      comparison with the Berg Balance Scale.
AB  - OBJECTIVE: To validate the Clinical Gait and Balance Scale (GABS) for a Brazilian
      population of patients with Parkinson's disease (PD) and to compare it to the
      Berg Balance Scale (BBS). METHODS: One hundred and seven PD patients were
      evaluated by shortened UPDRS motor scale (sUPDRSm), Hoehn and Yahr (HY), Schwab
      and England scale (SE), Falls Efficacy Scale International (FES-I), Freezing of
      Gait Questionnaire (FOG-Q), BBS and GABS. RESULTS: The internal consistency of
      the GABS was 0.94, the intra-rater and inter-rater reliability were 0.94 and 0.98
      respectively. The area under the receiver operating characteristic (ROC) curve
      was 0.72, with a sensitivity of 0.75 and specificity of 0.6, to discriminate
      patients with a history of falls in the last twelve months, for a cut-off score
      of 13 points. CONCLUSIONS: Our study shows that the Brazilian version of the GABS
      is a reliable and valid instrument to assess gait and balance in PD.

PMID- 24141444
TI  - The myasthenic patient in crisis: an update of the management in Neurointensive
      Care Unit.
AB  - Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular
      transmission leading to generalized or localized muscle weakness due most
      frequently to the presence of autoantibodies against acetylcholine receptors in
      the postsynaptic motor end-plate. Myasthenic crisis (MC) is a complication of MG
      characterized by worsening muscle weakness, resulting in respiratory failure that
      requires intubation and mechanical ventilation. It also includes postsurgical
      patients, in whom exacerbation of muscle weakness from MG causes a delay in
      extubation. MC is a very important, serious, and reversible neurological
      emergency that affects 20-30% of the myasthenic patients, usually within the
      first year of illness and maybe the debut form of the disease. Most patients have
      a predisposing factor that triggers the crisis, generally an infection of the
      respiratory tract. Immunoglobulins, plasma exchange, and steroids are the
      cornerstones of immunotherapy. Today with the modern neurocritical care,
      mortality rate of MC is less than 5%. 

PMID- 24141445
TI  - Professor Abraham Akerman.
AB  - The authors present a historical review of the contribution of Professor Abraham
      Akerman to Brazilian neurology, including the famous sign known as "the
      Alajouanine-Akerman unstable ataxic hand". 

PMID- 24141446
TI  - Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging
      in the investigation of Lambert-Eaton myasthenic syndrome.

PMID- 24141448
TI  - Transport of dynamic biochemical signals in steady flow in a shallow Y-shaped
      microfluidic channel: effect of transverse diffusion and longitudinal dispersion.
AB  - Dynamic biochemical signal control is important in in vitro cell studies. This
      work analyzes the transportation of dynamic biochemical signals in steady and
      mixing flow in a shallow, Y-shaped microfluidic channel. The characteristics of
      transportation of different signals are investigated, and the combined effect of
      transverse diffusion and longitudinal dispersion is studied. A method is
      presented to control the widths of two steady flows in the mixing channel from
      two inlets. The transfer function and the cutoff frequency of the mixing channel
      as a transmission system are presented by analytically solving the governing
      equations for the time-dependent Taylor-Aris dispersion and molecular diffusion.
      The amplitude and phase spectra show that the mixing Y-shaped microfluidic
      channel acts as a low-pass filter due to the longitudinal dispersion. With
      transverse molecular diffusion, the magnitudes of the output dynamic signal are
      reduced compared to those without transverse molecular diffusion. The inverse
      problem of signal transportation for signal control is also solved and analyzed.

PMID- 24141449
TI  - Molecular mechanisms of cellular mechanosensing.
AB  - Mechanical forces direct a host of cellular and tissue processes. Although much
      emphasis has been placed on cell-adhesion complexes as force sensors, the forces
      must nevertheless be transmitted through the cortical cytoskeleton. Yet how the
      actin cortex senses and transmits forces and how cytoskeletal proteins interact
      in response to the forces is poorly understood. Here, by combining molecular and
      mechanical experimental perturbations with theoretical multiscale modelling, we
      decipher cortical mechanosensing from molecular to cellular scales. We show that
      forces are shared between myosin II and different actin crosslinkers, with myosin
      having potentiating or inhibitory effects on certain crosslinkers. Different
      types of cell deformation elicit distinct responses, with myosin and alpha
      actinin responding to dilation, and filamin mainly reacting to shear. Our
      observations show that the accumulation kinetics of each protein may be explained
      by its molecular mechanisms, and that protein accumulation and the cell's
      viscoelastic state can explain cell contraction against mechanical load. 

PMID- 24141450
TI  - Highly sensitive nanoscale spin-torque diode.
AB  - Highly sensitive microwave devices that are operational at room temperature are
      important for high-speed multiplex telecommunications. Quantum devices such as
      superconducting bolometers possess high performance but work only at low
      temperature. On the other hand, semiconductor devices, although enabling high
      speed operation at room temperature, have poor signal-to-noise ratios. In this
      regard, the demonstration of a diode based on spin-torque-induced ferromagnetic
      resonance between nanomagnets represented a promising development, even though
      the rectification output was too small for applications (1.4 mV mW(-1)). Here we
      show that by applying d.c. bias currents to nanomagnets while precisely
      controlling their magnetization-potential profiles, a much greater radiofrequency
      detection sensitivity of 12,000 mV mW(-1) is achievable at room temperature,
      exceeding that of semiconductor diode detectors (3,800 mV mW(-1)). Theoretical
      analysis reveals essential roles for nonlinear ferromagnetic resonance, which
      enhances the signal-to-noise ratio even at room temperature as the size of the
      magnets decreases.

PMID- 24141452
TI  - Three-dimensional ordered macroporous MnO2/carbon nanocomposites as high
      performance electrodes for asymmetric supercapacitors.
AB  - MnO2/carbon composites with ultrathin MnO2 nanofibers (diameter of 5-10 nm)
      uniformly deposited on three dimensional ordered macroporous (3DOM) carbon
      frameworks were fabricated via a self-limiting redox process. The MnO2 nanofibers
      provide a large surface area for charge storage, whereas the 3DOM carbon serves
      as a desirable supporting material providing rapid ion and electron transport
      through the composite electrodes. Cyclic voltammetry, galvanostatic charge
      discharge and electrochemical impedance spectroscopy (EIS) were used to
      characterize the capacitive performance of these composites. Optimization of the
      composition results in a composite with 57 wt% MnO2 content, which gives both a
      high specific capacitance (234 F g(-1) at a discharge current of 0.1 A g(-1)) and
      good rate capability (52% retention of the capacitance at 5 A g(-1)). An
      asymmetric supercapacitor was fabricated by assembling the optimized MnO2/carbon
      composite as the positive electrode and 3DOM carbon as the negative electrode.
      The asymmetric supercapacitor exhibits superior electrochemical performances,
      which can be reversibly charged and discharged at a maximum cell voltage of 2.0 V
      in 1.0 M Na2SO4 aqueous electrolyte, delivering both high energy density (30.2 W
      h kg(-1)) and power density (14.5 kW kg(-1)). Additionally, the asymmetric
      supercapacitor exhibits an excellent cycle life, with 95% capacitance retained
      after 1000 cycles. 

PMID- 24141451
TI  - Biophysical regulation of epigenetic state and cell reprogramming.
AB  - Biochemical factors can help reprogram somatic cells into pluripotent stem cells,
      yet the role of biophysical factors during reprogramming is unknown. Here, we
      show that biophysical cues, in the form of parallel microgrooves on the surface
      of cell-adhesive substrates, can replace the effects of small-molecule epigenetic
      modifiers and significantly improve reprogramming efficiency. The mechanism
      relies on the mechanomodulation of the cells' epigenetic state. Specifically,
      decreased histone deacetylase activity and upregulation of the expression of WD
      repeat domain 5 (WDR5)--a subunit of H3 methyltranferase--by microgrooved
      surfaces lead to increased histone H3 acetylation and methylation. We also show
      that microtopography promotes a mesenchymal-to-epithelial transition in adult
      fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects
      similar to those produced by microgrooves, suggesting that changes in cell
      morphology may be responsible for modulation of the epigenetic state. These
      findings have important implications in cell biology and in the optimization of
      biomaterials for cell-engineering applications.

PMID- 24141453
TI  - Aminoglycosides: how should we use them in the 21st century?
AB  - PURPOSE OF REVIEW: Aminoglycoside antibiotics (AGAs) have proved an invaluable
      part of our antimicrobial armamentarium since their introduction into practice
      over 60 years ago. This review summarizes recent developments, defining their
      role in the context of the current global epidemic of antibiotic resistance,
      raising awareness of their toxicity profile, and highlighting current data on
      their utility as synergistic agents. RECENT FINDINGS: Clinicians are facing an
      unprecedented threat from antibiotic resistance, resulting in an increased
      reliance on the addition of an AGA to provide adequate empirical cover in cases
      of severe sepsis. Concurrently, an increased awareness of the potential for
      severe disability, particularly from vestibular toxicity, has restrained directed
      therapy of AGAs to situations in which there are no appropriate alternatives.
      Their role as synergistic agents in the treatment of enterococcal endocarditis is
      currently under reevaluation, and new data have emerged on combination therapy
      for Pseudomonas aeruginosa bacteremia. AGAs are themselves coming under
      increasing threat from resistance, predominately from aminoglycoside modifying
      enzymes (mediating selective resistance) and 16S rRNA methyltransferases
      (conferring class-wide resistance). New agents and the development of alternate
      ways to circumvent resistance are likely to have important roles in future
      clinical care. SUMMARY: Aminoglycosides retain an invaluable but well defined
      role, and will remain important agents into the foreseeable future.

PMID- 24141455
TI  - Systematic review of clinical trials of aripiprazole for treating attention
      deficit hyperactivity disorder.
AB  - This systematic review assesses the effectiveness and safety of aripiprazole for
      treating attention deficit hyperactivity disorder (ADHD). The databases of
      PubMed/MEDLINE and Google Scholar were searched. All the controlled and non
      controlled trials of aripiprazole for the treatment of ADHD were included. The
      latest search was conducted in March 2013. The quality of studies was assessed,
      and the efficacy and adverse effects were evaluated. Out of 34 relevant retrieved
      titles, only 2 articles reported randomized double blind controlled clinical
      trials. None of the controlled trials reported that aripiprazole was effective.
      However, a very high rate of adverse effects such as weight gain, sedation, and
      headache were reported. No well-controlled clinical trial was found. In contrary
      to non-controlled studies, the findings of controlled trials do not support the
      effectiveness of aripiprazole for treating ADHD. In addition, the high rate of
      adverse effects suggests that more controlled trials require to be conducted to
      reach a conclusion. 

PMID- 24141454
TI  - A high-throughput three-dimensional cell migration assay for toxicity screening
      with mobile device-based macroscopic image analysis.
AB  - There is a growing demand for in vitro assays for toxicity screening in three
      dimensional (3D) environments. In this study, 3D cell culture using magnetic
      levitation was used to create an assay in which cells were patterned into 3D
      rings that close over time. The rate of closure was determined from time-lapse
      images taken with a mobile device and related to drug concentration. Rings of
      human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs)
      were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure
      correlated with the viability and migration of cells in two dimensions (2D).
      Images taken using a mobile device were similar in analysis to images taken with
      a microscope. Ring closure may serve as a promising label-free and quantitative
      assay for high-throughput in vivo toxicity in 3D cultures. 

PMID- 24141456
TI  - Human memory retention and recall processes. A review of EEG and fMRI studies.
AB  - Human memory is an important concept in cognitive psychology and neuroscience.
      Our brain is actively engaged in functions of learning and memorization.
      Generally, human memory has been classified into 2 groups: short-term/working
      memory, and long-term memory. Using different memory paradigms and brain mapping
      techniques, psychologists and neuroscientists have identified 3 memory processes:
      encoding, retention, and recall. These processes have been studied using EEG and
      functional MRI (fMRI) in cognitive and neuroscience research. This study reviews
      previous research reported for human memory processes, particularly brain
      behavior in memory retention and recall processes with the use of EEG and fMRI.
      We discuss issues and challenges related to memory research with EEG and fMRI
      techniques. 

PMID- 24141457
TI  - Parents' knowledge and attitudes toward children with epilepsy.
AB  - OBJECTIVE: To study parents' knowledge and attitude towards children with
      epilepsy, and to identify contributing factors to negative attitudes. METHODS: A
      prospective cross-sectional study including consecutive parents attending the
      pediatric neurology clinics of King Abdulaziz University Hospital, Jeddah, Saudi
      Arabia from February to August 2012. A structured 40-item questionnaire was
      designed to examine their demographics, knowledge, and attitudes. RESULTS: A
      total of 117 parents were interviewed, 57% were mothers. The ages of their
      epileptic children ranged from 1-16 years (median 6.6), mostly boys (65%).
      Although most parents (70%) felt informed and recognized various treatment
      modalities, many believed that epilepsy is a mental disorder (48%), correlates
      with evil (44%), or affects the child's intelligence (38%). Up to 53% admitted to
      treating their child differently and avoiding upsetting or punishing him/her.
      This behavior was less likely if they achieved college education (p=0.01). Some
      parents (29%) admitted to using non-medical treatments, usually traditional or
      religious practices. Those parents were more likely to believe that epilepsy is a
      mental disease (p=0.002), or correlates with evil (p=0.015). CONCLUSION: The
      level of knowledge among parents of epileptic children needs improvement. Many
      have significant misconceptions, negative attitudes, and poor parenting
      practices. Increased awareness and educational programs are needed to improve the
      quality of life of these families.

PMID- 24141458
TI  - Effectiveness of adjuvant temozolomide treatment in patients with glioblastoma.
AB  - OBJECTIVE: To examine whether adjuvant temozolomide treatment improved
      glioblastoma patients' survival in a large Canadian cohort. METHODS: We
      retrospectively studied 364 glioblastoma patients who received different
      modalities of treatment in 2 Canadian tertiary care centers in Edmonton and
      Halifax, Canada, between January 2000 and December 2006. The primary outcome was
      survival following the treatment protocol. RESULTS: The following variables were
      associated with an increased risk of death: The hazard risk (HR) of on-gross
      total resection was 0.50 (95% confidence interval [CI]: 0.39-0.64). The HR for
      the surgery-only group was 5.2 (95% CI: 3.85-7.06). The standard treatment group
      (surgery, radiation therapy [RT], and temozolomide) had an HR of 0.52 (95% CI:
      0.37-0.74). The HR for patients who presented with seizure or whose presentation
      included seizures was 0.88 (95% CI: 0.55-0.89). Patient entry into trials had an
      HR of 0.74 (95% CI: 0.57-0.96). Finally, the HR for age was 1.02 (95% CI: 1.01
      1.03) for every extra year. CONCLUSION: Concomitant temozolomide with RT and
      surgery was associated with longer survival compared with RT with surgery alone.
      We also found that younger age, surgical resection, seizure presence, and entry
      into trials are important prognostic factors for longer survival.

PMID- 24141460
TI  - Leukemia inhibitory factor promotes nestin-positive cells, and increases gp130
      levels in the Parkinson disease mouse model of 6-hydroxydopamine.
AB  - OBJECTIVE: To investigate the roles of leukemia inhibitory factor (LIF) in a 6
      hydroxydopamine (6-OHDA) mouse model of Parkinson disease (PD), and explore how
      the LIF improves PD symptoms. METHODS: This study was performed in Tianjin
      Medical University, Tianjin, China, between April 2008 and January 2010. Seventy
      two mice were allocated into a control group (CON), sham operation group (SHA),
      physiological saline (NS) treatment group (PD), and LIF treatment group (LIF),
      n=18 for each group. The 6-OHDA was injected into the mice's left mid-striatum to
      build a 6-OHDA model of PD. The LIF or NS was slowly released into the CSF
      through the ALZET osmotic pump catheters duct, in the LIF or NS treated groups.
      The whole treatment lasted 3 weeks, and the motor functions of the mice were
      assessed on the seventh, fourteenth, and twenty-first day during the treatment.
      The nestin-positive cells in the mice were counted by immunofluorescence assays,
      and the level of gp130 was detected with western blot analysis. RESULTS: After
      CSF infusion in the LIF-treated group, we observed an increased number of nestin
      positive cells in the mice's brains. The expression of a major component of the
      LIF receptor complex, gp130, was also increased. In the fourteenth and twenty
      first day time periods; LIF treatment continuously improved the motor functions
      of the mouse model of PD. CONCLUSION: These results suggest the potential of LIF
      administration as a therapeutic method for PD.

PMID- 24141459
TI  - Lithium ameliorates open-field and elevated plus maze behaviors, and brain
      phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model
      mice.
AB  - OBJECTIVE: To investigate whether lithium modifies open-field and elevated plus
      maze behavior, and brain phospho-glycogen synthase kinase 3 (P-GSK3beta)
      expression in Fmr1 knockout mice. METHODS: One hundred and eighty FVB mice,
      including knockout and wild type, with an age of 30 days were used. An open-field
      and elevated plus maze was utilized to test behavior, while western blot was used
      to measure the P-GSK3beta expression. Six groups were formed: control (saline),
      lithium chloride 30, 60, 90, 120, and 200 mg/kg. The experiments were carried out
      in the Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical
      University, Guangzhou, China between January and June 2012. RESULTS: Lithium
      significantly decreased total distance, crossing, central area time, and center
      entry in the open-field test (p<0.05), and significantly reduced open-arm
      tracking, open-arm entry, and open-arm time in the elevated plus maze (p<0.05) in
      knockout mice. In wild type mice, significant changes were observed in both
      behavior tests in some treatment groups. Lithium ameliorated P-GSK3beta
      expression in the hippocampus of all the treatment groups in knockout mice
      (p<0.05). However, lithium did not modify either GSK3beta expression in tissues
      of knockout mice, or P-GSK3beta or GSK3beta expression in tissues of wild type
      mice. CONCLUSION: Lithium ameliorated open-field and elevated plus maze behaviors
      of Fmr1 knockout mice. This effect may be related to its enhancement of P
      GSK3beta expression. Our findings suggest that lithium might have a therapeutic
      effect in fragile X syndrome.

PMID- 24141461
TI  - Posterior fossa teratoma.
AB  - Germ cell tumors comprise approximately 2-5% of all childhood brain tumors. They
      arise predominantly in the pineal and suprasellar region, but may occur
      throughout the brain. Teratomas are generally divided into gonadal and
      extragonadal types. A posterior fossa teratoma is a rare occurrence. The focus of
      this discussion is a 5-year-old boy with posterior fossa teratoma who recovered
      completely after medical and surgical intervention. We also present his
      interesting imaging and pathological findings. 

PMID- 24141462
TI  - Spinal cord injuries due to close combat weapons.
AB  - A 17-year-old patient was aggressively attacked and stabbed in the dorsal region
      of his back by a knife. He was admitted to the emergency room of the Hammoud
      Hospital University Medical Center, Saida, Lebanon lying in the prone position.
      The neurological examination revealed that the stabbing object was fixed at the
      dorsal spine level at the T-7 level, where it was inserted inside the vertebral
      body. Luckily, the blade of the knife was parallel to the nervous tracts of the
      spinal cord; thus, he showed no neurological deficits. This case provides an
      overview of how neurosurgical principles can be applied to trauma patients with
      spine injuries due to close combat weapons. 

PMID- 24141463
TI  - Reversible Parkinsonism caused by deep cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) is an uncommon but serious disorder with
      highly variable clinical presentation. Over the past decade, more cases of CVST
      have been diagnosed more frequently and at an early stage of the disease process.
      This is mainly attributed to increased awareness by neurologists and the
      availability of sensitive non-invasive neuro-imaging techniques. Cerebral venous
      sinus thrombosis often affects children, adolescents, and young adults with
      female preponderance. We report a case of Parkinsonism secondary to deep CVST
      (DCVST), which recovered completely following treatment. Recognition of DCVST as
      a cause for Parkinsonism is of paramount importance due to its reversibility and
      favorable outcome when appropriately managed. 

PMID- 24141464
TI  - Decompressive laparotomy for treatment of refractory intracranial hypertension,
      thinking out of the box.

PMID- 24141465
TI  - Long-term follow-up study of patients with spinal cord injury.

PMID- 24141466
TI  - Neonatal dexamethasone exposure in rats resulted in hippocampal learning and
      memory defects with decreased convulsion threshold later in adult life.

PMID- 24141467
TI  - Volume estimation of the rabbit thalamus. Stereological microanatomical study.

PMID- 24141468
TI  - Pathogenesis of cerebral hydatid disease.

PMID- 24141469
TI  - Evolution of epileptic encephalopathy in an infant with non-accidental head
      injury.

PMID- 24141470
TI  - Bronchial asthma control after argon plasma coagulation turbinectomy in patients
      with chronic rhinitis.
AB  - Bronchial asthma is frequently accompanied by chronic rhinitis. It has been
      observed that effective treatment of rhinitis may reduce asthma symptoms. The aim
      of the study was the evaluation of the control of bronchial asthma symptoms in
      patients with chronic rhinitis after argon plasma coagulation turbinectomy
      (APCt). The effect of APCt was assessed in 47 adults with drug-resistant chronic
      rhinitis and bronchial asthma 3-month post-procedure. Changes of asthma symptoms
      were scored using Asthma Control Test (ACT). Subjective improvement of nasal
      congestion 3 months after APCt was observed in 87% and of rhinorrhoea in 75%
      patients. Rhinomanometry showed 219 +/- 19 cm3/s increase of flow and 0.75 +/-
      0.06 Pa/cm3/s reduction of resistance. The prevalence of patients with
      insufficient bronchial asthma control decreased from 79 to 4%. The decrease was
      associated with diminished frequency of eosinophils >20% in nasal cytology from
      83% pre-procedure to 28% in the follow-up. The percentage of eosinophils >20% in
      cytology before APCt increased the chance for asthma control improvement by 22.8
      times. Reduction in symptoms of drug-resistant rhinitis after APCt is followed by
      significant improvement of asthma control. The most beneficial therapeutic
      effects of APCt are noted in patients with a high rate of eosinophils in nasal
      cytology.

PMID- 24141471
TI  - Sudden hearing loss associated with methylphenidate therapy.
AB  - An 8-year-old child diagnosed with attention deficit/hyperactivity disorder
      presented to our Department of Otolaryngology 4 days after suffering hearing
      loss, loss of balance, tinnitus, and fullness sensation of the left ear. Her
      symptoms occured with the first dose of methylphenidate. The medical history and
      physical examination revealed no other diseases associated with sudden hearing
      loss. The audiogram revealed a total hearing loss on the left ear. Stapedial
      reflexes, distortion product and transient-evoked otoacoustic emissions were
      absent in left ear. The absence of clinical, laboratory and radiological evidence
      of a possible cause for complaints, an association between methylphenidate and
      sudden hearing loss was suggested. The patient received a standard course of oral
      corticosteroid and hyperbaric oxygen therapy. Weekly otological and audiological
      examinations were performed. Conservative and medical treatments offered no
      relief from hearing loss. Sudden hearing loss is a serious and irreversible
      adverse effect of methylphenidate. Therefore, the risk of hearing loss should be
      taken into consideration when initiating methylphenidate therapy.

PMID- 24141472
TI  - The influence of pharyngeal and esophageal pressure measurements on the
      parameters of polysomnography.
AB  - Sleep-disordered breathing (SDB) is highly prevalent and accompanied by a
      considerable reduction in quality of life and an increase in cardiovascular
      morbidity and mortality. To diagnose SDB and to assess the localization of an
      airway obstruction, multichannel pressure measurements in the pharynx and
      esophagus have been used but are still under debate. Specifically, these devices
      are often labeled to be uncomfortable for patients and to influence the
      parameters of sleep recordings. The aims of the current study were to determine
      the tolerability of multilevel pressure measurement and to assess their impact on
      the parameters of polysomnography (PSG). Patients who were referred for two
      nights of standard PSG for diagnostic purposes were included. The device for
      multilevel pressure recordings was applied in addition to PSG on one of the two
      nights according to a randomization protocol. Tolerability of the device was
      assessed and the most relevant outcome measures of PSG were compared between the
      nights with and without the pressure sensor. All polysomnographic data were
      analyzed by the same trained observer who was blinded to the presence of the
      pressure catheter. Fifty-one patients were included in the trial. Ten of the
      patients tolerated insertion of the pressure catheter but complained about
      persisting discomfort during the night, requiring removal of the device. Forty
      one patients tolerated the multilevel pressure transducer, which is equivalent to
      a tolerability of 80%. The results of the sleep parameters are based on the data
      of 31 patients. The pressure device minimally influenced the outcome data of the
      PSG. None of the recorded differences however were clinically relevant or
      statistically significant. Pressure measurements with devices of small diameter
      (~2 mm) are well accepted by patients and have a tolerability of at least 80%.
      The impact of multilevel pressure recordings on objective sleep parameters is
      negligible. The study strongly supports the use of multilevel pressure recordings
      and disproves the most relevant objections against their use.

PMID- 24141473
TI  - Laparoscopic repair of primary and incisional ventral hernias: the differences
      must be acknowledged: a prospective cohort analysis of 1,088 consecutive
      patients.
AB  - BACKGROUND: Interpretation of the outcome after laparoscopic repair (LR) of
      ventral hernias presented in the literature often is based on pooled data of
      primary ventral hernias (PVH) and incisional ventral hernias (IVH). This
      prospective cohort study was performed to investigate whether this pooling of
      data is justified. METHODS: The data of 1,088 consecutive patients who underwent
      LR of PVH or IVH were prospectively collected and reviewed for baseline
      characteristics, operative findings, and postoperative complications classified
      as Clavien grade 3 or higher. RESULTS: The PVH group consisted of 662 patients,
      and the IVH group comprised 426 patients. The mean Association of American
      Anesthesiologists classification was higher in IVH group (1.92 vs 1.68; P <=
      0.001), as was rate of conversion to open surgery (7 vs 0.5 %; P < 0.001). The
      IVH group required more adhesiolysis (76 vs 0.9 %; P < 0.001), a longer procedure
      (73 vs 42 min; P < 0.001), and a longer hospital stay (4.53 vs 2.43 days; P <
      0.001). The recurrence rate was higher in the IVH group (5.81 vs 1.37 %; P <
      0.001), as was total complication rate (18.69 vs 4.55 %; P < 0.001). CONCLUSIONS:
      This study showed significant differences in baseline characteristics and
      operative findings between patients undergoing PVH repair and those undergoing
      IVH repair. Continued pooling of data on LR of IVH and PVH combined, commonly
      found in the current literature, seems incorrect.

PMID- 24141474
TI  - Routine cholangiography during rigid-hybrid transvaginal natural orifice
      transluminal endoscopic cholecystectomy.
AB  - BACKGROUND: Transvaginal rigid-hybrid transluminal endoscopic cholecystectomy
      (tvCCE) has become a routine procedure in some laparoscopic departments in recent
      years. Although intraoperative cholangiography is an important adjunct to
      cholecystectomy, its feasibility and safety in tvCCE have not been demonstrated
      to date. METHODS: Patients undergoing tvCCE between April and October 2012 were
      included in this study. An intraoperative cholangiogram was obtained routinely
      for all the patients. Patient characteristics, operation data, feasibility, and
      duration of the cholangiography as well as the postoperative course were recorded
      prospectively. RESULTS: For 32 (97 %) of the 33 patients enrolled in this study,
      intraoperative cholangiography could be performed successfully. The median
      duration of cholangiography was 6 min (interquartile range, 4-7 min). Common bile
      duct stones were detected in three patients (10 %). Laparoscopic bile duct
      revision with the aid of one additional port was successful in two of these
      patients. One patient needed postoperative endoscopic retrograde
      cholangiopancreatography due to the impossibility of extracting an impacted
      prepapillary concrement. One operation was converted to a four-port laparoscopic
      cholecystectomy. One additional port was used in 11 patients (33 %) and two
      additional ports in three patients (9 %). Three intraoperative minor
      complications (9 %) and one postoperative minor complication (3 %) occurred.
      CONCLUSIONS: Intraoperative cholangiography during tvCCE is feasible, safe, and
      easy to perform. The need for intraoperative cholangiography no longer represents
      a contraindication for tvCCE.

PMID- 24141476
TI  - Translation gone awry: differences between commonsense and science.
AB  - A general assumption is that science is just organised commonsense. It is noted
      that translation involves a two-way pathway between basic laboratory science and
      patient care, and that some scientific findings have implications for prevention
      rather than treatment. A succinct critique follows on the key features that
      differentiate science and commonsense. The main part of the paper discusses six
      rather different examples of translation that went awry because people treated
      science and commonsense as equivalent. Examples based on empirical evidence of
      translation going awry include (i) the claim that only early intervention can
      bring lasting benefits; (ii) the claim that the main policy goal for children
      should be the elimination of all stresses; (iii) the claim that exposure in utero
      to maternal smoking causes ADHD and conduct disturbance; (iv) the claim that tax
      benefits should be used to encourage couples to marry; (v) the effects of
      profound institutional deprivation are similar to those of any adversity; and
      (vi) environmental effects are largely independent of genetic influences. Much of
      science is 'unnatural' in the sense that technical tools (such as imaging or DNA)
      are employed, or because animal models are used, or because unusual comparisons
      are made. Science cannot be based solely on an inductive process; rather, there
      must be some form of experiment and the testing of two or more alternative
      explanations. Translation needs to be based on top quality science and an
      appreciation that even the best science needs to take account of multiple
      strategies and multiple evaluations. 

PMID- 24141477
TI  - Flexible omnidirectional carbon dioxide laser as an effective tool for resection
      of brainstem, supratentorial, and intramedullary cavernous malformations.
AB  - BACKGROUND: Lasers have a long history in neurosurgery, yet bulky designs and
      difficult ergonomics limit their use. With its ease of manipulation and multiple
      applications, the OmniGuide CO2 laser has reintroduced laser technology to the
      microsurgical resection of brain and spine lesions. This laser, delivered through
      a hollow-core fiber lined with a unidirectional mirror, minimizes energy loss and
      allows precise targeting. OBJECTIVE: To analyze resections performed by the
      senior author from April 2009 to March 2013 of 58 cavernous malformations (CMs)
      in the brain and spine with the use of the OmniGuide CO2 laser, to reflect on
      lessons learned from laser use in eloquent areas, and to share data on
      comparisons of laser power calibration and histopathology. METHODS: Data were
      collected from electronic medical records, radiology reports, operative room
      records, OmniGuide CO2 laser case logs, and pathology records. RESULTS: Of 58
      CMs, approximately 50% were in the brainstem (30) and the rest were in
      supratentorial (26) and intramedullary spinal locations (2). Fifty-seven, ranging
      from 5 to 45 mm, were resected, with a subtotal resection in 1. Laser power
      ranged from 2 to 10 W. Pathology specimens showed minimal thermal damage compared
      with traditionally resected specimens with bipolar coagulation. CONCLUSION: The
      OmniGuide CO2 laser is safe and has excellent precision for the resection of
      supratentorial, brainstem, and spinal intramedullary CMs. No laser-associated
      complications occurred, and very low energy was used to dissect malformations
      from their surrounding hemosiderin-stained parenchymas. The authors recommend its
      use for deep-seated and critically located CMs, along with traditional tools.

PMID- 24141478
TI  - Development and initial clinical testing of "OPECT": an innovative device for
      fully intangible control of the intraoperative image-displaying monitor by the
      surgeon.
AB  - BACKGROUND: During surgery, various images as well as other relevant visual
      information are usually shown upon request with the help of operating staff.
      However, the lack of direct control over the display may represent a source of
      stress for surgeons, particularly when fast decision making is needed. OBJECTIVE:
      To present the development and initial clinical testing of an innovative device
      that enables surgeons to have direct intangible control of the intraoperative
      image-displaying monitor with standardized free-hand movements. METHODS: The
      originally developed intangible interface named "OPECT" is based on the
      commercially available gaming controller KINECT (Microsoft) and dedicated action
      recognizing algorithm. The device does not require any sensors or markers fixed
      on the hands. Testing was done during 30 neurosurgical operations. After each
      procedure, surgeons completed the 5-item questionnaire for evaluation of the
      system performance, scaling several parameters from 1 (bad) to 5 (excellent).
      RESULTS: During surgical procedures, OPECT demonstrated high effectiveness and
      simplicity of use, excellent quality of visualized graphics, and precise
      recognition of the individual user profile. In all cases, the surgeons were well
      satisfied with performance of the device. The mean score value of answers to the
      questionnaire was 4.7 +/- 0.2. CONCLUSION: OPECT enables the surgeon to easily
      have intangible control of the intraoperative image monitor by using standardized
      free-hand movements. The system has promising potential to be applied for various
      kinds of distant manipulations with the displaying visual information during
      human activities.

PMID- 24141479
TI  - Surgical anatomy of endoscope-assisted approaches to common aneurysm sites.
AB  - BACKGROUND: The endoscope is being introduced as an adjuvant to improve
      visualization of certain areas in open cranial surgery. OBJECTIVE: To describe
      the endoscopic anatomy of common aneurysm sites and to compare it with the
      microsurgical anatomy. METHODS: Pterional, anterior interhemispheric, and
      subtemporal approaches to the most common aneurysm sites were examined in
      cadaveric heads under the surgical microscope and with the endoscope. RESULTS:
      The endoscopic view, particularly with the angled endoscopes, provides a
      significant improvement compared with the microscopic view, especially for poorly
      visualized sites such as the medial aspect of the supraclinoid carotid artery and
      its branches, the area below the anterior perforated substance and optic tract,
      and the carotid and basilar bifurcations. The endoscope aided in the early
      visualization of perforating branches at each aneurysm site except the middle
      cerebral artery. Small-diameter optics (2.7 mm) provided greater space for
      dissection and less potential for tissue damage in narrow places, whereas the
      larger 4-mm diameter optics provided better visualization and less panoramic
      distortion. The positioning of the endoscope for each aneurysm site is reviewed.
      CONCLUSION: The endoscope provides views that complement or improve the
      microscopic view at each aneurysm site except the middle cerebral artery.
      Endoscopy training and a thorough knowledge of endoscopic vascular anatomy are
      essential to safely introduce endoscopic assistance in vascular surgery.

PMID- 24141481
TI  - Percutaneous transfacial direct embolization of an intraosseous dural
      arteriovenous fistula.
AB  - BACKGROUND AND IMPORTANCE: An intraosseous dural arteriovenous fistula (DAVF) is
      a rare cerebrovascular disease. The fistulous connection occurs within
      intraosseous diploic or transosseous emissary veins causing dilated intraosseous
      vascular pouches. To the authors' knowledge, this report describes the first
      percutaneous transfacial direct embolization of an intraosseous DAVF. CLINICAL
      PRESENTATION: A man in his 50s with blue rubber bleb nevus syndrome presented
      with headaches, imbalance, decreased visual acuity bilaterally, and left eye
      proptosis and chemosis. Imaging demonstrated an extensive intraosseous DAVF with
      dilated intraosseous vascular pouches throughout his cranial base and
      intraorbital venous congestion. He underwent staged endovascular treatment with
      the goal to improve his ocular symptoms. Transarterial and transvenous approaches
      failed to provide adequate access to the intraosseous vascular pouches. A direct,
      percutaneous transfacial approach was used to access the pouches for embolization
      with coils and liquid embolic material. Postoperative angiography demonstrated
      successful embolization of the pouch within the left pterygoid wing, reduced
      opacification of the intraosseous fistula, and elimination of intraorbital venous
      congestion. At 9-month follow-up, the patient's headaches had resolved, and his
      ocular symptomatology had improved. CONCLUSION: Endovascular access to an
      intraosseous DAVF is limited by the size and location of the intraosseous
      vascular pouches. In this case, a direct transfacial approach under image
      guidance facilitated access and embolization, which led to an improvement in the
      patient's symptoms. This technique is a novel approach for DAVF management.

PMID- 24141482
TI  - Failures in temporal lobe epilepsy surgery.

PMID- 24141483
TI  - Is there a contribution of anesthesia to the outcome of the SAMMPRIS trial?

PMID- 24141484
TI  - Groundwater levels time series sensitivity to pluviometry and air temperature: a
      geostatistical approach to Sfax region, Tunisia.
AB  - In this paper, the pattern of groundwater level fluctuations is investigated by
      statistical techniques for 24 monitoring wells located in an unconfined coastal
      aquifer in Sfax (Tunisia) for a time period from 1997 to 2006. Firstly, a
      geostatistical study is performed to characterize the temporal behaviors of data
      sets in terms of variograms and to make predictions about the value of the
      groundwater level at unsampled times. Secondly, multivariate statistical methods,
      i.e., principal component analysis (PCA) and cluster analysis (CA) of time series
      of groundwater levels are used to classify groundwater hydrographs regard to
      identical fluctuation pattern. Three groundwater groups (A, B, and C) were
      identified. In group "A," water level decreases continuously throughout the study
      periods with rapid annual cyclic variation, whereas in group "B," the water level
      contains much less high-frequency variation. The wells of group "C" represents a
      steady and gradual increase of groundwater levels caused by the aquifer
      artificial recharge. Furthermore, a cross-correlation analysis is used to
      investigate the aquifer response to local rainfall and temperature records. The
      result revealed that the temperature is more affecting the variation of the
      groundwater level of group A wells than the rainfall. However, the second and the
      third groups are less affected by rainfall or temperature. 

PMID- 24141485
TI  - Soil erosion and sediment fluxes analysis: a watershed study of the Ni Reservoir,
      Spotsylvania County, VA, USA.
AB  - Anthropogenic forces that alter the physical landscape are known to cause
      significant soil erosion, which has negative impact on surface water bodies, such
      as rivers, lakes/reservoirs, and coastal zones, and thus sediment control has
      become one of the central aspects of catchment management planning. The revised
      universal soil loss equation empirical model, erosion pins, and isotopic sediment
      core analyses were used to evaluate watershed erosion, stream bank erosion, and
      reservoir sediment accumulation rates for Ni Reservoir, in central Virginia. Land
      use and land cover seems to be dominant control in watershed soil erosion, with
      barren land and human-disturbed areas contributing the most sediment, and forest
      and herbaceous areas contributing the least. Results show a 7 % increase in human
      development from 2001 (14 %) to 2009 (21.6 %), corresponding to an increase in
      soil loss of 0.82 Mg ha(-1) year(-1) in the same time period. (210)Pb-based
      sediment accumulation rates at three locations in Ni Reservoir were 1.020, 0.364,
      and 0.543 g cm(-2) year(-1) respectively, indicating that sediment accumulation
      and distribution in the reservoir is influenced by reservoir configuration and
      significant contributions from bedload. All three locations indicate an increase
      in modern sediment accumulation rates. Erosion pin results show variability in
      stream bank erosion with values ranging from 4.7 to 11.3 cm year(-1). These
      results indicate that urban growth and the decline in vegetative cover has
      increased sediment fluxes from the watershed and poses a significant threat to
      the long-term sustainability of the Ni Reservoir as urbanization continues to
      increase. 

PMID- 24141486
TI  - The effects of pipeline construction disturbance on soil properties and
      restoration cycle.
AB  - Disturbance to the physical-chemical properties of soil caused by pipeline
      installation was evaluated using two soil quality indices to identify the scale
      of disturbance and the restoration cycle. The integrated soil quality index (SQI)
      was used to evaluate soil property changes in different pipeline zones (0, 10,
      20, and 50 m from the pipeline) at sites 1 and 2. The soil restoration index
      (SRI) was used to estimate soil recovery from three pipelines with different
      recovery periods (2, 6, and 8 years) at site 3. The results showed that the
      adverse effects of pipeline construction on soil properties mainly occurred in
      the right-of-way (ROW) areas and the impaired zones were in the order trench >
      piling and working areas > 20 and 50 m. The soil restoration cycle may be
      complete within 6 years of construction. At site 3, the SRI in the ROW area of a
      pipeline after 6 years of restoration was close to 100 %, showing full soil
      recovery. However, the SRI in the disturbed areas of a pipeline after 2 years of
      restoration was much lower than that after 6 years of restoration, indicating
      that the soil was still recovering from the disturbance. The topography may
      change the intensity of disturbance in different areas due to the movement
      patterns of heavy machinery and traffic routes. There were local variations in
      the SQI within the pipeline zones, with flat areas suffering greater disturbance
      than hilly areas, indicating that topography should be considered in a pipeline's
      environmental impact assessment. 

PMID- 24141487
TI  - Travel distance to HIV medical care: a geographic analysis of weighted survey
      data from the Medical Monitoring Project in Philadelphia, PA.
AB  - Decisions regarding where patients access HIV care are not well understood. The
      purpose of this analysis was to examine differences in travel distance to care
      among persons receiving care in Philadelphia. A multi-stage sampling design was
      utilized to identify 400 potential participants. 65 % (260/400) agreed to be
      interviewed. Participants were asked questions about medical care, supportive
      services, and geographic location. Distances were calculated between residence
      and care location. 46.3 % travelled more than three miles beyond the nearest
      facility. Uninsured travelled further (6.9 miles, 95 % CI 3.9-9.8) than persons
      with public insurance (3.3 miles, 2.9-3.6). In multivariate analyses, no
      insurance (20/260) was associated with increased distance (p = 0.0005) and
      Hispanic ethnicity was associated with decreased distance (p = 0.0462). Persons
      without insurance travel further but insurance status alone does not explain the
      variability in distance travelled to care. In Philadelphia, Hispanic populations,
      and providers that may be most accessible to them, are spatially contained. 

PMID- 24141488
TI  - Flux modules in metabolic networks.
AB  - The huge number of elementary flux modes in genome-scale metabolic networks makes
      analysis based on elementary flux modes intrinsically difficult. However, it has
      been shown that the elementary flux modes with optimal yield often contain highly
      redundant information. The set of optimal-yield elementary flux modes can be
      compressed using modules. Up to now, this compression was only possible by first
      enumerating the whole set of all optimal-yield elementary flux modes. We present
      a direct method for computing modules of the thermodynamically constrained
      optimal flux space of a metabolic network. This method can be used to decompose
      the set of optimal-yield elementary flux modes in a modular way and to speed up
      their computation. In addition, it provides a new form of coupling information
      that is not obtained by classical flux coupling analysis. We illustrate our
      approach on a set of model organisms. 

PMID- 24141490
TI  - Phosphinate stabilised ZnO and Cu colloidal nanocatalysts for CO2 hydrogenation
      to methanol.
AB  - Colloidal solutions of ZnO-Cu nanoparticles can be used as catalysts for the
      reduction of carbon dioxide with hydrogen. The use of phosphinate ligands for the
      synthesis of the nanoparticles from organometallic precursors improves the
      reductive stability and catalytic activity of the system. 

PMID- 24141489
TI  - Resveratrol enhances ionizing radiation-induced premature senescence in lung
      cancer cells.
AB  - Radiotherapy is used in >50% of patients during the course of cancer treatment
      both as a curative modality and for palliation. However, radioresistance is a
      major obstacle to the success of radiation therapy and contributes significantly
      to tumor recurrence and treatment failure, highlighting the need for the
      development of novel radiosensitizers that can be used to overcome tumor
      radioresistance and, thus, improve the efficacy of radiotherapy. Previous studies
      indicated that resveratrol (RV) may sensitize tumor cells to chemotherapy and
      ionizing radiation (IR). However, the mechanisms by which RV increases the
      radiation sensitivity of cancer cells have not been well characterized. Here, we
      show that RV treatment enhances IR-induced cell killing in non-small cell lung
      cancer (NSCLC) cells through an apoptosis-independent mechanism. Further studies
      revealed that the percentage of senescence-associated beta-galactosidase (SA-beta
      gal)-positive senescent cells was markedly higher in cells treated with IR in
      combination with RV compared with cells treated either with IR or RV alone,
      suggesting that RV treatment enhances IR-induced premature senescence in lung
      cancer cells. Comet assays demonstrate that RV and IR combined treatment causes
      more DNA double-strand breaks (DSBs) than IR or RV treatment alone. DCF-DA
      staining and flow cytometric analyses demonstrate that RV and IR combined
      treatment leads to a significant increase in ROS production in irradiated NSCLC
      cells. Furthermore, our investigation show that inhibition of ROS production by N
      acetyl-cysteine attenuates RV-induced radiosensitization in lung cancer cells.
      Collectively, these results demonstrate that RV-induced radiosensitization is
      associated with significant increase of ROS production, DNA-DSBs and senescence
      induction in irradiated NSCLC cells, suggesting that RV treatment may sensitize
      lung cancer cells to radiotherapy via enhancing IR-induced premature senescence.

PMID- 24141491
TI  - Understanding the mediating effects of relationship quality on technology
      acceptance: an empirical study of e-appointment system.
AB  - This study extends the Technology Acceptance Model (TAM) by incorporating
      relationship quality as a mediator to construct a comprehensive framework for
      understanding the influence on continuance intention in the hospital e
      appointment system. A survey of 334 Taiwanese citizens who were contacted via
      phone or the Internet and Structural Equation Modeling (SEM) is used for path
      analysis and hypothesis tests. The study shows that perceived ease of use (PEOU)
      and perceived usefulness (PU) have significant influence on continuance intention
      through the mediation of relationship quality, consisting of satisfaction and
      trust. The direct impact of relationship quality on continuance intention is also
      significant. The analytical results reveal that the relationship between the
      hospital, patients and e-appointment users can be improved via enhancing the
      continued usage of e-appointment. This paper also proposes a general model to
      synthesize the essence of PEOU, PU, and relationship quality for explaining
      users' continuous intention of e-appointment. 

PMID- 24141492
TI  - An efficient chaotic maps-based authentication and key agreement scheme using
      smartcards for telecare medicine information systems.
AB  - A smartcard-based authentication and key agreement scheme for telecare medicine
      information systems enables patients, doctors, nurses and health visitors to use
      smartcards for secure login to medical information systems. Authorized users can
      then efficiently access remote services provided by the medicine information
      systems through public networks. Guo and Chang recently improved the efficiency
      of a smartcard authentication and key agreement scheme by using chaotic maps.
      Later, Hao et al. reported that the scheme developed by Guo and Chang had two
      weaknesses: inability to provide anonymity and inefficient double secrets.
      Therefore, Hao et al. proposed an authentication scheme for telecare medicine
      information systems that solved these weaknesses and improved performance.
      However, a limitation in both schemes is their violation of the contributory
      property of key agreements. This investigation discusses these weaknesses and
      proposes a new smartcard-based authentication and key agreement scheme that uses
      chaotic maps for telecare medicine information systems. Compared to conventional
      schemes, the proposed scheme provides fewer weaknesses, better security, and more
      efficiency. 

PMID- 24141493
TI  - Quantitative assessment of single-cell RNA-sequencing methods.
AB  - Interest in single-cell whole-transcriptome analysis is growing rapidly,
      especially for profiling rare or heterogeneous populations of cells. We compared
      commercially available single-cell RNA amplification methods with both microliter
      and nanoliter volumes, using sequence from bulk total RNA and multiplexed
      quantitative PCR as benchmarks to systematically evaluate the sensitivity and
      accuracy of various single-cell RNA-seq approaches. We show that single-cell RNA
      seq can be used to perform accurate quantitative transcriptome measurement in
      individual cells with a relatively small number of sequencing reads and that
      sequencing large numbers of single cells can recapitulate bulk transcriptome
      complexity. 

PMID- 24141497
TI  - The history of cerebrospinal fluid analysis in Brazil.
AB  - Analysis on cerebrospinal fluid (CSF) in neurological diagnosis has always been
      considered to be a strong point among the main complementary examinations in
      Brazil. The present paper reviews the main events in the history of CSF in the
      neurological sciences, with emphasis on the founders of several CSF schools in
      our country from the beginning of the 20th century to the present time. 

PMID- 24141495
TI  - High-throughput fingerprinting of human pluripotent stem cell fate responses and
      lineage bias.
AB  - Populations of cells create local environments that lead to emergent
      heterogeneity. This is particularly evident with human pluripotent stem cells
      (hPSCs): microenvironmental heterogeneity limits hPSC cell fate control. We
      developed a high-throughput platform to screen hPSCs in configurable
      microenvironments in which we optimized colony size, cell density and other
      parameters to achieve rapid and robust cell fate responses to exogenous cues. We
      used this platform to perform single-cell protein expression profiling, revealing
      that Oct4 and Sox2 costaining discriminates pluripotent, neuroectoderm, primitive
      streak and extraembryonic cell fates. We applied this Oct4-Sox2 code to analyze
      dose responses of 27 developmental factors to obtain lineage-specific
      concentration optima and to quantify cell line-specific endogenous signaling
      pathway activation and differentiation bias. We demonstrated that short-term
      responses predict definitive endoderm induction efficiency and can be used to
      rescue differentiation of cell lines reticent to cardiac induction. This platform
      will facilitate high-throughput hPSC-based screening and quantification of
      lineage-induction bias. 

PMID- 24141498
TI  - Invasive meningococcal disease.
AB  - Invasive meningococcal disease (IMD) is a major public health and continues to
      cause substantial mortality and morbidity. Serotype C is the most frequent in
      Brazil. The clinical spectrum of IMD is broad (meningitis, meningococcemia or
      both) and the clinical evolution may be unpredictable. Main features associated
      with mortality are: age higher than 50 years old, seizures, shock, and
      meningococcemia without meningitis. Blood cultures should be obtained
      immediately. Lumbar puncture can be performed without previous computed
      tomography scan (CT) in most cases. Clinical features can be useful to predic
      patients where an abnormal CT scan is likely. Cerebrospinal fluid (CSF) culture
      and Gram stain should always be required. Latex agglutination sensitivity is
      highly variable. Polymerase chain reaction is specially useful when other methods
      are negative or delayed. Usually ceftriaxone should not be delayed while awaiting
      CSF study or CT. Dexamethasone can be used in meningococcal meningitis. Early
      suspicion of IMD and antibiotic in primary care before hospitalization, rapid
      transportation to a hospital, and stabilization in an intensive-care unit has
      substantially reduced the case-fatality rate. Vaccines against serotypes A, C, W
      135, and Y are available while vaccines against serotype B are expected. 

PMID- 24141494
TI  - Metagenomic species profiling using universal phylogenetic marker genes.
AB  - To quantify known and unknown microorganisms at species-level resolution using
      shotgun sequencing data, we developed a method that establishes metagenomic
      operational taxonomic units (mOTUs) based on single-copy phylogenetic marker
      genes. Applied to 252 human fecal samples, the method revealed that on average
      43% of the species abundance and 58% of the richness cannot be captured by
      current reference genome-based methods. An implementation of the method is
      available at http://www.bork.embl.de/software/mOTU/. 

PMID- 24141499
TI  - Iatrogenic meningitis.
AB  - Iatrogenic meningitis can be caused by a number of mechanisms. The recent case
      reports of fungal meningitis after application of epidural methylprednisolone
      caused warning in the medical community. Cases were caused by contaminated lots
      of methylprednisolone from a single compounding pharmacy. Several medications can
      cause meningitis by probable hypersensitivity mechanism. Neurologists should be
      alert to the recent description of the use of lamotrigine and development of
      aseptic meningitis.

PMID- 24141500
TI  - Leprosy neuropathy: clinical presentations.
AB  - Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium
      leprae. The different clinical presentations of the disease are determined by the
      quality of the host immune response. Early detection of leprosy and treatment by
      multidrug therapy are the most important steps in preventing deformity and
      disability. Thus the early recognition of the clinical leprosy presentation is
      essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation)
      are the most frequent. The frequent anesthetic skin lesions are absent in the
      pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is
      common, including the cranial ones. Arthritic presentation is occasionally seen,
      usually misdiagnosed as rheumatoid arthritis. Attention should be given to
      autonomic dysfunctions in leprosy. There are clinical presentations with severe
      neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy
      (LLON) clinical presentation should be considered facing a patient who develop an
      inflammatory neuropathy many years after a previous skin leprosy treatment. 

PMID- 24141501
TI  - Neurological complications in dengue infection: a review for clinical practice.
AB  - Dengue is an important global public health problem. The World Health
      Organization estimates that 2/5 of entire world population are in risk of dengue
      infection. Almost 50 millions cases occur annually, with at least 20 thousand
      deaths. The etiological agent of this acute febrile disease is a single-strand
      positive-sense RNA virus of Flavivirus genus. It is an arboviral disease
      transmitted by Aedes sp. mosquitoes (Aedes aegypti and A. albopictus). Most
      infected individuals present asymptomatic infection, but some may develop
      clinical signs. Therefore, a wide spectrum of illness can be observed, ranging
      from unapparent, mild disease, called dengue fever, to a severe and occasionally
      fatal dengue hemorrhagic fever/dengue shock syndrome. Currently, neurological
      manifestations related to dengue infections are increasingly been observed and
      appears as a challenge for medical practice. In this study the neurological
      complications of dengue infection will be reviewed, focusing a better
      understanding of the disease for the clinical practice. 

PMID- 24141502
TI  - Evolution of bacterial meningitis diagnosis in Sao Paulo State-Brazil and future
      challenges.
AB  - Bacterial meningitis (BM) is a severe disease and still represents a serious
      public health problem with high rates of morbidity and mortality. The most common
      cases of BM around the world, mainly in Brazil, have been caused by Neisseria
      meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b.
      Bacterial culture is the gold-standard technique for BM confirmation, but
      approximately 50% of suspected cases are not culture-confirmed, due to problems
      related to improper transportation and seeding or previous antibiotic treatment.
      Immunological methods present low sensitivity and have possibility of cross
      reactions. Real time PCR (qPCR) is a molecular technique and has been successful
      used for BM diagnosis at Instituto Adolfo Lutz in Sao Paulo State, Brazil, since
      2007. The incorporation of qPCR in the Public Health surveillance routine in our
      state resulted in diminishing 50% of undetermined BM cases. Our efforts are
      focused on qPCR implementation in the BM diagnostic routine throughout Brazil. 

PMID- 24141503
TI  - Cerebrospinal fluid approach on neuro-oncology.
AB  - Central nervous system (CNS) involvement is a major complication of
      haematological and solid tumors with an incidence that ranges from 10% in solid
      malignancies up to 25% in specific leukaemia or lymphoma subtypes. Cerebrospinal
      fluid (CSF) patterns are unspecific. Though CSF cytology has a high specificity
      (up to 95%), its sensitivity is generally less than 50% and no diagnostic gold
      standard marker is available, yet. New technologies such as flow cytometry,
      molecular genetics and newer biomarkers may improve diagnostic sensitivity and
      specificity, leading to the CNS involvement diagnosis, and consequently, to an
      effective prophylaxis and successful treatment.

PMID- 24141504
TI  - Why should we use atraumatic needles in lumbar puncture?
AB  - Diagnostic lumbar puncture is essential to the diagnosis of central nervous
      system infections, subarachnoid haemorrhage and others neurological diseases.
      Myeloradicular involvement or life-threatening adverse events due to the
      procedure are rare, but less severe complications are more frequent. Post-lumbar
      puncture headache is the most common complication, by spinal fluid leakage due to
      delayed closure of a dural defect. Therefore, the development of fine needles,
      with differentiated atraumatic bevel, has contributed to minimize that problem.
      These generically called atraumatic needles cause less deformation of the dura
      mater then the Quincke((r)) ones. So, why don't we use these atraumatic needles?

PMID- 24141505
TI  - Cerebrospinal fluid analysis in the context of CNS demyelinating diseases.
AB  - The central nervous system demyelinating diseases are a group of disorders with
      different etiologies, characterized by inflammatory lesions that are associated
      with loss of myelin and eventually axonal damage. In this group the most studied
      ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute
      disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to
      differentiate between these different syndromes and to define multiple sclerosis,
      helping to assess the probability of Clinical Isolated Syndrome turn into
      multiple sclerosis. 

PMID- 24141506
TI  - Cognitive impairment and major depressive disorder in HIV infection and
      cerebrospinal fluid biomarkers.
AB  - Cognitive impairment and major depressive disorder (MDD) are common HIV-1 central
      nervous system (CNS) complications. Their frequencies in AIDS patients are 36%
      and 45%, respectively. The diagnoses of HIV cognitive impairment are made by
      clinical criteria, no single laboratory test or biomarker establishes the
      diagnosis. Factors of indirect neuronal injury related with the pathophysiology
      of the HIV infection in the CNS, are the factors studied as biomarkers. In the
      present no biomarker is established to the diagnosis of HIV cognitive impairment,
      much still needs to be done. We review in this paper some biomarkers in
      cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive
      impairment. Diagnosing depression in the context of HIV can be challenging, to
      identify a biomarker that could help in the diagnosis would be very important,
      although MDD risks and neurobiology are still poorly understood. 

PMID- 24141507
TI  - Cerebrospinal fluid analysis in infectious diseases of the nervous system: when
      to ask, what to ask, what to expect.
AB  - Cerebrospinal fluid (CSF) analysis very frequently makes the difference to the
      diagnosis, not only in relation to infections but also in other diseases of the
      nervous system such as inflammatory, demyelinating, neoplastic and degenerative
      diseases. The authors review some practical and important features of CSF
      analysis in infectious diseases of the nervous system, with regard to acute
      bacterial meningitis, herpetic meningoencephalitis, neurotuberculosis,
      neurocryptococcosis, neurocysticercosis and neurosyphilis. 

PMID- 24141508
TI  - Progressive multifocal leukoencephalopathy: new concepts.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the CNS caused by reactivation of JC virus (JCV) in a setting of cellular
      immunosuppression. Originally, PML was observed in patients with advanced HIV
      infection, lymphoproliferative disorders and transplant recipients. However, the
      widespread use of HIV antiretroviral drugs and the new selective immunomodulatory
      and immunosuppressive medications, such as Rituximab and Natalizumab, has
      recently modified the epidemiology, clinical presentation and prognosis of PML.
      Herein, we discuss the new concepts on PML, emphasizing the recent modification
      in the epidemiology; the impact of new immunomodulatory treatments in the
      disease, PML-IRIS (Immune reconstitution inflammatory syndrome), new treatment
      strategies and other JCV related CNS diseases.

PMID- 24141509
TI  - Viral encephalitis.
AB  - While systemic viral infections are exceptionally common, symptomatic viral
      infections of the brain parenchyma itself are very rare, but a serious neurologic
      condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases
      per 100.000 inhabitants. Geography is a major determinant of encephalitis caused
      by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge
      to the clinician, since almost 70% of viral encephalitis cases are left without
      an etiologic agent identified. In this review, the most common viral encephalitis
      will be discussed, with focus on ecology, diagnosis, and clinical management. 

PMID- 24141510
TI  - Neurocysticercosis.
AB  - Cysticercosis is one of the most common parasitic diseases of the nervous system
      in humans, and constitutes a major public health problem for most of the
      developing world. The clinical manifestations of neurocysticercosis (NCC) largely
      depend on the the host immune response against the parasite. NCC diagnosis is
      based upon neuroimaging studies (computerized tomography, magnetic resonance
      imaging) and antibody/antigen detection in the serum and the cerebrospinal fluid.
      Anticysticercal therapy has been marked by an intense controversy. Randomized
      controlled trials evaluating the clinical benefit of treatment have yield
      conflicting data with some studies indicating a benefit and others failing to
      show a difference. Prevention strategies must rely on multiple approaches,
      tailoring each to the special features of the particular endemic area. 

PMID- 24141511
TI  - Mansonic neuroschistosomiasis.
AB  - Mansonic neuroschistosomiasis (MN) is not only the most common but also the most
      serious ectopic presentation of the infection by Schistosoma mansoni. Both, brain
      and spinal cord can be independently affected by the infection, but the later is
      more frequently affected. Brain MN by itself is due to the presence of eggs
      and/or adult worms in situ and can be symptomatic or asymptomatic. Unlike the
      brain MN, spinal cord mansonic neuroschistosomiasis is more frequently
      symptomatic. In both forms the intensity, the seriousness and also the clinical
      characteristics of signs and symptoms depend on the amount of eggs in the
      compromised region and on the intensity of the inflammatory reaction surrounding
      the eggs. Cerebrospinal fluid examination and magnetic resonance imaging are
      important diagnostic tools. Both corticosteroids and drugs against S. mansoni are
      used in the treatment. The outcome may largely depend upon the prompt use of
      these drugs. 

PMID- 24141512
TI  - Steroids in neuroinfection.
AB  - The consequences of inflammatory response are primarily responsible for
      morbimortality in bacterial meningitis. Early use of steroids in these cases can
      reduce mortality and hearing loss and improve functional outcome without causing
      significant side effects. The formal recommendation towards pneumoccocal
      meningitis is being extended to other forms of Bacterial Meningitis. The same
      thought can be applied to tuberculous meningitis. In neurocysticercosis and
      neuroschistosomiasis steroids are more useful than parasiticides in most cases.
      Despite the evidence favoring the use of steroids in herpes simplex encephalitis,
      it is not sufficient to definitely support such indication. Among the
      opportunistic infections that affect AIDS patients, neurotoxoplasmosis and
      progressive multifocal leukoencephalopaty are those most often considered for the
      use of steroids; steroids are safe to use, but no definite benefit could be
      demonstrated in both conditions. 

PMID- 24141513
TI  - Paleoparasitology: the origin of human parasites.
AB  - Parasitism is composed by three subsystems: the parasite, the host, and the
      environment. There are no organisms that cannot be parasitized. The relationship
      between a parasite and its host species most of the time do not result in damage
      or disease to the host. However, in a parasitic disease the presence of a given
      parasite is always necessary, at least in a given moment of the infection. Some
      parasite species that infect humans were inherited from pre-hominids, and were
      shared with other phylogenetically close host species, but other parasite species
      were acquired from the environment as humans evolved. Human migration spread
      inherited parasites throughout the globe. To recover and trace the origin and
      evolution of infectious diseases, paleoparasitology was created.
      Paleoparasitology is the study of parasites in ancient material, which provided
      new information on the evolution, paleoepidemiology, ecology and phylogenetics of
      infectious diseases. 

PMID- 24141514
TI  - Multiple sclerosis and herpesvirus interaction.
AB  - Multiple sclerosis is the most common autoimmune inflammatory demyelinating
      disease of the central nervous system, and its etiology is believed to have both
      genetic and environmental components. Several viruses have already been
      implicated as triggers and there are several studies that implicate members of
      the Herpesviridae family in the pathogenesis of MS. The most important
      characteristic of these viruses is that they have periods of latency and
      exacerbations within their biological sanctuary, the central nervous system. The
      Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7
      viruses are the members that are most studied as being possible triggers of
      multiple sclerosis. According to evidence in the literature, the herpesvirus
      family is strongly involved in the pathogenesis of this disease, but it is
      unlikely that they are the only component responsible for its development. There
      are probably multiple triggers and more studies are necessary to investigate and
      define these interactions. 

PMID- 24141515
TI  - Prionic diseases.
AB  - Prion diseases are neurodegenerative illnesses due to the accumulation of small
      infectious pathogens containing protein but apparently lacking nucleic acid,
      which have long incubation periods and progress inexorably once clinical symptoms
      appear. Prions are uniquely resistant to a number of normal decontaminating
      procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD) and its
      variants, Gerstmann-Straussler-Scheinker (GSS) syndrome and fatal familial
      insomnia (FFI)] result from accumulation of abnormal isoforms of the prion
      protein in the brains of normal animals on both neuronal and non-neuronal cells.
      The accumulation of this protein or fragments of it in neurons leads to apoptosis
      and cell death. There is a strong link between mutations in the gene encoding the
      normal prion protein in humans (PRNP) - located on the short arm of chromosome 20
      - and forms of prion disease with a familial predisposition (familial CJD, GSS,
      FFI). Clinically a prionopathy should be suspected in any case of a fast
      progressing dementia with ataxia, myoclonus, or in individuals with pathological
      insomnia associated with dysautonomia. Magnetic resonance imaging, identification
      of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic
      studies have been used for in vivo diagnosis circumventing the need of brain
      biopsy. Histopathology, however, remains the only conclusive method to reach a
      confident diagnosis. Unfortunately, despite numerous treatment efforts,
      prionopathies remain short-lasting and fatal diseases. 

PMID- 24141516
TI  - Central nervous system infectious diseases mimicking multiple sclerosis:
      recognizing distinguishable features using MRI.
AB  - The current diagnostic criteria for multiple sclerosis (MS) confirm the relevant
      role of magnetic resonance imaging (MRI), supporting the possibility of
      characterizing the dissemination in space (DIS) and the dissemination in time
      (DIT) in a single scan. To maintain the specificity of these criteria, it is
      necessary to determine whether T2/FLAIR visible lesions and the gadolinium
      enhancement can be attributed to diseases that mimic MS. Several diseases are
      included in the MS differential diagnosis list, including diseases with
      exacerbation, remitting periods and numerous treatable infectious diseases, which
      can mimic the MRI features of MS. We discuss the most relevant imaging features
      in several infectious diseases that resemble MS and examine the primary spatial
      distributions of lesions and the gadolinium enhancement patterns related to MS.
      Recognizing imaging "red flags" can be useful for the proper diagnostic
      evaluation of suspected cases of MS, facilitating the correct differential
      diagnosis by assessing the combined clinical, laboratory and MR imaging
      information. 

PMID- 24141517
TI  - Postvaccinal neurological complications.

PMID- 24141518
TI  - The role of spatiotemporal and spectral cues in segregating short sound events:
      evidence from auditory Ternus display.
AB  - Previous studies using auditory sequences with rapid repetition of tones revealed
      that spatiotemporal cues and spectral cues are important cues used to fuse or
      segregate sound streams. However, the perceptual grouping was partially driven by
      the cognitive processing of the periodicity cues of the long sequence. Here, we
      investigate whether perceptual groupings (spatiotemporal grouping vs. frequency
      grouping) could also be applicable to short auditory sequences, where auditory
      perceptual organization is mainly subserved by lower levels of perceptual
      processing. To find the answer to that question, we conducted two experiments
      using an auditory Ternus display. The display was composed of three speakers (A,
      B and C), with each speaker consecutively emitting one sound consisting of two
      frames (AB and BC). Experiment 1 manipulated both spatial and temporal factors.
      We implemented three 'within-frame intervals' (WFIs, or intervals between A and
      B, and between B and C), seven 'inter-frame intervals' (IFIs, or intervals
      between AB and BC) and two different speaker layouts (inter-distance of speakers:
      near or far). Experiment 2 manipulated the differentiations of frequencies
      between two auditory frames, in addition to the spatiotemporal cues as in
      Experiment 1. Listeners were required to make two alternative forced choices
      (2AFC) to report the perception of a given Ternus display: element motion
      (auditory apparent motion from sound A to B to C) or group motion (auditory
      apparent motion from sound 'AB' to 'BC'). The results indicate that the
      perceptual grouping of short auditory sequences (materialized by the perceptual
      decisions of the auditory Ternus display) was modulated by temporal and spectral
      cues, with the latter contributing more to segregating auditory events. Spatial
      layout plays a less role in perceptual organization. These results could be
      accounted for by the 'peripheral channeling' theory.

PMID- 24141519
TI  - When is radiation therapy in head and neck squamous cell carcinoma not indicated?

PMID- 24141520
TI  - Change of Voice Handicap Index after treatment of benign laryngeal disorders.
AB  - Voice disorders can have major impact on quality of life. Problems caused by
      these disorders can be experienced in different domains. The Voice Handicap Index
      (VHI) is a well-known voice-related quality of life instrument to measure
      physical, emotional and functional complaints. VHI change after treatment in
      seven separate benign laryngeal disorders was studied. In addition, correlation
      between the three domains was examined. VHI forms were completed before and 3
      months after treatment. In a 5-year-period, 143 patients with seven specific
      diagnoses were retrospectively included. VHI improved for six diagnoses polyp (p
      < 0.000), cyst (p = 0.001), unilateral paralysis (p = 0.001), Reinke edema (p =
      0.016), papillomatosis (p = 0.001), nodules (p = 0.002). Sulcus glottidis did not
      change (p = 0.897). Mean VHI after treatment was higher for females (p = 0.021).
      The values of the three domains correlate statistically significant. For each
      diagnosis, the mean VHI after treatment remained higher than in subjects with a
      healthy voice. Because the domains are interdependent, their absolute values
      could not be compared. After treatment, VHI improved in six of the seven
      diagnoses. The scores on the physical, emotional, and functional domain are
      interdependent. Scores of the different domains cannot be compared. 

PMID- 24141522
TI  - Effect of pre-stress on the dynamic tensile behavior of the TMJ disc.
AB  - Previous dynamic analyses of the temporomandibular joint (TMJ) disc have not
      included a true preload, i.e., a step stress or strain beyond the initial tare
      load. However, due to the highly nonlinear stress-strain response of the TMJ
      disc, we hypothesized that the dynamic mechanical properties would greatly depend
      on the preload, which could then, in part, account for the large variation in the
      tensile stiffnesses reported for the TMJ disc in the literature. This study is
      the first to report the dynamic mechanical properties as a function of prestress.
      As hypothesized, the storage modulus (E') of the disc varied by a factor of 25 in
      the mediolateral direction and a factor of 200 in the anteroposterior direction,
      depending on the prestress. Multiple constant strain rate sweeps were extracted
      and superimposed via strain-rate frequency superposition (SRFS), which
      demonstrated that the strain rate amplitude and strain rate were both important
      factors in determining the TMJ disc material properties, which is an effect not
      typically seen with synthetic materials. The presented analysis demonstrated, for
      the first time, the applicability of viscoelastic models, previously applied to
      synthetic polymer materials, to a complex hierarchical biomaterial such as the
      TMJ disc, providing a uniquely comprehensive way to capture the viscoelastic
      response of biological materials. Finally, we emphasize that the use of a
      preload, preferably which falls within the linear region of the stress-strain
      curve, is critical to provide reproducible results for tensile analysis of
      musculoskeletal tissues. Therefore, we recommend that future dynamic mechanical
      analyses of the TMJ disc be performed at a controlled prestress corresponding to
      a strain range of 5-10%.

PMID- 24141521
TI  - Analysis of impact noise induced by hitting of titanium head golf driver.
AB  - The hitting of titanium head golf driver against golf ball creates a short
      duration, high frequency impact noise. We analyzed the spectra of these impact
      noises and evaluated the auditory hazards from exposure to the noises. Noises
      made by 10 titanium head golf drivers with five maximum hits were collected, and
      the spectra of the pure impact sounds were studied using a noise analysis
      program. The noise was measured at 1.7 m (position A) and 3.4 m (position B) from
      the hitting point in front of the hitter and at 3.4 m (position C) behind the
      hitting point. Average time duration was measured and auditory risk units (ARUs)
      at position A were calculated using the Auditory Hazard Assessment Algorithm for
      Humans. The average peak levels at position A were 119.9 dBA at the sound
      pressure level (SPL) peak and 100.0 dBA at the overall octave level. The average
      peak levels (SPL and overall octave level) at position B were 111.6 and 96.5 dBA,
      respectively, and at position C were 111.5 and 96.7 dBA, respectively. The
      average time duration and ARUs measured at position A were 120.6 ms and 194.9
      units, respectively. Although impact noises made by titanium head golf drivers
      showed relatively low ARUs, individuals enjoying golf frequently may be
      susceptible to hearing loss due to the repeated exposure of this intense impact
      noise with short duration and high frequency. Unprotected exposure to impact
      noises should be limited to prevent cochleovestibular disorders.

PMID- 24141523
TI  - Structure of RNA-interacting cyclophilin A-like protein from Piriformospora
      indica that provides salinity-stress tolerance in plants.
AB  - Soil salinity problems are widespread around the globe with increased risk of
      spreading over the years. The fungus Piriformospora indica, identified in Indian
      Thar desert, colonizes the roots of monocotyledon plants and provides resistance
      towards biotic as well as abiotic stress conditions. We have identified a
      cyclophilin A-like protein from P. indica (PiCypA), which shows higher expression
      levels during salinity stress. The transgenic tobacco plants overexpressing
      PiCypA develop osmotic tolerance and exhibit normal growth under osmotic stress
      conditions. The crystal structure and NMR spectroscopy of PiCypA show a canonical
      cyclophilin like fold exhibiting a novel RNA binding activity. The RNA binding
      activity of the protein and identification of the key residues involved in the
      RNA recognition is unique for this class of protein. Here, we demonstrate for the
      first time a direct evidence of countering osmotic stress tolerance in plant by
      genetic modification using a P. indica gene. 

PMID- 24141524
TI  - An infant with hypercalcemia: questions.

PMID- 24141525
TI  - An infant with hypercalcemia: answers.

PMID- 24141527
TI  - Activated carbons derived from coconut shells as high energy density cathode
      material for Li-ion capacitors.
AB  - In this manuscript, a dramatic increase in the energy density of ~ 69 Wh kg-1 and
      an extraordinary cycleability ~ 2000 cycles of the Li-ion hybrid electrochemical
      capacitors (Li-HEC) is achieved by employing tailored activated carbon (AC) of ~
      60% mesoporosity derived from coconut shells (CS). The AC is obtained by both
      physical and chemical hydrothermal carbonization activation process, and compared
      to the commercial AC powders (CAC) in terms of the supercapacitance performance
      in single electrode configuration vs. Li. The Li-HEC is fabricated with
      commercially available Li4Ti5O12 anode and the coconut shell derived AC as
      cathode in non-aqueous medium. The present research provides a new routine for
      the development of high energy density Li-HEC that employs a mesoporous
      carbonaceous electrode derived from bio-mass precursors.

PMID- 24141528
TI  - Motor rehabilitation in stroke and traumatic brain injury: stimulating and
      intense.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      latest neurorehabilitation literature for motor recovery in stroke and traumatic
      brain injury to assist clinical decision making and assessing future research
      directions. RECENT FINDINGS: The emerging approach to motor restoration is now
      multimodal. It engages the traditional multidisciplinary rehabilitation team, but
      incorporates highly structured activity-based therapies, pharmacology, brain
      stimulation and robotics. Clinical trial data support selective serotonin
      reuptake inhibitors and amantadine to assist motor recovery poststroke and
      traumatic brain injury, respectively. Similarly, there is continued support for
      intensity as a key factor in activity-based therapies, across skilled and
      nonskilled interventions. Aerobic training appears to have multiple benefits;
      increasing the capacity to meet the demands of hemiparetic gait improves
      endurance for activities of daily living while promoting cognition and mood. At
      this time, the primary benefit of robotic therapy lies in the delivery of highly
      intense and repetitive motor practice. Both transcranial direct current and
      magnetic stimulation therapies are in early stages, but have promise in motor and
      language restoration. SUMMARY: Advancements in neurorehabilitation have shifted
      treatment away from nonspecific activity regimens and amphetamines. As the body
      of knowledge grows, evidence-based practice using interventions targeted at
      specific subgroups becomes progressively more feasible.

PMID- 24141526
TI  - Histopathological diagnosis of acute and chronic rejection in pediatric kidney
      transplantation.
AB  - ABO-compatible as well as ABO-incompatible kidney transplantation are well
      established in the pediatric population. There are particularities in the
      histopathological evaluation of pediatric kidney transplant biopsies as for
      example the recurrence of certain diseases different from the adult population.
      Furthermore, the challenging transition of pediatric renal transplant recipients
      to adulthood is associated with an increased rate of non-adherence triggered
      rejection episodes. With modern immunosuppressive drugs, T-cell-mediated
      rejection of renal allografts is well controlled. In contrast, antibody-mediated
      rejection (AMR) is increasingly recognized as one of the major reasons for
      allograft loss. However, the 2001 diagnostic Banff criteria for antibody-mediated
      rejection require further refinement, as the morphological spectrum of AMR
      expands while effective therapeutic strategies are lacking. For example,
      endarteritis, which traditionally has been attributed to T-cell-mediated
      rejection, has recently been shown to be part of the AMR spectrum in some cases.
      Many findings in transplant renal biopsies are not specific for a certain disease
      but need consideration of differential diagnoses. To use the term "chronic
      allograft nephropathy" as a diagnostic entity is no longer appropriate.
      Therefore, the precise identification of specific diseases is paramount in the
      assessment of transplant renal biopsies in order to enable tailored therapeutic
      management. 

PMID- 24141529
TI  - Ticks collected from migratory birds, including a new record of Haemaphysalis
      formosensis, on Jeju Island, Korea.
AB  - Migratory birds may disperse parasites across ecological barriers, and recent
      climate change may alter the pattern of ectoparasite dispersal via changed
      patterns of bird migration. In order to document the parasitization of migratory
      birds by Ixodidae ticks on Jeju Island in Korea, we examined 934 migratory birds
      comprising 75 species for ticks from 2010 to 2012. In total, 313 ticks were
      collected from 74 migratory birds across 17 avian species and identified based on
      morphological keys. These ticks represented six species: Haemaphysalis flava, H.
      formosensis, H. longicornis, H. concinna, Ixodes turdus and I. nipponensis. Of
      particular note was the presence of H. formosensis, a species not previously
      reported to have been found in Korea, and H. concinna, which had not been
      previously reported on Jeju Island. The dominant tick species found were H. flava
      (226 ticks, 72.2 %) and I. turdus (54 ticks, 17.3 %), and ground-dwelling
      thrushes such as Pale thrushes (Turdus pallidus; 39 birds, 52.7 %) were the most
      important hosts. Although H. longicornis is the most abundant and prevalent
      terrestrial tick on Jeju Island, the species accounted for only 3.8 % of the
      total ticks collected in this study, suggesting that ticks on migratory birds may
      differ from the local tick fauna and that exotic ticks may be introduced via
      migratory birds. Therefore, long-term programs for tick and tick-borne disease
      surveillance are recommended to understand the role of migratory animals in the
      introduction of exotic species and associated pathogens and in life cycles of
      ticks at different stages in this region. 

PMID- 24141531
TI  - Challenges, alternatives, and paths to sustainability for health information
      exchange efforts.
AB  - Health information exchange (HIE) is a promising approach to improving the cost
      and quality of healthcare. We sought to identify the strengths and weaknesses of
      organizational models to achieve exchange, and what can be done to ensure the
      sustainability and effectiveness of exchange efforts. We interviewed state and
      national health informatics policy experts (n = 17). Data were collected as part
      of an evaluation of the Health Care Efficiency and Affordability Law for New
      Yorkers (HEAL NY) program and included respondents from both the private and
      public sectors. Data were analyzed using a general inductive and comparative
      approach with open coding of themes. Interviewees generally viewed HIE as a
      public or societal good to be valued. However, they identified challenges with
      the regional health information organization (RHIO) model of facilitating
      exchange including: economics, organizational issues, and geography. RHIOs were
      contrasted against alternative methods of exchange such as Direct, enterprise
      HIE, and vendor-mediated exchange. HIE is a difficult undertaking due to
      political and economic reasons. Alternatives to the RHIO model have features that
      may be more attractive to participants, but may be of less public benefit. Using
      states as intermediaries and mandating exchange under public health law may avoid
      the challenges facing exchange efforts. Moving forward, policies will have to
      address the shortcomings of each HIE model to ensure information is effectively
      shared between providers to maximize health benefits.

PMID- 24141532
TI  - Laser-induced, in situ, nanoparticle shell synthesis in polymer matrix
      nanocomposites.
AB  - This work investigates processes involved in the patterning and production of
      structured nanoparticles in polymer matrix nanocomposites using femtosecond laser
      irradiation. An in situ, chemical vapor deposition process was used to synthesize
      silver nanoparticles in the bulk of an optically transparent
      polytetrafluoroethylene-co-hexafluoropropylene polymer matrix. The strong optical
      absorption at the surface plasmon resonance frequency was used to selectively
      irradiate and photothermally heat the material near particles using femtosecond
      laser pulses. Having species for chemical vapor deposition in the near-particle
      environment allows for localized decomposition of the precursor species via
      unimolecular reactions. Decomposition products can subsequently participate in
      the production of a variety of core-shell nanostructures. The overall process is
      demonstrated using femtosecond, photothermal heating of silver nanoparticles to
      decompose tungsten hexacarbonyl in the polymer matrix leading to the formation of
      tungsten oxide shells surrounding the silver. For this system, a 40 nm red shift
      of the surface plasmon resonance was measured. Control of the spatial and
      temporal characteristics of the excitation source allows for synthesis of
      nanocomposites with a high degree of control over the location, composition and
      size of nanoparticles in a polymer matrix resulting in patterned materials with
      continuously variable properties. 

PMID- 24141530
TI  - Fuzzy assessment of health information system users' security awareness.
AB  - Health information systems (HIS) are a specific area of information systems (IS),
      where critical patient data is stored and quality health service is only realized
      with the correct use and efficient dissemination of this data to health workers.
      Therefore, a balance needs to be established between the levels of security and
      flow of information on HIS. Instead of implementing higher levels and further
      mechanisms of control to increase the security of HIS, it is preferable to deal
      with the arguably weakest link on HIS chain with respect to security: HIS users.
      In order to provide solutions and approaches for transforming users to the first
      line of defense in HIS but also to employ capable and appropriate candidates from
      the pool of newly graduated students, it is important to assess and evaluate the
      security awareness levels and characteristics of these existing and future users.
      This study aims to provide a new perspective to understand the phenomenon of
      security awareness of HIS users with the use of fuzzy analysis, and to assess the
      present situation of current and future HIS users of a leading medical and
      educational institution of Turkey, with respect to their security characteristics
      based on four different security scales. The results of the fuzzy analysis, the
      guide on how to implement this fuzzy analysis to any health institution and how
      to read and interpret these results, together with the possible implications of
      these results to the organization are provided. 

PMID- 24141533
TI  - Newly developed techniques in andrology: endoscopy of the vas deference and a new
      imaging technique for in situ localization of vital spermatozoa.
AB  - During the past decade, endourology represents the most advanced technology in
      urology which has provided minimal invasive diagnostic and therapeutic tool for
      patients with urology diseases. However, because of the much smaller lumen of
      genital tract, endoscopic andrology remained a dream for andrologists until the
      first clinical application of vesiculoscopy in laser lithotripsy of seminal
      vesicle stones in 2006. Lately, Dr Trottmann at Ludwig-Maximilians University,
      Germany, for the first time established vasoscopy in the seminal duct using a new
      prototype of a microendoscope and also applied a new imaging technique for in
      situ localization of vital spermatozoa. These newly developed techniques will
      greatly speed up the clinical practice of endoandrology.

PMID- 24141534
TI  - Investigating intratumour heterogeneity by single-cell sequencing.
AB  - Intratumour heterogeneity is a longstanding field of focus for both researchers
      and clinicians. It refers to the diversity amongst cells within the same tumour.
      Two major hypotheses have attempted to explain the existence of intratumour
      heterogeneity: (i) the clonal evolution (CE) theory and (ii) the cancer stem cell
      (CSC) model. CE theory emphasizes the evolutionary biological characteristics of
      the tumour, underscoring the initiation and progression of the disease. In
      contrast, the CSC model focuses on stem cell differentiation into distinct
      functions in order to stabilize the tumour microenvironment. Here we consider
      single-cell sequencing (SCS) as a newly developed technique for application to
      the investigation of intratumour heterogeneity and assess its relevance within
      research and clinical environments. Early detection of rare tumour cells,
      monitoring of circulating tumour cells (CTCs) and control of the occurrence of
      drug resistance are important goals in early diagnosis, prognosis prediction and
      individualized medicine.

PMID- 24141535
TI  - Does the autonomic nervous system contribute to the initiation and progression of
      prostate cancer?
AB  - In the July 12 issue of Science magazine, researchers from the Albert Einstein
      College of Medicine, the Mount Sinai School of Medicine, the Durham VA Medical
      Centre and Duke University published an elegant study demonstrating that the
      sympathetic nervous system, acting through beta2 and beta3-adrenoceptors in the
      prostate, plays an important role in the initiation of prostate cancer, while the
      parasympathetic nervous system plays a role in the dissemination of tumour
      metastases via M1 muscarinic receptors. These findings are significant because
      they indicate that receptors associated with the autonomic nervous system may be
      viable targets for prostate cancer therapy.

PMID- 24141537
TI  - Nanoimaging: Hot electrons go through the barrier.

PMID- 24141536
TI  - Serum resistin levels: a possible correlation with pulmonary vascular involvement
      in patients with systemic sclerosis.
AB  - Our latest studies demonstrated the potential role of adipocytokines, including
      adiponectin, visfatin, retinol binding protein-4, and apelin, in the pathogenesis
      of systemic sclerosis (SSc). Given that resistin is another member of
      adipocytokines with pro-inflammatory and pro-angiogenic properties, we measured
      serum resistin levels by enzyme-linked immunosorbent assay in 52 SSc and 19
      control subjects and evaluated their clinical correlation. Since serum resistin
      levels greatly and inversely correlated with estimated glomerular filtration rate
      in SSc patients with renal dysfunction [r = -0.78, p < 0.05 (n = 9)], we
      evaluated the clinical correlation of serum resistin levels in SSc patients with
      normal renal function (n = 43). Although serum resistin levels were comparable
      between diffuse cutaneous SSc (n = 22), limited cutaneous SSc (n = 21), and
      control subjects (n = 19) [median (25-75 percentiles); 18.7 ng/ml (13.3-48.0),
      23.3 ng/ml (12.9-54.1), and 22.9 ng/ml (9.4-36.7), respectively], the prevalence
      of elevated right ventricular systolic pressure (RVSP) was significantly higher
      in SSc patients with elevated serum resistin levels than in those with normal
      levels [67 % (4/6) vs. 16 % (6/37), p < 0.05], and serum resistin levels were
      significantly increased in SSc patients with elevated RVSP (n = 10) as compared
      to those with normal RVSP (n = 33) [52.1 ng/ml (20.8-117.5) vs. 18.5 ng/ml (12.2
      46.2), p < 0.05]. Thus, serum resistin levels may serve as a useful marker for
      pulmonary vascular involvement in SSc, suggesting a possible contribution of
      resistin to the pathogenesis of pulmonary arterial hypertension associated with
      SSc.

PMID- 24141538
TI  - Hot-electron nanoscopy using adiabatic compression of surface plasmons.
AB  - Surface plasmon polaritons are a central concept in nanoplasmonics and have been
      exploited to develop ultrasensitive chemical detection platforms, as well as
      imaging and spectroscopic techniques at the nanoscale. Surface plasmons can decay
      to form highly energetic (or hot) electrons in a process that is usually thought
      to be parasitic for applications, because it limits the lifetime and propagation
      length of surface plasmons and therefore has an adverse influence on the
      functionality of nanoplasmonic devices. Recently, however, it has been shown that
      hot electrons produced by surface plasmon decay can be harnessed to produce
      useful work in photodetection, catalysis and solar energy conversion.
      Nevertheless, the surface-plasmon-to-hot-electron conversion efficiency has been
      below 1% in all cases. Here we show that adiabatic focusing of surface plasmons
      on a Schottky diode-terminated tapered tip of nanoscale dimensions allows for a
      plasmon-to-hot-electron conversion efficiency of ~30%. We further demonstrate
      that, with such high efficiency, hot electrons can be used for a new nanoscopy
      technique based on an atomic force microscopy set-up. We show that this hot
      electron nanoscopy preserves the chemical sensitivity of the scanned surface and
      has a spatial resolution below 50 nm, with margins for improvement. 

PMID- 24141539
TI  - A general strategy for the DNA-mediated self-assembly of functional nanoparticles
      into heterogeneous systems.
AB  - Nanoparticles coated with DNA molecules can be programmed to self-assemble into
      three-dimensional superlattices. Such superlattices can be made from
      nanoparticles with different functionalities and could potentially exploit the
      synergetic properties of the nanoscale components. However, the approach has so
      far been used primarily with single-component systems. Here, we report a general
      strategy for the creation of heterogeneous nanoparticle superlattices using DNA
      and carboxylic-based conjugation. We show that nanoparticles with all major types
      of functionality--plasmonic (gold), magnetic (Fe2O3), catalytic (palladium) and
      luminescent (CdSe/Te@ZnS and CdSe@ZnS)--can be incorporated into binary systems
      in a rational manner. We also examine the effect of nanoparticle characteristics
      (including size, shape, number of DNA per particle and DNA flexibility) on the
      phase behaviour of the heterosystems, and demonstrate that the assembled
      materials can have novel optical and field-responsive properties.

PMID- 24141541
TI  - Graphene-MoS2 hybrid structures for multifunctional photoresponsive memory
      devices.
AB  - Combining the electronic properties of graphene and molybdenum disulphide (MoS2)
      in hybrid heterostructures offers the possibility to create devices with various
      functionalities. Electronic logic and memory devices have already been
      constructed from graphene-MoS2 hybrids, but they do not make use of the
      photosensitivity of MoS2, which arises from its optical-range bandgap. Here, we
      demonstrate that graphene-on-MoS2 binary heterostructures display remarkable dual
      optoelectronic functionality, including highly sensitive photodetection and gate
      tunable persistent photoconductivity. The responsivity of the hybrids was found
      to be nearly 1 * 10(10) A W(-1) at 130 K and 5 * 10(8) A W(-1) at room
      temperature, making them the most sensitive graphene-based photodetectors. When
      subjected to time-dependent photoillumination, the hybrids could also function as
      a rewritable optoelectronic switch or memory, where the persistent state shows
      almost no relaxation or decay within experimental timescales, indicating near
      perfect charge retention. These effects can be quantitatively explained by gate
      tunable charge exchange between the graphene and MoS2 layers, and may lead to new
      graphene-based optoelectronic devices that are naturally scalable for large-area
      applications at room temperature. 

PMID- 24141540
TI  - Multivalent ligands control stem cell behaviour in vitro and in vivo.
AB  - There is broad interest in designing nanostructured materials that can interact
      with cells and regulate key downstream functions. In particular, materials with
      nanoscale features may enable control over multivalent interactions, which
      involve the simultaneous binding of multiple ligands on one entity to multiple
      receptors on another and are ubiquitous throughout biology. Cellular signal
      transduction of growth factor and morphogen cues (which have critical roles in
      regulating cell function and fate) often begins with such multivalent binding of
      ligands, either secreted or cell-surface-tethered to target cell receptors,
      leading to receptor clustering. Cellular mechanisms that orchestrate ligand
      receptor oligomerization are complex, however, so the capacity to control
      multivalent interactions and thereby modulate key signalling events within living
      systems is currently very limited. Here, we demonstrate the design of potent
      multivalent conjugates that can organize stem cell receptors into nanoscale
      clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of
      ephrin-B2, normally an integral membrane protein ligand, was conjugated to a
      soluble biopolymer to yield multivalent nanoscale conjugates that potently induce
      signalling in neural stem cells and promote their neuronal differentiation both
      in culture and within the brain. Super-resolution microscopy analysis yielded
      insights into the organization of the receptor-ligand clusters at the nanoscale.
      We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance
      human embryonic and induced pluripotent stem cell differentiation into functional
      dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and
      potential nanoscale therapeutics for controlling the behaviour of target stem
      cells in vitro and in vivo. 

PMID- 24141542
TI  - Cancer survivorship care: Implications for primary care advanced practice nurses.
AB  - Cancer survivors are at risk for recurrences, new cancers, and late and long-term
      effects of cancer treatments. Health promotion and management of comorbid
      conditions remain a standard of care for cancer survivors. Nurse practitioners
      should collaborate with oncology specialists using a shared-care model in
      delivering survivorship care.

PMID- 24141543
TI  - Elevated prolactin levels in men.

PMID- 24141544
TI  - Detecting and treating hypoglycemia in patients with diabetes.

PMID- 24141548
TI  - Evidence-based treatment of schistosomiasis in pregnancy.
AB  - Schistosomiasis is a parasitic infection that causes significant morbidity and
      mortality, especially in pregnant women originating from developing countries.
      Prompt diagnosis and treatment can improve pregnancy and infant outcomes.
      Currently, there are no formal guidelines for treatment in this population, which
      makes schistosomiasis in pregnancy a challenge to treat.

PMID- 24141550
TI  - Evaluation of acute abdominal pain.
AB  - Abdominal pain is a common complaint encountered in primary care and in the ED.
      Varying levels of pain dictate the immediacy of the intervention. Time is vital
      when making the decision to initiate therapeutic interventions. A comprehensive
      assessment with physical exam and diagnostic studies is required.

PMID- 24141549
TI  - Hiring a nurse practitioner: What's in it for the physician?
AB  - A solution to the increased demand for primary care providers is to hire a nurse
      practitioner (NP). Hiring an NP in a primary care practice has numerous
      advantages for physicians. This article will discuss those advantages and clarify
      perceived disadvantages to hiring an NP in the primary care setting.

PMID- 24141552
TI  - Gloeocapsopsis AAB1, an extremely desiccation-tolerant cyanobacterium isolated
      from the Atacama Desert.
AB  - The comprehensive study of microorganisms that evolved in the Atacama Desert, the
      driest and oldest on earth, may help to understand the key role of water for
      life. In this context, we previously characterized the microenvironment that
      allows colonization of the underside of quartzes in the Coastal Range of this
      desert by hypolithic microorganisms (Azua-Bustos et al. Microb Ecol 58:568-581,
      2011). Now, we describe the biodiversity composition of these biofilms and the
      isolation from it of a new cyanobacterial strain. Based on morphologic and
      phylogenetic analyses, this isolate (AAB1) was classified as a new member of the
      Gloeocapsopsis genus. Physiological, morphological and molecular responses by
      isolate AAB1 show that this strain is extremely tolerant to desiccation. Our
      results also indicate that the isolate biosynthesizes sucrose and trehalose in
      response to this stressful condition. We identified two candidate genes involved
      in sucrose synthesis, namely sucrose 6-phosphate synthase and sucrose 6-phosphate
      phosphatase. Thus, the Gloeocapsopsis isolate AAB1 may represent a suitable model
      for understanding tolerance to low water availability. 

PMID- 24141553
TI  - Assessing the diversity of the virulence potential of Escherichia coli isolated
      from bacteremia in Sao Paulo, Brazil.
AB  - Most of the knowledge of the virulence determinants of extraintestinal pathogenic
      Escherichia coli (ExPEC) comes from studies with human strains causing urinary
      tract infections and neonatal meningitis and animal strains causing avian
      colibacillosis. In this research, we analyzed the phylogenetic background, the
      presence of 20 ExPEC virulence factors, and the intrinsic virulence potential of
      74 E. coli strains isolated in Sao Paulo, Brazil, from 74 hospitalized patients
      (43 males and 31 females) with unknown-source bacteremia. Unlike other places in
      the world, the bacteremic strains originated equally from phylogroups B2 (35%)
      and D (30%). A great variability in the profiles of virulence factors was noted
      in this survey. Nevertheless, 61% of the strains were classified as ExPEC,
      meaning that they possessed intrinsic virulent potential. Accordingly, these
      strains presented high virulence factor scores (average of 8.7), and were
      positively associated with 12 of 17 virulence factors detected. On the contrary,
      the non-ExPEC strains, isolated from 39% of the patients, presented a generally
      low virulence capacity (medium virulence factor score of 3.1), and were
      positively associated with only the colicin cvaC gene. These results show the
      importance of discriminating E. coli isolates that possess characteristics of
      true pathogens from those that may be merely opportunistic in order to better
      understand the virulence mechanisms involved in extraintestinal E. coli
      infections. Such knowledge is essential for epidemiological purposes as well as
      for development of control measures aimed to minimize the incidence of these life
      threatening and costly infections.

PMID- 24141554
TI  - Influence of the dopaminergic system, CREB, and transcription factor-kappaB on
      cocaine neurotoxicity.
AB  - Cocaine is a widely used drug and its abuse is associated with physical,
      psychiatric and social problems. Abnormalities in newborns have been demonstrated
      to be due to the toxic effects of cocaine during fetal development. The mechanism
      by which cocaine causes neurological damage is complex and involves interactions
      of the drug with several neurotransmitter systems, such as the increase of
      extracellular levels of dopamine and free radicals, and modulation of
      transcription factors. The aim of this review was to evaluate the importance of
      the dopaminergic system and the participation of inflammatory signaling in
      cocaine neurotoxicity. Our study showed that cocaine activates the transcription
      factors NF-kappaB and CREB, which regulate genes involved in cellular death. GBR
      12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and
      dopamine did not activate NF-kappaB in the same way as cocaine. However, the
      attenuation of NF-kappaB activity after the pretreatment of the cells with SCH
      23390, a D1 receptor antagonist, suggests that the activation of NF-kappaB by
      cocaine is, at least partially, due to activation of D1 receptors. NF-kappaB
      seems to have a protective role in these cells because its inhibition increased
      cellular death caused by cocaine. The increase in BDNF (brain-derived
      neurotrophic factor) mRNA can also be related to the protective role of both CREB
      and NF-kappaB transcription factors. An understanding of the mechanisms by which
      cocaine induces cell death in the brain will contribute to the development of new
      therapies for drug abusers, which can help to slow down the progress of
      degenerative processes.

PMID- 24141555
TI  - Development of a hip joint model for finite volume simulations.
AB  - This paper establishes a procedure for numerical analysis of a hip joint using
      the finite volume method. Patient-specific hip joint geometry is segmented
      directly from computed tomography and magnetic resonance imaging datasets and the
      resulting bone surfaces are processed into a form suitable for volume meshing. A
      high resolution continuum tetrahedral mesh has been generated, where a sandwich
      model approach is adopted; the bones are represented as a stiffer cortical shells
      surrounding more flexible cancellous cores. Cartilage is included as a uniform
      thickness extruded layer and the effect of layer thickness is investigated. To
      realistically position the bones, gait analysis has been performed giving the 3D
      positions of the bones for the full gait cycle. Three phases of the gait cycle
      are examined using a finite volume based custom structural contact solver
      implemented in open-source software OpenFOAM.

PMID- 24141556
TI  - Stratification of malignant pleural mesothelioma prognosis using recursive
      partitioning analysis.
AB  - PURPOSE: Prognostic factors and complicated prognostic models have been proposed
      for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM
      prognosis by using a simple model. METHODS: Patients diagnosed with MPM in the
      past 10 years (n = 122) were examined retrospectively. Data on the presence of
      chest pain, performance status (PS), asbestos exposure, smoking status, white
      blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT),
      lactate dehydronate (LD), histology, stage, and date of death or censored status
      were collected. After the factors were examined in the univariate analysis,
      recursive partitioning analysis was performed. RESULTS: Statistically significant
      factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb
      concentration, and LD. Histology, stage, PS, and Hb concentration were used in
      multivariate analysis. Stage and Hb concentration showed good statistical
      significance, whereas PS was borderline significant. The survival analyses were
      stratified into five groups by PS, stage, Hb concentration, and chest pain using
      recursive partitioning analysis. Group A comprised patients showing the most
      favourable prognoses (PS 0-2 and Hb concentration >12.1 g dL(-1) or PS 0-2 and Hb
      concentration <=12.1 g dL(-1) without pain), and group B comprised the remaining
      patients. The median overall survival in groups A and B was 563 days (95 %
      confidence interval [CI] 502-779) and 157 days (95 % CI 115-224), respectively
      (hazard ratio of 5.44 [3.46-8.53, P < 0.0001]). CONCLUSIONS: The MPM patients
      with PS 0-2 and Hb concentration >12.1 or <=12.1 g dL(-1) without chest pain had
      favourable prognoses.

PMID- 24141557
TI  - Fish anesthesia: effects of the essential oils of Hesperozygis ringens and Lippia
      alba on the biochemistry and physiology of silver catfish (Rhamdia quelen).
AB  - The anesthetic activities of the essential oils (EOs) of Hesperozygis ringens
      (EOHR) and Lippia alba (EOLA) and their effects in silver catfish (Rhamdia
      quelen) after anesthesia and recovery were investigated. Fish (32.19 +/- 1.24 g)
      were submitted to one of the following treatments for each EO: basal group,
      control, or anesthesia (150, 300, or 450 MUL L(-1) EO). After that the anesthesia
      was induced or simulated and the biometric measurements were completed, fish were
      transferred to anesthetic-free aquaria to allow for recovery. Fish were sampled
      at 0, 15, 30, 60, and 240 min after recovery. At time 0 of recovery, the
      ventilatory rate was lower in the groups anesthetized with either EO. In
      comparison with the basal group, control fish showed an increase in plasma
      glucose, aspartate aminotransferase (AST), and Na(+) levels and a reduction in
      Na(+)/K(+)-ATPase activity at 0 min of recovery. Plasma levels of ammonia and
      Na(+) were lower in the fish anesthetized with EOLA (450 MUL L(-1)) and EOHR (all
      concentrations), respectively, than in the control fish. Additionally, lactate,
      AST, alanine aminotransferase, K(+) plasma levels, and gill Na(+)/K(+)-ATPase and
      H(+)-ATPase activities were higher in the fish anesthetized with either EOHR or
      EOLA than in the control fish. The EOs promoted slight changes in silver catfish
      that enabled both an adaptive response and the recovery of most of the measured
      parameters after 240 min regardless of concentration or EO that was used. These
      findings support the use of EOHR and EOLA as anesthetics for fish. 

PMID- 24141558
TI  - Highly diastereo- and enantioselective [3+2] annulation of isatin-derived Morita
      Baylis-Hillman carbonates with trifluoropyruvate catalyzed by tertiary amines.
AB  - An enantioselective [3+2] annulation of Morita-Baylis-Hillman carbonates with
      trifluoropyruvate catalyzed by modified cinchona alkaloids was developed in good
      to excellent yields with excellent diastereo- and enantioselectivities. 

PMID- 24141559
TI  - CDCA7L promotes hepatocellular carcinoma progression by regulating the cell
      cycle.
AB  - The cell division cycle-associated 7-like protein (CDCA7L) is a recently
      identified target gene of c-Myc which can also interact with c-Myc. It is known
      to be upregulated in many tumors, however, its role in tumor progression remains
      unclear. We investigated the role of CDCA7L expression in hepatocellular
      carcinoma (HCC). We confirmed that CDCA7L is strongly upregulated in human HCC,
      and demonstrated that ectopic overexpression of CDCA7L promotes HCC cell
      proliferation and colony formation. Conversely, knockdown of CDCA7L inhibits
      these malignant phenotypes. In an in vivo model, subcutaneous transplantation of
      the tumor in nude mice showed that overexpression of CDCA7L can accelerate the
      tumor growth rate. Mechanistic analyses indicated that CDCA7L was able to
      activate the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway
      and regulate the cell cycle, thus promoting HCC progression. Collectively, these
      findings show that CDCA7L plays a role in promoting the development of HCC and
      may constitute a potential therapeutic target in HCC. 

PMID- 24141560
TI  - Update on juvenile myasthenia gravis.
AB  - PURPOSE OF REVIEW: Juvenile myasthenia gravis is a relatively rare autoimmune
      neuromuscular disorder. The pathophysiology of juvenile myasthenia gravis is
      similar to that of adult myasthenia gravis, though there remain important
      differences regarding presentation and therapeutic options. We review the
      pathophysiology, clinical presentation, and treatment options for juvenile
      myasthenia gravis. RECENT FINDINGS: Randomized clinical studies of myasthenia
      gravis have been carried out primarily in adult populations. As juvenile
      myasthenia gravis is rare, it has been difficult to collect prospective
      randomized controlled data to evaluate treatment outcomes and efficacy. A recent
      retrospective series suggests that, as in adult myasthenia gravis, thymectomy is
      a viable therapeutic option for selected cases of generalized juvenile myasthenia
      gravis. This is corroborated by the clinical experience of the authors in a
      referral center with a cohort of patients affected by juvenile myasthenia gravis
      over a number of years. SUMMARY: Recent studies illustrate that some, but not
      all, adult research on myasthenia gravis is applicable to children and
      adolescents with juvenile myasthenia gravis. Adult research can inform pediatric
      studies, but should not be regarded as a substitute for dedicated research in
      those populations.

PMID- 24141561
TI  - The development and initial validation of a virtual dripping sweat rate and a
      clothing wetness ratio for use in predictive heat strain models.
AB  - This paper applies the heat balance equation (HBE) for clothed subjects as a
      linear function of mean skin temperature (t sk ) by a new sweating efficiency
      (eta sw ) and an approximation for the thermoregulatory sweat rate. The equation
      predicting t sk in steady state conditions was derived as the solution of the HBE
      and used for a predictive heat strain scale. The heat loss from the wet clothing
      (WCL) area was identified with a new variable of 'virtual dripping sweat rate
      VDSR' (S wdr ). This is a subject's un-evaporated sweat rate in dry clothing from
      the regional sweat rate exceeding the maximum evaporative capacity, and adds the
      moisture to the clothing, reducing the intrinsic clothing insulation. The S wdr
      allowed a mass balance analysis of the wet clothing area identified as clothing
      wetness (w cl ). The w cl was derived by combining the HBE at the WCL surface
      from which the evaporation rate and skin heat loss from WCL region are given.
      Experimental results on eight young male subjects wearing typical summer
      clothing, T-shirt and trousers verified the model for predicting t sk with WCL
      thermal resistance (R cl,w ) identified as 25 % of dry clothing (R cl,d ).

PMID- 24141562
TI  - Effects of seasonal and climate variations on calves' thermal comfort and
      behaviour.
AB  - The aim of this study was to measure the effect of season and climate variations
      on thermal comfort and behaviour of 6-month-old dairy calves housed in a semi
      opened shelter to develop animal-based indicators for assessing animal thermal
      comfort. The ultimate purpose was to further exploit the use of those indicators
      to prevent thermal stress by providing appropriate care to the animals.
      Measurements were taken for winter and summer seasons. Results showed that season
      significantly influenced (P <= 0.01) the lying down behaviour of calves by
      reducing the time spent lying, from 679.9 min in winter to 554.1 min in summer.
      Moreover, season had a significant influence (P <= 0.01) on feeding behaviour. In
      detail, the total length of feeding periods was shorter in winter, 442.1 min in
      comparison to 543.5 min in summer. Time spent drinking increased significantly (P
      <= 0.001), from 11.9 min in winter to 26.9 min in summer. Furthermore, season had
      a significant influence (P <= 0.001) on self grooming behaviour which was 5.5
      times longer in duration in winter than in summer (1,336 s vs 244 s). It was
      concluded that calves' thermal comfort is affected by seasonal and climate
      variations and that this can be assessed by measuring behaviour with animal-based
      indicators, such as lying down, resting, standing up, feeding, rumination,
      drinking and self grooming. The indicators developed may be a useful tool to
      prevent animal thermal stress by providing appropriate housing and handling to
      calves under seasonal and climate challenge.

PMID- 24141563
TI  - Molecular insights: structure and dynamics of a Li ion doped organic ionic
      plastic crystal.
AB  - A molecular-level understanding of why the addition of lithium salts to Organic
      Ionic Plastic Crystals (OIPCs) produces excellent ionic conductivity is described
      for the first time. These materials are promising electrolytes for safe, robust
      lithium batteries, and have been experimentally characterised in some detail.
      Here, molecular dynamics simulations demonstrate the effects of lithium ion
      doping on both the structure and dynamics of an OIPC matrix (tetramethylammonium
      dicyanamide [TMA][DCA]) and illustrate a molecular-level transport model: in the
      plastic crystal phase lithium ions can form clusters with [DCA](-), and this
      clustering then in turn creates free volume or defect paths in the remainder of
      the lattice, which enhances ion conduction. 

PMID- 24141565
TI  - Single domain intrabodies against WASP inhibit TCR-induced immune responses in
      transgenic mice T cells.
AB  - Intrabody technology provides a novel approach to decipher the molecular
      mechanisms of protein function in cells. Single domains composed of only the
      variable regions (V(H) or V(L)) of antibodies are the smallest recombinant
      antibody fragments to be constructed thus far. In this study, we developed
      transgenic (Tg) mice expressing the V(H) or V(L) single domains derived from a
      monoclonal antibody raised against the N-terminal domain of Wiskott-Aldrich
      syndrome protein (WASP), which is an adaptor molecule in immune cells. In T cells
      from anti-WASP V(H) and V(L) single domain Tg mice, interleukin-2 production
      induced by T cell receptor (TCR) stimulation were impaired, and specific
      interaction between the WASP N-terminal domain and the Fyn SH3 domain was
      strongly inhibited by masking the binding sites in WASP. These results strongly
      suggest that the V(H)/VL single domain intrabodies are sufficient to knockdown
      the domain function of target proteins in the cytosol.

PMID- 24141566
TI  - Characterization of a cold-active beta-glucosidase from Paenibacillus
      xylanilyticus KJ-03 capable of hydrolyzing isoflavones daidzin and genistin.
AB  - Paenibacillus xylanilyticus KJ-03 isolated from konjac field, showed beta
      glucosidase activity on tryptic soy agar plate supplemented with 0.1 % esculin
      and 0.25 % ferric ammonium citrate. A genome library was constructed to obtain
      the beta-glucosidase gene and a recombinant clone, pGlc2-3 was selected. The
      2,247 bp gene encoding KJ-03 beta-glucosidase consisted of 749 amino acids. The
      deduced amino acids of BglA were 61 % homologous with that of the beta
      glucosidase from Bacillus cereus AH1272, which belongs to the glycoside hydrolase
      family 3. His-tagged beta-glucosidase was purified by using His-Trap column and
      characterized. KJ-03 beta-glucosidase was showed as a single band with about 82
      kDa on SDS-PAGE. The purified enzyme has optimal activity at 20  degrees C and pH
      7.0 using p-NPbetaG and 72 % of the maximal activity was still remaining at 10 
      degrees C. The beta-glucosidase has optimal activity at low temperatures
      indicating that it is a cold-active enzyme. The substrate specificity showed that
      the purified enzyme hydrolyzed aryl beta-glucoside substrates and isoflavones
      such as daidzin and genistin.

PMID- 24141567
TI  - Cysteinyl leukotriene receptor 1 mediates LTD4-induced activation of mouse
      microglial cells in vitro.
AB  - AIM: To investigate the roles of cysteinyl leukotriene receptors CysLT1R and
      CysLT2R in leukotriene D4 (LTD4)-induced activation of microglial cells in vitro.
      METHODS: Mouse microglial cell line BV2 was transfected with pcDNA3.1(+)-hCysLT1R
      or pcDNA3.1(+)-hCysLT2R. The expression of relevant mRNAs and proteins in the
      cells was detected using RT-PCR and Western blotting, respectively. Phagocytosis
      was determined with flow cytometry analysis. The release of interleukin-1beta (IL
      1beta) from the cells was measured using an ELISA assay. RESULTS: The expression
      of CysLT1R or CysLT2R was considerably increased in the transfected BV2 cells,
      and the receptors were mainly distributed in the plasma membrane and cytosol.
      Treatment of the cells expressing CysLT1R or CysLT2R with CysLT receptor agonist
      LTD4 (0.1-100 nmol/L) concentration-dependently enhanced the phagocytosis, and
      increased mRNA expression and release of IL-1beta. Moreover, the responses of
      hCysLT1R-BV2 cells to LTD4 were significantly larger than those of hCysLT2R-BV2
      or WT-BV2 cells. Pretreatment of hCysLT1R-BV2 cells with the selective CysLT1R
      antagonist montelukast (1 MUmol/L) significantly blocked LTD4-induced
      phagocytosis as well as the mRNA expression and release of IL-1beta, whereas the
      selective CysLT2R antagonist HAMI 3379 (1 MUmol/L) had no such effects.
      CONCLUSION: CysLT1R mediates LTD4-induced activation of BV2 cells, suggesting
      that CysLT1R antagonists may exert anti-inflammatory activity in brain diseases.

PMID- 24141568
TI  - Oligomannurarate sulfate inhibits CXCL12/SDF-1-mediated proliferation and
      invasion of human tumor cells in vitro.
AB  - AIM: JG6 is a novel marine-derived oligosaccharide that has shown to inhibit
      angiogenesis and tumor metastasis. In this study, we sought to identify the
      potential target responsible for the anti-cancer activity of JG6. METHODS: Human
      liver cancer cell line Bel-7402 and human cervical cancer cell line HeLa were
      examined. CXCL12-stimulated cell proliferation and migration were determined
      using a CCK-8 kit and a transwell assay, respectively. Western blotting was
      performed to examine the changes in CXCL12/CXCR4 axis. Molecular docking and
      surface plasmon resonance (SPR) were performed to characterize the possible
      interaction between JG6 and the CXCL12/CXCR4 axis. RESULTS: Treatment with CXCL12
      potently stimulated the proliferation and migration in both Bel-7402 and HeLa
      cells. Co-treatment of the cells with JG6 (10, 50 and 100 MUg/mL) dose
      dependently impeded the CXCL12-stimulated cell proliferation and migration.
      Furthermore, CXCL12 rapidly induced phosphorylation of AKT, ERK, FAK and Paxillin
      in Bel-7402 and HeLa cells, whereas pretreatment with JG6 dose-dependently
      inhibited the CXCL12-induced phosphorylation of these proteins. The SPR assay
      showed that JG6 bound to CXCL12 with a high affinity. In molecular docking study,
      JG6 appeared to interact with CXCL12 via multiple polar interactions, including 6
      ionic bonds and 7 hydrogen bonds. CONCLUSION: Inhibition of the CXCL12/CXCR4 axis
      by JG6 may account for its anticancer activity.

PMID- 24141569
TI  - Linear- and nonlinear-electromyographic analysis of supracutaneous vibration
      stimuli of the forearm using diverse frequencies and considering skin
      physiological properties.
AB  - Numerous studies have reported the efficacy of vibration in sensory feedback or
      substitution devices for users of myoelectric hand prostheses. Although most
      myoelectric hand prostheses are presently manipulated by a surface electromyogram
      (sEMG), only a few studies have been conducted on the effect of vibration on an
      sEMG. This study aimed to determine whether vibration stimulation affects the
      linear and nonlinear properties of surface electromyography (sEMG) considering
      the skin properties. The vibration stimuli, with frequencies ranging from 37 to
      258 Hz, were applied to the proximal part of the arms of the eight female and
      seven male subjects. The skinfold thickness, hardness, and vibration threshold at
      the stimuli loci were measured. The root mean square (rms) and fractal dimension
      (DF) of the sEMG were measured at a distance of 1 cm in the upward direction from
      the stimuli loci. Above 223 Hz there were no differences between the rms of the
      genders in between the vibration stimuli (p > 0.05). Moreover, no differences
      were observed between the DF of the genders for any frequency (p > 0.05). Above
      149 Hz, there were correlations between the rms and the skin hardness in the
      females. Otherwise, no correlations were observed between the rms and DF and the
      skin properties in both genders for most of the frequencies (all p > 0.05). These
      results suggest that vibration stimuli affect the linear properties of the sEMG,
      but not the nonlinear properties.

PMID- 24141570
TI  - Cannabinoid receptor activation prevents the effects of chronic mild stress on
      emotional learning and LTP in a rat model of depression.
AB  - Most psychiatric disorders are characterized by emotional memory or learning
      disturbances. Chronic mild stress (CMS) is a common animal model for stress
      induced depression. Here we examined whether 3 days of treatment using the CB1/2
      receptor agonist WIN55,212-2 could ameliorate the effects of CMS on emotional
      learning (ie, conditioned avoidance and extinction), long-term potentiation (LTP)
      in the hippocampal-accumbens pathway, and depression-like symptoms (ie, coping
      with stress behavior, anhedonia, and weight changes). We also examined whether
      the ameliorating effects of WIN55,212-2 on behavior and physiology after CMS are
      mediated by CB1 and glucocorticoid receptors (GRs). Rats were exposed to CMS or
      handled on days 1-21. The agonist WIN55,212-2 or vehicle were administered on
      days 19-21 (IP; 0.5 mg/kg) and behavioral and electrophysiological measures were
      taken on days 23 and 28. The CB1 receptor antagonist AM251 (IP; 0.3 mg/kg) or the
      GR antagonist RU-38486 (IP; 10 mg/kg) were co-administered with WIN55,212-2. Our
      results show that CMS significantly modified physiological and behavioral
      reactions, as observed by the impairment in avoidance extinction and LTP in the
      hippocampal-accumbens pathway, and the alterations in depression-like symptoms,
      such as coping with stress behavior, weight gain, and sucrose consumption. The
      most significant effect observed in this study was that 3 days of WIN55,212-2
      administration prevented the CMS-induced alterations in emotional memory (ie,
      extinction) and plasticity. This effect was mediated by CB1 receptors as the CB1
      receptor antagonist AM251 prevented the ameliorating effects of WIN55,212-2 on
      extinction and LTP. The GR antagonist RU-38486 also prevented the CMS-induced
      alterations in extinction and plasticity, and when co-administered with WIN55,212
      2, the preventive effects after CMS were maintained. The findings suggest that
      enhancing cannabinoid signaling could represent a novel approach to the treatment
      of cognitive deficits that accompany stress-related depression.

PMID- 24141571
TI  - Fine mapping on chromosome 13q32-34 and brain expression analysis implicates
      MYO16 in schizophrenia.
AB  - We previously reported linkage of schizophrenia and schizoaffective disorder to
      13q32-34 in the European descent Afrikaner population from South Africa. The
      nature of genetic variation underlying linkage peaks in psychiatric disorders
      remains largely unknown and both rare and common variants may be contributing.
      Here, we examine the contribution of common variants located under the 13q32-34
      linkage region. We used densely spaced SNPs to fine map the linkage peak region
      using both a discovery sample of 415 families and a meta-analysis incorporating
      two additional replication family samples. In a second phase of the study, we use
      one family-based data set with 237 families and independent case-control data
      sets for fine mapping of the common variant association signal using HapMap SNPs.
      We report a significant association with a genetic variant (rs9583277) within the
      gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated
      in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap
      variation within MYO16 in a second set of Afrikaner families and additional case
      control data sets of European descent highlighted a region across introns 2-6 as
      the most likely region to harbor common MYO16 risk variants. Expression analysis
      revealed a significant increase in the level of MYO16 expression in the brains of
      schizophrenia patients. Our results suggest that common variation within MYO16
      may contribute to the genetic liability to schizophrenia. 

PMID- 24141573
TI  - Characterization of the genetic changes in a multi-generational pedigree of an
      elite Canadian soybean cultivar.
AB  - Genotyping through the pedigrees of elite soybean [Glycine max (L.) Merr.]
      cultivars developed by a breeding program represents an opportunity to explore
      and characterize various molecular and genetic changes that are a direct result
      of long-term selection by soybean breeders. For soybeans bred for Ontario Canada,
      one such elite cultivar was OAC Bayfield, which had exceptional commercial
      success as well as being a parent of a number of successful cultivars developed
      by multiple independent breeding programs. A total of 42 genotypes from six
      different breeding programs, comprising the multi-generational pedigree of OAC
      Bayfield were genotyped with molecular markers and chromosomal inheritance was
      tracked throughout the pedigree. Cluster analysis showed high congruence with the
      known pedigree and identified three distinct ancestral groups. The ancestral
      genotypes contained the majority of the rare alleles, with the cultivar CNS
      having the greatest number of unique alleles. The graphical genotype profile for
      the 20 chromosomes revealed conserved allelic composition which has been
      assembled in certain chromosomes in the form of specific linkage blocks, which
      were either a result of recombination involving ancestral linkage blocks or
      linkage blocks introduced from the cultivar Fiskeby-V. The identification of
      highly structured, conserved genomic regions are important for future breeding
      efforts as they are indicators of preferentially selected regions, or conversely,
      may be a contributing factor to low genetic gains due to mass fixation across a
      breeding program's germplasm. 

PMID- 24141574
TI  - Dispelling misconceptions about developmentally challenged children.

PMID- 24141572
TI  - Effect of a dienogest for an experimental three-dimensional endometrial culture
      model for endometriosis.
AB  - The pathogenesis of endometriosis remains poorly understood at least in part
      because early stages of the disease process are difficult to investigate.
      Previous studies have proposed a three-dimensional fibrin matrix culture model to
      study human endometriosis. We examined the ultrastructural features of the
      endometriosis in this model and assessed the effect of a progestin on endometrial
      outgrowth and apoptosis in this culture system. Endometrial explants were placed
      in three-dimensional fibrin matrix culture and treated with and without various
      concentrations of the progestin dienogest. By the second week, endometrial gland
      like formation was established in outgrowths both attached to and at a distance
      from the explants. These cells formed a combination of clumps and tubular
      monolayers surrounding a central cavity. Electron microscopy demonstrated that
      these cells are polarized with microvilli on the apical surface, desmosome-like
      structures, and basement membrane; features consistent with glandular epithelial
      cells. Outgrowth of endometrial stromal cells and glandular formation was
      impaired in response to dienogest in a dose-dependent manner. Our study shows
      that the human endometrial explants cultured in three-dimensional fibrin matrix
      establish outgrowths that ultrastructurally resemble ectopic endometrial
      implants. This model may provide insight into the cellular processes leading to
      endometriosis formation and enables screening of therapeutic compounds. 

PMID- 24141576
TI  - "Walking the dog" to enhance postoperative recovery.
AB  - BACKGROUND: Nurses on an adult surgical unit perceived a decrease in patients'
      mobility and an increase in postoperative complications, which led to an
      initiative to motivate patients to ambulate. RESEARCH QUESTIONS: The questions
      addressed in this study refer to adult patients having surgery: Is there a
      relationship between ambulation and length of stay (LOS)? Did "walking the dog"
      affect how early and how many times they ambulated? Did "walking the dog" affect
      the incidence of postoperative complications? METHODS: Photos of dogs were made
      available and patients were encouraged to "walk the dog" at least three times
      daily. CONCLUSIONS: Although this intervention didn't lead to a significant
      difference in LOS or complications, patients anecdotally reported an increased
      motivation to ambulate.

PMID- 24141577
TI  - Anaphylaxis.

PMID- 24141579
TI  - Help family caregivers in the "sandwich generation".

PMID- 24141582
TI  - All I want is a banana.

PMID- 24141583
TI  - Responding to an active shooter and other threats of violence.

PMID- 24141585
TI  - Making a case for nurse empowerment.

PMID- 24141586
TI  - Nurses know how to manage fever, but what about the shivering?

PMID- 24141587
TI  - Urinary incontinence in adults.

PMID- 24141588
TI  - Codeine for children: weighing the risks.

PMID- 24141589
TI  - Pressure ulcer alert!

PMID- 24141590
TI  - Understanding vancomycin levels.

PMID- 24141591
TI  - Using distraction techniques with children.

PMID- 24141593
TI  - A technique for estimating the occlusion effect for frequencies below 125 Hz.
AB  - OBJECTIVES: The level of bone-conducted sound in the auditory meatus is increased
      at low frequencies by occlusion of the meatus, for example, by the earmold of a
      hearing aid (HA). Physical measures of this "occlusion effect" (OE) require
      vibration of the skull. In previous research, either self-voicing or audiometric
      bone conduction vibrators were used to produce this vibration, with the result
      that the OE could not be measured for frequencies below 125 Hz. However,
      frequencies below this can be important for music perception by HA users. The
      objective was to develop and evaluate a method that gives a lower-bound estimate
      of the OE for frequencies below 125 Hz. DESIGN: A low-noise amplifier with
      extended low-frequency response was used to record the output of a miniature
      microphone inserted into the meatus of participants. The signal came from sounds
      of the heartbeat and blood flow of the participant, transmitted via bone
      conduction through the walls of the meatus. A simultaneous recording was made of
      the carotid pulse to permit time-locked averaging (and hence noise reduction) of
      the microphone signal. Recordings were made from 7 otologically and
      audiometrically normal participants, using clinical probe tips to produce the
      occlusion. Recordings were also made from an overlapping group of 9 participants,
      using fast-setting impression material to provide a more consistent degree of
      occlusion. The difference in level of the recorded signal for unoccluded and
      occluded conditions provided a lower bound for the magnitude of the OE. RESULTS:
      The mean OE increased with decreasing frequency, reaching a plateau of about 40
      dB for frequencies below 40 Hz. For some individual recordings, the OE reached 50
      dB for frequencies below 20 Hz. With occlusion, the heartbeat became audible for
      most participants. CONCLUSIONS: The OE can be very large at low frequencies. The
      use of HAs with closed fittings, which may be used either to prevent acoustic
      feedback or to allow amplification of low frequencies, may lead to an
      unacceptable OE. The authors suggest reducing the OE with the use of a seal deep
      in the meatus, where the wall of the meatus is more rigid.

PMID- 24141594
TI  - Fundamental frequency information for speech recognition via bimodal stimulation:
      cochlear implant in one ear and hearing aid in the other.
AB  - OBJECTIVE: The aim of this study was to examine the role of fundamental frequency
      (F0) information in improving speech perception of individuals with a cochlear
      implant (CI) who use a contralateral hearing aid (HA). The authors hypothesized
      that in bilateral-bimodal (CI/HA) users the perception of natural prosody speech
      would be superior to the perception of speech with monotonic flattened F0
      contour, whereas in unilateral CI users the perception of both speech signals
      would be similar. They also hypothesized that in the CI/HA listening condition
      the speech perception scores would improve as a function of the magnitude of the
      difference between the F0 characteristics of the target speech signal and the F0
      characteristics of the competitors, whereas in the CI-alone condition such a
      pattern would not be recognized, or at least not as clearly. DESIGN: Two tests
      were administered to 29 experienced CI/HA adult users who, regardless of their
      residual hearing or speech perception abilities, had chosen to continue using an
      HA in the nonimplanted ear for at least 75% of their waking hours. In the first
      test, the difference between the perception of speech characterized by natural
      prosody and speech characterized by monotonic flattened F0 contour was assessed
      in the presence of babble noise produced by three competing male talkers. In the
      second test the perception of semantically unpredictable sentences was evaluated
      in the presence of a competing reversed speech sentence spoken by different
      single talkers with different F0 characteristics. Each test was carried out under
      two listening conditions: CI alone and CI/HA. RESULTS: Under both listening
      conditions, the perception of speech characterized by natural prosody was
      significantly better than the perception of speech in which monotonic F0 contour
      was flattened. Differences between the scores for natural prosody and for
      monotonic flattened F0 speech contour were significantly greater, however, in the
      CI/HA condition than with CI alone. In the second test, the overall scores for
      perception of semantically unpredictable sentences in the presence of all
      competitors were higher in the CI/HA condition in the presence of all
      competitors. In both listening conditions, scores increased significantly with
      increasing difference between the F0 characteristics of the target speech signal
      and the F0 characteristics of the competitor. CONCLUSIONS: The higher scores
      obtained in the CI/HA condition than with CI alone in both of the task-specific
      tests suggested that the use of a contralateral HA provides improved low
      frequency information, resulting in better performance by the CI/HA users.

PMID- 24141595
TI  - Comparative transcriptional analysis reveals differential gene expression between
      Sand Daffodil tissues.
AB  - Sand Daffodil (Pancratium maritimum) is a world-wide endangered Amayllidaceae
      species and represents an important anti-cancer medicinal resource due to
      alkaloids production. Despite its increasing pharmaceutical importance, there are
      not molecular resources that can be utilized toward improving genetic traits. In
      our research, the suppression subtractive hybridization (SSH) method conducted to
      generate large-scale expressed sequence tags (EST), was designed to identify gene
      candidates related to the morphological and physiological differences between the
      two tissues, leaves and bulbs, since lycorine, the main anti-cancer compound, is
      there synthesized. We focused on identification of transcripts in different
      tissues from Sand Daffodil using PCR-based suppression SSH to identify genes
      involved in global pathway control. Sequencing of 2,000 differentially screened
      clones from the SSH libraries resulted in 136 unigenes. Functional annotation and
      gene ontology analysis of up-regulated EST libraries showed several known
      biosynthetic genes and novel transcripts that may be involved in signaling,
      cellular transport, or metabolism. Real time RT-PCR analysis of a set of 8
      candidate genes further confirmed the differential gene expression. 

PMID- 24141596
TI  - Oleifolioside B-mediated autophagy promotes apoptosis in A549 human non-small
      cell lung cancer cells.
AB  - The biochemical mechanisms of cell death by oleifolioside B (OB), a cycloartane
      type triterpene glycoside isolated from Dendropanax morbifera Leveille, were
      investigated in A549 human lung carcinoma cells. Our data indicated that exposure
      to OB led to caspase activation and typical features of apoptosis; however,
      apoptotic cell death was not prevented by z-VAD-fmk, a pan-caspase inhibitor,
      demonstrating that OB-induced apoptosis was independent of caspase activation.
      Subsequently, we found that OB increased autophagy, as indicated by an increase
      in monodansylcadaverine fluorescent dye-labeled autophagosome formation and in
      the levels of the autophagic form of microtubule-associated protein 1 light chain
      3 and Atg3, an autophagy-specific gene, which is associated with inhibiting
      phospho-nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However,
      pretreatment with bafilomycin A1, an autophagy inhibitor, attenuated OB-induced
      apoptosis and dephosphorylation of Nrf2. The data suggest that OB-induced
      autophagy functions as a death mechanism in A549 cells and OB has potential as a
      novel anticancer agent capable of targeting apoptotic and autophagic cell death
      and the Nrf2 signaling pathway.

PMID- 24141597
TI  - Factors associated with pregabalin dispensing at higher than the approved maximum
      dose.
AB  - PURPOSE: Concerns have been raised about the abuse potential of pregabalin.
      Therefore, the aim of our study was to characterize patients dispensed pregabalin
      at higher than the maximum allowed dose in a cohort study based on data extracted
      from Swedish national registers. METHODS: All patients dispensed at least three
      prescriptions of pregabalin between July 2006 and December 2009 were included (n
      = 48,550). The daily dose was defined as the amount of pregabalin dispensed
      divided by the number of days between the second and third dispensings.
      Associations between sociodemographic and clinical variables and dispensing
      pregabalin at a dose exceeding the maximum daily allowed dose (600 mg) were
      investigated in multivariate regression models. RESULTS: Of the patients
      dispensed pregabalin during the study period, 8.5 % were dispensed a dose that
      exceeded the maximum daily allowed dose. A previous addictive disorder drug
      treatment or diagnosis was present in 20 and 31 % of patients dispensed
      pregabalin within and exceeding the recommended dose range, respectively. Our
      analysis revealed that those patients at increased risk of being dispensed
      pregabalin at higher than the maximum allowed dose were male [adjusted odds ratio
      (aOR) 1.40, 95 % confidence interval (CI) 1.31-1.49], were between 18 and 29
      years of age compared with those aged >=65 years (aOR 1.62, 95 % CI 1.45-1.82),
      had a low income (aOR 1.24, 95 % CI 1.10-1.40), had epilepsy compared with no
      diagnosis (aOR 1.41, 95 % CI 1.10-1.81), had a previous substance use disorder
      treatment or diagnosis (aOR 1.41, 95 % CI 1.31-1.52) or had previously been
      dispensed high doses of drugs with abuse potential (aOR 1.77, 95 % CI 1.62-1.94).
      CONCLUSION: Based on our results we conclude that patients at a high risk of
      addiction and patients with epilepsy are more likely to be dispensed pregabalin
      at higher than the maximum approved daily dose.

PMID- 24141599
TI  - Surfactant free most probable TiO2 nanostructures via hydrothermal and its dye
      sensitized solar cell properties.
AB  - Tailoring the nano-morphology and nano-architecture of titanium dioxide (TiO2) is
      the most important task in the third generation solar cells (Dye sensitized solar
      cells/Quantum dot sensitized solar cells) (DSSCs/QDSSCs). In this article we
      present complete study of surfactant free synthesis of TiO2 nanostructures by a
      simple and promising hydrothermal route. The plethora of nanostructures like
      nanoparticles clusters, 1D tetragonal nanorods, 3D dendrites containing nanorods
      having <30 nm diameter and 3D hollow urchin like have been synthesized. These
      nanostructures possess effective large surface area and thus useful in DSSCs. In
      the present work, 7.16% power conversion efficiency has been demonstrated for 3D
      dendritic hollow urchin like morphology. Our synthetic strategy provides an
      effective solution for surfactant free synthesis of efficient TiO2
      nanoarchitectures.

PMID- 24141601
TI  - Flexible, low-temperature, solution processed ZnO-based perovskite solid state
      solar cells.
AB  - A ZnO compact layer formed by electrodeposition and ZnO nanorods grown by
      chemical bath deposition (CBD) allow the processing of low-temperature, solution
      based and flexible solid state perovskite CH3NH3PbI3 solar cells. Conversion
      efficiencies of 8.90% were achieved on rigid substrates while the flexible ones
      yielded 2.62%. 

PMID- 24141603
TI  - Gas-phase spectroscopy of protonated adenine, adenosine 5'-monophosphate and
      monohydrated ions.
AB  - Microsolvation of chromophore ions commonly has large effects on their electronic
      structure and as a result on their optical absorption spectra. Here spectroscopy
      of protonated adenine (AdeH(+)) and its complex with one water molecule isolated
      in vacuo was done using a home-built mass spectrometer in combination with a
      tuneable pulsed laser system. Experiments also included the protonated adenosine
      5'-monophosphate nucleotide (AMPH(+)). In the case of bare AdeH(+) ions, one
      photon absorption leads to four dominant fragment ions corresponding to ammonium
      and ions formed after loss of either NH3, HCN, or NH2CN. The yields of these were
      measured as a function of the wavelength of the light from 210 nm to 300 nm, and
      they were combined to obtain the total photoinduced dissociation at each
      wavelength (i.e., action spectrum). A broad band between 230 nm and 290 nm and
      the tail of a band with maximum below 210 nm (high-energy band) are seen. In the
      case of AdeH(+)(H2O), the dominant dissociation channel after photoexcitation in
      the low-energy band was simply loss of H2O while photodissociation of protonated
      AMP revealed two dominant dissociation channels associated with the formation of
      either AdeH(+) or loss of H3PO4. The action spectra of AdeH(+), AdeH(+)(H2O), and
      AMPH(+) are almost identical in the 230-290 nm region, and they resemble the
      absorption spectrum of protonated adenine in aqueous solution recorded at low pH.
      Hence from our work it is firmly established that the lowest-energy transitions
      are independent of the surroundings. 

PMID- 24141604
TI  - Chronic disease care in remote Aboriginal Australia has been transformed.

PMID- 24141605
TI  - What's next for public health in a post-Bloomberg NYC?

PMID- 24141606
TI  - Nuffield Council opens consultation on use of personal biological and health
      data.

PMID- 24141607
TI  - Late amendment to Care Bill "moves the goalposts" in fight over Lewisham
      Hospital, lawyer says.

PMID- 24141602
TI  - Current concepts in clinical radiation oncology.
AB  - Based on its potent capacity to induce tumor cell death and to abrogate
      clonogenic survival, radiotherapy is a key part of multimodal cancer treatment
      approaches. Numerous clinical trials have documented the clear correlation
      between improved local control and increased overall survival. However, despite
      all progress, the efficacy of radiation-based treatment approaches is still
      limited by different technological, biological, and clinical constraints. In
      principle, the following major issues can be distinguished: (1) The intrinsic
      radiation resistance of several tumors is higher than that of the surrounding
      normal tissue, (2) the true patho-anatomical borders of tumors or areas at risk
      are not perfectly identifiable, (3) the treatment volume cannot be adjusted
      properly during a given treatment series, and (4) the individual heterogeneity in
      terms of tumor and normal tissue responses toward irradiation is immense. At
      present, research efforts in radiation oncology follow three major tracks, in
      order to address these limitations: (1) implementation of molecularly targeted
      agents and 'omics'-based screening and stratification procedures, (2) improvement
      of treatment planning, imaging, and accuracy of dose application, and (3)
      clinical implementation of other types of radiation, including protons and heavy
      ions. Several of these strategies have already revealed promising improvements
      with regard to clinical outcome. Nevertheless, many open questions remain with
      individualization of treatment approaches being a key problem. In the present
      review, the current status of radiation-based cancer treatment with particular
      focus on novel aspects and developments that will influence the field of
      radiation oncology in the near future is summarized and discussed. 

PMID- 24141608
TI  - Transcranial direct current stimulation and repetitive transcranial magnetic
      stimulation in consultation-liaison psychiatry.
AB  - Patients with clinical diseases often present psychiatric conditions whose
      pharmacological treatment is hampered due to hazardous interactions with the
      clinical treatment and/or disease. This is particularly relevant for major
      depressive disorder, the most common psychiatric disorder in the general
      hospital. In this context, nonpharmacological interventions could be useful
      therapies; and, among those, noninvasive brain stimulation (NIBS) might be an
      interesting option. The main methods of NIBS are repetitive transcranial magnetic
      stimulation (rTMS), which was recently approved as a nonresearch treatment for
      some psychiatric conditions, and transcranial direct current stimulation (tDCS),
      a technique that is currently limited to research scenarios but has shown
      promising results. Therefore, our aim was to review the main medical conditions
      associated with high depression rates, the main obstacles for depression
      treatment, and whether these therapies could be a useful intervention for such
      conditions. We found that depression is an important and prevalent comorbidity in
      a variety of diseases such as epilepsy, stroke, Parkinson's disease, myocardial
      infarction, cancer, and in other conditions such as pregnancy and in patients
      without enteral access. We found that treatment of depression is often suboptimal
      within the above contexts and that rTMS and tDCS therapies have been
      insufficiently appraised. We discuss whether rTMS and tDCS could have a
      significant impact in treating depression that develops within a clinical
      context, considering its unique characteristics such as the absence of
      pharmacological interactions, the use of a nonenteral route, and as an
      augmentation therapy for antidepressants.

PMID- 24141610
TI  - Adenovirus-mediated siRNA targeting TNF-alpha and overexpression of bone
      morphogenetic protein-2 promotes early osteoblast differentiation on a cell model
      of Ti particle-induced inflammatory response in vitro.
AB  - Wear particles are phagocytosed by macrophages and other inflammatory cells,
      resulting in cellular activation and release of proinflammatory factors, which
      cause periprosthetic osteolysis and subsequent aseptic loosening, the most common
      causes of total joint arthroplasty failure. During this pathological process,
      tumor necrosis factor-alpha (TNF-alpha) plays an important role in wear-particle
      induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying
      both target genes [TNF-alpha small interfering RNA (TNF-alpha-siRNA) and bone
      morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7
      macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene
      BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-alpha
      gene on cells, was treated with titanium (Ti) particles that were assessed by
      real-time PCR and Western blot. We showed that recombinant adenovirus (Ad
      siTNFalpha-BMP-2) can induce osteoblast differentiation when treated with
      conditioned medium (CM) containing RAW264.7 macrophages challenged with a
      combination of Ti particles and Ad-siTNFalpha-BMP-2 (Ti-ad CM) assessed by
      alkaline phosphatase activity. The receptor activator of nuclear factor-kappaB
      ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM
      in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti
      particles (Ti CM). We suggest that Ad-siTNFalpha-BMP-2 induced osteoblast
      differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle
      induced inflammatory response, which may provide a novel approach for the
      treatment of periprosthetic osteolysis. 

PMID- 24141609
TI  - Extracellular vesicles: structure, function, and potential clinical uses in renal
      diseases.
AB  - Interest in the role of extracellular vesicles in various diseases including
      cancer has been increasing. Extracellular vesicles include microvesicles,
      exosomes, apoptotic bodies, and argosomes, and are classified by size, content,
      synthesis, and function. Currently, the best characterized are exosomes and
      microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular
      communication regardless of the distance between them. They are found in various
      biological fluids such as plasma, serum, and breast milk, and are formed from
      multivesicular bodies through the inward budding of the endosome membrane.
      Microvesicles are 100-1000 nm vesicles released from the cell by the outward
      budding of the plasma membrane. The therapeutic potential of extracellular
      vesicles is very broad, with applications including a route of drug delivery and
      as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may
      be used for treatment of many diseases including kidney diseases. This review
      highlights mechanisms of synthesis and function, and the potential uses of well
      characterized extracellular vesicles, mainly exosomes, with a special focus on
      renal functions and diseases. 

PMID- 24141611
TI  - The left lung is preferentially targeted during experimental
      paracoccidioidomycosis in C57BL/6 mice.
AB  - Paracoccidioidomycosis (PCM) is a chronic systemic mycosis caused by the
      inhalation of the thermally dimorphic fungus Paracoccidioides brasiliensis as
      well as the recently described P. lutzii. Because the primary infection occurs in
      the lungs, we investigated the differential involvement of the right and left
      lungs in experimental P. brasiliensis infection. Lungs were collected from
      C57BL/6 mice at 70 days after intravenous infection with 1*106 yeast cells of a
      virulent strain of P. brasiliensis (Pb18). The left lung, which in mice is
      smaller and has fewer lobes than the right lung, yielded increased fungal
      recovery associated with a predominant interleukin-4 response and diminished
      synthesis of interferon-gamma and nitric oxide compared with the right lung. Our
      data indicate differential involvement of the right and left lungs during
      experimental PCM. This knowledge emphasizes the need for an accurate,
      standardized protocol for tissue collection during studies of experimental P.
      brasiliensis infection, since experiments using the same lungs favor the
      collection of comparable data among different mice. 

PMID- 24141612
TI  - Sleep pattern and learning in knockdown mice with reduced cholinergic
      neurotransmission.
AB  - Impaired cholinergic neurotransmission can affect memory formation and influence
      sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a
      deficient vesicular acetylcholine transporter (VAChT) system, previously
      characterized as presenting reduced acetylcholine release and cognitive and
      behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to
      evaluate the SWC pattern during light and dark phases in VAChT knockdown
      heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated
      for sleep efficiency, total amount and mean duration of slow-wave, intermediate
      and paradoxical sleep, as well as the number of awakenings from sleep. After
      recording SWC, contextual fear-conditioning tests were used as an acetylcholine
      dependent learning paradigm. The results showed that sleep efficiency in VAChT
      KDHET animals was similar to that of WT mice, but that the SWC was more
      fragmented. Fragmentation was characterized by an increase in the number of
      awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed
      poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4+/
      3.1 and 44.5+/-3.3 s for WT and VAChT-KDHET animals, respectively), which was
      followed by a 45% reduction in the number of paradoxical sleep episodes after the
      training session. Taken together, the results show that reduced cholinergic
      transmission led to sleep fragmentation and learning impairment. We discuss the
      results on the basis of cholinergic plasticity and its relevance to sleep
      homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test
      cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

PMID- 24141613
TI  - Differential effects of aging on spatial contrast sensitivity to linear and polar
      sine-wave gratings.
AB  - Changes in visual function beyond high-contrast acuity are known to take place
      during normal aging. We determined whether sensitivity to linear sine-wave
      gratings and to an elementary stimulus preferentially processed in extrastriate
      areas could be distinctively affected by aging. We measured spatial contrast
      sensitivity twice for concentric polar (Bessel) and vertical linear gratings of
      0.6, 2.5, 5, and 20 cycles per degree (cpd) in two age groups (20-30 and 60-70
      years). All participants were free of identifiable ocular disease and had normal
      or corrected-to-normal visual acuity. Participants were more sensitive to
      Cartesian than to polar gratings in all frequencies tested, and the younger adult
      group was more sensitive to all stimuli tested. Significant differences between
      sensitivities of the two groups were found for linear (only 20 cpd; P<0.01) and
      polar gratings (all frequencies tested; P<0.01). The young adult group was
      significantly more sensitive to linear than to circular gratings in the 20 cpd
      frequency. The older adult group was significantly more sensitive to linear than
      to circular gratings in all spatial frequencies, except in the 20 cpd frequency.
      The results suggest that sensitivity to the two kinds of stimuli is affected
      differently by aging. We suggest that neural changes in the aging brain are
      important determinants of this difference and discuss the results according to
      current models of human aging. 

PMID- 24141614
TI  - Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as
      determinants of salt-sensitive hypertension: a reverse translational rat study.
AB  - This study determined whether clinical salt-sensitive hypertension (cSSHT)
      results from the interaction between partial arterial baroreceptor impairment and
      a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial
      pressure (MAP) of conscious male Wistar ChR003 rats was measured once before
      (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD),
      following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa
      diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal
      medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H
      oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15)
      groups of S-I, LNaMAP-pdMAP was 10.5+/-2.1 vs 23+/-2.1 mmHg (P<0.001), and the
      salt-sensitivity index (SSi; HNaMAP-LNaMAP) was 6.0+/-1.9 vs 12.7+/-1.9 mmHg
      (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36%
      were salt sensitive (SSi>=10 mmHg), whereas in the AD group ~50% showed cSSHT. A
      45% reduction in pNOB (P<=0.004) was observed in both groups in dietary transit.
      RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II,
      P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a
      renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008)
      increases the likelihood of developing cSSHT. Translationally, these findings
      help to explain why subjects with clinical salt-sensitive normotension may
      transition to cSSHT.

PMID- 24141615
TI  - Morphometric evaluation of nitric oxide synthase isoforms and their cytokine
      regulators predict pulmonary dysfunction and survival in systemic sclerosis.
AB  - Because histopathological changes in the lungs of patients with systemic
      sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume
      that this interaction can be characterized by analyzing the expression of
      proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI
      1) synthesis. To validate the importance of alveolar-vascular interactions and to
      explore the quantitative relationship between these factors and other clinical
      data, we studied these markers in 23 cases of SSc nonspecific interstitial
      pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate
      the amount of cells in alveolar septa and vessels staining for NO synthase (NOS)
      and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP,
      pulmonary function tests, and survival time until death. General linear model
      analysis demonstrated that staining for septal inducible NOS (iNOS) related
      significantly to staining of septal cells for interleukin (IL)-4 and to septal IL
      13. In univariate analysis, higher levels of septal and vascular cells staining
      for iNOS were associated with a smaller percentage of septal and vascular cells
      expressing fibroblast growth factor and myofibroblast proliferation,
      respectively. Multivariate Cox model analysis demonstrated that, after
      controlling for SSc-NSIP histological patterns, just three variables were
      significantly associated with survival time: septal iNOS (P=0.04), septal IL-13
      (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented
      NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible
      functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4
      staining in alveolar septa and vessels provides a possible independent diagnostic
      measure for the degree of pulmonary dysfunction and fibrosis with an impact on
      the survival of patients with SSc. 

PMID- 24141616
TI  - Nasal CPAP in the delivery room for newborns with extremely low birth weight in a
      hospital in a developing country.
AB  - The objective of this study was to determine the feasibility of the use of
      continuous positive airway pressure installed prophylactically in the delivery
      room (DR-CPAP), for infants with a birth weight between 500 and 1000 g in
      settings with limited resources. During 23 months, infants with a birth weight
      between 500 and 1000 g consecutively received DR-CPAP. A total of 33 infants with
      low birth weight were enrolled, 16 (48.5%) were females. Only 14 (42.4%) received
      antenatal corticosteroids and only 2 of those 14 (14.3%) infants weighing 500-750
      g were not intubated in the delivery room, and apnea was given as the reason for
      intubation of these patients. Of the 19 infants in the 751-1000 g weight range, 9
      (47.4%) were intubated in the delivery room, 6 due to apnea and 3 due to
      respiratory discomfort. For DR-CPAP to be successful, it is probably necessary
      for preterm babies to be more prepared at birth to withstand the respiratory
      effort without the need for intubation. Antenatal corticosteroids and better
      prenatal monitoring are fundamental for success of DR-CPAP. 

PMID- 24141617
TI  - Relationship between genetic mutation variations and acute-phase reactants in the
      attack-free period of children diagnosed with familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease
      characterized by chronic inflammation. This study investigated the relationship
      between acute-phase reactants and gene mutations in attack-free periods of
      childhood FMF. Patients diagnosed with FMF were divided into four groups based on
      genetic features: no mutation, homozygous, heterozygous, and compound
      heterozygous. These groups were monitored for 2 years, and blood samples were
      collected every 6 months during attack-free periods. Erythrocyte sedimentation
      rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A
      disease severity score was determined for each patient. Mean values for
      erythrocyte sedimentation rate and fibrinogen were significantly different in the
      homozygous group. White blood cell count and C-reactive protein were similar
      between the groups. Disease severity score was higher in patients with the M694V
      mutation than in individuals without the mutation, as well as in those with other
      mutation groups. Periodic follow-up of patients with FMF MEFV mutations in
      subjects with acute-phase reactants may be useful in the prevention of morbidity.

PMID- 24141618
TI  - Probing N6-methyladenosine RNA modification status at single nucleotide
      resolution in mRNA and long noncoding RNA.
AB  - N(6)-methyladenosine (m(6)A) is the most abundant modification in mammalian mRNA
      and long noncoding RNA (lncRNA). Recent discoveries of two m(6)A demethylases and
      cell-type and cell-state-dependent m(6)A patterns indicate that m(6)A
      modifications are highly dynamic and likely play important biological roles for
      RNA akin to DNA methylation or histone modification. Proposed functions for m(6)A
      modification include mRNA splicing, export, stability, and immune tolerance; but
      m(6)A studies have been hindered by the lack of methods for its identification at
      single nucleotide resolution. Here, we develop a method that accurately
      determines m(6)A status at any site in mRNA/lncRNA, termed site-specific cleavage
      and radioactive-labeling followed by ligation-assisted extraction and thin-layer
      chromatography (SCARLET). The method determines the precise location of the m(6)A
      residue and its modification fraction, which are crucial parameters in probing
      the cellular dynamics of m(6)A modification. We applied the method to determine
      the m(6)A status at several sites in two human lncRNAs and three human mRNAs and
      found that m(6)A fraction varies between 6% and 80% among these sites. We also
      found that many m(6)A candidate sites in these RNAs are however not modified. The
      precise determination of m(6)A status in a long noncoding RNA also enables the
      identification of an m(6)A-containing RNA structural motif. 

PMID- 24141619
TI  - Safer one-pot synthesis of the 'SHAPE' reagent 1-methyl-7-nitroisatoic anhydride
      (1m7).
AB  - Estimating the reactivity of 2'-hydroxyl groups along an RNA chain of interest
      aids in the modeling of the folded RNA structure; flexible loops tend to be
      reactive, whereas duplex regions are generally not. Among the most useful
      reagents for probing 2'-hydroxyl reactivity is 1-methyl-7-nitroisatoic anhydride
      (1m7), but the absence of a reliable, inexpensive source has prevented widespread
      adoption. An existing protocol for the conversion of an inexpensive precursor 4
      nitroisatoic anhydride (4NIA) recommends the use of NaH in dimethylformamide
      (DMF), a reagent combination that most molecular biology labs are not equipped to
      handle, and that does not scale safely in any case. Here we describe a safer, one
      pot method for bulk conversion of 4NIA to 1m7 that reduces costs and bypasses the
      use of NaH. We show that 1m7 produced by this method is free of side products and
      can be used to probe RNA structure in vitro. 

PMID- 24141620
TI  - Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7
      miRNAs.
AB  - The mechanisms of gene expression regulation by miRNAs have been extensively
      studied. However, the regulation of miRNA function and decay has long remained
      enigmatic. Only recently, 3' uridylation via LIN28A-TUT4/7 has been recognized as
      an essential component controlling the biogenesis of let-7 miRNAs in stem cells.
      Although uridylation has been generally implicated in miRNA degradation, the
      nuclease responsible has remained unknown. Here, we identify the Perlman syndrome
      associated protein DIS3L2 as an oligo(U)-binding and processing exoribonuclease
      that specifically targets uridylated pre-let-7 in vivo. This study establishes
      DIS3L2 as the missing component of the LIN28-TUT4/7-DIS3L2 pathway required for
      the repression of let-7 in pluripotent cells. 

PMID- 24141621
TI  - Temporal dynamics of airborne fungi in Havana (Cuba) during dry and rainy
      seasons: influence of meteorological parameters.
AB  - The aim of this paper was to determine for first time the influence of the main
      meteorological parameters on the atmospheric fungal spore concentration in Havana
      (Cuba). This city is characterized by a subtropical climate with two different
      marked annual rainfall seasons during the year: a "dry season" and a "rainy
      season". A nonviable volumetric methodology (Lanzoni VPPS-2000 sampler) was used
      to sample airborne spores. The total number of spores counted during the 2 years
      of study was 293,594, belonging to 30 different genera and five spore types.
      Relative humidity was the meteorological parameter most influencing the
      atmospheric concentration of the spores, mainly during the rainy season of the
      year. Winds coming from the SW direction also increased the spore concentration
      in the air. In terms of spore intradiurnal variation we found three different
      patterns: morning maximum values for Cladosporium, night peaks for Coprinus and
      Leptosphaeria, and uniform behavior throughout the whole day for
      Aspergillus/Penicillium."

PMID- 24141622
TI  - Synergistic apoptotic response between valproic acid and fludarabine in chronic
      lymphocytic leukaemia (CLL) cells involves the lysosomal protease cathepsin B.
AB  - Fludarabine, a nucleoside analogue, is commonly used in combination with other
      agents for the treatment of chronic lymphocytic leukaemia (CLL). In previous
      studies, valproic acid (VPA), an inhibitor of histone deacetylases, combined with
      fludarabine to synergistically increase apoptotic cell death in CLL cells. In the
      present study, we found that the combination of fludarabine and VPA decreases the
      level of the anti-apoptotic proteins Mcl-1 and XIAP in primary CLL cells.
      Treatment with fludarabine alone, or in combination with VPA, led to the loss of
      lysosome integrity, and chemical inhibition of the lysosomal protease cathepsin
      B, using CA074-Me, was sufficient to reduce apoptosis. VPA treatment increased
      cathepsin B levels and activities in primary CLL cells, thereby priming CLL cells
      for lysosome-mediated cell death. Six previously treated patients with relapsed
      CLL were treated with VPA, followed by VPA/fludarabine combination. The combined
      therapy resulted in reduced lymphocyte count in five out of six and reduced lymph
      node sizes in four out of six patients. In vivo VPA treatment increased histone-3
      acetylation and cathepsin B expression levels. Thus, the synergistic apoptotic
      response with VPA and fludarabine in CLL is mediated by cathepsin B activation
      leading to a decrease in the anti-apoptotic proteins. 

PMID- 24141623
TI  - The residual tumor autophagy marker LC3B serves as a prognostic marker in local
      advanced breast cancer after neoadjuvant chemotherapy.
AB  - PURPOSE: This study sought to investigate the prognostic value of the autophagy
      marker microtubule-associated protein chain 3B (LC3B) in patients with residual
      tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer
      (LABC). PATIENTS AND METHODS: The expression of LC3B in residual breast cancer
      cells was assessed by immunohistochemistry in surgical specimens from 229
      patients diagnosed with histologically proven invasive breast cancer. All
      patients underwent NCT followed by mastectomy and were considered nonpathologic
      complete responders (non-pCR) after a pathologic evaluation. The prognostic value
      of various clinicopathologic factors was evaluated. RESULTS: The LC3B density was
      similar between the peripheral and central area of the tumors (P = 0.328) but was
      significantly lower in the extratumoral area (P < 0.001 and P < 0.001,
      respectively). Furthermore, LC3B density, which correlated with Beclin-1
      expression, Ki-67 index, and breast cancer subtype, served as an independent
      prognostic factor for both relapse-free survival (RFS; P = 0.012) and overall
      survival (OS; P = 0.008); the prognostic value of LC3B was most significant in
      triple-negative patients. Using a combination of LC3B expression and the status
      of residual involved lymph nodes, the patients were classified into four groups
      with different risks of relapse and death (P < 0.001 for RFS and P = 0.003 for
      OS). CONCLUSION: LC3B can be used as a prognostic marker in patients with non-pCR
      after NCT for breast cancer, which highlights the importance of autophagy in the
      biologic behavior of chemoresistant cancer cells. Furthermore, evaluating and
      targeting autophagy in the neoadjuvant setting may help prevent disease relapse
      in patients with non-pCR.

PMID- 24141624
TI  - Evaluation and clinical analyses of downstream targets of the Akt inhibitor GDC
      0068.
AB  - PURPOSE: The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target
      in cancer. However, it is unknown whether the pathway blockade required for tumor
      growth inhibition is clinically achievable. Therefore, we conducted
      pharmacodynamic studies with GDC-0068, an ATP competitive, selective Akt1/2/3
      inhibitor, in preclinical models and in patients treated with this compound.
      EXPERIMENTAL DESIGN: We used a reverse phase protein array (RPPA) platform to
      identify a biomarker set indicative of Akt inhibition in cell lines and human
      tumor xenografts, and correlated the degree of pathway inhibition with antitumor
      activity. Akt pathway activity was measured using this biomarker set in pre- and
      post-dose tumor biopsies from patients treated with GDC-0068 in the dose
      escalation clinical trial. RESULTS: The set of biomarkers of Akt inhibition is
      composed of 10 phosphoproteins, including Akt and PRAS40, and is modulated in a
      dose-dependent fashion, both in vitro and in vivo. In human-tumor xenografts,
      this dose dependency significantly correlated with tumor growth inhibition. Tumor
      biopsies from patients treated with GDC-0068 at clinically achievable doses
      attained a degree of biomarker inhibition that correlated with tumor growth
      inhibition in preclinical models. In these clinical samples, compensatory
      feedback activation of ERK and HER3 was observed, consistent with preclinical
      observations. CONCLUSION: This study identified a set of biomarkers of Akt
      inhibition that can be used in the clinical setting to assess target engagement.
      Here, it was used to show that robust Akt inhibition in tumors from patients
      treated with GDC-0068 is achievable, supporting the clinical development of this
      compound in defined patient populations.

PMID- 24141625
TI  - Reprogramming metabolism with metformin improves tumor oxygenation and
      radiotherapy response.
AB  - PURPOSE: Tumor hypoxia is a negative prognostic factor in multiple cancers, due
      in part to its role in causing resistance to radiotherapy. Hypoxia arises in
      tumor regions distal to blood vessels as oxygen is consumed by more proximal
      tumor cells. Reducing the rate of oxygen consumption is therefore a potential
      strategy to reduce tumor hypoxia. We hypothesized that the anti-diabetic drug
      metformin, which reduces oxygen consumption through inhibition of mitochondrial
      complex I, would improve radiation response by increasing tumor oxygenation.
      EXPERIMENTAL DESIGN: Tumor hypoxia was measured in xenografts before and after
      metformin treatment using 2-nitroimidazole hypoxia markers quantified by
      immunohistochemistry (IHC), flow cytometry, and positron emission tomography
      (PET) imaging. Radiation response was determined by tumor growth delay and
      clonogenic survival in xenografts with and without administration of metformin.
      The impact of metformin use on outcome was assessed in 504 patients with
      localized prostate cancer treated with curative-intent, image-guided radiotherapy
      (IGRT) from 1996 to 2012. Three-year biochemical relapse-free rates were assessed
      using the Kaplan-Meier method. RESULTS: Metformin treatment significantly
      improved tumor oxygenation in two xenograft models as measured by IHC, flow
      cytometry, and PET imaging. Metformin also led to improved radiotherapy responses
      when mice were administered metformin immediately before irradiation. Clinically,
      metformin use was associated with an independent and significant decrease in
      early biochemical relapse rates (P = 0.0106). CONCLUSION: Our data demonstrate
      that metformin can improve tumor oxygenation and response to radiotherapy. Our
      study suggests that metformin may represent an effective and inexpensive means to
      improve radiotherapy outcome with an optimal therapeutic ratio.

PMID- 24141627
TI  - Use of the proton pump inhibitor pantoprazole to modify the distribution and
      activity of doxorubicin: a potential strategy to improve the therapy of solid
      tumors.
AB  - PURPOSE: Limited drug distribution within solid tumors is an important cause of
      drug resistance. Basic drugs (e.g., doxorubicin) may be sequestered in acidic
      organelles, thereby limiting drug distribution to distal cells and diverting
      drugs from their target DNA. Here we investigate the effects of pantoprazole, a
      proton pump inhibitor, on doxorubicin uptake, and doxorubicin distribution and
      activity using in vitro and murine models. EXPERIMENTAL DESIGN: Murine EMT-6 and
      human MCF-7 cells were treated with pantoprazole to evaluate changes in endosomal
      pH using fluorescence spectroscopy, and uptake of doxorubicin using flow
      cytometry. Effects of pantoprazole on tissue penetration of doxorubicin were
      evaluated in multilayered cell cultures (MCC), and in solid tumors using
      immunohistochemistry. Effects of pantoprazole to influence tumor growth delay and
      toxicity because of doxorubicin were evaluated in mice. RESULTS: Pantoprazole
      (>200 MUmol/L) increased endosomal pH in cells, and also increased nuclear uptake
      of doxorubicin. Pretreatment with pantoprazole increased tissue penetration of
      doxorubicin in MCCs. Pantoprazole improved doxorubicin distribution from blood
      vessels in solid tumors. Pantoprazole given before doxorubicin led to increased
      growth delay when given as single or multiple doses to mice bearing MCF7
      xenografts. CONCLUSIONS: Use of pantoprazole to enhance the distribution and
      cytotoxicity of anticancer drugs in solid tumors might be a novel treatment
      strategy to improve their therapeutic index.

PMID- 24141626
TI  - Prognostic significance of pretreatment serum cytokines in classical Hodgkin
      lymphoma.
AB  - PURPOSE: Although the International Prognostic Score (IPS) is the gold standard
      for risk-stratifying patients with classical Hodgkin lymphoma (cHL), these
      criteria do not accurately predict outcome. As cytokines are critically involved
      in driving cHL, we tested whether pretreatment serum cytokine levels could
      provide additional prognostic information. EXPERIMENTAL DESIGN: Thirty cytokines
      were measured in pretreatment serum from 140 patients with cHL and compared with
      50 nonlymphoma controls. Patients were followed for event-free survival (EFS) and
      overall survival (OS), and Cox proportional hazards regression models were used
      to assess the association of individual cytokines and the cytokine profiles with
      outcome via unadjusted and IPS-adjusted HR. RESULTS: Twelve cytokines (EGF, bFGF,
      G-CSF, HGF, IL-6, IL-8, IL-12, IL-2R, IP-10, MIG, TNF-alpha, and VEGF) were
      significantly (P < 0.05) higher in patients with cHL than controls; elevated
      levels of HGF, IL-6, IL-2R, IP-10, and MIG were all associated with poorer EFS.
      Only interleukin-2 receptor (IL-2R; P = 0.002) and interleukin (IL)-6 (P < 0.001)
      were independently prognostic. Patients with increased IL-6 and IL-2R had a
      significantly higher risk of early relapse and death, a finding that remained
      significant even after IPS-based risk stratification. Although elevated IL-6 and
      IL-2R correlated with the IPS, soluble CD30 (sCD30), and thymus and activation
      related chemokine (TARC) levels, the two-cytokine model remained independently
      predictive of prognosis. CONCLUSIONS: Elevated pretreatment serum cytokines are
      associated with increased disease relapse and inferior survival in cHL. Thus, the
      pretreatment cytokine profile, particularly serum levels of IL-6 and IL-2R, may
      be used to identify patients with cHL at high risk for early-disease relapse.

PMID- 24141628
TI  - Enzalutamide for treatment of patients with metastatic castration-resistant
      prostate cancer who have previously received docetaxel: U.S. Food and Drug
      Administration drug approval summary.
AB  - This article summarizes the regulatory evaluation that led to the full approval
      of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug
      Administration (FDA) on August 31, 2012, for the treatment of patients with
      metastatic castration-resistant prostate cancer who have previously received
      docetaxel. This approval was based on the results of a randomized, placebo
      controlled trial which randomly allocated 1,199 patients with mCRPC who had
      received prior docetaxel to receive either enzalutamide, 160 mg orally once daily
      (n = 800), or placebo (n = 399). All patients were required to continue androgen
      deprivation therapy. The primary endpoint was overall survival. At the
      prespecified interim analysis, a statistically significant improvement in overall
      survival was demonstrated for the enzalutamide arm compared with the placebo arm
      [HR = 0.63; 95% confidence interval: 0.53-0.75; P < 0.0001]. The median overall
      survival durations were 18.4 months and 13.6 months in the enzalutamide and
      placebo arms, respectively. The most common adverse reactions (>=10%) included
      asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral
      edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures
      occurred in 0.9% of patients on enzalutamide compared with no patients on the
      placebo arm. Overall, the FDA's review and analyses of the submitted data
      confirmed that enzalutamide had a favorable benefit-risk profile in the study
      patient population, thus supporting its use for the approved indication. The
      recommended dose is 160 mg of enzalutamide administered orally once daily.
      Enzalutamide represents the third product that the FDA has approved in the same
      disease setting within a period of 2 years. Clin Cancer Res; 19(22); 6067-73.
      (c)2013 AACR. 

PMID- 24141629
TI  - The histone deacetylase inhibitor abexinostat induces cancer stem cells
      differentiation in breast cancer with low Xist expression.
AB  - PURPOSE: Cancer stem cells (CSC) are the tumorigenic cell population that has
      been shown to sustain tumor growth and to resist conventional therapies. The
      purpose of this study was to evaluate the potential of histone deacetylase
      inhibitors (HDACi) as anti-CSC therapies. EXPERIMENTAL DESIGN: We evaluated the
      effect of the HDACi compound abexinostat on CSCs from 16 breast cancer cell lines
      (BCL) using ALDEFLUOR assay and tumorsphere formation. We performed gene
      expression profiling to identify biomarkers predicting drug response to
      abexinostat. Then, we used patient-derived xenograft (PDX) to confirm, in vivo,
      abexinostat treatment effect on breast CSCs according to the identified
      biomarkers. RESULTS: We identified two drug-response profiles to abexinostat in
      BCLs. Abexinostat induced CSC differentiation in low-dose sensitive BCLs, whereas
      it did not have any effect on the CSC population from high-dose sensitive BCLs.
      Using gene expression profiling, we identified the long noncoding RNA Xist (X
      inactive specific transcript) as a biomarker predicting BCL response to HDACi. We
      validated that low Xist expression predicts drug response in PDXs associated with
      a significant reduction of the breast CSC population. CONCLUSIONS: Our study
      opens promising perspectives for the use of HDACi as a differentiation therapy
      targeting the breast CSCs and identified a biomarker to select patients with
      breast cancer susceptible to responding to this treatment.

PMID- 24141630
TI  - Density functional theoretical study on the preferential selectivity of
      macrocyclic dicyclohexano-18-crown-6 for Sr+2 ion over Th+4 ion during extraction
      from an aqueous phase to organic phases with different dielectric constants.
AB  - The preferential selectivity of dicyclohexano-18-crown-6 (DCH18C6) for bivalent
      Sr(+2) ion over tetravalent Th(+4) ion was investigated using generalized
      gradient approximated (GGA) BP86 and the hybrid B3LYP density functional,
      employing split valence plus polarization (SV(P)) and triple-zeta valence plus
      polarization (TZVP) basis sets in conjunction with the COSMO (conductor-like
      screening model) solvation approach. The calculated theoretical selectivity of
      DCH18C6 for Sr(+2) ion over Th(+4) ion was found to be in accord with the
      selectivity for Sr(+2) ion over Th(+4) ion observed when performing liquid-liquid
      extraction experiments in different organic solvents. While 1:1(M:L)
      stoichiometric complexation reactions can be used to predict the preferential
      selectivity of Sr(2+) ion over Th(4+) ion, the results obtained are not
      consistent with the experimental results observed upon increasing the dielectric
      constant of the solvent. The calculated theoretical gas-phase data for the free
      energy of complexation, ?G, fail to explain the selectivity for Sr(+2) ion over
      Th(+4) ion. However, when 1:2 (M:L) stoichiometric complexation reactions
      (reported in previous X-ray crystallography studies) are considered, correct and
      consistent results for the selectivity for Sr(+2) ion over a wide range of
      dielectric constants are predicted. The distribution constant for Sr(2+) and
      Th(4+) ions was found to gradually increase with increasing dielectric constant
      of the organic solvent, and was found to be highest in nitrobenzene. The
      selectivity data calculated from ??G ext are in excellent agreement with the
      results obtained from solvent extraction experiments. 

PMID- 24141631
TI  - An in vitro assessment of the cerebral hemodynamics through three patient
      specific circle of Willis geometries.
AB  - The Circle of Willis (CoW) is a complex pentagonal network comprised of fourteen
      cerebral vessels located at the base of the brain. The collateral flow feature
      within the circle of Willis allows the ability to maintain cerebral perfusion of
      the brain. Unfortunately, this collateral flow feature can create undesirable
      flow impact locations due to anatomical variations within the CoW. The
      interaction between hemodynamic forces and the arterial wall are believed to be
      involved in the formation of cerebral aneurysms, especially at irregular
      geometries such as tortuous segments, bends, and bifurcations. The highest
      propensity of aneurysm formation is known to form at the anterior communicating
      artery (AcoA) and at the junctions of the internal carotid and posterior
      communicating arteries (PcoAs). Controversy still remains as to the existence of
      blood flow paths through the communicating arteries for a normal CoW. This paper
      experimentally describes the hemodynamic conditions through three thin walled
      patient specific models of a complete CoW based on medical images. These models
      were manufactured by a horizontal dip spin coating method and positioned within a
      custom made cerebral testing system that simulated symmetrical physiological
      afferent flow conditions through the internal carotid and vertebral arteries. The
      dip spin coating procedure produced excellent dimensional accuracy. There was an
      average of less than 4% variation in diameters and wall thicknesses throughout
      all manufactured CoW models. Our cerebral test facility demonstrated excellent
      cycle to cycle repeatability, with variations of less than 2% and 1% for the time
      and cycle averaged flow rates, respectively. The peak systolic flow rates had
      less than a 4% variation. Our flow visualizations showed four independent flow
      sources originating from all four inlet arteries impacting at and crossing the
      AcoA with bidirectional cross flows. The flow paths entering the left and right
      vertebral arteries dissipated throughout the CoW vasculature from the posterior
      to anterior sides, exiting through all efferent vessels. Two of the models had
      five flow impact locations, while the third model had an additional two impact
      locations within the posterior circulation caused by an additional bidirectional
      cross flows along the PcoAs during the accelerating and part of the decelerating
      phases. For a complete CoW, bidirectional cross flows exist within the AcoA and
      geometrical variations within the CoW geometry can either promote uni- or
      bidirectional cross flows along the PcoAs.

PMID- 24141632
TI  - Astigmatism impact on visual performance: meridional and adaptational effects.
AB  - PURPOSE: Astigmatic subjects are adapted to their astigmatism and perceptually
      recalibrate upon its correction. However, the extent to which prior adaptation to
      astigmatism affects visual performance, whether this effect is axis dependent,
      and the time scale of potential changes in visual performance after astigmatism
      correction are not known. Moreover, the effect of possible positive interactions
      of aberrations (astigmatism and coma) might be altered after recalibration to
      correction of astigmatism. METHODS: Visual acuity (VA) was measured in 25
      subjects (astigmats and non-astigmats, corrected and uncorrected) under induction
      of astigmatism and combinations of astigmatism and coma while controlling subject
      aberrations. Astigmatism (1.00 diopter) was induced at three different
      orientations, the natural axis, the perpendicular orientation, and 45 degrees for
      astigmats and at 0, 90, and 45 degrees for non-astigmats. Experiments were also
      performed, adding coma (0.41 MUm at a relative angle of 45 degrees) to the same
      mentioned astigmatism. Fourteen different conditions were measured using an 8
      Alternative Forced Choice procedure with Tumbling E letters and a QUEST
      algorithm. Longitudinal measurements were performed up to 6 months. Uncorrected
      astigmats were provided with proper astigmatic correction after the first
      session. RESULTS: In non-astigmats, inducing astigmatism at 90 degrees, produced
      a statistically lower reduction in VA than at 0 or 45 degrees, whereas in
      astigmats, the lower decrease in VA occurred for astigmatism induced at the
      natural axis. Six months of astigmatic correction did not reduce the
      insensitivity to astigmatic induction along the natural axis. Differences after
      orientation of astigmatism were also found when adding coma to astigmatism.
      CONCLUSIONS: The impact of astigmatism on VA is greatly dependent on the
      orientation of the induced astigmatism, even in non-astigmats. Previous
      experience to astigmatism plays a significant role on VA, with a strong bias
      toward the natural axis. In contrast to perceived isotropy, the correction of
      astigmatism does not shift the bias in VA from the natural axis of astigmatism.

PMID- 24141633
TI  - Repeatability of OCT lens thickness measures with age and accommodation.
AB  - PURPOSE: To investigate crystalline lens thickness (LT) across a range of ages
      and accommodative demands and to evaluate the repeatability of LT measurements
      using the Visante Anterior Segment Optical Coherence Tomographer (AS-OCT) (Zeiss
      Meditec, Germany) under non-cycloplegic conditions. METHODS: Participants were 98
      visually normal adults aged 18-75 years, stratified into age groups of 18-29, 30
      39, 40-49, 50-59, and 60-75 years of age. Images of the crystalline lens were
      taken using the Visante AS-OCT during stimulation of accommodation at demands of
      0, 1, 2, 3, 4, 5, and 8 D with accommodative response measured in a subgroup of
      participants. Images were analyzed and LT measured assuming a refractive index of
      1.42. Repeat measures were taken from 86 participants for each accommodative
      demand at a second visit. RESULTS: The mean unaccommodated LT for all
      participants was 4.07 +/- 0.40 mm. An average increase in LT of 20 MUm per year
      was calculated (linear regression, R2 = 0.61, F(1,89) = 143.92, p < 0.00001).
      Increase in LT with accommodation was shown to be significant in the 18- to 29
      year-olds (repeated measures ANOVA, F(6,105) = 96.31, p < 0.00001), 30- to 39
      year-olds (F(6,93) = 71.25, p < 0.00001), and 40- to 49-year-olds (F(6,90) =
      12.60, p < 0.01) with little or no measureable change in the older age groups.
      Eighty-six participants returned for a second visit. The mean difference in LT in
      the unaccommodated state for all participants between visit 1 and visit 2 was
      0.0006 mm (95% limits of agreement of -0.07 to 0.07 mm). The 95% limits of
      agreement were widest for youngest age groups and narrowest for the oldest
      participants. CONCLUSIONS: This study is the first to report the repeatability of
      LT measures using the Visante AS-OCT in the non-cyclopleged eye. It has also
      demonstrated the ability of the Visante AS-OCT to detect small changes in lens
      thickness with accommodation.

PMID- 24141634
TI  - Consequences of wear interruption for discomfort with contact lenses.
AB  - PURPOSE: To establish whether increased end-of-day discomfort during soft contact
      lens wear is associated with short-term changes occurring to the lens itself.
      METHODS: Twenty-seven subjects wore hydrogel lenses (Focus Dailies; Alcon)
      bilaterally for 10 hours on two separate days. Comfort was reported using 1-100
      numerical rating scales (1 = intolerable discomfort, 100 = lens cannot be felt).
      Day 1 ratings were taken before lens insertion and at 0.05, 5, and 10 hours post
      insertion. Day 2 ratings occurred at similar times, but lenses were removed after
      the 5-hour assessment and either reinserted (n = 14) or newly replaced (n = 12).
      An additional rating was taken 5 minutes after re-insertion. Wear then continued
      to the 10-hour point. In a separate study, 24 different subjects repeated these
      procedures using a silicone hydrogel lens (AirOptix Aqua; Alcon) with wear taking
      place on 3 days to permit lens replacement to be with existing as well as new
      lenses in all subjects. RESULTS: For hydrogel lenses, comfort scores (mean +/-
      95% CI) reported after 10 hours were 79.4 +/- 8.3 when lenses were worn un
      replaced, compared with 73.2 +/- 9.2 for replacement with the existing lens. When
      replacement was with a brand new lens, the corresponding values were 72.9 +/-
      10.9 (un-replaced) versus 69.2 +/- 12.8 (new lens replacement). For silicone
      hydrogel lenses, 10-hour comfort was 90.3 +/- 3.2 (un-replaced) versus 92.2 +/-
      2.9 (replacement with existing lens) versus 90.0 +/- 3.3 (replacement with new
      lens). Differences between replacement conditions were not significant in any
      case (analysis of variance, p > 0.05). CONCLUSIONS: Final comfort was not
      influenced by replacing lenses midway through the wearing period. Comfort
      decrements experienced by users of these daily contact lenses towards the later
      part of the wearing period are not caused by changes occurring to the lenses on
      this time scale. Possible alternative etiological factors include a fatigue-like
      response in one or more ocular tissues or stimulation of ocular surface
      nociceptors induced by the presence of the contact lens.

PMID- 24141635
TI  - Sunglasses with thick temples and frame constrict temporal visual field.
AB  - PURPOSE: Our aim was to compare the impact of two types of sunglasses on visual
      field and glare: one ("thick sunglasses") with a thick plastic frame and wide
      temples and one ("thin sunglasses") with a thin metal frame and thin temples.
      METHODS: Using the Goldmann perimeter, visual field surface areas (cm2) were
      calculated as projections on a 30-cm virtual cupola. A V4 test object was used,
      from seen to unseen, in 15 healthy volunteers in the primary position of gaze
      ("base visual field"), then allowing eye motion ("eye motion visual field")
      without glasses, then with "thin sunglasses," followed by "thick sunglasses."
      Visual field surface area differences greater than the 14% reproducibility error
      of the method and having a p < 0.05 were considered significant. A glare test was
      done using a surgical lighting system pointed at the eye(s) at different
      incidence angles. RESULTS: No significant "base visual field" or "eye motion
      visual field" surface area variations were noted when comparing tests done
      without glasses and with the "thin sunglasses." In contrast, a 22% "eye motion
      visual field" surface area decrease (p < 0.001) was noted when comparing tests
      done without glasses and with "thick sunglasses." This decrease was most severe
      in the temporal quadrant (-33%; p < 0.001). All subjects reported less lateral
      glare with the "thick sunglasses" than with the "thin sunglasses" (p < 0.001).
      CONCLUSIONS: The better protection from lateral glare offered by "thick
      sunglasses" is offset by the much poorer ability to use lateral space
      exploration; this results in a loss of most, if not all, of the additional visual
      field gained through eye motion.

PMID- 24141636
TI  - Combined angiography for high-quality near-infrared autofluorescence images.
AB  - PURPOSE: To describe an innovative imaging technique to obtain high-quality near
      infrared autofluorescence (NIA) images. METHODS: Simultaneous fluorescein
      angiography + indocyanine green angiography (FA + ICGA) acquisition mode (without
      dye injection) of Spectralis HRA + OCT (Heidelberg Retina Angiograph; Heidelberg
      Engineering, Heidelberg, Germany), setting maximum level of illuminance, and
      Automatic Real-time (ART) Module (Heidelberg Engineering) to increase signal-to
      noise ratio. RESULTS: The combined confocal scanning laser ophthalmoscope
      technique allows the Spectralis HRA + OCT device to create high-quality NIA ART
      images. CONCLUSIONS: This innovative imaging technique, consisting of
      simultaneous FA + ICGA acquisition mode, setting maximum level of illuminance,
      and ART, allows the Spectralis HRA + OCT device to create high-quality NIA ART
      images, without requiring the need for the HRA2 (Heidelberg Retina Angiograph;
      Heidelberg Engineering) device.

PMID- 24141637
TI  - Bacterial genetics: defeating the drawbacks of CRISPR.

PMID- 24141638
TI  - Bacterial evolution: getting to the bottom of Cyanobacteria.

PMID- 24141639
TI  - Gene expression analysis in the roots of salt-stressed wheat and the cytogenetic
      derivatives of wheat combined with the salt-tolerant wheatgrass, Lophopyrum
      elongatum.
AB  - KEY MESSAGE: Using microarray analysis, we identified regulatory and signaling
      related genes with differential expression in three genotypes with varying
      degrees of salt tolerance, Triticum aestivum , the amphiploid, and the wheat
      substitution line DS3E(3A). Lophopyrum elongatum is among one of the most salt
      tolerant members of the Triticeae; important genetic stocks developed from
      crosses between wheat and L. elongatum provide a unique opportunity to compare
      gene expression in response to salt stress between these highly related species.
      The octaploid amphiploid contains the entire genome of T. aestivum and L.
      elongatum, and the disomic substitution line DS3E(3A) has chromosome 3A of wheat
      replaced by chromosome 3E of L. elongatum. In this study, microarray analysis was
      used to characterize gene expression profiles in the roots of three genotypes,
      Triticum aestivum, the octaploid amphiploid, and the wheat DS3E(3A) substitution
      line, in response to salt stress. We first examined changes in gene expression in
      wheat over a time course of 3 days of salt stress, and then compared changes in
      gene expression in wheat, the T. aestivum * L. elongatum amphiploid, and in the
      DS3E(3A) substitution line after 3 days of salt stress. In the time course
      experiment, 237 genes had 1.5 fold or greater change at least one out of three
      time points assayed in the experiment. The comparison between the three genotypes
      revealed 304 genes with significant differences in changes of expression between
      the genotypes. Forty-two of these genes had at least a twofold change in
      expression in response to salt treatment; 18 of these genes have signaling or
      regulatory function. Genes with significant differences in induction or
      repression between genotypes included transcription factors, protein kinases,
      ubiquitin ligases and genes related to phospholipid signaling.

PMID- 24141640
TI  - Differential white cell count and incident type 2 diabetes: the Insulin
      Resistance Atherosclerosis Study.
AB  - AIMS/HYPOTHESIS: White cell count has been shown to predict incident type 2
      diabetes, but differential white cell count has received scant attention. We
      examined the risk of developing diabetes associated with differential white cell
      count and neutrophil:lymphocyte ratio and the effect of insulin sensitivity and
      subclinical inflammation on white cell associations. METHODS: Incident diabetes
      was ascertained in 866 participants aged 40-69 years in the Insulin Resistance
      Atherosclerosis Study after a 5 year follow-up period. The insulin sensitivity
      index (SI) was measured by the frequently sampled IVGTT. RESULTS: C-reactive
      protein was directly and independently associated with neutrophil (p < 0.001) and
      monocyte counts (p < 0.01) and neutrophil:lymphocyte ratio (p < 0.001), whereas
      SI was inversely and independently related to lymphocyte count (p < 0.05). There
      were 138 (15.9%) incident cases of diabetes. Demographically adjusted ORs for
      incident diabetes, comparing the top and bottom tertiles of white cell (1.80 [95%
      CI 1.10, 2.92]), neutrophil (1.67 [1.04, 2.71]) and lymphocyte counts (2.30
      [1.41, 3.76]), were statistically significant. No association was demonstrated
      for monocyte count (1.18 [0.73, 1.90]) or neutrophil:lymphocyte ratio (0.89
      [0.55, 1.45]). White cell and neutrophil associations were no longer significant
      after further adjusting for family history of diabetes, fasting glucose and
      smoking, but the OR comparing the top and bottom tertiles of lymphocyte count
      remained significant (1.96 [1.13, 3.37]). This last relationship was better
      explained by SI rather than C-reactive protein. CONCLUSIONS/INTERPRETATION: A
      lymphocyte association with incident diabetes, which was the strongest
      association among the major white cell types, was partially explained by insulin
      sensitivity rather than subclinical inflammation.

PMID- 24141641
TI  - "You get caught up": youth decision-making and violence.
AB  - Violence is a major cause of morbidity and mortality among adolescents. We
      conducted serial focus groups with 30 youth from a violence prevention program to
      discuss violence in their community. We identified four recurrent themes
      characterizing participant experiences regarding peer decision-making related to
      violence: (1) youth pursue respect, among other typical tasks of adolescence; (2)
      youth pursue respect as a means to achieve personal safety; (3) youth recognize
      pervasive risks to their safety, frequently focusing on the prevalence of
      firearms; and (4) as youth balance achieving respect in an unsafe setting with
      limited opportunities, they express conflict and frustration. Participants
      recognize that peers achieve peer-group respect through involvement in unsafe or
      unhealthy behavior including violence; however they perceive limited alternative
      opportunities to gain respect. These findings suggest that even very high risk
      youth may elect safe and healthy alternatives to violence if these opportunities
      are associated with respect and other adolescent tasks of development. 

PMID- 24141642
TI  - Intraspecific rearrangement of duplicated mitochondrial control regions in the
      Luzon Tarictic Hornbill Penelopides manillae (Aves: Bucerotidae).
AB  - Philippine hornbills of the genera Aceros and Penelopides (Bucerotidae) are known
      to possess a large tandemly duplicated fragment in their mitochondrial genome,
      whose paralogous parts largely evolve in concert. In the present study, we
      surveyed the two distinguishable duplicated control regions in several
      individuals of the Luzon Tarictic Hornbill Penelopides manillae, compare their
      characteristics within and across individuals, and report on an intraspecific
      mitochondrial gene rearrangement found in one single specimen, i.e., an
      interchange between the two control regions. To our knowledge, this is the first
      observation of two distinct mitochondrial genome rearrangements within a bird
      species. We briefly discuss a possible evolutionary mechanism responsible for
      this pattern, and highlight potential implications for the application of control
      region sequences as a marker in population genetics and phylogeography. 

PMID- 24141643
TI  - Size, separation, structural order, and mass density of molecules packing in
      water and ice.
AB  - The structural symmetry and molecular separation in water and ice remain
      uncertain. We present herewith a solution to unifying the density, the structure
      order and symmetry, the size (H-O length dH), and the separation (d(OO) = d(L) +
      d(H) or the O:H length d(L)) of molecules packing in water and ice in terms of
      statistic mean. This solution reconciles: i) the d(L) and the d(H) symmetrization
      of the O:H-O bond in compressed ice, ii) the d(OO) relaxation of cooling water
      and ice and, iii) the d(OO) expansion of a dimer and between molecules at water
      surface. With any one of the d(OO), the density rho(g.cm-3), the d(L), and the
      d(H), as a known input, one can resolve the rest quantities using this solution
      that is probing conditions or methods independent. We clarified that: i) liquid
      water prefers statistically the mono-phase of tetrahedrally-coordinated structure
      with fluctuation, ii) the low-density phase (supersolid phase as it is strongly
      polarized with even lower density) exists only in regions consisting molecules
      with fewer than four neighbors and, iii) repulsion between electron pairs on
      adjacent oxygen atoms dictates the cooperative relaxation of the segmented O:H-O
      bond, which is responsible for the performance of water and ice.

PMID- 24141644
TI  - A multidisciplinary approach to improve preoperative understanding and reduce
      anxiety: a randomised study.
AB  - BACKGROUND: Emotional factors may influence reception of information provided
      during informed consent leading to incomplete understanding and reduced
      satisfaction. OBJECTIVE: This study was designed to test the hypothesis that a
      multidisciplinary approach could improve understanding of the information
      provided by the anaesthesiologist and in turn, reduce anxiety. DESIGN: A
      randomised controlled clinical trial. SETTING: Veneto Oncology Institute, Italian
      comprehensive cancer centre. Recruitment from December 2008 to June 2010.
      PATIENTS: Two hundred and fifty-one women requiring anaesthesia for breast cancer
      surgery. INTERVENTIONS: Women undergoing surgery for primary breast cancer were
      randomly assigned to either the structured anaesthesiology interview group (SAI)
      or the integrated multidisciplinary psycho-oncological approach (IPA). In the IPA
      arm, patients underwent an interview with the psycho-oncologist. Subsequently,
      and prior to preoperative anaesthesia evaluation, the psycho-oncologist informed
      the anaesthesiologist of the type of communicative strategy to adopt for each
      individual. In the SAI arm, patients received only the anaesthesiology interview.
      MAIN OUTCOME MEASURES: Anxiety as assessed by State-Trait Anxiety Inventory
      (STAI) questionnaire. RESULTS: Two hundred and fifty-one patients were randomised
      and 234 analysed: 124 in the IPA arm and 110 in the SAI arm. For both groups,
      mean anxiety scores, according to the STAI questionnaire, were statistically
      lower after the anaesthesiology visit than at baseline, with a reduction of 6.5
      points for the IPA arm [95% confidence interval (CI) 4.6 to 8.4, P < 0.0001] and
      4.7 points for the SAI arm (95% CI 2.6 to 6.7, P < 0.0001). There were no
      significant differences between the two groups in the mean anxiety score before
      and after the interview. For highly anxious patients, the STAI score decreased
      significantly more in the IPA group (10.2 points, 95% CI 7.4 to 13.0) than in the
      SAI group (6.8 points, 95% CI 3.8 to 9.8), P = 0.024.The information provided
      during the anaesthesiology visit was correctly understood by more than 80% of
      patients and was similar in both groups. CONCLUSION: In breast cancer surgical
      patients with high levels of preoperative anxiety, a multidisciplinary approach
      with psycho-oncological intervention proved to be useful at the preoperative
      anaesthesiology interview.

PMID- 24141645
TI  - Anaesthesia and orphan disease: failed airway management in a case of Smith
      McCort Dysplasia.

PMID- 24141646
TI  - Intravenous nonopioid analgesic drugs in chronic low back pain patients on
      chronic opioid treatment: a crossover, randomised, double-blinded, placebo
      controlled study.
AB  - BACKGROUND: Addition of nonopioid analgesic drugs reduces pain and opioid
      requirements in acute low back pain. In noncancer chronic low back pain (CLBP),
      the efficacy of a combined regimen to reduce breakthrough pain has not been
      proven so far. OBJECTIVE: Evaluation of the effects of intravenous (i.v.)
      nonopioid analgesic drugs on pain intensity and lumbar mobility in CLBP patients
      on chronic opioid therapy. DESIGN: Randomised, placebo-controlled, double
      blinded, crossover study. SETTING: Vienna General Hospital, Austria, from
      December 2002 to May 2004. PATIENTS: Thirty-six adults with CLBP on chronic
      opioid therapy. Inclusion criteria are as follows: American Society of
      Anesthesiologists' physical status less than 3, visual analogue scale (VAS) more
      than 4 and no known allergy to any of the used drugs. INTERVENTION: After written
      informed consent and VAS assessment, any oral nonopioid analgesic drug (NSAIDs,
      metamizol, paracetamol) was replaced by placebo 10 days before the first test
      infusion as a washout period. Coanalgesics (anticonvulsants, antidepressants)
      were maintained. Each patient received randomly four i.v. test infusions of
      diclofenac 75 mg (and orphenadrine 30 mg), parecoxib 40 mg, paracetamol 1 g and
      isotonic saline. A washout time of 72 h was allowed between each infusion. MAIN
      OUTCOME MEASURES: Primary outcome was as follows: VAS pain intensity (0 to 100
      mm) at inclusion, before and within 30 min after infusion. Secondary outcomes
      were as follows: Roland-Morris questionnaire, McGill pain questionnaire and a
      test panel of physical functioning for spinal mobility, muscular endurance,
      balance and coordination. The differences in means of the above assessments among
      the groups were analysed. RESULTS: We found an improvement in VAS from the day of
      inclusion to the day of each appointment. We observed no improvement in pain
      intensity (VAS) or in any of the physical functioning tests immediately before
      versus after administration of the four i.v. drugs. Reductions in sensory,
      affective and cognitive dimensions of the McGill pain questionnaire were
      statistically significant in the diclofenac group. A trend of McGill pain
      questionnaire improvement existed in the other groups. CONCLUSION: The present
      data show that the anticipation of an i.v. infusion of nonopioid analgesic drug
      improves VAS significantly, probably through expectation-related mechanisms.
      However, single dose i.v. infusions of nonopioid analgesic drugs fail to improve
      pain intensity and spinal mobility in CLBP patients on chronic opioid treatment,
      even immediately after the infusion.

PMID- 24141647
TI  - Children's agency, interests, and medical consent.
AB  - In this paper I argue that reference to a developmental account of agency can
      help explain, and in cases also alter, our current practices when it comes to the
      non-consensual medical treatment of children. It does this through its
      explanation of how stages of development impact the types of interests we have. 

PMID- 24141649
TI  - Establishment and characterization of seven human breast cancer cell lines
      including two triple-negative cell lines.
AB  - Permanently growing cell lines can be invaluable because of their usefulness in a
      variety of experimental situations. We report the characteristics of seven cell
      lines designated, SNU-306, SNU-334, SNU-1528, SNU-1553, SNU-1581, SNU-1958 and
      SNU-2372, which were established from three primary carcinomas, two pleural
      effusion, one pericardial effusion and one ascitic fluid samples obtained from
      seven Korean breast carcinoma patients. The histopathology of the primary tumors
      and their in vitro growth characteristics are described. DNA fingerprinting
      analysis and genetic alterations in the p53 and EGFR genes were conducted. The
      expression levels of the ER-alpha, PR, C-erbB2, E-cadherin, COX-2, MDR and MXR
      genes were investigated and sensitivity to anticancer drugs was screened. Growth
      was as adherent cells (four cell lines), floating aggregates (one cell line) and
      both (two cell lines). All lines were free of mycoplasma or bacteria and were
      proven unique by DNA fingerprinting analysis using 18 microsatellite markers.
      Estrogen receptor (ER) mRNA was highly expressed in five cell lines and low or
      undetectable in SNU-1958 and SNU-2372. Progesterone receptor (PR) mRNA was
      expressed only in the SNU-306. SNU-1958 and SNU-2372 were hormone receptor
      negative and C-erbB2-negative (triple-negative). SNU-1528 had an in-frame
      deletion of 42 base pairs of p53 gene and showed over 20-fold resistance for
      taxol compared to the other cell lines. There were no mutation in the EGFR gene;
      COX-2 was expressed in four cell lines and MXR was expressed in two cell lines.
      These well-characterized seven breast cancer cell lines, which include two triple
      negative cell lines, will be useful for the study of breast cancer biology. 

PMID- 24141653
TI  - On the structure of the thiolated Au15 cluster.
AB  - The structure of the Au15-thiolate cluster has been elucidated using a DFT
      approach, and it is demonstrated to comprise a Au4-tetrahedron core protected
      solely by the combination of two concatenated staple motifs. The longer motif
      efficiently wraps the core, and threads the shorter one. The structural
      assignment is supported by comparison to the powder X-ray diffraction pattern
      and, via time dependent-DFT calculations, to the optical and chiroptical (CD)
      absorption spectra. The calculated CD spectrum features a characteristic strong
      peak centered at 3.48 eV in accordance with the experimental profile. These
      results confirm the existence of long Au(I)-thiolate motifs as protecting units
      of small thiolated gold clusters with a thiolate-to-gold ratio comparable to the
      Au15(SR)13 cluster.

PMID- 24141650
TI  - Combination of a haploidentical SCT with an unrelated cord blood unit: a single
      arm prospective study.
AB  - We conducted a single-arm prospective study in 50 patients who received the
      combination of an haploidentical stem cell graft and an unrelated umbilical cord
      blood unit for the treatment of hematological malignancies. The median time for
      neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days
      (11-180 days). All surviving patients attained complete haploidentical
      engraftment except three patients who presented a mixed engraftment with
      increasing cord blood and decreasing haplo mismatch chimerism during the first 4
      months after transplantation. The cumulative incidence of grade II-IV acute GVHD
      was 20%+/-0.327% at day+100, and the incidence of chronic GVHD was 19.26%+/-1.0%
      at 1 year. The 1-year cumulative incidence of relapse was 19.78%+/-1%, and the
      TRM was 16.2%+/-0.54%. At 1 year, overall survival was 78.6%+/-7.6% and PFS
      64.0%+/-11.0%. The BU/CY-based conditional regimen showed a significant
      superiority over TBI/CY on PFS (relative risk=5.012, 95% confidence interval,
      1.146-21.927, P=0.032). In conclusion, the co-infusion of an unrelated cord blood
      unit may potentially improve the outcome of haploidentical allogeneic
      hematopoietic SCT. 

PMID- 24141651
TI  - Successful rescue of early graft failure in pediatric patients using T-cell
      depleted haploidentical hematopoietic SCT.
AB  - Graft failure (GF) is a significant complication after allogeneic hematopoietic
      stem cell transplantation (HCT) and is associated with a high mortality rate. We
      performed re-transplantation using haploidentical-related donors to rescue
      children with early GF. Between 2008 and 2013, 10 patients received re
      transplantation from haploidentical family donors. The median age at HCT was 13.5
      years and the median time between transplantations was 52.5 days. Conditioning
      regimen with fludarabine and CY was used in seven patients, and TBI was added in
      three patients. All 10 patients received T-cell-depleted grafts using CD3 or
      CD3/CD19 MoAb. The median numbers of CD34(+) and CD3(+) cells were 5.52 *
      10(6)/kg and 1.08 * 10(6)/kg, respectively. For GVHD prophylaxis, mycophenolate
      mofetil (MMF) and tacrolimus or MMF and CYA were used. All 10 patients achieved a
      sustained neutrophil engraftment and maintained a complete donor chimerism at the
      time of analysis (median 23 months, range 6-62 months). Nine of 10 patients were
      alive, and one patient with moyamoya disease with AML died of encephalopathy 7
      months post transplant. This study suggests that fludarabine- and CY-based
      conditioning with T-cell-depleted haploidentical HCT is a feasible option to
      rescue pediatric patients with primary GF. 

PMID- 24141654
TI  - Determination of umbilical venous catheter tip position with radiograph.
AB  - OBJECTIVES: To compare the cardiac silhouette method with the vertebral body
      method in predicting the umbilical venous catheter tip position on ultrasound; to
      measure the length of the target zone for the umbilical venous catheter tip; and
      to determine the time taken for a neonatologist to ascertain position of the
      umbilical venous catheter tip with ultrasound. DESIGN: Prospective cohort study.
      SETTING: Neonatal ICU. PATIENTS: Newborn infants with an umbilical venous
      catheter. INTERVENTIONS: Ultrasound scans to determine the umbilical venous
      catheter tip position were performed within an hour of corresponding
      anteroposterior chest-abdominal radiograph. MEASUREMENTS AND MAIN RESULTS: Two
      hundred paired radiograph and ultrasound scans in 82 newborn infants were
      analyzed. Each radiograph was reviewed independently by an experienced
      neonatologist who recorded the position of the umbilical venous catheter tip by
      vertebral level and by the cardiac silhouette method. For each method, the
      sensitivity, specificity, and positive and negative predictive values were
      calculated for the prediction of the true position of the catheter tip on
      ultrasound. The umbilical venous catheter tip was well positioned in just 28 of
      200 scans. The cardiac silhouette method was superior to the vertebral level
      method for all test variables, with a sensitivity and specificity of 86% and 94%
      compared with 61% and 74%. The length of the target zone approximates to a single
      T8 vertebral body height on radiograph. CONCLUSIONS: For radiograph and
      ultrasound scans performed within an hour of each other, the cardiac silhouette
      method more accurately predicts umbilical venous catheter tip than vertebral body
      level and methods described in previous studies. Catheters are frequently
      malpositioned. The length of the target zone for optimal umbilical venous
      catheter tip position is short. Ultrasound assessment of umbilical venous
      catheter tip position is quick.

PMID- 24141655
TI  - Vasopressin as a rescue therapy for refractory pulmonary hypertension in
      neonates: case series.
AB  - OBJECTIVES: To determine the effect of vasopressin therapy on the efficacy of
      oxygenation and arterial pressure in infants with severe persistent pulmonary
      hypertension of the newborn. DESIGN: Retrospective case study. SETTING: Neonatal
      ICU, Hospital for Sick Children, Toronto, Canada. SUBJECTS: Neonates with severe
      persistent pulmonary hypertension. INTERVENTION: Intravenous infusion of
      vasopressin. MEASUREMENTS AND MAIN RESULTS: Ten infants satisfied the inclusion
      criteria. Inhaled nitric oxide was used for median (interquartile range) duration
      of 15 hours (11-28 hr) prior to vasopressin commencement. Vasopressin was
      initiated at a mean dose of 0.0002 +/- 0.0002 U/kg/min for a median
      (interquartile range) duration of 49 hours (13-95 hr). Administration of
      vasopressin was associated with an improvement in oxygenation index, peak effect
      6 hours after drug initiation (p = 0.01), and a reduction in inhaled nitric oxide
      dose (p < 0.05). There was a concomitant improvement in blood pressure (p < 0.05)
      and urine output (p < 0.05), without drop in the serum sodium level or worsening
      in serum lactate level. CONCLUSIONS: Although there is limited experience of
      vasopressin use in persistent pulmonary hypertension of the newborn infants, our
      case series suggests it to be a potential adjunctive therapy for improving the
      efficacy of oxygenation and systemic hypotension. A prospective randomized trial
      is needed to confirm its efficacy and safety in the management of severe
      persistent pulmonary hypertension of the newborn.

PMID- 24141656
TI  - Incidence of catheter-related bloodstream infections in neonates following
      removal of peripherally inserted central venous catheters.
AB  - OBJECTIVES: Catheter-associated bloodstream infections are a significant source
      of morbidity and healthcare cost in the neonatal ICU. Previous studies examining
      the prevalence of bloodstream infections after removal of peripherally inserted
      central venous catheters in neonates are equivocal. DESIGN: A retrospective
      cohort study. PATIENTS: All infants with peripherally inserted central venous
      catheters treated at the Vanderbilt neonatal ICU between 2007 and 2009.
      MEASUREMENTS AND MAIN RESULTS: We evaluated the following outcomes: 1)
      bloodstream infections, 2) culture-negative sepsis, 3) number of sepsis
      evaluations, and 4) number of significant apnea/bradycardia events comparing odds
      ratios between 72 hours before and 72 hours after peripherally inserted central
      venous catheter removal. We analyzed a total of 1,002 peripherally inserted
      central venous catheters in 856 individual infants with a median (interquartile
      range) gestational age of 31 weeks (28-37 wk) and a median birth weight of 1,469
      g (960-2,690 g). Comparing 72 hours before with 72 hours after peripherally
      inserted central venous catheter removal did not show a difference in the
      prevalence of bloodstream infections (9 vs 3, p = 0.08), prevalence of culture
      negative sepsis (37 vs 40, p = 0.73), number of sepsis evaluations (p = 0.42), or
      number of apnea/bradycardia events (p = 0.32). However, in peripherally inserted
      central venous catheter not used for delivery of antibiotics, there was a 3.83
      fold increase in odds for culture-negative sepsis following peripherally inserted
      central venous catheter removal (95% confidence interval, 1.48-10.5; p = 0.001).
      For infants less than 1,500 g birth weight (very low birth weight), odds for
      culture-negative sepsis increased to 6.3-fold following removal of peripherally
      inserted central venous catheters not used for antibiotic delivery (95%
      confidence interval, 1.78-26.86; p < 0.01). CONCLUSIONS: Although these data do
      not support the routine use of antibiotics for sepsis prophylaxis prior to
      peripherally inserted central venous catheter removal, they suggests that very
      low birth weight infants not recently exposed to antibiotics are at increased
      odds for associated adverse events following discontinuation of their
      peripherally inserted central venous catheter.

PMID- 24141657
TI  - Impact of the shift to neonatal noninvasive ventilation in Poland: a population
      study.
AB  - OBJECTIVE: This study was undertaken to document the real impact of a directed
      shift in the standard of neonatal practice to a pervasive use of noninvasive
      respiratory support. DESIGN: Before-after observational study. SETTING: All 18
      neonatal ICUs in the capital region of Poland. PATIENTS: Every infant admitted to
      a neonatal ICU who received respiratory pressure support over a 7-year period of
      interest (12-month transition to the new noninvasive standard and 36 months
      before and after). INTERVENTION: Education as to the benefits of noninvasive
      respiratory support and widespread availability of Infant Flow noninvasive
      ventilation systems. MEASUREMENTS AND MAIN RESULTS: Five thousand five hundred
      fifty-one infants required respiratory support in this period. Of these, 14% were
      less than 28 weeks estimated gestational age, 33% between 28 and 32 weeks, 31%
      between 33 and 36 weeks, and 22% more than 36 weeks. The use of noninvasive
      support, as the first form of respiratory support, increased by 19% (p < 0.001).
      The use of noninvasive support, for weaning following extubation, increased by
      32% (p = 0.06). The increased use in weaning was the most pronounced in infants
      younger than or equal to 32 weeks estimated gestational age (p < 0.001). There
      were two prospective primary endpoints, mortality and bad outcome among survivors
      younger than or equal to 32 weeks estimated gestational age. Mortality decreased
      from 11% to 7%, and the difference remained statistically significant after
      controlling for baseline factors (p < 0.001). The reduced mortality was more
      apparent in infants younger than or equal to 32 weeks estimated gestational age.
      In infants younger than or equal to 32 weeks estimated gestational age, bad
      outcome in survivors (grade III bronchopulmonary dyplasia and retinopathy of
      prematurity requiring laser treatment) did not increase (p = 0.669) after
      controlling for significant baseline variables. CONCLUSIONS: We believe that the
      adoption of an approach emphasizing noninvasive ventilation in Poland resulted in
      decreased mortality without an increase in significant pulmonary or retinal
      morbidity.

PMID- 24141658
TI  - Effectiveness of a clinical pathway with methadone treatment protocol for
      treatment of neonatal abstinence syndrome following in utero drug exposure to
      substances of abuse*.
AB  - OBJECTIVE: To evaluate the effectiveness of methadone for the treatment of
      neonatal abstinence syndrome when used according to a preexisting clinical
      pathway. DESIGN: This is a 3-year retrospective study conducted at a single
      institution. In this study, neonates who received methadone for the treatment of
      neonatal abstinence syndrome according to a predefined clinical treatment pathway
      were evaluated for treatment success: defined as adherence to the methadone
      regimen with no residual signs of withdrawal. Data were collected for methadone
      dosages, Lipsitz scores, length of methadone treatment, total length of hospital
      stay, and relevant clinical data. SETTING: Level III neonatal ICU. PATIENTS:
      Newborn infants with in utero exposure to substances of abuse. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Sixty patients were included. The mean
      gestational age and birth weight were 37.07 +/- 3.05 weeks and 2.77 +/- 0.6 kg.
      All 60 patients exhibited neonatal abstinence syndrome within first 72 hours of
      life. Fifty-seven of 60 patients (95%) initiated methadone treatment according to
      protocol. There was deviation from the protocol at 48 and 72 hours of treatment
      with approximately 59% and 13% of the patients still on methadone at more than
      the prescribed amount to control neonatal abstinence syndrome. The mean +/- SD
      total methadone exposure was 1.99 +/- 1.63 mg/kg, length of treatment 11.66 +/-
      9.02 days, and total hospital length of stay 22.43 +/- 29.3 days, suggesting
      significant variability in response. No significant correlation was found between
      birth weight or gestational age and length of treatment. CONCLUSION: Clinical
      pathway for treating neonatal abstinence syndrome was closely followed at the
      initial diagnosis. The doses of methadone used in the first 24-48 hours of this
      study were insufficient for adequate symptom control. Despite a formal treatment
      protocol, there was substantial variability in total methadone exposure, length
      of treatment, and length of stay, suggesting other contributory factors for the
      observed variability.

PMID- 24141660
TI  - Extracorporeal cardiopulmonary resuscitation outcomes in term and premature
      neonates*.
AB  - OBJECTIVE: Extracorporeal cardiopulmonary resuscitation appears to improve
      survival in patients with acute refractory cardiopulmonary failure. This analysis
      was performed to determine survival outcomes and predictors of in-hospital
      mortality for term and preterm neonates who received extracorporeal
      cardiopulmonary resuscitation. DESIGN: Retrospective review of data from the
      Extracorporeal Life Support Organization international registry. SETTING:
      Pediatric and neonatal ICUs. PATIENTS: Infants less than or equal to 30 days.
      INTERVENTIONS: Extracorporeal cardiopulmonary resuscitation. MEASUREMENTS AND
      MAIN RESULTS: Demographic, clinical, and survival data from patients who received
      extracorporeal cardiopulmonary resuscitation between 1998 and 2010 were analyzed
      to determine factors that affect in-hospital mortality. Overall survival to
      hospital discharge for the 641 neonates who received extracorporeal
      cardiopulmonary resuscitation was 39%. In univariate analysis, gestational age
      correlated inversely with stroke (odds ratio, 0.84 [95% CI, 0.75-0.95]; p =
      0.006) and death (odds ratio, 0.87 [95% CI, 0.78-0.96]; p = 0.005) as did
      corrected gestational age (odds ratio, 0.89 [95% CI, 0.81-0.97]; p = 0.006) and
      birth weight (odds ratio, 0.53 [95% CI, 0.38-0.74]; p < 0.001). Dysrhythmia as
      the primary diagnosis had significantly lower odds of death than single-ventricle
      cardiac disease (odds ratio, 0.24 [95% CI, 0.06-0.95]; p = 0.04). Higher pre
      extracorporeal cardiopulmonary resuscitation oxygenation decreased the odds of
      death (odds ratio, 0.996 [95% CI, 0.994-0.999]; p = 0.01), whereas complications
      occurring on extracorporeal life support increased the odds of death. In the
      multivariate analysis, lower birth weight and pre-extracorporeal cardiopulmonary
      resuscitation oxygenation, as well as complications including CNS hemorrhage,
      pulmonary hemorrhage, acidosis, renal replacement therapy, and mechanical
      complications, increased the odds of death. CONCLUSIONS: Overall survival for
      neonates receiving extracorporeal cardiopulmonary resuscitation is similar to
      older pediatric patients but decreases with lower gestational age and weight.
      Despite this, many low-birth weight neonates survive to hospital discharge.

PMID- 24141659
TI  - The temporal kinetics of circulating angiopoietin levels in children with sepsis.
AB  - OBJECTIVE: Capillary integrity continues to challenge critical care physicians
      worldwide when treating children with sepsis. Vascular growth factors,
      specifically angiopoietin-1 and angiopoietin-2, play opposing roles in capillary
      stabilization in patients with sepsis. We aim to determine whether pediatric
      patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios
      when compared with nonseptic PICU patients over a 7-day period. DESIGN:
      Prospective observational study. Patients were classified within 24 hours of
      admission into non-systemic inflammatory response syndrome, systemic inflammatory
      response syndrome/sepsis, or severe sepsis/shock. Plasma levels of angiopoietin-1
      and angiopoietin-2 were measured via enzyme-linked immunosorbent assay. The
      angiopoietin-2/1 ratio was graphically plotted and determined whether patients
      fell into "constant" or "variable" patterns. SETTING: Tertiary care center PICU.
      PATIENTS: Critically ill pediatric patients with varying sepsis severity.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-five patients were
      enrolled (nine non-systemic inflammatory response syndrome, 19 systemic
      inflammatory response syndrome/sepsis, and 17 severe sepsis/shock). Gender, age,
      weight, comorbidities, and PICU length of stay were not significantly different
      between the groups. Admission pediatric risk stratification scores and net fluid
      ins/outs were significantly elevated in the severe sepsis/shock group when
      compared (all p < 0.05). Admission angiopoietin-2 levels and angiopoietin-2/1
      ratios were significantly different in the severe sepsis/shock group when all
      groups were compared (both p < 0.05). Additionally, the latter were significantly
      elevated in the severe sepsis/shock group at multiple time points (all p <= 0.05)
      with the peak occurring on day 2 of illness. In a separate analysis, 32% of
      systemic inflammatory response syndrome/sepsis and 82% of severe sepsis/shock had
      variable angiopoietin-2/1 ratio patterns compared with none in the control group
      (p < 0.001). CONCLUSIONS: Pediatric patients with severe sepsis and septic shock
      possess significantly elevated angiopoietin-2/1 ratios during their first 3 days
      of illness, which peak at day 2 of illness. A subset of these patients
      demonstrated variable angiopoietin-2/1 ratio patterns.

PMID- 24141661
TI  - Exchangeability of amino acid residues with similar physicochemical properties in
      coiled-coil interactions.
AB  - Systematic exchange of amino acid residues of similar physicochemical properties
      maintains specific coiled-coil interaction between two heptad repeats of HIV-1
      gp41, as well as the biological activity of related peptide fusion inhibitors.
      This exchangeability can greatly degenerate sequence space of peptides thus
      making ab initio design of coiled-coil interaction feasible. 

PMID- 24141662
TI  - A nitinol based flexor tendon fixation device: gapping and tensile strength
      measurements in cadaver flexor tendon.
AB  - In this study, a new nitinol based fixation device was investigated for use in
      repairing severed digital flexor tendons. The device, composed of superelastic
      nitinol, is tubular in shape with inward facing tines for gripping tissue. Its
      cellular structure was designed such that it has a large effective Poisson's
      ratio, which facilitates a "finger trap" effect. This allows for reduced tendon
      compression during a resting state (to permit vascular perfusion) and increased
      compression during loading (to drive the tines into the tissue for gripping). To
      test the feasibility of using this device for flexor tendon repair, it was tested
      on cadaver flexor digitorum profundus tendons. The tendons were excised, cut in
      the region corresponding to a zone II laceration, and repaired using the device.
      The device was easy to install and did not prevent the tendon from bending.
      Constant strain rate tensile testing revealed a mean tensile strength of 57.6 +/-
      7.7 N, with a force of 53.2 +/- 7.8 N at a 2 mm gap. This exceeds the suggested
      primary repair strength of 45 N, which has been proposed as the necessary
      strength for enabling early mobilization. Although considerable future studies
      will be needed to determine the suitability of the new repair device for clinical
      use, this study demonstrates the feasibility of utilizing a tubular, nitinol
      repair device for flexor tendon fixation.

PMID- 24141665
TI  - But, after all, why is it important to assess the auditory processing?

PMID- 24141666
TI  - Auditory satisfaction of patients fitted with hearing aids in the Brazilian
      Public Health Service and benefits offered by the hearing aids.
AB  - OBJECTIVE: To assess the benefits and degree of satisfaction of adult and elderly
      patients fitted with hearing aids in a service accredited by the Brazilian Public
      Health Service. METHOD: This descriptive cross-sectional study included 34
      individuals with bilateral hearing loss aged 18 and above who had never been
      offered hearing aids. Scales "Hearing Handicap Inventory for Adults" and "Hearing
      Handicap Inventory for the Elderly Screening Version" were used to assess the
      benefits yielded by the hearing aids. Scale "Satisfaction with Amplification in
      Daily Life" was used to gauge patient satisfaction. The first two were applied on
      the day the patients were fitted with hearing aids and one month later, whereas
      the third was applied only one month after the patients had been fitted with the
      hearing aids. RESULTS: After the subjects were offered hearing aids, significant
      reductions were seen in the difficulties they experienced as a consequence of
      hearing loss. The scores in the Satisfaction with Amplification in Daily Life
      scale indicated a high degree of satisfaction among patients. These results were
      not statistically different when gender and age (adult/elderly) subgroups were
      compared. CONCLUSION: The subjects included in the study have benefitted from
      being fitted with hearing aids and have been very happy with the outcome of the
      treatment.

PMID- 24141667
TI  - Gustatory and olfactory dysfunction in laryngectomized patients.
AB  - After total laryngectomy surgery, nasal airflow is moved permanently to the
      tracheostomy opening, compromising the contact of odorant molecules with the
      nasal cavity, which may reflect changes in the olfactory and gustatory perception
      in these individuals. OBJECTIVE: To evaluate the functions of smell and taste in
      total laryngectomized patients. STUDY DESIGN: a study of series. METHOD: The
      sample included a group of 25 patients submitted to total laryngectomy and
      another group of 25 patients who did not underwent the procedure. The taste
      function was evaluated by gustatory strips of filter paper. To assess the
      olfactory function we employed the Brief Smell Identification Test. RESULTS:
      Among the laryngectomized patients there was more hypogeusia (80%, p < 0.05), as
      well as hyposmia (88%, p < 0.001), alone and concomitant (72%, p < 0.001).
      Concerning flavor discrimination, the bitter taste did not differ between the
      groups - which was different from the other flavors. In the olfactory aspect,
      laryngectomized patients performed worse in detecting warning and food-related
      odors. We found that a history of smoking and alcohol consumption were
      significantly more frequent among laryngectomized patients. CONCLUSION: We found
      a decrease of gustatory and olfactory functions in total laryngectomized patients
      in this study.

PMID- 24141668
TI  - Degree of satisfaction of patients fitted with hearing aids at a high complexity
      service.
AB  - Some individuals with hearing loss choose to be fitted with hearing aids.
      Compliance is significantly affected by how satisfied patients are with their
      hearing aids. Patient satisfaction can be assessed through questionnaires and
      scales. OBJECTIVE: To assess the degree of satisfaction of patients fitted with
      hearing aids. METHOD: Scale "Satisfaction With Amplification in Daily Life"
      (SADL) was applied to 180 patients fitted with hearing aids; results were
      categorized based on the mean values observed for global satisfaction scores and
      scores attained on each subscale. Patients were interviewed for additional
      information. RESULTS: Mean global score was 5.6; 48.9% of the subjects were very
      satisfied, 47.2% were satisfied, and 3.9% were dissatisfied. The mean score on
      subscale Positive Effects was 5.6; the mean score for Service and Cost was 6.2;
      for Negative Factors the mean score was 4.9; and the mean score on subscale
      Personal Image was 5.8. Of the patients fitted with in-the-ear hearing aids,
      83.3% were very satisfied. Fifteen percent of the individuals were dissatisfied
      with their Personal Image. Sensorineural and profound hearing loss patients were
      less satisfied, with 5.4% and 50.0% of the subjects revealing dissatisfaction
      with their hearing aids. CONCLUSION: Patients were generally very satisfied with
      their hearing aids. Satisfaction rates were higher among patients fitted with in
      the-ear hearing aids. Dissatisfaction was higher in subscale Personal Image.
      Lesser degrees of satisfaction were seen in patients with sensorineural and
      profound hearing loss.

PMID- 24141669
TI  - Surgical treatment of severe laryngomalacia: a retrospective study of 11 case.
AB  - Laryngomalacia is the most frequent congenital abnormality of the larynx,
      accounting for approximately 60-75% of congenital stridor cases. Despite its
      benign and self-limited aspects, 10% of cases require intervention. Currently,
      supraglottoplasty is considered the standard treatment of severe laryngomalacia.
      OBJECTIVE: To describe the experience of the authors in the surgical treatment of
      patients with severe laryngomalacia. METHODOLOGY: A retrospective study. METHOD:
      The medical records of 11 consecutive cases of severe laryngomalacia who
      underwent surgical treatment between 2003 and 2012 were analyzed for age, gender,
      symptoms, associated diseases, surgical technique employed, extubation time,
      surgical complications, length of hospital stay and clinical outcome. RESULTS: Of
      the 11 cases of severe laryngomalacia, six patients (54.5%) were operated with
      the use of CO2 laser and five patients (45.5%) were submitted to the cold
      technique. Only 1 patient (9.1%) required surgical reintervention. There were no
      cases of surgical complications. All patients had clinical improvement.
      CONCLUSION: Supraglottoplasty proved to be effective and safe in the treatment of
      severe laryngomalacia.

PMID- 24141670
TI  - The impact of environmental factors on quality of life and symptoms of children
      with allergic rhinitis.
AB  - Allergic rhinitis is an inflammation of the nasal mucosa caused by exposure to
      allergens, which impairs the cognitive capabilities of the affected. OBJECTIVE:
      To correlate the mean scores of quality of life of children and adolescents with
      symptoms of allergic rhinitis and the presence of household environmental factors
      described in the literature as allergy triggers. METHOD: This cross-sectional
      retrospective cohort study included 120 children and adolescents presenting
      clinical manifestations of allergic rhinitis. The subjects were divided into two
      groups based on the number of allergy-triggering environmental factors seen in
      their households. Scale PedsQL 4.0 was used to quantify quality of life and allow
      further comparisons between groups. RESULTS: No statistically significant
      differences (p > 0.05) were seen in the PedsQL mean scores when participant
      quality of life was analyzed vis-a-vis triggering environmental factors. However,
      the incidence of allergy manifestations was higher in children exposed to more
      environmental factors. CONCLUSION: The studied environmental factors were not
      correlated with patient quality of life. However, the analysis of patient
      households and symptoms indicates the environment played a role in the onset of
      allergy events.

PMID- 24141671
TI  - Internal nasal dimensions of adults with nasal obstruction.
AB  - Nasal septum deviation (SD) and turbinate hypertrophy (TH) increase the
      resistance to respiratory airflow and may impair nasal patency. OBJECTIVE: To
      characterize the nasal geometry of individuals with nasal obstruction secondary
      to SD and/or TH by means of acoustic rhinometry. METHOD: This prospective study
      included 30 adults with complaints of nasal obstruction (NO) and SD + TH (n =
      24), SD (n = 5) or TH (n = 1) seen by clinical examination. The cross-sectional
      areas of the three main dips of the rhinogram (CSA1, CSA2, CSA3), the distance
      between them and the nostrils (dCSA1, dCSA2, dCSA3), and the volumes of segments
      1.0-3.2 cm (V1), 3.3-6.4 cm (V2), and 7.0-12.0 cm (V3) were measured before and
      after nasal decongestion (DN). For analysis, right and left cross-sectional areas
      and volumes were added and mean dCSA was calculated. RESULTS: Mean values
      (standard deviation) before ND were: 0.83 +/- 0.23 (CSA1), 1.66 +/- 0.52 (CSA2),
      and 2.36 +/- 0.77 (CSA3) cm2; 2.19 +/- 0.20 (dCSA1), 4.01 +/- 0.33 (dCSA2), and
      5.85 +/- 0.37 (dCSA3) cm; 2.77 +/- 0.51 (V1), 6.52 +/- 1.99 (V2), and 26.00 +/-
      9.62 (V3) cm3; all values were lower than laboratory reference values (p < 0.05).
      ND led to proportionally greater increases of sectional areas and volumes in the
      NO group, suggesting an associated functional component. Individual analysis
      revealed 12 cases with normal results despite nasal obstruction. CONCLUSION: Most
      patients with structural nasal obstruction had results suggestive of nasal
      patency impairment in acoustic rhinometry.

PMID- 24141672
TI  - Analysis of otoacoustic emissions in neonates at term and preterm.
AB  - The transient evoked otoacoustic emissions (TEOAEs) have been widely used in
      neonatal hearing screening. OBJECTIVE: To compare the TEOAEs in newborns at term
      and preterm vis-a-vis the following variables: ear side, gender, frequency
      spectrum and gestational age. METHOD: By means of a cross-sectional cohort of 66
      newborns up to the 28th day of life (41 newborns at term and 25 premature
      babies), we recorded TEOAEs. All the individuals did not have risk indicators for
      hearing loss. RESULTS: There was a signal/noise ratio improvement with frequency
      increase. No differences were observed between genders and between the ears, but
      there were differences among the children born at term and preterm in the
      frequency bands at 3 kHz and 4 kHz. CONCLUSION: The TEOAEs test is important for
      assessing the peripheral auditory system of newborns at term and preterm, making
      it possible to have responses regardless of gender and gestational age.

PMID- 24141673
TI  - Prevalence of signs and symptoms of laryngopharyngeal reflux in snorers with
      suspected obstructive sleep apnea.
AB  - OBJECTIVE: To study the prevalence of signs and symptoms of reflux in snorers
      with suspected OSA. METHOD: This cross-sectional study enrolled 74 patients
      assessed positive for OSA with the Berlin questionnaire. The subjects were
      followed up at the sleep disorder ward of a university center. Studied variables
      included the BMI, the Epworth sleepiness scale, the reflux symptom index (RSI),
      the reflux finding score (RFS), and their subdomains related to increased
      inflammation. The correlations between sleep questionnaires, reflux scales, and
      their subdomains were deemed statistically significant when p < 0.05. RESULTS:
      Ninety-eight percent of the subjects had symptoms and signs suggestive of LPR;
      prevalence was significantly higher among obese individuals (p = 0.002).
      CONCLUSION: The significant difference seen in the prevalence of signs of
      inflammation suggestive of LPR when obese and non-obese subjects with suspected
      OSA were compared indicates that obesity may affect inflammatory findings of the
      pharynx and larynx. The high prevalence of symptoms and signs of reflux in
      patients with suspected OSA calls for more studies on the matter.

PMID- 24141674
TI  - The impact of stimulation rates in vestibular evoked myogenic potential testing.
AB  - Vestibular evoked myogenic potentials (VEMP) have been used in complementary
      otoneurological assessment, but the use of VEMP in clinical settings is limited.
      VEMPs can be used to assess vestibular function, particularly of the saccule, the
      inferior vestibular nerve, and/or the vestibular nucleus. OBJECTIVE: To verify
      the highest possible - and reliable - stimulation rate to obtain VEMPs. METHOD:
      The VEMPs of 18 subjects were acquired using stimulation rates ranging between
      5.1 and 40.8 stimuli per second. STUDY DESIGN: cross-sectional contemporary
      cohort study. RESULTS: Latencies were kept unaltered and amplitudes were
      progressively reduced as stimulation rates were increased. However, ANOVA and the
      Kruskal-Wallis test failed to find statistically significant differences between
      the tested parameters. The study further indicated that when stimulation rates of
      5.1 and 10.2 stimuli per second were compared, no statistically significant
      differences were observed in latency. CONCLUSION: The highest reliable
      stimulation rate observed in the group of young adults with normal hearing
      included in this study was 10.2 stimuli per second.

PMID- 24141675
TI  - Determination of HPV prevalence in oral/oropharyngeal mucosa samples in a rural
      district of Sao Paulo.
AB  - Knowledge about HPV infection in the oral cavity/oropharynx may contribute to the
      elucidation of the role it plays in Head and Neck Squamous Cell Carcinoma
      (HNSCC). OBJECTIVE: To determine the effectiveness of the methodology used for
      sampling the oral cavity and oropharynx mucosae and to determine the prevalence
      of HPV in the oral cavity and oropharynx of adults and children. METHOD: The
      study population was served by an assistance program in a rural district of Sao
      Paulo. The subjects were asked to donate samples regardless of complaints.
      RESULTS AND CONCLUSION: The study included 47 men, 77 women and 22 children, of
      which the oral cavity samples were obtained by gargling with commercially
      available antiseptic mouthwash. We found 3 positive samples (2.4%) in adults: 2
      HPV 55 and one HPV 58. No positive results were found in children. Furthermore we
      concluded that the sampling method with the mouthwash proved effective and fast
      for the detection of HPV in the oral cavity and oropharynx in the general
      population.

PMID- 24141677
TI  - Cognitive potential of children with attention deficit and hyperactivity
      disorder.
AB  - The literature has described comorbidities among the symptoms of children with
      Attention Deficit and Hyperactivity Disorder (ADHD) and the auditory processing
      changes, and these symptoms have been overlooked in the assessment, and
      consequently, on the rehabilitation of these individuals. OBJECTIVE: To compare
      the findings of the long latency auditory evoked potentials in children with and
      without ADHD. METHOD: This is a historical cohort cross-sectional case-control
      study, in which we enrolled 30 children with and without ADHD, aged 8-12 years.
      We performed the long-latency auditory evoked potential test in two scanning
      procedures through passive and active tasks differing in frequency and duration
      (MMNf and MMNd) (P300f and P300D). RESULTS: When comparing the performance of
      children with and without ADHD in the electrophysiological test assessment of
      hearing, we found significant differences concerning the P2 amplitude in the LE -
      which was higher for the ADHD group; and concerning the N2 amplitude and latency 
      which were abnormal in the ADHD group. CONCLUSION: This study provided a greater
      understanding of the central auditory pathways of children with and without ADHD
      when evaluated from electrophysiological tests.

PMID- 24141676
TI  - Tonsillar hyperplasia and recurrent tonsillitis: clinical-histological
      correlation.
AB  - Hypertrophy and recurrent tonsillitis are common indications of tonsillectomy.
      However, the pathological reports are similar, regardless of clinical aspects.
      OBJECTIVE: Search for histopathological changes that differentiate palatine
      tonsils operated because of hypertrophy vis-a-vis those operated because of
      recurrent tonsillitis. METHOD: A prospective cross-sectional descriptive study
      involving 46 children divided into group I - 22 with hypertrophy; and group II -
      24 with recurrent tonsillitis, in the period between 2010 and 2012, in a public
      hospital. We evaluated clinical and histopathological features (lymph follicles,
      germinal centers, fibrosis, necrosis, reticulation, infiltration by plasma cells
      and neutrophils). RESULTS: The patients' ages ranged between 2 and 11 years (5.17
      +/- 2.28). In group I, half of the patients had had the latest infection at seven
      months or more, and all with obstruction degree greater than 3 (> 50%). In group
      II, all had had the latest infection at less than seven months, and most with
      obstruction degree below 4 (< 75%). There was a statistically significant
      difference in the degree of obstruction (p = 0.0021) and number of germinal
      centers (p = 0.002) was higher in group I. CONCLUSION: This study suggests that
      the number of germinal centers is the only histopathological criterion that can
      be used to differentiate the two groups.

PMID- 24141678
TI  - Interleukin-17A expression in patients presenting with nasal polyposis.
AB  - Sinonasal polyposis (SNP) is a chronic inflammatory pathology of the
      nasal/paranasal cavities which affects from 1%-4% of the population. Although
      polyps seem to be a manifestation of chronic inflammation of nasal/paranasal
      sinus mucosa in both allergic and non-allergic subjects, the pathogenesis of
      nasal polyposis remains unknown. Interleukin-17A (IL-17A) is a key inflammatory
      cytokine in many disorders. Little attention has been paid to the role of IL-17A
      in chronic inflammatory disorders. OBJECTIVE: To investigate the expression of IL
      17A in the SNP and verify if this expression is a marker of good or bad
      prognosis. METHOD: Prospective study with 25 patients presenting with SNP were
      subjected to the immunohistochemistry technique. After a skin prick test, all
      patients were divided into atopic and nonatopic groups, and asthmatic or non
      asthmatic. RESULTS: The IL-17A expression was observed in both atopic and
      nonatopic patients. The numbers of IL-17A positive cells were greater in nasal
      polyps of atopic patients than nonatopic (p = 0.0128). CONCLUSION: These results
      indicate that IL-17A may play an important role in the pathology of SNP.
      Considering the inflammatory properties of IL-17A, this study suggests that it
      could increase susceptibility to atopy and asthma.

PMID- 24141679
TI  - Mouth breathing in children with learning disorders.
AB  - Given the importance of studying the causes of learning disorders, we designed
      this case-control study to assess the nasal cavity volume, pharyngeal and
      palatine tonsils in children with and without learning disabilities. METHOD: A
      total of forty-eight children were enrolled in the study: twenty-four coming from
      the Center for Evaluation and Early Stimulation (CADEP), in which the criterion
      is the school failure of at least two consecutive years; and twenty-four students
      with normal learning - which made up the control group. The children were
      submitted to ENT examination (history, physical examination) and specific tests
      (acoustic rhinometry, cavum radiography). RESULTS: The results showed that
      students with learning disabilities have a higher prevalence of pharyngeal tonsil
      hypertrophy: p < 0.001, and palatine tonsil hypertrophy: p < 0.001. The average
      volume of the nasal cavities showed no statistically significant association with
      learning difficulties (p = 0.75). CONCLUSION: Based on this study, we concluded
      that children with adenotonsillar hypertrophy have more learning difficulties
      when compared to children without such hypertrophy.

PMID- 24141680
TI  - Value of immunohistochemistry in the diagnosis of malignant cervical lymph nodes.
AB  - The cervical lymph nodes are relevant due to the diversity of clinical entities.
      The use of immunohistochemistry is a real method to elucidate the diagnosis of
      adenopathy, both primary and metastatic neoplasms. OBJECTIVE: To assess the value
      of immunohistochemistry in the diagnosis of cervical lymph nodes malignancies.
      METHOD: Retrospective study of the database histopathological specimens from 2009
      to 2011. RESULTS: Out of 32 biopsies of cervical lymph nodes, in 16 (50%) the
      immunohistochemistry was employed, being 68.75% (11) in hematological neoplasms
      and 31.25% (5) in carcinomas. It was used in all cases of lymphoma. CONCLUSION:
      The immunohistochemistry was used in 50% of the biopsies of lymph nodes under
      suspicion of malignancy, being 31.25% in epithelial lesions and 68.75% in
      lymphoproliferative lesions.

PMID- 24141681
TI  - Influence of signal processing strategy in auditory abilities.
AB  - The signal processing strategy is a parameter that may influence the auditory
      performance of cochlear implant and is important to optimize this parameter to
      provide better speech perception, especially in difficult listening situations.
      OBJECTIVE: To evaluate the individual's auditory performance using two different
      signal processing strategy. METHOD: Prospective study with 11 prelingually
      deafened children with open-set speech recognition. A within-subjects design was
      used to compare performance with standard HiRes and HiRes 120 in three different
      moments. During test sessions, subject's performance was evaluated by warble-tone
      sound-field thresholds, speech perception evaluation, in quiet and in noise.
      RESULTS: In the silence, children S1, S4, S5, S7 showed better performance with
      the HiRes 120 strategy and children S2, S9, S11 showed better performance with
      the HiRes strategy. In the noise was also observed that some children performed
      better using the HiRes 120 strategy and other with HiRes. CONCLUSION: Not all
      children presented the same pattern of response to the different strategies used
      in this study, which reinforces the need to look at optimizing cochlear implant
      clinical programming.

PMID- 24141682
TI  - Surgical treatment and adjuvant therapies of recurrent respiratory
      papillomatosis.
AB  - Recurrent respiratory papillomatosis or recurrent laryngeal papillomatosis is a
      disease of the larynx caused by human papilloma virus, characterized by verrucous
      epithelial lesions and usually recurring. In the literature there are several
      types of treatment, such as surgery to cold, laser and/or use of microdebrider,
      as of adjuvant therapies; all possible to decrease the permanent sequelae of the
      disease. OBJECTIVE: To review the literature regarding this disease with emphasis
      on surgical techniques and adjuvant therapies used today. METHOD: We used the
      literature review, through surveys based electronic data in the public domain, to
      search for articles between 1992-2012, using keywords: papilloma, human papilloma
      virus infection, larynx, therapeutic, papilloma virus vaccine. RESULTS: We
      surveyed 357 articles, of which 49 were used as the basis for this review.
      Scientific studies indicate a reduction of relapse in most adjuvant therapeutic
      presented. However, the survey showed different methodologies and samples, which
      did not allow to compare the types of treatment and adjuvant therapies.
      CONCLUSION: The choice of surgical technique varies among studies, but there is a
      trend to use the microdebrider. The newer adjuvant therapies, such as cidofovir,
      quadrivalent vaccine against human papilloma virus and bevacizumab, require
      further studies.

PMID- 24141683
TI  - Otogenic spontaneous pneumocephalus: case report.

PMID- 24141684
TI  - Thornwaldt cyst--treatment with diode laser.

PMID- 24141685
TI  - Small cell lung carcinoma metastasis to palatine tonsils.

PMID- 24141686
TI  - Extranasopharyngeal angiofibroma of the nasal septum--uncommon presentation of a
      rare disease.

PMID- 24141689
TI  - Religion, kinship and health behaviors of African American women.
AB  - A positive relationship exists between functional health and religion. We present
      an empirical definition of religion and describe the key elements of religious
      behavior, building a model that can be used to explore the presumed relationship
      between religion and health. Semi-structured interactive interviews were
      conducted with 22 participants over a 6-month period. Head Start programs and
      churches located in the inner city of a large metropolitan area. Twenty-two
      African American women were aged from 21 to 45. We focus on social relationships
      and propose that prophet-created religions mimic kinship relationships and
      encourage kinship-like cooperation between members. 

PMID- 24141690
TI  - CMP-Sialic Acid Synthetase: The Point of Constriction in the Sialylation Pathway.
AB  - Sialoglycoconjugates form the outermost layer of animal cells and play a crucial
      role in cellular communication processes. An essential step in the biosynthesis
      of sialylated glycoconjugates is the activation of sialic acid to the
      monophosphate diester CMP-sialic acid. Only the activated sugar is transported
      into the Golgi apparatus and serves as a substrate for the linkage-specific
      sialyltransferases. Interference with sugar activation abolishes sialylation and
      is embryonic lethal in mammals. In this chapter we focus on the enzyme catalyzing
      the activation of sialic acid, the CMP-sialic acid synthetase (CMAS), and compare
      the enzymatic properties of CMASs isolated from different species. Information
      concerning the reaction mechanism and active site architecture is included.
      Moreover, the unusual nuclear localization of vertebrate CMASs as well as the
      biotechnological application of bacterial CMAS enzymes is addressed. 

PMID- 24141691
TI  - A plastic total internal reflection photoluminescence device for enzymatic
      biosensing.
AB  - A total internal reflection photoluminescence (TIRPh) device employing an easily
      fabricated PMMA/PDMS waveguide system provides a detection limit comparable to
      the best reported results but without using an excitation filter. The optical
      mechanism is similar to total-internal-reflection-fluorescence (TIRF) but uses a
      ruthenium-based phosphorescent dye (Ru(dpp)3) deposited on the PMMA core,
      motivating the generalized term of photoluminescence to include both fluorescence
      and phosphorescence. An enzymatic hydrogen peroxide (H2O2) biosensor
      incorporating catalase was fabricated on the TIRPh platform without
      photolithography or etching. The O2-sensitive phosphorescence of Ru(dpp)3 was
      used as a transduction mechanism and catalase was used as a biocomponent for
      sensing. The H2O2 sensor exhibits a phosphorescence to scattered excitation light
      ratio of 76 +/- 10 without filtering. The unfiltered device demonstrates a
      detection limit of (2.2 +/- 0.6) MUM with a linear range of 0.1 mM to 20 mM. The
      device is the first total internal reflection photoluminescence based enzymatic
      biosensor platform, and is promising for cost-effective, low excitation
      interference, field-portable sensing. 

PMID- 24141692
TI  - Production of dammarenediol-II triterpene in a cell suspension culture of
      transgenic tobacco.
AB  - Dammarenediol-II is biologically active tetracyclic triterpenoid, which is basic
      compound of ginsenoside saponin. Here, we established the dammarenediol-II
      production via a cell suspension culture of transgenic tobacco overexpressing
      PgDDS. Dammarenediol-II synthase catalyzes the cyclization of 2,3-oxidosqualene
      to dammarenediol-II, which is the basic triterpene skeleton in dammarene-type
      saponin (ginsenosides) in Panax ginseng. Dammarenediol-II is a useful candidate
      both for pharmacologically active triterpenes and as a defense compound in
      plants. Dammarenediol-II is present in the roots of P. ginseng in trace amounts
      because it is an intermediate product in triterpene biosynthesis. In this work,
      we established the production of dammarenediol-II via cell suspension culture of
      transgenic tobacco. The dammarenediol-II synthase gene (PgDDS) isolated from P.
      ginseng was introduced into the Nicotiana tobacum genome under the control of 35S
      promoter by Agrobacterium-mediated transformation. Accumulation of dammarenediol
      II in transgenic tobacco plants occurred in an organ-specific manner (roots >
      stems > leaves > flower buds), and transgenic line 14 (T14) exhibited a high
      amount (157.8 MUg g-1 DW) of dammarenediol-II in the roots. Dammarenediol-II
      production in transgenic tobacco plants resulted in reduced phytosterol (beta
      sitosterol, campesterol, and stigmasterol) contents. A cell suspension culture
      was established as a shake flask culture of a callus derived from root segments
      of transgenic (T14) plants. The amount of dammarenediol-II production in the cell
      suspension reached 573 MUg g-1 dry weight after 3 weeks of culture, which is
      equivalent to a culture volume of 5.2 mg dammarenediol-II per liter.
      Conclusively, the production of dammarenediol-II in a cell suspension culture of
      transgenic tobacco can be applied to the large-scale production of this compound
      and utilized as a source of pharmacologically active medicinal materials.

PMID- 24141693
TI  - FDTD computation of temperature elevation in the elderly for far-field RF
      exposures.
AB  - Core temperature elevation and perspiration in younger and older adults is
      investigated for plane-wave exposure at whole-body averaged specific absorption
      rate of 0.4 W kg(-1). Numeric Japanese male model is considered together with a
      thermoregulatory response formula proposed in the authors' previous study. The
      frequencies considered were at 65 MHz and 2 GHz where the total power absorption
      in humans becomes maximal for the allowable power density prescribed in the
      international guidelines. From the computational results used here, the core
      temperature elevation in the older adult model was larger than that in the
      younger one at both frequencies. The reason for this difference is attributable
      to the difference of sweating, which is originated from the difference in the
      threshold activating the sweating and the decline in sweating in the legs. 

PMID- 24141694
TI  - Is the supine position superior to the prone position for percutaneous
      nephrolithotomy (PCNL)?
AB  - The objective of this study is to update the two previous meta-analyses in order
      to evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) for
      patients in the prone position versus supine position. An electronic database
      search of MEDLINE, EMBASE, google scholar, and the Cochrane library was performed
      up to June, 2013. All studies comparing prone with supine position for PCNL were
      included. The outcome measures were stone-free rate, operative time, complication
      and hospital stay. Two randomized controlled trials (RCTs) and 7 non-RCTs,
      including 6,413 patients (4,956 patients in the prone position group and 1,457
      patients in the supine position group), met the inclusion criteria. Meta-analysis
      of extractable data showed that PCNL in the supine position was associated with a
      significantly shorter operative time (WMD: 21.7; 95% CI 2.46-40.94; p = 0.03) but
      lower stone-free rate (OR: 1.36; 95% CI 1.19-1.56; p < 0.0001) than PCNL in the
      prone position. There was no difference between the two positions regarding
      hospital stay (WMD = 0.05; 95% CI -0.16-0.25; p = 0.66) and complication rate
      (OR: 1.1; 95% CI 0.94-1.28; p = 0.24). In conclusion, the present study found
      different results from the two previous meta-analyses results regarding stone
      free rate; PCNL in the supine position had a significantly lower stone-free rate
      than that in prone position.

PMID- 24141695
TI  - Quantifying the effect of temporal resolution on time-varying networks.
AB  - Time-varying networks describe a wide array of systems whose constituents and
      interactions evolve over time. They are defined by an ordered stream of
      interactions between nodes, yet they are often represented in terms of a sequence
      of static networks, each aggregating all edges and nodes present in a time
      interval of size Deltat. In this work we quantify the impact of an arbitrary
      Deltat on the description of a dynamical process taking place upon a time-varying
      network. We focus on the elementary random walk, and put forth a simple
      mathematical framework that well describes the behavior observed on real
      datasets. The analytical description of the bias introduced by time integrating
      techniques represents a step forward in the correct characterization of dynamical
      processes on time-varying graphs. 

PMID- 24141696
TI  - Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via
      targeting HSP47 in cervical squamous cell carcinoma.
AB  - Our recent studies of microRNA (miRNA) expression signatures indicated that
      microRNA-29a (miR-29a) was significantly downregulated in several types of human
      cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in
      human cancers. The aim of this study was to investigate the functional
      significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify
      novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC
      oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines
      (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited
      cancer cell migration and invasion. Gene expression data and in silico analysis
      demonstrated that heat-shock protein 47 (HSP47), a member of the serpin
      superfamily of serine proteinase inhibitors and a molecular chaperone involved in
      the maturation of collagen molecules, was a potential target of miR-29a
      regulation. Luciferase reporter assays showed that miR-29a directly regulated
      HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell
      migration and invasion in cancer cells and the expression of HSP47 was
      upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as
      demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in
      cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47.
      Recognition of tumor-suppressive miRNA-regulated molecular targets provides new
      insights into the potential mechanisms of cervical SCC oncogenesis and metastasis
      and suggests novel therapeutic strategies for treatment of this disease.

PMID- 24141697
TI  - Perceived empowerment in people with a dual diagnosis of schizophrenia spectrum
      disorder and substance misuse.
AB  - PURPOSE: The aims of the present study were to validate a measure of empowerment
      in a British population of people with a dual diagnosis of schizophrenia and
      substance misuse and assess relationships between empowerment and other key
      outcomes. METHOD: Patients participating in a large randomised control trial for
      Motivational Interviewing for Drug and Alcohol misuse in Schizophrenia or
      psychosis (MIDAS trial) completed measures of empowerment, symptoms, global
      functioning and substance use at baseline, 12- and 24-month follow-ups. RESULTS:
      A three factor model of empowerment: self-efficacy and control; power and anger;
      and activism provided the best fit of the data across all three time points.
      There was some evidence of associations between empowerment and both symptoms and
      global functioning, although these associations were not consistent across
      subscales. Changes in empowerment predicted changes in symptoms and functioning
      at follow-up. CONCLUSIONS: Empowerment is a broadly defined construct and its
      meaning may differ across different populations of people with severe and
      enduring mental health problems. Empowerment is a key component of recovery and
      should be assessed in treatments in addition to more traditional outcome measures
      of symptoms and functioning.

PMID- 24141698
TI  - Pooled analysis of phase III clinical studies of palonosetron versus ondansetron,
      dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and
      vomiting (CINV).
AB  - PURPOSE: Preventing chemotherapy-induced nausea and vomiting (CINV) is integral
      to treatment success in patients with cancer. This analysis was undertaken to
      assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in
      preventing CINV associated with moderately or highly emetogenic chemotherapy.
      METHODS: Patient-level data from four randomized, double-blind, phase III trials
      comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg,
      or granisetron 40 MUg/kg were analyzed. Endpoints included complete response (CR:
      no emesis and no rescue antiemetics) in the acute (0-24 h), delayed (>24-120 h),
      and overall (0-120 h) postchemotherapy periods (primary), complete control (CC:
      no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic
      episodes, and nausea severity. RESULTS: CR rates were significantly higher for
      palonosetron (n = 1,787) versus older 5HT3 RAs (n = 1,175) in the delayed (57 vs
      45 %, P < 0.0001) and overall periods (51 vs 40 %, P < 0.0001); odds ratios (95 %
      CI) in the acute, delayed, and overall periods were 1.15 (0.98-1.34), 1.62 (1.40
      1.88), and 1.56 (1.34-1.81), respectively. Significant differences in CC rates
      and nausea severity were observed for the delayed and overall periods and in
      emetic episodes for all three periods. The incidence of treatment-related adverse
      events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older
      5HT3 RAs (27.5 %). CONCLUSIONS: Palonosetron is more effective than older 5HT3
      RAs for controlling CINV in the delayed and overall postchemotherapy periods.

PMID- 24141699
TI  - Serious postoperative infections following resection of common solid tumors:
      outcomes, costs, and impact of hospital surgical volume.
AB  - PURPOSE: Unlike infections related to chemotherapy-induced neutropenia,
      postoperative infections occurring in patients with solid malignancy remain
      largely understudied. Our aim is to evaluate the outcomes and the volume-outcomes
      relationship associated with postoperative infections following resection of
      common solid tumors. METHODS: We used Texas Discharge Data to study patients
      undergoing resection of cancer of the lung, esophagus, stomach, pancreas, colon,
      or rectum from 01/2002 to 11/2006. From their billing records, we identified ICD
      9 codes indicating a diagnosis of serious postoperative infection (SPI), i.e.,
      bacteremia/sepsis, pneumonia, and wound infection, occurring during surgical
      admission or leading to readmission within 30 days of surgery. Using regression
      based techniques, we estimated the impact of SPI on mortality, resource
      utilization, and costs, as well as the relationship between hospital volume and
      SPI, after adjusting for confounders and data clustering. RESULTS: SPI occurred
      following 9.4 % of the 37,582 eligible tumor resections and was independently
      associated with nearly 12-fold increased odds of in-hospital mortality [95 %
      confidence interval (95 % CI), 7.2-19.5, P < 0.001]. Patients with SPI required
      six additional hospital days (95 % CI, 5.9-6.2) at an incremental cost of $16,991
      (95 % CI, $16,495-$17,497). Patients who underwent resection at high-volume
      hospitals had a 16 % decreased odds of developing SPI than those at low-volume
      hospitals (P = 0.03). CONCLUSIONS: Due to the substantial burden associated with
      SPI following common solid tumor resections, hospitals must identify more
      effective prophylactic measures to avert these potentially preventable
      infections. Additional volume-outcomes research is needed to identify infection
      prevention processes that can be transferred from high- to lower-volume
      providers.

PMID- 24141700
TI  - Development and validation of a cancer-specific swallowing assessment tool: MASA
      C.
AB  - OBJECTIVE: We present data from a sample of patients receiving radiotherapy for
      head/neck cancer to define and measure the validity of a new clinical assessment
      measure for swallowing. METHODS: Fifty-eight patients undergoing radiotherapy (+/
      chemotherapy) for head/neck cancer (HNC) supported the development of a
      physiology-based assessment tool of swallowing (Mann Assessment of Swallowing
      Ability--Cancer: MASA-C) administered at two time points (baseline and following
      radiotherapy treatment). The new exam was evaluated for internal consistency of
      items using Cronbach's alpha. Reliability of measurement was evaluated with
      intraclass correlation (ICC) and the Kappa statistic between two independent
      raters. Concurrent validity was established through comparison with the original
      MASA examination and against the referent standard videofluoroscopic swallowing
      examination (VFE). Sensitivity, specificity, and likelihood ratios along with 95
      % confidence intervals (CIs) were derived for comparison of the two evaluation
      forms (MASA vs. MASA-C). Accuracy of diagnostic precision was displayed using
      receiver operator characteristic curves. RESULTS: The new MASA-C tool
      demonstrated superior validity to the original MASA examination applied to a HNC
      population. In comparison to the VFE referent exam, the MASA-C revealed strong
      sensitivity and specificity (Se 83, Sp 96), predictive values (positive
      predictive value (PPV) 0.95, negative predictive value (NPV) 0.86), and
      likelihood ratios (21.6). In addition, it demonstrated good reliability (ICC =
      0.96) between speech-language pathology raters. CONCLUSIONS: The MASA-C is a
      reliable and valid scale that is sensitive to differences in swallowing
      performance in HNC patients with and without dysphagia. Future longitudinal
      evaluation of this tool in larger samples is suggested. The development and
      refinement of this swallowing assessment tool for use in multidisciplinary HNC
      teams will facilitate earlier identification of patients with swallowing
      difficulties and enable more efficient allocation of resources to the management
      of dysphagia in this population. The MASA-C may also prove useful in future
      clinical HNC rehabilitation trials with this population.

PMID- 24141701
TI  - Change in carers' activities after the death of their partners.
AB  - PURPOSE: When a person is dying and during bereavement, family members often put
      their lives on hold to provide full-time care. Meaningful activities may be
      curtailed or forgotten. This study described the activities that changed between
      pre- and post-caring, and what factors assisted carers to re-engage in activities
      2 years following the death of their partners. METHODS: A mixed methods design
      included a cross-sectional survey and face-to-face interviews. The study occurred
      in 2009 with 40 females that cared for a partner who had subsequently died of
      cancer 2 years previously. Engagement in community and other activities was
      determined through use of the Activity Card Sort-Australia and semi-structured
      interviews. The SF-36v2 measured physical and mental health status, and perceived
      social support was measured using the Multidimensional Scale of Perceived Social
      Support. RESULTS: Most carers in our study were more engaged in household
      activities post-caring compared to their pre-caring activities, but had decreased
      social and leisure activities. Living as a single person meant they had taken on
      new roles and responsibilities. Leisure and social activities previously
      associated with subjective well-being and health were reduced or lost. Greater
      social support contributed to a higher retention of activities post-caring.
      CONCLUSIONS: Retention of activities could be facilitated by participation in
      community services, recreational groups and other support and interest groups,
      both during and after caring.

PMID- 24141702
TI  - Far-infrared spectra of well-defined thiolate-protected gold clusters.
AB  - The far infrared spectra of a series of well-defined gold clusters covered with 2
      phenylethanethiolate were studied. The spectra of the clusters are different but
      the differences are subtle. The Au-S stretching vibrations give rise to bands
      around 300 cm(-1) and below. The relative intensity of these bands changes but
      they shift only slightly for different clusters. A low-frequency band was
      identified, which is sensitive to the conformation (trans/gauche) of the 2
      phenylethanethiolate ligand. 

PMID- 24141703
TI  - PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
AB  - EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential
      for development processes in vivo and for the differentiation of embryonic stem
      cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive
      H3K27me3 marks is well understood, but how it is regulated and directed to
      specific genes before and during differentiation remains unknown. Here, we report
      that PRC2 binds at low levels to a majority of promoters in mouse ESCs, including
      many that are active and devoid of H3K27me3. Using in vivo RNA-protein cross
      linking, we show that EZH2 directly binds the 5' region of nascent RNAs
      transcribed from a subset of these promoters and that these binding events
      correlate with decreased H3K27me3. Our findings suggest a molecular mechanism by
      which PRC2 senses the transcriptional state of the cell and translates it into
      epigenetic information. 

PMID- 24141704
TI  - A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq
      and Gi proteins.
AB  - Entomopathogenic Photorhabdus asymbiotica is an emerging pathogen in humans.
      Here, we identified a P. asymbiotica protein toxin (PaTox), which contains a
      glycosyltransferase and a deamidase domain. PaTox mono-O-glycosylates Y32 (or
      Y34) of eukaryotic Rho GTPases by using UDP-N-acetylglucosamine (UDP-GlcNAc).
      Tyrosine glycosylation inhibits Rho activation and prevents interaction with
      downstream effectors, resulting in actin disassembly, inhibition of phagocytosis
      and toxicity toward insects and mammalian cells. The crystal structure of the
      PaTox glycosyltransferase domain in complex with UDP-GlcNAc determined at 1.8-A
      resolution represents a canonical GT-A fold and is the smallest
      glycosyltransferase toxin known. (1)H-NMR analysis identifies PaTox as a
      retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP
      hydrolysis of heterotrimeric Galphaq/11 and Galphai proteins, thereby activating
      RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by
      deamidation-induced activation and glycosylation-induced inactivation of GTPases.

PMID- 24141705
TI  - Mechanism of allosteric activation of SAMHD1 by dGTP.
AB  - SAMHD1, a dNTP triphosphohydrolase (dNTPase), has a key role in human innate
      immunity. It inhibits infection of blood cells by retroviruses, including HIV,
      and prevents the development of the autoinflammatory Aicardi-Goutieres syndrome
      (AGS). The inactive apo-SAMHD1 interconverts between monomers and dimers, and in
      the presence of dGTP the protein assembles into catalytically active tetramers.
      Here, we present the crystal structure of the human tetrameric SAMHD1-dGTP
      complex. The structure reveals an elegant allosteric mechanism of activation
      through dGTP-induced tetramerization of two inactive dimers. Binding of dGTP to
      four allosteric sites promotes tetramerization and induces a conformational
      change in the substrate-binding pocket to yield the catalytically active enzyme.
      Structure-based biochemical and cell-based biological assays confirmed the
      proposed mechanism. The SAMHD1 tetramer structure provides the basis for a
      mechanistic understanding of its function in HIV restriction and the pathogenesis
      of AGS. 

PMID- 24141707
TI  - In situ product removal in fermentation systems: improved process performance and
      rational extractant selection.
AB  - The separation of inhibitory compounds as they are produced in biotransformation
      and fermentation systems is termed in situ product removal (ISPR). This review
      examines recent ISPR strategies employing several classes of extractants
      including liquids, solids, gases, and combined extraction systems. Improvement
      through the simple application of an auxiliary phase are tabulated and summarized
      to indicate the breadth of recent ISPR activities. Studies within the past 5
      years that have highlighted and have discussed "second phase" properties, and
      that have an effect on fermentation performance, are particular focus of this
      review. ISPR, as a demonstrably effective processing strategy, continues to be
      widely adopted as more applications are explored; however, focus on the
      properties of extractants and their rational selection based on first principle
      considerations will likely be key to successfully applying ISPR to more
      challenging target molecules.

PMID- 24141706
TI  - Structural insights into H+-coupled multidrug extrusion by a MATE transporter.
AB  - Multidrug and toxic compound extrusion (MATE) transporters contribute to
      multidrug resistance by coupling the efflux of drugs to the influx of Na(+) or
      H(+). Known structures of Na(+)-coupled, extracellular-facing MATE transporters
      from the NorM subfamily revealed 12 membrane-spanning segments related by a quasi
      two-fold rotational symmetry and a multidrug-binding cavity situated near the
      membrane surface. Here we report the crystal structure of an H(+)-coupled MATE
      transporter from Bacillus halodurans and the DinF subfamily at 3.2-A resolution,
      unveiling a surprisingly asymmetric arrangement of 12 transmembrane helices. We
      also identified a membrane-embedded substrate-binding chamber by combining
      crystallographic and biochemical analyses. Our studies further suggested a direct
      competition between H(+) and substrate during DinF-mediated transport and implied
      how a MATE transporter alternates between its extracellular- and intracellular
      facing conformations to propel multidrug extrusion. Collectively, our results
      demonstrated heretofore-unrecognized mechanistic diversity among MATE
      transporters. 

PMID- 24141708
TI  - Latent profile analysis of observed parenting behaviors in a clinic sample.
AB  - We examined typologies of parenting practices using latent profile analysis (LPA)
      in a sample of families with young children who had externalizing behavior
      disorders. We also examined mother and child characteristics associated with
      class membership using ratings from multiple informants. The sample included
      pooled data from five parenting treatment outcome research studies on
      oppositional defiant disorder (ODD) and/or conduct disorder (CD) conducted
      throughout the past 20 years. These studies included 21 separate cohorts of
      children resulting in a total of 514 families. All children met diagnostic
      criteria for ODD or CD and 78 % were male. Parenting practices were observed by
      independent raters using the Dyadic Parent-child Interactive Coding System
      Revised (DPICS-R). Four summary scores (i.e., total critical statements, total
      commands, total positive, total supportive) from the DPICS-R were used as class
      indictors in the LPA. Four classes best characterized the parenting practices of
      this clinic sample, roughly comprising a quarter of the sample each: Positive
      Only, Negative Only, Positive/Negative, and Neither Positive/Negative. High
      observed child negative behaviors, low observed child warmth, high socioeconomic
      status, and low academic performance distinguished the two classes with high
      negative behaviors (Negative Only, Positive/Negative) from the other classes.
      These results provide markers of the most common parenting profiles at entry into
      treatment programs for behavior disorders in young children. Findings have
      significant implications for the tailoring parenting interventions and supports
      to specific family needs. 

PMID- 24141709
TI  - Executive functioning as a mediator of conduct problems prevention in children of
      homeless families residing in temporary supportive housing: a parallel process
      latent growth modeling approach.
AB  - A culturally diverse sample of formerly homeless youth (ages 6-12) and their
      families (n = 223) participated in a cluster randomized controlled trial of the
      Early Risers conduct problems prevention program in a supportive housing setting.
      Parents provided 4 annual behaviorally-based ratings of executive functioning
      (EF) and conduct problems, including at baseline, over 2 years of intervention
      programming, and at a 1-year follow-up assessment. Using intent-to-treat
      analyses, a multilevel latent growth model revealed that the intervention group
      demonstrated reduced growth in conduct problems over the 4 assessment points. In
      order to examine mediation, a multilevel parallel process latent growth model was
      used to simultaneously model growth in EF and growth in conduct problems along
      with intervention status as a covariate. A significant mediational process
      emerged, with participation in the intervention promoting growth in EF, which
      predicted negative growth in conduct problems. The model was consistent with
      changes in EF fully mediating intervention-related changes in youth conduct
      problems over the course of the study. These findings highlight the critical role
      that EF plays in behavioral change and lends further support to its importance as
      a target in preventive interventions with populations at risk for conduct
      problems. 

PMID- 24141710
TI  - Comparative study of candidate housekeeping genes for quantification of target
      gene messenger RNA expression by real-time PCR in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Mucosal expression of immunological mediators is modified in
      inflammatory bowel disease (IBD). Quantification of target gene messenger RNA
      (mRNA) transcripts depends on the normalization to a housekeeping or reference
      gene. Stability of housekeeping gene expression is critical for the accurate
      measurement of transcripts of the target gene. No studies have addressed the
      optimization of reference gene performance for mRNA studies in healthy intestinal
      mucosa and during mucosal inflammation. METHODS: RNA was extracted from
      endoscopically obtained intestinal biopsies from healthy control subjects and
      patients with active IBD or non-IBD inflammatory diseases. Comparative analysis
      of 10 candidate housekeeping genes for quantitative real-time PCR was carried out
      according to predefined criteria, including use of the Web-based RefFinder
      platform. RESULTS: We demonstrate that intestinal inflammation may significantly
      affect the stability of mucosal expression of housekeeping genes. Commonly used
      controls, such as glyceraldehyde-3-phosphate dehydrogenase, beta-actin, or beta2
      microglobulin displayed high variability within the control group and/or between
      the healthy and inflamed mucosae. In contrast, we have identified novel genes
      with optimal stability, which may be used as appropriate housekeeping controls.
      The ribosomal proteins encoding genes (RPLPO and RPS9) were the most stable
      because their expression was not affected by interindividual differences, the
      presence of inflammation, or intestinal location. Normalization ofthe mRNA
      expression of mucosal tumor necrosis factor-alpha was highly dependent on the
      specific reference gene and varied significantly when normalized to genes with
      high or low stability. CONCLUSIONS: Validation for optimal performance of the
      housekeeping gene is required for target mRNA quantification in healthy intestine
      and IBD-associated lesions. Suboptimal reference gene expression may explain
      conflicting results from published studies on IBD gene expression.

PMID- 24141711
TI  - Increasing incidence and lifetime risk of inflammatory bowel disease in Taiwan: a
      nationwide study in a low-endemic area 1998-2010.
AB  - BACKGROUND: The incidence of inflammatory bowel disease is increasing worldwide,
      but data of epidemiological trends from low-endemic area are limited. As one of
      the low-endemic countries, we describe the trends of this disease in Taiwan over
      time. METHODS: This study was based on data obtained from the Catastrophic
      Illnesses Registration in the National Health Insurance Research Database, which
      covers more than 98% of the people in Taiwan. Every certificate of catastrophic
      illness must be approved by 2 expert gastroenterologists. Thirteen years (1998
      2010) of data were analyzed for the trends of Crohn's disease (CD) and ulcerative
      colitis (UC). RESULTS: A total of 2915 incident cases (1818 men and 1097 women)
      were identified, including 2357 cases of UC and 558 cases of CD. The mean annual
      incidence rates were 0.80 for UC and 0.19 for CD per 100,000 inhabitants, with
      lifetime risks for those 20 to 79 years of age of 0.066% and 0.013%,
      respectively. The mean annual prevalence was 4.59 for UC and 1.05 for CD per
      100,000 inhabitants. Poisson regression showed significantly increased trends
      during the observation period for both diseases, with a men/women ratio of 1.50
      in UC and 2.14 in CD (P < 0.01). The mean age of individuals at diagnosis was
      higher for UC as compared with CD (44.7 versus 37.9, P < 0.001). CONCLUSIONS:
      Inflammatory bowel diseases are still relatively uncommon in Taiwan, but the
      incidence and prevalence rates are increasing.

PMID- 24141712
TI  - G protein-coupled receptor 43 moderates gut inflammation through cytokine
      regulation from mononuclear cells.
AB  - BACKGROUND: Short-chain fatty acids (SCFAs), which are produced by the
      fermentation of dietary fiber by intestinal microbiota, may positively influence
      immune responses and protect against gut inflammation. SCFAs bind to G protein
      coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions
      profoundly affect the gut inflammatory response. METHODS: Colitis was induced by
      adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and
      wild-type mice. RESULTS: Dextran sulfate sodium-treated GPR43 mice exhibited
      weight loss, increased disease activity index (a combined measure of weight loss,
      rectal bleeding, and stool consistency), decreased hematocrit, and colon
      shortening, resulting in significantly worse colonic inflammation than in wild
      type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the
      colonic mucosa of GPR43 mice were significantly higher than in wild-type mice.
      Treatment of wild-type mice with 150 mM acetate in their drinking water markedly
      improved these disease indices, with an increase in colon length and decrease in
      the disease activity index; however, it had no effect on GPR43 mice. Mononuclear
      cell production of tumor necrosis factor alpha after lipopolysaccharide
      stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43
      antibody. CONCLUSIONS: SCFA-GPR43 interactions modulate colitis by regulating
      inflammatory cytokine production in mononuclear cells.

PMID- 24141713
TI  - Epithelial cell-specific MyD88 signaling mediates ischemia/reperfusion-induced
      intestinal injury independent of microbial status.
AB  - The Toll-like receptor/MyD88 signaling pathway has been shown to mediate
      protective functions during intestinal exposure to various noxious events. The
      goal of this study was to define the role of bacteria and MyD88 signaling in
      intestinal response to damage using an ischemia-reperfusion (I/R)-induced injury
      model. We showed that conventionalized mice displayed a better outcome to I/R
      induced injury than germ-free mice (3.8 +/- 1.98 vs. 11.8 +/- 1.83, P < 0.05).
      However, mice with intestinal epithelial cell (IEC)-specific deletion of Myd88
      (Myd88) were protected from I/R-induced injury compared with Myd88 control mice.
      Myd88 mice also displayed a significantly reduced bacterial translocation (~85%)
      into lymph nodes compared with Myd88 mice. Expression of ccl2 and cxcl1 mRNA was
      significantly reduced (85% and 62%, respectively) in intestinal tissue of Myd88
      mice compared with Myd88 mice, which associated with a reduced number of
      myeloperoxidase-positive cells in intestinal tissues of I/R-exposed Myd88 mice.
      Immunohistochemistry analysis showed a reduced IgA deposition and complement
      staining in ischemic tissue of Myd88 mice compared with Myd88 mice. These
      findings suggest that I/R-induced intestinal injury involves IEC-derived MyD88
      signaling leading to increased IgA deposition/degradation, and complement
      activation in conjunction with an influx of neutrophils mediated by chemokine
      production.

PMID- 24141714
TI  - World Medical Association Declaration of Helsinki: ethical principles for medical
      research involving human subjects.

PMID- 24141715
TI  - Improved measurement of the glomerular filtration rate from Tc-99m DTPA
      scintigraphy in patients following nephrectomy.
AB  - OBJECTIVE: We aimed to improve Tc-99m DTPA glomerular filtration rate (GFR)
      scintigraphy (Gates' method) in a prospective study using Cr-51 EDTA GFR test as
      a gold standard. METHODS: Fifty-seven Tc-99m DTPA GFR scintigrams in 45 subjects
      (male/female = 33:12, age = 45.9 +/- 17.6 years, 14 healthy volunteers and 31
      nephrectomised patients) were compared using Cr-51 EDTA GFR tests. Using the
      %renal uptake of Tc-99m DTPA and Cr-51 EDTA GFR, a revised equation for GFR was
      established through linear regression analysis. RESULTS: The revised equation for
      improved GFR was GFR(mL/min) = (%renal uptake * 11.7773) - 0.7354. Gates'
      original GFRs (70.1 +/- 20.5 mL/min/1.73 m(2)) were significantly lower than Cr
      51 EDTA GFRs (97.0 +/- 31.9 mL/min/1.73 m(2); P < 0.0001), but the improved GFRs
      (98.0 +/- 26.3 mL/min/1.73 m(2)) were not different from (P = 0.7360) and had a
      significant correlation with (r = 0.73, P < 0.0001) the Cr-51 EDTA GFRs. The
      revised GFR equation effectively demonstrated perioperative GFR changes in
      kidneys that were operated on and the contralateral kidneys at 3 and 6 months
      post-partial nephrectomy (n = 25). CONCLUSIONS: GFR measurement using Tc-99m DTPA
      scintigraphy could be significantly improved by a revised equation derived from
      the comparison with Cr-51 EDTA GFR. KEY POINTS: * Measurement of glomerular
      filtration rate is difficult following nephrectomy. * Measurements can be
      significantly improved by new renal sctintigraphic methods. * This helps
      physicians to measure kidney function of patients following nephrectomy. *
      Management of renal tumour patients should become more effective.

PMID- 24141716
TI  - Accuracy of dual-energy computed tomography for the measurement of iodine
      concentration using cardiac CT protocols: validation in a phantom model.
AB  - PURPOSE: To assess the accuracy of dual-energy CT (DECT) for the quantification
      of iodine concentrations in a thoracic phantom across various cardiac DECT
      protocols and simulated patient sizes. MATERIALS AND METHODS: Experiments were
      performed on first- and second-generation dual-source CT (DSCT) systems in DECT
      mode using various cardiac DECT protocols. An anthropomorphic thoracic phantom
      was equipped with tubular inserts containing known iodine concentrations (0-20
      mg/mL) in the cardiac chamber and up to two fat-equivalent rings to simulate
      different patient sizes. DECT-derived iodine concentrations were measured using
      dedicated software and compared to true concentrations. General linear regression
      models were used to identify predictors of measurement accuracy RESULTS:
      Correlation between measured and true iodine concentrations (n = 72) across CT
      systems and protocols was excellent (R = 0.994-0.997, P < 0.0001). Mean
      measurement errors were 3.0 +/- 7.0% and -2.9 +/- 3.8% for first- and second
      generation DSCT, respectively. This error increased with simulated patient size.
      The second-generation DSCT showed the most stable measurements across a wide
      range of iodine concentrations and simulated patient sizes. CONCLUSION: Overall,
      DECT provides accurate measurements of iodine concentrations across cardiac CT
      protocols, strengthening the case for DECT-derived blood volume estimates as a
      surrogate of myocardial blood supply. KEY POINTS: * Dual-energy CT provides new
      opportunities for quantitative assessment in cardiac imaging. * DECT can quantify
      myocardial iodine as a surrogate for myocardial perfusion. * DECT measurements of
      iodine concentrations are overall very accurate. * The accuracy of such
      measurements decreases as patient size increases.

PMID- 24141718
TI  - Remodelling of a polypyrimidine tract-binding protein complex during apoptosis
      activates cellular IRESs.
AB  - Post-transcriptional control of gene expression is mediated by the interaction of
      RNA-binding proteins with their cognate mRNAs that specifically regulate their
      stability, localization and translation. mRNA-binding proteins are
      multifunctional and it has been proposed therefore that a combinatorial RNA
      binding protein code exists that allows specific protein sub-complexes to control
      cytoplasmic gene expression under a range of pathophysiological conditions. We
      show that polypyrimidine tract-binding protein (PTB) is central to one such
      complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF
      related apoptosis inducing ligand there is a change in the repertoire of RNA
      binding proteins with which PTB interacts. We show that altering the cellular
      levels of PTB and its binding partners, either singly or in combination, is
      sufficient to directly change the rates of apoptosis with increased expression of
      PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we
      show that these proteins post-transcriptionally regulate gene expression, and
      therefore apoptotic rates, by interacting with and stimulating the activity of
      RNA elements (internal ribosome entry segments) found in mRNAs that are
      translated during apoptosis. Taken together, our data show that PTB function is
      controlled by a set of co-recruited proteins and importantly provide further
      evidence that it is possible to dictate cell fate by modulating cytoplasmic gene
      expression pathways alone. 

PMID- 24141717
TI  - Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release
      and cell death.
AB  - Apoptosis is programmed cell death triggered by activation of death receptors or
      cellular stress. Activation of caspases is the hallmark of apoptosis. Arrestins
      are best known for their role in homologous desensitization of G protein-coupled
      receptors (GPCRs). Arrestins quench G protein activation by binding to activated
      phosphorylated GPCRs. Recently, arrestins have been shown to regulate multiple
      signalling pathways in G protein-independent manner via scaffolding signalling
      proteins. Here we demonstrate that arrestin-2 isoform is cleaved by caspases
      during apoptosis induced via death receptor activation or by DNA damage at
      evolutionarily conserved sites in the C-terminus. Caspase-generated arrestin-2-(1
      380) fragment translocates to mitochondria increasing cytochrome C release, which
      is the key checkpoint in cell death. Cells lacking arrestin-2 are significantly
      more resistant to apoptosis. The expression of wild-type arrestin-2 or its
      cleavage product arrestin-2-(1-380), but not of its caspase-resistant mutant,
      restores cell sensitivity to apoptotic stimuli. Arrestin-2-(1-380) action depends
      on tBID: at physiological concentrations, arrestin-2-(1-380) directly binds tBID
      and doubles tBID-induced cytochrome C release from isolated mitochondria.
      Arrestin-2-(1-380) does not facilitate apoptosis in BID knockout cells, whereas
      its ability to increase caspase-3 activity and facilitate cytochrome C release is
      rescued when BID expression is restored. Thus, arrestin-2-(1-380) cooperates with
      another product of caspase activity, tBID, and their concerted action
      significantly contributes to cell death. 

PMID- 24141719
TI  - Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes
      apoptosis and neurocristopathies in mice.
AB  - Neural crest cells (NCCs) migrate from different regions along the anterior
      posterior axis of the neural tube (NT) to form different structures. Defective
      NCC development causes congenital neurocristopathies affecting multiple NCC
      derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric
      nervous system (ENS) defects. This study aims to further investigate if perturbed
      Hoxb5 signaling in trunk NCC contributes to defects of other NCC-derived tissues
      besides the ENS. We perturbed Hoxb5 signaling in NCC from the entire NT, and
      investigated its impact in the development of tissues derived from these cells in
      mice. Perturbation of Hoxb5 signaling in these NCC resulted in Sox9
      downregulation, NCC apoptosis, hypoplastic sympathetic and dorsal root ganglia,
      hypopigmentation and ENS defects. Mutant mice with NCC-specific Sox9 deletion
      also displayed some of these phenotypes. In vitro and in vivo assays indicated
      that the Sox9 promoter was bound and trans-activated by Hoxb5. In ovo studies
      further revealed that Sox9 alleviated apoptosis induced by perturbed Hoxb5
      signaling, and Hoxb5 induced ectopic Sox9 expression in chick NT. This study
      demonstrates that Hoxb5 regulates Sox9 expression in NCC and disruption of this
      signaling causes Sox9 downregulation, NCC apoptosis and multiple NCC
      developmental defects. Phenotypes such as ENS deficiency, hypopigmentation and
      some of the neurological defects are reported in patients with Hirschsprung
      disease (HSCR). Whether dysregulation of Hoxb5 signaling and early depletion of
      NCC contribute to ENS defect and other neurocristopathies in HSCR patients
      deserves further investigation. 

PMID- 24141721
TI  - miR-661 downregulates both Mdm2 and Mdm4 to activate p53.
AB  - The p53 pathway is pivotal in tumor suppression. Cellular p53 activity is subject
      to tight regulation, in which the two related proteins Mdm2 and Mdm4 have major
      roles. The delicate interplay between the levels of Mdm2, Mdm4 and p53 is crucial
      for maintaining proper cellular homeostasis. microRNAs (miRNAs) are short non
      coding RNAs that downregulate the level and translatability of specific target
      mRNAs. We report that miR-661, a primate-specific miRNA, can target both Mdm2 and
      Mdm4 mRNA in a cell type-dependent manner. miR-661 interacts with Mdm2 and Mdm4
      RNA within living cells. The inhibitory effect of miR-661 is more prevalent on
      Mdm2 than on Mdm4. Interestingly, the predicted miR-661 targets in both mRNAs
      reside mainly within Alu elements, suggesting a primate-specific mechanism for
      regulatory diversification during evolution. Downregulation of Mdm2 and Mdm4 by
      miR-661 augments p53 activity and inhibits cell cycle progression in p53
      proficient cells. Correspondingly, low miR-661 expression correlates with bad
      outcome in breast cancers that typically express wild-type p53. In contrast, the
      miR-661 locus tends to be amplified in tumors harboring p53 mutations, and miR
      661 promotes migration of cells derived from such tumors. Thus, miR-661 may
      either suppress or promote cancer aggressiveness, depending on p53 status. 

PMID- 24141720
TI  - Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of
      human hematopoietic progenitors.
AB  - MicroRNAs (miRNAs) regulate cell proliferation, differentiation and death during
      development and postnatal life. The expression level of mature miRNAs results
      from complex molecular mechanisms, including the transcriptional regulation of
      their genes. MiR-223 is a hematopoietic-specific miRNA participating in
      regulatory signaling networks involving lineage-specific transcription factors
      (TFs). However, the transcriptional mechanisms governing its expression levels
      and its functional role in lineage fate decision of human hematopoietic
      progenitors (HPCs) have not yet been clarified. We found that in CD34(+)HPCs
      undergoing unilineage differentiation/maturation, miR-223 is upregulated more
      than 10-fold during granulopoiesis, 3-fold during monocytopoiesis and maintained
      at low levels during erythropoiesis. Chromatin immunoprecipitation and promoter
      luciferase assays showed that the lineage-specific expression level of mature miR
      223 is controlled by the coordinated binding of TFs to their DNA-responsive
      elements located in 'distal' and 'proximal' regulatory regions of the miR-223
      gene, differentially regulating the transcription of two primary transcripts (pri
      miRs). All this drives myeloid progenitor maturation into specific lineages.
      Accordingly, modulation of miR-223 activity in CD34(+)HPCs and myeloid cell lines
      significantly affects their differentiation/maturation into erythroid,
      granulocytic and monocytic/macrophagic lineages. MiR-223 overexpression increases
      granulopoiesis and impairs erythroid and monocytic/macrophagic differentiation.
      Its knockdown, meanwhile, impairs granulopoiesis and facilitates erythropoiesis
      and monocytic/macrophagic differentiation. Overall, our data reveal that
      transcriptional pathways acting on the differential regulation of two pri-miR
      transcripts results in the fine-tuning of a single mature miRNA expression level,
      which dictates the lineage fate decision of hematopoietic myeloid progenitors. 

PMID- 24141722
TI  - p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN.
AB  - PTEN is one of the most frequently mutated or deleted tumor suppressors in human
      cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN;
      however, a number of important questions remain regarding the role of
      ubiquitination in regulating PTEN function and the mechanisms by which PTEN
      ubiquitination is regulated. In the present study, we demonstrated that p34,
      which was identified as a binding partner of NEDD4-1, controls PTEN
      ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the
      WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression
      of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation,
      whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse
      correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples
      from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic
      behavior of NEDD4-1 and PTEN. 

PMID- 24141723
TI  - Eutectic melting in metal borohydrides.
AB  - A series of monometallic borohydrides and borohydride eutectic mixtures have been
      investigated during thermal ramping by mass spectroscopy, differential scanning
      calorimetry, and photography. Mixtures of LiBH4-NaBH4, LiBH4-KBH4, LiBH4
      Mg(BH4)2, LiBH4-Ca(BH4)2, LiBH4-Mn(BH4)2, NaBH4-KBH4, and LiBH4-NaBH4-KBH4 all
      displayed melting behaviour below that of the monometallic phases (up to 167 
      degrees C lower). Generally, each system behaves differently with respect to
      their physical behaviour upon melting. The molten phases can exhibit colour
      changes, bubbling and in some cases frothing, or even liquid-solid phase
      transitions during hydrogen release. Remarkably, the eutectic melt can also allow
      for hydrogen release at temperatures lower than that of the individual
      components. Some systems display decomposition of the borohydride in the solid
      state before melting and certain hydrogen release events have also been linked to
      the adverse reaction of samples with impurities, usually within the starting
      reagents, and these may also be coupled with bubbling or frothing of the ionic
      melt. 

PMID- 24141724
TI  - Short communication: sclerosing meningioma in the deep sylvian fissure.
AB  - Sclerosing meningioma is a rare type of meningeal tumor with extensive collagen
      depositions. Deep sylvian meningioma, a tumor that is unattached to the dura
      mater, is also unusual. The biological activity of both is controversial, as are
      therapeutic strategies. A heterogeneous contrast-enhanced mass in the right
      sylvian fissure of a 10-year-old boy with a 3-year history of epilepsy was
      identified via magnetic resonance imaging. The patient underwent partial surgical
      resection because the tumor was hard and contained numerous perforators arising
      from the right middle cerebral artery. The tumor was histologically diagnosed as
      sclerosing meningioma. Twelve months after surgery, the patient was asymptomatic
      and did not require any additional therapies. This case is the first report of a
      sclerosing meningioma arising in the deep sylvian fissure. We discuss the
      therapeutic dilemma of this case with respect to the current literature. 

PMID- 24141726
TI  - Acid-base responsive switching between "3+1" and "2+2" platinum complexes.
AB  - We report that the acid-base induced changes to a cyclometallated platinum
      complex can be used to drive the exchange of accompanying ligands with different
      denticities. 

PMID- 24141725
TI  - Collective identity and well-being of Bulgarian Roma adolescents and their
      mothers.
AB  - In Europe and specifically in Bulgaria, Roma represent the largest indigenous
      ethnic minority exposed to severe discrimination, social exclusion, poverty, and
      compromised well-being. To improve their conditions, identifying sources of
      psychological well-being for Roma is theoretically relevant and practically
      important. This study investigated the relation between ethnic, familial, and
      religious identities as salient collective identity components for psychological
      well-being among 194 Roma adolescents (age: M = 16.11 years, SD = 1.36) and their
      mothers (age: M = 35.95 years, SD = 3.54). The results indicated that in line
      with marginalization models of acculturation, Roma youth and their mothers showed
      a low endorsement of both Bulgarian mainstream and Roma ethnic identity. The
      average scores of well-being were also low. For both groups, familial identity
      was stronger compared to Roma, Bulgarian, and religious identity. A path model
      showed that collective identity was a positive predictor of well-being in both
      adolescents and mothers and that the mothers' collective identity was a predictor
      of adolescent well-being. Bulgarian mainstream identity had the strongest
      relationship with collective identity. It is concluded that, for Roma youth and
      their mothers, family is an important identity domain as it represents the most
      salient identification source that is not challenged in their environment.

PMID- 24141727
TI  - Realgar induces apoptosis in the chronic lymphocytic leukemia cell line MEC-1.
AB  - The aim of the present study was to investigate the effect of realgar on the
      viability, proliferation and apoptosis in the human chronic lymphocytic leukemia
      (CLL) cell line, MEC-1. Potential mechanisms mediating the effect were also
      explored in the experiment. Cultured MEC-1 cells were incubated with various
      concentrations of realgar for 24, 48 and 72 h. A WST-8 assay was employed to
      evaluate the effect on cell viability. Inhibitory effects on cell proliferation
      were determined using a 5-bromodeoxyuridine cell proliferation ELISA. The
      apoptotic effect on MEC-1 cells was evaluated by annexin V-fluorescein
      isothiocyanate/propidium iodide dual staining, followed by flow cytometry.
      Quantitative polymerase chain reaction was performed to determine the mRNA
      expression levels of BCL2-associated X protein (BAX), BCL2-like 1 (Bcl-xL), v-myc
      myelocytomatosis viral oncogene homolog (avian; c-Myc) and cyclin-dependent
      kinase inhibitor 1A (p21). It was found that viability and proliferation were
      significantly reduced while apoptotic rates increased in MEC-1 cells following
      exposure to realgar. Furthermore, mRNA expression of BAX and c-Myc was
      upregulated and downregulated, respectively, in realgar-treated MEC-1 cells. In
      conclusion, the results showed that realgar inhibits viability and prolife-ration
      and induces apoptosis of MEC-1 cells in a dose- and time-dependent manner. The
      effect may depend on the mitochondrial apoptosis pathway. The results of the
      present study may be beneficial in the identification of a new target therapy for
      CLL.

PMID- 24141729
TI  - Papilloedema is an independent prognostic factor for POEMS syndrome.
AB  - POEMS syndrome is a potentially fatal disease, and prediction of prognostic
      factors for POEMS syndrome is important for clinicians. Papilloedema is an early
      sign of the syndrome. The present study was carried out to evaluate whether
      papilloedema is a prognostic factor for POEMS syndrome. Between January 2003 and
      December 2012, 94 patients with POEMS syndrome were enrolled in this study. The
      patients were divided into groups with and without papilloedema. Logistic
      regression was performed to identify risk factors related to papilloedema.
      Prognostic factors were analysed with Cox proportional hazard regressions for
      POEMS syndrome-related prognoses, and survival curves were plotted using the
      Kaplan-Meier method and compared by the log-rank test. Papilloedema was found in
      52.1 % of the patients with POEMS syndrome. Raised intracranial pressure [hazard
      ratio (HR) 3.06, 95 % confidence interval (CI) 1.24-7.41; P = 0.011] and elevated
      cerebrospinal fluid protein levels (HR 2.03, 95 % CI 1.07-4.51; P = 0.043) were
      independently associated with papilloedema. Papilloedema, decreased diffusing
      capacity of the lung for carbon monoxide (DLCO) and treatment with
      corticosteroids alone were related to poor prognosis in POEMS syndrome. In
      multivariate analysis, papilloedema (HR 1.58, 95 % CI 1.05-2.46; p = 0.027) and
      decreased DLCO (HR 2.17, 95 % CI 1.12-3.39; p = 0.023) were independent factors
      for POEMS syndrome-related death. Papilloedema and decreased DLCO are important
      prognostic factors for patients with POEMS syndrome, which can help clinicians
      predict the risk of mortality and provide better medical care for these patients.

PMID- 24141730
TI  - Inverse eye position dependency of downbeat nystagmus in midline medullary
      lesion.

PMID- 24141731
TI  - Communications of the European Neurological Society.

PMID- 24141732
TI  - The high prevalence of hereditary spastic paraplegia in Sardinia, insular Italy.
AB  - The few epidemiological studies conducted to date on the heterogeneous group of
      hereditary spastic paraplegias (HSPs) indicate a prevalence of 1.27-12.1 per
      100,000. This study aims to explore the epidemiological, clinical, and genetic
      variability of HSPs among Sardinians, a population of peculiar ethnicity.A
      population-based prevalence study was performed in north-western Sardinia between
      January 2000 and December 2010. Multiple sources were used for case
      ascertainment. Familial and sporadic cases were diagnosed according to generally
      accepted criteria, and clinical diagnoses were validated by expert neurological
      examination. Clinical data and pedigree information were recorded and blood
      samples drawn for genetic testing.Sixty-seven HSP patients were included in the
      study: 59 belonged to 11 families with autosomal dominant transmission (AD-HSP),
      three cases were from two unrelated autosomal recessive families, and the
      remaining five cases were apparently sporadic. On 31 December 2010, the total
      crude prevalence was 19.9 per 100,000 (95 % CI 18.4-21.4), while the crude
      prevalence of AD-HSP was 17.5 (24.4 M, 15.7 F; M:F ratio 1.55). The mean age at
      examination was 48.4 years, and the mean age at onset of HSP was 36.6 years. A
      molecular diagnosis was obtained in 82.1 % of the cases (52 cases with mutations
      in SPAST/SPG4, two in SPG7, and one in SPG11).The prevalence of HSP among
      Sardinians is high compared with other Western European populations. The multiple
      search strategy used in this study and the specific socio-demographic
      characteristics of Sardinians may account for this finding.

PMID- 24141733
TI  - Myelin damage due to local quantitative abnormalities in normal prion levels:
      evidence from subacute combined degeneration and multiple sclerosis.
AB  - Cobalamin (Cbl) deficiency causes an imbalance in some cytokines and growth
      factors in the central nervous system and peripheral nervous system (PNS) of the
      rat, and in the serum and cerebrospinal fluid (CSF) of adult Cbl-deficient (Cbl
      D) patients. It is conceivable that this imbalance triggers subsequent cellular
      events. We hypothesized that an imbalance in normal prion (PrP(C)) levels and/or
      synthesis might be involved in the pathogenesis of Cbl-D neuropathy, and
      demonstrated that: (1) Cbl deficiency induces excess PrP(C) in rat spinal cord
      (SC) and PNS, concomitantly with myelin damage and PNS electrophysiological
      abnormalities; (2) the SC increase is mediated by a local Cbl deficiency-induced
      excess of tumor necrosis factor-alpha; (3) myelinotrophic Cbl and epidermal
      growth factor upregulate PrP(C)-mRNA levels in rat SC; (4) treatment with anti
      PrP(C) octapeptide repeat region antibodies normalizes the ultrastructure of the
      Cbl-D rat SC and PNS myelins, and the PNS electrophysiological abnormalities,
      without modifying their Cbl-D status; (5) PrP(C) administration to otherwise
      normal rats causes SC and PNS myelin lesions and PNS electrophysiological
      abnormalities, similar to those of Cbl-D neuropathy; (6) CSF and serum PrP(C)
      concentrations in Cbl-D patients are significantly higher than in controls; and
      (7) these concentrations significantly correlate with their CSF and serum Cbl
      concentrations. CSF PrP(C) concentrations are significantly lower in patients
      with multiple sclerosis (MS) than neurological controls, but serum PrP(C)
      concentrations in patients with non-Cbl-D anemias and CSF PrP(C) concentrations
      in patients with non-myelin-damaging neurological diseases are normal. 

PMID- 24141734
TI  - Safety of IV thrombolysis in an acute stroke patient anticoagulated with
      unfractioned heparin.

PMID- 24141735
TI  - Epigenetics of Huntington's disease.

PMID- 24141736
TI  - Next-generation sequencing of pharmacogenes: a critical analysis focusing on
      schizophrenia treatment.
AB  - INTRODUCTION: Because of the unmet needs of current pharmacotherapy for
      schizophrenia, antipsychotic pharmacogenetic research is of utmost importance.
      However, to date, few clinically applicable antipsychotic pharmacogenomic alleles
      have been identified. Nonetheless, next-generation sequencing technologies are
      expected to aid in the identification of clinically significant variants for this
      complex phenotype. The aim of this study was therefore to critically examine the
      ability of next-generation sequencing technologies to reliably detect variation
      present in pharmacogenes. MATERIALS AND METHODS: Candidate antipsychotic
      pharmacogenes and very important pharmacogenes were identified from the
      literature and the Pharmacogenomics Knowledgebase. Thereafter, the percentage
      sequence similarity observed between these genes and their corresponding
      pseudogenes and paralogues, as well as the percentage low-complexity sequence and
      GC content of each gene, was calculated. These sequence attributes were
      subsequently compared with the 'inaccessible' regions of these genes as described
      by the 1000 Genomes Project. RESULTS: It was found that the percentage
      'inaccessible genome' correlated well with GC content (P=9.96*10), low-complexity
      sequence (P=0.0002) and the presence of pseudogenes/paralogues (P=8.02*10). In
      addition, it was found that many of the pharmacogenes were not ideally suited to
      next-generation sequencing because of these genomic complexities. These included
      the CYP and HLA genes, both of which are of importance to many fields of
      pharmacogenetics. CONCLUSION: Current short read sequencing technologies are
      unable to comprehensively capture the variation in all pharmacogenes. Therefore,
      until high-throughput sequencing technologies advance further, it may be
      necessary to combine next-generation sequencing with other genotyping strategies.

PMID- 24141737
TI  - Olive oil mill wastewater for remediation of slag contaminated soil.
AB  - Two olive mill wastewaters (OMW) samples, OMWa and OMWb, containing different
      polyphenolic loads were used for decontaminating an unauthorized dump site in the
      Campania region, south Italy. In a bench-scale experiment, OMWa at pH 6.0
      (OMWapH6.0) and 4.7 (OMWapH4.7), OMWb at pH 4.7 (OMWbpH4.7) and OMWa free of the
      polyphenolic moiety polyphenol-free OMWa (PF-OMWa) were added to the soil for a
      96 h contact time. At 96 h, OMWapH4.7 was more effective than OMWapH6.0, with Cd,
      Cu, Pb and Zn removal percentages of 30.7-68.1. Cd and Pb levels were 6.0 and 915
      mg kg(-1), respectively, decreasing below the regulatory limits for industrial
      and commercial areas (15.0 and 1 * 10(3) mg kg(-1), respectively). A threefold
      decrease in Zn levels was also observed from 13.5 * 10(3) to 4.3 * 10(3) mg kg(
      1). The metal removal efficiency of PF-OMWa dropped from 30.7 % to 15.6 % for Cd
      and from 37.9 % to 1.3 % for Pb. OMWbpH4.7 at 96 h was more efficient than
      OMWapH4.7, with mean removal percentages of 32.5 versus 7.8, respectively. 

PMID- 24141738
TI  - Bubble-driven mixer integrated with a microfluidic bead-based ELISA for rapid
      bladder cancer biomarker detection.
AB  - In this study, fine bubbles were successfully generated and used as a simple, low
      cost driving force for mixing fluids in an integrated microfluidic bead-based
      enzyme-linked immunosorbent assay (ELISA) to rapidly and quantitatively detect
      apolipoprotein A1 (APOA1), a biomarker highly correlated with bladder cancer. A
      wooden gas diffuser was embedded underneath a microfluidic chip to refine
      injected air and generate bubbles of less than 0.3 mm. The rising bubbles caused
      disturbances and convection in the fluid, increasing the probability of analyte
      interaction. This setup not only simplifies the micromixer design but also
      achieves rapid mixing with a small airflow as a force. We used this bubble-driven
      micromixer in a bead-based ELISA that targeted APOA1. The results indicate that
      this micromixer reduced the time for each incubation from 60 min in the
      conventional assay to 8 min with the chip, resulting in a reduction of total
      ELISA reaction time from 3-4 h to 30-40 min. Furthermore, the concentration
      detection limit was 9.16 ng/mL, which was lower than the detection cut-off value
      (11.16 ng/mL) for bladder cancer diagnosis reported in the literature. Therefore,
      this chip can be used to achieve rapid low-cost bladder cancer detection and may
      be used in point-of-care cancer monitoring. 

PMID- 24141739
TI  - Amphiphilic ferrocenylated alkylpyridinium: the formation of micelles and
      hydrogels and their disaggregation induced by an external stimulus.
AB  - Ferrocene-containing amphiphiles [py-N-(CH2)nOCH2Fc]Cl (n = 6 (1a), 8 (1b), 10
      (1c); py = C5H5N, Fc = Fe(C5H4)(C5H5)) were synthesized. The absorption spectra
      of 1a-1c in the presence of a small amount of dye (Nile red and pyrene) in
      aqueous media suggested the formation of micelles which encapsulated the dye
      molecules. Two critical micelle concentrations were observed at 1.1 mM and 2.3 mM
      at 20  degrees C. Compounds 1a and 1c showed a single CMC for each, while the
      formation of two kinds of micelles, the spherical and rod-like ones, depended on
      the concentrations. The addition of an oxidant, NaOCl, to the aqueous solution of
      the micelles of 1b turned ferrocene to ferrocenium and caused the disaggregation
      of the micelles. The addition of alpha-cyclodextrin (alpha-CD) to 2b caused the
      disaggregation of the micelle and the formation of water-soluble [2]- and
      [3]pseudorotaxane [{py-N-(CH2)8OCH2Fc}(alpha-CD)m]Cl (1b(alpha-CD)m) (m = 1, 2),
      while mixing 1c and alpha-CD in water formed the rotaxane gel. The addition of
      NaOCl to the hydrogel of 1c and alpha-CD changed the gel to sol. 

PMID- 24141740
TI  - Ultrahigh-field imaging of the biliary tract at 7 T: initial results of gadoxetic
      acid-enhanced magnetic resonance cholangiography.
AB  - OBJECTIVES: The objectives of this study were to assess the feasibility of
      magnetic resonance cholangiography (MRC) using biliary-secreted gadoxetic acid at
      7 T and to compare it with T2-weighted (w) MRC at 3 T. MATERIALS AND METHODS: Ten
      healthy volunteers were examined on a 7-T whole-body magnetic resonance system.
      T2-weighted turbo-spin-echo sequence, T1-w volume-interpolated breath-hold
      examination (VIBE), and fast low-angle shot (FLASH) with inversion recovery (IR)
      were acquired in coronal orientation. For dynamic imaging, gadoxetic acid was
      administrated and data were collected for a period of 5 to 40 minutes after
      injection. The volunteers underwent subsequent T2-w respiratory-gated MRC at 3 T.
      For qualitative analysis, a 5-point scale was used. Contrast ratios (CRs) were
      calculated for quantitative assessment. RESULTS: Contrast-enhanced T1-w MRC at 7
      T showed a homogeneous depiction of the intrahepatic and extrahepatic biliary
      tract with a maximum enhancement of 20 minutes after contrast. Volume
      interpolated breath-hold examination and FLASH IR provided a good image quality
      for the intrahepatic (VIBE, 3.60; FLASH IR, 3.67) and extrahepatic bile ducts
      (VIBE, 3.50; FLASH IR, 3.72). The quantitative analysis revealed high CR values
      for FLASH IR (intrahepatic CR, 0.41; extrahepatic CR, 0.45) because of an
      effective suppression of hepatic tissue and vessels. The T2-w TSE at 7 T showed
      only a poor image quality without diagnostic potential (intrahepatic, 2.22;
      extrahepatic, 1.93). Seven-tesla VIBE and FLASH revealed superiority in the
      depiction of the intrahepatic bile ducts, whereas 3-T MRC was superior in the
      delineation of the extrahepatic biliary tract. CONCLUSIONS: Our results
      demonstrate the feasibility of contrast-enhanced imaging of the biliary ducts at
      7 T.

PMID- 24141741
TI  - Feasibility of single-source dual-energy computed tomography for urinary stone
      characterization and value of iterative reconstructions.
AB  - PURPOSE: The purposes of this study were to demonstrate the feasibility and
      accuracy of single-source dual-energy (DE) computed tomography (CT) with
      sequential data acquisition and a coregistration motion correction algorithm for
      urinary stone characterization and to evaluate the value of iterative
      reconstructions (IRs) in DE imaging. MATERIALS AND METHODS: Thirty-five urinary
      stones were placed in cylindrical phantoms with diameters of 30 and 40 cm. The
      phantoms were scanned on a 64-section CT machine with a single-source DE protocol
      consisting of 2 sequential acquisitions at 80 and 140 kilovolt (peak). The
      phantom was moved between the 80- and 140-kilovolt (peak) scans. Images were
      reconstructed with weighted filtered back projection (FBP) and with IR, and data
      were coregistered. Two independent and blinded readers assessed data sets for
      stone detection, overall image quality, and visibility of stones. Image noise and
      Hounsfield unit values of the stones were measured, and the DE index was
      calculated. In addition, the data sets were analyzed on color-coded images using
      the standard postprocessing software for differentiating uric acid- (UA) from non
      UA-containing stones. RESULTS: The motion correction algorithm achieved a good
      coregistration of the 2 scans with different energy levels. Both readers detected
      all stones on all data sets with both reconstruction types. The overall image
      quality was rated significantly higher in IR images in the 40-cm phantom as
      compared with that in FBP images (P < 0.05), whereas no significant difference
      was found for the 30-cm phantom. Visibility of stones was rated significantly
      higher for both the 30- and 40-cm phantoms on IR as compared with that on FBP
      images, an effect that was pronounced for UA stones (P < 0.05). Noise was
      significantly reduced by up to 31% in the 40-cm phantom when using IR as compared
      with FBP (P < 0.001). The DE index was similar in the FBP and IR data sets for
      the 30- (P = 0.116) and 40-cm phantoms (P = 0.544), being significantly different
      between UA-containing stones, cystine, and struvite stones as well as stones of
      other compositions (P < 0.001). The postprocessing software classified all stones
      correctly as UA- or non-UA-containing stones on color-coded images. In the 40-cm
      phantom, false-positively colored voxels were found in the FBP data sets, which
      were not seen when using IR instead. CONCLUSIONS: Our study indicates that single
      source dual-energy CT with sequential acquisitions at different energy levels and
      a coregistration motion correction algorithm is feasible and accurate for
      characterizing urinary stone composition on the basis of phantom evaluation. As
      compared with reconstructions with FBP, the use of IR in dual-energy CT reduces
      noise, improves overall image quality and visibility of stones particularly in
      large phantoms, and helps to avoid false classifications of urinary stones.

PMID- 24141742
TI  - A study on mastectomy samples to evaluate breast imaging quality and potential
      clinical relevance of differential phase contrast mammography.
AB  - OBJECTIVES: Differential phase contrast and scattering-based x-ray mammography
      has the potential to provide additional and complementary clinically relevant
      information compared with absorption-based mammography. The purpose of our study
      was to provide a first statistical evaluation of the imaging capabilities of the
      new technique compared with digital absorption mammography. MATERIALS AND
      METHODS: We investigated non-fixed mastectomy samples of 33 patients with
      invasive breast cancer, using grating-based differential phase contrast
      mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We
      simultaneously recorded absorption, differential phase contrast, and small-angle
      scattering signals that were combined into novel high-frequency-enhanced images
      with a dedicated image fusion algorithm. Six international, expert breast
      radiologists evaluated clinical digital and experimental mammograms in a 2-part
      blinded, prospective independent reader study. The results were statistically
      analyzed in terms of image quality and clinical relevance. RESULTS: The results
      of the comparison of mammoDPC with clinical digital mammography revealed the
      general quality of the images to be significantly superior (P < 0.001);
      sharpness, lesion delineation, as well as the general visibility of
      calcifications to be significantly more assessable (P < 0.001); and delineation
      of anatomic components of the specimens (surface structures) to be significantly
      sharper (P < 0.001). Spiculations were significantly better identified, and the
      overall clinically relevant information provided by mammoDPC was judged to be
      superior (P < 0.001). CONCLUSIONS: Our results demonstrate that complementary
      information provided by phase and scattering enhanced mammograms obtained with
      the mammoDPC approach deliver images of generally superior quality. This
      technique has the potential to improve radiological breast diagnostics.

PMID- 24141743
TI  - Application of a unique test design to determine the chronic toxicity of boron to
      the aquatic worm Lumbriculus variegatus and fatmucket mussel Lampsilis
      siliquoidea.
AB  - The chronic (21- and 28-day) toxicity of boron was determined for two freshwater
      benthic macroinvertebrates: the fatmucket mussel Lampsilis siliquoidea and the
      aquatic worm Lumbriculus variegatus. The rapid depletion of boric acid from
      spiked sediments in tests using flow-through overlying waters was addressed by
      constant addition of boric acid to overlying water at concentrations matching
      those of the targeted porewater exposures. This proved highly successful in
      maintaining constant whole-sediment and sediment porewater boron concentrations.
      Boron sublethal 25 % inhibition concentration values based on porewater
      concentrations were 25.9 mg B/L (L. variegatus) and 38.5 mg B/L (L. siliquoidea),
      indicating similar test organism sensitivity. Expressed as dry whole-sediment
      values, the respective L. variegatus and L. siliquoidea sublethal (growth) IC25
      values for whole-sediment exposures were 235.5 mg B/kg sediment dry weight (dw)
      and 310.6 mg B/kg dw. The worm lethality-based end points indicated greater
      sensitivity than the sublethal end points, bringing into question the validity of
      a "lethality" end point for L. variegatus given its fragmentation mode of
      reproduction. For comparison, water-only mussel exposures were tested resulting
      in an IC25 value of 34.6 mg B/L, which was within 20 % of the porewater value.
      This suggests that the primary route of boron exposure was through the aqueous
      phase. The results of this study indicated that for test materials that are
      readily water soluble, standard sediment test designs may be unsuitable, but
      water-only exposures can provide toxicological data representative of sediment
      tests. 

PMID- 24141745
TI  - Correlation between inflammatory infiltrate and epithelial lining in 214 cases of
      periapical cysts.
AB  - The aim of this study was to evaluate the prevalence of periapical cysts,
      identify their clinical and microscopic features and correlate their microscopic
      features with the inflammatory infiltrate present in the lesion site. A total of
      214 cases were collected over a 10-year period. Clinical data, including gender,
      age, race, symptoms and location of the lesion, were recorded. Two independent
      examiners with no prior knowledge of the patients' clinical data conducted the
      microscopic evaluations. Statistical analyses were performed using Fisher's or
      chi-square tests at a 5% level of significance. The results showed that
      periapical cysts were more prevalent in white women, with a mean age of 35 years,
      and in the anterosuperior region. The majority of the lesions were lined by
      atrophic cystic epithelium, which was associated with moderate inflammatory
      infiltrate in the cystic capsule (p < 0.01), with a diffuse localization pattern
      (p = 0.03) and absence of neutrophils (p = 0.01). Our findings suggest that
      periapical cysts lined by atrophic epithelium are related to the presence of
      moderate mononuclear inflammatory infiltrate.

PMID- 24141746
TI  - Fathers' and mothers' ratings of behavioral and emotional problems in siblings of
      children with autism spectrum disorder.
AB  - Debate is ongoing about whether typically developing siblings of children with
      autism spectrum disorder (ASD) are at greater risk of behavioral or emotional
      problems than siblings of children without ASD. Most data on behavior is provided
      by mothers, and we do not know whether fathers' reports differ. The strengths and
      difficulties questionnaire (Goodman in J Child Psychol Psychiatry 38(5):581-586,
      1997) was completed by 168 mothers and 130 fathers. Parents were more likely to
      rate siblings as having 'abnormal' behavior when compared to a normative
      population. We found moderate correlations between mother-father ratings. More
      research may be needed to understand any clinical benefits of gathering data
      about sibling adjustment from more than one parent in the family. Implications
      for clinical practice and future research are discussed. 

PMID- 24141747
TI  - Exploring perceptual skills in children with autism spectrum disorders: from
      target detection to dynamic perceptual discrimination.
AB  - Perceptual processing in autism is associated with both 'strengths' and
      'weaknesses' but within a literature that varies widely in terms of the
      assessments used. We report data from 12 children with autism spectrum disorders
      (ASD) and 12 age and IQ matched neurotypical controls tested on a set of tasks
      using the same stimuli throughout but systematically changing in difficulty.
      These tasks ranged through simple detection of stimulus onset to pairwise size
      discrimination across two approaching targets. Children with ASD were slower than
      controls even in simple detection tasks, but this did not explain further group
      differences found in the size discrimination of approaching targets. The results
      are discussed in terms of impairments in speed of responding in ASD under certain
      conditions of visuomotor coupling, stimulus presentation and increased
      information processing demands. 

PMID- 24141749
TI  - Boosting supercapacitor performance of carbon fibres using electrochemically
      reduced graphene oxide additives.
AB  - Modifying conventional materials with new recipes represents a straightforward
      yet efficient way to realize large-scale applications of new materials.
      Electrochemically reduced graphene oxide (ERGO) coated carbon fibres (CFs),
      prepared as fibre-like supercapacitor electrodes, exhibited excellent
      electrochemical energy storage performance. Upon addition of only a small amount
      (~1 wt%) of ERGO, the hybrid fibres showed superior electrochemical capacitances
      (nearly three orders of magnitude enhanced) compared to pure CFs in both aqueous
      and gel electrolytes. Meanwhile, the energy density did not decrease notably as
      the power density increased. The superior capacitive performance could be
      attributed to the synergistic effect between wrinkled and porous ERGO sheets and
      highly conductive CFs. This fibre electrode material also offered advantages such
      as easy operation, mass production capability, mechanical flexibility and
      robustness, and could have an impact on a wide variety of potential applications
      in energy and electronic fields.

PMID- 24141748
TI  - The behavior of ligament cells cultured on elastin and collagen scaffolds.
AB  - The ruptured anterior cruciate ligament (ACL) does not heal spontaneously.
      Therefore, the development of new healing techniques employing tissue engineering
      is vital. One of the aspects related to tissue-engineered artificial ligaments is
      the type of cell to be used for the artificial ligament. In this study, ligament
      cells from the ACL and periodontal ligament (PDL) were evaluated. In addition, we
      prepared highly oriented extracellular matrix (ECM) fiber scaffolds that mimicked
      the structure of the ligament and examined the cellular responses to these
      scaffolds. Elastin-A and collagen were used as the ECM proteins. Although the
      cells from the PDL (PDL fibroblasts [PDLFs]) showed approximately 2.1-fold higher
      expression of alkaline phosphatase (ALP; marker of osteogenic differentiation)
      than the ACL cells, the expression of ligament-related genes (for type I
      collagen, type III collagen, and tenomodulin) did not differ between PDLFs and
      ACL cells. Furthermore, the cellular responses (expression pattern of ligament
      related genes and ALP activity) to the ECM were similar between ACL cells and
      PDLFs. In particular, elastin-A upregulated ALP and downregulated tenomodulin
      (TeM; a ligament marker) in ligament cells. In contrast, collagen maintained TeM
      expression in ligament cells. These results suggest that elastin-A promotes the
      osteogenic differentiation of ligament cells and that collagen maintains the
      phenotype of ligament cells. 

PMID- 24141750
TI  - Fusional amplitudes: exploring where fusion falters.
AB  - BACKGROUND AND PURPOSE: The stability of binocular vision depends on good
      fusional amplitudes, but the assessment of fusional amplitudes varies around the
      world. The author reviewed the literature on fusional amplitudes and surveyed
      international orthoptists on their assessment of fusional amplitudes. The purpose
      of the study was to determine whether or not there is variation in fusional
      amplitudes in normal subjects when looking at the role of examiner encouragement;
      the order of testing; the method of testing; and the subject's level of
      alertness. The preliminary results from this ongoing, prospective study are
      presented. PATIENTS AND METHODS: Using a modified crossover design study, the
      author prospectively assessed fusional amplitudes in fifty participants with
      normal eye exams who met inclusion criteria. The measurements were done in two
      separate sessions with each participant being randomized as to the order of
      fusional vergence testing. All participants were assessed without and with
      encouragement in the first session. In the second session, all were assessed at
      different testing distances. RESULTS: Convergence is significantly affected by
      encouragement and divergence is significantly reduced if assessed after
      convergence. Numbers were too small to get meaningful data on the effect of
      fatigue on final outcome measures. CONCLUSIONS: We need to develop consistency in
      assessing fusional amplitudes and agree upon a standard of testing. Variables
      such as the order of testing, whether or not encouragement is given, and a
      person's level of alertness can affect the final outcome. Encouragement should be
      done especially when assessing convergence fusional amplitudes and divergence
      should be assessed prior to convergence. Finally, it is important to note a
      patient's level of alertness during vergence testing, especially if they are
      feeling foggy on one visit and are alert on the next. By implementing these
      strategies into your assessment of fusional amplitudes, the examiner will know if
      a change in amplitudes is due to treatment effect or just testing method.

PMID- 24141751
TI  - Introduction.

PMID- 24141752
TI  - Beyond the cover test: the motor half of the sensorimotor exam.
AB  - The cover tests fulfill both the "sensory" and the "motor" requirements of the
      sensorimotor exam because they not only detect and quantify strabismus but also
      evaluate control. Control is achieved through various types of vergence, but
      vergence is not the only type of eye movement that is integral to fusion. The
      function of all eye movements is to position and maintain similar images on
      corresponding areas of the retinae in order to sustain binocular vision.
      Therefore, a complete motor exam should include evaluation of all eye movement
      systems. Such an exam can be performed without expensive and complicated
      equipment, without supplementary education, without significantly extending exam
      time, and within the confines of an average exam lane, because much of the exam
      is concealed within the standard sensorimotor evaluation. The term "sensorimotor
      exam" underscores the fact that sensory and motor fusion, and their respective
      cortical pathways, are inextricably linked, and function simultaneously and
      cooperatively to achieve normal visual experience. 

PMID- 24141753
TI  - Nonsurgical treatment of neurologic diplopia.
AB  - The ocular motor pathways are complex and disorders of these pathways can be
      devastating for patients, in some cases leading to loss of employment and
      independence. Surgical intervention for these cases is not always warranted,
      possible, or even safe for some patients, and nonsurgical and orthoptic
      treatments can provide significant relief. This paper will discuss various
      treatment options, including eye exercises, prisms, optical manipulation,
      occlusion, and lifestyle changes. 

PMID- 24141754
TI  - Surgical solutions for supranuclear and internuclear ocular motility problems.

PMID- 24141755
TI  - Efficacy of modified cover testing for detection of incipient true strabismus
      with pseudostrabismus diagnosis.
AB  - BACKGROUND AND PURPOSE: Retrospective studies have shown that as many as 15% of
      patients with pseudostrabismus go on to develop true strabismus. This prospective
      study was conducted to examine the efficacy of utilizing a modified cover test
      technique to help identify patients with pseudostrabismus that are likely to
      progress to true strabismus. PATIENTS AND METHODS: Fifty-three subjects were
      included in the study. All were evaluated using prolonged occlusion during cover
      testing ("occlusive" cover test). The results of this test were analyzed for its
      ability to predict the development of true strabismus during a mean follow-up
      period of 11 months. RESULTS: The occlusive cover test was of value in detecting
      which subjects would later develop esotropia. CONCLUSION: The occlusive cover
      test should be incorporated into the evaluation of patients suspected of having
      pseudostrabismus to identify which patients are most at risk of presenting later
      with true strabismus.

PMID- 24141756
TI  - Synostotic anterior plagiocephaly: a cause of familial congenital superior
      oblique muscle palsy.
AB  - Anterior plagiocephaly due to unicoronal craniosynostosis is commonly associated
      with an ipsilateral hypertropia and a contralateral head tilt. The ipsilateral
      superior oblique weakness has been attributed to the shortening of the orbital
      roof with retroplacement of the trochlea, and to heterotopic positioning of the
      vertical rectus muscles within the orbit. These anatomical aberrations may alter
      ocular rotations to mimic a true congenital superior oblique palsy. This paper
      describes two siblings with synostotic plagiocephaly and simulated superior
      oblique palsy with ocular torticollis successfully managed by strabismus surgery.
      Synostotic plagiocephaly should be included in the differential diagnosis of
      familial congenital superior oblique palsy. 

PMID- 24141757
TI  - Selection of patients and results of 25 years of topical anesthesia and
      adjustable suture surgery.
AB  - BACKGROUND AND PURPOSE: The author has used adjustable suture techniques either
      in the operating room with topical anesthesia or at a later time after
      retrobulbar or general anesthesia for over 25 years. Careful selection of
      patients is essential to the success of this technique. It is the purpose of this
      paper to report the selection criteria used and to compare the results of the two
      methods utilized. PATIENTS AND METHODS: One hundred eighty-three patients were
      included in this study: 123 were operated upon with topical anesthesia. For
      comparison, sixty patients were included who had adjustment later in the day or
      the next day after having retrobulbar or general anesthesia. Both horizontal and
      vertical strabismus cases were included. RESULTS: Adjustable techniques done in
      the operating room or at a later time have both shown significant improvement in
      the strabismus angle following one operation in 86% of the cases. Diplopia was
      eliminated in 63% of patients with this complaint. (63% and 64.5% in the two
      groups, respectively). Seventeen of 123 patients having topical anesthesia
      (13.8%) required a second operation, and 8 of 60 (13.3%) of those having a later
      adjustment needed further surgery. CONCLUSION: Careful selection of patients
      undergoing strabismus surgery allows successful topical muscle adjustment in the
      operating room with results similar to adjustments done following retrobulbar or
      general anesthesia at a later time.

PMID- 24141758
TI  - Socioeconomics of retinopathy of prematurity care in the United States.
AB  - BACKGROUND AND PURPOSE: To elucidate the experience of pediatric ophthalmologists
      across the United States who care for infants with retinopathy of prematurity
      (ROP). METHODS: Seven hundred and ten surveys were mailed to U.S. members of the
      American Association of Pediatric Ophthalmology and Strabismus, and 283 (40%) of
      710 surveys were completed. Surveys were reviewed and statistical analysis was
      completed by the authors. RESULTS: There was no uniformity of contract
      compensation or method for determining the value of ROP care. Almost half of the
      respondents felt they would generate more income if they did not perform ROP
      screening. Eighty percent of respondents that were happy with their ROP
      compensation had a contract for those services. One third of respondents had
      their malpractice insurance provided by the hospital. Retina specialists
      performed 40% of inpatient ROP screening and 53% of treatment. Most respondents
      continued to care for infants with ROP once discharged. CONCLUSIONS: In the
      United States, there is no uniform experience regarding compensation for ROP
      care, or a methodology for determining the value of services and coverage of
      liability insurance. These findings are consistent with previous studies. Lack of
      uniform compensation and high liability pose a threat to the future of ROP care.

PMID- 24141759
TI  - The Bruckner test variant (BTV): a promising instrument in detecting vision
      disorders.
AB  - BACKGROUND AND PURPOSE: In the Netherlands, children are screened for amblyopia
      based on the early detection of visual disorders (VOV) protocol by child health
      care physicians. The positive predictive value (PPV) of the Bruckner test variant
      (BTV) as an alternative method was assessed. PATIENTS AND METHODS: In this
      historical prospective analysis, the results of the VOV and BTV methods were
      compared. Results at the ages of 15 and 27 months of 414 children were compared
      against diagnosis by the ophthalmologist; follow-up was at 72 months. RESULTS:
      Visual disorders were found in 12 of 15 children (14 had an abnormal BTV) who
      underwent ophthalmological examination. The PPV of the BTV was 86%; 12 of the 14
      children with an abnormal BTV had a vision disorder in the preverbal phase.
      CONCLUSION: The BTV is superior to the VOV method in the early detection of
      vision disorders and could be a cost-effective public health intervention.

PMID- 24141760
TI  - Incidence of strabismus and amblyopia in preverbal children previously diagnosed
      with pseudoesotropia.
AB  - BACKGROUND AND PURPOSE: We previously reported that 12% of children under age 3
      diagnosed with pseudoesotropia without significant refractive error later
      developed strabismus or mild refractive amblyopia. Mohan and Sharma recently
      reported on fifty-one patients with pseudoesotropia and hyperopia and noted that
      esotropia developed in 53.9% of the children with >1.50 D of hypermetropia
      compared to 2.6% of those who had <=1.50 D hypermetropia, implying a low risk of
      esotropia unless hyperopia was greater than 1.50 D on initial exam. We reviewed
      our data to see if we had similar findings in our patients. METHOD: Medical
      records between January 1, 2001, and February 26, 2010, were reviewed
      retrospectively. Three hundred ninety-four patients diagnosed with
      pseudoesotropia with an otherwise normal examination were reviewed, and 253 with
      follow-up were analyzed. RESULTS: Forty-six children were 36 months or older at
      initial presentation; none developed strabismus; 207 children were <36 months at
      initial presentation; twenty-two children (11%) were later found to have
      strabismus. Seventy-eight of these children had hyperopia > 1.50 D; eight
      children (10%) later developed strabismus. One hundred twenty-nine children had
      hyperopia <= 1.50 D, and fourteen (11%) developed strabismus. Our analysis showed
      an equal risk of strabismus developing in pseudoesotropia patients under age 3
      with greater or less than 1.50 D of hyperopia. CONCLUSION: There is a significant
      risk of esotropia developing in children under three diagnosed with
      pseudoesotropia. Hyperopia less than 1.50 D, does not obviate the need for
      careful follow-up.

PMID- 24141761
TI  - Osteopetrosis.
AB  - Osteopetrosis is a rare disease that occurs when a child has an unequal balance
      between new bone growth and elimination of old bone. Children with this entity
      are able to make new bone tissue, but are not able to break down and eliminate
      old bones, which is essential for normal bone growth. These thickened and
      enlarged bones are very weak. These children can exhibit: failure to thrive,
      macrocephaly, anemia, deafness, and blindness. We will present a case of
      osteopetrosis, esotropia, and amblyopia of a 7-year-old boy and will discuss the
      pathophysiology and treatment. 

PMID- 24141762
TI  - Historical vignette: Walter Brackett Lancaster (1863-1951): surgeon, educator,
      and promoter of orthoptics.

PMID- 24141767
TI  - Rearrangement and expression of the immunoglobulin MU-chain gene in human myeloid
      cells.
AB  - Immunoglobulin (Ig), a characteristic marker of B cells, has been reported to be
      expressed in epithelial cells, with a suggested role in their growth and
      survival. We have previously reported that IgG heavy chain is expressed in acute
      myeloid leukemia (AML), but not in the monocytes or neutrophils from patients
      with non-hematopoietic neoplasms or healthy controls. In the present study, we
      assessed IgM heavy chain expression and repertoire in human myeloid cells. We
      detected VHMUDJHMU rearrangement and expression in 7/7 AML cell lines, 7/14
      primary myeloblasts from AML patients, and interestingly, 8/20 monocytes and 3/20
      neutrophils from patients with non-hematopoietic neoplasms and healthy
      individuals. We also found evidence of somatic hypermutation of the variable (V)
      gene segments in AML-derived IgM gene rearrangements but not in IgM from
      monocytes or neutrophils from patients with non-hematopoietic neoplasms and
      healthy individuals. Furthermore, IgM VHMUDJHMU gene rearrangements in AML cell
      lines, primary myeloblasts, and monocytes and neutrophils from patients with non
      hematopoietic neoplasms showed a restricted V usage and repertoire, whereas the
      VHMUDJHMU gene rearrangements in monocytes and neutrophils from healthy
      individuals displayed more diversity. Anti-human IgM inhibited cell
      proliferation, but did not induce apoptosis in AML cell lines. Our findings
      suggest that AML-derived IgM might be a novel AML-related molecule that is
      involved in leukemogenesis and AML progression and might serve as a useful
      molecular marker for designing targeted therapy and monitoring minimal residual
      disease. 

PMID- 24141768
TI  - A modified murine model based on hydrodynamic injection for the analysis of
      chronic human hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) is a persistent pathogen that causes acute and chronic
      necroinflammatory liver disease and is attributable to ~1 million deaths per
      year. In the present study, a conventional murine model was introduced based on
      the hydrodynamic injection of engineered replication-competent HBV DNA into the
      tail veins of C57BL/6 mice. In a previous study, nine in-frame ATG (start) codons
      in the S open reading frame (S1-S9) were analyzed. The highly conserved ATG S5
      was mutated to ACG by T378C, which led to the substitution sM75T and inhibition
      of the production and secretion of the hepatitis B surface antigen (HBsAg), and
      subsequent inhibition of HBV replication. In the present study, T378C was
      introduced into the pAAV-HBV1.3 plasmid and was confirmed to affect HBsAg
      production and secretion, and HBV replication in vivo, which was in agreement
      with the previous in vitro results. Furthermore, the murine model was improved by
      co-injection of the replication-competent HBV plasmid DNA with Lipofectamine 2000
      (LP). In this model, LP not only significantly enhanced HBV replication in mice,
      but also upregulated the expression of HBsAg and the hepatitis B core antigen.
      The current modified murine model was superior to the conventional murine HBV
      model based on HBV challenge by hydrodynamic injection.

PMID- 24141769
TI  - A functional interaction of E7 with B-Myb-MuvB complex promotes acute cooperative
      transcriptional activation of both S- and M-phase genes. (129 c).
AB  - High-risk human papillomaviruses are causative agents of cervical cancer. Viral
      protein E7 is required to establish and maintain the pro-oncogenic phenotype in
      infected cells, but the molecular mechanisms by which E7 promotes carcinogenesis
      are only partially understood. Our transcriptome analyses in primary human
      fibroblasts transduced with the viral protein revealed that E7 activates a group
      of mitotic genes via the activator B-Myb-MuvB complex. We show that E7 interacts
      with the B-Myb, FoxM1 and LIN9 components of this activator complex, leading to
      cooperative transcriptional activation of mitotic genes in primary cells and E7
      recruitment to the corresponding promoters. E7 interaction with LIN9 and FoxM1
      depended on the LXCXE motif, which is also required for pocket protein
      interaction and degradation. Using E7 mutants for the degradation of pocket
      proteins but intact for the LXCXE motif, we demonstrate that E7 functional
      interaction with the B-Myb-MuvB complex and pocket protein degradation are two
      discrete functions of the viral protein that cooperate to promote acute
      transcriptional activation of mitotic genes. Transcriptional level of E7 in
      patient's cervical lesions at different stages of progression was shown to
      correlate with those of B-Myb and FoxM1 as well as other mitotic gene
      transcripts, thereby linking E7 with cellular proliferation and progression in
      cervical cancer in vivo. E7 thus can directly activate the transcriptional levels
      of cell cycle genes independently of pocket protein stability. 

PMID- 24141770
TI  - PTEN functions as a melanoma tumor suppressor by promoting host immune response.
AB  - Cancer cells acquire several traits that allow for their survival and
      progression, including the ability to evade the host immune response. However,
      the mechanisms by which cancer cells evade host immune responses remain largely
      elusive. Here we study the phenomena of immune evasion in malignant melanoma
      cells. We find that the tumor suppressor phosphatase and tensin homolog (PTEN) is
      an important regulator of the host immune response against melanoma cells.
      Mechanistically, PTEN represses the expression of immunosuppressive cytokines by
      blocking the phosphatidylinositide 3-kinase (PI3K) pathway. In melanoma cells
      lacking PTEN, signal transducer and activator of transcription 3 activates the
      transcription of immunosuppressive cytokines in a PI3K-dependent manner.
      Furthermore, conditioned media from PTEN-deficient, patient-derived short-term
      melanoma cultures and established melanoma cell lines blocked the production of
      the interleukin-12 (IL-12) in human monocyte-derived dendritic cells. Inhibition
      of IL-12 production was rescued by restoring PTEN or using neutralizing
      antibodies against the immunosuppressive cytokines. Furthermore, we report that
      PTEN, as an alternative mechanism to promote the host immune response against
      cancer cells, represses the expression of programmed cell death 1 ligand, a known
      repressor of the host immune response. Finally, to establish the clinical
      significance of our results, we analyzed malignant melanoma patient samples with
      or without brisk host responses. These analyses confirmed that PTEN loss is
      associated with a higher percentage of malignant melanoma samples with non-brisk
      host responses compared with samples with brisk host responses. Collectively,
      these results establish that PTEN functions as a melanoma tumor suppressor in
      part by regulating the host immune response against melanoma cells and highlight
      the importance of assessing PTEN status before recruiting melanoma patients for
      immunotherapies. 

PMID- 24141771
TI  - A reciprocal role of prostate cancer on stromal DNA damage.
AB  - DNA damage found in prostate cancer-associated fibroblasts (CAF) promotes tumor
      progression. In the absence of somatic mutations in CAF, epigenetic changes
      dictate how stromal coevolution is mediated in tumors. Seventy percent of
      prostate cancer patients lose expression of transforming growth factor-beta type
      II receptor (TGFBR2) in the stromal compartment (n=77, P-value=0.0001), similar
      to the rate of glutathione S-transferase P1 (GSTP1) silencing. Xenografting of
      human prostate cancer epithelia, LNCaP, resulted in the epigenetic Tgfbr2
      silencing of host mouse prostatic fibroblasts. Stromal Tgfbr2 promoter
      hypermethylation, initiated by LNCaP cells, was found to be dependent on
      interleukin 6 expression, based on neutralizing antibody studies. We further
      found that pharmacologic and transgenic knockout of TGF-beta responsiveness in
      prostatic fibroblasts induced Gstp1 promoter methylation. It is known that TGF
      beta promotes DNA stability, however, the mechanism is not well understood. Both
      prostatic human CAF and mouse transgenic knockout of Tgbr2 had elevated DNA
      methyltransferase I (DNMT1) activity and histone H3 lysine 9 trimethylation
      (H3K9me3) to suggest greater promoter methylation. Interestingly, the conditional
      knockout of Tgfbr2 in mouse prostatic fibroblasts, in modeling epigenetic
      silencing of Tgfbr2, had greater epigenetic gene silencing of multiple DNA damage
      repair and oxidative stress response genes, based on promoter methylation array
      analysis. Homologous gene silencing was validated by reverse transcriptase (RT)
      PCR in mouse and human prostatic CAF. Not surprisingly, DNA damage repair gene
      silencing in the prostatic stromal cells corresponded with the presence of DNA
      damage. Restoring the expression of the epigenetically silenced genes in wild
      type fibroblasts with radiation-induced DNA damage reduced tumor progression.
      Tumor progression was inhibited even when epigenetic silencing was reversed in
      the Tgfbr2-knockout prostatic fibroblasts. Taken together, fibroblastic
      epigenetic changes causative of DNA damage, initiated by association with cancer
      epithelia, is a dominant mediator of tumor progression over TGF-beta
      responsiveness. 

PMID- 24141772
TI  - HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to
      cytosolic/extracellular pH gradient regulation by the vacuolar-H(+) ATPase.
AB  - Haeme-responsive gene (HRG)-1 encodes a 16-kDa transmembrane protein that is
      induced by insulin-like growth factor-1 (IGF-1) and associates with the vacuolar
      (H(+)) ATPase (V-ATPase). We previously reported that HRG-1 is essential for V
      ATPase activity in endosomal acidification and receptor trafficking. Here, we
      show that in highly invasive and migratory cancer cell lines, HRG-1 and the V
      ATPase are co-expressed at the plasma membrane, whereas in less invasive cell
      lines and non-transformed cells HRG-1 over-expression remains confined to
      intracellular compartments. Stable suppression of HRG-1 in invasive breast cancer
      MDA-MB-231 cells decreases extracellular pH, cell growth, migration and invasion.
      Ectopic expression of HRG-1 in non-invasive MCF-7 cells enhances V-ATPase
      activity, lowers the extracellular pH and increases the pH-dependent activity of
      MMP2 and MMP9 matrix metalloproteinases. HRG-1 enhances trafficking of the
      glucose transporter-1 (GLUT-1) with a concomitant increase in glucose uptake and
      lactate production. HRG-1 also promotes trafficking of the insulin-like growth
      factor I receptor (IGF-1R), beta1-integrin and IGF-1 signalling. Taken together,
      our findings indicate that HRG-1 expression at the plasma membrane enhances V
      ATPase activity, drives glycolytic flux and facilitates cancer cell growth,
      migration and invasion. Thus, HRG-1 may represent a novel target for selectively
      disrupting V-ATPase activity and the metastatic potential of cancer cells. 

PMID- 24141773
TI  - DRR regulates AKT activation to drive brain cancer invasion.
AB  - Glioblastoma (GBM) is the most common and invasive adult brain cancer. The rapid
      invasion of cancer cells into the normal brain is a major cause of treatment
      failure, yet the mechanisms that regulate this process are poorly understood. We
      have identified a novel mechanism of brain cancer invasion. We show that
      downregulated in renal cell carcinoma (DRR), which is newly expressed in invasive
      gliomas, recruits AKT to focal adhesions. This DRR- induced pathological
      relocalization of AKT bypasses commonly altered upstream signaling events and
      leads to AKT activation and invasion. We also developed an oligonucleotide
      therapeutic that reduces DRR expression and prevents glioma invasion in an in
      vivo preclinical model of the disease. Our findings identify DRR as a novel GBM
      target and show that oligonucleotides targeting DRR is a novel therapeutic
      approach for the treatment of DRR-positive GBMs. 

PMID- 24141774
TI  - Immunosuppressive networks and checkpoints controlling antitumor immunity and
      their blockade in the development of cancer immunotherapeutics and vaccines.
AB  - Vaccines that promote protective adaptive immune responses have been successfully
      developed against a range of infectious diseases, and these are normally
      administered prior to exposure with the relevant virus or bacteria. Adaptive
      immunity also plays a critical role in the control of tumors. Immunotherapeutics
      and vaccines that promote effector T cell responses have the potential to
      eliminate tumors when used in a therapeutic setting. However, the induction of
      protective antitumor immunity is compromised by innate immunosuppressive
      mechanisms and regulatory cells that often dominate the tumor microenvironment.
      Recent studies have shown that blocking these suppressor cells and immune
      checkpoints to allow induction of antitumor immunity is a successful
      immunotherapeutic modality for the treatment of cancer. Furthermore, stimulation
      of innate and consequently adaptive immune responses with concomitant inhibition
      of immune suppression, especially that mediated by regulatory T (Treg) cells, is
      emerging as a promising approach to enhance the efficacy of therapeutic vaccines
      against cancer. This review describes the immunosuppressive mechanisms
      controlling antitumor immunity and the novel strategies being employed to design
      effective immunotherapeutics against tumors based on inhibition of suppressor
      cells or blockade of immune checkpoints to allow induction of more potent
      effector T cell responses. This review also discusses the potential of using a
      combination of adjuvants with inhibition of immune checkpoint or suppressor cells
      for therapeutic vaccines and the translation of pre-clinical studies to the next
      generation vaccines against cancer in humans. 

PMID- 24141775
TI  - GRP78 as a regulator of liver steatosis and cancer progression mediated by loss
      of the tumor suppressor PTEN.
AB  - Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in
      human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress
      signaling and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that
      GRP78 maintains homeostasis of metabolic organs, including liver, pancreas and
      adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are
      the most common liver cancers. There is a lack of effective therapeutics for HCC
      and CC, highlighting the need to further understand liver tumorigenic mechanisms.
      PTEN (phosphatase and tenson homolog deleted on chromosome 10), a tumor
      suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range
      of tumors, including 40-50% of human liver cancers. To elucidate the role of
      GRP78 in liver cancer, we created a mouse model with biallelic liver-specific
      deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cP(f/f)78(f/f)).
      Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but
      incomplete. At 3 months, cP(f/f)78(f/f) livers showed hepatomegaly, activation of
      lipogenic genes, exacerbated steatosis and liver injury, implying that GRP78
      protects the liver against PTEN-null-mediated pathogenesis. Furthermore, in
      response to liver injury, we observed increased proliferation and expansion of
      bile duct and liver progenitor cells in cP(f/f)78(f/f) livers. Strikingly, bile
      duct cells in cP(f/f)78(f/f) livers maintained wild-type (WT) GRP78 level,
      whereas adjacent areas showed GRP78 reduction. Analysis of signaling pathways
      revealed selective JNK activation, beta-catenin downregulation, along with
      PDGFRalpha upregulation, which was unique to cP(f/f)78(f/f) livers at 6 months.
      Development of both HCC and CC was accelerated and was evident in cP(f/f)78(f/f)
      livers at 8-9 months, coinciding with intense GRP78 expression in the cancer
      lesions, and GRP78 expression in adjacent normal areas reverted back to the WT
      level. In contrast, c78(f/f) livers showed no malignancy even at 14 months. These
      studies reveal that GRP78 is a novel regulator for PTEN-loss-mediated liver
      injury and cancer progression. 

PMID- 24141777
TI  - The age- and shorter telomere-dependent TERT promoter mutation in follicular
      thyroid cell-derived carcinomas.
AB  - Telomerase activation through induction of its catalytic component telomerase
      reverse transcriptase (TERT) expression is essential for malignant
      transformation. TERT promoter mutations namely C228T and C250T that stimulate
      TERT transcription and telomerase activation have recently been identified in
      many human malignancies. We thus determined these mutations and their biological
      and clinical implications in thyroid carcinomas in the present study. The TERT
      promoter was sequenced in 10 thyroid cancer cell lines and 144 tumors from 20
      patients with anaplastic thyroid carcinoma (ATC), 51 with papillary thyroid
      carcinoma (PTC), 36 with follicular thyroid carcinoma (FTC), and 37 with
      medullary thyroid carcinoma (MTC). We identified C228T or C250T mutation in 6/8
      of ATC cell lines, as well as in tumor tissue from 10/20, 13/51, 8/36 and 0/37
      patients with ATC, PTC, FTC and MTC, respectively. In PTC patients, these
      mutations were exclusively present in the group with age >45 years (P<0.0001),
      and highly correlated shorter telomeres (P<0.0001) and distant metastasis
      (P=0.028). The previous radioactivity exposure did not induce the mutation. The
      presence of C228T or C250T was an independent predictor associated with shorter
      disease-related survival (DRS) in the entire cohort (P<0.0001), as well as among
      patients >45 years (P=0.021). ATC patients carrying the mutation survived shorter
      than those without mutations, although not statistically significant (P=0.129).
      The TERT promoter mutation was associated with overall survival (P=0.038) and DRS
      (P=0.058) of FTC patients. Taken together, age- and shorter telomere-dependent
      TERT promoter mutations occur frequently in follicular cell-derived thyroid
      carcinoma (ATC, PTC and FTC) but not in parafollicular cell-originated MTC, and
      may serve as a marker for aggressive disease and poor outcome. 

PMID- 24141776
TI  - Effects on tumor development and metastatic dissemination by the NKG2D lymphocyte
      receptor expressed on cancer cells.
AB  - The stimulatory NKG2D lymphocyte receptor together with its tumor-associated
      ligands enable the immune system to recognize and destroy cancer cells. However,
      with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune
      evasion and suppression. Recent findings have added yet another functional
      dimension, wherein cancer cells themselves co-opt NKG2D for their own benefit to
      complement the presence of its ligands for self-stimulation of parameters of
      tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing
      by employing orthotopic xenotransplant breast cancer models in mice. Using human
      cancer lines with ectopic NKG2D expression and RNA interference (RNAi)-mediated
      protein depletion among other controls, we show that NKG2D self-stimulation has
      tumor-promoting capacity. NKG2D signals had no notable effects on cancer cell
      proliferation and survival but acted at the level of angiogenesis, thus promoting
      tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects
      on tumor initiation may represent another factor in the observed overall
      enhancement of tumor development. Altogether, these results may have an impact on
      immunotherapy approaches, which currently do not account for such NKG2D effects
      in cancer patients and thus could be misdirected as underlying assumptions are
      incomplete. 

PMID- 24141778
TI  - Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced
      silencing complex.
AB  - Oncogene MYC is highly expressed in many human cancers and functions as a global
      regulator of ribosome biogenesis. Previously, we reported that ribosomal protein
      (RP) L11 binds to c-Myc and inhibits its transcriptional activity in response to
      ribosomal stress. Here, we show that RPL5, co-operatively with RPL11, guides the
      RNA-induced silencing complex (RISC) to c-Myc mRNA and mediates the degradation
      of the mRNA, consequently leading to inhibition of c-Myc activity. Knocking down
      of RPL5 induced c-Myc expression at both mRNA and protein levels, whereas
      overexpression of RPL5 suppressed c-Myc expression and activity.
      Immunoprecipitation revealed that RPL5 binds to 3'UTR of c-Myc mRNA and two
      subunits of RISC, TRBP (HIV-1 TAR RNA-binding protein) and Ago2, mediating the
      targeting of c-Myc mRNA by miRNAs. Interestingly, RPL5 and RPL11 co-resided on c
      Myc mRNA and suppressed c-Myc expression co-operatively. These findings uncover a
      mechanism by which these two RPs can co-operatively suppress c-Myc expression,
      allowing a tightly controlled ribosome biogenesis in cells. 

PMID- 24141779
TI  - Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like
      breast cancer and engineering of interference peptides block its oncogenic
      function.
AB  - Basal-like breast tumors are aggressive cancers associated with high
      proliferation and metastasis. Chemotherapy is currently the only treatment
      option; however, resistance often occurs resulting in recurrence and patient
      death. Some extremely aggressive cancers are also associated with hypoxia,
      inflammation and high leukocyte infiltration. Herein, we discovered that the
      neural-specific transcription factor, Engrailed 1 (EN1), is exclusively
      overexpressed in these tumors. Short hairpin RNA (shRNA)-mediated knockdown of
      EN1 triggered potent and selective cell death. In contrast, ectopic
      overexpression of EN1 in normal cells activated survival pathways and conferred
      resistance to chemotherapeutic agents. Exogenous expression of EN1 cDNA
      reprogrammed the breast epithelial cells toward a long-lived, neural-like
      phenotype displaying dopaminergic markers. Gene expression microarrays
      demonstrated that the EN1 cDNA altered transcription of a high number of
      inflammatory molecules, notably chemokines and chemokine receptors, which could
      mediate prosurvival pathways. To block EN1 function, we engineered synthetic
      interference peptides (iPeps) comprising the EN1-specific sequences that mediate
      essential protein-protein interactions necessary for EN1 function and an N
      terminal cell-penetrating peptide/nuclear localization sequence. These EN1-iPeps
      rapidly mediated a strong apoptotic response in tumor cells overexpressing EN1,
      with no toxicity to normal or non EN1-expressing cells. Delivery of EN1-iPeps
      into basal-like cancer cells significantly decreased the fifty percent inhibitory
      concentrations (IC50) of chemotherapeutic drugs routinely used to treat breast
      cancer. Lastly, matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry and immunoprecipitation assays demonstrated that EN1-iPeps captured
      targets involved in transcriptional and post-transcriptional regulation.
      Importantly, the EN1-iPeps bound the glutamyl-prolyl tRNA synthetase (EPRS)
      target, which has been associated with the transcript-specific translational
      control of inflammatory proteins and activation of amino-acid stress pathways.
      This work unveils EN1 as an activator of intrinsic inflammatory pathways
      associated with prosurvival in basal-like breast cancer. We further build upon
      these results and describe the engineering of iPeps targeting EN1 (EN1-iPeps) as
      a novel and selective therapeutic strategy to combat these lethal forms of breast
      cancer.

PMID- 24141780
TI  - RSK2 regulates endocytosis of FGF receptor 1 by phosphorylation on serine 789.
AB  - FGFR1 (fibroblast growth factor receptor 1) regulates many key cellular responses
      including proliferation, migration and differentiation through activation of
      signaling pathways. Irregularities in FGFR1 signaling have been implicated in
      several pathological conditions, including human cancer. In order to discover
      novel regulators of FGFR1 signaling, we performed yeast two-hybrid screens and
      identified RSK2 (p90 ribosomal S6 kinase 2) as a potential FGFR1 interaction
      partner. RSK2 belongs to the family of serine/threonine kinases that are
      activated through the Ras-MAPK signal transduction pathway. Both in vitro and in
      vivo experiments confirmed the interaction and we show that phosphorylated RSK2
      binds to and phosphorylates serine 789 in the C-terminal tail of FGFR1.
      Inhibition of RSK2 activity led to prolonged tyrosine transphosphorylation of
      FGFR1. Furthermore, prevention of FGFR1 phosphorylation by inhibition of RSK2
      activity or mutation of serine 789 to alanine reduced FGFR1 endocytosis and
      ubiquitination explaining mechanistically the prolonged signaling activity. We
      propose a novel regulatory mechanism whereby activated RSK2 directly interacts
      with and phosphorylates FGFR1, thereby modulating receptor signaling through
      regulation of endocytosis. 

PMID- 24141782
TI  - Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal
      development.
AB  - MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However,
      its mammary physiological function remains largely unknown. In the present study
      we have investigated MMP-11 function during postnatal mammary gland development
      and function using MMP-11-deficient (MMP-11-/-) mice. Histological and
      immunohistochemical analyses as well as whole-mount mammary gland staining show
      alteration of the mammary gland in the absence of MMP-11, where ductal tree,
      alveolar structures and milk production are reduced. Moreover, a series of
      transplantation experiments allowed us to demonstrate that MMP-11 exerts an
      essential local paracrine function that favors mammary gland branching and
      epithelial cell outgrowth and invasion through adjacent connective tissues.
      Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium
      development, whereas MMP-11-/- epithelium transplants grow normally when
      implanted in wild-type cleared fat pads. In addition, using primary mammary
      epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is
      not direct, suggesting that MMP-11 acts via production/release of stroma
      associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased
      periductal collagen content, suggesting that MMP-11 has a role in collagen
      homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial
      cell behavior mechanically by promoting extracellular matrix stiffness.
      Collectively, the present data indicate that MMP-11 is a paracrine factor
      involved during postnatal mammary gland morphogenesis, and support the concept
      that the stroma strongly impact epithelial cell behavior. Interestingly, stromal
      MMP-11 has previously been reported to favor malignant epithelial cell survival
      and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during
      mammary gland development that might be harnessed to promote tumor progression,
      exposing a new link between development and malignancy. 

PMID- 24141781
TI  - Identification of latent biomarkers in hepatocellular carcinoma by ultra-deep
      whole-transcriptome sequencing.
AB  - There is an urgent need to identify biomarkers for hepatocellular carcinoma due
      to limited treatment options and the poor prognosis of this common lethal
      disease. Whole-transcriptome shotgun sequencing (RNA-Seq) provides new
      possibilities for biomarker identification. We sequenced ~250 million pair-end
      reads from a pair of adjacent normal and tumor liver samples. With the aid of
      bioinformatics tools, we determined the transcriptome landscape and sought novel
      biomarkers by further empirical validations in 55 pairs of adjacent normal and
      tumor liver samples with various viral statuses such as HBV(+), HCV(+) and HBV(
      )HCV(-). We identified a novel gene with coding regions, termed DUNQU1, which has
      a tissue-specific expression pattern in tumor liver samples of HCV(+) and HBV(
      )HCV(-) hepatocellular carcinomas. Overexpression of DUNQU1 in Huh7 cell lines
      enhances the ability to form colonies in soft agar. Also, we identified three
      novel differentially-expressed protein-coding genes (ALG1L, SERPINA11 and TMEM82)
      that lack documented expression profiles in liver cancer and showed that the
      level of SREPINA11 is correlated with pathology stages. Moreover, we showed that
      the alternative splicing event of FGFR2 is associated with virus infection, tumor
      size, cirrhosis and tumor recurrence. The findings indicate that these new
      markers of hepatocellular carcinoma may be of value in improving prognosis and
      could have potential as new targets for developing new treatment options.

PMID- 24141783
TI  - Hedgehog signaling induces osteosarcoma development through Yap1 and H19
      overexpression.
AB  - Osteosarcoma is one of the most common bone tumors. However, the genetic basis
      for its pathogenesis remains elusive. Here, we investigated the roles of Hedgehog
      (Hh) signaling in osteosarcoma development. Genetically-engineered mice with
      ubiquitous upregulated Hh signaling specifically in mature osteoblasts develop
      focal bone overgrowth, which greatly resembles the early stage of osteosarcoma.
      However, these mice die within three months, which prohibits further analysis of
      tumor progression. We therefore generated a mouse model with partial upregulated
      Hh signaling in mature osteoblasts and crossed it into a p53 heterozygous
      background to potentiate tumor development. We found that these mutant mice
      developed malignant osteosarcoma with high penetrance. Isolated primary tumor
      cells were mainly osteoblastic and highly proliferative with many characteristics
      of human osteosarcomas. Allograft transplantation into immunocompromised mice
      displayed high tumorigenic potential. More importantly, both human and mouse
      tumor tissues express high level of yes-associated protein 1 (Yap1), a potent
      oncogene that is amplified in various cancers. We show that inhibition of Hh
      signaling reduces Yap1 expression and knockdown of Yap1 significantly inhibits
      tumor progression. Moreover, long non-coding RNA H19 is aberrantly expressed and
      induced by upregulated Hh signaling and Yap1 overexpression. Our results
      demonstrate that aberrant Hh signaling in mature osteoblasts is responsible for
      the pathogenesis of osteoblastic osteosarcoma through Yap1 and H19
      overexpression. 

PMID- 24141784
TI  - Context-dependent adaption of EpCAM expression in early systemic esophageal
      cancer.
AB  - The role of the epithelial cell adhesion molecule EpCAM in cancer progression
      remains largely unclear. High expression of EpCAM in primary tumors is often
      associated with more aggressive phenotypes and EpCAM is the prime epithelial
      antigen in use to isolate circulating tumor cells (CTCs) and characterize
      disseminated tumor cells (DTCs). However, reduced expression of EpCAM was
      associated with epithelial-to-mesenchymal transition (EMT) and reports on a lack
      of EpCAM on CTCs emerged. These contradictory observations might reflect a
      context-dependent adaption of EpCAM expression during metastatic progression. To
      test this, EpCAM expression was monitored in esophageal cancer at different sites
      of early systemic disease. Although most of the primary esophageal tumors
      expressed high levels of EpCAM, the majority of DTCs in bone marrow lacked EpCAM.
      In vitro, downregulation of EpCAM expression at the plasma membrane was observed
      in migrating and invading cells, and was associated with a partial loss of the
      epithelial phenotype and with significantly decreased proliferation. Accordingly,
      induction of EMT through the action of TGFbeta resulted in substantial loss of
      EpCAM cell surface expression on esophageal cancer cells. Knock-down or natural
      loss of EpCAM recapitulated these effects as it reduced proliferation while
      enhancing migration and invasion of cancer cells. Importantly, expression of
      EpCAM on DTCs was significantly associated with the occurrence of lymph node
      metastases and with significantly decreased overall survival of esophageal cancer
      patients. We validated this observation by showing that high expression of EpCAM
      promoted tumor outgrowth after xenotransplantation of esophageal carcinoma cells.
      The present data disclose a dynamic expression of EpCAM throughout tumor
      progression, where EpCAM(high) phenotypes correlate with proliferative stages,
      whereas EpCAM(low/negative) phenotypes associated with migration, invasion and
      dissemination. Thus, differing expression levels of EpCAM must be taken into
      consideration for therapeutic approaches and during clinical retrieval of
      disseminated tumor cells. 

PMID- 24141785
TI  - MicroRNA-9 inhibits the proliferation of oral squamous cell carcinoma cells by
      suppressing expression of CXCR4 via the Wnt/beta-catenin signaling pathway.
AB  - Aberrant expression of microRNAs (miRNAs) has been involved in the development
      and progression of malignancy. MicroRNA-9 (miR-9) has been confirmed to be
      underexpressed in many types of cancers. However, the relationship between miR-9
      and the Wnt/beta-catenin signaling pathway in oral squamous cell carcinoma (OSCC)
      remains largely unknown. Here we showed that the miR-9 was underexpressed in
      patients with OSCC and several OSCC cell lines. Lentivirus-mediated miR-9
      overexpression in highly aggressive (Tca8113 and SCC-9) tumor cells significantly
      inhibited proliferation of the two cell lines in vitro and in vivo. Furthermore,
      we found that the CXC chemokine receptor 4 (CXCR4) gene was a direct target of
      miR-9. RNA interference silencing of CXCR4 proved that miR-9 underexpression led
      to constitutive activation of beta-catenin through activation of CXCR4 expression
      in OSCC cells. Finally, we also analyzed the possible relationship between miR-9
      and the genes downstream of the Wnt/beta-catenin pathway in OSCC development and
      progression. These results provide new evidence of miR-9 as a promising tumor
      gene therapeutic target for OSCC patients. 

PMID- 24141786
TI  - Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations.
AB  - Uveal melanoma (UM) is a genetically and biologically distinct type of melanoma,
      and once metastatic there is no effective treatment currently available. Eighty
      percent of UMs harbor mutations in the Galphaq family members GNAQ and GNA11.
      Understanding the effector pathways downstream of these oncoproteins is important
      to identify opportunities for targeted therapy. We report consistent activation
      of the protein kinase C (PKC) and MAPK pathways as a consequence of GNAQ or GNA11
      mutation. PKC inhibition with AEB071 or AHT956 suppressed PKC and MAPK signalling
      and induced G1 arrest selectively in melanoma cell lines carrying GNAQ or GNA11
      mutations. In contrast, treatment with two different MEK inhibitors, PD0325901
      and MEK162, inhibited the proliferation of melanoma cell lines irrespective of
      their mutation status, indicating that in the context of GNAQ or GNA11 mutation
      MAPK activation can be attributed to activated PKC. AEB071 significantly slowed
      the growth of tumors in an allograft model of GNAQ(Q209L)-transduced melanocytes,
      but did not induce tumor shrinkage. In vivo and in vitro studies showed that PKC
      inhibitors alone were unable to induce sustained suppression of MAP-kinase
      signaling. However, combinations of PKC and MEK inhibition, using either
      PD0325901or MEK162, led to sustained MAP-kinase pathway inhibition and showed a
      strong synergistic effect in halting proliferation and in inducing apoptosis in
      vitro. Furthermore, combining PKC and MEK inhibition was efficacious in vivo,
      causing marked tumor regression in a UM xenograft model. Our data identify PKC as
      a rational therapeutic target for melanoma patients with GNAQ or GNA11 mutations
      and demonstrate that combined MEK and PKC inhibition is synergistic, with
      superior efficacy compared to treatment with either approach alone.

PMID- 24141787
TI  - Breast cancer-associated missense mutants of the PALB2 WD40 domain, which
      directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.
AB  - Heterozygous carriers of germ-line mutations in the BRCA2/FANCD1, PALB2/FANCN and
      RAD51C/FANCO DNA repair genes have an increased lifetime risk of developing
      breast, ovarian and other cancers; bi-allelic mutations in these genes clinically
      manifest as Fanconi anemia (FA). Here, we demonstrate that RAD51C is part of a
      novel protein complex that contains PALB2 and BRCA2. Further, the PALB2 WD40
      domain can directly and independently bind RAD51C and BRCA2. To understand the
      role of these homologous recombination (HR) proteins in DNA repair, we
      functionally characterize effects of missense mutants of the PALB2 WD40 domain
      that have been reported in breast cancer patients. In contrast to large
      truncations of PALB2, which display a complete loss of interaction, the L939W,
      T1030I and L1143P missense mutants/variants of the PALB2 WD40 domain are
      associated with altered patterns of direct binding to the RAD51C, RAD51 and BRCA2
      HR proteins in biochemical assays. Further, the T1030I missense mutant is
      unstable, whereas the L939W and L1143P proteins are stable but partially disrupt
      the PALB2-RAD51C-BRCA2 complex in cells. Functionally, the L939W and L1143P
      mutants display a decreased capacity for DNA double-strand break-induced HR and
      an increased cellular sensitivity to ionizing radiation. As further evidence for
      the functional importance of the HR complex, RAD51C mutants that are associated
      with cancer susceptibility and FA also display decreased complex formation with
      PALB2. Together, our results suggest that three different cancer susceptibility
      and FA proteins function in a DNA repair pathway based upon the PALB2 WD40 domain
      binding to RAD51C and BRCA2.